PMID- 18607595
TI  - Long-term survival after sequential chemoradiation for limited disease small cell
      carcinoma of the bladder.
AB  - OBJECTIVES: To evaluate response, time to progression and survival of patients
      with limited disease (LD) small cell carcinoma of the bladder (SCCB) treated with
      sequential chemoradiation in analogy to LD small cell lung cancer (SCLC).
      METHODS: Of 42 patients with SCCB treated at our institution between 1993 and
      2007, 17 with LD SCCB treated with chemoradiation were identified and
      retrospectively analysed. LD was defined as any pT, cN0-1, cM0. SCCB was defined
      according to WHO criteria. All patients had platinum-based chemotherapy after
      transurethral resection (TUR) prior to local radiotherapy with 56-70 Gy. RESULTS:
      Sixteen patients were male, 1 female. Median age was 62 years. Median overall
      survival is 32.5 months. All had a clinical local response (15 CR, 2 PR).
      Systemic progression occurred in 8 (47%) with a median time to progression of 6
      months (range 1-16 months), 8 died with a median survival of 17.5 months.
      Currently, 7 are free of disease (FOD) including 2 at 80 and 87 months. Four
      (23.5%) had a local recurrence as late as 43 and 50 months; 3 required a salvage
      cystectomy. CONCLUSIONS: Clinical results of sequential chemoradiation for LD
      SCCB are comparable to contemporary series of LD SCCB treated with cystectomy and
      upfront or adjuvant chemotherapy. Long-term survival of more than 5 years after
      chemoradiation can be achieved. The risk of local recurrence is lower than
      reported, but late recurrences occur. These data suggest that bladder sparing
      with systemic chemotherapy and local control by radiotherapy should be further
      investigated in this aggressive disease.

PMID- 18607596
TI  - The nitric oxide pathway in the human prostate: clinical implications in men with
      lower urinary tract symptoms.
AB  - To date, there is an increasing interest in the nitric oxide (NO) pathway as a
      potential pharmacological target to treat male lower urinary tract symptomatology
      (LUTS). In the transition zone of the human prostate, a dense nitrinergic
      innervation has been shown of the fibromuscular stroma, glandular epithelium and
      blood vessels. The expression of key proteins of the NO pathway, such as the
      endothelial and neuronal nitric oxide synthase (eNOS, nNOS), cGMP-degrading
      phosphodiesterase type 5 (PDE5) and cGMP-binding protein kinase (cGK), has also
      been demonstrated. The hypothesis that an impaired NO/cGMP-signaling may
      contribute to the pathophysiology of benign prostatic hyperplasia (BPH) is
      supported by the results from randomized, placebo-controlled clinical studies,
      indicating that NO donor drugs and PDE5-inhibitors sildenafil, tadalafil and
      vardenafil may be useful to treat storage and voiding dysfunctions resulting from
      LUTS in men. Thus, given a potential role of the NO-pathway in the prostate
      and/or in other parts of lower urinary tract (e.g. bladder), the enhancement of
      the NO signaling by NO donor drugs, PDE5 inhibitors or activators of the soluble
      guanylyl cyclase (sGC) may represent a new therapeutic strategy for the treatment
      of LUTS. This review serves to focus on the role of NO and the NO-dependent
      signaling in the control of smooth muscle function in the human prostate. Results
      from clinical trials in men with LUTS/BPH are also discussed.

PMID- 18607598
TI  - Erythropoietin producing cells for potential cell therapy.
AB  - INTRODUCTION: Anemia is an inevitable outcome of chronic renal failure due to the
      kidney's decreased ability to produce erythropoietin (EPO). We examined the
      feasibility of isolating and expanding EPO-producing cells for cell-based
      therapy. MATERIALS AND METHODS: Renal cells from 7- to 10-day-old mice were
      culture-expanded. The cells at each subculture stage were characterized for EPO
      expression, using immunocytochemistry, FACS, and Western Blot analysis, with EPO
      specific antibodies. To assess the levels of EPO expression, cells incubated
      under normoxic and hypoxic conditions were analyzed. RESULTS: Immunocytochemical
      analysis of the cultured renal cells expressed EPO at each subculture stage (P1
      P3). Western Blot analysis of the detergent-solubilized cell extracts detected
      EPO (34 kDa) protein in the kidney cells of all passages tested. CONCLUSION:
      These results demonstrate that EPO-producing renal cells can be grown and
      expanded in culture. The cells stably expressed EPO at multiple subculture stages
      and they are able to form tissue in vivo. This study shows that EPO-producing
      cells may be used as a potential treatment option for anemia caused by chronic
      renal failure.

PMID- 18607599
TI  - An alternative continence tube for continent urinary reservoirs: evaluation of
      surgical technique, pressure and continence study in an ex-vivo model.
AB  - OBJECTIVE: Despite the large number of surgical techniques for continent
      cutaneous diversion described in literature, the creation of a reliable,
      continent and easily catheterizable continence mechanism remains a complex
      surgical procedure. AIM: Aim of this study was the evaluation of a new method for
      a catheterizable continence mechanism using stapled pig intestine. METHODS: Small
      and large pig intestines were used for construction. A 3 or 6 cm double row
      stapling system was used. Three variations using small and large intestine
      segments were constructed. A 3 or 6 cm long stapler line was placed alongside a
      12 Fr catheter positioned at the antimesenterial side creating a partially two
      luminal segment. Construction time for the tube was measured. The created tube
      was then embedded into the pouch. Pressure evaluation of the continence mechanism
      was performed for each variation. Intermittent external manual compression was
      used to simulate sudden pressure exposure. RESULTS: All variations were 100%
      continent under filling volumes of up to 700 ml and pressure levels of 58 +/- 6
      cm H(2)O for large intestine and 266 ml and 87 +/- 18 cm H(2)O for small
      intestine, respectively. With further filling above the mentioned capacity suture
      insufficiency occurred but no tube insufficiency. Construction time for all
      variations was less than 12 min. CONCLUSION: The described technique is an easy
      and fast method to construct a continence mechanism using small or large
      intestine. Our ex vivo experiments have shown sufficient continence situation in
      an ex-vivo model. Further investigations in an in-vivo model are needed to
      confirm these results.

PMID- 18607597
TI  - Penile cancer: epidemiology, pathogenesis and prevention.
AB  - OBJECTIVES: Penile cancer is a disease with a high morbidity and mortality. Its
      prevalence is relatively rare, but the highest in some developing countries.
      Insight into its precursor lesions, pathogenesis and risk factors offers options
      to prevent this potentially mutilating disease. This review presents an overview
      of the different histologically and clinically identified precursor lesions of
      penile cancer and discusses the molecular pathogenesis, including the role of HPV
      in penile cancer development. METHODS: A systematic review of the literature
      evaluating penile carcinogenesis, risk factors and molecular mechanisms involved.
      RESULTS: Careful monitoring of men with lichen sclerosis, genital Bowen's
      disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby
      offering early recognition of penile cancer and, subsequently, conservative
      therapeutic options. Special attention is given to flat penile lesions, which
      contain high numbers of HPV. Their role in HPV transmission to sexual partners is
      highlighted, but their potential to transform as a precursor lesion into penile
      cancer has been unsatisfactorily explored. CONCLUSIONS: Further research should
      not only focus on HPV mediated pathogenic pathways but also on the non-HPV
      related molecular and genetic factors that play a role in penile cancer
      development. Options for prevention of penile cancer include (neonatal)
      circumcision, limitation of penile HPV infections (either by prophylactic
      vaccination or condom use), prevention of phimosis, treatment of chronic
      inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic
      measures.

PMID- 18607600
TI  - [Introduction to the topic: quality of life in ophthalmology].

PMID- 18607601
TI  - [Anti-VEGF treatment for retinal angiomatous proliferation].
AB  - BACKGROUND: Retinal angiomatous proliferation (RAP) is a subform of neovascular
      age-related macular degeneration (AMD), which is characterized by a particularly
      poor prognosis. The aim of this study is to describe the loading phase and
      maintenance phase for RAP during intravitreal anti-VEGF treatment. MATERIAL AND
      METHODS: A total of 82 eyes in 82 patients with RAP stages 1-3 were treated
      during upload therapy with repeated intravitreal injections of 1.25 mg
      bevacizumab at intervals of 4 weeks until the retinal edema resolved. Baseline
      examination included measurement of the best corrected distance visual acuity
      (ETDRS chart), central retinal thickness using optical coherence tomography
      (OCT), and fluorescein angiography (FLA). During maintenance therapy, the
      patients' distance visual acuity was monitored at 4- to 12-week intervals and OCT
      or FLA performed if needed. The average follow-up was 7.4 months (SD 4.2).
      Treatment with intravitreal anti-VEGF therapy was repeated if there was evidence
      of sub- or intraretinal fluid with a decrease in visual acuity of 5 points or
      more, increase of the central retinal thickness of 100 microm or more on OCT, or
      subjective deterioration with verifiable sub- or intraretinal fluid. RESULTS:
      During upload therapy an improvement in visual acuity of an average of +5.1
      letters (mean, n=82 eyes) was observed. During maintenance therapy it was
      initially possible to sustain this treatment effect. However, 5 months after
      loading therapy was concluded, a deterioration of -5.5 letters (mean, n=31) was
      evident in comparison with the end of loading therapy. During the further course
      deterioration continued (12-month follow-up: -8.6 letters, n=7). Recurrence
      occurred in 60% of the cases, on average 8 weeks after termination of loading
      therapy. During an observation period of 6 months (n=66) a total of 3.6
      injections were necessary. CONCLUSIONS: Therapy with intravitreal anti-VEGF
      medications represents a treatment option for RAP, but in the long term the
      disease continues to progress accompanied by functional deterioration. We thus
      recommend that patients with RAP be monitored at 4-week intervals to permit early
      treatment of recurrence.

PMID- 18607602
TI  - [Bioptics with multifocal lenses and Lasek].
AB  - PURPOSE: Good functional results with multifocal lenses need exact postoperative
      emmetropia. Therefore, it seems reasonable to perform additional refractive
      surgery to correct minimal spherical or cylindrical postoperative ametropia
      (bioptics). But concerns could arise about additional photoptic phenomena or loss
      of contrast. The literature contains only a few reports about bioptics after
      multifocal lens implantation. METHOD: In eight eyes of seven patients, laser
      subepithelial keratomileusis (Lasek) was done after multifocal lens implantation.
      Pre-Lasek and 6 months postoperatively, we performed the following examinations
      in addition to visual acuity: contrast sensitivity (Pelli-Robson charts), low
      contrast visual acuity (Humphrey AR 570), glare visual acuity (Humphrey AR 570),
      and night-driving ability (Mesoptometer II, Oculus). RESULTS: Preoperative
      contrast sensitivity was 1.2-1.65; postoperatively it was 1.35-1.65. Low-contrast
      visual acuity measured 50-70% preoperatively and 57-70% postoperatively. Glare
      visual acuity measured 12.5-50% preoperatively and 28.5-57% postoperatively.
      Mesoptometer measurements did not change after Lasek; they revealed night-driving
      ability under strict criteria for four patients. CONCLUSIONS: Bioptics as a
      combination of multifocal lens implantation and Lasek does not cause a functional
      decline in low-contrast or glare visual acuity, but it minimizes postoperative
      ametropia. It seems superior to exclusive multifocal lens implantation.

PMID- 18607603
TI  - [Solitary extramedullary plasmocytoma of the conjunctiva].
AB  - There is a wide variety of conjunctival tumors. A good diagnosis can be reached
      by discussing the case history with the patient in conjunction with a slit-lamp
      examination. Presented here is the case of a 39-year-old patient with a rapidly
      growing conjunctival tumor on his left eye. After tumor resection and
      histological analysis, a plasmacytoma was found. The completed hemato-oncological
      analysis gave no further suspicious pathological results, leading to the
      diagnosis of a solitary extramedullary plasmacytoma. Percutaneous radiotherapy
      was carried out.

PMID- 18607604
TI  - [Ocular neuromyotonia after radiation therapy].
AB  - Ocular neuromyotonia is a rare disease that is diagnosed mainly in patients
      treated with radiation. All such patients described in the literature presented
      with temporary diplopic images as a common symptom. In our case, the patient
      described an abducens paresis of the right eye combined with a sporadic exotropia
      half a year after radiation treatment of an epipharynx carcinoma. An adduction
      deficit on the right side could be triggered by holding the gaze to the right
      over a longer period of time, leading to exotropia in the primary position and
      gaze to the left. Symptoms were reduced with carbamazepine.

PMID- 18607605
TI  - [Computer-based graphic documentation of retinal findings].
AB  - AIM: To develop a software package that improves the standardized clinical
      documentation of retinal findings. In the clinical routine, retinal findings are
      usually documented with sketchy freehand drawings and supplementary handwritten
      remarks. Documentation features of common ophthalmologic software products
      include only simple sketching functions, which are limited to a change in
      location, size, or color of graphic primitives (e.g., ovals, rectangles, lines,
      textboxes). As a result, a feasible creation of standardized graphic
      documentation in retinal imaging is almost impossible. METHODS: We developed a
      Java-based software tool that features quick and intuitive generation of fundus
      schemes, which can be printed as a findings sheet or digitally archived.
      Particularly for clinical ophthalmologists, we created a set of standardized
      symbols that can be digitally rendered for graphic documentation. All symbols
      were integrated into a graphics library and separated in specific categories:
      preoperative, postoperative, angiomas and tumors, and retinopathy of prematurity.
      The user can simply choose the required symbol from the library and place it onto
      the retina scheme using drag-and-drop functionality. RESULTS: The practicability
      of existing features for graphic documentation of retinal findings is not
      sufficient because freehand drawings are too time-consuming and also share the
      risk of false interpretation due to individual handwriting. In contrast to
      freehand sketching, our software tool not only allows faster graphic creation but
      also improves medical documentation using a standardized symbol library, which is
      also specifically categorized. CONCLUSIONS: Graphic symbols for retinal
      documentation have found universal acceptance by ophthalmologists for a long
      time, but their practical use is still not efficient in clinical routine. This
      report shows how the appropriate use of software technology can contribute to
      documentation quality and clinical practice.

PMID- 18607606
TI  - [Autologous serum and alternative blood products for the treatment of ocular
      surface disorders].
AB  - Eye drops made from autologous serum have been increasingly used in the past
      decade to treat ocular surface disorders such as persistent epithelial defects
      and dry eye. Due to biologically active ingredients such as growth factors,
      vitamins, and nutrients, they can be used to lubricate the ocular surface and
      support epithelial wound healing. According to current legal requirements, they
      can be dispensed only for outpatient treatment if the producer has obtained a
      license from the appropriate local authorities. Therefore, the production and
      dispensing of autologous serum eye drops in Germany is currently limited to a
      very few institutions and their patients. We review the current evidence on the
      use of serum eye drops, recommend a standard protocol for their production, and
      describe a number of recently emerging alternative blood products for the
      treatment of ocular surface diseases along with their potential advantages and
      limitations.

PMID- 18607607
TI  - [Introduction to the topic: blood products for treatment of diseases of the
      ocular surface. Voodoo or standard therapy].

PMID- 18607608
TI  - Single port access laparoscopic right hemicolectomy.
AB  - BACKGROUND: Single port access (SPA) surgery is a rapidly evolving field as it
      combines some of the cosmetic advantage of the Natural Orifice Translumenal
      Endoscopic Surgery (NOTES) and allows performing surgical procedure with standard
      surgical instruments. We report in this paper a new technique of umbilical SPA
      right hemicolectomy with conventional surgical oncologic principle and technique
      of minimally invasive colectomy. METHODS: Preliminary experience with umbilical
      SPA right hemicolectomy in a patient with degenerated ascending colon polyp.
      RESULTS: Umbilical SPA right hemicolectomy was feasible with conventional
      laparoscopic instruments. Carcinologic surgical principle can be respected using
      this technique as pathological specimen had sufficient surgical margins (>10 cm)
      and lymph nodes (33). Operative time was 158 min. No peroperative or
      postoperative complications were recorded. CONCLUSION: SPA right hemicolectomy is
      feasible and safe when performed by experienced laparoscopic surgeons. SPA right
      hemicolectomy may have the advantage over NOTES approach to offer the safety of
      laparoscopic colectomy especially for haemostasis and anastomosis. It has to be
      determined whether or not this approach would offer benefit to patients, except
      in cosmesis, compared to standard laparoscopic right hemicolectomy.

PMID- 18607609
TI  - Ultrastructural localization of TDP-43 in filamentous neuronal inclusions in
      various neurodegenerative diseases.
AB  - Using post-embedding immunogold electron microscopy, TAR DNA-binding protein of
      43 kDa (TDP-43) was localized to neuronal cytoplasmic (NCI) and intranuclear
      (NII) inclusions, as well as unmyelinated neurites, in frontotemporal lobar
      degeneration with ubiquitinated inclusions (FTLD-U), amyotrophic lateral
      sclerosis (ALS), Alzheimer's (AD), Pick's disease (PiD) and Lewy body disease
      (LBD). The TDP-43 immunoreactive structures were morphologically heterogeneous.
      The most common was characterized by bundles of 10-20 nm diameter straight
      filaments with electron dense granular material within NCI, NII and neurites.
      This type of pathology was found in FTLD-U, ALS and some cases of AD. Less often,
      inclusions in neuritic processes of FTLD-U and some cases of AD contained 10-17
      nm diameter straight filaments without granular material. A final type of TDP-43
      immunoreactivity was labeling of filaments and granular material associated with
      tau filaments in neurofibrillary tangles of AD and Pick bodies of PiD or alpha
      synuclein filaments in Lewy bodies of LBD. The results suggest that TDP-43 is the
      primary component of the granulofilamentous inclusions in FTLD-U and ALS. Similar
      inclusions sometimes accompany filamentous aggregates composed of other abnormal
      proteins in AD, PiD and LBD.

PMID- 18607610
TI  - Suture anchor fixation strength in osteopenic versus non-osteopenic bone for
      rotator cuff repair.
AB  - INTRODUCTION: Rotator cuff tears are increasing with age. Does osteopenic bone
      have an influence on the pullout strength of suture anchors? MATERIALS AND
      METHODS: SPIRALOK 5.0 mm (DePuy Mitek), Super Revo 5 mm and UltraSorb (both
      ConMed Linvatec) suture anchors were tested in six osteopenic and six healthy
      human cadaveric humeri. Incremental cyclic loading was performed. The ultimate
      failure load, anchor displacement, and the mode of failure were recorded.
      RESULTS: In the non-osteopenic bone group, the absorbable SPIRALOK 5.0 mm
      achieved a significantly better pullout strength (274 N +/- 29 N, mean +/- SD)
      than the titanium anchor Super Revo 5 mm (188 N +/- 34 N, mean +/- SD), and the
      tilting anchor UltraSorb (192 N +/- 34 N, mean +/- SD). In the osteopenic bone
      group no significant difference in the pullout strength was found. The failure
      mechanisms, such as anchor pullout, rupture at eyelet, suture breakage and
      breakage of eyelet, varied between the anchors. CONCLUSION: The present study
      demonstrates that, in osteopenic bone, absorbable suture anchors do not have
      lower pullout strengths than metal anchors. In normal bone, the bioabsorbable
      anchor in this study even outperformed the non-absorbable anchor.

PMID- 18607611
TI  - Fresh stress fractures of lumbar pedicles in an adolescent male ballet dancer:
      case report and literature review.
AB  - Stress fracture in the pars interarticularis is a common cause of low back pain
      in young athletes. Pedicle stress fractures have also been reported in adolescent
      sport players, and most of them were associated with contralateral spondylolysis.
      Only a few cases with bilateral pedicle stress fractures have been reported. We
      report a 14-year-old ballet dancer with fresh bilateral pedicle fractures treated
      conservatively, together with a review of the literature.

PMID- 18607612
TI  - The risk of hepatotoxicity during long-term and low-dose flutamide treatment in
      hirsutism.
AB  - OBJECTIVE: Flutamide is an effective drug in treatment of hirsutism.
      Hepatotoxicity occasionally may occur with therapeutic doses (750-1500 mg/day), 3
      months after initiation of treatment. Monitoring of serum aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels is recommended
      to obviate serious hepatotoxicity. MATERIALS AND METHODS: Two hundred and
      fourteen patients with mean age of 20.9+/-2.34 years suffering from hirsutism
      were included in the study. Of these 214 women, 117 had diagnosis of polycystic
      ovarian syndrome (PCOS), and 97 had diagnosis of idiopathic hirsutism. Thirty age
      matched (mean age 20.3+/-2.0 years) normal women without signs of hirsutism and
      with normal menstrual cycle served as control group. Hirsutism was assessed using
      modified Ferriman-Gallwey method at the beginning and at the end of the
      treatment. Serum levels of luteinizing hormone (LH), follicle stimulant hormone
      (FSH), prolactin (PRL), estradiol (E2), androstenodion (A), testosterone (T),
      dehydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS),
      dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-P), sex hormone binding
      protein (SHBG), and ACTH were measured. Pelvic ultrasonography was performed for
      diagnosis of PCOS. Fifty-seven patients with PCOS (group 1) were given flutamide
      125 mg/day + oral contraceptive. Sixty patients with PCOS (group 2) were given
      flutamide 250 mg/day + oral contraceptive. Forty-seven patients with IH (group 3)
      were given flutamide 125 mg/day alone, and 50 patients with IH (group 4) were
      given flutamide 250 mg alone. Thirty women in control group (group 5) were given
      placebo only. ALT and AST levels were measured in the beginning of the treatment,
      and repeated after 3, 6, 9 and 12 months. RESULTS: No incidence of increase in
      AST or ALT levels (>or= 45 U/L) was observed in any of the groups. No evidence of
      hepatotoxicity in any of the 214 hyperandrogenic women was observed on low-dose
      flutamide for 1 year. CONCLUSION: We conclude that flutamide in a dosage of 125
      or 250 mg daily is a safe drug in the long-term treatment of hirsutism. The
      follow-up of patients receiving flutamide can be done by monitoring AST or ALT
      levels for hepatotoxicity.

PMID- 18607613
TI  - Psoas abscess in obstetrics.
AB  - Psoas abscess is rarely encountered in obstetric practice. This condition may be
      primary or secondary resulting from extension of an infectious process near the
      psoas muscle. We report a series of three patients with psoas abscess that were
      encountered in our obstetric practice. Two of these patients had a primary and
      one a secondary abscess. Two patients underwent laparotomy and drainage of
      abscess while one received medical treatment. All patients recovered
      uneventfully.

PMID- 18607614
TI  - Retention of intratumor injections of cisplatinum in murine tumors and the impact
      on laser thermal therapy for cancer treatment.
AB  - Recent studies using murine models of human squamous cell carcinoma (SCCA) have
      revealed a significant improvement in survival and cure rate of animals
      transplanted with human SCCA when treated with a combination of intratumor
      injections of chemotherapy and laser induced thermal therapy (LITT). These
      preliminary results suggest that this novel combination therapy may lead to
      improved clinical response compared to either treatment modality alone. Using a
      murine model of human SCCA we investigated two different modes of intratumor
      injection of cisplatin: a sustained-release cisplatin gel implant (CDDP/gel)
      versus cisplatin in solution (CDDP) at varying doses (range 1-3 mg/ml). In
      addition, we tested CDDP/gel combined with LITT. Results showed optimal drug
      concentration (30-300 nM) at tumor margins up to 4 h after injection of CDDP/gel
      implant compared to 3 nM at 5 min after injection with CDDP solution. Combined
      CDDP/gel and laser therapy significantly decreased tumor volume (P<0.05), with
      recurrence in only 25% of animals tested, compared to 78% tumor regrowth after
      LITT alone. These results suggest that laser chemotherapy may be an effective
      treatment for head and neck SCCA.

PMID- 18607615
TI  - Allele frequencies of 11 X-chromosomal loci in a population sample from Ghana.
AB  - Eleven X-chromosomal short tandem repeats (STRs) from two multiplex PCR
      approaches (DXS6807, DXS8378, DXS7132, DXS6800, DXS9898, DXS7424, DXS101,
      DXS7133, HPRTB, DXS8377, and DXS7423), located in four different X-chromosomal
      linkage groups, were typed in a population sample from Ghana, Africa. After
      genotyping unrelated men (129) and women (114) from the Ashanti population,
      forensic efficiency parameters such as polymorphism information content and mean
      exclusion chance were calculated. A deviation from the Hardy-Weinberg equilibrium
      could not be found. The investigation of 11 father-daughter and seven mother-son
      meioses revealed no mutations in any STR analyzed. Our data were compared with
      European, African-American, and Asian populations from the literature.

PMID- 18607616
TI  - The Microbial Rosetta Stone: a database system for tracking infectious
      microorganisms.
AB  - The Microbial Rosetta Stone (MRS) database system was developed to support the
      law enforcement community by providing a comprehensive and connected microbial
      pathogen data-information repository. To handle the myriad types of pathogen
      information required to support law enforcement and intelligence community
      investigations, a data model previously developed for medical and epidemiological
      information was enhanced. The data contained in MRS are a broad collection of
      expert-curated microbial pathogen information, but given the multitude of
      potential microbes and toxins that may be used in a biocrime or bioterrorism act
      continual information collection and updating are required. The MRS currently
      relates governmental community-specific pathogen priority lists, sequence
      metadata, taxonomic classifications, and diseases to strain collections, specific
      detection and treatment protocols, and experimental results for biothreat agents.
      The system contains software tools that help to load, curate, and connect the
      data. A shared MRS database can be populated in real time by multiple users in
      multiple locations. Querying tools also provide simple and powerful means to
      access the data in any part of the database.

PMID- 18607617
TI  - Prooxidant-antioxidant balance, peroxide and catalase activity in the aqueous
      humour and serum of patients with exfoliation syndrome or exfoliative glaucoma.
AB  - BACKGROUND: Oxidative stress plays an important role in the pathobiology of
      exfoliation syndrome (XFS) and exfoliative glaucoma (XFG). METHODS: We
      investigated the prooxidant-antioxidant balance (PAB) in aqueous humour and serum
      samples of 20 consecutive cases of XFS, 20 of XFG, and 20 age-matched controls,
      employing a recently described novel assay. The activity of catalase and the
      levels of (hydrogen) peroxide were also measured in these samples. RESULTS: There
      was no significant difference between the PAB in the aqueous humour of the XFS
      group (82.5 +/- 10 AU) and age-matched control patients (78.9 +/- 13.4 AU; p >
      0.05). A significant shift of the PAB balance in favour of oxidants was detected
      in the XFG group (90.2 +/- 7.6 AU) compared with controls (p < 0.001). In the
      serum of patients with XFS (138.8 +/- 13.2 AU) and XFG (124.08 +/- 13.50 AU), PAB
      was significantly altered in favour of oxidants as compared to age-matched
      controls (114.9 +/- 9.91 AU); p < 0.001). Catalase activity in the aqueous from
      XFS (10.1 +/- 4.5 U/ml) and XFG (12.2 +/- 6 U/ml) patients was significantly
      lower than that measured in the normal aqueous (14.6 +/- 1.9 U/ml). Similarly, a
      significantly lower catalase activity was found in XFS (103 +/- 21.4 U/ml) and
      XFG (116 +/- 38 U/ml) serum samples compared with controls (189.6 +/- 84.3 U/ml).
      Finally, (hydrogen) peroxide concentration in aqueous and serum samples from
      patients with XFS (aqueous: 26.9 +/- 6.6 microM; serum: 41 +/- 10 microM) and XFG
      (aqueous: 21.7 +/- 7 microM; serum: 32 +/- 4 microM) were significantly higher
      than that of the controls (aqueous: 9.6 +/- 5.8 microM; serum: 24 +/- 9 microM; p
      < 0.001). CONCLUSIONS: These findings suggest that in XFS oxidative stress is
      counterbalanced in the aqueous, whereas the development of XFG is accompanied by
      a disruption of this balance in favour of oxidants.

PMID- 18607618
TI  - Psychosocial working conditions and self-reported health in a representative
      sample of wage-earners: a test of the different hypotheses of the Demand-Control
      Support-Model.
AB  - PURPOSE: This paper presents an in-depth examination of the demand-control
      support-model (DCS-model). Each hypothesis of the DCS-model is tested: the main
      effects of job demands, job autonomy, task variation and social support; the
      additive effects of job strain, active learning and iso-strain; and the
      interactive buffer-effects of job autonomy, task variation and support on job
      demands. METHODS: Data from a representative cross-sectional sample of 11,099
      male and female wage-earners are investigated using log linear methods. The
      outcome measures are self-reported persistent fatigue, musculoskeletal complaints
      and emotional well-being. RESULTS: There is some support for each of the
      hypotheses. Quantitative job demands and superior support have the strongest
      effects. The job autonomy and buffer hypotheses are only partially supported.
      CONCLUSIONS: The strong effects of job demands, support, job strain and active
      learning are suggesting that a policy aimed at improving psychosocial working
      conditions should focus on a bearable level of job demands and the quality of
      social relationships at work.

PMID- 18607619
TI  - The contribution of upper limb and total body movement to adolescents' energy
      expenditure whilst playing Nintendo Wii.
AB  - Little research documents the contribution of upper limb and total body movement
      to energy expenditure (EE) during active video gaming. To address this, EE, heart
      rate (HR), and, upper limb and total body movement were assessed in 11- to 17
      year-old adolescents whilst playing three active (Nintendo Wii) and one sedentary
      (XBOX 360) video games. Non-dominant upper limb activity, EE and HR were
      significantly greater during Wii Sports boxing [mean 267.2 (SD 115.8) J kg(-1)
      min(-1); 136.7 (24.5) beats min(-1)] than tennis or bowling (P < or = 0.044). For
      all active games hip activity best predicted EE (R (2) > or = 0.53), with two
      measure models of HR and single-site activity data, and multi-site activity data,
      similarly explaining the variance in EE (R (2) > or = 0.64). The physiological
      cost of upper-body orientated active video games increased when movement of both
      upper limbs was encouraged. Improvements in EE explanatory power provide support
      for multi-site activity monitoring during unique, non-ambulatory activities.

PMID- 18607621
TI  - Cortical activity of skilled performance in a complex sports related motor task.
AB  - A skilled player in goal-directed sports performance has the ability to process
      internal and external information in an effective manner and decide which pieces
      of information are important and which are irrelevant. Focused attention and
      somatosensory information processing play a crucial role in this process.
      Electroencephalographic (EEG) recordings are able to demonstrate cortical changes
      in conjunction with this concept and were examined during a golf putting
      performance in an expert-novice paradigm. The success in putting (score) and
      performance-related cortical activity were recorded with an EEG during a 5 x 4
      min putting series. Subjects were asked to putt balls for four min at their own
      pace. The EEG data was divided into different frequencies: Theta (4.75-6.75 Hz),
      Alpha-1 (7-9.5 Hz), Alpha-2 (9.75-12.5 Hz) and Beta-1 (12.75-18.5 Hz) and
      performance related power values were calculated. Statistical analysis shows
      significant better performance in the expert golfers (P < 0.001). This was
      associated with higher fronto-midline Theta power (P < 0.05) and higher parietal
      Alpha-2 power values (P < 0.05) compared to the novices in golf putting. Frontal
      Theta and parietal Alpha-2 spectral power in the ongoing EEG demonstrate
      differences due to skill level. Furthermore the findings suggest that with
      increasing skill level, golfers have developed task solving strategies including
      focussed attention and an economy in parietal sensory information processing
      which lead to more successful performance. In a theoretical framework both
      cortical parameters may play a role in the concept of the working memory.

PMID- 18607622
TI  - Look before you leap: on the issue of muscle mass assessment by dual-energy X-ray
      absorptiometry (reply to Jordan Robert Moon comments).

PMID- 18607623
TI  - A model of associative learning in the mushroom body.
AB  - The mushroom body is a prominent invertebrate neuropil strongly associated with
      learning and memory. We built a high-level computational model of this structure
      using simplified but realistic models of neurons and synapses, and developed a
      learning rule based on activity dependent pre-synaptic facilitation. We show that
      our model, which is consistent with mushroom body Drosophila data and
      incorporates Aplysia learning, is able to both acquire and later recall CS-US
      associations. We demonstrate that a highly divergent input connectivity to the
      mushroom body and strong periodic inhibition both serve to improve overall
      learning performance. We also examine the problem of how synaptic conductance,
      driven by successive training events, obtains a value appropriate for the
      stimulus being learnt. We employ two feedback mechanisms: one stabilises strength
      at an initial level appropriate for an association; another prevents strength
      increase for established associations.

PMID- 18607624
TI  - Gastric remnant cancer: an old problem with novel concerns.
AB  - BACKGROUND AND AIMS: The patients with cancers in the remnant stomachs after
      previous partial resections for benign diseases constitute a peculiar subset of
      the patients with gastric cancer. They are generally at advanced stages on
      admissions due to disregarding the symptoms related to cancer. PATIENTS AND
      METHODS: Twenty six patients with cancer arising from the remnant stomach were
      analyzed. Clinicopathologic features such as age, gender, time interval between
      the initial operation and diagnosis of gastric remnant cancer, preoperative
      symptoms, surgical management, and tumor characteristics like size, location,
      histopathology, depth of invasion, lymph node involvement, presence of distant
      metastasis, and stages were documented. RESULTS: None of the cancers were
      diagnosed by routine surveillance and all the patients were symptomatic at the
      time of diagnosis. Twenty five patients were qualified for surgery. The
      resectability rate was 61% (n = 16). The ability to perform a curative resection
      and tumor location at the anastomotic site were determined as the factors
      significantly influencing survival (p < 0.05). CONCLUSION: Curative resection has
      to be the goal of surgical management in patients with gastric remnant cancer.
      Concerning clinician should be sceptical about a newly developing cancer in order
      to detect it in an early stage and enhance resectability.

PMID- 18607625
TI  - Long-term comorbidity of diabetes mellitus is a risk factor for perineal wound
      complications after an abdominoperineal resection.
AB  - BACKGROUND: This report is an attempt to clarify the effect of diabetes mellitus
      on perineal wound complications including infectious entities and delayed wound
      healing after abdominoperineal resection and also tried to show the risk factors
      for perineal wound complications. MATERIAL AND METHODS: The data of 80 patients
      who underwent an abdominoperineal resection were reviewed from April 1996 to
      March 2006. RESULTS: The rate of perineal wound complications is higher in
      diabetics (67%) than in nondiabetics (18%, p = 0.005). In a multivariate
      analysis, diabetes mellitus and operation time (> or =420 min) were the risk
      factors for perineal wound complications (p = 0.040, p = 0.027, respectively).
      Infectious perineal wound complication was associated with diabetes mellitus (p <
      0.001) but not with the operation time (p = 0.097). Furthermore, a longer
      comorbid duration of diabetes (> or =10 years) was a significant predictor for
      perineal wound complications (p = 0.008). CONCLUSION: This study demonstrated
      diabetes mellitus to be independently associated with perineal wound
      complications, and when the patients have diabetes mellitus, especially with a
      longer comorbid duration and longer operation time, the clinical path should be
      changed to reduce perineal wound complications.

PMID- 18607626
TI  - Allergen-induced airway hyperresponsiveness is absent in ecto-5'-nucleotidase
      (CD73)-deficient mice.
AB  - Adenosine is formed from extracellular purines by ecto-5'-nucleotidase (CD73) and
      is an essential player in allergic airway inflammation. The contribution of
      adenosine and other purines to electrolyte transport and mucociliary clearance
      was studied in airways of allergen challenged mice. No signs for allergen-induced
      inflammation were found in CD73-/- mice, and adenosine monophosphate (AMP) was
      unable to elicit airway Cl(-) secretion in these animals. Tracheas of ovalbumin
      (OVA)-treated BALB/c and CD73+/+ mice were hyperresponsive towards methacholine
      when assessed by Penh and direct optical measurement of contraction. In addition
      Cl(-) secretion activated by ATP and ADP was enhanced. These changes were not
      observed in CD73-/- mice. Expression of CFTR or CLCA was unchanged upon OVA
      treatment of CD73 mice, suggesting enhanced Cl(-) secretion due to upregulated
      purinergic pathways. Mucociliary clearance was determined by measuring particle
      transport in excised mouse tracheas and was strongly enhanced in OVA-challenged
      CD73+/+ mice, but remained unchanged in CD73-/- mice. While mucociliary clearance
      is activated by allergen exposure independent of functional ecto-5'-nucleotidase,
      airway inflammation is largely dependent on CD73. Thus, ecto-5'-nucleotidase may
      provide a novel target for therapeutic intervention, probably by local
      application of ecto-5'-nucleotidase inhibitors through inhalation.

PMID- 18607627
TI  - Effects of high temperature coupled with high light on the balance between
      photooxidation and photoprotection in the sun-exposed peel of apple.
AB  - The sun-exposed peel of 'Gala' apple with or without sunburn was compared in
      terms of photooxidation and photoprotection, and a controlled experiment was
      conducted to probe the initial responses of PSII to high light and high
      temperature. The content of carotenoids, lutein and xanthophylls on a chlorophyll
      basis was higher in the sunburned peel although they were lower expressed on a
      peel area basis. Significant loss of beta-carotene and neoxanthin was observed
      relative to chlorophylls in the sunburned peel. O(2) evolution rates and the
      activity of key enzymes in the Calvin cycle were lower in the sunburned peel, but
      the activity of these enzymes decreased to a lesser extent than the O(2)
      evolution rates. The activity of antioxidant enzymes in the ascorbate-glutathione
      cycle and the level of total ascorbate, total glutathione, and reduced
      glutathione were higher in the sunburned peel. However, the sunburned peel had
      higher H(2)O(2) and malondialdehyde contents. Fruit peels treated with high
      temperature (45 degrees C) alone showed a clear "K" step in their chlorophyll
      fluorescence transients whereas high temperature coupled with high light (1,600
      micromol m(-2) s(-1)) led to the disappearance of the "K" step and a further
      decrease in F (V)/F (M) (similar to what was observed in the sunburned peel). We
      conclude that high temperature coupled with high light damages the PSII complexes
      at both the donor and acceptor sides. Although both the xanthophyll cycle and the
      antioxidant system are up-regulated in response to the photooxidative stress,
      this up-regulation does not provide enough protection against the photooxidation.

PMID- 18607629
TI  - Clinicopathological features with outcomes of a series of conventional and
      proximal-type epithelioid sarcomas, diagnosed over a period of 10 years at a
      tertiary cancer hospital in India.
AB  - Epithelioid sarcoma (ES) is an uncommon sarcoma. Lately, its variants, including
      proximal-type ES, have been recognized. The present study highlights
      clinicopathological features of 26 (65%) conventional and 14 (35%) cases of
      proximal-type ES. Thirty-eight percent of cases were seen in 21-30-year age
      group, including 77.5% cases in men. Extremities were the commonest sites in both
      the subtypes. Histologically, conventional-type ES displayed nodular tumor
      aggregates with necrosis, while proximal-type showed solid arrangement of large,
      "rhabdoid-like" cells. More cases (64.2%) of the proximal type were of grade 3. A
      range of differential diagnoses was considered. Most important
      immunohistochemical markers were vimentin, epithelial membrane antigen,
      cytokeratin, CD34, and desmin. Maximum (72.5%) cases were treated surgically.
      Recurrences and metastasis were observed more in the proximal type. The 7-year
      disease-free survival was 19.4% in the conventional and nil in the proximal
      subtype (p = 0.06). The overall survival rate was also lower in the proximal
      (31.3%) than conventional type (90.2%; p < 0.001). Other unfavorable parameters
      were deeper location, larger size, and higher tumor stage. This unusual sarcoma,
      with characteristic growth patterns, merits a proper histological evaluation, as
      it has many mimics. Proximal-type ES is rather a morphological subtype,
      associated with an aggressive course.

PMID- 18607628
TI  - The involvement of calcium in the regulation of GPX1 expression.
AB  - Detrimental effects of salinity on plants are known to be partially alleviated by
      external Ca(2+). Previously we demonstrated that in citrus cells, phospholipid
      hydroperoxide glutathione peroxidase (GPX1) is induced by salt and its activation
      can be monitored by pGPX1::GUS fusion in transformed tobacco cells. In this paper
      we further characterized the induction of GPX1 by additional treatments, which
      are known to affect Ca(2+) transport. Omission of Ca(2+) changed the pattern of
      the transient salt-induced expression of GPX1 and chelation of Ca(2+) by EGTA, or
      treatment with caffeine, abolished the salt-induced GPX1 transcript. On the other
      hand, La(3+) was found to be as potent as NaCl in inducing GPX1 transcription and
      the combined effect of La(3+) and NaCl seemed to be additive. Pharmacological
      perturbation of either external or internal Ca(2+) pools by La(3+), EGTA,
      caffeine, Ca(2+) channel blockers, or a Ca(2+)-ATPase inhibitor rendered the
      imposed salt stress more severe. Except for La(3+), all these Ca(2+) effectors
      had no effect on their own. In addition, the fluidizer benzyl alcohol
      dramatically increased the NaCl-induced GPX1 transcription. Taken together, our
      results show that: 1) the mode of action of La(3+) on GPX1 expression differs
      from its established role as a Ca(2+) channel blocker, 2) membrane integrity has
      an important role in the perception of salt stress, and 3) internal stores of
      Ca(2+) are involved in activating GPX1 expression in response to salt stress. We
      propose that the common basis for these effects lies in the membrane bound
      Ca(2+).

PMID- 18607630
TI  - Late-onset adrenal hypoplasia congenita caused by a novel mutation of the DAX-1
      gene.
AB  - Mutation in the orphan nuclear receptor DAX-1 gene causes X-linked adrenal
      hypoplasia congenita (AHC). Affected male children classically suffer a salt
      losing crisis and adrenal insufficiency in their early infancy or, in some rare
      exceptions, with late-onset subtype. We report here a patient manifesting late
      onset adrenal hypoplasia congenita caused by the premature truncation of the C
      terminus of the DAX-1 molecule, which is essential for its function as a
      transcriptional repressor. A 12-year-old boy was referred to us after being
      afflicted with generalized skin pigmentation for about 3 years, fatigue and
      headache. Primary adrenal insufficiency was determined on the basis of a low
      plasma cortisol level (3.9 microg/dl) despite an extremely high ACTH level (1200
      pg/ml). Replacement therapy with hydrocortisone and fludorocortisone acetate was
      initiated soon thereafter. Hypogonadotropic hypogonadism was confirmed at the age
      of 18 years, at which time sexual infantilism had become apparent. Direct
      sequencing of the peripheral lymphocyte-derived DNA revealed a novel 1033del13
      mutation on the ligand-binding domain of the NR0B1 (DAX-1) gene, which generated
      a premature stop codon truncating the C-terminus. This mutation was considered de
      novo since we could not find it in his mother. This case demonstrates that even a
      truncated protein lacking the major functional domain of DAX-1 can present late
      onset and latent adrenal failure.

PMID- 18607632
TI  - Effects of transforming growth factor-beta 1 and ascorbic acid on differentiation
      of human bone-marrow-derived mesenchymal stem cells into smooth muscle cell
      lineage.
AB  - Bone-marrow-derived mesenchymal stem cells (MSCs) can differentiate into a
      variety of cell types including smooth muscle cells (SMCs). We have attempted to
      demonstrate that, following treatment with transforming growth factor-beta 1 (TGF
      beta1) and ascorbic acid (AA), human bone-marrow-derived MSCs differentiate into
      the SMC lineage for use in tissue engineering. Quantitative polymerase chain
      reaction for SMC-specific gene (alpha smooth muscle actin, h1-calponin, and
      SM22alpha) expression was performed on MSCs, which were cultured with various
      concentrations of TGF-beta1 or AA. TGF-beta1 had a tendency to up-regulate the
      expression of SMC-specific genes in a dose-dependent manner. The expression of
      SM22alpha was significantly up-regulated by 30 microM AA. We also investigated
      the additive effect of TGF-beta1 and AA for differentiation into SMCs and
      compared this effect with that of other factors including platelet-derived growth
      factor BB (PDGF-BB). In addition to SMC-specific gene expression, SMC-specific
      proteins increased by two to four times when TGF-beta1 and AA were used together
      compared with their administration alone. PDGF did not increase the expression of
      SMC-specific markers. MSCs cultured with TGF-beta1 and AA did not differentiate
      into osteoblasts and adipocytes. These results suggest that a combination of TGF
      beta1 and AA is useful for the differentiation of MSCs into SMCs for use in
      tissue engineering.

PMID- 18607631
TI  - Impact of transcriptional, ABA-dependent, and ABA-independent pathways on
      wounding regulation of RNS1 expression.
AB  - Injured plants induce a wide range of genes whose products are thought to help to
      repair the plant or to defend against opportunistic pathogens that might infect
      the wounded plant. In Arabidopsis thaliana L., oligogalacturonides (OGAs) and
      jasmonic acid (JA) are the main regulators of the signaling pathways that control
      the local and systemic wound response, respectively. RNS1, a secreted
      ribonuclease, is induced by wounding in Arabidopsis independent of these two
      signals, thus indicating that another wound-response signal exists. Here we show
      that abscisic acid (ABA), which induces wound-responsive genes in other systems,
      also induces RNS1. In the absence of ABA signaling, wounding induces only
      approximately 45% of the endogenous levels of RNS1 mRNA. However, significant
      levels of RNS1 still accumulate in the absence of ABA signaling. Our results
      suggest that wound-responsive increases in ABA production may amplify induction
      of RNS1 by a novel ABA-independent pathway. To elucidate this novel pathway, we
      show here that the wound induction of RNS1 is due in part to transcriptional
      regulation by wounding and ABA. We also show evidence of post-transcriptional
      regulation which may contribute to the high levels of RNS1 transcript
      accumulation in response to wounding.

PMID- 18607633
TI  - Characteristics of retinal stem cells from rat optic cup at embryonic day 12.5
      (tailbud stage).
AB  - Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair
      of such damage by cell transplantation is one of the most feasible types of
      central nervous system treatment. Retinal stem cells (RSC) are a substrate for
      cell-replacement therapy, and previous studies have shown that RSCs from
      different developmental stages have distinct properties in proliferative capacity
      and differentiation potential. The tailbud stage is of special interest in
      retinogenesis, because RSCs commence differentiation after this period. However,
      no information about the characteristics of RSCs from the tailbud stage is
      available. In this study, the characteristics of cell cultures from the rat optic
      cup (referred to as optic-cup-derived RSCs; OC-RSCs) at embryonic day 12.5
      (tailbud stage) were analyzed. OC-RSCs grew either as monolayers or as
      neurospheres in the presence of basic fibroblast growth factor and could be
      dissociated into a single cell suspension. Using the MTT assay, immunochemistry,
      cytogenetic analysis, and flow cytometry, we found that OC-RSCs were easily
      enriched to 92% by three passages, had a normal diploid karyotype, and exhibited
      no obvious differences in proliferative rate during eight passages (doubling
      time: 36 h). OC-RSCs produced retinal specific cells after the addition of serum
      to the medium, but the differentiation potential was affected by serum
      concentration. Preliminary results showed that transplanted OC-RSCs were
      incorporated into the degenerated retina of RCS rats and differentiated into
      rhodopsin-positive cells. Thus, OC-RSCs, after suitable enrichment, provide a
      population of stem cells with distinct growth and differentiation properties that
      make them suitable for research into RSC differentiation and transplantation.

PMID- 18607634
TI  - Ecological gradient of sexual selection: elevation and song elaboration in
      finches.
AB  - Ecological gradients in natural and sexual selection often result in evolutionary
      diversification of morphological, life history, and behavioral traits. In
      particular, elevational changes in habitat structure and climate not only covary
      with intensity of sexual selection in many taxa, but may also influence evolution
      of mating signals. Here we examined variation in courtship song in relation to
      elevation of breeding across cardueline finches-a subfamily of birds that
      occupies the widest elevational range of extant birds and shows extensive
      variation in life histories and sexual selection along this range. We predicted
      that decrease in sexual selection intensity with elevation of breeding documented
      in this clade would result in a corresponding evolutionary reduction in
      elaboration of courtship songs. We controlled for the effects of phylogeny,
      morphology, and habitat structure to uncover a predicted elevational decline in
      courtship song elaboration; species breeding at lower elevations sang more
      elaborated and louder songs compared to their sister species breeding at higher
      elevations. In addition, lower elevation species had longer songs with more
      notes, whereas frequency components of song did not vary with elevation. We
      suggest that changes in sexual selection account for the observed patterns of
      song variation and discuss how elevational gradient in sexual selection may
      facilitate divergence in mating signals potentially reinforcing or promoting
      speciation.

PMID- 18607635
TI  - Voles on small islands: effects of food limitation and alien predation.
AB  - Ecosystems of three trophic levels may be bottom-up (by food-plant availability)
      and/or top-down (by predators) limited. Top-down control might be of greater
      consequence when the predation impact comes from an alien predator. We conducted
      a replicated two-factor experiment with field voles (Microtus agrestis) during
      2004-2005 on small islands of the outer archipelago of the Baltic Sea, south-west
      Finland, manipulating both predation impact by introduced American mink (Mustela
      vison) and winter food supply. In autumn 2004, we live-trapped voles on five
      islands from which mink had been consistently removed, and on four islands where
      mink were present, and provided half of these islands with 1.8 kg oats per vole.
      Body mass of female voles increased as a response to supplementary food, whereas
      both food supplementation and mink removal increased the body mass of male voles
      in subsequent spring. During winter, there was a positive effect of supplementary
      food, but in the subsequent summer, possible positive long-term impacts of food
      supplementation on field voles were not detected. Mink removal appeared not to
      affect density estimates of field voles during the winter and summer immediately
      after food addition. Trapping data from 2004 to 2005 and 2007 suggested, however,
      that in two out of three summers densities of voles were significantly higher in
      the absence than in the presence of mink. We conclude that vole populations on
      small islands in the archipelago of the Baltic Sea are mainly bottom-up limited
      during winter (outside the growing season of food plants), when food availability
      is low, and limited by mink predation during summer which slows population growth
      during the reproductive season of voles.

PMID- 18607636
TI  - Enemy-free space and habitat-specific host specialization in a butterfly.
AB  - The majority of herbivorous insects have relatively specialized food habits. This
      suggests that specialization has some advantage(s) over generalization.
      Traditionally, feeding specialization has been thought to be linked to digestive
      or other food-related physiological advantages, but recent theory suggests that
      generalist natural enemies of herbivorous insects can also provide a major
      selective pressure for restricted host plant range. The European swallowtail
      butterfly Papilio machaon utilizes various plants in the Apiaceae family as
      hosts, but is an ecological specialist being monophagous on Angelica archangelica
      in southern Sweden. This perennial monocarp grows in three seaside habitat types:
      (1) on the barren rocky shore in the absence of any surrounding vegetation, (2)
      on the rocky shore with some surrounding vegetation, and (3) on species-rich
      meadows. The rocky shore habitat harbors few invertebrate generalist predators,
      whereas a number of invertebrate predators abound in the meadowland habitat.
      Here, we test the importance of enemy-free space for feeding specialization in
      Papilio machaon by assessing survival of larvae placed by hand on A. archangelica
      in each of the three habitat types, and by assessing the habitat-specificity of
      adult female egg-laying behavior by recording the distribution of eggs laid by
      free-flying adult females among the three habitat types. Larval survival was
      substantially higher in the rocky shore habitat than in the meadowland and
      significantly higher on host plants without surrounding vegetation on the rocky
      shore. Eggs laid by free-flying females were found in all three habitat types,
      but were significantly more frequent in the rocky shore habitat, suggesting that
      females prefer to lay eggs in the habitat type where offspring survival is
      highest. These results show that larval survivorship on the same host plant
      species can be strongly habitat-specific, and suggest that enemy-free space is an
      underlying factor that drives feeding specialization in Papilio machaon.

PMID- 18607637
TI  - Anti-GBM antibodies co-exist with MPO-ANCA in a 4-year-old girl with acute renal
      failure.

PMID- 18607638
TI  - Factors associated with acute renal failure in children with rhabdomyolysis.
AB  - Pigment nephropathy accounts for approximately 3% of all cases of acute renal
      failure (ARF) in children. Studies of risk factors associated with ARF and the
      need for renal replacement therapy (RRT) in children with rhabdomyolysis
      associated pigment nephropathy consist of retrospective case series with variable
      inclusion criteria. Our objective was to evaluate clinical and laboratory
      characteristics, etiology, initial fluid therapy, prevalence of ARF and the
      requirement for RRT in pediatric patients with acute rhabdomyolysis. Twenty-eight
      patients (19 male) with a mean age of 11.1 +/- 5.6 years were studied. Acute
      renal failure occurred in 11 patients (39%), seven of whom (64%) required RRT.
      Features associated with the need for RRT included history of fever, persistent
      oliguria, admission blood urea nitrogen level, creatinine, Ca(2+), K(+),
      bicarbonate and aspartate aminotransferase. Most of these factors are related to
      the level of renal insufficiency and degree of muscle injury. There was no
      difference in admission and peak creatine kinase (CK) levels between those who
      did or did not require RRT. However, all who required RRT had a peak CK level >
      5000 U/L.

PMID- 18607639
TI  - Birth weight [corrected] and elevated albumin to creatinine ratio in youth with
      diabetes: the SEARCH for Diabetes in Youth study.
AB  - Low birth weight (BWT) may contribute to kidney disease and could explain some of
      the variance in the development of early diabetic kidney disease. This hypothesis
      was tested in the multicenter SEARCH study (3,714 youth with diabetes <20 years
      of age). A morning spot urine sample, laboratory and anthropometric data, and a
      medical history were obtained. Elevated albumin to creatinine ratio (ACR) was
      defined as > or =30 mcg albumin/mg creatinine, and BWT was categorized as low
      (<2,500 g), reference (2,500-4,000 g), or high (>4,000 g). The relationship of
      BWT to elevated ACR was analyzed using multiple logistic regression. In youth
      with diabetes, the prevalence of elevated ACR was 12.6% in those with low BWT,
      9.7% in those with reference BWT, and 8.9% in those with high BWT. BWT category
      was not significantly associated with elevated ACR (p = 0.23). Those with
      diabetes duration >18 months (2,032) had the following association of BWT
      category with elevated ACR [odds ratio (OR) = 1.64, 95% confidence interval (CI)
      1.00-2.69, p = 0.0503] for low BWT compared with reference BWT. Whereas low BWT
      may be a factor in kidney disease, little evidence was found of a relationship
      between low BWT and elevated ACR in this study population of youth with diabetes.

PMID- 18607640
TI  - Hyponatremia in pediatric community-acquired pneumonia.
AB  - Studies focusing on serum sodium disorders in children with community-acquired
      pneumonia (CAP) are nearly entirely lacking, though clinical experience suggests
      that at least hyponatremia (HN) might be rather common. We evaluated the
      incidence of hypo- and hypernatremia, in relation to other clinical, laboratory
      and etiological findings, in pediatric CAP. Serum sodium concentration was
      measured in 108 ambulatory and hospitalized children with radiologically
      confirmed CAP of variable severity. The etiology of CAP was revealed by serology
      in 97 patients. HN (serum sodium < 135 mmol/l) was present in 49 (45.4%)
      children, and it was mild (> 130 mmol/l) in 92% of the cases. On admission,
      hyponatremic patients had higher body temperature (38.96 degrees C vs 38.45
      degrees C, P = 0.008), white blood cell count (21,074/microl vs 16,592/microl, P
      = 0.008), neutrophil percentage (78.93% vs 69.33%, P = 0.0001), serum C-reactive
      protein (168.27 mg/l vs 104.75 mg/l, P = 0.014), and serum procalcitonin (22.35
      ng/ml vs 6.87 ng/ml, P = 0.0001), and lower calculated osmolality (263.39
      mosmol/l vs 272.84 mosmol/l, P = 0.0001) than normonatremic ones. No association
      was found with plasma glucose, type of radiological consolidation or etiology of
      CAP. HN is common but usually mild in children with CAP. HN seems to be
      associated with the severity of CAP, assessed by fever, need of hospitalization
      and serum non-specific inflammatory markers.

PMID- 18607641
TI  - Left renal vein entrapment: a frequent feature in children with postural
      proteinuria.
AB  - In most Asian subjects with postural proteinuria, ultrasonic imaging and Doppler
      flow scanning disclose entrapment of the left renal vein in the fork between the
      aorta and the superior mesenteric artery. Little information is available on the
      possible occurrence of left venal rein entrapment in European subjects with
      postural proteinuria. Renal ultrasound with Doppler flow imaging was therefore
      performed on 24 Italian or Swiss patients with postural proteinuria (14 girls and
      ten boys, aged between 5.2 years and 16 years). Signs of aorto-mesenteric left
      renal vein entrapment were noted in 18 of the 24 subjects. In conclusion, aorto
      mesenteric left renal vein entrapment is common also among European subjects with
      postural proteinuria.

PMID- 18607642
TI  - Ambulatory blood pressure in children with diabetes 1.

PMID- 18607643
TI  - Inhibition of water absorption in human proximal tubular epithelial cells in
      response to Shiga toxin-2.
AB  - Postdiarrhea hemolytic uremic syndrome (HUS) is the most common cause of acute
      renal failure in children in Argentina. It is well established that Shiga toxin
      type 2 (Stx2) causes direct damage to glomerular endothelial cells and tubular
      epithelial cells, leading to a reduction in the water handling capacity of the
      kidney. In this study, we demonstrate that Stx2 and its B subunit (Stx2B) were
      able to inhibit water absorption across human renal tubular epithelial cell
      (HRTEC) monolayers without altering the short circuit current and the (3)H
      mannitol permeability. Quantitative evaluation of (14)C-inulin transport across
      HRTEC monolayers showed a similar transport rate both before and after HRTEC
      treatment with Stx2 that confirmed the integrity of the paracellular pathway.
      Furthermore, Stx2 produced significant protein synthesis inhibition of HRTEC at
      concentrations as low as 0.001 ng/ml and 1 h of incubation, whereas Stx2B did not
      modify it at concentrations as high as 10,000 ng/ml and 6 h of incubation. Our
      findings suggest that whereas the action of Stx2 appears to be caused mainly by
      the inhibition of protein synthesis mediated by the A subunit, the binding of
      Stx2B subunit to the Gb3 receptor may affect the membrane mechanisms related to
      water absorption. We speculate that inhibition of water absorption may occur in
      proximal tubular cells in vivo in response to Stx2 and may contribute to the
      early event of HUS pathogenesis.

PMID- 18607644
TI  - Deficiency of intrarenal angiotensin II type 2 receptor impairs paired homeo box
      2 and N-myc expression during nephrogenesis.
AB  - We previously demonstrated that angiotensin II (Ang II) stimulates paired homeo
      box-2 (Pax-2) via the Ang II type 2 receptor (AT(2)R). The Pax-2 gene and N-myc
      play pivotal roles in renal morphogenesis via their effects on cell proliferation
      and differentiation in embryonic mesenchymal cells and embryonic mouse kidneys.
      Since AT(2)R knock-out (KO) mice have a phenotype that is similar to that of
      humans with congenital renal and urinary tract anomalies (CAKUT) and develop
      hypertension in adulthood, these mice and wild-type controls were used for this
      study. Embryonic kidneys isolated from E12 to term gestation were cultured in
      Dulbecco's modified Eagle's medium (DMEM) with or without Ang II (10(-6) M) for
      24 h ex vivo. Renal morphogenesis was histologically assessed. Mean glomerular
      tuft volume was determined by the method of Weibel and Gomez with the aid of
      image analysis software. Pax-2 and N-myc gene expression were determined by
      immunostaining as well as by Western blotting and real-time-quantitative
      polymerase chain reaction (RT-qPCR). Glomerular size was significantly smaller,
      and Pax-2 and N-myc expression down-regulated, in kidneys of AT(2)R KO mice
      compared with those of wild-type mice. In ex vivo studies, Ang II stimulated Pax
      2 and N-myc mRNA expression in embryonic kidneys of wild-type mice, but this
      stimulatory effect was absent in embryonic kidneys of AT(2)R KO mice. Taken
      together, these data indicate that intrarenal AT(2)R plays an important role in
      nephrogenesis. Deficiency of AT(2)R may impair both Pax-2 and N-myc expression,
      eventually resulting in glomerular hyperfiltration that may, ultimately, lead to
      later development of hypertension.

PMID- 18607645
TI  - Nephronophthisis.
AB  - Nephronophthisis (NPH) is an autosomal recessive disease characterized by a
      chronic tubulointerstitial nephritis that progress to terminal renal failure
      during the second decade (juvenile form) or before the age of 5 years (infantile
      form). In the juvenile form, a urine concentration defect starts during the first
      decade, and a progressive deterioration of renal function is observed in the
      following years. Kidney size may be normal, but loss of corticomedullary
      differentiation is often observed, and cysts occur usually after patients have
      progressed to end-stage renal failure. Histologic lesions are characterized by
      tubular basement membrane anomalies, tubular atrophy, and interstitial fibrosis.
      The infantile form is characterized by cortical microcysts and progression to end
      stage renal failure before 5 years of age. Some children present with extrarenal
      symptoms: retinitis pigmentosa (Senior-Loken syndrome), mental retardation,
      cerebellar ataxia, bone anomalies, or liver fibrosis. Positional cloning and
      candidate gene approaches led to the identification of eight causative genes
      (NPHP1, 3, 4, 5, 6, 7, 8, and 9) responsible for the juvenile NPH and one gene
      NPHP2 for the infantile form. NPH and associated disorders are considered as
      ciliopathies, as all NPHP gene products are expressed in the primary cilia,
      similarly to the polycystic kidney disease (PKD) proteins.

PMID- 18607646
TI  - The impact of excess heat events in Maricopa County, Arizona: 2000--2005.
AB  - Exposure to excess heat is preventable yet it is the primary weather-related
      cause of mortality in the United States. In the Southwest United States, high
      temperatures are common and indoor environments often have cooling devices. In
      summer 2005, Maricopa County, Arizona experienced a 182% increase in reported
      heat-related deaths in comparison to 2000--2004. We examined at-risk populations
      and excess mortality. We characterized heat-related deaths using descriptive and
      multivariate time-series analyses of county vital record data from June-September
      2000--2005. Dose-response relationships for heat-related mortality and heat index
      were evaluated using linear and quadratic splines. From June-September, 2000-
      2005, 136 heat-related deaths (0.68 per 100,000) were reported; 49 (36%) occurred
      in 2005. In July 2005, a 14-day heat wave resulted in 28 (57%) reported deaths--a
      102% increase in comparison to the same time period in 2000--2004. Decedent
      demographics in 2005 did not differ from previous years. The mean age of all 136
      deaths was 56 years (range: 7-92 years). Of those with discernable reported
      injury locations, 62 (66%) were identified outdoors. Forty-eight (77%) decedents
      identified outdoors were < 5 years; conversely, 26 (82%) decedents who were found
      indoors were > or = 65 years. A 6% (95% CI: 1.00-1.13) increase in mortality risk
      was observed for each degree (F) increase in heat index. Excess heat impacted a
      younger population in Maricopa County and many deaths occurred outdoors.
      Consecutive days of heat exposure--even among a heat-acclimated population--can
      increase mortality risk. Public health response activities guided by locally
      obtained data will better target those at risk.

PMID- 18607647
TI  - Management in non-traumatic arm, neck and shoulder complaints: differences
      between diagnostic groups.
AB  - Arm, neck and/or shoulder complaints are common in western societies. In the
      Netherlands, general practice guidelines are issued on shoulder pain and
      epicondylitis only. Little is known about actual management of the total range of
      diagnoses. The objectives of the study are: to determine management in patients
      consulting the GP with a new episode of non-traumatic arm neck and shoulder
      complaints up to 6 months after the first consultation. To evaluate differences
      in management between patients with specific diagnoses versus non-specific
      diagnoses and between specific diagnostic groups. In a prospective cohort study
      in general practice. We recruited 682 eligible patients. Data on diagnosis,
      management, patient- and complaint-characteristics were collected. Co-occurrence
      of treatment options was presented in scaled rectangles. After 6 months,
      additional diagnostic tests had been performed in 18% of the patients, mainly
      radiographic examination (14%). Further, 49% had been referred for physiotherapy
      and 12% to the medical specialist. Patients with specific diagnoses were more
      frequently referred for specialist treatment, and patients with non-specific
      diagnoses for physiotherapy. Corticosteroid injections (17%) were mainly applied
      specific diagnoses (e.g. impingement syndrome, frozen shoulder, carpal tunnel and
      M. Quervain). Frequencies of prescribed medication (51%) did not differ between
      specific and non-specific diagnoses. In 19% of the patients no referral,
      prescribed analgesics or injection was applied. Braces (4%) were mainly
      prescribed in epicondylitis. Overall, management most frequently consisted of
      prescribed analgesics and referral for physiotherapy. Specific and non-specific
      diagnostic subgroups differed in the frequency corticosteroid injections were
      applied, and referrals to physiotherapy and to a medical specialist.

PMID- 18607648
TI  - A mechanistic and electrochemical study of the interaction between dimethyl
      sulfide dehydrogenase and its electron transfer partner cytochrome c2.
AB  - Dimethyl sulfide dehydrogenase isolated from the photosynthetic bacterium
      Rhodovulum sulfidophilum is a heterotrimeric enzyme containing a molybdenum
      cofactor at its catalytic site, as well as five iron-sulfur clusters and a heme b
      cofactor. It oxidizes dimethyl sulfide (DMS) to dimethyl sulfoxide in its native
      role and transfers electrons to the photochemical reaction center. There is
      genetic evidence that cytochrome c2 mediates this process, and the steady state
      kinetics experiments reported here demonstrated that cytochrome c2 accepts
      electrons from DMS dehydrogenase. At saturating concentrations of both substrate
      (DMS) and cosubstrate (cytochrome c2), Michaelis constants, KM,DMS and KM,cyt of
      53 and 21 microM, respectively, were determined at pH 8. Further kinetic analysis
      revealed a "ping-pong" enzyme reaction mechanism for DMS dehydrogenase with its
      two reactants. Direct cyclic voltammetry of cytochrome c2 immobilized within a
      polymer film cast on a glassy carbon electrode revealed a reversible FeIII/II
      couple at +328 mV versus the normal hydrogen electrode at pH 8. The FeIII/II
      redox potential exhibited only minor pH dependence. In the presence of DMS
      dehydrogenase and DMS, the peak-shaped voltammogram of cytochrome c2 is
      transformed into a sigmoidal curve consistent with a steady-state (catalytic)
      reaction. The cytochrome c2 effectively mediates electron transfer between the
      electrode and DMS dehydrogenase during turnover and a significantly lower
      apparent electrochemical Michaelis constant K'M,DMS of 13(+/-1) microM was
      obtained. The pH optimum for catalytic DMS oxidation by DMS dehydrogenase with
      cytochrome c2 as the electron acceptor was found to be approximately 8.3.

PMID- 18607649
TI  - Computational study of the binding of CuII to Alzheimer's amyloid-beta peptide:
      do Abeta42 and Abeta40 bind copper in identical fashion?
AB  - One of the many hypotheses on the pathogenesis of Alzheimer's disease is that the
      amyloid-beta peptide (Abeta) binds CuII and can catalytically generate H2O2,
      leading to oxidative damage in brain tissues. For a molecular level understanding
      of such catalysis it is critical to know the structure of the Abeta-CuII complex
      precisely. Unfortunately, no high-resolution structure is available to date and
      there is considerable debate over the copper coordination environment with no
      clear consensus on which residues are directly bound to CuII. Considering all
      plausible isomers of the copper-bound Abeta42 and Abeta40 using a combination of
      density functional theory and classical molecular dynamics methods, we report an
      atomic resolution structure for each possible complex. We evaluated the relative
      energies of these isomeric structures and surprisingly found that Abeta42 and
      Abeta40 display very different binding modes, suggesting that shorter peptides
      that are truncated at the C-terminus may not be realistic models for
      understanding the chemistry of the most neurotoxic peptide, Abeta42.

PMID- 18607650
TI  - Homology modeling and dynamics of the extracellular domain of rat and human
      neuronal nicotinic acetylcholine receptor subtypes alpha4beta2 and alpha7.
AB  - In recent years, it has become clear that the neuronal nicotinic acetylcholine
      receptor (nAChR) is a valid target in the treatment of a variety of diseases,
      including Alzheimer's disease, anxiety, and nicotine addiction. As with most
      membrane proteins, information on the three-dimensional (3D) structure of nAChR
      is limited to data from electron microscopy, at a resolution that makes the
      application of structure-based design approaches to develop specific ligands
      difficult. Based on a high-resolution crystal structure of AChBP, homology models
      of the extracellular domain of the neuronal rat and human nAChR subtypes
      alpha4beta2 and alpha7 (the subtypes most abundant in brain) were built, and
      their stability assessed with molecular dynamics (MD). All models built showed
      conformational stability over time, confirming the quality of the starting 3D
      model. Lipophilicity and electrostatic potential studies performed on the rat and
      human alpha4beta2 and alpha7 nicotinic models were compared to AChBP, revealing
      the importance of the hydrophobic aromatic pocket and the critical role of the
      alpha-subunit Trp-the homolog of AChBP-Trp 143-for ligand binding. The models
      presented provide a valuable framework for the structure-based design of specific
      alpha4beta2 nAChR subtype ligands aimed at improving therapeutic and diagnostic
      applications.

PMID- 18607651
TI  - Calcific discitis in children: vertebral body involvement (possible insight into
      etiology).
AB  - The aim of the study was to present our cases of calcific discitis, analyze the
      imaging findings, and review the literature in an attempt to formulate a possible
      etiology. We reviewed the imaging and clinical findings in nine patients with
      calcific discitis and accomplished a literature review of the condition. There
      were nine patients, five males and four females. Age range was 5-13 years with a
      mean of 9.7 years. Twenty-three discs were involved, nine cervical and fourteen
      thoracic. Four cervical discs were not calcified but merely swollen. One patient
      presented with abnormal magnetic resonance (MR) signal changes within a vertebral
      body. Our literature search revealed another such patient and brought up the
      possibility that the insult to the disc might be secondary to vertebral body
      involvement and disruption of the tenuous vascular/nutritional support of the
      intervertebral disc from the adjacent vertebral body. In the early stages of
      calcific discitis, only swelling and expansion of the disc are seen. More
      recently, with MR imaging, vertebral body involvement has been demonstrated to
      also occur. As a result, it may be that the initial insult (vascular compromise)
      is to the vertebral body (nutritional support for the disc) rather than to the
      disc.

PMID- 18607652
TI  - Automatic quantity processing in 5-year olds and adults.
AB  - In this study adults performed numerical and physical size judgments on a
      symbolic (Arabic numerals) and non-symbolic (groups of dots) size congruity task.
      The outcomes would reveal whether a size congruity effect (SCE) can be obtained
      irrespective of notation. Subsequently, 5-year-old children performed a physical
      size judgment on both tasks. The outcomes will give a better insight in the
      ability of 5-year-olds to automatically process symbolic and non-symbolic
      numerosities. Adult performance on the symbolic and non-symbolic size congruity
      tasks revealed a SCE for numerical and physical size judgments, indicating that
      the non-symbolic size congruity task is a valid indicator for automatic
      processing of non-symbolic numerosities. Physical size judgments on both tasks by
      children revealed a SCE only for non-symbolic notation, indicating that the lack
      of a symbolic SCE is not related to the mathematical or cognitive abilities
      required for the task but instead to an immature association between the number
      symbol and its meaning.

PMID- 18607657
TI  - Genetic relatedness among tdh+ and trh+ Vibrio parahaemolyticus cultured from
      Gulf of Mexico oysters (Crassostrea virginica) and surrounding water and
      sediment.
AB  - Pathogenic Vibrio parahaemolyticus (Vp) (tdh(+)/trh(+)) represent a small
      percentage of environmental Vp populations, and very little is known about this
      subpopulation. Repetitive extragenic palindromic PCR and multilocus sequence
      analysis revealed heterogeneity among 41 Vp containing thermostable direct
      hemolysin (tdh) and tdh-related hemolysin (trh) that were isolated from
      Mississippi coastal environments from October 2006 to April 2007. There was no
      source-specific sequestering in oysters, water, or sediment.

PMID- 18607659
TI  - Repair of UVB-damaged skin by the antioxidant sulphated flavone glycoside
      thalassiolin B isolated from the marine plant Thalassia testudinum Banks ex
      Konig.
AB  - Daily topical application of the aqueous ethanolic extract of the marine sea
      grass, Thalassia testudinum, on mice skin exposed to UVB radiation resulted in a
      dose-dependent recovery of the skin macroscopic alterations over a 6-day period.
      Maximal effect (90%) occurred at a dose of 240 microg/cm(2), with no additional
      effects at higher doses. Bioassay-guided fractionation of the plant extract
      resulted in the isolation of thalassiolin B (1). Topical application of 1 (240
      microg/cm(2)) markedly reduces skin UVB-induced damage. In addition, thalassiolin
      B scavenged 2,2-diphenyl-2-picrylhydrazyl radical with an EC(50) = 100 microg/ml.
      These results suggest that thalassiolin B is responsible for the skin
      regenerating effects of the crude extract of T. testudinum.

PMID- 18607662
TI  - Excision of painful bipartite patella: good long-term outcome in young adults.
AB  - Excision of the accessory bipartite fragment is widely used, but its long-term
      outcome is not known. We evaluated the outcome after surgical excision of a
      symptomatic accessory bipartite or multipartite patella fragment in young adult
      men performing their compulsory military service and determined the incidence of
      painful bipartite patellae in this group of skeletally mature adults. We followed
      25 of 32 patients for a minimum of 10 years (mean, 15 years; range, 10-22 years).
      The incidence of painful, surgically treated bipartite patella was 9.2 per
      100,000 recruits. Patients' median age at surgery was 20 years. There were 19
      superolateral and six lateral bipartite fragments. Other radiographic findings
      were rare. At followup, the Kujala score mean was 95 points (range, 75-100
      points), and osteoarthrotic changes (Kellgren-Lawrence Grade 1) were seen in two
      knees. No reoperations related to bipartite patella occurred during the followup.
      Symptomatic bipartite patella is rare and does not seem primarily associated with
      anatomic deviations, but when incapacitating pain persists despite nonoperative
      treatment, surgical excision seems to yield reasonable functional outcome and
      quick recovery with no apparent adverse sequelae. Our data suggest there is no
      reason to avoid this technically undemanding procedure for treating persistent
      symptoms of bipartite patella in young adults. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18607663
TI  - Thigh pain in a 53-year-old woman.

PMID- 18607664
TI  - Case report: two-step malignant transformation of a liposclerosing myxofibrous
      tumor of bone.
AB  - We present the case of a patient with malignant transformation of a
      liposclerosing myxofibrous tumor. The patient had a histologically confirmed
      liposclerosing myxofibrous tumor that, during a course of 22 months,
      spontaneously transformed into a lesion appearing like a benign giant cell
      reactive lesion and subsequently into a high-grade bone sarcoma. Few such cases
      of spontaneous malignant transformation of liposclerosing myxofibrous tumor have
      been reported. We report what we believe to be the first case documenting
      spontaneous transformation of a liposclerosing myxofibrous tumor into an
      intermediate lesion with benign-appearing histologic features and then into a
      high-grade malignant tumor.

PMID- 18607666
TI  - Determining the impact of Walk Kansas: applying a team-building approach to
      community physical activity promotion.
AB  - BACKGROUND: Research and practice partnerships have the potential to enhance the
      translation of research findings into practice. PURPOSE: This paper describes
      such a partnership in the development of Walk Kansas (WK) and highlights
      individual and organizational level outcomes. METHOD: Phase 1 examined: (a) the
      reach of WK, (b) physical activity changes, and (c) maintenance of physical
      activity changes 6 months after the program was completed. Phase 2 explored WK
      adoption and sustainability over 5 years. RESULTS: WK attracted a large number of
      participants who were more likely to be female, more active, and older than the
      adult population within the counties where they resided. Inactive or
      insufficiently active participants at baseline experienced significant increases
      in both moderate (p < 0.001) and vigorous (p < 0.001) physical activity. A random
      selection of participants who were assessed 6 months post-program did not
      demonstrate a significant decrease in moderate or vigorous activity between
      program completion and 6-month follow-up. The number of counties adopting the
      program increased across years, peaking at 97 in 2006 and demonstrated the
      sustainability of the WK over 5 years. CONCLUSIONS: WK is effective, has a broad
      reach, and enables participants to maintain increased activity. It also shows
      promise for broad adoption and sustainability.

PMID- 18607665
TI  - Specific tyrosine kinase inhibitors regulate human osteosarcoma cells in vitro.
AB  - Inhibitors of specific tyrosine kinases are attractive lead compounds for
      development of targeted chemotherapies for many tumors, including osteosarcoma.
      We asked whether inhibition of specific tyrosine kinases would decrease the
      motility, colony formation, and/or invasiveness by human osteosarcoma cell lines
      (TE85, MNNG, 143B, SAOS-2, LM-7). An EGF-R inhibitor reduced motility of all five
      cell lines by 50% to 80%. In contrast, an IGF-1R inhibitor preferentially reduced
      motility by 42% in LM-7 cells and a met inhibitor preferentially reduced motility
      by 80% in MNNG cells. The inhibitors of EGF-R, IGF-1R, and met reduced colony
      formation by more than 80% in all tested cell lines (TE85, MNNG, 143B). The EGF-R
      inhibitor reduced invasiveness by 62% in 143B cells. The JAK inhibitor increased
      motility of SAOS-2 and LM7 cells without affecting colony formation or
      invasiveness. Inhibitors of HER-2, NGF-R, and PDGF-Rs did not affect motility,
      invasiveness, or colony formation. These results support the hypothesis that
      specific tyrosine kinases regulate tumorigenesis and/or metastasis in
      osteosarcoma.

PMID- 18607667
TI  - Are constructs of the transtheoretical model for physical activity measured
      equivalently between sexes, age groups, and ethnicities?
AB  - BACKGROUND/PURPOSE: Identifying mediators of physical activity change requires
      measurement instruments that are reliable, valid, and generalizable to multiple
      populations. Despite continued application of the transtheoretical model (TTM) to
      the study of physical activity, the structural components of the TTM measurement
      instruments have been understudied in diverse populations. METHODS: A multiethnic
      sample (N = 700, M (age) = 47, 63% women, 38% Caucasian) of participants living
      in Hawaii completed TTM measures. The factor validity and measurement
      equivalence/invariance (ME/I) of decisional balance, barrier self-efficacy,
      temptations, and processes of change instruments were explored between men,
      women, age groups, and ethnicities. RESULTS/CONCLUSIONS: Measurement models of
      barrier self-efficacy and revised models of temptations and processes of change
      demonstrated sufficient evidence for ME/I among all subgroups. A revised model of
      decisional balance demonstrated sufficient evidence for ME/I between genders and
      among ethnicities, but not among age groups. Future research should examine the
      stability of these constructs across time.

PMID- 18607668
TI  - Functional crosstalk between cell-surface and intracellular channels mediated by
      junctophilins essential for neuronal functions.
AB  - Junctophilins (JPs) contribute to the formation of junctional membrane complexes
      between the plasma membrane and the endoplasmic/sarcoplasmic reticulum, and
      provide a structural platform for channel communication during excitation
      contraction coupling in muscle cells. In the brain, two neuronal JP subtypes are
      widely expressed in neurons. Recent studies have defined the essential role of
      neural JPs in the communication between cell-surface and intracellular channels,
      which modulates the excitability and synaptic plasticity of neurons in the
      cerebellum and hippocampus.

PMID- 18607669
TI  - Design of the POSSIBLE UStrade mark Study: postmenopausal women's compliance and
      persistence with osteoporosis medications.
AB  - Failure to take prescribed medication is common. The POSSIBLE US study is
      evaluating the impact of physician and patient characteristics on patient
      reported compliance and persistence with osteoporosis medications. We report our
      study design and the baseline characteristics of 4,994 postmenopausal women
      recruited from primary care physician offices in 33 states. INTRODUCTION: The
      Prospective Observational Scientific Study Investigating Bone Loss Experience
      (POSSIBLE US) is a longitudinal cohort study of osteoporosis therapy in primary
      care. METHODS: Between 2004 and 2007, 134 physicians (in 33 states) enrolled
      postmenopausal women initiating, changing, or continuing osteoporosis
      medications. After completing a baseline questionnaire, participants will provide
      data semi-annually for up to 3 years through 2008. Physicians provide patient
      data at baseline and routine follow-up visits. Participants from 23 sites also
      signed a release regarding administrative claims data for economic analyses and
      validation of self-reported data. BASELINE RESULTS: Four thousand nine hundred
      and ninety-four evaluable women were recruited from internal medicine (n =
      1,784), family practice (n = 1,556), obstetrics/gynecology (n = 1,556), and from
      one rheumatology practice (n = 98). Mean participant age was 64.3 years (SD =
      9.97); 89% were Caucasian; 59% had some college education. Sixty-three percent
      used a single osteoporosis agent, usually a bisphosphonate. For monotherapy
      patients, concordance between clinic- and patient-reported medication use was
      lowest for patients prescribed estrogen therapy (70%) or calcium/vitamin D (72%).
      Obstetrician/gynecologists enrolled younger women, who were more likely to use
      estrogen therapy than patients enrolled by other physicians. The 934 women (19%)
      prescribed only calcium/vitamin D were younger than women prescribed
      pharmacologic therapy. CONCLUSIONS: POSSIBLE US provides a unique foundation for
      evaluating longitudinal use of osteoporosis medications and related outcomes.

PMID- 18607670
TI  - Changes in soft tissue composition are the primary predictors of 4-year bone
      mineral density changes in postmenopausal women.
AB  - Changes in body weight influence bone mineral density, but the role of body
      composition is not clear in postmenopausal women. Body weight and soft tissue
      composition predicted bone changes independent of calcium supplementation and
      exercise frequency, indicating that soft tissue composition should be measured in
      clinical trials. INTRODUCTION: The purpose of this study was to examine the
      relationship between changes in body weight and composition and changes in 4-year
      bone mineral density (BMD) after accounting for age, 4-year exercise frequency
      (EX), and 4-year calcium supplement intake (CA) in postmenopausal women with and
      without hormone therapy (HT). METHODS: Postmenopausal women (aged 40-65 years)
      either using HT (for 1-3.9 years) or not using HT (for > or =1 year) were
      recruited to the study. EX and CA was monitored throughout the study and 167
      women completed 4 years. BMD and soft tissue composition measurements were made
      using dual-energy X-ray absorptiometry. Regression was used to predict 4-year BMD
      changes from EX, CA, age, baseline and 4-year changes in body weight and
      composition. HT users (n = 115, 55.3 +/- 4.3 years) and non-users (n = 52, 57.5
      +/- 4.7 years) were analyzed separately. RESULTS: The models predicting regional
      BMD changes that included soft tissue composition changes explained the most
      variation compared with those with body weight or EX and CA alone. Larger amounts
      of variation in BMD changes were explained in the no HT group. CONCLUSION: Body
      composition changes are important positive predictors of BMD changes independent
      of EX and CA supplementation, but their contribution varies according to bone
      site and with HT use.

PMID- 18607671
TI  - Utility of published guidelines on the use of nonsteroidal anti-inflammatory
      drugs in the elderly.
AB  - Canadian Consensus guidelines regarding appropriate use of nonsteroidal anti
      inflammatory drugs (NSAID) were recently published. This study was done to
      evaluate the application of these guidelines on NSAID practice patterns in frail
      elderly patients referred to a specialist Geriatric Assessment Clinic. A
      retrospective chart review was undertaken of referrals who were currently
      prescribed NSAIDs. Data were captured on age, sex, weight, diagnoses, medications
      and dosages, indication for NSAID treatment, lying BP (as assessed in the clinic)
      and recent serum creatinine result. Creatinine clearance was subsequently
      calculated use the Cockcroft-Gault equation. Complete data were available on 107
      patients (68% women, average age 80.6 years). Thirty percent were on a
      traditional NSAID, the remainder were on a Coxib. Concomitant aspirin was
      prescribed in 37%. Cytoprotection was being used in 38% and did not increase
      appreciably in patients with additional risk factors for GI toxicity, i.e.,
      concomitant aspirin usage (35%), and history of GI toxicity (48%). Sixty-seven
      were taking anti-hypertensive medications, although more than two thirds of these
      patients were uncontrolled. Newly diagnosed hypertension was present in 19.6%.
      Calculated creatinine clearance revealed moderate to severe renal impairment in
      79% of subjects, although serum creatinine was only elevated in 18%. In total,
      70% of subjects were found to have relative or absolute risk factors for NSAID
      therapy. Given the high prevalence of potential contraindications to anti
      inflammatory drug usage in this study, we advocate the dissemination and
      application of these guidelines in geriatric patients in an attempt to reduce
      potential morbidity and mortality.

PMID- 18607672
TI  - Identification of viral and non-viral reverse transcribing elements in pineapple
      (Ananas comosus), including members of two new badnavirus species.
AB  - A previously published partial sequence of pineapple bacilliform virus was shown
      to be from a retrotransposon (family Metaviridae) and not from a badnavirus as
      previously thought. Two newly discovered sequence groups isolated from pineapple
      were associated with bacilliform virions and were transmitted by mealybugs.
      Phylogenetic analyses indicated that they were members of new badnavirus species.
      A third caulimovirid sequence was also amplified from pineapple, but available
      evidence suggests that this DNA is not encapsidated, but more likely derived from
      an endogenous virus.

PMID- 18607673
TI  - Hop mosaic virus: complete nucleotide sequence and relationship to other
      carlaviruses.

PMID- 18607674
TI  - Characterization of antibody responses against a neutralizing epitope on the
      glycoprotein E2 of classical swine fever virus.
AB  - The sequence TAVSPTTLR is a conserved and linear neutralizing epitope on the
      glycoprotein E2 of classical swine fever virus. In this study, TAVSPTTLR-directed
      antibodies, induced either by virions or by an epitope-focused immunogen, were
      characterized. The results revealed that despite the same epitope specificity,
      the antibodies induced by different immunogens varied significantly both in the
      neutralizing test and in binding inhibition assays. This suggests that the
      protective immunity induced by this epitope is due to more than simply the
      epitope specificity and that this epitope might need essential contributions from
      its flanking context to induce functional epitope-specific antibodies.

PMID- 18607675
TI  - Lytic induction of Kaposi's sarcoma-associated herpesvirus in primary effusion
      lymphoma cells with natural products identified by a cell-based fluorescence
      moderate-throughput screening.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi's
      sarcoma primary effusion lymphoma (PEL), and multicentric Castleman's disease.
      Intentional lytic induction of gammaherpesviruses in the presence of antiviral
      drugs is thought to be an effective treatment option for gammaherpesvirus-related
      tumors. In this study, we used a cell-based fluorescence bioassay system in which
      a KSHV-infected PEL cell line was stably transfected with a potent viral-promoter
      driven reporter gene to identify effective non-toxic reagents capable of inducing
      latent KSHV. Among 400 plant extracts screened, three extracts increased reporter
      gene expression in a dose-dependent manner. Furthermore, the three extracts
      activated the RTA promoter and induced expression of lytic genes in the
      endogenous viral genomes of KSHV-infected tumor cells. Together, our results
      demonstrate the effectiveness of a moderate-throughput screening system to
      identify natural products capable of inducing KSHV reactivation, thereby
      facilitating the development of novel therapeutic agents for KSHV-associated
      malignancies.

PMID- 18607676
TI  - Novel interactions of TG2 with heparan sulfate proteoglycans: reflection on
      physiological implications.
AB  - This mini-review brings together information from publications and recent
      conference proceedings that have shed light on the biological interaction between
      transglutaminase-2 and heparan sulphate proteoglycans. We subsequently draw
      hypotheses of possible implications in the wound healing process. There is a
      substantial overlap in the action of transglutaminase-2 and the heparan sulphate
      proteoglycan syndecan-4 in normal and abnormal wound repair. Our latest findings
      have identified syndecan-4 as a possible binding and signalling partner of
      fibronectin-bound TG2 and support the idea that transglutaminase-2 and syndecan-4
      act in synergy.

PMID- 18607677
TI  - Malignant mesothelioma: current status and perspective in Japan and the world.
AB  - Malignant pleural mesothelioma (MPM) is associated with a poor prognosis; and to
      make things worse, its incidence is increasing throughout the world. Surgical
      management of MPM is comprised of two aspects: diagnosis and resection. Surgical
      biopsy with thoracoscopy provides a higher yield but a higher rate of tumor cell
      seeding than blind biopsy. In some surgical cases, extended surgical staging with
      mediastinoscopy, laparoscopy, and contralateral thoracoscopy is required for the
      preoperative evaluation for resectablity. There are two types of surgical
      resection for MPM. Pleurectomy/decortication (P/D) involves removal of as much of
      the visceral, parietal, and pericardial pleura and the tumor as possible without
      removing the underlying lung. Because P/D is less radical but less invasive
      compared to extrapleural pneumonectomy (EPP), it can be tolerated by poor-risk
      patients. EPP comprises en bloc resection of visceral, parietal, and pericardial
      pleura and adjacent components such as ipsilateral lung, pericardium, and
      diaphragm, without opening the pleural cavity. EPP was considered a highly
      dangerous procedure with a surgical mortality of more than 30% decades ago, but
      its current operative mortality/morbidity rates are 4%-9% and 60%, respectively.
      As macroscopic complete resection is the primary goal of surgery for MPM because
      of its diffuse intrapleural growth, surgical resection alone is associated with
      poor survival. In this context, combination therapy with surgery plus
      chemotherapy and/or radiotherapy is currently considered the standard treatment
      for patients with respectable MPM. A national survey of EPP was conducted
      recently in Japan, and a few multicenter clinical trials will start soon.

PMID- 18607678
TI  - Early and midterm outcome after off-pump coronary artery bypass grafting in
      patients with poor left ventricular function compared with patients with normal
      function.
AB  - OBJECTIVE: As there are few reports on the clinical results of off-pump coronary
      artery bypass (OPCAB) in patients with poor left ventricular (LV) function, the
      safety and efficacy of OPCAB surgery in such patients remains unclear. METHODS:
      From January 2002 to May 2007, a total of 519 consecutive patients underwent
      isolated myocardial revascularization via OPCAB. We compared the early and
      midterm results of 79 patients with poor LV function [ejection fraction (EF) <
      40%] with those of 319 patients with normal LV function (EF >or= 50%). Follow-up
      was completed in 96.2% of the patients. RESULTS: There were no significant
      intergroup differences in the number of grafts per patient or the rate of
      achievement of complete revascularization. No patient in either group was
      converted from off-pump to on-pump. The overall 30-day mortality was 1.0%. The
      mean follow-up was 3.0 +/- 1.3 years. Five-year freedom from death from all
      causes was 57.7% in the low-EF group and 83.6% in the normal-EF group. The rates
      of freedom from cardiac death were 73.2% and 93.7%, respectively; and the rates
      of freedom from the combined endpoint of cardiac death, myocardial infarction,
      repeat coronary intervention, and heart failure requiring treatment were 65.7%
      and 77.3%, respectively. CONCLUSION: OPCAB surgery in patients with poor LV
      function can be performed safely with the same quality in terms of the number of
      grafts and rate of complete revascularization as in patients with normal LV
      function. There are higher mortality and cardiac event rates in patients with
      poor LV function than those with normal LV function at the midterm evaluation
      after OPCAB.

PMID- 18607679
TI  - Patient-prosthesis mismatch after aortic valve replacement in the elderly.
AB  - PURPOSE: The aim of this study was to analyze the effect of patient-prosthesis
      mismatch (PPM) on survival and left ventricular mass regression in elderly
      patients after aortic valve replacement (AVR). MATERIALS AND METHODS: Data on
      patients >65 years old who underwent isolated AVR from 1990 and 2007 were
      analyzed retrospectively. A bioprosthesis was used in 42 cases and a mechanical
      valve in 59. The mean follow-up period was 3.1 years (0.1-14.2 years). The
      indexed effective orifice area (i-EOA) was determined from echocardiographic data
      in clinical reports in the literature and indexed to body surface area (cm2/m2).
      Mild PPM was defined as an i-EOA between 0.65 and 0.85. We also evaluated the New
      York Heart Association (NYHA) classification and the left ventricular mass (LVM)
      index. RESULTS: A total of 34 patients (33.6%) had PPM. No patient had an i-EOA
      <0.65. Freedom from valve-related death was 86.3% +/- 6.7% in the PPM-negative
      group and 85.7% +/- 7.9% in the PPM-positive group at 5 years after AVR. The mean
      LVM index (g/m2) decreased significantly (P < 0.01), from 239.2 to 167.4 in the
      PPM-negative group and from 229.1 to 154.4 in the PPM-positive group,
      respectively. NYHA functional status was excellent at late follow-up in both
      groups. CONCLUSION: Mild PPM occurred in a large proportion of elderly patients
      undergoing AVR but did not affect midterm survival or LV mass regression.

PMID- 18607680
TI  - Thymic carcinoma with dissemination: a retrospective analysis of ten patients.
AB  - OBJECTIVE: Thymic carcinoma is a rare mediastinal neoplasm with frequent pleural
      or pericardial dissemination. We retrospectively studied ten such cases and
      analyzed factors that influenced the survival of the patients. METHODS: Ten
      thymic carcinoma patients with dissemination have been treated since 1987. The
      clinical and pathological data were retrospectively reviewed. RESULTS:
      Pretreatment tumor biopsy was performed and demonstrated squamous cell carcinomas
      in nine and small cell carcinoma in one. In six of ten patients pleural or
      pericardial dissemination was clinically evident (cT4). These patients were
      basically regarded as inoperable and treated with chemotherapy and/or
      radiotherapy. Four other patients were diagnosed as cT3 preoperatively but were
      found to have dissemination at the time of thoracotomy. They underwent total
      resection of the thymic tumor and all visible pleural dissemination but without
      pericardial dissemination. Radiotherapy was performed pre-or postoperatively with
      or without chemotherapy. The 5-year survival rate in all patients was 42.0%. The
      patients with Masaoka stage IVa showed significantly better prognosis than the
      patients with stage IVb (MST, 69.7 months vs. 14.5 months; 5-year survival rate,
      64.3% vs. 0%) (P = 0.03). The patients with cT3 disease showed significantly
      better prognosis (P = 0.016) than the patients with cT4 disease (MST, 69.7 months
      vs. 14.5 months; 5-year survival rate, 100% vs. 16.7%). CONCLUSIONS: Among thymic
      carcinoma patients with pleural or pericardial dissemination, there seem to be
      some patients who show good prognosis. These candidates are patients who
      underwent subtotal resection with disseminations that were identified only at the
      operation and without hematogenous or lymphogenous metastasis.

PMID- 18607681
TI  - Surgical treatment for isolated coarctation of the aorta in an adult patient.
AB  - A 51-year-old woman developed heart failure due to severe hypertension of the
      upper half of the body caused by coarctation of the aorta. From the available
      surgical options for this condition, we selected bypass grafting from the left
      subclavian artery to the descending aorta for this patient.

PMID- 18607682
TI  - Poststernotomy pseudoaneurysm of the internal mammary artery.
AB  - We present a case of a 79-year-old man who underwent mitral valve and aortic
      valve replacement. The patient's postoperative period was almost uneventful. At
      his cardiac preoperative examination, a malignant tumor of the urinary tract had
      been suspected, so computed tomography (CT) was performed after discharge, on the
      48th postoperative day. The CT scan demonstrated a pseudoaneurysm of the internal
      mammary artery (IMA). Angiography demonstrated that it was a pseudoaneurysm of
      the left internal manmary artery. The lesion was embolized using coils, which
      successfully occluded the lesion.

PMID- 18607683
TI  - Acute nonbacterial pleuritis caused by spontaneous rupture of metastatic
      pulmonary adenocarcinoma.
AB  - Nonbacterial pleuritis caused by rupture of a metastatic adenocarcinoma is
      extremely rare and has not yet been reported. A 59-year-old man with a history of
      rectal cancer surgery 6 years earlier presented with a solitary lung mass in the
      periphery of the right lower lobe on computed tomography. Transbronchial biopsy
      disclosed a suspected metastatic adenocarcinoma, and he was admitted for
      pulmonary metastasectomy. He had been asymptomatic, but 4 weeks after the
      diagnostic bronchoscopy, the patient suddenly complained of a right back pain and
      dyspnea at rest; shortly after that, he developed a fever of 39 degrees C. A
      chest X-ray showed right pleural effusion, collapse of the right lower lobe, and
      elevation of the right diaphragmatic dome, but without pneumothorax. Emergent
      video-assisted thoracoscopy revealed a perforated tumor in the collapsed lower
      lobe, and a right lower lobectomy was carried out. The postoperative course was
      uneventful, and he was well without recurrent disease 2 years after pulmonary
      resection.

PMID- 18607684
TI  - Right ventricular myxoma obstructing the pulmonary artery during early childhood.
AB  - Primary cardiac tumors are uncommon during infancy and childhood. Myxomas
      originating in the right ventricle are even less common in pediatric patients. A
      2-year-old girl was referred to our hospital under a diagnosis of right
      ventricular tumor. The aim of the operation was extirpation of the tumor.
      Perioperative cardiac arrest occurred when the tumor obstructed the pulmonary
      artery. After promptly establishing cardiopulmonary bypass, the tumor was removed
      from the right ventricular outflow tract. The patient was discharged on the 13th
      postoperative day without complications.

PMID- 18607685
TI  - Successful management of postoperative acute respiratory distress syndrome in a
      patient with lung cancer.
AB  - Acute respiratory distress syndrome after pulmonary resection for lung cancer
      frequently has a lethal outcome. Treatment with a combination therapy of
      neutrophil elastase inhibitor and steroid administration was used to achieve good
      control, without impairing lung function, in a patient with postoperative acute
      respiratory distress syndrome. A 74-year-old man was diagnosed with lung cancer
      and referred to the outpatient department of Chiba University Hospital with
      double primary lung cancers located in the right upper lobe that were staged at
      T2N0M0 (stage IB). He underwent right upper lobectomy with hilar and mediastinal
      lymph node dissection. After 10 postoperative days, he had acute respiratory
      distress syndrome. He was given a corticosteroid and a neutrophil elastase
      inhibitor, which resulted in rapid improvement without lung dysfunction.

PMID- 18607686
TI  - Bridge to transplantation with a Toyobo-NCVC left ventricular assist device in a
      3-year-old girl.
AB  - In Japan, no pulsatile ventricular assist devices are available specifically for
      use in children. Pumps designed for adults are thus often used in children. We
      report herein a case of end-stage heart failure in a 3-year old girl (height
      100.4 cm; body weight 16.2 kg; body surface area 0.66 m2) who underwent
      implantation with an adult-sized Toyobo-NCVC left ventricular assist device
      (Toyobo-National Cardiovascular Center, Osaka, Japan) in our unit. We started
      with the driving mode to "full-fill, full-empty" mode. The problem was difficult
      to-treat hypertension due to excessive stroke volume induced by the left
      ventricular assist device. Aggressive administration of antihypertensive therapy
      was needed. Successful heart transplantation was performed in Germany 5 months
      after beginning support with the Toyobo-NCVC left ventricular assist device.

PMID- 18607687
TI  - Thymic carcinoma with combined resection of the hemisternum.
AB  - We report a case of partial resection of the hemisternum of a thymic carcinoma
      invading the right anterior chest wall. A computed tomographic scan of the chest
      and positron emission tomography showed a mass invading the right anterior chest
      wall in the anterior mediastinum with high 18F-fluorodeoxyglucose accumulation.
      An operation was performed to obtain a definitive diagnosis and achieve complete
      resection. First, we assessed the boundaries of gross disease using left-sided
      video-assisted thoracoscopy. After delineating the margins of the lesion invading
      the anterior chest wall, a median sternotomy was added and the tumor was resected
      with the right half of the sternum, parts of the right third and fourth costal
      cartilages, part of the right upper lung lobe, and pericardium. Histopathological
      evaluation revealed a squamous cell carcinoma of the thymus with direct invasion
      to the right lung, pericardium, and the right third costal cartilages.

PMID- 18607688
TI  - Thoracic and cardiovascular surgery in Japan during 2006: annual report by the
      Japanese Association for Thoracic Surgery.

PMID- 18607689
TI  - Lack of early augmentation of platelet reactivity after coronary intervention in
      patients treated with bivalirudin.
AB  - To determine whether a regimen of aspirin pretreatment, bivalirudin during the
      procedure and clopidogrel (600 mg) immediately after percutaneous coronary
      intervention (PCI) was associated with platelet activation during and shortly
      after (1 and 2 h) PCI, we characterized platelet function in 10 patients with the
      use of flow cytometry in the absence of agonist and in response to thrombin (10
      nM), ADP (1 microM), the collagen-mimetic convulxin (5 ng/ml), and platelet
      activating factor (10 nM). Activation of platelets in peripheral blood was rare
      (<0.5% of platelets) before, during and after PCI. Platelet reactivity in
      response to each of the agonists was lower after the PCI compared with that in
      blood taken before the PCI. Accordingly, platelet activation and platelet
      reactivity were not increased after elective PCI when patients were treated
      during the procedure with aspirin and bivalirudin and immediately after the
      procedure with a 600 mg loading dose of clopidogrel.

PMID- 18607690
TI  - Effects of estrogen on age-related changes in muscarinic responsiveness of the
      urinary bladder and lumbosacral dorsal root ganglion cells in female rats.
AB  - The aim of this study was to investigate estrogen's effect on age-related changes
      in bladder function. Female Wistar rats were divided into three groups that
      included young rats (3-month-old) (YR), old rats (13-month-old) (OR), and old
      rats given subcutaneous treatments of estradiol for 6 weeks (OR + E). The groups
      were evaluated for (i) micturition behavior, (ii) changes of detrusor
      contractility and frequency of detrusor contraction in response to muscarinic
      stimulation in cystometrograms, (iii) messenger RNA (mRNA) expression of the
      muscarinic receptor subtype in the detrusor muscle, as measured by real-time
      polymerase chain reaction, and (iv) the immunoreactivity of P2X(3), CGRP, and
      substance P in the lumbosacral dorsal root ganglia. There were no significant
      changes for the average micturition volumes or micturition frequencies seen among
      the three groups. Moreover, there were no significant differences in the
      proportion of the immunoreactivities of P2X(3), CGRP, and substance P in afferent
      neurons among these three groups. However, an intravenous administration of
      muscarine significantly increased the frequency during continuous cystometrograms
      in the OR and OR + E groups. In these groups, there was a significant increase in
      the expression of the M(2) receptor mRNAs as compared to YR. It appears that the
      up-regulation of the M(2) receptor may lead to a decreased intercontraction
      interval by muscarinic stimuli. OR + E rats showed a significant increase in
      bladder weight as compared to the OR group. The muscarine-stimulated
      contractility of the detrusor in the cystometrogram also exhibited a significant
      increase in the OR + E group as compared to the OR group, which resulted from
      estrogen-induced functional hypertrophy of the detrusor muscle. These findings
      suggest that as little as 6 weeks of estrogen treatment is capable of improving
      the detrusor contractility, although the treatment contributes little to the
      storage phase of the micturition cycle.

PMID- 18607691
TI  - Proteomic analysis of cardiac metabolic enzymes in asphyxiated newborn piglets.
AB  - Hypoxia/reoxygenation (H/R) creates an energetic deficiency in the heart, which
      may contribute to myocardial dysfunction. We hypothesized that H/R-induced
      impairment of cardioenergetic enzymes occurs in asphyxiated newborn animals.
      After hypoxia for 2 h (10-15% oxygen), newborn piglets were resuscitated with
      100% oxygen for 1 h, followed by 21% oxygen for 3 h. Sham-operated control
      piglets had no H/R. Hemodynamic parameters in the piglets were continuously
      measured. At the end of experiment, hearts were isolated for proteomic analysis.
      In asphyxiated hearts, the level of isocitrate dehydrogenase and malate
      dehydrogenase was reduced compared to controls. Inverse correlations between the
      level of myocardial malate dehydrogenase and cardiac function were observed in
      the control, but not the H/R hearts. We conclude that reoxygenation of
      asphyxiated newborn piglets reduces the level of myocardial isocitrate
      dehydrogenase and malate dehydrogenase. While the cause is not clear, it may be
      related to the impaired tricarboxylic acid cycle pathway and energy production in
      the heart.

PMID- 18607692
TI  - Insights from soft X-rays: the chlorine and sulfur sub-structures of a
      CK2alpha/DRB complex.
AB  - The diffraction pattern of a protein crystal is normally a product of the
      interference of electromagnetic waves scattered by electrons of the crystalline
      sample. The diffraction pattern undergoes systematic changes in case additionally
      X-ray absorption occurs, meaning if the wavelength of the primary X-ray beam is
      relatively close to the absorption edge of selected elements of the sample. The
      resulting effects are summarized as "anomalous dispersion" and can be always
      observed with "soft" X-rays (wavelength around 2 A) since they match the
      absorption edges of sulfur and chlorine. A particularly useful application of
      this phenomenon is the experimental detection of the sub-structures of the
      anomalous scatterers in protein crystals. We demonstrate this here with a crystal
      of a C-terminally truncated variant of human CK2alpha to which two molecules of
      the inhibitor 5,6-dichloro-1-beta-D-ribo-furanosyl-benzimidazole (DRB) are bound.
      The structure of this co-crystal has been solved recently. For this study we
      measured an additional diffraction data set at a wavelength of 2 A which showed
      strong anomalous dispersion effects. On the basis of these effects we detected
      all sulfur atoms of the protein, the two liganded DRB molecules and a total of 16
      additional chloride ions some of them emerging at positions filled with water
      molecules in previous structure determinations. A number of chloride ions are
      bound to structural and functional important locations fitting to the
      constitutive activity and the acidophilic substrate specificity of the enzyme.

PMID- 18607693
TI  - Effect of ethylenediamine on chemical degradation of insulin aspart in
      pharmaceutical solutions.
AB  - PURPOSE: To examine the effect of different amine compounds on the chemical
      degradation of insulin aspart at pharmaceutical formulation conditions. METHODS:
      Insulin aspart preparations containing amine compounds or phosphate (reference)
      were prepared and the chemical degradation was assessed following storage at 37
      degrees C using chromatographic techniques. Ethylenediamine was examined at
      multiple concentrations and the resulting insulin-ethylenediamine derivates were
      structurally characterized using matrix assisted laser desorption ionization time
      of-flight mass spectroscopy. The effects on ethylenediamine when omitting
      glycerol or phenolic compounds from the formulations were investigated. RESULTS:
      Ethylenediamine was superior in terms of reducing formation of high molecular
      weight protein and insulin aspart related impurities compared to the other amine
      compounds and phosphate. Monotransamidation of insulin aspart in the presence of
      ethylenediamine was observed at all of the six possible Asn/Gln residues with
      Asn(A21) having the highest propensity to react with ethylenediamine. Data from
      formulations studies suggests a dual mechanism of ethylenediamine and a mandatory
      presence of phenolic compounds to obtain the effect. CONCLUSIONS: The formation
      of high molecular weight protein and insulin aspart related impurities was
      reduced by ethylenediamine in a concentration dependant manner.

PMID- 18607694
TI  - New biomaterials as scaffolds for tissue engineering.

PMID- 18607695
TI  - Methods to account for inaccuracies in the dosing history when performing
      population pharmacokinetic analysis.
AB  - PURPOSE: To develop and assess methods to account for missing dose history (MDH).
      METHODS: A simulation study was performed with different doses, dose times and
      formulations using NONMEM. Four methods were used to account for MDH, these were
      the ideal dose method (IDM) which uses the actual dose history, the concentration
      minimum method (CMM) which assumes that the nominal dose history is accurate, the
      extrapolation subtraction method (ESM) which estimates the residual concentration
      at the time of the study dose and the concentration time method (CTM) where the
      time of the previous dose event is estimated. The CTM is a new method. RESULTS:
      The CTM was superior to ESM and CMM and provided parameter estimates that were
      comparable in accuracy to the IDM. CONCLUSIONS: When the nominal dosing history
      is available then the CTM is a simple and effective method to account for
      potential inaccuracies in the dose history.

PMID- 18607696
TI  - Self-perceived musculoskeletal complaints: relationship to time use in women
      homemakers in Hong Kong.
AB  - OBJECTIVE: To examine patterns of time use and self-perceived musculoskeletal
      symptoms for women homemakers in Hong Kong using a cross-sectional survey.
      METHODS: A total of 216 women were selected from a women's center and a selected
      district by trained volunteers for a single interview using convenience sampling;
      63 respondents had paid work and 153 were full-time homemakers. The study
      included a surveillance of self-reported musculoskeletal symptoms for the past 12
      months and a time use log to report respondents' daily activities retrospectively
      during a 24-h reference day. RESULTS: Significant differences were found in the
      mean hours spent in paid work, outdoor activities, and passive leisure between
      respondents with paid and those with unpaid work (P = 0.000-0.021). Although the
      reported musculoskeletal problems were mostly mild to moderate, more than 60% of
      homemakers experienced at least one musculoskeletal symptom over the spine or
      upper or lower extremities in the 12 months prior to the survey. Homemakers were
      more likely to report discomfort in their upper back (OR = 2.70, 95% CI 1.27
      5.71) and shoulder (OR = 3.50, 95% CI 1.21-10.19) while shopping; in their lower
      back (OR = 1.90, 95% CI 1.03-3.50), wrist (OR = 2.02, 95% CI 1.06-3.84), and hip
      (OR = 2.35, 95% CI 1.07-5.13) while washing utensils; and in their finger (OR =
      1.45, 95% CI 1.03-2.03) and knee (OR = 1.84, 95% CI 1.19-2.82) during cleaning
      tasks. CONCLUSION: The results showed a high degree of musculoskeletal discomfort
      among women homemakers in Hong Kong. Modifying current participation in household
      chores like cleaning, washing utensils, and shopping is needed to reduce the risk
      of developing musculoskeletal problems in this population.

PMID- 18607697
TI  - Studies on interaction of CdTe quantum dots with bovine serum albumin using
      fluorescence correlation spectroscopy.
AB  - Luminescent quantum dots (QDs) have widely used in some biological and biomedical
      fields due to their unique and fascinating optical properties, meanwhile the
      interaction of QDs with biomolecules recently attract increasing attention. In
      this paper, we employed fluorescence correlation spectroscopy (FCS) to
      investigate the nonspecific interaction between CdTe QDs and bovine serum albumin
      (BSA) as a model, and evaluate their stoichiometric ratio and association
      constant. Our results documented that BSA was able to bind to CdTe QDs and form
      the QD-BSA complex by a 1:1 stoichiometric ratio. The association constant
      evaluated is 1.06+/-0.14x10(7) M(-1) in 0.01 M phosphate buffer (pH=7.4).
      Furthermore, we found that QD-BSA complex dissociated with increase of ion
      strength, and we speculated that the interaction of CdTe QDs with BSA was mainly
      attributed to electrostatic attraction. Our preliminary results demonstrate that
      fluorescence correlation spectroscopy is an effective tool for investigation of
      the interaction between quantum dots (or nanoparticles) and biomolecules.

PMID- 18607698
TI  - Relationships between alcohol-related informal social control, parental
      monitoring and adolescent problem behaviors among racially diverse urban youth.
AB  - The purpose of the present study is to investigate the relationships between
      alcohol-related informal social control and parental monitoring on alcohol use,
      behavior and intentions; violent behavior; and delinquent behavior in a racially
      diverse population of young urban adolescents. Baseline surveys were administered
      to 6th grade male and female students in 61 urban Chicago schools as part of
      Project Northland Chicago, a group randomized trial for the prevention/reduction
      of substance use. A subset of their parents (n = 3,034) was also surveyed
      regarding alcohol use, violence, and delinquency and related issues. Structural
      equation modeling was used to assess relationships between alcohol-related
      informal social control (as measured by parental perceptions of neighborhood
      action regarding youth drinking) and parental monitoring (as reported by
      parents), and three adolescent outcomes (alcohol use, behaviors and intentions;
      violent behavior; and delinquent behavior; as reported by teens). Associations
      between alcohol-related informal social control and parental monitoring were
      positive and significant (P < .001). Direct paths from parental monitoring to all
      three adolescent outcomes were negative and statistically significant (alcohol
      use, behaviors and intentions, P < .001; violent behavior, P < .001; and
      delinquent behavior, P < .001). Alcohol-related informal social control was not
      significantly associated with adolescent outcomes. Efforts to engage parents to
      be more active in monitoring adolescents' activities may be related to lower
      levels of underage drinking, violence and delinquency among both female and male
      urban youth. Neighborhood norms and action against teenage drinking may be too
      distal to adolescent outcomes to be directly associated.

PMID- 18607700
TI  - Genetic testing of children at risk for adult onset conditions: when is testing
      indicated?
AB  - We report a family with an extensive history of colon cancer consistent with
      hereditary nonpolyposis colorectal cancer (HNPCC). A specific disease causing
      mutation was identified in affected individuals; p.W714X MLH1 mutation. Given the
      very young age of onset of cancer in some affected family members, with the
      youngest affected individual being 19 years of age, genetic counseling was
      recommended to children as young as 9 years. Ethical issues arose when affected
      families requested genetic testing for their underage children. Here we describe
      and debate the value of offering molecular testing for this adult onset disorder
      to several children in this particular family. We also examine possible molecular
      causes for the very young age of onset in some family members.

PMID- 18607701
TI  - The relationship between psychological distress and personality in women from
      families with familial breast/ovarian or hereditary non-polyposis colorectal
      cancer in the absence of demonstrated mutations.
AB  - The aim of this study was to explore associations between mental and cancer
      specific distress (psychological distress) and personality traits in healthy
      women belonging to families with familial cancer and absence of demonstrated
      mutations. We included 238 healthy women from families with familial breast
      ovarian cancer (FBOC) or hereditary non-polyposis colorectal cancer (HNPCC). They
      responded to a questionnaire including validated instruments for psychological
      distress and personality traits. Information on demography and cancer-related
      issues were also collected. Significant associations between psychological
      distress and personality traits were found in these women. The traits of Optimism
      and Harm avoidance showed the strongest association with both types of distress.
      Associations between psychological distress and personality traits were observed
      in women from families with FBOC or HNPCC that fulfilled clinical criteria for
      familial breast/ovarian cancer in the absence of demonstrated mutations.
      Screening for such traits could be helpful in genetic counseling.

PMID- 18607702
TI  - "I wouldn't classify myself as a patient": the importance of a "well-being"
      environment for individuals receiving counseling about familial cancer risk.
AB  - Many individuals receiving genetic counseling are healthy with no need for
      clinical cancer services. We have recently relocated our cancer genetic clinic to
      a small house on the outskirts of a hospital site which incorporates many
      elements proven to be important in creating a "well-being" environment. This
      study explored participants' perceptions of such an environment. Eleven semi
      structured telephone interviews were conducted with women who had attended the
      new cancer genetic clinic. All were at high risk of familial cancer, five were
      gene carriers and three had a personal diagnosis of cancer. The new clinic was
      perceived to be less medical and more relaxing than other clinics, encouraged
      other family members to attend in support of the attendee and did not appear to
      impede information comprehension. The importance of not being made to feel like
      an ill patient was apparent. A desire for a quiet area allowing time for
      reflection whilst waiting for, and following, counseling was identified. A poorly
      designed counseling area could reduce the quality of the interaction between
      patient and counselor. Consideration of specific environmental design features
      may promote individuals' well-being and make those attending genetic counseling
      feel less like "patients." Larger studies should seek to explore further the
      potential associations between factors such as environmental design,
      psychological well-being and comprehension of risk information.

PMID- 18607703
TI  - "What is this genetics, anyway?" Understandings of genetics, illness causality
      and inheritance among British Pakistani users of genetic services.
AB  - Misconceptions about basic genetic concepts and inheritance patterns may be
      widespread in the general population. This paper investigates understandings of
      genetics, illness causality and inheritance among British Pakistanis referred to
      a UK genetics clinic. During participant observation of genetics clinic
      consultations and semi-structured interviews in Urdu or English in respondents'
      homes, we identified an array of environmental, behavioral and spiritual
      understandings of the causes of medical and intellectual problems. Misconceptions
      about the location of genetic information in the body and of genetic mechanisms
      of inheritance were common, reflected the range of everyday theories observed for
      White British patients and included the belief that a child receives more genetic
      material from the father than the mother. Despite some participants'
      conversational use of genetic terminology, some patients had assimilated genetic
      information in ways that conflict with genetic theory with potentially serious
      clinical consequences. Additionally, skepticism of genetic theories of illness
      reflected a rejection of a dominant discourse of genetic risk that stigmatizes
      cousin marriages. Patients referred to genetics clinics may not easily surrender
      their lay or personal theories about the causes of their own or their child's
      condition and their understandings of genetic risk. Genetic counselors may need
      to identify, work with and at times challenge patients' understandings of illness
      causality and inheritance.

PMID- 18607704
TI  - Determinants of the uptake of the full dose of diphtheria-pertussis-tetanus
      vaccines (DPT3) in Northern Nigeria: a multilevel analysis.
AB  - OBJECTIVES: Health behaviors are influenced by an array of factors at the
      individual, household, community and societal levels. This paper examines the
      relative contribution of child's characteristics, mother's attributes, household
      profiles and community factors on the probability that a child will receive the
      full series of diphtheria-pertussis-tetanus vaccines (DPT3) as a proxy for full
      immunization. METHODS: We used data from a 2004 household survey conducted in
      three northern Nigeria states: Borno, Kano and Yobe. We estimated multilevel
      models with fixed effects specified at the individual, household and community
      levels, and random effects at the community level. RESULTS: Overall, only 16.0%
      of the children aged 12-35 months had received DPT3. The data show that a
      significant amount of the variation in DPT3 uptake occurs at the community level.
      The most significant predictors of the uptake of DPT3 are found at multiple
      levels and include child's place of birth, presence of an immunization card,
      mother's ideation, mother's decision-making power and perceived social approval
      of immunization. The data further show that significant community-level
      variations in immunization uptake remain even after individual and household
      factors have been considered. CONCLUSIONS: The data reveal that childhood
      immunization is influenced by norms and unmeasured factors at the community level
      in addition to factors operating at the level of the individual child and the
      household. Strategies for improving the uptake of immunization should include
      culturally appropriate interventions that target multiple levels of influences.
      Improving parental attitudes towards immunization without addressing the issue of
      community norms is not likely to yield significant results.

PMID- 18607705
TI  - Accuracy of body mass index categories based on self-reported height and weight
      among women in the United States.
AB  - OBJECTIVE: The purpose of this study was to assess the accuracy of BMI categories
      based on self-reported height and weight in adult women. METHODS: BMI categories
      from self-reported responses were compared to categories measured during physical
      examination from women, age 18 or older, who participated in the National Health
      and Examination Survey, 1999-2004. We first examined strength of agreement using
      Cohen's kappa, which, unlike sensitivity and specificity, allows for the
      comparison of polychotomous measures beyond chance agreement. Kappa regression
      identifies potential threats to accuracy. Likelihood of bias, as measured by
      under-reporting, was examined using logistic regression. RESULTS: Cohen's kappa
      estimates were 0.443 for pregnant women (N = 724) and 0.705 for non-pregnant
      women (N = 5,910). Kappa varied by age and race, but was largely unrelated to
      socioeconomic status, health and health behaviors. Women who visited a physician
      in the last year or been diagnosed with osteoporosis were more accurate, while
      women most likely to under-report were older, white, non-Hispanic, and college
      educated. CONCLUSIONS: Our results suggest substantial agreement between self
      reported and measured categories, except for women who are pregnant, above the
      age of 75 or without physician visits. Under-reporting may be more prevalent in
      well-educated, white populations than minority populations.

PMID- 18607706
TI  - Effects of caffeic acid phenethyl ester (CAPE) on sepsis in rats.
AB  - Sepsis is still a major cause of the high mortality rate in the intensive care
      unit. Many studies have been published about the severity of sepsis, but the
      cause of mortality in sepsis and multiorgan failure is still obscure. This study
      investigated the effects of caffeic acid phenethyl ester (CAPE) particularly on
      the inflammatory and related histopathological changes in the lung, liver and
      kidney in an experimental sepsis model. Forty Sprague Dawley rats were used in
      this study, and were divided into four groups of ten rats each, as follows: Group
      I was given intraperitoneal saline infusion treatment. Group II was given
      intraperitoneal CAPE infusion treatment. Sepsis was induced in the animals in
      Group III (sepsis with saline infusion), while Group IV rats underwent induced
      sepsis plus CAPE infusion treatment (sepsis with CAPE infusion). Sampling was
      performed 48 h after treatment. The induction of sepsis resulted in a significant
      increase in serum glucose, leukocytes, urea, creatinine, LDH levels in BAL,
      plasma MDA, AST and ALT levels in the sepsis + saline group. The use of CAPE
      significantly decreased these parameters. Histopathological examination revealed
      less congestion, portal inflammation, and focal necrosis of the liver, and less
      congestion, edema, and emphysematous and inflammatory changes in the lung in the
      sepsis + CAPE group than in the other groups. These results support that CAPE may
      be used for the treatment of organ failure during sepsis.

PMID- 18607707
TI  - Studying spike trains using a van Rossum metric with a synapse-like filter.
AB  - Spike trains are unreliable. For example, in the primary sensory areas, spike
      patterns and precise spike times will vary between responses to the same
      stimulus. Nonetheless, information about sensory inputs is communicated in the
      form of spike trains. A challenge in understanding spike trains is to assess the
      significance of individual spikes in encoding information. One approach is to
      define a spike train metric, allowing a distance to be calculated between pairs
      of spike trains. In a good metric, this distance will depend on the information
      the spike trains encode. This method has been used previously to calculate the
      timescale over which the precision of spike times is significant. Here, a new
      metric is constructed based on a simple model of synaptic conductances which
      includes binding site depletion. Including binding site depletion in the metric
      means that a given individual spike has a smaller effect on the distance if it
      occurs soon after other spikes. The metric proves effective at classifying
      neuronal responses by stimuli in the sample data set of electro-physiological
      recordings from the primary auditory area of the zebra finch fore-brain. This
      shows that this is an effective metric for these spike trains suggesting that in
      these spike trains the significance of a spike is modulated by its proximity to
      previous spikes. This modulation is a putative information-coding property of
      spike trains.

PMID- 18607708
TI  - Conversational behaviors in youth with high-functioning ASD and Asperger
      syndrome.
AB  - Twenty-nine youth with autism spectrum disorders and 26 with typical development
      between 12 and 18 years of age were engaged in structured interviews (ADOS). The
      interviews were videotaped and rated for atypical conversational behaviors by
      trained raters, using the Pragmatic Rating Scale (Landa et al. Psychol Med 22:245
      254, 1992). The ASD group was divided into AS and HFA/PDD-NOS subgroups.
      Significant differences were found among groups on approximately one-third of the
      PRS items. These items involved primarily the management of topics and
      information, reciprocity, intonation, and gaze management. The only differences
      to reach significance between the AS and HFA/PDD-NOS group were a greater
      tendency for overly formal speech on the part of the AS group, and more
      difficulty with gaze management on the part of the group with HFA/PDD-NOS. The
      implications of these findings for understanding and treating conversational
      deficits in ASD are discussed.

PMID- 18607709
TI  - Assessing the propensity for sexual coaxing and coercion in relationships: factor
      structure, reliability, and validity of the tactics to obtain sex scale.
AB  - Although there are measures of sexual interest and sexual conflict in romantic
      relationships, none discriminate between sexual coaxing and sexual coercion or
      are sensitive to proximal changes in the propensity to use such strategies. In
      order to study these changes, we developed the Tactics to Obtain Sex Scale (TOSS)
      to assess self-reported likelihood of engaging in sexual coercion and sexual
      coaxing with a romantic partner. In Study 1, a sample of men and women (N = 419)
      in heterosexual relationships completed the TOSS and measures of its predicted
      correlates, including antisociality and mating success. An exploratory factor
      analysis of TOSS scores yielded a two-factor solution. As predicted, the two
      factor solution identified coaxing (COAX) and coercion (COERCE) subscales. There
      was good internal reliability for TOSS, COAX, and COERCE scales (Cronbach alphas
      > .89). Significant correlations between COAX and self-perceived mating success
      and between COERCE and psychopathy provided preliminary evidence of construct
      validity. In Study 2, we replicated the factor structure and established the
      scale as a reliable and valid index of partner sexual coercion and coaxing
      propensity.

PMID- 18607710
TI  - Factorial invariance of child self-report across socioeconomic status groups: a
      multigroup confirmatory factor analysis utilizing the PedsQL 4.0 Generic Core
      Scales.
AB  - The measurement of health-related quality of life (HRQOL) in pediatric medicine
      and health services research has grown significantly over the past decade.
      Socioeconomic status (SES) differences in health outcomes have been extensively
      documented in adult and child populations. In order for HRQOL comparisons to be
      meaningful across different socioeconomic status (SES) groups, items on a HRQOL
      measure must have equivalent meaning across the SES subpopulations being
      compared. That is, they must demonstrate factorial invariance. This study
      examined factorial invariance of child self-report for ages 5-18 across SES
      groups in 453 children utilizing the PedsQL 4.0 Generic Core Scales. Multigroup
      Confirmatory Factor Analysis was performed specifying a five-factor model across
      two SES groups. SES groupings were assigned according to the Hollingshead Index
      of Social Status. Factorial invariance across socioeconomic status 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). The findings support an equivalent five-factor
      structure of child self-report on the PedsQL across the two SES groups studied.
      Based on these data, it can be concluded that children across SES groups
      interpreted items on the PedsQL in a similar manner.

PMID- 18607711
TI  - Influence of acute fluid loading on stress-induced hemoconcentration and
      cardiovascular reactivity.
AB  - The goal of this study was to assess the possible attenuating effects of oral
      fluid loading on hematological and hemodynamic factors during acute psychological
      stress in two separate experiments: Experiment 1 assessed the effects of
      hypotonic fluid loading (water) and Experiment 2 assessed the effects of isotonic
      fluid loading (Gatorade). Twenty-eight participants were recruited for Experiment
      1, and 28 participants were recruited for Experiment 2. Participants for each
      experiment completed two test sessions, once in a hypo-hydrated condition
      (following 12-h fast) and once in a fluid loaded condition (hypotonic or isotonic
      fluid). During each session, hematocrit (Hct), hemoglobin (Hgb), calculated
      plasma volume (CPV), heart rate (HR), systolic blood pressure (SBP), diastolic
      blood pressure (DBP), cardiac output (CO), stroke volume (SV), and total
      peripheral resistance (TPR) were assessed during a 10-min resting baseline
      period, 6-min mental arithmetic (MA) task, and a 16-min recovery period. Results
      for Experiment 1 revealed that the fluid load condition Hct, Hgb, and HR levels
      were significantly lower in comparison to the hypo-hydration condition, and that
      Hct, Hgb, and CPV reactivity was greater during the fluid load condition. Results
      for Experiment 2 revealed that Hct, Hgb, and TPR were lower and CPV, SBP, SV, and
      CO were higher during the fluid load condition compared to the hypo-hydration
      condition and that HR, CO, and TPR reactivity was greater during the fluid load
      condition. Finally, analytic comparisons between the two fluid types revealed
      that SV and CO levels were significantly greater at baseline and during MA when
      isotonic fluid was ingested compared to hypotonic fluid ingestion.

PMID- 18607712
TI  - Chronic nicotine exposure has dissociable behavioural effects on control and
      beta2-/- mice.
AB  - Nicotine exerts beneficial effects on various neurological and psychiatric
      pathologies, yet its effects on cognitive performance remain unclear. Mice
      lacking the beta2 subunit of the nicotinic receptor (beta2-/-) show
      characteristic deficits in executive functions and are suggested as reliable
      animal models for some specific endophenotypes of human pathologies, notably
      ADHD. We use beta2-/- and their controls to investigate the consequences of
      chronic nicotine exposure on cognitive behaviour. We show that in control mice,
      this treatment elicits somewhat slight effects, particularly affecting nocturnal
      activity and self-grooming. By contrast, in beta2-/- mice, chronic nicotine
      treatment had restorative effects on exploratory behaviour in the open-field and
      affected rearing, but did not modify motor functions. We confirmed that beta2-/-
      mice exhibit impaired exploratory and social behaviour, and further demonstrated
      their nocturnal hyperactivity. These data support the proposal that beta2-/- mice
      represent a relevant model for cognitive disorders in humans and that nicotine
      administered chronically at low dose may relieve some of these.

PMID- 18607714
TI  - Cognitive adaptability as a moderator of expressive writing effects in an HIV
      sample.
AB  - This study explored the effects of expressive writing on positive and negative
      outcomes related to perceived psychosocial and health status among persons with
      HIV. This was the first study to examine the moderating effects of cognitive
      adaptability--consisting of dispositional optimism coupled with perceived
      competence--on outcomes of expressive writing. Thirty-seven participants wrote
      about either traumatic experiences or trivial topics in four 20-min sessions.
      Dependent measures obtained at baseline were repeated 1 month later. Although no
      main effects for group were found, baseline levels of cognitive adaptability were
      differentially associated with changes in a positive outcomes index, and a pain
      and physical functioning index in those assigned to the two groups. No moderating
      effects of cognitive adaptability were found for changes in a negative outcomes
      index. Findings underscore the importance of identification of moderating
      variables in understanding the impact of expressive writing interventions among
      individuals with HIV or other conditions.

PMID- 18607713
TI  - Genome scan of a nonword repetition phenotype in families with dyslexia: evidence
      for multiple loci.
AB  - To understand the genetic architecture of dyslexia and identify the locations of
      genes involved, we performed linkage analyses in multigenerational families using
      a phonological memory phenotype--Nonword Repetition (NWR). A genome scan was
      first performed on 438 people from 51 families (DS-1) and linkage was assessed
      using variance components (VC), Bayesian oligogenic (BO), and parametric
      analyses. For replication, the genome scan and analyses were repeated on 693
      people from 93 families (DS-2). For the combined set (DS-C), analyses were
      performed with all three methods in the regions that were identified in both
      samples. In DS-1, regions on chromosomes 4p, 6q, 12p, 17q, and 22q exceeded our
      initial threshold for linkage, with 17q providing a parametric LOD score of 3.2.
      Analysis with DS-2 confirmed the locations on chromosomes 4p and 12p. The
      strongest VC and BO signals in both samples were on chromosome 4p in DS-C, with a
      parametric multipoint LOD(max) of 2.36 for the 4p locus. Our linkage analyses of
      NWR in dyslexia provide suggestive and reproducible evidence for linkage to 4p12
      and 12p in both samples, and significant evidence for linkage to 17q in one of
      the samples. These results warrant further studies of phonological memory and
      chromosomal regions identified here in other datasets.

PMID- 18607715
TI  - Viability of frozen-thawed human embryos with one-two blastomeres lysis.
AB  - OBJECTIVE: To assess the impact of one-two blastomeres lysis on the viability of
      thawed day 3 human embryos. METHODS: A retrospective analysis was performed on
      248 frozen-thawed embryo replacement cycles in which all embryos were frozen at
      day 3 at the seven-eight cell stage with <or=10% fragmentation. RESULTS: Outcomes
      of transfer cycles with fully intact embryos (intact group) were compared with
      those in which all transferred embryos have lost one-two blastomeres (damage
      group). Comparable pregnancy rates (38.46% vs 38.64%), birth rates (34.62% vs
      36.36%) and implantation rates (26.31% vs 26.25%) were obtained in intact and
      damage groups. These results were also not significantly different from mixed
      transfer cycles in which one intact embryo and one damaged embryo were
      transferred together. CONCLUSION: The developmental potential of partially
      damaged cryopreserved human embryos with less than 25% cells loss is comparable
      to that of fully intact embryos. Presence of one-two lysed blastomeres in the
      thawed day 3 embryo does not appear to have a negative influence on the further
      development of the sibling intact cells.

PMID- 18607716
TI  - Predicting early sexual activity with behavior problems exhibited at school entry
      and in early adolescence.
AB  - Youth who initiate sexual intercourse in early adolescence (age 11-14) experience
      multiple risks, including concurrent adjustment problems and unsafe sexual
      practices. The current study tested two models describing the links between
      childhood precursors, early adolescent risk factors, and adolescent sexual
      activity: a cumulative model and a meditational model. A longitudinal sample of
      694 boys and girls from four geographical locations was utilized, with data
      collected from kindergarten through high school. Structural equation models
      revealed that, irrespective of gender or race, high rates of aggressive
      disruptive behaviors and attention problems at school entry increased risk for a
      constellation of problem behaviors in middle school (school maladjustment,
      antisocial activity, and substance use) which, in turn, promoted the early
      initiation of sexual activity. Implications are discussed for developmental
      models of early sexual activity and for prevention programming.

PMID- 18607717
TI  - Beyond the class norm: bullying behavior of popular adolescents and its relation
      to peer acceptance and rejection.
AB  - This study examined to what extent bullying behavior of popular adolescents is
      responsible for whether bullying is more or less likely to be accepted or
      rejected by peers (popularity-norm effect) rather than the behavior of all peers
      (class norm). Specifically, the mean level of bullying by the whole class (class
      norm) was split into behavior of popular adolescents (popularity-norm) and
      behavior of non-popular adolescents (non-popularity-norm), and examined in its
      interaction with individual bullying on peer acceptance and peer rejection. The
      data stem from a peer-nominations subsample of TRAILS, a large population-based
      sample of adolescent boys and girls (N = 3,312). The findings of multilevel
      regression analyses demonstrated that the negative impact of individual bullying
      on peer acceptance and the positive impact on peer rejection were particularly
      weakened by bullying by popular adolescents. These results place the class-norm
      effects found in previous person-group dissimilarity studies in a different
      light, suggesting that particularly bullying by popular adolescents is related to
      the social status attached to bullying.

PMID- 18607718
TI  - Common and unique factors associated with DSM-IV-TR internalizing disorders in
      children.
AB  - With the fifth edition of the Diagnostic and Statistical Manual of Mental
      Disorders (American Psychiatric Association. Diagnostic and statistical manual of
      mental disorders DSM-IV Fourth Edition-Text Revision. Author, Washington, DC.
      2000) ahead, decisions will be made about the future of taxonomic
      conceptualizations. This study examined the factor structure of items from three
      internalizing disorders (Social Phobia, Generalized Anxiety Disorder, and
      Depression) on the Anxiety Disorders Interview Schedule for DSM-IV-Child Version
      (Silverman, W. K., & Albano, A. M. Anxiety disorders interview schedule for
      children for DSM-IV, child and parent versions. Psychological Corporation, San
      Antonio, 1996). Two-, three-, and four-factor models emerged in an exploratory
      factor analysis. Confirmatory factor analysis provided additional empirical
      support for the four-factor model over the two- or three-factor models.
      Implications for the structure of the DSM-V taxonomy in children and adolescents
      are discussed.

PMID- 18607719
TI  - Differential effects of strategic planning on community change in two urban
      neighborhood coalitions.
AB  - Community coalitions represent a promising approach for addressing the
      interrelated and multiply- determined issues affecting urban neighborhoods of
      concentrated poverty. The literature suggests a number of community processes
      that may affect coalition efforts to change and improve communities. This study
      uses an interrupted time-series design to examine the effects of a strategic
      planning intervention on community change in two urban neighborhoods in the
      Kansas City metropolitan area. Results showed that strategic planning was
      associated with increased rates of community change in the two urban neighborhood
      coalitions. Under appropriate conditions, such as the presence of consistent
      leadership, strategic planning may be a particularly effective mechanism for
      stimulating community change and addressing locally-determined goals in urban
      neighborhoods.

PMID- 18607720
TI  - The effect of residential neighborhood on child behavior problems in first grade.
AB  - Child behavior problems have been identified as being responsible for the
      greatest reduction in quality of life for children between ages 1 and 19. In this
      study, we examine whether neighborhood social processes are associated with
      differences in child behavior problems in an economically and racially diverse
      sample of 405 urban-dwelling first grade children and whether parenting behavior
      mediates and/or moderates the effects of neighborhoods. Furthermore, we examine
      whether neighborhood social processes play the same role with regards to child
      behavior problems at differing levels of neighborhood economic impoverishment.
      Results of multivariate multilevel regression analyses indicate that a high
      negative social climate is associated with greater internalizing problems. High
      potential for community involvement for children in the neighborhood was
      associated with fewer behavior problems, but only in economically impoverished
      neighborhoods. Differences in parenting behavior did not appear to mediate
      neighborhood effects on behavior problems, and parenting characterized by a high
      degree of positive involvement was associated with fewer behavior problems in all
      types of neighborhoods.

PMID- 18607721
TI  - Core saccharide dependence of sialyl Lewis X biosynthesis.
AB  - The sialyl-Lewis X (SLe(x)) determinant is important in leukocyte extravasation,
      metastasis and bacterial adhesion. The role of the protein, N-glycan and O-glycan
      core structures for the biosynthesis of SLe(x) in vivo by fucosyltransferases
      (FucTs) is not known. Immunoglobulin G (IgG) Fc fusion proteins of alpha(1)-acid
      glycoprotein (AGP), P-selectin glycoprotein ligand-1 (PSGL-1) or CD43 were used
      to probe the specificity of FucT-III-VII expressed alone in 293T and COS cells or
      together with O-glycan core enzymes in Chinese hamster ovary (CHO)-K1 cells.
      Western blotting with the monoclonal antibodies CSLEX and KM93 showed that FucT
      III and V-VII produced SLe(x) on core 2 in CHO cells. Only FucT-V, -VI and, with
      low activity, -VII worked on core 3 on CD43/IgG, but no SLe(x) was detected with
      CSLEX on PSGL-1/IgG with core 3. KM93 stained SLe(x) on core 2, but was not
      reactive with SLe(x) on core 3. FucT-III, V-VII made SLe(x) on N-glycans of
      AGP/IgG in CHO, but not in COS and 293T cells, even though the same FucTs could
      make SLe(x) on CD43/IgG and PSGL-1/IgG in these cells. Our results define the
      specificities of FucT-III-VII in SLe(x) biosynthesis on O-glycans with different
      core structures and the fine specificity of the widely used anti-SLe(x)
      monoclonal antibody, KM93.

PMID- 18607722
TI  - Brainstem concentrations of cholesterol are not influenced by genetic ablation of
      the low-density lipoprotein receptor.
AB  - PURPOSE: The low-density lipoprotein receptor (LDLr) mediates the uptake of LDL
      particles enriched with cholesterol, into several tissues. In contrast to other
      tissues, the brain is thought to obtain cholesterol solely by de novo synthesis,
      yet certain brain regions such as the brainstem are highly enriched with the
      LDLr. The goal of the present study was to assess the role of the LDLr in
      maintaining cholesterol concentrations in the brainstem of wildtype and LDLr
      knockout (LDLr-/-) mice. Cholesterol concentrations were also measured in the
      cortex, which served as a reference point, due to the lower expression of the
      LDLr, as compared to the brainstem. METHODS: LDLr-/- and wildtype mice consumed
      an AIN-93G diet ad libitum until 7 weeks of age. After microwaving, the cortex
      and anterior brain stem were isolated for cholesterol analysis. Cholesterol was
      extracted into chloroform/methanol, derivatized in trimethylsilyl chloride and
      measured by gas chromatography/mass spectrometry. RESULTS: Concentrations of
      cholesterol in the brainstem did not differ statistically between LDLr-/- (18.8
      +/- 1.6 mg/g wet weight brain) and wildtype (19.1 +/- 2.0). Cortical cholesterol
      concentrations also did not differ statistically between LDLr-/- (11.0 +/- 0.4
      mg/g wet weight brain) and wildtype (11.1 +/- 0.2) mice. CONCLUSION: The LDLr is
      not necessary for maintaining cholesterol concentrations in the cortex or
      brainstem, suggesting that other mechanisms are sufficient to maintain brain
      cholesterol concentrations.

PMID- 18607725
TI  - Principles and analysis of hematopoietic stem cell transplantation outcomes: the
      physician's perspective.
AB  - Hematopoietic stem cell transplantation (HSCT) is used widely for the treatment
      of malignant and non-malignant diseases. Advances in transplantation strategies
      such as modifications to existing transplant-conditioning regimens to lower
      morbidity and mortality, use of alternative donors and grafts, supportive care
      including graft-versus-host disease prophylaxis and antimicrobial therapy have
      led to increasing numbers of HSCT being performed. The procedure is now available
      to children, young and older adults with an ever increasing number of survivors
      from this procedure. Analysis of outcomes after HSCT giving consideration to
      existing strategies warrants using appropriate statistical methodology. This is
      critical not only in documenting the current success of HSCT but to plan future
      strategies to optimize accessibility to HSCT, donor and graft choices, patient
      selection, counsel potential HSCT candidates and long-term survivors and plan
      intervention trials for these persons. We describe concepts and principles of
      HSCT to better understand the complexities associated with outcome analysis.

PMID- 18607726
TI  - Efficacy of a randomized trial of a community and school-based anti-violence
      media intervention among small-town middle school youth.
AB  - In a community randomized controlled trial, intervention middle school students
      from small towns were exposed to a community and school-based anti-violence
      intervention ("Resolve It, Solve It"). The primary intervention was a media
      campaign in which local high school students served as models in print, radio,
      and television PSAs and spearheaded local school and community activities. The
      media campaign was supported with school and community events that reinforced
      campaign messages. Tests of recognition and recall indicated widespread exposure
      to the media intervention. Multiple group latent growth models indicated that
      relative to control students, intervention students reported significant
      differences in rates of growth for intent for violence, physical assault against
      people, verbal victimization, and perceived safety at school. No differences were
      found for verbal assault, physical assault against objects, physical
      victimization, or self-efficacy for avoiding violence. When examined by sex, it
      was determined that results for physical assault against people were obtained
      only among female students, and changes in verbal victimization and perceived
      school safety were observed only among male students. These results suggest that
      a media and reinforcing community intervention led by older peers can alter rates
      of growth for some measures of violence and associated factors among small-town
      youth. Further research is indicated to determine how different campaign messages
      influence students by sex.

PMID- 18607727
TI  - Anthropometric characteristics of Pakistani school children living in Bahrain.
AB  - BACKGROUND: This survey was designed to study the gender difference in physical
      growth of 1113 Pakistani children (646 male and 467 female) living in Bahrain and
      to compare growth with their Bahraini and Pakistani counterparts. METHODS:
      Measurements of height, weight, mid-arm circumference, biceps, triceps,
      subscapular and suprailiac skinfold thickness were carried out using the standard
      methods, and the median values for height and weight were plotted against the
      National Center for Health Statistics (NCHS) standard charts. RESULTS: The median
      weight of the boys was below the 25th percentile rising slightly above the 25th
      percentile at 12 years. The median height was also below the 25th percentile
      touching the 25th percentile only between 10-12 and 17 years. In girls, the
      median weight touched the 50th percentile at 15 years, followed by a fall to the
      5th percentile between 16 and 17 years of age while the median height touched the
      5th percentile at 17 years of age. The median body mass index (BMI) values were
      above the 50th percentile between 13 and 15 years in boys, and below the 50th
      percentile at all ages in girls. The median triceps skinfold thickness in boys
      was above the 50th percentile between 10-15 and 17 years in boys and in girls it
      was mostly below the 50th percentile rising above 50th percentile at 14, 15 and
      17 years of age. CONCLUSION: The height and weight of the study group was similar
      to that of children residing in Pakistan for both the genders, but lower than
      their Bahraini counterparts for most age groups compared. Furthermore, Pakistani
      boys residing in Bahrain were taller after 14 years of age and heavier after 16
      years of age compared to their female counterparts.

PMID- 18607728
TI  - Why are Korean American physicians reluctant to recommend colorectal cancer
      screening to Korean American patients? Exploratory interview findings.
AB  - BACKGROUND: Korean Americans have one of the lowest screening rates for
      colorectal cancer. Although physician recommendation is one of the most important
      predictors of cancer screening across populations, only few Korean American
      patients receive such a recommendation. METHODS: We interviewed 14 Korean
      American physicians in Los Angeles area who primarily serve Korean Americans to
      explore why they are reluctant to recommend colorectal cancer screening to their
      Korean patients. RESULTS: Physicians identified barriers attributable to
      themselves (i.e., lack of knowledge, fear of medicolegal liability), their
      patients (i.e., patient's unfamiliarity with the concept of screening), and the
      health care system (i.e., lack of referral network, poor reimbursement).
      DISCUSSION: Our results suggest the need for multi-faceted interventions directed
      at the physicians, their patients, and the health care system. Further research
      is needed to validate our results and to assess the extent to which they apply to
      physicians from other racial/ethnic groups.

PMID- 18607729
TI  - Association between anxiety and smoking in a sample of urban black men.
AB  - BACKGROUND: Anxiety and smoking associations have been examined previously, but
      not in high risk populations of smokers, such as black males, who bear an excess
      burden of smoking-related illnesses. METHODS: This study assessed the relation
      between self-reported smoking status and anxiety using data collected by
      structured telephone interviews with a sample of 430 black, middle-aged males
      participating in an ongoing cancer prevention trial. RESULTS: There was a
      significant association between anxiety caseness and smoking (p = .006), with
      more probable cases among current smokers. A priori t-tests showed that current
      smokers had greater anxiety than former and nonsmokers (p's = 0.02). Among
      current smokers, greater anxiety was associated with heavier smoking (p = .008),
      an association not present among former smokers. DISCUSSION: This study could
      guide future experimental studies examining smoking-anxiety associations and
      inform intervention strategies addressing anxiety in underserved nicotine
      dependent populations with high tobacco-related risks.

PMID- 18607730
TI  - One-trial visual recognition in cats: the role of the rhinal cortex.
AB  - Memory for visual recognition in primates is at least partially mediated by the
      peripheral and entorhinal (i.e., rhinal) areas of the cerebral cortex. The roles
      of these structures in visual recognition in cats was studied by producing
      electrolytic combined lesions of the rhinal (perirhinal + entorhinal) areas in a
      group of cats trained in a modified Wisconsin test apparatus to delayed selection
      of an object on the basis of its image on presentation of a new object in every
      trial in the test. Control groups consisted of intact and sham-operated cats.
      Animals with rhinal lesions were no different from sham-operated and intact
      animals in the initial training to the rules for correct responding to the
      objects presented; they also showed no difference at the minimum delay period of
      5 sec used in these experiments. However, a statistically significant difference
      was seen on testing with a delay of 10 sec, demonstrating impairment of intrinsic
      visual recognition memory.

PMID- 18607731
TI  - Role of the motor cortex in the rearrangement of a natural movement coordination
      in dogs.
AB  - Chronic experiments on dogs were performed to study the activity of the shoulder
      muscles involved in elevating the forelimb used by the animal to lift a food
      containing cup and keep it elevated during eating. At the early stage of
      acquisition of this operant reaction, limb-lifting occurred with an anticipatory
      upward head movement; lowering of the head to the feeder was associated with
      lowering of the lifted limb. The new coordination required for food to be
      obtained, i.e., maintaining the elevated limb in a posture with the head lowered,
      could only be achieved as a result of learning. In untrained dogs with the
      natural coordination, elevation of the limb occurred with activation of the
      deltoid and teres major muscles, teres minor being active on standing but ceasing
      its activity before limb elevation. During training the activity of the teres
      minor muscle changed to the opposite pattern. Limb elevation in the learned
      coordination was accompanied by activation of all three shoulder flexors.
      Lesioning of the motor cortex in the projection area of the "working" limb, but
      not in other areas, led to impairments of the acquired coordination and a new
      pattern of shoulder muscle activity. These data led to the conclusion that
      rearrangement of the initial coordination was linked with the formation of a new
      means of elevating the limb in which the muscle pattern was supported by the
      motor cortex.

PMID- 18607732
TI  - Involvement of angiotensin II and angiotensin IV in producing the individual
      characteristics of defensive and feeding behavior in rats.
AB  - The involvement of angiotensin II and angiotensin IV in defensive (the tail-flick
      test) and acquired feeding behavior in rats was studied. Angiotensin II had a
      greater role than angiotensin IV in feeding behavior in rats. Angiotensin IV had
      a greater effect than angiotensin II on the defensive behavior of individuals.
      Individual differences in animal behavior were identified.

PMID- 18607734
TI  - Dynamics of repair regeneration of rat cutaneous nerves after traumas of
      different severity.
AB  - Studies on 163 mongrels with experimental crush trauma to cutaneous nerves
      addressed the dynamics of regeneration over a period of 10-50 days post-trauma.
      Two series of experiments were performed, in which a cutaneous nerve (the
      saphenous nerve) was crushed with a hemostatic clamp over lengths of 2 and 4 mm,
      respectively. Destructive processes in the L3 and L4 spinal ganglia, increases in
      the numbers of myelin fibers in the nerve distal to the trauma site and the rate
      of growth of the damaged nerve fibers towards the skin after nerve traumas of
      different lengths, recorded at 10-50 days, were identical in the two series. The
      rate of myelinization of regenerating fibers after 2-mm crush lesions was greater
      than that seen after 4-mm crush injuries only in the period up to 30 days post
      trauma.

PMID- 18607733
TI  - Effects of the GABA receptor agonist phenibut on behavior and respiration in
      rabbits in emotionally negative situations.
AB  - Three groups of rabbits differing in terms of movement activity in an open field
      (active, passive, and intermediate animals) were used to study the effects of
      systemic administration of the GABA receptor agonist phenibut (40 mg/kg, s.c.) on
      behavior in the open field, behavioral reactivity, and changes in measures of
      respiration during exposure to emotionally negative stimuli. Phenibut
      administration led to decreases in horizontal movement activity and some elements
      of investigative behavior in rabbits in the open field, along with decreases in
      the reactivity of the animals to emotionally significant stimuli. There were
      reductions in the probabilities of both active (orientational-investigative,
      active defensive) and passive defensive (freezing) reactions. The effects of
      phenibut depended on the typological characteristics of the rabbits: its actions
      on behavior were most marked in active rabbits and were less marked in passive
      animals; phenibut had virtually no effect on the behavior of intermediate
      rabbits. The duration of inhalation by the rabbits on exposure to emotionally
      significant stimuli increased after phenibut, which contrasted with a reduction
      seen in normal animals; this is evidence for changes in the autonomic reactivity
      of the animals.

PMID- 18607735
TI  - Structural organization of the zona incerta of the dog diencephalon.
AB  - Studies performed using the Nissl and Kluver-Barrera methods for analysis of the
      organization of fibers, morphological neuron types, and neuron density
      distribution were undertaken to map the zona incerta of the diencephalon of the
      dog brain; five individual sectors were identified, whose boundaries were further
      identified by histochemical detection of NADPH-diaphorase-positive neurons.

PMID- 18607736
TI  - Interaction of the postsynaptic effects of glycine and GABA on spinal cord
      neurons in the frog Rana temporaria.
AB  - Studies were performed on mechanically isolated spinal cord multipolar cells
      (presumptive motoneurons) from the frog Rana temporaria using patch-clamp methods
      in the whole-cell configuration. These experiments showed that the amplitudes of
      transmembrane currents arising in response to simultaneous application of GABA
      and glycine were smaller than the sums of the amplitudes of the responses of the
      same neurons to GABA and glycine applied individually. Investigation of the
      mechanisms of this occlusion showed that superfusion of neurons with glycine
      solution (0.2 mM) resulted in complete blockade of responses to application of
      GABA (5 mM) and vice versa. This phenomenon may have resulted from cross-blockade
      associated with the existence of a single receptor complex sensitive to both GABA
      and glycine and from the interaction of GABA and glycine receptors.

PMID- 18607737
TI  - Efferent innervation of the cervical segment of the trachea in early postnatal
      ontogenesis.
AB  - A method based on retrograde axonal transport of horseradish peroxidase was used
      to study the efferent innervation of the cervical segment of the trachea in
      neonatal kittens and kittens aged 10, 20, and 30 days and two months. Labeled
      neurons in all animals were located in the cranial cervical, middle cervical, and
      cervicothoracic sympathetic ganglia on the right and left sides, at the level of
      the medulla oblongata, and in the dorsal and ambiguus nuclei of the vagus nerves.
      Up to age 30 days, neurons were also seen in the ventral horns of the spinal cord
      in segments C1 to C5. The number of sympathetic neurons innervating the trachea
      increased from the moment of birth, reaching a maximum by 10-20 days and then
      decreasing to age two months. The number of parasympathetic neurons gradually
      decreased during ontogenesis.

PMID- 18607739
TI  - Typological features in the behavior of rats.
AB  - The existence of internal relationships between measures of investigative and
      seeking types of activity and the level of anxiety was demonstrated in rats.
      Individual measures of investigative activity and levels of anxiety were measured
      using classical methods-the open field test and the elevated plus maze test. The
      productivity of directed seeking activity was studied using methods developed by
      ourselves in a universal problem-solving box. Cluster analysis demonstrated
      hierarchical groups in the population with similar quantitative-qualitative
      behavioral characteristics.

PMID- 18607738
TI  - Vasopressinergic neurons in rats in ontogenesis: responses to salt loading and
      their modulation by noradrenergic afferents.
AB  - Salt loading in adult mammals leads to increased vasopressin secretion by
      vasopressinergic neurons in the supraoptic nucleus, which is mediated by the
      actions of a number of hormones and neurotransmitters, including noradrenaline.
      The present study addressed identification of the stage of ontogenesis at which
      vasopressinergic neurons start to respond to salt loading and when the
      noradrenalinergic regulation of this process begins. Studies were performed on
      rats at embryonic day 21 (E21), postnatal day 3 (P3), and postnatal day 13 (P13)
      using immunocytochemical and in situ hybridization. Animals were subjected to
      salt loading, in some cases on the background of the alpha1-adrenoceptor
      inhibitor prazosin. Salt loading in rats of all age groups induced increases in
      the synthesis of vasopressin mRNA, probably accompanied by increased synthesis of
      vasopressin peptide. At E21 and P3, intraneuronal vasopressin levels were
      increased; there was no change at P13. In salt loading on the background of
      prazosin administration, vasopressin mRNA and vasopressin contents at E21 showed
      no change, while at P3 they were increased, which is evidence of the inhibitory
      effect of noradrenaline on vasopressin expression in the early postnatal period.
      Thus, vasopressinergic neurons start to respond to salt loading at the end of the
      prenatal period with increases in vasopressin expression; noradrenergic afferents
      have inhibitory influences on vasopressin expression in the early postnatal
      period.

PMID- 18607740
TI  - Comparative analysis of the EEG in babies in the first month of life with
      gestation periods of 30-42 weeks.
AB  - The aim of the present work was to compare measures of the power spectra,
      indexes, and coherence of the EEG in term and preterm infants in the first month
      of life. Six groups of children were investigated, born at 1) 30-32, 2) 33-34, 3)
      35-36, 4) 37-38, 5) 39-40, and 6) 41-42 weeks of gestation; there were 10 in each
      group. The power of the delta frequencies was maximal in group 5. The power of
      theta frequencies was greatest in group 3. The theta frequencies index was higher
      in groups 2, 3, and 4. Alpha frequency power was greater in group 2. The index of
      alpha frequencies was greater in groups 1, 2, and 3. The indexes of beta1 and
      beta2 frequencies was greater in groups 1, 2, and 4. The largest number of
      coherence links in the delta, theta, and alpha frequencies were seen in group 6.
      Group 2, as compared with group 5, had more coherence links in the delta
      frequencies in the posterior and posterocentral areas, as well as more
      intrahemisphere synchronization in the theta and alpha frequencies. The results
      obtained here showed that EEG power spectra, indexes, and coherence depended on
      the gestation age at the time of birth, though this relationship was nonlinear.

PMID- 18607741
TI  - Optical-geometrical characteristics of fragmented figures and integral perception
      thresholds in repeated tests.
AB  - The causes of reductions in the integral perception threshold for fragmented
      figures in repeat trials using the Gollin test were investigated. The first study
      involved four trials with 5-day intervals using one set of figures. The amplitude
      frequency characteristics of the test stimuli were interpreted using correlation
      analysis, as were the thresholds in each trial. The second study involved two
      trials with a three-day interval. On repeat testing, half of the figures were
      known (from the first test) to the subjects. In addition, half of the figures
      (both familiar and unfamiliar) were fragmented such that their amplitude
      frequency characteristics had values similar to those in the first test. The
      results showed that the decrease in thresholds were mainly due to optimization of
      the functioning of the mechanisms operating with the statistical rather than the
      subject characteristics of the images.

PMID- 18607742
TI  - Clinical-psychophysiological studies of patients with panic attacks with and
      without agoraphobic disorders.
AB  - A total of 77 patients with panic attacks (PA) with and without agoraphobic
      disorders were studied, along with 28 healthy subjects. Use of clinical
      neurological investigation methods was supplemented by psychological methods, EEG
      recordings, and auditory event-linked evoked potentials (EP). Patients with PA
      with agoraphobic disorders were found to be characterized by significant
      decreases in the power density of the alpha rhythm and increases in the power
      density of the beta rhythm in the right hemisphere, reflecting significant
      activation of the ascending mesencephalic reticular formation; the most
      characteristic feature in patients without agoraphobia was a significant increase
      in the power density of the theta rhythm in the temporal areas of the right
      hemisphere, reflecting increased activity in temporal-limbic structures. Patients
      with agoraphobia had lower EP P300 peak amplitudes, with more significant
      impairments to habituation, and more marked impairments of attention and higher
      levels of anxiety and depression as compared with patients without agoraphobia.

PMID- 18607743
TI  - Use of the principle of proprioceptive correction in the restoration of voluntary
      movements in the paralyzed arm in patients in the late recovery and residual post
      stroke periods.
AB  - A specially developed proprioceptive correction costume was used for the
      restoration of motor functions in the proximal parts of the upper limb in central
      paralysis syndrome in patients in the late recovery and residual post-stroke
      states. The costume is a logical continuation of the Adeli and Gravistat
      proprioceptive correction systems, directed to restoring balance and gait in post
      stroke patients. The costume consists of a waistcoat and cuffs connected by a
      system of elastic bands fixed around the shoulder and forearm of the paralyzed
      upper limb. Controlling the tension in the elastic bands allows a regime of
      "facilitated" work to be created, with increased loading of active movements in
      the proximal parts of the paralyzed arm. The effectiveness of using the
      proprioceptive correction costume in restoring voluntary movements in the upper
      limb was demonstrated during the treatment of 23 patients in the late recovery
      and residual post-stroke periods. In most patients, treatment resulted in
      significant decreases in the extent of paralysis in the arm and produced recovery
      rates greater than those seen in the control group. Use of the proprioceptive
      correction costume in the neurorehabilitation complex is advised for restoration
      of voluntary movements in the arms of stroke patients.

PMID- 18607744
TI  - Effects of cerebrolysin on moderate cognitive impairments in cerebral vascular
      insufficiency (a clinical-electrophysiological study).
AB  - The efficacy of treatment with cerebrolysin was studied in 40 patients with
      cerebral vascular insufficiency. Cerebrolysin (20 daily i.v. infusions of 10 ml
      in 200 ml of physiological saline) was found to be an effective means of treating
      this group of patients. Courses of cerebrolysin treatment decreased the severity
      of memory and attention impairments, improving the overall cognitive status of
      the patients. Clinical observations and neuropsychological testing were supported
      by electrophysiological results, in terms of the P300 cognitive evoked potential.
      The effects of treatment at the doses used here were delayed and were seen three
      months after completion of treatment.

PMID- 18607745
TI  - Changes in EEG spectral power on perception of neutral and emotional words in
      patients with schizophrenia, their relatives, and healthy subjects from the
      general population.
AB  - EEG correlates of impairments in the processing of emotiogenic information which
      might reflect a genetic predisposition to schizophrenia were sought by studying
      the dynamics of EEG rhythm powers on presentation of neutral and emotional words
      in 36 patients with schizophrenia, 50 of their unaffected first-degree relatives,
      and 47 healthy subjects without any inherited predisposition to psychoses. In
      controls, passive hearing of neutral words produced minimal changes in cortical
      rhythms, predominantly in the form of increases in the power levels of slow and
      fast waves, while perception of emotional words was accompanied by generalized
      reductions in the power of the alpha and beta(1) rhythms and regionally specific
      suppression of theta and beta(2) activity. Patients and their relatives
      demonstrated reductions in power of alpha and beta(1) activity, with an increase
      in delta power on hearing both groups of words. Thus, differences in responses to
      neutral and emotional words in patients and their relatives were weaker, because
      of increased reactions to neutral words. These results may identify EEG
      reflections of pathology of involuntary attention, which is familial and,
      evidently, inherited in nature. No reduction in reactions to emotiogenic stimuli
      was seen in patients' families.

PMID- 18607746
TI  - Reflection of the effectiveness of heterosensory integration in measures of event
      linked potentials.
AB  - The phenomenon of bimodal event-linked potential mismatch and summation of
      unimodal responses were used to study the relationship between mismatch amplitude
      and the effectiveness of visual-auditory integration. The effectiveness of
      integration was assessed in terms of the extent to which experimental measures
      approached the parameters of the "ideal observer." The greater the effectiveness
      of integration, the greater the focus of mismatch shifted from the occipital to
      the frontal areas of the cortex. The greatest correlation between mismatch
      amplitude and the effectiveness of visual-auditory integration was seen in the
      left frontal cortex.

PMID- 18607747
TI  - Serotoninergic mechanisms of the effects of neurotensin on passive avoidance
      behavior in rats.
AB  - The aim of the present work was to identify the features of the actions of
      neurotensin on administration into the substantia nigra or dorsal cervical
      nucleus on the reproduction of passive avoidance reactions in rats. The results
      showed that the action of neurotensin administered into the substantia nigra was
      accompanied by sharp reductions in passive avoidance reactions, while
      administration into the dorsal cervical nucleus, conversely, led to increases in
      these reactions and slowing of their extinction. The effects of microinjections
      of the serotonin 5-HT(1A) receptor agonist 8-hydroxydipropylaminotetraline (8-OH
      DPAT) into these brain structures were analogous to the effects of neurotensin.
      The different behavioral effects of administration of neurotensin corresponded to
      identifiable changes in the levels of serotonin and its metabolite 5
      hydroxyindoleacetic acid in the caudate nuclei of the brain. These data led to
      the conclusion that the effects of neurotensin on passive avoidance behavior are
      associated with the regulation of the emotional state of the animals via actions
      on the functions of brain serotoninergic structures.

PMID- 18607748
TI  - Some features of learning in the Morris water test in rats selected for responses
      to humans.
AB  - The characteristics of learning in the Morris water test were studied in gray
      rats subjected to prolonged selection for elimination (the tame strain) and
      enhanced (the aggressive strain) aggressivity towards humans. Blood
      corticosterone levels at different stages of learning were also estimated. Tame
      rats learned to locate the invisible platform better than aggressive rats. The
      time spent seeking the platform by aggressive rats increased because they spent
      more time at the periphery of the basin. The duration of vertical investigative
      activity while on the platform was greater in tame rats than in aggressive rats.
      Fixation of the memory trace was demonstrated by the observation that rats of
      both strains spent more time in the sector in which the platform had been located
      during the training period. Rats of the two strains showed essentially no
      difference in terms of the time spent seeking the platform when it was placed in
      the opposite sector. After one day of training, blood corticosterone was
      significantly lower in tame than in aggressive rats. On subsequent training days,
      hormone levels in tame animals increased and were no different from those in
      aggressive rats. It is suggested that decreased emotionality and stress
      reactivity facilitated the learning process in tame rats in the Morris water
      test.

PMID- 18607749
TI  - Clinical-epidemiological characteristics of mental disturbances comorbid with
      somatic pathology in patients attending a regional polyclinic.

PMID- 18607750
TI  - The role of serotonin in the pathogenesis and clinical presentations of migraine
      attacks.
AB  - The Fontana-Masson method was used in 63 migraine patients to stain peripheral
      blood thrombocytes and measure the numbers of serotonin granules within them
      during the interictal period and, in 33 patients, during and 24, 48, and 72 h
      after migraine attacks. Enzyme-linked immunosorbent assay (ELISA) was used in 19
      patients during attacks to study dissolved serotonin concentrations in serum.
      During the interictal period, high contents of serotonin granules per 100 blood
      thrombocytes were found (469.3 +/- 22.4), which was not significantly different
      from the level in healthy subjects (447.9 +/- 19.6). At the peak of attacks,
      serotonin contents decreased to 47.7 +/- 7.4, while the dissolved serotonin
      concentration, conversely, increased to 345.5 +/- 39.1 ng/ml (compared with serum
      serotonin levels of 184.2 +/- 12.3 ng/ml in healthy subjects). During the first
      and subsequent time points after migraine attacks, thrombocyte serotonin levels
      returned to baseline. These data provide evidence of impairment of serotonin
      stored in thrombocytes during migraine attacks and its release into the plasma,
      which may provide a laboratory method for monitoring the development of migraine
      attacks.

PMID- 18607751
TI  - Oxygen tension in rat cerebral cortex microvessels in acute anemia.
AB  - Polarigraphic microelectrodes were used to study the distribution of oxygen
      tension (pO(2)) in arterioles (lumen diameters 8-80 microm) and venules (lumen
      diameters 8-120 microm) in the rat cerebral cortex during acute reductions in
      blood hemoglobin ([Hb]). Isovolumic hemodilution with 5% albumin solution was
      performed in steps from an initial [Hb] of 14.1 +/- 0.3 g/dl (control) to 9.8 +/-
      0.3 g/dl (step 1), 6.6 +/- 0.4 g/dl (step 2), and 4.6 +/- 0.3 g/dl (step 3). Mild
      anemia (step 1, hematocrit 30%) led to an increase in pO(2) in the arterial side
      of the microcirculatory bed, with virtually no change in pO(2) in the venous
      side. Step 2 (hematocrit 20%) was accompanied by a further insignificant increase
      in pO(2) in arterioles, while there was a significant reduction (on average to 32
      mmHg) in venules. Step 3 (hematocrit 13-14%) led to a (statistically
      insignificant) increase in pO(2) in arterioles. pO(2) in venules decreased, on
      average, to 27 mmHg; the proportion of smallest venules with low pO(2) values
      (less than 20 mmHg) increased to 31% (from 3% in controls). In some capillaries,
      pO(2) was 5-10 mmHg, which was an indicator of the presence of hypoxic zones in
      brain tissues. These zones primarily arose close to the smallest capillary and
      venous microvessels, with slowed or impaired blood flow.

PMID- 18607752
TI  - Glutamatergic regulation of extracellular citrulline levels in the nucleus
      accumbens during an emotional conditioned reflex.
AB  - Intracerebral microdialysis and high-performance liquid chromatography were used
      to demonstrate that the acquisition and execution of an emotional conditioned
      reflex in Sprague-Dawley rats are accompanied by increases in extracellular
      citrulline (a co-product of nitric oxide synthesis) levels in the nucleus
      accumbens. Injection of the selective NMDA glutamate receptor antagonist MK-801
      (100 microM) into the nucleus accumbens significantly decreased the increase in
      extracellular citrulline seen in this structure on acquisition of the emotional
      conditioned reflex and completely blocked the increase induced by execution of
      the reflex. These data suggest that during the acquisition and execution of an
      emotional conditioned reflex, the glutamatergic input of the nucleus accumbens
      acts on NMDA receptors to stimulate nitric oxide production in this part of the
      brain.

PMID- 18607753
TI  - Discrimination of the spectral structures of sound signals on the background of
      interference.
AB  - Presentation of test signals consisting of sounds with rippled spectra allowed
      measurements of the frequency-resolving ability (FRA) of hearing to be performed
      in humans without using frequency-dependent masking techniques. This allowed
      studies of changes in FRA in the presence of noise interference. In conditions of
      diotic presentation (to both ears in parallel) of the test signal and noise, FRA
      decreased significantly if the interference frequency was lower or equal to the
      test signal frequency. The relationship between this effect and the sound
      intensity and noise:signal ratio varied for low-frequency noise and for noise at
      the same frequency as the test signal, which indicates that these two types of
      interference have different mechanisms. However, in both cases, noise of
      sufficient intensity led to a complete inability to discriminate the fine
      spectral structure of the test signal. In dichotic presentation (test signal to
      one ear, noise to the other), noise had virtually no effect on FRA over a wide
      range of test signal and noise frequencies and noise:signal ratios. Thus, there
      was essentially complete dichotic release of FRA from the effects noise, which
      has potential to be used in constructing prosthetic hearing devices.

PMID- 18607754
TI  - From gene to aggressive behavior: the role of brain serotonin.
AB  - This article addresses a question at the juncture of neurophysiology and
      neurogenetics--the role of the brain neurotransmitter serotonin in the genetic
      control of behavior. Published data are presented, along with results obtained
      from studies performed at the Behavioral Neurogenomics Laboratory. The role of
      protein elements of the brain serotonin system (key enzymes in serotonin
      metabolism and serotonin 5-HT(1A) receptors), which are subject to the direct
      influence of genes, in the genetic predisposition to aggressive behavior is
      discussed. Experimental results obtained in Norwegian rats selected over more
      than 50 generations for the absence of aggressivity and for high aggressivity to
      humans are presented, along with data from experiments on mouse lines and mice
      with genetic knockout of MAO A. These data provide evidence that 1) brain
      serotonin makes a significant contribution to the mechanisms underlying
      genetically determined individual differences in aggressivity, and 2) the genes
      encoding the main enzymes of serotonin metabolism in the brain (tryptophan
      hydroxylase-1 and MAO A) and the 5-HT(1A) receptor are members of a set of genes
      modulating aggressive behavior.

PMID- 18607755
TI  - Cellular mechanisms of behavioral plasticity in simple nervous systems.
AB  - Review of our own experimental studies of the cellular mechanisms of learning in
      the nervous systems of gastropod mollusks, along with published results, allows
      identification of a number of the principles of operation of nervous systems,
      which are important for descriptions of learning and memory processes: 1) the
      main plastic changes on learning occur at the level of interneurons; 2) learning
      results in selective alteration of the efficiency of particular synaptic inputs
      of command neurons; 3) reinforcement is not linked with neuron activity in the
      receptor-sensory neuron-interneuron-motoneuron-effector reflex arc, but is
      mediated by neurons which modulate this circuit, this involving a single neuron
      in some simple cases; 4) modulator neuron activity is required for the
      acquisition of plastic modifications to defensive behavior (including associative
      modifications) but is not necessary for the reproduction of acquired responses to
      a conditioned stimulus. At the same time, modulator neurons (comprising the
      reinforcement neuron system) are required for reproduction of contextual
      associative responses; and 5) changes resulting from learning occur at at least
      two independent loci in the nervous system.

PMID- 18607756
TI  - The protective action of tumor necrosis factor alpha (TNF-alpha) on the
      hypersensitivity of pyramidal neurons in field CA1 in rat hippocampal slices
      induced by episodes of hypoxia.

PMID- 18607757
TI  - Changes in anxiety in abstinence correlate with the state of the nigrostriatal
      system in the rat hippocampus.
AB  - Opiate dependence results from impairments of neuronal plasticity, i.e., so
      called aberrant neuroplasticity, formation of which involves long-term structural
      functional rearrangements persisting even during drug abstinence. Nitric oxide
      (NO) is involved both in mediating the effects of opiates and in the mechanisms
      of some types of neuroplasticity, so NO may potentially take part in the
      development of psychopathological processes on opiate withdrawal. The present
      study addressed measures of the nitrergic system (nitric oxide synthase (NOS)
      activity and nitrite and nitrate (NO (x) (-) ) concentrations) in areas of the
      rat brain; anxiety was also assessed, in terms of behavioral measures in the
      elevated plus maze, during morphine withdrawal. NOS activity was found to
      increase by day 3, while the NO (x) (-) concentration was increased by day 6 of
      withdrawal, these changes being seen only in the hippocampus. At six days after
      morphine withdrawal, rats showed more entries into the open arms of the elevated
      plus maze and remained in these arms longer. Correlations were found between
      measures of the NO system in the hippocampus and the behavior of the animals in
      the maze. These results suggest that changes in the activity of the nitrergic
      system in the hippocampus represent one of the molecular mechanisms impairing the
      behavior of animals in abstinence.

PMID- 18607758
TI  - Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory
      in APP transgenic mice.
AB  - Anti-Abeta antibody administration to amyloid-depositing transgenic mice can
      reverse amyloid pathology and restore memory function. However, in old mice,
      these treatments also increase vascular leakage and promote formation of vascular
      amyloid deposits. Deglycosylated antibodies with reduced affinity for Fcgamma
      receptors and complement are associated with reduced vascular amyloid and
      microhemorrhage while retaining amyloid-clearing and memory-enhancing properties
      of native intact antibodies. In the current experiment, we investigated the
      effect of 3, 10, or 30 mg/kg of deglycosylated antibody (D-2H6) on amyloid
      pathology and cognitive behavior in old Tg2576 mice. We found that low doses of
      deglycosylated antibody appear more efficacious than higher doses in reducing
      pathology and memory loss in amyloid precursor protein (APP) transgenic mice.
      These data suggest that excess antibody unbound to antigen can interfere with
      antibody-mediated Abeta clearance, possibly by saturating the FcRn antibody
      transporter.

PMID- 18607759
TI  - Influence of the lipophilic external phase composition on the preparation and
      characterization of xylan microcapsules--a technical note.

PMID- 18607760
TI  - Development, validation, and clinical implementation of an assay to measure total
      antibody response to naglazyme (galsulfase).
AB  - Naglazyme (galsulfase, rhASB) was developed as enzyme replacement therapy for
      mucopolysaccharidosis type VI. Naglazyme generated an IgG antibody response in
      most patients. To better characterize Naglazyme immunogenicity, a solution phase
      bridged immunoassay was developed to measure total antibody response regardless
      of isotype. Overnight incubation of serum dilutions with rhASB labeled with
      biotin and ruthenium-based tags allowed antibody-antigen complexes to form prior
      to capture on a streptavidin plate. Neat serum was tolerated in the assay, with a
      1:10 screening dilution implemented for testing. At this dilution, the assay was
      sensitive to 75 ng/ml anti-rhASB. Titers were reported as the highest dilution
      factor with signal above a 95% confidence interval from naive individual sera.
      Precise measurement of titers, within two consecutive dilution factors, was
      observed across analysts and days. Clinical samples showed similar
      positive/negative results between the IgG ELISA and the total antibody ECLA,
      although with an imperfect correlation. Improvements in assay performance and
      implementation strategy altered some positive clinical samples to negative and
      vice versa. Comparison of the titer readout for clinical samples with the
      screening signal illustrates a range of relationships for signal versus sample
      dilution factor, confirming that signal from a screening dilution cannot directly
      predict the reported titer.

PMID- 18607761
TI  - Different origins of ZZ/ZW sex chromosomes in closely related medaka fishes,
      Oryzias javanicus and O. hubbsi.
AB  - Although the sex-determining gene DMY has been identified on the Y chromosome in
      the medaka, Oryzias latipes, this gene is absent in most Oryzias species. Recent
      comparative studies have demonstrated that, in the javanicus species group,
      Oryzias dancena and Oryzias minutillus have an XX/XY sex determination system,
      while Oryzias hubbsi has a ZZ/ZW system. Furthermore, sex chromosomes were not
      homologous in these species. Here, we investigated the sex determination
      mechanism in Oryzias javanicus, another species in the javanicus group. Linkage
      analysis of isolated sex-linked DNA markers showed that this species has a ZZ/ZW
      sex determination system. The sex-linkage map showed a conserved synteny to the
      linkage group 16 of O. latipes, suggesting that the sex chromosomes in O.
      javanicus are not homologous to those in any other Oryzias species. Fluorescence
      in-situ hybridization analysis confirmed that the ZW sex chromosomes of O.
      javanicus and O. hubbsi are not homologous, and showed that O. javanicus has the
      morphologically heteromorphic sex chromosomes, in which the W chromosome has 4,6
      diamino-2-phenylindole-positive heterochromatin at the centromere. These findings
      suggest the repeated evolution of new sex chromosomes from autosomes in Oryzias,
      probably through the emergence of new sex-determining genes.

PMID- 18607762
TI  - Online detection of waterborne bioavailable copper by valve daily rhythms in
      freshwater clam Corbicula fluminea.
AB  - Freshwater clam Corbicula fluminea, a surrogate species in metal toxicity
      testing, is a promising bioindicator of impairment in aquatic ecosystems. Little
      is known, however, about the relationship between clam valve daily rhythmic
      response and metal bioavailability related to a metal biological early warning
      system (BEWS) design. The purpose of this study was to link biotic ligand model
      (BLM)-based bioavailability and valve daily rhythm in C. fluminea to design a
      biomonitoring system for online in situ detection of waterborne copper (Cu). We
      integrated the Hill-based dose-time-response function and the fitted daily rhythm
      function of valve closure into a constructed programmatic mechanism. The
      functional presentation of the present dynamic system was completely demonstrated
      by employing a LabVIEW graphic control program in a personal computer. We used
      site-specific effect concentration causing 10% of total valve closure response
      (EC10) as the detection threshold to implement the proposed C. fluminea-based Cu
      BEWS. Here our results show that the proposed C. fluminea-based BEWS could be
      deliberately synthesized to online in situ transmit rapidly the information on
      waterborne bioavailable Cu levels under various aquatic environmental conditions
      through monitoring the valve daily rhythmic changes. We suggested that the
      developed C. fluminea-based dynamic biomonitoring system could assist in
      developing technically defensible site-specific water quality criteria to promote
      more efficient uses in water resources for protection of species health in
      aquatic environments.

PMID- 18607763
TI  - Diurnal and intra-urban particle concentrations in relation to windspeed and
      stability during the dry season in three African cities.
AB  - The spatial and temporal variations of PM(2.5), PM(10) and TSP in three African
      cities of different sizes (Dar es Salaam, Ouagadougou and Gaborone) were
      investigated using portable particle counters. Three different areas (downtown,
      green residential and traditional residential) and a reference site were
      designated in each of the cities in order to detect intra-urban and temporal
      variability. Morning, noon and night measurements were conducted in the urban
      areas while observations at reference stations were made continuously over the
      field periods. A clear diurnal pattern in particle concentrations was found in
      inland Gaborone and Ouagadougou, with morning and night peaks where the latter
      was the highest. However, in coastal Dar es Salaam the night peak was almost
      absent due to delayed stabilisation of the air. Particle concentrations at the
      Ouagadougou reference station were extreme. The direct contribution of vehicle
      emissions are of secondary importance since the PM(2.5)/PM(10) ratios are low
      (0.1-0.3). Much of the particles are supposed to be soil particles that are
      entrained in the air by daytime high windspeeds followed by nighttime subsidence
      as the air is stabilised and windspeed decreases. However, in all three cities,
      resuspension are important as areas with a network of unpaved roads showed the
      highest concentrations of suspended particles. Generally, the central business
      district had the lowest concentrations of particulate matter.

PMID- 18607764
TI  - Geo-spatial analysis of land-water resource degradation in two economically
      contrasting agricultural regions adjoining national capital territory (Delhi).
AB  - The present study was aimed at characterizing the soil-water resource degradation
      in the rural areas of Gurgaon and Mewat districts, the two economically
      contrasting areas in policy zones-II and III of the National Capital Region
      (NCR), and assessing the impact of the study area's local conditions on the type
      and extent of resource degradation. This involved generation of detailed spatial
      information on the land use, cropping pattern, farming practices, soils and
      surface/ground waters of Gurgaon and Mewat districts through actual resource
      surveys, standard laboratory methods and GIS/remote sensing techniques. The study
      showed that in contrast to just 2.54% (in rabi season) to 4.87% (in kharif
      season) of agricultural lands in Gurgaon district, about 11.77% (in rabi season)
      to 24.23% (in kharif season) of agricultural lands in Mewat district were
      irrigated with saline to marginally saline canal water. Further, about 10.69% of
      agricultural lands in the Gurgaon district and 42.15% of agricultural lands in
      the Mewat district were drain water irrigated. A large part of this surface water
      irrigated area, particularly in Nuh (48.7%), Nagina (33.5%), and Punhana (24.1%)
      blocks of Mewat district, was either waterlogged (7.4% area with <or=2 m ground
      water depth) or at risk of being waterlogged (17.1% area with 2-3 m ground water
      depth). Local resource inventory showed prevalence of several illegal private
      channels in Mewat district. These private channels divert degraded canal waters
      into the nearby intersecting drains and thereby increase extent of surface
      irrigated agricultural lands in the Mewat district. Geo-spatial analysis showed
      that due to seepage of these degraded waters from unlined drains and canals,
      ground waters of about 39.6% of Mewat district were salt affected (EC(m)ean =
      7.05 dS/m and SAR(m)ean = 7.71). Besides, sub-surface drinking waters of almost
      the entire Mewat district were contaminated with undesirable concentrations of
      chromium (Cr 2.0-3.23 ppm), manganese (Mn: 0.80-1.55 ppm), nickel (Ni: 0.02-0.10
      ppm) and lead (Pb: 0.40-0.83 ppm). Ground waters (42.5%) of Farukh Nagar
      irrigated with Najafgarh drain water and adjoining (industrialized) Gurgaon and
      Pataudi blocks were also salt affected and laden with undesirable Cr
      concentrations (>0.05 ppm). In fact, sub-surface drinking waters of some areas
      around battery and automobile manufacturing units in Gurgaon and Pataudi blocks
      were associated with exceptionally high (>0.1 ppm) Ni concentrations. In general,
      the ground waters of waterlogged or potentially waterlogged areas in the rural
      areas of Mewat were more contaminated than the ground waters in the rural areas
      of Gurgaon district with deeper (>5 m) water depths.Though Cr concentrations in
      the surface and sub-surface irrigation waters of both Gurgaon and Mewat districts
      were far above the maximum permissible limit of 1 ppm, their bio-available soil
      Cr concentrations were well within permissible limit. Even bio-available Ni
      concentrations in agricultural lands of Gurgaon district associated with Ni
      contaminated sub-surface irrigations were well within desirable limit of 0.20
      ppm. This was primarily attributed to the calcareous nature of the soils of the
      study area. About 35% of Gurgaon district and 59% of Mewat district irrigated
      with poor quality waters were salt-affected. These waterlogged/potentially
      waterlogged calcareous-salt affected soils of Mewat district were having acute
      zinc (Zn) deficiency (<0.6 ppm). Some areas with extremely high iron (Fe: 20-25
      ppm) and Mn (10-25 ppm) concentrations were also noticed in the Gurgaon, Nuh and
      Punhana blocks. Generation of reduced conditions owing to paddy cultivation in
      areas with 3-3.5 m water depths appeared to be the main cause of such point
      contaminations. Extensive cadmium (Cd) contamination was also noticed in the
      waterlogged sodic agricultural lands of Nagina village in Mewat district
      associated with a large scale scrap automobile and battery business. The study
      could document the processes and provide spatially accurate information to the
      managers (e.g., National Capital Region Planning Board) and the concerned citizen
      groups. It could, in fact, clearly point out that dumping of industrial and
      domestic wastewaters especially from NCT-Delhi into river Yamuna and, to some
      extent, from NCT-Delhi re-located hazardous industrial units into Najafgarh drain
      tributaries at Delhi-Gurgaon boundary, and poor "off-farm" water management
      practices were the main reasons for extensive (point/non-point source) land-water
      degradation in Gurgaon and Mewat districts of NCR.

PMID- 18607765
TI  - Effect of dietary alternative lipid sources on haematological parameters and
      serum constituents of Heterobranchus longifilis fingerlings.
AB  - The worldwide increase in aquaculture production and the decrease of wild fish
      stocks has made the replacement of fish oil (FO) in aquafeed industry a priority.
      Therefore, the use of terrestrial animal fats and vegetable oils, which has lower
      cost and larger supplies, may be good as substitute for FO. This study
      investigate the effects of total replacement of FO by two terrestrial animal fats
      (pork lard and poultry fat) and three vegetable oils (palm kernel oil, sheabutter
      oil and sunflower oil) on haematological and serum biochemical profile of
      Heterobranchus longifilis over 70 days. FO-diet was used as the control. The
      haematological parameters were significantly affected by dietary lipid sources.
      Serum total protein was not influenced by the dietary lipids. However, serum
      cholesterol was significantly higher in fish fed diet containing sunflower oil.
      Glucose and activities of liver enzymes in blood serum were significantly reduced
      in fish fed alternative lipids when compared with the control. These results
      indicate that FO can be replaced completely with alternative lipids without any
      serious negative health impacts.

PMID- 18607766
TI  - Methionine+cystine requirement of broiler chickens fed low-density diets under
      tropical conditions.
AB  - Two experiments were conducted to determine the M+C requirement of straight-run
      broiler chickens (Hubbard x Hubbard) during the period 4-21 (Exp. 1) and 21-40
      (Exp. 2) days of age. Experiments were conducted during summer months (July
      August) in open-sided houses, thus exposing chicks to chronic heat stress. Daily
      min-max temperature averaged 26-37C (Exp. 1) and 23-36C (Exp. 2). M+C deficient
      basal diets were formulated to contain low-nutrient-density, i.e., 2750 kcal per
      kg ME, 20.1% CP (Exp. 1), and 2780 kcal per kg ME, 17.0% CP (Exp. 2). Diets were
      supplemented with DL-methionine to provide total M+C level ranging from 0.64 to
      0.89 % (six increments) and 0.54 to 0.79% (six increments), respectively in
      experiment 1 and 2. Requirements (0.95 of the maximum quadratic response) were
      found to be 0.77 and 0.75% total M+C, respectively for gain and feed efficiency,
      during 4-21 days; and 0.67% total M+C for both gain and feed efficiency during 21
      40 days of age. Calculated on the digestible M+C basis, the estimates were 0.67
      and 0.65% respectively for gain and feed efficiency during 4-21 days of age; and
      0.60% for gain and feed efficiency during 21-40 days of age.

PMID- 18607767
TI  - Bovine tuberculosis of cattle in three districts of northwestern Ethiopia.
AB  - The prevalence of bovine tuberculosis (BTB) infection in cattle was investigated
      in extensive and intensive production systems in three districts of northwestern
      Ethiopia. Single comparative intradermal tuberculin test (SCIDTT) was used in the
      study. The prevalence of BTB infection as determined by SCIDTT was 9.7% whereas
      the non-specific infection prevalence was 10.8%. In the extensive system the
      prevalence was 8.2% and 11.3%; under intensive system the prevalence was 22.1%
      and 6.3% for BTB and non-specific infections respectively. The prevalence of BTB
      was significantly higher in the intensive than extensive production systems. Of
      the 75 herds tested 41 (54.7%) had BTB infections, 68.9% of the BTB positive
      herds were in the extensive system and 40% of herds in the intensive systems
      (small dairy farms) had BTB infections.

PMID- 18607768
TI  - Molecular diagnosis of German patients with late-onset glycogen storage disease
      type II.
AB  - In patients with late-onset glycogen storage disease type II, one mutation, c.-32
      13T>G, in the alpha-glucosidase (GAA) gene is identified frequently in European
      populations from different regions along with many rarer mutations. We have
      performed molecular genetic investigations in 18 German index patients with late
      onset disease. The c.-32-13T>G, c.525delT (p.Glu176fsX45), and
      c.2481+102_2646+31del mutations were detected by PCR/restriction enzyme digest.
      Other mutations were detected by sequencing. All patients were compound
      heterozygous and 17 patients harboured the c.-32-13T>G mutation. Seven other
      previously described mutations (including the c.-32-13T>G) were identified, of
      which the p.C103G (c.307T>G) and the c.2481+102_2646+31del mutations were present
      each in three unrelated patients. Sequencing revealed five novel mutations.
      CONCLUSIONS: Genetic testing was able to identify the genetic defects in all
      patients and screening of the c.-32-13T>G mutation identified 94% of the cases.
      This is important for quick and reliable diagnosis, especially in view of enzyme
      replacement. Among the rarer mutations, c.2481+102_2646+31del and p.C103G are
      rather frequent in Germany.

PMID- 18607769
TI  - Molecular cloning and characterization of the Dicer-like 2 gene from Brassica
      rapa.
AB  - Dicer-like proteins (DCLs) are involved in small RNA-mediated development and
      viral defense in plants. In model plants, at least four DCLs have been found and
      a number of studies have helped to understand their function. However, the
      function of the Dicer or DCLs in other plants is still unclear. Here, we report
      the full-length cDNA sequence of Brassica rapa ssp. chinensis DCL2 (BrDCL2) gene,
      which contains a 4,179 bp open reading frame (ORF) encoding a protein of 1,392
      amino acids. At the 3' end of BrDCL2, clones with three different lengths of 3'
      untranslated region were found. An alternative splice variant of BrDCL2,
      BrDCL2sv, in which one intron was retained between exon9 and exon10, was also
      cloned. Because of a change in the coding sequence resulting in a premature
      terminal codon, BrDCL2sv was expected to translate a short peptide containing the
      whole DEXHc domain.

PMID- 18607770
TI  - In vitro interaction between the N-terminus of the Ewing's sarcoma protein and
      the subunit of RNA polymerase II hsRPB7.
AB  - In vivo and in vitro expressed N-terminal sequence of EWS (EAD) and hsRPB7
      (subunit of human RNA polymerase II) were probed for protein-protein interactions
      using pull-down assays. In result, it was found that the proteins 57Z (residues 1
      57 of EAD) and hsRPB7 interact in vitro forming a stable complex. The direct
      interaction between 57z and hsRPB7 indicate that DHR-related peptides and other
      small molecules, targeted to N-terminus of EWS might possess therapeutic
      potentialities as anti-cancer agents to function as inhibitors of EAD-mediated
      transactivation.

PMID- 18607771
TI  - Potent induction of total cellular and mitochondrial antioxidants and phase 2
      enzymes by cruciferous sulforaphane in rat aortic smooth muscle cells:
      cytoprotection against oxidative and electrophilic stress.
AB  - Sulforaphane, a cruciferous isothiocyanate compound, upregulates cytoprotective
      genes in liver, but its effects on antioxidants and phase 2 defenses in vascular
      cells are unknown. Here we report that incubation of rat aortic smooth muscle A10
      cells with sulforaphane (0.25-5 microM) resulted in concentration-dependent
      induction of a spectrum of important cellular antioxidants and phase 2 enzymes,
      including superoxide dismutase (SOD), catalase, the reduced form of glutathione
      (GSH), glutathione peroxidase, glutathione reductase (GR), glutathione S
      transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1). Sulforaphane also
      increased levels/activities of SOD, catalase, GSH and GST in isolated
      mitochondria of aortic smooth muscle cells. Time-dependent sulforaphane-induced
      increases in the mRNA levels for MnSOD, catalase, the catalytic subunit of gamma
      glutamylcysteine ligase, GR, GST-A1, GST-P1, and NQO1 were observed. Pretreatment
      with sulforaphane (0.5, 1, and 5 microM) protected aortic smooth muscle cells
      from oxidative and electrophilic cytotoxicity induced by xanthine oxidase
      (XO)/xanthine, H2O2, SIN-1-derived peroxynitrite, 4-hydroxy-2-nonenal, and
      acrolein. Furthermore, sulforaphane pretreatment prevented intracellular
      accumulation of reactive oxygen species (ROS) after exposure of the cells to
      XO/xanthine, H2O2, or SIN-1. Taken together, this study demonstrates that in the
      aortic smooth muscle cells sulforaphane at physiologically relevant
      concentrations potently induces a series of total cellular as well as
      mitochondrial antioxidants and phase 2 enzymes, which is accompanied by
      dramatically increased resistance of these vascular cells to oxidative and
      electrophilic stress.

PMID- 18607772
TI  - Selection of reference genes for quantitative real-time RT-PCR studies in mouse
      brain.
AB  - Since a growing number of studies based on the real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) continue to be published in order to highlight
      genes specifically involved in brain development, maturation, and function, the
      identification of reference genes suitable for this kind of experiments is now an
      urgent need in the neuroscience field. The aim of this work was to verify the
      suitability of some very common housekeeping genes (such as Gapdh, 18s, and B2m)
      and of some relatively new control genes (such as Pgk1, Tfrc, and Gusb) during
      mouse brain maturation. We tested the candidate reference genes in mouse whole
      brain, cerebellum, brain stem, hippocampus, medial septum, frontal neocortex, and
      olfactory bulb. Moreover, we reported the first complete study of Pgk1 expression
      throughout the development and the aging of mouse brain. Although no tested gene
      showed to be the optimal reference for all mouse brain regions, in general, the
      new housekeeping genes were highly stable in most of the analyzed regions. Above
      all, with few exceptions, Pgk1 showed to be a reliable control for the analyzed
      mouse brain regions during development, maturation, and aging.

PMID- 18607773
TI  - The genetics of Alzheimer's disease in Brazil: 10 years of analysis in a unique
      population.
AB  - Alzheimer's Disease (AD) is the most common type of dementia among the elderly,
      with devastating consequences for the patient, their relatives, and caregivers.
      More than 300 genetic polymorphisms have been involved with AD, demonstrating
      that this condition is polygenic and with a complex pattern of inheritance. This
      paper aims to report and compare the results of AD genetics studies in case
      control and familial analysis performed in Brazil since our first publication, 10
      years ago. They include the following genes/markers: Apolipoprotein E (APOE), 5
      hidroxytryptamine transporter length polymorphic region (5-HTTLPR), brain-derived
      neurotrophin factor (BDNF), monoamine oxidase A (MAO-A), and two simple-sequence
      tandem repeat polymorphisms (DXS1047 and D10S1423). Previously unpublished data
      of the interleukin-1alpha (IL-1alpha) and interleukin-1 beta (IL-1beta) genes are
      reported here briefly. Results from others Brazilian studies with AD patients are
      also reported at this short review. Four local families studied with various
      markers at the chromosome 21, 19, 14, and 1 are briefly reported for the first
      time. The importance of studying DNA samples from Brazil is highlighted because
      of the uniqueness of its population, which presents both intense ethnical
      miscegenation, mainly at the east coast, but also clusters with high inbreeding
      rates in rural areas at the countryside. We discuss the current stage of
      extending these studies using high-throughput methods of large-scale genotyping,
      such as single nucleotide polymorphism microarrays, associated with
      bioinformatics tools that allow the analysis of such extensive number of genetics
      variables, with different levels of penetrance. There is still a long way between
      the huge amount of data gathered so far and the actual application toward the
      full understanding of AD, but the final goal is to develop precise tools for
      diagnosis and prognosis, creating new strategies for better treatments based on
      genetic profile.

PMID- 18607774
TI  - Identification of novel RasGRF1 interacting partners by large-scale proteomic
      analysis.
AB  - The brain-specific Ras guanine nucleotide exchange factor RasGRF1 is a protein
      harbouring a complex array of structural motifs. It contains a pleckstrin
      homology (PH1) domain, a coiled coil region (CC) and an ilimaquinone (IQ) one in
      addition to the catalytic Ras and Rac exchange factor domains. In this study, we
      used the recombinant N-terminal PH1, CC and IQ region (PHCCIQ) fused to the
      chitin-binding domain to isolate interacting proteins from mouse brain extracts.
      The use of an advanced software tool, the Pep-Miner, allowed clustering similar
      spectra from multiple mass spectrometry analysis, simplifying and improving the
      analysis of the complex peptide mixture. The most representative classes of
      RasGRF1-interacting proteins were ribosomal and other RNA-binding proteins,
      cytoskeletal proteins and proteins involved in vesicular trafficking. We
      confirmed the interaction of some of the identified proteins using different
      experimental approaches. We also demonstrated an RNA-dependent association of the
      PHCCIQ moiety of RasGRF1 with ribosomal protein S6 and Ras-GTPase-activating
      protein SH3-domain binding protein 2. In addition, we found that purified total
      RNA binds to the PHCCIQ fusion protein and the recombinant protein associates
      with poly(A)-sepharose. These data indicate that RasGRF1 can interact with
      different protein categories and exhibits a potential RNA-binding property.

PMID- 18607775
TI  - In memory of our teacher, Dr. Akira Arimura.

PMID- 18607777
TI  - Changes in the expression of PACAP-like compounds during the embryonic
      development of the earthworm Eisenia fetida.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed at very
      early stages in the vertebrate nervous system, and its functions in the embryonic
      development have been shown by various studies. PACAP is an extremely conserved
      molecule in phylogeny; however, little is known about its presence and functions
      in invertebrates. Our previous studies have shown the occurrence of PACAP-like
      immunoreactivity in the invertebrate nervous system. The aim of this study was to
      investigate the presence and localization of PACAP-like compounds during the
      embryonic development of earthworms from cocoon deposition to hatching using
      immunological methods (radioimmunoassay, dot blot, immunohistochemistry). PACAP
      like immunoreactive compounds were detected at very early stages of the embryonic
      development of the earthworm Eisenia fetida. No significant changes were observed
      during the early stages in the developing embryo, but a marked increase occurred
      before hatching. In contrast, during the embryonic development, the level of
      PACAP-like compounds gradually decreased in cocoon fluids. Immunohistochemistry
      revealed the presence of PACAP-like immunoreactive cell bodies and processes in
      the developing body wall, prostomium, pharyngeal wall, and central nervous
      system. Cells located in the body wall correspond to putative progenitor cells of
      primary sensory cells. In the present study, we also showed that the clitellum
      (reproductive organ) of sexually mature worms contained significantly higher
      levels of PACAP-like immunoreactivity than other regions of the same animals or
      the clitellar region of a non-reproducing animal. In summary, these observations
      provide a morphological basis and suggest a role of PACAP(-like peptides) in the
      reproductive and developmental functions of invertebrates.

PMID- 18607776
TI  - VIP, from gene to behavior and back: summarizing my 25 years of research.
AB  - Vasoactive intestinal peptide (VIP) is an interesting example of a 28-amino acid
      neuropeptide that is abundantly expressed in discrete brain regions/neurons and
      hence may contribute to brain function. This short review summarizes my own point
      of view and encompasses 25 years of work and over 100 publications targeting the
      understanding of VIP production and biological activity. The review starts with
      our original cloning of the VIP gene, it then continues to discoveries of
      regulation of VIP synthesis and the establishment of the first VIP transgenic
      mice. The review ends with the identification of novel VIP analogs that helped
      decipher VIP's important role during development, in regulation of the biological
      clock(s) and diurnal rhythms, sexual activity, learning and memory as well as
      social behavior, and cancer. This review cites only articles that I have
      coauthored and gives my own perspective of this exciting ever-growing field.

PMID- 18607778
TI  - Biogenesis and transport of secretory granules to release site in neuroendocrine
      cells.
AB  - Biogenesis and post-Golgi transport of peptidergic secretory granules to the
      release site are crucial for secretion of neuropeptides from neuroendocrine
      cells. Recent studies have uncovered multilevel molecular mechanisms for the
      regulation of secretory granule biogenesis. Insulinoma-associated protein 2
      (ICA512/IA-2), polypyrimidine-tract binding protein, and chromogranin A have been
      identified to regulate secretory granule biogenesis at the transcriptional,
      posttranscriptional, and posttranslational levels, respectively, by increasing
      granule protein levels, which in turn drives granule formation after stimulation.
      Post-Golgi transport of secretory granules is microtubule-based and mediated by
      transmembrane carboxypeptidase E (CPE). The cytoplasmic tail of CPE anchors
      secretory granules to the microtubule motors, kinesin-2 and -3, or dynein, via
      interaction with the adaptor, dynactin, to mediate anterograde and retrograde
      transport, respectively.

PMID- 18607779
TI  - Agonistic behavior of PACAP6-38 on sensory nerve terminals and cytotrophoblast
      cells.
AB  - The effects of pituitary adenylate cyclase activating polypeptide (PACAP) are
      mediated through G-protein-coupled receptors, the specific PAC1 receptor and
      VPAC1 and VPAC2 receptors which bind vasoactive intestinal peptide with similar
      affinity. Based on binding affinity studies, PACAP6-38 was discovered as a potent
      antagonist of PAC1 and it has been used by hundreds of studies as a PACAP
      antagonist. Recently, we have found that in certain cells/tissues, PACAP6-38 does
      not antagonize PACAP-induced effects, but surprisingly, it exerts similar actions
      to PACAP1-38, behaving as an agonist. In the present study, we report on the
      agonistic behavior of PACAP6-38 on neuropeptide release from sensory nerves of
      the isolated rat trachea and on the MAPK signaling pathways in cytotrophoblast
      cells. In isolated rat tracheae, PACAP6-38, similarly to PACAP1-38, induced
      significant inhibitory effects on the release of three simultaneously measured
      sensory neuropeptides, substance P, calcitonin gene-related peptide, and
      somatostatin evoked by both chemical excitation and electrical field stimulation
      of capsaicin-sensitive afferents. Effects of PACAP6-38 were the same as those of
      PACAP1-38 on MAPK signaling in human cytotrophoblast cells. Western blot analysis
      showed that both peptide forms stimulated ERK1/2 and JNK phosphorylation, while
      they both inhibited p38 MAPK phosphorylation. The most pronounced effects were
      observed when both peptides were present. In summary, our results show that
      PACAP6-38, which is a PACAP receptor antagonist in most cells/tissues, can behave
      as an agonist in other systems. The increasing interest in the effects of PACAP
      requires further studies on the pharmacological properties of the peptide and its
      analogues.

PMID- 18607780
TI  - Describing different brain computer interface systems through a unique model: a
      UML implementation.
AB  - All the protocols currently implemented in brain computer interface (BCI)
      experiments are characterized by different structural and temporal entities.
      Moreover, due to the lack of a unique descriptive model for BCI systems, there is
      not a standard way to define the structure and the timing of a BCI experimental
      session among different research groups and there is also great discordance on
      the meaning of the most common terms dealing with BCI, such as trial, run and
      session. The aim of this paper is to provide a unified modeling language (UML)
      implementation of BCI systems through a unique dynamic model which is able to
      describe the main protocols defined in the literature (P300, mu-rhythms, SCP,
      SSVEP, fMRI) and demonstrates to be reasonable and adjustable according to
      different requirements. This model includes a set of definitions of the typical
      entities encountered in a BCI, diagrams which explain the structural correlations
      among them and a detailed description of the timing of a trial. This last
      represents an innovation with respect to the models already proposed in the
      literature. The UML documentation and the possibility of adapting this model to
      the different BCI systems built to date, make it a basis for the implementation
      of new systems and a mean for the unification and dissemination of resources. The
      model with all the diagrams and definitions reported in the paper are the core of
      the body language framework, a free set of routines and tools for the
      implementation, optimization and delivery of cross-platform BCI systems.

PMID- 18607781
TI  - High frequency plasmid recombination mediated by 28 bp direct repeats.
AB  - The stability in Escherichia coli of a mammalian expression vector (pCIneo) and
      its derivative candidate DNA vaccine (pGPV-PV) is described. These multicopy pMB1
      type plasmids were found to recombine in several recA E. coli strains due to the
      presence of two 28 bp direct repeats flanking intervening sequences of 1.6 kb
      (pCIneo) and 3.2 kb (pGPV-PV). In this recombination event, one of the direct
      repeats and the intervening sequence were deleted or duplicated, originating
      monomeric or/and hetero-dimeric plasmid forms, respectively. Additionally, the
      plasmid rearrangement led to the acquisition of a kanamycin resistance phenotype.
      Recombination frequencies between 7.8 x 10(-7) and 3.1 x 10(-5) were determined
      for DH5alpha and JM109(DE3) strains, respectively. Higher recombination
      frequencies were found in cells previously grown up to stationary growth phase
      being the monomeric plasmid form the prevalent one. Real-time PCR quantification
      revealed the presence of approximately 1.5 x 10(4) recombined molecules per 2 x
      10(5 )cells pre-kanamycin exposure. Under selective pressure of this antibiotic,
      the number of recombined molecules increased approximately 2,000-fold in a 48-h
      period replacing the original plasmid form. The high frequency, at which deletion
      duplication occurred in the absence of kanamycin selective pressure, should be
      regarded as a safety concern. This work highlights the impact of mutational hot
      spots on expression and cloning plasmid vectors and the need to carefully design
      plasmid vectors.

PMID- 18607782
TI  - Endothelial and hematopoietic progenitor cells (EPCs and HPCs): hand in hand fate
      determining partners for cancer cells.
AB  - Tumor growth and metastasis need new vessel formation by angiogenesis provided by
      mature endothelial cells and postnatal vasculogenesis provided by endothelial
      progenitor cells (EPCs). Emerging data suggest a coordinated interaction between
      EPCs and hematopoietic progenitor cells (HPCs) in these processes. The complexity
      of the mechanisms governing the new vessel formation by postnatal vasculogenesis
      has increased by new evidence that not only bone marrow derived EPCs and HPCs
      seem to be involved in this process but also local progenitors residing within
      the vascular wall are mobilized and activated to new vessel formation by tumor
      cells. This review attempts to bring these systemic and local players of
      postnatal vasculogenesis together and to highlight their role in tumor growth and
      mestastasis.

PMID- 18607784
TI  - Prolonged response to gefitinib in bone metastasis.

PMID- 18607783
TI  - The therapeutic potential of embryonic and adult stem cells for skeletal muscle
      regeneration.
AB  - Muscular dystrophy (MD) refers to a group of more than 30 genetically and
      clinically heterogeneous disorders, characterized by progressive weakness and
      degeneration of the skeletal muscles that control movement. To date, MD is still
      incurable but increasing evidence suggests that stem cells might represent a
      therapeutic option in the future. This review will outline recent progress in
      this field involving the use of adult and embryonic stem cells. We will discuss
      in further detail the nature of these cells and their distinct biological
      properties which lead to their unique advantages and disadvantages in regard to
      therapeutic application.

PMID- 18607785
TI  - Porcine lung surfactant protein B gene (SFTPB): cDNA sequencing, chromosomal
      location, and expression studies.
AB  - The porcine surfactant protein B (SFTPB) is a single copy gene on chromosome 3.
      Three different cDNAs for the SFTPB have been isolated and sequenced. Nucleotide
      sequence comparison revealed six nonsynonymous single nucleotide polymorphisms
      (SNPs), four synonymous SNPs and an in-frame deletion of 69 bp in the region
      coding for the active protein. Northern analysis showed lung-specific expression
      of three different isoforms of the SFTPB transcript. The expression level for the
      SFTPB gene is low in 50 days-old fetus and it increases during lung development.
      Quantitative real-time polymerase chain reaction (qPCR) showed significant down
      regulation of the SFTPB in pigs with Actinobacillus pleuropneumoniae lung
      infection.

PMID- 18607786
TI  - Characterization of porcine ASB6 gene and transcripts-comparison of mammalian
      transcripts.
AB  - A member of the porcine Ankyrin repeat and suppressor of cytokine signaling
      (SOCS) Box protein family (ASB), designed as ASB6, was sequenced and the genomic
      organization of the six exons was determined. We present here a detailed analysis
      of ASB6 transcripts in pigs. We demonstrate the existence of an alternative
      transcript resulting from intron retention. This secondary transcript, if
      functional, encodes a protein without SOCS box. A comparison of mammalian ASB6
      transcripts is performed to demonstrate the importance of transcripts encoding
      for a truncated ASB6 protein.

PMID- 18607787
TI  - Sequence identification, tissue distribution and polymorphism of the porcine
      cathepsin D (CTSD) gene.
AB  - Cathepsin D (CTSD), a major ubiquitously expressed aspartic protease, is not only
      involved in muscle protein degradation, but also related to some pathological
      processes. In this study, we characterized the full-length cDNA, genomic DNA
      sequence, expression profile and polymorphism of the porcine CTSD gene. The full
      length cDNA of porcine CTSD gene and the predicted protein sequence shared high
      identities wih other mammalian orthologous. Northern-blot analysis and Reverse
      transcription (RT)-PCR results indicated that the CTSD gene has one transcript of
      approximately 2.0 kb in normal tissues and was expressed ubiquitously in pigs,
      without significant differences in porcine heart, liver, spleen, lung, kidney,
      stomach, fat, triceps brachi, biceps femoris, and longissimus muscles. The
      porcine CTSD gene spans approximately 9.0 kb including nine exons. All
      exon/intron boundaries adhere to the GT/AG rule. Altogether 35 nucleotide
      polymorphisms of CTSD gene were discovered between Duroc, Landrace, Erhualian,
      and Dahuabai pigs. These polymorphisms included three missense mutations, eight
      synonymous mutations, and 24 intronic substitutions, and most polymorphisms are
      located in the intron 4 and 5. Three polymorphisms were genotyped in Duroc,
      Landrace, Dahuabai, and Erhualian pigs by PCR-RFLP method, and significant
      differences of their genotype frequencies were observed between Chinese native
      breeds (Dahuabai and Erhualian) and western breeds (Duroc and Landrace).

PMID- 18607788
TI  - Molecular characterization and SNP development for the porcine IL6 and IL10
      genes.
AB  - Different cytokines are secreted in response to specific microbial molecules
      referred to as pathogen associated molecular patterns (PAMPs). Interleukin 6
      (IL6) and interleukin 10 (IL10), both secreted by macrophages and lymphocytes,
      play a central role in the immunological response. In this work we obtained the
      genomic structure and complete DNA sequence of the porcine IL6 and IL10 genes and
      identified polymorphisms in the genomic sequences of these genes on a panel of
      ten different pig breeds. Comparative intra- and interbreed sequence analysis
      revealed a total of eight polymorphisms in the porcine IL6 gene and 21 in the
      porcine IL10 gene, which include single nucleotide polymorphisms (SNPs) and
      insertion deletion polymorphisms (indels). Additionally, the chromosomal
      localization of the IL10 gene was determined by FISH and RH mapping.

PMID- 18607789
TI  - Using mtDNA sequences to estimate SNP parameters in ESTs.
AB  - Discovery of single nucleotide polymorphisms (SNPs) requires analysis of
      redundant sequences such as those available in large public databases. The
      ability to detect SNPs, especially those of low frequency, is dependent on the
      depth and scale of the discovery effort. Large numbers of SNPs have been
      identified by mining large-scale EST surveys and whole genome sequencing
      projects. These surveys however are subject to ascertainment bias and the
      inherent errors in large-scale single pass sequencing efforts. For example, the
      number of steps involved in the construction and sequencing of cDNA libraries
      make ESTs highly error prone, resulting in an increased frequency of nonvalid
      SNPs obtained in these surveys. Sequences of mtDNA genes are often incorporated
      into cDNA libraries as an artifact of the library construction process and are
      typically either subtracted from cDNA libraries or are considered superfluous
      when evaluating the information content of EST datasets. Sequences of mtDNA genes
      provide a unique resource for the analysis of SNP parameters in EST projects.
      This study uses sequences from four turkey muscle cDNA libraries to demonstrate
      how mtDNA sequences gleaned from collections of ESTs can be used to estimate SNP
      parameters and thus help predict the validity of SNPs.

PMID- 18607790
TI  - Genomic organization and promoter analysis of the bovine ADAM12 gene.
AB  - A disintegrin and metalloprotease (ADAM) 12 is a member of the ADAM family
      possessing a putative role in a variety of biological processes such as
      modulation of proteolytic processing, cell adhesion, cell fusion, and signaling.
      Recently, it has been suggested that ADAM12 is involved in regulation of
      adipogenesis as well as myogenesis. In this study, we have determined the genomic
      structure of 5'- and 3'-regions in the bovine ADAM12 gene. We could obtain
      characteristics of lower homology of its exon 2 with human counterpart. Human
      exon S19 encodes for the sequence specific to a shorter secreted form of ADAM12S.
      The bovine ADAM12 gene had no canonical 3'-splice acceptor site at 5'-side of the
      putative exon S19, suggesting that the cattle could not produce a ADAM12S
      counterpart. To identify the regulatory elements, a 12 kb 5'-flanking region of
      the gene was cloned and luciferase reporter assay was carried out. Reporter
      plasmids with different length of proximal promoter region indicated the similar
      patterns of promoter activities between 3T3-L1 preadipose and Cos-1 nonadipose
      cells. However, 2.0 and 0.2 kb fragments located at - 8 and - 4.5 kb upstream of
      the putative transcription start site, respectively, increased the ADAM12
      promoter activity about 1.5- to 2-fold in 3T3-L1, but not in Cos-1. These results
      suggested that the two distal regions might contribute to the preadipocyte
      specific expression of ADAM12 gene.

PMID- 18607791
TI  - Gene expression of heart- and adipocyte-fatty acid-binding protein and
      correlation with intramuscular fat in Chinese chickens.
AB  - This study examined the association between expression of heart- and adipocyte
      fatty acid binding-protein genes (H- and A-FABP) with intramuscular fat
      percentage (IFP) in two Chinese chicken breeds (Beijingyou [BJY] and Jingxing
      [JX]). The results showed that age and breed had significant effects on the FABP
      expression. A-FABP mRNA levels were dramatically higher in BJY than in JX
      chickens and in males than in females. The results indicate that transcription of
      H- and A-FABP genes was significantly correlated with IFP in two breeds of
      chicken.

PMID- 18607792
TI  - Sequence variation of the alpha-lactalbumin gene in Holstein and Nellore cows.
AB  - The alpha-lactalbumin is a subunit of lactose-synthase, an enzyme responsible for
      lactose production, a disaccharide that influences milk production. Sequence
      variations of bovine alpha -lactalbumin have been associated with differences in
      milk yield. This study aimed to analyze allelic frequency differences at position
      - 1689 (g. A > G) and + 15 (g. A > G) of the alpha-lactalbumin gene in Holstein
      (Bos taurus) and Nellore (Bos indicus) cows. Blood samples were analyzed from 34
      Holstein, 104 Nellore, and 99 Dairy Nellore cows using PCR-RFLP. The different
      RFLP patterns were sequenced and a novel sequence variation on nucleotide - 46
      was identified. An adenine at this position was designated as the A allele and a
      guanine was designated B allele. The frequencies of alleles A - 1689, A - 46, and
      A + 15 differed between Holstein and both Nellore breeds. The results show that
      differences in alpha-lactalbumin allelic variants in the 5'-flanking and the 5'
      UTR region might be associated with differences in milk production between
      Holstein cows and cows from Nellore breeds. However, the lack of difference
      between Nellore and Dairy Nellore suggests that other sequence variantions that
      regulate milk production might be responsible for the selection of Dairy Nellore
      cows with superior milk production.

PMID- 18607793
TI  - Using adaptive tests for the analysis of repeated measurements.
AB  - Several methods have been proposed for the analysis of data obtained from
      experimental units that are observed at multiple time points. In this paper we
      evaluate the performance of an adaptive test for the interaction of group and
      time, and an adaptive test for the group effect with data sets having
      measurements at common time points on two groups of experimental units. The
      results from extensive simulation studies show that the adaptive tests maintain
      their level of significance and are often more powerful than the corresponding
      likelihood ratio and mixed model tests when the error distributions and the
      random effect distributions are nonnormal. When the distributions are normal, the
      adaptive tests are nearly as powerful as the other tests.

PMID- 18607794
TI  - Clinical trials simulation: a statistical approach.
AB  - A generic template for clinical trials simulations that are typically required by
      statisticians is developed. Realistic clinical trials data sets are created using
      a unifying model that allows general correlation structures for
      endpoint*timepoint data and nonnormal distributions (including time-to-event),
      and computationally efficient algorithms are presented. The model allows for
      patient dropout and noncompliance. A grid-enabled SAS-based system has been
      developed to implement this model; details are presented summarizing the system
      development. An example illustrating use of the system is given.

PMID- 18607795
TI  - Accounting for interim safety monitoring of an adverse event upon termination of
      a clinical trial.
AB  - Upon termination of a clinical trial that uses interim evaluations to determine
      whether the trial can be stopped, a proper statistical analysis must account for
      the interim evaluations. For example, in a group-sequential design where the
      efficacy of a treatment regimen is evaluated at interim stages, and the
      opportunity to stop the trial based on positive efficacy findings exists, the
      terminal p-value, point estimate, and confidence limits of the outcome of
      interest must be adjusted to eliminate bias. While it is standard practice to
      adjust terminal statistical analyses due to opportunities to stop for "positive"
      findings, adjusting due to opportunities to stop for "negative" findings is also
      important. Stopping rules for negative findings are particularly useful when
      monitoring a specific rare serious adverse event in trials designed to show
      safety with respect to the event. In these settings, establishing conservative
      stopping rules are appropriate, and therefore accounting for the interim
      monitoring can have a substantial effect on the final results. Here I present a
      method to account for interim safety monitoring and illustrate its usefulness.
      The method is demonstrated to have advantages over methodology that does not
      account for interim monitoring.

PMID- 18607799
TI  - Compound optimal design criteria for nonlinear models.
AB  - Three approaches for combining parameter estimation with opposing design criteria
      are proposed for nonlinear models. The first method discussed is the technique
      found in the literature and as such is the reference method for this paper. The
      compound crtierion is formed by maximizing a weighted product of efficiencies.
      The second criterion involves maximizing an opposing criterion while minimizing a
      defined loss function. The third method simultaneously maximizes both
      efficiencies with respect to parameter estimation and an opposing criterion with
      a multiple objective simulated annealing algorithm. The examples presented are
      based on a PK-model and a generalized linear model found in the literature.

PMID- 18607800
TI  - Analytical expressions for combining population pharmacokinetic parameters from
      different studies.
AB  - We provide a set of formulas that allow the combination of separately performed
      analyses of population pharmacokinetic (PK) studies, without any further
      computational effort. More specifically, given the point estimates and
      uncertainties of two population PK analyses, the formulas provide the point
      estimates and uncertainties of the combined analysis, including the mean
      population values, the between-subject variability, and the residual variability.
      To derive the formulas we considered distributional assumptions applicable for
      the conjugate priors of the Bayesian problem of "unknown mean and variance." In
      order to demonstrate the approach, the formulas were applied to an example
      involving the results of fitting two real experimental datasets. The formulas
      presented offer an easy-to-use method of combining different analyses
      particularly applicable to a combination of literature information.

PMID- 18607801
TI  - On statistical evaluation of the linearity in assay validation.
AB  - Linearity is one of the most important characteristics for evaluation of the
      accuracy in assay validation. The current statistical method for evaluation of
      the linearity recommended by the Clinical Laboratory Standard Institute (CLSI)
      guideline EP6-A is reviewed. The method directly compares the point estimates
      with the pre-specified allowable limit and completely ignores the sampling error
      of the point estimates. An alternative method for evaluation of linearity,
      proposed by Kroll et al. (2000), considers the statistical test procedure based
      on the average deviation from linearity (ADL). However this procedure is based on
      an inappropriate formulation of hypotheses for the evaluation of linearity.
      Consequently, the type I error rates of both current methods may be inflated for
      inference of linearity. To claim the linearity of analytical methods, we propose
      that the hypothesis of proving the linearity should be formulated as the
      alternative hypothesis. Furthermore, any procedures for assessment of linearity
      should be based on the sampling distributions of the proposed test statistics.
      Therefore, we propose a two one-sided test (TOST) procedure and a corrected
      Kroll's procedure. The simulation studies were conducted to empirically compare
      the size and power between current and proposed methods. The simulation results
      show that the proposed methods not only adequately control size but also provide
      sufficient power. A numeric example illustrates the proposed methods.

PMID- 18607802
TI  - Generalizability in nongaussian longitudinal clinical trial data based on
      generalized linear mixed models.
AB  - This work investigates how generalizability, an extension of reliability, can be
      defined and estimated based on longitudinal data sequences resulting from, for
      example, clinical studies. Useful and intuitive approximate expressions are
      derived based on generalized linear mixed models. Data from four double-blind,
      randomized clinical trials into schizophrenia motivate the research and are used
      to estimate generalizability for a binary response parameter.

PMID- 18607803
TI  - Inference and sample size calculation in the fit assessment of filtering
      facepiece respirators.
AB  - Filtering facepiece respirators have recently been cleared by the U.S. Food and
      Drug Administration (FDA) for use by the general public in public health medical
      emergencies such as pandemic influenza. In the fit assessment of these devices it
      is important to distinguish between the two sources of variability: population
      heterogeneity and random fluctuations over repeated donnings. The FDA Special
      Controls Guidance Document (SCGD) which describes these devices and their
      evaluation, recommends that the fit performance of a filtering facepiece
      respirator be evaluated in terms of the proportion of users who will receive a
      specified level of protection 95% of the time. A point estimator of this
      proportion is easily obtained under an analysis of variance model, and the SCGD
      suggests bootstrap as one possible approach to interval estimation. This paper
      describes a closed-form procedure to obtain confidence intervals and provides
      sample size formulas. Simulation results suggest that the proposed procedure
      performs well in realistic settings and compares favorably to two simple
      bootstrap procedures.

PMID- 18607804
TI  - On methods to utilize HIV-RNA data measured by two different PCR assays.
AB  - The plasma HIV-RNA level has been used as the primary efficacy measurement in
      clinical trials to evaluate antiretroviral regimens in HIV-infected patients. It
      is measured by polymerase chain reaction (PCR) assays, which usually have limits
      of reliable quantification (LoQ). For example, the commercially available
      Amplicor Standard assay has a reliable range of 400-750,000 copies/mL while the
      Ultrasensitive assay has a range of 50-75,000 copies/mL. Values below the lower
      LoQ are usually reported as categorical variables such as " < 400 copies/mL" for
      the Standard assay and " < 50 copies/mL" for the Ultrasensitive assay. The
      Standard assay, which has a higher ceiling of 750,000 copies/mL, is typically
      used as the first tool to measure HIV-RNA levels; if a value of " < 400
      copies/mL" is reported by the Standard assay, the plasma sample may be re-tested
      by the Ultrasensitive assay, which has a lower LoQ of 50 copies/mL, in an effort
      to quantify the HIV-RNA level. However, for the calculation of change from
      baseline in log10 HIV-RNA, which is an important efficacy endpoint, the
      additional data measured by the Ultrasensitive assay are usually ignored due to a
      lack of simple and appropriate statistical methods. The conventional approach,
      which only uses the Standard assay data, may result in loss of information; the
      naive approach, which simply replaces " < 400 copies/mL" reported by the Standard
      assay with corresponding Ultrasensitive assay results, may lead to a biased
      estimate because the two assays may have different assay variability; the
      likelihood-based approach, which can utilize all data from both assays, is
      computationally intensive and requires a large sample size, which may limit its
      use in practice. In this paper, we propose a simple imputation approach that,
      unlike the naive method, accounts for the different variability in the two
      assays. A simulation study is used to compare these approaches. An example from a
      clinical trial in HIV-infected patients is used to illustrate the proposed
      approach.

PMID- 18607805
TI  - A safety monitoring procedure for a clinical drug development program, with
      application to the assessment of a novel COX-2 inhibitor.
AB  - Formal safety monitoring procedures are well-developed for use in individual
      clinical trials and provide valuable guidance to Independent Data Monitoring
      Committees (IDMCs). Less has been written about procedures for use over the whole
      of a drug development program. It is becoming common for a single IDMC to be
      appointed for a whole series of studies involving a single compound. While each
      study will have its own goals in terms of efficacy, safety, or both, there is the
      potential for all of them to contribute to an emerging picture of safety. Indeed,
      an IDMC overseeing several studies will need to integrate the data coming from
      each and a formal pre-defined approach can be a valuable aid. Formal procedures
      are especially relevant in situations where one or two undesirable events are
      recognized from the outset as being of particular concern. In some cases this
      might be death, and in the example discussed here it is a cardiovascular event of
      the type that has been found to be related to certain COX-2 inhibitors. In this
      paper a design proposal for a safety monitoring procedure for use by an IDMC
      during the development of a new COX-2 inhibitor will be described.

PMID- 18607806
TI  - Cumulative statistical power for hierarchical comparisons to evaluate two
      combination drug doses.
AB  - According to the regulatory requirements for multiple-dose factorial designs, a
      combination drug must have confirmatory evidence for being more effective than
      each component drug alone. An incomplete factorial design may be employed to
      evaluate some combination drugs because of resource constraints and priorities.
      In this paper, we compare the powers for four different patterns of sample size
      allocations in two incomplete factorial designs, with two combination drug doses
      and fixed total sample size. A hierarchical closed testing procedure is employed
      for the treatment comparisons of interest as a method to control type I error for
      multiple comparisons. The overall cumulative powers of contradicting all null
      hypotheses at a particular stage of the hierarchy and all preceding stages are
      determined by simulation for the respective stages of the hierarchy. The purpose
      is to identify the allocation of sample size so as to enable better power in a
      hierarchical evaluation of comparisons.

PMID- 18607807
TI  - A method for constructing and estimating the RR-memory of the QT-interval and its
      inclusion in a multivariate biomarker for torsades de pointes risk.
AB  - The problem of drug-induced QT-interval prolongation has become a major economic
      and health issue in the pharmaceutical industry. Little has been done to link
      analytically the QT-interval prolongation and the risk of torsades de pointes.
      This paper introduces a method for analyzing the dynamic characteristics of a 24
      hour electrocardiograph and offers an algorithm to measure the long-term memory
      of the RR-interval history in a single statistic. The memory statistic seems to
      improve the discrimination between healthy normal subjects and arrhythmia cases
      using only beat-to-beat information from the QT and RR intervals producing an
      impulse response function, which is completely independent of heart rate.

PMID- 18607811
TI  - Can a transitional work grant program in a workers' compensation system reduce
      cost and facilitate return to work?
AB  - Although previous research has shown returning the injured worker to work as soon
      as possible is important to the long-term prospects of the worker remaining in
      the work force, there is limited economic support for implementing such programs.
      Thus, the purpose of this case control study was to determine the cost savings of
      the implementation of a Transitional Work Grant (TWG) program, which consisted of
      several components including job analyses, education, communication and
      transitional work (TW). Companies that enrolled in the TWG program were matched
      to nonparticipating companies (NTW) based on employer size, type of industry,
      number of overall claims, and number of claims with > 7 days lost time (LT
      claims) submitted the year prior to enrollment. The study analyzed economic data:
      number of claims, number of LT claims, indemnity costs, medical costs, and days
      lost (days away from the workplace). An additional outcome was the ratio of LT
      claims (> 7 days lost work) to medical only (MO) claims (LT/MO ratio). Overall,
      participation in the TWG program was associated with decreased indemnity cost and
      decreased LT/MO ratio. However, effectiveness of the program varied by employer
      size and industry. In terms of the state of Ohio, these costs translate into
      substantial savings: more than $2.3 million per year. Although the cost savings
      and reduction in lost time claims is encouraging, the true benefit of TW has yet
      to be completely quantified. Future work must account for other potential co
      factors and programs that could also contribute to the savings as well as
      document further the indirect benefits associated with a TWG program, such as
      improved employee morale and increased productivity and product quality that
      could be four times greater than the direct savings. In summary, programs such as
      this one adopted by several companies in Ohio can reduce the cost burden of
      injuries.

PMID- 18607812
TI  - Filtration performance of NIOSH-approved N95 and P100 filtering facepiece
      respirators against 4 to 30 nanometer-size nanoparticles.
AB  - This study investigated the filtration performance of NIOSH-approved N95 and P100
      filtering facepiece respirators (FFR) against six different monodisperse silver
      aerosol particles in the range of 4-30 nm diameter. A particle test system was
      developed and standardized for measuring the penetration of monodisperse silver
      particles. For respirator testing, five models of N95 and two models of P100
      filtering facepiece respirators were challenged with monodisperse silver aerosol
      particles of 4, 8, 12, 16, 20, and 30 nm at 85 L/min flow rate and percentage
      penetrations were measured. Consistent with single-fiber filtration theory, N95
      and P100 respirators challenged with silver monodisperse particles showed a
      decrease in percentage penetration with a decrease in particle diameter down to 4
      nm. Penetrations less than 1 particle/30 min for 4-8 nm particles for one P100
      respirator model, and 4-12 nm particles for the other P100 model, were observed.
      Experiments were also carried out with larger than 20 nm monodisperse NaCl
      particles using a TSI 3160 Fractional Efficiency Tester. NaCl aerosol penetration
      levels of 20 nm and 30 nm (overlapping sizes) particles were compared with silver
      aerosols of the same sizes by a three-way ANOVA analysis. A significant (p <
      0.001) difference between NaCl and silver aerosol penetration levels was obtained
      after adjusting for particle sizes and manufacturers. A significant (p = 0.001)
      interaction with manufacturers indicated the difference in NaCl, and silver
      aerosol penetrations were not the same across manufacturers. The two aerosols had
      the same effect across 20 nm and 30 nm sizes as shown by the absence of any
      significant (p = 0.163) interaction with particle sizes. In the case of P100
      FFRs, a significant (p < 0.001) difference between NaCl and silver aerosol (20 nm
      and 30 nm) penetrations was observed for both respirator models tested. The
      filtration data for 4-30 nm monodisperse particles supports previous studies that
      indicate NIOSH-approved air-purifying respirators provide expected levels of
      filtration protection against nanoparticles.

PMID- 18607813
TI  - Urinary incontinence after gynecologic cancer treatment.

PMID- 18607814
TI  - The influence of lunar cycle on frequency of birth, birth complications, neonatal
      outcome and the gender: a retrospective analysis.
AB  - OBJECTIVE: The relation of lunar phases to the birth rate has been the focus of
      considerable research with still controversial results. The purpose of this study
      was to examine the influence of the lunar cycle on the frequency of birth, on
      instrumental delivery, neonatal outcome as well as a possible relationship
      between lunar position at time of conception and the gender of the child.
      MATERIAL AND METHODS: Six thousand seven hundred and twenty five deliveries were
      retrospectively analyzed from 01 January 2000 to 31 December 2006 at the
      Department of Obstetrics and Gynaecology of the University Medical School of
      Hannover. Inclusion criteria were: spontaneous vaginal births without induction,
      vacuum and forceps extractions as well as non-elective cesarean sections, all
      cases without labor induction. Exact lunar phases were determined by means of
      birthday and birth time by a specific computer software. RESULTS: The analysis
      revealed no significant correlation of birth rate to lunar phases. There were
      also no significant differences regarding birth complications, neonatal outcome
      and gender to the lunar cycle at the time of conception. CONCLUSION: There is no
      predictable influence of the lunar cycle on deliveries or delivery complications
      nor to the gender of the baby. As expected and in agreement with some recent
      studies this pervasive myth is not evidence based.

PMID- 18607815
TI  - Expression of adhesion molecules in first trimester spontaneous abortions and
      their role in abortion pathogenesis.
AB  - BACKGROUND: Early placental development is associated with complex regulatory
      mechanisms, and molecular communication problems that arise during the
      developmental process are dangerous for continuation of the pregnancy. As studies
      on the process of invasion and migration of trophoblast cells have shown the
      importance of cell-cell and cell-matrix interactions, we examined the effects of
      adhesion molecules on the mechanism(s) of spontaneous abortions and compared them
      to elective abortion materials using histopathological and immunohistochemical
      methods. To the best of our knowledge, this is the first study to investigate
      adhesion molecules in spontaneous abortions. METHODS: Curettage materials from
      abortions were examined retrospectively in the Department of Pathology, Zonguldak
      Karaelmas University School of Medicine, Zonguldak, Turkey. CD31/PECAM-1
      (endothelial cell marker), CD44v (variant 3), E-cadherin, CD54/ICAM-1, and
      CD106/VCAM-1 expression profiles were evaluated by immunohistochemistry, and
      cellular localization was determined under light microscopy. The results of
      spontaneous abortions were compared to those of elective abortions. RESULTS: The
      staining percentages of CD31, CD44, CD106, and E-cadherin decreased in cases of
      spontaneous abortion, but CD54 (ICAM-1) expression increased. Statistically
      significant differences were detected between spontaneous and elective abortion
      materials with regard to cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and
      extravillous trophoblasts (EVTs) with the anti-CD31 antibody (p=0.0001). In
      addition, CD54 (p=0.007 and p=0.002) and E-cadherin (p=0.002 and p=0.02)
      expression in CTs and STs, respectively, were significantly different.
      Furthermore, CD44 expression (p=0.003) in decidual (D) cells and CD106 (p=0.0001)
      expression in vessels of endometrial (E) and villous tissues were also
      significantly different. CONCLUSIONS: Decreased CD31 expression in CTs that
      invade the spiral arterioles and mimic E cells in spontaneous abortion cases
      suggests that CD31/PECAM-1 is an important molecule in uteroplacental adequacy.
      Moreover, diminished expression of CD44 in D cells caused impaired stroma-villous
      connections. Enhancement of ICAM-1 in placental and invading STs may be useful as
      a diagnostic marker for patients who may have a tendency to have spontaneous
      abortions. A down-regulation of E-cadherin was observed, which may be responsible
      for impaired CT differentiation and loss of the pregnancy. Furthermore, decreased
      VCAM-1 expression in spontaneous abortions may be consistent with the importance
      of VCAM-1 in trophoblast-endothelial cell interactions. Many adhesion molecules
      are known to be effective in the normal development of a pregnancy, and the
      analysis of adhesion molecules in spontaneous abortions will provide useful
      information for clarifying the physiopathology of spontaneous abortions.

PMID- 18607816
TI  - Hormonal carcinogenesis and socio-biological development factors in endometrial
      cancer: a clinical review.
AB  - OBJECTIVE: Endometrial cancer is one of the most common invasive gynecologic
      malignancies in developed countries and the eighth leading cause of cancer death
      in women; it typically arises in the sixth or seventh decade of life. The aim of
      this review was to evaluate possible roles of genetic and socio-biological
      factors in type I endometrial cancer, largely confined to pre- and perimenopausal
      women, with a history of estrogen exposure and/or endometrial hyperplasia.
      METHODS: An extensive literature review, from 1990 to 2007 was performed on
      modifiable risk factors for type I endometrial cancer. Additionally,
      carcinogenesis mechanisms, biomarker and hormonal and biomolecular approaches to
      cancer detection, progression and monitoring and socio-biological factors were
      reviewed. RESULTS: Several socio-biological and lifestyle characteristics, such
      as hormone replacement therapy, glycemic index, obesity, alcohol use,
      antipsychotic medication, melatonin, physical activity and variants in hormone
      metabolism genes have been identified as risk factors for developing endometrial
      cancer of type I, the majority of which are associated with excess estrogens
      causing continued stimulation of the endometrium. There is a genetic link to non
      polyposis colorectal cancer syndrome, but association of endometrial cancer risk
      to other genetic polymorphisms has yielded conflicting results. CONCLUSIONS: Many
      factors linked to hormonal imbalance, such as obesity, weight change, body size,
      alcohol, hyper-androgenic states, glycemic index and antidepressant agents,
      influence the endometrial cancer risk, central to which are endogenous and
      exogenous estrogen hyperstimulation of the endometrium. Conversely, smoking
      cigarettes, diet, physical activity and melatonin production seem to reduce the
      risk of cancer development. Other external factors fit well with the unopposed
      estrogen theory, but more studies are needed to investigate modifiable and added
      risk factors for endometrial cancer.

PMID- 18607817
TI  - Acidemia at birth, related to obstetric characteristics and to oxytocin use,
      during the last two hours of labor.
AB  - OBJECTIVE: Evaluate obstetric characteristics during the last two hours of labor
      in neonates born with acidemia. DESIGN: Case-control study. SETTING: Delivery
      units at two university hospitals in Sweden. STUDY POPULATION: Out of 28,486
      deliveries during 1994-2004, 305 neonates had an umbilical artery pH value <7.05
      at birth. METHODS:  CASES: neonates with an umbilical artery pH < 7.05. Controls
      were neonates with pH > or = 7.05 and an Apgar score > or =7 at 5 minutes.
      Obstetric characteristics, cardiotocographic patterns and oxytocin treatment
      during the last two hours of labor were recorded. RESULTS: In the univariate
      analysis, > or =6 contractions/10 minutes (odds ratio (OR) 4.94, 95% confidence
      interval (CI) 3.25-7.49), oxytocin use (OR 2.20, 95% CI 1.66-2.92), bearing down
      > or =45 minutes (OR 1.77, 95% CI 1.31-2.38) and occipito-posterior position (OR
      2.18, 95% CI 1.19-3.98) were associated with acidemia at birth. In the
      multivariate analysis, only > or =6 contractions/10 minutes (OR 5.36, 95% CI 3.32
      8.65) and oxytocin use (OR 1.89, 95% CI 1.21-2.97) were associated with acidemia
      at birth. Among cases with > or =6 contractions/10 minutes, 75% had been treated
      with oxytocin. Pathological cardiotocographic patterns occurred in 68.8% of cases
      and in 26.1% of controls (p<0.001). CONCLUSION: A hyperactive uterine contraction
      pattern and oxytocin use are the most important risk factors for acidemia at
      birth. The increased uterine activity was related to overstimulation in the
      majority of cases. The duration of bearing down is less important when uterine
      contraction frequency has been considered.

PMID- 18607818
TI  - Outcome of planned home births compared to hospital births in Sweden between 1992
      and 2004. A population-based register study.
AB  - OBJECTIVE: The aim of this population-based study was to measure the risk of
      adverse outcome for mother and child in planned home births in a Swedish
      population irrespective of where the birth actually occurred, at home or in
      hospital after transfer. DESIGN: A population-based study using data from the
      Swedish Medical Birth Register. SETTING: Sweden 1992-2004. PARTICIPANTS: A total
      of 897 planned home births were compared with a randomly selected group of 11,341
      planned hospital births. MAIN OUTCOME MEASURES: Prevalence of mortality and
      morbidity among mothers and children, emergency conditions, instrumental and
      operative delivery and perineal lacerations were compared. RESULTS: During this
      period in Sweden the neonatal mortality rate was 2.2 per thousand in the home
      birth group and 0.7 in the hospital group (RR 3.6, 95% CI 0.2-14.7). No cases of
      emergency complications were found in the home birth group. The risk of having a
      sphincter rupture was lower in the planned home birth group (RR 0.2, 95% CI 0.0
      0.7). The risk of having a cesarean section (RR 0.4, 95% CI 0.2-0.7) or
      instrumental delivery (RR 0.3, 95% CI 0.2-0.5) was significantly lower in the
      planned home birth group. CONCLUSION: In Sweden, between 1992 and 2004, the
      intrapartum and neonatal mortality in planned home births was 2.2 per thousand.
      The proportion is higher compared to hospital births but no statistically
      significant difference was found. Women in the home birth group more often
      experienced a spontaneous birth without medical intervention and were less likely
      to sustain pelvic floor injuries.

PMID- 18607819
TI  - Direct maternal deaths in Norway 1976-1995.
AB  - AIMS: To report direct maternal mortality ratio (MMR) in Norway between 1976 and
      1995 including a description of the underlying complications in pregnancy, the
      causes of death and assessment of standard of care. METHODS: The maternal deaths
      were identified through the Cause of Death Registry, Statistics Norway, and
      Medical Birth Registry of Norway. We requested copies of the hospital case
      records and the maternal death autopsies. The direct maternal deaths were
      classified on the basis underlying causes and assessed for substandard care
      according to the guidelines at the time of death and preventability provided
      optimal conditions and up to date guidelines. RESULTS: In the period 1976-1995 we
      identified 61 direct maternal deaths in Norway. The direct MMR was 5.5/100,000
      births. Sufficient information was available for analysis in 51 of these cases.
      Six deaths occurred in early pregnancy. Among the 45 women who gave birth, 32 had
      a cesarean section, and the death was judged to be related to a complication of
      the operation in more than half of these cases. The standard of care and the
      possibility of preventing death were evaluated in 49 cases. Substandard care was
      observed in 21 of them and 27 were considered avoidable or potentially avoidable.
      CONCLUSION: The direct MMR in Norway was 5.5/100,000 births. The main causes were
      complications of hypertensive disease of pregnancy and thromboembolism. The
      majority of maternal deaths were associated with cesarean delivery and considered
      potentially avoidable.

PMID- 18607821
TI  - Sexual assault centers: attendance rates, and differences between early and late
      presenting cases.
AB  - OBJECTIVE: Sexual assault centers (SACs) aim at assisting victims and to provide
      forensic medical examination (FME). This study explores the gap between assaults
      actually occurring and those seen at SAC; and the characteristics of cases
      presented in time/too late for FME (early and late cohorts). DESIGN: Retrograde
      descriptive study. SETTING AND SAMPLE: A two-year series from a self-referral
      SAC; characteristics of victims, assaults, use of services. METHODS: Chi
      quadrate, uni- and multivariate logistic regression analyses. MAIN OUTCOME
      MEASURES: Number of female victims seen/female at-risk population (attendance
      rates). Case and service profiles in the two cohorts. Adjusted odds for late
      presentation. RESULTS: Attendance rates for females were 0.12% (14-55 years); an
      estimated 4-7% of sexually assaulted females in the catchment area. Two hundred
      and seventy eight victims arrived in time for FME, 76 later; 6% males. Assaults
      in the early cohort were more often performed by strangers. Two hundred and
      thirty-eight victims underwent FME, 55% complied with follow-up, 55% reported to
      the police. The late cohort contained more adolescent victims, more
      acquainted/partner perpetrators, more verbal coercion; 45% medically examined,
      80% follow-up compliance; 34% reported to police. Further referrals occurred
      equally often in both cohorts; 12% to somatic and 39% to psychiatric services.
      Among victims seen, 5% died within 7 years of consultation. CONCLUSION: Cases
      seen at SAC are strongly selected. The late cohort seems more representative of
      the commonly occurring assaults; young victims, known assailants. Even late
      presenters are in need of a multidisciplinary approach.

PMID- 18607822
TI  - Female genital mutilation among antenatal care and contraceptive advice attendees
      in Sweden.
AB  - OBJECTIVE: To explore knowledge of, attitudes toward and practice of female
      genital mutilation (FGM) among women originally from countries where FGM is
      customary attending antenatal care and contraceptive advice in Sweden. METHODS:
      Women in reproductive age living in Sweden who originate from countries where FGM
      is practiced coming for antenatal care or contraceptive advice at two maternity
      welfare centers in Stockholm were asked to participate. Interview administered
      questionnaires and gynecological examination were used for data collection. The
      data were analyzed by descriptive statistics. RESULTS: Out of 49 women asked, 40
      women agreed to participate, of whom 37 had undergone FGM. Most FGM operations
      had been performed by doctors or midwives. Half of the Muslim women said FGM was
      allowed by their religion. All women reporting to have undergone 'sunna', an
      allegedly mild form, had extensive damage to their genitals. At gynecological
      examination three cases of reinfibulation were detected, of which two had been
      performed after delivery in Sweden. Twenty-nine women had daughters and three had
      let their daughters undergo FGM, all of them before settling in Sweden. Problems
      related to delivery and sexual intercourse were the most commonly mentioned
      complications of FGM. CONCLUSIONS: The reliability of the self-reported form of
      FGM is low, which may have implications for research, interventions and health
      care. Although many women express negative attitudes toward FGM and know about
      serious complications, the religious justifications, the practice of FGM on
      daughters, reinfibulation on adults and medicalization of the practice indicate
      attitudes that favor of the continued practice of FGM.

PMID- 18607823
TI  - Modern management of uterine fibroids.
AB  - Uterine fibroids are the most common tumor of the reproductive tract in women of
      reproductive age. Although they are benign tumors that are often asymptomatic,
      uterine fibroids may cause debilitating symptoms in many women, such as abnormal
      uterine bleeding, abdominal pain, increased abdominal girth, urinary frequency,
      constipation, pregnancy loss, dyspareunia, and in some cases infertility. Several
      approaches are available for the treatment of uterine fibroids. These include
      pharmacologic options, such as hormonal therapies and gonadotropin-releasing
      hormone agonists; surgical approaches, such as hysterectomy, myomectomy,
      myolysis, laparoscopic uterine artery occlusion, magnetic resonance imaging
      guided focused ultrasound surgery, and uterine artery embolization. The choice of
      approach may be dictated by factors such as the patient's desire to become
      pregnant in the future, the importance of uterine preservation, symptom severity,
      and tumor characteristics. New treatment options for uterine fibroids would be
      minimally invasive, have long-term data demonstrating efficacy and safety, have
      minimal or no incidence of fibroid recurrence, be easy to perform, preserve
      fertility, and be cost effective. New treatment approaches are under
      investigation, with the goals of being effective, safe, and less invasive.

PMID- 18607824
TI  - Alcohol use before and during pregnancy and factors influencing change among
      Swedish women.
AB  - OBJECTIVE: To investigate alcohol intake during pregnancy among women, to assess
      health cares providers' advice to the women and the relative importance of
      different factors on changes in the women's drinking. DESIGN: Questionnaire
      study. SETTING: Linkoping, Sweden. POPULATION: A total number of 1,533 women
      registered at a maternity health care center in Linkoping during a one-year
      period, from 1 April 2005 to 31 March 2006. METHODS: Mailed anonymous
      questionnaire with a response rate of 61%. MAIN OUTCOME MEASURES: Drinking
      behavior and information sources. RESULTS: During pregnancy, 94% (n=869) of the
      responding women abstained from alcohol, including 13% (n=117) who were already
      abstainers. Six percent (n=55) continued drinking during the pregnancy. Those who
      continued drinking during pregnancy were older, had more often given birth and
      drank more frequently before pregnancy than the women who abstained. Half of the
      respondents (n=428) believed that decreases in alcohol intake during pregnancy
      reported in previous studies could be due to inaccurate self-reporting. The main
      message from maternity health care providers was perceived to be complete
      abstinence from alcohol during pregnancy (85%; n=777), although 8% (n=76) claimed
      that they had not received any advice regarding this. Media attention concerning
      risks associated with drinking during pregnancy was seen as slightly more
      important to achieve reduced alcohol intake during pregnancy than advice from
      maternity health care providers. CONCLUSIONS: A majority of women in this study
      reported abstaining from alcohol during pregnancy.

PMID- 18607825
TI  - Donor insemination and parenting: concerns and strategies of lesbian couples. A
      review of international studies.
AB  - The concerns and strategies of lesbian couples at the time of donor insemination,
      throughout pregnancy and during early parenthood differ in several ways from
      those of heterosexual couples. For the majority of the lesbian couples
      insemination was the first option to conceive. They reported having strategies
      for their children growing up in a heteronormative society, and the parents
      shared time with and responsibility for the children equally. Issues considered
      most important by the couple were an open and non-judgmental attitude from
      caregivers without heteronormative assumptions, knowledge about lesbian women's
      situation and acknowledgement of the co-mother.

PMID- 18607826
TI  - Usefulness of extraperitoneal laparoscopic paraaortic lymphadenectomy for lymph
      node recurrence in gynecologic malignancy.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and feasibility of
      extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected lymph node
      recurrence of gynecological cancers. DESIGN: Descriptive study. SETTING: Unit of
      Gynecologic Oncology of an acute-care teaching hospital in Barcelona, Spain.
      POPULATION: Between December 2002 and October 2007, eight women underwent
      extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected lymph node
      recurrence, detected by magnetic resonance image (MRI), computed tomography (CT)
      scan or 18F-fluorodeoxyglucose positron emission tomography (PET) scanning. The
      suspicious nodes were removed through an extraperitoneal laparoscopic approach.
      RESULTS: The median age of patients was 66.5 years (range: 54-74). The median
      operating time was 157.5 minutes (range: 120-240). The median blood loss was
      112.5 mL (range: 50-150). The mean nodal yield was 9.4+/-4.72 (range: 1-16).
      There were no intraoperative or postoperative complications. The median hospital
      stay was two days. Histological examination revealed metastasis in seven of eight
      patients. CONCLUSIONS: The extraperitoneal laparoscopic paraaortic
      lymphadenectomy for lymph node recurrence of gynecological cancers is a safe and
      feasible procedure which should be considered where there is isolated involvement
      of retroperitoneal lymph nodes. This procedure is a minimally invasive technique
      that allows an excellent approach to the paraaortic lymph nodes.

PMID- 18607827
TI  - Is serum-soluble vascular endothelial growth factor receptor-1 of importance in
      unexplained infertility?
AB  - OBJECTIVE: To analyze the role of vascular endothelial growth factor (VEGF) and
      its naturally occurring circulating antagonist, soluble VEGF receptor-1 (sVEGFR
      1), in infertility. VEGF is a key angiogenic factor in the endometrial and
      ovarian cyclic processes that are crucial for fertility and sVEGFR-1 impairs its
      function and fertility in animals - less is known as regards human fertility.
      DESIGN: Case-control study. SETTING: University Central Hospital, a tertiary
      referral center. POPULATION: Women with unexplained infertility (n=15) and
      fertile controls (n=10) had serial blood samples collected during their natural
      cycles, and the infertile women during a subsequent in vitro fertilization (IVF)
      cycle. METHODS: Enzyme-linked immunosorbent assay was used for this study. MAIN
      OUTCOME MEASURES: Concentrations of VEGF and sVEGFR-1 in the natural cycles and
      of sVEGFR-1 during a subsequent IVF cycle. RESULTS: Plasma VEGF concentrations
      showed no cyclicity in fertile women, but were higher in the infertile group at
      the midluteal phase. Serum sVEGFR-1 concentrations were similar between the
      groups and between natural and IVF cycles. However, in infertile women,
      concentrations of sVEGFR-1 increased from the follicular phase to the luteal
      phase. In the follicular phase infertile women had a high ratio of VEGF/sVEGFR-1,
      which was decreased in the luteal phase. Both findings were associated with
      failure to achieve pregnancy in subsequent IVF cycles. CONCLUSIONS: One cause of
      unexplained infertility may be unbalanced secretion of sVEGFR-1 with concomitant
      changes in free VEGF during the transition from the follicular to the luteal
      phase. This aberration may be related to impaired implantation.

PMID- 18607828
TI  - The challenges of diagnosis and treatment of malaria in pregnancy in low resource
      settings.
AB  - Malarial infestation in pregnancy is a major public health concern in endemic
      countries and ranks high amongst the commonest complications of pregnancy,
      especially in large areas of Africa and Asia. It is an important preventable
      cause of significant maternal morbidity and mortality with associated fetal as
      well as perinatal wastage. The burden of malaria is greatest in sub-Saharan
      Africa where it contributes directly or indirectly to maternal and perinatal
      morbidity and mortality. The need for prompt and accurate diagnosis as well as
      prevention and treatment of malaria during pregnancy cannot, therefore, be
      overemphasized. This commentary focuses on the challenges of diagnosis and
      treatment of malaria in pregnancy.

PMID- 18607829
TI  - Endoglin, PlGF and sFlt-1 as markers for predicting pre-eclampsia.
AB  - OBJECTIVE: To evaluate the ability of endoglin, placental growth factor (PlGF)
      and the soluble form of vascular endothelial growth factor receptor (sFlt-1)
      measurements in gestational weeks 24-28 were used to predict pre-eclampsia.
      DESIGN: Observational, prospective study. Setting. Department of Gynecological,
      Obstetrical Sciences and Reproductive Medicine, University of Messina. Sample.
      Fifty-two pre-eclamptic and 52 healthy pregnant women. METHODS: A maternal serum
      sample was frozen and stored at 1-h 50-g glucose challenge test between 24 and 28
      weeks' gestation. A second maternal serum sample was collected at admission for
      the onset of the disease in the pre-eclamptic group and at admission for delivery
      in the control group. Levels of endoglin, sFlt-1 and the PlGF were measured in
      the stored serum. Pre-eclamptic subjects were also divided into women with early
      onset (<37 weeks) and women with late-onset pre-eclampsia (> or =37 weeks).
      RESULTS: Levels of endoglin, sFlt-1, and sFlt-1:PlGF ratio were found to be
      higher in the pre-eclamptic group in both trimesters. No differences were found
      between early- and late-onset pre-eclamptic. The Receiver Operating
      Characteristics curve, applied to the second trimester marker values, showed the
      best diagnostic profile for sFlt-1:PlGF (area under the curve, AUC=0.92) followed
      by endoglin (AUC=0.88), sFlt-1 (AUC=0.87) and PlGF (AUC=0.83). This finding was
      confirmed by Bayesian analysis which highlighted a specificity, a sensitivity, a
      diagnostic accuracy, a positive predictive value and a negative predictive value
      of 88.5% for sFlt-1:PlGF using a cut-off of 38.47. CONCLUSIONS: Endoglin, PlGF
      and sFlt-1 might be used as markers for predicting pre-eclampsia, but sFlt-1:PlGF
      seems to be more accurate.

PMID- 18607830
TI  - Dietary and lifestyle interventions to limit weight gain during pregnancy for
      obese or overweight women: a systematic review.
AB  - BACKGROUND: To assess the benefits and harm of dietary and lifestyle
      interventions during pregnancy to improve maternal and infant outcomes for
      pregnant women who are overweight or obese. METHODS: Randomized controlled trials
      comparing any form of dietary or lifestyle intervention during pregnancy for
      women who are overweight or obese with no treatment to improve maternal and
      infant health were considered. The Cochrane Controlled Trials Register (CENTRAL),
      PUBMED and the Australian and International Clinical Trials Registry were
      searched (date of last search November 2007). RESULTS: Two published trials were
      identified with no statistically significant differences identified between the
      intervention and standard care groups for maternal or infant health outcomes.
      CONCLUSION: There is limited information available assessing the benefits and
      harm associated with dietary and lifestyle interventions for overweight and obese
      pregnant women. Further evaluation through randomized trials with adequate power
      is required.

PMID- 18607831
TI  - Registration of Down syndrome in the Medical Birth Registry of Norway: validity
      and time trends.
AB  - OBJECTIVE: To validate Down syndrome registration in the Medical Birth Registry
      of Norway (MBRN), 2001-2005, and study time trends and geographical differences
      in Down syndrome prevalence,1967-2005. DESIGN/SETTING: Population-based cohort
      study, Norway. POPULATION: 2.3 million pregnancies and births registered in the
      MBRN, 1967-2005. METHODS: We linked data from the MBRN during 2001-2005 with data
      from Norway's four laboratories of medical genetics. We calculated sensitivity
      and positive predictive values (PPV) of the MBRN registration overall, and by
      background variables. Prevalence rates from 1967 to 2005, overall and regional,
      were presented graphically as smoothed lowess estimates, crude and standardized
      for maternal age. Time trends were evaluated, adjusting for maternal age by
      logistic regression. MAIN OUTCOME MEASURES: Sensitivity, PPV, and prevalence
      rates. RESULTS: Five hundred and seventy-six verified cases of Down syndrome gave
      a prevalence of 2.0 per 1,000 among 288,213 births and terminations in the MBRN
      during 2001-2005. Of verified cases, 470 (81.6%) were registered with Down
      syndrome in the MBRN, while 470 (90.2%) of 521 MBRN-registered cases were
      verified. Sensitivity was higher in the Northern (93.1%; p=0.005) and Middle
      (90.6%; p=0.02) region relative the Southern (76.3%), higher for mothers > or =35
      years (92.9%) than younger ones (86.1%; p=0.01), and higher for live births
      (88.8%) relative stillbirths (55.6%; p<0.001). When adjusting for maternal age,
      there were no significant time trends in prevalence rates from 1967 to 2005.
      Regional differences over time were found, probably representing reporting
      differences. CONCLUSIONS: Validity of registration in the MBRN was satisfactory
      during 2001-2005. Increasing prevalence rates over time were explained by
      increasing maternal age.

PMID- 18607833
TI  - Pregnant women's awareness and knowledge of mother-to-child transmission of HIV
      in South Central China.
AB  - OBJECTIVE: China has, in recent years, seen an increase in the number of HIV
      positive children due to the increase in number of HIV-positive women. The
      purpose of this study was to investigate the awareness and knowledge of mother-to
      child transmission of HIV and its prevention among pregnant women attending the
      antenatal clinics in South Central China. METHODS: The study was carried out in
      three antenatal clinics of three hospitals from February 2005 to March 2006, and
      it was based on personal interviews and questionnaires designed to assess the
      pregnant women's awareness about HIV/AIDS, evaluate their knowledge of possible
      routes of transmission, particularly mother-to-child transmission, and determine
      their familiarity with measures that prevent vertical transmission from mother to
      child. Two thousand three hundred and ninety pregnant women were included in the
      study. RESULTS: All individuals were aware of HIV/AIDS. The majority (91%) of
      those women were aware that HIV/AIDS can coexist with pregnancy but only 64% had
      heard about mother-to-child transmission. Transplacental route, vaginal delivery
      and breastfeeding were identified as routes of transmission from mother to child
      by 85%, 60% and 20% of respondents, respectively. Cesarean section was believed
      to be a route of transmission by 55% of respondents, but no one identified
      cesarean section as a method of prevention of mother-to-child transmission.
      CONCLUSIONS: The level of awareness and knowledge of HIV/AIDS among pregnant
      women attending our antenatal clinics seems to be superficial; more education and
      knowledge about mother-to-child transmission are needed in China.

PMID- 18607832
TI  - MMP-2, TIMP-1, E-cadherin, and beta-catenin expression in endometrial serous
      carcinoma compared with low-grade endometrial endometrioid carcinoma and
      proliferative endometrium.
AB  - OBJECTIVE: To investigate the expression of MMP-2, TIMP-1, E-cadherin and beta
      catenin in endometrial serous carcinoma (ESC), low-grade endometrial endometrioid
      carcinoma (EEC), and proliferative endometrium. METHODS: We performed an
      immunohistochemical study on 14 cases of ESC, 15 cases of low-grade EEC, and 10
      cases of proliferative endometrium. RESULTS: Compared with low-grade EEC, ESC
      showed significantly increased MMP-2 and TIMP-1 expression, as well as decreased
      membranous beta-catenin staining. E-cadherin expression was significantly lower
      in ESC and EEC as compared with proliferative endometrium. CONCLUSIONS: We
      suggest that MMP-2 and TIMP-1 expression and loss of beta-catenin have a role in
      the pathogenesis and progression of ESC. Decreased E-cadherin may have an
      important role in the development of both ESC and EEC. Furthermore, the
      dissimilarities in MMP-2, TIMP-1, E-cadherin and beta-catenin expressions in ESC
      compared with EEC may be responsible, along with other factors, for their
      different biological behavior.

PMID- 18607834
TI  - Influence of convergence angle and cement space on adaptation of zirconium
      dioxide ceramic copings.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the influence of
      total convergence angle and cement space on internal and marginal adaptation of
      posterior zirconium dioxide (zirconia) ceramic copings. MATERIAL AND METHODS:
      Seventy-two standardized mandibular first molar zirconia copings were fabricated
      with nine parameters: three different total convergence angles (6 degrees , 12
      degrees , and 20 degrees ) with three different computer-fixed cement spaces (10,
      30, and 60 microm). Marginal adaptation was assessed to measure vertical
      discrepancy between the coping and abutment by direct viewing. Internal
      adaptation was evaluated using the cement replica technique with a laser
      microscope. The Kruskal-Wallis test and Wilcoxon rank-sum test were performed to
      test for differences in internal space and marginal discrepancy values
      (alpha=0.05). RESULTS: The median of mean internal spaces/marginal discrepancies
      ranged from 54.0/27.4 to 128.1/77.8 microm. Statistically significant differences
      in the internal spaces were found between groups with 6 degrees and 20 degrees
      convergence angle, regardless of cement space. The different cement spaces did
      not have any significant influence on the 12 degrees and 20 degrees convergence
      angle groups. The 60-microm cement space group exhibited statistically smaller
      marginal discrepancies than the 10-microm cement space group in all the different
      convergence angles. CONCLUSIONS: Within the limitations of the present study, the
      internal spaces of zirconia ceramic copings may decrease as the convergence
      angles of abutments increase. The computer-fixed cement space might influence the
      marginal adaptation of zirconia ceramic copings. The internal and marginal
      adaptation of zirconia ceramic copings obtained was within the range of clinical
      acceptance.

PMID- 18607835
TI  - Impact of the in situ formed salivary pellicle on enamel and dentine erosion
      induced by different acids.
AB  - OBJECTIVE: To investigate and compare the protective impact of the in situ formed
      salivary pellicle on enamel and dentine erosion caused by different acids at pH
      2.6. METHODS: Bovine enamel and dentine samples were exposed for 120 min in the
      oral cavity of 10 healthy volunteers. Subsequently, enamel and dentine pellicle
      covered specimens were extraorally immersed in 1 ml hydrochloric, citric or
      phosphoric acid (pH 2.6, 60 s, each acid n=30 samples). Pellicle-free samples
      (each acid n=10) served as controls. Calcium release into the acid was determined
      by atomic absorption spectroscopy. The data were analysed by two-way ANOVA and
      Tukey's test (alpha=0.05). RESULTS: Pellicle-covered samples showed significantly
      less calcium loss compared to pellicle-free samples in all acid groups. The mean
      (SD) pellicle protection (% reduction of calcium loss) was significantly better
      for enamel samples [60.9 (5.3)] than for dentine samples [30.5 (5.0)], but
      revealed no differences among the acids. CONCLUSION: The efficacy of the in situ
      pellicle in reducing erosion was 2-fold better for enamel than for dentine.
      Protection of the pellicle was not influenced by the kind of acid when enamel and
      dentine erosion was performed at pH 2.6.

PMID- 18607836
TI  - Pemetrexed-associated radiation recall dermatitis.

PMID- 18607837
TI  - Liquid ionization chamber calibrated gel dosimetry in conformal stereotactic
      radiotherapy of brain lesions.
AB  - Hypofractionated conformal stereotactic radiotherapy (HCSRT) is an established
      method of treating brain lesions such as arteriovenous malformations (AVMs) and
      brain metastases. The aim of this study was to investigate the reliability of
      treatment plans in the terms of dose distribution and absorbed dose for HCSRT.
      METHODS AND MATERIALS: Treatment plans for three different clinical intracerebral
      targets, AVMs, were transferred to a CT study of a spherical water filled phantom
      simulating the human head and recalculated for the phantom geometry using a
      standard treatment planning system utilizing a pencil beam algorithm for dose
      calculation. The calculated absorbed dose, relative three dimensional (3D) dose
      distribution and dose conformity were investigated using gel dosimetry normalized
      to liquid ionization chamber (LIC) measurements. RESULTS: The measured absorbed
      dose to the dose reference point was found to be within 2% of the calculated dose
      for all three targets. The measured dose distribution was found to be within 3%
      and 2 mm of the calculated dose for more than 93% of all points in the target
      volume for all three targets. CONCLUSIONS: The results show that the investigated
      standard treatment planning system can correctly predict the absorbed dose and
      dose distribution in different types of intracerebral targets and that the
      treatment can be delivered according to the plan.

PMID- 18607838
TI  - Overexpression of cortactin in head and neck squamous cell carcinomas can be
      uncoupled from augmented EGF receptor expression.
AB  - BACKGROUND: The gene encoding cortactin, CTTN (locus 11q13), an actin-binding
      substrate of Src kinases, is frequently amplified in breast and head and neck
      squamous cell carcinomas (HNSCC) and cortactin overexpression is thought to
      contribute in a significant way to the invasive phenotype of these tumors.
      Elevated Epidermal Growth Factor receptor (EGFR) expression is also commonly
      observed in HNSCC and has been associated with poor prognosis and resistance to
      cytotoxic agents, including ionizing radiation. It has been suggested that
      cortactin overexpression may increase EGFR levels in these tumors by affecting
      receptor downregulation, however we recently found by multivariate analysis, that
      cortactin expression status remained an independent prognostic factor for local
      recurrence, disease-free survival, and overall survival. MATERIAL AND METHODS: To
      examine the potential link between cortactin overexpression and EGFR status, we
      compared cortactin and EGFR levels in a series of tumor lines derived from HNSCC.
      RNAi-mediated silencing was performed in cortactin overexpressing cells and in
      vivo tumoral potential with respect to cortactin and EGFR status was analyzed.
      RESULTS AND DISCUSSION: Cortactin and EGFR levels were not strictly coupled in
      these lines and cortactin depletion did not decrease steady state receptor
      levels, although it did affect the epithelial to mesenchymal phenotypic
      conversion of cells. These results, together with clinical findings point to the
      existence of an EGFR-independent role of cortactin in HNSCC that may have
      important implications regarding the design of targeted therapies to combat tumor
      spread.

PMID- 18607839
TI  - Life-threatening oxaliplatin-induced acute thrombocytopenia, hemolysis and
      bleeding: a case report.

PMID- 18607840
TI  - Real-time PCR quantification of human DKC1 expression in colorectal cancer.

PMID- 18607841
TI  - Retrospective analysis of surgical resection after induction chemotherapy for
      patients with T4b squamous cell head and neck cancer.
AB  - BACKGROUND: Standard treatment of patients with T4b squamous cell head and neck
      cancer (T4b-SCHNC) is concomitant chemo-radiotherapy (CT-RT). Recent Phase III
      trials with Taxane containing induction chemotherapy (IC) suggest that IC could
      also play a role in this setting. The value of resecting the residual mass after
      IC and before RT is not yet clear in this context. METHODS: We present the
      results of a retrospective analysis. RESULTS: Between 1984 and 2001, 113 patients
      (patients) with T4b-SCHNC were treated at our institution with IC. Four patients
      dead during IC and 57 patients achieved a complete or a >90% partial response at
      primary and proceeded to definitive RT (or concomitant CT/RT). Surgical resection
      was reconsidered after IC and before RT in the other 52 patients. Surgery was
      performed in 13 of them: in 7 patients resection was R1, all of them had loco
      regional progression (2 also developed systemic metastases) and median OS after
      surgery was 21 months, with no patient alive at 48 months. In the other 6
      patients a R0 resection was performed: 3 of these patients had loco-regional
      relapses (1 also developed systemic metastases) and the other 3 patients remain
      alive and disease free 56, 62 and 72 months after surgery. Considering the 52
      patients that achieved less than a 90% partial response at primary with IC,
      overall survival was equivalent when no Resection or an R1 resection was
      performed after IC (5 year OS 8 vs. 0%, lrk, p=0.74), but a statistically
      significant improvement in OS was observed when an R0 resection was obtained (5
      years OS 50%, lrk, p=0.02). CONCLUSIONS: R0 resections after IC and before RT
      could indicate an improvement in OS in patients with T4b-SCHNC that obtain less
      than a 90% PR at primary after IC. We consider that this approach deserves
      further research in prospective clinical trials.

PMID- 18607842
TI  - Acute aortic dissection in a hypertensive patient with prostate cancer undergoing
      chemotherapy containing bevacizumab.

PMID- 18607843
TI  - Radiofrequency ablation offers new treatment options in the elderly breast cancer
      patient.

PMID- 18607844
TI  - Chronic myelogenous leukemia exhibiting trisomy 14 due to a Robertsonian
      translocation with philadelphia chromosome.

PMID- 18607845
TI  - Carcinoma ex pleomorphic adenoma of the parotid gland. Study and implications for
      diagnostics and therapy.
AB  - BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is a rare parotid malignancy
      and until today no standardized concept exists for its therapy apart from
      recommendations for parotid carcinoma in general. Prognosis is thought to be
      poorer than for other parotid malignancies. We sought to describe a general
      diagnostic and therapy strategy and assess factors predicting the outcome.
      METHODS: We retrospectively analysed the courses of 22 patients with a CXPA of
      the parotid gland treated at a tertiary medical care centre for
      otorhinolaryngology. We examined parameters of medical history, diagnostics,
      surgical and adjunctive therapy and analysed overall and disease-specific
      survival. RESULTS: About half of the patients had evidence of a parotid mass of
      up to 1 year only while maximum of the others was 48 years. Nine patients were
      primarily operated without suspicion for malignancy. Both 5-year disease-specific
      and overall survival were 60%. Recurrence-free survival rate after 5 years was
      85%. Any patients with a stage I or II disease had an uneventful follow-up. To
      date, no patient with a stage IV disease has survived longer than 5 years.
      CONCLUSION: Surgical therapy (total or radical parotidectomy) is the method of
      choice for CXPA of the parotid gland. Stage I tumors have a very good and stage
      IV tumors a bad prognosis.

PMID- 18607846
TI  - High efficacy of pre-operative trastuzumab combined with paclitaxel following
      doxorubicin & cyclophosphamide in operable breast cancer.
AB  - BACKGROUND: Trastuzumab in combination with adjuvant chemotherapy improves
      disease free survival and overall survival in HER2 over-expressing breast cancer
      patients. Data concerning the use of trastuzumab in the neo-adjuvant setting is
      limited. We aimed to compare outcome of HER2 over-expressing breast cancer
      patients treated with either standard chemotherapy, consisting of doxorubicin,
      cyclophosphamide and a taxane to outcome of patients treated with the same
      chemotherapy regimen with the addition of trastuzumab in concurrence with
      paclitaxel. METHODS: We conducted a retrospective review of all consecutive HER2
      over-expressing breast cancer patients treated at the participating institutions
      during the study period and received neo-adjuvant therapy. Allocation to
      trastuzumab was not based on clinical parameters and was approved only by part of
      the insurers. Clinical and pathological characteristics, as well as response rate
      and type of surgery were analyzed. RESULTS: Thirty seven patients received
      chemotherapy alone and 24 patients received chemotherapy and trastuzumab. A
      similar distribution of age, clinical stage and histology was noted in both
      groups. The rate of pathological complete response (pCR) was significantly higher
      among the trastuzumab-treated group compared to chemotherapy-alone group (75 vs.
      24% respectively, p=0.0002). pCR in the breast was noted in 18 of 24 (75%)
      compared to 10 of 36 (28%, p=0.0005) and pCR in the axillary lymph nodes was
      noted in 19 of 20 (95%) compared to 8 of 28 (29%, p=0.0001), in the trastuzumab
      group compared to the chemotherapy-alone group respectively. The safety profile
      was similar between both groups and no clinical cardiotoxicity were noted.
      CONCLUSIONS: The addition of trastuzumab to standard chemotherapy in the neo
      adjuvant setting improves pathological complete response rates in HER2 over
      expressing breast cancer patients.

PMID- 18607847
TI  - Aberrant expression of cyclin E in low-risk node negative breast cancer.
AB  - BACKGROUND: Cyclin E is a cell cycle regulatory protein which occurs in G1, peaks
      in late G1 and is degraded in early S-phase. Cyclin E overexpression appears to
      be an independent prognostic factor for overall survival in breast cancer.
      Nuclear cyclin A is a reliable marker for S-and G2-phases. Consequently, aberrant
      expression of cyclin E can be detected by simultaneous immunostainings for cyclin
      A and cyclin E. Studies have shown that aberrant cyclin E might provide
      additional prognostic information compared to that of cyclin E alone. This study
      aimed to investigate cyclin E and aberrant cyclin E expression in low-risk node
      negative breast cancer. MATERIAL AND METHODS: We compared women that died from
      their breast cancer (n=17) with women free from relapse > 8 years after initial
      diagnosis (n=24). All women had stage I, low risk breast cancer. The groups were
      matched regarding tumour size, receptor status, adjuvant chemotherapy and tumour
      differentiation. Tumour samples were analysed regarding expression of cyclin A,
      cyclin E and double-stained tumour cells using immunoflourescence staining and
      digital microscopy. RESULTS: No differences were seen regarding expression of
      cyclin E or aberrant cyclin E in cases compared to controls. DISCUSSION: We
      conclude that neither cyclin E nor aberrant cyclin E is a prognostic factor in
      low-risk node negative breast cancer patients.

PMID- 18607848
TI  - Correlation of ultrasound findings with histology, tumor grade, and biological
      markers in breast cancer.
AB  - BACKGROUND AND PURPOSE: Ultrasound has been used successfully to differentiate
      benign and malignant breast lesions. The aim of this study was to investigate the
      correlation between ultrasound and prognostic indicators in breast cancer such as
      histological type, tumor grade, and biological markers. MATERIALS AND METHODS:
      Ultrasound findings (shape, margin, orientation, boundary, echo pattern,
      posterior acoustic feature, and presence of calcifications) of 458 breast cancers
      were analyzed and correlated with the tumor type, tumor grade, and biological
      markers by univariate and multivariate logistic regression analyses. The
      biological markers were estrogen receptor, progesterone receptor, and HER-2/neu.
      RESULTS: Invasive cancers displayed more frequently an irregular shape, a not
      parallel orientation, and a hypoechoic or complex echo pattern than carcinoma in
      situ cases (p < 0.05). Poorly differentiated invasive cancers had more frequently
      not circumscribed margins, an abrupt boundary, and a hypoechoic or complex echo
      pattern than moderately/well differentiated cancers (p < 0.05). Estrogen or
      progesterone receptor negative cancers more often displayed a hypoechoic or
      complex echo pattern and HER-2/neu positive cancers had more calcifications (p <
      0.05). CONCLUSION: Ultrasound pattern is correlated with tumor type, tumor grade,
      and biological markers in breast cancers and it may be useful for prediction of
      prognosis.

PMID- 18607849
TI  - Capecitabine-induced oromandibular dystonia: a case report and literature review.

PMID- 18607851
TI  - Somatic mutation of TRAF3 gene is rare in common human cancers and acute
      leukemias.

PMID- 18607850
TI  - Prognostic significance of numeric aberrations of genes for thymidylate synthase,
      thymidine phosphorylase and dihydrofolate reductase in colorectal cancer.
AB  - BACKGROUND: Most human cancer cells have structural aberrations of chromosomal
      regions leading to loss or gain of gene specific alleles. This study aimed to
      assess the range of gene copies per nucleus of thymidylate synthase (TYMS),
      thymidine phosphorylase (TP) and dihydrofolate reductase (DHFR) in colorectal
      cancer, and to evaluate its prognostic significance following adjuvant
      chemotherapy, since these enzymes are closely related to efficacy of 5
      fluorouracil (5FU). PATIENTS AND METHODS: Consecutive patients (n = 314), who
      were completely resected for colorectal cancer stages II-IV and adjuvantly
      treated with 5-FU were retrospectively evaluated. Paraffin embedded tumor
      specimens were assessed for gene copies per nucleus of TYMS, TP and DHFR by
      fluorescence in situ hybridisation (FISH) using specific peptide nucleic acid
      probes. Outcome according to gene copies per nucleus above and below the median
      were compared. Also TYMS expression, assessed by immunohistochemistry, was
      associated with TYMS copies per nucleus. RESULTS: The number of gene copies per
      nucleus were 1.7 (0.7-2.8), 1.8 (0.9-3.1) and 1.8 (1.1-2.7) median (range) for
      TYMS, TP and DHFR, respectively. TYMS expression was directly associated with
      TYMS genes per nucleus (p = 0.05). Cox multivariate analysis, adjusted for the
      prognostic impact of disease stage, vascular tumor invasion, and bowel
      obstruction at resection, revealed that high TYMS gene copy number was associated
      with significantly higher risk of recurrence (HR = 1.6; 95%CI 1.1-2.2; p = 0.02)
      and death (HR = 1.6; 95%CI 1.1-2.3; p = 0.01). No significant differences in
      outcome appeared according to TP and DHFR gene ratios. CONCLUSION: Aberration of
      TYMS gene is of significance to expression of TYMS, which may influence the
      biology and 5-FU sensitivity of colorectal cancer. This may be utilized in the
      allocation of patients for treatment approaches and for decision on follow-up
      programs.

PMID- 18607852
TI  - Expression of gamma-aminobutyric acid receptor (subtype A) in prostate cancer.
AB  - BACKGROUND: In prostate cancer, gamma-aminobutyric acid (GABA) has been
      previously reported to increase cellular proliferation via the ionotropic GABAa
      receptor (GABAar) and to promote cellular invasiveness via the metabotropic GABAb
      receptor. METHODS: In this study, we have investigated, by immunohistochemistry,
      GABAar levels in 12 normal human prostate, 13 benign prostatic hyperplasia (BPH)
      and 148 human prostate cancer specimens. We have also examined the effect of
      several GABA agonists and antagonists on the in vitro proliferation of four human
      prostate cancer cell lines: LNCaP, MDA-PCA-2b, DU145 and PC3. RESULTS: GABAar
      immunoreactivity was present in the stroma of ~75% of the normal and BPH
      specimens, and in 95% of the prostate cancer specimens. Also, low to moderate
      GABAar staining was observed in the acinar epithelium of 50 (33%) prostate cancer
      specimens. No correlation was observed between GABAar staining and patient age,
      Gleason Sum or TNM stage. A GABAa agonist isoguvacine, at doses between 5-50
      microg/ml (31-310 microM), stimulated the proliferation of all four human
      prostate cancer cell lines, tested. Baclofen, a GABAb agonist (up to 50
      microg/ml, 234 microM) had no effect on growth. Also, at concentrations up to 100
      microg/ml, GABA antagonists, bicuculline (223 microM), picrotoxin (166 microM)
      and saclofen (400 microM), did not have significant growth-inhibitory effects.
      However, dihydroergotoxine, which binds the GABAar chloride ion-channel,
      inhibited cellular proliferation (IC(50) 18-38 microM). CONCLUSIONS: These data
      indicate frequent expression of GABAar in prostate cancer and support a role for
      GABAar in the proliferation of prostate cancer cells.

PMID- 18607853
TI  - Radiation-induced sarcoma: 25-year experience from the Norwegian Radium Hospital.
AB  - BACKGROUND: The aim of this study was to determine the prevalence and outcome of
      radiation-induced sarcomas (RISs) among sarcoma patients referred to the
      Norwegian Radium Hospital (NRH). MATERIAL AND METHODS: Ninety patients were
      identified from the institutional sarcoma data base. Medical records and
      histological and cytological material from both primary and secondary tumours
      were reviewed. RESULTS: RIS represented 3.0 % of the sarcomas in the data base.
      The median latency time from radiotherapy of the primary tumour to the diagnosis
      of RIS was 13.6 years (range 2.5-57.8 years). Gynaecological, breast and
      testicular cancers were the most common primary diagnoses. For the RISs 13
      different histological types were identified including 25 malignant fibrous
      histiocytomas (28% of all) and 22 osteosarcomas (24%). The sarcoma-related 5-year
      crude survival was 33% (95 % CI 23-43 %). Unfavourable prognostic factors were
      metastases at presentation, incomplete surgery and presence of tumour necrosis.
      CONCLUSION: Radiation-induced sarcoma is rare and harbours an aggressive clinical
      behaviour. Complete surgical resection is mandatory for cure.

PMID- 18607854
TI  - Aggressive primary splenic CD5 positive/Cyclin D1 negative B-cell lymphoma in a
      patient with chronic hepatitis B virus infection.

PMID- 18607855
TI  - Weakness and numbness after chemotherapy for metastatic non-seminoma testis: a
      new neurological complication.

PMID- 18607857
TI  - Cost-effectiveness of maintenance rituximab treatment after second line therapy
      in patients with follicular lymphoma in Sweden.
AB  - INTRODUCTION: Rituximab has significantly improved the prognosis for patients
      with both indolent and aggressive non-Hodgkin's lymphoma. An economic evaluation
      was carried out to assess the cost-effectiveness in Sweden of rituximab as
      maintenance therapy for patients with follicular lymphoma in remission after
      second line therapy. MATERIALS AND METHODS: The incremental cost and
      effectiveness of rituximab maintenance therapy versus observation were evaluated
      in a health-state transition model. Primary effect measures were quality-adjusted
      life-years (QALY) and life-years gained (LYG). Model state transitions were
      calculated based on progression-free and overall survival data from the
      EORTC20981 trial. The analysis was made from the perspective of the healthcare
      provider, including direct medical costs presented in euro, 2007 value. Effects
      and costs were discounted at a 3% annual rate. The stability of the base case
      results were tested in one-way and probabilistic sensitivity analyses. RESULTS:
      The evaluation assessed rituximab maintenance therapy to be associated with an
      incremental cost per QALY gained of euro 12,600 and an incremental cost per LYG
      of euro 11,200. The average discounted life expectancy for patients on rituximab
      maintenance was 1.0 year longer than for patients on observation (5.96 vs. 4.94
      years). Rituximab maintenance was associated with an additional 0.9 QALY, and
      total costs per patient were euro 11,500 higher in the treatment arm, compared to
      observation. DISCUSSION: The results indicate that rituximab maintenance
      treatment after successful induction therapy for patients with
      relapsed/refractory follicular lymphoma in Sweden is cost-effective compared to
      observation.

PMID- 18607859
TI  - Stereotactic body radiotherapy of primary and metastatic renal lesions for
      patients with only one functioning kidney.
AB  - BACKGROUND: About 2% of patients with a carcinoma in one kidney develop either
      metastases or a new primary tumor in the contralateral kidney. Often, renal
      cancers progress rapidly at peripheral sites and a metastasis to the second
      kidney may not be the patient's main problem. However, when an initial renal
      cancer is more indolent yet spreads to the formerly unaffected kidney or a new
      primary tumor forms there, local treatment may be needed. Stereotactic body
      radiotherapy (SBRT) has been demonstrated as a valuable treatment option for
      tumors that cause local symptoms. Presented here is a retrospective analysis of
      patients in whom SBRT was used to control primary or metastatic renal disease.
      PATIENTS AND METHODS: Seven patients with a mean age of 64 (44-76) were treated
      for metastases from a malignant kidney to its contralateral counterpart.
      Dose/fractionation schedules varied between 10 Gy x 3 and 10 Gy x 4 depending on
      target location and size, given within one week. Follow-up times for patients who
      remained alive were 12, 52 and 66 months and for those who subsequently died were
      10, 16, 49 and 70 months. RESULTS: Local control, defined as radiologically
      stable disease or partial/complete response, was obtained in six of these seven
      patients and regained after retreatment in the one patient whose lesion
      progressed. Side effects were generally mild, and in five of the seven patients,
      kidney function remained unaffected after treatment. In two patients, the
      creatinine levels remained moderately elevated at approximately 160 micromol/L
      post treatment. At no time was dialysis required. CONCLUSION: These results
      indicate that SBRT is a valuable alternative to surgery and other options for
      patients with metastases from a cancer-bearing kidney to the remaining kidney and
      provides local tumor control with satisfactory kidney function.

PMID- 18607860
TI  - Selective internal radiation therapy in patients with carcinoid liver metastases.

PMID- 18607861
TI  - Primary ano-rectal malignant melanomas within a population-based national patient
      series in Sweden during 40 years.
AB  - PURPOSE: To analyze 251 patients (101 males and 150 females) diagnosed with ano
      rectal malignant melanoma (ARMM) reported to the Swedish National Cancer Registry
      during 1960-1999. METHODS: Incidence, gender and age profiles, primary anatomical
      sites and density of the melanomas along with geographic distribution, and
      prognosis were investigated. RESULTS: The age-standardized incidence of ARMM was
      significantly higher for females (1.0 per 10(6) females) than for males (0.7 per
      10(6) males) throughout the 40-year-period. The incidence increased with age
      peaking at 75-84 years in both genders. 54% of the tumours were primary in the
      anal canal, 24% engaged the whole ano-rectal unit and 10% were located at the
      anal verge (11% unknown primary site). Although ARMM were rare in absolute
      numbers, their density (number of tumours/square unit) was higher than that of
      cutaneous malignant melanomas (CMM) on average. No linkage between the geographic
      distribution of ARMM and population density was found. The prognosis was very
      poor albeit with a significant gender difference with a five-year survival rate
      of 10.6% for males and 15.7% for females. The survival rates for both genders
      improved during the 40-year-period but significantly more for females than males.
      CONCLUSION: The reason(s) for the difference in incidence and prognosis according
      to gender is unknown. The majority of ARMM emerged primary in the anal canal and
      a primary location exclusively in the colonic mucosa of the rectum is
      questionable. The higher density of ARMM as compared to the average density of
      CMM tallies with the result of our previous studies on vulvar melanoma and might
      be instrumental in exploring non-UV light associated factors in melanoma genesis.
      The concentration of patients with anal squamous cell carcinoma to population
      dense urban areas, as previously reported, was not found in cases of ARMM.

PMID- 18607862
TI  - Unsuccessful preoperative biopsies, fine needle aspiration cytology or core
      needle biopsy, lead to increased costs in the diagnostic workup in breast cancer.
AB  - Correct preoperative diagnosis of a breast lesion is essential for optimal
      treatment planning. Our aim was to compare feasibility of fine needle aspiration
      cytology (FNAC) and core needle biopsy (CNB) in diagnosis of breast lesions. The
      special aim was to evaluate the extra costs and delay in surgical treatment due
      to unsuccessful preoperative biopsies. Diagnostic work-ups in 572 patients with
      580 breast lesions were retrospectively evaluated. FNAC was the first biopsy
      method for 339 lesions, CNB for 241 lesions. The postoperative diagnosis was
      malignant for 503 lesions. The preoperative rate of definitely malignant
      diagnosis was 67% (194/289) for FNAC and 96% (206/214) for CNB (p < 0.0001), and
      95% and 99%, respectively (p = 0.0173), when also suspicious findings were
      included. In patients with FNAC, an additional needle biopsy was performed for 93
      and a surgical biopsy for 62 lesions. In the CNB group, a subsequent CNB was
      performed for 2 and a surgical biopsy for 33. The frequent need for additional
      biopsies raised the total expenses of FNAC over those of CNB. Multiple biopsies
      may also delay cancer surgery. It is therefore recommended to use CNB as the
      initial needle biopsy method.

PMID- 18607863
TI  - Dose intensity comparison between weekly and 3-weekly Cisplatin delivered
      concurrently with radical radiotherapy for head and neck cancer: a retrospective
      comparison from New Cross Hospital, Wolverhampton, UK.
AB  - AIMS: In this retrospective comparison, we describe the differences in dose
      intensity, delays and toxicity between weekly Cisplatin and 3-weekly Cisplatin
      given concurrently to patients with locally advanced squamous head and neck
      cancer (SCCHN) at New Cross Hospital, Wolverhampton. MATERIALS AND METHODS: Fifty
      one patients received radical Cisplatin based chemoradiotherapy for stage 4a
      SCCHN of the head and neck between September 2000 and December 2004. Twenty-seven
      patients were treated with 3-weekly inpatient Cisplatin for 3 cycles (20 patients
      80 mg/m(2); 7 patients-100 mg/m(2)) concomitantly with radiotherapy (66-70 Gy/33
      35 fractions). Twenty-four patients received a similar radiotherapy schedule but
      received weekly Cisplatin 33-40 mg/m(2). RESULTS: More patients received a higher
      cumulative dose of at least 240 mg/m(2) if given weekly Cisplatin 40 mg/m(2) or 3
      weekly Cisplatin 80 mg/m(2) compared with those receiving Cisplatin 3-weekly 100
      mg/m(2) (p=0.04). Maximum cumulative dose achievable in the latter group was only
      200 mg/m(2) and none achieved the full 3 cycles. Mean Cisplatin dose in the
      weekly Cisplatin 40 mg/m(2) regime (mean 202 mg/m(2)) and 3-weekly arm of 80
      mg/m(2) (mean 203 mg/m(2)) was higher than that reached if given 3-weekly
      Cisplatin 100 mg/m(2) (mean 180 mg/m(2)) although statistically insignificant
      (p=0.39) due to the small number of patients. More delays (29% vs. 41%) and
      omission of chemotherapy (5.6% vs. 17.4%) occurred in the 3-weekly compared with
      the weekly regime. Toxicity, radiotherapy overall treatment time and delays were
      similar between the two groups. CONCLUSION: Delivery of 100 mg/m(2) Cisplatin 3
      weekly with radiotherapy was less tolerated than 40 mg/m(2) weekly and resulted
      in less patients achieving cumulative dose beyond 200 mg/m(2), potentially
      lowering chemotherapy dose intensity.

PMID- 18607864
TI  - Pituitary Adenoma Neuronal CHoristoma -- The PANCH syndrome.

PMID- 18607865
TI  - Genetic and epigenetic analysis of the VHL gene in gastric cancers.
AB  - The von Hippel-Lindau tumor suppressor gene (VHL), which is located on chromosome
      3p25, plays an important role in tumorigenesis, particularly in tumor growth and
      vascularization. Mutations of the VHL gene have been observed in the hereditary
      VHL syndrome and a variety of other sporadic cancers. In this study, in order to
      investigate whether the VHL gene is involved in gastric carcinogenesis, we have
      examined the genetic alterations, including somatic mutations and allelic loss,
      with the two microsatellite markers, D3S1038 and D3S1110, as well as promoter
      hypermethylation of the VHL gene in 88 sporadic gastric adenocarcinomas. No
      mutation was detected in the coding region of the VHL gene. Allelic loss was
      found in 20 (33.9%) of 59 informative cancer cases at one or both markers. In
      addition, promoter hypermethylation was not detected in the gastric cancer
      samples. This is the first investigation of the genetic and epigenetic
      alterations of the VHL gene in gastric cancers. Our results suggest that genetic
      and epigenetic alterations of the VHL gene may be not involved in the development
      or progression of gastric cancers. The findings also provide evidence for the
      presence of another gastric cancer specific tumor suppressor gene at the 3p25
      region.

PMID- 18607866
TI  - Predicting distant dissemination in patients with early breast cancer.
AB  - BACKGROUND: Prediction of distant metastases is of paramount importance in the
      knowledge and management of breast cancer patients. The objective of this study
      was to assess conventional prognostic factors in a large database of patients
      with early breast cancer, including those with small tumors diagnosed through
      regional screening, to determine the risk of distant dissemination. METHODS: The
      study included 4,797 patients of the Stockholm database who did not receive
      systemic adjuvant treatments. The main endpoint was metastasis free-interval.
      Individual risks of distant metastasis were estimated using the regression
      coefficients of the significant prognostic factors in Cox multivariate analyses.
      For each level of metastatic risk the pattern of failure was analyzed by a model
      assuming competing risks. RESULTS: The three independent significant prognostic
      factors were histologic tumor size, number of involved axillary lymph nodes and
      progesterone receptor level. However, the latter factor added limited additional
      information of borderline clinical significance. Thus, subsequent estimations
      were done with a prognostic score taking into account only the former two most
      performant factors in the whole population. The risk of distant metastasis of
      observed values of tumor size categories fitted with published results of a
      series containing significantly larger tumors. A large variation of tumor size
      predicts 10-year distant metastasis risk ranging from below 10% up to 90%. Tumors
      of 10 mm or less had a 10-year metastatic risk of less than 10%. CONCLUSIONS: The
      results of this study are consistent with a linear effect of tumor size, within
      the range of data, on 10-year distant dissemination probabilities. Further
      refinement on prognostic value is needed for tumors of 15 mm or less.

PMID- 18607867
TI  - Validation of smoking history in cancer patients.
AB  - OBJECTIVE: The aim of the study was to investigate the agreement between patient
      records and the information reported from relatives, and how the relationship and
      time since patient's death affected the response rate and the quality of the
      data. METHODS: A questionnaire regarding smoking history was sent to next-of-kin
      of 270 deceased women diagnosed with breast cancer during 1958-2000 in the
      Stockholm County. Agreement between the reports of next-of-kin and patient
      records was calculated using a kappa statistics, along with its 95% confidence
      interval. RESULTS: When information about overall smoking history from patient
      records and next-of-kin was compared, the kappa value was 0.83 (95% confidence
      interval (CI): 0.73-0.92). Using two smoking categories (<or=15 cigarettes,>15
      cigarettes), for quantitative smoking history the kappa value was 0.46. No
      evidence of a trend toward under-/over-reporting among next-of-kin was found. The
      overall smoking agreement between medical record and next-of-kin was similar for
      the two median recall periods (<or=10 years and >10 years), with kappa value 0.80
      and 0.83, respectively. CONCLUSION: Next-of-kin can provide reliable information
      with almost perfect agreement with patient records on lifetime smoking status,
      and should be considered in studies where information on smoking history is
      missing.

PMID- 18607868
TI  - Local excision for more advanced rectal tumors.
AB  - Over the past 20 years, local excision (LE) of T1 rectal cancer was increasingly
      established and represents an oncologically established technique. In contrast,
      the situation for T2 tumors is less clear and has only been investigated in small
      patient collectives. LE for T2 tumors is thus discussed controversially.
      MATERIALS AND METHODS: In addition to our own patients with T2 rectal cancer
      treated locally (n=40), we have analysed the local recurrence (LR) rates after LE
      alone (n=124), after immediate conventional radical reoperation (n=29), after
      adjuvant (chemo)-radiotherapy (n=294) and those after neoadjuvant
      chemoradiotherapy (nCRT) (n=269) using a PubMed search. RESULTS: LR rates of low
      grade T2 tumors after R0 resection by LE alone was 19%. If additional
      prognostically unfavorable findings were present, the LR rate rose to 52%. By
      immediate radical reoperation the LR rate was decreased to 7%, whereas that after
      adjuvant therapy was 16%. In contrast, LE of more advanced tumors after nCRT
      resulted in LR rates of 9%. DISCUSSION: LE alone of T2 rectal cancer should not
      be performed, and after adjuvant chemoradiotherapy the risk of developing LR was
      also high. In cases with unexpected T2 finding after LE, immediate conventional
      reoperation can represent an adequate oncological therapy, because it reveals
      comparable results to those obtained by primary radical resection. First results
      after nCRT followed by LE showed favorable results with low LR rates. If the
      indication for LE of T2 cancers can be extended to patients after nCRT in the
      future will have to be determined in prospective mutlticentre studies.

PMID- 18607869
TI  - Clear cell sarcoma originating in a paraspinous tendon: case report and
      literature review.

PMID- 18607870
TI  - Management of severe infusion reactions after cetuximab.

PMID- 18607871
TI  - Fracture risk in patients with different types of cancer.
AB  - BACKGROUND: Few studies on the risk of fractures in patients with cancer exist,
      and little is known on the mechanisms of fractures in patients with cancer. We
      studied the risk of fracture in patients with various types of cancer. SUBJECTS
      AND METHODS: Case control study. There were 124,655 fracture cases and 373,962
      age and gender matched controls. RESULTS: An increased risk of fractures,
      primarily within the first year after diagnosis was seen in patients with primary
      bone cancer (OR=3.51, 95% CI: 1.54-8.01), multiple myeloma (OR=5.21, 95% CI: 2.96
      9.19), metastases to the bone (OR=5.28, 95% CI: 3.58-7.79), metastases to other
      organs than bone (OR=1.85, 95% CI: 1.50-2.29), lung cancer (OR=1.90, 95% CI: 1.51
      2.38), and cancer of the liver, gall bladder and pancreas (2.14, 95% CI: 1.39
      3.31). For patients with prostate cancer an increase in the risk of fractures was
      seen with time. Other cancer types were not associated with an increased risk of
      fractures. CONCLUSIONS: A high risk group regarding fractures includes cancers
      primarily affecting the bone (primary bone cancer, multiple myeloma, metastases
      to the bone, metastases to other organs than bone, lung cancer, and cancer of the
      liver, gall bladder and pancreas, and prostate cancer). The main increase in risk
      of fractures in this group was seen within the first year following diagnosis. A
      low risk group for fractures included all other cancer types (e.g. cancer of the
      breast, colon, skin etc). This may have implication for which patients should be
      selected for prevention against fractures.

PMID- 18607872
TI  - Docetaxel and carboplatin combination chemotherapy as outpatient palliative
      therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative
      Oncology Group phase II study.
AB  - INTRODUCTION: Taxane/platinum combinations exhibit synergistic cytotoxicity and
      activity against a broad range of solid tumours. We sought to optimise the
      regimen as a suitable outpatient palliative treatment for cancer of unknown
      primary (CUP). PATIENTS AND METHODS: Eligible CUP patients with adenocarcinoma or
      poorly differentiated carcinoma, performance status of 0-2, adequate organ
      function and assessable disease were treated with docetaxel 75 mg/m(2) and
      carboplatin at an area under the concentration time-curve (AUC) of 5, both as 30
      minute intravenous infusions, every three weeks. Patients with isolated axillary
      adenopathy, squamous cell cervical or inguinal adenopathy and PSA or germ-cell
      serum tumour markers were excluded. RESULTS: Forty-seven patients entered the
      trial, 24 with predominantly nodal disease or non-mucinous peritoneal
      carcinomatosis (favourable risk) and 23 with visceral metastases (unfavourable
      risk). A median of 6 cycles of chemotherapy were administered, with relative dose
      intensities of both drugs >90%. Response rates were 32% (46% in favourable risk,
      17% in unfavourable), comparable to the activity of paclitaxel/platinum regimes,
      though complete remissions were seen only in favourable risk patients.
      Granulocyte-colony stimulating factor support was used in a third of treatment
      cycles. Toxicity was mild and manageable, with grade 3-4 neutropenia in 26% of
      patients, febrile neutropenia in 7% and severe non-hematologic side-effects in
      less than 8% of patients. No toxic deaths or severe neurotoxicity were seen.
      Median time to progression (TTP) and overall survival (OS) were 5.5 and 16.2
      months respectively. Survival was driven mainly by favourable-risk patients (22.6
      months), as those with visceral metastases had a poor median survival of only 5.3
      months. Good performance status and low-volume disease predicted for superior
      outcome, while docetaxel relative dose-intensity was a positive prognosticator
      only in favourable-risk patients. CONCLUSIONS: One-hour docetaxel/carboplatin is
      a convenient, safe and effective outpatient palliative treatment for CUP
      patients, providing meaningful survival prolongation only in favourable-risk
      patients. Insights in the molecular biology of CUP are needed for the development
      of targeted therapeutic manipulations of malignant resistance and progression.

PMID- 18607873
TI  - Cancer survival analysis in Hamburg 1995-2003: assessing the data quality within
      a population-based registry.
AB  - INTRODUCTION: Population-based cancer survival analysis constitutes valuable
      reference material for the clinical field of oncology. The objectives of this
      study were to assess the quality of the Hamburg Cancer Registry's (HCR) database
      in this respect, to perform survival analyses by means of selected sites, and to
      evaluate the results in relation to prevalent opinions and external estimates.
      METHODS: Data quality was assessed by the proportion of cases documented as
      diagnosed at death, external estimates of completeness, reliability of follow-up,
      histological verification and information on stage. Included were first primary
      malignancies of the colon (ICD10 C18, n=4,544), female breast (C50, n=9,259),
      prostate (C61, n=5,707) and urinary bladder (C67, D09.0, n=3,148), diagnosed in
      Hamburg residents 1995-2003. Observed and relative survival (OS, RS) were
      estimated by site, sex, time, age and stage. RESULTS: Regarding female breast
      cancer in Hamburg, high levels of data quality and completeness exist while the
      explanatory power concerning malignancies of the colon, prostate and urinary
      bladder is limited. Age-standardised 5-year relative cancer survival estimates
      amounted for female breast to 81%, for colon to 49% (male) and 52% (female), for
      prostate to 81% and for urinary bladder to 71% (male) and 62% (female).
      CONCLUSION: The study demonstrates the capacities and limitations of an
      epidemiological cancer registry to produce convincing survival estimates for
      clinical use, under the terms of a voluntary case reporting system.

PMID- 18607874
TI  - Long-term mortality in a cohort study of 6,800 French breast cancer patients
      treated between 1954 and 1983.
AB  - PURPOSE: To investigate the impact of initial tumour characteristics and loco
      regional radiotherapy on long-term survival following breast cancer diagnosis.
      METHODS AND MATERIALS: This study was conducted among 6,800 French women from a
      cohort of 7 711 subjects diagnosed at the IGR with breast cancer between 1954 and
      1983 and followed-up until January 2004. Overall mortality in the cohort was
      compared with that in the French general population using Standardized Mortality
      Ratios (SMR) and the Absolute Excess Risk (AER) estimated by Poisson regression.
      RESULTS: During the 1954-2004 follow-up period, 5,436 women died. Mortality was
      3.15-fold higher in the cohort than in the general female population in France.
      It decreased from 6.86 to 1.26 during the first 30 years of follow-up then rose
      again to 1.60. Both SMRs and AERs were more than 2-fold higher in women who had
      received radiotherapy during initial treatment than in those who had not, this
      difference being higher for women treated before 1976 than afterwards (p <
      0.0001). They (SMRs and AERs) were also higher for subjects who had stage II, III
      or IV lesions than for those with less advanced tumours. CONCLUSION: The results
      of this study suggest that the excess deaths observed during the first two
      decades are closely linked to the initial clinical characteristics of the tumour
      and to radiotherapy. The late increase in mortality may be partially due to
      deleterious late effects of radiotherapy.

PMID- 18607875
TI  - Bowel dysfunction after treatment for rectal cancer.
AB  - INTRODUCTION: Rectal cancer is a common disease in Western populations. Improved
      treatment modalities have resulted in increased survival and tumour control. With
      increasing survival there is a growing need for knowledge about the long-term
      side effects and functional results after the treatment. AIM: To describe the
      long-term functional outcome in patients treated for rectal cancer through a
      systematic review of the current literature and to provide an outline of the
      promising developments within this area. RESULTS: Standard resectional surgery
      with loss of the rectal reservoir function results in poor functional results in
      up to 50-60% of the patients. New methods of surgery including the construction
      of a neoreservoir and improvement of the technique for local excision have been
      developed to minimize the functional disturbances without compromising the
      oncological result. The addition of chemo and/or radiotherapy approximately
      doubles the risk of poor functional results. During the last decades the
      techniques for chemo/radiotherapy has been markedly improved with a positive
      impact on functional outcome. New methods for treatment of functional
      disturbances e.g. bowel irrigation and sacral nerve stimulation are currently
      under development. PERSPECTIVES: To improve the functional outcome in this
      growing patient population several approaches can be taken. The primary cancer
      treatment must be improved by minimizing the surgical trauma and optimizing the
      imaging and radiation techniques. Population screening should be considered in
      order to find the cancers at an earlier stage, hereby increasing the proportion
      of patients eligible for local excision without the need for chemo/irradiation.
      All patients recovering from rectal resection should be examined and registered
      systematically regarding their functional results and treatment should be offered
      to the severely affected patients. More studies are still needed to evaluate the
      efficacy of irrigation and nerve stimulation in this patient group.

PMID- 18607876
TI  - A phase II study of thalidomide in patients with brain metastases from malignant
      melanoma.
AB  - INTRODUCTION: Brain metastases develop in nearly half of the patients with
      advanced melanoma and in 15 to 20% of these patients CNS is the first site of
      relapse. Overall median survival is short, ranging from 2 to 4 months.
      Thalidomide has antiangiogenic and immunomodulatory effects. Results obtained in
      prior trials indicate that Thalidomide acts as a cytostatic agent in metastatic
      melanoma. We evaluated single agent antitumour activity and toxicity of
      Thalidomide in a phase II setting in patients with brain metastases associated
      with metastatic melanoma. MATERIAL AND METHODS: Patients with measurable
      metastatic melanoma in progression and with PS < or = 2 were enrolled in the
      study. Thalidomide was given orally. Dose was escalated over 4 weeks from 100
      mg/day to 400 mg/day. Primary objective of the study was to determine response
      rate, according to RECIST. Secondary objectives were to estimate time to
      progression, overall survival and to evaluate tolerability of the regimen.
      RESULTS: Twenty five men and 11 women were enrolled in the study, median age 48
      years. Among 36 eligible patients 35 were evaluable for response. None of the
      patients obtained a response in brain metastases. Three patients obtained a
      partial response in extracranial lesions. Toxicity was acceptable and manageably.
      Median time to progression and overall survival time was 1.7 and 3.1 months,
      respectively. CONCLUSION: There were no objective responses in the brain but
      single agent Thalidomide has some activity in melanoma patients with brain
      metastases. It has encouraged us to investigate Thalidomide in combination with
      Temozolomide, a very lipophilic agent, in this group of patients.

PMID- 18607877
TI  - Morphology, metabolism, microcirculation, and strength of skeletal muscles in
      cancer-related cachexia.
AB  - PURPOSE: Cancer-related cachexia is an obscure syndrome leading to muscle
      wasting, reduced physical fitness and quality of life. The aim of this study was
      to assess morphology, metabolism, and microcirculation in skeletal muscles of
      patients with cancer-related cachexia and to compare these data with matched
      healthy volunteers. METHODS: In 19 patients with cancer-induced cachexia and 19
      age-, gender-, and body-height-matched healthy volunteers body composition and
      aerobic capacity (VO(2max)) were analyzed. Skeletal muscle fiber size and
      capillarization were evaluated in biopsies of the vastus lateralis muscle. The
      cross-sectional area (CSA) of the quadriceps femoris muscle was measured by
      magnetic resonance imaging as well as its isokinetic and isometric force. The
      energy and lipid metabolism of the vastus lateralis muscle was quantified by
      (31)P and (1)H spectroscopy and parameters of its microcirculation by contrast
      enhanced ultrasonography (CEUS). RESULTS: Morphologic parameters were about 30%
      lower in cachexia than in volunteers (body mass index: 20 +/- 3 vs. 27 +/- 4 kg
      m(-2), CSA: 45 +/- 13 vs. 67 +/- 14 cm(2), total fiber size: 2854 +/- 1112 vs.
      4181 +/- 1461 microm(2)). VO(2max) was reduced in cachexia (23 +/- 9 vs. 32 +/- 7
      ml min(-1) kg(-1), p=0.03), whereas histologically determined capillary density
      and microcirculation in vivo were not different. Both concentrations of muscular
      energy metabolites, pH, and trimethyl-ammonium-containing compounds were
      comparable in both groups. Absolute strength of quadriceps muscle was reduced in
      cachexia (isometric: 107 +/- 40 vs. 160 +/- 40 Nm, isokinetic: 101 +/- 46 vs. 167
      +/- 50 Nm; p=0.03), but identical when normalized on CSA (isometric: 2.4 +/- 0.5
      vs. 2.4 +/- 0.4 Nm cm(-2), isokinetic: 2.2 +/- 0.4 vs. 2.5 +/- 0.5 Nm cm(-2)).
      CONCLUSIONS: Cancer-related cachexia is associated with a loss of muscle volume
      but not of functionality, which can be a rationale for muscle training.

PMID- 18607878
TI  - The radiosensitivity of total and quiescent cell populations in solid tumors to
      290 MeV/u carbon ion beam irradiation in vivo.
AB  - PURPOSE: To clarify the radiosensitivity of intratumor total and quiescent (Q)
      cells in vivo to accelerated carbon ion beams compared with gamma-ray
      irradiation. MATERIALS AND METHODS: SCC VII tumor-bearing mice received a
      continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all
      intratumor proliferating (P) cells. Then they received 290 MeV/u carbon ions or
      gamma-rays. Immediately or 12 hours after the irradiation, the radiosensitivity
      of Q cells was assessed in terms of the micronucleus frequency using
      immunofluorescence staining for BrdU. That of the total (=P+Q) tumor cells was
      determined from the BrdU non-treated tumors based on the micronucleus frequency
      and clonogenic cell survival. RESULTS: The apparent difference in
      radiosensitivity between total and Q cell populations under gamma-ray irradiation
      was markedly reduced with carbon ion beam, especially with a higher linear energy
      transfer (LET) value. Clearer repair in Q cells than total cells through delayed
      assay under gamma-ray irradiation was efficiently inhibited with carbon ion
      beams, especially with a higher LET. CONCLUSION: In terms of tumor cell-killing
      effect as a whole, including intratumor Q cells, carbon ion beams, especially
      with higher LET values, were very useful for suppressing the dependency on the
      heterogeneity within solid tumors as well as depositing radiation dose precisely.

PMID- 18607879
TI  - Radiotherapy for Peyronie's Disease: a European survey.
AB  - BACKGROUND AND PURPOSE: Peyronie's Disease (PD) is a benign condition
      characterized by penile nodules, pain and curvature. Radiotherapy has been used
      for many years with positive outcomes, however all studies published were non
      randomized or non-controlled. The purpose of this survey was to understand which
      treatment policy is followed in Europe before setting up a randomized trial.
      MATERIALS AND METHODS: A questionnaire was sent out to 908 European radiotherapy
      institutions, 402 questionnaires were sent back and filled out correctly (44.5%).
      The questionnaire consisted of different items, regarding number of patients
      referred, fraction dose, total dose and technique used, and eventually treatment
      outcome of clinical trials. RESULTS: Seventy-three institutions irradiate PD
      (19%), 304 do not (81%). Reasons for not treating were insufficient referrals
      from urologists or no interest in treating benign diseases. The most common
      fraction dose is 2 (range 0.5-8) Gy and the total radiation dose 20 (range 3-30)
      Gy. Most of the institutions use electrons (n = 44) or orthovoltage (n = 32).
      Decreased pain is reported in about 80% of the cases, and side effects by eight
      institutions. CONCLUSIONS: So far, a large variation of treatment schedules for
      radiotherapy of PD has been detected in European countries. Although the results
      are good and side effects minimal, there is still a need to set up a European
      randomized trial to prospectively evaluate the efficacy of radiotherapy for PD.

PMID- 18607880
TI  - Survival in ovarian cancer patients by histology and family history.
AB  - INTRODUCTION: Earlier studies suggest that histology has no prognostic
      significance in patients with invasive ovarian tumors. Studies about the effect
      of family history on survival have given conflicting results, which we try to
      clarify in this study. As an additional question, we examined whether family
      members share survival experience. METHODS: We used the nation-wide Swedish
      Family-Cancer Database to estimate hazard ratios (HRs) for cause-specific and
      overall survival in ovarian cancer patients by histology and family history. HRs
      show the probability of death in the study group compared to the reference group.
      RESULTS: A total of 6,049 ovarian cancer patients with specific histologies were
      retrieved from our Database from years 1993 to 1999. Compared to women with
      epithelial ovarian cancer, women with borderline epithelial tumors had the best
      survival (HR 0.02 and 0.14 for cause-specific and overall survival). Good
      survival was also noted for patients with sex cord-stromal tumors and germ cell
      tumors. Among specific subtypes of epithelial ovarian cancers, good survival was
      noted for women with clear cell and endometrioid carcinomas and mucinous
      cystadenocarcinoma. The study covered 80 mother-daughter pairs with a family
      history. Patients with a family history had a poorer survival than sporadic cases
      in both maternal and offspring generations. When the survival was analyzed
      according to the probands' length of survival, there was a non-significant
      concordance of prognosis. CONCLUSION: Our data showed that histology and family
      history are prognostic factors for ovarian tumors. Patients with a family history
      had a more aggressive course than the sporadic cases.

PMID- 18607881
TI  - Cost-effectiveness of HER2 testing and trastuzumab therapy for metastatic breast
      cancer.
AB  - BACKGROUND: Trastuzumab is a monoclonal antibody that together with chemotherapy
      significantly improves time to progression and overall survival for metastatic
      breast cancer patients with tumours overexpressing HER2. The aim of this study
      was to analyse the cost-effectiveness of HER2 testing and trastuzumab in
      combination with chemotherapy compared with chemotherapy alone from a societal
      perspective in a Swedish setting. MATERIAL AND METHODS: We used a Markov state
      transition model to simulate HER2 testing and subsequent treatment in a
      hypothetical cohort of 65 year old metastatic breast cancer patients. Outcomes
      included life-time costs, quality adjusted life years (QALY), and cost per QALY
      gained. Five different testing and treatment strategies were evaluated. RESULTS:
      We estimated the cost per QALY gained to be about 485,000 SEK for the strategy of
      IHC testing for all patients, with FISH confirmation of 2+ and 3+, and
      trastuzumab and chemotherapy treatment for FISH positive patients. For the
      strategy of FISH testing for all patients, with trastuzumab and chemotherapy for
      FISH positive patients, we estimated the cost per QALY gained to about 561,000
      SEK. The remaining testing and treatment strategies were dominated. Results were
      sensitive to changes in utilities, the risk of breast cancer related death, and
      test characteristics. CONCLUSION: Our analysis indicate that FISH testing for all
      patients with trastuzumab and chemotherapy treatment for FISH positive patients
      is a cost-effective treatment option from a societal perspective.

PMID- 18607882
TI  - Intravenous administration of CP-4055 (ELACYT) in patients with solid tumours. A
      Phase I study.
AB  - PURPOSE: Cytarabine (ara-C) has limited activity in solid tumours. CP-4055
      (ELACYT) is a novel ara-C-5'-elaidic acid ester that may circumvent this
      limitation. CP-4055 maximum tolerated dose (MTD), pharmacokinetics and antitumor
      activity have been investigated in patients with solid tumours. MATERIAL AND
      METHODS: Thirty-four patients (19 malignant melanoma, 8 ovarian cancers and 7
      NSCLC) received CP-4055 as a 30 min, or 2 hr intravenous (IV) infusion daily for
      5 consecutive days every 3 or 4 weeks (D1-5 q3w or D1-5 q4w) in a dose escalation
      designed study with doses ranging from 30 to 240 mg/m(2)/day. RESULTS: The most
      frequent CTC grade 1-2 adverse events (AEs) were nausea, fatigue, vomiting,
      anorexia and pyrexia. Most of the grade 3-4 AEs were neutropenia. The MTD was 200
      mg/m(2)/day and 240 mg/m(2)/day for D1-5 q3w and D1-5 q4w, respectively. The MTD
      was independent of infusion time in the 4 week schedule. CP-4055 was maintained
      in plasma for up to 5-10 hr at dose levels >150 mg/m(2)/day. One objective
      partial response (PR) with time to progression (TTP) of 22 months was reported in
      an advanced malignant melanoma patient. CONCLUSION: CP-4055 was well tolerated;
      the majority of the AEs were of CTC grade 1. The 3 week schedule was not
      recommended due to neutropenic nadir between days 18-26. The recommended dose was
      200 mg/m(2)/day in a D1-5 q4w schedule. Efficacy data suggest that CP-4055 might
      be active in treatment of solid tumours.

PMID- 18607883
TI  - Cellular senescence in oral cancer and precancer and treatment implications: a
      review.
AB  - INTRODUCTION: Recent studies have demonstrated the capacity of the human organism
      to prevent the growth of potentially carcinogenic cells by paralyzing them. This
      antitumor mechanism is known as cellular senescence and is defined as an
      emergency defence system for cells on the way to becoming cancerous. RESULTS:
      This review of the literature suggests that oncogene-induced senescence may be a
      response to oncogenic activation, acting as a natural barrier against
      tumorigenesis at a premalignant stage. Thus, a large number of cells enter
      senescence in premalignant lesions but none do so in malignant tumors, due to the
      loss of senescent pathway effectors such as p16(INK4a) or ARF-p53. Potential
      senescence markers in oral precancerous lesions include p21(WAF1), p16(INK4a),
      pRb, Maspin, RAR-beta, G-actin, p15(INK4b), DCR2, and DEC1, some of which are
      currently under study. CONCLUSION: In the short term, the study of this mechanism
      may yield valuable data for the management of oral cancer and precancer, for
      which no effective diagnostic or prognostic markers are yet available.

PMID- 18607885
TI  - Hepatocellular carcinoma developing years after extended field radiation for
      Hodgkin's lymphoma.

PMID- 18607884
TI  - Developing and testing an instrument for identifying culture-specific barriers to
      breast cancer screening in Israeli Arab women.
AB  - AIMS: To develop and assess an instrument for studying culture-specific barriers
      to performing examinations for early detection of breast cancer. METHODS: A three
      step design: (a) content analysis of five focus groups (n=51); (b) constructing
      and initial testing of the Arab culture-specific barriers (ACSB) instrument in a
      pilot study (n=79); (c) testing for validity and reliability of the revised ACSB
      instrument (n=300, of these 200 Muslim and 100 Christian, mean age 48). Construct
      validity was examined using factor analysis. Performance of screenings
      (mammography and clinical and self breast examination) was used to test criterion
      validity by logistic regression and receiver operating characteristic (ROC)
      curve; convergent validity was tested by the barriers subscale of the health
      beliefs questionnaire. Internal consistency reliability was tested by Cronbach's
      alpha coefficients. RESULTS: Factor analysis revealed five subscales: social
      barriers, exposure barriers, environmental barriers, uneasiness with own body,
      and traditional beliefs concerning cancer. The factors accounted for 54.6% of
      cumulative variance. Twelve items not meeting item-scale criteria were removed,
      resulting in a 21-item instrument. Convergent validity was confirmed for all
      subscales except traditional beliefs. ACSB mean score explained between 0.79 (95%
      CI .72-.86) and 0.85 (95% CI .79-.94) of the area under the ROC curve of the
      screening procedures. Internal consistency of the subscales ranged from 0.76 to
      0.90. CONCLUSIONS: The study showed initial satisfactory reliability of the ACSB.
      Validity was approved for social barriers, exposure barriers, environmental
      barriers and uneasiness with own body subscales, and only partially for
      traditional beliefs. Further examination of the instrument with different
      populations of Arab women is needed.

PMID- 18607886
TI  - Superantigens and the expression of T-cell receptor repertoire in chronic
      rhinosinusitis with nasal polyps.
AB  - CONCLUSIONS: Staphylococcal exotoxins (SEs), acting as superantigens, activate
      the beta variable chains of T-cell receptors (TCRVbeta) with subsequent massive
      proliferation and corresponding excursion of gene spectra, thereby contributing
      to the etiology of chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVES:
      To demonstrate the presence of SEs in sinonasal mucosa, and determine the effect
      of superantigens on the T cells expressing the target of superantigen, i.e.
      TCRVbeta in patients with CRSwNP. MATERIALS AND METHODS: Nasal mucosa and
      sinonasal polyp tissue specimens were obtained from 37 patients with CRS (22 with
      bilateral nasal polyps, 15 without nasal polyps). Specimens were assayed by
      enzyme-linked immunosorbent assay (ELISA) for SEs (SEA, SEB, SEC, SED) and toxic
      shock syndrome toxin type-1 (TSST-1), and analyzed by flow cytometry and reverse
      transcriptase-polymerase chain reaction (RT-PCR), respectively, to determine the
      expression of TCRVbeta repertoire. RESULTS: In the CRSwNP subjects 12 of 22
      samples (54.54%) demonstrated reactivity for staphylococcal exotoxins. There was
      no positive result in the CRS without nasal polyps or normal control group. There
      was a high percentage of Vbeta+ T cells in the superantigen-positive group. The
      expressional intensity of Vbeta3, 14, 15, 17, and 20 was specifically enhanced in
      SEB-positive subjects, as well as that of Vbeta2 and 6.1-3 in specimens that were
      TSST-1-positive compared with those that were negative for superantigens (all
      p<0.05). There were no dominantly expressed Vbeta fragments in ELISA-negative
      specimens.

PMID- 18607887
TI  - External vs endoscopic approach for inverted papilloma of the sino-nasal
      cavities: a retrospective study of 136 cases.
AB  - CONCLUSION: Endoscopic removal, with or without external technique, can be
      performed in a majority of inverted papilloma cases. This method has subsequent
      recurrence rates that are comparable to those of more aggressive external
      techniques and it is more cost efficient with less morbidity. OBJECTIVES: To
      analyze the clinical outcomes of our 21-year experience (1986-2006) in treating
      inverted papillomas using different treatment modalities. PATIENTS AND METHODS:
      The patients were divided into a conventional surgery group (CSG) and an
      endoscopic surgery group (ESG) and were staged according to the system developed
      by Krouse. A retrospective assessment was performed. RESULTS: The recurrence
      rates were 4.3% in ESG and 9.5% in CSG. There was no significant difference in
      the recurrence rates according to the treatment modality used and the Krouse
      stage in the two groups. Mean operation time was 72.93+/-18.51 min in the ESG and
      112.02+/-56.52 min in the CSG. Mean period of hospital stay was 4.66+/-1.75 days
      in the ESG and 9.54+/-4.79 days in the CSG. The complication rate was 3.2% in the
      ESG and 33.3% in the CSG. There was a significant difference in the operation
      time, length of hospital stay, and complication rate in the two groups.

PMID- 18607888
TI  - Comparative study on the morphology and the composition of the otoliths in the
      teleosts.
AB  - CONCLUSION: Saccular otoliths of teleosts were mostly larger than utricular
      otoliths, which might relate to the three-dimensional movement. The large and
      heavy otolith may be better suited in saccules of the bottom and reef fishes. The
      quantities of iron in lagenar otoliths were found to be lower than those of
      birds. The function of the fish lagena remains to be elucidated by further
      studies. OBJECTIVE: To evaluate the morphological characteristics and the
      chemical composition of the otoliths in fishes as related to behaviour and
      habitat. MATERIALS AND METHODS: We studied the morphology of the otoliths of 18
      genera of fishes (81 samples) divided into 3 groups: saltwater fish (13 genera),
      freshwater fish except for the carp family (3 genera) and carp family fish (2
      genera). The otoliths and the living environments were compared. The chemical
      composition was analysed using a synchrotron X-ray fluorescence analyser.
      RESULTS: Bottom fishes generally have larger saccular otoliths, and migrating
      fishes have smaller saccular otoliths. In comparing the bottom/reef fishes and
      the migrating fishes in salt water, the former tended to have larger saccular
      otoliths. In saltwater bottom fishes the tendency was found that the thinner the
      head, the larger was the saccular otolith. We found significant quantities of
      iron, zinc and manganese in the lagenar otoliths.

PMID- 18607890
TI  - Endoscopic resection of chordomas in different clival regions.
AB  - CONCLUSION: The endoscopic approaches developed for the treatment of the
      chordomas according to the different clival location provide the possibility for
      more complete tumor resection with maximal preservation of anatomic structures
      and reduction of the overall incidence of complications. OBJECTIVE: The endoscope
      has recently been applied in patients with chordomas, but rare studies report the
      various endoscopic approaches in the treatment of chordomas in the different
      regions of clivus. In this study, the authors present their experience with these
      techniques in patients with chordomas. PATIENTS AND METHODS: Four chordomas in
      the upper-middle clivus underwent an endoscopic transseptal transsphenoidal (ETT)
      approach. Five macro-chordomas involving whole clivus underwent an extended ETT
      approach. Three chordomas in the lower clivus underwent an endoscopic
      transoropharyngeal (ETOP) approach. The surgical access points were designed for
      each patient. After safe planes were identified along the surgical access points,
      the tumor was fractionally removed. RESULTS: Seven gross total, four subtotal,
      and one partial resection were achieved after surgery. At 6 months to 3 years
      follow-up, eight patients were recurrence-free and two patients had unchanged
      residual tumor. One patient with recurrent chordoma underwent second surgery and
      subsequent intensity modulated radiation therapy (IMRT). The other patient with a
      recurrent chordoma died 1 year postoperation.

PMID- 18607891
TI  - Down-regulation of toll-like receptor 4 in the granulation tissues of
      postoperative mastoid cavities with otorrhea.
AB  - CONCLUSIONS: The expression of toll-like receptor (TLR) 4 and associated
      downstream events, such as the activation of signal pathway proteins and
      inflammatory cytokine production, were down-regulated in the granulation tissues
      of postoperative mastoid cavity with otorrhea, possibly leading to endotoxin
      tolerance. OBJECTIVE: The postoperative mastoid cavity is exposed to a high
      density and diversity of bacteria, but very little is known about how the immune
      environment is maintained in these regions with otorrhea. In this study, we
      investigated the changes in the TLR2 and TLR4 signaling pathways and inflammatory
      cytokine production in the granulation tissues of mastoid cavities with otorrhea
      and in normal auditory canal skin. MATERIALS AND METHODS: We investigated the
      expression of TLR2 and TLR4, as well as downstream signal pathway proteins,
      nuclear factor-kappaB (NF-kappaB) DNA binding, and secretion of tumor necrosis
      factor-alpha (TNF-alpha) in 28 samples of granulation tissue obtained from the
      postoperative mastoid cavity with otorrhea and 10 normal external auditory canal
      skin samples. RESULTS: We found that the frequency of TLR2- and TLR4-positive
      cells was not increased in granulation tissues relative to normal skin, but the
      TLR4 mRNA and protein were down-regulated. In this pathophysiological process,
      there was also a lack of downstream signal pathway protein activation and
      secretion of TNF-alpha.

PMID- 18607892
TI  - Diagnosis and management of cervical sympathetic chain schwannoma: a review of 9
      cases.
AB  - CONCLUSIONS: Cervical sympathetic chain schwannoma (CSCS) sometimes mimics
      carotid body tumor (CBT). Differential diagnosis between these tumors is
      sometimes difficult using MRI alone. MRA, color Doppler ultrasonography, and fine
      needle aspiration (FNA) after imaging may be helpful to rule out CBT. Surgical
      resection of CSCS is relatively effortless, and Horner's syndrome is an expected
      but acceptable postoperative complication. Intratumoral hemorrhage and
      vasodilation may be the main reasons for significant enhancement on MRI.
      OBJECTIVES: CSCSs are rare and known to mimic carotid body tumors. We report 9
      cases of CSCS with an emphasis on imaging, surgical management, and pathological
      findings. Moreover, we describe the differential diagnosis of CSCS and CBT, and
      speculate the reasons behind significant enhancement on MRI. PATIENTS AND
      METHODS: Nine cases of CSCS treated at a tertiary referral center between 1996
      and 2008 were reviewed. RESULTS: MRI revealed 3 of 9 cases (33%) splayed the
      carotid bifurcation and displayed marked contrast enhancement with gadolinium.
      All patients underwent surgical excision of the mass with minimal blood loss.
      Postoperative Horner's syndrome was encountered in all patients, which required
      no treatment. Marked gadolinium enhancement tended to be associated with
      histological findings such as intratumoral hemorrhage and vasodilation.

PMID- 18607893
TI  - Reconstruction of full-thickness nasal defect by free anterolateral thigh flap.
AB  - CONCLUSION: Because of minimal donor region morbidity, pliability, the presence
      of long and large caliber vessels, and lack of visible scar, the free
      anterolateral thigh flap provides an ideal option for restoration of full
      thickness nasal defects. OBJECTIVE: Full-thickness nasal defect reconstruction
      requires internal nasal lining and external cover. In large defects, internal
      nasal lining replacement with traditional sources may not be expedient. We
      describe reconstruction of full-thickness nasal defects with free anterolateral
      thigh flap. PATIENTS AND METHODS: From August 2005 to July 2007, six patients
      with full-thickness nasal defects underwent nasal reconstruction using free
      anterolateral thigh flap. All defects resulted from tumor resections. Four
      patients had a basal cell carcinoma, one an epidermoid carcinoma, and the other
      patient had recurrent malignant fibrous histiocytoma. RESULTS: All flaps survived
      completely. The average hospitalization time was 3 days. No complication was
      observed.

PMID- 18607894
TI  - Effects of hydrogen peroxide on vestibular hair cells in the guinea pig:
      importance of cell membrane impairment preceding cell death.
AB  - CONCLUSION: Our findings indicate that oxidative stress induces morphological
      changes in vestibular hair cells and subsequently leads to cell death after 2.5
      h. OBJECTIVES: The aim of this study was to confirm the direct effects of
      oxidative stress on vestibular hair cells. MATERIALS AND METHODS: Vestibular hair
      cells isolated from guinea pigs were loaded with 1 or 10 mM H2O2, and
      morphological changes were observed. In addition, in a viability/cytotoxicity
      assay system, the numbers of dead cells in isolated cristae ampullares were
      counted 1, 3, and 5 h after loading with H2O2 or artificial perilymph (control).
      RESULTS: Reactive oxygen, in the form of H2O2, directly affects the cell membrane
      of isolated vestibular hair cells and causes swelling of the cell body, bleb
      formation, and shortening of the neck region. Morphological changes occur within
      30 min after loading with H2O2, but a significant increase in the number of dead
      cells is noted only after 3 h.

PMID- 18607895
TI  - Therapeutic influence on circulating and monocyte-derived dendritic cells in
      laryngeal squamous cell carcinoma patients.
AB  - CONCLUSION: Surgical resection of laryngeal squamous cell carcinoma (LSCC) could
      be associated with improved circulating myeloid dendritic cell (mDC) number and
      monocyte-derived dentritic cell (MoDC) function. Although adjunctive radiotherapy
      after surgery did not effect the normalization of mDC number, it may have an
      impact on MoDC function. OBJECTIVE: To investigate the effects of surgery and
      adjunctive radiotherapy on both circulating dendritic cells (DCs) and MoDCs of
      LSCC patients. SUBJECTS AND METHODS: Forty-six patients with LSCC and 15 age
      matched healthy control subjects were enrolled in this study. Blood samples were
      taken before, during, and after conventional treatment from both patients who
      underwent surgery only (n=18) and those who had adjunctive radiotherapy after
      tumor removal (n=28). Three-color flow cytometry was used for determination of
      circulating DC subsets. Moreover, MoDCs were generated utilizing granulocyte
      macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), then the
      phenotype of MoDCs was measured by flow cytometry and the ability to stimulate
      autologous T cells was tested in a mixed leukocyte reaction (MLR). RESULTS: The
      preoperative mDC counts, MoDC surface molecular expression and stimulatory
      capacity were impaired in patients in comparison with controls. The number of
      mDCs and the expression of CD80, CD83, and HLA-DR on MoDCs were significantly
      increased as compared with those pretreatment in patients who underwent surgery
      only and in those who had surgery followed by adjunctive radiotherapy. However,
      the recovery of CD86 expression and allostimulatory activity was only observed in
      patients who underwent surgery alone.

PMID- 18607896
TI  - A comparison of the hearing results of KTP and Erbium YAG laser stapedotomy.
AB  - CONCLUSION: Our data prove that lasers are safe and useful instruments in stapes
      surgery. Good postoperative results can be attained in both KTP and Er: YAG
      lasers. There was no significant inner ear damage related to the Er: YAG laser
      use. OBJECTIVE: To compare the postoperative results of stapedotomies performed
      with KTP and Erbium: YAG lasers in patients with otosclerosis in order to assess
      the risk of Er: YAG for the inner ear. PATIENTS AND METHODS: The charts of 152
      consecutive adult patients who underwent primary laser stapedotomies for
      otosclerosis from 1999 to 2005 were reviewed. One hundred and thirty-seven
      stapedotomies (98 patients) were performed using the KTP laser and 54
      stapedotomies (54 patients) were performed with Er: YAG laser. All the patients
      were separated in two groups according to the type of laser, which was used.
      Hearing results were analyzed according to the Committee on Hearing and
      Equilibrium Guidelines of the American Academy of Otolaryngology-Head and Neck
      Surgery. Pure-tone audiometry was performed before the surgery, three months and
      one year postoperatively. RESULTS: The study indicated that KTP and Er: YAG
      stapedotomies have similar rates of the air-bone gap closure. There was no
      significant postoperative sensorineural hearing loss found in both techniques.

PMID- 18607897
TI  - Clinical outcome following radiotherapy and planned neck dissection in N+ head
      and neck cancer patients.
AB  - CONCLUSIONS: This study confirms earlier findings that patients with viable
      tumour cells in the neck after external beam radiotherapy (EBRT) have a poor
      prognosis. The study also indicates that neck dissection (ND) does not change the
      prognosis for patients with a complete clinical response in the neck. At the
      moment our guidelines concerning this matter are being reviewed. OBJECTIVES: The
      protocol at our institution stipulates a planned ND in patients with metastasis
      in the neck after EBRT regardless of the response in the neck. As the necessity
      for a planned ND has not been clarified we wanted to evaluate our results.
      PATIENTS AND METHODS: Patients diagnosed from 1998 to 2002 with metastasis in the
      neck who received EBRT were evaluated for histopathological findings and clinical
      outcome. RESULTS: A total of 156 patients were included. Overall survival was 62%
      and disease-specific survival was 76%. There was a complete response (CR) in the
      neck in 63 patients (40%); among these 15 had viable tumour cells in the neck. In
      patients not achieving CR, 40% (37/93) had viable tumour cells left in the neck.
      Patients with viable tumour cells in the neck after EBRT had disease-specific
      survival of 48% compared with 90% among patients without viable tumour cells.

PMID- 18607900
TI  - Changes in the characteristics of definite Meniere's disease over time in Japan:
      a long-term survey by the Peripheral Vestibular Disorder Research Committee of
      Japan, formerly the Meniere's Disease Research Committee of Japan.
AB  - CONCLUSION: The incidence of new cases of Meniere's disease (MD) in elderly
      patients aged 60 years or more was found to have increased over time after
      correction for age distribution in the overall population. Job- and care-related
      fatigue may be involved in the recent increase in elderly-onset cases because
      physical and mental fatigue can induce onset of the disease. OBJECTIVES: Changes
      over time in the epidemiologic characteristics of MD in Japan were analyzed.
      MATERIALS AND METHODS: Between 1975 and 2006, four nationwide, multi-center
      surveys of MD were conducted by the Meniere's Disease Research Committee of Japan
      (1975-1976) and the Peripheral Vestibular Disorders Research Committee of Japan
      (1982-1984, 1990, and 2001-2006). Information was collected by the committee
      members on a total of 1368 de novo cases of definite MD, 520 reported in the
      first survey, 290 in the second survey, 148 in the third survey, and 410 in the
      fourth survey. RESULTS: Clear changes were seen over time in the population
      adjusted sex distribution of the disease and population-adjusted age at onset.
      The number of definite MD cases in females increased over time relative to the
      number of cases in males. The proportion of cases in which onset occurred at 60
      years of age or more increased over time when the number of cases in each age
      group was adjusted for changes in age distribution of the population over time.
      From the time of the third survey, there was a slight increase in the proportion
      of cases with bilateral involvement.

PMID- 18607901
TI  - Evaluation of a model for studies on sequelae after acute otitis media in the
      Mongolian gerbil.
AB  - CONCLUSIONS: The model appears relevant for studies on sequelae after acute
      otitis media (AOM), and may be the seed of a new, chronic tympanic membrane
      perforation model in the gerbil. OBJECTIVES: To evaluate an experimental model
      for abortive otitis media and to assess the structural and functional changes of
      the tympanic membrane in the resolving phase. MATERIALS AND METHODS: The middle
      ears of 16 Mongolian gerbils were inoculated with type 6a Streptococcus
      pneumoniae. Half of the animals were treated with antibiotics on days 4-6, when
      otoscopy was performed as well. After 1, 2, 3 or 4 weeks the animals were
      sacrificed and their tympanic membranes were examined by otoscopy, dissection
      microscopy, light microscopy and moire interferometry. RESULTS: On days 4 and 6
      AOM was produced in approximately 80% of the animals and perforations prevailed
      in approximately 30% at the study end points. Clinical signs of AOM and oedema of
      the tympanic membrane had already started to reduce after 1 week, and often
      resolved within 2 weeks. The mechanical stiffness of the tympanic membrane
      remained relatively unharmed in the non-perforated ears. The antibiotic treatment
      seemed to reduce the duration of oedema but not the perforation rate.

PMID- 18607902
TI  - Universal newborn hearing screening programs in Italy: survey of year 2006.
AB  - CONCLUSION: Our results suggest a rapid diffusion of newborn hearing screening
      programs in Italy and indicate that three conditions seem to play a crucial role
      in the implementation of Universal Newborn Hearing Screening (UNHS) programs: the
      size (>800 births/year) and location (metropolitan urban areas) of the hospital,
      and the presence of an audiologist in the UNHS coordinating team. OBJECTIVES: The
      aim of this paper is to provide data on the degree of implementation and coverage
      of UNHS programs in Italy. MATERIALS AND METHODS: Data were collected through a
      Screening Survey Questionnaire that was sent to all birthing hospitals active in
      Italy in 2006 and was filled in by the chief of the hospital or by the UNHS
      program coordinator. RESULTS: In Italy UNHS coverage had undergone a steep
      increase from 29.3% in 2003 (156,048 newborns screened) to 48.4% in 2006 (262,103
      screened). The majority of UNHS programs were implemented in the two most
      economically developed areas, i.e. in the north-west area (79.5%, 108,200 of
      136,109 births), and in the north-east area (57.2%, 52,727 of 92,133 births),
      while a limited diffusion still remains in some areas, typically in the islands
      (11.3%, 7158 of 63,460 births).

PMID- 18607904
TI  - The role of fine-needle aspiration cytology and magnetic resonance imaging in the
      management of parotid mass lesions.
AB  - CONCLUSION: Fine-needle aspiration cytology (FNAC) is the diagnostic modality of
      first choice for characterization of parotid mass lesions, while magnetic
      resonance imaging (MRI) should not be requested routinely. MRI can be reserved
      until FNAC shows the indication for surgical intervention. OBJECTIVES: Although
      both FNAC and MRI are useful preoperative diagnostic modalities for parotid mass
      lesions, it is not well established which modality is more effective. In the
      present study we sought to address the relative value of FNAC and MRI in relation
      to the differential diagnosis of benign and malignant parotid mass lesions.
      SUBJECTS AND METHODS: Eighty-one patients with parotid mass lesions (60 benign
      and 21 malignant) who had preoperatively undergone FNAC and MRI were reviewed
      retrospectively. RESULTS: Unsharp margin and infiltration into adjacent tissues
      on MRI significantly correlated with a malignant histology. The
      sensitivity/specificity/accuracy of FNAC and MRI were 90%/95%/94% and
      81%/92%/89%, respectively. Either FNAC or MRI served equally to predict the
      malignant nature of parotid mass lesions. Furthermore, the combination of FNAC
      and MRI yielded no diagnostic advantage over either modality alone. Accurate
      histological typing rates by FNAC were 80% and 62% for benign and malignant
      lesions, respectively.

PMID- 18607908
TI  - Simvastatin treatment induces morphology alterations and apoptosis in murine
      cochlear neuronal cells.
AB  - CONCLUSION: Simvastatin presented neurodegenerative morphological changes and
      cell death via its specific inhibition of mevalonate pathway induced apoptosis in
      cultured cochlear neuronal cells. These findings might contribute to
      understanding the auditory neurobiological effects of HMG-CoA reductase
      inhibitors. OBJECTIVES: The statins are 3-hydroxy-3-methylglutaryl-coenzyme A
      (HMG-CoA) reductase inhibitors that are widely used as anti-hypercholesterol
      drugs because of their beneficial cardiovascular effects. However, the effects of
      statins in neuronal cells are controversial, and no studies have examined the
      effect of statins in cochlear neuronal cells. The objective of this study was to
      evaluate the direct effect of simvastatin on cochlear neuronal cells and examine
      the mechanisms underlying these effects. MATERIALS AND METHODS: Cultured mouse
      cochlear neuroblasts (VOT-33) and primary rat cochlear explants containing spiral
      ganglion neurons were treated with simvastatin in the absence or presence of
      mevalonate. RESULTS: Simvastatin caused a loss of the cytoplasmic projections in
      VOT-33. In primary rat cochlear nerve cells, simvastatin decreased staining for
      NF200, a neuro-cytoskeletal protein. We also found that simvastatin-induced VOT
      33 apoptosis, as indicated by accumulation of the sub G0/G1 fraction, DNA-ladder
      formation, and caspase-3 activation. The above-mentioned effects were abolished
      by mevalonate treatment.

PMID- 18607909
TI  - Hereditary hemorrhagic telangiectasia type 1 and 2 mutations in Finland.
AB  - CONCLUSION: The finding of several new unique mutations suggests that the genes
      causing hereditary hemorrhagic telangiectasia (HHT), i.e. endoglin (ENG) and
      activin receptor-like kinase 1 (ACVRL1), have a relatively high mutation rate. As
      no single founder mutation was found, analysis of the whole coding sequences of
      ENG and ACVRL1 genes remains the first choice in genetic testing of new index
      patients with HHT. OBJECTIVES: Our aim was to characterize specific mutations
      causing HHT in our hospital in Helsinki serving a population of 1 million
      inhabitants. PATIENTS AND METHODS: HHT patients were searched from our hospital
      discharge records and their diagnoses were verified by review of patient records
      and interviews. Eight index patients who fulfilled HHT phenotypic criteria were
      tested. ENG and ACVRL1 mutations were identified by DNA sequencing of ENG and
      ACVRL1 coding regions. RESULTS: Of the eight index patients, four had a mutation
      in the ENG gene, three in the ACVRL1 gene, and one had no mutations. All the
      mutations were different and all the four ENG mutations and one of the ACVRL1
      mutations were new and had not been described previously in other populations.
      All the affected first-degree relatives had the same mutation as the index case.

PMID- 18607910
TI  - Early timing of low-dose dexamethasone decreases inflammation in a murine model
      of eosinophilic airway disease.
AB  - CONCLUSION: A very low dose of dexamethasone (DEX) was as equally as sufficient
      as a pharmacological dose to decrease eosinophil inflammation in airways and bone
      marrow. The timing of DEX treatment in relation to allergen challenge was
      strongly decisive for the outcome of the inflammatory response. OBJECTIVES: We
      aimed to study compartmental allergic airway inflammatory responses to classic
      pharmacological and also extremely low physiological DEX dosage, given at
      different time points close to allergen challenge in a murine model. MATERIALS
      AND METHODS: Ovalbumin-sensitized BALB/c-mice were exposed to intra-nasal
      ovalbumin. DEX was given i.p. as 1 microg/kg low-dose or 500 microg/kg
      pharmacological single-dose 2 h before, immediately before or 7 h after each of
      three challenges. Inflammatory cells were evaluated in bronchoalveolar lavage
      (BAL), lungs, nasal mucosa, and bone marrow. RESULTS: Groups treated with low
      dose DEX decreased eosinophilia in BAL to the same extent as the pharmacological
      dose, but only when administered before challenge. The most prominent decrease of
      eosinophils in BAL was seen in mice treated with the low dose 2 h before
      challenge. A similar response pattern as in BAL eosinophilia was detected in lung
      histopathology. DEX treatments had no obvious effects on inflammation in nasal
      mucosa.

PMID- 18607911
TI  - Cochlear blood flow during occlusion and reperfusion of the anterior inferior
      cerebellar artery--effect of topical application of dexamethasone to the round
      window.
AB  - CONCLUSION: Topical application of dexamethasone may support autoregulation of
      cochlear blood flow (CBF), although it had no direct effect on CBF. OBJECTIVES:
      Although intratympanic steroid therapy for patients with inner ear disorders is
      common, the mechanism by which steroids exert their effect is unclear. We
      investigated the response of CBF to topical application of dexamethasone onto the
      round window. MATERIALS AND METHODS: Two concentrations of dexamethasone (3.3
      mg/ml and 33 mg/ml dexamethasone in 0.5 microl saline) were applied to the round
      windows of rats, and CBF responses were measured using a laser Doppler flowmeter.
      The effects on CBF of a 2 h occlusion of the anterior inferior cerebellar artery
      (AICA) and subsequent release of the clamp with or without previous dexamethasone
      application were investigated. RESULTS: No significant change in CBF was observed
      after topical application of dexamethasone, and it did not affect the decrease in
      CBF caused by AICA occlusion. However, recovery of CBF after release of the AICA
      clamp was better in animals treated with dexamethasone than in those that did not
      receive dexamethasone.

PMID- 18607913
TI  - Comparative study of patients with and without sentinel lymph node biopsy (SLNB)
      in oral and oropharyngeal cancer: is SLNB an accurate and useful procedure?
AB  - CONCLUSION: Sentinel lymph node biopsy (SLNB) is a technique that facilitates the
      study of metastasis in oral and oropharyngeal cancer and reduces morbidity in
      patients affected by this pathology. OBJECTIVES: Oral and oropharyngeal cancers
      are common and are frequently associated with spread to cervical lymph nodes. We
      attempted to confirm the usefulness of SLNB in patients suffering from squamous
      cell carcinoma of the oral cavity as a prognostic technique for lymph node
      prediction of micrometastatic invasion. Using surgical parameters, we compared
      its relevance against a retrospective group without SLNB. PATIENTS AND METHODS:
      We studied a prospective group of 22 patients, 21 men and 1 woman, aged 40-83
      years (mean=57.77, SD=13) in which SLNB was performed and a retrospective group
      of 22 patients, 19 men and 3 women, aged 34-76 years (mean=52.68, SD=11) in which
      SLNB was not performed. Both groups presented oral cavity tumors at clinical
      stages T1-T3 and radiological stage N0. SLNB consisted of preoperative
      lymphoscintigraphy (LG), intraoperative detection of the sentinel lymph node
      (SLN), and a histopathological examination following the recommendations of the
      Association of Directors of Anatomic and Surgical Pathology (ADASP) and the
      Canniesburn protocol. RESULTS: We observed SLNs in 21 of 22 patients, with a
      total of 32 SLNs detected at cervical level II (65.63%), I (21.87%), and III
      (12.5%). SLNB displayed a sensitivity of 73% (confidence interval (CI)=0.51-0.99)
      and 100% specificity (CI=1). Negative and positive predictive values were 80% and
      100%, respectively. SLNB significantly reduced the incidence of radical neck
      dissection (p=0.003), the need for recovery/resuscitation beds after surgery
      (p=0.002), surgical complications (p=0.034), and length of hospital stay
      (p=0.01).

PMID- 18607914
TI  - Results of revision mastoidectomy.
AB  - CONCLUSIONS: Successful canal wall down (CWD) mastoidectomy requires removal of
      all diseased air cells, lowering of the facial ridge to the mastoid segment of
      the facial nerve, complete removal of the lateral epitympanic wall, and
      amputation of the mastoid tip. Additionally, the inferior canal wall should be
      lowered to adequately expose the hypotympanum, which allows a smooth transition
      into the mastoid cavity. An adequate meatoplasty is also necessary. Closed
      supratubal recess should be opened, anulus and tympanic membrane remnant should
      be removed in CWD cases. Revision mastoidectomy has a high success rate in
      obtaining a dry and epithelialized ear. OBJECTIVE: This study reports revision
      mastoidectomy results and indicates factors that must receive attention in
      chronic otitis media surgery to produce less revision surgery. PATIENTS AND
      METHODS: Thirty-five patients who underwent revision mastoidectomy with or
      without cholesteatoma between 2005 and 2008 were analyzed retrospectively.
      Patients who had revision mastoidectomy with previous intact canal wall (ICW) or
      CWD mastoidectomies were included in the study. RESULTS: Patients were aged 32-69
      years (mean 57.4). There were 22 female and 13 male patients. Revision
      mastoidectomies were applied to 14 previous ICW and 21 prior CWD mastoidectomies.
      Of the 35 patients, 24 patients had cholesteatoma and 11 of them did not. Of the
      patients who had revision surgery, 10 had ICW mastoidectomy and 25 had CWD
      mastoidectomy. After revision mastoidectomy, at 3-25 months follow-up (mean 16.7
      months), 29 patients had been successfully treated; they had dry well
      epithelialized cavity, with no findings of persistent, recurrent discharge or
      granulation tissue and cholesteatoma. In 21 patients in whom revision CWD
      mastoidectomy was performed, causes of failure of previous ear surgery in order
      of frequency were recurrent or persistent cholesteatoma and narrow meatoplasty
      (80.9%), persistent sinodural angle air cells and close supratubal recess
      (71.4%), high facial ridge and inadequate canalplasty (66.7%), persistent
      tegmental air cells and tympanic membrane remnant (57.1%), persistent mastoid
      apex air cells and open eustachian orifice (52.4%). Causes of failure after our
      revision ICW mastoidectomy in order of frequency were persistent or recurrent
      cholesteatoma (78.6%), closed supratubal recess (64.3%), persistent sinodural
      angle air cells, inadequate canalplasty and persistent mastoid apex air cells
      (57.1%), persistent tegmental air cells (42.9%).

PMID- 18607915
TI  - Association of single nucleotide polymorphisms in GATA-3 with allergic rhinitis.
AB  - CONCLUSION: The results of our study demonstrated the association between the
      single nucleotide polymorphisms (SNPs) of GATA-3 and allergic rhinitis (AR).
      OBJECTIVE: AR is considered to be controlled by T-helper type 2 (Th2) cells. GATA
      3 is the crucial transcription factor controlling the differentiation and
      function of Th2 cells. We aimed to evaluate the association between the SNPs of
      GATA-3 and AR. SUBJECTS AND METHODS: GATA-3 SNPs in 109 AR patients and 112
      healthy controls in China were detected with restriction fragment length
      polymorphism. RESULTS: The genotypes at rs1269486 were GG, GA, and AA, and the
      genotypes at rs2229360 were CC, CT, and TT. The frequency of the G allele in the
      patient group was significantly higher than that in the control group (p<0.01),
      while the frequency of the A allele in the patient group was significantly lower
      than that in the control group (p<0.01). Meanwhile, the haplotype frequency of GC
      at the two loci in the patient group was significantly higher than that in the
      control group (p<0.01), and the haplotype frequency of AC in the patient group
      was significantly lower than that in the control group (p<0.01).

PMID- 18607916
TI  - Functional blood flow patterns of the endolymphatic sac in the rat.
AB  - CONCLUSION: Visualization of the endolymphatic sac vascular network under video
      fluorescence microscopy showed a typical microvascular organization. The
      microvascular arrangement and the microcirculation may reflect a functional state
      of the endolymphatic sac. Damage or change of the blood circulation following
      endolymphatic sac surgery is discussed. OBJECTIVES: To visualize and study the
      dynamic microcirculation of the endolymphatic sac in live rats. METHOD: An
      experimental animal study using in vivo video fluorescence microscopy. RESULTS:
      Visualization of the endolymphatic sac vascular network showed a typical
      microvascular organization. The endolymphatic sac appeared hypervascular and
      independent from other vascular systems. The microcirculation of the
      endolymphatic sac was supplied by ramification of a single artery, while venous
      trunks perpendicular to the length of the endolymphatic sac served as return
      paths for the microcirculation. The blood flow pattern was highly variable
      between rats.

PMID- 18607917
TI  - Severe deep neck space infections and mediastinitis of odontogenic origin:
      clinical relevance and implications for diagnosis and treatment.
AB  - CONCLUSIONS: Early diagnosis and aggressive antimicrobial and surgical treatment
      are essential to successfully treat extensive cervico-mediastinal abscesses of
      odontogenic origin. Patient management should be performed by experienced
      clinicians well trained in managing possible complications. We recommend close
      clinical and radiological postoperative follow-up investigations with early
      surgical re-intervention if necessary. OBJECTIVES: While neck infections
      affecting the perimandibular space have a high prevalence and their clinical
      aspects have repeatedly been discussed, further spread of the inflammation and
      life-threatening situations have rarely been described. The objective was to
      determine clinical, diagnostic, and therapeutic aspects of severe neck infections
      of odontogenic origin. Emphasis was placed on grave descending deep neck space
      infections, sometimes resulting in mediastinitis as a life-threatening
      complication. PATIENTS AND METHODS: We reviewed 10 patients with severe
      odontogenic abscesses treated during an 8-year interval in a single center.
      RESULTS: The submandibular space was the most frequently encountered location of
      deep neck space infections. Mediastinitis was found in five patients. The most
      frequent causative bacteria were Streptococcus and Bacteroides species. All
      patients underwent intravenous antibiotic treatment and surgical therapy.
      Mediastinotomy was inevitable in five cases and thoracotomy in one case. All
      patients survived.

PMID- 18607919
TI  - Lateral pharyngotomy extended by resection of the mandibular angle-an alternative
      approach to the surgical treatment of oropharyngeal (tonsillar) cancers.
AB  - CONCLUSION: The authors found the procedure, when used with the proper
      indications, to be an uncomplicated and expeditious method that presents little
      risk to surrounding structures, has no residual cosmetic or functional
      consequences for the patient, presents a low risk of complications, and has a
      good oncological outcome. The main indications for this procedure are related to
      the extent of the tumour and the surgeon's experience with the method.
      OBJECTIVES: This study assessed the radical extent of each surgery, which was
      determined histopathologically, local and general complications to determine the
      safety of the procedure, and oncological and post-operative efficacy. METHOD: In
      the 1970s, Tichy described, in Czech literature, an approach to treating
      oropharyngeal tumours through a lateral pharyngotomy with the approach extended
      by resection of the mandibular angle. From 2000 to 2006 the authors use this
      method to treat 63 patients having oropharyngeal cancer in various stages (T1
      19%, T2 46%, T3 14%, T4 21%). RESULTS: Microscopically, the operation was non
      radical in three cases (4.8%). Of the local complications encountered,
      pharyngocutaneous fistulas were the most frequent, three cases (4.8%), and
      postoperative bleeding was seen in two cases (3.2%). General complications were
      seen in four cases (6.4%).

PMID- 18607918
TI  - Delayed electrical stimulation and BDNF application following induced deafness in
      rats.
AB  - CONCLUSION: Under the condition of delayed intervention (30 days after deafening)
      following gentamicin+furosemide deafening in rats, we conclude that chronic
      intracochlear electrical stimulation (ES) and continuous intracochlear
      administration of brain-derived neurotrophic factor (BDNF) enhance spiral
      ganglion cell (SGC) body and peripheral process survival and improve auditory
      sensitivity. Moreover, the combination of ES and BDNF has a synergistic
      protective effect rather than an additive effect. Both SGC body and peripheral
      process influence the auditory sensitivity, and the latter appears to be more
      important. OBJECTIVE: To determine the influence of delayed application of
      combined ES and neurotrophins on the survival of SGC body and peripheral
      processes after induced deafness in the rat. This study also explored the
      relationship between auditory sensitivity and SGC/peripheral process density.
      MATERIALS AND METHODS: The left cochlea of profoundly deafened rats was implanted
      with an electrode and drug-delivery system 30 days after deafening. BDNF or
      artificial perilymph (AP) was delivered continuously for 28 days. Experimental
      animals received ES with or without BDNF (BDNF+ES and ES+AP), and control animals
      received BDNF or AP without ES (BDNF and AP). The right cochleae of the animals
      served as deafened untreated controls. Electrically evoked auditory brainstem
      responses (EABRs) were recorded immediately after surgery and every 7 days.
      RESULTS: In the AP group, EABR thresholds demonstrated a systematic and rapid
      increase throughout the treatment period after the deafening procedure and
      electrode implantation. However, in the other three treatment groups, EABR
      thresholds showed a slow increase at the beginning and then slow decrease. The
      thresholds of the BDNF and ES+AP groups were significantly less than those of the
      AP group from day 7 to 28 and those of the BDNF+ES group were significantly less
      than those of other three groups from day 21 to 28, indicating that BDNF infusion
      and chronic ES have a synergistic effect rather than an additive effect. In terms
      of SGC and peripheral process density, the difference between the treated and
      control ears of BDNF, ES+AP, and BDNF+ES groups was clearly significant. Analysis
      of the SGC/peripheral process density of the left cochlea across the treatment
      groups demonstrated that SGC/peripheral process density of the BDNF and ES+AP
      groups was significantly greater than that of the AP group and the density of the
      BDNF+ES group was significantly greater than that of the other three groups,
      indicating that BDNF infusion and chronic ES have a synergistic effect rather
      than an additive effect. Finally, a functional formula was developed relating the
      last EABR threshold and SGC density and process density.

PMID- 18607920
TI  - The roles of local inhibition mediated by gamma-aminobutyric acid (GABA)-A
      receptor in duration tuning in the inferior colliculus of guinea pigs.
AB  - CONCLUSION: GABA-mediated inhibition is responsible for the duration tuning in
      the inferior colliculus (IC) of guinea pigs, a non-echo-locating mammal. Duration
      tuning in this species is better demonstrated in an appropriate short time
      window. OBJECTIVES: To investigate the role of GABA-mediated inhibition in
      duration tuning of neurons in the IC of guinea pigs. MATERIALS AND METHODS:
      Duration tuning pattern was recorded by measuring the spikes of single neurons in
      response to broadband noise of different durations. The effect of GABA-mediated
      inhibition was verified by comparing the responses with and without the use of
      the GABA-A receptor blocker bicuculline (BIC), which was applied using micro
      iontophoresis. RESULTS: In addition to overall increase in responsiveness, the
      application of BIC was found to significantly reduce or eliminate the duration
      selectivity in 44 of the 67 neurons that showed clear duration tuning from a
      sample of total 340 neurons.

PMID- 18607921
TI  - A preliminary result of concurrent chemoradiation with weekly cisplatin in
      elderly nasopharyngeal carcinoma patients.
AB  - CONCLUSION: A weekly regimen of cisplatin 30 mg/m2 as concurrent chemoradiation
      (CCRT) was effective in elderly nasopharyngeal carcinoma (NPC) patients, with
      acceptable and reversible acute toxicity following CCRT therapy. OBJECTIVES: The
      purpose of this retrospective study was to evaluate the efficacy, toxicity, and
      tolerability of a multi-modal treatment strategy in elderly NPC patients.
      Subsequent systemic adjuvant chemotherapy was administered to achieve systemic
      control. PATIENTS AND METHODS: From December 2002 to December 2006, 26 NPC
      patients over 60 years of age who had stage IIB to IV NPC were evaluated in this
      retrospective analysis. The CCRT chemotherapy protocol consisted of eight weekly
      doses of cisplatin 30 mg/m2 administered in an outpatient setting. Adjuvant
      systemic chemotherapy consisted of four monthly cycles of cisplatin (20
      mg/m2/day) plus 5-fluorouracil (1000 mg/m2/day) for 5 consecutive days. Study end
      points included treatment outcome, compliance, and toxicity. RESULTS: The 2-year
      overall survival, disease-free survival, local control, and distant metastasis
      free rate were 87%, 73%, 92%, and 76%, respectively. Over 80% of patients were
      able to take more than six doses of weekly cisplatin during CCRT; however, nearly
      half of the patients had grade 3 hematological toxicity during adjuvant therapy
      requiring treatment modification or cessation of further adjuvant therapy.

PMID- 18607922
TI  - Surgery alone for squamous cell carcinoma of the oral cavity: survival rates,
      recurrence patterns, and salvage treatment.
AB  - CONCLUSION: Surgery alone may be a reliable and feasible treatment of choice in
      selected patients with squamous cell carcinoma (SCC) of the oral cavity, given
      the proper indications. OBJECTIVE: To evaluate the results of treatment of oral
      cavity SCC patients with surgery alone in a single institution. PATIENTS AND
      METHODS: Between 1992 and 2004, 76 patients with previously untreated SCC of the
      oral cavity who had surgery alone without any other adjuvant treatment modalities
      were included in our study. RESULTS: The 5-year overall rate, disease-specific
      survival rates, and locoregional control rate of all 76 patients were 69%, 83%,
      and 73%, respectively. A total of 16 patients (21%) presented with recurrences (8
      with regional recurrences, 5 with local, 2 with locoregional, and 1 with distant
      metastasis). Four (6%) of the patients with primary T1 or T2 stage and one (50%)
      of those with T4 stage had recurrence at the primary site. The regional
      recurrence rate of patients with < or = N1 and > or = N2b was 10% (6 of 59) and
      67% (2 of 3), respectively. Three of four patients who had recurrence at the
      primary site and attempted salvage treatment have been cured. However, only one
      of five patients with nodal recurrence and salvage treatment has recovered.

PMID- 18607923
TI  - Vestibulotoxicity as a consequence of systemically administered tobramycin in
      cystic fibrosis patients.
AB  - CONCLUSION: The reported prevalence of vestibulotoxicity (30.4%) in cystic
      fibrosis (CF) patients supports vestibulotoxicity screening in CF patients during
      or after tobramycin exposure. Prospective longitudinal investigation is required
      for a more specific evidence-based proposal. OBJECTIVE: To investigate the
      prevalence of tobramycin-induced vestibulotoxicity in CF patients, as it had not
      been investigated before. PATIENTS AND METHODS: In this observational cohort
      study, 23 CF patient volunteers from the Haga Teaching Hospital Adult CF centre
      who had been exposed to at least one treatment with systemically administered
      tobramycin were included. Subjective feelings of dizziness were measured using
      validated questionnaires and vestibular symptoms were assessed by physical
      examination. Electronystagmography (ENG) with caloric irrigation was used as the
      gold standard. RESULTS: Peripheral vestibular loss was found in seven patients
      (7/23 = 30.4%). Central vestibular loss was found in one patient. Analysis of the
      19 completed questionnaires showed that 12 patients (12/19 = 63.2%) did not
      experience dizziness and 3 patients (3/19 = 15/8%) experienced specific
      vestibular symptoms. The results of the questionnaire could not predict the
      results of ENG with caloric irrigation. Physical examination showed no
      abnormalities in any patients. No age- or dose-related predictive factors were
      found.

PMID- 18607925
TI  - Viral interaction: a possible contributing factor in head and neck cancer
      progression.
AB  - CONCLUSION: Human herpesvirus-8 could potentiate the effects of human
      papillomavirus (HPV)-16 on cell cycle dysregulation by up-regulating the
      transcription of HPV-16 E7, which can lead to malignant transformation of normal
      epithelial cells. OBJECTIVES: High-risk HPV-16 is known for its association with
      development of head and neck carcinoma, leading to considerable morbidity and
      mortality worldwide. HPV-16 produces two early proteins, E6 and E7, that can
      disrupt the cell cycle and transform cells. Other viruses may potentiate
      dysregulation of the cell cycle by HPV-16. Herpes viruses are known to produce
      replication transcription activators, which may contribute to the malignant
      transformation of normal cells. This study aimed to determine if the ORF50/Rta
      protein of HHV-8 binds to genomic regions within HPV-16 and alters the
      transcription and/or translation of E6 and E7 in HPV-infected cells. MATERIALS
      AND METHODS: Protein shift assays determined the binding potential of ORF50 to
      various HPV-16 genomic regions. A real-time polymerase chain reaction (PCR) assay
      quantified the effect of ORF50 on the transcription of E6 and E7 within these
      cells. Finally, immunofluorescent confocal microscopy was used to quantify E6 and
      E7 protein levels within transfected cells and study their localization patterns.
      RESULTS: The results reveal potential ORF50/Rta binding sites within HPV-16 and a
      significant up-regulation of E7 transcription in ORF50 transfected cells.

PMID- 18607926
TI  - Benchmarking surgery: secondary post-tonsillectomy hemorrhage 1999-2005.
AB  - CONCLUSIONS: We found no evidence that the reported increase in otolaryngologic
      surgery in Norway in recent years has affected post-tonsillectomy hemorrhage
      rates, and suggest that the latter is a valuable benchmark for the quality of the
      tonsillectomies and adenotonsillectomies nationwide. OBJECTIVES: To estimate the
      incidence of post-tonsillectomy hemorrhage and assess the distribution of
      hospitalizations for post-hemorrhage bleeding and surgery. MATERIALS AND METHODS:
      This was a national study using data from the Norwegian Patient Registry 1999
      2005 with complete information on the incidence of post-hemorrhage
      hospitalizations, rebleeding surgery, and (adeno)tonsillectomy rates. RESULTS:
      One patient per 200 tonsillectomies was hospitalized and 1 per 1000 operated for
      post-tonsillectomy hemorrhage during the study period. Of the 328 patients
      hospitalized, 64 (20%) required surgery under general anesthesia. Peak age was 5
      9 years; 194 (59%) with post-tonsillectomy hemorrhage were males. The mean
      rebleeding rate was 0.5% (confidence interval (CI)=0.5-0.6) when secondary
      rebleeding was estimated as the proportion of all tonsillectomies. While
      tonsillar surgery was more frequent in the non-adult population, post
      tonsillectomy surgery was equally common in the ages below and above 16 years.
      Seasonal variation in post-tonsillectomy hemorrhages was not found.

PMID- 18607927
TI  - Metastasis to the submandibular gland in oral cavity squamous cell carcinomas:
      pathologic analysis.
AB  - CONCLUSION: This study demonstrates that the incidence of submandibular gland
      metastasis in oral cavity squamous cell carcinoma (SCC) is extremely rare and its
      involvement is through direct extension from a primary lesion. Therefore, if the
      primary lesion of the oral cavity carcinoma is not in close proximity and hence
      does not provide suspicion of direct extension, it may be safe to preserve the
      submandibular gland. OBJECTIVES: Radiotherapy may lead to injury to the salivary
      glands resulting in xerostomia. This study aimed to determine whether and how the
      submandibular gland is involved in metastases of SCC of the oral cavity and to
      provide an oncological basis for preservation of the submandibular gland.
      PATIENTS AND METHODS: This study reviewed the records and pathologic specimens of
      201 patients who were diagnosed as having oral cavity SCC and underwent surgery
      at our institution, from 1991 to 2006, and pathologic metastasis to submandibular
      gland was evaluated. RESULTS: In all, 44 cases (21.9%) were found to show
      ipsilateral level I metastasis on pathologic examination. Only two cases (1%) had
      carcinoma involvement in the submandibular gland. Both these two cases had direct
      extension from a primary lesion (retromolar trigone and floor of mouth) and no
      submandibular glands showed pathologic evidence of isolated metastasis or local
      extension of metastatic lymph nodes.

PMID- 18607928
TI  - Can patients with head and neck cancers invading carotid artery gain survival
      benefit from surgery?
AB  - CONCLUSION: Surgical treatment of carotid invasion may give an improved 2-year
      survival in selected patients without significant morbidity. OBJECTIVE: To
      evaluate survival outcomes in patients with head and neck squamous cell
      carcinomas invading the carotid artery. PATIENTS AND METHODS: At the time of
      carotid invasion, 23 patients underwent surgery (n=11), chemoradiotherapy (n=6),
      or palliation (n=6). Surgical methods included carotid resection and ligation
      (n=5), carotid resection and reconstruction with saphenous vein (n=4), and
      peeling (n=2). Survival outcomes among different treatments were compared.
      RESULTS: None of the 11 surgical patients experienced perioperative mortality or
      major neurologic complications. Three of these patients survived, but two had
      recurrent disease at last follow-up; their 2-year overall survival and disease
      free survival rates were 24.5% and 18.2%, respectively. In contrast, all patients
      treated with chemoradiation or palliation died within 15 months. Median survival
      time was 16.5 months in the surgery group, 11.5 months in the chemoradiation
      group, and 3 months in the palliation group (p=0.025).

PMID- 18607929
TI  - Surgical treatment for adductor spasmodic dysphonia--efficacy of bilateral
      thyroarytenoid myectomy under microlaryngoscopy.
AB  - CONCLUSIONS: Bilateral thyroarytenoid myectomy under microlaryngoscopy by the
      Muta method (TA myectomy) is a useful surgical treatment for adductor spasmodic
      dysphonia (ADSD), as a long-term-effect can be expected. OBJECTIVE: Botulinum
      toxin (BT) injection is universally accepted as the first choice of treatment for
      ADSD. However, unfortunately it is not covered by National Health Insurance in
      Japan and therefore is not a common practice. So, various other therapeutic
      modalities have been reported. In the current study, we conducted bilateral TA
      myectomy on patients with ADSD and evaluated the results. PATIENTS AND METHODS:
      Seven patients with ADSD who visited our department between 1999 and 2005 are
      described. The details of BT injection and the surgical procedure were described
      to the patients. As all seven patients wanted to undergo this surgical therapy,
      they all underwent bilateral TA myectomy. RESULTS: The constriction was
      eliminated immediately after surgery and the patients became capable of smooth
      phonation. Hoarseness was recognized, but it began to ease after 1-2 months and
      was corrected to B grade 1-0 of the GRBAS scale approximately 6 months after the
      surgery. Improvement in the condition was noted in all seven patients according
      to evaluations based on the mora method. All patients are currently in the B
      grade 0.

PMID- 18607930
TI  - Radical scavengers for elderly patients with age-related hearing loss.
AB  - CONCLUSION: The results of this study suggest that treatment with radical
      scavengers has the potential to become an effective new therapy for age-related
      hearing loss. OBJECTIVE: To assess the efficacy of treatment with radical
      scavengers for age-related hearing loss. SUBJECTS AND METHODS: Rebamipide (300
      mg/day), alpha-lipoic acid (60 mg/day), and vitamin C (600 mg/day) were given
      orally for at least 8 weeks to 46 elderly patients with age-related hearing loss.
      RESULTS: Hearing levels after treatment were significantly improved at all
      frequencies.

PMID- 18607931
TI  - Evaluation of subjectivity in the interpretation of videonystagmography.
AB  - CONCLUSION: Subjectivity seems to play a definite role in the interpretation of
      the pendular test, but somewhat less for caloric testing, where pure visual
      analysis seems to be more reliable. Automated values provided by proof-tested
      software may be useful. OBJECTIVES: In some centers, the interpretation of
      videonystagmography is still based on direct visual analysis of recorded
      tracings. Our study addresses the importance of subjectivity in the
      interpretation of videonystagmographic readings. PATIENTS AND METHODS: Two
      experts (one junior and the other senior) were asked to interpret the same
      caloric and pendular tests on two different occasions, 3 months apart. Initial
      reading was performed without knowledge of the patient's history or the results
      of other neuro-otological tests. Three months later, interpretations were done
      with complete access to the patient's charts. The experts' answers were compared
      to the values provided by the computer software. RESULTS: For the pendular test,
      inter-expert agreement was poor. With knowledge of the patient's history, the
      expert's interpretations tended to coincide with the software's calculations. For
      the caloric test, interpretation was less variable.

PMID- 18607932
TI  - Analyses of risk factors for postoperative airway compromise following arytenoid
      adduction.
AB  - CONCLUSION: This study suggests that placing no drainage tube and postoperative
      bleeding are risk factors for postoperative airway compromise (PAC) following
      arytenoid adduction (AA). OBJECTIVES: In this study, we aimed to elucidate the
      risk factors for PAC following AA. PATIENTS AND METHODS: The data for 184
      consecutive patients who underwent AA were analyzed retrospectively. Univariate
      and forward stepwise multivariate logistic regression analyses were performed.
      RESULTS: Placing no drainage tube was a significant risk factor for PAC as
      determined by both univariate and multivariate analyses. Postoperative bleeding
      was a significant risk factor for severe airway compromise requiring emergency
      airway treatment.

PMID- 18607933
TI  - Spindle cell carcinoma as a locally recurrent malignancy after surgery for early
      lingual squamous cell carcinoma.
AB  - Spindle cell carcinoma (SpCC) of the tongue is a relatively rare malignancy. We
      treated a patient with metachronous early squamous cell carcinoma (SCC) in both
      margins of the tongue (right side first followed by left side). Eight years after
      treatment for the first SCC by surgery and radiotherapy, the second SCC occurred
      in the contralateral margin of the tongue. Surgical resection was performed for
      the second SCC, with local recurrence 8 months later associated with pathological
      change from SCC to SpCC. The SpCC was completely resected with wide surgical
      margins in combination with bilateral neck dissection. However, the patient
      developed pulmonary metastasis and died of respiratory failure 4 months after the
      final surgery. Postoperative inflammatory reaction followed by scar formation in
      the previously irradiated surgical site might have caused the transition from SCC
      to SpCC during the process of recurrence.

PMID- 18607934
TI  - Effects of eye position on the vestibular evoked myogenic potential.
AB  - CONCLUSION: The position of a subject's eyes during vestibular evoked myogenic
      potential (VEMP) recording significantly alters the magnitude of the response.
      This change is largely due to an alteration in the tonicity of the
      sternocleidomastoid muscle (SCM) caused by variations in the position of the eye.
      However, even if electromyographic (EMG) normalization is conducted effects of
      eye position remain. OBJECTIVE: To determine if eye position has a significant
      effect on the magnitude of the VEMP. SUBJECTS AND METHODS: VEMPs were collected
      from 32 ears measured on 16 healthy subjects. The recordings were made
      unilaterally using the head turn method. The acoustic stimuli were 500 Hz air
      conduction short tone bursts. VEMPs were measured in three recording conditions:
      (i) eyes in the same direction as head turn, (ii) eyes straight ahead, (iii) eyes
      in the opposite direction to head turn. RESULTS: All 32 ears tested showed a VEMP
      response with eyes in all three positions. Repeated measures analysis of variance
      (RM-ANOVA) verified an overall significant effect of eye position (p<0.001). Post
      hoc paired t tests revealed statistically significant differences between the
      eyes opposite and the other two conditions (p<0.001). Normalization of the VEMP
      magnitude using pre-stimulus EMG reduced the effect; however, some variability
      remained.

PMID- 18607936
TI  - Protective effect of edaravone against tobramycin-induced ototoxicity.
AB  - CONCLUSION: It is suggested that simultaneous treatment with the radical
      scavenger edaravone has an effective protective effect against tobramycin
      ototoxicity in rat. Even if the edaravone treatment is postponed for 7 days, it
      can still prevent hearing loss, but a 14 day delay cannot protect from
      ototoxicity. OBJECTIVES: With the aim of alleviating hearing loss caused by
      aminoglycoside ototoxicity, we performed a trial to assess the hearing protective
      efficacy of the radical scavenger edaravone. MATERIALS AND METHODS: In part one
      of the study, 21 male Sprague-Dawley albino rats were used; 2 rats served as
      controls for the safety of edaravone. Eight rats each received 10 subcutaneous
      injections (s.c.) of tobramycin (160 mg/kg b.w.) once daily and saline injection
      intraperitoneally for 2 weeks. Eleven rats were given 10 s.c. tobramycin
      injections simultaneously with an intraperitoneal injection of edaravone (3 mg/kg
      b.w.). In part two, tobramycin was injected in 13 rats (as above). Five of these
      received two edaravone injections 7 days later and four rats similarly 14 days
      later. Auditory brainstem response (ABR) was used to assess hearing. RESULTS: All
      rats treated only with tobramycin showed a deterioration of hearing. None of the
      rats given simultaneous treatment with tobramycin and edaravone demonstrated
      hearing loss. A 7 day delay in edaravone injection still prevented hearing loss,
      but a 14 day delay had only a temporary prophylactic effect.

PMID- 18607937
TI  - Analysis of long-term hearing after tympanosclerosis with total/partial
      stapedectomy and prosthesis used.
AB  - CONCLUSION: Long-term hearing gain results are good after prosthetic
      reconstruction of the stapes in the tympanosclerotic ear. The type of
      stapedectomy, whether partial or total, does not affect the result of the surgery
      very much. OBJECTIVES: Comparative evaluation of the hearing results of
      total/partial stapedectomy technique and the prosthesis used within a 10-year
      follow-up period after stapedectomy in cases with dense tympanosclerosis and
      completely fixed stapes. PATIENTS AND METHODS: Twenty-five cases with completely
      fixed stapes due to generalized tympanosclerosis were included in this
      retrospective study between 1995 and 2005. Two-stage canal wall up procedure was
      planned for all cases, and stapedectomy was performed at the second stage. After
      the second stage, 25 ears in the sixth month, 18 ears in the first year, 14 ears
      in the second year, and 7 ears in the tenth year were available for follow-up.
      Preoperative and postoperative air-bone gap values of the patients and their
      hearing gain were compared. Total stapedectomy was carried out in 17 of the
      patients and partial stapedectomy in 8 of them. For ossiculoplasty, a plastipore
      total ossicular replacement prosthesis was used in 17 patients, homograft ossicle
      in 2 patients, and Teflon piston in 6 patients. RESULTS: In 17 cases in which we
      used total stapedectomy, the average preoperative air-bone gap value improved
      from 40.23 to 18.47 in the sixth month, and from 38.4 dB to 9.6 dB in the tenth
      year. In eight cases in which we used partial stapedectomy, the average
      preoperative air-bone gap improved from 38.63 dB to 24.38 dB and from 35 dB to 17
      dB, respectively. The average postoperative hearing gain with total stapedectomy
      was 21.76 dB in the sixth month and 28.8 dB in the tenth year. Hearing gain with
      partial stapedectomy was successively 14.25 dB and 18 dB. When we compared the
      results of total prosthesis and Teflon pistons among the materials used in
      ossiculoplasty, although hearing gain with total prostheses was better, the
      results were not statistically significant.

PMID- 18607938
TI  - Activation of vocal fold healing with topical vitamin A in rabbits.
AB  - CONCLUSION: The results suggest that vitamin A can prevent scar formation in the
      vocal fold after surgery. OBJECTIVES: This study aimed to evaluate the effects of
      topically applied vitamin A on healing after vocal fold trauma. MATERIALS AND
      METHODS: Vocal folds of 20 adult rabbits were traumatized unilaterally. Ten of
      them were treated with topical application of vitamin A and the others served as
      controls. All animals were sacrificed after 10 days. Vocal folds were resected
      for analysis by light microscopy. RESULTS: The untreated vocal folds showed
      extensive deposition of collagen and fibroblast on light microscopy and vocal
      folds treated with vitamin A showed less deposition. There was a significant
      difference between the two groups according to the percentage of collagen and
      fibroblasts in the lamina propria (p<0.01).

PMID- 18607939
TI  - Experimental study on repair of the facial nerve with Schwann cells transfected
      with GDNF genes and PLGA conduits.
AB  - CONCLUSIONS: Schwann cells transfected by GDNF genes + PLGA were superior to
      Schwann cells + PLGA and direct anastomesis. This is a new and effective strategy
      for repair of facial nerve defects. OBJECTIVE: To evaluate the effect of
      bioactive artificial nerve conduits in the repair of facial nerve defects in
      Sprague-Dawley rats. MATERIALS AND METHODS: Schwann cells were harvested and
      transfected with PcDNA3.1 (+)/GDNF. After injection with Schwann cells, the
      conduits were cultured in the culture medium for 2 weeks. Thirty female Sprague
      Dawley rats were selected and randomly divided into three groups (A, B, and C),
      which were treated as follows: A, direct anastomesis; B, Schwann cells + PLGA
      conduits; C, Schwann cells transfected by GDNF genes + PLGA conduits. General
      observation, electrophysiological study, histological study, and image analysis
      were performed 2 weeks, 1 month, 2 months, and 3 months postoperatively. RESULTS:
      The recovery of nerve regeneration and electrophysiological results in group C
      were superior to those in groups A and B; the difference was statistically
      significant (p < 0.01).

PMID- 18607940
TI  - Facial nerve course in congenital aural atresia--identified by preoperative CT
      scanning and surgical findings.
AB  - CONCLUSIONS: The facial nerve courses shown by preoperative CT imaging coincide
      with the surgical findings in most congenital aural atresia cases. CT scanning is
      critical in evaluation of a patient's candidacy for atresia surgery. OBJECTIVES:
      To evaluate the diagnostic value of preoperative CT scanning of the facial nerve
      course in congenital aural atresia. SUBJECTS AND METHODS: All inpatients (135
      cases) with congenital aural atresia had routine preoperative CT examination. The
      facial nerve courses were observed in the operation and compared with the
      preoperative CT imaging. RESULTS: CT imaging showed that the mastoid portions of
      the facial nerves in 57% of cases (77/135) were located at the level of the round
      window, and 17% (23/135) were located at the levels of the oval window and the
      cochlea. Differential overlapping of the oval window by the facial nerve could
      also be shown in most of the cases. In the majority of cases (75%, 61/81) the
      tympanic portions of the facial nerve on CT imaging could be confirmed by
      surgical findings. In severe overlapping of the oval window or cases with
      anterior displacement, stapedectomy or tympanoplasty, respectively, could not be
      performed as usual.

PMID- 18607941
TI  - Predictive value of sentinel node biopsy in head and neck cancer.
AB  - CONCLUSIONS: The negative predictive value (NPV) of sentinel lymph node biopsy
      (SNB) in this study was 95%. The accuracy of SNB compared to histopathologic
      evaluation of surgical specimen of subsequent neck dissection (ND) was 96%.
      OBJECTIVE: To evaluate NPV of SNB in head and neck cancer. PATIENTS AND METHODS:
      This was a prospective clinical study comprising 35 patients (50 necks) with
      squamous cell carcinoma (SCC) of head and neck with clinically (cN0) and
      radiologically negative necks, without previous treatment, who underwent SNB with
      gamma probe and subsequent ND. The NPV, accuracy, sensitivity, and specificity of
      SNB were compared to histopathologic assessment of surgical specimens from NDs.
      Negative sentinel lymph nodes (SLNs) on histopathology were evaluated with step
      serial section (SSS) and immunohistochemistry (IHC). When a neck had a positive
      SLN, all lymph nodes of subsequent NDs were studied with SSS and IHC. RESULTS:
      There were primaries of the oral cavity (n=24), lip (n=3), oropharynx (n=3), and
      larynx (n=5). All patients had detected SLNs. In all, 41 necks were SLN-negative
      on histopathologic evaluation but 2 (5%) had metastases in non-SLNs after ND. Of
      these 41 necks, SLNs were level Ib (26%), IIa (45%), III (21%), and IV (8%). Nine
      necks presented positive SLN on histopathologic evaluation, level Ib (n=3), IIa
      (n=5), and III (n=2), and subsequent NDs were negative on conventional
      histopathologic analysis, but after SSS and IHC, two presented micrometastases.

PMID- 18607942
TI  - Expression of transient receptor potential vanilloid (TRPV) 1, 2, 3, and 4 in
      mouse inner ear.
AB  - CONCLUSION: It is suggested that transient receptor potential vanilloids (TRPVs)
      may play a functional role in cell physiology and TRPV-4 and -2 may play an
      important part in fluid homeostasis in the inner ear. OBJECTIVE: Expression of
      TRPV-1, -2, -3, and -4 in the normal mouse inner ear was studied. MATERIALS AND
      METHODS: CBA/J mice were used in this study. The localization of TRPV-1, -2, -3,
      and -4 in the inner ear, i.e. cochlea, vestibular end organs, and endolymphatic
      sac, was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were
      co-expressed in hair cells and supporting cells of the organ of Corti, in spiral
      ganglion cells, sensory cells in vestibular end organs, vestibular ganglion
      cells, and sensory nerve fibers. TRPV-2 was also detected in the stria
      vascularis, dark cells, and endolymphatic sac. TRPV-4 was expressed in hair cells
      and supporting cells of the organ of Corti, in marginal cells of the stria
      vascularis, spiral ganglion cells, vestibular sensory cells, vestibular dark
      cells, vestibular ganglion cells, and epithelial cells of the endolymphatic sac.

PMID- 18607943
TI  - The results of vestibular evoked myogenic potentials, with consideration of age
      related changes, in vestibular neuritis, benign paroxysmal positional vertigo,
      and Meniere's disease.
AB  - CONCLUSION: We interpreted VEMP findings in patients with the three major
      peripheral vertigo diseases, taking age-related changes into consideration. We
      found different abnormal VEMP rates among the three diseases, as well as
      differences in the proportion of parameters that were abnormal, according to the
      type of disease. OBJECTIVES: Vestibular neuritis, benign paroxysmal positional
      vertigo (BPPV), and Meniere's disease, common diseases that cause peripheral
      vertigo, often affect the saccule or inferior vestibular nerve, which are
      pathways of vestibular evoked myogenic potential (VEMP). Also, aging could have a
      primary effect on diminished VEMP responses. Our study investigated VEMP the
      findings in patients with the diseases in relation to their age. PATIENTS AND
      METHODS: A total of 134 patients with vestibular neuritis, 62 with BPPV, and 29
      with Meniere's disease were enrolled in this study. The VEMP findings in patients
      within the three disease groups were interpreted using our own normative ranges
      according to age. RESULTS: Abnormal VEMP rates in the vestibular neuritis, BPPV,
      and Meniere's disease groups were 36.6%, 25.8%, and 69%, respectively. The
      proportion of prolonged p13 latency in BPPV patients with abnormal VEMP responses
      was relatively high compared with the other two diseases. VEMP asymmetry in the
      patients with Meniere's disease was relatively high.

PMID- 18607945
TI  - Vestibular drop attack secondary to Meniere's disease results from unstable
      otolithic function.
AB  - CONCLUSION: The otolithic organs of patients with vestibular drop attack (VDA)
      secondary to Meniere's disease were damaged but the damage was not complete. In
      other words, the otolithic functions of patients with VDA were unstable.
      OBJECTIVE: To evaluate otolithic function using vestibular evoked myogenic
      potential (VEMP) in patients with VDA secondary to Meniere's disease. PATIENTS
      AND METHODS: Clinical records of three patients with VDA secondary to Meniere's
      disease were reviewed with special reference to VEMP testing. RESULTS: The three
      patients were classified as stage II or III Meniere's disease. A long-term follow
      up of VEMP in two patients showed reversible changes of VEMP reflexes, and VEMP
      testing with glycerol administration in two patients revealed the recovery of
      VEMP responses after taking glycerol, and the existence of saccular endolymphatic
      hydrops.

PMID- 18607946
TI  - Event-related potentials in patients with olfactory loss.
AB  - CONCLUSION: The olfactory event-related potential (OERP) method provides a means
      of objectively assessing olfactory function. However, further validation is
      needed before OERPs can be routinely applied in clinical assessment of olfactory
      dysfunction. OBJECTIVE: To assess OERPs in patients with olfactory impairment and
      in healthy controls to investigate possible dose-response effects of odor
      concentration on OERP parameters in these groups, thereby exploring possibilities
      and limitations regarding the clinical utility of the OERP method. SUBJECTS AND
      METHODS: Twenty-three patients with a history of impaired olfactory function and
      24 controls participated in the study. Olfactory function was assessed with
      psychophysical tests, i.e. assessment of the odor threshold, and odor
      identification. OERPs were obtained in response to the olfactory stimulant
      butanol at two different concentrations, presented via an olfactometer. RESULTS:
      The OERP amplitudes increased and the latencies shortened with increasing
      stimulus concentration. Furthermore, a difference between the groups was found,
      with higher OERP amplitudes and shorter latencies in healthy subjects compared
      with patients.

PMID- 18607947
TI  - Efficacy of total intravenous anesthesia without intubation for laryngeal
      framework surgery.
AB  - CONCLUSION: Total intravenous anesthesia (TIVA) without intubation has the
      advantages of both conventional general anesthesia and local anesthesia. It is
      useful in laryngeal framework surgery because intraoperative voice monitoring
      while the patient remains awake is required. OBJECTIVE: In laryngeal framework
      surgery, it is desirable to monitor the voice during surgery. However, surgery is
      conducted under general anesthesia, although such a procedure renders the patient
      unable to phonate during surgery. We conducted TIVA without intubation, allowing
      patients to breathe spontaneously while undergoing operation, and succeeded in
      intraoperative voice monitoring with satisfactory postoperative voice production.
      SUBJECTS AND METHODS: The subjects were 21 patients who underwent surgery. For
      TIVA, propofol and pentazocine were used as a sedative and analgesic,
      respectively. A bispectral index (BIS) monitor was used to measure the depth of
      the anesthesia. Before the vocal folds were to be rotated, propofol
      administration was interrupted to arouse and instruct the patient to phonate.
      Guided by the phonation, the vocal folds were correctly positioned. Then propofol
      administration was resumed, and the wound was closed. RESULTS: The BIS value
      during continued administration of propofol was around 60, but exceeded 90 in all
      patients within 233.6 +/- 64.5 s after cessation. They clearly remembered the
      conversation they had with us during surgery.

PMID- 18607948
TI  - Electrophysiological effects of electrode pull-back in cochlear implant surgery.
AB  - CONCLUSION: The surgical technique of electrode pull-back had a significant
      improving effect on the spread of excitation (SOE). However, the long-term
      clinical and audiological outcome of this modified surgical technique should be a
      subject of further studies. OBJECTIVE: To observe the intraoperative
      electrophysiological effects of a surgical electrode insertion technique (i.e.
      pull-back) in cochlear implantation. PATIENTS AND METHODS: The influence of the
      pull-back technique on intraoperatively recorded electrophysiological parameters
      (including T-NRT, ECAP amplitude, SOE) was investigated in a prospective, non
      randomized, intraoperative study. In addition, we observed the correlation of
      insertion depth and SOE differences after a controlled electrode pull-back. We
      implanted 13 patients (aged 18-76 years) with a Nucleus 24CI RE cochlear implant
      with a perimodiolar electrode. RESULTS: After a controlled pull-back, a
      significant decrease of the SOE at different electrodes (upon recording from
      electrodes 5, 10, 15) was observed. Electrode 10 was the SOE area with the most
      significant and homogeneous changes after pull-back. The change in the ECAP
      amplitudes was highly variable in correlation with the changes in the SOE.

PMID- 18607950
TI  - Non-sentinel node tumor invasion in oropharyngeal and oral cancer: risk of
      misdiagnosis of metastasis.
AB  - CONCLUSION: The existence of patients with positive non-sentinel node indicates a
      risk of misdiagnosis of metastasis in oropharyngeal and oral cancer. OBJECTIVES:
      We attempted to confirm the usefulness of sentinel lymph node biopsy (SLNB) in
      oropharyngeal and oral cavity cancer to detect clinically occult metastases.
      PATIENTS AND METHODS: Twenty-two patients with a mean age of 57 (SD=13) years
      were studied prospectively. All presented T1-T3 squamous cell carcinoma (SCC) of
      the oropharynx or oral cavity, and were cN0 on palpation and CT. A preoperative
      (24 h) lymphoscintigraphy was performed with 99mTc-labelled sulfur colloid
      injected around the primary tumor. Subsequently, we proceeded with tumor exeresis
      and detection of SLN following the procedures described in a previous paper.
      RESULTS: We detected a total of 32 SLNs in 21 of 22 patients. Ipsilateral neck
      node location was observed in 18 patients and bilateral in 3. We observed 10
      patients with true positive SLNs (3 patients had micrometastases), indicating
      occult metastases. We harvested a total of 454 nodes in our selective neck
      dissections, 19 of which presented metastatic invasion. We identified four
      patients with positive non-sentinel nodes.

PMID- 18607951
TI  - Hyperbaric oxygen therapy seems to enhance recovery from acute acoustic trauma.
AB  - CONCLUSION: The average recovery of hearing and cessation of tinnitus was
      significantly better after hyperbaric oxygen therapy (HBOT) than after normobaric
      oxygen therapy (NBOT). HBOT can be valuable adjuvant therapy for patients with
      acute acoustic trauma (AAT). OBJECTIVES: AAT was one of the early indications for
      the use of HBOT. The rationale of administering oxygen to patients with AAT is
      based on experimental studies showing that noise exposure results in cochlear
      hypoxia, which could be compensated by HBOT. The aim of this study was to
      investigate the efficacy of HBOT in patients with AAT. PATIENTS AND METHODS: We
      compared the recovery from hearing impairment and tinnitus in 60 ears treated
      with HBOT with 60 ears treated with NBOT. The HBOT was given daily for 1-8 days.
      There were no significant differences in clinical or audiological data between
      HBOT and NBOT groups. RESULTS: The average recovery of hearing both at high and
      speech frequencies was significantly better and tinnitus persisted less commonly
      after the HBOT than after the NBOT. Normal hearing at the end of the follow-up
      period was regained in 42 ears in the HBOT group and in 24 ears in the NBOT group
      (p<0.01).

PMID- 18607952
TI  - p53, epidermal growth factor receptor and proliferating cell nuclear antigen in
      laryngeal squamous cell carcinoma are not predictive markers for the effect of
      adjuvant radiotherapy.
AB  - CONCLUSION: These data indicate that the expression of p53, epidermal growth
      factor receptor (EGFR) or proliferating cell nuclear antigen (PCNA) is not a
      reliable predictor of the prognosis or the effect of adjuvant radiotherapy in
      patients with laryngeal squamous cell carcinoma (LSCC). OBJECTIVE: The aim of
      this study was to investigate the prognostic significance of p53, EGFR, and PCNA
      in LSCC and to assess the relationships between the expression of these molecular
      markers and the effect of adjuvant radiotherapy. PATIENTS AND METHODS: We
      retrospectively reviewed the expression of these molecular markers in 75 patients
      with LSCC. RESULTS: None of the expressions of these molecular markers was
      associated with disease-free survival or overall survival and no significant
      correlations were found between them and the effect of adjuvant radiotherapy.
      Also, they were not associated with each other.

PMID- 18607953
TI  - Natural history of contralateral residual hearing in binaural-bimodal hearing.
AB  - CONCLUSIONS: The range of evaluation tools used in deciding which ear to implant
      and which to designate for a hearing aid (HA) should be expanded to include
      additional aspects to those tested by audiometry and basic speech perception.
      Residual hearing in non-implanted ears remains stable for at least 3 years after
      unilateral cochlear implantation, but regular refitting and monitoring of the HA
      function combined with cochlear implant (CI) mapping are mandatory for maximizing
      benefit from binaural-bimodal hearing. OBJECTIVES: To examine whether the
      clinical decision-making tools currently used to assess hearing are reliable
      guides when choosing the preferred ear for CI, and to determine the rate of
      residual hearing deterioration in the non-implanted ear over 36 months post-CI as
      a guide to recommending subsequent continued use of a contralateral HA as opposed
      to CI. PATIENTS AND METHODS: This was a retrospective evaluation of patients'
      charts. The pre-CI choice of the ear for implantation in a group of 37 binaural
      bimodal users was re-evaluated. In a second group of 22 patients, residual
      hearing deterioration was followed for 36 months post-implantation. RESULTS: In
      the group of 37 patients, subjective identification of the worse-hearing ear was
      in agreement with audiometric results in 28 cases, but disagreed with the unaided
      audiometric results in the other 9. Mean threshold values for the group of 22
      patients remained stable over 36 months post-CI, except for the aided threshold
      at 4.0 kHz, which deteriorated by 10.9 dB (p=0.003).

PMID- 18607954
TI  - Inhibitory effect of caffeic acid phenethyl ester (CAPE) on LPS-induced
      inflammation of human middle ear epithelial cells.
AB  - CONCLUSIONS: The results suggest that the anti-inflammatory effect of caffeic
      acid phenethyl ester (CAPE) is due to its inhibition of tumor necrosis factor
      (TNF)-alpha expression and interleukin (IL)-8 production. The anti-inflammatory
      effect of CAPE is possibly through the inhibition of nuclear factor (NF)-kappaB
      via the suppression of inhibitor-kappaB-alpha (IkappaB-alpha) degradation.
      OBJECTIVES: CAPE is a biologically active component of propolis, a resinous
      material obtained from bee hives, which originates from conifer bark. The effect
      of CAPE on lipopolysaccharide (LPS)-induced inflammatory reactions is not known.
      The aim of this study was to evaluate the anti-inflammatory effect of CAPE on
      cultured human middle ear epithelial cells (HMEECs). MATERIALS AND METHODS: The
      effect of CAPE on LPS-induced TNF-alpha expression was evaluated in HMEECs by
      real-time reverse transcription polymerase chain reaction (RT-PCR). LPS-induced
      IL-8 production was determined by enzyme-linked immunosorbent assay (ELISA), and
      LPS-induced IkappaB-alpha degradation was followed by Western blot analysis.
      RESULTS: CAPE significantly inhibited LPS-induced up-regulation of TNF-alpha in a
      dose-dependent manner. IL-8 production by LPS was significantly suppressed by the
      CAPE pretreatment. Furthermore, LPS-induced IkappaB-alpha degradation was
      suppressed by the CAPE pretreatment.

PMID- 18607955
TI  - An approach to managing non-melanoma skin cancer of the nose with mucosal
      invasion: our experience.
AB  - CONCLUSIONS: The absence of recurrences after final nasal reconstruction
      demonstrates the reliability of our three-stage strategy and the necessity to
      delay nasal reconstruction, focusing attention on oncological safety for nasal
      non-melanoma skin cancer (NMSC) with mucosal invasion. OBJECTIVES: To validate a
      therapeutic strategy aimed at oncological safety and minimization of possible
      recurrences after full-thickness excision of nasal NMSC with mucosal invasion.
      The strategy was divided into three stages: surgical excision with clinically
      safe perilesional skin margins and extemporary frozen section histological
      control; 8-15 months follow-up leaving the nasal defect unreconstructed with a
      'wait and see' strategy; new extemporary histological control of defect margins
      and, if negative, definitive reconstruction. PATIENTS AND METHODS: Twenty
      patients affected by nasal NMSC with mucosal invasion were treated and followed
      up. RESULTS: Basal cell carcinoma was the most common lesion (75%), followed by
      squamous cell carcinoma (25%). Ultrasonography excluded lymphatic involvement for
      SCC. Before final reconstruction, extemporary histological examination revealed
      the presence of tumour cells in three patients. After tumour extirpation, these
      patients were resubmitted to a new follow-up period before reconstruction. No
      recurrences were observed after definitive nasal reconstruction in all patients
      during the 5-year follow-up.

PMID- 18607957
TI  - A new treatment for snoring: sling snoreplasty with a permanent thread.
AB  - CONCLUSION: Sling snoreplasty could be a new effective palatal snoring procedure
      with minimal side effects. It could be combined with other snoring and sleep
      apnea operations. OBJECTIVES: To introduce sling snoreplasty with a permanent
      thread. PATIENTS AND METHODS: The procedure is performed under local anesthesia
      and in the sitting position. The instrument requirements include a nylon no. 4
      suture, two needle-holders (or one needle-holder and a straight kelly), and a
      tongue depressor. Sling snoreplasty with a permanent thread is a retention suture
      technique applied to three portions of redundant soft palate in a triangular,
      tetragonal or pentagonal shape. RESULTS: Sling snoreplasty could be called a
      three-dimensional retention suture technique to shorten, conglomerate, and tense
      the soft palate. It also elevates the soft palate forward and upward, and widens
      the oral cavity and nasopharyngeal space. The suture not only provides a sling
      effect in the soft palate but also incorporates into the soft palate musculature,
      imparting rigidity to the airway like tongue suspension suture. Patients have
      only a little pain and normal diet on the day after surgery. There are minimal
      postoperative complications.

PMID- 18607956
TI  - Changes in transient receptor potential vanilloid (TRPV) 1, 2, 3 and 4 expression
      in mouse inner ear following gentamicin challenge.
AB  - CONCLUSION: It is suggested that transient receptor potential vanilloid (TRPV)-1
      and -2 may be of pathological significance for sensory cells and ganglions, while
      TRPV-3 and -4 may play an important part in neuroprotection of the inner ear.
      OBJECTIVE: Changes in the expression of TRPV-1, -2, -3, and -4 in gentamicin (GM)
      treated mouse inner ear were studied. MATERIALS AND METHODS: CBA/J mice were used
      in this study. The localization of TRPV-1, -2, -3, and -4 in the inner ear of
      both untreated and GM-treated CBA/J animals (intratympanic injection of 5 mg GM)
      was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were co
      expressed in the inner ear sensory and ganglion cells, while TRPV-4 was also
      expressed in the stria vascularis and vestibular dark cells. Following GM
      treatment, the intensity of immunofluorescent reaction to TRPV-1 and TRPV-2
      increased, while that to TRPV-3 and TRPV-4 decreased.

PMID- 18607958
TI  - Head and neck cancer in renal transplant patients in Finland.
AB  - CONCLUSIONS: This study found a 0.8% incidence of non-cutaneous head and neck
      cancer during a mean follow-up of 10 years. The benefits of successful renal
      transplantation clearly outweigh the observed risk of malignancy. OBJECTIVE:
      Increased cancer incidence after organ transplantation is well documented but few
      studies have reported on the rate of head and neck malignancies among these
      patients. This study aimed to determine the incidence and specific sites of head
      and neck cancer in a nationwide series of renal transplant patients in Finland.
      PATIENTS AND METHODS: Data from the National Kidney Transplant Registry and the
      Finnish Cancer Registry were used. A total of 2884 kidney transplant patients
      from the period 1964 to 1997 were followed for cancer incidence during the period
      from 1967 to 2003. RESULTS: There were 113 non-lymphomatous head and neck
      malignancies. The standardized incidence ratio (SIR), as compared with the
      general population, was 13.6, with a 95% confidence interval (CI) of 11.2-16.2.
      The SIR was significantly elevated for cancers of the skin (47.3, 95% CI 36.3
      60.7), lip (31.8, 95% CI 20.8-46.6), oral cavity (6.5, 95% CI 2.4-14.0) and
      thyroid (5.8, 95% CI 3.0-10.2).

PMID- 18607959
TI  - Expression and immunolocalization of aquaporin-6 (Aqp6) in the rat inner ear.
AB  - CONCLUSION: Since aquaporin-6 (Aqp6) protein was located in the membrane of
      intracellular vesicles of the stria vascularis, endolymphatic sac, and vestibule,
      Aqp6 might be involved in some distinct physiological function of acid-base
      metabolism and water balance in endolymphatic fluid homeostasis. However, its
      lack of expression on the plasma membrane indicates that Aqp6 does not have a
      direct role in water flux via the plasma membrane. OBJECTIVE: To evaluate the
      expression and immunolocalization of Aqp6 in the rat inner ear. MATERIALS AND
      METHODS: Wistar rats were used. Aqp6 mRNA expression in the rat inner ear was
      investigated in the vestibulum as well as in the cochlea and endolymphatic sac
      using the reverse transcription-polymerase chain reaction (RT-PCR) method, and
      detailed immunolocalization of Aqp6 in the rat inner ear was investigated using
      immunohistochemical methods including immunofluorescence microscopy and
      immunoelectron microscopy. RESULTS: We obtained novel data showing that not just
      Aqp6 mRNA but also Aqp6 protein is expressed in the cochlea, endolymphatic sac,
      and vestibule. Immunoelectron microscopic studies revealed that the
      immunolabelled gold was diffusely seen in the intracellular area of the stria
      vascularis, endolymphatic sac, and vestibule, but never in the plasma membranes.

PMID- 18607960
TI  - Effect of resection of the posterior nasal nerve on functional and morphological
      changes in the inferior turbinate mucosa.
AB  - CONCLUSIONS: The underlying pathophysiological mechanisms of the posterior nasal
      nerve (PNN) resection involved the suppression of the secretogogue motor and the
      inhibition of neurogenic inflammation induced by parasympathetic and sensory
      denervation. OBJECTIVE: The study was designed to clarify the underlying
      mechanisms of the resection of the PNN. PATIENTS AND METHODS: Ten patients with
      allergic rhinitis and non-allergic chronic rhinitis were enrolled in the study.
      Clinical symptoms were evaluated before and after administration of oxitropium
      bromide aerosol, and after the PNN resection. Biopsy specimens from the inferior
      turbinate mucosa obtained from five patients before and after resection of the
      PNN were examined. RESULTS: The application of oxitropium bromide resulted in a
      significant reduction of both watery rhinorrhea and nasal obstruction, but not
      sneezing or postnasal drip. Resection of the PNN also significantly improved both
      rhinorrhea and nasal obstruction. Morphometric analysis of the density of the
      nasal gland showed a significant reduction, whereas no significant change was
      recognized in the density of the vessels. A significant reduction in the number
      of infiltrating neutrophils, eosinophils, and lymphocytes was recognized.

PMID- 18607961
TI  - Possible prognostic role of p53 expression in laryngeal squamous cell carcinoma
      of non-smokers, non-alcoholic patients.
AB  - CONCLUSIONS: p53 expression seems to negatively influence survival in non-smoking
      non-alcoholic patients with squamous cell laryngeal carcinoma. p53 might be
      implicated in the oncogenic pathways leading to neoplastic transformation in this
      population of patients. OBJECTIVES: The aim of this study was to analyze the
      prognostic significance of p53 immunohistochemical expression in laryngeal
      squamous cell carcinoma arising in non-smoking non-alcoholic patients. PATIENTS
      AND METHODS: We retrospectively reviewed the data from 782 patients diagnosed
      with laryngeal squamous cell carcinoma in the last 15 years at Mostoles Hospital.
      From these patients we chose 21 who had never smoked or drunk alcohol and
      performed immunohistochemical staining for p53 protein in paraffin-embedded
      archival blocks. RESULTS: We demonstrated immunohistochemical positivity for p53
      in the samples from eight patients, most of them with a focal and weak pattern
      (<25% positivity in six cases). p53 expression did not show any significant
      prognostic influence on the risk of local or regional recurrence of the tumor,
      but significantly influenced the risk of death (log-rank test, p=0.03).

PMID- 18607962
TI  - Reorganization of sleep architecture after surgery for OSAHS.
AB  - CONCLUSION: Genioglossus advancement and hyoid suspension (GAHM) plus
      uvulopalatopharyngoplasty (UPPP) can decrease the apnea hypopnea index (AHI) and
      arousal index, especially respiratory-related arousals. Correspondingly, sleep
      architecture is reorganized, which is expressed postoperatively as an increase in
      slow wave sleep and a decrease in lighter sleep. OBJECTIVE: To explore the
      reorganization of sleep patterns after GAHM plus UPPP for severe obstructive
      sleep apnea hypopnea syndrome (OSAHS). PATIENTS AND METHODS: GAHM plus UPPP was
      performed on 31 patients with severe OSAHS (AHI > 40). The postoperative follow
      up was 6 months. RESULTS: The AHI was reduced from 65.93 +/- 23.83 preoperatively
      to 28.58 +/- 29.11 postoperatively. The arousal index was reduced from 56.00 +/-
      18.78 to 41.97 +/- 20.73, and the respiratory arousal index was reduced from
      35.44 +/- 21.57 to 22.63 +/- 21.99. No significant change was seen in the
      spontaneous arousal index (preoperative, 20.56 +/- 12.97; postoperative, 19.34 +/
      10.29). The percentage of REM sleep during the total sleep time (TST) increased
      from 10.53 +/- 9.13% to 13.92 +/- 6.76%, and the S3 + S4 percentage of TST
      increased from 3.07 +/- 3.01% to 7.09 +/- 6.83%. Correspondingly, the S1 + S2
      percentage of TST decreased from 86.53 +/- 9.28% to 78.89 8.89%.

PMID- 18607963
TI  - Intratympanic gentamicin therapy for control of vertigo in unilateral Menire's
      disease: a prospective, double-blind, randomized, placebo-controlled trial.
AB  - CONCLUSIONS: Intratympanic application of gentamicin is a relatively safe and
      efficient treatment for the reduction of complaints of vertigo attacks associated
      with Meniere's disease. The treatment also reduces the severity of the perceived
      aural fullness. OBJECTIVE: To investigate the effectiveness of intratympanic
      gentamicin treatment in patients with unilateral Meniere's disease. SUBJECTS AND
      METHODS: In a prospective, double-blind, randomized, placebo-controlled clinical
      trial subjects scored vertigo complaints, aural fullness and tinnitus, before,
      during and up to 1 year after treatment. Hearing loss was monitored with pure
      tone audiometry. RESULTS: Gentamicin treatment resulted in a significant
      reduction of the score for vertigo complaints and the score for perceived aural
      fullness. A small increase in hearing loss (average 8 dB) was measured in the
      gentamicin group.

PMID- 18607964
TI  - Effect of water-soluble coenzyme Q10 on noise-induced hearing loss in guinea
      pigs.
AB  - CONCLUSION: The results of this study indicate that coenzyme Q10 reduces cochlear
      oxidative stress induced by acoustic overstimulation. OBJECTIVE: We investigated
      the effects of coenzyme Q10 on noise-induced hearing loss in guinea pigs.
      MATERIALS AND METHODS: Animals received water-soluble coenzyme Q10
      intraperitoneally 2 h before noise exposure. Seven days after noise exposure (130
      dB sound pressure level for 3 h), the auditory brainstem response (ABR) threshold
      shift and cochlear hair cell damage were assessed. RESULTS: We observed that the
      ABR threshold shift was significantly less in the coenzyme Q10 group than in the
      vehicle control group. In addition, the percentage of missing outer hair cells
      was lower in the coenzyme Q10 group than in the control group. Moreover, 2 days
      after administration of coenzyme Q10, increased antioxidative activity in the
      cochlea, as measured by analysis of hydroxy radical scavenging activity by
      electron spin resonance was observed.

PMID- 18607966
TI  - The formation of sinus in congenital stenosis of external auditory canal with
      cholesteatoma.
AB  - CONCLUSIONS: In congenital stenosis of the external auditory canal (CSEAC) with
      cholesteatoma, the bony wall of the external auditory canal (EAC) is most
      commonly involved. This involvement will lead to bone erosion of the EAC and may
      subsequently lead to the formation of postaural or cervical sinuses. High
      resolution computed tomography (HRCT) of temporal bone can show characteristic
      signs of soft tissue mass in EAC, with adjacent bone erosion. OBJECTIVE: To
      investigate the clinical features, differential diagnosis and management of CSEAC
      with cholesteatoma. PATIENTS AND METHODS: The clinical information for 10 cases
      of CSEAC with cholesteatoma was retrospectively reviewed. RESULTS: The patients'
      ages ranged from 4.75 to 22 years (average 12 years). The diameter of EACs was <
      2 mm. All 10 ears had a history of postaural fistulae or sinuses. Bone erosion of
      EAC was distinctly shown in HRCT of all cases, as well as soft tissue masses,
      which led to enlargement of the bony canals. All patients underwent canaloplasty;
      eight ears received hearing reconstructions at the same time. Cholesteatoma in
      EACs was confirmed during the operations, accompanied by compression and
      destruction of the post-superior and/or inferior bony wall. Postoperative
      pathologic examinations proved the diagnosis of cholesteatoma, and excluded any
      tissue of bronchial cleft cyst or fistula. After a follow-up of 1-3 years, no
      recurrent cholesteatoma was found in any of the 10 cases. All reconstructed EACs
      were clean and smooth. The hearing levels in the eight ears that received hearing
      reconstructions increased 20-35 dBHL.

PMID- 18607969
TI  - Functional outcome of retrosigmoid approach in vestibular schwannoma surgery.
AB  - CONCLUSION: The retrosigmoid approach for small vestibular schwannomas (VS)
      yields a high rate of facial function preservation. Hearing preservation rates
      depend on tumor size and preoperative hearing. OBJECTIVES: To report the results
      and to investigate the prognostic factors for hearing preservation after removal
      of small VS by a retrosigmoid approach. PATIENTS AND METHODS: From October 1994
      to July 2005, 110 VS removed through a retrosigmoid approach were included in
      this retrospective study. Preoperative and postoperative clinical, audiometric,
      videonystagmographic, and imaging data were collected. The mean follow-up period
      was 23+/-20.7 months (range 1-110). RESULTS: The preservation of a good facial
      function (House and Brackmann grade 1-2) was achieved in 91% of patients at 1-2
      years after surgery. Among patients with a preoperative class A or B (n=99), a
      postoperative serviceable hearing (AAO-HNS classes A and B) was preserved in 36%
      and a useful hearing (classes A, B, and C) in 44%. Hearing preservation appeared
      to be influenced by tumor size and preoperative hearing. Multiple regression
      analysis of the preoperative factors influencing the hearing outcome showed that
      preoperative high frequency pure tone thresholds associated with tumor size were
      better correlated to postoperative pure tone average (PTA) than preoperative low
      frequencies.

PMID- 18607970
TI  - Comparison of vestibular function between large cerebellopontine angle meningioma
      and schwannoma.
AB  - CONCLUSION: Abnormal caloric and vestibular evoked myogenic potential (VEMP)
      responses are frequently encountered with a large cerebellopontine angle (CPA)
      schwannoma, while normal caloric responses and abnormal VEMPs are noted with a
      large CPA meningioma. This difference may possibly exist because schwannoma
      causes vestibular deficits via parenchymal involvement, while vestibular deficits
      in the meningioma are mostly due to compression neuropathy. OBJECTIVES: This
      study aimed to compare the tumor characteristics in relation to vestibular
      function, i.e. caloric and VEMP responses, between large-sized (>2.5 cm)
      meningioma and schwannoma in the CPA. PATIENTS AND METHODS: Five patients with
      large CPA meningioma and nine patients with large CPA schwannoma were enrolled in
      this study. Each patient underwent a battery of tests including audiometry,
      caloric test, VEMP test, and MRI study. RESULTS: The meningioma group showed 20%
      caloric abnormality and 75% VEMP abnormality, while the schwannoma group revealed
      100% caloric and 100% VEMP abnormalities. A significant difference existed in
      relation to caloric abnormality between the two groups, but not in relation to
      VEMP abnormality.

PMID- 18607967
TI  - Effect of inner ear blood flow changes on the endolymphatic sac.
AB  - CONCLUSIONS: That the endolymphatic sac (ES) reacts to changes in inner ear blood
      flow may be important for homeostasis of the inner ear fluid volume and pressure.
      OBJECTIVES: To elucidate the effect of changes in inner ear blood flow on the ES
      and to learn more about the volume and pressure regulatory function of the ES.
      MATERIALS AND METHODS: Epinephrine or sodium nitroprusside (SNP) was injected
      into the middle ear cavity of adult CBA/J mice. The ES were analyzed
      morphologically by light microscopy. RESULTS: Epinephrine reduced the luminal
      size of the ES leading to an accumulation of intraluminal homogeneous substance.
      Injection of SNP increased the size of the ES lumen, accompanied by a collapse of
      the lateral intercellular space (LIS) and dense perisaccular tissue. These
      changes were almost reversed 4 h after injection.

PMID- 18607972
TI  - Ototoxic interaction of kanamycin and 3-nitropropionic acid.
AB  - CONCLUSION: Mitochondrial dysfunction in the cochlea potentiates the ototoxicity
      of aminoglycosides. OBJECTIVE: This study examined whether mitochondrial
      dysfunction in the cochlea affects the ototoxicity of aminoglycosides. MATERIALS
      AND METHODS: Nineteen guinea pigs were treated with the mitochondrial toxin 3
      nitropropionic acid (3-NP), kanamycin, both agents, or normal saline as control.
      After 14 days, hair cell loss and auditory brainstem response (ABR) were
      assessed. RESULTS: The administration of 400 mg/kg of kanamycin caused neither
      hair cell loss nor ABR threshold shift. Administration of 3-NP caused mild ABR
      threshold shift without significant hair cell loss. Administration of 3-NP and
      kanamycin caused ABR threshold shift and significant hair cell loss.

PMID- 18607971
TI  - Centrosome abnormalities in head and neck squamous cell carcinoma (HNSCC).
AB  - CONCLUSIONS: Numerical and structural centrosome abnormalities play a critical
      role in the tumor progression of in head and neck squamous cell carcinoma (HNSCC)
      and may provide useful information as a prognostic factor for these patients.
      OBJECTIVES: Centrosome alterations are often linked with aneuploidy, cell
      transformation, and tumor progress. We investigated centrosome abnormalities in
      HNSCC and correlated these variables to clinicopathological parameters and
      clinical follow up data of the patients. METHODS: Retrospective analysis of
      numerical and structural alterations of centrosomes in tumor tissues and
      corresponding normal epithelium (n=50 and 31, respectively). Immunohistochemistry
      was performed using an anti-gamma-tubulin antibody. Image acquisition was done by
      an Orthoplan microscope, centrosomes were segmented interactively, and area as
      well as mean optical density was measured. Aneuploidy was evaluated by
      fluorescence in situ hybridization in a subset of cases (n=29). RESULTS:
      Numerical and structural centrosome abnormalities differed significantly between
      normal squamous epithelium and tumor cells (both P<0.0001). Especially numerical
      centrosome abnormalities were significantly associated with T category and tumor
      stage (both P<0.0001) and the occurrence of distant metastasis (P=0.002 and
      P=0.019, respectively). Numerical centrosome abnormalities correlated also with
      disease free survival of the patients (P=0.032) as well as shorter overall
      survival (P=0.003).

PMID- 18607973
TI  - Motorized head impulse rotator in patients with vestibular schwannoma.
AB  - CONCLUSION: Motorized head impulse rotator is an effective technique to assess
      peripheral vestibular function. Approximately a quarter of patients with
      vestibular schwannoma (VS) had preserved preoperative responses. Vestibular
      disability could not be predicted based on vestibulo-ocular reflex (VOR)
      performance during motion stimuli, or in the caloric test. OBJECTIVES: To explore
      motorized head impulse rotator for evaluation of angular horizontal VOR in
      patients with VS, and to compare these responses to those of the caloric test and
      the symptoms. PATIENTS AND METHODS: We prospectively recorded head and eye
      position during unpredictable motorized head impulses in 38 patients with VS. We
      calculated gain and asymmetry of VOR (mean +/- 95% CI), and the results were
      compared to those of the caloric test and a questionnaire regarding dizziness,
      hearing and quality of life. RESULTS: The VOR during motorized impulses was
      abnormal in 71% of patients. Asymmetry in gain correlated significantly (p <
      0.001) with unilateral weakness in the caloric test. Preoperative gain was
      significantly lowered to 0.83 +/- 0.08 on the ipsilateral side compared to 0.98
      +/- 0.06 on the contralateral side. Postoperative gain on the operated side of
      0.53 +/- 0.05 was significantly different from preoperative gain (p < 0.001).
      Findings in vestibular tests did not correlate with subjective sensation of
      dizziness.

PMID- 18607974
TI  - Detection of respiratory viruses in nasopharyngeal secretions and middle ear
      fluid from children with acute otitis media.
AB  - CONCLUSIONS: Our results suggest that various respiratory viruses contribute to
      the pathogenesis of acute otitis media (AOM). OBJECTIVE: AOM is one of the most
      common complications of viral upper respiratory tract infections in children.
      Recently, the importance of respiratory viruses has been stressed as causative
      agents of AOM. SUBJECTS AND METHODS: A total of 1092 children < or =10 years old
      (average age 1.38 years) diagnosed as having AOM between 2002 and 2004 were
      studied. Bacterial and viral cultures of both nasopharyngeal secretions (NPS) and
      middle ear fluid (MEF) were performed for all 1092 children. Body temperature,
      changes of the tympanic membrane, and the number of days from the onset of
      illness were analyzed. RESULTS: Respiratory viruses were detected in 360 of 1092
      NPS specimens, including 157 isolates of respiratory syncytial virus and 88 of
      influenza virus. Among 1092 MEF specimens, 102 were virus-positive, including 43
      for respiratory syncytial virus and 29 for influenza virus. In 75 children,
      respiratory viruses were only detected in MEF. The viral detection rate was
      higher in children with fever at an early stage of their illness. The tympanic
      membrane changes associated with viral infection tended to be less severe, while
      changes were more severe in cases with bacterial infection, especially co
      infection with bacteria and viruses.

PMID- 18607975
TI  - Comparison of radiotherapy strategies for locally advanced hypopharyngeal cancer
      after resection and ileocolic flap reconstruction.
AB  - CONCLUSION: IMRT provided better conformity, less toxicity and better function
      restoration for advanced hypopharyngeal carcinoma after major surgery with
      ileocolic flap reconstruction. OBJECTIVES: To compare the results of adjuvant
      conventional radiotherapy (2DRT) with intensity modulated radiation therapy
      (IMRT) for locally advanced hypopharyngeal cancer after resection and ileocolic
      free flap reconstruction and to design treatment plans for those two modalities
      plus 3D conformal radiotherapy (3DCRT) for dose distribution comparison. METHODS:
      13 locally advanced hypopharyngeal cancer patients were enrolled, 8 treated with
      2DRT and 5 with IMRT. Different plans were planned for 3 IMRT-treated patients
      for comparing dose distribution. RESULTS: After major surgery, patients treated
      with IMRT had less toxicity and better functional restoration than those with
      2DRT. IMRT and 3DCRT both showed lower dose to the spinal cord than did 2DRT.
      Only IMRT showed reduced dose to ileocolic flap.

PMID- 18607976
TI  - Effects of hypergravity on histamine H1 receptor mRNA expression in hypothalamus
      and brainstem of rats: implications for development of motion sickness.
AB  - CONCLUSION: The study findings suggest that histamine was released from the axon
      terminals in the hypothalamus and brainstem and the released histamine activated
      post-synaptic H1 receptors there, resulting in the development of motion
      sickness. OBJECTIVES: We first examined which subtype of post-synaptic
      histaminergic receptor was responsible for the development of motion sickness. We
      then examined whether H1 receptors were up-regulated in various areas of the rat
      brain after 2 G hypergravity load, because the stimulation of H1 receptor was
      reported to up-regulate the level of H1 receptor protein expression through
      augmentation of H1 receptor mRNA expression. MATERIALS AND METHODS: For this
      purpose, we used an animal model of motion sickness, using pica (eating non
      nutritive substances such as kaolin), as a behavioral index in rats. RESULTS:
      After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating
      that they suffered from motion sickness. The hypergravity-induced kaolin intake
      was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding
      indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors
      play an important role in the development of motion sickness. The expression of
      H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in
      the cerebral cortex after 2 G hypergravity load in rats.

PMID- 18607978
TI  - Folded intraluminal drain tube stent in esophageal reconstruction with free
      jejunal flaps.
AB  - CONCLUSIONS: We believe that this method of nasogastric (NG) tube stenting has
      the potential to improve the overall result of esophageal reconstruction using
      free jejunal autografts. OBJECTIVES: Microvascular transfer of bowel segments for
      esophageal reconstruction is indicated in the treatment of esophageal defects. Of
      the late complications resulting from esophageal reconstruction with jejunal
      flaps, the most common are stricture and fistula. NG tubes are placed at the time
      of bowel transfer and inset for gastric decompression and intraluminal stenting.
      We developed and evaluated a method to decrease these associated risks from NG
      tube stenting, while at the same time maximizing its use as a neo-esophageal
      stent in an attempt to prevent stricture formation. PATIENTS AND METHODS: Forty
      two patients were evaluated from 1999 to 2004 who underwent cervical esophageal
      reconstruction following esophagectomy with a free jejunal autograft. An NG tube
      was folded proximally and secured to itself so that the doubled portion of the
      tube encompassed the reconstructed segment to decrease nasal airway morbidity and
      increase luminal dilatation and stenting. Timing of tube removal and
      complications were recorded. RESULTS: The length of follow-up was 24 months. The
      NG tube was removed in all cases at 2 weeks postoperatively following a normal
      esophagogram. There were no cases of esophageal perforation or dislodgement. Two
      patients (4.7%) developed an esophagocutaneous fistula and two patients (4.7%)
      developed a stricture requiring surgical correction. There were no incidences of
      sinusitis, alar necrosis, bleeding or mucosal ulceration.

PMID- 18607977
TI  - Are systemic prophylactic antibiotics indicated with anterior nasal packing for
      spontaneous epistaxis?
AB  - CONCLUSION: This pilot study did not show an advantage of the routine use of
      prophylactic antibiotics for spontaneous epistaxis treated by nasal packing.
      OBJECTIVE: The purpose of this study was to investigate the value of the use of
      prophylactic antibiotics in spontaneous epistaxis cases treated with anterior
      nasal packing. SUBJECTS AND METHODS: Over a period of 6 months, all cases of
      epistaxis managed with anterior nasal packing were studied prospectively. After
      pack removal, swabs from the packed and the non-packed sides of the nasal cavity
      were cultured to detect any difference in the bacterial growth pattern between
      the two sides. All these cases were clinically evaluated to detect any infection
      secondary to the anterior nasal packing. RESULTS: We did not observe infection in
      any of the cases before or after removal of the anterior nasal pack. The
      bacterial growth profile of packed and non-packed sides of the nose did not
      differ significantly.

PMID- 18607979
TI  - Non-epithelial lesions of the larynx: review of the 10-year experience in a
      tertiary Spanish hospital.
AB  - CONCLUSION: In this report we review the diagnosis, therapy, and outcome of
      laryngeal non-epithelial tumors and comment on the literature on these rare
      lesions. OBJECTIVES: Non-epithelial tumors of the larynx are rather rare and most
      cases have been reported as isolated or short series of cases from different
      centers all over the world. The aim of the present study was to review the 10
      year experience with non-epithelial lesions in a 400-bed tertiary hospital
      covering a population of almost 250 000 people in Madrid, Spain. PATIENTS AND
      METHODS: We reviewed 2631 laryngeal samples corresponding to this time period.
      RESULTS: In all, 737 corresponded to carcinomas (726 squamous cell carcinomas).
      We had two cases of chondrosarcoma, one case of liposarcoma, one case of synovial
      sarcoma, and one neural benign tumor, suggestive of neurinoma. In this period we
      also had an inflammatory pseudotumor affecting the vocal cord, a case of primary
      laryngeal extramedullary plasmocytoma, and one case of high grade diffuse
      malignant lymphoma with exclusive involvement of the larynx. In our series most
      patients were women (five vs three patients) and ages ranged between 12 and 92
      years.

PMID- 18607981
TI  - Therapeutic selective neck dissection (level II-V) for node-positive
      hypopharyngeal carcinoma: is it oncologically safe?
AB  - CONCLUSIONS: Our study suggests that routine level I dissection may not be
      necessary in the surgical management of clinically N + hypopharyngeal squamous
      cell carcinoma (SCC) in patients who do not have a positive lymph node in neck
      level I. OBJECTIVE: To determine whether level I lymph node dissection can be
      saved in patients with clinically N + hypopharyngeal SCC. PATIENTS AND METHODS:
      Retrospective analysis of 64 consecutive clinically N + patients with untreated
      hypopharyngeal SCC between 1994 and 2006. Forty-seven patients underwent level I
      lymph node dissection and the remaining 17 did not. Forty-five of the 64 patients
      were followed for a minimum of 2 years, if alive, or until death. Of these 45
      patients, 35 underwent ipsilateral level I dissection of the neck. RESULTS: The
      incidence of occult metastases to level I was 6% (3 of 47). Six (17%) of 35
      patients with level I dissection and 1 (10%) of 10 patients without level I
      dissection experienced regional recurrence (p>0.05). The 2-year disease-specific
      survival in 47 patients undergoing level I neck dissection was 44% compared with
      37% in 17 patients who did not undergo level I neck dissection (p>0.05).

PMID- 18607980
TI  - Subclinical deviation of the subjective visual vertical in patients affected by a
      primary headache.
AB  - CONCLUSION: Our results suggest that patients with migraine or tension-type
      headache have subclinical deviations of the subjective visual vertical, which may
      be associated with their subjective imbalance. OBJECTIVES: Patients affected by
      migraine or tension-type headache often complain of unsteadiness. However, they
      rarely show a clinical significance in the objective examinations of their
      equilibrium. We investigated the equilibrium functions in patients affected by
      migraine or tension-type headache. SUBJECTS AND METHODS: We investigated the
      neurotological findings of 17 patients with migraine, 20 patients with tension
      type headaches, and 16 patients without headache. All patients in this study
      experienced vertigo or dizziness before they underwent the examination; however,
      they never had vertigo attacks for more than 1 month before the examination. All
      patients in this study were tested during headache-free intervals. RESULTS: There
      was no significant difference in the hearing levels of pure tone audiometry, the
      canal palsy percentage of bithermal caloric test, and the body sway in
      posturography among the three groups (p>0.05, Mann-Whitney U test). The average
      values in absolute deviations of subjective visual vertical (SVV) in patients
      with tension-type headache (1.3+/-1.1 degrees ) and patients with migraine (1.5+/
      1.2 degrees ) were significantly larger in comparison with those of patients
      without headache (0.6+/-0.4) (p<0.05, Mann-Whitney U test). Intra-individual
      varaiances of the SVV in patients with primary headache were significantly larger
      than those in patients without headache (p<0.05, Mann-Whitney U test).

PMID- 18607982
TI  - A new integrated system for neural stimulation and bipolar coagulation:
      preliminary study.
AB  - CONCLUSION: The proposed device can be useful for promoting safety during bipolar
      coagulation in many surgical procedures and/or regions. OBJECTIVE: A new system
      that integrates a neural stimulator and a bipolar coagulator is proposed, to
      improve neural (facial nerve) safety during ENT surgical procedures. This study
      aimed to evaluate the system. MATERIALS AND METHODS: A home-made constant current
      neural stimulator (0.1-2 mA, pulsed, duration 200 micros), was connected via an
      automatic switch to a commercial bipolar microcoagulator (Medicon Instrumente
      mod. 101, Germany). Under general anesthesia, the extra-petrous portion of the
      facial nerve was identified in three rabbits. The adequate functioning of the
      device was tested via: 1) neural stimulation and EMG monitoring in basal
      conditions; 2) bipolar coagulation of connective tissue surrounding the facial
      nerve; 3) final assessment of the functional integrity of the nerve, via an
      intraoperative EMG and a postoperative evaluation. RESULTS: Data obtained from
      all three rabbits provided adequate results in terms of neural stimulation,
      correct coagulation of juxta-nervous tissue, and functional integrity of the
      facial nerve, both intraoperatively and postoperatively.

PMID- 18607983
TI  - Effects of gadolinium injected into the middle ear on the stria vascularis.
AB  - CONCLUSION: The concentration of gadolinium (Gd) used clinically showed no
      remarkable effects on the stria vascularis; however, a higher concentration had
      adverse effects. The concentration of Gd must be borne in mind when injecting Gd
      into the tympanic cavity. OBJECTIVE: Endolymphatic hydrops has been visualized
      using high resolution MRI with the intratympanic administration of Gd in patients
      with Meniere's disease. We attempted to investigate the effects of Gd on the
      stria vascularis. MATERIALS AND METHODS: Gd hydrate diluted eightfold with saline
      or non-diluted Gd or saline was injected into the tympanic cavity of guinea pigs.
      To investigate the effects of Gd on the stria vascularis, we measured
      endocochlear DC potential (EP) and observed the stria vascularis using
      transmission electron microscopy. RESULTS: Intratympanic injections of Gd hydrate
      diluted eightfold with saline (1/8 Gd) and saline did not cause apparent changes
      in the EP. Moreover, the amplitude of the EP decreased significantly 60 min after
      non-diluted Gd was injected. Transmission electron micrographs of the stria
      vascularis revealed no significant morphological difference between the ears
      injected with 1/8 Gd and those injected with saline. There was significant
      morphological change in the ear injected with non-diluted Gd. The intercellular
      spaces were markedly enlarged.

PMID- 18607984
TI  - Lingual distribution of the human glossopharyngeal nerve.
AB  - CONCLUSION: Nineteenth century anatomical descriptions of the anterior
      distribution of cranial nerve (CN) IX on the dorsal tongue are contrary to
      current concepts. By employing Sihler's stain, we demonstrated that, in fact, CN
      IX projects more anteriorly than the posterior third of the tongue. This may
      explain why some patients whose chorda tympani branch of CN VII has been severed
      during middle ear surgery continue to have taste function in sectors of the
      anterior two-thirds of the tongue. OBJECTIVE: To assess the anatomical
      distribution of CN IX on the lingual dorsum. MATERIALS AND METHODS: Three human
      cadaver tongues were microdissected following staining with Sihler's stain, a
      procedure that renders most of the tongue tissue translucent while
      counterstaining nerves. CN IX nerve branches were visually tracked within the
      tongue's dorsum. RESULTS: Branches of CN IX were observed that extended
      anteriorly beyond the sulcus terminalis and the circumvallate papillae, with
      extensions occurring along the lateral lingual margin anterior to the foliate
      papillae. Anastomoses were identified between CN IX and the lingual nerve,
      raising the possibility of functional interactions between CN V and CN IX.

PMID- 18607985
TI  - Diagnostic value of auditory brainstem responses in cerebellopontine angle
      tumours.
AB  - CONCLUSION: Auditory brainstem responses (ABRs) associated with other audio
      vestibular examinations and a thorough clinical examination should allow
      detection of the majority of cerebellopontine angle (CPA) lesions (99.2-100%).
      OBJECTIVE: The increasing quality of MRI in the detection of CPA lesions, and the
      reports of false negative ABRs have raised issues concerning the value of ABR in
      the diagnosis and preoperative assessment of CPA lesions. The aim of this work
      was to assess the value of the ABR in the diagnosis of vestibular schwannomas
      (VS) and other CPA lesions. PATIENTS AND METHODS: This retrospective study
      included 676 solitary VS (548 operated on and 128 followed up) and 70 other CPA
      tumours (72% meningiomas, 11% cholesteatomas, 3% ependymomas, 15% miscellaneous)
      managed between 1990 and 2001. All patients underwent clinical examination,
      audiometry, ABR, vestibular caloric tests and MRI. RESULTS: ABRs were normal in
      4.8% of VS. Association of normal ABR, vestibular caloric tests and audiometry
      (AAO-HNS class A) represented only 0.7% of VS. In other CPA lesions, ABR were
      normal in 15% of cases and the association of the three above-mentioned
      examinations was encountered in 10%. However, in the latter cases the clinical
      examination showed an abnormality in all cases.

PMID- 18607986
TI  - Endoscopic surgery for inverted papilloma originating from the sphenoid sinus and
      related clinical characteristics.
AB  - CONCLUSIONS: Bony changes on CT imaging of inverted papilloma (IP) are useful for
      predicting tumor origin and recurrence sites. Because the lateral wall and floor
      of the sphenoid sinus are the most common origin and recurrence sites, the
      anterior wall of the sphenoid sinus should be opened as wide as the lateral wall
      and inferiorly to the level of the floor, especially in deeply pneumatized
      sphenoid sinuses. OBJECTIVES: The incidence of isolated sphenoid IP is
      exceedingly low. So far, there have not been studies on the usual origin and
      recurrence sites of the sphenoid sinus. We sought to identify the sites of origin
      and recurrence and describe clinical characteristics, radiological features, and
      proper endoscopic management. PATIENTS AND METHODS: We retrospectively reviewed
      medical records of patients with IP of the sphenoid sinus. Data collection
      included clinical presentations, origin and recurrent sites, radiological
      features, and surgical methods. RESULTS: Seven patients were identified. The most
      common symptoms were headache and nasal obstruction. Radiological findings showed
      that most tumors extended into the nasal cavity or ethmoid sinus combined
      frequently with erosion of the lateral wall or intersinus septum. We noted
      simultaneous attachment to multiple walls in five subjects, including both
      lateral wall and floor attachment in three subjects.

PMID- 18607988
TI  - Mutation analysis of the Cx26, Cx30, and Cx31 genes in autosomal recessive
      nonsyndromic hearing impairment.
AB  - CONCLUSION: Biallelic Cx26 mutations are the most common cause of autosomal
      recessive nonsyndromic hearing impairment (ARNHI) in Switzerland. Mutations in
      Cx30 and 31, digenic mutations as well as large deletions/duplications, are
      unlikely to be a major cause of hearing loss in Swiss patients with ARNHI.
      Multiplex ligation-dependent probe amplification (MLPA) is a highly accurate
      screening method for detection of c.del(GJB6-D13S1830). OBJECTIVES: The intent of
      this study was to investigate the prevalence of the point and digenic mutations
      including large deletions and duplications in the Cx26, 30, and 31 genes in a
      Swiss patient cohort with ARNHI and cochlear implant. PATIENTS AND METHODS: The
      coding regions of Cx26, 30, and 31 were sequenced in 32 patients. Large
      deletions/duplications were assessed by MLPA. RESULTS: In one patient digenic
      heterozygous mutations involving Cx26 (c.35delG) and Cx30 (c.del(GJB6-D13S1830))
      were identified. Biallelic Cx26 mutations were detected in 31%. One putative
      mutation (c.94C>T) was found in Cx31. MLPA analysis did not reveal any additional
      deletion or duplication in all three Cx genes, except for the heterozygous
      c.del(GJB6-D13S1830) deletion.

PMID- 18607989
TI  - Relationship between adenoid vegetation and anatomic variations of paranasal
      sinuses.
AB  - CONCLUSION: We could not demonstrate an effect of adenoid vegetation on
      development of paranasal sinus anatomic variations. OBJECTIVE: To investigate
      whether adenoid vegetation has an impact on anatomic variations of paranasal
      sinuses. PATIENTS AND METHODS: Fifty-six children with adenoid vegetation and 25
      children without adenoid vegetation were enrolled in the study. The paranasal
      sinus anatomic variations were investigated via coronal section CT scans.
      RESULTS: No statistically significant difference was noticed between children
      with and without adenoid vegetation. In addition, no significant correlation with
      respect to age of children and anatomic variations was determined.

PMID- 18607990
TI  - Chronic subjective dizziness.
AB  - CONCLUSION: Chronic subjective dizziness (CSD) is frequent and affects twice as
      many women as men. Anxiety is a strong predisposing factor. The pathophysiologic
      concept of this disorder assumes that balance function and emotion share common
      neurologic pathways, which might explain that the balance disorder can provoke
      fear and vice versa, giving rise to a problem in perception of space and motion.
      In anxious patients this can turn into a space and motion phobia, with avoidance
      behaviour. OBJECTIVE: CSD is a diagnosis based on the hypothesis of an
      interaction between the vestibular system and the psychiatric sphere. Patients
      complain of chronic imbalance, worsened by visual motion stimulation, and
      frequently suffer from anxiety. Vestibular examination reveals no anomalies. We
      evaluated the incidence and characteristics of CSD in patients referred to our
      neuro-otology centre (tertiary hospital outpatient clinic). SUBJECTS AND METHODS:
      This was a retrospective study of 1552 consecutive patients presenting with
      vertigo. CSD was diagnosed in 164 patients (female:male=111:53). RESULTS: CSD
      represents 10.6% of the dizzy patients in our clinic. Psychiatric disorder,
      mainly anxiety, was found in 79.3% of the cases. Other frequently associated
      factors were fear of heights and former vestibular lesion (healed). In all, 79.0%
      of the patients with CSD had poor balance performance on dynamic posturography
      testing.

PMID- 18607991
TI  - Proapoptotic effects of NF-kappaB on cisplatin-induced cell death in auditory
      cell line.
AB  - CONCLUSIONS: The findings suggest that nuclear factor (NF)-kappaB is activated by
      cisplatin and plays a proapoptotic role during cell death in the auditory cell
      line HEI-OC1. OBJECTIVES: Cisplatin is a very effective antineoplastic drug but
      in high doses it shows ototoxicity by inducing apoptosis of hair cells in the
      cochlea. NF-kappaB is a transcription factor regulating apoptosis in many organs
      and tissues. This study examined the role of NF-kappaB in the apoptotic pathway
      induced by cisplatin in the auditory cell line, HEI-OC1. MATERIALS AND METHODS:
      Apoptotic cell death was identified by measuring caspase 3 activity and
      immunostaining with anti-caspase 3 antibody after cisplatin treatment (50 microM)
      for 24 h. To investigate the role of NF-kappaB in apoptotic cell death, HEI-OC1
      cells treated with 50 microM of cisplatin were immunostained with anti-NF-kappaB
      (p65) antibody. Two different NF-kappaB inhibitors, Bay 11-7085 and SN-50, were
      co-incubated with cisplatin (50 microM) for 24 h and caspase 3 activity was
      assayed. RESULTS: Immunostaining with anti-caspase 3 antibody and caspase 3 assay
      showed that cisplatin induced apoptosis in HEI-OC1 cells. After cisplatin
      treatment, NF-kappaB (p65) was activated to translocate from the cytoplasm into
      the nucleus. Co-treatment with NF-kappaB inhibitors reduced the cisplatin-induced
      apoptosis of HEI-OC1 cells.

PMID- 18607994
TI  - High concentrations of thiosulfate in scala tympani perilymph after systemic
      administration in the guinea pig.
AB  - CONCLUSION: High concentrations of the antioxidant thiosulfate reach scala
      tympani perilymph after i.v. administration in the guinea pig. Thiosulfate
      concentrations in perilymph remain elevated longer than in blood. This warrants
      further studies on the possibility of obtaining otoprotection by thiosulfate
      administration several hours before that of cisplatin without compromising the
      anticancer effect caused by cisplatin inactivation in the blood compartment.
      OBJECTIVE: Thiosulfate may reduce cisplatin-induced ototoxicity, presumably by
      oxidative stress relief and formation of inactivate platinum complexes. This
      study aimed to explore to what extent thiosulfate reaches scala tympani perilymph
      after systemic administration in the guinea pig. MATERIALS AND METHODS: Scala
      tympani perilymph (1 microl) was aspirated from the basal turn of each cochlea up
      to 3 h after thiosulfate administration (103 mg/kg b.w., i.v.). Blood samples
      were also taken. Thiosulfate was quantified by HPLC and fluorescence detection.
      RESULTS: Substantial thiosulfate concentrations were found in perilymph. The area
      under the concentration-time curve for thiosulfate in perilymph and blood was
      3100 microMxmin and 6300 microMxmin, respectively. The highest thiosulfate
      concentrations in perilymph were found at the first sampling at about 10 min. Due
      to a more rapid elimination from blood, perilymph concentrations exceeded those
      of blood towards the end of the experiment.

PMID- 18607996
TI  - Effect of human papilloma virus expression on clinical course of laryngeal
      papilloma.
AB  - CONCLUSION: Our observations suggest that human papilloma virus (HPV) 6/11 is the
      main causative agent of laryngeal papilloma and that detection of active HPV DNA
      expression may be helpful in identifying patients with aggressive recurrent
      laryngeal papilloma. OBJECTIVES: HPV is assumed to be the main causative agent of
      this disease. We investigated the expression of the entire genotype of HPV in
      cases of laryngeal papilloma and correlated their expression with the clinical
      course of the disease. SUBJECTS AND METHODS: Seventy cases of laryngeal papilloma
      were evaluated for the presence of the HPV genome by in situ hybridization (ISH)
      using wide-spectrum HPV DNA probe. Specific types of HPV infection were
      determined by DNA ISH using type-specific HPV DNA probes (HPV 6, 11, 16, 18, 31,
      33). Separate analyses were conducted comparing viral types, frequency of
      recurrences and duration of disease-free periods. RESULTS: We detected HPV DNA in
      40 of the 70 laryngeal papilloma cases (57%). In particular, HPV DNA was detected
      in 75% of the juvenile types. There were significant associations between HPV and
      laryngeal papilloma (p<0.01). Among the HPV-positive cases, major specific types
      were HPV 6/11 (97%). Significant associations were also noted between viral
      expression and clinical course.

PMID- 18607998
TI  - Additive effects of oral fluoropyrimidine derivative S-1 and radiation on human
      hypopharyngeal cancer xenografts.
AB  - CONCLUSION: The results presented here provide evidence of the enhancing effect
      of oral fluoropyrimidine derivative S-1 in concomitant chemoradiotherapy for head
      and neck cancer and further insights into its biological mechanism. OBJECTIVE: To
      investigate the additive effect of S-1 and radiation for human hypopharyngeal
      cancer. MATERIALS AND METHODS: Nude mice bearing hypopharyngeal cancer cells
      (H891) were used for an in vivo model. S-1 was administered at a volume of 0.01
      mg/g body weight per mouse for 14 days, and tumors were irradiated with 2.0 Gy on
      days 1 and 8. Mice treated with either radiation or S-1 alone were used as
      controls. The growth of tumors in each group was measured and, after completion
      of the treatment, a focused DNA array was used to determine mRNA expression
      levels in the tumors of 132 genes related to 5-fluorouracil (5-FU), radiation or
      carcinogenesis. RESULTS: The additive antitumor effect of S-1 and radiation was
      statistically confirmed on day 14 (p=0.01). DNA array assay showed significant
      changes in expression of several genes, including DNA repair gene POLD,
      angiogenesis-related genes bFGF and TP, DNA topoisomerase TOP2A, and nucleoside
      transporter gene ENT1.

PMID- 18608002
TI  - Presence of hBD-1 and hBD-2 in human cerumen and external auditory canal skin.
AB  - CONCLUSION: Human beta-defensin-1 (hBD-1) and human beta-defensin-2 (hBD-2)
      antimicrobial peptides present in the cerumen, which is composed of exfoliated
      epithelial keratin and gland secretion, might provide the first line of defense
      against microbes in external auditory canal (EAC) skin. OBJECTIVES: Cerumen
      (earwax) plays a primary role in protecting the EAC skin and tympanic membrane.
      Even though the protection by antimicrobial peptides present in the skin
      secretion has been well established, little is known about the intrinsic role of
      the peptides in the EAC skin and cerumen. The aim of this study was to examine
      the presence of important antimicrobial peptides, hBD-1 and hBD-2, in the cerumen
      and EAC skin. MATERIALS AND METHODS: Cerumen was collected from 20 healthy
      adults, and the EAC skins were obtained from 12 patients who underwent middle ear
      surgery with canaloplasty. The presence of hBD-1 and hBD-2 was analyzed using
      immunohistochemistry and Western blotting. RESULTS: In the immunohistochemical
      study of the EAC skin, expression of hBD-1 and hBD-2 was observed in both the
      epithelium and the glands. The presence of hBD-1 and hBD-2 peptides in the
      cerumen was confirmed by Western blotting.

PMID- 18608005
TI  - Effects of Japanese herbal medicine, Juzen-taiho-to, in otitis-prone children--a
      preliminary study.
AB  - CONCLUSION: Juzen-taiho-to (JTT, TJ-48), a Japanese herbal medicine that improves
      immune function, was found to be effective in otitis-prone in children.
      OBJECTIVE: To evaluate the efficacy of JTT against intractable and recurrent
      infections in immature immune systems, we administered JTT to otitis-prone
      infants and investigated clinical changes before and during JTT administration.
      SUBJECTS AND METHODS: Twenty-four otitis-prone infants were administered JTT at
      0.10-0.14 g/kg/day twice a day for 3 months. We compared clinical course, such as
      frequency of acute otitis media (AOM), duration of fever and antibiotics
      administration, and hospital visits for the periods before and during JTT
      administration. RESULTS: Medication compliance rate was 87.5%, and administration
      of JTT led to remission in 95.2% patients. No apparent side effects were
      observed. The frequency of AOM decreased significantly (Wilcoxon signed rank
      test, p=0.000) with JTT. The duration of fever (p=0.000) and administration of
      antibiotics (p=0.001), as well as the number of hospital visits (p=0.001) and
      emergent hospital visits (p=0.000) showed significant decreases after JTT
      administration. After the end of the JTT period, 14 of 21 (66.7%) patients
      started to take it again, as they experienced purulent otitis media and/or other
      infections after discontinuation. The frequency of AOM increased significantly
      after stopping JTT (p=0.004) and decreased again with JTT resumption (p=0.005).

PMID- 18608007
TI  - Adjusting results for confounding bias.

PMID- 18608006
TI  - Actin filaments and microtubules regulate endocytosis in marginal cells of the
      stria vascularis.
AB  - CONCLUSION: Cationized ferritin (CF) was internalized via clathrin-mediated
      endocytosis. This process depends on clathrin, actin filaments, and microtubules.
      Microperoxidase (MPO) was internalized via a clathrin- and caveolin-independent
      endocytic pathway, which was partially dependent on microtubules but independent
      of clathrin and actin filaments. OBJECTIVE: We investigated the role of actin
      filaments and microtubules in the transport of endocytic carrier vesicles (ECVs)
      from the plasma membrane to the early sorting endosomes, using CF and MPO as
      tracers. MATERIALS AND METHODS: Fifty-five guinea pigs were used. The animals
      were divided into a CF endocytosis group and an MPO endocytosis group. These
      groups consisted of control, nocodazole-treated, cytochalasin (Cyt D)-treated,
      Cyt D + nocodazole-treated, and geldanamycin-treated subgroups. RESULTS: For CF
      endocytosis, the following results were obtained. In the nocodazole experiment,
      in which microtubules were disrupted to form monomeric tubulin, the number of
      ECVs loaded with CF was greatly decreased. In the Cyt D experiment, in which the
      actin filaments were disrupted to form monomers, the number of ECVs labeled with
      CF was also greatly decreased. In the geldanamycin experiment, in which clathrin
      mediated endocytosis was regulated and actin stress fibers were dissolved, the
      endocytosis of CF was severely inhibited. For MPO endocytosis, in the nocodazole
      experiment, the endocytosis of MPO was markedly suppressed.

PMID- 18608008
TI  - Planning a randomized trial.

PMID- 18608009
TI  - The use of virtual reality for training in carotid artery stenting: a construct
      validation study.
AB  - BACKGROUND: Given that carotid artery stenosis (CAS) intervention is procedurally
      difficult, possesses an extensive learning curve, and involves a grave list of
      potential complications, construct validation of new non-clinical training
      devices is of increasing importance. PURPOSE: To evaluate the construct validity
      of the Procedicus-Virtual Interventional Simulator Trainer (Procedicus-VIST) and
      its use as a training tool. MATERIAL AND METHODS: Sixteen interventionalists (15
      males, one female; mean interventional radiology [IR] experience >11 years) and
      16 medical students (15 males, one female; no IR experience) received 1 hour of
      didactic instruction followed by an hour of familiarization training. Subjects
      then attempted to complete a carotid artery stenting procedure within 1 hour
      while their performance metrics were recorded. All participants completed a
      qualitative exit survey of subjective parameters using a visual analog scale.
      RESULTS: Procedure and fluoroscopic time was 8.7 and 8.7 min greater in the
      novice group (P=0.0066 and P=0.0031), respectively. There were no significant
      differences in performances between the two groups in the remaining metrics of
      cine loops (number recorded), tool/vessel ratio, coverage percentage, and
      placement accuracy or residual stenosis. Contrast measurement metrics were found
      to be too imprecise for statistical analysis. Experienced and novice opinions
      differed significantly for six of 10 subjective parameters. No statistically
      significant difference in video-gaming habits was demonstrated. CONCLUSION: With
      the exception of the metrics of performance time and fluoroscopic use, construct
      validity of the Procedicus-VIST carotid metrics were not confirmed. Virtual
      reality simulation as a training method was valued more by novices than by
      experienced interventionalists.

PMID- 18608011
TI  - Data handling, statistical computing, and archiving.

PMID- 18608012
TI  - Detection of cholangiocarcinoma with magnetic resonance spectroscopy of bile in
      patients with and without primary sclerosing cholangitis.
AB  - BACKGROUND: Early detection of cholangiocarcinoma (CC) is very difficult,
      especially in patients with primary sclerosing cholangitis (PSC) who are at
      increased risk of developing CC. PURPOSE: To evaluate 1H magnetic resonance
      spectroscopy ((1)H-MRS) of bile as a diagnostic marker for CC in patients with
      and without PSC. MATERIAL AND METHODS: The institutional review board approved
      the study, and all patients gave informed consent. Bile from 49 patients was
      sampled and investigated using 1H-MRS. MR spectra of bile samples from 45
      patients (18 female; age range 22-87 years, mean age 57 years) were analyzed both
      conventionally and using computerized multivariate analysis. Sixteen of the
      patients had CC, 18 had PSC, and 11 had other benign findings. RESULTS: The
      spectra of bile from CC patients differed from the benign group in the levels of
      phosphatidylcholine, bile acids, lipid, and cholesterol. It was possible to
      distinguish CC from benign conditions in all patients with malignancy. Two benign
      non-PSC patients were misclassified as malignant. The sensitivity, specificity,
      and accuracy were 88.9%, 87.1%, and 87.8%, respectively. CONCLUSION: With 1H-MRS
      of bile, cholangiocarcinoma could be discriminated from benign biliary conditions
      with or without PSC.

PMID- 18608014
TI  - Improvement of detection of hypoattenuation in acute ischemic stroke in
      unenhanced computed tomography using an adaptive smoothing filter.
AB  - BACKGROUND: Much attention has been directed toward identifying early signs of
      cerebral ischemia on computed tomography (CT) images. Hypoattenuation of ischemic
      brain parenchyma has been found to be the most frequent early sign. PURPOSE: To
      evaluate the effect of a previously proposed adaptive smoothing filter for
      improving detection of parenchymal hypoattenuation of acute ischemic stroke on
      unenhanced CT images. MATERIAL AND METHODS: Twenty-six patients with parenchymal
      hypoattenuation and 49 control subjects without hypoattenuation were
      retrospectively selected in this study. The adaptive partial median filter (APMF)
      designed for improving detectability of hypoattenuation areas on unenhanced CT
      images was applied. Seven radiologists, including four certified radiologists and
      three radiology residents, indicated their confidence level regarding the
      presence (or absence) of hypoattenuation on CT images, first without and then
      with the APMF processed images. Their performances without and with the APMF
      processed images were evaluated by receiver operating characteristic (ROC)
      analysis. RESULTS: The mean areas under the ROC curves (AUC) for all observers
      increased from 0.875 to 0.929 (P = 0.002) when the radiologists observed with the
      APMF processed images. The mean sensitivity in the detection of hypoattenuation
      significantly improved, from 69% (126 of 182 observations) to 89% (151 of 182
      observations), when employing the APMF (P = 0.012). The specificity, however, was
      unaffected by the APMF (P = 0.41). CONCLUSION: The APMF has the potential to
      improve the detection of parenchymal hypoattenuation of acute ischemic stroke on
      unenhanced CT images.

PMID- 18608013
TI  - Prevalence of coronary artery intramyocardial course in a large population of
      clinical patients detected by multislice computed tomography coronary
      angiography.
AB  - BACKGROUND: Intramyocardial course, an inborn coronary anomaly, is defined as a
      segment of a major epicardial coronary artery that runs intramurally through the
      myocardium; in particular, we distinguish myocardial bridging, in which the
      vessel returns to an epicardial position after the muscle bridge, and
      intramyocardial course, which is described as a vessel running and ending in the
      myocardium. PURPOSE: To evaluate the prevalence of myocardial bridging and
      intramyocardial course of coronary arteries as defined by multidetector computed
      tomography (MDCT) angiography. MATERIAL AND METHODS: The study population
      consisted of 242 consecutive patients (211 men, 31 women; mean age 59+/-6 years)
      with atypical chest pain admitted to our hospital between December 2004 and
      September 2006. All MDCT examinations were performed using a 16-detector-row
      scanner (Aquilion 16 CFX; Toshiba Medical System, Tokyo, Japan). Patients with
      heart rate above 65 bpm received 50 mg atenolol orally for 3 days prior to the
      MDCT scan, or they increased their usual therapy with beta-blockers, in order to
      obtain a prescan heart rate <60 bpm. Curved multiplanar and 3D volume
      reconstructions were performed to explore coronary anatomy. RESULTS: In 235
      patients, the CT scan was successful and images were appropriate for evaluation.
      The prevalence of myocardial bridging and intramyocardial course of coronary
      arteries was 18.7% (47 cases) in our patient population. In 30 segments (63.8%),
      the vessels ran and ended in the myocardium. In the remaining 17 segments
      (36.2%), the vessels returned to an epicardial position after the muscle bridge.
      We found no difference in the prevalence of this inborn coronary anomaly when
      comparing different clinical characteristics of the study population (sex, age,
      body-mass index [BMI], etc.). The mean length of the subepicardial artery was 7
      mm (range 5-12 mm), and the mean depth in the diastolic phase was 1.9 mm (range
      1.2-2.3 mm). There was no significant difference of diameter in these segments
      between the different R-R phases examined. CONCLUSION: Our study is in agreement
      with major angiographic literature reporting a prevalence of myocardial bridging
      and intramyocardial course between 0.5% and 33%. MDCT technology represents a
      useful, noninvasive imaging method to assess and evaluate the location, depth,
      and length of this anatomical variation.

PMID- 18608015
TI  - Small hypervascular hepatocellular carcinoma: limited value of portal and delayed
      phases on dynamic magnetic resonance imaging.
AB  - BACKGROUND: Characterization of small nodules in the cirrhotic liver is always
      challenging in clinical practice. In the differential diagnosis of small
      hypervascular lesions, it has been reported that portal venous or delayed
      hypointensity is a useful sign to characterize hepatocellular carcinomas (HCCs)
      during dynamic magnetic resonance (MR) imaging. However, few studies have
      assessed the diagnostic value of this sign. PURPOSE: To determine the diagnostic
      value of portal-phase (PP) and delayed-phase (DP) images for the diagnosis of
      small hypervascular HCCs during intravenous (IV) contrast-enhanced dynamic MR
      imaging of cirrhotic liver. MATERIAL AND METHODS: A total of 69 small (6-20 mm)
      hypervascular HCCs in 53 cirrhotic patients were subjected to a retrospective
      analysis of the signal intensities (hypo-, iso-, or hyperintense) and rim
      enhancement on PP and 5-min DP images from three-phased dynamic MR imaging
      according to the pre-contrast T1- and T2-weighted imaging features. After
      exclusion of 33 subcapsular wedge-shaped pseudolesions and three hemangiomas by
      typical imaging features, 74 centrally located small hypervascular benign or
      pseudolesions were used as a control group for comparative analyses. RESULTS: The
      sensitivities of PP hypointensity, DP hypointensity, and rim enhancement in the
      diagnosis were 11%, 29%, and 18%, respectively, for 6-10-mm hypervascular HCCs,
      and 42%, 63%, and 58%, respectively, for 16-20-mm lesions. After exclusion of the
      48 lesions showing T2-weighted hyperintensity (HCCs, n = 39; benign lesions, n =
      9), the overall sensitivity for diagnosis of small hypervascular HCCs decreased
      (8.3%, 25.0%, and 8.3%, respectively). CONCLUSION: Although DP provides a better
      sensitivity than PP, both PP and DP have very limited diagnostic value for
      diagnosis of small hypervascular HCCs during dynamic MR imaging of the cirrhotic
      liver.

PMID- 18608016
TI  - Fat-suppressed T2* sequences for routine 3.0-tesla lumbar spine magnetic
      resonance imaging: a preliminary report.
AB  - BACKGROUND: Clear depiction of the ligamentum flavum on routine lumbar magnetic
      resonance imaging (MRI) is essential in accurately describing the extent of
      degenerative disease. In routine, noncontrast evaluations, focal fatty deposition
      or hemangiomas can be difficult to distinguish from malignant foci on fast spin
      echo (FSE) T2-weighted images. PURPOSE: To describe the use of T2* fast field
      echo (T2FFE) in combination with spectral presaturation inversion recovery (SPIR)
      fat suppression for noncontrast, routine lumbar spine outpatient MR imaging at
      3.0 Tesla (3T). MATERIAL AND METHODS: An axial gradient echo (GE) T2FFE sequence
      was combined with SPIR fat suppression (T2FFE-SPIR), via a 3T Philips Intera
      (Philips Medical Systems, Best, The Netherlands) scanner, and added to the
      routine, noncontrast lumbar MRI examinations, which included sagittal FSE T1
      weighted (T1WI), T2-weighted (T2WI), short-tau inversion recovery (STIR), and
      axial FSE T2WI. The sequence was performed in over 500 patients over a 1-year
      period, without intravenous contrast, and with slice thickness and planes of
      section identical to the axial FSE T1WI and T2WI images. The sequence typically
      lasted about 4.5-6 min. RESULTS: The use of T2FFE-SPIR enabled visualization of
      the ligamentum flavum in degenerative disease, and the exclusion of focal fatty
      lesions on FSE T2WI. Other benefits included: the identification of malignant
      foci, the uncommon detection of hemorrhage, and the elimination of spurious flow
      voids. Several brief examples are provided to demonstrate the utility of this
      technique. CONCLUSION: The addition of T2FFE-SPIR to routine, noncontrast
      protocols in outpatients could provide further confidence in the visualization of
      the ligamentum flavum in degenerative disease, and can exclude malignancy in T2
      bright areas of focal fatty marrow. Larger studies would be helpful to evaluate
      the accuracy of this technique versus FSE techniques in depicting degenerative,
      malignant, or inflammatory disorders.

PMID- 18608018
TI  - The prognostic role of magnetic resonance imaging and single-photon emission
      computed tomography in viral encephalitis.
AB  - BACKGROUND: There is a paucity of studies evaluating the prognostic role of
      magnetic resonance imaging (MRI) and single-photon emission computed tomography
      (SPECT) changes in viral encephalitis. PURPOSE: To study MRI and SPECT changes in
      patients with viral encephalitis, and to correlate these changes with clinical
      findings and outcome. MATERIAL AND METHODS: During 1997-2006, 31 encephalitis
      patients (aged 2-60 years; nine females, 22 males) underwent both MRI and SPECT
      studies. Their demographic and clinical data and 6-month outcome were recorded.
      For the diagnosis of encephalitis, polymerase chain reaction (PCR) and IgM enzyme
      linked immunosorbent assay (ELISA) were carried out. Cranial MRI was done on a
      1.5T scanner, and 99mTc ethylene cysteine dimer (ECD) SPECT using a gamma camera.
      Outcome was defined at 6 months as complete, partial, or poor recovery. RESULTS:
      19 patients had Japanese encephalitis (JE), one had herpes simplex encephalitis
      (HSE), and 11 had nonspecific encephalitis. Movement disorders were present in
      21, parkinsonian features in 19, and dystonia in 16 patients. MRI was abnormal in
      20 patients, and revealed thalamic involvement in 17, basal ganglia in eight,
      brainstem in 11, and cortical in two. SPECT revealed hypoperfusion in 22
      patients, which was cortical in 11, thalamic in 10, basal ganglia in six, and
      midbrain in one. Cortical involvement was more frequently found by SPECT and
      brainstem involvement by MRI. Outcome of encephalitis did not differ in the
      different groups of encephalitis and MRI changes. CONCLUSION: MRI and SPECT show
      a spectrum of findings in encephalitis, but these do not correlate with 6-month
      outcome.

PMID- 18608020
TI  - Effects of different compression techniques on diagnostic accuracies of breast
      masses on digitized mammograms.
AB  - BACKGROUND: The JPEG 2000 compression technique has recently been introduced into
      the medical imaging field. It is critical to understand the effects of this
      technique on the detection of breast masses on digitized images by human
      observers. PURPOSE: To evaluate whether lossless and lossy techniques affect the
      diagnostic results of malignant and benign breast masses on digitized mammograms.
      MATERIAL AND METHODS: A total of 90 screen-film mammograms including craniocaudal
      and lateral views obtained from 45 patients were selected by two non-observing
      radiologists. Of these, 22 cases were benign lesions and 23 cases were malignant.
      The mammographic films were digitized by a laser film digitizer, and compressed
      to three levels (lossless and lossy 20:1 and 40:1) using the JPEG 2000 wavelet
      based image compression algorithm. Four radiologists with 10-12 years' experience
      in mammography interpreted the original and compressed images. The time interval
      was 3 weeks for each reading session. A five-point malignancy scale was used,
      with a score of 1 corresponding to definitely not a malignant mass, a score of 2
      referring to not a malignant mass, a score of 3 meaning possibly a malignant
      mass, a score of 4 being probably a malignant mass, and a score of 5 interpreted
      as definitely a malignant mass. The radiologists' performance was evaluated using
      receiver operating characteristic analysis. RESULTS: The average Az values for
      all radiologists decreased from 0.8933 for the original uncompressed images to
      0.8299 for the images compressed at 40:1. This difference was not statistically
      significant. The detection accuracy of the original images was better than that
      of the compressed images, and the Az values decreased with increasing compression
      ratio. CONCLUSION: Digitized mammograms compressed at 40:1 could be used to
      substitute original images in the diagnosis of breast cancer.

PMID- 18608021
TI  - Shoulder magnetic resonance arthrography: a prospective randomized study of
      anterior and posterior ultrasonography-guided contrast injections.
AB  - BACKGROUND: Magnetic resonance (MR) arthrography is an accurate imaging method
      for internal shoulder derangements and rotator cuff pathologies. Both anterior
      and posterior contrast injection techniques, under palpatory, fluoroscopic, or
      ultrasonographic guidance have been described in the literature. However,
      clinical comparisons of the injection techniques remain few. PURPOSE: To compare
      the performance of anterior and posterior ultrasonography (US)-guided
      arthrography injections of the shoulder regarding patient discomfort and
      influence on diagnostic MR reading, and to illustrate the typical artifacts
      resulting from contrast leakage in the respective techniques. MATERIAL AND
      METHODS: 43 MR arthrographies were prospectively randomized into anterior and
      posterior US-guided contrast injections and performed by two radiologists, with
      the study of artifacts from contrast leakage. Pain from the injections was
      assessed by a survey utilizing a 100-mm visual analogue scale (VAS). RESULTS: Of
      the 23 anterior injections, nine caused contrast artifacts in the subscapular
      tendon, and in three the leakage extended further anteriorly. Of the 20 posterior
      injections, 12 showed injection artifacts of the rotator cuff, extending outside
      the cuff in seven. Two of the anterior and none of the posterior artifacts
      compromised diagnostic quality. In posterior injections, the leakage regularly
      occurred at the caudal edge of the infraspinatus muscle and was easily
      distinguishable from rotator cuff tears. All patients completed the pain survey.
      Mean VAS scores were 25.0 (median 18, SD 22) for anterior, and 25.4 (median 16,
      SD 25) for posterior injections. The two radiologists achieved different mean VAS
      scores but closely agreed as to anterior and posterior VAS scores. CONCLUSION:
      Arthrography injections were fairly simple to perform under US guidance. Patient
      discomfort for anterior and posterior injections was equally minor. A tailored
      approach utilizing anterior or posterior injections, depending on anticipated
      shoulder pathology, is recommended. Because in posterior injections all artifacts
      were posterior and readily recognizable, it seems especially suitable for
      suspected anterior rotator cuff, joint capsule, and labral pathologies.

PMID- 18608026
TI  - Underdiagnosis of vertebral collapse on routine multidetector computed tomography
      scan of the abdomen.
AB  - BACKGROUND: Vertebral fractures are commonly associated with osteoporosis and
      have significant morbidity and mortality rates. Osteoporotic vertebral fractures
      are presently considered as a treatable and preventable condition, and early
      detection is vital for further management. The evaluation of vertebral
      compression on multidetector computed tomography (MDCT) scans of the abdomen has,
      to our knowledge, not been reported before. PURPOSE: To assess the prevalence of
      vertebral collapse on routine abdominal CT scans, and to evaluate the usefulness
      of the multiplanar reconstruction (MPR) capability of MDCT scans in accurately
      identifying vertebral abnormalities such as vertebral collapse,
      spondylolisthesis, and retrolisthesis. MATERIAL AND METHODS: A retrospective
      review of 307 MDCT scans of the abdomen was carried out at a university teaching
      hospital. Identifiable patient information was anonymized for data protection.
      All images were reviewed on a picture archiving and communications system (PACS)
      using sagittal MPR and bone window for the assessment of the vertebrae. Data were
      collected from the Computerized Radiology Information System (CRIS). RESULTS:
      Vertebral collapse was seen in 42 (13.6%) of the 307 patients undergoing routine
      MDCT of the abdomen. Multilevel and single-level collapses were seen in 24 and 18
      patients, respectively. Spondylolisthesis was identified in 5.5% (n = 17), and
      retrolisthesis was seen in 0.6% (n = 2). All patients with vertebral fracture
      were older than 50 years. Women were more commonly affected than men. CONCLUSION:
      A significant number of patients with vertebral collapse were diagnosed using MPR
      on MDCT routine scans of the abdomen.

PMID- 18608028
TI  - Analyzing a randomized trial.

PMID- 18608031
TI  - Bone marrow edema: pathophysiology, differential diagnosis, and imaging.
AB  - Bone marrow edema (BME) has been a topic of increasing interest in the literature
      in recent years. BME is associated with numerous pathologies and is becoming
      recognized not only as a considerable pain generator, but also as an entity which
      is, in some cases, significantly linked to the worsening of patient prognosis. To
      date, no thorough imaging review of BME has been published. An electronic
      literature search was conducted through PubMed with a time parameter of January
      1975 through December 2007. The primary search parameter was "bone marrow edema."
      Over 800 papers were listed as written in English and involving humans. Other
      refining parameters included "AND syndrome," "AND transient," "AND arthritis,"
      "AND infection," "AND tumor," "AND neoplasm," "AND iatrogenic," "AND radiation
      therapy," and "AND inflammation." More current articles were favored over dated
      articles on the same topic. A total of 106 journal articles were collected
      concerning BME and multiple pathologic processes. The data contained therein was
      compiled and organized into a comprehensive format. BME can be caused by, and
      found concurrent with, a broad spectrum of pathologies which exhibit a variety of
      imaging findings. BME is also associated with the deterioration of certain
      pathologies. This presentation is a comprehensive discussion of different
      pathological conditions inducing or associated with BME. Differential diagnosis
      through appropriate imaging is vital to case management and could contribute to
      the prevention or decreased progression of certain pathologies. Continued
      investigation into the imaging of BME and its associated diseases, as well as the
      effect of BME on prognosis, is warranted.

PMID- 18608032
TI  - Percutaneous coronary intervention on single saphenous vein 'snake' bypass graft
      supplying eight target vessels.

PMID- 18608033
TI  - Transfer for primary angioplasty in elderly patients with acute myocardial
      infarction.
AB  - INTRODUCTION: The aim of this study was the evaluation of an immediate transfer
      for primary angioplasty (PPCI) in elderly (age > or = 75 years) patients with ST
      elevation acute myocardial infarction (STEMI). METHODS AND MATERIALS: All elderly
      patients with STEMI admitted for PPCI from June 2002 to October 2005, were
      enrolled. Major Adverse Cardiac Events (MACE) were collected at 6 months.
      RESULTS: 133 patients (group 1) were admitted directly and 154 patients (group 2)
      were transferred from peripheral hospitals. Ischemia time was 248 +/- 146 min in
      group 1 and 276 +/- 169 min in group two (P<0.001); door-to-balloon time was 60+/
      30 min in group 1 and 90+/-45 min in group two (P<0.0001). At 6 months cardiac
      death occurred in 15 (11%) and 16 (10%) patients in group 1 and 2 respectively
      (P=NS), MI in 3(2%) and 2(1%) respectively (P=NS), clinically driven target
      lesion revascularization in 6(4%) and 5(3%) respectively, for an overall event
      free survival rate of 82% in group 1 and 83% in group 2 (P=NS). Logistic
      regression analysis showed age (OR: 1.04.1; 95% CI: 1.0-1.2; P=0.049) Killip
      class > or = 2 (OR: 4.6; 95% CI: 1.3-16.4; P=0.01) to be the only independent
      predictors of 6-month cardiac mortality. CONCLUSION: Systematic transfer of
      elderly STEMI patients for PPCI, with a door-to-balloon time <1 h, leads to
      clinical results similar to those achievable in patients who present directly in
      hospital with cath.-lab. facilities.

PMID- 18608034
TI  - Is there still a role for treatment with beta-adrenoceptor antagonists in post
      myocardial infarction patients with well-preserved left ventricular systolic
      function?
AB  - The utility of beta-adrenoceptor antagonists post myocardial infarction was
      established in the pre-thrombolytic era. Evidence for improvement in long-term
      prognosis with metoprolol, timolol and propranolol in particular derives from
      reduction in event rates in patients who have had substantial left ventricular
      damage at the time of infarction and probably correlates largely with the more
      recently demonstrated salutary effects of this group of drugs in patients with
      chronic heart failure. In all other respects, evidence for beneficial effects of
      beta-adrenoceptor antagonists in peri-infarct and post-infarct therapeutics is
      equivocal. They appear to exert no major influence on outcomes in patients with
      unstable angina, nor do they markedly alter early clinical course in
      uncomplicated acute myocardial infarction, irrespective of other interventions.
      Furthermore, the limited available analyses suggest no discernible beneficial
      effect on long-term outcomes post-uncomplicated infarction. It is possible that
      in such patients, current recommendations for 'routine' long-term beta
      adrenoceptor blockade can no longer be justified.

PMID- 18608035
TI  - Angiographic de novo appearance of a myocardial bridge after successful
      percutaneous transluminal coronary angioplasty.

PMID- 18608039
TI  - Successful percutaneous management of coronary dissection and extensive
      intramural haematoma associated with ST elevation MI.

PMID- 18608040
TI  - Dressler's syndrome following pulmonary vein isolation for atrial fibrillation.
AB  - Dressler's syndrome, characterized by features of fever, pericarditis and
      pericardial effusion typically occurs in the weeks to months following a
      myocardial infarction. The syndrome has also been described following several
      other myocardial and pericardial pathologies, including two reports of Dressler's
      syndrome following radio-frequency ablation. We describe a case of Dressler's
      syndrome following a pulmonary vein isolation procedure, which is being performed
      with increasing frequency as a treatment strategy for atrial fibrillation.

PMID- 18608041
TI  - The antiplatelet effect of atorvastatin in patients with acute coronary syndrome
      depends on the hs-CRP level.
AB  - BACKGROUND: In data we published earlier, there is a correlation between platelet
      aggregation in patients with acute coronary syndrome (ACS) who are receiving
      aspirin and elevated hsCRP-level. We suggested that antiplatelet action of
      statins, which are known to lower hsCRP-levels, could be especially pronounced in
      patients with high levels of hsCRP. METHODS AND RESULTS: 54 patients with ACS
      without ST-segment elevation were included in this study. All patients received
      aspirin 160-325 mg daily. In addition to aspirin, some patients received
      atorvastatin 40-80 mg/d (n=19) or 300 mg of clopidogrel followed by 75 mg/d
      (n=15). HsCRP-levels and ADP-induced platelet aggregation were assessed on the
      first and on the eight days of treatment. Patients were divided into subgroups
      according to initial hsCRP-levels and treatment. In atorvastatin/high-CRP
      subgroup, the level of aggregation was about three times lower after eight days
      than it was on the first day. In contrast, in atorvastatin/low-CRP subgroup the
      level of platelet aggregation did not change during the same period. The effect
      of clopidogrel did not depend on hsCRP-level. In control group (patients treated
      with aspirin alone), platelet aggregation did not change with time. CONCLUSION:
      There is a correlation between antiplatelet effect of atorvastatin and initial
      hsCRP-level. The antiplatelet effect of clopidogrel does not depend on hsCRP
      level.

PMID- 18608042
TI  - Risk prediction in acute coronary syndrome from serial in-hospital measurements
      of N-terminal pro-B-type natriuretic peptide.
AB  - There is limited information about the in-hospital plasma profile of N-terminal
      pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation
      acute coronary syndrome (NSTACS) and furthermore, the prognostic influence of the
      timing of NT-proBNP measurements in NSTACS is unsettled. These subject matters
      are elucidated in this study composed of 455 patients with NSTACS (symptoms <24
      h). NT-proBNP was measured at 0, 6, 12, 24, 36, 48, 72 and 96 h following
      admission. Any death was registered at follow-up (median: 2.3 years). The study
      demonstrated a monophasic profile of the plasma NT-proBNP values, reaching a
      maximum at 6 hours, and it showed an independent prognostic significance of NT
      proBNP irrespective of the sampling time. Risk prediction by NT-proBNP was
      improved by combining the baseline measurement and one value taken between 24 and
      96 h (at 48 h, P<0.001). No additional prognostic information was provided by
      including more than one late in-hospital NT-proBNP value. CONCLUSIONS: The in
      hospital NT-proBNP measurements exhibit a monophasic profile in patients with
      NSTACS and these values provide independent prognostic information as regards
      mortality irrespective of the sampling time. Moreover, risk prediction of NT
      proBNP is strengthened by combining the admission measurement with an additional
      value during the hospitalization.

PMID- 18608044
TI  - Adult age differences in attention to semantic context.
AB  - In three experiments age differences in attention to semantic context were
      examined. The performance of younger adults (ages 18-29 years) and older adults
      (ages 60-79 years) on a semantic priming task indicated that both age groups
      could use information regarding the probability that a prime and target would be
      related to flexibly anticipate the target category given the prime word
      (Experiment 1). The timing by which target expectancies were reflected in
      reaction time performance was delayed for older adults as compared to younger
      adults, but only when the target was expected to be semantically unrelated to the
      prime word (Experiment 2). When the target and prime were expected to be
      semantically related, the time course of priming effects was similar for younger
      and older adults (Experiment 3). Together the findings indicate that older adults
      are able to use semantic context and the probability of stimulus relatedness to
      anticipate target information. Although aging may be associated with a delay in
      the timing by which controlled expectancies are expressed, these findings argue
      against an age-related decline in the ability to represent contextual
      information.

PMID- 18608043
TI  - Comparison of four different cardiac troponin assays in patients with end-stage
      renal disease on chronic haemodialysis.
AB  - BACKGROUND: Several studies have documented the importance of troponin elevation
      as a prognostic marker in end-stage renal disease (ESRD). The reason for the
      elevated concentrations is not clarified. We do not know whether the different
      assays recognize the same patients within ESRD populations. The aim of this study
      was to compare concentrations of troponin measured by four different assays in a
      cohort of patients with ESRD, to investigate whether haemodialysis affects
      troponin concentrations, and to compare the prognostic potential of the different
      assays. METHODS: We included 109 patients on chronic haemodialysis. Serum cardiac
      troponin T (cTnT) was measured pre- and postdialysis using Elecsys 2010 and
      troponin I (cTnI) using Access AccuTnI, Dimension RxL and AIA-600II. RESULTS: The
      cTnT assay had the highest percentage of elevated concentrations for all chosen
      cut-offs with a reduction in percentage of patients with elevated concentrations
      during haemodialysis. Elecsys 2010 and AIA-600II demonstrated a significant
      increased mortality with raised concentrations of troponin. CONCLUSIONS: The
      diverging results in previous studies are most likely based on substantial
      differences in the analytical performance of the assays. The prognostic value of
      cTnT appears superior to cTnI, which amplifies the prognostic significance of
      this cardiovascular marker in patients with ESRD.

PMID- 18608045
TI  - Metabolic syndrome and cognitive function in healthy middle-aged and older adults
      without diabetes.
AB  - OBJECTIVE: Few studies have addressed whether the metabolic syndrome (MetS) and
      its individual components are associated with cognitive function in middle-aged
      and older populations, as well as whether specific areas of cognition are more
      affected than others. We examined the cross-sectional association between MetS
      and six areas of cognitive function in healthy cognitively intact adults without
      diabetes (n = 853, mean age 61 years) randomized in two intervention trials.
      METHODS: The National Cholesterol Education Program (NCEP) criteria were used to
      identify subjects with MetS. Cognitive function was assessed with a
      neuropsychological battery. A principal components analysis was used to extract
      five uncorrelated factors interpreted to represent five areas of cognition, and a
      measure of global cognition was calculated. RESULTS: MetS was weakly but non
      significantly associated with lower verbal learning (beta = -.14 [SE(beta) =
      0.09], p = .15). As the number of MetS criteria increased, scores on global
      cognition (p trend = .01), verbal learning (p trend = .06) and semantic memory (p
      trend = .04) decreased. Hypertension was the only MetS risk factor that was
      independently correlated with lower verbal learning (beta = -.17 [SE(beta) =
      0.08], p = .04), semantic memory (beta = -.26 [SE(beta) = 0.08], p = .001) and
      global cognition (beta = -.15 [SE(beta) = 0.07], p = .04). CONCLUSION: This study
      adds to the evidence of an association between MetS and lower cognitive function
      among healthy middle-aged and older adults without CVD and diabetes, as well as
      confirms the correlation between hypertension and lower cognition.

PMID- 18608047
TI  - Aging and working memory inside and outside the focus of attention: dissociations
      of availability and accessibility.
AB  - Two experiments used the N-Back task to test for age differences in working
      memory inside and outside the focus of attention. Manipulations of the difficulty
      of item-context binding (Experiment 1) and of stimulus feature binding
      (Experiment 2) were used to create conditions that varied in their demand on
      working memory, with the expectation that greater demand might increase age
      differences in focus-switching costs and the search rate outside the focus of
      attention. Results showed, however, that although age differences were evident in
      measures of overall speed and accuracy, and the manipulations significantly
      affected response times and accuracy in the expected direction, the experimental
      manipulations had no impact on age differences. Findings instead pointed to age
      related reductions in accuracy but not speed of focus-switching and search
      outside the focus of attention. Thus, age-related deficits appear to involve the
      availability of representations in working memory, but not their accessibility.

PMID- 18608048
TI  - Age-related differences in strategy knowledge updating: blocked testing produces
      greater improvements in metacognitive accuracy for younger than older adults.
AB  - Age-related differences in updating knowledge about strategy effectiveness after
      task experience have not been consistently found, perhaps because the magnitude
      of observed knowledge updating has been rather meager for both age groups. We
      examined whether creating homogeneous blocks of recall tests based on two
      strategies used at encoding (imagery and repetition) would enhance people's
      learning about strategy effects on recall. Younger and older adults demonstrated
      greater knowledge updating (as measured by questionnaire ratings of strategy
      effectiveness and by global judgments of performance) with blocked (versus
      random) testing. The benefit of blocked testing for absolute accuracy of global
      predictions was smaller for older than younger adults. However, individual
      differences in correlations of strategy effectiveness ratings and postdictions
      showed similar upgrades for both age groups. Older adults learn about imagery's
      superior effectiveness but do not accurately estimate the magnitude of its
      benefit, even after blocked testing.

PMID- 18608046
TI  - Exploring cognitive effects of self reported mild stroke in older adults:
      selective but robust effects on story memory.
AB  - Relatively little systematic information is available regarding patterns of
      cognitive effects of mild stroke in older adults. We explored this problem with a
      series of two independent samples from the Victoria Longitudinal Study data
      archives. In Study 1, self-reported mild stroke and neurologically intact matched
      controls were (a) confirmed as similar on a set of neurocognitive speed, basic
      cognition, and awareness indicators, and (b) compared for differences on a set of
      episodic, semantic, and working memory tasks. The mild stroke group was
      selectively worse on the language intensive story memory task. This effect was
      partially attributable to a deficit in remembering the most thematic information.
      Study 2 closely replicated these procedures and results. In addition, Study 2
      follow-up analyses, comparing provisional right-hemisphere damaged and left
      hemisphere damaged (LHD) participants, revealed that the thematic story memory
      deficit for mild stroke participants could be due to the selective impairment of
      LHD participants.

PMID- 18608049
TI  - Working memory for item and temporal information in younger and older adults.
AB  - Two experiments examined age differences in mechanisms hypothesized to affect
      activation of item and temporal information in working memory. Activation levels
      were inferred from the ability to reject n-back lures matching items in different
      temporal positions. Information with the least decay had a performance advantage
      over less recent information, but was susceptible to the same temporal context
      errors found in all adjacent-to-target lure positions. Lures most distant from
      the current item showed a performance rebound. The pattern of increased
      magnitudes of age effects at adjacent-to-target positions indicated a reduction
      in older adults' working memory for temporal context information above and beyond
      item memory declines. Results overall support the emphasis on context information
      as a critical factor in working memory and cognitive aging.

PMID- 18608050
TI  - Aging and stereotype suppression.
AB  - Recent work in social cognitive aging has suggested that older adults are more
      likely than younger adults to activate and use stereotypic information, even when
      they intend not to. Furthermore, evidence suggests that older adults have
      difficulty altering their interpretation of a situation, even when it has become
      clear that their initial interpretation is incorrect. In the current study,
      younger and older adults read a series of narratives in which a character had a
      sex-stereotyped occupation (e.g., a plumber is stereotypically male), and the
      character's gender was either consistent or inconsistent with that stereotype.
      Explicit labeling of gender was also varied. Results revealed that with explicit
      labeling, older adults were able to discount their stereotypes and avoid
      processing difficulties when subsequent stereotype-inconsistent information was
      encountered. These data suggest that when counter-stereotypic information is
      explicitly provided at encoding, older adults are no more likely than younger
      adults to rely on stereotypes, and are similarly capable of altering their
      interpretation of a situation when information suggests that interpretation is
      incorrect. These findings indicate that although older adults are more prone to
      the influence of unwanted stereotypes, this effect can be averted and judgments
      can be made more egalitarian by providing older adults with explicit stereotype
      contradiction at encoding.

PMID- 18608051
TI  - The influence of reduced visual acuity on age-related decline in spatial working
      memory: an investigation.
AB  - To investigate the relationship between visual acuity and cognitive function with
      aging, we compared low-vision and normally-sighted young and elderly individuals
      on a spatial working memory (WM) task. The task required subjects to memorise
      target locations on different matrices after perceiving them visually or
      haptically. The haptic modality was included as a control to look at the effect
      of aging on memory without the confounding effect of visual deficit. Overall, age
      and visual status did not interact to affect WM accuracy, suggesting that age
      does not exaggerate the effects of visual deprivation. Young participants
      performed better than the elderly only when the task required more operational
      processes (i.e., integration of information). Sighted participants outperformed
      the visually impaired regardless of testing modality suggesting that the effect
      of the visual deficit is not confined to only the most peripheral levels of
      information processing. These findings suggest that vision, being the primary
      sensory modality, tends to shape the general supramodal mechanisms of memory.

PMID- 18608052
TI  - Sensitivity of the informant questionnaire on cognitive decline: an application
      of item response theory.
AB  - The Informant Questionnaire on Cognitive Decline (IQCODE) is a formal informant
      report instrument, originally developed by Jorm and Jacomb (1989; Psychological
      Medicine, 19(4), 1015). The goal of the present study was to evaluate the range
      of cognitive decline in which the IQCODE is most sensitive, using item response
      theory (IRT). Existing data (N = 740) from a sample of community-dwelling older
      adults was used for this purpose. A 2-parameter model estimating item difficulty
      and discrimination fit the data best. Additionally, the IQCODE provided the most
      psychometric information in the range of -0.5 < theta < 1.5, with peak
      information obtained at approximately theta = 0.4. Based on individuals' latent
      score (theta) estimates, items on the IQCODE are adequate for use as a screening
      tool for dementia. Results of the item calibration may be useful for targeted
      assessment needs, such as the development of short forms.

PMID- 18608053
TI  - The role of men in women's acceptance of an intravaginal gel in a randomized
      clinical trial in Blantyre, Malawi: a qualitative and quantitative analysis.
AB  - Survey questionnaires and focus group discussions were used to investigate the
      association between a female participant's acceptance and her perception of her
      male partner's acceptance of an intravaginal gel as a prototype microbicide.
      Women who perceived their male partners would accept using the gel were more
      likely to highly accept the gel as compared to women who perceived their male
      partners would not accept using the gel (OR=24.57; 95%CI: 16.49-36.61).
      Qualitative analysis supported a positive association between female
      acceptability and perceived male partner acceptability. Qualitative research
      reiterated this finding and also found that men and women had different
      approaches to assess gel acceptability. Women integrated perceptions of their
      partner's acceptance into their own acceptability and reported their partners had
      positive experiences. In contrast, men reported a more neutral experience with
      the gel and assessed the gel without overt consideration of their partner's
      experiences. These results indicate that female perceptions of male partner
      acceptability and actual male partner acceptability need to be considered when
      addressing female-controlled product acceptability and use.

PMID- 18608054
TI  - The process of HIV status disclosure to HIV-positive youth in Kinshasa,
      Democratic Republic of the Congo.
AB  - As access to HIV/AIDS treatment increases in sub-Saharan Africa, greater
      attention is being paid to HIV-infected youth. Little is known about how HIV
      positive youth are informed of their HIV infection. As part of a larger formative
      study informing a treatment program in Kinshasa, Democratic Republic of the
      Congo, semi-structured interviews were conducted with 19 youth (10-21 years) who
      had previously been told their HIV status and 21 caregivers who had disclosed the
      youth's HIV status to the youth. Questions explored youth's and caregivers'
      experiences of and immediate reactions to disclosure. Youth's median age at
      disclosure was 15 years old, with a range of 10-18 years based on caregiver
      reports (n=21) and from 10-19 years based on youth reports (n=18). The most
      common reasons spontaneously given for disclosing were the child's adherence to
      their treatment regimen (5/16), the need of the child to protect her/himself or
      stay healthy (5/16), the child's increasing age (4/16) and so that the child
      would know why they are suffering (3/16). Most youth (16/19) were surprised to
      learn of their diagnosis; 50% (8/16) wondered about the infection's origins. A
      large majority felt that it is better for them to know their HIV status (88%;
      15/17). HIV care and treatment programs must be prepared to address the
      psychosocial needs of youth and their caregivers during the disclosure process.

PMID- 18608055
TI  - Ethnicity and sexual lifestyles among college students in a high-risk
      environment, Durban, South Africa.
AB  - The aim of the study is to examine the protective behavioural strategies used by
      college students in response to high levels of HIV infection, with a particular
      emphasis on ethnic variations. The data for the study are drawn largely from self
      completed questionnaires among college students in Durban. The results suggest
      that abstinence is most common protective factor among Indian and white students.
      However, among African students, abstinence is less common, particularly for men,
      despite the fact that concern about HIV is high in this group. Among the sexually
      active, the majority have more than one sexual partner. However, condom use among
      all sexually active students is high. Almost 70% reported using condoms at last
      sexual intercourse but consistent use remains elusive.

PMID- 18608056
TI  - Identification of primary HIV-1C infection in Botswana.
AB  - Methods for identification of primary HIV infections seem increasingly important
      to understand pathogenesis, and to prevent transmission, which is particularly
      efficient during acute infection. Most current algorithms for HIV testing are
      based on detection of HIV antibodies and are unable to identify early infections
      before seroconversion. The efficiency of prospective cohorts, which is a standard
      approach for identifying primary HIV-1 infection, depends on a variety of
      epidemiological and cultural factors including HIV incidence and stigma and, not
      surprisingly, varies significantly in different geographical areas. We report a
      voluntary counseling and testing (VCT)-based approach to identifying primary HIV
      1C infection that was developed as part of a primary HIV-1 subtype C infection
      study in Botswana. The referral strategy was based on: (1) collaboration with VCT
      centers at city clinics operated by the Ministry of Health; (2) partnering with
      the busiest non-government VCT center; (3) educating healthcare workers and the
      community about primary HIV infection; and (4) pairing with diverse VCT
      providers, including NGOs and private-sector organizations. Acute HIV-1
      infections were defined by a negative HIV-1 serology combined with a positive HIV
      1 RT-PCR test. Recent HIV-1 infections were identified by detuned EIA testing
      according to the classic STARTH algorithm. The VCT-based referral strategy
      resulted in the successful identification of 57 cases of acute and early HIV
      infection. A referral strategy of expanded VCT with viral RNA (Ribonucleic acid)
      testing to a national program in Botswana may be a promising approach for
      identification of primary HIV infections on a countrywide level. The program
      should offer VCT with viral RNA testing to the general public, facilitate proper
      counseling and risk reduction, and allow initiation of early HAART, and may
      reduce new viral transmissions.

PMID- 18608057
TI  - A randomized controlled study to evaluate the efficacy of an Internet-based
      intervention in reducing HIV risk behaviors among men who have sex with men in
      Hong Kong.
AB  - A randomized controlled study evaluated an Internet-based HIV behavioral
      intervention for men who have sex with men (MSM). Hong Kong Chinese men aged
      >or=18 having engaged in oral or anal MSM behaviors in the last six months were
      randomly allocated into the intervention (n=140) and the control groups (n=140).
      Participants were interviewed anonymously at the baseline and after six months.
      Interventions included periodic HIV information dissemination, monitoring of risk
      behaviors and interactive feedback, online peer counseling and provision of a
      hotline. The control group only received some educational materials. Efficacy of
      the intervention was not supported as no statistically significant between-group
      differences in background characteristics, HIV risk behaviors and perceptions
      were observed both at the baseline and after the 6-month period. Effectiveness of
      online interventions should not be taken for granted and evidence-based approach
      is warranted.

PMID- 18608058
TI  - Coping strategies of families in HIV/AIDS care: some exploratory data from two
      developmental contexts.
AB  - Caring for a family member with HIV/AIDS presents multiple challenges that strain
      a family's physical, economic and emotional resources. Family carers provide
      physical care and financial support and deal with changes in family relationships
      and roles, often with little support from outside of the family. Carers in
      developing countries face even greater challenges, due to lack of medical and
      support services, poverty and widespread discrimination against those with
      HIV/AIDS. Little is known about how family carers cope with these challenges or
      about the ways that development impacts on the process of coping. The current
      study explored coping strategies used by family carers in two contexts, Kerala,
      India and Scotland, UK. As part of a larger study, 28 family carers of persons
      living with HIV/AIDS were interviewed -23 in Kerala and 5 in Scotland. A modified
      version of the Ways of Coping scale was used to assess coping strategies.
      Responses were compared on the total number of coping responses used as well as
      on selected subscales of the WOC. Differences were assessed using the Mann
      Whitney U-test. The two cohorts differed significantly in terms of the coping
      strategies used. The carers from Scotland used a larger number of different
      coping strategies and scored higher on measures of problem focused coping,
      positive reappraisal, seeking social support, self-controlling and
      distancing/detachment. Respondents from Kerala scored higher on a measure of self
      blame. Results are discussed in terms of the impact of community resources on
      coping strategies.

PMID- 18608059
TI  - Bypassing non-adherence via PEG in a critically ill HIV-1-infected patient.
AB  - This case study describes a 44-year-old, chronically non-adherent, HIV-infected
      male with relapsing, life threatening toxoplasmic encephalitis (TE) and other
      recurring opportunistic infections. Non-adherence resulted in critical illness,
      suppressed CD4 lymphocyte count and elevated viral load. In order to bypass the
      patient's complete psychological aversion to taking medication, and after
      exhausting various psychological interventions, a percutaneous endoscopic
      gastronomy (PEG) tube was inserted for delivery of indispensable medication.
      During the 15-month follow-up the patient was adherent, exhibiting a consistently
      undetectable viral load, high CD4 count and a remission of the opportunistic
      infections. This is an interesting case study demonstrating life-saving and long
      term benefit of PEG in an exceptional setting, which has implications for future
      research and treatment of non-adherent HIV-infected patients.

PMID- 18608060
TI  - Rural Malawians' perceptions of HIV risk behaviors and their sociocultural
      context.
AB  - Prevention remains key in the fight against HIV/AIDS. However, prevention
      requires understanding the sociocultural and economic context in which HIV-risk
      behaviors occur. This qualitative, descriptive study was part of the initial
      phase of a larger project to adapt and test a community-based HIV-prevention
      intervention. We conducted individual interviews with rural Malawian community
      leaders and focus groups with adult community residents to elicit perceptions of
      both sexual and non-sexual HIV-risk behaviors and their sociocultural context.
      Interviews and focus groups were conducted in Chichewa, audio-taped, transcribed
      and translated into English by bilingual co-investigators. Content analysis of
      transcripts was done collaboratively by US-based and Malawian co-investigators to
      confirm culturally accurate interpretation of data. Participants identified
      sexual and non-sexual HIV-risk behaviors and contextual factors that influence
      these behaviors, including gender relations, cultural practices, economic
      conditions and religion. Community leaders and residents voiced similar
      perspectives on risk behaviors, except that community leaders were much less
      likely than residents to discuss sexual transmission through participation in
      traditional cultural practices. We incorporated these study results in adapting
      our HIV-prevention intervention to the sociocultural context of rural Malawi.
      Study participation enhanced the community leader's and resident's interest in
      the intervention phase of the project.

PMID- 18608061
TI  - Psychological distress and engagement in HIV-related services among individuals
      seeking mental health care.
AB  - In the US, HIV-related mental health care has been funded for its ability to help
      engage and retain individuals living with HIV into other components of HIV
      related care and treatment. However, little is known empirically about the types
      of HIV prevention and care with which they are, or need to be, connected. To
      explore this, data were collected from 617 individuals upon their self-enrollment
      in HIV-related mental health care in a large US city with high rates of HIV
      infection. Nearly a third of the participants (n=195) were "minimally engaged" in
      care services, 53% were "moderately engaged" and 15.6% were "highly engaged".
      There were significant differences between level of care engagement according to
      one's ethnicity, X(2)(4, n=617)=38.05; p<.001; Cramer's V=.18, with African
      Americans and Latinos more likely to be highly engaged in care services compared
      to their Caucasian counterparts. Furthermore, individuals who were highly engaged
      in services had significantly lower levels of depression than their less engaged
      peers, F(2, 614)=8.18; p<.001; eta(2)=.03. Results suggest that while ethnic
      minorities were engaged in a higher number of care services, they were enrolling
      in mental health care following enrollment in other care services. Given the
      numerous benefits of engaging in HIV-related mental health early in the course of
      infection, it is important that case managers and primary care physicians educate
      African-Americans and Latinos on the benefits of mental health care in order to
      facilitate earlier engagement in HIV-related mental health services.

PMID- 18608062
TI  - Trauma, anxiety and reported health among HIV-positive persons in Tanzania and
      the US Deep South.
AB  - Little research has been conducted in less wealthy nations to evaluate the
      prevalence of severe life traumas in general population groups and the impact of
      such traumas. Previous studies in wealthy nations have found that experiencing
      severe traumas can cause elevated levels of anxiety, but few studies have
      examined this association in non-disaster situations in less wealthy nations.
      Trauma and trauma-related anxiety are associated with greater sexual risk taking
      behaviours, lower HIV medication adherence levels and poorer health outcomes in
      wealthy nations. The objectives of this manuscript are: (1) to compare rates of
      trauma in two HIV-positive samples from areas that have not experienced disaster
      situations that are recognized by the international community as traumatic
      events; and (2) to examine whether the reported traumatic experiences are
      similarly associated with self-reported mental and physical health. The samples
      come from a region of a wealthy nation that consistently experiences large
      increases in incident AIDS cases and where the epidemic is largely transmitted
      heterosexually (Deep South, United States; n =611) and a region in a less wealthy
      nation with relatively high HIV prevalence and incidence rates and where
      transmission is also primarily heterosexual (Moshi, Tanzania; n =72). Compared to
      the US sample, the Tanzanian sample reported significantly higher rates of trauma
      in the areas of illness, injury, accidents and "other" significant traumas, a
      higher prevalence of anxiety and poorer physical health. The experience of trauma
      was similarly associated with greater mental health symptomatology and poorer
      physical health in both samples. Further investigation into the area of trauma
      and its sequelae is warranted, particularly in relation to risk behaviours and
      HIV medication adherence. At a time of increasing anti-retroviral therapy (ART)
      availability in less wealthy nations, additional focus on trauma care could
      improve ART adherence rates and reduce risk behaviors, thereby assisting in
      stemming the further spread of the epidemic.

PMID- 18608063
TI  - Moderate intensity exercise training reverses functional aerobic impairment in
      HIV-infected individuals.
AB  - HIV infection and HIV drug therapies result in physical and psychological
      challenges to those living with HIV. These conditions contribute to decreased
      functional aerobic capacity (FAC). The aim of this study was to determine the
      effects of a combined moderate-intensity aerobic and resistance exercise
      intervention on the FAC of HIV-infected individuals. Forty HIV-infected
      individuals were randomized to an exercise group (EX) who completed six weeks of
      moderate-intensity exercise training, or to a control group (CON) that did not
      receive the exercise intervention. Twice weekly, the EX group completed 30
      minutes of moderate-intensity aerobic training followed by moderate-intensity
      resistance training. Prior to, and following, the intervention the FAC for each
      subject was determined by graded exercise treadmill stress test (GXT). At
      baseline testing, the mean FAC as determined by treadmill time-based estimation
      of maximal oxygen consumption was 25% below age-predicted values, a level of
      reduction indicating the presence of functional aerobic impairment (FAI).
      Following the intervention, the EX had a significant increase in time to fatigue
      and estimated VO(2) max (p<.001). Further, FAI was eliminated (1% above age
      predicted values) during the exercise training. The EX group also experienced
      decreased heart rates during Stages 1 (p=.02), 2 (p=.01), 4 (p=.05) and 6 (p=.02)
      of the GXT. The CON had no significant changes during the intervention period.
      These data indicate that six weeks of combined moderate-intensity aerobic and
      resistance training can improve FAC and eliminate FAI in those with HIV. Results
      suggest that the functional limitations common in HIV-infected individuals are
      due in part to detraining that is reversible through moderate exercise adherence.

PMID- 18608064
TI  - Gender differences in health status and care among HIV-infected minority drug
      users.
AB  - Gender differences were examined in health status and HIV care among HIV-infected
      minority drug users. More women than men reported having HIV-related symptoms and
      other health conditions, such as asthma and allergies. Hepatitis B or C was more
      often reported by men. As compared to men, women delayed HIV care and fewer
      attended HIV support groups. Delayed entry into HIV treatment was also
      significantly related to being Hispanic and being diagnosed with HIV in the pre
      HAART era. No significant gender difference was found in current use of HIV
      medications. Use of HIV medications was significantly related to being married,
      no history of childhood sexual abuse, enrollment in an HIV clinic and attending
      HIV support groups. The findings demonstrate the importance of family and social
      support for HIV-positive drug users and also suggest a need for special attention
      to those who have childhood sexual abuse experience.

PMID- 18608065
TI  - Drug use and weight loss in HIV-infected Hispanic men.
AB  - Weight loss is an independent risk factor for mortality in HIV but the role of
      drug use in HIV-related weight loss is not well described. We conducted this
      study to determine the role of drug use in HIV-related weight loss. Men (n=304),
      all of whom were Hispanic, were recruited into one of three groups: HIV-infected
      drug users; HIV-non-infected drug users; and HIV-infected non-drug users. Body
      mass index (BMI) was measured at successive visits. The groups were re
      categorized based on self-reported drug use at the current visit into: (1) users
      of cocaine alone; (2) users of cocaine and opiates; (3) users of opiates alone;
      (4) former drug users; and (5) those who denied ever using drugs (all HIV
      infected). The effect on BMI of the duration of use of the specific drug types
      was evaluated using repeated-measures analyses. Longer duration of exclusive
      opiate use or mixed cocaine and opiate use did not affect BMI in the men,
      regardless of HIV status. Exclusive cocaine use was associated with a decline in
      BMI among HIV-infected men (-0.070 kg/m(2) per month duration of use; SE=0.033;
      p=0.037) but not among HIV-uninfected men (0.024 kg/m(2) per month; SE=0.023;
      p=0.29). Adjustment for marijuana, cigarette and alcohol use in all men, or for
      CD4 count, viral load or HIV medication use in the HIV-infected men, did not
      alter the conclusions. We conclude that the use of opiates or combined opiates
      and cocaine does not increase the risk of weight loss in the presence or absence
      of HIV infection. Exclusive cocaine use may exacerbate weight loss in HIV
      infection.

PMID- 18608066
TI  - Targeting AIDS orphans and child-headed households? A perspective from national
      surveys in South Africa, 1995-2005.
AB  - In the HIV and AIDS sphere, children remain on the margins with respect to
      advocacy, prevention, treatment and care. Moreover, concern is generally limited
      to specific categories of children, most especially children living with HIV,
      orphaned children and child-headed households. Excluded from view are the very
      large numbers of children affected by generalized HIV/AIDS epidemics, now in
      advanced stages, in already impoverished countries in southern Africa. In this
      paper, we use information from comparable national household surveys in South
      Africa, in five waves between 1995 and 2005, to examine the impact of HIV and
      AIDS on children and on the structure of the households in which they find
      themselves. The question posed is whether it is appropriate to target orphans and
      child-headed households in this context. The data indicate that orphaning,
      particularly loss of a mother, tripled during this period, as is to be expected
      from rising adult mortality. Though they remain a small proportion, child-only
      households also rose markedly during this time. However, difficult as their
      situation is, neither orphans nor child-only households appear to be the worst
      off children, at least from the point of view of reported sources of financial
      support and per capita monthly expenditure. Households headed by single adults
      and young adults are economically vulnerable groups not yet included in efforts
      to support affected children and families. Poverty is a pitiless backdrop to the
      AIDS epidemic and needs to be at the heart of strategies to address the needs of
      all vulnerable children in hard-hit communities.

PMID- 18608067
TI  - Stigma and discrimination experiences of HIV-positive men who have sex with men
      in Cape Town, South Africa.
AB  - Since the primary mode of HIV transmission in sub-Saharan Africa is heterosexual,
      research focusing on the sexual behaviour of men who have sex with men (MSM) is
      scant. Currently it is unknown how many people living with HIV in South Africa
      are MSM and there is even less known about the stigmatisation and discrimination
      of HIV-positive MSM. The current study examined the stigma and discrimination
      experiences of MSM living with HIV/AIDS in South Africa. Anonymous venue-based
      surveys were collected from 92 HIV-positive MSM and 330 HIV-positive men who only
      reported sex with women (MSW). Internalised stigma was high among all HIV
      positive men who took part in the survey, with 56% of men reporting that they
      concealed their HIV status from others. HIV-positive MSM reported experiencing
      greater social isolation and discrimination resulting from being HIV-positive,
      including loss of housing or employment due to their HIV status, however these
      differences were not significant. Mental health interventions, as well as
      structural changes for protection against discrimination, are needed for HIV
      positive South African MSM.

PMID- 18608069
TI  - Test-retest evaluation of HAT-QoL and SF-36 in an HIV-seropositive sample.
AB  - We sought to correct previously reported psychometric and content problems of the
      HIV/AIDS-Targeted Quality of Life Instrument (HAT-QoL) and to assess test-retest
      reliability of this revised HAT-QoL as well as the MOS 36-Item Short-Form Health
      Survey (SF-36) when used in an HIV-seropositive outpatient sample. A total of 153
      participants randomly sampled from an HIV specialty and general medical clinics
      completed a test booklet that contained HAT-QoL and the SF-36; a random subsample
      of 60 participants were asked to return in approximately two weeks to complete
      the instruments again. Using the baseline sample, internal consistency
      coefficients of all final HAT-QoL dimensions were > or =0.80. The retest
      subsample, for which there were no significantly different characteristics than
      the baseline sample, completed the instruments again an average of 14.7 days
      after baseline completion. For HAT-QoL, only one (Provider Trust) of the nine
      dimensions revealed a significant test-retest difference (+5.9, p=0.05). All HAT
      QoL intraclass correlation coefficients (ICCs) were > or =0.64 (seven values were
      > or =0.73). All effect sizes were small. For SF-36, two dimensions (Physical
      Functioning and Social Functioning) revealed significant test-retest differences,
      and one dimension (Mental Health) revealed a difference approaching significance
      (p=0.06). The SF-36 ICCs were similar to those for HAT-QoL, with the exception of
      three dimensions--Vitality, Role-Emotional and Mental Health (all were<0.56).
      Though most effect sizes were small, Social Functioning and Mental Health
      estimates were approaching more moderate effect sizes. HAT-QoL reveals
      considerable short-term stability and has psychometric features in the
      seropositive population comparable to instruments such as SF-36, while obtaining
      unique information.

PMID- 18608068
TI  - HIV vaccine acceptability among immigrant Thai residents in Los Angeles: a mixed
      method approach.
AB  - This study examined HIV vaccine acceptability among immigrant Thai residents in
      Los Angeles, California. We combined a qualitative research method (focus groups)
      with an innovative market research method (conjoint analysis). Focus groups
      explored social issues, concerns, barriers and motivators associated with HIV
      vaccine acceptability. Conjoint analysis was used to assess preferences among
      eight hypothetical HIV vaccines with varying attribute profiles and the impact of
      various attributes on acceptability. Five main themes were identified in the
      focus groups regarding acceptance and utilization of preventive HIV vaccines: (1)
      vaccine characteristics, such as efficacy, physical side-effects and cost, (2)
      fear of a vaccine, (3) vaccine acceptability and optimism, (4) social and family
      responses and (5) behavioral disinhibition. Conjoint analysis revealed HIV
      vaccine acceptability ranging from 7.4 (SD = 19.4) to 85.2 (SD = 24.3) across
      eight hypothetical vaccines. The vaccine with the highest acceptability had the
      following attributes: 99% efficacy, no side-effects, 10 years of protection,
      protects against one sub-type, free, one dose and given by injection. Vaccine
      efficacy had the greatest impact on acceptability (51.4, p=.005), followed by
      side-effects (11.1, p=.005) and duration of protection (8.3, p=.005). Despite
      some apprehensions and concerns, Thai residents perceived an HIV vaccine as
      making an important contribution to society and to protecting oneself and one's
      family from HIV infection. Nevertheless, acceptability of a partially efficacious
      vaccine may be low, suggesting the need for tailored social marketing
      interventions that might emphasize a collectivistic rather than an
      individualistic focus. Assessing HIV vaccine acceptability using a mixed-method
      approach is feasible with Thai residents and should lend itself to HIV vaccine
      research with other Asian Pacific Islander populations in the US.

PMID- 18608070
TI  - Decisions to participate in research: views of underserved minority drug users
      with or at risk for HIV.
AB  - Under-representation of minority populations, particularly African Americans, in
      HIV/AIDS research is problematic because African Americans bear a greater disease
      burden from HIV/AIDS. Studies of motivations for participating in research have
      emphasized factors affecting individuals' willingness to participate and barriers
      to participation, especially in regard to HIV vaccine research. Little is known
      about how underserved minority drug users perceive research and their decisions
      to participate. This study describes African American drug users' perceptions of
      research participation and their decisions to participate based on three kinds of
      hypothetical HIV/AIDS-related clinical studies. In-depth, qualitative interviews
      were conducted with 37 underserved, African American crack cocaine users,
      recruited from participants already enrolled in three different behavioral HIV
      prevention studies. Interviews were recorded, transcribed, coded for themes and
      sub-themes and analyzed using directed and conventional content analysis.
      Participants' decisions to take part in research often involved multiple
      motivations for participating. In addition, decisions to participate were
      characterized by four themes: a desire for information; skepticism and mistrust
      of research and researchers; perceptions of medical care and monitoring within a
      study; and participant control in decisions to participate or decline
      participation. Lack of adequate information and/or medical care and monitoring
      within a study were related to mistrust, while the provision of information was
      viewed by some individuals as a right and acknowledgement of the participant's
      contribution to the study. Participants perceived, rightly or wrongly, that
      medical monitoring would control some of the risks of a study. Participants also
      described situations of exerting control over decisions to enter or withdraw from
      a research study. Preliminary findings suggest that continuous communication and
      provision of information may enhance enrollment and adherence. Further
      exploration of decisions to participate in research will add to the understanding
      of this complex phenomenon and enhance the ability of individuals with HIV/AIDS
      to benefit from research.

PMID- 18608071
TI  - Sexual behavior, fertility desires and unmet need for family planning among home
      based care clients and caregivers in Kenya.
AB  - As antiretroviral treatment becomes more available, community home-based care
      (CHBC) clients may begin to resume normal daily activities including the
      resumption of sexual relationships. This study examines sexual behavior,
      contraceptive use, unmet need for family planning and attitudes toward pregnancy
      in the context of HIV among CHBC participants (clients and caregivers), many of
      whom are HIV-positive or at risk for HIV, of the COPHIA project in Kenya. The
      COPHIA project was implemented by Pathfinder International with support from
      USAID/Kenya. We interviewed 171 CHBC clients and 183 CHBC caregivers and
      conducted four focus groups with caregivers. Data were collected from randomly
      selected COPHIA-affiliated CHBC programs in Western Province and in Nairobi
      between September and November 2004. Forty-four percent of clients and 55% of
      caregivers had been sexually active in the past six months. The reproductive
      health needs of this population are complex; a significant percentage of study
      participants have an unmet need for family planning and some desire more
      children. A small proportion of study participants were pregnant during the time
      of the interview. The majority of those who use contraception reported relying
      solely on the male condom to prevent pregnancy. While vital for HIV prevention
      and easily distributed by CHBC programs, the male condom is not as effective as
      other methods in preventing pregnancy. Community home-based care program
      participants need counseling related to contraception, fertility desires and
      pregnancy. The promotion of dual method use is crucial to this population.
      Besides referring participants to family planning services, CHBC programs need to
      consider how and if they can meet the family planning and other reproductive
      health needs of their participants.

PMID- 18608072
TI  - Late diagnosis of HIV infection at two academic medical centers: 1994-2004.
AB  - Over the last decade, there has been increased attention to the role of earlier
      HIV testing in the United States. Our objective was to determine if this has
      translated into changes in the proportion of inpatients with advanced disease at
      the time of initial HIV diagnosis. We identified inpatients discharged with a new
      diagnosis of HIV infection or AIDS between 1994 and 2004 at two academic medical
      centers. We examined trends in initial CD4 count at diagnosis over three time
      periods: 1994-1996, 1997-2000 and 2001-2004. Between 1994 and 2004, 235
      inpatients were newly diagnosed with HIV infection or AIDS in the two centers.
      For the 217 patients with available CD4 count data, the median initial CD4 count
      was 41/microl (interquartile range 19-138/microl). Of the 217 patients, 184(85%)
      had CD4 < or =200/microl and 119/217 (55%) had CD4 < or =50/microl. There were no
      significant differences in median CD4 count by time period. A large majority of
      inpatients with newly diagnosed HIV infection at two academic medical centers
      between 1994 and 2004 had signs of advanced immunodeficiency. Over this recent 11
      year period there was no evidence that inpatients with a new HIV diagnosis were
      identified at earlier stages of disease.

PMID- 18608073
TI  - Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected
      women.
AB  - Among women with HIV infection, pregnancy is a time when maintenance of maternal
      health and reduction of vertical HIV transmission are primary concerns. Few
      studies have examined adherence to Antiretroviral Treatment (ART) during
      pregnancy and in the postpartum period when the demands of childcare may
      significantly interfere with women's self-care behaviors. This study examined ART
      use and adherence in HIV-infected pregnant and postpartum women participating in
      the Women and Infants Transmission Study (WITS-IV) in the US. Adherence was
      assessed through a self-report interview during the third trimester of pregnancy
      and six-month postpartum. Data were also collected on demographics, biomedical
      markers and health related symptoms. During the third trimester visit, 77%
      (309/399) of women completed the self-report adherence measure; 61% (188/309)
      reported complete adherence. Factors associated with non-adherence included
      advanced HIV disease status, higher HIV-RNA viral load, more health-related
      symptoms and alcohol and tobacco use. At six-month postpartum, 55% (220/399)
      completed the measure; 44% (97/220) of these women reported complete adherence.
      Factors associated with non-adherence during the postpartum period were
      ethnicity, more health-related symptoms and WITS clinical site. Results of
      multivariate analyses using Generalized Estimated Equation analyses across the
      two visits revealed that more health-related symptoms, higher HIV-RNA viral load,
      increased alcohol use and clinical site were independently associated with ART
      non-adherence. These analyses indicate that medication adherence is more likely
      during pregnancy than postpartum in HIV-infected women, perhaps provoked by
      motivation to reduce vertical transmission and/or intensive antepartum
      surveillance. Further investigation is warranted to clarify factors implicated in
      women's decision-making process regarding ART medication adherence.

PMID- 18608074
TI  - Repeated pregnancy among women with known HIV status in Pune, India.
AB  - HIV-positive women of reproductive age face challenges in decision making related
      to pregnancy. Understanding factors influencing repeat pregnancies in women with
      known HIV status are necessary to guide interventions and counseling strategies
      to better inform and support them. We compared three groups of women attending a
      large antenatal clinic in Pune, India. They include: Group A--63 HIV-positive
      women coming for care for a repeat pregnancy after being diagnosed in a previous
      pregnancy; Group B--64 HIV-negative (repeat) pregnant women attending this
      antenatal clinic; and Group C--63 HIV-positive non-pregnant women currently
      enrolled in an ongoing clinical trial. Comparisons of Group A and B indicate that
      the likelihood of unplanned repeat pregnancies was significantly higher in HIV
      positive (70%) than HIV-negative (36%) women (OR=4.1, CI: 2.0-8.7). Inability to
      terminate the pregnancy (31%) and familial obligations (40%) appear to be
      important for continuing the unplanned repeat pregnancy. Despite high reported
      contraceptive use by HIV-positive women, pregnancies still occurred. Death of
      their youngest child is an important factor as 21% of HIV-positive pregnant women
      lost their youngest child compared with 3% of HIV-negative women and 3% of HIV
      positive non-pregnant women (p<0.001). Repeat pregnancies were more likely to
      occur for women who did not disclose their HIV status to their spouse. Thus the
      majority of the repeat pregnancies for HIV-positive women were both unplanned and
      unwanted.

PMID- 18608075
TI  - Assessing self-care component of activities and participation domain of the
      international classification of functioning, disability and health (ICF) among
      people living with HIV/AIDS.
AB  - Disability experience of persons with HIV illness has shifted from issues related
      to physical well-being to those concerning performance of daily life activities.
      This study aimed to find out the nature of self-care among people living with
      HIV/AIDS (PLWHA) in rural tertiary care center. The objectives were to determine
      reported self-care by performance qualifier of PLWHA and to find out reported
      self-care by capacity qualifier of PLHIV. A cross sectional study was conducted
      among the 194 PLHIV in rural tertiary care hospital. The Self-Care (d5) component
      of Activities and Participation domain (d) of the International Classification of
      Functioning, Disability and Health (ICF) was used. Among the 194 PLHIV patients
      studied, 82% were male. The average age was 36.87 years (SD+/-9.01) with a median
      of 35 years, varying from 15 to 65 years. Over 65% of the study group experienced
      one or more impairments. As HIV disease has become a more lifelong,
      unpredictable, but medically manageable condition, there is a need for more
      collaboration with other disability groups in order to identify commonalities in
      their experiences and to share collective concerns.

PMID- 18608076
TI  - Impact of lipoatrophy on quality of life in HIV patients receiving anti
      retroviral therapy.
AB  - Metabolic and morphological side-effects occur in HIV-infected individuals
      receiving anti-retroviral treatment (ART). Peripheral fat loss that occurs
      particularly in the face, limbs and/or buttocks is referred to as lipoatrophy and
      has been found to be highly stigmatizing and to adversely impact the health
      related quality of life (HRQL). Consumer Health Sciences Survey data collected
      between November 2003 and January 2006 were utilized to evaluate the impact of
      lipoatrophy on the HRQL in HIV-infected individuals receiving ART. This was
      evaluated using analysis of variance with item scores and mental component
      summary (MCS) and physical component summary (PCS) scores from the Medical
      Outcomes Trust questionnaire, SF-8 as dependent variables and lipoatrophy as the
      independent variable controlling for baseline age, sex and ethnicity. Clinical
      meaningfulness (mean difference divided by population standard deviation,
      delta/sigma) of differences between the groups with and without lipoatrophy was
      also evaluated. A cohort of 1124 subjects with at least six months of ART was
      selected based on the availability of data on whether or not lipoatrophy was
      present. Subjects were primarily male (80%), between the ages of 30 and 60 years
      (90%), Hispanic (37%) and about 25% each of African American and White. Overall,
      prevalence of lipoatrophy in this cohort of HIV patients was 18.9%. Statistically
      significant (p<0.001) differences in quality of life (as measured by SF-8
      individual item scores and MCS and PCS scores) were observed between the two
      groups. The differences between the groups in item and summary scores were
      clinically meaningful in the small to near medium range (0.28-0.43). HIV-infected
      patients already experience a considerable deficiency in HRQL compared to general
      population; this study demonstrates that lipoatrophy further enhances that
      negative impact on HRQL.

PMID- 18608077
TI  - Triply-diagnosed patients in the HIV/AIDS Treatment Adherence, Health Outcomes
      and Cost Study: patterns of home care use.
AB  - Although AIDS is a chronic illness, little is known about the patterns and
      correlates of long-term care use among triply diagnosed HIV patients. We examined
      nursing and home care use among 1,045 participants in the HIV/AIDS Treatment
      Adherence, Health Outcomes and Cost Study, a multi-site study of HIV-positive
      patients with at least one mental health and one substance disorder. Patient
      interviews and medical record review data were used to examine the average
      monthly cost of nursing home, formal home and informal home care. Multinomial
      logit and two-part regression models were used to identify correlates of the use
      of formal and informal home care and the number of informal home care hours used.
      During the three months prior to baseline, 2, 7 and 23% of participants used
      nursing home, formal home and informal home care, respectively. Patients who were
      better-educated, had higher incomes, had Medicaid insurance (with or without
      Medicare coverage) and whose transmission mode was homosexual sex had higher
      regression-adjusted probabilities of receiving any formal home care; Latinos and
      physically healthier patients had lower probabilities. Women and patients who
      abused drugs or alcohol (but not both) were more likely to receive informal care
      only. Overall, patients who were female, better-educated, physically or mentally
      sicker or single-substance abusers were more likely to receive any home care
      (either formal or informal), while those contracting HIV through heterosexual sex
      were less likely. Women received 28 more monthly hours of informal care than men
      and married patients received 31 more hours than unmarried patients. We conclude
      that at least one mutable policy factor (Medicaid insurance) is strongly
      associated with formal home care use among triply diagnosed patients. Further
      research is needed to explore possible implications for access among this
      vulnerable subpopulation.

PMID- 18608078
TI  - Complementary and alternative medicine use among HIV-positive people: research
      synthesis and implications for HIV care.
AB  - Use of complementary and alternative medicine (CAM) is prevalent among HIV
      positive individuals despite the success of antiretroviral treatments and limited
      evidence of CAM's safety and efficacy. To characterize the potential impact of
      CAM use on HIV care, we conducted a systematic review of 40 studies of CAM use
      among HIV-positive people. The goals of this review are to: (1) describe the
      demographic, biomedical, psychosocial and health behavior correlates of CAM use;
      (2) characterize patient-reported reasons for CAM use; and (3) identify
      methodological and conceptual limitations of the reviewed studies. Findings
      confirm that a high proportion of HIV-positive individuals report CAM use
      (M=60%). Overall, CAM use is more common among HIV-positive individuals who are
      men who have sex with men (MSM), non-minority, better educated and less
      impoverished. The use of CAM is also associated with greater HIV-symptom severity
      and longer disease duration. HIV-positive CAM users commonly report that they use
      CAM to prevent or alleviate HIV-related symptoms, reduce treatment side-effects
      and improve quality of life. Findings regarding the association between CAM use,
      psychosocial adjustment and adherence to conventional HIV medications are mixed.
      While the reviewed studies are instrumental in describing the characteristics of
      HIV-positive CAM users, this literature lacks a conceptual framework to identify
      causal factors involved in the decision to use CAM or explain implications of CAM
      use for conventional HIV care. To address this concern, we propose the use of
      health behavior theory and discuss implications of review findings for HIV care
      providers.

PMID- 18608080
TI  - A meta-analysis of disclosure of one's HIV-positive status, stigma and social
      support.
AB  - This study provides an analysis of the relationships among perceived stigma,
      reported disclosure and perceived social support for those living with HIV. The
      meta-analytic summary of 21 studies (4,104 participants) showed, as predicted, a
      positive, heterogeneous correlation between disclosure and social support (r =
      .159), a negative, heterogeneous correlation between stigma and social support (r
      = -.344) and a negative, homogenous correlation between stigma and disclosure (r
      = -.189). The heterogeneity of the first two relationships indicates the presence
      of moderators, which may include participants' age and publications' year.

PMID- 18608079
TI  - Trauma, stressful life events and depression predict HIV-related fatigue.
AB  - Despite the fact that fatigue is a common and debilitating symptom among HIV
      infected persons, we know little about the predictors of fatigue in this
      population. The goal of this cross-sectional study was to examine the effects of
      early childhood trauma, recent stressful life events and depression on intensity
      and impairment of fatigue in HIV, over and above demographic factors and clinical
      characteristics. We studied 128 HIV-infected men and women from one southern
      state. The median number of childhood traumatic events was two and participants
      tended to have at least one moderate recent stressful event. Multiple regression
      findings showed that patients with less income, more childhood trauma, more
      recent stressful events and more depressive symptoms had greater fatigue
      intensity and fatigue-related impairment in daily functioning. Recent stresses
      were a more powerful predictor of fatigue than childhood trauma. None of the
      disease-related measures (e.g. CD4, viral load, antiretroviral medication)
      predicted fatigue. Although stress and trauma have been related to fatigue in
      other populations, this is the first study to examine the effects of traumatic
      and recent stressful life events on fatigue in an HIV-infected sample.

PMID- 18608081
TI  - HIV voluntary counseling and testing: an experience from India.
AB  - Despite proof of voluntary counseling and testing (VCT) effectiveness in HIV
      disease prevention and management, there are limited reports on experience with
      pre- and post-HIV-test counseling in developing countries. In view of this, we
      aimed to bring to the fore the voluntary counseling and testing experience at a
      tertiary healthcare center. The present study was conducted at the voluntary
      counseling and testing center of a tertiary healthcare center and the National
      HIV Reference Center. Participants were 1169 men and 581 females attending the
      VCT clinic from February 2005 to March 2006. Odds ratios were calculated for each
      of the variable to analyze the strength of association with HIV sero-status. Out
      of 1750 patients, 322 (27.5%) males and 156 females (26.9%) tested HIV-positive.
      HIV-sero-positivity was observed to be associated to participant age
      (approximately 1.5 for 25-44 yrs age group), marital status (2.3 times in married
      patients), primary or lower education level (1.5 times), citing spouse death/HIV
      infected spouse as the reason for seeking VCT (2.2 times) and reporting a history
      of risk behavior as reason for getting tested. This study aims to evaluate the
      effectiveness of existing client initiated voluntary counseling and testing
      facility in the light of a recent recommendation by WHO/UNAIDS for the
      implementation of provider initiated voluntary counseling services. Through this
      study, we could also highlight socio-demographic factors, like education and age,
      and reasons stated by participants for seeking VCT, which were associated with
      HIV-positive status and put an individual at a higher risk of HIV infection.

PMID- 18608082
TI  - Clients' perspectives on HIV/AIDS care and treatment and reproductive health
      services in South Africa.
AB  - Qualitative research was conducted with HIV-positive women and men of
      reproductive age attending HIV/AIDS care and treatment services at a public
      health clinic in Cape Town, South Africa. Focus group discussions were held with
      women (n = 4) and men (n = 4), and in-depth interviews were held with four men to
      explore perceptions and experiences of HIV/AIDS care and treatment and sexual and
      reproductive health (SRH) care. Respondents praised their HIV/AIDS care and
      treatment, reflected on how it improved their quality of life and contrasted this
      with suboptimal care at other public health facilities, including SRH services.
      Women wanted integrated services, especially for contraception and to reduce
      stigma. HIV-positive men's lack of experience with SRH services and antipathy
      towards attending "women's" health services were highlighted. Challenges to
      involving men in HIV/AIDS care and treatment and SRH services and measures to
      address this were identified.

PMID- 18608083
TI  - A national survey of home-based care kits for palliative HIV/AIDS care in South
      Africa.
AB  - The objective of this study was to assess home-based care (HBC) kits and programs
      in South Africa to evaluate the feasibility of scaling up kit production and
      distribution. South African HBC organizations received structured questionnaires;
      key informant interviews and a literature review were completed to assess systems
      for production, distribution and supply of HBC kits. Meetings with stakeholders
      were held in two Provinces to share and analyze the study findings. The study
      team distributed questionnaires to 466 organizations and conducted interviews
      with representatives from 45 organizations, the Provincial Department of Health
      (DoH) and manufacturers of kits. All identifiable HBC organizations in South
      Africa were included in the survey. As a result 215 HBC organizations returned
      questionnaires; including non-governmental organizations (56%), community-based
      organizations (32%) and organizations affiliated with government health
      departments. Two types of kits were available: a home kit and a professional kit.
      The demand for HBC kits exceeded availability, kit contents and availability
      varied considerably and the supply chain was irregular. Kit production and
      distribution systems were fragmented. Replenishment of kit items was problematic.
      End-users are mostly caregivers who have not received adequate training on their
      use. The study shows that substantial work has been done by HBC organizations in
      South Africa to respond to the need for palliative care supplies within resource
      constraints. The growing demand for kits exceeds the supply. There is a need to
      improve the supply chain management of HBC kits, strengthen referral systems and
      links between community-based organizations and government departments, expand
      training opportunities for care givers, and develop monitoring and evaluation
      systems.

PMID- 18608085
TI  - Reasons for and against maternal HIV disclosure to children and perceived child
      reaction.
AB  - This study explores the decision making of 66 HIV-positive women regarding
      disclosing their serostatus to their children and the child's perceived immediate
      and long-term reactions. Data came from a larger investigation of the disclosure
      process of HIV-infected women. Children included 27 boys and 39 girls between the
      ages 5 and 18 years. Forty-one children knew of their mother's diagnosis and 32
      were disclosed to by their mother. Results suggest that women are interested in
      taking a leading role in disclosing to their children and make the decision based
      on the child's ability to handle the information and not be psychologically
      harmed.

PMID- 18608084
TI  - Measuring fatigue in people living with HIV/AIDS: psychometric characteristics of
      the HIV-related fatigue scale.
AB  - In the era of life-prolonging antiretroviral therapy, chronic fatigue is one of
      the most prevalent and disabling symptoms of people living with HIV/AIDS, yet its
      measurement remains challenging. No instruments have been developed specifically
      to describe HIV-related fatigue. We assessed the reliability and construct
      validity of the HIV-Related Fatigue Scale (HRFS), a 56-item self-report
      instrument developed through formative qualitative research and designed to
      measure the intensity and consequences of fatigue as well as the circumstances
      surrounding fatigue in people living with HIV. The HRFS has three main scales,
      which measure fatigue intensity, the responsiveness of fatigue to circumstances
      and fatigue-related impairment of functioning. The functioning scale can be
      further divided into subscales measuring impairment of activities of daily
      living, impairment of mental functioning and impairment of social functioning.
      Each scale demonstrated high internal consistency (Cronbach's alpha=0.93, 0.91
      and 0.97 for the intensity, responsiveness and functioning scales, respectively).
      The HRFS scales also demonstrated satisfactory convergent validity when compared
      to other fatigue measures. HIV-Related Fatigue Scales were moderately correlated
      with quality of nighttime sleep (rho=0.46, 0.47 and 0.35) but showed only weak
      correlations with daytime sleepiness (rho=0.20, 0.33 and 0.18). The scales were
      also moderately correlated with general mental and physical health as measured by
      the SF-36 Health Survey (rho ranged from 0.30 to 0.68 across the 8 SF-36
      subscales with most >0.40). The HRFS is a promising tool to help facilitate
      research on the prevalence, etiology and consequences of fatigue in people living
      with HIV.

PMID- 18608086
TI  - The epidemiology of HIV infection in Zambia.
AB  - Population surveys of health and fertility are an important source of information
      about demographic trends and their likely impact on the HIV/AIDS epidemic. In
      contrast to groups sampled at health facilities they can provide nationally and
      regionally representative estimates of a range of variables. Data on HIV-sero
      status were collected in the 2001 Zambia Demographic and Health Survey (ZDHS) and
      made available in a separate data file in which HIV status was linked to a very
      limited set of demographic variables. We utilized this data set to examine
      associations between HIV prevalence, gender, age and geographical location. We
      applied the generalized geo-additive semi-parametric model as an alternative to
      the common linear model, in the context of analyzing the prevalence of HIV
      infection. This model enabled us to account for spatial auto-correlation, non
      linear, location effects on the prevalence of HIV infection at the disaggregated
      provincial level (nine provinces) and assess temporal and geographical variation
      in the prevalence of HIV infection, while simultaneously controlling for
      important risk factors. Of the overall sample of 3950, 54% was female. The
      overall HIV-positivity rate was 565 (14.3%). The mean age at HIV diagnosis for
      male was 30.3 (SD=11.2) and 27.7 (SD=9.3) for female respectively. Lusaka and
      Copperbelt have the first and second highest prevalence of AIDS/HIV (marginal
      odds ratios of 3.24 and 2.88, respectively) but when the younger age of the urban
      population and the spatial auto-correlation was taken into account, Lusaka and
      Copperbelt were no longer among the areas with the highest prevalence. Non-linear
      effects of age at HIV diagnosis are also discussed and the importance of spatial
      residual effects and control of confounders on the prevalence of HIV infection.
      The study was conducted to assess the spatial pattern and the effect of
      confounding risk factors on AIDS/HIV prevalence and to develop a means of
      adjusting estimates of AIDS/HIV prevalence on the important risk factors.
      Controlling for important risk factors, such as geographical location (spatial
      auto-correlation), age structure of the population and gender, gave estimates of
      prevalence that are statistically robust. Researchers should be encouraged to use
      all available information in the data to account for important risk factors when
      reporting AIDS/HIV prevalence. Where this is not possible, correction factors
      should be applied, particularly where estimates of AIDS/HIV prevalence are pooled
      in systematic reviews. Our maps can be used for policy planning and management of
      AIDS/HIV in Zambia.

PMID- 18608087
TI  - The costs of amyotrophic lateral sclerosis, according to type of care.
AB  - Our objective was to estimate the economic burden of patients with amyotrophic
      lateral sclerosis (ALS) and to examine the effect of treatment in a
      multidisciplinary ALS treatment centre versus general care on costs and to
      describe differences in costs according to clinical characteristics. In a cross
      sectional study 208 patients with ALS and their caregivers were interviewed and
      were asked to fill in a cost diary for six months. Patients were divided in
      groups according to type of treatment they received and according to clinical
      characteristics (site of onset, severity). The direct healthcare and non
      healthcare costs were calculated according to Dutch guidelines for cost analysis
      in healthcare research, standardized for the year 2003. Ninety-eight patients
      were included when they had filled in the cost diary for at least three months
      and were affected for three years or less. Mean monthly costs were 1336 euros for
      the group receiving multidisciplinary care and 1271 euros for those receiving
      general care. This study shows that the costs of multidisciplinary ALS care were
      practically identical to the costs of general care. Earlier study showed that
      patients receiving multidisciplinary care had a better quality of life;
      therefore, the present study encourages the formation of multidisciplinary teams
      of professionals specialized in ALS care to further improve standards of care and
      QoL of patients suffering from ALS.

PMID- 18608088
TI  - Heterozygous S44L missense change of the spastin gene in amyotrophic lateral
      sclerosis.
AB  - The authors present a 50-year-old patient with adult-onset amyotrophic lateral
      sclerosis (ALS) that was rapidly progressing. Screening of the spastin gene
      revealed a heterozygous missense change S44L. We excluded the involvement of the
      ALS-linked gene for copper/zinc superoxide dismutase (SOD1). This unusual
      phenotype shows that allelic variants of spastin may predispose bearers to a
      greater spectrum of motor neuron disorders including ALS.

PMID- 18608089
TI  - Thrombopoietin is ineffective in a mouse model of motor neuron disease.
AB  - This study assessed the therapeutic efficacy of thrombopoietin (TPO) in the mouse
      model of ALS using two treatment paradigms. TPO was administered either daily or
      in 13-day treatment cycles to SOD1-G93A mice. Quantitative analysis of platelet
      levels, VEGF and TGF-beta1 trophic factors were assessed. The effect of TPO on
      disease progression was analyzed by behavioral analysis and clinical examination.
      TPO treatment increased levels of platelets and TGF-beta1 but not VEGF. This
      treatment did not affect onset or survival in these mice. Although biologically
      active, demonstrated by increased platelet and TGF-beta1 levels, rmTPO did not
      attenuate disease progression in ALS mice.

PMID- 18608090
TI  - A systematic review of antioxidant treatment for amyotrophic lateral 
      sclerosis/motor neuron disease.
AB  - Free radical accumulation and oxidative stress have been proposed as contributing
      to the progression of amyotrophic lateral sclerosis (motor neuron disease). A
      range of antioxidant medications is available, and has been studied. We aimed to
      examine the effects of antioxidant medication in the treatment of people with
      amyotrophic lateral sclerosis, and searched the Cochrane Neuromuscular Disease
      Group Trials register (August 2005), MEDLINE (January 1966 to August 2005),
      EMBASE (January 1980 to August 2005) and other sources. Selection criteria were
      all randomized or quasi-randomized controlled trials of antioxidant treatment for
      amyotrophic lateral sclerosis. The authors independently applied the selection
      criteria, assessed study quality and two authors performed independent data
      extraction. The search identified 23 studies for consideration but only nine
      studies met the inclusion criteria. Only two studies used our predetermined
      primary outcome measure as the primary outcome measure (survival at 12 months
      treatment). However, sufficient data were available from four studies to allow
      analysis of this outcome measure, and a meta-analysis was performed. In the
      individual studies no significant effect was observed for vitamin E 500 mg twice
      daily; vitamin E 1 g five times daily; acetylcysteine 50 mg/kg daily subcutaneous
      infusion; or a combination of L-methionine 2 g, vitamin E 400 International
      Units, and selenium 0.03 mg three times daily (Alsemet). No significant effect on
      the primary outcome measure was observed in a meta analysis of all antioxidants
      combined. No significant differences were demonstrated in any of the secondary
      outcome measures. In the opinion of the reviewers, there is insufficient evidence
      of efficacy of individual antioxidants, or antioxidants in general, in the
      treatment of people with amyotrophic lateral sclerosis. One study reported a mild
      positive effect, but this was not supported by the analysis we used. Generally,
      the studies were poorly designed, and underpowered, with low numbers of
      participants and of short duration. Further well-designed trials of medications
      such as vitamin C and E are unlikely to be performed. If future trials of
      antioxidant medications are performed, careful attention should be given to
      sample size, outcome measures, and duration of the trial. The high tolerance and
      safety, and relatively low cost of vitamins C and E, and other considerations
      related to the lack of other effective treatments for amyotrophic lateral
      sclerosis, explain the continuing use of these vitamins by physicians and people
      with amyotrophic lateral sclerosis. While there is no substantial clinical trial
      evidence to support their clinical use, there is no clear contraindication.

PMID- 18608091
TI  - 50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1
      expression in vitro and may correlate with increased age of onset of sporadic
      amyotrophic lateral sclerosis.
AB  - The objective was to test the hypothesis that a described association between
      homozygosity for a 50bp deletion in the SOD1 promoter 1684bp upstream of the SOD1
      ATG and an increased age of onset in SALS can be replicated in additional SALS
      and control sample sets from other populations. Our second objective was to
      examine whether this deletion attenuates expression of the SOD1 gene. Genomic DNA
      from more than 1200 SALS cases from Ireland, Scotland, Quebec and the USA was
      genotyped for the 50bp SOD1 promoter deletion. Reporter gene expression analysis,
      electrophoretic mobility shift assays and chromatin immunoprecipitation studies
      were utilized to examine the functional effects of the deletion. The genetic
      association for homozygosity for the promoter deletion with an increased age of
      symptom onset was confirmed overall in this further study (p=0.032), although it
      was only statistically significant in the Irish subset, and remained highly
      significant in the combined set of all cohorts (p=0.001). Functional studies
      demonstrated that this polymorphism reduces the activity of the SOD1 promoter by
      approximately 50%. In addition we revealed that the transcription factor SP1
      binds within the 50bp deletion region in vitro and in vivo. Our findings suggest
      the hypothesis that this deletion reduces expression of the SOD1 gene and that
      levels of the SOD1 protein may modify the phenotype of SALS within selected
      populations.

PMID- 18608092
TI  - Scrutinizing enrollment in ALS clinical trials: room for improvement?
AB  - Enrollment in ALS trials has not been systematically studied. We surveyed the ALS
      Research Group (ALSRG) to learn their impressions of enrollment at ALS clinics
      across North America. We also reviewed completed ALS trials to determine an
      enrollment rate (subjects per site per month), its variability across trials,
      whether it is changing over time, and whether it is influenced by 'trial
      factors'. ALSRG members were polled via an online survey. ALS trials were
      identified by literature review and investigator contact. Enrollment rate versus
      publication year was plotted for each trial. Models were created to examine how
      'trial factors' were associated with enrollment rate. By survey, percent
      enrollment is 25% and highly variable (range 0-75%). By literature review,
      enrollment rate is 2.2 participants/site/month and highly variable (range 0.1
      7.5). Enrollment is not improving over time; no 'trial factor' explains the
      variability in enrollment across trials. Behaviors among clinic directors and
      patients were identified that may influence enrollment. In conclusion, ALS trial
      enrollment rate is low, highly variable and not influenced by trial design
      factors. 'Patient factors' and 'physician factors' may play more important roles
      in influencing enrollment, as in oncology trials. Our survey data support this
      idea, and provide potential mechanisms for improving enrollment.

PMID- 18608094
TI  - Aggregation of neurodegenerative disease in ALS kindreds.
AB  - The objective was to investigate the familial occurrence of the neurodegenerative
      condition amyotrophic lateral sclerosis (ALS), Parkinson's disease and dementia
      in the relatives of Irish ALS patients. A retrospective case control chart review
      study was conducted to extract the neurological family histories of Irish ALS
      patients and controls who attended the National Neurological Centre between
      January 2001 and January 2006. In total, details were extracted from 197 ALS and
      235 general neurology pedigrees. Using the recurrence risk, lambda, ALS (lambda
      (1st degree)=7.77), Parkinson's disease (lambda (1st degree)=2.67) and dementia
      (lambda (1st degree)=6.21) were reported more frequently in relatives of ALS
      patients compared to those of non-ALS controls. Within sporadic ALS kindreds, the
      presence of neurodegenerative disease was not uniformly distributed. This study
      supports the conjecture that neurodegenerative disease aggregates within ALS
      kindreds, and indicates a shared genetic susceptibility towards some
      neurodegenerative phenotypes.

PMID- 18608095
TI  - Clinical phenotypes and natural progression for motor neuron disease: analysis
      from an Australian database.
AB  - From 1997 to 2003 we prospectively followed a cohort of ALS/MND patients.
      Patients were allocated to predetermined clinical phenotypes using the principles
      established in the modified El Escorial criteria. The date and region of symptom
      onset were carefully determined and their progression was scored using the Appel
      ALS rating scale. The four distinct clinical phenotypes: Global, Flail Arm, Flail
      Leg and Primary Lateral Sclerosis (PLS) demonstrated significantly different
      rates of progression and survival times. The Global ALS/MND phenotype can present
      with initial symptoms in any region and rapidly progresses to involve all
      segments, with symptoms due to a mixture of combined corticospinal tract and
      anterior horn cell dysfunction. The Global phenotype has the shortest survival
      and most rapid rate of disease progression. There was a significant difference in
      survival between Global bulbar onset and cervical onset disease but no
      significant difference in the rate of disease progression between the three
      Global subgroups as determined by the Appel/ALS rating scale. Flail patients had
      much slower rates of progression and significantly longer survival compared to
      the Global phenotype. Patients with Primary Lateral Sclerosis as expected
      progressed the slowest and survived the longest compared to the other clinical
      phenotypes. The utility of developing a method of assigning clinical phenotypes
      with similar survival and disease progression rates is discussed in relation to
      therapeutic trial design, practice benchmarking and clinico-pathological
      correlations.

PMID- 18608096
TI  - Muscle histopathology in upper motor neuron-dominant amyotrophic lateral
      sclerosis.
AB  - The distinction between primary lateral sclerosis (PLS) and amyotrophic lateral
      sclerosis (ALS) still remains debated. Recently, PLS patients displaying lower
      motor neuron (LMN) signs have been defined as 'upper motor neuron (UMN)-dominant
      ALS', using 'clinically pure PLS' diagnosis to those with no LMN signs. To
      further characterize the LMN involvement in UMN-dominant ALS we investigated the
      presence and the extent of neurogenic abnormalities in the skeletal muscle of
      patients affected with a pyramidal syndrome consistent with UMN-dominant ALS. A
      total of nine patients affected with UMN-dominant ALS were analysed. In all
      cases, muscle biopsies showed the presence of scattered or clustered atrophic
      angulated fibres in small groups, and a mild to moderate fibre type-grouping.
      Target and targetoid fibres were detected in two cases only. Three patients had a
      second muscle biopsy which demonstrated a roughly unchanged pattern of chronic
      denervation with still moderate reinnervation phenomena. This study suggests that
      in UMN-dominant ALS muscle denervation may be characterized by an early chronic
      impairment of a restricted number of LMNs. The extent rather than the presence of
      LMN signs may allow to categorize patients with motor neuron disease involving
      mainly UMN into distinct entities.

PMID- 18608093
TI  - A novel, efficient, randomized selection trial comparing combinations of drug
      therapy for ALS.
AB  - Combining agents with different mechanisms of action may be necessary for
      meaningful results in treating ALS. The combinations of minocycline-creatine and
      celecoxib-creatine have additive effects in the murine model. New trial designs
      are needed to efficiently screen the growing number of potential neuroprotective
      agents. Our objective was to assess two drug combinations in ALS using a novel
      phase II trial design. We conducted a randomized, double-blind selection trial in
      sequential pools of 60 patients. Participants received minocycline (100 mg)
      creatine (10 g) twice daily or celecoxib (400 mg)-creatine (10 g) twice daily for
      six months. The primary objective was treatment selection based on which
      combination best slowed deterioration in the ALS Functional Rating Scale-Revised
      (ALSFRS-R); the trial could be stopped after one pool if the difference between
      the two arms was adequately large. At trial conclusion, each arm was compared to
      a historical control group in a futility analysis. Safety measures were also
      examined. After the first patient pool, the mean six-month decline in ALSFRS-R
      was 5.27 (SD=5.54) in the celecoxib-creatine group and 6.47 (SD=9.14) in the
      minocycline-creatine group. The corresponding decline was 5.82 (SD=6.77) in the
      historical controls. The difference between the two sample means exceeded the
      stopping criterion. The null hypothesis of superiority was not rejected in the
      futility analysis. Skin rash occurred more frequently in the celecoxib-creatine
      group. In conclusion, the celecoxib-creatine combination was selected as
      preferable to the minocycline-creatine combination for further evaluation. This
      phase II design was efficient, leading to treatment selection after just 60
      patients, and can be used in other phase II trials to assess different agents.

PMID- 18608097
TI  - Implications of blood-brain barrier disruption in ALS.
AB  - Our letter to the editor addresses important questions regarding the role of the
      blood-spinal cord barrier in amyotrophic lateral sclerosis. The novel finding of
      barrier dysfunction in ALS has implications for disease pathogenesis. This
      discussion should prove of widespread interest to researchers and may help in
      formulating various new therapeutic strategies to protect barrier function and
      thus extend functionality and lifespan in ALS patients.

PMID- 18608098
TI  - Medications and laboratory parameters as prognostic factors in amyotrophic
      lateral sclerosis.
AB  - We sought to examine the influence of medication usage and laboratory
      measurements on disease progression in amyotrophic lateral sclerosis (ALS). A
      database of 596 volunteers with ALS was generated from three clinical trials and
      one observational study. Disease course was measured by survival and three
      functional measures: the ALS Functional Rating Scale (ALSFRS), Vital Capacity
      (VC) and Maximum Voluntary Isometric Contraction (MVIC). Survival modeling was
      performed using Cox proportional hazards regression. The association of
      medication or laboratory measurements with disease progression was determined
      using a random effects model. In the multivariate analysis, survival was shorter
      in participants who took aspirin (HR =1.93, p =0.046); NSAIDs (HR =1.51, p
      =0.054); had low blood chloride (HR =0.76, p =0.020) or high bicarbonate levels
      (HR =1.37, p =0.006). Individuals who took calcium had better survival (HR =0.37,
      p =0.008) and a slower rate of decline of MVIC arm megascore (p =0.033). Vital
      capacity declined faster in individuals with lower serum chloride (p<0.0001), or
      higher bicarbonate (p =0.002) levels and those taking paracetamol (acetaminophen)
      (p =0.035). We conclude that aspirin or NSAID use may shorten survival in ALS,
      while calcium use may prolong survival. Our results support a need to further
      explore the role of neuroinflammation in the pathogenesis of ALS.

PMID- 18608099
TI  - ALSOD: the Amyotrophic Lateral Sclerosis Online Database.
AB  - More than 100 point mutations spanning the 153 amino acid SOD1 sequence have been
      identified in individuals with ALS. In 1999 the Amyotrophic Lateral Sclerosis
      Database (ALSOD) was generated to store these mutations along with ALS patient
      information to facilitate the identification of a correlation between the SOD1
      genotype with the ALS phenotype. Here we report our ongoing development and
      redesign of the ALSOD database and its automated procedures. The significant new
      features have improved ALSOD, helping link the mutations of the SOD1 gene to the
      hypothetical three-dimensional protein structural rearrangement, and the
      resulting ALS phenotype. Additionally, ALSOD now provides a more comprehensive
      knowledge base for ALS, detailing genetic, proteomic, and bioinformatics
      information associated with the disease. ALSOD can be accessed at
      http://alsod.iop.kcl.ac.uk/als/.

PMID- 18608101
TI  - Screening of hypoxia-inducible genes in sporadic ALS.
AB  - Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have
      been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations
      in these genes may reduce the levels or functioning of their products. VEGF and
      ANG belong to a larger group of angiogenic genes that are up-regulated under
      hypoxic conditions. We hypothesized that common genetic variation across other
      members of this group may also predispose to sporadic ALS. To screen other
      hypoxia-inducible angiogenic genes for association with SALS, we selected 112
      tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic
      variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes.
      Screening for association was performed in 270 Irish individuals with typical
      SALS and 272 ethnically matched unrelated controls. SNPs showing association in
      the Irish phase were genotyped in a replication sample of 281 Swedish sporadic
      ALS patients and 286 Swedish controls. Seven markers showed association in the
      Irish. The one modest replication signal observed in the Swedish replication
      sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs.
      the Irish cohort. We failed to detect association of common variation across 24
      candidate hypoxia-inducible angiogenic genes with SALS.

PMID- 18608100
TI  - Insulin-like growth factor-I for the treatment of amyotrophic  lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      that affects both upper and lower motorneurons (MN) resulting in weakness,
      paralysis and subsequent death. Insulin-like growth factor-I (IGF-I) is a potent
      neurotrophic factor that has neuroprotective properties in the central and
      peripheral nervous systems. Due to the efficacy of IGF-I in the treatment of
      other diseases and its ability to promote neuronal survival, IGF-I is being
      extensively studied in ALS therapeutic trials. This review covers in vitro and in
      vivo studies examining the efficacy of IGF-I in ALS model systems and also
      addresses the mechanisms by which IGF-I asserts its effects in these models, the
      status of the IGF-I system in ALS patients, results of clinical trials, and the
      need for the development of better delivery mechanisms to maximize IGF-I
      efficacy. The knowledge obtained from these studies suggests that IGF-I has the
      potential to be a safe and efficacious therapy for ALS.

PMID- 18608102
TI  - ALS: Family caregiver needs and quality of life.
AB  - The goal of this study was to determine the needs of ALS family caregivers.
      Utilizing a qualitative and quantitative mixed methodology known as Concept
      Mapping (CM), individual interviews with family caregivers of ALS patients (n
      =19) identified 109 needs. The needs were sorted and rated by 12 of the family
      caregivers, then analyzed using multidimensional scaling and cluster analysis. In
      addition, the caregivers completed the SF-8 QoL measure. The analysis resulted in
      a four-cluster map, representing the trajectory of the ALS family caregivers'
      needs: Stage 1: Early Coping and Adjustment; Stage 2: Maintenance; Stage 3:
      Transition to End Stage; and Stage 4: Coping with Change and Loss. The SF-8
      results indicated that caregivers who resided with their ALS family member have
      poorer mental and physical health than family caregivers who did not have primary
      residence with the ALS patient. In conclusion, a model of needs for ALS family
      caregivers was established. Future studies addressing these needs may improve QoL
      of ALS family caregivers as well as ALS patients.

PMID- 18608103
TI  - Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and
      ALSFRS.
AB  - Our objective was to determine the effect of creatine monohydrate on disease
      progression in patients with amyotrophic lateral sclerosis (ALS). One hundred and
      seven patients with the diagnosis of probable or definite ALS, of less than five
      years duration from symptom onset, were randomized to either treatment with daily
      creatine monohydrate (5 g/d) or placebo. In this multicenter, double-blinded
      study we followed changes in disease progression: using quantitative measures of
      strength via maximal isometric voluntary contraction, forced vital capacity,
      ALSFRS, quality of life, fatigue and survival. Patients were followed for nine
      months. The results showed that creatine monohydrate did not significantly
      improve motor, respiratory or functional capacity in this patient population. The
      drug was well tolerated and the study groups well balanced, especially
      considering the absence of forced vital capacity criteria for entrance into the
      study. There was a trend toward improved survival in patients taking daily
      creatine monohydrate and this was identical to the trend seen in another recently
      published report of creatine in ALS patients 1. In conclusion, creatine
      monohydrate (5 g/d) did not have an obvious benefit on the multiple markers of
      disease progression measured over nine months. We measured fatigue during
      isometric contraction and found no significant improvement despite anecdotal
      patient reports prior to and during the study. The trend toward improved survival
      was also found in another recently completed blinded trial using creatine
      monohydrate. Further investigation on the possible survival benefit of creatine
      in this patient population is ongoing.

PMID- 18608105
TI  - Are statin medications safe in patients with ALS?
AB  - Statin medications for elevated cholesterol are one of the most commonly
      prescribed medications worldwide. The aim of this study was to determine if
      statin medications affect the rate of disease progression, the severity and
      frequency of muscle cramping, and serum CK levels in patients with ALS. We
      conducted a prospective cohort study in patients diagnosed with ALS with statin
      medication as the predetermined exposure variable and the rate of decline of the
      ALS Functional Rating Scale-Revised (ALSFRS-R) as the primary outcome. One
      hundred and sixty-four consecutive patients with laboratory supported probable,
      clinically probable, or clinically definite ALS were evaluated from January 2006
      to September 2007. Thirty-two patients (20%) were taking statin medications and
      132 were in the control group. After adjusting for covariates, we found a highly
      significant increase in the rate of decline in the ALSFRS-R for the statin group
      (1.71 units/month) compared to the control group (1.05 units/month, pB0.0001)
      representing a 63% increase in the rate of functional decline. Patients on statin
      therapy also reported a significant increase in muscle cramp frequency and
      severity (pB0.0001). This study has demonstrated a strong association between
      statin medications and an increased rate of functional decline and muscle
      cramping in patients with ALS. Although this association does not prove a causal
      relationship, it is prudent to exercise caution and discuss discontinuation or
      replacement of statin medications in patients with ALS.

PMID- 18608104
TI  - The expression of metallothioneins is diminished in the spinal cords of patients
      with sporadic ALS.
AB  - We analyzed the expression of MTs using immunohistochemistry on the spinal cords
      of patients with ALS (n =12) and controls (n =12). The immunoreactivities of both
      MT-1/2 and MT-3 stained dominantly in glial cells and were decreased in the
      spinal cords of patients with ALS, particularly in patients on respirators. The
      immunoreactivity of MT-1/2 in the ALS groups was significantly reduced compared
      with controls. In addition, a statistical analysis revealed that the
      immunoreactivity of MT-3 in astrocytes in the gray matter of the lumbar spinal
      cord was negatively correlated with the duration of ALS. Both MT-1/2 and MT-3
      immunoreactivities were detected mainly in the glias and also detected in some
      neurons in both control patients and patients with ALS. Interestingly, the
      patients with MT-3-positive neurons showed definite MT-3-immunoreactive glial
      reaction around neurons. Previous studies have reported that familial ALS (FALS)
      model mice (G93A SOD1) crossed with MT-1/2 or MT-3 knock-out mice had accelerated
      expression of ALS. Judged from these findings, both MT-1/2 and MT-3 play
      important roles in the progression of ALS. MTs are defensive proteins that can
      scavenge free radicals; therefore, manipulation of their expression has a strong
      therapeutic potential for ALS patients.

PMID- 18608106
TI  - Further evidence that D90A-SOD1 mutation is recessively inherited in ALS patients
      in Italy.
AB  - Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have been reported to
      cause adult-onset autosomal dominant amyotrophic lateral sclerosis (FALS). In
      sporadic cases (SALS), de novo mutations in the SOD1 gene have occasionally been
      observed. All the SOD1 mutations are autosomal dominantly inherited with the
      exception of D90A. To date, in Italy, only two sporadic ALS cases carrying the
      D90A mutation have been reported in a homozygous state. We investigated for the
      presence of this mutation in 169 unrelated ALS patients from southern Italy. The
      genetic analysis revealed three ALS patients (1.8%) with mild phenotype carrying
      the homozygous D90A mutation.

PMID- 18608107
TI  - Whole brain-based computerized neuroimaging in ALS and other motor neuron
      disorders.
AB  - Advanced neuroimaging applications to patients suffering from ALS and other motor
      neuron disorders (MND) have a high potential in terms of understanding the
      pathophysiology and visualizing the in vivo pathoanatomy of the diseases. In this
      context, particularly observer-independent computerized analyses of magnetic
      resonance imaging (MRI) data are of special interest since they overcome
      shortcomings of region-of-interest-based techniques. For three-dimensional
      structural T1-weighted MRI of the whole brain, voxel-based morphometry (VBM) has
      proven the most valuable approach to analyse regional volume alterations of the
      grey or white matter at group level. For the analysis of the white matter
      integrity with respect to tissue diffusivity and white matter connectivity
      including fibre tracking algorithms, diffusion tensor imaging (DTI) which can
      also be performed on a whole brain-basis is of the highest potential to date.
      Both VBM and DTI have been applied to various MND, in particular ALS, in multiple
      studies over recent years and have substantially broadened our knowledge about
      their in vivo pathoanatomy and mechanisms of neurodegeneration. Especially both
      the degree of damage to motor areas and the involvement of non-motor areas are of
      interest to be subjected to quantitative assessment, in order to establish
      quantitative surrogate markers for disease progression usable in clinical trials.
      Here, the technical state-of-the-art and the results of VBM and DTI studies in
      MND as the current state are reviewed, and future perspectives for further
      neuroimaging applications are highlighted.

PMID- 18608108
TI  - Proteomic analysis of plasma from Portuguese patients with familial amyotrophic
      lateral sclerosis.
AB  - In ALS, the identification of abnormal proteins in biological fluids might be
      useful for the understanding of the ethiopathogenesis of the disease.
      Furthermore, it can provide biomarkers useful for diagnosis, to monitor disease
      progression and to study the effect of drugs. Plasma is a suitable fluid for
      screening such targets since blood collection is a relatively simple procedure.
      In this study, proteomic techniques consisting of two-dimensional gel
      electrophoresis and matrix-assisted laser desorption time-of-flight mass
      spectrometry (MALDI-TOF MS) have been used for the analysis of plasma from a
      group of Portuguese familial ALS (FALS) patients not carrying SOD1 mutations, age
      matched healthy controls, sporadic ALS patients and controls with other muscular
      disorders. Most relevant was the finding in the FALS patients of an isoform of
      vitamin D-binding protein (DBP) at pI 5.2, identified as GC2 by liquid
      chromatography electrospray ionization-TOF MS. GC2 was absent from the healthy
      controls. Concomitantly, decrease of more acidic isoforms of DBP was observed for
      the FALS patients. The results suggested that the GC2 polymorphism of DBP could
      constitute a risk factor for ALS.

PMID- 18608109
TI  - Maternal fish consumption in the nutrition transition of the Amazon Basin: growth
      of exclusively breastfed infants during the first 5 years.
AB  - BACKGROUND: Changes in fish-eating habits due to rapid urbanization in Western
      Amazon was used as model to investigate whether maternal fish-intake rate impacts
      on children's weight and height during the first 5 years. AIM: The study examined
      the growth of 82 breastfed children, and maternal fish consumption (hair mercury
      concentrations, HHg) during pregnancy and lactation. SUBJECTS AND METHODS: Fish
      consumption in mothers and children was estimated through HHg. The children were
      measured and weighed at birth and at 6 (exclusive breastfeeding), 36 and 60
      months. RESULTS: Fish consumption rate (HHg) had no significant impact on
      children's growth at the specified ages (p = 0.35). After 6 months of exclusive
      breastfeeding, children had the highest proportion of Z-scores <-1 SD; however,
      weaning (with extended breastfeeding) had a substantial impact in moving up the
      attained growth at 3 years. The duration of breastfeeding was significantly
      correlated with attained Z-scores for weight-for-age (r = 0.26; p = 0.02) and
      weight-for-height (r = 0.22; p = 0.04) but not for height-for-age. At 3 years
      most children had improved Z-scores (>-1 SD) for height-for-age (70/82), weight
      for-age (74/82) and weight-for-height (74/82). At 5 years, all but one child
      attained Z-scores >-1. CONCLUSION: The apparently good nutritional status of
      subjects is more likely due to a well balanced diet composition than to only one
      dietary protein source--fish.

PMID- 18608110
TI  - Lower calcaneal bone mineral density and broadband ultrasonic attenuation, but
      not speed of sound, in South Asian than white European women.
AB  - BACKGROUND: Quantitative ultrasound (QUS) measures of bone predict fracture risk
      in older white women. South Asian women have low bone mineral density (BMD),
      perhaps related to smaller body size or vitamin D insufficiency, but it is
      unknown whether this is accompanied by lower QUS. AIM: The study compared QUS,
      BMD and vitamin D status between South Asian and white European women. SUBJECTS
      AND METHODS: Participants were 47 postmenopausal women (23 white European, 24
      South Asian) aged 55-65 years. BMD was measured at the calcaneus and radius by
      dual X-ray absorptiometry. The QUS measurements were broadband ultrasound
      attenuation (BUA) at the calcaneus and speed of sound (SOS) at the calcaneus,
      radius and tibia. Serum 25-hydroxy vitamin D was determined in late summer.
      RESULTS: South Asian women had significantly lower serum 25-hydroxyvitamin D than
      white Europeans (13.0 +/- 5.1 versus 30.3 +/- 7.1 ng mL(-1); p < 0.001).
      Calcaneal BMD and BUA were 14% and 10% lower (p = 0.016 and 0.045), respectively,
      in South Asian women. Radial BMD, and SOS at all sites, did not differ
      significantly between groups. CONCLUSION: In this study, postmenopausal South
      Asian women living in the UK had a high prevalence of vitamin D insufficiency and
      lower calcaneal BMD than white European women, consistent with previous findings.
      Differences were detected in calcaneal BUA but not SOS. Further research is
      needed to evaluate fracture risk and its detection in South Asian women.

PMID- 18608111
TI  - Validation of a 7-day physical activity diary against doubly-labelled water.
AB  - BACKGROUND: The assessment of physical activity intensity and duration is
      essential for understanding group activity patterns. METHODS: The present study
      evaluated the validity of measurement of total energy expenditure (TEE) and
      physical activity level (PAL) using a categorized physical activity diary. In 29
      young healthy men, aged 18-27 years, with body mass index range 21-43 kg m(-2),
      TEE using doubly-labelled water (DLW), resting metabolic rate (RMR) by indirect
      calorimetry, physical activity level (PAL defined as TEE/RMR) and activity
      pattern, timing and level from 7-day physical activity diaries were determined.
      RESULTS: TEE by DLW and estimated by activity diary were correlated (r = 0.61, p
      = 0.005). The mean underestimation of TEE by the activity diary compared with the
      DLW method was 2.50 +/- 0.72 MJ day(-1). Sedentary (lying, sitting and standing)
      time averaged 18 h day(-1) and was negatively correlated with PAL (r = -0.44, p =
      0.018) whilst time spent in light intensity activity (5 h day(-1)) was positively
      correlated (r = 0.51, p = 0.005). CONCLUSIONS: It is concluded that the
      categorized physical activity diary measured TEE with limited accuracy but
      presents an inexpensive, convenient method of discriminating individual and group
      physical activity patterns.

PMID- 18608112
TI  - A cross-sectional examination of growth indicators from Thai adolescent girls:
      evidence of obesity among Thai youth?
AB  - BACKGROUND: Few studies have examined growth data from adolescent girls in
      Southeast Asia and almost none have been carried out in Thailand. Thus this study
      examines growth data from Thai adolescent girls. AIM: Cross-sectional growth data
      from a sample of Thai girls were compared to reference data from healthy well
      nourished girls. It is hypothesized that the reference girls will be taller and
      heavier than the Thai girls; however, the growth indicators will also indicate
      that obesity is present among Thai girls. SUBJECTS AND METHODS: Anthropometric
      and age at menarche data were collected from a sample of 319 adolescent girls
      ages 11-17 years living in suburban Thailand. RESULTS: Thai girls are heavier
      than the reference girls at ages 11-13 years yet are shorter and lighter than the
      reference girls at ages 14-17 years. The data also reveal that 18.4% of the girls
      are overweight or obese as classified by the CDC BMI-for-age percentile growth
      curves. CONCLUSION: The findings suggest the presence of overweight and obesity
      among this adolescent Thai population. These data may reflect the impact of the
      improved economic situation of Thailand as well as the impact of body image
      concerns among these young girls.

PMID- 18608113
TI  - Duffy blood group system genotyping in an urban Tunisian population.
AB  - BACKGROUND: The Duffy blood group system, besides its relevance in transfusion
      medicine, is of major interest for population genetics. In fact, the Duffy
      molecule is the only red cell receptor for Plasmodium vivax, thus the fixation of
      FY*silent allele in western south-Saharan Africa resulted in the absence of this
      type of malaria in that area (for a review see Kwiatowski, Am J Hum Genet 77:171
      192, 2005). For the Duffy functional role see, for example, Daniels (Vox
      Sanguinis 93:331-340, 2007). METHODS: Duffy blood group distribution in 115
      unrelated Tunisians was determined using the polymerase chain reaction with
      sequence specific primer (PCR-SSP) method detecting the five allelic versions of
      the FY gene. The red cell antigenic FY phenotype, for each donor, was deduced
      through DNA analysis. The blood samples of the positive FY*X alleles were
      investigated by serological methods, mainly the fixation-elution technique.
      RESULTS: The following allele frequencies were found (after having excluded FY*X,
      which had frequency of 0.0174): FY*1 = 0.291 (expressed 0.260; silent 0.031);
      FY*2 = 0.709 (expressed 0.427; silent 0.282). The most surprising result in this
      work is the detection of the FY*1 silent allele, usually quite rare, in four
      samples (1.74%). For FY*2 silent, the predominant allele in Africans, genotyping
      results showed a prevalence of 29.57%. The FY locus was in Hardy-Weinberg
      equilibrium in the present sample. CONCLUSION: When compared with European and
      African data, Tunisian samples demonstrated the presence of the common signs of
      these two ancestries (FY*2 and FY*X for the first population; and FY*2 silent for
      the last one). These data confirm the mixed roots of this urban Tunisian
      population already suggested by numerous studies on other haematological markers.

PMID- 18608114
TI  - Strengthening causal inference in cardiovascular epidemiology through Mendelian
      randomization.
AB  - Observational studies have contributed in a major way to understanding modifiable
      determinants of cardiovascular disease risk, but several examples exist of
      factors that were identified in observational studies as potentially protecting
      against coronary heart disease, that in randomized controlled trials had no such
      effect. The likely reason for misleading findings from observational
      epidemiological studies is that associations are influenced by confounding, bias,
      and reverse causation--where disease influences a risk factor, rather than vice
      versa. Mendelian randomization utilizes genetic variants that serve as proxy
      measures for modifiable risk factors to allow estimation of the causal influence
      of the modifiable risk factor in question. We present examples of the use of the
      Mendelian randomization approach and discuss both the limitations and potentials
      of this strategy.

PMID- 18608116
TI  - Coronary angioplasty in drug eluting stent era for the treatment of unprotected
      left main stenosis compared to coronary artery bypass grafting.
AB  - BACKGROUND: Improved outcomes of percutaneous coronary interventions (PCI) with
      drug-eluting stents (DES) have resulted in their expanded use for left main
      coronary artery (LMCA) stenosis. AIM: We compared outcomes of patients undergoing
      PCI for unprotected LMCA stenosis and patients treated by coronary artery bypass
      grafting (CABG). METHOD: Between January 2005 and January 2007, 6705 patients
      were studied with coronary angiography in northern Finland. All subjects treated
      with revascularization of LMCA stenosis (n = 287) were included and followed up
      for a mean of 12+6 months. RESULTS: From 287 patients, 238 underwent CABG, and 49
      had PCI with DES. The incidence of 1-year mortality was 4% among the PCI-treated
      and 11% among CABG-treated patients (P = 0.136). After the first month, mortality
      among PCI-or CABG-treated patients did not differ statistically significantly (2%
      versus 7%, P = 0.133). The most significant independent predictor of mortality
      was reduced left ventricular systolic function (hazard ratio 14.9, 95% CI 5.5
      40.0, P < 0.001). CONCLUSIONS: PCI with DES for selected LMCA disease patients
      results in short- and midterm outcomes comparable to results of CABG in general.
      PCI is a viable therapeutic option in selected patients with LMCA stenosis.

PMID- 18608117
TI  - Help me, Doctor! My D-dimer is raised.
AB  - Although optimal strategy for management of patients with suspected venous
      thromboembolism depends on local expertise and cost, diagnostic algorithms
      including clinical assessment and D-dimer have been validated in several trials.
      However, a new paradigm shift is emerging, giving an extended role of D-dimer
      measurement in clinical practice. D-dimer is a useful biomarker to help determine
      initial anticoagulant therapy in patients with thrombosis. Emerging evidence also
      endorses a 'predictive' role for raised D-dimer levels, since its measurement
      provides prognostic indications for a variety of conditions, including venous
      thromboembolism, disseminated intravascular coagulation, cardiovascular disease,
      infectious diseases, and cancer. Additional investigation is needed to clarify
      whether raised D-dimer is an epiphenomenon or it is actively involved in
      pathophysiology. Further studies are also required to establish whether D-dimer
      testing, alone or combined with other prognostic indicators, can be used to
      identify patient candidates for further triage and treatment. Nevertheless, the
      hazard(s) associated with raised D-dimer in plasma requires re-emphasis in the
      teaching of post-graduates, junior doctors and medical students, including the
      most effective treatments to inhibit clot spread and decrease the probability of
      further significant thrombotic incidents even in the absence of any 'detectable'
      thrombosis.

PMID- 18608118
TI  - The genetic and environmental basis of atopic diseases.
AB  - The prevalence of atopic diseases has increased abruptly in recent years in most
      Westernized societies, making the question why this happened the topic of a
      heated debate. The best paradigm available to date to explain this steep rise,
      the 'hygiene hypothesis', supports that it is the excess 'cleanliness' of our
      environments that has led to the decline in the number of infectious stimuli that
      are necessary for the proper development of our immune system. Recent findings
      support that it is the combined effect that not only pathogenic, but also non
      pathogenic microorganisms, and even their structural components,can exert on the
      immune system that deters from the development of atopic responses. Adding to
      these results are intriguing new findings on the effect different gene
      polymorphisms can have on an individual's predisposition to allergic diseases.
      The most important linkages produced, to date, include those among the genes for
      IL-4, IL-13, HLA-DRB, TNF, LTA,FCER1B, IL-4RA, ADAM33, TCR alpha/delta, PHF11,
      GPRA, TIM, p40, CD14, DPP10, T-bet, GATA-3, and FOXP3 and allergic disorders. The
      two parallel research efforts, epidemiologic and genetic, are only recently
      starting to converge,producing fascinating results on the effect particular gene
      environment interactions might have in the development of atopy.The most
      important lesson learned through this tremendous research effort is that not only
      a small number but thousands and millions of separate risk factors act in
      concordance in the production of the allergic phenotype.

PMID- 18608119
TI  - Smoking and low serum testosterone associates with high concentration of oxidized
      LDL.
AB  - BACKGROUND: The interplay between smoking, oxidized low-density lipoprotein
      cholesterol (ox-LDL) and gonadal hormones has been scarcely investigated. AIM: To
      investigate associations in ox-LDL and gonadal hormones in smokers and non
      smokers METHODS: Participants (n=164) were obtained from a population cohort of
      Finnish men aged 40-70 years. The subjects answered a detailed questionnaire on
      their health behaviour, medication, diseases, and different symptoms, and the
      hormonal and lipid profiles were measured. RESULTS: Smokers (n=33) had higher
      levels of ox-LDL (21%) and more free testosterone (12%) (P<0.01 for all) than non
      smokers (n=131). The difference between smokers and non-smokers in ox-LDL
      persisted after controlling for possible confounding factors. When the smokers
      were divided into two subgroups (n=16 and n=17) according to total testosterone
      (< or =15 and >15 nmol/L), the ox-LDL in the low-testosterone subgroup was
      significantly higher (30%) than in the high-testosterone group (P=0.006).
      Similarly in the corresponding non-smoking subgroups (n=72 and n=59), ox-LDL was
      significantly higher (11%) in the low-testosterone subgroup than in the high
      testosterone subgroup (P=0.012). CONCLUSIONS: Smoking men have significantly more
      ox-LDL than non-smoking men. Furthermore, if smoking is combined with a low serum
      testosterone, ox-LDL is even higher. This may suggest a higher risk for
      atherosclerosis.

PMID- 18608120
TI  - Cancer, stem cells, and oncolytic viruses.
AB  - Cells with stem cell-like attributes, such as self-renewal and pluripotency, have
      been isolated from hematological malignancies and from several solid tumor types.
      Tumor-initiating cells, also referred to as cancer stem cells, are thought to be
      responsible for the initiation and growth of tumors. Like their normal
      counterparts, putative cancer stem cells show remarkable resistance to radiation
      and chemotherapy. Their capacity for surviving apparently curative treatment can
      result in tumor relapse. Novel approaches that target tumor-initiating cells in
      addition to differentiated malignant cells, which constitute the bulk of the
      tumor, are required for improved survival of patients with metastatic tumors.
      Oncolytic viruses enter cells through infection and may therefore be resistant to
      defense mechanisms exhibited by cancer stem cells. Oncolytic adenoviruses can be
      engineered to attack tumor stem cells, recognized by linage-specific cell surface
      markers, dysfunctional stem cell-signaling pathways, or upregulated oncogenic
      genes. Normal stem cells may possess innate resistance to adenoviruses, as most
      humans have sustained numerous infections with various wild-type serotypes. This
      review focuses on current literature in support of cancer stem cells and
      discusses the possibility of using oncolytic virotherapy for killing these tumor
      initiating cells.

PMID- 18608121
TI  - HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in
      vitro T cell depletion for chronic myeloid leukemia: improved outcomes in
      patients in accelerated phase and blast crisis phase.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      remains the only proven curative therapy for chronic myeloid leukemia (CML), but
      lack of human leukocyte antigen (HLA)-matched sibling or unrelated donors has
      restricted its application. Recently, we developed an effective method for
      haploidentical allo-HSCT achieving comparable outcomes to HLA-identical
      transplantation. AIM: To evaluate the outcomes of CML patients who underwent
      haploidentical allo-HSCT. METHODS: Ninety-three patients were treated with a
      modified busulfan (BU)/cyclophosphamide (CY) 2 regimen, including antithymocyte
      globulin followed by unmanipulated blood and marrow transplantation. RESULTS: Our
      data showed that the cumulative incidence of acute graft-versus-host disease
      (GVHD) was 64.52%, and grade III-IV was 26.45%, 61.79% had chronic GVHD, and
      28.93% had extensive chronic GVHD. Non-relapse mortality varied at 8.72% (100
      days), 20.72% (1 year) and 20.72% (2 years). Probability of 1-year and 4-year
      leukemia-free survival was similar in chronic phase (CP) 1, CP2/CR2, accelerated
      phase, and blast crisis patients. Probability of 4-year overall survival varied
      as 76.5% (CP1), 85.7% (CP2/CR2), 73.3% (accelerated phase), and 61.5% (blast
      crisis). Multivariate analysis indicated that factors affecting transplantation
      outcomes were HLA-B+DR mismatches versus others for II-III acute GVHD and III-IV
      acute GVHD, the stage of disease at transplantation for relapse, and the time
      from diagnosis to transplantation for leukemia-free survival, overall survival,
      and transplantation-related mortality. In our protocol, survival of HSCT for
      advanced CML was similar to stable stage. CONCLUSIONS: For patients lacking an
      HLA-identical related donor, haploidentical relatives are alternative HSCT
      donors.

PMID- 18608122
TI  - Factor VII -323 decanucleotide D/I polymorphism in atrial fibrillation:
      implications for the prothrombotic state and stroke risk.
AB  - There are limited data on the influence of genetic polymorphisms in atrial
      fibrillation (AF) stroke risk. We hypothesized that a functional haemostatic
      polymorphism, that is, the factor VII -323 Del/Ins polymorphism, would influence
      the prothrombotic state associated with AF, as well as stroke risk. Other
      functional polymorphisms were also tested. METHODS: We performed a cross
      sectional study of 119 AF patients, who were compared to 96 patients with stroke
      secondary to AF. In the first patient group, we analysed plasma prothrombin
      fragment 1+2 levels (F1+2, an index of thrombin generation) to reflect the
      prothrombotic state of AF. RESULTS: AF patients carrying the -323 Ins allele had
      lower plasma F1+2 levels (P=0.015). After multivariate analysis adjusted by age,
      sex and clinical risk factors, advanced age and 807C/T polymorphism of
      glycoprotein Ia (GPIa) gene were associated with higher risk of ischaemic stroke
      (OR: 1.06; P=0.003 and OR: 1.91; P=0.025), whilst FVII Ins -323 allele was
      associated with lower stroke risk (OR: 0.41; P=0.017). CONCLUSION: FVII -323 Ins
      allele may modulate the prothrombotic state associated with AF. Despite the small
      sample size, we found that FVII Ins -323 allele could be associated with a lower
      stroke risk in AF, whereas the 807C/T polymorphism may increase the risk.

PMID- 18608123
TI  - Acute hyperglycaemia induces an inflammatory response in young patients with type
      1 diabetes.
AB  - BACKGROUND: Patients with type 1 diabetes (T1D) are at a substantially increased
      risk of cardiovascular disease. Stress-induced hyperglycaemia in turn is shown to
      worsen the prognosis of patients suffering from an acute myocardial infarction.
      However, the mechanisms behind these findings are incompletely known. AIM: To
      investigate whether markers of chronic inflammation, and oxidative stress respond
      to acute hyperglycaemia in patients with T1D. METHODS: The plasma glucose
      concentration was rapidly raised from 5 to 15 mmol/L in 35 males (22 men with T1D
      and 13 age-matched non-diabetic volunteers) and maintained for 2 h. All
      participants were young non-smokers without any signs of diabetic or other
      complications. Markers of chronic inflammation, and oxidative stress were
      analysed in serum/plasma samples drawn at base-line and after 120 min of
      hyperglycaemia. RESULTS: Compared to normoglycaemia, acute hyperglycaemia
      increased the interleukin (IL)-6 concentrations by 39% in patients with T1D
      (P<0.01) and 26% in healthy volunteers (P<0.05). During hyperglycaemia the
      superoxide dismutase concentration was increased by 17% in the healthy volunteers
      (P<0.01) and 5% in the patients with type 1 diabetes (P=NS). The increase in
      tumour necrosis factor (TNF)-alpha was larger in patients with type 1 diabetes
      than in non-diabetic volunteers (35% versus -10%, P<0.05). CONCLUSIONS: This
      study shows that acute hyperglycaemia induces an inflammatory response in
      patients with type 1 diabetes.

PMID- 18608124
TI  - NOC out the fat: a short review of the circadian deadenylase Nocturnin.
AB  - The circadian clock is a conserved internal timekeeping mechanism that controls
      many aspects of physiology and behavior via the rhythmic expression of many
      genes. One of these rhythmic genes, Nocturnin, encodes a deadenylase--a
      ribonuclease that specifically removes the poly(A) tails from mRNAs. This enzyme
      is expressed at high levels during the night in a number of tissues in mammals
      and has recently been implicated in circadian control of metabolism. Targeted
      ablation of this gene in mice results in resistance to hepatic steatosis and diet
      induced obesity. Nocturnin appears to exert rhythmic posttranscriptional control
      of genes necessary for metabolic functions including nutrient absorption,
      glucose/insulin sensitivity, and lipid storage. In the Western world and many
      developing countries, overnutrition--the 'obesity epidemic' suggests that the
      ability to sequester fat stores in times of plenty is no longer advantageous to
      our survival. Understanding the role that the circadian clock plays in
      controlling these metabolic processes is important in treatment and eventual
      eradication of this public health crisis.

PMID- 18608125
TI  - Antithrombotic therapy in patients treated with oral anticoagulation undergoing
      coronary artery stenting. An expert consensus document with focus on atrial
      fibrillation.
AB  - Dual antiplatelet treatment with aspirin and clopidogrel is recommended after
      coronary stenting (PCI-S). There is scant evidence defining optimal post-PCI-S
      antithrombotic therapy in patients with atrial fibrillation (AF) in whom oral
      anticoagulation (OAC) is mandated. To evaluate the safety and efficacy of the
      antithrombotic strategies for this population, we conducted a systematic review
      of the available evidence in patients treated with OAC undergoing PCI-S. AF was
      the most frequent indication for OAC. Post-PCI-S management was highly variable,
      and triple therapy with warfarin, aspirin, and clopidogrel was the most frequent
      and effective combination. Warfarin plus aspirin alone was not sufficiently
      effective in the early period after PCI-S and should not be prescribed. While
      acknowledging that the optimal antithrombotic treatment for patients with AF at
      medium or high thromboembolic risk undergoing PCI-S is currently undefined,
      triple therapy of warfarin, aspirin, and clopidogrel is currently recommended,
      although associated with an increased risk of major bleeding. Restrictive use of
      drug-eluting stent is also recommended, due to the need for prolonged multiple
      drug antithrombotic therapy which may increase the bleeding risk. Whether the
      combination of warfarin and clopidogrel (without aspirin) will preserve efficacy
      and produce less bleeding is an important issue still needing to be addressed.

PMID- 18608127
TI  - Inflammatory angiogenesis in atherogenesis--a double-edged sword.
AB  - The adventitia and the outer layers of media of an atherosclerosis-prone arterial
      wall are vascularized by vasa vasorum. Upon growth of an atherosclerotic lesion
      in the intima, neovascular sprouts originating from the adventitial vasa vasorum
      enter the lesion, the local proangiogenic micromilieu in the lesion being created
      by intramural hypoxia, by increased intramural oxidant stress, and by
      inflammatory cell infiltration (macrophages, T cells and mast cells). The
      angiogenic factors present in the lesions include various growth factors,
      chemokines, cytokines, proteinases, and several other factors possessing direct
      or indirect angiogenic activities, while the current list of antiangiogenic
      factors is smaller. An imbalance between endogenous inducers and inhibitors of
      angiogenesis, with a predominance of the former ones, is essential for the
      development of neovessels during the progression of the lesion. By providing
      oxygen and nutrients to the cells of atherosclerotic lesions, neovascularization
      initially tends to prevent cellular death and so contributes to plaque growth and
      stabilization. However, the inflammatory cells may induce rupture of the fragile
      neovessels, and so cause intraplaque hemorrhage and ensuing plaque
      destabilization. Pharmacological inhibition of angiogenesis in atherosclerotic
      plaques with ensuing inhibition of lesion progression has been achieved in animal
      models, but clinical studies aiming at regulation of angiogenesis in the
      atherosclerotic arterial wall can be designed only after we have reached a firm
      conclusion about the role of angiogenesis at various stages of lesion development
      -good or bad.

PMID- 18608128
TI  - High-density lipoprotein: a fall from grace?
AB  - Based on a plethora of in-vitro and in-vivo research data, high-density
      lipoprotein cholesterol (HDL) has been regarded as universally atheroprotective.
      Consequently, pharmacologically mediated HDL increase has emerged as a potential
      means to improve prevention and treatment of patients with atherosclerotic
      vascular disease. In particular, inhibition of cholesteryl ester transfer protein
      (CETP) was considered a promising strategy. Recently, the unanticipated and
      disappointing results of four large clinical trials with the CETP inhibitor
      torcetrapib have necessitated refinement of the HDL hypothesis. In addition, the
      progressive insight that HDL may actually be predominantly a carrier molecule of
      a wide array of proteins rather than merely a cholesterol-transporter has
      resulted in the interest to look beyond HDL levels alone. Here we will discuss
      the impact of recent developments on the HDL hypothesis as well as the advent of
      even more recent therapeutic developments in the HDL field.

PMID- 18608129
TI  - Molecular genetics of Alzheimer's disease: an update.
AB  - Alzheimer's disease (AD) is a complex disorder of the central nervous system
      (CNS). Molecular genetic research has provided a wealth of information regarding
      the genetic etiology of this devastating disease. Identification and functional
      characterization of autosomal dominant mutations in the amyloid precursor protein
      gene (APP) and the presenilin genes 1 and 2 (PSEN1 and PSEN2) have contributed
      substantially to our understanding of the biological mechanisms leading towards
      CNS neurodegeneration in AD. Nonetheless, a large part of the genetic etiology
      remains unresolved, especially that of more common, sporadic forms of AD. While
      substantial efforts were invested in the identification of genetic risk factors
      underlying sporadic AD, using carefully designed genetic association studies in
      large patient-control groups, the only firmly established risk factor remains the
      epsilon4 allele of the apolipoprotein E gene (APOE). Nevertheless, one can expect
      that with the current availability of high-throughput genotyping platforms and
      dense maps of single-nucleotide polymorphisms (SNPs), large-scale genetic studies
      will eventually generate additional knowledge about the genetic risk profile for
      AD. This review provides an overview of the current understanding in the field of
      AD genetics, covering both the rare monogenic forms as well as recent
      developments in the search for novel AD susceptibility genes.

PMID- 18608131
TI  - The concept of cardiometabolic risk: Bridging the fields of diabetology  and
      cardiology.
AB  - The lack of physical activity and the adoption of poor nutritional habits is the
      major cause of the obesity epidemic that is currently sweeping the world. The
      expansion of adipose tissue mass, especially of the visceral adipose tissue
      depot, is observed in the vast majority of individuals carrying the clinical
      features of the metabolic syndrome, an important (and reversible) risk factor of
      type 2 diabetes and cardiovascular disease. As waist circumference can be used as
      a crude estimate of visceral fat accumulation, its measurement provides further
      information on cardiovascular and type 2 diabetes risk, at any given body mass
      index value. However, an elevated waist circumference might also be the result of
      an increased 'cardioprotective' subcutaneous adipose tissue mass. We have
      proposed that the measurement of plasma triglycerides along with waist
      circumference, the so-called 'hypertriglyceridemic waist' might better quantify
      visceral obesity and its health hazards than waist circumference alone.
      "Hypertriglyceridemic waist" is thought to represent an altered, dysfunctional,
      and highly lipolytic adipose tissue that is a major culprit abnormality behind
      the metabolic syndrome and associated cardiometabolic risk, independently from
      classical cardiovascular disease risk factors such as age, sex, and plasma low
      density lipoprotein (LDL) cholesterol levels.

PMID- 18608132
TI  - Vascular endothelial responses to altered shear stress: pathologic implications
      for atherosclerosis.
AB  - Atherosclerosis preferentially develops at branches and curvatures of the
      arterial tree, where blood flow is disturbed from a laminar pattern, and wall
      shear stress is non-uniform and has an irregular distribution. Vascular
      endothelial cells (ECs), which form an interface between the flowing blood and
      the vessel wall, are exposed to blood flow-induced shear stress. There is
      increasing evidence suggesting that laminar blood flow and sustained high shear
      stress modulate the expression of EC genes and proteins that function to protect
      against atherosclerosis; in contrast, disturbed blood flow and the associated low
      and reciprocating shear stress upregulate proatherosclerotic genes and proteins
      that promote development of atherosclerosis. Understanding of the effects of
      shear stress on ECs will provide mechanistic insights into its role in the
      pathogenesis of atherosclerosis. The aim of this review article is to summarize
      current findings on the effects of shear stress on ECs, in terms of their signal
      transduction, gene expression, structure, and function. These endothelial
      cellular responses have important relevance to understanding the
      pathophysiological effects of altered shear stress associated with
      atherosclerosis and thrombosis and their complications.

PMID- 18608135
TI  - Short-term electrophysiological effects of losartan, bisoprolol, amlodipine, and
      hydrochlorothiazide in hypertensive men.
AB  - BACKGROUND AND AIM: Hypertension-induced left ventricular structural remodelling
      associates with repolarization abnormalities. We investigated if antihypertensive
      drugs can modulate ventricular repolarization. METHODS: A total of 183
      hypertensive men received for 4 weeks drugs (losartan 50 mg, bisoprolol 5 mg,
      amlodipine 5 mg, hydrochlorothiazide (HCTZ) 25 mg) in a randomized order,
      separated by 4-week placebo periods. Electrocardiograms (ECG) were recorded at
      the end of placebo and drug periods. Measurements of repolarization duration (QT
      intervals), repolarization heterogeneity (T-wave peak to T-wave end (TPE)
      intervals), and T-wave morphology (T-wave principal component analysis (PCA)
      ratio, T-wave morphology dispersion (TMD), and total cosine R-to-T (TCRT)) during
      each drug were compared to placebo measurements. RESULTS: Losartan and bisoprolol
      shortened maximum and mean rate-adjusted QT intervals as well as mean TPE
      interval, decreased TMD, and increased TCRT. Losartan also shortened precordial
      maximum TPE interval and decreased PCA ratio. Amlodipine had no repolarization
      effects, whereas HCTZ prolonged precordial maximum TPE interval and mean TPE
      interval. CONCLUSION: Losartan and bisoprolol have beneficial short-term ECG
      repolarization effects. Amlodipine seems to have no repolarization effects. HCTZ
      seems to prolong the ECG TPE interval, potentially reflecting increased
      repolarization heterogeneity. These findings show that antihypertensive drugs may
      relatively rapidly and treatment-specifically modulate ECG markers of ventricular
      repolarization.

PMID- 18608136
TI  - Factors associated with traumatic symptoms and internalizing problems among
      adolescents who experienced a traumatic event.
AB  - The aim of the present study was to identify factors that are related to the
      traumatic symptoms and problem behavior among adolescents who experienced the New
      Years fire in 2001 in Volendam, The Netherlands. Three groups of factors were
      considered: pre-trauma (personality and coping), trauma-related (physical and
      emotional proximity to disaster), and post-trauma factors (received social
      support). Forty-five adolescents completed the questionnaire. Two years after the
      disaster, these adolescents experienced significant traumatic stress reaction
      (70% within the clinical range) and showed clinically significant levels of
      internalizing problems (37%). Pre-trauma, individual factors were identified as
      the most important predictors of distress, followed by received social support.
      The indicators of physical and emotional proximity to disaster explained little
      variance in distress.

PMID- 18608137
TI  - The role of workload and driver coping styles in predicting bus drivers' need for
      recovery, positive and negative affect, and physical symptoms.
AB  - A survey was conducted on a sample of 159 Australian bus drivers to determine the
      extent to which workload and self-reported driver coping styles predicted their
      subjective health status. The model that was proposed incorporated the hours
      spent driving as a measure of workload, both adaptive and maladaptive driver
      coping styles, and self-report measures of need for recovery (i.e., fatigue),
      positive and negative affect (PA and NA), and physical symptoms. The results of
      hierarchical regression analyses revealed that the workload was a significant
      predictor of drivers' need for recovery, but not of their PA and NA nor of their
      physical symptoms. Need for recovery was in turn a significant predictor of PA
      and NA and of their physical symptoms, indicating that it mediates the influence
      of workload on PA and NA and physical symptoms. Two maladaptive coping strategies
      added to the prediction of need for recovery, as well as to the prediction of NA,
      even after controlling for the influence of need for recovery. One adaptive
      coping strategy added to the prediction of PA. Strategies for management of
      fatigue in bus drivers should focus on the assessment and remediation of
      maladaptive coping strategies which impact of drivers' need for recovery, which
      in turn predicts PA and NA and physical symptoms.

PMID- 18608141
TI  - Workplace fairness and emotional exhaustion in Nigeria police: the moderating
      role of gender.
AB  - This study examined the moderating role of gender in the relationship between
      perceived workplace fairness and reported level of emotional exhaustion among a
      sample of Nigeria police. A total of 214 participants took part in the cross
      sectional survey. Results of the moderated hierarchical regression analysis
      provided support for gender as a moderating variable in the relationship between
      perceived workplace fairness and emotional exhaustion, such that perceived
      workplace fairness was a stronger predictor of emotional exhaustion among male
      police than for female police. The practical implications for the management of
      emotional exhaustion in general, and for the Nigeria police in particular, were
      emphasized.

PMID- 18608143
TI  - Teaching Latino parents to support the multi-symbol message productions of their
      children who require AAC.
AB  - Many children who require augmentative and alternative communication (AAC) have
      difficulties shifting from the single- to multi-symbol stage of language
      development. Ensuring that children who use AAC receive evidence-based
      interventions to address this problem is critical. Furthermore, there has been
      little AAC treatment efficacy research to date that addresses the needs of
      multicultural populations, particularly those of Latino children who use AAC and
      their families. To address these issues, the current investigation used a mixed
      methodology, which included a focus group to determine if any changes needed to
      be made to an existing instructional program; and a single subject, multiple
      probe, across participants design to evaluate the effects of a caregiver
      instructional program on the multi-symbol utterance productions of Latino
      children who used AAC. Specifically, a cognitive strategy instructional approach
      that has been used to teach turn-taking skills to both Caucasian and African
      American children who use AAC was modified and used to teach caregivers how to
      support the production of their children's multi-symbol messages. In order to
      foster emergent literacy skills, caregivers implemented the strategy during book
      reading activities. Focus group results revealed that changes to the
      instructional program may be required for some Latino families. With regard to
      the instructional program, all caregivers successfully learned to use the
      instructional strategy, and all children increased their use of multi-symbol
      messages. Research and clinical implications of the findings are discussed.

PMID- 18608145
TI  - An investigation of aided language stimulation: does it increase AAC use with
      adults with developmental disabilities and complex communication needs?
AB  - A single subject ABAB design was used to determine the efficacy of aided language
      stimulation to teach the use of AAC techniques to adults with developmental
      disabilities. Sixteen participants were divided into two equal groups. In each
      group, half of the participants were able to communicate functionally using
      spoken language and half had complex communication needs and did not have
      functional, symbolic communication systems. Each group met twice weekly for 30
      min per session. Researchers modeled the use of AAC and followed scripts during
      music-based interventions. Sessions focused on social greetings, choosing songs
      to play, learning words and movements for the songs, and discussing the songs.
      Participants were encouraged to interact with each other and to facilitate each
      other's communications. Results suggest that responsiveness and use of AAC
      increased for all participants with complex communication needs.

PMID- 18608144
TI  - The effect of context priming and task type on augmentative communication
      performance.
AB  - Augmentative and Alternative Communication (AAC) devices include special purpose
      electronic devices that generate speech output and are used by individuals to
      augment or replace vocal communication. Word prediction, including context
      specific prediction, has been proposed to help overcome barriers to the use of
      these devices (e.g., slow communication rates and limited access to situation
      related vocabulary), but has not been tested in terms of effects during actual
      task performance. In this study, we compared AAC device use, task performance,
      and user perceptions across three tasks, in conditions where the AAC device used
      either was, or was not, primed with task specific vocabularies. The participants
      in this study were adults with normal physical, cognitive, and communication
      abilities. Context priming had a marginally significant effect on AAC device use
      as measured by keystroke savings; however, these advantages did not translate
      into higher level measures of rate, task performance, or user perceptions. In
      contrast, there were various statistically significant process and performance
      differences across task type. Additionally, results for two different emulations
      of human performance showed significant keystroke savings across context
      conditions. However, these effects were mitigated in actual performance and did
      not translate into keystroke savings. This indicates to AAC device designers and
      users that keystroke-based measures of device use may not be predictive of high
      level performance.

PMID- 18608146
TI  - A survey of memory clinics in New Zealand.
AB  - OBJECTIVE: The aim of this survey was to identify all the publicly funded memory
      clinics in the 21 District Health Boards (DHBs) in New Zealand. METHOD:
      Information on the provision of memory clinics was obtained by emailing the old
      age psychiatrists' group and making telephone contact with clinicians working in
      old age psychiatry/geriatric services. A brief structured questionnaire was
      completed by the memory clinic lead clinicians. RESULTS: There are eight memory
      clinics in New Zealand, funded equally between mental health services and
      geriatric medicine. However, there is variability in the provision of memory
      clinics in the medium and smaller sizedDHBs and inconsistency in the level of
      funded staff across DHBs. CONCLUSIONS: Acknowledgement of the value of memory
      clinics within a national service framework is needed, with appropriate
      benchmarking of funding. This would ensure improved access, including for rural
      and remote areas of New Zealand.

PMID- 18608147
TI  - Set up to fail? Consumer participation in the mental health service system.
AB  - OBJECTIVE: The aim of this paper is to present the findings of a survey of
      consumers of mental health services who are working (in either paid or unpaid
      positions) in NSW Health and in the Non Government Organisation sector in NSW.
      METHOD: A survey was distributed through the NSW Consumer Advisory Group
      newsletter to elicit the roles and assess the training needs of consumer
      employees, as well as those who were working in voluntary capacities as consumer
      representatives, within the mental health system in NSW. RESULTS: Many mental
      health consumers have been placed in the untenable position of being engaged in
      representation and/or advocacy roles with unclear job descriptions and no
      training. The majority of consumers want a code of ethics and performance
      standards for consumer workers. CONCLUSIONS: The rhetoric of consumer
      participation is not matched by effective and timely strategies that ensure that
      consumer involvement is underpinned by relevant training and supportive
      infrastructure. The goal of meaningful consumer participation in mental health
      services, as outlined in policy, is yet to be achieved.

PMID- 18608148
TI  - Can music preference indicate mental health status in young people?
AB  - OBJECTIVE: In the aftermath of the double suicide of two teenage girls in 2007,
      the media linked the themes of 'emo' music and the girls' mental state. But it is
      not just emo music that has been the subject of scrutiny by the media. Rap music,
      country, and heavy metal have also been blamed for antisocial behaviours
      including violence, theft, promiscuity and drug use. It remains an important
      research and clinical question as to whether music contributes to the acting out
      of behaviours described in the music lyrics or whether the preferred music
      represents the already existing behavioural tendencies in the subject. This paper
      surveys and discusses the relevant literature on music preference and adolescent
      music listening behaviours, and their links with adolescent mental health.
      CONCLUSION: Studies have found a relationship between various genres of music and
      antisocial behaviours, vulnerability to suicide, and drug use. However, studies
      reject that music is a causal factor and suggest that music preference is more
      indicative of emotional vulnerability. A limited number of studies have found
      correlations between music preference and mental health status. More research is
      needed to determine whether music preferences of those with diagnosed mental
      health issues differ substantially from the general adolescent population.

PMID- 18608149
TI  - Anxiety disorders no more?
AB  - OBJECTIVE: The aim of this article was to critically examine options for the
      future classification of the current Diagnostic and Statistical Manual (DSM)
      group of anxiety disorders. CONCLUSIONS: There is a strong trend towards the
      narrowing of the current DSM group of anxiety disorders and to the adopting of a
      different name for it. A future conceptualization of the conditions currently
      classified as anxiety disorders will be useful to the extent that it espouses a
      longitudinal diagnostic approach and acknowledges a lack of clear boundaries
      between anxiety and related disorders.

PMID- 18608150
TI  - "If there is a doctor aboard this flight. . .": issues and advice for the
      passenger-psychiatrist.
AB  - OBJECTIVE: On several occasions, the author has responded to requests for medical
      assistance while travelling by air. This paper examines the various issues when a
      passenger-psychiatrist is confronted with an in-flight medical emergency.
      CONCLUSIONS: A range of medical problems can present during air travel. A review
      of the available literature on a doctor's obligations when confronted with an in
      flight medical emergency is provided. Guidelines for the passenger
      psychiatrist,who at some stage is likely to encounter such a circumstance, are
      offered.

PMID- 18608151
TI  - The mental health literacy of rural adolescents: Emo subculture and SMS texting.
AB  - OBJECTIVE: This study sought to explore the mental health literacy of adolescents
      living in a rural area in Australia through in-depth, semi-structured interviews,
      with a view to identifying areas for further research and making recommendations
      for improved education programs around mental health. METHOD: Nine Year 10
      students (two boys and seven girls) from a rural secondary school in South
      Australia read two vignettes, one portraying depression and the other
      schizophrenia. Semi-structured individual interviews that focussed on the
      vignettes were audio-taped, transcribed and analysed for thematic content.
      RESULTS: The data yielded a number of main themes, many of which have been
      previously identified in the literature. Two new findings also emerged. These
      were the role of Emo subculture and dealing with distress, and the value of
      confiding in another person through short message service (SMS) texting.
      CONCLUSIONS: The impact of Emo subculture and SMS texting on mental health
      literacy requires further exploration. It is suggested that these two findings
      are not confined to rural youth, but may have national and international
      relevance.

PMID- 18608152
TI  - Reflections of a retiring examiner.
AB  - OBJECTIVE: This article is a transcript of an invited talk given to the Victorian
      Branch of the Australian and New Zealand Association of Psychiatrists in Training
      in February 2008, as part of an annual function designed to assist trainee
      psychiatrists as they prepare for the Royal Australian and New Zealand College of
      Psychiatrists' clinical examination. Six points of reflection are discussed from
      the perspective of the examiner. The talk focuses on the Observed Clinical
      Interview component of the clinical examination as this is where many candidates
      seem to struggle to meet the required standard. CONCLUSION: While specific
      examination preparation is essential, breadth of clinical experience, supervision
      and an opportunity to think and reflect on one's learning seem to be essential
      elements in success at these high stakes examinations.

PMID- 18608153
TI  - Consumer-clinician co-taught training about borderline personality disorder.
AB  - OBJECTIVE: The aim of this paper is to provide further outcome data on a novel
      consumer-clinician co-taught borderline personality disorder training program.
      METHOD: Participants (n=216) who attended consumer-clinician co-taught borderline
      personality disorder training had their ratings of the training compared to
      ratings of participants who attended the previous clinician-only borderline
      personality disorder training. RESULTS: Mean training ratings of the consumer
      clinician co-taught borderline personality disorder trainings were 37 percentile
      points higher (77th vs 40th percentile) than the ratings of the previous
      clinician-only borderline personality disorder training, which already had
      evidence of effectiveness. CONCLUSION: Data confirm preliminary findings that
      adding a consumer-presenter to training adds considerable value.

PMID- 18608155
TI  - Community Treatment Orders in Victoria: a clinico-ethical perspective.
AB  - OBJECTIVE: The aim of this paper is to outline the impact of Community Treatment
      Orders over a 20-year period on service delivery and clinical practice in
      Victoria. CONCLUSIONS: Community Treatment Orders, as utilized in Victoria, have
      undermined optimal service delivery and supported paternalistic, reductionistic
      clinical practice. The psychiatric profession has failed to advocate adequately
      for better mental health resourcing and human rights protection of those subject
      to Community Treatment Orders.

PMID- 18608154
TI  - Interventions to address violence associated with mental illness.
AB  - OBJECTIVES: The aim of this paper is to consider the association between mental
      illness and violence, and discuss broad intervention approaches. CONCLUSION: The
      necessary elements of intervention to reduce violence by the mentally ill are
      holistic care, access to services and, where necessary, legal leverage. In the
      custodial setting, this includes screening, early intervention and treatment in
      prison, and assertive post-release case management to divert mentally ill
      offenders away from substance use and to support their return to the community.
      In the community setting, active case management, including access to inpatient
      beds and co-ordination between mental health services and other agencies, is
      crucial to providing continuity of care for patients at risk of violence in the
      community.

PMID- 18608156
TI  - Hallucinations in adolescent inpatients with post-traumatic stress disorder and
      schizophrenia: similarities and differences.
AB  - OBJECTIVE: This study compares the phenomenology of hallucinations in a series of
      hospitalized adolescents diagnosed with post-traumatic stress disorder (PTSD) and
      schizophrenia. METHODS: Subjects admitted to a tertiary adolescent inpatient unit
      were screened for hallucinations. Those reporting hallucinations were asked
      standardized questions relating to these experiences. Hallucinations in subjects
      with a primary diagnosis of schizophrenia or PTSD were compared. RESULTS:
      Hallucinations in both schizophrenia and PTSD have similar form and content.
      Frequent, vivid, realistic, external hallucinations occurred in both disorders.
      Hallucinations in PTSD were usually derogatory and related to self-harm, but not
      direct reflections of traumatic events. Patients with PTSD reported greater
      emotional distress, self-harm and suicidal ideation than those with
      schizophrenia. CONCLUSIONS: This case series suggests that the phenomenology of
      hallucinations in adolescents with schizophrenia and PTSD is similar.

PMID- 18608157
TI  - The Wild West: rural and remote psychiatry training in North Western Australia.
AB  - OBJECTIVE: The author reflects on his rural psychiatric training in North Western
      Australia, having gained over 2 years' experience as a basic and advanced trainee
      in this setting. The unique rewards and benefits of rural training are discussed
      along with the challenges of working in an isolated setting with resource
      constraints. CONCLUSIONS: Rural and remote training remains a stimulating and
      professionally satisfying experience that is under-utilized by many trainees. In
      spite of most training requirements being able to be met in this setting,
      trainees are reluctant to undertake this valuable and enjoyable training
      experience. Trainees are encouraged to consider this opportunity to be upskilled
      and getting involved on a more personal level with patients, families and general
      practitioners, thereby enhancing their clinical skills and shaping their
      professional identity as future psychiatrists.

PMID- 18608158
TI  - Personality, gender and medico-legal matters in medical practice.
AB  - OBJECTIVES: The aim of this paper was to explore the relationship between the
      personality traits of Australian General Practitioners (GPs) and their gender,
      work practice arrangements, and history of medico-legal matters. METHODS: A cross
      sectional self report survey was mailed to 1239 GPs. There were 566 respondents
      (45.7% response rate to survey). The survey assessed personality traits (using
      the Eysenck Personality Questionnaire), demographic and practice information, and
      history of medico-legal matters with any medical defence organization. The number
      and type of medico-legal matters was also extracted from the UNITED Medical
      Protection database. RESULTS: Male respondents had significantly higher
      psychoticism scores than females (p<0.001), and females had significantly higher
      neuroticism scores than males (p<0.01), as in community samples. However, for GPs
      who worked more than 48 hours per week, there were no gender differences in
      personality trait scores. Solo practitioners and non-solo practitioners did not
      differ on personality scores. Proceduralists and non-proceduralists did not
      differ on personality scores. However, a higher proportion of proceduralists
      experienced a medico-legal matter than non-proceduralists (p<0.001). There was a
      positive correlation between extraversion scores and doctors who attended peer
      review (p<0.001). There was no difference in the numbers of medico-legal matters
      for doctors who attended peer review. Males who self reported a medico-legal
      matter had higher neuroticism scores than the males who did not report medico
      legal matters. This was not the case for females. For males, this pattern was not
      replicated when considering data from UNITED. CONCLUSIONS: The known demographic
      and practice factors that differ for doctors having a medico-legal matter are
      replicated here--being male, a proceduralist and working longer hours. There is
      not a consistent pattern regarding personality traits and medico-legal matters.

PMID- 18608159
TI  - Metaphor, meaning and psychiatry.
AB  - OBJECTIVE: The aim of this paper is to examine the scientific and cognitive role
      of metaphor and the use of metaphor in the conceptualization of depression as an
      example of mental illness. CONCLUSIONS: Metaphors from the creative arts have
      been used to support existing psychiatric diagnostic concepts. The existing
      concepts are themselves built on embedded metaphors now treated as literal facts.
      The choice of metaphor dictates not only the description of the condition but
      also its treatment and research. The use of unacknowledged and unchanging
      metaphors in current diagnostic practice affects progress in knowledge and
      practice. Some alternative borrowings of basic metaphors are provided.

PMID- 18608161
TI  - Continuing professional development for Australian rural psychiatrists by
      videoconference.
AB  - OBJECTIVE: The Rural Special Interest Group (RSIG) of the Royal Australian and
      New Zealand College of Psychiatrists provided a program of educational meetings
      for psychiatrists and trainees in rural locations to decrease professional
      isolation and facilitate opportunities to obtain credit for continuing
      professional development (CPD) purposes in ongoing professional registration. A
      pilot peer review group by videoconference was also implemented in Western
      Australia, to provide peer review for psychiatrists working in isolation. METHOD:
      Six national interactive videoconferenced education seminars were provided. The
      membership was polled prior to the program for topic preferences and requested
      speakers, who were subsequently approached to present the seminars. A West
      Australian peer review group was formed, involving psychiatrists from five
      different rural locations and one psychiatrist from the metropolitan area.
      RESULTS: National seminars were attended by 106 individuals (67% consultant
      psychiatrists, 17% trainees and 16% allied health professionals). Evaluation
      demonstrates favourable views of the content and quality of the presentations and
      impact on practice patterns. CONCLUSIONS: Attendance at seminars via
      videoconferencing provided rural psychiatrists with opportunities to obtain CPD
      credit without the need to travel, providing a cost-effective alternative for
      accessing education. Involvement enabled interaction among peers throughout
      Australia, alleviating professional isolation and generating networking
      opportunities. The West Australian peer review group demonstrated sustainability
      with a commitment to continuation and positive impact on practice.

PMID- 18608162
TI  - Changes to inpatient consultation-liaison psychiatry service delivery over a 7
      year period.
AB  - OBJECTIVE: The aim of this paper was to examine the effect of changes to a
      consultation-liaison (C-L) service at Maroondah Hospital on referral and service
      delivery patterns across a period of 7 years. There is no national benchmarking
      of C-L service. Local services respond to local political and service demands.
      There have been significant changes to the C-L service at Maroondah Hospital
      between 1999 and 2006. During the intervening years, psychogeriatric referrals
      have been included and gazetting of general hospital beds has resulted in
      detention of patients under the Mental Health Act (MHA). METHOD: Clinical audit
      data from assessments by the C-L service during the above period were entered
      into a database and analysed. RESULTS: The annual referral rate increased as did
      the mean age of referred patients. The main reason for referral changed from
      suicide evaluation and history of psychotic symptoms to depression. Referral lag
      time did not change significantly. A higher proportion of patients received a
      single consultation and a greater number required psychiatric inpatient care.
      CONCLUSION: The nature of referral changed towards older, sicker patients and
      away from younger, suicidal patients which, together with an increased referral
      rate, significantly increased demand on available resources.

PMID- 18608163
TI  - Risk assessment and management in practice: the Forensicare Risk Assessment and
      Management Exercise.
AB  - OBJECTIVE: There is an emerging consensus that the assessment and management of
      adverse outcomes in mental health, such as violence and self harm, is best
      achieved by approaches which incorporate validated tools using "structured
      professional judgement". Although several useful tools have emerged from the
      literature, there is no clear consensus on the best way to integrate these with
      clinical practice. This paper describes a framework, the Forensicare Risk
      Assessment and Management Exercise (F.R.A.M.E.), employed by a statewide
      community forensic mental health service, which incorporates two structured
      professional judgement tools, and explicitly integrates these into case
      management and psychiatric treatment. The potential benefits of the framework are
      discussed in the context of contemporary trends in risk assessment and
      management. CONCLUSIONS: The F.R.A.M.E. appears to assist with the task of
      integrating risk assessment with clinical management. Formal evaluative research
      is indicated before it can be recommended for use by other services.

PMID- 18608164
TI  - Developing integrated models of care within the youth Alcohol and Other Drug
      sector.
AB  - OBJECTIVE: The aim of this paper is to describe an initiative in Victoria,
      Australia, aimed at improving the detection and management of co-occurring mental
      health issues within the youth Alcohol and Other Drug (AOD) sector. CONCLUSIONS:
      Over the past 4 years, in partnership with local youth AOD services, we have
      developed a successful service model that addresses co-occurring mental health
      issues within the youth AOD sector. However, such capacity-building requires the
      full support of workers and senior management, and a cultural shift whereby the
      assessment and management of mental health issues are seen as a priority and core
      service issue. The capacity-building process was facilitated by embedding
      experienced mental health clinicians within each service to support and implement
      the initiative. This model offered learning opportunities through the modelling
      of relevant skills and the provision of 'on-the-job' training. Such approaches
      demonstrate that integrated models of care can be delivered within youth AOD
      services, although further research is needed to determine their effectiveness.

PMID- 18608165
TI  - The Adolescent Intensive Management Team: an intensive outreach mental  health
      service for high-risk adolescents.
AB  - OBJECTIVE: The aim of this paper was to describe the Adolescent Intensive
      Management (AIM) team at the Austin Child and Adolescent Mental Health Service
      (CAMHS), a unique model of intensive outreach service with high-risk and
      difficult-to-engage adolescents, and describe the profile of clients referred to
      it. METHOD: This study used a retrospective review of clients' data, collected
      through file audit, over a 12-month period. RESULTS: The result of the study
      showed that a 100% retention rate of adolescents with complex social, emotional
      and mental health needs is possible in a flexible and multi-system approach to
      service provision. CONCLUSION: Clients referred to the CAMHS' AIM team displayed
      a pattern of multiple risk factors and comorbidities. Low caseload of 8-10
      clients per clinician allowed flexibility and a level of intensity to make any
      necessary changes in service provision to better suit the client's needs. The
      majority of clients showed improvement in functioning following intervention by
      the team.

PMID- 18608166
TI  - Psychiatry in the land of the Sphinx: is an overseas elective justified?
AB  - OBJECTIVE: The aim of this paper is to provide a descriptive account of a 6-month
      sabbatical in Egypt to highlight the diversity of benefits in incorporating such
      activities within psychiatric training programs. CONCLUSIONS: An overseas
      elective offers an exciting practical opportunity to broaden one's experience of
      transcultural psychiatry and obtain a perspective on mental illness and its
      cultural variations. It also promotes an understanding of health service
      management in low and middle income countries and offers the opportunity to
      contribute to their healthcare at minimal cost. However, the elective needs to be
      undertaken at an optimal period of a psychiatrist's career and with minimal
      disruption to local services. Training schemes and employers could provide more
      opportunities for interested trainees, with specified projects and aims in mind,
      to undertake such electives so that they can begin to develop expertise in
      treating a particular cultural group. In turn, this would go a long way to
      producing culturally capable psychiatrists for the wide range of ethnic
      minorities in Australia.

PMID- 18608167
TI  - Suicide and reputation damage.
AB  - AIM: This paper uses the public record to explore the relationship between
      reputation damage and suicide. METHOD: The public record of the last 20 years was
      examined for examples of individuals without evidence of mental disorder who
      suffered actual or threatened reputation damage and suicided shortly thereafter.
      RESULTS: Fifteen individual cases were identified; 18 additional cases, less
      comprehensively detailed, were mentioned in reports of The Wood Royal Commission
      and Operation Auxin. All cases were male. Of the 15 individual cases, the average
      age was 55 years, with a range of 40 to 76 years. The available details of the 18
      additional cases were consistent with these findings. CONCLUSION: Middle-aged
      males without clear evidence of mental disorder, who suffer actual or threatened
      reputation damage, may be at increased risk of suicide. Naming and shaming needs
      to be conducted with caution.

PMID- 18608168
TI  - The Wellness Recovery Action Plan (WRAP): workshop evaluation.
AB  - OBJECTIVE: This study evaluated the delivery of a series of workshops on mental
      health recovery. The aims were to determine if the workshops changed
      participants' attitudes and knowledge about recovery, if there were any
      differences in views between consumers and health professionals of mental health
      services, and how the delivery and content of the program could be improved.
      METHODS: A total of 187 consumers and health professionals from mental health
      services attended a workshop based on the Wellness Recovery Action Plan (WRAP).
      Questionnaires were administered before and after the workshop. RESULTS: There
      was a significant change in total attitudes and knowledge about recovery
      (p<0.001) in the expected direction, with no differences between consumers and
      health professionals. The majority of participants found the workshop useful, and
      the majority of comments were positive. CONCLUSIONS: This study provides
      preliminary support for the use of WRAP to change consumers' and mental health
      professionals' knowledge and attitudes about recovery.

PMID- 18608169
TI  - Patient and staff perspectives on the use of seclusion.
AB  - OBJECTIVES: This paper investigates the perceptions and experience of patients
      and staff on the use of seclusion in psychiatric services. METHOD: A purpose
      designed questionnaire was distributed to staff and patients in a general adult
      mental health service. RESULTS: Staff and patients both attributed more negative
      than positive feelings to patients' experience of seclusion. CONCLUSIONS:
      Monitoring and evaluation of the use of seclusion may be insufficient to prevent
      or ameliorate its emotional impact. More comfortable alternatives to seclusion
      need to be utilized whenever possible.

PMID- 18608170
TI  - The Blue Card: a hand-held health record card for mental health consumers with
      comorbid physical health risk.
AB  - OBJECTIVE: We aimed to determine the effectiveness of a hand-held record (the
      'Blue Card') for seriously mentally ill consumers by investigating effects on
      consumer knowledge of physical health risk factors, consumer involvement in care
      and communication with healthcare professionals. METHOD: Consumers were given and
      educated in the use of the Blue Card, which contained information regarding their
      physical health. Consumers completed a pre- and post-knowledge questionnaire and
      commented on the effectiveness of the Blue Card with respect to their knowledge
      of physical health risks. RESULTS: Statistically significant improvements in
      consumer knowledge were shown at the 3-month follow-up, with high retention of
      the Blue Card being demonstrated. Consumers that used the card described their
      use of the card positively. CONCLUSIONS: The results are very encouraging.
      Further studies of this low-cost intervention are warranted to establish its
      effectiveness and utility.

PMID- 18608172
TI  - Side effects of second-generation antipsychotics: the experiences, views and
      monitoring practices of Australian child psychiatrists.
AB  - OBJECTIVE: The aim of this study was to ascertain the experiences, views and
      monitoring practices of Australian child psychiatrists regarding the metabolic
      and other side effects of second-generation antipsychotics (SGAs). METHOD: A 19
      item questionnaire was posted to all members of the RANZCP Faculty of Child and
      Adolescent Psychiatry living in Australia. RESULTS: Of the 290 eligible members
      of the Faculty of Child and Adolescent Psychiatry, 126 (43%) returned a useable
      survey. SGAs are commonly prescribed for a range of disorders. The majority of
      respondents expressed a high level of concern regarding weight gain and other
      metabolic side effects. Weight gain was the most frequently observed and
      monitored side effect in clinical practice. Other side effects were observed and
      monitored to a variable extent. Notably, monitoring practices did not parallel
      psychiatrists' reported level of concern or knowledge regarding weight gain and
      metabolic side effects,nor coincide with published recommendations. CONCLUSIONS:
      Further research is required into the use, efficacy, side effects and monitoring
      of SGAs in children and adolescents, and there is a need to ensure that
      monitoring guidelines are implemented in clinical practice. This need is
      heightened by the likelihood that our data on clinicians' practice, which is
      based on their perceptions, may overestimate what actually occurs.

PMID- 18608173
TI  - Gene expression profiles at different stages of collagen-induced arthritis.
AB  - The molecular basis to autoimmune arthritis is unclear. To identify candidate
      molecules that may be involved in the development and progression of collagen
      induced arthritis (CIA), an animal model for human rheumatoid arthritis, we used
      microarray and real-time PCR assays to examine the gene expression profiles at
      the onset, peak and decline phase of CIA. Our results showed that, of the 514
      immune-related genes assayed in microarrays, fifty-eight genes showed
      differential expression with thirty-one up-regulated and twenty-seven down
      regulated in CIA joints, in comparison to normal joint tissue. By real-time PCR,
      expression of some chemokines/chemokine receptors, such as CCR1, CXCR4, CXCL13
      and MCP1, showed significantly elevated in the inflamed joints. Quite a few genes
      were significantly up- or down-regulated at the peak time point, which indicates
      their roles in the progression of the disease. In addition, the expression levels
      of some genes remained significantly elevated at all stages of the disease. These
      gene expression profiles may help understand the pathogenesis of the disease.

PMID- 18608174
TI  - Interferon-tau inhibits the development of diabetes in NOD mice.
AB  - Interferon-alpha (IFN-alpha) inhibits the development of diabetes in animal
      models of autoimmune diabetes. However, the mechanism of the action is not fully
      understood and drug toxicity could limit its potential clinical utility.
      Interferon-tau (IFN-tau) is another type 1 interferon, which has less toxicity
      but may have different biologic activity than IFN-alpha. This study explores the
      effect of IFN-tau on the diabetic process in non-obese diabetic (NOD) mice. IFN
      tau by intraperitoneal, subcutaneous, or oral routes of administration decreased
      the development of spontaneous diabetes in NOD mice. Islet inflammation was
      decreased 50%. IFN-tau administration to recipient mice prevented the development
      of passively transferred and cyclophosphamide accelerated diabetes. IFN-tau
      treatment also decreased anti-islet effector activity of NOD splenic cells.
      Immunoregulatory activity of splenic cells was augmented by IFN-tau
      administration as was the number of splenic CD25+CD4+ cells. Concanavalin A (Con
      A)-induced release of IFN-gamma was decreased in spleen cells from IFN-tau
      treated mice. In conclusion, IFN-tau inhibits spontaneous autoimmune diabetes and
      passively transferred diabetes in the NOD mouse. This diabetes sparing activity
      may be due to an induction of regulatory cells, possibly CD25+CD4+ T cells, which
      in turn inhibit anti-islet effector cell activity and the development of
      insulitis and diabetes. Due to the lower drug toxicity, IFN-tau could be a better
      drug candidate than IFN-alpha for experimental clinical trials.

PMID- 18608175
TI  - Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and
      ameliorated by Nippostrongylus brasiliensis infections.
AB  - Rheumatoid arthritis is an autoimmune disease that affects human beings
      worldwide. Infections have been associated to autoimmune diseases because their
      ability to induce a dominant cytokine response. Joint inflammation has been
      related to Th1 response because they induce high expression of proinflammatory
      cytokines TNF-alpha, IL-1, IFN-gamma. MRL/lpr mice spontaneously develop an
      autoimmune disease affecting joints, kidneys, etc. We compared incidence and
      severity of arthritis, antibody response, cytokine production, in mice infected
      with bacteria or helminthes in the Murphy Roths Large (MRL)lpr mice. Infections
      with helminthes Heligmosomoides polygyrus, Nippostrongylus brasiliensis or
      bacteria Nocardia brasiliensis and Staphylococcus aureus were studied. IL-4, IFN
      gamma and IgG1, IgG2a antibody productions were determined. IFN-gamma was
      increased in all groups, the highest production was observed after bacterial
      infection; IL-4 production was higher after helminthes infection. IgG1 sera
      levels were increased in the helminthes infected group. IgG2a sera concentration
      was stimulated by bacterial infection. The histopathology showed that 100% of
      bacterial infected mice developed arthritis and severe tissue damage such as
      cartilage erosion and bone destruction. Animals infected with parasites showed a
      decreased incidence and severity of arthritis. Severity of tissue damage in
      joints is correlated with increased numbers of lymphocytes and macrophages
      immunoreactive to proinflammatory cytokines.

PMID- 18608176
TI  - Susceptible and protective endothelial nitric oxide synthase gene polymorphism in
      alopecia areata in the Kuwaiti population.
AB  - Alopecia areata (AA) is a chronic inflammatory disease with evidence of T-cell
      involvement that causes hair follicle "immune privilege collapse". Nitric
      monoxide was shown to contribute in the pathogenesis of AA. We are investigating
      evidence for the association of eNOS gene polymorphism with AA. Genomic DNA was
      extracted from 176 subjects, 87 Kuwaiti AA patients and 89 matched (for
      ethnicity, gender and age) healthy controls. A variable number tandem repeat
      (VNTR) located in intron-4 of the eNOS gene consisting of either four or five (27
      base pair) repeats was analyzed by polymerase chain reaction and electrophoresis
      fragment analysis using ABI 3100 genetic analyzer. Haploview and GenePOP software
      were used for data analysis. A significant association was found between the
      intron-4 27 bp-VNTR and AA, where 4b was identified as the risk allele had
      (chi(2) = 4.42, p = 0.035, OR = 2.03). Genotype (4b/4b) showed a significant
      association with susceptibility to AA and have a frequency of 22% higher in AA
      patients than in healthy controls (71 vs 49%) and a chi(2) = 6.39, (p = 0.011, OR
      = 2.63). We report a significant association of a polymorphism within the eNOS
      gene and susceptibility to AA.

PMID- 18608177
TI  - Antigenic complementarity between coxsackie virus and streptococcus in the
      induction of rheumatic heart disease and autoimmune myocarditis.
AB  - A variety of clinical, epidemiological, and experimental data suggest that
      rheumatic heart disease and autoimmune myocarditis are not only similar in their
      pathogenesis, but may often be due to combined infections with coxsackie virus
      (CX) and streptococcus A bacteria (SA). This paper reviews the evidence for this
      hypothesis, provides some new experimental data supporting the hypothesis, and
      suggests specific experiments for testing it. While, it is well-established that
      the M protein of SA mimics myosin, we demonstrate using homology search tools
      that various CX proteins mimic actin. We further demonstrate that antibody
      against CX recognizes actin as an antigen, and that anti-actin antibodies
      recognize CX antigen. Thus, anti-CX antibodies may also target muscle. Moreover,
      since myosin and actin are molecularly complementary, it follows that some SA and
      CX proteins may be molecularly complementary. Some antibodies against these
      complementary proteins in SA and CX should therefore act like idiotype
      antiidiotype antibodies. We show that, indeed, CX and SA antibodies precipitate
      each other. Thus, it is possible that combined CX-SA infections produce more
      severe disease by producing pairs of idiotypic antibodies that act like
      antiidiotypic antibodies as well, thereby, disregulating immune control and
      triggering an autoimmune reaction against both myosin and actin simultaneously.
      We predict that combinations of the appropriate actin- and myosin-like antigens
      from CX and SA will, therefore, be much more autoimmunogenic than antigens from
      CX or SA alone, and that the combination will not require use of adjuvants or
      self-proteins that many current protocols require. It is possible that co
      infections involving CX or SA with other infectious agents may produce similarly
      enhanced disease.

PMID- 18608178
TI  - Cell surface and relative mRNA expression of heat shock protein 70 in human
      synovial cells.
AB  - Heat shock proteins (Hsps) have been repeatedly implicated to participate in the
      pathogenesis of rheumatoid arthritis (RA). METHODS: Herein, Hsp70 cell surface
      and mRNA expression were studied in human fibroblast-like synovial cells, dermal
      fibroblasts and peripheral blood leukocytes derived from 24 RA patients, who
      underwent synovectomy by using flow-cytometric analysis and real-time
      quantitative reverse-transcriptase polymerase chain reaction. For comparison,
      peripheral blood leukocytes of 17 healthy controls were tested. RESULTS:
      Significantly higher Hsp70 membrane positivity was found on fibroblast-like
      synovial cells in RA patients (average 18.3%, median 16.5%) than on autologous
      and healthy control peripheral blood lymphocytes (RA patients: average 4.7%,
      median 2.9%, p = 0.002; healthy controls: average 6.0%, median 4.5%, p = 0.002)
      and/or autologous dermal fibroblasts (average 5.1%, median 4.3%, p < 0.001).
      Strong Hsp70 cell surface expression was also found on peripheral blood monocytes
      of RA patients (average 53.0%, median 58.1%) and healthy controls (average 49.4%,
      median 47.5%, p = 0.52). Peripheral blood granulocytes of healthy controls
      (average 41.8%, median 41.4%) showed significantly increased Hsp70 expression
      comparing with RA patients (average 10.7%, median 6.4%, p = 0.005). Significantly
      higher Hsp70 gene expression was observed in synovial cells of RA patients
      (average 2.04, median 1.7) when compared with autologous peripheral blood
      leukocytes (average 0.75, median 0.68; p < 0.001). However, the difference in
      Hsp70 gene expression between RA-derived synovial cells and healthy control
      peripheral blood leukocytes (average 1.69, median 1.64) was not observed (p =
      0.83). We also found significantly lower relative gene expression in peripheral
      blood leukocytes of RA patients in comparison with healthy controls (p < 0.001).
      Interestingly, we found that Hsp70 gene expression in RA non-affected skin dermis
      gained from the operation wound was 3.7-fold higher in average (average 7.6,
      median 8.3) when compared to autologous RA-affected synovial tissue (p < 0.001);
      10.1-fold higher in average when compared to autologous peripheral blood
      leukocytes (p < 0.001) and 4.5-fold higher in average comparing to control
      peripheral blood leukocytes (p < 0.001). CONCLUSION: Hsp70 gene expression in RA
      affected synovial tissue is followed by Hsp70 cell surface expression on
      fibroblast-like synovial cells growing from RA synovial tissue. Hsp70 may be
      translocated to the cell surface from the cytosol and/or Hsp70 released from
      inflamed synovial tissue may be captured onto the membrane of synovial cells from
      the extracellular space via Hsp receptors. As a physiological response to
      potentially harmful enviromental stress factors, skin dermis produces higher
      levels of Hsp70 comparing to the cells of internal organs and tissues.

PMID- 18608179
TI  - Cross-reactive myelin antibody induces renal pathology.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an autoimmune model for
      multiple sclerosis (MS). Previously, we reported renal immunoglobulin (Ig)
      deposition in mice with myelin oligodendrocyte glycoprotein (MOG(92-106))-induced
      progressive EAE and naive mice injected with MOG(92-106) hybridoma cells
      producing antibody that cross-reacts with various autoantigens including double
      stranded DNA. To assess whether MOG(92-106) antibodies actually induce kidney
      changes, the extent of renal Ig deposition and changes in glomerular histology
      and filtration were investigated. Mice with progressive EAE exhibited Ig
      deposition, glomerular hypercellularity and proteinuria indicating kidney
      dysfunction. MOG(92-106) hybridoma cell injected mice also had Ig deposition and
      proteinuria. Therefore, sensitization with MOG(92-106) and transfer of MOG(92
      106) antibodies can induce both central nervous system and renal pathology. The
      renal involvement reported in MS is believed to occur as a side effect of
      nephrotoxic drugs or neurogenic bladder. Our results demonstrate that an
      autoimmune response against myelin could induce pathologic changes in the kidney
      and may help explain renal changes reported in patients with progressive MS.

PMID- 18608184
TI  - The relationship between subclinical atherosclerosis and electrocardiographic
      abnormalities as biomarkers of cardiovascular risk.
AB  - Electrocardiographic findings indicating myocardial disease, such as left
      ventricular hypertrophy or ST-T wave abnormalities, or the presence of coronary
      artery calcium, indicating atherosclerotic coronary artery disease, are both
      biomarkers of future cardiovascular (CV) risk. Although the risk factors for
      myocardial and coronary artery disease are similar, their concomitant expression
      has implications for CV disease screening and prevention programmes. The
      relationship between the resting 12-lead ECG and subclinical atherosclerosis
      measured as coronary artery calcium (CAC) with electron beam tomography was
      examined in 937 healthy participants (aged 40-50 years) enrolled in a CV risk
      screening study. Electrocardiograms and CAC were interpreted in blinded fashion,
      using standard criteria. An abnormal ECG was coded in 268 (28.6%) participants,
      most commonly left ventricular hypertrophy (3.1%), delayed precordial R wave
      transition (5.7%), T-wave abnormalities (10.0%) and intraventricular conduction
      delay (10.4%). Although abnormal ECG findings were associated with CV risk
      variables, the prevalence of any CAC was similar in subjects with any ECG finding
      (43 of 268, 16.0%) compared with those with normal ECGs (125 of 669, 18.7%, p
      =NS). In a logistic model controlling for CV risk factors including systolic
      blood pressure, low-density lipoprotein cholesterol (LDL-C), body mass index
      (BMI), glycosylated haemoglobin, race, age and gender, significant associations
      with CAC were found for LDL-C, race and BMI. There was no significant
      relationship between CAC and ECG abnormalities (odds ratio 0.80, 95% confidence
      interval 0.54-1.20). In conclusion, electrocardiographic abnormalities and
      subclinical calcified atherosclerosis were not significantly associated with each
      other in this middle-aged screening population. This suggests these two
      biomarkers may be complementary towards broader detection of latent CV risk.

PMID- 18608185
TI  - Effect of aberrant promoter methylation of FHIT and RASSF1A genes on
      susceptibility to cervical cancer in a North Indian population.
AB  - As current evidence suggests the involvement of epigenetic modification of tumour
      suppressor genes in human cancer, we investigated the aberrant promoter
      methylation of FHIT and RASSF1A genes in human papillomavirus (HPV)-mediated
      cervical cancer in Indian women. We analysed 60 cervical cancer tissue biopsies
      of different clinical stage and histological grading and 23 healthy control
      samples with normal cervical cytology. Methylation-specific polymerase chain
      reaction (MSP) was performed to analyse the methylation status of FHIT and
      RASSF1A genes and confirmed by sequencing. Both patients and controls were
      screened for HPV infection and 98% of the HPV-infected cases showed positivity
      for HPV type 16. Aberrant promoter methylation of the FHIT gene was found in
      28.3% (17/60) of cases and of the RASSF1A gene in 35.0% (21/60) of cases;
      promoter methylation of both the genes was found in 13.3% (8/60) of cervical
      cancer cases. Methylation was significantly (p<0.01) associated with the cervical
      cancer cases compared with controls. None of the 23 controls was found to be
      methylated in either of these genes. This is the first study indicating a
      correlation between the promoter methylation of FHIT and RASSF1A genes and the
      clinical stage and histological grading of cervical carcinoma in Indian women.
      Future studies are underway to examine the practical implications of these
      findings for use as a biomarker.

PMID- 18608187
TI  - An integrated approach to biomonitoring exposure to styrene and styrene-(7,8)
      oxide using a repeated measurements sampling design.
AB  - The aim of this work was to investigate urinary analytes and haemoglobin and
      albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene
      (7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic
      polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers. We
      obtained three or four air and urine samples from each exposed worker (eight
      reinforced plastics workers and 13 varnish workers), one air and urine samples
      from 22 control workers (automobile mechanics) and one blood sample from all
      subjects. Median levels of exposure to Sty and StyOX, respectively, were 18.2 mg
      m(-3) and 133 microg m(-3) for reinforced plastics workers, 3.4 mg m(-3) and 12
      microg m(-3) for varnish workers, and <0.3 mg m(-3) and <5 microg m(-3) for
      controls. Urinary levels of styrene, mandelic acid, phenylglyoxylic acid,
      phenylglycine (PHG), 4-vinylphenol (VP) and mercapturic acids (M1+M2), as well as
      cysteinyl adducts of serum albumin (but not those of haemoglobin) were
      significantly associated with exposure status (controls<exposed workers). Also,
      levels of VP and M1+M2 were significantly affected by smoking, and levels of
      M1+M2 were significantly affected by GSTM1 polymorphisms. Multiple linear
      regression analyses of the subject-specific (logged) metabolite levels across
      exposed workers showed that Sty was a significant predictor for all urinary
      analytes while StyOX was a significant predictor of PHG only. Interestingly, the
      log scale regression coefficients for Sty in these models were significantly less
      than one for all metabolites except M1+M2. This suggests that the natural scale
      relationships between levels of all Sty metabolites, except M1+M2, displayed
      downward concavity with increasing Sty exposure, suggestive of saturable
      metabolism. Levels of the protein adducts were not associated with exposure to
      either Sty or StyOX among exposed subjects.

PMID- 18608194
TI  - Association of aortic pressures with fasting plasma glucose in patients with and
      without impaired fasting glucose.
AB  - BACKGROUND: Diabetes mellitus and impaired fasting glucose (IFG) are associated
      with future cardiovascular disorders. Aortic pulse pressure (PP) and fractional
      pulse pressures (FPPs) are strong and independent indicators of the risk of
      coronary heart disease. These conditions have been reported to be associated with
      endothelial dysfunction. In the present study, aortic PP and FPPs of patients
      with and without impaired fasting glucose were evaluated. METHODS: Fifty patients
      with IFG with a mean age of 56.8+/-12.2 years and 47 patients with normal fasting
      glucose (NFG) with a mean age of 53.1+/-11.2 years were included in the study.
      All subjects had angiographically proven normal coronary arteries without
      coronary slow flow. Aortic systolic and diastolic blood pressures were measured
      invasively. Mean pressure, PP and FPPs (aortic PP/mean pressure) were calculated.
      RESULTS: All parameters measured were significantly higher in the IFG group than
      in the control (NFG) group (133+/-21 mmHg and 117+/-12 mmHg, p<0.001 for aortic
      systolic pressure; 79+/-12 mmHg and 74+/-8 mmHg, p = 0.035 for aortic diastolic
      pressure; 97+/-14 mmHg and 88+/-9 mmHg, p = 0.001 for aortic mean pressure; 54+/
      13 mmHg and 43+/-8 mmHg, p<0.001 for aortic PP; 0.56+/-0.10 and 0.48+/-0.08,
      p<0.001 for aortic FPP). In addition, in linear regression analysis, a positive
      correlation was found between fasting plasma glucose and the aortic FPP (p =
      0.001, R2 = 0.12). CONCLUSION: Ascending aorta PP and FPPs are significantly
      associated with the presence of IFG. These findings suggest that IFG is
      associated with endothelial dysfunction and so aortic stiffness.

PMID- 18608196
TI  - Left ventricular apical rotation is related to ambulatory blood pressure and body
      mass in healthy elderly females.
AB  - OBJECTIVE: The interaction between left ventricular (LV) apical rotation, blood
      pressure (BP) and body mass in elderly females may reveal mechanisms involved in
      the syndrome of diastolic heart failure. METHODS: Thirty-one healthy females, age
      69-84 years, were studied with echocardiography, ambulatory BP and an exercise
      capacity (VO2peak) test. RESULTS: LV apical short-axis loops were eligible for
      speckle tracking analysis in 27 subjects. Peak apical rotation (PAR) correlated
      inversely with diastolic BP (r = -0.47, p = 0.01). PAR correlated positively with
      stroke volume and body weight (p<0.05), but not with VO2peak (n = 19, p = ns).
      PAR also correlated with peak rotation velocity in systole (r = 0.76, p<0.0001)
      and in diastole (r = 0.58, p = 0.001). Diastolic peak rotation velocity
      correlated with mitral E wave peak velocity (r = 0.48, p = 0.01). There was a
      significant reduction in LV volumes during the 4 years of follow-up. CONCLUSIONS:
      In healthy elderly females, there seems to be an interaction between LV apical
      rotation, BP and body mass. Peak apical rotation and peak diastolic rotation
      velocity correlate with indices of LV filling and ejection, indicating that
      suction, a crucial element for effective early LV filling, may be preserved in
      healthy elderly subjects. Suction deteriorates with elevations of the arterial
      BP. An age- and BP-related reduction in LV end-diastolic volume may represent an
      additional impediment to LV filling. Both features may contribute to the
      development of LV diastolic dysfunction and to episodes of diastolic heart
      failure.

PMID- 18608197
TI  - Effects on plasma noradrenaline may explain some of the improved insulin
      sensitivity seen by AT-1 receptor blockade.
AB  - AIMS: We have previously found improved insulin sensitivity in hypertensives
      after additional treatment with angiotensin II-receptor blocker (ARB) compared
      with calcium-channel blocker (CCB) alone, despite similar blood pressure lowering
      effects. In this study, we compare the effect of these two principal different
      vasodilating agents on the autonomic nervous system in the same patients, and
      test whether potential differences in these variables might explain the
      difference seen in insulin sensitivity. METHODS: In a double-blind crossover
      study, 21 hypertensive patients were randomized to receive either 100 mg losartan
      (ARB) or 5 mg amlodipine (CCB) in addition to an open-labelled treatment of
      amlodipine 5 mg. The patients were treated for 8 weeks with either treatment
      regimens after a 4-week run-in and a 4-week washout period. Plasma catecholamines
      were measured using radioenzymatic technique and baroreflex sensitivity and heart
      rate variability was tested at rest and during 24-h ECG registration. RESULTS:
      Plasma noradrenaline was significantly lower after additional treatment with ARB
      compared with CCB alone (304+/-29 pg/ml vs 373+/-43 pg/ml, p = 0.022). Heart rate
      variability, baroreflex sensitivity or plasma adrenaline did not differ
      significantly between the two treatment regimens. CONCLUSION: The results may
      suggest that improvement of insulin sensitivity by ARB is related to decreased
      plasma noradrenaline and potential sympatholytic effects.

PMID- 18608198
TI  - Heightened acute circulatory responses to smoking in women.
AB  - Objective. Smoking, a major risk factor for cardiovascular morbidity and
      mortality, may be particularly harmful to women. Sympathetic and hemodynamic
      responses to cigarette smoking may be implicated in the link between smoking and
      acute cardiovascular events. We tested the hypothesis that acute effects of
      smoking on cardiovascular function are potentiated in women compared with men.
      Methods. We examined the effects of cigarette smoking and sham smoking on muscle
      sympathetic nerve activity, blood pressure and heart rate in 20 female and 20
      male middle-aged healthy habitual smokers. Results. Sham smoking had no effect on
      muscle sympathetic nerve activity, blood pressure, or heart rate. Although
      cigarette smoking increased average systolic blood pressure and heart rate in
      both females and males, systolic blood pressure increased more in women (12+/-2
      mmHg) than in men (6+/-2 mmHg; p = 0.02), as did heart rate (16+/-2 beats/min in
      women vs 9+/-2 beats/min in men; p = 0.002). Female smokers also had greater
      smoking-related increases in systolic blood pressure variability compared with
      males (2.2+/-0.6 vs 0.4+/-0.4 mmHg, respectively; p = 0.01) and greater decreases
      in RR variability (-28+/-5 vs -7+/-4 ms; p = 0.002). Despite the potentiated
      blood pressure increase in females, which would be expected to inhibit
      sympathetic activity to a greater extent in females than in males, changes in
      muscle sympathetic nerve activity during smoking were similar in both sexes.
      Conclusions. Acute pressor and tachycardic effects of smoking are potentiated in
      women compared with men. These findings may have important implications for
      understanding increased vulnerability to acute cardiovascular events in women who
      smoke.

PMID- 18608199
TI  - The clinical significance of abnormal diurnal blood pressure variation in healthy
      late middle-aged and older adults.
AB  - Objective. A fall in nocturnal blood pressure (BP) is generally observed in
      normotensive subjects as well as in those with mild to moderate essential
      hypertension, regardless of the level of daytime BP. Among elderly hypertensive
      subjects, extreme-dippers with a marked nocturnal fall in BP as well as non
      dippers with nocturnal fall absence are at increased risk for cardiovascular and
      cerebrovascular complications. However, the relationship between these abnormal
      diurnal BP variation patterns in normotensive elderly subjects has not been
      investigated. Methods. We classified 45 healthy late middle-aged and older adults
      into three groups according to the nocturnal systolic BP fall pattern examined by
      24-h ambulatory BP monitoring (dipper, non-dipper and extreme-dipper), and
      compared the parameters of initial atherosclerosis, endothelial function and
      autonomic function. As a parameter of atherosclerotic factors, the intima-media
      thickness (IMT) of the carotid artery was examined, and as a parameter of
      endothelial function, brachial artery endothelium-dependent flow-mediated
      dilation (FMD) was ultrasonographyically measured. Autonomic function was
      assessed by power spectral analysis of heart rate variability (HRV). Results. No
      difference was observed in the severity of IMT between the three groups. The
      percent change of FMD in subjects in the extreme-dipper group was significantly
      lower than that of subjects in the dipper group, indicating that extreme-dippers
      in healthy elderly subjects may be associated with endothelial dysfunction. Also,
      HRV due to sympathetic modulation of subjects in the extreme-dipper group was
      significantly higher than that of subjects in the dipper and non-dipper groups,
      suggesting the activation of sympathetic tone. Conclusion. In healthy elderly
      subjects, the extreme-dipper type may reflect a decrease in endothelial function,
      i.e. initial stage atherosclerosis, rather than the dipper type.

PMID- 18608200
TI  - Progressive effects of valsartan compared with amlodipine in prevention of
      diabetes according to categories of diabetogenic risk in hypertensive patients:
      the VALUE trial.
AB  - We have previously shown that the angiotensin receptor blocker valsartan is
      associated with a lower incidence of new-onset type 2 diabetes than that with the
      calcium-channel antagonist amlodipine in the treatment of hypertensive patients
      at high cardiovascular risk. We have now investigated the benefits of valsartan
      vs amlodipine in patients of different categories of diabetogenic risk. Some 9995
      patients without diabetes at onset participated in VALUE, with average follow-up
      of 4.2 years. Predictors of new diabetes were analyzed by stepwise logistic
      regression. A diabetes risk score for each patient was calculated based on a
      multivariate model. The risk of developing new diabetes in quartiles of risk for
      the disease was calculated as an odds ratio (OR) with 95% confidence intervals
      (CI). New diabetes was reported in 580 (11.5%) patients on valsartan and in 718
      (14.5%) patients on amlodipine (p<0.0001). There was a more than sevenfold rise
      in the development of new diabetes from the lowest to the highest quartile of
      risk. When study treatment was included in the risk model, the odds in favor of
      valsartan in preventing new diabetes progressively increased with higher risk.
      Fifty-two (4.03%) patients developed diabetes on valsartan and 50 (4.14%)
      patients on amlodipine in the lowest quartile of risk, 73 (5.70%) patients on
      valsartan and 83 (6.81%) patients on amlodipine in the second quartile, and 126
      (10.27%) patients on valsartan and 160 (12.58%) patients on amlodipine in the
      third quartile. The difference between treatments was highly significant in
      quartile 4 with 329 (26.68%) patients developing new diabetes on valsartan vs 425
      (33.57%) patients on amlodipine (OR = 0.72, 95% CI 0.61-0.86, p = 0.0002). The
      number of patients needed for treatment for the duration of the trial in order to
      gain the benefit of valsartan over amlodipine in preventing one new case of
      diabetes was 43 in the third quartile and 15 in the fourth quartile of risk
      categories. We conclude that valsartan compared with amlodipine reduces the risk
      of developing diabetes mellitus, particularly in hypertensive patients with the
      highest susceptibility for development of diabetes.

PMID- 18608201
TI  - Parent perceptions of school-based support for students with traumatic brain
      injuries.
AB  - PRIMARY OBJECTIVE: To determine whether parents believe schools provided
      necessary support to their children who sustained traumatic brain injuries.
      RESEARCH DESIGN: Interview, to determine parent perceptions. METHODS AND
      PROCEDURE: Sixty-six primary caregivers of school-age children who experienced a
      TBI within the previous 2 years were interviewed regarding what types of special
      support were needed by and provided for their children during the 3 months
      immediately following school re-entry. They then rated how difficult it was to
      obtain support or services from the school and how satisfied they were with the
      support or services. MAIN OUTCOMES AND RESULTS: The majority of participants did
      not perceive the need for school-based services, even when the injury was severe.
      Almost all students whose parents perceived a need for an adjusted schedule were
      granted that accommodation, but few students received school-based counselling or
      behavioural support. CONCLUSIONS: Results indicated that participants perceived
      relatively few school-based supports, particularly given the actual academic,
      behavioural and social challenges experienced by children who have sustained a
      TBI. Schools and hospitals must take steps to ensure appropriate post-head injury
      support services.

PMID- 18608202
TI  - Using a temporal discounting paradigm to measure decision-making and impulsivity
      following traumatic brain injury: a pilot study.
AB  - PRIMARY OBJECTIVE: This study reports on a pilot study using a temporal
      discounting paradigm and a standardized impulsivity questionnaire to examine
      decision-making in a group of brain injured patients and age matched controls.
      METHODS AND PROCEDURES: Participants were asked to choose between a larger reward
      available at a specified time in the future and smaller reward available
      immediately. OUTCOME AND RESULTS: Each of the two groups demonstrated temporal
      discounting; that is, the subjective value of the reward decreased with
      increasing delay. However, the TBI group discounted more than the controls,
      suggesting that their decision-making was more impulsive. CONCLUSION: The results
      suggest that a temporal discounting paradigm might be a useful method of
      assessing decision-making after head trauma, especially in cases where capacity
      to make decisions about financial awards is an issue or in respect of money
      management generally.

PMID- 18608203
TI  - Attributions for behaviours of persons with brain injury: the role of perceived
      severity and time since injury.
AB  - PRIMARY OBJECTIVE: The experiment determined first whether visible markers of
      brain injury shape judgements of severity of injury and time since injury; and
      secondly whether these two judgements predict attributions for undesirable
      actions performed by an adolescent with brain-injury. RESEARCH DESIGN: Scenarios
      presented a photograph of an adolescent, in one condition with a head scar and in
      a second condition with no scar. The adolescent was described as having suffered
      a brain injury and showing four behaviour changes, concerning sleep, anger, self
      confidence and motivation. METHODS AND PROCEDURES: For each behaviour, students
      (n = 101) rated attributions to the brain injury and adolescence and estimated
      severity of injury and time since injury. OUTCOMES AND RESULTS: With no scar,
      participants attributed the behaviours to adolescence more than brain injury,
      whereas with the scar they invoked both causes equally. With the scar they rated
      severity higher and time since injury shorter; severity predicted participants'
      attributions for the behaviours. CONCLUSIONS: Visible markers of injury such as
      scars are spurious indicators of severity but they shape judgements of severity
      and attributions for actions of persons with brain injury. These results inform
      more accurate diagnosis and treatment for actions resulting from brain injury.

PMID- 18608204
TI  - Prefrontal cortex involvement in the event-based prospective memory: evidence
      from patients with lesions in the prefrontal cortex.
AB  - PRIMARY OBJECTIVE: The aim of the present study was to investigate the event
      based prospective memory (EBPM) and time-based prospective memory (TBPM) in
      patients with lesion in prefrontal cortex (PFC) and test the hypothesis that the
      prefrontal cortex is involved in the prospective memory (PM) network. RESEARCH
      DESIGN: The performance of patients with lesion in PFC (n = 30) was compared with
      that of a demographically matched control group (n = 30). METHODS AND PROCEDURES:
      A neuropsychological battery of tests including EBPM and TBPM tasks were
      administered to both groups. MAIN OUTCOME AND RESULTS: The group with lesion in
      PFC were significantly impaired in EBPM, but insignificantly impaired in TBPM
      tasks. There was no difference in performance of EBPM and TBPM tasks between the
      patients with lesion in the left and the right PFC. CONCLUSIONS: These results
      suggest that the patients with lesion in PFC were impaired in EBPM, but not in
      TBPM, implying that EBPM and TBPM may have different neural substrates. It is
      possible that PFC is more selectively involved in EBPM, but less in TBPM.

PMID- 18608205
TI  - Combination treatment of human umbilical cord matrix stem cell-based interferon
      beta gene therapy and 5-fluorouracil significantly reduces growth of metastatic
      human breast cancer in SCID mouse lungs.
AB  - Umbilical cord matrix stem (UCMS) cells that were engineered to express
      interferon-beta (IFN-beta) were transplanted weekly for three weeks into MDA 231
      breast cancer xenografts bearing SCID mice in combination with 5-fluorouracil (5
      FU). The UCMS cells were found within lung tumors but not in other tissues.
      Although both treatments significantly reduced MDA 231 tumor area in the SCID
      mouse lungs, the combined treatment resulted in a greater reduction in tumor area
      than by either treatment used alone. These results indicate that a combination
      treatment of UCMS-IFN-beta cells and 5-FU is a potentially effective therapeutic
      procedure for breast cancer.

PMID- 18608206
TI  - TLR4 signaling induces B7-H1 expression through MAPK pathways in bladder cancer
      cells.
AB  - TLR4 (Toll-like receptor 4) and B7-H1, which were known to be restricted to
      immune cells in the past, were found to be aberrantly expressed in a majority of
      tumor cells, facilitating tumor evasion from immune surveillance. Our study
      demonstrated that activation of TLR4 signaling in bladder cancer cells up
      regulated B7-H1 expression. Furthermore, this regulation was significantly
      attenuated by ERK or JNK inhibitor. Our results elucidated the molecule mechanism
      of regulation of B7-H1 expression through TLR4 signaling and may suggest new
      strategies of down-regulating the cancer-associated B7-H1 expression for bladder
      cancer treatment.

PMID- 18608207
TI  - Whole body radiography for bone survey screening of cancer and myeloma patients.
AB  - PURPOSE: To determine the utility of a rapid, low dose whole body radiographic
      system (Statscan) for the detection of focal metastatic deposits in cancer
      patients and multifocal disease in myeloma patients. MATERIALS AND METHODS: After
      IRB approval, 30 consecutive patients had a frontal and lateral whole body
      radiography done with the Statscan system as a substitute for conventional
      radiographic skeletal survey. Both whole body images were obtained in less than
      five minutes. Images were retrospectively reviewed, independently, by three
      musculoskeletal radiologists. Findings were compared to information from all
      other available imaging studies. Final determinations were by consensus. RESULTS:
      Of the 30 patients in the study group, there were 18 men and 12 women with an age
      range from 37 to 88 years, average 60 years. Diagnoses were MGUS/multiple myeloma
      in 18 cases, lymphoma/leukemia in two cases, and cancer in 11 cases. Eleven of
      the Statscan exams were interpreted by all three radiologists as normal. The
      remaining 19 Statscan exams showed a total of 117 lesions (96 osteolytic and 21
      osteoblastic). Ninety percent of these (106/117) were confirmed as areas of
      suspected metastatic disease or multifocal involvement by a variety of other
      imaging studies (radiographic bone survey-7, CT-33, MR-13, bone scan-4, PET/CT
      8). CONCLUSION: The Statscan whole body radiographic system is a useful method
      for detecting focal metastatic disease in cancer patients and multifocal
      involvement in myeloma patients.

PMID- 18608208
TI  - Statin-induced inhibition of MCF-7 breast cancer cell proliferation is related to
      cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced
      oxidative stress.
AB  - Statins have antiproliferative and anti-tumoral effects in MCF-7 cells. We
      determined the effect of statins upon MCF-7 cell cycle, toxicity, cell death,
      reactive oxygen species (ROS) production and mitochondrial membrane potential.
      Fluvastatin, simvastatin and atorvastatin inhibited cell proliferation.
      Antiproliferation was associated with a decrease in the DNA synthesis and a cell
      cycle arrest in the G1 and G2/M phases. A loss in the mitochondrial membrane
      potential was observed with fluvastatin. Statins induced increase in ROS
      production that was associated with cell death, which was abrogated by the
      antioxidant NAC. Our results suggest that the cytotoxic effect observed is
      mediated by an oxidative stress.

PMID- 18608209
TI  - Bladder cancer initiating cells (BCICs) are among EMA-CD44v6+ subset: novel
      methods for isolating undetermined cancer stem (initiating) cells.
AB  - Bladder cancer stem (initiating) cell has not been isolated now, and no one
      verified its persistence experimentally. The aim of this study was to conclude
      the persistence of bladder cancer stem (initiating) cell in human primary bladder
      cancer and investigate the possibility of EMA(-) CD44v6(+) as markers of bladder
      cancer stem (initiating) cell. Genes differentially expressed between normal
      urothelium and low malignant bladder cancer were identified by DNA array assay.
      Overpressed stem cell related genes, Bmi-1 and EZH2, were verified by
      immunohistochemistry. Side population cells in bladder cancer were found under
      fluorescence microscope. The value of 28 potential surface markers of bladder
      cancer stem (initiating) cell for isolating them were judged by
      immunohistochemistry. Both EMA(-) and CD44v6(+) cells located in basal layer
      (potential location of stem cells). After gathering the CD44v6(+) cells and EMA(
      ) cells by magnetic cell sorting, their ability for colony-forming, self-renewal
      and extensive proliferation were assayed by cells culture. Both EMA(-) cells and
      CD44v6(+) cells posses the ability for colony-forming, self-renewal and
      proliferation. We conclude the persistence of bladder cancer stem (initiating)
      cell. Bladder cancer stem (initiating) cell might be among EMA(-) CD44v6(+)
      subset. Our strategies for isolating bladder cancer stem (initiating) cell might
      be useful for isolating other undetermined epithelial cancer stem cell,
      especially those in well-differentiated cancers.

PMID- 18608210
TI  - 5-Aza-2'-deoxycytidine restores proapoptotic function of p53 in cancer cells
      resistant to p53-induced apoptosis.
AB  - The expression of p53-target genes encoding the proapoptotic factor Noxa, but not
      PUMA, was not induced by p53 in HCT116 and SW480 cells, which show resistance to
      apoptosis in response to p53 overexpression. The lack of p53 inducibility of Noxa
      was restored by treatment with the DNA methyltransferase inhibitor 5-Aza-2'
      deoxycytidine (5-aza-CdR). Furthermore, p53 induced apoptosis in HCT116 and SW480
      cells treated with 5-aza-CdR. Moreover, the inhibition of Noxa expression by RNAi
      in 5-aza-CdR-treated HCT116 cells resulted in the partial inhibition of p53
      induced apoptosis. These results suggest that epigenetic cancer therapy is
      possible for some cancers in combination with forced p53 activation.

PMID- 18608211
TI  - The effect of dalteparin, a kind of low molecular weight heparin, on lung
      adenocarcinoma A549 cell line in vitro.
AB  - The beneficial effects of unfractionated heparin and low molecular weight heparin
      on cancer progression have been reported. In the study, the effect of dalteparin
      on pulmonary adenocarcinoma A549 cell line was observed in vitro. Our experiments
      revealed that: (1) dalteparin can inhibit the cell viability dose-dependently and
      time-dependently; (2) dalteparin can arrest the A549 cells in G(1) phase and
      induce them to early apoptosis; (3) dalteparin exerts its effects through
      p21(WAF1) and p27(KIP1) proteins; and (4) the changes of p21(WAF1) and p27(KIP1)
      proteins caused by dalteparin occurred at posttranscriptional levels.

PMID- 18608212
TI  - Current status and issues in cancer stem cell study.
AB  - Cancer stem cells (CSCs) have been positively identified and successfully
      isolated from some but not all cancers. The studies on CSCs to date suggest that
      these cells are rare among the tumor cell population, and they are capable of
      self-renewing and maintaining tumor growth and heterogeneity. Therapies aimed at
      CSCs have shown some promise, but their further development will require a more
      thorough understanding of the biology of CSCs and methods for identifying and
      isolating this cell subpopulation. This review examines what is known to date
      regarding the similarities and differences between cancer and somatic stem cells:
      CSC surface marker development and cell isolation (including a model isolation
      from our lab), the frequency, potential origin, and signal transduction of CSCs,
      and the current state of CSC-targeting therapeutic strategies.

PMID- 18608213
TI  - Herbal isoprenols induce apoptosis in human colon cancer cells through
      transcriptional activation of PPARgamma.
AB  - Farnesol (FOH) and geranylgeraniol (GGOH) possess anti-tumor potential, while
      peroxisome proliferator-activated receptor gamma (PPARgamma) has exhibited
      modulating effects in colorectal cancers. We investigated the anti-carcinogenic
      effects of these isoprenols in HT-29 and HCT116 colon cancer cells and PPARgamma
      involvement. Results indicate that the FOH- and GGOH-induced apoptosis involve
      caspase 3 activation, PARP cleavage, nuclear chromatin condensation, down
      regulation of Bcl-x(L) and survivin expression, with increased PPARgamma promoter
      activity. Pretreatment of the PPARgamma antagonist GW9662 reduces FOH-induced
      growth inhibition and the associated PARP cleavage. We conclude that PPARgamma
      activation is essential to elicit the anti-carcinogenic action of herbal
      isoprenols in colonic cancer cells.

PMID- 18608214
TI  - Inhibition of CD147 gene expression via RNA interference reduces tumor cell
      proliferation, activation, adhesion, and migration activity in the human Jurkat T
      lymphoma cell line.
AB  - CD147, a leukocyte surface molecule over-expressed in T-lymphoma cells, is
      reportedly associated with lymphocyte activation and proteinase production via
      interactions with fibroblasts and plays a role in stromal invasion by lymphoma
      cells. To determine the role of CD147 in the progression of T-lymphoma, we
      performed siRNA interference-mediated knockdown of CD147 in a CD147-expressing
      Jurkat T-cell line. CD147 knockdown resulted in the decreased proliferation and
      migration of Jurkat cells and reduced the adhesion of Jurkat cells to
      extracelluar matrix fibronectin in vitro. CD147-siRNA inhibited the activation of
      Jurkat cells via down-regulation of CD25 expression. Our results indicate that
      CD147 is involved in T-lymphoma progression, a finding useful in efforts to
      develop targeted therapies to treat patients with T-lymphoma.

PMID- 18608215
TI  - Lower level of MAPK expression is associated with anthracycline resistance and
      decreased survival in patients with hormone receptor negative breast cancer.
AB  - INTRODUCTION: Hormone receptor negative breast cancer is encountered in about 30%
      of all patients with breast cancer and is considered as a prognostically
      unfavorable subset. The aim of this study is to evaluate the prognostic impact of
      various molecular markers in patients with receptor negative breast cancer.
      METHODS: Tumor specimens from 140 patients with receptor negative (ER, PR) breast
      cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by
      immunohistochemistry. The prognostic significance of these molecular factors, in
      addition to various prognostic variables were determined with respect to disease
      free and overall survival. RESULTS: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and
      47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK,
      respectively. Twenty-three patients with positive MAPK (16.4%) had a high level
      of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower
      percentage of MAPK expression was significantly associated with a poorer OS (p =
      0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for
      MAPK. Anthracycline resistance remained the only independent significant variable
      for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with
      recurrent disease, median survival after initial relapse was 16.8 months. MAPK
      was determined as the only prognostic factor for this endpoint. Patients with
      higher level of MAPK staining showed significantly shorter survival following
      initial recurrence (p = 0.04). CONCLUSION: MAPK expression is a significant
      prognostic factor for non-metastatic patients with hormone receptor breast
      cancer. A lower level of staining is shown to be associated with with
      antracycline resistance and oveall survival, whereas a higher expression level is
      correlated with shorter survival following initial relapse, suggesting possible
      role of different molecular mechanisms pertaining to tumor progression once
      recurrence occurs. Further translational research is required to elucidate
      molecular mechanisms of the cross-talk between intracellular signaling and
      molecular pathways leading to drug resistance in patients with receptor negative
      breast cancer.

PMID- 18608216
TI  - Annexin A2 regulates the levels of plasmin, S100A10 and Fascin in L5178Y cells.
AB  - Annexin A2 (ANXA2) was reported as the receptor, activator, expression enhancer,
      or cooperator for plasmin, S100A10, and others. To delineate the effect of ANXA2
      on the proteins that are probably associated with tumor development and
      metastasis by a credible experimental method, we generated an ANXA2 gene knockout
      tumor cell line, ANXA2(-/-) L5178Y, and compared the expression levels of
      plasmin, S100A10 and fascin in the generated cell line with in wild type of
      L5178Y at mRNA and protein levels. The results showed that the mRNA level of
      plasminogen (PLG) was not substantially changed in cultured ANXA2(-/-) cells, but
      the protein level of plasmin was significantly lower in the cultured ANXA2(-/-)
      cells than in cultured ANXA2(+/+) cells. For S100A10 and fascin, their mRNA and
      protein levels were significantly lower in the cultured ANXA2(-/-) cells than in
      cultured ANXA2(+/+) cells. Results indicate that ANXA2 introduces the generation
      or expression of plasmin, S100A10, and fascin in tumor cells. ANXA2 affects
      PLG/plasmin level by a way post transcription and may be an inducer or enhancer
      to fascin expression at transcription level. By the regulations, ANXA2 enhances
      the development, invasion, and metastasis of tumor. The detailed mechanism for
      the regulations above remains to be further investigated, but our results show
      the potential of ANXA2 as a new target molecule for the strategies of tumor
      biotherapy or tumor gene therapy.

PMID- 18608217
TI  - Distractibility in Attention/Deficit/ Hyperactivity Disorder (ADHD): the virtual
      reality classroom.
AB  - Nineteen boys aged 8 to 14 with a diagnosis of ADHD and 16 age-matched controls
      were compared in a virtual reality (VR) classroom version of a continuous
      performance task (CPT), with a second standard CPT presentation using the same
      projection display dome system. The Virtual Classroom included simulated "real
      world" auditory and visual distracters. Parent ratings of attention,
      hyperactivity, internalizing problems, and adaptive skills on the Behavior
      Assessment System for Children (BASC) Monitor for ADHD confirmed that the ADHD
      children had more problems in these areas than controls. The difference between
      the ADHD group (who performed worse) and the control group approached
      significance (p = .05; adjusted p = .02) in the Virtual Classroom presentation,
      and the classification rate of the Virtual Classroom was better than when the
      standard CPT was used (87.5% versus 68.8%). Children with ADHD were more affected
      by distractions in the VR classroom than those without ADHD. Results are
      discussed in relation to distractibility in ADHD.

PMID- 18608218
TI  - Brief report: manipulation of task difficulty in inhibitory control tasks.
AB  - The present study investigated how task difficulty can be manipulated in
      inhibitory control tasks. Tasks from three widely used task paradigms - a Go/No
      Go task, a Stop-Signal task,and a Flanker task - were manipulated on two
      parameters each (Go/No-Go task: interstimulus interval, prepotency. Stop-signal
      task: stop-signal-delay, prepotency. Flanker task:number of distractors, size of
      target stimulus). Participants were 86 children (age 4-6) from a population-based
      sample. The results showed no significant effects on the Go/No-Go task but both
      main and interaction effects on the Stop-Signal task and the Flanker task.
      Together, these findings indicate that task difficulty can be successfully
      manipulated in inhibitory control tasks. However, the interactive rather than
      additive effects on performance suggest that the level of one parameter only has
      the desired effect under certain conditions. This new information about how to
      manipulate task difficulty is important when adapting tasks for use with children
      of different ages, as well as when designing training programs for improving
      inhibitory control among children with ADHD.

PMID- 18608220
TI  - Gender differences and cognitive correlates of mathematical skills in school-aged
      children.
AB  - Published information concerning the influence of gender on mathematical ability
      tests has been controversial. The present study examines the performance of
      school-aged boys and girls from two age groups on several mathematical tasks and
      analyzes the predictive value of a verbal fluency test and a spatial test on
      those mathematical tasks. More specifically, our research attempts to answer the
      following two questions: (1) Are gender differences in mathematical test
      performance among children interrelated with age and (2) do verbal and spatial
      nonmathematical tests mediate gender effects on mathematical test performance?
      Two hundred and seventy-eight 7- to 10-year-old children and 248 13- to 16-year
      olds were selected from schools in Colombia and Mexico (231 boys and 295 girls).
      The age effect was found to be significant for all measures, with scores
      improving with age. Results showed that boys and girls in both age groups scored
      similarly in most subtests, but that differences emerged in the performance of
      mental mathematical operations and in resolving arithmetical problems. In the
      latter - but not in mental math - older boys outperformed older girls, whereas no
      gender differences were observed in the younger groups. After controlling for
      age, it was found that the spatial test was, indeed, a significant mediator of
      gender effects, while the verbal task was not.

PMID- 18608219
TI  - Memory functioning in children with reading disabilities and/or attention
      deficit/hyperactivity disorder: a clinical investigation of their working memory
      and long-term memory functioning.
AB  - We examined memory functioning in children with reading disabilities (RD),
      Attention deficit/hyperactivity disorder (ADHD), and RD/ADHD using a clinic
      sample with a clinical instrument: the Children's Memory Scale, enhancing its
      generalizability. Participants included 23 children with RD, 30 with ADHD, 30
      with RD/ADHD, and 30 controls. Children with RD presented with reduced verbal
      short-term memory (STM) but intact visual STM, central executive (CE), and long
      term memory (LTM) functioning. Their deficit in STM appeared specific to tasks
      requiring phonetic coding of material. Children with ADHD displayed intact CE and
      LTM functioning but reduced visual-spatial STM, especially when off stimulant
      medication. Children with RD/ADHD had deficits consistent with both disorders.

PMID- 18608221
TI  - Working memory in individuals with fragile X syndrome.
AB  - The present research tests the hypothesis that fragile X syndrome (FXS) is
      associated with a deficit in working memory (WM) and the deficit is more
      pronounced the higher the control requirements of the task. To this purpose, 15
      boys with FXS and 15 typically developing children, matched for mental age,
      assessed with Logical Operation Test, were tested with batteries of 4 verbal and
      4 visuospatial WM tasks requiring different levels of control. Children with FXS
      showed a performance equal to controls, in WM tasks requiring low and medium-low
      control but significant impairment in correspondence with greater control
      requirements. Results show that boys with FXS present a WM deficit only when high
      control is required by the task, supporting the hypothesis that control can be a
      critical variable distinguishing WM functions and explaining intellectual
      differences. On the contrary the hypothesis that the FXS is associated with a
      visuospatial deficit was not supported.

PMID- 18608222
TI  - A developmental investigation of prospective memory: effects of interruption.
AB  - The effects of interrupting an event-based prospective memory (PM) task and its
      associated ongoing task were compared for two groups of children: 8- to 9-year
      olds (n = 35) and 12- to 13-year-olds (n = 28). Additionally, PM performance was
      examined as a function of attainment on a battery of tests of executive
      functioning (viz., Controlled Oral Word Association Test, Letter Number
      Sequencing Test, Stroop Color and Word Test, and Trail Making Test). A
      significant main effect of age indicated that the older children correctly
      carried out intended actions more often than the younger children. Consistent
      with the prefrontal model of PM, interruption had no impact on PM accuracy in the
      older group but produced reliable decrements to the accuracy of the younger
      group. Whereas IQ showed no association with PM performance, reliable relations
      between PM skills and aspects of their executive functioning were found.

PMID- 18608223
TI  - Parent report of attention problems predicts later adaptive functioning in
      children with brain tumors.
AB  - Children with brain tumors are at risk for psychological and behavioral
      difficulties. This study examined the ability of parent report of attention
      problems, withdrawal, anxiety, and depression, as well as IQ, to predict later
      adaptive functioning in 42 children treated for brain tumors. Age at diagnosis,
      SES, gender, and scores on the Neurological Predictor Scale (NPS) also were
      examined as predictors. Parent report of attention problems, SES, and NPS were
      significant predictors of later adaptive functioning across domains. This finding
      highlights the ability of parent report of attention problems to predict later
      adaptive functioning in children treated for brain tumors.

PMID- 18608224
TI  - Working memory failures in children with arithmetical difficulties.
AB  - A large body of literature has examined the relationship between working memory
      and arithmetic achievement, but results are still ambiguous. To examine this
      relationship, we compared the performance of third and fifth graders with
      arithmetic difficulties (AD) and controls of the same age, grade, and verbal
      intelligence on a battery of working memory tasks, differentiating between
      different aspects of working memory. Children with AD scored significantly lower
      on active working memory tasks requiring manipulation of the to-be-recalled
      information (Listening Completion task, Corsi Span Backwards, Digit Backwards),
      but not in passive working memory tasks, requiring the recall of information in
      the same format in which it had been presented (Digit, Word, and Corsi Forwards
      Span tasks), nor in tasks involving word processing (word articulation rate,
      forwards and backwards word spans). A regression analysis showed that the best
      predictors of differences between AD children and the control group were the
      Corsi Span Backwards, the Listening Completion task, and the rate of articulation
      of pseudowords. The analysis of strategies used by children in mental calculation
      revealed the greater tendency of children with AD to rely on more primitive
      strategies: finger use never appeared as the most frequent strategy in skilled
      children, whereas it was the most used strategy in children with AD. Verbal and
      visual strategies appeared associated with successful performance in third
      graders, but in fifth grade, the most successful strategy was verbalization.

PMID- 18608225
TI  - Developmental changes in attention tests norms: implications for the structure of
      attention.
AB  - Assessment of attention is a key issue in the study of neuropsychological
      development. In this study we collected Hebrew norms for four frequently used
      attention tests (Trail Making, Digit-Symbol, Digit Span, and Digit Cancellation),
      analyzed the developmental sensitivity of each test and traced changes in
      attention across ages. The tests were administered to 809 boys and girls ranging
      in age from 8 to 17, divided into 10 age cohorts. The results indicate that,
      although all tests showed age effects, Digit-Symbol and Digit Cancellation tests
      were most developmentally sensitive. Another interesting finding was that younger
      age groups (8-11) are more dissociable by attention tests than older age groups
      (12-17), indicating that changes in attention are more pronounced in the early
      years and stabilize in later years.

PMID- 18608228
TI  - Using dichotic listening to study bottom-up and top-down processing in children
      and adults.
AB  - The study examined top-down attention modulation of bottom-up processing in
      children and adults under conditions of varying bottom-up stimulus demands.
      Voiced and unvoiced consonant-vowel syllables were used in a dichotic-listening
      situation to manipulate the strength of the bottom-up stimulus-driven right ear
      advantage when subjects were instructed to focus attention on, and report, either
      the left or right ear stimulus. We predicted that children would differ from
      adults in their ability to use attention to modulate a lateralized ear advantage,
      and particularly when there was a conflict between the direction of the bottom-up
      ear advantage and the direction of the top-down attention instruction. Thirty
      children and 30 adults were presented with dichotic presentations of consonant
      vowel syllables. The results showed that the voicing manipulation affected the
      strength of the ear advantage, and that the children performed significantly
      below the adults when the voicing parameter caused a strong conflict between
      bottom-up and top down processing. Thus, children seem to lack the cognitive
      flexibility necessary to modulate a stimulus-driven bottom-up ear advantage,
      particularly in situations where right ear advantage (REA) is enhanced by the
      acoustic properties of the stimuli and attentional demands require a left ear
      shift. It is suggested that varying the stimulus demands in a dichotic-listening
      situation may be a novel way to study cognitive development.

PMID- 18608229
TI  - Neuropsychological functioning in children with medium chain acyl coenzyme a
      dehydrogenase deficiency (MCADD): the impact of early diagnosis and screening on
      outcome.
AB  - Children with medium chain acyl coenzyme A dehydrogenase deficiency (MCADD) have
      been reported to be at high risk for neurocognitive deficits. However this has
      not been systematically studied and little is known about the exact nature of
      neuropsychological sequelae or of the impact of early diagnosis and screening on
      outcome. We examined cognitive and adaptive outcome in children with MCADD (N =
      38, age range: 2 years, 2 months - 10 years, 3 months) diagnosed either through a
      newborn screening program(tandem mass spectrometry/MSMS) or upon clinical
      presentation. There was no evidence of overall intellectual impairment in either
      groups but there was some suggestion of poorer verbal and specific executive
      functioning (i.e., planning) abilities in the unscreened cohorts. Adaptive
      functioning was relatively intact with the exception of reduced Daily Living
      Skills in both our screened and unscreened groups. Early diagnosis and greater
      number of hospitalizations were related to higher verbal, communication, and
      socialization skills. Overall, our results highlight the importance of early
      diagnosis and management for children with MCADD.

PMID- 18608230
TI  - Executive functioning demands of the object retrieval task for 8- month-old
      infants.
AB  - At 8 to 11 months of age, infants are more successful in negotiating opaque
      relative to transparent barriers. However, 7-month-old infants have more
      difficulty with opaque barriers relative to semitransparent barriers. Here, 8
      month-old infants spent more time in ineffective direct reaches with more the
      transparent barriers (Experiments 1 & 2) and were faster with the fully opaque
      barrier (Experiment 2). This demonstration of the graded effects of transparency
      confirms the working memory and/or response inhibition demands of the object
      retrieval task.

PMID- 18608232
TI  - Executive functions: performance-based measures and the behavior rating inventory
      of executive function (BRIEF) in adolescents with attention deficit/hyperactivity
      disorder (ADHD).
AB  - Performance-based measures and ratings of executive functions were examined in a
      sample of adolescents with attention deficit/hyperactivity disorder (ADHD) and
      comparison controls. Performance-based measures of executive function included
      inhibition, working memory, set shifting, and planning, and ratings of these same
      executive functions were completed by parents and teachers. Adolescents with ADHD
      demonstrated lower executive function performance than controls and displayed
      elevated ratings on the executive function ratings by parents and teachers.
      Significant associations were obtained between the performance-based measures and
      the parent and teacher ratings, but each measure was not uniquely associated with
      its respective scale on the rating scales. When performance-based measures and
      ratings were examined as predictors of ADHD status, the parent and teacher
      ratings entered as significant predictors of ADHD status. Further commonality
      analyses indicated that performance-based measures accounted for little unique
      variance in predicting ADHD status and also displayed little overlap with the
      behavioral ratings. These findings highlight the diagnostic utility of behavioral
      ratings of executive function in predicting ADHD status; however, behavioral
      ratings should not be assumed to be a proxy for performance on measures of
      executive function in clinical practice.

PMID- 18608233
TI  - Comparing deaf and hearing Dutch infants: changes in the vowel space in the first
      2 years.
AB  - The influence of the mother tongue on vowel productions in infancy is different
      for deaf and hearing babies. Audio material of five hearing and five deaf infants
      acquiring Dutch was collected monthly from month 5-18, and at 24 months. Fifty
      unlabelled utterances were digitized for each recording. This study focused on
      developmental paths in vowel productions. The applied automated band filtering
      analysis is F0-independent and results in a spectral envelope, sampled in a 40
      dimensional space. Via a Principal Component Analysis (PCA, data reduction), a
      vowel space for normally hearing 2-year-olds was constructed, enabling the
      projection of the individual developmental data of the infants in a two
      dimensional reference plane. Comparison of the results for the hearing and the
      deaf infants over 2 years indicates individual as well as group differences. The
      amount of hearing loss as well as the communication styles seem to be important
      factors in explaining differences between the infant categories.

PMID- 18608235
TI  - Maori English.
AB  - The Maori language is the language of the indigenous people of New Zealand.
      Today, not all Maori speak the Maori language, and many Maori as well as non
      Maori speak Maori English, the fastest growing of the main varieties of New
      Zealand English. This paper provides a background to the linguistic situation of
      the Maori populace in New Zealand, including the current revitalization of the
      Maori language and the increasing use of Maori English. Speech-language
      therapists working with Maori clients now see children who are monolingual
      speakers of standard New Zealand English or monolingual speakers of Maori
      English, young children who are being raised as bilingual speakers of Maori and
      English, and older people who are relatively fluent in Maori.

PMID- 18608236
TI  - Transcribing disordered speech: by target or by production?
AB  - The ability to transcribe disordered speech is a vital tool for speech-language
      pathologists, as accurate description of a client's speech output is needed for
      both diagnosis and effective intervention. Clients in the speech clinic often use
      sounds that are not part of the target sound system and which may, in some cases,
      be sounds not found in natural language at all. While the IPA provides a wide
      range of symbols that can be used in clinical transcription, the extended IPA
      (extIPA) may also be needed to transcribe atypical sounds never or rarely
      encountered in natural language. When using the IPA and extIPA transcribers aim
      to show the client's productions, irrespective of the intended target. An
      alternative tradition of clinical transcription has grown up in the US: the
      symbols suggested by Shriberg and Kent (SK). In many cases, these symbols are
      designed to show the intended target with a diacritic illustrating in which way
      the realization differs from the target. In this article possible confusions that
      may occur if the SK system is used are discussed, together with problems that may
      occur when SK and IPA are used together.

PMID- 18608237
TI  - Syntactic-semantic relationships in the mental lexicon of aphasic patients.
AB  - This paper examines the relative values of syntactic-semantic relationships in
      the mental lexicon of aphasic patients, which were tested within syntagmatic and
      paradigmatic networks of lexical relations. Semantic relations, such as synonymy,
      antonomy, and hyperonymy, as well as collocational and coordinational syntactic
      semantic relations, were examined simultaneously. Twenty-five subjects diagnosed
      with nominal aphasia were tested, as well as a control group of 20 healthy
      subjects. The control group was matched with the aphasic group in terms of
      dominant hemisphere, age, sex, and job. A naming test based on semantic context
      was used in this research. The test was presented orally to subjects. After the
      examiner had read a sentence, subjects were supposed to finish it with a target
      word (the word which was, through context, in a syntactic-semantic relationship
      with the rest of the sentence). Sentences were composed of highly frequently
      occurring words. The categories used in the test were randomly patterned. The
      resultant data were analysed according to adequate semantic relations of the
      answers in the given context, and according to the type of the semantic-syntactic
      relation in 'wrong' answers. Results of this analysis are interpreted according
      to current psycholinguistic theories.

PMID- 18608238
TI  - 'Non-vocalization': a phonological error process in the speech of severely and
      profoundly hearing impaired adults, from the point of view of the theory of
      phonology as human behaviour.
AB  - 'Non-vocalization' (N-V) is a newly described phonological error process in
      hearing impaired speakers. In N-V the hearing impaired person actually
      articulates the phoneme but without producing a voice. The result is an error
      process looking as if it is produced but sounding as if it is omitted. N-V was
      discovered by video recording the speech of two groups, profoundly and severely
      hearing impaired adults in four elicitation tasks of varying difficulty, and
      analysing 2065 phonological error processes (substitutions, omissions, and N-V)
      according to 24 criteria resulting in 49,560 data points. Results, which are
      discussed in view of the theory 'Phonology as Human Behaviour' (PHB), indicate
      that: (a) The more communicative the error process was; the more effort was made
      for its production and the more frequent its distribution; (b) The easier the
      elicitation task was, the more frequent the use of communicative error processes;
      c) The more difficult the elicitation task was, the more frequent the use of the
      relatively less communicative and easier to produce error processes; and d) The
      process of N-V functioned like a communicative error process for the group of
      profoundly hearing impaired adults.

PMID- 18608239
TI  - Overcoming unintelligibility in aphasia: the impact of non-verbal interactive
      strategies.
AB  - As a follow-up to previous research, this report focuses on the wide range of
      gestures employed by an individual with aphasia to overcome instances of
      unintelligibility and re-establish intelligibility. The gestures observed are
      woven seamlessly into the fabric of the interactions and range from deictic to
      metaphorical or symbolic in nature. Specific examples are provided.

PMID- 18608240
TI  - The effect of summer vacation on bilingual preschoolers' language development.
AB  - The purpose of the investigation was to examine the developmental trajectories of
      bilingual preschoolers' comprehension of Spanish and English and to determine
      whether a lengthy summer vacation impacted children's development during the
      preschool years. Participants included 83 bilingual children who were followed
      over a 2-year period during which time children attended a federally funded
      preschool programme for children from low-income homes living in the US. Children
      were divided into two groups based on whether their scores on receptive language
      measures increased or decreased during their first year of Head Start. Results
      revealed that children whose scores increased experienced positive growth in
      their language comprehension in Spanish and English over the 2-year period,
      whereas children whose scores decreased during the first year continued to
      experience a negative developmental trajectory in their second year.
      Additionally, it was found that a lengthy summer vacation had a differential
      effect on children's development. Summer vacation had a negative effect on the
      developmental trajectories of children who experienced gains in their
      comprehension of English and Spanish and a positive impact on children whose
      scores declined during the school year. Clinical implications suggest that
      children may require differential support during the school year and summer
      vacation depending upon their developmental trajectories during the first year in
      preschool.

PMID- 18608241
TI  - Using question words or asking yes/no questions: failure and success in
      clarifying the intentions of a boy with high-functioning autism.
AB  - This paper examined the processes that resulted in an adult failing to comprehend
      the intentions of a boy with high-functioning autism. In a dyadic conversation
      between an adult and a young boy, the adult used questions to elicit
      clarification of intentions. The boy's responses were examined frame-by-frame
      using videotape microanalysis. Two causes of adult misunderstanding were
      formulaic use of words that confused the listener and directional gaze away from
      the listener. Questions that used interrogatives often failed to clarify the
      intention of the boy and yes/no questions appeared suitable to clarify his
      intention. However, success or failure to clarify an intention was not based
      solely on differences in the question format. Differences in question content may
      also have been relevant. Yes/no questions were mainly used to ask about specific
      actions. On the other hand, interrogative questions were used to handle cognitive
      or meta-cognitive matters.

PMID- 18608242
TI  - Fricatives, affricates, and vowels in Croatian children with cochlear implants.
AB  - The aim of the research was to analyse the speech of children with cochlear
      implants over approximately a 46-month period, and compare it with the speech of
      hearing controls. It focused on three categories of sounds in Croatian: vowels
      (F1 and F2 of /i/, /e/, /a/, /o/ and /u/), fricatives /s/ and /integral/
      (spectral differences expressed in terms of center of gravity), and affricates
      /ts/ and /t integral/ (accuracy, total duration, and pattern of stop-fricative
      components). One group of subjects were 10 implanted children who had been
      profoundly deaf before implantation. There were four recordings per child. Group
      two children were hearing controls matched for age and sex. The results show that
      the implanted children are closest to unimpaired children in terms of their
      formant-defined vowel space. Their fricatives exhibit poor distinction in terms
      of the noise spectrum, and the affricates are the most difficult to produce.

PMID- 18608243
TI  - The regression hypothesis revisited: evidence from Turkish.
AB  - The purpose of the study is first to investigate whether there is a significant
      difference among three study groups in terms of total content words, total
      nominal and verbal productions, and total nominal and verbal inflections; and
      secondly to analyse the most frequent words produced in relation to a picture
      description task. The underlying assumption is to analyse the tendency towards
      morpho-syntactic regression among the study groups, namely: a group of aphasics,
      a group of non-brain damaged adults, and a group of normally developing children
      still acquiring language. Participants were asked to describe two pictures of
      situations: one related with 'accidents' and the other with 'hospitals'. No
      regression was found in the group with aphasia towards the level of children in
      regard to the total number of nouns and verbs produced, save for the number of
      nominal inflections. The most frequent nouns were almost similar in the three
      groups, but qualitatively, the verbs with the highest frequency differed in the
      children.

PMID- 18608244
TI  - Voice quality of psychological origin.
AB  - Variations in voice quality are essentially related to modifications of the
      glottal source parameters, such as: F0, jitter, and shimmer. Voice quality is
      affected by prosody, emotional state, and vocal pathologies. Psychogenic vocal
      pathology is particularly interesting. In the present case study, the speaker
      naturally presented a ventricular band voice whereas in a controlled production
      he was able to use a more normal phonation process. A small corpus was recorded
      which included sustained vowels and short sentences in both registers. A normal
      speaker was also recorded in similar tasks. Annotation and extraction of
      parameters were made using Praat's voice report function. Application of the
      Hoarseness Diagram to sustained productions situates this case in the pseudo
      glottic phonation region. Analysis of several different parameters related to F0,
      jitter, shimmer, and harmonicity revealed that the speaker with psychogenic voice
      was capable of controlling certain parameters (e.g. F0 maximum) but was unable to
      correct others such as shimmer.

PMID- 18608245
TI  - Acoustics characteristics of voice and vocal care in acting and other students.
AB  - Based on voice-history data, a chi2 test was used to investigate the difference
      between students of acting (n = 45) and other students (n = 45). A t-test was
      used to calculate the differences in acoustic parameters between the two groups.
      It was expected that students of acting spent significantly more time practicing
      voice exercises, took more acting instructions, and generally spoke more in
      larger rooms and did warm up exercises (p < .001). However, it was not expected
      that they smoked more than non-professionals (p = .003), and that they drank
      alcoholic drinks as much as other students. Male students of acting had
      significantly lower f(0) SD means (p = .015), which means that they had a more
      stable pitch throughout phonation. Students of acting also showed a significantly
      higher Harmonics-to-Noise Ratio (HNR) than other students (p = .001 for males; p
      = .01 for females). The data showed the importance of the appropriate use of
      voice, which reflected relatively good voice quality despite the bad living
      habits of the future professional voice users.

PMID- 18608246
TI  - The locus equation as an index of coarticulation in syllables produced by
      speakers with profound hearing loss.
AB  - Locus equations (LEs) were derived from consonant-vowel-consonant (CVC) syllables
      produced by four speakers with profound hearing loss. Group data indicated that
      LE functions obtained for the separate CVC productions initiated by /b/, /d/, and
      /g/ were less well-separated in acoustic space than those obtained from speakers
      with normal hearing. A general trend of reduced anticipatory coarticulation was
      obtained for contexts in which speakers with normal hearing ordinarily
      coarticulate. One speaker engaged more coarticulation than did speakers with
      normal hearing. Speakers' productions could be ordered in a way that locus
      functions appeared to progressively collapse upon one another, suggesting a
      progressive reduction of consonant separation in acoustic space. The applications
      of the locus equation as an index of coarticulation and intervention outcome
      measure are discussed.

PMID- 18608247
TI  - A longitudinal study of voice before and after phonosurgery for removal of a
      polyp.
AB  - The aim of the present investigation was to evaluate the acoustic parameters,
      perceptual estimation, and self-estimation of voice before, 1 month after, and 6
      years after surgical removal of a vocal fold polyp. Subjects were five male
      patients who came to the Phoniatric Clinic because of breathiness. For all
      patients, a polyp of one vocal fold was diagnosed. The operation was performed
      using cold instruments based on the principles of contemporary phonosurgery
      aiming maximally at preserving the phonatory bridge of the vocal fold. The
      subjects were recorded in a sound-proof booth three times: before surgery, 1
      month post-, and 6 years post-operation. The patients read a short tale and they
      pronounced a sustained vowel /a/. The following variables were measured: clinical
      (the distance of the polyp from the anterior commissure, the width of the polyp
      base and the size of the polyp), and acoustic (F0, jitter, shimmer, harmonic-to
      noise ratio, voice turbulence index, degree of voice breaks, and long-term
      average spectrum). Acoustic variables were measured using the program Praat,
      while the estimation of voice quality was completed using the GRBAS scale and
      self-estimation questionnaire of the voice quality, which were answered by the
      patients. The results showed significant improvement in the variables
      investigated and improved patients satisfaction with their vocal health after the
      surgery.

PMID- 18608248
TI  - Electropalatographic (EPG) assessment of tongue-to-palate contacts in dysarthric
      speakers following TBI.
AB  - The aim of the investigation was to compare EPG-derived spatial and timing
      measures between a group of 11 dysarthric individuals post-severe TBI and 10 age-
      and sex-matched neurologically non-impaired individuals. Participants of the TBI
      group were diagnosed with dysarthria ranging from mild-to-moderate-severe
      dysarthria. Each participant from the TBI and comparison group was fitted with a
      custom-made artificial acrylic palate that recorded lingual palatal contact
      during target consonant production in sentence- and syllable-repetition tasks at
      a habitual rate and loudness level. Analysis of temporal parameters between the
      comparison and TBI groups revealed prolonged durations of the various phases of
      consonant production, which were attributed to articulatory slowness, impaired
      speech motor control, impaired accuracy, and impaired coordination of
      articulatory movements in the dysarthric speakers post-TBI. For the spatial
      measurements, quantitative analysis, as well as visual inspection of the tongue
      to-palate contact diagrams, indicated spatial aberrations in dysarthric speech
      post-TBI. Both the spatial and temporal aberrations may have at least partially
      caused the perceptual judgement of articulatory impairments in the dysarthric
      speakers.

PMID- 18608249
TI  - Speech rate in males, females, and male-to-female  transsexuals.
AB  - For clinicians treating transsexual clients it is important to address primarily
      those characteristics whose modification is most relevant to the creation of the
      desired gender presentation. The present study investigated the extent to which a
      modification of speech rate is warranted in male-to-female transsexuals.
      Comparison of speech rate measured in 100 non-transsexual males, 100 non
      transsexual females, and 28 individuals with a confirmed diagnosis of male-to
      female gender dysphoria showed no significant differences. This result suggests
      that a modification of overall speech rate in male-to-female transsexuals is not
      really indicated but does not exclude that speech rate in males and females is
      perceived differently by listeners or that gender differences exist in temporal
      aspects of speech at a micro-level.

PMID- 18608250
TI  - The co-development of speech and gesture in children with autism.
AB  - Recent interest in gesture has led to an understanding of the development of
      gesture and speech in typically developing young children. Research suggests that
      initially gesture and speech form two independent systems which combine together
      temporally and semantically before children enter the two-word period of language
      development. However, little is known about gesture development in children's
      disordered speech. This paper presents two case studies of young children with
      autism. The children are under 3 years of age and attend an intervention
      programme to facilitate their social and communication development. Early
      indications suggest that whilst both gesture and speech development is delayed in
      children with Autistic Spectrum Disorders (ASD), the developmental trajectory is
      the same as for typically developing children.

PMID- 18608251
TI  - Collaborative role construction in a conversation with dementia: an application
      of systemic functional linguistics.
AB  - This study applies the tools provided by Systemic Functional Linguistics (SFL) to
      the description of patterns in a conversation between a person with dementia and
      a person without. It shows how, in the presence of, on the one hand, considerable
      communicative and cognitive deficits, and on the other, a collaborative
      interlocutor, a person with dementia succeeds in leading and sustaining a lengthy
      conversation, and of constructing for himself a positive role in the interaction,
      namely that of the elder advising a much younger man.

PMID- 18608252
TI  - Laryngeal edema and metabolic acidosis after Omnicide ingestion.
AB  - INTRODUCTION: Glutaraldehyde and quaternary ammonium compounds are widely used as
      disinfectants and sterilizing agents. Glutaraldehyde is irritating to the eyes
      and upper respiratory tract, and has been associated with occupational asthma.
      Acute oral ingestion of a concentrated solution has not been previously reported
      in humans. CASE REPORT: A 19-year-old woman presented after deliberate ingestion
      of a biocide containing glutaraldehyde and a quaternary ammonium compound. She
      developed respiratory distress and severe metabolic acidosis 10 hours after
      admission. Marked laryngeal edema was noted when she was being intubated. She
      eventually improved following supportive care and was discharged alive after 9
      hospital days. DISCUSSION: There are no reports of acute ingestions of both
      glutaraldehyde and quaternary ammonium compounds. As both these substances are
      known to cause metabolic acidosis, localized edema, erosion and sensitization of
      both the respiratory and alimentary tract. The clinical effect may be additive or
      synergistic. CONCLUSIONS: Omnicide ingestion should be closely monitored for
      metabolic acidosis and laryngeal edema which may progress to upper airway
      obstruction requiring urgent airway stabilization.

PMID- 18608253
TI  - Human poisoning with hexastar: a hexaconazole-containing agrochemical fungicide.
AB  - We report a patient who ingested 500 ml of Hexastar 5.5% EC, a hexaconazole
      containing product. Clinical toxicity consisted primarily of central nervous
      system depression and generalized trembling. The patient recovered without
      sequelae with supportive therapy.

PMID- 18608254
TI  - Deaths from reptile bites in the United States, 1979-2004.
AB  - INTRODUCTION: Bites from reptiles cause thousands of injuries but fortunately few
      deaths in the U.S. each year. This article reviews deaths from reptile bites over
      the last 25 years. METHODS: Mortality data was obtained using CDC WONDER to
      evaluate deaths that occurred from 1979 to 2004 due to reptile bites. Information
      on race, gender, ages, and state where death occurred is reported. RESULTS: There
      were 134 deaths reported over this 25-year time period. Whites were 93.3% of the
      victims, and males were 79.1% of the victims. The age group reporting the most
      deaths was the 25 to 34 year old category. There were 17 (12.7%) victims less
      than 15 years of age, and 25 (18.7%) victims older than 65 years of age. Seventy
      five of the fatalities (55.9%) occurred in five states. CONCLUSIONS: An average
      of five deaths occurs from reptile bites each year in the U.S. White males living
      in the Southern part of the United States are more likely to be the victim of a
      fatal reptile envenomation.

PMID- 18608255
TI  - Acetaminophen protein adducts: a review.
AB  - Significant controversy surrounds the clinical and legal implications of 3-para
      cysteinyl acetaminophen, the protein degradation product of acetaminophen protein
      adducts. Versions of this test have been used for several years in animal
      research to help understand acetaminophen toxicity. As human research papers have
      appeared, the allegation has been made that the presence of 3-para cysteinyl
      acetaminophen in a patient with hepatic injury proves causal association of
      acetaminophen with the injury. It has also been suggested that quantitative
      adduct assays can guide the management of acute overdose or repeated supra
      therapeutic use of acetaminophen by determining the need for initiating therapy
      and the timing of the end of therapy. The purpose of this review is to discuss
      the nature of this molecule and the detection assay, the animal research linking
      it with injury, and to evaluate the human research--specifically the evidence
      regarding causality and clinical utility. At the current time there is inadequate
      evidence for the test alone to prove causal association between acetaminophen and
      hepatic injury. Also, since quantitative 3-para cysteinyl acetaminophen assays
      parallel other markers of liver injury, it is not clear that assays alone will
      guide therapy unless quantitative assay markers can be shown to precede other
      markers (in elevation or decline) or provide more specificity than the Rumack
      Matthew risk categorization nomogram. These advantages have not been
      demonstrated.

PMID- 18608257
TI  - Effects of adenosine receptor antagonists on amitriptyline-induced QRS
      prolongation in isolated rat hearts.
AB  - OBJECTIVE: We investigated the effects of adenosine receptor antagonists on
      amitriptyline-induced cardiotoxicity in isolated rat hearts. METHODS: The
      amitriptyline concentrations that prolonged the QRS duration more than 150% (10(
      4) M) and 50-75% (5.5 x 10(-5) M) were accepted as the control groups for two
      experimental protocols, respectively. In the first protocol, amitriptyline (10(
      4) M) was infused following pretreatment with a selective adenosine A(1) receptor
      antagonist, DPCPX (8-cyclopentyl-1,3-Dipropylxanthine,10(-4) to 10(-6) M) or a
      selective adenosine A(2a) receptor antagonist, CSC (8-3-chlorostyryl-caffeine,10(
      4) to 10(-6) M). In the second protocol, amitriptyline (5.5 x 10(-5) M) was
      infused following pretreatment with DPCPX (10(-4) M) or CSC (10(-5) M). Left
      ventricular developed pressure (LVDP), dp/dt(max), QRS duration and heart rate
      (HR) were measured. RESULTS: In the first protocol, 10(-4) M DPCPX pretreatment
      shortened QRS duration at 50 minutes when compared to the control group (p <
      0.05). In the second protocol, pretreatment with 10(-4) M DPCPX shortened the QRS
      duration at 40, 50, and 60 minutes after amitriptyline infusion when compared to
      the control group (p < 0.05, p < 0.01 and p < 0.05, respectively). Pretreatment
      with 10(-5) M CSC prolonged QRS duration at 20, 30, and 60 minutes (p < 0.05).
      Amitriptyline infusion following pretreatment with DPCPX or CSC did not change
      LVDP, dp/dt(max), or HR when compared to control in both protocols (p > 0.05).
      CONCLUSION: While 10(-4) M DPCPX shortened QRS prolongation, 10(-5) M CSC
      prolonged QRS duration in the isolated rat hearts with prolonged QRS duration
      induced by 5.5 x 10(-5)M amitriptyline. An adenosine A(1) receptor antagonist,
      DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta
      adrenergic receptors.

PMID- 18608258
TI  - Accidental human injection of Excenel RTU: ceftiofur hydrochloride in cottonseed
      oil.
AB  - INTRODUCTION: There is little knowledge within the medical community of the
      existence of veterinary antibiotics in oil-based suspensions and the adverse
      effects that may occur with accidental human injection. CASE REPORT: A farmer
      injected an unknown quantity of Excenel RTU into her right thigh. Despite early
      debridement she developed a deep infection and recurrent chronic inflammation in
      the subcutaneous tissues and muscle secondary to the cottonseed oil suspension.
      Radical debridement and extensive split skin grafting was required but she still
      has had recurrences 12 months after injury. DISCUSSION: Prompt surgical
      debridement should be performed as in cases of oil based veterinary vaccines.
      Despite being an antibiotic there is a significant risk of infection from a dirty
      needle following inoculation and multiple cultures should be taken and
      appropriate broad spectrum antibiotics used. Radical debridement and skin
      grafting necessitating specialist plastic surgical attention may be required.

PMID- 18608259
TI  - Systemic fluoride poisoning and death from inhalational exposure to sulfuryl
      fluoride.
AB  - We report a poisoning death from inhalational exposure to the gas fumigants
      chloropicrin and sulfuryl fluoride. The patient displayed both local irritant
      effects of chloropicrin and systemic effects of sulfuryl fluoride. The clinical
      course, marked by initial hypocalcemia, delayed onset of ventricular
      dysrhythmias, and death, is consistent with fluoride being the predominant
      mechanism of toxicity with sulfuryl fluoride.

PMID- 18608260
TI  - Neurotoxicity following chronic intravenous use of "Russian cocktail".
AB  - INTRODUCTION: Recently, neurological abnormalities in methcathinone users have
      been attributed to manganese. We report similar toxicity in three patients
      following the use of a mixture similar to methcathinone: potassium permanganate,
      ephedrine, and aspirin. CASE REPORTS: Three teenagers (15 to 19 years old)
      presented with extrapyramidal abnormalities and movement disorders following
      chronic intravenous use of a mixture known as "Russian Cocktail". All three
      patients had multiple movement disorders. One patient had normal blood manganese
      concentration (<19 microg/L) and MRI. The other two had elevated blood manganese
      (2100 microg/L and 3176 microg/L) and MRIs showing bilateral symmetric hyper
      intensities on T1-weighted-images in the dentate nucleus, subcortical white
      substance of cerebellar hemisphere, globus pallidus, and putamen. Abstinence and
      treatment with EDTA, levodopa, and para-aminosalicylic acid was associated with
      decreasing blood manganese concentrations and subjective improvement, but no
      change in objective findings. DISCUSSION: The "Russian Cocktail" likely contains
      manganese as a result of the oxidation of ephedrine by potassium permanganate in
      water acidified by acetylsalicylic acid. We believe that manganese with the
      possible contribution of methcathinone caused the neurological impairments.
      CONCLUSIONS: Three toxic substances have been made into a mixture administered
      intravenously, similar to methcathinone. Our patients learned of this mixture,
      called "Russian Cocktail", from their friends. The toxicity from repeated use of
      this mixture is one of extrapyramidal abnormalities and movement disorders.
      Standard therapies were unsuccessful in reversing the clinical toxicity.

PMID- 18608261
TI  - Subcutaneous silicone injection leading to multi-system organ failure.
AB  - BACKGROUND: Silicone is an inert liquid polymer often chosen for cosmetic
      procedures due to its durability and thermal stability. Following silicone
      injection, end organ toxicity can occur. We report two cases of multiorgan
      dysfunction following silicone injection. CASE REPORT: Two transsexual males
      presented to the emergency department with altered consciousness after receiving
      subcutaneous injections of silicone into the hip and buttocks. Each patient had
      received injections totaling between one and two liters of silicone. Soon after
      the injections, each reported feeling nauseated and lethargic, and then lost
      consciousness. On arrival, each was somnolent, with tachycardia and hypotension.
      Lungs were clear and there were multiple injection sites of induration noted over
      the hips and gluteal regions. Laboratory screening showed leukocytosis and
      hemoconcentration in each, with no drugs found on urine toxicology screening.
      Chemistries were normal. Both became hypoxic on arterial blood gas analysis.
      Oxygenation worsened in each despite intubation and ventilator manipulation.
      Chest radiographs were initially clear but progressively showed adult respiratory
      distress syndrome. One patient gradually improved over several days, was
      extubated, and recovered neurologically. The second patient continued to be
      hypoxic, never regained neurologic function, and expired three weeks after
      presentation. Post-mortem examination revealed clinical respiratory failure with
      organizing pneumonia, adult respiratory distress syndrome, and foreign body giant
      cell reactions to silicone. Additionally, multiple small subacute brain white
      matter infarcts consistent with silicone embolization were found. CONCLUSION:
      Clandestine application of silicone for body enhancement is common and clinicians
      should be aware of the potential complications.

PMID- 18608262
TI  - Toxicology laboratory analysis and human exposure to p-chloroaniline.
AB  - INTRODUCTION: p-Chloroaniline is more potent at producing methemoglobin than
      aniline in animal models. This case highlights the clinical presentation of an
      inhalation exposure to p-chloroaniline and associated laboratory analysis. An in
      vitro study evaluating the metabolism of p-chloroaniline in human hepatocytes was
      undertaken to evaluate the metabolic fate more closely. CASE PRESENTATION: A 20
      year-old man was working at a chemical waste plant when he developed dizziness,
      abdominal pain, and nausea. The exam was remarkable for coma, tachycardia,
      cyanosis, and pulse oximetry of 75%. Arterial blood gases showed a pH 7.38,
      pCO(2) 41 mmHg, pO(2) 497 mmHg, bicarbonate 24 mEq/L and methemoglobin 69%.
      Methylene blue administration led to complete recovery without sequelae. p
      Chloroaniline was later identified as the chemical involved. He denied direct
      contact with the chemical, but was not wearing a dust mask or respirator. GC/MS
      confirmed p-chloroaniline and metabolites in the patient's urine. METHODS: Human
      hepatocytes were incubated with 100 microM p-chloroaniline for 24 hours, in both
      rifampicin- and vehicle only-treated cells. The cell culture medium was collected
      for GC/MS analysis for p-chloroaniline metabolites. RESULTS: Similar to the
      patient sample, both p-chloroaniline and p-chloroacetanilide were identified by
      GC/MS in hepatocytes incubated with p-chloroaniline. Neither p-chloroaniline
      incubated in empty cell culture nor direct GC/MS injection of p-chloroaniline
      generated any p-chloroacetanilide via non-enzymatic degradation.
      DISCUSSION/CONCLUSION: The seemingly innocuous dermal and inhalation exposure to
      p-chloroaniline dust can lead to life-threatening methemoglobinemia. The
      diagnosis can be confirmed with GC/MS analysis of the patient's urine, searching
      for p-chloroaniline and its primary metabolite p-chloroacetanilide.

PMID- 18608264
TI  - A fatal case of sevoflurane abuse.

PMID- 18608265
TI  - Pediatric ingestion of seven lead bullets successfully treated with outpatient
      whole bowel irrigation.

PMID- 18608263
TI  - Valproic acid poisoning: an evidence-based consensus guideline for out-of
      hospital management.
AB  - A review of US poison center data for 2004 showed over 9000 ingestions of
      valproic acid. A guideline that determines the conditions for emergency
      department referral and prehospital care could potentially optimize patient
      outcome, avoid unnecessary emergency department visits, reduce health care costs,
      and reduce life disruption for patients and caregivers. An evidence-based expert
      consensus process was used to create the guideline. Relevant articles were
      abstracted by a trained physician researcher. The first draft of the guideline
      was created by the lead author. The entire panel discussed and refined the
      guideline before distribution to secondary reviewers for comment. The panel then
      made changes based on the secondary review comments. The objective of this
      guideline is to assist poison center personnel in the appropriate out-of-hospital
      triage and initial out-of-hospital management of patients with a suspected
      ingestion of valproic acid by 1) describing the process by which an ingestion of
      valproic acid might be managed, 2) identifying the key decision elements in
      managing cases of valproic acid ingestion, 3) providing clear and practical
      recommendations that reflect the current state of knowledge, and 4) identifying
      needs for research. This guideline applies to the acute ingestion and acute-on
      chronic ingestion of immediate-release and extended-release dosage forms of
      valproic acid, divalproex, and valproate sodium alone. Co-ingestion of additional
      substances could require different referral and management recommendations
      depending on the combined toxicities of the substances. This review focuses on
      the ingestion of more than a single therapeutic dose and the effects of an
      overdose. Although therapeutic doses of valproic acid can cause adverse effects
      in adults and children, some idiosyncratic and some dose-dependent, these cases
      are not considered. This guideline is based on an assessment of current
      scientific and clinical information. The expert consensus panel recognizes that
      specific patient care decisions might be at variance with this guideline and are
      the prerogative of the patient and the health professionals providing care,
      considering all of the circumstances involved. This guideline does not substitute
      for clinical judgment. Recommendations are in chronological order of likely
      clinical use. The grade of recommendation is in parentheses. 1) All patients with
      suicidal intent, intentional abuse, or in whom a malicious intent is suspected
      (e.g., child abuse or neglect) should be referred to an emergency department
      (Grade D). 2) Patients who are symptomatic (more than somnolence or exhibiting
      coma or seizures) after a valproic acid ingestion should be referred to an
      emergency department (Grade C). 3) Asymptomatic patients with an unintentional
      acute ingestion of 50 mg/kg or more or asymptomatic patients who are taking the
      drug therapeutically and who take an additional single acute ingestion of 50
      mg/kg or more of any valproic acid formulation should be referred to an emergency
      department for evaluation (Grade C). 4) Patients with unintentional ingestions of
      immediate-release valproic acid formulations, who are asymptomatic, and more than
      6 hours has elapsed since the time of ingestion, can be observed at home (Grade
      C). 5) Patients with unintentional ingestions of delayed-release or extended
      release formulations of valproic acid who are asymptomatic, and more than 12
      hours has elapsed since the time of ingestion, can be observed at home (Grade C).
      6) Pregnant women who ingest below the dose for emergency department referral and
      do not have other referral conditions should be directed to their primary care
      obstetrical provider for evaluation of potential maternal and fetal risk. Routine
      referral to an emergency department for immediate care is not required (Grade D).
      7) Do not induce emesis (Grade C). 8) Activated charcoal can be administered to
      asymptomatic patients who have ingested valproic acid within the preceding hour
      (Grade C). Prehospital activated charcoal administration, if available, should
      only be carried out by health professionals and only if no contraindications are
      present. Poison centers should follow local protocols and experience with its
      use. Do not delay transportation in order to administer activated charcoal
      (Grades D). 9) In patients who have ingested valproic acid and who are comatose,
      naloxone can be considered for prehospital administration in the doses used for
      treatment of opioid overdose, particularly if the patient has respiratory
      depression (Grade C). 10) A benzodiazepine can be administered by EMS personnel
      if convulsions are present and if authorized by EMS medical direction, expressed
      by written treatment protocol or policy, or if there is direct medical oversight
      (Grade C).

PMID- 18608266
TI  - Epidemiology of organophosphate pesticide poisoning in Taiwan.
AB  - INTRODUCTION: The nationwide epidemiology of organophosphate pesticide (OP)
      poisoning has never been reported in detail for Taiwan. METHODS: This study
      retrospectively reviewed all human OP exposures reported to Taiwan's Poison
      Control Centers (PCCs) from July 1985 through December 2006. RESULTS: There were
      4799 OP exposures. Most OP exposures were acute (98.37%) ingestions (74.50%) of a
      single OP (80.37%) to attempt suicide (64.72%) in adults (93.25%). Males were the
      most common gender (64.95%). Most patients (61.97%) received atropine and/or
      pralidoxime. The mortality rate for all 4799 OP exposures was 12.71%. Exposures
      to single OPs without co-intoxicants caused 524 deaths; of these, 63.36% were due
      to dimethyl OPs. CONCLUSION: Dimethyl OPs cause the majority of deaths in Taiwan.

PMID- 18608268
TI  - Serotonin syndrome following a single 50 mg dose of sertraline in a child.
AB  - OBJECTIVE: To report a case of serotonin syndrome associated with a single, 50 mg
      dose of sertraline in a child and discuss the findings in context with previous
      relevant literature involving other selective serotonin reuptake inhibitors used
      in children. CASE SUMMARY: A nine-year old male with chronic behavioral problems
      was prescribed oral sertraline 50 mg daily. After the first dose, the patient
      presented with abdominal pain, seizure-like activity, and change in mental
      status. He was admitted to a tertiary-care pediatric hospital and was treated for
      serotonin syndrome. Laboratory findings of elevated creatine kinase and serum
      creatinine were consistent with rhabdomyolysis as result of continued
      hypertonicity. Sertraline was discontinued and treatment with lorazepam and
      cyproheptadine was initiated. Clinical status, creatine kinase, and serum
      creatinine improved over 5 days of hospitalization. The Adverse Drug Reaction
      Probability Scale by Naranjo et al was applied to assess causality. The scale
      indicated the association of a single dose of sertraline and serotonin syndrome
      as "probable." CONCLUSION: To our knowledge this is the first reported case of
      serotonin syndrome associated with a single dose of sertraline in a child using a
      validated causality scale. The sertraline 50 mg dose given to the child was
      higher than usual recommended initial doses (25 mg). This potential adverse
      reaction should be considered when selecting antidepressant therapy for children.

PMID- 18608269
TI  - Conservative management of elemental mercury retained in the appendix.
AB  - INTRODUCTION: Few cases of mercury sequestration in the appendix appear in the
      literature. Based on these, both prophylactic appendectomy and non-surgical
      management have been recommended. We report a case in which a patient with
      mercury retained in the appendix was managed conservatively without developing
      mercurialism or appendicitis. CASE REPORT: A 43-year-old man ingested
      approximately one tablespoon of elemental mercury after an argument with his
      wife. An initial abdominal radiograph showed mercury in the pylorus of the
      stomach and a follow-up x-ray at 72 hours showed mercury localized to the
      appendix. The patient was treated as an outpatient and examined several times
      over a 37-day period. He never developed signs of appendicitis. On a follow-up
      examination 7 months after the ingestion, he was radiographically free of
      mercury. Periodically throughout his clinical course, blood mercury levels were
      obtained. Only one, 6 days after ingestion, showed an elevated mercury level of
      68 mcg/L (reference range <10 mcg/L). Despite this, the patient never developed
      signs or symptoms of mercury poisoning. CONCLUSION: Patients in whom elemental
      mercury is retained in the appendix, who are without symptoms and have normal
      gastric mucosa, may be conservatively managed without surgery.

PMID- 18608270
TI  - Antidotes and their availability in South Africa.
AB  - INTRODUCTION: The availability of antidotes is essential and often lifesaving in
      management of certain poisonings. Surveys conducted in a number of countries have
      demonstrated inadequate availability of antidotes. Since no similar studies have
      been published for South Africa, it was decided to investigate the local
      availability of antidotes. METHODS: A questionnaire on the availability of
      antidotes was sent to government and private hospital pharmacies. The list of
      commonly required antidotes and supportive agents was compiled from WHO
      guidelines. RESULTS: The response rate was 94%. None of the responding hospitals
      stocked all of the antidotes on the list. Tertiary hospitals had the highest
      percentage (67%) of antidotes available. DISCUSSION: Seven antidotes were not
      stocked by any of the hospitals, including digoxin-specific antibody fragments,
      dimercaprol, calcium disodium edetate, fomepizole, intravenous pyridoxine,
      silibinin, and succimer. Five of these are not registered as medicines in South
      Africa. CONCLUSIONS: Poison information centers should work with local drug
      coding committees to improve availability of important antidotes.

PMID- 18608271
TI  - Insecticide contamination as a cause of food related illness.

PMID- 18608272
TI  - Hypotension after ingestion of Aliskiren.

PMID- 18608273
TI  - Hypertensive crisis and NSTEMI after accidental overdose of sustained release
      pseudoephedrine: a case report.

PMID- 18608274
TI  - Intra-arterial N-acetylcysteine.

PMID- 18608275
TI  - Transdermal buprenorphine intoxication.

PMID- 18608276
TI  - Infantile lead poisoning from an Asian tongue powder: a case report & subsequent
      public health inquiry.
AB  - INTRODUCTION: Lead poisoning from novel environmental sources continues to
      present a challenge to clinicians who treat infants and children. CASE REPORT: A
      12 month old infant of Thai parents was found during well child care to have a
      venous blood lead concentration of 61 mcg/dL. He was hospitalized for parenteral
      chelation with CaNa2EDTA and subsequently managed as an outpatient with oral
      succimer, with a reduction in blood lead concentration to 23 mcg/dL. Chronic lead
      poisoning was attributed to the use of a Thai tongue powder by the parents for
      the first seven months of the infant's life. This ethnic remedy was applied to
      the tongue to absorb toxins, reduce white patches present after milk feedings,
      and preserve the infant's health. INVESTIGATIONS: Lead contaminated the powder at
      109,000 ppm as measured by x-ray fluorescence spectrometry. Two poison centers in
      Thailand were contacted and initiated a public health inquiry with the Thai Food
      & Drug Administration (Thai FDA) to remove contaminated products from the
      marketplace. Their investigation found six additional contaminated tongue powders
      (of 10 tested) in a Bangkok shop offering Chinese remedies, some with lead levels
      > 9000 ppm. These products, unregistered with the Thai FDA, were confiscated and
      the shop closed. Local media attention and case-finding activities of health
      officials identified one additional infant suffering from lead poisoning due to
      tongue powders. CONCLUSIONS: Asian tongue powders can be a source of lead
      poisoning. Medical toxicologists, poison centers, and public health agencies can
      work together internationally to accomplish effective post-marketing product
      surveillance.

PMID- 18608277
TI  - Acute tacrolimus toxicity in a non-transplant patient.
AB  - INTRODUCTION: Tacrolimus is an immunosuppressant widely used in recipients of
      solid organ transplants to prevent rejection. Toxicity is usually reported in
      transplant patients. We report the first case of tacrolimus toxicity in a non
      transplant patient. CASE REPORT: A 42 year-old, 48 kg woman complained of neck
      pain following a motor vehicle collision and was admitted for observation. On
      examination, her pulse was 112 beats/minute and her blood pressure 188/134 mmHg.
      Because the hypertension and tachycardia might be ethanol withdrawal, she was
      admitted and treated with multivitamins, folate, and thiamine in her maintenance
      fluids. She was discharged after 4 days in hospital. The day after her discharge,
      she was asked to return after it was discovered that she had inadvertently
      received tacrolimus (total of 400 mg) instead of thiamine. She was admitted with
      non-oliguric renal failure and metabolic acidosis. A tacrolimus concentration 27
      hours after her last exposure was 96.8 ng/mL (therapeutic 5 to 20 ng/mL).
      Treatment was supportive and she was discharged after 4 days without sequellae.
      DISCUSSION: Our patient's tacrolimus dose was 2.1 mg/kg/day for 4 days
      (therapeutic 0.03 to 0.05 mg/kg/day). Her tacrolimus elimination half-life was
      16.5 hours, compared to a mean half-life in healthy volunteers of 34.2 +/- 7.7
      hours. CONCLUSION: Clinical toxicity, similar to that seen in transplant
      patients, can develop in non-transplant patients following intravenous
      administration of supra-therapeutic doses of tacrolimus.

PMID- 18608278
TI  - Acute pesticide poisoning: 15 years experience of a large North-West Indian
      hospital.
AB  - INTRODUCTION: Acute pesticide poisoning is an important cause of morbidity and
      mortality in developing countries. Better preventive and management strategies
      can be developed if the incidence and pattern of acute poisoning are known.
      METHODS: This retrospective study covered 15 years (1990 to 2004). The case
      records of all cases admitted with acute poisoning during these years were
      reviewed and the results compared to earlier studies. RESULTS: A total of 2884
      patients with acute poisoning were admitted during the study period (1918 men).
      The mean age was 27.8 years (range 13 to 82 years). The commonest agents were
      anticholinesterases (35.1%) and aluminum phosphide (26.1%). A seasonal variation
      in anticholinesterase poisoning was observed (most cases occurring July to
      September) but not for aluminum phosphide. No difference in mortality was
      observed over different months for different agents. Maximum case fatality ratio
      was due to aluminum phosphide exposures followed by anticholinesterase agents.
      The case fatality ratios for aluminum phosphide and organophosphate poisonings
      declined since 2000 despite an increase in aluminum phosphide exposures. The
      decline in aluminum phosphide mortality may be due to limited availability of 3
      gm tablets and improved intensive care. CONCLUSIONS: Though incidence of acute
      pesticide poisoning increased over decades, there has been a decline in mortality
      for both aluminum phosphide and anticholinesterases. There is still need for
      measures like integrated pesticide management, development of safer aluminum
      phosphide formulations, and training of farmers in spraying techniques.

PMID- 18608280
TI  - Comment on late-onset intermediate syndrome  due to organophosphate poisoning.

PMID- 18608279
TI  - Fatal diphenhydramine poisoning with increased vascular permeability including
      late pulmonary congestion refractory to percutaneous cardiovascular support.
AB  - BACKGROUND: Fatal adult cases of acute diphenhydramine poisoning are extremely
      rare. CASE REPORT: Transiently awakened by a roommate, a 39-year-old man admitted
      to massive ingestion of an over-the-counter drug containing diphenhydramine
      salicylate. On admission the patient was semicomatose and developed circulatory
      collapse with severe dehydration and metabolic acidosis, followed by status
      epilepticus. Despite extensive life support measures including percutaneous
      cardiopulmonary support, vascular permeability progressively increased, with
      pulmonary congestion as well as peripheral vasodilation evident as rubedo. The
      patient died without improvement of cardiac function. Subsequent diphenhydramine
      assays in serum specimens obtained at the time of delayed congestive symptoms
      indicated decreases in drug concentration to a sublethal amount. DISCUSSION: We
      suspect that metabolites of diphenhydramine with histamine-agonist actions
      contributed to the development of fatal delayed symptoms.

PMID- 18608282
TI  - Colchicine-induced toxicity in a heart transplant patient with chronic renal
      failure.
AB  - Introduction. Therapeutic doses of colchicine in patients with renal compromise
      and cyclosporine therapy may result in increased plasma concentrations of
      colchicine and colchicine toxicity. Case Report. A 60-year-old heart transplant
      patient with chronic renal failure and cyclosporine-induced immunosuppression was
      started on colchicine for suspected gout. Four days later, he developed multi
      organ failure with rhabdomyolysis, liver damage, polyneuropathy, and
      cardiotoxicity. Colchicine intoxication was suspected and plasma levels were 7
      ng/mL 36 hours after the sixth dose. Neutropenia with an absolute neutrophil
      count of 700 cells/mm3 was observed five days after colchicine discontinuation.
      Drug discontinuation, supportive care, antibiotic therapy for a concurrent
      infection, and G-CSF administration resulted in recovery and he was discharged
      from the hospital 3 weeks later. Discussion. Cyclosporine co-administration
      increases colchicine toxicity by a dual mechanism: cyclosporine inhibits P
      glycoprotein resulting in increased intracellular colchicine concentrations and
      decreased hepatic and renal excretion of the drug and cyclosporine interacts with
      CYP3A4 to decreases the hepatic elimination of colchicine. On the other hand,
      colchicine may increase cyclosporine neurotoxicity by an addictive mechanism.
      Conclusions. Shortterm administration of therapeutic colchicine doses may cause
      life-threatening side effects in cyclosporine-treated patients with renal
      failure.

PMID- 18608283
TI  - Endoscopic removal of iron bezoar following acute overdose.

PMID- 18608284
TI  - Mortality and causes of death after hospital-treated self-poisoning in Oslo: a 20
      year follow-up.
AB  - INTRODUCTION: Self-poisoning is a risk factor for premature death and for
      suicide, but for how long? The aims were to examine the mortality rate, causes of
      death, and risk factors for mortality and suicide during 20 years. METHOD:
      Prospective cohort study including all patients discharged after self-poisoning
      from all medical departments in Oslo in 1980 (n = 946, 51 % females, median age
      31 years). Standardized mortality ratios (SMRs) and Cox regression analysis were
      used. RESULTS: During follow-up, 355 (37.5%) of the patients died, SMR 4.6 (95%
      CI, 4.2-5.1). After 15 years, the SMR was still 3.3 (95% C.I., 2.5-4.2). Sixty
      seven (7.1%) committed suicide, SMR 26.7 (95% CI, 21.0-33.9). The risk of death
      from all causes was significantly higher. Unspecific risk factors for death were
      found. A suicidal motive was the only risk factor for suicide. CONCLUSION: The
      mortality rate implies a poor prognosis in this patient group.

PMID- 18608287
TI  - Atypical sources of childhood lead poisoning in the United States: a systematic
      review from 1966-2006.
AB  - BACKGROUND: Lead poisoning from atypical sources, which excludes the well
      established lead-based paint ingestions and exposure in occupational settings,
      are increasingly reported in medical literature. Our objective is to increase
      awareness on atypical sources of lead exposure and to formulate recommendations
      for their detection based on actual reported cases. METHODS: We systematically
      retrieved and reviewed reports on pediatric lead poisoning in the U.S. from
      atypical sources by searching Medline, Embase, CINAHL, Academic Search Premier,
      AltHealth, websites of state lead poisoning prevention programs, and the U.S.
      Consumer Product Safety Commission database for reports published from January
      1966 to December 2006. RESULTS: We retrieved 28 published reports that met our
      inclusion criteria. Of these reports, 20 are case reports and 8 case series,
      documenting a total of 82 incidents of lead poisoning in children from atypical
      sources. CONCLUSION: There are varied sources of atypical lead exposure among
      U.S. children. The sources were grouped in the following categories based on
      their utility: fashion accessories, folk remedies, imported condiments & candies,
      pellets & bullets, and lastly, recreational & domestic items. Based on these
      findings, we have formulated a questionnaire that may assist in the
      identification of atypical lead sources in the home.

PMID- 18608288
TI  - Hepatitis induced by Teucrium viscidum.
AB  - INTRODUCTION: In Hong Kong, Chinese medicine is popular and coexists with
      orthodox Western medicine. Despite a long history of use, many herbs have not
      been submitted to rigorous scientific testing and there are reports of
      hepatotoxicity. We describe a woman who developed acute hepatitis after drinking
      an herbal remedy containing Teucrium viscidum. CASE REPORT: A previously healthy
      51-year-old woman was admitted to a regional hospital because of jaundice, with
      complaints of nausea, vomiting, and tea-colored urine for three days prior to
      admission. She denied any recent ingestion of known hepatotoxins, but she had
      consumed an herbal remedy for low back pain for three days before the onset of
      symptoms. She was icteric and had a serum total bilirubin level of 11.4 mg/dL,
      alanine aminotransferase of 2620 U/L, aspartate aminotransferase of 1876 U/L, and
      alkaline phosphatase level of 186 U/L. Discontinuation of the herbal remedy
      resulted in normalization of the liver enzymes two months later. DISCUSSION: This
      is the first report of hepatitis probably related to use of Teucrium viscidum.
      The herb is infrequently used in Chinese medicine for treatment of rheumatic and
      bleeding disorders. T. viscidum contains teucvin, similar to other Teucrium
      species and is related to T. chamaedrys, commonly known as germander, which is a
      well documented cause of hepatotoxicity. CONCLUSIONS: Our findings suggest that
      Teucrium viscidum can cause hepatotoxicity similar to that of germander.

PMID- 18608290
TI  - Recurrent hemorrhage after western diamondback rattlesnake envenomation treated
      with crotalidae polyvalent immune fab (ovine).
AB  - INTRODUCTION: Recurrent coagulopathy has been observed in patients after
      rattlesnake envenomation treated with Crotalidae Polyvalent Immune Fab (ovine)
      [FabAV]. While recurrent coagulopathy is well documented in the literature,
      clinically significant sequelae have not been reported. We present a case of
      recurrent thrombocytopenia after western diamondback envenomation treated with
      FabAV, resulting in an extensive recurrent local hemorrhage. CASE REPORT: A 24
      year-old male presented to our emergency department several hours after western
      diamondback envenomation. He sustained bites to both hands and the right flank by
      leaning over his pet "snake enclosure." On presentation, the patient was
      hypotensive, tachycardic, and thrombocytopenic with a platelet count of 17/nl.
      Antivenom therapy was initiated according to the standard FabAV protocol.
      However, sixteen hours after completion of the recommended FabAV infusion, the
      patient experienced a recurrent thrombocytopenia with a dramatic seventeen point
      drop in hematocrit. The source of bleeding was clinically attributed to an
      expanding hematoma at the site of envenomation. DISCUSSION: FabAV has become the
      standard treatment for symptomatic crotalid envenomation. However, the
      pharmacokinetics of this drug predispose it to recurrent coagulopathies. While
      studies have shown persistent and recurrent coagulopathic derangements after
      FabAV therapy, no clinically significant sequelae have been reported. This report
      highlights the potential for recurrent local hemorrhagic complications following
      rattlesnake envenomation, even after treatment guided by the current FabAV
      protocol. CONCLUSIONS: Recurrent coagulopathy following FabAV therapy can result
      in clinically significant hemorrhage, supporting the observation that extended
      repeat dosing may be necessary to adequately treat subjects of rattlesnake
      envenomation.

PMID- 18608295
TI  - Cerebral air gas embolism from concentrated hydrogen peroxide  ingestion.
AB  - INTRODUCTION: Ingestion of a small amount of concentrated hydrogen peroxide can
      cause cerebral air gas embolism (CAGE). Hyperbaric oxygen therapy (HBOT) is the
      standard of care in the treatment of CAGE. We report a case of CAGE after
      accidental ingestion of 33%hydrogen peroxide treated with HBOT resulting in
      reversal of both the clinical and radiologic abnormalities. CASE REPORT: A 48
      year-old male took two sips of 33% hydrogen peroxide. A short time later, he
      developed hematemesis, left sided hemiplegia, confusion, and left homonymous
      hemianopsia. Initial laboratory studies, chest x-ray, and brain CT were normal.
      MRI demonstrated areas of restricted diffusion and T2 hyper intensities in
      multiple vascular territories consistent with ischemia due to CAGE. Eighteen
      hours after arrival, the patient underwent HBOT at 3 atmospheres absolute (ATA)
      for 30 minutes and 2.5 ATA for 60 minutes with clinical improvement. Follow-up
      MRI at six months demonstrated resolution of the hyper intensities. DISCUSSION: A
      search of MEDLINE from 1950 to present revealed only two cases of CAGE from
      ingestion of concentrated hydrogen peroxide treated with HBOT. Both cases,
      similar to ours, had complete resolution of symptoms. Of the seven reported cases
      of CAGE from hydrogen peroxide that did not undergo HBOT, only in one patient was
      there a report of symptom resolution. CONCLUSION: Ingestion of even a small
      amount of concentrated hydrogen peroxide can result in cerebral air gas embolism.
      Hyperbaric oxygen therapy may be of benefit in reversing the symptoms and
      preventing permanent neurological impairment.

PMID- 18608296
TI  - Ingestions of benzydamine-containing vaginal preparations.
AB  - OBJECTIVE: Benzydamine is a non-steroidal antiinflammatory drug used as vaginal
      lavage for non-specific vaginitis. Data on overdoses are scarce despite its wide
      availability. METHODS: Retrospective analyses of single ingestions of benzydamine
      vaginal irrigation products from January 1991 to December 2003 reported to the
      Spanish Poison Control Centre. RESULTS: 724 cases met the inclusion criteria;
      86.2% of the patients were over age 14 years. Gender was not a factor in young
      children but 80.9% of patients older than 14 years were female. In 85.9% of
      cases, benzydamine was ingested when it was mistaken for an oral preparation or
      for an oral antiseptic. The rest were unintentional exposures in children (13.8%)
      or suicidal attempts (0.3%). Clinical signs or symptoms, when present, were
      mainly gastrointestinal (48% of symptomatic patients) followed by neurological
      (31%) or both (21%). The most common symptom was nausea (32.8% of symptomatic
      patients) followed by vomiting (27.9%), dizziness (20.1%), hallucinations
      (15.3%), abdominal pain (13.4%), and esophageal irritation and agitation (10.5%,
      each). Six of 68 children (mean age 6.2, range 3-11 years) had hallucinations. A
      severe case was that of a 4-year-old child who had convulsions caused by the
      unintentional ingestion of benzydamine. CONCLUSION: This is the largest report of
      benzydamine ingestions. The outstanding feature was the high percentage of
      neurological manifestations in children and adults, mainly hallucinations,
      following the ingestion of an over-the-counter product.

PMID- 18608297
TI  - Envenomation by a wild Guatemalan Beaded Lizard Heloderma  horridum
      charlesbogerti.
AB  - BACKGROUND: The Guatemalan Beaded Lizard (Heloderma horridum charlesbogerti) is
      an endemic venomous lizard that inhabits southeastern Guatemala. Published
      reports of bites by Beaded Lizard are scarce. This is the first case report of a
      bite from Heloderma horridum charlesbogerti. CASE REPORT: A 24-year-old man was
      bitten on the left hand by a juvenile Heloderma horridum charlesbogerti. The
      lizard remained attached for approximately 15 seconds. The patient experienced
      severe local pain, dizziness, diaphoresis, vomiting, severe paresthesia in his
      left hand and arm, and hypotension (70/52 mm/Hg). He was treated with intravenous
      ketorolac, chlorpheniramine, methylprednisolone, antibiotics, ondansentron, and
      normal saline. Hematology tests revealed leukocytosis (12,600/mm3). Symptoms
      improved and the patient was discharged from hospital 24 hours after admission.
      CONCLUSION: The case reported here shows that bites by Heloderma produce severe
      clinical effects shortly after the bite. Management consists of waiting for the
      lizard to relax its bite pressure and using pliers to open lizard's mouth and
      pull out the bitten extremity, a careful manual search for teeth remnants, and
      supportive care. In our case, severe pain, unresponsive to non-steroidal anti
      inflammatory analgesics, was a major problem. Parethesias resolve quickly but
      pain may persist for up to 12 hours after the bite. A full recovery is expected.

PMID- 18608299
TI  - Iatrogenic intravenous medication errors reported to the PIC Erfurt.
AB  - BACKGROUND: We investigated the iatrogenic intravenous medication errors (IIME)
      reported to the Poisons Information Center (PIC) Erfurt. METHODS: All IIME over a
      ten year period were analyzed retrospectively and categorized into error types,
      age groups, drugs involved, and estimated risk of toxicity. RESULTS: From 1997 to
      2006 the PIC Erfurt registered 132 cases of IIME. They increased from 7 in 1997
      to 31 in 2006. Children accounted for 31.1% of the patients affected and adults
      for 68.9%. The drug classes (ATC classification) involved most frequently were
      antipsychotics (9.8%) and antihistamines for systemic use (7.5%). The main types
      of IIME were overdose (53.1%) and incorrect route of administration (29.7%). The
      estimated risk of toxicity was: 14.4% none, 71.2% risk of toxicity, and 14.4%
      unpredictable risk. Medical treatment was recommended in 82%. The outcome of 104
      of the 132 (78.8%) courses was unknown. In the 28 cases followed to a known
      outcome, 9 (32%) were asymptomatic and 19 (68%) symptomatic with minor (9 cases),
      moderate (1 case), and severe features (6 cases) but mostly complete recovery.
      Two IIME resulted in hypoxia-induced brain damage and one in death despite of
      resuscitation. CONCLUSION: Approximately 0.1% of all calls registered by the PIC
      Erfurt from 1997 to 2006 concerned IIME. Thirty-two percent of IIME followed to a
      known outcome resulted in severe symptoms. These data show that IIME can be
      harmful.

PMID- 18608300
TI  - Pediatric plant exposures in Germany, 1998-2004.
AB  - INTRODUCTION: Each year, 80,000 to 100,000 calls to the Poison Information
      Centres (PIC) concern pediatric exposures in Germany. Plant exposures are the
      fourth most common category, accounting for 22% of pediatric exposures. METHODS:
      Information on plant exposures in children (0-14 years) was collected from annual
      reports of German PIC. The severity of pediatric plant exposures was classified
      using the number of ingestions and a calculated hazard factor. RESULTS: A total
      of 58,641 cases involving 248 different plant genera were reported from 1998 to
      2004. Most plant exposures were not associated with clinical effects at time of
      call, but 9.6% of cases had noticeable effects, including 0.4% classified as
      moderate and major effect. CONCLUSIONS: The majority of plant genera have low
      hazard factors. Most severe poisoning (highest hazard factors and exposures) in
      children involved Brugmansia, Laburnum, Phaseolus, and Thuja.

PMID- 18608301
TI  - Bites and stings by exotic pets in Europe: an 11 year analysis of 404 cases from
      Northeastern Germany and Southeastern France.
AB  - INTRODUCTION: The presence of exotic, and sometimes venomous, pets in European
      homes is becoming more common. This phenomenon is the basis of a French-German
      cooperative evaluation of the species causing the injuries and the circumstances,
      severity, and treatment of the envenomations METHODS: A retrospective,
      descriptive, cross-sectional, case series of data from 1996 to 2006. The study
      sample consists of all cases of bites and stings by exotic pets that were
      registered at four poisons European poisons centers. The inclusion criteria were
      bites and stings of human beings. RESULTS: From 1996 to 2006 four poisons centers
      in Europe were consulted on 404 bites and stings by exotic pets. The average age
      of the patients was 36 (2 to 75) years and 73% of the patients were male. The
      severity of the envenomations, according to the Poisoning Severity Score, was as
      follows: 29 severe (7.1%), 55 moderate (14.2%) and 320 minor (78.7%). There were
      no fatalities in this case series. Exotic snakebites from rattlesnakes, cobras,
      mambas, and other venomous snakes caused 39% of envenomations, aquatic animals
      (mostly lionfish of the Pterois genus and stingrays) caused 30% of envenomations
      and arthropods (tarantulas and scorpions) caused 27% of envenomations. All severe
      envenomations were caused by venomous snakes. CONCLUSIONS: European healthcare
      professionals may encounter patients bitten or stung by exotic pets. Poisons
      center consultation can help manage these unusual presentations and help obtain
      rarely used antivenoms.

PMID- 18608303
TI  - Oral tetridamine exposures.
AB  - OBJECTIVE: Tetridamine is a non-steroidal anti-inflammatory drug of the class
      indazols used topically as co-adjuvant for vaginitis. No previous data have been
      published about tetridamine overdoses. METHODS: Retrospective analysis of single
      ingestions of tetridamine vaginal douches reported to the Spanish Poison Control
      Centre from January 1991 to December 2003. RESULTS: Seventy-seven cases met the
      inclusion criteria; 89.6% of the patients were over age 14 years. Exposures
      primarily involved female patients (94.4%). In 87% of cases, the tetridamine was
      ingested when it was mistaken for an oral preparation or for an oral antiseptic.
      The rest were unintentional exposures in children (10.4%) or suicide attempts
      (2.6%). Clinical effects, present in 17 patients, were mainly gastrointestinal
      (11 patients) followed by neurological (3 patients) or both (3 patients). The
      most common symptom was vomiting, followed by nausea, abdominal pain, and
      headache. One woman who ingested 4 g in a suicidal attempt became comatose.
      CONCLUSION: This is the first report of tetridamine overdoses. An effort should
      be made by physicians and pharmacists to explain clearly the correct directions
      for the use of vaginal irrigation preparations.

PMID- 18608305
TI  - Acute poisoning by pirimicarb: clinical and toxicological features.
AB  - OBJECTIVE: Anticholinesterase compounds like organophosphorous and carbamates
      account for the majority of poisonings by the insecticides class agents. While
      the toxicokinetic depends on the extent of exposure and also on the chemical
      structure of the agent, the clinical symptoms range from the classic cholinergic
      syndrome to flaccid paralysis and intractable seizures. The carbamate ester
      pirimicarb (Pirimor), a toxic N-dimethylcarbamate pesticide, is used as
      insecticide. Our case presents the first poisoning associated with clinical and
      analytical findings. PATIENT: A 68-year-old male ingested an unknown amount of
      pirimicarb and developed cholinergic symptoms immediately, accompanied by
      seizures. INTERVENTIONS: He was admitted in the Intensive Care Unit (ICU) and
      received intensive care including intubation for hypoxemia following seizures and
      drug therapy of hypertensive dysregulation. No Atropine but benzodiazepines were
      administered. The patient recovered in the ICU after 3 days and was discharged
      after a week. MEASUREMENTS AND RESULTS: Pirimicarb stomach, blood, and urine
      levels were determined on admission and during hospitalisation. Using an one
      compartment model the pesticide elimination was estimated and its terminal half
      life in plasma, t1/2, was found to be 3.8 hours. The butyryl cholinesterase
      (BChE) activity was at the lower level of detection on the admission and
      recovered during the following 24 hours.

PMID- 18608309
TI  - Can imaginal exposure reduce intrusive memories in depression? A case study.
AB  - The presence of intrusive memories as an overlapping feature of depression and
      posttraumatic stress disorder (PTSD) raises the possibility that common
      therapeutic approaches may be effective. Imaginal exposure (IE) is the gold
      standard treatment for PTSD and directly reduces both PTSD and depression
      symptoms in traumatized individuals. The objective of this pilot study was to use
      a single-case design to trial the use of IE to target intrusive memories of a
      negative life event as a treatment for major depression. The participant was
      experiencing depression after a relationship breakup. Pre-posttreatment measures
      (clinical interview and self-report) showed a decrease in frequency of intrusive
      memories and improved mood, such that the participant no longer met diagnostic
      criteria for major depression at posttreatment or at 6-month follow-up. This case
      is an important first step in demonstrating the possible value of IE as an
      inclusion in therapy to reduce intrusive memories in patients whose depressive
      episode is precipitated by a stressor. Further application of IE to additional
      depressed clients in the context of a case series is needed to provide
      preliminary evidence of its efficacy as a treatment for depressive disorders.

PMID- 18608310
TI  - The effectiveness of cognitive behavioral therapy for generalized anxiety
      disorder in a frontline service setting.
AB  - The goal of the current study was to test the generalizability of cognitive
      behavioral therapy (CBT) for generalized anxiety disorder (GAD) in a frontline
      service setting. Twenty-nine patients who presented to treatment clinics with
      problematic worry were provided CBT for GAD. Among the intent-to-treat sample,
      there were no significant changes in worry or depression from pre- to
      posttreatment. Treatment completers showed significant pre- to posttreatment
      reductions on measures of worry and depression. The magnitude of change was
      smaller than has been reported in randomized control trials (RCTs). Although the
      frontline service setting differed from RCT settings in multiple ways, treatment
      completers nonetheless achieved moderate to large decreases in self-reported
      worry and depression.

PMID- 18608311
TI  - Group cognitive behavioural therapy for depression outcomes predicted by
      willingness to engage in homework, compliance with homework, and cognitive
      restructuring skill acquisition.
AB  - There is a need to understand the mechanism through which homework contributes to
      clinically meaningful change in therapy. Theoretically meaningful factors such as
      willingness to complete therapeutic assignments and cognitive skill acquisition
      have not been carefully studied in prior research. Depressed outpatients (N = 46)
      received cognitive behavioural group therapy for a 10-week period and were
      assigned relevant homework activities. Patient self-report and independent
      ratings of homework compliance were obtained on a session-by-session basis. Using
      path analysis, the authors found evidence that willingness to complete homework
      assignments and mastery of skill in cognitive restructuring helped account for
      the relationship between homework compliance and reduced symptom severity (R2 =
      .40). However, paths were only significant when patient self-report of homework
      compliance was used in the model. The present study highlights the problems in
      assessing homework compliance and in assuming that independent assessment of
      compliance is more accurate than patient self-report.

PMID- 18608312
TI  - Can exposure and acceptance strategies improve functioning and life satisfaction
      in people with chronic pain and whiplash-associated disorders (WAD)? A randomized
      controlled trial.
AB  - Although 14% to 42% of people with whiplash injuries end up with chronic
      debilitating pain, there is still a paucity of empirically supported treatments
      for this group of patients. In chronic pain management, there is increasing
      consensus regarding the importance of a behavioural medicine approach to symptoms
      and disability. Cognitive behaviour therapy has proven to be beneficial in the
      treatment of chronic pain. An approach that promotes acceptance of, or
      willingness to experience, pain and other associated negative private events
      (e.g. fear, anxiety, and fatigue) instead of reducing or controlling symptoms has
      received increasing attention. Although the empirical support for treatments
      emphasizing exposure and acceptance (such as acceptance and commitment therapy)
      is growing, there is clearly a need for more outcome studies, especially
      randomized controlled trials. In this study, participants (N = 21) with chronic
      pain and whiplash-associated disorders were recruited from a patient organization
      and randomized to either a treatment or a wait-list control condition. Both
      groups continued to receive treatment as usual. In the experimental condition, a
      learning theory framework was applied to the analysis and treatment. The
      intervention consisted of a 10-session protocol emphasizing values-based exposure
      and acceptance strategies to improve functioning and life satisfaction by
      increasing the participants' abilities to behave in accordance with values in the
      presence of interfering pain and distress (psychological flexibility). After
      treatment, significant differences in favor of the treatment group were seen in
      pain disability, life satisfaction, fear of movements, depression, and
      psychological inflexibility. No change for any of the groups was seen in pain
      intensity. Improvements in the treatment group were maintained at 7-month follow
      up. The authors discuss implications of these findings and offer suggestions for
      further research in this area.

PMID- 18608313
TI  - Treatment of panic disorder with agoraphobia: randomized placebo-controlled trial
      of four psychosocial treatments combined with imipramine or placebo.
AB  - Few randomized controlled trials have included panic disorder patients with
      moderate to severe agoraphobia. Therefore, this population was studied using
      pharmacotherapy as well as psychotherapy. At the time of the study, imipramine
      was widely used as a pharmacological treatment. Also, current practice guidelines
      for patients with panic disorder find selective serotonin reuptake inhibitors and
      tricyclic antidepressants roughly comparable in terms of efficacy. Therefore, the
      main objective of this study is to compare four psychosocial treatments-cognitive
      and graded in vivo exposure treatments, graded in vivo exposure, cognitive
      treatment, and supportive therapy-to evaluate the benefits of combining cognitive
      therapy with exposure in vivo. These treatments were combined with imipramine or
      placebo for a total of eight experimental conditions. Participants presented
      moderate to severe agoraphobia. The method involved a randomized, double-blind,
      placebo-controlled trial with 137 participants who completed a 14-session
      protocol involving the treatments just mentioned. Measures were taken at baseline
      and posttreatment and at 3-, 6-, and 12-month follow-up. All treatment conditions
      were statistically and clinically effective in reducing self-reported panic
      agoraphobia symptoms over the 1-year follow-up. No statistical differences were
      observed between imipramine and placebo conditions. This study found that all
      treatment modalities helped reduce panic and agoraphobic symptomatology over a 1
      year follow-up period. These surprising results support the need to document the
      relations among the various components of an intervention. This would make it
      possible to assess the relative efficacy of the treatment components rather than
      of the intervention as a whole.

PMID- 18608314
TI  - Frequency and nature of rumination in chronic depression: a preliminary study.
AB  - This study explores the phenomenological experience of rumination in a sample of
      22 chronically depressed people and looks at the extent to which it is consistent
      with theoretical ideas. The findings indicate that, on average, depressed people
      ruminate about at least two different topics, and that there is wide variability
      in how long each episode lasts. Rumination is a complex process frequently
      involving imagery as well as verbal thoughts and is almost invariably associated
      with multiple emotions. Although there was some evidence for stop rules being
      involved, most individuals attributed ending a period of rumination to
      distraction, whether external or internally generated.

PMID- 18608315
TI  - Implicit memory bias for eating- and body appearance-related sentences in eating
      disorders: an application of Jacoby's white noise task.
AB  - Jacoby's white noise task and an explicit recognition task were used to
      investigate whether individuals with eating disorders demonstrate implicit memory
      bias and explicit memory bias, respectively, for information related to eating
      and body appearance. Included were 33 women with eating disorders (seven with
      anorexia nervosa and 26 with bulimia nervosa), 29 with nonclinical eating
      disorder-related concerns, and 36 healthy controls. Results showed partial
      support for implicit memory bias but no support for explicit memory bias. These
      findings suggest that eating disorders may be characterized by relative initial
      automatic bias for eating disorder-relevant information but not by bias at later
      stages of information processing. However, previous studies have demonstrated
      explicit memory bias in eating disorders, which is inconsistent with this
      interpretation. Future research is required to clarify the precise cognitive
      biases associated with eating disorders.

PMID- 18608316
TI  - A test of the validity of the motivational interviewing treatment integrity code.
AB  - To evaluate the Swedish version of the Motivational Interviewing Treatment Code
      (MITI), MITI coding was applied to tape-recorded counseling sessions. Construct
      validity was assessed using factor analysis on 120 MITI-coded sessions.
      Discriminant validity was assessed by comparing MITI coding of motivational
      interviewing (MI) sessions with information- and advice-giving sessions as well
      as by comparing MI-trained practitioners with untrained practitioners. A
      principal-axis factoring analysis yielded some evidence for MITI construct
      validity. MITI differentiated between practitioners with different levels of MI
      training as well as between MI practitioners and advice-giving counselors, thus
      supporting discriminant validity. MITI may be used as a training tool together
      with supervision to confirm and enhance MI practice in clinical settings. MITI
      can also serve as a tool for evaluating MI integrity in clinical research.

PMID- 18608317
TI  - Motion-induced positional biases in the flash-lag configuration.
AB  - When both stationary and moving objects are present in the visual field,
      localizing objects in space may become difficult, as shown by illusory phenomena
      such as the Frohlich effect and the flash-lag effect. Despite the efforts to
      decipher how motion and position information are combined to form a coherent
      visual representation, a unitary picture is still lacking. In the flash-lag
      effect, a flash presented in alignment with a moving stimulus is perceived to lag
      behind it. We investigated whether this relative spatial localization (i.e.,
      judging the position of the flash relative to that of the moving stimulus) is the
      result of a linear combination of two absolute localization mechanisms--that is,
      the coding of the flash position in space and the coding of the position of the
      moving stimulus in space. In three experiments we showed that (a) the flash is
      perceived to be shifted in the direction of motion; (b) the moving stimulus is
      perceived to be ahead of its physical position, the forward shift being larger
      than that of the flash; (c) the linear combination of these two shifts is
      quantitatively equivalent to the flash-lag effect, which was measured
      independently. The results are discussed in relation to perceptual and motor
      localization mechanisms.

PMID- 18608320
TI  - Testing computational models of letter perception with item-level event-related
      potentials.
AB  - In the present study, online measures of letter identification were used to test
      computational models of letter perception. Event-related potentials (ERPs) were
      recorded to letters and pseudoletters revealing a transition from feature
      analysis to letter identification in the 100-200-ms time window. Measures
      indexing this transition were then computed at the level of individual letters.
      Simulations with several versions of an interactive-activation model of letter
      perception were fitted with these item-level ERP measures. The results are in
      favour of a model of letter perception with feedforward excitatory connections
      from the feature to the letter levels, lateral inhibition at the letter level,
      and excitatory feedback from the letter to the feature levels.

PMID- 18608319
TI  - Searching for the elusive neural substrates of body part terms: a
      neuropsychological study.
AB  - Previous neuropsychological studies suggest that, compared to other categories of
      concrete entities, lexical and conceptual aspects of body part knowledge are
      frequently spared in brain-damaged patients. To further investigate this issue,
      we administered a battery of 12 tests assessing lexical and conceptual aspects of
      body part knowledge to 104 brain-damaged patients with lesions distributed
      throughout the telencephalon. There were two main outcomes. First, impaired oral
      naming of body parts, attributable to a disturbance of the mapping between
      lexical-semantic and lexical-phonological structures, was most reliably and
      specifically associated with lesions in the left frontal opercular and
      anterior/inferior parietal opercular cortices and in the white matter underlying
      these regions (8 patients). Also, 1 patient with body part anomia had a left
      occipital lesion that included the "extrastriate body area" (EBA). Second,
      knowledge of the meanings of body part terms was remarkably resistant to
      impairment, regardless of lesion site; in fact, we did not uncover a single
      patient who exhibited significantly impaired understanding of the meanings of
      these terms. In the 9 patients with body part anomia, oral naming of concrete
      entities was evaluated, and this revealed that 4 patients had disproportionately
      worse naming of body parts relative to other types of concrete entities. Taken
      together, these findings extend previous neuropsychological and functional
      neuroimaging studies of body part knowledge and add to our growing understanding
      of the nuances of how different linguistic and conceptual categories are operated
      by left frontal and parietal structures.

PMID- 18608321
TI  - We're getting warmer--characterizing the mechanisms of face recognition with
      acquired prosopagnosia: a comment on Riddoch et al. (2008).

PMID- 18608322
TI  - Grasping Weber's illusion: The effect of receptor density differences on grasping
      and matching.
AB  - Weber found that distances between tactile stimuli on a high-receptor-density
      area are perceived as being larger than identical distances on a low-receptor
      density area (Weber's illusion). Previous studies of visual illusions suggest
      that illusion effects vary with the type of response given. Here we tested a
      modified version of Weber's illusion in which a solid object was placed on the
      forearm or hand. Blindfolded participants were required either to give a size
      estimation or to grasp the object. The results showed that size estimation of
      solid objects was consistent with Weber's illusion, whereas grasping responses
      showed an opposite pattern (e.g., larger hand opening for objects on the
      forearm). A second experiment showed that this pattern is not due to
      biomechanical differences induced by the difference in spatial position of the
      target objects on the hand and arm. We suggest that the larger grip aperture when
      grasping objects on the arm were due to an increase in safety margin as a
      response to greater uncertainty about the object dimensions due to reduced
      receptor density.

PMID- 18608323
TI  - Hypnotizability-related integration of perception and action.
AB  - Hypnotizability is a cognitive trait able to modulate many
      behavioural/physiological processes and associated with peculiar functional
      characteristics of the frontal executive system. This review summarizes
      experimental results on hypnotizability-related differences in sensorimotor
      integration at a reflex and an integrated level (postural control) and suggests
      possible interpretations based on morpho-functional considerations. In
      particular, hypnotizability-related differences in spinal motoneurones
      excitability are described, and the role of attention and imagery in maintaining
      a stable upright stance when sensory information is reduced or altered and when
      attention is absorbed in cognitive tasks is discussed as a function of hypnotic
      susceptibility. The projections from prefrontal cortex to spinal motoneurones and
      the balance between the activation of the right and left cortical hemisphere are
      considered responsible for the hypnotizability-related modulation of reflex
      responses, while the differences in postural control between subjects with high
      (highs) and low (lows) hypnotic susceptibility are considered a possible
      consequence of the activity of the locus coeruleus, which is also involved in
      attention, and of the cerebellum, which might be responsible for different
      internal models of postural control. We suggest a highly pervasive role of
      hypnotic susceptibility in human behaviour through the modulation of the
      integration of perception and action, which could be relevant for
      neurorehabilitative treatments and for the adaptation to special environments.

PMID- 18608324
TI  - Praxic and executive components in tool use learning: the role of imitation.
AB  - Recent research in comparative psychology suggests that similarities between the
      behaviour of two individuals may not be the consequence of imitation only, but
      also of nonimitative social-learning processes. In the present study we aimed to
      investigate whether these alternative learning processes can take place in human
      adults, specifically in patients whose ability to imitate has been reduced by
      brain damage. Left (LBD) and right (RBD) brain-damaged patients were asked to
      perform four tool use tasks in three experimental conditions: exposure to the
      apparatus (N); demonstration of the correct solution (C); and demonstration of a
      failed attempt followed by the correct solution to the problem (I + C). Results
      suggest that the left hemisphere is indeed critical for action and that selective
      neuropsychological deficits can affect action imitation and selection of goal
      directed movements, independently from each other. Findings also indicate that
      when the ability to imitate actions is lowered emulation may become available.

PMID- 18608329
TI  - The effect of action goal hierarchy on the coding of object orientation in
      imitation tasks: evidence from patients with parietal lobe damage.
AB  - In order to explore parietal patients' difficulties in the processing of
      orientation information, we asked parietal patients (N = 8) and healthy and brain
      damaged controls to imitate multicomponent actions where object orientation was
      one component. In Experiment 1 orientation was not the most relevant aspect of
      the action to be imitated, and the parietal group showed significant difficulties
      in processing object orientation. However, in Experiment 2, where orientation was
      placed at the top end of the goal hierarchy, the parietal group were able to
      process stimulus orientation sufficiently to place it within the goal hierarchy
      of the action and to reproduce it accurately. We conclude that patients with
      parietal lesions might be able to include object orientation in a goal hierarchy,
      but if their processing of orientation information is impaired they might be
      disproportionately prone to errors when object orientation is lower in the goal
      hierarchy and so not prioritized for processing resources.

PMID- 18608330
TI  - Planning movements well in advance.
AB  - It has been suggested that the metrics of grasping movements directed to visible
      objects are controlled in real time and are therefore unaffected by previous
      experience. We tested whether the properties of a visually presented distractor
      object influence the kinematics of a subsequent grasping movement performed under
      full vision. After viewing an elliptical distractor object in one of two
      different orientations participants grasped a target object, which was either the
      same object with the same orientation or a circular object without obvious
      orientation. When grasping the circular target, grip orientation was influenced
      by the orientation of the distractor. Moreover, as in classical visuomotor
      priming, grasping movements were initiated faster when distractor and target were
      identical. Results provide evidence that planning of visually guided grasping
      movements is influenced by prior perceptual experience, challenging the notion
      that metric aspects of grasping are controlled exclusively on the basis of real
      time information.

PMID- 18608331
TI  - Uneven integration for perception and action cues in children's working memory.
AB  - We examined the development of visual cue integration in a desktop working-memory
      task using boxes with different visual action cues (opening actions) and
      perceptual surface cues (colours, monochromatic textures, or images of faces).
      Children had to recall which box held a hidden toy, based on (a) the action cue,
      (b) the surface cue, or (c) a conjunction of the two. Results from three
      experiments show a set of asymmetries in children's integration of action and
      surface cues. The 18-24-month-olds disregarded colour in conjunction judgements
      with action; 30-36-month-olds used colour but disregarded texture. Images of
      faces were not disregarded at either age. We suggest that 18-24-month-olds'
      disregard of colour, seen previously in reorientation tasks (Hermer & Spelke,
      1994), may represent a general phenomenon, likened to uneven integration between
      the dorsal and ventral streams in early development.

PMID- 18608332
TI  - Threat perception and targeting: The brainstem-amygdala-cortex alarm system in
      action?
AB  - Optimizing our responses to physical threats is of clear adaptive value, yet
      influences of threat perception specific to visual guidance of action have
      received little attention. Here, we assess effects of threat perception on a
      targeting task, finding improved performance for peripheral targets relative to
      central targets. These effects of threat were absent either when the task did not
      involve targeting or when targeting followed high-arousal, positive-valence
      stimuli. Additionally, the effects of threat showed a nasal- versus temporal
      visual hemifield asymmetry and were absent when target stimuli isolated S-cone
      photoreceptor function. These findings suggest that the superior colliculus,
      which is activated following threat perception, shows clear visual-field
      asymmetry, receives no direct S-cone-based inputs from the retina, and forms part
      of a hypothesized direct brainstem-amygdala-cortex alarm system, mediates this
      effect.

PMID- 18608333
TI  - Action without perception in human vision.
AB  - In 1992, David Milner and I (Goodale & Milner, 1992) proposed a division of
      labour in the visual pathways of the primate cerebral cortex between a dorsal
      stream specialized for the visual control of action and a ventral stream
      dedicated to constructing our percepts of the visual world. Support for the
      perception-action distinction has come from neuroimaging experiments, human
      neuropsychology, and monkey neurophysiology. Differences in the timing and
      spatial metrics of vision-for-perception and vision-for-action have been studied
      in human psychophysical experiments, particularly in those that have looked at
      the way in which each system deals with pictorial illusions. Although the
      literature is not free from controversy, a large number of studies have found
      that actions such as grasping and reaching are often unaffected by high-level
      pictorial illusions, which by definition affect perception. Recent experiments
      have shown that for actions to escape the effects of such illusions, however,
      they must be highly practised actions, preferably with the right hand, and must
      be directed in real time at visible targets. But even though the behavioural
      evidence suggests that the dorsal and ventral streams make use of different
      timing, different metrics, and different frames of reference in carrying out
      their computations, there is a seamless interaction between the two streams in
      the production of adaptive behaviour. A full understanding of the integrated
      nature of visually guided behaviour will require that we specify the nature of
      the interactions and information exchange that occur between these two streams of
      visual processing.

PMID- 18608334
TI  - Behavioural and neurophysiological evidence of semantic interaction between
      iconic gestures and words.
AB  - We report two experiments that provide converging behavioural and
      neurophysiological evidence on the relationship between the meaning of iconic
      gestures and words. Experiment 1 exploited a semantic priming paradigm and
      revealed interference between gestures and words when they were not related in
      meaning, but no facilitation when they were. This result was confirmed in
      Experiment 2, where ERPs were recorded during silent word reading with the same
      paradigm. The analysis showed a negative deflection peaking near 400 ms (N400)
      and, in the left hemisphere, greater negative values for verbs than for nouns.
      Differently from the classical distribution obtained with verbal stimuli, we
      found an N400 that spread more over central-anterior areas of the scalp,
      suggesting that the meaning systems of gesture and language do not overlap
      completely. These results are consistent with the view that the meaning systems
      for gesture and speech are tightly integrated.

PMID- 18608338
TI  - A patient-specific finite element methodology to predict damage accumulation in
      vertebral bodies under axial compression, sagittal flexion and combined loads.
AB  - Due to the inherent limitations of DXA, assessment of the biomechanical
      properties of vertebral bodies relies increasingly on CT-based finite element
      (FE) models, but these often use simplistic material behaviour and/or single
      loading cases. In this study, we applied a novel constitutive law for bone
      elasticity, plasticity and damage to FE models created from coarsened pQCT images
      of human vertebrae, and compared vertebral stiffness, strength and damage
      accumulation for axial compression, anterior flexion and a combination of these
      two cases. FE axial stiffness and strength correlated with experiments and were
      linearly related to flexion properties. In all loading modes, damage localised
      preferentially in the trabecular compartment. Damage for the combined loading was
      higher than cumulated damage produced by individual compression and flexion. In
      conclusion, this FE method predicts stiffness and strength of vertebral bodies
      from CT images with clinical resolution and provides insight into damage
      accumulation in various loading modes.

PMID- 18608339
TI  - Periosteal biaxial residual strains correlate with bone specific growth rates in
      chick embryos.
AB  - It has been proposed that periosteal residual tensile strains influence
      periosteal bone apposition and endochondral ossification. The role of bone growth
      rates on the development of residual strains is not well known. This study
      examined the relationships between specific growth rate and residual strains in
      chick tibiotarsi. We measured length and circumference during embryonic days 11
      20 using microCT. Bones grew faster in length, with longitudinal and
      circumferential specific growth rates decreasing from 17 to 9% and 14 to 8% per
      day, respectively. To calculate residual strains, opening dimensions of incisions
      through the periosteum were analysed using finite element techniques. Results
      indicate that Poisson's ratio for an isotropic material model is between 0 and
      0.04. For the model with Poisson's ratio 0.03, longitudinal and circumferential
      residual strains decreased from 46.2 to 29.3% and 10.6 to 3.9%, respectively,
      during embryonic days 14-20. Specific growth rates and residual strains were
      positively correlated (p<0.05).

PMID- 18608340
TI  - An algorithm for bone mechanoresponsiveness: implementation to study the effect
      of patient-specific cell mechanosensitivity on trabecular bone loss.
AB  - The rate of bone loss is subject to considerable variation between individuals.
      With the 'mechanostat' model of Frost, genetic variations in bone
      mechanoresponsiveness are modelled by different mechanostat 'setpoints'--which
      may also change with age or disease. In this paper, the following setpoints are
      used: epsilonmin (strain below which resorption is triggered); epsilonmax (strain
      above which deposition occurs); omegacrit (microdamage-level above which damage
      stimulated resorption occurs). To simulate decreased mechanosensitivity,
      epsilonmax is increased. Analyses carried out on a simplified model of a
      trabecula show that epsilonmax is a critical parameter: if it is higher in an
      individual (genetics) or increases (with age) the mass deficit each remodelling
      cycle increases. Furthermore, there is a value of epsilonmax above which
      trabecular perforation occurs, leading to rapid loss of bone mass. Maintaining
      bone cell mechanosensitivity could therefore be a therapeutic target for the
      prevention of osteoporosis.

PMID- 18608341
TI  - Modelling and convergence in arterial wall simulations using a parallel FETI
      solution strategy.
AB  - Arterial walls are characterised by nearly incompressible, anisotropic,
      hyperelastic material behaviour. Several polyconvex material functions
      representing such materials are considered and adjusted to experimental data. For
      all of these functions and for different parameter sets numerical simulations
      using a three-dimensional model of a diseased artery are performed. A finite
      element tearing and interconnecting-dual primal domain decomposition algorithm is
      used to solve the linearised systems of equations. The numerical performance of
      the different models is discussed with respect to convergence of the linear and
      nonlinear solvers.

PMID- 18608345
TI  - Sexuality, culture and society: shifting paradigms in sexuality research.
AB  - Over the course of the past three decades, there has been a significant increase
      of research on the social and cultural dimensions of sexuality. This paper
      reviews three major phases in the development of this work. In the first phase,
      work focusing on the social construction of sexual experience developed an
      important critique of the biomedical and sexological approaches that had
      dominated the field over much of the twentieth century. In the second phase,
      increasingly detailed studies of sexual life were developed which highlighted the
      cross-cultural diversity of sexual cultures, sexual identities and sexual
      communities. In the most recent phase, there has been a growing recognition of
      the complex relationship between culture and power, and increasing attention to
      the political and economic dimensions of sexuality. In spite of the significant
      conceptual and methodological advances that have taken place over time, however,
      it is also possible to identify a number of important questions that have not yet
      been adequately addressed and that may have been precluded by some of the
      perspectives that have come to dominate the field. The paper ends by focusing on
      the silences and invisibilities that continue to characterize this field of
      research and the challenges that must still be confronted in seeking to expand
      our understanding of these issues.

PMID- 18608346
TI  - Bodies, pleasure and displeasure.
AB  - In sociology and cultural studies, the body is often treated only as a symbolic
      space, as a surface on which sexual meanings are written and from which they are
      read. Realist philosophy of science and philosophy of mind, however, do not treat
      discursive meaning as arbitrary and disconnected from the material universe.
      Using a realist framework, this paper examines areas of collision between values
      and beliefs about matters of fact concerning men's and women's sexual bodies and
      sexual pleasure and displeasure. Groups campaigning for and against male
      circumcision do not argue directly against each other. The first draw on health
      justifications, while the latter raise difficulties about human rights and loss
      of sexual sensitivity. Measuring penile sensitivity proves to be difficult. When
      sexual satisfaction is understood as traditional masculine role adequacy in
      reproductive coitus, there is no way of understanding complaints about loss of
      receptive sensuality. Debates about the structure and nomenclature of the
      clitoris, about the existence of female ejaculation and about the evolutionary
      function of the female orgasm similarly founder when the protagonists do not
      share a conceptual framework: macroscopic anatomic structures and physiological
      processes become invisible to observers and false assumptions are made, for
      example about when and how orgasm occurs. Most sexual difficulties are not
      physical dysfunctions, but failures to meet social rules of sexual behaviour. In
      conclusion, the paper draws attention to issues insufficiently addressed in
      contemporary sexuality studies and calls for practical engagement by social
      researchers with public health and policy.

PMID- 18608347
TI  - Bone marrow stromal cell therapy improves femoral bone mineral density and
      mechanical strength in ovariectomized rats.
AB  - BACKGROUND: This study aimed to determine the influence of bone marrow stromal
      cells (BMSC) on the degree and sustainability of ovariectomy-induced bone loss.
      METHODS: Allogenic BMSC were injected into either the left or right femur of 15
      ovariectomized rats (OVX). Saline was injected into the contralateral femur as a
      vehicle control. Five rats were killed at 8 weeks and 5 rats at 24 weeks. The
      other five OVX rats received serial injections 4 weeks after the first injection
      and were killed 24 weeks after the first injection. To confirm osteoporotic
      model, five rats received sham operation. Bone mineral density (BMD) was measured
      using dual-energy X-ray absorptometry. Mechanical properties were evaluated by
      three-point bending. RESULTS: The OVX rats showed significantly lower BMD
      compared with that of the sham operated rats. BMD at the femoral mid-shaft was
      significantly greater in the BMSC-injected bones compared with the control bones.
      At week 8, ultimate load and stiffness were also improved in the BMSC-injected
      bones compared with controls. At 24 weeks, the stiffness of control and BMSC
      injected bones was statistically indistinguishable. The additional injection
      aided preservation of both BMD and mechanical properties. DISCUSSION: The present
      study suggests that bone strength may be improved by direct BMSC injection.

PMID- 18608348
TI  - Insufficient ex vivo expansion of Valpha24(+) natural killer T cells in malignant
      lymphoma patients related to the suppressed expression of CD1d molecules on
      CD14(+) cells.
AB  - BACKGROUND: Valpha24(+) natural killer T (NKT) cell is a human counterpart of
      mice Valpha14(+) NKT cell that has a regulatory role for innate and acquired
      potential antitumor activity. The efficient expansion of NKT cells is an obstacle
      to the clinical application of Valpha24(+) NKT cells for immunotherapy. METHODS:
      We used mononuclear cells (MNC) obtained from the peripheral blood (PB) of normal
      healthy donor (HD) and malignant lymphoma (ML) patients before and after
      granulocyte colony-stimulating factor (G-CSF) treatment. MNC were cultured for 12
      days with alpha-galactosylceramide (100 ng/mL) and interleukin-2 (IL-2; 100
      U/mL). RESULTS: The fold expansion of Valpha24(+) NKT cells was higher in HD than
      in ML patients (208 versus 0.00), despite comparable numbers of Valpha24(+) NKT
      cells before culture. G-CSF administration enhanced the predominance of
      Valpha24(+) NKT cell fold expansion in HD compared with ML patients (1935 versus
      1.95). After treatment with G-CSF, the expression of CD1d molecules was up
      regulated in CD14(+) cells from HD but not ML patients. The fold expansion of
      Valpha24(+) NKT cells and CD1d expression on CD14(+) cells was strongly
      correlated in both HD and ML patients (r(2)=0.84). However, replacement of a
      patient's CD14(+) cells with HD cells did not increase the efficacy of
      Valpha24(+) NKT cell expansion. DISCUSSION: G-CSF-mobilized PB from ML patients
      has inhibitory characteristics for Valpha24(+) NKT cell expansion as a result of
      both monocytes and Valpha24(+) NKT cells. Multiple procedures would be needed for
      the expansion of patients' Valpha24(+) NKT cells.

PMID- 18608349
TI  - Cryopreserved human bone marrow mononuclear cells as a source of mesenchymal
      stromal cells: application in osteoporosis research.
AB  - BACKGROUND: Mesenchymal stromal cells (MSC) are an invaluable tool for research
      and therapeutic application regarding degenerative diseases such as osteoporosis.
      METHODS: Human MSC from cryopreserved mononuclear (c-MSC) cell populations were
      isolated from bone marrow (BM) and compared with MSC isolated directly from the
      same BM for immunophenotype, differentiation capacity and Parathormone (PTH)
      response. RESULTS: c-MSC showed a similar immunophenotype, division and
      differentiation capacity as standard MSC obtained from the same BM. This capacity
      was maintained during various culture-growing passages. Treatment with PTH(1-34)
      from days 6 to 24, after c-MSC induction to osteoblasts and adipocytes, had no
      significant effect on osteoblastogenesis yet inhibited adipogenesis. This effect
      was similar in MSC from the same BM. DISCUSSION: We propose cryopreservation of
      mononuclear cells obtained from BM as a simple and convenient means for routine
      storage of MSC to be used for therapeutic and research applications.

PMID- 18608350
TI  - Cellular magnetic resonance imaging: potential for use in assessing aspects of
      cardiovascular disease.
AB  - There is rapidly increasing interest in the use of magnetic resonance imaging
      (MRI) to track cell migration in vivo. Iron oxide MR contrast agents can be
      detected at micromolar concentrations of iron, and offer sufficient sensitivity
      for T2*-weighted imaging. Cellular MRI shows potential for assessing aspects of
      cardiovascular disease. Labeling in vivo and tracking macrophages using iron
      oxide nanoparticles has been a goal for cellular MRI because macrophages play a
      pivotal role in the pathophysiology of many human diseases, including
      atherosclerosis. Cellular MRI has also been using to track transplanted
      therapeutic cells in myocardial regeneration. This review looked at iron oxide
      nanoparticles, methods of cell labeling, image acquisition techniques and
      limitations encountered for visualization. Particular attention was paid to stem
      cells and macrophages for the cardiovascular system.

PMID- 18608351
TI  - Isolation of oligodendrocyte-like cells from human umbilical cord blood.
AB  - BACKGROUND: As human umbilical cord blood (UCB) is known to be a rich source of
      progenitor cells, the prospect of isolating a subset of these cells that could
      differentiate into cells of non-hematopoietic lineages suggests a therapeutic use
      for patients with inherited lysosomal and peroxisomal storage diseases currently
      treated with UCB transplantation. METHODS: Oligodendrocyte-like cells were
      isolated from UCB by density-gradient centrifugation and expanded using selective
      media. We then characterized this population of cells using standard
      immunohistochemical staining methods for neural cell proteins and polymerase
      chain reaction (PCR) to detect RNA sequences for myelin basic protein (MBP). We
      also developed a functional assay demonstrating myelination of neurons in vitro.
      RESULTS: Cells with oligodendrocyte-like morphology were reproducibly cultured ex
      vivo from fresh human UCB. Cells stained positively for multiple oligodendria
      cell markers (O1, MBP and CNPase) via immunohistochemical staining and flow
      cytometry. PCR confirmed the presence of MBP and CNPase mRNA. A further in vitro
      functional assay demonstrated the myelination of mature neuronal cells from the
      brain of a myelin-deficient murine model co-cultured with the oligodendrocyte
      like cells. DISCUSSION: After human UCB transplant, donor-derived cells have been
      noted to migrate to the brain over time. Although is not known whether these
      cells solely deliver enzyme replacement or a subset engrafts and differentiates
      into mature neural cells, the clinical improvements noted in these patients
      suggest a potential role for targeted cellular therapy. Oligodendrocyte-like
      cells isolated ex vivo and expanded from human UCB could provide a potential
      cellular therapy for patients with demyelinating or dismyelinating diseases.

PMID- 18608352
TI  - The co-transplantation of human bone marrow stromal cells and embryo olfactory
      ensheathing cells as a new approach to treat spinal cord injury in a rat model.
AB  - BACKGROUND: Both bone marrow stromal cells (BMSC) and olfactory ensheathing cells
      (OEC) have been demonstrated experimentally as promising for therapy of spinal
      cord injury (SCI). However, clinical use may be constrained by the margin
      neuronal differentiation capacity of BMSC as well as the limited number of
      isolatable OEC. This study therefore tested the efficacy of co-grafting human
      BMSC and OEC in treating thoracic SCI. METHODS: Rat SCI models were created with
      cushion forces. OEC were labeled with Hoechst 33342 and BMSC with BrdU or GFP.
      BMSC, OEC and BMSC plus OEC were injected into the injured sites of rat spinal
      cords. Histologic, electrophysiologic and functional approaches were applied to
      assess the effects of transplantation of these cell types. RESULTS: Behavioral
      evaluation showed an improvement in animals with all cell-based treatments. The
      co-graft led to significantly higher gait scaling. The latency of transcranial
      magnetic motor-evoked potential (tcMMEP) responses was also better restored in
      the co-graft group. Larger numbers and sizes of axon bundles through the
      transitional zone between the normal and injured regions were observed in the co
      graft animals in comparison with all other animals. Transplanted bone marrow
      stromal cells were identified as neurofilament-positive in the co-grafted animals
      although the number of glial fibrillary acidic protein-positive cells remained
      the same in all groups. DISCUSSION: Taken together, our results suggest that the
      combined use of BMSC and OEC may provide an improved approach for the treatment
      of SCI.

PMID- 18608353
TI  - Immuno-inflammatory regulation effect of mesenchymal stem cell transplantation in
      a rat model of myocardial infarction.
AB  - BACKGROUND: Mesenchymal stem cells (MSC) have recently been shown to possess
      immunomodulatory properties in vitro and in vivo. The present study aimed to
      investigate the regulatory effect of MSC transplantation on the immuno
      inflammatory response in myocardial infarction (MI). METHODS: MI was induced in
      Sprague-Dawley rats by left anterior descending coronary artery ligation, and the
      animals were randomly assigned into the following three groups: sham ( n=8);
      phosphate-buffered saline (PBS) injected (MI+PBS, n=8); and MSC transplantation
      (MI+MSC, n=8). BrdU-labeled MSC or PBS was transplanted into peri-infarct
      myocardium by direct myocardial injection. At 1 and 28 days post-transplantation,
      cardiac function was evaluated by echocardiography. Transplanted cells were
      investigated through immunohistochemistry. Lymphocyte cytotoxic activity was
      evaluated with the crystal violet method. The activity of NF-kappaB and protein
      expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL
      10 in myocardium were assessed by immunohistochemistry and Western blot. RESULTS:
      Echocardiographic examination revealed that the MSC transplantation prevented
      left ventricular dilation and dysfunction at 28 days after the operation. BrdU
      stained cells were found living in host heart 4 weeks after transplantation. MSC
      transplantation attenuated the cytotoxic activity of spleen lymphocytes.
      Transplantation of MSC inhibited the activity of NF-kappaB, attenuated the
      protein production of TNF-alpha and IL-6, and increased the expression of IL-10
      in peri-infarct myocardium. DISCUSSION: MSC transplantation modulated the immuno
      inflammatory response in MI. The immuno-inflammatory regulatory effect of MSC
      transplantation might partly account for the cardiac protection in myocardial
      infarction.

PMID- 18608354
TI  - The role of stem cell mobilization regimen on lymphocyte collection yield in
      patients with multiple myeloma.
AB  - BACKGROUND: The lymphocyte dose (LY-DO) infused during an autograft influences
      absolute lymphocyte (ALC) recovery and survival following autologous stem cell
      transplantation (ASCT) in multiple myeloma (MM) patients. Factors influencing
      lymphocyte yield (LY-C) during leukapheresis have been poorly studied. METHODS:
      Factors that could influence survival, LY-C and CD34(+) cell yield were analyzed
      in 122 MM patients. Three mobilization regimens were used, granulocyte-colony
      stimulating factor (G-CSF) alone (n=13), cyclophosphamide 1-2 g/m(2) plus G-CSF
      (LD-CY, n=62) and cyclophosphamide 3-4 g/m(2) and G-CSF (ID-CY, n=47). RESULTS:
      Using multivariate analysis, age, LY-C, ALC on day 30 (ALC-30) and International
      Staging System stage significantly influenced overall (OS) and progression-free
      survival (PFS) following ASCT. PFS (56 versus 29 months, P=0.05) and OS (72
      versus 49 months; P=0.07) were longer in the LY-C>or=0.12x10(9)/kg group than the
      LY-C<0.12x10(9)/kg group. LY-C also influenced ALC on day 15 (ALC-15).
      Mobilization regimen, lymphocytes on the day of leukapheresis, prior radiotherapy
      and number of leukaphereses significantly influenced LY-C. Significantly higher
      LY-C was obtained with G-CSF alone compared with the LD-CY and ID-CY groups.
      CD34(+) count on the day of leukapheresis, prior chemotherapy with prednisone,
      cyclophosphamide, adriamycin and BCNU or melphalan, and stem cell mobilization
      regimen significantly influenced CD34(+) cell yield. DISCUSSION: LY-C influenced
      ALC-15 and survival following ASCT. Factors that influenced CD34(+) cell yield
      and LY-C during leukapheresis were different. Mobilization should be tailored to
      maximize the LY-C and CD34(+) cell yield.

PMID- 18608355
TI  - Psychosocial and intellectual functioning in childhood narcolepsy.
AB  - PURPOSE: This study reports the psychological assessment of 12 children referred
      to a narcolepsy clinic, using quantitative methods to describe intellectual and
      psychosocial functioning in childhood narcolepsy. METHODS: The participants were
      six males and six females aged between 7-16 years (median age 10 years). The
      protocol included a clinical interview; the Wechsler Intelligence Scale for
      Children-III-UK; and the Parent version of the Achenbach Child Behaviour
      Checklist (CBCL). RESULTS: Eleven children obtained an IQ in the average range
      (mean and median =100). However, a significant difference was found between
      verbal and performance scales in 42% of children, compared to WISC-III normative
      prevalence rates of 24%. CBCL results revealed that 10/12 children scored in the
      clinically significant range on the Total Score Index, with 9/12 obtaining scores
      in the significant range on the Internalizing Index. The majority of children
      presented with difficulties in discussing and describing distressing physical and
      psychological symptoms with parents and others. CONCLUSIONS: These findings
      suggest that the psychosocial impact of narcolepsy extends beyond the effects of
      excessive sleepiness and that symptoms such as hallucinations can lead to
      significant psychological morbidity.

PMID- 18608356
TI  - Developing and maintaining of user-defined personal competencies among young
      adults with congenital physical disability.
AB  - Outcomes from a developmental instructional training course for youths with
      congenital physical disability have been investigated for the purpose of
      clarifying whether or not the participants' personal competencies in terms of
      living an independent life were developed and whether or not these competencies
      were maintained after termination of the project. In the course of the
      intervention, there was focus on user involvement and each participant defined
      his own occupational performance problems, articulated specific goals for the
      intervention and evaluated the results by means of the Canadian Occupational
      Performance Measure (COPM). Eight young adults participated in the course from 16
      26 months with a follow-up evaluation 10-20 months later. Changes in COPM scores
      on performance and satisfaction indicate that the participants developed personal
      competencies and that it was possible to maintain some of these competencies
      after completion of the course.

PMID- 18608357
TI  - Visuo-motor coordination in 8-year-old children born pre-term before and after 28
      weeks of gestation.
AB  - PURPOSE: This study compared the visuo-motor abilities between pre-term and full
      term children. METHODS: Twenty-three 8-year-old children participated, five being
      born under 28 weeks gestational age (wGA) referred to as Preterms1 (mean=8 years
      5 months [SD 0.3]), nine Preterms2 of 28-35 wGA (mean=7 years 9 months [SD 0.7])
      and nine typically developing full-term controls (mean=8 years 6 months [SD
      0.7]). All children were studied in an interhemispheric transfer time and in a
      visuo-manual pointing-task to test motor programming time in three conditions:
      unimanual pointing (dominant, non-dominant hands), mirror bimanual pointing (same
      direction for both hands) and opposite bimanual pointing. RESULTS: Significant
      differences were detected between Preterms 1 and 2, the latter being similar to
      controls. Preterms1 presented increases in interhemispheric time, suggesting an
      alteration in the transcallosal pathways. Programming time was significantly
      lengthened (p50.01) for dominant hand unilateral pointing and opposite bilateral
      pointing and it was the shortest for mirror pointing. CONCLUSIONS: A faulty
      programming of visuo-manual tasks is suspected in Preterms1 with potential
      difficulty inhibiting the non-dominant limb mirror movement. This may result from
      an impaired interhemispheric inhibition owing to potential corpus callosum
      thinning. Such measures may be used to help follow-up subtle changes in fine
      motor control and detect pre-terms at risk of developing long-term deficits.

PMID- 18608358
TI  - Intra-individual variability in recovery from paediatric acquired brain injury:
      relationship to outcomes at 1 year.
AB  - OBJECTIVE: To determine the relationship between the amount of intra-individual
      variability in measures of abilities and participation throughout the first 8
      months of recovery from ABI and outcome scores at 1 year. Greater amounts of
      intra-individual variability throughout recovery are hypothesized to predict
      better outcome scores at 1 year. RESEARCH DESIGN: This is a secondary data
      analysis of a longitudinal cohort study. METHODS: Eighty-seven children and
      youths were assessed with self and proxy report measures of child functioning,
      family functioning and environmental factors at regular intervals after ABI.
      Mixed-effects modelling was used to determine individual linear recovery
      trajectories. Intra-individual variability was defined as the intra-individual
      standard deviation of the residuals around the recovery line. RESULTS: Less intra
      individual variability in recovery predicts better outcomes of physical health
      (Child Health Questionnaire), behavioural functioning (Strengths and Difficulties
      Questionnaire), family coping (Impact on Family Scale) and impact of
      environmental barriers (Craig Hospital Inventory of Environmental Factors). As
      amount of intra-individual variability increases, outcomes become poorer.
      CONCLUSIONS: Findings support the existence of intra-individual variability in
      instrument scores over time in this sample and the impact of this variability on
      several outcomes at 1 year. Potential clinical and research implications are
      discussed.

PMID- 18608359
TI  - General practitioners and long-term neurological conditions.
AB  - PURPOSE: General practitioners (GPs) can have a significant role to play in the
      management of individuals with long-term neurological conditions (LTNC). This
      paper looks at various roles and responsibilities of GPs in the management of
      these patients. METHOD: This paper is based on a Medline literature search using
      the key words 'general practitioner;''rehabilitation;''long-term;' and
      'neurological'. RESULTS: The findings are broadly divided into diagnostic,
      supportive and palliative roles. CONCLUSION: GPs have a lot to offer individuals
      with LTNC, but recent changes in the way they work, especially in the UK, may
      hamper their role.

PMID- 18608360
TI  - Pusher behaviour: a critical review of controversial issues.
AB  - Despite an increasing interest by researchers and clinicians, the pusher
      behaviour (PB) is still a poorly understood disorder, exhibited by some stroke
      patients, who push with their non-affected limbs towards the contralesional side
      and resist attempts at correction of their tilted posture. This review is aimed
      at critically summarizing findings on controversial issues regarding PB, namely
      correlation with neglect, neural correlates and underlying mechanisms. There is a
      growing agreement that PB reflects some misrepresentation of verticality.
      According to different findings, it has been suggested that PB may result from a
      conflict between an intact visual and an impaired somesthetic perception of
      vertical, or alternatively that it might result from a high-order disruption of
      somesthetic information processing from the paretic hemi-body, named graviceptive
      neglect. Although conflicting data have been reported, the association between PB
      and neglect seems to be confirmed, when a comprehensive assessment of neglect
      related phenomena is performed. Localization of brain lesions is also
      controversial. Some investigations stressed the role of posterior lateral
      thalamus, but other findings revealed that different lesional sites may also be
      present. On the basis of these data we suggest the existence of a
      multicomponential network reliable for upright posture control. This model might
      also explain some different results in this area. Clinical implications and
      requirements for future research are discussed.

PMID- 18608361
TI  - Social adjustment at school: Are children with cerebral palsy perceived more
      negatively by their peers than other at-risk children?
AB  - PURPOSE: To compare three dimensions of social adjustment (social status,
      friendship and victimization) across four groups of children between the ages of
      nine and 12 who differ by their birth status (premature vs. at term) and the
      presence or absence of a motor impairment (with and without cerebral palsy [CP]).
      METHOD: All premature (n = 72) and term children (n = 118) without CP and all
      children with CP (premature with CP: n = 49; term with CP: n = 29) are part of a
      follow-up study. Social adjustment measures were obtained by conducting a
      classwide sociometric interview in the class of the target child. RESULTS:
      Irrespective of their birth status, girls with CP have more social adjustment
      problems than those without a disability. With respect to victimization, the
      results show that, irrespective of gender, both CP children and premature
      children (without CP) differ from their term peers (without CP). CONCLUSIONS: By
      comparing the four groups, we are able to qualify the impact of a visible
      clinical impairment such as CP versus that of extreme prematurity on social
      adjustment.

PMID- 18608362
TI  - High volume image guided injections in chronic Achilles tendinopathy.
AB  - PURPOSE: To determine the effectiveness of high volume image guided injections
      (HVIGI) for chronic Achilles tendinopathy. METHODS: We included in the study 30
      consecutive patients (mean age 37.2 years, range 24 - 58 years) with Achilles
      tendinopathy for a mean of 35.8 months (range 2 - 276 months) who had failed to
      improve after a three-month programme of eccentric loading of the gastro-soleus
      complex. Patients were injected with 10 ml of 0.5% Bupivacaine Hydrochloride, 25
      mg Hydrocortisone acetate, and up to 40 ml of injectable normal saline. A study
      specific questionnaire and the Victorian Institute of Sport Assessment - Achilles
      tendon (VISA-A) were retrospectively administered to assess short- and long-term
      pain and functional improvement. RESULTS: Some 21 patients (70%) responded.
      Patients reported significant short-term improvement at 4 weeks of both pain
      (mean change 50 mm, [SD 28, p < 0.0001], from a mean of 76 mm [SD 18.2], to a
      mean of 25 mm [SD 23.3]), and function scores (mean change 51 mm, [SD 31.2, p <
      0.0001], from a mean of 78 mm [SD 20.8], to a mean of 27 mm [SD 28.4]). Patients
      also reported significant long-term improvement in symptoms using the VISA-A
      questionnaire (mean change 31.2 points, [SD = 28, p < 0.0001], from a mean of
      44.8 points [SD 17.7], to a mean of 76.2 points [SD 24.6]) at a mean of 30.3
      weeks from the injection. CONCLUSIONS: HVIGI significantly reduces pain and
      improves function in patients with resistant Achilles tendinopathy in the short-
      and long-term.

PMID- 18608363
TI  - Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot
      study.
AB  - BACKGROUND AND PURPOSE: Arthroscopic repair of rotator cuff tears can produce
      excellent results. The application of platelet rich plasma during arthroscopic
      rotator cuff repair is safe, and produces results which do not deteriorate over
      time. METHODS: A total of 14 patients undergoing arthroscopic repair of a rotator
      cuff tear received an intra-operative application of autologous platelet rich
      plasma in combination with an autologous thrombin component after tear repair.
      Following the procedure, patients were given a standardized rehabilitation
      protocol, and followed for 24 months. Outcome measures included a pain score
      (VAS) as well as functional scoring (UCLA and Constant scores). RESULTS: Of the
      original 14 patients, 13 were seen at a final follow-up appointment 24 months
      after the index operation. Patients demonstrated a significant decrease in VAS
      scores and significant increases in the UCLA and Constant scores at 6, 12 and 24
      month follow-ups compared to a pre-operative score. CONCLUSION: No adverse events
      related to this application were noted during the procedure. The application of
      platelet rich plasma during arthroscopic rotator cuff repair is safe and
      effective, and produces results which seem to be stable with time. A prospective
      randomized investigation will be necessary to ascertain the efficacy of platelet
      rich plasma application to improve or expedite the surgical outcome following
      arthroscopic rotator cuff repair.

PMID- 18608364
TI  - Dysfunctional turning in Parkinson's disease.
AB  - PURPOSE: People with Parkinson's disease (PD) frequently freeze or fall turning:
      They turn slowly taking numerous steps. We aimed to describe more fully the
      differences observed on turning between people with and without PD, in particular
      the extent of left-right asymmetry and the correlations between turning and age,
      balance and PD severity, using a simple clinical test. METHOD: Twenty-eight
      people with PD (median age 71; median years since diagnosis eight) and 12
      controls (median age 70) performed the video-based Standing Start 180 degrees
      Turn Test. We counted turning steps (n), evaluated turn time (sec), type and
      quality (0 - 5, based on independence, ground clearance, stability, continuity
      and posture) and calculated the 95% limits of left-right agreement. RESULTS: The
      groups differed (p < 0.004) on step count (medians 4.5 vs. 3), time (2.3 sec vs.
      1.7 sec) and quality (4 vs. 5). In the PD group, 75% turned 'on-the-spot' and
      differences turning left and right were marked (e.g., 95% upper limit for step
      count 6.6). Among controls, 42% turned 'on-the-spot' and turning was symmetrical
      (e.g., 95% upper limit for step count 1.7). Step count was most closely
      correlated with self-assessed disability in PD (r = 0.67; p = 0.001) and with age
      among controls (r = 0.87; p = 0.001). CONCLUSIONS: People having difficulty
      turning are likely to have trouble with many everyday activities and thus may
      benefit from rehabilitation. Directional asymmetry in turning is easily
      identifiable and future studies should explore its diagnostic value.

PMID- 18608365
TI  - Development and psychometric properties of the Sensory Responsiveness
      Questionnaire (SRQ).
AB  - PURPOSE: Individuals with Sensory Modulation Disorder (SMD) are characterized by
      an inability to normally grade the degree, intensity and nature of their
      responses to sensory input and are limited in their ability to fully participate
      in daily life activities, and attain optimal quality of life. Most existing
      diagnostic tools are intended for paediatric populations. A questionnaire that
      assesses the intensity of the affective-emotive responsiveness of adults to
      stimuli in all sensory modalities and the frequency of such responses for
      diagnosing adults with disorders in sensory modulation is necessary. This article
      describes the development and assessment of the psychometric properties of a
      novel instrument, the Sensory Responsiveness Questionnaire (SRQ), for this
      purpose (see Appendix). METHOD: The SRQ evolved through three developmental
      phases (Pilot, Version-I, and the most recent Version-II). Each phase comprised
      several studies conducted to further refine the instrument and to examine its
      psychometric properties with adults with Sensory Modulation Disorder versus SMD
      free individuals (n=39 for the pilot version, n=399 for Version-I, and n=48 for
      Version-II). RESULTS: The scales of Version-II indicated high test-retest
      reliability, moderate criterion validity and strong significant construct
      validity. CONCLUSION: There is strong indication that the SRQ can be used to
      diagnose adults with SMD.

PMID- 18608366
TI  - Management of shoulder and proximal upper limb spasticity using botulinum toxin
      and concurrent therapy interventions: a preliminary analysis of goals and
      outcomes.
AB  - PURPOSE: To explore the role of Botulinum Toxin type A (BoNT-A) in the management
      of the spastic hemiplegic shoulder and identify the common achievable goals for
      treatment. METHOD: Set in a regional spasticity management service in the UK, a
      prospective observational cohort study was undertaken. Patients (n = 16) were
      receiving BoNT-A (Dysport) injection and concurrent therapy for spasticity of the
      shoulder girdle or proximal upper limb following stroke/other acquired brain
      injury. Mean age 54.5 (SD 15.7) years. Mean time since injury: 15.7 months.
      Functional goals for intervention were determined through agreement with the
      patient or their carers using Goal Attainment Scaling (GAS). Evaluation of
      spasticity (Modified Ashworth Scale), pain (numbered graphic rating scale) and
      three standard passive function tasks (washing, dressing and positioning) were
      also undertaken. RESULTS: Sixteen weeks post-injection, significant improvements
      were identified in spasticity (Z = -3.535, p <0.0001), pain (Z = -1.942, p =
      0.052) and passive function (Z = -3.172, p = 0.002). GAS scores had improved in
      all but one subject, with goals either achieved or over-achieved. CONCLUSIONS:
      BoNT-A injection of the proximal upper limb, with combined therapy, produced a
      reduction in spasticity, improvement in passive function and pain. Management of
      upper limb spasticity should include evaluation and, if necessary treatment, of
      the shoulder girdle and proximal musculature.

PMID- 18608367
TI  - Continuous passive motion as an adjunct to active exercises in early
      rehabilitation following total knee arthroplasty - a randomized controlled trial.
AB  - PURPOSE: Continuous passive motion is frequently used post-operatively to
      increase knee range of motion after total knee arthroplasty in spite of little
      conclusive evidence. The aim of this study was to examine whether continuous
      passive motion (CPM) as an adjunct to active exercises had any short time effects
      (after one week and three months) on pain, range of motion, timed walking and
      stair climbing. METHOD: A randomized controlled trial was conducted. A total of
      63 patients undergoing primary TKA were randomly assigned into an experimental
      group receiving CPM and active exercises and a control group receiving active
      exercises only. Outcomes were assessed by goniometer, visual analogue scale
      (VAS), timed 'Up and Go' test (TUG), timed 40 m walking distance and timed stair
      climbing. RESULTS: There were no statistical differences between the treatment
      groups for any outcome measures either at one week or after three months. For the
      whole group, a significant and 50% reduction in pain score was found after three
      months (p < 0.01). Compared with before surgery, a significantly impaired knee
      flexion range of motion (p < 0.01) and a significantly decreased number of
      patients able to climb stairs were found after three months (p < 0.01).
      CONCLUSION: CPM was not found to have an additional short-time effect compared
      with active physiotherapy. After three months considerable pain relief was
      obtained for the whole group, the patients preoperative ROM was not restored and
      the number of patients able to climb stairs had decreased.

PMID- 18608368
TI  - Surgery for chronic Achilles tendinopathy produces worse results in women.
AB  - PURPOSE: To report the middle term outcome in male and female patients who
      underwent surgery for chronic recalcitrant Achilles tendinopathy. METHODS: We
      tried to match each of the 58 female patients with a diagnosis of tendinopathy of
      the main body of the Achilles tendon with a male patient with tendinopathy of the
      main body of the Achilles tendon who was within two years of age at the time of
      operation. A match accordingly was possible for 41 female subjects. RESULTS:
      Female patients were shorter and lighter than male patients. They had similar
      BMI, lower calf circumference, similar side-to-side calf circumference
      differences, and greater subcutaneous body fat than men. Of the 41 sedentary
      patients, only 25 reported an excellent or good result. Of these, three had
      undergone a further exploration of the Achilles tendon. The remaining patients
      could not return to their normal levels of activity despite prolonged supervised
      post-operative physiotherapy, with cryotherapy, massage, ultrasound, pulsed
      magnetic, and laser therapy. CONCLUSION: Females experience more prolonged
      recovery, more complications, and a greater risk of further surgery than males
      with recalcitrant Achilles tendinopathy.

PMID- 18608369
TI  - Calcific tendinopathy of the rotator cuff. Conservative management with 434 Mhz
      local microwave diathermy (hyperthermia): a case study.
AB  - PURPOSE: To report the effects of local microwave diathermy (hyperthermia) at 434
      Mhz on calcific tendinopathy of the shoulder in two middle aged patients.
      METHODS: Two middle-aged women with calcific tendinopathy of the shoulder were
      treated with local microwave diathermy (hyperthermia) at 434 Mhz three times a
      week for four weeks. Plain radiographs and ultrasonography demonstrated calcific
      deposits in the area of infraspinatus or supraspinatus. Shoulder Pain and
      Disability Index (SPADI) and passive Range of Motion (ROM) were used to assess
      the response to treatment. RESULTS: At the end of the treatment period, the
      improvement as measured by the SPADI score was respectively 30% for the first
      patient and 40% for the second patient with an improvement of the shoulder
      passive ROM for both patients. The calcific deposits seen on the initial
      radiographs and ultrasonography were no longer visible. At 1 year follow-up, both
      patients continued to be symptom free. CONCLUSIONS: Hyperthermia is a safe option
      in the management of calcific tendinopathy of the shoulder. Prospective
      randomized controlled studies with long term assessment are needed to further
      document its therapeutic efficacy.

PMID- 18608370
TI  - Eccentric calf muscle training in athletic patients with Achilles tendinopathy.
AB  - PURPOSE: To evaluate the effects of eccentric strengthening exercises (ESE) in
      athletic patients with Achilles tendinopathy. METHODS: Forty-five athletic
      patients (29 men, average age 26 years +/- 12.8, range 18 - 42; 16 women, average
      age 28 years +/- 13.1, range 20 - 46; average height: 173 +/- 16.8, range 158 -
      191; average weight 70.8 kg +/- 15.3, range 51.4 - 100.5) with a clinical
      diagnosis of unilateral tendinopathy of the main body of the Achilles tendon
      completed the VISA-A questionnaire at first attendance and at their subsequent
      visits. The patients underwent a graded progressive eccentric calf strengthening
      exercises programme for 12 weeks. RESULTS: The mean pre-management VISA-A scores
      of 36 (SD 23.8; 95% CI: 29 - 46) improved to 52 (SD 27.5; 95% CI: 41.3 - 59.8) at
      the latest follow up (p = 0.001). Twenty seven of the 45 patients responded to
      the eccentric exercises. Of the 18 patients who did not improve with eccentric
      exercises, 5 (mean age: 33 years) improved with two peritendinous aprotinin and
      local anaesthetic injections. 10 of the 18 patients (9 men, mean age 35 years; 1
      woman aged 40 years) who did not improve with eccentric exercises and aprotinin
      injections proceeded to have surgery. The remaining three patients (3 women, mean
      age 59.6 years) of the 18 non-responders to eccentric exercises and aprotinin
      injections declined surgical intervention. CONCLUSIONS: ESE in athletic patients
      provide comparable clinical outcome compared to our previous results in non
      athletic patients. ESE are a viable option for the management of AT in athletes,
      but, in our hands, only around 60% of our athletic patients benefited from an
      intensive, heavy load eccentric heel drop exercise regimen alone. If ESE fail to
      improve the symptoms, aprotinin and local anaesthetic injections should be
      considered. Surgery is indicated in recalcitrant cases after 3 to 6 months of non
      operative management.

PMID- 18608371
TI  - Pennation angle of the soleus in patients with unilateral Achilles tendinopathy.
AB  - We measured the ultrasound scans of 23 (21 males, two females) physically active
      subjects (mean age: 40 years; range: 20 - 58) with unilateral Achilles
      tendinopathy to determine the pennation angle in the soleus muscles of the
      affected and non-affected limb. All scans were performed by one radiologist. The
      pennation angle was lower on the affected side in 15 patients, and higher on the
      non-affected side in eight patients. There was a significant difference in the
      angle of pennation of the soleus muscle on the affected side (15.9 degrees )
      compared with that on the non-affected one (17.3 degrees ; p = 0.01). Patients
      with symptomatic Achilles tendinopathy are more likely to have decreased
      pennation angle of the soleus muscle on the affected side. This may have
      implications for appropriate management of Achilles tendinopathy.

PMID- 18608372
TI  - Animal models of tendinopathy.
AB  - PURPOSE: The term tendinopathy describes non-ruptured tendon injuries. While
      several important studies have evaluated the aetiology, pathogenesis, and
      treatment of this common condition, further study is needed. Several animal
      models, which allow for full tissue evaluation on different organizational levels
      and stages of disease, have been used to investigate tendinopathy. METHOD: A
      literature review was conducted to identify and evaluate animal models that have
      been developed and used to study the aetiology and pathology of tendinopathy.
      RESULTS: Animal models of tendinopathy fit into two general categories based on
      the mode of injury application: (i) models that induce tendinopathy through a
      change in the mechanical environment, and (ii) models that induce tendinopathy
      through a chemical agent. The cost, difficulty, invasiveness, reproducibility and
      time required to induce injury in these models varies. Mechanically-induced
      models are beneficial since they induce injury through repetitive mechanical
      loading, similar to how tendinopathy is believed to develop in the human
      condition. Chemically-induced models are beneficial by allowing for the study of
      the interplay among inflammatory cells, mechanical loading and tissue healing.
      CONCLUSION: Further work is needed to fully characterize and understand
      tendinopathy. Appropriate animal models provide a greater understanding of human
      tendinopathy, leading to better prevention and treatment.

PMID- 18608373
TI  - Italian translation of the VISA-A score for tendinopathy of the main body of the
      Achilles tendon.
AB  - Purpose. To translate and adapt the English VISA-A questionnaire to Italian, to
      perform reliability and validity evaluations of the Italian VISA-A version in
      patients with tendinopathy of the main body of the Achilles tendon. Methods. The
      VISA-A English version was translated into Italian by a bilingual orthopaedic
      surgeon. The back translation of the Italian version into English was performed
      by another bilingual orthopaedic surgeon. The original version was compared with
      the back translation. The VISA-A-I questionnaire was then administered to 50 male
      athletes (average age 26.4, range 18 - 49 years) with a diagnosis of tendinopathy
      of the main body of the AT. For test-retest evaluation, the 50 patients were
      asked to complete the questionnaire at first examination, and 30 minutes
      following the end of this examination. Results. The kappa statistics for 50
      patients was 0.80 (range 0.7 - 0.86). There were no significant differences
      between the scores immediately after the consultation and 30 minutes later.
      Conclusions. Italian and the English versions of the VISA-A questionnaire
      evaluate the same aspects of clinical severity in patients with tendinopathy of
      the main body of the Achilles tendon.

PMID- 18608374
TI  - Everyday walking with Parkinson's disease: understanding personal challenges and
      strategies.
AB  - PURPOSE: This qualitative study was designed to explore the personal experience
      of everyday walking with Parkinson's disease (PD), the challenges and the
      strategies employed to compensate for difficulties, to help contextualise the
      scientific knowledge base. METHODS: Semi-structured interviews were undertaken
      with a sample of 20 people with idiopathic PD (12 male, 8 female; mean age 65
      years (range 50 - 80); mean disease duration 10 years (range 2.5 - 26). Verbatim
      interview transcripts were analyzed thematically using NUD*IST N6 qualitative
      data analysis software. RESULTS: Walking was invariably performed as an integral
      part of a purposeful activity within a specific context, termed walking 'plus',
      with challenges encountered by people with PD in three main areas: Undertaking
      tasks; negotiating environments; and making transitions to walking. The two key
      strategies to compensate for difficulties experienced were monitoring through the
      use of concentration, and correcting through generating rhythm and size of steps.
      Carers supported monitoring and correcting. CONCLUSION: People with PD need to
      constantly assess and drive their walking performance. Attentional resources,
      which can themselves be compromised in PD, were used to accomplish what is
      normally a largely automatic activity. Personal accounts support scientific
      hypotheses. Rehabilitation interventions and measurements in PD need to reflect
      both the physical and psychosocial context of everyday walking.

PMID- 18608375
TI  - Ageing of human muscles and tendons.
AB  - At whole muscle level, the reduction in intrinsic force observed with ageing is
      probably the result of the combined effect of changes in: (i) muscle
      architecture, (ii) tendon mechanical properties, (iii) neural drive (reduced
      agonist and increased antagonist muscles' activity), and (iv) single fibre
      specific tension. Only recently have alterations in muscle architecture and in
      tendon mechanical properties been shown to contribute to the reduction in
      intrinsic muscle force, and tendon stiffness changes play an important role. Of
      note is the fact that most of these changes may be reversed by 14 weeks of
      resistive training, for both fibre fascicle length and tendon stiffness were
      found to be increased by 10% and 64%, respectively. Surprisingly, however,
      training had no effect on the estimated relative length-tension properties of the
      muscle, indicating that the effects of increased tendon stiffness and increased
      fascicle length cancelled out each other. It seems that natural strategies may be
      in place to ensure that the relative operating range of muscle remains unaltered
      by changes in physical activity, and perhaps age.

PMID- 18608376
TI  - A descriptive profile of caregivers of older adults with MS and the  assistance
      they provide.
AB  - PURPOSE: To describe and compare spousal and non-spousal caregivers of older
      adults with multiple sclerosis (MS), the nature and extent of assistance they
      provide, and the challenges they experience in the course of their caregiving
      role. METHOD: This cross-sectional descriptive study uses data from telephone
      interviews with 302 caregivers of older adults with MS. Descriptive statistics,
      Chi-square and Wilcoxon tests were used to generate and compare caregiver
      profiles. A proportional odds model examined factors associated the provision of
      greater extent of care. RESULTS: Spousal and non-spousal caregivers differed in
      age, sex, location of residence, and employment status. The characteristics of
      the people with MS for whom they cared were very similar. Spousal caregivers
      assisted with more activities,although non-spousal caregivers provided equivalent
      caregiving time. Twenty percent of caregivers spent more than 3.5 h per day
      caregiving. Caregiving time was influenced by cognitive and ADL status of the
      person with MS, and the number of caregiving activities performed. Challenges
      reported by caregivers were similar. CONCLUSIONS: Both spousal and non-spousal
      caregivers of older adults with MS provide substantial assistance, and experience
      many challenges. Rehabilitation professionals need to be aware of the diversity
      of caregivers and the assistance they provide to facilitate appropriate support
      and resources.

PMID- 18608377
TI  - Tendinopathy and tendon injury: the future.
AB  - Tendon disorders are debilitating, and difficult to manage. Current management
      strategies offer symptomatic relief, but do not result in definitive disease
      resolution. Despite remodeling, the biochemical and mechanical properties of
      healed tendon tissue may never match those of intact tendons. This article
      presents a detailed up-to-date review of possible strategies for optimizing
      tendon healing and repair, such as growth factor therapy, gene therapy, and
      tissue engineering.

PMID- 18608378
TI  - Mesenchymal stem cell therapy for equine tendinopathy.
AB  - Optimal management of tendon overuse injuries in equine and human athletes should
      avoid the formation of excessive scar tissue, regenerate normal tendon matrix,
      and reduce re-injury rates. We hypothesized that the implantation of marrow
      derived stromal stem cells (BM-MSCs), in far greater numbers than are present
      normally within tendon tissue, would synthesize a matrix more closely resembling
      tendon matrix than scar tissue, and hence increase the capacity to return to
      performance successfully. This article reviews the technique used clinically in
      the horse and the current outcome data for horses treated by the autologous
      implantation of BM-MSCs into moderate to severe acute superficial digital flexor
      tendon (SDFT) injuries. Bone marrow was aspirated from the sternum under standing
      sedation. The nucleated adherent cell population (containing the BM-MSCs) were
      isolated and expanded so that, after approximately three weeks, the cells were re
      suspended in the supernatant from the bone marrow and implanted into injured SDFT
      under ultrasonographic guidance. The horses then entered a 48-week rehabilitation
      period consisting of an ascending exercise regime. By September 2006, 168
      racehorses had undergone this regimen. For horses which had returned to full
      work, 18% had re-injured, which compared favourably to previous studies on
      conventional management (56% re-injury rate). No adverse effects were noted other
      than needle tracts visible ultrasonographically. Autologous implantation of
      mesenchymal stem cells into tendon injuries may therefore improve clinical
      outcome although definitive proof of efficacy, which is still lacking, will
      require randomized controlled trials.

PMID- 18608379
TI  - What do patients feel they can do following lumbar microdiscectomy? A qualitative
      study.
AB  - PURPOSE: Lumbar microdiscectomy is becoming increasingly popular in the
      management of prolapsed intervertebral disc. The early stage of rehabilitation
      has been under-researched, with little documented about optimal activity levels
      during the initial six weeks. This study aimed to gain insight into patients'
      experiences of physiotherapy and activity choices during this period. METHOD:
      Eight participants were chosen purposively. All had undergone an uncomplicated
      lumbar microdiscectomy in the preceding six weeks in an acute neurosurgical unit
      in the Northeast of England. One-to-one semi-structured interviews were conducted
      in the participants' homes and transcribed. Data were thematically analysed
      within a constructionist framework. Mechanisms to ensure analytical rigour were
      implemented. RESULTS: Three major themes were derived inductively from the data.
      The first, 'wish for precise movement boundaries,' described participants reduced
      levels of activity postoperatively as being related to high levels of anxiety
      about the surgery and fear of re-injury. The second theme suggested that
      physiotherapy failed to help participants explore their potential for activity.
      The final theme described post-operative fatigue. CONCLUSIONS: High levels of
      postoperative anxiety about movement and activity were not addressed
      postoperatively. This has significant clinical implications and highlights the
      need for further research.

PMID- 18608380
TI  - Adiposity and tendinopathy.
AB  - PURPOSE: Tendon injuries (tendinopathy) are prevalent across the population,
      affecting active and inactive individuals and manual workers. The aetiology of
      tendinopathy is not known. However, extrinsic factors such as load are known to
      affect the prevalence. More recently, intrinsic factors have been shown to also
      affect tendons; genes, biomechanics, and strength have been shown to influence
      tendon disease. One intrinsic factor that appears to have an association with
      tendinopathy is body composition; more specifically central adiposity. Several
      studies have reported this association, and several studies have found the
      association when reporting other aspects of tendinopathy. METHOD: This paper will
      detail what is known about the association between tendinopathy and body
      composition, examine the strength of the association by evaluating studies in the
      area and speculate on potential mechanisms for the association. RESULTS: The
      association between tendon health and adiposity, especially central adiposity,
      warrants further investigation. CONCLUSION: There may be an interaction between
      adiposity and tendon pathology. Adiposity may be a key intrinsic risk factor that
      is translated into tendon disease in the presence of additional intrinsic (e.g.,
      diabetes) and extrinsic factors (e.g., load).

PMID- 18608381
TI  - Eccentric training programmes in the management of lateral elbow tendinopathy.
AB  - BACKGROUND: Eccentric training has shown promising results in the management of
      Achilles and patellar tendinopathy. Recently, studies have investigated eccentric
      training in the treatment of lateral elbow tendinopathy. PURPOSE: The purpose of
      this review was to describe eccentric training programs used to treat LET in
      order to inform clinicians and identify areas requiring further study. METHOD: An
      electronic search of publications indexed in the MEDLINE database was performed
      in May 2007. Studies comparing eccentric training with at least one other
      intervention were included. Results. Four studies investigating a total of 248
      participants were identified. Three of the four studies reported superior results
      for eccentric training compared with other interventions, although this included
      one pilot study and another study that did not include an extended follow-up.
      There were several differences between the studies, including whether eccentric
      training was painful or pain-free, the duration of eccentric training (4 - 12
      weeks) and whether training was performed in a clinical setting or at home.
      CONCLUSION: Eccentric training in the management of LET has demonstrated
      encouraging results, although the literature is limited and eccentric programs
      are varied. Future studies should investigate factors that may influence the
      outcome of eccentric training, including whether training is painful and the
      duration of eccentric training.

PMID- 18608382
TI  - Mental health in the workplace: using the ICF to model the prospective
      associations between symptoms, activities, participation and environmental
      factors.
AB  - PURPOSE: This prospective study used the framework of ICF components to
      investigate the magnitude and direction of association between body functions
      (depression/anxiety symptoms), activity (limitations in work activities),
      participation (sickness absence), and environment (psychosocial aspects) in the
      workplace setting. METHODS: A cohort of employees completed a self-report survey
      at baseline and 6 months follow-up, with analysis restricted to those with at
      least one health condition (n = 204). Self-report measures of depression/anxiety
      symptoms, limitations in work activities, sickness absences, and psychosocial
      work environment were mapped to the corresponding ICF component. The prospective
      association between these components was modelled using relative risks (RR)
      estimated from log-binomial regression. RESULTS: Depression/anxiety symptoms were
      more likely to be an outcome of other ICF components, rather than a risk factor.
      Sickness absence, limitations in work activities, and work environment all
      conferred a greater than two-fold risk of depression/anxiety symptoms 6 months
      later. CONCLUSIONS: The ICF offers a valuable approach to understanding the
      contextual influences on employee mental health and work disability. Further
      application of the ICF framework to mental health should improve the
      environmental components and encourage a wider adoption of the ICF by mental
      health researchers and practitioners.

PMID- 18608383
TI  - Achilles tendon problems: not just an orthopaedic issue.
AB  - PURPOSE: To review the current concepts on Achilles tendon involvement in various
      pathological conditions. METHOD: A literature search was conducted to trace
      relevant literature on Achilles tendon problems in general pathologies. RESULTS:
      The Achilles tendon can be involved in inflammatory and autoimmune conditions,
      genetically determined collagen abnormalities, infectious diseases, tumours, and
      neurological conditions which are not of a primary surgical nature. CONCLUSIONS:
      Although Achilles tendon problems are classically considered frequent in active
      individuals from overuse or a single acute episode, problems in the Achilles
      tendon can be a consequence of several conditions.

PMID- 18608384
TI  - Traumatic and overuse injuries of the ischial origin of the hamstrings.
AB  - PURPOSE: Both acute and chronic hamstring injuries are disabling injuries, and
      occur almost entirely to elite athletes. We report our experience in the
      management of injuries of this location. METHODS: Twenty-seven patients (29
      injuries) were included in the present study. They completed a questionnaire
      detailing their pre-injury activity, injury mechanism, rehabilitation and a
      subjective assessment of their recovery. At clinical examination, pain and hip
      motion were evaluated. RESULTS: Hamstring injuries predominantly affect males on
      the left side. Most procedures carried out were explorations with limited
      debridement and suture of the tendon. Thirty percent of patients felt they had
      returned to 100% of their pre-injury level, and 33% felt they had returned to 80 
      90% of their pre-injury level, the rest varied between less than 20% to 80%.
      Forty-five percent gave a value of zero on the visual analogue pain scale
      independent of activity. Those who gave a value above this had pain during active
      sports but not at rest. CONCLUSION: Early repair leads to acceptable recovery of
      muscle function, especially when dealing with complete avulsions. Lesions to the
      origin of the hamstring can be successfully managed if a high suspicion for the
      condition is exerted.

PMID- 18608385
TI  - Traumatic patellar tendinopathy.
AB  - PURPOSE: In patellar tendinopathy, there is anterior knee pain with tenderness of
      the attachment of the patellar tendon over the lower pole of the patella. The
      condition is commonly associated with athletic overuse, but we have encountered
      it in some patients following direct blunt trauma to the anterior aspect of the
      knee. We describe the history and management of patients with traumatic patellar
      tendinopathy. METHOD: Between April 2000 and August 2006, we managed eight
      otherwise healthy well trained athletes who developed signs and symptoms
      compatible with classical patellar tendinopathy after a direct trauma to the
      anterior aspect of the patellar tendon during sport activity. RESULTS: The
      clinical diagnosis of patellar tendinopathy was confirmed clinically and at
      imaging by MRI and ultrasound scans. Patients responded to conservative or
      surgical management, in the same way as patellar tendinopathy secondary to
      overuse. CONCLUSION: A single direct traumatic event can lead to chronic tendon
      problems. Hence, in addition to overuse injury, patellar tendinopathy can follow
      a direct trauma and exhibit the same clinical features. Further research is
      required to better understand the pathophysiology of the clinical condition.

PMID- 18608386
TI  - Cognitive level and adaptive behaviour in the Klippel-Trenaunay-Weber Syndrome.
      An example of the potentials of an early intervention model applied to a complex
      pathology.
AB  - PURPOSE: The Klippel-Trenaunay-Weber syndrome is a rare, congenital disorder
      characterized by benign excessive growth of blood vessels on the skin. Little is
      still known about its cognitive development and adaptive behaviour functioning.
      CASE STUDY: This case study describes the clinical history of a female child
      suffering from this rare syndrome and admitted to our Pediatric Unit in order to
      provide motor rehabilitation, speech therapy and psychoanalytic psychotherapy
      following an early intervention model program. After five years of treatment her
      clinical picture witnessed a considerable improvement. CONCLUSIONS: Patients with
      Klippel-Trenaunay-Weber Syndrome are best served by a multidisciplinary approach,
      and this case study shows the effectiveness of an early intervention program on
      the cognitive development and adaptive behaviour functioning.

PMID- 18608387
TI  - The circumstances of falls among people with Parkinson's disease and the use of
      Falls Diaries to facilitate reporting.
AB  - PURPOSE: Falls are common in Parkinson's disease (PD). Falls Diaries are one way
      of recording fall frequency and the surrounding circumstances; completing them
      encourages recall, and their content focuses intervention. We reviewed the
      diaries completed by people with PD during a randomized controlled trial (RCT) of
      fall prevention to ascertain the key circumstances surrounding falls. METHOD: We
      asked independently mobile, cognitively intact people with a diagnosis of PD to
      maintain a Falls Diary throughout a six-month RCT. We sent monthly diary sheets
      on which to answer questions about the 'Location', 'Fall-related activity',
      'Perceived cause', 'Landing' and 'Consequences' of every fall. We coded responses
      and counted frequencies. RESULTS: Of the 142 RCT participants (mean age 72 years;
      mean years since diagnosis 8), 135 completed the trial and their diary. We
      excluded 11 (8%) for missing data and/or unintelligible writing. The 124
      remaining diaries recorded 639 falls: 80% happened at home, commonly in bedrooms,
      living areas, kitchens and gardens. Fallers had been ambulant in 45% of events,
      standing in 32% and transferring in 21%. Six 'activity-cause combinations'
      accounted for 55% of falls (tripping 13%; freezing, festination and retropulsion
      11%; and postural instability when bending or reaching 9%, transferring 8%,
      walking 7% and washing or dressing 7%). Misjudgement and distraction played a
      part in 12% of falls described. CONCLUSIONS: Of over 600 falls surveyed, most
      happened at home, provoked by postural instability, tripping and freezing.
      Environmental adaptation and cognitive training should be trialled in falls
      prevention in PD, plus or minus traditional movement rehabilitation. Most
      participants completed Falls Diaries successfully. We advocate diary use, with
      follow-up interviews, in research and clinically. People with handwriting
      difficulty may require a typed diary, proxy diarist or interview.

PMID- 18608388
TI  - Mid-portion Achilles tendinopathy--current options for treatment.
AB  - PURPOSE: To report on the present option for management of tendinopathy of the
      main body of the Achilles tendon. BACKGROUND: Tendinopathy of the main body of
      tendo Achillis affects athletic and sedentary patients. Mechanical loading is
      thought to be a major causative factor. However, the exact mechanical loading
      conditions which cause tendinopathy are poorly defined. Repetitive mechanical
      loading induces a non-inflammatory pathology, and repetitive microtrauma
      ultimately exceeds the healing response. The management of Achilles tendinopathy
      is primarily conservative. Although many non-operative options are available, few
      have been tested under controlled conditions. This review article specifically
      focuses on eccentric training, and on shock wave therapy. Surgical intervention
      can be successful in refractory cases. However, surgery does not usually
      completely eliminate symptoms and complications are not rare. CONCLUSIONS:
      Further studies are needed to discern the optimal non-operative and surgical
      management of midsubstance Achilles tendinopathy.

PMID- 18608390
TI  - Minimally invasive stripping for chronic Achilles tendinopathy.
AB  - PURPOSE: To present a minimally invasive technique for the management of chronic
      Achilles tendinopathy (AT). METHODS: Four longitudinal skin incisions each 0.5 cm
      long are made. Two incisions are made just medial and lateral to the origin of
      the tendon; the other two incisions are made just medial and lateral to the
      distal end of the tendon close to its insertion. A mosquito is inserted in the
      incisions, and the proximal and distal portions of Achilles tendon are freed of
      all the peritendinous adhesions. A Number 1 unmounted Ethibond (Ethicon,
      Somerville, NJ) suture thread is inserted proximally, passing through the two
      proximal incisions over the anterior aspect of the Achilles tendon. The Ethibond
      is retrieved from the distal incisions, over the anterior aspect of the Achilles
      tendon. The Ethibond is slid on the tendon, which in this way is stripped and
      freed from adhesions. The procedure is repeated for the posterior aspect of the
      Achilles tendon. In addition, longitudinal percutaneous tenotomies parallel to
      the tendon fibres can be performed, if necessary. CONCLUSIONS: This technique has
      the advantages of achieving a safe and secure disruption of neo-vessels and the
      accompanying nerve supply in a minimally invasive fashion.

PMID- 18608391
TI  - Psychosocial impact of participation in the National Veterans Wheelchair Games
      and Winter Sports Clinic.
AB  - PURPOSE: The purpose of this study was to determine the characteristics of
      individuals who participate in the National Veterans Wheelchair Games (NVWG) and
      the Winter Sports Clinic (WSC) for veterans with disabilities. In addition, it
      was of interest to determine how these events had impacted their lives. METHOD:
      Participants were recruited at the 20th Winter Sports Clinic, held in Snowmass
      Colorado and the 26th National Veterans Wheelchair Games held in Anchorage,
      Alaska. Data of interest included demographic, sport participation information,
      community integration, self-esteem, and quality of life. A secondary data
      analysis was completed to determine how comparable individuals who attended the
      NVWG/WSC were to individuals who did not participate in these events. RESULTS:
      The 132 participants were a mean age of 47.4 + 13.4 and lived with a disability
      for an average of 13.4 + 12.1. Participants felt that the NVWG/WSC increased
      their knowledge of sports equipment (92%), learning sports (89%), mobility skills
      (84%), and acceptance of disability (84%). The majority of participants stated
      that the NVWG/WSC improved their life. Of those who participated at the NVWG/WSC,
      they tended to be more mobile, but have increased physical and cognitive
      limitations as measured by the CHART when compared to the non-attendees.
      CONCLUSIONS: Recommending veterans participate in events such as the NVWG and WSC
      can provide psychosocial benefits to veterans with disabilities.

PMID- 18608392
TI  - Relationships between muscular torque and gait speed in chronic hemiparetic
      subjects.
AB  - PURPOSE: To identify which paretic and non-paretic muscular groups of the lower
      limbs were the best predictors of gait speed in chronic hemiparetic subjects.
      METHOD: Twelve hemiparetic subjects with ages ranging from 65 to 75 years (70.67
      +/- 3.31 years) were included in this cross-sectional study. All participants had
      time since onset of stroke of at least six months and the ability to walk
      independently. Main outcome measures included self-selected gait speed and
      maximum isometric torques of both the paretic and non-paretic lower limbs.
      Pearson's correlation coefficients and stepwise regression analysis were employed
      to investigate the level of associations between the outcome variables. RESULTS:
      Mean gait speed was 0.65 +/- 0.33 ms(-1). There were significant differences (p <
      0.01) in torques values between paretic and non-paretic lower limbs for all
      assessed muscular groups. Stepwise regression analysis revealed that the most
      important independent variable for predicting gait speed was the isometric torque
      of paretic knee flexors ([image omitted] ). No significant associations were
      found between any torque values of the non-paretic side and gait speed.
      CONCLUSIONS: The paretic knee flexors were shown to play an important role in
      predicting gait speed after stroke, but no influences were found for the muscular
      groups of the non-paretic side. Therefore, findings of the present study suggest
      that paretic knee flexors torque should be addressed in rehabilitation programmes
      aiming to improve gait speed after stroke.

PMID- 18608393
TI  - On becoming a practitioner-researcher in remote northern Australia: personal
      commitment and resources compensate for structural deterrents to research.
AB  - AIM: This study critically explores the experience of one clinician who developed
      the practitioner-researcher role in a remote hospital. PARTICIPANT: One
      occupational therapist working in rehabilitation who had never previously done or
      been trained for research but who completed and published a randomized controlled
      trial. SETTING: Government hospital rehabilitation ward in remote northern
      Australia. METHOD: Data from a reflective journal and project records were
      content analysed using a conceptual framework of the metropolitan practitioner
      researcher experience. RESULTS: The participant's experience was similar to that
      of metropolitan practitioner-researchers as it was not just a matter of doing
      research, but rather one of role change from practitioner to researcher. The
      remote context created structural conditions that discouraged and hindered
      research and made the task of researcher role development challenging with high
      personal costs. Research deterrents included a lack of: Research-related
      infrastructure (such as information technology), research development policy,
      research accommodations in job descriptions, dedicated funding to support
      research time release and training, and research support networks. These
      deterrents were a consequence of the remote setting. Investment of substantial
      personal time, money and use of pro bono city research advisers was required to
      compensate for structural deterrents to ensure project completion. CONCLUSION:
      Researcher role development was central to project success, the remote context
      dominated role development processes and personal resources were needed to
      compensate for structural research deterrents

PMID- 18608394
TI  - Using ICF-Environment factors to enhance the continuum of outpatient ABI
      rehabilitation: an exploratory study.
AB  - PURPOSE: This study utilized the Environment dimension of the ICF, to explore
      needs of outpatients and their family members in the context of system and
      professional needs in an outpatient rehabilitation unit. METHOD: A two-phase
      qualitative exploration comprised structured workshops with outpatient
      rehabilitation unit professional staff and semi-structured interviews on two
      occasions with 18 outpatients and their significant others. Data was thematically
      analysed and categorized according to ICF Environment dimensions. RESULTS: The
      study found that the ICF Environment dimension was a worthwhile area for
      research, beneficial for outpatient professionals, relevant to patient and family
      members' concerns, and useful for conceptualizing intervention. The study found
      that key foci for outpatient assistance at the Environment level should include:
      psychosocial support and relationships; information transfer and communication in
      transition to outpatient rehabilitation; and subsequent connection with
      community, vocational and support services. CONCLUSION: Research using the ICF
      Environment dimension provides a practical means of connecting some of the
      features of a community-oriented approach with hospital or centre-based
      outpatient rehabilitation.

PMID- 18608395
TI  - The relationship between upper limb activity and impairment in post-stroke
      hemiplegia.
AB  - PURPOSE: To investigate the relationship between upper limb impairments and
      activity limitation. METHOD: A cross sectional, single assessment observational
      study in which people with hemiplegia as a result of a stroke underwent a testing
      procedure in an instrumented wrist rig in which the following measures of
      impairment were recorded: Spasticity; motor control (ability to track a moving
      target); muscle activation patterns during tracking; stiffness; range of active
      movement and isometric muscle strength. Participants also performed clinical
      tests of upper limb activity (Action Research Arm Test) and hyper-tonicity
      (Modified Ashworth Scale). RESULTS: Seventeen people with hemiplegia whose mean
      age was 57 (SD 13.4) took part. Their mean upper limb activity, measured by the
      Action Research Arm Test, was 19.3 (SD 11.2). Statistically significant positive
      relationships between level of activity and the negative features of the upper
      motor neuron syndrome such as motor control r = 0.710 (p = 0.003), active range
      of movement r = 0.540 (p = 0.025) and strength into flexion r = 0.515 (p = 0.034)
      and extension r = 0.575 (p = 0.016) were identified, but not with the positive
      features, such as spasticity or the secondary features such as stiffness.
      CONCLUSIONS: The negative features of the upper motor neuron syndrome appear more
      likely to affect upper limb activity than the positive or secondary features, but
      findings need confirming in different study populations, preferably with larger
      samples.

PMID- 18608396
TI  - Psychosocial and socio-demographic factors associated with outcomes for patients
      undergoing rehabilitation for chronic whiplash associated disorders: a pilot
      study.
AB  - PURPOSE: Identify psychosocial and socio-demographic factors (measured prior to
      treatment) that were associated with post-treatment self-perceived pain and
      disability and two secondary outcomes: psychological distress, and return to work
      in patients undergoing multidisciplinary rehabilitation for chronic whiplash
      associated disorders (WAD). METHOD: Interviews were conducted with 28 patients
      with chronic WAD at entry to and completion of an intensive rehabilitation
      program, and a telephone interview was carried out three months later.
      Participants completed pain and disability, and psychological distress
      questionnaires, at baseline and at both follow-ups. They also completed
      psychosocial questionnaires and provided socio-demographic information. The
      effect of each of the independent variables on the outcomes was first evaluated
      by simple regressions, and then subsequently by multiple regression analysis.
      RESULTS: Higher baseline pain and disability predicted higher pain and disability
      at both follow-ups (p < 0.001), and higher psychological distress at program
      completion (p = 0.003). Younger age (p = 0.028) and higher baseline psychological
      distress (p = 0.002) were associated with higher psychological distress three
      months post-rehabilitation. Greater social support at work was prognostic of
      return to work at program completion (p = 0.04). CONCLUSIONS: Baseline pain and
      disability was the only factor that affected pain and disability post
      rehabilitation. Psychosocial factors played a role in the prognosis of
      psychological distress and return to work.

PMID- 18608397
TI  - The impact of fatigue on communication in multiple sclerosis. The insider's
      perspective.
AB  - PURPOSE: The aim of this study was to investigate the relationship between
      fatigue and communication in people with MS. METHOD: A phenomenological approach
      was used in in-depth interviews with 10 people with MS to gain insight into the
      lived experience of the interaction between MS fatigue and communication. Themes
      were derived from inductive analysis of verbatim transcripts of the interviews.
      RESULTS: Participants framed their observations around three major themes. In the
      first 'revealing communication changes' an increase in the severity of
      communication symptoms and the onset of new communications symptoms when
      experiencing fatigue were reported. In the second 'concealing and coping' a range
      of covert and overt strategies employed to manage fatigue and communication
      changes were described. Finally the complex interplay between symptoms of fatigue
      and communication, strategies employed to manage these symptoms and societal
      attitudes was reported in 'barriers to participation'. CONCLUSIONS: Fatigue
      impacts on communication impairment, activity and participation. Self reports
      have an important role to play in clinical assessment of fatigue and
      communication in MS. Multidisciplinary team input is vital for the effective
      management of clients with MS fatigue and communication change. Further research
      into the impact of fatigue on different aspects of communication is required.

PMID- 18608398
TI  - Surgical management of tendinopathy of biceps femoris tendon in athletes.
AB  - PURPOSE: To report on the clinical features and results of surgical management of
      11 athletes who were operated on for tendinopathy of the tendon of the biceps
      femoris. METHODS: Eleven male athletes (average age 24.4, range 18 - 27 years)
      underwent surgery for tendinopathy of biceps femoris tendon. At surgery, if the
      tendon appeared grossly intact, with only minimal signs of adherences to the
      surrounding tissues, an extensive tenolysis and multiple longitudinal tenotomies
      were performed. If areas of tendinopathy were identified, they were excised and
      sent for histology. The tendon of the biceps femoris was sutured along the
      longitudinal tenotomy with Vicryl. If the tendon of biceps femoris was torn, the
      proximal end of the tendon received a Krackow stitch with Vicryl, and two suture
      anchors were inserted in the fibular head. The tendon of the biceps femoris was
      thus reconstructed. Functional ability was scored with the Cincinnati Knee Rating
      System. RESULTS: The Cincinnati rating system showed a statistically significant
      improvement from a preoperative average rating of 35 (range 23 to 54) to an
      average of 74 (range 62 to 80) postoperatively (p < 0.05). CONCLUSIONS: Surgery
      should be considered when well-supervised nonoperative management of biceps
      femoris tendinopathy fails. Stripping of the paratenon, removal of degenerated
      tissue, and multiple longitudinal tenotomies of the biceps femoris tendon should
      be performed. If the tendon is torn, it should be repair under appropriate
      tension, and, if necessary, reinserted on the head of the fibula.

PMID- 18608399
TI  - Back to work - a two-year outcome of a multidisciplinary rehabilitation programme
      focused on physical function and pain.
AB  - PURPOSE: To analyze why some responded positively to rehabilitation and why some
      did not. METHOD: Sixty participants with musculoskeletal disorders, mainly neck
      and back pain participated in a 7-week rehabilitation programme which was based
      on a combination of theoretical and practical education and physical activities.
      Before and after the programme and 6, 12 and 24 months after completion of the
      programme all participants were evaluated with the Disability Rating Index (DRI)
      and Pain Intensity Rating on a Visual analogue scale (VAS). RESULTS: In the
      participants who had full-time sick leave from the start of the programme to the
      2-year follow-up (Group I) self-experienced physical disability and pain ratings
      were high and showed no decrease and were maintained up until the 2-year follow
      up. For the participants who had part-time sick leave or no sick leave (Group II)
      physical disability and pain ratings were initially lower than in Group I and
      decreased gradually, (p < 0.01) and (p < 0.05), respectively throughout the 2
      year follow-up period. CONCLUSION: Participants in Group I did not benefit from
      the rehabilitation programme and did not show improvement in their physical
      disability and pain rating. Group II showed decreased physical disability and
      pain rating. The decrease was gradual and was maintained up until the 2-year
      follow-up period. These results may indicate that persons with musculoskeletal
      pain with severe disability and pain require other rehabilitation programmes than
      those with moderate symptoms. This research has highlighted the need for
      development of such programmes.

PMID- 18608400
TI  - Comparison two-year effects of once-weekly and twice-weekly water exercise on
      health-related quality of life of community-dwelling frail elderly people at a
      day-service facility.
AB  - PURPOSE: The purpose of this study was to compare two-year effects of once-weekly
      and twice-weekly water exercise programmes at a day-service facility on the
      health-related quality of life (HRQL) of frail elderly people. METHOD: This
      single blind, prospective, longitudinal randomized pilot study separated 22
      community-dwelling frail elderly people into once-weekly (once group: n = 10) and
      twice-weekly (twice group: n = 12) groups: the two-year exercise interventions
      were once- or twice-weekly 1-h sessions. Water exercise sessions comprised
      warming-up on land, activities of daily living (ADL) exercise, stretching,
      strength, and relaxation in water. The HRQL was evaluated using the Medical
      Outcomes Survey Short Form-36 questionnaire (SF-36); ADL dependence was assessed
      using the Functional Independence Measure (FIM). RESULT: Both groups showed
      significant increases over pre-intervention (pre) scores at 6 months and 12
      months on Physical Component Summary and Mental Component Summary. In the once
      group, both were lower at 24 months than at 6 months and 12 months. The FIM
      scores were significantly different from pre at 6 months and 12 months in both
      once and twice groups, and between pre and 24 month in the twice group.
      CONCLUSION: Better than once-weekly exercise, twice-weekly water exercise
      controlled deterioration of HRQL, ADL, and knee extensor muscle strength (KEX)
      with ageing.

PMID- 18608401
TI  - Outcome of multidisciplinary investigations of long-term sickness absentees.
AB  - OBJECTIVE: The aim was to investigate the results of multidisciplinary
      investigations of long-term sickness absentees regarding diagnoses, degree and
      prognoses of work incapacity, and need of rehabilitation measures and whether
      this was associated with socio-demographic factors. METHOD: A cross-sectional
      study of 545 long-term (>1 year) sickness absentees referred to multidisciplinary
      investigations by the Social Insurance Office. Data was obtained from
      questionnaires and medical records. The patients were examined by specialists in
      psychiatry, orthopaedic surgery, and rehabilitation medicine who afterwards
      agreed on diagnoses, work incapacity, time to return to work (RTW), and
      rehabilitation measures. Descriptive statistics and logistic regression were used
      for description and analyses of data. Data on age, country of birth, education,
      employment and marital status were included. RESULTS: The prevalence of
      psychiatric diagnoses was 72%, and 58% of the patients had that in combination
      with somatic diagnoses. Most patients were assessed to be capable of RTW within 6
      - 24 months after further rehabilitation measures. Higher age was associated with
      a negative prognosis of RTW and those patients were less often recommended
      additional rehabilitation. CONCLUSION: Despite long-term sickness absence and
      high rates of psychiatric and somatic diagnoses in combination, RTW was
      considered possible for most patients after further rehabilitation measures.

PMID- 18608402
TI  - Informal primary carers of stroke survivors living at home-challenges,
      satisfactions and coping: a systematic review of qualitative studies.
AB  - PURPOSE: To summarize qualitative studies from the last decade that focus on
      experiences of caring for stroke survivors and to describe challenges,
      satisfactions and coping strategies. METHODS: A systematic review of qualitative
      studies identified from English language medicine, nursing and psychology
      databases from 1996-2006 was undertaken. RESULTS: Seventeen qualitative studies
      fitting the inclusion and exclusion criteria, mostly from the USA, were
      identified. All used carer interviews. These studies corroborate the quantitative
      research, commonly describing difficulties including emotional responses,
      uncertainty and associated information and training needs. However, compared with
      quantitative research, qualitative studies provide a more detailed, complete
      picture of carers' experiences and identify additional areas including role and
      relationship changes, positive outcomes and coping strategies. CONCLUSIONS:
      Qualitative studies add significantly to our understanding of carers'
      experiences. Caring for stroke survivors is often challenging but focusing on the
      difficulties and not drawing attention to successful management strategies and
      satisfaction reported by carers, limits understanding and reduces the chances of
      providing appropriate support. Future qualitative research should consider the
      implications of the timing of collection more carefully and should move away from
      simple content or thematic analysis which tends to emphasize similarities amongst
      carers and should now focus on understanding carer diversity. Acknowledging this
      diversity should maximize the chances of providing appropriate support.

PMID- 18608403
TI  - High volume ultrasound guided injections at the interface between the patellar
      tendon and Hoffa's body are effective in chronic patellar tendinopathy: A pilot
      study.
AB  - PURPOSE: To evaluate a novel conservative management modality for patellar
      tendinopathy. METHODS: We recruited nine patients with patellar tendinopathy who
      had failed conservative management and showed evidence of neovascularisation on
      power Doppler scanning. A high volume ultrasound guided injection at the
      interface between the patellar tendon and Hoffa's body. The injection contained
      10 ml 0.5% Bupivacaine, 25 mg Hydrocortisone, and between 12 and 40 ml
      normosaline. 100 mm visual analogue scales (VAS) for pain and for function, and
      Victorian Institute of Sport Assessment - Patellar tendon (VISA-P) questionnaires
      at an average of 9 months from the injection. RESULTS: All but one patient (whose
      pain was unchanged) improved (p = 0.028). The mean improvement in function 2
      weeks after injection was 58 mm on VAS (interquartile range 27 - 88, p = 0.018).
      The mean improvement in pain 2 weeks after injection was 56 mm on a VAS scale
      (interquartile range 32 - 80, p = 0.018). At a mean follow up of 9 months, an
      improvement of 22 points from a baseline score of 46 on the VISA-P questionnaire
      (100 being normal) was established. CONCLUSION: High volume injections to
      mechanically disrupt the neovascularisation in patellar tendinopathy are helpful
      in the management of this condition. Controlled trials would be warranted to
      investigate in a more conclusive fashion this management modality.

PMID- 18608404
TI  - Prerequisites for carrying out physiotherapy and physical activity - experiences
      from adults with cerebral palsy.
AB  - PURPOSE: The aim of this study was to get a deeper understanding into how adults
      with cerebral palsy (CP) experience physiotherapy and physical activity in a
      perspective from childhood to adulthood; and how personal and environmental
      factors influence possibilities for physiotherapy and physical activity. METHOD:
      Data was collected through interviews with 22 community-living adults (35 - 68
      years) with CP, from five counties in Sweden. The questions were open-ended and
      the interviews were taped and transcribed to written language. The material was
      analysed through qualitative content analysis, a classification process resulting
      in different themes. RESULTS: The narratives from the 22 informants, based on
      experiences from childhood to adulthood, resulted in a description of
      prerequisites for carrying out physiotherapy and physical activity. Five
      different themes were identified: (i) Being enjoyable, (ii) Giving effects, (iii)
      Being comprehensible, (iv) Being integrated in daily life, and (v) Supportive
      healthcare with competent professionals. CONCLUSION: The information from the
      interviews elucidates the importance of a lifelong support from healthcare
      professionals. Physiotherapists with attentiveness to different life situations
      in combination with good understanding and knowledge in CP could facilitate
      continuous physical activity in people growing up and ageing with CP.

PMID- 18608405
TI  - Conservative, open or percutaneous repair for acute rupture of the Achilles
      tendon.
AB  - PURPOSE: To review the complications and recovery of patients with Achilles
      tendon rupture managed by percutaneous repair, open repair, and non-operative
      means in a tertiary referral centre between 2001 and 2003. METHODS: The operating
      theatre register and logbooks of the Consultants were used to identify surgically
      managed patients, while plaster room records were used for conservatively managed
      patients. We collated demographic and management details. RESULTS: The number of
      plaster changes (p < 0.001), median length of time in cast (p < 0.001), and
      number of outpatient visits (p < 0.05) was greater in conservatively managed
      patients. We performed no formal statistical analysis given the small numbers.
      Conservative management was the least expensive and open surgery the most costly
      modality of management. Percutaneous surgery was approximately a third of the
      cost of open surgery when performed under local anaesthetic. CONCLUSION: In our
      setting, percutaneous repair and conservative management are viable alternatives
      to open surgery, which carries higher complications rates and was the most costly
      of the three. Individual patients will have different needs due to their age,
      occupation, or level of sporting activity.

PMID- 18608407
TI  - Referral of people with osteoarthritis to self-management programmes: barriers
      and enablers identified by general practitioners.
AB  - PURPOSE: We conducted a qualitative descriptive study involving general
      practitioners (GPs) in Victoria, Australia, to examine the barriers to, and
      drivers of, referral of patients with osteoarthritis (OA) to self-management
      programmes. METHOD: Participating GPs were asked to respond to a series of open
      ended questions regarding their referral of patients with OA to self-management
      programmes and their perception of the advantages and disadvantages of these
      programmes for people with OA. Interviews were audio-taped, transcribed verbatim,
      and analysed to identify primary themes in the data. RESULTS: Results suggest
      current referral of OA patients to self-management programmes from within general
      practice is influenced by GP-related factors, patient-related factors, and
      programme-related factors. A major barrier to referral was GPs limited knowledge
      about the availability of local programmes and the types of services these
      programmes provide to people with OA. Some GPs felt OA is less conducive to self
      management interventions compared to other chronic conditions (e.g., diabetes,
      asthma) and questioned the clinical benefit of programmes for people with OA.
      Enablers of GP referral included GP knowledge about content and availability of
      programmes, positive GP attitudes towards patient involvement in these
      programmes, and patient awareness of the value and availability of these
      programmes (i.e., patient-mediated referral). CONCLUSION: This study suggests
      multiple barriers and drivers of referral of patients with OA to self-management
      programmes that could be targeted in the future in order to increase referral to,
      and uptake of, these programmes in general practice.

PMID- 18608409
TI  - Life satisfaction in patients with long-term non-malignant pain-relation to
      demographic factors and pain intensity.
AB  - PURPOSE: Life satisfaction can be defined as a measure of a patient's perception
      of the difference between his reality and his needs or wants. Here we compare
      life satisfaction in patients with long-term pain to a reference group sampled
      from the normal population, and relate the results to pain intensity and to
      demographic factors. METHOD: Questionnaires containing the Life satisfaction
      (LiSat-11) checklist, a visual analogue scale (VAS) for pain, and questions on
      demographic background. RESULTS: The prevalence of responders with low level of
      life satisfaction was larger among the patients than in the reference group. In
      particular, patients born outside Northern Europe scored significantly lower than
      patients born in Northern Europe in many of the LiSat-11 domains. Pain intensity
      did not correlate well to the level of life satisfaction, except for weak
      negative correlations to satisfaction with physical health and with financial
      situation. CONCLUSION: Long-term pain is strongly associated with low life
      satisfaction. In order to increase life satisfaction, interventions related to
      social factors seem to be important.

PMID- 18608410
TI  - Cognitive complaints, neuropsychological performance and affective disorders in
      elderly community residents.
AB  - BACKGROUND: Previous studies have assessed the relationship between subjective
      cognitive complaints and objective impairment. While some of them found that
      cognitive complaints were explained by affective disorders, other researches
      found a relationship between cognitive complaints and neuropsychological
      performance. Most of them focused on memory functioning. However, elderly normal
      adults also display a decline in executive functions. This study aimed to assess
      the relationship between cognitive complaints, objective memory and executive
      performance and affective disorders. METHODS: This study was carried out with 937
      community-dwelling elderly individuals recruited from the electoral list of the
      city of Saint-Etienne, France. Cognitive complaints were assessed using the
      MacNair scale. Cognitive performances were measured via a large battery of memory
      and executive-performance tests chosen for their capacity to detect subtle
      cognitive impairment. Anxiety and depressive symptoms were assessed using scales
      devised by Pichot and Goldberg. RESULTS: Cognitive complaints were associated
      with lower scores on verbal-memory tests and several executive-performance tests.
      Moreover, affective disorders were related to some of the executive-performance
      test scores, but they were not related to scores on the Free and Cued Selective
      Reminding Test, Digit Symbol Substitution Test and Trail Making B scores.
      CONCLUSIONS: Cognitive complaints of the elderly can reflect objective memory and
      executive-performance impairments, independent of affective disorders. Cognitive
      complaints should be assessed using both memory and executive-performance tests.

PMID- 18608411
TI  - An empirical analysis on the incidence of part-time work among women with
      disabilities.
AB  - PURPOSE: To analyse the determinants of part-time employment and examine the
      impact of having a disability on the probability of working part-time. Our
      dataset allows us to take into account the heterogeneity within the disabled
      collective and identify the incidence of part-time work, for example, by type of
      disability and compare the results obtained. METHOD: Using data from the ad hoc
      module on disability of the Spanish Labour Force Survey 2002 (which contains
      detailed information on key characteristics of disabled population), we used a
      bivariate probit model to estimate the probability of disabled women working part
      time and of being employed. RESULTS: The results show that disabled women have a
      higher probability of working part-time as compared to non-disabled women,
      especially those with progressive illnesses, digestive and stomach disorders and
      chest or breathing problems. In addition, there is a positive relationship
      between longer disability durations and levels of part-time employment.
      CONCLUSIONS: Part-time employment can be used as a means to increase the levels
      of employment of disabled women, especially for those who face important barriers
      and difficulties as they try to enter into the labour market (e.g., those with
      epilepsy, mental, emotional conditions and other progressive illnesses or having
      long-term disabilities).

PMID- 18608413
TI  - Exercise on prescription schemes for stroke patients post-discharge from
      physiotherapy.
AB  - PURPOSE: 'Exercise on prescription' (EoP) schemes run by fitness instructors in
      leisure centres in the UK have potential to promote continued rehabilitation and
      activity engagement post-discharge from stroke physiotherapy. This study explores
      the views of physiotherapists, stroke patients and fitness instructors about the
      appropriateness and acceptability of EoP schemes for stroke patients post
      discharge from physiotherapy. METHOD: This qualitative study collected data from
      stroke patients referred to EoP, fitness instructors and referring
      physiotherapists (n = 30). Data were transcribed and analysed thematically.
      Exploration of key themes within and between groups was made. RESULTS: Referral
      to EoP appears to alleviate some of the distress that patients and
      physiotherapists experience at physiotherapy discharge and provide an opportunity
      for physiotherapists to wean patients from physiotherapy. However, concerns about
      risks to patients because of fitness instructors' low levels of knowledge about
      stroke and the limited monitoring of exercisers were identified. Physiotherapists
      are likely to refer only the most able patients post-stroke to EoP. CONCLUSIONS:
      The study indicates that, in the light of limited health resources, EoP schemes
      have potential benefit for people post-discharge from physiotherapy. However,
      safety needs and the concerns of stroke survivors must be considered in EoP
      scheme development and management if they are to successfully help more people
      post-stroke maintain healthy levels of activity and fitness.

PMID- 18608412
TI  - Factors associated with retirement-related job lock in older workers with recent
      occupational injury.
AB  - PURPOSES: Job lock (inability to leave a job due to financial or benefits needs)
      has been found to significantly restrict job mobility. However, it has not been
      studied in terms of inability to retire. This study evaluated the relationship
      between health, work environment, and retirement-related job lock in workers > or
      =55 with recent occupational injuries. METHODS: Workers completed a mailed, self
      report survey about their pre- and post-injury health and functioning, work
      environment, and retirement plans. Bivariate and multivariate analyses determined
      those factors associated with retirement-related job lock. RESULTS: Over half of
      the respondents wanted to retire but could not because they needed job-related
      income or benefits. Factors associated with retirement-related job lock were
      indicative of poorer health and mental function and dissatisfaction with the
      workplace social environment. No injury-related factors were significant.
      CONCLUSIONS: Retirement-related job lock was common in older workers with
      occupational injuries, and appears to be primarily due to difficulties at work,
      combined with health conditions that may impair work abilities. Workers wishing
      to retire but unable to do so may be at risk for work-related injuries, as well
      as decrements in work function and premature retirement resulting in insufficient
      income and health benefits.

PMID- 18608414
TI  - Does a cognitive-training programme improve the performance of middle-aged
      employees undergoing in-patient psychosomatic treatment?
AB  - PURPOSE: With the ever-increasing average life expectancy and rising age of
      retirement, cognitive and work capacities in advanced age take on great
      importance. Cognitive impairments, however, increase with age. The effect of
      cognitive-training programmes on people with mild cognitive impairment has not
      been verified in any systematic investigations. METHOD: This study presents a
      cognitive-training programme designed for middle-aged employees that was
      implemented and evaluated at the Psychosomatic Clinic Bad Neustadt/Saale in an AB
      study design (A: no intervention; B: intervention). RESULTS: Memory performance
      of the intervention group (n = 33) improved significantly between intake and
      discharge, compared with that of the control group (n = 40), as did self-ratings
      of memory and work-related attitudes. CONCLUSIONS: A cognitive-training programme
      is useful and effective in patients with mild cognitive impairment. Future
      studies should investigate how older or more severely impaired patients benefit
      from such a programme.

PMID- 18608415
TI  - Statistical reviewing for disability and rehabilitation.
AB  - PURPOSE: The general problem of 'getting past the statistical referee' has been
      recognised in many journals over a long period of time. The purpose of this
      article is to help authors in the review process, and to give the journal better
      statistical credentials. METHOD: This is a reflection of 20 years of statistical
      reviewing for this and other journals, calling on the literature where
      appropriate. RESULTS: A number of criteria are listed that any statistician would
      expect authors to address. The statistician should not expect a statistical
      masterclass of all of them, but a recognition of the general problems posed.
      CONCLUSIONS: By using these criteria authors should be better equipped to deal
      with statistical issues that might arise.

PMID- 18608416
TI  - Relation between post-stroke satisfaction with time use, perceived social support
      and depressive symptoms.
AB  - PURPOSE: To determine if perceived level of social support and number of
      depressive symptoms differentiates those who are satisfied with their time use
      post-stroke from those who are dissatisfied. METHOD: Secondary analysis of data
      of 54 subjects grouped by yes/no responses to 'Are you satisfied with how you
      spend your time?' Perceived social support and number of depressive symptoms were
      evaluated using the MOS Social Support Scale and Geriatric Depression Scale
      respectively. RESULTS: Time use satisfaction was high (64.8%). Dissatisfied
      subjects reported lower affectionate support and fewer positive social
      interactions (t < -2.70, p < 0.009) as well as higher levels of depression (t =
      2.06, p = 0.05). Dissatisfied subjects were more likely to endorse only three
      Geriatric Depression Scale items (i.e., 'dropped activities', 'often bored', and
      'often felt helpless') (chi2(1) > 7.27, p < 0.007). CONCLUSIONS: Persons post
      stroke who are dissatisfied with their time use may not be depressed but may
      benefit from participation in meaningful social occupations.

PMID- 18608418
TI  - Towards an ICF-based clinical measure of functioning in people with ankylosing
      spondylitis: a methodological exploration.
AB  - OBJECTIVE: To explore whether it is possible to construct clinical measures of
      functioning for patients with ankylosing spondylitis (AS) by integrating
      information obtained across categories of the International Classification of
      Functioning, Disability and Health (ICF). METHODS: Sixty-eight ICF categories
      that were identified as relevant by patients with AS and that covered body
      functions, structures, and activity and participation were analysed based on the
      Rasch model for ordered response options. The following properties were studied:
      unidimensionality, reliability, fit of the ICF categories to the Rasch model, the
      appropriateness of the order of the response options of the ICF qualifier, and
      the targeting between the ICF categories and the person's abilities. RESULTS:
      After accounting for disordered thresholds and misfitting ICF categories, a
      clinical measure of functioning for AS was proposed that contained 64 ICF
      categories. On the basis of a transformation table, the raw scores obtained by
      adding the answers to the 64 ICF categories can be transformed to the Rasch logit
      scale and to a meaningful interval scale ranging from zero to 100. CONCLUSION:
      For the first time, it has been shown that clinical measures of functioning, in
      principle, can be constructed based on the comprehensive ICF framework covering
      body functions and structures and activities and participation domains. The
      results of this investigation are preliminary and must be validated, but they are
      promising and can contribute to the acceptance and usefulness of the ICF in
      clinical practice.

PMID- 18608419
TI  - Psychological determinants of quality of life in patients with whiplash
      associated disorders-a prospective study.
AB  - PURPOSE: To evaluate whether psychological factors and personality traits
      influence recovery in terms of quality of life in patients with subacute whiplash
      associated disorders (WAD). METHOD: The data was obtained from a randomized
      controlled trial (RCT) on 47 patients. The patients completed measures of pain
      intensity, affective dimension of pain, pain location, psychological stress,
      heightened somatic awareness, depression, catastrophizing, self-efficacy, fear of
      movement (re)injury, and physical disability. After three months of physiotherapy
      interventions, the outcome of quality of life was measured with the Short Form
      Health survey (SF-12). All variables were entered in a multiple regression
      analysis, after controlling for age and sex. RESULTS: Forty patients (85%)
      completed the trial. The self-efficacy scale (SES) was the only variable in the
      model that significantly explained the fraction of the SF12-score. The
      correlation between the SES and SF-12 was B = 0.64 (p < 0.01), and the adjusted
      R(2) was 0.40 (p < 0.05), which means that 40% of the variation in the SF12
      outcomes was explained by the SES. CONCLUSION: In order to improve health-related
      quality of life in patients with WAD, the present study stresses the importance
      of targeting self-efficacy. A special effort should be made to enhance these
      beliefs in the rehabilitation process.

PMID- 18608420
TI  - A peer-led HIV counselling and testing programme for the deaf in Kenya.
AB  - PURPOSE: To describe and evaluate the establishment of the first VCT services for
      the Deaf in Africa. METHOD: Operational research methods were used to document
      programme establishment. The demographics of deaf VCT clients were compared with
      hearing clients at the same sites as well as where clients had learned of the
      service, HIV risks, and HIV test results. Univariate and multivariate analyses
      were used. RESULTS: During the two year period (January 2004 to December 2005)
      1709 Deaf and 1649 hearing clients were seen at three Deaf VCT sites. The
      majority of Deaf clients in this sample learned of the services through the peer
      education programme. Data indicate that Deaf VCT clients are as much at risk of
      HIV from sexual transmission as their hearing counterparts and that Deaf persons
      seeking VCT services have an HIV prevalence of 7%, similar to the national rate
      of 6.7%. CONCLUSIONS: The Deaf in Kenya are at risk of HIV and there is an urgent
      need for Deaf-friendly HIV services, supplemented by peer education programmes.
      This is the first published report describing HIV services run by the Deaf for
      the Deaf in the developing world.

PMID- 18608421
TI  - Prolonged benefit in post-polio syndrome from comprehensive rehabilitation: a
      pilot study.
AB  - PURPOSE: To report physical, psychological and functional outcomes from a pilot
      study of a multi-disciplinary rehabilitation programme for post-polio syndrome
      (PPS). METHOD: Twenty-seven participants completed the nine-day programme and
      were available for re-assessment at three and six months. Physical outcome
      measures were muscle strength and endurance; psychological outcomes included
      illness perceptions (IPQ), depression and anxiety (HADS); functional outcomes
      were fatigue (HFS) and client-centred occupational performance and satisfaction
      (COPM). RESULTS: There was no significant change at six months for muscle
      strength or anxiety. Significant improvements were recorded for exercise
      endurance, depression and levels of fatigue. A shift towards an endorsement that
      the patient's own behaviour could be important in symptom severity of PPS was
      seen. Five out of 24 participants demonstrated significant clinical changes in
      occupational performance and satisfaction on the COPM. CONCLUSIONS: Prolonged
      benefits were found for physical, psychological and functional outcomes. A
      qualitative study is planned to investigate the patient-reported benefits of
      attending the programme such as the support gained interacting with others with
      similar disability and in lifestyle adjustment such as pacing of physical
      activities.

PMID- 18608422
TI  - Do physical disabilities affect self-perceived quality of life in adolescents?
AB  - PURPOSE: We examined to what extent physical disabilities (PD) affect self
      perceived quality of life (QOL) among adolescents. METHOD: A survey was conducted
      on 157 adolescents (aged 15.6 +/- 1.6 years) with PD, who were attending high
      schools in Taiwan; 855 students (15.3 +/- 1.6 years) from the same geographic
      regions and without a disability were recruited as controls. The Student Version
      of the Comprehensive Quality of Life Scale (COMQOL-S) was used to assess their
      subjective and objective well-being. RESULTS: No significant differences in
      overall objective QOL score were found between the two groups but the PD group
      was poorer in health and material well-being. Adolescents with PD scored
      significantly higher in overall subjective QOL and all the seven domains
      examined. Stratified analysis showed that older students and female students with
      PD had lower life satisfaction in some domains. There were no significant
      differences in overall objective (62.1 +/- 8.3 vs. 60.9 +/- 6.4; p = 0.55) or
      subjective (72.3 +/- 12.6 vs. 74.4 +/- 13.6; p = 0.15) QOL between students in
      mainstream and special schools. CONCLUSIONS: With national health care and
      educational coverage, the QOL of adolescents with PD in Taiwan do not seem to be
      affected by the disabilities, regardless of whether they are in mainstream or
      special schools. However, the negative effect of PD on QOL becomes a concern with
      increasing age; females with PD also appear to have a lower subjective QOL in
      health and emotion.

PMID- 18608423
TI  - Disability in end-stage knee osteoarthritis.
AB  - OBJECTIVE: To examine the attributes of disability in end-stage knee
      osteoarthritis (OA) by analyzing the relationships between self-reported
      disability and objectively measured physical function after controlling pain,
      personal characteristic factors, and pathophysiological factors. METHODS: The
      present study adopted a cross-sectional design. The subjects (n=88, aged 60-80
      years) were scheduled for primary unilateral total knee arthroplasty (TKA) due to
      knee OA. Self-reported disability and pain were measured with the Western Ontario
      and McMaster Universities OA Index (WOMAC) and the RAND 36-item Health Survey 1.0
      (RAND-36). Physical performance tests included a 15-m walk test and stair
      performance. Knee isometric muscle strength was measured. A clinical examination
      included analyses of comorbidity, body mass index (BMI), and a detailed knee
      examination: The flexion range of motion (ROM) was measured; the presence of
      varus/valgus malalignments and antero-posterior laxity was assessed. Radiographs
      were analyzed with the Kellgren-Lawrence grading scale. RESULTS: In the linear
      regression model the WOMAC pain score, antero-posterior laxity of the knee, age,
      and BMI accounted for 54.8% of the variance in the WOMAC function score. In the
      bivariate analyses the WOMAC function score had a positive correlation with the
      15-m walk (r(s)=0.32, p=0.003), stairs up (r(s)=0.40, p=0.001), and stairs down
      (r(s)=0.38, p=0.001) tests, and a negative correlation with RPT extension (r(s)=
      0.45, p < 0.001) and RPT flexion (r(s)=-0.39, p=0.001) of the affected side and
      RPT flexion (r(s)=-0.39, p <0.001) of the contralateral side. The results of the
      physical performance tests also correlated with the RAND-36 Physical function
      (PF) score. Comorbid diseases and pain deteriorated the results of the physical
      performance tests and self-reported disability. Female gender deteriorated the
      results of the physical performance tests and the RAND-36 PF, but not the WOMAC
      function score. Malalignments, restriction in the flexion ROM of the knee, and
      the radiologic severity of knee OA did not affect self-reported disability.
      CONCLUSION: Pain, BMI, and antero-posterior laxity of the knee joint were major
      attributes of self-reported disability. The negative effect of comorbid diseases
      and female gender on health-related quality of life was significant. The results
      of objectively measured physical performance tests correlated with self-reported
      disability.

PMID- 18608424
TI  - Identification of quasi-in-need-of-care state (QUINOCS) among community dwelling
      elderly people using a seven-item subset of the Functional Independence Measure
      (FIM).
AB  - PURPOSE: To develop a screening test to identify community dwelling elderly
      people who are in need of assistive care but whose activities of daily living
      (ADLs) can be improved by appropriate rehabilitation intervention, so-called
      'quasi-in-need-of-care state (QUINOCS)'. METHOD: A total of 32 persons (mean age
      77.3 years) from the metropolitan area and 51 persons (mean age 82.7 years) from
      a rural area were enrolled. Two physiatrists examined them and judged whether
      they could benefit from rehabilitation intervention while visiting nurses
      evaluated their ADLs using the Functional Independence Measure (FIM). A screening
      test to identify the QUINOCS was created using a seven-item subset score of the
      FIM (feeding, bathing, dressing lower-body, bladder management, bed/chair/wheel
      chair transfer, walking/wheel chair, stairs). RESULTS: Fourteen in the
      metropolitan and 19 in the rural inhabitants were judged as the QUINOCS by the
      physiatrists. Persons whose subset scores included or ran across the intermediate
      range of independent levels (scores 3 and 4 of the FIM) showed tendency to be
      judged suitable for rehabilitation intervention. This finding was applied for
      screening algorism to identify the QUINOCS. Sensitivity and specificity of this
      test were 0.71 and 0.78 for the metropolitan, and 0.74 and 0.78 for the rural
      groups, respectively. CONCLUSION: The screening method using the 7-item subset of
      the FIM can be used for identification of the QUINOCS among elderly people
      efficiently.

PMID- 18608425
TI  - Rehabilitation of adults with dyspraxia: health professionals learning from
      patients.
AB  - PURPOSE: This study aimed to explore the experience of adults with dyspraxia,
      after discharge from inpatient care, in the course of their everyday activities.
      METHOD: A small-scale qualitative study conducted in metropolitan New Zealand
      with men who had dyspraxia after a stroke. Data collection included individual
      interviews and videoing each participant performing one or two everyday tasks
      they selected as showing the impact of the disorder. Analysis was guided by
      phenomenology. RESULTS: Analysis of the data revealed the struggle participants
      have with their unknowing and unwilling bodies, puzzled thinking, unfamiliar
      surroundings and unhandy tools. Despite the enormity of their struggles,
      participants persevere; using strategies they devise themselves to overcome
      obstacles. CONCLUSIONS: The path to recovery remains unclear as dyspraxia makes
      itself known one day and not the next. Sheer determination and a hope for the
      future helps participants continue to try to reclaim the person they were prior
      to the dyspraxia. Health professionals can help by understanding what people with
      dyspraxia experience, supporting their hopefulness of improvement and building up
      knowledge of the functional and compensatory strategies they devise to support
      participation in daily activities.

PMID- 18608426
TI  - Muscle strength, aerobic capacity and physical activity in independent ambulating
      children with lumbosacral spina bifida.
AB  - PURPOSE: This cross-sectional study investigates deficits and associations in
      muscle strength, 6-minute walking distance (6MWD), aerobic capacity (VO(2peak)),
      and physical activity (PA) in independent ambulatory children with lumbosacral
      spina bifida. METHOD: Twenty-tree children participated (13 boys, 10 girls). Mean
      age (SD): 10.4 (+/-3.1) years. Muscle strength (manual muscle testing and hand
      held dynamometry), 6MWD, VO(2peak) (maximal exercise test on a treadmill), and PA
      (quantity and energy expenditure [EE]), were measured and compared with aged
      matched reference values. RESULTS: Strength of upper and lower extremity muscles,
      and VO(2peak) were significantly lower compared to reference values. Mean Z
      scores ranged from -1.2 to -2.9 for muscle strength, and from -1.7 to -4.1 for
      VO2peak. EE ranged from 73 - 84% of predicted EE. 6MWD was significantly
      associated with muscle strength of hip abductors and foot dorsal flexors.
      VO(2peak) was significantly associated with strength of hip flexors, hip
      abductors, knee extensors, foot dorsal flexors, and calf muscles. CONCLUSIONS:
      These children have significantly reduced muscle strength, 6MWD, VO(2peak) and
      lower levels of PA, compared to reference values. VO(2peak) and 6MWD were
      significantly associated with muscle strength, especially with hip abductor and
      ankle muscles. Therefore, even in independent ambulating children training on
      endurance and muscle strength seems indicated.

PMID- 18608427
TI  - Influence of adapted sport on quality of life: perceptions of athletes with
      cerebral palsy.
AB  - PURPOSE: This study sought to examine the effect of adaptive sports participation
      on athletic identity and influence on quality of life (QOL) for individuals with
      cerebral palsy (CP) participating in the CP World Games. METHOD: Surveys were
      conducted with 73 international athletes competing in the 2005 CP World
      Championships. The survey included descriptive questions about sport involvement
      and socio-demographics, the Athletic Identity Measurement Scale, and the
      Influence on Quality of Life Scale. RESULTS: A significant relationship was found
      between influence on QOL and athletic identity (r = 0.505; p < 0.001). There was
      a moderate negative correlation between influence of adaptive sport on QOL and
      severity of disability (r = -0.264, p < 0.05). The majority of the sample either
      agreed or strongly agreed that adaptive sport positively influenced their overall
      health (84.9%) quality of life (80.8%), quality of family life (53.4%), and
      quality of social life (56.1%). Athletic identity (beta = 0.54) was the strongest
      predictor of influence on QOL with severity of disability (beta = -0.29) also a
      significant contributor. These athletes also had significantly higher mean AIMS
      scores when compared to collegiate non-athletes, collegiate recreational
      athletes, and recreational athletes with disabilities. CONCLUSIONS: The results
      suggest that participation in adapted sport is related to QOL and athletic
      identity for individuals with CP. To foster these benefits advocates for persons
      with disabilities should work toward increasing opportunities to compete in
      sports.

PMID- 18608428
TI  - Helping persons with mild or moderate Alzheimer's disease recapture basic daily
      activities through the use of an instruction strategy.
AB  - PURPOSE: The present three pilot studies assessed the effectiveness of verbal
      instructions, presented automatically through simple technology, in helping
      persons with mild-to-moderate Alzheimer's disease recapture basic daily
      activities. The activities were morning bathroom routine, dressing, and table
      setting. METHOD: The studies that focused on morning bathroom routine and on
      table-setting included three participants each, while the study that focused on
      dressing involved four participants. A non-concurrent multiple baseline design
      across participants was used for each study. The instructions and technology were
      available only during the intervention phases. RESULTS: Data showed that the
      intervention strategy involving verbal instructions for the single activity steps
      presented automatically through technology was effective in helping all
      participants on each of the activities. The participants' mean percentages of
      correct steps across activities raised from 13 - 54 during the baseline periods
      to above 80 or 90 during the intervention periods. CONCLUSIONS: The results
      suggest that the intervention strategy reported may represent a suitable approach
      for helping persons with mild or moderate Alzheimer's disease to recapture basic
      daily activities. New research should target other activities and check
      maintenance and generalization issues.

PMID- 18608429
TI  - Phantom sensations in people with complete spinal cord lesions: a grounded theory
      perspective.
AB  - PURPOSE: Phantom sensations are somatic phenomena arising from denervated parts
      of the body. There is very little research, and much diagnostic confusion,
      regarding such experiences in people with spinal cord injuries. In the case of
      'complete' spinal cord lesions, phantom experiences may challenge, and indeed,
      contradict, the understanding that both clinicians and patients have of such
      injuries. This paper seeks to provide a better understanding of such 'phantom'
      sensations in spinal cord injury. METHOD: We used grounded theory methods to
      explore 'phantom' sensations as experienced by individuals with complete (ASIA A)
      spinal lesions. Eight people with complete lesions, who were selected through
      theoretical sampling, participated in a semi-structured interview. RESULTS:
      Emergent themes included injury context, sensations experienced, the meaning of
      sensations, body connectivity, attitude and communication about sensations.
      CONCLUSIONS: Our results provide an enhanced understanding of the embodied
      experience of phantom sensations, and important insights regarding self
      construction and rehabilitative processes in people with spinal cord injury who
      experience such anomalous sensations.

PMID- 18608430
TI  - Validation of the modified assessment of living skills and resources, an IADL
      measure for older people.
AB  - PURPOSE: The aim of this study was to examine the validity of the assessment of
      living skills and resources (ALSAR) and the extent it contributes to and reflects
      the risk and accomplishment in instrumental activities of daily life for older
      people. METHOD: The assessment was examined for evidence of construct validity,
      internal, consistency and effectiveness of the categorical rating schema. Rasch
      modelling was used to examine the hierarchy of items, item performance and scale
      quality. RESULTS: A revised 5-level rating schema is proposed whereby skill
      rating levels are incrementally more at risk when a resource issue is identified.
      The sample comprised 290 ratings from 160 people 56-101 years (mean 79+/-9). Item
      mean infit statistics were 0.98 (Z = -0.2, SD = 0.63) and mean outfit statistics
      1.02 (Z = -1.0, SD = 0.74). Reliability was 0.89 with a separation index of 2.81.
      People with long standing severe vision loss display an atypical response pattern
      denoting the vision item was of low relevance to their total IADL functioning.
      CONCLUSIONS: This study has further verified the validity of the ALSAR as an IADL
      outcome measure for use with older people and has offered a more effective
      refinement of the rating scale. We note the importance of assessing vision prior
      to IADL testing.

PMID- 18608431
TI  - Predicting recovery of dextrous hand function in acute stroke.
AB  - PURPOSE: To determine the clinical characteristics during acute stroke that
      predicted dextrous function in the paretic hand at 6 months post-stroke. METHOD:
      Fifty-seven patients within 5 days post-stroke were recruited in stroke wards.
      Recovery of dextrous hand function, indicated by a score of > or =35 of Action
      Research Arm Test, was assessed weekly in the first 4 weeks then monthly till 6
      months post-stroke. The seven predictor candidates evaluated included side and
      site of brain infarct, stroke severity, cognition, spatial neglect, two-point
      discrimination (2-PD), muscle tone and muscle strength of the paretic upper
      extremity (UE). RESULTS: Site of infarct, stroke severity, 2-PD and UE muscle
      strength had independent association with dextrous hand function at 6 months post
      stroke. Stepwise multiple logistic regressions showed that the best early
      predictor was 2-PD in week 1 to 3 (Odds ratio [OR] ranged from 0.51-0.83) and UE
      muscle strength during the first 2 months post-stroke (OR > or = 1.04). The
      strongest predictor was muscle strength at week 4 post-stroke, followed by
      combined 2-PD and muscle strength at week 2 post-stroke. CONCLUSIONS: Muscle
      strength and 2-PD in the paretic UE during the first month post-stroke were the
      best predictors of dextrous hand function recovery at 6 months.

PMID- 18608432
TI  - Novel approaches to tendinopathy.
AB  - PURPOSE: The last decade has seen an evolution in the thinking of tendinopathy
      from inflammatory to degenerative and hence a change in approaches to treatment.
      METHOD: We review the literature in this field to highlight the possibility of
      neural and neural-induced inflammation in this field. RESULTS: Neuropathy is a
      possible source of pain in tendinopathy. CONCLUSION: Further work is required to
      develop the neuropathic model of tendinopathy, and to determine whether these
      neuropathic factors are responsible. The concept of neoneurovascularization being
      the issue in tendinopathy is established. The underlying mechanisms for the
      process require further evaluation.

PMID- 18608433
TI  - Reliability and validity of the modified functional reach test at the sub-acute
      stage post-stroke.
AB  - OBJECTIVES: The first aim of this study was to evaluate the within-session
      reliability of sitting balance measures by assessing forward and lateral reach
      while sitting in both healthy subjects and patients post- stroke. The second aim
      was to evaluate the ability to document change in reaching while sitting over
      time in patients post-stroke. The third aim was to compare sitting balance
      results by the modified functional reach test (MFRT) to the Balance Master (BM),
      motor and function assessments. DESIGN: Data were collected on two occasions: Two
      to three weeks post-event and again six weeks later. On each occasion within
      session reliability was tested using the intra-class correlations (ICC). The
      tests were performed three times; the second and third attempts were compared in
      order to test the within-session reliability. For assessing the concurrent
      validity, the MFRT results were compared with the BM results, Stroke Assessment
      Scale (SAS) and the Functional Independence Measure (FIM) score using Pearson
      correlations. SETTING: In-patient rehabilitation department. PARTICIPANTS:
      Patients after a first ischemic stroke 14 - 21 days post-event were recruited
      from the inpatient rehabilitation department at Hadassah University Hospital,
      Jerusalem, Israel. Excluded were patients with brain stem lesions and/or
      bilateral signs or hemorrhagic events as diagnosed by Computerized Tomography,
      patients with Mini-Mental State Examination < 20, those who were not able to sit
      unsupported for 10 sec and those who could stand without support for more than 30
      sec. MAIN OUTCOME MEASURES: The MFRT, performed while sitting in forward and
      sideward directions. RESULTS: The MFRT in all directions on both occasions
      exhibited high reliability (intra-class correlation coefficient range, 0.90 -
      0.97). The responsiveness to the paretic side was high (effect size 0.80) and
      moderate for the forward and non-paretic side (effect size 0.57 - 0.60). A
      significant moderate correlation was found between MFRT and BM on both occasions.
      CONCLUSION: The MFRT while sitting can be reliably measured and may serve as a
      useful outcome measure in individuals with stroke 2 - 8 weeks post-event.

PMID- 18608434
TI  - A comparison of treadmill walking and overground walking in independently
      ambulant stroke patients: a pilot study.
AB  - Purpose. The purpose of the study was to compare the spatio-temporal and joint
      kinematic gait parameters of stroke patients walking on a treadmill and
      overground, to examine the assumption that patients walking on a treadmill will
      approximate the requirements of walking overground. Methods. Ten independently
      ambulant chronic stroke patients were included in the study. Vicon was used to
      collect spatio-temporal and joint kinematic data during overground walking at
      comfortable speed and at matched speed on the treadmill. Results. Walking on the
      treadmill demonstrated statistically significantly lower cadence, and longer step
      times of the non-hemiplegic and hemiplegic limbs. Absolute stance times of both
      limbs, absolute double support time, relative stance time and relative double
      support time were significantly longer during treadmill walking. Compared to
      overground walking, the inter-limb symmetries of step time, stance time, and
      stance/swing time ratio were significantly greater on the treadmill. During
      treadmill walking, joint kinematic data showed statistically significant changes
      with greater flexion of the nonhemiplegic knee and hip at initial contact, and
      less hip extension of the hemiplegic limb. Maximal ankle plantarflexion and knee
      extension of the hemiplegic limb occurred later in the gait cycle on the
      treadmill. Conclusion. These differences suggest it may be useful to use
      treadmill in conjunction with overground walking to focus on improving specific
      walking deficits in patients with stroke.

PMID- 18608435
TI  - The influence of the distance between the backrest of a chair and the position of
      the pelvis on the maximum pressure on the ischium and estimated shear force.
AB  - PURPOSE: For some people with leg disorders, the alternative to becoming
      bedridden is sitting in a wheelchair for long periods of time. The purpose of
      this study was to investigate the relation between the backrest of a chair and
      the position of the pelvis on the maximum pressure at the ischium and the
      estimated shear force encountered while sitting in a chair. METHODS: Ten healthy
      males aged 22.4 +/- 2.3 years without pathologies in the leg and/or trunk
      participated in this study. The subjects were instructed to sit in a chair and
      the pressure and shear forces were measured under three sitting conditions: In
      the standard position, a 5 cm forward position and a 10 cm forward position. The
      effects of the positions of the pelvis on the maximum pressure at the ischium
      were measured by an instrument for measuring pressure distribution and the shear
      forces were estimated using an experimental model proposed by us. RESULTS:
      Comparisons were made among the three sitting positions; the range of
      displacement of the maximum pressure point was not significant. The estimated
      shear force on the seat was 15.5 +/- 12.4 N in the standard position, 34.4 +/-
      8.5 N in the 5-cm forward position, and 53.2 +/- 16.7 N in the 10 cm forward
      position. There were significant differences among the three values (p < 0.01).
      CONCLUSIONS: Displacing the pelvis forward and leaning against the backrest tends
      to increase the shear force and raise the risk of decubitus ulcers.

PMID- 18608437
TI  - The IBM HeadTracking Pointer: improvements in vision-based pointer control.
AB  - Vision-based head trackers have been around for some years and are even beginning
      to be commercialized, but problems remain with respect to usability. Users
      without the ability to use traditional pointing devices--the intended audience of
      such systems--have no alternative if the automatic bootstrapping process fails.
      There is room for improvement in face tracking, and the pointer movement dynamics
      do not support accurate and efficient pointing. This paper describes the IBM
      HeadTracking Pointer, a system which attempts to directly address some of these
      issues. Head gestures are used to provide the end user a greater level of
      autonomous control over the system. A novel face-tracking algorithm reduces drift
      under variable lighting conditions, allowing the use of absolute, rather than
      relative, pointer positioning. Most importantly, the pointer dynamics have been
      designed to take into account the constraints of head-based pointing, with a non
      linear gain which allows stability in fine pointer movement, high speed on long
      transitions and adjustability to support users with different movement dynamics.
      User studies have identified some difficulties with training the system and some
      characteristics of the pointer motion that take time to get used to, but also
      good user feedback and very promising performance results.

PMID- 18608439
TI  - Towards an inclusive society in Asia: the invisible helping hand.
AB  - Asia has come a long way in its laborious journey towards an inclusive society -
      one that allows full participation and equality for people with disability (PWD).
      The imminent aging population in Asia has injected a new-found urgency among the
      Asian legislators to get their countries prepared in anticipation of an explosive
      number of elderly people with geriatric disabilities. From the concluded Asian
      and Pacific Decade of Disabled Persons (1993-2002) to the Biwako Millennium
      Framework (2003-2012), the efforts led by the United Nation Economic and Social
      Commission for Asia and the Pacific have been predominantly focusing on using
      government policies to build the two pillars of an inclusive society: A barrier
      free society and empowerment of the PWD. Notwithstanding that policy is the most
      powerful tool for solving the issues of the PWD, it cannot do it all by itself.
      The top-down nature of policy would better serve the cause in overcoming the
      barriers than in the empowerment of the PWD. In this paper, we advocate
      empowerment of the PWD through the use of technology. While policy provides the
      framework to integrate the PWD back into the mainstream society, technology can
      enhance their capability and give them a chance to compete in the real world. To
      popularize technology usage among the PWD, it is vital to develop an assistive
      and rehabilitative technology industry in Asia. Taking a leaf from philosopher
      Adam Smith's famed theory of the 'Invisible Hand'; the authors believe the best
      way forward for the Asian assistive and rehabilitative technology industry is to
      grow it into a sustainable and profitable one without intervention and protection
      from the government. When there is money to be made, more players will enter the
      industry, thus providing better services and innovative products at more
      competitive prices and in consequence, the PWD will become the eventual winners.

PMID- 18608442
TI  - Gait assessment during the initial fitting of an ankle foot orthosis in
      individuals with stroke.
AB  - PURPOSE: To evaluate if the measurement of gait parameters, examined during the
      fitting of an Ankle Foot Orthosis (AFO), has a beneficial effect on the gait
      pattern of individuals who were affected by a stroke. Also, this study seeks to
      provide evidence regarding the use of the portable GaitRite system in a clinical
      setting. METHOD: Before-after trial conducted at a stroke outpatient orthotic
      clinic of a freestanding rehabilitation hospital. Thirteen individuals with acute
      and 27 individuals with chronic stroke participated in the assessment of gait
      velocity, cadence, step length and stance phase. RESULTS: AFO use significantly
      improves gait velocity, cadence, step, and stride length in individuals with
      hemiparesis due to stroke. CONCLUSION: The results of the current study indicate
      that the assessment of temporo-spatial characteristics of gait can be
      incorporated into a clinical routine. This will be useful for patient education,
      justification of medical necessity of paying, monitoring progress, and in the
      decision-making process of weaning patients off orthoses.

PMID- 18608443
TI  - Design of a custom racing hand-cycle: review and analysis.
AB  - PURPOSE: This paper describes the design, manufacture and evaluation of a custom
      hand-cycle with a Delta-style frame and fork steering. The state of hand-cycle
      design and future design directions are also examined. METHOD: The design of the
      custom hand-cycle was based on these criteria: Light weight, aerodynamics,
      climbing ability, ergonomic fit and the user's specific needs. We designed and
      built a custom hand-cycle for one expert user, therefore, the user's personal
      needs were key design drivers. The hand-cycle was evaluated by the user over
      three years of use. RESULTS: During three years of evaluation and over 8000 km of
      use there were two frame failures: (i) A crack propagated around one of the tubes
      connecting the mainframe tube to the headset tube; and (ii) a crack propagated
      around the circumference of the curved part of the main frame tube directly
      behind the seat. The first failure was repaired and after the second, the device
      was retired. The evaluation of this design serves as a basis for a new set of
      design criteria. CONCLUSIONS: Large amounts of frame flexion can indicate
      eventual plastic deformation and failure. Future hand-cycle designs should see
      the use of more advanced materials, finite element analysis software, and
      continued incorporation of bicycle technology and design innovation.

PMID- 18608445
TI  - How large must a treatment effect be before it matters to practitioners? An
      estimation method and demonstration.
AB  - INTRODUCTION AND AIMS: Treatment research is sometimes criticised as lacking in
      clinical relevance, and one potential source of this friction is a disconnection
      between statistical significance and what clinicians regard to be a meaningful
      difference in outcomes. This report demonstrates a novel methodology for
      estimating what substance abuse practitioners regard to be clinically important
      differences. DESIGN AND METHODS: To illustrate the estimation method, we surveyed
      50 substance abuse treatment providers participating in the National Institute on
      Drug Abuse (NIDA) Clinical Trials Network. Practitioners identified thresholds
      for clinically meaningful differences on nine common outcome variables, indicated
      the size of effect that would justify their learning a new treatment method and
      estimated current outcomes from their services. RESULTS: Clinicians judged a
      difference between two treatments to be meaningful if outcomes were improved by
      about 10 - 12 points on the percentage of patients totally abstaining, arrested
      for driving while intoxicated, employed or having abnormal liver enzymes. A 5
      percentage-point reduction in patient mortality was regarded as clinically
      significant. On continuous outcome measures (such as percentage of days abstinent
      or drinks per drinking day), practitioners judged an outcome to be significant
      when it doubled or halved the base rate. When a new treatment meets such
      criteria, practitioners were interested in learning it. DISCUSSION AND
      CONCLUSIONS: Effects that are statistically significant in clinical trials may be
      unimpressive to practitioners. Clinicians' judgements of meaningful differences
      can inform the powering of clinical trials.

PMID- 18608447
TI  - Blood-borne virus prevalence and risk among steroid injectors: results from the
      Australian Needle and Syringe Program Survey.

PMID- 18608451
TI  - The influence of cannabis use expectancies on cannabis use and psychotic symptoms
      in psychosis.
AB  - INTRODUCTION AND AIMS: Little is known about motives or expectancies for cannabis
      use in psychotic populations, despite these cognitive factors being a central
      focus of the treatment for substance misuse in psychosis. This study examined the
      relationship between cannabis use expectancies, cannabis use and psychotic
      symptoms among cannabis using psychotic inpatients. A secondary aim was to
      determine if there were significant differences in the cannabis use expectancies
      of psychotic patients with and without Diagnostic and Statistical Manual version
      IV (DSM-IV) cannabis dependence. DESIGN AND METHODS: Participants consisted of
      101 in-patients with psychosis who had used cannabis more than five times in the
      past year. Expectancies were assessed using the Cannabis Expectancy Questionnaire
      (CEQ). The frequency of cannabis use, severity of cannabis dependence, presence
      of DSM-IV cannabis dependence and severity of psychotic symptoms were also
      assessed using standardised measures. RESULTS AND CONCLUSIONS: Results suggested
      that cannabis use expectancies were associated with cannabis use but not symptom
      variables. Expectancies for cannabis use predicted recent cannabis use and the
      presence and severity of cannabis dependence. Psychotic patients with DSM-IV
      cannabis dependence had significantly higher expectancies for negative effects
      from cannabis use. Prospective research examining the influence of motives and
      expectancies for cannabis use on cannabis use and psychotic symptoms is required
      to obtain a greater understanding of substance use in psychosis and assist with
      the development of innovative treatment interventions.

PMID- 18608453
TI  - All-cause mortality and fatal alcohol poisoning in Belarus, 1970-2005.
AB  - INTRODUCTION AND AIMS: Although alcohol appears to be an important contributor to
      the burden of disease in the countries of eastern Europe, little systematic
      research has been undertaken on its impact on mortality in the former Soviet
      republic of Belarus. There may be a number of factors underlying the particularly
      negative effect of alcohol on mortality in Belarus, including the pattern of
      drinking and use of surrogates. A solid body of research and empirical evidence
      suggests that hazardous patterns of alcohol consumption (binge drinking) lead to
      quicker and deeper intoxication, increasing the propensity for alcohol-related
      mortality. DESIGN AND METHOD: To estimate the aggregate level effect of binge
      drinking on the all-cause mortality rate, trends in the all-cause mortality and
      fatal alcohol poisoning rates (as a proxy for binge drinking) in Belarus from
      1970 to 2005 were analysed employing AutoRegressive Integrated Moving Average
      (ARIMA) time-series analysis in order to assess a bivariate relationship between
      the two time-series. RESULTS: The results of time-series analysis suggest a close
      relationship between all-cause mortality and fatal alcohol poisoning rates at the
      population level. CONCLUSIONS: This study supports the hypothesis that alcohol
      and all-cause mortality are connected closely in countries where the drinking
      culture is characterised by heavy drinking episodes and adds to the growing body
      of evidence that a substantial proportion of total mortality in Belarus is due to
      acute effects of binge drinking.

PMID- 18608459
TI  - Impaired physical health among methamphetamine users in comparison with the
      general population: the role of methamphetamine dependence and opioid use.
AB  - AIM: To examine the extent of physical health impairment among a community sample
      of methamphetamine users in comparison with the general population, and factors
      associated with impairment among this group. METHOD: A cross-sectional survey of
      309 regular methamphetamine users from Sydney. The Physical Component Scale of
      the Short Form 12 (SF-12) was used to measure impairment in physical health
      (score < 40). Age-matched general population data for the SF-12 were derived from
      the Australian National Survey of Mental Health and Well-Being. RESULTS:
      Participants had a higher prevalence of impaired physical health compared to the
      Australian general population (20% vs. 10%, p<0.05), but this effect occurred
      among only dependent methamphetamine users over 24 years of age (25 - 34 years,
      23% vs. 10%; 35 - 44 years, 41% vs. 12%). Methamphetamine dependence remained
      significantly predictive of impaired physical health after adjusting for age and
      other confounding factors. Opioid pharmacotherapy was also related strongly to
      poor physical health, accounting for 63% of participants with physical
      impairment. Other factors associated with impaired physical health were being
      female, having less than 10 years of schooling, and having been diagnosed
      previously with an anxiety disorder (p<0.05). CONCLUSION: Methamphetamine users
      are more likely to report impaired physical health than the general population,
      but this impairment is specific to older methamphetamine users who are dependent
      on the drug, particularly those who are enrolled in opioid pharmacotherapy.

PMID- 18608460
TI  - Physicochemical characterization of interaction of ibuprofen by solid-state
      milling with aluminum hydroxide.
AB  - This present study is a preliminary exploration of the affinity between a
      carboxylic model drug ibuprofen and aluminum hydroxide. Ibuprofen was comilled
      with aluminum hydroxide in different weight ratios in the solid state and was
      characterized by scanning electron microscopy (SEM), X-ray powder diffractometry
      (XRD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution
      studies. XRD and SEM studies indicated complete interaction of ibuprofen with
      aluminum hydroxide and complete amorphization of aluminum hydroxide-ibuprofen
      complexed salt as well, on comilling with aluminum hydroxide at 1:2 ratio. FTIR
      data showed the disappearance of acid carbonyl peak with the appearance and the
      corresponding increase in absorbance of new signal at 1,682 cm(-1) in the 1:1 and
      1:2 ibuprofen-aluminum hydroxide-comilled powder. The accompanied increase in the
      absorbance of carboxylate peak in the ibuprofen-aluminum hydroxide physical
      mixture, and 1:0.1, 1:0.5, 1:1, and 1:2 (IBA(pm), and IB(1)A(0.1), IB(1)A(0.5),
      IB(1)A(1), and IB(1)A(2), respectively) comilled powder indicated an acid-base
      reaction between ibuprofen and aluminum hydroxide. On storage at 40 degrees C and
      75% relative humidity (RH) for 10 weeks, XRD study showed the absence of
      reversion to the crystalline state and FTIR data revealed continued increase of
      new signal at 1,682 cm(-1) relative to carboxylic acid peak and no reappearance
      of carboxylic acid peak. In vitro dissolution studies revealed that the percent
      release of ibuprofen from the aluminum hydroxide-comilled powder is in the
      following order: IB(1)A(2) < IB(1)A(1) < ibuprofen crystal < ibuprofen milled
      alone < IB(1)A(0.1) < IB(1)A(0.5). Aluminum metal cation might have interacted to
      form a complex through the carboxyl and carbonyl groups of ibuprofen. Improved
      dissolution of drug associated with IB(1)A(0.1) and IB(1)A(0.5) is because of the
      absence of a new signal at 1,682 cm(-1) and improved amorphization of the drug to
      some extent. Dissolution of drug affected in IB(1)A(2) and IB(1)A(1) may be
      because of the insoluble stable complex formation.

PMID- 18608461
TI  - D-optimal designing and optimization of long acting microsphere-based injectable
      formulation of aripiprazole.
AB  - This work was aimed to design and optimize a long acting microsphere-based
      injectable formulation of aripiprazole by using D-optimal experimental design
      methodology. Microspheres were prepared by solvent evaporation method using PLGA
      and cholesterol as release rate retardant materials. The microspheres were
      characterized for their encapsulation efficiency, particle size, surface
      morphology, residual solvent content, and drug release behavior. Contour plots
      were plotted to study the encapsulation and release behaviour of the drug from
      the microspheres. Desirability technique was used for the optimization of
      microsphere formulation composition. By using an optimum blend of drug and
      cholesterol in the microsphere formulation it was possible to attain a consistent
      drug release for a period of 14 days. The results have confirmed that the D
      optimal experimental design technique can be successfully employed for designing
      the long acting microsphere dosage form.

PMID- 18608462
TI  - Safety, pharmacokinetics and biodistribution studies of a beta-galactoside
      prodrug of doxorubicin for improvement of tumor selective chemotherapy.
AB  - Anthracycline antibiotics, particularly doxorubicin (DOX) and daunorubicin, have
      been used extensively in the treatment of human malignancies. However,
      cardiotoxicity and multidrug resistance are significant problems that limit the
      clinical efficacy of such agents. Rational design to avoid these side effects
      includes strategies such as drug targeting and prodrug synthesis. The DOX prodrug
      N-(beta-D-glucopyranosylbenzyloxycarbonyl)-doxorubicin (prodrug 1) was
      synthesized for specific activation by beta-galactosidase, which is expected to
      release in necrotic areas of tumor lesions. Described here is the safety,
      pharmacokinetics, and biodistribution studies of a beta-galactoside prodrug of
      DOX. In vivo safety evaluation was done in the Ehrlich Ascites Carcinoma (EAC)
      tumor model. The dose of DOX was 8 mg/kg and the dose of prodrug was 8 mg/kg and
      24 mg/kg of DOX equivalents. Our results on cytotoxicity, which demonstrated
      compression in the number of EAC cells and their viability, substantiate these
      data. Prodrug 1 was safe up to a dose of 24 mg/kg of DOX equivalents in EAC mice.
      The pharmacokinetics and biodistribution of prodrug (300 mg/kg) in normal mice
      were determined and compared with DOX (20 mg/kg). Administration of DOX in normal
      mice resulted in a peak plasma concentration of 19.45 microM (t = 30 minutes).
      Prodrug injection resulted in 3- to 16-fold lower concentrations in the tissues
      of normal mice. As it is more polar, lower levels were observed in tissues and
      plasma in contrast to the parent compound DOX. In vivo safety studies have shown
      that prodrug 1 had a maximum tolerated dose compared with DOX and led to improved
      pharmacokinetics in normal mice.

PMID- 18608463
TI  - Investigation into the mechanism by which cyclodextrins influence transdermal
      drug delivery.
AB  - The objective of this study was to investigate the mechanism by which
      hydroxypropyl-beta-cyclodextrin (HPCD) increases transdermal permeation. Hairless
      mouse skin was pretreated with HPCD solutions for up to 4 h. After removing the
      HPCD, corticosteroid-containing suspensions were applied and the transdermal flux
      and skin accumulation of two model drugs were investigated. After pretreatment,
      changes to the stratum corneum endothermic melting transitions were determined as
      an indication of HPCD-induced lipid disorganization. Results demonstrated that
      HPCD pretreatment had no significant effect on the transdermal permeation or skin
      accumulation of the model corticosteroids. These findings suggest that HPCD
      functions to enhance the apparent solubility of the drug in the formulation, thus
      increasing transdermal permeation rather than extracting lipids from the skin.

PMID- 18608465
TI  - Simple and sensitive HPLC method with fluorescence detection for the measurement
      of ibuprofen in rat plasma: application to a long-lasting dosage form.
AB  - A simple and sensitive high-performance liquid chromatography (HPLC) assay
      applied to the measurement of ibuprofen in rat plasma has been developed. Two
      parameters have been investigated to improve ibuprofen detectability using
      fluorescence detection: variation of mobile phase pH and the use of beta
      cyclodextrin (beta-CD). Increasing the pH value from 2.5 to 6.5 and adding 5 mM
      beta-CD enhanced the fluorescence signal (lambda(exc) = 224 nm; lambda(em) = 290
      nm) by 2.5 and 1.3-fold, respectively, when using standards. In the case of
      plasma samples, only pH variation significantly lowered detection and
      quantification limits, down to 10 and 35 ng/mL, respectively. Full selectivity
      was obtained with a single step for plasma treatment, that is, protein
      precipitation with acidified acetonitrile. The validated method was applied to a
      pharmacokinetic study of ibuprofen encapsulated in microspheres and
      subcutaneously administered to rats.

PMID- 18608464
TI  - Synthesis of piperazinylalkyl ester prodrugs of ketorolac and their in vitro
      evaluation for transdermal delivery.
AB  - Ketorolac, an NSAID, has low intrinsic permeation capacity through the skin. In
      this work, seven piperazinylalkyl ester prodrugs of ketorolac were synthesized to
      enhance its skin permeation. The chemical hydrolysis and the stability in human
      serum at 37 degrees C were investigated in buffer solutions (pH 5.0 and 7.4) and
      in 80% human serum (pH 7.4), respectively. The prodrugs were chemically more
      stable at pH 5.0 than at pH 7.4 with prodrug 8 being the most stable (t(1/2) =
      119.75 h and 11.97 h at pH 5 and 7.4, respectively). The prodrugs' t(1/2) in
      human serum ranged from 0.79 to 3.92 min. The prodrugs' aqueous solubility was
      measured in buffer solution at pH 5.0 and 7.4 and Log P(app) was measured by
      partitioning between buffer solution (pH 5.0 and 7.4) and n-octanol. The prodrugs
      were more lipophilic than ketorolac at pH 7.4. Skin permeation of ketorolac and
      prodrug 8, the most stable chemically, through rat skin was studied at pH 5.0 and
      7.4. Prodrug 8 enhanced permeation by 1.56- and 11.39-fold at pH 5 and 7.4,
      respectively. This is attributed to higher lipophilicity at pH 7.4 and higher
      aqueous solubility at pH 5 compared to ketorolac.

PMID- 18608466
TI  - Wet process-induced phase-transited drug delivery system: a means for achieving
      osmotic, controlled, and level A IVIVC for poorly water-soluble drug.
AB  - A phase-transited, nondisintegrating, controlled release, asymmetric membrane
      capsular system for poorly water-soluble model drug flurbiprofen was developed
      and evaluated both in vitro and in vivo for osmotic and controlled release of the
      drug. Asymmetric membrane capsules (AMCs) were prepared using fabricated glass
      mold pins through wet phase inversion process. Effect of varying osmotic pressure
      of the dissolution medium on drug release was studied. Membrane characterization
      by scanning electron microscopy showed an outer dense region with less pores and
      an inner porous region for the prepared asymmetric membrane. In vitro release
      studies for all the prepared formulations were carried out (n = 6). Statistical
      test was applied for in vitro drug release at p > .05. Predicted in vivo
      concentration from in vitro release data closely matched the minimum effective
      concentration (in vivo) level achieved by the drug from its release through phase
      transited AMC in rabbits for the first hour. The drug release was found to be
      independent of the pH but dependent on the osmotic pressure of the dissolution
      medium. In vivo pharmacokinetic studies showed level A correlation (R(2) > .99)
      with 42.84% relative bioavailability compared to immediate release tablet of
      flurbiprofen. Excellent correlation achieved suggested that the in vivo
      performance of the AMCs could be accurately predicted from their in vitro release
      profile.

PMID- 18608467
TI  - Preparation and bioavailability of sustained-release doxofylline pellets in
      beagle dogs.
AB  - The objective of this study was to develop doxofylline-loaded sustained-release
      pellets coated with Eudragit NE30D alone (F1) or blend of Eudragit RL30D/RS30D
      (F2) and further evaluate their in vitro release and in vivo absorption in beagle
      dogs. Doxofylline-loaded cores with a drug loading of 70% (w/w) were prepared by
      layering drug-MCC powder onto seed cores in a centrifugal granulator and then
      coating them with different kinds of polymethacrylates in a bottom-spray
      fluidized bed coater. Dissolution behaviour of these formulations was studied in
      vitro under various pH conditions (from pH 1.2 to pH 7.4) to evaluate the effect
      of pH on drug release profiles. It was found that F2 produced a better release
      profile than F1 did and two different release mechanisms were assumed for F1 and
      F2, respectively. The relative bioavailability of the sustained-release pellets
      was studied in six beagle dogs after oral administration in a fast state using a
      commercially available immediate release tablet as a reference. Coated with
      Eudragit NE30D and a blend of Eudragit RL30D/RS30D (1:12), at 5% and 8% coating
      level, respectively, the pellets acquired perfect sustained-release properties
      and good relative bioavailability, with small fluctuation of drug concentration
      in plasma. But combined use of mixed Eudragit RL30D/RS30D polymers with proper
      features as coating materials produced a longer T(max), a lower C(max) and a
      little higher bioavailability compared to F1 (coated with Eudragit NE30D alone).
      The C(max), T(max) and relative bioavailability of F1 and F2 coated pellets were
      15.16 microg/ml, 4.17 h, 97.69% and 11.41 microg/ml, 5 h, 101.59%, respectively.
      Also a good linear correlation between in vivo absorption and in vitro release
      was established for F1 and F2, so from the dissolution test, formulations in vivo
      absorption can be properly predicted.

PMID- 18608469
TI  - Bioavailability of clarithromycin cyclodextrin ternary complexes upon oral
      administration to healthy beagle dogs.
AB  - The dissolution profiles of clarithromycin (CLM) and its beta-cyclodextrin-citric
      acid ternary complexes (CTC) were examined. CTC showed an enhanced dissolution
      rate in pH 6.8 phosphate buffers. The relative bioavailability was evaluated by
      comparing area under the plasma concentration-time curve (AUC) of the pure CLM
      with that of its cyclodextrin-citric acid ternary complexes those were filled
      into hard gelatin capsules. To compare the pharmacokinetic behavior, both plasma
      levels of parent compound and the active metabolite 14-OH-CLM concentrations were
      estimated. The relative bioavailability value as the ratios of CLM of mean total
      AUC for CTC relative to CLM was 120.3%. The relative bioavailability value as the
      ratios of 14-OH CLM of mean total AUC for CTC relative to CLM was 95.3%. The
      results suggest that the absorption of CTC in beagle dogs was slightly improved
      because of the enhanced dissolution rate of CTC at pH 6.8.

PMID- 18608468
TI  - Enhanced in vivo absorption of itraconazole via stabilization of supersaturation
      following acidic-to-neutral pH transition.
AB  - Previous attempts to improve the dissolution and absorption properties of
      itraconazole (ITZ) through advanced formulation design have focused only on
      release in acidic media; however, recent reports indicate that absorption occurs
      primarily in the proximal small intestine. This suggests that enhancing
      supersaturation of ITZ in neutral aqueous environments is essential for improving
      absorption. The aim of this study was to evaluate different polymeric stabilizers
      with either immediate release (IR) (Methocel E5, Methocel E50, Kollidon 12, and
      Kollidon 90) or enteric release (EUDRAGIT L 100-55, HP-55, and HP-55S) properties
      to determine the chemical and physical attributes of the polymeric stabilizers
      that promote supersaturation of ITZ in neutral media. Each amorphous composition
      was produced by hot-melt extrusion and characterized by differential scanning
      calorimetry. Dissolution testing by a supersaturated acidic-to-neutral pH change
      method was conducted on each composition. Testing of IR compositions revealed
      that Methocel was a superior stabilizer compared with Kollidon owing to stronger
      intermolecular interaction with ITZ molecules in solution. Increasing the
      molecular weight of polymers was found to promote ITZ supersaturation and was
      most likely attributable to increased solution viscosity resulting in retention
      of ITZ molecules in an enthalpically favored association with the polymer for
      extended durations. Of the enteric polymeric stabilizers, EUDRAGIT L 100-55 was
      found to be superior to both HP-55 grades because of its greater permeability to
      acid that allowed for improved hydration of ITZ in the acid phase as well as a
      greater number of free hydroxyl groups on the polymer backbone that presumably
      helped to stabilize ITZ in solution. The Methoceltrade mark E50 and EUDRAGIT L
      100-55 formulations were evaluated for in vivo drug absorption in male Sprague
      Dawley rats and were found to produce a threefold greater ITZ absorption over our
      previously reported IR formulations. The results of this study confirmed the
      hypothesis that supersaturation of ITZ following an acidic-to-neutral pH
      transition in vitro correlates directly to in vivo absorption.

PMID- 18608470
TI  - Protection by Chinese herbs against Doxorubicin-induced focal and segmental
      glomerulosclerosis in rats.
AB  - The objective of this study was to evaluate the efficacy of Chinese herbs on
      Doxorubicin-induced focal and segmental glomerulosclerosis (FSGS) in rats. Twenty
      age-matched male Wistar rats were divided into two groups: group A (n = 10) given
      only water ad libitum served as the control group and group B (n = 10) was given
      Chinese herbs (40 ml/kg with drug concentration 1.75 g/ml) beginning at day zero.
      All rats were administered doxorubicin (7 mg/kg) intravenously. All the rats were
      placed in metabolic cages at day 0, 7, 14, 21, and 28, and daily proteinuria was
      measured. At day 28, the animals were killed by cervical dislocation, followed by
      immediate organ collection for histologic analysis of kidneys; blood was
      collected by tail vein and cardiac puncture (at day 28) for the measurement of
      serum albumin. Body weight (BW) and food intake were recorded. The rats in groups
      A and B demonstrated severe susceptibility to doxorubicin injection with the
      onset of proteinuria (80-100 mg/24h) at day 7. The rats in group B were partly
      resistant to doxorubicin nephropathy with decreasing proteinuria and increasing
      serum albumin compared with group A (p < 0.05). All 10 rats in group A developed
      at least 5% glomerulosclerosis with tubular casts at day 28. In contrast, the
      rats in group B developed less severe histologic renal disease. The difference in
      histologic scores between the two groups were significant at day 28 (12 in group
      B vs. 20 in group A, p = 0.002). Food intake of Group B animals progressively
      increased to reach 67-73% of those observed before the doxorubicin administration
      with 28-43% in Group A. After the 4-wk experimental period, BW in Group A
      decreased more significantly than that in Group B (-20 +/- 3 and -16 +/- 1%,
      respectively, p = 0.035, paired T test). Chinese herbs seem to reduce proteinuria
      and attenuate renal histologic severity in rats with doxorubicin-induced FSGS and
      may offer an alternative to the treatment of FSGS.

PMID- 18608471
TI  - The work compatibility improvement framework: an assessment of the worker-work
      environment interaction in the manufacturing sector.
AB  - The manufacturing sector in the US is challenged by high health care costs and
      shortage of qualified workers, which are largely attributed to the degree of fit
      between the worker and work environment. In this regard, a healthy worker-work
      environment interface is a necessary and sufficient condition for the containment
      of health care costs and the retaining/attraction of highly qualified knowledge
      workers and should be based on the principles of optimum physical, cognitive and
      emotional health for the workers. In prior research, the Work Compatibility
      Improvement Framework (WCIF) was introduced as a vehicle to address these issues
      and was defined as the identification, improvement and maintenance of the well
      being characteristics of the workforce and its interaction with the work
      environment through the application of engineering, medicine, management and
      human sciences methodologies, technologies and best practices. This paper
      advances WCIF by examining its applications in manufacturing with regard to the
      evaluation of working conditions impacting musculoskeletal/stress outcome
      measures. A study was conducted in a machining department of a bag packaging
      manufacturer in the Midwest of the United States. The work tasks were planned and
      executed with regard to the following aims: (1) to compute work compatibility as
      a function of work demands and energisers; (2) to establish whether the
      prevalence of musculoskeletal/stress disorders increases with a decrease in the
      quality of worker-work environment interface in terms of work compatibility level
      and other work factors such as shift and job category. A major finding is that a
      'poor' work environment (a function of all work domains) results in
      musculoskeletal/stress disorders that are 105% and 67% higher than those for a
      'good' work environment. The evening shift exhibited the poorest compatibility
      followed by the night shift relative to the day shift. Application of the work
      compatibility approach demonstrated the detection of non-added value work. It is
      essential to evaluate the various domains of worker-work environment interface to
      uncover the root causes that tend to sub-optimise the
      physical/cognitive/emotional health of the workforce. The WCIF was used to
      uncover the non-value added effort in the work process. These findings will have
      major implications for developing and implementing customised design
      interventions with the aim to maximise the benefit and reduce the cost of
      employees in a manufacturing enterprise. The study findings suggest that the WCIF
      should be pursued as a potential strategic tool for optimising human performance
      in an enterprise to create healthy workplaces.

PMID- 18608472
TI  - Effects of tactile cueing on concurrent performance of military and robotics
      tasks in a simulated multitasking environment.
AB  - This study examined the concurrent performance of military gunnery, robotics
      control and communication tasks in a simulated environment. More specifically,
      the study investigated how aided target recognition (AiTR) capabilities
      (delivered either through tactile or tactile + visual cueing) for the gunnery
      task might benefit overall performance. Results showed that AiTR benefited not
      only the gunnery task, but also the concurrent robotics and communication tasks.
      The participants' spatial ability was found to be a good indicator of their
      gunnery and robotics task performance. However, when AiTR was available to assist
      their gunnery task, those participants of lower spatial ability were able to
      perform their robotics tasks as well as those of higher spatial ability. Finally,
      participants' workload assessment was significantly higher when they teleoperated
      (i.e. remotely operated) a robot and when their gunnery task was unassisted.
      These results will further understanding of multitasking performance in military
      tasking environments. These results will also facilitate the implementation of
      robots in military settings and will provide useful data to military system
      designs.

PMID- 18608473
TI  - Modelling foot height and foot shape-related dimensions.
AB  - The application of foot anthropometry to design good-fitting footwear has been
      difficult due to the lack of generalised models. This study seeks to model foot
      dimensions so that the characteristic shapes of feet, especially in the midfoot
      region, can be understood. Fifty Hong Kong Chinese adults (26 males and 24
      females) participated in this study. Their foot lengths, foot widths, ball girths
      and foot heights were measured and then evaluated using mathematical models. The
      results showed that there were no significant allometry (p > 0.05) effects of
      foot length on ball girth and foot width. Foot height showed no direct
      relationship with foot length. However, a normalisation with respect to foot
      length and foot height resulted in a significant relationship for both males and
      females with R(2) greater than 0.97. Due to the lack of a direct relationship
      between foot height and foot length, the current practice of grading shoes with a
      constant increase in height or proportionate scaling in response to foot length
      is less than ideal. The results when validated with other populations can be a
      significant way forward in the design of footwear that has an improved fit in the
      height dimension.

PMID- 18608474
TI  - Investigation of task performance variations according to task requirements and
      alertness across the 24-h day in shift workers.
AB  - The study investigated time-of-day effects on task performance in shift workers
      in different tasks (reaction time, discrimination, probe recognition, free
      recall), by varying task-specific features. On each of six recordings, each
      programmed on a different day and in a randomised order, operators rated
      alertness and performed different tasks. Self-rated alertness varied according to
      a typical diurnal trend. Time of day also affected reaction time (slower
      responses at 03:00 hours), discrimination performance (lower accuracy at 03:00
      hours in the most difficult condition) and recall (superior recall at 07:00 and
      11:00 hours following deeper processing at encoding). The data demonstrated time
      of-day effects on cognitive processes also involved in many real-job activities,
      despite the lack of control for a number of exogenous factors known to interfere
      with performance in work settings. Since in the cognitively more loaded tasks,
      time-of-day effects depended on task conditions, the findings are of operational
      concern in shift-work situations involving differential task requirements. In a
      real-job setting, performance variations were observed according to time of day
      and task requirements in a set of cognitively more or less demanding tasks. Task
      specific research across the 24-h day enables a better understanding of
      operators' tasks and the development of supporting technology.

PMID- 18608475
TI  - Adaptive coordination in cardiac anaesthesia: a study of situational changes in
      coordination patterns using a new observation system.
AB  - Patient care in hospital settings requires coordinated team performance. Studies
      in other industries show that successful teams adapt their coordination processes
      to the situational task requirements. This prospective field study aimed to test
      a new observation system and investigate patterns of adaptive coordination within
      operating room teams. A trained observer recorded coordination activities during
      24 cardiac surgery procedures. The study tested whether different patterns occur
      during different phases of and between different types of surgical procedures
      (two-way multivariate ANOVA with repeated measure). A statistically significant
      increase was found in clinical and coordination activities in phases of the
      operation with high task interdependence. The highest level of 'coordination via
      the work environment' (i.e. an implicit coordination mechanism) was recorded
      during the actual procedure on the beating heart. These findings prove the
      sensitivity of the observation system developed and evaluated in this study and
      provide insight into patterns of adaptive coordination in cardiac anaesthesia.
      This study furthers our understanding of adaptive coordination as a cornerstone
      of effective team performance in complex work environments. Using a new
      observation system, it describes patterns employed by health care professionals
      in response to changing task demands in an acute patient care setting.

PMID- 18608476
TI  - Lower extremity preventive measures for slips - joint moments and myoelectric
      analysis.
AB  - This study investigated the lower extremity preventive measures for slips on
      simulated slippery surfaces in construction worksites. A total of 15 harnessed
      Chinese males walked without slips on a 5-m walkway in 16 simulated conditions 10
      times at their natural cadence. Joint moments were calculated from kinetics,
      kinematics and anthropometric data recorded from a force plate, a Novel Pedar
      system and a motion analysis system. Data were evaluated from footstrike to mid
      stance at 10%-stance intervals. Electromyography signals from tibialis anterior,
      gastrocnemius, rectus femoris and biceps femoris in one stride were evaluated in
      four phases, including early/late stance and swing. Results showed that lower
      extremity preventive measures for slips included prolonged ankle plantar flexion
      moments from 25% to 92% stance, increased ankle plantar flexion moments from 30%
      stance to mid-stance, and diminished knee extension moments from 10% to 30%
      stance. Higher activity of rectus femoris and gastrocnemius were found in the
      late stance and the swing phase respectively.

PMID- 18608477
TI  - Fatigue influences the dynamic stability of the torso.
AB  - Fatigue in the extensor muscles of the torso affects neuromuscular recruitment
      and control of the spine. The goal of this study was to test whether fatigue
      influences stability of dynamic torso movements. A controlled laboratory
      experiment measured the change in the maximum finite-time Lyapunov exponent,
      lambda(max), before and after fatigue of the extensor muscles. Non-linear
      analyses were used to compute stability from the embedding dimension and Lyapunov
      exponent recorded during repetitive dynamic trunk flexion tasks. Torso extensor
      muscles were fatigued to 60% of their unfatigued isometric maximum voluntary
      exertion force then stability was re-measured. Independent variables included
      fatigue, task asymmetry and lower-limb constraint. lambda(max) values increased
      with fatigue suggesting poorer dynamic stability when fatigued. Embedding
      dimension declined with fatigue indicating reduced dynamic complexity when
      fatigued. Fatigue-related changes in spinal stability may contribute to the risk
      of low-back injury during fatiguing occupational lifting tasks. The findings
      reported here indicate that one mechanism by which fatigue contributes to low
      back disorders may be spinal instability. This information may contribute to the
      development of ergonomic countermeasures to help prevent low back disorders.

PMID- 18608478
TI  - What happens next? Predicting other road users' behaviour as a function of
      driving experience and processing time.
AB  - Hazard perception is one of the most important facets of driving and if the
      appropriate diagnostic tool is used it can discriminate between novice and
      experienced drivers. In this study video clips of actual driving scenarios were
      shown to novice and experienced drivers. The clips were stopped just prior to
      hazard onset and either the screen went black or the final still image stayed on
      the screen. Participants were then asked five questions about what happened next.
      This variant of the hazard perception test allowed the influence of processing
      time to be included and the level of situation awareness to be measured.
      Experienced drivers significantly anticipated more correct hazardous outcomes
      than novice drivers when the screen went black. Novice drivers benefited from the
      extra processing time afforded by the image remaining on the screen and
      significantly anticipated more hazards when the image remained on the screen than
      when it went black. The findings indicate that when processing time is
      manipulated, hazard perception accuracy reveals experiential differences. These
      differences are discussed with reference to hazard perception and situation
      awareness. This research informs the current controversy over whether hazard
      perception is a good diagnostic tool for driving performance. It identifies
      potential confounds in previous work and demonstrates that experiential
      differences can be found if the appropriate tests are used. Further, it suggests
      improvements for new hazard perception tests.

PMID- 18608479
TI  - Stepping over obstacles of different heights and varied shoe traction alter the
      kinetic strategies of the leading limb.
AB  - This study aims to investigate the effects of shoe traction and obstacle height
      on friction during walking to better understand the mechanisms required to avoid
      slippage following obstacle clearance. Ten male subjects walked at a self
      selected pace during eight different conditions: four obstacle heights (0%, 10%,
      20% and 40% of limb length) while wearing two different pairs of shoes (low and
      high traction). Frictional forces were calculated from the ground reaction forces
      following obstacle clearance, which were sampled with a Kistler platform at 960
      Hz. All frictional peaks increased with increases in obstacle height. Low
      traction shoes yielded smaller peaks than high traction shoes. The transition
      from braking to propulsion occurred sooner due to altered control strategies with
      increased obstacle height. Collectively, these results provided insights into
      kinetic strategies of leading limb when confronted with low traction and high
      obstacle environments. This study provides valuable information into the
      adaptations used to reduce the potential of slips/falls when confronted with
      environments characterised by low shoe-floor friction and obstacles. It also
      provides the necessary foundation to explore the combined effects of shoe
      traction and obstacle clearance in elderly people, more sensitive to slippage.

PMID- 18608480
TI  - Kinematics and kinetics of gait on stilts: identification of risk factors
      associated with construction stilt use.
AB  - This study investigated kinematics and kinetic strategies and identified risk
      factors associated with gait on stilts. A six-camera motion-analysis system and
      two force platforms were used to test 20 construction workers for straight
      walking or turning, with or without carrying tools while wearing safety shoes or
      stilts at different heights. The results indicated that gait on stilts is
      characterised by increases in stride length, step width and the percentage of
      double support period, decreases in cadence, minimum foot clearance and a weaker
      heel-strike and push-off. Stilts place greater joint loadings on lower
      extremities to compensate for the added weight and limitation in joint mobility.
      Smaller foot clearances found for gait on stilts constitute an increased risk for
      tripping over obstacles. Workers may need to avoid prolonged use of stilts to
      alleviate stresses on the joints. This study was conducted to determine to what
      extent stilts alter the gait strategies and to explain the compensatory
      movements. Prior to this study, there has been little substantive research to
      evaluate the stresses and potential injuries associated with stilts.

PMID- 18608481
TI  - Energy expenditure of cycle rickshaw pullers in different places in India.
AB  - The cycle rickshaw is a popular transportation device. The aim of the study was
      to assess workload of cycle rickshaw pullers--physiological and subjective at
      four different places in India. Subjects were instructed to pull a cycle rickshaw
      with two passengers, for 20 min. Working and recovery heart rates were recorded.
      The mean values of energy expenditure of pulling a cycle rickshaw varied from
      23.5 +/- 2.66 to 25.35 +/- 1.51 kJ/min. Relative cardiac strain and cardiac cost
      indicated that the job is 'heavy' to 'very heavy'. Subjective assessment of
      workload was 'heavy' to 'very heavy'. The combined workload assessed from
      physiological parameters and subjective assessment indicated that the job could
      be categorised as 'heavy' to 'very heavy' at all the places studied and needs to
      be reduced by redesigning the structural and functional components of the cycle
      rickshaw. The rickshaw pullers carry out the jobs many times per day, sometimes
      without proper rest pauses between trips. The outcome of the research project is
      beneficial for cycle rickshaw pullers, health administrators as well as
      manufacturers of cycle rickshaws. Primarily, the manufacturers would be able to
      use the data for producing a newer model of cycle rickshaw, which would require
      less energy to drive. The health administrators would be able to take policy
      decisions for administering better health care for the unorganised and
      underprivileged workers. The pullers could be guided into taking care of their
      health by improving their work practice, i.e. taking a sufficient rest pause
      between trips.

PMID- 18608482
TI  - A systematic exploration of distal arm muscle activity and perceived exertion
      while applying external forces and moments.
AB  - The purpose of this study was to systematically explore and describe the response
      of selected hand and forearm muscles during a wide range of static force and
      moment exertions. Twenty individuals with manual work experience performed
      exertions in power grip, pulp pinch and lateral pinch grips. Electromyography
      (EMG) from eight sites of the hand and forearm, grip force as well as ratings of
      perceived exertion (RPE) were monitored as each participant exerted approximately
      350 short (5 s) static grip forces and external forces and moments. As expected,
      strong relationships were found between grip force alone without other actions
      and muscle activation. When the hand was used to grip and transmit forces and
      moments to the environment, the relationships between grip force and muscle
      activation were much weaker. Using grip force as a surrogate for forearm and hand
      tissue loading may therefore be misleading.

PMID- 18608483
TI  - Validation of a short-term memory test for the recognition of people and faces.
AB  - Memorising and processing faces is a short-term memory dependent task of utmost
      importance in the security domain, in which constant and high performance is a
      must. Especially in access or passport control-related tasks, the timely
      identification of performance decrements is essential, margins of error are
      narrow and inadequate performance may have grave consequences. However,
      conventional short-term memory tests frequently use abstract settings with little
      relevance to working situations. They may thus be unable to capture task-specific
      decrements. The aim of the study was to devise and validate a new test, better
      reflecting job specifics and employing appropriate stimuli. After 1.5 s (short)
      or 4.5 s (long) presentation, a set of seven portraits of faces had to be
      memorised for comparison with two control stimuli. Stimulus appearance followed 2
      s (first item) and 8 s (second item) after set presentation. Twenty eight
      subjects (12 male, 16 female) were tested at seven different times of day, 3 h
      apart. Recognition rates were above 60% even for the least favourable condition.
      Recognition was significantly better in the 'long' condition (+10%) and for the
      first item (+18%). Recognition time showed significant differences (10%) between
      items. Minor effects of learning were found for response latencies only. Based on
      occupationally relevant metrics, the test displayed internal and external
      validity, consistency and suitability for further use in test/retest scenarios.
      In public security, especially where access to restricted areas is monitored,
      margins of error are narrow and operator performance must remain high and level.
      Appropriate schedules for personnel, based on valid test results, are required.
      However, task-specific data and performance tests, permitting the description of
      task specific decrements, are not available. Commonly used tests may be
      unsuitable due to undue abstraction and insufficient reference to real-world
      conditions. Thus, tests are required that account for task-specific conditions
      and neurophysiological characteristics.

PMID- 18608484
TI  - Occurrence of benzene as a heat-induced contaminant of carrot juice for babies in
      a general survey of beverages.
AB  - A survey of benzene contamination of 451 beverage samples, using headspace
      sampling combined with gas chromatography and mass spectrometry (HS-GC/MS) with a
      quantification limit of 0.13 microg l(-1), was conducted. Artefactual benzene
      formation during headspace sampling was excluded by gentle heating at 50 degrees
      C only and adjustment of sample pH to 10. The incidence of benzene contamination
      in soft drinks, beverages for babies, alcopops and beer-mixed drinks was
      relatively low, with average concentrations below the EU drinking-water limit of
      1 microg l(-1). Significantly higher concentrations were only found in carrot
      juice, with the highest levels in carrot juice specifically intended for infants.
      About 94% of 33 carrot juice for infants had detectable benzene levels, with an
      average concentration of 1.86 +/- 1.05 microg l(-1). Benzene contamination of
      beverages was significantly correlated to iron and copper concentrations, which
      act as catalyst in benzene formation. The formation of benzene in carrot juice
      was predominantly caused by a heat-induced mechanism, which explains the higher
      levels in infant carrot juices that are subject to higher heat-treatment to
      exclude microbiological contamination.

PMID- 18608485
TI  - Decreasing concentrations of PCDD/Fs in pork based on Korean monitoring in years 
      2002 and 2005.
AB  - The congener-specific profiles of PCDD/Fs in domestic and imported pork monitored
      in South Korea in years 2002 and 2005 were compared. Total concentrations of
      PCDD/Fs decreased from 2002 to 2005, but displayed a similar pattern of
      congeners. In neither 2002 nor 2005 were either 2,3,7,8-TCDD or 2,3,7,8-TCDF
      detected. The mean concentrations of PCDD/Fs in domestic and imported pork were
      8.29 pg g(-1) fat from 106 samples in 2002 and 4.03 pg g(-1) fat from 90 samples
      in 2005. However, the contribution of PCDDs increased about four times with
      respect to toxic equivalent (TEQ) level and about 1.5 times in terms of
      concentration in the monitoring results from 2005 compared with 2002, and the
      PCDF contribution decreased substantially. This suggests that the main source of
      dioxins in pork probably changed to a larger portion coming from animal feeds
      than environmental sources of exposure. The estimated human intakes of PCDD/Fs
      originating from pork in the South Korean diet were calculated as 0.029 and 0.019
      pg TEQkg(-1) body weight day(-1) for the upper bound exposure in 2002 and 2005,
      respectively. The values represent low intakes when compared with the both Korean
      tolerable daily intake (TDI) (4 pg TEQkg(-1) body weight day(-1)) and World
      Health Organization TDI (1-4 pg TEQkg(-1) body weight day(-1)).

PMID- 18608487
TI  - Variation in heavy metals and microelements in South African medicinal plants
      obtained from street markets.
AB  - South African medicinal plants are traditionally harvested from a wide range of
      undisclosed locations by plant gatherers. Thus, there is a risk that plant
      material may be exposed to a variety of pollutants. The variation in five heavy
      metals (arsenic, cadmium, cobalt, nickel, and lead) and six essential elements
      (boron, copper, iron, manganese, molybdenum, and zinc) was determined in commonly
      used South African medicinal plants obtained from street markets. Elemental
      content was determined using inductively coupled plasma optical emission
      spectrophotometry. The reliability of the procedure was ensured by analysing a
      certified reference material. Medicinal plant samples contained arsenic and
      cadmium at levels exceeding the World Health Organization limits of 1 and 0.3 mg
      kg(-1) respectively. Lead and nickel were detected in all samples. Elevated iron
      and manganese levels were recorded in certain plant species. Multiple metal
      contamination of parts of medicinal plants gives grounds for concern. This study
      emphasizes the unsafe consequences of the South African practice of collecting
      medicinal plants from undisclosed locations and making these readily available to
      the public.

PMID- 18608488
TI  - Solid-phase microextraction/gas-chromatographic/mass spectrometric analysis of p
      dichlorobenzene and naphthalene in honey.
AB  - Protection of honeycombs from the Wax moth, Galleria mellonella, involves the use
      of physical, biological or chemical control methods. As chemical control may
      result in residues in the extracted honey, the presence of p-dichlorobenzene and
      naphthalene residues was investigated by solid-phase microextraction (SPME)
      coupled to gas-chromatographic/mass spectrometry (GC/MS). The method was linear
      between 5 and 200 microg kg(-1) honey for p-dichlorobenzene and 1 and 200 microg
      kg(-1) for naphthalene. Limits of detection were 1 and 0.1 microg kg(-1),
      respectively, for p-dichlorobenzene and naphthalene, while relative standard
      deviations were 2.6 and 7.9%, respectively. Application of the method to 90
      unifloral Greek honeys revealed that, in 25.6% of the samples, the concentration
      of either one of the pesticides exceeded the maximum residue level (MRL). Maximum
      concentrations were 163.03 microg kg(-1) honey for p-dichlorobenzene and 193.74
      microg kg(-1) honey for naphthalene. Naphthalene was found in traceable amounts
      in 78.9% of the samples, but only 5.6% of them contained concentrations above the
      MRL, which indicates the use of pre-contaminated honeycomb foundations or built
      combs. Nevertheless, because naphthalene is naturally present in some plant
      species growing in Greece, the contribution of nectar from such a floral source
      should not be overlooked.

PMID- 18608489
TI  - Risk assessment of aflatoxins in food in Africa.
AB  - Aflatoxins are secondary metabolites of the fungi Aspergillus flavus and A.
      parasiticus, occur widely on many staple foods and cause a broad range of
      detrimental health effects in animals and humans. As a consequence, maximum
      tolerated levels (MTLs) have been legislated in many countries. However, in
      developing countries where food safety compliance can be low and significant
      levels of the food supply are locally consumed by the producers or purchased at
      local markets, more comprehensive strategies are required. In this regard, risk
      analysis with its components of risk assessment, risk management and risk
      communication, is an important tool in dealing with food safety issues. Risk
      assessment for aflatoxin B(1) in Africa has been performed using the carcinogenic
      potency, established by the Joint FAO/WHO Expert Committee on Food Additives
      (JECFA) and applying it to typical food products and consumption across the
      continent, to illustrate the significant health implications caused by the intake
      of high levels of contaminated foods. Highlighted in this assessment is the fact
      that even low levels of contamination, which might of themselves fall within
      legislated limits, can have serious health implications due to high levels of
      consumption, i.e. meeting a MTL does not of itself guarantee food safety. Recent
      developments have highlighted the growth retardation and immune suppression
      caused by aflatoxin exposure in human populations in west Africa. Using the
      limited data available on both these health effects, a first step has been taken
      to incorporate them into a risk assessment paradigm quantifying the risk of
      immunosuppression, malnutrition and stunting in children exposed to aflatoxins
      and highlighting again how excessive consumption of foods meeting MTLs can carry
      significant health risks.

PMID- 18608491
TI  - Nitrite and nitrate content in meat products and estimated intake in Denmark from
      1998 to 2006.
AB  - The content of nitrite and nitrate in cured meat products has been monitored in
      Denmark seven times between 1995 and 2006. The maximum permitted added amounts of
      sodium nitrite in Denmark (60 mg kg(-1) for most products up to 150 mg kg(-1) for
      special products) have not been exceeded, except for a few samples back in 2002.
      The intake, mean and intake distribution of sodium nitrite have been calculated
      from 1998 to 2006 with data from the Danish dietary survey conducted in 2000-02
      on Danes from four to 75 years of age. The amounts used by industry have been
      relatively stable through the whole period with levels varying between 6 and 20
      mg sodium nitrite kg(-1) with sausages, meat for open sandwiches and salami-type
      sausages being the greatest contributors. The mean intake of sodium nitrate was
      around 1 mg day(-1), which is very low compared with the total intake of 61 mg
      day(-1). The mean intake of sodium nitrite was 0.017 and 0.014, 0.009 and 0.008,
      and 0.007 and 0.003 mg kg(-1) body weight day(-1) for men and women in the age
      groups 4-5, 6-14 and 15-75 years, respectively, which was much lower than the
      acceptable daily intake (ADI) of 0.09 mg kg(-1) body weight day(-1). The 99th
      percentile for the group of 4-year-olds was 0.107 and 0.123 mg kg(-1) body weight
      day(-1) for boys and girls, respectively, and the 95th percentile was 0.057 and
      0.073 mg kg(-1) body weight day(-1) for boys and girls, respectively, highest for
      the girls. With fewer than 100 boys and girls in the 4-5-year age group, only
      very few persons were responsible for the high intake. The conversion of nitrate
      to nitrite in the saliva and the degradation of nitrite during production and
      storage must also be considered when evaluating the intake of nitrite.

PMID- 18608492
TI  - Approaches to the evaluation of matrix effects in the liquid chromatography-mass
      spectrometry (LC-MS) analysis of three regulated lipophilic toxin groups in
      mussel matrix (Mytilus edulis).
AB  - Liquid chromatography coupled to mass spectrometry (LC-MS) is seen as an integral
      part of methods of choice for the replacement of animal tests in the
      determination of lipophilic shellfish toxins. However, these techniques are prone
      to matrix effects that need to be considered when developing and validating
      methods. The analysis of shellfish is a challenging task due to the complexity of
      the shellfish matrix and the number of shellfish species encountered in
      monitoring laboratories. Therefore, it is crucial that the cause and the extent
      of matrix effects is fully understood in order to apply corrective measures to
      the analytical method and to develop efficient sample clean-up steps. This paper
      presents different approaches to evaluate matrix effects associated with the
      analysis of okadaic acid (OA), azaspiracid-1 (AZA1) and pectenotoxin-2 (PTX2) in
      cooked and raw mussel flesh. Post-extraction addition and standard addition
      experiments were carried out and analysed using various LC-MS methods. Gradient
      and isocratic elution were compared and ultra-performance liquid chromatography
      (UPLC), using C8 and C18 Acquity BEH columns, was evaluated for the extent of
      matrix effects. When matrix effects were observed, OA and PTX2 were always prone
      to signal enhancement and AZA1 to signal suppression. For all the toxins studied,
      matrix effects were dependent on chromatographic conditions. UPLC separation
      using a C8 column significantly reduced matrix effects compared to the other
      conditions assessed. Furthermore, sample dilution has proven to be an efficient
      way of reducing matrix effects associated with OA analysis.

PMID- 18608493
TI  - Migration of lactic acid, lactide and oligomers from polylactide food-contact
      materials.
AB  - Polylactide (PLA) is used for manufacturing lunch boxes and for packaging fresh
      food in Japan. PLA can be hydrolysed relatively easily to produce lactic acid,
      lactide and oligomers. Different types of PLA sheet were subjected to migration
      tests under various conditions and the lactic acid, lactide and oligomers
      contents of the migration solutions were determined using liquid
      chromatography/mass spectrometry (LC/MS). Furthermore, the change in molecular
      weight was determined by a migration test. PLA was stable at 40 degrees C for 180
      days; the total of lactic acid, lactide and oligomers migration levels were 0.28
      15.00 microg cm(-2). PLA decomposed clearly at 60 degrees C for only 10 days, the
      total migration levels were increased to 0.73-2840 microg cm(-2). PLA sheets with
      a high D-lactic acid content decomposed particularly rapidly. The amounts of
      alkali decomposition products, based on the conversion of lactide and oligomers
      to lactic acid by alkali hydrolysis, corresponded with the total migration
      levels.

PMID- 18608494
TI  - Copper in foods, beverages and waters from South East Spain: influencing factors
      and daily dietary intake by the Andalusian population.
AB  - The copper content of 225 food, 49 beverage and twelve potable water samples were
      determined using atomic absorption spectrometry (AAS). Analyses of NIST and BCR
      reference materials demonstrated the accuracy of this technique. The highest
      copper levels were found in dried fruit and legumes, followed by organ meats,
      molluscs and crustaceans, cephalopods, cereals and sausages, respectively. In
      cereals, legumes and fruit, copper levels increased significantly with increasing
      levels of protein and decreasing carbohydrate content (p < 0.001). In meat and
      meat by-products, copper concentrations found in organ meats were significantly
      higher (p < 0.01). In fresh fish products, copper levels in shellfish were
      significantly higher than those measured in fish (p < 0.001). In vegetables, the
      copper concentrations found in mushrooms were significantly higher (p < 0.005).
      Mean copper concentrations analysed in cheese were statistically higher than
      those determined in other dairy products (p < 0.01). In beverages, copper levels
      determined in rum and juices were significantly higher (p < 0.001). Beverages for
      which a vegetable component was directly used in their manufacturing process
      (juices, wines and beers) had statistically higher copper levels when compared
      with fresh drinks. The daily dietary intake (DDI) of copper in the Andalusian
      diet was 1979 mug day(-1) per person. Cereals, meat, meat by-products and
      vegetables are the food categories that are the main source of copper in the
      daily diet. Taking into account the dietary reference intakes and upper levels
      (900 and 10, 000 mug Cu day(-1) for healthy adults, respectively), the mean
      copper DDI found indicate that for most of healthy adult individuals from the
      area, no adverse effects occur in relation to copper nutrition (deficiency or
      toxicity). Potable waters supplied 53 mug day(-1), which constitutes on average
      0.025% of the maximum tolerable daily intake of this element set by the Joint
      FAO/WHO Expert Committee.

PMID- 18608495
TI  - Contaminants and microorganisms in Dutch organic food products: a comparison with
      conventional products.
AB  - Organic products were analysed for the presence of contaminants, microorganisms
      and antibiotic resistance and compared with those from conventional products. No
      differences were observed in the Fusarium toxins deoxynivalenol and zearalenone
      in organic and conventional wheat, during both a dry period and a very wet period
      which promoted the production of these toxins. Nitrate levels in head lettuce
      produced organically in the open field were much lower than those in conventional
      products. In iceberg lettuce and head lettuce from the greenhouse, no differences
      were detected. Organically produced carrots contained higher nitrate levels than
      conventional products. Both organic and conventional products contained no
      residues of non-polar pesticides above the legal limits, although some were
      detected in conventional lettuce. Organic products contained no elevated levels
      of heavy metals. Salmonella was detected in 30% of pig faeces samples obtained
      from 30 organic farms, similar to the incidence at conventional farms. At farms
      that switched to organic production more then 6 years ago no Salmonella was
      detected, with the exception of one stable with young pigs recently purchased
      from another farm. No Salmonella was detected in faeces at the nine farms with
      organic broilers, and at one out of ten farms with laying hens. This is
      comparable with conventional farms where the incidence for Salmonella lies around
      10%. Campylobacter was detected in faeces at all organic broiler farms, being
      much higher than at conventional farms. One of the most remarkable results was
      the fact that faeces from organic pigs and broilers showed a much lower incidence
      of antibiotic resistant bacteria, except for Campylobacter in broilers. It is
      concluded that the organic products investigated scored as equally well as
      conventional products with regard to food safety and at the same time show some
      promising features with respect to antibiotic resistance.

PMID- 18608496
TI  - Acrylamide-asparagine relationship in baked/toasted wheat and rye breads.
AB  - Acrylamide in baked and toasted wheat and rye bread was studied in relation to
      levels of asparagine in flour, dough, bread and toasts. Asparagine was consumed
      during bread preparation resulting in reduced acrylamide content in the products.
      In wheat bread, 12% of the asparagine initially present in the flour (0.14 g kg(
      1)) remained after yeast fermentation and baking; for rye bread, 82% of
      asparagine remained after sourdough fermentation and baking. Asparagine present
      in untoasted wheat bread had totally reacted after hard toasting. Toasted wheat
      and rye bread slices contained 11-161 and 27-205 microg kg(-1) acrylamide,
      respectively, compared to untoasted wheat and rye bread with <5 and 7-23 microg
      kg(-1) acrylamide, respectively. The dietary intake of acrylamide from bread
      (untoasted) of 2 microg day(-1) is relatively low; however, acrylamide exposure
      from bread increases several fold for people eating toasted bread.

PMID- 18608497
TI  - Assessment of dietary exposure of nitrate and nitrite in France.
AB  - The aim of this study was to assess the dietary exposure of nitrate and nitrite
      in France. A total of 13, 657 concentration levels of nitrate and nitrite
      measured in food, representing 138 and 109 food items, respectively, and coming
      from French monitoring programmes between 2000 and 2006, were used. Depending on
      the non-detected and non-quantified analysis treatment, lower and upper
      concentration mean estimates were calculated for each food item. These were
      combined with consumption data derived from 1474 adults and 1018 children from
      the French national individual consumption survey (INCA1), conducted in 1999 and
      based on a 7-day food record diary. A total of 18% of spinaches, 6% of salads,
      10% of cheeses, 8% of meat products and 6% of industrial meat products exceeded
      the European nitrate maximum level or maximum residual level. A total of 0.4% of
      industrial meat products and 0.2% of meat products exceeded their European
      nitrite maximum level or maximum residual level. Nitrate dietary exposure
      averaged 40% of the acceptable daily intake (ADI; 3.7 mg kg(-1) body weight day(
      1)) for adults and 51 - 54% of the ADI for children with the major contributors
      being, for adults and children, respectively, vegetables (24 and 27% of ADI),
      potatoes (5 and 11% of ADI), and water (5 and 5% of ADI). The individual nitrate
      dietary intake of 1.4% (confidence interval (CI(95th)) [0.8; 2.0]) to 1.5%
      (CI(95th) [0.9; 2.1]) of adults and 7.9% (CI(95th) [6.2; 9.6]) to 8.4% (CI(95th)
      [6.7; 10.1]) of children were higher than the ADI. Nitrite dietary exposure
      averaged 33-67% of the ADI (0.06 mg kg(-1) body weight day(-1)) for adults and 67
      133% of the ADI for children, with contributions of additive food vectors at 33%
      of ADI for adults and 50-67% of ADI for children. The individual nitrite dietary
      intake of 0.7% (CI(95th) [0.3; 1.1]) to 16.4% (CI(95th) [14.5; 18.3]) of adults
      and 10.5% (CI(95th) [8.6; 12.4]) to 66.2% (CI(95th) [63.3; 69.1]) of children
      were higher than the ADI.

PMID- 18608498
TI  - Optimization of microwave-assisted extraction with saponification (MAES) for the
      determination of polybrominated flame retardants in aquaculture samples.
AB  - The efficiency of microwave-assisted extraction with saponification (MAES) for
      the determination of seven polybrominated flame retardants (polybrominated
      biphenyls, PBBs; and polybrominated diphenyl ethers, PBDEs) in aquaculture
      samples is described and compared with microwave-assisted extraction (MAE).
      Chemometric techniques based on experimental designs and desirability functions
      were used for simultaneous optimization of the operational parameters used in
      both MAES and MAE processes. Application of MAES to this group of contaminants in
      aquaculture samples, which had not been previously applied to this type of
      analytes, was shown to be superior to MAE in terms of extraction efficiency,
      extraction time and lipid content extracted from complex matrices (0.7% as
      against 18.0% for MAE extracts). PBBs and PBDEs were determined by gas
      chromatography with micro-electron capture detection (GC-muECD). The
      quantification limits for the analytes were 40-750 pg g(-1) (except for BB-15,
      which was 1.43 ng g(-1)). Precision for MAES-GC-muECD (%RSD < 11%) was
      significantly better than for MAE-GC-muECD (%RSD < 20%). The accuracy of both
      optimized methods was satisfactorily demonstrated by analysis of appropriate
      certified reference material (CRM), WMF-01.

PMID- 18608499
TI  - Determination of polybromodiphenyl ethers (PBDEs) in milk cream by gas
      chromatography-mass spectrometry.
AB  - An analytical method for polybromodiphenyl ethers (PBDEs) in milk cream has been
      optimized. The six PBDEs targeted were chosen on criteria of toxicity and
      occurrence in environmental matrices. Three methods of extraction were tested and
      compared in terms of lipid recovery yields and repeatability. The sample
      preparation process includes two steps: extraction by accelerated solvent
      extraction (ASE) and purification by solid phase extraction (SPE). The preferred
      method of extraction used a hexane/methylene chloride/methanol (5 : 2 : 1, v/v)
      solvent mixture. Three extraction cycles were carried out per sample at a
      temperature of 80 degrees C and a pressure of 1500 psi. The method was validated
      on milk cream samples spiked with the specified PBDEs. Recoveries for the whole
      sample preparation process (extraction and cleanup) for cream samples spiked at
      10 and 100 ng g(-1) were greater than 80% (ranging from 81 to 106%) at both
      concentrations for BDE-99, -100, -153 and 154. Recoveries were lower (ranging
      from 65 to 75%) for BDE-28 and BDE-47. PBDEs were quantified by GC/MS detection
      with selected ion monitoring (SIM) using three ions formed by electron capture.
      The method was successfully tested on real samples.

PMID- 18608501
TI  - Determination of preservatives in meat products by flow injection analysis (FIA).
AB  - Various preservatives are added to meat products to extend shelf-life and enhance
      food safety; thus, their determination is essential for legislative purposes and
      consumer health. Analytical methodologies based on flow injection analysis (FIA)
      offer attractive advantages compared with other procedures, such as versatility,
      precision, low cost, speed and ease of automation. This review considers the
      status of published FIA methodologies for the determination of preservatives in
      meat products. The techniques are described regarding their application to
      different preservatives (nitrates and nitrites, sulfites, sorbates, benzoates and
      p-hydroxybenzoate esters), with emphasis on extraction, separation, detection and
      quantification procedures in meat matrices.

PMID- 18608502
TI  - Evaluation of atoxigenic isolates of Aspergillus flavus as potential biocontrol
      agents for aflatoxin in maize.
AB  - Aflatoxin contamination resulting from maize infection by Aspergillus flavus is
      both an economic and a public health concern. Therefore, strategies for
      controlling aflatoxin contamination in maize are being investigated. The
      abilities of eleven naturally occurring atoxigenic isolates in Nigeria to reduce
      aflatoxin contamination in maize were evaluated in grain competition experiments
      and in field studies during the 2005 and 2006 growing seasons. Treatments
      consisted of inoculation of either grains in vials or ears at mid-silking stage
      in field plots, with the toxigenic isolate (La3228) or atoxigenic isolate alone
      and co-inoculation of each atoxigenic isolate and La3328. Aflatoxin B(1) + B(2)
      concentrations were significantly (p < 0.05) lower in the co-inoculation
      treatments compared with the treatment in which the aflatoxin-producing isolate
      La3228 was inoculated alone. Relative levels of aflatoxin B(1) + B(2) reduction
      ranged from 70.1% to 99.9%. Among the atoxigenics, two isolates from Lafia,
      La3279 and La3303, were most effective at reducing aflatoxin B(1) + B(2)
      concentrations in both laboratory and field trials. These two isolates have
      potential value as agents for the biocontrol of aflatoxin contamination in maize.
      Because these isolates are endemic to West Africa, they are both more likely than
      introduced isolates to be well adapted to West African environments and to meet
      regulatory concerns over their use throughout that region.

PMID- 18608503
TI  - Preparation of [13C3]-melamine and [13C3]-cyanuric acid and their application to
      the analysis of melamine and cyanuric acid in meat and pet food using liquid
      chromatography-tandem mass spectrometry.
AB  - For the determination of melamine and cyanuric acid the labelled internal
      standards [(13)C(3)]-melamine and [(13)C(3)]-cyanuric acid were synthesized using
      the common substrate [(13)C(3)]-cyanuric chloride by reaction with ammonia and
      acidified water, respectively. Standards with excellent isotopic and chemical
      purities were obtained in acceptable yields. These compounds were used to develop
      an isotope dilution liquid chromatography/mass spectrometry (LC/MS) method to
      determine melamine and cyanuric acid in catfish, pork, chicken, and pet food. The
      method involved extraction into aqueous methanol, liquid-liquid extraction and
      ion exchange solid phase clean-up, with normal phase high-performance liquid
      chromatography (HPLC) in the so-called hydrophilic interaction mode. The method
      had a limit of detection (LOD) of 10 microg kg(-1) for both melamine and cyanuric
      acid in the four foods with a percentage coefficient of variation (CV) of less
      than 10%. The recovery of the method at this level was in the range of 87-110%
      and 96-110% for melamine and cyanuric acid, respectively.

PMID- 18608504
TI  - Comprehensive molecular system to study the presence, growth and ochratoxin A
      biosynthesis of Penicillium verrucosum in wheat.
AB  - Based on the sequence of the ochratoxin A polyketide synthase gene (otapksPV), a
      polymerase chain reaction (PCR) system for the specific detection of Penicillium
      verrucosum in wheat has been developed. In a further approach, a real-time PCR
      system has been applied to determine the growth kinetics of P. verrucosum in
      wheat at cell numbers above 10(3) colony-forming units (cfu) ml(-1). The data
      obtained by real-time PCR correlated well with the data obtained by the plate
      count technique. For this purpose, the DNA was isolated directly from
      contaminated wheat without any further enrichment step. In a reverse
      transcriptase real-time PCR, the expression of the otapksPV gene in wheat was
      detected 22 days after inoculation and storage at ambient temperature. Reasonable
      amounts of ochratoxin A, however, could not be detected before day 30. This early
      activation of ochratoxin A related genes was confirmed by microarray analysis.

PMID- 18608507
TI  - Comparison of calibration methods for the quantification of Basmati and non
      Basmati rice using microsatellite analysis.
AB  - The accurate quantification of non-Basmati rice in Basmati rice is central to the
      successful prosecution of adulteration, where non-Basmati rice has been
      substituted for Basmati rice. The current method and three alternatives of
      constructing calibration curves for the measurement of non-Basmati rice in
      Basmati rice using microsatellite analysis were investigated. The methods
      compared involved power regression, linear regression (with and without log(10)
      transformation) and hyperbolic regression of the ratio of Basmati to non-Basmati
      peak areas. Assessments were made using error uncertainty, standard error at the
      agreed limit of adulteration, and 95% confidence intervals for five example data
      sets. The linear regression of the ratio of peak areas to the ratio of content
      proportions was found to give the most precise calibration and thus enhanced
      quantification of the level of adulteration of Basmati rice with non-Basmati
      rice.

PMID- 18608508
TI  - Liquid chromatographic analysis of maneb and its main degradation product,
      ethylenethiouera, in fruit juice.
AB  - Ethylenethiourea (ETU), a possible human carcinogen and an antithyroid compound,
      is the main degradation product of the fungicide, maneb, which is widely used in
      agriculture. In this study, a rapid and accurate method for the determination of
      maneb and ETU in various fruit juices (tomato, grape and apple) was developed
      requiring minimal clean-up of sample extract, no derivatization prior to
      injection and no specialized LC detectors. Samples were cleaned up using silica
      and octadecylsilica (C18) cartridges before injection into liquid chromatography
      (LC) with diode-array detection (DAD). Recoveries ranged between 90 and 101% with
      relative standard deviations from 0.7 to 3.8%. The limits of determination of
      maneb and ETU were 0.1 and 0.01 mg l(-1), respectively. The proposed method was
      used to monitor the presence of maneb and ETU in commercial samples taken from
      different markets of Istanbul, Turkey. Maneb was found in one tomato juice sample
      at a concentration of 0.45 mg l(-1) but ETU was below the LOQ. Two tomato juices
      had no detectable maneb residue but contained ETU at levels of 0.08 and 0.11 mg l
      (1).

PMID- 18608510
TI  - Monoclonal-based enzyme-linked immunosorbent assay for the detection of
      zearalenone in cereals.
AB  - A monoclonal antibody against zearalenone (ZEA) was produced and used
      successfully to develop a direct competitive enzyme-linked immunosorbent assay
      (DC-ELISA) for the analysis of ZEA in cereals. This DC-ELISA had a limit of
      detection of 0.15 +/- 0.02 microg l(-1) and an IC50 value of 1.13 +/- 0.16 microg
      l(-1). Matrix interference was minimized by dilution of the sample extract before
      ELISA assays. Aqueous methanol (80%) gave good extraction efficiencies, and the
      recovery from spiked rice, barley, and corn samples averaged between 87 and 112%.
      Although ZEA was detected in seven (9%) of 80 rice samples and in eight (16%) of
      50 barley samples, the concentration of ZEA in samples was around or below the
      limit of detection of DC-ELISA. Among 38 corn samples, ZEA was detected in nine
      (24%) samples in the range 41.0-909.8 microg kg(-1). Re-analysis of the ELISA
      positive corn samples by high-performance liquid chromatography (HPLC) confirmed
      that seven (18%) corn samples were positive. The ZEA results for corn showed very
      good agreement between DC-ELISA and a commercial AgraQant zearalenone kit (r2 =
      0.98). Thus, the monoclonal antibody-based DC-ELISA could be applied to the
      preliminary screening of ZEA contamination when analysis of a large sample number
      is needed.

PMID- 18608511
TI  - Role of epidemiology in microbial risk assessment.
AB  - Microbial risk assessment (MRA) is a systematic tool to evaluate the likelihood
      of exposure to food-borne pathogens and the resulting impact of exposure on
      consumer health. In addition, MRA can be used to evaluate the public health
      impact of intervention or control measures designed to prevent or reduce
      pathogens at any or all of the steps in our complex food production system.
      Epidemiological studies provide useful information and data for MRA. This paper
      discusses the use and limitations of epidemiological data in the development and
      validation of MRA using examples from published microbial risk assessments.

PMID- 18608512
TI  - In-house validation of an ELISA method for screening of semicarbazide in eggs.
AB  - An enzyme-linked immunosorbent assay (ELISA) method is described for the semi
      quantitative determination of semicarbazide (SEM), the marker residue for the
      banned nitrofuran drug, nitrofurazone, in chicken eggs. The sample homogenate is
      subjected to acid hydrolysis and derivatisation with o-nitrobenzaldehyde,
      followed by ethyl acetate/hexane extraction and detection by ELISA. The ELISA
      procedure has been validated using 0.3, 1.0 and 3 microg kg(-1) of SEM in
      fortified samples. Detection capability (CC(ss)) was based on the acceptance of
      5% false compliant results for a given concentration level according to
      Commission Decision 2002/657/EC and was determined to be 0.3 microg kg(-1) with a
      respective limit of detection of 0.13 microg kg(-1). A validated LC-MS/MS method
      was used for the analysis of incurred egg samples and the results compared with
      ELISA. A good correlation between the results obtained from ELISA and LC-MS/MS
      within the concentration range 0.12-20.3 microg kg(-1) was observed in samples
      collected from chickens fed with a medicated ration of nitrofurazone (r = 0.992,
      n = 14). Validated ELISA enabled reliable monitoring of SEM levels in eggs
      collected from incurred chickens over a 90-day period.

PMID- 18608514
TI  - Molecular techniques for the detection of granary weevil (Sitophilus granarius
      L.) in wheat and flour.
AB  - The granary weevil (Sitophilus granarius L.) is a stored grain pest that causes
      major economic losses. It reduces the quantity and quality of the grain by its
      feeding and excretion. Sequences of S. granarius mitochondrial cytochrome oxidase
      subunits genes mtCOI and mtCOII were analysed and compared with mtCOI/II
      sequences available in GenBank. The analysed genes displayed a high level of
      homology between corresponding subunits. Attempts were undertaken to develop
      detection methods for contamination by S. granarius in wheat and wheat flour
      based on the molecular biology techniques: standard and real-time polymerase
      chain reaction (PCR) with a TaqMan molecular probe. (TaqMan probes are dual
      labelled hydrolysis probes) Specific primers designed based on available
      sequences for mtCOI and mtCOII genes were applied and optimal reaction conditions
      established. The specificity of both methods was studied by using a species
      closely related to S. granarius: S. oryzae and S. zeamais. It is shown that the
      sensitivity threshold was very high - we were able to detect the equivalent of
      one beetle per 100 kg of flour when the real-time PCR with TaqMan probe method
      was applied to model samples. The primer sets used turned out to be species
      specific, and the technique was rapid, reliable and very sensitive.

PMID- 18608515
TI  - Migration measurement and modelling from poly(ethylene terephthalate) (PET) into
      soft drinks and fruit juices in comparison with food simulants.
AB  - Poly(ethylene terephthalate) (PET) bottles are widely used for beverages.
      Knowledge about the migration of organic compounds from the PET bottle wall into
      contact media is of interest especially when post-consumer recyclates are
      introduced into new PET bottles. Using migration theory, the migration of a
      compound can be calculated if the concentration in the bottle wall is known. On
      the other hand, for any given specific migration limit or maximum target
      concentration for organic chemical compounds in the bottled foodstuffs, the
      maximum allowable concentrations in the polymer CP,0 can be calculated. Since a
      food simulant cannot exactly simulate the real migration into the foodstuff or
      beverages, a worse-case simulation behaviour is the intention. However, if the
      migration calculation should not be too overestimative, the polymer-specific
      kinetic parameter for migration modelling, the so-called AP value, should be
      established appropriately. One objective of the study was the kinetic
      determination of the specific migration behaviour of low molecular weight
      compounds such as solvents with relatively high diffusion rates and, therefore,
      with high migration potential from the PET bottle wall into food simulants in
      comparison with real beverages. For this purpose, model contaminants were
      introduced into the bottle wall during pre-form production. The volatile
      compounds toluene and chlorobenzene were established at concentrations from about
      20-30 mg kg(-1) to 300-350 mg kg(-1). Phenyl cyclohexane was present at
      concentrations of 35, 262 and 782 mg kg(-1), respectively. The low volatile
      compounds benzophenone and methyl stearate have bottle wall concentrations of
      about 100 mg kg(-1) in the low spiking level up to about 1000 mg kg(-1) in the
      highly spiked test bottle. From these experimental data, the polymer specific
      parameters (AP values) from mathematical migration modelling were derived. The
      experimental determined diffusing coefficients were determined, calculated and
      compared with literature data and an AP' value of 1.0 was derived thereof for non
      swelling food simulants like 3% acetic acid, 10% ethanol or iso-octane. For more
      swelling condition, e.g. 95% ethanol as food simulant, an AP' value of 3.1 seems
      to be suitable for migration calculation. In relation to PET recycling safety
      aspects, maximum concentrations in the bottle wall were established for
      migrants/contaminants with different molecular weights, which correspond with a
      migration limit of 10 microg kg(-1). From the experimental data obtained using
      food simulants and in comparison with beverages, the most appropriate food
      simulant for PET packed foods with a sufficient but not too overestimative worse
      case character was found to be 50% ethanol. In addition, it can be shown that
      mass transport from PET is generally controlled by the very low diffusion in the
      polymer and, as a consequence, partitioning coefficients (KP/F values) of
      migrants between the polymer material and the foodstuff do not influence the
      migration levels significantly. An important consequence is that migration levels
      from PET food-contact materials are largely independent from the nature of the
      packed food, which on the other hand simplifies exposure estimations from PET.

PMID- 18608516
TI  - Early lipoic acid intake protects retina of diabetic mice.
AB  - The aim of this study was to test the effect of lipoic acid treatment on the
      retina after a short diabetic insult. Diabetes was induced by alloxan and mice
      were divided into sub-groups; control, diabetic, diabetic+insulin and all groups
      received+/-lipoic acid (100 mg/kg body weight) for 3 weeks. GSH content, MDA
      concentration, GPx activity were measured and electroretinograms (ERG) were
      recorded. Early administration of lipoic acid to diabetic mice prevented the
      statistically significant decreases of GSH content and GPx activity and
      normalized MDA concentration. Moreover, lipoic acid restored electroretinogram b
      wave amplitude of diabetic animals to control values. Lipoic acid has a
      protective effect on the diabetic retina.

PMID- 18608517
TI  - Proinflammatory cytokine-induced cellular senescence of biliary epithelial cells
      is mediated via oxidative stress and activation of ATM pathway: a culture study.
AB  - Cellular senescence is reportedly involved in cholangiopathy in primary biliary
      cirrhosis and oxidative stress is proposed as a pathogenetic factor in biliary
      epithelial cells (BECs). This study investigated the involvement of
      proinflammatory cytokines (IFN-beta, IFN-gamma and TNF-alpha) and ataxia
      telangiectasia-mutated (ATM)/p53/ p21(WAF1/Cip1) pathway with respect to
      oxidative stress in cellular senescence of BECs. H(2)O(2) treatment (oxidative
      stress) induced phosphorylation (activation) of ATM and p53 and also
      p21(WAF1/Cip1) expression in BECs. Treatment with inflammatory cytokines
      generated reactive oxygen species (ROS) in cultured BECs followed by activation
      of the ATM/p53/p21(WAF1/Cip1) pathway and the induction of cellular senescence.
      Pre-treatment with ATM inhibitor (2-aminopurine) and antioxidant (N
      acetylcysteine) significantly blocked the cellular senescence of BECs induced by
      oxidative stress or inflammatory cytokines. In conclusion, proinflammatory
      cytokines induce ROS generation and activate the ATM/p53/p21(WAF1/Cip1) pathway,
      followed by biliary epithelial senescence. This senescent process may be involved
      in the development of destructive cholangiopathy in humans.

PMID- 18608522
TI  - Effects of metformin and ethinyl estradiol-cyproterone acetate on clinical,
      endocrine and metabolic factors in women with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a major endocrine abnormality
      that affects women of reproductive age. Oral contraceptive pills are usually the
      first choice of treatment for PCOS when fertility is not desired. Metformin, an
      insulin-sensitizing drug, has been shown to improve such metabolic abnormality.
      Aim. To compare the effects of a contraceptive pill in combination with metformin
      on the clinical, endocrine and metabolic parameters in obese and non-obese
      patients with PCOS. METHODS: Sixty PCOS patients (25 obese, 35 non-obese) were
      enrolled in this prospective clinical study. PCOS was defined according to the
      Rotterdam criteria. Patients were randomized to oral treatment with Diane35 (35
      microg ethinyl estradiol plus 2 mg cyproterone acetate), metformin or a
      combination of Diane35/metformin for 3 months. Body mass index (BMI), waist-to
      hip ratio (WHR), Ferriman-Gallwey (FG) score, leuteinizing hormone (LH), follicle
      stimulating hormone (FSH), testosterone, fasting insulin and glucose/insulin
      ratio were measured at baseline and at the end of treatment. RESULTS: Diane35
      resulted in a higher reduction of FG score in both obese and non-obese PCOS
      patients compared with metformin. Menstrual regularity was restored in all PCOS
      patients treated with Diane35 compared with only 28% of those receiving
      metformin. Metformin significantly decreased BMI and WHR in obese patients (p <
      0.05). Testosterone levels decreased in all three groups. LH levels and LH/FSH
      ratio decreased with Diane35 and Diane35/metformin in both obese and non-obese
      patients. Metformin significantly decreased fasting insulin concentrations (p <
      0.05 and p < 0.01) and increased the insulin sensitivity (p < 0.05) in both obese
      and non-obese PCOS patients, while no significant changes were observed in the
      Diane35 group. In addition, insulin levels also decreased (p < 0.05) in the
      Diane35/metformin group. CONCLUSIONS: Our data show that a combination of
      metformin and contraceptive pill may be more effective in suppressing the
      hyperandrogenemia of obese and non-obese PCOS patients than metformin alone and
      may reduce insulin levels more than contraceptive pill alone. Hence, combined
      treatment may become a more effective therapeutic option for PCOS.

PMID- 18608518
TI  - An SOD mimic protects NADP+-dependent isocitrate dehydrogenase against oxidative
      inactivation.
AB  - The isocitrate dehydrogenases (ICDs) catalyse the oxidative decarboxylation of
      isocitrate to alpha-ketoglutarate and can use either NAD(+) or NADP(+) as a
      cofactor. Recent studies demonstrate that the NADP(+)-dependent isocitrate
      dehydrogenase, as a source of electrons for cellular antioxidants, is important
      for protection against oxidative damage. ICD, however, is susceptible to
      oxidative inactivation, which in turn compromises cellular antioxidant defense.
      This study investigates the effect of a superoxide dismutase (SOD) mimic, MnTM-2
      PyP(5+), on the inactivation of NADP(+)-dependent ICD in SOD-deficient
      Escherichia coli and in diabetic rats. The findings show that E. coli ICD is
      inactivated by superoxide, but the inactivated enzyme is replaced by de novo
      protein synthesis. Statistically significant decrease of ICD activity was found
      in the hearts of diabetic rats. MnTM-2-PyP(5+) protected ICD in both models.

PMID- 18608524
TI  - The impact of commonly prescribed drugs on male fertility.
AB  - To analyze the impact of commonly used drugs on male fertility, we assessed the
      clinical characteristics of patients with impaired semen quality while they were
      taking medication for chronic diseases and after switching therapies. Of 1768
      infertile males, 201 patients were taking medications and had impaired semen
      quality without any seminal tract obstruction, spermatogenic abnormalities or
      hypogonadotropic hypogonadism. Of these 201 men, a total of 165 had no history of
      testicular diseases nor abnormalities in any examinations. Amongst them, H1
      receptor antagonists were the most common medication taken, followed by
      antiepileptics and antibiotics. They were divided into two groups: an
      intervention group (73 patients), who could stop or switch their medications, and
      a control group (92 patients), who could not. In the intervention group, semen
      quality improvement rate and conception rate (93% and 85%, respectively) were
      much higher than those of the control group (12% and 10%, respectively). After
      switching therapies, the time interval before conception was 7.3 months, which
      was significantly shorter in asthenozoospermia than oligozoospermia. Our results
      confirm the potential fertility hazards of commonly used drugs and their
      reversibility. Moreover, after switching medication, drug-induced
      asthenozoospermia was cured more rapidly than oligozoospermia, suggesting that
      further delineation of such differences may help to elucidate mechanisms of
      spermatogenesis and might facilitate the development of non-hormonal male
      contraceptive agents.

PMID- 18608525
TI  - Working Party on Sperm Donation Services in the UK: report and recommendations.

PMID- 18608528
TI  - Immunomodulatory activity of synthetic triterpenoids: inhibition of lymphocyte
      proliferation, cell-mediated cytotoxicity, and cytokine gene expression through
      suppression of NF-kappaB.
AB  - Synthetic oleanane triterpenoids (CDDO, CDDO-Im and CDDO-Me) are potent anti
      inflammatory agents, but have not been investigated for effects on T cell
      mediated immune responses. Here we demonstrate that CDDOs have profound
      immunosuppressive effects on T cell proliferation, development of IL-2 activated
      LAK cells and cytotoxic T lymphocytes (CTLs), and expression of cytokines at
      concentrations of 1.25 microM to 0.078 microM. Treatment with CDDO-Me also
      inhibited the generation of allo-reactive T cell responses in vivo. The
      suppression of these cell-mediated immune responses by CDDO-Me was associated
      with the inhibition of NF-kappaB transcription factor.

PMID- 18608529
TI  - Expression of proto-oncogene C-kit and correlation with morphological evaluations
      in canine cutaneous mast cell tumors.
AB  - Canine cutaneous mast cell tumor (MCT) is very common disease in dogs, this is
      more aggressive than in other species. The biologic behavior of MCT is highly
      variable and a more accurate prognosis for these tumors needs to performed. The
      proto-oncogene c-kit is known to play a critical role in development and function
      of mast cells (MC). The aim of this study was to evaluate the expression of
      immunohistochemical pattern of c-kit in MCTs and to correlate these results with
      MC density (MCD) and intratumoral microvessel density (MVD). Our results confirm
      that a more aggressive biologic behavior of canine MCT is associated with the
      increased c-kit expression, further suggesting a new role for c-kit, as a useful
      marker, in diagnostic pathology and in tumor progression.

PMID- 18608530
TI  - Effect of rifampicin to inhibit rapamycin-induced autophagy via the suppression
      of protein phosphatase 2A activity.
AB  - Recently, a number of studies have focused on the secondary effects of
      rifampicin. In the present study, we assessed whether rifampicin influences the
      rapamycin-induced autophagy of RAW 264.7 cells. Here, we demonstrate that the
      rapamycin-induced autophagy is dependent on protein phosphatase (PP) 2A activity
      and rifampicin inhibits the activity of PP2A by reducing expressions of PP2A
      subunits A and C. In addition, rifampicin slightly, but significantly, inhibited
      the rapamycin-induced dephosphorylation of p70 ribosomal protein S6 kinase
      (p70S6K) at Thr421/Ser424, which are regulated dually by both rapamycin and PP2A,
      but not at the rapamycin dephosphorylation site located at Thr389. These results
      show that rifampicin inhibits rapamycin-induced autophagy, at least in part, via
      the suppression of PP2A activity.

PMID- 18608531
TI  - Unilateral and bilateral cochlear implants and the implant-plus-hearing-aid
      profile: comparing self-assessed and measured abilities.
AB  - Patients fitted with one (CI) versus two (CI+CI) cochlear implants, and those
      fitted with one implant who retain a hearing aid in the non-implanted ear
      (CI+HA), were compared using the speech, spatial, and qualities of hearing scale
      (SSQ) (Gatehouse & Noble, 2004). The CI+CI profile yielded significantly higher
      ability ratings than the CI profile in the spatial hearing domain, and on most
      aspects of other qualities of hearing (segregation, naturalness, and listening
      effort). A subset of patients completed the SSQ prior to implantation, and the
      CI+CI profile showed consistently greater improvement than the CI profile across
      all domains. Patients in the CI+HA group self-rated no differently from the CI
      group, post-implant. Measured speech perception and localization performance
      showed some parallels with the self-rating outcomes. Overall, a unilateral CI
      provided significant benefit across most hearing functions reflected in the SSQ.
      Bilateral implantation offered further benefit across a substantial range of
      those functions.

PMID- 18608532
TI  - Maturation of bone conduction multiple auditory steady-state responses.
AB  - The objective of this study was to compare bone-conduction (BC) auditory steady
      state responses (ASSR) for infants and adults with normal hearing to investigate
      the time course of maturation of BC hearing sensitivity. Bone-conduction multiple
      ASSRs were recorded in 0-11-month-old (n=35), and 12-24-month-old infants (n=13),
      and adults (n=18). Low-frequency BC ASSR thresholds increased with age, whereas,
      high-frequency ASSR thresholds were unaffected by age except for a slight
      improvement at 2000 Hz. Compared to adults, BC ASSR amplitudes for young infants
      were larger for low frequencies, whereas, their amplitudes were smaller or
      similar for high frequencies. Compared to adults, young infants are much more
      sensitive to low-frequency BC stimuli, and probably more sensitive to high
      frequency BC stimuli; these differences between infants and adults persist until
      at least two years of age. Different 'normal levels' for infants of different
      ages must be used and are proposed in this study.

PMID- 18608533
TI  - Hearing status among commercial pilots in a Swedish airline company.
AB  - The aim was to study hearing impairment in commercial pilots. A total of 634 male
      and 30 female pilots (N=664) in a Swedish airline company underwent repeated
      audiological tests during the period 1974-2005. The last test was used to study
      hearing impairment. The mean values for the hearing test at 3, 4, and 6 kHz were
      used for the ear with worse hearing impairment. Data was compared with a general
      adult Swedish population (n=603) not occupationally exposed to noise. Equivalent
      noise levels gate to gate (Leq) were measured in the cockpit of different
      aircraft. Leq was 75-81 dB (A), peak exposures were 105 dB (A) from the cabin
      call signal. Median values were similar as in the reference group at all ages.
      There was no association between years of employment, tobacco smoking, and
      hearing impairment, when adjusted for age and gender by multiple logistic
      regressions analysis. In conclusion, pilots are exposed to equivalent noise
      levels below the current Swedish occupational standard of 85 dB (A), with short
      peak exposures above the standard, and have normal age-matched hearing
      thresholds.

PMID- 18608534
TI  - Composition and safety analysis of Chinese traditional fermented soybean paste
      made by transgenic soybean.
AB  - The traditional Chinese soybean paste was produced by cooked transgenic soybean
      fermentation with the composition of moisture 53%, amino acid 0.84% (calculated
      by nitrogen), votive sugar 6.21% and total acid 1.66%. A number of microorganism
      species were isolated and identified, including fungi and bacteria, and the
      bacterium species Rhizopus oryzae Went and Prinsen Geerligs were dominant in
      transgenic soybean paste. The results showed that the transgenic soybean paste
      contain abundant amino acids and vitamins (vitamin A, 42.87 IU; vitamin B, 10.31
      mg; vitamin B, 20.64 mg; nicotinamide, 2.54 mg; pantothenic acid, 0.63 mg;
      vitamin B, 6,847 microg; folic acid, 105 microg; vitamin B, 123.85 microg; and
      biotin, 56.34 microg). Pathogenic microorganisms were not be detected in the
      transgenic fermented soybean paste.

PMID- 18608535
TI  - Influence of dietary and socio-demographic factors on the iron status of married
      adolescent girls from Indian urban slums.
AB  - To explore the influence of dietary factors of iron bioavailability and socio
      demographic conditions on blood iron status of married adolescent girls (MAG), a
      cross-sectional study was conducted in 173 MAG (15-19 years old) from urban slums
      near Pune city, India. Diet was assessed by two random 24-h recalls. The age,
      weight, height, education, family size, income, physical work, and number of days
      of menstrual loss were recorded. Fasting blood was analyzed for hemoglobin and
      serum ferritin. Mean intakes of micronutrients were 40-75% less than the
      recommended dietary intakes for Indian adolescent girls. High intake of phytates
      (171+/-6 mg/day) and low intakes of vitamin C (25+/-1 mg/day) resulted in low
      bioavailable iron intakes. The mean bioavailable iron intake was 0.76+/-0.3
      mg/day, which is one-half of the basal iron requirement of adolescent girls. The
      prevalence of iron deficiency (serum ferritin<12 microg/l) was 25.1%, and anemia
      (hemoglobin <12 g/l) was seen in 46.4% of MAG. A multiple regression model
      adjusted for energy intake indicated that intakes of beta-carotene and riboflavin
      were associated with hemoglobin (P<0.001) and those of zinc, riboflavin and
      thiamin associated with serum ferritin (P<0.01). Multiple regressions including
      socio-demographic factors revealed that the family size, number of menstrual days
      lost and total bioavailable iron intake were the influencing factors for low iron
      status. In conclusion, there is a need to increase intakes of vitamin C and other
      micronutrients of the MAGs and to improve iron bioavailability through diet
      modifications.

PMID- 18608538
TI  - Normal distribution of urinary polyphenol excretion among Egyptian males 7-14
      years old and changes following nutritional intervention with tomato juice
      (Lycopersicon esculentum).
AB  - BACKGROUND: The urinary flavonoids are considered a reliable biomarker for the
      intake of polyphenol-rich foods. OBJECTIVES: To assess the normal distribution of
      urinary polyphenol [PP] excretion among healthy male children and adolescents on
      a typical Egyptian diet. To follow up the impact of nutritional intervention with
      tomato juice on the urinary excretion of [PP]. SUBJECTS: Forty-nine male subjects
      7-14 years old collected a 24-h urine sample and filled a dietary record during a
      7-day period. A daily serving of 230 g fresh tomato juice was followed for 18
      days in a subgroup. Total urinary [PP] excretions were measured before and after
      termination of the intervention program. The total urinary [PP] was analyzed
      after a clean-up solid-phase extraction step by the Folin-Ciocalteu reagent in
      the 96 micro plates. The results were expressed as gallic acid equivalents (GAE).
      RESULTS: The urinary [PP] excretion averaged 48.6+/-5.5 mg GAE/24 h, equivalent
      to 89.5+/-8.4 mg GAE/g creatinine. The mean urinary [PP] excretion increased
      significantly (P<0.05) following the intervention with tomato juice (287.4+/-64.3
      mg GAE/g creatinine) compared with the respective mean baseline level (94.5+/
      8.92 mg GAE/g creatinine). CONCLUSION: Clinical laboratory reference limits for
      urinary polyphenols are presented for Egyptian male children and adolescents.
      Measuring the urinary polyphenol excretion proved a good biomarker for the
      dietary polyphenol intake and the results demonstrated that tomato [PP] was
      highly bioavailable in the human body.

PMID- 18608539
TI  - Extraction of lycopene from tomato sauce with mushrooms (Agaricus brasiliensis),
      determined by high-performance liquid chromatography.
AB  - Lycopene belongs to the subgroup of non-oxygenated carotenoids with antioxidant
      and anti-carcinogenic properties that are comparatively more powerful than the
      majority of plasma carotenoids. When foodstuffs containing lycopene are
      processed, the cell wall breaks down during the thermal process--thus enabling
      the extraction of lycopene from chromoplasts, improving their bioavailability.
      Edible mushroom Agaricus brasiliensis stands out given its medicinal properties
      and antioxidant potential when used to treat heart diseases and to prevent
      cancer. Given the interest in lycopene-rich foods, the purpose of the present
      study was to determine the lycopene present in different types of tomato sauce
      with A. brasiliensis and/or its extract by high-performance liquid
      chromatography. The type of solvent (dichloromethane, hexane and ethanol) to
      remove water from the tomato sauce was tested before the extraction of
      carotenoids. Lycopene determination in tomato sauces, in tomatoes and in the A.
      brasiliensis extract was carried out via high-performance liquid chromatography.
      Findings show that when tomato sauce and raw materials underwent heat treatment,
      the type of treatment did not interfere with carotenoid and lycopene
      bioavailability--indicating that those sauces have a significant concentration of
      carotenoids and, in particular, their content in the lycopene proportion compared
      with total carotenoids.

PMID- 18608540
TI  - Partial substitution of sodium with potassium in white bread: feasibility and
      bioavailability.
AB  - A high sodium intake, to which bread makes a major contribution, and a low
      potassium intake are believed to be important factors in the promotion of
      cardiovascular disease. Our aims was to determine to what extent salts of
      potassium could substitute sodium chloride and potassium-rich soya flour could
      replace wheat flour without detrimental effect on acceptability, and to measure
      the bioavailability of a potassium salt added to bread. A single-blind
      organoleptic evaluation was carried out on eight different potassium-enriched
      breads by 41 panellists. Thereafter, six volunteers consumed standard or
      potassium-chloride-fortified bread in an 11-day single-blind cross-over feeding
      trial to determine the bioavailability of the supplemental potassium. Two breads
      in which 30% of the sodium was replaced by potassium salts, and bread in which
      10% of wheat flour was replaced with soy flour, had acceptability scores similar
      to the standard bread. In the metabolic study a supplement of 22 mmol/day
      potassium chloride incorporated into the bread was found to be wholly
      bioavailable. A substantial reduction in sodium and an increase in potassium
      intake could be achieved by substituting potassium salts for sodium chloride in
      bread.

PMID- 18608541
TI  - Content of essential polyunsaturated fatty acids in three canned fish species.
AB  - Three canned fish species--Pacific saury (Cololabis saira), Pacific herring
      (Clupea harengus) and Baltic sprat (Sprattus sprattus)--most common and popular
      in Russia, were analyzed for fatty acids. Special attention was paid to long
      chain essential polyunsaturated fatty acids: eicosapentaenoic acid (20:5omega3)
      and docosahexaenoic acid (22:6omega3). Sums of eicosapentaenoic acid and
      docosahexaenoic acid in saury, herring and sprat were, on average, 2.42, 1.80 and
      1.43 g/100 g product, respectively. Contents of these essential acids in all the
      canned fish species were found to be very high compared with many other fish
      reported in the available literature. All the canned fish appeared to be highly
      valuable products for human nutrition concerning the content of eicosapentaenoic
      and docosahexaenoic acids.

PMID- 18608543
TI  - Increasing consumption of breakfast cereal improves thiamine status in
      overweight/obese women following a hypocaloric diet.
AB  - The aim of this study was to analyse the thiamine status in a group of young,
      overweight/obese women and to analyse the changes in this status produced by two
      weight-control programmes based on approximating the diet to the theoretical
      ideal, increasing the relative consumption of vegetables (V) or cereals (C)
      (especially breakfast cereals). The study subjects were 57 Spanish women with a
      body mass index (BMI) of 24-35 kg/m(2), all of whom were randomly assigned to one
      of two slightly hypocaloric diets. Dietetic, anthropometric and biochemical data
      were collected at the beginning of the study and at 2 and 6 weeks. C and V
      subjects showed a reduction in their energy intake, body weight and BMI, both at
      2 and 6 weeks. Thiamine intake and blood thiamine levels only increased with diet
      C (both at 2 and 6 weeks). 21.8% cf the women, 21.8% had blood thiamine levels
      <150 nmol/L at the beginning of the study, but at 6 weeks of intervention only
      3.7% of the women in diet C, as compared with 30.8% of the women in diet V,
      showed blood thiamine levels <150 nmol/L. Although both diet C and diet V induced
      weight loss and a reduction in BMI, diet C would appear to be more useful in the
      maintenance of an adequate thiamine status.

PMID- 18608544
TI  - Amino acid composition determined using multiple hydrolysis times for three goat
      milk formulations.
AB  - The amino acid composition of goat milk formulations with varying protein and
      carbohydrate concentrations were determined. Proteins in goat milk infant
      formula, goat milk growing-up formula and goat whole milk powder were hydrolysed
      using multiple hydrolysis time intervals. A least-squares non-linear regression
      model was used to predict the free and protein bound amino acid concentrations.
      The amino acid composition of goat infant formula was compared with human milk
      reference values. There was good agreement between the multiple hydrolysis and
      single 24-h hydrolysis methods for approximately one-half of the amino acids.
      Tryptophan, aspartic acid, threonine, tyrosine, isoleucine, valine, serine and
      alanine contents were underestimated by 10.6, 5.6, 5.6, 4.7, 4.4, 3.7, 3.7 and
      3.6%, respectively, by the single 24-h hydrolysis. The study provides accurate
      reference data on the amino acid composition of goat milk powders. Goat milk
      infant formula has amino acids in amounts similar to human milk reference values,
      when expressed on a per-energy basis.

PMID- 18608545
TI  - Improved assay for determining the total radical-scavenging capacity of
      antioxidants and foods.
AB  - Free radicals play a crucial role in the pathophysiology of human diseases such
      as cancer, atherosclerosis, and neurodegenerative diseases, and considerable
      attention has been focused on functional foods (or nutraceuticals) that are able
      to decrease the concentrations of free radicals and consequently protect against
      these diseases. The present study investigated an improved quantitative assay to
      measure antioxidant activity using the stable and fast-reacting chromogenic
      indicator [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] (ABTS). The
      ABTS-radical-scavenging activities of various antioxidants and apple extracts
      were measured in 96-well plates, and plots thereof were linearly interpolated,
      with the total radical-scavenging capacity quantified as the area under the
      curve. The first order of linear regression was obtained in a relationship
      between the absorbance reduction and various concentrations of the tested sample,
      and the total radical-scavenging capacity was expressed as the vitamin-C
      equivalent antioxidant capacity. The advantages of this quantitative assay are
      that, first, it is fast, sensitive and confers little variation from experimental
      errors for single or mixed antioxidants; second, a large number of samples in a
      low quantity at a time can be run using 96-well plates.

PMID- 18608546
TI  - Antioxidant activity and polyphenol content of green tea flavan-3-ols and
      oligomeric proanthocyanidins.
AB  - The antioxidant activity and total phenolics content (TPC) of freshly prepared
      green tea extract (GTE) as affected by time, temperature and stirring were
      determined using the ferric reducing antioxidant power (FRAP) and Folin-Ciocalteu
      assays, respectively. Acetone-water fractions of GTE containing flavan-3-ols and
      oligomeric proanthocyanidins were evaluated at concentrations between 25 and 500
      ug/ml. Increasing the extraction time from 3 min to 10 min resulted in a
      significant increase in both the FRAP values and TPC. Increasing the extraction
      time from 10 min to 30 min was without any significant effects on both FRAP and
      TPC values. Moreover, the FRAP values were correlated with the TPC. GTE fractions
      had widely different FRAP values that were well correlated with the TPC of the
      fraction. It was concluded that brewing conditions such as extraction
      temperature, period of extraction, ratio of tea leaves to extracting water, and
      stirring are important factors for determining the FRAP values and TPC in GTE.
      These factors should be taken into consideration during preparation for
      nutritional benefits during usual consumption of this beverage. Elevated FRAP and
      TPC values corresponded to those GTE fractions with a higher amount of phenolic
      compounds, which have stronger antioxidant activities.

PMID- 18608547
TI  - Intake estimates of naturally occurring phytosterols using deterministic and
      probabilistic methods in a representative Irish population.
AB  - Intakes of naturally occurring phytosterols were estimated in the Irish
      population using phytosterol concentration data obtained from the published
      literature. Both deterministic and probabilistic approaches were used.
      Concentration data were applied to dietary intake data as assessed in the
      North/South Ireland Food Consumption Survey (n = 1,379). With the probabilistic
      approach, a uniform distribution was used in place of fixed values to reflect
      variability and uncertainty in phytosterol concentrations. Foods consumed were
      also categorized into 19 food groups, and the phytosterol intake per food group
      was calculated. Using the deterministic approach, mean phytosterol intake for the
      total population was 254 mg/day (28.1 mg/1,000 kJ). Using the probabilistic
      approach, slightly higher mean phytosterol intakes of 287 mg/day were found. In
      terms of food groups, 'bread and bread-rolls', 'vegetables and vegetable dishes'
      and 'spreading fat and oils' were the top three contributing food groups to
      phytosterol intakes. This study has shown how both deterministic and
      probabilistic approaches may be used to determine phytosterol intakes in a
      population.

PMID- 18608548
TI  - Effects of hydrogen peroxide treatment on thiol contents in fresh-cut asparagus
      (Asparagus officinalis) spears.
AB  - In this work, the impact of hydrogen peroxide (H2O2) was investigated on the
      thiol content of asparagus. Fresh-cut asparagus was treated with H2O2 at varied
      oxidant concentrations and contact times. A significant decrease (alpha=0.05) was
      observed in N-acetylcysteine levels treated with 2.5% H2O2 for 10 min and with 5%
      H2O2 for 3, 5 and 10 min. Captopril and cysteine levels significantly decreased
      (alpha=0.05) in all and most treatment conditions, respectively. Glutathione
      levels only significantly decreased with 2.5% and 5% H2O2 for 10 min treatment.
      In order to determine whether asparagus undergoes oxidative stress, a well-known
      oxidative stress indicator-the glutathione/oxidized glutathione ratio-was
      calculated. This study showed that the common use of H2O2 as a
      disinfectant/sterilizer by the food industry could markedly diminish the
      important biothiols and develop oxidative stress in asparagus, and potentially in
      other vegetables as well.

PMID- 18608549
TI  - Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in
      hyperlipidemic postmenopausal women.
AB  - BACKGROUND/AIM: Because of an unfavorable serum lipoprotein profile,
      postmenopausal women are at risk of cardiovascular disease. Soy protein may help
      protect against these risk factors, although its effect on paraoxonase 1 (PON1)
      is not clear. The aim of the present study was to determine the effects of soy
      protein on serum concentration of lipoproteins and PON1 activity in
      hypercholesterolemic postmenopausal women. DESIGN: In a double-blind randomized
      clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal
      women were randomly assigned to 50 g/day soy protein containing 164 mg
      isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were
      measured at baseline and at the 10th week. RESULTS: There was significant
      increase in PON1 activity (P=0.029) and a significant decrease in low-density
      lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density
      lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy
      group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and
      P=0.029, respectively) at the end of the study. Similarly, PON1 activity was
      significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL
      C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016
      and P=0.001) at the end of the study compared with the beginning value in soy
      group. CONCLUSION: Soy protein reduces the cardiovascular disease risk in
      postmenopausal women because of both modest reductions in serum lipoproteins and
      an increase in PON1 activity.

PMID- 18608550
TI  - Physical and chemical analysis of Passiflora seeds and seed oil from China.
AB  - The physical and chemical properties of seeds and seed oil from 'Tainung No. 1'
      passion fruit in China have been analyzed in order to evaluate their nutritional
      value. Proximate analysis shows that the seeds have a high amount of protein
      (10.8 +/- 0.60%) and are rich in oil (23.40 +/- 2.50%). The seeds are found to be
      a good source of minerals. They contain considerable amounts of sodium (2.980 +/-
      0.002 mg/g), magnesium (1.540 +/- 0.001 mg/g), potassium (0.850 +/- 0.001 mg/g),
      and calcium (0.540 +/- 0.002 mg/g). The passion fruit seeds contain the 17 amino
      acids that are found naturally in plant protein (tryptophan is not analyzed). The
      essential amino acids account for 34% of the 17 amino acids. The amino acid score
      of passion fruit seeds protein is 74 and the first limiting amino acid is
      methionine and cystine. The oil extracted by solvent and supercritical dioxide
      carbon is liquid at room temperature and the color is golden-orange. The specific
      gravity of the oil is about 0.917. Comparing the chemical properties of the oil
      extracted by solvent with that by supercritical dioxide carbon, the latter may be
      suitable as edible oil directly, while the former will be edible after it must be
      refined to improve on clarity. Fatty acid composition of the seed oil indicates
      that the oil contains two essential fatty acids (linoleic acid and linolenic
      acid), but the content of linoleic acid (72.69 +/- 0.32%) is by far greater than
      that of linolenic acid (0.26 +/- 0.00%). The present analytical results show the
      passion fruit seed to be a potentially valuable non-conventional source for high
      quality oil.

PMID- 18608551
TI  - Amino acid composition of the whole body, flesh and exoskeleton of female common
      West African fresh water crab Sudananautes africanus africanus.
AB  - The amino acid composition of the whole body (edible parts), flesh and
      exoskeleton of the female common West African fresh water crab Sudananautes
      africanus africanus was determined on a dry weight basis. The total essential
      amino acids ranged from 349.8 mg/g to 387.3 mg/g crude protein or from 48.5% to
      49.8% of the total amino acid. Both the total amino acid and the total essential
      amino acid showed no significant differences among the samples at P<0.05. The
      amino acid score showed that lysine ranged from 0.9 to 1.2, making it a good food
      fortifier. The predicted protein efficiency ratio was 2.6-3.4, showing that the
      quality of protein was high. The carbohydrate content was high (57.5-59.1 g/100
      g) but the protein was lower (15.7-18.6 g/100 g). The low level of the crude
      fibre in the flesh will make it good to serve as a food complement.

PMID- 18608552
TI  - Nutritional composition of three estuarine bivalve mussels, Perna viridis, Donax
      cuneatus and Meretrix meretrix.
AB  - The present study determined the nutrient composition of three bivalve mussels.
      The biochemical constituents (protein, carbohydrate, lipid and vitamins),
      minerals (iron, copper, zinc, calcium, magnesium, and manganese) and carbon,
      nitrogen and calorific values were evaluated. There was a high degree of
      variation in biochemical constituents and mineral components among the tested
      mussels. Perna viridis exhibited good nutritional composition when compared with
      Donax cuneatus and Meretrix meretrix. The results of this study showed that the
      samples possessed appreciable quantities of all the dietary elements tested,
      which could make them partial or complete substitutes for conventional seafood.

PMID- 18608553
TI  - Plasma amino acid response after ingestion of different whey protein fractions.
AB  - BACKGROUND AND OBJECTIVES: The digestion rate of proteins and subsequent
      absorption of amino acids can independently modulate protein metabolism. The
      objective of the present study was to examine the blood amino acid response to
      whey protein isolate (WPI), beta-lactoglobulin-enriched WPI, hydrolysed WPI and a
      flavour-identical control. METHODS: Eight healthy adults (four female, four male)
      were recruited (mean+/-standard error of the mean: age, 27.0+/-0.76 years; body
      mass index, 23.2+/-0.8 kg/cm(2)) and after an overnight fast consumed 500 ml of
      each drink, each containing 25g protein, in a cross-over design. Blood was taken
      at rest and then every 15 min for 2 h post ingestion. RESULTS: Ingesting the beta
      lactoglobulin-enriched WPI drink resulted in significantly greater plasma leucine
      concentrations at 45-120 min and significantly greater branched-chain amino acid
      concentrations at 60-105 min post ingestion compared with hydrolysed WPI. No
      differences were observed between WPI and beta-lactoglobulin-enriched WPI, and
      all protein drinks resulted in elevated blood amino acids compared with flavour
      identical control. CONCLUSIONS: In conclusion, whole proteins resulted in a more
      rapid absorption of leucine and branched-chain amino acid into the blood compared
      with the hydrolysed molecular form of whey protein.

PMID- 18608554
TI  - Tangerine tomatoes increase total and tetra-cis-lycopene isomer concentrations
      more than red tomatoes in healthy adult humans.
AB  - Lycopene, or the foods that contain it, may prevent prostate cancer. Studies
      suggest that some cis-lycopene isomers are more bioavailable than the trans
      lycopene isomer. We hypothesized that tangerine tomatoes, which predominantly
      contain the tetra-cis isomer, should be a good source of bioavailable lycopene.
      We fed lunches containing 300 g tangerine or red tomato sauce per day to 21
      healthy adults in a double-blind crossover design. We collected blood at baseline
      and after each treatment and washout period. We measured tetra-cis, other cis,
      and trans lycopene, as well as other carotenoids, by reversed-phase high
      performance liquid chromatography. Both tomato sauces increased lycopene
      concentrations in blood, but the tangerine tomato sauce caused a greater increase
      of total and tetra-cis-lycopene. The cis isomer(s) may also have facilitated
      absorption of the trans-lycopene isomer. Indices of oxidative damage decreased as
      serum lycopene concentrations increased. Our results suggest that total lycopene
      concentrations can be increased by substituting tetra-cis-lycopene-rich tangerine
      tomatoes for common red tomatoes in the diet.

PMID- 18608557
TI  - Nutritional composition, microbiological and sensory properties of dried melon: a
      traditional Turkmen product.
AB  - Seven different cultivars (Taze vaharman, Gokjek, Arap hatli, Turkmen vaharmani,
      Torli payendeke, Yazki bisek, Gizil gulabi) of honeydew melons (Cucumis melo L.)
      from Turkmenistan were processed to a dried traditional product known as 'kavun
      kaki' in order to evaluate the most suitable cultivar for drying process. The
      chemical composition (dry matter, crude oil, crude protein, crude fibre, energy,
      ash, water-soluble solids, total sugar, invert sugar, titratable acidity, pH and
      mineral contents) of the products was determined. The microbiological load (total
      aerobic bacteria, coliform bacteria and yeasts-moulds) of the samples were also
      evaluated. There were no significant differences between the odour, taste and
      texture scores of all the cultivars according to acceptance sensory analysis. The
      Turkmen Vaharmani and Torli payendeke samples had the highest colour scores.

PMID- 18608556
TI  - Influence of extrusion on the bioactive compounds and the antioxidant capacity of
      the bean/corn mixtures.
AB  - The aim of this investigation was to examine the influence of extrusion on the
      bioactive compounds and the antioxidant capacity of bean/corn mixtures. Whole
      bean flour and nixtamalized corn were mixed in a 60:40 proportion and extrusion
      was performed in different moisture (14.5%, 15.4%, 17.1% and 18.0%) and
      temperature (150 degrees C, 160 degrees C, 170 degrees C, 180 degrees C and 190
      degrees C) conditions in order to find the optimal extrusion conditions.
      According to their functional properties and antioxidant status, the mixtures 142
      degrees C/16.3% H, 170 degrees C/16.3% H and 198 degrees C/16.3% H were defined
      as optimal, moderate and bad, respectively. Total polyphenols and flavonoids in
      the mixture of 142 degrees C/16.3% H (15.09+/-1.7 mg gallic acid equivalent
      [GAE]/g dry weight [DW] and 1.57+/-0.2 mg catechin equivalent [CE]/g DW) were
      significantly higher (P<0.05) than in the sample 170 degrees C/16.3% H (9.42+/
      1.1 mg GAE/g DW and 1.4+/-0.1 mg CE/g DW) and the mixture 198 degrees C/16.3% H
      (6.46+/-0.8 mg GAE/g DW and 0.78+/-0.1 mg CE/g DW). The antioxidant activity
      (37.02+/-3.8 and 25.01+/-2.5 uM Trolox equivalent [TE]/g DW) of mixture 142
      degrees C/16.3% H, determined by the cupric reducing antioxidant capacity with
      Trolox equivalent antioxidant capacity and beta-carotene-linoleic acid (beta
      carotene,% of inhibition) assays, was significantly higher (P<0.05) than in 170
      degrees C/16.3% H (25.69+/-2.8 and 17.02+/-1.8 uM TE/g DW) and in mixture 198
      degrees C/16.3% H (13.93+/-1.5 and 8.94+/-0.9 uM TE/g DW), respectively. The free
      polyphenols, flavonoids and the antioxidant activities showed lower results than
      the hydrolyzed ones. The correlation coefficients between polyphenols,
      flavonoids, and cupric reducing antioxidant capacity capacities were between 0.93
      and 0.99.   In cereal proteins extracted and separated by electrophoresis, some
      differences were found in the sodium dodecyl sulfate-protein bands in the region
      from 36 to 45 kDa for 142 degrees C/16.3% H, in comparison with other samples.
      Therefore, there is a need to find such conditions for the extrusion procedures
      that would take into consideration the contents of the bioactive compounds and
      the antioxidant capacity in the end product.

PMID- 18608558
TI  - Effect of some essential oils on rheological properties of wheat flour dough.
AB  - The effects of summer savory (Satureja hortensis L.), majorana (Origanum vulgare
      L.), sage (Salvia triloba L), rosemary (Rosmarinus officinalis L.), pickling herb
      (Echinophora tenuifolia L.) and laurel (Laurus nobilis L.) essential oils on
      extensograph and farinograph characteristics of wheat flour doughs were
      determined. Also, some chemical properties (moisture content, ash content, wet
      gluten content, sedimentation value and falling number) were established. The
      results show that resistance to extension, maximum resistance, ratio number
      (minimum) and ratio number (maximum) values were increased by S. hortensis oil
      addition during the proving time. Extensibility values of S. hortensis, O.
      vulgare and S. triloba at 90 min of proving time were found lower that than those
      of other proving times (except S. triloba at 135 min). According to the
      extensograph results, rosemary, pickling herb and laurel oils allowed higher
      extensibility and energy, and lower resistance to extension and maximum
      resistance (Brabender Unit Line). The farinograph water absorption (500
      farinograph units) varied from 63.6 to 64.7. The development time of dough with
      rosemary oil was the same as the control group. Stabilities of dough with savory
      sater, majorana and sage oil were found lower that those of both control and
      other oils. As a result, rosemary, pickling herb and laurel oils had an advantage
      on the extensograph and farinograph characteristics of wheat flour dough.

PMID- 18608559
TI  - Impact of processing on the taurine content in processed seafood and their
      corresponding unprocessed raw materials.
AB  - Processing of foods can lead to losses of water-soluble components, and some of
      these may have beneficial health effects. Taurine has lately attracted attention
      due to its suggested strong contribution to the health-promoting effects of
      seafood. The lack of systematic information on the content of conditionally
      essential nutrients, such as taurine, has led to this study. The taurine
      concentrations in a variety of common marine dinners and spreads, and their
      corresponding raw materials, have been determined. Losses of taurine in processed
      products ranged up to 100% when compared with the taurine content of freshly
      caught specimens. Products soaked in brines or products subjected to rough
      processing conditions such as mincing and washing had greater loss compared with
      products with more intact muscle. Levels of taurine in processed seafood vary
      according to product type and brand, showing a potential for the industry to take
      measures in preventing losses of taurine and other water-soluble components.

PMID- 18608560
TI  - Pectin methylesterase activity and ascorbic acid  content from guava fruit, cv.
      Predilecta, in different  phases of development.
AB  - The guava pectin methylesterase (PME) specific activity and vitamin C were
      assayed in samples from different phases of guava fruit development. The PME
      enzyme from guava was extracted with borate-acetate buffer, 50 mol/l, pH 8.0, in
      the presence of NaCl 0.3 mol/l. The results showed PME optimum activity at pH 9
      and 95 degrees C, and it is a thermostable enzyme. Guava PME retained 96.8% of
      activity after 300 min in 90 degrees C. Electrophoresis showed that guava PME
      contained two isoforms, one with 57 kDa molecular mass. The analyses of the
      different phases of guava maturation showed that ascorbic acid decreases during
      the maturation process, but PME activity increases with maturation.

PMID- 18608561
TI  - Cross-sectional reference values for mid-upper arm circumference, triceps
      skinfold thickness and arm fat area of Turkish children and adolescents.
AB  - The aim of the study was to establish cross-sectional reference values for the
      mid-upper arm circumference (MUAC), triceps skinfold thickness (TSF) and arm fat
      area (AFA) of Turkish children and adolescents. In total 5,553 students aged
      between 6 and 17 years were selected by a multistage sampling method from schools
      representing city centre, rural and urban areas of Kayseri, Central Anatolia. The
      MUAC and TSF were measured, and the arm muscle area, arm area, AFA and fat
      percentage (%) were calculated. The LMS method was employed to calculate the
      MUAC, TSF and AFA curve parameters. The MUAC, TSF, AFA and fat percentage in each
      age group were significantly higher in girls than in boys. In boys, the TSF 50th
      percentile ranged from 7.6 mm at 17 years to 9.0 mm at 11 years; whereas in girls
      this ranged from 9.4 mm at 6 years to 14.6 mm at 17 years. The MUAC 50th
      percentile ranged from 17.0 to 23.6 cm in boys, and from 15.6 cm to 20.9 cm in
      girls. The AFA 50th percentile measurements ranged from 4.5 cm at 6 years to 5.8
      cm at 12-14 years in boys; and ranged from 7.2 cm at 6 years to 14.8 cm at 17
      years in girls. The percentile distribution was more disperse towards higher TSF
      and AFA values in boys than in girls.

PMID- 18608562
TI  - Digestive tolerance of inulin-type fructans: a double-blind, placebo-controlled,
      cross-over, dose-ranging, randomized study in healthy volunteers.
AB  - BACKGROUND: Similar to other indigestible carbohydrates or dietary fibres, a
      consumption of too large quantities of inulin-type fructans may cause some
      digestive problems. AIM: To compare the digestive tolerance of inulin-type
      fructans, administered during 2 weeks, at different doses. METHODS: Eighty-four
      healthy volunteers (aged 18-45 years, mean body mass index 25.1 kg/m2 and mean
      total fibre consumption 12 g) were included in a double-blind, placebo
      controlled, randomized, cross-over study comparing Fibrulose F97 (5 and 20
      g/day), Fibruline Instant (5, 10 and 20 g/day) and Fibruline XL (10 g/day)
      (degrees of polymerization respectively equal to 2-20, 2-60 with an average of
      10, and 2-60 with an average >20) to placebo. The study was decomposed into five
      2-week periods: placebo run-in, treatment 1, placebo washout, treatment 2,
      placebo run-out. The following symptoms were assessed using visual analogue
      scales: flatulence, rumbling, bloating, abdominal pain, abdominal cramps, nausea,
      stool frequency and stool consistency. The primary variable was the mean
      difference between treatment and placebo in terms of tolerance (sum of the eight
      visual analogue scales). RESULTS: The three products tended to increase digestive
      symptoms whatever the dose but the change was mild (maximum, +19 mm on the 800-mm
      scale) and significant (P<0.001) for Fibruline Instant at 20 g/day only. At 20
      g/day, a statistically significant difference between Fibruline Instant and
      Fibrulose F97 was demonstrated (P=0.011). There was a dose-effect relationship
      both for Fibrulose F97 (P>0.05) and Fibruline Instant (P=0.042). All the other
      tendencies were non-significant. CONCLUSIONS: The three different inulin-type
      fructans were very well tolerated.

PMID- 18608564
TI  - Degradation of total carotenoids and texture in frozen pumpkins when kept for
      storage under varying conditions of time and temperature.
AB  - The total carotenoid content and textural properties of pumpkin pieces thermally
      treated at 55 degrees C, 65 degrees C, 75 degrees C, 85 degrees C and 95 degrees
      C for different blanch times (3 min, 5 min, and 10 min) and subsequently kept for
      storage at 0 degrees C, -18 degrees C and -40 degrees C for a period of 80 days
      were measured. The total carotenoids content increased in the thermally treated
      pumpkin pieces, the increase being greater at 55 degrees C than at 95 degrees C.
      Storing the pumpkin pieces caused the total carotenoids content to decrease by 35
      40% at 0 degrees C, by 15-20% at -18 degrees C and by 25-30% at -40 degrees C. A
      low-temperature blanch gave a firmer texture to pumpkin in comparison with high
      temperature blanching. The texture of thermally treated pumpkins degraded when
      kept for storage, the losses being greater at 0 degrees C than at -18 degrees C
      and -40 degrees C. A split plot analysis was performed to study the effect of the
      factors on the retention of carotenoids.

PMID- 18608565
TI  - Is there any association between high-density lipoprotein, insulin resistance and
      non-alcoholic fatty liver disease in obese children?
AB  - Non-alcoholic fatty liver disease (NAFLD) is estimated to occur in about 50% of
      obese children. The purpose of this study is to examine the association of
      anthropometric, biochemical and liver indexes in obese children with and without
      NAFLD and its relation with insulin resistance (IR). Forty-three obese children
      participated in the study. NAFLD was diagnosed by ultrasonography. Liver indices
      (SGOT, SGPT), lipid profile, glucose and insulin levels were performed in all
      patients. IR was measured by means of the homeostasis model assessment and oral
      glucose insulin sensitivity. Among the 43 obese patients, 18/43 (41.8%) had NAFLD
      based on ultrasonography. Fifty percent of them had mild steatosis and 50% had
      moderate/severe steatosis. In logistic regression analysis of factors associated
      with NAFLD, homeostasis model assessment IR (ExpB, 1.607; 95% confidence
      interval, 1.058-2.440; P <0.02) and high-density lipoprotein (0.952; 95%
      confidence interval, 0.814-1.075; P <0.03) were the most significant. IR, as has
      already been proved, is associated with NAFLD. Furthermore, high-density
      lipoprotein levels seem to play an additional role in predicting NAFLD in obese
      children.

PMID- 18608567
TI  - In vitro uptake of beta-carotene by human exfoliated colonic epithelial cells.
AB  - The possible use of isolated exfoliated colonic epithelial cells in culture as an
      in vitro model to study the uptake of vitamin A and beta-carotene was tested.
      Freshly isolated exfoliated cells maintained in culture take up beta-carotene in
      a concentration-dependent manner. The uptake was found to increase in the
      presence of primary bile acids such as deoxy cholate, lipids such as triolein and
      lecithin in a concentration-dependent manner. These results suggest that
      exfoliated colonic epithelial cells isolated from stool samples of human subjects
      can be maintained in culture and serve as a useful non-invasive system to study
      the bioavailability of vitamin A and provitamin A carotenoids.

PMID- 18608568
TI  - Evaluation of trace elements released by edible clays in physicochemically
      simulated physiological media.
AB  - Physicochemical simulation (pH, electrolytes and temperature) of three
      physiological media was carried out in order to follow the release of trace
      elements contained in seven edible clays (mainly kaolinite, illite, muscovite and
      quartz) collected from the West African countries of Cote d'Ivoire, Guinee and
      Senegal. These clays are ingested by pregnant women for diverse reasons that are
      related to their condition. Simulated oral (6.5<pH<7), stomach (pH approximately
      1.8) and intestinal (pH approximately 8.3) media were prepared separately in
      order to compare the quantities of the trace elements released. Samples were
      analyzed by inductively coupled plasma emission spectrometry and
      spectrophotometry for the evaluation of copper, iron ((Fe(II) and Fe(III)), lead,
      manganese, nickel and zinc, since some of these elements can palliate deficiency
      problems and others can induce toxic effects. The quantities of the chemical
      elements released were pH dependent. The lower the pH, the higher the quantities
      of copper, Fe(III) and zinc. The quantities of Fe(II) were similar at both lower
      (stomach) and higher (intestinal) pH values. However, the quantities of
      manganese, nickel and lead were lower than quantification limits. Heating (110 
      degrees C) of the clays increased the quantities of trace elements released and
      could also participate in the microbiological 'decontamination' of raw materials.
      Microbiological analysis shows that all samples tested were in compliance with
      the recommendations of the European Pharmacopoeia. To verify the existence of
      possible beneficial and hazardous effects on human health, the quantities of
      copper, iron and zinc were compared with the recommended allowances for trace
      elements in France. In addition, the quantities of manganese, nickel and lead
      were compared with the maximum admissible concentrations in drinking water.

PMID- 18608569
TI  - Release of antioxidant components from tomatoes determined by an in vitro
      digestion method.
AB  - Tomatoes are an important source of antioxidant compounds, such as lycopene,
      phenolics and ascorbic acid. The main objective of this study was to determine
      the accessibility (availability for absorption) of the antioxidant compounds
      (total phenolics, total flavonoids, lycopene, ascorbic acid) and the antioxidant
      activity in fresh tomatoes of three cultivars (Excell, Tradiro and Flavourine)
      grown in New Zealand. The tomatoes were subjected to an in vitro digestion
      method, in which the pH, temperature, enzymes and chemical conditions were
      maintained according to human gastrointestinal conditions. The results showed
      that a high amount of the total phenolics and total flavonoids (71-77%) were
      released from tomatoes during digestion. However, only 3.2-4.5% of the total
      lycopene was released. No ascorbic acid could be detected after completion of in
      vitro digestion, probably due to degradation. After completion of digestion, the
      in vitro digestion extracts were found to have 45-50% antioxidant activity
      compared with the total antioxidant activity of fresh tomatoes (as measured by
      the 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid diammonium salt radical
      decolourization assay). This study shows that the antioxidant components of
      tomatoes were affected by the in vitro digestion conditions depending on the type
      of compound. This in vitro digestion method gives an estimate of the release of
      antioxidant components in tomato, which may predict their in vivo behaviour.

PMID- 18608571
TI  - The essential mineral concentration of Torba yoghurts and their wheys compared
      with yoghurt made with cows', ewes' and goats' milks.
AB  - Comparative studies on yoghurts made from cows', ewes' and goats' milks with
      respect to mineral concentrations are limited and warrant further investigation.
      The objective of this study was to analyse the gross chemical composition as well
      as the concentration of essential minerals in concentrated (torba) yoghurts made
      from cows', ewes' and goats' milk compared with those in regular yoghurts and
      wheys. The elements were determined by simultaneous inductively coupled plasma
      optical emission spectrometry. Ewe torba yoghurt was significantly higher in
      calcium, sodium, phosphorus, magnesium, selenium, zinc, cobalt, copper and iron
      concentrations compared with goat and cow torba yoghurts. It is recommended that
      torba yoghurts made from different types of milk may be considered an important
      source of phosphorus, calcium, magnesium, selenium and zinc over the regular
      yoghurts and wheys. Whey samples are also an excellent source of lactose as well
      as sodium and potassium.

PMID- 18608572
TI  - Global gene expression analyses reveal changes in biological processes after
      hyperthermia in a rat glioma model.
AB  - PURPOSE: To elucidate the thermal impact on biological processes the first three
      hours after hyperthermia (HT). MATERIALS AND METHODS: Tumor samples from BT(4)An
      rat tumors were transplanted subcutaneously to the right hind foot of BD IX rats,
      treated with local water-bath HT (mean tumor temperature of 43 degrees C) for one
      hour, and analyzed for changes in global gene expression the first three hours
      after treatment with HT. Samples from a corresponding in vitro experiment were
      also analyzed. Differentially expressed genes in vivo were mapped to a gene
      ontology (GO) database in search for biological processes overrepresented after
      treatment with HT. Selected genes were verified using Taqman quantitative RT-PCR.
      RESULTS: 1213 genes were differentially expressed after HT treatment in vivo.
      Processes overrepresented by GO mapping could be sorted into 10 main functional
      groups; apoptosis, transcription, immune system, blood vessels,
      metabolism/protein modifications, differentiation, cell signaling, response to
      stimulus, transport and cytoskeleton. We detected reduced mRNA levels of a wide
      range of T-cell, natural killer cell and antigen presenting cell-related genes
      after HT. CONCLUSION: To our best knowledge, this is the first global microarray
      analysis of a malignant tumor treated with HT in vivo. We highlight biological
      processes affected by HT. RNA expression profiles also indicate a rapid
      suppression of the immune system within tumors by local HT.

PMID- 18608573
TI  - Tumor microvascular permeability is a key determinant for antivascular  effects
      of doxorubicin encapsulated in a temperature sensitive   liposome.
AB  - Previous data have demonstrated that doxorubicin (DOX) released from a
      lysolecithin-containing thermosensitive liposome (LTSL) can shut down blood flow
      in a human tumor xenograft (FaDu) in mice when the treatment is combined with
      hyperthermia (HT), suggesting that LTSL-DOX is a potential antivascular agent. To
      further understand mechanisms of the treatment, we investigated effects of LTSL
      DOX (5 mg/kg body weight) plus HT (42 degrees C, 1 h) on microcirculation in
      another tumor (a murine mammary carcinoma, 4T07) implanted in mouse dorsal skin
      fold chambers and dose responses of tumor (FaDu and 4T07) and endothelial cells
      to LTSL-DOX or free DOX with or without HT. We observed that LTSL-DOXHT could
      significantly reduce blood flow and microvascular density in 4T07 tumors. The
      antivascular efficacy of LTSLDOX- HT could be enhanced through increasing tumor
      microvascular permeability of liposomes by using platelet activating factor
      (PAF). We also observed that the dose responses of FaDu and 4T07 to DOX in vitro
      were similar to each other and could be enhanced by HT. Taken together, these
      data suggested that tumor microvascular permeability was more critical than the
      sensitivity of tumor cells to DOX in determining the antivascular efficacy of
      LTSL-DOX-HT treatment.

PMID- 18608574
TI  - Augmentation of targeted delivery with pulsed high intensity focused ultrasound.
AB  - This paper reviews the enhanced delivery of genes, drugs and therapeutics using
      ultrasound. It begins with a general overview of the field and the various
      techniques associated with it, including sonophoresis, hyperthermia (with
      ultrasound), sonoporation, and microbubble assisted transvascular and targeted
      delivery. Particular attention is then paid to pulsed high intensity focused
      ultrasound drug delivery without the use of ultrasound contrast agents.
      Feasibility and mechanistic studies of this technique are described in some
      detail. Conclusions are then drawn regarding possible mechanisms of this
      treatment, and to contrast with the better known treatments relying on injection
      of ultrasound contrast agents.

PMID- 18608575
TI  - A polyacrylamide gel phantom for radiofrequency ablation.
AB  - A polyacrylamide gel (PAG) containing bovine serum albumin (BSA) is introduced as
      a new tissue-mimicking phantom for the purpose of visualizing three-dimensional
      coagulation temperature distribution during radiofrequency ablation (RFA). The
      coagulation temperature of the phantom can be changed at the same range of
      biological tissue (50-60 degrees C) by adjusting the pH from 4.3 to 4.7. The
      phantom is transparent except in thermal coagulation regions which are ivory
      white. The physical properties of the phantom, such as density, electrical
      conductivity and specific heat capacity, are very favorable, similar to those of
      soft tissues. We illustrate the usefulness of the phantom in visualizing RFA
      lesions. This phantom has magnetic resonance properties which change drastically
      upon thermal coagulation, enabling its use for the characterization of RFA
      device, quality assurance, treatment planning and treatment verification. The PAG
      containing BSA, whose pH was adjusted from 4.3 to 4.7, is an attractive tissue
      mimicking phantom suitable for RFA investigations.

PMID- 18608576
TI  - Heating applicator based on reentrant cavity with optimized local heating
      characteristics.
AB  - PURPOSE: A reentrant-cavity-based applicator can produce a concentrated electric
      field between reentrant electrodes for localized heating. However, this field is
      inadequate for treating early small tumors localized in the head and neck. In
      order to safely heat such well-localized lesions, the electric field distribution
      should be more localized. MATERIALS AND METHODS: In order to achieve localized
      heating, four parameters of the reentrant cavity (applicator height, outer
      diameter, reentrant diameter, and reentrant gap size), which influence the
      distribution of the electric field produced in the reentrant gap, are optimized
      using the Taguchi method. The variation in the heating characteristics affected
      by the size of the heating object is estimated using the signal-to-noise ratio
      (SNR) index. In this study, the electromagnetic field distributions in a
      cylindrical phantom and an oblate sphere phantom are analyzed by the three
      dimensional finite element method, and the full width at half height (FWHH) of
      the specific absorption rate (SAR) distribution in the reentrant gap is
      evaluated. RESULTS: It is shown that the optimized applicator yields both the
      maximum SNR and minimum mean FWHH, and the sizes of the heating region in the
      phantom expressed using the averaged FWHH values of the SAR distribution are 60
      and 80 mm along the radial and long-axis directions of the applicator,
      respectively. CONCLUSIONS: A heating region can be robustly and optimally
      localized by using the Taguchi method and considering the variation in the size
      of the heating object.

PMID- 18608577
TI  - Genes and genetic networks responsive to mild hyperthermia in human lymphoma U937
      cells.
AB  - In this study, to better understand the molecular mechanism underlying cellular
      responses to mild hyperthermia, we investigated gene expression patterns and
      genetic networks in human myelomonocytic lymphoma U937 cells using high-density
      oligonucleotide microarrays and computational gene expression analysis tools. The
      cells were incubated at 41 degrees C for 30 min (mild hyperthermia treatment) and
      then at 37 degrees C for 0-6 h. Although the mild hyperthermia treatment of the
      cells did not induce apoptosis, significant increases in the protein expression
      levels of heat shock proteins (HSPs), namely, Hsp27, Hsp40 and Hsp70, were
      observed following the activation of heat shock factor-1. Of the 22,283 probe
      sets analyzed, 423 probe sets were up-regulated and 515 probe sets were down
      regulated by >1.5-fold in the cells 3 h post-treatment. Computational gene
      network analysis demonstrated that the significant genetic network A that
      contained many HSPs such as DNAJB1, HSPA1A, and HSPA1B was associated with
      cellular function and maintenance, post-transcriptional modification, or protein
      folding. Moreover, the significant genetic network B whose core contained v-myc
      myelocytomatosis viral oncogene homolog (MYC) was associated with cell
      morphology, cell cycle, and cellular development. The expression levels of nine
      selected genes were comparable to those determined by microarray analysis with
      real-time quantitative PCR assay. The present results indicate that mild
      hyperthermia affects the expression of a large number of genes and provides
      additional novel insights into the molecular basis of mild hyperthermia in cells.

PMID- 18608579
TI  - p53 status-dependent sensitization of human tumour cells to hyperthermia by plant
      flavonol.
AB  - PURPOSE: Quercetin (QCT), an important flavonol, is known to sensitize tumour
      cells to hyperthermia by suppressing heat shock protein 72 (Hsp72) induction, and
      is also reported to inhibit p53 accumulation. This study was conducted to examine
      the effects of QCT on the heat sensitivities of human tumour cell lines with
      different p53 statuses. MATERIAL AND METHODS: Cell lines derived from human
      cancers and p53-inducible cells were used. After heat treatment at 43 degrees C
      for 2 h with or without QCT, cell survival was determined in a clonogenic assay.
      The cellular and nuclear content of Hsp72 as well as that of p53 was determined
      by Western blotting analysis. RESULTS: Treatment of cells with 150 microM QCT,
      which completely abolished Hsp72 induction, potentiated the lethal effects of
      hyperthermia in all tumour cell lines. Particularly, remarkable enhancement of
      cell death was observed in tumour cell lines having little or no p53 proteins.
      Although nuclear translocation of Hsp72 is induced by hyperthermia, it was
      significantly compromised in p53-deficient cells. CONCLUSIONS: These results
      indicate that p53 is a component for nuclear accumulation of Hsp72; therefore,
      p53 status is an important determinant of the sensitization of human tumour cells
      to hyperthermia by QCT.

PMID- 18608578
TI  - In vitro and in vivo evaluations of increased effective beam width for heat
      deposition using a split focus high intensity ultrasound (HIFU) transducer.
AB  - PURPOSE: To develop a novel and efficient, in vitro method for characterizing
      temporal and spatial heat generation of focused ultrasound exposures, and
      evaluate this method to compare a split focus and conventional single focus high
      intensity focused ultrasound transducer. MATERIALS AND METHODS: A HIFU tissue
      mimicking phantom was validated by comparing respective temperature elevations
      generated in the phantoms and in murine tumors in vivo. The phantom was then used
      in combination with IR thermography to spatially and temporally characterize
      differences in low-level temperature elevation (e.g. 3-5 degrees C) produced by a
      single focus and split focus HIFU transducer, where the latter produces four
      simultaneous foci. In vivo experiments with heat sensitive liposomes containing
      doxorubicin were then carried out to determine if the larger beam width of the
      split focus transducer, compared to the single focus, could increase overall
      deployment of the drug from the liposome. RESULTS: Temperature elevations
      generated in the HIFU phantom were not found to be different from those measured
      in vivo when compensating for disparities in attenuation coefficient and specific
      heat, and between the two transducers by increasing the energy deposition.
      Exposures with the split focus transducer provided significant increases in the
      area treated compared to the single focus, which then translated to significant
      increases in drug deposition in vivo. CONCLUSIONS: Preliminary evidence was
      provided indicating the potential for using this novel technique for
      characterizing hyperthermia produced by focused ultrasound devices. Further
      development will be required for its suitability for correlating in vitro and in
      vivo outcomes.

PMID- 18608580
TI  - Computer modeling of the combined effects of perfusion, electrical conductivity,
      and thermal conductivity on tissue heating patterns in radiofrequency tumor
      ablation.
AB  - PURPOSE: To use an established computer simulation model of radiofrequency (RF)
      ablation to characterize the combined effects of varying perfusion, and
      electrical and thermal conductivity on RF heating. METHODS: Two-compartment
      computer simulation of RF heating using 2-D and 3-D finite element analysis
      (ETherm) was performed in three phases (n = 88 matrices, 144 data points each).
      In each phase, RF application was systematically modeled on a clinically relevant
      template of application parameters (i.e., varying tumor and surrounding tissue
      perfusion: 0-5 kg/m(3)-s) for internally cooled 3 cm single and 2.5 cm cluster
      electrodes for tumor diameters ranging from 2-5 cm, and RF application times (6
      20 min). In the first phase, outer thermal conductivity was changed to reflect
      three common clinical scenarios: soft tissue, fat, and ascites (0.5, 0.23, and
      0.7 W/m- degrees C, respectively). In the second phase, electrical conductivity
      was changed to reflect different tumor electrical conductivities (0.5 and 4.0
      S/m, representing soft tissue and adjuvant saline injection, respectively) and
      background electrical conductivity representing soft tissue, lung, and kidney
      (0.5, 0.1, and 3.3 S/m, respectively). In the third phase, the best and worst
      combinations of electrical and thermal conductivity characteristics were modeled
      in combination. Tissue heating patterns and the time required to heat the entire
      tumor +/-a 5 mm margin to >50 degrees C were assessed. RESULTS: Increasing
      background tissue thermal conductivity increases the time required to achieve a
      50 degrees C isotherm for all tumor sizes and electrode types, but enabled
      ablation of a given tumor size at higher tissue perfusions. An inner thermal
      conductivity equivalent to soft tissue (0.5 W/m- degrees C) surrounded by fat
      (0.23 W/m- degrees C) permitted the greatest degree of tumor heating in the
      shortest time, while soft tissue surrounded by ascites (0.7 W/m- degrees C) took
      longer to achieve the 50 degrees C isotherm, and complete ablation could not be
      achieved at higher inner/outer perfusions (>4 kg/m(3)-s). For varied electrical
      conductivities in the setting of varied perfusion, greatest RF heating occurred
      for inner electrical conductivities simulating injection of saline around the
      electrode with an outer electrical conductivity of soft tissue, and the least
      amount of heating occurring while simulating renal cell carcinoma in normal
      kidney. Characterization of these scenarios demonstrated the role of electrical
      and thermal conductivity interactions, with the greatest differences in effect
      seen in the 3-4 cm tumor range, as almost all 2 cm tumors and almost no 5 cm
      tumors could be treated. CONCLUSION: Optimal combinations of thermal and
      electrical conductivity can partially negate the effect of perfusion. For
      clinically relevant tumor sizes, thermal and electrical conductivity impact which
      tumors can be successfully ablated even in the setting of almost non-existent
      perfusion.

PMID- 18608582
TI  - Differential capacity of chaperone-rich lysates in cross-presenting human
      endogenous and exogenous melanoma differentiation antigens.
AB  - The goal of immune-based tumor therapies is the activation of immune cells
      reactive against a broad spectrum of tumor-expressed antigens. Vaccines based on
      chaperone proteins appear promising as these proteins naturally exist as
      complexes with various protein fragments including those derived from tumor
      associated antigens. Multi-chaperone systems are expected to have highest
      polyvalency as different chaperones can carry distinct sets of antigenic
      fragments. A free-solution isoelectric focusing (FS-IEF) technique was
      established to generate chaperone-rich cell lysates (CRCL). Results from murine
      systems support the contention that CRCL induce superior anti-tumor responses
      than single chaperone vaccines. We established an in vitro model for human
      melanoma to evaluate the capacity of CRCL to transfer endogenously expressed
      tumor antigens to the cross-presentation pathway of dendritic cells (DC) for
      antigen-specific T cell stimulation. CRCL prepared from human melanoma lines
      contained the four major chaperone proteins Hsp/Hsc70, Hsp90, Grp94/gp96 and
      calreticulin. The chaperones within the melanoma cell-derived CRCL were
      functionally active in that they enhanced cross-presentation of exogenous
      peptides mixed into the CRCL preparation. Superior activity was observed for
      Hsp70-rich CRCL obtained from heat-stressed melanoma cells. Despite the presence
      of active chaperones, melanoma cell-derived CRCL failed to transfer endogenously
      expressed melanoma-associated antigens to DC for cross-presentation and cytotoxic
      T cell (CTL) recognition, even after increasing intracellular protein levels of
      tumor antigen or chaperones. These findings reveal limitations of the CRCL
      approach regarding cross-presentation of endogenously expressed melanoma
      associated antigens. Yet, CRCL may be utilized as vehicles to enhance the
      delivery of exogenous antigens for DC-mediated cross-presentation and T cell
      stimulation.

PMID- 18608583
TI  - Challenges in the development of magnetic particles for therapeutic applications.
AB  - Certain iron-based particle formulations have useful magnetic properties that,
      when combined with low toxicity and desirable pharmacokinetics, encourage their
      development for therapeutic applications. This mini-review begins with background
      information on magnetic particle use as MRI contrast agents and the influence of
      material size on pharmacokinetics and tissue penetration. Therapeutic
      investigations, including (1) the loading of bioactive materials, (2) the use of
      stationary, high-gradient (HG) magnetic fields to concentrate magnetic particles
      in tissues or to separate material bound to the particles from the body, and (3)
      the application of high power alternating magnetic fields (AMF) to generate heat
      in magnetic particles for hyperthermic therapeutic applications are then
      surveyed. Attention is directed mainly to cancer treatment, as selective
      distribution to tumors is well-suited to particulate approaches and has been a
      focus of most development efforts. While magnetic particles have been explored
      for several decades, their use in therapeutic products remains minimal; a
      discussion of future directions and potential ways to better leverage magnetic
      properties and to integrate their use into therapeutic regimens is discussed.

PMID- 18608584
TI  - RF ablation with adjuvant therapy: comparison of external beam radiation and
      liposomal doxorubicin on ablation efficacy in an animal tumor model.
AB  - PURPOSE: To determine the critical thermal dosimetry and relative efficacy for RF
      ablation combined with external beam radiation (XRT) or liposomal doxorubicin
      (LD), in an animal tumor model. MATERIALS AND METHODS: This study was performed
      in two phases, in 13-18 mm diameter R3230 tumors subcutaneously implanted into
      Fischer rats. In phase 1, tumors (n = 30) were randomized into six groups. RF
      energy (titrated to 70 degrees C tip temperature) was applied for either 2.5 or 5
      min (n = 15, each group). For each duration, one of three adjuvant therapies was
      applied (n = 5, each): no therapy (control), LD (1 mg intravenously, 30 min post
      RF), or XRT (20 Gy at 1 Gy min(-1), within 2 h post-RF), with sacrifice at 48 h
      for pathologic analysis. In phase 2, thermal mapping was performed in 20 tumors
      throughout RF application (70 degrees C; 5 min), at 1.5-7 mm distances from the
      active electrode tip. Temperature profiles throughout the tumor were constructed
      and were used to interpolate temperatures over time at the critical ablation
      margin, to derive maximum threshold temperature, AUC (area under the curve) and
      CEM(43) (cumulative equivalent minutes at 43 degrees C). Ablation sizes and all
      calculated values were compared within and across experimental groups using
      MANOVA statistics with pair-wise T-test for individual comparisons. RESULTS:
      RF/XRT produced the largest coagulation (11.7 +/- 1.5 mm at 2.5 min, >or=15 +/-
      0.7 mm at 5 min), followed by RF/LD, and then RF alone (p < 0.001 for all
      comparisons). RF/XRT demonstrated temperature threshold decreases from RF alone
      of 11.7 +/- 0.01 degrees C and 12.7 +/- 0.38 degrees C at 2.5 and 5 min
      respectively (with absolute thresholds of 42 degrees C for XRT compared to 52
      degrees C for RF alone). RF/LD had decreases of 4.0 degrees C at 2.5 min and 4.4
      degrees C at 5 min. Thermal dose requirements (AUC) decreased by 7.79% or 9.28%
      for RF/LD compared to >or=19.36% or 25.82% for RF/XRT at 2.5 and 5 min (p <
      0.001). CEM(43) values followed similar patterns (p < 0.001), but with a
      reduction of 10(1) and 10(4) in magnitude for RF/LD and RF/XRT therapies at 5
      min, respectively. CONCLUSIONS: For a standardized RF dose, the combination of
      high dose XRT and RF increased ablation size compared to RF and liposomal
      doxorubicin or RF alone. Increased ablation size is more closely associated with
      decreased temperature threshold necessary to induce coagulation, rather than the
      total thermal dose.

PMID- 18608585
TI  - Anti-tumor effect of sodium-induced thermochemical ablation therapy.
AB  - PURPOSE: We have recently proposed utilizing alkali metal as powerful self
      heating seeds to thermally ablate tumor tissues. This study is dedicated to
      disclosing some fundamental mechanisms related to the anti-tumor effects of
      sodium and its controllability as an economic, safe and efficient thermochemical
      agent in targeted tumor treatment. MATERIALS AND METHODS: EMT6 cell line was
      incubated under four situations: no treatment, NaOH solution treatment,
      hyperthermia treatment and a combined NaOH solution and hyperthermia treatment.
      Cell cytotoxicity was measured by a CASY cell counter and analyzer system. Breast
      EMT6 tumors in mice were subjected to treatment by NaOH solution, hyperthermia
      and encapsulated sodium. The changes of tumor volumes were continuously measured
      for 12 days after treatment. Tumors of another four mice were harvested
      immediately after treatment to assess viability. RESULTS: In vitro cell
      experiments suggested that thermal effect combined with chemical treatment
      produced a more significant cell cytotoxicity compared to thermal or chemical
      treatment alone. Encapsulated sodium demonstrated a slower and more continuous
      heat release than bare sodium. The sodium treatment produced a dramatic
      regression of tumors that lasted throughout the 12 days of the study.
      Histological sections showed complete necrosis in sodium-treated tumors, whereas
      control tumors and heat-treated tumors remained viable, and NaOH-treated tumors
      showed partial destruction. CONCLUSIONS: The results suggest that sodium allows a
      minimally invasive treatment which could produce both thermal and chemical lethal
      injury to tumors. Using sodium to ablate target tumors is potentially an
      effective, safe and low cost way to treat malignant tumors.

PMID- 18608586
TI  - Radiofrequency ablation: the effect of distance and baseline temperature on
      thermal dose required for coagulation.
AB  - PURPOSE: To determine the effects of applied current, distance from an RF
      electrode and baseline tissue temperature upon thermal dosimetry requirements to
      induce coagulation in ex vivo bovine liver and in vivo porcine muscle models.
      MATERIALS AND METHODS: RF ablation was performed in ex vivo liver at varying
      baseline temperatures-19-21 degrees C (n = 114), 8-10 degrees C (n = 27), and 27
      28 degrees C (n = 27)-using a 3-cm tip electrode and systematically varied
      current 400-1,300 mA, to achieve defined diameters of coagulation (20, 30 and 40
      +/- 2 mm), and in in vivo muscle (n = 18) to achieve 35 mm +/- 2 mm of
      coagulation. Thermal dose required for coagulation was calculated as the area
      under the curve and cumulative equivalent minutes at 43 degrees C. RESULTS:
      Thermal dose correlated with current in a negative exponential fashion for all
      three diameters of coagulation in ex vivo experiments (p < 0.001). The
      temperatures at the end of RF heating at the ablation margin were not
      reproducible, but varied 38 degrees C-74.7 degrees C, for 30 mm coagulation in ex
      vivo liver, and 59.8 degrees C-68.4 degrees C in the in vivo experiment. CEM(43)
      correlated with current as a family of positive exponential functions (r(2) =
      0.76). However, a very wide range of CEM(43) values (on the order of 10(15)) was
      noted. Although baseline temperatures in the ex vivo experiment did not change
      required thermal dose, the relationships between end temperature at the ablation
      margin and RF current were statistically different (p < 0.001) as analysed at the
      400 mA intercept. CONCLUSIONS: In both models, thermal dosimetry required to
      achieve coagulation was not constant, but current and distance dependent. Hence,
      other formulas for thermal dose equivalence may be needed to predict conditions
      for thermal ablation.

PMID- 18608587
TI  - Long-term functional outcome after hyperthermic isolated limb perfusion (HILP).
AB  - BACKGROUND: One of the biological characteristics of melanoma is the locoregional
      development of metastases that are difficult to treat by conventional tumour mass
      reduction. Locoregionally metastasised melanoma of the limb can effectively be
      treated by hyperthermic isolated limb perfusion (HILP). Postoperative
      complication rates are acceptable. Only few studies have examined long-term
      complications. This is the reason why we followed up patients in respect of long
      term physical and psychological complications after HILP. MATERIALS AND METHODS:
      312 patients with melanoma of the limb underwent HILP in our department between
      1977 and 1983. Eighty-two patients that were still alive and no older than 80
      years at the time of follow-up were contacted and invited to a physical
      examination. On average, follow-up took place 20 years after HILP. Thirty-nine
      patients were willing to participate in the study. Twelve of these patients were
      male and 27 female. The average age was 63.1 years (range 41 to 79). The average
      age at the point of perfusion was 42.1 years (range 19 to 59). In 10 cases the
      upper extremity was involved, in 29 patients the lower extremity. Patients were
      questioned on impairment of daily life and their health status using a
      standardised questionnaire. A physical examination was performed to document the
      impairments quantitatively. Ranges of motion, circumference and neurological
      deficits of the operated limbs were compared to the healthy limbs. RESULTS: At
      the time of follow-up examination all patients were without recurrent disease. A
      definite correlation between impairment of the general health condition and the
      operation could only be found in one patient with persisting lymph oedema.
      Thirteen patients still wore elastic stockings during the day, 9 of which
      regularly underwent lymphatic drainage. Most of the patients (58%) saw an
      improvement of their condition due to the treatment. 67% of the patients reported
      not having any or only slight impairment of everyday life. Only a few cases had
      disadvantages in their social and working life due to the perfusion. The physical
      examination of the upper limb showed an impaired range of motion of the shoulder
      in all planes in 50% of the patients. Relevant decrease in range of motion in the
      elbow was seen in two patients. The other examination results showed no
      significant differences in comparison to the healthy arm. The analysis of the
      lower limb showed relevant clinical reduction of range of motion in all three
      major joints. Significant differences were also found in the circumference of the
      leg compared to the healthy side. SUMMARY: According to our results and results
      from the literature it was possible to show that hyperthermic isolated limb
      perfusion is associated with an elevated risk of persisting impairment of range
      of motion of the treated limb. The impaired function is due to a persistent
      swelling of the limb because of lymph oedema on the one hand and local toxicity
      to the ligaments of the joints on the other. Response rates and results of HILP
      have greatly improved in the last years due to numerous modifications so that
      this treatment is the method of choice in locoregionally metastasised melanoma of
      the limb in spite of the long-term complication rate.

PMID- 18608588
TI  - Microwave thermal imaging of scanned focused ultrasound heating: phantom results.
AB  - We are developing a microwave tomographic imaging system capable of monitoring
      thermal distributions based on the temperature dependence of the recovered
      dielectric properties. The system has been coupled to a high intensity focused
      ultrasound (HIFU) therapy device which can be mechanically steered under computer
      control to generate arbitrarily shaped heating zones. Their integration takes
      advantage of the focusing capability of ultrasound for the therapy delivery and
      the isolation of the microwave imaging signal from the power deposition source to
      allow simultaneous treatment monitoring. We present several sets of phantom
      experiments involving different types of heating patterns that demonstrate the
      quality of both the spatial and temporal thermal imaging performance. This
      combined approach is adaptable to multiple anatomical sites and may have the
      potential to be developed into a viable alternative to current clinical
      temperature monitoring devices for HIFU, such magnetic resonance (MR) imaging.

PMID- 18608589
TI  - In vivo change in ultrasonic backscattered energy with temperature in motion
      compensated images.
AB  - Ultrasound is an attractive modality for non-invasive imaging to monitor
      temperature of tumorous regions undergoing hyperthermia therapy. Previously, we
      predicted monotonic changes in backscattered energy (CBE) of ultrasound with
      temperature for certain sub-wavelength scatterers. We also measured CBE values
      similar to our predictions in bovine liver, turkey breast muscle, and pork rib
      muscle in both 1D and 2D in in vitro studies. To corroborate those results in
      perfused, living tissue, we measured CBE in both normal tissue and in implanted
      human tumors (HT29 colon cancer line) in 7 nude mice. Images were formed by a
      phased-array imager with a 7.5 MHz linear probe during homogeneous heating from
      37 degrees to 45 degrees C in 0.5 degrees C steps and from body temperature to 43
      degrees C during heterogeneous heating. We used cross-correlation as a similarity
      measure in RF signals to automatically track feature displacement as a function
      of temperature. Feature displacement was non-uniform with a maximum value of 1 mm
      across all specimens during homogeneous heating, and 0.2 mm during heterogeneous
      heating. Envelopes of image regions, compensated for non-rigid motion, were found
      with the Hilbert transform then smoothed with a 3 x 3 running average filter
      before forming the backscattered energy at each pixel. Means of both the positive
      and negative changes in the BE images were evaluated. CBE was monotonic and
      accumulated to 4-5 dB during homogeneous heating to 45 degrees C and 3-4 dB
      during heterogenous heating to 43 degrees C. These results are consistent with
      our previous in vitro measurements and support the use of CBE for temperature
      estimation in vivo during hyperthermia.

PMID- 18608590
TI  - Temperature sensitive peptides: engineering hyperthermia-directed therapeutics.
AB  - PURPOSE: Recent progress suggests that short peptide motifs can be engineered
      into biopolymers with specific temperature dependent behavior. This review
      discusses peptide motifs capable of thermo-responsive behavior, and broadly
      summarizes design approaches that exploit these peptides as drug carriers. This
      review focuses on one class of thermally responsive peptide-based biopolymers,
      elastin-like polypeptides in greater detail. ANALYSIS: Four peptide motifs are
      presented based on leucine zippers, human collagen, human elastin, and silkworm
      silk that are potential building blocks for thermally responsive biopolymers.
      When these short motifs (<7 amino acids) are repeated many times, they generate
      biopolymers with higher order structure and complex temperature triggered
      behaviors. These structures are thermodynamically modulated, making them
      intrinsically temperature sensitive. These four motifs can be categorized by the
      directionality and reversibility of association. Elastin-like polypeptides (ELPs)
      are one promising motif that reversibly associates during heating. ELPs aggregate
      sharply above an inverse phase transition temperature, which depends on polymer
      hydrophobicity, molecular weight, and concentration. ELPs can be modified with
      chemotherapeutics, are biodegradable, are biocompatible, have low immunogenicity,
      and have terminal pharmacokinetic half-lives >8 h. ELP block copolymers can
      reversibly form micelles in response to hyperthermia, and this behavior can
      modulate the binding avidity of peptide ligands. When high molecular weight ELPs
      are systemically administered to mice they accumulate in tumors; furthermore,
      hyperthermia can initiate the ELP phase transition and double the concentration
      of peptide in the tumor. CONCLUSIONS: Temperature sensitive peptides are a
      powerful engineering platform that will enable new strategies for hyperthermia
      directed drug delivery.

PMID- 18608591
TI  - Regional hyperthermia of the abdomen in conjunction with chemotherapy for
      peritoneal carcinomatosis: evaluation of two annular-phased-array applicators.
AB  - BACKGROUND: Peritoneal carcinomatosis is a stage of gynecological and
      gastrointestinal malignancies with poor prognosis. Options for enhancing the
      effect of standard chemotherapy, such as aggressive surgery and intraperitoneal
      chemotherapy, have limitations. In this phase I/II study, we evaluated regional
      hyperthermia of the pelvis and abdomen using the annular-phased-array technique
      as an adjunct to chemotherapy. METHODS: Forty-five patients with peritoneal
      carcinomatosis (with or without liver metastases) in colorectal cancer (CRC) (n =
      16), ovarian cancer (OC) (n = 17), or gastric/pancreatic/biliary cancer (n = 12)
      underwent standard chemotherapy and regional hyperthermia. Most CRC patients
      received second-line chemotherapy. All OC patients were platinum resistant.
      Regional hyperthermia was applied using a SIGMA-60 applicator (OC), a SIGMA
      Eye/MR applicator (CRC), or various ring applicators (gastric/pancreatic/biliary
      cancer). RESULTS: Abdominal regional hyperthermia was well tolerated, with
      acceptable acute discomfort and no long-term morbidity. The SIGMA-Eye/MR
      applicator achieved higher systemic temperatures (associated with higher systemic
      stress) and more effective heating of the upper abdomen; the SIGMA-60 applicator
      achieved higher temperatures (and power densities) in the pelvis. Three-year
      overall survival was encouraging for patients with CRC (22%) and OC (29%) but not
      gastric/pancreatic/biliary cancer. For the SIGMA-60 applicator (patients with
      OC), higher measured temperatures at the vaginal stump correlated with better
      outcome. CONCLUSIONS. The SIGMA-60 and SIGMA-Eye/MR applicators are feasible for
      abdominal heating and have low toxicity. The SIGMA-60 applicator is specifically
      suitable for malignancies with high pelvic burden; the SIGMA-Eye/MR applicator
      better heats the upper abdomen, including the liver. Further randomized
      investigations are warranted.

PMID- 18608592
TI  - Feasibility of concurrent treatment with the scanning ultrasound reflector linear
      array system (SURLAS) and the helical tomotherapy system.
AB  - PURPOSE: To evaluate the feasibility of concurrent treatment with the scanning
      ultrasound reflector linear array system (SURLAS) and helical tomotherapy (HT)
      intensity modulated radiation therapy (IMRT). METHODS: The SURLAS was placed on a
      RANDO phantom simulating a patient with superficial or deep recurrent breast
      cancer. A megavoltage CT (MVCT) of the phantom with and without the SURLAS was
      obtained in the HT system. MVCT images with the SURLAS were obtained for two
      configurations: (1) with the SURLAS's long axis parallel and (2) perpendicular to
      the longitudinal axis of the phantom. The MVCT simulation data set was then
      transferred to a radiation therapy planning station. Organs at risk (OAR) were
      contoured including the lungs, heart, abdomen and spinal cord. The metallic parts
      of the SURLAS were contoured as well and constraints were assigned to completely
      or directionally block radiation through them. The MVCT simulation data set and
      regions of interest (ROI) files were subsequently transferred to the HT planning
      station. Several HT plans were obtained with optimization parameters that are
      usually used in the clinic. For comparison purposes, planning was also performed
      without the SURLAS on the phantom. RESULTS: All plans with the SURLAS on the
      phantom showed adequate dose covering 95% of the planning target volume (PTV
      D95%), average dose and coefficient of variation of the planning target volume
      (PTV) dose distribution regardless of the SURLAS's orientation with respect to
      the RANDO phantom. Likewise, all OAR showed clinically acceptable dose values.
      Spatial dose distributions and dose-volume histogram (DVH) evaluation showed
      negligible plan degradation due to the presence of the SURLAS. Beam-on time
      varied depending on the selected optimization parameters. CONCLUSION: From the
      perspective of the radiation dosage, concurrent treatment with the SURLAS and HT
      IMRT is feasible as demonstrated by the obtained clinically acceptable treatment
      plans. In addition, proper orientation of the SURLAS may be of benefit in
      reducing dose to organs at risk in some cases.

PMID- 18608593
TI  - Clinical applications of magnetic nanoparticles for hyperthermia.
AB  - Magnetic fluids are increasingly used for clinical applications such as drug
      delivery, magnetic resonance imaging and magnetic fluid hyperthermia. The latter
      technique that has been developed as a cancer treatment for several decades
      comprises the injection of magnetic nanoparticles into tumors and their
      subsequent heating in an alternating magnetic field. Depending on the applied
      temperature and the duration of heating this treatment either results in direct
      tumor cell killing or makes the cells more susceptible to concomitant radio- or
      chemotherapy. Numerous groups are working in this field worldwide, but only one
      approach has been tested in clinical trials so far. Here, we summarize the
      clinical data gained in these studies on magnetic fluid induced hyperthermia.

PMID- 18608594
TI  - Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and
      daily interferon-alpha: a description of a phase I-II protocol.
AB  - PURPOSE: The purpose of the Phase I component of this study was to find the
      maximally tolerated dose (MTD) of cisplatin administered within a regimen of
      fever-range whole body thermal therapy (FR-WB-TT), cisplatin, gemcitabine, and
      low-dose interferon-alpha (IFN-alpha). The Phase II component aimed to assess
      which cancer diagnoses responded to the regimen, the response rate, and response
      duration. MATERIALS AND METHODS: The protocol design derived from a schedule
      optimized preclinical regimen. Drugs were administered together, and also with
      thermal therapy in a schedule that optimized the therapeutic index. Eligible
      patients were those with therapy-resistant, metastatic or advanced solid
      malignancies. Beginning at 40 mg/m(2), the cisplatin dose was escalated by 10
      mg/m(2) to the maximally tolerated dose (MTD) in successive cohorts of 3
      patients. A treatment cycle consisted of cisplatin on day one, followed by
      thermal therapy and simultaneous gemcitabine 36 hours later; then a second dose
      of gemcitabine one week later; and daily IFN- alpha. RESULTS: Thirty-seven
      patients were treated on protocol. The MTD of cisplatin in the thermochemotherapy
      regimen was established to be 60 mg/m(2). The dose limiting toxicities (DLT) were
      peripheral neuropathy and ototoxicity. Complete and partial responses combined
      were 43%. The therapy improved the quality of life of responding patients.
      CONCLUSION: The protocol was well tolerated and was associated with antitumor
      activity in patients with a variety of advanced metastatic solid tumors. Tumor
      response occurred with the thermochemotherapy treatment despite treating
      malignancies that had progressed on the same chemotherapy drugs administered as
      standard treatment. Notably, good responses were observed in patients with high
      grade neuroendocrine and pancreas cancers. This regimen will be tested in a phase
      II study.

PMID- 18608596
TI  - Survey of complementary and alternative therapies used by children with specific
      learning difficulties (dyslexia).
AB  - BACKGROUND: Dyslexia is a common learning difficulty affecting up to 10% of
      British children that is associated with a wide range of cognitive, emotional and
      physical symptoms. In the absence of effective conventional treatment, it is
      likely that parents will seek complementary and alternative medicine (CAM) to try
      and help their children. However, little is known about the level of CAM use or
      the type of CAM used by dyslexic children. AIMS: This study assessed: (1) the
      lifetime use of CAM by dyslexic children, (2) the role of socio-demographic
      factors in CAM use by dyslexic children, (3) parental attitudes towards CAM use
      in the treatment of dyslexia, and (4) how parents' understanding of dyslexia
      affects CAM use. METHODS & PROCEDURES: A semi-structured questionnaire-based
      survey of parents of 148 dyslexic school children was undertaken. The children
      had been recruited to a university research programme investigating the
      effectiveness of a complementary therapy for the treatment of learning
      difficulties. OUTCOMES & RESULTS: Lifetime use of CAM was 55.4% (82 children).
      The most popular CAM approaches were nutritional supplements/special diets (63
      children) followed by homeopathy (29 children) and osteopathy/chiropractic
      manipulation (29 children). Socio-demographic factors did not predict CAM use. In
      total, parents of 101 dyslexic children reported that an interest in CAM for the
      treatment of dyslexia was based on their preference for CAM for their families
      more generally. Parents who thought that dyslexia was a 'medical/health' disorder
      were more likely to have used CAM with their children (p<0.01) than other parents
      in this survey. CONCLUSIONS & IMPLICATIONS: Educational and health professionals
      should be aware that many dyslexic children use CAM. Parents of dyslexic children
      should be provided with evidence-based advice to help them make informed
      therapeutic choices.

PMID- 18608601
TI  - Voices of young people with a history of specific language impairment (SLI) in
      the first year of post-16 education.
AB  - BACKGROUND: Giving young people more and better opportunities to have their
      voices heard is a key feature of current educational policy and research
      internationally and in the UK. AIMS: To examine the views of young people with a
      history of specific language impairment (SLI) as they entered post-16 education.
      METHODS & PROCEDURES: A total of 54 students identified as having SLI at 8 years
      of age were followed up through primary and secondary school to post-16
      destinations. Most had been educated in mainstream schools. The young people were
      interviewed individually in relation to their perceptions of their special
      educational needs, their views on service provision, the role of family and
      friends as support systems, and their aspirations and barriers to future
      education at the early stages of post-16 education, training and work. OUTCOMES &
      RESULTS: The young people were able to offer accurate accounts of their history
      of special educational needs and to explore issues related to their development.
      Most young people were aware of the specific difficulties they experienced and
      had positive views about the support offered to them during their schooling. All
      the young people had at least one person in their family or friendship circle to
      whom they could talk about their joys and concerns, and friendships were an
      important and positive element in their lives. Additionally, most had a positive
      view of their post-16 courses, with comparable numbers hoping to undertake
      further study or training, or to go into work. They also had optimistic hopes for
      their futures five years ahead. CONCLUSIONS: The current study has demonstrated
      that young people with a history of SLI have an awareness of their difficulties
      and of the impact that these needs have on different aspects of their lives. They
      were also able to provide valuable views of service provision, both in terms of
      evaluating the support they received and suggesting ways of improving it.
      Ascertaining the views of younger children with SLI and including them in
      decision-making about their education and lives should be an important aspect of
      the role of those professionals working with this group of children. The study
      supports the importance of gaining the views of young people with SLI not only as
      a matter of rights, but also for the practical benefits that can ensue.

PMID- 18608602
TI  - Specific language impairment and school outcomes. II: Educational context,
      student satisfaction, and post-compulsory progress.
AB  - BACKGROUND: This investigation is the second paper of a companion set reporting
      the outcomes of secondary schooling for young people who have been participating
      in the Manchester Language Study. AIMS: To examine the school context of
      educational results at 16 years of age and to provide information on the
      adolescents' post-16 activities. METHODS & PROCEDURES: A total of 120 adolescents
      with a history of specific language impairment (SLI) and 121 adolescents with
      typical development (TD) in their final year of compulsory secondary schooling
      (mean age = 17;4 years) participated in the study. Data on educational placement,
      special education support and provision of statement of special educational needs
      (SEN) were collected, along with the provision of access arrangements during
      examinations. Adolescents were interviewed about their levels of expectation and
      satisfaction with their examination results and their subsequent post-16
      activities. OUTCOMES & RESULTS: Only a small proportion of adolescents attended
      special units/schools throughout their secondary schooling; a larger proportion
      consistently attended mainstream schools. Those in receipt of a statement of SEN
      performed more poorly in their examinations than those without a statement.
      Around 60% of the adolescents with SLI were provided with some type of access
      arrangements during their core examinations. The majority (88%) of adolescents
      with SLI reported that they were satisfied with their educational outcomes. Most
      adolescents with SLI (91%), regardless of school placement at 16 years, remained
      in education post-16, with the majority in college settings. CONCLUSIONS:
      Adolescents with a history of SLI have continued difficulties throughout
      secondary schooling, with three-quarters of the sample receiving some form of
      special education in a variety of settings. Educational attainment varied across
      different groups of adolescents but was consistently poorer than the attainment
      of typically developing peers. Young people with SLI in the 2000s appear to have
      more opportunities to remain in education post-16 than they did in the 1990s.

PMID- 18608603
TI  - Simple View of Reading in Down's syndrome: the role of listening comprehension
      and reading skills.
AB  - BACKGROUND: According to the 'Simple View of Reading' (Hoover and Gough 1990),
      individual differences in reading comprehension are accounted for by decoding
      skills and listening comprehension, each of which makes a unique and specific
      contribution. AIMS: The current research was aimed at testing the Simple View of
      Reading in individuals with Down's syndrome and comparing their profiles with
      typically developing first graders. METHODS & PROCEDURES: Listening comprehension
      and the ability to read both words and non-words was compared in two groups with
      the same level of reading comprehension: 23 individuals with Down's syndrome aged
      between 11 years 3 months and 18 years 2 months and 23 first-grade typically
      developing children aged between 6 years 2 months and 7 years 4 months. OUTCOMES
      & RESULTS: The results indicate that at the same level of reading comprehension,
      individuals with Down's syndrome have less developed listening comprehension and
      more advanced word recognition than typically developing first graders. A
      comparison of the profiles of the two groups revealed that reading comprehension
      level was predicted by listening comprehension in both groups of participants and
      by word-reading skills only in typically developing children. CONCLUSIONS &
      IMPLICATIONS: The Simple View of Reading model is confirmed for individuals with
      Down's syndrome, although they do not show the reading profile of typically
      developing first graders; rather, they show an atypical profile similar to that
      of 'poor comprehenders' (Cain and Oakhill 2006). The crucial role of listening
      comprehension in Down's syndrome is also discussed with reference to the
      educational implications.

PMID- 18608604
TI  - Specific language impairment and school outcomes. I: identifying and explaining
      variability at the end of compulsory education.
AB  - BACKGROUND: This investigation reports the results of national educational
      examinations in secondary schooling for young people who have been participating
      in the Manchester Language Study. AIMS: The emphasis of the study is on
      furthering understanding of educational outcomes at the end of compulsory
      education. METHODS & PROCEDURES: A total of 120 adolescents with a history of
      specific language impairment (SLI) and 121 adolescents with typical development
      (TD) who were in their final year of compulsory secondary schooling (mean age =
      17;4 years) participated. National educational examination results throughout
      secondary schooling were collected along with a range of psycholinguistic skills
      from 11 to 16/17 years. OUTCOMES & RESULTS: Forty-four per cent of young people
      with SLI obtained at least one of the expected qualifications at the end of
      secondary education, indicating some improvements compared with reports on
      earlier cohorts. Regression analyses revealed that literacy and language skills
      were predictive of educational attainment after controlling for IQ and maternal
      education. Nearly one-quarter of the sample of adolescents with SLI was not
      entered for any examinations at the end of compulsory education. A very strong
      association between earlier patterns of entry for examinations and patterns of
      examination entry at school leaving age was found. CONCLUSIONS: In addition to
      performance IQ, concurrent and early literacy and language skills have
      significant effects on the academic attainments of young people with a history of
      SLI. The transition from primary to secondary schooling is a crucial time for
      assessment and evaluation of individual children's needs and levels of support
      required.

PMID- 18608605
TI  - Increasing prevalence of specific language impairment (SLI) in primary healthcare
      of a Finnish town, 1989-99.
AB  - BACKGROUND: The increasing prevalence of specific language impairment (SLI) is a
      matter of current debate. AIMS: Speech and language therapists and other
      authorities in Finland have discussed the prevalence of SLI since the 1990s. This
      discussion has been based on international studies because of the lack of
      national studies. This paper presents the first Finnish prevalence study of SLI
      in primary healthcare and, thus, participates in the international discussion on
      the prevalence of SLI. Furthermore, two samples of delayed language development
      (DLD) were studied. METHODS & PROCEDURES: This is a retrospective study from 1989
      1999. It was conducted on the population of one of the biggest towns in Finland,
      and was collected from the statistical records of speech and language therapists.
      OUTCOMES & RESULTS: The prevalence of SLI increased, and this increase was
      statistically significant. The prevalence of SLI was less than 1% in age group 0
      6 years and, thus, presents a much lower prevalence than international discussion
      has suggested. SLI seems to be present particularly in boys though it was also
      increasing in girls. Furthermore, children with SLI seem to be more affected by
      receptive difficulties over the period studied. Particularly important is the
      observation that the prevalence of DLD was also increasing, and together with SLI
      they suggest a prevalence rate of 2.5% in Finland. CONCLUSIONS: The low
      prevalence of SLI in this study might be a consequence of the path of
      intervention that effectively separates SLI from delayed language development.
      Furthermore, the questions of language specific features needs to be emphasized.
      The findings of this study suggest that the prevalence of SLI increased as did
      the prevalence of DLD. The range of prevalence estimates of SLI in different
      studies raises the need for national and international epidemiological studies of
      SLI with equal criteria of assessment in each language.

PMID- 18608606
TI  - Environmental factors that influence communication between people with
      communication disability and their healthcare providers in hospital: a review of
      the literature within the International Classification of Functioning, Disability
      and Health (ICF) framework.
AB  - The importance of effective healthcare communication between healthcare providers
      and people needing healthcare is well established. People with communication
      disabilities are at risk of not being able to communicate effectively with their
      healthcare providers and this might directly compromise their health, healthcare
      and their right to participate actively in decisions about their healthcare. This
      paper reviews the literature on the environmental factors that influence
      communication between adults with communication disabilities and their healthcare
      providers in the acute hospital setting within the framework of the World Health
      Organization's International Classification of Functioning, Disability and Health
      (ICF) (2001). It focuses in particular on the environmental factors that
      facilitate or create barriers for people with communication disabilities because
      environmental factors can be modified so that acute care hospitals can become
      more accessible communicative environments for all people. The paper describes
      the particular environmental factors that have been identified in acute hospitals
      that influence the ability of people with specific types of communication
      disabilities and their healthcare providers to communicate. It then goes on to
      describe the common environmental factors that have been identified across people
      with different types of communication disabilities when they are communicating
      with their healthcare providers. This paper concludes with suggestions for
      directions of future research.

PMID- 18608607
TI  - Investigating the psycholinguistic correlates of speechreading in preschool age
      children.
AB  - BACKGROUND: Previous research has found that newborn infants can match phonetic
      information in the lips and voice from as young as ten weeks old. There is
      evidence that access to visual speech is necessary for normal speech development.
      Although we have an understanding of this early sensitivity, very little research
      has investigated older children's ability to speechread whole words. AIMS: The
      aim of this study was to identify aspects of preschool children's linguistic
      knowledge and processing ability that may contribute to speechreading ability. We
      predicted a significant correlation between receptive vocabulary and
      speechreading, as well as phonological working memory to be a predictor of
      speechreading performance. METHODS & PROCEDURES: Seventy-six children (n = 76)
      aged between 2;10 and 4;11 years participated. Children were given three pictures
      and were asked to point to the picture that they thought that the experimenter
      had silently mouthed (ten trials). Receptive vocabulary and phonological working
      memory were also assessed. The results were analysed using Pearson correlations
      and multiple regressions. OUTCOMES & RESULTS: The results demonstrated that the
      children could speechread at a rate greater than chance. Pearson correlations
      revealed significant, positive correlations between receptive vocabulary and
      speechreading score, phonological error rate and age. Further correlations
      revealed significant, positive relationships between The Children's Test of Non
      Word Repetition (CNRep) and speechreading score, phonological error rate and age.
      Multiple regression analyses showed that receptive vocabulary best predicts
      speechreading ability over and above phonological working memory. CONCLUSIONS &
      IMPLICATIONS: The results suggest that preschool children are capable of
      speechreading, and that this ability is related to vocabulary size. This suggests
      that children aged between 2;10 and 4;11 are sensitive to visual information in
      the form of audio-visual mappings. We suggest that current and future therapies
      are correct to include visual feedback as a therapeutic tool; however, future
      research needs to be conducted in order to elucidate further the role of
      speechreading in development.

PMID- 18608608
TI  - Intelligibility of dysarthric speech: perceptions of speakers and listeners.
AB  - BACKGROUND: Many factors influence listener perception of dysarthric speech.
      Final consensus on the role of gender and listener experience is still to be
      reached. The speaker's perception of his/her speech has largely been ignored.
      AIMS: (1) To compare speaker and listener perception of the intelligibility of
      dysarthric speech; (2) to explore the role of gender and listener experience in
      speech perception; and (3) to examine the relationship between speaker
      perceptions of intelligibility and formal clinical intelligibility ratings.
      METHODS & PROCEDURES: Study 1 examines listener perception of intelligibility of
      dysarthric speech. Twenty people with acquired dysarthria, ten speech language
      therapists (SLTs) and 20 naive listeners heard audio recordings of dysarthric
      speech and used direct magnitude estimation (DME) to rate perceptions of speech
      intelligibility. Differences in perception across gender and listener experience
      (SLTs versus naive listeners) were examined. Study 2 tackles the speaker's
      perception of his/her own speech intelligibility. Using the same groups of
      participants and DME, speakers rated their own speech intelligibility. SLTs and
      naive listeners then rated their perception of the speakers' intelligibility.
      Differences in perceptions between speakers and listeners were compared. Further
      analysis examined differences across gender and listener experience. Finally,
      ratings of speakers' perception of their own intelligibility were compared with
      intelligibility scores on the Assessment of Intelligibility of Dysarthric Speech
      (ASSIDS) (1981). OUTCOMES & RESULTS: Study 1 showed no statistically significant
      differences in perception of intelligibility across the three listener groups,
      although results suggest that speakers rate perceptions of intelligibility
      differently to SLTs and naive listeners. Despite some individual differences in
      ratings between speakers and listeners in Study 2, overall there are no
      significant group differences and methodological limitations to this section of
      the study are highlighted. In Studies 1 and 2 there are no statistically
      significant differences across gender and listener experience, although SLTs are
      less consistent in their ratings of speech when compared with naive listeners.
      There is no statistically significant relationship between formal intelligibility
      assessment scores and the speakers' perception of intelligibility. CONCLUSIONS:
      This study contributes to an understanding of perceptions of dysarthric speech.
      The lack of gender differences in listener perception supports earlier findings
      in other areas of SLT. The strong relationship between SLT and naive listeners'
      perceptions suggests that SLTs are not more critical of dysarthric speech. The
      discrepancy between formal assessment measures and speakers' perceptions of
      intelligibility has implications for clinical practice. The need for further
      research in the area is highlighted.

PMID- 18608609
TI  - Effects of 'Context-Optimization' on the acquisition of grammatical case in
      children with specific language impairment: an experimental evaluation in the
      classroom.
AB  - BACKGROUND: Disorders in the acquisition of morphological agreement phenomena,
      e.g. case marking, are characteristic of German children with specific language
      impairment (SLI). Although the success of individual therapy has already been
      documented, there are general doubts about the success of grammar facilitation in
      the classroom. AIMS: To investigate whether children with SLI, who were trained
      with the new program 'Context-Optimization' during classes, achieved significant
      improvements in the acquisition of case and whether this therapeutic approach was
      more effective than the traditional methods used in a control group. METHODS &
      PROCEDURES: Forty-five classes of 19 special language schools participated in the
      study. Within 12 weeks the experimental group, consisting of 63 children,
      received 12 hours of therapy during their lessons. The therapeutic measures were
      implemented directly by their class teachers, who are additionally qualified as
      school speech and language pathologists. The case marking skills of the 63
      children constituting the control group were also trained during classes or
      within individual or group therapy, although their teachers used other methods
      than Context-Optimization. OUTCOMES & RESULTS: The experimental group
      participants increased their case-marking skills significantly, even after a
      short-term intervention, and these effects remained stable. It is evident that
      their improvements were independent of any risk factors such as deficits in the
      perception and processing of language, problems in gender agreement and
      bilingualism. Context-Optimization therapy in the classroom is effective for both
      accusative and dative, the prominent therapy goal, while traditional methods are
      only effective for accusative. CONCLUSIONS: A critical analysis of the data
      reveals two important implications for future interventions: (1) the reduction of
      language material to ensure proper use of gender during therapy sequences; and
      (2) the adaptation of therapeutic steps to the learning tempo of the pupils.

PMID- 18608610
TI  - Extended follow-up of a randomized controlled trial of the Lidcombe Program of
      Early Stuttering Intervention.
AB  - BACKGROUND: In the Lidcombe Program of Early Stuttering Intervention, parents
      present verbal contingencies for stutter-free and stuttered speech in everyday
      situations. A previous randomized controlled trial of the programme with
      preschool-age children from 2005, conducted in two public speech clinics in New
      Zealand, showed that the odds of attaining clinically minimal levels of
      stuttering 9 months after randomization were more than seven times greater for
      the treatment group than for the control group. AIMS: To follow up the children
      in the trial to determine extended long-term outcomes of the programme. METHODS &
      PROCEDURES: An experienced speech-language therapist who was not involved in the
      original trial talked with the children on the telephone, audio recording the
      conversations using a telephone recording jack. Parental reports were gathered in
      addition to the children's speech samples in order to obtain a balance of
      objective data and reports from a wide range of situations. OUTCOMES & RESULTS:
      At the time of this follow-up, the children were aged 7-12 years, with a mean of
      5 years post-randomization in the 2005 trial. Twenty of the 29 children in the
      treatment arm and eight of the 25 children in the control (no treatment) arm were
      able to be contacted. Of the children in the treatment group, one (5%) failed to
      complete treatment and 19 had completed treatment successfully and had zero or
      near-zero frequency of stuttering. Three of the children (16%) who had completed
      treatment successfully had relapsed after 2 or more years of speech that was
      below 1% syllables stuttered. Meaningful comparison with the control group was
      not possible because an insufficient number of control children were located and
      some of them received treatment after completing the trial. CONCLUSIONS &
      IMPLICATIONS: The majority of preschool children are able to complete the
      Lidcombe Program successfully and remain below 1% syllables stuttered for a
      number of years. However, a minority of children do relapse and will require
      their parents to reinstate the treatment procedures.

PMID- 18608611
TI  - Health-related quality of life in people with severe aphasia.
AB  - BACKGROUND: Health-related quality of life (HRQL) measures are increasingly used
      to help us understand the impact of disease or disability on a person's life and
      to measure the effectiveness of interventions. A small number of studies have
      looked at perceived HRQL in people with mild or moderate aphasia. They report
      that reduced HRQL is associated with low psychological well-being and depression,
      reduced activity levels and high levels of communication disability. Still, very
      little is known about the quality of life of people with severe aphasia. AIMS:
      This study aimed to evaluate the HRQL of people with severe aphasia as rated by
      their proxy respondents. To increase our understanding of these proxy
      evaluations, the findings were compared with those of two other studies of HRQL
      in people with moderate or mild aphasia, using proxy and self-report respondents.
      METHODS & PROCEDURES: A questionnaire-based cross-sectional survey was carried
      out where proxies of people with severe aphasia reported on their HRQL. The
      people with severe aphasia who took part in this study were part of a larger
      cohort of people with aphasia who were able to self-report on their HRQL. Aphasia
      was assessed with the American Speech and Hearing Association Functional
      Assessment of Communication Skills for Adults (ASHA-FACS) and the Frenchay
      Aphasia Screening Test (FAST) and HRQL with the Stroke and Aphasia Quality of
      Life (SAQOL) scale (proxy-reported). SAQOL-39 scores were derived from the SAQOL.
      RESULTS & RESULTS: People with severe aphasia's quality of life, as measured by
      their proxies (n = 12), was low and more than one standard deviation below that
      of the standardization sample of the SAQOL. The overall mean score for the SAQOL
      39 and the means for its physical and communication domains were below the 20th
      centile. They were also significantly lower that those of the comparison studies
      of self-reports (n = 83) and proxy ratings (n = 50) of people with mild or
      moderate aphasia (p<or=0.003). In the comparison studies there were no
      significant differences between the self-report and proxy ratings of people with
      mild or moderate aphasia. CONCLUSIONS & IMPLICATIONS: This small study suggests
      that the HRQL of people with severe aphasia, as reported by their proxies, is
      severely compromised. Further research, using a wide range of methodologies, is
      needed in order to address the challenge of understanding better the quality of
      life of people with severe aphasia.

PMID- 18608612
TI  - Language profiles of monolingual and bilingual Finnish preschool children at risk
      for language impairment.
AB  - BACKGROUND: A large proportion of children are exposed to more than one language,
      yet research on simultaneous bilingualism has been relatively sparse.
      Traditionally, there has been concern that bilingualism may aggravate language
      difficulties of children with language impairment. However, recent studies have
      not found specific language impairment (SLI) or language-related problems to be
      increased by bilingualism. AIMS: The topic of bilingualism and its effects has
      high actuality in Finland, where increasing numbers of children in the country's
      6% Swedish-speaking minority grow up in bilingual families, where one parent's
      primary language is Swedish and the other's Finnish. The present study aimed at
      exploring the influence of such bilingualism on the language profiles of children
      from this population at risk for language impairment (LI). METHODS & PROCEDURES:
      Participants were recruited from a language screening of 339 children from
      kindergartens with instruction only in Swedish, from the Swedish-speaking parts
      of Finland. Of these children, 33 (9.7%) were defined as a Risk Group for LI,
      whereas 48 non-risk children were randomly selected to form a control group. When
      subdividing the children according to home language, 35 were found to be
      monolingual, Swedish-speaking, and 46 were Swedish-Finnish bilingual. The
      children underwent neuropsychological assessment during their preschool year.
      Assessment methods included subtests from the Wechsler Primary and Preschool
      Scale of Intelligence - Revised and the NEPSY Developmental Neuropsychological
      Assessment. OUTCOMES & RESULTS: A repeated-measures multiple analysis of
      covariance (MANCOVA) showed a significant effect of risk of LI on the NEPSY
      language scores. The effect of home language was not significant and there was no
      interaction between home language and risk for LI. Non-verbal IQ was controlled
      for. Across groups, bilingual children scored lower than monolingual children
      only on measures of vocabulary and sentence repetition. CONCLUSIONS: Although a
      slight general cost of bilingualism was found in the language profile of the six
      year olds in this study, a bilingual background was not associated with more
      severe language problems in the LI Risk Group. Thus, there would seem to be no
      need to shield language-impaired children from opportunities for dual language
      learning.

PMID- 18608613
TI  - Perceptions of speech-pathology and audiology students concerning death and
      dying: a preliminary study.
AB  - BACKGROUND: Formal training in dealing with death and dying issues is not a
      standard content area in communication sciences and disorders programmes'
      curricula. At the same time, it cannot be presumed that pre-professional
      students' personal background equips them to deal with these issues. AIM: To
      investigate the perceptions of pre-professional speech-language pathology and
      audiology students' need for formal training in death and dying issues. METHODS &
      PROCEDURES: Participants were 230 undergraduate and graduate students enrolled in
      communication sciences and disorders courses in a southern, metropolitan
      university, in the USA. A questionnaire developed by the researchers was given.
      Post-hoc analyses were conducted. OUTCOMES & RESULTS: Results indicated that
      participants desired training in the area of death and dying before entering the
      professional world, even though they rated themselves to be fairly knowledgeable
      about the topic. Preferred methods for acquiring knowledge about death and dying
      were personal and professional experiences, followed by consulting professional
      resources, classroom instruction, and talking to professionals who are familiar
      with death and dying. CONCLUSIONS: Education in death and dying is needed by pre
      professional, speech-language pathology and audiology students who appear to be
      at risk for professional obstacles and emotional trauma from the death of their
      patients.

PMID- 18608616
TI  - Quality of phonological representations: a window into the lexicon?
AB  - BACKGROUND: There is a great deal of evidence to support the robust relationship
      between phonological awareness and literacy development. Researchers are
      beginning to understand the relationship between the accuracy and distinctiveness
      of stored phonological representations and performance on phonological awareness
      tasks. However, many of the tasks currently used to assess the integrity of
      underlying representations are confounded by requiring spoken output. AIMS: This
      paper describes the development of the Quality of Phonological Representations
      (QPR) task, a task that does not require speech output, and its evaluation in the
      context of a larger study examining predictors of literacy outcomes in Western
      Australia. METHODS & PROCEDURES: The QPR task was given as part of a larger task
      battery to a cohort of 235 mainstream children in the last term of their
      Preprimary year (average age = 5;5) and to 179 children at follow-up at the end
      of Year 2 (average age = 7;9). OUTCOMES & RESULTS: Normative data for both
      accuracy and reaction time are presented in percentile tables (appendix B). In
      their Preprimary year, children were able to identify correct productions of
      multi-syllabic words (hits) on average 87.5% of the time, rising to an average of
      93.8% in Year 2. As expected, children became quicker at making these judgements,
      reaction time shifting from an average of 1.1 s in Preprimary to 0.83 s in Year
      2. A similar pattern was observed with the data for correct rejections. To make
      these judgements, the children had to identify a pseudo-word as an incorrect
      pronunciation by 'Katie the computer'. In the Preprimary year, children were able
      to reject correctly the pseudo-words on average 68.5% of the time, rising to an
      average of 81.7% in Year 2. As expected, children became quicker at making these
      judgements, reaction time shortening from an average of 1.4 s in Preprimary to
      0.81 s in Year 2. The QPR task was shown to have moderate reliability and
      concurrent validity. CONCLUSIONS: The QPR task appears to be a useful and cost
      effective addition to task batteries aiming to identify at-risk children in the
      early stages of schooling. The ability to profile children's phonological
      awareness skills and gain insight into their underlying phonological
      representation skills allows more informed goal setting and intervention
      planning.

PMID- 18608623
TI  - Family Weight School treatment: 1-year results in obese adolescents.
AB  - OBJECTIVE: The aim was to evaluate the efficacy of a Family Weight School
      treatment based on family therapy in group meetings with adolescents with a high
      degree of obesity. METHODS: Seventy-two obese adolescents aged 12-19 years old
      were referred to a childhood obesity center by pediatricians and school nurses
      and offered a Family Weight School therapy program in group meetings given by a
      multidisciplinary team. Intervention was compared with an untreated waiting list
      control group. Body mass index (BMI) and BMI z-scores were calculated before and
      after intervention. RESULTS: Ninety percent of the intervention group completed
      the program (34 boys, 31 girls; baseline age = 14.8 +/- 1.8 years [mean +/-
      standard deviation, SD], BMI = 34 +/- 4.0, BMI z-score = 3.3 +/- 0.4). In the
      control group 10 boys and 13 girls (baseline age = 14.3 +/- 1.6, BMI = 34.1 +/-
      4.8, BMI z-score = 3.2 +/- 0.4) participated in the 1-year follow-up. Adolescents
      in the intervention group with initial BMI z-score < 3.5 (n = 49 out of 65,
      baseline mean age = 14.8, mean BMI = 33.0, mean BMI z-score = 3.1), showed a
      significant decrease in BMI z-scores in both genders (-0.09 +/- 0.04, p = 0.039)
      compared with those in the control group with initial BMI z-score < 3.5 (n = 17
      out of 23, mean baseline age = 14.1, mean baseline BMI = 31.6, mean baseline BMI
      z-score = 3.01). No difference was found in adolescents with BMI z-scores > 3.5.
      CONCLUSIONS: Family Weight School treatment model might be suitable for
      adolescents with BMI z-score < 3.5 treated with a few sessions in a
      multidisciplinary program.

PMID- 18608625
TI  - Sleep-disordered breathing and systemic inflammation in overweight children and
      adolescents.
AB  - OBJECTIVE: To assess if the severity of sleep-disordered breathing (SDB) and
      mainly intermittent hypoxia is associated with increased peripheral leukocytes in
      overweight children and adolescents, controlling for adiposity and obesity
      related metabolic abnormalities. METHODS: Consecutive subjects were recruited at
      a pediatric obesity clinic. All subjects underwent polysomnography and a fasting
      blood sample. RESULTS: In total, 95 subjects were included (<age> =11.1+/-2.6, 43
      boys, body mass index, <BMI z-score>=2.3+/-0.5, 29 subjects were overweight and
      66 obese). Total white blood cell count increased significantly by worsening of
      intermittent hypoxia. Total white blood cell count was correlated with the
      maximal degree of desaturation, independent of puberty, HOMA and HDL-cholesterol.
      Neutrophil levels were associated with the degree of desaturation, while
      controlling for puberty and HOMA. CONCLUSION: This study supports the hypothesis
      of an independent interaction between intermittent hypoxia and nocturnal
      desaturation during sleep, and increased white blood cell and neutrophil levels
      in overweight and obese children and adolescents. This finding may contribute to
      the mechanisms linking SDB with increased cardiovascular morbidity.

PMID- 18608630
TI  - Neighbourhood fast food outlets and obesity in children and adults: the CLAN
      Study.
AB  - OBJECTIVE: We examined associations between density of and proximity to fast food
      outlets and body weight in a sample of children (137 aged 8-9 years and 243 aged
      13-15 years) and their parents (322 fathers and 362 mothers). METHODS: Children's
      measured and parents' self-reported heights and weights were used to calculate
      body mass index (BMI). Locations of major fast food outlets were geocoded.
      Bivariate linear regression analyses examined associations between the presence
      of any fast food outlet within a 2 km buffer around participants' homes, fast
      food outlet density within the 2 km buffer, and distance to the nearest outlet
      and BMI. Each independent variable was also entered into separate bivariate
      logistic regression analyses to predict the odds of being overweight or obese.
      RESULTS: Among older children, those with at least one outlet within 2 km had
      lower BMI z-scores. The further that fathers lived from an outlet, the higher
      their BMI. Among 13-15-year-old girls and their fathers, the likelihood of
      overweight/obesity was reduced by 80% and 50%, respectively, if they had at least
      one fast food outlet within 2 km of their home. Among older girls, the likelihood
      of being overweight/obese was reduced by 14% with each additional outlet within 2
      km. Fathers' odds of being overweight/obese increased by 13% for each additional
      kilometre to the nearest outlet. CONCLUSIONS: While consumption of fast food has
      been shown to be associated with obesity, this study provides little support for
      the concept that exposure to fast food outlets in the local neighbourhood
      increases risk of obesity.

PMID- 18608631
TI  - Waist circumference as a measure of trunk fat mass in children aged 3 to 5 years.
AB  - OBJECTIVE: The increasing prevalence of obesity in young children emphasises the
      need for accurate measures of total and regional fat at this age. Thus the aim of
      this study was to evaluate the ability of waist circumference, waist-to-height
      ratio (WHtR) and the conicity index (CI) to discriminate between children with
      low and high levels of trunk fat mass. METHODS: Trunk fat mass was measured by
      dual-energy x-ray absorptiometry (DXA) in 301 predominantly Caucasian children
      (150 girls) aged 3-5 years. High trunk fat was defined as an internal z-score of
      > or =+1. Receiver-operating characteristic (ROC) curves and the areas under each
      curve (AUC) were constructed to compare the relative ability of waist
      circumference, WHtR and CI to identify children with low and high trunk fat mass.
      RESULTS: Girls had more truncal fat than boys (P<0.001). AUCs indicated that
      waist circumference correctly discriminated between children with low and high
      trunk fat mass 87% (for girls) to 90% (for boys) of the time. Waist circumference
      performed better than WHtR (AUCs: 0.79 in girls and 0.81 in boys; P=0.164 and
      P=0.011, respectively) and the CI (AUCs: 0.53 in girls and 0.65 in boys,
      P<0.0001). A z-score of 0.55 correctly identified 79% of girls and 81% of boys
      with high trunk fat mass, and 82% of girls and 84% of boys with low trunk fat
      mass. Suggested waist circumference cut-offs for each half-year of age in both
      sexes are reported. CONCLUSION: Waist circumference performs reasonably well as
      an indicator of high trunk fat mass in preschool-aged children.

PMID- 18608632
TI  - Dose-response associations between screen time and overweight among youth.
AB  - OBJECTIVE: To examine dose-response associations between screen time and
      overweight, independent of physical activity and dietary intake. METHODS:
      Participants were 580 Dutch youth (13 years; 48% boys). Body mass index, waist
      circumference and skinfold thickness at four sites determined weight status.
      Questionnaires examined television viewing and computer use, participation in
      organized sport and high caloric snack and sugar-containing beverage consumption.
      RESULTS: There were no significant associations among boys. Compared with girls
      spending less than two hours/day in screen time, those who spent three to four
      hours/day were more likely to be classified as overweight by waist circumference
      (odds ratio [OR]=3.4; 95% confidence intervals [CI]=1.1-10.7; p=0.03), and this
      likelihood increased substantially among those spending more than four hours/day
      (OR=5.5; 95% CI=2.1-14.1; p<or=0.0001). CONCLUSIONS: Girls who spend three or
      more hours/day in screen time are at increased risk of being classified as
      overweight by waist circumference.

PMID- 18608633
TI  - Relationships between weight status and child, parent and community
      characteristics in preschool children.
AB  - OBJECTIVE: To examine, using an Ecological Systems Theoretical framework,
      relationships between weight status and child, parent and community
      characteristics and risk factors among preschool children. METHODS: Cross
      sectional data was collected from 140 children and their parents from 11 randomly
      selected preschools. Outcome variables included: motor development; perceived
      competence; objectively measured physical activity; time spent in active and
      quiet play; location and number of televisions; parental rules around physical
      activity and time spent watching television; availability of sport and physical
      activity programs; and parks and open spaces and access to footpaths. RESULTS:
      Overweight children spent more time in quiet play and watching television and
      less time in active play and physical activity. Perceived competence and motor
      development were similar for both overweight and non-overweight children.
      Associations between weight status and several parent and community
      characteristics were not evident, except for access to footpaths. Overweight
      children had greater access to footpaths compared with non-overweight children
      (p=0.046). CONCLUSION: The results reported here showed little difference between
      overweight and non-overweight children in relation to a variety of child, parent
      and community variables. However, for some characteristics, differences in older
      children have been reported. Longitudinal studies are required to confirm when
      these characteristics begin to differ, what effects these differences have on
      behaviour and weight-status, and therefore when targeted treatment should be
      provided during a child's development.

PMID- 18608634
TI  - Eight-year-old children with high cardiorespiratory fitness have lower overall
      and abdominal fatness.
AB  - OBJECTIVE: 1) To examine whether cardiorespiratory fitness (CRF) is associated
      with waist circumference (WC) and overall and abdominal fatness in eight-year-old
      girls and boys. 2) To determine whether children with high CRF have lower WC,
      overall and abdominal fatness within the same body mass index (BMI) category
      compared with those with low CRF. DESIGN: A cross-sectional study of 304 eight
      year-old children in Tampere, Finland whose parents responded to a postal
      invitation and participated in measurements. MEASUREMENTS: Total body fat
      percentage (BF%), abdominal region fat percentage (AF%), and fat-free mass (FFM)
      were assessed by dual-energy X-ray absorptiometry (DXA). WC, height and weight
      were measured. International BMI sex- and age-specific cut-off points were used
      for overweight and obesity definition, and participants were divided into two
      categories: normal weight or overweight/obese. CRF was assessed with a maximal
      multistage 20-m shuttle run test (20-mSRT). RESULTS: Of the children, 81% were
      normal weight and 19% were overweight/obese. CRF was inversely associated with WC
      (p<0.011), BF% (p<0.001) and AF% (p<0.001) independent of age, sex and BMI.
      Within the same BMI category, children with high CRF had significantly lower WC
      (p=0.001), BF% (p<0.001) and AF% (p<0.001) compared with children with low CRF.
      CONCLUSION: Eight-year-old children with high CRF had lower overall and abdominal
      fatness compared with children with low CRF, independent of age, sex and BMI. CRF
      should be an important target already at a young age in preventing overall and
      abdominal obesity.

PMID- 18608635
TI  - Predictors of fatness and physical fitness in nine-year-old Icelandic school
      children.
AB  - INTRODUCTION: In recent years, the prevalence of overweight and obese children
      has increased in Iceland, as in most Westernized countries. The main objectives
      of this study were to assess predictors of fitness and fatness of 9-year-old
      school children in Iceland. METHODS: In total, 488 subjects (73.3% participation
      rate) from 18 randomly selected primary schools participated in this cross
      sectional study. Height, weight, sum of four skinfolds and other anthropometric
      measures were performed on all children. Fitness was assessed via a maximal cycle
      ergometer test in 229 children and of those, 177 wore Actigraph accelerometers to
      measure physical activity over five consecutive days. Questionnaires regarding
      family background and lifestyle were completed by 361 mothers and 332 fathers.
      RESULTS: The main findings from our study showed fatness, area of living and sex,
      as well as background variables, such as fathers' smoking and income, and number
      of sport practices attended per week were important predictors of fitness (best
      fit model: R-sq=0.48, p<0.0001). In addition, parental body mass index (BMI),
      mothers' smoking and physical activity and children's objective measure of
      physical activity were found to be important predictors of children's fatness
      (best-fit model: R-sq=0.23, p<0.0001). CONCLUSION: These results provide
      information about predictors of fitness and fatness of 9-year-old children and
      emphasize the inverse association between the two. Further, our results suggest
      that mothers have a stronger influence on children's weight than fathers but the
      opposite may be true for fitness.

PMID- 18608636
TI  - Predictors of body mass index change in Australian primary school children.
AB  - OBJECTIVE: To assess associations between multiple potential predictors and
      change in child body mass index (BMI). METHODS: In the 1997 Health of Young
      Victorians Study, children in Grades preparatory to three (aged 5-10 years) had
      their height and weight measured. Parents provided information on potential
      predictors of childhood overweight across six domains (children's diet,
      children's activity level, family composition, sociodemographic factors, prenatal
      factors and parental adiposity). Measures were repeated three years later in
      2000/1. BMI was transformed to standardised (z) scores using the US 2000 Growth
      Chart data and children were classified as non-overweight or overweight according
      to international cut-points. Regression analyses, including baseline BMI z-score
      as a covariate, assessed the contribution of each potential predictor to change
      in BMI z-score, development of overweight and spontaneous resolution of
      overweight in 1,373 children. RESULTS: BMI z-score change was positively
      associated with frequency of take-away food, food quantity, total weekly screen
      time, non-Australian paternal country of birth, maternal smoking during
      pregnancy, and maternal and paternal BMI. Inverse associations were noted for the
      presence of siblings and rural residence (all p<0.05). Predictors of categorical
      change (development and resolution of overweight) were less clearly identified,
      apart from an association between maternal BMI and overweight development
      (p=0.02). Multivariable models suggested individual determinants have a
      cumulative effect on BMI change. CONCLUSIONS: Strong short-term tracking of BMI
      makes it difficult to identify predictors of change. Nonetheless, putative
      determinants across all domains assessed were independently associated with
      adiposity change. Multi-faceted solutions are likely to be required to
      successfully deal with the complexities of childhood overweight.

PMID- 18608637
TI  - Rural Canadian adolescents are more likely to be obese compared with urban
      adolescents.
AB  - OBJECTIVE: Few studies have examined variations in overweight and obesity by
      geographic location in youth. The purpose of this study was to investigate the
      association between urban/rural geographic status and being overweight or obese
      among Canadian adolescents. METHODS: The study involved an analysis of a
      representative sample of 4851 Canadian adolescents in grades 6 to 10 from the
      2001-02 Health Behaviour in School-aged Children Survey. Self-reports of
      participants' demographics, physical activity, screen time, diet, and body mass
      index (BMI) were assessed. Adiposity status was determined using the
      international BMI thresholds for children and youth. Urban/rural status was coded
      on a five-point scale based on the geographic location of the participants'
      schools. Logistic regression with generalized estimating equations to adjust for
      clustering was used to examine the association between urban/rural status and
      overweight/obesity. RESULTS: The population was 53.3% female with a mean age of
      13.9 years (standard deviation, SD=1.5). Approximately 22.2% were living in rural
      areas while 14.4% were living in large metropolitan (metro) areas. After
      adjusting for age, sex, socioeconomic status, and Region of Canada, there was a
      trend for increasing overweight (p=0.001) and obesity (p=0.03) among adolescents
      as the level of "rurality" increased (relative odds for most urban to most rural
      regions for overweight or obese: 1.00, 0.98, 1.18, 1.57, 1.36; obesity: 1.00,
      1.06, 1.39, 1.58, 1.56). Conclusion. This study provides new information about
      patterns of overweight/obesity among Canadian adolescents by urban-rural
      geographic status. These findings suggest that obesity prevention interventions
      should be particularly aggressive in rural areas.

PMID- 18608638
TI  - Waist-to-height ratio is correlated with height in US children and adolescents
      aged 2-18 years.
AB  - The waist-to-height ratio is an anthropometric measure of central adiposity that
      has emerged as a significant predictor of cardiovascular disease risk factors in
      children and adolescents. However, the simple waist-to-height ratio retains
      residual correlation with height, which could cause the measure to over- or under
      adjust for the effect of height at certain ages. We investigated the dependence
      of waist-to-height ratio on height in the representative US National Health and
      Nutrition Examination Survey 1999-2004. We stratified 11 270 subjects aged 2-18
      years by age and sex. There was considerable residual correlation between height
      and the waist-to-height ratio, ranging from -0.29 to 0.36. Thus, simply dividing
      waist circumference by height (WC/Ht1) might not be appropriate to "adjust for
      height" during periods of growth. We fitted a log-log regression of waist
      circumference on height to determine which exponent for height ensures that the
      log of the ratio is uncorrelated with the log of height, which we call the
      optimal exponent for WC/Ht(p). This optimal power for height in the age- and sex
      specific waist-to-height ratio varies from 0.5 to 2.0, with similar patterns for
      males and females. The value peaks at age 8, and is close to 1 at age 18. Future
      research should investigate how this affects relationships between central
      adiposity and cardiovascular disease risk factors across these ages, and how
      using a power other than 1 might reduce bias and improve precision.

PMID- 18608639
TI  - Central adiposity in 9- and 15-year-old Swedish children from the European Youth
      Heart Study.
AB  - The aim of this study was to provide percentile values for several indices of
      central adiposity in 9- and 15-year-old Swedish children from the European Youth
      Heart Study (N=1,075). Age- and sex-specific percentiles for waist circumference,
      hip circumference, waist-to-height ratio and waist-to-hip ratio were provided. No
      significant differences were found in the proportion of individuals with a high
      waist-to-height ratio (using the 0.500 cut-off) between age or sex groups. The
      percentile values for waist circumference and waist-to-height ratio provided in
      this paper, together with data from other cohorts, could help to establish
      international criteria for defining central obesity. For comparative purposes,
      future studies reporting reference data for waist circumference and/or waist-to
      height ratio, should also report age- and sex-specific height values. More
      studies involving children of different ages and from different regions in
      Scandinavia are needed.

PMID- 18608640
TI  - Double disadvantage: the influence of ethnicity over socioeconomic position on
      childhood overweight and obesity: findings from an inner urban population of
      primary school children.
AB  - OBJECTIVE: To examine the relationship between overweight/obesity in children,
      socioeconomic status and ethnicity/cultural background. DESIGN: Cross-sectional
      survey of children aged 4-13 years. SETTING: A total of 23 primary (elementary)
      schools in an inner urban municipality of Melbourne, Australia. Participants. A
      total of 2685 children aged 4-13 years and their parents. MAIN EXPOSURE MEASURES:
      Ethnicity/cultural background - maternal region of birth; socioeconomic position
      (SEP) indicators - maternal and paternal educational attainment, family
      employment status, possession of a healthcare card, ability to buy food,
      indicator of disadvantage (Socioeconomic Index for Areas, SEIFA) score for
      school; parental weight status. Main outcome measure. Prevalence of
      overweight/obesity. RESULTS: Prevalence of overweight/obesity approached 1 in 3
      (31%) in this sample. Prevalence of overweight/obesity was greater for children
      of both North Africa and Middle Eastern background and children of Southern,
      South Eastern and Eastern European background compared with children of
      Australian background. This difference remained after adjusting for age, sex,
      height, clustering by school, SEP indicators and parental weight status; odds
      ratio, OR=1.57 (95% confidence interval, CI 1.12-2.19) and 1.88 (95%CI 1.24
      2.85), respectively. CONCLUSIONS: There is a clear independent effect of
      ethnicity above and beyond the effect of socioeconomic status on overweight and
      obesity in children. Further research is required to explore the mediators of
      this gradient.

PMID- 18608641
TI  - Relationships between acute reactions to radiotherapy in head and neck cancer
      patients and parameters of radiation-induced DNA damage and repair in their
      lymphocytes.
AB  - PURPOSE: To study the relationship between lymphocyte radiosensitivity measured
      in vitro and acute reactions to radiotherapy in patients with head and neck
      cancer. MATERIALS AND METHODS: Acute reactions were measured in 34 patients using
      the Dische scale. Lymphocyte radiosensitivity was measured using the alkaline
      comet assay, the micronucleus assay, the nuclear division index and morphological
      assessment of apoptosis. RESULTS: There was a weak, statistically significant
      correlation between in vitro radiosensitivity measured as the rate of DNA damage
      repair and the cumulative radiation dose exerting the maximum acute reaction
      scored (r = -0.366, p = 0.039, n = 34). Subgroup analyses showed that for
      patients with a low level of radiation-induced DNA damage there was a
      statistically significant relationship between lymphocyte radiosensitivity
      measured as inhibition of proliferation and acute toxicity (r = -0.621, p =
      0.007, n = 18). For patients with a high level of residual DNA damage, there was
      a relationship between lymphocyte radiosensitivity measured using the
      micronucleus assay and acute toxicity (r = -0.597, p = 0.023, n = 14).
      CONCLUSIONS: Combining two measures of radiosensitivity improves the ability to
      correlate in vitro lymphocyte radiosensitivity and acute radiotherapy toxicity
      data.

PMID- 18608642
TI  - Bone marrow stromal cells spontaneously produce Flt3-ligand: influence of
      ionizing radiations and cytokine stimulation.
AB  - PURPOSE: To define the ability of human bone marrow (BM) stromal cells to produce
      fms-like tyrosine kinase 3 (Flt3)-ligand (FL), and the effect of irradiation,
      tumour necrosis factor-alpha (TNFalpha) or tumour growth factor beta (TGFbeta) on
      FL production. MATERIAL AND METHODS: Primary BM stromal cell cultures were
      irradiated at 2-10 Gy or were stimulated with TNFalpha or TGFbeta1. The presence
      of FL was tested in culture supernatants and in cell lysate. The presence of a
      membrane-bound form of FL and the level of gene expression were also tested.
      RESULTS: Primary BM stromal cells spontaneously released FL. This production was
      increased by TNFalpha but not by TGFbeta1 or by irradiation. Chemical induction
      of osteoblastic differentiation from BM stromal cells also induced an increase in
      FL release. CONCLUSIONS: Our results suggest that the observed increase in FL
      concentration after in vivo irradiation is an indirect effect. The possible
      implication of BM stromal cells in these mechanisms is discussed.

PMID- 18608643
TI  - Assessment of spatial attention and neglect with a virtual wheelchair navigation
      task.
AB  - A total of 9 participants with right-hemisphere stroke performed a new virtual
      reality (VR) wheelchair navigation test of lateralized spatial attention and
      neglect. The test consists of a virtual path along which participants navigate
      (or are navigated) as they name virtual objects encountered. There are 4 VR
      conditions, obtained by crossing the factors array complexity and driver.
      Participants performed the VR task, a real-life wheelchair navigation task, and a
      battery of attention and neglect tests. The VR test showed sensitivity to both
      array complexity and driver, exhibited strong correlations with the wheelchair
      navigation test, and detected lateralized attention deficits in mild patients.
      The VR task thus shows promise as a sensitive, efficient measure of real-life
      navigation.

PMID- 18608644
TI  - Attentional and executive functioning following mild traumatic brain injury in
      children using the Test for Attentional Performance (TAP) battery.
AB  - The interpretation of the data regarding cognitive outcome in children who have
      suffered from mild traumatic brain injury (MTBI) remains currently controversial.
      The aim of the present study is to explore attentional and executive functioning
      in 6-12-year-old children who experienced a MTBI. A total of 15 children with
      MTBI and 15 matched noninjured children participated in the study. Attentional
      tasks using the Test for Attentional Performance battery were administered one
      year after the injury. In comparison to the noninjury children, MTBI children
      performed less accurately on selective attentional and updating tasks. These
      preliminary findings support the view that MTBI can have an impact on specific
      attentional functioning in children one year postinjury.

PMID- 18608645
TI  - Working memory in school-aged children with attention-deficit/hyperactivity
      disorder combined type: are deficits modality specific and are they independent
      of impaired inhibitory control?
AB  - This study examines differences between children with attention-deficit/
      hyperactivity disorder combined type (ADHD-C) and normal controls on verbal and
      visuospatial working-memory (WM) tasks. The extent to which WM deficits in
      children with ADHD-C are independent of impaired inhibitory control was also
      examined. Two groups of 7- to 12-year-old boys participated in this study. The
      first group included 31 boys diagnosed with ADHD-C, and the second group included
      34 boys without ADHD. Various verbal and visuospatial WM tasks and two inhibitory
      control tasks--prepotent response inhibition and interference control--were used.
      Overall, our results suggest impaired verbal and visuospatial WM processes in
      children with ADHD-C, as well as a lower level of performance on prepotent
      response inhibition. WM deficits in ADHD have previously been suggested to be
      particularly salient in the spatial domain; our results instead showed the
      largest effect for a verbal WM task thought to put heavy load on the executive or
      attentional control component of the WM system. An interpretation of this finding
      is that it is variation in terms of difficulty level or load on the executive WM
      processes, rather than variation in modality (verbal versus visuospatial), that
      is important in demonstrating WM deficits in ADHD-C. Finally, findings from
      logistic regression analyses showed that deficits in WM and inhibitory control
      seem to be semi-independent in children with ADHD-C, at least with regard to the
      elementary school age.

PMID- 18608646
TI  - A systematic review of psychological treatments for mild traumatic brain injury:
      an update on the evidence.
AB  - Mild traumatic brain injury (MTBI) is common and results in persisting disability
      for a minority of cases. Evidence guiding clinical management of this more
      complex group is lacking. This study systematically reviews
      psychological/neuropsychological treatments for adults with MTBI, with an
      emphasis on external validity. A total of 8 further studies were found adding to
      10 from previous reviews. Although the methodological quality remains poor, mild
      supportive evidence was found for educational interventions provided early
      following injury. However, the routine provision of interventions for all MTBI
      cases may not be effective. Continuing and novel research efforts are needed to
      identify factors associated with poor outcomes to enable efficient targeting of
      healthcare resources.

PMID- 18608647
TI  - Prediction of functional status in older adults: the ecological validity of four
      Delis-Kaplan Executive Function System tests.
AB  - This study tested the ecological validity of four Delis-Kaplan Executive Function
      System (D-KEFS) tests by examining how well performance on D-KEFS measures
      predicted observed daily functioning in community-dwelling older adults. Older
      adults ages 65 to 92 years completed four D-KEFS tests requiring planning and
      cognitive fluency. The four combined D-KEFS measures accounted for approximately
      26% of the variance in observed functional ability, when controlling for
      education and depression, thus supporting the ecological validity of the D-KEFS
      (Pearson r = .66). However, in a multiple regression analysis, the D-KEFS Trail
      Making Test-4 was the only measure of executive functioning that accounted for
      unique, independent variance in observed functional ability.

PMID- 18608648
TI  - Weak central coherence in eating disorders: a step towards looking for an
      endophenotype of eating disorders.
AB  - Previous work has found that women with anorexia nervosa and bulimia nervosa have
      weak coherence. The aim of this study was to examine whether women who had
      recovered from an eating disorder (ED) also had weak coherence. A total of 42
      recovered ED women and 42 healthy women were assessed with a battery of five
      neuropsychological tests that measure aspects of global or local functioning. The
      recovered ED group showed superior local processing and poorer global processing
      than the healthy group. These results are indicative of weak coherence. The
      finding that weak coherence is a stable characteristic rather than a state effect
      suggests that it may be an endophenotype for ED.

PMID- 18608649
TI  - Role of processing speed and premorbid IQ on visual recognition in patients with
      schizophrenia.
AB  - Previous research had shown that processing speed and premorbid IQ are predictors
      of verbal-memory efficiency in patients with schizophrenia. We investigated
      whether the same factors are involved in visual memory. A total of 49 patients
      with schizophrenia and 43 healthy controls were administered a picture
      recognition task. Half of the pictures were black and white, and half were in
      color, in order to vary the depth of encoding. Processing speed was measured by
      three standard tasks, and premorbid IQ was measured by the National Adult Reading
      Test (NART). Patients were significantly impaired in picture recognition.
      Regression analyses revealed that NART score was a significant predictor of the
      recognition of both types of picture in patients. Processing speed was a
      significant predictor of the recognition of the colored pictures. The effect of
      diagnosis on the recognition of colored pictures was reduced to nonsignificance
      when processing speed was entered in the regression. These data suggest that
      premorbid IQ is involved in visual-recognition efficiency. However, the deficit
      observed in patients is accounted for by decreased processing speed.

PMID- 18608651
TI  - Measuring neuropsychological change following breast cancer treatment: an
      analysis of statistical models.
AB  - This article considers the quantitative techniques currently in use in the
      evaluation of cognitive impairments associated with chemotherapy treatment for
      breast cancer. To illustrate differences among analytical approaches, all
      analyses were applied to baseline and posttreatment scores on neuropsychological
      tests obtained from Stages I and II breast cancer patients receiving either
      chemotherapy or hormonal therapy; a healthy control group with similar
      demographics to those of the treatment groups was also included. Conventional
      group analyses were compared with individual-based analyses (standardized
      regression-based and reliable change methods). Both univariate and multivariate
      techniques with and without covariates produced negligible effects. In contrast,
      results of the individual-based analyses identified a subset of participants in
      the chemotherapy group who experienced a severe decline in function on two or
      more tests. Differences between the control and treatment groups were greater
      than differences between the treatment groups alone. The standardized regression
      based approach was more sensitive than the reliable change index in detecting
      chemotherapy and hormonal therapy subjects whose performance was different from
      baseline scores on two or more tests (roughly 80% vs. 50% of participants). From
      a clinical perspective, the degree of impairment determined on the basis of the
      individual-based methodologies could have a major impact on quality of life for
      those affected. On the whole, we argue that the standardized regression-based
      approach, allowing for the assessment of individual practice effects and
      evaluation of moderator variables, is the method of choice in this context.

PMID- 18608652
TI  - Fitness to drive in multiple sclerosis: awareness of deficit moderates risk.
AB  - Fitness to drive was examined among 78 individuals with multiple sclerosis (MS)
      who participated with a knowledgeable informant. Illness severity,
      neuropsychological functioning, and external social influences each made unique
      contributions to the prediction of driving status. Among drivers, perceptions of
      social influences against driving accounted for the most variance in miles
      driven, whereas social influences, informants' perceptions of the patients'
      fitness to drive, and illness severity accounted for the most variance in adverse
      driving incidents. Importantly, awareness of deficit moderated fitness to drive:
      Drivers who were unaware of their deficits perceived less need to engage in
      compensatory behaviors; moreover, as perceived need to compensate decreased,
      miles driven and driving incidents increased. The findings have implications for
      interventions with persons with MS who drive.

PMID- 18608653
TI  - Subtypes of learning and memory on the California Verbal Learning Test-Second
      Edition (CVLT-II) in the standardization sample.
AB  - The purpose of this study was to determine representative, core profile subtypes
      of learning and memory, based on four variables representing different latent
      constructs, in the standardization sample of the California Verbal Learning Test
      Second Edition (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000). Two-stage cluster
      analysis identified six reliable subtypes. Variability in both level and pattern
      of performance contributed to the differentiation of these subtypes. Level of
      education was meaningfully related to variability in overall performance of the
      subtypes. Implications for the interpretation of CVLT-II findings obtained in
      clinical practice are discussed.

PMID- 18608655
TI  - Attention deficits of patients with chronic-stage traumatic brain injury: a
      behavioral study involving a dual visuo-spatial task.
AB  - We quantitatively evaluated memory performance in patients in the chronic stage
      of closed traumatic brain injury using dual visual tasks. Simple memory tests and
      questionnaires concerning activities of daily living (ADL) were also utilized to
      evaluate any correlation with the results of the dual tasks. The results of dual
      tasks and memory tests were correlated with the daily activity scores, but there
      was no correlation between the results of dual tasks and memory tests. We
      concluded that the dual task was effective for detecting memory and ADL
      disturbances, which were not disclosed by conventional memory tests.

PMID- 18608656
TI  - A screening test of English naming ability in bilingual Spanish/English speakers.
AB  - Difficulty with lexical retrieval (naming, in common parlance) is a frequent
      complaint in many neurological diseases, as well as in more benign conditions
      such as aging and fatigue. Accordingly, neuropsychological tests of picture
      naming are widely used in the assessment of conditions such as Alzheimer's
      disease, head injury, epilepsy, stroke, and multiple sclerosis. However, nearly
      all of these tests were created and standardized on samples of Caucasian,
      monolingual English speakers. Using a thorough set of selection criteria, the
      current study identified a set of picture stimuli that should be valid for
      screening visual naming defects in bilingual Spanish/English speakers. A total of
      51 pictures were identified, and data regarding important parameters of these
      stimuli (e.g., predominant response, types of responses) are provided. The
      results provide an important first step toward creating a valid
      neuropsychological screening test of English picture naming for Spanish/English
      bilingual speakers and have important clinical implications in light of the fact
      that this population is rapidly increasing in the United States.

PMID- 18608657
TI  - Neurocognitive vulnerability amongst university rugby players versus noncontact
      sport controls.
AB  - University rugby players were compared with IQ-equivalent noncontact sports
      controls on memory and attentional tasks at the pre- and postseason intervals.
      Results revealed significant lowering for rugby players relative to controls at
      the postseason interval for attentional tasks with a speeded visuomotor component
      (ImPACT Visual Motor Speed; Trail Making Test, TMT, A and B). There was a
      practice effect for controls only between the pre- and postseason intervals for
      attentional tasks that commonly reveal improvements after a long retest interval
      (TMT A and B; Digits Backwards). Medium to large effect sizes implicate
      clinically relevant cognitive vulnerability for university-level rugby players in
      association with years of exposure to repetitive concussive injury.

PMID- 18608658
TI  - Impulsive responding and the sustained attention   to response task.
AB  - Two studies investigated whether the sustained attention to response task (SART)
      is a better measure of impulsive responding than of sustained attention.
      Participants performed target detection tasks with global-local letter stimuli
      using one of two response formats: standard, responding to targets; and SART,
      withholding to targets. In the first experiment, performance in the SART changed
      rapidly over time, whereas performance in the standard format was stable over
      time. In the second experiment, performance in the SART was susceptible to global
      local condensation tasks, a result previously found with highly impulsive
      individuals. Overall the results indicate that the SART is sensitive to impulsive
      responding.

PMID- 18608660
TI  - The transience and nature of cognitive impairments in transient global amnesia: a
      meta-analysis.
AB  - Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden
      onset of severe amnesia without concomitant focal neurological symptoms. This
      meta-analysis of the cognitive characteristics of TGA addressed two main issues.
      First, we examined the hypothesis that the acute phase of TGA is associated with
      changes of anterograde and retrograde episodic long-term memory sparing semantic
      and short-term memory, while we had no clear prediction for potential reductions
      of executive functions due to the relative lack of previous studies addressing
      this issue. Second, we analyzed the time-course of changes in cognitive functions
      throughout three time intervals--acute (0-24 hours after TGA onset), postacute
      (24 hours to 5 days), and long-term phase (5-30 days)--to reveal whether there is
      a fast versus a delayed recovery. The results of the meta-analysis on 152 effect
      sizes from 25 studies showed that TGA is characterized by an extraordinarily
      large reduction of anterograde (d* = 1.89) and a somewhat milder reduction of
      retrograde (d* = 1.28) episodic long-term memory. Moreover, our results indicate
      the existence of additional, nonamnestic cognitive changes during TGA, because
      executive functions were also diminished (d* = 0.79). Reductions in both
      anterograde episodic long-term memory and executive function recover slowly, as
      slightly poorer performance in these cognitive domains can be found in the
      postacute phase (d*s = 0.32 and 0.44). All cognitive diminutions resolved within
      the long-term phase, by this calling into question previous reports of poorer
      performance of TGA patients relative to comparison subjects weeks or months after
      the attack.

PMID- 18608659
TI  - Successful life outcome and management of real-world memory demands despite
      profound anterograde amnesia.
AB  - We describe the case of Angie, a 50-year-old woman with profound amnesia (General
      Memory Index = 49, Full Scale IQ = 126) following a closed head injury in 1985.
      This case is unique in comparison to other cases reported in the literature in
      that, despite the severity of her amnesia, she has developed remarkable real
      world life abilities, shows impressive self-awareness and insight into the
      impairment and sparing of various functional memory abilities, and exhibits
      ongoing maturation of her identity and sense of self following amnesia. The case
      provides insights into the interaction of different memory and cognitive systems
      in handling real-world memory demands and has implications for rehabilitation and
      for successful life outcome after amnesia.

PMID- 18608661
TI  - Is neuropsychology a psychosocial science?
AB  - Many early investigators of brain-behavior relationships focused their
      investigative efforts on the psychiatric implications of brain damage and
      dysfunction. Descriptions of emotional dyscontrol and other psychosocial
      difficulties appeared frequently in their writings. Although dimensions of
      perception, memory, and cognition dominate the current neuropsychological
      literature, the psychosocial implications of patterns of neuropsychological
      assets and deficits retain their importance (e.g., in the study of the dementing
      diseases of adulthood). Our investigations of brain-behavior relationships and
      their impact on psychosocial functioning have attempted to expand upon and chart
      a somewhat different (subtypal) course for this area of study. One clearly
      evident conclusion of these efforts is that neuropsychology is a psychosocial
      science. Some implications of our findings for research and clinical practice are
      outlined.

PMID- 18608662
TI  - New measures to detect malingered neurocognitive deficit: applying reaction time
      and event-related potentials.
AB  - The ability of the Test of Memory Malingering (TOMM), reaction times (RTs), and
      event-related potentials (ERPs) to detect malingered neurocognitive deficit
      (MNCD) was examined in 32 normal individuals answering under honest (HON; n = 16)
      or malingering (MAL; n = 16) instructions as well as in 15 patients with
      traumatic brain injury (TBI) who answered under honest instructions. Overall, the
      TOMM was the most effective at classifying groups. However, new accuracy, RT, and
      ERP measures reached promising hit rates in the range of 71-88%. In particular,
      the difference in frontal versus posterior ERP obtained during an old-new task
      was effective at classifying MAL versus TBI (hit rate = 87%).

PMID- 18608664
TI  - Prospective memory in schizophrenia: the impact of varying retrospective-memory
      load.
AB  - The present study investigated event-based prospective memory in individuals with
      schizophrenia (n = 23) and healthy controls (n = 23). The retrospective-memory
      load was varied to disentangle the relative contributions of the retrospective
      and prospective components on prospective-memory functioning. A generalized
      prospective-memory deficit in schizophrenia emerged, with significant impairment
      evident even when retrospective-memory demands were minimal. Exploratory analyses
      suggest that both the retrospective and the prospective components contribute to
      the prospective-memory deficit in schizophrenia.

PMID- 18608665
TI  - Interplay between memory and executive functions in normal and pathological
      aging.
AB  - Healthy older adults and Alzheimer's disease (AD) patients are reported in the
      literature to be impaired in memory and executive functions. This research
      investigates the extent of these two abilities in determining pathological aging.
      Groups of young-old and old-old healthy people (Experiment 1) and individuals
      with amnestic mild cognitive impairment (a-MCI) and AD (Experiment 2) were
      administered verbal and visuo-spatial tests graded for memory and/or executive
      requirements. Results indicate a decline in visuo-spatial tasks requiring memory
      and executive functions in healthy aging. The a-MCI showed memory deficits
      similar to those shown by AD, but preserved executive functions. Executive
      function decline could be the critical feature of dementia.

PMID- 18608666
TI  - Cognitive deficits in essential tremor consistent with frontosubcortical
      dysfunction.
AB  - Essential tremor (ET) is increasingly thought to involve a heterogeneous group of
      patients, with some also exhibiting symptoms of Parkinson's disease (PD),
      including cognitive deficits. The goal of this study was to utilize a broad
      battery of neuropsychological measures to compare the cognitive function of 33 ET
      patients with that of 33 matched PD patients and 21 normal controls. Results
      indicated that the ET group performed significantly worse than controls across
      multiple cognitive domains, but performed remarkably similar to PD patients,
      consistent with frontosubcortical dysfunction.

PMID- 18608667
TI  - The primary cognitive deficit among males with fragile X-associated tremor/ataxia
      syndrome (FXTAS) is a dysexecutive syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative
      disorder associated with a premutation trinucleotide repeat expansion in the
      fragile X mental retardation 1 gene. Symptoms include gait ataxia, action tremor,
      and cognitive impairment. The objectives of the study were to clarify the nature
      of the dysexecutive syndrome observed in FXTAS and to assess the contribution of
      executive impairment to deficits in nonexecutive cognitive functions. Compared to
      controls, men with FXTAS demonstrated significant executive impairment, which was
      found to mediate group differences in most other cognitive abilities.
      Asymptomatic premutation carriers performed similarly to controls on all but two
      measures of executive functioning. These findings suggest that the impairment of
      nonexecutive cognitive skills in FXTAS is in large part secondary to executive
      dysfunction.

PMID- 18608669
TI  - Validity of the continuous visual memory test (CVMT) after traumatic brain
      injury.
AB  - The criterion validity of the Continuous Visual Memory Test (CVMT) was
      investigated using a sample of 53 patients with moderate-severe traumatic brain
      injury (TBI) and a demographically matched control group from the standardization
      sample. There was a statistically significant main effect of groups for both CVMT
      Total and Delayed Recognition scores ( p < .0001). Hierarchical linear regression
      analyses suggested that, in the clinical group, the effect of injury severity on
      the CVMT Total score was mediated by visuospatial ability. Logistic regression
      analyses revealed that the CVMT Total score correctly classified about three
      quarters of the combined participants, with slightly better specificity than
      sensitivity. It is concluded that the CVMT is a clinically useful instrument with
      satisfactory criterion validity but that it should not be used in isolation to
      determine the presence or absence of memory impairment.

PMID- 18608671
TI  - Exploring different routes of recovery from memory in Alzheimer's disease:
      evidence for preserved long-term priming.
AB  - Studies investigating implicit memory in Alzheimer's disease suggest that priming
      abilities disappear over time. This study investigates long-term priming in
      Alzheimer's disease. A total of 20 patients with Alzheimer's disease and 20
      controls underwent the Free and Cued Selective Reminding test. After a 30-minute
      delay, participants were submitted to a word identification task comprising the
      studied words and new words. The patients exhibited a long-term priming effect
      similar to that presented by the comparison group. Therefore, whereas explicit
      retrieval is definitely impaired in Alzheimer's disease, implicit processes
      allowing the retrieval of that same information operate relatively normally,
      including after a long delay.

PMID- 18608672
TI  - Information-processing speed is the primary deficit underlying the poor
      performance of multiple sclerosis patients in the Paced Auditory Serial Addition
      Test (PASAT).
AB  - The aims of this study were to determine which cognitive domains are evaluated by
      the Paced Auditory Serial Addition Test (PASAT) and to identify which of them are
      responsible for the poorer performance displayed by multiple sclerosis (MS)
      patients in this task. A total of 30 healthy controls and 30 MS patients
      completed the PASAT task as well as the different tests contained in the Brief
      Repeatable Battery of Neuropsychological Tests (BRB-N), some Wechsler Adult
      Intelligence Scale (WAIS-III) subtests, the Spanish version of the Chicago
      Multiscale Depression Inventory (CMDI), and a new PASAT-based task (ADD1) that
      was specifically designed for this study. Analysis of covariance and regression
      based analyses were performed to identify the predictors that are most strongly
      associated with the PASAT scores and the between-groups differences in the
      performance of this task. PASAT execution was associated with scores of the Digit
      Backward test, Symbol Digit Modality Test (SDMT), and measures of working memory
      and information-processing speed. On the other hand, differences between healthy
      volunteers and MS patients were mainly associated with the SDMT scores. MS
      patients also exhibited poorer execution than controls in the ADD1 task. Our
      results suggest that reduced information-processing speed (and not working
      memory) is the primary alteration underlying the lower scores in the PASAT task
      (and probably other cognitive deficits) that characterize MS patients. Based on
      these results, we suggest that tests that capitalize the role of information
      processing speed may be of special relevance in the neuropsychological assessment
      of this clinical population.

PMID- 18608673
TI  - Neuropsychological and symptom predictors of aggression on the psychiatric
      inpatient service.
AB  - Neuropsychological assessment of executive dysfunction may identify psychiatric
      patients who may be at high risk for aggressive behavior because impairment of
      the prefrontal cortex has been indicated as a possible anatomical correlate of
      aggression. No consensus, however, has been reached on the extent that executive
      dysfunction contributes to the formation of psychopathology and to aggressive
      behavior in psychiatric inpatients. We hypothesized a mediating model wherein
      patients' executive-functioning deficits contribute to the formation of
      psychopathological symptoms, which then underlies aggressive behavior. To test
      this model, we examined the relationship between executive functioning,
      psychiatric symptomatology, and aggressive behavior in 85 psychiatric inpatients
      presenting over an acute hospital admission using structure equation modeling
      techniques. The results revealed that psychiatric inpatients' executive function
      impairment significantly predicted the formation of psychiatric symptomatology,
      which in turn significantly contributed to the manifestation of aggressive
      behavior. Executive dysfunction also directly predicted inpatient aggressive
      behavior. Combining the indirect and direct effects, 59% of our inpatient
      aggression measure factor variance was accounted for by our measures of executive
      dysfunction and clinical symptom severity. These findings suggest that
      neurocognitive deficits underlie both psychiatric symptom formation and
      aggression. Patients with executive dysfunction may not possess the behavioral
      inhibition skills needed to cope with the presence of symptoms and other
      stressful events that accompany acute psychosis and hospitalization that may
      result, consequently, in increased manifestations of aggressive behavior.

PMID- 18608674
TI  - Self-assessment of driving ability and the decision to resume driving following
      stroke.
AB  - The decision to resume driving after stroke can be complicated by the sequelae of
      stroke as well as the established finding that even healthy adults overestimate
      their driving ability. This study evaluated whether stroke survivors (n = 67)
      disproportionately overestimated their driving ability as compared to healthy
      significant others (n = 67). Comparison to a known target reduced self-bias among
      both groups, but shift toward enhanced accuracy was significantly greater among
      survivors than significant others. Additionally, self-bias may reflect a
      pervasive trait of cognitive ability, as overestimation of driving ability was
      paralleled on a cognitive estimation task. Use of a specific criterion can
      facilitate accurate self-ratings of driving ability among survivors; however,
      actual decisions regarding driving status may be unrelated to self-view.

PMID- 18608675
TI  - Impaired inhibition of proactive interference in abstinent individuals with
      alcoholism.
AB  - Cognitive impairment has been associated with higher risk of alcoholism and
      relapse. Recent theoretical refinements have separated inhibition of dominant
      response and inhibition of proactive interference. We assessed the latter using a
      directed-forgetting procedure in 38 recently detoxified individuals with
      alcoholism and in 26 controls. On this task, memory performance of letter
      trigrams was compared when presented alone, followed by a second trigram to be
      recalled, then a second trigram to be forgotten (directed-forgetting condition).
      Individuals with alcoholism recalled more letters to be forgotten and performed
      worse than controls in the directed-forgetting condition, which significantly
      correlated with the duration of alcoholism.

PMID- 18608676
TI  - The clinical significance of neuropsychological changes following bilateral
      subthalamic nucleus deep brain stimulation for Parkinson's disease.
AB  - Despite the clinical importance of the question, a number of methodological
      issues have limited firm conclusions regarding the cognitive safety of deep brain
      stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD).
      Amongst these issues, studies have generally failed to consider the postoperative
      changes that occur within individual patients. This study utilized reliable
      change indices (RCIs) derived from a PD sample to determine the frequency of
      clinically significant postoperative decline on a battery of neuropsychological
      measures. This approach addresses measurement reliability, potential practice
      effects, and disease progression. The proportion of patients experiencing
      clinically significant postoperative decline on measures of list learning and
      verbal fluency was greater than expected based on disease progression; however,
      the majority of patients (55%) did not experience a significant decline in
      performance on any of the cognitive tests administered, and only one experienced
      decline on more than one test. Therefore, the statistically significant declines
      on measures of list learning and verbal fluency observed in the sample as a whole
      were the result of clinically significant declines experienced by a minority of
      participants.

PMID- 18608678
TI  - Age, family history, and memory and future risk for cognitive impairment.
AB  - PURPOSE: To provide a clinical tool for calculating a patient's future risk for
      developing cognitive impairment based on age, family history, and Rey Auditory
      Verbal Learning Test (AVLT) retention. PARTICIPANTS: 1,019 cognitively normal
      persons followed for an average of 5 years; 159 participants were eventually
      diagnosed with cognitive impairment. RESULTS: Risk of developing cognitive
      impairment increases with age and family history, but decreases with better
      memory performance. A nomogram is provided for calculation of relative risk of
      developing cognitive impairment in combinations of age, family history, and
      memory performance. CONCLUSIONS: These results enhance clinicians' ability to
      provide information to a patient about risk of cognitive impairment.

PMID- 18608677
TI  - Vascular and cognitive functions associated with cardiovascular disease in the
      elderly.
AB  - This study examines the relationship between systemic vascular function,
      neurocognitive performance, and structural brain abnormalities on magnetic
      resonance imaging (MRI) among geriatric outpatients with treated, stable
      cardiovascular disease and no history of neurological illness (n = 88, ages 56-85
      years). Vascular function was assessed by cardiac ejection fraction and output,
      sequential systolic and diastolic blood pressures, flow mediated brachial artery
      reactivity (BAR), and carotid intima media thickness (IMT). White matter
      hyperintensities (WMH) on MRI were quantified and examined relative to cognitive
      and vascular function. Principal component analysis revealed two primary vascular
      components: one associated with cardiac function, the other with atherosclerotic
      burden/endothelial dysfunction. Both factors were significantly associated with
      cognitive function and WMH volume. Reduced systolic variability and increased IMT
      were most strongly related to reduced attention, executive function, and
      information-processing speed. These findings suggest the possibility that
      systemic vascular indices may provide proxy measures of cerebrovascular
      dysfunction and reinforce the importance of achieving greater understanding of
      interaction between systemic vascular disease and brain dysfunction among elderly
      people with cardiovascular disease.

PMID- 18608679
TI  - Self-reported executive dysfunction, neuropsychological impairment, and
      functional outcomes in multiple sclerosis.
AB  - Although cognitive deficits are common in persons with multiple sclerosis (MS),
      the relationship between subjective complaints and objective impairment is
      sometimes obscured. To elaborate this issue, the present study examined the
      relationship between subjective complaints of dysexecutive syndrome,
      neuropsychological performance, and self-reported activities of daily living in
      42 people with MS and 13 control participants. Regression analyses revealed that
      subjective complaints of impairment, measured by the Frontal Systems Behavior
      Scale (FrSBe), emerged as a significant predictor of neuropsychological deficit
      and poor adaptive function. Accordingly, subjective complaints of dysexecutive
      function in MS may serve as a potent indicator of cognitive and functional
      impairment. Implications for research and clinical practice are discussed.

PMID- 18608680
TI  - Prospective-memory functioning is affected during pregnancy and postpartum.
AB  - Although there is considerable anecdotal and empirical evidence showing that
      retrospective memory may be adversely affected during pregnancy and postpartum,
      it remains unclear whether capacity for prospective memory is also impaired. In
      Phase 1 of the present study 20 participants in their third trimester of
      pregnancy were compared with 20 nonpregnant matched controls on a laboratory
      measure of prospective memory that closely represents the types of prospective
      memory tasks that actually occur in everyday life, in addition to a naturalistic
      time-logging prospective-memory task that was conducted over a period of 7 days
      as part of their day-to-day lives. In Phase 2, 15 of the pregnant women were
      retested on the time-logging task approximately 13 months after giving birth. The
      results indicated that although pregnancy was not associated with deficits on the
      laboratory measure of prospective memory, significant impairment was observed on
      the naturalistic measure. These preliminary data therefore provide the first
      empirical evidence showing that pregnancy may be associated with increased
      difficulty in implementing delayed intentions in everyday life.

PMID- 18608681
TI  - Mild cognitive impairment does entail retrograde amnesia for public events.
AB  - In this study memory for public events was evaluated in 15 amnesic mild cognitive
      impairment (aMCI) patients, whose clinical diagnosis was refined through a
      stringent selection procedure. A total of 9 patients were longitudinally
      reassessed over an 18-month period. About half of the participants were impaired
      at baseline and nearly 80% at the end of the 18-month follow-up. Moreover,
      retrograde memory declined significantly over time. Evidence of a pathological
      Ribot-type temporal gradient was found in about half of the aMCI patients. This
      is the first report of a remote memory deficit in aMCI. It highlights amnesia for
      public events as a frequent accompaniment of this condition. The findings tie in
      with the hypothesized role of the hippocampal complex in long-term memory.

PMID- 18608684
TI  - Measuring vocabulary by free expression and recognition tasks: Implications for
      assessing children, adolescents, and young adults.
AB  - Vocabulary tests are commonly used for assessing verbal ability. Most vocabulary
      tests employ the free expressive format that taps both verbal knowledge and
      expressive ability. The recognition format, which requires less expressive
      ability, has been suggested to be more sensitive in assessing the fund of verbal
      knowledge. We assessed vocabulary performance of 285 normal individuals (aged 6
      to 23 years) using both free expressive and recognition tasks. Results showed
      that participants aged 6 to 15 performed significantly better on the recognition
      than on the free expressive task. While the recognition task significantly
      correlated with the Test of Nonverbal Intelligence-Third Edition (TONI-III) IQ
      for individuals aged 9 and above, the free expressive task correlated with TONI
      III IQ only for young adults. Shortened 18-item versions yielded high reliability
      and correlation with the full version and reliable association with TONI-III IQ.
      These results highlight the utility of recognition tasks in measuring the fund of
      knowledge and suggest the possibility of developing shorter vocabulary tests for
      more cost-effective assessment.

PMID- 18608686
TI  - Evaluating the role of motor regulation in figural fluency: partialing variance
      in the Ruff Figural fluency test.
AB  - Figural fluency is often thought to assess the ability to "think fluently and
      flexibly in the visual-spatial mode" (Ruff, 1988). However, the contribution of
      motor regulation to the performance of this task has not been previously
      examined. The goal of this study was to evaluate the potential relationship
      between motor sequence fluency (without a visual-spatial component) and figural
      fluency. A total of 55 participants (ages 18 to 68 years) were administered (a)
      the Ruff Figural Fluency Task (RFFT), (b) the Trail Making Test Part B (TMT-B),
      which overlaps with the RFFT in visual tracking and graphomotor demands, (c) an
      electronically administered Motor Sequence Fluency Test (MSFT), which overlaps
      with the RFFT in generation of novel hand movements in the absence of visual
      stimuli, and (d) a Complex Motor Programming Task. Hierarchical regression
      analyses were used to determine whether complex motor programming uniquely
      contributes to RFFT performance above and beyond the processes that are
      traditionally assumed to be required, as well as to determine whether the ability
      to generate novel motor sequences uniquely contributes to RFFT performance. Age
      and education were also added to the regression models in order to determine the
      contribution of demographic variables to the current findings. Results indicated
      that age, specific components of motor programming, and nonvisual motor
      generative fluency represent the most prominent predictors of RFFT performance.
      Consequently, the role of motor regulation and motor flexibility may in fact be
      more important for RFFT performance than previously thought, whereas visual
      spatial processing may play a lesser role.

PMID- 18608687
TI  - Impairments in fine-motor coordination and speed of information processing
      predict declines in everyday functioning in hepatitis C infection.
AB  - Research increasingly supports the neurovirulence of chronic infection with the
      hepatitis C virus (HCV). For example, HCV infection has been associated with
      neuropsychological impairment in several ability areas, including psychomotor
      skills. This study aimed to examine whether HCV-associated neuropsychological
      impairment is predictive of declines in the independent performance of physical
      (PADLs) and instrumental (IADLs) activities of daily living. A total of 106
      volunteers with HCV infection completed a comprehensive neuropsychological,
      medical, and psychiatric research evaluation. As compared to 30 HCV-seronegative
      comparison participants, the HCV-infected group reported significantly greater
      declines in both PADLs and IADLs. Within the HCV cohort, individuals with
      impaired speed of information processing reported significantly greater IADL
      declines, whereas impaired fine-motor coordination was associated with declines
      in both IADLs and PADLs. In a series of regression analyses, impaired speed of
      information processing and depressive symptoms (as measured by the Beck
      Depression Inventory) were the only independent predictors of IADL declines,
      whereas general affective distress (as measured by the Profile of Mood States),
      sex, and fine-motor coordination impairment were predictive of declines in PADLs.
      Although the clinical assessment of HCV typically emphasizes both affective
      (e.g., depression) and physical factors, findings from the present study suggest
      that cognitive impairment is an important contributor to everyday functioning in
      persons living with HCV infection and therefore warrants consideration in
      clinical and research evaluations.

PMID- 18608690
TI  - Neuropsychological functioning following craniopharyngioma removal.
AB  - The neuropsychological functioning of patients who had undergone surgical removal
      of craniopharyngiomas was compared to that of an endocrine control group composed
      of patients with nontumor hypopituitarism, an obese control group, and a normal
      control group. Neuropsychological assessments consisting of measures of
      intelligence, memory, attention, and executive functioning were carried out. The
      craniopharyngioma group had lower Performance IQ than did the normal control
      group, but their Performance IQ was comparable to that of the hypopituitarism and
      obese control groups. The craniopharyngioma patients did not differ in Verbal or
      Full Scale IQs from the remaining groups. There were no group differences on
      measures of verbal or nonverbal memory, ability to sustain attention, or
      executive functioning including measures of verbal or figural fluency, nonverbal
      problem solving, ability to copy a complex geometric figure, and visual motor and
      visual sequencing skills. The group mean scores on the measures of intelligence
      and neuropsychological abilities for the craniopharyngioma patients were in the
      low-average to average range. While craniopharyngioma patients can have
      significant morbidity including endocrine and visual deficits as well as obesity
      resulting from hyperphagia, neuropsychological deficits are not always present.
      Their neuropsychological outcome is more benign than some previous studies have
      suggested.

PMID- 18608691
TI  - Presentation modality influences WAIS Digit Span performance in younger and older
      adults.
AB  - The WAIS-R Digit Span subtests require oral presentation of digits. Older adults
      with hearing impairments may have reduced recall due to deficits in hearing. It
      is also possible that older adults' recall is influenced by recall superiority
      for auditory versus visual information (the auditory superiority effect).
      Auditory and visual versions of the Digits Forward and Backward tasks were
      administered to 30 younger adults (18-30 years) and 30 older adults (65-78
      years). Although younger adults exhibited marginally better digit recall overall
      than older adults, all participants' scores were highest for the auditory
      presentation mode.

PMID- 18608689
TI  - Variable patterns of neuropsychological performance in HIV-1 infection.
AB  - Based upon prior findings with group means, a "prototypical pattern" of
      neuropsychological results with HIV infection has emerged: impaired executive
      functioning, motor skills, speed of information processing, and learning, with
      intact memory retention, most language skills, and visuospatial functioning. We
      examined neuropsychological results from 553 HIV+ adults to determine the number
      of patterns seen among individuals with HIV infection. Factor analysis of a
      relatively comprehensive neuropsychological battery identified 6 component
      factors: verbal memory (VeM), visual memory (ViM), processing speed (PS),
      attention/working memory (A/WM), executive function (EF), and motor (M). These
      factor scores were submitted to hierarchical cluster analysis, to determine the
      appropriate number of clusters or patterns in the cohort. Final cluster
      membership was then determined by K-means analysis, based on the Lange, Iverson,
      Senior, and Chelune (2002) method. A 6-cluster solution was found to be most
      appropriate. The definitions of the clusters were based upon ipsative scoring of
      factor scores to indicate relative strengths and weaknesses (independent of
      overall level of performance): Cluster 1: strong EF; Cluster 2: strong M, weak
      VeM and EF; Cluster 3: strong PS, weak ViM and EF; Cluster 4: strong VeM, weak M;
      Cluster 5: strong A/WM; Cluster 6: strong VeM, weak EF. Neuropsychological
      impairment rates differed across clusters, but all 6 clusters contained
      substantial numbers of impaired and unimpaired individuals. Cluster membership
      was not explained by demographic variables or psychiatric or neuromedical
      confounds. Thus, there does not appear to be a single, prototypical pattern of
      neuropsychological impairment associated with HIV infection for this battery of
      representative neuropsychological tests.

PMID- 18608692
TI  - Effects of level of processing at encoding and types of retrieval task in mild
      cognitive impairment and normal aging.
AB  - A total of 16 young (M = 27.25 years), 13 healthy elderly (M = 75.38 years), and
      10 older adults with probable mild cognitive impairment (MCI; M = 78.6 years)
      carried out a task under two different encoding conditions (shallow vs. semantic)
      and two retrieval conditions (free recall vs. recognition). For the shallow
      condition, participants had to decide whether the first or last letter of each
      word in a list was "E." For the semantic condition, they had to decide whether
      each word represented a concrete or abstract entity. The MCI group was only able
      to benefit from semantic encoding to the same extent as the healthy older adults
      in the recognition task, whereas the younger and healthy older adults benefited
      in both retrieval tasks. These results suggest that the MCI group required
      cognitive support at retrieval to make effective use of semantic processing
      carried out at encoding. In the discussion, we suggest that adults with MCI
      engage more in deep processing, using the semantic network, than hitherto
      thought.

PMID- 18608693
TI  - An exploratory study of long-term neurocognitive outcomes following recovery from
      opportunistic brain infections in HIV+ adults.
AB  - Central nervous system opportunistic infections (CNS-OI) are a significant cause
      of morbidity and mortality in AIDS. While current interventions are increasingly
      successful in treating CNS-OI, little information exists regarding long-term
      behavioral outcomes among survivors. In this exploratory study we examined
      neurocognitive data among three groups of adults with different AIDS-related CNS
      OI: 15 with past cryptococcal meningitis (CM), 8 with toxoplasmosis encephalitis
      (TE), and 8 with progressive multifocal leukoencephalopathy (PML). A group of 61
      individuals with AIDS, but without CNS-OI, was used as a comparison group. A
      battery of standardized neuropsychological tests assessing a variety of cognitive
      domains was administered upon entry. Results indicate that individuals with a
      history of CNS-OI were most impaired on measures of cognitive and psychomotor
      speed relative to the HIV+ comparison group. Among the CNS-OI groups, individuals
      with history of TE had the most severe and varied deficits. The results are
      discussed in relation to what is known about the neuropathological consequences
      of the various CNS-OIs. While this is the first systematic group study of
      residual CNS-OI effects on neurocognitive function, future studies employing more
      participants, perhaps focusing on specific CNS-OIs, will further characterize the
      long-term outcomes in AIDS-related CNS-OI.

PMID- 18608695
TI  - Perceived conflicts and errors in complex problem solving.
AB  - In a behavioral experiment on 60 healthy volunteers, the Tower of London was
      employed as a complex visuo-spatial planning task. After each trial, participants
      were asked how difficult they found the task and whether they thought their
      solution was optimal. Results showed that objective problem difficulty affected
      behavioral performance as well as subjectively experienced difficulty and
      performance certainty. This pattern was influenced by experimental manipulation
      of participants' knowledge of objective problem difficulty: For optimally solved
      problems, performance certainty remained at high levels if such knowledge was
      provided, and strongly declined in more difficult problems if it was withheld.
      For nonoptimally solved problems, subjects' ratings indicated awareness of errors
      when they were informed about objective problem difficulty; otherwise,
      performance certainty declined from intermediate to low levels in more difficult
      problems. No such interaction was observed with regard to ratings of subjective
      problem difficulty. Additional structural equation modeling revealed that
      subjective awareness of errors and processing conflicts can be considered as
      independent only for optimally solved trials in which the optimal solution was
      known to the participants. We conclude that participants' ratings of problem
      difficulty and performance certainty can be regarded as indicators of at least
      partly distinct processes of performance monitoring, and that studies of complex
      problem solving incorporating such subjective measures may enhance the empirical
      basis of current theories of executive functioning.

PMID- 18608694
TI  - Cognitive mechanisms of switching in HIV-associated category fluency deficits.
AB  - HIV infection is associated with deficits in category fluency, but the underlying
      cognitive mechanisms of such impairments have not been determined. Considering
      the preferential disruption of the structure and function of frontostriatal
      circuits in HIV disease, the present study evaluated the hypothesis that HIV
      associated category fluency deficits are driven by impaired switching. Study
      participants were 96 HIV-infected individuals and 43 demographically comparable
      healthy comparison volunteers who were administered a standard measure of animal
      fluency and an alternating category fluency task (i.e., fruits and furniture) in
      a randomized order. Consistent with prior research on letter fluency, HIV
      infection was associated with greater impairments in switching, but not semantic
      clustering within the animal fluency task. Moreover, a significant interaction
      was observed whereby the HIV-associated deficits in switching were exacerbated by
      the explicit demands of the alternating fluency task. Across both fluency tasks,
      switching demonstrated generally small correlations with standard clinical
      measures of executive functions, working memory, and semantic memory.
      Collectively, these findings suggest that HIV-associated category fluency
      deficits are driven by switching impairments and related cognitive abilities
      (e.g., mental flexibility), perhaps reflecting underlying neuropathology within
      prefrontostriatal networks.

PMID- 18608696
TI  - The contribution of anterior and posterior regions of the right hemisphere to the
      recognition of emotional faces.
AB  - To investigate the contribution of posterior and anterior parts of the right
      hemisphere (RH) to emotional facial recognition, we studied 11 participants with
      anterior strokes of the right hemisphere (ASRH), 16 patients with posterior
      strokes of the right hemisphere (PSRH), and 31 normal controls. All individuals
      were right-handed and nondemented. The ability to recognize emotional facial
      expressions was assessed by using Ekman and Friesen's (1976) Pictures of Facial
      Affect. Analysis revealed that both groups of patients presented with an impaired
      recognition of emotional faces. However, patients with PSRH were able to identify
      facial expressions better than participants with ASRH. In comparison to
      participants sustaining PSRH, patients with ASRH were particularly impaired on
      recognizing faces of negative valence. Thus, our results suggest that anterior
      parts of the RH seem to play an important role in the recognition of emotional
      facial expressions.

PMID- 18608697
TI  - Inhibition and attention in adolescents with nonmanic mood disorders and a high
      risk for developing mania.
AB  - This study examines psychomotor inhibition, sustained attention, and inhibitory
      attentional control in adolescents (ages 12-18 years) with a nonmanic mood
      disorder and with a first-degree relative with bipolar I disorder (MD, N = 20)
      and demographically matched healthy children of parents without any psychiatric
      disorder (HC, N = 13). MD participants showed abnormal performance in stop signal
      reaction time and latency (d = 1.28 and 1.64, respectively), sustained attention
      response bias (d = 0.75), and color naming speed (d = 0.88). The results indicate
      that MD participants exhibit psychomotor disinhibition, marginal cognitive
      slowing and cautious response biases, but no formal deficits in sustained or
      selective attention.

PMID- 18608698
TI  - Cognitive functioning predicts survival in the elderly.
AB  - Prior studies of aging have identified a number of predictors of survival,
      including performances on some cognitive-functioning tests. However, few studies
      have used a multidomain test battery to identify which specific cognitive
      abilities predict death. The current study examined the 12 subtests of the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to see
      which subtests predicted death in a sample of 796 older, primary care patients.
      After 4 years, 98 individuals died, and 698 individuals remained alive. The
      individuals who died performed more poorly at baseline on 9 of the 12 RBANS
      subtests (p < .05) than did their peers who remained alive. In a multivariate
      analysis, however, only the RBANS Coding subtest independently predicted death (p
      < .001), along with male gender and greater initial medical comorbidity. Although
      the mechanism of poorer cognition and impending death remains unclear, some
      possibilities are discussed (e.g., brain dysfunction, poor medical compliance,
      impaired cellular immunity).

PMID- 18608701
TI  - Impaired stimulus-outcome but preserved stimulus-response shifting in young
      substance-dependent individuals.
AB  - Substance dependency has been related to an impairment in executive functions and
      to a dysfunction of the frontal cortex. In this study we developed two
      experimental tasks, which are physically identical, to analyze whether substance
      dependent individuals are impaired in shifting response patterns (stimulus
      response links) or preferences (stimulus outcome links). To increase the
      specificity of the dependent variable, we also used two control tasks to analyze
      for unspecific performance deficits. We included 35 young subjects with
      polysubstance abuse (International Classification of Diseases, F19.2 ICD 10
      diagnosis, mean age of 22 years, maximum age < 27 years) and 18 normal controls,
      but for a first step focused on only 22 patients and 15 age-matched controls,
      because we excluded all patients with an IQ below 100. The results show that the
      substance-dependent individuals are selectively impaired in shifting object
      preference (stimulus-outcome links) and not in shifting response patterns. They
      moreover show a higher general impulsivity as reflected in their faster responses
      than controls on all tasks except the stimulus-outcome task. In a second step we
      replicated these results by analyzing the original groups of 35 patients and 18
      controls. We argue that substance-dependent subjects show an impairment only on
      specific executive tasks, and these tasks concern stimulus-outcome link shifting,
      which has been associated with the functioning of the orbitofrontal cortex, not
      of the lateral prefrontal cortex.

PMID- 18608702
TI  - The dual treatment of acne vulgaris using two kinds of ELOS (electro optical
      synergy) system: a simultaneous split-face trial.
AB  - BACKGROUND: RF-pulsed light with ELOS technology devices have recently been used
      to treat acne vulgaris in selected patients. OBJECTIVE: To investigate the safety
      and efficacy of a combination of two kinds of device with ELOS technology for the
      treatment of acne. METHODS: Ten patients with moderate acne were treated twice
      weekly for 4 weeks with the Aurora AC (Syneron Medical Ltd, Yokneam, Israel), a
      combination of pulsed light and RF energy. Immediately after Aurora AC treatment,
      all patients were treated weekly only on one facial half with the Matrix IR
      (Syneron Medical Ltd), a combination of fractional diode laser and RF energy.
      Photographic documentations were obtained at baseline, before each treatment
      session, and 1 and 3 months after the final treatment. RESULTS: At 3 months after
      treatment, the mean lesion count was reduced by 38% (p<0.05) after eight
      treatments with the Aurora AC alone. With additional treatment with the Matrix
      IR, the mean lesion count was reduced by 61%. CONCLUSION: The combination of
      Aurora AC and Matrix IR was superior in reducing the acne lesion count, and in
      extending the length of the remission period.

PMID- 18608703
TI  - Clinical trial of a pinpoint irradiation technique with the CO2 laser for the
      treatment of atrophic acne scars.
AB  - Ablative laser resurfacing is an effective treatment for atrophic acne scars.
      However, it often induces complications such as edema, prolonged erythema,
      scarring and hyperpigmentation. Therefore, a new concept of laser treatment
      called fractional photothermolysis has been designed to create microscopic
      thermal wounds to achieve skin rejuvenation treatment of atrophic acne scars.
      This study was designed to prospectively evaluate the use of a technique similar
      to fractional photothermolysis using only the standard CO2 laser without the
      fractional laser device in the treatment of atrophic scars and demonstrates it as
      a safe, effective and economical treatment option. Clinical improvement was
      achieved in all 35 patients with minimal adverse effects.

PMID- 18608704
TI  - Hair transplantation for men.
AB  - Men throughout history have suffered from various degrees of hair loss. Modern
      techniques for hair transplantation give rise to natural and long-lasting
      results. In this paper we provide an overview of the procedure, including the
      harvesting of donor hair in the occipital scalp, and its redistribution along the
      frontal- and mid-scalp areas. Special consideration must be made to choosing the
      candidates carefully and to performing their surgery in a manner that looks
      appropriate for all ages. We describe the role of medications for male pattern
      hair loss and with hair transplantation.

PMID- 18608705
TI  - Safe and effective treatment of problem scars with the purely thermal non
      ablative Er:YAG laser scar mode.
AB  - INTRODUCTION: Traumatic events as well as surgery can cause a large variety of
      scars, which are often a major psychological concern to patients. Moreover,
      patients often report itching or burning sensations as well as pain. We
      investigated the efficacy of purely non-ablative laser therapy in order to
      improve the appearance and quality of these scars. METHODS: A total of 62
      patients with problem scars were enrolled in the study. The purely thermal, non
      ablative scar mode of an Er:YAG laser (BURANE XL; Wavelight AG, Erlangen,
      Germany) was used. One to six treatment sessions were performed. The improvement
      of scar redness, scar flatness, scar quality, itching and burning sensations as
      well as pain and patient satisfaction were evaluated. RESULTS: The overall scar
      quality improved in 93% of patients. Similarly, the flatness improved in 89% of
      scars, itching sensation in 79% and burning sensation in 86% of patients. In 91%
      of scars a decrease of scar redness was seen and all painful scars showed a pain
      reduction. Average patient satisfaction was 7.4 on a 10-point scale. Sixty-one
      patients would recommend the therapy to another person. Side effects were limited
      to transient erythema and oedema. CONCLUSION: The high success rate combined with
      the low side-effects resulted in high patient satisfaction. Post-traumatic or
      post-surgical scars can safely and effectively be treated by the thermal scar
      mode of the Er:YAG laser used.

PMID- 18608706
TI  - Confusion about diffusion and the art of misinterpreting data when comparing
      different botulinum toxins used in aesthetic applications.

PMID- 18608707
TI  - Facial scars after a road accident: combined treatment with PDL and Q-switched
      ND:YAG laser.
AB  - We report the case of a woman who presented with several facial scars following a
      road accident. Treatment was carried out using combined laser treatment with
      pulsed dye laser (PDL) and the Q-switched neodymium:yttrium-aluminum-garnet laser
      (QS Nd:YAG laser). No side effects or complications from treatment were noted or
      reported. The patient had very good cosmetic results with this combined
      technique. A variety of facial scars--erythematous, pigmented, atrophic and
      hypertrophic--may occur as a result of trauma, surgery, burns and skin disease.
      Surgery with other adjunctive methods including radiotherapy, intralesional
      steroids and pressure therapy has shown variable results. Laser treatment has
      been attempted for scar revision since the 1980s. The PDL is the optimal
      treatment for reducing scar bulk and symptoms. It also decreases the erythema and
      telangiectasia associated with scars, normalizes the skin surface texture and
      improves scar pliability. The QS Nd:YAG laser (1064 nm) is highly effective for
      traumatic tattoo removal, resulting in complete clearance in the majority of
      cases.

PMID- 18608708
TI  - Validation of clinical and image skin scoring systems for a single chronic
      discoid lupus erythematosus lesion.
AB  - OBJECTIVE: The purpose of this study was to achieve a validated clinical and
      image scoring system for a single chronic discoid lupus erythematosus (CDLE)
      lesion. METHODS: Fifteen patients with a CDLE lesion were scored twice by four
      observers and clinical photographs were taken. These pictures were assessed by
      the same four observers at two time points. Patients were scored using the DLE
      Skin Score (DLE-SS). In addition, the DLE-Photo Score (DLE-PS) was calculated.
      Statistical analysis was carried out by measuring inter- and intra-observer
      agreement for both methods and by measuring the correlation between the DLE-SS
      and DLE-PS. RESULTS: Both the DLE-SS and DLE-PS proved reliable methods in the
      assessment of CDLE. The inter-observer variability of the DLE-SS and DLE-SS was
      low. The intra-observer variability was estimated to be 0 in both methods. The
      correlation coefficient between the DLE-SS and DLE-PS was high (0.81).
      CONCLUSION: Both the DLE-SS and the DLE-PS are reliable and easy-to-use methods
      to score disease activity in CDLE patients, and can be used in monitoring single
      target lesions in clinical trials.

PMID- 18608709
TI  - In vitro antibacterial effects of topical local anesthetics.
AB  - BACKGROUND: The antibacterial activities of local anesthetics are recognized.
      OBJECTIVE: To investigate in vitro the activity of topical local anesthetic
      ointments at clinical doses. METHODS: The activity of two different local
      anesthetic ointments including lidocaine 5% and lidocaine/prilocaine 2.5% was
      tested against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia
      coli, Pseudomonas aeruginosa, Streptococcus pyogenes and Enterococcus faecalis by
      the disc-diffusion method. Sterile discs containing topical local anesthetic
      drugs were prepared taking into account the doses of ointments used in clinical
      practice. The validity of the methodology was confirmed using topical
      antibacterial mupirocin. The inhibition zones of the discs were measured.
      RESULTS: Mupirocin inhibited all the bacteria. Both local anesthetic ointments
      were found to be most effective on E. coli, whereas they had no effects on P.
      aeruginosa. Lidocaine 5% revealed antibacterial activity against S. aureus, S.
      epidermidis, E. coli, S. pyogenes and E. faecalis, but lidocaine/prilocaine 2.5%
      showed no activity on E. faecalis and inhibited S. pyogenes only at double doses.
      It was also observed that the antibacterial activity was in a dose-dependent
      manner. CONCLUSION: In the light of these findings, it might be concluded that
      topical local anesthetic ointments in routine settings may have a preventive role
      against some bacteria.

PMID- 18608710
TI  - Red scrotum syndrome: successful treatment with oral doxycycline.
AB  - BACKGROUND: Red scrotum syndrome often follows the prolonged application of
      topical corticosteroids to the scrotal area and is characterized by persistent
      erythema of the scrotum associated with severe itching, hyperalgesia, and a
      burning sensation. Several topical and systemic treatments have been used in the
      past without success. OBJECTIVE: To assess the efficacy of oral doxycycline, in
      addition to corticosteroid abstinence, in the treatment of red scrotum syndrome.
      METHODS: In a retrospective chart review, seven patients with red scrotum
      syndrome, who presented between 2004 and 2007 to the outpatient clinic at the
      American University of Beirut Medical Center, were identified as having been
      treated with oral doxycycline and steroid abstinence. RESULTS: All patients
      reported significant improvement (between 50%and 80%) of their symptoms within 2
      weeks of starting doxycycline and had marked improvement of the erythema and
      complete resolution of symptoms in a period ranging from 2 to 3 months.
      CONCLUSION: We suggest that doxycycline may be effective in the treatment of red
      scrotum syndrome.

PMID- 18608711
TI  - Triggering of pityriasis lichenoides et varioliformis acuta by radiocontrast
      iodide.
AB  - OBJECTIVE: Pityriasis lichenoides et varioliformis acuta (PLEVA) is characterized
      by 2-3 mm erythematous papules that became vesiculopustular with hemorrhagic
      necrosis. METHOD & MATERIAL: A 45-year-old lady, a known case of parathyroid
      adenoma, presented with a generalized itchy skin rash starting four days after
      radiocontrast iodide injection. RESULT: There are some reports of provocation of
      PLEVA by tegafur and astemizole. CONCLUSION: We report for the first time the
      triggering of PLEVA by radiocontrast iodide injection.

PMID- 18608712
TI  - Plasma homocysteine level is elevated in patients on isotretinoin therapy for
      cystic acne: a prospective controlled study.
AB  - PURPOSE: Isotretinoin (Iso) has marked side effects. Homocysteine (Hcy)
      metabolizes in the liver, requiring folate and vitamin B12. Elevated blood levels
      of Hcy have been linked to an increased risk of premature coronary artery disease
      (CAD). In this study, we evaluated Hcy levels, vitamin B12, and folate in
      patients on Iso treatment for cystic acne (CA). METHODS: Seventy-four patients
      with CA were included to the study group. Blood levels of Hcy, vitamin B12, and
      folate were assessed before and after 45 days of Iso therapy. The control group
      consisting of 80 individuals were tested once. RESULTS: Hcy levels were
      statistically significantly increased in patients on Iso treatment. Vitamins were
      unaltered, while lipids and liver enzymes increased statistically significantly.
      CONCLUSION: Hcy levels are elevated in patients on Iso treatment for CA. It may
      be due to either the inhibition of cystathionine-beta-synthase, an enzyme
      required in the metabolism of Hcy, by the drug and/or the liver dysfunction.
      Daily supplementation with vitamin B12 and folate, which are the cofactors of the
      enzymatic reactions involved in Hcy metabolism, can lower plasma levels of Hcy,
      so it is recommended to take these vitamins in case of deficiency along with Iso
      to prevent premature occlusive vascular disease.

PMID- 18608713
TI  - Acitretin is a safe treatment option for infantile pustular psoriasis.
AB  - Generalized pustular psoriasis (GPP) is a rare type of psoriasis and is
      considered the most severe variant. Infantile pustular psoriasis (IPP) is a very
      rare form of GPP. Severe IPP may be difficult to control and is complicated by
      bacterial superinfection, dehydration, and sepsis. Herein, a 2.5-month-old infant
      with IPP is presented, who was successfully treated with systemic retinoid
      therapy, which appears to be a safe and effective option for this challenging
      pustular eruption of childhood.

PMID- 18608715
TI  - Clinical investigation of acitretin in children with severe inherited
      keratinization disorders in China.
AB  - OBJECTIVE: Investigation into the clinical efficacy, side effects and safety of
      oral acitretin on severe inherited disorders of keratinization in children.
      METHODS: Acitretin was given as a treatment dose of 0.77-1.07 mg/kg x per day
      (mean 0.86+/-0.11) and maintenance dose of 0-0.94 mg/kg x per day (mean 0.33+/
      0.26) to 28 children with severe inherited disorders of keratinization. Body
      height and weight were chosen as the monitoring indexes to evaluate the growth
      and development and other common side effects as the safety evaluation of the
      children for a follow-up of 2-36 months. RESULTS: After 2-4 months of treatment,
      the clinical cure rate was 82.1% and the effective rate was 17.9%. Most cases,
      such as bullous ichthyosiform erythroderma, lamellar ichthyosis, pityriasis rubra
      pilaris, and inflammatory linear verrucous epidermal nevus showed remarkable
      therapeutic response; non-bullous ichthyosiform erythroderma was also effective.
      Two cases with Darier's disease were previously shown to be resistant to
      acitretin therapy, but improved after 6 months of treatment. No previous
      investigation had been made on a negative effect on the growth and development of
      such children. CONCLUSION: Acitretin showed a satisfactory therapeutic effect on
      severe inherited disorders of keratinization in children.

PMID- 18608717
TI  - Successful treatment of perforating granuloma annulare with 0.1% tacrolimus
      ointment.
AB  - Perforating granuloma annulare (PGA) is a rare subtype of granuloma annulare (GA)
      named in 1971 by Owens and Freeman. It is characterized by necrobiotic areas
      surrounded by histiocytes and lymphocytes with transepidermal elimination. Many
      treatments for PGA have been used, often with unsatisfactory results. Tacrolimus
      in its topical formulation has been established as a safe and effective
      alternative to topical corticosteroids because of its mild side effects and its
      minimal systemic absorption. Topical tacrolimus has been approved for the
      treatment of atopic dermatitis; moreover, ample data exist which demonstrate the
      usefulness of tacrolimus for the specific treatment of other inflammatory
      diseases. We report a 70-year-old diabetic woman with PGA, in whom the ulceration
      due to PGA responded to 0.1% topical tacrolimus.

PMID- 18608718
TI  - Perineal muco-cutaneous herpes zoster treated with brivudin.
AB  - Herpes zoster results from the reactivation of latent varicella-zoster virus
      (VZV) from the dorsal root ganglion of sensory nerves. It is rarely described in
      the pediatric population. We report the case of an 8-year-old immunocompetent boy
      with a painful lumbosacral herpes zoster that was treated with brivudin and
      achieved rapid and sustained improvement in the absence of muco-cutaneous or
      pharmacological side effects.

PMID- 18608725
TI  - Patients' views on care and treatment after phototherapy for psoriasis and atopic
      eczema including a gender perspective.
AB  - BACKGROUND: Psoriasis and atopic eczema are reportedly as common among women as
      among men and are not known to differ in severity between sexes. Research has
      shown that men get more treatment with ultraviolet (UV) light for longer periods
      than women. This fact, together with ongoing efforts to improve patient
      satisfaction with care and treatment at our department, prompted us to gather
      information from our patients. OBJECTIVE: The aim of this study was to explore
      patients' views of dermatological care and treatment methods. METHOD: A
      questionnaire-based survey was carried out, complemented with qualitative
      interviews. RESULTS: The main findings fall under three areas of clinical
      relevance: information to patients must be individually designed with a gender
      perspective; men and women have different attitudes towards greasing which must
      be kept in mind in clinical practice; and women often appear to be under
      prescribed UV treatment. CONCLUSION: The information from our study can form a
      basis for new therapeutic strategies, taking a gender perspective into account.

PMID- 18608726
TI  - Long-term course and treatment of a cutaneous BCG infection.
AB  - The authors report and discuss a rare case of the long-term course and treatment
      of cutaneous BCG infection in an HIV-negative, healthy nurse. Over 5 years we
      cured the wrist and lower leg cutaneous tuberculosis infection caused by an
      accident at work. Persistent antituberculous therapy and surgical procedure were
      applied, but after detection of an encapsulated abscess in the wrist followed by
      needle aspiration, antituberculous therapy was sufficient and our patient was
      cured. Failing the addition of local applications, antituberculous therapy with
      radical surgical treatment remains the recommended treatment in cutaneous
      infections.

PMID- 18608727
TI  - Combination therapy of cyclosporine and methylprednisolone on severe alopecia
      areata.
AB  - BACKGROUND: Although systemic cyclosporine appears to be one of the treatment
      options for chronic severe alopecia areata (AA), the high recurrence rates after
      discontinuation and side effects make cyclosporine a nominal agent for the
      treatment of AA. OBJECTIVE: This study was designed to determine whether the
      combination therapy of cyclosporine and methylprednisolone could be an effective
      treatment for severe AA. METHODS: A total of 46 patients with severe AA were
      treated with a combination of cyclosporine (200 mg twice daily, two 100 mg
      tablets) and methylprednisolone (24 mg twice daily for men, 20 mg twice daily for
      women, and 12 mg twice daily for children). The doses of methylprednisolone were
      diminished by 4 mg/day weekly, and the dose of cyclosporine was decreased
      gradually after cessation of administration of methylprednisolone. RESULTS: Three
      (6.5%) of 46 patients discontinued the treatment due to side effects. Of the
      remaining 43 patients, 38 (88.4%) had significant hair regrowth and five (11.6%)
      were considered to be treatment failures. Nine (23.7%) relapsed during the
      observation period of 12 months. CONCLUSIONS: Although limited by its
      uncontrolled character, this study shows that combination therapy with
      cyclosporine and methylprednisolone may be a useful treatment for severe AA.

PMID- 18608728
TI  - Cutaneous alternariosis in a kidney transplantation recipient: report of a case.
AB  - Phaeohyphomycoses are induced by dematiaceous or darkly pigmented fungi.
      Alternaria species are the most important causative agents. Factors such as
      immunosuppression, local wounds or systemic disease are generally present. We
      report a case of phaeohyphomycosis induced by Alternaria alternata in an
      immunocompromised patient. The main interest in this case is the rareness of the
      cutaneous alternariosis and of its clinical aspects and the good response to
      therapy. Recognition of Alternaria spp. as potential opportunistic pathogens is
      important for the differential diagnosis of dermatological lesions, such as
      granulomatous or ulcerative lesions in immunocompromised patients.

PMID- 18608730
TI  - Clinical considerations on the use of concomitant therapy in the treatment of
      acne.
AB  - Acne is a disease that affects millions of people worldwide and requires prompt
      and effective management of both the physical and psychological sequelae that an
      individual may experience. The ultimate goal of treatment is to address as many
      of the pathogenic factors of acne as possible while minimizing side effects.
      Numerous therapeutic options are available; however, most current treatment
      options address only one or two of these factors. For this reason, combining
      single therapies has been the practice since the mid-1970s, beginning with the
      concomitant use of treatments such as topical vitamin A with systemic
      tetracyclines or topical benzoyl peroxide. As additional therapeutic options have
      emerged, dermatologists have also begun to utilize these treatments concomitantly
      based on their synergistic and multifactorial effects on the different pathogenic
      factors of acne. This review provides an update of recent advances and data
      regarding the concomitant use of various anti-acne agents.

PMID- 18608731
TI  - Infliximab-induced acne: a new case and review of published reports.

PMID- 18608733
TI  - Experience with photodynamic therapy in Hailey-Hailey disease.
AB  - Hailey-Hailey disease (HHD) is a rare genodermatosis that is often difficult to
      treat. This paper reports three patients with HHD treated with one session of
      photodynamic therapy (PDT) using topical methyl aminolevulinic acid applied under
      occlusion for 3 hours and red light at 37 J/cm2 for 7.5 minutes. Our results are
      not successful: all of the patients suffered discomfort during the 3-4 weeks
      following PDT and only one patient experienced clinical improvement. None of the
      patients would like to repeat the treatment. PDT is at an exploratory stage;
      further studies are necessary to determine whether PDT is useful in the treatment
      of HHD.

PMID- 18608734
TI  - 'Coral reef' psoriasis: a marker of resistance to topical treatment.
AB  - Psoriasis plaques that have very thick adherent scale (so-called coral reef or
      rupioid psoriasis) tend to be resistant to topical treatment. We present a case
      of coral reef psoriasis that responded to topical clobetasol 0.05% spray without
      concomitant use of moisturizers or keratolytic agents. We propose that coral reef
      psoriasis is resistant to topical corticosteroids because of poor adherence to
      treatment, not because of poor penetration of applied agents.

PMID- 18608735
TI  - The efficacy of pimecrolimus 1% cream plus narrow-band ultraviolet B in the
      treatment of vitiligo: a double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Recently, narrow-band ultraviolet B (NB-UVB) and topical
      immunomodulators have been successfully used in the treatment of vitiligo.
      OBJECTIVE: To determine whether the combination of pimecrolimus with NB-UVB
      accelerates the response time and/or improves the degree of response in patients
      with vitiligo. METHODS: Sixty-eight patients with vitiligo enrolled in this
      randomized, double-blind, placebo-controlled study. The patients were randomized
      into two groups and treated with NB-UVB plus either pimecrolimus or placebo for 3
      months. Tri-weekly radiation was started at 280 mJ/cm(2), with 15% increments for
      each subsequent treatment until erythema was reported or a maximum of 800 mJ/cm
      was achieved. At baseline and 6 and 12 weeks after commencement of therapy,
      vitiliginous patches were measured. RESULTS: Fifty patients completed the 3-month
      study. No significant side effects except self-limited erythema and pruritus were
      observed. After 12 weeks of treatment, repigmentation of the facial lesions was
      higher in patients treated with combined pimecrolimus and NB-UVB compared with
      the placebo plus NB-UVB group (64.3 vs 25.1%) (p < 0.05%). There was no
      statistically significant difference in the repigmentation rate between the two
      groups on other body areas. CONCLUSION: On the face, NB-UVB works better if
      combined with pimecrolimus 1% cream rather than used alone.

PMID- 18608736
TI  - Hyperkeratosis of the nipple and areola: 2 years of remission with low-dose
      acitretin and topical calcipotriol therapy.
AB  - Hyperkeratosis of the nipple and areola is a rare disorder characterized by
      verrucous thickening and brown pigmentation of the nipple and areola with unknown
      etiology. Although it is a generally asymptomatic disorder, cosmetic disfiguring
      creates a real psychological problem for young women. Moreover, treatment
      regimens are not satisfactory. Surgical treatment has been suggested as an
      initial treatment in resistant and recurrent cases because of the relapses seen
      after medical treatment. We report a case who responded satisfactorily to low
      dose acitretin and topical calcipotriol treatment with no relapses during 2 years
      of follow-up. Among all reported medical treatments and interventional
      approaches, including surgery, this is the first patient reported with 2 years of
      remission.

PMID- 18608737
TI  - Azithromycin pulses in the treatment of inflammatory and pustular acne: efficacy,
      tolerability and safety.
AB  - BACKGROUND: Azithromycin is an azalide analogous to erythromycin; it has an anti
      inflammatory action that prevents the growth of Propionibacterium acnes, a major
      microorganism involved in the pathogenesis of inflammatory acne. METHODS: An
      open, multicentric, non-comparative study was performed with 57 patients to
      evaluate the efficacy, tolerability and safety of azithromycin in the treatment
      of grade 2 inflammatory vulgar acne, using a regimen of three monthly pulses of
      500 mg for 3 consecutive days. The efficacy was evaluated using the Physician's
      Global Evaluation of Clinical Response Scale. The drug's safety was monitored by
      standard laboratory analyses and by the incidence of adverse events. RESULTS:
      Azithromycin showed a significant statistical reduction of the number of lesions
      in the different regions of the face between the basal and final visits
      (p<0.001). The laboratory changes associated with the treatment with azithromycin
      were not clinically significant. The majority of adverse events reported were
      related to the gastrointestinal and central nervous systems, and were classified
      as mild or moderate. Only two patients had to be withdrawn from the study due to
      adverse events. CONCLUSION: Three monthly pulses of azithromycin 500 mg for 3
      consecutive days is safe, well tolerated, effective and promotes increased
      patient adhesion to the treatment.

PMID- 18608738
TI  - Acanthosis nigricans associated with primary hypogonadism: successful treatment
      with topical calcipotriol.
AB  - Acanthosis nigricans is a mucocutaneous dermatosis characterized by
      hyperpigmentation and a velvety papillomatous hyperkeratosis. It is frequently
      associated with systemic diseases including malignancy and endocrinal disorders.
      We report the beneficial effect of topical calcipotriol ointment 50 mcg/g twice a
      day in acanthosis nigricans associated with primary hypogonadism.

PMID- 18608739
TI  - A case of granulomatous rosacea successfully treated with pimecrolimus cream.
AB  - A 43-year-old male attended with lesions on his face that had been present for 3
      months. On dermatological examination, multiple papules and pustules were seen on
      the forehead, nose, bilateral cheeks and lower eyelids. The patient used systemic
      clindamycin and doxycycline and topical benzoyl peroxide therapies, but the
      lesions did not regress. Routine laboratory tests were normal. Histopathological
      examination of the lesions confirmed the diagnosis of granulomatous rosacea.
      Pimecrolimus cream 1% was applied to the lesions. The regression of lesions began
      in the first month and complete improvement was observed at the end of the fourth
      month of therapy. Rosacea is a chronic, inflammatory skin disorder characterized
      by remissions and relapses. Although it is known that the disease is a treatable
      disorder, it may be resistant to standard therapies and there is a need for new
      therapy alternatives in some patients. We present a case of granulomatous rosacea
      successfully treated with pimecrolimus cream and believe that pimecrolimus may be
      a good alternative for the treatment of granulomatous rosacea.

PMID- 18608740
TI  - Enzyme kinetic and molecular modelling studies of sulphur-containing substrates
      of phenylalanine 4-monooxygenase.
AB  - Previous investigations into the binding of substrates/cofactors to the PAH
      active site have only concentrated on Phe, thienylalanine and BH(4). This is the
      first reported investigation to model aliphatic thioether amino acid substrates
      to PAH. The clearance of the thioether substrates (4.82-79.09% of Phe) in the rat
      and human (1.19-37.41% of Phe) showed species differences. The xenobiotic
      thioether substrates (SMC and SCMC) were predicted to be poor substrates for PAH
      by the molecular modelling investigation and this has now been confirmed by the
      in vitro enzyme kinetic data. However, reaction phenotyping investigations have
      found that PAH was the major enzyme involved in the metabolism of SCMC in vitro
      and in vivo.

PMID- 18608741
TI  - Design, synthesis and pharmacological evaluation of novel tetrasubstituted
      thiophene analogues as anti-inflammatory agents.
AB  - A new series of tetrasubstituted thiophene analogues (4a-4f, 5a-5f and 8a-8i)
      were designed incorporating the pharmacophoric features of COX-1 (as in
      fenamates), 5-LOX and the p38 MAP kinase inhibitors. The designed series was
      synthesized by nucleophilic addition of aryl/aroylisothiocyanate and enamine (2)
      yielding the addition product l-(alpha-Carbomethoxy-beta-aminothiocrotonoyl)
      aryl/aroyl amines (3/7); which on reaction with substituted phenacyl bromides
      gave the targeted tetrasubstituted thiophene esters (4a-4f / 8a-8i). The
      tetrasubstituted thiophenes esters (4a-4f ) on hydrolysis with one equivalent of
      potassium hydroxide solution in methanol at room temperature gave corresponding
      acids (5a-5f ). All the targeted compounds were evaluated for their anti
      inflammatory activity in carrageenin-induced rat hind paw oedema model at the
      doses of 10, 20 and 40 mg/kg body weight using standard drugs mefanamic acid and
      ibuprofen. The compounds (4c, 4e, 4f, 5f, 8a- 8i) which gave reasonable
      protection to the inflamed paw, eliciting good or moderate comparable anti
      inflammatory activity were selected for investigating their analgesic activity
      using acetic acid induced writhing response test in albino mice at 10 mg/kg dose
      using standard drug ibuprofen and in order to arrive at possible mechanism of
      their anti-inflammatory activity, in vitro antioxidant nitric oxide radical
      scavenging assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 microg/mL
      were performed using standard drug ascorbic acid.

PMID- 18608742
TI  - The strand transfer oligonucleotide inhibitors of HIV-integrase.
AB  - Retroviral integrase participates in two catalytic reactions, which require
      interactions with the two ends of the viral DNA in the 3'processing reaction, and
      with a targeted host DNA in the strand transfer reaction. The 3'-hydroxyl group
      of 2'-deoxyadenosine resulting from the specific removing of GT dinucleotide from
      the viral DNA in the processing reaction provides the attachment site for the
      host DNA in a transesterification reaction. We synthesized oligonucleotides (ONs)
      of various lengths that mimic the processed HIV-1 U5 terminus of the proviral
      long terminal repeat (LTR) and are ended by 2'-deoxyadenosine containing a 3'-O
      phosphonomethyl group. The duplex stability of phosphonomethyl ONs was increased
      by covalent linkage of the modified strand with its complementary strand by a
      triethylene glycol loop (TEG). Modified ONs containing up to 10 bases inhibited
      in vitro the strand transfer reaction catalyzed by HIV-1 integrase at nanomolar
      concentrations.

PMID- 18608743
TI  - Design and synthesis of substituted imidazole and triazole N
      phenylbenzo[d]oxazolamine inhibitors of retinoic acid metabolizing enzyme CYP26.
AB  - The design of N-phenylbenzo[d]oxazolamines as CYP26A1 inhibitors involved ligand
      docking experiments using molecular modeling (FlexX) and analysis of ligand
      interactions at the binding domain. The synthesis of the benzooxazol-2-yl-[phenyl
      imidazol-1-yl-methyl)phenyl]amines was achieved by cyclisation of the
      corresponding isothiocyanates with subsequent introduction of the haem-binding
      heterocycle. Triazole and tetrazole derivatives were also prepared for comparison
      with the lead imidazole derivative. The benzooxazol-2-yl-[phenyl-imidazol-1-yl
      methyl)phenyl]amines with small substituents in the phenyl ring were moderately
      potent CYP26A1 inhibitors (IC(50) 8 and 12 microM) and comparable with liarozole
      (IC(50) 7 microM).

PMID- 18608744
TI  - Design and synthesis of 3-pyrrol-3-yl-3H-isobenzofuran-1-ones as inhibitors of
      human cytosolic phospholipase A2alpha.
AB  - A series of 3-pyrrol-3-yl-3H-isobenzofuran-1-ones was synthesized and assessed
      for the ability to inhibit cytosolic phospholipase A(2)alpha (cPLA(2)alpha).
      Several of these compounds were found to be active in both a cell based assay and
      an isolated enzyme assay. The most potent inhibitor was the thiazolidine-2,4
      dione substituted derivative 35. With IC(50)-values of 0.7 muM and 7.3 muM in the
      cellular and isolated enzyme assay, respectively, it possesses similar inhibitory
      potency as the known cPLA(2)alpha inhibitor arachidonyltrifluoromethyl ketone
      (AACOCF(3)). Structure-activity relationship studies revealed that the evaluated
      isobenzofuran-1-ones seem to exert their cellular activities not only by a direct
      interaction with the enzyme but also by other as yet unknown mechanisms.

PMID- 18608745
TI  - Predictive QSAR modeling of CCR5 antagonist piperidine derivatives using
      chemometric tools.
AB  - Quantitative structure-activity relationship (QSAR) studies have been performed
      on piperidine derivatives (n = 119) as CCR5 antagonists. The whole data set was
      divided into a training set (75% of the dataset) and a test set (remaining 25%)
      on the basis of K-means clustering technique. Models developed from the training
      set were used to assess the predictive potential of the models using test set
      compounds. Initially classical type QSAR models were developed using structural,
      spatial, electronic, physicochemical and/or topological parameters using
      statistical methods like stepwise regression, partial least squares (PLS) and
      factor analysis followed by multiple linear regression (FA-MLR). Using
      topological and structural parameters, FA-MLR provided the best equation based on
      internal validation (Q(2) = 0.514) but the best externally validated model was
      obtained with PLS ([image omitted] = 0.565). When structural, physicochemical,
      spatial and electronic descriptors were used, the best Q(2) value (0.562) was
      obtained from the stepwise regression derived model whereas the best [image
      omitted] value (0.571) came from the PLS model. When topological descriptors were
      used in combination with the structural, physicochemical, spatial and electronic
      descriptors, the best Q(2) and [image omitted] values obtained were 0.530
      (stepwise regression) and 0.580 (PLS) respectively. Attempt was made to develop
      3D-QSAR models using molecular shape analysis descriptors in combination with
      structural, physicochemical, spatial and electronic parameters. Linear models
      were developed using genetic function algorithm coupled with multiple linear
      regression. However, the results from the 3D-QSAR study were not superior to
      those of the classical QSAR models. Finally, artificial neural network was
      employed for development of nonlinear models. The ANN models showed acceptable
      values of squared correlation coefficient for the observed and predicted values
      of the test set compounds. From the view point of external predictability,
      selected ANN models were superior to the linear QSAR models. All reported models
      satisfy the criteria of external validation as recommended by Golbraikh and
      Tropsha (J Mol Graphics Mod 2002; 20: 269-276), whereas the majority of the
      models have modified r(2) ([image omitted] ) value of the test set for external
      validation more than 0.5 as suggested by Roy and Roy (QSAR Comb Sci 2008; 27: 302
      313).

PMID- 18608746
TI  - Inhibitory effects of flavonoids on aldehyde oxidase activity.
AB  - Flavonoids are an important group of natural compounds that can interfere with
      the activity of some enzymes. In this study, effects of various flavonoids on
      aldehyde oxidase (AO) activity were evaluated in vitro. AO was partially purified
      from guinea pig liver. The effects of 12 flavonoids from three subclasses of
      flavon-3-ol, flavan-3-ol and flavanone on the oxidation of vanillin and
      phenanthridine as substrates of AO and xanthine as a substrate of xanthine
      oxidase (XO) were investigated spectrophotometrically. Among the 12 flavonoids,
      myricetin and quercetin were the most potent inhibitors of both AO and XO. In
      general, the oxidation of vanillin was more inhibited by flavonoids than that of
      phenanthridine. Almost all of the flavonoids inhibited AO activity more potently
      than XO, which was more evident with non-planner flavanols. A planner structure
      seems to be essential for a potent inhibitory effect and any substitution by
      sugar moieties reduces the inhibitory effects. This study could provide a new
      insight into AO natural inhibitors with potential to lead to some food-drug
      interactions.

PMID- 18608747
TI  - His22 of TLXI plays a critical role in the inhibition of glycoside hydrolase
      family 11 xylanases.
AB  - Recently, a novel wheat thaumatin-like protein, TLXI, which inhibits microbial
      glycoside hydrolase family (GH) 11 xylanases has been identified. It is the first
      xylanase inhibitor that exerts its inhibition in a non-competitive way. In the
      present study we gained insight into the interaction between TLXI and xylanases
      via combined molecular modeling and mutagenic approaches. More specifically, site
      specific mutation of His22, situated on a loop which distinguishes TLXI from
      other, non-inhibiting, thaumatin-like proteins, and subsequent expression of the
      mutant in Pichia pastoris resulted in a protein lacking inhibition capacity. The
      mutant protein was unable to form a complex with GH11 xylanases. Based on these
      findings, the interaction of TLXI with GH11 xylanases is discussed.

PMID- 18608748
TI  - 1-Arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones as leads for
      developing cytotoxins and anticonvulsants.
AB  - Various substituted 1-arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones
      3a-h, 1-benzyl-2,3-dioxo-2,3-dihydroindole N(4)-aryl thiosemicarbazones 4a-i and
      1-benzyl-2,3-dioxy-2,3-dihydroindole N(4)-cyclohexylthiocarbazone 5 were
      synthesized. All of these compounds were evaluated against human Molt 4/C8 and
      CEM T-lymphocytes as well as murine L1210 leukemia cells. Nearly 40% of these
      compounds possess low micromolar IC(50) values and some are either more potent
      than, or equipotent with, melphalan. Various correlations between the structures
      of these compounds and cytotoxic potencies were obtained which included the use
      of QSAR and molecular modeling techniques. Representative compounds displayed
      anticonvulsant properties in rats and were well tolerated by these animals. The
      encouraging biodata noted affords adequate rationale for outlining guidelines for
      further development of these molecular scaffolds.

PMID- 18608749
TI  - QSAR study on dual SET and NET reuptake inhibitors: an insight into the
      structural requirement for antidepressant activity.
AB  - Monoamine transporters have emerged as important drug targets with a multitude of
      therapeutic potentials for their inhibitors. With the purpose of designing new
      chemical entities with enhanced inhibitory potencies against norepinephrine and
      serotonin transporters, the QSAR study carried out on N-arylmethylpiperidinamine
      derivatives as known inhibitors of these transporters is presented. The developed
      model was validated by standard QSAR parameters and through a detailed structural
      analysis on how it reproduces and explains the differences in the experimentally
      known activity data. The model showed a good correlative and predictive ability
      having a squared cross validated correlation co-efficient of 0.716 and 0.700
      respectively for SET and NET inhibition. The squared conventional correlation
      coefficient was found to be 0.731 for SET antagonism and 0.777 for norepinephrine
      reuptake inhibition. The study confirmed that the serotonin reuptake inhibitory
      activity exhibited by the series is largely explained by steric factors of
      substituents emphasizing the role of size and shape of the inhibitors in making
      effective inhibitor-SET binding interactions whereas substituent lipophilicity
      was found to govern inhibitor-NET interaction chemistry. A detailed comparative
      investigation was made between the two models and the insights gleaned from the
      study could be usefully employed to design inhibitors with a much more enhanced
      potency and selectivity.

PMID- 18608750
TI  - QSAR of aromatic substances: EGFR inhibitory activity of quinazoline analogues.
AB  - The flip regression procedure that we used earlier for handling the xanthones
      system has been applied to phenylaminoquinazoline analogues. It is known that the
      substituents at the 6- and 7- positions of the polycyclic system have been
      identified as the most important structural features. The steric as well as the
      electrostatic interactions proved to be the most important for the inhibitory
      effect. In this contribution it is shown that the orientation of nodes in their
      occupied pi orbitals, and also the energies of these orbitals explains a further
      large portion of the variance in their inhibitory activity.

PMID- 18608751
TI  - A comparison of the therapeutic and reactivating efficacy of newly developed
      bispyridinium compounds (K206, K269) with currently available oximes against
      tabun in rats and mice.
AB  - The potency of newly developed bispyridinium compounds (K206, K269) in
      reactivating tabun-inhibited acetylcholinesterase and eliminating tabun-induced
      lethal toxic effects was compared with commonly used oximes (obidoxime,
      trimedoxime, the oxime HI-6) using in vivo methods. Studies which determined
      percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned
      rats showed that the reactivating efficacy of both newly developed oximes is
      comparable with obidoxime and trimedoxime in blood but lower than the
      reactivating potency of trimedoxime and obidoxime in the diaphragm and brain.
      Nevertheless, the differences in reactivating efficacy of obidoxime, trimedoxime
      and K206 was not significant while the potency of K269 to reactivate tabun
      inhibited acetylcholinesterase was significantly lower. Both newly developed
      oximes were also found to be relatively efficacious in elimination of the lethal
      toxic effects in tabun-poisoned mice. Their therapeutic efficacy corresponds to
      the therapeutic potency of obidoxime. The oxime HI-6, relatively efficacious
      against soman, did not seem to be an adequately effective oxime in reactivation
      of tabun-inhibited AChE and to counteract lethal effects of tabun. Both newly
      developed oximes (K206, K269) are significantly more efficacious in reactivating
      tabun-inhibited AChE in rats and to eliminate lethal toxic effects of tabun in
      mice than the oxime HI-6 but their reactivating and therapeutic potency does not
      prevail over the effectiveness of currently available obidoxime and trimedoxime
      and, therefore, they are not suitable for their replacement of commonly used
      oximes for the treatment of acute tabun poisoning.

PMID- 18608752
TI  - Carbonic anhydrase inhibitors. Biphenylsulfonamides with inhibitory action
      towards the transmembrane, tumor-associated isozymes IX possess cytotoxic
      activity against human colon, lung and breast cancer cell lines.
AB  - Reaction of 4,4-biphenyl-disulfonyl chloride with aromatic/heterocyclic
      sulfonamides also incorporating a free amino group, such as 4
      aminobenzenesulfonamide, 4-aminoethyl-benzenesulfonamide, 6-chloro-4-aminobenzene
      1,3-disulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded bis
      sulfonamides which have been tested as inhibitors of the zinc enzyme carbonic
      anhydrase (CA, EC 4..2.1.1). The compounds were rather modest inhibitors of
      isozymes CA I and XII, but were more efficient as inhibitors of the cytosolic CA
      II and transmembrane, tumor-associated CA IX (inhibition constants in the range
      of 21-129 nM gainst hCA II, and 23-79 nM against hCA IX, respectively). The new
      bis-sulfonamides also showed inhibition of growth of several tumor cell lines (ex
      vivo), with GI(50) values in the range of 0.74-10.0 microg/mL against the human
      colon cancer cell line HCT116, the human lung cancer cell line H460 and the human
      breast cancer cell line MCF-7.

PMID- 18608753
TI  - Effects of some analgesic anaesthetic drugs on human erythrocyte glutathione
      reductase: an in vitro study.
AB  - Inhibitory effects of some analgesic and anaesthetic drugs on human erythrocyte
      glutathione reductase were investigated. For this purpose, human erythrocyte
      glutathione reductase was initially purified 2139-fold in a yield of 29% by using
      2', 5'-ADP Sepharose 4B affinity gel and Sephadex G-200 gel filtration
      chromatography. SDS polyacrylamide gel electrophoresis confirmed the purity of
      the enzyme by sharing a single band. A constant temperature (+4 degrees C) was
      maintained during the purification process. Diclofenac sodium, ketoprofen,
      lornoxicam, tenoxicam, etomidate, morphine and propofol exhibited inhibitory
      effects on the enzyme in vitro using the Beutler assay method. K(i) constants and
      IC(50) values for drugs were determined from Lineweaver-Burk graphs and plotting
      activity % versus [I] graphs, respectively. The IC(50) values of diclofenac
      sodium, ketoprofen, lornoxicam, propofol, tenoxicam, etomidate and morphine were
      7.265, 6.278, 0.3, 0.242, 0.082, 0.0523 and 0.0128 mM and the K(i) constants were
      23.97 +/- 2.1, 22.14 +/- 7.6, 0.42 +/- 0.18, 0.418 +/- 0.056, 0.13 +/- 0.025,
      0.0725 +/- 0.0029 and 0.0165 +/- 0.0013 mM, respectively. While diclofenac
      sodium, ketoprofen, lornoxicam, tenoxicam etomidate and morphine showed
      competitive inhibition, propofol displayed noncompetitive inhibition.

PMID- 18608754
TI  - Kinetic properties and inhibition of the dimeric dUTPase-dUDPase from
      Campylobacter jejuni.
AB  - The enzyme deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) catalyses
      the hydrolysis of dUTP to dUMP and PPi thus controlling the incorporation of
      uracil into DNA genomes. In Campylobacter jejuni dUTPase exhibits structural
      properties of dimeric proteins characteristic of protozoa of the Kinetoplastidae
      family. In the present study we perform a kinetic analysis of Campylobacter
      dUTPase using the continuous spectrophotometric method and show that the enzyme
      is highly specific for deoxyuridine nucleotides. The Michaelis-Menten constant
      for dUTP was 0.66 microM while the k(cat) was 12.3 s(- 1). dUDP was also
      efficiently hydrolysed although the specificity constant, k(cat)/K(m), was five
      fold lower than for dUTP. The reaction product and the non hydrolysable analogue
      alpha,beta imido dUDP are potent inhibitors of the enzyme while several analogues
      of dUMP with substituents at the 3'- and 5'-positions active against trimeric
      dUTPases, show poor inhibitory activity. Apparent structural and kinetic
      differences with other eukaryotic dUTPases suggest that the present enzyme might
      be exploited as a target for new drugs against campylobacteriosis.

PMID- 18608755
TI  - New tryptophanase inhibitors: towards prevention of bacterial biofilm formation.
AB  - Tryptophanase (tryptophan indole-lyase, Tnase, EC 4.1.99.1), a bacterial enzyme
      with no counterpart in eukaryotic cells, produces from L-tryptophan pyruvate,
      ammonia and indole. It was recently suggested that indole signaling plays an
      important role in the stable maintenance of multicopy plasmids. In addition,
      Tnase was shown to be capable of binding Rcd, a short RNA molecule involved in
      resolution of plasmid multimers. Binding of Rcd increases the affinity of Tnase
      for tryptophan, and it was proposed that indole is involved in bacteria
      multiplication and biofilm formation. Biofilm-associated bacteria may cause
      serious infections, and biofilm contamination of equipment and food, may result
      in expensive consequences. Thus, optimal and specific factors that interact with
      Tnase can be used as a tool to study the role of this multifunctional enzyme as
      well as antibacterial agents that may affect biofilm formation. Most known quasi
      substrates inhibit Tnase at the mM range. In the present work, the mode of Tnase
      inhibition by the following compounds and the corresponding Ki values were: S
      phenylbenzoquinone-L-tryptophan, uncompetitively, 101 microM; alpha-amino-2-(9,10
      anthraquinone)-propanoic acid, noncompetitively, 174 microM; L-tryptophane
      ethylester, competitively, 52 microM; N-acetyl-L-tryptophan, noncompetitively, 48
      microM. S-phenylbenzoquinone-L-tryptophan and alpha-amino-2-(9,10-anthraquinone)
      propanoic acid were newly synthesized.

PMID- 18608757
TI  - Synthesis and preliminary evaluation of new ursolic and oleanolic acids
      derivatives as antileishmanial agents.
AB  - A series of new ursolic and oleanolic acids derivatives was synthesized via
      ursolic or oleanolic acids, previously extracted from South American Ilex
      species. These new compounds were tested for in vitro antiparasitic activity on
      Leishmania amazonensis and Leishmania infantum strains. Some of these compounds
      showed activity against the promastigote forms of L. amazonensis or L. infantum,
      with IC(50) ranging from 5 to 12 microM. As expected, most of the compounds
      showed a significant level of cytotoxicity against monocytes (IC(50) = 2-50
      microM). From a structure-activity relationships point of view, these
      pharmacological results enlightened mainly the importance of an acetylation at
      position 3 of the oleanolic acid skeleton in the activity against the L.
      amazonensis strain, and of a bis-(3-aminopropyl)piperazine moiety on the
      carboxylic function of ursolic acid against the L. infantum strain.

PMID- 18608756
TI  - Comparative study of the inhibitory effect of antidepressants on cholinesterase
      activity in Bungarus sindanus (krait) venom, human serum and rat striatum.
AB  - Cholinesterases are divided into two classes based on differences in their
      substrate specificity and tissue distribution: acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE). These enzymes may be inhibited by several
      compounds, such as antidepressants. The antidepressants paroxetine, imipramine,
      clomipramine and sertraline inhibited both venom AChE as well as human serum BChE
      in a concentration-dependent manner but had no effect on AChE in the rat brain
      striatum. The IC(50) of venom calculated for imipramine was 0.3 mM, paroxetine
      0.38 mM, clomipramine 0.34 mM and sertraline 0.35 mM. Analysis of kinetic data
      indicated that the inhibition caused by sertraline and paroxetine was mixed, i.e.
      K(m) values increased and V(max) decreased in a concentration dependent manner.
      Imipramine and clomipramine exhibited competitive inhibition, i.e. K(m) values
      increased and V(max) remained constant. The present results suggest that these
      therapeutic agents used for depression can also be considered as inhibitors of
      snake venom and human serum cholinesterase.

PMID- 18608758
TI  - Anti-tubercular activity of ruthenium (II) complexes with polypyridines.
AB  - A series of nine polypyridyl-ruthenium (II) complexes (N-ligands = 2,2'
      bipyridines; 2,2'-6',2'-terpyridines, di-alkyloxy-2,2'-6,2-bipyridine-3,3'-di
      carboxylates), were tested against Mycobacterium tuberculosis (MBT). The complex
      (11) showed remarkable activity against MBT as compared to other complexes, (1
      10). The aquo ligand of complex (11), as opposed to other chloro and acetonitrile
      derivatives, appears to play a key role in the antitubercular potency of this new
      class of metal-based compounds.

PMID- 18608759
TI  - Cytotoxic evaluation of sarcodifurines A and B, two novel dihydrofuroquinolines
      from Sarcomelicope follicularis (Rutaceae).
AB  - Sarcodifurines A and B are two original dihydrofuroquinolines isolated from
      Sarcomelicope follicularis, a New Caledonian tree. The cytotoxicity and
      antiproliferative activity of these two alkaloids were investigated against 8
      distinct cell lines representative of the most frequent solid tumors developing
      in human. Cytotoxicity of sarcodifurines was low on the 8 cell lines, with, for
      example, less than 10% of the total cells killed after 24 h exposure at 10 microM
      and IC(50) approximately 7.10(-5) M (MCF-7 and MDA MB 231 cell lines).
      Proliferation studies confirmed that sarcodifurines had a weak effect on cancer
      cells growth, with less than 5% growth inhibition at 10 microM. Sarcodifurine A
      activity was comparable to that of Sarcodifurine B, in term of cytotoxicity and
      antiproliferative activity on all cell lines. In spite of the weak activity of
      sarcodifurines and furoquinolines, rationalized pharmacomodulations to obtain
      planar analogs could lead to efficient topoisomerases inhibitors and DNA
      intercalants.

PMID- 18608760
TI  - Measurement of antioxidant ability of melatonin and serotonin by the DMPD and
      CUPRAC methods as trolox equivalent.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is the chief secretory product of the
      pineal gland and synthesized enzymatically from serotonin (5-hydroxytryptamine).
      These indoleamine derivatives play an important role in the prevention of
      oxidative damage. In the present study, DMPD radical scavenging and cupric ion
      (Cu(2+)) reducing ability of melatonin and serotonin as trolox equivalent
      antioxidant activity (TEAC) was investigated. Melatonin and serotonin
      demonstrated 73.5 and 127.4 microg/mL trolox equivalent DMPD( radical+)
      scavenging activity at the concentration of 100 microg/mL. Also, at the same
      concentration, melatonin and serotonin showed 14.41 and 116.09 microg/mL trolox
      equivalent cupric ion (Cu(2+)) reducing ability. These results showed that
      melatonin and serotonin had marked DMPD(radical+) radical scavenging and cupric
      ions (Cu(2+)) reducing ability. Especially, serotonin had higher DMPD radical
      scavenging and cupric ions (Cu(2+)) reducing activity than melatonin because of
      its phenolic group.

PMID- 18608761
TI  - Development of linear and nonlinear predictive QSAR models and their external
      validation using molecular similarity principle for anti-HIV indolyl aryl
      sulfones.
AB  - Quantitative structure-activity relationship (QSAR) studies have been carried out
      on indolyl aryl sulfones, a class of novel HIV-1 non-nucleoside reverse
      transcriptase inhibitors, using physicochemical, topological and structural
      parameters along with appropriate indicator variables. The statistical tools used
      were linear methods (e.g., stepwise regression analysis, partial least squares
      (PLS), factor analysis followed by multiple regression (FA-MLR), genetic function
      approximation combined with multiple linear regression (GFA-MLR) and GFA followed
      by PLS or G/PLS and nonlinear method (artificial neural network or ANN). In case
      of physicochemical parameters, GFA-MLR generated the best Equation (n = 97, R(2)
      = 0.862, Q(2) = 0.821). Using topological parameters, the best Equation (based on
      leave-one-out Q(2)) was obtained with stepwise regression technique (n = 97, R(2)
      = 0.867, Q(2) = 0.811). When topological and physicochemical parameters were used
      in combination, statistical quality increased to a great extent (n = 97, R(2) =
      0.891, Q(2) = 0.849 from stepwise regression). Furthermore, the whole dataset had
      been divided into test (25% of whole dataset) and training (remaining 75%) sets.
      Models were developed based on the training set and predictive potential of such
      models was checked from the test set. The selection of the training set was based
      on K-means clustering of the standardized descriptors (topological and
      physicochemical). In this case also the best results were obtained with stepwise
      regression (n = 72, R(2) = 0.906, Q(2) = 0.853) but external predictive capacity
      of this model ([image omitted] ) was inferior to the model developed from GFA-MLR
      technique (R(2) = 0.883, Q(2) = 0.823, [image omitted] ). However, the squared
      regression coefficient between observed activity and predicted activity values of
      the test set compounds for the best linear model, i.e., GFA-MLR (r(2) = 0.736)
      was lower in comparison to the best nonlinear model developed using artificial
      neural network (r(2) = 0.781). Thus, based on external validation, the ANN models
      were superior to the linear models. The predictive potential of the best linear
      Equation (stepwise regression model) was superior to that of the previously
      published CoMFA (Q(2) = 0.81, SDEP(Test) = 0.89) on the same data set (Ragno R.
      et al., J Med Chem 2006, 49, 3172-3184). Furthermore, the physicochemical
      parameter based models also supported the previous observations based on docking
      (Ragno R. et al., J Med Chem 2005, 48, 213-223).

PMID- 18608762
TI  - The convenient synthesis and evaluation of the anticancer activities of new
      resveratrol derivatives.
AB  - In the present study we report the simple synthesis and antitumour activity of
      novel stilbene derivatives 13-22. The key synthetic strategies involved Wadsworth
      Horner-Emmons condensation and coupling reactions in high yields. All compounds
      showed significant growth inhibition on human tumour cell lines, with the most
      potent compound (19) exhibiting an IC(50) of 5.7 microM-11.4 microM in vitro.

PMID- 18608763
TI  - Topological descriptors in modeling malonyl coenzyme A decarboxylase inhibitory
      activity: N-Alkyl-N-(1,1,1,3,3,3-hexafluoro-2-hydroxypropylphenyl)amide
      derivatives.
AB  - The malonyl-CoA decarboxylase (MCD) inhibition activity of derivatives of N-alkyl
      N-(1,1,1,3,3,3-hexafluoro-2-hydroxypropylphenyl)amide has been analyzed through
      combinatorial protocol in multiple linear regression (CP-MLR) using different
      topological descriptors obtained from Dragon software for the energy minimized 3D
      structures of these molecules. Among the topological descriptor classes
      considered in the study, the MCD inhibition activity is correlated with simple
      topological descriptors (TOPO) and 2D-autocorrelation descriptors (2DAUTO). The
      complementary information contents having neighborhood symmetry of 2-order, CIC2
      from the TOPO class, the Geary autocorrelations-lag 8, weighted by atomic
      Sanderson electronegativities, GATS8e and the Moran autocorrelations-lag 6,
      weighted by atomic Sanderson electronegativities, MATS6e both from 2DAUTO class
      have contributed significantly in the development of a statistical significant
      model.

PMID- 18608764
TI  - Modeling of vascular endothelial growth factor receptor 2 (VEGFR2) kinase
      inhibitory activity of 2-anilino-5-aryloxazoles using chemometric tools.
AB  - The structure-activity models of the VEGFR2 kinase inhibitory activity of the
      derivatives of 2-anilino-5-aryloxazole have been investigated using Combinatorial
      Protocol in Multiple Linear Regression (CP-MLR) with nearly 500 topological
      descriptors which were calculated from DRAGON software. Among the descriptor
      classes considered collectively in the study, the inhibitory activity was,
      however, correlated with simple functional (FUN), topological (TOPO), atom
      centered fragments (ACF), molecular walk counts (MWC) and 2D-autocorrelation (2D
      AUTO) descriptors. The developed models and participating descriptors in them
      have suggested that the substitutional modifications in the 2-anilino-5
      aryloxazole moiety may have sufficient scope in optimization of prevailing
      inhibitory activity of these analogues.

PMID- 18608765
TI  - Synthesis and stability assay of 4-methylumbelliferyl (1-->3)-beta-D
      pentaglucoside.
AB  - The synthesis and stability of 4-methylumbelliferyl (1 --> 3)-beta-D
      pentaglucoside 3 are described. The (1 --> 3)-beta-D-glucan isolated from the
      cell walls of Saccharomyces cerevisiae was recovered from the aqueous medium as
      water-insoluble particles by the spray drying (GS) method. The acid-solubilized
      (1 --> 3)-beta-D-oligoglucosides were prepared by partial acid hydrolysis of
      glucan. The peracetylated (1 --> 3)-beta-D-pentaglucoside 1 was obtained by
      isolation of peracetylated (1 --> 3)-beta-D-oligoglucoside mixture. The
      peracetylated 4-methylumbelliferyl (1 --> 3)-beta-D-pentaglucoside 2 was
      synthesized by treating compound 1 with the 4-methylumbelliferone and a Lewis
      acid (SnCl4) catalyst. NaOMe in dry methanol was used for the deacetylation of
      the blocked derivative, to give the target compound 3 in an overall yield of 35%.
      Activity assays with beta-glucosidase indicated that compound 3 was much more
      stable than the corresponding pentasaccharide.

PMID- 18608766
TI  - CoMFA and CoMSIA 3D-QSAR analysis on hydroxamic acid derivatives as urease
      inhibitors.
AB  - Urease (EC 3.5.1.5) serves as a virulence factor in pathogens that are
      responsible for the development of many diseases in humans and animals. Urease
      allows soil microorganisms to use urea as a source of nitrogen and aid in the
      rapid break down of urea-based fertilizers resulting in phytopathicity. It has
      been well established that hydroxamic acids are the potent inhibitors of urease
      activity. The 3D-QSAR studies on thirty five hydroxamic acid derivatives as known
      urease inhibitors were performed by Comparative Molecular Field Analysis (CoMFA)
      and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods to
      determine the factors required for the activity of these compounds. The CoMFA
      model produced statistically significant results with cross-validated (q(2))
      0.532 and conventional (r(2)) correlation coefficients 0.969.The model indicated
      that the steric field (70.0%) has greater influence on hydroxamic acid inhibitors
      than the electrostatic field (30.0%). Furthermore, five different fields: steric,
      electrostatic, hydrophobic, H-bond donor and H-bond acceptor assumed to generate
      the CoMSIA model, which gave q(2) 0.665 and r(2) 0.976.This model showed that
      steric (43.0%), electrostatic (26.4%) and hydrophobic (20.3%) properties played a
      major role in urease inhibition. The analysis of CoMFA and CoMSIA contour maps
      provided insight into the possible modification of the hydroxamic acid
      derivatives for improved activity.

PMID- 18608767
TI  - Inhibitory effects on mushroom tyrosinase by flavones from the stem  barks of
      Morus lhou (S.) Koidz.
AB  - Five flavones displaying tyrosinase inhibitory activity were isolated from the
      stem barks of Morus lhou (S.) Koidz., a cultivated edible plant. The isolated
      compounds were identified as mormin (1), cyclomorusin (2), morusin (3), kuwanon C
      (4), and norartocarpetin (5). Mormin (1) was characterized as a new flavone
      possesing a 3-hydroxymethyl-2-butenyl at C-3. The inhibitory potencies of these
      flavonoids toward monophenolase activity of mushroom tyrosinase were
      investigated. The IC50 values of compounds 1-5 for monophenolase activity were
      determined to be 0.088, 0.092, 0.250, 0.135 mM, and 1.2 microM, respectively.
      Mormin (1), cyclomorusin (2), kuwanon C (4) and norartocarpetin (5) exhibited
      competitive inhibition characteristics. Interestingly norartocarpetin (5) showed
      a time-dependent inhibition against oxidation of L-tyrosine: it also operated
      under the enzyme isomerization model (k5 = 0.8424 min(-1), k6 = 0.0576 min(-1),
      K(app)(i) = 1.354 microM).

PMID- 18608768
TI  - Synthesis and antimicrobial studies of novel 1-benzhydryl-piperazine sulfonamide
      and carboxamide derivatives.
AB  - A series of novel substituted 1-benzhydryl-piperazine sulfonamide 8(a-f) and
      benzamides 9(a-h) were synthesized and their antimicrobial activities evaluated
      in vitro by paper disc diffusion and micro dilution method against standard
      strains of Gram-positive (Staphylococcus aureus ATCC 25953, Staphylococcus
      epidermis 25212, Bacillus cereus 11778, Bacillus substilis 6051) and Gram
      negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 2853, Proteus
      vulgaris ATCC 2853 and Salmonella typhi ATCC 9484) bacteria. Among the
      synthesized new compounds 8d, 8e, 9c, 9e, 9f and 9 h showed potent antimicrobial
      activities compared to the standard drug streptomycin.

PMID- 18608769
TI  - A solid phase parallel synthesis of diverse amides as dopamine D3 receptor
      ligands.
AB  - A solid phase parallel synthesis using SynPhase technology was used to couple a
      series of 21 carboxylic with three different 4-(4-arylpiperazinyl)butanamines.
      The resulting library was evaluated as dopamine D(3) receptor ligands giving rise
      to several compounds with affinities in the low nanomolar concentration range (9e
      and 9n with binding affinities at D(3) receptors of 0.10 and 0.35 nM
      respectively).

PMID- 18608770
TI  - Synthesis of azatricyclodiones & octahydro-benzo[f]isoindoles and their
      antimicrobial evaluation.
AB  - A series of azatricyclodiones and octahydro-benzo[f]isoindoles have been
      synthesized by (4+2) Diels-Alder cycloaddition of maleimides with furfuryl amine.
      Reaction of azatricyclodiones with isocyanates led to the respective ureides. All
      of the compounds were screened against a number of bacteria and fungi. One of the
      compounds (2) displayed moderate antitubercular activity while two compounds (2)
      and (4) inhibited the fungal growth at 25 MUg/mL.

PMID- 18608771
TI  - In silico studies of urease inhibitors to explore ligand-enzyme interactions.
AB  - In continuation of our previous study on the urease inhibition by a number of
      chalcones, 2,3-dihydro-1,5-benzothiazepines and 2,3,4,5-tetrahydro-1,5
      benzothiazepines, FlexX docking has been exploited to get a deeper insight into
      the mechanism of their inhibitory action. A comparison of the IC(50) values of
      the active compounds reveals that, of the three classes of compounds studied, 2,3
      dihydro-1,5-benzothiazepines were the most potent urease inhibitors. An in silico
      examination of these compounds showed that the activity is related to the
      interaction of ligand with the nickel metallocentre, its interaction with two
      amino acid residues, Asp224 and Cys322, in addition to the orientation of rings A
      and B in the catalytic core of the enzyme. The most active compound 2,3-dihydro
      1,5-benzothiazepine (4) anchor tightly through a network of interactions with
      Ni701 and Ni702. This includes a number of hydrogen bonds and hydrophobic
      contacts with the amino acid residues in its vicinity. For their reduced analogs,
      the difference in the activity of different diastereomers has been observed to be
      configuration-dependent. This may be ascribed mainly to the difference in the
      orientation of ring B of the two stereoisomers and the extent of their
      interaction with Asp224 and Cys322 present in the catalytic core of the enzyme.

PMID- 18608772
TI  - A high density assay format for the detection of novel cytotoxic  agents in large
      chemical libraries.
AB  - In response to the need for inexpensive high throughput assays for anti-cancer
      drug screening, a 1536-well microtiter plate based assay utilizing the Alamar
      Blue fluorescent dye as a measure of cellular growth was validated in 10 microL
      assay volume. Its robustness was assessed in a screen against a library of 2000
      known bioactives; with an overall Z' value of 0.89 for assay robustness, several
      known cytotoxic agents were identified including and not limited to
      anthracyclines, cardiac glycosides, gamboges, and quinones. To further test the
      sensitivity of the assay, IC50 determinations were performed in both 384-well and
      1536-well formats and the obtained results show a very good correlation between
      the two density formats. These findings demonstrate that this newly developed
      assay is simple to set up, robust, highly sensitive and inexpensive. It could
      potentially provide a rapid way to screen established and primary tumor cell
      lines against large chemical libraries.

PMID- 18608773
TI  - Norditerpenoid alkaloids from the roots of Aconitum heterophyllum   Wall with
      antibacterial activity.
AB  - Two new aconitine-type norditerpenoid alkaloids 6-dehydroacetylsepaconitine (1)
      and 13-hydroxylappaconitine (2), along with three known norditerpenoid alkaloids
      lycoctonine, delphatine and lappaconitine were isolated from the roots of the
      Aconitum heterophyllum Wall. These compounds exhibited significant antibacterial
      activity. The structure of compound 1 and 2 were deduced on the basis of their
      spectral data.

PMID- 18608774
TI  - Synthesis and anticandidal activity of some imidazopyridine derivatives.
AB  - New hydrazide derivatives of imidazo[1,2-a]pyridine have been synthesized and
      evaluated for anticandidal activity. The reaction of imidazo[1,2-a]pyridine-2
      carboxylic acid hydrazides with various benzaldehydes gave N
      (benzylidene)imidazo[ 1,2-a]pyridine-2-carboxylic acid hydrazide derivatives.
      Their anticandidal activities against Candida albicans and Candida glabrata
      (isolates obtained from Osmangazi University, Faculty of Medicine, Eskisehir,
      Turkey), Candida albicans (ATCC 90028), Candida utilis (NRLL Y-900), Candida
      tropicalis (NRLL Y-12968), Candida krusei (NRLL Y-7179), Candida zeylanoides
      (NRLL Y-1774), and Candida parapsilosis (NRLL Y-12696) were investigated.

PMID- 18608775
TI  - New antibacterial pentacyclic triterpenes from Myricaria elegans  Royle.
      (tamariscineae).
AB  - Two new pentacyclic triterpenes eleganene-A (1) and eleganene-B (2), along with
      four known pentacyclic triterpenes betulin (3), ursolic acid (4), erythrodiol (5)
      and corosolic acid (6) were isolated from the aerial parts of Myricaria elegans.
      These compounds exhibited significant antibacterial activity. The structure of
      compounds 1 and 2 were deduced on the basis of their spectral analysis.

PMID- 18608776
TI  - Particular interaction between pyrimethamine derivatives and quadruple mutant
      type dihydrofolate reductase of Plasmodium falciparum: CoMFA and quantum chemical
      calculations studies.
AB  - Comparative molecular field analysis (CoMFA) was performed on twenty-three
      pyrimethamine (pyr) derivatives active against quadruple mutant type (Asn51Ile,
      Cys59Arg, Ser108Asn, Ile164Leu) dihydrofolate reductase of Plasmodium falcipaarum
      (PfDHFR). The represented CoMFA models were evaluated based on the various three
      different probe atoms, C(sp3) (+1), O(sp3) (-1) and H (+1), resulting in the best
      model with combined three types of probe atoms. The statistical results were
      r(2)(cv) = 0.702, S(press) = 0.608, r(2)(nv) = 0.980, s = 0.156, and r(2)(test
      set) = 0.698 which can explain steric contribution of about 50%. In addition, an
      understanding of particular interaction energy between inhibitor and surrounding
      residues in the binding pocket was performed by using MP2/6-31G(d,p) quantum
      chemical calculations. The obtained results clearly demonstrate that Asn108 is
      the cause of pyr resistance with the highest repulsive interaction energy.
      Therefore, CoMFA and particular interaction energy analyses can be useful for
      identifying the structural features of potent pyr derivatives active against
      quadruple mutant type PfDHFR.

PMID- 18608777
TI  - Mono- (Ag, Hg) and di- (Cu, Hg) valent metal ions effects on the activity of jack
      bean urease. Probing the modes of metal binding to the enzyme.
AB  - The inhibition of urease by heavy metal ions has been habitually ascribed to the
      reaction of the ions with enzyme thiol groups, resulting in the formation of
      mercaptides. To probe the modes of metal binding to the enzyme, in this work the
      reaction of mono- (Ag, Hg) and di- (Cu, Hg) valent metal ions with jack bean
      urease was studied. The enzyme was reacted with different concentrations of the
      metal ions for different periods of times, when its residual activity was assayed
      and thiol content titrated. The titration carried out with DTNB was done to
      examine the involvement of urease thiol groups in metal ion binding. The binding
      was further probed by reactivation of the metal ion-enzyme complexes with DTT,
      EDTA and dilution. The results are discussed in terms of the HSAB concept. In
      inhibiting urease the metal ions showed a common feature in that they inhibited
      the enzyme within a comparable micromolar range, and also in that their
      inhibition was multisite. By contrast, the main distinguishing feature in their
      action consisted of the involvement of enzyme thiol groups in the reaction. Hg
      (2+) and Hg2(2+) inhibition was found thoroughly governed by the reaction with
      the enzyme thiols, and the complete loss of enzyme activity involved all thiols
      available in the enzyme under non-denaturating conditions. In contrast, Ag+ and
      Cu2+ ions for the complete inactivation of the enzyme required 53 and 60% of
      thiols, respectively. Accordingly, Ag+ and Cu2+ binding to functional groups in
      urease other than thiols, i.e. N- and O-containing groups, cannot be excluded.
      Based on the reactivation experiments this seems particularly likely for Cu2+,
      whose concurrent binding to thiols and other groups might distort the
      architecture of the active site (the mechanism of which remains to be elucidated)
      resulting in the observed inhibitory effects.

PMID- 18608778
TI  - Simple inhibitors of histone deacetylase activity that combine features  of short
      chain fatty acid and hydroxamic acid inhibitors.
AB  - Butyric acid and trichostatin A (TSA) are anti-cancer compounds that cause the
      upregulation of genes involved in differentiation and cell cycle regulation by
      inhibiting histone deacetylase (HDAC) activity. In this study we have synthesized
      and evaluated compounds that combine the bioavailability of short-chain fatty
      acids, like butyric acid, with the bidentate binding ability of TSA. A series of
      analogs were made to examine the effects of chain length, simple aromatic cap
      groups, and substituted hydroxamates on the compounds' ability to inhibit rat
      liver HDAC using a fluorometric assay. In keeping with previous structure
      activity relationships, the most effective inhibitors consisted of longer chains
      and hydroxamic acid groups. It was found that 5-phenylvaleric hydroxamic acid and
      4-benzoylbutyric hydroxamic acid were the most potent inhibitors with IC50's of 5
      microM and 133 microM respectively.

PMID- 18608779
TI  - Quinic acid derivatives from Saussurea triangulata attenuates glutamate-induced
      neurotoxicity in primary cultured rat cortical cells.
AB  - The leaves of Saussurea triangulata (Compositae) have been eaten with rice as a
      wrapping vegetable for preventing neuro-aging. However, the components
      responsible for the neuroprotective effects of S. triangulata still remain
      unidentified. In the process of investigating the neuroprotective activity of S.
      triangulata, we found that a methanol extract of S. triangulata exhibited
      significant protection against glutamate-induced toxicity in primary cultured rat
      cortical cells. Three quinic acid derivatives were isolated from the n-BuOH
      fraction of S. triangulata. Among these three quinic acid derivatives, methyl 5
      caffeoylquinic acid (3) exhibited significant neuroprotective activities against
      glutamate-induced toxicity exhibiting cell viability of about 50%, at
      concentrations ranging from 0.1 microM to 10 microM. Therefore, the
      neuroprotective effect of S. triangulata might be due to the inhibition of
      glutamate-induced toxicity by the quinic acid derivatives from S. triangulata.

PMID- 18608780
TI  - In vivo antiplasmodial activity of 11(13)-dehydroivaxillin from Carpesium ceruum.
AB  - The whole plants of Carpesium genus are used in traditional medicine as anti
      pyretic, analgesic and vermifugic, including a topical application for sores and
      inflammation. A previous study on Carpesium genus suggested that the
      antiplasmodial activity against Plasmodium falciparum was due to the existence of
      11(13)- dehydroivaxillin (DDV) from EtOAc extracts of C. ceruum (Compositae).
      Here, the antimalarial activity of DDV was evaluated against Plasmodium berghei
      in mice. The LD(50) of the compound was determined as 51.2 mg/kg, while doses of
      124 mg/kg and above were found to be lethal to mice. DDV (2, 5, 10 mg/kg/day)
      exhibited a significant blood schizontocidal activity in 4-day early infection,
      repository evaluation and in an established infection with a significant mean
      survival time comparable to that of the standard drug, chloroquine, 5 mg/kg/day.
      DDV possesses a promising antiplasmodial activity, which can be exploited in
      malaria therapy.

PMID- 18608781
TI  - The leaf extract of Siberian Crabapple (Malus baccata (Linn.) Borkh) contains
      potential fatty acid synthase inhibitors.
AB  - The present work focused on the kinetics of the inhibitory effects of the leaf
      extract of Siberian Crabapple, named Shan jingzi in China, on chicken liver fatty
      acid synthase. The results showed that this extract had much stronger inhibitory
      ability on fatty acid synthase than that from green teas described in many
      previous reports. The inhibitory ability of this extract is closely related to
      the extracting solvent, and the time of extraction was also an important
      influencing factor. The inhibitory types of this extract on diffeerent substrates
      of chicken liver fatty acid synthase, acetyl-CoA, malonyl-CoA and NADPH, were
      found to be noncompetitive, uncompetitive and mixed, respectively. The studies
      here shed a new light on the exploration for inhibitors of fatty acid synthase.

PMID- 18608782
TI  - Isolation and characterization of a novel adenosine deaminase inhibitor, IADA-7,
      from Bacillus sp. J-89.
AB  - Adenosine deaminase (ADA), an enzyme involved in purine metabolism, catalyzes the
      hydrolytic breakdown of adenosine into inosine and free ammonia. ADA regulation
      has been targeted as a potential therapeutic agent for viral infections and
      lymphoproliferative disorders. In this study, we isolated a novel ADA inhibitor
      from a culture of Bacillus sp. J-89, and evaluated its anti-proliferative
      activity on human cancer cell lines. The ADA inhibitor was deduced as a 2-N
      methyl-2,4-diazacycloheptanone by analyses of UV, IR, EI-MASS, (1)H-NMR, (13)C
      (1)H NMR, and (13)C-NMR spectroscopy, and was designated IADA-7. IADA-7 was shown
      to inhibit purified mammalian and Actinomyces ADA. IADA-7 also inhibited the
      proliferation of both Jurkat T cells (IC(50) = 15 microg/mL) and J 82 (human
      transitional-cell carcinoma, bladder) cells (IC(50) = 25 microg/mL). In Jurkat T
      cells, apoptosis with 15 microg/mL IADA-7 for 24 and 48 hours was 9 and 13%,
      respectively. These results suggest that IADA-7 can inhibit ADA activity in
      multiple species and that it may represent a good candidate as an anti-cancer
      therapeutic agent due to its demonstrated anti-proliferative activity on cancer
      cells.

PMID- 18608783
TI  - Topological descriptors in modelling antimalarial activity: N(1)-(7-chloro-4
      quinolyl)-1,4-bis(3-aminopropyl)piperazine as prototype.
AB  - The QSAR of antimalarial activity of two distinct series of N(1)-(7-chloro-4
      quinolyl)-1,4-bis(3-aminopropyl) piperazine analogues are investigated with
      DRAGON descriptors in order to rationalize their activity. Of these two series of
      compounds, one has amide characteristics and the other has amine characteristics.
      Both the analogues have shared radial centric information (ICR) as common
      modelling descriptor with increased centricity in the molecules as preferred
      feature for antimalarial activity. Apart from this, the models of amide analogues
      suggested in favor of distantly placed nitrogen(s) and unfavorable nature of
      carbonyl moieties adjacent to nitrogen in the varying portion of the molecule for
      the activity. Moreover, for these analogues, the regression models have preferred
      the lone pair electrons on heteroatoms (N and O) for purposes other than H-bonds
      for better activity. In case of amine analogues, the models suggested in favor of
      compact structural moieties in the varying parts of the molecule for improved
      activity. Also, for these analogues, hydrophobicity of the compound is an
      important factor for influencing activity. The variations in the models of amide
      and amine analogues are attributed to the characteristic functional differences
      of these analogues.

PMID- 18608784
TI  - Synthesis and biological activity of N-substituted spiro[benzoxazepine
      piperidine] Abeta-peptide production inhibitors.

PMID- 18608785
TI  - Synthesis of organometallic-based biologically active compounds: In vitro
      antibacterial, antifungal and cytotoxic properties of some sulfonamide
      incorporated ferrocences.
AB  - Sulfonamides incorporated ferrocene (SIF) have been synthesized by the
      condensation reaction of sulfonamides (sulfanilamide, sulfathiazole or
      sulfamethaxazole) with 1,1'-diacetylferrocene. The synthesized compounds (SIF(1)
      SIF(4)) have been characterized by their physical, spectral and analytical
      properties and have been screened for their in vitro antibacterial properties
      against pathogenic bacterial strains e.g., Escherichia coli, Pseudomonas
      aeruginosa, Bacillus subtilis Staphylococcus aureus and Salmonella typhi and for
      antifungal activity against Trichophyton longifusus, Candida albicans,
      Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata
      using Agar-well diffusion method. Most of the compounds showed good antibacterial
      activity whereas, all the compounds exhibited significant antifungal activity.
      Brine shrimp bioassay was also carried out for in vitro cytotoxic properties
      against Artemia salina.

PMID- 18608786
TI  - Antiplasmodial activities of sesquiterpene lactone from Carpesium cernum.
AB  - The whole plant of genus Carpesium is used in traditional medicine as an anti
      pyretic, analgesic and vermifugic, including a topical application for sores and
      inflammation. Previous experiments on Carpesium rosulatum suggested that the
      antiplasmodial effect was due to the existence of ineupatorolide A. In present
      paper, screening of Carpesium species from South Korea showed that this plant
      refers to which species had promising antiplasmodial activity. Subsequently, this
      species was selected for bioassay-guided fractionation in order to identify the
      active principles. Fractionation of the ethyl acetate extract of the whole plants
      by chromatographic techniques yielded four characterised sesquiterpenoid lactones
      which exhibited antiplasmodial activity against Plasmodium falciparum. This being
      the first time that this has been reported from Carpesium cernum. The
      antiplasmodial activity of the isolated compounds was determined against the
      Plasmodium falciparum.

PMID- 18608787
TI  - Inhibition of AChE by malathion and some structurally similar compounds.
AB  - Inhibition of bovine erythrocyte acetylcholinesterase (free and immobilized on
      controlled pore glass) by separate and simultaneous exposure to malathion and
      malathion transformation products which are generally formed during storage or
      through natural or photochemical degradation was investigated. Increasing
      concentrations of malathion, its oxidation product malaoxon, and its
      isomerisation product isomalathion inhibited free and immobilized AChE in a
      concentration-dependent manner. KI, the dissociation constant for the initial
      reversible enzyme inhibitor-complex, and k3, the first order rate constant for
      the conversion of the reversible complex into the irreversibly inhibited enzyme,
      were determined from the progressive development of inhibition produced by
      reaction of native AChE with malathion, malaoxon and isomalathion. KI values of
      1.3 x 10(-4) M(-1), 5.6 x 10(-6) M(-1) and 7.2 x 10(-6)M(-1) were obtained for
      malathion, malaoxon and isomalathion, respectively. The IC50 values for
      free/immobilized AChE, (3.7 +/- 0.2) x 10(-4) M/(1.6 +/-0.1) x 10(-4), (2.4 +/-
      0.3) x 10(-6)/(3.4 +/- 0.1) x 10(-6)M and (3.2 +/- 0.3) x 10(-6) M/(2.7 +/- 0.2)
      x 10(-6) M, were obtained from the inhibition curves induced by malathion,
      malaoxon and isomalathion, respectively. However, the products formed due to
      photoinduced degradation, phosphorodithioic O,O,S-trimethyl ester and O,O
      dimethyl thiophosphate, did not noticeably affect enzymatic activity, while
      diethyl maleate inhibited AChE activity at concentrations > 10mM. Inhibition of
      acetylcholinesterase increased with the time of exposure to malathion and its
      inhibiting by-products within the interval from 0 to 5 minutes. Through
      simultaneous exposure of the enzyme to malaoxon and isomalathion, an additive
      effect was achieved for lower concentrations of the inhibitors (in the presence
      of malaoxon/isomalathion at concentrations 2 x 10(-7) M/2 x 10(-7) M, 2 x 10(-7)
      M/3 x 10(-7)M and 2 x 10(-7) M/4.5 x 109-7) M), while an antagonistic effect was
      obtained for all higher concentrations of inhibitors. The presence of a non
      inhibitory degradation product (phosphorodithioic O,O,S-trimethyl ester) did not
      affect the inhibition efficiencies of the malathion by-products, malaoxon and
      isomalathion.

PMID- 18608788
TI  - In vitro antifungal and antibacterial activities of extracts of Galium
      tricornutum subsp. longipedunculatum.
AB  - The aim of this study was to evaluate the antimicrobial activity of crude
      ethanolic extracts and fractions of the ariel parts and the fruits of Galium
      tricornutum subsp. longipedunculatum, traditionally used in northern areas of
      Pakistan for treating microbial infections of skin. Extracts and their fractions
      were tested against six bacteria and six fungal strains using the hole diffusion
      method and macrodilution method. All extracts and fractions possessed significant
      antimicrobial effect. Four fungal strains, Candida albicans, Trichophyton
      longifusus, Fusarium.solani and Candida glabrata, showed interesting
      susceptibility profiles when evaluated using the extracts and fractions with MICs
      ranging from 0.18 to 200 mg/mL. In case of bacterial strains, Staphylococcus
      aureus, Pseudomonas aeruginosa and Salmonella typhi were significantly
      susceptible to the extracts and fractions with MICs ranging from 0.12 to 200
      mg/mL. Comparative results were carried out using imepenem, miconazole and
      amphotericin B as standard antibiotics.

PMID- 18608789
TI  - Validation of a software-based stability assessment system for   wheelchairs and
      their occupants.
AB  - Injuries relating to unstable wheelchairs are frequent and can be serious.
      Current physical tilt testing methods for wheelchairs and their occupants present
      health and safety issues for both testers and wheelchair users. In this study, a
      comparison was made between a software-based wheelchair stability assessment
      technique and physical tilting of wheelchairs on an inclined ramp. One manual and
      one powered wheelchair were studied loaded with a Hybrid II anthropometric test
      dummy. The software system's performance was assessed for both ideal clinical use
      and domiciliary use where floors may not be perfectly level. Close correlation
      was shown between the two systems for both level and unlevel floors; Pearson
      correlation coefficient 0.75 - 0.97. Repeatability was demonstrated with a
      standard deviation range of 0.18 to 0.78. In the majority of cases, the software
      assessed stability angle was less than the recorded tipping angle, reflecting a
      factor of safety.

PMID- 18608790
TI  - ECG signal processing using multiresolution analysis.
AB  - In this paper, multiresolution analysis using wavelets is discussed and evaluated
      in ECG signal processing. The approach we developed for processing the ECG
      signals uses two steps. In the first step, we implement an algorithm based on
      multiresolution analysis using discrete wavelet transform for denoising the ECG
      signals. The results we obtained on MIT-BIH ECG signals show good performance in
      denoising ECG signals. In the second step, multiresolution analysis is applied
      for QRS complex detection. It is shown that with such analysis, the QRS complex
      can be distinguished from high P or T waves, baseline drift and artefacts. The
      results we obtained on ECG signals from the MIT-BIH database show a detection
      rate of QRS complexes above 99.8% (sensitivity=99.88% and predictivity=99.89%),
      and a total detection failure of 0.24%.

PMID- 18608791
TI  - Influence of microwave-microencapsulated citric acid on some sensory properties
      of chewing gum.
AB  - Over the past few decades, microwave processing and its high potential
      capabilities have attracted food scientists. Application of microwave for
      microencapsulation is an innovative and new method in which the shell, due to
      having different dielectric constant, can fuse and cover core. In this research,
      the citric acid powder at various size ranges was microencapsulated by casein and
      inulin, using a domestic microwave oven. Then, for sensory evaluation purposes,
      they along with uncoated citric acid and commercial microcapsules were
      incorporated in chewing gum formulation. The qualitative and quantitative
      evaluations revealed the potential capability of this technique at micronized
      scales. Moreover, findings on some sensory characteristics showed practical and
      efficient applicability of inulin-coated microcapsules in chewing gum where its
      sensory scores were competitive and even much better than commercial ones. In
      addition, these observations elucidate a new approach for producing functional,
      nutritional and dietetic chewing gums.

PMID- 18608792
TI  - Three weeks release BCNU loaded hydrophilic-PLGA microspheres for interstitial
      chemotherapy: Development and activity against human glioblastoma cells.
AB  - The aim of this study is the development of microspheres of BCNU for intracranial
      administration, as an alternative to marketed novel Gliadel Implant in the
      treatment of brain tumours. H poly-lactide-co-glycolide biodegradable
      microspheres of BCNU with a mean size of 33.5 + or - 1.8 microm were obtained by
      an oil-in-water emulsion solvent evaporation method. Their small size would allow
      their intracranial administration through a needle by cerebral stereotaxia if
      tumour recurrence occurs, without a surgical intervention, as Gliadel needs. BCNU
      was released from these microspheres during 21 days, mainly by a mechanism of
      diffusion from the polymer matrix (K = 2.91 mg days(-(1/2))). The cytotoxic
      effects of these microspheres on human glioblastoma cells were demonstrated all
      through 21 days and the value of percentage of viable cells was less than 40%.
      These microspheres should be commercialized as a freeze-dried product to keep at 
      20 degrees C. Three hundred and twenty milligrams of microspheres contain 61.6 mg
      of BCNU, the same amount of BCNU contained in 1600 mg or eight wafers of Gliadel
      usually implanted after the tumour resection.

PMID- 18608793
TI  - Optimization of formulation variables for the development of long acting
      microsphere based depot injection of olanzapine.
AB  - This work was aimed to optimize the composition of microspheres of olanzapine to
      design long acting depot injection for the treatment of psychosis. Solvent
      evaporation method was used for the fabrication of microspheres. Different
      formulation variables for the solvent evaporation method, viz., effect of
      theoretical drug loading, type of surfactant and its concentration, temperature,
      volume of external phase and presence of salt in external aqueous phase,
      conditions and time of solvent evaporation and drying methodology were optimized.
      The microspheres were characterized for encapsulation efficiency, particle size,
      surface morphology, residual solvent content, drug release profile and drug
      release kinetics. The optimized formulation showed consistent drug release for
      upto 14 days time period.

PMID- 18608794
TI  - Preparation of polysulfone microcapsules containing 1-octanol for the recovery of
      caprolactam.
AB  - Polysulphone (PSF) microcapsules containing 1-octanol were prepared with solvent
      extraction method for the recovery of caprolactam. One-step and two-step
      processes were, respectively, applied to prepare microcapsules. In order to get
      high extractant loading, a loading method with the assistance of ultrasound has
      been developed. With the two-step preparation process the extractant loss can be
      avoided. A very high extractant loading ratio of 5.96 g g(-1) and the maximum
      uptake to caprolactam of 65.6 mg g(-1) were achieved. Under the action of
      ultrasound the extractant loading efficiency is greatly intensified. With the one
      step process 1-octanol loading ratio is highly limited. Only 1.74 g g(-1) loading
      ratio and 29.9 mg g(-1) uptake to caprolactam were realized. Meanwhile the
      extractant loss in the one-step process is serious. Considering extraction
      capacity and extractant loss in the preparation process, it is suggested that PSF
      microcapsules containing 1-octanol should be prepared with the two-step process.
      To fasten mass transfer rate, microcapsules with relatively smaller size are
      desired.

PMID- 18608795
TI  - Development of a novel nanocapsule formulation by emulsion-diffusion combined
      with high hydrostatic pressure.
AB  - A common method used to prepare polymeric nanoparticles in pharmaceutical
      technology is emulsion-diffusion. However, this method has several disadvantages
      due to the long duration of the process. At the diffusion step of conventional
      emulsion-diffusion, high pressure treatment could replace the addition of great
      quantities of water resulting in diffusion of the solvents from the internal
      phase to the external phase. The objective of the present study was to develop a
      novel method for nanoparticle formulation by combining high pressure treatment
      with the emulsion-diffusion method to avoid an additional diffusion step in the
      aqueous phase. After emulsification at 11,000 rpm, the emulsions were pressurized
      at 100, 200 and 300 Mpa, each for 300, 600, 900 or 1200 s. The mean size and
      morphology of the nanoparticles were analysed by Mastersizer, TEM and SEM. The
      mean size of pressurized emulsion nanoparticles was the same at 100 MPa for
      holding times up to 600 s. Also, the pressurized emulsion nanoparticle size
      increased and the peak and width of the size distribution curve was higher and
      slightly narrower depending on the pressure and the holding time. This study
      shows that pressure treatment can produce polymer membranes surrounding the oil
      surface owing to the precipitation of PCL, inducing the diffusion of solvent from
      the interior to the exterior based on TEM images. From these results, it is
      believed that high pressure treatment should be considered as a successful
      alternative for preparing nanoparticles.

PMID- 18608796
TI  - Evaluation of albumin microspheres as oral delivery system for Mycobacterium
      tuberculosis vaccines.
AB  - Mucosal immunization has been suggested to be the best option for preventing
      Mycobacterium tuberculosis infection. The purpose of this study was to develop
      albumin microspheres containing Mycobacterium tuberculosis antigens and to
      determine if oral administration of the microspheres can induce antigen-specific
      mucosal and systemic immune responses. Albumin microspheres containing
      Mycobacterium tuberculosis dead cells and cell lysate were prepared. The physico
      chemical characteristics of the formulations were determined and the microspheres
      were administered to animal models to evaluate the induction of immune responses
      to the antigens. The results showed that the particle sizes, zeta potential and
      dissolution pattern of the microspheres were ideal for oral delivery of vaccines.
      In vivo studies showed high production of antigen-specific antibody production in
      serum, nasal, salivary and faecal samples. From the results of the study, it can
      be concluded that oral administration of Mycobacterium tuberculosis microspheres
      was successful in inducing antigen-specific systemic and mucosal immune
      responses.

PMID- 18608797
TI  - Gel core liposomes: an advanced carrier for improved vaccine delivery.
AB  - Many sub-unit vaccines are successful in preventing the occurrence of disease,
      but their use is largely restrained due to low immunogenicity. Novel carrier
      based vaccine could serve as a vaccine adjuvant to overcome low immunogenicity of
      sub-unit vaccines. The use of liposomes as a delivery system for antigen is well
      recognized but they are unstable and release of antigen from them cannot be
      controlled over a prolonged period of time. To overcome the limitation of
      liposomes, this study has developed gel core liposomes in which a core of polymer
      was incorporated inside the liposomal vesicles, which serve the function of
      skeleton and provide mechanical strength to vesicles. In the present
      investigation BSA-loaded gel core liposomes were prepared by reverse phase
      evaporation method and characterized for vesicles size, shape, entrapment
      efficiency, in vitro release and stability studies. The in vivo studies to
      evaluate antigen presenting potential of the gel-core liposomes was performed in
      Balb/c mice by measuring the immune response elicited by intramuscular
      administration of BSA-loaded gel core liposomes and compared with intramuscularly
      administered BSA-loaded conventional liposomes, alum adsorbed BSA and plain
      antigen. Results indicate that intramuscular immunization with gel core liposomes
      induces efficient systemic antibody responses against BSA as compared to other
      formulations. The gel core liposomal formulation provides good entrapment
      efficiency, enhanced in vitro stability, prolonged antigen release and effective
      immunoadjuvant property, justifying its potential for improved vaccine delivery.

PMID- 18608798
TI  - Poly (epsilon-caprolactone) microparticles containing Levobunolol HCl prepared by
      a multiple emulsion (W/O/W) solvent evaporation technique: effects of some
      formulation parameters on microparticle characteristics.
AB  - The aim of this study was to prepare poly (epsilon-caprolactone) (PCL)
      microparticles of Levobunolol HC1 (L-HC1) for use as an anti-glaucomatous drug to
      the eye. The double emulsion (W/O/W) solvent evaporation technique was used for
      encapsulating L-HC1 as a hydrophilic drug. The study examined the impact of
      different factors including the pH and volume of the external aqueous phase, the
      concentration of polyvinylalcohol (PVA) and Pluronic F68 (PF68) used as
      stabilizers and drug/polymer ratios on the characteristics of the microparticles.
      Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC)
      were used to identify the physical state of the drug and polymer. The zeta
      potential of the particles was also identified. Entrapment efficiency was found
      to be highest with a 0.5% PVA concentration and 100 mL volume of external aqueous
      phase at pH 12. The high efficiency was due to a reduction in the degree of drug
      ionization. The microparticles were spherical and appropriately sized for
      ophthalmic application. Drug release from the microparticles appears to consist
      of two components, with an initial rapid release followed by a slower stage. Drug
      release was slower when the microparticle was incorporated into the thermally
      reversible gel (Pluronic F127) in comparison to drug release from the free drug
      incorporated into the gel and drug release from the free microparticle.

PMID- 18608799
TI  - Gelatin microspheres of rifampicin cross-linked with sucrose using thermal
      gelation method for the treatment of tuberculosis.
AB  - Oral controlled release microspheres of rifampicin (RIF) were prepared in order
      to circumvent the required regular high dose of the conventional dosage forms for
      the treatment of tuberculosis. Rifampicin containing microspheres were designed
      by using a biodegradable and biocompatible polymer, gelatin B, using a thermal
      gelation method. The microspheres were cross-linked with natural cross-linker,
      sucrose, to avoid the toxicities due to the synthetic di- and poly-aldehydes.
      This formulation was found to be controlled release for drug in the gastro
      intestinal tract. Drug encapsulation efficiency was found to be in the range of
      52-83%. These microspheres were characterized for; particle size analysis by
      optical microscopy and scanning electron microscopy; in vitro release study by
      USP paddle apparatus and drug polymer interaction study using DSC and FT-IR. The
      results suggested that microspheres prepared by the above method were smaller in
      size, i.e. less than 60 microm and sucrose could be used as an interesting means
      to cross-link gelatin B microspheres, allowing the use of this formulation for
      controlled release of rifampicin. Microspheres could be observed in the
      intestinal lumen at 4 h and were detectable in the intestine 24 h post-oral
      administration, although the percentage of radioactivity had significantly
      decreased (t(1/2) of (99m)Tc = 4-5 h). Dissolution and scintigraphy studies have
      shown promising results, proving the utility of the formulation for the whole
      intestine.

PMID- 18608800
TI  - Formulation, characterization and evaluation of rotavirus encapsulated PLA and
      PLGA particles for oral vaccination.
AB  - Polylactide (PLA) and polylactide-co-glycolide (PLGA) particles entrapping
      rotavirus (strain SA11) were formulated using a solvent evaporation technique. To
      minimize denaturation of viral antigen during the emulsification process, serum
      albumin was used as a stabilizer. Use of NaHCO(3) and sucrose during the primary
      emulsification step resulted in uniform stabilized particles entrapping
      rotavirus. Sonication during the primary emulsion and homogenization during the
      secondary emulsion process resulted in particles of sizes 2-8 microm, whereas
      nanoparticles were formed when sonication was used during both primary and
      secondary emulsion processes. Scanning electron and atomic force microscopy
      showed uniform pores and roughness throughout the polymer particle surface.
      Single dose oral immunization with 20 microg of antigen entrapped in PLA
      particles elicited improved and long-lasting IgA and IgG antibody titer in
      comparison to the soluble antigen. The study shows results illustrating the
      usefulness of polymeric microparticles as a potential oral delivery system for
      rotavirus vaccine.

PMID- 18608801
TI  - Effect of drying processes and curing time of chitosan-lysine semi-IPN beads on
      chlorpheniramine maleate delivery.
AB  - Beads of semi-interpenetrating polymer network (semi-IPN) have been synthesized
      from chitosan and lysine with varying amounts of glutaraldehyde solution used as
      a cross-linker. The cross-linked beads are dried by different drying processes
      such as air-drying, oven-drying and freeze-drying. These semi-IPNs are
      characterized under a scanning electron microscope (SEM). Swelling studies of
      these beads are carried out in different pH (2.0 and 7.4) solutions. The effect
      of concentration of cross-linking agent and curing period on the swelling as well
      as on the drug release is analysed. The results indicate that the size of matrix
      depend on the curing time of beads, concentration of glutaraldehyde and technique
      of drying. The freeze-dried beads exhibit a relatively higher percentage of
      swelling in the range of 66-89% as compared to oven-dried beads (53-74%) and air
      dried beads (39-61%). The drug loaded beads which are cured for different time
      intervals followed by drying are tested for in-vitro release of chlorpheniramine
      maleate (CPM) drug. The rate of drug release from freeze-dried beads is much
      faster than that from the oven-dried and air-dried beads.

PMID- 18608802
TI  - Retained integrity of protein encapsulated in spray-dried chitosan
      microparticles.
AB  - Chitosan microparticles for delivery of proteins were prepared by spray-drying
      technique. The effects of formulation (molecular weight and concentration of
      chitosan) and process variables (inlet drying air temperature and spray rate) on
      size and morphology of microparticles were characterized. Size of microparticles
      was mainly controlled by formulation variables, while particle morphology was
      influenced by both formulation and process variables investigated in this study.
      Bovine serum albumin (BSA), as a model protein, was loaded into microparticles at
      different levels. BSA-loaded chitosan microparticles were characterized in terms
      of physicochemical properties and integrity of encapsulated protein, which was
      studied by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and
      circular dichroism. Size of microparticles ranged between 3.760-8.681 microm, of
      which BSA-loaded microparticles were larger in size than their corresponding
      blank microparticles. All microparticles showed dented or distorted surface,
      especially when BSA was incorporated, with positive surface charge exposed. Burst
      release of protein was observed. The effect was more pronounced as BSA loading
      level was increased. Integrity of entrapped protein could be retained when BSA
      was incorporated at high loading level. In conclusion, chitosan microparticles
      for delivery of protein could be efficiently prepared by spray-drying technique.
      The encapsulated protein was capable of retaining its integrity after the
      preparation process.

PMID- 18608803
TI  - Ascorbic acid retaining using a new calcium alginate-Capsul based edible film.
AB  - This work aimed to produce a new calcium alginate-Capsul edible film with
      antioxidant incorporated in matrix. The vitaminic stability was evaluated in the
      films during their storage under different conditions for 140 days. The films
      were characterized with respect to their mechanical properties and surface
      morphology. The results indicated a 25.6% of vitamin C incorporation in matrix
      during the film preparation. The films stored under refrigeration in the dark did
      not show a decrease in the vitaminic retention. The films stored under room
      temperature in the dark and in the bright/dark cycles exhibited significant
      decreases in the vitamin retaining from the 84th and 70th days, respectively. The
      vitamin C addition significantly decreased the tensile strength in the new
      pellicle. The results of the microscopy revealed a cohesive matrix in the new
      edible films. These results support the utilization of the new pellicle to
      protect ingredients, although more studies are necessary.

PMID- 18608804
TI  - L-cysteine encapsulation in liposomes: effect of phospholipids nature on
      entrapment efficiency and stability.
AB  - Liposomal entrapment of L-cysteine (L-CySH) could be a solution to enhance its
      oxidative stability and its intracellular bioavailability for glutathione (GSH)
      synthesis. This study addresses the influence of different factors (i.e. pH value
      (6.3 vs 7.4), antioxidant agents (EDTA or tocopherol (TO and nature of
      phosphatidylcholine (PC) (Soybean PC (SPC) vs hydrogenated SPC (HSPC)) to
      formulate and optimize Large Unilamellar Vesicles (LUVs) of L-CySH composed of
      PC/Cholesterol/ Phosphatidylglycerol (6:3:1). pH decrease (p = 0.0002) and
      substitution of SPC by HSPC (p < 0.001) reduced L-CySH oxidation. EE% (entrapment
      efficiency) varied from 0.98% +/- 0.54 (SPC, pH 7.4) to 6.46% +/- 1.37 (HSPC, pH
      6.3) and was improved by decreasing pH (p = 0.011) and using HSPC (p < 0.0001).
      An immediate release of L-CySH was observed with SPC. On the contrary, with HSPC
      at pH 6.3, 42.0% +/- 1.2 and 73.0% +/- 1.7 remained encapsulated after 24h at 25
      degrees C and 4 degrees C, respectively. In conclusion, HSPC offering both
      stronger rigidity and lesser propensity for peroxidation led to optimize L-CySH
      liposomal stability.

PMID- 18608805
TI  - Ketoprofen-loaded Eudragit RSPO microspheres: an influence of sodium carbonate on
      in vitro drug release and surface topology.
AB  - Eudragit RSPO microspheres containing ketoprofen as model drug, prepared by
      solvent evaporation technique using acetone-liquid paraffin (heavy) solvent
      system were examined. Depending upon polymer concentration in the internal phase,
      microspheres of particle mean diameter (122.8, 213.6 and 309.5 MUm) were
      obtained. The influence of surface washing of microspheres with n-hexane, i.e.
      untreated microspheres (UM) on the drug content, drug release and surface
      topology of microspheres were compared to those of microspheres washed with
      sodium carbonate, i.e. treated microspheres (TM) in order to make the non
      encapsulated surface drug soluble. The significant reduction in encapsulation
      efficiency (p < 0.001) and drug content (p < 0.001) after treatment, in
      combination with the small crystalline peaks observed during XRD testing and lack
      of melting endotherm observed in DSC testing, suggests that the washing process
      actually removes a significant amount of drug (p < 0.001) from the surface and
      encapsulated near to the surface of the microsphere polymer matrix. Scanning
      electron microscopy (SEM) examination revealed that the removal of surface drug
      did not affect the size of microspheres but the topology of treated smallest
      microspheres was modified. The ketoprofen release profiles were examined in
      phosphate buffer pH 7.4, using USPXXIII paddle type dissolution apparatus. In
      general both UM and TM result in biphasic release patterns, but the initial burst
      effect (first release phase) of TM was lower than that of UM. The second release
      phase did not change for the bigger size but increased for the smallest
      microspheres, probably owing to the modification of matrix porosity.

PMID- 18608806
TI  - Determination of entrapment efficiency and drug phase distribution of submicron
      emulsions loaded silybin.
AB  - This paper compared the performance of ultrafiltration (UF), ultracentrifugation
      (UC) and microdialysis (MD) for determining the entrapment efficiency (EE) of
      submicron emulsions (SE) loaded with a model drug, silybin (SB). Also, a novel
      way was created to evaluate the drug phase distribution of SE. The EE of SEI,
      SEII and SEIII with a range of particle sizes (109.8, 171.7 and 213.2 nm) and the
      drug phase distribution of SEII and SEIII were separately determined by the three
      methods. The EEs of SEI were 99.8%, 91.1%, 84.4% determined by MD, UF, UC,
      respectively, and the EEs of SEII and SEIII were 99.5%, 86.4%, 72.1% and 99.4%,
      84.3%, 66.3%, separately. The accuracy of MD to determine EE of SE is much less
      than that of UF. Although UC is the fastest and most simple to use, its results
      are the least reliable. The sequence of the amount of drug in SE is as follows:
      O/W interface, aqueous phase and oil phase. Over 80% of SB was in the O/W
      interface of SEII and SEIII individually. The method created is reliable for
      quantifying the phase distribution of drug in submicron emulsions.

PMID- 18608807
TI  - Morphological and structural properties of two-phase coaxial jet electrosprayed
      BSA-PLA capsules.
AB  - Bovine serum albumin (BSA) was encapsulated with poly (lactide) (PLA) using a two
      phase coaxial jet electrospray technique in which two immiscible liquids were
      injected separately through two concentrically located and electrified capillary
      needles under a sufficiently strong electric field. BSA acted as the driving
      liquid due to its high electrical conductivity, while the high viscosity of the
      PLA and low interfacial tension of the PLA and BSA solutions favoured the
      formation of stable cone-jets. The morphology of the particles was changed from
      irregular to fully spherical with smooth surfaces when the PLA concentration
      increased from 1 to 5%. The effects of the PLA concentration and flow rate and
      applied voltage on particle size were statistically significant. Particle size
      increased as PLA concentration increased from 2 to 3.5% and decreased as the
      applied voltage was increased from 15 to 19 kV. No BSA melting peak was detected
      in DSC plot and BSA exhibited an amorphous or disordered-crystalline state in the
      PLA micoparticles, while FTIR results indicated that the secondary structure of
      the BSA was preserved.

PMID- 18608808
TI  - Development and characterization of 5-FU bearing ferritin appended solid lipid
      nanoparticles for tumour targeting.
AB  - Ferritin coupled solid lipid nanoparticles were investigated for tumour
      targeting. Solid lipid nanoparticles were prepared using HSPC, cholesterol, DSPE
      and triolien. The SLNs without ferritin which has similar lipid composition were
      used for comparison. SLNs preparations were characterized for shape, size and
      percentage entrapment. The average size of SLNs was found to be in the range 110
      152 nm and maximum drug entrapment was found to be 34.6-39.1%. In vitro drug
      release from the formulations is obeying fickian release kinetics. Cellular
      uptake and IC50 values of the formulation were determined in vitro in MDA-MB-468
      breast cancer cells. In vitro cell binding of Fr-SLN exhibits 7.7-folds higher
      binding to MDA-MB-468 breast cancer cells in comparison to plain SLNs. Ex-vivo
      cytotoxicity assay on targeted nanoparticles gave IC50 of 1.28 microM and non
      targeted nanoparticles gave IC50 of 3.56 microM. In therapeutic experiments, 5
      FU, SLNs and Fr-SLNs were administered at the dose of 10 mg 5-FU/kg body weight
      to MDA-MB-468 tumour bearing Balb/c mice. Administration of Fr-SLNs formulation
      results in effective reduction in tumour growth as compared with free 5-FU and
      plain SLNs. The result demonstrates that this delivery system possessed an
      enhanced anti-tumour activity. The results warrant further evaluation of this
      delivery system.

PMID- 18608809
TI  - Effects of encapsulated rabbit mesenchymal stem cells on ex vivo expansion of
      human umbilical cord blood hematopoietic stem/progenitor cells.
AB  - The expansion of umbilical cord blood mononuclear cells (UCB MNCs) was
      investigated in a novel co-culture system by means of encapsulation of rabbit
      bone marrow (BM) mesenchymal stem cells (MSCs) in alginate beads (Alg beads).
      Three kinds of media were applied and the experiments lasted for 7 days. The
      total nucleated cell density was measured every 24 h. Flow cytometric assay for
      CD34(+) cells and methylcellulose colony assays were carried out at 0, 72 and 168
      h. It was found that the encapsulated MSCs illustrated remarkable effects on UCB
      MNCs expansion regardless of whether serum is present in culture media or not. At
      the end of 168 h co-culture, the total nucleated cell number was multiplied by 15
      +/- 2.9 times, and CD34(+) cells 5.3 +/- 0.3 times and colony-forming units in
      culture (CFU-Cs) 5.6 +/- 1.2 times in the serum-free media supplemented with
      conventional dose of cytokines, which was very similar to the results in the
      containing 20% serum media. While in the control, i.e. MNC expansion without
      encapsulated MSCs, however, total nucleated cells density changed mildly, CD34(+)
      cells and CFU-Cs showed little effective expansion. It is demonstrated that the
      encapsulated stromal cells can support the expansion of UCB MNCs effectively
      under the experimental condition.

PMID- 18608810
TI  - Microencapsulated electric ink using gelatin/gum arabic.
AB  - Gelatin/gum arabic (GA) microcapsules were prepared by a convenient one step
      complex coacervation, in which TiO2 nanoparticles modified by stearic acid (SA)
      and homodispersed in tetrachloroethylene (TCE) were encapsulated. The modified
      TiO2 was characterized by Fourier transform infrared spectroscopy (FT-IR),
      dynamic light scattering (DLS) and optical microscopy, etc. And the effects of
      various microencapsulation parameters were also experimentally investigated. It
      was shown that SA-coated TiO2 nanoparticles are capable of subsidence-resistance
      in TCE as the SA is bonded to the surface of TiO2 nanoparticles through
      esterification. In addition, under the optimal encapsulated condition, the
      microcapsules can be prepared with regular morphology and transparent and smooth
      surface. Finally, the particles in microcapsules possessed reversible response to
      dc electric field and the response time is approximately 280 ms.

PMID- 18608811
TI  - Vesicular aceclofenac systems: a comparative study between liposomes and
      niosomes.
AB  - Vesicular delivery systems have been reported to serve as local depot for
      sustained drug release. Aceclofenac multilamellar liposomes and niosomes were
      prepared and a comparative study was done between them through evaluation of
      entrapment efficiency, particle size, shape, differential scanning calorimetry
      and in vitro drug release. A stability study was carried out by investigating the
      leakage of aceclofenac and the change in the vesicles particle size when stored
      at (2-8 degrees C) for 3 months. The anti-inflammatory effect of aceclofenac
      vesicles was assessed by the rat paw oedema technique. Results showed that the
      entrapment efficiency and the in vitro release of aceclofenac from the vesicles
      can be manipulated by varying the cholesterol content, the type of surfactant as
      well as the type of charge. Niosomes showed better stability than liposomes. Both
      vesicular systems showed significant sustained anti-inflammatory activity
      compared to the marketed product, with niosomes being superior to liposomes as
      manifested by both oedema rate and inhibition rate percentages suggesting their
      effectiveness as topical anti-inflammatory delivery systems.

PMID- 18608812
TI  - Preparation and characterization of novel semi-interpenetrating polymer network
      hydrogel microspheres of chitosan and hydroxypropyl cellulose for controlled
      release of chlorothiazide.
AB  - Novel semi-interpenetrating polymer network (IPN) hydrogel microspheres of
      chitosan (CS) and hydroxypropyl cellulose (HPC) were prepared by emulsion-cross
      linking method using glutaraldehyde (GA) as a cross-linker. Chlorothiazide (CT),
      a diuretic and anti-hypertensive drug with limited water solubility, was
      successfully encapsulated into IPN microspheres. Various formulations were
      prepared by varying the ratio of CS and HPC, percentage drug loading and amount
      of GA. Microspheres were characterized by Fourier transform infrared (FTIR)
      spectroscopy to investigate the formation of IPN structure and to confirm the
      absence of chemical interactions between drug, polymer and cross-linking agent.
      Scanning electron microscopy (SEM) was performed to study the surface morphology
      of the microspheres. SEM showed that microspheres have smooth surfaces. Particle
      size, as measured by laser light scattering technique, gave an average size
      ranging from 199-359 mum. Differential scanning calorimetry (DSC) was performed
      to know the formation of IPN structure. X-ray diffraction (X-RD) studies were
      performed to understand the crystalline nature of the drug after encapsulation
      into IPN microspheres. Encapsulation of drug up to 76% was achieved as measured
      by UV spectroscopy. Both equilibrium and dynamic swelling experiments were
      performed in 0.1 N HCl. Diffusion coefficients (D) for water transport through
      the microspheres were estimated using an empirical equation. In vitro release
      studies indicated the dependence of release rate on the extent of cross-linking,
      drug loading and the amount of HPC used to produce the microspheres; slow release
      was extended up to 12 h. The release data were also fitted to an empirical
      equation to compute the diffusional exponent (n), which indicated that the
      release followed the non-Fickian trend.

PMID- 18608813
TI  - Controlled release metformin hydrochloride microspheres of ethyl cellulose
      prepared by different methods and study on the polymer affected parameters.
AB  - The objectives of this investigation were to prepare microspheres of the anti
      diabetic drug, metformin hydrochloride, using ethyl cellulose as the polymer and
      evaluate the encapsulation efficiency and release characteristics in vitro and in
      vivo; utilizing different microencapsulation techniques. Different proportions of
      polymer were used to obtain varying drug-polymer ratios. Physical properties,
      loading efficiency and dissolution rate were dependent on the method chosen for
      preparation and also on the drug-to-polymer ratio. The addition of surfactant
      during emulsification and petroleum ether in non-solvent addition process
      affected release of drug and also size distribution of microspheres. To
      investigate the type of mechanism that occurs, dissolution data were plotted
      according to different kinetic models. In vitro release studies show first order
      and Higuchi model release characteristics being exhibited. All the results were
      treated statistically to validate the findings. Significant differences in
      percentage yield, entrapment efficiency and sustaining capacity were seen with
      microspheres prepared by two different methods. In vivo studies in normal and
      hyperglycemic mice show faster glucose reduction with microspheres prepared by
      the evaporation method, whereas the release sustaining effect was more pronounced
      with microspheres prepared by the non-solvent addition method.

PMID- 18608814
TI  - Ciclosporin-loaded poly(lactide) microparticles: effect of TPGS.
AB  - The properties of spray dried PLA microparticles were affected by the choice of
      solvents, amount of ciclosporin and TPGS added. Ethyl acetate formed
      microparticle with smooth surface when compared to those produced by
      dichloromethane. The results of FTIR have not shown chemical interaction amongst
      PLA, ciclosporin and TPGS while thermal analysis showed physical interactions
      amongst these components. TPGS was found to lower Tg value of PLA by exerting a
      plasticizing effect while ciclosporin reverted this effect. When the content of
      TPGS increased from 2% (w/w) to 10% (w/w), the microparticles tended to
      agglomerate due to the lowering of the polymer Tg values at the employed spray
      drying temperature. In addition, a lesser amount of ciclosporin was found at the
      surface of the microparticle and resulted in smaller initial release of
      ciclosporin. When 2% (w/w) TPGS was used, the initial release of ciclosporin was
      enhanced and the microparticles formed were not agglomerated.

PMID- 18608815
TI  - Post-traumatic stress disorder following childbirth: current issues and
      recommendations for future research.
AB  - BACKGROUND: An increasing body of research shows that a proportion of women
      experience significant symptoms of Post-Traumatic Stress Disorder (PTSD)
      following childbirth. AIMS AND METHOD: An international group of researchers,
      clinicians, and user-group representatives met in 2006 to discuss the research to
      date into PTSD following childbirth, issues and debates within the field, and
      recommendations for future research. This paper reports the content of four
      discussions on (1) prevalence and comorbidity, (2) screening and treatment, (3)
      diagnostic and conceptual issues, and (4) theoretical issues. CONCLUSIONS:
      Current knowledge from the perspectives of the researchers is summarized,
      dilemmas are articulated and recommendations for future research into PTSD
      following childbirth are made. In addition, methodological and conceptual issues
      are considered.

PMID- 18608816
TI  - Longitudinal study on the predictors of parental stress in mothers and fathers of
      toddlers.
AB  - AIM: Longitudinal study on the predictors of parental stress in mothers and
      fathers of toddlers. BACKGROUND: To study whether anxiety, depression, or marital
      problems increase the parenting stress in parents of toddlers. METHODS: At early
      pregnancy, 2 - 3 months, and 2 - 3 years after delivery, 214 low-risk couples
      filled in questionnaires on their marital relationship, social support, child's
      temperament, and self-evaluated competence in routine care-taking. In
      hierarchical regression analyses, they were used as predictors of parental
      stress. RESULTS: Those mothers who in early pregnancy had adequate social
      support, adaptive social strategies, and high self-esteem, and who had given
      birth vaginally, enjoyed breastfeeding, and whose spouse supported breastfeeding
      reported less stress 2 - 3 years later. Pregnancy-related anxiety, depression,
      general anxiety, neuroticism, and vulnerability in early pregnancy, as well as
      child's temperament and low self-estimated competence in routine care-taking
      measured at both 2 - 3 months and 2 - 3 years after childbirth predicted parental
      stress. Depression and living alone in early pregnancy, and the child-related
      variables (temperament and care-taking, measured both at 2 - 3 months and 2 - 3
      years after childbirth) predicted high parenting stress in fathers of toddlers.
      CONCLUSIONS: Parental stress in toddlers' parents was predicted both by the
      temperament of the child, and by the parents' depression, self-esteem, and
      anxiety, as well as by lack of support and low self-evaluated competence in
      routine care-taking.

PMID- 18608817
TI  - Maternity blues as predictor of postpartum depression: a prospective cohort study
      among Japanese women.
AB  - BACKGROUND: Maternity blues and postpartum depression are common complications of
      childbearing. However, few studies have shown the relationship between the
      severity of maternity blues and the risk of postnatal depression. We carried out
      a longitudinal study among Japanese women to show that maternity blues is a
      useful factor for predicting postpartum depression. METHODS: Two hundred and
      thirty-five women completed questionnaires before delivery, and five days, one
      month, and three months after delivery. They were required to answer the Stein's
      Blues Scale and Edinburgh Postnatal Depression Scale and other variables. A
      sequential logistic regression analysis was performed to estimate the association
      of maternity blues with postpartum depression. The stratum-specific likelihood
      ratio was then calculated. RESULTS: The prevalence of postpartum depression was
      12.8%. A Stein's Blues Scale of eight or above was significantly associated with
      postnatal depression. Likelihood ratios (95% CI ) for the Stein's Blues Scale of
      0 to 3, 4 to 7, 8 to 11 and 12 or more were 0.33 (0.16-0.65), 1.06 (0.60-1.88),
      3.42 (1.64-7.12) and 9.57 (3.41-26.86), respectively. CONCLUSIONS: These findings
      suggest that maternity blues is a strong predictor of postpartum depression. The
      higher the blues score, the higher the risk of postpartum depression.

PMID- 18608818
TI  - Premenstrual syndrome in Thai nurses.
AB  - OBJECTIVE: To investigate prevalence of premenstrual syndrome (PMS) and its
      associated factors among Thai nurses. METHODS: The study was conducted in 423
      nurses in a university hospital during October 2005 to March 2006. Prevalence of
      PMS was determined using a validated Thai version of Premenstrual Symptoms
      Screening Tool (PSST). Factors associated with PMS were analyzed using Student t
      test and Chi-square test. RESULTS: The prevalence of PMS in Thai nurses was
      25.1%. Nurses with younger age, nulligravida, lower income, more coffee
      consumption, dysmenorrhea, and negative attitude toward menstruation had higher
      prevalence of PMS. After multiple logistic regression analysis, the significant
      factors associated with PMS were coffee consumption > 1 cups/day and negative
      attitude toward menstruation; odds ratios (95% confidence interval) were 2.322
      (1.257 to 4.288) and 5.768 (2.096 to 15.872), respectively. CONCLUSION: According
      to the Thai PSST, 25.1% of Thai nurses are suffering from PMS. The significant
      associated factors were more coffee consumption and negative attitude toward
      menstruation.

PMID- 18608819
TI  - Management of chronic pelvic pain additional to tubal sterilization.
AB  - OBJECTIVE: A case series is presented to illustrate the dilemma in management of
      women with Chronic Pelvic Pain (CPP) additional to a tubal sterilization.
      METHODS: Between January 1999 and June 2007, five women consulted the Department
      of Gynecology for CPP additional to tubal sterilization with Filshie Clips (FCs).
      A biopsychosocial approach of the complaint was offered and laparoscopic removal
      of the clips was performed in all cases. The effectiveness of this management was
      assessed by a personal interview and a retrospective chart review. RESULTS: Two
      of the five patients refused an exploration of psychosocial factors possibly
      contributing to or maintaining the pain. During laparoscopic removal of the
      Filshie Clips no additional pathology was noted. At follow-up four women declared
      to have benefited from the removal procedure. CONCLUSION: If women present with
      CPP additional to sterilization with FCs in the absence of obvious pathology,
      gynecologists have to pay attention to the possibility of underlying psychosocial
      factors to this complaint. However, this attention can be in conflict with the
      woman's conviction that only removal of the clips will alleviate her pain. In
      that case, laparoscopic removal might be a component of the management.

PMID- 18608820
TI  - Psychological mood state of opiate addicted women during pregnancy and postpartum
      in comparison to non-addicted healthy women.
AB  - Opiate addiction has been widely documented to have negative impact on pregnancy
      course and outcome. Unfavorable psychosocial situation of addicted women
      predispose for poor processing of the physiological and psychological demands of
      pregnancy. Thus aim of our study was to investigate the psychological mood state
      of opiate addicts during pregnancy and postpartum in comparison to healthy women.
      In a case-controlled, prospective, longitudinal study nine pregnant opiate
      addicts and nine healthy pregnant women matched by age, level of education and
      gestational age at birth were interviewed in the third trimester of pregnancy and
      postpartum. Standardized questionnaires and inventories for assessment of the
      general psychopathology and emotional state, the perceived self-efficacy
      expectancy, the psychosocial adaptation to pregnancy and the fear of delivery,
      respectively were applied. Addicted women achieved significantly higher scores in
      the test assessing general psychopathology and emotional state before delivery
      compared to abstinent women. Interestingly this difference was unverifiable
      postpartum. This study reaffirms the presumption of a disadvantageous
      psychological condition in pregnant opiate addicts in comparison to healthy
      pregnant women for the first time in a prospective case-control study design.

PMID- 18608822
TI  - Complications during pregnancy, peri- and postnatal period in a sample of women
      with a history of child abuse.
AB  - BACKGROUND: As a proposed risk factor for infant and child development, maternal
      history of abuse has been a frequent target of investigation. However, there have
      been no controlled studies about the impact of maternal history of abuse on the
      medical course of pregnancy, the peri- and postnatal period. METHOD: All women
      with a newborn child were contacted by mail and presented with the Childhood
      Trauma Questionnaire (CTQ). The index group (n = 58) was formed by women who
      scored above the cutoff for moderate or severe abuse and compared to a control
      group (n = 60) with regard to pre,- peri-, and postnatal complications as
      documented in the patient charts. RESULTS: The results show that women with a
      history of abuse have significantly more prenatal medical complications and
      infant medical complications in the post- but not perinatal period. CONCLUSIONS:
      Maternal history of abuse significantly impacts the medical course of delivery
      and the puerperium. Given the prevalence of abusive experiences, this finding is
      highly relevant from a preventive point of view.

PMID- 18608823
TI  - Fear during labor: the impact of sexual abuse in adult life.
AB  - Our aim was to study the occurrence of extreme fear during labor and its
      association with previous sexual abuse in adult life. All postpartum women (n =
      414) in two municipalities in Norway participated in a questionnaire study. Self
      reported fear during labor was categorized as "no fear/some fear/extreme fear".
      Sexual abuse was measured by the Abuse Assessment Screen (AAS). Three percent of
      the women reported extreme fear during labor, 13% some fear and 84% no fear. In
      total, 12% had been sexually abused as an adult. Among the women with extreme
      fear during labor, however, one third had a history of sexual abuse in adult life
      (crude odds ratio 3.7; 95% CI: 1.0-3.7). When controlling for depression in
      pregnancy, duration of labor and mode of delivery, the adjusted odds ratio for
      extreme fear during labor was 4.9 (95% CI: 1.2-19.1). The results suggest that
      women with a history of sexual abuse in adult life have an increased risk of
      extreme fear during labor.

PMID- 18608824
TI  - Discussions about self-obtained samples for HPV testing as an alternative for
      cervical cancer prevention.
AB  - OBJECTIVES: Patient-collected samples for human papillomavirus (HPV) testing have
      shown promise, thus opening up a new possibility for cervical cancer screening.
      The purpose of this study was to explore women's beliefs about collecting their
      own samples for HPV testing instead of participating in conventional Pap testing.
      METHODS: Three focus groups were conducted in diverse cities in Ontario, Canada.
      One group included women from a small under-serviced northern city, one included
      culturally diverse women from a large urban city, and one included culturally
      diverse women from a medium sized under-serviced city. Transcripts were coded
      using open and axial coding as well as focused coding procedures and were
      organized using qualitative software. The Health Belief Model (HMB) was used as a
      framework for designing the focus group guide and interpreting the results.
      RESULTS: Six overriding themes were identified in the analysis: (1) need (and
      desire) for information about cervical cancer and HPV, (2) concerns about self
      sampling, (3) perceived potential of self-sampling, (4) logistics remain
      unanswered, (5) need for education and promotion of self-sampling, and (6) need
      for options. CONCLUSION: The six themes were connected to some or all of the HBM
      components. In particular, self-sampling provides a different benefits-minus
      barriers equation, which might make it a preferred screening option for some
      women.

PMID- 18608825
TI  - A controlled trial of Chinese herbal medicine for premenstrual syndrome.
AB  - Premenstrual syndrome (PMS) is a common disorder troubling many women during
      their reproductive years. The Chinese have been using herbal medicines to treat
      menstrual cycle related symptoms for centuries. The present study examined the
      effectiveness of Chinese herbal medicine for the treatment of PMS among
      Australian women within the theoretical framework of traditional Chinese medicine
      (TCM). Sixty-one women were assigned randomly into two groups within different
      TCM patterns. Herbal medicine and placebo were provided sequentially for a period
      of three months. There were significant differences (p < 0.01) in scores after
      three months of treatment between Chinese herbal medicine and placebo in
      premenstrual physical and psychological symptoms, depression, anxiety and anger
      favoring herbal medicine, but with no difference in perceived stress (p > 0.05).
      There were highly significant reductions (p < 0.001) between baseline and the end
      of the third herbal treatment month in all assessments in both groups except that
      a significant result (p < 0.05) was recorded on perceived stress only in the
      herbs-first group. No adverse effects were reported by any participant. The
      results support the hypothesis that the symptoms occurrence and severity of PMS
      can be effectively reduced by the use of Chinese herbal medicine.

PMID- 18608826
TI  - United States obstetrician-gynecologists' accuracy in the simulation of
      diagnosing anxiety disorders and depression during pregnancy.
AB  - The objective of this study was to examine obstetrician-gynecologists' diagnostic
      accuracy for mental health issues during pregnancy through utilization of
      clinical vignettes describing depressive and anxiety symptoms, as well as to
      explore factors associated with increased diagnostic accuracy and related
      practice patterns. Questionnaires were mailed to 1193 American College of
      Obstetricians and Gynecologists Fellows and Junior Fellows. The response rate was
      44% after three mailings. Depression was correctly identified by over 90% of
      respondents, whereas significantly fewer correctly diagnosed panic disorder (55%)
      and generalized anxiety disorder (32%). Confidence ratings significantly
      predicted diagnostic accuracy in some cases. Approximately half of respondents
      reported referring anxiety disordered patients to a mental health professional.
      There may be an education gap in ob-gyns' diagnostic knowledge of anxiety
      disorders, which may addressed by increasing physician confidence in diagnosis
      through increased training.

PMID- 18608827
TI  - Predicting depressive symptoms and grief after pregnancy loss.
AB  - Women who experience pregnancy loss are at high risk for depression and grief. We
      conducted a prospective cohort study to identify antenatal predictors of
      depressive symptoms and grief following pregnancy loss. Particular emphasis was
      given to the potential role of religiosity and spirituality. In multivariable
      linear regression models, depressive symptoms were significantly positively
      associated with baseline depression score and a history of mental illness.
      Depression scores were significantly inversely associated with age. Increasing
      age was also protective against post-pregnancy loss grief, as was participation
      in organized religious activities. Clinicians should be particularly alert to
      signs of depression following pregnancy loss in younger women and in women with a
      history of mental illness during or before pregnancy. The inverse association
      between religious attendance and grief following pregnancy loss merits further
      study.

PMID- 18608828
TI  - Functional impact of emotions on athletic performance: comparing the IZOF model
      and the directional perception approach.
AB  - The aim of this study was to examine the impact of emotions on athletic
      performance within the frameworks of the Individual Zones of Optimal Functioning
      (IZOF) model and the directional perception approach. Intensity, functional
      impact, and hedonic tone of trait and state anxiety, self-confidence,
      idiosyncratic emotions, and bodily symptoms were assessed in high-level Italian
      swimmers and track and field athletes (N = 56). Three standards of performance
      (poor, average, and good), derived from retrospective self-ratings across one to
      three competitions (a total of 90 observations), were used as independent
      variables in the analysis of variance of intensity, intra-individual, and
      direction scores of anxiety, self-confidence, idiosyncratic emotions, and bodily
      symptoms. Subsequently, intra-individual scores were categorized as near to or
      distant from optimal/dysfunctional zones and entered as the independent variable
      in the analysis of direction scores. The results provided support for the
      predictions stemming from both the IZOF model and the directional approach, as
      well as help in interpreting direction of anxiety and other idiosyncratic
      emotions within the IZOF framework. Athletes tended to perceive emotional levels
      approximating an individual's optimal zone as facilitative-pleasant, and
      emotional levels approximating an individual's dysfunctional zone as debilitative
      unpleasant.

PMID- 18608829
TI  - The "coherent majority average" for juries' evaluation processes.
AB  - I propose a method to synthesize the performance scores for artistic sports such
      as rhythmic gymnastics, figure skating, synchronized swimming, and diving by
      taking into account inter-judge variability, while maintaining all the reliable
      scores. This procedure is based on the assumption that the majority of the scores
      in each event are reliable and they relate well to those scores that are closest
      to them. The method consists of putting scores in order and considering clusters
      of m consecutive scores, where m is the number of judges making up the simple
      majority. For each cluster, the difference between the highest and the lowest
      score is calculated. In cases where the minimum difference is positive, the
      arithmetic mean of those scores that belong to clusters where the difference is
      minimal is computed. In cases where the minimum difference is zero (i.e. if the
      majority of judges unanimously assign the same score), then the set of the scores
      to consider within the mean is extended to those scores that are very near to
      those of the majority of the judges. A comparison between the actual evaluation
      procedures and the proposed model is provided.

PMID- 18608831
TI  - The locus of focus: the effect of switching from a preferred to a non-preferred
      focus of attention.
AB  - Focusing strategies are known to play a significant role in motor performance,
      with individuals who use an internal focus on body movement typically showing
      poorer outcomes than those who focus on features of the external environment.
      Focus of attention and switching of one's focus are examined in the context of
      two different complex motor skills along with a factor not previously examined
      systematically, individual preference. In both experiments, participants were
      introduced to focusing strategies that might be employed when attempting a
      sensorimotor task. Explanations of both strategies were given to participants.
      Specifically, for an internal focus, participants were instructed to concentrate
      on their body movements, while for an external focus, they were instructed to
      focus on aspects in the environment. They were then asked which strategy they
      preferred. Participants then continued either with their preferred focus or were
      instructed to switch to their non-preferred focus. The advantage that the
      external focus typically enjoys turns out not to be a simple one and interacts
      with individual preference and with the "forced-opposite" manipulation. Our
      results support the growing consensus that encouraging individuals to adopt an
      internal focusing strategy is counterproductive in complex sensorimotor tasks.
      They also suggest that individual preferences play a role.

PMID- 18608830
TI  - Correlations between serum and salivary hormonal concentrations in response to
      resistance exercise.
AB  - The aim of present study was to examine the relationships between serum and
      salivary values of free testosterone, dehydroepiandrosterone, and cortisol before
      and after a session of resistance exercise. Twenty-eight healthy men (mean age 40
      years, s = 4) participated in the present study. Serum and salivary samples were
      collected at rest and after a multiple-sets resistance exercise protocol, of
      approximately 25 minutes duration. Concentrations of free testosterone,
      dehydroepiandrosterone, and cortisol were measured using radioimmunoassay kits.
      No significant correlation was observed between serum free testosterone and
      salivary testosterone (r = 0.22 to 0.26, P > 0.05). Serum cortisol was
      significantly correlated with salivary cortisol before (r = 0.52, P = 0.005) and
      after (r = 0.62, P = 0.001) the exercise protocol. Serum and salivary
      concentrations of dehydroepiandrosterone were significantly correlated before (r
      = 0.68, P < 0.001) and after (r = 0.7, P < 0.001) exercise. The results of the
      present study suggest that even under exercise conditions, the salivary values of
      cortisol and dehydroepiandrosterone can reflect the behaviour of these hormones
      in blood. However, further studies are necessary to verify if salivary
      testosterone reflects the behaviour of serum free testosterone during resistance
      exercise.

PMID- 18608832
TI  - Effect of a novel pedal design on maximal power output and mechanical efficiency
      in well-trained cyclists.
AB  - In this study, we evaluated the effects of a novel pedal design, characterized by
      a downward and forward shift of the cleat fixing platform relative to the pedal
      axle, on maximal power output and mechanical efficiency in 22 well-trained
      cyclists. Maximal power output was measured during a series of short (5-s)
      intermittent sprints on an isokinetic cycle ergometer at cadences from 40 to 120
      rev min(-1). Mechanical efficiency was evaluated during a submaximal incremental
      exercise test on a bicycle ergometer using continuous VO(2) and VCO(2)
      measurement. Similar tests with conventional pedals and the novel pedals, which
      were mounted on the individual racing bike of the participant, were randomized.
      Maximal power was greater with novel pedals than with conventional pedals
      (between 6.0%, s(x) = 1.5 at 40 rev min(-1) and 1.8%, s(x) = 0.7 at 120 rev min(
      1); P = 0.01). Torque production between crank angles of 60 degrees and 150
      degrees was higher with novel pedals than with conventional pedals (P = 0.004).
      The novel pedal design did not affect whole-body VO(2) or VCO(2). Mechanical
      efficiency was greater with novel pedals than with conventional pedals (27.2%,
      s(x) = 0.9 and 25.1%, s(x) = 0.9% respectively; P = 0.047; effect size = 0.9). In
      conclusion, the novel pedals can increase maximal power output and mechanical
      efficiency in well-trained cyclists.

PMID- 18608833
TI  - No effect of glutamine supplementation and hyperoxia on oxidative metabolism and
      performance during high-intensity exercise.
AB  - Glutamine enhances the exercise-induced expansion of the tricarboxylic acid
      intermediate pool. The aim of the present study was to determine whether oral
      glutamine, alone or in combination with hyperoxia, influenced oxidative
      metabolism and cycle time-trial performance. Eight participants consumed either
      placebo or 0.125 g kg body mass(-1) of glutamine in 5 ml kg body mass(-1) placebo
      1 h before exercise in normoxic (control and glutamine respectively) or hyperoxic
      (FiO(2) = 50%; hyperoxia and hyperoxia + glutamine respectively) conditions.
      Participants then cycled for 6 min at 70% maximal oxygen uptake (VO(2max))
      immediately before completing a brief high-intensity time-trial (approximately 4
      min) during which a pre-determined volume of work was completed as fast as
      possible. The increment in pulmonary oxygen uptake during the performance test
      (DeltaVO(2max), P = 0.02) and exercise performance (control: 243 s, s(x) = 7;
      glutamine: 242 s, s(x) = 3; hyperoxia: 231 s, s(x) = 3; hyperoxia + glutamine:
      228 s, s(x) = 5; P < 0.01) were significantly improved in hyperoxic conditions.
      There was some evidence that glutamine ingestion increased DeltaVO(2max) in
      normoxia, but not hyperoxia (interaction drink/FiO(2), P = 0.04), but there was
      no main effect or impact on performance. Overall, the data show no effect of
      glutamine ingestion either alone or in combination with hyperoxia, and thus no
      limiting effect of the tricarboxylic acid intermediate pool size, on oxidative
      metabolism and performance during maximal exercise.

PMID- 18608836
TI  - Effect of time-of-day-specific strength training on maximum strength and EMG
      activity of the leg extensors in men.
AB  - In this study, we examined the effects of time-of-day-specific strength training
      on maximum strength and electromyography (EMG) of the knee extensors in men.
      After a 10-week preparatory training period (training times 17:00-19:00 h), 27
      participants were randomized into a morning (07:00-09:00 h, n = 14) and an
      evening group (17:00-19.00 h, n = 13). Both groups then underwent 10 weeks of
      time-of-day-specific training. A matched control group (n = 7) completed all
      testing but did not train. Unilateral isometric knee extension peak torque (MVC)
      and one-repetition maximum half-squat were assessed before and after the
      preparatory training and after the time-of-day-specific training at times that
      were not training-specific (between 09:00 and 16:00 h). During training-specific
      hours, peak torque and EMG during MVC and submaximum isometric contraction at 40%
      MVC were assessed before and after the time-of-day-specific training. The main
      finding was that a significant diurnal difference (P < 0.01) in peak torque
      between the 07:00 and 17:00 h tests decreased after time-of-day-specific training
      in the morning group but not in the evening or control groups. However, the
      extent of this time-of-day-specific adaptation varied between individuals.
      Electromyography during MVC did not show any time-of-day-specific adaptation,
      suggesting that peripheral rather than neural adaptations are the main source of
      temporal specificity in strength training.

PMID- 18608837
TI  - The effects of plyometric exercise on unilateral balance performance.
AB  - The purpose of this study was to determine the effects of plyometric exercise on
      unilateral balance performance. Nine healthy adults performed baseline
      measurements on the dominant limb that consisted of: a 20-s unilateral stability
      test on a tilt balance board, where a higher stability index represented
      deterioration in balance performance; isokinetic plantar flexion torque at 0.52
      and 3.14 rad s(-1); muscle soreness in the calf region; and resting plantar
      flexion angle. Plyometric exercise consisted of 200 counter-movement jumps
      designed to elicit symptoms of muscle damage, after which baseline measurements
      were repeated at 30 min, 24, 48, and 72 h. Perceived muscle soreness of the calf
      region increased significantly following the plyometric exercise protocol
      (F(4,32) = 17.24, P < 0.01). Peak torque was significantly reduced after the
      plyometric exercise protocol (F(4,32) = 7.49, P < 0.05), with greater loss of
      force at the lower angular velocity (F(4,32) = 3.46, P < 0.05), while resting
      plantar flexion angle was not significantly altered compared with baseline values
      (P > 0.05). The stability index was significantly increased (F(4,32) = 3.10, P <
      0.05) above baseline (mean 2.3, s = 0.3) at 24 h (3.3, s = 0.4), after which
      values recovered. These results indicate that there is a latent impairment of
      balance performance following a bout of plyometric exercise, which has
      implications for both the use of skill-based activities and for increased injury
      risk following high-intensity plyometric training.

PMID- 18608838
TI  - Ice friction of flared ice hockey skate blades.
AB  - In ice hockey, skating performance depends on the skill and physical conditioning
      of the players and on the characteristics of their equipment. CT Edge have
      recently designed a new skate blade that angles outward near the bottom of the
      blade. The objective of this study was to compare the frictional characteristics
      of three CT Edge blades (with blade angles of 4 degrees, 60, and 8 degrees,
      respectively) with the frictional characteristics of a standard skate blade. The
      friction coefficients of the blades were determined by measuring the deceleration
      of an aluminium test sled equipped with three test blades. The measurements were
      conducted with an initial sled speed of 1.8 m s(-1) and with a load of 53 kg on
      each blade. The friction coefficient of the standard blades was 0.0071 (s =
      0.0005). For the CT Edge blades with blade angles of 4 degrees, 6 degrees, and 8
      degrees, friction coefficients were lower by about 13%, 21%, and 22%,
      respectively. Furthermore, the friction coefficients decreased with increasing
      load. The results of this study show that widely accepted paradigms such as
      "thinner blades cause less friction" need to be revisited. New blade designs
      might also be able to reduce friction in speed skating, figure skating,
      bobsledding, and luge.

PMID- 18608840
TI  - Determination of the prevalence of anabolic steroids, stimulants, and selected
      drugs subject to doping controls among elite sport students using analytical
      chemistry.
AB  - Drug abuse by adolescents has been investigated in various surveys that reported
      correlations between age, gender, and activity. However, none of these studies
      included chemical analyses to help substantiate the statements of participants.
      In the present study, the urine specimens of 964 students (439 females, 525
      males; mean age 22.1 years, s = 1.7), who applied to study sports sciences at
      university, were assessed for anabolic steroids, stimulants, and selected drugs
      prohibited in sports. In total, 11.2% of the urine specimens provided contained
      drugs covered by doping controls. The most frequently detected compound was the
      major metabolite of tetrahydrocannabinol (9.8%) followed by various stimulants
      related to amphetamine and cocaine (1.0%). Indications of anabolic steroid use
      were found in 0.4% of urine samples but originated from contraceptives containing
      norethisterone. The present study provided unambiguous data on the status quo of
      drug (ab)use by adolescents hoping for a career related to elite sport or sports
      sciences. No use of anabolic steroids was detected. However, evidence for
      stimulants and tetrahydrocannabinol administration was obtained, although not
      reported by any participant, which highlights the issue of under-reporting in
      surveys based solely on questionnaires.

PMID- 18608841
TI  - Task complexity and sources of task-related information during the observational
      learning process.
AB  - Although research has examined the influence of various sources of task
      information for skill acquisition during observational learning, the results have
      been ambiguous. The purpose of this study was to examine sources of information
      in relation to the type of task. One hundred and twenty participants were
      randomly assigned to one of two sets of six treatment strategies: (1) all model
      demonstrations; (2) model demonstrations with physical practice with knowledge of
      performance; (3) model demonstrations with physical practice without knowledge of
      performance; (4) physical practice without knowledge of performance; (5) physical
      practice with knowledge of performance; or (6) verbal instructions only. One set
      learned a simple version of the task while the other set learned a more complex
      version. Cognitive representation and performance accuracy (spatial and temporal)
      were assessed. Results indicate that task type does influence the source of
      information to facilitate skill acquisition. The simple task benefited from model
      demonstrations, physical practice with knowledge of performance, or a combination
      of model demonstrations and practice both with and without knowledge of
      performance, while the complex version benefited more from a combination of model
      demonstrations and knowledge of performance practice. The results of this study
      provide an insight into the ambiguity that exists within the observational
      learning and motor learning literature regarding the effectiveness of information
      sources for motor skill acquisition.

PMID- 18608842
TI  - Relative age effect in Spanish association football: its extent and implications
      for wasted potential.
AB  - Spain is one of the largest and most successful powers in international youth
      football, but this success has not extended to the national team. This lack of
      continued success seems to indicate a loss of potential. The relative age effect
      has been detected in football in many countries. Understanding the extent of this
      bias in the youth teams of Spanish elite clubs may help to improve selection
      processes and reduce the waste of potential. Comparisons between players from:
      the Spanish Professional Football League, all age categories of these clubs'
      youth teams, the Under-17 to Under-21 national teams, the national team, and the
      Spanish population, show a constant tendency to under-represent players from the
      later months of the selection year at all age groups of youth and Under-17 to
      Under-21 national teams. Professional and national team players show a similar
      but diminished behaviour that weakens with ageing, which suggests that talent
      identification and selection processes can be improved to help better identify
      potential talent early on and minimize wasted potential.

PMID- 18608843
TI  - School-based prevention: effects on obesity and physical performance after 4
      years.
AB  - Juvenile obesity is increasing worldwide. Preventive strategies are warranted.
      The school-based Children's Health Interventional Trial (the CHILT Project)
      combines health education and physical activity for children. The effect on
      obesity and physical performance was studied after four years in 12 primary
      schools compared with five control schools. Anthropometric data were recorded.
      Physical performance was measured by a coordination test for children (balancing
      backwards, one-legged obstacle jumping, lateral jumping, sideways movements) and
      a 6-min run (endurance). No difference in the prevalence and incidence of
      overweight and obesity was found between the intervention and control schools
      before and after the intervention. Remission of overweight was higher in the
      intervention schools (23.2 vs. 19.2%), but not significant. An increase in
      coordination related to lateral jumping and balancing backwards was apparent in
      the intervention schools (30.6, s = 10.8 vs. 26.1, s = 10.8, P = 0.005; 21.8, s =
      11.8 vs. 19.4, s = 11.7, P = 0.007), and the increase in endurance performance
      tended to be higher in intervention schools (100.8, s = 122.7 vs. 92.8, s =
      126.0, P = 0.055), adjusted for age, sex, baseline test result, and body mass
      index at final examination. Therefore, preventive intervention in primary school
      offers the possibility to improve physical performance in children. The
      prevalence and incidence of obesity were not affected.

PMID- 18608844
TI  - Changes in swimming technique during time to exhaustion at freely chosen and
      controlled stroke rates.
AB  - The aim of this study was to assess technical changes during constrained swimming
      in time-to-exhaustion tests. Ten swimmers of national standard performed a
      maximal 400-m front crawl and two sets of exhaustion tests at 95%, 100%, and 110%
      of mean 400-m speed. In the first set (free), swimmers had to maintain their
      speeds until exhaustion and mean stroke rate was recorded for each test. In the
      second set (controlled), the same speed and individual corresponding stroke rate
      were imposed. The durations of the exhaustion tests, relative durations of the
      stroke phases, and arm coordination were analysed. For each speed in the
      "controlled" set, the exhaustion tests were shorter. Moreover, variables were
      consistent, suggesting a stabilization of stroke technique. Under the free
      condition, stroke rate increased to compensate for the decrease in stroke length.
      At the same time, swimmers reduced the relative duration of their non-propulsive
      phases in favour of the propulsive phases. Thus, swimmers changed their arm
      coordination, which came close to an opposition mode. These two constraints
      enable swimmers both to maintain their stroking characteristics and develop
      compensatory mechanisms to maintain speed. Moreover, stroke rate can be seen as a
      useful tool for controlling arm technique during paced exercise.

PMID- 18608845
TI  - Radiant heat transfer of bicycle helmets and visors.
AB  - Twenty-six bicycle helmets and their associated visors were characterized for
      radiant heat transfer using a thermal manikin headform in a climate chamber to
      assess their ability to protect the wearer from heating by the sun. A single
      configuration for applied radiant flow of 9.3 W was used to assess the roles of
      the forward and upper vents and the visor. The helmets shielded 50-75% of the
      radiant heating without a visor and 65-85% with one. Twenty-three visors were
      shown to result in a relevant reduction of radiant heating of the face (>0.5 W),
      with 15 reaching approximately 1 W. Heating of the visor and/or helmet and
      subsequent heating of the air flowing into the helmet was nevertheless found to
      be a relevant effect in many cases, suggesting that simple measures like
      reflective upper surfaces could noticeably improve the radiant heat rejection
      without changing the helmet structure. The forward vents in the helmets that
      allow the transmission of radiant heat are often important for forced convection,
      so that minimizing radiant heating geneally reduces the maximization of forced
      convective heat loss for current helmets.

PMID- 18608846
TI  - The relationships between self-assessed habitual physical activity and non
      invasive measures of cardiac autonomic modulation in young healthy volunteers.
AB  - Heart rate variability estimates cardiac autonomic modulation, but the
      relationship between habitual physical activity and heart rate variability
      remains unclear. The aims of this study were to compare RR-interval and heart
      rate variability indices in individuals of different habitual physical activity
      levels, and examine the relationship between habitual physical activity and heart
      rate variability. Ninety-two healthy volunteers (47 men, 45 women; mean age 23.1
      years, s = 2.1) were divided into tertiles according to the Baecke Questionnaire
      score. Standard heart rate variability indices were derived from 5-min resting RR
      interval recordings with paced respiration (0.25 Hz). Between-group differences
      and the relationship between habitual physical activity and heart rate
      variability were assessed. More active participants (tertiles 2-3) had longer RR
      intervals than those in tertile 1 (P < 0.05). Participants in tertile 2 had
      higher root mean squared differences of successive normal RR-intervals than those
      in tertile 1 and a higher standard deviation of normal RR-intervals than those in
      tertiles 1 and 3. There was a positive linear relationship between habitual
      activity and RR-interval. Differing RR-interval lengths were found in subgroups
      of young individuals according to level of habitual physical activity. More
      active individuals showed resting bradycardia without evidence of enhanced
      cardiac parasympathetic modulation. The mechanism linking habitual physical
      activity and RR-interval length appears to be independent of physiological
      mechanisms that can be measured by heart rate variability.

PMID- 18608847
TI  - The effect of recovery strategies on physical performance and cumulative fatigue
      in competitive basketball.
AB  - To evaluate the effectiveness of recovery strategies on physical performance
      during a 3-day tournament style basketball competition, 29 male players (mean age
      19.1 years, s= 2.1; height 1.84 m, s= 0.34; body mass 88.5 kg, s= 14.7) were
      assigned to one of three treatment groups: carbohydrate+stretching (7.7 g kg(-1)
      day(-1), s= 1.7; 'n = 9), cold water immersion (11 degrees C, 5 x 1; n = 10) or
      full leg compression garments (18 mmHg, approximately 18 h; n = 10). Effects of
      the recovery strategies on pre-post tournament performance tests were expressed
      as the mean change (% +/- standard deviation of the change score). Changes and
      differences were standardized for accumulated game time, assessed against the
      smallest worthwhile change for each test, and reported qualitatively. Accumulated
      fatigue was evident over the tournament with small to moderate impairments in
      performance tests. Sprint and agility performance decreased by 0.7% (s = 1.3) and
      2.0% (s = 1.9) respectively. Vertical jump decreased substantially after the
      first day for all treatments, and remained suppressed post-tournament. Cold water
      immersion was substantially better in maintaining 20-m acceleration with only a
      0.5% (s = 1.4) reduction in 20-m time after 3 days compared with a 3.2% (s = 1.6)
      reduction for compression. Cold water immersion (-1.4%, s = 1.7) and compression
      (-1.5%, s = 1.7) showed similar substantial benefits in maintaining line-drill
      performance over the tournament, whereas carbohydrate+stretching elicited a 0.4%
      (s =1.8) reduction. Sit-and-reach flexibility decreased for all groups, although
      cold water immersion resulted in the smallest reduction in flexibility.
      Basketball tournament play elicited small to moderate impairments in physical
      test performance. In conclusion, cold water immersion appears to promote better
      restoration of physical performance measures than carbohydrate + stretching
      routines and compression garments.

PMID- 18608848
TI  - Right impairment of temporal order judgements in dyslexic children.
AB  - This study investigates the spatial bias of visual attention measured by a
      temporal order judgement (TOJ) task and the influence of a high attentional load
      condition in a group of dyslexic children compared to a control group with normal
      reading skills (each group N=10). The TOJ task (T2) was placed after a shape
      discrimination task (T1). In a low attentional load block participants worked
      only on T2, whereas in the high attentional load block they were required to
      process both T1 and T2. Several t-tests were executed to compare performance
      between conditions and groups. In the low attentional load conditions, results in
      dyslexic children were significantly impaired for the right visual field compared
      to a control group. The high attentional load conditions did not enhance these
      effects and seems to provoke the same leftward bias in the control group.

PMID- 18608849
TI  - An fMRI study of processing novel metaphoric sentences.
AB  - Due to inconsistent findings, the role of the two cerebral hemispheres in
      processing metaphoric language is controversial. The present study examined the
      possibility that these inconsistent findings may be due, at least partly, to
      differences in the type (i.e., words vs sentences) or the familiarity of the
      linguistic material. Previous research has shown that novel two-word metaphoric
      expressions showed stronger activation in the right homologue of Wernicke's area
      for the novel metaphors than for both literal expressions and unrelated word
      pairs. In the present study fMRI was used to identify the left (LH) and the right
      hemisphere (RH) neural networks associated with processing unfamiliar, novel
      metaphoric sentences taken from poetry, as compared to those involved in
      processing familiar literal sentences and unfamiliar nonsensical sentences.
      Across participants, several left lateralised brain regions showed stronger
      activation for novel metaphoric sentences than for the nonsensical sentences
      although both types of sentence represent unfamiliar linguistic expressions.
      Moreover, the metaphoric sentences elicited more activation in the left
      dorsolateral prefrontal cortex and the posterior middle temporal gyri than did
      both the literal sentences and the nonsensical sentences. The increased
      activation in these brain regions might reflect the enhanced demand on the
      episodic and semantic memory systems in order to generate de-novo verbal semantic
      associations. The involvement of the left posterior middle temporal gyri could
      reflect extra reliance on classical brain structures devoted to sentence
      comprehension.

PMID- 18608852
TI  - Right-sided lateralisation of ovarian cancer and right bias asymmetry for
      involved pelvic lymph nodes by ovarian cancer cells.
AB  - The aim of the present study was to investigate if there is a possible
      lateralisation for ovarian cancers, to re-examine left-right asymmetry in pelvic
      lymph nodes distribution in patients with ovarian cancer, and to investigate if
      pelvic lymph node involvement by metastatic invasion of ovarian cancer cells is
      ipsilateral or contralateral. There was right-sided lateralisation for ovarian
      cancer. The numbers of external iliac and hypogastric+obturator lymph nodes were
      higher on the right side in patients with ovarian cancer on the right side; but
      they were about equal for right and left sides in patients with ovarian cancer in
      their left side. The numbers of external iliac and hypogastric+obturator lymph
      nodes involved by metastatic cancer cells were higher on the right side in
      patients with ovarian cancer on the both right and left sides. This case may
      result from the stronger cell-mediated immune activity in the left sides of
      humans.

PMID- 18608851
TI  - Mixed-handed persons are more easily persuaded and are more gullible:
      interhemispheric interaction and belief updating.
AB  - Research has shown that persons with mixed hand preference (i.e., who report
      using their non-dominant hand for at least some manual activities) display an
      increased tendency to update beliefs in response to information inconsistent with
      those beliefs. This has been interpreted as reflecting the fact that the left
      hemisphere maintains our current beliefs while the right hemisphere evaluates and
      updates those beliefs when appropriate. Belief evaluation is thus dependent on
      interhemispheric interaction, and mixed-handedness is associated with increased
      interhemispheric interaction. In Experiment 1 mixed-handers exhibited higher
      levels of persuasion in a standard attitude-change paradigm, while in Experiment
      2 mixed-handers exhibited higher levels of gullibility as measured by the Barnum
      Effect.

PMID- 18608853
TI  - Colour knowledge: the role of the right hemisphere in colour processing and
      object colour knowledge.
AB  - The lateralisation of colour processing is not well understood, although there is
      a reasonable amount of evidence indicating a right hemisphere bias for colour
      processing. Tasks that require colour naming are associated with a left
      hemisphere bias and it is likely that asymmetry of colour processing is
      influenced by task demands. It is not known whether object colour knowledge is
      lateralised. In the current study colour and achromatic Mondrian-like objects
      were presented to either the left or right hemisphere to assess the
      lateralisation of colour processing. Participants were required to judge whether
      the objects were colour or achromatic. To assess colour knowledge, congruently
      and incongruently coloured familiar objects were presented to either the left or
      right hemisphere and participants were required to judge whether the objects were
      correctly or incorrectly coloured. The data show that both colour processing and
      colour knowledge are associated with a right hemisphere bias.

PMID- 18608854
TI  - Right-left discrimination is related to the right hemisphere.
AB  - We aimed to determine the functional localisation of right-left discrimination
      (RLD) by functional MRI (fMRI). In this study, 16 male volunteers were examined.
      There were three task sessions: one active and two baseline tasks. During the
      baseline tasks participants were instructed to show numbers with their fingers.
      The first baseline task was performed with the right hand, the second one with
      the left hand. During the active (RLD) task participants were also instructed to
      show numbers. The difference between baseline and active tasks was that during
      the active task the hand with which the participant should perform the
      instruction was assigned randomly. Thus, participants were unaware which hand
      should be used before the instruction command. During RLD, activations occurred
      in the right-sided frontal, precuneus, postcentral, angular, lingual, and
      superior temporal gyri. Activations also appeared in the left-sided temporal gyri
      and precuneus. Of the activations, 76.7% appeared in the right hemisphere, 23.3%
      in the left hemisphere. Conclusively, we found that RLD is mainly related to the
      right hemisphere, and requires activation of the parieto-temporo-occipital
      junction and the visual system including cuneus, precuneus, and gyrus lingualis.

PMID- 18608855
TI  - Does a continuous measure of handedness predict reading processes and reading
      related skills across the lifespan?
AB  - The purpose of this research was to investigate the relationship between
      handedness, reading skills, and reading-related cognitive processes. Although
      lateralised differences in brain functioning are well known, research regarding
      handedness, specific reading skills, and reading-related cognitive processes is
      ambiguous at best because handedness is often measured as a dichotomous variable
      rather than a continuous variable. This methodological difference contributes to
      the diverse research findings, therefore the present investigation addressed
      these methodological limitations. A large normative sample of up to 1383
      participants who ranged in age from 4 to 80 completed the Woodcock Johnson Psycho
      Educational Battery-Revised (Woodcock & Johnson, 1989a, 1989b) or the Woodcock
      Johnson Psycho-Educational Battery-Third Edition (Woodcock, McGrew, & Mather,
      2001) in combination with the Dean Woodcock Sensory Motor Battery (Dean &
      Woodcock, 2003) lateral preference scale, a continuous measure of handedness.
      Polynomial multiple regression analyses indicated curvilinear relationships
      between handedness and reading skills, along with handedness and auditory working
      memory. Individuals towards the extremes of the handedness continuum performed
      less well on the reading-related tasks. Therefore, just knowing a general
      classification of right, left, or mixed handed will not provide significant
      knowledge regarding lateralisation or potential cognitive and academic
      consequences but rather knowledge of an individual's hand preference on a
      continuum may well be useful for evaluative purposes.

PMID- 18608856
TI  - Digit ratio (2D:4D) in individuals with intellectual disability: investigating
      the role of testosterone in the establishment of cerebral lateralisation.
AB  - It has been proposed that the ratio of the second to fourth digits (2D:4D) may be
      a proxy of prenatal androgen exposure, such that low 2D:4D ratio is associated
      with high prenatal androgen exposure. The aim of the present study was to measure
      the 2D:4D ratio in 100 right- and non-right-handed individuals with intellectual
      disability of unknown idiopathic origin and compare them to a control group of 85
      typically developing individuals. We also sought to determine whether sexually
      dimorphic traits, such as 2D:4D ratio, tend to be more pronounced on the right
      hand of these groups than on the left. Our results indicated that males had lower
      2D:4D ratios than females in both groups, and individuals with intellectual
      disability had higher ratios only in their right hand compared to typically
      developing individuals. Further, right-handed individuals had lower ratios in
      both hands compared to non-right-handed individuals. Our results are discussed in
      relation to the "Geschwind-Behan-Galaburda theory of cerebral lateralisation" and
      Witelson's callosal hypothesis that differential levels of prenatal testosterone
      exposure will cause atypical cerebral laterality in individuals with intellectual
      disability, and the suggestion that this atypicality will become evident in the
      2D:4D ratio (Manning, Scutt, Wilson, & Lewis-Jones, 1998).

PMID- 18608857
TI  - The relationship of movement time to hand-foot laterality patterns.
AB  - Asymmetries in movement times of the hands in 60 healthy participants with
      different patterns of hand-foot dominance were investigated. Handedness and
      footedness were assessed by means of questionnaires and verified by simple motor
      tasks. Psychomotor performance was evaluated by the use of selected tests from
      the computerised Vienna Test System (VST, Vienna, Austria). Movement time (MT)
      was assessed separately for dominant and non-dominant hands in a unimanual simple
      reaction task. Participants performed significantly better with their preferred
      hand, and differences in performance between right- and left-handers were not
      significant, neither was there a main effect of foot dominance on MT of the
      hands. However there was a significant effect of laterality pattern in hand-foot
      combination on hands MT: participants with cross-lateral dominance patterns of
      hands and feet performed significantly better than those with congruent hand-foot
      dominance. No significant interaction with sex was found. These results provide
      evidence for a lack of independence of hand and foot dominance in motor
      performance, suggesting the functional significance of limb laterality pattern in
      the motor control system. The results support the hypothesis that the quality of
      human hand movements may be influenced not only by central information processing
      (hemispheric specialisation) but also by other structures and processes of motor
      control, such as central pattern generators (CPGs) and biomechanical factors.

PMID- 18608859
TI  - Treatment of relapsed and refractory myeloma.
AB  - Multiple myeloma is a malignancy of plasma cells that remains incurable and
      almost all patients will eventually require some form of salvage therapy.
      Increasing insight into the biology of myeloma and the availability of new
      therapeutic options has resulted in rapid change in its management. Clinical
      trials have investigated numerous agents and regimens for the treatment of
      patients with relapsed/refractory myeloma, presenting a host of treatment
      options. Important questions in determining optimal therapy for patients with
      relapsed/refractory myeloma include the influence of prior therapy, optimal
      sequencing of regimens, sequential versus combination use of agents, and the role
      of cytogenetic and other prognostic factors. This article reviews the literature
      for the treatment of relapsed/refractory myeloma and considers the ability of the
      evidence to answer these questions, both for established regimens and newer
      regimens incorporating thalidomide, bortezomib and lenalidomide.

PMID- 18608860
TI  - Successful use of semi-nested PCR for the diagnosis of primary intraocular
      lymphoma.

PMID- 18608861
TI  - Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in
      leukemic cells through a combinatorial approach.
AB  - Delta(9)-Tetrahydrocannabinol (THC) is the active metabolite of cannabis, which
      has demonstrable cytotoxic activity in vitro. In support of our previously
      published data, we have investigated the interactions between THC and anti
      leukemia therapies and studied the role of the signalling pathways in mediating
      these effects. Results showed clear synergistic interactions between THC and the
      cytotoxic agents in leukemic cells. Additionally, exposure of cells to sub lethal
      levels of THC (1 microM) sensitised cells to these cytotoxic agents, by reducing
      IC(50) values by approximately 50%. Sensitisation appeared to be dependent upon
      the ability of THC to down regulate phosphorylated ERK, as cells dominantly
      expressive of MEK were not sensitised to the cytotoxic drugs by equi-molar
      amounts of THC. Overall, these results demonstrate for the first time that a
      combination approach with THC and established cytotoxic agents may enhance cell
      death in vitro. Additionally the MAPK/ERK pathway appears responsible in part for
      these effects.

PMID- 18608862
TI  - The difference between pre-B cell acute lymphoblastic leukemia and Burkitt
      lymphoma in relation to DNA damage repair gene polymorphisms in childhood.

PMID- 18608863
TI  - Case 38: central nervous system lymphoma in a patient previously treated for
      Wegener's granulomatosis.
AB  - A 72-year-old woman with a past history of Wegener's granulomatosis presented
      with a primary central nervous system lymphoma; this was found to be an Epstein
      Barr virus-positive diffuse large B-cell lymphoma.

PMID- 18608864
TI  - A simulated case of chronic myeloid leukemia: the growing risk of Munchausen's
      syndrome by internet.

PMID- 18608865
TI  - Serum level of soluble human leukocyte antigen-G molecules in non-Hodgkin
      lymphoma: does it have a prognostic value?

PMID- 18608866
TI  - Dasatinib-induced acute hepatitis.

PMID- 18608867
TI  - Case 39: an elderly man with red cell aplasia.
AB  - An elderly man presented with a macrocytic anemia with severe reticulocytopenia.
      The observation of trilineage dysplasia in addition to red cell aplasia led to a
      diagnosis.

PMID- 18608868
TI  - The rare t(6;8) (q27;p11) translocation in a case of chronic myeloid neoplasm
      mimicking polycythemia vera.

PMID- 18608869
TI  - Intravesical Bacillus Calmette-Guerin for the treatment of superficial bladder
      cancer following hematopoietic stem cell transplantation.

PMID- 18608870
TI  - Development of EBV-associated diffuse large B-cell lymphoma in Waldenstrom
      macroglobulinemia and mantle cell lymphoma.

PMID- 18608871
TI  - The role of non-steroidal anti-inflammatory drugs in the risk of development and
      treatment of hematologic malignancies.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) comprise the group of structurally
      diverse but similarly acting compounds that are used for relieving signs and
      symptoms of inflammation, especially in treatment of rheumatic diseases. Recent
      reports suggested potential association between regular use of NSAIDs and the
      risk of development of hematological malignancies. However, the data distinctly
      differ depending on type of NSAID used, period of its administration and type of
      malignancy. Regular use of aspirin and other NSAIDs was shown to correlate with
      reduced risk of lymphoid malignancies. Frequent use of aspirin was found to be
      associated with decreased risk of acute leukemia (AL) development. In contrast,
      correlation between long-term acetaminophen usage and increased incidence of AL
      and multiple myeloma (MM) was indicated. On the other hand, NSAIDs were found to
      exert anti-cancer effects, inhibiting proliferation and invasive growth or
      inducing cell apoptosis in several tumors, including hematologic malignancies.
      One of those agents, non-cyclooxygenase 2-inhibiting R-enantiomer of etodolac
      (SDX-101), exerts cytotoxic effects against chronic lymphocytic leukemia (CLL)
      and MM cells, and is currently investigated in phase II clinical trial in CLL.
      The indole-pyran analogue of SDX-101, SDX-308 (CEP-18082), showed more potent
      cytotoxicity than SDX-101 against MM cells and inhibited osteoclast formation and
      activity of mature osteoclasts. Thus, SDX-308 may be an ideal agent for bone
      disease in MM and related diseases. Another analogue of SDX-101, SDX-309, showed
      also significant anti-tumor activity in first preclinical studies. The potential
      role of NSAIDs in prevention and treatment of hematologic malignancies is the
      subject of this review.

PMID- 18608872
TI  - The role of high-dose chemotherapy followed by peripheral blood stem cell
      transplantation for the treatment of multiple myeloma.
AB  - The management of multiple myeloma has changed significantly over the past 10
      years. The results obtained with conventional chemotherapy were disappointing;
      however the use of high dose therapy (HDT) and stem cell transplantation has
      significantly improved survival. Autologous, allogeneic and tandem
      transplantation, along with different conditioning regimens, have been studied in
      an attempt to optimise and further improve outcomes. This review summarises the
      role of stem cell transplantation in multiple myeloma. The advent of novel
      therapies such as thalidomide, lenalidomide and bortezomib have started to
      redefine the role of peripheral stem cell transplantation, however, further study
      is needed to better understand how to most effectively use these agents in
      multiple myeloma in conjunction with HDT.

PMID- 18608873
TI  - Cardiac morbidity following modern treatment for Hodgkin lymphoma: supra-additive
      cardiotoxicity of doxorubicin and radiation therapy.
AB  - Age- and sex-specific estimates of the rate of cardiac morbidity among Hodgkin
      lymphoma (HL) patients treated with doxorubicin-based chemotherapy and radiation
      therapy (RT) are scarce. We evaluated the risk of hospital admission for cardiac
      disease in 615 HL patients, adjusting for age, sex, treatment, cardiac risk
      factors and competing causes of death. Compared with the general population, the
      risk of cardiac morbidity was highest among patients treated with both
      doxorubicin and mediastinal RT (HR = 2.77, p < 0.0001). Mediastinal RT without
      chemotherapy also significantly increased the risk (HR = 1.82, p = 0.038). For
      females and males treated with doxorubicin plus mediastinal RT at age 40, the
      estimated 15-year incidence rate of cardiac hospitalisation were 7.3% and 16.5%,
      respectively, rates 5-15% higher than expected. These results suggest that the
      risk of clinically important cardiac toxicity following HL treatment that
      includes both doxorubicin and mediastinal RT may be greater than that reported in
      prior studies of patients treated with RT alone.

PMID- 18608874
TI  - Motor control of speaking rate and oral diadochokinesis in hearing-impaired Farsi
      speakers.
AB  - Although speech motor control has been studied intensively in normal-hearing and
      hearing-impaired (HI) speakers in America and Europe, essentially no research has
      been performed using Persian-speaking participants. A total of 46 prelingual
      hearing-impaired 15-18-year-old males and 15 normally hearing control
      participants from Iran participated in the study. Three speaking performance
      measures, oral diadochokinesis (DDK), speaking rate (words per minute), and
      intelligibility ratings, were obtained for the two groups and compared to
      previously published research for English-speaking participants. The DDK results
      in general showed that the normal-hearing group produced the fastest syllable
      rates, and the profoundly HI group produced the slowest. Similar results were
      obtained for speaking rates. Speech intelligibility was highest in the normal
      hearing group and lowest in the profoundly HI group. Correlation analysis between
      DDK and speaking rates showed that for HI group only, a slow speaking rate
      corresponded to slow DDK rates. It is shown that generally there are significant
      differences in measures of speech motor control in normal-hearing and hearing
      impaired participants. These results concord with those from other language
      groups.

PMID- 18608875
TI  - Vocal fold mucus aggregation in vocally normal speakers.
AB  - Vocal fold mucus aggregation is common in persons with voice disorders. The
      normality of vocal fold mucus aggregation in vocally normal speakers is not
      known. The purpose of this study was to preliminarily ascertain the presence,
      type, thickness, location, and pooling of mucus aggregation in vocally normal
      speakers. An additional aim was to evaluate whether the features of mucus
      aggregation are more easily identified using stroboscopy or high-speed
      videoendoscopy (HSV). These aims were accomplished by visually rating a
      systematically collected database of stroboscopy and HSV recordings from 52
      normophonic speakers. Results revealed 97% of normophonic speakers presented with
      visible mucus aggregation. Statistically significant differences were found for
      judgments of HSV compared to stroboscopy on the parameters of type 1 mucus, not
      apparent and mild thickness, not apparent pooling, and all three locations. Two
      main conclusions can be drawn from this study: (1) normophonic speakers commonly
      have mucus aggregation and (2) mucus aggregation is identified more often through
      stroboscopy than HSV.

PMID- 18608876
TI  - The pharyngoesophageal segment in laryngectomees--videoradiographic, acoustic,
      and voice quality perceptual data.
AB  - This study aimed to relate the results of physiological measurements of the
      pharyngoesophageal (PE) segment in subjects using tracheoesophageal (TE) or
      esophageal (E) speech with perceptual assessment of the speakers' voice quality
      and acoustic measurements of the voice function. It further aimed to investigate
      possible differences in appearance and placement of the voice source between TE
      and E speakers. Nine subjects who had undergone a laryngectomy (five TE speakers
      and four E speakers) participated in the study. They were videoradiographically
      examined during phonation and silence. Measurements were made of size and
      placement of the PE segment, the distance between the PE segment and the anterior
      wall, and the distance between the posterior and anterior esophageal walls
      beneath the segment. Five trained listeners perceptually assessed the subjects'
      voice quality, and acoustical analyses of fundamental frequency and sound
      pressure level were made. The physiological measurements of the nine subjects'
      individual PE segments varied in terms of appearance and placement during both
      phonation and silence, but all of the subjects showed a good closure at the PE
      segment level during phonation. Statistically significant results were found
      between all of the physiological measurements of the PE segment. Significant
      results were also found between the acoustical and perceptual assessments of the
      subjects' voices. No relations were found between the physiological measurements
      and the acoustic and perceptual results. The conclusion of this study was that
      there were no specified differences in the PE segment between TE speakers and E
      speakers, but that there were large individual differences within each speaker
      group.

PMID- 18608877
TI  - A methodological contribution to the assessment of nonword repetition-a
      comparison between children with specific language impairment and hearing
      impaired children with hearing aids or cochlear implants.
AB  - Poor nonword repetition is considered as a clinical marker of specific language
      impairment (SLI). In children with expressive language problems, the analysis and
      scoring procedures are often insufficiently described. We argue for a combined
      analysis of segmental and suprasegmental accuracy in nonword repetition tasks as
      well as an appreciation of gender differences. The view is taken based on
      empirical findings in a comparison between children with specific language
      impairment, children with mild/moderate hearing impairment and hearing aids (HI),
      and children with severe to profound hearing impairment with cochlear implants
      (CI). With age and gender taken into consideration, the main effects of both
      group and syllable level on a combined measure of segmental and suprasegmental
      accuracy remained. Although not necessarily an index of limited working memory
      capacity, persistently poor imitation of nonwords might be an indication of
      language impairment in children with mild/moderate HI and in children with CI.

PMID- 18608878
TI  - Specific language impairment in childhood is associated with impaired mental and
      social well-being in adulthood.
AB  - To study the possible influence of childhood language impairment on adult life
      and well-being, 35 persons with a mean age of 34 years filled out two
      questionnaires. Compared with the general population, subjects more often lived
      with parents, and were pensioned. Only a few reported having literacy problems,
      but over 40% had difficulty in finding words and remembering instructions.
      Childhood performance IQ was associated with education and word-finding
      difficulties, and verbal IQ with difficulties in remembering instructions. Health
      related quality of life was related to literacy skills, finding words, and
      remembering instructions. In conclusion, adults with childhood language
      impairment differ markedly from the general population. Problems in expressing
      themselves and receiving information affect their well-being the most. Childhood
      performance seems to have some prognostic value for language-based problems in
      adulthood.

PMID- 18608880
TI  - Process and product in writing--a methodological contribution to the assessment
      of written narratives in 8-12-year-old Swedish children using ScriptLog.
AB  - Twenty-seven children, with typical language development (TLD), 8-10 years old
      and 10-12 years old, were assessed with keystroke-logging in order to investigate
      their narrative writing. Measures of the writing process and the written product
      were used. One purpose was to explore how children produce written narratives in
      on-line production, and to relate the writing process to the written product. The
      results showed that those children who produced the final text faster, also wrote
      stories that comprised of more words. In the group of older children, children
      with better narrative ability used less pause time than those with worse ability,
      and the girls were faster writers than the boys. We believe that keystroke
      logging gives valuable information for the assessment of young children's writing
      and that it is a potentially valid assessment tool for children from about 10
      years of age.

PMID- 18608881
TI  - Word sequence production in cognitive decline: forward ever, backward never.
AB  - Backward recall of automatic word sequences involves declarative and working
      memory abilities known to be impaired in the early stages of cognitive decline.
      Yet its utility in the diagnosis of mild cognitive impairment and mild dementia
      has not been studied in detail. We analysed word sequence production in 234
      participants drawn from three categories: subjective cognitive impairment, mild
      cognitive impairment, and mild dementia in Alzheimer's disease. The names of the
      months were used as a diagnostic target for investigating forward versus backward
      sequence production. Forward production remained normal across categories. In
      contrast, backward speed was significantly decreased in mild cognitive
      impairment. In dementia both speed and accuracy were impaired. Backward
      production had significant diagnostic classificatory power. We conclude that word
      sequence production yields data relevant to the diagnosis of dementia with a
      minimum of time and expense.

PMID- 18608882
TI  - Cladophialophora bantiana: a rare cause of fungal brain abscess. Clinical aspects
      and new therapeutic options.
AB  - Black molds or dematiaceous fungi are rare etiologic agents of intracerebral
      abscesses and such infections carry a high mortality of up to 70% despite
      combined surgical and antifungal therapy. While the growing use of
      immunosuppressive therapies and organ transplantation have caused an increase in
      the incidence of rare fungal cerebral infections, occurrence in immunocompetent
      hosts is also possible. We describe a 60-year-old female patient with a cerebral
      abscess caused by Cladophialophora bantiana. The case illustrates the clinical
      and radiological similarities between glioblastomas and brain abscesses and
      emphasizes the need to perform histological and microbiological studies prior to
      the initiation of any form of therapy. Long-term survival from cerebral black
      mold abscesses has been reported only when complete surgical resection was
      possible. The recommended antifungal treatment involves the use of amphotericin B
      combined with a triazole and, if possible, flucytosine. Highly-active new
      generation triazole antifungal compounds (voriconazole or posaconazole) are
      likely to offer improved survival rates for patients with rare mold infections.
      In particular, posaconazole could be a new therapeutic option given its better
      tolerance, lower toxicity and fewer drug-drug interactions. We discuss clinical,
      microbiological and practical pharmacological aspects and review current and
      evolving treatment options.

PMID- 18608883
TI  - Changes in frequency of agents of tinea capitis in school children from Western
      China suggest slow migration rates in dermatophytes.
AB  - Tinea capitis is a common dermatophyte infection of the scalp of children in
      Western China, with the gray-patch from being the most prevalent. Twenty years
      ago, the most widespread etiologic agent was reported to be Trichophyton
      violaceum, which was later succeeded by Microsporum ferrugineum and Trichophyton
      schoenleinii. In the framework of our recent study, 97 isolates were collected
      from patients with clinically suspected tinea capitis. Identification was
      performed by conventional methods and by sequencing the ribosomal DNA internal
      transcribed spacer region. In the case of T. violaceum an additional
      microsatellite primer set (T1) was used. Five species (in order of frequency,
      Trichophyton violaceum, T. schoenleinii, Microsporum ferrugineum, zoophilic
      strains of Arthroderma vanbreuseghemii, and Trichophyton tonsurans) were
      identified. Results of molecular and phenotypic ID of the same strains showed
      good correspondence. Comparison with earlier data showed that dermatophytes
      species in former rural societies must have migrated extremely slowly.
      Preponderance of local transmission from domesticated animals was proven by the
      occurrence of zoophilic strains of Arthroderma vanbreuseghemii. Etiologic agents
      in the rural communities of Western China tend to be different from those of the
      other regions in the country, despite modern communication and traffic.

PMID- 18608884
TI  - A new genotype of Arthroderma benhamiae.
AB  - Nucleotide sequence analysis of chitin synthase 1 (CHS1) indicated 90% sequence
      similarities among human and animal isolates of Arthroderma benhamiae. In
      particular, greater than 99% similarity was noted in the nucleotide sequence
      among Americano-European race isolates, African race isolates, and five isolates
      from four-toed hedgehogs (Atelerix albiventris). The phylogenetic analysis
      indicated that the five isolates from hedgehogs were included in the same cluster
      and distinct from the Americano-European and the African race standard strains of
      A. benhamiae. These results were confirmed by ITS analysis. Therefore, it was
      proposed that genotypes could be established for the isolates of A. benhamiae in
      association with the mating behavior.

PMID- 18608885
TI  - In vitro activity of CAY-1, a saponin from Capsicum frutescens, against
      Microsporum and Trichophyton species.
AB  - Dermatomycoses are among the world's most common diseases and their incidence has
      increased over recent years, particularly in immunosuppressed patients. In
      previous studies, the saponin CAY-1 from cayenne pepper (Capsicum frutescens),
      has shown antifungal activities against Candida albicans and Aspergillus spp. We
      therefore studied the in vitro antifungal activity of CAY-1 against non
      germinating conidia and hyphae of clinical isolates of the dermatophytes
      Trichophyton mentagrophytes, T. rubrum, T. tonsurans and Microsporum canis. We
      used a microdilution method to assess the growth inhibitory activities of CAY-1
      against conidia (CLSI document M38-A) and a colorimetric procedure (XTT method)
      to investigate the metabolic inhibitory activity of CAY-1 against hyphae. The
      minimal inhibitory concentrations (complete visual growth inhibition) of CAY-1
      against non-germinating conidia ranged from 10-20 microg/ml for all dermatophyte
      isolates included in this investigation. In addition, we found >90% inhibition of
      hyphal metabolic activity of these same isolates with 10-20 microg/ml of CAY-1.
      Results indicate that CAY-1 merits further investigation as a potential agent for
      the treatment of dermatomycoses.

PMID- 18608886
TI  - Afyap1, encoding a bZip transcriptional factor of Aspergillus fumigatus,
      contributes to oxidative stress response but is not essential to the virulence of
      this pathogen in mice immunosuppressed by cyclophosphamide and triamcinolone.
AB  - Aspergillus fumigatus, an important human fungal pathogen, encounters high levels
      of reactive oxygen species following its ingestion by phagocytes. Reactive oxygen
      species are important mediators of the fungicidal activities of phagocytes. In
      yeasts, YAP1 encodes for transcriptional factors that contribute to their
      oxidative stress response and given the importance of the stress response, we
      hypothesized that the YAP1 homologue in A. fumigatus plays a similar role in this
      fungus. In this study, we found that Afyap1, the Yap1 homologue of A. fumigatus,
      confers protection against oxidative stress. Replacement of Afyap1 with the
      marker gene pyrG (DeltaAfyap1) resulted in hypersensitivity of A. fumigatus to
      oxidants such as H(2)O(2) and menadione. In contrast, an A. fumigatus strain
      harboring multiple-copy Afyap1 was resistant to these two oxidants as well as the
      oxidant diamide. However, DeltaAfyap1 and strain harboring multiple-copy Afyap1
      were comparable in their virulence to a wild-type A. fumigatus strain in a murine
      model of invasive pulmonary aspergillosis. Taken together, these results
      demonstrate that Afyap1 is involved in oxidative stress response but is not an
      essential virulence factor for A. fumigatus.

PMID- 18608887
TI  - The emergence of Trichophyton tonsurans in Port-au-Prince, Haiti.
AB  - The occurrence of the anthropophilic dermatophyte Trichophyton tonsurans as a
      frequent causative agent of tinea capitis in several developed countries has been
      associated with a global rise in its isolation during recent years. While T.
      tonsurans was never found in Haiti before 1988, a sharp increase in the number of
      isolates of this species from scalp lesions began to be observed in 2005 in Port
      au-Prince, Haiti. A prospective study was conducted in Port-au-Prince from May to
      November 2006 of 64 children presenting with tinea capitis at the dermatological
      outpatient clinic of the university hospital. Forty-five (70%) were male and 19
      female (30%), with an average age at presentation of 6.1 years (age range 1-16
      years). Direct microscopic examination of scalp hair using 10% potassium
      hydroxide was positive in 93.8% and culture confirmation was established in 55
      cases (85.9%). Five species of dermatophytes were identified, with the
      anthropophilic dermatophyte T. tonsurans, accounting for the majority or 35
      (63.6%) of all cases of tinea capitis. Other dermatophyte species identified
      included T. mentagrophytes (14.5%), Microsporum audouinii (12.7%), T. rubrum
      (7.3%) and in one case, the geophilic M. gypseum (1.8%). In two cases caused by
      T. tonsurans skin involvement on other areas of the body was recorded. The most
      frequent pathogen in tinea capitis is now T. tonsurans in Port-au-Prince. We
      speculate that the recent emergence of T. tonsurans in Haiti is linked to the
      dramatically increasing mobility of Haitian Diaspora.

PMID- 18608889
TI  - In vitro interaction of terbinafine with itraconazole and amphotericin B against
      fungi causing chromoblastomycosis in China.
AB  - The combined effects of terbinafine with itraconazole and amphotericin B against
      Cladophialophora carrionii, Phialophora verrucosa and Fonsecaea pedrosoi were
      evaluated in vitro by the checker-board method and expressed as a fractional
      inhibitory concentration (FIC) index. Synergy was observed with the combination
      of terbinafine and itraconazole against one isolate of C. carrionii and no
      antagonism was observed. When amphotericin B was combined with terbinafine or
      itraconazole, no synergy or antagonism was noted with all isolates included in
      this investigation.

PMID- 18608888
TI  - A novel immunocompetent murine model for Candida albicans-promoted oral
      epithelial dysplasia.
AB  - Candida albicans is a common opportunistic pathogen found in the oral mucosa.
      Clinical observations indicate a significant positive association between oral
      Candida carriage or infection and oral epithelial dysplasia/neoplasia. The aim of
      this study was to test whether C. albicans is able to promote epithelial
      dysplasia or carcinoma in a mouse model of infection where a carcinogen (4
      Nitroquinoline 1-oxide [4NQO]) was used as initiator of neoplasia. Mice were
      divided into four groups: group 1 received 4NQO alone; group 2 received 4NQO
      followed by C. albicans (ATCC 90234); group 3 received vehicle dimethyl sulfoxide
      (DMSO) followed by C. albicans and group 4 was untreated. Although 4NQO treated
      mice did not develop oral lesions, mice exposed to both 4NQO and C. albicans
      developed oral dysplastic lesions 19 weeks after exposure to 4NQO. Mice
      challenged with C. albicans only developed hyperplastic lesions. The expression
      of Ki-67 and p16, two cell-cycle associated proteins that are frequently
      deregulated in oral dysplasia/neoplasia, was also tested in these lesions. Ki-67
      and p16 expression increased from normal to hyperplastic to dysplastic mucosa and
      was highest in the group exposed to both 4NQO and C. albicans. In conclusion, we
      showed that C. albicans plays a role in the promotion of oral dysplasia in a
      mouse model of infection when 4NQO was used as initiator of oral neoplasia.

PMID- 18608890
TI  - Immune dysfunction in Atlantic bottlenose dolphins (Tursiops truncatus) with
      lobomycosis.
AB  - Lobomycosis (Lacaziosis) occurs only in humans and dolphins under natural
      conditions. We evaluated the immune status of eight dolphins with lobomycosis and
      40 healthy dolphins from the Indian River Lagoon (IRL), Florida. Lobomycosis
      cases had multiple abnormalities in their immunologic parameters when compared to
      healthy dolphins. The absolute number of circulating lymphocytes and serum
      albumin concentration were reduced (P<0.05) while the segmented neutrophils,
      alpha 1, total beta, total gamma and total globulins were increased (P<0.05).
      Although innate immunity was relatively intact and phagocytosis and natural
      killer cell activity were not affected, the plasma lysozyme concentrations were
      elevated in dolphins with lobomycosis (P<0.05). Adaptive immunity was depressed
      with statistically significant decreases found in the absolute numbers of CD4(+)
      helper T cells and CD19(+) and CD21(+) B cells. The ratios of CD2(+) T cells to
      CD4(+) cells and CD2(+) to CD21(+) cells were increased (P=0.05 and P<0.05,
      respectively) and the numbers of lymphocytes expressing MHC class II molecules
      was decreased in dolphins with lobomycosis (P<0.05). Lymphocyte proliferation was
      reduced in response to stimulation with lipopolysaccharide and concanavalin A
      (P<0.05). Antibody titers to Erysipelas rhusiopathiae, a common marine micro
      organism, were decreased (P<0.05). In summary, dolphins with lobomycosis exhibit
      significant impairment in adaptive immunity.

PMID- 18608891
TI  - Diagnostic value of morphological, physiological and biochemical tests in
      distinguishing Trichophyton rubrum from Trichophyton mentagrophytes complex.
AB  - The two most frequently encountered dermatophyte etiologic agents of glabrous
      skin and nail dermatophytoses are Trichophyton rubrum and T. mentagrophytes. This
      study was aimed to discuss the efficacy of morphological, physiological and
      biochemical diagnostic tests commonly used in the identification of T. rubrum and
      members of the T. mentagrophytes complex. In this study, we evaluated; hydrolysis
      of urea in broth and on urea agar slants and Petri plates incubated at 22 degrees
      C, 28 degrees C and 37 degrees C, in vitro hair perforation (blond child, sheep
      and goat hair), pigment production on cornmeal dextrose agar (CMDA) and
      bromcresol purple-milk solids-glucose agar (BCP-MS-G), Tween opacity, sorbitol
      assimilation, and salt tolerance. Additionally, the production of micro- and
      macroconidia was investigated by using brain heart infusion agar (BHIA),
      Christensen's urea agar in Petri plates (UPA), CMDA, Lowenstein-Jensen agar
      (LJA), malt extract agar, oatmeal agar, Oxoid chromogenic Candida agar, and
      potato dextrose agar. All cultures were incubated at 28 degrees C, and conidial
      production was compared on days 5, 10 and 15. It was found that the urea
      hydrolysis test yielded more rapid and significant results when urea medium was
      prepared in Petri plates and incubated at 28 degrees C (P<0.01). LJA supported
      the highest production of microconidia after 15 days (P<0.001). Additionally, it
      was found that T. rubrum strains produced red pigment on CMDA (P<0.01) and BCP-MS
      G, while strains of the T. mentagrophytes species complex did not. A special
      algorithm containing the various test procedures employed in these studies is
      presented which was found to be useful in the differentiation of T. rubrum
      strains from T. mentagrophytes complex. Our results revealed that UPA, CMDA, BCP
      MS-G, LJA, and BHIA may be used as common mycological agars in routine practice.

PMID- 18608892
TI  - Isolation and some properties of a glycoprotein of 70 kDa (Gp70) from the cell
      wall of Sporothrix schenckii involved in fungal adherence to dermal extracellular
      matrix.
AB  - Sporothrix schenckii is the etiological agent of sporotrichosis, a subcutaneous
      mycosis and an emerging disease in immunocompromised patients. Adherence to
      target cells is a prerequisite for fungal dissemination and systemic
      complications. However, information on the cell surface components involved in
      this interaction is rather scarce. In this investigation, the extraction of
      isolated cell walls from the yeast phase of S. schenckii with SDS and separation
      of proteins by SDS-PAGE led to the identification of a periodic acid-Schiff (PAS)
      reacting 70 kDa glycoprotein (Gp70) that was purified by elution from
      electrophoresis gels. The purified glycopeptide exhibited a pI of 4.1 and about
      5.7% of its molecular mass was contributed by N-linked glycans with no evidence
      for O-linked oligosaccharides. Confocal analysis of immunofluorescence assays
      with polyclonal antibodies directed towards Gp70 revealed a rather uniform
      distribution of the antigen at the cell surface with no distinguishable
      differences among three different isolates. Localization of Gp70 at the cell
      surface was confirmed by immunogold staining. Gp70 seems specific for S.
      schenckii as no immunoreaction was observed in SDS-extracts from other pathogenic
      and non-pathogenic fungi. Yeast cells of the fungus abundantly adhered to the
      dermis of mouse tails and the anti-Gp70 serum reduced this process in a
      concentration-dependent manner. Results are discussed in terms of the potential
      role of Gp70 in the host-pathogen interaction.

PMID- 18608893
TI  - Canine sino-nasal aspergillosis: parallels with human disease.
AB  - Canine sino-nasal aspergillosis (SNA) is characterized by the formation of a
      superficial mucosal fungal plaque within the nasal cavity and/or frontal sinus of
      systemically healthy dogs. The most common causative agent is Aspergillus
      fumigatus. The fungus does not invade beneath the level of mucosal epithelium but
      incites a severe chronic inflammatory response that leads to local destruction of
      nasal bone. These clinicopathological features are equivalent to those of human
      chronic erosive non-invasive fungal sinusitis. The clinical diagnosis of canine
      SNA relies on multiple modalities but local instillation of anti-fungal agents is
      an effective therapy with high cure-rate. Recent studies have investigated the
      immunopathogenesis of canine SNA. The mucosal inflammatory infiltrate involves a
      mixture of CD4+ and CD8+ T lymphocytes, IgG+ plasma cells and activated
      macrophages and dendritic cells expressing class II molecules of the major
      histocompatibility complex. There is active recruitment of blood monocytes and
      neutrophils. Real-time quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) analysis of mucosal tissue samples has revealed up-regulation
      of Th1 (IL-12, IL-18 and IFN-gamma), Th17-related (IL-23) and pro-inflammatory
      (IL-6, TNF-alpha) cytokine mRNA with evidence of expression of genes encoding
      monocyte chemoattractant proteins 1-4. Additionally, there is significant
      transcription of the IL-10 gene consistent with local immunosuppression that
      prevents secondary immune-mediated sequelae whilst permitting chronicity of the
      infection. The source of this IL-10 may be a T regulatory population or a Th1
      population that switches phenotype during the course of disease. This
      understanding of the immunopathogenesis of canine SNA establishes this disorder
      as a valuable model for the equivalent human pathology.

PMID- 18608894
TI  - Cerebral phaeohyphomycosis caused by Scytalidium dimidiatum: a case report from
      India.
AB  - We report a case of cerebral phaeohyphomycosis caused by Scytalidium dimidiatum
      (synanamorph Nattrassia mangiferae) in a young, apparently immunocompetent Indian
      male. Etiological diagnosis was made by recovery of the fungus in culture and
      histopathological examination. The infection proved fatal despite aggressive
      antifungal therapy.

PMID- 18608895
TI  - The expanding host tree species spectrum of Cryptococcus gattii and Cryptococcus
      neoformans and their isolations from surrounding soil in India.
AB  - This study reports the widespread prevalence of Cryptococcus neoformans and
      Cryptococcus gattii in decayed wood inside trunk hollows of 14 species
      representing 12 families of trees and from soil near the base of various host
      trees from Delhi and several places in the Indian states of Uttar Pradesh,
      Haryana, Tamil Nadu and Chandigarh Union Territory. Of the 311 trees from which
      samples were obtained, 64 (20.5%) were found to contain strains of the C.
      neoformans species complex. The number of trees positive for C. neoformans var
      grubii (serotypeA) was 51 (16.3%), for C. gattii (serotype B) 24 (7.7%) and for
      both C. neoformans and C. gattii 11 (3.5%). The overall prevalence of C.
      neoformans species complex in decayed wood samples was 19.9% (111/556). There was
      no obvious correlation between the prevalence of these two yeast species and the
      species of host trees. The data on prevalence of C. gattii (24%) and C.
      neoformans (26%) in soil around the base of some host trees indicated that soil
      is another important ecologic niche for these two Cryptococcus species in India.
      Among our sampled tree species, eight and six were recorded for the first time as
      hosts for C. neoformans var grubii and C. gattii, respectively. A longitudinal
      surveillance of 8 host tree species over 0.7 to 2.5 years indicated long term
      colonization of Polyalthia longifolia, Mimusops elengi and Manilkara hexandra
      trees by C. gattii and/or C. neoformans. The mating type was determined for 153
      of the isolates, including 98 strains of serotype A and 55 of serotype B and all
      proved to be mating type alpha (MAT alpha). Our observations document the rapidly
      expanding spectrum of host tree species for C. gattii and C. neoformans and
      indicate that decayed woods of many tree species are potentially suitable
      ecological niches for both pathogens.

PMID- 18608897
TI  - A case of invasive rhinosinusitis by Fusarium verticillioides (Saccardo)
      Nirenberg in an apparently immunocompetent patient.
AB  - A case of chronic invasive rhinosinusitis in an apparently healthy man, caused by
      Fusarium verticillioides, is described. The identity of the isolate as F.
      verticillioides was established by demonstrating characteristic morphological
      features and by amplification of rDNA using species-specific primers. Surgical
      debridement of the infected nasal tissue and therapy with amphotericin B resulted
      in a favorable outcome. To the best of our knowledge, F. verticillioides has not
      been described previously to cause this condition.

PMID- 18608899
TI  - Fusarium keratitis and contact lens wear: facts and speculations.
AB  - Over the past several decades mycotic keratitis has been considered a rare sequel
      to hydrogel contact lens wear. In 2005--2006 an upswing in the incidence of
      Fusarium keratitis was associated with a disproportionate use of one multipurpose
      contact lens solution (MPS, ReNu with MoistureLoc, Bausch & Lomb, Rochester, NY).
      The MPS, as manufactured and marketed, was sterile and met regulatory guidelines
      for antimicrobial activity. A multivariant interaction of poor hygienic practices
      and the contact lens paraphernalia were associated with a mostly selective
      contamination in or on the lens storage case by members of the F. solani/F.
      oxysporum species complexes from the environment of the user. A decline of the
      anti-fusaria properties of the MPS in the lens case appeared related to its
      dissociation from drying, or dilution and the potential for sorption of
      antimicrobial solution components (e.g., alexidine) to various hydrogel lenses.
      These factors and capacities of the fusaria for rapid amplification by microcycle
      conidiation, production of dormant resistant cells, and potential for attachment
      and penetration of hydrogel lenses, were linked to the occasional selective
      fungal survival and growth during storage of the lens in MPS. Lack of a manual
      rubbing-cleaning step in the MPS disinfection process was considered a risk
      factor for keratitis.

PMID- 18608900
TI  - The loss of parts of chromosome 7 followed by the insertion of URA cassette into
      RB2 on MRS in Candida albicans strain CAI-4.
AB  - Clinical isolates of the medically important fungus Candida albicans show
      electrophoretic karyotype variations. Chromosome translocation is considered to
      be one of the possible mechanisms of karyotype variation and has been shown to
      occur very frequently at or near the unique repeated DNA sequences which comprise
      the Major Repeat Sequence (MRS) on the genome. The MRS consists of the repeated
      sequences RB2, RPS, and HOK. We previously showed the insertion at the RB2 region
      might initiate chromosome translocation in strain STN22u2 of C. albicans. To ask
      whether the insertion of a URA cassette into the RB2 but not into RPS and HOK
      causes chromosome translocation in C. albicans strains, we transformed three URA
      cassettes into strain CAI-4, which is commonly used as a host strain for gene
      knockout experiments. We found chromosome rearrangements followed the insertion
      of URA cassettes into RB2 in strain CAI-4. Three transformants had an extra
      chromosome showing the loss of the 7A and 7C region from one chromosome 7
      homologue. The recombination occurred at or after the insertion of URA cassette
      into RB2. Insertion there seems to cause chromosome rearrangement and thus RB2 is
      considered one of the important elements for initiation of chromosome
      rearrangement.

PMID- 18608901
TI  - Sexual structures in Aspergillus: morphology, importance and genomics.
AB  - The genus Aspergillus comprises a few hundred species sharing a common asexual
      spore forming structure, the aspergillum. Approximately one-third of these
      species also produce a sexual stage, all but five of which are known to be
      homothallic. Sexual stages associated with Aspergillus fall into approximately
      ten different genera, reflecting a tremendous degree of phylogenetic and
      biological diversity. Sexual stages in Aspergillus are plectomycetous, typical
      for the order in which it resides, the Eurotiales. Theoretically, a homothallic
      Aspergillus species can produce both asexual conidia and sexual ascospores in
      both clonal and recombinant fashion, although the actual significance of these
      potential modes of reproduction is unclear. Aspergillus species with known sexual
      stages tend to be minor players in infections of humans, perhaps because of their
      tendency to produce fewer asexual spores compared to their non-teleomorphic
      congeners. The discovery of population genetic and genomic evidence for sex in
      species with no known sexual stage indicates that no assumptions can be made
      about the clonal versus recombinant life histories of a species based on its
      known mitotic and/or meiotic reproductive modes.

PMID- 18608902
TI  - Molecular diagnostic platforms for detecting Aspergillus.
AB  - Invasive aspergillosis remains difficult to diagnose despite advances in imaging
      and antigen-based serological testing. To overcome this problem, nucleic acid
      (NA)-based amplification assays were introduced to identify infecting pathogens.
      Unfortunately, the reliability of such assays to detect Aspergillus spp. has met
      with mixed success. A new generation of NA platforms are emerging, which greatly
      improve our ability to detect Aspergillus-specific DNA and RNA from respiratory
      and blood samples. These platforms can accurately detect a single genome, and the
      emergence of pan-fungal and pan-Aspergillus probes offer promise for broader
      detection. PCR remains the most important platform, especially when coupled with
      real-time probes. It is multiplex friendly and can distinguish between closely
      related target sequences. Nucleic acid sequence-based amplification (NASBA) is an
      RNA-directed isothermal transcription-based amplification platform, which is more
      robust than PCR resulting in a 10(14)-fold amplification. RNA-based detection
      facilitates more target options and can be used to assess cell viability. Both
      DNA and RNA amplification platforms take advantage of allele-specific properties
      of probes, which are valuable for assessing drug resistance markers. Finally, as
      new molecular diagnostic platforms mature, their role may expand to include early
      monitoring of therapy.

PMID- 18608903
TI  - Asteroid body in sporotrichosis. Yeast viability and biological significance
      within the host immune response.
AB  - The asteroid body in Sporotrichosis (AB) is a characteristic structure that
      allows diagnosis in lymphangitic presentations and whose generation and
      composition is not fully understood. Our study focused on the biological
      relationship between the yeast and host elements present in the AB. Indirect
      immunofluorescence showed that on ABs obtained from naturally infected
      individuals there were antigenically related IgG and IgM molecules in the spikes
      of the radiated crowns. However, there were differences in the pattern of
      distribution for each immunoglobulin isotypes. The yeast cells located at the
      center of the ABs were viable, as shown by the generation of germ tubes and
      conidial formation after 36-48 hours of incubation at 22 degrees C. The central
      yeast could divide and proliferate even in the ABs that had been pre-treated with
      specific anti-Sporothrix schenckii serum and fresh complement. The data suggests
      that AB in sporotrichosis might be a resistance structure which uses the host
      immune molecules to the advantage of the yeast.

PMID- 18608906
TI  - Seborrheic dermatitis flare in a Dutch male due to commensal Malassezia furfur
      overgrowth.
AB  - This is a case of seborrheic dermatitis (SD) barbae from which Malassezia furfur
      (M. furfur) was isolated. The patient was a 57-year-old Dutch male, who was
      hospitalized for fever and weakness of extremities. He presented with symmetrical
      erythema with an abundance of greasy chaffy scales on his beard area. No reasons
      were detected for his fever following a routine search. M. furfur was identified
      through mycological examination, including direct microscopic examination,
      culture, Tween test, esculine splitting test and DNA sequencing, of samples from
      the skin lesions. The patient was treated with oral itraconazole capsules (200
      mg, b.i.d. for 8 days, then 200 mg o.d. for 13 days), washing his scalp and face
      with 2% ketoconazole shampoo (once a day) and topical application of a cream
      containing 1% naftifine hydrochloride and 0.25% ketoconazole (b.i.d.). After
      treatment the fever subsided and the SD lesion gradually healed. M. furfur was
      not isolated again from skin scrapings and 7 days later therapy was terminated
      and no recurrence was noted after one week follow-up since the cessation of
      treatment.

PMID- 18608907
TI  - Indoleamine 2,3-dioxygenase (IDO) in inflammation and allergy to Aspergillus.
AB  - Innate responses combine with adaptive immunity to generate the most effective
      form of resistance against Aspergillus fumigatus. A complex set of signaling
      networks initiate both innate and adaptive immunity in response to the different
      fungal morphotypes. In response, the fungus has developed or acquired
      sophisticated mechanisms to avoid, counteract and subvert sensors, signaling
      networks and a range of effector functions that constitute the host immune
      response. Host response and fungal countermeasures may contribute to the balance
      of pro-inflammatory and anti-inflammatory signaling that is eventually required
      to benefit both parties. Here we highlight the important contribution of the
      enzyme IDO (indoleamine 2,3-dioxygenase) and tryptophan catabolites to such a
      homeostatic condition in Aspergillus infection and allergy. By providing the host
      with immune defense mechanisms adequate for protection, without necessarily
      eliminating the fungus or causing an unacceptable level of tissue damage, IDO and
      tryptophan metabolites may prove to be potent regulators capable of taming innate
      and adaptive pathogenic inflammatory host responses.

PMID- 18608908
TI  - What do we know about the role of gliotoxin in the pathobiology of Aspergillus
      fumigatus?
AB  - Gliotoxin is a member of the epipolythiodioxopiperazine class of toxins and is
      both the major and the most potent toxin produced by Aspergillus fumigatus. Since
      the discovery of the putative gliotoxin biosynthetic 12-gene cluster in the
      genome of A. fumigatus, five different laboratories have attempted to determine
      the role of this toxin in the virulence of A. fumigatus. The genes in the cluster
      that have been disrupted to study the pathobiological importance of gliotoxin
      include gliZ that encodes a transcription factor and gliP that encodes a
      nonribosomal peptide synthase. Two of the five laboratories have reported
      gliotoxin to be an important virulence determinant of A. fumigatus, while the
      other three laboratories have shown it to be unimportant. Comparisons of the data
      generated among the five laboratories revealed that the immunosuppressive regimen
      used for mice was the key factor that contributed to the observed disparity.
      Regardless of either the mouse strains used or the route of infection,
      immunosuppression with a combination of cyclophosphamide and corticosteroids
      (neutropenic mice) showed gliotoxin to be unimportant. The mice immunosuppressed
      with corticosteroids alone, however, revealed that gliotoxin is an important
      virulence determinant of A. fumigatus. These studies indicate that the
      neutropenic mice model is inadequate to reveal the pathobiological importance of
      fungal secondary metabolites in invasive pulmonary aspergillosis.

PMID- 18608910
TI  - Persistent pulmonary infection with an azole-resistant Coccidioides species.
AB  - We report a case of a life-threatening, recurrent, and azole-resistant pulmonary
      coccidioidomycosis in a patient receiving long-term fluconazole therapy for a
      history of coccidioidal meningitis. Since this diagnosis, the patient has
      received weekly amphotericin B for more than four years and remains in remission
      with a stable serum Coccidioides complement fixation antibody titer.

PMID- 18608912
TI  - Antibody responses to Cryptococcus neoformans in Indian patients with
      cryptococcosis.
AB  - An important element of the host response to cryptococcosis is humoral immunity.
      Specific antibody responses in patients with cryptococcosis however, have not
      been extensively studied. We analyzed the antibody responses of 22 Indian
      patients with cryptococcosis, including both HIV+ and HIV- individuals. Sera from
      10 Indian patients with AIDS and without cryptococcosis were studied as controls.
      Antibody responses to cryptococcal proteins were detected by immunoblot, while
      antibodies to glucuronoxylomannan (GXM), the main component of the cryptococcal
      capsular polysaccharide were measured by ELISA. Our results indicate that
      cryptococcosis elicits antibodies to a specific pattern of cytoplasmic proteins.
      Further, we find that antibody responses to both cytoplasmic proteins and GXM are
      less robust in HIV+ patients when compared with HIV- patients.

PMID- 18608916
TI  - Gastrointestinal zygomycosis due to Rhizopus microsporus var. rhizopodiformis as
      a manifestation of chronic granulomatous disease.
AB  - A case of gastrointestinal zygomycosis in a 10-month-old boy with chronic
      granulomatous disease (CGD) is presented. Zygomycetes are an uncommon cause of
      fungal disease in CGD patients and gastrointestinal zygomycosis has not been
      previously described in individuals with CGD. To improve outcome, a timely and
      correct diagnosis is of utmost importance.

PMID- 18608917
TI  - Deficiency of IL-12p40 subunit determines severe paracoccidioidomycosis in mice.
AB  - Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by
      the thermally dimorphic fungus Paracoccidioides brasiliensis. To investigate the
      role of interleukin (IL)-12 in this disease, IL-12p40-/- deficient mice (IL-12p40
      /-) and wild type mice (WT) were infected intravenously with viable yeast cells
      of P. brasiliensis 18 isolate. We found that, unlike WT mice, IL-12p40-/- mice
      did not control fungal proliferation and dissemination and succumbed to infection
      by day 21 after inoculation. Additionally, IL-12p40-/- mice presented a higher
      number of granulomas/mm2 in lung tissue than WT mice, and showed unorganized
      granulomas containing high numbers of yeast cells. Moreover, IL-12p40-/- mice did
      not release detectable levels of IFN-gamma, but they produced high levels of IL
      10, as well as IgG1 antibody. Additionally, splenocytes from both infected IL
      12p40-/- and WT mice exhibited a suppressed Con-A-induced T cell proliferative
      response. Our findings suggest that the IL-12p40 subunit mediates resistance in
      paracoccidioidomycosis by inducting IFN-gamma production and a Th1 immune
      response.

PMID- 18608918
TI  - Three isolations of Chaetomium globosum from erythematous epilation of canine
      skin.
AB  - Chaetomium globosum is commonly found in natural environments worldwide and is
      known to be a causative agent for emerging fungal infections. The present study
      describes a case of erythematous epilation of a dog caused by C. globosum. A
      mixed-breed young dog, a 4-months-old male, weighing 7.25 kg, showed depilation,
      scales, and dermatitis with slightly itchiness on his skin. The main symptom was
      an erythematous epilation on the left subocular skin 7.5 cm in diameter,
      accompanied by elephantiasis-like hyperplasia and scales. Similar lesions were
      observed on the skin on both sides of the ear lobes, the heels, tail, and left
      angulus oris. The scales from the crusted lesion were cultured on
      chrolamphenicole-added potato dextrose agar plates at the first visit, as well as
      followed by ambulatory practices. The isolates at the first visit, 1 and 3 weeks
      after treatment, were identified as C. globosum by mycological study and the
      D1/D2 domain of the large subunit rRNA gene sequence. The patient dog was treated
      by ketoconzole both orally and externally. The lesions were cured, showing new
      hair growth 9 weeks later. In addition, the susceptibilities to antifungal agents
      for the present C. globosum isolate were as follows: amphotericin B, 4.0
      microg/ml; 5-FC 64.0 microg/ml; itraconazole, 0.5 microg/ml; miconazole, 1.0
      microg/ml; fulconazole, 16.0 microg/ml; ketoconazole, 0.25 microg/ml; and
      micafungin, 16.0 microg/ml.

PMID- 18608919
TI  - Genetic diversity among clinical Coccidioides spp. isolates in Arizona.
AB  - Increasing coccidioidomycosis rates in Arizona may indicate the development of a
      hypervirulent strain. One hundred and twenty-one clinical Coccidioides spp.
      isolates were collected over 16 months from Maricopa, Graham, Yuma, and Pima
      counties in Arizona. The patient age distribution ranged from 9 to 91 years, with
      a median age of 58 years; 36% were female, and 64% male. All isolates were
      analyzed by measuring length polymorphisms in nine distinct microsatellite
      regions. The three microsatellites found to have the greatest discriminatory
      power for Coccidioides posadasii were: K03 (0.87), GA37 (0.83), and K01 (0.78).
      The majority of isolates (n=119) were C. posadasii. Duplicate isolates (n=28)
      from 13 patients showed single strain infections. Phylogenetic analysis of the
      microsatellite data showed no dominant microsatellite pattern. We conclude that
      the increase in reported cases of coccidioidomycosis in Arizona is not linked to
      a dominant, hypervirulent strain of Coccidioides posadasii.

PMID- 18608920
TI  - Large-scale screening of the in vitro susceptibility of Prototheca zopfii towards
      polyene antibiotics.
AB  - A large scale screening of the in vitro susceptibility of 105 strains of
      Prototheca zopfii to a panel of polyene antibiotics (amphotericin B, nystatin,
      primaricin and filipin) was conducted. Strains studied were isolated from dairy
      associated environments in five different localities. Groups 1-4 included strains
      recovered from four separate regions of Italy, while group 5 included isolates
      from Belgium. Amphotericin B and primaricin exhibited the highest activity, with
      th MIC90 ranging from 4 and 8 microg/ml, respectively. On the other hand, the
      MIC90 of nystatin and filipin were from two to four times higher. Two strains
      were resistant to all four polyenes tested. The above results are compared with
      those in the literature and the importance of carrying out large-scale screening
      surveys to assess polyene susceptibility patterns within the species P. zopfii is
      discussed.

PMID- 18608923
TI  - Mitochondrial haplotypes and recombination in Candida albicans.
AB  - Candida albicans is a common commensal and opportunistic pathogenic fungus.
      Although it normally reproduces clonally, several lines of evidence exist for
      genetic recombination and some form of sexual reproduction. We have sequenced
      seven regions of its mitochondrial genome in 36 strains and constructed
      haplotypes for the 66 polymorphic sites, which include single-nucleotide
      polymorphisms and insertion/deletions. Nineteen different haplotypes were
      observed. Strains with the same mitochondrial haplotype were found in different
      clades defined by nuclear multilocus sequence typing (MLST) and the UPGMA
      dendrograms constructed using either set of data were different in topology.
      There was no apparent correlation between mitochondrial haplotype and the source
      of the strain (geographical or anatomical). Examination of the mitochondrial
      haplotypes revealed substantial evidence for recombination between polymorphic
      sites. This suggests that the use of mitochondrial haplotypes in phylogenetic
      studies should be approached with caution. These results provide further evidence
      for recombination and genetic exchange in the biology of C. albicans.

PMID- 18608924
TI  - Dectin-1 and its role in antifungal immunity.
AB  - The innate recognition of fungal pathogens is mediated by a variety of pattern
      recognition receptors (PRRs), although much interest has focussed on the Toll
      like Receptors (TLR). More recently, however, there is growing appreciation that
      the non-TLRs have a major role in the control of infection with these organisms.
      One such molecule is Dectin-1, a C-type lectin-like receptor which induces
      numerous cellular responses upon recognition of fungal beta-glucans. Here we
      review our current understanding of the functions of Dectin-1 and the underlying
      molecular mechanisms, as well as explore the role of this receptor in antifungal
      immunity.

PMID- 18608925
TI  - Regulation of immunity in bronchiectasis.
AB  - Bronchiectasis is a chronic, progressive lung disease where there is
      irreversible, abnormal dilatation of one or more bronchi, with chronic airway
      inflammation, associated chronic cough and sputum production, recurrent chest
      infections, and airflow obstruction. As such it is essentially a pathological
      endpoint with several underlying causes. Allergic bronchopulmonary aspergillosis
      (ABPA) is an important cause of bronchiectasis and aspergillus related lung
      disease sometimes complicates established bronchiectasis. A diagnosis of
      bronchiectasis is made clinically and confirmed with high-resolution computed
      tomography (HRCT) of the thorax. Progressive lung damage results from a 'vicious
      cycle' of recurrent bacterial infection and a poorly regulated inflammatory
      response. There appear to be two stages to the disease process: the initial
      insult that sets off the disease and then the ongoing, inflammatory process
      encompassing recurrent infection and progressive lung damage. Abnormalities in
      innate and adaptive immunity may predispose to bronchiectasis at both stages.
      Recent immunogenetic evidence suggests that there may be a link between the level
      of natural killer (NK) cell activation and disease susceptibility, implicating a
      predisposing role for innate immune mechanisms. A role for adaptive immune
      mechanisms is suggested by the genetic association of HLA-DR1, DQ5 with increased
      susceptibility to idiopathic bronchiectasis.

PMID- 18608926
TI  - Th17 cells in the setting of Aspergillus infection and pathology.
AB  - Innate and adaptive immune responses act to generate the most effective form of
      immunity for protection against Aspergillus fumigatus. The decision of how to
      respond is still primarily determined by interactions between fungi and cells of
      the innate immune system, but the actions of T cells will feed back into this
      dynamic equilibrium to regulate the balance between pro-inflammatory and anti
      inflammatory signals. The enzyme indoleamine 2,3-dioxygenase, and tryptophan
      metabolites, acting as a bridge between dendritic cells and regulatory T cells,
      pivotally contribute to such a homeostatic condition by taming inflammatory
      responses. IL-23 and the newly described Th17 pathway, by means of negative
      regulation of tryptophan catabolism, play an inflammatory role previously
      attributed to uncontrolled Th1 response. Our data support a model in which IL
      23/IL-17A/Th17-driven inflammation promotes infection and impairs antifungal
      immune resistance. Thus, modulation of the inflammatory response represents a
      potential strategy to stimulate protective immune responses to Aspergillus.

PMID- 18608927
TI  - Multilocus microsatellite typing for Cryptococcus neoformans var. grubii.
AB  - Fifteen randomly selected microsatellites (simple sequence repeats; SSRs), from
      the H99 Cryptococcus neoformans var. grubii (serotype A) genome, were sequenced,
      characterized and applied to sequence 87 clinical and environmental C. neoformans
      var. grubii isolates from 12 different countries based on Multilocus
      Microsatellite Typing (MLMT). Among the 15 SSR loci, three (designated CNG1, CNG2
      and CNG3) were polymorphic, while the remaining 12 SSR loci showed no variations.
      The specific PCR primers of the polymorphic microsatellites, i.e., CNG1, CNG2 and
      CNG3, amplified those loci only from strains of C. neoformans (C. neoformans var.
      grubii, C. neoformans var. neoformans and the AD hybrid) but not from
      Cryptococcus gattii, suggesting a species-specific association. The three
      polymorphic microsatellites are useful markers for strain genotyping, population
      genetic analysis, epidemiological studies, and may be helpful for the diagnosis
      of cryptococcosis due to C. neoformans.

PMID- 18608928
TI  - Characterization and temperature-dependent quantification of heat shock protein
      60 of the immunogenic fungus Alternaria alternata.
AB  - Heat shock proteins or chaperones are found in mitochondrial and cytosolic
      compartments of cells. They are responsible for the correct folding of proteins
      and are up-regulated in reaction to various stressors. In addition, when released
      or presented on the surface of cells, they may play an important role in
      inflammatory and immunomodulating processes. To identify and characterize hsp60
      in the common environmental mold Alternaria alternata, the fungus was cultivated
      and incubated at different temperatures to induce a possible heat shock response.
      Fully automated RNA extraction was followed by quantitative real-time RT-PCR
      targeting A. alternata specific Hsp60 mRNA and subsequent sequencing of the
      amplicon. While Hsp60 mRNA was constitutively expressed in all samples tested, a
      temperature-dependent expression of Hsp60 mRNA was observed. Sequencing revealed
      an identity of more than 85% to other fungal hsp60, indicating the existence of
      this protein in A. alternata.

PMID- 18608929
TI  - Influence of fluoroquinolones on phagocytosis and killing of Candida albicans by
      human polymorphonuclear neutrophils.
AB  - Candida albicans infections often occur during or shortly after antibacterial
      treatment. Phagocytosis by polymorphonuclear neutrophil granulocytes (PMN) is the
      most important primarily defence mechanism against C. albicans. Certain
      antibiotics such as some fluoroquinolones (FQ) are known to influence phagocyte
      functions. Thus, we investigated the influence of older and newer FQ on the
      phagocytosis and killing of C. albicans by human PMN paying special attention to
      CD11b expression of these cells as an indicator of the degree of their
      activation. In order to obtain comprehensive and comparable results we tested 13
      FQ over a wide range of concentrations and in a time dependent manner in a
      standardized approach. When used at therapeutic concentrations, the FQ tested did
      not influence to a clinically significant degree the phagocytosis or the killing
      of C. albicans by human PMN and also not their activation. However, at high
      concentrations those FQ with cyclopropyl-moiety at position N1 showed increase in
      CD11b expression and diminished phagocytosis and oxidative burst.

PMID- 18608931
TI  - Stage-specific innate immune recognition of Aspergillus fumigatus and modulation
      by echinocandin drugs.
AB  - The pulmonary innate immune system clears inhaled Aspergillus fumigatus conidia
      (spores) from terminal airways. Failure to control conidial germination in immune
      compromised hosts can result in hyphal tissue invasion and fatal disease. Insight
      into the molecular recognition of A. fumigatus by host leukocytes indicates that
      the innate immune system exploits obligate changes in fungal cell wall
      composition that occur at the first stage of germination, conidial swelling.
      Germinating spores activate at least two host signal transduction pathways.
      Surface exposure of fungal beta-(1,3) glucan, a polysaccharide constituent of the
      fungal cell wall, triggers dectin-1 signaling by host phagocytes. Spore
      germination leads to the induction of Toll-like receptor (TLR) signaling as well.
      This stage-specific recognition mechanism focuses host antifungal responses on
      cells with the potential for tissue invasion and may serve to limit potentially
      deleterious effects of inflammation in space and time. Fungal beta-(1,3) glucan
      not only activates host innate immune responses but also represents the target of
      echinocandin drugs. The activity of echinocandin drugs has largely been
      understood on the basis of pharmacologic growth inhibition of yeast and moulds,
      resulting in lysis of yeast cells and stunting of dysmorphic hyphae. The
      recognition that fungal beta-1,3 glucan activates dectin-1 signaling suggests
      that echinocandin drugs may exert immune modulatory effects by altering innate
      immune responses to drug-treated fungal cells, a view supported by recent data
      from studies on C. albicans, A. fumigatus, and non-Aspergillus moulds.

PMID- 18608932
TI  - Effective management of pulmonary aspergillosis invading the thoracic spine in a
      child with high risk ALL requiring allogeneic bone marrow transplantation.
AB  - Due to unacceptably high mortality, invasive fungal infections (IFI) have long
      been considered a contraindication against allogeneic stem cell transplantation.
      Despite severe immunosuppression an 11-year-old girl requiring allogeneic bone
      marrow transplant (BMT) for relapsed acute lymphoblastic leukemia was cured of a
      concurrent invasive pulmonary aspergillosis. Treatment comprised combinations of
      liposomal amphotericin B, caspofungin and voriconazole with donor granulocyte
      transfusions. This therapeutic regimen, including the choice of reduced intensity
      conditioning (RIC), allowed the patient to receive an allogeneic BMT. In
      hematological remission the child later developed fatal chronic graft-versus-host
      disease. Combined antifungal treatment and granulocyte support allow for
      effective management of IFI even in allogeneic stem cell transplant recipients.
      However, short-term benefits of RIC may be outweighed by late complications.

PMID- 18608933
TI  - Role of interleukin (IL)-18 in experimental paracoccidioidomycosis.
AB  - Interleukin (IL)-18 has been regarded as a Th1 type cytokine involved in many
      fungal and parasitic infections. Since there have been no studies, as of yet,
      evaluating the role of this cytokine in paracoccidioidomycosis (PCM), we assessed
      the function of IL-18 by using an experimental PCM model. Our results showed that
      IL-18 knockout (IL-18 -/-) BALB/c were more resistant to Paracoccidioides
      brasiliensis than their littermate controls (WT). In fact, mortality rate was
      higher in WT mice and in the first month of infection, the number of colony
      forming units of the etiologic agent recovered from the lungs was greater in WT
      mice. In histopathological analyses, well-formed granulomas were seen in both WT
      and IL-18(-/-) mice. However, substantial differences were observed at the second
      month of infection when epithelioid cells predominated in the lesions of IL-18(-/
      ) mice, which could infer that IL-18 postpones pulmonary healing. The levels of
      IL-10 were significantly higher in IL-18 sufficient mice at early stages of
      infection and therefore account for the delayed fungal clearance observed in WT
      mice. TNF-alpha augmented later in the infection of WT mice, seemingly to
      compensate high levels of IL-10. Our results demonstrated that IL-18 has a
      critical role in protecting BALB/c mice against disseminated PCM.

PMID- 18608934
TI  - A case of Acremonium strictum peritonitis.
AB  - During the past two decades opportunistic fungal infections have emerged as
      important causes of morbidity and mortality in patients with severe underlying
      illnesses. A few cases of Acremonium spp. infections have been described in
      immunocompromised patients, but they have on occasion been reported as the cause
      invasive disease in immunocompetent individuals. Peritonitis is a common clinical
      problem that occurs in patients with end-stage renal disease treated by
      continuous ambulatory peritoneal dialysis (CAPD). Yeasts, or rarely molds, may
      also cause peritonitis in patients on CAPD and we present here a case caused by
      Acremonium strictum.

PMID- 18608935
TI  - A case of endocarditis caused by the yeast Pichia fabianii with biofilm
      production and developed in vitro resistance to azoles in the course of
      antifungal treatment.
AB  - Pichia fabianii, a yeast rarely causing human infections, was isolated from the
      blood of a patient with aortic valve endocarditis. The isolates were initially
      identified biochemically as Candida pelliculosa, but based on direct sequencing
      of the ITS2 region of rRNA, they were subsequently reidentified as P. fabianii.
      Antifungal therapy with fluconazole and later with voriconazole led to the
      development of resistant variants which had high MIC values to both antifungals.
      Strong biofilm formation by this yeast could also have played a role in the
      development of its resistance and allowed for its persistence on the infected
      valve during antifungal therapy. To our knowledge, this is the first published
      case of endocarditis and the fourth human infection caused by this yeast species.

PMID- 18608936
TI  - Invasion process of Candida albicans to tongue surface in early stages of
      experimental murine oral candidiasis.
AB  - We analyzed the morphologic and microbiologic aspects of the process of adhesion
      and invasion in the early stages of Candida albicans oral infection in a murine
      system. ICR mice were anesthetized by intramuscular injection with chlorpromazine
      chloride and then orally inoculated by swabbing with the C. albicans yeast cells.
      Their tongues were resected 1-3h after inoculation, washed sequentially with a
      physiological saline and 0.25% trypsin-solution and then homogenized. The number
      of viable C. albicans cells on the tongue surface was counted and fround to
      increase from 1-3h after inoculation. Most of the Candida cells attached to the
      tongue surface were present in clusters, mainly located in the gaps between
      lingual papillae and were covered with a mucoidal substance. By 3h after
      inoculation, these clusters frequently formed mycelia and could not be easily
      detached from the tongue surface by trypsin treatment. Observation of SEM and
      histological sections stained by Fungiflora Y revealed that the Candida hyphae at
      3h stretched out of the cluster and entered the tongues through the surface.
      These results indicate that Candida hyphae begin to invade the tongue surface
      within 3h after inoculation and suggest that the mucus-like substance covering
      these cells may have an important early role in the interaction between the
      Candida cells and the tongue mucosal epithelium.

PMID- 18608937
TI  - Recognition of laminin by Paracoccidioides brasiliensis conidia: a possible
      mechanism of adherence to human type II alveolar cells.
AB  - This study addresses the recognition of laminin by Paracoccidioides brasiliensis
      conidia, as well as its possible role in the adherence of conidia to A549 cells.
      Adherence of conidia to immobilized laminin was shown to be specific, as anti
      laminin antibodies, soluble laminin or the laminin-derived peptides IKVAV and
      CDPGYIGSR inhibited this interaction. RGD containing peptides and various
      monosaccharides had no effect on adherence, with the exception of N
      acetylneuraminic acid. Pre-treatment of conidia with fibrinogen and fibronectin,
      but not with BSA, also resulted in significant inhibition, suggesting that P.
      brasiliensis conidia might cross-recognize host proteins involved in
      colonization. In assays using transmission electron microscopy, we observed
      internalization of conidia 30 min after exposition to A549 cells. Laminin present
      on the surface of A549 cells shown to serve as mediator of this interaction, with
      a significant decrease in fungal adherence when the epithelial cells were pre
      treated with anti-laminin antibodies or when conidia were pre-incubated with
      either soluble laminin or the laminin-specific peptides. Together these results
      suggest that the recognition of laminin by P. brasiliensis conidia is a key
      process in the interaction with pulmonary epithelial cells, where this
      extracellular matrix protein acts as bridging molecule.

PMID- 18608938
TI  - Yeast diversity in the oral microbiota of subjects with periodontitis: Candida
      albicans and Candida dubliniensis colonize the periodontal pockets.
AB  - The term periodontitis encompasses several polymicrobial infectious diseases, of
      multifactorial etiology, with chronic and aggressive forms. In spite of the
      etiopathogenic differences between these two forms of the disease, few studies
      have analyzed the subgingival colonization by yeast. The objective of this
      investigation was to analyze the composition of the yeast microbiota present in
      the mucosa and subgingival sites of healthy individuals and patients with
      aggressive and chronic periodontitis. For this, samples were recovered from these
      two locations and the yeast recovered identified by phenotypic and genotypic
      methods. Patients with chronic periodontitis showed significant differences in
      relation to the other groups with respect to carrier status (69.2% versus 35.7%
      of healthy individuals; [chi(i)(2) test; p=0.014]), the total number of isolated
      colony forming units or CFU (mean and ranges 281.6 (0-6048) [K-W(2)=6.998;
      p=0.03]), the Simpson diversity index (I) in site b (I(b)=0.344 versus healthy
      subjet and aggresive periodontitis where I=0 [multiple t-test comparisons with
      the Bonferronni correction, p<0.05]), and the species profile. Interestingly, in
      spite of the varied profiles of the species present in the mucosa of the three
      groups analyzed we noted that only C. albicans and C. dubliniensis were capable
      of colonizing the periodontal pockets in patients with chronic periodontitis,
      while only C. albicans was identified in the subgingiva of healthy individuals
      and patients with aggressive periodontitis.

PMID- 18608939
TI  - An intrafamilial transmission of Arthroderma benhamiae in Canadian porcupines
      (Erethizon dorsatum) in a Japanese zoo.
AB  - An intra-familial transmission of Arthroderma benhamiae in Canadian porcupines
      (Erethizon dorsatum) housed in a Japanese zoo was studied. The family consisted
      of an adult couple and two offspring (a male and a female). The porcupettes, born
      in Japan, showed severe hair loss while the parent animals, imported from the
      USA. (male) and Canada (female), showed mild symptoms or were asymptomatic.
      Morphologically identical Tricophyton spp. isolates were recovered within seven
      days from quills of all animals on chloramphenicol-supplemented potato dextrose
      agar plates incubated at 37 degrees C. Two representative colonies from each
      animal were identified as Arthroderma benhamiae Americano-European race based on
      mating type (+) and the internal transcribed spacer (ITS) 1-5.5S-ITS 2 region of
      the rRNA gene sequences (AB236404-AB236408). The present cases constituted the
      second isolation of dermatophytes from porcupines. There were two different ITS
      types, i.e., the predominant one isolated from all animals and a secondary one
      recovered from only the mother porcupine. The sequences have never been recorded
      in Japan or in the GenBank database to the best of our knowledge. In addition,
      they were located at a cluster involving the type strain and mating strains of A.
      benhamiae Americano-European race and its F1 progeny. In contrast, 28 rodents
      (eight species) and three insectivora (1 species) exhibited in the petting zoo
      were negative for any dermatophytes as determined by culture.

PMID- 18608940
TI  - Phospholipase activity of yeasts from wild birds and possible implications for
      human disease.
AB  - Over the last decades, reports on yeast infections in humans have increased
      especially with respect to immunocompromised individuals. Phospholipases are
      enzymes which may be associated with pathogenic processes caused by opportunistic
      yeasts. Phospholipase activity (ph.a.) was investigated in 163 isolates of 13
      species of yeasts. A total of 133 isolates were obtained through the screening of
      a total of 768 cloacae of wild birds (Group I: 182 birds of prey; Group II: 165
      passeriformes and Group III: 421 other wild migratory birds), while 30 isolates
      were recovered from the droppings of birds housed in 32 distinct aviaries (Group
      IV). Phospholipase production was evaluated and quantified at 2 and 5 day pre
      incubation (Pr.t) and incubation times (I.t). Isolates from cloacae (48.1%) and
      excreta (73.3%) produced ph.a. with the highest values registered after 5 days of
      I.t. Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae, C. pelliculosa,
      Cryptococcus albidus, C. laurentii, Trichosporon beigelii, and Saccharomyces
      cerevisiae displayed the highest ph.a. after 2 days of Pr.t while Candida famata,
      C. guilliermondii and Cryptococcus neoformans after 5 days of Pr.t. Ph.a. was
      never found in Rhodotorula rubra isolates recovered from the cloacae of wild
      birds. Isolates (73.3%) from bird droppings showed a higher ph.a. than those from
      cloacae thus indicating that wild birds not only act as carriers but may also
      spread phospholipase-producing yeasts in the environment.

PMID- 18608941
TI  - Systemic and mucosal immunization with Candida albicans hsp90 elicits hsp90
      specific humoral response in vaginal mucosa which is further enhanced during
      experimental vaginal candidiasis.
AB  - The Candida albicans heat shock protein 90 kDa (hsp90-CA) is an important target
      for protective antibodies in disseminated candidiasis of experimental mice and
      humans. Hsp90-CA is present in the cell wall of Candida pseudohyphae or hyphae-
      typical pathogenic morphotypes in both mucosal and systemic Candida infections.
      However, the potential protective effects of hsp90-CA-specific antibodies in
      vaginal candidiasis has not yet been reported. In the present study we used
      various vaccine formulations (recombinant hsp90-CA protein and hsp90-CA-encoding
      DNA vaccine) and routes of administration (intradermal, intranasal, and
      intravenous) to induce both hsp90-CA-specific systemic and vaginal mucosa immune
      responses in experimental BALB/c mice. The results showed that intradermal
      recombinant hsp90-CA protein priming, followed by intranasal or intradermal
      recombinant hsp90-CA protein boosting induced significant increases in both serum
      and vaginal hsp90-CA-specific IgG and IgA antibodies compared to the control
      group, as well as enhanced hsp90-CA-specific splenocyte responses in vitro. In
      the intradermally boosted group, subsequent experimental vaginal Candida
      infection induced additional increases in the hsp90-CA specific IgG isotype,
      suggesting that Candida has the ability to induce a local hsp90-specific antibody
      (IgG) response during vulvovaginal candidiasis. Further work is required to
      elucidate the importance of immunity to highly conserved antigens during
      infection of the human female reproductive tract where a balance between immunity
      to and tolerance for commonly antigens such as hsp90 is necessary for the
      maintenance of fertility.

PMID- 18608942
TI  - Models of medical education in Australia, Europe and North America.
AB  - BACKGROUND: The universal goal of medical education is to train excellent
      physicians, able to maintain the health of individuals and communities. The route
      to achieving this goal has shifted over time. This paper describes the absolutes
      and ambiguities of philosophical vision, responsiveness to stakeholders,
      curriculum content and delivery, and assessment of trainees and training programs
      across much of the developed world. DESCRIPTION: Traditional medical education is
      content focused and organized by organ systems. Newer curricula, informed by
      current learning theories, emphasize a competencies based approach, with clinical
      scenarios at the centre of teaching and assessment of students. Associated with
      this is a shift from the in-depth knowledge of the specialist to a 'what must a
      generalist know' approach. These models are explored as are options for
      curriculum delivery, input from governments, students, the public and faculty,
      and methods and importance of accreditation. CONCLUSION: The goals and the
      process of training physicians to achieve these exhibit numerous commonalities
      across time and place throughout the developed world while still allowing for
      cultural or national adaptations. All models and content aim for minimum basic
      knowledge, while emphasizing communication skills, cultural awareness and
      professionalism amongst future physicians.

PMID- 18608944
TI  - Teaching medical students about medically unexplained illnesses: a preliminary
      study.
AB  - BACKGROUND: This study examined how an interactive seminar focusing on two
      medically unexplained illnesses, chronic fatigue syndrome (CFS) and fibromyalgia,
      influenced medical student attitudes toward CFS, a more strongly stigmatized
      illness. METHODS: Forty-five fourth year medical students attended a 90 minute
      interactive seminar on the management of medically unexplained illnesses that was
      exemplified with CFS and fibromyalgia. A modified version of the CFS attitudes
      test was administered immediately before and after the seminar. RESULTS: Pre
      seminar assessment revealed neutral to slightly favorable toward CFS. At the end
      of the seminar, significantly more favorable attitudes were found toward CFS in
      general (t (42) = 2.77; P < 0.01) and for specific items that focused on (1)
      supporting more CFS research funding (t (42) = 4.32; P < 0.001; (2) employers
      providing flexible hours for people with CFS (t (42) = 3.52, P < 0.01); and (3)
      viewing CFS as not primarily a psychological disorder (t (42) = 2.87, P < 0.01).
      Thus, a relatively brief exposure to factual information on specific medically
      unexplained illnesses was associated with more favorable attitudes toward CFS in
      fourth year medical students. CONCLUSION: This type of instruction may lead to
      potentially more receptive professional attitudes toward providing care to these
      underserved patients.

PMID- 18608945
TI  - Medical student views on teaching about sexual dysfunction.

PMID- 18608946
TI  - Turning words into numbers: establishing an empirical cut score for a letter 
      graded examination.
AB  - BACKGROUND: High stakes postgraduate specialist certification examinations have
      considerable implications for candidates' future careers. The cut score i.e.
      pass/fail mark of such examinations needs to be determined in a defensible and
      credible manner. A number of methods, suitable for use with numeric scoring
      methods, have been described. Determining the cut score of letter-graded
      examinations is, however, not described in the literature. AIM: The aim of this
      study was to determine a defensible and credible method for deriving the cut
      score of a letter-graded examination. METHOD: The cut score of the Fellowship
      examination of the College of Physicians of South Africa was estimated using a
      novel method. This method was validated by comparing the results obtained to
      those obtained using the contrasting groups method. RESULTS: By using the
      examiners' decision as the 'gold standard' we found that a cut score of 50% best
      approximated the cutpoint of this letter-graded examination, achieving a
      sensitivity and specificity of 83.7% and 82.8% respectively. CONCLUSION: This
      paper describes a useful strategy for estimating the cut score of letter-graded
      examinations.

PMID- 18608947
TI  - Twelve tips on rural medical placements:  what has worked to make them
      successful.
AB  - Providing undergraduate and post-graduate rural training opportunities aids rural
      medical recruitment. Medical schools that provide rural educational placements,
      and the communities that host those placements, must give serious consideration
      to the structure and supports required to ensure both quality and enjoyment of
      rural placements. This paper presents tips for success gleaned from the results
      of experience in providing rural placement opportunities to medical students
      throughout their medical school experience.

PMID- 18608948
TI  - Learner-centred feedback using remote  assessment of clinical procedures.
AB  - This paper describes the Imperial College Feedback and Assessment System (ICFAS)
      and explores its feasibility in supporting the learning of practical clinical
      procedures. ICFAS is an innovative combination of existing technologies which
      brings together video recording, networked mobile computers (laptop and handheld)
      and content management software. The aim is to observe, record, assess and
      provide feedback on multiple simulated encounters. We have developed ICFAS within
      the framework of our Integrated Procedural Performance Instrument (IPPI)
      (Kneebone et al. 2006a,b), providing a technology-based 'feedback space' for
      maximizing educational value.

PMID- 18608949
TI  - Do pediatric fellows recognize the importance and contribution of training to
      mastery of the general competencies?
AB  - BACKGROUND: Six general competencies form the framework for accreditation of
      postgraduate fellowship programs and maintenance of certification for physician
      specialists. Fellows' perceptions of these competencies, however, remain
      unexplored. AIMS: To examine fellows' perceptions of the importance of the
      competencies to medical education and the contribution of fellowship training to
      mastery of the competencies, and to explore the alignment of the competencies
      with critical learning experiences. METHODS: Semi-structured interviews were
      conducted with 20 pediatric fellows in five divisions at one institution. Fellows
      recounted critical learning experiences, rated each competency for importance and
      contribution of training, and explained their ratings. Interviews were analyzed
      using standard qualitative methods. RESULTS: Fellows assigned high ratings to
      medical knowledge and patient care for importance and contribution of training to
      mastery, referring to these competencies as 'staples of training'. They rated
      interpersonal and communication skills and professionalism higher for importance
      than contribution of training, viewing them as inherent traits or learned before
      fellowship. Fellows were unfamiliar with practice-based learning and improvement
      and systems-based practice and typically perceived them as secondary to training.
      Descriptions of critical learning experiences substantiated competency ratings
      for medical knowledge and patient care, but not practice-based learning and
      improvement. CONCLUSIONS: Fellows perceive traditional knowledge and skills of
      medical practice as fundamental to postgraduate training, but other competencies
      as less central.

PMID- 18608950
TI  - Web 2.0 and social software: the medical student way of e-learning.
AB  - BACKGROUND: A wide range of social software has become readily available to young
      people. There is increasing interest in the exciting possibilities of using
      social software for undergraduate medical education. AIMS: To identify the nature
      and extent of the use of social software by first year medical students. METHOD:
      A structured self-administered questionnaire survey of 212 students. RESULTS:
      Over 90 percent used instant messaging and social networking sites were highly
      used (70 percent). There was no significant difference between males and females.
      Blogs were read by about a fifth of students and a small number (8%) wrote their
      own blogs. A fifth of males stated that they were users of media sharing and
      contributed to wikis. Social bookmarking was rarely used by either sex.
      CONCLUSION: Medical educators need to recognise the potential of social software
      in undergraduate medical education but it is essential that students maintain the
      informality and privacy of these sites. The challenge for all medical educators
      is how to integrate social software into current curricula and institutional
      Virtual Learning Environments (VLEs).

PMID- 18608951
TI  - How to improve the medical students' communication skills.

PMID- 18608952
TI  - Acquisition of learning outcomes by students from the Medical School of the
      University of Barcelona (Catalonia, Spain): a student survey.
AB  - BACKGROUND: In 2001, in order to improve the curriculum, the medical school of
      the University of Barcelona began discussions aimed at defining specific learning
      outcomes for its medical graduates and, subsequently, evaluating the acquisition
      of these competencies. AIM: To report the views of our medical students regarding
      the extent to which they have acquired the learning outcomes previously defined
      by the faculty. METHOD: A questionnaire was administered to seventy final year
      students, who had finished all the course clerkships and they were asked to
      indicate on a Likert scale their perceived level of acquisition of each learning
      outcome. RESULTS: Overall, the students report an adequate level of competency
      and consider themselves able to meet skills targets under supervision in eight of
      the eleven domains investigated. In three of the domains (patient management,
      medical information search skills, and decision-making skills and clinical
      reasoning and judgment) students regarded themselves as only partially competent.
      These results agree with the global course score of the students, according to
      the medical school assessment system. CONCLUSIONS: The results will allow us to
      make curricular and methodological changes in order to implement a new outcome
      based curriculum.

PMID- 18608954
TI  - Medical education in first aid  and basic life support in the  Netherlands.

PMID- 18608955
TI  - The shadowing period - "Could do better"

PMID- 18608956
TI  - Early student-patient contacts in general practice: an approach based on
      educational principles.
AB  - BACKGROUND: Clinical teaching and learning is generally seen as an educationally
      sound approach, but the clinical environment does not always offer optimal
      conditions to facilitate students' learning processes. AIMS: To show how insights
      on constructing a good learning environment for student-patient contacts in real
      practice can be translated into an undergraduate clinical general practice
      programme in Year 3 and to study its feasibility. METHOD: Literature search,
      yielding starting points for the development of the new programme and
      questionnaire evaluation of the programme. RESULTS: Six starting points for a
      good learning environment for early student-patient contacts: continuing exposure
      to patients,transformation of experience into knowledge, active role of students,
      supervision and feedback, time and space for teaching and teacher training were
      translated into a the new programme. The evaluation showed that the programme was
      feasible and well received by students and GPs, although some improvements are
      possible. CONCLUSION: In a curriculum with clear goals for early student-patient
      contacts, it is feasible to implement an early clinical programme in general
      practice based on educational principles.

PMID- 18608958
TI  - Service user perspectives about their roles in undergraduate medical training
      about mental health.
AB  - BACKGROUND: Current policy states that 'service users and carers should be
      involved in planning, providing and evaluating training for all health care
      professionals. We wished to explore service users' views regarding undergraduate
      psychiatry. AIMS: We aimed to explore user perspectives on the specific role of
      service users in the delivery of teaching psychiatry. METHOD: The study design
      was qualitative and used focus groups. The study took place in a community
      context with one focus group in Leeds, Leicester, Lincoln and Nottingham. Four
      focus groups were run with a total of 28 participants (16 women and 12 men, all
      white). No exclusion criteria were applied. The lead of each group were contacted
      and they then recruited volunteers from their membership. RESULTS: The key
      findings were that participants felt that service users could play important
      roles in contextualising the part mental health plays in people's lives; dispel
      myths and fantasies about mental health; offer positive aspects of mental health
      to counterbalance the media; illustrate diversity within mental health and hope
      and recovery. Participants also identified the potential challenges to their
      participation including vulnerabilities especially at critical points in people's
      illnesses; perceived credibility - lack of support from some involved in academic
      roles; lack of appropriate training and support and issues of power and lack of
      genuine partnership in the planning and delivery of teaching. They were
      favourable about the development of guidelines as long as they involved a range
      of perspectives. CONCLUSIONS: Service users present a range of ways in which they
      could be involved to enhance the educational experience of medical students in
      psychiatry.

PMID- 18608959
TI  - Improvement of residents' clinical competency after the introduction of new
      postgraduate medical education program in Japan.
AB  - BACKGROUND: In 2004, the Japanese government reformed the monospecialty-oriented
      postgraduate medical education (PGME) program and introduced a new PGME program
      to develop the primary care skills of physicians by mandatory rotation through
      different clinical departments. AIMS: (1) to evaluate whether residents' clinical
      competency improved after the introduction of the new PGME program and (2) to
      compare the change in competency between university and non-university residents.
      METHOD: Surveys were conducted before and after the introduction of the new PGME,
      i.e. in 2004 (response rate 88%) and 2006 (88%). One in every five residents was
      sampled, and the study subjects were 2474 second-year residents (1762 university
      residents and 712 non-university residents) in 2004 who were about to complete
      the previous PGME program and 1166 second-year residents (487 and 679) in 2006
      who were the first generation to complete the new PGME program. The clinical
      competency ratings were measured by the proportion of respondents reporting
      'experience' in 24 clinical specialties and three items regarding the use of
      medical records and 'confidence' in 35 clinical skills and knowledge items in
      four areas (i.e basic medicine, allied areas, behavioural science and social
      medicine, and clinical research). RESULTS: Compared to the residents in 2004, the
      clinical experience and confidence level of the residents increased dramatically
      for almost all of the surveyed items in 2006, regardless of the type of teaching
      hospital (chi-square or Fisher's exact tests, P < 0.0001). The marked improvement
      in the clinical competency of university residents was noticeable, resulting in
      the disappearance of the historical trend for non-university residents to obtain
      significantly more clinical experience than university residents. CONCLUSIONS:
      The new PGME program appears to have been successful at improving both the
      clinical experience and confidence levels of medical residents, especially at
      university hospitals.

PMID- 18608960
TI  - Planning and implementing a collaborative clinical placement for medical, nursing
      and allied health students: a qualitative study.
AB  - BACKGROUND: Clinical placements have been traditionally offered on a profession
      specific basis, and as a result, we have a good understanding of salient issues
      related to their development and delivery. We know less about the planning and
      implementation of collaborative clinical placements. AIMS: This paper presents
      key findings from a qualitative study that explored the collaborative processes
      connected to an interprofessional planning group who created and implemented a
      clinical placement for medical, nursing and allied health students. METHODS: An
      ethnographic approach was employed to explore the successes and challenges
      connected with the planning group's interprofessional work. Interviews,
      observations and documents were gathered over two years to obtain a comprehensive
      understanding of this placement. RESULTS: The study found that while the planning
      group achieved a number of successes in their work including the implementation
      of a well-received pilot placement, their enthusiasm for the placement created a
      number of challenges. In particular, it resulted in them neglecting their roles,
      responsibilities and collaborative group processes, which created difficulties in
      their ability to work together. In addition, a turnover of members, changes in
      management and a hospital reorganization inhibited the group's collaborative
      work. CONCLUSIONS: Collaboration around the planning and implementation of
      interprofessional placements is a complex venture. In striving for success in
      this work, planning groups need to focus their attention on both internal group
      based factors as well external organizational factors.

PMID- 18608961
TI  - From theory to practice in learning about healthcare associated infections:
      reliable assessment of final year medical students' ability to reflect.
AB  - BACKGROUND: Healthcare associated infection affects 9% of patients admitted to
      hospital. One of the greatest challenges in addressing this problem is
      transferring theory to practice in relation to hand hygiene. Developing the
      ability to reflect can promote this transfer. This study illustrates how an
      instrument to assess the reflective ability of final year medical students was
      applied to the context of hand hygiene within the infection control cleanliness
      champion programme (CCP) and demonstrated inter-rater reliability at all three
      levels of reflection. The results suggest behaviour change in relation to
      practice. METHODS: One hundred and thirty two reflective accounts were used for
      this study, provided by 44 5th year medical students. Each student had written
      three reflective accounts for each part of the hand hygiene unit. Results show
      that the inter-rater agreement was consistently high for all three levels of
      reflection. However, the least consistent was at reflective level three.
      CONCLUSIONS: These results suggest that the students were able to link theory to
      practice following the completion of the CCP. It could also indicate that
      assessors might require more skills and knowledge to enable effective and
      consistent examination of all areas of reflection.

PMID- 18608963
TI  - Working effectively with interpreters: a model curriculum for physician assistant
      students.
AB  - BACKGROUND: Effective patient-provider communication is crucial to achieving good
      health care outcomes. To accomplish this with patients of limited English
      proficiency, learning to work effectively with interpreters is essential. AIMS:
      The primary goal of this study was to determine if physician assistant students
      could effectively use interpreters to communicate with Spanish speaking patients
      after implementation of a cultural competency and Medical Spanish curriculum.
      METHOD: In year one of a three year implementation process, a module for teaching
      students to work effectively with interpreters was developed and implemented in
      the Wake Forest University School of Medicine Department of Physician Assistant
      Studies. After four hours of orientation, practice and role play, students were
      observed and recorded during a standardized patient assessment and evaluated by
      clinicians as well as by trained, bi-lingual evaluators. RESULTS: In the Class of
      2007, 94% (43 students) and in the Class of 2008, 96% (47 students) demonstrated
      competence. CONCLUSIONS: Our findings highlight the feasibility and usefulness of
      training students to work effectively with interpreters. Evaluation and feedback
      from students and faculty have been positive. Cost for this curriculum
      enhancement was reasonable, making it feasible to introduce the training into a
      wide variety of medical and allied health programs.

PMID- 18608964
TI  - A simulation-based biodefense and disaster  preparedness curriculum for internal 
      medicine residents.
AB  - AIMS: Disaster and bioterrorism preparedness is poorly integrated into the
      curricula of internal medicine residency programs. Given that victims may present
      to a variety of healthcare venues, including primary care practices, inpatient
      hospital wards, and intensive care units, we developed a curriculum to address
      this need. METHODS: The curriculum consisted of four didactic sessions with
      supplemental readings covering biologic, chemical, and radiologic agents, as well
      as public health infrastructure. All 30 internal medicine resident participants
      also underwent a four hour training seminar at a high fidelity human simulation
      center. Instruction included the use of personal protective equipment (PPE)and
      participation in simulated scenarios utilizing technologically sophisticated
      mannequins with monitoring and interactive capability. Sessions were videotaped,
      reviewed with participants, and followed by self-evaluation and constructive
      feedback. RESULTS: Compared to a control group of residents who did not undergo
      training, the participants' level of knowledge was significantly better, with
      mean objective test scores of 66.8%+/-11.8% SD vs. 50%+/-13.1% SD, p < 0.0001.
      Although there was a trend toward increasing knowledge with increasing level of
      training in the control group, this difference was not significant. Subjective
      preparedness was also significantly better in the intervention group (p <
      0.0001). Objective improvements were not maintained after one year. CONCLUSIONS:
      In this pilot study, a disaster-preparedness curriculum including simulation
      based training had a positive effect on residents' knowledge base and ability to
      respond to disaster. However, this effect had diminished after one year,
      indicating the need for reinforcement at regular intervals.

PMID- 18608965
TI  - Patients consulting with students in general practice: survey of patients'
      satisfaction and their role in teaching.
AB  - BACKGROUND: General practice is a common setting for medical students' clinical
      training. However, little is known about patients' views on consulting with
      senior students. AIMS: To investigate patients' attitudes to consultations
      conducted by senior students alone, before patients saw their GP; and to enquire
      into patients' perception of their teaching role. METHOD: Adult patients
      attending 50 health centres in Sweden completed a questionnaire directly after
      their consultation with a fifth-year medical student and their GP. Results were
      analysed quantitatively and qualitatively. RESULTS: The questionnaire was
      completed by 495 patients, and 92% were satisfied with their consultation.
      Reasons were personal gain as well as altruism. Almost all patients were prepared
      to consult with a student again, however in a third of cases conditional on the
      nature of their presenting complaints. Emotional problems and intimate
      examinations could cause reluctance. Patients' conception of their teaching role
      supported previous research: patients as "facilitators of students" development
      of professional skills and as "experts" or "exemplars" of their condition. An
      additional theme, patients as "part of a real context", emerged. CONCLUSIONS:
      Patients in general practice have a positive view towards consulting with senior
      students. Even unprepared patients see themselves as contributors to teaching,
      and their capacity in this respect is probably under-utilized.

PMID- 18608966
TI  - The assessment of student reasoning in the  context of a clinically oriented PBL
      program.
AB  - BACKGROUND: Doctors' clinical reasoning ability significantly impacts upon their
      level of clinical competence. Throughout medical training students are given the
      opportunity to develop their reasoning ability in order to become appropriately
      clinically competent by graduation. AIM: To develop an instrument to assess
      students' reasoning ability on a written case-based question which was aligned to
      their learning in a PBL program. METHOD: An instrument with 10 criteria centred
      upon hypothesis generation, learning issues and mechanistic explanations was
      developed. Experienced clinical and medical educators validated the instrument,
      prior to its use with 145 undergraduate first-year medical students. RESULTS: The
      results enabled the establishment of the strengths and weaknesses in the
      reasoning performances of individuals, as well as the overall cohort. The
      instrument's Cronbach alpha coefficient was 0.94, and it had high inter-rater and
      intra-rater reliability. Further validation of the instrument's performance was
      established through qualitative evidence derived from student interviews and
      tutor reports for this cohort. CONCLUSIONS: Aligning written assessment to the
      PBL process enables students and teachers to better understand how the reasoning
      process is developing for individuals and a cohort, and provides a basis for
      further investigation into the development of student clinical reasoning.

PMID- 18608968
TI  - The student voice: recognising the hidden and informal curriculum in medicine.
AB  - BACKGROUND: While there has been broad-based recognition of the concepts of both
      the informal and the hidden curriculum, these elements have been poorly described
      in the medical education literature from the student perspective. METHODS: The
      Student Voice study used focus groups to explore student views of the informal
      and hidden curriculum, to establish the importance of this curriculum for the
      students, and to identify how students perceive the role of this curriculum in
      aiding their learning in medical school. RESULTS: Students recognised that the
      informal curriculum existed to a greater degree in Medicine than in other degree
      programs, and that it revolved around the processes of 'being' a doctor.
      CONCLUSION: The students' concepts of the informal curriculum highlighted a
      tension between the importance of the informal curriculum in focusing their
      learning on what was important to know for assessment, and the extremely valuable
      components of the informal curriculum that remained predominantly unassessed.

PMID- 18608969
TI  - Online collaborative learning: quantifying how people learn together online.
AB  - BACKGROUND: Curtis and Lawson described a simple but useful method to quantify
      the interactions of students collaboratively learning online using content
      analysis to categorise behaviour. We extended Curtis and Lawson's method by
      allowing responses to interactions to be recorded and analysed. Populations can
      be partitioned into groups of arbitrary size to address a variety of research
      questions. AIMS: This paper describes an attempt to explore the utility of this
      extended method when applied to real online collaborative learning. METHOD: Using
      an illustrative example from a postgraduate online medical course for general
      practitioners, we show how rich the dynamics of online interaction can be and how
      courses can be analysed to suggest improvements. RESULTS: We found that tutors
      and students differ in how they behave when learning online and according to task
      type. CONCLUSIONS: We propose that our method could be useful to measure the
      effectiveness of collaborative exercises and can be applied wherever research is
      committed into online group behaviour.

PMID- 18608972
TI  - How emotion affects older adults' memories for event details.
AB  - As adults age, they tend to have problems remembering the details of events and
      the contexts in which events occurred. This review presents evidence that emotion
      can enhance older adults' abilities to remember episodic detail. Older adults are
      more likely to remember affective details of an event (e.g., whether something
      was good or bad, or how an event made them feel) than they are to remember non
      affective details, and they remember more details of emotional events than of non
      emotional ones. Moreover, in some instances, emotion appears to narrow the age
      gap in memory performance. It may be that memory for affective context, or for
      emotional events, relies on cognitive and neural processes that are relatively
      preserved in older adults.

PMID- 18608974
TI  - Why recall our highs and lows: relations between memory functions, age, and well
      being.
AB  - This study examined whether positive and negative memories (life story high and
      low points) were differentially used for reminiscence functions concerning self
      and social aspects of reminiscing, and relations between function use and well
      being in two age groups. Life story high and low points were collected from a
      sample of emerging (n =56) and older (n =55) adults, as well as a measure of the
      use of these memories for the self-functions of death preparation, identity, and
      problem solving, and the social functions of conversation and teach/inform, and a
      measure of psychological well-being. Memories were also coded for whether or not
      they contained a redemptive narrative structure (from emotionally negative to
      emotionally positive). Results showed that the endorsement of reminiscence
      functions did differ by memory type, with high points more often endorsed for the
      functions of identity, teach/inform, and conversation than low points. These main
      effects were qualified by memory type x age interactions. The use of these
      functions for each kind of memory was also related to well-being, but
      differentially for older and younger people, and redemptive sequencing was
      especially important to the well-being of the younger group. Findings are
      discussed in terms of the importance of different emotional memories for self and
      well-being at different points in the lifespan.

PMID- 18608973
TI  - Semantic and self-referential processing of positive and negative trait
      adjectives in older adults.
AB  - The beneficial effects of self-referential processing on memory have been
      demonstrated in numerous experiments with younger adults but have rarely been
      studied in older individuals. In the present study we tested young people,
      younger-older adults, and older-older adults in a self-reference paradigm, and
      compared self-referential processing to general semantic processing. Findings
      indicated that older adults over the age of 75 and those with below average
      episodic memory function showed a decreased benefit from both semantic and self
      referential processing relative to a structural baseline condition. However,
      these effects appeared to be confined to the shared semantic processes for the
      two conditions, leaving the added advantage for self-referential processing
      unaffected These results suggest that reference to the self engages qualitatively
      different processes compared to general semantic processing. These processes seem
      relatively impervious to age and to declining memory and executive function,
      suggesting that they might provide a particularly useful way for older adults to
      improve their memories.

PMID- 18608975
TI  - Committing memory errors with high confidence: older adults do but children
      don't.
AB  - We investigated lifespan differences of confidence calibration in episodic
      memory, particularly the susceptibility to high-confidence errors within samples
      of children, teenagers, younger adults, and older adults. Using an associative
      recognition memory paradigm, we drew a direct link between older adults'
      associative deficit and high-confidence errors. We predicted that only older
      adults would show high-confidence error even though their memory performance was
      at a similar level to that of children. Participants of all ages showed higher
      confidence following correct responses compared to incorrect responses,
      demonstrating the ability to calibrate subjective confidence in relation to
      memory accuracy. However, older adults were disproportionately more likely to
      indicate high confidence following erroneously remembered word pairs than
      participants of the other three age groups. Results are discussed in relation to
      the misrecollection account of high-confidence errors and ageing-related decline
      in hippocampus-dependent episodic memory functions.

PMID- 18608976
TI  - Differential effects of age on prospective and retrospective memory tasks in
      young, young-old, and old-old adults.
AB  - Remembering to do something in the future (termed prospective memory) is
      distinguished from remembering information from the past (retrospective memory).
      Because prospective memory requires strong self-initiation, Craik (1986)
      predicted that age decrements should be larger in prospective than retrospective
      memory tasks. The aim of the present study was to assess Craik's prediction by
      examining the onset of age decline in two retrospective and three prospective
      memory tasks in the samples of young (18-30 years), young-old (61-70 years), and
      old-old (71-80 years) participants recruited from the local community. Results
      showed that although the magnitude of age effects varied across the laboratory
      prospective memory tasks, they were smaller than age effects in a simple three
      item free recall task. Moreover, while reliable age decrements in both
      retrospective memory tasks of recognition and free recall were already present in
      the young-old group, in laboratory tasks of prospective memory they were mostly
      present in the old-old group only. In addition, older participants were more
      likely to report a retrospective than prospective memory failure as their most
      recent memory lapse, while the opposite pattern was present in young
      participants. Taken together, these findings highlight the theoretical importance
      of distinguishing effects of ageing on prospective and retrospective memory, and
      support and extend the results of a recent meta-analysis by Henry, MacLeod,
      Phillips, and Crawford (2004).

PMID- 18608977
TI  - Directed forgetting of complex pictures in an item method paradigm.
AB  - An item-cued directed forgetting paradigm was used to investigate the ability to
      control episodic memory and selectively encode complex coloured pictures. A
      series of photographs was presented to 21 participants who were instructed to
      either remember or forget each picture after it was presented. Memory performance
      was later tested with a recognition task where all presented items had to be
      retrieved, regardless of the initial instructions. A directed forgetting effect-
      that is, better recognition of "to-be-remembered" than of "to-be-forgotten"
      pictures--was observed, although its size was smaller than previously reported
      for words or line drawings. The magnitude of the directed forgetting effect
      correlated negatively with participants' depression and dissociation scores. The
      results indicate that, at least in an item method, directed forgetting occurs for
      complex pictures as well as words and simple line drawings. Furthermore, people
      with higher levels of dissociative or depressive symptoms exhibit altered memory
      encoding patterns.

PMID- 18608978
TI  - Does overgeneral autobiographical memory result from poor memory for task
      instructions?
AB  - Considerable previous research has shown that retrieval of overgeneral
      autobiographical memories (OGM) is elevated among individuals suffering from
      various emotional disorders and those with a history of trauma. Although previous
      theories suggest that OGM serves the function of regulating acute negative
      affect, it is also possible that OGM results from difficulties in keeping the
      instruction set for the Autobiographical Memory Test (AMT) in working memory, or
      what has been coined "secondary goal neglect" (Dalgleish, 2004). The present
      study tested whether OGM is associated with poor memory for the task's
      instruction set, and whether an instruction set reminder would improve memory
      specificity over repeated trials. Multilevel modelling data-analytic techniques
      demonstrated a significant relationship between poor recall of instruction set
      and probability of retrieving OGMs. Providing an instruction set reminder for the
      AMT relative to a control task's instruction set improved memory specificity
      immediately afterward.

PMID- 18608979
TI  - Recognition hypermnesia: how to get it.
AB  - Although recall hypermnesia (enhanced recall) over time with repeated testing has
      by now become an established empirical fact, its recognition counterpart,
      recognition hypermnesia, has defied clear-cut laboratory confirmation. In four
      studies, which relied on the retrieval component of recognition memory, it was
      shown that recognition memory, indexed by d', reliably improved over three
      successive recognition tests. The stimuli consisted of 140 cartoons, each
      comprising a picture and a verbal caption. Recognition memory was tested on
      transforms or part-forms (parts) of the original stimulus material (pictures
      only, verbal paraphrases of the pictures, the latent content of the cartoons, or
      the combination of paraphrases and latent contents). The strongest effects were
      obtained when the originally presented cartoons were tested on their latent (deep
      semantic) contents. Recognition hypermnesia for part-forms or transforms of
      earlier presented stimuli has potentially wide-ranging implications since real
      world recognition--of faces, texts, visual scenes--usually involves recognising
      stimuli that are variants, not exact copies, of the originally encountered
      materials.

PMID- 18608980
TI  - Age-related neural activity during allocentric spatial memory.
AB  - Age-related decline in allocentric (viewer-independent) spatial memory is seen
      across species. We employed a virtual reality analogue of the Morris Water Maze
      to study the effect of healthy ageing on neural activity during allocentric
      spatial memory using functional magnetic resonance imaging. Voxel-based
      morphometry was used to ascertain hippocampal volumetric integrity. A widespread
      neural network comprising frontal, parietal, occipital, thalamic, and cerebellar
      regions was activated in young and older adults, but only young adults
      significantly activated bilateral hippocampus and left parahippocampus, as well
      as right frontal pole and dorso-lateral prefrontal cortex (DLPFC) during encoding
      and right DLPC during retrieval. Hippocampal grey matter volume was unchanged in
      older adults; however, prefrontal and parahippocampal functional attenuation was
      accompanied by volumetric reduction. We conclude that the decline in allocentric
      spatial memory with age is associated with attenuated hippocampal function, as
      well as compromised function and structure of prefrontal and parahippocampal
      regions.

PMID- 18608987
TI  - Modeling of cellular metabolism and microcirculatory transport.
AB  - Oxygen and other substrates, waste products, hormone messengers, and cells and
      other particles of the immune system are all transported in a closed-loop
      circulatory system in vertebrates, within which pumped blood travels to within
      diffusion distances of practically every cell in the body. Exchange of oxygen and
      carbon dioxide in the pulmonary capillaries and absorption of nutrients in the
      gut provide the circulating blood with biochemical reactants to sustain
      bioenergetic processes throughout the body. Inputs and outputs transported by the
      microcirculation are necessary to drive the open-system nonequilibrium chemical
      reactions of metabolism that are essential for cellular function. In turn,
      metabolically derived signals influence microcirculatory dynamics. Indeed, the
      microcirculation is the key system that ties processes at the whole-body level of
      the cardiovascular system to subcellular phenomena. This tight integration
      between cellular metabolism and microcirculatory transport begs for integrative
      simulations that span the cell, tissue, and organ scales.

PMID- 18608981
TI  - Theoretical models of microvascular oxygen transport to tissue.
AB  - To improve understanding of microvascular O(2) transport, theoretical modeling
      has been pursued for many years. The large number of studies in this area attests
      to the complexities (i.e., biochemical, structural, and hemodynamic) involved.
      This article focuses on theoretical studies from the last two decades and, in
      particular, on models of O(2) transport to tissue by discrete microvessels. A
      brief discussion of intravascular O(2) transport is first given, highlighting the
      physiological importance of intravascular resistance to blood-tissue O(2)
      transfer. This is followed by a description of the Krogh tissue cylinder model of
      O(2) transport by a single capillary, which is shown to remain relevant in
      modified forms that relax many of the original biophysical assumptions. However,
      there are many geometric and hemodynamic complexities that require the
      consideration of microvascular arrays and networks. Multivessel models are
      discussed that have shown the physiological importance of heterogeneities in
      vessel spacing, O(2) supply, red blood cell flow path, as well as interactions
      between capillaries and arterioles. These realistic models require sophisticated
      methods for solving the governing partial differential equations, and a range of
      solution techniques are described. Finally, the issue of experimental validation
      of microvascular O(2) delivery models is discussed, and new directions in O(2)
      transport modeling are outlined.

PMID- 18608990
TI  - Chemokine signaling to lymphocyte integrins under shear flow.
AB  - The arrest of lymphocytes at target vascular sites depends on the rapid
      activation of their integrins by specialized endothelial chemokines. For over a
      decade, the mechanisms by which these chemokines trigger initial integrin
      mediated adhesiveness and subsequent adhesion strengthening and crawling over
      endothelial surfaces have been dissected in vitro using flow chamber setups.
      These studies revealed that lymph node chemokines and subsets of inflammatory
      chemokines, collectively termed "arrest chemokines," can trigger the fastest
      measurable inside-out integrin activation events. Recent studies indicate that
      shear forces applied on lymphocytes are instrumental in these rapid activation
      processes. Different GTPases have been implicated in these activation processes.
      As these enzymes contribute to successive integrin activation and redistribution
      processes in both early and prolonged contacts there is a growing need to dissect
      in vitro and validate in vivo specific signaling routes involved in early and
      late integrin activation events controlling lymphocyte arrest and their
      subsequent crawling to sites of diapedesis. In this article, we present an
      overview of both early and recent shear-flow studies of integrin activation in
      lymphocytes and discuss future perspectives of integrin activation research in
      vitro and in vivo.

PMID- 18608991
TI  - RBC aggregation: more important than RBC adhesion to endothelial cells as a
      determinant of in vivo blood flow in health and disease.
AB  - Although the shear-dependent and reversible phenomenon of red blood cell (RBC)
      aggregation has been studied for decades, its role as a determinant of in vivo
      blood flow in both health and disease has not yet been fully documented. In this
      brief review, we present compelling arguments, supported by literature evidence,
      that in vivo flow dynamics are more affected by RBC aggregation than by RBC
      adhesion to endothelial cells (ECs). A companion article (i.e., a "counter
      point") published in this issue of the journal argues that in disease states, RBC
      EC adhesion is the more important determinant.

PMID- 18608992
TI  - Nitric oxide bioavailability in the microcirculation: insights from mathematical
      models.
AB  - Over the last 30 years nitric oxide (NO) has emerged as a key signaling molecule
      involved in a number of physiological functions, including in the regulation of
      microcirculatory tone. Despite significant scientific contributions, fundamental
      questions about NO's role in the microcirculation remain unanswered. Mathematical
      modeling can assist in investigations of microcirculatory NO physiology and
      address experimental limitations in quantifying vascular NO concentrations. The
      number of mathematical models investigating the fate of NO in the vasculature has
      increased over the last few years, and new models are continuously emerging,
      incorporating an increasing level of complexity and detail. Models investigate
      mechanisms that affect NO availability in health and disease. They examine the
      significance of NO release from nonendothelial sources, the effect of transient
      release, and the complex interaction of NO with other substances, such as heme
      containing proteins and reactive oxygen species. Models are utilized to test and
      generate hypotheses for the mechanisms that regulate NO-dependent signaling in
      the microcirculation.

PMID- 18608996
TI  - The use of superelastic suture clips in laparoscopic gastric banding.
AB  - Nickel-Titanium suture clips have been developed to enhance suturing in
      cardiovascular surgery (U-CLIP), Medtronic, Minneapolis, MN, USA). The first
      applications of superelastic suture clips in bariatric surgery were reported by
      Barba and Kane in 2004. No other experiences in this field have been reported or
      published. Our experience with this newly developed suture clip, used for
      suturing the anterior wrap in laparoscopic gastric banding, started in 2007. The
      U-Clip technology and the surgical technique are described and discussed in this
      article.

PMID- 18608997
TI  - Circular 'superelastic' compression anastomosis: from the animal lab to clinical
      practice.
AB  - The recent development of a compression device using shape memory Nitinol
      technology to create an end-to-end anastomosis has renewed the interest in
      sutureless anastomotic techniques. A phase II, prospective open label clinical
      trial was started in May 2007 to evaluate the feasibility and safety of this new
      anastomotic device. Fourty patients who need left colectomy or high anterior
      resection for either diverticular disease or adenocarcinoma will be recruited in
      two academic hospitals (Uppsala,Sweden and Leuven, Belgium). Clinical leakage is
      the primary endpoint. Only preliminary results are available to date as the
      recruitment is ongoing. The median age of the first ten patients is 57.5 years
      (44-72). No anastomotic leakage occurred. The median hospital stay was 4.0 days.
      Only three patients noticed the passage of the ring through the anal canal. By
      three weeks no ring was sustained in the gastrointestinal tract as was
      objectified by plain X-ray. First clinical use of this new anastomotic device
      seems promising. Final results for the total phase II trial are awaited. A
      prospective randomized trial to compare the efficacy of the EndoCar 28 with
      conventional stapling should be the next step.

PMID- 18608998
TI  - Should cystoscopy be routinely performed after laparoscopy-assisted vaginal
      hysterectomy?
AB  - This study was undertaken to determine the usefulness of routine intra-operative
      cystoscopy in documenting ureteral patency after laparoscopy-assisted vaginal
      hysterectomy (LAVH). There were eighty patients who underwent LAVH for benign
      tumors of the uterus (adenomyosis and myoma), uterine prolapse, persistent
      intraepithelial neoplasm of the cervix (CIN3) and cervical carcinoma in situ
      (CIS). Intra-operative cystoscopy with ureteral stenting was performed at the
      time of LAVH to evaluate the urinary tract. From among the 80 patients who
      underwent LAVH, 52 had myoma, 19 had adenomyosis, six patients had uterine
      prolapse, one had CIS and seven patients were diagnosed to have CIN3. Cystoscopy
      discovered one unsuspected bladder injury. Hematuria was the immediate
      complication caused by intraoperative cystoscopy. It was observed in ten
      patients. Urinary tract evaluation, including cystoscopy and ureteral stenting at
      the time of complex gynecologic surgery such as LAVH could be incorporated in the
      whole surgical procedure. It decreases morbidity associated with unrecognized
      injury.

PMID- 18608999
TI  - How advances in tissue approximation technology and technique influence progress
      in minimally invasive therapy.

PMID- 18608994
TI  - Systems biology of vascular endothelial growth factors.
AB  - Several cytokine families have roles in the development, maintenance, and
      remodeling of the microcirculation. Of these, the vascular endothelial growth
      factor (VEGF) family is one of the best studied and one of the most complex. Five
      VEGF ligand genes and five cell-surface receptor genes are known in the human,
      and each of these may be transcribed as multiple splice isoforms to generate an
      extensive family of proteins, many of which are subject to further proteolytic
      processing. Using the VEGF family as an example, we describe the current
      knowledge of growth-factor expression, processing, and transport in vivo.
      Experimental studies and computational simulations are being used to measure and
      predict the activity of these molecules, and we describe avenues of research that
      seek to fill the remaining gaps in our understanding of VEGF family behavior.

PMID- 18609000
TI  - The current evidence on stapled versus hand-sewn anastomoses in the digestive
      tract.
AB  - The innovation process and developments in technology have given surgeons new
      products which can improve their performance and benefit our patients. Before the
      era of laparoscopic surgery one of the most important applications in surgical
      practice was the introduction of staplers. In this article, the evidence
      supporting the decision whether to use a mechanical device (stapler) or to make a
      hand-sewn anastomosis is presented. A sytematic review of the literature was
      performed. The search included published meta-anaylses, randomized clinical
      trials and comparative studies. Key words for the initial search were: surgical
      anastomosis, stapler, hand-sewn. There was no language restriction. The reference
      lists from the selected articles were also checked by the author. Literature data
      on main outcomes concerning the application of one or the other surgical
      technique have been analysed. The literature search yielded published data on
      various procedures in digestive surgery. Most of the available high-quality
      evidence was for gastric and colorectal resections. Resection of the esophagus,
      use of staplers in emergency procedures and some initial reports on pancreatic
      surgery were also retrieved. The evidence from the literature shows that stapler
      anastomoses take less operative time and are more costly than hand-sewn
      anastomoses. Regarding the morbidity and leaks rate the staplers give equal or
      better results when compared with the hand-sewn technique. Nevertheless, proper
      handling of staplers and experience remain crucial issues if one wants to gain
      benefits when using these devices.

PMID- 18609001
TI  - New concepts for a compression anastomosis: superelastic clips and rings.
AB  - Gastrointestinal anastomosis is a crucial step in many operative procedures, and
      responsible for a major portion of early and late post-operative complications.
      In order to improve on the results of current tools to perform an anastomosis,
      such as sutures and staplers, new concepts are being developed. One of these
      concepts is compression anastomosis. Compression anastomosis has been tried in
      the past but did not become popular mostly because of technical reasons.
      Recently, trials to accomplish compression anastomosis using Nitinol devices were
      conducted. Two devices were made and tested in the past three years: a side-to
      side device and an end-to-end device. The common principle in both devices is the
      compression of two bowel loops through the constant pressure of a Nitinol device,
      thus producing a dual process of necrosis and healing until the lumens of both
      bowels fuse, and the device falls into the lumen and is excreted. Both devices
      have been tested in animals and humans, with encouraging results. In animals, the
      anastomoses were shown to demonstrate minimal inflammation and no foreign body
      reaction, with perfect healing of the mucosa. The side-to-side device was tested
      in over 500 human patients, and the end-to-end device is currently used in a
      large, multi-centric human trial.

PMID- 18609002
TI  - Robotic suturing: technique and benefit in advanced laparoscopic surgery.
AB  - Suturing is one of the main tasks in advanced laparoscopic surgery, but limited
      degrees of freedom, 2D vision, fulcrum and pivoting effect make it difficult to
      perform. Robotic systems provide corresponding solutions as three-dimensional
      (3D) view, intuitive motion and additional degrees of freedom. This review
      evaluates these benefits for their impact on suturing in experimental and
      clinical studies. The Medline database was searched for "robot*, telemanipulat*
      and laparoscop*". A total of 1150 references were found and further limited to
      "suturing" for experimental evaluation, finding 89 references. All references
      were considered for information on robotic suturing in advanced laparoscopy.
      Further references were obtained through cross-referencing the bibliography cited
      in each work. In experimental studies current robotic systems have proven their
      superior suturing capabilities compared to conventional laparoscopic techniques,
      mainly attributed to 3D visualization and full seven degrees of freedom. In
      clinical studies these benefits have not yet been sufficiently reproduced.
      Robotic systems have to prove the benefits shown in experimental studies for
      suturing tasks in clinical applications. Robotic devices shorten the learning
      curve of laparoscopic procedures. Further clinical trials focusing on anastomosis
      time are needed to assess this question.

PMID- 18609003
TI  - Laparoscopic low rectal anastomosis using a new stapling device: early experience
      with the Contour stapler.
AB  - Rectal cancer was initially considered a contraindication for the laparoscopic
      approach to low rectal resection due to the greater difficulty of deep pelvic
      dissection, but several studies have demonstrated its potential clinical
      advantages. The currently accepted technique for this intervention includes total
      mesorectal excision, which entails complete dissection of the mesorectum followed
      by low transection of the rectum. The laparoscopic approach provides good
      visualization and magnification of the operative field, but transection of the
      rectum may be more difficult. This is illustrated by the conversion rate of
      around 15% in most series, mainly due to technical difficulties. Contour
      placement may overcome these difficulties. Two key points support the interest in
      the use of devices with the features of the Contour. First, the current feeling
      and evidence indicate that with presently available laparoscopic devices, the
      section of the low rectum in selected patients (males and mid-third rectal
      tumors) is often difficult. Secondly, although the Contour device was designed
      for open surgery, surgeons have the intuitive perception that it perfectly
      accomplishes the functions an ideal laparoscopic stapler should include. There is
      clearly a need for more appropriate laparoscopic instruments for low rectal
      transection. The Contour device could be considered a prototype because it meets
      the surgeon's requirements when operating on the low rectum, providing one shot,
      simultaneous sewing and cutting function and a symmetric rectum section. However,
      a number of technical modifications would enhance the utility of the instrument
      in this setting.

PMID- 18609004
TI  - Sound stimulus qualities and severe auditory neglect.
AB  - We report the case of a patient who developed severe left auditory neglect
      following a cerebral vascular accident with infarction of areas in the frontal,
      temporal, and parietal lobes of the right hemisphere. The severity of neglect was
      documented using pure tones, speech, and environmental stimuli, administered
      binaurally and dichotically. Acuity examination and unilateral presentation of
      stimuli allowed exclusion of primary hearing deficit. A dichotic word test was
      used to evaluate the effects of implicit and explicit cuing. Contrary to our
      expectations, implicit semantic cues did not attenuate the neglect, and explicit
      manipulation of sound volume, consisting of increasing the volume in the left ear
      while maintaining right ear volume at a minimum did not increase the perception
      of neglected stimuli on the left. Explicit commands to selectively attend to the
      left ear also failed to improve left ear perception. These findings suggest that
      some manifestations of auditory neglect are not affected by attributes of the
      sound stimulus. Furthermore, the finding that manipulation of sound volume had no
      influence on the neglect supports the hypothesis that sound volume is perceived
      by the brain as encoded information and not as a simple analogue representation
      of sound magnitude mediated by variance in the firing rate of neurons in the
      auditory nerve.

PMID- 18609006
TI  - Errorless learning of novel routes through a virtual town in people with acquired
      brain injury.
AB  - Impaired route learning is a common consequence of acquired brain injury (ABI)
      but has received little attention in the research literature. Errorless learning
      may be a method of facilitating the learning of routes but this is unclear as
      previous studies of errorless learning have focused mainly on verbal skills and
      the only previous study involving route learning was based upon a pencil and
      paper task. In the present study we therefore use virtual reality to explore the
      benefits of errorless learning for routes in an ecologically valid task. Twenty
      people with acquired brain injury learned two routes, of equivalent difficulty,
      around a virtual town based upon the city of Nice. For one route, full guidance
      was provided throughout the learning trials in an errorless learning paradigm;
      the other route was learned using a procedure that allowed for trial and error.
      Route recall following the errorless learning condition was significantly more
      accurate than recall after errorful learning. This suggests that the benefits of
      errorless over errorful learning in acquired brain injury rehabilitation extend
      beyond verbal learning tasks to the practical task of route memorisation.

PMID- 18609005
TI  - Neuropyschological profile of reversible cognitive impairment in a patient with a
      dural arteriovenous fistula.
AB  - OBJECTIVE AND IMPORTANCE: Patients with dural arteriovenous fistulas (dAVFs) may
      present with cognitive impairment secondary to venous hypertension or ischemia.
      CLINICAL PRESENTATION: We present a patient with a dAVF supplied by the posterior
      meningeal artery who presented with severe encephalopathy and imaging consistent
      with bilateral thalamic ischemia. RESULTS: Detailed pre-operative
      neuropsychological testing documented severe cognitive deficits across multiple
      domains, localizing diffusely in the cerebral cortex, beyond that which would be
      expected from purely thalamic involvement. Approximately 2 months following a
      combined endovascular and surgical repair, repeat neuropsychological testing
      documented a dramatic improvement in cognitive symptoms while MRI abnormalities
      in the thalami resolved. CONCLUSION: Detailed neuropsychological testing may be
      useful in patients presenting with dAVFs in order to identify cognitive
      impairment, which may be out of proportion to imaging findings. Recognition of
      dAVF-associated cognitive impairment may lead to more aggressive, timely
      treatment in patients with otherwise lower-risk lesions. This detailed testing
      can also provide a baseline in order to document cognitive recovery after fistula
      repair.

PMID- 18609007
TI  - Prominent and persistent loss of past awareness in amnesia: delusion, impaired
      consciousness or coping strategy?
AB  - Profound loss of awareness for the past in amnesia has implications for our
      understanding of memory and belief systems, and how they may become disrupted in
      neurological conditions. We report the case of CW, a professional musician who
      became severely amnesic in 1985 following herpes simplex viral encephalitis
      (HSVE) at the age of 46 years. For many years CW stated several times a day that
      he had just woken up. He frequently wrote this in his diary too. When shown
      examples of his diary entries or videos of himself playing or conducting music,
      he recognised both his handwriting and himself on the video screen but stated
      vehemently that he "was not conscious then". In a previous paper (Wilson,
      Baddeley, & Kapur 1995), it was suggested that this lack of awareness for the
      past was a delusion, defined as a strongly held belief in the face of
      contradictory evidence (rather than implying any kind of psychiatric disorder per
      se). As a contribution to the academic debate regarding theories of "self", in
      the present paper we will review this explanation of CW's state as it had been in
      those early years, and we will also consider two other possibilities - namely,
      that CW had suffered from a loss of "autobiographical self" or "extended
      consciousness" (see Damasio, 2000, pp. 198-199), and that his verbal reports
      simply reflected a form of coping strategy to help him deal with the limited
      evidence he had available in "declarative" memory.

PMID- 18609008
TI  - A longitudinal study of awareness of deficit after moderate to severe traumatic
      brain injury.
AB  - Lack of awareness of deficits is a common problem after traumatic brain injury
      (TBI), and is associated with worse functional outcome and poor compliance with
      rehabilitation. Little is known, however, about the course of awareness of
      deficits after TBI. Using a longitudinal design, we examined changes in self
      awareness between the subacute stage (about 45 days after injury) and one-year
      follow-up in a sample of 123 individuals with moderate to severe TBI. Awareness
      of deficits was operationalised as the discrepancy between patient and family
      ratings on the Awareness Questionnaire (AQ) and Patient Competency Rating Scale
      (PCRS). Compared to baseline, awareness was improved at one year, as evidenced by
      smaller discrepancy scores and stronger correlations between participant and
      family ratings. Changes in awareness were most pronounced for the
      behavioural/affective domain and least pronounced for the motor/sensory domain,
      which showed best agreement at baseline. Even at one year, participants rated
      themselves as higher functioning than did their relatives. Awareness at baseline
      and, for the AQ, time to follow commands, significantly predicted awareness at
      one year. These results suggest that awareness of deficits improves between the
      subacute and post-acute stages after TBI, and highlight the need for effective
      interventions for persons with impaired awareness and for flexible timing of
      rehabilitation efforts.

PMID- 18609009
TI  - Reliability and validity of two new instruments for measuring aspects of mental
      slowness in the daily lives of stroke patients.
AB  - The objective of the study was to examine psychometric characteristics of two
      measures related to mental slowness experienced after stroke: One measure is
      aimed at performance on tasks, the other is a questionnaire evaluating perceived
      consequences of mental slowness. A group of 37 stroke patients and 33 matched
      controls were studied. A subgroup of 10 patients and 22 controls was observed by
      two independent raters to determine inter-rater reliability, a subgroup of 18
      patients completed the questionnaire twice over a two-week interval to determine
      test-retest stability. Results showed that internal consistency was acceptable
      for the Mental Slowness Observation Test (Cronbach's alpha=.61 and .73) and good
      for the Mental Slowness Questionnaire (alpha=.91). For the Observation Test,
      correlations between the results of the two raters ranged between .77 and .99 and
      intra-class correlation coefficients were between .86 and .99. For the
      Questionnaire, correlations between two test occasions ranged between .85 and .90
      and intra-class correlation coefficients were between .91 and .95. Correlations
      of between .52 and .67 were found between the Observation Test and
      neuropsychological tasks for speed of information processing. The Questionnaire
      correlated most strongly with scores on tests for activities of daily living
      (ADL) functioning, and fatigue and depression (correlations ranged between .37
      and .63). It was concluded that the two new instruments offer reliable and valid
      methods for measuring limitations in daily activities related to mental slowness
      and some of the consequences of mental slowness in terms of sense of time
      pressure, fatigue, depressive complaints and independent ADL functioning.

PMID- 18609010
TI  - Mild traumatic brain injury and its sequelae: characterisation of divided
      attention deficits.
AB  - Deficits in divided attention occur after a mild traumatic brain injury (MTBI)
      but many extant tasks lack sensitivity for detecting subtle cognitive
      difficulties. We use the Test d'Attention Partagee Informatise (TAPI), a novel
      dual-task paradigm, to investigate the impact of MTBI on the ability to divide
      attention between two stimuli sources. Individuals with MTBI (n=37) were
      evaluated within the first week following head trauma and at three months post
      injury. A healthy control (HC) group (n=79) was also assessed. The primary
      outcome was reaction time and there were three different conditions that included
      visual target detection and auditory digit span tasks. Analyses utilised repeated
      measures ANOVA and ANCOVA models that adjusted for relevant variables including
      post-concussive and affective symptoms. Results indicated that at both baseline
      and follow-up, the MTBI group had significantly slower reaction time than the HC
      group. Also, both the MTBI and HC groups had slower reaction times as
      participants progressed through each of the more challenging TAPI conditions.
      This study supports the usefulness of this novel instrument and allows clinicians
      and researchers to assess for subtle divided attention deficits that may persist
      in those with MTBI even three months post-injury.

PMID- 18609011
TI  - Editorial.

PMID- 18609012
TI  - A biopsychosocial deconstruction of "personality change" following acquired brain
      injury.
AB  - The judgement of personality change following acquired brain injury (ABI) is a
      powerful subjective and social action, and has been shown to be associated with a
      range of serious psychosocial consequences. Traditional conceptualisations of
      personality change (e.g., Lishman, 1998) have largely derived from individualist
      concepts of personality (e.g., Eysenck, 1967). These assume a direct link between
      neurological damage and altered personhood, accounting predominantly for their
      judgements of change. This assumption is found as commonly in family accounts of
      change as in professional discourse. Recent studies and perspectives from the
      overlapping fields of social neuroscience, cognitive approaches to self and
      identity and psychosocial processes following ABI mount a serious challenge to
      this assumption. These collectively identify a range of direct and indirect
      factors that may influence the judgement or felt sense of change in personhood by
      survivors of ABI and their significant others. These perspectives are reviewed
      within a biopsychosocial framework: neurological and neuropsychological deficits,
      psychological mechanisms and psychosocial processes. Importantly, these
      perspectives are applied to generate a range of clinical interventions that were
      not identifiable within traditional conceptualisations of personality changes
      following ABI.

PMID- 18609013
TI  - Cognitive-behavioural intervention for depression after stroke: five single case
      studies on effects and feasibility.
AB  - The purpose of the study was to investigate whether or not a cognitive
      behavioural intervention for depression after stroke has an effect and is
      feasible. A single-subject quasi experimental design (SSED) was used with an AB
      design and follow-up. The participants were five first episode stroke patients
      attending outpatient rehabilitation in a rehabilitation centre in The
      Netherlands. Mood and quality of life were measured on four occasions over four
      weeks (baseline phase A). During the eight week intervention phase (B) a visual
      analogue measure of mood was administered three times a week. Immediately after
      the intervention, and one and three months later, the baseline measures were
      repeated. The intervention (phase B) was based on cognitive-behavioural
      principles: recognising negative thoughts and challenging them, learning
      principles of relaxation, and planning of pleasurable activities. Following
      intervention three patients reported they had improved, three patients reported a
      minor improvement in quality of life, and four patients reported a more positive
      mood. Three months later three patients reported fewer depressive symptoms. Both
      patients and therapist were positive about the intervention and three months
      later, in daily life, all patients still applied the strategies. It was concluded
      that despite some ambiguous results, it seems that the cognitive-behavioural
      intervention has an effect on patients' mood. The intervention was rated as
      feasible by both patients and therapists.

PMID- 18609014
TI  - Walking and wheelchair navigation in patients with left visual neglect.
AB  - Patients with neglect veer to one side when walking or driving a wheelchair,
      however there is a contradiction in the literature about the direction of this
      deviation. The study investigated the navigational trajectory of a sample of
      neglect patients of mixed mobility status in an ecological setting. Fifteen
      patients with left-sided neglect after right hemisphere stroke were recorded
      walking or driving a powered wheelchair along a stretch of corridor. Their
      position in the corridor and the number of collisions was recorded. The results
      showed that the patients' path was dependent on their mobility status: wheelchair
      patients with neglect consistently deviated to the left of the centre of the
      corridor and walking patients with neglect consistently deviated to the right. A
      further two ambulant patients with neglect were recorded both walking and using
      the wheelchair to determine whether the differences were task or patient
      dependent. These two patients also exhibited leftward deviation when driving the
      wheelchair, but a rightward deviation when walking. These results suggest that
      the direction of the deviation is task dependent. Further work will be required
      to identify what features of the two modes of navigation lead to this
      dissociation.

PMID- 18609015
TI  - Aerobic endurance exercise benefits memory and affect in young adults.
AB  - Exercise seems a simple and widely practised behaviour that activates molecular
      and cellular signalling cascades involved in various central nervous system
      processes. Despite impressive results obtained in animal studies, fitness
      interventions have produced less reliable effects in humans, particularly in
      young adults. In the present study we tested the hypothesis that an individually
      adapted exercise training consisting of three running sessions of 30 minutes per
      week for 6 weeks, has the potential to improve visuospatial and verbal memory,
      concentration performance, and affect in young and healthy adults. Twenty-eight
      students participated and underwent a graded fitness test to assess individual
      fitness. The experimental group took part in an aerobic running programme,
      whereas the control group were asked not to vary their everyday activities. We
      found a significant increase in visuospatial memory performance and a significant
      increase in positive affect on a .05 alpha level of significance. However, we
      observed no effects of running training on concentration performance and verbal
      memory. We conclude that physical activity can possibly serve as a means to
      improve positively valenced aspects of affect and benefit visuospatial but not
      verbal memory in young adults.

PMID- 18609016
TI  - Self-esteem as a predictor of psychological distress after severe acquired brain
      injury: an exploratory study.
AB  - This study explored the effects of severe acquired brain injury (ABI) on self
      esteem. A within-subjects design investigated 22 severe ABI survivors' self
      reported responses on measures of self-esteem, mood and awareness of deficit.
      Data on cognitive ability and awareness of degree of executive impairment were
      included in the analysis. Self-esteem was measured using Rosenberg's Self-Esteem
      Scale (Rosenberg) and psychological distress by the Hospital Anxiety and
      Depression Scale (HADS). Self-esteem was found to be consistent over a two-week
      interval. Participants reported that their self-esteem had suffered following ABI
      when contrasting their current self-esteem with their retrospective perceptions.
      Self-esteem was highly correlated with psychological distress. More intact
      cognitive functioning and awareness of deficit were associated with lower self
      esteem. The paradoxical finding that survivors who were more impaired cognitively
      and/or less aware of their deficits reported higher self-esteem poses an ethical
      dilemma for clinicians. It is hoped that this finding, along with the consistency
      of self-esteem ratings sparks further debate about how best to address issues of
      self-esteem among severe ABI survivors, particularly in the context of
      psychological distress, during rehabilitation.

PMID- 18609017
TI  - False selves in neuropsychological rehabilitation: the challenge of
      confabulation.
AB  - The presence of confabulation following brain damage can obstruct
      neuropsychological rehabilitation and management. A recent theoretical approach
      to confabulation emphasises that neurocognitive deficits are not sufficient to
      account for the content of confabulation. As a result, they are also insufficient
      to address the unique rehabilitation challenges that confabulation raises.
      Instead, confabulation could be best understood as the magnification of existing
      reconstructive memory processes, influenced by both neurocognitive and
      motivational factors. The paper reviews recent experimental findings showing that
      confabulations serve important functions of self-coherence and self-enhancement,
      despite their poor correspondence to reality. Case material is used to illustrate
      the meaningfulness of confabulation from the subjective perspective of the
      patient and to demonstrate that such a theoretical approach to confabulation can
      best inform management and rehabilitation efforts.

PMID- 18609019
TI  - Cognitive behaviour therapy for post-traumatic stress symptoms in the context of
      hydrocephalus: a single case.
AB  - There is limited information about anxiety disorders occurring in the context of
      the challenging condition of hydrocephalus. This paper describes the treatment,
      via trauma-focused cognitive behaviour therapy (TFCBT), of post-traumatic stress
      symptoms arising on account of hydrocephalus in a 23-year-old man. Specific
      components of the intervention included exposure, cognitive disputation, and
      relaxation training. The 20-session intervention appeared effective with
      decreases in anxiety (on the Hospital Anxiety and Depression Scale) and event
      impact (on the Impact of Events Scale) from clinical to sub-clinical levels. The
      main contributor to change appeared to be the exposure element of the treatment.
      The benefits of the intervention were maintained at one-, three-, and six-month
      follow-up.

PMID- 18609020
TI  - The reliability and validity of the PALOC-s: a post-acute level of consciousness
      scale for assessment of young patients with prolonged disturbed consciousness
      after brain injury.
AB  - The objective of the study was the validation of the Post-Acute Level of
      Consciousness scale (PALOC-s) for use in assessing levels of consciousness of
      severe brain injured patients in a vegetative state or in a minimally conscious
      state. A cohort of 44 successively admitted patients (between 2 and 25 years of
      age), who were treated in an early intensive neurorehabilitation programme, were
      included in the study. Each patient was examined, using the Western Neuro Sensory
      Stimulation Profile (WNSSP) and the Disability Rating Scale (DRS), once every two
      weeks resulting in 327 examinations (all videotaped). To determine the
      reliability of the PALOC-s, six observers rated one videotape of each patient.
      One of the observers rated the same tapes a second time, 3-4 months later.
      Validity was determined by correlating 100 ratings of one observer with the
      scores on the WNSSP and the DRS. To determine the responsiveness of the PALOC-s,
      the size of change between the scores of the first and last examinations was
      calculated. The inter-observer correlations and agreement scores varied between
      .82 and .95. The intra-observer correlation and agreement scores varied between
      .94 and .96. Correlations with the WNSSP varied between .88 and .93, and with the
      DRS between .75 and .88. The responsiveness was significantly high (t=8.2), with
      a standardised effect size of 1.30. It is concluded that the PALOC-s is a
      reliable, valid, and responsive observation instrument provided it is
      administered after a structured assessment by an experienced and trained
      clinician. The PALOC-s is feasible for use in clinical management, as well as in
      outcome research.

PMID- 18609021
TI  - An exploratory case study of the impact of ambient biographical displays on
      identity in a patient with Alzheimer's disease.
AB  - One of the most troubling symptoms of Alzheimer's disease is the loss of the
      patient's sense of identity. This loss complicates relationships, increases
      apathy, and generally impedes quality of life for the patient. We describe a
      novel in-home ambient display called Biography Theatre that cycles through music,
      photographs, movies, and narratives drawn from the patient's past and current
      life. We conducted an exploratory case study with an 84-year-old male with
      moderate-stage Alzheimer's disease (Mr H). The study consisted of three phases: a
      baseline phase, a phase wherein autobiographical materials were collected and
      discussed, and a phase wherein the display was deployed in the home. The patient
      demonstrated improvement on standardised tests of apathy and positive self
      identity, but did not improve on tests of autobiographical memory, anxiety,
      depression, and general cognition. We also report on caregiver reactions to the
      intervention and how the display helped them cope with and reinterpret their
      loved one's condition. This work suggests that interdisciplinary work involving
      "off the desktop" computing technologies may be a fruitful way to provide
      rehabilitative benefit for individuals with Alzheimer's disease.

PMID- 18609022
TI  - Functional electrical stimulation (FES) of the upper limb alleviates unilateral
      neglect: a case series analysis.
AB  - We report the results of a new form of therapy for unilateral spatial neglect.
      Functional electrical stimulation (FES) applied to the left forearm extensor
      muscles reduced the symptoms of severe left unilateral visual neglect in three
      patients, with the benefits being measurable at 6 months post-treatment. We
      suggest that FES activates a proprioceptive map within the right parietal lobe
      whose level of activation is otherwise diminished by the lesion. This both
      increases awareness of the contralesional side and stimulates functional
      interactions with the environment.

PMID- 18609023
TI  - Cognitive rehabilitation of the updating sub-component of working memory in
      schizophrenia: a case study.
AB  - Working memory problems have been identified as a core cognitive deficit in
      schizophrenia. In this paper, we present the results of a cognitive
      rehabilitation programme (Duval & Coyette, 2005) administered to a schizophrenia
      patient, and specifically designed to improve the updating sub-component of
      working memory. The original feature of this programme was that it involved two
      types of updating exercises: cognitive and ecological. The purpose was to enable
      the patient to acquire cognitive strategies that alleviate the mental load of the
      central executive and to transfer them to daily life. The specificity and
      efficacy of the programme were assessed with multiple (cognitive, ecological and
      non-target) baseline measurements. In addition, several questionnaires were
      administered to assess the effect of the programme on subjective cognitive
      complaints affecting daily life, psychiatric symptoms and self-esteem. The
      results demonstrated the efficacy of the rehabilitation programme on the updating
      function and the generalisation of these beneficial effects to daily life. A
      significant decrease in both subjective cognitive complaints and psychiatric
      symptoms was also observed. However, the patient's self-esteem did not improve.

PMID- 18609024
TI  - "Feeling part of things": personal construction of self after brain injury.
AB  - There is a growing body of literature on the nature of subjective changes
      experienced following brain injury. This study employs personal construct and
      qualitative research methods to address the question of how people make sense of,
      or construe, themselves after brain injury. Thirty-two individuals who had
      experienced acquired brain injury engaged in small group exercises based on a
      personal construct approach. Bipolar constructs were elicited through systematic
      comparison of pre-injury, current and ideal selves. The constructs elicited in
      this way were subjected to a thematic analysis. Nine themes were derived and an
      acceptable level of reliability of the definitions of these themes achieved. The
      highest proportion of constructs fell into the theme "experience of self in the
      world", followed by "basic skills" (cognitive, sensory, physical, social) and
      "experience of self in relation to self". It is concluded that following brain
      injury, people make sense of themselves in terms of the meanings and felt
      experiences of social and practical activity. This is consistent with social
      identity theory and stands in contrast to traditional neuropsychological sense
      making in terms of impairments and abilities alone, or activity or social
      participation alone. The implications of these findings for future research and
      rehabilitation are briefly considered.

PMID- 18609025
TI  - Every third patient in primary care suffers from depression, anxiety or alcohol
      problems.
AB  - The aims of the study were to explore the prevalence of patients with depression
      and anxiety in primary care, its co-occurrence with hazardous/harmful alcohol
      use, and its relation to gender, age and reason for visit. A questionnaire,
      including the self-rating Hospital Anxiety and Depression scale and the Alcohol
      Use Disorder Identification Test, was consecutively distributed to 1800 patients
      at 11 primary healthcare centres in the county of Vasterbotten, Sweden. The
      response rate was 77.3% (1392 patients), 38% men and 62% women. A total of 31.9%
      showed symptoms of depression and/or anxiety, with no gender differences.
      Harmful/hazardous alcohol use was found in 11.9% of the patients, 17.3% in men
      and 8.8% in women, although the region in Sweden has relatively low alcohol
      consumption among the population. Age was an important factor. Incidences of the
      conditions often occurred simultaneously. About half (51%) of those with
      harmful/hazardous alcohol use also showed symptoms of depression and/or anxiety.
      The most common causes for patients with symptoms of depression, anxiety or risk
      consumption of alcohol to seek care were the same as for the general population,
      namely complaints of pain or infection. Only 7.8% visited the primary care for
      psychiatric reasons, according to their own given reasons. In all, 38% of the
      patients showed signs of psychiatric symptoms and/or alcohol problems or a
      combination of these. The fact that every third patient showed symptoms of
      depression, anxiety and/or alcohol problems underlines the strategic position for
      early identification, intervention and treatment within primary healthcare.

PMID- 18609026
TI  - Abstinence, occasional drinking and binge drinking in middle-aged women. The
      Women's Health in Lund Area (WHILA) Study.
AB  - Although drinking patterns in women have received increased attention, few
      studies have focused on middle-aged women. Drinking patterns were investigated in
      a population sample of 513 Swedish women aged 50-59, and analysed in relation to
      social situation, and mental and physical health. The chi-square test was used to
      analyse differences in proportions. Variables showing significant differences
      were entered into a multivariate or multinomial logistic regression model.
      Abstainers and occasional drinkers had lower levels of education and more often
      regular medical control compared with weekly drinkers. Furthermore, abstainers
      more often had disability pension. Among women drinking alcohol, 56.6% affirmed
      binge drinking within the last year and 39.4% within the last month. Binge
      drinkers did not differ in terms of social situation, mental or physical health,
      compared with other drinkers. Drinking to relieve tension was affirmed by 7.2%.
      These women had more mental symptoms and less contact with friends compared with
      other drinkers; furthermore, they were more often binge drinkers. Binge drinking
      was common and health and social consequences of this drinking pattern in middle
      aged women need to be further explored. Women drinking to relieve tension may
      need intervention for both drinking habits and mental health.

PMID- 18609027
TI  - A follow-up of elderly depressed patients.
AB  - The study aims to establish the predictive value of a diagnosis of depression
      among elderly according to the 10th revision of the International Statistical
      Classification of Diseases (ICD-10) by measuring morbidity, medication usage,
      health service utilization and mortality during an 8-year follow-up of depressed
      elderly inpatients (n=76) and community-living depressed patients (n=38) compared
      with controls (n=116). The data were taken from GPs' medical records and health
      statistics registers. At baseline, no significant differences were observed
      between the two cohorts of depressed patients and the controls in terms of
      prevalence of cardiovascular, respiratory or cerebrovascular morbidity. During
      follow-up, both cohorts of depressed patients had significantly increased rates
      of recurrent depressions, consumption of antidepressants, psychiatric in- and
      outpatient admissions, and home visits; inpatients used more psychiatric hospital
      days. Health service utilization in somatic hospitals and somatic diagnoses was
      not significantly increased. Inpatients used significantly fewer GP office-hour
      services but more out-of-hours services than the control group. Community-living
      depressed patients experienced no significant increase in use of GP services.
      Survival was unaffected in both cohorts. In agreement with other studies,
      especially inpatient depression predicted increased rates of recurrent
      depressions and increased use of psychiatric hospital services, indicating poor
      long-term outcome. Inpatients consumed fewer GP office-hour services but more out
      of-hours services, possibly due to less office-hour contact. Contrasting with
      other studies, ICD-10 depression among elderly predicted no increase in the use
      of somatic hospital facilities.

PMID- 18609028
TI  - Attitudes towards mental disorders and psychiatric treatment--changes over time
      in a Swedish population.
AB  - Over the years a lot of research of attitudes towards mental disorders, towards
      people with mental illness and towards psychiatric services and treatment have
      shown a persistent negative attitude. There are, however, few studies on changes
      over time. The aim of this study was to compare responses to a questionnaire on
      attitudes towards mental disorders and psychiatric patients and the perception of
      psychiatric treatment in a community in northern Sweden in 1976 and 2003. In 1976
      a random sample of 391 persons 18-70 years of age were asked and in 2003 a new
      sample of 500 persons from the same community were approached with the same
      questions. There are considerable changes over time. In 2003, almost 90% agree to
      the statement that mental illness harms the reputation more than physical
      illness, compared with 50% in 1976. In 2003, 51% agreed to the statement "Most
      people with mental disorders commit violent acts more than others" compared with
      24% in 1976. There is an apparent ambivalence towards psychiatric treatment.
      Whilst 88% would advice a person with mental problems to contact a psychiatrist,
      still 26% would not like themselves to be referred to a psychiatrist. We argue
      that improving treatment methods is as important as changing attitudes through
      accurate information.

PMID- 18609029
TI  - The Strengths and Difficulties Questionnaire as a screening instrument in a
      community sample of high school seniors in Sweden.
AB  - The Strengths and Difficulties Questionnaire (SDQ) has been used among Swedish
      children since 1996, usually the parent or the teacher version. The self-report
      version was originally developed for children aged 11-16 years. The aim of this
      study was to investigate the application of the Swedish self-report version to a
      representative sample of 1015 senior high school students aged 17-19 years. Girls
      reported more emotional symptoms and scored higher on prosocial items than boys.
      Boys on the other hand scored higher on both conduct and peer problems. The means
      were similar to means in two Nordic studies that have included subjects of this
      age group. A confirmatory five-factor analyses explained 44.5% of the variance
      with a good fit for all subjects and boys but somewhat weaker for girls. The item
      subscale correlation (ISC) ranged from moderate to high (r=0.47-0.76) and the
      Cronbach's alpha was 0.74 (ranging in the five subscales 0.50-0.70). The SDQ
      seems to be useful even in this older age group. The psychometric qualities were
      acceptable but can probably be improved by changing the oppositely worded
      questions and by considering development of different questionnaires for boys and
      girls at least in late adolescence.

PMID- 18609030
TI  - Lack of psychopathic character (Rorschach)  in forensic psychiatric rapists.
AB  - Previous research using Rorschach is sparse in rapists. The aim of this study of
      10 violent male forensic psychiatric rapists was to describe them on a set of
      Rorschach variables, which are assumed to reflect psychopathic character, in
      order to increase our understanding of rapists. The participants were involved in
      a long-term psychodynamic sexual offender treatment program. They were previously
      assessed on dyslexia and ADHD, and the results showed an over-representation of
      these disorders in this sample. Compared with normative samples, the participants
      scored significantly lower on three of the Rorschach variables--Lambda, WSum6 and
      Afr. The participants did not meet criteria for psychopathic character. Although
      the generalization of the results from 10 rapists is severely limited, our
      results suggest helplessness in managing emotionally laden situations and hint at
      the problems experienced by this sample of forensic psychiatric rapists.
      Clinicians should be aware of the lack of psychopathic character in some rapists
      and that effective treatment programs should focus on training this type of
      rapists to be able to react appropriately to emotional stimuli.

PMID- 18609031
TI  - The validity of schizophrenia diagnosis in the Finnish Hospital Discharge
      Register: findings from a 10-year birth cohort sample.
AB  - The purpose of this study was to investigate the diagnostic validity of
      schizophrenia in the Finnish Hospital Discharge Register (FHDR) with a large,
      epidemiologically representative sample using a multidiagnostic approach (DSM-III
      R, DSM-IV, ICD-10), and to find additional criteria that could be used to improve
      the validity of schizophrenia diagnosis in future register-based research that
      utilizes the FHDR. The study population consisted of all individuals (n=877) who
      were born in Helsinki, Finland, between 1 January 1951 and 31 December 1960, and
      who had had at least one diagnosis of schizophrenia, schizophreniform disorder or
      schizoaffective disorder in the FHDR. All their available hospital case notes
      were collected. The total number of subjects for whom case notes were obtained
      was 806. We used the OPCRIT system (version 3.4) to produce diagnoses according
      to ICD-10, DSM-III-R and DSM-IV criteria based on the information extracted from
      the hospital case notes. We examined the distribution of the DSM-III-R, DSM-IV
      and ICD-10 diagnoses generated by the OPCRIT and calculated the proportion of
      individuals who received the same diagnosis in the FHDR and in the OPCRIT
      assessment. The proportion of subjects who received a core schizophrenia spectrum
      diagnosis (schizophrenia, schizoaffective disorder or schizophreniform disorder)
      in both the FHDR and OPCRIT assessment varied between 75% (DSM-III-R criteria)
      and 78% (ICD-10 criteria). Of the subjects with a narrow schizophrenia diagnosis
      in the FHDR, between 74% (DSM-IV) and 78% (ICD-10) received a diagnosis of
      schizophrenia in the reassessment depending on the diagnostic criteria applied.
      Eighty per cent of those who had received a core schizophrenia spectrum FHDR
      diagnosis after 1982 (vs. 56% of those who had received their last schizophrenia
      diagnosis in 1982 or before) received a DSM-IV diagnosis of core schizophrenia
      spectrum disorder. Of the 58 subjects in the sample who had been given at various
      times diagnoses of both core schizophrenia diagnosis and bipolar I diagnosis in
      FHDR, 43% received a core schizophrenia spectrum diagnosis according to DSM-IV
      criteria. The validity of the FHDR schizophrenia diagnosis is acceptable for
      large-scale register studies and comparable with that of other Nordic registers.
      Diagnostic validity can be further improved by selecting subjects who have core
      schizophrenia spectrum disorder as the latest diagnosis, by omitting cases
      diagnosed before 1982, and by excluding cases with a register diagnoses of both a
      core schizophrenia spectrum and bipolar I disorder.

PMID- 18609032
TI  - A latent class analysis of adolescent adverse life events based on a Danish
      national youth probability sample.
AB  - The aim of this study was to determine if there are meaningful clusters of
      individuals with similar experiences of adverse life events in a nationally
      representative sample of Danish adolescents. Latent class analysis (LCA) was used
      to identify such clusters or latent classes. In addition, the relationships
      between the latent classes and living arrangements and diagnosis of post
      traumatic stress disorder (PTSD) were estimated. A four-class solution was found
      to be the best description of multiple adverse life events, and the classes were
      labelled "Low Risk", "Intermediate Risk", "Pregnancy" and "High Risk". Compared
      with the Low Risk class, the other classes were found to be significantly more
      likely to have a diagnosis PTSD and live with only one parent. This paper
      demonstrated how trauma research can focus on the individual as the unit of
      analysis rather than traumatic events.

PMID- 18609033
TI  - Study of the pressures applied by a Cheneau brace for correction of adolescent
      idiopathic scoliosis.
AB  - We performed a study on 32 idiopathic scoliotic patients (30 females, 2 males)
      treated with a Cheneau brace. Eighteen patients had a single right thoracic curve
      and 14 had a single right thoracolumbar curve. We used the TekScan system
      (ClinSeat Type 5315 Sensor, TekScan, Boston MA, USA) to measure pressures at the
      skin-brace interface, assess the effect of strap tension and analyze the
      variation of these pressures with position and activity. The TekScan device
      enabled identification of the pressure areas corresponding to the brace's three
      loading points. The pressure under the main pad had a greater mean value than the
      pressure under the two counter-pads. Tightening the straps led to a significant
      increase in the pressures, whatever the position studied or the curve pattern.
      Compared with the standing (reference) position, we observed significantly higher
      pressures during maximal inspiration (p < 0.001) and lower pressures during
      maximal expiration, in the prone position and after having risen from a lying
      position, for both thoracic curves (p < 0.001) and thoracolumbar curves (p <
      0.01). The pressures for thoracolumbar curves were lower than those for thoracic
      curves, whatever the position studied and both before and after strap adjustment.
      For lying positions, lying on the right side produced the greatest increase
      pressure. Even though the TekScan system does not provide direct information on
      the correction of spinal curvature, it appears to be a useful tool in the
      treatment of scoliotic patients. Strap adjustment clearly influences the applied
      pressures - particularly those on the rib cage. During activity, there is a
      natural tendency to decrease the pressure; this justifies efforts to maintain
      strap tensions in general and during day wear in particular.

PMID- 18609034
TI  - Moving social boundaries.

PMID- 18609035
TI  - Moving beyond Disability.
AB  - Moving beyond Disability was the theme of the 12th World Congress of the
      International Society for Prosthetics and Orthotics. This paper is a reflection
      of one of the keynote lectures discussing the International Classification of
      Functioning, Disability and Health (ICF). Multicultural aspects in disability and
      sexuality in amputees will be discussed within the ICF perspective. Finally,
      Internet and research in the light of having a disability are positioned within
      the theme.

PMID- 18609036
TI  - Moving the profession.

PMID- 18609037
TI  - Challenges of CPD for physiotherapists working as lone practitioners in amputee
      rehabilitation.
AB  - OBJECTIVES: The aim of this study was to explore the issues around continuing
      professional development (CPD) for physiotherapists working as lone practitioners
      in amputee rehabilitation in the United Kingdom (UK). DESIGN: Qualitative method
      using a phenomenological approach via one to one semi-structured interviews and
      thematic data analysis. SETTING AND PARTICIPANTS: Ten physiotherapists with
      responsibility for amputee rehabilitation working as lone practitioners in
      hospitals or specialist centres in the UK. RESULTS: CPD is valued and there is
      commitment towards the process. Current solutions are identified but there are
      frustrations around more structured CPD and organizational issues. These include
      inadequate access to learning opportunities, lack of professional feedback,
      insufficient time and limited learning skills. CONCLUSION: There are
      opportunities for improving CPD through organizational structures but specialist
      input is recommended to support lone practitioners and managers with the process,
      e.g., consultant or peripatetic therapists.

PMID- 18609038
TI  - A welcome message to the International Society for Prosthetics & Orthotics from
      the World Health Organization.

PMID- 18609039
TI  - Re-defining self after limb loss: a psychological perspective.
AB  - The loss of a limb is a traumatic and far-reaching event and often represents a
      struggle for survival, psychosocial adaptation and re-defining of self. In this
      case study presentation, a patient's relationship with disability is explored by
      means of a comprehensive model in understanding and assessing the trauma journey.
      The value of projective techniques and narrative therapy will be highlighted in
      the process of re-defining self. It is hoped that professionals working with
      patients with limb loss will be able to intervene constructively and engage in
      taking-it-back practices.

PMID- 18609040
TI  - The kinetics of lipid micro-emboli during cardiac surgery studied in a porcine
      model.
AB  - OBJECTIVE: To study the kinetics of lipid micro-emboli during cardiac surgery.
      DESIGN: Eleven pigs were studied. Seven of these were put on extracorporeal
      circulation. A shed blood phantom consisted of blood, saline and radioactive
      triolein was added to the circuit. Both venous and arterial blood samples were
      taken at short intervals. Four animals were used to study renal kinetics without
      extracorporeal circulation. The same kind of shed blood phantom was infused into
      the ascending aorta. Samples were taken from the renal artery and vein. All
      samples were analyzed for radioactivity by scintillation counting. RESULTS: A
      median 130-fold increase in radioactivity was seen in the blood and was quickly
      eliminated. Systemic first-pass wedging was found to be 62%. The first-pass
      elimination in the kidney was 77%. No radioactivity was found in urine.
      CONCLUSIONS: This study shows that the turnover of lipid micro-emboli is fast,
      and that the majority of the emboli are trapped on their first passage through
      the capillary system. No evidence was found of a renal excretion of these lipid
      emboli.

PMID- 18609042
TI  - Diastolic function and BNP changes during exercise predict oxygen consumption in
      chronic heart failure patients.
AB  - B-type natriuretic peptide (BNP) is a diagnostic and prognostic marker in heart
      failure (CHF) patients. AIM: To assess the relation between BNP, diastolic
      function and exercise capacity in CHF patients. METHODS: Fifty CHF patients
      underwent cardiopulmonary exercise testing. BNP levels were determined at
      baseline and at peak exercise. Patients were divided in two groups: with lower
      (<14 ml/kg/min) or higher (>or=14 ml/kg/min) peak oxygen consumption (VO(2)).
      RESULTS: Seventeen patients with lower peak VO(2) showed larger incidence of
      restrictive pattern of the transmitral flow (7/17 vs 4/33, p =0.036). E/Ea ratio
      was inversely related with peak VO(2) (r =-0.419, p =0.004) and directly related
      with BNP levels at baseline (r =0.449, p =0.001) and at peak exercise (r =0.475,
      p =0.001). LV ejection fraction was similar in the two groups. Independent
      predictors of exercise tolerance were E/Ea ratio (p =0.003), lg BNP at baseline
      (p =0.034) and increase in lg BNP during exercise (p =0.038). CONCLUSIONS: In CHF
      patients, E/Ea ratio is a predictor of exercise tolerance and is related with BNP
      level at rest and at peak exercise.

PMID- 18609043
TI  - Elevated glycosylated haemoglobin (HbA1c) is a risk marker in   coronary artery
      bypass surgery.
AB  - OBJECTIVE: To evaluate if glycosylated haemoglobin 1 (HbA1c) was associated with
      increased risk of infection and mortality after coronary artery bypass grafting
      (CABG). DESIGN: Prospective observational study. Preoperative HbA1c
      concentrations were correlated to outcome in patients followed for an average of
      3.5 years after CABG. RESULTS: HbA1c was > or =6% in 68% of 161 patients with
      diabetes mellitus (DM) and in 3% of 444 patients without DM. Superficial sternal
      wound infection was observed in 13.9% if HbA1c > or =6% versus in 5.5% if <6%
      (p=0.007). Mediastinitis occurred in 4.9% if HbA1c > or =6% and in 2.1% if HbA1c
      <6% (p=0.20) (Hazard ratio (HR) 1.9, 95% CI 0.6-5.9). Follow-up mortality was
      18.9% in patients with HbA1c > or =6% compared to 4.1% if HbA1c <6% (p<0.001)
      with HR 5.4, (95% CI 3.0-10.0) after multivariable adjustment. The risk of death
      was similar regardless of DM diagnosis. CONCLUSIONS: HbA1c > or =6% was
      associated with an increased risk of postoperative superficial sternal wound
      infections and a trend for higher mediastinitis rate and significantly higher
      mortality three years after CABG.

PMID- 18609044
TI  - No touch vein harvesting technique for CABG improves the long-term clinical
      outcome.
AB  - OBJECTIVES: To investigate the long-term clinical outcome, averaging 8.5 years,
      of two saphenous vein harvesting techniques for CABG; no touch (NT) versus
      conventional (C). DESIGN: In a randomized study, 49/52 in group NT and 44/52 in
      group conventional were evaluated for reangina, myocardial infarction, new
      revascularization, functional class, risk factors and medical treatment. The vein
      grafts and the native coronary arteries were correlated to the occurrence of
      reangina. RESULTS: There were significantly more patients free from angina and in
      NYHA class I (67.3 versus 43.2%; p =0.02) in group NT compared to group C. No
      cardiac death was found in group NT versus three in group C. There were trends
      towards fewer patients with cardiac death or myocardial infarction (3.8 vs.
      13.4%; p =0.16), more patients free from angina (75.5 vs. 63.6%; p =0.26) and
      fewer patients with graft occlusion (24.3 vs. 43.2% (p =0.14) in group NT.
      CONCLUSIONS: The results of the NT-technique are encouraging with no cardiac
      deaths, significantly more asymptomatic patients and a trend towards impact on
      hard clinical endpoints compared to the conventional technique.

PMID- 18609045
TI  - Surgical handling of saphenous vein grafts induces expression of matrix
      metalloproteinase 9.
AB  - OBJECTIVES: To investigate whether human veins responded to surgical handling
      with acute remodelling by measuring matrix metalloproteinase 9 (MMP9) expression
      and activity. DESIGN: Saphenous veins were collected from 24 patients (12 stable
      angina, 12 unstable angina) undergoing coronary artery bypass grafting.
      Expression of MMP9 and its regulators (plasminogen activators, plasminogen
      activator inhibitor-1, tissue inhibitor of metalloproteinase-1) was evaluated by
      semiquantitative RT-PCR in veins sampled at the start of and after surgical
      preparation, while protein was detected by western blotting. The proteolytic
      activity of MMP9 was analyzed by zymography. RESULTS: Gene (p=0.01) and protein
      (p=0.001) expression of MMP9 increased after surgical manipulation of vein grafts
      in all patients, accompanied by increased pro-MMP9 (p=0.04), but not active MMP9
      (p=0.6). Grafts from stable patients had increased gene (p=0.05) and protein
      (p=0.006) expression, as well as increased pro- (p=0.04) and active (p=0.04)
      MMP9. Grafts from unstable patients increased only in MMP9 protein expression
      (p=0.05). The MMP9 regulators were unchanged. CONCLUSIONS: Surgical handling of
      vein grafts increased expression and activity of MMP9. However, the surgery
      induced increase was attenuated in veins from unstable patients.

PMID- 18609046
TI  - Improved long-term survival following infrarenal abdominal aortic aneurysm
      repair.
AB  - BACKGROUND: The aim was to investigate early and long-term results following AAA
      repair during a 20-year period. METHOD: One thousand and forty one patients with
      AAA were treated with open surgery (905) or EVAR (136) during the period 1983
      2002. Comorbidity and factors influencing early and long-term results were
      investigated. Data were collected retrospectively from the patients' medical
      records. A complete follow-up was obtained. RESULTS: Women had a significantly
      higher 30-day mortality following repair of ruptured AAA than men. The degree of
      emergency, advancing age and renal failure were significantly associated with 30
      day mortality. We observed an improvement in long-term survival during the study
      period. Time interval of surgery, cerebrovascular disease, diabetes, COPD and
      renal failure influenced long-term survival negatively. CONCLUSION: Women with
      ruptured AAA have a higher early mortality than men, which needs to be
      investigated further. Long-term survival has improved during the study period.
      Age, diabetes, chronic obstructive pulmonary disease, renal failure and
      cerebrovascular insufficiency influenced the long-term survival negatively. EVAR
      is used to an increasing extent and the results are improving.

PMID- 18609047
TI  - Hemodynamics at rest do not match clinical improvement after surgical ventricular
      restoration.
AB  - OBJECTIVES: The aim was to study the change in cardiac index (CI) and pulmonary
      artery pressure (PAP) by intra-cardiac measurements after surgical ventricular
      restoration (SVR) in patients with left ventricular aneurysm and symptoms of
      heart failure. Aspects of functional improvement were analyzed as secondary
      outcomes. DESIGN: Mean PAP and CI were obtained before and 6 months
      postoperatively in 22 patients who underwent SVR. RESULTS: There were no
      significant changes in CI (2.3 vs. 2.4 L/min/m(2); p=0.91) or mean PAP (22 vs. 22
      mmHg; p=0.64) at rest before and six months after surgery. Left ventricular
      ejection fraction improved from 25 to 38% (p<0.001). Before surgery 15 patients
      (68%) were in NYHA class III-IV and 6 months after the operation 19 (86%)
      patients were in NYHA class I-II (p<0.001). CONCLUSIONS: Invasive hemodynamic
      measurements under resting conditions do not correspond well to the significant
      clinical improvement noted in these patients. Studies during exercise conditions
      are necessary to further evaluate this procedure.

PMID- 18609048
TI  - Regenerative capacity of intravenous autologous, allogeneic and human mesenchymal
      stem cells in the infarcted pig myocardium-complicated by myocardial tumor
      formation.
AB  - OBJECTIVES: Intravenous delivery of mesenchymal stem cells (MSCs) is an
      attractive approach for regeneration of infarcted myocardium. However, its
      efficacy is not well-defined in large animals. METHODS: Pigs (n =8) received
      intravenously autologous, allogeneic porcine or human MSCs (1 x 10(6) per kg
      bodyweight) labeled with fluorescent dye 48 hours post proximal LAD occlusion.
      Infarct size, histology and myocardial function were assessed 4 weeks later.
      RESULTS: Labeled MSCs migrated in the peri-infarct region resulting in improved
      myocardial function. Infarct size was larger in the control group (32+/-7%)
      compared to autologous (19+/-7%, p =0.008), allogeneic (24+/-4%, p =0.01) and
      human MSCs (26+/-5%, p =0.03). Fractional area shortening significantly increased
      after 4 weeks in pigs receiving autologous MSCs (34+/-7%, p =0.001), allogeneic
      MSCs (28+/-2%, p =0.004) and human MSCs (24+/-5%, p =0.027), but was lower in the
      control group (23+/-3%, n.s.). However, substantial callus formation and a non
      malignant cardiac "tumor" containing mesenchymal tissue was observed in one
      animal treated with human MSCs. CONCLUSIONS: Intravenously administered MSCs
      prevent pathologic remodeling and scar formation but bare potential risks from
      inflammatory-related products.

PMID- 18609049
TI  - End of the road for the diet-heart theory?
AB  - A personal account of the diet-cholesterol-heart hypothesis during the last sixty
      years, from its start with Jeremiah Stamler and Ancel Keys, its rapid rise and
      progressive fall during the last years. It is pointed out that the clinical
      picture of a heart attack is not synonymous with atherosclerotic changes in the
      coronary arteries. Special emphasis is given to the repeat publication of the
      results with the MRFIT screenees that have been used to obscure the negative
      results of the randomized multifactorial trials MRFIT in the US and The
      Gothenburg preventive trial in Sweden. A part addresses the treatment or
      prevention of CHD with medicines, where the mode of action and side-effects of
      the statin group of medicines have been more or less been neglected in the large
      amount of clinical trials. A better analysis of these features of the family of
      statins has to be done in order to limit their use to patients who really need
      them.

PMID- 18609050
TI  - Perioperative plasma brain natriuretic peptide and cardiotrophin-1 in off-pump
      coronary artery bypass.
AB  - OBJECTIVE: It has been suggested that brain natriuretic peptide (BNP) and
      cardiotrophin-1 (CT-1) are associated with myocardial dysfunction. The present
      prospective study was designed to investigate perioperative changes of plasma
      levels of BNP and CT-1 in off-pump coronary artery bypass (OPCAB). METHOD: Forty
      nine patients undergoing elective OPCAB were divided into three groups. Group I:
      no previous myocardial infarction; Group II: previous myocardial infarction more
      than 12 weeks; Group III: recent myocardial infarction within 4-8 weeks.
      Perioperative BNP and CT-1 levels were measured, and hematochemical parameters
      were also collected. RESULTS: Higher preoperative BNP and CT-1 levels were found
      in group III as compared to those in group I. BNP levels increased after
      operation, and reached peak value at 3-7 days after the operation. However, the
      postoperative changes of BNP levels were not different among groups in any time
      points. CT-1 levels did not change significantly after the operation as compared
      to baseline. CONCLUSION: Higher BNP and CT-1 levels were associated with recent
      myocardial infarction. BNP elevated after OPCAB, but CT-1 showed no significant
      postoperative changes. Postoperative changes of BNP and CT-1 do not associated
      with cardiac function in OPCAB.

PMID- 18609051
TI  - Liberal versus restricted fluid prescription in stabilised patients with chronic
      heart failure: result of a randomised cross-over study of the effects on health
      related quality of life, physical capacity, thirst and morbidity.
AB  - OBJECTIVE: To compare the effects of a restrictive versus a liberal fluid
      prescription, on quality of life, physical capacity, thirst and hospital
      admissions, in patients who had improved from NYHA class (III-)IV CHF to a stable
      condition without clinical signs of significant fluid overload. DESIGN: The
      present study is a randomised cross-over study. Seventy-four patients (mean age
      70+/-10 years, 16% women) -- with mild-moderate CHF -- were randomised 1:1 to
      either of two 16-week interventions. Intervention 1 prescribed a maximum fluid
      intake of 1.5 L/day. Intervention 2 prescribed a maximum fluid intake of 30-35
      ml/kg body weight/day. Sixty-five patients completed the study. RESULTS: There
      were no significant between-intervention differences in end-of-intervention
      quality of life, physical capacity or hospitalisation. However, there was a
      significant favourable effect on thirst and less difficulties to adhere to the
      fluid prescription during the liberal fluid prescription intervention.
      CONCLUSION: The results from this study indicate that it may be beneficial and
      safe to recommend a liberal fluid prescription, based on body weight, in
      stabilised CHF patients. These results warrant further investigation of the
      effects of fluid advice in CHF.

PMID- 18609052
TI  - Grade of left main coronary artery stenosis does not influence long-term
      mortality after coronary artery bypass surgery.
AB  - OBJECTIVE: To assess if grade of left main coronary artery (LMCA) stenosis
      influences early or long-term mortality after coronary artery bypass grafting
      (CABG). DESIGN: Among all 1 384 patients with LMCA stenosis at Karolinska
      Hospital, Stockholm, Sweden during 1990-1999, 131 deaths occurred within 5 years
      of surgery (cases). Matched controls (n=146) were randomly selected from all
      surviving LMCA patients taking gender, age and year of surgery into account.
      Angiographies were classified for grade of LMCA stenosis before the operation.
      RESULTS: High-grade LMCA stenosis was equally common among cases and controls (50
      vs. 45%). The odds ratio (OR) of mortality 5 years after the operation in
      patients with high-grade versus low-grade LMCA stenosis based on the matched
      pairs was 1.2 (95% confidence interval (CI) 0.7-2.0) and after multivariable
      adjustment using information on all subjects the OR was 1.0 (95% CI 0.6-1.7). For
      early and one year mortality similar odds ratios were observed but with wide
      confidence intervals. CONCLUSIONS: Grade of LMCA stenosis does not appear to
      influence early or long-term mortality after CABG performed during 1990-1999.

PMID- 18609053
TI  - Lipid lowering treatment patterns and goal attainment in Nordic patients with
      hyperlipidemia.
AB  - OBJECTIVES: Observational studies and surveys have shown that lipid-lowering
      treatment is not optimal neither with regard to number of patients treated nor
      with number of patients achieving recommended goals. To address this issue in the
      Nordic countries, we evaluated the published literature on lipid-lowering
      therapies in preventive cardiology in this region. DESIGN: Nordic papers
      published from 2000 throughout 2006 dealing with lipid-lowering management in
      coronary heart disease prevention were identified. In total, 19 studies were
      analyzed. RESULTS: Approximately half of the patients are inadequately treated
      and have not achieved recommended treatment goals of total cholesterol <5.0 and
      LDL-cholesterol <3.0 mmol/L. Statins were prescribed most often in low or medium
      doses. The predictive factors for treatment were cholesterol level, risk of
      cardiovascular disease, previous cardiovascular disease, age, and gender.
      CONCLUSIONS: There is a considerable need to improve standards of preventive
      cardiology. Statins have to be given evidence based to achieve treatment goals
      according to lipid levels, and higher doses of statins or combination therapy
      with a statin and a cholesterol absorption inhibitor or niacin is often needed.

PMID- 18609054
TI  - Refractory angina pectoris carries a favourable prognosis: a three-year follow-up
      of 150 patients.
AB  - OBJECTIVE: To investigate the three-year prognosis in refractory angina pectoris.
      PATIENTS: Two hundred and forty three patients were screened at six European
      university hospitals for a gene therapy trial. In 150 patients refractory angina
      pectoris could be confirmed. Vital status was assessed after a mean of 33 months.
      RESULTS: At baseline, mean age was 63+/-9 years and mean LVEF was 52+/-12%. In
      61% there was a history of myocardial infarction and 83% had previously been
      revascularised. Mortality was 5.5% at one year and 13.5% at three years. New
      revascularisation options were found in 9.5% of the 243 screened patients at
      baseline coronary angiography. Additionally, in 6% of the trial patients the
      protocol-specified angiogram after three months revealed new significant
      stenosis, which was treated by percutaneous intervention. CONCLUSIONS: Annual
      mortality in refractory angina pectoris seems higher than in stable angina
      pectoris in general, but substantially lower than after myocardial infarction.
      The "refractoriness" of these patients should be re-evaluated regularly, as new
      revascularisation options often occur.

PMID- 18609055
TI  - Repeated image analyses improves accuracy in assessing arterial flow-mediated
      dilatation.
AB  - OBJECTIVES: A high degree of variability has been reported regarding the
      ultrasound-based assessment of flow-mediated dilatation. We wanted to investigate
      the variability and find out how it might be reduced most efficiently. DESIGN:
      Brachial artery flow-mediated dilatation was measured by high-resolution
      ultrasound in 22 healthy adults on two consecutive days. Two observers analysed
      all images twice. The total variance was split into variance components and
      estimated hierarchically using the method of restricted maximum likelihood.
      RESULTS: The relative proportional contributions from intraobserver (residual),
      interobserver, interpatient and interday variance components, with percentage
      dilatation as outcome variable, were 0.41, 0.18, 0.25, and 0.15, respectively.
      CONCLUSIONS: The major source of variability when assessing flow-mediated
      dilatation was found to be intraobserver variability. The simplest way to reduce
      total variability is for the observer to average results from repeated image
      analyses. We suggest that three repetitions are sufficient. This will reduce the
      total variance by 30%.

PMID- 18609056
TI  - Surgical management of ascending aortic aneurysm due to non-infectious aortitis.
AB  - OBJECTIVES: We reviewed the spectrum of disease and early outcomes of patients
      undergoing ascending aortic surgery for Giant cell aortitis (GCA). DESIGN: Of 1
      259 patients undergoing repair of ascending aortic aneurysms between January 1993
      and July 2006, 100 had histologic evidence of GCA or lymphoplasmacytic aortitis.
      RESULTS: Operative Mortality was 4% (4/100). One patient underwent aortoplasty
      and aortic valve replacement (AVR). Among 99 patients undergoing graft
      replacement of the ascending aorta, distal disease required hemiarch replacement
      in 33 and total arch replacement in 14. Proximal aneurismal disease of the root
      was managed by mechanical or biological root replacement (n=18), Yacoub
      remodeling (n=2) or David reimplantation (n=9). Another 12 patients had separate
      AVR and ascending graft, while 26 had AR corrected by restoration of proper
      sinotubular junction diameter. In total, of 63 patients with AR, 38 had a valve
      preserving procedure (61%). CONCLUSIONS: Ascending aortic aneurismal disease due
      to GCA is frequently associated with proximal and/or distal disease. Valve
      sparing procedures are technically feasible for many, although late durability is
      uncertain.

PMID- 18609057
TI  - Aerobic interval training improves VO2 peak in coronary artery disease patients;
      no additional effect from hyperoxia.
AB  - OBJECTIVES: To investigate whether hyperoxic aerobic interval training improves
      training quality in coronary artery disease patients. DESIGN: Twenty-one stable
      coronary artery disease patients were recruited to hyperoxic (n=10) and normoxic
      (n=11) groups (age: 62.4 +/- 6.8 years). Patients underwent 30 supervised 44
      minutes interval training sessions using treadmill walking, at 85-95% of peak
      heart rate. RESULTS: Arterial saturation was significantly increased by 3% at
      pretest from normoxic to hyperoxic testing conditions. Peak oxygen uptake and
      stroke volume increased significantly by 16% and 17% (p<0.05) and by 16% and 18%
      (p<0.05) in the hyperoxic and normoxic training groups respectively. No
      difference was revealed between groups for peak oxygen uptake and stroke volume.
      Blood volumes were unchanged from pre to post training. Peak oxygen uptake
      measured in normoxia and hyperoxia in the hyperoxia training group revealed no
      difference. CONCLUSION: The present study shows that breathing 100% oxygen
      enriched air during aerobic interval training in stable coronary artery disease
      patients does not improve peak oxygen uptake above the level attained with
      normoxic training.

PMID- 18609058
TI  - Carbohydrate restriction as the default treatment for type 2 diabetes and
      metabolic syndrome.
AB  - Dietary carbohydrate restriction in the treatment of diabetes and metabolic
      syndrome is based on an underlying principle of control of insulin secretion and
      the theory that insulin resistance is a response to chronic hyperglycemia and
      hyperinsulinemia. As such, the theory is intuitive and has substantial
      experimental support. It has generally been opposed by health agencies because of
      concern that carbohydrate will be replaced by fat, particularly saturated fat,
      thereby increasing the risk of cardiovascular disease as dictated by the so
      called diet-heart hypothesis. Here we summarize recent data showing that, in
      fact, substitution of fat for carbohydrate generally improves cardiovascular risk
      factors. Removing the barrier of concern about dietary fat makes carbohydrate
      restriction a reasonable, if not the preferred method for treating type 2
      diabetes and metabolic syndrome. We emphasize the ability of low carbohydrate
      diets to improve glycemic control, hemoglobin A1C and to reduce medication. We
      review evidence that such diets are effective even in the absence of weight loss.

PMID- 18609060
TI  - Cholesterol does not cause coronary heart disease in contrast to stress.
AB  - The belief that coronary atherosclerosis is due to high cholesterol from
      increased saturated fat intake originated from experiments in herbivorous
      animals. It was reinforced by reports allegedly demonstrating this sequence of
      events in various populations but ignoring contradictory data. The idea has been
      perpetuated by powerful forces using similar tactics to preserve the profit and
      the reputations of those who promote this doctrine. Opponents find it difficult
      to publish their scientifically supported opinions. The advent of statins has
      further fuelled this fallacious lipid hypothesis, despite compelling evidence
      that their effect is not due to cholesterol lowering and that serious side
      effects have been suppressed and alleged benefits have been hyped. The adverse
      effects of the cholesterol campaign on health, quality of life, the economy and
      medical research are inestimable. It is imperative that public health officials,
      physicians and patients are apprised of proof that it is misguided, malicious and
      malignant.

PMID- 18609061
TI  - Myocardial topical negative pressure increases blood flow in hypothermic,
      ischemic myocardium.
AB  - OBJECTIVES: Hypothermia protects the myocardium from oxidative injury during
      ischemic stress and reperfusion. We have previously shown that topical negative
      pressure (TNP) of -50 mmHg significantly increases microvascular blood flow in
      the underlying myocardium in normal, ischemic, and reperfused porcine myocardium.
      The present study was designed to elucidate the effect of TNP between -50 mmHg
      and -150 mmHg on microvascular blood flow in ischemic myocardium during
      hypothermia. DESIGN: The microvascular blood flow in the myocardium was recorded,
      in seven pigs, using laser Doppler velocimetry. Analyses were performed in the
      epicardium and in the myocardium, after 40 minutes of occlusion of the LAD
      followed by cooling to 31 degrees C. RESULTS: A TNP of -50 mmHg applied to the
      epicardium, from 23.3 +/- 3.8 PU to 104.2 +/- 31.3 PU (*p<0.05), and in the
      myocardium, from 35.0 +/- 7.2 PU to 74.2 +/- 21.8 PU (*p<0.05). CONCLUSIONS: Only
      a TNP level of -50 mmHg significantly increased the microvascular blood flow in
      both the epicardium and in the myocardium during hypothermia.

PMID- 18609062
TI  - Left ventricular diastolic function in patients with treated haemochromatosis.
AB  - OBJECTIVES: We recently demonstrated reduced exercise capacity in phlebotomy
      treated genetic haemochromatosis in spite of normal systolic function. The
      present objective was to investigate diastolic function at rest. DESIGN:
      Diastolic function was echocardiographically assessed in 132 phlebotomy treated
      genetic haemochromatosis patients and 50 controls. RESULTS: Patients had higher
      body mass index and heart rate, higher transmitral early (E) (11.2+/-2.6 versus
      10.4+/-2.2 cm) and atrial (A) (5.7+/-1.6 versus 5.0+/-1.6) velocity time
      integrals, pulmonary venous systolic peak velocity (0.58+/-0.12 versus 0.54+/
      0.13 m/s) and ratio of E to spectral tissue Doppler E' velocity (6.3+/-1.6 versus
      5.6+/-1.4, all p <0.05). Independently of age, heart rate, systolic blood
      pressure and body weight, having haemochromatosis remained statistically
      significantly associated with higher E (beta=0.27) and A (beta =0.18) velocity
      time integrals, pulmonary venous systolic peak velocity (beta =0.21), and E/E'
      ratio (beta=0.25) in separate multivariate analyses (all p <0.05). In the
      youngest age tertile, patients had longer isovolumic relaxation time and lower E'
      than controls. CONCLUSION: Our findings are compatible with mildly impaired
      diastolic function in treated haemochromatosis, with delayed relaxation in the
      younger tertile, and an elevated filling pressure and pseudonormalisation with
      increasing age.

PMID- 18609063
TI  - Women and statin use: a women's health advocacy perspective.
AB  - This paper is based on a longer report on the benefits, safety and modalities of
      information representation with regard to women and statin use, situated within
      the historical context of Women's Health Movement which has advocated for
      unbiased, appropriate medical research and prescribing for women based on the
      goals of full-disclosure, informed consent, evidence-based medicine and gender
      based analysis. The evidence base for prescribing statins for women, especially
      for primary prevention is weak, yet Canadian data suggest that half of all
      prescriptions are for women. Safety meta-analyses do not disaggregate for women;
      do not consider female vulnerability to statin induced muscle problems, and women
      centred concerns such as breast-cancer, miscarriage or birth defects are under
      researched. Many trials have not published their non-cardiac serious adverse
      event data. These factors suggest that the standards of full-disclosure, informed
      consent, evidence-based prescribing and gender-based analysis are not being met
      and women should proceed with caution.

PMID- 18609064
TI  - Postoperative delirium and health related quality of life after coronary artery
      bypass grafting.
AB  - OBJECTIVES: We wanted to identify determinants for postoperative delirium and its
      influence on health related quality of life (HRQoL) during 36-month follow-up of
      coronary artery bypass (CABG) patients. DESIGN: A total of 302 patients were
      retrospectively analyzed. HRQoL was assessed prospectively by the 15D instrument.
      Delirium was diagnosed clinically. RESULTS: The incidence of delirium was 6.0%.
      The cumulative survival (all-cause death) in 36 months was 96.1% in patients
      without delirium and 77.8% in patients with delirium. Age, cerebral disease,
      chronic heart failure, male gender, postoperative pneumonia and low output
      syndrome were predictors for delirium. Delirium patients needed more resources
      i.e. intensive care or total duration of hospitalization and experienced no
      positive change in HRQoL. Moreover patients with high preoperative 15D score
      tended to suffer fairly severe but reversible impairment during the first 6
      months after the operation. CONCLUSIONS: Preoperatively older and sicker patients
      with complicated postoperative course are at higher risk of developing delirium
      after CABG. Preoperative status and operative complications together with
      delirium may exert negative influence on forthcoming HRQoL, which is seen
      especially in patients with a relatively high preoperative level of HRQoL.

PMID- 18609065
TI  - The anti-inflammatory effect of bradykinin preconditioning in coronary artery
      bypass grafting (bradykinin and preconditioning).
AB  - OBJECTIVE: The present study was designed to investigate the cardioprotective
      effect of exogenous administration of bradykinin (BK) in cardiac surgery.
      METHODS: Forty-one patients who were scheduled for isolated coronary artery
      bypass grafting (CABG) were randomized into Control group and BK group. BK
      patients received 25 microg bradykinin infusion for 7 minutes before the
      cardiopulmonary bypass (CPB). Release of cardiac specific troponin I (TnI) and
      creatine kinase cardiac isoenzyme (CK-MB) was recorded. Perioperative circulating
      cytokine interleukin (IL)-6, 8 and 10 were measured. RESULTS: There was no
      significant difference in TnI between groups. However, BK patients released
      significantly less CK-MB than the controls (p =0.043). Systemic plasma levels of
      IL-6, IL-8 and IL-10 increased significantly after reperfusion in both groups as
      compared with baseline (p <0.05). The ratio of IL-8 to IL-10 was significantly
      lower in BK groups than in controls (p =0.03). CONCLUSIONS: We conclude that
      exogenous administration of BK prior to CPB in CABG patients attenuates ischemic
      myocardial injury. It also shifts the circulating inflammatory cytokine balance
      towards the anti-inflammatory direction.

PMID- 18609066
TI  - Genesis of hepatic fibrosis and its biochemical markers.
AB  - Liver fibrosis is characterized by an abnormal hepatic accumulation of
      extracellular matrix (ECM) that results from both increased deposition and
      reduced degradation of collagen fibres. Fibrotic liver injury results in
      activation of the hepatic stellate cell (HSC). Surrogate markers are gradually
      being substituted for biomarkers that reflect the complex balance between
      synthesis and degradation of the extracellular matrix. Once the hepatic stellate
      cell is activated, the preceding matrix changes and recurrent injurious stimuli
      will perpetuate the activated state. The ECM directs cellular differentiation,
      migration, proliferation and fibrogenic activation or deactivation. The
      metabolism of the extracellular matrix is closely regulated by matrix
      metalloproteinases (MMP) and their specific tissue inhibitors (TIMP). Although
      liver biopsy combined with connective tissue stains has been a mainstay of
      diagnosis, there is a need for less invasive methods. These diagnostic markers
      should be considered in combination with liver function tests, ultrasonography
      and clinical manifestations.

PMID- 18609067
TI  - Evaluation of blood oxidative stress-related parameters in alcoholic liver
      disease and non-alcoholic fatty liver disease.
AB  - Oxidative stress is implicated in the pathogenesis of liver disease. We
      investigated oxidative stress-related parameters and correlated with clinical
      findings in 35 non-alcoholic fatty liver disease (NAFLD) patients, 38 alcoholic
      liver disease (ALD) patients and 38 normal subjects. NAFLD patients showed
      significantly higher body mass index, cholesterol, LDL-cholesterol, VLDL
      cholesterol levels and transaminase activities compared to the other two groups.
      Haematological parameters were significantly altered in ALD patients and were
      reported only in male subjects. Glutathione content, catalase activity,
      glutathione reductase activity and glutathione peroxidase activity in NAFLD
      patients were reduced by 10.7 %, 18.5 %, 8.1 % and 16.8 %, respectively, and in
      ALD patients by 21.8 %, 29.6 %, 24.3 % and 45.3 %, respectively, compared to the
      normal group. However, thiobarbituric acid reactive substance content, superoxide
      dismutase activity and glutathione s-transferase activity were increased by 35.2
      %, 31.6 % and 5.4 %, respectively, in NAFLD patients, and in ALD patients by 75.2
      %, 72.7 % and 32.4 %, respectively, compared to the normal group. Oxidative
      stress is associated with collagen production and leads to fibrosis. Type IV
      collagen level in NAFLD patients (190.6 +/- 83 ng/mL) was significantly higher
      than in the normal group (124.5 +/- 14.5 ng/mL) and lower than in ALD patients
      (373.4 +/- 170 ng/mL). While type IV collagen level of >124 ng/mL was a predictor
      of NAFLD patients from normal subjects, elevated ALT (>40 IU/L) activity could
      discriminate either of the liver disease patients from normal subjects.

PMID- 18609073
TI  - IMP dehydrogenase basal activity in MOLT-4 human leukaemia cells is altered by
      mycophenolic acid and 6-thioguanosine.
AB  - OBJECTIVE: Depletion of guanine and deoxyguanine nucleotides by inhibition of
      inosine 5'-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205) or introduction of 6
      thioguanine nucleotide antimetabolites are two principles of retarding cell
      proliferation by interference with the cellular purine nucleotide pool. IMPDH
      activity may be a promising pharmacodynamic biomarker during immunosuppressive
      and anticancer pharmacotherapy. The aim of the study was to investigate the
      impact of mycophenolic acid (MPA) and 6-thioguanosine (tGuO) on IMPDH basal
      activity. MATERIAL AND METHODS: We studied the IMPDH basal activity (i.e. the
      enzyme activity following inhibitor exposure, but measured in absence of the
      inhibitor) in response to increasing concentrations of the IMPDH inhibitor MPA
      and the antimetabolite tGuO in MOLT-4 human leukaemia cells. In parallel, IMPDH
      gene expression and cellular purine nucleotide concentrations were examined.
      RESULTS: A biphasic concentration-dependent influence of MPA on the IMPDH basal
      activity was observed. At concentrations < or =IC50, MPA increased the IMPDH
      basal activity. The increase was associated with elevated expression of IMPDH2.
      Despite increased expression, the basal enzyme activity decreased following
      exposure to high MPA concentrations. The IMPDH2 expression increased modestly in
      response to tGuO exposure. However, the IMPDH basal activity decreased when the
      cells were exposed to a proliferation-blocking tGuO concentration. CONCLUSIONS:
      These findings demonstrate that IMPDH basal activity is influenced by MPA and
      tGuO, and suggest that reduced IMPDH basal activity is related to the
      proliferation-blocking effects of these agents.

PMID- 18609074
TI  - Reference data for distal blood pressure in healthy elderly and middle-aged
      individuals measured with the strain gauge technique. Part II: Distal blood
      pressure after exercise.
AB  - OBJECTIVE: Distal blood pressure (DBP) determination after an exercise test is
      used on suspicion of arterial peripheral vascular disease (apvd). In our
      department. the average age of these patients is about 60 years. The usual
      reference values for pressures after exercise were based on data collected in the
      early 1970s from healthy individuals in the age range 21-26 years. Our aims were
      to collect new reference data for DBP at ankle level after exercise based on
      older populations, and to compare between reference data for different age groups
      to find out whether the normal values are dependent on age. MATERIAL AND METHODS:
      DBP after exercise was measured using the strain-gauge technique on individuals
      in two groups: group I comprising 25 healthy persons aged between 61 and 82
      years, and group II 14 healthy persons aged between 45 and 58 years. Strict rules
      of inclusion were followed. RESULTS: Normal values are dependent on age. The
      average differences (ankle DBP(after)-ankle DBP(before)) immediately after
      walking were 25 mmHg, 12 mmHg and -8 mmHg in group I, group II and the old data,
      respectively. Comparison among groups showed significant differences (p< or
      =0.01). CONCLUSION: Normal values for elderly and middle-aged persons are
      presented. Use of normal values based on young people may result in
      underestimation of DBP response and hence underestimation of the degree of
      possible apvd, especially in elderly individuals.

PMID- 18609079
TI  - ALIS-FLP: amplified ligation selected fragment-length polymorphism method for
      microbial genotyping.
AB  - A DNA fingerprinting method known as ALIS-FLP (amplified ligation selected
      fragment-length polymorphism) has been developed for selective and specific
      amplification of restriction fragments from TspRI restriction endonuclease
      digested genomic DNA. The method is similar to AFLP, but differs in that only one
      specific restriction enzyme (TspRI) is used. The cohesive ends of the DNA
      fragments are ligated with two types of oligonucleotide. A long oligonucleotide
      containing the primer site and the specific 9 nt 3 prime end, which is
      complementary to specific 9 nt, cohesive 3 prime end of the TspRI genomic DNA
      fragment, and a short, degenerated, oligonucleotide covering the remaining TspRI
      cohesive ends. Other cohesive ends are covered by a short degenerated
      oligonucleotide lacking the primer site. The ligation mixture is used as a
      template for amplification using a single primer corresponding to the 5 prime end
      of the long, specific oligonucleotide. The selection of TspRI digested genomic
      DNA fragments for amplification is achieved by sequence selective ligation of the
      specific long oligonucleotide carrying the primer site to both ends of the
      specific target fragment. This technique allows for differentiation of the
      organisms without previous knowledge of their DNA sequence. The usefulness of the
      method is confirmed by genotyping of 70 previously characterized clinical E. coli
      isolates. The grouping obtained was identical to the results of REA-PFGE.
      Versatility of the method is highlighted, i.e. its combining the advantages of
      the AFLP technique with a simple, rapid and cheap polymerase chain reaction
      product detection method.

PMID- 18609080
TI  - Endothelial dysfunction and inflammation predict development of diabetic
      nephropathy in the Irbesartan in Patients with Type 2 Diabetes and
      Microalbuminuria (IRMA 2) study.
AB  - OBJECTIVE: To evaluate risk factors for progression from persistent
      microalbuminuria to diabetic nephropathy in the Irbesartan in Patients with Type
      2 diabetes and Microalbuminuria (IRMA 2) study, including biomarkers of
      endothelial dysfunction, chronic low-grade inflammation, growth factors and
      advanced glycation end products (AGE peptides). METHODS: IRMA 2 was a 2-year
      multicentre, randomized, double-blind trial comparing irbesartan (150 and 300 mg
      once daily) versus placebo. The primary end-point was time to onset of diabetic
      nephropathy. Samples from a subgroup from the placebo and the 300 mg irbesartan
      treatment group were used in this post-hoc analysis (n = 269, 68 %). Nine
      biomarkers were analysed: high sensitivity C-reactive protein (hs-CRP),
      interleukin 6 (IL-6), fibrinogen, von Willebrand Factor (vWf), soluble vascular
      cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule
      1 (sICAM-1), sE-selectin, transforming growth factor-beta (TGF-beta) and AGE
      peptides. Mean standard deviation scores (Z-scores) were used to combine
      biomarker information. RESULTS: In a Cox enter model with combined Z-scores for
      biomarkers of endothelial dysfunction (vWf, sVCAM-1, sICAM-1, sE-selectin) and
      for biomarkers of inflammation (hs-CRP, IL-6, fibrinogen), endothelial
      dysfunction (hazard ratio for a 28 % increase ( = 1 SD) in Z-score) 3.20 (1.56 to
      6.56), p = 0.001) and UAER (HR for a 75 % increase ( = 1 SD) in UAER) 2.61 (1.30
      to 5.23), p = 0.007) were found as independent predictors. Independently, IL-6
      and vWf predicted the end-point. In addition, endothelial Z-score was associated
      with progression of albuminuria (p = 0.038). CONCLUSION: Endothelial dysfunction
      and possibly inflammation are novel predictors of progression to diabetic
      nephropathy in patients with type 2 diabetes and microalbuminuria independently
      of traditional risk factors. ClinicalTrials.gov ID: NCT00317915.

PMID- 18609082
TI  - Association between markers of renal function and C-reactive protein level in the
      elderly: confounding by functional status.
AB  - OBJECTIVE: To analyse the cross-sectional association between measures of renal
      function and inflammation in an elderly population and to evaluate the
      confounding effect of impaired physical functioning on these relationships.
      MATERIAL AND METHODS: Cystatin C and creatinine were measured in serum samples
      from 1110 elderly subjects in a community-based cross-sectional survey (Lieto
      Study) in southwestern Finland. Glomerular filtration rate (GFR) was estimated by
      means of the Modification of Diet in Renal Disease (MDRD) equation. Associations
      between renal measures and sensitive C-reactive protein (CRP) and the impact of
      functional status were determined by multivariate linear models. RESULTS: Based
      on standardized coefficients, cystatin C (beta 0.19; p<0.001) showed the
      strongest association with CRP compared to creatinine (beta 0.14; p<0.001) and
      estimated GFR (beta -0.13; p<0.001). Levels of CRP linearly increased across
      quintiles of cystatin C, whereas for creatinine and estimated GFR the increase
      was less graded. Impaired physical functioning was strongly associated with
      elevated levels of cystatin C (p<0.001) and CRP (p<0.001), but not with
      creatinine (p = 0.45) or estimated GFR (p = 0.38). For persons with impaired
      physical functioning, the odds ratio for belonging to the highest compared to the
      lowest cystatin C quintile was 7.04 (95% confidence interval 3.49-14.9; p<0.001),
      whereas for creatinine and estimated GFR this difference was not significant.
      CONCLUSION: The weaker association observed between CRP and creatinine-based
      measures, as compared to cystatin C, reflects the misclassification of elderly
      frail subjects as having normal kidney function rather than suggests cystatin C
      itself to be a marker of inflammation.

PMID- 18609085
TI  - Advanced statistics and data analysis in laboratory medicine: steep learning
      curve but substantial rewards.

PMID- 18609087
TI  - Prognostic significance of hepatocyte growth factor and microvessel bone marrow
      density in patients with chronic myeloid leukaemia.
AB  - OBJECTIVE: The aims of the study were: (1) to perform a complex angiogenic
      assessment in chronic myeloid leukaemia (CML) patients using multiple parameters:
      bone marrow microvessel density (MVD), bone marrow immunohistochemical cellular
      expressions of vascular endothelial growth factor (VEGF) and its receptor KDR, as
      well as hepatocyte growth factor (HGF) and its receptor MET, and the plasma VEGF
      and HGF; and (2) to determine the clinical significance of these factors for
      patients with CML. MATERIAL AND METHODS: The VEGF and HGF plasma levels were
      analysed by ELISA in 38 newly diagnosed CML patients. Immunohistochemical methods
      were used to visualize the MVD as well as the cellular VEGF/KDR and HGF/MET
      expression. RESULTS: We found an increased MVD, cellular VEGF/KDR and HGF/MET
      expression and elevated plasma VEGF and HGF in CML patients. The plasma HGF,
      cellular HGF and MET expression correlated with the CML phase. The plasma HGF
      correlated with all markers reflecting the tumour burden (leucocytes, blast
      percentage, splenomegaly and LDH) as well as with the phase of CML and overall
      survival of the patients. Cox regression analysis determined the prognostic
      relevance of HGF and MVD parameters, but not for the plasma VEGF and cellular
      VEGF and KDR. CONCLUSIONS: Using a complex angiogenic assessment we determined an
      increased angiogenesis in CML patients. No prognostic relevance was found for
      VEGF plasma levels or VEGF/KDR cellular bone marrow expression. The increased
      cellular HGF and MET expressions could be considered high-risk factors for these
      patients. Plasma HGF and MVD were shown to be independent prognostic parameters
      for patients' survival.

PMID- 18609088
TI  - Difficulties for primary health care staff in interpreting bacterial findings on
      a device for simplified urinary culture.
AB  - The reliability of interpretations of findings from dip-slide devices for
      culturing urine was investigated in a national Swedish external quality
      assessment (EQA) programme. Also investigated was the extent of improvement in
      the examination procedure achieved through personnel training programmes and
      information. According to Swedish national recommendations, dip-slide should only
      be used in primary health care (PHC) in cases of uncomplicated urinary tract
      infection (UTI) in females of childbearing age. The recommendations also define
      six possible outcomes of a dip-slide examination, outcomes that have formed the
      basis for the EQA programme since 2001. No improvement in ability to classify
      readings correctly into the six categories was noted for the period 2001 to 2006.
      Preparations containing 'mixed flora' presented participants with the greatest
      difficulty, with only 28 % correct reports. The EQA programme, with educational
      components and voluntary participation, has not improved quality. The
      disappointing results might be a reflection of the limited effort and resources
      allocated by clinical microbiology laboratories for training and for sustaining
      proficiency in the evaluation of dip-slides. For these reasons, we cannot at
      present recommend the dip-slide technique for use in PHC settings.

PMID- 18609089
TI  - Identifying sources and estimating glandular output of salivary TIMP-1.
AB  - OBJECTIVE: Tissue inhibitor of metalloproteinases 1 (TIMP-1) has been identified
      as a potential biomarker in diseases such as cancer, cardiovascular diseases and
      diabetes. Since TIMP-1 resides in most tissues and bodily fluids, we evaluated
      the potential of using saliva to obtain reproducible TIMP-1 measurements in a non
      invasive manner. MATERIAL AND METHODS: Samples of unstimulated and stimulated
      whole saliva and saliva collected from individual glands were analysed for TIMP-1
      content. A TIMP-1 ELISA was validated for use in saliva testing and the most
      optimal sampling and handling procedures for reproducible measurements
      identified. Western blotting and MALDI-TOF mass spectrometry were used for
      confirmatory analyses. RESULTS: The TIMP-1 ELISA was found suitable for saliva
      measurements. All saliva secretions contained TIMP-1, but in different
      concentrations ranging from 2.81 ng/mL in submandibular/sublingual saliva to
      173.88 ng/mL in parotid saliva. TIMP-1 concentrations were influenced to a
      varying degree by fluctuations in flow. We found the lowest output in
      submandibular/sublingual saliva stimulated with 0.5% citric acid (3.56 ng/min)
      and highest output in chewing-stimulated whole saliva (267.01 ng/min).
      CONCLUSION: This study shows that saliva contains authentic TIMP-1, the
      concentration of which was found to depend on gland type and salivary flow.
      Stimulated whole saliva is suggested as a reliable and easily accessible source
      for TIMP-1 determinations in bodily fluids.

PMID- 18609092
TI  - Autonomic dysfunction in cirrhosis and portal hypertension.
AB  - Liver cirrhosis and portal hypertension are frequently associated with signs of
      circulatory dysfunction and peripheral polyneuropathy, which includes defects of
      the autonomic nervous system. Autonomic dysfunction, which is seen in both
      alcoholic and non-alcoholic liver cirrhosis and increases with severity and
      duration of the liver disease, is associated with a significant increase in
      mortality. The lack of total resolution after liver transplantation indicates
      that the autonomic neuropathy is not exclusively functional. This article
      highlights some aspects of the autonomic dysfunction in chronic liver disease. A
      description is given of its aetiology and the typical circulatory dysfunction
      with characteristic hyperdynamic and hyporeactive circulation and heart failure,
      and the most important tests of the autonomic nervous system.

PMID- 18609093
TI  - Sources of biological and methodological variation in salivary cortisol and their
      impact on measurement among healthy adults: a review.
AB  - Salivary cortisol is often used in occupational field studies when measuring
      stress reactions. For purposes of precision and accuracy in measurement, and
      interpretation of results, it is crucial to know the sources of variability that
      exert systematic influence on sampling. Variability can be both biological and
      methodological in origin, and failure to identify its sources may induce
      erroneous interpretations of Type I and Type II. This review aims to increase our
      knowledge and provide an overview of the biological and methodological variations
      of relevance for field measurements of salivary cortisol. It is concluded that:
      (i) time of sampling has to be carefully registered and included in the
      statistical analysis; (ii) samples have to be collected at the same time of year
      in longitudinal designs; (iii) food intake has to be avoided in at least the 2 h
      before sampling; (iv) vigorous exercise has to be avoided in at least the 2 h,
      preferably longer, before saliva is collected for measurement of cortisol; (v)
      variation in results obtained by different laboratory techniques emphasizes use
      of the same, or otherwise made comparable, laboratory techniques; (vi)
      concentration of cortisol is dependent on the material of the tampon; (vii)
      despite the absence of hard evidence, it is recommended that information be
      collected and results possibly statistically controlled for alcohol consumption,
      medication, such as oral contraceptives, and treatment for mental diseases;
      (viii) saliva samples can be stored at -20 degrees C for at least 1 year; (ix)
      cross-comparisons of absolute concentrations across studies might be difficult
      and therefore the establishment of reference intervals for the population studied
      and method used is recommended.

PMID- 18609095
TI  - Liposome-mediated transfection with extract from neonatal rat cardiomyocytes
      induces transdifferentiation of human adipose-derived stem cells into
      cardiomyocytes.
AB  - OBJECTIVE: Recent studies indicate that direct cell-to-cell interaction is
      involved in transdifferentiation of adult stem cells into cardiomyocytes. We
      investigated whether transdifferentiation of human adipose-tissue-derived stem
      cells could be achieved by transfecting the cells with a nuclear neonatal
      cardiomyocyte extract using a liposome-based transfection system. MATERIAL AND
      METHODS: In this study, we isolated stem cells derived from human subcutaneous
      adipose tissue. These cells were transfected with nuclear protein extracts from
      either isolated cardiomyocytes or whole hearts of neonatal rats. Results. We
      found that transfection induced expression of the cardiac markers alpha
      sarcomeric actin, Nkx2.5, troponin I and troponin T after 1-3 weeks. Whole-heart
      protein extracts showed the additional capacity to induce differentiation into
      endothelial-like and smooth muscle-like cells. CONCLUSION: We demonstrate that
      transfection with nuclear protein extracts from neonatal rat cardiomyocytes can
      induce a cardiomyogenic differentiation pathway in human stem cells.

PMID- 18609099
TI  - Urinary osteocalcin and other markers of bone metabolism: the effect of
      risedronate therapy.
AB  - OBJECTIVE: Serum osteocalcin (S-OC) is widely used as an index of bone formation.
      However, there is evidence that some urinary fragments of OC reflect resorption
      and might be useful in monitoring antiresorptive therapy. Here, we report 6-month
      changes in urinary midfragments of osteocalcin (U-MidOC) and other bone turnover
      markers in response to risedronate treatment. MATERIAL AND METHODS: The study
      group comprised 19 patients with postmenopausal osteoporosis, aged 49-66 years,
      and receiving risedronate therapy. Fifty-four premenopausal women served as
      controls. Osteoporosis was diagnosed by lumbal bone mineral density (BMD).
      Urinary osteocalcin was measured by the U-MidOC assay for midfragments. Bone
      formation was assessed by S-PINP and S-OC, and resorption by S-CTx-I. RESULTS: At
      baseline, U-MidOC was significantly correlated only with S-OC. After the 1st
      month of therapy, a similar decrease was observed in the values of U-MidOC and S
      CTx-I, but in formation markers S-P1NP and S-OC only after three months. The
      rapid decrease in U-MidOC, analogous to S-CTX-I, and the different kinetics for
      urinary and serum OC suggest that urinary OC midfragments are more associated
      with resorption than S-OC. An association was also observed between the 1-month
      change in U-MidOC and 12-month gain in lumbar BMD. The response in U-MidOC after
      only the 1st month of therapy makes it a potential marker for monitoring the
      effect of risedronate, presumably reflecting different aspects of bone resorption
      than S-CTx-I does.

PMID- 18609101
TI  - Chitotriosidase and soluble IL-2 receptor: comparison of two markers of
      sarcoidosis severity.
AB  - BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease with an
      unpredictable clinical course characterized by accumulation of activated
      proliferating T lymphocytes and mononuclear phagocytes in affected organs. AIMS
      AND METHODS: The aims of this study were to describe the clinical, radiological
      and immunological features of a population of sarcoidosis patients followed at
      the Sarcoidosis Regional Centre in Siena and to analyse chitotriosidase and sIL
      2R concentrations in serum of these patients in order to understand their
      potential as disease markers. RESULTS: Chitotriosidase and sIL-2R concentrations
      in serum of sarcoidosis patients were found to be significantly higher than in
      healthy controls (p<0.01) and a positive correlation between the two markers was
      documented for the first time. Moreover, chitotriosidase and sIL-2R were
      expressed differently in different radiographic stages of the disease.
      CONCLUSION: Chitotriosidase and sIL-2R are two markers of sarcoidosis of
      different origin, the values of which show a correlation in these patients; they
      are easily detectable in serum and could be useful clinical markers of
      progression.

PMID- 18609102
TI  - Diagnostic performance of plasma high sensitive C-reactive protein in detecting
      three-vessel coronary artery disease: modification by apolipoprotein E genotype.
AB  - OBJECTIVES: Plasma high sensitive C-reactive protein (hsCRP) concentration is an
      important clinical test of systemic inflammation and, like apoE epsilon4 allele,
      an important risk factor of coronary artery disease (CAD). We investigated
      whether the diagnostic performance of plasma hsCRP in detecting severe 3-vessel
      CAD may be modified by apoE epsilon4 carrier status. METHODS: The study
      population (Angiography and Genes Study) comprised 485 Finnish subjects (336 men
      and 149 women, mean age 64.0+/-1.0) undergoing coronary angiography. ApoE
      genotypes were determined by the PCR-based method and by hsCRP using an automatic
      analyser. RESULTS: The diagnostic performance of hsCRP concentration in
      distinguishing 3-vessel CAD from its less widespread forms (non-3-vessel CAD) was
      assessed by receiver operating characteristic curve (ROC) analysis separately in
      apoE epsilon4 non-carriers and epsilon4 carriers. ROC analysis showed that hsCRP
      predicted 3-vessel CAD in apoE epsilon4 non-carriers (AUC 0.646; SE 0.035; p =
      0.0001; 95 % CI 0.578-0.714) but not in epsilon4 carriers (AUC 0.518; SE 0.049; p
      = 0.719; 95 % CI 0.422-0.615). Multinomial logistic regression analysis revealed
      a significant (p<0.05) apoE epsilon4 group versus hsCRP group (<1.0 mg/L/>or=1.0
      mg/L) interaction in relation to incidence of 3-vessel CAD. In apoE epsilon4 non
      carriers, high hsCRP (>or=1.0 mg/L) was significantly (OR 2.1; 95 % CI 1.233
      3.562; p = 0.006) associated with high incidence of 3-vessel CAD after adjustment
      for major CAD risk factors. CONCLUSION: The diagnostic performance of hsCRP in
      distinguishing 3-vessel CAD from less extensive forms of coronary atherosclerosis
      is more accurate in a group of subjects without the apoE epsilon4 allele than in
      patients with it.

PMID- 18609103
TI  - Pooling ambulatory saliva cortisol samples over consecutive days - as reliable as
      arithmetic means.
AB  - OBJECTIVE: When cortisol measurements are to be studied in large populations,
      cost-effective analyses are needed. This study aimed at testing whether one
      pooled cortisol value over three consecutive days is as reliable as using the
      arithmetic mean of the samples from the same measure points. MATERIAL AND
      METHODS: Thirty participants aged between 45 and 69 collected saliva in
      salivettes immediately after awakening (t(1)), 30 min after awakening (t(2)) and
      in the evening (t(3)) during 3 consecutive days. A fixed volume from each of the
      samples (t(1), t(2 )and t(3)) was pooled prior to laboratory analysis. Mean
      levels over 3 days for t(1), t(2 )and t(3) were compared to corresponding levels
      of pooled vials. Cortisol levels were analysed using a radio immunoassay.
      RESULTS: All measures tested had high correlations between mean values and pooled
      samples, exemplified with diurnal deviation r(dif t2-t3) = 0.974 (CI
      0.946;0.987), and awakening response r(dif t2-t1) = 0.982 (CI 0.963;0.991). There
      were no statistical differences between the pooled values and the arithmetic
      means. CONCLUSION: Pooling samples gave as reliable results as arithmetic means
      did. Pooling samples prior to laboratory analysis is a cost-effective method for
      measuring general diurnal cortisol variation in field research projects.

PMID- 18609104
TI  - Fibroblast growth factor-19: development, analytical characterization and
      clinical evaluation of a new ELISA test.
AB  - OBJECTIVE: Since fibroblast growth factor 19 (FGF-19) is a potent metabolic
      regulator that influences glucose and lipid homeostasis, our aim was to develop
      an ELISA assay for measuring FGF-19 in human serum and to investigate its
      concentrations in healthy volunteers and patients suffering from metabolic
      syndrome. MATERIAL AND METHODS: A sandwich ELISA method was developed for
      quantitative determination of human FGF-19 in serum samples. Blood pressure,
      waist circumference, FGF-21 serum levels, serum cholesterol, triacylglycerols,
      HDL-cholesterol, LDL-cholesterol, insulin, glucose, adiponectin, uric acid,
      creatinine, hs-CRP and calculated BMI and Quicki insulin sensitivity index were
      measured in 153 healthy volunteers and 66 persons with metabolic syndrome.
      RESULTS: Neither sex nor age influenced FGF-19 serum concentration in the healthy
      volunteers. Probands with metabolic syndrome had 65 % lower FGF-19 serum values
      than the healthy ones (medians 158.6 versus 242.4 ng/L; p<0.01). FGF-19
      correlated with glucose (r = -0.35, p<0.01), HDL (r = 0.24, p = 0.045),
      triacylglycerols (r = -0.19, p = 0.05) and with a number of other risk factors
      for metabolic syndrome (r = -0.28, p = 0.01). When adjusted to the concentrations
      of triacylglycerols, BMI and glucose, and finally to all data pertinent to FGF-19
      (according to correlation analysis), our data indicate that FGF-19 is an
      independent marker of metabolic syndrome. CONCLUSIONS: The present study
      demonstrates the analytical properties of the ELISA FGF-19 assay and its
      usefulness when studying the metabolic syndrome. Serum concentrations of FGF-19
      could be new key predictors of metabolic syndrome and thereby even a new negative
      risk factor of atherosclerosis.

PMID- 18609106
TI  - Role of the fractalkine receptor CX3CR1 polymorphisms V249I and T280M as risk
      factors for early-onset coronary artery disease in patients with no classic risk
      factors.
AB  - OBJECTIVES: CX3CR1 is a monocyte chemokine receptor and adhesion molecule. Two
      CX3CR1 mutations, V249I and T280M, reportedly decrease coronary artery disease
      (CAD) risk independent of established risk factors. An I249 protective effect is
      attributed to reducing CX3CR1 binding to fractalkine, its ligand. MATERIAL AND
      METHODS: We examined the frequencies of V249I and T280M among early-onset CAD
      patients (G1; n = 149; <50 years), late-onset CAD patients (G2; n = 150; >65
      years) and healthy controls (HC; n = 149, 47-93 years) without known CAD risk
      factors. We compared plasma total cholesterol (TC)/high density lipoprotein-C
      (HDL-C) and apolipoprotein B (APOB)/apolipoprotein AI (APOAI) ratios among the
      groups and mutation carriers and non-carriers, and the prevalence of the
      mutations in G1 and G2 patients with multiple coronary vessel disease (MVD) and
      myocardial infarction (MI). RESULTS: G1 patients had non-significantly lower
      frequencies of I249 versus (vs.) G2 or controls (G1; 51 %, G2: 61 %, controls: 58
      %, p = 0.19), with no difference in T280M (p = 0.8). TC/HDL-C and APOB/APOAI
      ratios were significantly higher in G1 patients vs. G2 and controls (p<0.0001)
      independently of either mutation. More G2 patients had MVD than younger ones
      (p<0.0001); however, more G1 patients were homozygous for V249 compared to G2
      patients, who more often had the I249 allele (p<0.02). There was no such
      association with T280M (p = 0.38). Although more G1 patients had MI, this was not
      mutation related. CONCLUSIONS: There were significantly higher lipid ratios in G1
      compared to G2 and HC (G1>G2>HC), but not in mutation prevalence. I249 mutation
      was associated with MVD in older patients, while V249 homozygosity was associated
      with the early-onset CAD. Neither allele affected MI or lipid levels.

PMID- 18609107
TI  - Measurement of salivary cortisol--effects of replacing polyester with cotton and
      switching antibody.
AB  - Stable performance between-runs are essential in longitudinal studies and when
      different studies are being compared. However, changes in analytical kits and
      laboratory material occur and have the potential to threaten analytical
      stability. In the present case, we examined how salivary cortisol measurements in
      our laboratory were affected by: 1) changes in the tampon material and 2) changes
      in the antibody of the analytical kit. In study 1, saliva from healthy subjects
      (n = 19) was split and spiked to Salivette polyester and cotton tampons,
      respectively, and treated as ordinary samples before being analysed for cortisol
      using a Spectria RIA kit for cortisol. In study 2, 68 anonymous saliva samples
      were analysed with the Spectria Cortisol RIA kit both before and after the
      manufacturer changed the antibody. The change from polyester to cotton tampons
      reduced the measured concentration of salivary cortisol by 62 %. A difference of
      12 % between the two runs with different antibodies could not be attributed to
      differences in storage or in thawing and freezing of samples. To conclude, both a
      change in the material of the Salivette used for collecting saliva samples as
      well as a change of antibody in a kit can have a major impact on measurements, as
      illustrated here for concentrations of cortisol in saliva. It is therefore
      recommended always to check that the analysis stays in statistical control in
      one's own laboratory when changes are made, even if the manufacturer reports that
      the changes should have no effects.

PMID- 18609108
TI  - Reference intervals for carcinoembryonic antigen (CEA), CA125, MUC1, Alfa-foeto
      protein (AFP), neuron-specific enolase (NSE) and CA19.9 from the NORIP study.
AB  - OBJECTIVE: Adhering to current IFCC recommendations, we calculated upper 97.5 %
      reference limits for serum tumor markers. MATERIAL AND METHODS: Serum samples
      from 498 healthy individuals from the Nordic reference interval project (NORIP)
      were investigated for carcinoembryonic antigen (CEA), CA125 and MUC1 (episialin,
      CA15.3) using in-house immunofluorometric assays and, for alpha-foetoprotein
      (AFP), a PerkinElmer Life Sciences assay, neuron-specific enolase (NSE) using an
      in-house immunoradiometric assay and CA19.9 using a Beckman Access assay. All
      assays participate in external quality assessment programs. RESULTS: CEA
      concentrations increased with age and smoking. Upper reference limits for non
      smokers were 3.59 microg/L at 50 years and 4.12 microg/L at 70 years. CA125
      concentrations were age-independent and the upper reference limit was 35.8 kU/L.
      MUC1 increased with age and body mass index (BMI). Upper reference limits were
      31.7 kU/L at 40 years and BMI 24, 37.5 kU/L at 70 years and BMI 24, and 33.7 kU/L
      at 40 years and BMI 30. AFP increases with age, and the upper reference limits
      were 3.82 kU/L at 20 years and 8.70 kU/L at 60 years. An upper reference limit
      for NSE was 8.91 microg/L in non-smokers; smokers exhibited significantly lower
      levels. The upper reference limit for individuals expressing CA19.9 was 28.3
      kU/L. CONCLUSIONS: For AFP, CA125 and CA19.9, the reference levels obtained were
      close to previously reported reference ranges. Smoking and age were confirmed as
      covariates for CEA. The associations between MUC1 with age and BMI and between
      NSE and smoking have not been reported previously.

PMID- 18609111
TI  - Acute variation of biochemical markers of muscle damage following a 21-km, half
      marathon run.
AB  - OBJECTIVE: Although there is information on biochemical markers of muscle and
      cardiac damage following strenuous exercise, little is known about the kinetics
      of these markers in athletes performing sub-maximal exercise. MATERIAL AND
      METHODS: Fifteen healthy, trained, Caucasian males took part in a 21-km run.
      Blood samples were collected before the run, immediately after (post), and 3 h, 6
      h and 24 h thereafter. Biochemical markers of muscle and cardiac damage were
      evaluated on the Modular System, employing proprietary reagents. In no case did
      the concentration of troponin T increase by >0.03 ng/mL. The values of aspartate
      aminotransferase (AST), creatine kinase (CK), CK MB, lactate dehydrogenase (LDH)
      and myoglobin increased significantly immediately after the run and remained
      elevated 24 h thereafter. RESULTS: The number of subjects with values above the
      upper limit of the relative reference ranges did not vary throughout the study
      period for AST and LDH, while it increased significantly for CK, CK MB and
      myoglobin. The major variation over the pre-run value was recorded for myoglobin
      (3-fold increment), whereas AST and LDH increased 1.1 and 1.3-fold, respectively.
      CONCLUSIONS: The results suggest the hypothesis that sub-maximal exercise
      influences the concentration of several biomarkers of muscle damage for up to 24
      h with no biochemical signs of myocardial damage.

PMID- 18609113
TI  - Oxidized LDL and anti-oxLDL antibody levels in peripheral atherosclerotic
      disease.
AB  - OBJECTIVE: Oxidative modification of LDL (oxLDL) is important in atherogenesis
      and is proposed as a useful marker for identifying patients with coronary artery
      disease. Antibody to oxLDL (oxLDL Ab) is detected in human sera, although its
      biological significance is not well established. We aimed to measure oxLDL and
      oxLDL Ab in peripheral atherosclerotic disease (PAD) patients, and to examine the
      relation between them in an attempt to understand the role of oxLDL Ab. Total
      risk of atherosclerosis was estimated using the global risk assessment score
      (GRAS) calculated on the basis of age, total cholesterol, HDL cholesterol (HDL
      Chol), diabetes, hypertension and smoking. MATERIAL AND METHODS: Twenty-one
      patients aged 63.05+/-9.13 years, diagnosed by peripheric angiography as PAD, and
      21 healthy controls aged 47.67+/-13.61 years took part in the study. Total LDL
      and HDL cholesterol levels were determined by enzymatic methods. Levels of
      circulating oxLDL were measured by monoclonal antibody 4E6-based competition
      ELISA. IgG class oxLDL Ab titre was measured by ELISA. RESULTS: Compared to
      healthy controls, PAD patients had higher levels of oxLDL (p<0.05), oxLDL Ab
      (p<0.05), LDL cholesterol (LDL-Chol) (p<0.05), total cholesterol (p<0.05) and
      lower HDL-Chol (p<0.05). OxLDL was found to be positively correlated with total
      cholesterol (r = 0.471, p<0.05) and LDL-Chol (r = 0.614, p<0.01) and GRAS (r =
      0.435, p<0.05) and negatively with HDL-Chol (r = -0.459, p<0.05), but not with
      oxLDL Ab in PAD patients. CONCLUSIONS: These findings might indicate that high
      LDL-Chol levels influence the oxidation of LDL and that oxLDL is a possible
      marker of PAD. However, the role of oxLDL Ab in atherosclerosis remains
      controversial.

PMID- 18609114
TI  - Lack of association of coeliac disease with idiopathic and ischaemic dilated
      cardiomyopathies.
AB  - OBJECTIVE: A prevalence of coeliac disease higher than in the general population
      has been reported not only in patients with idiopathic dilated cardiomyopathy, a
      presumable autoimmune disease, but also in patients with ischaemic or valvular
      cardiomyopathy. The evidence is controversial, however, and the concept itself of
      an association unrelated to aetiology is intriguing and warrants further testing.
      The aim of our study was to assess the prevalence of coeliac disease in a cohort
      of patients with dilated cardiomyopathy screened for the presence of serum anti
      transglutaminase antibodies. We provisionally assessed the sensitivity and
      specificity of two commercially available kits for tissue transglutaminase
      antibodies detection. MATERIAL AND METHODS: We screened for anti-transglutaminase
      antibodies in 350 consecutive patients with idiopathic (n = 182) and with
      ischaemic (n = 168) dilated cardiomyopathy using the previously validated method
      for anti-transglutaminase antibody assay. Coeliac disease diagnosis has been
      confirmed by duodenal histopathology in patients testing positive at serological
      screening. RESULTS: Two coeliac patients (0.6% prevalence) have been identified,
      one with idiopathic and one with ischaemic dilated cardiomyopathy. They presented
      with iron deficiency anaemia and with recurrent abdominal pain and diarrhoea,
      respectively, and both had villous atrophy at histopathology. After 1 year on a
      gluten-free diet, the echocardiographic parameters did not improve in either
      patient. CONCLUSIONS: Our results indicate that the prevalence of coeliac disease
      in patients with dilated cardiomyopathies is similar to that reported for the
      Italian general population. The confounding factor of conditions associated with
      both coeliac disease and dilated cardiomyopathies may explain the association
      unrelated to aetiology reported in previous studies mostly based on small sample
      size.

PMID- 18609117
TI  - Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) as a biological
      candidate marker of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by the progressive formation of
      insoluble amyloid plaques and vascular deposits consisting of the amyloid beta
      peptide (Abeta) in the brain. Pathological mechanisms are already active early in
      the presymptomatic stage of AD. BACE1, beta-secretase, is one of the two key
      enzymes in amyloid precursor protein (APP) processing; the other being gamma
      secretase. The Abeta peptide results from cleavage of APP initially by BACE1 to
      produce the C99 fragment and releases soluble APPbeta (sAPPbeta); C99 is then
      further cleaved by gamma-secretase leading to the Abeta peptide. Increased BACE1
      activity and elevated levels of insoluble Abeta peptide have been shown in brain
      tissue of patients with sporadic AD. Since the CSF is in direct contact with the
      extracellular space of the central nervous system, biochemical changes in the
      brain can potentially be reflected in CSF. Therefore, CSF-based detection of
      BACE1 levels and activity might be valuable in aiding early detection and
      prediction, particularly in preclinical or even presymptomatic subjects who are
      at risk of AD. Recently, we were among the first groups to quantitatively analyse
      the enzymatic activities and protein levels of BACE1 in the CSF. Preliminary
      research using recently developed BACE1 ELISAs, BACE1 enzymatic activity,
      sAPPbeta and total Abeta1-x ELISAs were used by examining these hypothesis driven
      functional candidate markers in subjects with clinically diagnosed AD and
      amnestic MCI. Two sandwich ELISAs were used and BACE1 enzymatic activities were
      seen by synthetic fluorescence substrate and total Abeta levels by sandwich
      ELISA. Moreover, elevated CSF levels of BACE1 protein were associated with an
      increased risk ratio in MCI. Interestingly, amnestic MCI subjects showed
      increased levels of BACE1 activity compared to HC and AD patients. For total
      Abeta and tau, increased CSF levels were associated with a higher risk of MCI
      compared to HC as well. BACE1 activity was significantly correlated with BACE1
      protein concentration and total Abeta levels, with Abeta being itself correlated
      with the BACE1 protein level. Currently, independent studies are ongoing to
      validate BACE1 and functionally associated proteins as candidate biomarkers for
      early detection, prediction, progression as well as for biological activity in
      AD.

PMID- 18609119
TI  - Boron detection from blood samples by ICP-AES and ICP-MS during boron neutron
      capture therapy.
AB  - OBJECTIVE: The concept of boron neutron capture therapy (BNCT) involves infusion
      of a (10)B containing tracer into the patient's bloodstream followed by local
      neutron irradiation(s). Accurate estimation of the blood boron level for the
      treatment field before irradiation is required. Boron concentration can be
      quantified by inductively coupled plasma atomic emission spectrometry (ICP-AES),
      mass spectrometry (ICP-MS), spectrofluorometric and direct current atomic
      emission spectrometry (DCP-AES) or by prompt gamma photon detection methods.
      MATERIAL AND METHODS: The blood boron concentrations were analysed and compared
      using ICP-AES and ICP-MS to ensure congruency of the results if the analysis had
      to be changed during the treatment, e.g. for technical reasons. The effect of wet
      ashing on the results was studied in addition. RESULTS: The mean of all samples
      analysed with ICP-MS was 5.8 % lower than with ICP-AES coupled to wet-ashing (R
      (2) = 0.88). Without wet-ashing, the mean of all samples analysed with ICP-MS was
      9.1 % higher than with ICP-AES (R (2) = 0.99). CONCLUSIONS: Boron concentration
      analysed from whole blood samples with ICP-AES correlated well with the values of
      ICP-MS with wet-ashing of the sample matrix, which is generally considered the
      reference method. When using these methods in parallel at certain intervals
      during the treatments, reliability of the blood boron concentration values
      remains satisfactory, taking into account the required accuracy of dose
      determination in the irradiation of cancer patients.

PMID- 18609120
TI  - Different elimination patterns of beta-trace protein, beta2-microglobulin and
      cystatin C in haemodialysis, haemodiafiltration and haemofiltration.
AB  - OBJECTIVE: Low molecular mass proteins (LMMP) are putative uraemic toxins, but
      their elimination is negligible in standard haemodialysis (HD). In this study, we
      used beta(2)-microglobulin, cystatin C and beta-trace protein, which differ in
      molecular mass and charge, to characterize the elimination patterns of three
      different dialysis modalities. MATERIAL AND METHODS: Plasma samples were obtained
      at the start, 30 min after the start, at the end of the dialysis treatment and 30
      min after termination of the dialysis session. Seventeen patients were treated
      with low-flux HD, 13 with post-dilution haemodiafiltration (HDF) and 8 with pre
      dilution haemofiltration (HF). The changes in concentrations of the three LMMPs
      were monitored and expressed as percentages of the concentrations at the start of
      treatments. RESULTS: Conventional HD with low-flux membranes showed a high
      elimination of small molecules (urea and creatinine), but did not reduce the
      levels of the three LMMPs studied. During HDF and HF, there was a significant
      decrease in the plasma levels of cystatin C (to 28 % and 44 %, respectively)
      (p<0.001) and of beta(2)-microglobulin (to 23 % and 33 %, respectively)
      (p<0.001). However, the level of beta-trace protein was significantly reduced (to
      65 %) only after HDF. CONCLUSIONS: The three dialysis modalities showed
      significantly different elimination patterns for the LMMPs studied. Elimination
      of beta-trace protein was lower than those of cystatin C and beta(2)
      microglobulin both in HDF and HF. beta-trace protein was only moderately
      eliminated by HDF and not at all by HF, and may be a useful marker in the
      evaluation of different convective therapies.

PMID- 18609122
TI  - Effects of the H2-receptor antagonist ranitidine on gastric motor function after
      a liquid meal in healthy humans.
AB  - OBJECTIVE: Studies on animals have shown that histamine may be involved in the
      regulation of gastrointestinal smooth muscle tone. However, the role of histamine
      in the regulation of human gastric motor function is not clear. This study
      examined the effect of ranitidine, an H(2)-receptor antagonist, on gastric volume
      and gastric emptying after a liquid meal in healthy humans. MATERIAL AND METHODS:
      Twelve healthy volunteers participated in a randomized crossover study with 50 mg
      ranitidine as a bolus intravenously versus no medication. Gastric volume at
      baseline was determined with single photon emission computed tomography (SPECT)
      after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL
      liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual
      isotope technique with SPECT and planar imaging assessed gastric volume as well
      as gastric emptying. RESULTS: Ranitidine did not change gastric volume before the
      meal, nor at 0 h or 1 h after it. Furthermore, ranitidine did not influence
      gastric retention of meal components after 0.5 h and 1 h. CONCLUSIONS:
      Intravenous bolus injection of 50 mg ranitidine does not modify gastric volume or
      gastric emptying after a 600 mL liquid meal in healthy humans.

PMID- 18609125
TI  - Shared susceptibility for celiac disease and inflammatory bowel disease?

PMID- 18609126
TI  - GG genotype of cyclin D1 G870A polymorphism is associated with non-cardiac
      gastric cancer in a high-risk region of China.
AB  - OBJECTIVE: Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle
      of both normal and neoplastic cells. Polymorphism of this gene at codon 242 in
      exon 4 (A870G) has an impact on the risk of several human cancers. The purpose of
      this study was to study the relation between the CCND1 A870G gene polymorphism
      and the risk of non-cardiac gastric cancer in a Chinese population. MATERIAL AND
      METHODS: The study population consisted of 159 patients with non-cardiac gastric
      cancer and 162 cancer-free controls. CCND1 870A/G polymorphism was genotyped by a
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assay and sequencing. RESULTS: CCND1 genotype distribution among the patients was
      significantly different from that among controls; AA (odds ratio (OR)=0.348, 95%
      CI: 0.163-0.742) and GA (OR=0.715, 95% CI: 0.506-1.012) genotypes were
      significantly lower in the gastric cancer patients than in the controls when
      subjects with the GG genotype served as the reference category. In other words,
      the risk of gastric cancer for subjects with the GG genotype was 2.8 times that
      of subjects with the AA genotype, and 1.4 times that of subjects with the GA
      genotype. Furthermore, in the stratification analyses, the risk of GG genotype
      was more evident in subjects >or=60 years of age and those positive for
      Helicobacter pylori (H. pylori) infection. CONCLUSIONS: The CCND1870 GG genotype
      is associated with an increased risk for non-cardiac gastric cancer in patients
      in a high-risk area of China. Larger studies with multiple polymorphisms are
      needed to verify this finding and the function of this polymorphism needs to be
      further investigated.

PMID- 18609127
TI  - Helicobacter pylori infection and short-term intake of low-dose aspirin have
      different effects on alpha-1 antitrypsin/alpha-1 peptidase inhibitor (alpha1-PI)
      levels in antral mucosa and peripheral blood.
AB  - OBJECTIVE: Alpha-1 protease inhibitor (alpha1-PI) is the major circulating serine
      protease inhibitor. The purpose of the study was to investigate alpha1-PI
      expression in gastroduodenal mucosa and blood with respect to two major
      etiological risk factors for gastroduodenal diseases, Helicobacter pylori
      infection and intake of low-dose aspirin. MATERIAL AND METHODS: Twenty volunteers
      (H. pylori-positive and -negative: n=10) received 2 x 50 mg aspirin/day for 7
      days. H. pylori-positive subjects underwent eradication therapy and repeated the
      protocol. Blood and tissue samples were obtained on days 0, 1, 3 and 7; alpha1-PI
      levels were determined by enzyme-linked immunosorbent assay (ELISA) and
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and
      analyzed for histopathological findings. RESULTS: Mucosal alpha1-PI expression
      was between 30 and 75 pg/10 microg total protein in H. pylori-negative subjects,
      and found to be similar in antral, corpus and duodenal mucosa. In H. pylori
      infected subjects, alpha1-PI levels were significantly increased in the antrum
      (mean: 111 versus 37.4 pg/10 microg protein; p=0.019), whereas corresponding
      levels in the corpus, duodenum and sera were unchanged. Alpha-1-PI transcript
      levels were similarly induced in H. pylori-infected subjects (0.13+/-0.15 versus
      0.027+/-0.043 a.u. (arbitrary units), p=0.018). Immunohistochemistry demonstrated
      that infiltrating immune cells and antral surface epithelium contributed to
      elevated alpha1-PI expression in H. pylori-infected subjects. The concomitant use
      of low-dose aspirin did not change mucosal alpha1-PI levels, but led to a 2-fold
      increase in alpha1-PI levels in sera independently of the H. pylori status
      (p<0.009). CONCLUSIONS: Antral alpha1-PI expression is specifically induced by H.
      pylori infection, suggesting a pathophysiological role of this protease inhibitor
      in the upper gastrointestinal tract, whereas low-dose aspirin led to an increase
      in systemic alpha1-PI levels.

PMID- 18609128
TI  - ASAT/ALAT ratio provides prognostic information independently of Child-Pugh
      class, gender and age in non-alcoholic cirrhosis.
AB  - OBJECTIVE: The aspartate amino transferase/alanine amino transferase (ASAT/ALAT)
      ratio is increased in cirrhosis. Some studies indicate that the ratio may provide
      prognostic information as well. The purpose of this study was to further
      elucidate the role of the ASAT/ALAT ratio as a predictor of survival by assessing
      it together with classical risk factors such as age, gender and Child-Pugh (CP)
      class in a mixed cohort of patients with cirrhosis. MATERIAL AND METHODS: Eighty
      nine patients with alcoholic cirrhosis and 81 patients with non-alcoholic
      cirrhosis treated at Aker University Hospital between 1999 and 2004 were
      identified retrospectively. Survival data from these patients per August 2006
      were retrieved from the Norwegian Death Registry. Clinical and biochemical data
      at time of diagnosis were assessed as predictors of survival using the Kaplan
      Meier method and Cox regression models. RESULTS: Median ASAT/ALAT ratio was
      significantly higher in alcoholic cirrhosis (2.42) as compared with non-alcoholic
      cirrhosis (1.42). In both groups, a ratio above the median was predictive of poor
      outcome, p=0.024 and p=0.032, respectively. Other significant predictors of death
      were CP class (p<0.001), clinical decompensation (p<0.001) and age (p=0.001). Cox
      regression analyses showed that the ASAT/ALAT ratio was a predictor of death
      independently of CP class, gender and age in non-alcoholic, but not in alcoholic
      cirrhosis. The estimated increased hazard (risk of dying) in non-alcoholic
      cirrhosis was 5% (CI: 1-8%) per 0.10 increase in ASAT/ALAT ratio. CONCLUSIONS: A
      high ASAT/ALAT ratio is associated with increased mortality in cirrhosis. In non
      alcoholic patients the ratio may provide prognostic information independently of
      classical risk factors.

PMID- 18609129
TI  - Prophylactic antibiotic treatment in acute necrotizing pancreatitis: results from
      a meta-analysis.
AB  - OBJECTIVE: The effect of prophylactic antibiotic treatment on infection and
      survival of acute necrotizing pancreatitis (ANP) remains uncertain. The aim of
      this study was to assess the long-term efficacy of prophylactic antibiotic
      treatment for ANP. MATERIAL AND METHODS: Searches were carried out of electronic
      databases including Medline, EMBASE, the Cochrane Controlled Trials Register, the
      Science Citation Index, and PubMed (updated to December 2007), and manual
      bibliographical searches were also conducted. A meta-analysis of all randomized
      controlled trials (RCTs) comparing prophylactic antibiotic treatment with placebo
      or no treatment was performed. RESULTS: Eight RCTs including 540 patients were
      assessed. The outcomes included infected necrosis, death, non-pancreatic
      infection, surgical intervention, and length of hospital stay. Prophylactic
      antibiotic use leads to a significant reduction of infected necrosis (relative
      risk (RR) 0.69, 95% CI, 0.50-0.95; p=0.02), non-pancreatic infections (RR 0.66
      95% CI, 0.48-0.91; p=0.01), and length of hospital stay (p=0.004) but was not
      associated with a statistically significant reduction in mortality (RR 0.76 95%
      CI, 0.50-1.18; p=0.22) and surgical intervention (RR 0.90 95% CI, 0.66-1.23;
      p=0.52). In a subgroup analysis, carbapenem was associated with a significant
      reduction in infected necrosis (p=0.009) and non-pancreatic infections (p=0.006),
      whereas other antibiotics were not. CONCLUSIONS: Prophylactic antibiotic
      treatment is associated with a significant reduction of pancreatic or
      peripancreatic infection, non-pancreatic infection, and length of hospital stay,
      but cannot prevent death and surgical intervention in acute necrotizing
      pancreatitis.

PMID- 18609130
TI  - Acute edematous and necrotic pancreatitis in a porcine model.
AB  - OBJECTIVE: It is unclear why pancreatitis progresses either to mild edematous
      disease or to severe necrotic disease. The aim of the study was to shed some
      light on this topic by investigating differences during the early stages of
      necrotic and edematous pancreatitis. MATERIAL AND METHODS: Piglets were
      randomized into two groups. Necrotic pancreatitis was induced with retrograde
      injection of 20% taurocholic acid (1 ml/kg), and edematous pancreatitis was
      induced with 0.9% NaCl (1 ml/kg). Central hemodynamics was measured, and
      pancreatic microcirculation was directly examined by intravital microscopy.
      Vascular permeability to proteins and albumin was measured by microdialysis.
      Apoptosis and claudins 2, 3, 4, 5, and 7 were analyzed from pancreatic tissue
      samples. Blood samples were taken for analysis of blood cell counts, blood gases,
      lipase, and amylase. RESULTS: Hemodynamic changes were similar in both groups,
      whereas microcirculatory impairment was more pronounced in necrotic pancreatitis.
      Necrosis was associated only with necrotic pancreatitis. Apoptosis increased only
      in edematous pancreatitis. The number of blood neutrophils and monocytes
      increased and lymphocyte and platelet counts decreased in both groups. Necrotic
      pancreatitis was associated with increased permeability to albumin and proteins.
      Expression of claudins 3, 4, 5, and 7 was not changed during pacreatitis, but in
      acinar cells, membranous expression of claudin-2 increased in both groups.
      CONCLUSIONS: The results show that acute edematous pancreatitis is characterized
      by induction of apoptosis, whereas full-blown pancreatitis is characterized by
      necrosis. Impaired vascular permeability to albumin and protein is related to the
      early phase of necrotic pancreatitis. Claudin-2 increases during acute necrotic
      and edematous pancreatitis and may be related to impaired permeability.

PMID- 18609138
TI  - Reconstitution of stratified murine and human oesophageal epithelia in an in vivo
      transplant culture system.
AB  - OBJECTIVE: The molecular and cellular events responsible for regulating
      development of the oesophageal epithelium are not well understood. At least in
      part, this is due to the lack of a suitable model system with which to study the
      process. Here, we report development of a manipulable in vivo transplant model
      for mouse or human oesophageal epithelium. MATERIAL AND METHODS: Epithelial cells
      were isolated from mouse or human oesophagus and inoculated into de
      epithelialized and devitalized rat tracheas. The rat trachea, containing cells,
      was placed subcutaneously under the dorsal skin of immunodeficient mice. RESULTS:
      We show that a multilayered stratified squamous epithelium can be generated in 4
      6 weeks from as few as 5 x 10(4) isolated oesophageal epithelial cells. The
      reconstituted epithelium recapitulates many of the structural and histological
      features of the normal oesophageal epithelium, including a basal layer of
      cuboidal-like cells, suprabasal layers of differentiating squamous cells and, in
      the case of murine cells, a superficial layer of cornified material. CONCLUSION:
      Our model can be used to generate a multilayered normal murine or human
      epithelium from a single cell suspension of oesophageal epithelial cells. The
      ability to genetically manipulate the cells prior to growth in the model is a
      powerful tool with which to study the molecular mechanisms involved in the
      development of normal oesophagus or in pathogenic processes such as Barrett's
      metaplasia or tumorigenesis.

PMID- 18609139
TI  - Introducing a clinical pathway for acute peptic ulcer bleeding in general
      internal medicine wards.
AB  - OBJECTIVE: Management of acute peptic ulcer bleeding (PUB) is expensive and there
      is little evidence to prove the cost-effectiveness of a clinical pathway. The
      purpose of this study was to introduce a clinical pathway in hospitalized
      patients with acute PUB to evaluate its impact on costs and other outcomes.
      MATERIAL AND METHODS: The clinical pathway was designed for and implemented in
      hospitalized patients, and a physicians reminder system that included chief
      residents, checklists, and case review meetings was also utilized. Use of
      medicine for acid suppression, length of hospital stay (LOS), and treatment costs
      were compared between patients before and after implementation of the clinical
      pathway. Outcome measures included the rate of recurrent bleeding, rate of repeat
      upper gastrointestinal (UGI) endoscopy, and rate of readmission within 30 days of
      discharge. RESULTS: This clinical pathway significantly reduced the use of
      intravenous medicine for acid suppression from 88% to 34%, with mean LOS down
      from 6.7 to 3.6 days, mean cost of medications decreased from New Taiwan Dollars
      (NTD) 8768 to NTD 3940 (cost down 55.1%), mean cost of diagnostic tests lowered
      from NTD 12,560 to NTD 9493 (cost down 24.4%), and mean total hospital cost down
      from NTD 33,142 to NTD 19,519 (cost down 41.1%). Outcome measures were not
      significantly different. CONCLUSIONS: Introduction of a clinical pathway is an
      effective method for reducing costs while maintaining quality of care in the
      management of PUB.

PMID- 18609140
TI  - IL-1beta and IL-8, matrix metalloproteinase 3, and pepsinogen secretion before
      and after H. pylori eradication in gastroduodenal phenotypes.
AB  - OBJECTIVE: Relations between host genetic factors and clinical outcomes of
      Helicobacter pylori infection are variable among ethnicities. The aim of this
      study was to examine gastric mucosal cytokines, matrix metalloproteinase 3 (MMP
      3), and serum pepsinogen levels before and after eradication of H. pylori
      according to IL-1B genotypes and benign gastroduodenal phenotypes in a Korean
      population. MATERIAL AND METHODS: A total of 349 Koreans including H. pylori
      infected subjects (n=230) and H. pylori-negative controls (n=119) were enrolled.
      The former subjects were classified into groups according to the presence of non
      atrophic gastritis (n=74), atrophic gastritis (n=56), gastric ulcer (n=37), and
      duodenal ulcer (n=63). IL-1B polymorphisms were genotyped by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Gastric mucosal IL
      1beta, IL-8, and MMP-3, and serum pepsinogen I and II levels were measured by
      ELISA and radioimmunoassay, respectively. RESULTS: There were no significant
      differences between the IL-1B-31/-511 haplotype (TT/CC, CT/CT, and CC/TT)
      frequencies among the H. pylori-positive and -negative groups. The genotypes of
      IL-1B-31/-511 polymorphisms did not affect clinical phenotypes, inflammatory
      cytokines, MMP-3, and pepsinogen secretion. Subjects with H. pylori-infected
      atrophic gastritis exhibited significantly higher basal levels of cytokines and a
      lower pepsinogen I/II ratio than those of other groups. Following H. pylori
      eradication, inflammatory cytokines significantly decreased and the pepsinogen
      I/II ratio increased in all groups. CONCLUSIONS: Mucosal inflammatory cytokines,
      MMP-3, and pepsinogen secretion are related to gastroduodenal phenotypes but not
      to IL-1B genotypes. Eradication of H. pylori can reduce mucosal inflammation and
      restore pepsinogen secretion.

PMID- 18609141
TI  - Plasma glucagon-like peptide 1 and peptide YY levels are not altered in
      symptomatic fructose-sorbitol malabsorption.
AB  - OBJECTIVE: Carbohydrate malabsorption causes more symptoms in patients with
      functional gastrointestinal disorders than in healthy individuals. The purpose of
      this study was to investigate whether this could be explained by differences in
      ileal brake hormone secretion. MATERIAL AND METHODS: Eighteen consecutive
      patients with functional abdominal complaints, referred to our clinic for
      investigation of self-reported food hypersensitivity, were included in the study
      and compared with 15 healthy volunteers. All subjects ingested a mixture of 25 g
      fructose and 5 g sorbitol. Pulmonary hydrogen and methane excretion and plasma
      glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) levels were measured during
      the next 3 h. Both habitual and post-test symptoms were assessed. RESULTS:
      Malabsorption of fructose and sorbitol was present in 61% of the patients and 73%
      of the controls. Nevertheless, the patients experienced significantly more
      symptoms following carbohydrate challenge, and 78% of the patients claimed that
      the challenge replicated their habitual gastrointestinal complaints. No
      significant differences in gas excretion or GLP-1 and PYY levels were found
      between patients and controls or between symptomatic and asymptomatic
      carbohydrate malabsorbers. A weak correlation between hydrogen excretion and PYY
      levels was demonstrated in non-producers of methane. CONCLUSIONS: Neither
      intestinal gas production nor ileal brake hormone secretion seems to play a role
      in the symptomatology of carbohydrate intolerance in patients with self-reported
      food hypersensitivity. Other mechanisms related to bacterial fermentation may be
      involved and should be investigated further.

PMID- 18609142
TI  - Inflammatory markers neopterin and alanine aminotransferase in HCV patients
      treated with HCV NS3.4A protease inhibitor telaprevir (VX-950) and/or
      peginterferon alfa-2a.
AB  - OBJECTIVE: Neopterin is a marker of monocyte/macrophage activity. Alanine
      aminotransferase (ALAT) is a marker of hepatocyte injury. The aim of this study
      was to determine changes in neopterin and ALAT levels, as markers of
      inflammation, in two ancillary studies during two-phase 1b trials of hepatitis C
      virus (HCV) NS3.4A protease inhibitor telaprevir (VX-950), with or without
      peginterferon alfa-2a (Peg-IFN). MATERIAL AND METHODS: Fifty-four chronic
      hepatitis C patients (genotype 1) received placebo or telaprevir, with or without
      Peg-IFN, for 14 days in two multiple-dose studies. RESULTS: During administration
      of telaprevir, every patient demonstrated a >2-log decrease in HCV RNA. Mean
      neopterin and ALAT levels decreased in all four groups receiving telaprevir
      alone. In contrast, mean neopterin levels increased and ALAT levels decreased in
      the Peg-IFN plus telaprevir and Peg-IFN plus placebo groups. CONCLUSIONS: These
      data suggest that treatment of chronic hepatitis C patients with an HCV NS3.4A
      protease inhibitor ameliorates inflammation. The increase in neopterin levels and
      the decrease in ALAT levels during administration of Peg-IFN with or without
      telaprevir are in accordance with earlier observations showing that IFN reduces
      hepatocyte injury but increases monocyte/macrophage activity. The IFN-mediated
      immunomodulatory effects appear to remain intact when IFN is combined with
      telaprevir.

PMID- 18609143
TI  - Effect of smoking on gastric histology in Helicobacter pylori-positive gastritis.
AB  - OBJECTIVE: Smoking and Helicobacter pylori are both deleterious to the gastric
      and duodenal mucosa. Smoking also seems to modify inflammation in H. pylori
      infection. The aim of this study was to investigate the relationship between
      smoking and H. pylori in the Finnish population. MATERIAL AND METHODS: We
      analysed the effect of smoking on gastric inflammation, humoral response to H.
      pylori and peptic ulcer disease among 318 Finnish H. pylori-positive patients
      (age 18-75 years; 73 smokers). Gastric histology was evaluated according to the
      updated Sydney system. RESULTS: Smoking affected neither antral inflammation nor
      atrophy. In the gastric body, smokers showed milder chronic and neutrophilic
      inflammation and less atrophy (4% versus 17%, p=0.004). In smokers, H. pylori
      infiltration was denser in the atrium (mean 2.14 versus 1.87, p=0.02) but less
      dense in the body (mean 1.55 versus 1.84, p=0.003). Smoking thus seems to
      decrease inflammation in the gastric body and to delay atrophic changes in the
      gastric body. Subsequently, the prevalence of duodenal ulcers increased (32%
      versus 11%, p<0.001), but not the prevalence of gastric ulcers. Smoking also
      reduced serum IgG antibody titres against H. pylori (mean 8535 versus 5587,
      p=0.002) and their percentage decrease after successful eradication, possibly
      affecting serological diagnostic efficacy. Smokers were younger than non-smokers,
      but when age was taken into account, the differences remained the same.
      CONCLUSIONS: In H. pylori-positive gastritis, smoking reduced inflammation and
      atrophy in the gastric body as well as humoral response to H. pylori.

PMID- 18609144
TI  - Nine-year follow-up of a patient with attenuated familial adenomatous polyposis
      treated with cyclo-oxygenase-2 inhibitors.
AB  - Familial adenomatous polyposis (FAP) is caused by germline mutations in the
      adenomatous polyposis coli (APC) gene with onset of florid polyposis in childhood
      and development of colorectal cancer by age 30. Colectomy is advised because of
      the high risk of developing colorectal cancer. Attenuated FAP (AFAP) is a variant
      of this condition with a later age of onset and milder clinical phenotype;
      however, colectomy is advised once polyposis develops and polyps cannot be
      managed endoscopically. We report a case of a patient with AFAP and previously
      resected colonic carcinoma that was treated with chemoprophylaxis with long-term
      cyclooxygenase-2 (COX-2) inhibitors after declining colectomy. Colonoscopic
      examination demonstrated regression of polyps by 18 months. After 9 years of
      follow-up, there was no evidence of colorectal cancer development or progression
      of polyposis. This is the first case report on long-term treatment with COX-2
      inhibition in a patient with AFAP and previous colonic carcinoma.

PMID- 18609146
TI  - Characteristics of intestinal tuberculosis in ultrasonographic techniques.
AB  - OBJECTIVE: There is a paucity of data on the sonographic criteria for the
      diagnosis of intestinal tuberculosis. The purpose of this study was to further
      characterize the potential sonographic signs of intestinal tuberculosis and to
      increase the diagnostic sensitivity and specificity of ultrasound. MATERIAL AND
      METHODS: Seven patients with a final diagnosis of gastrointestinal tuberculosis
      and a control group of 18 patients suffering from tuberculosis limited to the
      lungs were prospectively evaluated for sonographic criteria of intestinal
      tuberculosis and the findings were compared with those in 50 healthy controls.
      RESULTS: The following signs of intestinal tuberculosis were detectable:
      asymmetric thickened bowel wall (100%), intramural abscesses (86%), fistula
      (43%), extramural abscesses (29%), mesenteric thickening (29%), "white bowel"
      sign (29%), hypoechoic edema of Kerckring's folds with mesenterial thrombosis
      (14%), enlarged mesenteric lymph nodes with inhomogeneous echotexture and
      circumscribed hypoechoic spots <3 mm (86%), ascites (29%) and enlarged spleen
      (14%). These signs were exclusively present in patients with intestinal
      tuberculosis as compared with patients with tuberculosis limited to the lungs or
      with healthy controls. We could confirm the endoscopically reported right-sided
      prevalence of these wall thickenings. In contrast to the reported literature, a
      much higher prevalence of these sonographic signs was found as they were present
      in all patients. Six of 7 patients (86%) showed enlarged mesenteric lymph nodes.
      This was particularly interesting as mesenteric lymph nodes have not been
      described as being enlarged in the majority of other differential diagnoses of
      the ileocecal region. CONCLUSIONS: The combination of bowel-wall thickening of
      the ileocecal region with intramural abscesses with or without fistula, abscesses
      and mesenteric thickening accompanied by enlarged mesenteric lymph nodes was
      highly predictive of intestinal tuberculosis.

PMID- 18609148
TI  - Prognosis following endoscopic injection sclerotherapy for esophageal varices in
      adults: 20-year follow-up study.
AB  - OBJECTIVE: Endoscopic injection sclerotherapy (EIS) is beneficial in the
      management of active hemorrhaging and prevention of recurrent bleeding from
      esophageal varices. However, its long-term efficacy and safety are poorly
      defined. The aim of this study was to determine long-term cumulative survival and
      clarify negative predictive factors for survival following EIS in patients with
      esophageal varices. MATERIAL AND METHODS: Between 1981 and 1987, 72 patients were
      prospectively enrolled in a post-EIS follow-up program. Variceal rebleeding,
      recurrence, and survival were recorded in follow-up examinations conducted for up
      to 20 years. RESULTS: The mean follow-up period was 86.9 months. The cumulative
      survival rates were 65.2%, 53.6%, 26.1%, and 11.6% at 36, 60, 120, and 240
      months, respectively, with liver failure the most common cause of death.
      Esophageal varices were eradicated in 93.1% of the patients following EIS and no
      recurrence of varices was seen beyond 7 years. Significant negative predictive
      factors for survival rate shown by Cox's proportional multivariate hazard model
      analysis were older age, advanced liver damage, presence of hepatocellular
      carcinoma, and occurrence of rebleeding. CONCLUSIONS: Long-term survival,
      rebleeding, and recurrence rates following EIS were clarified. Furthermore, our
      results clearly demonstrate negative predictive factors for survival after EIS.

PMID- 18609149
TI  - An unusual endoscopic diagnosis for acute epigastric pain.

PMID- 18609150
TI  - Unkilned and large amounts of oats in the coeliac disease diet: a randomized,
      controlled study.
AB  - OBJECTIVE: There is evidence for the long-term safety of oats as part of a gluten
      free diet in coeliac disease (CD). Oats is generally processed by kilning, which
      theoretically may change its antigenic properties and be the reason that it is
      tolerated by patients with CD. The aim of this study was to investigate the
      suitability of large amounts of unkilned oats, comparing its use with kilned oats
      in adult coeliac patients. MATERIAL AND METHODS: The study group included 13 men
      and 19 women with CD in remission. The goal of daily intake of oats was 100 g
      during one year. These patients using oats as part of their gluten-free diet were
      randomized to two treatment groups. One group used regular oats and the other
      unkilned oats. After 6 months the patients changed the treatment groups. Food
      intake, symptoms, histology of the small intestine and the levels of endomysial
      antibodies were noted. RESULTS: No marked changes were found in the duodenal
      biopsies, in the levels of endomysial antibodies or in the well-being of the
      patients. Compliance with the diet did not change during the follow-up.
      CONCLUSIONS: Large amounts of both unkilned and regular kilned oats are well
      tolerated by adult patients with CD. Oats is therefore not harmful, even in its
      unkilned form, which indicates that its antigenic nature is not changed by common
      industrial food processing in such a way that would prevent the provoking of CD.

PMID- 18609151
TI  - Indolent fever, weight loss and spleen infiltrate.
AB  - This is a case of a young female who was admitted to our department with fever of
      one month in duration, without a specific pattern, anemia, lymphadenopathy and
      weight loss. The initial clinical and radiological evaluation and laboratory
      tests, although extensive, were unrevealing. The patient's general situation was
      temporarily improved and she was dismissed, but she revisited our hospital 2, 5
      months later because of fever recurrence and a new pain at the upper left
      abdomen. This time the pathological findings were more prominent. The abdomen CT
      scan revealed a splenic mass. The evidence was suggestive of lymphoma,
      granulomatous or unusual infectious disease. However, it was not possible to
      establish a certain diagnosis, so we proceeded to open splenectomy and
      histological analysis that disclosed an inflammatory pseudotumor of the spleen.
      This procedure apart from diagnostic proved to be also therapeutic. The patient
      was cured and at six-month follow up she was in perfect health. Our case suggests
      that a high index of suspicion regarding this entity is needed, particularly if
      the disease course is variable and protracted.

PMID- 18609153
TI  - Terlipressin-induced ventricular arrhythmia.
AB  - During intravenous treatment with terlipressin for recurrent gastrointestinal
      (GI) bleeding, a 50-year-old male with no history of heart disease developed a
      newly prolonged QT interval and torsade de pointes. Risk factors present for
      acquired long QT syndrome were mineral dysbalance and a history of alcohol abuse
      with hepatic impairment. The patient was brought back to a normal sinus rhythm
      after a single 300-J counter-shock. Terlipressin was discontinued, and the
      patient's QTc interval subsequently returned to baseline. During 6 weeks of
      monitoring, arrhythmia did not recur.

PMID- 18609154
TI  - Decreased death from gastric cancer by endoscopic screening: association with a
      population-based cancer registry.
AB  - OBJECTIVE: To determine death rates from gastric cancer when using endoscopic
      screening. MATERIAL AND METHODS: In this historical cohort study comprising
      11,763 participants aged from 40 to 75 years without gastric disorders between
      1990 and 1992, 2192 were examined by gastric endoscopy while 9571 were not
      examined by endoscopy or X-ray. The relative risk of gastric cancer death was
      compared between the two groups. RESULTS: When screened with endoscopy, 41
      patients were diagnosed with gastric cancer and the ratio of early cancer was
      78%. On matching the population-based cancer registry (the Fukui Cancer
      Registry), 63 patients in the examined group were diagnosed with gastric cancer
      within 10 years after the initial screening including the above 41 patients. In
      the non-examined group, 147 patients were diagnosed with gastric cancer in the
      same period. In the examined and non-examined groups, 5 and 63 patients,
      respectively, died from gastric cancer. The relative risk for gastric cancer
      death in the examined group was 0.3465 (95% CI: 0.1396-0.8605) when compared with
      the non-examined group. For male patients, the relative risk was 0.2174 (95% CI:
      0.0676-0.6992). CONCLUSIONS: The death rate from gastric cancer decreased when
      endoscopic screening was used. Endoscopy is recommended as a population-based
      screening method for gastric cancer in regions or countries where mortality from
      this disease is high.

PMID- 18609155
TI  - Central neuronal mechanisms of gastric electrical stimulation in diabetic
      gastroparesis.
AB  - OBJECTIVE: The mechanisms underlying symptom improvement in gastric electrical
      stimulation (GES) are not fully understood. Modulation of the central nervous
      system excitability may be involved. The objective of the study was to
      investigate the central effects of GES, including the possible modulation of the
      visceral sensory nervous system. MATERIAL AND METHODS: A gastric electrical
      stimulator was implanted in seven diabetic patients with medically refractory
      gastroparesis. A double-blinded protocol was used to investigate the patients at
      baseline and one month after recovery with the stimulator turned on and off (1
      month periods). The following assessments were carried out: mechanical, thermal
      and electrical stimulations with sensory recordings in the esophagus and
      duodenum, and standardized, self-administered, daily symptom questionnaires.
      RESULTS: No difference was found between baseline and the on- and off periods in
      overall gut pain thresholds across all stimulus modalities in the esophagus
      (p=0.63), duodenum (p=0.19) or esophagus and duodenum combined (p=0.76). No
      difference in the sensory response to mechanical stimulation was found in the
      esophagus before (all p>0.31) and after (all p>0.43) smooth muscle relaxation
      with butylscopolamine. Similar findings were observed in the duodenum. No
      differences were found in thermal sensitivity (esophagus (p=0.67) and duodenum
      (p=0.17)), sensory response to electrical stimulation (esophagus (p=0.57) and
      duodenum (p=0.52)) or induced somatic referred pain areas (esophagus (p=0.75) and
      duodenum (p=0.51)). No difference was seen in the induced somatic referred pain
      areas or self-reported symptoms. CONCLUSIONS: No evidence was found for GES
      induced modulation of the visceral sensory system and central excitability.
      However, GES has been proven to modulate the central nervous system in animal
      studies, necessitating further human experiments in order unambiguously to
      establish the possible central effects of GES.

PMID- 18609156
TI  - Mycobacterium avium subspecies paratuberculosis and Crohn's disease granulomas.
AB  - OBJECTIVE: Chronic infection with Mycobacterium avium subspecies paratuberculosis
      (M. paratuberculosis) has been proposed as a cause of Crohn's disease. Although
      numerous investigators have examined the link between M. paratuberculosis and
      Crohn's disease, the evidence remains controversial. The aim of this study was to
      examine intestinal granuloma from Crohn's patients for M. paratuberculosis using
      a semi-nested M. paratuberculosis-specific IS900 polymerase chain reaction (PCR).
      MATERIAL AND METHODS: Paraffin-embedded ileal or colonic tissues of patients with
      Crohn's disease were analyzed. Microdissection of this tissue into "granulomas"
      and "not granulomas" was performed. On the basis of sequences reported in GenBank
      alignments, we designed primer sets specific for M. paratuberculosis. The
      presence of the M. paratuberculosis was examined by semi-nested IS900-specific
      PCR with human beta-actin gene as a control for DNA quality. RESULTS: Biopsies
      from 20 Crohn's patients were examined. Human beta-actin gene was amplified in
      all samples. M. paratuberculosis DNA was detected in the microdissected granuloma
      in 1 (5%) patient with Crohn's disease and in none of the "not granuloma"
      tissues. CONCLUSIONS: M. paratuberculosis DNA can rarely be detected within
      Crohn's granuloma. These results do not support M. paratuberculosis as the
      primary etiology of Crohn's disease.

PMID- 18609157
TI  - Is there a role for routine duodenal biopsy in diagnosing giardiasis in a
      European population?
AB  - OBJECTIVE: Giardia lamblia is the most common enteric protozoan world-wide. The
      prevalence varies internationally. Patients with giardiasis typically have
      diarrhoea but may have atypical symptoms when referred for endoscopy. The purpose
      of this study was to investigate whether a policy of routine duodenal biopsies
      increased the yield of diagnosing Giardia and whether treatment improved the
      patient's presenting symptoms. MATERIAL AND METHODS: Our hospital endoscopy
      database was examined retrospectively, from January 2003 to January 2004, to
      identify patients who had undergone gastroscopy and targeted duodenal biopsies.
      Thereafter, routine duodenal biopsies were carried out prospectively on
      unselected adult patients referred for gastroscopy from January 2004 to April
      2006. Patients diagnosed with Giardia were assessed for symptoms and response to
      treatment. RESULTS: In the retrospective group, of the 5979 gastroscopies
      performed, 1464 duodenal biopsies were carried out; 5 patients had giardiasis, a
      prevalence of 0.08%, CI 0.01-0.16%. In the prospective group, 2000 gastroscopies
      with duodenal biopsies were performed; 9 patients had giardiasis, a prevalence of
      0.45%, CI 0.16-0.74%. The difference in prevalence was 0.37%, CI 0.06-0.67%,
      which was statistically significant with a Yates' chi(2)(CC) of 9.49, p<0.005. On
      comparing response to treatment, the Fisher exact test revealed a proportional
      difference that was not statistically significant. CONCLUSIONS: In a UK
      population, the prevalence of Giardia was low. Although a policy of routine
      duodenal biopsy resulted in more cases of Giardia being identified, this increase
      in detection did not correspond with an improvement in patients' symptoms. This
      suggests that Giardia may be a coincidental finding. This study does not support
      the approach of routine duodenal biopsy in diagnosing giardiasis.

PMID- 18609159
TI  - Gastrointestinal involvement in Henoch-Schonlein purpura.
AB  - OBJECTIVE: To analyse the gastrointestinal manifestation of Henoch-Schonlein
      purpura (HSP) in adult patients, including clinical and endoscopic features.
      MATERIAL AND METHODS: Patients with a final diagnosis of HSP admitted from
      January 1995 to January 2006 were included. Their medical records, including
      clinical presentation, laboratory data, endoscopy and pathology reports, were
      reviewed retrospectively. RESULTS: One-hundred-and-fifteen patients were
      included. Gastrointestinal symptoms occurred in 90 patients (78.2%), with
      abdominal pain the most common symptom. Fifty-four patients underwent
      gastroscopy, while 24 underwent colonoscopy. The endoscopic lesions included
      mucosal erythema, oedema, multiple irregular ulcers and nodular changes. In the
      upper GI tract, the second portion of the duodenum was the most frequently
      involved area and is where the most severe lesions occur. In the lower GI tract,
      the rectum was the most frequently involved area, but the most severe lesions
      were found in the terminal ileum. CONCLUSIONS: HSP may present with acute abdomen
      without typical skin manifestations, and gastroscopy and colonoscopy can be
      helpful in the early diagnosis of HSP in these patients. Typical endoscopic
      findings include diffuse mucosal oedema, erythema, petechia or multiple irregular
      ulcers, especially in the second portion of the duodenum or in the terminal
      ileum.

PMID- 18609160
TI  - Patients with cyclic vomiting pattern and diabetic gastropathy have more
      migraines, abnormal electrogastrograms, and gastric emptying.
AB  - OBJECTIVE: Some patients with diabetic gastroparesis exhibit cyclical symptoms.
      The purpose of this work was to study the subset of patients with cyclic vomiting
      characteristics, described as a cyclic vomiting pattern, in a population of
      patients with symptoms of diabetic gastroparesis. MATERIAL AND METHODS: Sixty
      seven patients with symptoms of diabetic gastroparesis were investigated. The
      patients were divided into two groups based on the presence or lack of cyclic
      symptoms, and stratified by demographics, medical history, hemoglobin A1C, total
      symptom score (TSS), standardized gastric emptying test (GET), and
      electrogastrography (EGG). RESULTS: Of these 67 patients, 38 (56%) had cyclic
      symptoms. The two groups were similar in age, gender, illness duration, insulin
      use, hemoglobin A1C values, and TSS. There were noteworthy differences regarding
      migraine headache (47.4% versus 20.7%, p=0.02), gastric emptying study (GES) at 1
      h (84.1% versus 59.9%, p=0.02), EGG frequency (4.9 versus 3.6 cpm, p=0.05), and
      gastric emptying area under the curve (p=0.06). CONCLUSIONS: A sizeable
      percentage of patients have cyclic symptom patterns and have a higher incidence
      of migraine headaches, a greater delay in gastric emptying, and more abnormal EGG
      frequencies than other patients with symptoms of diabetic gastroparesis.

PMID- 18609161
TI  - Helicobacter pylori infection in children with celiac disease.
AB  - OBJECTIVE: To analyze the prevalence of Helicobacter pylori (H. pylori) infection
      in children with celiac disease (CD) and to examine the role of H. pylori
      infection in clinical, laboratory and histopathological presentations of CD.
      MATERIAL AND METHODS: Data on 96 children with CD and 235 children who underwent
      endoscopy were compared for the prevalence and gastric histology pattern of H.
      pylori. Clinical presentation, laboratory and histological findings of CD
      children with and without H. pylori infection were compared. RESULTS: Twenty-one
      subjects (21.8%) in the CD group and 56 subjects (23.8%) in the control group had
      H. pylori gastritis. Gastric metaplasia is higher in CD patients with H. pylori
      gastritis (19%) than in patients without H. pylori gastritis (1.3%) and in the
      control group (3.5%) (p<0.05 for all groups). Abdominal distension is more common
      at initial admission in CD patients with H. pylori gastritis (57.1% versus 14.6%,
      p<0.05). No significant difference was found between H. pylori (+) and (-) CD
      patients in terms of prevalence of anemia, iron deficiency and iron-deficiency
      anemia. Only mild duodenal histological findings were more common in H. pylori
      patients (57.1% versus 26.7%, p<0.05). CONCLUSIONS: CD may be associated with H.
      pylori gastritis, but it does not affect the clinical presentation of the
      disease, except for abdominal distension; CD is associated with mild duodenal
      lesions. A gluten-free diet improves the symptoms in all patients independently
      of the presence of H. pylori gastritis. Gastric metaplasia increases in the
      presence of H. pylori gastritis. Further prospective studies are needed to
      examine the clinical and histopathological outcomes of gastric metaplasia
      associated with H. pylori gastritis in CD patients.

PMID- 18609162
TI  - Plasma ADAMTS13 activity parallels the APACHE II score, reflecting an early
      prognostic indicator for patients with severe acute pancreatitis.
AB  - OBJECTIVE: Severe acute pancreatitis (SAP) frequently progresses to pancreatitis
      associated multiorgan failure (MOF) with high mortality. Decreased plasma
      ADAMTS13 activity (ADAMTS13:AC) results in the accumulation of unusually large
      von Willebrand factor multimers (UL-VWFM) and the formation of platelet thrombi,
      ultimately leading to MOF. The purpose of the study was to investigate the
      potential role of ADAMTS13:AC in the severity of SAP. MATERIAL AND METHODS:
      Plasma ADAMTS13:AC and its related parameters were sequentially determined in 13
      SAP patients. ADAMTS13:AC was determined by the chromogenic act-ELISA. RESULTS:
      Within 1 or 2 days after admission, ADAMTS13:AC was lower in SAP patients (mean
      28%) than in healthy controls (99%), and gradually recovered in the 11 survivors
      but further decreased in the 2 non-survivors. Patients with higher sepsis-related
      organ failure assessment (SOFA) scores showed lower ADAMTS13:AC than those
      without these scores. The inhibitor against ADAMTS13 was undetectable. On day 1,
      von Willebrand factor antigen (VWF:Ag) was higher (402%, p<0.001) in SAP patients
      than in controls (100%). VWF:Ag gradually decreased in the survivors, except in
      the 3 patients needing a necrosectomy, but remained high in the non-survivors.
      ADAMTS13:AC was inversely correlated with the APACHE II score (r=-0.750,
      p<0.005), and increased plasma concentrations of interleukin 6 (IL-6) and IL-8 at
      admission. UL-VWFM-positive patients had lower ADAMTS13:AC and decreased serum
      calcium concentrations, but higher VWF:Ag and IL-8 concentrations than UL-VWFM
      negative patients. CONCLUSIONS: Plasma ADAMTS13:AC was closely related to the
      APACHE II score. This intimate relationship may serve as an early prognostic
      indicator for SAP patients. The imbalance between decreased ADAMTS13:AC and
      increased UL-VWFM could contribute to SAP pathogenesis through enhanced
      thrombogenesis.

PMID- 18609163
TI  - Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a
      nationwide study.
AB  - OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic liver disease, which if
      untreated can lead to cirrhosis and hepatic failure. The aim of the study was to
      investigate the incidence, prevalence, diagnostic tradition and clinical initial
      presentation of AIH. MATERIAL AND METHODS: Analyses were performed in 473
      patients identified as having probable or definite AIH. RESULTS: The incidence of
      AIH was 0.85/100,000 (95% CI 0.69-1.01) inhabitants, which is somewhat lower than
      reported previously. The point prevalence amounted to 10.7/100,000 (95% CI 8.8
      13.1), and 76% of the cases were females. The age-related incidence curve was
      bimodal but men were found to have only one incidence peak in the late teens,
      whereas women had a peak after menopause. AIH was presented as a spectrum of
      clinical settings from detected "en passant" to acute liver failure. Almost 30%
      of patients already had liver cirrhosis at diagnosis. Autoantibodies indicative
      of AIH type 1 were found in 79% of cases. Other concomitant autoimmune diseases
      were frequently found (49%). CONCLUSIONS: The incidence and prevalence figures
      confirm that AIH is a fairly uncommon disease in the Swedish population. Symptoms
      at presentation were unspecific, but almost half of the patients were jaundiced,
      with around 30% having liver cirrhosis. The majority of Swedish AIH patients had
      AIH type 1.

PMID- 18609164
TI  - Perihilar lymph nodes in patients with primary sclerosing cholangitis with and
      without cholangiocellular carcinoma.
AB  - OBJECTIVE: Enlarged perihilar lymph nodes have been described in patients with
      primary sclerosing cholangitis (PSC). The aim of the study was to determine the
      clinical relevance of perihilar lymph nodes in PSC patients with and without
      cholangiocellular carcinoma (CCC). MATERIAL AND METHODS: The status of perihilar
      lymph nodes was investigated in 117 patients with PSC using "high-end"
      ultrasound. Thirty-five of the 117 PSC patients had histologically proven CCC.
      Lymph node status was correlated with the presence of CCC and inflammatory bowel
      disease (IBD). RESULTS: Seventy-three percent of PSC patients without CCC and 86%
      of patients with CCC had enlarged perihilar lymph nodes (NS). In CCC patients,
      the width of lymph nodes was significantly larger (12+/-6 mm versus 8+/-4 mm;
      p=0.0001), and the length:width ratio (2.15+/-0.7:1 versus 2.5+/-0.6:1; p=0.004)
      of the lymph nodes was significantly lower. Thirty-seven percent of PSC patients
      without CCC and 57% of patients with PSC and CCC had multiple perihilar lymph
      nodes (p=0.04). In all patients, the presence versus absence of IBD had no
      influence on the number (84% versus 74%,) and size of perihilar lymph nodes
      (length: 21+/-10 mm versus 19+/-7 mm). Lymph node status did not correlate with
      the number of episodes of cholangitis. CONCLUSIONS: Enlarged perihilar lymph
      nodes are characteristic of patients with PSC. Since perihilar lymph nodes are
      not predictive of the presence of complicating CCC, such patients should not be
      excluded from liver transplantation.

PMID- 18609165
TI  - Small intestinal bacterial overgrowth.
AB  - Small intestinal bacterial overgrowth (SIBO) syndrome is characterized in its
      florid form by diarrhoea and weight loss. The most common underlying factors are
      dysmotility, small intestinal obstruction, blind or afferent loops. Small
      intestinal bacterial overgrowth can be diagnosed by: 1) culture of jejunum
      aspirate for bacterial counts, 2) 14C-D-xylose breath testing, 3) non-invasive
      hydrogen breath testing using glucose or lactulose or 4) 14C-glycocholic acid
      breath testing. The treatment usually consists of the eradication of bacterial
      overgrowth with repeated course of antimicrobials, correction of associated
      nutritional deficiencies and, when possible, correction of the underlying
      predisposing conditions.

PMID- 18609166
TI  - Clinical symptoms in celiac patients on a gluten-free diet.
AB  - OBJECTIVE: Persistent villous atrophy in patients with celiac disease (CD) on a
      gluten-free diet (GFD) is reported with increasing frequency. The aim of this
      study was to evaluate a possible association between persistent damage of the
      villi and "atypical" gastrointestinal symptoms in CD patients on a GFD. MATERIAL
      AND METHODS: Sixty-nine CD patients on a GFD were divided into two groups: Group
      A included 42 patients (6 M, 36 F, age range 17-62 years) undergoing
      esophagogastroduodenoscopies (EGDs) due to the presence of symptoms; Group B
      included 27 control patients (6 M, 21 F, age range 24-71 years) who were
      asymptomatic at the time of the study. Both groups underwent EGDs and a duodenal
      histologic study. RESULTS: Persistent endoscopic lesions were more frequent in
      Group A (30/42) than in Group B (12/27; p=0.01). Villous atrophy was
      significantly more frequent in Group A than in Group B: 85% versus 33% (p<0.0001;
      odds ratio (OR)=12; 95% CI 3.7-38.9). Gastrointestinal symptoms in the Group A
      patients were different from those present at CD diagnosis:
      anemia/diarrhea/weight loss in 6 cases; gastroesophageal reflux disease (GERD)
      like symptoms in 12 cases; abdominal pain/constipation in 24 cases. In Group A
      there was no difference in gender distribution, age and duration of GFD between
      subjects with normal villi and those with persistent partial villous atrophy.
      Patients with persistent symptoms showed a higher intraepithelial eosinophil
      count (p=0.005) than the asymptomatic patients (p=0.01). CONCLUSIONS: Persistent
      intestinal villous atrophy in CD patients on a GFD is associated with
      gastrointestinal symptoms considered "atypical" for CD and not present at CD
      diagnosis.

PMID- 18609167
TI  - Can primary hypolactasia manifest itself after the age of 20 years? A two-decade
      follow-up study.
AB  - OBJECTIVE: The age at manifestation of primary hypolactasia varies between ethnic
      groups. Many people report experiencing the first symptoms of lactose intolerance
      at adult age. The purpose of this study was to investigate whether primary
      hypolactasia can appear after the age of 20 among the Finnish population and to
      investigate the outcome of different diagnostic methods of lactose maldigestion.
      MATERIAL AND METHODS: Lactose digestion status was assessed by the lactose
      tolerance test with ethanol (LTTE) in 42 subjects (38-71 years) who reported
      having gastrointestinal symptoms after the ingestion of 20 g or less of lactose
      and who were diagnosed as lactose digesters in earlier studies. Thirteen of the
      study subjects underwent upper gastrointestinal endoscopy, and 35 gave a blood
      sample for DNA analysis. RESULTS: Only one of the 42 subjects studied had the
      genotype C/C(-13910) indicating hypolactasia. Lactase activity was higher in
      those with the genotype T/T (69.2 U/g protein) than in those with the
      heterozygous genotype C/T (36.3 U/g protein) (p=0.017). CONCLUSIONS: Although
      primary hypolactasia normally appears before the age of 20 years, the decline in
      lactase activity may on rare occasions continue after that age. Genotyping of the
      C/T(-13910) variant was found to be a reliable diagnostic approach in defining
      the lactase persistence/non-persistence status of the study subjects.

PMID- 18609169
TI  - Serum biomarkers for atrophic gastritis and antibodies against Helicobacter
      pylori in the elderly: Implications for vitamin B12, folic acid and iron status
      and response to oral vitamin therapy.
AB  - OBJECTIVES: To investigate the prevalence of serological markers for chronic
      atrophic gastritis (AG) and Helicobacter pylori antibodies (HPAb) in an elderly
      population, and to examine the interrelationship and significance for cobalamin,
      folic acid and iron status and response to oral vitamin therapy. MATERIAL AND
      METHODS: The study included community-dwelling subjects (n=209), mean age 76
      years, randomized to 4 month of oral daily treatment with 0.5 mg cyanocobalamin,
      0.8 mg folic acid and 3 mg vitamin B(6) or placebo (double-blind). Biochemical
      tests were carried out before and after treatment. RESULTS: AG, as indicated by a
      pepsinogen I/II ratio <2.9, occurred in 14% (26/190) and HPAb in 54% (102/190) of
      the subjects. AG subjects had higher levels of serum methylmalonic acid (MMA)
      (p<0.001), plasma homocysteine (tHcy) (p<0.05), lower haemoglobin (Hb) (p<0.01)
      and a higher prevalence of vitamin B(12) deficiency (p<0.01). HPAb was associated
      with AG, whereas AG subjects without HPAb had higher tHcy and MMA levels. There
      was no correlation between AG and iron status. Oral vitamin treatment led to
      greater (albeit non-significant) improvements in MMA, tHcy and total cobalamins
      in AG subjects compared to non-AG subjects. CONCLUSIONS: AG is a common condition
      and is a significant determinant of vitamin B(12) status. AG is correlated to
      HPAB and lower Hb. Elderly AG subjects respond at least as well as non-AG
      subjects to oral treatment with B-vitamins in the doses employed.

PMID- 18609170
TI  - Endoscopic retrograde cholangiography in the diagnosis and treatment of
      mucobilia.
AB  - OBJECTIVE: Some biliary neoplasms secrete copious mucin into bile ducts, yet the
      management of mucobilia is not well known. The objective of this study was to
      analyze 16 patients with copious mucin in the biliary tract stressing the
      diagnostic and therapeutic aspects of endoscopic retrograde cholangiography
      (ERC). MATERIAL AND METHODS: Sixteen patients with mucobilia were found among
      5635 cases of ERC from October 1999 to October 2006 in our institution.
      Diagnostic and therapeutic ERC as well as clinical features were retrospectively
      analyzed. RESULTS: Mucin had a greater impact than the neoplasm itself on the
      cholangiogram and clinical presentation. ERC failed to show the tumors but a
      disproportionate or aneurysmal dilatation of the segmental or lobar duct
      correlated with the tumor-bearing duct was evident. Endoscopic managements
      included clearance of intraductal mucin and/or endoscopic nasobiliary drainage
      (ENBD). Three patients were excluded from outcome assessment because of non
      specific symptoms or spontaneously subsiding jaundice. Among the 13 patients
      eligible for assessment, subjective improvement in symptoms and/or a decrease in
      jaundice along with subsiding cholangitis following ERC was observed in 5 of the
      7 patients that underwent both clearance of intraductal mucin and ENBD (ENBD
      function was poor in all 7 patients), in 1 patient who underwent only clearance
      of intraductal mucin, and in 3 of the 5 patients who underwent only ENBD. The
      three patients with progressive jaundice, despite endoscopic management, had
      advanced disease. CONCLUSIONS: ERC revealed the tumor-bearing duct but not the
      extent of the disease in most of the patients with mucobilia. When mucobilia is
      encountered during ERC, the management should include clearance of as much
      intraductal mucin as possible. ENBD is frequently obstructed by mucin and may be
      helpful only in selected cases.

PMID- 18609171
TI  - Autoimmune enteropathy in Swedish children, 1985-2002: a call for strict
      diagnostic criteria.
AB  - OBJECTIVE: To investigate the incidence, prevalence and the long-term outcome of
      autoimmune enteropathy in Sweden. MATERIAL AND METHODS: In 2002 a questionnaire
      was sent to all paediatric departments in Sweden asking them to report all known
      cases of this condition from the period 1985-2002. RESULTS: The response rate was
      92%. Five patients were reported and 3 were included in the study. Only one
      patient fulfilled all the diagnostic criteria and two were considered as possible
      cases of autoimmune enteropathy. The incidence was 0.06 to 0.12 x 10(-5) and the
      prevalence was 0.05 to 0.10 x 10(-5) for children aged 0-16 years. At the end of
      the study period all 3 patients were still alive. Two boys were receiving
      immunosuppressive treatment and one girl was in remission and functioning well on
      a gluten-free diet only. One of the patients had adrenalitis. This combination
      has not been reported previously in autoimmune enteropathy. CONCLUSIONS:
      Autoimmune enteropathy in its severe forms is a rare disease in Sweden. None of
      the patients reported died during the study period. Comparative studies are
      difficult as different diagnostic criteria are used to diagnose this disease.

PMID- 18609172
TI  - Comparison of the clinicopathologic features between flat and polypoid adenoma.
AB  - OBJECTIVE: Several reports have suggested that flat colorectal adenomas might
      exhibit a higher potential for malignancy compared to polypoid adenomas. Although
      the clinical importance of the shape of polyps is stressed, the controversy
      surrounding the malignant potential of flat adenomas continues. The aim of this
      study was to compare the clinicopathologic characteristics, including degree of
      dysplasia and malignancy, between flat and polypoid adenomas 5 mm in size or
      larger. MATERIAL AND METHODS: A total of 3263 polyps (254 flat adenomas and 3009
      polypoid adenomas), >/=5 mm in size, diagnosed in 1883 patients by colonoscopy
      were analyzed. RESULTS: Flat adenomas were found in 10% of patients, which
      represented 7.8% of all adenomas removed. The flat adenomas were larger in
      diameter than the polypoid adenomas (14.8+/-12.6 mm versus 8.6+/-5.0 mm, p
      <0.01), had a higher rate of villous components (18.5% versus 11.4%, p <0.01), a
      higher rate of high-grade dysplasia (9.4% versus 4.2%, p <0.01), and a higher
      rate of malignancy (10.2% versus 3.6%, p <0.01) than polypoid adenomas. However,
      there was no difference in the rate of high-grade dysplasia or carcinoma between
      flat and polypoid adenomas of equal size. It was shown by multivariate analysis
      that rectosigmoid location, larger size, and presence of a villous component were
      associated with a higher rate of malignancy, but not with flat morphology.
      CONCLUSIONS: Flat adenomas, which were of a relatively large size in this study,
      were not associated with a higher risk for high-grade dysplasia and carcinoma
      compared with polypoid adenomas.

PMID- 18609173
TI  - Clinical response to gluten withdrawal is not an indicator of coeliac disease.
AB  - OBJECTIVE: Although the diagnosis of coeliac disease requires specific
      histological and serological findings, patients considered to be affected by
      coeliac disease only on the basis of clinical improvement after gluten withdrawal
      are commonly referred to our outpatient clinic. The objective of this study was
      to investigate whether the clinical response of gastrointestinal symptoms to
      gluten withdrawal and subsequent dietary re-introduction could be an indicator of
      the presence of coeliac disease. MATERIAL AND METHODS: From December 1998 to
      January 2007, 180 patients on a gluten-free diet because of a diagnosis of
      coeliac disease not based on proper diagnostic criteria came to our out-patient
      clinic. In 112 of these patients, gluten was re-introduced into their diet.
      Subsequent duodenal biopsies and endomysial antibodies confirmed the diagnosis of
      coeliac disease in 51 of them. The relationship between improvement/worsening of
      symptoms and withdrawal/re-introduction of dietary gluten was analysed. RESULTS:
      Gastrointestinal symptoms improved in 64.7% of coeliac patients and 75.0% of non
      coeliac patients after gluten withdrawal (chi(2) test, p=NS). Gluten re
      introduction was followed by clinical exacerbation in 71.4% of coeliac patients
      and 54.2% of non-coeliac patients (chi(2) test, p=NS). The positive predictive
      value for clinical improvement after gluten withdrawal was 36%; the positive
      predictive value for clinical exacerbation after gluten re-introduction was 28%.
      CONCLUSIONS: Clinical response to either withdrawal or re-introduction of dietary
      gluten has no role in the diagnosis of coeliac disease.

PMID- 18609175
TI  - Serum adipokine levels in chronic liver diseases: association of resistin levels
      with fibrosis severity.
AB  - OBJECTIVE: Leptin and adiponectin have been implicated in the pathogenesis and
      progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C
      (CHC), but little is known about the role of resistin in chronic liver diseases.
      The objective of this study was to investigate serum levels of the above three
      adipokines in relation to the etiology of liver disease and to determine their
      associations with histological severity. MATERIAL AND METHODS: We prospectively
      evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70,
      NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological,
      anthropometric and laboratory data were recorded. Histological lesions were
      evaluated blindly according to the Ishak and the Brunt classifications for
      CHB/CHC and NASH, respectively. RESULTS: Serum adipokine levels were similar
      between CHB and CHC patients, while CHB/CHC patients had significantly lower
      leptin levels compared with NASH patients (8.3+/-7.3 versus 17.6+/-16.6 ng/ml,
      p=0.012) and higher adiponectin (10.2+/-5.1 versus 7.5+/-4 microg/ml, p=0.018)
      and resistin levels (7.1+/-2.5 versus 5.7+/-2.8 ng/ml, p=0.016). In CHB/CHC,
      there was no significant association between steatosis or necroinflammation and
      levels of adipokines, while the presence of moderate/severe fibrosis (stages 4-6)
      was associated with higher leptin and adiponectin levels in male but not in
      female patients and with lower resistin levels irrespective of gender or other
      factors (adjusted odds ratio=0.788, p=0.035). CONCLUSIONS: Serum adipokine levels
      depend on the etiology of liver disease differing between chronic viral hepatitis
      and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are
      independently associated with fibrosis severity, whereas in the association of
      leptin and adiponectin levels with fibrosis, it seems to be a gender effect.

PMID- 18609176
TI  - Impaired counter-regulation of interleukin-1 by the soluble IL-1 receptor type II
      in patients with chronic liver disease.
AB  - OBJECTIVE: To assess the production of the endogenous IL-1 modulators IL-1
      receptor antagonist (IL-1Ra), type I and II soluble IL-1 receptors (IL-1sRI and
      II) in patients with chronic liver disease (CLD). MATERIAL AND METHODS: Plasma
      levels of IL-1beta (IL-1beta) and IL-1 modulators were assessed in 126 CLD
      patients and 39 healthy controls. IL-1sRII was also measured in the supernatants
      of primary hepatocyte cultures. RESULTS: Plasma IL-1sRI and IL-1Ra levels were
      significantly higher in cirrhotic CLD patients than in non-cirrhotic CLD patients
      and in controls. Levels did not depend on the etiology of CLD. Likewise, plasma
      IL-1beta levels were elevated in CLD patients compared with those in controls. In
      contrast, IL-1sRII levels did not differ between CLD patients and controls.
      Cultures of human primary hepatocytes showed that IL-1sRII is induced by IL
      1beta, but not IL-6. CONCLUSIONS: In cirrhotic CLD patients elevated plasma IL
      1beta is not counteracted by endogenous levels of IL-1sRII, whereas high IL-1sRI
      is expected to neutralize the naturally occurring antagonist IL-1Ra, resulting in
      a dysregulation of the IL-1 system that might enhance pro-inflammatory activity
      of IL-1.

PMID- 18609178
TI  - Role of earlier gastroscopy in predicting findings on repeat gastroscopy in a
      population with a low H. pylori prevalence.
AB  - OBJECTIVE: Repeat gastroscopy is not recommended for patients without alarm
      symptoms and with a normal earlier gastroscopy. However, there is little
      information available on the consequences of this recommendation. The objective
      of this study was to examine the role of earlier gastroscopy results in
      predicting the findings at repeat gastroscopy. MATERIAL AND METHODS: Patients
      with previous gastroscopies presenting for a new gastroscopy during 2004-05 were
      included consecutively. A total of 293 patients who had undergone a gastroscopy a
      mean of 7.7 years (range 0.6-25.4 years) before the present gastroscopy were
      included in the study. The patients completed a questionnaire. The associations
      between the findings of the present gastroscopy and the findings of the previous
      gastroscopy and other patient characteristics were analysed by stepwise logistic
      regression. RESULTS: Nine percent of the patients were positive for Helicobacter
      pylori infection. An abnormal macroscopic finding, defined as any erosion, ulcer
      or other macroscopic finding with the exception of hiatus hernia, at the repeat
      gastroscopy was significantly positively associated with: 1) an abnormal finding
      at a previous gastroscopy (OR 2.94, 95% CI 1.48-5.85), 2) obesity (body mass
      index, BMI >30) (OR 2.89, 95% CI 1.28-6.55), 3) the presence of alarm symptoms
      (OR 2.68, 95% CI 1.29-5.56), and negatively associated with 4) the use of proton
      pump inhibitors (OR 0.48, 95% CI 0.24-0.98). The findings were not associated
      with age. CONCLUSIONS: Abnormal earlier gastroscopy findings, obesity and the
      presence of alarm symptoms were the strongest indicators of abnormal findings at
      repeat gastroscopy. Our results support a restrained gastroscopy policy in
      patients with no alarm symptoms and a normal earlier gastroscopy.

PMID- 18609180
TI  - Cure of Helicobacter pylori infection in all compliant patients:  report on 644
      subjects.

PMID- 18609183
TI  - Small-bowel adenocarcinoma in patient with Crohn's disease: report of a series of
      three cases.
AB  - Patients affected with Crohn's disease (CD) have a recognized, but low relative
      risk of developing small-bowel adenocarcinoma (SBA). In fact, SBA develops in
      2.2% of patients who have long-standing CD and it is seldom diagnosed
      preoperatively because of its rarity. A retrospective analysis of all cases of
      SBA in CD patients since 1980 was carried out in Rouen University Hospital. Three
      patients with known or unknown CD who presented with SBA with long-term follow-up
      were analysed. In our first case, the occlusive syndrome revealed SBA and CD
      simultaneously. Most ileal carcinomas in CD are located in strictures and are
      often incidentally diagnosed postoperatively, as in our three cases. Digestive
      surgeons and gastroenterologists must be aware that the diagnosis of SBA in CD is
      often made fortuitously on histological examination after surgical resection for
      an occlusive syndrome. Failure to detect SBA in patients with CD results in late
      diagnosis, with poor survival.

PMID- 18609184
TI  - Effects of treatment with glucagon-like peptide-2 on bone resorption in
      colectomized patients with distal ileostomy or jejunostomy and short-bowel
      syndrome.
AB  - OBJECTIVE: The gut hormone GLP-2 (glucagon-like peptide-2) seems to be involved
      in the circadian pattern of bone resorption, whereas parathyroid hormone (PTH) is
      an established key hormone in bone turnover. Endogenous GLP-2 secretion is
      lacking in colectomized patients with short-bowel syndrome (SBS) and they have
      reduced bone mineral density (BMD). The aim of the study was to investigate the
      anti-resorptive effect (assessed by s-CTX) of 14 days of GLP-2 treatment in these
      patients and to determine whether 56 days of treatment would improve BMD. PTH
      secretion in response to GLP-2 was also investigated in colectomized SBS patients
      and colectomized controls (with ileostomy). MATERIAL AND METHODS: Eight SBS
      patients and 13 patients with ileostomy were treated with subcutaneous injections
      of 1600 microg GLP-2 at bedtime for 56 and 14 consecutive days, respectively. BMD
      was determined at days 1 and 56 in SBS patients. On days 1 and 14, measurements
      of CTX, P1NP and PTH were taken 4 h after the GLP-2 injection. RESULTS: Patients
      with ileostomy showed a significant reduction in bone resorption after GLP-2
      injections at days 1 and 14. In contrast, there was no change in s-CTX after 1
      and 14 days in the SBS patients, and after 56 days of GLP-2 treatment there was
      no improvement in BMD. A significant reduction in PTH secretion in response to
      GLP-2 was observed only in patients with ileostomy. CONCLUSIONS: The decreased
      bone resorption in response to GLP-2 injections cannot be elicited in SBS
      patients and therefore precludes treatment of their osteopenia with GLP-2. The
      anti-resorptive response to GLP-2 seems to require an intact small intestine and
      may involve suppression of PTH secretion.

PMID- 18609187
TI  - Relationship between clinical parameters and the colitis-colorectal  cancer
      interval in a cohort of patients with colorectal cancer in  inflammatory bowel
      disease.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD) is associated with an increased risk
      of colorectal cancer (CRC), but more knowledge is needed about the possible
      relationship between clinical parameters and the time to development of cancer in
      IBD. The aim of the study was to determine the variability of the colitis-CRC
      interval and to analyze the association with clinical variables in an attempt to
      gain information on predictive factors of time to cancer within a relatively
      large cohort of CRC patients. MATERIAL AND METHODS: Patients diagnosed with IBD
      prior to 1 May 2005 at three university hospitals in Oslo were matched against
      the CRC files at the Cancer Registry of Norway. Only histological re-confirmed
      IBD and adenocarcinoma of the colorectum were included. RESULTS: Sixty-one
      patients with CRC in ulcerative colitis and 6 in Crohn's disease, including 13
      CRC in primary sclerosing cholangitis (PSC), covering a follow-up of 1625 patient
      years,were identified. The median time from diagnosis of IBD to CRC was 17 years.
      Seven of 58 patients (12%) developed CRC within 10 years from onset of IBD
      symptoms and 14/67 (21%) within 10 years after the diagnosis of IBD. The colitis
      CRC interval decreased by a factor of 0.154 (p = 0.018) when age at onset of IBD
      increased by one year. Mean age at onset of IBD was 30 years in patients with
      Dukes' stage C or D compared with 20 years in Dukes' stage A or B patients (p =
      0.017). The colitis-CRC interval decreased by a factor of 0.138 (p = 0.003) when
      the percentage of the colitis-CRC interval with active symptoms increased by 1%.
      Patients with PSC were significantly younger at onset of IBD symptoms (PSC: 19
      years versus no PSC:29 years, p = 0.04), but the colitis-CRC interval was similar
      to IBD without PSC (17 years versus 20 years, p = 0.236). Mean duration of the
      colitis-CRC interval was not related to family history or drug consumption prior
      to CRC. CONCLUSIONS: In the present cohort, for whom the median time from
      diagnosis of IBD to CRC was 17 years, 21% of the cancers developed before 10
      years of disease, which is before colonoscopic screening is usually recommended.
      High age at onset of IBD may be related to a more aggressive development of CRC
      in IBD and early inclusion in screening programs might be considered for this
      group of patients. Symptom activity but not the diagnosis of PSC, family history
      of CRC or IBD or drug treatment seems to have an effect on the colitis-CRC
      interval.

PMID- 18609189
TI  - Short-term moderate exercise programs reduce oxidative DNA damage as determined
      by high-performance liquid chromatography-electrospray ionization-mass
      spectrometry in patients with colorectal carcinoma following primary treatment.
AB  - OBJECTIVE: Oxidative DNA damage is believed to be involved in tumor formation and
      may be an important biomarker for malignant transition or relapse. A decrease of
      such damage has been observed in human and animal studies following dietary
      intervention and/or changes in lifestyle such as physical exercise at different
      levels of intensity. The purpose of this study was to carry out a clinical trial
      comparing the effects of a short-term (2 weeks) exercise program of moderate
      intensity (0.3-0.4 x maximal exercise capacity) (MI) versus high intensity (0.5
      0.6 x maximal exercise capacity) (HI) on individual urinary excretion of 8-oxo-dG
      before and after completion of the exercise programs. MATERIAL AND METHODS: In
      this short-term, prospective and randomized trial, 19 patients with colorectal
      cancer were allocated to the MI group following primary therapy and 29 to the HI
      group. Urinary 8-oxo-dG excretion concentration was determined by a highly
      sensitive detection method using high-performance liquid chromatography coupled
      to electrospray ionization mass spectrometry (HPLC-ESI-MS). Concentrations were
      determined immediately before and after completion of the exercise programs.
      RESULTS: Using HPLC-ESI-MS, it was shown that MI exercise significantly reduced
      urinary 8-oxo-dG excretion levels from 8.47 +/- 1.99 to 5.81 +/- 1.45 (ng/mg
      creatinine, mean +/- SE, p = 0.02), whereas HI exercise resulted in a non
      significant increase from 5.00 +/- 1.31 to 7.11 +/- 1.63 (ng/mg creatinine, p =
      0.18). Clinical characteristics (gender, age, body mass index (BMI), diet,
      chemotherapy/irradiation) were not associated/correlated with urinary 8-oxo-dG
      levels. CONCLUSIONS: By using HPLC-ESI-MS it was shown that short-term MI
      exercise after primary therapy in patients with colorectal cancer was associated
      with lower levels of urinary 8-oxo-dG, suggesting decreased oxidative DNA damage.
      In contrast, HI exercise tended to increase DNA damage. A prospective trial is
      now warranted to prove that reduced oxidative DNA damage lowers the risk of
      relapse of colorectal cancer in treated patients.

PMID- 18609190
TI  - Quality of life in short-bowel syndrome: impact of fatigue and gastrointestinal
      symptoms.
AB  - OBJECTIVE: Patients with short-bowel syndrome (SBS) have impaired health-related
      quality of life (QoL). However, comparisons of QoL data with the data on other
      chronic gastrointestinal diseases are not available. The aim of this study was to
      assess QoL in SBS patients compared with that in the general population and with
      patients with inflammatory bowel disease (IBD). The potential relation between
      fatigue and gastrointestinal symptoms and impaired QoL in these patients was also
      investigated. MATERIAL AND METHODS: Four validated questionnaires were used to
      measure aspects of QoL (SF-36), psychological distress (hospital anxiety and
      depression scale, HAD), fatigue (fatigue impact scale, FIS), and gastrointestinal
      symptoms (gastrointestinal symptom rating scale, GSRS) in 26/28 patients (93%)
      attending a SBS clinic (median age 62 years, 15 F/11 M) at a tertiary referral
      center. Persons from the general population (n=286) as well as patients with IBD
      (n=41) of similar age and gender distribution as the SBS group acted as controls.
      RESULTS: SBS patients had significantly lower SF-36 physical and mental component
      summaries than those in the general population as well as significantly lower SF
      36 physical (p<0.05) but not mental (p>0.05) component summaries compared with
      those of IBD patients. Fatigue and gastrointestinal symptoms were more severe in
      SBS patients than in IBD patients (p>0.05). The SF-36 physical component summary
      was independently related to the physical FIS dimension (beta=-0.4, p=0.004), the
      GSRS eating dysfunction dimension (beta=-0.31, p=0.025), and opiate use (beta=
      0.28, p=0.031), regardless of diagnosis (SBS or IBD). CONCLUSIONS: Patients with
      SBS show poor QoL compared with that in the general population and also
      impairment of mainly physical health compared with that in patients with IBD.
      Fatigue and gastrointestinal symptoms are more severe in patients with SBS, which
      has an impact on QoL.

PMID- 18609195
TI  - Evaluation of cervical computed tomography findings in oropharyngeal tularaemia.
AB  - Cervical contrast-enhanced computed tomography (CECT) was performed in 16 cases
      (5M, 11F) of oropharyngeal tularaemia, diagnosed at Zonguldak Karaelmas
      University, Turkey, between January 2004 and March 2006. All patients showed
      lymphadenopathy with contrast enhancement, 12 of them with peripheral contrast
      enhancement. Lymph node necrosis was found in 13 of the patients, abscess
      formation in 9 and cyst formation in 13. This appears to be the largest series of
      cervical CECT in oropharyngeal tularaemia reported to date. Tularaemia is a
      differential diagnosis of massive adenotonsillar enlargement and extensive
      necrotic cervical lymphadenopathy.

PMID- 18609196
TI  - Asymptomatic bacteriuria in the elderly: high prevalence and high turnover of
      strains.
AB  - Asymptomatic bacteriuria (ASB) was followed in repeated prevalence surveys in a
      cohort of non-institutionalized residents (n=330), aged>or=80 y. Urine samples
      were collected at baseline, and at 6, and at 18 months. Phenotyping (PhenePlate)
      was performed on isolates of Escherichia coli to evaluate strain relatedness. ASB
      occurred in 19.0, 19.4, and 19.9% in women, and in 9.4, 9.6 and 7.9% in men, at
      baseline and at the 6- and 18-months follow-up, respectively, and ASB was found
      at least once in 37% of women and in 20% of men. Of those with ASB at baseline,
      60% also had ASB in the 2 subsequent surveys. Among those with persisting E. coli
      bacteriuria, 76% and 40%, respectively, carried the same strain at the 6- and 18
      months follow-ups. In women, we found that the risk of developing a symptomatic
      urinary tract infection within 24 months was higher among those with ASB at
      baseline than in those without bacteriuria (p=0.019). ASB is common and often
      persistent, but we found a high turnover of strains, indicating a high rate of
      recolonization.

PMID- 18609198
TI  - Incidence of peritonsillar abscess and relationship to age and gender:
      retrospective study.
AB  - The incidence of peritonsillitis is not very well known. A retrospective study
      was performed at the Ear, Nose and Throat clinic (ENT) at the University Hospital
      of Orebro Sweden. We studied every case from 2002 to 2004 and related it to a
      well-defined catchment area of 179,200 inhabitants. We identified 283 events of
      peritonsillitis, of which 85 were defined as peritonsillar cellulitis (PTC).
      Peritonsillar abscess (PTA) was found in 198 events in patients between 7 and 82
      y of age. 13 patients had 2 episodes of PTA during the study period. The overall
      incidence was 37/100,000/y. The highest incidence was found between 14 and 21 y
      of age, with 124/100,000/y. The male: female ratio was 1: 1. Affected females
      were younger than males (p=0.04), and the peak incidence was earlier for females.
      This may be due to differences in immunological response, owing to hormonal
      maturation. The annual incidence of PTA was higher in this study than found in
      previous studies, which is probably attributable to the fact that our study
      identified almost all cases in the population.

PMID- 18609199
TI  - Dengue and liver disease.
AB  - Acute hepatitis and hepatic encephalopathy are rare manifestations of dengue
      haemorrhagic fever (DHF). We report 4 children aged 8 months to 3 y who presented
      with severe hepatic dysfunction. Three male infants had in addition hepatic
      encephalopathy and 2 of them succumbed to their disease suggesting that hepatitis
      with encephalopathy has a very high mortality.

PMID- 18609200
TI  - Suspected Crimean Congo Haemorrhagic Fever cases in Albania.
AB  - During 2003 to 2006 samples from 34 Albanian patients with suspected Crimean
      Congo Hemorrhagic Fever (CCHF) were tested by serology and PCR for CCHF virus;
      negative samples were further tested for hantaviruses, Leptospira spp. and
      Rickettsia spp. CCHF virus was detected in 38.2% of cases, hantaviruses in 11.7%,
      and leptospirosis and rickettsiosis were diagnosed in 29.4% and 2.9% of cases,
      respectively. There is a seasonal and clinical overlapping among the 4 diseases
      in Albania, suggesting that testing for these agents is necessary in cases with
      fever and haemorrhagic manifestations.

PMID- 18609201
TI  - Pericarditis as a presenting sign of infective endocarditis: two case reports and
      review of the literature.
AB  - Pericarditis as a presenting sign of infective endocarditis is rare. Here we
      describe 2 cases and an additional 19 cases of pericarditis as a presenting sign
      of infective endocarditis reported during the last 40 y. 71% of patients were
      young males (mean age 43.2 y). The most commonly reported underlying conditions
      were diabetes mellitus type 2 (5 patients, 24%), and substance or alcohol abuse
      (4 patients, 19%). The native aortic valve was the most frequently involved
      valve. The most common symptoms were fever, cough or dyspnoea, and chest pain.
      Overt tamponade was diagnosed in 47% of the patients. However, pulsus paradoxus
      and pericardial friction rub were rare. A heart murmur was heard in 12 patients
      (57%). Staphylococcus aureus was the most commonly isolated pathogen
      concomitantly from blood and pericardial fluid. 16 patients (76%) were operated.
      Six underwent a pericardial procedure, 5 underwent valve replacement, 4 both, and
      1 patient was operated for pseudoaneurysm. Mortality rates were 60% and 31% of
      patients treated with antibiotics alone versus antibiotics and surgical
      intervention, respectively. In patients presenting with pericarditis with or
      without cardiac tamponade, the possibility of infective endocarditis should be
      considered. Optimal therapy should consist of antibiotics and surgical
      intervention.

PMID- 18609197
TI  - Fungal infection as a risk factor for HIV disease progression among patients with
      a CD4 count above 200/microl in the era of cART.
AB  - The identification of clinical risk factors for AIDS in patients with preserved
      immune function is of significant interest. We examined whether patients with
      fungal infection (FI) and CD4 cell count >or=200/microl were at higher risk of
      disease progression in the era of cART. 11,009 EuroSIDA patients were followed
      from their first CD4 cell count >or=200/microl after 1 January 1997 until
      progression to any non-azoles/amphotericin B susceptible (AAS) AIDS disease, last
      visit or death. Initiation of antimycotic therapy (AMT) was used as a marker of
      FI and was modelled as a time-updated covariate using Poisson regression. After
      adjustment for current CD4 cell count, HIV-RNA, starting cART and diagnosis of
      AAS-AIDS, AMT was significantly associated with an increased incidence of non-AAS
      AIDS (IRR=1.55, 95% CI 1.17-2.06, p=0.0024). Despite low incidence of AIDS in the
      cART era, FI in patients with a CD4 cell count >or=200/microl is associated with
      a 55% higher risk of non-AAS-AIDS (95% confidence interval 1.17-2.06, p=0.0024).
      These data suggest that patients with FI are more immune compromized than would
      be expected from their CD4 cell count alone. FI can be used as a clinical marker
      for disease progression and indirect indicator for initiation/changing cART in
      settings where laboratory facilities are limited.

PMID- 18609202
TI  - Molecular epidemiology of the global and temporal diversity of Candida
      parapsilosis.
AB  - We examined the global epidemiology of C. parapsilosis and assessed the
      discriminatory capabilities of restriction fragment length polymorphism (RFLP)
      and RAPD typing methods. We used EcoRI digestion of cellular DNA to generate
      RFLP; RAPD analysis on genomic DNA. Band profiles were used to distinguish and
      group isolates. From 7 diverse geographic areas, 536 isolates obtained over 35 y
      were placed into 23 RFLP subgroups. Subtype VII-1 was dominant worldwide (82.4%
      of isolates). Dividing the isolates into VII-1 versus non-VII-1 showed temporal
      variation for the USA pre-1995 versus post-1995 (p<0.0001) and versus Europe pre
      1995 (p<0.0001). Genotype distribution differed among localities (p<0.0001);
      Mexico was unique (p<0.05) due to the high proportion of non-VII-1. The
      prevalence of C. parapsilosis RFLP type VII-1 apparently has risen in the USA and
      current isolates show some variation in distribution of types in some non-USA
      localities. There were no differences in distribution of types comparing babies
      versus adults, or bloodstream isolates versus colonizing or environmental
      isolates. RAPD typing showed 3 major profiles, but was less discriminatory.

PMID- 18609203
TI  - Molecular characterization of vancomycin-resistant Enterococcus spp. clinical
      isolates from Hungary and Serbia.
AB  - The objectives of this work were to collect and characterize vancomycin-resistant
      Enterococcus faecium (VREF) clinical isolates from Hungary and Serbia and to
      analyse their genetic relatedness. VREF isolates were initially typed by PFGE. A
      selection of VREF isolates representing all participating hospitals was further
      examined by multiple-locus variable-number tandem repeat analysis (MLVA) and
      multilocus sequence typing (MLST). VanB VREF isolates (n=18) recovered from
      blood, urine and faecal cultures at a Budapest hospital between August 2003 and
      December 2004 were molecularly characterized. Macrorestriction analysis of the
      isolates revealed their monoclonal relatedness. A cluster of infections caused by
      2 distinct VanA VREF clones recovered from 6 departments was identified in a
      Belgrade hospital in Serbia. The vanA resistance determinant was transferable by
      in vitro conjugation experiments. We also identified 2 vanA-positive E.
      gallinarum blood culture isolates in this Belgrade hospital. Molecular typing of
      representative VREF isolates from Hungary and Serbia by MLVA and MLST revealed
      that all tested isolates belonged to MLST complex CC17 and the corresponding MLVA
      cluster 1. Our results extend the documented occurrence of CC17 to a new region
      in Europe.

PMID- 18609205
TI  - Antiphospholipid antibodies investigation in Pneumocystis jirovecii carriers.
AB  - It is well documented that antiphospholipid antibodies are increased in patients
      with HIV-1 infection and these are most commonly seen in those with Pneumocystis
      jirovecii pneumonia. Therefore it has been proposed that this could be the cause
      of its presence. Recently, P. jirovecii subclinical infection has been described
      in non-immunodeficient patients. We report here our experience concerning the
      possible relationship between P. jirovecii infection in non-immunocompromized
      adults and the production of antiphospholipid antibodies. Circulating lupus
      anticoagulant and IgM anticardiolipin antibodies were negative in all patients.
      IgG anticardiolipin antibodies were positive in 2 out of 5 (40%) P. jirovecii
      carriers and 2 out of 10 (20%) subjects with no evidence of pulmonary infection
      by this microorganism (p=0.4).

PMID- 18609206
TI  - Seroprevalence of Bartonella henselae antibodies in blood donors in Crete.

PMID- 18609207
TI  - Broad-range PCR as a supplement to culture for detection of bacterial pathogens
      in patients with a clinically diagnosed spinal infection.
AB  - We aimed to evaluate broad-range PCR and subsequent sequencing compared to
      conventional culture in the diagnosis of spinal infection. The method was a
      prospective study of all patients admitted to Aarhus University Hospital for
      surgery during a 12-months period with a clinically diagnosed infection of the
      spine. Samples from patients undergoing surgery for non-infectious causes
      (malignancy etc.) were included as control group. Specimens were submitted to
      conventional culture and molecular investigation with 16S rRNA gene amplification
      and sequence analysis. 38 patients were included in the study (clinically
      diagnosed spinal infections=18; non-infectious diseases=20). The specificity was
      excellent for both culture and PCR (95% and 100%, respectively). A true culture
      positive result was obtained in 50% of patients (9/18) and 61% was positive
      (11/18) by broad-range PCR. When combined, culture and PCR allowed for a
      microbiological diagnosis in 72% of patients (13/18). A positive culture was
      found only in patients treated < or =7 d compared to < or =16 d for PCR. However,
      PCR and culture result were equally negatively affected by duration of treatment.
      The combination of culture and broad-range PCR substantially adds to the number
      of microbiological diagnoses obtained, and improves the clinician's opportunity
      to tailor therapy to individual patients.

PMID- 18609208
TI  - Short-term success, but long-term treatment failure with linezolid for
      enterococcal endocarditis.
AB  - We report a case of linezolid treatment failure for Enterococcus faecalis
      endocarditis. Despite success during and shortly after treatment, the patient had
      a relapse after 7 weeks. Due to prior anaphylactic reaction to penicillin,
      desensitization was performed, and successful penicillin therapy given. The
      efficacy of linezolid for enterococcal endocarditis remains questionable.

PMID- 18609214
TI  - Evaluation of PCR as rapid microbiological method in diagnosis of pneumococcal
      pneumonia.

PMID- 18609222
TI  - Occult hepatitis B in HIV-HCV coinfected patients.
AB  - The prevalence of occult hepatitis B infection in HIV infected patients is
      controversial, varying from less than 1% to 62% in different studies. Blood
      samples of 111 HIV-infected patients, HCV-positive, HBs antigen negative,
      followed in the APROCO-ANRS EP11 cohort, were used to detect HBV DNA by using 2
      different validated assays (Cobas Amplicor HBV Monitor Test and INSERM U271
      qualitative ultra-sensitive PCR), completed when positive by HBV real-time PCR.
      HBV DNA was found in 6 (5.4%, 95% CI 1.2%-9.6%) patients by at least 1 of these
      assays, but none tested positive in all 3 assays. All 6 patients had anti-HBc
      without anti-HBs antibodies; 5 were not on lamivudine. Their median CD4 and CD8
      counts were significantly lower and their HIV viral load higher than in the other
      105 patients. In conclusion, the prevalence of occult hepatitis B may vary
      significantly according to the molecular assay used, even though these assays are
      validated with high specificity and quite high sensitivity. Occult hepatitis B
      may be encountered in HIV-HCV coinfected patients without anti-HBV treatment,
      with anti-HBc but without anti-HBs antibodies, and relatively low immunity,
      suggesting a potential risk of further reactivation, as already sporadically
      reported.

PMID- 18609239
TI  - Men's experiences of giving and taking social support after their wife's spinal
      cord injury.
AB  - The aim of this study was to gain an understanding of how men living with women
      with spinal cord injury (SCI) experienced and acted when they were giving and
      taking social support to and from their wives and other persons in their social
      network. Another aim was to give some possible explanations of the complex
      process of change that they went through. Data were collected through in-depth
      interviews with four men and field notes. To describe the men's subjective
      experiences and the process of change, a narrative approach inspired by
      Polkinghorne was used. The analyses resulted in one story that included the four
      men's experiences and action. The story showed that when the men went through a
      process of change, they used and needed both emotional and practical support to
      handle their new life situation. Furthermore, the men's experiences and action
      against social support changed over time. This indicated that, through narratives
      from spouses, professionals within rehabilitation could understand the process of
      change they went through after their partner's sudden injury, and support them to
      find strategies to handle their changed life situation. To give some possible
      explanations for the men's experiences and action during the process of change,
      the findings are discussed in relation to theories concerning adaptation and
      coping.

PMID- 18609240
TI  - Occupational therapists' descriptions of their work with persons suffering from
      cognitive impairment following acquired brain injury.
AB  - The aim of the present study was to investigate how Swedish occupational
      therapists describe their work with persons suffering from cognitive impairment
      following acquired brain injury. A qualitative descriptive approach was used and
      interviews were conducted with 12 occupational therapists working in community
      and county council care. Qualitative content analysis was used and revealed three
      main themes: (1) "To make the invisible visible", (2) "To collaborate-a
      prerequisite for success", and (3) "Dilemmas to handle". The findings showed a
      complex scenario where the occupational therapists worked to make the cognitive
      impairments visible to themselves, the clients, and persons close to the client.
      Collaboration was perceived as a key factor. The dilemmas concerned different
      aspects in the rehabilitation process, which affected the occupational
      therapists' work with the clients. Identified areas in need of improvement are
      prioritizations and additional education regarding both intervention methods and
      theory. A reluctance to use standardized assessments was expressed and research
      that identifies and overcomes those hindrances in clinical practice is needed.
      Therapeutic use of self was described as important. To understand and illuminate
      the occupational therapists' comprehension of the concept further research is
      required.

PMID- 18609241
TI  - Supervision in occupational therapy regarding rehabilitation of elderly people in
      Sweden.
AB  - The aim of this study was to investigate occupational therapists' supervision of
      healthcare workers regarding rehabilitation of elderly people in Swedish
      municipal elderly care. Data were collected through a self-report questionnaire
      developed for this study. In total, 238 occupational therapists working with
      supervision of healthcare workers in the field of municipal elderly care
      participated in the study. Data were analysed using descriptive statistics. For
      supervising healthcare workers, the participants rated highly the importance of
      cooperation and communication. Many of the participants considered both the time
      available for one supervision session and the number of supervision sessions to
      be insufficient. The result also demonstrated that the participants supervised
      healthcare workers more frequently in P-ADL than in I-ADL. A majority of the
      participants supervised other groups of people in addition to healthcare workers.
      The lack of research work in supervision specific to occupational therapy
      indicates a need for more studies in this area.

PMID- 18609242
TI  - Factors that impede the discharge of long-term schizophrenic inpatients.
AB  - The aim of the present study was to explore factors that impede the discharge of
      long-term schizophrenic inpatients, and it was focused on the patients'
      subjective views. Semi-structured interviews based on the Occupational Self
      Assessment (OSA) of 73 long-term inpatients with schizophrenia and 24
      schizophrenic patients who had been discharged from hospitals after a long-term
      stay were conducted. Logistic regression analysis was performed. The results
      revealed that the factors that impeded the discharge of schizophrenic patients
      from hospitals were advanced age, severe mental symptoms, and higher rating of
      one's own capabilities in daily living. These results suggest that schizophrenic
      long-term inpatients require occupational interventions that help patients to
      have a realistic image of their daily life after discharge and that invite them
      to update their self-assessments of competence related to the skills needed for
      daily life.

PMID- 18609243
TI  - Experiences of ethical dilemmas in rehabilitation: Swedish occupational
      therapists' perspectives.
AB  - The aim of this study was to describe Swedish occupational therapists'
      experiences of encountering ethical dilemmas in rehabilitation and strategies
      they used to handle the situations. Twelve occupational therapists who work with
      adults with developmental disabilities were interviewed using a semi-structured
      interview design. Data were analysed using qualitative content analysis. The
      results showed that ethical dilemmas were common in the occupational therapists'
      daily work within rehabilitation. Many situations that created ethical dilemmas
      were related to occupational therapists who worked with clients and their
      relatives, and other healthcare providers. The results showed further that
      occupational therapists found it difficult to make decisions and to optimize
      clients' participation in decision-making, to set limits and act professionally,
      and to best handle the situation for the client and avoid ethical dilemmas. This
      study indicates the importance of illustrating experiences of ethical dilemmas
      within occupational therapy praxis and the meaning of discussing ethical dilemmas
      with different healthcare providers to reach a divided view of the client in
      order to develop successful and healthy strategies that will optimize the
      rehabilitation of clients with developmental disabilities.

PMID- 18609244
TI  - Awareness of driving disability in people with stroke tested in a simulator.
AB  - The aim of this study was to explore and describe awareness of driving disability
      in people with driving difficulties after stroke. The study comprised a
      consecutive sample of 38 participants with stroke who showed difficulties in a
      technically advanced, interactive driving simulator. Driving ability in the
      simulator was measured using Performance Analysis of Driving Ability (P-Drive).
      Awareness of driving disability was measured using a modified version of
      Assessment of Awareness of Disability (AAD), measuring the discrepancy between
      observed driving actions and self-reported disability after a driving evaluation
      in a simulator. A majority of the participants (n = 36) demonstrated driving
      ability that was below the cut-off criterion for P-Drive. Furthermore, a majority
      of the items measuring awareness of driving disability were scored low,
      indicating that participants with stroke who did not pass a driving evaluation
      also had limited awareness of driving disability. A General Linear Model analysis
      indicated that awareness of driving disability and cognitive screening outcome
      explained 74% of the variance in driving ability. This study indicated that a
      majority of the people with stroke who fail a driving evaluation also have
      limited awareness of their disability, which indicates the need to address
      awareness in driving evaluations.

PMID- 18609245
TI  - Relevance and focal view point in occupational therapists' documentation in
      patient case records.
AB  - The Code of ethics for occupational therapists stipulates how occupational
      therapists should think about the profession's central concepts in practice,
      where "Activity" and "Health" are two such concepts. Other guiding principles for
      practice are the Occupational Therapy Process Model and the ARTUR Case Record
      Structure. The aim of this study was to identify and describe how occupational
      therapists at a hospital in Sweden accomplished documentation of occupational
      therapy cases in patient case records. A stratified and random sample of one
      hundred occupational therapy cases was evaluated in relation to a checklist. The
      results showed that only 21% of the documented occupational therapy cases were
      complete. Often, the notes were found under the wrong keyword and 12% of the
      occupational therapy cases were indistinct and did not belong to any of the
      intervention categories in which occupational therapists normally intervene.
      Despite this, the majority of the documented occupational therapy cases reflected
      the ICF's Activity/Participation component. Our conclusion of this study is that
      even if not all of the occupational therapy cases documented in the patient
      records included all relevant information, the documentation still reflected a
      focus on "activity" and holistic health notions.

PMID- 18609248
TI  - Outcomes of activity-based assessment (BIA) compared with standard assessment in
      occupational therapy.
AB  - This study was aimed at investigating the outcomes of an activity-based
      assessment (BIA) compared with standard assessment (SA) for evaluating clients
      undergoing psychiatric occupational therapy. Patients admitted to a psychiatric
      occupational therapy unit were randomized into the BIA or the SA assessment. The
      outcome indicators were (a) clients' satisfaction with the occupational therapy
      during the assessment period, (b) clients' awareness of capacities and
      occupational problems, (c) satisfaction with the assessment among the referring
      physicians, and (d) outcomes of the intervention following the assessment, in
      terms of changes in occupational performance and satisfaction. The groups did not
      differ in awareness of occupational problems, but the BIA group was more
      satisfied than the SA group with the support of their contact person and with the
      group leader during the period of assessment. Furthermore, physicians receiving
      feedback on patients in the BIA group were more satisfied than those receiving
      feedback on patients in the SA group. However, the groups did not differ
      concerning change during the treatment period in occupational performance or
      satisfaction. Thus, there was no difference between the assessment methods
      regarding the outcomes of the treatment following assessment. Minor advantages
      from the patients' perspective were found, in terms of better satisfaction in the
      BIA group, and from the referring physicians' perspective the BIA clearly seemed
      more satisfying than the SA. Thus, the findings showed that the BIA possessed
      better qualities than the SA regarding the indicators pertaining to satisfaction,
      but not concerning awareness of capacities and problems or the outcome of the
      subsequent treatment.

PMID- 18609249
TI  - Do characteristics of practices and general practitioners influence the yield of
      diabetes screening in primary care? The ADDITION Netherlands study.
AB  - OBJECTIVE: To investigate whether the yield of population-based diabetes
      screening is influenced by characteristics of the general practitioner (GP) and
      the practice. DESIGN: Cross-sectional study. SETTING: Seventy-nine general
      practices in the south-western region of the Netherlands. SUBJECTS: From 2002 to
      2004, 56 978 people were screened for diabetes. GPs completed a questionnaire
      containing items on the GP (age, gender, employment, special interest in
      diabetes, providing insulin therapy) and the practice (setting, location, number
      of patients from ethnic minority groups, specific diabetes clinic, involvement of
      practice assistant, practice nurse or diabetes nurse in diabetes care). MAIN
      OUTCOME MEASURES: The ratio screen-detected diabetic patients/known diabetic
      patients per practice (SDM/KDM) and the number of detected diabetic patients per
      practice adjusted for practice size and age distribution (SDM per standardized
      practice). RESULTS: The yield of screening per practice varied widely. Higher age
      of the GP (regression coefficient 0.20; 95% confidence interval, CI 0.07-0.34),
      urban location (-4.60; 95% CI -6.41 to -2.78) and involvement of the practice
      assistant (2.27; 95% CI 0.49-4.06) were independently associated with SDM/KDM.
      Using the other outcome variable, results were similar. Additionally, cooperation
      with a diabetes nurse was associated with a lower yield. CONCLUSION: A lower
      yield of screening, reflecting a lower prevalence of undiagnosed diabetes, was
      found in practices of younger GPs and in urban practices. A lower yield was not
      associated with an appropriate practice organization regarding diabetes care nor
      with a specialty of the GP in diabetes. The wide variation in the yield of
      screening stresses the importance of a screening programme in each general
      practice.

PMID- 18609251
TI  - Stories about bodies: a narrative study on self-understanding and chronic pain.
AB  - OBJECTIVE: To explore experiences from a process of change for women with chronic
      pain. DESIGN, SETTING, AND SUBJECTS: A group-based treatment programme was
      intended to increase the awareness of how attitudes, habits and bodily practices
      are established, developed, and can be transformed, and thereby probably reduce
      pain. A single case story from this treatment programme is presented. A semi
      structured interview was conducted with all participants about their experiences
      after completion of the programme. All eight women reported that they had
      benefited from participation. From these interviews a single case was chosen to
      represent the study's findings. A narrative analysis was conducted, focusing this
      patient's story from a phenomenological understanding of the body. RESULTS: The
      patient's story illuminates how events and experiences can be connected, and how
      she interprets her contemporary situation in the light of previous experiences.
      In this way, she alters her understanding and develops a new approach to her
      situation. Her story demonstrated how symptoms can be understood as the result of
      stressful habits that the body has developed as a reaction to demands from the
      surroundings. CONCLUSIONS: Reflection on how the body functions may lead to a new
      realization of how phenomena are interconnected, thus making changes possible.

PMID- 18609250
TI  - Barriers to adherence to hypertension guidelines among GPs in southern Sweden: a
      survey.
AB  - OBJECTIVE: To evaluate barriers to adherence to hypertension guidelines among
      publicly employed general practitioners (GPs). DESIGN: Questionnaire-based survey
      distributed to GPs in 24 randomly selected primary care centres in the Region of
      Skane in southern Sweden. SUBJECTS: A total of 109 GPs received a self
      administered questionnaire and 90 of them responded. MAIN OUTCOME MEASURES: Use
      of risk assessment programmes. Reasons to postpone or abstain from
      pharmacological treatment for the management of hypertension. RESULTS: Reported
      managing of high blood pressure (BP) varied. In all, 53% (95% CI 42-64%) of the
      GPs used risk assessment programmes and nine out of 10 acknowledged blood
      pressure target levels. Only one in 10 did not inform the patients about these
      levels. The range for immediate initiating pharmacological treatment was a
      systolic BP 140-220 (median 170) mmHg and diastolic BP 90-110 (median 100) mmHg.
      One-third (32%; 95% CI 22-42%) of the GPs postponed or abstained from
      pharmacological treatment of hypertension due to a patient's advanced age. No
      statistically significant associations were observed between GPs' gender,
      professional experience (i.e. in terms of specialist family medicine and by
      number of years in practice), and specific reasons to postpone or abstain from
      pharmacological treatment of hypertension. CONCLUSION: These data suggest that
      GPs accept higher blood pressure levels than recommended in clinical guidelines.
      Old age of the patient seems to be an important barrier among GPs when
      considering pharmacological treatment for the management of hypertension.

PMID- 18609252
TI  - Did a health dialogue matter? Self-reported cardiovascular disease and diabetes
      11 years after health screening.
AB  - OBJECTIVE: To study the potential impact of health screening, with or without a
      motivational health dialogue, on the risk and morbidity of cardiovascular
      diseases (CVD) and diabetes (DM). DESIGN: Two cross-sectional studies with an
      interval of 11 years. SETTING: The community of Harnosand, Sweden. SUBJECTS: In
      the first study, 402 men born in 1934, 1944, or 1954 underwent health screening
      for CVD prevention in 1989. In the second study, 415 men (of the same ages)
      completed a questionnaire in 2000 (11 years later). MAIN OUTCOME MEASURES: Odds
      ratio (OR) for self-reported CVD and DM. RESULTS: The odds ratio of self-reported
      CVD and DM was more than doubled among participants in the health screening
      without a health dialogue (OR 2.5; 95% CI 0.8-7.4) and threefold for those not
      participating (OR 3.0; 95% CI 1.0-8.8) compared with those who reported
      participation in health screening that included a structured health dialogue.
      CONCLUSIONS: Health screening for the prevention of CVD and DM benefits from
      inclusion of a structured, motivational health dialogue.

PMID- 18609253
TI  - The additional value of routine electrocardiograms in cardiovascular risk
      management of older people.
AB  - OBJECTIVE: To evaluate whether routinely performed ECGs in older people from the
      general population have added value for cardiovascular risk management beyond the
      information that is already available from their medical records. DESIGN:
      Observational, prospective cohort study. SETTING: General population. SUBJECTS: A
      total of 566 participants aged 85 years (377 women, 189 men). METHODS: Lifelong
      history of cardiovascular disease was assessed through medical records obtained
      from general practitioners. Baseline ECGs were evaluated for prior myocardial
      infarction and atrial fibrillation. During a 5-year follow-up period, complete
      cardiovascular mortality and morbidity data were gathered. RESULTS: During 5
      years of follow-up, 262/566 (46%) participants died, of whom 102/262 (39%) died
      from cardiovascular disease. Participants with a history of cardiovascular
      disease at age 85 years (284/566, 50%) had an increased cardiovascular mortality
      (HR 2.7, 95% CI 1.8-4.1) and morbidity (HR (myocardial infarction) 2.1, 95% CI
      1.3-3.6; HR (stroke) 2.7, 95% CI 1.6-4.9) compared with those without such a
      history. Participants with major ECG abnormalities (102/566, 18%) had an
      increased cardiovascular mortality (HR 1.8, 95% CI 1.1-2.8), but no increase of
      cardiovascular morbidity compared with those without major ECG abnormalities. In
      both participants with and without a history of cardiovascular disease, the
      presence of major ECG abnormalities was not associated with increased
      cardiovascular mortality or morbidity. CONCLUSIONS: In older people from the
      general population, a history of cardiovascular disease is a strong predictor of
      cardiovascular mortality and morbidity. Although abnormal findings on routine
      ECGs predict cardiovascular mortality, they do not provide additional prognostic
      information beyond the information available from medical records. Therefore,
      when accurate medical records are available, programmatic ECG recording is not
      effective in older people.

PMID- 18609254
TI  - Metabolic syndrome is associated with self-perceived depression.
AB  - OBJECTIVE: To study the association between metabolic syndrome (MetS) and self
      perceived depression. DESIGN: A cross-sectional community-based study. SETTING:
      Semi-rural community of Lapinlahti in eastern Finland in 2005. SUBJECTS: A total
      of 416 subjects in eight adult birth cohorts (55%) with complete Beck Depression
      Inventory (BDI-21) questionnaire data. MAIN OUTCOME MEASURES: The values of the
      21 BDI items and the BDI-21 total score with a cut-off point of 14/15 were used
      to study the association between MetS and depression. National Cholesterol
      Education Programme (NCEP) 2005 criteria were used for MetS classification.
      RESULTS: The total BDI-21 score was significantly higher in the subjects with
      MetS than in the subjects without MetS (p=0.020). Men with MetS were
      significantly worse off than men without MetS in the BDI-21 items of irritability
      (p=0.008), work inhibition (p=0.008), fatigability (p=0.037), weight loss
      (p=0.045), and loss of libido (p=0.014), while women were only so on the item of
      loss of libido (p=0.007). In a logistic regression analysis using a BDI-21 cut
      off point of 14/15 adjusted for age, marital status, vocational education, and
      working status, significant association was retained between perceived depression
      and elevated blood glucose among men (OR=1.697) and large waist circumference
      among women (OR=1.066). CONCLUSION: Elevated plasma glucose in men and central
      obesity in women are associated with self-perceived depression. This co
      occurrence deserves attention in clinical practice.

PMID- 18609255
TI  - Should milk-specific IgE antibodies be measured in adults in primary care?
AB  - OBJECTIVE: To study the association of milk-IgE antibodies in serum to milk
      related gastrointestinal symptoms in adults in primary care. DESIGN: Open
      clinical study. SETTING: Five outpatient clinics in primary care in Southern
      Finland. SUBJECTS: A total of 756 subjects who reported milk-related
      gastrointestinal symptoms in primary care and as controls 101 subjects with no
      such symptoms. METHODS: IgE values for specific food antigens were measured
      (Pharmacia CAP System) in a total of 857 subjects. All food screen-positive
      samples (>0.35 IU/l) were analysed further for IgE for untreated skimmed milk
      (milk-IgE) and for boiled milk. Those found positive for milk-IgE were invited
      for an open milk challenge test. RESULTS: Some 5.4% (46/857) of all subjects had
      a positive IgE antibody screen for food antigens. Of those with a positive food
      screen, 28% (13/46) had milk-IgE antibodies comprising 1.5% of the total group
      screened. The prevalence of milk-IgE was not statistically different between
      those with milk-related symptoms and those with no such symptoms. IgE antibodies
      for boiled milk were rare. All specific IgE antibody levels were low. Bloating
      was the only observed symptom in milk challenge tests. CONCLUSION: IgE antibodies
      to cow's milk were relatively rare in the adult population and were not
      indicative of milk protein allergy. The observed IgE levels were low and did not
      correlate with subjective milk-related symptoms. The measurement of milk-specific
      IgE in adults should be discouraged in outpatient clinics.

PMID- 18609257
TI  - Characteristics of non-urgent patients. Cross-sectional study of emergency
      department and primary care patients.
AB  - OBJECTIVE: To describe characteristics of patients seeking medical attention for
      non-urgent conditions at an emergency department (ED) and patients who use non
      scheduled services in primary healthcare. DESIGN: Descriptive cross-sectional
      study. SETTING: Primary healthcare centres and an ED with the same catchment area
      in Stockholm, Sweden. PATIENTS: Non-scheduled primary care patients and non
      referred non-urgent ED patients within a defined catchment area investigated by
      structured face-to-face interviews in office hours during a nine-week period.
      MAIN OUTCOME MEASURES: Sociodemographic characteristics, chief complaints,
      previous healthcare use, perception of symptoms, and duration of symptoms before
      seeking care. RESULTS: Of 924 eligible patients, 736 (80%) agreed to participate,
      194 at the ED and 542 at nine corresponding primary care centres. The two groups
      shared demographic characteristics except gender. A majority (47%) of the
      patients at the primary care centres had respiratory symptoms, whereas most ED
      patients (52%) had digestive, musculoskeletal, or traumatic symptoms. Compared
      with primary care patients, a higher proportion (35%) of the ED patients had been
      hospitalized previously. ED patients were also more anxious about and disturbed
      by their symptoms and had had a shorter duration of symptoms. Both groups had
      previously used healthcare frequently. CONCLUSIONS: Symptoms, previous
      hospitalization and current perception of symptoms seemed to be the main factors
      discriminating between patients studied at the different sites. There were no
      substantial sociodemographic differences between the primary care centre patients
      and the ED patients.

PMID- 18609256
TI  - Secular trends in cardiovascular risk factors with a 36-year perspective:
      observations from 38- and 50-year-olds in the Population Study of Women in
      Gothenburg.
AB  - OBJECTIVES: To study secular trends in cardiovascular risk factors in four
      different cohorts of women examined in 1968-1969, 1980-1981, 1992-1993 and 2004
      2005. DESIGN: Comparison of four representative cohorts of 38- and 50-year-old
      women over a period of 36 years. SETTING: Gothenburg, Sweden with approximately
      450,000 inhabitants. SUBJECTS: Four representative samples of 38- and 50-year-old
      women were invited to free health examinations (participation rate 59-90%, n
      =1901). MAIN OUTCOME MEASURES: Body mass index (BMI), systolic and diastolic
      blood pressure (SBP, DBP), leisure time exercise, use of antihypertensive
      medication, smoking, levels of haemoglobin, b-glucose, s-cholesterol, s
      triglycerides and HDL-cholesterol. RESULTS: There was no significant difference
      in mean BMI from 1968-1969 versus 2004-2005. Mean leisure time exercise was
      significantly higher in later born cohorts; in 1968, around 15% were physically
      active compared with 40% in 2004. SBP and DBP, mean s-cholesterol and s
      triglyceride levels were significantly lower in both 38- and 50-year-old cohorts
      in 2004-2005 versus 1968-1969. HDL-cholesterol (not measured until 1992-1993),
      showed a significantly higher mean level in 2004-2005. Reduction of risk factors
      was apparent in women with a high as well as low level of physical activity.
      Smoking declined most in women with high levels of physical activity.
      CONCLUSIONS: Several cardiovascular risk factors related to lifestyle have
      improved in middle-aged women from the 1960s until today. Most of the positive
      trends are observed in women with both low and high physical activity.

PMID- 18609258
TI  - Molecular analysis of MEFV gene mutations among Palestinian patients with
      Behcet's disease.
AB  - OBJECTIVES: The aim of our study was to determine the prevalence of Mediterranean
      fever gene (MEFV) mutations among Palestinian patients with Behcet's disease
      (BD). METHODS: We screened 42 BD patients from the West Bank and Jerusalem for
      most of the MEFV mutations known to date. Patients diagnosed clinically according
      to the International Study Group (ISG) criteria were recruited from Makassed
      Islamic Charitable Hospital and private clinics. We performed the DNA testing
      using direct DNA sequencing of exon 10 of the MEFV gene and using the
      amplification refractory mutation system (ARMS) technique for mutations located
      in other exons. RESULTS: We found that 40.5% of the samples had nine different
      MEFV mutations and one polymorphism. E148Q was the most prevalent mutation, found
      in 38.1% of the mutated alleles. M694V, V726A, M694I, A744S, P369S, R408Q, and
      F479L were each detected in 4.8% of the mutated alleles studied. The polymorphism
      P706 was detected in 9.5% of the mutated alleles. The mutations A744S, P369S,
      R408Q, and F479L were reported for the first time in BD patients. V722M, a novel
      MEFV mutation that has not been reported before in either FMF or BD patients, was
      identified in this study. CONCLUSION: This study is the first genetic analysis of
      MEFV mutations among Palestinian BD patients. It reflects their mutations
      profile, providing further data that MEFV mutations are an additional genetic
      susceptibility factor in BD.

PMID- 18609259
TI  - Stability of the upper neck during isometric neck exercises in rheumatoid
      arthritis patients with atlantoaxial disorders.
AB  - OBJECTIVE: To study the effect of isometric neck strength exercises on upper
      cervical stability in patients with rheumatoid arthritis (RA). METHODS: Twenty
      patients with a mean (SD) age of 58 (9) years and duration of RA of 27 (10) years
      volunteered for the study. Lateral radiographs of the cervical spine were taken
      to measure the current atlantoaxial distance (AAD) in flexion and extension.
      Maximal isometric neck flexion and extension strength values were measured by a
      dynamometer. Thereafter, AADs were measured from radiographs taken at 80-90%
      resistance of maximal strength. RESULTS: According to the full flexion
      radiographs at baseline, the patients were classified into three groups: eight
      patients without anterior atlantoaxial subluxation (aAAS) [AAD = 2.1 (2-3) mm],
      seven with unstable aAAS [AAD = 6.6 (5-8) mm], and five with stable aAAS [AAD =
      5.5 (5-7) mm]. During resisted flexion the AAD decreased by 5 (3-7) mm (p<0.001)
      in the unstable aAAS group, while in the other two groups the changes were minor.
      During resisted extension the AAD increased by 3 (2-6) mm (p<0.001) in the cases
      with unstable aAAS only. CONCLUSION: Isometric exercising towards flexion
      decreases the AAD in cases with unstable aAAS. Submaximal loading of the neck
      extensors by pushing the back of the head against the resistance even in the
      neutral position of the cervical spine leads to a decrease in the width of the
      cervical spine canal and is not recommended in unstable aAAS.

PMID- 18609260
TI  - Differences between rheumatology attending physicians and training residents in
      the management of rheumatoid arthritis in Spain.
AB  - OBJECTIVE: To evaluate the variability in the characteristics and management of
      rheumatoid arthritis (RA) patients between rheumatology attending physicians and
      training residents in Spain. METHODS: A retrospective medical record (MR) review
      was performed in a probabilistic sample of 1379 RA patients from 46 centres
      distributed in 16 of the 19 autonomous communities (AC) of Spain. RA patients'
      sociodemographic and clinical characteristics, healthcare resources use, and
      their single responsible physician's (defined as an identifiable single physician
      who attended the patient in more than 75% of visits) characteristics were
      recorded following a standardized protocol. Multivariate analyses were performed
      to assess differences in the characteristics and management of RA patients
      between attending physicians and training residents. RESULTS: A total of 1205 RA
      patients had a single responsible physician and were analysed (nearly 75% women
      with rheumatoid factor positive and more than 25% with persistent active
      disease), 49 of whom were followed by training residents and 1156 by attending
      physicians. In the multivariate analyses, irrespective of patient and disease
      characteristics, training residents' patients reported more hospital admissions,
      laboratory tests, and imaging techniques compared to attending physicians.
      Training residents also less frequently used combined therapy with disease
      modifying antirheumatic drugs (DMARDs). CONCLUSION: Training residents and
      attending physicians differ in RA patients' care. More efforts in training
      programmes are necessary to guarantee proper RA management and to improve the
      profile of the future rheumatologists.

PMID- 18609261
TI  - Hypogonadism in Wegener's granulomatosis.
AB  - OBJECTIVE: Current developments in the management of Wegener's granulomatosis
      (WG) focus on adoption of therapeutic strategies to avoid complications of both
      the disease and its therapy. Systematic analyses with respect to the reproductive
      system in WG are missing. METHODS: Data of a cross-sectional study of sexual
      hormones in 19 male WG patients were analysed. Disease extension was classified
      according to the ears, nose, and throat (E), lungs (L), and kidneys (K)
      classification (ELK classification) and to the disease extent index (DEI).
      Laboratory investigation included measurement of gonadotrophins, oestradiol, and
      total serum testosterone. Hypogonadism was defined by an increase in follicle
      stimulating hormone (FSH) beyond twice the upper reference range in the presence
      of low serum testosterone. Thirty-eight age-matched men served as controls.
      RESULTS: Hypogonadism was found in 52.6% of the patients but was not detectable
      in any of the controls (p<0.0001). No significant correlation to any clinical
      factor of systemic vasculitis, current or past medication was detected. In
      particular, testosterone or FSH levels were not correlated with current or
      cumulative use of cyclophosphamide or corticosteroids (p = 0.417, p = 0.293; p =
      0.893, p = 0.317). CONCLUSION: Data of our study revealed an unexpected high rate
      of hypogonadism irrespective of cyclophosphamide use, and subclinical involvement
      of the testes by the vasculitis itself might be an alternative explanation.
      Screening during the course of the disease is reasonable as hypogonadism might
      severely affect patients' quality of life. Further prospective studies with
      respect to gender-specific changes in the reproductive system are warranted.

PMID- 18609262
TI  - Good response to IL-1beta blockade by anakinra in a 23-year-old CINCA/NOMID
      patient without mutations in the CIAS1 gene. Cytokine profiles and functional
      studies.
AB  - Chronic infantile neurological cutaneous and articular (CINCA) syndrome is an
      autoinflammatory disease, defined by the triad of urticarial rash, neurological
      manifestations, and arthropathy, accompanied by recurrent fevers and systemic
      inflammation. Increasing neurological deficits result from aseptic meningitis.
      Sensorineural hearing loss and progressive loss of vision caused by
      keratoconjunctivitis or papilloedema may emerge. An autosomal-dominant
      inheritance is suspected although sporadic cases are reported frequently. Sixty
      per cent of CINCA patients carry mutations in the cold-induced autoinflammatory
      syndrome (CIAS1) gene. We report the favourable response of a 23-year-old CINCA
      patient without CIAS1 mutations to treatment with the recombinant interleukin-1
      (IL-1) receptor antagonist anakinra.

PMID- 18609263
TI  - A case of Evans syndrome combined with systemic lupus erythematosus successfully
      treated with rituximab.
AB  - Evans syndrome is a rare autoimmune disorder with unknown aetiology. Although
      corticosteroids and/or intravenous immunoglobulin (IVIG) are commonly used in its
      treatment, no standard strategy has been established. We report here a 44-year
      old male with refractory Evans syndrome combined with systemic lupus
      erythematosus (SLE) who responded well to rituximab. He was admitted to our
      hospital with severe bleeding caused by worsening of Evans syndrome. Despite
      treatment with a high-dose corticosteroid and IVIG, his thrombocytopaenia and
      haemolytic anaemia did not improve. We started rituximab at a dose of 375 mg/m(2)
      once a week for a total of two doses. There was significant improvement in his
      thrombocytopaenia and anaemia 1 month after administration of rituximab. Although
      the total immunoglobulin G (IgG) level did not change, the titres of platelet
      associated IgG (PA-IgG) and of an indirect antiglobulin test (IAT) decreased
      under the treatment with rituximab. It is suggested that rituximab would be a
      powerful candidate in the treatment of refractory Evans syndrome by depleting
      abnormal clone-producing autoantibody.

PMID- 18609264
TI  - The relationship between anti-cyclic citrullinated peptide and bone mineral
      density and radiographic damage in patients with rheumatoid arthritis.
AB  - OBJECTIVES: We aimed to investigate the relationship between anti-cyclic
      citrullinated peptide (anti-CCP) levels and bone mineral density (BMD), bone
      turnover, and radiographic damage in patients with rheumatoid arthritis (RA).
      METHODS: Eighty patients (68 females, 12 males, mean age 46.50+/-14.59 years)
      with RA were included in the study. Anti-CCP antibodies were measured by enzyme
      linked immunosorbent assay (ELISA). Bone turnover was studied by analysing serum
      levels of C-terminal telopeptide of type I collagen (sCTX, ng/mL), using an
      enzyme immunoassay. BMD was measured by dual-energy X-ray absorptiometry (DXA).
      Disease activity was assessed according to the Disease Activity Score that
      includes 28 joint counts (DAS28). Functional capacity was assessed by the Health
      Assessment Questionnaire (HAQ). RESULTS: Anti-CCP-positive patients were defined
      as group 1 and anti-CCP-negative patients as group 2. The mean disease duration
      was 7.53+/-6.27 years in group 1 and 6.25+/-6.51 years in group 2. Anti-CCP had a
      limited negative correlation with lumbar BMD (r = -0.220, p = 0.050) and a
      negative correlation with femoral BMD (r = -0.242, p = 0.031). There was no
      statistically significant correlation between anti-CCP and sCTX values (r =
      0.117, p = 0.301). Sharp scores were significantly higher in anti-CCP-positive
      than anti-CCP-negative patients (p = 0.012), and anti-CCP levels were
      significantly correlated with Sharp scores (r = 0.240, p = 0.032). CONCLUSIONS:
      We found that RA patients with higher levels of anti-CCP antibody had lower
      lumbar and femoral BMD. Anti-CCP levels were also associated with radiographic
      damage. Therefore, we suggest that anti-CCP may be a determinant of bone loss in
      patients with RA.

PMID- 18609266
TI  - Risk factors for local recurrence in patients with pTa/pT1 urinary bladder
      cancer.
AB  - OBJECTIVE: This study evaluated risk factors for local tumour recurrence, defined
      as recurrence at the same location in the bladder within 18 months after primary
      resection in patients with newly diagnosed pTa or pT1 bladder cancer. PATIENTS
      AND METHODS: The study included 472 patients with newly diagnosed pTa/T1 bladder
      cancer between 1992 and 2001. The patients were followed prospectively in
      accordance with a control programme and possible risk factors for tumour
      recurrence were registered. RESULTS: Local tumour recurrence was observed in 164
      (35%) patients, another 117 (25%) patients had recurrence at other locations in
      the bladder (non-local recurrence) and 191 (40%) had no recurrence at all. Tumour
      size and multiple tumours were significantly associated with a higher risk for
      developing local recurrence as opposed to non-local recurrence. Tumour category
      was of borderline statistical significance. Gender and tumour grade were not
      found to be risk factors for developing local recurrence. CONCLUSION: Tumour size
      and multiplicity are risk factors for development of recurrence at the same
      location in the bladder as the primary tumour. Local tumour recurrence may be a
      result of non-radical primary transurethral resection. One may consider
      recommending standard re-resection within 6-8 weeks in patients with tumours > 3
      cm or those with multiple primary tumours.

PMID- 18609267
TI  - Treatment outcome of day-time urinary incontinence in children.
AB  - OBJECTIVE: To analyse retrospectively the efficacy of day-time incontinence
      treatment in a secondary referral centre and consider characteristics of
      responders to the different therapeutic interventions. MATERIAL AND METHODS: All
      children treated for day-time urinary incontinence at the authors' clinics from
      2000 to 2004 were included. Children with ongoing urinary tract infections were
      excluded. Before treatment, children filled out registrations of incontinence
      episodes and 48h frequency-volume charts. Faecal disorders were treated before
      urinary incontinence. All children were subjected to standard urotherapy and were
      secondarily recommended a timer-watch. If standard urotherapy had no effect,
      anticholinergics were added. RESULTS: The study included 240 children with day
      time urinary incontinence. Of these, 45 had faecal problems and 17% obtained
      urinary continence when these were successfully treated. In total, 126 (55%)
      became dry on standard urotherapy. Of the 60 children who had a timer-watch in
      addition to standard urotherapy, 70% became dry. Of the 62 children who had
      anticholinergics in addition to standard urotherapy, 81% became continent.
      Fifteen (6%) did not achieve continence and another 11 patients were lost to
      follow-up. Children who became dry solely on standard urotherapy had a
      significantly lower voiding frequency (p<0.05), larger voided volumes as a
      percentage of those expected for age (p<0.01) and fewer incontinence episodes per
      week (p<0.05) than children needing anticholinergics. CONCLUSIONS: Most children
      achieve day-time continence solely on standard urotherapy. Children who need
      anticholinergics to achieve dryness seem to be those with more severe bladder
      reservoir function abnormalities and symptoms.

PMID- 18609268
TI  - Increased concentration of neutrophil elastase in urine from patients with
      interstitial cystitis.
AB  - OBJECTIVE: To identify proteins associated with interstitial cystitis (IC),
      protein profiles were analyzed using a proteomics-based approach. The study
      tested whether neutrophil elastase in urine correlates with the symptomatic
      condition of IC. MATERIAL AND METHODS: Proteins in urine from IC patients and
      healthy subjects were analyzed through a comparative proteomics approach using
      two-dimensional difference in-gel electrophoresis and nano-liquid chromatography
      tandem mass spectrometry. Neutrophil elastase activity was measured by the
      digestion of peptide substrate. RESULTS: The urinary neutrophil elastase
      concentration was significantly higher in IC patients with pain than in healthy
      subjects. It was significantly increased in patients with small bladder capacity
      (median 6.31 ng/ml in IC with a bladder capacity < 200 ml vs 1.15 ng/ml in IC
      with a bladder capacity > or = 200 ml and 0.18 ng/ml in healthy bladders, p <
      0.01). The concentration of neutrophil elastase did not correlate with the
      neutrophil count in the urine of IC patients. CONCLUSION: The concentration of
      neutrophil elastase increased in the urine of the IC patient subset with bladder
      pain and small bladder capacity.

PMID- 18609269
TI  - Extracorporeal magnetic innervation therapy: assessment of clinical efficacy in
      relation to urodynamic parameters.
AB  - OBJECTIVE: Clinical efficacy and urodynamic changes in women treated by
      extracorporeal magnetic innervation therapy (ExMI) were studied. MATERIAL AND
      METHODS: Women, presenting with urge, stress and mixed urinary incontinence, were
      included in a prospective study. ExMI was applied by an electromagnetic chair. To
      document clinical efficacy, a voiding diary and visual analogue scale were
      completed before and after treatment, together with a pad test. Detrusor
      overactivity (DO) and urethral instability (URI) were urodynamically documented.
      Clinical success was defined as more than 50% improvement in symptoms. RESULTS:
      Sixteen patients were included. At baseline, DO was observed in 10 patients, and
      URI in 12 patients. DO did disappear at follow-up in 60%, and a decrease in URI
      was seen in 66%. No significant clinical improvement was seen at follow-up.
      CONCLUSION: Although significant changes in urodynamic variables were observed,
      no significant improvement in clinical efficacy was seen after ExMI.

PMID- 18609270
TI  - Long-term follow-up of enuretic alarm treatment in enuresis nocturna.
AB  - OBJECTIVE: To evaluate the long-term success of the enuretic alarm device in
      patients with monosymptomatic primary nocturnal enuresis. MATERIAL AND METHODS:
      Sixty-two patients who had significant monosymptomatic primary nocturnal enuresis
      were included. They used an enuretic alarm for 3 months. At the end of the
      treatment, 15 of the patients did not have benefit from the enuretic alarm.
      Overall, 47 patients benefited from the enuretic alarm. The long-term follow-up
      was conducted prospectively. RESULTS: The mean age was 9.3 (range 5-16) years and
      mean follow-up time was 19.2 (range 12-30) months. In the follow-up period,
      relapse was observed in 46.8% (n = 22/47) of these patients. Twenty-two patients
      reused the enuretic alarm device for 3 months after relapse occurrence and 13
      patients (59%) recovered. Although re-relapse was observed in seven of them in
      the 6 months, six patients had a full response. In total, 65.9% of the patients
      (n = 31/47) maintained a full response after enuretic alarm treatment in the long
      term follow-up. Thirty-one of the 62 patients underwent combination treatment
      (enuretic alarm plus medical therapy) for unsuccessful enuretic alarm treatment.
      The overall full response rate for combination treatment was 16.1%. CONCLUSION:
      In the long-term follow-up, the enuretic alarm device provided an acceptable full
      response rate in patients with primary nocturnal enuresis.

PMID- 18609271
TI  - Atypical stromal hyperplasia of the prostate.
AB  - This paper reports a case of atypical stromal hyperplasia (ASH) of the prostate,
      i.e. a proliferation of stromal cells with scattered atypical nuclei, growing
      between benign prostatic glands. This is a rare lesion, but at least 36 cases
      have been reported. Although most ASHs arise in the transition zone in
      conjunction with benign prostatic hyperplasia, the current lesion was found in
      the peripheral zone of a 58-year-old man who underwent radical prostatectomy
      because of prostatic adenocarcinoma. The clinical impact of ASH is discussed and
      the literature reviewed.

PMID- 18609275
TI  - Effect of correcting serum cholesterol levels on erectile function in patients
      with vasculogenic erectile dysfunction.
AB  - OBJECTIVE: This study evaluated the effect of correction of serum cholesterol
      levels on erectile function and sildenafil treatment in patients with erectile
      dysfunction who have only hypercholesterolaemia as a risk factor for erectile
      dysfunction. MATERIAL AND METHODS: Twenty-five patients with a single risk factor
      (hypercholesterolaemia, serum cholesterol > 200 mg/dl) for erectile dysfunction
      were included in the study. The patients were recommended to take sildenafil
      (minimum two 100 mg tablets/week) 1 h before sexual intercourse for 4 weeks.
      After 1 month washout period, the patients received a single dose of atorvastatin
      10 mg/day for 1 month. Similarly, after a 1 month washout period, atorvastatin 10
      mg/day and sildenafil (minimum two 100 mg tablets/week) were administered for 1
      month as combination therapy. Erectile function was evaluated before and after
      all treatment regimens using the International Index of Erectile Function (IIEF).
      RESULTS: Following each treatment modality mean IIEF scores were significantly
      higher than baseline IIEF scores (p < 0.01). The IIEF score after sildenafil
      treatment was significantly higher than in the atorvastatin treatment group (p <
      0.01); and the IIEF score after combined treatment was significantly higher than
      in the sildenafil and atorvastatin treatment groups. CONCLUSIONS: Correction of
      serum cholesterol levels with atorvastatin could improve erectile function in
      patients who have only hypercholesterolaemia as a risk factor for erectile
      dysfunction. Furthermore, atorvastatin could improve sildenafil's effects on
      erectile function in hypercholesterolaemic patients with erectile dysfunction.

PMID- 18609277
TI  - Percutaneous cryoablation of small kidney tumours under magnetic resonance
      imaging guidance: medium-term follow-up.
AB  - OBJECTIVE: Minimally invasive treatment of small kidney tumours remains a
      challenge. Cryoablation has recently been advocated for such neoplasias. However,
      few series evaluating this therapeutic regimen are as yet available. The goal of
      this retrospective study was to evaluate the initial clinical experience of
      magnetic resonance imaging (MRI)-guided percutaneous cryotherapy of small renal
      tumours. MATERIAL AND METHODS: Seven patients with small renal tumours [mean
      diameter 21 (11-30) mm] underwent percutaneous renal tumour cryoablation using
      the Cryo-Hit delivery system. The procedure was performed in an MRI
      interventional unit, using a 0.23 Tesla open MRI imaging system. Five men and two
      women were included in the group. The average age was 61.5 (34-84) years. The
      patients had a solitary kidney (n = 2), renal insufficiency (n = 4) or a kidney
      graft (n = 1). The intervention was performed under general anaesthesia. Average
      time for the whole procedure was 235 min with 26 min of effective treatment time.
      Mean follow-up was 28 (7-43) months. RESULTS: All tumours were successfully
      ablated. There were no perioperative complications. Mean hospital stay was 2.4 (2
      5) days. One patient stayed for 5 days because therapeutic anticoagulation had to
      be reinitiated. No significant change in the perioperative value of the serum
      creatinine was noticed. No radiographic evidence of disease recurrence or new
      tumour development was identified during the follow-up. CONCLUSIONS: In this
      small group of patients, percutaneous renal tumour cryoablation under MRI
      guidance was efficient and carried no morbidity. Hospital stay was remarkably
      shorter than that of surgically treated patients. At medium-term follow-up, no
      recurrence has been identified, but long-term follow-up is required.

PMID- 18609278
TI  - Increasing numbers of ureteric injuries after the introduction of laparoscopic
      surgery.
AB  - OBJECTIVE: There is an impression that ureteric injuries have become more common
      during the past decade, and therefore this study aimed to determine the
      incidence, aetiology, features, treatment and outcomes of ureteric injuries over
      an extended period. MATERIAL AND METHODS: Records of patients treated for
      ureteric injury in 1986--2006, divided into three 7-year periods, were reviewed
      retrospectively. The numbers of open and laparoscopic gynaecological, surgical
      and endourological operations were ascertained. RESULTS: All 72 ureteric injuries
      recorded were iatrogenic, being diagnosed in 60 females and 11 males (mean age 52
      years). Only five injuries occurred during the first 7-year period (1986--1992),
      but the incidence was markedly higher during the following two 7-year periods, 28
      (1993--1999) and 39 (2000--2006), respectively. The injuries were mostly
      secondary to gynaecological procedures (64%) or general surgery (25%). Only 11%
      occurred in association with a urological procedure. The cause was mostly
      laparoscopic (56%) or open surgery (33%), and the injury was in most cases
      located in the lower ureter (89%). The diagnosis was usually delayed (in 79%),
      with a median time to diagnosis of 6 days. The injuries were managed by
      ureteroneocystostomy (49%), a ureteral stent (19%) or end-to-end anastomosis
      (12%). The complication rate was 36%. CONCLUSIONS: Iatrogenic ureteric injuries
      have increased markedly during the past two decades. Gynaecological laparoscopic
      procedures account for more than half of the injuries, and the most common
      location is the lower ureter. Most injuries are treated by ureteroneocystostomy,
      but endourological treatment yields acceptable results. To improve the management
      of ureteric injury there must be a high index of suspicion, especially during
      laparoscopic operations.

PMID- 18609281
TI  - Evaluation of a non-invasive bladder volume measurement in children.
AB  - OBJECTIVE: Postoperative urinary retention (PUR) is associated with
      overdistension of the bladder. The prevention of PUR by routine catheterization
      may increase the risk of urinary tract infection. Postoperative monitoring of the
      bladder volume by ultrasound to prevent PUR is reliable in adults, but has not
      been evaluated in children. MATERIAL AND METHODS: The BladderScan BVI 6200, an
      ultrasound device specifically designed for children, was assessed. Forty
      patients who required urinary catheter placement during surgery or during
      intensive care unit stay were entered into this blinded calibration study. An
      assessment of bladder urine volume by ultrasound was performed before and after
      catheterization in surgical patients. In these patients and intensive care
      patients 0, 2.5 or 5 ml/kg sterile normal NaCl was injected through the bladder
      catheter and the catheter was clamped. Volumes estimated with ultrasound were
      compared with measured catheter drainage or/and injected volume after the scan.
      RESULTS: The mean relative difference (bias) between the ultrasound estimate and
      the injected volume was -20% (95% confidence interval 140 to -180%). Precision,
      estimated using the Wilcoxon signed ranks test, showed a significant difference
      (Z = -3.25, p = 0.001) between the ultrasound-estimated volumes and the injected
      volumes. CONCLUSIONS: This study could not confirm good agreement between the
      ultrasound-estimated volumes and the injected volumes at volumes below 5 ml/kg.
      Bladder volumes were underestimated with a very broad 95% confidence interval.
      The ultrasound device should not replace current clinical assessment.

PMID- 18609284
TI  - Sexual function in patients with end-stage renal disease.
AB  - OBJECTIVE: Patients with chronic renal disease have sexual dysfunction to a great
      degree, but not many studies have been performed to study desire and sexual
      function in both men and women and the effects of active treatment for end-stage
      renal disease (ESRD). The aim of this study was to compare sexual function in
      patients with and without treatment for ESRD, where the patients served as their
      own controls. MATERIAL AND METHODS: Sexual function was investigated in 117
      patients with ESRD using a questionnaire in which the patients compared their
      sexual function before and after the onset of renal disease. RESULTS: An overall
      decrease was seen in sexual desire (46%) and initiative (68%), and a pronounced
      decrease in sexual function, with regard to erection/lubrication (68%) and
      frequency of intercourse (64%). More than 50% of the patients admitted that the
      decrease in sexual function affected them considerably. Predialysis patients
      experienced less sexual dysfunction than patients undergoing active treatment.
      Women reported a minor ability to enjoy sex compared with men. No other gender
      differences in sexual dysfunction were identified in this study. No correlation
      between degree of sexual dysfunction and treatment modality or medication was
      found. CONCLUSION: A majority of the ESRD patients in this study report a
      substantial decrease in sexual desire, initiative and ability.

PMID- 18609285
TI  - Renal artery pseudoaneurysm secondary to blunt trauma nine years earlier: case
      report and review of the literature.
AB  - This report describes a 59-year-old male with a renal artery pseudoaneurysm
      secondary to blunt trauma from a snowmobile accident. The patient presented with
      haematuria and flank pain, 9 years after the injury. This is the second longest
      interval between initial trauma and aneurysm rupture in published cases. The
      diagnosis was delayed because the doctors were unaware of the initial trauma. In
      cases of haematuria, flank pain and computed tomography showing a tumour in the
      renal hilum, the patient should be questioned about previous abdominal trauma, as
      pseudoaneurysms can rupture many years after the causative injury.

PMID- 18609287
TI  - Suitability of a simplified technique based on iohexol for decentralized
      measurement of glomerular filtration rate.
AB  - OBJECTIVE: The aim of the study was to assess a simplified method for measuring
      glomerular filtration rate (GFR) using iohexol that could form the basis of a
      decentralized service for measuring GFR by sample transportation. MATERIAL AND
      METHODS: Non-fasting GFR was measured with Cr-51-EDTA and iohexol injected
      simultaneously into opposite arms (n = 110). Cubital venous blood samples,
      obtained bilaterally 20, 40, 60, 120, 180 and 240 min after injection, were
      assayed for marker injected contralaterally, Cr-51-EDTA by well-counting and
      iohexol by X-ray fluorescence. Following biexponential analysis of the clearance
      curves, GFR was measured from all six samples and also from the last three
      samples and scaled to body surface area (BSA). GFR scaled to extracellular fluid
      volume (GFR/ECV) was calculated from six samples as the mean transit time of
      marker through its distribution volume and from three samples as the clearance
      half-time. RESULTS: Cr-51-EDTA correlated closely with iohexol for measuring
      GFR/BSA (r = 0.97 for three samples, 0.94 for six). The two markers agreed more
      closely with each other in the measurement of GFR/BSA compared with GFR/ECV.
      GFR/BSA values showed better agreement with corresponding GFR/ECV values when
      they were measured with Cr-51-EDTA compared with iohexol. Six samples offered no
      significant advantage compared with three. CONCLUSIONS: Iohexol is less accurate
      than Cr-51-EDTA and scaling to BSA is more robust than scaling to ECV.
      Nevertheless, iohexol has potential to measure GFR by sample transportation,
      without having to measure injected dose. This would allow accurate measurement of
      GFR in a primary care setting.

PMID- 18609289
TI  - Iatrogenic ureteral injury due to lumbar sympathetic block.
AB  - Lumbar sympathetic block (LSB) is used in the management of sympathetically
      maintained pain states. Complications of LSB include infection, injury of spinal
      cord or somatic nerve, kidney trauma, hypotension, paraplegia and genitofemoral
      neuralgia. This report presents the case of a 53-year-old woman who had undergone
      LSB for relief of reflex sympathetic dystrophy and subsequently disrupted right
      proximal ureter. She was treated with ureteroureterostomy and indwelling ureteral
      stent.

PMID- 18609290
TI  - Feasibility of early intravesical instillation chemotherapy after transurethral
      resection of the bladder: a prospective evaluation in a consecutive series of 210
      cases.
AB  - OBJECTIVE: Early instillation chemotherapy (less than 6 h after tumour resection)
      is an accepted adjuvant treatment after transurethral resection of non-muscle
      invasive papillary bladder tumours. Because most studies have reported on
      selected patients fulfilling specific eligibility criteria, this study
      investigated the feasibility of this therapy in a non-selected, consecutive
      series of patients who had undergone transurethral surgery to the bladder at a
      single institution. MATERIAL AND METHODS: All transurethral resections of the
      bladder were prospectively evaluated. In patients with assumed non-muscle
      invasive papillary bladder cancer, resection was followed by early instillation
      of 50mg epirubicin. Practical problems, staging and cystoscopic follow-up were
      systematically registered and evaluated. RESULTS: From October 2002 to February
      2005, 210 transurethral resections (including 31 diagnostic biopsies) were
      performed in 163 patients (median age at resection 73.8 years). The following
      pathological T-stages were found: pT0 27.6%, pTa 39.0%, pT1 8.6%, > or =pT2 19.0%
      and pTis 5.7%. Patients received early instillation chemotherapy in 110 cases,
      which was generally well tolerated, but was prevented in four patients by intense
      bleeding or perforation. The treatment decision was correct in 82.8% and
      positively correlated with the experience of the treating urologist. Cumulative
      incidence rates of first postoperative tumour recurrence in the pTa group at 6,
      12 and 24 months were 6.7, 24.5 and 52.0%, respectively. CONCLUSION: Early
      instillation chemotherapy with epirubicin after transurethral resection of
      bladder tumours is generally feasible and usually has no major side-effects, but
      evaluation of intraoperative T-stage can be a problem and depends on experience.

PMID- 18609291
TI  - Effect of hydration and continuous urinary drainage on urine production in
      children.
AB  - OBJECTIVE: Although urine production depends on numerous physiological variables
      there are no quantitative data regarding the effect of bladder decompression, by
      means of continuous catheter drainage, on urine production. The aim of this study
      was to investigate this effect. MATERIAL AND METHODS: The study was carried out
      in two stages, each consisting of two phases. The effect of two distinct orally
      administered amounts of water was recorded in relation to continuous bladder
      decompression on the changes with time of urine volume and the urine production
      rate. In the first stage, 35 children were randomly divided into two groups and
      two different hydration schemes (290 and 580 ml of water/m2) were used. After the
      second urination of Phase 1, continuous drainage was employed in the phase that
      followed (Phase 2). In the second stage, a group of 10 children participated and
      Phase 2 was carried out 1 day after the completion of Phase 1. RESULTS: It was
      shown that the amount of urine produced increased in accordance with the degree
      of hydration and doubled or tripled with continual urine drainage by catheter for
      the same degree of hydration and within the same time interval. This was also
      true for Stage 2, in which Phase 2 was performed 24 h after Phase 1, indicating
      that diuresis during Phase 2 (as a result of Phase 1) was negligible. CONCLUSION:
      It was shown that during continuous drainage of urine with bladder
      catheterization there is an increased need for fluids, which should be
      administered early.

PMID- 18609292
TI  - Renal involvement in children with vesicoureteral reflux: are prenatal detection
      and surgical approaches preventive?
AB  - OBJECTIVE: Surgical correction of vesicoureteral reflux (VUR) and prolonged
      administration of antibiotics seem to lead to similar renal outcomes. However, it
      is not known whether prenatal recognition and the position of VUR modify the
      outcome in different ways. The purpose of this study was to investigate the
      effects of prenatal detection and different treatment methods on the outcome of
      unilateral refluxing renal units. PATIENTS AND METHODS: This retrospective study
      enrolled 119 children (mean age 2.8+/-3.5 years) with primary VUR. Kidney growth
      and renal function were measured with ultrasound and scintigraphy, respectively.
      To compare the ultrasound readings among patients of different ages the
      comparative-length index or index was calculated, as a percentage of the ratio of
      unilateral and the sum of bilateral renal length. RESULTS: In unilateral
      refluxing renal units there was a reduction in both index and function, whereas
      not-refluxing was increased. In the follow-up, unilateral refluxing renal units
      had a worse index, whereas not-refluxing was better. Unexpectedly, surgical
      therapy of the left-refluxing renal unit led to a reduction in the index, whereas
      its function always stayed low in diagnosis but stable. The outcome of severely
      refluxing renal units was similar after both interventions. Prenatal and
      postnatal diagnosis did not seem to modify the renal result. CONCLUSIONS: Surgery
      showed similar renal outcomes to medical treatment. A kidney growth defect from
      high-grade VUR was detected in the diagnosis. Therefore, a congenitally damaged
      kidney does not ameliorate after each treatment. Finally, prenatal detection of
      VUR does not seem to modify the outcome of the kidney significantly.

PMID- 18609293
TI  - Reliability of death certificates in prostate cancer patients.
AB  - OBJECTIVE: To evaluate the reliability of cause-of-death diagnoses among prostate
      cancer patients. MATERIAL AND METHODS: Information from death certificates
      obtained from the Swedish Death Register was compared with systematically
      reviewed medical records from the population-based Swedish Regional Prostate
      Cancer Register, South-East Region. In total, 5675 patients were included who had
      been diagnosed with prostate cancer between 1987 and 1999 and who had died before
      1 January 2003. RESULTS: The proportion of prostate cancer cases classified as
      having died from prostate cancer was 3% higher in the official death certificates
      than in the reviewed records [0.03, 95% confidence interval (CI) 0.02 to 0.04].
      Overall agreement between the official cause of death and the reviewed data was
      86% (95% CI 85 to 87%). A higher accuracy was observed among men with localized
      disease (88%, 95% CI 87 to 89%), aged 60 years or younger at death (96%, 95% CI
      93 to 100%), or who had undergone curative treatment (91%, 95% CI 88 to 95%).
      This study indicates a relatively high reliability of official cause-of-death
      statistics of prostate cancer patients in Sweden. CONCLUSION: Mortality data
      obtained from death certificates may be useful in the evaluation of large-scale
      prostate cancer intervention programmes, especially among younger patients with
      localized disease.

PMID- 18609294
TI  - Differences in adrenocortical secretory and gene expression responses to
      stimulation in vitro by ACTH or prolactin between high- and low-avoidance Hatano
      rats.
AB  - Rats of the Hatano high-avoidance (HAA) and low-avoidance (LAA) strains have been
      genetically selected on the basis of their two-way active avoidance behavior, and
      have different endocrine responses to stress. The present study focused on the
      adrenal steroid hormone responses of the Hatano strains and identifies
      differences in regulation of the adrenal cortex in vitro of HAA and LAA rats.
      Although incubation with prolactin (PRL) and/or adrenocorticotrophic hormone
      (ACTH) resulted in a dose-dependent increase of corticosterone and progesterone
      release by adrenal cells from both HAA and LAA male rats, the responses were
      markedly increased for adrenal cells from LAA rats as compared with HAA rats.
      This finding suggested that adrenal glands of HAA rats are less sensitive to PRL
      and/or ACTH than adrenals from LAA rats. Several possible intra-adrenal
      regulators were investigated. The basal level of expression of steroidogenic
      acute regulatory protein (StAR) and the long form of the PRL receptor (PRLR-L)
      mRNAs was higher in adrenals of LAA rats. ACTH treatment of adrenal cells from
      HAA rats resulted in statistically significant increases in melanocortin receptor
      2 (MC2R) mRNA expression, while neither ACTH nor PRL altered MC2R mRNA expression
      in adrenal cells of LAA rats. Conversely, the increase in PRLR-L mRNA expression
      induced by PRL was observed only in adrenal cells from LAA rats. Treatment of
      adrenal cells with PRL and/or ACTH increased the expression of StAR and CYP11A1
      mRNAs for both Hatano strains. However, the induction of StAR mRNA expression was
      higher in LAA rats, but the CYP11A1 response was lower. These findings indicate
      that adrenal cells of the LAA strain have higher sensitivity to secretagogues
      than those of the HAA strain. These results suggest that PRL may also be
      important in stimulating secretion of adrenal steroid hormones.

PMID- 18609296
TI  - Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats:
      implications for neurodegenerative disorders.
AB  - Many studies have shown that early life stress may lead to impaired brain
      development, and may be a risk factor for developing psychiatric pathologies such
      as depression. However, few studies have investigated the impact that early life
      stress might have on the onset and development of neurodegenerative disorders,
      such as Parkinson's disease, which is characterized in part by the degeneration
      of dopaminergic neurons in the nigrostriatal pathway. The present study subjected
      rat pups to a maternal separation paradigm that has been shown to model adverse
      early life events, and investigated the effects that it has on motor deficits
      induced by a unilateral, intrastriatal injection of 6-hydroxydopamine (12
      microg/4 microl). The female rats were assessed for behavioral changes at 28 days
      post-lesion with a battery of tests that are sensitive to the degree of dopamine
      loss. The results showed that rats that had been subjected to maternal separation
      display significantly impaired performance in the vibrissae and single-limb
      akinesia test when compared to normally reared animals. In addition, there was a
      significant increase in the loss of tyrosine hydroxylase staining in maternally
      separated rats. Our results therefore suggest that adverse experiences sustained
      during early life contribute to making dopamine neurons more susceptible to
      subsequent insults occurring during more mature stages of life and may therefore
      play a role in the etiopathogenesis of Parkinson's disease.

PMID- 18609295
TI  - Hypothalamic-pituitary-adrenal axis dysregulation and behavioral analysis of
      mouse mutants with altered glucocorticoid or mineralocorticoid receptor function.
AB  - Corticosteroid receptors are critical for the maintenance of homeostasis after
      both psychological and physiological stress. To understand the different roles
      and interactions of the glucocorticoid receptor (GR) and mineralocorticoid
      receptor (MR) during stress, it is necessary to dissect the role of
      corticosteroid signaling at both the system and sub-system level. A variety of GR
      transgenic mouse lines have recently been used to characterize the role of GR in
      the CNS as a whole and particularly in the forebrain. We will describe both the
      behavioral and cellular/molecular implications of disrupting GR function in these
      animal models and describe the implications of this data for our understanding of
      normal endocrine function and stress adaptation. MRs in tight epithelia have a
      long established role in sodium homeostasis. Recently however, evidence has
      suggested that MRs in the limbic brain also play an important role in
      psychological stress. Just as with GR, targeted mutations in MR induce a variety
      of behavioral changes associated with stress adaptation. In this review, we will
      discuss the implications of this work on MR. Finally, we will discuss the
      possible interaction between MR and GR and how future work using double mutants
      (through conventional means or virus based gene alteration) will be needed to
      more fully understand how signaling through these two steroid receptors provides
      the adaptive mechanisms to deal with a variety of stressors.

PMID- 18609297
TI  - Chronic restraint stress impairs T-cell immunity and promotes tumor progression
      in mice.
AB  - Long-term exposure to stressful situations can affect the immune system. The T
      cell response is an important component of anti-tumoral immunity. Hence,
      impairment of the immune function induced by a chronic stressor has been
      postulated to alter the immunosurveillance of tumors, thus leading to a worse
      neoplastic prognosis. Here, we show that chronic restraint stress affects T-cell
      mediated immunity in mice. This was evidenced by a decrease of mitogen-induced T
      cell proliferation, a reduction in CD4(+)T lymphocyte number and a decrease of
      tumor necrosis factor-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma)
      production in stressed mice. Additionally, mice subjected to chronic restraint
      stress displayed an enhancement of tumor growth in a syngeneic lymphoma model,
      i.e. an increase of tumor proliferation and a reduction of animal survival.
      Finally, stressed mice had a reduced specific cytotoxic response against these
      tumor cells. These results suggest that chronic exposure to stress promotes
      cancer establishment and subsequent progression, probably by depressing T-cell
      mediated immunity. The T-cell immunity impairment as well as the tumor
      progression enhancement emphasize the importance of the therapeutic management of
      stress to improve the prognosis of cancer patients.

PMID- 18609299
TI  - Stress in cynomolgus monkeys (Macaca fascicularis) subjected  to long-distance
      transport and simulated transport housing conditions.
AB  - The stress associated with transportation of non-human primates used in
      scientific research is an important but almost unexplored part of laboratory
      animal husbandry. The procedures and routines concerning transport are not only
      important for the animals' physical health but also for their mental health as
      well. The transport stress in cynomolgus monkeys (Macaca fascicularis) was
      studied in two experiments. In Experiment 1, 25 adult female cynomolgus monkeys
      were divided into five groups of five animals each that received different diets
      during the transport phase of the experiment. All animals were transported in
      conventional single animal transport cages with no visual or tactile contact with
      conspecifics. The animals were transported by lorry for 24 h at ambient
      temperatures ranging between 20 degrees C and 35 degrees C. Urine produced
      before, during and after transport was collected and analysed for cortisol by
      enzyme-linked immunosorbent assay (ELISA). All monkeys exhibited a significant
      increase in cortisol excretion per time unit during the transport and on the
      first day following transport.Although anecdotal reports concerning diet during
      transport, including the provision of fruits and/or a tranquiliser, was thought
      likely to influence stress responses, these were not corrobated by the present
      study. In Experiment 2, behavioural data were collected from 18 cynomolgus
      macaques before and after transfer from group cages to either single or pair
      housing, and also before and after a simulated transport, in which the animals
      were housed in transport cages. The single housed monkeys were confined to single
      transport cages and the pair housed monkeys were kept in their pairs in double
      size cages. Both pair housed and singly housed monkeys showed clear behavioural
      signs of stress soon after their transfer out of their group cages.However,
      stress-associated behaviours were more prevalent in singly housed animals than in
      pair housed animals, and these behaviours persisted for a longer time after the
      simulated transport housing event than in the pair housed monkeys. Our data
      confirm that the transport of cynomolgus monkeys is stressful and suggest that it
      would be beneficial for the cynomolgus monkeys to be housed and transported in
      compatible pairs from the time they leave their group cages at the source country
      breeding facility until they arrive at their final laboratory destination in the
      country of use.

PMID- 18609298
TI  - Angiotensin II AT(1) receptor blockade selectively enhances brain AT(2) receptor
      expression, and abolishes the cold-restraint stress-induced increase in tyrosine
      hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats.
AB  - Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated
      orally for 14 days with the AT(1) receptor antagonist candesartan before
      submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased
      AT(1) receptor binding in the median eminence and basolateral amygdala, increased
      AT(2) receptor binding in the medial subnucleus of the inferior olive, decreased
      AT(2) binding in the ventrolateral thalamic nucleus and increased tyrosine
      hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT(1)
      receptor blockade reduced AT(1) receptor binding in all areas studied and
      enhanced AT(2) receptor binding in the medial subnucleus of the inferior olive.
      Candesartan pretreatment produced a similar decrease in brain AT(1) binding after
      stress, and prevented the stress-induced AT(2) receptor binding decrease in the
      ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT(1)
      blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA
      level. Our results demonstrate that oral administration of candesartan
      effectively blocked brain AT(1) receptors, selectively increased central AT(2)
      receptor expression and prevented the stress-induced central stimulation of
      tyrosine hydroxylase transcription. The present results support a role of brain
      AT(1) and AT(2) receptors in the regulation of the stress response, and the
      hypothesis that AT(1) receptor antagonists may be considered as potential
      therapeutic compounds in stress related disorders in addition to their anti
      hypertensive properties.

PMID- 18609300
TI  - The paraventricular nucleus of the hypothalamus is involved in cardiovascular
      responses to acute restraint stress in rats.
AB  - The paraventricular nucleus of the hypothalamus (PVN) has been implicated in
      several aspects of cardiovascular control. Stimulation of the PVN evokes changes
      in blood pressure and heart rate. Additionally, this brain area is connected to
      several limbic structures implicated in behavioral control, as well as to
      forebrain and brainstem structures involved in cardiovascular control. This
      evidence indicates that the PVN may modulate cardiovascular correlates of
      behavioral responses to stressful stimuli. Acute restraint is an unavoidable
      stressor that evokes marked and sustained cardiovascular changes, which are
      characterized by elevated mean arterial pressure (MAP) and an intense heart rate
      (HR) increase. We report on the effect of inhibition of PVN synapses on MAP and
      HR responses evoked by acute restraint in rats. Bilateral microinjection of the
      nonspecific synaptic blocker cobalt (CoCl(2), 1 mM/100 nl) into the PVN did not
      change the HR response or the initial peak of the MAP response to restraint
      stress, but reduced the area under the curve of the MAP response. Moreover,
      bilateral microinjection of cobalt in areas surrounding the PVN did not change
      the cardiovascular response to restraint. These results indicate that synapses in
      the PVN are involved in the neural pathway that controls blood pressure changes
      evoked by restraint.

PMID- 18609301
TI  - Elevated content of cortisol in hair of patients with severe chronic pain: a
      novel biomarker for stress.
AB  - Hair analysis has been used to reflect long-term systemic exposure to exogenous
      drugs and toxins. Several studies have demonstrated the feasibility of measuring
      endogenous steroid hormones, e.g. cortisol, in hair. Recently, a study in
      macaques showed a significant increase in hair cortisol levels induced by stress.
      We explored whether hair cortisol levels may be used as a biomarker for long-term
      stress in humans. Patients with severe chronic pain, aged 18 years or older,
      receiving opioid treatment for at least one year were recruited. Controls were
      non-obese (body mass index, BMI < 30 mg/kg(2)) adults. The Perceived Stress Scale
      (PSS) questionnaire was used to assess perceived stress over the last 4 weeks. A
      hair sample was obtained from the vertex posterior. Cortisol was measured using
      an enzyme-linked immunosorbent assay. We included fifteen patients (nine females
      and six males) and 39 non-obese control subjects (20 females, 19 males). PSS
      scores (median and range) were significantly higher in chronic pain patients (24:
      12-28) than in controls (12: 3-31)(P < 0.001). Hair cortisol contents (median and
      range) were significantly greater in chronic pain patients (83.1: 33.0-205 g/mg)
      than in controls (46.1: 27.2-200 pg/mg) (P < 0.01). We conclude that hair
      cortisol contents are increased in patients with major chronic stress.
      Measurement of cortisol levels in hair constitutes a novel biomarker of prolonged
      stress.

PMID- 18609302
TI  - Exposure to a stressor produces a long lasting enhancement of fear learning in
      rats.
AB  - In contextual fear conditioning, footshock is given in a context, and re-exposure
      to this context elicits the conditional defensive response of freezing, a
      reliable behavioral index of conditional fear. Normally, the amount of contextual
      freezing is directly proportional to the number of shocks an animal receives in
      the context. However, pre-exposure to a stressor can produce an enhancement in
      conditional freezing. Pre-exposure to repeated footshock in one context produces
      an enhancement of conditional freezing to cues associated with a single shock in
      a second distinct context. This model of stress-enhanced fear learning (SEFL) can
      be utilized to study how stress affects learning of future aversive events. The
      experiments in this paper characterize the magnitude and longevity of SEFL. In
      the first experiment, the number of footshocks given during the pre-exposure
      session was varied and conditional fear to the single shock was assessed. Pre
      exposure to 1 shock did not produce an enhancement in fear learning in the second
      context, but pre-exposure to 4 or 15 shocks did. The time-course of the
      enhancement was examined in the next two experiments. These experiments show that
      SEFL persists for at least 3 months.

PMID- 18609303
TI  - Effects of exposure of mice to hindlimb unloading on leukocyte subsets and
      sympathetic nervous system activity.
AB  - The hindlimb unloading (HU) rodent model was developed to simulate some of the
      aspects of spaceflight conditions. Our previous studies showed that exposure to
      HU for 48 h (h) followed by bacterial challenge, reduces the ability of mice to
      resist infection. The purpose of this study was to investigate the physiological
      changes in mice during the 48 h of exposure to HU to understand the mechanisms
      involved in the increased susceptibility to infection observed in mice subjected
      to these conditions. Female Swiss Webster mice were hindlimb-unloaded during 48
      h. Blood samples, spleen and peritoneal cells were removed before and after 18 or
      48 h of HU-exposure. Leukocyte subset analysis was performed in spleen and
      peritoneal cells by flow cytometry, and catecholamine levels were measured in
      plasma and whole spleen by a catecholamine enzyme immunoassay. Catecholamine
      levels measured in plasma and spleen were significantly greater in mice exposed
      to HU compared to control. This increase coincided with significant reductions in
      spleen size in the HU group. Flow cytometric analyses showed a significant
      reduction of splenic CD19 + B-cells and NK1.1+ cells in mice exposed to HU with a
      concomitant increase in T-cells. These results suggest that exposure to HU
      increases the activity of the sympathetic nervous system (SNS) and induces
      lymphocyte sub-population changes that may contribute to the deregulation of
      immunity seen in mice exposed to HU and, more importantly may predispose the
      otherwise healthy host to the subsequent reduced ability to resist infections.

PMID- 18609304
TI  - Resilience and hypothalamic-pituitary-adrenal axis reactivity under acute stress
      in young men.
AB  - The present study examined the relationship between resilience (measured using
      the Resilience Scale for Adults) and hypothalamic-pituitary-adrenal (HPA) axis
      reactivity. We examined the subjective and cortisol responses of 28 healthy young
      men to an acute stressor (public speech task). Eight saliva samples were
      collected in order to obtain the response curve (anticipation, reactivity,
      recuperation) for each subject. ANOVA indicated that highly resilient individuals
      tended to display less mood deterioration than less resilient individuals
      (marginal p(time x group interaction) = 0.075). They also revealed that the
      former tended to secrete less cortisol overall than the latter during the
      experiment (marginal p(main group effect) = 0.087) but this effect was not
      uniform across time (p(time x group interaction) = 0.029). Additional analyses
      performed to identify the source of this interaction revealed that resilience
      moderates cortisol secretion in anticipation of the stressor (i.e. highly
      resilient individuals secreted less cortisol than less resilient ones, p = 0.05)
      but that it is not conductive to lower HPA reactivity amidst stress (i.e. there
      was no difference between groups in the increase in cortisol secretion from
      baseline to peak). The recovery slopes were likewise not statistically different.
      The implications of these findings regarding health are discussed.

PMID- 18609305
TI  - Effects of social isolation and environmental enrichment on atherosclerosis in
      ApoE-/- mice.
AB  - Social support and a stimulating environment have been suggested to reduce stress
      reactions and cardiovascular risk. The aim of this study was to assess the role
      of environmental enrichment and social interaction for development of
      atherosclerosis in atherosclerosis prone mice. Male ApoE-/- mice were divided
      into four groups and followed during 20 weeks: (i) enriched environment (E,
      n=12), (ii) deprived environment (ED, n=12), (iii) enriched environment with
      exercise (E-Ex, n=12) and (iv) socially deprived by individual housing (SD,
      n=10). Plasma lipid and cytokine concentrations were measured. Atherosclerosis
      was quantified in cross-sections of innominate artery and en face in thoracic
      aorta. Plaque area was significantly increased in SD mice in the innominate
      artery (P<0.05 vs. all other groups), but not in the thoracic aorta. Plasma
      lipids were increased in SD mice (P<0.001 vs. all for total cholesterol, P<0.05
      vs. E and P<0.01 vs. ED for triglycerides). Plasma concentration of granulocyte
      colony stimulating factor (G-CSF) was decreased in SD mice compared to E mice
      (P<0.05). Thus, social isolation increased atherosclerosis and plasma lipids in
      ApoE-/- mice. Reduction in plasma G-CSF levels may hamper endothelial
      regeneration in the atherosclerotic process. While environmental enrichment did
      not affect atherosclerosis, social isolation accelerated atherosclerosis.

PMID- 18609306
TI  - Women with diarrhoea-predominant irritable bowel syndrome show an increased
      pressure response to 35% carbon dioxide stress challenge.
AB  - The responses to inhalation of 35% carbon dioxide (CO(2)) as a stressor were
      compared in female irritable bowel syndrome (IBS) patients and healthy controls
      to assess potential differences in cardiovascular, neuroendocrine and behavioural
      responses to stress. A total of 22 women (12 patients with ROME II defined
      diarrhoea-predominant IBS and 10 aged-matched controls) were challenged with a
      single vital capacity breath of 35% CO(2) (with 65% oxygen). Beat-to-beat blood
      pressure and heart rate were recorded prior to, during and after the inhalation.
      Serum cortisol concentration and behavioural ratings were measured pre- and post
      inhalation. A typical pattern of responses to CO(2) was observed, characterised
      by a reduction in heart rate and increases in serum cortisol and anxiogenic
      symptoms; however, these responses did not differ between groups. Both groups
      also demonstrated an increase in systolic blood pressure; however, this response
      was significantly enhanced in IBS patients compared to healthy controls (P <
      0.05). These findings demonstrate that females with diarrhoea-predominant IBS
      have an exaggerated pressor response to 35% CO(2) stress challenge, suggesting a
      more stress-responsive sympathetic nervous system.

PMID- 18609309
TI  - Three definitions of metabolic syndrome applied to a sample of young obese men
      and their relation with plasma testosterone.
AB  - This study tested 60 men, aged <40 years, with a BMI 27-35 kg/m(2) to determine
      whether they had metabolic syndrome. The three definitions used to test this were
      from the National Cholesterol Education Program (NCEP), the World Health
      Organization (WHO) and the International Diabetes Federation (IDF). Further, the
      relationship between a positive definition and plasma testosterone (T) and
      calculated free T was analysed. Using the above three definitions of metabolic
      syndrome (MetS), there was a large degree of overlap of identifying obese men as
      having the syndrome, but there were quantitatively significant differences as
      well. So, it is relevant in studies to identify which of the present definitions
      of the syndrome has been used. With aging there is an increasing prevalence of
      the syndrome and age itself might be a factor in the lower T levels encountered
      in these men. But low plasma total T and calculated free T were also consistent
      features of men <40 years with metabolic syndrome, regardless of which definition
      had been applied. Including low T levels in the definition of metabolic syndrome,
      may be helpful.

PMID- 18609310
TI  - LOH-pitfalls of an ambiguous abbreviation.

PMID- 18609307
TI  - Intergenerational effects of cocaine on maternal aggressive behavior  and brain
      oxytocin in rat dams.
AB  - Gestational cocaine treatment results in significantly increased maternal
      aggression towards an intruder by postpartum day six, while acute postpartum
      treatment dose dependently decreases maternal aggressive (MA) behavior. Both
      increased and decreased aggression in the cocaine-treated dams are correlated
      with either decreased or increased levels of oxytocin in the amygdala,
      respectively. The current study was an effort to determine whether the effect of
      gestational cocaine on maternal aggression is transient or would continue into
      the postpartum period; whether an intermittent cocaine treatment regimen, which
      incorporates gestational and postpartum intermittent cocaine treatment, would
      differ from chronic daily gestational treatment; and finally, whether next
      generation female offspring of cocaine-treated or control dams would have altered
      MA behavior and oxytocin system changes attributable to either prenatal drug
      exposure, rearing condition or both. We now report no increase in maternal
      aggression following chronic gestational treatment and significantly lower levels
      of aggression in intermittently treated dams on postpartum day eight, with no
      significant effects in either group on postpartum day 12. Young adult female
      offspring of the cocaine-treated and control dams, who reared their own natural
      litters and were tested on postpartum day eight for maternal aggression, had
      higher levels of maternal aggression towards an intruder attributable to both
      prenatal cocaine exposure and rearing condition. Higher aggression in cocaine
      reared next generation dams was associated with lower levels of oxytocin in the
      amygdala. Intergenerational effects of cocaine were apparent with respect to
      aggression and oxytocin system changes.

PMID- 18609311
TI  - The Open-Trial Selective Reminding Test (OT-SRT) as a tool for the assessment of
      learning and memory.
AB  - The Open Trial Selective Reminding Test (OT-SRT) is a modification of the SRT
      that also evaluates new learning abilities. The examinee is asked to learn a list
      of 10 words over a maximum of 15 trials. Using a criterion-referenced approach,
      the list is repeatedly administered until a criterion of complete recall on two
      consecutive trials is achieved. Training to criterion provides a better
      assessment of learning ability than the traditional fixed trial list-learning
      paradigm. Recall and recognition is then tested 30 and 90 minutes following the
      learning trials. This paper presents normative data on the OT-SRT for 117 healthy
      controls (Study 1) and 151 participants with clinically definite multiple
      sclerosis (Study 2).

PMID- 18609312
TI  - Neuropsychological profile of a Filipino gentleman with X-linked dystonia
      parkinsonism: a case report of Lubag disease.
AB  - X-Linked Dystonia-Parkinsonism (XDP or "Lubag") is a progressive
      neurodegenerative disorder unique to the Island of Panay in the Philippines.
      Imaging and autopsy studies have suggested involvement of the caudate and putamen
      in late stages. Because the clinical presentation of patients with XDP resembles
      that of patients with Parkinson disease or dystonia, it is reasonable to predict
      the neuropsychological profile might be similar; however, the neuropsychological
      profile of a XDP patient has not previously been published. We present the
      neuropsychological findings of a 67-year-old gentleman with a 10-year history of
      XDP who presented with parkinsonian and dystonic symptoms. He was evaluated for
      suitability for deep brain stimulation surgery. Neuropsychological findings
      demonstrated diffuse impairment involving memory, visuospatial, language, and
      executive functioning.

PMID- 18609313
TI  - Normative data on and psychometric properties of Verbal and Visual Indexes of the
      RBANS in older adults.
AB  - The original structure of the RBANS includes five Indexes; however, recent factor
      analyses support a two-factor solution (Duff et al., 2006; Wilde, 2006).
      Unfortunately, normative and psychometric data do not currently exist on these
      two new Indexes. Building on prior work, the current study provides age- and
      education-corrected normative data to calculate the factor-derived Verbal and
      Visual RBANS Indexes (Duff et al., 2006) in a large cohort (n = 718) of older
      adult primary care patients. Psychometric data (e.g., discrepancy scores,
      internal consistency, retest reliability) on these new Indexes are also
      presented. These data might allow clinicians and researchers to better assess
      laterality effects of brain dysfunction when using the RBANS, although clinical
      validation is needed.

PMID- 18609315
TI  - Differential sensitivity of the Response Bias Scale (RBS) and MMPI-2 validity
      scales to memory complaints.
AB  - The MMPI-2 Response Bias Scale (RBS) is designed to detect response bias in
      forensic neuropsychological and disability assessment settings. Validation
      studies have demonstrated that the scale is sensitive to cognitive response bias
      as determined by failure on the Word Memory Test (WMT) and other symptom validity
      tests. Exaggerated memory complaints are a common feature of cognitive response
      bias. The present study was undertaken to determine the extent to which the RBS
      is sensitive to memory complaints and how it compares in this regard to other
      MMPI-2 validity scales and indices. This archival study used MMPI-2 and Memory
      Complaints Inventory (MCI) data from 1550 consecutive non-head-injury disability
      related referrals to the first author's private practice. ANOVA results indicated
      significant increases in memory complaints across increasing RBS score ranges
      with large effect sizes. Regression analyses indicated that the RBS was a better
      predictor of the mean memory complaints score than the F, F(B), and F(P) validity
      scales and the FBS. There was no correlation between the RBS and the CVLT, an
      objective measure of verbal memory. These findings suggest that elevated scores
      on the RBS are associated with over-reporting of memory problems, which provides
      further external validation of the RBS as a sensitive measure of cognitive
      response bias. Interpretive guidelines for the RBS are provided.

PMID- 18609316
TI  - Examination of the impact of ethnicity on the Minnesota Multiphasic Personality
      Inventory-2 (MMPI-2) Fake Bad Scale.
AB  - The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Fake Bad Scale (FBS;
      Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) has been shown to be
      sensitive to somatic over-endorsement. However, the impact of ethnicity has not
      been examined on the FBS, which is of concern given some studies that show
      increased rates of somatic endorsement in particular ethnic groups. We evaluated
      the FBS performance of 190 Caucasian American, Hispanic, and African American
      outpatients who were obtained from two different clinical settings, excluding
      those who were applying for disability or in litigation. We failed to find
      significant ethnic differences in mean FBS performance or in cut-off specificity
      rates. We did find evidence of a gender effect, supporting continued use of
      gender-specific FBS cutoffs.

PMID- 18609314
TI  - Process examination of executive function in ADHD: sex and subtype effects.
AB  - To examine effects of group (Attention-Deficit/Hyperactivity Disorder [ADHD]
      versus Typically Developing [TD]), sex, and ADHD subtype on "process/optional"
      measures of executive functioning, children (n = 123; 54 ADHD, 69 TD) aged 8-16
      completed subtests from the D-KEFS. No group, sex, or ADHD subtype effects were
      found on optional measures from the Trail Making, Color-Word Interference, and
      Tower tests. A significant interaction was found for Verbal Fluency Total
      Repetition Errors; boys with Combined/Hyperactive-Impulsive (ADHD-C/HI) type ADHD
      performed better than ADHD-C/HI girls, whereas girls with Inattentive type ADHD
      (ADHD-I) performed better than ADHD-I boys. Overall, children with ADHD did not
      differ from TD on most optional measures from the D-KEFS. When sex and ADHD
      subtype were considered, children with the subtype of ADHD less common for sex
      were at greater risk for poorer performance.

PMID- 18609317
TI  - Annualized functional change in Alzheimer's disease participants and normal
      controls.
AB  - The rate of functional change in persons with mild Alzheimer's disease (AD) was
      compared to that of cognitively normal elderly control subjects. A comparison of
      annualized rates of change on the Test of Everyday Functional Abilities (TEFA)
      was carried out, along with a brief measure of instrumental activities of daily
      living skills, in persons with mild AD (Mini-Mental State Exam score >20) and
      cognitively normal elderly controls. Persons with AD (N = 30) showed an 8.5 %
      (3.5 point) annualized decline in TEFA scores over an average of 1.2 years; there
      was no decline in a group of elderly normal controls (N = 20) over an average of
      1.5 years. Persons with mild AD showed functional changes over the course of a
      year on a direct measure of instrumental activities of daily living; a comparable
      group of normally aging persons did not.

PMID- 18609318
TI  - Neuropsychological consultation with school personnel: what clinical
      neuropsychologists need to know.
AB  - Schools request consultation from neuropsychologists employed outside the school
      setting to enhance assessment and intervention for children with neurological,
      medical, and psychological conditions. The legislative and administrative
      parameters governing special education services for exceptional children most
      pertinent to the consulting neuropsychologist are examined. The role of the
      school-based multidisciplinary team in determining eligibility for special
      education is discussed. Potential roles for the clinical neuropsychologist on the
      school-based team and approaches to interprofessional collaboration between
      clinical neuropsychologists and school psychologists are presented. Reimbursement
      for services and ethical considerations are also discussed.

PMID- 18609319
TI  - Brain injury severity, litigation status, and self-report of postconcussive
      symptoms.
AB  - The Postconcussive Symptom Questionnaire (PCSQ) was developed to assess the
      symptoms associated with the controversial diagnosis of postconcussion syndrome.
      We examined item endorsement on the PCSQ in two groups. The first group was made
      up of individuals diagnosed with moderate to severe traumatic brain injury. The
      second group was made up of individuals meeting criteria for mild traumatic brain
      injury who exhibited no evidence of neurological injury. In addition, they
      demonstrated poor effort during neuropsychological examination. Significant
      differences in item endorsement were found the majority of individual items as
      well as on the PCSQ indices. The poor effort mild traumatic brain injury group
      consistently reported more symptoms with greater severity. The results raise
      further questions about the validity of postconcussion symptoms.

PMID- 18609320
TI  - Effects of examiner error on neuropsychological test results in a multi-site
      study.
AB  - This study compared the difference between original and "corrected"
      neuropsychological test scores at baseline and following 1 year of experience in
      17 non-psychology trained examiners. Test protocols were reviewed for errors in
      instruction, administration, recording, and scoring. Fewer than 3% of the test
      scaled scores showed a correction of greater than 1 SD. At baseline, individual
      test scores that changed T-score classification occurred on Digit Symbol, Trails
      B, and Logical Memory I and II. At one year, significant classification changes
      remained for Logical Memory I and II (25% and 15%). Scoring of subjective tests
      remains problematic and centralized re-scoring is recommended.

PMID- 18609322
TI  - Literacy-based normative data for low socioeconomic status African Americans.
AB  - Clinical neuropsychology relies on the use of appropriate test norms. Normative
      studies frequently stratify based on age, education, sex, and race. None to date
      has reported norms based on literacy, despite the substantial evidence that
      literacy impacts cognitive functioning. Some researchers have suggested that
      literacy is a more accurate reflection of academic achievement and quality of
      education than years of education, particularly for African Americans. The
      current study provides literacy-based normative data for multiple
      neuropsychological measures based on a sample of predominantly low socioeconomic
      status African Americans. These normative data should improve the diagnostic
      accuracy of performances by African-American clients with similar demographic
      backgrounds.

PMID- 18609323
TI  - Assessment of depression in three medically ill, elderly populations: Alzheimer's
      disease, Parkinson's disease, and stroke.
AB  - Prevalence rates of depression in medically ill elderly people are strikingly
      high. In particular, the prevalences of depression at any given time in
      Alzheimer's, Parkinson's, and stroke are as high as 87%, 75%, and 79%,
      respectively. Proper detection and management of depression in primary care is
      imperative. The present review examines the risk factors, peculiarities, and
      etiologies of depression in these populations. We suggest that certain features
      of depression be considered in assessing depression in these populations and
      provide guidelines for distinguishing depression from medical, psychosocial, and
      physical complaints common in elderly people. Additionally, we explore the use of
      self-report instruments of depression and provide guidelines regarding the
      specific measures and cutoffs most appropriate for use with these populations. To
      this end, we hope that readers acquire a greater appreciation for the experience
      of depression of those suffering from these neurological disorders to aid in
      their assessment.

PMID- 18609324
TI  - The vulnerability to coaching across measures of effort.
AB  - Neuropsychologists are increasingly called upon to conduct evaluations with
      individuals involved in personal injury litigation. While the inclusion of
      measures of effort within a test battery may help clinicians determine whether a
      client has put forth full effort, attorney coaching may allow dishonest clients
      to circumvent these efforts. The purpose of this study was to determine the
      degree to which frequently used measures of effort are susceptible to coaching,
      as well as to explore and classify strategies undertaken by coached malingering
      simulators. Overall, coached simulators performed significantly better on 7 of 14
      measured variables. Potential improvements in the external validity of the
      simulation design were also explored.

PMID- 18609325
TI  - Comparison of the MMPI-2 restructured Demoralization Scale, Depression Scale, and
      Malingered Mood Disorder Scale in identifying non-credible symptom reporting in
      personal injury litigants and disability claimants.
AB  - A known groups design compared the ability of the 24-item MMPI-2 Restructured
      Clinical Demoralization Scale (RCd), the 57-item Depression Scale (Scale 2), and
      the 15-item Malingered Mood Disorder Scale (MMDS) to identify non-credible
      symptom response sets in 84 personal injury litigants and disability claimants
      compared to 77 non-litigating head-injured controls. All three scales showed
      large effect sizes (>0.80). Scale 2 was associated with the largest effect size
      (2.19), followed by the MMDS (1.65), and the RCd (0.85). Logistic regression
      analyses revealed that a cutscore of > or =28 on the 57-item Scale 2 was
      associated with high specificity (96.1%) and sensitivity (76.2%), while a
      cutscore of > or =16 on the 24-item RCd was less accurate (87% specificity and
      50% sensitivity). Cutscores for the MMDS were not calculated as they were
      reported in a previous study. Results indicated that like the 15-item MMDS, the
      57-item MMPI-2 Scale 2 may provide another empirically derived index with known
      error rates upon which examiners may rely to investigate hypotheses relative to
      exaggeration of illness-related behavior and impression management in forensic
      contexts involving PI litigants and disability claimants.

PMID- 18609326
TI  - Classification accuracy and predictive ability of the medical symptom validity
      test's dementia profile and general memory impairment profile.
AB  - When assessing symptom validity in patients with dementia, traditional approaches
      may be inappropriate because neurological factors may cause altered performance.
      The Medical Symptom Validity Test has a Dementia Profile that explicitly
      recognizes this fact. We prospectively evaluated classification accuracy of the
      Dementia Profile for 52 referrals to a memory disorders clinic. The Dementia
      Profile correctly classified 36/52 patients. Sensitivity was 54.8%, specificity
      was 90.5%, positive predictive value was 89.5%, negative predictive value was
      60.0%, and the likelihood ratio was 5.77. Of 31 patients with dementia, 11 did
      not fail symptom validity indices. When only considering patients who failed
      symptom validity indices, sensitivity of the Dementia Profile was 85%.
      Classification accuracy statistics are also provided for the Genuine Memory
      Impairment Profile.

PMID- 18609327
TI  - Understanding the neuropsychological profile of HIV+ participants with low
      literacy: role of the General Ability Measure for Adults (GAMA).
AB  - The WRAT-3 Reading subtest (WRS) may be inappropriate in diseases having
      disproportionate impact on populations with educational disadvantages (i.e.,
      HIV/AIDS). To understand how low literate individuals would perform on an IQ test
      requiring minimal education, the General Ability Measure for Adults (GAMA) was
      studied. HIV+ participants completed WRS, GAMA, and neuropsychological tests.
      Participants with low WRS (<80 SS) but higher GAMA (>or=80 SS) had significantly
      better overall neuropsychological functioning than those with <80 SS on both
      tests. The GAMA may be a useful test when disparities in educational quality
      render reading-based measures of IQ a poor surrogate of premorbid function.

PMID- 18609328
TI  - Malingering detection with the Wisconsin Card Sorting Test in mild traumatic
      brain injury.
AB  - This study evaluates the ability of several Wisconsin Card Sorting Test (WCST;
      Psychological Assessment Resources, 1990) variables to detect malingering in mild
      traumatic brain injury (TBI). The sample consisted of 373 TBI patients and 766
      general clinical patients. Classification accuracy for seven indicators is
      reported across a range of injury severity and scores levels. Overall, most WCST
      scores were ineffective in discriminating malingering from non-malingering mild
      TBI patients. Failure-to-Maintain-Set, the Suhr & Boyer formula, and the King et
      al. formula detected about 30% of malingerers at cutoffs associated with a false
      positive error rate of < or =11%. The clinical interpretation and use of these
      indicators are discussed.

PMID- 18609330
TI  - A description of preschool neuropsychological assessment in the P.I.N.T. Clinic
      after the first 5 years.
AB  - Assessment of preschool-aged children constitutes a dilemma for many
      neuropsychologists because of a limited set of standardized measures with
      normative data as well as inadequate understanding of typical developmental
      trajectories for neuropsychological functions during the first years of life.
      However, numerous neurological disorders, medical disorders with central nervous
      system involvement, and even psychiatric disorders have their onset during this
      time and subsequently impact cognition by altering functional developmental
      trajectories. Comprehensive neuropsychological evaluations can help to delineate
      this alteration in developmental trajectory and assist in determining need for
      specific interventions services so that they can be implemented early as possible
      in hopes of reducing developmental cognitive impairments. In this descriptive
      report, potential preschool neuropsychological evaluation procedures are
      described and a discussion of appropriate reasons for referral and pertinent
      testing considerations is presented. Additionally, the Preschool and Infant
      Neuropsychology (P.I.N.T.) Clinic is presented to describe a methodology for
      conducting preschool neuropsychological assessment.

PMID- 18609331
TI  - Mayo older americans normative studies: factor analysis of an expanded
      neuropsychological battery.
AB  - The Mayo Cognitive Factor Scores were derived from a "core battery" consisting of
      the WAIS-R, WMS-R, and Auditory Verbal Learning Test. The present study sought to
      clarify the factor structure of an expanded neuropsychological battery in normal
      elderly controls. Confirmatory factor analysis was performed on the WAIS-III,
      WRAT-3 Reading, Boston Naming Test, Controlled Oral Word Association Test,
      Category Fluency, Rey-Osterreith Complex Figure, Visual Form Discrimination, and
      Trail Making Test A & B. A base four-factor model consistent with the WAIS-III
      factor structure was utilized. Only one novel five-factor model differentiating
      processing and motor speed tests improved upon this base model. Other models did
      not, including a factor for executive function, division of
      construction/visuospatial ability, or "hold"/"no hold" language abilities.

PMID- 18609332
TI  - Dementia and effort test performance.
AB  - Research on the performance of patients with dementia on tests of effort is
      particularly limited. We examined archival data from 214 non-litigating patients
      with dementia on 18 effort indices derived from 12 tests (WAIS-III/WAIS-R Digit
      Span and Vocabulary, Dot Counting Test, Warrington Recognition Memory Test-Words,
      WMS-III Logical Memory, Rey Word Recognition Memory Test, Finger Tapping, b-Test,
      Rey 15-Item, Test of Memory Malingering, Rey Auditory Verbal Learning Test, and
      Rey Complex Figure Test). Results indicated that recommended cut-offs for Digit
      Span indicators (Vocabulary Minus Digit Span and four-digit forward span time
      score) provided > or =90% specificity across participants, while the majority of
      other effort tests displayed specificities in the 30-70% range. Analyses of test
      specificity as a function of Mini Mental Status Examination (MMSE) score and
      specific dementia diagnosis are provided, as well as adjustments to cut-offs to
      maintain specificity where feasible.

PMID- 18609333
TI  - Effects of parental presence and child characteristics on children's
      neuropsychological test performance: third party observer effect confirmed.
AB  - An observer's presence during neuropsychological testing can impair task
      performance in adults, but this phenomenon has yet to be examined as it pertains
      to neuropsychological testing of children. The current study focused on parental
      presence effects on nonverbal intelligence and verbal learning performance of
      children aged 6 to 8 years. Each of 53 children completed one form of the Test of
      Nonverbal Intelligence-3rd Edition (TONI-3) and the Selective Reminding Test
      (SRT) with his/her parent in the room and an alternate form of each with only the
      experimenter with the child in the testing room. Of several possible covariates,
      only the child's age was significant and included in final analyses. Using a
      doubly multivariate MANCOVA it was discovered that parent's observation status
      significantly interacted with the order of observation to impact task
      performance. This significant effect can mainly be attributed to a steeper
      positive slope (i.e., children's greater improvement over time) for TONI-3 T
      scores in children whose parent observed first; children whose parents were
      absent for the first half of testing improved to a lesser extent over time. No
      significant relationship was found between observation and SRT scores. These
      results lend some support to the assertion of previous studies that the presence
      of third party observers may affect the validity of neuropsychological test
      results.

PMID- 18609334
TI  - Spontaneous intracranial hypotension masquerading as frontotemporal dementia.
AB  - F.D. exhibited the cognitive and behavioral profile of frontotemporal dementia in
      the context of spontaneous intracranial hypotension (SIH). Symptoms included
      orthostatic headache, as well as cognitive and personality changes. He underwent
      CT, EEG, and MRI as well as neuropsychological evaluations before and after
      corticosteroid treatment. The initial evaluation documented significant cognitive
      impairment with a predominance of executive dysfunction. Following treatment, a
      second evaluation revealed marked improvement in cognition and behavior. Rapid
      diagnosis and treatment can yield a favorable outcome. Both quantitative and
      qualitative information from measures of executive functioning were discussed, as
      well as their anatomical substrates.

PMID- 18609335
TI  - Percentiles please: the case for expressing neuropsychological test scores and
      accompanying confidence limits as percentile ranks.
AB  - Many commentators on neuropsychological assessment stress the disadvantages of
      expressing test scores in the form of percentile ranks. As a result, there is a
      danger of losing sight of the fundamentals: percentile ranks express scores in a
      form that is of greater relevance to the neuropsychologist than any alternative
      metric because they tell us directly how common or uncommon such scores are in
      the normative population. We advocate that, in addition to expressing scores on a
      standard metric, neuropsychologists should also routinely record the percentile
      rank of all test scores so that the latter are available when attempting to reach
      a formulation. In addition, it is argued that the current practice of expressing
      confidence limits on test scores on a standard score metric should be
      supplemented with confidence limits expressed as percentile ranks, because the
      latter provide a more direct and tangible indication of the uncertainty
      surrounding an observed score. Computer programs accompany this paper and can be
      used to obtain percentile rank confidence limits for Index scores (and FSIQs) on
      the WAIS-III or WISC-IV (these can be downloaded from the following web page:
      http://www.abdn.ac.uk/~psy086/dept/PRCLME.htm).

PMID- 18609336
TI  - A short version of Rao's Brief Repeatable Battery as a screening tool for
      cognitive impairment in multiple sclerosis.
AB  - Rao's Brief Repeatable Battery (BRB) is the most widely used instrument for
      cognitive evaluation in multiple sclerosis (MS). We assessed a short version of
      the BRB in 116 relapsing-remitting participants. We found that the administration
      of three tests, the Selective Reminding Test, the Paced Auditory Serial Addition
      Test-3 seconds and the Symbol Digit Modalities Test, was able to detect cognitive
      impairment with a sensitivity of 94%, a specificity of 84%, and an accuracy of
      89%. On the basis of these results we developed a screening algorithm requiring 5
      to 15 minutes, which may represent a highly sensitive and rapid tool to detect MS
      associated cognitive impairment.

PMID- 18609338
TI  - Clinical myths of forensic neuropsychology.
AB  - Clinical myths and lore are unfounded beliefs that still influence practice
      decisions. I examine the validity of six beliefs commonly encountered in forensic
      neuropsychology practice: the admissibility of test batteries; avoidance of
      practice effects; forewarning insures good effort; average deficits in bright
      persons; 15% chronic impairment in mild brain injury; and examiner bias causing
      malingering. I show these beliefs are invalid because of material
      misunderstandings of case law and literature, falsification by empirical
      findings, and lack of authoritative sources. The benefits, costs, and persistence
      of clinical myths are discussed.

PMID- 18609337
TI  - Neuropsychological performance in advanced age: influences of demographic factors
      and Apolipoprotein E: findings from the Cache County Memory Study.
AB  - The Cache County Study of Memory in Aging (CCMS) is an epidemiological study of
      Alzheimer's disease (AD), mild cognitive disorders, and aging in a population of
      exceptionally long-lived individuals (7th to 11th decade). Observation of
      population members without dementia provides an opportunity for establishing the
      range of normal neurocognitive performance in a representative sample of the very
      old. We examined neurocognitive performance of the normal participants undergoing
      full clinical evaluations (n = 507) and we tested the potential modifying effects
      of apolipoprotein E (APOE) genotype, a known genetic risk factor for the later
      development of AD. The results indicate that advanced age and low education are
      related to lower test scores across nearly all of the neurocognitive measures.
      Gender and APOE epsilon4 both had negligible and inconsistent influences,
      affecting only isolated measures of memory and expressive speech (in case of
      gender). The gender and APOE effects disappeared once age and education were
      controlled. The study of this exceptionally long-lived population provides useful
      normative information regarding the broad range of "normal" cognition seen in
      advanced age. Among elderly without dementia or other cognitive impairment, APOE
      does not appear to exert any major effects on cognition once other demographic
      influences are controlled.

PMID- 18609339
TI  - Malingering Scales for the Continuous Recognition Memory Test and the Continuous
      Visual Memory Test.
AB  - Continuous Visual Memory Test (CVMT) and Continuous Recognition Memory Test (CRM)
      scores of 24 litigants with definite malingered neurocognitive dysfunction
      (definite MND) were contrasted with those of 27 patients with moderate (n = 12)
      and severe (n = 15) traumatic brain injury (TBI). Analysis with chi-square
      identified 20 CVMT and 33 CRM items that discriminated the definite MND from TBI
      cases. Receiver operating characteristic (ROC) area under curve (AUC) was 0.918
      for the CVMT scale, and 0.962 for the CRM scale, p = 0.184. Cutting scores were
      derived yielding sensitivity and specificity of 0.83 and 0.889 for the 20-item
      CVMT scale, and 0.875 and 0.93 for the 33-item CRM scale. On cross-validation
      contrasting performance of 17 litigants with evidence of probable MND and non
      litigating psychiatric (n = 14) and neurologic (n = 13) patients, ROC AUC was
      0.779 for the CVMT scale, and 0.847 for the CRM scale, p = 0.447. Sensitivity and
      specificity were 0.35 and 0.93 for the CVMT, and 0.529 and 0.96 for the CRM,
      using the cutting scores from the derivation sample. ROC AUC differences
      contrasting values for the definite MND/TBI comparison to the probable
      MND/neurologic and psychiatric comparison approached significance for the CRM SVT
      scale (p = 0.059), and for the CVMT SVT scale (p = 0.082). These data suggest
      that the malingering scales for the CVMT and CRM are more sensitive to definite
      rather than probable MND, and these scales are better at ruling in than ruling
      out malingered visual memory deficits.

PMID- 18609340
TI  - Effect of the subdermal contraceptive etonogestrel implant (Implanon) on
      biochemical and hormonal parameters (three years follow-up).
AB  - OBJECTIVE: To determine whether the use of the subdermal contraceptive implant
      releasing etonogestrel (Implanon) affects serum hormonal and biochemical indices.
      METHODS: Seventy women with a mean age of 28.5+/-3.4 years were enrolled into
      this prospective observational study. After placement of an Implanon rod, they
      were followed-up for three years. Baseline and end-of-study values of serum low
      density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol,
      triglycerides, fasting glucose, blood urea nitrogen (BUN), creatinine, SGOT,
      SGPT, follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol,
      free 3,5,3'-tri-iodothyronine (fT3), free thyroxine (fT4), thyroid stimulating
      hormone (TSH), and prolactine (PRL) were compared using Student's t-test.
      RESULTS: There was no failure of contraception during the three year period. No
      statistically significant differences were observed between the initial and final
      levels of fasting blood glucose, BUN, SGOT, SGPT, LDL, HDL, E2, FSH, LH, fT3, fT4
      and TSH (p>0.05), but the increase in PRL, cholesterol and triglycerides, and the
      decrease in creatinine levels at the end of three years were statistically
      significant (p<0.05) although the values were still within normal ranges.
      CONCLUSION: Our findings confirm data from the literature according to which
      Implanon does not affect meaningfully reproductive hormonal parameters, thyroid
      function, hepatic and renal functions, and glucose metabolism. However, further
      studies are needed to elucidate lipid metabolism changes.

PMID- 18609341
TI  - Potentially harmful traditional practices during pregnancy and postpartum.
AB  - OBJECTIVES: Culturally embedded attitudes and beliefs affect people's lifestyle
      and health. Traditional practices such as bathing the baby in salt water to
      prevent him from smelling bad, regarding pregnancy as a shameful situation, and
      concealing pregnancy, may cause harm. This descriptive study aimed at identifying
      potentially harmful practices of married women during pregnancy, delivery and
      postpartum, in Turkey. METHODS: The sample studied consisted of 121 women. A
      questionnaire was used to gather information during face-to-face interviews.
      RESULTS: Eighty percent of the respondents were literate/primary school
      graduates, 45% had given birth at home. The most potentially harmful practices
      among women were swaddling (81%), dressing the baby with a sand-filled nappy
      ('holluk') (35%), and bathing the baby in salt water (40%). A relationship
      between traditional postpartum practices and demographic characteristics of women
      such as age, educational status, age at marriage and birth place was observed
      (p<0.05). CONCLUSIONS: Turkish women still carry out certain traditional
      practices during and after pregnancy, some of which adversely affect them or
      their babies. It is important to gain an understanding of these potentially
      harmful customs and cultural beliefs so that health education programmes can be
      implemented that dissuade women from resorting to these practices.

PMID- 18609342
TI  - Quality of life and sexual functioning of Polish infertile couples.
AB  - OBJECTIVES: To evaluate the influence of infertility on the quality of life (QoL)
      and sexual functioning of infertile couples. METHODS: The research group
      consisted of 206 infertile couples and the control group of 190 fertile couples.
      A specific questionnaire was used as a research tool. It gathered information
      about socio-demographic features and infertility status, and included validated
      scales: Short Form-36 Health Survey, Female Sexual Function Index and
      International Index of Erectile Function. RESULTS: The QoL parameters in all
      categories were generally lower for infertile women than for those of the control
      group. Clinical sexual dysfunctions were not significantly more common among
      infertile than fertile women (17.5% versus 12.1%, p=0.13). Clinically relevant
      erectile dysfunctions were diagnosed in 23.9% of infertile men and in 13.7% of
      the controls. Male infertility had the most significant negative effect on men's
      sexual functioning. CONCLUSIONS: The risk groups for decreased QoL are infertile
      women and older subjects with lower education and occupationally inactive.
      Clinically relevant sexual disorders in the infertile population most frequently
      affect older men, with a lower educational level and with previously diagnosed
      male infertility.

PMID- 18609343
TI  - Usage of Long Acting Reversible Contraceptive Methods (LARC) in couples attending
      for vasectomy counselling.
AB  - OBJECTIVE: Vasectomy is a safe and effective method of permanent contraception. A
      proportion of men will regret the procedure and some may experience chronic
      testicular pain. National recommendations in the UK advocate that couples
      requesting sterilization should be counselled and given access to Long Acting
      Reversible Contraceptive (LARC) methods. This study aims to ascertain usage of
      LARC methods in couples attending for vasectomy counselling. METHOD: A case notes
      review of 200 consecutive couples attending for vasectomy counselling between
      January and May 2006. RESULTS: Most couples were using condoms for contraception
      (51%) prior to vasectomy counselling. Only 11% of couples were using a LARC and
      25% of couples had ever used one. The copper intrauterine device was the most
      popular LARC with 16% having ever used it; hormonal LARCs were unpopular. Some
      couples (9.5%) expressed dissatisfaction with current methods and associated
      health risks. CONCLUSION: Usage of LARC methods was low but similar to that of
      the background population in the UK. Couples attending for vasectomy are seeking
      effective contraception but prefer non-hormonal methods. LARC uptake in the UK is
      poor; there is a need for wider education and awareness of all LARC methods
      including side effects and safety.

PMID- 18609344
TI  - Assessing female condom acceptability among heterosexual Spanish couples.
AB  - OBJECTIVE: To assess the acceptability of the female condom in a sample of young
      heterosexual Spanish couples. METHODS: The sample was made up of 45 couples (90
      participants) from Spain. The age range was from 19 to 42 years. The study was
      carried out in three stages: pre-trial, post-trial, and follow-up (one year
      later). RESULTS: Before the intervention, 88 participants (97.8%) had heard about
      the female condom, although 73 participants (81.2%) claimed to know very little
      about the method, and barely one-third had seen one. The appraisals after the
      trial period reveal differing levels of satisfaction with the method, with no
      significant differences found by gender. Those participants who used a greater
      number of condoms during the trial period pointed out more positive points about
      the method, but also more negative points. Of the 17 couples who continued to
      participate in the follow-up stage (one year after the trial stage), only one
      (5.9%) still used the female condom. However, 10 men (58.8%) and 8 women (47.1%)
      expressed a willingness to use it in the future, and 12 women (70.6%) and 11 men
      (64.7%) had told friends and acquaintances about it. CONCLUSION: This study
      reveals that although the female condom is considered to be a useful method, it
      is still largely unknown and requires further promotion if it is to be used by
      young couples.

PMID- 18609345
TI  - Maternal employment and maternity care in Al-Hassa, Saudi Arabia.
AB  - OBJECTIVE: To examine the effects of women employment on maternity care and
      pregnancy outcome in Al-Hassa, Saudi Arabia. STUDY DESIGN: Two groups of highly
      educated employed (144 teachers and health care workers) and 162 non-employed
      mothers, all of Saudi nationality, were compared. Data were collected from family
      files kept at primary health care centres as well as by direct interview with
      mothers, two months after delivery. RESULTS: Working mothers initiated care late
      in pregnancy and subsequently attended fewer visits. They had more caesarean
      sections, preterm deliveries and low birth weight infants in the index pregnancy.
      These adverse effects were more prominent with unfavourable working conditions.
      CONCLUSION: Maternal employment, especially with unfavourable working conditions,
      is associated with inadequate antenatal care and poorer pregnancy outcome,
      compared to housewives of the same high educational level. Maternity care
      providers need training in occupational medicine to promote the health of working
      mothers.

PMID- 18609346
TI  - The levonorgestrel intrauterine system (Mirena) for treatment of idiopathic
      menorrhagia. Assessment of quality of life and satisfaction.
AB  - OBJECTIVES: To evaluate patient satisfaction and improvement in quality of life
      (QoL) among women with idiopathic menorrhagia treated with the levonorgestrel
      intrauterine system (LNG-IUS). STUDY DESIGN: Prospective-observational study with
      one-year follow-up in which 225 women were enrolled who had a LNG-IUS inserted
      for control of idiopathic menorrhagia. Bleeding, tolerability, user satisfaction,
      and health-related QoL (by means of the SF-36 QoL questionnaire) were assessed.
      RESULTS: There was a statistically significant reduction in the amount of
      bleeding, an increase of haemoglobin and ferritin levels, and an improved QoL
      score. A high degree of satisfaction was reported by over 98% of patients.
      CONCLUSIONS: The LNG-IUS is an effective and well-tolerated treatment modality in
      idiopathic menorrhagia. The QoL of women treated with the LNG-IUS is markedly
      improved, causing high levels of patient satisfaction. This IUS can be regarded
      as a first-choice therapy in idiopathic menorrhagia.

PMID- 18609347
TI  - Pregnancy-preserving myomectomy: preliminary report on a new surgical technique.
AB  - Uterine myomas are found in 0.3-2.6% of pregnant women. In one case out of ten
      they cause complications. Treatment is primarily conservative but in cases of
      failure, surgery cannot be avoided. We present a case of a pregnant woman with
      myomas. Because of failure of conservative management and severe abdominal pain,
      we performed a myomectomy at 18 weeks' gestation with preservation of the
      pregnancy. We describe a modified surgical technique whereby interrupted sutures
      are first placed around the myoma for haemostasis. We achieved good pregnancy
      outcome by caesarean section carried out near term. Incidence, presentation, and
      challenges associated with the management of myomas during pregnancy are briefly
      discussed.

PMID- 18609348
TI  - The impact of health education on attitudes towards female genital mutilation
      (FGM) in a rural Nigerian community.
AB  - OBJECTIVES: To determine the level of practice of female genital mutilation (FGM)
      and the impact of a health education intervention in Shao community. MATERIALS
      AND METHODS: Intervention study using a multistage sampling technique. The
      instrument was a pre-tested, structured questionnaire. The survey was
      supplemented by an in-depth interview of the traditional excisors. RESULTS: Most
      respondents (88.0%) cited traditional excisors as operators of the procedure,
      while 7.8% mentioned health workers. Factors found to be statistically
      significantly associated with the practice of FGM are age, gender and educational
      status of respondents (p<0.05). The age at which FGM is usually performed was put
      at under one year old by 60.3% of respondents. All respondents cited type II FGM
      as the type practised in the community. Most (88.0%) of the female respondents
      were excised. A greater proportion of men than women did not want the practice of
      FGM stopped in the pre-intervention stage; however, there was a statistically
      significant decrease in the proportion of males who did not want the practice of
      FGM stopped in the post-intervention stage. Also, there was a statistically
      significant increase in the proportion of respondents who had no intention to
      excise future female children in the post-intervention stage (p<0.05).
      Legislation, female literacy and empowerment, educating men and provision of
      alternative vocation for excisors were means suggested by respondents for
      stopping the practice. CONCLUSION AND RECOMMENDATIONS: The health education
      intervention had a positive impact on the attitude of respondents towards FGM.
      However, for sustainable behavioural changes that will lead to elimination of FGM
      practice, we recommend placing FGM elimination efforts within a comprehensive
      development strategy and the larger context of reproductive health and gender
      education in Nigeria.

PMID- 18609349
TI  - Funding of vocational training programmes for general  practice/family medicine
      in Europe.
AB  - BACKGROUND/OBJECTIVE: As financial arrangements for vocational training (VT) in
      general practice/family medicine seemed to differ among European countries, the
      VT committee of EURACT compiled an overview to permit comparison. METHODS: A
      questionnaire with open and closed questions was e-mailed in March 2006 to
      representatives of the 34 different countries on the EURACT Council. RESULTS:
      Thirty completed questionnaires were returned (88% response rate). The salary of
      the GP trainee during clinical training in GP/FM is paid by the state on its own
      or with others in 19 countries (63%), and is the same during community and
      hospital rotations in 22 countries (73%). The GP trainer gets extra payment for
      supervision and teaching in only 14 countries (47%). Structured VT programmes are
      fully or partly financed by the state in 17 countries (57%), with trainees being
      paid for working hours spent in seminars/coursework in 19 countries (63%).
      Funding was cited as the commonest challenge and strength regarding VT programmes
      (cited 20 and 11 times, respectively). CONCLUSION: Recommendations made regarding
      the provision of vocational training across Europe include a structured
      curriculum supported by adequate funding, the professional recognition of GP
      trainers, which includes a fair and appropriate salary, and equity of salary for
      GP trainees.

PMID- 18609350
TI  - Acute fatty liver of pregnancy and molecular absorbent recirculating system
      (MARS)-therapy: a case report.

PMID- 18609351
TI  - Outcomes of preterm premature rupture of membranes in twin pregnancies.
AB  - OBJECTIVE: To describe outcomes in twin pregnancies with preterm premature
      rupture of membranes (PPROM). METHODS: Dichorionic twin pregnancies complicated
      by PPROM at <34 weeks of gestation for the period 2003 to 2006 were identified.
      Outcomes were obtained through chart review. The relationship between gestational
      age at premature rupture of membranes (PROM), latency from PROM to delivery, and
      infection were examined. RESULTS: In 49 twin pregnancies, the median gestational
      age at PROM was 31 weeks with a median latency between PROM and delivery of 0
      days (interquartile range 0-6). Latency intervals of >or=2 and >or=7 days were
      achieved by 40.8% and 22.4%, respectively. PPROM at <30 weeks was associated with
      significantly higher rates of latency of >or= 2 days (70.6% vs. 25.0%) and >or=7
      days (47.1% vs. 9.4%). There was a significant relationship between latency and
      clinical and histologic signs of infection. CONCLUSIONS: After 30 weeks, most
      twin pregnancies with PPROM delivered within 2 days. Infection appears to be a
      consequence rather than a cause of PPROM in most cases.

PMID- 18609352
TI  - Perinatal outcomes during 1986-2005 in Tuzla Canton, Bosnia and Herzegovina.
AB  - AIM: To determine the incidence rate and causes of perinatal mortality and make a
      comparison between the incidence rate and causes of perinatal mortality in the
      prewar (1986-1991), war (1992-1995) and postwar (1996-2005) periods in Tuzla
      Canton, Bosnia and Herzegovina. METHODS: We retrospectively collected data from
      the databases of University Department for Gynecology and Obstetrics Tuzla. Data
      on the number of live births, stillbirths, early neonatal deaths, causes of
      death, gestational age and birth weights were collected. RESULTS: There were
      101712 deliveries all together in the above mentioned period, out of which 101638
      resulted in liveborn children. Perinatal mortality gradually declines in the
      period of 1986-2000. The decline owns mostly to early neonatal mortality more
      than to fetal which also shows the trend of decrease. Statistically significant
      difference in perinatal mortality was found between period 2001-2005 and another
      analysed periods, and the most difference was found between 1991-1995 and 1996
      2000 (p < 0.01). Statistically significant difference in fetal mortality was
      found between period 2001-2005 and 1986-1990. Statistically significant
      difference in early neonatal mortality was found between period 2001-2005 and
      1986-1990 (p = 0.005; p < 0.005). CONCLUSION: Perinatal mortality in Tuzla Canton
      were significant higher during the war, mainly due to lower adequacy and
      accessibility of perinatal health care. During the peace period a significant
      decline of perinatal mortality is registered, due to early neonatal death.

PMID- 18609353
TI  - The effect of epidural analgesia on labor progress and outcome in nulliparous
      women.
AB  - OBJECTIVE: The present study was designed to investigate the influence of
      epidural analgesia on labor progress and outcome in nulliparous women. METHODS: A
      population-based study comparing women with and without epidural analgesia was
      conducted. Deliveries occurred during 1988-2006 at the Soroka University Medical
      Center. A multivariable logistic regression model with backward elimination was
      constructed to control for confounders. RESULTS: During the study period there
      were 39 498 deliveries; epidural analgesia was given in 9960 (25.2%) of these.
      Using a multivariable analysis with backward elimination, the following
      conditions were significantly associated with the use of epidural analgesia:
      advanced maternal age, oligohydramnios, premature rupture of membranes, induction
      of labor, and Jewish (vs. Bedouin) ethnicity. These patients were more likely to
      deliver by cesarean delivery (CD; OR = 1.4, 95% CI 1.3-1.5; p < 0.001) and vacuum
      extraction (OR = 1.5, 95% CI 1.4-1.7; p < 0.001). After controlling for possible
      confounders such as macrosomia, failed induction, hypertensive disorders,
      gestational diabetes, maternal age, labor dystocia, and ethnicity, epidural
      analgesia was not found to be an independent risk factor for CD but rather a
      protective factor (OR = 0.9, 95% CI 0.8-0.9; p = 0.038). When vacuum extraction
      was the outcome variable, epidural analgesia was documented as an independent
      risk factor (OR = 1.1, 95% CI 1.01-1.3; p = 0.04). CONCLUSIONS: Epidural
      analgesia in nulliparous parturients increases the risk for labor dystocia and
      accordingly is an independent risk factor for vacuum extraction. Nevertheless, it
      does not pose an independent risk for cesarean delivery.

PMID- 18609354
TI  - Variation in the postpartum hemorrhage rate in a clinical trial of oral
      misoprostol.
AB  - OBJECTIVE: The main objective of this study was to identify factors associated
      with variation in the rate of acute postpartum hemorrhage (PPH), defined as blood
      loss >or= 500 mL within 2 hours of delivery, observed in a randomized clinical
      trial of misoprostol for the prevention of PPH, conducted in rural India.
      Although the women in the misoprostol group had a significantly lower probability
      of having a PPH, we also noted a reduction in the rate of PPH in the placebo
      group over the course of the study. We hypothesized that this was due to the
      changing skills of the auxiliary nurse midwives (ANMs) over the course of the
      study. METHODS: We conducted a post-hoc analysis examining variation in PPH rates
      over the duration of the trial among the women randomized to the placebo arm (n =
      808). Descriptive, correlation analysis and generalized estimating equations
      (GEE) were used to predict PPH rates. With no direct measure of ANM skills, we
      used proxy measures, including: (1) the ANM's point of entry into the study
      (original ANMs at the initiation of the trial were less skilled than replacement
      ANMs); (2) the study duration, representing exposure of the ANM to ongoing
      training and monitoring; and (3) duration of the second stage of labor as a
      measure of improved delivery practices. RESULTS: As the study duration increased,
      the duration of the second stage of labor decreased (-0.12, p = 0.001) and as the
      duration of the second stage of labor decreased, the rate of PPH decreased
      (0.0282; 95% CI 0.0201-0.0363). For each 10-minute increase in the duration of
      second stage labor increased PPH odds by 7.1% and each 30-day duration of the
      trial decreased PPH odds by 3.4%. Additionally, a patient delivered by an
      original ANM was 3.14 times more likely to have a PPH compared to a patient
      delivered by a replacement ANM. CONCLUSIONS: Declining PPH rates were associated
      with improved skills and delivery practices that decreased duration of the second
      stage of labor. These improvements appeared to be consistent with the
      introduction of the more skilled replacement ANMs as well as ongoing training and
      monitoring for all ANMs over the duration of the trial.

PMID- 18609355
TI  - Prenatal ultrasonographic diagnosis of abdominal cystic lymphangioma: a case
      report.
AB  - Abdominal lymphangioma is a rare tumor of the lymphatic vessels. A case of an
      abdominal cystic lymphangioma identified at 22 weeks of gestation is reported.
      Ultrasonographic monitoring showed a progressive increase of mass size during the
      gestation. Pregnancy was terminated at 38 weeks and the newborn was submitted to
      a laparotomy with resection of all cystic structures. At the present time the
      infant is three years old and is doing well.

PMID- 18609356
TI  - Post-cesarean adhesions--are they a unique entity?
AB  - OBJECTIVE: The connection between adhesions and post-operative symptoms is well
      established. Adhesions are found in nearly half of the women at the time of their
      repeat cesarean section. For the first time a prospective pilot study has been
      done in order to evaluate the clinical significance of post-cesarean adhesions.
      STUDY DESIGN: Fifty women who underwent cesarean section in their first pregnancy
      were interviewed prior to their repeat operation regarding their symptoms after
      the first surgery. The clinical history was correlated with the findings during
      the second intervention. RESULTS: No correlation was found between the clinical
      symptoms and the operative findings regarding abdominal pains, urinary symptoms,
      dyspareunia, or dysmenorrhea. Surprisingly, although non-significant, women with
      adhesions reported fewer postoperative gastrointestinal symptoms than the women
      with no adhesions. CONCLUSION: More studies will have to been done, but the
      analysis of this pilot study supports the hypothesis that adhesions following
      cesarean section are a unique entity.

PMID- 18609357
TI  - Release of inositol phosphoglycan P-type by the human placenta following insulin
      stimulus: a multiple comparison between preeclampsia, intrauterine growth
      restriction, and gestational hypertension.
AB  - OBJECTIVE: Abnormal metabolism of inositol phosphoglycan P-type (P-IPG) has been
      described in insulin-resistant states. Recently, a definite link between P-IPG
      and preeclampsia has been reported. P-IPG release after insulin stimulus has been
      described in the placental tissue of healthy women and a complete absence of P
      IPG release has been found in preeclamptic samples, associated with disturbed
      insulin signaling. This study was undertaken to assess the release of this
      mediator in intrauterine growth restriction (IUGR) and hypertensive disorders
      other than preeclampsia. METHODS: Seven women with IUGR, seven with gestational
      hypertension, 11 with preeclampsia, and 12 controls were recruited for this
      study. Fresh placental membranes were prepared and incubated with human
      recombinant insulin. Bioactivity of P-IPG released after insulin stimulus was
      assessed using a specific bioassay. A multiple comparison between groups was
      carried out. The study population provided a statistical power of 0.94. RESULTS:
      P-IPG release was highest and lowest from healthy and preeclamptic samples,
      respectively (p < 0.01). Specimens from patients with IUGR and gestational
      hypertension released less P-IPG than did controls (p < 0.05). CONCLUSIONS:
      Abnormal release of P-IPG from placentas of IUGR and gestational hypertensive
      mothers seems to confirm an association between these disorders of human
      pregnancy and insulin resistance.

PMID- 18609358
TI  - Management of a massive pulmonary embolism in a pregnant patient with mechanical
      fragmentation followed by delayed catheter-directed thrombolysis in the early
      postpartum period.
AB  - There are limited data available on the management of massive pulmonary embolism
      in pregnancy. The use of systemic thrombolysis has been reported, but there are
      few documented cases on the use of mechanical fragmentation or catheter-directed
      thrombolysis. Systemic thrombolysis in pregnancy increases the risk of major
      hemorrhage and there are reports of massive subchorionic hematomas following its
      use. We describe the use of mechanical fragmentation and optional retrievable
      inferior vena cava (IVC) filter insertion in a 38-week pregnant woman followed by
      delayed pharmacological catheter-directed thrombolysis during the early
      postpartum period to successfully treat a massive pulmonary embolism.

PMID- 18609359
TI  - Amniocentesis in the management of preterm premature rupture of the membranes: a
      retrospective cohort analysis.
AB  - OBJECTIVE: This retrospective analysis determined the utility of amniocentesis in
      the management of preterm premature rupture of the membranes (PPROM). STUDY
      DESIGN: Consecutive patients with PPROM were managed with and without
      amniocentesis. Both groups received antibiotics and corticosteroids; tocolytics
      were withheld. Patients were induced if clinical or amniotic fluid (AF) proven
      chorioamnionitis occurred or gestational age goals were reached. Primary
      endpoints were individual and composite neonatal morbidity (CNM). RESULTS: One
      hundred forty-seven maternal patients were managed with amniocentesis (AC) and
      146 were managed without amniocentesis (NAC). CNM was significantly reduced in
      the group managed with AC (OR 2.94, 95% CI 1.68-5.15, NAC vs. AC). NAC patients
      had similar rates of neonatal sepsis as well as CNM to those patients in the AC
      group with positive AF Gram stains and/or cultures. CONCLUSIONS: Patients with
      PPROM who are managed with AC have significantly less CNM than NAC patients.

PMID- 18609360
TI  - Differential effects of betamethasone on the fetus between morning and afternoon
      recordings.
AB  - BACKGROUND: Fetal heart rate (FHR) variation and fetal movements show a diurnal
      rhythm, a rise in the afternoon and evening compared to morning hours. A previous
      study showed that reductions in fetal parameters occurring two to three days
      after betamethasone administration are most likely caused by suppression of the
      normal rise during the day. Therefore monitoring during the morning could
      circumvent the suppressive effects of betamethasone. OBJECTIVE: To study the
      effects of betamethasone on fetal diurnal rhythms, by comparing morning and
      afternoon recordings over five successive days. METHODS: This was a prospective
      longitudinal study of 20 women at 25-34 weeks of gestation. One-hour recordings
      of FHR and fetal movements were made on each of five successive days in the
      morning and afternoon. Betamethasone was administered on day 0 and day 1.
      RESULTS: We found no reduction of FHR variation on days 2 and 3 in the morning.
      In contrast, in the afternoon a reduction of FHR variation occurred on day 2.
      Time courses of fetal body and breathing movements during the morning were not
      affected by betamethasone administration. CONCLUSIONS: Transient reductions in
      fetal movement and FHR variation after glucocorticoid administration are not
      observed in the morning. For fetal monitoring and especially for assessing trends
      in fetal heart rate variation and movements with time, morning recordings should
      be preferably used in the period around glucocorticoid administration.

PMID- 18609361
TI  - The anti-inflammatory limb of the immune response in preterm labor, intra
      amniotic infection/inflammation, and spontaneous parturition at term: a role for
      interleukin-10.
AB  - OBJECTIVE: The anti-inflammatory limb of the immune response is crucial for
      dampening inflammation. Spontaneous parturition at term and preterm labor (PTL)
      are mediated by inflammation in the cervix, membranes, and myometrium. This study
      focuses on the changes in the amniotic fluid concentrations of the anti
      inflammatory cytokine interleukin (IL)- 10. The objectives of this study were to
      determine whether there is a relationship between amniotic fluid concentrations
      of IL-10 and gestational age, parturition (at term and preterm), and intra
      amniotic infection/inflammation (IAI). STUDY DESIGN: A cross-sectional study was
      conducted including 301 pregnant women in the following groups: (1) mid-trimester
      of pregnancy who delivered at term (n = 112); (2) mid-trimester who delivered
      preterm neonates (n = 30); (3) term not in labor without IAI (n = 40); (4) term
      in labor without IAI (n = 24); (5) term in labor with IAI (n = 20); (6) PTL
      without IAI who delivered at term (n = 31); (7) PTL without IAI who delivered
      preterm (n = 30); (8) PTL with IAI who delivered preterm (n = 14). IL-10
      concentrations in amniotic fluid were determined by a specific and sensitive
      immunoassay. Non-parametric statistics were used for analysis. RESULTS: (1) IL-10
      was detectable in amniotic fluid and its median concentration did not change with
      gestational age from mid-trimester to term. (2) Patients in labor at term had a
      significantly higher median amniotic fluid IL-10 concentration than that of
      patients at term not in labor (p = 0.04). (3) Women at term in labor with IAI had
      a significantly higher median amniotic fluid IL-10 concentration than that of
      patients at term in labor without IAI (p = 0.02). (4) Women with PTL and IAI who
      delivered preterm had a significantly higher median amniotic fluid concentration
      of IL-10 than those without IAI who delivered preterm and than those who
      delivered at term (p = 0.009 and p < 0.001, respectively). (5) Among patients
      with preterm labor without IAI, those who delivered preterm had a significantly
      higher median amniotic fluid IL-10 concentration than those who delivered at term
      (p = 0.03). CONCLUSIONS: The anti-inflammatory cytokine IL-10 is detectable in
      the amniotic fluid of normal pregnant women. Spontaneous parturition at term and
      in preterm gestation is associated with increased amniotic fluid concentrations
      of IL-10. IAI (preterm and at term) is also associated with increased amniotic
      fluid concentrations of IL-10. We propose that IL-10 has a role in the regulation
      of the immune response in vivo by initiating actions that dampen inflammation.

PMID- 18609362
TI  - Effect of fetal diagnosis on the outcomes of second-trimester pregnancy
      termination for fetal abnormalities: a pilot study.
AB  - OBJECTIVE: To explore whether the outcomes of second-trimester pregnancy
      termination for fetal abnormalities are affected by fetal diagnoses. METHODS:
      This was a retrospective review of cases undergoing second-trimester pregnancy
      termination for the fetal diagnoses of hemoglobin Barts, trisomy 21, and trisomy
      18 during the period from 1999 to 2006. The affected pregnancies were terminated
      by vaginal misoprostol. The outcome measures were: (1) abortion within 24 hours
      after misoprostol commencement, (2) histology-confirmed incomplete abortion, and
      (3) experience of significant side effects during termination (temperature over
      39 degrees C or need for metoclopramide for vomiting). RESULTS: One hundred and
      twenty cases were available for analysis. After adjusting for maternal age,
      parity, history of cesarean delivery, body mass index, gestation, and fetal
      hydrops, pregnancy termination for trisomy 21 was associated with a higher risk
      of incomplete abortion than trisomy 18 and hemoglobin Barts (odds ratio 5.25, 95%
      confidence interval 1.24-22.19, p = 0.024). The chance of abortion within 24
      hours and experience of significant side effects were not found to be associated
      with fetal diagnosis. CONCLUSIONS: Pregnancy termination for trisomy 21 is
      associated with a higher risk of incomplete abortion. Fetal diagnosis affects the
      outcome of pregnancy termination.

PMID- 18609363
TI  - Orthographic congruency effects in the suprasegmental domain: evidence from Thai.
AB  - The influence of orthographic knowledge on lexical tone processing was examined
      by manipulating the congruency between the tone and the tone marker of Thai
      monosyllabic words presented in three metalinguistic tasks. In tone monitoring
      (Experiment 1) and same-different tone judgement (Experiment 2)--that is, tasks
      that require an explicit analysis of tone information---an orthographic
      congruency effect was observed: Better performance was found when both tone and
      tone marker led to the same response than when they led to opposite, competing
      responses. In rhyme judgement (Experiment 3), a metaphonological task that allows
      tone to be processed in a more natural way since it does not require explicit
      analysis of tone, the orthographic effect emerged only when the interstimulus
      interval was lengthened from 30 to 1,200 ms. In addition to demonstrating the
      generalization of the orthographic congruency effect to the suprasegmental domain
      in Thai, the present data also suggest relatively late and task-dependent
      activation of orthographic representations of tone.

PMID- 18609364
TI  - The role of meaning in contextual cueing: evidence from chess expertise.
AB  - In contextual cueing, the position of a search target is learned over repeated
      exposures to a visual display. The strength of this effect varies across stimulus
      types. For example, real-world scene contexts give rise to larger search benefits
      than contexts composed of letters or shapes. We investigated whether such
      differences in learning can be at least partially explained by the degree of
      semantic meaning associated with a context independently of the nature of the
      visual information available (which also varies across stimulus types). Chess
      boards served as the learning context as their meaningfulness depends on the
      observer's knowledge of the game. In Experiment 1, boards depicted actual game
      play, and search benefits for repeated boards were 4 times greater for experts
      than for novices. In Experiment 2, search benefits among experts were halved when
      less meaningful randomly generated boards were used. Thus, stimulus
      meaningfulness independently contributes to learning context-target associations.

PMID- 18609366
TI  - Within-subject renewal in sign tracking.
AB  - Three sign-tracking experiments using pigeon subjects examined the contextual
      dependence of extinction after conditioning. Renewal of extinguished responding
      occurred when testing occurred in a different context, using a variety of
      different renewal designs. In each case, a within-subject design ensured that the
      various contexts were equivalent in their general treatment histories and
      differed only in whether or not a particular stimulus had been extinguished in
      their presence. These results strengthen the view that extinction is relatively
      context specific.

PMID- 18609367
TI  - Priming of abstract letter identities in the letter match task.
AB  - Previous studies of letter recognition have not found priming for abstract letter
      identities. We used a task that required participants to decide whether a target
      is the same or different from a reference letter presented in opposite case,
      which avoids the shortcomings of tasks used in previous studies. We found robust
      priming effects in this task, which were the same size for letter pairs that have
      similar visual features across case (e.g., c/C, x/X) and dissimilar features
      (e.g., a/A, b/B). Also, the pattern of priming was the same whether the prime was
      in the same or different case as the reference. We take these findings as
      evidence that abstract letter identities support priming in this task. We suggest
      that the same-different match task is a useful tool for studying representations
      used to support masked priming in letter recognition and with other stimuli with
      limited set size.

PMID- 18609370
TI  - Revisiting the metacontrast dissociation: comparing sensitivity across different
      measures and tasks.
AB  - In the metacontrast dissociation procedure, presenting a masked shape prime prior
      to a visible shape target leads to reaction-time effects of the prime in an
      indirect measure, although participants cannot consciously detect prime shapes in
      a direct measure (Klotz & Neumann, 1999). This has been taken as evidence for the
      processing of unconscious input. The results of the present metacontrast
      dissociation study indicate that although participants are unable to consciously
      report the shape of the prime, they can consciously perceive motion between
      masked primes and visible targets in a hybrid direct/indirect measure
      (Experiments 1 and 3). This indicates that former tests did not provide an
      exhaustive measure for residual conscious perception of the prime in the
      metacontrast dissociation procedure. Further tests, however, reveal that residual
      motion perception cannot account for performance in the indirect measure
      (Experiments 2 and 3). Although the results thus leave the conception of
      processing of unconscious input intact, they may prompt a revision of its
      criteria.

PMID- 18609372
TI  - Forgotten but not gone: context effects on recognition do not require explicit
      memory for context.
AB  - Context effects on recognition memory provide an important indirect assay of
      associative learning and source memory. Neuropsychological studies have indicated
      that such context effects may obtain even if the contexts themselves are not
      remembered--for example, in individuals impaired on direct tests of memory for
      contextual information. In contrast, a recent study indicated that the effects of
      temporal context reinstatement on visual recognition obtain only when the
      contextual information itself was explicitly recollected. Here we report that the
      effects of reinstatement of spatial-simultaneous context on visual object
      recognition memory obtain irrespective of whether those context stimuli are
      explicitly recognized. We suggest that spatial-simultaneous context effects might
      be based on ensemble unitization of target and context stimuli at encoding,
      whereas temporal context effects may require recollective processes.

PMID- 18609373
TI  - Sequential or parallel decomposed processing of two-digit numbers? Evidence from
      eye-tracking.
AB  - While reaction time data have shown that decomposed processing of two-digit
      numbers occurs, there is little evidence about how decomposed processing
      functions. Poltrock and Schwartz (1984) argued that multi-digit numbers are
      compared in a sequential digit-by-digit fashion starting at the leftmost digit
      pair. In contrast, Nuerk and Willmes (2005) favoured parallel processing of the
      digits constituting a number. These models (i.e., sequential decomposition,
      parallel decomposition) make different predictions regarding the fixation pattern
      in a two-digit number magnitude comparison task and can therefore be
      differentiated by eye fixation data. We tested these models by evaluating
      participants' eye fixation behaviour while selecting the larger of two numbers.
      The stimulus set consisted of within-decade comparisons (e.g., 53_57) and between
      decade comparisons (e.g., 42_57). The between-decade comparisons were further
      divided into compatible and incompatible trials (cf. Nuerk, Weger, & Willmes,
      2001) and trials with different decade and unit distances. The observed fixation
      pattern implies that the comparison of two-digit numbers is not executed by
      sequentially comparing decade and unit digits as proposed by Poltrock and
      Schwartz (1984) but rather in a decomposed but parallel fashion. Moreover, the
      present fixation data provide first evidence that digit processing in multi-digit
      numbers is not a pure bottom-up effect, but is also influenced by top-down
      factors. Finally, implications for multi-digit number processing beyond the range
      of two-digit numbers are discussed.

PMID- 18609376
TI  - Segmenting the body into parts: evidence from biases in tactile perception.
AB  - How do we individuate body parts? Here, we investigated the effect of body
      segmentation between hand and arm in tactile and visual perception. In a first
      experiment, we showed that two tactile stimuli felt farther away when they were
      applied across the wrist than when they were applied within a single body part
      (palm or forearm), indicating a "category boundary effect". In the following
      experiments, we excluded two hypotheses, which attributed tactile segmentation to
      other, nontactile factors. In Experiment 2, we showed that the boundary effect
      does not arise from motor cues. The effect was reduced during a motor task
      involving flexion and extension movements of the wrist joint. Action brings body
      parts together into functional units, instead of pulling them apart. In
      Experiments 3 and 4, we showed that the effect does not arise from perceptual
      cues of visual discontinuities. We did not find any segmentation effect for the
      visual percept of the body in Experiment 3, nor for a neutral shape in Experiment
      4. We suggest that the mental representation of the body is structured in
      categorical body parts delineated by joints, and that this categorical
      representation modulates tactile spatial perception.

PMID- 18609377
TI  - Numerical representation: abstract or nonabstract?
AB  - Until now it has been a commonly held view that numbers are represented
      abstractly in the human brain. However, a recent imaging study challenged the
      existence of an abstract representation at least of digits and number words, at
      the brain level, and argued that previous studies and paradigms were not
      sensitive enough to detect deviations from abstract representation at the
      behavioural level. The current study addressed this issue with an analysis of
      distance and sequential effects in magnitude classification. Previous studies
      that used this paradigm did not find deviation from abstract representation for
      digits and number words (e.g., Dehaene, 1996; Schwarz & Ischebeck, 2000).
      However, in the current study a short stimulus-response interval was used, which
      reduced subjective expectancy and increased automatic processing. The current
      results showed deviation from abstract representation in both reaction time and
      accuracy and therefore support the idea that nonabstract representations of
      numbers do exist.

PMID- 18609378
TI  - Phonotactic regularities in the segmentation of spoken Italian.
AB  - Five word-spotting experiments explored the role of consonantal and vocalic
      phonotactic cues in the segmentation of spoken Italian. The first set of
      experiments tested listeners' sensitivity to phonotactic constraints cueing
      syllable boundaries. Participants were slower in spotting words in nonsense
      strings when target onsets were misaligned (e.g., lago in ri.blago) than when
      they were aligned (e.g., lago in rin.lago) with phonotactically determined
      syllabic boundaries. This effect held also for sequences that occur only word
      medially (e.g., /tl/ in ri.tlago), and competition effects could not account for
      the disadvantage in the misaligned condition. Similarly, target detections were
      slower when their offsets were misaligned (e.g., citta in cittau.ba) than when
      they were aligned (e.g., citta in citta.oba) with a phonotactic syllabic
      boundary. The second set of experiments tested listeners' sensitivity to
      phonotactic cues, which specifically signal lexical (and not just syllable)
      boundaries. Results corroborate the role of syllabic information in speech
      segmentation and suggest that Italian listeners make little use of additional
      phonotactic information that specifically cues word boundaries.

PMID- 18609379
TI  - Why do people show minimal knowledge updating with task experience: inferential
      deficit or experimental artifact?
AB  - Students generally do not have highly accurate knowledge about strategy
      effectiveness for learning, such as that imagery is superior to rote repetition.
      During multiple study-test trials using both strategies, participants'
      predictions about performance on List 2 do not markedly differ for the two
      strategies, even though List 1 recall is substantially greater for imagery. Two
      experiments evaluated whether such deficits in knowledge updating about the
      strategy effects were due to an experimental artifact or to inaccurate inferences
      about the effects the strategies had on recall. Participants studied paired
      associates on two study-test trials--they were instructed to study half using
      imagery and half using rote repetition. Metacognitive judgements tapped the
      quality of inferential processes about the strategy effects during the List 1
      test and tapped gains in knowledge about the strategies across lists. One
      artifactual explanation--noncompliance with strategy instructions--was ruled out,
      whereas manipulations aimed at supporting the data available to inferential
      processes improved but did not fully repair knowledge updating.

PMID- 18609380
TI  - Who is dominating the Dutch neighbourhood? On the role of subsyllabic units in
      Dutch nonword reading.
AB  - To assess the role of the subsyllabic units onset-nucleus (ON; spark) and rime
      (spark) in Dutch visual word recognition, we compared lexical decisions to four
      groups of nonwords in which the existence of ONs and rimes was orthogonally
      manipulated. Nonwords with existent ONs and/or rimes were rejected more slowly
      and less accurately. ON and rime neighbours thus influence Dutch nonword reading
      to the same extent. Simulations with the interactive activation model (McClelland
      & Rumelhart, 1981) revealed that this model with left-to-right coded
      representations could not replicate the effects found in the lexical decision
      data whereas an adapted version with representations of onset, nucleus, and coda
      could. Effects of the larger units ON and rime emerged from activation patterns
      created by the smaller units onset, nucleus, and coda.

PMID- 18609381
TI  - The eyes or the mouth? Feature salience and unfamiliar face processing in
      Williams syndrome and autism.
AB  - Using traditional face perception paradigms the current study explores unfamiliar
      face processing in two neurodevelopmental disorders. Previous research indicates
      that autism and Williams syndrome (WS) are both associated with atypical face
      processing strategies. The current research involves these groups in an
      exploration of feature salience for processing the eye and mouth regions of
      unfamiliar faces. The tasks specifically probe unfamiliar face matching by using
      (a) upper or lower face features, (b) the Thatcher illusion, and (c) featural and
      configural face modifications to the eye and mouth regions. Across tasks,
      individuals with WS mirror the typical pattern of performance, with greater
      accuracy for matching faces using the upper than using the lower features,
      susceptibility to the Thatcher illusion, and greater detection of eye than mouth
      modifications. Participants with autism show a generalized performance decrement
      alongside atypicalities, deficits for utilizing the eye region, and configural
      face cues to match unfamiliar faces. The results are discussed in terms of
      feature salience, structural encoding, and the phenotypes typically associated
      with these neurodevelopmental disorders.

PMID- 18609382
TI  - Evidence for an expectancy-based theory of avoidance behaviour.
AB  - In most studies on avoidance learning, participants receive an aversive
      unconditioned stimulus after a warning signal is presented, unless the
      participant performs a particular response. Lovibond (2006) recently proposed a
      cognitive theory of avoidance learning, according to which avoidance behaviour is
      a function of both Pavlovian and instrumental conditioning. In line with this
      theory, we found that avoidance behaviour was based on an integration of acquired
      knowledge about, on the one hand, the relation between stimuli and, on the other
      hand, the relation between behaviour and stimuli.

PMID- 18609383
TI  - Carrying the height of the world on your ankles: encumbering observers reduces
      estimates of how high an actor can jump.
AB  - The authors investigated how changes in action capabilities affect estimation of
      affordances for another actor. Observers estimated maximum jumping-reach height
      for themselves and another actor. Half of the observers wore ankle weights that
      reduced their jumping ability. The ankle weights reduced estimates of maximum
      jumping-reach height that observers made for themselves and for the other actor,
      but only after observers had the opportunity to walk while wearing the weights.
      Changes in estimates closely matched changes in actual jumping-reach ability.
      Results confirm and extend recent investigations that indicate that perception of
      the spatial layout of surfaces in the environment is scaled to an observer's
      capacity to act, and they link that approach to another embodied cognition
      perspective that posits a link between one's own action capabilities and
      perception of the actions of other agents.

PMID- 18609384
TI  - Multiple regression analyses in artificial-grammar learning: the importance of
      control groups.
AB  - In artificial-grammar learning, it is crucial to ensure that above-chance
      performance in the test stage is due to learning in the training stage but not
      due to judgemental biases. Here we argue that multiple regression analysis can be
      successfully combined with the use of control groups to assess whether
      participants were able to transfer knowledge acquired during training when making
      judgements about test stimuli. We compared the regression weights of judgements
      in a transfer condition (training and test strings were constructed by the same
      grammar but with different letters) with those in a control condition. Predictors
      were identical in both conditions-judgements of control participants were treated
      as if they were based on knowledge gained in a standard training stage. The
      results of this experiment as well as reanalyses of a former study support the
      usefulness of our approach.

PMID- 18609385
TI  - Evidence for modality-independent order coding in working memory.
AB  - The aim of the present study was to investigate the representation of serial
      order in working memory, more specifically whether serial order is coded by means
      of a modality-dependent or a modality-independent order code. This was
      investigated by means of a series of four experiments based on a dual-task
      methodology in which one short-term memory task was embedded between the
      presentation and recall of another short-term memory task. Two aspects were
      varied in these memory tasks--namely, the modality of the stimulus materials
      (verbal or visuo-spatial) and the presence of an order component in the task (an
      order or an item memory task). The results of this study showed impaired primary
      task recognition performance when both the primary and the embedded task included
      an order component, irrespective of the modality of the stimulus materials. If
      one or both of the tasks did not contain an order component, less interference
      was found. The results of this study support the existence of a modality
      independent order code.

PMID- 18609387
TI  - Partial reinforcement and context switch effects in human predictive learning.
AB  - Human participants were trained in a trial-by-trial contingency judgements task
      in which they had to predict the probability of an outcome (diarrhoea) following
      different cues (food names) in different contexts (restaurants). Cue P was paired
      with the outcome on half of the trials (partial reinforcement), while cue C was
      paired with the outcome on all the trials (continuous reinforcement), both cues
      in Context A. Test was conducted in both Context A and a different but equally
      familiar context (B). Context change decreased judgements to C, but not to P
      (Experiment 1). This effect was found only in the cue trained in the context
      where a different cue was partially reinforced (Experiment 2). Context switch
      effects disappeared when different cues received partial reinforcement in both
      contexts of training (Experiment 3). The implications of these results for an
      explanation of context switch effects in terms of ambiguity in the meaning of the
      cues prompting attention to the context (e.g., Bouton, 1997) are discussed.

PMID- 18609388
TI  - Configural learning without reinforcement: integrated memories for correlates of
      what, where, and when.
AB  - In 2 experiments we examined the ability of rats to form configural memories of
      what auditory stimulus (X or Y) was presented where (Context A or B) and when
      (morning or afternoon). In both experiments, rats received morning presentations
      of X in Context A and Y in Context B and afternoon presentations of X in B and Y
      in A. Subsequently, at midday the rats were exposed to trials where X was paired
      with footshock whereas Y was not. We then assessed the degree of contextual fear
      in A and B in the morning and the afternoon. In the morning, rats showed more
      fear in A than in B, and in the afternoon they showed more fear in B than in A.
      These results indicate that rats can form configural memories that represent what
      (X or Y) was presented, where (A or B), and when (morning or afternoon).

PMID- 18609389
TI  - Response demands and the recruitment of heuristic strategies in syllogistic
      reasoning.
AB  - Two experiments investigated whether dealing with a homogeneous subset of
      syllogisms with time-constrained responses encouraged participants to develop and
      use heuristics for abstract (Experiment 1) and thematic (Experiment 2)
      syllogisms. An atmosphere-based heuristic accounted for most responses with both
      abstract and thematic syllogisms. With thematic syllogisms, a weaker effect of a
      belief heuristic was also observed, mainly where the correct response was
      inconsistent with the atmosphere of the premises. Analytic processes appear to
      have played little role in the time-constrained condition, whereas their
      involvement increased in a self-paced, unconstrained condition. From a dual
      process perspective, the results further specify how task demands affect the
      recruitment of heuristic and analytic systems of reasoning. Because the
      syllogisms and experimental procedure were the same as those used in a previous
      neuroimaging study by Goel, Buchel, Frith, and Dolan (2000), the result also
      deepen our understanding of the cognitive processes investigated by that study.

PMID- 18609390
TI  - Hebb repetition effects in visual memory: the roles of verbal rehearsal and
      distinctiveness.
AB  - A version of the Hebb repetition task was used with faces to explore the
      generality of the effect in a nonverbal domain. In the baseline condition, a
      series of upright faces was presented, and participants were asked to reconstruct
      the original order. Performance in this condition was compared to another in
      which the same stimuli were accompanied by concurrent verbal rehearsal to examine
      whether Hebb learning is dependent on verbal processing. Baseline performance was
      also compared to a condition in which the same faces were presented inverted.
      This comparison was used to determine the importance in Hebb learning of being
      able to visually distinguish between the list items. The results produced classic
      serial position curves that were equivalent over conditions with Hebb repetition
      effects being in evidence only for upright faces and verbal suppression as having
      no effect. These findings are interpreted as posing a challenge to current models
      derived from verbal-domain data.

PMID- 18609391
TI  - EPS Prize Lecture. Learning to read words.
AB  - The ease with which we process the written word belies its complexities and makes
      it easy to forget that it is a highly skilled behaviour and one that takes time
      to master. In this paper, I argue that our ability to read words has its roots in
      our capacity for language. Good progress has been made towards understanding how
      children discover the systematic relationship between speech sounds and the
      letters used to represents those sounds, very early in reading development.
      However, we understand much less about how beginning readers become skilled
      readers. To understand this, I argue that it is important to view the visual word
      recognition system within the context of a broader language system, one that
      incorporates a rich network of semantic and episodic knowledge.

PMID- 18609392
TI  - Location- and object-based inhibition of return are affected by different kinds
      of working memory.
AB  - Castel, Pratt, and Craik (2003) have shown that inhibition of return (IOR, the
      delayed response to a recently cued item) is disrupted by a secondary task that
      involves spatial working memory (WM), and they suggest that IOR is mediated by
      spatial WM. However, they did not specify what kind of IOR was involved. We used
      a dual-task paradigm to examine whether the two kinds of IOR (location- and
      object-based IOR) are affected by two kinds of secondary task that involve
      spatial and nonspatial WM, respectively. The results show that location-based IOR
      was disrupted by a spatial secondary task while the object-based IOR was
      disrupted by a nonspatial secondary task. The present study further elaborates
      the conclusion of Castel et al. (2003) by differentiating the effect of the two
      kinds of WM (spatial vs. nonspatial) on the two kinds of IOR (location based vs.
      object based).

PMID- 18609393
TI  - Reduced orthographic learning in dyslexic adult readers: evidence from patterns
      of letter search.
AB  - Visual letter search performance was investigated in a group of dyslexic adult
      readers using a task that required detection of a cued letter target embedded
      within a random five-letter string. Compared to a group of skilled readers,
      dyslexic readers were significantly slower at correctly identifying targets
      located in the first and second string position, illustrating significantly
      reduced leftward facilitation than is typically observed. Furthermore, compared
      to skilled readers, dyslexic readers showed reduced sensitivity to positional
      letter frequency. They failed to exhibit significantly faster response times to
      correctly detect target letters appearing in the most, compared to least,
      frequent letter position within five-letter words, and response times correlated
      with positional letter frequency only for the initial, and not the final, letter
      position. These results are compatible with the SERIOL (sequential encoding
      regulated by inputs to oscillations within letter units) model of orthographic
      processing proposed by Whitney and Cornelissen (2005). Furthermore, they suggest
      that dyslexic readers are less efficient than skilled readers at learning to
      extract statistical regularities from orthographic input.

PMID- 18609394
TI  - Mediated conditioning versus retrospective revaluation in humans: the influence
      of physical and functional similarity of cues.
AB  - Two experiments assessed whether similarity between the two elements of a
      compound would influence the degree of mediated extinction versus recovery from
      overshadowing in human causal judgements. In both Experiments 1 and 2, we
      assessed the influence of extinguishing one element of a two-element compound on
      judgements about the other element. In Experiment 1 we manipulated the physical
      similarity of the two elements of the compound; in Experiment 2, we used
      equivalence and distinctiveness pretraining in order to vary their functional
      similarity. We found that these procedures influenced mediated extinction and
      recovery from overshadowing as a function of both physical and acquired
      similarity and distinctiveness, respectively. The implications of these results
      for previously reported differences between humans and nonprimate animals are
      discussed.

PMID- 18609395
TI  - Extinction in human learning and memory.
AB  - In two experiments, participants were given extinction training in a human causal
      learning task. In both experiments, three critical experimental cues were paired
      with different outcomes in a first phase of training and were then extinguished
      in a second phase. Three control cues were given the same treatment in the first
      phase of training, but were not then presented in the second phase. Participants'
      ability to correctly identify the outcome with which each cue had been paired in
      the first phase was lower for extinguished than for control cues. Causal
      attributions to the extinguished cues were also lower than those to the control
      cues, a difference that correlated with outcome memory. These data are consistent
      with the idea that extinction in causal judgement is due, at least in part, to a
      failure to remember the cue-outcome relationship encoded in the first phase of
      training.

PMID- 18609396
TI  - Spatial memory and explicit knowledge: an effect of instruction on
      representational momentum.
AB  - Freyd (1987; Finke & Freyd, 1985) suggested that representational momentum (i.e.,
      forward displacement in memory for the location of a moving target) is impervious
      to error feedback (i.e., is modular or cognitively impenetrable), but studies
      supporting this claim might not have allowed sufficient opportunity for learning
      to occur. In the experiment reported here, participants were (a) naive regarding
      representational momentum, (b) informed about representational momentum but not
      instructed to counteract it, or (c) informed about representational momentum and
      instructed to counteract it. All participants exhibited significant displacement.
      However, participants informed about representational momentum exhibited less
      forward displacement than did naive participants due to a greater tendency to
      respond same to probes behind the true--same position. Possible mechanisms of
      compensation and the notion that displacement reflects both modular (cognitively
      impenetrable) and nonmodular (cognitively penetrable) components are addressed.

PMID- 18609397
TI  - What determines auditory similarity? The effect of stimulus group and
      methodology.
AB  - Two experiments on the internal representation of auditory stimuli compared the
      pairwise and grouping methodologies as means of deriving similarity judgements. A
      total of 45 undergraduate students participated in each experiment, judging the
      similarity of short auditory stimuli, using one of the methodologies. The
      experiments support and extend Bonebright's (1996) findings, using a further 60
      stimuli. Results from both methodologies highlight the importance of category
      information and acoustic features, such as root mean square (RMS) power and
      pitch, in similarity judgements. Results showed that the grouping task is a
      viable alternative to the pairwise task with N > 20 sounds whilst highlighting
      subtle differences, such as cluster tightness, between the different task
      results. The grouping task is more likely to yield category information as
      underlying similarity judgements.

PMID- 18609398
TI  - Analysing the relationship between target-to-target and distractor-to-target
      repetitions: evidence for a common mechanism.
AB  - In the present study an assumption of retrieval theories of negative priming was
      tested. In particular, retrieval theories assume that the same underlying process
      causes benefits in target-to-target repetition trials and cost effects in
      distractor-to-target repetition trials in selection tasks in which targets are
      accompanied by distractor stimuli. More specifically, retrieval theories predict
      a negative correlation: The higher the benefit in target-to-target repetition
      trials is, the higher the cost effect in distractor-to-target repetition trials
      should be. In fact, in a study with considerable power (N = 110) and a design
      that allowed a confound-free detection of correlations, I observed a significant
      negative correlation between benefit and cost effects. This result is interpreted
      as evidence for a common retrieval mechanism.

PMID- 18609399
TI  - Detrended windowed (lag one) autocorrelation: a new method for distinguishing
      between event-based and emergent timing.
AB  - The aim of this study was to test different methods for distinguishing between
      two known timing processes involved in human rhythmic behaviours. We examined the
      implementation of two approaches used in the literature: the high-frequency slope
      of the power spectrum and the lag one value of the autocorrelation function,
      ACF(1). We developed another method based on the Wing and Kristofferson (1973a)
      model and the predicted negative ACF(1) for event-based series: the detrended
      windowed (lag one) autocorrelation (DWA). We compared the reliability and
      performance of these three methods on simulation and experimental series. DWA
      gave the best results, and guidelines are given for its appropriate use for
      identifying underlying timing processes.

PMID- 18609400
TI  - Minimizing the influence of recoding in the Implicit Association Test: the
      Recoding-Free Implicit Association Test (IAT-RF).
AB  - Recoding processes can influence the Implicit Association Test (IAT; Greenwald,
      McGhee, & Schwartz, 1998) in a way that impedes an unequivocal interpretation of
      the resulting compatibility effects. We present a modified version of the IAT
      that aims to eliminate recoding, the IAT-RF (short for "IAT-recoding free"). In
      the IAT-RF, compatible and incompatible assignments of categories to responses
      switch randomly between trials within a single experimental block. Abandoning an
      extended sequence of consistent category-response mappings undermines recoding
      processes in the IAT-RF. Two experiments reveal that the IAT-RF is capable of
      assessing compatibility effects between the nominally defined categories of the
      task and effectively prevents recoding. By enforcing a processing of the stimuli
      in terms of their task-relevant category membership, the IAT-RF eliminates the
      confounding of compatibility effects with task switch costs and becomes immune
      against biased selections of stimuli.

PMID- 18609401
TI  - The varying effects of age of acquisition.
AB  - There are a number of theories that suggest that age of acquisition (AoA) effects
      are not uniform across different tasks. Catling and Johnston (2006a) found
      greater AoA effects within an object-naming task than in a semantic
      classification task. They explained these findings by suggesting that AoA effects
      might accumulate according to how many levels of representation a task
      necessitates access to. Brysbaert and Ghyselinck (2006) explain the difference in
      AoA effects by proposing two distinct types of AoA (frequency dependent and
      frequency independent), the first accounted for by a connectionist-type mechanism
      and the latter situated at the interface between semantics and word production.
      Moreover, Moore, Smith-Spark, and Valentine (2004) and Holmes and Ellis (2006)
      have suggested that there are two loci of AoA effects: at the phonological level
      and somewhere within the perceptual level of representation. Again, this could
      account for the varying degrees of AoA effects. This study sets about testing
      these ideas by assessing the effect size of AoA across a series of different
      tasks that necessitate access to various levels of representation. Experiments 1
      4 demonstrate significant effects of AoA in a novel picture-picture verification
      task, an object classification task, a picture verification task, and an object
      naming task. Experiment 5 showed no effects of initial phoneme on the naming of
      the critical objects used within Experiments 1-4. The implication of the varying
      AoA effect sizes found within Experiments 1-4 in relation to explanations of AoA
      are discussed.

PMID- 18609402
TI  - Voluntary and involuntary attention have different consequences: the effect of
      perceptual difficulty.
AB  - We propose that voluntary and involuntary attention affect different mechanisms
      and have different consequences for performance measured in reaction time.
      Voluntary attention enhances the perceptual representation whereas involuntary
      attention affects the tendency to respond to stimuli in one location or another.
      In a spatial-cueing paradigm, we manipulated perceptual difficulty and compared
      voluntary and involuntary attention. For the voluntary-attention condition, the
      spatial cue was predictive of the target location, whereas in the involuntary
      attention condition it was not. Increasing perceptual difficulty increased the
      attention effect with voluntary attention, but decreased it with involuntary
      attention. Thus voluntary and involuntary attention have different consequences
      when perceptual difficulty is manipulated and hence are probably caused by
      different mechanisms.

PMID- 18609403
TI  - The effects of precedence on Navon-induced processing bias in face recognition.
AB  - Macrae and Lewis (2002) showed that repeated reporting of the global dimension of
      Navon stimuli improved performance in a subsequent face identification task,
      whilst reporting the features of the Navon stimuli impaired performance. Using a
      face composite task, which is assumed to require featural processing, Weston and
      Perfect (2005) showed the complementary pattern: Featural responding to Navon
      letters speeded performance. However, both studies used Navon stimuli with global
      precedence, in which the overall configuration is easier to report than the
      features. Here we replicate the two studies above, whilst manipulating the
      precedence (global or featural) of the letter stimuli in the orientation task.
      Both studies replicated the previously reported findings with global precedence
      stimuli, but showed the reverse pattern with local precedence stimuli. These data
      raise important questions as to what is transferred between the Navon orientation
      task and the face-processing tasks that follow.

PMID- 18609404
TI  - Information structure expectations in sentence comprehension.
AB  - In English, new information typically appears late in the sentence, as does
      primary accent. Because of this tendency, perceivers might expect the final
      constituent or constituents of a sentence to contain informational focus. This
      expectation should in turn affect how they comprehend focus-sensitive
      constructions such as ellipsis sentences. Results from four experiments on
      sluicing sentences (e.g., The mobster implicated the thug, but we can't find out
      who else) suggest that perceivers do prefer to place focus late in the sentence,
      though that preference can be mitigated by prosodic information (pitch accents,
      Experiment 2) or syntactic information (clefted sentences, Experiment 3)
      indicating that focus is located elsewhere. Furthermore, it is not necessarily
      the direct object, but the informationally focused constituent that is the
      preferred antecedent (Experiment 4). Expectations regarding the information
      structure of a sentence, which are only partly cancellable by means of overt
      focus markers, may explain persistent biases in ellipsis resolution.

PMID- 18609405
TI  - The representation of negative numbers: exploring the effects of mode of
      processing and notation.
AB  - The representation of negative numbers was explored during intentional processing
      (i.e., when participants performed a numerical comparison task) and during
      automatic processing (i.e., when participants performed a physical comparison
      task). Performance in both cases suggested that negative numbers were not
      represented as a whole but rather their polarity and numerical magnitudes were
      represented separately. To explore whether this was due to the fact that polarity
      and magnitude are marked by two spatially separated symbols, participants were
      trained to mark polarity by colour. In this case there was still evidence for a
      separate representation of polarity and magnitude. However, when a different set
      of stimuli was used to refer to positive and negative numbers, and polarity was
      not marked separately, participants were able to represent polarity and magnitude
      together when numerical processing was performed intentionally but not when it
      was conducted automatically. These results suggest that notation is only partly
      responsible for the components representation of negative numbers and that the
      concept of negative numbers can be grasped only through that of positive numbers.

PMID- 18609406
TI  - Independent effects of colour on object identification and memory.
AB  - We examined the effects of colour on object identification and memory using a
      study-test priming procedure with a coloured-object decision task at test (i.e.,
      deciding whether an object is correctly coloured). Objects were selected to have
      a single associated colour and were either correctly or incorrectly coloured. In
      addition, object shape and colour were either spatially integrated (i.e., colour
      fell on the object surface) or spatially separated (i.e., colour formed the
      background to the object). Transforming the colour of an object from study to
      test (e.g., from a yellow banana to a purple banana) reduced priming of response
      times, as compared to when the object was untransformed. This utilization of
      colour information in object memory was not contingent upon colour falling on the
      object surface or whether the resulting configuration was of a correctly or
      incorrectly coloured object. In addition, we observed independent effects of
      colour on response times, whereby coloured-object decisions were more efficient
      for correctly than for incorrectly coloured objects but only when colour fell on
      the object surface. These findings provide evidence for two distinct mechanisms
      of shape-colour binding in object processing.

PMID- 18609407
TI  - Dynamic action in virtual environments: constraints on the accessibility of
      action knowledge in children and adults.
AB  - In a series of three experiments, we probed the accessibility of action knowledge
      in different versions of a virtual environment (VE) with 7-year-old children and
      adults. Using a PHANToM haptic interface, participants performed a virtual
      throwing task in which they tried to propel a ball from a table to hit a target
      on the ground. In Experiments 1 and 2, the virtual scene was presented on a
      computer monitor, and, in Experiment 3, it was projected by using a video
      projector so that the vertical and horizontal dimensions and the spatial location
      of the VE corresponded to the real-world dimensions. Results indicate that action
      knowledge is accessible even in a nonimmersive VE, but also suggest that the need
      to recalibrate perceptual-motor mappings constrains the accessibility of this
      kind of intuitive knowledge.

PMID- 18609409
TI  - Age of acquisition's effect on memory for semantically associated word pairs.
AB  - This experiment investigated the effects of age of acquisition (AoA) in memory
      for associated word pairs in a cued recall task. Participants studied a list of
      frequency-controlled early- and late-acquired words in semantically related pairs
      and then were asked to recall the second word of the pair when cued with the
      first. Reaction time effects were found, showing that a late-acquired cue for an
      early-acquired target word was responded to significantly faster than other
      combinations. Additionally, late-acquired target words resulted in significantly
      more accurate responses. As significant differences were found even when
      frequency was controlled, the effects must therefore stem from the manipulations
      ofAoA. Given this evidence, the implications for AoA's effects on the
      organization of semantic memory are explored.

PMID- 18609408
TI  - Inhibition of irrelevant category-response mappings.
AB  - When switching tasks, performance tends to be worse for n - 2 repetitions than
      with n - 2 switches. This n - 2 repetition cost has been hypothesized to reflect
      task-set inhibition: specifically, inhibition of irrelevant category-response
      mappings involved in response selection. This hypothesis leads to divergent
      predictions for situations in which all tasks involve the same stimulus
      categories: An n - 2 repetition cost is predicted when response sets differ
      across tasks, but not when the response set stays the same. The authors tested
      these predictions by having subjects perform relative judgements with different
      reference points. In Experiment 1, the stimulus categories were the same across
      reference points, but the response set either differed or stayed the same (the
      multiple- and single-mapping conditions, respectively). An n - 2 repetition cost
      was found in the multiple-mapping condition but not in the single-mapping
      condition. Experiment 2 provided evidence against the possibility that these
      divergent effects reflected differences in memory load. These findings confirm
      predictions that link n - 2 repetition costs to inhibition of irrelevant category
      response mappings.

PMID- 18609410
TI  - Adaptation to sensory-motor temporal misalignment: instrumental or perceptual
      learning?
AB  - Sensory-motor delays vary over the course of development and under different
      environmental conditions. Previous research has shown that humans can compensate
      for the resulting temporal misalignment while performing sensory-motor tasks
      (e.g., Cunningham, Billock, & Tsou, 2001a), but remains silent on the question of
      whether perceptual learning-similar to that involved in adaptation to spatial
      misalignment (e.g., Redding & Wallace, 1993) and in adaptation to purely
      intersensory misalignment (e.g., Fujisaki, Shimojo, Kashino, & Nishida, 2004)-is
      also involved in this adaptive response. Following an attempted replication of
      Cunningham et al.'s (2001a) study in a preliminary experiment, we present in this
      paper two experiments that demonstrate that after-effects of adaptation to
      temporal misalignment do not spontaneously decay. The literature on adaptation to
      spatial misalignment suggests that, while instrumental learning spontaneously
      decays in the absence of reinforcement, perceptual learning persists. Therefore
      our results are consistent with adaptation being effected through perceptual
      learning.

PMID- 18609411
TI  - Task-defined associations are mode specific for selection of relevant dimension
      but mode independent for selection of location mapping.
AB  - When compatible and incompatible mappings of a location-relevant task are mixed,
      or a location-relevant task is mixed with a task for which stimulus location is
      irrelevant, the benefit of the compatible mapping is eliminated for physical
      locations and enhanced for location words. Two experiments examined the influence
      of presenting the location information for the mixed conditions in different
      stimulus modes (physical location or word). Experiment 1 showed that the effects
      of mixing location-relevant and location-irrelevant tasks on the spatial
      compatibility and Simon effects are reduced when the location information is
      presented in different modes for the two tasks. Experiment 2 showed, in contrast,
      that the mode distinction had little influence on the effects of mixed compatible
      and incompatible mappings for location-relevant tasks: The compatibility effect
      was eliminated for physical locations and enhanced for words, as when there is no
      mode distinction. Thus, when location is relevant for one task and colour for the
      other, the task-defined associations of locations to responses are mode specific,
      but when location is relevant for both tasks, the associations are mode
      independent.

PMID- 18609412
TI  - Applying an exemplar model to the artificial-grammar task: inferring
      grammaticality from similarity.
AB  - We present three artificial-grammar experiments. The first used position
      constraints, and the second used sequential constraints. The third varied both
      the amount of training and the degree of sequential constraint. Increasing both
      the amount of training and the redundancy of the grammar benefited participants'
      ability to infer grammatical status; nevertheless, they were unable to describe
      the grammar. We applied a multitrace model of memory to the task. The model used
      a global measure of similarity to assess the grammatical status of the probe and
      captured performance both in our experiments and in three classic studies from
      the literature. The model shows that retrieval is sensitive to structure in
      memory, even when individual exemplars are encoded sparsely. The work ties an
      understanding of performance in the artificial-grammar task to the principles
      used to understand performance in episodic-memory tasks.

PMID- 18609413
TI  - Volitional disorders: a proposal for DSM-V.
AB  - In the DSM-IV-TR, specific impulse control disorders not elsewhere classified
      (ICD) have been designated following four principles: (1) through the addition of
      an adjective that emphasizes the aberrant character of an otherwise normal
      behaviour (e.g., pathological gambling); (2) by means of metaphors (such as in
      intermittent explosive disorder); (3) according to the presumably quintessential
      nature of their main signs and symptoms, such as impulsive (e.g., impulse control
      disorders not elsewhere classified), compulsive (e.g., compulsive shopping), or
      addictive (e.g., internet addiction); or (4) using Greek suffix mania (e.g.,
      kleptomania, pyromania, and trichotillomania). Given this flagrant inconsistency,
      we argue that time has come to adopt a less arbitrary way of describing these
      disorders, at least until it becomes clearer whether they are really impulsive,
      compulsive or addictive or if the preoccupation with this distinction is valid.
      In keeping with DSM's emphasis on descriptive phenomenology rather than on
      unsupported theory, a less biased terminology is in order. Therefore, we would
      like to suggest: (1) the substitution of the term ICD by the more neutral
      expression 'volitional disorders not elsewhere classified'; (2) the use of the
      classical Greek suffix mania, already present in some DSM-IV-TR ICDs, as the main
      naming principle to be adopted in the DSM-V; and (3) the creation of compulsive,
      impulsive, and mixed subtypes of the 'volitional disorders not elsewhere
      classified', since they are beginning to be validated by treatment trials.

PMID- 18609414
TI  - Movement sequencing abilities and basal ganglia morphology in first-episode
      schizophrenia.
AB  - INTRODUCTION: Studies of brain morphology suggest a link between movement
      sequencing ability and basal ganglia dysfunction. Unfortunately, relevant studies
      have provided inconsistent data, which may be the result of differences in the
      methods of brain morphology assessment, statistical analysis or heterogeneity of
      the populations studied. AIM: To test the hypothesis of a link between the
      dysfunction of movement sequencing and basal ganglia morphology in a homogenous
      sample of first-episode schizophrenia patients. METHOD: Thirty-seven first
      episode schizophrenia patients underwent an assessment of movement sequencing
      abilities using the NES scale and basal ganglia morphology from MR images. The
      data were compared with a group of 19 age- and sex-matched healthy controls.
      RESULTS: The group of first-episode patients had a higher concentration of gray
      matter than healthy controls in the putamen and pallidum in both hemispheres.
      Patients with abnormal sequencing of movements had lower gray matter
      concentration than patients without such abnormalities in the left putamen, and
      no differences were found between the symptomatic group and healthy controls.
      SUMMARY AND CONCLUSION: Our study suggests the involvement of the left putamen in
      the movement sequencing abnormalities in schizophrenia. Because of the potential
      confounding effect of medication, the lack of support from external evidence and
      the low power to perform the whole-brain analysis the results should be
      considered as preliminary. Further studies, especially with antipsychotic-naive
      first-episode schizophrenia patients are needed to solve these issues.

PMID- 18609415
TI  - Stereopsis and magnocellular sensitivity in schizophrenia.
AB  - There is evidence to indicate that schizophrenic individuals, in addition to
      cognitive deficiencies, also suffer from visual deficits. These deficits, it has
      been proposed, are the result of a deficiency in the magnocellular portion of the
      early visual system. A number of approaches have been used in attempts to assess
      the sensitivity of the magnocellular system in individuals with schizophrenia. It
      has recently been proposed that magnocellular sensitivity can be tested by
      measuring stereo acuity, i.e. by measuring the accuracy with which visual depth
      can be detected based on differences in the retinal images in the two eyes. This
      suggestion was based on early claims which linked stereopsis, i.e. the visual
      perception of depth generated from differences in the two retinal images, to the
      magnocellular system. We here review more recent results which indicate that
      stereopsis and stereo acuity are more closely linked to the parvocellular system.
      It is concluded that stereo acuity is not an appropriate test for assessing
      magnocellular sensitivity. The present considerations undermine the claim that
      magnocellular deficits are linked to schizophrenia.

PMID- 18609416
TI  - Limbic encephalitis presenting with anxiety and depression: a comprehensive
      neuropsychological formulation.
AB  - Limbic encephalitis (LE) is a paraneoplastic neurological disorder in which,
      typically, the neurological symptoms occur before the cancer is diagnosed. We
      report on a 52-year-old male with LE who has depressive and anxiety symptoms.
      Cranial MRI revealed increased hippocampal signal intensities in both temporal
      lobes. Extensive range of symptoms concerning emotion, personality and social
      functioning was assessed with a comprehensive neuropsychological formulation. The
      neuropsychological test battery showed dysfunction of hippocampus, medial
      temporal lobes, limbic system and frontal diencephalic structures. The current
      literature about the neurological mechanisms underlying the neuropsychological
      findings of LE is also briefly reviewed in this report.

PMID- 18609418
TI  - Cognitive impairment of executive function as a core symptom of schizophrenia.
AB  - Cognitive dysfunction is a common finding in schizophrenia. Nevertheless the
      specific pattern of neuropsychological impairment in schizophrenia compared to
      other severe mental illnesses has not been intensively studied. Twenty-four
      patients with schizophrenia belonging to different stages of the disease (11
      first-episode patients, 13 patients with multiple episodes), 18 patients with
      bipolar disorder and 23 healthy control subjects underwent standardized
      neuropsychological assessment. Statistical analysis of covariance (ANCOVA)
      demonstrated that, compared to control subjects, patients with schizophrenia
      performed significantly worse in the trail-making test (P = 0.012), verbal
      fluency (category letter, P = 0.004), verbal learning/memory (P = 0.005), and the
      Wisconsin Card Sorting Test (WCST) (P = 0.004 for administered trials; P = 0.025
      for perseverative responses, T value) indicating significant deficits in
      attention and psychomotor performance, and in particular in verbal working memory
      and cognitive flexibility for schizophrenic patients. A significant difference
      between schizophrenic and bipolar patients was found only in the WCST.
      Schizophrenic patients made significantly more perseverative responses (P =
      0.002, ANCOVA), indicating a more pronounced and specific deficit in cognitive
      flexibility and frontally based executive function. In conclusion, these results
      may suggest a cognitive endophenotype in schizophrenia and underline the role of
      the prefrontal cortex in schizophrenic pathophysiology.

PMID- 18609419
TI  - Hippocampal remodelling after MDMA neurotoxicity: a single case study.
AB  - Acute ingestion of MDMA (ecstasy) causes a transient marked increase in serotonin
      and dopamine at central synapses. Recent studies demonstrated that MDMA induces
      damage of serotonergic nerve terminals and alters hippocampal processing.
      Pronounced cognitive deficits in MDMA users affect learning and memory abilities.
      This pattern of predominant and long-lasting memory dysfunction suggests that the
      functioning of the hippocampus might be affected by the neurotoxic effects of
      MDMA. We present the case of a 16-year-old girl who developed an acute organic
      and psychotic syndrome caused by occasional use of low to moderate dose of MDMA.
      Serial neuroimaging ((18)F-FDG-PET and brain MRI) were correlated with her
      neurocognitive performance and clinical evolution. The structural and metabolic
      changes correlated with a severe cognitive impairment. After 16 months of
      intensive neuropsychological rehabilitation she showed significant improvement in
      hippocampal-related memory cognitive functions, which correlated with
      normalization of her (18)F-FDG-PET and remarkable hippocampal remodelling. This
      case report indicates that even non-chronic MDMA use may cause subacute toxic
      encephalopathy in which the clinical evolution is paralleled by neuroimaging
      changes in specific cerebral areas. The most relevant aspect is the reversibility
      of the volumetric changes, which may be the structural correlate of an ongoing
      hippocampal remodelling.

PMID- 18609420
TI  - Lithium but not carbamazepine augments antidepressant efficacy of mirtazapine in
      unipolar depression: an open-label study.
AB  - BACKGROUND: The purpose of the present open-label study was to investigate the
      antidepressant efficacy of lithium and carbamazepine as augmentation strategies
      in unipolar depressed inpatients. METHOD: Forty-six patients suffering from
      unipolar depression (major depressive episode according to DSM-IV criteria) were
      pre-treated with mirtazapine for 2 weeks initially (week -2 to week 0).
      Thereafter, the patients received either continuation of mirtazapine monotherapy
      (n = 23), combination treatment with mirtazapine and lithium (n = 13), or
      combination therapy with mirtazapine and carbamazepine (n = 10) for further 3
      weeks (week 0 to week 3). Severity of depression was estimated weekly using the
      21-item version of the Hamilton Depression Rating Scale (21-HAMD). Response was
      defined by a reduction of at least 50% in the 21-HAMD sum score after 3 weeks of
      pharmacotherapy (week 0-3). RESULTS: Additional administration of lithium, but
      not adjunctive carbamazepine significantly augmented the antidepressant efficacy
      of mirtazapine in the unipolar depressed patients. Moreover, carbamazepine but
      not lithium significantly lowered the serum concentrations of mirtazapine.
      CONCLUSION: Whereas the clinical importance of anticonvulsants in the treatment
      of bipolar disorder is not in doubt, the therapeutic efficacy of antiepileptic
      drugs such as carbamazepine is obviously limited in the pharmacotherapy of
      unipolar depression.

PMID- 18609421
TI  - Inappropriate crying and laughing in Parkinson disease and movement disorders.
AB  - OBJECTIVE: To examine in a pilot study inappropriate crying and laughing (also
      termed pseudobulbar affect (PBA)) and underlying mood disturbances in a large
      clinic based population of Parkinson's disease and movement disorder patients.
      BACKGROUND: PBA is characterized by uncontrollable laughter without mirth, or
      alternatively crying without the feeling of sadness. It is a common condition
      affecting more than one million people with neurological diseases. While PBA has
      been studied in many neurological diseases, little is known about its prevalence
      in movement disorders, or its relationship to more chronic mood disturbances. We
      carried out this pilot study to examine this relationship. METHODS: Seven hundred
      and nineteen out of 860 consecutive patients who visited our Movement Disorders
      Center met inclusion criteria (i.e. > or = 18 years of age, formal diagnosis by a
      movement disorder specialist, completion of PBA questionnaire, and absence of
      brain surgery including deep brain stimulation). All subjects were interviewed
      for symptoms of PBA during their visit. In addition, 661 of these patients
      completed both the Visual Analog Mood Scale (VAMS) and Beck Depression Inventory
      I (BDI-I). RESULTS: Thirty-seven of the 719 reported PBA symptoms; 75.7% (28/37)
      had pathological 'crying', 13.5% (5/37) had pathological 'laughing' and 10.8%
      (4/37) had both. The prevalence of PBA in individual diagnostic categories was:
      4.7% (18/387) of idiopathic Parkinson's disease (PD), 2.7% (2/74) of primary
      dystonia, 3.1% (2/65) of essential tremor (ET), 7.8% (8/108) of patients with
      other forms of Parkinsonism, 21.7% (5/23) of psychogenic movement disorders, 0%
      (0/18) of patients with combined PD and ET, and 4.5% (2/44) of other movement
      disorders. Patients with PBA had a higher total BDI score (P=0.0278) and VAMS
      'tiredness' score (P=0.0109). In patients on antidepressant therapy the
      prevalence of PBA was 7.1% compared to 2.7% in the group not on therapy
      (P=0.0094). CONCLUSION: PBA was present in most movement disorders, but
      especially prevalent in parkinsonism. PBA patients in this cohort had more
      chronic depressive symptoms and tiredness.

PMID- 18609422
TI  - The effect of melatonergic and non-melatonergic antidepressants on sleep:
      weighing the alternatives.
AB  - In DSM-IV the occurrence of disturbed sleep is one of the principal diagnostic
      criteria for major depressive disorder (MDD). Further, there is evidence of
      reciprocity between the two conditions such that, even in the absence of current
      depressive symptoms, disturbed sleep often predicts their development. The
      present review discusses the effects of antidepressants on sleep and evaluates
      the use of the recently developed melatonin agonist-selective serotonin
      antagonists on sleep and depression. Although many antidepressants such as the
      tricyclics, monoamine oxidase inhibitors, serotonin-norepinephrine reuptake
      inhibitors, several serotonin receptor antagonists and selective serotonin
      reuptake inhibitors (SSRIs) have all been found successful in treating
      depression, their use is often associated with a disruptive effect on sleep.
      SSRIs, currently the most widely prescribed of the antidepressants, are well
      known for their instigation or exacerbation of insomnia. The recently introduced
      novel melatonin agonist and selective serotonin antagonist antidepressant,
      agomelatine, which has melatonin MT(1) and MT(2) receptor agonist and 5-HT(2c)
      antagonist properties, has been useful in treating patients with MDD. Its rapid
      onset of action and effectiveness in improving the mood of depressed patients has
      been attributed to its ability to improve sleep quality. These properties
      underline the use of melatonin analogues as a promising alternative for the
      treatment of depression.

PMID- 18609423
TI  - Unilateral rubral tremor following treatment with risperidone.
AB  - Rubral tremor is a rare movement disorder that occurs typically with midbrain
      damage. The main features of this tremor are its low frequency, irregular rhythm,
      presence at rest, and acceleration during posture and active movement.
      Antipsychotic agent-induced tremors are usually bilateral parkinsonian tremors.
      We found no previous reports of unilateral rubral tremor in the literature. A 23
      year-old man had unilateral rubral tremors as a result of a midbrain lesion plus
      risperidone exposure for treatment of manic symptoms. After we stopped the use of
      risperidone, the tremor became less apparent and then disappeared. This case
      highlights the importance of being aware of this rare complication in susceptible
      patients receiving risperidone treatment.

PMID- 18609424
TI  - Urinary incontinence associated with amisulpride.

PMID- 18609425
TI  - Infections as complications of neuroleptic malignant syndrome.
AB  - Neuroleptic malignant syndrome is an uncommon but potentially fatal side effect
      of antipsychotic drug treatment. Several serious complications have been
      associated with neuroleptic malignant syndrome, such as acute renal failure, deep
      venous thrombosis, pulmonary embolism and aspiration pneumonia. Reports on
      infections other than aspiration pneumonia appear, from the literature, to be
      uncommon. Four cases of infection (three cases of upper respiratory tract
      infection and one case of urinary tract infection) which developed during the
      course of neuroleptic malignant syndrome are reported and pathophysiological
      mechanisms underlying their presentation are suggested.

PMID- 18609426
TI  - Increased motor activity in cycloid psychosis compared to schizophrenia.
AB  - Although cycloid psychoses share psychopathological features with schizophrenia,
      their course and outcome are comparable to those seen in bipolar affective
      disorder. The diagnostic category is of interest because it has been demonstrated
      that cycloid psychoses can be diagnosed reliably and distinguished from other
      psychoses based on treatment response and neurophysiology. Despite this, only few
      studies have investigated the neurobiological differences between cycloid
      psychoses and schizophrenia, and although hyper- and hypoactivity have been
      observed in patients with cycloid psychoses, no studies have investigated motor
      activity in this group to date. Therefore, we aimed to quantify motor activity
      during the waking hours of the day as assessed by wrist actigraphy in 16 patients
      with cycloid psychosis and 16 patients with paranoid schizophrenia. All patients
      were matched for gender and age, and wrist actigraphic assessment took place
      during acute episodes. The level of activity and proportion of active vs.
      inactive periods during waking hours were significantly higher in patients with
      cycloid psychosis. The results of the present study are interpreted in light of a
      previously reported general arousal in cycloid psychoses that is expressed in
      motor activity. Our data support the concept of cycloid psychoses as a syndrome
      with distinct symptomatology and pathophysiology.

PMID- 18609427
TI  - Spectroscopic findings in attention-deficit/hyperactivity disorder: review and
      meta-analysis.
AB  - OBJECTIVES: The last decade has seen an increasing interest in the method of
      magnet resonance spectroscopy (MRS) since this is the only research tool that
      allows a non-invasive in vivo assessment of neurochemical aspects of ADHD without
      employing ionising radiation. In this paper we review published MRS results with
      respect to childhood, adolescence and adult ADHD. METHOD: We searched the Medline
      (Pub Med) database using the key words ADHD, attention-deficit/hyperactivity
      disorder, magnet resonance spectroscopy, MRS and spectroscopy. Citations of
      identified articles were also searched for relevant studies. Meta-analyses were
      performed for the measured metabolites and regions of assessment. RESULTS:
      Sixteen studies could be identified that used MRS to investigate the neurobiology
      of ADHD. Two regions could be identified as the focus of spectroscopic
      investigations--the frontal lobe including anterior cingulate cortex and parts of
      prefrontal cortex and the basal ganglia, mostly striatum, alongside the fronto
      striato-thalamo-frontal circuits. As for metabolites, in the majority of studies
      the ratios to creatine and not absolute concentrations of metabolites were
      estimated. Choline compounds, N-acetyl-aspartate and glutamate/glutamine (to
      creatine ratios) could be identified as being altered in several studies in ADHD.
      The meta-analysis showed increased choline compounds in several researched
      regions. DISCUSSION: MRS is a promising tool for the non-invasive in vivo
      assessment of the cerebral neurochemistry in ADHD. More regions of interest (ROI)
      like amygdala, hippocampus, thalamus and cerebellum should be assessed in future
      studies. Further methodological improvements of MRS are desirable in order to
      assess the absolute metabolite concentration of several ROIs at the same time.
      Such developments will open novel perspectives in spectroscopic investigations of
      ADHD.

PMID- 18609429
TI  - The neural substrates of affective face recognition in patients with Hwa-Byung
      and healthy individuals in Korea.
AB  - Hwa-Byung (HB) is a Korean culture-bound psychiatric syndrome caused by the
      suppression of anger. HB patients have various psychological and somatic
      symptoms, such as chest discomfort, a sensation of heat, and the sensation of
      having an epigastric mass. In this study, we measured brain activity in HB
      patients and healthy individuals in response to affective facial stimuli. Using
      functional magnetic resonance imaging (fMRI), the current study measured neural
      responses to neutral, sad, and angry facial stimuli in 12 healthy individuals and
      12 patients with HB. In response to all types of facial stimuli, HB patients
      showed increased activations in the lingual gyrus and fusiform gyrus compared
      with healthy persons, but they showed relatively lower activation in the
      thalamus. We also found that patients with HB showed lower activity in response
      to the neutral condition in the right ACC than healthy controls. The current
      study indicates that the suppression of affect results in aberrant function of
      the brain regions of the visual pathway, and functional impairment in the ACC may
      contribute to the pathophysiology of HB.

PMID- 18609430
TI  - A long-term prospective study on the outcome of bipolar patients treated with
      long-acting injectable risperidone.
AB  - BACKGROUND: Risperidone is the first atypical antipsychotic to become available
      in a long-acting, injectable formulation. This is the first prospective study to
      assess the effectiveness of long-acting risperidone in a cohort of bipolar
      patients. METHODS: Twenty-nine DSM-IV acutely manic bipolar inpatients with a
      history of poor or partial adherence to medication entered the mirror-design
      observational study. They received naturalistic treatment for a manic episode
      plus long-acting, injectable risperidone for a mean period of 2 years. The
      following measures were used to assess the effectiveness of risperidone: the
      number of hospitalizations, the number of manic, mixed, and depressive episodes
      leading to hospitalization, the mean duration of hospitalizations, time to
      relapse, treatment adherence, aggression and suicide attempts. The Clinical
      Global Impressions (CGI) was used for clinical relevance as well. RESULTS: During
      the follow-up, there was a significant decrease in the number of hospitalizations
      per patient (Z-2.72 P < 0.006), in the number of manic or mixed episodes leading
      to hospitalization (Z-2.68 P < 0.007) but not in the hospitalizations due to
      depressive episodes, a decrease in the average length of hospitalization per
      patient (Z-3.27 P < 0.001), a significant increase in the time to any new episode
      (first relapse) (Z-3.28, P < 0.001), and significant improvements in treatment
      adherence (P < 0.0001) and hetero-aggressive episodes (P < 0.0001), but not
      suicide attempts (P = NS). At study endpoint 14 patients (48%) were very much
      improved according to the CGI. DISCUSSION: This observational long-term study
      provides support to long-acting injectable risperidone being effective for the
      maintenance treatment of mania and improving treatment adherence, reducing
      relapses and re-hospitalization rates.

PMID- 18609432
TI  - Functional magnetic resonance imaging of tics and tic suppression in Gilles de la
      Tourette syndrome.
AB  - Tics are defined as involuntary, quick, sudden, and stereotypical movements or
      phonic productions. Despite the fact that tic suppression plays an important role
      for the patient's ability to cope with tic disorders, investigations of the
      underlying neural correlates using functional imaging focused on tic generation
      rather than tic suppression. We examined a patient with Gilles de la Tourette
      syndrome with regard to neural mechanisms of tic generation and tic suppression
      using fMRI. Three different conditions were compared: "tics", "tics suppressed",
      and "tics imitated". The comparisons of "tics" to tics suppressed" and of "tics"
      to "tics imitated" showed similar activation in the anterior cingulate cortex.
      This leads to distinct suggestions concerning the neural network involved in tic
      suppression. Similar mechanisms may be involved in tic suppression via mental
      efforts or active movements.

PMID- 18609433
TI  - A case with occurring adverse effects when cross-over titration from fluvoxamine
      to paroxetine associated with increasing the plasma fluvoxamine level in major
      depressive disorder.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are first line drugs for treating
      not only depressive disorder but also anxiety disorder. Fluvoxamine, a SSRI, is
      mainly metabolized by cytochrome P450 (CYP) 2D6 and 1A2. However, paroxetine, an
      another SSRI is potent inhibitor for CYP 2D6. We report a case with depression
      whose plasma fluvoxamine level rapidly increased after the addition of paroxetine
      while switching from fluvoxamine to paroxetine. The case indicates that emerging
      adverse effects via the pharmacokinetic interaction of these drugs when switching
      patients from fluvoxamine to paroxetine can occur.

PMID- 18609434
TI  - Leukopenia and thrombocytopenia on adding aripiprazole to phenytoin.

PMID- 18609435
TI  - Neuropsychiatric-developmental model for the expression of tics, pervasive
      developmental disorder, and schizophreniform symptomatology associated with
      PANDAS.

PMID- 18609436
TI  - Non-fatal overdose of duloxetine in combination with other antidepressants and
      benzodiazepines.
AB  - The pharmaco-toxicological profile of duloxetine, a novel SNRI antidepressant, is
      still not completely known; in particular, intoxication cases have been scarcely
      studied. Here a duloxetine overdose case, in combination with other
      antidepressants and benzodiazepines, is reported and the chemical-clinical
      correlations discussed; this is probably the first detailed report of such a
      case. The patient referred to have ingested nine tablets of Cymbalta (more than
      500 mg of duloxetine) and high amounts of four other drugs (venlafaxine,
      trazodone, sertraline and clonazepam). The patient was dozy and confused and some
      electrolyte imbalances were found. After gastrolavage, toxicological analyses
      revealed high plasma levels of duloxetine (384 ng/ml) and low levels of the other
      supposedly involved drugs. The overdose resulted to be not fatal and the outcome
      was relatively benign, also thanks to the fast emergency assistance. This case
      suggests that clinicians should be alerted to the possibility of toxic effects
      caused by simultaneous overdoses of duloxetine and other antidepressants and that
      caution should be used when prescribing more than one of these drugs to patients
      at risk of suicide.

PMID- 18609437
TI  - Is anorexia nervosa a neuropsychiatric developmental disorder? An illustrative
      case report.
AB  - We propose the concept that anorexia nervosa is a neuropsychiatric developmental
      disorder. In support of the concept we present a case report of a 12-year-old
      girl with high functioning autistic disorder who developed Tourette syndrome and
      obsessive-compulsive disorder. She subsequently experienced a distinct onset of
      partial anorexia nervosa characterized by fear of gaining weight, body image
      distortions, food preference idiosyncrasies including avoidance of fat, dietary
      restriction, a pursuit of thinness, episodic self-induced vomiting, the missing
      of her menstrual cycles, and a 10% decrement in expected weight for height. She
      fell short of the required 15% decrement in expected weight for height to qualify
      for the full syndrome. Our case presentation emphasizes the longitudinal
      commonalities and symptomatic overlap of her multiple comorbidities. We discuss
      treatment approaches typically used with individuals with neuropsychiatric
      developmental disorders which might benefit higher functioning individuals with
      eating disorders. We conclude with examples of a neuropsychiatric developmental
      approach to generate a research agenda for anorexia nervosa.

PMID- 18609441
TI  - Smooth pursuit eye movement (SPEM) in patients with multiple complex
      developmental disorder (MCDD), a subtype of the pervasive developmental disorder.
AB  - OBJECTIVE: Multiple complex developmental disorder (MCDD) is a well-defined and
      validated behavioural subtype of pervasive developmental disorder-not otherwise
      specified (PDD-NOS) and is thought to be associated with a higher risk of
      developing a schizophrenic spectrum disorder. The question was addressed whether
      patients with MCDD show the same psychophysiological abnormalities as seen in
      patients with schizophrenia. METHOD: Smooth pursuit eye movement (pursuit gain
      and saccadic parameters) was measured in children with either MCDD (n=18) or
      autism (n=18), and in age- and IQ-matched controls (n=36), as well as in a group
      of adult patients with schizophrenia (n=14) and a group of adult controls (n=17).
      RESULTS: We found the expected effect of lower velocity gain and increased number
      of saccades in schizophrenic patients. Children with MCDD also showed a lower
      velocity gain compared to controls children. In contrast, velocity gain was
      similar in autistic subjects and controls. No differences for velocity gain were
      found in a direct comparison between MCDD and autism. Saccadic parameters were
      not significantly different from controls in either MCDD or autistic subjects.
      CONCLUSION: Children with MCDD, like schizophrenic adults, show a reduced
      velocity gain, which could indicate that schizophrenia spectrum disorders and
      MCDD share (at least to some degree) a common neurobiological background.

PMID- 18609443
TI  - Kleine-Levin syndrome in two subjects with diagnosis of autistic disorder.
AB  - Kleine-Levin syndrome (KLS) is a rare disease characterized by recurrent episodes
      of hypersomnia, cognitive and behavioural disturbances, compulsive eating and
      hypersexuality. The disease is predominantly described in typically developed
      adolescents. Here, we present two cases with the diagnosis of KLS and autistic
      disorder. The aim of this presentation is to illustrate the clinical expression
      and differential diagnosis of KLS in this group.

PMID- 18609444
TI  - Blood pressure changes during clozapine or olanzapine treatment in Korean
      schizophrenic patients.
AB  - BACKGROUND: Numerous reports have linked atypical antipsychotics, especially
      clozapine and olanzapine, to the development of cardiovascular risk factors. In
      this retrospective chart review study, we investigated the blood pressure changes
      in Korean schizophrenic inpatients treated with clozapine or olanzapine. METHOD:
      We reviewed the medical record of schizophrenic patients treated with clozapine
      or olanzapine for 8 weeks. A total of 167 patients were included in the study; 70
      patients in clozapine group and 97 patients in olanzapine group. Systolic and
      diastolic blood pressures prior to medication and at post-treatment (8-week) were
      assessed, and changes in blood pressure were analyzed. The prevalence of
      hypertension at the time of study period was assessed and compared between the
      two groups. RESULTS: There was a significant difference in hypertension
      prevalence in comparisons between the clozapine and olanzapine group. The
      systolic and diastolic blood pressures in the clozapine group were significantly
      increased after treatment, but systolic and diastolic blood pressures in
      olanzapine group did not change significantly. CONCLUSION: Our findings suggest
      that clozapine treatment may be associated with increased blood pressure and
      higher prevalence of hypertension, which may have a significant impact on medical
      morbidity and mortality.

PMID- 18609445
TI  - Winter/summer seasonal changes in malondialdehyde formation as a source of
      variance in oxidative stress schizophrenia research.
AB  - BACKGROUND: Malondialdehyde (MDA), an oxidative stress biological marker, is one
      of the most frequently used markers of lipid peroxidation in schizophrenia
      research. Data regarding MDA levels in schizophrenia are controversial. Our aim
      is to study the existence of winter/summer seasonal changes in serum MDA levels
      in schizophrenic patients. METHODS: Twenty-three clinically stable treated
      chronic paranoid schizophrenic outpatients were studied in summer and winter.
      Blood was sampled between 08:30 and 09:00 h. Serum MDA was determined by the
      thiobarbituric acid reactive substances technique. The clinical state was
      assessed by means of the Clinical Global Impression (CGI) scale. RESULTS: Mean
      serum MDA levels were significantly higher in summer than winter (2.49+/-0.25 vs.
      1.86+/-0.11 nmol/ml, P<0.03). Summer MDA was increased by a 33.9% compared to
      winter MDA. Age, gender, smoking status, body mass index, psychopharmacological
      treatment, illness duration, age of illness onset and CGI did not affect
      significantly MDA levels. CONCLUSION: Our results show that serum MDA presents a
      winter/summer rhythm of formation, with higher levels in summer than winter. It
      is strongly advisable to take into account the summer/winter variation in MDA
      levels when researching into this field.

PMID- 18609446
TI  - Involvement of stearoyl-CoA desaturase in the reduction of amidoxime prodrugs.
AB  - 1. This study investigates the enzymatic reduction of N-hydroxylated amidines by
      porcine adipose tissue and the possible involvement of stearoyl-CoA desaturase
      (SCD). 2. The reduction of the model substrate benzamidoxime was studied with
      porcine adipose tissue microsomes and partially purified SCD from SCD-enriched
      rat liver microsomes. 3. Inhibitor studies with these microsomal preparations
      using various inhibitors including anti-SCD antibody, cyanide and stearoyl-CoA
      supported a role for SCD in the reduction of N-hydroxylated amidines in adipose
      tissue. The content and activity of SCD in these microsomes was established by
      Western blot and SCD activity determinations. Additionally, a reconstituted
      system of cytochrome b(5), NADH-cytochrome b(5) reductase and partially purified
      SCD from SCD-enriched rat liver microsomes supported benzamidoxime reductase
      activity that was inhibitable by an anti-SCD antibody. 4. The results support the
      participation of SCD in the reduction of amidoxime prodrugs and demonstrate for
      the first time that SCD can also accept foreign compounds (xenobiotics) as
      substrates.

PMID- 18609447
TI  - In vitro metabolism of a novel PPAR gamma agonist, KR-62980, and its
      stereoisomer, KR-63198, in human liver microsomes and by recombinant cytochrome
      P450s.
AB  - 1. KR-62980 and its stereoisomer KR-63198 are novel and selective peroxisome
      proliferator-activated receptor gamma (PPAR gamma) modulators with activity
      profiles different from that of rosiglitazone. This study was performed to
      identify the major metabolic pathways for KR-62980 and KR-63198 in human liver
      microsomes. 2. Human liver microsomal incubation of KR-62980 and KR-63198 in the
      presence of a beta-nicotinamide adenine dinucleotide phosphate (NADPH)-generating
      system resulted in hydroxy metabolite formation. In addition, the specific
      cytochrome P450s (CYPs) responsible for KR-62980 and KR-63198 hydroxylation were
      identified by using a combination of chemical inhibition in human liver
      microsomes and metabolism by recombinant P450s. It is shown that CYP1A2, CYP2D6,
      CYP3A4, and CYP3A5 are the predominant enzymes in the hydroxylation of KR-62980
      and KR-63198. 3. The intrinsic clearance through hydroxylation was consistently
      and significantly higher for KR-62980 than for KR-63198, indicating metabolic
      stereoselectivity (CL(int) of 0.012 +/- 0.001 versus 0.004 +/- 0.001 microl min(
      1) pmol(-1) P450, respectively). 4. In a drug-drug interaction study, KR-62980
      and KR-63198 had no effect on the activities of the P450s tested (IC(50) > 50
      microM), suggesting that in clinical interactions between KR-62980 and KR-63198
      the P450s tested would not be expected.

PMID- 18609448
TI  - Characterization of renal tubular apical efflux of zonampanel, an alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate receptor antagonist, in humans.
AB  - 1. Zonampanel, a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate
      (AMPA) receptor antagonist, is mainly excreted unchanged via renal tubular
      secretion. The renal apical transport transport of zonampanel was examined in
      this study using HEK293 cells expressing human organic anion transporter 4
      (OAT4/SLC22A11), and membrane vesicles prepared from Sf-9 insect cells expressing
      human multidrug resistance-associated protein 2 (MRP2/ABCC2), MRP4 (ABCC4), and
      breast cancer resistance protein (BCRP/ABCG2). 2. Glutaric acid, a model
      dicarboxylate, trans-stimulated the uptake of [(14)C]zonampanel by OAT4,
      suggesting that zonampanel was transported by OAT4 via an exchange with
      dicarboxylate. Considering the endogenous dicarboxylate gradient, OAT4 seems to
      transport zonampanel in the direction of reabsorption rather than secretion. For
      MRP2, MRP4, and BCRP, zonampanel selectively inhibited the activity of MRP4 (K(i)
      = 41.3 microM). Marked transport of [(14)C]zonampanel was observed only for MRP4
      (K(m) = 33.7 microM). 3. In conclusion, the data indicate that MRP4 was the
      apical efflux transporter that contributed to the active renal tubular secretion
      of zonampanel in humans, in concert with the apical reabsorption transporter OAT4
      and basolateral uptake transporters.

PMID- 18609449
TI  - In vivo confocal laser endomicroscopy of the human liver: a novel method for
      assessing liver microarchitecture in real time.
AB  - BACKGROUND AND STUDY AIMS: Confocal endomicroscopy is a unique novel tool for in
      vivo histology in humans. Due to limitations imposed by the form of the equipment
      and by sterilization workflows, its use has been limited to the gastrointestinal
      tract so far. We have developed a rigid miniaturized probe for confocal
      endomicroscopy of the human liver during laparoscopy. PATIENTS AND METHODS: To
      assess the feasibility and potential clinical value of this new system (diameter
      6.3 mm), 25 patients with liver disease were examined during routine
      minilaparoscopy under conscious sedation. RESULTS: Subsurface serial images (from
      surface to 250 microm) were generated in real time after fluorescein injection,
      permitting visualization of hepatocytes, bile ducts, sinusoids, and collagen
      fibers in vivo. Typical appearances of liver diseases were identified. Confocal
      diagnosis of moderate-to-severe steatosis and pericellular fibrosis correlated
      well with histopathologic analysis of subsequent biopsies (83.3 % and 84.6 %,
      respectively). In addition, intra-abdominal structures such as gallbladder,
      omentum, and stomach were analyzed by endomicroscopy. CONCLUSIONS: A miniaturized
      imaging system for confocal laparoscopy allowed in vivo microscopic analysis of
      healthy and diseased human liver for the first time during ongoing
      minilaparoscopy. Although such in vivo imaging does not yet compete with
      conventional histopathology, this novel confocal laparoscopy system may be of
      future relevance for immediate morphodynamic analysis in liver disease and the
      targeting of biopsies in vivo.

PMID- 18609450
TI  - NOTES transvaginal video-assisted cholecystectomy: first series.
AB  - BACKGROUND AND STUDY AIMS: Extensive research has been conducted to develop
      natural-orifice transluminal endoscopic surgery (NOTES) as a new approach to less
      invasive surgery. Our aim is to present the technique and initial prospective
      results of a transvaginal video-assisted laparoscopic approach to NOTES
      cholecystectomy in order to perform minimally invasive surgery without visible
      scars. PATIENTS AND METHODS: From July 2007 to March 2008, 32 women underwent
      transvaginal video-assisted laparoscopic cholecystectomy using a transvaginal 10
      mm 45 degrees rigid bariatric optic through a 12-mm bariatric trocar and two
      abdominal trocars (2-mm and 5-mm). Data on the history, surgical time,
      complications, and recovery were recorded prospectively in each case. RESULTS:
      Mean age was 33 years (range 22 - 47 years); mean body mass index was 29 (range
      20 - 42). Mean operative time was 38 minutes (range 18 - 50 minutes). Patients
      were discharged 6 hours after the procedure without the need for pain medication
      in the following days and returned to normal working activities within 24 hours
      of the procedure. CONCLUSIONS: Transvaginal video-assisted NOTES cholecystectomy
      seems to be an efficient and safe approach to minimally invasive surgery,
      providing patients with a comfortable recovery with virtually no abdominal scars
      as a bridge to exclusively NOTES procedures.

PMID- 18609451
TI  - How do gynecologists feel about transvaginal NOTES surgery?
AB  - BACKGROUND: Natural-orifice transluminal endoscopic surgery (NOTES) is regarded
      as safer and less invasive than laparoscopic surgery. However, there has been no
      documentation of the opinions of surgically active, experienced gynecologists
      about the indications, contraindications, risks, and complications of
      transvaginal access. METHODS: A two-page questionnaire was distributed to the
      heads of the gynecological departments at 181 university and major teaching
      hospitals across Germany, Austria, and Switzerland. Fifty-two questionnaires
      (28.7 %) were returned and evaluated. The questionnaire contained ten questions,
      four of which were yes/no questions and another five of which allowed between
      four and seven answers. The questionnaire contained one additional open question.
      RESULTS: Of the respondents, 69.2 % classified transvaginal access for
      extrapelvic abdominal surgery as ethical; the remaining 30.8 % described it as
      experimental. Only 28.8 % would recommend NOTES to their patients if NOTES
      presented the same surgical risks as the laparoscopic approach. When asked about
      NOTES-associated complications, 73.1 % mentioned the risk of infection, 61.5 %
      visceral lesions, 44.2 % infertility, and 34.6 % adhesions. In terms of long-term
      problems, gynecologists are concerned about dyspareunia and infertility. Adopting
      their patients' point of view, 17.3 % voted the lack of scarring compared to
      laparoscopy as important and 57.6 % as unimportant. CONCLUSIONS: While
      transvaginal NOTES is argued to be a promising access for scarless surgery,
      gynecologists mention postoperative infection, visceral lesions, infertility, and
      adhesions as conceivable complications. Since long-term experience has not yet
      been achieved, potential problems such as dyspareunia, infertility, and the
      spread of pre-existing endometriosis remain definitely conceivable complications.

PMID- 18609452
TI  - Cosmetic issues of abdominal surgery: results of an enquiry into possible grounds
      for a natural orifice transluminal endoscopic surgery (NOTES) approach.
AB  - BACKGROUND AND STUDY AIMS: Decreased scarring is an advantage of minimally
      invasive surgery. The new experimental technique of natural orifice transluminal
      surgery (NOTES) aims at totally scarless surgery. We examined the general
      attitudes of patients and unaffected persons towards scarless surgery. METHODS
      AND PARTICIPANTS: We used a 7-item questionnaire in structured interviews with
      hospital visitors, following detailed standardized explanation of terms used and
      of possible complications, to groups of 10 participants, during an "open ward"
      day. A visual analog scale (VAS) from 1 (none) to 10 (very much) was used for all
      but one item. Questions concerned the importance of cosmetic results in abdominal
      surgery, satisfaction regarding existing scars, hypothetical acceptance of
      increased risk as a trade-off for the absence of scars, and other issues. Data
      were analyzed for participants overall, and for three age groups and both sexes.
      RESULTS: 292 participants (male : female 1 : 1; mean age 43 years) completed the
      questionnaire. Cosmetic issues were rated as important (median 8), but acceptance
      of existing scars was also high in those affected (median 8, n=68). Approval of
      scarless surgery decreased with a presumed risk increase (from score 9 down to
      score 5), and overall an increase in risk of 10 % was judged to be acceptable as
      a trade-off for total absence of scarring. Younger people tended to be less
      satisfied with scars, but were also less inclined than older people to accept
      higher surgical risk in this hypothetical context. CONCLUSIONS: People generally
      seem to favor scarless abdominal surgery, even with some increase in risk.

PMID- 18609453
TI  - Endoscopic colotomy closure after full thickness excision: comparison of T
      fastener with multiclip applier.
AB  - BACKGROUND AND STUDY AIMS: Safe, reliable, and efficient endoscopic closure of a
      colotomy is paramount for endoscopic full thickness excision of the colon. Two
      newly developed devices, the Tissue Apposition System (TAS) and the InScope Multi
      Clip Applier (IMCA), may help to achieve this. The aim of this study was to
      determine the feasibility of using each device to close colotomies after full
      thickness wall excisions. MATERIAL AND METHODS: 12 pigs were used in the study.
      After laparoscopic full thickness excision of the colonic wall, the defect was
      closed using either the TAS or the IMCA. Closure was performed under laparoscopic
      vision. Success of colotomy closure, time taken for colotomy closure,
      postoperative infections, and complication rates were recorded. RESULTS: Complete
      closure was achieved in 6/6 pigs in the TAS group. In 5/6 pigs in the IMCA group
      closure was successful; in one pig laparoscopic assistance was used. Median
      closure time (range) was significantly lower in the TAS group at 48 minutes (15 -
      51) vs. 76 minutes (43 - 145) in the IMCA group. There were no postoperative
      infections or complications. CONCLUSIONS: Endoscopic closure after full thickness
      colonic wall excision is feasible with both the TAS and the IMCA. Closure times
      are significantly shorter and handling is easier with the TAS. Combined use of
      both systems might be beneficial.

PMID- 18609454
TI  - Collagenous colitis: a case series with confocal laser microscopy and histology
      correlation.
AB  - Confocal laser endomicroscopy (CLE) was carried out in seven patients with
      chronic watery diarrhea (three men; age range 68 - 84 years) to find the
      correspondence between CLE and histological findings in collagenous colitis. On
      the basis of the CLE images, two to five biopsies were performed in various
      segments of the colon. The endoscopic and histological diagnoses of collagenous
      colitis were made blindly. The quality of the CLE images was quantified from 0
      (the endoscopist could not visualize the corresponding histologic equivalent) to
      3 (the endoscopist could identify >or= 80 % of the corresponding histologic
      equivalent). Four out of seven patients had histological findings of collagenous
      colitis. Correspondence between histology and CLE images yielded the following
      scores: 3 for epithelial architecture, 3 for goblet cells, 3 for vessels, and 2
      for inflammatory infiltrate. In collagenous colitis patients, CLE identified a
      well-defined "shell" around the crypts, corresponding to the increase in the
      thickness of the subepithelial collagenous plate evidenced by histology. CLE
      appears to be a promising means of identifying typical collagenous colitis
      features.

PMID- 18609455
TI  - The safety of fine-needle aspiration guided by endoscopic ultrasound.

PMID- 18609457
TI  - Electrolyzed acid water can cause colitis?

PMID- 18609460
TI  - Portuguese Society of Digestive Endoscopy: recommendations for endoscopic mucosal
      resection.

PMID- 18609462
TI  - [Therapy of community acquired pneumonia].

PMID- 18609463
TI  - [Tonsillotomy with bipolar coagulation scissors].
AB  - BACKGROUND: Nowadays, tonsillotomy is an accepted operating procedure for the
      diagnosis of tonsillar hyperplasia in small children. Up to now many different
      techniques such as laser, radiofrequency, coblation or micro-debrider have been
      used. In this study, for the first time bipolar coagulation scissors were
      utilized. METHODS: Up to December 2006, a total of 91 children with benign
      tonsillar hyperplasia were tonsillotomized by bipolar coagulation scissors. Of
      these 91 children, 38 (average age 74 months) were recruited for this study. Pre
      operative and post-operative complaints were documented and the success of the
      operation was evaluated by the parents. RESULTS: In more than 90 % of the
      children, pre-operative complaints had disappeared completely after surgery. The
      operation was considered by all parents to have been very helpful. With no child
      did re-tonsillotomy or tonsillectomy have to be performed in the observation
      interval, which was a maximum of three years. CONCLUSION: Tonsillotomy with the
      bipolar coagulation scissors is a reliable method of surgery in children with
      tonsillar hypertrophy. This type of scissors offers an ideal combination of
      dissection and coagulation. From an economic point of view, the bipolar
      coagulation scissors offer a clear advantage over laser.

PMID- 18609464
TI  - EUS for portal hypertension: a comprehensive and critical appraisal of clinical
      and experimental indications.
AB  - Endoscopic ultrasonography (EUS) has significantly improved our understanding of
      the complex vascular structural changes that occur in portal hypertension and
      their clinical and prognostic significance. EUS in combination with color Doppler
      technique enables us to study the hemodynamic changes in the portal venous system
      noninvasively, and to determine objectively the effect of different
      pharmacological agents on portal hypertension. EUS has also found some role in
      the treatment and follow up of esophageal and gastric varices. It may play a
      clinical role in the diagnosis of gastric, duodenal, and rectal varices. Recently
      reported EUS-based devices that measure variceal wall tension and intravariceal
      pressure noninvasively could have an impact on the identification of patients at
      high risk of variceal bleeding with the aim of initiating prophylactic treatment,
      and in the assessment of patients' responses to drug therapy of portal
      hypertension. EUS is occasionally very helpful in the clinical management of
      portal hypertension. It is an interesting and important research tool for many
      experimental indications that are not routinely applied in clinical practice at
      this time.

PMID- 18609465
TI  - Colonoscopy is the preferred colorectal cancer screening method in a population
      based program.
AB  - BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC)
      are promoted by professional societies; however, few data are available about the
      factors that determine patient participation in screening, which is crucial to
      the success of population-based programs. This study aimed (i) to identify
      factors that determine acceptance of screening and preference of screening
      method, and (ii) to evaluate procedure success, detection of colorectal
      neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND
      METHODS: Following a public awareness campaign, the population aged 50 - 80 years
      was offered CRC screening in the form of annual fecal occult blood tests,
      flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731
      asymptomatic persons (12.0 % of the target population) registered with and were
      eligible to take part in the screening program. Access to information and a
      positive attitude to screening were major determinants of participation.
      Colonoscopy was the method preferred by 74.8 % of participants. Advanced
      colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and
      increased with age. Significant complications occurred in 0.5 % of those
      undergoing colonoscopy and were associated with polypectomy or sedation. Most
      patients were satisfied with colonoscopy and over 90 % would choose it again for
      CRC screening. CONCLUSIONS: In this population-based study, only a small
      proportion of the target population underwent CRC screening despite an extensive
      information campaign. Colonoscopy was the preferred method and was safe. The
      determinants of participation in screening and preference of screening method,
      together with the distribution of colorectal neoplasia in different demographic
      categories, provide a rationale for improving screening procedures.

PMID- 18609466
TI  - External lacrimal punctum grading: reliability and interobserver variation.
AB  - PURPOSE: To test the reliability and interobserver variation of external lacrimal
      punctum (ELP) grading. METHODS: In a population-based epidemiologic study, ELP
      was visually graded based on slit lamp examination (grade 0 to 5), as described
      previously. Grades 0, 1, and 2 are for closed or stenotic ELP and grade 3 is for
      normal ELP (subjective grades). Grades 4 and 5 are for larger than normal (slit)
      ELP measured in millimeters by slit lamp beam (objective grades). Upper and lower
      ELP were graded by an oculoplastic surgeon and a senior ophthalmology resident.
      Both observers were masked to the reading of the other. Both observers were
      familiar to the grading system for past few years, although the oculoplastic
      surgeon had more experience in this regard. Patients with previous periocular
      surgery, medial lid mass obscuring the ELP, anatomically distorted punctum, and
      subjects with grade 4 and 5 ELP (objective grades) were excluded. The intraclass
      correlation coefficient test was used for the statistical analysis. RESULTS:
      There were 632 eyes from 174 (55.10%) male and 142 (44.90%) female subjects.
      Subjects' ages ranged from 7 to 87 years (mean +/- SD = 54+/-17.56). The
      intraclass correlation coeficient test showed a positive and strong correlation
      between two observers for grading the upper (value=+0.87, 95% CI: 0.84 and 0.88,
      p=0.000) and lower (value=+0.91, 95% CI: 0.90 and 0.92, p=0.000) ELP. In general,
      the less experienced observer tended to overestimate both upper and lower ELP
      grading. CONCLUSIONS: Reliability of the new ELP grading makes it a recommendable
      option for use in the clinic and comparing reports on ELP pathologies.

PMID- 18609467
TI  - Effect of topical netilmicin on the reduction of bacterial flora on the human
      conjunctiva.
AB  - PURPOSE: To investigate the effects of topical netilmicin on human conjunctival
      bacterial flora. METHODS: Fifty-six patients' eyes with cataract were treated
      three times a day with netilmicin 1 day before the surgery. The fellow eyes of
      the patients were not treated. After 1 day of netilmicin application cultures of
      the inferior palpebral conjunctiva were performed in both eyes. Bacterial
      evaluation is qualitative. McNemar test was used for statistical analyses.
      RESULTS: The number of eyes with positive culture for coagulase negative
      staphylococcus (CNS) in untreated eyes was 43 (76.8%) and in treated eyes it was
      5 (8.93%) and the difference was statistically significant (p=0.000). In
      untreated eyes number of negative cultures with no bacterial growth was 8 (14.3%)
      and it was 47 (83.9%) in the treated eyes. The difference among groups was
      statistically significant (p=0.000). Netilmicin is found very effective for CNS
      as the percentage of positive cultures (n=43) in untreated eyes to positive
      cultures (n=4) in the treated fellow eye was 90.7%. Likewise, all patients with
      Staphylococcus aureus positive cultures in untreated eyes (n=5) had negative
      culture for this microorganism in their treated fellow eyes (100%). CONCLUSIONS:
      The Endophthalmitis Vitrectomy Study demonstrated that the most common causes of
      postoperative endophthalmitis are coagulase negative microorganisms, S aureus and
      Streptococcus species. As netilmicin was found effective to reduce the number of
      positive cultures for these bacteria, it can be used to lower the incidence of
      postoperative endophthalmitis before surgery.

PMID- 18609468
TI  - Evaluation of therapeutic deep anterior lamellar keratoplasty in acute ocular
      chemical burns.
AB  - PURPOSE: To evaluate the role of deep anterior lamellar keratoplasty (DALK) in
      acute ocular chemical burns. METHODS: The study was conducted in 50 eyes of 50
      patients (24 male, 26 female) with average age of 38.3+/-14.3 years. DALK in 5
      eyes (10%), DALK with quadrant conjunctivo-limbal graft in 25 eyes (50%), and
      DALK with amniotic membrane in 20 eyes (40%) were performed along with
      conventional medical therapy. Controls who were matched in all respects (50 eyes)
      were given medical therapy only as they refused surgical intervention. RESULTS:
      Follow-up of cases ranged from 6 to 48 months (mean 21.5+/-14.18 months). Forty
      three eyes (86%) could be restored with clear cornea as compared to 6% in control
      group. The visual acuity improvement was seen in 100% with good score (0.49+/
      1.46) in DALK group as compared to 18% with low score (0.03+/-0.01) in control
      group (p<0.0001). Visual acuity improvement in DALK was 6/12 in 19 eyes (38%),
      6/24 in 28 eyes (56%), and 6/36 in 3 eyes (6%) but was 3/60-6/60 in 6 eyes (12%)
      and finger counting only in 3 eyes (6%) in control group. Eyes with advanced
      grade II and grade III showed better improvement than those with burns of grade
      IV (p<0.05). The discomfort was relieved and epithelial healing was achieved
      immediately in DALK as compared to a prolonged course in control group
      (p<0.0001). Vascularization presented in 38% in DALK with least score (0.13+0.15)
      as compared to 100% in control group with high score (2.8+/-0.30). Perforation of
      cornea was seen only in 2 cases (4%) in DALK with low score (0.03+/-0.10) as
      compared to 88% in control group (1.33+/-0.20). Symblepharon was seen in 2% in
      DALK group as compared to 62% in control group. CONCLUSIONS: DALK with and
      without conjunctival or amniotic membrane transplantation is an effective
      technique in restoring the integrity of the eye with an excellent graft
      transparency in 86% and improvement in visual acuity in 100% of the acute
      chemical burns.

PMID- 18609469
TI  - Bedside glue blepharorrhaphy for recalcitrant exposure keratopathy in immobilized
      patients.
AB  - PURPOSE: To report the practical use and the effectiveness of cyanoacrylate glue
      blepharorrhaphy in immobilized patients with recalcitrant exposure keratopathy.
      METHODS: Retrospective case series. Temporal two thirds of upper eyelid eyelashes
      were glued to lower eyelid skin with tissue adhesive n-butyl-2-cyanoacrylate
      (histoacryl blue) after application of a contact lens. The systemic condition for
      immobilization; duration of exposure signs in the ocular surface; location,
      depth, and dimensions of the corneal ulcer; duration of effective
      blepharorrhaphy; and the time to heal were recorded. RESULTS: Twelve eyes of nine
      patients were treated. The reasons for immobilization were coma due to malignancy
      (3 patients), ischemic encephalopathy (2 patients), subarachnoid hemorrhage (2
      patients), head trauma (1 patient), coma and hypotony of unknown cause (1
      patient). All of the corneal ulcers healed within 4 to 11 days (mean: 5.5 days).
      Blepharorrhaphy opened spontaneously in 4 to 21 days (mean: 8.6 days).
      CONCLUSIONS: Bedside glue blepharorrhaphy with tissue adhesive n-butyl-2
      cyanoacrylate is a practical, economic, and effective procedure in the treatment
      of exposure keratopathy in immobilized patients.

PMID- 18609470
TI  - Ultrasound biomicroscopic measurement of anterior chamber biometry between before
      and after pupil dilation in children.
AB  - PURPOSE: To evaluate anterior chamber biometry of the eyes of normal children
      using ultrasound biomicroscopy (UBM) and to evaluate the differences in biometry
      between children and adults, and before and after pupil dilation in children.
      METHODS: Anterior chamber depth (ACD) and trabecular-iris angle (TIA) were
      measured in 94 normal children and 15 normal adults using UBM. Before and after
      pupil dilation were measured in 42 children with emmetropic and hyperopic eyes.
      RESULTS: In 66 emmetropic children, ACD and TIA were 2.93+/-0.18 mm and 34.42+/
      4.02 degrees, respectively. In 28 hyperopic children, ACD and TIA were 2.92+/
      0.21 mm and 35.05+/-4.42 degrees, respectively. There was no significant
      difference in anterior chamber biometry associated with the refraction. ACD did
      not differ between children and adults, but TIA in children was wider than in
      adults. There was no significant difference in ACD or TIA before versus after
      pupil dilation in any case. CONCLUSIONS: Anterior chamber biometry in children
      showed no differences before and after pupil dilation. Also, there was no
      difference in ACD of children as compared to adults; however, TIA in children was
      significantly wider than in adults.

PMID- 18609471
TI  - Strabismus in developmental cataract.
AB  - PURPOSE: To evaluate the presence of strabismus in patients with developmental
      cataract rendered pseudophakic and how this influences their visual acuity.
      METHODS: A retrospective study was carried out on 113 patients with developmental
      cataract who came under the authors' observation at the outpatient department of
      the Pediatric Ophthalmology Unit of the University of Federico II of Naples from
      1990 to 2005. All patients were followed up for a long period (mean 62 months,
      range 36-144 months). Age at diagnosis, sex, laterality, age at cataract
      extraction, morphology, and cataract density were all considered as possible
      factors associated with strabismus. Visual acuity and ocular motility before and
      after cataract extraction surgery were especially noted. Statistical evaluation
      was performed using t-test, Chi-square test, and Fisher exact test. RESULTS: Out
      of the 113 patients a total of 181 eyes were affected: 68 patients (60%)
      presented bilateral cataract, 45 patients (40%) monolateral cataract. Strabismus
      was present in 39 patients (34%) before cataract surgery. Age at cataract
      diagnosis, age at surgery, sex, and cataract morphology were not found to be
      statistically associated with strabismus. However, laterality was found to be
      statistically associated with the onset of strabismus. Cataract density was found
      to be statistically associated with poor vision. Patients with strabismus
      presented a non statistically significant lower visual acuity. CONCLUSIONS:
      Strabismus has a greater incidence in developmental cataract compared to the
      general population, and can influence visual acuity, especially in monolateral
      and total cataracts. Intraocular lens implants produced satisfactory visual
      rehabilitation.

PMID- 18609472
TI  - A study on the awareness of cataract disease and treatment options in patients
      who need surgery in a rural area of Eastern China.
AB  - PURPOSE: To investigate the awareness of cataract disease and treatment and to
      determine the major barriers for patients who need cataract treatment in a rural
      area of eastern China. METHODS: A total of 251 cataract patients were selected by
      means of eye disease screenings throughout Jiangyan County. Questionnaires were
      administered after the doctor determined that the patient needed cataract
      surgery. The patient's awareness questionnaire was developed by Fletcher and
      clinically validated at the Aravind Eye Hospital in India. RESULTS: A total of
      89.6% of patients had been aware of their condition for more than 1 year. Only
      49.8% of all patients had known for more than 1 year that their eye disease could
      be treated. The major barriers for those seeking eye treatment included residual
      functional vision (49.0%), financial problems (36.7%), no demand for the
      operation (8.8%), and skepticism about the operation (8.8%). Poor vision function
      grade and female gender were two significant factors associated with a longer
      awareness (>3 years) of the existence of cataracts. Patients with a history of
      eye disease and a longer awareness of eye disease were more likely to have known
      about the potential treatments for a longer period of time (>1 year).
      CONCLUSIONS: The patients' awareness of the presence of cataract disease and
      potential treatment were unbalanced. The main treatment barriers were lower
      demand for vision improvement and financial problems. It is imperative to educate
      patients on eye health care and to provide low cost, but high quality, cataract
      surgery to these patients.

PMID- 18609473
TI  - Systemic associations and prevalence of exfoliation syndrome in patients
      scheduled for cataract surgery.
AB  - PURPOSE: To study the frequency of exfoliation syndrome (XFS) and its association
      with intraocular pressure (IOP) and systemic diseases in patients with age
      related cataract scheduled for surgery. METHODS: All 1480 cataract patients had a
      comprehensive systemic and eye examination, including slit-lamp biomicroscopy
      before and after mydriasis, IOP measurement, gonioscopy, and fundus examination.
      RESULTS: The percentage of XFS among patients scheduled for cataract surgery was
      16.4, with no gender difference (p=0.833). The mean age of XFS patients (74.3+/
      7.0 years) was significantly higher when compared to the ones without XFS (66.5+/
      10.9 years) (p<0.001). XFS was unilateral in 41.3% of the subjects and bilateral
      in 58.7%. The number of subjects with XFS increased significantly with aging
      (p<0.001) (OR=1.093, 95% CI=1.073-1.14) (p<0.001). The most common type of
      cataract was nuclear in the XFS group (33.5%) and 24.6% of patients with mature
      cataract had XFS. In the XFS group, 11.2% of the subjects had glaucoma, which was
      statistically higher than the non-XFS group (4.6%) (p<0.001) (OR=2.67, 95%
      CI=1.65-4.32). Eighty-four patients had glaucoma and 27 of them (32.1%) had
      exfoliative glaucoma. The only systemic disease that was found to be associated
      with XFS was coronary heart disease with an OR of 1.49 (95% CI=1.068-2.072)
      (p=0.019). CONCLUSIONS: XFS is a common problem in the aging cataract population
      of Turkey and increased IOP, glaucomatous optic neuropathy, and coronary heart
      disease occur more frequently in patients with XFS compared with subjects without
      XFS.

PMID- 18609474
TI  - Comparison of daytime efficacy and safety of dorzolamide/timolol maleate fixed
      combination versus latanoprost.
AB  - PURPOSE: To compare the 12-hour efficacy and safety of dorzolamide/timolol fixed
      combination (DTFC) dosed twice daily versus latanoprost dosed every evening
      following a timolol run-in in primary open-angle glaucoma patients. METHODS:
      Following a 6-week timolol run-in patients were randomized to either DTFC or
      latanoprost for 6 weeks and then changed to the opposite treatment for 6 weeks.
      At the end of the run-in, and the end of each treatment period, the intraocular
      pressure (IOP) was measured every 2 hours between 8:00 AM and 8:00 PM. RESULTS:
      Thirty-one patients completed at least one time point in both treatment periods.
      Both treatments reduced the IOP for the diurnal curve, and at each time point,
      from the timolol run-in baseline (p<0.0001). The 12-hour IOP on timolol was
      22.1+/-2.8 mmHg, whereas on DTFC it was 18.1+/-2.8 and latanoprost 18.3+/-3.1
      mmHg (p=0.4). Further, there was no statistical difference in IOP between
      treatments at any time point (p< or =0.1). There was no statistical difference
      for any individual adverse event between treatments (p>0.05). CONCLUSIONS: This
      study suggests that following a timolol run-in both DTFC and latanoprost provide
      comparable daytime efficacy and safety.

PMID- 18609475
TI  - Ocular inflammatory signs observed in a cohort of Spanish patients with Behcet
      disease and ocular inflammation.
AB  - PURPOSE: To study the clinical characteristics of a cohort of Spanish patients
      diagnosed with Behcet disease and who also presented ocular inflammation.
      METHODS: Thirty cases of Behcet disease were studied retrospectively. The authors
      studied age distribution, distribution by sex, clinical course, laterality, type
      of uveitis, secondary glaucoma, corneal involvement, hypopyon, iris-lens
      synechiae, secondary cataract, cystoid macular edema (CME), and papillitis (optic
      neuritis). RESULTS: Fourteen of the patients were men and 16 were women (ratio
      0.875:1). The mean age of the patients was 35.24 years (+/-10.917; 21-61 years).
      In 23 patients, the disease course was recurrent. In 9 patients, the disease
      manifested unilaterally. In 5 patients showing unilateral onset, the
      contralateral eye became affected. In 2 of the 30 patients, uveitis exclusively
      affected the anterior segment. In 8 patients, uveitis was solely posterior. There
      was one case of intermediate uveitis. The remaining 19 patients showed
      panuveitis. Three had focal chorioretinitis. One had diffuse chorioretinitis.
      Fifteen showed signs of diffuse vasculitis. Eight patients showed focal
      vasculitis. CONCLUSIONS: Women were slightly more affected than men, although the
      authors found no significant correlation between sex and the clinical variables
      examined. Apart from one unexpected case of intermediate uveitis, the
      observations are similar to those reported for other patient series.

PMID- 18609476
TI  - Primary intraocular lymphoma: another great masquerader.
AB  - PURPOSE: To describe diverse and atypical presentations of the most common
      masquerader in neoplastic masquerade syndromes. METHODS: Retrospective
      interventional case series. The authors identified three patients who presented
      with atypical and diagnostically challenging masquerading manifestations. These
      patients were eventually found to have primary intraocular lymphoma (PIOL). Their
      case histories, presenting signs and symptoms, diagnostic tests, and treatments
      are described. RESULTS: Patient 1 masqueraded as viral retinitis and branch
      retinal vein occlusion but was resistant to 5 weeks of oral and intravenous
      acyclovir. Patient 2 presented with choroidal infiltrates and vision loss. This
      patient had had breast carcinoma for the last 25 years and secondary metastasis
      was suspected. Patient 3 had chronic uveo-retinitis and a chronic
      Propionibacterium acnes infection was suspected. All three patients were
      diagnosed with PIOL. CONCLUSIONS: PIOL is an aggressive masquerader and not only
      presents clinical diagnostic difficulties but also requires expert tissue
      handling and analysis, so that early diagnosis can be made and therapy can be
      instituted.

PMID- 18609477
TI  - Four years incidence of diabetic retinopathy and effective factors on its
      progression in type II diabetes.
AB  - PURPOSE: To study the 4 years incidence of diabetic retinopathy in patients with
      type II diabetes and effective factors on its progression. METHODS: Among
      diabetic patients referred to Yazd Diabetes Research Center, 120 patients with
      type II diabetes without diabetic retinopathy were selected. After complete
      ophthalmic examination, fasting blood sugar (FBS), postprandial blood sugar,
      triglyceride, and cholesterol were measured and height, weight, and blood
      pressure (BP) were recorded. Then patients were followed with eye examination
      yearly for 4 years. RESULTS: Four-year cumulative incidence of diabetic
      retinopathy was 47.5% (95% CI: 38.6-56.4). The retinopathy was mild
      nonproliferative diabetic retinopathy (NPDR) in 43 (35.8%) whereas 10 (8.3%)
      patients had moderate NPDR, 3 (2.5%) patients had severe NPDR, and only one
      patient had proliferative diabetic retinopathy. The incidence of diabetic
      retinopathy was 5.8% in first year, 20.3% in the second year, 24.4% in the third
      year, and 7.4% in the fourth year. Duration of diabetes, FBS, and systolic BP had
      statistically significant relation with grades of diabetic retinopathy. However,
      there was no significant association between age, sex, body mass index,
      triglyceride, cholesterol, method of treatment, smoking, and diastolic BP with
      grades of diabetic retinopathy. CONCLUSIONS: These data provide 4-year cumulative
      incidence of diabetic retinopathy in defined type 2 diabetic patients. The
      present study shows that duration of diabetes, hyperglycemia, and systolic BP
      appear to be the major factors associated with the development of any level of
      retinopathy in type 2 diabetic patients.

PMID- 18609478
TI  - Diffuse retinal pigment epitheliopathy among the inhabitants of Brahmaputra
      Valley of India.
AB  - PURPOSE: To analyze the patient demography and the various fluorescein
      angiography (FA) features of diffuse retinal pigment epitheliopathy (DRPE) cases
      among the inhabitants of the Brahmaputra Valley of India and to see if there is
      any ethnic variation in its clinical presentation and risk factors. METHODS: This
      is a retrospective study in a clinical practice setting with study population of
      Aryan and Mongoloid races. Data analysis of 30 cases (40 eyes) of DRPE of 262
      consecutive cases of central serous chorioretinopathy (CSC) was done. The various
      features of these cases were compared and statistically evaluated with the
      findings of CSC cases with symptom duration of 6 months or more and cases with
      recurrent episodes. RESULTS: A total of 11.45% had DRPE that had average symptom
      duration of 3.50 years. Logistic regression showed high risk for DRPE if sensory
      retinal detachment (SRD) persists for more than 18 months. Systemic hypertension
      was another significant risk factor, whereas multiple RPE leaks appeared to be
      weakly significant. DRPE was predominant in eyes of patients having first acute
      episode of CSC in later age and fairly large retinal pigment epithelial
      detachments (PEDs) contributed to its development. Role of exogenous
      corticosteroid, retinotoxic drugs, and tobacco consumption could not be assessed
      properly due to inadequate sample size. CONCLUSIONS: The main factor for the
      development of DRPE is the persistence of SRD for more than 1.50 years. Fairly
      large leaking PED and onset of primary CSC in later age appear to contribute
      towards its development. Except for these, no major variation from Western
      studies was observed.

PMID- 18609479
TI  - Characterization of idiopathic macular telangiectasia type 2 by fundus
      fluorescein angiography in Indian population.
AB  - PURPOSE: To characterize the variations in fundus fluorescein angiography (FFA)
      features in idiopathic macular telangiectasia (IMT) type 2. METHODS:
      Retrospective observational study. The authors included all the patients with IMT
      type 2 who underwent FFA during the period from January 2004 to December 2005.
      The main outcome measures were subretinal neovascularization and number and
      distance of telangiectasia from the center of the foveal avascular zone. RESULTS:
      The mean age of 21 patients included in the study was 53.0+/-7.7 years. There
      were 11 women and 10 men. Six of the 21 patients had a history of diabetes
      mellitus. Subretinal neovascularization (SRN) was observed in 10 (23.8%) eyes.
      Subretinal plaque of pigment hyperplasia in the macula was found in 7 (21.9%)
      eyes, and crystalline yellowish deposits on the retinal surface were seen in 19
      (59.4%) eyes. Only one eye had visible retinal telangiectasia. Most had more than
      10 telangiectatic lesions in the macular area and the temporal macula was most
      commonly involved. The mean distance from the center of the foveal avascular zone
      (FAZ) up to which telangiectasia could be observed was 1340+/-400 microm. The
      maximum distance from the FAZ at which telangiectasia was identified was 2530
      microm. CONCLUSIONS: In IMT type 2, telangiectasia may be seen farther from the
      parafoveal area.

PMID- 18609480
TI  - Can intravitreal tissue plasminogen activator and SF6 gas facilitate management
      of macular degeneration with photodynamic therapy?
AB  - PURPOSE: To describe the safety and efficacy of intravitreal tissue plasminogen
      activator (tPA) and sulfur hexafluoride (SF6) gas with sequential photodynamic
      therapy (PDT) in the management of submacular hemorrhage (SMH) associated with
      macular degeneration (MD). METHODS: Consecutive case series of five patients
      presenting with acute SMH from neovascular MD between May 2004 and January 2006
      in a UK Eye Centre. Duration of visual loss was less than 7 weeks. Treatment
      involved intravitreal injections of tPA, SF6 gas to achieve pneumatic
      displacement of SMH, and 24 hours prone posturing. Displacement of SMH was
      assessed by digital photography, and choroidal neovascularization (CNV) was
      reclassified using angiography. PDT was applied when indicated within 1 to 12
      days postoperatively. RESULTS: Adequate displacement of SMH allowed visualization
      of CNV within 24 hours in three of five patients. One patient with large SMH of 7
      weeks duration had partial displacement of SMH. Three patients were reclassified
      with classic CNV after tPA-SF6 injection, and successfully underwent PDT.
      CONCLUSIONS: Intravitreal tPA and SF6 assisted pneumatic displacement of SMH is a
      safe and effective intervention. This technique facilitates more accurate
      angiographic classification of CNV. PDT may be sequentially and rapidly applied
      as early as 1 day after injections. The technique may be offered to patients with
      neovascular MD presenting with acute SMH.

PMID- 18609481
TI  - Assessment of macular function by microperimetry in intermediate age-related
      macular degeneration.
AB  - PURPOSE: To evaluate retrospectively macular function by microperimetry (MP) in
      intermediate age-related macular degeneration (AMD). METHODS: Thirty eyes of 30
      patients with intermediate AMD and a visual acuity of 20/32 or better were
      enrolled in the study. Macular function in patients with intermediate AMD and age
      matched control group were carried out with MP1 microperimeter. Mean sensitivity
      (MS), mean defect (MD) parameters, fixation patterns, and localizations were
      evaluated. Mann-Whitney U test was used for the comparison of macular function
      parameters between the intermediate AMD group and the control group. RESULTS: MS
      was 12.7+/-2.8 dB and MD was detected as -6.2+/-2.2 dB in the intermediate AMD
      group by MP. Fixation patterns were stable in 22 eyes, relatively unstable in 7
      eyes, and unstable in 1 eye. Fixation location was predominantly central in 19
      eyes, poor central in 5 eyes, and predominantly eccentric in 6 eyes. In the
      control group MS was 18.0+/-0.6 dB and MD was -1.9+/-0.6 dB. When compared with
      control group, the decrease in MS and the increase in MD were statistically
      significant in the intermediate AMD group (p=0.001 and p=0.001, respectively).
      CONCLUSIONS: Assessment of retinal sensitivity with MP1 microperimeter is a
      rapid, safe and noninvasive diagnostic method. Early macular function loss in
      intermediate AMD can be precisely detected by MP1 microperimeter before
      significant visual impairment is established and it is also useful for
      demonstrating the shift in the localization and the stability of fixation prior
      to progression of intermediate AMD to advanced and exudative stage.

PMID- 18609482
TI  - Macular function by multifocal electroretinogram in diabetic macular edema after
      intravitreal triamcinolone acetonide injection.
AB  - PURPOSE: The purpose of this study was to assess macular function by multifocal
      electroretinography (mfERG) in eyes with diabetic macular edema (DME) after
      intravitreal triamcinolone acetonide (IVTA) injection. METHODS: Fifteen eyes of
      15 patients with DME scheduled for 4 mg IVTA injection were prospectively
      recruited. The response to treatment was monitored functionally by visual acuity
      (VA) measurement and mfERG and anatomically by foveal thickness measured by
      optical coherence tomography (OCT). The first-order kernel P1 mfERG responses
      from 0 to 7 degrees (central) and 7 to 25 degrees (peripheral) were grouped and
      analyzed. Changes in functional parameters (VAs and the P1 mfERG response
      amplitudes and peak latencies) and morphometric parameters (OCT foveal thickness)
      in eyes with DME 1 and 3 months after IVTA injection were compared with baseline
      values by Student t test. RESULTS: The mean baseline logMAR value for VAs of the
      patients before treatment was 0.49+/-0.26. After treatment, it was 0.27+/-0.23 at
      1 month and 0.26+/-0.18 at 3 months, and differences from pretreatment values
      were significant (for each, p<0.001). There were statistically significant
      decreases in the mean foveal thickness at 1 and 3 months after treatment compared
      with pretreatment values (for each, p<0.001). There were also statistically
      significant increases in the mean P1 response amplitude for both central and
      peripheral groups at all examinations compared with pretreatment (for each,
      p<0.001). The mean P1 peak latencies for both the central and peripheral groups
      were shortened, but not significantly. CONCLUSIONS: As well as the reduction in
      DME and improvement in VA, IVTA injection improves macular function as assessed
      by mfERG in diabetic patients.

PMID- 18609483
TI  - Prognostic prediction ability of postoperative multifocal ERG after vitrectomy
      for diabetic macular edema.
AB  - PURPOSE: Diabetic macular edema (DME) causes visual loss in diabetic patients.
      Multifocal electroretinograms (mfERGs) have been used to assess macular function
      pre- and postvitrectomy for DME. METHODS: A standard three-port pars plana
      vitrectomy with peeling of inner limiting membrane was performed in 25 eyes of 21
      patients (13 male, 8 female) with DME. For each patient, visual acuity
      examination, measure of retinal thickness (using optical coherence tomography),
      and mfERGs were performed before and 1 week, 1 month, 3 months, and 6 months
      after vitrectomy. RESULTS: Mean postoperative visual acuity was significantly
      improved (p<0.05, t test), with mean increase of 0.17 logMAR units; mean retinal
      thickness was significantly (p<0.001) decreased after surgery (from 537 microm to
      298 microm). The increase of normalized amplitude of central ring was not
      significant; the mean P1 wave-amplitude increased from 0.33 to 0.40 mV; mean P1
      wave-implicit time decreased 2.88 ms. We divided the patients into two groups:
      Group 1 (13 eyes), in which the visual recovery was less than 0.20 logMAR, and
      Group 2 (12 eyes), in which the visual recovery was greater than 0.20 logMAR. ERG
      results were statistically significantly different between the groups (p<0.025),
      when we consider the response recorded from the central ring. In Group 2 there is
      a marked reduction in implicit time of both ERGs waves, which was statistically
      significant for N1 wave (p=0.01). The changes of parameters of mfERG observed 6
      months after surgery were consistent with those recorded just 1 week after
      surgery. CONCLUSIONS: Multifocal electroretinogram can be useful to predict
      functional prognosis in patients with diabetes who underwent vitrectomy for
      diabetic macular edema.

PMID- 18609484
TI  - Ultrasound biomicroscopy after vitrectomy in eyes with normal intraocular
      pressure and in eyes with chronic hypotony.
AB  - PURPOSE: To analyze the ultrasound biomicroscopy (UBM) features of eyes with
      chronic hypotony after pars plana vitrectomy (PPV) and compare them with the UBM
      features of eyes with normal intraocular pressure (IOP) after PPV. METHODS: This
      comparative (nonrandomized) interventional study included 64 eyes of 64 patients
      who underwent PPV. Group 1 included 20 eyes with less complex vitreoretinal
      diseases (VRD) that presented with normal IOP after PPV. Group 2 included 44 eyes
      with severe proliferative vitreoretinopathy (PVR) managed with PPV and silicone
      oil tamponade that presented with complete retina reattachment and chronic ocular
      hypotony. UBM was performed to study the anterior segment, ciliary body (CB), and
      peripheral retina. The UBM findings of the two groups were compared. RESULTS: In
      Group 1, 19/20 eyes presented with no CB alterations detected by UBM. In Group 2,
      43/44 eyes presented with CB alterations that included tractional CB detachment
      (n=16); exudative CB detachment (n=11); tractional CB detachment/CB atrophy
      (n=7); CB hypotrophy (n=5); tractional CB detachment/exudative CB detachment
      (n=3); and CB edema (n=1). There was a strong relationship between IOP and CB
      findings revealed by UBM. CONCLUSIONS: Eyes with hypotony following PPV have CB
      abnormalities that can be detected by UBM. These CB alterations were not found in
      eyes with normal IOP after PPV in this series.

PMID- 18609485
TI  - Orbital and ocular manifestations of acute childhood leukemia: clinical and
      statistical analysis of 180 patients.
AB  - PURPOSE: To investigate the association between presence of orbital or ocular
      lesions and type and stage of leukemia and to investigate whether orbital and
      ocular lesions are significant in predicting leukemia prognosis. METHODS: The
      authors evaluated 180 patients with acute childhood leukemia. Lesions associated
      with leukemia may be classified as specific (due to leukemic infiltration of
      various ocular tissues), nonspecific (due to one of the secondary complications),
      or iatrogenic manifestations caused by chemotherapy. Risk-based treatment
      assignment is based on clinical and laboratory features at diagnosis. Children
      with presenting white blood cell count below 50,000 mm3 are considered at
      standard risk for treatment failure, while all others are considered at high risk
      for treatment failure. RESULTS: Specific lesions were noted in 66% of patients
      with acute myeloid leukemia (AML) and 11.5% patients with acute lymphocytic
      leukemia (ALL) (p<0.05), and were more severe in patients with high risk leukemia
      than in patients with standard risk leukemia. Orbital or ocular lesions were
      noted more commonly in patients with AML (66.6%) compared to patients with ALL
      (15.1%). In both the AML and ALL groups, there was a higher frequency of leukemic
      relapses in the bone marrow and/or central nervous system in patients with
      specific lesions (63.1%) compared to patients with nonspecific lesions (42%), and
      in patients without orbital or ocular lesions (29.2%) (p<0.05). CONCLUSIONS: In
      both the AML and ALL groups, the presence of specific orbital or ocular lesions
      was associated with a higher frequency of bone marrow relapses and CNS
      involvement (p<0.05), leading to a lower survival rate.

PMID- 18609486
TI  - Vigabatrin-induced visual dysfunction in Chinese patients with refractory
      epilepsy.
AB  - PURPOSE: Bilateral visual field constriction has been reported following the use
      of the antiepileptic drug (AED) vigabatrin. The incidence of retinal toxicity is
      variable and there are limited data in Asian populations. The authors report the
      results of ophthalmologic examination in Chinese patients taking this drug.
      METHODS: The authors identified two groups of patients with refractory epilepsy:
      one group on vigabatrin and another cohort of patients taking other AEDs. The
      authors recorded the medical history and performed visual acuity testing,
      intraocular pressure measurement, slit lamp biomicroscopy, and conventional
      automated perimetry with Humphrey Visual Field Analyzer II in all patients.
      RESULTS: Eighteen patients--8 men and 10 women--with a mean age of 23.8 years who
      were taking vigabatrin were reviewed. Length of treatment with this drug ranged
      from 13 months to 5 years and the mean daily dosage was 1581 mg. None of the
      patients in either group had a history of coexisting optic nerve diseases or
      other neurotoxic drug use. Twenty of 36 (55.6%) eyes of the vigabatrin users
      showed significant bilateral visual field defects with 80% showing a concentric
      pattern, compared with none in the control group. CONCLUSIONS: The authors
      confirmed a high prevalence of visual field constriction associated with
      vigabatrin in Chinese patients. The use of alternative novel techniques such as
      measurement of the retinal nerve fibre layer thickness and perimetry may detect
      early retinal damage and result in even higher incidences. Visual field
      monitoring is recommended in patients who continue to take this drug.

PMID- 18609487
TI  - A new visual field test in empty sella syndrome: rarebit perimetry.
AB  - PURPOSE: Several visual field defects can be seen in empty sella syndrome (ESS).
      In this study, the authors aimed to evaluate the visual field defects in patients
      with ESS by rarebit perimetry and to compare the results with Humphrey perimetry.
      METHODS: Left eyes of 13 patients with ESS and left eyes of 15 age-matched normal
      subjects were included in the study. Visual field testing was performed by
      Humphrey Visual Field Analyzer II (Fastpack 30-2 strategy) and rarebit perimetry
      (regular test). Statistical analysis was performed by independent-samples t-test,
      Mann-Whitney U test, receiver operating characteristic (ROC) curves, and Pearson
      correlation test. RESULTS: Humphrey perimetry mean deviation was -3.67 dB in
      control group and -6.06 dB in patients with ESS (p=0.12). Mean hit rate
      calculated by rarebit test was 91.8% in control group and 75.9% in cases with ESS
      (p=0.005). Area under ROC curve was 0.756 for Humphrey visual field test and
      0.827 for rarebit hit rate (p=0.59). There was a significant correlation between
      rarebit hit rate and Humphrey visual field test mean deviation (r=0.755,
      p<0.001). CONCLUSIONS: Rarebit perimetry correlates significantly with Humphrey
      perimeter in detecting visual field defects related with ESS and has a higher
      sensitivity and specificity.

PMID- 18609488
TI  - Loxosceles reclusa bite to the eyelid.
AB  - PURPOSE: The authors report a case of Loxosceles reclusa infestation on the
      eyelid. METHODS: The specimen collected by swabbing the lesions with gauze was
      tested by using a venom-specific enzyme-linked immunosorbent assay. Loxosceles
      venom was detected in specimen. The patient was managed with conservative therapy
      that included saline compresses and ocular lubrication. RESULTS: The case
      presented with severe edema and necrosis on the left upper eyelid. On laboratory
      examination, a significant left shift of white blood cell count was detected.
      Although residual scar of the eyelid and punctate epitheliopathy on the inferior
      of cornea was detected, vision was not impaired. CONCLUSIONS: Supportive therapy
      may be reasonable treatment for Loxosceles reclusa infestation on the eyelids.
      The presence of venom proteins detected with an enzyme-linked immunosorbent assay
      technique is beneficial for supporting the diagnosis of Loxosceles envenomatio.

PMID- 18609489
TI  - Ocular manifestations in a case of childhood cicatricial pemphigoid.
AB  - PURPOSE: Cicatricial pemphigoid is a rare chronic autoimmune disease,
      characterized by progressive alterations on the skin and mucous membranes. Ocular
      lesions consists of chronic conjunctivitis, progressive subepithelial fibrosis on
      the conjunctival fornix together with symblepharon formation, obstruction of the
      Meibomian ducts, sicca syndrome, and occasionally, entropion associated with
      consequent trichiasis and corneal ulcers. METHODS: A 9-year-old patient with
      cicatricial pemphigoid with severe eye involvement came to our observation. A
      complete anamnesis, ophthalmologic examination, and systemic evaluation,
      including serum antibody levels evaluation and biopsies of mouth, vulva, parotid,
      and intestine mucosa, were performed. RESULTS: Ocular examination showed
      blepharospasm, conjunctival hyperemia, symblepharon, total cicatricial corneal
      leucoma, severe dryness, trichiasis, and eyelid edema. The results of medical and
      surgical treatment are reported. CONCLUSIONS: Given the serious clinical picture,
      possibly due to a late diagnosis, it was not possible to avoid relapse and
      appearance of new cicatricial adherences for which we considered wait and see the
      most appropriate approach, protecting the anterior segment of both eyes,
      sacrificing their function. Further follow-up was not possible as the patient
      died. An early diagnosis would have had a significant influence on the clinical
      course and on the response to therapy.

PMID- 18609490
TI  - Burn during a routine pterygium excision operation.
AB  - PURPOSE: To report a patient who sustained a spark fire burn during a routine
      pterygium operation. METHODS: A 40-year-old woman was referred for pterygium
      excision in her left eye. During the operation a low temperature cautery caused a
      spark fire that resulted in left eye corneal burn, upper and lower eyelid burns,
      and melting of eyelashes and eyebrows bilaterally. RESULTS: Topical antibiotics
      and vitamin C followed by topical corticosteroids were given. After 1 week the
      corneal epithelium healed but a paracentral corneal opacity developed. Two months
      later on last follow-up visit, a mild diffuse corneal opacity was still seen. The
      combination of three elements found in most routine (ophthalmologic) surgical
      fields-an enriched oxygen environment with the high temperature transmitted by
      the electrocautery in the vicinity of hair-might explain the event. CONCLUSIONS:
      Surgeons should try to separate these three elements or eliminate any of them, in
      order to minimize or prevent such events.

PMID- 18609491
TI  - Automatized large diameter lamellar keratoplasty and stem cell transplantation
      for the treatment of ocular surface diseases with limbal insufficiency.
AB  - PURPOSE: To report a new surgical procedure for the treatment of ocular surface
      diseases associated with severe limbal insufficiency. METHODS: A retrospective
      review of four patients with severe ocular surface disease who required stem cell
      transplantation and keratoplasty for the correction of limbal insufficiencies.
      They underwent large diameter lamellar keratoplasty with microkeratome. When
      limbal dysfunction was associated with limited alteration of the ocular surface
      and transparent deep corneal stroma only the anterior corneal stroma was
      transplanted. When the entire corneal thickness was compromised, both anterior
      and deep donor buttons were transplanted. RESULTS: Patients remained stable and
      improved their visual acuity after surgery. Best-corrected visual acuity ranged
      from 20/200 to 20/30. No corneal graft rejections were found. The main
      complication found in one of our patients was a central stromal opacity which
      required a secondary penetrating keratoplasty. CONCLUSIONS: Automatized large
      diameter lamellar keratoplasty provides a safe and successful alternative to
      limbal transplantation for limbal insufficiency associated with corneal opacity.
      This technique enables a single-stage surgical procedure and the use of a single
      donor which reduces the risk of rejection. In addition, better refractive results
      are achieved due to the quality of the interface and the absence of corneal
      sutures.

PMID- 18609492
TI  - Short-term anatomic effect of ranibizumab for polypoidal choroidal vasculopathy.
AB  - PURPOSE: To assess the short-term anatomic effect of intravitreal ranibizumab for
      polypoidal choroidal vasculopathy. METHODS: All patients had undergone a full
      ophthalmic examination. A monthly injection of ranibizumab was performed for 3
      months. Indocyanine angiography (ICG) and optical coherence tomography (OCT) were
      performed 1 month after the third-month ranibizumab injection. RESULTS: Polyps
      disappeared on ICG angiography in 9 out of 13 lesions (69.2%). Retinal thickness
      diminished significantly on OCT (p=0.02). In our series we noticed a significant
      reduction of the percentage of patients presenting with subretinal fluid (p=0.02)
      and pigment epithelium detachment between the initial and final visits (0.016).
      In addition, we noticed that BCVA increased significantly (p 0.02). CONCLUSIONS:
      Monthly intravitreal injection of ranibizumab for 3 months has a short-term
      beneficial anatomic effect.

PMID- 18609493
TI  - Bilateral multifocal retinal pigment epithelium detachments associated with
      systemic corticosteroids.
AB  - PURPOSE: To report an unusual case of central serous chorioretinopathy (CSC),
      presenting as bilateral and multifocal isolated serous retinal pigment epithelium
      detachments (RPEDs) following corticosteroid treatment. METHODS: An otherwise
      healthy 39-year-old man was evaluated for visual loss following blunt trauma of
      his right eye (RE). The patient underwent complete bilateral ophthalmologic
      examination, including optical coherence tomography and fluorescein (FA) and
      indocyanine green angiography (ICGA). RESULTS: At presentation, best-corrected
      visual acuity (BCVA) was 20/200 in the RE and 200/200 in the left eye (LE).
      Treatment included topical and oral corticosteroids. Three days later, the
      patient complained of metamorphopsia and further decrease in the VA of his RE.
      Fundus examination showed bilateral serous RPEDs. Optical coherence tomography,
      FA, and ICGA confirmed the diagnosis. Topical and oral corticosteroids were
      stopped and a follow-up examination 5 days later demonstrated marked resolution
      of the RPEDs in the RE. Five weeks later, RPEDs regressed in the RE while they
      persisted in the asymptomatic LE. Visual acuity in the RE further improved to
      120/200. Nine months after the first visit, BCVA in the RE was 200/200. At that
      time, both eyes demonstrated retinal pigment epitheliopathy. CONCLUSIONS: Central
      serous chorioretinopathy is a known complication of corticosteroids. The classic
      variant of CSC consists of a shallow neuroretinal detachment located at the
      posterior pole of the fundus. Bilateral and multifocal isolated serous RPEDs
      represent an atypical form of CSC.

PMID- 18609494
TI  - Acute visual loss and chorioretinal infarction after photodynamic therapy
      combined with intravitreal triamcinolone.
AB  - PURPOSE: To report acute visual loss associated with dynamic vascular changes
      after photodynamic therapy (PDT) combined with intravitreal triamcinolone (IVTA)
      for the treatment of occult choroidal neovascularization (CNV). METHODS: An 86
      year-old woman complained of visual loss in her left eye. Angiographic
      examination showed a serous pigment epithelium detachment complicated by CNV. She
      underwent combined treatment with IVTA (4 mg) followed by standard verteporfin
      PDT administered after a 5-day interval. RESULTS: The patient developed vision
      loss 1 day after PDT. Ophthalmoscopic examination disclosed an acute serous
      neurosensory retinal detachment. Fluorescein angiography showed a large area of
      early hypofluorescence in correspondence to and extending beyond the photodynamic
      spot. Neurosensory retinal vessels involvement with dilation of the retinal
      arterioles and capillary nonperfusion were also revealed. Indocyanine green
      angiography showed choroidal infarction within the collateral choroid included in
      the area of light exposure, with associated nonperfusion of medium and large
      choroidal vessels being revealed. Five days after PDT, spontaneous severe
      bleeding with breakthrough into the vitreous occurred, in addition to an RPE
      tear. CONCLUSIONS: Acute loss of vision associated with vascular changes in
      retinal and choroidal circulation represents an uncommon but serious complication
      following combined PDT and IVTA. These risks should be carefully considered in
      combination therapies.

PMID- 18609495
TI  - Bilateral macular detachment caused by bilateral optic nerve malformation in a
      papillorenal syndrome due to a new PAX2 mutation.
AB  - PURPOSE: Papillorenal syndrome is an autosomal dominant entity due to PAX2 gene
      mutation, involving optic nerve and renal malformations. METHODS: The authors
      report a 19-year-old man with bilateral macular detachment associated with optic
      nerve pit in one eye and morning glory syndrome in the other eye. The patient
      underwent three-port pars plana vitrectomy, endolaser photocoagulation, and C3F8
      gas tamponade in his best eye. A medical history of vesicoureteric reflux and
      kidney hypoplasia led to genetic analysis. RESULTS: Molecular genetic PAX2
      analysis revealed a novel nondescribed mutation in exon 3. One year
      postoperatively, ophthalmologic outcomes were satisfactory with complete
      flattening of the retina and improvement of the best-corrected visual acuity to
      11/10. CONCLUSIONS: PAX2 is involved in the optic vesicles, genital tracts,
      kidney, and central nervous system embryogenic development. The association of
      optic nerve and renal malformations should lead to the suspicion of papillorenal
      syndrome with PAX2 mutation.

PMID- 18609496
TI  - Vitreous prolapse through the scleral wound in 25-gauge transconjunctival
      vitrectomy.
AB  - PURPOSE: To examine the effectiveness of excising peripheral vitreous until the
      cannula tip is exposed to prevent vitreous prolapse through the scleral wound in
      25-gauge transconjunctival vitrectomy. METHODS: Twenty-five-gauge vitrectomy was
      performed in 60 consecutive eyes. Peripheral vitrectomy was conducted until the
      cannula tip was exposed in 30 eyes and with conservation of the vitreous around
      the cannula in 30 eyes. Vitreous prolapse through the scleral wound was examined
      using a suction stick. RESULTS: Vitreous prolapse through the scleral wound was
      transparent, fine and short, and detectable only with the suction stick. The
      incidence of vitreous prolapse through the scleral wound was 0% (0 of 30 eyes)
      when peripheral vitreous was excised until the cannula tip was exposed, and 20%
      (6 of 30 eyes) when the vitreous around the cannula was conserved, with a
      significant difference between two groups (p=0.0237). In two of six eyes with
      vitreous prolapse, the scleral wound was open, but there was no leakage of
      intraocular fluid and normal ocular pressure was maintained. CONCLUSIONS: If
      peripheral vitrectomy is performed without excising the vitreous surrounding the
      cannula, there is a 20% risk of the vitreous prolapsing through the scleral
      wound. Vitreous prolapse through the scleral wound is difficult to detect because
      it is transparent, fine and short, and there is no intraocular fluid leakage.
      Therefore, detecting vitreous prolapse with a suction stick and appropriate
      intervention are important for preventing endophthalmitis.

PMID- 18609497
TI  - Comment on papper: Cyclooxygenase-2 expression in primary and recurrent
      pterygium.

PMID- 18609499
TI  - Human adipose-derived stem cells as future tools in tissue regeneration:
      osteogenic differentiation and cell-scaffold interaction.
AB  - Tissue engineering is now contributing to new developments in several clinical
      fields, and mesenchymal stem cells derived from adipose tissue (hASCs) may
      provide a novel opportunity to replace, repair and promote the regeneration of
      diseased or damaged musculoskeletal tissue. Our interest was to characterize and
      differentiate hASCs isolated from twenty-three donors. Proliferation, CFU-F,
      cytofluorimetric and histochemistry analyses were performed. HASCs differentiate
      into osteogenic, chondrogenic, and adipogenic lineages, as assessed by tissue
      specific markers such as alkaline phosphatase, osteopontin expression and
      deposition of calcium matrix, lipid-vacuoles formation and Glycosaminoglycans
      production. We also compared osteo-differentiated hASCs cultured on monolayer and
      loaded on biomaterials routinely used in the clinic, such as hydroxyapatite,
      cancellous human bone fragments, deproteinized bovine bone granules, and
      titanium. Scaffolds loaded with pre-differentiated hASCs do not affect cell
      proliferation and no cellular toxicity was observed. HASCs tightly adhere to
      scaffolds and differentiated-hASCs on human bone fragments and bovine bone
      granules produced, respectively, 3.4- and 2.1-fold more calcified matrix than
      osteo-differentiated hASCs on monolayer. Moreover, both human and deproteinized
      bovine bone is able to induce osteogenic differentiation of CTRL-hASCs. Although
      our in vitro results need to be confirmed in in vivo bone regeneration models,
      our data suggest that hASCs may be considered suitable biological tools for the
      screening of innovative scaffolds that would be useful in tissue engineering.

PMID- 18609501
TI  - Chondrocyte response to high regimens of cyclic hydrostatic pressure in 3
      dimensional engineered constructs.
AB  - PURPOSE: Despite widespread use of 3-dimensional (3D) micro-porous scaffolds to
      promote their potential application in cartilage tissue engineering, only a few
      studies have examined the response to hydrostatic pressure of engineered
      constructs. A high cyclic pressurization, currently believed to be the
      predominant mechanical signal perceived by cells in articular cartilage, was used
      here to stimulate bovine articular chondrocytes cultured in a synthetic 3D porous
      scaffold (DegraPol). METHODS: Construct cultivation lasted 3 days with applied
      pressurization cycles of amplitude 10 MPa, frequency 0.33 Hz, and stimulation
      sessions of 4 hours/day. RESULTS: At 3 days of culture, with respect to pre
      culture conditions, the viability of the pressurized constructs did not vary,
      whereas it underwent a 16% drop in the unpressurized controls. Synthesis of alfa
      actin was 34% lower in all cultured constructs. Synthesis of collagen II/collagen
      I did not vary in pressurized constructs, was 76% lower in unpressurized
      controls, and was around 230% higher in pressurized constructs with respect to
      unpressurized controls. Chondrocytes showed a phenotypic spherical morphology at
      time zero and at 3 days of pressurized culture. CONCLUSIONS: Although the passage
      from 2D expansion to 3D geometry was effective to guide cell differentiation,
      only mechanical conditioning enabled the maintenance and further cell
      differentiation toward a mature chondrocytic phenotype.

PMID- 18609500
TI  - Mesenchymal stem cell-based repair of articular cartilage with polyglycolic acid
      hydroxyapatite biphasic scaffold.
AB  - This study investigates the capacity of a composite scaffold composed of
      polyglycolic acid-hydroxyapatite (PGA-HA) and autologous mesenchymal stem cells
      (MSCs) to promote repair of osteochondral defects. MSCs from culture-expanded
      rabbits were seeded onto a PGA and HA scaffold. After a 72-hour co-culture
      period, the cell-adhered PGA and HA were joined together, forming an MSCs-PGA-HA
      composite. Full-thickness cartilage defects in the intercondylar fossa of the
      femur were then implanted with the MSC-PGA-HA composite, the PGA-HA scaffold
      only, or they were left empty (n=20). Animals were sacrificed 16 or 32 weeks
      after surgery and the gross appearance of the defects was evaluated. The
      specimens were examined histologically for morphologic features, and stained
      immunohistochemically for type 2 collagen. Specimens of the MSCs-PGA-HA composite
      implantation group demonstrated hyaline cartilage and a complete subchondral bone
      formation. At 16 weeks post-implantation, significant integration of the newly
      formed tissue with surrounding normal cartilage and subchondral bone was observed
      when compared to the two control groups. At 32 weeks, no sign of progressive
      degeneration of the newly formed tissue was found. A significant difference in
      histological grading score was found compared with the control groups. The novel
      MSCs-seeded, PGA-HA biphasic graft facilitated both articular cartilage and
      subchondral bone regeneration in an animal model and might serve as a new
      approach for clinical applications.

PMID- 18609502
TI  - Functional hepatocyte-like cells derived from human bone marrow mesenchymal stem
      cells on a novel 3-dimensional biocompatible nanofibrous scaffold.
AB  - AIM: To supporting growth and functional differentiation of adult stem cells into
      hepatocytes in a well-controlled manner, we performed differentiation of human
      bone marrow mesenchymal stem cells (hBMSCs) to hepatocytes-like cells on a
      constructed 3-dimensional (3D) nanofibrous biocompatible scaffold. METHODS: After
      characterization of the hBMSCs isolated from human bone marrow, the performance
      of the cells seeded and their proliferation on the scaffold was evaluated by
      scanning electron microscopy (SEM) and 3-(4,5-dimethylthiazole-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Different approaches such as
      immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR),
      and biochemical assays were used to estimate the ability of hBMSC-derived cells
      to express hepatocyte-specific markers. RESULTS: Scanning electron micrographs
      and MTT analysis revealed the cells were able to expand and remained biologically
      and metabolically active for 21 days. Immunocytochemical analysis of albumin and
      alfa-fetoprotein showing the accumulation of these markers in differentiated
      cells was confirmed by RT-PCR. Additional markers such as cytochrome P450 3A4,
      cytokeratin-18, and cytokeratin-19 detected by RT-PCR showed progressive
      expression during 3 weeks of differentiation on 3D scaffold. The hepatocyte-like
      cells displayed several characteristics of metabolic functions as judged by
      production of albumin, urea, transferrin, serum glutamic pyruvic transaminase
      (SGPT), and serum oxaloacetate aminotransferase (SGOT). Levels of above-mentioned
      markers, except SGOT in differentiated cells on scaffold, were found to be
      significantly greater than in the 2D culture system (p<0.05). CONCLUSION: Overall
      data suggest that the engineered nanofibrous scaffold is a conductive matrix for
      functional hBMSC-derived hepatocyte-like cells and is promising for maintenance
      of hepatocytes suitable for implantation.

PMID- 18609503
TI  - Concept and computational design for a bioartificial nephron-on-a-chip.
AB  - A MEMS-based, (Micro Electro Mechanical System) bioartificial device is proposed
      for replicating the function of a single nephron. Consistent with the anatomy and
      physiology of humans, our device has 3 distinct sections, replicating the
      function of the glomerulus, the proximal tubule, and the loop of Henle.
      Construction of a bioartificial loop of Henle in particular requires control of
      diffusion-scale features. The proposed device can be built using existing
      microfabrication technologies and populated with various renal cell types. A
      computational model is also developed to analyze the coupled, multiphase mass
      transport in this system. Using the model, a design is generated with flow and
      solute transport properties matching those of the human nephron.

PMID- 18609504
TI  - The role of extracorporeal blood purification therapies in the prevention of
      radiocontrast-induced nephropathy.
AB  - Radiocontrast-induced nephropathy (RCIN) is a common and potentially serious
      complication following diagnostic and therapeutic cardiology procedures using
      radiocontrast media. The first and most important step in reducing the likelihood
      of RCIN is to identify patients at risk, by medical history and measurement of
      serum creatinine concentration to allow calculation of estimated glomerular
      filtration rate (GFR). Extracorporeal blood purification effectively removes
      radiocontrast media from the circulation. Periprocedural extracorporeal blood
      purification (hemodialysis or continuous renal replacement therapy) does not
      reduce the incidence of RCIN compared with standard medical therapy, and cannot
      be recommended at this time. The potential benefit of continuous venovenous
      hemofiltration published by a single center should be confirmed with further
      studies before it can be recommended or disregarded, and higher doses of
      continuous renal replacement therapy may also merit further investigation.

PMID- 18609505
TI  - Operational characteristics of continuous renal replacement modalities used for
      critically ill patients with acute kidney injury.
AB  - Renal replacement therapy (RRT) is required in a significant percentage of
      patients developing acute kidney injury (AKI) in an intensive care unit (ICU)
      setting. One of the foremost objectives of continuous renal replacement therapy
      (CRRT) is the removal of excess fluid and blood solutes that are retained as a
      consequence of decreased or absent glomerular filtration. Because prescription of
      CRRT requires goals to be set with regard to the rate and extent of both solute
      and fluid removal, a thorough understanding of the mechanisms by which solute and
      fluid removal occurs during CRRT is necessary. The following provides an overview
      of solute and water transfer during CRRT and this information is placed in the
      appropriate clinical context with a discussion of recent clinical trials
      assessing the relationship between CRRT dose and patient survival. Moreover, the
      differences between solute removal in CRRT and other dialysis modalities,
      especially sustained low-efficiency dialysis (SLED) and extended daily dialysis
      (EDD), along with the potential clinical implications are discussed.

PMID- 18609506
TI  - Vascular endothelial growth factor in dialysate in relation to intensity of
      peritoneal inflammation.
AB  - BACKGROUND: Peritoneal inflammation may induce changes in peritoneal
      microvessels, including neoangiogenesis/vasculogenesis, leading to increased
      peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We
      hypothesized that an inflammatory reaction in the peritoneal cavity during
      peritonitis induces increased synthesis of vascular endothelial growth factor
      (VEGF). We therefore studied the relationship between peritoneal inflammation
      markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal
      inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based
      dialysis solution. METHODS: Under ether anesthesia, male Wistar rats were
      injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or
      with LPS (microg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1;
      n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal
      solute transport rate (PSTR) and dialysate cell count (DCC) were measured and
      effluent samples were collected. RESULTS: LPS i.p. resulted in increased PSTR and
      decreased IPV (p<0.005). DCC (cells/microL) and the neutrophil/macrophage ratio
      were higher for all LPS concentrations compared to the control group. After 8
      hours, LPS-exposed rats had significantly higher dialysate levels of all
      investigated cytokines (TNF-alfa, MCP-1 and IL-10) than the control group.
      Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS
      0.001, 28.2+/-5.9; LPS 0.01, 38.9+/-11.6; LPS 0.1, 43.0+/-5.9; LPS 1.0, 46.6+/
      11.3; Control, 14.5+/-9.8; p<0.0005 for all LPS vs. Control). CONCLUSIONS: The
      infusion of Dianeal 3.86% with different doses of LPS induced a strong acute
      intraperitoneal inflammatory reaction with increased DCC and cytokine levels,
      resulting in increased peritoneal solute transport and decreased IPV. LPS induced
      a dose-dependent parallel increase of the intraperitoneal concentrations of MCP
      1, IL-10 and TNF-alfa, as well as of VEGF. These results suggest that
      intraperitoneal VEGF synthesis is induced in response to inflammation, and that
      this may be an important component in the process leading to peritoneal transport
      alterations.

PMID- 18609507
TI  - Effect of vitamin E-coated dialysis membranes on anemia in patients with chronic
      kidney disease: an Italian multicenter study.
AB  - BACKGROUND: Increased oxidant stress is increasingly recognized as a crucial
      factor in anemia in patients with chronic kidney disease. Vitamin E-coated
      membranes (VECMs) consist of a multilayer membrane with liposoluble vitamin E on
      the blood surface allowing direct free radical scavenging at the membrane site,
      which is of potential clinical benefit. Our objective was to examine the effect
      of VECMs on anemia in chronic hemodialysis (HD). METHODS: We enrolled 172 stable
      chronic HD patients (94 men, 78 women, age 65.4 +/- 13.4 years) in an open-label
      multicenter study. They were shifted from their previous dialyzer to VECM for 1
      year. Hemoglobin (Hb) levels and recombinant human erythropoietin (rHuEpo) dosage
      were analyzed after 4, 8, and 12 months on the VECM and compared with baseline
      values using paired tests. RESULTS: Hb significantly increased from 10.9 +/- 1.2
      g/dL at baseline to 11.7 +/- 1.2 g/dL after 12 months (p<0.001) on VECMs.
      Conversely, the rHuEpo dosage decreased from 7,762 +/- 5,865 IU/week at baseline
      to 6,390 +/- 5,679 IU/week after 12 months (p<0.001). The proportion of patients
      who were at target Hb levels (European Best Practice Guidelines) increased from
      49.4% at baseline to 80% after 12 months (p<0.001). CONCLUSIONS: Dialysis with
      VECM in stable chronic HD patients was associated with significantly improved Hb
      levels and lower rHuEpo requirements. These results suggest that the antioxidant
      properties of VECMs may impact favorably on anemia management in chronic HD
      patients. Possible mechanisms include enhanced membrane biocompatibility, reduced
      oxidative stress and inflammation with VECMs, resulting in improved red blood
      cell survival and/or rHuEpo responsiveness. This therapy may potentially
      contribute to more effective anemia management in hemodialysis patients, and
      merits further rigorous study.

PMID- 18609508
TI  - Three-dimensional dialysate flow analysis in a hollow-fiber dialyzer by perfusion
      computed tomography.
AB  - Perfusion computed tomography (PCT) is a means to rapidly and easily evaluate
      cerebral perfusion in patients presenting with acute stroke symptoms, which
      provides insights into capillary-level hemodynamics. In this study, we used PCT
      to analyze the 3-dimensional dialysate flow in a low-flux hemodialyzer equipped
      with a standard fiber bundle. The dynamic CT studies were performed with 64
      channel multi-detector row CT (MDCT) at a dialysate flow rate of 500 ml/min and a
      1.0 ml/sec injection rate of contrast agent. Central volume principle was used to
      calculate hydrodynamic parameters by deconvolution of time-density curves (TDCs).
      Functional maps of dialysate flow (DF), dialysate volume (DV), and mean transit
      time (MTT) could quantitatively describe the dialysate flow maldistribution,
      variations in fiber packing, and perfusion pressure distribution in a
      hemodialyzer, respectively. PCT by means of analysis was able to overcome the
      limitations of conventional imaging techniques for analyzing dialysate flow
      distributions in hollow-fiber dialyzers. Not only local hydrodynamic phenomena at
      microscopic level but also macroscopic flow behavior of dialysate were visualized
      quantitatively. Therefore, we concluded that PCT is a quantitative analysis
      method to provide better insights into hydrodynamics of hollow-fiber dialyzers
      and is expected to contribute to optimization of artificial kidneys.

PMID- 18609509
TI  - Fenoldopam in cardiac surgery-associated acute kidney injury.

PMID- 18609510
TI  - Vascular access: past, present, and future.
AB  - Vascular access is the Achilles' heel of hemodialysis. Current vascular access
      approaches for hemodialysis include arteriovenous (AV) fistula, AV graft, and
      central venous catheter. Strengths and weaknesses of each access type are
      described. New technology and procedures in introducing an access, monitoring
      access function, and salvaging a non-functioning access are also described.

PMID- 18609511
TI  - Hepatitis B virus infection in the dialysis population: current perspectives.
AB  - One of the major advances in the management of patients on regular dialysis has
      been the control of the spread of hepatitis B virus (HBV) infection in dialysis
      units. The rate of HBsAg positive patients on regular dialysis in the developed
      world is currently low, but outbreaks of HBV continue to occur. The diffusion of
      HBV in dialysis units in developing countries is higher, although available
      information is not abundant. There are limited data on the natural history of HBV
      in the dialysis population; they support a detrimental effect of HBV on survival
      in dialysis patients. The HBV viral load in HbsAg-positive dialysis patients
      appears low and stable over time and numerous mechanisms have been posited to
      explain it. Several assays for detecting HBV DNA in serum are available but they
      should not be used for purposes of routine screening within dialysis units. The
      epidemiology and clinical significance of occult HBV infection in the dialysis
      population needs to be addressed adequately - this remains an area of active
      research. Recent recommendations for the management of HBsAg chronic carriers on
      maintenance dialysis have been issued. No controlled trials for the treatment of
      hepatitis B with either interferon or lamivudine in dialysis patients are
      currently available.

PMID- 18609512
TI  - Residual of bacterial DNA in hemodialyzers: the proof of subclinical infection
      sustaining chronic inflammation.
AB  - BACKGROUND AND PURPOSE: Inflammation and infection seem to be important causes of
      morbidity and mortality in Chronic Kidney Disease (CKD) patients. Subclinical
      infections have been proposed as an important cause of inflammatory syndrome but
      to date this hypothesis remains speculative. In this investigation, we developed
      a method for molecular detection of the presence of bacterial DNA in a population
      of chronic kidney disease patients in order to correlate molecular data with the
      degree and level of inflammation and to evaluate the usefulness of the method in
      the diagnosis of subclinical infection. DESIGN: The study was divided into two
      phases: the study of a population of 81 CKD patients for prevalence and level of
      inflammation and infection; and the molecular evaluation of a subgroup of 38
      patients without evident clinical causes of inflammation for molecular evaluation
      of subclinical infection. RESULTS: Patients hemoculture negative turned out
      positive for the presence of bacterial DNA when molecular methods were used. We
      found a trend of correlation with the presence of bacterial DNA and the increase
      in hs-CRP, IL-6 and oxidative stress (AOPP) levels and a reduction in MFI DR+.
      Hemodialyzer membranes seem to have properties that are 'sticky' to
      bacteria/bacterial DNA and work as concentrators. Moreover our data suggest that
      DNA can traverse hemodialysis membranes. CONCLUSIONS: Molecular methods have
      turned out to be far more sensitive than standard methods in detecting
      subclinical infection. The presence of bacterial DNA seems to influence the
      variation of some parameters of inflammation and immunity. Apart from the
      limitations and pitfalls, a molecular method could be useful for the screening of
      subclinical infection and diagnosis of sepsis when the hemoculture is negative.
      The identification of the microorganism involved, however, must be done with
      species-specific primers. These results are preliminary and more investigations
      will have to be performed in order to confirm our results.

PMID- 18609513
TI  - High serum levels of soluble Fas (sFas) in CKD patients: effects of renal
      clearance, reabsorption and synthesis.
AB  - PURPOSE: Increased serum concentrations of soluble Fas (sFas) have been reported
      in patients with chronic kidney disease (CKD). However, little is known about the
      renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the
      behavior of sFas synthesis in CKD. MATERIALS AND METHODS: We studied 69 patients
      with CKD (60+/-15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14
      healthy subjects (61+/-17 years, creatinine clearance 79+/-24 ml/min/1.73 m2).
      ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein
      (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes. RESULTS: Serum
      sFas levels were significantly higher in patients with CKD (2781+/-1214 vs.
      2196+/-773, p=0.02). The concentrations of sFas in 24-hour urine samples (23+/-27
      vs. 40+/-17, p=0.006) and sFas Clearance (0.019+/-0.022 vs. 0.036+/-0.020,
      p=0.01) were significantly lower in patients with CKD. sFas clearance correlated
      with creatinine clearance (r=0.25, p=0.02). Urine concentrations of RBP
      correlated with sFas concentrations in the urine (r=0.80, p<0.001). sFasmRNA were
      higher in patients with CKD (3.9+/-1.8 vs. 2.5+/-0.9, p<0.001). CONCLUSIONS: In
      CKD patients, the decrease in renal function is followed by a decrease in sFas
      clearance and an increase in serum sFas. In patients with proximal tubule
      dysfunction (high urinary RBP concentrations), urinary sFas is also increased,
      suggesting that sFas is reabsorbed by the proximal tubule. It is possible that an
      increase in sFas synthesis also contributes to the increase of serum sFas
      concentrations in uremia.

PMID- 18609514
TI  - The importance of dialysate sodium concentration in determining interdialytic
      weight gains in chronic hemodialysis patients: the PanThames Renal Audit.
AB  - BACKGROUND AND OBJECTIVES: There is controversy as to the optimum dialysate
      sodium to be used for hemodialysis patients, with reports of hypertension and
      increased interdialytic weight gains with high sodium dialysates and
      intradialytic hypotension and cramps with low sodium dialysates. METHODS: We
      analyzed the effect of different dialysate sodium concentrations during a one
      week period in an audit of 2187 established patients regularly receiving dialysis
      three times a week. Patients were given general dietary advice to restrict
      dietary sodium intake, but no systematic assessment of dietary sodium intake was
      undertaken. RESULTS: The prescription of a dialysate sodium concentration of 140
      mmol/L and >140 mmol/L, was associated with greater interdialytic weight gains,
      3.5% and 4.1% respectively, compared to 2.8% and 2.7% for those using dialysate
      sodium concentrations of 137 and 136 mmol/L, respectively (p0<.05). The mean
      pulse pressure was greater patients dialyzing using a sodium of 140 mmol/L,
      compared to 136 mmol/L, 70 (13) vs 63 (15) mmHg (p<0.011). In addition, 13.5% of
      patients using the highest sodium dialysate suffered symptomatic intradialytic
      hypotension requiring intravenous fluid resuscitation, compared to 2.7% who used
      the lowest sodium concentrate (p<0.05). CONCLUSIONS: This analysis would support
      the use of lower dialysate sodium concentrations to aid in reducing interdialytic
      weight gains and subsequent intradialytic hypotension.

PMID- 18609515
TI  - Regional citrate anticoagulation for hemodialysis: calcium-free vs. calcium
      containing dialysate - a randomized trial.
AB  - BACKGROUND: The majority of citrate protocols for hemodialysis (HD) use calcium
      (Ca)-free dialysate, a limited number use dialysate with Ca, aiming to simplify
      the procedure. This randomized clinical study sought to compare the anticoagulant
      effect of citrate using Ca-free dialysate and dialysate with Ca 1.25 mmol/L.
      METHODS: Fifty HD procedures (in 5 chronic HD patients treated by chronic citrate
      anticoagulation) were randomly assigned to Ca-free dialysate (25 procedures) or
      Ca-1.25 dialysate (25 procedures), both with Mg 0.5 mmol/L, Na 138 mmol/L, and
      bicarbonate 28 mmol/L. Ca-free HD: 15% Na3 citrate 80 ml/hour was infused into
      the arterial line, and 1 M CaCl2, 14 ml/hour into the venous line. Ca-1.25 group:
      15% Na3 citrate 100 ml/hour, 1 M CaCl2 2-4 ml/hour. Polyflux H dialyzers were
      used. Antithrombotic effect was assessed visually after HD at 3 points: dialyzer,
      arterial, and venous bubble traps, using a score of 5 (no clotting) to 1 (total
      clotting). RESULTS: Ca-free group: arterial bubble trap score 4.7 +/- 0.5,
      dialyzer 4.5 +/- 0.6, venous bubble trap 4.8 +/- 0.6. Ionized calcium (iCa) at
      dialyzer inlet 0.34 +/- 0.17, outlet 0.21 +/- 0.06 mmol/L. All HDs were completed
      successfully. Ca-1.25 group: arterial bubble trap score 4.7 +/- 0.5 (NS),
      dialyzer 2.6 +/- 1.04 (p<0.01), venous bubble trap 2.4 +/- 0.9 (p<0.01). Volume
      of clot in venous bubble trap was 1.9 +/- 1.8 mL (range 0.5-6 mL). iCa at
      dialyzer inlet 0.24 +/- 0.05 mmol/L (p<0.05), outlet 0.63 +/- 0.11 mmol/L
      (p<0.01). Four of 25 HD procedures (16%) were prematurely terminated due to
      threatening dialyzer clotting, in 6/25 HD procedures (24%), the venous line was
      changed (p<0.01). CONCLUSION: Citrate anticoagulation with Ca-1.25 dialysate
      resulted in significantly worse anticoagulation of dialyzer and venous bubble
      trap compared with Ca-free dialysate, despite higher citrate dose.

PMID- 18609516
TI  - Selective albumin exchange: a novel and simple method to remove bilirubin.
AB  - PURPOSE: Owing to its non-selectivity, plasma exchange has limited use in the
      treatment of patients with hepatic failure, although it is effective in removal
      of protein-bound toxins. This study reports a novel way to perform selective
      albumin exchange (SAE) by using a secondary plasma separator and aims to study
      its depurative capacity in the removal of bilirubin. METHOD: In ex vivo
      experiments, the sieving coefficients (SCs) of plasma proteins for two secondary
      plasma separators, EC20W and EC30W (Asahi Medical, Tokyo, Japan), were measured.
      The EC20W membrane was chosen for use in clinical treatment because of its higher
      selectivity in separating albumin from plasma than the EC30W. The SCs of albumin,
      immunoglobumin G, A and M (IgG, IgA, IgM) for the EC20W were 0.3+/-0.021, 0.017+/
      0.012, and 0, respectively. Five inpatients with plasma total bilirubin (TB) more
      than 200 micromol/L were enrolled in the present study and received a total of 10
      SAE therapy sessions. Each session lasted 10 hours. SAE using the EC20W was
      conducted, making it similar to post-dilution continuous veno-venous
      hemofiltration (CVVH), with a filtrate rate of 2000 ml/h. Replacement fluid was
      composed by adding human albumin into conventional CVVH replacement fluid, with a
      final albumin concentration of 0.6%. During each treatment, the parameters of
      plasma and filtrate TB, direct bilirubin (DB), indirect bilirubin (IDB), and
      proteins were dynamically monitored. Hemostasis parameters were measured before
      and after sessions. RESULTS: The reduction ratio of plasma TB, DB, and IDB after
      a single session was 29.1+/-3.0%, 31.3+/-4.5%, and 18.7+/-10.2%, respectively.
      The clearance of TB at initiation was 11.1+/-1.3 mL/min and declined to 4.4+/-0.5
      ml/min at the end (p<0.01). This decline was accompanied by a reduction in
      albumin SC from 0.3+/-0.021 to 0.13+/-0.05. The molar ratio of bilirubin to
      albumin in filtrate was comparable to that in plasma. After a single treatment,
      plasma protein concentration including total protein, albumin, IgA and IgM
      remained unaffected, except for globulin and IgG, which were reduced by 11.5+/
      7.8% and 11.1+/-2.3%, respectively. An improvement in hemostasis parameters,
      including plasma fibrinogen, prothrombase time and INR, was found after
      treatment. No obvious side effects were reported during any of the sessions.
      CONCLUSION: Selective albumin exchange is a simple and effective method to remove
      bilirubin. However, further studies are required to verify its effects on
      clinical outcome.

PMID- 18609517
TI  - Angiogenesis without functional outcome after mononuclear stem cell transplant in
      a doxorubicin-induced dilated myocardiopathy murine model.
AB  - OBJECTIVES: Cell transplantation is considered a novel approach in the treatment
      of myocardiopathy. The objective of this study was to evaluate the effects of
      autologous mononuclear stem cell therapy in doxorubicin-induced dilated
      myocardiopathy by conducting both functional and histopathologic analysis.
      METHODS: Seventy male rats were doxorubicin injected intraperitoneally for 2
      weeks. At 1 month, the animals that had demonstrated left ventricular ejection
      fractions less than 40% were randomly divided into a mononuclear stem cell group
      and controls. Mononuclear stem cells were isolated. All animals underwent
      echocardiographic study: baseline, pre-cell therapy, and at 1 month post-cell
      therapy, and analyzed by the nonparametric Mann-Whitney test. Transplants were
      performed by subepicardial injections. Standard staining was performed. RESULTS:
      Twenty-three animals were randomly treated: mononuclear stem cell and control
      groups, with 11 rats completing the study. Cell viability was 85%. Mononuclear
      stem cells (n=5; 5x106 cells /300 microL medium) and control (n=6; 300 microL
      medium) were used. The resulting left ventricular ejection fraction in the cell
      therapy group was not significantly different compared with controls (p=0.54).
      New vessels were demonstrated in the subepicardial region. CONCLUSIONS:
      Autologous mononuclear stem cell therapy was not functionally effective in
      doxorubicin-induced dilated myocardiopathy in the animal model under study with
      the experimental conditions, despite occurrence of angiogenic activity.

PMID- 18609518
TI  - Effect of dynamic compression on in vitro chondrocyte metabolism.
AB  - BACKGROUND: Chondrocytes can detect and respond to the mechanical environment by
      altering their metabolism. This study was designed to explore the effects of
      dynamic compression on chondrocyte metabolism. METHODS: Chondrocytes were
      harvested from newborn Wistar rats. After 7 days of expansion, chondrocytes
      embedded in agarose discs underwent uniaxial unconfined dynamic compression loads
      at different amplitudes (5%, 10%, and 15%) and frequencies (0.5 Hz, 1.0 Hz, 2.0
      Hz, and 3.0 Hz) with a duration of 24 hours. The delayed effects on the
      chondrocytes were studied at 1, 3, and 7 days after the experiment. RESULTS: The
      results showed that at 10% strain, higher-frequency compression pressure can
      enhance the proliferation of chondrocytes. The synthesis of glycosaminoglycan
      (GAG) increased at 10%-15% strain and a 1-Hz load. The synthesis of nitric oxide
      (NO) increased at the 0.5-Hz load; while decreasing at the 15% strain. With 10%
      strain, 1 Hz dynamic compression, the proliferation of chondrocytes and GAG
      synthesis increased and persisted for 7 days, and NO synthesis decreased at the
      third and seventh days of culture. CONCLUSIONS: This study showed that
      chondrocytes respond metabolically to compressive loading, which is expected to
      modulate the growth and the resultant biomechanical properties of these tissue
      engineered constructs during culture.

PMID- 18609519
TI  - Acetaminophen-induced acute liver failure treated with single-pass albumin
      dialysis: report of a case.
AB  - BACKGROUND: Acetaminophen (paracetamol) overdose is a leading cause of acute
      liver failure (ALF). When patients fulfill the King's College criteria for
      acetaminophen-induced ALF (AALF), they have a poor prognosis for survival without
      liver transplantation. Recent advances in artificial liver support have used
      albumin as a binding and scavenging molecule in ALF. One method, single-pass
      albumin dialysis (SPAD), involves dialyzing blood against an albumin-containing
      solution across a high-flux membrane to remove albumin-bound toxins. Herein, we
      describe our protocol for SPAD and report its use in a case of AALF as a bridge
      to native liver recovery. CASE: A 41-year-old female with no documented history
      of liver disease presented with acute acetaminophen toxicity and developed
      hepatic encephalopathy, coagulopathy and lactic acidosis. The patient met King's
      College criteria for liver transplantation, based on pH and INR, but was deemed
      not suitable as a candidate due to psychosocial comorbidities. On day 3 of her
      ICU admission, she received the first of five consecutive daily runs (total ~77
      hours) of SPAD. The patient's course was complicated by cerebral edema requiring
      mannitol. She was extubated on day 11 and transferred to the ward by day 13. At
      ICU discharge, her liver function (INR 1.9, bilirubin 435 mmol/L) and kidney
      function were recovering. She did not have any long-term neurological sequelae.
      By hospital discharge (day 46) her native liver function had recovered with a
      bilirubin <100mmol/L. CONCLUSION: We describe a case of a patient with
      acetaminophen-induced acute liver failure who was successfully bridged to
      spontaneous native liver recovery as a result of SPAD treatment. In patients with
      ALF, SPAD may be an additional intervention for temporary extracorporeal support.
      Further investigation in larger prospective studies is warranted.

PMID- 18609520
TI  - Rheopheresis in vascular diseases.

PMID- 18609521
TI  - Ulno-basilic arteriovenous fistulae: indications and surgical technique.
AB  - Ulnar-basilic fistula is a vascular access option for hemodialysis first reported
      in 1967. There is no inherent reason why the ulnar artery cannot be used to
      create a fistula at the wrist; however, a few reports dealing with its
      complications and survival rates have been published in the literature. In the
      present work the results of 9 ulnar-basilic fistulae done in 9 adults patients on
      chronic hemodialysis, are reported. Two fistulae were created as primary access
      and the remaining 7 fistulae as secondary access after thrombosis of an
      ipsilateral and controlateral radiocephalic fistula in 6 cases and in a case of
      high-flux brachiocephalic fistula. No episodes of surgical complications were
      observed. This fistula is an additional option to create a distal vascular access
      for hemodialysis before constructing a proximal access.

PMID- 18609522
TI  - Aneurysmorrhaphy is an easy technique for arteriovenous fistula salvage.
AB  - The life-saving procedures for patients in chronic renal failure (CRF) are
      hemodialysis (HD) or successful kidney transplantation. HD requires a properly
      placed and functioning vascular access, most often obtained by creating an
      arteriovenous fistula (AVF). The long-term patency of AVFs is limited, in
      addition to other factors, by the development of intimal hyperplasia and the
      process results in venous wall thickening and progressive fistula occlusion.
      Another problem is limited patency, due to the development of pseudoaneurysm,
      which is associated with an increased risk of thrombosis, infection and bleeding,
      difficult cannulation for dialysis, pain and cosmetic defects. Treatment is
      focused on rapidly progressing pseudoaneurysms, which can predispose to rupture,
      technical problems during cannulation because of pseudoaneurysm size or a growing
      intraluminal thrombus. Most of these patients are scheduled for pseudoaneurysm
      removal and new fistula construction or, occasionally, an endovascular procedure
      involving stent graft implantation. This paper describes a simple and inexpensive
      technique of managing an AVF pseudoaneurysm, i.e. aneurysmorrhaphy. To offset the
      weakening of the venous wall by suture following aneurysmorrhaphy, an external
      polyethylene terephthalate (PET) prosthesis was implanted in the vein to prevent
      the development of intimal hyperplasia in the de novo created AVF.

PMID- 18609523
TI  - Radiological central vein treatment in vascular access.
AB  - In the last decades, the percutaneous interventional approach for the treatment
      of central venous obstructions (CVO) has become increasingly popular as the
      treatment of first choice because of its minimal invasiveness and reported
      success rates. CVOs are caused by a diverse spectrum of diseases which can be
      broadly categorized into two principal eliciting genera, either benign or
      malignant obstructions. The large group of benign venous obstructions includes
      the increasing number of end-stage renal disease patients with vascular access
      related complications. Due to the invasiveness and complexity of thoracic surgery
      for benign CVOs, the less invasive percutaneous interventional therapy can
      generally be considered the preferred treatment option. Initially, the
      radiological intervention consisted of balloon angioplasty alone, subsequently
      additional stent placement was applied. This was advocated as either primary
      placement or secondary in cases of elastic recoil or residual stenosis after
      percutaneous transluminal angioplasty (PTA). The efficacy of angioplasty of CVO
      in patients with vascular accesses, either with or without stenting, has been
      addressed by various studies. Overall, reports indicate an initial technical and
      clinical success rate above 95% and satisfactory patency rates. However,
      systematic follow-up and frequent re-interventions are necessary to maintain
      vascular patency to achieve long-term success.

PMID- 18609524
TI  - Vena cava filters: a synopsis of complications and related topics.
AB  - Deep venous thrombosis and pulmonary embolism constitute common preventable
      causes of morbidity and mortality. The incidence of venous thromboembolism (VTE)
      continues to increase. Standard anticoagulation therapy may reduce the risk of
      fatal PE by 75% and that of recurrent VTE by over 90%. For patients who are not
      candidates for anticoagulation, a vena cava filter (VCF) may be beneficial.
      Despite a good overall safety record, significant complications related to VCF
      are occasionally seen. This review discusses both procedural and non-procedural
      complications associated with VCF placement and use. We will also discuss VCF use
      in the settings of pregnancy, malignancy, and the clinical need for more than one
      filter.

PMID- 18609525
TI  - A guideline misguided: a review of the 2006 KDOQI Guideline on
      surveillance/monitoring and prophylactic angioplasty of hemodialysis grafts.

PMID- 18609526
TI  - A response to 'a guideline misguided'.

PMID- 18609527
TI  - Transposed brachiobasilic fistula or PTFE arm graft - alternative or
      complementary?
AB  - PURPOSE: Our primary aims were (1) to examine the patency of transposed
      brachiobasilic (TBB) fistulae compared to arm arteriovenous graft (AVG) without
      prior transposition, and (2) to examine the patency of AVG with and without prior
      transposition. METHODS: Single institution; analysis of prospectively collected
      data between January 2001 and January 2007. Dedicated database and medical
      records were reviewed and results analyzed with SPSS. RESULTS: Ninety-one
      patients underwent 111 procedures (52 TBB: 39 AVG as index); 28 TBB failed with
      17 (60%) being replaced with an ipsilateral AVG. TBB compared to AVG (without
      prior TBB) had significantly (log rank <0.05 ) better primary, primary assisted
      and secondary patency. Secondary patency at 2 yrs was 47% to 33%, respectively.
      Ipsilateral AVG after TBB to primary AVG had superior patency rates (secondary
      patency at 2 yrs 52 vs. 33%) but did not reach significance (log rank =0.073).
      Combined secondary patency of TBB and AVG after TBB was 81% at 2 yrs.
      CONCLUSIONS: The TBB offers an autogenous fistula in the upper arm which has
      superior patency rates to an arm AVG. Once a TBB has failed an ipsilateral AVG is
      technically feasible and may offer better patency than a primary AVG.

PMID- 18609528
TI  - The Vascular Access Questionnaire: assessing patient-reported views of vascular
      access.
AB  - BACKGROUND: The use of central venous catheters for vascular access in
      hemodialysis (HD) patients is associated with an increased risk of complications
      compared to arteriovenous fistulas (AVF). Despite this, catheter use remains high
      and patient satisfaction may be an important driver of catheter use. METHODS: We
      developed the Vascular Access Questionnaire (VAQ) to measure patient-reported
      views of their vascular access. Chronic HD patients at two centers were asked to
      rate how bothered they were by 17 access-related problems. VAQ symptom scores
      were compared between patients using catheters and those using fistulas for
      vascular access. RESULTS: Two hundred and twenty-two patients were eligible for
      the study. Symptom score was not different between patients using catheters and
      those using fistulas (p=0.36). However, patients using fistulas were more likely
      to be at least moderately bothered by pain, bleeding, bruising, swelling, and the
      appearance of their access than patients using catheters. Elderly patients
      reported lower symptom scores with catheters than fistulas. CONCLUSIONS: Patients
      appear to be primarily concerned with the appearance of their access and
      cannulation-related complications, particularly the elderly. Better education
      about the risk of adverse events with catheters and the implementation of
      measures aimed at reducing cannulation-related complications may help to increase
      fistula rates and improve patient satisfaction with their vascular access.

PMID- 18609529
TI  - A successful scheme for reducing waiting times for arteriovenous fistula
      formation.
AB  - PURPOSE: In a bid to reduce waiting times for arteriovenous fistula (AVF)
      formation we introduced a scheme whereby nephrologists were able to place
      patients directly on the waiting list for surgery. This study evaluated the
      quality of these direct referrals and assessed the reduction in waiting times.
      METHODS: Fifty consecutive patients referred directly to the waiting list were
      compared with 50 patients placed on the waiting list after being assessed in our
      vascular access clinic. RESULTS: Forty-nine patients from the direct group and 47
      patients from the clinic group underwent surgery. In the direct group 39 patients
      (80%) underwent the same procedure as they had been originally listed for,
      compared with 39 patients (83%) in the clinic group (p=0.80). A fistula suitable
      for needling was created in 37 patients (76%) of the direct group and 38 patients
      (81%) of the clinic group (p=0.62). The median wait from referral to surgery in
      the direct group was significantly lower than in the clinic group (62 vs.141
      days; p<0.0001). CONCLUSION: This study demonstrates that nephrologists are able
      to effectively assess select patients for AVF formation. This significantly
      reduces waiting times for surgery, without an increase in cancelled operations,
      or a reduction in technical success.

PMID- 18609530
TI  - The effect of hemoglobin level on arteriovenous fistula survival in Iranian
      hemodialysis patients.
AB  - OBJECTIVE: End-stage renal disease (ESRD) poses steadily growing challenges to
      health care systems worldwide. Renal replacement therapy with hemodialysis (HD)
      or kidney transplantation is the only possibility for ESRD patient survival. A
      complete correction of anemia in HD patients may lead to an increased risk of
      vascular arteriovenous fistula (AVF) primary failure; some studies have
      demonstrated that decreased levels of hemoglobin (Hb) had adverse effects on
      cardiac and brain function. This study was designed to evaluate the impact of
      different risk factors, especially the Hb level on AVF survival. METHODS:
      Prospective observational data were analyzed from a non-randomized sample (n=100)
      of HD patients who were referred for first AVF creation between April 2005 and
      December 2006 with <1 month on HD. The relative risk (RR) of access primary
      failure was evaluated in four different groups of patients divided according to
      their Hb levels (<8, 8-10, 10-12, and >12 g/dL). Other factors possibly
      influencing vascular access (VA) survival were also considered including gender,
      age, smoking, diabetes, hypertension, parathyroid hormone levels, ACE inhibitor
      intake and triglyceride levels. The analyses were performed using SPSS v.11.5,
      Kaplan-Meier analysis, Cox's regression and log rank test. RESULTS: There was a
      statistically significant higher risk of AVF primary failure in patients with Hb
      <8 g/dL (RR=1.41; p=0.01), diabetes (RR=1.21; p=0.05), age>60 yrs (RR=1.41;
      p=0.06) were identified as predictive factors for AVF primary failure. ACE
      inhibitor intake (RR=0.45; p=0.01) was found to be protective. CONCLUSION:
      Correction of serum Hb level can lead to a better result in VA survival and ACE
      inhibitor intake was found to be a protective factor.

PMID- 18609531
TI  - Ultrasound-guided direct basilic-axillary approach in preoperative venography for
      hemodialysis access.
AB  - PURPOSE: Hemodialysis patients with suspected central vein stenosis or occlusion
      require venographic assessment before access surgery. Conventional venography may
      be unsatisfactory because of the limited ability to image central veins via
      peripheral arm veins that are inadequate or that have been damaged by multiple
      cannulations. Imaging of the central veins requires high flow contrast injection,
      which may be unattainable through small peripheral veins. We suggest a simple
      technique to improve central vein imaging by ultrasound-guided direct puncture of
      the basilic vein at its entry to the axilla. METHODS: We studied 20 patients in
      whom upper limb venography via peripheral veins was inadequate for the
      satisfactory demonstration of central vein anatomy and they underwent direct
      basilic-axillary vein puncture with Doppler ultrasound guidance. A 4Fr
      micropuncture catheter was used for manual injection of the contrast agent to
      image the central veins. RESULTS: All patients had inadequate upper limb
      venography via peripheral vein cannulation, and stenosis could not be ruled out
      due to poor visualization of the central veins. In all cases, venography by
      Doppler ultrasound-guided direct basilic-axillary vein puncture was very easy for
      both the radiologist and the patient, consistently providing high quality imaging
      without the need for repeated attempts at cannulation and without the need for
      infusion pumps. No complications were noted during or after the procedure.
      CONCLUSIONS: Venography by Doppler ultrasound-guided direct basilic-axillary vein
      puncture is a simple and rapidly performed technique that improves the
      visualization of the central veins.

PMID- 18609532
TI  - Plasminogen activator inhibitor-1 activity and 4G/5G polymorphism in
      hemodialysis.
AB  - INTRODUCTION: Chronic insufficiency alters homeostasis, in part due to
      endothelial inflammation. Plasminogen activator inhibitor-1 (PAI-1) is increased
      in renal disease, contributing to vascular damage. We assessed PAI-1 activity and
      PAI-1 4G/5G polymorphism in hemodialysis (HD) subjects and any association
      between thrombotic vascular access (VA) events and PAI-1 polymorphism. METHODS:
      Prospective, observational study in 36 HD patients: mean age: 66.6 +/- 12.5 yr,
      males n=26 (72%), time on HD: 28.71 +/- 22.45 months. Vascular accesses: 10
      polytetrafluoroethylene grafts (PTFEG), 22 arteriovenous fistulae (AVF), four
      dual lumen catheters (CAT). Control group (CG): 40 subjects; mean age: 60.0 +/-
      15 yrs, males n=30 (75%). Group A (GA): thrombotic events (n=12), and group B
      (GB): No events (n=24). Groups were no different according to age (69.2 +/- 9.12
      vs. 65.3 +/- 14.5 yrs), gender (males: 7; 58.3% vs. 18; 81.8%), time on HD (26.1
      +/- 14.7 vs. 30.1 +/- 38.7 months), causes of renal failure. Time to follow-up
      for access thrombosis: 12 months. RESULTS: PAI-1 levels in HD: 7.21 +/- 2.13 vs.
      CG: 0.42 +/- 0.27 U/ml (p<0.0001). PAI-1 4G/5G polymorphic variant distribution
      in HD: 5G/5G: 6 (17%), 4G/5G: 23 (64%); 4G/4G: 7 (19%) and in CG: 5G/5G: 14
      (35%); 4G/5G: 18 (45%); 4G/4G: 8 (20%). C-reactive protein (CRP) in HD: 24.5 +/-
      15.2 mg/L vs. in CG 2.3 +/- 0.2 mg/L (p<0.0001). PAI-1 4G/5G variants: GA: 5G/5G:
      3; 4G/5G: 8; 4G/4G: 1; GB: 5G/5G: 3; 4G/5G: 15; 4G/4G: 6. Thrombosis occurred in
      8/10 patients (80%) with PTFEG, 3/22 (9%) in AVF, and 1/4 (25%) in CAT. Among the
      eight PTFEG patients with thrombosis, seven were PAI 4G/5G. CONCLUSIONS: PAI-1
      levels were elevated in HD patients, independent of their polymorphic variants,
      4G/5G being the most prevalent variant. Our data suggest that in patients with
      PTFEG the 4G/5G variant might be associated with an increased thrombosis risk.

PMID- 18609533
TI  - Atrial thrombosis: a near fatal complication of a Portacath.
AB  - Portacaths (Bard Medical Division, Georgia, USA) are routinely used for central
      venous access in patients with poor peripheral veins who require regular long
      term venous access. Complications associated with central venous access devices,
      including infection and thrombosis, are well described in the literature;
      however, to our knowledge there have been few case reports of right atrial
      thrombi and pulmonary emboli related to implanted ports. This paper discusses the
      case of a patient who developed an atrial thrombosis 4 months after port
      placement and subsequent pulmonary emboli.

PMID- 18609535
TI  - Improved activity retention of enzymes deposited on solid supports.
AB  - Enzymes deposited on solid support usually show good stability when operated in
      organic solvents. Decreased stability of the enzyme preparations was noticed when
      low enzyme loadings were used (e.g., with Celite as support; less than 1 mg
      enzyme/g). It was possible to avoid the activity loss by the addition of an
      additive which protects the enzyme during the immobilization. Proteins (such as
      albumin, gelatin, and casein) and poly(ethylene glycol) were effective additives
      whereas amino acids, monomeric carbohydrates, and polysaccharides had no effect.
      The amount of additive needed for stabilization was shown to depend on the
      structure of the support, more additive being required for a support with high
      porosity. The stabilizing effect was investigated in a series of glyceryl
      controlled-pore glass (CPG) with varying specific surface areas (9.5-180 m(2)/g).
      The minimum addition of albumin, giving full stabilization, on the different
      supports correlated to a monolayer coverage of the surface, approximately 2-3 mg
      protein/m(2). The effect of the additive was less pronounced when increasing
      amounts of enzyme were immobilized (5-40 mg enzyme/g Celite). The effect of the
      additives was studied using mandelonitrile lyase, but alpha-chymotrypsin and
      lipase P were also shown to be stabilized.

PMID- 18609536
TI  - Cultivation of mammalian cells as aggregates in bioreactors: effect of calcium
      concentration of spatial distribution of viability.
AB  - Recombinant human kidney epithelial 293 cells were cultivated as aggregates in
      suspension. The concentration calcium ion, in the range of 100 muM to 1mM,
      affected the rate of aggregate formation. During the course of cultivation the
      size distribution of aggregates shifted and the fraction of larger aggregates
      increased. This effect was more profound in cultures with a high calcium
      concentration. Scanning and transmission microscopic examination of the
      aggregates revealed that cell packing was greater in the high calcium cultures
      and that ultrastructural integrity was retained in aggregates from both low and
      high calcium cultures. Confocal microscopy was applied to examine the viability
      of cells in the interior of the aggregates. High viability was observed in the
      aggregates obtained from exponentially growing cultures. Aggregates from the high
      calcium culture in the stationary phase exhibited lower viability in the
      interior. With its ease of retention in a perfusion bioreactor, aggregate
      cultures offer an alternative choice for large-scale operation.

PMID- 18609537
TI  - Cell-cell adhesion and aggregation: Influence on the growth behavior of CHO
      cells.
AB  - The influence of cell-cell adhesion on the growth behavior of Chinese hamster
      ovary (CHO) cells in suspension culture was investigated. CHO cells form
      aggregates under suboptimal growth conditions. Clusters are formed around
      decaying and dead cells. The deoxyribonucleic acid (DNA) released from these
      cells was found to mediate the cells was found to mediate the cell-cell adhesion.
      Cluster formation dramatically influenced the growth behavior of the cells.
      First, cells within aggregates showed a strongly reduced specific proliferation
      rate, and second, shear forces exerted on large aggregates caused a considerable
      higher specific death rate than those exerted on single cells. These factors led
      to a reduction of the specific growth rate up to 50%. This decrease could be
      avoided by addition of DNase 1 to the medium. It is shown that the separate
      determination of the specific proliferation and death rates is not feasible with
      state-of-the-art methods. To achieve a more profound and precise description of
      the growth pattern of animal cells, we propose an extended Monod model and
      describe the relevant methods.

PMID- 18609538
TI  - Evaluation of a hepatocyte-entrapment hollow fiber bioreactor: a potential
      bioartificial liver.
AB  - We have developed a hepatocyte entrapment hollow fiber bioreactor for potential
      use as a bioartificial liver. Hepatocytes were entrapped in collagen gel inside
      the lumen of the hollow fibers. Medium was perfused through the intraluminal
      region after contraction of the hepatocyte-entrapment gel. Another medium stream,
      comparable to the patient's blood during clinical application, passed through the
      extracapillary space. Viability of hepatocytes remained high after 5 days as
      judged by the rate of oxygen uptake and viability staining. Urea and albumin
      synthetic activities were also sustained. Transmission electron microscopic
      examination demonstrated normal ultrastructural integrity of hepatocytes in such
      a bioreactor. With its sort-term, extracorporeal support of acute liver failure,
      the current bioreactor warrants further investigation.

PMID- 18609539
TI  - Immobilization of lipase for effective interesterification of fats and oils in
      organic solvent.
AB  - In order to investigate quantitatively the interesterification reaction, triolein
      and stearic acid were used as substrates and eight commercially available lipases
      were tested for their suitability for the reaction. Three fungal lipase
      preparations were found to be suitable. The hydrolytic activity of the commercial
      lipases was tested with olive oil, and it was noted that there was no correlation
      between their hydrolytic and interesterification activities. Among the lipases
      tested, Mucor miehei lipase was chosen for further study because of it high
      protein content and its relatively high hydrolytic and interesterification
      activities, both of which are required for effective interesterification. The
      effect of water activity of the interesterification reaction was investigated.
      interesterification activity was shown to be maximum at the water activity of
      0.25. As the water activity of the lipase increased, hydrolysis of triglyceride
      was accelerated. At zero water activity, high conversion was achieved, although
      interesterification activity was relatively lower than that at the water activity
      of 0.25. A new and simple immobilization method was developed in order to render
      hydrophobicity to the lipase and hence to improve the interesterification
      activity of the lipase. The lipase was immobilized covalently with glutaraldehyde
      or with six alkyl chains as spacers onto Florisil (magnesium silicate, a
      inorganic matrix). Interesterification activity of the immobilized lipase with
      the hydrophobic spacers were increased against that of re lipase. The increase of
      activity was up to 8-fold that of the original activity of free lipase when the
      spacer was 7-aminoheptanoic acids. Relatively high stability of the immobilized
      lipase was shown in a continuous packed bed column reactor with a half-life of 97
      days.

PMID- 18609540
TI  - Plasmid retention and gene expression in suspended and biofilm cultures of
      recombinant Escherichia coli DH5alpha(pMJR1750).
AB  - Differences in plasmid retention and expression are studied in both suspended and
      biofilm cultures of Escherichia coli DH5alpha(PMJR1750). An alternative
      mathematical model is proposed which allows the determination of plasmid loss
      probability in both suspended batch and continuously fed biofilm cultures. In our
      experiments, the average probability of plasmid loss of E. coli
      DH5alpha(pMJR1750) is 0.0022 in batch culture in the absence of antibiotic
      selection pressure and inducer. Under the induction of 0.17 MM IPTG, the maximum
      growth rate of plasmid-bearing cells in suspended batch culture dropped from 0.45
      h(-1) to 0.35 h(-1) and the beta-galactosidase concentration reached an
      experimental maximum of 0.32. pg/cell 4 hours after the initiation of induction.
      At both 0.34 and 0.51 mM IPTG, growth rates in batch cultures decreased to 0.16
      h(-1), about 36% of that without IPTG, and the beta-galactosidase concentration
      reached an experimental maximum of 0.47 pg/cell 3 hours after induction.In
      biofilm cultures, both plasmid-bearing and plasmid-free cells in increase with
      time reaching a plateau after 96 hours n the absence of both the inducer and any
      antibiotic selection pressure. Average probability of plasmid loss for biofilm
      bound E. coli DH5beta(pMJR1750) population was 0.017 without antibiotic
      selection. Once the inducer IPTG was added, the concentration of plasmid-bearing
      cells in biofilm dropped dramatically while plasmid-free cell numbers maintained
      unaffected. The beta-galactosidase concentration reached a maximum in all biofilm
      experiments 24 hours after induction; they were 0.08, 0.1, and 0.12 pg/cel under
      0.17, 0.34, and 0.51 mM IPTG, respectively.

PMID- 18609541
TI  - Defined media optimization for growth of recombinant Escherichia coli X90.
AB  - An optimized, defined minimal medium was developed to support balanced growth of
      Escherichia coli X90 harboring a recombinant plasmid. Foreign protein expression
      was repressed in these studies. A pulse injection technique was used to identify
      the growth responses to nutrients in a chemostat. Once the nutrients essential
      for growth had been identified, the yield coefficients for individual medium
      components. These yield coefficients were used to develop an optimized, glucose
      limited defined minimal medium that supports balanced cell growth in chemostat
      culture. The biomass and substrate concentrations follow the Monod chemostat
      model. The maximum specific growth rate determined in a washout experiment is
      0.87 h(-1) for this strain in the optimized medium. the glucose yield factor is
      0.42 g DCW/g glucose and the maintenance coefficient is zero in the glucose
      limited chemostat culture.

PMID- 18609542
TI  - Immobilized catalase: deactivation and reactor stability.
AB  - The quasi-steady behavior of a continuous flow reactor in which hydrogen peroxide
      is decomposed by immobilized catalase is investigated. Under certain conditions,
      reactors involving such substrate-inhibited, self-poisoning reactions are
      susceptible to sudden failure and the reactor moves catastrophically from high-
      to low-conversion quasi-steady states. This exchange-of-steady-states phenomenon
      is examined in the light of experimental evidence for the enzyme catalase from
      bovine liver.

PMID- 18609543
TI  - Production of the siderophore enterobactin: use of four different fermentation
      systems and identification of the compound by HPLC.
AB  - The article describes four different fermentation procedures for Escherichia coli
      AN311, a producer of enterobactin. A regular rotary shaker culture with a
      biphasic system consisting of an agar layer (as a reservoir for feeding
      processes) and a layer of liquid medium, 2.4 L and 10 L batch cultures, and a
      novel dialysis membrane fermentor were used. With the use of this latter
      fermentor type, the production of enterobactin could be increased by a factor of
      about 9.5, while growth increased by a factor of 12 compared to the other
      systems. For the rapid and reliable quantification of the concentration and
      purity of enterobactin an analytical and preparative high-performance liquid
      chromatography (HPLC) method was established. The degradation compounds of this
      siderophore were detected by diodearray and bioassays. A comparison of total
      catechol production as well as the distribution between enterobactin and its
      degradation compounds is given.

PMID- 18609544
TI  - In vitro production of Bombyx mori silk fibroin by organ culture of the posterior
      silk glands; isotope labeling and fluorination of the silk fibroin.
AB  - An in vitro silk fibroin production system has been developed by culture of
      posterior silk glands from Bombyx mori. A large amount of the silk fibroin was
      produced continuously and effectively with a rotation culture procedure. Modified
      Grace's insect medium was used, and oxygen bubbling in the medium was performed.
      In addition, half of the medium was replaced with fresh medium every 6 h. The
      production yield of silk fibroin produced after 100 h culture was 81 mg/g wet
      weight of posterior silk gland. This culture system was used successfully for
      efficient (15)N isotope labeling of silk fibroin, which is required for (15)N
      solid state nuclear magnetic resonance (NMR) analysis of silk fibroin. Moreover,
      the introduction of fluorinated amino acids into silk fibroin was also carried
      out using this culture system.

PMID- 18609545
TI  - Scaleup of ajmalicine production by plant cell cultures of Catharanthus roseus.
AB  - The effect of scaleup on he production of ajmalicine by a Catharanthus roseus
      cell suspension culture in a selected induction medium were studied. In
      preliminary experiments it was observed that the culture turned brown and the
      production was inhibited upon transfer from a shake flask to a stirred bioreactor
      with forced aeration. Two factors were recognized as the potential origin of the
      differences between shake flask and bioreactor cultures: gas composition and
      mechanical shear forces. These factors were studied separately.By recirculating a
      large part of the exhaust gas, a comparable gas regime was obtained in a
      bioreactor as occurred in a shake flask cultures. This resulted in the absence of
      browning and a similar pattern of ajmalicine production as observed in shake
      flasks. The effect of shear forces could not be demonstrated. However, the
      experiments showed that the culture may be very sensitive to liquid phase
      concentrations of gaseous compounds. The effects of k(L)a, aeration rate, CO(2)
      production rate, and influent gas phase CO(2) concentration on the liquid phase
      CO(2) concentration are discussed.

PMID- 18609546
TI  - Continuous bioconversion of n-octane to octanoic acid by recombinant Escherichia
      coli (alk(+)) growing in a two-liquid-phase Chemostat.
AB  - Escherichia coli is able to grow on sugars in the presence of a bulk n-alkane
      phase. When E. coli is equipped with the alk genes from Pseudomonas oleovorans,
      the resulting recombinant strain converts n-alkanes into the corresponding
      alkanoic acids. To study the effects of growth rate and exposure to a bulk apolar
      phase on the physiology and the productivity of E. coli, we have grown this
      microorganism in two-liquid-phase continuous cultures containing 5% (v/v) n
      octane.In contrast to batch cultures of wild-tape E. coli grown in the presence
      of n-octane, cells remained viable during the entire continuous culture, which
      lasted 200 h. Bioconversion of n-octane to n-octanoic acid by a recombinant E.
      coli (alk(+)) in a two-liquid-phase continuous culture was made possible by
      optimizing both the recombinant host strain and the conditions of culturing the
      organism. Continuous production in such two-phase systems has been maintained for
      the least 125 h without any changes in the product concentration in the
      fermentation medium. The volumetric productivity was determined as a function of
      growth rate and showed a maximum at a dilution rate D = 0.32 h(-1), reaching a
      continuous production rate of 0.5 g octanoate/L . h (4 tons/m(3) . year).

PMID- 18609547
TI  - Kinetics of cell growth and heterologous glucoamylase production in recombinant
      Aspergillus nidulans.
AB  - In the work, a study of cell growth and the regulation of heterologous
      glucoamylase synthesis under the control of the positively regulated alcA
      promoter in a recombinant Aspergillus nidulans is presented. We found that
      similar growth rates were obtained for both the host and recombinant cells when
      either glucose or fructose was employed as sole carbon and energy source. Use of
      the potent inducer cyclopentanone in concentrations greater than 3 mM resulted n
      maximum glucoamylase concentration and maximum overall specific glucoamylase
      concentration over 80 h of batch cultivation. However, cyclopentanone
      concentrations in excess of 3 mM also showed an inhibitory effect on spore
      germination as well as fungal growth. In contrast, another inducer, threonine,
      had no negative effect on spore germination even when concentrations of up to 100
      mM were used with either glucose or fructose as carbon source. Glucoamylase
      synthesis in the presence of glucose plus either inducer did not begin until
      glucose was totally depleted, suggesting strong catabolite repression. Similar
      results were obtained when fructose was employed, although low levels of
      glucoamylase were detected before fructose depletion, suggesting partial
      catabolite repression. The highest enzyme concentration (570 mg/L) and overall
      specific enzyme concentration (81 mg/g cell) were observed in batch culture when
      cyclopentanone was the inducer and fructose the primary carbon source. A maximum
      glucoamylase concentration of 1.1 g/L and an overall specific glucoamylase
      concentration of 167 mg/g cell were obtained in a bioreactor using cyclopentanone
      as the inducer and limited-fructose feeding strategy, which nearly doubles the
      glucoamylase productivity from batch cultures.

PMID- 18609548
TI  - Adsorption of BSA on QAE-dextran: equilibria.
AB  - Equilibrium isotherms for adsorption of bovine serum albumin (BSA) on a strong
      base (QAE) dextran-type ion exchanger have been determined experimentally. They
      were not affected by the initial concentration of BSA but were affected by pH
      considerably. They were correlated by the Langmuir equation when pH > or = 5.05
      and by the Freundlich equation of pH 4.8, which is close to pl approximately 4.8
      of BSA. The contribution of ion exchange to adsorption of BSA on the ion
      exchanger was determined experimentally. The maximum amounts of inorganic anion
      exchanged for BSA were 1% and 0.4% of the exchange capacity of the ion exchanger
      at pH 6.9, respectively. Since the effect of the ion exchange on the adsorption
      appeared small, BSA may be adsorbed mainly by electrostatic attraction when pH >
      or = 5.05 and by hydrophobic interaction or hydrogen bonding at pH 4.8. When NaCl
      coexisted in the solution, the shape of the isotherm was similar to the Langmuir
      isotherm, but it is shifted to the right. When the concentration of NaCl was 0.2
      mol/dm(3), BsA was not adsorbed on the resin. When BSA was dissolved in pure
      water, the saturation capacity of BSA on HPO(4) (2-),-form resin was about 2
      times larger than that for adsorption from the solution with buffer (pH 6.9 and
      8.79). The saturation capacity for adsorption of BSA in pure water on HPO(4) (2-)
      + H(2)O(4) (-)-from resin was much smaller than that from the solution with
      buffer. The isotherms for univalent Cl(-)-and H(2)PO(4) (-)-form resin was
      peculiar; that is, the amount of BSA adsorbed decreased with increasing the
      liquid-phase equilibrium concentration of BSA.

PMID- 18609549
TI  - A cohort mortality study of chemical laboratory workers at Department of Energy
      Nuclear Plants.
AB  - OBJECTIVE: This study evaluates the mortality experience of 6,157 chemical
      laboratory workers employed at United States Department of Energy facilities.
      METHODS: All cause, all cancer and cause-specific standardized mortality ratios
      were calculated. Cox regression analyses were conducted to further evaluate the
      relation between chemical exposure and mortality risk due to selected cancers.
      RESULTS: The mortality due to all causes combined and all cancers combined were
      below expectation for the cohort. There were no statistically significant
      elevations reported among males for any specific cancer or non-cancer outcome.
      There no statistically significant elevations among females for any specific non
      cancer and most specific cancers; however, multiple myeloma deaths were
      significantly elevated (SMR = 3.56; 95% CI = 1.43-7.33; number of observed
      deaths, n = 7). Statistically significant elevations were seen among workers
      employed 20+ years for leukemia using both 2- and 5-year lag periods. Also, a
      statistically significant positive trend of elevated lung cancer mortality with
      increasing employment duration was seen using both 5- and 10-year lags. A similar
      trend was seen for smoking related cancers among men. CONCLUSION: While lymphatic
      and hematopoietic cancer mortality was below expectation, a significant elevation
      of multiple myeloma deaths among females and an elevation of leukemia among
      workers employed 20+ years (possibly due to radiation and benzene exposure) were
      observed. A NIOSH case-control study is underway to examine more closely the
      relation between multiple myeloma and a variety of chemical exposures among
      workers employed at the Oak Ridge K-25 facility.

PMID- 18609550
TI  - New look at the old management of unknown primary.

PMID- 18609552
TI  - Industrial separation of carboxylic and amino acids by liquid membranes:
      applicability, process considerations, and potential advantage.
AB  - Liquid-liquid extraction and membrane separation are well-known separation method
      of extensive industrial application. Their incorporation into liquid membranes
      has the potential of several advantages, some of which are of particular interest
      for the recovery of carboxylic and amino acids: selectivities higher than those
      attainable by current separation methods, saving on energy costs for final
      concentration of separated products, high fluxes, compact installation, and low
      capital and operation costs. Stability of the liquid advantages, can be secured
      by utilizing extractant blocking polymeric membranes, Applicability, process
      consideration, and economic implications for recovery for carboxylic and amino
      acids by various extractant/membrane combinations are discussed.

PMID- 18609553
TI  - Measurement of hydrodynamic shear by using a dissolved oxygen probe.
AB  - When a dissolved oxygen (DO) probe is submerged in an air-saturated cell culture
      medium the thickness of the liquid film that exists outside the membrane of a DO
      probe changes with hydrodynamic shear. The response of the DO probe thus varies
      with the hydrodynamic shear environment near the DO probe in cell culture
      reactors. The thickness of the liquid film was estimated by using a three-layer
      model, which describes the flow of DO molecules through the liquid layer, the
      membrane, and the electrolyte, to the cathode of a DO probe. According to the
      three-layer model, the current output of the DO probe was a strong function of
      thickness of the liquid film outside the membrane of the DO probe. A correlation
      between shear rates on the surface of the probe and the DO saturation reading was
      obtained by using two concentric cylinders with a rotating inner cylinder. This
      correlation was then used to characterize the local hydrodynamic shear
      environment in a cell culture reactor.

PMID- 18609554
TI  - Biological sulfuric acid transformation: Reactor design and process optimization.
AB  - As an alternative to the current disposal technologies for waste sulfuric acid, a
      new combination of recycling processes was developed. The strong acid (H(2)SO(4))
      is biologically converted with the weak acid (CH(3)COOH) into two volatile weak
      acids (H(2)S, H(2)CO(3)) by sulfate-reducing bacteria. The transformation is
      possible without prior neutralization of the sulfuric acid. The microbially
      mediated transformation can be followed by physiochemical processes for the
      further conversion of the H(2)S.The reduction of sulfate to H(2)S is carried out
      under carbon-limited conditions at pH 7.5 to 8.5. A fixed-bed biofilm column
      reactor is used in conjunction with a separate gas-stripping column which was
      installed in the recycle stream. Sulfate, total sulfide, and the carbon substrate
      (in most cases acetate) were determined quantitatively. H(2)S and CO(2) are
      continually removed by stripping with N(2). Optimal removal is achieved under pH
      conditions which are adjusted to values below the pK(a)-values of the acids. The
      H(2)S concentration in the stripped gas was 2% to 8% (v/v) if H(2)SO(4) and
      CH(3)COOH are fed to the recycle stream just before the stripping
      column.Microbiol conversion rates of 65 g of sulfate reduced per liter of
      bioreactor volume per day are achieved and bacterial conversion efficiencies for
      sulfate of more than 95% can be maintained if the concentration of undissociated
      H(2)S is kept below 40 to 50 mg/L. Porous glass spheres, lava beads, and
      polyurethane pellets are useful matrices for the attachment of the bacterial
      biomass. Theoretical aspects and the dependence of the overall conversion
      performance on selected process parameters are illustrated in the Appendix to
      this article.

PMID- 18609555
TI  - Relieving effects of glycine and methionine from acetic acid inhibition in
      Escherichia coli fermentation.
AB  - Among amino acids screened for their potential to relieve wild and recombinant
      Escherichia coli from the negative effects of acetic acid, glycine, and
      methionine showed a sparing effect. In the presence of 2 g/L of acetic acid,
      addition of 0.5 g/L of glycine or methionine resulted in either a complete
      recovery or a further enhancement in the specific growth rate, while the
      enhancement was significant but not fully complete in the presence of 4 g/L of
      acetic acid. The addition of 0.5 g/L of methionine alleviated the negative effect
      of acetic acid on recombinant E. Coli growth to produce more beta-lactamase,
      which was encoded by plasmid pUC18. In continuous fermentation the methionine
      effect on recombinant. E. coli metabolism depended on dilution rate; at high
      dilution rates, above 0.4 h(-1), the methionine addition enhanced beta-lactamase
      production and reduced acetic acid formation, while at low dilution rates, below
      0.3 h (-1), the effect was reversed. In def-batch fermentation with wild-type E.
      Coli, cell growth rate and cell yield from glucose were enhanced with methionine
      addition, while the acetic acid concentration reached over 4 g/L.

PMID- 18609556
TI  - Plasmid burden in chemostat culture of Escherichia coli: Its effect on the
      selection for overproducers of host enzymes.
AB  - The effect of plasmid-mediated metabolic burden of on the expression of the host
      genes and its consequences on the plasmid maintenance were studied in carbon
      limited chemostat culture of Escherichia coli 1EA(pBR322) subject to selection
      for strains overproducing chromosomally coded ribitol dehydrogenase. The
      chemostat population became rapidly heterogeneous and the competition among
      evolved strains was found to be crucial for the kinetics of the plasmid loss from
      the culture. The selective disadvantages in growth rate associated with plasmid
      carriage in the parent-like and ribitol dehydrogenase-overproducing strains was
      estimated.

PMID- 18609557
TI  - Cell Culture conditions determine the enhancement of specific monoclonal antibody
      productivity of calcium alginate-entrapped S3H5/gamma2bA2 hybridoma cells.
AB  - Immobilization offers several intrinsic advantages over free suspension cultures
      for the production of monoclonal antibodies. An important advantage of
      immobilization is the improved specific monoclonal antibody (MAb) productivity
      (q(MAb)) that can be obtained. However, there are conflicting reports in the
      literature on the enhancement of the q(MAb) with immobilization. The
      discrepancies between these reports can be attributed to the different to either
      the cultivation methods used for immobilized cell or to difference between the
      cell lines used in the various studies. We show that these differences may be
      attributed to the different cultivation methods used for one model hybridoma cell
      line. S3H5/gamma2bA2 hybridoma cells entrapped in different sizes of calcium
      alginate beads were cultivated in both T- and spinner flasks in order to
      determine whether cultivation methods (T- and spinner flasks) and bead size
      influence the q(MAb) Free-suspended cell cultures inoculated with cells recovered
      from alginate beads were also carried out in order to determine whether changes
      in the q(Mab) of the entrapped cells are reversible.The cultivation methods was
      found to influence significantly the q(MAb) of the entrapped cells. When the
      entrapped cells in 1-mn diameter beads were cultivated in T-flasks, the q(MAb)
      was not increased by 200% as previously observed in an entrapped cell culture
      using 1-mm-diameter alginate beads in spinner flasks. The q(MAb) of the entrapped
      cell was approximately 58% higher than that of the free-suspended cells in a
      control experiment. Unlike the cultivation method, the bead size in the range of
      1- to 3-mm diameter did not significantly influence the q(MAb), regardless of
      cultivations methods. The changes in q(MAb) of an entrapped cells were
      reversible. When the free-suspended cells recovered from the T- and spinner
      flasks were sub-cultured in T- and spinner flasks enhanced q(MAb) of the
      entrapped cells in both cases decreased to the level of the free-suspended cell
      in a control experiments. Taken together, these results shows that the method of
      cultivation of hybridoma cells immobilized in alginate beads determines the
      extent of enhancement of the q(MAb).

PMID- 18609558
TI  - Formation of microparticulate protein powder using a supercritical fluid
      antisolvent.
AB  - Gas antisolvent (GAS) expansion of dimethylsulfoxide (DMSO) and N,N
      dimethylformamide (DMFA) solutions with supercritical carbon dioxide was used to
      produce biologically active powders of insulin. Powders with 90% of the particles
      smaller than 4 mum and 10% smaller than 1 mum were obtained under all conditions
      tested when the process was operated continuously, with small liquid droplets
      sprayed into a flowing supercritical continuum. Slow pressurization of the
      stagnant protein solution resulted in larger particles. In vivo tests on rats
      revealed no differences between the biological activity of processed and
      unprocessed insulin, GAS processing of organic solution appears to be a reliable
      and effective method for the production of dry, biologically active
      microparticulate powders of peptides and proteins.

PMID- 18609559
TI  - Startup of anaerobic fluidized bed reactors with acetic acid as the substrate.
AB  - The startup of anaerobic fluidized bed reactors, which use Manville R-633 beads
      as the growth support media, acetate enriched bacterial culture as the inoculum,
      and acetic acid as the sole substrate, is studied. Tow startup strategies are
      evaluated: one based on maximum and stable substrate utilization and another
      based on maximum substrate loading controlled by reactor pH. The startup process
      is characterized using a number of operational parameters.The reactors again
      excellent total organic carbon (TOC) removal (i.e., > 97% at a feed concentration
      of 5000 mg TOC/L) and stable methane production (i.e., 0.90 L CH(4)/g TOC, where
      TOC(r) is TOC removed) at a early stage of the startup process, regardless of the
      strategies applied. The loading can be increased rapidly without the danger of
      being overloaded. Significant losses of growth support media and biomass caused
      by gas effervescence at higher loadings limits the maximum loading that can be
      safely applied during startup process.A high reactor immobilized biomass
      inventory is achievable using the porous growth support media (e.g., Manville 633
      beads). A rapid increase in loading creates a substrate rich environment that
      yields more viable reactor biomass. Both substrate utilization rate (batch and
      continuous) and immobilized biomass inventory stabilize concomitantly at the late
      stage of the startup process, indicating the attainment of steady-state
      conditions in reactors. Therefore, they are better parameters that TOC removal
      and methane production for characterizing the entire startup process of aerobic
      fluidized bed reactor.The strategy based on maximum substrate loading controlled
      by reactor pH significantly shortens the startup time. In this case, the reactor
      attains steady-state conditions approximately 140 days after startup. On the
      other hand, a startup time of 200 days is required when the strategy based
      maximum substrate utilization is adopted.

PMID- 18609560
TI  - Mass transport parameters of aspen wood chip beds via stimulus-response tracer
      techniques.
AB  - A stimulus-response tracer technique has been used to characterize packed beds of
      untreated, as well as acid prehydrolyzed, and enzymatically hydrolyzed aspen wood
      chips. Glucose was used as the tracer. Bulk liquid phase dispersion, interphase
      mass transfer, and intraparticle diffusion coefficients were determined for these
      materials as well as effective porosities and tortuosities. The untreated and
      prehydrolyzed aspen wood chips were found to have effective coid fractions of ca.
      0.8, while the enzymatically hydrolyzed wood chips exhibited a void fraction of
      0.37. Intraparticle diffusion was approximately twice as rapid in the
      prehydrolyzed and enzymatically hydrolyzed wood chips as in the untreated wood
      chips. Also, under the current experimental conditions, intraparticle diffusional
      transport resistance accounted for roughly half of the total tracer pulse
      dispersion. It is demonstrated that stimulus-response tracer techniques can be
      useful and convenient probes for beds of lignocellulosic, or other conversion
      and/or treatment.

PMID- 18609561
TI  - Application of gravitational sedimentation to efficient cellular recycling in
      continuous alcoholic fermentation.
AB  - A mathematical model for the sedimentation velocity in an inclined parallel plate
      sedimenter is proposed. The parameters of the alcoholic fermentation broth (cell
      density of Saccharomyces cerevisiae, density of the fermentation medium,
      viscosity of the broth at various alcohol and biomass contents) were determined
      experimentally. The sedimentation velocities were predicted under the various
      operational conditions and parameters, both of the broth (the alcohol
      concentration and cell content) and the sedimenter prototype (length, distance
      between the plates, and slope). The proposed model for the sedimentation velocity
      presented a good correlation with the experimental results of continuous
      sedimentation. These sedimenter prototypes were assembled and tested for
      efficiency of separation of yeast cell under conditions considered for interest
      for continuous alcoholic fermentation. A selective filter for the overflow
      composed of calcium alginate gel improved operation. A high operational
      stability, high separation efficiency (over 98%), and adequate settler residence
      times (about 20 min) were attained. The operational results permitted the
      operation of continuous alcoholic fermentation with cellular recycling effected
      exclusively by gravitational sedimentation, this characterizing a process of
      enormous industrial interest because of the operational simplicity and low
      operational and maintenance costs.

PMID- 18609562
TI  - Comparison of substrate utilization and growth kinetics between immobilized and
      suspended Pseudomonas cells.
AB  - A methodology is described for measurement if immobilized and suspended cell
      growth and substrate utilization kinetics parameters. Substrate utilization and
      growth kinetics were compared between immobilized and suspended cells for toluene
      degrading Pseudomonas strains K3-2 and 2,4-dichlorophenoxyacetic acid (2,4-D)
      degrading strain DBO131(pR0101), respectively. Kinetic parameters were estimated
      using nonlinear parameter estimation methods and compared between the immobilized
      and suspended Pseudomonas cells to determine the effect of immobilization on
      cellular growth and substrate utilization. Factors influencing the experimental
      design included calculated oxygen flux rates, primary carbon substrate flux
      rates, and shear stresses on the immobilize cell. Statistical interpretation of
      the cellular reaction rate parameters indicates that only the growth kinetics of
      the toluene system were significantly altered upon immobilization. Substrate
      utilization kinetics remained unchanged upon immobilization. The substrate growth
      associated half-saturation constant (K(g)) for the toluene system increased by 30
      fold and the maximum specific growth rate (micro(max)) decreased by 2-fold upon
      immobilization. Implication of these results for experimental determination of
      cellular kinetic parameters and for immobilization cell bioreactors design are
      discussed.

PMID- 18609563
TI  - Monitoring and modeling density-dependent growth of anchorage-dependent cells.
AB  - The density-dependent growth of Chinese hamster ovary (CHO) cells was monitored
      on-line by using an inverted microscope. A flow system was employed for cell
      cultivation so that nutrient concentration could be maintained and metabolic
      wastes were removed. With the help of video image analysis, local cells density
      could be accurately calculated and cell motility and exposed cell surface area
      could be estimated. A computer program which accounted for change of sell size
      and translocation of cells was developed to stimulate cell growth. The stimulated
      results of the population dynamics and the variations in cell size showed good
      agreement with our experimental observations, Cell motility and initial cell
      distribution on the substratum were found to have strong effect on cell growth.

PMID- 18609564
TI  - Are water-immiscibility and apolarity of the solvent relevant to enzyme
      efficiency?
AB  - The question of whether the solvent's water-immiscibility is relevant to
      enzymatic activity was addressed by assaying four different hydrolases (three
      lipases and one protease) in nine anhydrous solvents of similar hydrophobicities
      of which four were infinitely miscible with water and five were not. For no
      enzyme was a jump in activity observed upon a transition from water-miscible to
      water-immiscible solvent. The relevance of solvent apolarity to enzymatic
      efficiency was also examined. To this end, three groups of isomeric anhydrous
      solvents were selected where within each group of isomeric anhydrous solvents
      were selected where within each group one solvent was apolar (i.e., lacked a
      permanent dipole moment). For none of the four enzymes studied was activity
      significantly higher in apolar solvents than in their polar counterparts. Thus we
      conclude that often-cited solvent's immiscibility with water and apolarity by
      themselves are irrelevant to enzymatic activity.

PMID- 18609565
TI  - Correlation study of optimized voxel-based morphometry and (1)H MRS in patients
      with mesial temporal lobe epilepsy and hippocampal sclerosis.
AB  - PURPOSE: : To assess whether structural and metabolic brain abnormalities are
      correlated in MTLE/HS syndrome. METHODS: : Optimized voxel-based morphometry
      (VBM) of gray matter concentration (GMC) and gray matter volume (GMV) and proton
      magnetic resonance spectroscopy measurements from both-sided hippocampal and
      thalamic regions were performed in 20 MTLE/HS patients and 20 sex- and age
      matched healthy controls. The local GMC and GMV values were calculated in both
      the affected and unaffected hippocampi and ipsilateral and contralateral thalami
      in patients and healthy subjects, and these were compared. VBM variables and NAA,
      NAA/Cr and NAA/(Cr+Cho) values from the investigated brain regions were
      correlated. RESULTS: : (1) Analysis revealed significantly more extensive GMV
      reduction than GMC reduction in patients' affected hippocampus. In addition,
      significant GMV reduction was observed in the ipsilateral thalamus in MTLE/HS
      patients. (2) Significant decreases in all VBM and MRS variables were revealed in
      the affected hippocampus. Whilst practically normal GMC values were revealed in
      patients' both-sided thalamic regions, a significant decrease in local GMV and
      metabolic measurements were found in the patients' ipsilateral thalamus. (3)
      Pearson's correlations between structural and metabolic abnormalities were
      significant for the ipsilateral thalamus only. CONCLUSION: : Structural and
      metabolic abnormalities as detected by optimized voxel-based morphometry and (1)H
      MRS in hippocampal and thalamic regions are only partially correlated in MTLE/HS
      patients. It seems therefore reasonable that both methods reflect different
      aspects of brain pathology, which, at least to some degree, might be
      independently ongoing.

PMID- 18609567
TI  - Variation and modeling of the probability of plasmid loss as a function of growth
      rate of plasmid-bearing cells of Escherichia coli during continuous cultures.
AB  - A large number of models concerning cultures of genetically engineered bacteria
      have been described. Among them, some are specifically adapted to continuous
      cultures and lead to the determination of two variables: (i) the difference in
      the specific growth rates between plasmid-carrying cell and plasmid-free cells
      (deltamicro) and (ii) the frequency of plasmid loss by plasmid-containing cells
      (p(r)micro(+)). Until now, studies have been performed on the global expression
      p(r)micro(+) and deltamicro, whose value during continuous assays have been
      supposed approximately constant (mean value) and not on separate values of both
      terms p(r) and micro(+), respectively, probability of plasmid loss and specific
      growth rate of the plasmid-carrying cells. So far these studies do not allow
      examination of the relationship between these two last parameters. Experimental
      results were obtained with Escherichia coli C600 galk (GAPDH), a genetically
      engineered strain that synthetizes an elevated quantity of glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). From data obtained during continuous cultures,
      it is shown that during an assay, deltamicro, and p(r)micro(+) do not remain
      constant. An appropriate mathematical analysis of the expression of micro(-)
      (specific growth rate of the plasmid-free cells) and micro(+) has been built up.
      This allows the evaluation of the values of micro(+) and micro(-) during the
      continuous cultures carried out at different dilution rates. Values of p(r) have
      been calculated from these data. Indeed our results show that p(r) increases with
      micro(+). A modeling approach which allows correct simulation of this variation
      is also proposed. This model is derived from the Hill equation regarding
      cooperative binding of enzymic type reaction.

PMID- 18609569
TI  - Development of bacterial cytochrome P-450(cam) (cytochrome m) production.
AB  - Cytochrome P-450(cam) monooxygenase is an important bacterial redox enzyme system
      with potential commercial value for detoxifying trace hydrocarbon contaminants,
      catalyzing regiospecific hydroxylations, and amperometric biosensing. The present
      study was undertaken to increase productivity of this enzyme, which is induced in
      its host, pseudomonas putida PpG 786, by D(+)-camphor. Culture processes were
      studied in batch, fed-batch, and continuous modes to evaluate metabolic behavior
      and develop constitutive equations for specific rate of growth (micro), camphor
      utilization (q(p)). Fed-batch culture was characterized by an extended linear
      growth phase which is often encountered in hydrocarbon fermentations. Inhibition
      by the camphor solvent, dimethylformamide, was assessed. Production of the
      terminal protein of the p-450(cam) enzyme system, cytochrome m, was shown to
      depend on growth medium iron content in fed-batch culture and was increased by
      130% over previously protocols by eliminating iron deficiency. A continuous
      process that enables greater production rates was developed by using oxygen
      enrichment while simultaneously reducing gas throughput. Camphor and oxygen
      requirements were determined for fedbatch and continuous growth.

PMID- 18609568
TI  - Production of cellobiose by enzymatic hydrolysis: removal of beta-glucosidase
      from cellulase by affinity precipitation using chitosan.
AB  - Removal of beta-glucosidase (BG) from cellulase is essential to the enzymatic
      production of cellobiose from cellulose because of the high reactivity of BG with
      cellobiose to form glucose. Chitosan is a reversibly soluble-insoluble polymer
      depending on pH, and it has an affinity with the other components, endo-beta-1,4
      glucanase and cellobiohydrolase, or cellulase. The affinity precipitation
      technique using chitosan is an effective way to fractionate cellulase for the
      above purpose. Hydrolysis experiments of cellulose with the residual fractionated
      enzyme gave higher cellobiose contents in the soluble sugar products.

PMID- 18609570
TI  - Calculation of entropy change accompanying growth of Escherichia coli K-12 on
      succinic acid.
AB  - The DeltaSf of one unit carbon formula weight of Escherichia coli K-12 cells,
      when grown on succinic acid, was calculated to be -80.13 J/deg. This value could
      then be used to calculate the entropy change accompanying the anabolism and
      metabolism of succinic acid to be 30.82 J/deg and 32.40 J/mol deg, respectively.
      The entropy of one unit carbon formula weight of dried E. Coli K-12 cells is
      calculated to be 94.40 J/deg, which when divided by the mass of these cells
      becomes 3.90 J/g deg. The corresponding entropy of succinic acid is 2.77 J/g deg,
      making it apparent that the entropy per unit mass of the cells is greater than
      that of the substrate. It might be thought that because the cells appear to be so
      much more complex than the substrate, the cells should have a lesser entropy per
      unit mass than the substrate. That this does not appear to be true leads to the
      conclusion that the macromolecular organization (informational content?) of the
      cells contributes only in a very minor way to the total physical entropy of
      cells.

PMID- 18609571
TI  - Effect of dilution rate on growth, productivity, cell cycle and size, and shear
      sensitivity of a hybridoma cell in a continuous culture.
AB  - To study the effects of the growth rate of the hybridoma cell Mn12 on
      productivity, cell cycle, cell size, and shear sensitivity, six continuous
      cultures were run at dilution rate of 0.011, 0.021, 0.023, 0.030, 0.042, and
      0.058 h(-1). This particular hybridoma cell appeared to be unstable in continuous
      culture with respect to specific productivity, as a sudden drop occurred after
      about 30 generations in continuous culture, accompanied by the appearance of two
      populations with respect to the cytoplasmic lgG content. The specific
      productivity increased with increasing growth rate. The shear sensitivity of the
      cell, as measured in a small air-lift loop reactor, increased with increasing
      growth rate. The mean relative cell size, as determined with a flow cytometer,
      increased with increasing growth rates. Furthermore, the fraction of cells in the
      S phase increased, and the fraction of cells in the G1/G0 phase decreased with
      increasing growth rates.

PMID- 18609572
TI  - Toward a control of lignin and manganese peroxidases hypersecretion by
      Phanerochaete chrysosporium in agitated vessels: Evidence of the superiority of
      pneumatic bioreactors on mechanically agitated bioreactors.
AB  - Phanerochaete chrysosporium and cultivated both mechanically agitated and
      pneumatic bioreactors. In the pneumatic devices, the yields of lignin and
      manganese peroxidases as well as extracellular protein, were considerably
      increased as compared with mechanically agitated bioreactors. Lignin peroxidase
      and manganese peroxidase activities as high as 4500 U x L(-1) and 1812 U x L(-1)
      respectively, were produced in an airlift bioreactor. By using enzyme markers,
      the secretion pathway and the respiration were shown to be dramatically activated
      in pneumatic bioreactors. The general metabolism of the fungus, when cultivated
      in the conventional fermentors, is oriented toward the synthesis of biomass at
      the expense of the synthesis of peroxidases. The use of pneumatic devices for the
      production of extracellular peroxidases by P. chrysosporium, avoids shear effects
      due to turbine agitator in the conventional fermentors, and provides a good
      example for the production of shear-sensitive metabolites.

PMID- 18609573
TI  - Analysis of substrate protection of an immobilized glucose isomerase reactor.
AB  - The effect of substrate protection on enzyme deactivation was studied in a
      differential bed and a packed bed reactor using a commercial immobilized glucose
      isomerase (Swetase, Nagase Co.). Experimental data obtained from differential bed
      reactor were analyzed based on Briggs-Haldane kinetics in which enzyme
      deactivation accompanying the protection of substrate was considered. The
      deactivation constant of the enzyme-substrate complex was found to be about half
      of that of the free enzyme. The mathematical analysis describing the performance
      of a packed bed reactor under the considerations of the effects of substrate
      protection, diffusion resistance, and enzyme deactivation was studied. The system
      equations for the packed bed reactor were solved using an orthogonal collocation
      method. The presence of substrate protection and the diffusion effect within the
      enzyme particles resulted in an axial variation of effectiveness factor, eta(D),
      along the length of the packed bed. The axial distribution profile of eta(D) was
      found to be dependent on the operation temperature, Based on the effect of
      substrate protection, a better substrate feed policy could be theoretically found
      for promoting productivity in long-term operation.

PMID- 18609574
TI  - Effect of carbon dioxide concentration on the bioleaching of a pyrite
      arsenopyrite ore concentrate.
AB  - The effect of carbon dioxide concentration on the bacterial leaching of a pyrite
      arsenopyrite ore concentrate was studied in continuous-flow reactors. Steady
      state operation with two feed slurry densities, 6 wt% and 16 wt% solids, were
      tested for the effect of carbon dioxide concentration. Bacterial growth rates
      were estimated via the measurement of carbon dioxide consumption rates. Aqueous
      phase carbon dioxide concentrations in excess of 10 mg/L were found to be
      inhibitory to bacterial growth.

PMID- 18609575
TI  - Development of an enzyme membrane reactor for treatment of cyanide-containing
      wastewaters from the food industry.
AB  - Cyanidase, an immobilized enzyme preparation for hydrolyzing cyanide to ammonia
      and formate, was applied for the treatment of cyanide-containing waste waters
      from the food industry. Apricot seed extract was chosen as a model effluent. The
      enzymatic hydrolysis of pure amygdalin, the main cyanogenic glycoside in the
      extract, and the degradation of the cyanide formed was investigated and compared
      with the behavior of the real extract in a batch slurry reactor. A diffusional
      type, flat-membrane reactor with immobilized cyanidase was developed, where the
      enzyme is effectively protected from adverse effects of high molecular components
      contained in the extract. For monitoring continuous-membrane reactor operation, a
      new unsegmented ammonia measurement system was developed and applied. In
      continuous operation the cyanidase retained its original activity for more than
      400 hours on steam.

PMID- 18609576
TI  - Enzymatic activity under tangential flow conditions of photochemically grafted
      membranes containing immobilized catalase.
AB  - Catalase has been immobilized within sandwich membranes prepared by the
      photoinduced grafting of an epoxy-diacrylate prepolymer onto commercial
      asymmetric cellulose membranes. The enzymatic activity of the membrane composite
      of hydrogen peroxide decomposition has been studied in a recirculation apparatus
      under tangential flow conditions without ultrafiltration. The enzymatic membranes
      were exposed to very low mechanical stresses and showed a very good catalytic
      performance and durability. Initial reaction rates, measured at 25 degrees C as a
      function of both substrate concentration and enzyme amount immobilized per unit
      membrane surface, indicate that the mechanism of action of catalase is not
      altered after immobilization, although substrate diffusion through the original
      thin layer of membranes may become rate controlling.

PMID- 18609577
TI  - Intrinsic fermentation kinetics of lactose in acidogenic biofilms.
AB  - The intrinsic fermentation kinetics of lactose in acidogenic biofilms were
      investigated in situ in a continuous flow fermentor at 35 degrees C and pH 4.6.
      The external and internal mass transfer resistances to lactose molecules from
      bulk solution to inside the biofilms were experimentally minimized or eliminated
      in a thin biofilm and recycled medium. In a chemically defined culture medium,
      the immobilized acidogens converted lactose mainly to acetate and butyrate; the
      minor products included ethanol. propionate, lactate, and hydrogen. The
      utilization rate of lactose, as a function of lactose concentration in the
      fermentor, can be described by a Michaelis-Menten equation, as can the formation
      rates of acetate, butyrate, and ethanol. The production rates of propionate and
      lactate had a liner relationship with lactose concentration under the
      experimental conditions. The low pH (4.6) of culture medium could depress the
      formation of propionate, and intermediate which is most difficulty digested by
      acetogenic bacteria located in the second fermentor in a two-phase process.
      Production rate of acetate quickly reached a constant, and additional utilization
      of lactose produced more butyrate and other minor products.

PMID- 18609578
TI  - Reverse micelles in protein separation: the use of silica for the back-transfer
      process.
AB  - In order to use reverse micellar solutions successfully for the separation of
      proteins, good methods are needed to recover the biomolecules into an aqueous
      environment after solubilization into organic micellar media. Usually the
      recovery is accomplished by equilibrating the protein-loaded reverse micellar
      solution with a water phase containing an appropriate salt (back-transfer). In
      this article we describe an alternative "back extraction" procedure which is
      based on the addition of silica to the protein-containing reverse micellar
      solution. In this way, the water is stripped from the reverse micellar solution.
      [i.e., bis(2-ethylhexyl) sodium sulfosuccinate (AOT)/isooctane/water] and the
      proteins adsorb to the silica particles. The adsorption process is shown to be
      practically quantitative. The subsequent recovery of the proteins form the silica
      into an aqueous solution turns out to be most efficient at alkaline pH (pH 8); 60
      80 of the total protein (alpha-chymotrypsin or trypsin) could be recovered. The
      specific enzyme activity at the end of the whole cycle can be as high as 80-100%.
      The procedure is applied also for the back extraction from micellar solutions in
      which, instead of AOT, a biocompatible surfactant such as a synthetic short-chain
      lecithin was used. It is shown that the recovery of a alpha-chymotrypsin and
      trypsin is also achievable under these conditions in quite good yield and under
      good maintenance of the enzyme's catalytic activity.

PMID- 18609579
TI  - Fuzzy control of ethanol concentration its application to maximum glutathione
      production in yeast fed-batch culture.
AB  - A fuzzy logic controller (FLC) for the control of ethanol concentration was
      developed and utilized to realize the maximum production of glutathione (GSH) in
      yeast fedbatch culture. A conventional fuzzy controller, which uses the control
      error and its rate of change in the premise part of the linguistic rules, worked
      well when the initial error of ethanol concentration was small. However, when the
      initial error was large, controller overreaction resulted in an overshoot.An
      improved fuzzy controller was obtained to avoid controller overreaction by
      diagnostic determination of "glucose emergency states" (i.e., glucose
      accumulation or deficiency), and then appropriate emergency control action was
      obtained by the use of weight coefficients and modification of linguistic rules
      to decrease the overreaction of the controller when the fermentation was in the
      emergency state. The improved fuzzy controller was able to control a constant
      ethanol concentration under conditions of large initial error.The improved fuzzy
      control system was used in the GSH production phase of the optimal operation to
      indirectly control the specific growth rate mu to its critical value micro(c). In
      the GSH production phase of the fed-batch culture, the optimal solution was to
      control micro to micro(c) in order to maintain a maximum specific GSH production
      rate. The value of micro(c) also coincided with the critical specific growth rate
      at which no ethanol formation occurs. Therefore, the control of micro to micro(c)
      could be done indirectly by maintaining a constant ethanol concentration, that
      is, zero net ethanol formation, through proper manipulation of the glucose feed
      rate. Maximum production of GSH was realized using the developed FLC; maximum
      production was a consequence of the substrate feeding strategy and cysteine
      addition, and the FLC was a simple way to realize the strategy.

PMID- 18609581
TI  - Mathematical modeling of growth and alkaloid production in Claviceps purpurea
      batch fermentation.
AB  - An new systematic approach for describing Claviceps purpurea growth and ergot
      alkaloid production during batch fermentation is presented. The model is based on
      microbial life, as the main characteristic for microbial development during
      fermentation process. The aging process of the microorganism is represented by
      life function, defined in microbial life space. The life space is defined as a
      measure in which the observer follows the development of a biosystem through
      physiological and morphological changes of a microorganism. As a consequence of
      such approach the relativistic theory is recognized. To validate the model
      developed, a test on growth and alkaloid synthesis data from an industrial batch
      fermentation was performed.

PMID- 18609582
TI  - Biofiltration of methanol vapor.
AB  - Biofiltration of solvent and fuel vapors may offer a cost-effective way to comply
      with increasingly strict air emission standards. An important step in the
      development of this technology is to derive and validate mathematical models of
      the biofiltration process for predictive and scaleup calculations. For the study
      of methanol vapor biofiltration, an 8-membered bacterial consortium was obtained
      from methanol-exposed soil. The bacteria were immobilized on solid support and
      packed into a 5-cm-diameter, 60-cm-high column provided with appropriate
      flowmeters and sampling ports. The solid support was prepared by mixing two
      volumes of peat with three volumes of perlite particles (i.e., peat-perlite
      volume ratio 2:3). Two series of experiments were performed. In the first, the
      inlet methanol concentration was kept constant while the superficial air velocity
      was varied from run to run. In the second series, the air flow rate (velocity)
      was kept constant while the inlet methanol concentration was varied. The unit
      proved effective in removing methanol at rates up to 112.8 g h(-1) m(-3) packing.
      A mathematical model has been derived and validated. The model described and
      predicted experimental results closely. Both experimental data and model
      predictions suggest that the methanol biofiltration process was limited by oxygen
      diffusion and methanol degradation kinetics.

PMID- 18609583
TI  - Air slugs entrapped cross-flow filtration of bacterial suspensions.
AB  - A novel cross-flow technique for membrane filtration of bacterial cell
      suspensions was established. This is an air slugs entrapped cross-flow method in
      which air slugs were generated by introducing air into the cross-flow stream. As
      air slugs moved along with cross-flow, the disturbance of cell sublayer formation
      on membrane surface was enhanced. As a consequence, filtration flux was improved
      and stabilized. The effect of air slugs on improving filtration flux was more
      pronounced in filtering gram-negative Escherichia coli cell than gram-positive
      Brevibacterium flavum cell. Moreover, air slug was about 50% more effective on
      reducing filtration resistance using ultrafiltration (UF) membrane of 300,000
      molecular weight cutoff (MWCO) than microfiltration (MF) membrane of 0.2 microm.

PMID- 18609584
TI  - Catalytic and interfacial aspects of enzymatic polymer synthesis in reversed
      micellar systems.
AB  - The enzyme horseradish peroxidase, when encapsulated in reversed micelles, is
      capable of catalyzing the synthesis of phenolic and aromatic amine polymers. The
      synthesis of polyethylphenol is specifically considered in this article and is
      found to be extremely feasible in the micellar system. Polymer chain growth can
      be controlled to some degree by manipulating the ability of the solvent to
      sustain chain solubility; this is effectively done by adjusting the surfactant
      concentration. This results in a degree of control of polymer molecular weight.
      The synthesized polymer drops out of solution and can be easily recovered.

PMID- 18609585
TI  - Continuous measurement of microbial heat production in laboratory fermentors.
AB  - The possibility of continuously measuring the heat produced by microorganisms in
      an ordinary laboratory fermentor was studies. An inventory of the heat flows
      influencing the temperature of the culture was made. The magnitude and standard
      deviation in these heat flows were studied from theoretical and practical
      viewpoints. Calibration procedures were tested, and a model describing the heat
      flows in steady state and during dynamic conditions was made. Microbial heat
      production could be calculated accurately with the help of this model,
      appropriate temperature measurements, and equipment properties measured during
      the calibration procedures. It was found that the measurement of heat production
      could be done with an accuracy similar to that in the O(2) uptake measurement.

PMID- 18609586
TI  - High cell density cultivation of Pseudomonas oleovorans: growth and production of
      poly (3-hydroxyalkanoates) in two-liquid phase batch and fed-batch systems.
AB  - Pseudomonas oleovorans is able to accumulate poly(3-hydroxyalkanoates) (PHAs)
      under conditions of excess n-alkanes, which serve as sole energy and carbon
      source, and limitation of an essential nutrient such as ammonium. In this study
      we aimed at an efficient production of these PHAs by growing P. oleovorans to
      high cell densities in fed-batch cultures.To examine the efficiency of our
      reactor system, P. oleovorans was first grown in batch cultures using n-octane as
      growth substrate and ammonia water for pH regulation to prevent ammonium limiting
      conditions. When cell growth ceased due to oxygen limiting conditions, a maximum
      cell density of 27 g .L(-1) dry weight was obtained. When the growth temperature
      was decreased from the optimal temperature of 30 degrees -18 degrees C, cell
      growth continued to a final cell density of 35 g . L(-1) due to a lower oxygen
      demand of the cells at this lower incubation temperature.To quantify mass
      transfer rates in our reactor system, the volumetric oxygen transfer coefficient
      (k(L)a) was determined during growth of P. oleovorans on n-octane. Since the
      stirrer speed and airflow were increased during growth of the organism, the k(L)a
      also increased, reaching a constant value of 0.49 s(-1) at maximum airflow and
      stirrer speed of 2 L . min(-1) and 2500 rpm, respectively. This k(L)a value
      suggests that oxygen transfer is very efficient in our stirred tank reactor.Using
      these conditions of high oxygen transfer rates, PHA production by P. oleovorans
      in fed-batch cultures was studied. The cells were first grown batchwise to a
      density of 6 g . L(-1), after which a nutrient feed, consisting of
      (NH(4))(2)SO(4) and MgSO(4), was started. The limiting nutrient ammonium was
      added at a constant rate of 0.23 g NH(4) (+) per hour, and when after 38 h the
      feed was stopped, a biomass concentration of 37.1 g . L(-1) was obtained. The
      Cellular PHA content was 33% (w/w), which is equal to a final PHA yield of 12.1 g
      . L(-1) and an overall PHA productivity of 0.25 g PHA produced per liter medium
      per hour.

PMID- 18609587
TI  - Enhancement of recombinant protein synthesis and stability via coordinated amino
      acid addition.
AB  - In this work, effective feeding schemes that would minimize stress responses to
      cloned-protein overexpression are investigated. The cloned-protein
      (chloramphenicolacetyl-transferase, CAT) contains a high aromatic amino acid
      content, most notably a high phenylalanine content. Experiments performed on
      Escherichia coli RR1 [pBR329] (constitutive promoter) and E. coli JM105 [pSH101]
      (inducible promoter) demonstrated that phenylalanine addition increases the rate
      of synthesis and yield of CAT. A previous study correlating inducer strength with
      CAT expression in E. coli JM105 [pSH101] indicated that the highest expression
      rate was accompanied by the highest apparent rate of protein degradation. In this
      work, the combined addition of isopropyl-beta-D-thiogalactopyranoside (IPTG) and
      phenylalanine at intermediate levels resulted in substantial increase of CAT
      synthesis and partial reduction of protein degradation. Furthermore, transmission
      electron micrographs verified the absence of inclusion bodies, which, along with
      proteases, were suspected to reduce protein activity. The research demonstrates
      that significant enhancement in production and stability of heterologous proteins
      is possible by designing feeding strategies that incorporate knowledge of the
      interaction between primary cellular metabolism and foreign protein expression.

PMID- 18609588
TI  - Dramatic enhancement of enzymatic activity in organic solvents by lyoprotectants.
AB  - When seven different hydrolytic enzymes (four proteases and three lipases) were
      lyophilized from aqueous solution containing a ligand, N-Ac-L-Phe-NH(2), their
      catalytic activity in anhydrous solvents was far greater (one to two orders of
      magnitude) than that of the enzymes lyophilized without the ligand. This ligand
      induced activation was expressed regardless of whether the substrate employed in
      organic solvents structurally resembled the ligand. Furthermore, nonligand
      lyoprotectants [sorbitol, other sugars, and poly(ethylene glycol)] also
      dramatically enhanced enzymatic activity in anhydrous solvents when present in
      enzyme aqueous solution prior to lyophilization. The effects of the ligand and of
      the lyoprotectants were nonadditive, suggesting the same mechanism of action.
      Excipient activated and nonactivated enzymes exhibited identical activities in
      water. Also, addition of the excipients directly to suspensions of nonactivated
      enzymes in organic solvents had no appreciable effect on catalytic activity.
      These observations indicate that the mechanism of the excipient-induced
      activation is based on the ability of the excipients to alleviate reversible
      denaturation of enzymes upon lyophilization. Activity enhancement induced by the
      excipients is displayed even after their removal by washing enzymes with
      anhydrous solvents. Subtilisin Carlsberg, lyophilized with sorbitol, was found to
      be a much more efficient practical catalyst than its "regular" counterpart.

PMID- 18609589
TI  - Dynamics of phenol degradation by Pseudomonas putida.
AB  - Pure cultures of Pseudomonas putida (ATCC 17484) were grown in continuous culture
      on phenol at dilution rates of 0.074-0.085 h(-1) and subjected to step increases
      in phenol feed concentration. Three distinct patterns of dynamic response were
      obtained depending on the size of the step change used: low level, moderate
      level, or high level. During low level responses no accumulations of phenol or
      non-phenol, non-glucose-dissolved organic carbon, DOC(NGP), were observed.
      Moderate level responses were characterized by the transient accumulation of
      DOC(NGP) with a significant delay prior to phenol leakage. High level responses
      demonstrated a rapid onset of phenol leakage and no apparent accumulations of
      DOC(NGP). The addition of phenol to a continuous culture of the same organism on
      glucose did not result in transient DOC(NGP) accumulations, although transient
      phenol levels exceeded 90 mg l(-1). These results were consistent with
      intermediate metabolite production during phenol step tests coupled with
      substrate-inhibited phenol uptake and suggested that traditional kinetic models
      based on the Haldane equation may be inadequate for describing the dynamics of
      phenol degrading systems.

PMID- 18609590
TI  - Production of indole alkaloids by selected hairy root lines of Catharanthus
      roseus.
AB  - Hairy root cultures of Catharanthus roseus were established by infection of
      seedlings with Agrobacterium rhizogenes 15834. Approximately 150 transformants
      from four different. C. roseus cultivars were screened for desirable traits in
      growth and indole alkaloid production. Five hairy root clones grew well in liquid
      culture with doubling times similar to those reported for cell suspensions. Fast
      growing clones had similar morphologies, characterized by thin, straight, and
      regular branches with thin tips. The levels of key alkaloids, ajmalicine,
      serpentine, and catharanthine, in these five clones, also compared well with
      literature data from cell suspensions, yet HPLC and GC-MS data indicate the
      presence of vindoline in two clones at levels over three orders of magnitude
      greater than the minute amounts reported in cell culture. These results suggest
      that further optimization may result in hairy roots as a potential source of
      vindoline and catharanthine, the two monomers necessary to synthesize that
      antineoplastic drug, vinblastine.

PMID- 18609591
TI  - Dynamics of transcriptional and translational processes in hepatocytes cultured
      in a collagen sandwich.
AB  - A mathematical model which simulates the dynamic behavior of the hepatocytes
      cultured in a collagen sandwich is presented. Using several independently
      determined experimental parameters (e.g., albumin gene nuclear runoff activity,
      the level of albumin mRNA, and the albumin secretion rate), we have used this
      model to calculate the in vivo albumin gene transcriptional rate (0.27 molecules
      per second per hepatocyte), the half-life of albumin mRNA (3.3 days) in cultured
      hepatocytes, and the albumin polypeptide elongation rate (10 amino acids per
      second). In addition, the characteristic time constants for the transient
      increases in transcription (5 days) and in translation (10 days) were also
      obtained. These best fit parameters were used to predict the rate of albumin
      secretion in rescued hepatocytes.

PMID- 18609592
TI  - Optimization of fed-batch fermentors by iterative dynamic programming.
AB  - By using penalty functions to handle state constraints, iterative dynamic
      programming can be used in a straightforward manner for the optimization of fed
      batch fermentors. No computational difficulties were encountered and better
      results are obtained than previously reported in the literature for a fed-batch
      fermentor for biosynthesis of penicillin.

PMID- 18609593
TI  - Brief communication: state of preservation of tissues from ancient human remains
      found in a glacier in Canada.
AB  - Ancient remains preserved in glaciers present a unique opportunity for us to
      advance our knowledge of human origins, diversity, and health, a central focus of
      anthropological studies. Cellular components of hard and soft tissue from frozen
      human remains dated between 1670 to 1850 cal AD recovered from a glacier in
      Canada were studied. Despite the expected ice crystal damage in some samples,
      regions of recognizable structure and ultrastructure were observed. We found that
      the state of preservation was tissue specific and that in some tissues the
      organelles were better preserved than in others. Skeletal, connective, nervous,
      and epithelial tissues were recognizable in some of the samples. DNA had been
      previously extracted from these remains and this study illustrates that the
      ability to successfully extract DNA may correlate with good preservation of
      histology.

PMID- 18609595
TI  - Action of lipolytical enzymes in biphasic organic-aqueous systems: dynamics of
      the irreversible Michaelis-Menten reaction.
AB  - Through simple model analysis, the mass action kinetic model for lipolytic
      enzymes in biphasic aqueous-organic systems can be simplified using the quasi
      steady state assumption (or the quasi-equilibrium state assumption) for the
      adsorbed enzyme E* or the enzyme-substrate complex E*S. Some parameter
      combinations leading to the above assumptions are derived confirmed by full
      numerical integration of the whole enzymatic process. The results may be
      classified into three categories: (1) the quasi-equilibrium state assumption for
      E*, (2) the quasi-steady state assumption for E*, and (3) the quasi-steady state
      assumption for E*S. Further simplification for both E* and E*S is also discussed.

PMID- 18609596
TI  - Dissolution of sulphur particles by Thiobacillus ferrooxidans: substrate for
      unattached cells.
AB  - The growth of Thiobacillus ferrooxidans on sulphur is known to proceed through
      the attachment of cells to the sulphur particles. Experiments, However, show that
      the cells in the liquid phase, which are not attached to the sulphur particles,
      also grow. It has been shown through the use of a two-compartment membrane
      reactor that this increase is partially due to the release of ions, corresponding
      to partially oxidized of sulphur, into the solution by the attached cells. The
      main soluble ion has been found to the thiosulphate, but traces of sulphite have
      also been detected.

PMID- 18609597
TI  - Factors affecting the performance of crossflow filtration of yeast cell
      suspension.
AB  - Factors affecting the performance of crossflow filtration were investigated with
      a thin-channel module and yeast cells. In crossflow filtration of Saccharomyces
      cerevisiae cells cultivated with YPD medium (Yeast extract, polypeptone, and
      dextrose) and suspended in saline, a steady state was attained within several
      minutes when the cell concentration was low and the circulation flow rate was
      high. The steady-state flux and the change in flux during the initial unsteady
      state were explained well by conventional filtration theory, with the amount of
      cake deposited and the mean specific resistance to the cake measured in a dead
      end filtration apparatus used in calculation. When the circulation flow rate was
      lower than a critical value, a part of the channel of the crossflow filtration
      module was plugged with cell cake, and thus the steady-state flux was low. In
      crossflow filtration of suspensions of commercially available baker's yeast, the
      flux gradually decreased, and the flux after 8 h of filtration was lower than the
      value calculated by filtration theory. Fine particles contaminating the baker's
      yeast was responsible for the decrease. A similar phenomenon was responsible for
      the decrease. A similar phenomenon was observed in crossflow filtration of a
      broth of S. cerevisiae cells cultivated in molasses medium, which also contains
      such particles, had no effect of the permeation flux during crossflow filtration.

PMID- 18609598
TI  - Criteria to assess when biodegradation is kinetically limited by intraparticle
      diffusion and sorption.
AB  - To determine when intraparticle diffusion and sorption can influence the rate of
      biodegradation, we consider the biodegradation of a pollutant diffusing into or
      out of porous aggregates suspended in a liquid medium, where the reactant is
      metabolized by bacteria. The pollutant that diffuses into the aggregates obeys a
      sorption-desorption equilibrium isotherm at sites on inner pore surfaces. The
      governing partial differential equations for the transient process describe (a)
      the local equilibrium sorption-desorption and the diffusion of the pollutant in
      the porous aggregate, (b) the mass transfer of the pollutant from the external
      surface of the spherical aggregates to the reaction medium, and (c) the
      biodegradation of the pollutant in the external medium. Illustrative calculations
      are presented for a linear sorption calculations are presented for a linear
      sorption isotherm and first-order biodegradation kinetics. A dimensionless group,
      comprised of the diffusion coefficient, biodegradation rate coefficient,
      aggregate characteristics length (radius), and adsorption capacity, serves as a
      criterion for determining when intraparticle diffusion can be ignored. The model
      provides a realistic description of experimental data for biodegradation of a
      pollutant subject to intraparticle diffusion and sorption.

PMID- 18609599
TI  - Metabolic flux distributions in Corynebacterium glutamicum during growth and
      lysine overproduction.
AB  - The two main contributions of this are the solidification of Corynebacterium
      glutamicum biochemistry guided by bioreaction network analysis, and the
      determination of bansal metabolic flux distributions during growth and lysine
      synthesis. Employed methodology makes use of stoichiometrically based mass
      balances to determine flux distributions in the C. glutamicum metabolic network.
      Presented are a brief description of the methodology, a through literature review
      of glutamic acid bacteria biochemistry, and specific results obtained through a
      combination of fermentation studies and analysis-directed intracellular assays.
      The latter include the findings of the lack of activity of glyoxylate shunt, and
      that phosphoenolpyruvate carboxylase (PPC) is the only anaplerotic reaction
      expressed in C. glutamicum cultivated on glucose minimal media. Network
      simplifications afforded by the above findings facilitated the determination of
      metabolic flux distributions under a variety of culture conditions and led to the
      following conclusions. Both the pentose phosphate pathway and PPC support fluxes
      during growth and lysine overproduction branch point does not appear to limit
      lysine synthesis.

PMID- 18609600
TI  - Comparison of glucose fermentation by suspended and gel-entrapped yeast cells: An
      in vivo nuclear magnetic resonance study.
AB  - Phosphorus-31 nuclear magnetic resonance ((31)P NMR) was used to compare the
      anaerobic metabolism of glucose by suspended and gel-entrapped Saccharomyces
      bayanus cells. The fermentation of glucose was carried out in a reaction system
      with continuous circulation through the NMR sample tube. The intracellular pH and
      the levels of some phosphorylated compounds were the levels of some
      phosphorylated compounds were noninvasively monitored by (31)P NMR while glucose,
      fermentation products, and biomass were determined by analytic techniques
      comparisons showed that no significant differences are observed in the relative
      concentrations in the spectra, but distinct profiles for the variation of both
      intracellular and extracellular pH are found. The internal pH of immobilized
      cells is maintained at a constant value throughout the fermentation as opposed to
      freely suspended cells for which a steady decrease in the internal pH occurs. A
      faster and stronger acidification is also observed in the external medium of the
      assays with suspended cells. Furthermore, higher yields for ethanol and biomass
      production and lower yields of fermentation by-products are obtained with
      immobilized cells. It is concluded that the higher intracellular pH achieved in
      the presence of the gel matrix had a regulatory effect on the metabolism which
      favored the ethanol production pathway.

PMID- 18609601
TI  - Enhancement effect of polyethylene glycol on enzymatic synthesis of cephalexin.
AB  - In an enzymatic synthesis of cephalexin (CEX) using an acylase from Xanthomonas
      citri, the effect of polyethylene glycol (PEG) on the synthetic reaction of 7
      amino-3-deacetoxycephalosporanic acid (7-ADCA) and D-alpha-phenyl-glycine methyl
      ester (PGM) to CEX was investigated. The addition of PEG (MW 300-20,000)
      increased the yield significantly. This yield enhancement effect tended to
      increase with the increasing molecular weight of PEG. Addition of PEG to the
      reaction system did not affect both the CEX and PGM hydrolytic reactions. The PEG
      added to the reaction medium used in these experiments did not depress the water
      activity significantly, and the product yield improvement could not be explained
      by the activity alone. The PEG stabilized the enzyme activity to some extent, but
      this stabilizing effect was only partially attributable to the yield enhancement
      of CEX. The enhancing effect of PEG on the synthetic yield increased with the
      increasing PEG molecular weight or the length of the poly(oxy-1,2-ethanediyl)
      chain, which increases the hydrophobicity of PEG. This finding consequently has
      led to the conclusion that the PEG structure renders the affinity between enzyme
      and 7-ADCA, which is a hydrophobic substrate. The microenvironmental
      hydrophobicity of PEG and its interaction with the hydrophobic substrate was
      found to be the main reason for the improvement of the CEX yield. In fact, the
      Michaelis-Menten kinetic constant for 7-ADCA, K(7-ADCA) in the presence of PEG
      was smaller than that in the control system (without PEG addition).

PMID- 18609602
TI  - Monitoring glutamine in animal cell cultures using a chemiluminescence fiber
      optic biosensor.
AB  - Together with flow injection analysis (FIA), a chemiluminescence (CL) fiber optic
      biosensor system has been developed for determining glutamine in animal cell
      cultures. Glutaminase (GAH) and glutamate oxidase (GLO) were onto separate porous
      aminopropyl glass beads via glutaraldehyde activation and packed to form an
      enzyme column. These two enzymes acted in sequence on glutamine to produce
      hydrogen peroxide, which was then reacted with luminol in the presence of
      ferricyanide to produce a light signal. An anion exchanger was introduced on-line
      to eliminate interfering endogenous glutamate in view of its negative charge at
      pH above 3.22 (isoelectric pH). Among several resins tested, the acetate form was
      most effective, and this type of ion exchanger also effectively adsorbed uric
      acid, acetaminophen, and aspartic acid.There was an excellent linear relationship
      between the CL response and standard glutamine concentration in the range 1 to
      100 muM. A complete analysis could be performed in 2 min, including sampling and
      washing with a good reproducibility (+/- 4.4%). Both the bi-enzymic and ion
      exchange columns were useful for at least 500 analyses when the biosensor system
      was applied for the glutamine determination in murine hybridoma cell cultures and
      insect cell cultures. The values obtained compared well with those of HPLC, thus
      validating the applicability of the CL fiber optic system.

PMID- 18609603
TI  - Effect of oxygen fluctuations on recombinant Escherichia coli fermentation.
AB  - Escherichia coli DH5alpha, carrying the pUC19 plasmid for the lacZ fragment of
      beta-galactosidase and ampicillin resistance, was grown in a batch fermentor
      under conditions of fluctuating oxygen supply. A Monte Carlo method was used to
      control the on/off supply of air to simulate circulation of cells in a large
      fermentor. Rapid changes in oxygen supply reduced the rates of oxygen uptake the
      carbon dioxide release and prolonged the active second growth phase in batch
      culture, compared to growth with continuous aeration. Amplification of the
      plasmid was observed during the stationary phase when air supplied continuously,
      but not during the Monte Carlo experiments.

PMID- 18609604
TI  - Mechanism of microbial flotation using Thiobacillus ferrooxidans for pyrite
      suppression.
AB  - Microbial desulfurization might be developed as a new process for the removal of
      pyrite sulfur from coal sluries such as coal-water mixture (CWM). An application
      of iron-oxidizing bacterium Thiobacillus ferrooxidans to flotation would shorten
      the periods of the microbial removal of pyrite from some weeks by leaching
      methods to a few minutes. The floatability of pyrite in flotation was mainly
      reduced by T. ferrooxidans itself rather than by other microbial substances in
      bacterial culture as additive of flotation liquor. Floatability was suppressed
      within a few seconds by bacterial contact. The suppression was proportional to
      increasing the number of cells observed between bacterial adhesion and the
      suppression of floatability. If 25% of the total pyrite surface area covered with
      the bacteria, pyrite floatability would be completely depressed. Bacteria that
      lost their iron-oxidizing activities by sodium cyanide treatment were also able
      to adhere to pyrite and reduced pyrite floatability as much as normal bacteria
      did. Thiobacillus ferrooxidans ATCC 23270, T-1, 9, and 11, which had different
      iron-oxidizing abilities, suppressed floatability to similar-levels. The
      oxidizing ability of bacteria did not influence the suppressing effect. These
      results showed the mechanism of the suppression of pyrite floatability by
      bacteria. Quick bacterial adhesion to pyrite induced floatability suppression by
      changing the surface property from hydrophobic. The quick adhesion of the
      bacterium was the novel function which worked to change the surface property of
      pyrite to remove it from coal.

PMID- 18609605
TI  - Cell retention culture with an internal filter module: continuous ethanol
      fermentation.
AB  - A new internal filter feedback system with a stainless steel filter was
      introduced and its application for continuous ethanol fermentation was
      investigated. The filter performance was highly influenced by agitation speed and
      yeast concentration. Retention coefficient with a filter of 2 mum pore size was
      found more than 97.5%, and the filter was suitable for yeast separation. Maximum
      yeast concentration was 157 g/L and the best operable cell concentration was
      between 90 and 150 g/L. Which was similar to that obtained in the external
      membrane cell recycle culture. The cell concentration in the fermentor was
      maintained by manipulation of dilution rate and bleed ratio with the growth rate.
      The internal filter feedback system was successfully operated for more than 10
      days. This study shows that the internal filter feedback system with a stainless
      steel filter can be used high-density cell culture and ethanol fermentation.
      Furthermore, it can be scaled up more easily than the external cell recycle
      system.

PMID- 18609610
TI  - A comparison of oxygenation methods fro high-density perfusion culture of animal
      cells.
AB  - A perfusion culture system was developed to investigate the oxygenation of high
      density hybridoma cell cultures. The culture system was composed of a stirred
      tank bioreactor and an external microfiltration hollow fiber cartridge for medium
      perfusion. Cell growth and antibody production were examined with large bubble (
      approximately 5 mm in diameter), micron-sized bubble ( approximately 80 mum in
      diameter), and silicone tubing oxygenation techniques. Comparable cell growth and
      monoclonal antibody (MAb) production were found for both the micron-sized and
      large oxygenation methods, provided that large bubbles were enriched with pure
      oxygen. Relatively low cell growth and MAb production were attained with the
      bubble-free silicone tubing oxygenation. It is concluded that direct bubble
      oxygenation can be applied successfully in high-density animal cell cultures,
      provided that the culture medium is supplemented with Pluronic F-68. The
      accumulation of ammonia in the culture medium rather than oxygen limitation was
      found to be one of the possible problems that eventually inhibited cell growth.
      This and the fouling of the filtration cartridge during long-term cultivation
      were found to be more problematic than simple bubble oxygenation of high-density
      cell culture. The micron-sized bubble oxygenation method is highly recommended
      for high-density animal cell cultures, provided that Pluronic F-68 is
      supplemented into the culture medium.

PMID- 18609611
TI  - Phenol removal from waste gases with a biological filter by Pseudomonas putida.
AB  - The purpose of this study is to investigate the feasibility of biologically
      removing phenol from waste gases by means of a biofilter using a Pseudomonas
      putida strain. Two series of both batch and continuous tests have been performed
      in order to ascertain the microbial degradation of phenol. For the preliminary
      batch tests, carried out in order to test the effective feasibility of the
      process and to investigate their kinetic behavior, two different microbial
      cultures belonging to the Pseudomonas genus have been employed, a heterogeneous
      culture and a pure strain of P. putida. The results of these comparative
      investigation showed that the pure culture is more efficient than the mixed one,
      even when the latter has undergone three successive acclimatization tests. The
      continuous experiments have been conducted during a period of about 1 year in a
      laboratory-scale column, packed with a mixture of peat and glass beads, and
      utilizing the pure culture of P. putida as microflora and varying the inlet
      phenol concentration from 50 up to 2000 mg m(-3). The results obtained show that
      high degrees of conversion can be obtained (0.93/0.996) operating at a residence
      time of 54 s.

PMID- 18609612
TI  - Instability caused by high strength of cheese whey in a UASB reactor.
AB  - The anaerobic digestion of cheese whey was studied in a UASB reactor. The
      profiles of the reactor, i.e., the distributions of the substrate concentration
      and pH under different operating conditions were developed. From the
      concentrations of substrates measured at various levels above the bottom of the
      reactor, two reaction stages, namely acidogenesis and methanogenesis, were
      distinguished. The instability caused by high influent concentration was
      interpreted as the accumulation of VFAs in the acidogenic stage beyond the
      assimilative capacity of the methanogenic stage. A range of stable operating
      conditions was predicted from the results of the profile measurements. The
      optimal influent concentration was found to be between 25 and 30 g COD/L at an
      HRT of 5 days for system stability. Other options fro stability control were
      discussed.

PMID- 18609613
TI  - A simple genetically structured model of trp repressor-operator interactions.
AB  - A genetically structured mathematical model of the trp operon based on known
      molecular interactions of aporepressor, corepressor, and inducer is proposed. The
      model simulates, both qualitatively and quantitatively, the influence of these
      regulatory species on the extent of repression and expression of cloned gene
      products. It shows that at low aporepressor concentration, full repression is not
      possible even with high tryptophan levels, resulting in leaky expression.
      Calculations based on the model enabled predictions of optimum levels of
      aporepressor and tryptophan for effective repression and, concurrently, the beta
      indoleacrylic acid concentrations required for induction for both low and high
      plasmid copy number clones. Using the model we attempted to provide explanations
      for seemingly anomalous and sometimes contradictory observations by researchers
      when working with the trp promoter.

PMID- 18609614
TI  - A simple morphologically structured model describing the growth of filamentous
      microorganisms.
AB  - Based on the reported mechanisms for filamentous growth, a simple morphologically
      structured growth model is set up. The model may describe the growth of
      filamentous microorganisms both on a solid medium and in a submerged culture. For
      description of a submerged culture the model is combined with a simple population
      model, which is derived from a balance for the distribution function for the
      hyphal elements. The model is compared with experimental data for three species
      of filamentous microorganisms: Geotrichum candidum, Streptomyces hygroscopicus,
      and Penicillium chrysogenum.

PMID- 18609615
TI  - A statistical analysis of the effect of substrate utilization and shear stress on
      the kinetics of biofilm detachment.
AB  - One of the least understood processes affecting biofilm accumulation is
      detachment. Detachment is the removal of cells and cell products from an
      established biofilm and subsequent entrainment in the bulk liquid. The goal of
      this research was to determine the effects of shear stress and substrate loading
      rate on the rate of biofilm detachment. Monopopulation Pseudomonas aeruginosa and
      undefined mixed population biofilms were grown on glucose in a RotoTorque biofilm
      reactor. Three levels of shear stress and substrate loading rate were used to
      determine their effects on the rate of detachment. Suspended cell concentrations
      were monitored to determine detachment rates, while other variables were measured
      to determine their influence on the detachment rate. Results indicate that
      detachment rate is directly related to biofilm growth rate and that factors which
      limit growth rate will also limit detachment rate. No significant influence of
      shear on detachment rate was observed.A new kinetic expression that incorporates
      substrate utilization rate, yield, and biofilm thickness was compared to
      published detachment expressions and gives a better correlation of data obtained
      both in this research and from previous research projects, for both mono- and
      mixed-population biofilms.

PMID- 18609616
TI  - Diffusion of lactose in acidogenic biofilms.
AB  - Effective diffusivity of lactose in active acidogenic biofilms was measured at 35
      degrees C and pH 4.6 with a specially designed diffusion cell. The diffusion cell
      was designed and operated in such a way that the lactose concentrations on the
      surface and at the center of a living bacterial aggregate could be measured at
      steady state. As a model parameter in a widely accepted reaction-diffusion
      equation which describes lactose distribution in living biofilms, the effective
      diffusivity of lactose in the biofilms was found to be about 65% of the lactose
      diffusivity in free solutions. It was experimentally determined that the active
      biofilms had about 66% void volume made up of channels through which the lactose
      molecules were transported into the bacterial aggregates. Therefore, the decrease
      in lactose diffusivity was mainly caused by the biofilm's solid biomass fraction
      rather than the tortuosity of the channels.

PMID- 18609617
TI  - Rheological properties of mammalian cell culture suspensions: Hybridoma and HeLa
      cell lines.
AB  - Data on viscous (eta') and elastic (eta'') components of the complex viscosity
      versus oscillatory angular frequency (0.01 to 4.0 rad/s) with increasing strains
      were obtained for hybridoma cell (62'D3) and HeLa cell (S3) suspensions in PBS at
      0.9 (mL/mL) cell volume fraction using a Weissenberg rheogoniometer equipped with
      two parallel plate geometry at ambient temperature. Both cell suspensions
      exhibited shear thinning behavior. From the measured viscoelastic properties, the
      yield stress was calculated. Hybridoma cell suspension (15 microm as the mean
      diameter of cells) showed the yield stress at 550 dyne/cm(2) that was 1.8 times
      higher than the value of HeLa cell suspension (22 microm mean diameter) as
      measured at the oscillatory angular frequency, 4.0 rad/s. The apparent
      viscosities of HeLa cell suspension at four concentrations and varying steady
      shear rate were also determined using the Brookfield rotational viscometer. The
      yield stress to steady shear test was about 130 dyne/cm(2) for HeLa cell
      suspension at 0.9 (mL/mL) cell volume fraction. The apparent viscosity was in the
      range about 1 approximately 1000 Poise depending on the cell concentration and
      shear rate applied. A modified semiempirical Mooney equation, eta = eta(0) exp[K
      gamma(.)(-beta)phi(c)(1 - K'' sigmaphi(c) /D)] was derived based on the cell
      concentration, the cell morphology, and the steady shear rate. The beta, shear
      rate index, was estimated as 0.159 in the range of shear rate, 0.16 to 22.1 s(
      1), for the cell volume fractions from 0.6 to 0.9 (mL/mL). In this study, the
      methods of determining the shear sensitivity and the viscous and the elastic
      components of mammalian cell suspensions are described under the steady shear
      field.

PMID- 18609618
TI  - Diffusivity of Cu(2+) in calcium alginate gel beads.
AB  - A linear absorption model (LAM) is used to describe the process of metal binding
      to spherically shaped biopolymers particles. The LAM was solved using a numerical
      algorithm which calculates diffusivities of metal ion in biopolymer gels. It
      assumes attainment of rapid metal-biopolymer binding equilibrium accompanied by
      rate limiting diffusion of the metal ions through the gel. The model was tested
      using batch experiments in which copper (Cu(2+)) binding with calcium alginate
      beads was investigated. Biopolymer density in the beads was varied between 2% and
      5%. The diffusion coefficient of Cu(2+) calculated from the LAM ranged from 1.19
      x 10(-9) to 1.48 x 10(-9) m(2) s(-1) (average 1.31 +/- 0.21 x 10(-9) m(2) s(-1)),
      independent of biopolymer density. The LAM has theoretical advantages over the
      shrinking core model (shell progressive model). The latter calculated an
      unreasonable exponential increase in the diffusion coefficient as density of
      alginate polymer in the bead increased.

PMID- 18609620
TI  - An ultrafiltration membrane bioreactor for the lipolysis of olive oil in reversed
      micellar media.
AB  - The enzymatic hydrolysis of olive oil using Chromobacterium viscosum lipase B
      encapsulated in reversed micelles of dioctyl sodium sulfosuccinate (AOT) in
      isooctane was investigated in an ultrafiltration ceramic membrane reactor of
      tubular type, operating in a batch mode. Water concentration was found to be a
      critical parameter in the enzyme kinetics and hydrolysis yield of the reaction.
      The size of micelles, recirculation rate, and substrate concentration were found
      to be the major factors affecting the separation process. A correlation that
      enables the prediction of final conversion degrees in this bioreactor from the
      initial reaction conditions was established.

PMID- 18609621
TI  - A structured model describing carbon and phosphate limited growth of Catharanthus
      roseus plant cell suspensions in batch and chemostat culture.
AB  - The growth of plant cell suspension cultures of Catharanthus roseus in batch
      fermentors was studied at different initial phosphate levels of the medium. On
      the basis of the observations and existing knowledge with respect to phosphate
      metabolism in cultured C. roseus cells, a structured mathematical model was
      developed for the description of the kinetics of growth and intracellular
      accumulation of glucose and phosphate, as a function of glucose and phosphate
      supply. It was shown that the model offers not only good description of the
      growth of the cells in batch culture at different initial phosphate levels, but
      also provided a satisfactory description of the growth in glucose limited
      chemostats.

PMID- 18609622
TI  - Recombinant trypsin production in high cell density fed-batch cultures in
      Escherichia coli.
AB  - Fed-batch techniques were employed to obtain high cell density cultures (92-100 g
      DCW/L) of Escherichia coli strain X90 producing a recombinant serine protease,
      rat anionic trypsin, secreted to the periplasm. The specific growth rate was
      controlled to minimize growth-inhibiting acetate formation by utilizing an
      exponential feeding profile determined from mass balance equation. The volumetric
      yield of recombinant rat anionic trypsin was 56 mg/L, and the final cell density
      was 92 g DCW/L when the culture was induced in the late logarithmic phase.
      However, when the culture was induced in the early logarithmic phase, the
      volumetric yield was 13 mg/L and the final cell density was 14 g DCW/L. Thus, the
      induction timing is shown to have a significant effect on the final cell density
      as well as the overall volumetric yield of the recombinant protease.

PMID- 18609623
TI  - A simulation model for the continuous production of acetoin and butanediol using
      Bacillus subtilis with integrated pervaporation separation.
AB  - The potential for producing acetoin and butanediol with a Bacillus subtilis
      strain was investigated with continuous culture using molasses as carbon
      substrate. The steady-state results were influenced by both oxygen and
      undetermined limiting compounds. Employing the known metabolic pathways, four
      overall stoichiometry relations were used with an energetic assumption on the
      energy requirements for biomass formation to establish a linear relations were
      used with an energetic assumption on the energy requirements for biomass
      formation to establish a linear relation between the overall rates, whose
      parameters were determined by linear regression. This provided a relationship for
      the product formation rate. The chemostat culture data were described with a
      growth kinetics model, which included limitation by molasses and oxygen as well
      as diauxic effects and product inhibition. The biokinetics model was combined
      with an experimentally verified model for the membrane Pervaporation. From this
      combined model were determined the influence of the membrane characteristics
      (enrichment factors and membrane area) and the dilution rate on the performance
      of the integrated process. Simulations revealed that an increase of the
      enrichment factor, possible by membrane improvement, would have counteracting
      influences, owing to decreased product inhibition but with lower biomass
      concentration.

PMID- 18609624
TI  - Enhancement of cloned gene product synthesis via autoselection in recombinant
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae autoselection strains with mutations in the ura3, fur1,
      and urid-k genes have been obtained through a sequential isolation procedure.
      This autoselection system is an extension of one described by Loison et al. The
      mutations effectively block both the pyrimidine biosynthetic and salvage pathways
      and in combination are lethal to the host. Therefore, a plasmidencoded URA3 gene
      is essential for cell viability regardless of the growth conditions, and complex
      (traditionally nonselective) media can be employed without the risk of plasmid
      loss. The effects of medium enrichment on growth and cloned gene product
      synthesis were examined in batch culture for two autoselection strains. The
      plasmid gene product beta-galactosidase was under the control of the yeast GAL1
      promoter, and two methods of induction were employed; one strain was induced via
      temperature shift while the other was induced by galactose addition. Three
      nutrient media were investigated: a lean selective medium (SD), a richer
      semidefined medium (SDC), and a rich complex medium (YPD). The results
      demonstrated the improvements in cloned gene productivity possible when the
      growth medium is enriched, with up to 10-fold increases in beta-galactosidase
      productivity observed. Plasmid instability and mutation reversion were not
      problems for the autoselection strains, even in uracil-containing medium. Short
      term plasmid stabilities were approximately 90% in all three media tested. During
      continuous culture of the autoselection temperature-sensitive strain, long-term
      plasmid stability was excellent and beta-galactosidase expression remained high
      after more than 25 residence times under inducing conditions. In contrast, both
      beta-galactosidase specific activity and plasmid stability decreased linearly
      with time for an analogous nonautoselection strain. The introduced fur1 and uridk
      mutations were very stable; after more than 50 generations of growth in complex
      medium, stability values of 99-100% were measured.

PMID- 18609625
TI  - Population and biomass kinetics in fed-batch cultures of Daucus carota L. somatic
      embryos.
AB  - The population dynamics of developing somatic embryos of carrot (Daucur carota
      L.) was investigated in batch and fed-batch cultures using modified Murashige and
      Skoog medium. These substrate limitations coincided not only with stoppage of
      biomass increase, but also with the increase in total concentration of embryos as
      well as the advancement of the embryo into a more mature stage. Both glucose and
      ammonium were depleted from the culture. Restoring either glucose, or ammonium
      and nitrate, as to approximately initial concentrations in fed-batch experiments,
      did not result in a significant increase of the total normal embryo
      concentration. On the other hand, medium replacement led to increase in biomass
      concentration, total embryo number, and improved embryo maturity. The addition of
      a mixture of glucose, ammonium, and nitrate to the spent medium resulted in
      variable increases in biomass and embryo number, but always less than those
      resulting from media replacement. Although the total number of embryos was higher
      after medium replacement, the fraction of embryos reaching torpedo stage was
      still only 50%. The need for a better means of population characterization for
      further kinetic studies is discussed.

PMID- 18609626
TI  - Biosorption of cadmium by biomass of marine algae.
AB  - Biomass of nonliving, dried brown marine algae Sargassum natans, Fucus
      vesiculosus, and Ascophyllum nodosum demonstrated high equilibrium uptake of
      cadmium from aqueous solutions. The metal uptake of cadmium from aqueous
      solutions. The metal uptake by these materials was quantitatively evaluated using
      sorption isotherms. Biomass of A. nodosum accumulated the highest amount of
      cadmium exceeding 100 mg Cd(2+)/g (at the residual concentration of 100 mg Cd/L
      and pH 3.5), outperforming a commercial ion exchange resin DUOLITE GT-73. A new
      biosorbent material based on A. nodosum biomass was obtained by reinforcing the
      algal biomass by formaldehyde cross-linking. The prepared sorbent possessed good
      mechanical properties, chemical stability of the cell wall polysaccharides and
      low swelling volume. Desorption of deposited cadmium with 0.1-0.5M HCI resulted
      in no changes of the biosorbent metal uptake capacity through five subsequent
      adsorption/desorption cycles. There was no damage to the biosorbent which
      retained its macroscopic appearance and performance in repeated metal
      uptake/elution cycles.

PMID- 18609627
TI  - Cadmium biosorption by Saccharomyces cerevisiae.
AB  - Cadmium uptake by nonliving and resting cells of Saccharomyces cerevisiae
      obtained from aerobic or anaerobic cultures from pure cadmium-bearing solutions
      was examined. The highest cadmium uptake exceeding 70 mg Cd/g was observed with
      aerobic baker's yeast biomass from the exponential growth phase. Nearly linear
      sorption isotherms featured by higher sorbing resting cells together with metal
      deposits localized exclusively in vacuoles indicate the possibility of a
      different metal-sequestering mechanism when compared to dry nonliving yeasts
      which did not usually accumulate more than 20 mg Cd/g. The uptake of cadmium was
      relatively fast, 75% of the sorption completed in less than 5 min.

PMID- 18609628
TI  - Computation of pH evolution versus ionic products concentration in a fermentation
      broth.
AB  - An algorithm developed for pH computation has been tested to calculate the
      theoretical pH changes in a culture medium during the course of a fermentation. A
      divergence between the computed pH value and the value measured with the
      electrode allows us to highlight the presence of undetected ionic products. The
      calculation with the algorithm by means of a computer requires only the knowledge
      of the ionic properties of the substrates and detected products and existing
      thermodynamic constants.

PMID- 18609629
TI  - The adsorptive immobilization of phospholipids D mediated by calcium ions.
AB  - Immobilization of phospholipase D from cabbage was studied with the aim of
      stabilizing the enzyme for its use in synthesis of phospholipids. It was shown
      that phospholipase D can be immobilized by adsorption to polymeric carriers
      containing long chain anchor groups such as octadecyl, octyl, or other alkyl
      residues. Starting from the crude enzyme, phospholipase D activity is
      preferentially bound (up to 100%) in competition with contaminating proteins. A
      prerequisite of high binding rates is the presence of calcium ions, which play a
      mediating role in the adsorption process. The maximum activity of the carrier
      enzyme complexes depends upon the calcium concentration in the immobilization
      process and the carrier material (> or = 10 mM CaCl(2) with octadecyl-Si40, > or
      = 40 mM CaCl(2) with octyl-sepharose and butyl-fractogel). Immobilization of
      phospholipase D to octyl-sepharose was shown to result in a distinctly increased
      storage stability and an enlarged pH-optimum range for the catalytic activity.
      Operational stability of different phospholipase D-carrier complexes was
      compared.

PMID- 18609631
TI  - Broad host range, regulated expression system utilizing bacteriophage T7 RNA
      polymerase and promoter.
AB  - An IPTF-regulated broad host range expression system was constructed using
      compatible broad host range plasmids, the T7 RNA polymerase, and T7 promoter
      sequences. The system is implemented by the coexistence of two plasmids. The
      first contains the T7 RNA polymerase gene under the control of lacl or lacl(q)
      genes and lacUV5 promoter. The second encodes the T7 promoter upstream of a
      multicloning site. IncP1 or IncP4 T7 promoter plasmids, and IncP1, IncP4 or IncW
      T7 RNA polymerase plasmids were constructed. The expression from the IncP1
      promoter plasmids in the presence of the IncP4 polymerase plasmids was tested by
      in vivo lacZ fusions and vivo labeling of proteins. In this combination, the use
      of lac(q) improves the regulation levels in Escherichia coli, whereas, in
      Pseudomonas phaseolicola, a 28.5-fold regulation was obtained with lacl, Although
      the level of lacZ expression from the T7 promoter in P. phaseolicola is low
      compared with E. coli, it is similar to levels obtained with the pm promoter in
      Pseudomonas putida when the differences in the copy number of the expression
      vectors are taken into consideration.

PMID- 18609632
TI  - Study of the enzymatic hydrolysis of cellulose for production of fuel ethanol by
      the simultaneous saccharification and fermentation process.
AB  - The biochemical conversion of cellulosic biomass to ethanol, a promising
      alternative fuel, can be carried out efficiently and economically using the
      simultaneous saccharification and fermentation (SSF) process. The SSF integrates
      the enzymatic hydrolysis of cellulose to glucose, catalyzed by the synergistic
      action of cellulase and beta-glucosidase, with the fermentative synthesis of
      ethanol. Because the enzymatic step determines the ethanol. Because the enzymatic
      step determines the availability of glucose to the ethanologenic fermentation,
      the kinetic of cellulose hydrolysis by cellulase and beta-glucosidase and the
      susceptibility of the two enzymes to inhibition by hydrolysis and fermentation
      products are of significant importance to the SSF performance and were
      investigated under realistic SSF conditions. A previously developed SSF
      mathematical model was used to conceptualize the depolymerization of cellulose.
      The model was regressed to the collected data to determine the values of the
      enzyme parameters and was found to satisfactorily predict the kinetics of
      cellulose hydrolysis. Cellobiose and glucose were identified as the strongest
      inhibitors of cellulase and beta-glucosidase, respectively. Experimental and
      modeling results are presented in light of the impact of enzymatic hydrolysis on
      fuel ethanol production.

PMID- 18609633
TI  - Comparison of three different promoter systems for secretory alpha-amylase
      production in fed-batch cultures of recombinant Saccharomyces cerevisiae.
AB  - Cloned gene expression in recombinant Saccharomyces cerevisiae 20B-12 containing
      three different plasmids was compared in batch and fed-batch cultures. The
      plasmids pNA3, pNA7, and pNA9 contain the alpha-amylase gene under the control of
      SUC2, PGK, and GAL7 Promoters, respectively. The synthesis of alpha-amylase was
      therefore induced by low glucose concentration for the SUC2 and PGK promoters,
      and by galactose for GAL7 promoter. The specific cell growth rates were similar
      among cells harboring the three different plasmids; they decreased from 0.35 to
      0.38 h(-1) during the cell growth phase to 0.03 to 0.06 h(-1) during the
      production phase. The secretory alpha-amylase activity of cells harboring plasmid
      pNA7 was 129 U/mL in fed-batch culture, which was 1.4 and 2 times as high as the
      activities of cells harboring plasmids pNA3 and pNA9, respectively. The secretion
      ratios (amount of extracellular alpha-amylase activity/amounts of total alpha
      amylase activity) of cells harboring plasmids pNA3, pNA7, and pNA9 were 91.4%,
      94.5%, and 95.3%, respectively.

PMID- 18609634
TI  - Homogeneous immunoassay of polyclonal antibodies by use of antigen-coupled
      liposomes.
AB  - Anti-cytochrome c and anti-myoglobin antibodies were assayed by use of
      immunoliposomes coupled with the antigens. Addition of complement under the
      existence of the antigens. Addition of complement under the existence of the
      antigen-antibody complex on the surface of the liposome caused lysis of the
      liposomes, which was proportional to the amount of the antigen-antibody complex
      formed as well as the concentration of complement added. Thus, the degree of
      marker release depended on the average association constant and also on its
      heterogeneity of the polyclonal antibodies, which shows that the results assayed
      by this method are correlated to the antibody ability to form the antigen
      antibody complex.

PMID- 18609635
TI  - Fluid-mechanical forces in agitated bioreactors reduce the CD13 and CD33 surface
      protein content of HL60 cells.
AB  - Flow cytometry was used to examine the effect of hydrodynamic forces in surface
      aerated stirred tank bioreactors on the quantity of CD13 and CD33 surface
      proteins of Hl60 (human promyelocytic leukemia) cells. A step increase in
      agitation of the 2-L bioreactors from 80 to 400 rpm reduced the apparent growth
      rate and the average CD13 and CD33 content per HL60 cell. The effects on the two
      surface proteins were observed within 30-60 min following the increase in the
      agitation and preceded observed effects on cell growth by at least 10 h. Upon
      reduction of the agitation rate back to 80 rpm, the CD13 and CD33 content
      recovered (in ca. 10 h) for CD13 and ca. 29h for (CD33) to the levels of the
      control culture whose agitation rate was maintained at 80rpm. The CD13 and CD33
      cell content was reduced even at agitation rates (270 rpm) that did not affect
      cell proliferation. Pluronic F68 (a commonly used shear protectant) had a
      protective effect on the CD33 content per cell of cultures subjected to
      hydrodynamic injury but no effect on the CD13 cell content. Possible
      bioprocessing and physiological implications of these findings are discussed.

PMID- 18609636
TI  - Purification and characterization of a highly thermostable glucose isomerase
      produced by the extremely thermophilic eubacterium, Thermotoga maritima.
AB  - Thermotoga maritima, among the most thermophilic eubacteria currently known,
      produces glucose isomerase when grow in the presence of xylose. The purified
      enzyme is a homotetramer with submit molecular Wight of about 45,000. It has a
      number of features in common with previously described glucose isomerases-pH
      optimum of 6.5 to 7.5, presence of active-site histidine, requirement for metal
      cations such as Co(2+) and Mg(2+), and preference for xylose as substrate. In
      addition, it has significant sequence/structural homology with other glucose
      isomerases, as shown by both N-terminal sequencing and immunological
      crossreactivity. The T. maritima enzyme is distinguished by its extreme
      thermostability-a temperature optimum of 105 to 110 degrees C, and an estimated
      half-life of 10 minutes at 120 degrees C, pH 7.0. The high degree of
      thermostability, coupled with a neutral to slightly acid pH optimum, reveal this
      enzyme to be a promising candidate for improvement of the industrial glucose
      isomerization process.

PMID- 18609637
TI  - Factor affecting enzyme characteristics of bilirubin oxidase suspensions in
      organic solvents.
AB  - The activity of bilirubin oxidase toward bilirubin was studied in a liquid/solid
      two-phase low-water organic system using a simple spectrophotometric assay to
      follow the reaction. The enzyme was lyophilized from aqueous solution before
      being suspended in the organic solvent reaction medium. The activity was
      significantly influenced by the properties of the aqueous medium from which the
      enzyme was lyophilized, specifically its pH, and the quantity and nature of the
      buffering species. Analyses of these effect showed that the role of buffering
      species in such systems went beyond their effect in fixing the protonation state
      of the enzyme. The activity was also influenced by the quantity of water added to
      the organic solvent reaction medium. The reaction was shown to follow Michaelis
      Menten Kinetics, and K(m) and k(cat) were determined. The liquid/solid two-phase
      system studied was extensively compared to a previously studied water-in-oil
      microemulsion system.

PMID- 18609638
TI  - Stability of bilirubin oxidase in organic solvent media: a comparative study on
      two low-water systems.
AB  - The storage stability of bilirubin oxidase was studied in water-in-oil CTAB
      microemulsions with a chloroformrich continuous organic phase. The kinetics of
      the inactivation process were best described by a double exponential equation.
      Approximately half of enzymatic activity was lost during a "fast" phase with a
      half life of ca. 50 min, whereas the remaining activity was lost much more slowly
      (half life ca. 1000 min). Rates of inactivation were not affected significantly
      by variation of either solvent composition or concentration of water droplets,
      but inactivation was more rapid when droplet size was very small. Steady-state
      enzyme kinetics were studied at various stages in the inactivation process, and
      it was shown that inactivation occurred without change in the K(m) of the enzyme
      for bilirubin. Stability was also studied in a liquid/solid two-phase system; it
      was found that the inactivation process in this system; it was found that the
      inactivation process in this system was best described by a single exponential
      term. The rate was similar to the "fast" phase rate observed in the water-in-oil
      microemulsion system. Inactivation of the enzyme slow. Addition of the surfactant
      CTAB to the aqueous environment increased the rate of inactivation to levels
      comparable to those of the "slow" phase observed in water-in-oil microemulsions.

PMID- 18609639
TI  - Complete design analysis of a continuous sterilizer for fermentation media
      containing suspended solids.
AB  - An improved mathematical model was developed to design a continuous sterilizer
      for liquid fermentation media containing suspended solids. Unsteady-state energy
      balances were used to determine the temperature distribution in the liquid medium
      and in the solid particles as a function of time and position within the
      particle, as the medium flows through the sterilizer. Such temperature profiles
      were used to determine the level of microbial reduction achieved by each
      component of the sterilizer and by the entire sterilization process. A
      considerable difference exists between the temperature in the particle core and
      in the surrounding liquid. This has a significant impact on the degree of
      sterility achieved by the process. The level of microbial reduction in the
      particles was found to be tens and or even hundreds of order of magnitude lower
      than the corresponding level achieved in the liquid. The role of the particle
      material on the degree of sterilization was also investigated. Solid materials
      typically found in fermentation media, such as wood or flour clumps were found to
      offer considerable resistance to the sterilization of the organisms lodged inside
      them.

PMID- 18609641
TI  - Symmetric branching model for the kinetics of mycelial growth.
AB  - A mathematical model, linking microscopic to macroscopic parameters of the
      kinetics of mycelial growth is presented. The model consists of two parts: (a) a
      microscopic description, based on the assumption that growth of a mycelium can be
      represented approximately by the growth of a symmetric binary tree, where the
      branching level (microscopic state variable) is logarithmically related to the
      number of tips and segments; and (b) a macroscopic description which makes use of
      the microscopic description in order to define the parameters related to the
      evolution of biomass (macroscopic state variable) as a function of time. The
      latter uses a distribution of arrested tips in a population of mycelia, in order
      to estimate the fraction of non-growing biomass in terms of a power law function
      with coefficient, n, of the biomass concentration. The microscopic description
      explains the fact that the germ tube specific growth rate of Aspergillus nidulans
      measured in a growth chamber, is about the double the specific growth rate of
      this organism, when measured in shake flasks. It predicts that the length of the
      hyphal growth unit of the mycelium of Geotrichum candidum would be approximately
      the double the germ tube length measured at the time just before the first
      branching event. It also allows the derivation of useful expressions for
      predicting macroscopic parameters, such as the maximal specific growth rate, the
      initial amount of biomass, and the amount of biomass before the branching process
      starts. Those estimates are done in terms of microscopic quantities, i.e., the
      amount of germinated spores, the diameters of the spores and hyphae, the average
      rate of tip extension, and the average internodal segment length. Estimation of
      coefficient n by fitting the macroscopic description to a growth curve of A.
      niger gives an indication on the degree of skewness of the distribution of
      arrested mycelia. Estimated macroscopic parameters are in relative good agreement
      with measured average segment length.

PMID- 18609642
TI  - Viability testing and characterization of germination of fungal spores by
      automatic image analysis.
AB  - Fungal spores are used in the laboratory for culture maintenance and at
      laboratory and other scales as inocula for fermentations. The spore swelling and
      germination processes constitute a major part of the lag phase, and the
      subsequent culture morphology and productivity can be greatly influenced by the
      initial concentration and condition of the spores. An image analysis method has
      been developed for assessing the viability and the germination characteristics of
      fungal spores in submerged cultures. Structural variations during germination,
      i.e., swelling, germ tube formation, and germ tube elongation, are measured in
      terms of distributions of spore volumes and of germ tube lengths and volumes.
      These measurements are fully automatic and give a very rapid assessment of spore
      viability. This image analysis method might be used as a tool in culture
      maintenance and for determining the quality of inocula for fungal fermentations.

PMID- 18609643
TI  - Transport and intracellular accumulation of acetaldehyde in saccharomyces
      cerevisiae.
AB  - The rate of acetaldehyde efflux from yeast cells and its intracellular
      concentration were studied in the light of recent suggestions that acetaldehyde
      inhibition may be an important factor in yeast ethanol fermentations. When the
      medium surrounding cells containing ethanol and acetaldehyde was suddenly
      diluted, the rate of efflux of acetaldehyde was slow relative to the rate of
      ethanol efflux, suggesting that acetaldehyde, unlike ethanol, may accumulate
      intracellularly. Intracellular acetaldehyde concentrations were measured during
      high cell density fermentations, using direct injection gas chromatography to
      avoid the need to concentrate or disrupt the cells. Intracellular acetaldehyde
      concentrations substantially exceeded the extracellular concentrations throughout
      fermentation and were generally much higher than the acetaldehyde concentrations
      normally recorded in the culture broth in ethanol fermentations. The technique
      used was sensitive to the time taken to cool and freeze the samples. Measured
      intracellular acetaldehyde concentrations fell rapidly as the time taken to
      freeze the suspensions was extended beyond 2 s. The results add weight to recent
      claims that acetaldehyde toxicity is responsible for some of the effects
      previously ascribed to ethanol in alcohol fermentations, especially Zymomonas
      fermentations. Further work is required to confirm the importance of acetaldehyde
      toxicity under other culture conditions.

PMID- 18609644
TI  - In situ fermentation monitoring with recombinant firefly luciferase.
AB  - A novel method is described for the on-line determination of viable cell number.
      It has been tested in fermentations of Escherichia coli. The cells are
      transfected with the gene for firefly luciferase and fed low levels of luciferin
      in the medium. The reaction requires ATP, so the nonviable cells cannot produce
      light. Thus, light production is linear with viable cell density from
      innoculation through most of exponential growth. The light emitted by these cells
      is then conducted from the reaction vessel to the light detection equipment by an
      optical fiber. With the equipment described below, as few as a 10(6) cells/mL, or
      an OD(600) of 0.004, are easily detectable and concentrations greater than 10(10)
      cells/mL are well within range. The data are collected by a computer, so
      adaptation to on-line control applications is straightforward. During lag phase,
      this method is much more accurate then optical density measurements. At the end
      of exponential growth, rapid changes in light production mark carbon source
      depletion and the onset of cell lysis. A simple model accounts for the luciferin
      used during the fermentation and corrects the light detected to the proper cell
      density.

PMID- 18609645
TI  - Effect of fluorochrome location in protein A on sensing efficiency of IgG.
AB  - Fragment B of protein A conjugated with fluorescein at various lysine residues is
      prepared and separated by using a DEAE column in anion-exchange chromatography.
      The binding of IgG Fc to fragment B contributes to an additional positive
      electric potential around fragment B. The change in the local electrostatic
      environment and pH can then be specifically monitored by measuring the
      fluorescence intensity of fluorescein conjugated with fragment B before and after
      the introduction of IgG. The studies for the quantitative dependence of
      fluorescein location on the effectiveness of fluorescein for sensing the protein
      A-IgG reaction are presented and discussed.

PMID- 18609646
TI  - Regeneration of NADH in a bioreactor using yeast cells immobilized in alginate
      fiber: I. Method and effect of reactor variables.
AB  - Saccharomyces cerevisiae cells immobilized in a calcium alginate fiber reactor
      were used as a source of alcohol dehydrogenase for the NAD(+)-to-NADH reaction.
      The reaction was catalyzed by enzyme in cells on the surface of the fiber.
      Internal diffusional effects were present. The enzyme cell concentration was
      optimized by harvesting cells finally grown under anaerobic conditions. The
      results were expressed as an apparent reaction rate constant that was independent
      of NAD(+) and excess ethanol concentration, was slightly affected by flow rate
      above a minimum value, and increased with immobilized cell concentration in the
      fiber. The reaction was complete after 6 to 7 h under optimal conditions of 36
      degrees C and 9.5 pH. The latter was 0.5 pH units above the free enzyme optimum,
      indicating that microenvironmental effects were in evidence.

PMID- 18609647
TI  - Emulsion liquid membrane extraction of lactic acid from aqueous solutions and
      fermentation broth.
AB  - Studies on the batch extraction of lactic acid using an emulsion liquid membrane
      system are reported. The membrane phase consists of the tertiary amine carrier
      Alamine 336 and the surfactant Span 80 dissolved in n-heptane/paraffin and
      aqueous solutions of sodium carbonate in the internal phase. The effects of
      internal phase reagent, extraction temperature, and initial external phase pH on
      the extraction efficiency and the emulsion swelling are examined. A statistical
      factorial experiment on extraction from clarified lactic acid fermentation broth
      was carried out to obtain knowledge of the performance of the extraction system
      from a broth. The extraction efficiency from the fermentation broth is found to
      be lower as compared to aqueous solutions of pure lactic acid. The effect of pH
      and the presence of other ionic species on selectivity are discussed.

PMID- 18609648
TI  - Biochemical production capabilities of Escherichia coli.
AB  - Microbial metabolism provides at mechanism for the conversion of substrates into
      useful biochemicals. Utilization of microbes in industrial processes requires a
      modification of their natural metabolism in order to increase the efficiency of
      the desired conversion. Redirection of metabolic fluxes forms the basis of the
      newly defined field of metabolic engineering. In this study we use a flux balance
      based approach to study the biosynthesis of the 20 amino acids and 4 nucleotides
      as biochemical products. These amino acids and nucleotides are primary products
      of biosynthesis as well as important industrial products and precursors for the
      production of other biochemicals. The biosynthetic reactions of the bacterium
      Escherichia coli have been formulated into a metabolic network, and growth has
      been defined as a balanced drain on the metabolite pools corresponding to the
      cellular composition. Theoretical limits on the conversion of glucose, glycerol,
      and acetate substrates to biomass as well as the biochemical products have been
      computed. The substrate that results in the maximal carbon conversion to a
      particular product is identified. Criteria have been developed to identify
      metabolic constraints in the optimal solutions. The constraints of stoichiometry,
      energy, and redox have been determined in the conversions of glucose, glycerol,
      and acetate substrates into the biochemicals. Flux distributions corresponding to
      the maximal production of the biochemicals are presented. The goals of metabolic
      engineering are the optimal redirection of fluxes from generating biomass toward
      producing the desired biochemical. Optimal biomass generation is shown to
      decrease in a piecewise linear manner with increasing product formation. In some
      cases, synergy is observed between biochemical production and growth, leading to
      an increased overall carbon conversion. Balanced growth and product formation are
      important in a bioprocess, particularly for nonsecreted products.

PMID- 18609649
TI  - Overexpression of cloned genes using recombinant Escherichia coli regulated by a
      T7 promoter: II. Two-stage continuous cultures and model simulations.
AB  - A two-stage culture strategy was studied for continuous high-level production of
      a foreign protein in the chemically inducible T7 expression system. The first
      stage is dedicated to the maintenance of plasmid-bearing cells and the second
      stage to the target protein synthesis by induction of cells coming from the first
      stage. On entering the second stage, recombinant cells undergo a gradual
      induction of the target gene expression. These plasmid-bearing cells experience
      dynamic changes in intracellular compositions and specific growth rates with
      their individual residence times. Therefore, the overall cultural characteristics
      in the production stage are really averages of the contributions from the various
      cells with different residence times. The behavior of the two-stage culture is
      described by a model, which accounts for dynamic variations of cell growth and
      protein synthesis rates with cell residence times. Model simulations were
      compared with experimental results at a variety of operating conditions such as
      inducer concentration and dilution rate. This model is useful for understanding
      the behavior of two-stage continuous cultures.

PMID- 18609650
TI  - Construction, expression, and analysis of recombinant HIV gp41 constructs
      containing a novel cellular binding domain.
AB  - The gp41 polypeptide of human immunodeficiency virus (HIV) contains an
      immunosuppressive domain, an epitope which elicits specific cytolytic T cell
      responses to HIV, and a complement Clq interactive domain. In addition, a
      synthetic peptide called CS3, derived from gp41 (amino acids 576-593 of gp160)
      and contiguous with the major immunodominant domain, binds to cellular proteins
      and may be important in HIV entry/fusion. In order to further investigate the
      role of the CS3 region of gp41 in cellular binding and to investigate other
      properties of gp41, sufficient quantities of this polypeptide must be readily
      available. We have therefore cloned the region of the HIV genome between
      nucleotides 7891 and 8188 (corresponding to amino acids 541-639 of gp160) into a
      series of procaryotic expression vectors. The resulting clones express a
      recombinant polypeptide of gp41 (r41). Two of these recombinants, pMAL-cRl/r41
      and pGEMEX-2/r41, expressed the highest and most consistent levels of r41 as
      judged by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and Western blot analysis. With the pMAL-cRl/r41 construct, r41 was
      expressed as a fusion to the maltose-binding protein (MBP) and, following
      purification by affinity chromatography, was cleaved from MBP by factor Xa
      protease digestion. MBP/r41 may be useful for studies of a reported gp41 cellular
      binding domain and may facilitate studies involving other functions ascribed to
      this region of gp41.

PMID- 18609651
TI  - Solid-state nuclear magnetic resonance investigation of solvent dependence of
      tyrosyl ring motion in an enzyme.
AB  - Tyrosyl ring motions in alpha-lytic protease were investigated by solid-state
      deuterium nuclear magnetic resonance (NMR) spectroscopy in lyophilized enzyme
      powder, in powder suspended in organic solvents, and in aqueous crystals. Ring
      flipping rates were determined by examining deuterium quadrupole echo line
      shapes. Of the four Tyr residues in the enzyme, one was flipping at the slow (<
      or =10(3) s(-1)) and one at the fast (> or =10(7) s(-1)) exchange limit of the
      line shape experiment in all the environments tested. Flipping rates of the
      remaining two Tyr residues depended markedly on the solvent, with the lowest
      flipping rates (< or =10(3) s(-1) for both residues) observed in the enzyme
      powder, whether dry or suspended in hydrophobic tert-butyl methyl ether. In
      hydrophilic dioxane and acetonitrile, the mobility of these residues increased to
      10(4) and 10(5) s(-1). The latter rate rose further to 10(6) s(-1) in the
      hydrated hydrophilic solvents and to > or =10(7) s(-1) in aqueous crystals. The
      deuterium spectrum of native alpha-lytic protease was compared with that of the
      enzyme whose active center was covalently modified with an inhibitor, which binds
      next to Tyr-123, constraining its ring. This experiment revealed that water
      addition to acetonitrile specifically increased the flipping rate of this active
      center residue. Librational motions ("wobbling"), estimated by their effect on
      spin-lattice relaxation times, were slowest in the anhydrous solvents,
      intermediate in the hydrated solvents, and fastest in the aqueous crystals. Thus,
      alpha-lytic protease is more rigid in organic solvents than in water, as judged
      by mobility of its tyrosyl residues. Water stripping by hydrophilic solvents did
      not increase enzyme rigidity, nor were there clear correlations between mobility
      and either enzymatic activity or solvent dielectric constant.

PMID- 18609652
TI  - Improved protein synthesis and secretion through medium enrichment in a stable
      recombinant yeast strain.
AB  - Two Saccharomyces cerevisiae strains were employed to investigate the effects of
      medium enrichment on the expression and secretion of a recombinant protein. One
      was a stable autoselection strain with mutations in the ura3, fur1, and urid-k
      genes. The combination of these three mutations blocks both the pyrimidine
      nucleotide biosynthetic and salvage pathways and is lethal to the cells.
      Retention of the plasmid, which carries a URA3 gene, was essential for cell
      viability. Therefore, all media were selective, allowing cultivation of the
      strain in complex medium. The second strain was a nonautoselection (control)
      strain and is isogenic to the first except for the fur1 and urid-k mutations. The
      plasmid utilized contains the yeast invertase gene under the control of the
      MFalpha1 promoter and leader sequence. The expression and secretion of invertase
      for the autoselection strain were examined in batch culture for three media: a
      minimal medium (SD), a semidefined medium (SDC), and a rich complex medium (YPD).
      Biomass yields and invertase productivity (volumetric activity) increased with
      the complexity of the medium; total invertase volumetric activity in YPD was 100%
      higher than in SDC and 180% higher than in SD. Specific activity, however, was
      lowest in the SDC medium. Secretion efficiency was extremely high in all three
      media; for the majority of the culture, 80-90% of the invertase was secreted into
      the periplasmic space and/or culture medium. A glucose pulse at the end of batch
      culture in YPD facilitated the transport of residual cytoplasmic invertase. For
      the nonautoselection strain, invertase productivity did not improve as the medium
      was enriched from SDC to YPD, and plasmid stability in the complex YPD medium
      dropped from 54% to 34% during one batch fermentation. During long-term
      sequential batch culture in YPD, invertase activity decreased by 90% and the
      plasmid-containing fraction dropped from 56% to 8.8% over 44 generations of
      growth. The expression level for the autoselection strain, however, remained high
      and constant over this time period, and no reversion at the fur1 or urid-k locus
      was observed.

PMID- 18609653
TI  - Esterification reactions catalyzed by lipases in microemulsions: the role of
      enzyme localization in relation to its selectivity.
AB  - The activity of lipases from Rhizopus delemar, Rhizopus arrhizus, and Penicillium
      simplicissimum entrapped in microemulsions formulated by bis-(2-ethylhexyl)sulfo
      succinate sodium salt (AOT) in isooctane has been studied in esterification
      reactions of various aliphatic alcohols with fatty acids. The effect of the
      nature of the fatty acids (chain length) and of the alcohols (primary, secondary,
      or tertiary; chain length; cyclic structures) on the lipase activities was
      investigated in relation to the reverse micellar structure. The lipases tested
      showed a selectivity regarding the structure of the substrates used when hosted
      in the AOT/isooctane microemulsion systems. Penicillium simplicissimum lipase
      showed higher reaction rates in the esterification of long chain alcohols as well
      as secondary alcohols. Primary alcohols had a low reaction rate and tertiary a
      very slow rate of esterification. Long chain fatty acids were better catalyzed as
      compared to the shorter ones. Rhizopus delemar and R. arrhizus lipases showed a
      preference for the esterification of short chain primary alcohols, while the
      secondary alcohols had a low rate of esterification and the tertiary ones could
      not be converted. The reaction of medium chain length fatty acids was also better
      catalyzed than in the case of the long ones. The observed lipase selectivity
      appeared to be related to the localization of the enzyme molecule within the
      micellar microstructure due to the hydrophobic/hydrophilic character of the
      protein. The reverse micellar structural characteristics, as well as the
      localization of the enzyme, were examined by fluorescence quenching measurements
      and spectroscopical studies.

PMID- 18609654
TI  - Transport of 1-microm latex particles in pseudomonas aeruginosa biofilms.
AB  - Fluorescent latex microbeads added to a Pseudomonas aeruginosa biofilm as tracers
      of particle movement penetrated the biofilm and remained in it much longer than
      predicted by a model of advective displacement due to cell growth. Beads with a
      nominal diameter of 1 mum that were added in the bulk fluid became distributed
      throughout the biofilm depth. Some microbeads penetrated to the substratum within
      the 24-h bead addition period. The biofilms had a mean thickness of approximately
      34 mum but have been previously shown to be quite rough. Measured rates of bead
      release from the biofilm corresponded to first order time coefficients of 0.01
      0.03 h(-1). These bead release rates were approximately an order of magnitude
      less than the predicted time scale of advective transport, which is just the
      experimentally measured specific cellular growth rate of 0.15 h(-1). Computer
      simulations of bead transport using the biofilm model BIOSIM were compared with
      bead release rate data and with bead position distributions within the biofilm as
      determined by microscopic examination of thin cross sections of embedded biofilm.
      The model predicted much faster release of beads from the biofilm than actually
      occurred. It is hypothesized that both the ability of beads to penetrate the
      biofilm and the unexpectedly low advective displacement velocity of particles in
      the biofilm were due to the rough nature of the biofilm.

PMID- 18609655
TI  - Comparison of soluble and immobilized trypsin kinetics: Implications for peptide
      synthesis.
AB  - The protease trypsin was immobilized to porous glass in both the presence and
      absence of acetylated soybean trypsin inhibitor (STI) to determine whether
      immobilization could alter enzyme activity in favor of aminolysis over
      hydrolysis. Actiive-site titration with 4-methylumbelliferylguanidinobenzoate
      (MUGB) showed that only about 10% of immobilized trypsin had catalytic activity.
      Immobilization in the presence of STI produced a higher yield of active enzyme
      accessible to the inhibitor but did not increase the total yield of MUGB-active
      immobilized enzyme. Thus, enzyme inactivation upon immobilization could not be
      attributed to an inaccessible enzyme orientation, nor did STI prevent
      inactivation by stabilizing the active-site conformation. Kinetic parameters were
      determined for soluble and immobilized trypsin for two esters, N-tosyl-L-arginine
      methyl ester (TAME) and N-benzoyl-L-arginine ethyl ester (BAEE), and two amides,
      N-benzoyl-L-arginine p-nitroanilide (BAPNA) and N-t-boc-leucylglycylarginine p
      nitroanilide (LGRNA). In all cases, immobilization caused a greater decrease in
      k(cat) for amidase activity than for esterase activity. The ratio [k(cat)/ K(m)
      (ester)]/[k(cat)/K(m) (amide)] increased slightly or stayed the same (for I.GRNA)
      or decreased sharply (for BAPNA). Including STI during immobilization had little
      effect on the active enzyme's intrinsic kinetics. A direct comparison of energy
      diagrams and free energies of activation for BAEE and BAPNA indicates that
      immobilization raises the free energy barriers for both amide and ester
      hydrolysis and lowers the energy barrier for aminolysis. In practice, these
      effects should lower the amidase activity and increase the aminolysis-hydrolysis
      ratio, rendering the immobilized enzyme a more efficient catalyst for peptide
      synthesis.

PMID- 18609656
TI  - Sterilization of various diameter dead-ended tubes.
AB  - Effect of tube diameter on steam-in-place sterilization of dead-ended tubes was
      studied by examining temperature profiles and rates of kill of Bacillus
      stearothermophilus spores. Time required for sterilization was determined for 9.4
      cm-long tubes with various inside diameters from 0.4 to 1.7 cm. Sterilization
      time increased with decreasing tube diameter. Experimentally measured kill
      kinetics in 1.7-cm tubes were in agreement with those predicted if measured
      temperatures represented saturated steam. A 12-log spore reduction was achieved
      in 1.7-cm diameter vertical and horizontal tubes in less than 63 minutes. For
      smaller diameter tubes, entrapped air remained after 2 hours and rates of kill
      were very dependent on position within the tube, tube diameter, and tube
      orientation with respect to the gravitational vector. Times to achieve a 1-log
      drop in spore population in the smaller tubes were as much as 10 times greater
      than those expected if measured temperatures represented saturated steam.
      Sterilization was not achieved throughout the 0.4-cm tubes. Recommendations are
      made for including steam bleeders or using prevaccum cycles for these smaller
      diameter tubes.

PMID- 18609657
TI  - A three-phase pattern in growth, monoclonal antibody production, and metabolite
      exchange in a hybridoma bioreactor culture.
AB  - The use of partial cubic spline data interpolation for the calculation of
      volumetric metabolite exchange rates suggested the existence of three distinct
      metabolic phases during bioreactor culture of a hybridoma cell line. During phase
      1, a rapid amino acid uptake rate and ammonia release rate were observed. The
      growth rate was low and glutamine synthetase activity fell. In phase 2, maximum
      growth rate and minimum glutamine assimilation and ammonium production rates were
      observed. Attempts to corroborate the apparent ammonia assimilation in this phase
      using (15)NH(4)Cl resulted in low incorporation rates into alanine and glutamine.
      Maximum glutamine synthetase activity took place during this period. Maximum
      antibody production rate was observed during phase 3 during which peaks in
      glutamine assimilation, ammonia release, and glutamine synthetase activity were
      observed. The apparent existence of the three phases prompted us to carry out
      Northern blot analysis of glutamine synthetase RNA at appropriate times during
      the process. This revealed a pattern of appearance and dis-appearance of mRNA
      consistent with the three phases indicated by the fermentation parameters.

PMID- 18609658
TI  - Micelle-supported electroenzymology: Succinate dehydrogenation by escherichia
      coli fumarate reductase in decylubiquinone and octyl glucoside micelles.
AB  - The concept of micelle-supported electroenzymology is demonstrated using a system
      consisting of the membrane enzyme Escherichia coli fumarate reductase (FRD), the
      amphiphilic coenzyme analogue decylubiquinone (DU), the micelle-forming
      surfactant n-octyl glucoside (OG), and a gold electrode. The OG micelles provide
      a hydrophobic, membrane mimetic medium for FRD and DU to exchange electrons while
      the gold electrode serves to regenerate DU. When succinate is presented to the
      FRD/DU/OG micelle system, electroenzymatic oxidation of succinate to fumarate
      occurs as evidenced using cyclic voltammetry. DU is shown to be the only
      electroactive species in the system; and as increasing amounts of succinate are
      added, the expected increase in the peak anodic (oxidative) current and decrease
      in the peak cathodic (reductive) current are observed. The peak anodic current
      approaches a limiting value with succinate concentration in qualitative agreement
      with simple Michaelis-Menten enzyme kinetics. When the strong competitive
      inhibitor oxaloacetate is added, enzymatic oxidation of succinate is inhibited as
      indicated by no change in the peak anodic and cathodic currents with increasing
      succinate concentration.

PMID- 18609659
TI  - A synergistic kinetics model for enzymatic cellulose hydrolysis compared to
      degree-of-synergism experimental results.
AB  - It is demonstrated that a two-enzyme component synergistic model can account for
      the observation that the degree of synergism goes through a maximum as the total
      enzyme concentration is increased. The degree of synergism is low at low enzyme
      concentration because the extent of conversion is low and therefore the cellulose
      chain ends, present originally, are not exhausted; thus the action of the
      cellobiohydrolase (CBH) is not dependent on the chain ends generated by the
      endoglucanase (EG). The degree of synergism declines at high enzyme concentration
      due to saturation of adsorption sites with CBH, thus decreasing the generation of
      chain ends by EG.

PMID- 18609661
TI  - Peroxidase and laccase as catalysts for removal of the phenylhydrazide protecting
      group under mild conditions.
AB  - A new method is proposed for the removal of the phenylhydrazide protecting group
      by the action of peroxidase or laccase, the enzymes attributed to the class of
      oxidoreductases. The deblocking procedure is performed under mild oxidative
      conditions, i.e., aqueous solution and neutral or close to neutral pH. Such mild
      oxidizing agents as 1 mM H(2)O(2) and air oxygen are used for unmasking. The
      method is available for the deblocking of both alpha- and gamma-carboxyl groups.
      The enzyme-catalyzed removal of the phenylhydrazide protecting group causes no
      oxidative modification nor destruction of methionine or tryptophan side chains.

PMID- 18609662
TI  - Enhanced production of alpha-amylase in fed-batch cultures of Bacillus subtilis
      TN106[pAT5].
AB  - Growth of Bacillus subtilis TN106[pAT5] and synthesis of plasmid-encoded protein
      (alpha-amylase) are investigated in batch, continuous, and fed-batch cultures
      using a defined medium containing glucose and/or starch as the carbohydrate
      source. The batch culture studies reveal that reduced availability of arginine
      hampers growth of recombinant cells (which lack an arginine synthesis gene) but
      promotes production of alpha-amylase and substitution of glucose by starch as the
      carbohydrate source leads to slower growth of recombinant cells and increased
      production of alpha-amylase per unit cell mass. Retention of recombinant cells
      over prolonged periods in continuous cultures is not possible without continuous
      application of antibiotic selection pressure owing to segregational plasmid
      instability. Fed-batch experiments with constant volumetric feed rate demonstrate
      that alpha-amylase production is enhanced at lower feed concentration of starch
      (sole carbohydrate source) and lower volumetric feed rate. Such slow addition of
      starch is however not conducive for growth of recombinant cells. The expression
      of the thermostable alpha-amylase gene carried on the recombinant plasmid pAT5
      (derived from a plasmid isolated from a thermophilic bacterium) is promoted at
      higher temperatures, while growth of recombinant cells is depressed. In all batch
      and fed-batch experiments, production of alpha-amylase is observed to be
      inversely related to growth of recombinant cells. The efficacy of two-stage
      bioreactor operations, with growth of recombinant cells being promoted in the
      first stage and alpha-amylase production in the second stage, in attaining
      increased bulk alpha-amylase activity is demonstrated.

PMID- 18609663
TI  - Efficiency of fatty acid synthesis by oleaginous yeasts: Prediction of yield and
      fatty acid cell content from consumed C/N ratio by a simple method.
AB  - In nitrogen-limited media, growth and fatty acid formation by the oleaginous
      yeast Rhodotorula glutinis, i.e., yield and fatty acid cell content, have been
      characterized regarding carbon and nitrogen availabilities. It was shown that the
      formation of fatty acid free biomass was limited by nitrogen availability,
      whereas the fatty acid production was directly dependent on the consumed C/N
      ratio. According to these observations, the fraction of substrate consumed for
      fatty acid synthesis was estimated by using a simple method based on the actual
      yields, i.e., the mass of carbon source strictly converted into fatty acids and
      fatty acid free biomass. From these results, relationships were established
      allowing to predict in a simple and performing manner the maximal attainable
      fatty acid cell content and yield from the available carbon and nitrogen. These
      relationships were validated by using experimental data obtained by various
      authors with different yeast strains, and the proposed method was compared to the
      energetic and mass balance method previously described.

PMID- 18609664
TI  - Membrane formation by interfacial cross-linking of chitosan for
      microencapsulation of Lactococcus lactis.
AB  - Lactic acid bacteria were microencapsulated within cross-linked chitosan
      membranes formed by emulsification/interfacial polymerization. The technique was
      modified and optimized to provide biocompatible conditions during encapsulation
      involving the use of mineral oils as the continuous phase and chitosan as the
      membrane material. Chitosan cross-linked with hexamethylene diisocyanate or
      glutaraldehyde resulted in strong membranes, with a narrow size distribution
      about a mean diameter of 150 mum. Cell viability and activity was demonstrated by
      the acidification of milk. Loss of acidification activity during
      microencapsulation was recovered in subsequent fermentations to levels similar to
      that of free cell fermentations.

PMID- 18609665
TI  - Factors affecting bio-oxidation of sulfide minerals at high concentrations of
      solids: a review.
AB  - Bio-oxidation has proved to be a viable process for the oxidative pretreatment of
      refractory gold-bearing sulfides. Generally, the oxidation rate is maximal at 20%
      solids for high sulfide content materials [ca. 30% sulfur]. Low grade ores [1%
      sulfur] have been successfully oxidized at 55% solids, indicating a link between
      the sulfide grade of the material and the optimal solids concentration for
      operation. Concentrations of high solids have been reported to lower oxidation
      rates, increase lag times, and decrease the ultimate extent of oxidation. This
      review discusses the various factors that have been proposed as causes of these
      phenomena. The factors include oxygen and carbon dioxide availability, low
      bacteria-solids ratio; mechanical damage or inhibition of the bacteria,
      inhibition of bacterial attachment, and the buildup of toxic leach products or
      other detrimental substances such as some flotation reagents.

PMID- 18609666
TI  - Self-cycling fermentation in a stirred tank reactor.
AB  - Self-cycling fermentations (SCFs) were conducted in a stirred tank apparatus
      using Bacillus subtilis and Acinetobacter calcoaceticus. The systems were very
      stable and the experiments lasted through many cycles. The variation of
      parameters such as biomass and doubling time from cycle to cycle was small. The
      stirred tank reactor (STR) allowed a much better control of the working volume in
      the fermentor from cycle to cycle, compared to the cyclone column, and it was not
      necessary to make periodic corrections.The production of surfactin from B.
      subtilis was achieved without extending the cycle time. The harvested broth at
      the end of each cycle was allowed to remain in a secondary vessel, at ambient
      temperature, before being collected. It is exhaustion of the limiting nutrient
      which causes an increase in dissolved oxygen (DO). At this point, the computer,
      which constantly monitors the DO, triggered the harvesting sequence to end the
      cycle. Thus, the mature culture in the secondary vessel experienced appropriate
      conditions for the production of the secondary metabolite. Meanwhile, the next
      batch of cells was being grown in the primary reactor.The response of a gas
      analyzer on the effluent paralleled that of the DO measurements in the fermentor.
      These data for oxygen and carbon dioxide exhibited less noise than the DO
      readings. Either would be a more reliable parameter for feedback control of the
      SCF because the problem of fouling of the DO probe after extended runs of many
      cycles would be eliminated.

PMID- 18609667
TI  - Effects of rheological properties and mass transfer on plant cell bioreactor
      performance: production of tropane alkaloids.
AB  - Volumetric mass transfer coefficients, K(L)a were measured over an aeration rate
      range from 0.1 to 1.0 vvm in a 1.2-L draft-tube-type airlift bioreactor for
      different Datura stramonium cell concentrations and correlated with superficial
      air velocity and rheological properties of the cell suspension. The measured
      K(L)a values (17-40 h(-1)) for a cell volume fraction of 0.2 (v/v) were
      approximately 2 times higher than those for the highest cell concentrations
      tested (cell volume fraction 0.7-0.8 v/v). Cell suspensions exhibited yield
      stress and pseudoplastic behavior. This behavior was described by the Casson
      model. The estimated yield stress values depended upon cell concentration with an
      exponent of 4.0. An empirical correlation based on the data for plant cell
      suspensions exhibiting yield stress was developed in order to determine aeration
      strategy for the plant cell cultivation in draft-tube-type airlift bioreactors:
      K(L)a = A(U(gr))(0.3(eta(eff))(-0.4). Aeration rates above 1.0 vvm caused a
      significant drop in cell yield and product content. Maximum growth and production
      were obtained at 0.6 vvm aeration. The cell and product yields obtained at 1.7
      vvm were 2.8 times lower than the maximum values (25 g cell DW/L and 73.8 mg
      tropane alkaloid/L). The effects of the increased aeration rates on cell yield
      were also evaluated in terms of Reynolds stress. It was found that there was a
      relation between cell damage and the estimated Reynolds stress. The Reynolds
      stress estimated for the same aeration rate decreased with increasing cell
      concentration, suggesting that cells in the cultures at low cell concentrations
      are subjected to hydrodynamic damage. In the experiments with the cell cultures
      having a cell concentration of 0.3 (v/v), approximately 70% reduction in cell
      concentration was observed when the Reynolds stress was increased from 10 to 50
      dyn/cm(2).

PMID- 18609668
TI  - Real-time compensation of the inner filter effect in high-density bioluminescent
      cultures.
AB  - Bioluminescence has recently become a popular research tool in several fields,
      including medicine, pharmacology, biochemistry, bioprocessing, and environmental
      engineering. Beginning with purely qualitative goals, scientists are now
      targeting more demanding applications where accurate, quantitative interpretation
      of bioluminescence is necessary. Using the recent advances in fiber-optic
      technology, bioluminescence is easily monitored in vivo and in real time.
      However, the convenience of this measurement is often concealing an unsuspected
      problem: the bioluminescence signal might be corrupted by a large error caused by
      the extinction of light by biological cells. Since bioluminescent cultures not
      only emit light but also absorb and scatter it, the measured signal is related in
      a complex, nonlinear, and cell-concentration-dependent manner to the "true"
      bioluminescence. This light extinction effect, known as the "inner filter
      effect," is significant in high-density cultures. Adequate interpretation of the
      bioluminescence signal can be difficult without its correction. Here, we propose
      a real-time algorithm for elimination of the inner filter effect in a bioreactor.
      The algorithm yields the bioluminescence which would be measured if the glowing
      culture was completely transparent. This technique has been successfully applied
      to batch and continuous cultivation of recombinant bioluminescent Escherichia
      coli.

PMID- 18609669
TI  - Affinity-based reversed micellar protein extraction: I. principles and protein
      ligand systems.
AB  - Affinity cosurfactants, consisting of hydrophilic ligands derivatized with
      hydrophobic tails, increase the efficiency of selective protein recoveries using
      reversed micelles by extending the operating range of pH and salt concentration
      over which an extraction can be performed. Three different affinity cosurfactant
      protein pairs have been used to demonstrate the principles of this extractive
      technique: (i) concanavalin A, a lectin, was extracted with the addition of octyl
      glucoside; (ii) natural amphiphiles, such as lecithin, were used to extract
      myelin basic protein, a membrane-associated protein known to recognize and bind
      the phosphatidylcholine headgroup; and (iii) alkyl boronic acids were used to
      extract chymotrypsin. The enhancement in protein transfer correlated with the
      binding strength of the free ligand and protein in aqueous solution. Several
      control studies confirmed the biospecificity of the interactions of protein and
      affinity cosurfactant.

PMID- 18609670
TI  - Affinity-based reversed micellar protein extraction: II. effect of cosurfactant
      tail length.
AB  - The selectivity of protein extraction by reversed micellar solutions can be
      improved by the addition of affinity cosurfactants bearing ligands which bind
      strongly to the target protein. The interactions between cosurfactant and
      protein, as well as the interfacial activity of both the free cosurfactant and
      the protein-cosurfactant complex, were accounted for in a model of the affinity
      partitioning process. The aqueous phase dissociation constant was used to
      describe the protein-ligand interactions. The interfacial partition coefficient
      for several cosurfactant families varied with tail length according to the well
      established hydrophobic effect. Control studies with alkylated chymotrypsin
      showed that when longer hydrophobic tails are irreversibly attached to the
      protein, the protein partitions more strongly to the reversed micellar phase. In
      contrast, for reversible protein-cosurfactant binding, the model predicts a
      maximum in protein uptake when the cosurfactant tail length is varied; the
      decrease at longer tail lengths is due to the lowered aqueous phase concentration
      of affinity cosurfactant, resulting in the formation of fewer protein
      cosurfactant complexes. This behavior was confirmed experimentally.

PMID- 18609671
TI  - Step-fortifications of nutrients in mammalian cell culture.
AB  - A series of high-density media for mammalian cell culture were developed by step
      fortifications of most nutrient components in RPMI-1640 medium. Each medium
      constituting the series was constructed to meet in vitro cell growth limitations.
      Four different cell lines were cultivated in the media series, and their growth
      characteristics were observed. Maximum cell densities varied in the range of 0.4
      to 1.3 x 10(7) cells/mL, depending on cell lines. Cell growth responses to each
      of the media series were analyzed in terms of cell density and cell mass. Step
      increases of cell mass in the range of 1.3 to 3.7 g/L were observed according to
      the step-fortifications of nutrients. Also, the characteristics of each cell line
      were compared in terms of metabolic yields and specific productions of lactic
      acid and ammonium ion. The effect of step-fortifications of nutrients on the
      production of monoclonal antibody was also examined. Apparent differences in
      metabolic characteristics among cell lines were observed. Experimental results
      suggested that the different cell sizes and metabolic characteristics of each
      cell line resulted in cell-line-specific responses to the step-fortifications.
      The significant influence of nutritional fortifications on high-density culture
      of mammalian cells was evaluated.

PMID- 18609672
TI  - Repeated fed-batch culture of hybridoma cells in nutrient-fortified high-density
      medium.
AB  - Long-term high-density cultivation of the hybridoma 2c3.1 was successfully
      carried out in a repeated fed-batch mode using high-density media that were
      constructed to meet in vitro cell growth limitations. The high-density culture
      was possible in a range of 0.5 approximately 1.0 x 10(7) cells/mL in MBRI 40-02
      medium for over 2500 h by the repeated supplementation of the most fortified
      medium, MBRI 40-03, and consequently, distinct enhancement of MAb production was
      achieved. MAb concentrations were maintained around 1 g/L for about 1000 h of the
      process and the maximum MAb concentration was around 1.56 g/L. The result
      supported strongly the fact that the nutritional fortification was the most
      critical factor for high-density cell culture in vitro. The mean chromosome
      number of the hybridoma 2c3.1 was maintained stably for about 1500 h, whereas
      gradual loss of the MAb activity was apparent during the long-term cultivation.

PMID- 18609673
TI  - Adsorption-desorption of recombinant hepatitis B surface antigen (r-HBsAg) from
      P. pastoris on a diatomaceous earth matrix: Optimization of parameters for
      purification.
AB  - Recombinant hepatitis B surface antigen (r-HBsAg) produced in yeast is adsorbed
      on a diatomaceous earth matrix for purification purposes. A pH dependence in the
      adsorption-elution behavior was found. The capacity of celite (Hyflo Super Cei)
      for adsorbing r-HBsAg increased with decreasing pH. Nonspecific proteins were
      also adsorbed, but a low pH dependence was found. Elution from the matrix was
      performed using a basic pH buffer, in which r-HBsAg is more specifically
      adsorbed/desorbed than contaminant proteins, permitting the purification of the r
      HBsAg. A pH of 4.0 was used for adsorption and pH 8.2 was used for desorption.
      The described protocol allows a purification factor between three- and fivefold
      with respect to contaminant proteins and sixfold with respect to contaminant DNA.
      Finally, the adsorption step was successfully scaled-up for production purposes.

PMID- 18609674
TI  - Estimation of melting curves from enzymatic activity-temperature profiles.
AB  - Measuring the reversible thermal unfolding of enzymes is valuable for quantifying
      the effects of environmental factors on the thermodynamic stability of proteins.
      The thermal unfolding behavior of enzymes is typically studied using calorimetry
      or optical techniques such as circular dichroism, fluorescence, or light
      scattering. These techniques often have practical limitations and usually require
      the protein to be electrophoretically pure. An alternative technique for
      analyzing the thermodynamic stability of enzymes is to estimate the melting curve
      from temperature-activity data. This technique does not require
      electrophoretically pure enzyme, provided the sample does not have competing
      enzymatic activities or proteins which can affect enzyme stability (e.g.,
      proteases). Moreover, small amounts of contaminant proteins should not affect the
      results as long as enzymatic assays are performed at low protein concentrations
      where nonspecific protein-protein interactions are negligible. To illustrate this
      technique, the melting curve for beta-galactosidase from Escherichia coli in the
      presence of 1 mM EDTA, and the shift caused by adding 1 mM Mg(+2), were
      calculated from activity-temperature data. Melting temperatures predicted from
      activity-temperature data compared closely with those obtained using other
      techniques. Application of this analysis to multisubstrate enzymes is illustrated
      by estimating the melting profiles for partially purified hydrogenases from
      several thermophilic Methanococcii. Limitations and important considerations for
      estimating melting profiles from activity-temperature data are discussed.

PMID- 18609675
TI  - Design of a biomedical reactor for plasma low-density lipoprotein removal.
AB  - The purpose of this study was to design a biomedical reactor that reduces plasma
      cholesterol when incorporated in an in vivo extracorporeal system. Phospholipase
      A(2), immobilized onto Agarose beads and housed inside the bioreactor, modifies
      plasma low density lipoprotein (LDL) into a form that is rapidly removed from
      circulation. In a packed bed reactor, the enzymatic conversion of LDL to the
      modified form (with plasma taken from hypercholesterolemic New Zealand white
      rabbits) was relatively low, 25% +/- 6 for a single pass of plasma through the
      reactor. An extended bed reactor, a hybrid of fluidized and packed bed reactors,
      was then developed to increase the conversion. This reactor displays a single
      pass conversion of 60% +/- 5 under optimal flow conditions. An evaluation of the
      flow rate through the reactor indicates that the system is limited by external
      mass transfer when employed under in vivo conditions. In addition, this system
      requires blood separation before the enzyme modification, which complicates the
      circuit control. Therefore, a new system was designed for in vivo use with
      rabbits. The resulting design, called the plasma separator reactor (PSR),
      combines plasma separation and enzymatic conversion in a single chamber. The PSR
      has three advantages over other studied systems: improved external mass transfer
      conditions, easy controllability, and simple set-up procedures. Single pass
      conversion reached 52% +/- 12 in suboptimal flow under simulated in vivo
      conditions. This reactor was also tested in vivo with hypercholesterolemic New
      Zealand white rabbits. A continuous conversion of up to 80% +/- 6 of rabbit
      plasma phospholipids was observed during 90 min of blood circulation (5 mL/min).
      The decrease in total plasma cholesterol reached a level of 60% of the initial
      value and was observed to be a function of the bioreactor enzyme activity.

PMID- 18609676
TI  - Risk for colorectal cancer in ulcerative colitis: changes, causes and management
      strategies.
AB  - The risk of colorectal cancer for any patient with ulcerative colitis is known to
      be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18%
      after 30 years of disease. Risk factors for cancer include extent and duration of
      ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic
      colorectal cancer, severity of histologic bowel inflammation, and in some
      studies, young age at onset of colitis. In this review, the authors discuss
      recent epidemiological trends and causes for the observed changes. Population
      based studies published within the past 5 years suggest that this risk has
      decreased over time, despite the low frequency of colectomies. The crude annual
      incidence rate of colorectal cancer in ulcerative colitis ranges from
      approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact
      mechanism for this change is unknown; it may partly be explained by the more
      widespread use of maintenance therapy and surveillance colonoscopy.

PMID- 18609677
TI  - IgG4-related sclerosing disease.
AB  - Based on histological and immunohistochemical examination of various organs of
      patients with autoimmune pancreatitis (AIP), a novel clinicopathological entity
      of IgG4-related sclerosing disease has been proposed. This is a systemic disease
      that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte
      infiltration of various organs. Clinical manifestations are apparent in the
      pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung,
      and prostate, in which tissue fibrosis with obliterative phlebitis is
      pathologically induced. AIP is not simply pancreatitis but, in fact, is a
      pancreatic disease indicative of IgG4-related sclerosing diseases. This disease
      includes AIP, sclerosing cholangitis, cholecystitis, sialadenitis,
      retroperitoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia,
      prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most
      IgG4-related sclerosing diseases have been found to be associated with AIP, but
      also those without pancreatic involvement have been reported. In some cases, only
      one or two organs are clinically involved, while in others, three or four organs
      are affected. The disease occurs predominantly in older men and responds well to
      steroid therapy. Serum IgG4 levels and immunostaining with anti-IgG4 antibody are
      useful in making the diagnosis. Since malignant tumors are frequently suspected
      on initial presentation, IgG4-related sclerosing disease should be considered in
      the differential diagnosis to avoid unnecessary surgery.

PMID- 18609679
TI  - Gaucher disease: new developments in treatment and etiology.
AB  - Gaucher disease (GD) is an autosomal recessive disease which if undiagnosed or
      diagnosed late results in devastating complications. Because of the heterozygous
      nature of GD, there is a wide spectrum of clinical presentation. Clinicians
      should be aware of this rare but potentially treatable disease in patients who
      present with unexplained organomegaly, anemia, massive splenomegaly, ascites and
      even cirrhosis of unknown origin. The treatment options for adult type GD include
      enzyme replacement treatment (ERT) and substrate reduction treatment (SRT)
      depending on the status of the patient. Future treatment options are gene therapy
      and "smart molecules" which provide specific cure and additional treatment
      options. In this review, we present the key issues about GD and new developments
      that gastroenterologists should be aware of.

PMID- 18609680
TI  - Primary sclerosing cholangitis--what is the difference between east and west?
AB  - Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver
      disease characterized by inflammation and fibrotic obliteration of the hepatic
      biliary tree. It is commonly associated with inflammatory bowel disease (IBD). A
      number of complications can occur which require special consideration, the most
      important of which is the development of cholangiocellular carcinoma (CCC).
      Unfortunately, no medical therapy is currently available for the underlying liver
      disease. Liver transplantation is an effective, life-extending option for
      patients with advanced PSC. Geographical variations between East and West include
      a second peak for age with a lower association with IBD in a Japanese population
      and female predominance in a lone study from Turkey. The clinical and biochemical
      Mayo criteria may not be universally applicable, as different patients show
      variations regarding the initial presentation and natural course of the disease.
      Directing research towards explaining these geographical differences and
      understanding the pathogenesis of PSC is required in order to develop better
      therapies for this devastating disease.

PMID- 18609678
TI  - Evolving management of colorectal cancer.
AB  - This article reviews recent advances in surgical techniques and adjuvant
      therapies for colorectal cancer, including total mesorectal excision, the
      resection of liver and lung metastasis and advances in chemoradiation and
      foreshadows some interventions that may lie just beyond the frontier. In
      particular, little is known about the intracellular and extracellular cascades
      that may influence colorectal cancer cell adhesion and metastasis. Although the
      phosphorylation of focal adhesion kinases and focal adhesion associated proteins
      in response to integrin-mediated cell matrix binding ("outside in integrin
      signaling") is well described, the stimulation of cell adhesion by intracellular
      signals activated by pressure prior to adhesion represents a different signal
      paradigm. However, several studies have suggested that increased pressure and
      shear stress activate cancer cell adhesion. Further studies of the pathways that
      regulate integrin-driven cancer cell adhesion may identify ways to disrupt these
      signals or block integrin-mediated adhesion so that adhesion and eventual
      metastasis can be prevented in the future.

PMID- 18609681
TI  - Lithium inhibits proliferation of human esophageal cancer cell line Eca-109 by
      inducing a G2/M cell cycle arrest.
AB  - AIM: To investigate the effect of lithium on proliferation of esophageal cancer
      (EC) cells and its preliminary mechanisms. METHODS: Eca-109 cells were treated
      with lithium chloride, a highly selective inhibitor of glycogen synthase kinase
      3beta (GSK-3beta), at different concentrations (2-30 mmol/L) and time points (0,
      2, 4, 6 and 24 h). Cell proliferative ability was evaluated by 3-(4,5
      Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, and cell
      cycle distribution was examined by flow cytometry. Expressions of p-GSK-3beta,
      beta-catenin, cyclin B1, cdc2 and cyclin D1 protein were detected by Western
      blotting, and the subcellular localization of beta-catenin was determined by
      immunofluorescence. The mRNA level of cyclin B1 was detected by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: Lithium could inhibit
      the proliferation of Eca-109 cells. Lithium at a concentration of 20 mmol/L
      lithium for 24 h produced obvious changes in the distribution of cell cycle, and
      increased the number of cells in G(2)/M phase (P<0.05 vs control group). Western
      blotting showed that lithium inhibited GSK-3beta by Ser-9 phosphorylation and
      stabilized free beta-catenin in the cytoplasm. Immunofluorescence further
      confirmed that free beta-catenin actively translocated to the nucleus. Moreover,
      lithium slightly elevated cyclin D1 protein expression, whereas lowered the
      cyclin B1 expression after 24 h lithium exposure and no obvious change was
      observed for cdc2 protein. CONCLUSION: Lithium can inhibit the proliferation of
      human esophageal cancer cell line Eca-109 by inducing a G(2)/M cell cycle arrest,
      which is mainly mediated through the inhibition of lithium-sensitive molecule,
      GSK-3beta, and reduction of cyclin B1 expression.

PMID- 18609683
TI  - Characteristics of liver on magnetic resonance diffusion-weighted imaging:
      dynamic and image pathological investigation in rabbit liver VX-2 tumor model.
AB  - AIM: To investigate dynamical and image pathological characteristics of the liver
      on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2
      tumor model. METHODS: Forty New Zealand rabbits were included in the study and VX
      2 tumor piece was implanted intrahepatically. Fifteen animals received two
      intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1-
      and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th
      and the 14th d after implantation and DWI was conducted, respectively on the 21st
      d. Ten VX-2 tumor samples were studied pathologically. RESULTS: The rate of lump
      detected by DWI, T1WI and T2WI was 78.7%, 10.7% and 53.5% (c2=32.61, P<0.001) on
      the 7th d after implantation and 95.8%, 54.3% and 82.9% (c2=21.50, P<0.001) on
      the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on
      the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not
      decrease on the 7th d after implantation, most of them slowly growing during the
      week following implantation without significant cell dying within the tumor. VX-2
      tumors grew increasingly within 14 d after implantation but the signal of most VX
      2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors
      decreased obscurely or slightly because tumor necrosis was still not obvious. On
      the 21st d after implantation, the signal of most VX-2 tumors on DWI or on the
      map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor
      necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a
      high signal on DWI and a low signal on the map of ADC. The areas of dead cells or
      necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high
      signals on the map of ADC but they manifested high signals on DWI and on the map
      of ADC at the same time when the areas of necrotic tumor became liquefied or
      cystic. The border of tumors on DWI appeared gradually distinct and internal
      signals of tumor became progressively uneven. CONCLUSION: The manifestations of
      viable, necrotic and liquefied or cystic areas in VX-2 tumors on DWI are typical
      and DWI is of significant and potential values in clinical application in both
      the early detection and diagnosis of liver tumors.

PMID- 18609682
TI  - Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines
      in vitro and xenografted sarcoma 180 in Kunming mice.
AB  - AIM: To investigate the anti-tumor effect of Chinese medicine Gecko on human
      esophageal carcinoma cell lines and xenografted sarcoma 180 in Kunming mice and
      its mechanism. METHODS: The serum pharmacological method was used in vitro. The
      growth rates of the human esophageal carcinoma cells (EC9706 or EC1) were
      measured by a modified 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. The transplanted tumor model of the mouse S180 sarcoma was
      established. Fifty mice were randomly divided into five groups (n=10). Three
      Gecko groups were treated respectively with oral administration of Gecko powder
      at a daily dose of 13.5 g/kg, 9 g/kg, and 4.5 g/kg. The negative group (NS group)
      was treated with oral administration of an equal volume of saline and the
      positive group (CTX group) was treated with 100 mg/kg Cytoxan by intraperitoneal
      injection at the first day. After 2 wk of treatment, the anti-tumor activity was
      evaluated by tumor tissue weighing. The impact on immune organ was detected based
      on the thymus index, spleen index, phagocytic rate and phagocytic index. The
      protein expression of vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) were detected by immunohistochemistry. The cell
      apoptotic rate was detected by terminal deoxynucleotidyl transferase (TdT)
      mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The OD value in each
      group treated with Gecko after 72 h was reduced significantly in EC9706 and in
      EC1. The tumor weight in each group of Gecko was decreased significantly (1.087+/
      0.249 vs 2.167+/-0.592; 1.021+/-0.288 vs 2.167+/-0.592; 1.234+/-0.331 vs 2.167+/
      0.592; P<0.01, respectively). However, the thymus index and Spleen index of mice
      in Gecko groups had no significant difference compared with the NS group. The
      immunoreactive score of VEGF and bFGF protein expression of each Gecko group by
      immunohistochemical staining were lowered significantly. The apoptosis index (AI)
      of each group was increased progressively with increase of dose of Gecko by
      TUNEL. CONCLUSION: Gecko has anti-tumor effects in vitro and in vivo; induction
      of tumor cell apoptosis and the down-regulation of protein expression of VEGF and
      bFGF may be contributed to anti-tumor effects of Gecko.

PMID- 18609684
TI  - Value of contrast-enhanced intraoperative ultrasound for cirrhotic patients with
      hepatocellular carcinoma: a report of 20 cases.
AB  - AIM: To assess the clinical value of contrast-enhanced intraoperative ultrasound
      (CE-IOUS) as a novel tool in partial hepatectomy for cirrhotic patients with
      hepatocellular carcinoma (HCC). METHODS: From January 2007 to September 2007, a
      total of 20 consecutive cirrhotic patients with HCC scheduled to undergo partial
      hepatectomy were studied. Preoperative contrast enhanced computer tomography (CT)
      and/or magnetic resonance (MR) scans were performed within 1-2 wk before
      operation. Intraoperative ultrasound (IOUS) and CE-IOUS were carried out after
      mobilization of the liver. Lesions on precontrast and postcontrast scans were
      counted and mapped. CE-IOUS was performed with intravenous injection of
      ultrasound contrast agents SonoVue (Bracco Imaging, Milan, Italy). Arterial,
      portal and late phases of contrast enhancement were recorded and analyzed.
      Nodules showing arterial phase hyper-enhancing and/or hypo-enhancing in late
      parenchymal phase were considered malignant and removed surgically. Ultrasound
      guided biopsy and ethanol ablation would be an option if the nodule could not be
      removed surgically. Newly detected nodules on IOUS showing iso-enhancement in
      both arterial and late phases were considered benign. These nodules were either
      removed surgically if they were close to the main lesion or followed by
      examinations of alpha-fetoprotein (AFP) level and ultrasound and/or CT/MR every 3
      mo. RESULTS: IOUS found 41 nodules in total, among which 17 (41.46%) were newly
      detected compared to preoperative imaging. Thirty-three nodules were diagnosed
      malignant by CE-IOUS, including one missed by IOUS. The sensitivity and
      specificity of CE-IOUS on detecting HCC nodules are 100% (33/33 and 100% (9/9),
      respectively. Nine nodules were considered benign by CE-IOUS, four was confirmed
      at histology and five by follow-up. CE-IOUS changed the surgical strategy in 35%
      (7/20) of patients and avoid unnecessary intervention in 30% (6/20) of patients.
      CONCLUSION: CE-IOUS is a useful means to characterize the nodules detected by
      IOUS in cirrhotic liver, to find isoechoic HCC nodules which can not be shown on
      IOUS and to improve the accuracy of conventional IOUS, thus it can be used as an
      essential tool in the surgical treatment of cirrhotic patients with HCC.

PMID- 18609685
TI  - How good is endoscopic ultrasound for TNM staging of gastric cancers? A meta
      analysis and systematic review.
AB  - AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) for staging of
      gastric cancers. METHODS: Only EUS studies confirmed by surgery were selected.
      Only studies from which a 2 x 2 table could be constructed for true positive,
      false negative, false positive and true negative values were included. Articles
      were searched in Medline, Pubmed, Ovid journals, Cumulative index for nursing and
      allied health literature, International pharmaceutical abstracts, old Medline,
      Medline nonindexed citations, and Cochrane control trial registry. Two reviewers
      independently searched and extracted data. The differences were resolved by
      mutual agreement. 2 x 2 tables were constructed with the data extracted from each
      study. Meta-analysis for the accuracy of EUS was analyzed by calculating pooled
      estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds
      ratio. Pooling was conducted by both the Mantel-Haenszel method (fixed effects
      model) and DerSimonian Laird method (random effects model). The heterogeneity of
      studies was tested using Cochran's Q test based upon inverse variance weights.
      RESULTS: Initial search identified 1620 reference articles and of these, 376
      relevant articles were selected and reviewed. Twenty-two studies (n=1896) which
      met the inclusion criteria were included in this analysis. Pooled sensitivity of
      T1 was 88.1% (95% CI: 84.5-91.1) and T2 was 82.3% (95% CI: 78.2-86.0). For T3,
      pooled sensitivity was 89.7% (95% CI: 87.1-92.0). T4 had a pooled sensitivity of
      99.2% (95% CI: 97.1-99.9). For nodal staging, the pooled sensitivity for N1 was
      58.2% (95% CI: 53.5-62.8) and N2 was 64.9% (95% CI: 60.8-68.8). Pooled
      sensitivity to diagnose distant metastasis was 73.2% (95% CI: 63.2-81.7). The P
      for chi-squared heterogeneity for all the pooled accuracy estimates was >0.10.
      CONCLUSION: EUS results are more accurate with advanced disease than early
      disease. If EUS diagnoses advanced disease, such as T4 disease, the patient is
      500 times more likely to have true anatomic stage of T4 disease.

PMID- 18609686
TI  - Is the pain in chronic pancreatitis of neuropathic origin? Support from EEG
      studies during experimental pain.
AB  - AIM: To prove the hypothesis that patients with chronic pancreatitis would show
      increased theta activity during painful visceral stimulation. METHODS: Eight
      patients and 12 healthy controls underwent an experiment where the esophagus was
      electrically stimulated at the pain threshold using a nasal endoscope. The
      electroencephalogram (EEG) was recorded from 64 surface electrodes and
      "topographic matching pursuit" was used to extract the EEG information in the
      early brain activation after stimulation. RESULTS: A major difference between
      controls and patients were seen in delta and theta bands, whereas there were only
      minor differences in other frequency bands. In the theta band, the patients
      showed higher activity than controls persisting throughout the 450 ms of analysis
      with synchronous brain activation between the channels. The main theta components
      oscillated with 4.4 Hz in the patients and 5.5 Hz in the controls. The energy in
      the delta (0.5-3.5 Hz) band was higher in the controls, whereas the patients only
      showed scattered activity in this band. CONCLUSION: The differences in the theta
      band indicate that neuropathic pain mechanisms are involved in chronic
      pancreatitis. This has important implications for the understanding and treatment
      of pain in these patients, which should be directed against drugs with effects on
      neuropathic pain disorders.

PMID- 18609687
TI  - Inflammatory bowel disease in rats: bacterial and chemical interaction.
AB  - AIM: To develop a novel model of colitis in rats, using a combination of
      iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the
      pathophysiologic processes implicated in the development of ulcerative colitis
      (UC). METHODS: Male Sprague-Dawley rats (n = 158) were inoculated intrarectally
      on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b)
      100 microL of 6% iodoacetamide (IA) in 1% MC, (c) 200 microL containing 4 x 10(8)
      colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by
      bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was
      divided into two subgroups; the inoculation was stopped for one subgroup and the
      other subgroup continued with biweekly inoculation until the end of the
      experiment. Colitis was evaluated by the clinical course of the disease, the
      macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and
      by TNF-alpha gene expression. RESULTS: Findings indicative of UC were seen in the
      combined treatment (IA + B) as well as the IA continued treatment groups: the
      animals showed slow rate of increase in body weight, diarrhea, bloody stools,
      high colonic ulcer score, as well as histological alterations characteristic of
      UC, with an extensive inflammatory reaction. During the course of the experiment,
      the MPO activity was consistently elevated and the TNF-alpha gene expression was
      upregulated compared to the control animals. CONCLUSION: The experimental
      ulcerative colitis model used in the present study resembles, to a great extent,
      the human disease. It is reproducible with characteristics indicative of
      chronicity.

PMID- 18609688
TI  - Composition of inflammatory infiltrate and its correlation with HBV/HCV antigen
      expression.
AB  - AIM: To study the composition of liver inflammatory infiltrate in biopsy material
      from patients chronically infected with hepatotropic viruses and to evaluate the
      correlation of inflammatory infiltrate with hepatitis B virus (HBV) and hepatitis
      C virus (HCV) viral antigen expression in chronic B and C hepatitis. METHODS: The
      phenotype of inflammatory cells was evaluated by the EnVision system, using a
      panel of monoclonal antibodies. HBV and HCV antigens were detected with the use
      of monoclonal anti-HBs, polyclonal anti-HBc and anti-HCV antibodies,
      respectively. RESULTS: The cellular composition of liver inflammatory infiltrate
      was similar in the patients with B and C hepatitis: approximately 50%-60% of
      cells were T helper lymphocytes. Approximately 25% were T cytotoxic lymphocytes;
      B lymphocytes comprised 15% of inflammatory infiltrate; other cells, including
      NK, totalled 10%. Expression of HLA antigens paralleled inflammatory activity.
      Portal lymphadenoplasia was found more often in hepatitis C (54.5%) than in
      hepatitis B (30.6%). Expression of HBcAg was found more often in chronic B
      hepatitis of moderate or severe activity. Overall inflammatory activity in HBV
      infected cases did not correlate with the intensity of HBsAg expression in
      hepatocytes. Inflammatory infiltrates accompanied the focal expression of HCV
      antigens. A direct correlation between antigen expression and inflammatory
      reaction in situ was noted more often in hepatitis C than B. CONCLUSION:
      Irrespective of the etiology and activity of hepatitis, components of the
      inflammatory infiltrate in liver were similar. Overall inflammatory activity did
      not correlate with the expression of HBsAg and HCVAg; HBcAg expression, however,
      accompanied chronic hepatitis B of moderate and severe activity.

PMID- 18609689
TI  - Acute upper gastrointestinal bleeding in octogenarians: clinical outcome and
      factors related to mortality.
AB  - AIM: To evaluate the aetiology, clinical outcome and factors related to mortality
      of acute upper gastrointestinal bleeding (AUGIB) in octogenarians. METHODS: We
      reviewed the records of all patients over 65 years old who were hospitalised with
      AUGIB in two hospitals from January 2006 to December of 2006. Patients were
      divided into two groups: Group A (65-80 years old) and Group B (>80 years old).
      RESULTS: Four hundred and sixteen patients over 65 years of age were hospitalized
      because of AUGIB. Group A included 269 patients and Group B 147 patients. Co
      morbidity was more common in octogenarians (P=0.04). The main cause of bleeding
      was peptic ulcer in both groups. Rebleeding and emergency surgery were uncommon
      in octogenarians and not different from those in younger patients. In-hospital
      complications were more common in octogenarians (P=0.05) and more patients died
      in the group of octogenarians compared to the younger age group (P=0.02).
      Inability to perform endoscopic examination (P=0.002), presence of high risk for
      rebleeding stigmata (P=0.004), urea on admission (P=0.036), rebleeding (P=0.004)
      and presence of severe co-morbidity (P<0.0001) were related to mortality. In
      multivariate analysis, only the presence of severe co-morbidity was independently
      related to mortality (P=0.032). CONCLUSION: While rebleeding and emergency
      surgery rates are relatively low in octogenarians with AUGIB, the presence of
      severe co-morbidity is the main factor of adverse outcome.

PMID- 18609690
TI  - Successful outcomes of EMR-L with 3D-EUS for rectal carcinoids compared with
      historical controls.
AB  - AIM: To assess the results of endoscopic mucosal resection with a ligation device
      (EMR-L) combined with three dimensional endoscopic ultrasonography (3D-EUS) using
      an ultrasonic probe for rectal carcinoids. In addition, diagnosis of the depth
      and size of lesions by EUS was evaluated. METHODS: Between January 2003 and March
      2007, 20 patients underwent EMR-L with 3D-EUS using an ultrasonic probe (group
      A). 3D-EUS was combined with EMR-L at the time of injection of sterile
      physiological saline into the submucosal layer. For comparison, 14 rectal
      carcinoids that had been treated by EMR-L without 3D-EUS between April 1998 and
      December 2002 were evaluated as historical controls (group B). EUS was conducted
      for all of the patients before treatment to evaluate tumor diameter and depth of
      invasion. The percentage of complete resection and the vertical resection margin
      were compared between the two groups. RESULTS: The depth of invasion upon
      histopathological examination was in complete agreement with the pre-operative
      findings by EUS. The tumor diameter determined by EUS approximated that found in
      the tissue samples. There were no significant differences in the gender, tumor
      sites or tumor diameters between the two groups. The rate of complete resection
      for groups A and B was 100% and 71%, respectively (P<0.05). The vertical
      resection margin of group A was longer than that of group B. CONCLUSION: EMR-L is
      effective as an endoscopic treatment for rectal carcinoids. In combination with
      3D-EUS, safe and complete resection is further assured.

PMID- 18609691
TI  - Rebamipide enema therapy for left-sided ischemic colitis patients accompanied by
      ulcers: open label study.
AB  - AIM: To attempt rectal administration of rebamipide in the treatment of ischemic
      colitis patients with ulcers, and evaluate its effects. METHODS: We compared 9
      ischemic colitis patients (2 men, 7 women) with ulcers treated by bowel rest only
      from 2000 to 2005 (conventional therapy group), with 6 patients (2 men, 4 women)
      treated by rebamipide enema therapy in 2006 (rebamipide enema therapy group) and
      analyzed the mean duration of fasting and hospitalization, degree of ulcer
      healing, and decrease in WBC count for the two groups. RESULTS: The mean duration
      of fasting and hospitalization were 2.7+/-1.8 d and 9.2+/-1.5 d in the rebamipide
      group and 7.9+/-4.1 d and 17.9+/-6.8 d in the control group, respectively, and
      significantly reduced in the rebamipide group (t= -2.915; P=0.0121 and t= -3.054;
      P=0.0092). As for the degree of ulcer healing at 7 d after admission, the ulcer
      score was reduced by 3.5+/-0.5 (points) in the rebamipide group and 2.8+/-0.5
      (points) in the control group (t=1.975; P=0.0797), while the decrease in WBC
      count was 120.0+/-55.8 (x 10(2)/microL) in the rebamipide group and 85.9+/-56.8
      (x 10(2)/microL) in the control group (t=1.006; P=0.3360). CONCLUSION: In left
      sided ischemic colitis patients with ulcers, rebamipide enema therapy
      significantly reduced the duration of fasting and hospitalization, recommending
      its use as a new and effective therapeutic alternative.

PMID- 18609692
TI  - Ultrasonically activated scalpel versus monopolar electrocautery shovel in
      laparoscopic total mesorectal excision for rectal cancer.
AB  - AIM: To investigate the feasibility and safety of monopolar electrocautery shovel
      (ES) in laparoscopic total mesorectal excision (TME) with anal sphincter
      preservation for rectal cancer in order to reduce the cost of the laparoscopic
      operation, and to compare ES with the ultrasonically activated scalpel (US).
      METHODS: Forty patients with rectal cancer, who underwent laparoscopic TME with
      anal sphincter preservation from June 2005 to June 2007, were randomly divided
      into ultrasonic scalpel group and monopolar ES group, prospectively. White blood
      cells (WBC) were measured before and after operation, operative time, blood loss,
      pelvic volume of drainage, time of anal exhaust, visual analogue scales (VAS) and
      surgery-related complications were recorded. RESULTS: All the operations were
      successful; no one was converted to open procedure. No significant differences
      were observed in terms of preoperative and postoperative d 1 and d 3 WBC counts
      (P=0.493, P=0.375, P=0.559), operation time (P=0.235), blood loss (P=0.296), anal
      exhaust time (P=0.431), pelvic drainage volume and VAS in postoperative d 1
      (P=0.431, P=0.426) and d 3 (P=0.844, P=0.617) between ES group and US group. The
      occurrence of surgery-related complications such as anastomotic leakage and wound
      infection was the same in the two groups. CONCLUSION: ES is a safe and feasible
      tool as same as US used in laparoscopic TME with anal sphincter preservation for
      rectal cancer on the basis of the skillful laparoscopic technique and the
      complete understanding of laparoscopic pelvic anatomy. Application of ES can not
      only reduce the operation costs but also benefit the popularization of
      laparoscopic operation for rectal cancer patients.

PMID- 18609693
TI  - Microsatellite alterations in phenotypically normal esophageal squamous
      epithelium and metaplasia-dysplasia-adenocarcinoma sequence.
AB  - AIM: To investigate the microsatellite alterations in phenotypically normal
      esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence.
      METHODS: Forty-one specimens were obtained from esophageal cancer (EC) patients.
      Histopathological assessment identified 23 squamous cell carcinomas (SCC) and 18
      adenocarcinomas (ADC), including only 8 ADC with Barrett esophageal columnar
      epithelium (metaplasia) and dysplasia adjacent to ADC. Paraffin-embedded normal
      squamous epithelium, Barrett esophageal columnar epithelium (metaplasia),
      dysplasia and esophageal tumor tissues were dissected from the surrounding
      tissues under microscopic guidance. DNA was extracted using proteinase K
      digestion buffer, and DNA was diluted at 1:100, 1:1000, 1:5000, 1:10000 and
      1:50000, respectively. Seven microsatellite markers (D2S123, D3S1616, D3S1300,
      D5S346, D17S787, D18S58 and BATRII loci) were used in this study. Un-dilution and
      dilution polymerase chain reactions (PCR) were performed, and microsatellite
      analysis was carried out. RESULTS: No statistically significant difference was
      found in microsatellite instability (MSI) and loss of heterozygosity (LOH) of un
      diluted DNA between SCC and ADC. The levels of MSI and LOH were high in the
      metaplasia-dysplasia-adenocarcinoma sequence of diluted DNA. The more the diluted
      DNA was, the higher the rates of MSI and LOH were at the above 7 loci, especially
      at D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci. CONCLUSION: The sequence of
      metaplasia-dysplasia-adenocarcinoma is associated with microsatellite
      alterations, including MSI and LOH. The MSI and LOH may be the early genetic
      events during esophageal carcinogenesis, and genetic alterations at the D3S1616,
      D5S346 and D3S123 loci may play a role in the progress of microsatellite
      alterations.

PMID- 18609694
TI  - Sphincter of Oddi hypomotility and its relationship with duodenal-biliary reflux,
      plasma motilin and serum gastrin.
AB  - AIM: To detect whether patients with a T tube after cholecystectomy and
      choledochotomy have duodenal-biliary reflux by measuring the radioactivity of
      Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and
      whether the patients with duodenal-biliary reflux have sphincter of Oddi
      hypomotility, by measuring the level of plasma and serum gastrin of the patients.
      Finally to if there is close relationship among sphincter of Oddi hypomotility,
      duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five
      patients with a T tube after cholecystectomy and choledochotomy were divided into
      reflux group and control group. The level of plasma and serum gastrin of the
      patients and of 12 healthy volunteers were measured by radioimmunoassay. Thirty
      four were selected randomly to undergo choledochoscope manometry. Sphincter of
      Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF),
      duration of contractions (SOD), duodenal pressure (DP) and common bile duct
      pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were
      detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group
      were much lower than the control group (t=5.254, 3.438 and 3.527, P<0.001). SOD
      of the reflux group was shorter than the control group (t=2.049, P<0.05). The
      level of serum gastrin and plasma motilin of the reflux group was much lower than
      the control group (t= -2.230 and -2.235, P<0.05). There was positive correlation
      between the level of plasma motilin and SOBP and between the level of serum
      gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube
      after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of
      them have sphincter of Oddi hypomotility and the decreased level of plasma
      motilin and serum gastrin. The disorder of gastrointestinal hormone secretion may
      result in sphincter of Oddi dysfunction. There is a close relationship between
      sphincter of Oddi hypomotility and duodenal-biliary reflux.

PMID- 18609695
TI  - Changes of serum p53 antibodies and clinical significance of radiotherapy for
      esophageal squamous cell carcinoma.
AB  - AIM: To explore the relationship between serum p53 antibodies (p53-Abs) and
      clinicopathological characteristics and therapeutic effect in patients with
      esophageal carcinoma (EC), and to investigate sequential changing regularity of
      serum p53-Abs after radiotherapy. METHODS: The serum p53-Ab levels were detected
      in 46 EC patients and 30 healthy adults by enzyme linked immunosorbent assay
      (ELISA). The blood samples were collected on the day before radiotherapy and on
      the administration of an irradiation dose of 20 Gy/10 f/12 d, 40 Gy/20 f/24 d and
      60 Gy/30 f/36 d after radiotherapy. RESULTS: The level and positive rate of serum
      p53-Abs in EC patients were significantly higher than those in normal individuals
      (P<0.05). Serum anti-p53 antibodies were positive in 18 of 46 EC patients
      (39.1%). The positive rate of p53-Abs in EC was related to histological grade,
      disease stage and lymph node metastasis (P<0.05), but it was not significantly
      related to sex, age and to the size and site of tumor. The level and positive
      rate of p53-Abs had significant differences between before radiotherapy and after
      administration of an irradiation dose of 40 Gy/20 f/24 d and 60 Gy/30 f/36 d
      (P<0.05 or P<0.01). The positive rate of p53-Abs in EC patients with effect was
      significantly lower than that in those without effect after radiotherapy
      (P<0.0001). CONCLUSION: Detection of serum p53-Abs is helpful to the diagnosis of
      esophageal carcinoma. Monitoring for sequential change of serum p53-Abs before
      and after radiotherapy in patients with esophageal carcinoma is also useful to
      evaluate the response to the treatment and prognosis of the patients.

PMID- 18609696
TI  - Takayasu's arteritis following Crohn's disease in a young woman: any evidence for
      a common pathogenesis?
AB  - Takayasu's arteritis and Crohn's disease are chronic inflammatory diseases of
      uncertain aetiology. They rarely occur together, with only twenty nine cases of
      co-existent Takayasu's arteritis and Crohn's disease reported in the literature.
      In 88% of these cases, Takayasu's arteritis was diagnosed simultaneously or
      following a diagnosis of Crohn's disease. We present a case of a young Caucasian
      medical student, incidentally found to have bilateral carotid bruits on
      auscultation by a colleague. Magnetic resonance angiography revealed stenoses of
      the common carotid arteries with established collaterals, and a diagnosis of Type
      1 Takayasu's arteritis was made. An 18(F)-fluorodeoxyglucose positron emission
      tomography scan revealed no active disease. Nine months later, she presented with
      a short history of abdominal pain, vomiting and abdominal distension. Barium
      follow-through and computer tomography revealed a terminal ileal stricture and
      proximal small bowel dilation. An extended right hemicoloectomy was performed and
      histopathology supported a diagnosis of Crohn's disease. This case report is
      presented with a particular focus on the temporal relationship between these two
      disease processes and explores whether their concurrence is more than just co
      incidence.

PMID- 18609697
TI  - Gastric arterio-venous malformation emerging from splenic artery.
AB  - In this case report, we present a patient who suffered from gastrointestinal
      bleeding. The bleeding source was a gastric arterio-venous malformation emerging
      from the splenic artery. Attempts to stop the bleeding failed and therapeutic
      angiography succeeded in occluding the vessel. A search at the literature has not
      yielded any other case report describing this anatomical anomaly.

PMID- 18609698
TI  - Non-Hodgkin lymphoma as a cause of obstructive jaundice with simultaneous
      extrahepatic portal vein obstruction: a case report.
AB  - Non-Hodgkin lymphoma is a rare cause of biliary obstruction. To the best of our
      knowledge, non-Hodgkin lymphoma in the peripancreatic region causing obstructive
      jaundice with simultaneous portal vein (PV) invasion has not yet been reported.
      We present a 50-year-old patient with obstructive jaundice whose extrahepatic
      portal vein was obstructed by the invasion of a peripancreatic non-Hodgkin
      lymphoma. The patient denied any other symptoms such as recurrent fever, night
      sweat and loss of body weight. Computed tomography (CT) revealed a 10 cm mass in
      the retroperitoneal space behind the head of the pancreas causing obstruction of
      the distal bile duct and the PV. A pylorus-preserving pancreaticoduodenectomy
      combined with a PV resection was performed. The PV was reconstructed using an
      autologous right internal jugular vein graft. The resected specimen showed
      endoluminal invasion of both the bile duct and the PV. Histological examination
      showed the mass consisting of diffuse sheets of large malignant lymphoid cells.
      These cells were positive for CD20 and CD79a, partially positive for CD10, and
      negative for CD3, CD4, CD5, CD8 and CD30. The pathologic diagnosis was diffuse
      large B-cell type non-Hodgkin lymphoma and the patient was transferred to the
      Department of Hematology and Oncology for chemotherapy. He received four cycles
      of combined chemotherapy including cyclophosphamide, doxorubicin, vincristine and
      prednisone plus rituximab, and three cycles of intrathecal chemoprophylaxis
      including methotorexate, cytosine arbinoside and prednisone. The patient is alive
      with no evidence of the disease for 7 mo after operation and will receive
      additional courses of chemotherapy.

PMID- 18609699
TI  - Multidisciplinary management of gastric and gastroesophageal cancers.
AB  - Carcinomas of the stomach and gastroesophageal junction are among the five top
      leading cancer types worldwide. In spite of radical surgical R0 resections being
      the basis of cure of gastric cancer, surgery alone provides long-term survival in
      only 30% of patients with advanced International Union Against Cancer (UICC)
      stages in Western countries because of the high risk of recurrence and
      metachronous metastases. However, recent large phase-III studies improved the
      diagnostic and therapeutic options in gastric cancers, indicating a more
      multidisciplinary management of the disease. Multimodal strategies combining
      different neoadjuvant and/or adjuvant protocols have clearly improved the gastric
      cancer prognosis when combined with surgery with curative intention. In
      particular, the perioperative (neoadjuvant, adjuvant) chemotherapy is now a well
      established new standard of care for advanced tumors. Adjuvant therapy alone
      should be carefully discussed after surgical resection, mainly in individual
      patients with large lymph node positive tumors when neoadjuvant therapy could not
      be done. The palliative treatment options have also been remarkably improved with
      new chemotherapeutic agents and will further be enhanced with targeted therapies
      such as different monoclonal antibodies. This article reviews the most relevant
      literature on the multidisciplinary management of gastric and gastroesophageal
      cancer, and discusses future strategies to improve locoregional failures.

PMID- 18609701
TI  - Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal
      tract.
AB  - Epithelial-mesenchymal transition (EMT) is a highly conserved process that has
      been well characterised in embryogenesis. Studies have shown that the aberrant
      activation of EMT in adult epithelia can promote tumour metastasis by repressing
      cell adhesion molecules, including epithelial (E)-cadherin. Reduced intracellular
      adhesion may allow tumour cells to disseminate and spread throughout the body. A
      number of transcription proteins of the Snail superfamily have been implicated in
      EMT. These proteins have been shown to be over-expressed in advanced
      gastrointestinal (GI) tumours including oesophageal adenocarcinomas, colorectal
      carcinomas, gastric and pancreatic cancers, with a concomitant reduction in the
      expression of E-cadherin. Regulators of EMT may provide novel clinical targets to
      detect GI cancers early, so that cancers previously associated with a poor
      prognosis such as pancreatic cancer can be diagnosed before they become
      inoperable. Furthermore, pharmacological therapies designed to inhibit these
      proteins will aim to prevent local and distant tumour invasion.

PMID- 18609702
TI  - Endoscopic stenting: where are we now and where can we go?
AB  - Self expanding metal stents (SEMS) play an important role in the management of
      malignant obstructing lesions in the gastrointestinal tract. Traditionally, they
      have been used for palliation in malignant gastric outlet and colonic obstruction
      and esophageal malignancy. The development of the polyflex stent, which is a
      removable self expanding plastic stent, allows temporary stent insertion for
      benign esophageal disease and possibly for patients undergoing neoadjuvant
      chemotherapy prior to esophagectomy. Potential complications of SEMS insertion
      include perforation, tumour overgrowth or ingrowth, and stent migration. Newer
      stents are being developed with the aim of increasing technical and clinical
      success rates, while reducing complication rates. Other areas of development
      include biodegradable stents for benign disease and radioactive or drug-eluting
      stents for malignant disease. It is hoped that, in the future, newer stents will
      improve our management of these difficult conditions and, possibly, provide
      prognostic as well as symptomatic benefit in the setting of malignant
      obstruction.

PMID- 18609700
TI  - Autoantibodies in primary sclerosing cholangitis.
AB  - The aetiology of primary sclerosing cholangitis (PSC) is not known and
      controversy exists as to whether PSC should be denominated an autoimmune disease.
      A large number of autoantibodies have been detected in PSC patients, but the
      specificity of these antibodies is generally low, and the frequencies vary
      largely between different studies. The presence of autoantibodies in PSC may be
      the result of a nonspecific dysregulation of the immune system, but the
      literature in PSC points to the possible presence of specific antibody targets in
      the biliary epithelium and in neutrophil granulocytes. The present review aims to
      give an overview of the studies of autoantibodies in PSC, with a particular
      emphasis on the prevalence, clinical relevance and possible pathogenetic
      importance of each individual marker.

PMID- 18609703
TI  - PCR-SSCP-DNA sequencing method in detecting PTEN gene mutation and its
      significance in human gastric cancer.
AB  - AIM: To discuss the possible effect of PTEN gene mutations on occurrence and
      development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were
      selected to probe PTEN gene mutations in genome of gastric cancer and
      paracancerous tissues using PCR-SSCP-DNA sequencing method based on
      microdissection and to observe the protein expression by immunohistochemistry
      technique. RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation
      sites were found in 5 of 53 gastric cancer specimens. One kind of mutation was
      found in exons. AA-TCC mutation was located at 40 bp upstream of 3' lateral exon
      7 (115946 AA-TCC). Such mutations led to terminator formation in the 297th codon
      of the PTEN gene. The other 3 kinds of mutation were found in introns, including
      a G-C point mutation at 91 bp upstream of 5' lateral exon 5(90896 G-C), a T-G
      point mutation at 24 bp upstream of 5' lateral exon 5 (90963 T-G), and a single
      base A mutation at 7 bp upstream of 5' lateral exon 5 (90980 A del). The PTEN
      protein expression in gastric cancer and paracancerous tissues detected using
      immunohistochemistry technique indicated that the total positive rate of PTEN
      protein expression was 66% in gastric cancer tissue, which was significantly
      lower than that (100%) in paracancerous tissues (P < 0.005). CONCLUSION: PTEN
      gene mutation and expression may play an important role in the occurrence and
      development of gastric cancer.

PMID- 18609704
TI  - Heparanase expression, degradation of basement membrane and low degree of
      infiltration by immunocytes correlate with invasion and progression of human
      gastric cancer.
AB  - AIM: To disclose the mechanisms that accelerate or limit tumor invasion and
      metastasis in gastric cancer patients. METHODS: The heparanase expression,
      continuity of basement, degree of infiltration by dendritic cells and lymphocytes
      in gastric cancer tissues from 33 the early and late stage patients were examined
      by immunohistochemistry, in situ hybridization and transmission electron
      microscopy. RESULTS: Heparanase mRNA expression in the late stage patients with
      gastric cancer was stronger than that in the early stage gastric cancer patients.
      In the early stage gastric cancer tissues, basement membrane (BM) appeared
      intact, whereas in the late stage, discontinuous BM was often present. The
      density of S100 protein positive tumor infiltrating dendritic cells (TIDC) in the
      early stage gastric cancer tissues was higher than that in the late stage. The
      infiltrating degree of tumor infiltrating lymphocytes (TIL) in the early stage
      patients whose tumor tissues contained a high density of TIDC was significantly
      higher than that in the late stage gastric cancer tissues patients with a low
      density of TIDC. There were few cancer cells penetrated through the continuous BM
      of cancer nests in the early stage gastric cancers, but many cancer cells were
      found outside of the defective BM of cancer nests in the late stage. CONCLUSION:
      Our results suggest that strong heparanase expression is related with the
      degradation of BM which allows or accelerates tumor invasion and metastasis.
      However, high density of TIDC and degree of infiltration by TIL are associated
      with tumor progression in human gastric cancers.

PMID- 18609705
TI  - Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics
      requires promyelocytic leukemia protein.
AB  - AIM: To evaluate the synergistic targeting and killing of human hepatocellular
      carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1
      and chemotherapeutic agents and its dependence on functional promyelocytic
      leukemia protein (PML). METHODS: The role of p53 and PML in regulating
      cytotoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in
      two pairs of isogenic human hepatoma cell lines with different p53 status.
      Furthermore, H-1 PV infection was combined with cytostatic drug treatment.
      RESULTS: While the HCC cells with different p53 status studied were all
      susceptible to H-1 PV-induced apoptosis, the cytotoxicity of H-1 PV was more
      pronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53
      negative cell lines treated by genotoxic drugs were further enhanced by a
      treatment with H-1 PV. In flow cytometric analyses, H-1 PV infection resulted in
      a reduction of the mitochondrial transmembrane potential. In addition, H-1 PV
      cells showed a significant increase in PML expression. Knocking down PML
      expression resulted in a striking reduction of the level of H-1 PV infected tumor
      cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance
      of p53-negative HCC cells to genotoxic agents, and it enhances the apoptotic
      process which is dependent on functional PML. Thus, H-1 PV and its oncolytic
      vector derivatives may be considered as therapeutic options for HCC, particularly
      for p53-negative tumors.

PMID- 18609707
TI  - Staging of portal hypertension and portosystemic shunts using dynamic nuclear
      medicine investigations.
AB  - AIM: To explore portal hypertension and portosystemic shunts and to stage chronic
      liver disease (CLD) based on the pathophysiology of portal hemodynamics. METHODS:
      Per-rectal portal scintigraphy (PRPS) was performed on 312 patients with CLD and
      liver angioscintigraphy (LAS) on 231 of them. The control group included 25
      healthy subjects. We developed a new model of PRPS interpretation by introducing
      two new parameters, the liver transit time (LTT) and the circulation time between
      right heart and liver (RHLT). LTT for each lobe was used to evaluate the early
      portal hypertension. RHLT is useful in cirrhosis to detect liver areas missing
      portal inflow. We calculated the classical per-rectal portal shunt index (PRSI)
      at PRPS and the hepatic perfusion index (HPI) at LAS. RESULTS: The normal LTT
      value was 24 +/- 1 s. Abnormal LTT had PPV = 100% for CLD. 27 non-cirrhotic
      patients had LTT increased up to 35 s (median 27 s). RHLT (42 +/- 1 s) was not
      related to liver disease. Cirrhosis could be excluded in all patients with PRSI <
      5% (P < 0.01). PRSI > 30% had PPV = 100% for cirrhosis. Based on PRPS and LAS we
      propose the classification of CLD in 5 hemodynamic stages. Stage 0 is normal (LTT
      = 24 s, PRSI < 5%). In stage 1, LTT is increased, while PRSI remains normal. In
      stage 2, LTT is decreased between 16 s and 23 s, whereas PRSI is increased
      between 5% and 10%. In stage 3, PRSI is increased to 10%-30%, and LTT becomes
      undetectable by PRPS due to the portosystemic shunts. Stage 4 includes the
      patients with PRSI > 30%. RHLT and HPI were used to subtype stage 4. In our study
      stage 0 had NPV = 100% for CLD, stage 1 had PPV = 100% for non-cirrhotic CLD,
      stages 2 and 3 represented the transition from chronic hepatitis to cirrhosis,
      stage 4 had PPV = 100% for cirrhosis. CONCLUSION: LTT allows the detection of
      early portal hypertension and of opening of transhepatic shunts. PRSI is useful
      in CLD with extrahepatic portosystemic shunts. Our hemodynamic model stages the
      evolution of portal hypertension and portosystemic shunts. It may be of use in
      the selection of patients for interferon therapy.

PMID- 18609706
TI  - Bcl-x(L) and Myeloid cell leukaemia-1 contribute to apoptosis resistance of
      colorectal cancer cells.
AB  - AIM: To explore the role of Bcl-x(L) and Myeloid cell leukaemia (Mcl)-1 for the
      apoptosis resistance of colorectal carcinoma (CRC) cells towards current
      treatment modalities. METHODS: Bcl-x(L) and Mcl-1 mRNA and protein expression
      were analyzed in CRC cell lines as well as human CRC tissue by Western blot,
      quantitative PCR and immunohistochemistry. Bcl-x(L) and Mcl-1 protein expression
      was knocked down or increased in CRC cell lines by applying specific siRNAs or
      expression plasmids, respectively. After modulation of protein expression, CRC
      cells were treated with chemotherapeutic agents, an antagonistic epidermal growth
      factor receptor (EGFR1) antibody, an EGFR1 tyrosine kinase inhibitor, or with the
      death receptor ligand TRAIL. Apoptosis induction and cell viability were
      analyzed. RESULTS: Here we show that in human CRC tissue and various CRC cell
      lines both Bcl-x(L) and Mcl-1 are expressed. Bcl-x(L) expression was higher in
      CRC tissue than in surrounding non-malignant tissue, both on protein and mRNA
      level. Mcl-1 mRNA expression was significantly lower in malignant tissues.
      However, protein expression was slightly higher. Viability rates of CRC cells
      were significantly decreased after knock down of Bcl-x(L) expression, and, to a
      lower extent, after knock down of Mcl-1 expression. Furthermore, cells with
      reduced Bcl-x(L) or Mcl-1 expression was more sensitive towards oxaliplatin- and
      irinotecan-induced apoptosis, and in the case of Bcl-x(L) also towards 5-FU
      induced apoptosis. On the other hand, upregulation of Bcl-x(L) by transfection of
      an expression plasmid decreased chemotherapeutic drug-induced apoptosis. EGF
      treatment clearly induced Bcl-x(L) and Mcl-1 expression in CRC cells. Apoptosis
      induction upon EGFR1 blockage by cetuximab or PD168393 was increased by
      inhibiting Mcl-1 and Bcl-x(L) expression. More strikingly, CD95- and TRAIL
      induced apoptosis was increased by Bcl-x(L) knock down. CONCLUSION: Our data
      suggest that Bcl-x(L) and, to a lower extent, Mcl-1, are important anti-apoptotic
      factors in CRC. Specific downregulation of Bcl-x(L) is a promising approach to
      sensitize CRC cells towards chemotherapy and targeted therapy.

PMID- 18609708
TI  - Combination of small interfering RNAs mediates greater suppression on hepatitis B
      virus cccDNA in HepG2.2.15 cells.
AB  - AIM: To observe the inhibition of hepatitis B virus (HBV) replication and
      expression in HepG2.2.15 cells by combination of small interfering RNAs (siRNAs).
      METHODS: Recombinant plasmid psil-HBV was constructed and transfected into
      HepG2.2.15 cells. At 48 h, 72 h and 96 h after transfection, culture media were
      collected and cells were harvested for HBV replication assay. HBsAg and HBeAg in
      the cell culture medium were detected by enzyme-linked immunoadsorbent assay
      (ELISA). Intracellular viral DNA and covalently closed circular DNA (cccDNA) were
      quantified by real-time polymerase chain reaction (PCR). HBV viral mRNA was
      reverse transcribed and quantified by reverse-transcript PCR (RT-PCR). RESULTS:
      siRNAs showed marked anti-HBV effects. siRNAs could specifically inhibit the
      expression of HBsAg and the replication of HBV DNA in a dose-dependent manner.
      Furthermore, combination of siRNAs, compared with individual use of each siRNA,
      exerted a stronger inhibition on antigen expression and viral replication. More
      importantly, combination of siRNAs significantly suppressed HBV cccDNA
      amplification. CONCLUSION: Combination of siRNAs mediates a stronger inhibition
      on viral replication and antigen expression in HepG2.2.15 cells, especially on
      cccDNA amplification.

PMID- 18609709
TI  - Treatment of Helicobacter pylori in surgical practice: a randomised trial of
      triple versus quadruple therapy in a rural district general hospital.
AB  - AIM: To compare a lansoprazole-based triple versus quadruple therapy for
      Helicobacter pylori (H pylori) eradication with emphasis on side effect profile,
      patient compliance and eradication rate at a rural district general hospital in
      Wales, United Kingdom. METHODS: One hundred one patients with H pylori infection
      were included in the study. Patients were randomised to receive triple therapy
      comprising of lansoprazole 30 mg, amoxycillin 1 g, clarithromycin 500 mg, all
      b.d. (LAC), or quadruple therapy comprising of lansoprazole 30 mg b.d.,
      metronidazole 500 mg t.d.s., bismuth subcitrate 240 mg b.d., and tetracycline
      chloride 500 mg q.d.s. (LMBT). Cure was defined as a negative (13)C urea breath
      test 2 mo after treatment. RESULTS: Seven patients were withdrawn after
      randomisation. Fifty patients were assigned to LAC group and 44 to LMBT group.
      The intention-to-treat cure rates were 92% and 91%, whereas the per-protocol cure
      rates were 92% and 97%, respectively. Side effects were common, with 56%
      experiencing moderate to severe symptoms in the LAC group and 59% in the LMBT
      group. Symptoms of vomiting, diarrhoea and black stools were significantly more
      common in the LMBT group. Patient compliance was 100% for triple therapy and 86%
      for quadruple therapy (P < 0.01). One-third of patients in both groups were still
      taking acid-reducing medications at six-month follow-up. CONCLUSION: One-week
      triple and quadruple therapies have similar intention-to-treat eradication rates.
      Certain side effects are more common with quadruple therapy, which can compromise
      patient compliance. Patient education or modifications to the regimen are
      alternative options to improve compliance of the quadruple regimen.

PMID- 18609710
TI  - Pathological evolution of hepatitis C virus-"Healthy carriers".
AB  - AIM: To determine factors associated with fibrosis progression in hepatitis C
      virus (HCV)-infected patients without significant initial pathological lesions.
      METHODS: Seventy six untreated HCV-infected patients with initially normal liver
      as defined by a Knodell score < or = 3, with 2 liver biopsies and detectable HCV
      RNA were included. Markers of fibrosis progression were assessed. RESULTS: Median
      duration of infection and time between paired biopsies was 13 (95% CI: 1-28) and
      4 (95% CI: 2-16) years respectively. Alanine-transaminase (ALT) activity was
      normal in 43.4% of cases. 50% demonstrated progression of the necro-inflammation
      and 34% of fibrosis after a median time evolution of 4 years (95% CI: 2-16). The
      median difference in the necro-inflammation and fibrosis score between biopsies
      was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no
      difference between fibrosis activity or evolution according to genotype or viral
      load. A higher fibrosis progression (P = 0.03) was observed in patients with body
      mass index (BMI) > 25. Fibrosis progression correlated with the time interval
      between biopsies (P = 0.01). A significant progression of activity (1.7 vs 0.4, P
      < 0.05) or fibrosis (0.9 vs 0.0, P < 0.01) was observed in patients with elevated
      ALT. There was a significant correlation between activity progression and
      fibrosis progression (P = 0.003). Multivariate analysis demonstrated that
      fibrosis progression was associated with elevated ALT, BMI > 25 and the time
      interval between 2 biopsies. CONCLUSION: There is no fibrosis progression in 66%
      of patients without significant initial histopathological lesion. Fibrosis
      progression is associated with elevated ALT and BMI > 25.

PMID- 18609711
TI  - Nuclear beta-catenin expression as a prognostic factor in advanced colorectal
      carcinoma.
AB  - AIM: To investigate the changing pattern of beta-catenin expression and its
      prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor
      samples were analyzed for beta-catenin using immunohistochemistry (IHC) in 95
      patients with advanced CRC. RESULTS: Membranous beta-catenin expression was found
      in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous
      and cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In
      univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a
      significant predictor of disease free survival (DFS) (P = 0.023; n = 35), with a
      NI above the median associated with longer DFS (34.2 mo) than those with a NI
      below the median (15.5 mo) (P = 0.045, ANOVA). The other indices were not
      significant predictors of DFS, and none of the three tested indices (for
      membranous, cytoplasmic, or nuclear expression) predicted disease-specific
      survival (DSS). However, when dichotomized as positive or negative nuclear
      expression, the former was a significant predictor of more favorable DFS (P =
      0.041) and DSS (P = 0.046). CONCLUSION: Nuclear beta-catenin expression provides
      additional information in predicting patient outcome in advanced CRC.

PMID- 18609712
TI  - Intrahepatic CD8(+) lymphocyte trapping during tolerance induction using mushroom
      derived formulations: a possible role for liver in tolerance induction.
AB  - AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),
      we tested its effect on liver-mediated immune regulation in a model of immune
      mediated colitis. METHODS: Four groups of mice were studied. Colitis was induced
      by intracolonic instillation of TNBS in groups A and B. Groups A and C were
      treated daily with Shiitake extract, while groups B and D received bovine serum
      albumin. Mice were evaluated for development of macroscopic and microscopic. The
      immune effects of Shiitake were determined by FACS analysis of intra-hepatic and
      intrasplenic lymphocytes and IFN-gamma ELISPOT assay. RESULTS: Administration of
      Shiitake resulted in marked alleviation of colitis, manifested by significant
      improvement in the macroscopic and microscopic scores, and by reduction in IFN
      gamma-producing colonies in group A, compared to group B mice (1.5 pfu/mL vs 3.7
      pfu/mL, respectively). This beneficial effect was associated with a significant
      increase in the intra-hepatic CD8(+) lymphocyte trapping, demonstrated by an
      increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio. These effects were
      accompanied by a 17% increase in the number of intrahepatic natural killer T
      (NKT) cells. A similar effect was observed when Shiitake was administered to
      animals without disease induction. CONCLUSION: Shiitake extract affected liver
      mediated immune regulation by altering the NKT lymphocyte distribution and
      increasing intrahepatic CD8(+) T lymphocyte trapping, thereby leading to
      alleviation of immune-mediated colitis.

PMID- 18609713
TI  - Measurement of circulating levels of VEGF-A, -C, and -D and their receptors,
      VEGFR-1 and -2 in gastric adenocarcinoma.
AB  - AIM: To analyze the serum levels and prognostic significance of vascular
      endothelial growth factor (VEGF) -A, -C, and -D, and their receptors, VEGFR-1 and
      -2 in gastric adenocarcinomas. METHODS: The serum levels of VEGF family members
      were measured in 76 control subjects and 76 patients with gastric adenocarcinoma
      using an enzyme-linked immunosorbent assay (ELISA). These measurements were
      correlated with clinco-pathological features and survival rates. RESULTS: The
      serum levels of VEGF-A and its receptor, VEGFR-1, were significantly higher in
      patients with gastric cancer than in healthy donors (t = 2.3, P = 0.02 and t =
      4.2, P < 0.0001, respectively). In contrast, the serum levels of VEGF-D were
      significantly higher in control subjects than in patients (t = 2.9, P = 0.004).
      There was no significant difference in serum levels of VEGF-C and VEGFR-2 between
      patients and controls. VEGF-C was associated with advanced tumor stage and
      presence of metastasis. VEGFR-1 was associated with metastasis, advanced overall
      stage, tumor differentiation and survival. VEGFR-2 levels were associated with
      poor tumor differentiation. There was no significant prognostic value for any of
      the VEGF family members or their receptors except for VEGFR-1 where high levels
      were associated with a poor overall survival. CONCLUSION: Serum VEGF levels vary
      significantly in the same cohort of patients with variable clinico-pathological
      features and prognostic values. The simultaneous measurement of VEGF receptors
      levels in sera may overcome the limitations of a single biomarker assay.

PMID- 18609714
TI  - Increased intestinal macromolecular permeability and urine nitrite excretion
      associated with liver cirrhosis with ascites.
AB  - AIM: To determine intestinal permeability, the serum tumor necrosis factor (TNF)
      alpha level and urine nitric oxide (NO) metabolites are altered in liver
      cirrhosis (LC) with or without ascites. METHODS: Fifty-three patients with LC and
      26 healthy control subjects were enrolled in the study. The intestinal
      permeability value is expressed as the percentage of polyethylene glycol (PEG)
      400 and 3350 retrieval in 8-h urine samples as determined by high performance
      liquid chromatography. Serum TNF-alpha concentrations and urine NO metabolites
      were determined using an enzyme-linked immunosorbent assay (ELISA) and Greiss
      reaction method, respectively. RESULTS: The intestinal permeability index was
      significantly higher in patients with LC with ascites than in healthy control
      subjects or patients with LC without ascites (0.88 +/- 0.12 vs 0.52 +/- 0.05 or
      0.53 +/- 0.03, P < 0.05) and correlated with urine nitrite excretion (r = 0.98).
      Interestingly, the serum TNF-alpha concentration was significantly higher in LC
      without ascites than in control subjects or in LC with ascites (198.9 +/- 55.8
      pg/mL vs 40.9 +/- 12.3 pg/mL or 32.1 +/- 13.3 pg/mL, P < 0.05). Urine nitrite
      excretion was significantly higher in LC with ascites than in the control
      subjects or in LC without ascites (1170.9 +/- 28.7 micromol/L vs 903.1 +/- 55.1
      micromol/L or 956.7 +/- 47.7 micromol/L, P < 0.05). CONCLUSION: Increased
      intestinal macromolecular permeability and NO is probably of importance in the
      pathophysiology and progression of LC with ascites, but the serum TNF-alpha
      concentration was not related to LC with ascites.

PMID- 18609715
TI  - Change of choline compounds in sodium selenite-induced apoptosis of rats used as
      quantitative analysis by in vitro 9.4T MR spectroscopy.
AB  - AIM: To study liver cell apoptosis caused by the toxicity of selenium and observe
      the alteration of choline compounds using in vitro 9.4T high resolution magnetic
      resonance spectroscopy. METHODS: Twenty male Wistar rats were randomly divided
      into two groups. The rats in the treatment group were intraperitoneally injected
      with sodium selenite and the control group with distilled water. All rats were
      sacrificed and the livers were dissected. (1)H-MRS data were collected using in
      vitro 9.4T high resolution magnetic resonance spectrometer. Spectra were
      processed using XWINNMR and MestRe-c 4.3. HE and TUNEL staining was employed to
      detect and confirm the change of liver cells. RESULTS: Good (1)H-MR spectra of
      perchloric acid extract from liver tissue of rats were obtained. The conventional
      metabolites were detected and assigned. Concentrations of different ingredient
      choline compounds in treatment group vs control group were as follows: total
      choline compounds, 5.08 +/- 0.97 mmol/L vs 3.81 +/- 1.16 mmol/L (P = 0.05); and
      free choline, 1.07 +/- 0.23 mmol/L vs 0.65 +/- 0.20 mmol/L (P = 0.00). However,
      there was no statistical significance between the two groups. The hepatic sinus
      and cellular structure of hepatic cells in treatment group were abnormal.
      Apoptosis of hepatic cells was confirmed by TUNEL assay. CONCLUSION: High dose
      selenium compounds can cause the rat liver lesion and induce cell apoptosis in
      vivo. High resolution (1)H-MRS in vitro can detect diversified metabolism. The
      changing trend for different ingredient of choline compounds is not completely
      the same at early period of apoptosis.

PMID- 18609716
TI  - 1,25-dihydroxyvitamin D(3) regulates LPS-induced cytokine production and reduces
      mortality in rats.
AB  - AIM: To study the immunoregulatory effect of 1,25-dihydroxyvitamin-D(3) Von
      dominant Th1 response in rats. METHODS: Sixty adult Lewis rats were randomized
      into three groups. Rats in group 1 (n=25) were treated with 1,25-(OH)(2)D(3)
      first and then challenged with LPS, rats in group 2 (n=25) were treated with
      vehicle first and then challenged with LPS. Ten animals in groups 1 and 2 were
      preserved for mortality observation. The remaining animals were injected (i.p)
      with endotoxin, 24 h after the last administration of 1,25-(OH)(2)D(3) and
      vehicle. Rats in group 3 (n=10) were treated with 1,25-(OH)(2)D(3) only. Serum IL
      12, IFN-gamma, IL-2 and IL-4 levels were measured and target gene of 1,25
      (OH)(2)D(3) on Th cells was studied after 6 h. Gene abundance was verified by
      real-time quantitative PCR. RESULTS: No death occurred in rats pretreated with
      1,25-(OH)(2)D(3) after LPS injection. Death occurred 9 h after LPS injection in
      rats pretreated with the vehicle, and the number of deaths was 5 within 24 h,
      with a mortality rate of 50%. There was no change in the number of deaths within
      96 h. Six hours after endotoxin stimulation, serum IL-12 and IFN-gamma levels
      decreased significantly in rats pretreated with 1,25-(OH)(2)D(3) as compared with
      those in rats pretreated with the vehicle. The serum content of these two
      cytokines was very low in rats not challenged by endotoxin, and there was a
      significant difference as compared with the previous two groups. CONCLUSION: 1,25
      (OH)(2)D(3) attenuates injury induced by the lethal dose of LPS, regulates Th1
      and Th2 cells at the transcription level, and dominantly responds to cytokine
      production in rats.

PMID- 18609717
TI  - Isolation and biological analysis of tumor stem cells from pancreatic
      adenocarcinoma.
AB  - AIM: To explore the method of isolation and biological analysis of tumor stem
      cells from pancreatic adenocarcinoma cell line PANC-1. METHODS: The PANC-1 cells
      were cultured in Dulbecco modified eagle medium F12 (1:1 volume) (DMEM-F12)
      supplemented with 20% fetal bovine serum (FBS). Subpopulation cells with
      properties of tumor stem cells were isolated from pancreatic adenocarcinoma cell
      line PANC-1 according to the cell surface markers CD44 and CD24 by flow
      cytometry. The proliferative capability of these cells in vitro were estimated by
      3-[4,5-dimehyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method.
      And the tumor growth of different subpopulation cells which were injected into
      the hypodermisof right and left armpit of nude mice was studied, and expression
      of CD44 and CD24 of the CD44(+)CD24(+) cell-formed nodules and PANC-1 cells were
      detected by avidin-biotin-peroxidase complex (ABC) immunohistochemical staining.
      RESULTS: The 5.1%-17.5% of sorted PANC-1 cells expressed the cell surface marker
      CD44, 57.8% -70.1% expressed CD24, only 2.1%-3.5% of cells were CD44(+) CD24(+).
      Compared with CD44(-)CD24(-) cells, CD44(+)CD24(+) cells had a lower growth rate
      in vitro. Implantation of 10(4) CD44(-)CD24(-) cells in nude mice showed no
      evident tumor growth at wk 12. In contrast, large tumors were found in nude mice
      implanted with 10(3) CD44(+)CD24(+) cells at wk 4 (2/8), a 20-fold increase in
      tumorigenic potential (P < 0.05 or P < 0.01). There was no obvious histological
      difference between the cells of the CD44(+)CD24(+) cell-formed nodules and PANC-1
      cells. CONCLUSION: CD44 and CD24 may be used as the cell surface markers for
      isolation of pancreatic cancer stem cells from pancreatic adenocarcinoma cell
      line PANC-1. Subpopulation cells CD44(+)CD24(+) have properties of tumor stem
      cells. Because cancer stem cells are thought to be responsible for tumor
      initiation and its recurrence after an initial response to chemotherapy, it may
      be a very promising target for new drug development.

PMID- 18609718
TI  - Assessment of hepatic VX(2) tumors with combined percutaneous transhepatic
      lymphosonography and contrast-enhanced ultrasonographic imaging.
AB  - AIM: To evaluate the feasibility and efficacy of percutaneous transhepatic
      lymphosonography (PTL) as a novel method for the detection of tumor
      lymphangiogenesis in hepatic VX(2) of rabbits and to evaluate combined PTL and
      routine contrast-enhanced ultrasonographic imaging for the diagnosis of liver
      cancer. METHODS: Ten rabbits with VX(2) tumor were included in this study.
      SonoVue (0.1 mL/kg) was injected into each rabbit via an ear vein for contrast
      enhanced ultrasonographic imaging, and 0.5 mL SonoVue was injected into the
      normal liver parenchyma near the VX(2) tumor for PTL. Images and/or movie clips
      were stored for further analysis. RESULTS: Ultrasonographic imaging showed VX(2)
      tumors ranging 5-19 mm in the liver of rabbits. The VX(2) tumor was hyperechoic
      and hypoechoic to liver parenchyma at the early and later phase, respectively.
      The hepatic lymph vessels were visualized immediately after injection of contrast
      medium and continuously visualized with SonoVue during PTL. The boundaries of
      VX(2) tumors were hyperechoic to liver parenchyma and the tumors. There was a
      significant difference in the values for the boundaries of VX(2) tumors after
      injection compared with the liver normal parenchyma and the tumor parenchyma
      during PTL. CONCLUSION: PTL is a novel method for the detection of tumor
      lymphangiogenesis in hepatic VX(2) of rabbits. Combined PTL and contrast-enhanced
      ultrasonographic imaging can improve the diagnosis of liver cancer.

PMID- 18609719
TI  - Tuberculosis versus non-Hodgkin's lymphomas involving small bowel mesentery:
      evaluation with contrast-enhanced computed tomography.
AB  - AIM: To evaluate the specific computed tomography (CT) imaging criteria for
      differentiating tuberculosis involving the small bowel mesenteric lymph nodes
      from lymphomas. METHODS: We retrospectively reviewed the anatomic distribution,
      CT enhancement patterns of lymphoma in 18 patients with mesenteric tuberculosis
      and 22 with untreated non-Hodgkin's lymphomas (NHL) involving small bowel
      mesentery (SBM). Of the 18 patients with tuberculosis, 9 had purely mesenteric
      tuberculous lymphadenopathy (TL), and 9 had mesenteric TL accompanied with
      tuberculous mesenteritis (TLM). RESULTS: CT showed that tuberculosis and NHL
      mainly affected lymph nodes in the body and root of SBM. Homogeneously enhanced
      lymph nodes in the body and root of SBM were found more often in the NHL (P <
      0.05). Homogeneously mixed peripheral enhanced lymph nodes in the body of SBM
      were found more often in mesenteric TL and TLM (P < 0.05). Peripheral enhanced
      lymph nodes in the root of SBM were found more often in mesenteric TL and TLM (P
      < 0.01). "Sandwich sign" in the root of SBM was observed more often in NHL (P <
      0.05). CONCLUSION: Anatomic lymph node distribution, sandwich sign and specific
      enhancement patterns of lymphadenopathy in SBM on CT images can be used in
      differentiating between tuberculosis and untreated NHL involving SBM.

PMID- 18609720
TI  - A new approach to endoscopic treatment of tumors of the esophagogastric junction
      with individually designed self-expanding metal stents.
AB  - The incidence of adenocarcinoma of the esophago-gastric junction is constantly
      increasing. Curative treatment is no longer possible at the time of diagnosis in
      more than 50% of patients with esophageal carcinoma, and palliative treatment
      focusing on eliminating dysphagia is required. Endoscopic therapy with stent
      implantation is an established method of achieving this. It can be carried out
      quickly, with a low rate of early complications, and leads to fast symptomatic
      improvement, assessed using the dysphagia score. The relatively high rate of late
      complications such as stent migration, hemorrhage, and gastroesophageal mucosal
      prolapse has led to recent debate on the role of metal stents in palliative
      therapy. We present here a new type of stent design for transcardial application,
      which is intended to prevent bleeding due to mechanical mucosal lesions caused by
      the distal end of the stent extending into the stomach. The further intention of
      this case report is to force the discussion on individually designed nitinol
      stents in special anatomic conditions.

PMID- 18609721
TI  - Subcutaneous cervical emphysema and pneumomediastinum due to a lower
      gastrointestinal tract perforation.
AB  - This case report describes a 69-year-old man presenting with an extensive
      subcutaneous emphysema in his neck and generalized peritonitis caused by a lower
      gastrointestinal tract perforation. This case emphasizes that subcutaneous
      emphysema patients with negative thoracic findings should be scrutinized for
      signs of retroperitoneal hollow viscus perforation.

PMID- 18609722
TI  - Duplication cyst of the small intestine found by double-balloon endoscopy: a case
      report.
AB  - A 35-year-old man was admitted due to bloody stool and anemia. The bleeding
      source could not be detected by esophagogastroduodenoscopy or colonoscopy. Double
      balloon endoscopy (DBE) revealed a diverticulum-like hole in which coagula stuck
      in the ileum at 1 meter on the oral side from the ileocecal valve. The adjacent
      mucosa just to the oral side of the hole was elevated like a submucosal tumor.
      The lesion was considered the source of bleeding and removed surgically. It was
      determined to be a cyst with an ileal structure on the mesenteric aspect
      accompanying gastric mucosa. The diagnosis was a duplication cyst of the ileum,
      which is a rare entity that can cause gastrointestinal bleeding. In the present
      case, DBE was used to find the hemorrhagic duplication cyst in the ileum.

PMID- 18609723
TI  - Intraperitoneal metastasis of hepatocellular carcinoma after spontaneous rupture:
      a case report.
AB  - Rupture of hepatocellular carcinoma (HCC) is a life-threatening complication.
      Peritoneal metastasis of HCC after spontaneous rupture was seldom noted. We
      report a case of intraperitoneal metastasis of HCC after spontaneous rupture. A
      previously asymptomatic 72-year-old man was admitted due to dull abdominal pain
      with abdominal fullness. He had a history of HCC rupture 10 mo ago and
      transarterial embolization was performed at that time. Abdominal computer
      tomography (CT) scan showed a huge peritoneal mass over the right upper quadrant
      area. Surgical resection was arranged and subsequent microscopic examination
      confirmed a diagnosis of moderately-differentiated HCC.

PMID- 18609724
TI  - Early spondyloarthritis in an HLA-B27-positive monozygotic twin pair: A highly
      concordant onset, sites of involvement, and disease course.

PMID- 18609725
TI  - Usefulness of enzyme-linked immunosorbent assay (Elispot) compared to tuberculin
      skin testing for latent tuberculosis screening in rheumatic patients scheduled
      for anti-tumor necrosis factor treatment. Addendum.

PMID- 18609726
TI  - Clinical hand osteoarthritis in Tehran: prevalence, signs, symptoms, and pattern 
      COPCORD stage I, Iran study.

PMID- 18609727
TI  - Demyelinating disease associated with use of etanercept in patients with
      seronegative spondyloarthropathies.

PMID- 18609728
TI  - Recovery from multiple cranial nerve palsy of Wegener's granulomatosis with
      infliximab.

PMID- 18609729
TI  - Improving access to rheumatology care: a continuing challenge.

PMID- 18609730
TI  - Quantitative clinical assessment in busy rheumatology settings: the value of
      short patient questionnaires.

PMID- 18609731
TI  - Pregnant adolescents and youth with systemic lupus erythematosus: can new data
      inform our approach to young women with SLE?

PMID- 18609732
TI  - Central nervous system abnormalities in fibromyalgia: assessment using proton
      magnetic resonance spectroscopy.

PMID- 18609733
TI  - B cell-targeted therapy in autoimmune disease: rationale, mechanisms, and
      clinical application.
AB  - B cells play a critical role in the pathogenesis of rheumatoid arthritis (RA) and
      other autoimmune diseases. Recently, a number of biologic agents that target B
      cells have been tested as therapies for these conditions. These agents either
      deplete B cells, by targeting cell-surface antigens such as CD20, or block B cell
      function, for example by inhibiting the activity of B cell survival factors such
      as BLyS. Of this group of agents, the first in clinical use has been rituximab, a
      chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell
      surface antigen. Initially introduced as a treatment for non-Hodgkin's lymphoma,
      rituximab is now approved for the treatment of RA. In this review we explore the
      rationale behind B cell-targeted therapy, highlight the results of clinical
      trials with rituximab in RA and other autoimmune diseases, and describe other
      emerging therapies directed at B cells.

PMID- 18609734
TI  - No improvement in survival of patients with amyloidosis associated with
      inflammatory rheumatic diseases -- data from the Finnish national registry for
      kidney diseases.
AB  - OBJECTIVE: To assess the incidence and outcome of renal replacement therapy (RRT)
      among patients with amyloidosis associated with inflammatory rheumatic diseases.
      METHODS: Patients with amyloidosis entering RRT from 1987 to 2002 were identified
      from the Finnish Registry for Kidney Diseases. Five hundred two patients were
      identified, 80% of whom had amyloidosis associated with an underlying rheumatic
      disease. They were followed from the time of entering RRT until death or until
      the end of 2003 using the Finnish national mortality files. RESULTS: During the
      study period, there was no decline in the number of patients with amyloidosis
      entering RRT. Mean age of patients with rheumatoid arthritis (RA) and juvenile
      idiopathic arthritis (JIA) increased significantly from 1987 to 2002 (p < 0.001).
      Male sex and a diagnosis of JIA indicated an increased risk of mortality. The
      median survival time after entering RRT was 2.11 years for RA (95% CI 1.93 to
      2.69), 2.37 years for ankylosing spondylitis (95% CI 1.11 to 4.31), and 3.05
      years for JIA (95% CI 2.19 to 4.23). The 5-year survival rates among patients
      with the corresponding diagnoses were 18% (95% CI 14% to 23%), 30% (95% CI 14% to
      48%), and 27% (95% CI 14% to 41%), respectively. CONCLUSION: No decline was seen
      in the number of patients with amyloidosis associated with inflammatory rheumatic
      diseases accepted for RRT, but over the years, the age of patients with RA or JIA
      entering RRT was seen to increase. The outcome of patients with amyloidosis and
      endstage renal disease associated with rheumatic diseases remains poor.

PMID- 18609735
TI  - Mimicry of a rheumatoid nodule by tophaceous pseudogout at the elbow.

PMID- 18609736
TI  - GRAPPA 2007: Group for Research and Assessment of Psoriasis and Psoriatic
      Arthritis.

PMID- 18609737
TI  - Psoriatic arthritis screening tools.
AB  - Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis,
      with an indolent and progressive course. A delay in diagnosis and treatment may
      lead to an erosive arthropathy, leading further to physical disability and
      deformity. To help clinicians screen for PsA, the Group for Research and
      Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has led an effort to
      develop and validate 3 PsA screening tools. Administration of a well designed
      screening tool can increase detection of PsA, help determine the prevalence of
      PsA in a given population, record clinical data for genotype-phenotype studies,
      and track response to therapy. The development and validation of these screening
      tools was a major focus at the GRAPPA annual meeting at Boston in September 2007;
      we summarize that portion of the meeting.

PMID- 18609738
TI  - Assessment tools in psoriatic arthritis.
AB  - A key objective of the assessment working group of the Group for Research and
      Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was to identify,
      develop, evaluate, and validate outcome measures for use in clinical trials of
      psoriatic arthritis (PsA) and in clinical practice. In plenary and breakout
      sessions at the GRAPPA annual meeting (Boston, September 2007), the current
      status of measures used in clinical trials was reviewed, and development of
      simplified measures for use in various types of clinical practice (rheumatology,
      dermatology, and general practice) was discussed. We present a review of those
      discussions.

PMID- 18609739
TI  - Initiative for quality in psoriasis and psoriatic arthritis.
AB  - Psoriasis is a common and severe skin disease. Up to 30% of psoriasis patients
      develop psoriatic arthritis (PsA), another severe disease that contributes
      significantly to the burden of psoriatic disease in patients. The treatment of
      patients with both psoriasis and PsA is particularly challenging, because
      different strategies are often followed, and considerable resources are needed
      for these chronic inflammatory diseases. Of note, psoriasis patients tend to be
      undertreated. Efforts to improve the management of psoriasis and PsA are urgently
      needed, to incorporate improvement of patient outcomes by promotion of best
      practice from both the medical and the pharmacoeconomic perspective. These are
      the goals of the Quality Movement in the USA and of quality management in
      general. The need for evidence-based guidance on safety, efficacy, overall
      outcome, and cost-effectiveness is being addressed by numerous initiatives
      striving to generate practice guidelines, control costs, and optimize cost
      effectiveness of treatments. The 2007 Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis's (GRAPPA) Initiative for Quality aims to
      secure and improve management of psoriasis and PsA, elaborating on these evidence
      based guidelines by defining major domains of quality and creating a checklist
      that identifies physicians who can administer state-of-the-art medical services
      to patients who need their services.

PMID- 18609740
TI  - From skin to bone: translational perspectives on psoriatic disease.
AB  - In recent years, translational research has provided fresh insights into the
      mechanisms that underlie both skin and joint inflammation in psoriatic arthritis
      (PsA). Application of immunological and molecular techniques to the study of
      involved tissues, combined with magnetic resonance imaging and relevant
      preclinical models, has unveiled pivotal inflammatory cascades and cytokine
      networks that lead to sustained inflammation and altered tissue architecture. In
      this brief overview of a presentation from the 2007 Annual Meeting of the Group
      for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) the key
      pathophysiologic events associated with inflammation in psoriatic plaques,
      synovial membranes, and soft tissues (entheses, tendons), and with abnormal bone
      remodeling are discussed.

PMID- 18609741
TI  - Clues to the pathogenesis of psoriasis and psoriatic arthritis from imaging: a
      literature review.
AB  - This article summarizes a presentation on imaging of skin and joints in patients
      with psoriasis and psoriatic arthritis (PsA) from the 2007 Annual Meeting of the
      Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
      Plain radiography provides valuable insights into the pathogenesis of PsA but is
      limited because only calcified tissue can be imaged. Newer techniques such as
      magnetic resonance imaging (MRI) and ultrasound (US) provide additional clues to
      the pathogenesis of this peripheral, axial, and dermatologic disease. MRI and to
      a lesser extent US allow visualization of articular and periarticular structures,
      showing widespread juxtaarticular inflammation in PsA. Bone edema, a surrogate
      marker of inflammation, can occur throughout the digit in psoriatic dactylitis.
      Localization of inflammatory change at the juxtaarticular entheses suggests this
      as the primary site of inflammation. Recent imaging studies provide insights into
      the relationship between nail and articular disease, demonstrating extension of
      inflammation from entheseal structures at the distal interphalangeal joint to the
      nail bed, but the temporal or anatomical progression of these changes remains
      elusive. Imaging of the skin lags behind that of the articular structures, partly
      because the skin is readily available for biopsy; however, newer techniques such
      as laser Doppler imaging provide insights into angiogenesis at the advancing edge
      of psoriatic plaques. Future work will explore the relationship between
      immunohistology and imaging of skin and joints. Improvements in imaging articular
      soft tissues with ultra-short echo time MRI and skin with multiphoton
      fluorescence microscopy promise insights into anatomical and functional changes.

PMID- 18609742
TI  - Biological biomarkers in psoriatic disease. A review.
AB  - Biomarkers are important in clinical practice because they allow quantitative
      assessment of diagnosis, disease processes, and treatment response. However,
      because development of biomarkers lags significantly behind that of drug
      development, absence of new and appropriate markers may slow the development of
      patient-tailored targeted therapies. At the 2007 Annual Meeting of the Group for
      Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members of
      the biomarker committee discussed the possible use of biomarkers in psoriasis and
      psoriatic arthritis and reviewed the results of several studies of biomarkers in
      the pathogenesis, diagnosis, and treatment of both the inflammatory and
      dermatologic aspects of psoriatic disease. We review those discussions.

PMID- 18609744
TI  - Drug use and toxicity in psoriatic disease: focus on methotrexate.
AB  - Methotrexate (MTX) toxicity in psoriatic disease was the focus of discussion at
      the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and
      Psoriatic Arthritis (GRAPPA). Plenary presentations and results of a Web-based
      opinion survey of rheumatologists and dermatologists from GRAPPA, and others from
      New Zealand, Australia, and Canada, provided topics of discussion for small-group
      breakout sessions, including hepatotoxicity, alcohol use, fertility and
      pregnancy, and combination therapy. As a framework, topics were considered under
      headings: importance, knowledge deficit, sufficient data for a recommendation,
      and research agenda. Breakout session conclusions/consensus were as follows: (1)
      Data are insufficient to recommend routine serial liver biopsy to prevent MTX
      induced liver fibrosis; further research is needed to establish whether serial
      liver chemistry tests or propeptide of type III collagen can detect
      hepatotoxicity without the need for liver biopsy. (2) Insufficient data are
      available to establish a dose-response relationship between alcohol use and MTX
      hepatotoxicity, so no safe limit of alcohol intake can be recommended. (3)
      Although cessation of MTX 3 months prior to conception is reasonable, inadequate
      data are available to specify duration or to quantify the risk of adverse fetal
      outcome; registries to track pregnancy outcome are potentially useful. (4)
      Combination therapy with anti-TNF agents or sulfasalazine is safe, but
      insufficient data are available for combinations with leflunomide or
      cyclosporine.

PMID- 18609743
TI  - Genetics of psoriasis and psoriatic arthritis: update and future direction.
AB  - Psoriasis and psoriatic arthritis (PsA) both have substantive genetic
      determinants. Numerous candidate regions and genes have now been replicated in
      disease susceptibility, and to a lesser extent in disease expression, in both
      disease entities. Intensive efforts are now under way or are being planned to
      perform genome-wide association scans (GWAS) in psoriasis and PsA. A major
      determinant of success for GWAS is likely to be accumulation of multiple large
      well-phenotyped cohorts, sophisticated data management, and verification of the
      findings. At the 2007 Annual Meeting of the Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis (GRAPPA), members of the GRAPPA genetics
      committee presented a discussion of the genetics of psoriasis and PsA, including
      future trends. This article is a summary of that presentation and a review of the
      literature.

PMID- 18609745
TI  - Clinical and genetic registries in psoriatic disease.
AB  - Clinical and genetic registries are an important tool in studying psoriasis and
      psoriatic arthritis (PsA). They assist in delineating disease features and are
      crucial in defining phenotype and identifying genetic and other markers of
      disease expression. At the 2007 Annual Meeting of the Group for Research and
      Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members of the clinical
      registries and genetics committees described several ongoing registries,
      including their construction, protocols, and some results from their analyses. In
      breakout groups, members discussed data issues, including identification of core
      datasets, ownership, and how to share data; and ethical issues and possible
      sources of funding for registries. Proceedings of these meetings are summarized.

PMID- 18609747
TI  - LIMS and the art of MS proteomics.

PMID- 18609746
TI  - A chemical killer unmasked.

PMID- 18609748
TI  - Mechanical ventilation and disuse atrophy of the diaphragm.

PMID- 18609749
TI  - Mechanical ventilation and disuse atrophy of the diaphragm.

PMID- 18609750
TI  - Mechanical ventilation and disuse atrophy of the diaphragm.

PMID- 18609751
TI  - Mechanical ventilation and disuse atrophy of the diaphragm.

PMID- 18609752
TI  - Cholesterol gene polymorphisms and cardiovascular events.

PMID- 18609753
TI  - Bibliography. Current world literature. Anaphylaxis and insect allergy.

PMID- 18609754
TI  - Imiquimod for vulvar intraepithelial neoplasia.

PMID- 18609755
TI  - Hydroxyurea for sickle cell anemia.

PMID- 18609756
TI  - Prevalence of human papillomavirus in Indonesia: a population-based study in
      three regions.
AB  - Cervical cancer is the most common cancer among women in the Indonesian
      population, yet little is known about the prevalence of human papillomavirus
      (HPV). We investigated age-specific prevalence of HPV types and possible risk
      factors of HPV positivity in a population-based sample of 2686 women, aged 15-70
      years, in Jakarta, Tasikmalaya, and Bali, Indonesia. The overall HPV prevalence
      was 11.4%, age-standardized to the world standard population 11.6%. The most
      prevalent types found were HPV 52, HPV 16, HPV 18, and HPV 39, respectively,
      23.2, 18.0, 16.1, and 11.8% of the high-risk HPV types. In 20.7% of infections,
      multiple types were involved. Different age-specific prevalence patterns were
      seen: overall high in Jakarta, and in Tasikmalaya, and declining with age in
      Bali. The number of marriages was most associated with HPV positivity (OR 1.81
      95% CI 1.31-2.51)). Remarkably, in Indonesia HPV 16 and HPV 18 are equally common
      in the general population, as they are in cervical cancer. HPV 52 was the most
      prevalent type in the general population, suggesting that this type should be
      included when prophylactic HPV vaccination is introduced in Indonesia.

PMID- 18609757
TI  - Pilot and plant scaled production of ACE inhibitory hydrolysates  from Acetes
      chinensis and its in vivo antihypertensive effect.
AB  - The angiotensin-I-converting enzyme (ACE) inhibitory oligopeptide-enriched
      hydrolysates from Acetes chinensis by treatment with the protease from Bacillus
      sp. SM98011 were produced at pilot scale (100 L) and plant scale (1000 L). The
      pilot and plant scaled hydrolysate products almost had the same properties as
      that at laboratory scale. Spray-drying had little effect on the peptide
      composition and bioactivity of the hydrolysates. The plant scaled hydrolysates
      were used to study its blood pressure-depressing effect in vivo. It caused reduce
      of 18.3-38.6 mmHg of the blood pressure of spontaneously hypertensive rats in
      dose-dependent manner in the range of 100-1,200 mg/kg/day. Histopathologic study
      showed that the pathologic changes of heart and brain in SHRs got obvious
      alleviation after treatment of the hydrolysates.

PMID- 18609758
TI  - UK ramps up embryo research debate.

PMID- 18609759
TI  - Cod spawning hot spots mapped.

PMID- 18609760
TI  - Thames delight.

PMID- 18609761
TI  - 2006 Harben Lecture. World poverty and population health: the need for
      sustainable change.
AB  - Despite important recent initiatives to improve the health of the most
      disadvantaged in the world (the Millennium Development Goals, debt cancellation
      campaigns), poverty and preventable diseases still plague many parts of the
      globe. Sub-Saharan Africa remains one of the most severely affected. It is the
      only region in the world where life expectancy has not seen much improvement.
      Some countries have employed strategies of investment in public services, such as
      education, with positive results (e.g. the 'tiger economies'). Others have tried
      to follow prescribed strategies from global institutions such as the
      International Monetary Fund and World Bank with varying degrees of success.
      Sustainable development will require continuous commitment from donors and
      recipients to long-term strategies. Oxfam believes investment in public services
      and education is key to sustainability, in combination with more effective debt
      cancellation. These concepts are explored in the 2006 Harben Lecture given by
      Barbara Stocking, Director of Oxfam.

PMID- 18609762
TI  - New wrinkle in digital microfluidics.

PMID- 18609763
TI  - Microbial forensics: DNA fingerprinting of Bacillus anthracis (anthrax).

PMID- 18609764
TI  - Surgical techniques in substitution urethroplasty using buccal mucosa for the
      treatment of anterior urethral strictures.
AB  - OBJECTIVES: Since the resurgence in the use of buccal mucosa (BM) in substitution
      urethroplasty in the late 1980s and early 1990s, there has been controversy as to
      which surgical technique is the most appropriate for its application. METHODS:
      The authors performed an updated literature review. Several centres have
      published widely on this topic, and the points considered include the use BM in
      dorsal onlay grafts, ventral onlay grafts, and tubularised grafts and the role of
      two-stage procedures. RESULTS: In experienced hands, the outcomes of both dorsal
      onlay grafts and ventral onlay grafts in bulbar urethroplasty are similar. The
      dorsal onlay technique is, however, possibly less dependent on surgical expertise
      and therefore more suitable for surgeons new to the practice of urethroplasty.
      The complications associated with ventral onlay techniques can be minimised by
      meticulous surgical technique, but in series with longer follow-up, complications
      still tend to be more prevalent. In penile urethroplasty, two-stage dorsal onlay
      of BM (after complete excision of the scarred urethra) still provides the best
      results, although in certain circumstances a one-stage dorsal onlay procedure is
      possible. In general, ventral onlay of BM and tube graft procedures in the
      management of penile strictures are associated with much higher rates of
      recurrence and should therefore be avoided. CONCLUSIONS: In experienced hands the
      results of the ventral and dorsal onlay of BM for bulbar urethroplasty are
      equivalent. Two-stage procedures are preferable in the penile urethra, except
      under certain circumstances when a one-stage dorsal onlay is feasible.

PMID- 18609765
TI  - Fertilizing value of broiler litter: effects of drying and pelletizing.
AB  - The effects of drying and pelletizing on the properties of broiler chicken
      litter, obtained from a farm in northwest Spain, were investigated. The drying
      and pelletizing process reduced among-batch variability in dry matter content,
      electrical conductivity, urea N, and K, S, Na, Fe, Cu and Cd contents, but
      increased among-batch variability in total N, ammonium N, nitrate N, total P and
      pH. N form contents in the pelletized product could be estimated with reasonable
      accuracy on the basis of dry matter content. Cr, Cu and Cd contents were all
      significantly lower in the dried pelletized product than in fresh litter, whereas
      Pb content was significantly higher. The dried pelletized product is of course
      clearly preferable to the fresh product as regards storage and handling, however,
      our results suggest a need to optimize the production process with the aim of
      reducing possible contamination during manufacture, and of minimizing variability
      in N form contents, P content and pH.

PMID- 18609766
TI  - Gamma-linolenic acid production by Cunninghamella echinulata growing on complex
      organic nitrogen sources.
AB  - Growth of two strains of Cunninghamella echinulata on various nitrogen containing
      raw materials (corn gluten, corn steep, whey concentrate,yeast extract and tomato
      waste hydrolysate) yielded important amounts of biomass containing various
      quantities of gamma-linolenic acid (GLA) rich cellular lipids. Especially, growth
      on tomato waste hydrolysate (TWH) yielded 17.6 g/l of biomass containing 39.6%
      oil and significant quantities of GLA corresponding to 800 mg/l GLA. Mycelium
      bounded proteolytic activity was detected during early growth stages on TWH and
      declined thereafter, increasing the concentration of assimilable nitrogen in the
      medium. However, addition of glucose in the medium during the stationary phase
      triggered the biosynthesis of reserve lipid, since an increase of the proportion
      of neutral lipids from 45% to 79% in total lipids was observed, while polar
      lipids decreased from 35% to 12% and from 20% to 9% for glycolipids plus
      sphingolipids and phospholipids, respectively.

PMID- 18609768
TI  - Japan wildlife boost.

PMID- 18609767
TI  - Worries grow over carbon emission goals.

PMID- 18609769
TI  - Ray Guillery.

PMID- 18609771
TI  - [Combination therapy: used too little and too late?].

PMID- 18609770
TI  - Acidic and alkaline bottom ash and composted manure blends as a  soil amendment.
AB  - Potential water quality impacts associated with using bottom ash (BA) and
      composted dairy manure (CM) as a soil amendment were evaluated in this study. Two
      column studies were conducted to evaluate three blends of acidic BA and CM
      (BA:CM, v/v) namely, B1ac (95:5), B2ac (90:10), and B3ac (80:20) and three blends
      of alkaline BA and CM (BA:CM, v/v), namely, B1al (95:5), B2al (90:10), and B3al
      (80:20) under constant head water table conditions. Samples from standing water
      (top) and leachate (bottom) were collected at weekly intervals until day 49 to
      evaluate the effects of different blend ratios and elapsed time on standing water
      and leachate chemical and physical properties. A higher CM content in both acidic
      and alkaline blends resulted in higher leachate concentrations for solids and
      nutrients tested in this study. Alkaline blends had higher standing water and
      leachate nutrients concentration compared to acidic blends. After day 28,
      standing water total dissolved solids (TDS) concentrations for all acidic blends
      was below the USEPA drinking water standard however, TDS value for alkaline blend
      was always below the standard. Similar trends were also observed for NO3-N and
      phosphorus (P) concentrations for both blends. Based on these findings, it was
      concluded that acidic and alkaline blends B1ac, B1al, B2ac and B2al may be
      considered as a soil amendment material.

PMID- 18609772
TI  - Hospital trusts failing to check inpatient's risk of deadly clots.

PMID- 18609773
TI  - Independent sector still struggling on data.

PMID- 18609774
TI  - End of postcode lottery could put PCTs in a spin.

PMID- 18609775
TI  - Sophia Christie on world class organisations.

PMID- 18609776
TI  - Quality has to bind the Darzi recipe for reform.

PMID- 18609777
TI  - Data briefing. The bottom line on new policies.

PMID- 18609778
TI  - On top of the world. World class commissioning.

PMID- 18609779
TI  - Richard Gleave on patients as consumers.

PMID- 18609780
TI  - Turnaround. Troubleshooter at the top.

PMID- 18609781
TI  - Raj Persaud on media hype.

PMID- 18609782
TI  - Equality. Boardroom demography.

PMID- 18609783
TI  - Auditors query PCT attempts to reduce last year's surplus.

PMID- 18609784
TI  - Managers face axe under new regime.

PMID- 18609786
TI  - Governors want more contact with the board.

PMID- 18609785
TI  - King's Fund urges polyclinic caution.

PMID- 18609787
TI  - Fewer deaths could mean more pay.

PMID- 18609788
TI  - Trusts face green targets in bid to cut carbon footprint.

PMID- 18609789
TI  - Hygiene code going unnoticed by most trusts.

PMID- 18609790
TI  - Academics slam two-tier legislation.

PMID- 18609791
TI  - King's Fund bursts the polyclinic plan bubble.

PMID- 18609792
TI  - Jon Restell on being at the birthday bash.

PMID- 18609793
TI  - Give old people a seat at the modernisation table.

PMID- 18609794
TI  - Data briefing. The birth of a new era in maternity.

PMID- 18609795
TI  - Just a pawn in the game.
AB  - Expert commentators fell politicians have consistently failed the NHS. Various
      governments have considered--and so far dismissed--schemes such as an NHS board
      to hive off awkward responsibilities. Underfunding drives the search for
      alternative systems, such as insurance--but no party has ever seriously
      considered abondoning the NHS.

PMID- 18609796
TI  - Needs assessment. A buzz of activity for local planners.

PMID- 18609797
TI  - HR workforce. Ever present.

PMID- 18609798
TI  - Commentaries. Orthodontic retention: a systematic review.

PMID- 18609799
TI  - [Automatic defibrillators: "Euphoria has subsided" (interview by Horst Gross)].

PMID- 18609800
TI  - [Dysphagia--the otolaryngologist's view].

PMID- 18609801
TI  - [Type 2 diabetes mellitus and obstructive sleep apnoea syndrome].

PMID- 18609802
TI  - [Patellar luxation].

PMID- 18609803
TI  - FOREWORD.

PMID- 18609805
TI  - SOME DISTURBANCES OF THE RHYTHM OF THE HEART.

PMID- 18609804
TI  - DIGITALIS IN HEART FAILURE WITH NORMAL RHYTHM.

PMID- 18609806
TI  - PRAECORDIAL LEADS IN ELECTROCARDIOGRAPHY.

PMID- 18609807
TI  - CHEST LEADS IN CLINICAL ELECTROCARDIOGRAPHY.

PMID- 18609808
TI  - A NEW SIGN OF LEFT VENTRICULAR FAILURE.

PMID- 18609809
TI  - THE SIGNIFICANCE OF ELECTROCARDIOGRAMS SHOWING A "SECOND POSITIVE WAVE OF QRS" IN
      LEAD III.

PMID- 18609810
TI  - SOME NOTES ON THE CARDIAC CLUB.

PMID- 18609811
TI  - THE NORMAL ELECTROCARDIOGRAM.

PMID- 18609812
TI  - PERSISTENT CONDUCTION DEFECTS FOLLOWING DIPHTHERIA.

PMID- 18609813
TI  - PAROXYSMAL TACHYCARDIA; AETIOLOGY AND PROGNOSIS OF ONE HUNDRED CASES.

PMID- 18609814
TI  - CHANGES IN THE CHEST LEAD ELECTROCARDIOGRAM IN CORONARY THROMBOSIS.

PMID- 18609815
TI  - TRAUMATIC ANEURYSM OF THE LEFT VENTRICLE.

PMID- 18609816
TI  - ANGINA PECTORIS FOLLOWING A CRUSHING ACCIDENT.

PMID- 18609817
TI  - A CASE OF MASSIVE HAEMOPERICARDIUM WITH RECOVERY AFTER PARACENTESIS.

PMID- 18609818
TI  - ALCOHOLIC BERI-BERI HEART.

PMID- 18609819
TI  - THE DRUG TREATMENT OF HYPERPIESIA.

PMID- 18609820
TI  - ELECTROCARDIOGRAPH ELECTROLYTES.

PMID- 18609821
TI  - SIR JAMES MACKENZIE'S HEART.

PMID- 18609822
TI  - CARDIAC MYXOMA A CLINICAL AND PATHOLOGICAL STUDY.

PMID- 18609823
TI  - STANDARDIZATION OF METHODS OF MEASURING THE ARTERIAL BLOOD PRESSURE: A JOINT
      REPORT OF THE COMMITTEES APPOINTED BY THE CARDIAC SOCIETY OF GREAT BRITAIN AND
      IRELAND AND THE AMERICAN HEART ASSOCIATION.

PMID- 18609824
TI  - THE EFFECT OF POTASSIUM ON THE HEART IN MAN.

PMID- 18609825
TI  - THE AETIOLOGY OF LUNG INFARCTION.

PMID- 18609826
TI  - HERPES ZOSTER AND ANGINA PECTORIS.

PMID- 18609827
TI  - SEX AND AGE FACTORS IN ACUTE AND CHRONIC VALVULAR DISEASE.

PMID- 18609828
TI  - STENOSIS AT THE LOWER BULBAR ORIFICE OF THE INFUNDIBULUM.

PMID- 18609829
TI  - VOLUMETRIC RECONSTRUCTION OF THE HEART IN HEALTH AND IN DISEASE: A RADIOLOGICAL
      STUDY.

PMID- 18609830
TI  - THE KINKED CAROTID ARTERY THAT SIMULATES ANEURYSM.

PMID- 18609831
TI  - ELECTROCARDIOGRAPHIC FINDINGS IN ANAEMIA.

PMID- 18609832
TI  - THE PSYCHOLOGICAL TREATMENT OF CASES WITH CARDIAC PAIN.

PMID- 18609833
TI  - ANALYSIS OF FIFTY NORMAL ELECTROCARDIOGRAMS INCLUDING LEAD IV.

PMID- 18609834
TI  - ELECTRICAL AXIS DEVIATION OF FIFTY NORMAL ELECTROCARDIOGRAMS.

PMID- 18609835
TI  - THE RELATIVE VALUE OF CERTAIN DIGITALIS PREPARATIONS IN HEART FAILURE WITH
      AURICULAR FIBRILLATION.

PMID- 18609836
TI  - U, THE SIXTH WAVE OF THE ELECTROCARDIOGRAM.

PMID- 18609837
TI  - THE P-R SEGMENT IN HYPERTENSIVE HEART DISEASE.

PMID- 18609838
TI  - THE SYNDROME OF SHORT P-R INTERVAL, APPARENT BUNDLE BRANCH BLOCK, AND ASSOCIATED
      PAROXYSMAL TACHYCARDIA.

PMID- 18609839
TI  - ATYPICAL PAIN IN ANGINA PECTORIS AND MYOCARDIAL INFARCTION.

PMID- 18609840
TI  - THE ACTION OF DIGITALIS IN HEART FAILURE WITH NORMAL RHYTHM.

PMID- 18609841
TI  - CONGENITAL ANEURYSMS OF ALL THREE SINUSES OF VALSALVA.

PMID- 18609843
TI  - THE ELECTROCARDIOGRAM IN PELLAGRA.

PMID- 18609842
TI  - A SINGLE CORONARY ARTERY.

PMID- 18609844
TI  - THE EFFECT OF ELECTRODES MADE OF DIFFERENT METALS ON THE SKIN CURRENTS.

PMID- 18609845
TI  - PERIPHERAL CIRCULATION BY PHOTO-ELECTRIC RECORDING.

PMID- 18609846
TI  - REGENERATION IN CARDIAC MUSCLE.

PMID- 18609847
TI  - TUBERCULOUS PERICARDITIS.

PMID- 18609848
TI  - RIGHT VENTRICULAR HYPERTROPHY OF UNKNOWN ORIGIN: SO-CALLED PULMONARY
      HYPERTENSION.

PMID- 18609850
TI  - FAILURE OF THE RIGHT VENTRICLE A CASE REPORT.

PMID- 18609849
TI  - PULMONARY HYPERTENSION.

PMID- 18609851
TI  - COARCTATION OF THE AORTA AT OR ABOVE THE ORIGIN OF THE LEFT SUBCLAVIAN ARTERY.

PMID- 18609852
TI  - PAROXYSMAL TACHYCARDIA CAUSED BY PENTAMETHYLENE-TETRAZOL.

PMID- 18609853
TI  - THE INFLUENCE OF FEAR ON THE ELECTROCARDIOGRAM.

PMID- 18609854
TI  - CARDIOVASCULAR DISTURBANCES CAUSED BY DEFICIENCY OF VITAMIN B(1).

PMID- 18609855
TI  - A CASE OF BERI-BERI HEART.

PMID- 18609856
TI  - PULMONARY STENOSIS PRODUCED BY ANEURYSM OF THE ASCENDING AORTA.

PMID- 18609857
TI  - ANEURYSMAL DILATATION OF THE PULMONARY ARTERY.

PMID- 18609858
TI  - A NOTE ON PULSATING MANUBRIAL TUMOUR.

PMID- 18609859
TI  - OESOPHAGEAL ELECTROCARDIOGRAMS IN AURICULAR FIBRILLATION.

PMID- 18609860
TI  - MYOCARDIAL AND PERICARDIAL LESIONS DUE TO NON-PENETRATING INJURY.

PMID- 18609861
TI  - THE VASCULAR RESPONSE IN CHRONIC RHEUMATOID ARTHRITIS.

PMID- 18609862
TI  - THE HEART RATE DURING A SIMPLE EXERCISE.

PMID- 18609863
TI  - WILLIAM WITHERING (1741-1799) AND EDGBASTON HALL.

PMID- 18609865
TI  - THE HISTORY OF MITRAL STENOSIS.

PMID- 18609866
TI  - CHEST LEAD CHANGES AS THE SOLE ELECTROCARDIOGRAPHIC EVIDENCE OF HEART DISEASE.

PMID- 18609867
TI  - PULMONARY EMBOLISM: DIAGNOSIS BY CHEST LEAD ELECTROCARDIOGRAPHY.

PMID- 18609868
TI  - T WAVE INVERSION, HEART SIZE, AND FUNCTIONAL CAPACITY: THE CORRELATION BETWEEN
      THESE IN 100 PATIENTS WITH HYPERTENSION.

PMID- 18609869
TI  - ATRIAL SEPTAL DEFECT.

PMID- 18609871
TI  - A COMPARISON OF THE MERCURIAL DIURETICS USED IN HEART FAILURE.

PMID- 18609870
TI  - ELECTROCARDIOGRAPHIC CHANGES AFTER ANOXAEMIA AND EXERCISE IN ANGINA OF EFFORT.

PMID- 18609872
TI  - COARCTATION OF THE AORTA WITH PATENT DUCTUS ARTERIOSUS.

PMID- 18609873
TI  - A FATAL CASE OF MYOCARDIAL CONTUSION.

PMID- 18609874
TI  - RUPTURED AORTIC VALVE WITH MYCOTIC ANEURYSM DUE TO ACUTE BACTERIAL ENDOCARDITIS.

PMID- 18609875
TI  - MAUDE ABBOTT.

PMID- 18609876
TI  - KAREL FREDERIK WENCKEBACH.

PMID- 18609877
TI  - VARIABLE VENTRICULAR COMPLEXES IN HEART BLOCK, AND THEIR RELATION TO BILATERAL
      BUNDLE BRANCH BLOCK.

PMID- 18609878
TI  - HYDROTHORAX IN HEART FAILURE.

PMID- 18609879
TI  - CHARLES LAUBRY.

PMID- 18609880
TI  - TRICUSPID STENOSIS; WITH PARTICULAR REFERENCE TO DIAGNOSIS AND PROGNOSIS.

PMID- 18609881
TI  - IDIOPATHIC CYSTIC MEDIAL NECROSIS OF THE AORTA.

PMID- 18609882
TI  - THE ELECTROCARDIOGRAM OF THE STOKES-ADAMS ATTACK.

PMID- 18609883
TI  - TOTAL THYROIDECTOMY FOR HEART FAILURE: AN UNUSUAL CASE.

PMID- 18609884
TI  - COARCTATION OF THE AORTA: THE COLLATERAL CIRCULATION.

PMID- 18609885
TI  - CHANGES IN RENAL FUNCTION AND PERSISTENCE OF THE MURMUR AFTER LIGATURE OF A
      PATENT DUCTUS ARTERIOSUS.

PMID- 18609886
TI  - INVERSION OF THE T WAVES IN LEAD II CAUSED BY A VARIATION IN POSITION OF THE
      HEART.

PMID- 18609887
TI  - PULMONARY VENOUS RETURN VIA THE SUPERIOR VENA CAVA.

PMID- 18609888
TI  - CHEST LEAD (CR(1)) ELECTROCARDIOGRAMS IN AURICULAR FIBRILLATION.

PMID- 18609889
TI  - PROCEEDINGS OF THE CARDIAC SOCIETY OF GREAT BRITAIN AND IRELAND.

PMID- 18609890
TI  - INTRACARDIAC TUMOURS.

PMID- 18609891
TI  - GRAHAM STEELL.

PMID- 18609892
TI  - A CURIOUS SYNDROME, WITH SIGNS SUGGESTING CERVICAL ARTERIO-VENOUS FISTULA, AND
      THE PULSES OF NECK AND ARMS LOST.

PMID- 18609893
TI  - THE CONDUCTING SYSTEM OF THE VERTEBRATE HEART.

PMID- 18609894
TI  - THE SINO-AURICULAR NODE: A HISTORICAL NOTE.

PMID- 18609895
TI  - CHEST LEADS IN CONGENITAL AND ACQUIRED DEXTROCARDIA.

PMID- 18609896
TI  - ELECTROCARDIOGRAPHIC CHANGES DUE TO TRAUMA.

PMID- 18609897
TI  - THE ELECTROCARDIOGRAM IN FRIEDREICH DISEASE.

PMID- 18609899
TI  - CONGENITAL PULMONARY ATRESIA WITH CEREBRAL THROMBOSIS AND HEMIPLEGIA.

PMID- 18609898
TI  - HEMIPLEGIA IN CYANOTIC CONGENITAL HEART DISEASE.

PMID- 18609900
TI  - PARTIAL HEART BLOCK DUE TO DIGITALIS.

PMID- 18609901
TI  - BLOOD PRESSURE AND OLD AGE.

PMID- 18609902
TI  - TRANSIENT INVERTED T WAVES AFTER PAROXYSMAL TACHYCARDIA.

PMID- 18609903
TI  - PROGNOSIS IN PAROXYSMAL TACHYCARDIA AND PAROXYSMAL AURICULAR FIBRILLATION.

PMID- 18609904
TI  - FAINTING AND FITS IN CARDIAC INFARCTION.

PMID- 18609905
TI  - PROCEEDINGS OF THE CARDIAC SOCIETY OF GREAT BRITAIN AND IRELAND.

PMID- 18609906
TI  - TWO CASES OF DIGITALIS POISONING.

PMID- 18609907
TI  - CONGENITAL PULMONARY STENOSIS WITH LEFT VENTRICULAR ENLARGEMENT ASSOCIATED WITH
      ATRIAL SEPTAL DEFECT.

PMID- 18609908
TI  - INFARCTION OF THE CARDIAC AURICLES (ATRIA): CLINICAL, PATHOLOGICAL, AND
      EXPERIMENTAL STUDIES.

PMID- 18609909
TI  - PROGNOSIS OF RIGHT BUNDLE BRANCH BLOCK: A STUDY OF 104 CASES.

PMID- 18609910
TI  - DR. SAMUEL JOHNSON: HIS MEDICAL HISTORY AS RECORDED BY JAMES BOSWELL.

PMID- 18609911
TI  - INVERSION OF T WAVES AFTER LONG PAROXYSMS OF TACHYCARDIA.

PMID- 18609913
TI  - CARDIAC SYNDROMES COMPLICATING DIABETES AND THEIR TREATMENT.

PMID- 18609912
TI  - CONGENITAL HEART BLOCK: REPORT OF A CASE.

PMID- 18609914
TI  - CONGENITAL HEART BLOCK WITH ATRIAL AND VENTRICULAR SEPTAL DEFECT.

PMID- 18609915
TI  - CONGENITAL COMPLETE HEART BLOCK.

PMID- 18609916
TI  - TUBERCULOUS PERICARDIAL EFFUSION.

PMID- 18609918
TI  - ELECTROCARDIOGRAPHIC PATTERNS OF COMBINED VENTRICULAR STRAIN.

PMID- 18609917
TI  - SIGNS SIMULATING THOSE OF MITRAL STENOSIS.

PMID- 18609920
TI  - PAROXYSMAL VENTRICULAR TACHYCARDIA.

PMID- 18609921
TI  - PARTIAL HEART BLOCK WITH DROPPED BEATS.

PMID- 18609922
TI  - THE REFERENCE OF CARDIAC PAIN TO A PHANTOM LEFT ARM.

PMID- 18609923
TI  - CONGENITAL HEART BLOCK WITH DEXTROCARDIA.

PMID- 18609924
TI  - FATAL CORONARY THROMBOSIS IN A MAN AGED TWENTY-TWO.

PMID- 18609926
TI  - CHEST LEAD CR(7) IN CARDIAC INFARCTION.

PMID- 18609925
TI  - SYPHILITIC ANGINA PECTORIS.

PMID- 18609927
TI  - POTASSIUM EFFECTS ON T WAVE INVERSION IN MYOCARDIAL INFARCTION AND PREPONDERANCE
      OF A VENTRICLE.

PMID- 18609928
TI  - POTASSIUM EFFECTS ON THE ELECTROCARDIOGRAM OF THYROID DEFICIENCY.

PMID- 18609929
TI  - ANGINAL PAIN IN MYXOEDEMA.

PMID- 18609930
TI  - COMMON AORTO-PULMONARY TRUNK: A RARE CONGENITAL DEFECT.

PMID- 18609931
TI  - BACTERIAL ANEURYSM.

PMID- 18609932
TI  - HEART CHANGES IN ALKALOSIS.

PMID- 18609934
TI  - A CASE OF SUBENDOCARDIAL INFARCTION.

PMID- 18609933
TI  - EFFECTS OF PLASMOQUIN, ATEBRIN, AND QUININE ON THE ELECTROCARDIOGRAM.

PMID- 18609935
TI  - EXTREME CARDIAC HYPERTROPHY REPORT OF TWO CASES WITH AORTIC HYPOPLASIA AND
      ENDOCRINE DISORDERS.

PMID- 18609936
TI  - EISENMENGER'S COMPLEX.

PMID- 18609937
TI  - CASUAL AND BASAL BLOOD PRESSURES I.-IN BRITISH AND EGYPTIAN MEN.

PMID- 18609938
TI  - CASUAL AND BASAL BLOOD PRESSURES II.-IN ESSENTIAL HYPERTENSION.

PMID- 18609940
TI  - LATENT HEART BLOCK.

PMID- 18609939
TI  - CASUAL AND BASAL BLOOD PRESSURES III.-IN RENAL HYPERTENSION.

PMID- 18609941
TI  - AURICULAR FIBRILLATION LATE IN THE COURSE OF DIPHTHERIA.

PMID- 18609942
TI  - COMPLETE AURICULO-VENTRICULAR DISSOCIATION WITH HIGH VENTRICULAR RATE IN
      PAROXYSMAL TACHYCARDIA.

PMID- 18609943
TI  - PERSISTENT TRUNCUS ARTERIOSUS.

PMID- 18609944
TI  - COARCTATION OF THE AORTA, DOUBLE MITRAL A-V ORIFICE, AND LEAKING CEREBRAL
      ANEURYSM.

PMID- 18609945
TI  - TRIPLE HEART RHYTHM.

PMID- 18609947
TI  - PROCEEDINGS OF THE CARDIAC SOCIETY OF GREAT BRITAIN AND IRELAND.

PMID- 18609946
TI  - TREATMENT OF SUBACUTE INFECTIVE ENDOCARDITIS WITH HEPARIN AND CHEMOTHERAPY.

PMID- 18609948
TI  - ADRENAL-SYMPATHETIC SYNDROME: CHROMAFFIN TISSUE TUMOUR WITH PAROXYSMAL
      HYPERTENSION.

PMID- 18609949
TI  - RECIPROCAL BEATING INITIATED BY VENTRICULAR PREMATURE SYSTOLES.

PMID- 18609950
TI  - HEART FAILURE IN THE AGED.

PMID- 18609951
TI  - A CASE OF MYXOMA OF THE LEFT AURICLE.

PMID- 18609952
TI  - CIRCULATORY FAILURE DUE TO VITAMIN B DEFICIENCY.

PMID- 18609954
TI  - THE HEART IN MYOTONIA ATROPHICA.

PMID- 18609953
TI  - CARDIAC OUTPUT IN MAN BY A DIRECT FICK METHOD: Effects of Posture, Venous
      Pressure Change, Atropine, And Adrenaline.

PMID- 18609955
TI  - SYNCHRONOUS HEART SOUND RECORDING BY APPLICATION OF A SECOND CHANNEL TO THE
      COSSORROBERTSON CARDIOGRAPH.

PMID- 18609956
TI  - SOCIAL AND ECONOMIC CONDITIONS AND THE INCIDENCE OF RHEUMATIC HEART DISEASE.

PMID- 18609957
TI  - UNUSUAL ELECTROCARDIOGRAM IN DEXTROCARDIA.

PMID- 18609958
TI  - AURICULO-VENTRICULAR RHYTHM.

PMID- 18609959
TI  - PAROXYSMAL HEART BLOCK AND VENTRICULAR STANDSTILL.

PMID- 18609960
TI  - HEART BLOCK WITH ANEURYSM OF THE AORTIC SINUS.

PMID- 18609961
TI  - STOKES-ADAMS ATTACKS IN A CHILD.

PMID- 18609963
TI  - A RARE CASE OF COMPLETE HEART BLOCK.

PMID- 18609962
TI  - COMPLETE HEART BLOCK.

PMID- 18609964
TI  - FREDERICK JOHN POYNTON.

PMID- 18609965
TI  - THE CARE OF RHEUMATIC CHILDREN: REPORT BY THE CARDIAC SOCIETY AND BRITISH
      PAEDIATRIC ASSOCIATION.

PMID- 18609967
TI  - ACUTE LEFT AURICULAR FAILURE.

PMID- 18609966
TI  - MYOCARDIAL INFARCTION.

PMID- 18609968
TI  - CARDIAC INVOLVEMENT IN SPIROCHAETAL JAUNDICE.

PMID- 18609969
TI  - INCOMPLETE BUNDLE BRANCH BLOCK.

PMID- 18609970
TI  - THE PLACE OF FOLIANDRIN WITHIN THE GROUP OF CARDIAC GLUCOSIDES.

PMID- 18609971
TI  - TEMPORAL ARTERITIS.

PMID- 18609972
TI  - NICOTINIC ACID IN THE TREATMENT OF ANGINA PECTORIS.

PMID- 18609973
TI  - PULMONARY EMBOLISM: THE CLINICAL AND CARDIOGRAPHIC PROGRESS OF A CASE.

PMID- 18609974
TI  - CONGENITAL PERICARDIAL DEFECTS.

PMID- 18609975
TI  - CASUAL AND BASAL BLOOD PRESSURES IV. THEIR RELATIONSHIP TO THE SUPPLEMENTAL
      PRESSURE WITH A NOTE ON STATISTICAL IMPLICATIONS.

PMID- 18609976
TI  - MYOCARDIAL INFARCTION.

PMID- 18609977
TI  - A CASE OF TUBERCULOUS PERICARDITIS.

PMID- 18609979
TI  - CARDIO-AORTIC FISTULA.

PMID- 18609978
TI  - PERFORATION OF THE INTERVENTRICULAR SEPTUM DUE TO CARDIAC INFARCTION.

PMID- 18609980
TI  - MERCURIAL DIURETICS: THE ADDITION OF MAGNESIUM SULPHATE TO PREVENT THE TOXIC
      EFFECTS OF THEIR INTRAVENOUS ADMINISTRATION.

PMID- 18609981
TI  - CLINICAL EVALUATION OF THE PRESSOR ACTIVITY OF METHEDRINE, NEO-SYNEPHRINE,
      PAREDRINE, AND PHOLEDRINE.

PMID- 18609982
TI  - THE UNITY OF PAROXYSMAL TACHYCARDIA AND AURICULAR FLUTTER.

PMID- 18609983
TI  - CHEST LEADS FOR THE DEMONSTRATION OF AURICULAR ACTIVITY.

PMID- 18609984
TI  - PROCEEDINGS OF THE CARDIAC SOCIETY OF GREAT BRITAIN AND IRELAND.

PMID- 18609985
TI  - PATENT DUCTUS ARTERIOSUS AND ITS SURGICAL TREATMENT.

PMID- 18609986
TI  - CARDIAC MANIFESTATIONS IN A CASE OF TUBEROUS SCLEROSIS.

PMID- 18609987
TI  - COR TRILOCULARE BIAURICULARE: AN UNUSUAL ADULT HEART.

PMID- 18609988
TI  - AN UNUSUAL CASE OF A-V NODAL RHYTHM WITH VARYING A-V BLOCK.

PMID- 18609989
TI  - PERICARDITIS AND COMPLETE HEART BLOCK DURING THIOURACIL THERAPY.

PMID- 18609990
TI  - ADVANCED MITRAL STENOSIS AT THREE YEARS OLD.

PMID- 18609991
TI  - MORPHINE HYPERSENSITIVITY IN KYPHOSCOLIOSIS.

PMID- 18609992
TI  - TRANSIENT HEART BLOCK AND CORONARY OCCLUSION IN PLEURAL SHOCK.

PMID- 18609993
TI  - HEART BLOCK FOLLOWING DIPHTHERIA.

PMID- 18609994
TI  - AURICULAR FIBRILLATION AND AURICULAR FLUTTER IN DIPHTHERIA.

PMID- 18609995
TI  - HEART BLOCK AND THE SIMULATION OF BUNDLE BLOCK IN DIPHTHERIA.

PMID- 18609996
TI  - ELECTROCARDIOGRAPHIC CHANGES AND THE EFFECT OF NIACIN THERAPY IN PELLAGRA.

PMID- 18609998
TI  - SINUS BRADYCARDIA WITH CARDIAC ASYSTOLE.

PMID- 18609997
TI  - BLOOD VOLUME DETERMINATIONS WITH RADIOACTIVE PHOSPHORUS.

PMID- 18609999
TI  - LIGATURE OF PATENT DUCTUS ARTERIOSUS.

PMID- 18610000
TI  - LIGATION OF THE PATENT DUCTUS ARTERIOSUS.

PMID- 18610001
TI  - PAROXYSMAL TACHYCARDIA IN INFANCY AND CHILDHOOD.

PMID- 18610002
TI  - TRAUMATIC RUPTURE OF THE INTERVENTRICULAR SEPTUM.

PMID- 18610003
TI  - MULTIPLE CHEST LEAD CARDIOGRAMS AND THEIR CLINICAL VALUE.

PMID- 18610004
TI  - HEART BLOCK IN A DIABETIC WITH ONLY MILD ARTERIOSCLEROSIS.

PMID- 18610005
TI  - ARTERIAL THICKENING IN OLD AGE.

PMID- 18610006
TI  - MALIGNANT HYPERTENSION CURED BY UNILATERAL NEPHRECTOMY.

PMID- 18610007
TI  - CARDIAC OUTPUT IN A CASE OF PERICARDIAL EFFUSION: WITH A NOTE ON PERICARDIAL
      PAIN.

PMID- 18610008
TI  - TUBERCULOUS PERICARDITIS WITH EFFUSION.

PMID- 18610009
TI  - MERCURIAL DIURETICS: INTOLERANCE AS SHOWN BY SKIN SENSITIVITY.

PMID- 18610011
TI  - THE CAROTID SHUDDER.

PMID- 18610010
TI  - THE EFFECTS OF EMETINE ON THE HEART.

PMID- 18610012
TI  - A QUANTITATIVE ELECTROCARDIOGRAPHIC METHOD.

PMID- 18610013
TI  - A CASE OF MYXOMA OF THE HEART.

PMID- 18610014
TI  - PAROXYSMAL TACHYCARDIA AND 2: 1 HEART BLOCK.

PMID- 18610016
TI  - WILLIAM RITCHIE.

PMID- 18610017
TI  - PROCEEDINGS OF THE CARDIAC SOCIETY OF GREAT BRITAIN AND IRELAND.

PMID- 18610015
TI  - IMMERSION AS A FACTOR IN THE DEVELOPMENT OF HYPERTENSION.

PMID- 18610019
TI  - HYPOXAEMIA TESTS IN CORONARY DISEASE.

PMID- 18610018
TI  - THOMAS LEWIS.

PMID- 18610020
TI  - MYXOEDEMA WITH PERICARDIAL EFFUSION.

PMID- 18610021
TI  - ANGINA PECTORIS WITH ASSOCIATED LEFT PAROXYSMAL PTOSIS.

PMID- 18610022
TI  - INDUCED CHANGES IN THE CIRCULATION IN CONSTRICTIVE PERICARDITIS.

PMID- 18610023
TI  - PARAVERTEBRAL BLOCK AND THE ELECTROCARDIOGRAM IN ANGINA PECTORIS.

PMID- 18610024
TI  - THE MECHANISM OF THE WENCKEBACH TYPE OF A-V BLOCK.

PMID- 18610027
TI  - CARDIOVASCULAR DISEASES IN THE BRITISH ARMY OVERSEAS.

PMID- 18610026
TI  - POSTURAL HYPOTENSION.

PMID- 18610028
TI  - ELECTROCARDIOGRAPHIC ABNORMALITIES IN SEVERE MALNUTRITION.

PMID- 18610029
TI  - THE EFFECT OF NITRITE AND EXERCISE ON THE INVERTED T WAVE.

PMID- 18610030
TI  - AURICULAR PREMATURE SYSTOLES: THE DURATION OF THE ELECTRICAL SYSTOLE.

PMID- 18610031
TI  - PULMONARY VASCULAR SCLEROSIS WITH RIGHT VENTRICULAR FAILURE.

PMID- 18610032
TI  - PRAECORDIAL ELECTROCARDIOGRAMS: A COMPARISON OF CF AND V LEAD CONNECTIONS.

PMID- 18610033
TI  - BILHARZIAL HEART DISEASE IN EGYPT: COR PULMONALE DUE TO BILHARZIAL PULMONARY
      ENDARTERITIS.

PMID- 18610034
TI  - MECHANISM OF THE WOLFF-PARKINSON-WHITE SYNDROME.

PMID- 18610035
TI  - THE ACTION OF MAGNESIUM ON THE HEART.

PMID- 18610036
TI  - RUPTURED CONGENITAL ANEURYSM OF THE POSTERIOR SINUS OF VALSALVA.

PMID- 18610038
TI  - SILENT DISSECTION OF THE AORTA.

PMID- 18610037
TI  - HEALED DISSECTING ANEURYSM.

PMID- 18610039
TI  - THE GENESIS OF THE NORMAL ELECTROCARDIOGRAM.

PMID- 18610040
TI  - HEART-VECTOR AND LEADS.

PMID- 18610041
TI  - THE HEART IN STERNAL DEPRESSION.

PMID- 18610042
TI  - AMMI VISNAGA IN THE TREATMENT OF THE ANGINAL SYNDROME.

PMID- 18610043
TI  - PREMATURE SYSTOLES ORIGINATING IN THE SINO-AURICULAR NODE.

PMID- 18610045
TI  - CHRONIC DISSECTING ANEURYSMS.

PMID- 18610044
TI  - DISSECTING ANEURYSM OF THE AORTA, WITH CARDIOGRAMS SUGGESTIVE OF CARDIAC
      INFARCTION.

PMID- 18610046
TI  - DISSECTING ANEURYSM WITH SURVIVAL FOR THREE MONTHS AFTER RUPTURE INTO THE PLEURA.

PMID- 18610047
TI  - DISSECTING ANEURYSM OF THE AORTA: A NEW SIGN.

PMID- 18610048
TI  - ANEURYSMAL DILATATION OF THE LEFT AURICLE WITH EROSION OF THE SPINE.

PMID- 18610050
TI  - PROCEEDINGS OF THE CARDIAC SOCIETY OF GREAT BRITAIN AND IRELAND.

PMID- 18610049
TI  - EARLY DIAGNOSIS OF RHEUMATIC VALVULAR DISEASE IN RECRUITS.

PMID- 18610051
TI  - HEART MURMURS PART I.

PMID- 18610052
TI  - PHONOCARDIOGRAMS OF AURICULAR MURMURS FROM A CASE WITH MITRAL STENOSIS AND HEART
      BLOCK.

PMID- 18610053
TI  - CHRONIC AURICULAR TACHYCARDIA.

PMID- 18610055
TI  - CONGENITAL HEART DISEASE WITH ISOLATED INVERSION OF THE ABDOMINAL VISCERA.

PMID- 18610056
TI  - SUBACUTE BACTERIAL ENDOCARDITIS WITH ONSET AS OPTIC NEURITIS.

PMID- 18610057
TI  - PENICILLIN TREATMENT OF SUBACUTE BACTERIAL ENDOCARDITIS.

PMID- 18610058
TI  - INFECTIVE ENDOCARDITIS OF THE TRICUSPID VALVE: REPORT OF A CASE DUE TO
      STREPTOCOCCUS VIRIDANS.

PMID- 18610059
TI  - COARCTATION OF THE AORTA: II. CLINICAL FEATURES.

PMID- 18610060
TI  - THE HEART IN TOXAEMIA OF PREGNANCY.

PMID- 18610061
TI  - CHARLES HERAPATH.

PMID- 18610062
TI  - PAROXYSMAL TACHYCARDIA FOLLOWED BY TEMPORARY INVERSION OF THE T WAVES.

PMID- 18610063
TI  - THE EFFECT OF DEMEROL, ERGOTAMINE, AND DIHYDRO-ERGOTAMINE ON MORTALITY AFTER
      CORONARY OCCLUSION IN DOGS.

PMID- 18610065
TI  - THOMAS WARDROP GRIFFITH.

PMID- 18610064
TI  - UNUSUAL LONGEVITY IN ANEURYSM OF THE THORACIC AORTA.

PMID- 18610066
TI  - ELECTROCARDIOGRAPHIC STUDY OF TYPHOID MYOCARDITIS.

PMID- 18610067
TI  - HEART-VECTOR AND LEADS. Part II.

PMID- 18610068
TI  - IDIOPATHIC CARDIAC HYPERTROPHY.

PMID- 18610069
TI  - THE HEART IN SCLERODERMA.

PMID- 18610070
TI  - TESTICULAR TERATOMA WITH EXTENSIVE INTRACARDIAC METASTASES.

PMID- 18610071
TI  - ERGOTAMINE AND APPARENT CORONARY INSUFFICIENCY.

PMID- 18610073
TI  - MYOCARDIAL TUBERCULOSIS WITH PAROXYSMAL VENTRICULAR TACHYCARDIA.

PMID- 18610072
TI  - COARCTATION OF THE AORTA.

PMID- 18610074
TI  - HEART MURMURS PART II.

PMID- 18610075
TI  - REPETITIVE PAROXYSMAL TACHYCARDIA.

PMID- 18610076
TI  - A CASE OF PERFORATED DUODENAL ULCER AND CARDIAC INFARCTION.

PMID- 18610077
TI  - PAROXYSMAL HEART BLOCK IN BUNDLE BRANCH BLOCK.

PMID- 18610078
TI  - THE FIRST HEART SOUND IN AURICULAR AND VENTRICULAR EXTRASYSTOLES.

PMID- 18610079
TI  - THE PROGNOSIS OF PATENT DUCTUS ARTERIOSUS.

PMID- 18610080
TI  - CARDIAC CATHETERIZATION IN CASES OF PATENT INTERAURICULAR SEPTUM, PRIMARY
      PULMONARY HYPERTENSION, FALLOT'S TETRALOGY, AND PULMONARY STENOSIS.

PMID- 18610081
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610082
TI  - PROCEEDINGS OF THE INTERNATIONAL CONFERENCE OF PHYSICIANS.

PMID- 18610083
TI  - TWO CASES OF TEMPORAL ARTERITIS: ONE WITH ANGINA OF EFFORT.

PMID- 18610084
TI  - HYPERTENSION DUE TO SYPHILITIC OCCLUSION OF THE MAIN RENAL ARTERIES.

PMID- 18610085
TI  - BALL THROMBUS OF THE HEART.

PMID- 18610086
TI  - MASS THROMBUS OF THE LEFT AURICLE.

PMID- 18610087
TI  - ANGINA IN WOMEN.

PMID- 18610088
TI  - THE VARIATION OF CASUAL, BASAL, AND SUPPLEMENTAL BLOOD PRESSURES IN HEALTH AND IN
      ESSENTIAL HYPERTENSION.

PMID- 18610089
TI  - CARDIOVASCULAR CHANGES FOLLOWING ELECTRO-CONVULSIVE THERAPY.

PMID- 18610090
TI  - CLINICAL VALUE OF UNIPOLAR CHEST AND LIMB LEADS.

PMID- 18610091
TI  - JOHN COWAN.

PMID- 18610092
TI  - RAPID DIGITALIZATION.

PMID- 18610093
TI  - THE RELATIVE VALUE OF DIGITALINE PREPARATIONS IN HEART FAILURE WITH AURICULAR
      FIBRILLATION.

PMID- 18610094
TI  - THE HEART IN RHEUMATOID ARTHRITIS.

PMID- 18610095
TI  - THE SURGERY OF CONGENITAL HEART DISEASE.

PMID- 18610096
TI  - PULMONARY HEART DISEASE ACUTE AND CHRONIC.

PMID- 18610097
TI  - THE CLINICAL VALUE OF CHEST LEADS.

PMID- 18610098
TI  - THE USE OF THE PHONOCARDIOGRAPH IN CLINICAL CARDIOLOGY.

PMID- 18610099
TI  - SHORTER COMMUNICATIONS.

PMID- 18610100
TI  - PATHOGENESIS OF LEFT BUNDLE BRANCH BLOCK.

PMID- 18610101
TI  - EROSION OF RIBS IN COARCTATION OF THE AORTA A NOTE ON THE HISTORY OF A
      PATHOGNOMIC SIGN.

PMID- 18610102
TI  - COARCTATION OF THE AORTA REVIEW OF TWENTY-THREE SERVICE CASES.

PMID- 18610103
TI  - THE RIGHT PRAECORDIAL LEAD.

PMID- 18610104
TI  - CORONARY ARTERY ANEURYSM WITH OCCLUSION DUE TO A CALCIFIED THROMBUS.

PMID- 18610105
TI  - HEART BLOCK IN OSTEITIS DEFORMANS.

PMID- 18610106
TI  - VENTRICULAR COMPLEXES IN HEART BLOCK.

PMID- 18610107
TI  - THE REGENERATIVE CAPACITY OF MAMMALIAN HEART MUSCLE.

PMID- 18610108
TI  - INCIPIENT SYMMETRICAL PERIPHERAL GANGRENE COMPLICATING PAROXYSMAL TACHYCARDIA.

PMID- 18610109
TI  - TUBERCULOUS PERICARDITIS.

PMID- 18610110
TI  - EUROPAN CARDIOLOGICAL SOCIETY.

PMID- 18610111
TI  - SOCIETE EUROPEENNE DE CARDIOLOGIE.

PMID- 18610112
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610114
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610113
TI  - WILLIAM WITHERING.

PMID- 18610115
TI  - Erratum.
AB  - [This corrects the article on p. 315 in vol. 12.].

PMID- 18610116
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610117
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610118
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610119
TI  - EUROPEAN CONGRESS OF CARDIOLOGY.

PMID- 18610120
TI  - Erratum.
AB  - [This corrects the article on p. 116 in vol. 14.].

PMID- 18610121
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610122
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610123
TI  - JENNER HOSKIN.

PMID- 18610124
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610125
TI  - BASIL T. PARSONS-SMITH.

PMID- 18610126
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610127
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610128
TI  - SECOND EUROPEAN CONGRESS OF CARDIOLOGY.

PMID- 18610129
TI  - EDITORIAL COMMENT.

PMID- 18610130
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610131
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610132
TI  - THE CLINICAL USES OF OXIMETRY.

PMID- 18610133
TI  - PROPERTIES AND BIOLOGICAL BEHAVIOUR OF COOMASSIE BLUE.

PMID- 18610135
TI  - THE PATHOGENESIS OF INFARCTION OF THE RIGHT VENTRICLE.

PMID- 18610134
TI  - CLINICAL APPLICATIONS OF COOMASSIE BLUE.

PMID- 18610136
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610138
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610137
TI  - PREDNISOLONE MAINTENANCE THERAPY IN CHRONIC PULMONARY HEART DISEASE.

PMID- 18610139
TI  - DISSECTING ANEURYSM OF THE CORONARY ARTERY IN ARACHNODACTYLY.

PMID- 18610140
TI  - RIGHT VENTRICULAR PRESSURE CURVES IN CONGENITAL AND ACQUIRED HEART DISEASE.

PMID- 18610141
TI  - HAEMODYNAMIC STUDIES IN HIGH OUTPUT BERI-BERI.

PMID- 18610142
TI  - THE EFFECT OF HYPOTHERMIA ON ATRIAL FIBRILLATION AND OTHER ARRHYTHMIAS.

PMID- 18610144
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610145
TI  - SPONTANEOUS RUPTURE OF A PAPILLARY MUSCLE OF THE HEART.

PMID- 18610143
TI  - THE PHONOCARDIOGRAM IN ENDOMYOCARDIAL FIBROSIS.

PMID- 18610146
TI  - ELECTROCARDIOGRAPHIC AND RADIOLOGICAL STUDIES IN HIATUS HERNIA.

PMID- 18610147
TI  - GOUT IN CYANOTIC CONGENITAL HEART DISEASE.

PMID- 18610149
TI  - THE DESIGN OF A CARDIAC DEFIBRILLATOR.

PMID- 18610148
TI  - A CURRENT CONCEPT OF THE REGULATION OF BLOOD VOLUME.

PMID- 18610150
TI  - CARDIOLOGICAL OBSERVATIONS AT THE SIXTH BRITISH EMPIRE AND COMMONWEALTH GAMES.

PMID- 18610152
TI  - THE THIRD EUROPEAN CONGRESS OF CARDIOLOGY.

PMID- 18610151
TI  - ENDOCARDIAL THICKENING ASSOCIATED WITH DISEASED VALVES.

PMID- 18610153
TI  - CHARLES LAUBRY 1872-1960.

PMID- 18610154
TI  - CALCIFICATION OF THE MYOCARDIUM OF A YOUNG WOMAN.

PMID- 18610155
TI  - AN UNUSUAL ATRIAL RHYTHM WITH VARYING A-V BLOCK.

PMID- 18610156
TI  - SERUM LACTIC DEHYDROGENASE ESTIMATIONS IN MYOCARDIAL INFARCTION.

PMID- 18610157
TI  - THE SURGICAL TREATMENT OF PULMONARY STENOSIS.

PMID- 18610158
TI  - A COMPARISON OF MEDICAL AND SURGICAL TREATMENT OF MITRAL STENOSIS.

PMID- 18610159
TI  - CLINICAL AND HAEMODYNAMIC PATTERNS IN ENDOMYOCARDIAL FIBROSIS.

PMID- 18610160
TI  - EUROPEAN SOCIETIES OF CARDIOLOGY.

PMID- 18610161
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610162
TI  - ISOLATED MYOCARDITIS OF THE RIGHT VENTRICLE.

PMID- 18610163
TI  - VENTRICULAR PREMATURE BEATS IN THE DIAGNOSIS OF MYOCARDIAL INFARCTION.

PMID- 18610164
TI  - ATRIAL SEPTAL DEFECT WITH PULMONARY HYPERTENSION.

PMID- 18610166
TI  - J. S. HALDANE CENTENARY, 1961.

PMID- 18610165
TI  - PERCUTANEOUS PUNCTURE OF THE LEFT VENTRICLE.

PMID- 18610167
TI  - F. G. HOBSON.

PMID- 18610168
TI  - GUSTAV NYLIN.

PMID- 18610169
TI  - EVOLUTION OF GRAPHIC SYMBOLS FOR CARDIOVASCULAR SOUNDS AND MURMURS.

PMID- 18610170
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610171
TI  - COR BILOCULARE.

PMID- 18610172
TI  - Erratum.
AB  - [This corrects the article on p. ADV in vol. XXIII.].

PMID- 18610173
TI  - IN DEFENCE OF THE INTRINSIC DEFLECTION.

PMID- 18610174
TI  - COMPLETE TRANSPOSITION OF THE GREAT VESSELS.

PMID- 18610175
TI  - STUDY OF THE KIDNEY IN THE BANTU WITH HYPERTENSION.

PMID- 18610176
TI  - HAEMODYNAMICS IN MITRAL STENOSIS BEFORE, DURING, AND AFTER VALVOTOMY.

PMID- 18610177
TI  - CARDIOGRAPHIC ASSESSMENT OF PULMONARY VASCULAR DISEASE IN VENTRICULAR SEPTAL
      DEFECT.

PMID- 18610178
TI  - COMBINED MITRAL AND AORTIC STENOSIS.

PMID- 18610179
TI  - THE EARLY DESCRIPTIONS OF AORTIC INCOMPETENCE.

PMID- 18610180
TI  - INDICATOR DILUTION CURVES IN MITRAL VALVULAR DISEASE.

PMID- 18610181
TI  - THE BRITISH CARDIAC SOCIETY AND THE CARDIAC CLUB: 1922-1961.

PMID- 18610182
TI  - DIFFUSE ARTERIOPATHY.

PMID- 18610184
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610183
TI  - A CORONARY PROGNOSTIC INDEX FOR GRADING THE SEVERITY OF INFARCTION.

PMID- 18610185
TI  - RIGHT ATRIAL MYXOMA MISTAKEN FOR CONSTRICTIVE PERICARDITIS.

PMID- 18610186
TI  - THE RELATION BETWEEN MYOCARDIAL LESIONS AND CORONARY ARTERY DISEASE II. A
      SELECTED GROUP OF PATIENTS WITH MASSIVE CARDIAC NECROSIS OR SCARRING.

PMID- 18610187
TI  - VALVOTOMY IN MITRAL STENOSIS WITH EXTREME PULMONARY VASCULAR RESISTANCE.

PMID- 18610188
TI  - COR TRILOCULARE BIATRIATUM.

PMID- 18610189
TI  - AN AMPEROMETRIC TECHNIQUE FOR RECORDING ASCORBATE DILUTION CURVES AND BLOOD FLOW
      PULSES.

PMID- 18610190
TI  - VENTRICULAR ENDOMYOCARDIAL CHANGES AFTER IMPAIRMENT OF CARDIAC LYMPH FLOW IN
      DOGS.

PMID- 18610191
TI  - THE FOURTH WORLD CONGRESS OF CARDIOLOGY.

PMID- 18610192
TI  - ELECTROCARDIOGRAPHIC CHANGES AT HIGH ALTITUDE.

PMID- 18610193
TI  - EVALUATION OF A DYNAMIC METHOD FOR CALIBRATION OF DYE DILUTION CURVES.

PMID- 18610194
TI  - LEFT VENTRICULAR FILLING PRESSURE GRADIENT IN MITRAL INCOMPETENCE.

PMID- 18610195
TI  - PHASES OF DIASTOLE IN VARIOUS SYNDROMES OF MITRAL VALVULAR DISEASE.

PMID- 18610196
TI  - INTRACARDIAC THROMBOSIS AND EMBOLISM IN ENDOMYOCARDIAL FIBROSIS IN UGANDA.

PMID- 18610197
TI  - THE PULMONARY COMPONENT OF THE SECOND HEART SOUND IN FALLOT'S TETRALOGY.

PMID- 18610199
TI  - COMPLETELY HEALED DISSECTION OF THE AORTA WITH DEATH FROM PHLEGMONOUS COLITIS.

PMID- 18610198
TI  - ELECTROCARDIOGRAPHIC STUDIES IN PATIENTS WITH AN ARTIFICIAL PACEMAKER.

PMID- 18610200
TI  - PERFORATION OF THE INTERVENTRICULAR SEPTUM WITH SURVIVAL FOR FIVE YEARS.

PMID- 18610201
TI  - PULMONARY ATRESIA WITH INTACT VENTRICULAR SEPTUM.

PMID- 18610202
TI  - ISOLATED DRAINAGE OF THE INFERIOR VENA CAVA TO THE LEFT ATRIUM.

PMID- 18610203
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610204
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610206
TI  - INTERNATIONAL SOCIETY OF CARDIOLOGY-RESEARCH COMMITTEE MEETING AT MAKARSKA,
      SEPTEMBER, 1963.

PMID- 18610205
TI  - LORD EVANS.

PMID- 18610207
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610208
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610209
TI  - THE FOURTH EUROPEAN CONGRESS OF CARDIOLOGY.

PMID- 18610210
TI  - THE ACCURACY OF THE PHOTOELECTRIC EARPIECE TECHNIQUE IN THE MEASUREMENT OF
      CARDIAC OUTPUT.

PMID- 18610211
TI  - PRESAGING CARDIAC PAIN.

PMID- 18610212
TI  - HAEMODYNAMIC ALTERATIONS INDUCED BY ISOPRENALINE IN PATIENTS WITH OBSTRUCTION TO
      RIGHT VENTRICULAR OUTFLOW.

PMID- 18610213
TI  - ORAL TREATMENT OF A-V BLOCK AND OTHER BRADYCARDIAS WITH SUSTAINED ACTION
      ISOPRENALINE.

PMID- 18610214
TI  - PHENINDIONE JAUNDICE.

PMID- 18610216
TI  - Proceedings of the british cardiac society.

PMID- 18610215
TI  - PROCEEDINGS OF THE BRITISH CARDIAC SOCIETY.

PMID- 18610217
TI  - Cardiovascular research.

PMID- 18610218
TI  - Proceedings of the british cardiac society.

PMID- 18610219
TI  - Pseudo-aplasia of the Right Pulmonary Artery Associated with Right-sided Aortic
      Arch.

PMID- 18610221
TI  - Proceedings of the british cardiac society.

PMID- 18610220
TI  - Jamaican cardiomyopathy.

PMID- 18610222
TI  - Fifth world congress of cardiology.

PMID- 18610223
TI  - Unusual secondary tumour of heart.

PMID- 18610224
TI  - Proceedings of the british cardiac society.

PMID- 18610225
TI  - Proceedings of the british cardiac society.

PMID- 18610226
TI  - Scalar, Vector, and Intracardiac Electrocardiograms in Ebstein's Anomaly.

PMID- 18610228
TI  - Fourth asian-pacific congress of cardiology.

PMID- 18610227
TI  - Elective circulatory arrest with continuous coronary perfusion during
      neurosurgical operations.

PMID- 18610230
TI  - The british heart journal redesigned.

PMID- 18610229
TI  - Fifth European congress of cardiology.

PMID- 18610231
TI  - Mitral atresia and occlusive left atrial thrombus.

PMID- 18610232
TI  - The sixth world congress of cardiology.

PMID- 18610233
TI  - His bundle recordings in right bundle-branch block coexisting with iatrogenic
      right ventricular pre-excitation.
AB  - Iatrogenic right ventricular pre-excitation failed to abolish right bundle-branch
      block in two patients. When ;exclusive' His bundle pacing was performed, the QRS
      complexes, St-V, and St-LVE intervals were similar to the ventricular
      deflections, H-V, and V-LVE (intervals) recorded during sinus rhythm. ;Exclusive'
      pacing of the ordinary muscle at the right ventricular inflow tract produced a
      complete left bundle-branch block pattern without abnormal left axis deviation.
      Pacing of both His bundle and ordinary muscle yielded combination complexes in
      which the right bundle-branch block pattern persisted.The ventricular activation
      process was studied in these beats, as well as during the right and left bundle
      branch block induced by coupled atrial stimulation. It appeared as if certain
      areas of the right septal surface behaved, electrophysiologically, as if they
      belonged to the left ventricle. Impulses emerging from these sites were not
      propagated to the right ventricular free wall. The latter was activated by the
      excitation front emerging through the left bundle system. During right bundle
      branch block the endocardium of the right ventricular inflow was activated before
      the peak of the R in V(1). Bipolar leads, 1 mm apart (with the possible exception
      of the ones over the tricuspid valve), were helpful in mapping the spread of
      activation in the human heart.

PMID- 18610234
TI  - Erratum.
AB  - [This corrects the article on p. 725 in vol. 33.].

PMID- 18610235
TI  - Aberrant atrial conduction.

PMID- 18610237
TI  - Retirement of k. Shirley smith as editor.

PMID- 18610238
TI  - Fifth asian-pacific congress of cardiology.

PMID- 18610239
TI  - Sixth European congress of cardiology.

PMID- 18610240
TI  - Erratum.
AB  - [This corrects the article on p. 230 in vol. 35.].

PMID- 18610241
TI  - Erratum.
AB  - [This corrects the article on p. 288 in vol. 35.].

PMID- 18610242
TI  - Radiographs for publication.

PMID- 18610243
TI  - Safety of coronary arteriography.

PMID- 18610244
TI  - Truncus solitarius pulmonalis.

PMID- 18610245
TI  - Proceedings of the british cardiac society.

PMID- 18610246
TI  - New units for old.

PMID- 18610248
TI  - British Cardiac Society: Abstracts of papers read at 54th Annual General Meeting,
      Manchester, 17 April 1975.

PMID- 18610247
TI  - Lignocaine: effect on coronary blood flow in patients with recent myocardial
      infarction.

PMID- 18610249
TI  - Proceedings of the British Cardiac Society: Private business.

PMID- 18610250
TI  - Progressive systemic sclerosis with complete heart block.
AB  - A case of progressive systemic sclerosis is reported. The patient presented with
      chest pain and an abnormal chest radiograph. Later developments included cardiac
      involvement with complete heart block. The heart block was successfully managed
      with an implanted pacemaker.

PMID- 18610252
TI  - The journal and SI units.

PMID- 18610251
TI  - Symposium on cardiac pathology.

PMID- 18610253
TI  - Proceedings of the british cardiac society.

PMID- 18610255
TI  - Swedish society of cardiology and the british cardiac society.

PMID- 18610254
TI  - Electron microscopical study of myocardial biopsy material in congenital heart
      block.

PMID- 18610256
TI  - A policy for hypertension.

PMID- 18610257
TI  - Myocardial infarction in young men: Study of risk factors in nine countries.

PMID- 18610259
TI  - Erratum.
AB  - [This corrects the article on p. 147 in vol. 38.].

PMID- 18610258
TI  - British cardiac society.

PMID- 18610260
TI  - Imperforate Ebstein's anomaly of the tricuspid valve.

PMID- 18610261
TI  - Rules for diagnosis of arterioventricular discordances and spatial identification
      of ventricles.

PMID- 18610262
TI  - Proceedings of the british cardiac society.

PMID- 18610264
TI  - Proceedings of the british cardiac society.

PMID- 18610263
TI  - The watershed: a factor in coronary vein graft occlusion.

PMID- 18610265
TI  - Surgical treatment of postinfarction left ventricular aneurysm in 32 patients.

PMID- 18610267
TI  - Proceedings of the british cardiac society and Swedish society of cardiology.

PMID- 18610266
TI  - Lignocaine, a new technique for intravenous administration.

PMID- 18610268
TI  - Proceedings of the british cardiac society.

PMID- 18610269
TI  - Modified axial lead system in children.

PMID- 18610271
TI  - Proceedings of the british cardiac society.

PMID- 18610270
TI  - Erratum.
AB  - [This corrects the article on p. 1306 in vol. 40.].

PMID- 18610272
TI  - Proceedings of the british cardiac society.

PMID- 18610273
TI  - Ventricular ectopy.

PMID- 18610274
TI  - Sudden death during marathon racing: hyperpyrexia versus myocardial ischaemia.

PMID- 18610275
TI  - Ischaemic heart disease in young hypertensive women.

PMID- 18610276
TI  - Transient early diastolic murmur and end stage renal disease.

PMID- 18610277
TI  - Treatment of hypertrophic obstructive cardiomyopathy with verapamil.

PMID- 18610278
TI  - The Remler ambulatory blood pressure recording system: Accuracy and reliability.

PMID- 18610279
TI  - Proceedings of the british cardiac society.

PMID- 18610280
TI  - Walter somerville.

PMID- 18610281
TI  - Walter Somerville-notre ami britannique.

PMID- 18610283
TI  - "In Dublin's fair city": Walter Somerville: the early years.

PMID- 18610282
TI  - An appreciation of Walter Somerville.

PMID- 18610284
TI  - Walter Somerville: a tribute.

PMID- 18610285
TI  - Mechanism of influence of PR interval on loudness of first heart sound.

PMID- 18610287
TI  - Proceedings of the british cardiac society.

PMID- 18610286
TI  - Aortic root dissection.

PMID- 18610288
TI  - Proceedings of the british cardiac society.

PMID- 18610290
TI  - Erratum.
AB  - [This corrects the article on p. 285 in vol. 46.].

PMID- 18610289
TI  - Terminology for radiographic projections.

PMID- 18610291
TI  - Atresia of left atrioventricular orifice.

PMID- 18610292
TI  - Proceedings of the british cardiac society.

PMID- 18610294
TI  - Proceedings of the british cardiac society.

PMID- 18610293
TI  - Erratum.
AB  - [This corrects the article on p. 380 in vol. 46.].

PMID- 18610295
TI  - Oxford pacemaker infection trial.

PMID- 18610296
TI  - Echocardiographic diagnosis of isolated pulmonary valve endocarditis.

PMID- 18610297
TI  - Echocardiographic dimensions.

PMID- 18610298
TI  - Uniform requirements for manuscripts submitted to biomedical journals:
      International Committee of Medical Journal Editors.

PMID- 18610300
TI  - Proceedings of the british cardiac society.

PMID- 18610299
TI  - Nomenclature of the ductus arteriosus.

PMID- 18610301
TI  - Erratum.
AB  - [This corrects the article on p. 495 in vol. 49.].

PMID- 18610302
TI  - Proceedings of the british cardiac society.

PMID- 18610303
TI  - Erratum.
AB  - [This corrects the article on p. 112 in vol. 50.].

PMID- 18610305
TI  - Proceedings of the british cardiac society.

PMID- 18610304
TI  - Uniform requirements for manuscripts submitted to biomedical journals:
      International Committee of Medical Journal Editors.

PMID- 18610306
TI  - Proceedings of the british cardiac society.

PMID- 18610307
TI  - Morphological appearance of atherosclerotic lesions of the coronary arteries.

PMID- 18610308
TI  - Coronary artery aneurysms and Kawasaki's disease in an adult.

PMID- 18610309
TI  - Modified Blalock-Taussig operation using polytetrafluoroethylene (Impra) grafts.

PMID- 18610310
TI  - New guidelines for training in adult cardiovascular disease: Guidelines.

PMID- 18610311
TI  - Pathways of preferential atrial conduction.

PMID- 18610312
TI  - Left ventricular platelet deposition after acute myocardial infarction.

PMID- 18610313
TI  - The presentation of symptomatic heart disease in infancy based on 10 years'
      experience (1973-82).

PMID- 18610314
TI  - Cardiac transplantation in the United Kingdom.

PMID- 18610315
TI  - Proceedings of the british cardiac society.

PMID- 18610316
TI  - Lead specificity of the maximum ST/heart rate slope response.

PMID- 18610317
TI  - Pathways of preferential arterial conduction.

PMID- 18610318
TI  - Withering bicentennial celebrations.

PMID- 18610319
TI  - Management of primary pulmonary hypertension.

PMID- 18610320
TI  - Dr Walker reply.

PMID- 18610321
TI  - The authors reply.

PMID- 18610322
TI  - Erratum.
AB  - [This corrects the article on p. 4 in vol. 55, PMID: 3947480.].

PMID- 18610323
TI  - Professor Goodwin reply.

PMID- 18610325
TI  - Dr Dancy reply.

PMID- 18610324
TI  - The authors reply.

PMID- 18610326
TI  - Comparison of electrocardiographic and echocardiographic measures of left
      ventricular hypertrophy in the assessment of aortic stenosis.

PMID- 18610327
TI  - The authors reply.

PMID- 18610329
TI  - Erratum.
AB  - [This corrects the article on p. 33 in vol. 56, PMID: 3730205.].

PMID- 18610328
TI  - Dr Walker reply.

PMID- 18610330
TI  - Radiation hazards for cardiologists.

PMID- 18610331
TI  - The authors reply.

PMID- 18610332
TI  - Reversible renal failure after combined treatment with enalapril and frusemide in
      a patient with congestive heart failure.

PMID- 18610333
TI  - Cardiac club 1922: cardiac society of great britain and ireland 1937.

PMID- 18610334
TI  - The authors reply.

PMID- 18610335
TI  - Radiation in cardiology.

PMID- 18610339
TI  - The authors reply.

PMID- 18610340
TI  - Early results after percutaneous transluminal coronary angioplasty in 400
      patients.

PMID- 18610341
TI  - The authors reply.

PMID- 18610343
TI  - Erratum.
AB  - [This corrects the article on p. 491 in vol. 56.].

PMID- 18610342
TI  - The authors reply.

PMID- 18610344
TI  - Transluminal angioplasty of a stenosis of an internal mammary artery graft.

PMID- 18610345
TI  - Dr Northcote reply.

PMID- 18610347
TI  - Proceedings of the british cardiac society (golden jubilee meeting).

PMID- 18610346
TI  - Dr Somerville reply.

PMID- 18610348
TI  - The authors reply.

PMID- 18610349
TI  - Suppressor T lymphocyte function in patients with idiopathic congestive
      cardiomyopathy.

PMID- 18610351
TI  - Erratum.
AB  - [This corrects the article on p. 441 in vol. 58.].

PMID- 18610350
TI  - The authors reply.

PMID- 18610352
TI  - The authors reply.

PMID- 18610353
TI  - The author reply.

PMID- 18610354
TI  - The author reply.

PMID- 18610355
TI  - The author reply.

PMID- 18610356
TI  - The authors reply.

PMID- 18610357
TI  - The author reply.

PMID- 18610359
TI  - Erratum.
AB  - [This corrects the article on p. 480 in vol. 60.].

PMID- 18610358
TI  - The author reply.

PMID- 18610360
TI  - Relations between members of the British Cardiac Society and industry.

PMID- 18610361
TI  - The authors reply.

PMID- 18610362
TI  - The authors reply.

PMID- 18610363
TI  - Pulmonary capillary haemangiomatosis.

PMID- 18610364
TI  - Erratum.
AB  - [This corrects the article on p. 322 in vol. 61, PMID: 2713188.].

PMID- 18610365
TI  - Erratum.
AB  - [This corrects the article on p. 514 in vol. 61, PMID: 2667594.].

PMID- 18610366
TI  - The authors reply.

PMID- 18610367
TI  - The authors reply.

PMID- 18610368
TI  - The authors reply.

PMID- 18610369
TI  - British Heart Journal: content... and style.

PMID- 18610370
TI  - Views from the past.

PMID- 18610371
TI  - Views from the past.

PMID- 18610373
TI  - Views from the past.

PMID- 18610372
TI  - Views from the past.

PMID- 18610374
TI  - Views from the past.

PMID- 18610376
TI  - Views from the past.

PMID- 18610375
TI  - RITA trial protocol.

PMID- 18610377
TI  - Views from the past.

PMID- 18610378
TI  - Views from the past.

PMID- 18610379
TI  - Proceedings of the british cardiac society.

PMID- 18610380
TI  - Views from the past.

PMID- 18610381
TI  - Erratum.
AB  - [This corrects the article on p. 111 in vol. 64.].

PMID- 18610382
TI  - Non-invasive determination of cardiac output by Doppler echocardiography and
      electrical bioimpedance.

PMID- 18610383
TI  - The authors reply.

PMID- 18610385
TI  - W a jolly.

PMID- 18610384
TI  - Ronald thomson grant 1892-1989.

PMID- 18610386
TI  - Erratum.
AB  - [This corrects the article on p. 174 in vol. 64.].

PMID- 18610387
TI  - Ryanodine.

PMID- 18610388
TI  - Lignocaine.

PMID- 18610390
TI  - Veratrum alkaloids.

PMID- 18610389
TI  - Aspirin.

PMID- 18610391
TI  - Erratum.
AB  - [This corrects the article on p. 116 in vol. 65.].

PMID- 18610392
TI  - Methyl xanthine diuretics.

PMID- 18610393
TI  - Ergometrine (ergonovine).

PMID- 18610394
TI  - Proceedings of the british cardiac society.

PMID- 18610395
TI  - Dicoumarol and warfarin.

PMID- 18610396
TI  - Comment.

PMID- 18610397
TI  - Atropine.

PMID- 18610398
TI  - Reserpine and ajmaline.

PMID- 18610399
TI  - Cardiac glycosides.

PMID- 18610401
TI  - Procaine and procainamide.

PMID- 18610400
TI  - Comment.

PMID- 18610402
TI  - Erratum.
AB  - [This corrects the article on p. 395 in vol. 66.][This corrects the article on p.
      384 in vol. 66.].

PMID- 18610404
TI  - Views from the past.

PMID- 18610403
TI  - Dietary pulmonary hypertension.

PMID- 18610405
TI  - Aconitine and arrhythmias.

PMID- 18610406
TI  - Fagarine.

PMID- 18610407
TI  - Medicinal plant discovery.

PMID- 18610408
TI  - Proceedings of the british cardiac society.

PMID- 18610409
TI  - Erratum.
AB  - [This corrects the article on p. 351 in vol. 67.].

PMID- 18610410
TI  - Proceedings of the british cardiac society.

PMID- 18610411
TI  - Speeding up the review process.

PMID- 18610413
TI  - Neurological comment.

PMID- 18610414
TI  - Limitations of transoesophageal echocardiography in patients with focal cerebral
      ischaemic events.

PMID- 18610416
TI  - From shroud waving to quality of life.

PMID- 18610415
TI  - Comment.

PMID- 18610417
TI  - The further of paediatric cardiology in the United Kingdom.

PMID- 18610419
TI  - Atherosclerosis.

PMID- 18610418
TI  - Erratum.
AB  - [This corrects the article on p. 94 in vol. 69, PMID: 8457406.].

PMID- 18610421
TI  - Comment.

PMID- 18610422
TI  - Strategic planning for cardiac services and the internal market: role of
      catheterisation laboratories in district general hospitals.

PMID- 18610423
TI  - Can any agreement be reached on cholesterol lowering?

PMID- 18610425
TI  - Indexing the British Heart Journal: choice of keywords.

PMID- 18610424
TI  - Erratum.
AB  - [This corrects the article on p. 226 in vol. 70.].

PMID- 18610426
TI  - Cardiovascular pathology in Europe: a new school.

PMID- 18610427
TI  - Erratum.
AB  - [This corrects the article on p. 446 in vol. 71, PMID: 8011408.].

PMID- 18610429
TI  - Erratum.
AB  - [This corrects the article on p. P22 in vol. 71.].

PMID- 18610428
TI  - Echocardiography 1994.

PMID- 18610431
TI  - Simon dack.

PMID- 18610430
TI  - Erratum.
AB  - [This corrects the article on p. P91 in vol. 71.].

PMID- 18610432
TI  - Erratum.
AB  - [This corrects the article on p. 588 in vol. 71.].

PMID- 18610433
TI  - An unusual cause of poor cardiac output.

PMID- 18610434
TI  - Erratum.
AB  - [This corrects the article on p. 536 in vol. 71.].

PMID- 18610435
TI  - Erratum.
AB  - [This corrects the article on p. 105 in vol. 72.].

PMID- 18610440
TI  - The cardiomyopathies.

PMID- 18610436
TI  - Surgical cover for angioplasty.

PMID- 18610441
TI  - Guide wire graffito.

PMID- 18610442
TI  - Echocardiography 1995.

PMID- 18610443
TI  - Erratum.
AB  - [This corrects the article on p. 397 in vol. 73, PMID: 7786645.].

PMID- 18610445
TI  - Pericardial cyst.

PMID- 18610444
TI  - Erratum.
AB  - [This corrects the article on p. 7 in vol. 74, PMID: 7662458.].

PMID- 18610446
TI  - Erratum.
AB  - [This corrects the article on p. 386 in vol. 74, PMID: 7488452.].

PMID- 18610447
TI  - Erratum.
AB  - [This corrects the article on p. 475 in vol. 73, PMID: 7786665.].

PMID- 18610448
TI  - Erratum.
AB  - [This corrects the article on p. 373 in vol. 74, PMID: 7488449.].

PMID- 18610449
TI  - Heart: what we wish to publish.

PMID- 18610450
TI  - Heart: the change of title.

PMID- 18610451
TI  - Cardiac rehabilitation session at BCS meeting.

PMID- 18610452
TI  - Heart and the british heart journal.

PMID- 18610454
TI  - Erratum.
AB  - [This corrects the article on p. 598 in vol. 74.].

PMID- 18610453
TI  - Cardiac museum specimens in London.

PMID- 18610455
TI  - POSTERS: On display in the Exhibition Hall (Hall 4) throughout the meeting.

PMID- 18610456
TI  - Young research workers finalists.

PMID- 18610457
TI  - Echocardiography 1996.

PMID- 18610458
TI  - Non-surgical ablation of the ventricular septum for the treatment of hypertrophic
      cardiomyopathy.

PMID- 18610460
TI  - Erratum.
AB  - [This corrects the article on p. 507 in vol. 76.].

PMID- 18610459
TI  - Echocardiographic diagnosis of a subvalvar aortic membrane.

PMID- 18610461
TI  - Erratum.
AB  - [This corrects the article on p. 490 in vol. 76.].

PMID- 18610462
TI  - Erratum.
AB  - [This corrects the article on p. 1 in vol. 76, PMID: 9071952.].

PMID- 18610463
TI  - Erratum.

PMID- 18610466
TI  - Interventional cardiology.

PMID- 18610465
TI  - Echocardiography 1997.

PMID- 18610467
TI  - Erratum.
AB  - [This corrects the article on p. 485 in vol. 79.].

PMID- 18610468
TI  - BetaBlockade in congestive heart failure.

PMID- 18610469
TI  - Diagnosis of heart failure.

PMID- 18610471
TI  - Present treatment options in congestive heart failure.

PMID- 18610470
TI  - The role of the neurohormonal system in heart failure.

PMID- 18610472
TI  - History of Beta blockers in congestive heart failure.

PMID- 18610473
TI  - Pathophysiology of heart failure.

PMID- 18610474
TI  - Carvedilol tratment of chronic heart failure: a new era.

PMID- 18610475
TI  - BetaAdrenoceptor blockade in congestive heart failure: future perspectives.

PMID- 18610477
TI  - Essential collection.

PMID- 18610476
TI  - Epidemiological burden of heart failure.

PMID- 18610479
TI  - The world wide web takes Heart: www.heartjnl.com.

PMID- 18610480
TI  - Erratum.
AB  - [This corrects the article on p. 548 in vol. 80.].

PMID- 18610481
TI  - Erratum.
AB  - [This corrects the article on p. 171 in vol. 81.].

PMID- 18610482
TI  - Foundations and institutions.

PMID- 18610483
TI  - Hearts and minds.

PMID- 18610484
TI  - Conferences.

PMID- 18610485
TI  - eHEART: www.heartjnl.com.

PMID- 18610486
TI  - Chairmen's summary.

PMID- 18610487
TI  - Interventional cardiology.

PMID- 18610488
TI  - Transplantation.

PMID- 18610489
TI  - Education in heart.

PMID- 18610490
TI  - Professor m j davies, editor heart 1992-99.

PMID- 18610492
TI  - Health campaigns.

PMID- 18610491
TI  - eHEART: www.heartjnl.com.

PMID- 18610494
TI  - Congresses.

PMID- 18610493
TI  - Erratum.
AB  - [This corrects the article on p. 215 in vol. 80.].

PMID- 18610495
TI  - World health organization.

PMID- 18610497
TI  - Institutions.

PMID- 18610496
TI  - Rapid Responses now available on eHeart.

PMID- 18610498
TI  - [Not Available].

PMID- 18610500
TI  - [Not Available].

PMID- 18610501
TI  - Web top 10.

PMID- 18610502
TI  - Web top 10.

PMID- 18610503
TI  - Congresses.

PMID- 18610505
TI  - [Not Available].

PMID- 18610504
TI  - Rapid viewpoints.

PMID- 18610506
TI  - Erratum.
AB  - [This corrects the article on p. 442 in vol. 84.].

PMID- 18610507
TI  - Echocardiography 2000.

PMID- 18610508
TI  - Farm wages and living standards in the Industrial Revolution: England, 1670-1869.

PMID- 18610510
TI  - Allan Award Introduction: Arthur L. Beaudet.

PMID- 18610511
TI  - "Social wonders": fancy, science, and technology in Dickens's periodicals.

PMID- 18610512
TI  - [An analysis of migration patterns in a silk-production center in the late modern
      era: the Yokoyama Inn - in Musashi Province, Tama District, Hachioji - as a case
      study].

PMID- 18610513
TI  - A similarity between viral defense and gene silencing in plants.
AB  - Gene silencing in plants, in which an endogenous gene is suppressed by
      introduction of a related transgene, has been used for crop improvement.
      Observations that viruses are potentially both initiators and targets of gene
      silencing suggested that this phenomenon may be related to natural defense
      against viruses. Supporting this idea, it was found that nepovirus infection of
      nontransgenic plants induces a resistance mechanism that is similar to transgene
      induced gene silencing.

PMID- 18610514
TI  - Falling behind: Americans' access to medical care deteriorates, 2003-2007.
AB  - The number and proportion of Americans reporting going without or delaying needed
      medical care increased sharply between 2003 and 2007, according to findings from
      the Center for Studying Health System Change's (HSC) nationally representative
      2007 Health Tracking Household Survey. One in five Americans--59 million people-
      reported not getting or delaying needed medical care in 2007, up from one in
      seven--36 million people--in 2003. While access deteriorated for both insured and
      uninsured people, insured people experienced a larger relative increase in access
      problems compared with uninsured people. Moreover, access declined more for
      people in fair or poor health than for healthier people. In addition, unmet
      medical needs increased for low-income children, reversing earlier trends and
      widening the access gap with higher-income children. People reporting access
      problems increasingly cited cost as an obstacle to needed care, along with rising
      rates of health plan and health system barriers.

PMID- 18610515
TI  - Alan Staff.

PMID- 18610516
TI  - Symmetry perception in an insect.
AB  - Symmetrical visual patterns have a salient status in human perception, as evinced
      by their prevalent occurrence in art, and also in animal perception, where they
      may be an indicator of phenotypic and genotypic quality. Symmetry perception has
      been demonstrated in humans, birds, dolphins and apes. Here we show that bees
      trained to discriminate bilaterally symmetrical from non-symmetrical patterns
      learn the task and transfer it appropriately to novel stimuli, thus demonstrating
      a capacity to detect and generalize symmetry or asymmetry. We conclude that bees,
      and possibly flower-visiting insects in general, can acquire a generalized
      preference towards symmetrical or, alternatively, asymmetrical patterns depending
      on experience, and that symmetry detection is preformed or can be learned as
      perceptual category by insects, because it can be extracted as an independent
      visual pattern feature. Bees show a predisposition for learning and generalized
      symmetry because, if trained to it, they choose it more frequently, come closer
      to and hover longer in front of the novel symmetrical stimuli than the bees
      trained for asymmetry do for the novel asymmetrical stimuli. Thus, even organisms
      with comparatively small nervous systems can generalize about symmetry, and
      favour symmetrical over asymmetrical patterns.

PMID- 18610517
TI  - [Some useful points].

PMID- 18610518
TI  - [DRG: please, no lottery with numbers].

PMID- 18610519
TI  - [Decubitus ulcer in children--an often underrated nursing problem].

PMID- 18610520
TI  - [Finding the "iceberg" at ground level].

PMID- 18610521
TI  - [Support during a complicated start in life].

PMID- 18610522
TI  - ["Connection and trust are important"].

PMID- 18610523
TI  - [Progressive adjournment--what next?].

PMID- 18610524
TI  - [Continuous building with great obstacles].

PMID- 18610525
TI  - ["Patients are more than cases"].

PMID- 18610526
TI  - [Small project, great reaction].

PMID- 18610527
TI  - [Polyvalent, omnipresent, efficacious].

PMID- 18610528
TI  - [Observance during compressive treatment].

PMID- 18610529
TI  - [Choosing a method of dialysis: no drama but information].

PMID- 18610530
TI  - [Alcohol and sports: a bad mixture].

PMID- 18610531
TI  - [Oxytocin is favored during birth, then not useful].

PMID- 18610532
TI  - [Even the children get sick].

PMID- 18610533
TI  - Precaecal and postileal metabolism of P, Ca and N in pigs as affected by
      different carbohydrate sources fed at low level of P intake.
AB  - Three different carbohydrate sources (cellulose on wood basis, maize starch and
      apple pectin) in combination with a low phosphorus (P) basal diet were fed to
      eight pigs fitted with single ileum-T-cannulas in a balance trial. The effects on
      net disappearance of dry matter, N, P and Ca as well as phytate (IP6) degradation
      in the intestine were studied. A basal diet and three diets supplemented with 25%
      of one carbohydrate source were applied in three experimental periods following
      an incomplete Latin Square design. Animals were housed individually in balance
      crates. After 15 days of adaptation to the diets, five days of total excreta
      collection were followed by two days of spot sampling of ileal digesta. The
      results showed a significantly decreasing effect of cellulose on the precaecal,
      postileal and total tract digestibility of DM, N and P. Starch reduced precaecal
      IP6 degradation and P digestibility. The addition of pectin negatively affected
      the precaecal digestibility of DM, N and Ca as well as the total tract
      digestibility of P and Ca. Postileally, cellulose and pectin caused a net
      secretion while starch induced a net absorption of P.

PMID- 18610534
TI  - Lysine maintenance requirement and efficiency of its utilisation in young pigs as
      estimated by comparative slaughter technique.
AB  - An experiment was carried out on weaner pigs (initial BW 10.8 kg) to estimate the
      maintenance requirement for lysine (Lys) and its marginal efficiency of
      utilisation using a comparative slaughter technique. Three groups of six pigs
      each were fed purified diets for 21 days supplying Lys at 19.5, 78 or 195 mg/kg
      W0.75, which corresponded to 50, 200 or 500% of the assumed maintenance
      requirement. All other essential amino acids were given at 50% excess. At the end
      of the experiment, pigs were killed for whole-body nitrogen (N) and amino acid
      analysis. A representative group of six pigs was analysed at the beginning of the
      experiment. Based on regression equations, relating Lys or N retention to Lys
      intake, Lys requirement for zero Lys retention was estimated to be 121 mg/kg
      W0.75, while Lys requirement corresponding to zero N retention was 41.7 mg/kg
      W0.75. At N equilibrium, the pigs lost 65 mg of Lys per kg W0.75 daily while at
      zero Lys retention, the daily N retention was 156 mg/kg W0.75 . The marginal
      efficiency of lysine utilisation was 0.91. It is concluded that zero lysine
      retention is a better criterion of lysine maintenance requirement than zero N
      retention.

PMID- 18610535
TI  - Methionine, folic acid and vitamin B12 in growing-finishing pigs: impact on
      growth performance and meat quality.
AB  - Growth performance, metabolic variables, and meat quality were measured in 78
      growing-finishing pigs using supplements of 0 (C), or 0.2% of DL-methionine (M),
      and three combinations of folic acid [mg/kg] and cyanocobalamin [microg/kg],
      respectively 0 and 0 (V0), 10 and 25 (V1), and 10 and 150 (V2) in a 2 x 3
      factorial arrangement. Feed conversion was lower (p = 0.05) in M than in C pigs
      during the growing period (0-4 weeks). Both V1 and V2 treatments increased plasma
      vitamin B12 (p < 0.01) and decreased plasma homocysteine (p < 0.01). Plasma 5
      methyl-tetrahydrofolates were the lowest, highest and intermediate in V0, V1 and
      V2 pigs (p < 0.04), respectively. In V2 meat, folates were 32% higher, vitamin
      B12, 55% higher and homocysteine, 28% lower than in V0 (p < 0.01). Oxidative
      stability of the fresh meat was similar among treatments during a storage period
      of 42 days. Therefore, methionine supplements improved growth performance during
      the growing period. Vitamin supplements interacted with the methionine cycle
      pathway, increased vitamin content of pork meat but did not improve oxidative
      stability of the fresh meat during storage.

PMID- 18610536
TI  - The influence of an increased cobalt supply on ruminal parameters and microbial
      vitamin B12 synthesis in the rumen of dairy cows.
AB  - The aim of the study was to examine the effects of an elevated dietary cobalt
      supply to dairy cows on rumen fermentation parameters and microbial vitamin B12
      synthesis in the rumen. Five lactating dairy cows fitted with a ruminal and a
      duodenal cannula were subsequently fed either a ration containing only the native
      cobalt content (0.17 mg Co/ kg DM) or a ration supplemented with cobalt sulphate
      (0.29 mg Co/kg DM). The pH-value, the ammonia concentration as well as the
      concentration and the molar proportions of short chain fatty acids in the rumen
      were not significantly influenced by feeding the ration with the higher cobalt
      content. While there was no difference in microbial protein flow, the cobalamin
      flow at the duodenum was significantly elevated in supplemented animals (3.67 +/-
      0.69 vs. 8.63 +/- 2.22 mg B12/d). The efficiency of cobalt utilisation for
      ruminal vitamin B12 synthesis was calculated to be 7.1 +/- 1.3% for the
      unsupplemented and 9.5 +/- 2.4% for the supplemented ration. Further
      investigation has to prove if there are any benefits for cows resulting from the
      elevated cobalamin synthesis measured, caused by feeding higher amounts of
      dietary cobalt.

PMID- 18610537
TI  - Responses of whole body protein synthesis and degradation to plantain herb in
      sheep exposed to heat.
AB  - An experiment including a [1-(13)C]leucine isotope dilution and a nitrogen
      balance were carried out to determine the effect of feeding plantain herb
      (Plantago lanceolata L.) on whole body protein synthesis (WBPS) and degradation
      in sheep kept at thermoneutral temperature (20 degrees C) or exposed to heat (30
      degrees C). The animals were fed either mixed hay of orchardgrass and reed
      canarygrass (Hay-diet) or Hay-diet and plantain (9:1) (PL-diet) at maintenance
      level using a crossover design. Nitrogen intake was higher (p < 0.0001) for the
      Hay-diet than for the PL-diet, but N balance remained similar between diets and
      was higher (p = 0.003) during heat exposure than at thermoneutral temperature.
      The WBPS was numerically lower (p = 0.10) for the PL-diet than for the Hay-diet.
      The direction of the response to heat exposure differed (p = 0.04) between diets:
      after feeding the PL-diet the WBPS increased from 15.2-16.9 g x kgW(-0.75) x d(
      1), whereas it decreased after feeding the Hay-diet from 17.5-16.6 g x kgW(-0.75)
      x d(-1). The present results suggest that the PL-diet may have a positive impact
      for WBPS during heat exposure, and could be used for rearing sheep as an
      alternative to the Hay-diet.

PMID- 18610538
TI  - Evaluation of the effects of dietary particle fractions on fermentation profile
      and concentration of microbiota in the rumen of dairy cows fed grass silage-based
      diets.
AB  - The study evaluated the effects of three different theoretical particle lengths
      (TPL) of grass silage on the distribution of particle fractions of the diet and
      the resulting effects on fermentation profile and concentrations of protozoa and
      mixed bacterial mass in the rumen of three lactating Holstein cows fed total
      mixed rations (45% grass silage, 5% grass hay and 50% concentrate) ad libitum.
      Decreasing TPL of grass silage (long, medium, short) reduced particles retained
      on the 19-mm sieve of the Penn State Particle Separator, while particle fractions
      from 8 mm to 19 mm and smaller than 8 mm were increased. Different TPL did not
      affect pH and the concentration of volatile fatty acids in the rumen. However,
      lowering the TPL from long to medium increased significantly the bicarbonate
      concentration, acetate proportion and protozoal number in the rumen, whereas the
      proportion of bacterial protein in ruminal digesta and its amino acid
      concentration were significantly increased by the short TPL. For the current
      feeding conditions, it can be concluded that increasing the fraction of particles
      between 8 and 19 mm and probably even the fraction below 8 mm by decreasing TPL
      of grass silage do not adversely affect rumen conditions and can be beneficial in
      terms of optimising concentration and activity of ruminal microbiota in high
      yielding dairy cows.

PMID- 18610539
TI  - On the effects of the concentrate proportion of dairy cow rations in the presence
      and absence of a fusarium toxin-contaminated triticale on cow performance.
AB  - The aim of the present study was to investigate the effects of a deoxynivalenol
      (DON) contaminated ration with a concentrate proportion of 50%, on the
      performance of dairy cows (Period 1), and to examine the effects when the
      concentrate proportion was elevated to 60% compared to a ration with 30%
      concentrates (Period 2). In Period 1, 13 lactating German Holstein cows (Myco
      group, on average 29 days in milk) were fed the experimental diet (on average 5.3
      mg DON/kg DM) as total mixed ration over 11 weeks, while another 14 cows (on
      average 33 days in milk) received a control diet. Both rations contained 50%
      concentrates (on DM basis). In Period 2 (18 weeks), the same 27 cows plus five
      additional cows were divided into four groups: Control-30 (30% concentrates),
      Myco-30 (30% concentrates, 4.4 mg DON/kg DM), Control-60 (60% concentrates), Myco
      60 (60% concentrates, 4.6 mg DON/kg DM). The overall performance level was
      characterised by a mean daily DM intake of 17.9 kg and a mean daily milk
      production of 26.7 kg fat corrected milk (FCM) in Period 1 and 17.3 kg DM intake
      and 24.5 kg FCM in Period 2, respectively. In both periods cows fed the Fusarium
      toxin-contaminated diets consumed more DM (in Period 2 only significant for group
      Myco-30) resulting from stimulating effects on the ingesta passage rate of the
      natural contaminated Fusarium-infected triticale. In Period 1, cows fed the
      Fusarium toxin-contaminated diet had a significantly higher milk yield, milk urea
      and somatic cell count, whereas milk fat and protein concentration and fat-to
      protein-ratio (FPR) were significantly lower. In Period 2, on a low concentrate
      level, FCM was significantly higher in group Myco-30. On a high concentrate
      level, group Myco-60 produced significantly more milk, but milk fat and protein
      concentration, FPR and milk urea were significantly lower. A concentrate
      proportion of 60% had a depressing effect on milk fat concentration but was
      significantly more pronounced in the presence of Fusarium toxin-contaminated and
      Fusarium damaged-triticale.

PMID- 18610540
TI  - A survey of green burial sites in England and Wales and an assessment of the
      feasibility of a groundwater vulnerability tool.
AB  - Since 1994, 200 'green' or natural burial sites have been developed in the UK and
      Eire, attracting regulatory attention because of perceived risks to groundwater.
      Here, a survey of natural burial practice in England and Wales (n=49 of 141
      elicited) is presented, providing data on operational trends and supporting the
      design of a groundwater vulnerability assessment tool. Natural burial grounds are
      generally small in area (< 0.8 ha), adopt a mean single burial depth of 1.45 m
      bgl and a mean plot density of ca. 1480 graves ha(-1). A vulnerability screening
      tool is described that allows a desk-based evaluation of sites by reference to
      seven groundwater risk attributes. Initial feasibility is evaluated through
      application to 131 sites.

PMID- 18610541
TI  - A novel electrospun polysulfone fiber membrane: application to advanced treatment
      of secondary bio-treatment sewage.
AB  - Electrospun nanofibers and fine fibers have been used to remove submicron
      particles in air filtration. In this paper, direct-and polyaluminium chloride
      (PAC) pre-coagulation filtration of secondary bio-treatment sewage was studied
      using electrospun polysulfone fiber membrane (EPSFM). According to the results
      obtained, for direct filtration, suspended solids (SS), chemical oxygen demand
      (COD(Cr)) and NH3-N decreased 86.7, 71.2, 91.7% respectively, in filtrate of
      secondary bio-treatment sewage, while for PAC pre-coagulation filtration, the
      removal rate of SS, COD(Cr) and NH3-N reached 91.3, 85.3, 93.3 % respectively.
      EPSFM had a high efficiency in removing NH3-N, COD(Cr) and SS, especially for
      micron and submicron particles. EPSFM can reduce the content of some toxic
      metals, such as Cu, Zn and Ti, through interception and adsorption mechanism and
      can also remove dissolved organic matter such as humics and proteins through
      interception mechanism. EPSFM can remove some of volatile organic chemicals
      (VOCs) by adsorption and filtration, the removal rate of VOCs was in the range of
      59-100 %. The number of VOCs in secondary bio-treatment sewage and its filtrate
      from direct filtration were 27 and 18 respectively, the major VOCs were benzene-,
      cyclohexane-, adamantine- and hydrocarbon derivates.

PMID- 18610542
TI  - Natural attenuation of oil spills in Patagonian soils. Characterization by 1H NMR
      spectroscopy.
AB  - The natural attenuation of oil spill contaminated soils, with different exposure
      times, in Patagonian environment was evaluated by the use of several parameters
      to quantify the degree of changes in the composition. Column (CC) and gas
      chromatography (GC); UV-visible and 1H NMR techniques were used to determine
      compositional and structural indexes. The results show that the nC18/Phytane GC
      index, that was 1.5 for crude oil, decreased with exposure time to values between
      0.97-0.17 in the residues. The percentages for the four aliphatic (H1-H4) and the
      aromatic (H(A)), proton types, determined by 1H NMR, were: 12.9-34.4 (H1), 43.3
      60.2 (H2), 4.24-24.2 (H), 1.33-17.9 (H4), and 0.44-4.81 (HA), in crude oil and
      residues, respectively. Furthermore, the characterization of significant 1H NMR
      signals indicated the presence of carboxylic acid hydrogens in the polar fraction
      of the crude oil and of residues of two years age. The Principal Components
      Analysis (PCA) of the parameters determined by CC, GC and NMR showed that the
      first three principal components (1st, 2nd, and 3 rd PC), accounted for more than
      84% of variance. The 1st PC is largely influenced by H, H,, H, H, and the
      nC,,/Phytane GC parameter, in the order given. The evaluation of the different
      parameters by PCA suggests that 1H NMR is more useful than GC to evaluate the
      degree of the chemical transformations of oil spills in soils

PMID- 18610543
TI  - Detection and prevention of enhanced biological phosphorus removal deterioration
      caused by Zoogloea overabundance.
AB  - A sequencing batch reactor was operated in the conventional anaerobic-aerobic
      mode for enhanced biological phosphorus removal using acetate as the sole
      substrate. Despite the nutrients concentrations in the influent being high enough
      to satisfy the biological requirements, Zoogloea ramigera managed to grow in the
      system until it had negative effects on the process performance. The excess of
      exocellular polymeric material produced by this microorganism contributed to a
      viscous bulking phenomenon and caused important settling problems. The
      examination of the sludge under the microscope was a valuable tool to diagnose
      the cause of the imbalance in the process. The strategy adopted to avoid the
      deterioration of the process (changing key operational factors affecting the Z.
      ramigera development) allowed the successful recovery the enhanced biological
      phosphorus removal system. The effectiveness of this approach was confirmed by
      analyzing several parameters along the operational period (SVI, Y(PO4), TSS,
      %VSS...) together with microbiological examinations of the sludge.

PMID- 18610544
TI  - Fate of polycyclic aromatic hydrocarbons during composting of oily sludge.
AB  - In order to assess the effectiveness of aerobic degradation with emphasis on the
      16 U.S. EPA priority polycyclic aromatic hydrocarbons (PAH), oily sludge
      generated by a dissolved air flotation flocculation unit of a wastewater
      treatment plant in a petroleum refinery was amended with remediated oil
      contaminated soil and non-mature garden waste compost 40:40:20 (wet weight)
      respectively. About 21 t of the mixture with a top-layer formed by 30 cm of
      remediated soil was treated in a 28 m3 air-forced reactor. The PAH concentration
      was monitored for 370 days. In the top-layer, a reduction of 88 % of the total
      extractable PAH was measured at day 62 and a final reduction of 93% at day 370.
      In the mixture, a reduction of 72% in total PAH was measured at day 62, followed
      by fluctuation in concentration with a final measured reduction of 53% at day
      370. The analysis of individual PAH in the mixture suggested that volatilization
      and biodegradation are the main mechanisms responsible for the reduction of 2
      ring PAH and 3-4 ring PAH, respectively. Fluctuation of 5-6 ring PAH
      concentrations with increase observed at the end of the period might result from
      a combination of the following: (i) sequestration of large PAH in the organic
      matrix (reducing bioavailability, biodegradability and eventually,
      extractability) and desorption as composting progresses; (ii) heterogeneous
      distribution of the stable large PAH in the mixture, thus affecting sampling. It
      was concluded that one-time composting in static-aerated biopiles with organic
      amendments as the sole strategy to treat oily sludge is very effective in
      reducing the content of 2-4 ring PAH, but it is not effective in reducing the
      content of 5-6 ring PAHs, even after a relatively long time span (370 d). The
      concentrations measured in the remediated soil that formed the top layer after 62
      days of composting suggests that further relevant reduction of residual PAH (89%
      of total PAH and 69% of 5-6 ring PAH) can be obtained if the contaminated masses
      are exposed to a second thermophilic phase. This could be achieved by adding new
      easily biodegradable organic amendments to the contaminated masses after some
      months of composting, remixing and composting again for a minimum additional
      period of 2 months.

PMID- 18610545
TI  - Nitrogen loss during solar drying of biosolids.
AB  - Solar drying has been used extensively to dewater biosolids for ease of
      transportation and to a lesser degree to reduce pathogens prior to land
      application. The nitrogen in biosolids makes them a relatively inexpensive but
      valuable source of fertilizer. In this study, nitrogen loss from tilled and
      untilled biosolids was investigated during the solar drying process. Samples of
      aerobically and anaerobically digested biosolids during three solar drying
      experiments were analyzed for their nitrate (NO3-) and ammonium (NH4+) ions
      concentrations. Nitrogen losses varied depending on the solar drying season and
      tillage. Although not directly measured, the majority of nitrogen loss occurred
      through ammonia volatilization; organic nitrogen content (organic N) remained
      relatively stable for each sample, nitrate concentrations for the majority of
      samples remained below detectable levels and the decline of ammonium-nitrogen
      (NH4(+)-N) generally followed the trend of moisture loss in the biosolids.

PMID- 18610546
TI  - Uptake of phosphorus by filamentous bacteria and the role of cation on
      polyphosphates composition.
AB  - Many microorganisms have the ability to store phosphorus as polyphosphates in
      volutin granules. The aim of the research was to characterise the phosphorus
      sequestered by filamentous microorganisms present in the foam. Also the
      importance of required cations like potassium and magnesium in the process of
      phosphorus uptake by filamentous microorganisms was examined. Electron microscopy
      and energy dispersive X - ray analysis were used to define the composition of
      polyphosphate granules in filamentous bacteria.

PMID- 18610547
TI  - Interactions between phosphorus feeding strategies for pigs and dairy cows and
      separation efficiency of slurry.
AB  - Phosphorus (P) in manure is a nutrient source for plants, but surplus P amended
      to fields represents a risk to the environment. This study examines the
      interactions between low-P diets for pigs and dairy cows and the separation of
      animal slurry into a solid P fraction and a liquid fraction. Replacing inorganic
      phosphates with phytase in pig feed reduced the concentration of P in slurry by
      35%, but supplementing concentrates to dairy cows did not affect the P
      concentration in cattle slurry. Particle-size fractions of the slurry were not
      affected by these dietary changes. The amount of dry matter (DM) in the < 0.025
      mm fraction was greater in pig slurry than in cattle slurry, but the relative
      amounts of P and nitrogen (N) were larger in the > 0.025 mm fraction. Replacing
      feed phosphate, in the form of mono-calcium phosphate, with phytase in the pig
      diet reduced the separation index (efficiency) of P from 80% to 60%.

PMID- 18610548
TI  - The effect of different nitrogen sources on denitrification with PHB under
      aerobic condition.
AB  - This study investigated the effectiveness of denitrification under aerobic
      conditions depending on nitrogen forms in synthetic wastewater (ammonium, or
      ammonium and nitrite). Activated sludge was cultivated in a sequencing batch
      reactor with municipal wastewater enriched by acetate. Poly-beta-hydroxybutyrate
      (PHB) was accumulated in activated sludge to 0.35 g PHB g(-1) VSS. Activated
      sludge, cultivated in such conditions, was used in further experimental series.
      The duration of each series was 24 h. Two types of synthetic wastewater, with
      acetate as the carbon source, were used in this study. One type of wastewater
      contained only ammonium; the second one was enriched also by nitrite. The amount
      of nitrogen reduced by the microorganisms in the activated sludge was 22.5 mg
      N(red) l(-1) when ammonium was the only nitrogen source in wastewater, and a 3
      fold increase was observed in the presence of two nitrogen sources: ammonium and
      nitrite. Simultaneous consumption of organic substances in wastewater (external
      source of electron donors) and intracellularly stored poly-beta-hydroxybutyrate
      in activated sludge (endogenous carbon source) was revealed. COD consumption to
      reduce 1 mg N-oxides, in series with wastewater containing ammonium, was 8.4 mg
      COD. However, in series using wastewater with ammonium and nitrite, a 3-fold
      decrease in COD/N(red) ratio was observed.

PMID- 18610549
TI  - Effects of nitrate on the UV photolysis of H2O2 for VOCs degradation in an
      aqueous solution.
AB  - The major objective of this study was to delineate the effect of nitrate on the
      UV oxidation of benzene and toluene, dissolved in less than 100 microg l(-1), by
      conducting a bench-scale operation at various reaction times and with various
      initial concentrations of H2O2 and NO3-. The oxidation of benzene and toluene can
      be expected to be only about 10% and 18%, respectively, through the photolysis of
      H2O2 (initial conc. of 50 mg l(-1)), where the reactor was operated at a reaction
      time of 2 min, with an initial NO(3-)-N concentration of 5 mg l(-1). Nitrate
      clearly hindered UV oxidation when the initial H2O2 concentration in the reactor
      was less than 50 mg l(-1). Even if approximately 40% removal could be achieved
      under the conditions mentioned above (an initial H2O2 concentration of 200 mg l(
      1) at a reaction time of 9 min, with a high UV dose), the operating conditions
      for the 40% removal might be beyond the practical limits applied for effluents
      discharged from wastewater treatment plants. The results of the experiment also
      indicate that benzene and toluene can be oxidized in very limited amounts through
      direct photolysis, without additional oxidation by hydroxyl radicals.

PMID- 18610550
TI  - Dissolved air flotation (DAF) for primary and tertiary treatment of municipal
      wastewaters.
AB  - Tertiary treatment of municipal wastewater by dissolved air flotation was studied
      on a pilot-scale. The effects of coagulant dose, flocculation pattern, dispersion
      water recycle ratio and hydraulic surface load on process performance were
      evaluated. The treatment of primary effluents by dissolved air flotation was
      investigated to assess the suitability of this process for the treatment of
      heavily polluted effluents and wastewater treatment plant by-passes. The tertiary
      dissolved air flotation process typically achieved 90-99% reductions in the
      numbers of enteric microbes (total coliforms, enterococci and F-RNA coliphages).
      The average reductions of total phosphorus and chemical oxygen demand were 55-81%
      and 28-39%, respectively. Increasing the polyaluminium chloride coagulant dose
      from 2 to 10 mgAl(3+) l(-1) and the dispersion water recycle ratio from 11 to 22%
      improved the efficiency of the process. Changes in the flocculation conditions
      (range of G-values 10-55 s(-1); retention time 4-8 min) and hydraulic surface
      load (5 or 10 m h(-1)) did not clearly affect the process efficiency. The
      dissolved air flotation process decreased the numbers of enteric microbes and
      reduced total phosphorus, chemical oxygen demand and suspended solids from the
      primary treated wastewaters on average by 98-99.8%, 90%, 47% and 77%,
      respectively. The dissolved air flotation process was demonstrated to be a
      suitable method for efficient tertiary treatment of wastewaters, as well as for
      the elimination of peak pollution loads or by-pass wastewaters during the
      treatment plant overloading situations.

PMID- 18610551
TI  - Alternative materials for adsorption of heavy metals and petroleum hydrocarbons
      from contaminated leachates.
AB  - In the present work, waste products from forest industries (sawdust, pine bark
      and fibre sludge ash), as well as some biological materials (peat, shrimp shells
      and seaweed), have been investigated with respect to their capacities to adsorb
      metals and hydrocarbons from contaminated waters. Batch and column experiments
      were carried out with artificial metal ion solutions and contaminated leachates
      from an industrial landfill. The fibre sludge ash and the Sphagnum peat showed
      the highest sorption capacities for metals among the materials studied in batch
      experiments with single-metal solutions. The uptake of metals by the fibre ash
      for the metals studied was: Cu and Pb 112 microg g(-1), Zn 115 microg g(-1) and
      Cr 97 microg g(-1). For peat the uptake was: Pb 109 microg g(-1), Cu 105 microg
      g(-1), Zn 100 microg g(-1) and Cr 99 microg g(-1). These materials were also
      effective in adsorption of diesel oil, and the n-alkanes C16 and C12. Peat and
      ash adsorbed respectively 36.6 and 36.4 mg g(-1) of C12, 1.84 and 1.94 mg g(-1)
      of C16 and for both 0.98 mg g(-1) of diesel oil. Bark adsorbed diesel oil to 0.83
      mg g(-1). In the column experiments, the removal of metals from a contaminated
      landfill leachate by ash and peat was lower than from artificial solutions with
      only a few metals. The results suggest interference from other components in the
      leachates, such as competition of ions for the same active sites. It is quite
      clear that laboratory tests can overestimate the performance of adsorbents and
      that experiments should be specific for the intended application. For most of the
      metals studied in columns, peat appeared to be the best adsorbent, with respect
      to both sorption capacity and service time. The addition of 10% by weight of
      fibre ash to the peat gave higher adsorption capacities for Cd, Ni and Pb but
      lower for the Cu and Zn.

PMID- 18610552
TI  - Herpes simplex virus helicase-primase inhibitors: recent findings from the study
      of drug resistance mutations.
AB  - After several decades during which nucleoside analogues (especially acyclovir and
      penciclovir and their prodrugs) have benefited many patients suffering from
      herpes simplex virus (HSV) infections, the discovery of the helicase-primase
      inhibitors (HPIs) represents an interesting new approach. Although antiviral
      resistance has not been a major problem for nucleoside analogues in
      immunocompetent patients, the problem of acyclovir resistance in
      immunocompromised patients is well documented. Several HPIs are extremely potent
      antiviral compounds and may, therefore, offer an important alternative therapy in
      these patients. The potential for synergy, not just for the inhibition of virus
      replication but also to delay the appearance of drug-resistant virus, needs to be
      thoroughly investigated. The study of resistance to HPIs has been important
      towards understanding the mechanism of action of these compounds and confirming
      the target function. However, during the course of our studies on HPI resistance,
      we have made a number of interesting observations that may be relevant to their
      clinical use. This article draws attention to the major observations on HPI
      resistance reported by others and to our own recently published observations that
      have extended this expanding area of antiviral research.

PMID- 18610553
TI  - Anti-influenza virus activity of propolis in vitro and its efficacy against
      influenza infection in mice.
AB  - BACKGROUND: Propolis has been used worldwide as a dietary supplement to maintain
      and improve human health. We examined whether ethanol extracts of Brazilian
      propolis exhibit antiviral activity against influenza virus in vitro and in vivo.
      METHODS: Among 13 ethanol extracts screened in a plaque reduction assay, four
      showed anti-influenza virus activity. The anti-influenza efficacy of the four
      extracts was further examined in a murine influenza virus infection model. The
      mice were infected intranasally with influenza virus, and the four extracts were
      orally administered at 10 mg/kg three times daily for seven successive days after
      infection. RESULTS: In this infection model, only one extract, AF-08, was
      significantly effective at 10 mg/kg in reducing the body weight loss of infected
      mice. The doses of 2 and 10 mg/kg were also effective in prolonging the survival
      times of infected mice significantly, but 0.4 mg/kg was not. The anti-influenza
      efficacy of AF-08 at 10 mg/kg was confirmed in a dose-dependent manner in mice.
      AF-08 at 10 mg/kg significantly reduced virus yields in the bronchoalveolar
      lavage fluids of lungs in infected mice as compared with the control. The
      reduction of virus yields by AF-08 at 10 mg/kg significantly corresponded to
      those induced by oseltamivir at 1 mg/kg twice daily from day 1 to day 4 after
      infection. CONCLUSION: The Brazilian propolis AF-08 was indicated to possess anti
      influenza virus activity and to ameliorate influenza symptoms in mice. AF-08 may
      be a possible candidate for an anti-influenza dietary supplement for humans.

PMID- 18610554
TI  - Antiviral activities and phosphorylation of 5-halo-2'-deoxyuridines and N
      methanocarbathymidine in cells infected with vaccinia virus.
AB  - BACKGROUND: The antipoxviral activities and phosphorylation of N
      methanocarbathymidine ([N]-MCT) and four 5-halo-2'-deoxyuridines, namely 5-fluoro
      (FdU), 5-chloro-(CldU), 5-bromo-(BrdU), and 5-iodo-(IdU) derivatives, were
      explored. METHODS: Antiviral activities and nucleoside metabolism were determined
      in C127I mouse, LLC-MK2 monkey, and A549 human cells infected with thymidine
      kinase-containing and -deficient (TK+ and TK-) vaccinia (WR strain) viruses.
      RESULTS: The antiviral potencies of CldU, BrdU and IdU were increased 16-26-fold
      in LLC-MK2 cells infected with TK+ compared with TK- virus infections, but
      enhancement of activity was much less in the other cell lines. (N)-MCT was nearly
      equally active against TK+ and TK- viruses in the three cell lines. Antiviral
      activity of FdU was associated with cytotoxicity. Uninfected and infected cells
      metabolized compounds to mono-, di- and triphosphates. The thymidine, BrdU and
      IdU triphosphate levels were higher in C127I and LLC-MK2 cells infected with TK+
      than with TK- virus. (N)-MCT monophosphate levels were much higher in TK+ virus
      infected cells, but without corresponding increases in (N)-MCT triphosphate.
      Furthermore, TK+ virus infections did not appreciably alter (N)-MCT triphosphate
      levels in other mouse (L929), monkey (MA-104 and Vero) and human cell lines
      (A549). Antiviral potency of the compounds was greater in C127I than in LLC-MK2
      cells, yet lower intracellular triphosphate levels were found in C127I cells.
      CONCLUSION: We conclude that viral TK plays an important role in increasing the
      antiviral potencies of these compounds in some cell lines, but minimally in
      others. These findings may have implications in treating infected animals with
      compounds that are dependent upon poxvirus TK for their activation, because viral
      TK activity may vary greatly due to cell type.

PMID- 18610555
TI  - Combinations of 2'-C-methylcytidine analogues with interferon-alpha2b and triple
      combination with ribavirin in the hepatitis C virus replicon system.
AB  - BACKGROUND: Hepatitis C virus (HCV) polymerase is an essential enzyme for HCV
      replication and has multiple inhibitor binding sites making it a major target for
      antiviral intervention. It is apparent that no single drug can inhibit HCV
      replication in humans. Hence, combinations of nucleoside analogues beta-D-2'-C
      methylcytidine (2'-C-MeC; NM-107) or beta-D-2'-deoxy-2'-fluoro-2'-C
      methyleytidine (2'-F-C-MeC; PSI-6130) with interferon-alpha2b (IFN-alpha2b) or
      triple combination with ribavirin (RBV) were evaluated. METHODS: Huh-7 cells
      containing the self-replicating subgenomic HCV replicon (Clone B) were used for
      drug combination studies. After drug treatment for 5 days, total cellular RNA was
      then extracted and both ribosomal RNA and HCV replicon RNA were amplified in a
      single-step multiplex real-time PCR assay. Drug interaction analyses were
      performed using the CalcuSyn program. RESULTS: Double combinations of 2'-C-MeC or
      2'-F-C-MeC with IFN-alpha2b at all ratios tested had weighted average combination
      index (Cl(wt)) values <1 indicating synergistic inhibition of HCV replication in
      the replicon system. For the triple combinations of IFN-alpha2b plus RBV with
      either 2'-C-MeC or 2'-F-C-MeC, the Cl(wt) values at 1:1:1 ratio tested were 0.5
      and 0.8, respectively, indicating synergistic antiviral effects. No apparent
      cytotoxicity effects were observed with any of the combinations tested.
      CONCLUSION: These promising in vitro data warrant clinical investigation of the
      nucleosides analogues such as 2'-C-MeC or 2'-F-C-MeC in their prodrug forms,
      together with IFN-alphac2b and RBV, for successful treatment of HCV infections.

PMID- 18610556
TI  - Antiviral activity of geneticin against bovine viral diarrhoea virus.
AB  - BACKGROUND: Aminoglycoside G418 is commonly used to generate stable replicons for
      RNA viruses, such as hepatitis C virus, West Nile virus, and bovine viral
      diarrhoea virus (BVDV). This precludes testing 6418's own antiviral activities
      against those viruses. Here, we report antiviral activity of 6418 against BVDV.
      METHODS: Cell viability and virus yield reduction assays were used to investigate
      antiviral effects of G418 against BVDV. The expression of viral proteins and RNA
      were determined by western blot and real-time quantitive PCR, respectively.
      RESULTS: We demonstrated that G418 (50% cytotoxicity concentration of 400
      microg/ml) improved cell viability of Madin-Darby bovine kidney cells infected
      with a cytopathic strain of BVDV (NADL) in a dose-dependent manner with 50%
      effective concentration of 4 microg/ml. Interestingly, close structural analogues
      with known properties as translation inhibitors similar to G418 - kanamycin and
      gentamicin - had no antiviral activity against BVDV. In addition, 6418 inhibits
      virus yield of two different strains of BVDV (NADL and NY-1) without affecting
      viral RNA replication and translation or viral NS3 protein processing.
      CONCLUSION: Our data indicate that antiviral activity of G418 could result from
      interference with either the assembly or release of active virus, rather than the
      regulation of viral translation and replication. Thus, we propose the use of
      chemical analogues of G418 as antiviral therapeutics for treatment of viral
      diseases associated with the Flaviviridae family, such as hepatitis C virus,
      dengue virus, yellow fever virus, West Nile virus and others.

PMID- 18610557
TI  - Synthesis and evaluation of N-substituted acridones as antiviral agents against
      haemorrhagic fever viruses.
AB  - BACKGROUND: In the present study, a series of N-substituted acridone derivatives
      was synthesized and evaluated against two haemorrhagic fever viruses (HFV).
      METHODS: Compounds were tested against Junin virus (JUNV), an arenavirus agent of
      Argentine haemorrhagic fever, and dengue virus (DENV), a flavivirus agent of the
      most prevalent arthropod-borne viral disease in humans. RESULTS: Among tested
      compounds, two N-allyl acridones (derivatives 3c and 3f) elicited a potent and
      selective antiviral activity against JUNV (strain 1V4454) and DENV-2 (strain NGC)
      with 50% effective concentration values between 2.5 and 5.5 microM, as determined
      by virus yield inhibition. No cytotoxicity was detected at concentrations up to
      1,000 microM, resulting in selectivity indices >181.8-400.0. Both acridones were
      effective against a wide spectrum of arenaviruses and the four serotypes of DENV.
      Furthermore, 3c and 3f failed to inactivate virus before cell infection as well
      as to induce a refractory state by cell pretreatment, indicating that the
      inhibitory effect was exerted through a blockade in virus multiplication during
      the infectious process. CONCLUSION: These data are the first demonstration that
      acridone derivatives have a potent antiviral activity that block in vitro
      multiplication of HFV belonging to Arenaviridae and Flaviviridae, such as JUNV
      and DENV.

PMID- 18610558
TI  - [Unilateral self-awareness].

PMID- 18610559
TI  - [Truce on complaints, an analysis, please!].

PMID- 18610560
TI  - [Certainty produces nursing quality].

PMID- 18610561
TI  - [This is how one works towards health].

PMID- 18610562
TI  - ["We invest heavily in security". Interview by Urs Luthi].

PMID- 18610564
TI  - [Bringing health policy back on track].

PMID- 18610563
TI  - [Objective understanding of and therapy for nutritional defects].

PMID- 18610566
TI  - [The twelve nursing balms].

PMID- 18610565
TI  - [Maintaining anesthesiology standards is crucial].

PMID- 18610567
TI  - [Symptom management in HIV infections].

PMID- 18610568
TI  - [Hospitals: places of high risk].

PMID- 18610569
TI  - ["In vivo" measures of nursing quality].

PMID- 18610570
TI  - [Nurses at the center of patient security].

PMID- 18610571
TI  - [Better care for immigrants].

PMID- 18610572
TI  - [The first "State School" reaches 100 years].

PMID- 18610573
TI  - [Being with a teenager who cannot sleep].

PMID- 18610574
TI  - [Health occupations].

PMID- 18610575
TI  - [50th anniversary of the Polish Biochemical Society].

PMID- 18610576
TI  - [BD free flow electrophoresis system].

PMID- 18610577
TI  - [Biotechnology-from science to business].

PMID- 18610578
TI  - [Intellectual property in natural sciences].
AB  - The way from scientific finding through invention to production line and finally
      to the consument is long and expensive and patent should be taken into account.
      This is evident because the investment connected with the new application needs
      clear definition of intellectual property rights. Independently what we
      personally think about patenting in nature sciences--this is a common practice
      around the world. The positive and negative parameters of patenting are focus on
      biotechnology. The development of biotechnology is a cumulative effect of co
      operation of several disciplines: biology, biochemistry, chemistry, engineering,
      genetics, medicines and pharmacy and many more. Between not cited here is law and
      consequently the needs of cooperation between researchers and lawyers. There are
      several barriers in this co-operation, for example: nomenclature as well as the
      way of thinking. These borders could be pass only with intercommunication and
      cross-understanding. The dialog and transfer of knowledge is a must for
      understanding the nomenclature, terminology of nature by lawyers and by
      researchers in case of law. Polish legislation concerning intellectually rights
      is regulated by the law "Prawo wlasnosci przemyslowej" (30 June, 2000; Dz. U.
      2003, Nr 119, pos. 1117, with later amendments). This legislation is related to
      European Union directives and Munich Convention. Accordingly patenting of product
      and process is possible in Poland. However, the procedure is time and money
      consuming, particularly in the case of patent submission in several countries.
      Amendment of the Polish law to biotechnology made possible patenting of living
      organism and their parts. It is worth to stress that patented inventions can be
      used free of charge for research and teaching.

PMID- 18610579
TI  - [Multidrug resistance in fungi].
AB  - Antibiotic and synthetic chemotherapeutic resistance in pathogenic yeast becomes
      one of the biggest challenges for the modern chemotherapy. An increasing number
      of pathogenic yeast and filamentous fungi resistant to the action of the majority
      of currently used drugs is isolated in clinics nowadays. Among variety of the
      resistance mechanisms, the most dangerous grows to be the multidrug resistance.
      The most important mechanism of the multidrug resistance is the overexpression of
      membrane proteins participating in the active efflux of drugs out of the cells
      subjected to chemotherapy. Representatives of two classes of multidrug efflux
      transporters, ABC and MFS, have been identified in fungi. One of the most
      important strategies for overcome the phenomenon of multidrug resistance in
      pathogenic fungi, is the use of chemical compounds co-administrated with
      chemotherapeutics which are able to restore drug susceptibility in multidrug
      resistant cells. Mode of action of these chemical compounds may be very diverse,
      from the substrate competition, through the influence on the membrane fluidity,
      to the multidrug transporters activity modulation. This paper presents a review
      of the current knowledge on proteins contributing to fungal multidrug resistance
      and strategies for overcoming multidrug resistance by pharmacological
      intervention.

PMID- 18610580
TI  - [Natriuretic peptides--their receptors and role in cardiovascular system].
AB  - Natriuretic peptides belong to a family of small proteins that play a major role
      in modulation of natriuresis, diuresis and vasodilatation. They counteract the
      activity of renin-angiotensin-aldosterone system. They are also involved in the
      regulation of homeostasis, fat metabolism and long bone growth. Natriuretic
      peptides family in mammals consists of three main members: atrial natriuretic
      peptide (ANP) - secreted by the atrial myocardium; brain natriuretic peptide
      (BNP)--secreted mainly by the ventricular myocardium, and C-type natriuretic
      peptide (CNP)--produced and released by endothelial cells. Secretion of these
      peptides is stimulated by atrial and ventricular distension, increased blood
      pressure, hypoxia or renal dysfunction. Natriuretic peptides play their roles via
      interactions with NPR-A and NPR-B receptors which are transmembrane guanylyl
      cyclases. Their local concentrations, regulated by internalization and
      degradation, are mediated by the NPR-C receptor and by neutral endopeptidase. The
      paper presents the current knowledge of structure and biological function of
      natriuretic peptides.

PMID- 18610581
TI  - [DNA replication fidelity].
AB  - DNA replication fidelity plays fundamental role in faithful transmission of
      genetic material during cell division and during transfer of genetic material
      from parents to progeny. Replicative polymerases are the main guardian
      responsible for high replication fidelity of genomic DNA. DNA main replicative
      polymerases are also involved in many DNA repair processes. High fidelity of DNA
      replication is determined by correct nucleotide selectivity in polymerase active
      center, and exonucleolytic proofreading that removes mismatches from primer
      terminus. In this article we will focus on the mechanisms that are responsible
      for high fidelity of replications with the special emphasis on structural studies
      showing important conformational changes after substrate binding. We will also
      stress the importance of hydrogen bonding, base pair geometry, polymerase DNA
      interactions and the role of accessory proteins in replication fidelity.

PMID- 18610582
TI  - [Adeno-associated viruses (AAV)].
AB  - Recombinant adeno-associated virus derived vectors (rAAV) a thought to be a most
      promising candidates for gene therapy applications. Their nonpathogenic nature as
      well as the encouraging capability to infect both proliferating and non
      proliferating cells are advantages for gene therapy applications. Here, we
      summarize the potential mechanisms responsible for AAV maintenance and site
      specific integration to human genome. The role of Rep proteins, inverted terminal
      repeats and p5 promotor sequences for chromosomal incorporation of AAV are
      discussed. Making the site-specific integrative recombinant AAV vectors for gene
      therapy seems to be closely dependent on the development of viral vectorology.

PMID- 18610583
TI  - [CCT chaperonins and their cochaperons].
AB  - Chaperonins are large oligomers consisting of two superimposed rings, each
      enclosing a cavity used for the folding of other proteins. They have been divided
      into two groups. Chaperonins of type I were identified in mitochondria and
      chloroplasts (Hsp60) or bacterial cytosol (GroEL) as well. Chaperonins type II
      were found in Archea and the eukaryotic cell cytosol (CCT). Protein folding
      occurs in the chaperonin after its conformational changes induced upon ATP
      binding. Mechanism of the protein folding, although still poorly defined, clearly
      differs from the one established for GroEL. Although CCT with prefoldin seems to
      be mainly involved in the folding of actin and tubulin, other substrates engaged
      in various cellular processes are beginning to be characterized, including
      proteins possessing WD40-repeats. Moreover, several lines of evidence suggest
      that beside prefoldin, CCT may work in concert with phosducin-like proteins
      (PhLPs).

PMID- 18610584
TI  - [The role of mitochondrial permeability transition pore in physiology and
      pathology of the cell].
AB  - Mitochondrial megachannel, a multiprotein complex, is localized in close contacts
      of the outer and the inner mitochondrial membranes. It plays important role in
      many aspects of cell physiology and its opening can have different consequences.
      This review summarizes the present knowledge about structure and function of the
      megachannel in the cell.

PMID- 18610585
TI  - [Expression of bone morphogenetic proteins, matrix metalloproteinases and
      inhibitors of matrix metalloproteinases in lung cancers and their prognostic
      significance].
AB  - Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are one of the
      molecules that have become a topic of great interest among scientists studying
      lung cancers. There is a distinct tendency toward higher expression of selected
      MMP and TIMP in tumor lung tissue. Furthermore, there is a significant
      correlation between high expression of TIMP-1 or MMP-2 in lung cancer and
      shortened survival and between high expression of TIMP-1 or MMP-7 in lung cancer
      and higher stage of disease. There have been only a few articles about the role
      of bone morphogenetic proteins (BMP) in lung cancer pathogenesis published so far
      in which BMP-2 or BMP-4 were overexpressed. It was also shown that BMP-2
      stimulates tumor growth while BMP-4 inhibits it. This article is mainly
      concentrated on the expression of MMP, TIMP and BMP in lung cancers, but also it
      shows the significance of these proteins.

PMID- 18610586
TI  - [Mechanisms that protect against homocysteine toxicity].
AB  - Elevated concentrations of homocysteine (Hcy) in human tissues have been
      correlated with some diseases, such as cardio-vascular, neurodegenerative, and
      kidney disorders. Hcy occurs in human blood in several forms. The most reactive
      is homocysteine thiolactone (HcyTl). It spontaneously homocysteinylates proteins
      impairing their functions. As has been evidenced recently, organisms developed
      protective mechanisms against the HcyTl toxicity. The first mechanism discovered
      was the calcium-dependent enzyme occurring in mammalian sera, known till then as
      paraoxonase, which hydrolyzes HcyTl to Hcy. Chronologically second mechanism
      discovered was urinary excretion of HcyTl. The third protective mechanism is the
      HcyTl hydrolysis catalyzed by intracellular enzyme known as bleomycin hydrolase.
      This review outlines current knowledge of the Hcy toxicity and of the three
      aforementioned protective mechanisms, emphasizing the role of bleomycin
      hydrolase/ homocysteine-thiolactonase.

PMID- 18610587
TI  - [Ethylene signal transduction pathway].
AB  - Ethylene is involved in the regulation of many growth and developmental processes
      in plants. Signaling pathways of the hormone are activated by five receptors,
      which are localized in membranes of endoplasmic reticulum and are similar to
      bacterial two-component histidine kinases. In the air, ethylene receptors
      activate CTR1 protein, which is a negative regulator (repressor) of nuclear
      protein--EIN2. In turn, EIN2 is an activator of transcriptional factors cascade
      responsible for the regulation of the expression of ethylene response genes. The
      level of EIN3, as well as other elements of ethylene signal transduction pathway,
      is subjected to complicated regulations on transcriptional and posttranslational
      levels, in which other internal and environmental factors are involved.

PMID- 18610588
TI  - [DNA microarrays--perspective of application for drug effectivity and safety
      evaluation].
AB  - Microarray technology provides a unique tool for the determination of gene
      expression at the level of messenger RNA (mRNA). Microarray has been successfully
      applied to the high throughput simultaneous expression of many thousands of genes
      in a single experiment. One important application of DNA microarray technology,
      within the context of drugs effectiveness and safety evaluation studies, is its
      use as a screening tool for the identification of biochemical pathways, potential
      targets for novel molecular therapeutics, for the identification of molecular
      mechanisms of toxicity and to understand and predict individual drug sensitivity
      and resistance. The purpose of this review is presentation of the utility of DNA
      microarray technology in all phases of the drug discovery process.

PMID- 18610589
TI  - Over the past few years, the government has sought to make health care more
      transparent.

PMID- 18610590
TI  - The practice of locum tenens: views of a senior surgeon.

PMID- 18610591
TI  - Measuring patient experiences of care.

PMID- 18610592
TI  - Building a successful residency program: insights from an award-winning program
      director.

PMID- 18610593
TI  - Photos shed light on history of surgery in Mexico.

PMID- 18610594
TI  - Joint Commission designated to improve safety of office-based surgery.

PMID- 18610595
TI  - Pedal to the metal.

PMID- 18610596
TI  - [A method to evaluate femoral bone mass in rats with CT numbers].
AB  - To develop a method of evaluating bone mass with CT numbers (Hounsfield unit,
      HU), volumetric mean of CT numbers (HUm) was defined to describe bone mass for
      the study of bone loss caused by microgravity. Ten femurs in the tail-suspended
      rats experiment were scanned by CT scanner. And the RUm of the intact, proximal,
      middle and distal femurs were obtained from these CT data. Then regressive
      analysis was performed between HUm and bone mineral density (BMD) measured by DXA
      in those regions. When HU threshold is equal to 400, the correlation between BMD
      and HUm of the intact femur is the best in all cases (R = 0.887, P <0.001), and
      the correlation between BMD and HUm of the proximal femur (R = 0.833, P <0.01) is
      better than those of the middle femur (R=0.683, P<0.05) and distal femur (R =
      0.744, P<0.05). Volumetric mean of CT numbers has a good linear relationship with
      BMD; it can accurately describe bone mass and can be used to evaluate the results
      of the tail-suspended rats experiment.

PMID- 18610597
TI  - [Computer aided design and manufacturing of the framework of PFM fixed bridge].
AB  - We have carried out a research on the method for Computer Aided Design and
      Manufacturing (CAD/ CAM) of the framework of porcelain-fused-to-metal(PFM) fixed
      bridge. Taking the missing of the mandibular first molar as an example, firstly,
      we used ATOS II 3D scanner to collect the 3D data of the abutment teeth and used
      the acquried data to design the coping crowns. Secondly, the relevant standard
      bridge was selected from the standard bridges database and was deformed
      inaccordance to the characteristic of the patient. Then it was set to the correct
      position between the coping crowns automatically based on the restricting lines
      and faces. Finally, the connector was designed to connect the coping crowns and
      the bridge based on the touching area. The final product was manufactured by 3
      axis NC milling machine. The results of examination showed that the framework of
      PFM fixed bridge fitted the abutment teeth very well, and the hardness of the
      connector and the precision of the whole model were feasible and reasonable. The
      method of designing and manufacturing the framework of PFM fixed bridge from
      CAD/CAM is practicable, efficient and accurate. It is also an important part of
      homemade dental CAD/CAM system.

PMID- 18610598
TI  - [Application of integer lifting wavelet transform and subblock coding to medical
      image compression].
AB  - The method of subblock coding for medical image compression is presented by means
      of the integer lifting wavelet transform. The integer lifting wavelet transform
      has better effects on improving the processing speed; it can achieve wavelet
      transform for arbitrary size image and accomplish the transform at current
      position; furthermore, it can save memory space. The lifting algorithm can deal
      with the lossless compression and loss compression of image simultaneously, so it
      is adapted to telemedicine system and medical image compression system. The
      compression method based on image subblock coding can not only realize
      controlling BR (bit ratio), but also realize SNR (signal noise ratio) and suit
      for progressive transform.

PMID- 18610599
TI  - [A strategy of ECG classification based on SVM].
AB  - Electrocardiogram (ECG) signal is important for physician to diagnose diseases.
      Various existing techniques on ECG classification have been reported. Generally,
      these techniques classify only two or three arrhythmias and need significantly
      long processing time. A new algorithm based on Support vector machine (SVM) is
      presented to solve the problem in this paper, which has been successfully applied
      to the classification of ECG. And in this paper are clarified the fundamental
      ideas of the classification of ECG based on SVM. Compared with the traditional
      neural network, this method is superior to it in theory. Because this new method
      deals with the minimization of the test samples, not the training samples.

PMID- 18610600
TI  - [Research on analytical methods of phase synchronization in EEG].
AB  - Synchronous brain activities are regarded as the indicator of the functional
      integration of the brain. Based on the physiological mechanism of synchronous
      activity, the detection process and research on quantification methods concerning
      synchronization are explained. Conventional and modern signal processing
      approaches, such as time analysis, frequency analysis, Hilbert transform (HT),
      especially wavelet transform (WT), are applied to EEG (electroencephalograph)
      synchronization study. Simulation data and real data are utilized to test the
      methods mentioned above, which prove the usefulness and validity of methods.
      According to the final results, Hilbert analysis is better for its authenticity.

PMID- 18610601
TI  - [Detrended fluctuation analysis of epileptic rat EEG].
AB  - Detrended fluctuation analysis (DFA) is a new technique used to characterize the
      long-range temporal correlation (LRTC) structure of non-stationary time series,
      which has been applied in electroencephalographic (EEG) oscillations and diseases
      such as Alzheimer and stroke. In this paper, DFA is used to study the scaling
      exponents of intracranial EEG recordings of Pilocarpine-induced epileptic rat. It
      was found that when the brain functional status changed from non-epileptiform
      discharges to continuous-epileptiform discharges and to period-epileptiform
      discharges, the average scaling exponents of four brain regions (left cortex and
      left hippocampus, right cortex and right hippocampus) changed from 0.97 to 0.82
      and to 0.94, and a statistically significant difference between the brain
      functional states was shown by paired T test (P < 0.05), thus suggesting that the
      local neuronal network dynamics of the three brain function states may be
      different. But in regard to the three brain function states, there is no
      statistically significant difference between the four brain regions(P >0.05).

PMID- 18610602
TI  - [Protein secondary structure prediction based on maximum entropy model].
AB  - Secondary structure prediction plays an important role in function prediction of
      protein. In this paper, maximum entropy model is used to predict protein
      secondary structure. We build feature function sets based on the influential
      factors which are crucial to the states of secondary structure of residues in
      protein sequence. Multi-factors are taken into account in the model, including
      charge of amino acids, conformational parameter for the states of secondary
      structure, short and long ranges of interaction of residues in sequence. As such,
      multi-source information is integrated into a single probability model by the
      method. Compared with the reported methods, our method gets a higher accuracy
      rate in predicting protein secondary structure. The results demonstrate that the
      proposed method is practical.

PMID- 18610603
TI  - [Optimization approach to inverse problems in near-infrared optical tomography].
AB  - In this paper, we introduce an optimization approach to the inverse model of near
      infrared optical tomography (NIR OT), which can reconstruct the optical
      properties, namely the absorption and scattering coefficients of thick tissue
      such as brain and breast tissues. A modeling and simulation tool, named Femlab
      and based on finite element methods, has been tested wherein the forward models
      are based on the diffusion equation. Then the inverse model is soved; this is
      regarded as an optimization approach, including the tests on difference between
      the measured data and the predicted data, and the optimization methods of optical
      properties. The algorithms used for optimization are multi-species Genetic
      Algorithms based on multi-encoding. At last, the whole strategy for the Femlab
      and optimization approach is given. The strategy is proved to be sufficient by
      the simulation results.

PMID- 18610604
TI  - [The influence of using simplified model for beamlet dose calculations in IMRT
      treatment planning and the approaches to diminish the influence].
AB  - Simplified dose calculation model with high computation efficiency is often used
      to generate the dose matrices for beamlets in the inverse planning of the
      intensity modulate radiation therapy. It is likely that this simplification could
      degrade the quality of the final treatment plans. This paper is aimed at testing
      the influence of such simplification in dose calculations of beamlets and
      accordingly proposing methods to avoid severe degradation of the plans. Two
      simulation instances were adopted. The primary dose calculation model without
      involvment of scattering effect was used to generate the dose matrices of
      beamlets. The differential convolution superposition dose calculation model that
      well accounts for scattering effect was used to calculate the final dose
      distributions for given intensity profiles. It is found that the simplification
      in dose matrices of beamlets degrades the dose levels in the edge area of the
      targets, however, the degradation could be diminished or even avoided by adding a
      suitable margin around the targets or by using the multiple-shifted-beamlet
      matrices (MSBM) method that was proposed in our previous paper.

PMID- 18610605
TI  - [An EMD based epileptic spike detection method].
AB  - The automatic spike detection in EEG is significant in both diagnosing illness
      and alleviating the heavy labour force of the doctor. This paper proposes a new
      EMD based method to complete spike detection. It decomposes a signal into a few
      intrinsic mode functions (IMF), and then applies the nonlinear energy operator
      (NEO) to the first IMF to complete the automatic detection. Sufficient results
      are obtained by applying this method to the spike detection of the simulation
      signal and the real epileptic EEG signal.

PMID- 18610606
TI  - [On skull recognition of quadratic rational Bezier curve fitting].
AB  - Skull recognition is a new method of biometrics recognition. A skull recognition
      algorithm is presented in this paper by Quadratic rational Bezier curve fitting
      which accurately describes the feature of skull edge; the experiment results
      based on skull x-ray image show the correctness of this method.

PMID- 18610607
TI  - [Quantitative functional evaluation on right ventricle with auto-segmentation and
      three-dimensional reconstruction].
AB  - The authors first segment the right ventricle regions from the echocardiographics
      by introducig a seeded region growth algorithm. Then they reconstrunct the three
      dimensional data field of right ventricle by using rotary scanning interpolation
      algorithm. And then, the authors propose a layer-by-layer, row-by-row, and voxel
      by-voxel approach based on the interpolation results to estimate the volume of
      right ventricle. Finally, some right ventricle functional parameters such as EDV
      (End-diastolic volume), ESV (End-systolic volume), and RVEF (Right ventricular
      ejection fraction) are computed according to the volume results. The volume
      variation curves of several patients during a cardiac cycle have been
      successfully plotted out. The obtained results are compared with those from
      Tomtec medial image workstation. The comparison indicates the proposed approach
      is practical and meaningful.

PMID- 18610608
TI  - [Preliminary design for a VI system combining the voice acoustic analyzing and
      glottal image analyzing].
AB  - This work is directed at developing a virtual instrument system as an accessorial
      diagnostic instrument for laryngeal diseases. Programmed with LabWindows/CVI, the
      system combines the voice acoustic analyzing function with the glottal image
      measuring function. The voice acoustic analyzing system can sample, store and
      replay vocal signals; can extract and analyze parameters, including fundamental
      frequency (F0), frequency perturbation quotient (FPQ), amplitude perturbation
      quotient(APQ), harmonics-to-noise ratio (HNR), jitter frequency (JF), Shimmer;
      and can do 3D sound graph analysis. The glottal image analyzing system can sample
      and store the image observed by the laryngostroboscope; can display any phase in
      one cycle of the vibration of the vocal cords or a slow and continuous movement
      of vibrating vocal cords; can snap and save the diagnostic frame of image; and
      can extract the parameters of the image such as the length and area of the
      glottis, the length and area of the vocal cords and the diseased part.

PMID- 18610609
TI  - [Medical knowledge discovery system research based on computer--epidemiological
      data mining of complications in diabetes mellitus].
AB  - In this paper, a systematic architecture of medical data mining based on computer
      was provided for epidemiological analysis. Complications in diabetes mellitus
      were used as the cases under discussions on redundancy elimination, normalized
      storage, knowledge induction and visual expression of medical data. 3022 pieces
      of census records from Tianjin General Hospital were researched to find the
      solution of quantitative mining from qualitative data and knowledge discovery.
      From the qualitative data mining of 43 kinds of complications in diabetes
      mellitus, we found 18 knowledge rules with significant statistical meaning on
      concurrency relation, e. g. hyperlipoidemia, coronary disease, hypertension and
      cerebrovascular disease. And knowledge tree was noted to be an effective visual
      expression method for showing the rules generated from the above system. Medical
      analysis system based on data mining and knowledge discovery could generate
      effective knowledge rules from medical record database, which was found to be
      especially useful for epidemiological analysis and national health survey. So how
      to cooperate with community medical care and hospital information system in the
      near future is practically significant.

PMID- 18610610
TI  - [Design and implementation of projection-initialized wall filter in ultrasonic
      imaging].
AB  - Wall filtering is a key technology in ultrasound color flow imaging system.
      Without efficient suppression of wall signal originating from stationary and
      moving tissue, low velocity blood flow cannot be measured, and the estimates of
      higher velocities will have a large bias. Among the various wall filters, the
      projection-initialized infinite impulse response (IIR) wall filter has narrow
      transition bandwidth and high stopband suppression ratio; it is superior to other
      wall filters. At present, the related literatures are only limited to theoretical
      research on this kind of filter, and no feasible design and implementation
      methods are reported. In this paper, a new design and implementation scheme for
      the projection-initialized filter is proposed, which transforms the filtering
      process to matrix multiplications. The proposed scheme is realized on
      programmable logic devices. Experimental results show that it is a simple and
      effective implementation method for projection-initialized IIR filter, and it is
      superior to conventional wall filters.

PMID- 18610611
TI  - [CT image segmentation based on automatic adaptive minimal fuzzy entropy
      measure].
AB  - In order to extract the anatomical feature of several tissues from CT image and
      solve the contradiction between the improvement of searching speed and the
      instability of results,we propose a method for image segmentation using auto
      adaptive minimal fuzzy entropy measure. Firstly, to find the optimal threshoding
      for segmenting image, the values of the exponent parameters of membership
      function of fuzzy subsets and the range of the searching thresholding values can
      be determined by using the iterative approach and the image histogram, and then
      the thresholding of minimizing the fuzzy entropy is implemented by searching all
      possible combinations of every thresholding in determinate searching range. The
      experiment results show that our proposed method facilitates good performance for
      CT image segmentation. The searching speed is quick, the segmented images show
      more details, and the results of many runs are steadier than those obtained by
      using genetic algorithm or simulated annealing algorithm.

PMID- 18610612
TI  - [Research on an adaptive fetal electrocardiograph based on DSP].
AB  - This paper introduces the research and realization of an adaptive fetal
      electrocardiograph (FECG). We have developed an embedded system which takes the
      digital signal processor chip TMS320LF2407A as the core. According to the
      principle of adaptive noise cancelling(ANC), the ANC software algorithm is
      studied and realized to extract the FECG by non-invasive means, then the embedded
      system sends the data to the computer through the communication interface for
      real-time display, analysis and recording of the processing results. The
      experiments indicate that the design is reasonable and the instrument owns a good
      performance.

PMID- 18610613
TI  - [A blood speckle reduction method based on wavelet transform of intravascular
      ultrasound].
AB  - Intravascular ultrasound (IVUS) has been applied into the diagnosis of coronary
      heart disease and the relevant intervention therapy more and more widely.
      However, the frequency of ultrasound must be increased in order to improve the
      resolution of images, which makes the blood speckle noise increase
      significantly,decreases the contrast of lumen and arterial wall structure,
      increases the difficulty to discriminate arterial wall from structures, and makes
      it inconvenient to diagnose and treat illness. In this paper a wavelet shrinkage
      method based on local threshold is introduced to reduce blood speckle noise.
      Results show that the method can remove the speckle noise, keep the edges of
      image, increase the contrast, and thus is helpful to the identification of the
      arterial wall and the tissues around.

PMID- 18610614
TI  - [Detecting sleep apnea/hypopnea events with a wearable respiratory inductive
      plethysmograph system].
AB  - The wearable respiratory inductive plethysmograph(RIP) system is a non-intrusive
      respiratory monitoring system. Sleep monitoring was performed on 9 human subjects
      suspected of having sleep apnea hypersomnolence syndrome (SAHS) and 7 healthy
      volunteers using both the wearable RIP system and the conventional
      polysomnography(PSG), and the sensitivity and specificity of the wearable RIP
      system were analyzed by comparison with the PSG results. According to the
      characteristic of the wearable RIP system in detecting sleep apnea/hypopnea
      event, the diagnostic criteria of sleep apnea/hypopnea event were put forward.
      All subjects with SAHS diagnosed by the wearable RIP were confirmed by PSG,the
      sensitivity and specificity of the wearable RIP system for detecting sleep
      apnea/hypopnea events were 99.0% and 94.6% respectively. The wearable RIP system
      can be used reliably in detecting sleep apnea/hypopnea events. This system can be
      used at home for detecting the sleep apnea/hypopnea events non-intrusively.

PMID- 18610615
TI  - [A method based on wavelet package transform for denoising electromyographic
      signal].
AB  - The detection and analysis of electromyographic signal is of far reaching
      importance for clinical diagnosis as well as for convalescence medicine.
      Electromyographic signal is a kind of biological signal in the background full of
      noise, so it is somewhat difficult to detect and extract the electromyographic
      signal. In this paper is discussed how to use the method of wavelet package
      transform to denoise the electromyographic signal on the basis of its feature and
      its relationship with noise. The results of simulation and application in the
      Electromyographic Evoked Potential Measuring System independently developed by
      our laboratory illuminate that the method is effective for denoising
      electromyographic signal.

PMID- 18610616
TI  - [Study of dopamine transporter imaging on the brain of children with autism].
AB  - This study was conducted to evaluate the applicability of 99mTc-2beta-[ N, N'-bis
      (2-mercaptoethyl) ethylenediamino]methyl,3beta(4-chlorophenyl)tropane(TRODAT-1)
      dopamine transporter(DAT) SPECT imaging in children with autism, and thus to
      provide an academic basis for the etiology, mechanism and clinical therapy of
      autism. Ten autistic children and ten healthy controls were examined with 99mTc
      TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was
      calculated with region of interest analysis according to the ratics between
      striatum and cerebellum [(STR-BKG)/BKG]. There was no statistically significant
      difference in semiquantitative dopamine transporter between the bilateral striata
      of autistic children (P=0.562), and between those of normal controls (p=0.573);
      Dopamine transporter in the brain of patients with autism increased significantly
      as compared with that in the brain of normal controls (P=0.017). Dopaminergic
      nervous system is dysfunctioning in the brain of children with autism, and DAT
      99mTc-TRODAT-1 SPECT imaging on the brain will help the imaging diagnosis of
      childhcod autism.

PMID- 18610617
TI  - [Wolff's law-based continuum topology optimization method and its application in
      biomechanics].
AB  - A new method for the simulation of the mass distribution of cancellous bone is
      presented on the basis of finite element analysis (FEA). In this method,the
      process of bone remodelling is considered as a process of the topology
      optimization of a corresponding continuum structure. Fabric tensor is used to
      express the microstructure and the constitutive properties of cancellous bone.
      The effective volume fraction or the relative density of a point in the design
      domain is expressed by the invariables of the fabric tensor. A reference strain
      interval, which is corresponding to the strain dead zone of a bone in
      biomechanics, is applied to detect the the final topology of the structure. By
      the present approach, several numerical results are given, i. e., the simulation
      on the shape of the coronal plane of vertebrae, the predictions of the mass
      distributions of the two-dimensional and the three-dimensional proximal femurs.
      The validity and feasibility of this new method are verified by the comparison
      between the results of the present work and those in the published literatures.

PMID- 18610618
TI  - [Effects of ligaments and plantar fascia on the foot finite element analysis].
AB  - Some 3D finite element systemic models are currently established and used to
      simulate the foot biomechanical state. However, during most of these 3D foot
      finite element static analyses, ligaments and plantar fascia are generally
      defined by connecting the corresponding attachment points on the bones, and the
      spaces between the bones are fused together by solid elements with given
      cartilage stiffness to simulate the connection of bones. This "connection of
      bones" takes the place of the real interactions between neighbored bones and
      enhances the structure of foot, which possibly leads to the result that the
      effects of ligaments and other soft tissues are completely replaced by the effect
      of articular cartilages. Thereby, ligaments and other soft tissues maybe not play
      an inherent role in the finite element analysis. The objective of this study was
      to estimate whether there exists the effect of ligaments and plantar fascia on
      the biomechanical behaviors of the foot tissue stress distribution and foot
      structure deformation during the balanced standing stance and static finite
      element analysis.

PMID- 18610619
TI  - [A new three-point bending test for bone biomechanical properties of rat's
      tibia].
AB  - In this study, we compared the three-point bending test of the metaphyseal tibia
      versus the three-point bending test of the diaphysial tibia in rats. Twenty 6
      month-old female Sprague-Dawley rats were randomly divided into the
      ovariectomized (OVX) group and the sham-operated (Sham) group. All rats were
      housed in standard environmental conditions. Five months after operation, all
      rats were sacrificed by depletion method. All left tibia were removed for the
      three-point bending test. The changes of mechanical parameters were examined by
      the three-point bending test of the metaphyseal tibia and by that of the
      diaphysial tibia. Elastic, Maximum Load, Maximum Stress, Failure Load, and
      Failure Stress of the metaphyseal tibia were much lower in OVX rats than in Sham
      rats. However, there was no statistically significant difference in all of the
      mechanical parameters of the diaphysial tibia between the OVX group and the Sham
      group. The new three-point bending test of the metaphyseal tibia is much more
      sensitive and useful as compared with the test of the diaphysial tibia in
      evaluating the changes of mechanical properties of tibia in osteoporotic rats.

PMID- 18610620
TI  - [Influences of graft diameter on the blood flow in 2-way bypassing surgery].
AB  - The graft diameter plays a critically important role in the long-term patency
      rates of bypass surgery. To clarify the influence of graft diameter on the blood
      flows in the femoral 2-way bypass surgery, the physiologically pulsatile flows in
      two femoral bypass models were simulated with numerical methods. For the sake of
      comparison, the models were constructed with identical geometry parameters except
      the different diameters of grafts. Two models with small and large grafts were
      studied. The boundary conditions for the simulation of blood flow were constant
      for both models. The maximum Reynolds number was 832.8, and the Womersley number
      was 6.14. The emphases of results were on the analysis of flow fields in the
      vicinity of the distal anastomosis. The temporal-spatial distributions of
      velocity vectors, pressure drop between the proximal and distal toe, wall shear
      stresses, wall shear stress gradients and oscillating shear index were compared.
      The present study indicated that femoral artery bypassed with a large graft
      demonstrated disturbed axial flow and secondary flow at the distal anastomosis
      while the axial flow at its downstream of toe was featured with larger and more
      uniform longitudinal velocities. Meanwhile, the large model exhibits less
      refluences, relatively uniform wall shear stresses, lower pressure and smaller
      wall shear stress gradients, whereas it does not have any advantages in the
      distributions of secondary flow and the oscillating shear index. In general, the
      large model exhibits better and more uniform hemodynamic phenomena near the
      vessel wall and may be effective in preventing the initiation and development of
      postoperative intimal hyperplasia and restenosis.

PMID- 18610621
TI  - [Effects of frictional properties on traumas of rabbit skin].
AB  - Simulative experiments on skin traumas between prosthetic socket materials and
      residual limb skin were investigated by using the means of tribology, histology
      and animal experiment. Healthy adult rabbits were used as animal model and their
      denuded back skin was selected as experimental position to simulate residual limb
      skin. The effects of different normal load and reciprocal sliding frequency on
      rabbit skin trauma grade were investigated by using a reciprocal sliding skin
      friction testing apparatus to simulate prosthesis gait. The traumatic
      subcutaneous tissue slice was stained with hematoxylineosin and the morphology
      was observed under the optical microscope. The scab thickness of traumatic skin
      was measured under x 10 object lens. The inflammatory cells were counted in a
      given visual field under x 20 object lens. The statistical significance analysis
      of scab thickness and inflammatory cells were carried out to assess the effect of
      different frictional conditions on skin pathological traumas. The results showed:
      the greater normal load and higher reciprocal sliding frequency applied on the
      rabbit skin, the more serious injury to skin and more inflammatory cells in the
      subcutaneous tissue at the same time. The findings provide a theoretical basis of
      comfortized prosthesis design and gait analysis for the amputee.

PMID- 18610622
TI  - [Rac1 mediates the migration of endothelial cells induced by IL-8].
AB  - This study sought to elucidate whether Rac1 mediates the migration of endothelial
      cell induced by IL-8. The Transwell chamber motility assay was conducted to
      disclose the effect of different matrigel dilution and different time of IL-8
      treatment on the migration of endothelial cells. The mRNA of Rac1 was detected by
      RT-PCR. The results demonstrated that when the concentration of Matrigel was 1:2,
      there is significant difference on the amounts of migration cells than that of
      the concentration of 1:3 or 1:8; When the dilution of Matrigel was 1:4, 1:5 or
      1:6, there is no significant difference on the amounts of migration cells than
      that of other dilution groups. So we choose the Matrigel concentration as 1:4.
      With the increase of IL-8 stimulation time, the cells which migrated from upper
      reservoirs to lower reservoirs progressively increased. After six hours
      stimulation by IL-8, the expression of Rac1 mRNA in migrated cells was increased,
      compared with that of other groups. The results suggest that Rac1 may mediate the
      migration of endothelial cells induced by IL-8. It can also be the foundation for
      further investigation on the role of Rac1 in the migration of endothelial cells
      induced by IL-8.

PMID- 18610623
TI  - [Bone remodeling numerical simulation on the basis of bone adaptive theory].
AB  - In this paper, combined with the finite element (FE) method and optimization
      theory, a strain energy criterion is used to simulate and predict the bone
      remodeling. The strain energy density is taken as the mechanical stimulus. The
      bone remodeling is described as the changes of material distribution, which can
      represent the process of bone remodeling. By remodeling simulation of a two
      dimensional proximal femur, a three-dimensional proximal femur and bone fracture
      healing plastic process, we demonstrate that this criterion can produce a
      realistic apparent density distribution in the proximal femur, and this criterion
      can well illuminate the mechanism of bone fracture healing plastic process.

PMID- 18610624
TI  - [A novel system for tongue inspection based on hyperspectral imaging system].
AB  - Tongue inspection is an important diagnostic method in traditional Chinese
      medicine (TCM). However, due to its qualitative, subjective and experience-based
      nature, traditional tongue inspection has found very limited application in modem
      clinical medicine. In this paper, a novel system for tongue inspection based on
      hyperspectral imaging system is developed. The system includes image acquisition,
      feature extraction and classification functions. In this system, two kinds of
      quantitative features, spatial and spectral, are extracted from hyperspectral
      tongue images by using popular digital image processing techniques. Then,
      Bayesian networks are employed to model the relationship between these
      quantitative features and diseases. The preliminary results show that the system
      is sensitive to the abnormal tongues.

PMID- 18610625
TI  - [Design optimization of endovascular stent by finite element method].
AB  - Stent implantation is now the favorable therapy of coronary heart disease, but
      the restenosis occurring in association with the currently used stents device has
      become the main obstacle limiting the further development of stent. To change the
      expanding behavior of endovascular stents by way of design optimization is
      considered one of the effective approaches for reducing the damage to the intima
      of blood vessel and thereby decreasing the in-stent restenosis. So in this paper,
      the finite element method was used to systematically simulate and analyze the
      influences of different width of ring supporter and the non-symmetrical design of
      stent on its transitorily expanding behavior. The results show that among the
      structure parameters, the width of ring supporter of stent influences its
      expanded pressure remarkably. When designing the endovascular stent, we make its
      ring supporter unsymmetrical, i. e., we make the width of ring supporter of stent
      change degressively from its central part to end part. By this means, the
      dogboning, which normally happens in the expanding process of the balloon/stent
      system, can be effectively controlled and the acute vascular injuries can be
      reduced.

PMID- 18610626
TI  - [A novel nano-hydroxyapatite/aliphatic polyesteramide composite].
AB  - Hydrothermally synthesized nano-hydroxyapatite (n-HA) varying in weight from 10%
      to 30% was used as filler to make nanocomposites with novel aliphatic
      polyesteramide (PEA) in our laboratory. The structure and properties of PEA and
      its n-HA composites were investigated through transmission electron microscopy,
      infrared spectrometry, X-ray diffractioin, scanning electron microscopy and
      energy spectrometry. The shape and size of the n-HA crystals are similar to those
      of the apatite crystals in natural bone. Molecule interactions are present
      between the n-HA and PEA in the composite, which allows the uniform dispersion of
      n-HA in PEA matrix. This contributes enhanced mechanical property and bioactivity
      to the composite. The cytocompatibility of the composites has been investigated
      by culturing osteoblasts on the membranes. Good cell attachment and proliferation
      manner were observed on the membranes after 1 week. These results suggest that
      the PEA/n-HA composites prepared in this study may serve as potential candidate
      scaffold for tissue engineering.

PMID- 18610628
TI  - [Impact of immobilized RGD peptides on cell attachment of decellularized valve
      scaffolds].
AB  - This is a comparative study on three groups. With the help of a coupling reagent
      Sulfo-LC-SPDP, the biological valve scaffolds were surface modified with one of
      arginine -glycine -aspartic acid (RGD) containing peptides by covalent bond(the
      treated group). After rat aortic myofibroblast seeding, MTT test showed that more
      cells of the treated group attached on the valve scaffolds coupled with RGD
      peptides when compared with the cells of the coated group and untreated group.
      Moreover, correlatioins of attachment with attaching time and peptide
      concentrations were observed. Light and electron microscopy and cell count also
      confirmed the findings. Therefore, immobilizing the RGD peptides on the
      decellularized valve scaffolds is effective for improving cell attachment, which
      is helpful to constructing tissue engineering heart valve.

PMID- 18610627
TI  - [Effects of micropatterned surfaces coated with type I collagen on the
      orientation and growth of tenocytes].
AB  - It is crucial to improve the orientation and growth of cells on substrates in
      tissue engineering. In this study, we investigated the effects of micropatterned
      surfaces coated with type I collagen (CNI) on the orientation and growth of SD
      rat tenocytes. Using the technique of microcontact printing and microfluidic
      channels, we prepared micropatterned microgrooves with a 10 microm width and 4
      microm depth on silicone membrane substrates. The microgrooves were coated with
      CNI at concentrations 0.25, 0.5, 0.75, 1.0, and 1.25 mg/ml, respectively. The rat
      tenocytes at 1 x 10(5)/ml were seeded onto the CNI-coated substrates and the
      control substrates (without CNI coating), and then cultured in a humidified 37
      degrees C/5% CO2 incubator for 48 hours. Cell proliferation was measured by MTT
      method. After 1, 12, 24, 48 hrs of incubation, the tenocytes' alignment and
      morphology were observed by means of inverted phase microscope, scanning electron
      microscope and fluorescent microscope. The results showed there was obvious
      orientation of tenocytes in CNI-modified grooves, and most of the tenocytes
      spread along the grooves. The tenocyte orientation became more obvious with the
      increasing CNI concentration over a range from 0.25 to 1.25 mg/ml. This method
      could find important application in the construct of engineered tendons which
      need precise spatial organization of cells.

PMID- 18610629
TI  - [Study on active catheter for minimally invasive surgery based on large
      deflection theory].
AB  - A kind of active catheter used for minimally invasive surgery and actuated by
      shape memory alloy (SMA) was developed in this paper. The outer diameter of the
      catheter is 1.25 mm. The catheter was designed to consist of several bending
      units for achieving a large bending angle, but at the same time not increasing
      the outer diameter too much. It was considered that the deflection curve of axis
      of the catheter is determined by the output force of the SMA actuators. Based on
      large deflection theory, the deflection curve equation of the axis of the
      catheter was set up using precise form of the curvature. Through integral
      transform, the length and output force of each SMA actuator under the
      anticipative attitude of the tip of the active catheter were obtained, and the
      accurate coordinate of the center of the joint was givein. This study has
      provided great convenience to get control of the catheter, and has improved, to a
      certain extent, the design philosophy of problems such as active catheter.

PMID- 18610630
TI  - [A long term accelerating corrosion fatigue texting of coronary stents in vitro].
AB  - According to the related standards, an in vitro corrosion fatigue testing of
      coronary stents was designed. The stents were fixed in the latex tubes, which
      were full of 0.9% saline solution, and radial stress was produced for simulating
      natural vessel. The accelerated fatigue test was performed with 4 x 10(8) cycles
      at a frequency of 60 Hz, which was equal to 10 years in vivo implantation. Twelve
      coronary stents made from stainless steel were adopted in the experiment. The
      bulk structure and surface morphology before and after testing were analysed by
      scanning electron microscopy. The structure damage and surface change caused by
      corrosion fatigue were identified and the probable reasons were proposed.

PMID- 18610631
TI  - [Steep pulse changes the expression of tissue factor in ovarian tumor].
AB  - As a micro-wound and target-aimed technology without special limitation, Electric
      Pulses have been widely researched in tumor treatment and the effects have been
      demonstrated by a series of experiments, yet the mechanism has not been explained
      clearly. In this experiment, energy controllable steep pulse (ECSP) was used to
      treat nude mice bearing human ovarian tumor, and the result was compared with
      that of the control group. The expression of an important coagulant factor-tissue
      factor (TF) was analyzed, as TF was also a tumor indicator of invasion and
      metastasis, the result may indicate the relationship among ECSP, thrombosis and
      tumor invasion. In this study, to shed light on the mechanism of tumor treatment
      in electrical fields, nude mice bearing ovarian tumors were randomly divided into
      the treated group and the untreated group. We treated the former group and took
      out the tumor instantly. The thrombosis and necrosis of ovarian tumor were
      observed under microscope. The expression of TF was analyzed by SP
      immunohistochemistry and RT-PCR. Lower level of TF expression was noticed in the
      tumor tissue treated by ECSP, and more apparent thrombosis was also seen in this
      group. The results make it clear that ECSP can accelerate thrombosis and consume
      coagulant factors such as TF, and that low expression of TF in tumor tissue can
      cut out the signal paths of tumor invasion. So it is suggested that ECSP may
      restrain tumor invasion and metastasis by modulating thrombosis.

PMID- 18610632
TI  - [Effects of CTGF gene silencing on the proliferation and myofibroblast
      differentiation of human lung fibroblasts].
AB  - Connective tissue growth factor (CTGF) is involved in the differentiation of lung
      fibroblast into myofibroblast and is considered as an important mediator in the
      pathogenesis of pulmonary fibrosis. In the present study, a CTGF small
      interference RNA (siRNA) expressing plasmid (CTGF-siRNA) was constructed and
      stably transfected into human lung fibroblast cell line, MRC-5. Stable clones
      with CTGF gene silencing (CTGF-siRNA/MRC-5) were successfully established by G418
      screening and further confirmed by real-time quantitative PCR and Western blot.
      Cell proliferation was investigated by growth curve analysis, and cell doubling
      time of the CTGF-siRNA/MRC-5 cells was markedly longer than that of the control
      cells (P < 0.05). Compared with control cells, the expression of alpha-smooth
      muscle actin (alpha-SMA), the marker of myofibroblast differentiation, was
      decreased in CTGF-siRNA/MRC-5 cells. Moreover, the deposition of extracellular
      matrix (ECM) proteins (such as collagen type I and fibronectin) in CTGF-siRNA/MRC
      5 cells was also declined. Our data suggest that CTGF may play an important role
      in the differentiation of lung fibroblast into myofibroblast, and that siRNA
      targeting CTGF gene might provide a new strategy for gene therapy of pulmonary
      fibrosis.

PMID- 18610633
TI  - [Establishment of cDNA microarray technology and analysis of gene expression
      profiles in human esophageal cancer cell line ECa109].
AB  - To screen the genes associated with esophageal cancer, a cDNA microarray
      technique was established and used for the analysis of the gene expression
      profile in human esophageal cancer cell line ECa109. The results showed that 107
      (12.08%) genes differentially expressed among 886 target genes were identified
      between ECa109 cell line and normal human esophageal epithelial cells (HEEC), of
      which 51 (5.76%) were up-regulated and 56 (6.32%) down-regulated. Two genes were
      validated by quantitative RT-PCR (Q-RT-PCR) and the results were identical. The
      RNA amplification technique based-T7 RNA polymerase was established. The gene
      expression profile revealed better consistency between the amplified samples and
      those without amplification by T7 RNA polymerase, which provides a method for
      studying the profile of minute quantities of tumor cells in primary esophageal
      cancers. And the preliminary study on differential expression gene profile also
      enables us to have an understanding of the pathogenesis and pathomechanism of
      esophageal cancer.

PMID- 18610634
TI  - [Effect of antisense oligonucleotides targeting focal adhesion kinase on the
      proliferation and activation of hepatic stellate cells].
AB  - Hepatic stellate cell (HSC) plays a pivotal role in liver fibrosis and
      isconsidered as one of the therapeutic targets for the treatment of hepatic
      fibrosis. Focal adhesion kinase (FAK) has been shown to play an important role in
      the HSC activation. The aim of the study is to explore the role of FAK in the
      proliferation and activation in culture-activated rat HSCs by using a specific
      antisense oligonucleotides targeting FAK (FAK-ASON). Rat HSCs were prepared from
      SD rats by in situ perfusion of pronase and collagenase and single-step density
      Nycodenze gradient. Culture-activated HSCs were transfected with the FAK-ASON (1
      microM) by lipofectamine 2000 for 24, 48 or 72 hours. The proliferation of HSC
      was detected by MTT assay. The expression of the marker of HSC activation, alpha
      smooth muscle actin (alpha-SMA), was assessed by reverse transcription-
      polymerase chain reaction (RT-PCR) and Western blot. The inhibition rates for HSC
      proliferation 24, 48 and 72 hours after transfection were 65.5% +/- 5.8%, 46.8%
      +/- 4.3% and 35.7% +/- 5.2% respectively. Transfection of FAK-ASON could
      significantly inhibit the proliferation of HSC. Meanwhile, treatment with the FAK
      ASON could markedly decrease the mRNA and protein expression of alpha-SMA in rat
      HSC. The specific FAK-ASON may have an inhibitory effect on the proliferation and
      activation in rat HSC.

PMID- 18610635
TI  - [In vivo study on the potential differention capabilities of human peripheral
      blood-derived mononuclear cells transplanted into the nude mice with myocardial
      infarction].
AB  - The purpose of this study was to observe whether human peripheral dervied
      monouncleas cells (hMNCs) could participate in the regeneration process of the
      ischemic hearts in the way of differentiating into cardiomyocytes, vascular
      endothelial cells and smooth muscle cells. hMNCs were transplanted into the
      bodies of the mice with myocardial infarction through the tail vein injection.
      Hearts were harvested 2-12 weeks after injection then sliced up into frozen
      sections of 5 micron thickness. Double immunofluorescence staining was used to
      test the differentiation of the grafted cells into cardiomyocytes, smooth muscle
      cells and vascular endothelial cells which revealed that cells expressing both
      HLA and TNT, HLA and alpha-SMA, HLA and vWF existed in the hearts of the mice.
      According to the study, it is probable that hMNCs could participate in the
      regeneration process of the infarcted hearts in the way of differentiation.

PMID- 18610636
TI  - [Research on the development of image guided oral implant system].
AB  - In this paper is introduced an image guided oral implant system (IGOIS),
      including the 3D surface-model generation through Marching Cubes algorithm and
      large-scale triangular mesh simplification, the realization of pre-operative
      planning module with computer graphics and image processing technology, the non
      invasive point-to-point registration with the fabrication of tooth-supported
      polymer resin templates and ICP algorithm, and the development of the real-time
      navigation system software by programming in VTK and VC+ +6.0. The experimental
      test for a patient's rapid prototype model shows that with the support of IGOIS,
      the precision achieved in the planning phase can be transferred to the patient so
      that the accuracy of the oral implant surgery under difficult conditions is
      improved.

PMID- 18610637
TI  - [Study on the effect of spectral details encoding in speech processing on
      Mandarin recognition for cochlear implants users with speech maskers].
AB  - The modern multi-channel cochlear implant devices produce good speech recognition
      scores in quiet. However, the ability of most implant users to understand speech
      with the speech maskers remains quite poor. The goal of this study is to
      investigate the effect of spectral details encoding in speech processing on
      Mandarin recognition based on various acoustic models. The improvement of the
      strategies that encoded spectral details was observed for speech recognition with
      speech maskers. We also proposed the implementation methods to improve the
      strategy and stimulate further investigation.

PMID- 18610638
TI  - [Precise segmentation of cleavage of the neuron stem cells in time lapse image
      sequences].
AB  - To study the cleavage of neuron stem cells in time lapse image sequences and
      realize their features abstraction, identification and tracking, a precise
      segmentation algorithm that can preserve the shape of division cells is presented
      in this paper. The fuzzy threshold segmentation is based on Zadth's maximum
      entropy. The optimal parameters of the maximum fuzzy entropy are decided by
      genetic algorithm. Region merging and splitting of the under-segmentation objects
      of the result of fuzzy segmentation are realized by weighted distance transform,
      region labeling and some operations on morphology. By comparison with some
      results of fuzzy and hard segmentation, this algorithm can implement the precise
      segmentation that is necessary for some specified objects in automatic
      identification and tracking of neuron stem cells.

PMID- 18610639
TI  - [Control and realization of a novel bioartificial liver support system].
AB  - In this paper are introduced the design principle and its realization of a
      bioreactor's control for bioartificial liver support system. To meet the special
      requirement of circumstances in the culture and metabolism of hepatocytes, a
      control algorithm based on interactive control was designed and tested in the
      experiment to achieve sound performances. Some methods of control were used in
      the algorithm, such as PID (Proportional integral differential) algorithm,
      predictive control, and APC (Advanced process control). In the experiment, HepG2
      were cultured continuously for 60 hours under 37 degrees C +/- 0.2 degrees C
      (temperature), 95% +/- 10% (dissolved oxygen) and 7.3 +/- 0.2 (pH value). The
      samples were collected at 24 h and 60 h. After morphological studies, it was
      found that the growth of the cells was obviously better than that of the control
      group. In conclusion, most of the parameters in the process of hepatocyte culture
      were exactly controlled. The growth of hepatocytes was quite well in the
      bioreactor. These data might contribute to further researches on bioartificial
      liver support system.

PMID- 18610640
TI  - [The fabrication of hepatitis B electrochemical immunosensor array].
AB  - Based on integrate circuit (IC) technology, an eight-channel gold electrodes
      (GEs) array was developed. The immunosensor array is prepared by co-immobilizing
      thionine and Hepatitis B (HB) antibody on the gold electrodes through covalently
      binding them to GEs with a cysteamine/glutaraldehyde linkage. Hepatitis B surface
      antigen (HBsAg) was detected qualitatively and quantitatively by the peak current
      decrease percentage of the thionine. HBsAg positive/negative standard serum was
      well defined by the array. 8-channel synchronous detection for HBsAg was noted to
      be of good accuracy and reliability. The results of its clinical application were
      in good agreement with the results from ELISA.

PMID- 18610641
TI  - [Synthesis and application of novel dental adhesive materials of 10
      methacryloyloxydecyl dihydrogen phosphate].
AB  - 10-methacryloyloxydecyl dihydrogen phosphate was synthesized from the reaction of
      phosphoryl chloride with methylacrylic acid and 1, 10-decanediol. The structure
      of product was characterized by 1H-NMR, 31P-NMR and MS. The effect of this
      product on the bond durability of composite resin joined to enamel, dentin and
      dental alloy was evaluated by the test of shear strengths. 10
      methacryloyloxydecyl dihydrogen phosphate significantly elevated the bond
      strength of the composite resin joined to enamel, dentin, Ti alloy and Co-Cr
      alloy; the relevant shear strengths were 13.5, 11.2, 16.2 and 18.1 MPa,
      respectively.

PMID- 18610642
TI  - [A novel mechanical orientation system used for body precise radiotherapy].
AB  - In the end of last century, there was a leap in the technological quality of
      radiotherapy, which is incarnated in three new technologies: Stereotactic
      radiation surgery (SRS), three-dimensional conformal radiation therapy (3D-CRT)
      and intensity modulated radiation therapy (IMRT). However, the achievement of
      these technologies has a close relationship with the precise orientation of
      tumour. Especially, in terms of body stereotactic precise radiation therapy, its
      body mechanical orientation system is the kernel to guarantee the accuracy of
      radiotherapy. This paper presents a novel mechanical orientation system for body
      precise radiotherapy. It is characterized by flexible adjustment, deft removal,
      easy disassembly and accurate orientation using apart structure to substitute old
      integer structure and adopting single segment Z shape orientation marker staff.
      The new mechanical orientation system guarantees the effect of tumour
      radiotherapy, which is worthy to be recommended for clinical use.

PMID- 18610643
TI  - [Removal of artifacts from EEG signal].
AB  - As a kind of physiological signals, the electroencephalogram (EEG) represents the
      electrical activity of the brain. Because of its higher time-varying sensitivity,
      EEG is susceptible to many artifacts, such as eye-movements, blinks, cardiac
      signals, muscle noise. These noises in recording EEG pose a major embarrassment
      for EEG interpretation and disposal. A number of methods have been proposed to
      overcome this problem, ranging from the rejection of various artifacts to the
      effect estimate of removing artifacts. This paper reviews many kinds of methods
      for artifact rejection in the EEC recently, including regression-based methods,
      artifact subtraction, principal component analysis (PCA), independent component
      analysis (ICA) and wavelet transform. The specific assumptions of each method and
      its advantage/disadvantage are also summarized.

PMID- 18610644
TI  - [A review of electrical impedance tomography based on MRI technique].
AB  - In this paper, a review of a new electrical impedance tomography technique
      magnetic resonance electrical impedance tomography (MREIT) is presented. Some
      medical imaging methods are briefly introduced. The basic theory of MREIT is
      given as well as its realization methods and developing status. The merits and
      challenges of this new trend are also demonstrated.

PMID- 18610645
TI  - [Characterization and applications of self-assembled lipid films: atomic force
      microscopy studies].
AB  - Self-assembled lipid films provide new insights into the structure-function
      relationships of biomolecules at the molecular level. It has potential
      applications in biology and bionics. In this paper, with regard to atomic force
      microscopy (AFM) characterization, the surface structures and growth kinetics of
      self-assembled lipid films as well as their applications in high-resolution AFM
      imaging of surface-immobilized biomolecules such as proteins, DNA and enzymes are
      reviewed.

PMID- 18610646
TI  - [Application of endothelial progenitor cells in vascular tissue engineering].
AB  - Endothelial progenitor cells (EPCs) are immature endothelial cells which have the
      capacity to proliferate, migrate and differentiate into mature endothelial cells
      from bone marrow to the peripheral circulation. EPCs have been shown to
      participate in postnatal endothelial repair and neovascularization of ischemic
      organs, and have been used as a new source of seeded cells in vascular tissue
      engineering. In this review, we focus on the origin, identification, property and
      function of EPCs as well as their application in vascular tissue engineering.

PMID- 18610647
TI  - [Research and development of artificial retina material].
AB  - The application of artificial retina was introduced. The principal
      characteristics of artificial retina material were reviewed in particular.
      Moreover, the recent research development and application prospect were
      discussed.

PMID- 18610648
TI  - [Application of gene therapy in tumor adoptive immunotherapy].
AB  - Adoptive cell transfer of tumor-infiltrating lymphocyte (TIL) has resulted in
      clear and reproducible responses in a substantial percentage (approximately 50%)
      of patients with metastatic melanoma. The availability of tumor reactive TIL
      limits the use of adoptive cell transfer for the treatment of most non-melanoma
      cancer patients. Recent report indicated that adoptive transfer of T lymphocytes
      genetically modified with T-cell receptor (TCR) against a tumor antigen resulted
      in objective response in melanoma patients, thus shedding light on the use of
      this strategy for the treatment of common epithelial cancers beyond melanoma. In
      this review, the current status and potential use of genetic modification in the
      adoptive immunotherapy of cancer patients are be discussed.

PMID- 18610649
TI  - [Advances in interaction of macrophages with tissue engineering related
      biomaterials].
AB  - The host inflammatory reaction is a normal response to injury and the presence of
      foreign substances. Macrophage is one of the principal cell types in controlling
      host inflammatory and immune processes; hence, its response to biomaterials has a
      direct impact on biocompatibility and stability of biomaterials in vivo. This
      review describes the interaction of macrophages with tissue engineering related
      biomaterials. The bulk physicochemical structure and surface performance of
      biomaterials could be designed to control macrophages behaviors (i. e. adhesion,
      activation, fusion, apoptosis) and host responses, resulting in improving
      biocompatibility of biomaterials.

PMID- 18610650
TI  - New approaches for Helicobacter vaccine development--difficulties and progress.
AB  - Despite the enormous progress in understanding the process of bacterial
      pathogenesis and interactions of pathogens with eucaryotic cells the infectious
      diseases still remain the main cause of human premature deaths. It is now
      recognized that Helicobacter pylori infects about half of the world's population.
      Based on results of clinical studies the World Health Organization has assigned
      H. pylori as a class I carcinogen. The review presents new achievements aimed at
      construction efficient and safe anti-Helicobacter vaccine. We discuss the new
      global technologies such as immunoproteomics employed for selecting new
      candidates for vaccine construction as well as new vaccine delivery systems. The
      review presents also our knowledge concerning H. pylori interaction with immune
      system which might facilitate modulation of the host immune system by specific
      adjuvant included into vaccine.

PMID- 18610651
TI  - Amplification of a single-locus variable-number direct repeats with restriction
      fragment length polymorphism (DR-PCR/RFLP) for genetic typing of Acinetobacter
      baumannii strains.
AB  - In search of an effective DNA typing technique for Acinetobacter baumannii
      strains for hospital epidemiology use, the performance and convenience of a new
      target sequence was evaluated. Using known genomic sequences of Acinetobacter
      baumannii strains AR 319754 and ATCC 17978, we developed single-locus variable
      number direct-repeat analysis using polymerase chain reaction-restriction
      fragment length polymorphism (DR-PCR/RFLP) method. A total of 90 Acinetobacter
      baumannii strains isolated from patients of the Clinical Hospital in Bydgoszcz,
      Poland, were examined. Initially, all strains were typed using macrorestriction
      analysis of the chromosomal DNA by pulsed-field gel electrophoresis (REA-PFGE).
      Digestion of the chromosomal DNA with the ApaI endonuclease and separation of the
      fragments by PFGE revealed 21 unique types. Application of DR-PCR/RFLP resulted
      in recognition of 12 clusters. The results showed that the DR-PCR/RFLP method is
      less discriminatory than REA-PFGE, however, the novel genotyping method can be
      used as an alternative technique for generating DNA profiles in epidemiological
      studies of intra-species genetic relatedness of Acinetobacter baumannii strains.

PMID- 18610652
TI  - Regulation of Yersinia enterocolitica mal genes by MalT and Mlc proteins.
AB  - To show the role of MalT protein in the regulation of mal genes, encoding
      proteins involved in transport and metabolism of maltose/ maltodextrins in
      Yersinia enterocolitica, we constructed a malT mutant which was characterized by
      a strong reduction in maltose transport and a loss of MBP protein. We also
      studied the influence of MalT activity on the production of Yop proteins in Y.
      enterocolitica and found that the level of these virulence factors is not changed
      in the malT mutant. Subsequently, transcriptional fusion malT::lacZYA was applied
      to study the activity of malT promoter. Monitoring of beta-galactosidase activity
      suggests the influence of catabolic repression on malT transcription, sincethe
      activity of malT promoter was decreased twofold in the presence of glucose.
      Furthermore, Mlc protein was identified in Y. enterocolitica as a factor
      regulating the transcription of malT. We observed a two-fold increase in the
      level of malT transcription in the mlc mutant background. Moreover,
      overproduction of Mlc protein strongly inhibited the activity of malT promoter.
      Thus, the data presented in this study suggest that the level of mal gene
      expression in Y. enterocolitica may be regulated by two proteins: MalT, the
      activator of mal transcription and Mlc, the repressor of malT expression.

PMID- 18610653
TI  - Proteolytic activity of clinical Candida albicans isolates in relation to
      genotype and strain source.
AB  - Proteolytic activity is regarded as one of the most important virulence factors
      of Candida albicans. Several authors recently demonstrated that some karyotypes
      and genotypes harbouring a group I self-splicing intron (CaLSU) located in the
      gene encoding the large rRNA subunit showed a high level of proteinase
      production. The aim of this study was to investigate the correlation between the
      level of proteinase production and the presence of the CaLSU intron in C.
      albicans isolates originating from the blood and respiratory tracts
      (sputum/pharyngeal swabs) of patients with and without oropharyngeal candidosis.
      The results revealed statistically significant differences in genotype
      distribution and the level of proteinase production between the C. albicans
      isolates obtained from blood and from the respiratory tract. Genotype A, without
      the intron, was prevalent in all groups of strains and its prevalence was higher
      among isolates from blood (75%) and from patients with candidosis (80%) compared
      with strains from colonisation (as opposed to infection) (57.8%). Isolates from
      blood produced significantly less proteinase than isolates from the respiratory
      tract (p<0.02), and this difference should be attributed to lower proteinase
      production of genotypes B and C from blood compared with genotypes B and C from
      the respiratory tract (p<0.01). The higher proteinase production of genotype B
      than of genotype A was found among respiratory tract isolates only. The presented
      data indicate that the association between proteinase production and the CaLSU
      intron depends on the strains' population. Further study is needed on well
      defined groups of clinical isolates to elucidate whether the observed diversity
      in proteinase production plays a role in the selection of strains inducing
      bloodstream infections.

PMID- 18610654
TI  - Study on bioactive compounds from Streptomyces sp. ANU 6277.
AB  - An attempt was made to study the bioactive compounds from a terrestrial
      Streptomyces sp. ANU 6277 isolated from laterite soil. Four active fractions were
      recovered from the solvent extracts obtained from the culture broth of five day
      old strain. Three bioactive compounds were purified and identified as 3
      phenylpropionic acid, anthracene-9,10-quinone and 8-hydroxyquinoline. The
      components of the partially purified fourth active fraction were analyzed by gas
      chromatography-mass spectrometry and identified as benzyl alcohol, phenylethyl
      alcohol and 2H-1, 4-benzoxazin-3 (4H)-one. Four active fractions were screened
      for antimicrobial activity against Gram-positive and Gram-negative bacteria, and
      fungi including phytopathogenic, toxigenic and dermatophytic genera. Among these
      metabolites, 8-hydroxyquinoline exhibited strong antibacterial and antifungal
      activity as compared to 3-phenylpropionic acid and anthracene-9,10-quinone.

PMID- 18610655
TI  - Clinical presentation of extraintestinal infections caused by non-typhoid
      Salmonella serotypes among patients at the University Hospital in Cracow during
      an 7-year period.
AB  - The most characteristic finding in non-typhoid salmonella (NTS) infection is
      acute food related outbreaks of gastroenteritis, which is usually benign and self
      limiting. However, more serious extraintestinal findings, such as bacteraemia and
      focal infections localized to any organ may appear. The objective of this paper
      is to describe the most important characteristic of the extraintestinal
      infections due to NTS serotypes observed in University Hospital, in Cracow
      between January 2000 and December 2006. To do so, we reviewed the clinical
      presentations, risk groups, complications and outcomes of in-patients, in which
      extraintestinal non-typhoid Salmonella serotypes were isolated, applying a
      clinomicrobiological protocol. Out of 30 patients with either bacteraemias (n =
      22) or focal salmonella infections (n = 8), 12 had malignancies, 17 had immune
      dysfunction state, 9 had gastrointestinal disorders and 8 had chronic heart,
      pulmonary or kidney disease. Four of these patients (13%) who had hematological
      malignancies (2), renal transplantation (1) and pulmonary disease (1) died.
      Regarding the clinical picture, primary bacteraemia and focal infections occurred
      with similar frequency (33.3% and 26.7%, respectively); the remaining were
      bacteraemias secondary to gastroenteritis. The incidence rate (mean 0.30/1000
      hospital admission/year) increased steadily from 0.19/1000 to 0.32/1000 hospital
      admission during the study period. From 30 Salmonella isolates from
      extraintestinal samples collected, only four isolates were resistant to
      ampicillin, ciprofloxacin or trimethoprim-sulfamethoxazole. This finding indicate
      that multidrug resistance does not represent a serious problem among NTS
      serotypes collected from the our medical center as monitored over a period of 7
      years. Given this presentation, clinicians need to have a high index of suspicion
      and to consider preemptive therapy, especially in elderly patients who are likely
      to develop severe immunosuppression following interventions.

PMID- 18610656
TI  - Statistical optimization of alpha-amylase production by Streptomyces erumpens
      MTCC 7317 cells in calcium alginate beads using response surface methodology.
AB  - Alpha-amylase has a wide range of applications in starch industries, i.e. baking,
      brewing, distillery, etc. The alpha-amylase production from Streptomyces erumpens
      MTCC 7317 immobilized cells was compared with that of free cells. The immobilized
      cells of S. erumpens in calcium alginate beads were more effective for production
      of alpha-amylase (12.2% more yield) than free cells. Response surface methodology
      (RSM) was used to evaluate the effect of main variables, i.e. incubation period,
      pH and temperature on enzyme production with immobilized cells. A full factorial
      Central Composite Design (CCD) was applied to study these main factors that
      affected alpha-amylase production. The experimental results showed that the
      optimum incubation period, pH and temperature were 36 h, 6.0 and 50 degrees C,
      respectively for immobilized cells. Repeated batch fermentation of immobilized
      cells in shake flasks carried out in starch-beef extract medium showed that S.
      erumpens cells were physiologically active on the support even after four cycles
      of fermentation.

PMID- 18610657
TI  - The influence of soluble microbial products on microbial community composition:
      hypothesis of microbial community succession.
AB  - Soluble microbial products (SMP) are organic compounds produced by activated
      sludge microorganisms as they degrade substrates. They include by-products of
      microbial activity, death and lysis. The available literature does not reveal how
      SMP influence microbial community composition. In this regard, we microscopically
      studied changes in composition of microbial communities, especially protozoa and
      metazoa, under the influence of increased as well as reduced levels of SMP. The
      presence of SMP at high level significantly caused changes in microbial community
      composition. Microbial species shifted from attached ciliates (12-175 microm) to
      free-swimming and crawling ciliates (35-330 microm) and then invertebrates, which
      included rotifers (0.2-1 mm) and nematodes (1-50 mm). The shift of small-size
      microorganisms to large ones was observed as one of the most significant
      influences of SMP. Attached ciliates reappeared when we removed the SMP that had
      accumulated in the bioreactors - we have called this as the resurrection
      phenomenon of microorganisms. Such rapid changes in microbial community
      composition were not observed in the experiment with low concentration of SMP.
      Overall, the results suggest that accumulation of SMP is one of the intrinsic
      regulatory mechanisms that control viability and dormancy of microbial
      communities in activated sludge.

PMID- 18610658
TI  - Established and abandoned tea (Camillia sinensis L.) rhizosphere: dominant
      bacteria and their antagonism.
AB  - Some parts of the Indian Himalayan region are covered by established and
      abandoned tea bushes. Rhizospheric soils of these plants were studied for
      bacterial dominance and antagonism. Representatives of Bacillus and Pseudomonas
      genera were found to dominate the rhizosphere of established and abandoned tea
      bushes, respectively. Amongst the isolated species Bacillus subtilis and Bacillus
      mycoides appeared to be closely associated with roots of established tea bushes
      while the rhizosphere of abandoned tea bushes was dominated by Pseudomonas
      putida. Four isolates of both B. subtilis and P. putida were selected on the
      basis of maximum antibacterial activity. The bacteriocin-like activity of B.
      subtilis and P putida strains was detected to be active over a range of
      temperature 0-50 degrees C and was sensitive to proteolytic enzymes. Incubation
      of indicator strains with different concentrations of bacteriocin-like substances
      confirmed their bactericidal activity. Various species of Bacillus and
      Pseudomonas behaved antagonistically amongst themselves due to the production of
      bacteriocins under in vitro conditions.

PMID- 18610659
TI  - Polymorphism in the ITS region of ribosomal DNA of Cochliobolus sativus isolates
      differing in xylanase production.
AB  - The restriction of PCR-amplified internal transcribed spacers (ITS) ofribosomal
      DNA was used to confirm the genetic variation among 22 isolates of Cochliobolus
      sativus differing in their xylanase production. Results show a high level of
      diversity of ITS-RFLP markers among the isolates. The molecular parameter used
      showed that C. sativus isolates reside in three phylogenetic groups. There was
      observed the resolution between clustering of isolates and their xylanase
      production level.

PMID- 18610661
TI  - Spirometry: pitfalls and interpretation.

PMID- 18610660
TI  - Usefulness of strb1 and 16S rDNA-targeted PCR for detection of Streptomyces spp.
      in environmental samples.
AB  - In this study, we revealed rapid detection of streptomycin-producing Streptomyces
      spp. by extraction of total soil DNA from 14 soil samples using a modified lysis
      method followed by PCR amplification ofa genus-specific sequence in the
      Streptomyces' 16S rDNA gene. DNA band of the expected size (438 bp) was seen with
      all the samples. Additionally, specific amplification of the streptomycin-coding
      gene (strb1) directly from soil revealed the presence of a single DNA band of 940
      bp. These results indicate that PCR-amplification of Streptomyces specific genes
      could be used for direct detection of streptomycin-producing Streptomyces species
      from soil.

PMID- 18610663
TI  - Advantages of late expiratory relaxation during maximal forced expiratory
      maneuver.
AB  - A modification of the maneuver for the maximal expiratory flow volume (MEFV)
      curve was described recently to improve the rate of achieving the acceptability
      criteria of the American Thoracic Society. The maneuver allows the subject to
      relax in the later part of expiration. The present study was carried out to
      determine if the modified spirometry technique offered any advantages over the
      standard FVC maneuver in asthma patients with a wide range of airways
      obstruction. MEFV curves were obtained in seventy-two subjects with standard and
      modified procedures in a randomized, crossover design. The patients were divided
      into four groups depending on the degree of airways obstruction-normal
      spirometry, mild, moderate and severe airways obstruction. The spirometric
      parameters (FVC, FEV1, FEV/FVC ratio, FET, PEFR and F25-75) were compared in each
      group. The modified technique gave a higher FVC measurement especially in
      patients with moderate and severe airways obstruction along with increased FET.
      PEFR and FEV1 were not different between the techniques. FEV1/FVC ratio was
      significantly decreased in patients with moderate and severe airways obstruction.
      Both the techniques gave equally acceptable and reproducible results with similar
      variability for FEV1 and FVC. It was concluded that the modification of the
      standard FVC maneuver by allowing the subject to relax in the later part of
      expiration is advantageous as it yields a lower FEV1/FVC ratio without affecting
      the FEV1, has the same within-session variability and is less strenuous.

PMID- 18610662
TI  - Wegener's granulomatosis in India: clinical features, treatment and outcome of
      twenty-five patients.
AB  - OBJECTIVE: To report our clinical experience on Wegener's granulomatosis (WG).
      METHODS: A retrospective review of case records of all patients with WG in our
      Rheumatology Clinic during the period July 1988 to June 2000 was carried out and
      the details of demography, clinical and laboratory data, treatment and outcome
      were obtained and analysed. RESULTS: Twenty-five patients (16 females and 9
      males) were found eligible for inclusion in the study. The mean age and duration
      of symptoms at presentation were 33.5 years and 5.5 months, respectively. Two
      patients had limited WG. Twenty-two patients with generalized WG were treated
      with standard regimen comprising oral prednisolone (1 mg/kg/day) and oral
      cyclophosphamide (2 mg/kg/day). Cyclophosphamide was continued for at least one
      year after the patient attained remission. One patient was treated with
      intravenous cyclophosphamide regimen. The two patients with limited WG were
      treated with oral prednisolone and methotrexate (10-12.5 mg as a single dose per
      week). Remission was achieved in 24 patients after a median time of six months.
      The median follow-up of patients was five years (range 4 months-11 years). Five
      patients were lost to follow-up. Eight patients suffered a relapse. The mean time
      for relapse was 34 months after the initial remission. Seven out of eight
      patients remitted again after reinstitution of the initial induction regimen. One
      patient died of diffuse pulmonary haemorrhage despite early institution of
      therapy. CONCLUSION: WG is being increasingly diagnosed in India now because of
      greater awareness and diagnostic aids. Although remissions are easy to achieve,
      relapses continue to pose a challenge to the treating physician.

PMID- 18610664
TI  - Decline in beta-2 microglobulin levels after antitubercular therapy in tubercular
      patients with HIV infection.
AB  - BACKGROUND: Infection with Mycobacterium tuberculosis results in a state of
      immune activation, more so, when there is concomitant HIV infection. Beta-2
      microglobulin (B2M) is a useful marker to study the state of immune activation
      among the HIV infected. Objective. To study the modulation of B2M levels among
      patients with HIV/TB coinfection, to correlate it with the CD4 count and also to
      study the change in these levels after four weeks of therapy. MATERIAL AND
      METHODS: Twelve patients with HIV infection and having concomitant TB diagnosed
      on the basis of positive acid fast bacilli were studied both at baseline and then
      at four weeks. Fourteen HIV infected individuals who had no overt opportunistic
      infection at the time of the study were also studied along with fourteen age and
      sex matched healthy volunteers. CD4 counts were performed using a flowcytometer.
      B2M was measured using a commercially available ELISA kit. RESULTS: B2M levels in
      HIV/TB coinfected patients were 1.62+/-0.45 mg/L (range 1-2.7 mg/L) and were
      significantly higher (p<0.0002) when compared with healthy controls, whose levels
      were 0.74+/-0.05 mg/L (range 0.48-81 mg/L). The levels in HIV infected
      individuals free of opportunistic infections were 1.2+/-0.16 mg/L (range 0.78
      1.92 mg/L) and were significantly lower than the levels in HIV/TB coinfected
      (p<0.017), but significantly higher than the levels in healthy controls (p<0.01).
      Four weeks of antitubercular therapy resulted in a decline in B2M to 1.08+/-0.26
      mg/L (range 0.8-1.74 mg/L) and was statistically significant (p<0.012). There was
      no correlation between the CD4 counts and the pre-treatment levels of B2M among
      these patients. CONCLUSION: Patients with HIV/TB coinfection had significantly
      higher levels of B2M than individuals with HIV infection without associated
      opportunistic infection and healthy controls. Four weeks of anti-tuberculous
      therapy resulted in a significant decline in these levels.

PMID- 18610665
TI  - Nasobronchial allergy or allergic rhinobronchitis; the unified concept: a review
      with a special reference to India.
AB  - The close and constant association of allergic rhinitis (AR) and asthma, both in
      children and adults, is hardly mentioned in medical textbooks. Proper treatment
      is delayed, as these patients are often seen in rotation by chest physicians,
      allergy experts, otolaryngologists, general physicians and paediatricians. Even
      then treatment is directed mainly towards asthma with little attention being paid
      to associated rhinitis, often lying unrecognised in adults. The clinical pattern
      of asthma in children and adults differs in our country. Unless AR is treated
      simultaneously with asthma, recurrent AR will result likely in suboptimal control
      of asthma. Proof and arguement is brougnt forward to recognise the unified
      concept of nasobronchial allergy or rhinobronchitis for proper management.

PMID- 18610666
TI  - Pulmonary tuberculosis presenting with cannon-ball opacities.

PMID- 18610667
TI  - Bochdalek hernia in adulthood: an unusual presentation and diagnostic dilemma.
AB  - Bochdalek diaphragmatic hernia is one of the most important surgically
      correctable causes of respiratory distress in the newborn. Delayed presentation
      in adult life is uncommon. We present a case of a 46-year-old, multigravida
      Kashmiri woman, who was misdiagnosed earlier and treated for pulmonary
      tuberculosis. Diagnosis was established pre-operatively by plain chest radiograph
      and barium meal. A dorso-lateral defect was located on left side of diaphragm
      which was corrected by using a prolene mesh.

PMID- 18610668
TI  - Inflammatory pseudotumour of the lung : report of a case and review of
      literature.
AB  - A case of unusual benign tumour of the lung is described. The patient presented
      with a history of prolonged cough with expectoration, and fever with generalised
      weakness of shorter duration. Radiological examination of the chest revealed a
      large non-homogeneous opacity with calcification in the left lower zone. Fine
      needle aspiration cytology (FNAC) was inconclusive. Therefore, surgical
      exploration and a left lower lobectomy was performed. The diagnosis of
      inflammatory pseudotumour was made on histopathological examination.

PMID- 18610669
TI  - Cutis laxa and pulmonary emphysema.
AB  - Cutis laxa is a disorder of skin due to a defective elastin synthesis.
      Association with pulmonary emphysema has been described earlier and has always
      been reported to occur in childhood. A case of a 38-year-old female patient
      suffering from cutis laxa is reported who developed symptomatic pulmonary
      emphysema in adulthood.

PMID- 18610670
TI  - Echinococcosis: presenting as palpable lumps of breast.
AB  - While hydatid disease is common in developing countries, yet occurrence of
      echinococcal cysts in breast are rare. Our experience encountered in two patients
      with hydatidosis diagnosed on fine needle aspiration (FNA) is presented because
      it may cause a clinical dilemma with other cystic lesions of breast. No
      complications were observed after FNA in both the cases. The helpful role of
      indirect haemagglutination (IHA) test in evaluation of the disease is
      highlighted.

PMID- 18610671
TI  - Nebulized salbutamol-induced ocular manifestations.

PMID- 18610672
TI  - The archetype of laboratory diagnosis in tuberculosis: the shape of things to
      come.

PMID- 18610674
TI  - Inflammatory cytokine levels in induced sputum and bronchoalveolar lavage fluid
      in pulmonary sarcoidosis.
AB  - BACKGROUND: The immune inflammatory process in patients with sarcoidosis is not
      only compartmentalized within the alveolar walls, but also involves the bronchial
      airways. Analysis of induced sputum has been used as a non-invasive tool for
      investigating the airways and may reflect the endobronchial and parenchymal
      inflammation in patients with sarcoidosis. This present study was designed to
      measure the soluble pro-inflammatory cytokine levels interleukin-1 (IL-1),
      interleukin-6 (IL-6), tumuor necrosis factor-alpha (TNF-alpha) and percentage of
      macrophages expressing these cytokines in induced sputum and bronchoalveolar
      lavage (BAL) fluid in patients with pulmonary sarcoidosis. METHODS: Sputum
      induction and BAL was carried out in 27 patients with newly diagnosed
      sarcoidosis. Control group consisted of six patients with a normal chest
      radiograph (three patients with carcinoma esophagus and three patients with
      doubtful history of hemoptysis). Induced sputum was also obtained from 10 non
      smoking, non-atopic healthy controls. RESULTS: Percentage of macrophages
      expressing pro-inflammatory cytokines and soluble cytokine levels in induced
      sputum were higher in patients with sarcoidosis compared to both groups of
      controls. There was good correlation between IL-6 and TNF-alpha levels (r = 0.49,
      0.58 p < 0.05) and percentage of macrophages expressing all three cytokines (r =
      0.56-0.71, p < 0.01) between induced sputum and BAL fluid. Mild positive
      correlation between cytokine levels in sputum and age was also noted (r = 0.33
      0.38, p < 0.05). CONCLUSIONS: Induced sputum may reflect changes in cytokine
      milieu in BAL in sarcoidosis.

PMID- 18610673
TI  - Alginate nanoparticles as antituberculosis drug carriers: formulation
      development, pharmacokinetics and therapeutic potential.
AB  - BACKGROUND: Reduction in the dosing frequency of antituberculosis drugs (ATDs) by
      applying drug delivery technology has the potential to improve the patient
      compliance in tuberculosis (TB). Alginate (a natural polymer) based
      nanoparticulate delivery system was developed for frontline ATDs (rifampicin,
      isoniazid, pyrazinamide and ethambutol). METHODS: Alginate nanoparticles were
      prepared by the controlled cation induced gelification method and administered
      orally to mice. The drug levels were analysed by high performance liquid
      chromatography (HPLC) in plasma/tissues. The therapeutic efficacy was evaluated
      in M. tuberculosis H37Rv infected mice. RESULTS: High drug encapsulation
      efficiency was achieved in alginate nanoparticles, ranging from 70%-90%. A single
      oral dose resulted in therapeutic drug concentrations in the plasma for 7-11 days
      and in the organs (lungs, liver and spleen) for 15 days. In comparison to free
      drugs (which were cleared from plasma/organs within 12-24 h), there was a
      significant enhancement in the relative bioavailability of encapsulated drugs. In
      TB-infected mice three oral doses of the formulation spaced 15 days apart
      resulted in complete bacterial clearance from the organs, compared to 45
      conventional doses of orally administered free drugs. CONCLUSIONS: Alginate
      nanoparticles appear to have the potential for intermittent therapy of TB.

PMID- 18610675
TI  - Efficacy and safety of kanamycin, ethionamide, PAS and cycloserine in multidrug
      resistant pulmonary tuberculosis patients.
AB  - BACKGROUND: We carried out this study to determine the efficacy and safety of a
      regimen containing kanamycin, ethionamide, isoniazid, para-aminosalicylic acid
      (PAS) and cycloserine in the treatment of multidrug-resistant tuberculosis (MDR
      TB). METHODS: A prospective, uncontrolled study of 39 pulmonary tuberculosis
      patients, who had received adequate first-line antituberculosis treatment
      including supervised category II retreatment regimen, and were still sputum smear
      positive for acid-fast bacilli (AFB) in whom sputum culture revealed isolates of
      M. tuberculosis resistant to rifampicin and isoniazid with and without resistance
      to other antituberculosis drugs. They received kanamycin (initial 4-6 months),
      ethionamide, isoniazid, PAS and cycloserine for a minimum period of two years.
      RESULTS: Out of 39 patients, 29 (74.3%) achieved sputum conversion within six
      months and remained so at the end of two years. Two (5.1%) patients died, six
      (20.6%) patients were lost to follow up, and two (5.1%) patients remained sputum
      smear-positive for AFB through out the period of study. Twenty-nine patients,
      declared cured, were followed for an average period of 16 months (3-48 months),
      during which two (6.9%) patients relapsed, four (13.8%) patients were lost to
      follow-up and remaining 23 remained sputum smear-negative. Eight (21.1%) patients
      developed major side effects which required stoppage/change of drugs. CONCLUSION:
      In MDR-TB patients, regimen consisting of ethionamide, isoniazid, PAS and
      cycloserine and kanamycin appears to be effective and safe.

PMID- 18610676
TI  - Profile of lung cancer in Kashmir, India: a five-year study.
AB  - AIM: To study the clinico-pathological aspects of lung cancer, and the outcome of
      various treatment modalities. METHODS: A retrospective review of
      histopathologically confirmed lung cancer patients who were registered and
      treated at our institution over a period of five years was carried out. RESULTS:
      A total of 321 patients were studied. There was a preponderance of males (91.9%)
      as compared to females (8.1%). Smoking history was present in 88% of the male
      patients. Cough was the main presenting feature in 71.6% of patients. Diagnosis
      was established by bronchoscopy in 94% of cases. Squamous cell carcinoma was
      observed in 77.3%, while 17.1% had small cell carcinoma. Radiotherapy formed the
      main treatment modality alone (22.4%) and in combination (27%). Out of the 321
      patients, 206 were evaluable on follow-up. Local failure and distant metastasis
      were seen in 9.2% and 19.9% of cases, respectively. The overall survival rate of
      2, 3 and 5 years was 19.9%, 13.59% and 6.79%, respectively. CONCLUSIONS: . The
      outcome of lung cancer is poor. Increased survival is possible if the disease is
      detected early, treated adequately with multi modality approach.

PMID- 18610677
TI  - Treatment options of spontaneous pneumothorax.
AB  - Penumothorax is a benign condition with high morbidity and high recurrence rate;
      and remains a significant clinical problem worldwide. The exact underlying
      pathogenesis is probably multifocal and is still unclear. The initial approach to
      the management of spontaneous pneumothorax differs from country to country and it
      is very difficult to establish an international standard protocol. Needless to
      say, that the safest and most cost-effective treatment protocol for a particular
      center should be used. However, first episode of primary spontaneous pneumothorax
      can be managed conservatively and there is no consensus on optimal treatment of
      patients presenting with spontaneous pneumothorax specially those with first
      event. On the contrary, there is some consensus that some treatment is mandatory
      with second or recurrent spontaneous pneumothorax. Regardless of the chosen
      therapeutic modality, the treatment goals of spontaneous pneumothorax consist of
      elimination of the pleural air and also prevention of future recurrence.
      Therapeutic options include bed rest, oxygen supplementation, manual aspiration,
      chest tube drainage, thoracoscopic and surgical interventions. Till present,
      there are no prospective, randomised comparative studies between various
      treatment strategies but only few between various therapeutic techniques are
      available.

PMID- 18610678
TI  - Bilateral spontaneous pneumothorax in silicosis.
AB  - Occurrence of pneumothorax in silicosis is rare and when it occurs, pneumothorax
      is usually unilateral. We report here a patient with accelerated silicosis who
      presented with bilateral spontaneous pneumothoraces occurring simultaneously. The
      rarity of its clinical presentation in the form of bilateral simultaneous
      spontaneous pneumothorax combined with the typical clinical and radiological
      features of accelerated silicosis with tuberculosis make us to report this case.

PMID- 18610679
TI  - INH induced status epilepticus: response to pyridoxine.
AB  - Isoniazid is an effective and widely used drug in tuberculosis treatment. The
      administration of toxic amounts of INH causes recurrent seizures, profound
      metabolic acidosis, coma and even death but therapeutic dose of isoniazid is a
      very rare cause of seizures. We present a case of 44-year-old HIV positive
      African-American female who was recently started on a preventive dose of INH
      after being found purified protein derivative (PPD) positive. She developed
      status-epilepticus that did not respond to most of the antiepileptics. As soon as
      she received intravenous pyridoxine, the seizures terminated abruptly.

PMID- 18610680
TI  - Interlobar hydropneumothorax.
AB  - We report a case of interlobar hydropneumothorax in a 42-year-old male with
      chronic obstructive pulmonary disease and a history of tuberculosis in the past.
      The diagnosis was suspected from chest roentgenograms that showed an incompletely
      circumscribed air containing space with a fluid level. The diagnosis was
      confirmed by computed tomography. This unusual presentation of hydropneumothorax
      with striking radiological features prompted us to report this case.

PMID- 18610681
TI  - Tubercular oesophagocutaneous fistula.
AB  - A case of oesophageal tuberculosis complicated by an oesophagocutaneous fistual
      is reported. We subsequently review the literature of this exceedingly rare
      condition.

PMID- 18610682
TI  - Smoking associated with malignancy, hypertension, chronic obstructive pulmonary
      disease and concurrent coronary artery disease: report of nine cases.
AB  - Tobacco smoking in any form is a major risk factor for coronary artery disease
      (CAD), hypertension (HTN), chronic obstructive pulmonary disease (COPD), oral,
      nasopharyngeal, bronchial and other visceral malignancies. Cessation of smoking
      exerts considerable beneficial effect on development, recurrence and prognosis of
      these diseases. Present communication is based on the study of nine cases who had
      concurrent CAD, HTN, COPD and mitotic and/or pre malignant lesions due to
      unabated smoking. The youngest patient was a 35-year-old male having a smoking
      index of 300, presenting with acute coronary syndrome, COPD, HTN and buccal
      leukoplakia. Associated genitourinary malignancies in two cases and osteosarcoma
      in one case was an unusual presentation. These cases highlight the prognosis and
      public health implications of continuous smoking.

PMID- 18610683
TI  - Resection of a endobronchial hamartoma by electrocautery and argon plasma
      ablation via fiberoptic bronchoscopy.
AB  - Endobronchial hamartoma is a rare benign tumour of the lung that may present with
      bronchial obstruction. We present a case of endobronchial hamartoma that was
      resected and ablated with electrocautery and argon plasma coagulation by
      fiberoptic bronchoscopy.

PMID- 18610685
TI  - Indian Journal of Chest Diseases and Allied Sciences: 50 years of publication.

PMID- 18610684
TI  - Profile of pollen allergies in patients with asthma, allergic rhinitis and
      urticaria in Hyderabad.

PMID- 18610686
TI  - Left ventricular dysfunction and extravascular fluid in the lung: physiological
      basis for symptoms.
AB  - The essential feature of left ventricular dysfunction is an increase in left
      atrial pressure and pulmonary venous congestion leading to a fluid flux across
      the pulmonary microvasculature. Small acute increases (< 10 mmHg) in left atrial
      pressure enhance the extravascular fluid volume in the airways and activate the
      rapidly adapting receptors (RAR). With larger increases in left atrial pressure
      (approximately 25 mmHg) both the RAR and the C-fiber receptors in the airways and
      the alveoli are activated. Activation of RAR causes a reflex increase in
      respiratory rate, tracheal tone and mucus secretion from the airways. It appears
      that small increases in extravascular fluid volume of the airways also cause a
      reflex diuresis which is mediated by activation of neuronal nitric oxide synthase
      in the renal medulla. In contrast, when left atrial pressure is elevated
      chronically, further small increments in extravascular fluid volume of the
      airways no longer stimulate the RAR. The reflex diuresis is also not evident
      under these circumstances. However, the RAR continue to be activated by
      increments in left atrial pressure in excess of 25 mmHg. It is suggested that the
      RAR of the airways play a significant role in monitoring changes in the
      extravascular fluid volume of the airways and mediate the reflexes which are
      associated with the symptomatology of acute left ventricular dysfunction.

PMID- 18610687
TI  - Medical mycology in India (1957-2007): contributions by the VPCI Mycoses Group.

PMID- 18610688
TI  - Tissue reaction patterns in respiratory infections: a practical approach to a
      cytological diagnosis.
AB  - Infection of the respiratory tract, particularly indolent and chronic disease can
      be a diagnostic dilemma. Infections associated with immunosuppressive states
      often require an accurate early diagnosis because it impacts outcome. A wide
      variety of specimens, such as, sputum, bronchoalveolar lavarge (BAL),
      transthoracic or transbronchial fine needle aspiration (FNA) can be employed.
      Cytopathology is diagnostic when the causative organism can be identified failing
      which, direction can be given to further investigation by examination of the
      tissue reaction patterns. Three types of reactions seen in lung infections act as
      clues to the diagnosis: (a) necrosis, (b) inflammatory reactions, and (c)
      epithelial changes with little inflammation. Identification of tissue reaction
      types limits the diagnostic possibilities and facilitates the diagnostic process.

PMID- 18610689
TI  - Homocysteine, folic acid and coronary artery disease: possible impact on
      prognosis and therapy.
AB  - Within the past four decades, the efforts of investigators worldwide have
      established the amino acid homocysteine (Hcy) as an important factor in
      arteriosclerosis and ageing. The amino acid homocysteine is a unique candidate
      for the study of different age-related pathological conditions, namely vascular
      diseases, dementia disorders and late-life depression, due to its multiple roles
      in different pathways leading to atherosclerosis and neurotoxicity. Especially,
      the role of homocysteine in predicting risk for atherothrombotic vascular disease
      has been evaluated in several observational studies in a large number of
      patients. These studies show that the overall risk for vascular disease is small,
      with prospective, longitudinal studies reporting a weaker association between
      homocysteine and atherothrombotic vascular disease compared to retrospective case
      control and cross-sectional studies. Furthermore, randomised controlled trials of
      homocysteine-lowering therapy have failed to prove a causal relationship. On the
      basis of these results, there is currently insufficient evidence to recommend
      routine screening and treatment of elevated homocysteine concentrations with
      folic acid and other vitamins to prevent atherothrombotic vascular disease.

PMID- 18610690
TI  - Tropical parasitic lung diseases.
AB  - Though parasitic lung diseases are frequently seen in tropical countries, these
      are being increasingly reported from many parts of the world due to globalisation
      and travel across the continents. In addition, the emergence of human
      immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS),
      the frequent use of immunosuppressive drugs in many diseases and the increasing
      numbers of organ transplantations have resulted in a renewed interest in many
      tropical parasitic lung diseases. This review outlines the recent developments in
      the pathogenesis, diagnosis and management of common and rare parasitic lung
      diseases.

PMID- 18610691
TI  - Fibreoptic bronchoscopy in the diagnosis of sputum smear-negative pulmonary
      tuberculosis: current status.
AB  - Sputum smear-negative pulmonary tuberculosis (SSN-PTB) is a common problem faced
      by clinicians. Performing fibreoptic bronchoscopy (FOB), and subjecting the
      bronchoscopic secretions/transbronchial lung biopsy (TBLB) material to
      conventional diagnostic methods of smear, mycobacterial culture and
      histopathology appears to be helpful in the diagnosis of SSN-PTB. Application of
      polymerase chain reaction (PCR) may be helpful as an adjunctive method in the
      appropriate clinical setting. The FOB facilitates rapid diagnosis and offers the
      additional advantage of the diagnosis of several conditions that may mimic PTB.
      However, FOB is an invasive procedure, and is associated with the risk of
      transmission of tuberculosis (TB) and other infections. It is costly, and is not
      widely available in the developing countries. In developed countries with no
      limitations on resources, early FOB seems to be the best course of action in a
      patient with suspected SSN-PTB. In resource-poor settings, where transmission of
      TB is high, sputum induction with hypertonic saline can be useful in adding to
      the diagnostic yield. If the TB suspect still remains induced sputum smear
      negative, and if the pre-test probability of the patient having PTB is high,
      starting antituberculosis treatment (ATT) and closely monitoring the patient and
      reserving FOB to those patients who do not seem to improve/deteriorate or those
      who have a negative spontaneously expectorated/induced sputum culture (if
      performed and available) seems to be a practically useful approach. Proper
      precautions must be followed to disinfect the bronchoscope in between use so as
      to minimise the risk of nosocomial transmission of infection.

PMID- 18610692
TI  - Recent advances in the assessment and management of chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a syndrome of progressive airflow
      limitation caused by an abnormal inflammatory reaction of the airways and lung
      parenchyma. It stems from chronic tobacco smoking, and indoor air pollution, and
      bronchospasm is the predominant cause of the symptoms. The condition is the
      result of environmental insult and host reaction that is likely to be genetically
      predetermined. Chronic obstructive pulmonary disease exhibits expiratory airflow
      limitation due to abnormalities in the airways and/or lung parenchyma. The
      disease begins with an asymptomatic phase and onset of the symptomatic phase
      develops with a fall in forced expiratory volume in one second (FEV1) below 70%
      of the predicted value. There is reduction in diffusing capacity, hypoxaemia and
      alveolar hypoventilation. However, it is intriguing why only a fraction of
      smokers develop clinically relevant COPD.

PMID- 18610693
TI  - Chronic obstructive pulmonary disease: knowing what we mean, meaning what we say.
AB  - Chronic obstructive pulmonary disease (COPD) is defined in several different ways
      using different criteria based on symptoms, physiological impairment and
      pathological abnormalities. While some use COPD to mean smoking related chronic
      airway disease, others include all disorders causing chronic airway obstruction.
      When COPD is used as a broad descriptive term, specific disorders that cause
      chronic airway obstruction remain under-diagnosed and the prevalence estimates
      vary considerably. The lack of agreement over the precise terminology and
      classification of COPD has resulted in widespread confusion. Terminology includes
      definition, diagnostic criteria, and a system for staging severity. Recently,
      COPD is defined more clearly and diagnosed using precise criteria that include
      tobacco smoking greater than 10 pack years, symptoms and airway obstruction on
      spirometry. A multi-dimensional severity grading system, the BODE (body mass
      index, obstruction, dyspnoea, and exercise tolerance) index has been designed to
      assess the respiratory and systemic expressions of COPD. This review proposes
      that the broad group of chronic disorders of the airways (with or without airway
      obstruction) be called chronic airway disease (CAD). The term COPD should be used
      exclusively for tobacco smoking related chronic airway disease. Chronic airway
      obstruction or obstructive lung disease may be used to define those conditions
      with airways obstruction caused by factors other than tobacco smoking. The
      aetiology may be appended to the label, for example, chronic airway
      obstruction/obstructive lung disease associated with bronchiectasis, chronic
      airway obstruction/obstructive lung disease associated with obliterative
      bronchiolitis or chronic airway obstruction/obstructive lung disease due to
      biomass fuel/occupational exposure.

PMID- 18610694
TI  - Oxygen therapy: important considerations.

PMID- 18610695
TI  - Assessment of control in asthma: the new focus in management.
AB  - Several evidence-based guidelines on the management of asthma have been developed
      in the last two decades. There is a consensus that a stepped-up approach with
      anti-inflammatory drugs based on severity forms the cornerstone of treatment.
      Goals of management have been defined. Studies in several countries have however
      shown that a large majority of patients have failed to attain the goals of
      treatment. This has led to a reconsideration of strategy of management. The focus
      is now shifting to an assessment and a treatment approach based on control. The
      objective is to achieve and monitor to maintain control. The previous treatment
      algorithms based on assessment of severity are being discarded. It has been
      emphasised that the state of control is a dynamic one and therefore a regular
      assessment and modifications of treatment according to changes in its level are
      necessary. There is a need to use some method to assess control. A wide range of
      techniques to assess control are available that can be used depending on the
      requirements, settings and resources. Assessment of control may be an informal
      global judgement by the physician or simple tools may be used. Several formal
      instruments to assess the state of control have also been developed and validated
      in different settings. These allow a more objective and a quantitative
      evaluation. Control needs to be assessed at every visit of a patient and
      treatment adjusted accordingly.

PMID- 18610696
TI  - Aspergillus-associated hypersensitivity respiratory disorders.
AB  - The mould Aspergillus is responsible for a gamut of respiratory diseases ranging
      from saprobic colonisation to rapidly invasive disseminated disease. The clinical
      spectrum of Aspergillus-associated hypersensitivity respiratory disorders
      includes Aspergillus induced asthma, allergic bronchopulmonary aspergillosis
      (ABPA), allergic Aspergillus sinusitis (AAS) and hypersensitivity pneumonitis.
      Inhalant allergens, in patients with allergic asthma, play a key role in bringing
      about the inflammation present in the airways, and fungi are increasingly being
      recognised as important inhalant allergens. Aspergillus is linked to asthma in
      more ways than one. In the asthmatic subjects, the fungal spores are trapped in
      the thick and viscid secretions that are usually present in the airways. This
      generally develops in atopic subjects and is sustained by continuous inhalation
      of Aspergillus antigens, triggering asthma that may be more severe in form.
      Aspergillus induced asthma is yet to receive the recognition that it deserves.
      Allergic bronchopulmonary aspergillosis is the best known form of allergic
      aspergillosis and is an emerging disease in India. An immunologically mediated
      lung disease, ABPA occurs predominantly in patients with asthma. A set of
      diagnostic criteria is required as there is no single test that establishes the
      diagnosis apart from demonstration of central bronchiectasis with normal tapering
      bronchi, a feature considered to be pathognomonic of ABPA. Radiologically, ABPA
      is characterised by 'transient pulmonary infiltrates' or 'fleeting shadows',
      often confused with pulmonary tuberculosis. A comparatively more recently
      recognised clinical entity, AAS is characterised by mucoid impaction in the
      paranasal sinuses which is akin to that in ABPA. Although it appears that the
      patient with ABPA provides a favourable milieu for the occurrence of AAS, it is
      perhaps surprising that in spite of similar histopathological features the co
      existence of both these diseases has not often been reported. Aspergilloma, a
      fungal ball that appears in a pre-existing cavity due to saprobic colonisation of
      Aspergillus species, can often present with asthma. The association of ABPA and
      aspergilloma is also known. Although cavitation can occur in ABPA, the co
      existence of ABPA with aspergilloma is rather uncommon. Aspergillomas may
      function as a nidus for antigenic stimulation in a genetically predisposed
      individual resulting in the occurrence of ABPA. Contemporaneous occurrence of
      ABPA, AAS and aspergilloma has also been reported. Screening all asthmatic
      subjects for Aspergillus sensitisation could identify those with a severe form of
      the disease as well as those at risk for developing ABPA. Furthermore,
      concomitant occurrence of ABPA and AAS is now being increasingly recognised, and
      AAS must be excluded in all patients with ABPA.

PMID- 18610697
TI  - Sleep and sleep disorders.
AB  - Sleep is a complex neurological state, with its primary function of providing
      rest and restoring the body's energy levels. The importance of sleep could be
      seen from the fact that people spend about one-third of their lifespan in sleep.
      Normal human sleep is divided into non-rapid eye movement (NREM) and rapid eye
      movement (REM) sleep, and the alteration between NREM and REM occurs about 4-5
      times during a night of normal sleep. Human NREM sleep could be classified into
      four stages, namely, stage I, II, III and IV, representing successively deeper
      stages of sleep. Sleep is an active rhythmic neural process produced by several
      brain areas, of which the preoptic and other basal forebrain areas play a major
      role in the generation of NREM sleep. Interaction of the pedenculo-pontine and
      lateral dorsal tegmental areas with the dorsal raphae nucleus and locus
      coeruleus, is important for REM sleep generation. Suprachiasmatic nucleus of the
      hypothalamus and the pineal gland ensure that sleep and wakefulness follow a
      circadian periodicity of nearly 24 hours. Alterations in the quality, quantity
      and pattern of sleep result in sleep disorders. Persistent and repeated
      interruption of sleep affects the health of an individual. Undiagnosed and
      untreated wake/sleep complaints cause not only misery to the sufferer, but it
      also has socio-economic consequences. Sleep disorders cover a wide spectrum of
      diseases. Though there are more than 100 identified sleep/wake disorders, most
      sleep complaints can be categorised into five, namely, hypersomnia, insomnia,
      circadian rhythm disorders, parasomnias, and sleep disorders associated with
      mental, neurological, and other medical disorders. Researches during the last 50
      years, and the advances made in clinical sleep medicine, have lead to more
      effective treatments for the myriad human sleep disorders. It is not possible to
      assign a specific reason for many of the sleep disorders, but some aspects of
      sleep and wakefulness are genetically influenced. But, most commonly, sleepiness
      during waking hours, results from volitional or forced sleep deprivation during
      previous nights, due to social, economic and environmental reasons. So, public
      awareness about sleep disorders should be an essential part of any programme
      aimed at global management of sleep disorders.

PMID- 18610698
TI  - Overview and implications of obstructive sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is a leading public health problem both in the
      developed and developing nations. However, awareness regarding diagnostic
      options, management and consequences of untreated OSA remains inadequate. In
      developing nations, the resources for adequate sleep medicine facilities are
      scarce. Therefore, there is a need for low cost, simple and accurate diagnostic
      and therapeutic modalities exists. Untreated OSA leads to excessive daytime
      sleepiness, diminished performance and an overall poor quality of life. The role
      of OSA in promoting insulin resistance, atherosclerosis, hypertension and a
      procoagulant state has now been established. Newer insights into the biochemical
      and genetic mediators of OSA have raised hopes regarding the development of a
      "cure". However, as of now, continuous positive airway pressure (CPAP) therapy
      remains the first-line treatment. Though its use improves the quality of life as
      well as metabolic derangements observed in OSA, patients' acceptance remains low.
      Its high cost and long-term use are also cumbersome. Newer modes of delivering
      CPAP, oral appliances and upper airway surgery are the other options available.
      It is hoped that their appropriate use to increase patients' compliance may
      improve the quality of life as well as provide a survival benefit.

PMID- 18610699
TI  - Sleep in the intensive care unit.
AB  - Sleep is commonly disrupted in intensive care unit patients. The causes of this
      sleep disruption include the underlying medical illness itself, intensive care
      unit (ICU) environment, psychological stress, and effects of many medications and
      other treatments used to help those who are critically ill. The purpose of this
      review is to discuss the relevant literature in this regard, in order to improve
      the knowledge and recognition of this problem by health care providers. Also
      general and specific integrative steps to improving sleep of patients in the ICU
      is also described.

PMID- 18610700
TI  - Adjusting to patients' increasing financial responsibility.

PMID- 18610701
TI  - Commercial payment for selected imaging procedures calendar years 2005-06.

PMID- 18610702
TI  - Effectively managing your collection agencies.

PMID- 18610703
TI  - DNA collage and personalized medicine.

PMID- 18610704
TI  - Informed consent for procedures in the Neonatal Intensive Care Unit.
AB  - Establishing those procedures that require documentation of specific informed
      consent in a Neonatal Intensive Care Unit (NICU) setting remains controversial.
      Although documentation of specific informed consent for blood transfusions is
      universally mandated, consent for other procedures such as umbilical
      catheterizations may or may not be obtained and/or documented. In a retrospective
      study, medical charts of 116 neonates were reviewed to determine if consent for
      umbilicalvein and arterial catheterizations, blood transfusions, and procedures
      that require documentation of consent at Connecticut Children's Medical Center
      (CCMC), had been obtained. Consent for blood transfusions was obtained 98%
      (87/89) of the time compared with 34% (64/191) for umbilical vein and arterial
      catheterizations combined. Variables contributing to decreased consent rates for
      catheterizations were explored as were alternatives that would increase the
      consent rate. National Neonatal Intensive Care Unit consent policies from eight
      children's hospitals were reviewed to further evaluate current practice. Future
      research investigating expectations of families would be useful to create policy
      revisions.

PMID- 18610705
TI  - A comparison of outcomes for patients receiving implantable cardioverter
      defibrillators for primary vs secondary-prevention.
AB  - OBJECTIVE: Compare characteristics and outcomes of patients receiving implantable
      cardioverter defibrillators (ICDs) for primary vs secondary cardiac arrest
      prevention. METHODS: Patients in this cohort study were identified from a
      prospectively collected ICD database from June 1999 to August 2003 and divided
      into groups based on whether they received their ICD for primary or secondary
      prevention of cardiac arrest. Patient follow-up continued until August of 2006
      and the occurrence of appropriate ICD shocks, inappropriate ICD shocks, and
      mortality were compared between groups. RESULTS: Of the 437 patients, 80.8% were
      male, 70.3% had coronary disease, and the mean age was 65.7+/-13.1 years. At
      baseline, primary-prevention patients had lower left ventricular ejection
      fraction (LVEF), use of a single chamber device and utilization of beta blockers
      and antiarrhythmics while having a greater use of biventricular pacing as
      compared to secondary-prevention patients. Over the first 12 months after
      implantation, the primary-prevention group was 43.0% less likely to receive an
      appropriate shock for ventricular arrhythmias (P=0.002) and 34.2% less likely to
      have an appropriate shock over the entire follow-up period (P=0.018). The
      incidence of inappropriate ICD shocks over the first 12 months after implantation
      and over the entire follow-up period was similar between groups (P=0.900 and
      P=0.217, respectively) as was mortality (P=0.228 and P=0.757, respectively).
      CONCLUSIONS: Primary-prevention patients are characteristically different in
      numerous ways from secondary-prevention patients, but despite having a greater
      risk of experiencing appropriate shocks, exhibit a similar risk of inappropriate
      shocks and mortality over an average follow-up time exceeding 41 months.

PMID- 18610706
TI  - An update on recent advances in asthma management.

PMID- 18610707
TI  - Town and city medical societies in Connecticut.

PMID- 18610708
TI  - A unique faith-based medical organization: the Christian Medical Fellowship.
AB  - The Association of American Medical Colleges has challenged medical educators to
      be role models for the incorporation of faith into the art and practice of
      medicine. The Christian Medical Fellowship (CMF) is one approach toward
      accomplishing this goal. CMF is a nonprofit organization that brings health,
      hope, and healing, to and through the health-care community, providing
      transformational love locally and internationally. CMFseeks to support the
      caregiver while serving the underserved. CMF accomplishes this through a three
      fold approach: promoting individual faith, community outreach, and international
      missions. CMF provides a framework to assist health-care providers in meeting
      their own spiritual needs along with those of their patients. The Christian ethic
      teaches that Jesus touched and changed lives by showing love and compassion,
      while meeting physical as well as spiritual needs. The goal of CMF is to do the
      same. The CMF vision is to replicate CMF's three-fold ministry by fostering the
      development of independent, self-supporting CMF chapters to serve throughout the
      USA and the world. CMF plans to develop a fully functioning faith-based
      Fellowship Program in conjunction with a CMF faith-based clinic and an
      international hospital. The growth of CMF and the advancement of the educational
      experiences are a result of many committed, disciplined, and focused individuals
      motivated by a deep faith in the original vision. We look to the future with
      anticipation, as we continue to bridge the gap between faith and the science of
      medicine.

PMID- 18610709
TI  - A guide to Connecticut's certificate-of-need process.

PMID- 18610710
TI  - Saving primary care by sharing the wealth: blasphemy?

PMID- 18610711
TI  - The painful teaching point.

PMID- 18610712
TI  - The Hospital of Saint Raphael. 1958.

PMID- 18610713
TI  - Participation in MEDICINE: a senior lament.

PMID- 18610714
TI  - "Teaming" up for quality health care.

PMID- 18610715
TI  - Legislative advocacy: another successful session.

PMID- 18610716
TI  - Practice assessments: back to basics.

PMID- 18610717
TI  - PPI inhibitors.

PMID- 18610718
TI  - [Skin diseases throughout life: from pediatric to geriatric dermatology].

PMID- 18610719
TI  - [Dermatoporosis: an emerging syndrome].
AB  - With the increase in lifespan, we are now more often experiencing a further
      dimension of skin aging, which is no longer only cosmetic, but also functional,
      in the sense that the skin has lost its protective mechanical functions. We
      propose to group the different manifestations and implications of this chronic
      cutaneous insufficiency/fragility syndrome under the umbrella term of
      "dermatoporosis". Molecular mechanisms implying hyaluronate-CD44 pathways seem to
      play an important role in the pathogenesis. Dermatologists should be aware of
      this emerging syndrome and function as key players in its prevention and therapy.
      Randomized clinical trials should demonstrate which intervention may best prevent
      and/or reverse dermatoporosis.

PMID- 18610720
TI  - [Genetic dermatology clinics: a practical approach].
AB  - There are numerous genodermatoses and different types of transmission. Recent
      technological progress of molecular genetics allows to confirm or specify
      increasingly the clinical diagnosis and to better define the risk of recurrency.
      A close collaboration of dermatologists and geneticists has been established at
      CHUV since several years. By means of clinical examples we illustrate the
      organisation and procedures of this pluridisciplinary consultation which aims to
      optimize the clinical management of rare genetic diseases.

PMID- 18610721
TI  - [The biological treatments for moderate to severe plaque psoriasis].
AB  - Psoriasis is a chronic inflammatory skin disorder that can cause substantial
      disability. The recognition of psoriasis as an immunologically mediated disease
      led to the development of agents that specifically target key steps in the
      pathological process. In this review, we focus on the mechanism of action, the
      efficacy and the safety data of the new biological treatments: alefacept,
      efalizumab, etanercept, infliximab and adalimumab.

PMID- 18610722
TI  - [Cutaneous lesions in genetic tumor syndromes].
AB  - Genetic tumor syndromes reflect an inherited predisposition to develop benign and
      malignant tumors. Increased frequency of neoplasms within the family or occurring
      at an early age are clinical clues for a possible underlying genetic
      susceptibility. Awareness of their associated cutaneous manifestations can
      facilitate early detection of risk for tumors. The goal of this article is to
      review clinical and molecular features of some genetic tumor syndrome which
      present with skin involvement at birth or during childhood.

PMID- 18610723
TI  - [Inflammation and auto-immunity: an update on the NOD-like receptors and their
      clinical role].
AB  - Clinical and molecular research on inflammation has soared tremendously thanks to
      the discovery of Toll-like receptors (TLRs). These efforts have resulted in the
      recent identification and characterization of a new class of proteins called NOD
      like receptors (NLR), which are intracellular analogs of the TLRs. These
      molecules act as true sensors of the dangers encountered by the cell and are
      essential for the initiation of the inflammatory response. Their implication in
      the pathogeny of numerous auto-inflammatory and autoimmune diseases
      revolutionizes our understanding of the mechanisms underlying the development of
      these diseases. We discuss here these major discoveries as well as their clinical
      implications.

PMID- 18610724
TI  - [Atypical staphylococcal scalded skin syndrome: it could be battered child
      syndrome].
AB  - A case of pseudo staphylococcal scalded skin syndrome is presented and discussed
      within the clinical spectrum of the battered child syndrome. The authors
      underline the behavior of the parents in this setting, which can mislead the
      physician in charge. Dermatologic symptoms are important to make a diagnosis of
      the battered child syndrome.

PMID- 18610725
TI  - [Gastroesophageal reflux: a possible cause of paroxysmal laryngeal dyspnea].
AB  - An important number of patients are referred to the ENT specialist because of
      extraoesophageal manifestations of gastroesophageal reflux. The most alarming
      symptom is a paroxysmal dyspnea secondary to a laryngospasm. The patients report
      a laryngeal choking sensation associated to an aphonia. We report three cases of
      laryngospasm secondary to acid gastric reflux. The diagnosis was made with the
      clinical history, a laryngeal examination and a 24-hour pH-monitoring enabled us
      to demonstrate a clear temporal relation between the reflux episodes and the
      choking episodes. In conclusion, the pharyngo-laryngeal reflux is a possible
      cause of laryngospasm. In our three patients, a high dose antiacid treatment was
      efficient to bring a lasting relief of the symptoms.

PMID- 18610726
TI  - [Teddy bear clinic].

PMID- 18610728
TI  - [Maternal nutrition and fetal sex].

PMID- 18610727
TI  - [Risks in organ removal after cardiac arrest (2)].

PMID- 18610729
TI  - American Health Lawyers Association 2006-2007 year in review.
AB  - Every year, the American Health Lawyers Association assembles aYear in Review
      summary of the leading developments in case law, legislation, and administrative
      actions affecting healthcare. This article provides a comprehensive overview of
      these developments, demonstrating the increasingly complex and high profile
      nature of health law in the United States, as well as the inextricable links
      between health law and life sciences law.

PMID- 18610730
TI  - Tort reform by regulation: FDA prescription drug labeling rules and preemption of
      state tort claims.
AB  - In 2006, the Food and Drug Administration (FDA) asserted in the preamble to a
      revised physician labeling rule for prescription drugs that FDA labeling
      requirements preempt state common law failure to warn claims. The FDA's action
      reflects a wider effort of administrative agencies to preempt conflicting state
      law requirements. The debate over preemption raises a set of difficult issues,
      including the sufficiency of agency safety review, the scope of administrative
      deference, and federalism. This article surveys the background to the 2006 FDA
      labeling rule and the Supreme Court's recent preemption jurisprudence in leading
      cases such as Cippollone v. Liggett Group, Inc., and Geier v. American Honda
      Motor Corp.

PMID- 18610731
TI  - Scientific misconduct in research.
AB  - Allegations of research misconduct, especially in federally-supported research,
      raise the specter of contentious, difficult confrontations. It is the obligation
      of the institution at which the research is conducted to ensure that a fair,
      competent, and thorough review of each allegation occurs. Recently revised Public
      Health Service research misconduct regulations set forth clear guidance and
      detailed requirements for institutional policies, inquiries, and investigations.
      Counsel to research institutions that receive federal support for research must
      be familiar with these regulations. Failure to prepare for, or respond quickly
      and compliantly to, allegations of research misconduct may result in injustice to
      an accused researcher, make definitive determinations impossible, expose an
      institution to regulatory penalties, and damage the reputation of both
      researchers and the institution.

PMID- 18610732
TI  - ERISA as an obstacle to fair share legislation and other state initiatives to
      expand coverage to the uninsured and underinsured.
AB  - As states experiment with legislation designed to address problems of healthcare
      affordability and accessibility by requiring employers to offer or spend more on
      employee health benefit plans, courts increasingly will be called upon to
      determine whether such mandates run afoul of ERISA. This article examines the
      potential impact of existing case law on current legislative initiatives.

PMID- 18610733
TI  - Executive Order 13,422, OMB's good guidance practices, and implications for
      health rulemaking and guidance.
AB  - In early 2007, President Bush issued Executive Order 13,422, extending executive
      review to significant guidance documents, requiring the designation of a
      politically-appointed Regulatory Policy Officer (RPO) within each agency, and
      strengthening the review and consultation role of the Office of Management and
      Budget's (OMB) Office of Information and Regulatory Affairs (OIRA). Almost
      simultaneously, the OMB issued its Final Bulletin for Good Guidance Practices
      (GGP) to address the growing agency practice of using non-binding guidance
      documents in lieu of rulemaking procedures to direct the conduct of regulated
      entities. This paper describes the evolution of executive review of rulemaking
      and guidance, the impetus for the current changes, and the possible implications
      of the executive order and OMB's Final Bulletin on Good Guidance Practices for
      the health law arena.

PMID- 18610734
TI  - What must entities do to comply with Deficit Reduction Act requirements for
      information on federal and state False Claims Act provisions?

PMID- 18610735
TI  - New chemotherapy strategies for gastric cancer.
AB  - Gastric cancer chemotherapy has entered a new era with the introduction of new
      drugs such as S-1, irinotecan (CPT-11), paclitaxel and docetaxel. Recent phase
      III studies have indicated that S-1 monotherapy, a remnant reference arm from a
      previous study, was not inferior to 5-FU alone, and that the combination of S-1
      with cisplatin and CPT-11 showed higher efficacy than S-1 alone with tolerable
      side-effects for advanced and recurrent gastric cancer. In the adjuvant setting,
      S-1 monotherapy prolonged survival following surgery compared with surgery alone
      after curative extended (D2) lymph-node dissection for stage II/III gastric
      cancer. However, some issues remain, such as the sequence of several duplet
      chemotherapies, treatment following cases of S-1 failure, the relative efficacy
      of doublet and triplet therapies, and the impact of molecular-targeting.

PMID- 18610736
TI  - Role of transporter genes in cisplatin resistance.
AB  - The 50% inhibitory concentration (IC50) values for cisplatin from 60 cell lines
      of the National Cancer Institute (NCI), USA, were correlated with the microarray
      based mRNA expression levels of 55 transporter genes. The transporters are known
      to be involved in multiple drug resistance and belong to different classes, e.g.
      lysosomal H+ transporting ATPases, Cu2+ transporting ATPases, glutamate
      transporters of the solute carrier family 31, copper transporters of the solute
      carrier family 31, and ATP-binding cassette (ABC) transporter genes. The
      expression levels of 17 genes represented by 21 clones correlated significantly
      with the IC50 values for cisplatin. Hierarchical cluster analysis further enabled
      the prediction of the sensitivity or resistance of these cell lines to cisplatin
      with respect to the mRNA expression of these set of transporter genes under
      study. One among the 17 genes studied is ATP7B which is involved in the transport
      of copper ions across the cell membrane into the cell. We conclude that our
      microarray-based approach is a feasible and effective tool in identifying
      prognostic markers for drug resistance in antitumor therapy.

PMID- 18610737
TI  - NLNQ-1, a 2-[3-(2-nitro-1-imidazolyl) propylamino]-3-chloro-1,4-naphthoquinone,
      as a hypoxia-selective cytotoxin and radiosensitizer.
AB  - BACKGROUND: Compounds bearing two independent redox centers are considered bis
      bioreductive agents and usually demonstrate increased hypoxic selectivity with
      exposure time due to different requirements for reduction of each center. We have
      synthesized a novel 2-[3-(2-nitro-1-imidazolyl)propylamino]-3-chloro-1,4
      naphthoquinone (NLNQ-1), through Michael addition. NLNQ-1, which combines a
      naphthoquinone (with a relatively high one electron reduction potential) with a 2
      nitroimidazole (with a relatively low one electron reduction potential), could
      perform as a more potent hypoxia-selective cytotoxin and radiosensitizer.
      MATERIALS AND METHODS: NLNQ-1 was evaluated in V79 cells under hypoxic/normoxic
      conditions, alone or with radiation, by using the clonogenic assay. RESULTS:
      Clearly NLNQ-1 was a more potent cytotoxin than the 2-alkylsulfonyloxy
      naphthoquinones (VH-compounds), developed previously in our lab, demonstrating
      hypoxic and aerobic IC50 values at microM rather than mM concentrations. As a
      radiosensitizer of hypoxic cells, NLNQ-1 was superior to the best bis
      nitroimidazolic compound, NNB (which combines a 2-nitroimidazole with a 5
      nitroimidazole), demonstrating a C1.6 value of 25.4 microM (ca. 25 fold lower
      than that of NNB), whereas its in vitro therapeutic index (IC50A/C1.6) ranged
      from 5.3-13.2. CONCLUSION: NLNQ-1 could be used as a novel scaffold for bis
      bioreductive agents that can be properly modified for further optimization of
      their hypoxia-selective toxicity and radiosensitization properties.

PMID- 18610738
TI  - Comparative study of the alkyl and peroxy radical-scavenging activity of 2-t
      butyl-4-methoxyphenol (BHA) and its dimer, and their theoretical parameters.
AB  - BACKGROUND: 2-t-Butyl-4-methoxyphenol (BHA) has considerable toxicity and
      undesirable potential tumor-promoting activities. To clarify the free radical
      mechanism of BHA-induced toxicity, the comparative radical-scavenging activity of
      BHA and its dimer (bis-BHA, 3,3'-ditert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'
      diol) with or without 2-mercapto-1-methylimidazole (MMI) was studied using the
      induction period method. MATERIALS AND METHODS: The induction period and
      propagation rate (Rp) were determined by differential scanning calorimetry (DSC)
      monitoring of polymerization of methyl methacrylate, initiated by the thermal
      decomposition of benzoyl peroxide (a source of the peroxy radical, PhCOO*) or
      2,2'-azobisisobutyronitrile (a source of the alkyl radical, R*) under nearly
      anaerobic conditions. The anti-1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical- and
      O2(-)-scavenging activities were also investigated. Furthermore, theoretical
      parameters were calculated from the DEFT/B3LYP and HF/6-31G*//B3LYP levels.
      RESULTS: For both PhCOO* and R* the inhibition rate constant (k(inh)) for BHA and
      bis-BHA was almost identical, but a marked decrease in the Rp(inh)/Rp(con) was
      found for the former. The BHA/MMI mixture (1:1 molar ratio) oxidized by R*
      reduced the total radical-scavenging activity by approximately 20% . BHA showed
      lower anti-DPPH radical- and higher O2(-)-scavenging activity. CONCLUSION: Upon
      PhCOO* or R* scavenging, BHA with a lower BDE, IP(koopman's), electronegativity,
      and electrophilicity value, but not bis-BHA with higher corresponding values,
      highly suppressed propagation. This may be due to the formation of highly
      reactive free-radical intermediates, which are potentially toxic.

PMID- 18610739
TI  - Methylene blue in place of acridine orange as a photosensitizer in photodynamic
      therapy of osteosarcoma.
AB  - We recently established a unique therapeutic modality for musculoskeletal
      sarcomas, combining acridine orange (AO) with photodynamic surgery (PDS),
      photodynamic therapy (PDT) and radiodynamic therapy (RDT); excellent results were
      obtained in the inhibition of local tumor recurrence after intralesional
      excision. However, AO is not yet approved for clinical use and intravenous
      injection. Therefore, methylene blue (MB), which has a very similar chemical
      structure to AO and is already in clinical use for other diseases, was
      investigated. In vitro studies using mouse osteosarcoma (LM8) cells revealed that
      MB-PDT had a strong cytocidal effect and that MB was not radiosensitive, showing
      no effect in RDT. In vivo studies showed that MB did not specifically accumulate
      in mouse osteosarcoma tissue and that it did not inhibit tumor growth. MB is not
      a better photosensitizer than AO in PDS, PDT and RDT for osteosarcoma.

PMID- 18610740
TI  - Gamma-H2AX - a novel biomarker for DNA double-strand breaks.
AB  - When DNA damage, whether it is endogenous or exogenous, forms double stranded
      breaks (DSBs), it is always followed by the phosphorylation of the histone, H2AX.
      H2AX is a variant of the H2A protein family, which is a component of the histone
      octomer in nucleosomes. It is phosphorylated by kinases such as ataxia
      telangiectasia mutated (ATM) and ATM-Rad3-related (ATR) in the PI3K pathway. This
      newly phosphorylated protein, gamma-H2AX, is the first step in recruiting and
      localizing DNA repair proteins. DSBs can be induced by mechanisms such as
      ionizing radiation or cytotoxic agents and subsequently, gamma-H2AX foci quickly
      form. These foci represent the DSBs in a 1:1 manner and can be used as a
      biomarker for damage. An antibody can be raised against gamma-H2AX which can
      therefore be visualized by immunofluorescence through secondary antibodies. The
      detection and visualization of gamma-H2AX by flow cytometry allow the assessment
      of DNA damage, related DNA damage proteins and DNA repair. Gamma-H2AX also has
      other applications in the detection of genomic damage caused by cytotoxic
      chemical agents and environmental and physical damage, especially in the context
      of cancer treatment and therapy.

PMID- 18610741
TI  - Heat shock proteins as novel therapeutic targets in cancer.
AB  - Heat shock proteins (HSPs) are evolutionarily conserved molecules synthesised by
      cells exposed to sub-lethal stresses. Acting as molecular chaperones, HSPs
      protect cells from environmental stress damage by assisting in proper folding and
      stabilisation of proteins. In addition, they help to sequester severely damaged
      proteins for degradation. Owing to the nature of their function, HSPs are often
      found to be overexpressed in a wide range of cancers. Members of the HSP family
      have been implicated in cancer growth as promoting tumour cell proliferation as
      well as inhibiting cellular death pathways. In recent years, several HSP90 client
      proteins have been validated as clinically important therapeutic targets for
      treatment of cancer, and inhibitors of HSP90 have emerged as potentially
      beneficial anticancer agents. This review explores the involvement of HSPs in
      cancer and the development of several anticancer agents with promising
      therapeutic applications.

PMID- 18610742
TI  - Induction of differentiation in human promyelocytic cells by the isothiocyanate
      sulforaphane.
AB  - BACKGROUND: The consumption of cruciferous vegetables has long been associated
      with a reduced risk for the occurrence of cancer at various sites. This
      protective effect is associated with their isothiocyanate content. Sulforaphane
      (SFN) is by far the isothiocyanate most extensively studied to uncover the
      mechanisms behind this chemoprotection. In the present study, the ability of SFN
      to induce cytodifferentiation and apoptosis in a leukemia cell line was
      investigated. MATERIALS AND METHODS: Cells were treated with different
      concentrations of SFN (0-100 microM). Analysis of cell differentiation was
      performed by nonspecific/specific acid esterase activity. Apoptosis induction was
      performed by flow cytometry. RESULTS: SFN induced cytodifferentiation toward both
      granulocytic and macrophagic lineage, mediated by the involvement of
      phosphatidylinositol 3-kinase/protein kinase C. It also caused a significant
      increase in the apoptotic cell fraction. CONCLUSION: These findings suggest that
      SFN may be a promising antileukemic agent and should encourage further
      investigation as regards its chemotherapeutic potential.

PMID- 18610743
TI  - Target specificity of 188Re-labeled B27.1 monoclonal antibodies to ovarian cancer
      cells in vivo.
AB  - BACKGROUND: Currently we are exploring a new multistep pretargeting approach
      involving administration of a bispecific antibody (B27.1 x P54) which has an anti
      CA-125 (B27.1) and antibiotin (P54) paratope. It is followed by the
      administration of radiolabeled biotinylated liposomes to target the 188Re to the
      ovarian cancer cells. As a preliminary step to realize this goal, we determined
      the target specificity of the monoclonal antibodies (B27.1) to the ovarian cancer
      cells in vivo. MATERIALS AND METHODS: B27.1 monoclonal antibodies were
      photoreduced using UV light and incubated with reduced 188Re for 30 min at
      25degreesC. 188Re-labeled B27.1 antibodies were purified using size exclusion
      chromatography. A comparative biodistribution of Re-B27.1 and 188Re was performed
      in nude mice xenografted with NIH:OVCAR-3 cells. RESULTS: While free rhenium
      distributed preferentially into thyroid and stomach with insignificant
      accumulation in the cancer cells, about 20% of the injected dose of 188Re-B27.1
      was recovered in ascites cells with insignificant localization in other organs
      four hours after administration. CONCLUSION: The study validates the affinity of
      the B27.1 antibodies to the ovarian cancer cells in vivo.

PMID- 18610744
TI  - Anti-HIV and vitamin C-synergized radical scavenging activity of cacao husk
      lignin fractions.
AB  - Cacao husk lignin fractions, prepared by acid precipitation and 50% ethanol
      precipitation showed unexpectedly higher anti-human immunodeficiency virus (HIV)
      activity, as compared with the corresponding fractions from the cacao mass,
      amounting to the level comparable with that of popular anti-HIV compounds. The
      cacao husk lignin fractions also showed anti-influenza virus activity, but did
      not show antibacterial activity. The cacao husk lignin fractions synergistically
      enhanced the superoxide anion and hydroxyl radical scavenging activity of vitamin
      C. The cacao husk lignin fractions stimulated nitric oxide generation by mouse
      macrophage-like cells, to a level higher than that attained by lipopolysaccharide
      (LPS). The present study suggests the functionality of cacao husk lignin
      fractions as complementary alternative medicine.

PMID- 18610745
TI  - COX-2 as possible target for the inhibition of PGE2 production by Rikko-san in
      activated macrophage.
AB  - We have previously reported that Rikko-san (RKS) inhibited the lipopolysaccharide
      (LPS)-stimulated prostaglandin (PG) E2 in mouse macrophage-like RAW264.7 cells
      without affecting the expression of cyclooxygenase (COX)-2. Here RKS inhibition
      of the enzyme activity of both COX-1 and COX-2 proteins was investigated. Western
      blot analysis showed that RKS did not significantly change the S-nitrosylated COX
      2 protein level. On the other hand, RKS inhibited the PG production catalyzed by
      purified COX-2, more effectively than that catalyzed by purified COX-1. These
      results suggest that RKS inhibits the PGE2 production by selectively inhibiting
      the COX-2 activity in activated macrophages.

PMID- 18610746
TI  - Prevention of lethal tumor growth and generation of long-lasting immunity in vivo
      using CD137L and interleukin-12 gene transfer.
AB  - In a wide range of solid tumors, overexpression of CD137L has been shown to
      induce tumor immunity partly due to the stimulation of CD8+ CTL, which was even
      increased when immunotherapy with interleukin-12 (IL12) was additionally
      employed. However, little in known regarding hematologic neoplasias in this
      respect. Of the 8 animals receiving IL12-secreting tumor cells, 2 died. Animals
      treated with CD137L-expressing tumor cells and the combination group, all animals
      survived. Interestingly, re-challenge with wild-type tumor cells was rejected by
      all animals in the CD137L group and all remaining animals in the IL12 group,
      while these in the control group died. IL12- and CD137L-transfected plasmocytoma
      cells prevented tumor growth and induced long-lasting immunity. Our results
      warrant follow-up for future clinical use in patients with myeloma.

PMID- 18610747
TI  - Synthesis, in vivo antileukemic evaluation and comparative study of novel 5alpha
      7-keto steroidal esters of chlorambucil and its active metabolite.
AB  - Recent structure-antileukemic activity studies showed that the steroidal part of
      complex molecules containing DNA alkylators does not play only the role of the
      "biological carrier". New such compounds designed to possess an allylic 7-ketone
      showed enhanced antileukemic potency compared with derivatives with a simple
      steroidal skeleton. In order to investigate whether the enhancement of the
      antileukemic potency is attributed to the introduction of the 7-ketone or to the
      Delta5-7-keto conjugated steroidal system we decided to reduce the Delta5 double
      bond. The 5alpha-7-keto-steroidal skeletons synthesized were tethered to
      chlorambucil and phenyl acetic acid's nitrogen mustard and studied against
      leukemia P338 in vivo. The reduction of the double bond had a negative impact on
      the antileukemic potency since the comparative study of the novel derivatives
      showed that a series of very potent Delta 5-7-keto-steroidal esters were
      converted by this modification to compounds with marginally accepted activity.

PMID- 18610748
TI  - Inhibitory effect of nordihydroguaiaretic acid and its tetra-acetylated
      derivative on respiration and growth of adenocarcinoma TA3 and its multiresistant
      variant TA3MTX-R.
AB  - The effects of nordihydroguaiaretic acid (NDGA) and its tetraacetylated
      derivative (NDGATA) on the growth, oxygen consumption, adenosine 5'-triphosphate
      (ATP) level and viability of mouse mammary adenocarcinoma TA3 and its
      multiresistant variant TA3-MTX-R cell lines were determined. NDGA inhibited
      mitochondrial carbonyl cyanide m-chlorophenylhydrazone (CCCP)-stimulated oxygen
      consumption in mouse liver and tumor cells when glutamate plus malate or
      succinate was added as substrate. The effects were considerably weaker when
      respiration was supported by duroquinol, indicating that NDGA inhibited primarily
      mitochondrial electron flow located at some point before ubiquinone. Although
      NDGATA only inhibited the electron flow through complex I, it was more efficient
      and selective than NDGA because mouse liver mitochondria were significantly less
      sensitive to it than both tumor cell lines tested. NDGA and NDGATA inhibited
      mitochondrial ATP synthesis and, consequently, cell viability and growth rate
      were also decreased. NDGA and NDGATA inhibited the growth of intramuscularly
      implanted tumor cells, indicating that NDGATA was also antineoplastic in vivo. In
      conclusion, NDGATA is cytotoxic to tumor cells, provoking selective induction of
      mitochondrial dysfunctions, which could be interesting as potential antitumoral
      agent.

PMID- 18610749
TI  - Juice of eclipta prostrata inhibits cell migration in vitro and exhibits anti
      angiogenic activity in vivo.
AB  - BACKGROUND: The invasion of cancer cells is critical for metastasis. The effects
      of Eclipta prostrata, a Thai medicinal plant, on invasion, migration and adhesion
      of cancer cells were investigated and the anti-angiogenic activity in vivo was
      evaluated. MATERIALS AND METHODS: In vitro invasion and migration assays were
      performed in modified Boyden chambers. In vivo anti-angiogenic activity was
      determined using the chick chorioallantoic membrane (CAM) assay. RESULTS: E.
      prostrata juice inhibited cancer invasion and migration, without affecting cell
      adhesion. Cell migration was inhibited in a variety of cancer cell types and in
      endothelial cells, with IC50 values of 31-70 microg/ml, much lower than the IC50
      values for cytotoxicity of 203-1,217 microg/ml for cancer cells and >4,000
      microg/ml for endothelial cells. Fifty percent inhibition of angiogenesis by E.
      prostrata juice was observed at 200 microg/egg. CONCLUSION: E. prostrata juice
      inhibited cancer and endothelial cell migration in vitro and also showed in vivo
      anti-angiogenic activity.

PMID- 18610750
TI  - Ethanol extract of Dunaliella salina induces cell cycle arrest and apoptosis in
      A549 human non-small cell lung cancer cells.
AB  - The ethanol extract of Dunaliella salina (EDS) on proliferation and apoptosis in
      the A549 human lung cancer cell line and their associated protein expressions
      were investigated. After 24 and 48 h treatment, MTT assay showed that 25
      microg/ml of EDS significantly reduced A549 cell proliferation by 25.2% (p<0.05)
      and 48.3% (p<0.01), respectively. To explore its molecular mechanisms in
      regulating cell proliferation, we first showed that EDS markedly reduced A549
      proliferation via inhibition of BrdU incorporation at 25 microg/ml by 65.8%
      (p<0.001). By cytometric analysis, EDS was found to induce apoptosis and cell
      cycle arrest in the G0/G1 phase. In the DNA gel electrophoresis assay, EDS (25,
      50 and 100 microg/ml) induced significant apoptosis at 48 h. Annexin V/Propodium
      iodide double staining demonstrated that administration of EDS (25 microg/ml) in
      12, 24 and 48 h induces apoptosis of 27.7%, 30.7%, and 38.7%. Western blotting
      assay demonstrated that EDS significantly increased the expression of cyclin
      dependent kinase (CDK) inhibitors p53 and p21 and death-receptor proteins Fas and
      FasL. Bax expression was also elevated by treatment with EDS. Our data suggested
      that EDS could influence the antiproliferative effects and induce cell cycle
      G0/G1 arrest and apoptosis of A549 lung cancer cells.

PMID- 18610751
TI  - MDR-reversal activity of chalcones.
AB  - The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to
      inhibit the transport activity of P-glycoprotein was studied. Flow cytometry was
      applied in multidrug-resistant human mdr1 gene-transfected mouse lymphoma cells
      (L 5178 Y). The reversal of multidrug resistance (MDR) was investigated by
      measuring the accumulation of rhodamine-123 in cancer cells. Verapamil was
      applied as a positive control. The majority of the tested compounds were proved
      to be effective inhibitors of the outward transport of rhodamine-123. In the MTT
      test, chalcones 2, 3, 5 and 7 exhibited the strongest antiproliferative effects,
      with 50% inhibitory dose (ID50) =0.19, 0.19, 0.29 and 0.14 microg/mL,
      respectively. The least effective compounds were 1, 4, 8 and 11, with ID50 values
      in the range of 1.5-3.5 microg/mL. The antiproliferative effect was shown to be
      affected by the type of substitution at the p-position on ring B. Chalcone 7,
      with a p-chloro group on ring B, was the most effective in MDR reversal, causing
      a marked increase in drug accumulation from 0.4 to 40 microg/mL. In combination
      with epirubicin, compound 7 displayed synergistic properties while compound 3
      exhibited an additive effect. The data presented here indicated that some calcone
      derivatives can be regarded as effective compounds for reversal of MDR.

PMID- 18610752
TI  - The biological role of chondroitin sulfate in cancer and chondroitin-based
      anticancer agents.
AB  - Chondroitin sulfate proteoglycans (CSPGs) such as versican accumulate in tumor
      stroma and play a key role in tumor growth and invasion. The high expression of
      CSPGs in fast growing tissues and cells is correlated with chondroitin sulfate
      (CS) chains and the sulfation pattern. The negatively charged CS chains interact
      with a large number of ligands and receptors and activate signalling pathways
      which stimulate tumor growth. However, the role of chondroitin sulfate in cancer
      promotion seems to be controversial, as recent studies support the use of
      modified CS as a potent anticancer agent. In this review, the biological roles of
      CSPGs in cancer and the anticancer effects of modified CS are presented and
      discussed.

PMID- 18610753
TI  - Effects of morin on the bioavailability of tamoxifen and its main metabolite, 4
      hydroxytamoxifen, in rats.
AB  - This study examined the effect of morin on the bioavailability and
      pharmacokinetics of tamoxifen and its metabolite, 4-hydroxytamoxifen, in rats. A
      single dose of tamoxifen was administered to rats intravenously (2 mg/kg) or
      orally (10 mg/kg), with or without morin (3 or 10 mg/kg). The presence of morin
      significantly altered the pharmacokinetics of the orally administered tamoxifen.
      Compared with the oral control group (given tamoxifen alone), the total body
      clearance (CL/F) of tamoxifen in the presence of morin was significantly reduced
      (by 35.9-40.8%, p<0.01). The area under the plasma concentration-time curve
      (AUC(0-infinity)) and the peak plasma concentration (Cmax) of tamoxifen
      significantly (p<0.05 for 3 mg/kg of morin, p<0.01 for 10 mg/kg of morin)
      increased by 50.6-68.9% and 65.1-80.9%, respectively. Consequently, the absolute
      bioavailability (AB) of tamoxifen in the presence of morin was 37.4-40.5%, which
      was enhanced significantly (p<0.05) compared with the oral control group (23.9%).
      The relative bioavailability (RB) of tamoxifen was 1.56 to 1.68 times higher than
      the control group. The increased bioavailability of tamoxifen is likely to be due
      to the decrease in the first-pass metabilism by the intestines and liver. Morin
      at a dose of 10 mg/kg significant increased the AUC(0-infinity), of 4
      hydroxytamoxifen (by 50.9%, p<0.05) but the metabolite:parent ratio (MR) of 4
      hydroxytamoxifen was not altered significantly, suggesting that the formation of
      4-hydroxytamoxifen is not affected considerably by morin. The increased
      bioavailability of tamoxifen in the presence of morin should be taken into
      consideration for dosage regimens due to potential drug interaction.

PMID- 18610754
TI  - A study of immunoendocrine strategies with pineal indoles and interleukin-2 to
      prevent radiotherapy-induced lymphocytopenia in cancer patients.
AB  - BACKGROUND: Lymphocytopenia represents one of the most evident side-effects of
      radiotherapy (RT), particularly in the case of irradiation of pelvis, since it is
      the main location of bone-marrow proliferating cells in adults. Because of the
      fundamental role of lymphocytes in suppressing anticancer immunity, RT-induced
      lymphocytopenia could negatively influence the prognosis of cancer patients and
      the therapeutic efficacy of RT itself. In experimental conditions, the biological
      toxicity of irradiation appeared to be reduced by antioxidant agents, such as
      pineal hormones melatonin. A preliminary study was conducted to evaluate the
      influence of different immunobiological strategies with pineal indoles melatonin
      (MLT), 5 methoxytriptamine (5-MTT) or low-dose IL-2, the lymphocyte growth
      factor, on pelvic irradiation-induced lymphocytopenia in cancer patients
      suffering from rectal cancer or uterine cervix carcinoma. PATIENTS AND METHODS:
      The study included 20 consecutive patients, who underwent pelvic irradiation for
      a total dose of 50.4 Gy. The patients were randomized to be concomitantly treated
      with MLT alone, with MLT plus 5-MTT or with s.c. low-dose IL-2 . RESULTS: RT
      induced a significant decline in the mean number of lymphocytes while neither MLT
      alone, nor MLT plus 5-MTT were able to significantly reduce this decline.
      Conversely, IL-2 caused a statistically significant reduction of the RT-induced
      effect, so that the mean number of lymphocytes was significantly higher in
      patients concomitantly treated by IL-2 than in the other groups. CONCLUSION: This
      preliminary study showed that low-dose IL-2 was sufficient to reduce, even though
      not to completely abrogate, RT-induced lymphocytopenia. Further studies with
      different schedules and doses of IL-2 will be required to optimize the protective
      effect of IL-2 on irradiation-induced lymphocytopenia in humans.

PMID- 18610755
TI  - [Metformin and type 2 diabetes: the UKPDS experience].

PMID- 18610756
TI  - [PPAR receptors at the crossroads of obesity, diabetes and cardiovascular
      diseases].

PMID- 18610757
TI  - [Another view of the transcriptional effect of insulin].

PMID- 18610758
TI  - [Clinical results concerning glitazones].

PMID- 18610759
TI  - [Can glitazones provide protection of the kidneys?].

PMID- 18610760
TI  - [Intensification of insulin therapy in type 2 diabetics].

PMID- 18610761
TI  - [Intensive insulin therapy in type 2 diabetes: obstacles: observance and elements
      of response].

PMID- 18610762
TI  - [Prescription, adjustment and surveillance od bolus treatment in type 1 or type 2
      diabetes].

PMID- 18610763
TI  - Caloric restriction and longevity.

PMID- 18610764
TI  - [Orchestration of homeostasis of glucose metabolism].

PMID- 18610765
TI  - [A fatal and sweet desire].

PMID- 18610766
TI  - [Apollinare Bochardat Prize 2007. Regulation and glucose signal transduction in
      the liver: implication of the transcription factor CHREBP].

PMID- 18610767
TI  - [Dialog between life and death].

PMID- 18610768
TI  - [How to explain the rebirth of the beta cell in terms of sacrifice and delivery].

PMID- 18610769
TI  - [Type 1 diabetes: the rediscovery of insulin].

PMID- 18610770
TI  - Effects of weighted vests and sled towing on sprint kinematics.
AB  - In this study, we compared sprint kinematics of sled towing and vest sprinting
      with the same relative loads. Twenty athletes performed 30-m sprints in three
      different conditions: (a) un-resisted, (b) sled towing, and (c) vest sprinting.
      During sled towing and vest sprinting, external loads of 15% and 20% of body mass
      were used. Sprint times were recorded over 10 and 30 m. Sagittal-plane high-speed
      video data were recorded at 5, 15, and 25 m from the start. Relative to the un
      resisted condition, sprint time increased (7.5 to 19.8%) in both resisted
      conditions, resulting mainly from decreased step length (-5.2 to -16.5%) with
      small decreases in step frequency (-2.7 to -6.1%). Sled towing increased stance
      phase duration (14.7 to 26.0%), trunk angle (12.5 to 71.5%), and knee angle (10.3
      to 22.7%), and decreased swing phase duration (-4.8 to -15.2%) relative to the un
      resisted condition. Vest sprinting increased stance phase duration (12.8 to
      24.5%) and decreased swing phase duration (-8.4 to -14.4%) and trunk angle (-1.7
      to -13.0%). There were significant differences between the two resisted
      conditions in trunk, thigh, and knee angles. We conclude that sled towing and
      vest sprinting have different effects on some kinematics and hence change the
      overload experienced by muscle groups.

PMID- 18610771
TI  - The relationship between discus throwing performance and combinations of selected
      technical parameters.
AB  - The aim of this study was to determine the relationship between discus throwing
      performance and the following technical parameters: hip-shoulder and shoulder-arm
      separation, trunk forward-backward tilt, throwing-arm elevation angles, and the
      absolute and relative throwing procedure phase times. Videographic data of 51
      male and 53 female discus throwers' competitive performances were captured during
      major meets. The three-dimensional coordinates of 21 body landmarks and the
      discus were obtained for each thrower's best trial using direct linear
      transformation. The technical parameters were reduced from the three-dimensional
      data at six critical instants during the throwing procedure. Hierarchical
      stepwise multiple regression analyses were performed to determine the relative
      influence of linear combinations of the technical parameters on discus throwing
      performance. Specific techniques associated with linear combinations of certain
      technical parameters were identified using canonical correlations. Males and
      females were analysed separately. Suggestions for controlling the height of
      release and the vertical component of the speed of release using an effective
      technique are made.

PMID- 18610772
TI  - Orthotic control of rear foot and lower limb motion during running in
      participants with chronic Achilles tendon injury.
AB  - This study examined the kinematic effects of orthoses in participants with a
      history of chronic Achilles tendon injury. Twelve participants ran at self
      selected speeds on a treadmill with and without customized orthoses. Joint and
      segment angles including leg abduction, calcaneal, eversion, ankle dorsiflexion,
      and knee flexion angles were calculated from three-dimensional data throughout
      stance. Five footfalls were obtained for each participant and condition.
      Statistical tests revealed an increase in maximum eversion with orthoses (P <
      0.001, eta(p)2 = 0.642). In the individual participant analysis, this was evident
      in 9 of 12 participants. Trends towards increased eversion range of motion and
      decreased ankle dorsiflexion maximum and range of motion angles were also
      observed. Increased eversion was unexpected as all devices were designed to
      provide pronation control as deemed necessary by the podiatrist. Despite this,
      participants reported between 50 and 100% (average 92%) relief from symptoms with
      the use of orthoses. Further analysis of the angle-time curves and coordination
      between angular measures is recommended.

PMID- 18610773
TI  - Three-dimensional kinematics of the lower limbs during forward ice hockey
      skating.
AB  - The objectives of the study were to describe lower limb kinematics in three
      dimensions during the forward skating stride in hockey players and to contrast
      skating techniques between low- and high-calibre skaters. Participant motions
      were recorded with four synchronized digital video cameras while wearing
      reflective marker triads on the thighs, shanks, and skates. Participants skated
      on a specialized treadmill with a polyethylene slat bed at a self-selected speed
      for 1 min. Each participant completed three 1-min skating trials separated by 5
      min of rest. Joint and limb segment angles were calculated within the local
      (anatomical) and global reference planes. Similar gross movement patterns and
      stride rates were observed; however, high-calibre participants showed a greater
      range and rate of joint motion in both the sagittal and frontal planes,
      contributing to greater stride length for high-calibre players. Furthermore,
      consequent postural differences led to greater lateral excursion during the power
      stroke in high-calibre skaters. In conclusion, specific kinematic differences in
      both joint and limb segment angle movement patterns were observed between low-
      and high-calibre skaters.

PMID- 18610774
TI  - Comparison of split double and triple twists in pair figure skating.
AB  - In this study, we compared the kinematic variables of the split triple twist with
      those of the split double twist to help coaches and scientists understand these
      landmark pair skating skills. High-speed video was taken during the pair short
      and free programmes at the 2002 Salt Lake City Winter Olympics and the 2003
      International Skating Union Grand Prix Finals. Three-dimensional analyses of 14
      split double twists and 15 split triple twists from eleven pairs were completed.
      In spite of considerable variability in the performance variables among the
      pairs, the main difference between the split double twists and split triple
      twists was an increase in rotational rate. While eight of the eleven pairs relied
      primarily on an increased rotational rate to complete the split triple twist,
      three pairs employed a combined strategy of increased rotational rate and
      increased flight time due predominantly to delayed or lower catches. These
      results were similar to observations of jumps in singles skating for which the
      extra rotation is typically due to an increase in rotational velocity; increases
      in flight time come primarily from delayed landings as opposed to additional
      height during flight. Combining an increase in flight time and rotational rate
      may be a good strategy for completing the split triple twist in pair skating.

PMID- 18610775
TI  - Ground reaction forces and kinematics of plant leg position during instep kicking
      in male and female collegiate soccer players.
AB  - The players' ability to achieve the greatest distance in kicking is determined by
      their efficiency in transferring kinetic energy from the body to the ball. The
      purpose of this study was to compare the kinetics and kinematics of the plant leg
      position between male and female collegiate soccer players during instep kicking.
      Twenty-three soccer players (11 males and 12 females) were filmed in both the
      sagittal and posterior views while performing a maximal instep kick. Plant leg
      kinetic data were also collected using an AMTI 1000 force platform. There were no
      significant differences between the sexes in plant leg position, but females had
      significantly greater trunk lean, plant leg angle, and medial-lateral ground
      reaction force than the males. Males showed higher vertical ground reaction
      forces at ball contact, but there were no significant differences in ball speed
      at take-off between the sexes. Ball speed at take-off was inversely related to
      peak anterior-posterior ground reaction force (-0.65). The anatomical differences
      between the sexes were reflected in greater trunk lean and lower leg angle in the
      females.

PMID- 18610776
TI  - A comparison of muscle activations during traditional and abbreviated tennis
      serves.
AB  - The abbreviated tennis serve is a relatively novel modification of the
      traditional serve that has been reported to provide performance advantages over
      the traditional technique. However, there are limited objective data regarding
      the benefits and biomechanics of the abbreviated serve; no data exist that
      describe shoulder muscle activations during the abbreviated serve. The purpose of
      this study was to compare muscle activations between the traditional and
      abbreviated serves. Electromyographic data were collected for the anterior and
      posterior deltoid, infraspinatus, middle trapezius, latissimus dorsi, serratus
      anterior, and pectoralis major. When muscle activations were compared during each
      serve phase, no significant differences were observed between the traditional and
      abbreviated tennis serve techniques, indicating that the traditional and
      abbreviated serves are similar regarding shoulder muscle activations. These
      results could have implications for performance of and injury related to the
      abbreviated versus traditional serve technique. Although the abbreviated serve
      has anecdotally been described as advantageous, the present data do not indicate
      any significant advantages or disadvantages in performing the abbreviated serve
      technique versus the traditional serve.

PMID- 18610777
TI  - The influence of deformation on barbell mechanics during the clean pull.
AB  - For simplicity of biomechanical analyses, the weightlifting barbell is typically
      modelled as a rigid, nondeformable object. Most coaches and weightlifters,
      however, are aware of the elastic nature of the barbell, and its influence on the
      successful completion of lifting attempts. Variables such as velocity, work
      performed, and power output are indicators of the quality of performance during
      the snatch, clean, and related weightlifting pulling movements. The aim of this
      study was to establish whether differences exist in determining these
      biomechanical parameters when the centre of the barbell is analysed compared with
      each end of the barbell. Nine men performed three maximal-effort repetitions in
      the clean pull exercise at 85% of their self-reported single repetition maximum
      (1-RM) clean (90-155 kg) using a barbell instrumented for mechanical analysis.
      Results indicated that peak barbell speed was 5-30% (P < 0.05) lower for the
      centre of the barbell than the ends. Although differences (P < 0.05) in kinetic
      and potential energy were found between the centre and ends of the bar,
      differences between total work performed were small (< 6%; P < 0.05) and no
      differences were observed for average power (P > 0.05). Although approximately
      the same work and power occur for the centre and ends of the barbell, they
      manifest as different kinematics as a result of the elastic nature of the
      equipment. The elastic characteristics should be considered when selecting
      instrumentation and variables for research involving barbells. Coaches should be
      aware of the elasticity of barbells, including selecting appropriate viewing
      angles as well as understanding how deformation may affect the ends of the
      barbell relative to the centre.

PMID- 18610778
TI  - Development and validation of a method to directly measure the cable force during
      the hammer throw.
AB  - The development of cable force during hammer-throw turns is crucial to the throw
      distance. In this paper, we present a method that is capable of measuring cable
      force in real time and, as it does not interfere with technique, it is capable of
      providing immediate feedback to coaches and athletes during training. A strain
      gauge was mounted on the wires of three hammers to measure the tension in the
      wire and an elite male hammer thrower executed three throws with each hammer. The
      output from the gauges was recorded by a data logger positioned on the lower back
      of the thrower. The throws were captured by three high-speed video cameras and
      the three-dimensional position of the hammer's head was determined by digitizing
      the images manually. The five best throws were analysed. The force acting on the
      hammer's head was calculated from Newton's second law of motion and this was
      compared with the force measured via the strain gauge. Qualitatively the time
      dependence of the two forces was essentially the same, although the measured
      force showed more detail in the troughs of the force-time curves. Quantitatively
      the average difference between the measured and calculated forces over the five
      throws was 76 N, which corresponds to a difference of 3.8% for a cable force of
      2000 N.

PMID- 18610779
TI  - Accuracy of sequential sub-field synchronization of multiple digital camcorders
      through numerical optimization.
AB  - The use of digital camcorders in biomechanical analyses can introduce errors due
      to inter-camera time offsets. The faster the motion being recorded the greater
      the error. A sequential synchronization method was developed in this study to
      achieve sub-field camera synchronization for multiple camcorders through
      numerical optimization. A recreational golfer performed ten drives while being
      recorded with four digital camcorders (60-Hz sampling rate). Video signals were
      sampled at 10,000 Hz to determine the actual inter-camera time offsets. The
      optimized inter-camera time offsets were computed based on three markers placed
      on the shaft, each separated by 200 mm. The inter-camera time offset error was
      computed as the difference between the optimized and actual inter-camera time
      offsets. The inter-camera time offset error reduced on average from 0.518 to
      0.019 fields (1 field = 16.7 ms) or less due to sequential optimization. The
      optimized global reconstruction errors were less than 19% of the unadjusted
      values. It was concluded that the ability to synchronize multiple (two or more)
      cameras using a sequential sub-field optimization strategy promises to extend the
      use of relatively inexpensive digital camcorders to motions considered too fast
      for the low field rates of such cameras. The sequential approach presented
      provides a balance between computation time and reconstruction accuracy.

PMID- 18610780
TI  - Shock and impact reduction in moderate and strenuous landing activities.
AB  - Shock reduction has been well studied in moderate activities such as walking and
      running. However, there is a clear lack of research concerning shock wave
      transmission and reduction in more strenuous landing activities. In this study,
      we examined the impact of shock transmission and reduction in landing activities
      with varied mechanical demands. Ten active males were recruited for the study.
      They performed five successful step-off landing trials from each of five heights:
      30, 45, 60, 75, and 90 cm. Right sagittal kinematics, ground reaction forces, and
      acceleration were recorded simultaneously. Impact frequencies were analysed using
      a discrete Fast Fourier Transform and power spectral density was computed.
      Increased range of motion for the ankle, knee, and hip joints was observed at
      higher landing heights. The peaks of the vertical ground reaction force, forehead
      and tibial accelerations, and eccentric muscle work by lower extremity joints
      were increased with increased landing heights. The peak head power spectral
      density was severely attenuated at higher frequencies but the peak tibia power
      spectral density did not demonstrate this trend. Shock reduction showed increased
      reduction at higher frequencies, but minimal changes across five landing heights.
      Unlike the responses observed for walking and running, the shock reduction did
      not show significant improvement with elevated mechanical demands.

PMID- 18610781
TI  - A proposed ethical framework for vaccine mandates: competing values and the case
      of HPV.
AB  - Debates over vaccine mandates raise intense emotions, as reflected in the current
      controversy over whether to mandate the vaccine against human papilloma virus
      (HPV), the virus that can cause cervical cancer. Public health ethics so far has
      failed to facilitate meaningful dialogue between the opposing sides. When
      stripped of its emotional charge, the debate can be framed as a contest between
      competing ethical values. This framework can be conceptualized graphically as a
      conflict between autonomy on the one hand, which militates against government
      intrusion, and beneficence, utilitarianism, justice, and nonmaleficence on the
      other, which may lend support to intervention. When applied to the HPV vaccine,
      this framework would support a mandate based on utilitarianism, if certain
      conditions are met and if herd immunity is a realistic objective.

PMID- 18610782
TI  - Religion, genetics, and sexual orientation: the Jewish tradition.
AB  - This paper probes the implications of a genetic basis for sexual orientation for
      traditional branches of Judaism, which are struggling with how accepting to be of
      noncelibate gays and lesbians in their communities. The paper looks at the
      current attitudes toward homosexuality across the different branches of Judaism;
      social and cultural factors that work against acceptance; attitudes toward
      science in Jewish culture; and the likelihood that scientific evidence that
      sexual orientation is at least partly genetically determined will influence
      Jewish scholars' and leaders' thinking on this issue.

PMID- 18610783
TI  - The liberty principle and universal health care.
AB  - A universal entitlement to health care can be grounded in the liberty principle.
      A detailed examination of Rawls's discussion of health care in Justice as
      Fairness shows that Rawls himself recognized that illness is a threat to the
      basic liberties, yet failed to recognize the implications of this fact for health
      resource allocation. The problem is that one cannot know how to allocate health
      care dollars until one knows which basic liberties one seeks to protect, and yet
      one cannot know which basic liberties to protect until one knows how health care
      dollars will be allocated. The solution is to design the list of basic liberties
      and the health care system in tandem so as to fit each other, such that every
      citizen is guaranteed a set of basic liberties and access to the health services
      needed to secure them.

PMID- 18610784
TI  - Debating ethical expertise.
AB  - This paper explores the relevance of the debate about ethical expertise for the
      practice of clinical ethics. We present definitions, explain three theories of
      ethical expertise, and identify arguments that have been brought up to either
      support the concept of ethical expertise or call it into question. Finally, we
      discuss four theses: the debate is relevant for the practice of clinical ethics
      in that it (1) improves and specifies clinical ethicists' perception of their
      expertise; (2) contributes to improving the perception of moral competence of non
      ethicists; (3) gives insight into complementary styles of argumentation of
      ethicists and non-ethicists; and (4) contributes to the awareness of the problem
      of profession-building of (clinical) ethicists.

PMID- 18610785
TI  - Medical tourism: crossing borders to access health care.

PMID- 18610786
TI  - Endocrine disrupting chemicals, covering analysis, occurrence and removal from
      wastewaters and receiving waters.

PMID- 18610787
TI  - Treatment and removal strategies for estrogens from wastewater.
AB  - Natural and synthetic steroidal estrogens (estrone, 17beta-estradiol and 17alpha
      ethinylestradiol) are endocrine disrupters, that are discharged consistently from
      the sewage treatment works into surface waters, thereby causing endocrine
      disrupting effects to aquatic organisms at trace concentrations (nanogram per
      litre). Several years of research have been focused on their fate, behaviour and
      removal in the environment but primarily in the sewage treatment works which acts
      as a sink for these compounds. This review attempts to summarize the factors
      involved in the removal of these chemicals from the sewage treatment works.
      Biological processes, and to a limited extent physio-chemical properties, play a
      vital role in the endocrinal deactivation of these compounds. The efficiency of
      these processes is highly dependent on operating parameters (such as sludge
      retention time, redox potential, etc) that govern the secondary treatment process
      of a functional sewage treatment works. Although advanced treatment technologies
      are available, cost and operational considerations do not make them a sustainable
      solution.

PMID- 18610788
TI  - Biodegradation of endocrine disrupters: case of 17beta-estradiol and bisphenol A.
AB  - The biodegradation of 17 beta-estradiol (E2) and bisphenol A (BPA) was compared
      to that of a reference pollutant, sodium benzoate (SB), known for its high
      biodegradability. The biodegradation was measured using the Sturm test (ISO 9439
      modified Sturm test). The susceptibility of the target pollutants to be degraded
      by microorganisms of activated sludge from a wastewater treatment plant (WWTP)
      was evaluated by the production of carbon dioxide (CO2). Sorption experiments
      onto inactivated sludge were carried out to assess the contribution of sorption
      in E2 and BPA removal during biological treatment in a WWTP. E2 was more adsorbed
      than BPA onto inactivated sludge, probably making it less accessible to
      assimilation by microorganisms. In fact, E2 was less biodegradable than BPA with
      66% and 74% of theoretical CO2 formation (Th(co2)) in 28 days, respectively.
      However, E2 showed faster biodegradation than BPA due to the shorter adaptation
      time of the microorganisms to start the assimilation. Final concentrations were
      measured and revealed that, under Sturm test conditions, E2 was totally removed
      from the aqueous phase while some traces of BPA were detected. This result could
      be explained by the lower adsorbability of BPA observed in adsorption experiments
      onto inactivated sludge. To investigate competition in a bi-component solution,
      Sturm tests were carried out with BPA/SB and E2/SB. Moreover, the biodegradation
      curves obtained did not indicate a toxicity of the target compounds towards
      microorganisms, which rapidly degraded SB. In the case of BPA/SB, an inflection
      in the curve confirmed the adaptation time of 4-5 days for BPA to be degraded.

PMID- 18610789
TI  - Analysis of endocrine disrupting compounds in wastewater and drinking water
      treatment plants at the nanogram per litre level.
AB  - The determination of steroid hormones, alkylphenolic compounds and bisphenol A at
      the ng l(-1) level in environmental water samples (surface water and WasteWater
      Treatment Plant samples (WWTP)) is performed by a specific analytical procedure.
      Pre-concentration by solid-phase extraction conditions was optimized using C18
      cartridges for steroid hormones and polymeric Oasis HLB cartridges for phenolic
      compounds. Identification and quantification were performed using a LCMS/MS
      system with electrospray ionization in the negative mode for both compound
      families. For steroid hormones, the need to have limits of detection lower than
      0.5 ng l(-1) in WWTP samples led to the improvement of a purification step on
      silica cartridges. In the case of the phenolic compounds, no purification was
      required because of their lower estrogenicity. The limits of detection in WWTP
      effluents ranged between 0.02 ng l(-1)and 0.21 ng l(-1) for steroid hormones and
      0.4 and 10.2 ng l(-1) for phenolic compounds. The method was then applied to
      determine concentrations of the target compounds at each step of a WWTP. The
      process efficiencies were evaluated. Finally, concentrations were measured in
      influents and effluents of a Drinking Water Treatment Plant showing the complete
      removal of estrogenicity.

PMID- 18610790
TI  - Modeling of decomposition characteristics of estrogenic chemicals during
      ozonation.
AB  - The purposes of this study were to develop a refined model for simulation of
      ozonation of estrogenic chemicals under different conditions and to investigate
      the behaviors of estrogenic by-products using the model. In the cases of
      ozonation of 17-estradiol (E2), bisphenol-A (BPA) and nonylphenol (NP) in aqueous
      solution, it can be concluded that the liquid film resistances are larger than
      bulk resistances, and thus most of the reaction occurs in liquid bulk. E2, BPA
      and NP are easily decomposed producing by-products of ozonation, but the
      estrogenicity of these chemicals and the by-products reduced with increase in
      ozonation time. Through this research, ozonation was shown to be a promising
      method to decompose E2, BPA and NP and to reduce the estrogenicity of these
      chemicals.

PMID- 18610791
TI  - Enhanced disappearance of dicofol by water hyacinth in water.
AB  - The efficiency and primary mechanism of phytoremediation of water contaminated
      with dicofol, an organochlorine pesticide, by water hyacinth (Eichhornia
      crassipes) was investigated. After 10 days of incubation in nutrient solution at
      25 +/- 1 degree C, the remaining dicofol which was spiked initially at 1 mg l(-1)
      was 0.05 and 0.26 mg l(-1) in the non-sterile planted and non-sterile unplanted,
      0.07 and 0.31 mg l(-1) in the sterile planted and sterile unplanted treatments,
      respectively. The half-life of dicofol in nutrient solutions was reduced to 59-68
      h in the planted treatments from 118-137 h in the unplanted treatments. The
      accumulated dicofol in water hyacinth plant decreased by 41-53% after the plant
      had grown for 7 days in dicofol-free nutrient solution. Two phytoprocesses were
      found to be most important in the remediation of dicofol contaminated water: (i)
      uptake, accumulation and phytodegradation of dicofol by the plant, accounted for
      50% of the removal of the spiked dicofol, and (ii) microbial degradation
      associated with the rhizosphere, contributed about 7% to dicofol removal. Water
      hyacinth may thus be a good candidate for development as a phytoremediation
      system for dicofol-contaminated water.

PMID- 18610792
TI  - Distribution of persistent organochlorine residues in sediments from the
      Songhuajiang River, Northeast China.
AB  - Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in surface
      sediments from 10 sampling sites of the Songhuajiang River were analyzed to
      evaluate their potential pollution and hazards. Gas chromatography equipped with
      a 63Ni electron capture detector (GC-ECD) and gas chromatography/mass
      spectrometer (GC/MS) methods were used, respectively. The total concentrations of
      13 OCPs varied from 4.26 to 18.45 ng g(-1). Sigma HCH (alpha-HCH, beta-HCH, delta
      HCH, gamma-HCH), sigma DDT (p, p'-DDE, p, p'-DDD, o,p'-DDT, p, p'-DDT) and sigma
      Cyclodiene (Heptachlor, Aldrin, Heptachlor epoxide, Dieldrin, Endrin) ranged from
      2.42 to 7.95, 0.14 to 5.12, 0.55 to 6.01 ng g(-1), respectively. The most
      dominant pollutant among the OCPs was gamma-HCH with the concentration of 3.4
      (0.77 to 7.21) ng g(-1). Total PCB concentrations ranged between 0.59 and 15.93
      ng g(-1). Low chlorinated biphenyls (tri- and tetra-) dominated in total PCBs.
      Positive correlations were observed between the EDDT, sigma Cyclodiene, sigma OCP
      or sigma PCB and TOC of the sediments (P < 0.05, n = 10). No obvious correlation
      was observed between the sigma HCH and the TOC of the sediments.

PMID- 18610794
TI  - Evaluation of ethanol washing on dioxins-polluted soil and sediment based on
      adsorption relationships.
AB  - Multi-stage ethanol washing on dioxins-polluted soil and sediment were performed.
      The results indicated the existence of limit washing concentration (LWC), where
      no more dioxins were removed from the soil or the sediment by further washing. In
      each stage, dioxins concentration in the soil, sediment and ethanol could be
      described satisfactory by the Freundlich equation. The Freundlich capacity
      factor, K(ef) correlated with the LWC which was estimated to be ca. 1000 pmol g(
      1) in the case of soil, and about 150 pmol g(-1) in the case of sediment. Organic
      contents in the soil and sediment affected the Freundlich intensity parameter, n(
      1) but not K(f). A model, which enables the calculation of removal efficiency of
      PCDD/DFs at each stage using K(f), n, and initial PCDD/DFs concentration, is
      presented.

PMID- 18610793
TI  - Removal of endocrine disrupting compounds during conventional wastewater
      treatment.
AB  - There is evidence that aquatic organisms downstream of some sewage treatment
      works show endocrine disruption as a result of exposure to substances in the
      effluent. As a result, the Environment Agency of England and Wales, in
      collaboration with the UK Government and the water industry, has started an
      intensive programme to determine the fate and behaviour of endocrine disrupting
      compounds in sewage treatment works. Sampling sites for the endocrine disruption
      demonstration programme are located throughout England and Wales. This paper
      presents data from Nuneaton sewage treatment works (Warwickshire, England), a
      modem nitrifying activated sludge plant serving an equivalent population of
      98,000 and one of the selected sites for the demonstration programme. Results for
      the 24-hour survey carried out in June 2006 in which manual grab samples were
      taken hourly show excellent removal of estrone, estradiol, nonyl-phenol and the
      nonylphenolethoxylates (3-5 EO units) at 97, 99, 94 and 98% respectively. They
      also show excellent removal (99%) of estrogenicity, measured by the YES bioassay.
      However the removal of ethynylestradiol was poor at only 3%. In November 2006, a
      further survey was carried out comprising grab samples taken at 4-hourly
      intervals across a continuous 7-day period. This monitoring confirmed the good
      removal of estrone and estradiol, at 97.8% and 96.3% respectively as well as an
      excellent reduction in estrogenicity (98.3%), but again showed poor removal of
      ethynylestradiol of 5.6%. There was evidence of a diurnal pattern for estrone and
      estradiol concentrations and to a lesser extent for ethynylestradiol in samples
      of crude sewage with works returns. Peak concentrations tended to occur at around
      midday.

PMID- 18610795
TI  - Removal of tetracycline and sulfonamide classes of antibiotic compound by
      powdered activated carbon.
AB  - Removal of sulfonamide (SAs) and tetracycline (TAs) classes of antibiotic
      compound from deionized water and DOC water by powdered activated carbon (PAC)
      adsorption was evaluated in this study. According to the study results, TAs were
      more easily adsorbed than SAs although TAs were more hydrophilic than SAs. The
      phenolic compounds in TAs might be responsible for their high adsorption. Complex
      formation of TAs with metal and metal oxide on the surface of activated carbon
      might also contribute to higher adsorption. The hydrophobic effect was important
      for removal of SAs. More hydrophobic SAs were removed more easily. The carbon
      type was not important for adsorption of SAs and TAs. Coal based carbon and
      coconut based carbon showed similar removal efficiencies for these antibiotics.
      Dissolved organic materials interfered with adsorption of SAs and TAs. Organic
      interference was more significant for the antibiotic compound, which was more
      subject to the PAC adsorption. Self-decomposition of SAs and TAs occurred even
      after 1 day. TAs were more subject to self-decomposition than SAs. Depending on
      the antibiotic type, more than 60% of TA was removed through self-decomposition.

PMID- 18610796
TI  - Partition of six phthalic acid esters in soluble and solid residual fractions of
      wastewater sludges.
AB  - Distributions of six priority controlled Phthalic acid esters (PAEs), including
      di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP),
      benzyl butyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP), di-octyl
      phthalate (DOP) were studied based on soluble and insoluble fractions of sludge
      samples collected at four wastewater treatment plants in Shanghai, China. Three
      sludge samples comprised hydrophilic colloidal particles of high protein contents
      and low aromaticity. Meanwhile, these sludges contained DBP of 4.2 to
      approximately 5.7 mg kg(-1) dried solids (ds) and DEHP of 21.1 to approximately
      55.6 mg kg(-1) ds, respectively. Another sludge sample comprised mainly
      hydrophobic colloidal particles of humic substances and high aromaticity. It
      contained DBP of 1.18 mg kg(-1) ds and DEHP of 2.89 mg kg(-1) ds, respectively.
      The most abundant components noted amongst the six studied PAEs were DBP and
      DEHP, which mostly associated with the insoluble fraction of sludge.
      Specifically, the DBP and DEHP in insoluble fraction (the solid residual phase)
      accounted for 89.8 to approximately 98.2% and 88.6 to approximately 99.6% of
      those in the whole sludge. The partition coefficients of DBP and DEHP for the
      soluble and insoluble fractions of sludge correlated with the suspension SUVA254,
      suggesting that interaction between pi-electrons of DBP or DEHP and those of
      organic particulates in suspension contributes most of the sorption processes.

PMID- 18610797
TI  - Removal of hydrophobic micro-organic pollutants from municipal wastewater
      treatment plant effluents by sorption onto synthetic polymeric adsorbents: upflow
      column experiments.
AB  - Continuous upflow bench-scale column experiments were carried out to investigate
      the use of a synthetic form polymer, polypropylene, and polypropylene coated with
      a thin layer of n-hexane as sorbents for hydrophobic organic compounds present in
      the effluent of municipal wastewater treatment plant. Two polycyclic aromatic
      hydrocarbons, namely, phenanthrene and fluorene, were selected as representative
      hydrophobic organic compounds for experimental purposes. The effect of flow rate,
      column diameter and column height on the removal efficiency of polycyclic
      aromatic hydrocarbons was investigated. Removal efficiency was found to correlate
      well with hydraulic retention time, showing that retention time is the primary
      parameter in the design of the adsorption column. Dissolved organic matter did
      not sorb onto polypropylene or polypropylene coated n-hexane, and the presence of
      dissolved organic matter in the aqueous phase did not significantly affect
      sorption of polycyclic aromatic hydrocarbons. For experiments with polypropylene
      coated with n-hexane, an insignificant amount of n-hexane (less than 0.03 times
      the aqueous solubility of n-hexane in water) was lost due to dissolution in the
      effluent. The potential use of polypropylene coated n-hexane in upflow column
      experiments for the removal of hydrophobic organic compounds from the effluent of
      municipal wastewater treatment plants was demonstrated.

PMID- 18610799
TI  - An alien legend with a bite.

PMID- 18610798
TI  - Neuroprotective trials: no longer a cautious optimism.

PMID- 18610800
TI  - Special focus: allergy & asthma--introduction.

PMID- 18610801
TI  - Childhood asthma and obesity.

PMID- 18610802
TI  - Inner city asthma.

PMID- 18610803
TI  - The National Asthma Education and Prevention Program (NAEPP) guidelines: will
      they improve the quality of care in America?

PMID- 18610804
TI  - Update on stinging insect allergy.

PMID- 18610805
TI  - The role of pollens in allergy.

PMID- 18610806
TI  - Latex allergy.

PMID- 18610807
TI  - Advances in therapeutic immunomodulation of IgE-mediated respiratory disease.
AB  - IgE is responsible for activation of allergic reactions and is important to the
      pathogenesis of allergic diseases and the development and persistence of airway
      inflammation. Clinical evidence strongly supports the efficacy and safety of SLIT
      for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma
      and stinging insect hypersensitivity. Practice parameters help to guide the use
      of immunotherapy in conjunction with other pharmacologic and nonpharmacologic
      approaches. Allergy immunotherapy should be considered in patients with poor
      symptom control or adverse effects resulting from medications. In the US,
      subcutaneous immunotherapy remains the preferred form of immunotherapy. Its major
      advantages over sublingual immunotherapy appear to be efficacy and FDA approval,
      whereas SLIT seems to hold the promise of being safer and more convenient. If
      clinical trials with SLIT prove successful, an FDA-approved formulation will
      expand treatment choices; but for now, SLIT should be considered investigational.
      Whereas immunotherapy was first introduced over one century ago, the monoclonal
      anti-IgE antibody, omalizumab was introduced in 2004. Omalizumab works by
      nonspecifically inhibiting the IgE-mediated inflammatory cascade before it
      starts. FDA approval is currently limited to adults and adolescents (aged > or =
      12 years) with moderate-to-severe persistent allergic asthma. Omalizumab's
      expense can limit patients' access. Access to care is critical if the goals of
      the EPR-3 Asthma Guidelines are to be met. The Rhode Island Department of Health,
      in collaboration with community programs, the health care community, and policy
      makers produced The Asthma Control State Plan 2003-2008. With support by the
      State and other agencies, together with the implementation of the comprehensive
      management approach outlined in the EPR-3 Asthma Guidelines, there is good reason
      for hope that in Rhode Island, our most severe asthma patients will achieve
      control of their disease with reduction in asthma risk, morbidity and mortality.

PMID- 18610808
TI  - MR imaging of acute appendicitis in pregnancy.

PMID- 18610809
TI  - Case presentation: Mr. J, an 88 year-old man found on the floor, complaining of
      generalized weakness.

PMID- 18610810
TI  - Hospitalizations and associated costs for principal versus additional diagnoses
      of asthma: implications for monitoring children's health.

PMID- 18610811
TI  - Managing the unmanageable: elderly Russian Jewish emigres and the biomedical
      culture of diabetes care.
AB  - In this article, we examine the apparent resistance of elderly Russian Jewish
      emigres to the dominant U.S. biomedical model of diabetes treatment. Cultural
      competence on the part of medical professionals who make assumptions about
      Russian culture tends to be based on particularly American values of self-control
      and individual agency. The American consumer model of health care incorporating
      risk, individual responsibility, autonomy, and choice, when applied to elderly
      Russian Jewish emigres, results in a reading of different values and choices as
      failed self-management or noncompliance. This article argues for a more reflexive
      understanding of U.S. biomedical culture as a replacement for the current "sound
      bite" model of cultural diversity.

PMID- 18610812
TI  - Race, ethnicity, and racism in medical anthropology, 1977-2002.
AB  - Researchers across the health sciences are engaged in a vigorous debate over the
      role that the concepts of "race" and "ethnicity" play in health research and
      clinical practice. Here we contribute to that debate by examining how the
      concepts of race, ethnicity, and racism are used in medical-anthropological
      research. We present a content analysis of Medical Anthropology and Medical
      Anthropology Quarterly, based on a systematic random sample of empirical research
      articles (n = 283) published in these journals from 1977 to 2002. We identify
      both differences and similarities in the use of race, ethnicity, and racism
      concepts in medical anthropology and neighboring disciplines, and we offer
      recommendations for ways that medical anthropologists can contribute to the
      broader debate over racial and ethnic inequalities in health.

PMID- 18610813
TI  - The emergence of integrative medicine in Australia: the growing interest of
      biomedicine and nursing in complementary medicine in a southern developed
      society.
AB  - In this article, I examine the process by which some biomedical physicians and
      nurses in Australia have come to adopt various alternative therapies in their
      regimens of practice, largely in response to (1) the growing interest on the part
      of many Australians in what is generally called "complementary medicine", and (2)
      a recognition that biomedicine is not particularly effective in treating an array
      of chronic ailments. Some Australian biomedical physicians and nurses have come
      to embrace "integrative medicine," which purports to blend the best of
      biomedicine and complementary medicine, and have even created an Australasian
      Integrative Medical Association and established integrative medical training
      programs and centers. I argue that the adoption of alternative therapies and the
      development of integrative medicine on the part of Australian biomedical
      physicians and nurses constitute another national manifestation of the co-option
      of complementary and alternative medicine.

PMID- 18610814
TI  - Dying under the bird's shadow: narrative representations of degedege and child
      survival among the Zaramo of Tanzania.
AB  - In this article, I examine the cultural interpretations of degedege, an
      indigenous illness commonly recognized by the Zaramo people of coastal Tanzania
      as life threatening. Drawing on the narratives of three bereaved parents who lost
      a child to degedege, I analyze the contextual and circumstantial factors involved
      in these parents' negotiation of the identity of an illness and in their
      subsequent therapy seeking behavior. I show that even though cultural knowledge
      and etiological beliefs about degedege may be shared locally, there is
      significant variation in the therapeutic pathways that parents follow to deal
      with an actual episode of the illness. I emphasize the need for more
      contextualized data on health-seeking behaviors, and argue that it is necessary
      to pay attention to the micropolitics of health care decision making at the
      household level. Finally, I also call attention to the politics of provider
      patient communication at public health facilities as a means to improve public
      health interventions to increase child survival.

PMID- 18610815
TI  - The life and death of a street boy in East Africa: everyday violence in the time
      of AIDS.
AB  - This article focuses on the life history of a single street boy in northwestern
      Tanzania, whom I name Juma. I suggest that Juma's experiences and the life
      trajectory of himself and of significant individuals around him (particularly his
      mother) were structured by everyday violence. I describe everyday violence in
      terms of a conjuncture between macrostructural forces in East Africa (including a
      history of failed development schemes and the contemporary political economy of
      neoliberalism) and the lived experience of individuals as they negotiate local,
      contextual factors (including land-tenure practices, the power dynamics between
      immediate and extended kin, life on the streets, and constructions of gender and
      sexuality). I suggest that AIDS and its many impacts on Juma's life course can
      only be understood in a broader context of everyday violence. From this basis, I
      draw several general conclusions regarding AIDS prevention and intervention
      strategies.

PMID- 18610816
TI  - Our nation's immigrants in peril: an urgent call to social workers.

PMID- 18610817
TI  - Development of a family intervention for Native Hawaiian women with cancer: a
      pilot study.
AB  - Native Hawaiian women have high cancer rates and low survival rates. As with
      other women, a major source of support for Native Hawaiian women is their
      families. This pilot study reports on the feasibility of providing and measuring
      a culturally appropriate intervention designed to help Native Hawaiian women and
      their families deal with cancer. The feasibility evaluation indicated that a
      major strength of the intervention was its incorporation of Hawaiian values and
      practices, and a major limitation reflected the difficulties in recruiting Native
      Hawaiians for research studies. Despite the small sample size, the six Native
      Hawaiian women and their 10 family members in the intervention group showed
      improved self-efficacy and coping when compared with the four Native Hawaiian
      women and their eight family members in the control group. Pilot study data
      established the feasibility and potential effectiveness of this culturally
      tailored intervention for Native Hawaiians, and feasibility findings will be
      useful in designing follow-up studies. Steps taken to incorporate cultural values
      into an intervention also provide a model for other social workers in developing
      culturally appropriate interventions for minority populations.

PMID- 18610818
TI  - Suicidal ideation and attempts among sexual minority youths receiving social
      services.
AB  - The increased risk of suicidal ideation and attempts among sexual minority youths
      have been documented in studies using both convenience samples and representative
      community samples. However, as most youths do not access social services, these
      studies do not necessarily represent the sexual minority youths that community
      based social workers may encounter in their day-to-day practice. As such, the
      present study on risk and protective factors related to suicidality surveyed 182
      sexual minority youths (14 to 21 years of age) who sought assistance at a
      community-based social services agency in Denver. Similar to existing literature,
      the findings suggest that risk factors related to suicidality include
      hopelessness, methamphetamine use, homelessness, and in-school victimization.
      However, unlike studies of the general youth population, this study found that
      African American and male sexual minority youths were not at a lower risk of
      suicidality than sexual minority youths who were, respectively, white or female.
      In addition, our findings suggest that the presence of gay-straight alliances in
      schools may function as a protective resource for sexual minority youths.
      Implications for social work practice are discussed.

PMID- 18610819
TI  - Moving toward culturally competent practice with Muslims: modifying cognitive
      therapy with Islamic tenets.
AB  - Relatively little information exists on the provision of culturally competent
      services to Muslims, in spite of the growing presence of this population in the
      United States. Consequently, the authors discuss a number of therapeutic
      approaches in light of their level of congruence with common Islamic values.
      Psychodynamic approaches, for example, may not be as congruent as cognitive
      approaches. Although cognitive therapy may be relatively consistent with Islamic
      values, the self-statements that are central to this modality are often packaged
      in secular terminology that is inconsistent with Islamic norms. To provide
      culturally relevant services, practitioners must unwrap the secular terminology
      used to express the underlying therapeutic precepts and then repackage the
      precepts in terminology that reflects Islamic teaching. The authors conclude by
      offering a number of examples to illustrate the construction of statements that
      reflect Islamic values.

PMID- 18610820
TI  - Kin networks and poverty among African Americans: past and present.
AB  - Trends in social welfare policy and programs place increasing expectations on
      families to provide members with various forms of material and socioemotional
      support. The historic ability of kin networks of many African Americans to
      provide such support has been compromised by long-term community and family
      poverty. The potential mismatch between the expectations of social welfare
      systems for kin support and the actual functional capacities of kin networks
      places African Americans living in poverty at great risk of chronic poverty and
      its long-term multiple consequences. This article reviews historical and
      contemporary research on the structure and function of African American kin
      networks. On the basis of evidence of functional decline, the authors argue that
      social workers must re-examine the a priori assumption of viable kin networks as
      a reliable source of resilience among African Americans living in poverty. Social
      workers must focus assessment at all levels of practice on a variety of aspects
      of kin networks to make accurate judgments about not only the availability of
      resources, but also the perceived costs and benefits of participation in exchange
      for resources.

PMID- 18610821
TI  - Acting on our values: do social workers volunteer?
AB  - Volunteer activity among social workers is explored in this article. Anecdotal
      evidence suggests social workers are not major contributors of volunteer time.
      The overriding research questions of this descriptive-exploratory study are to
      what extent do social workers engage in volunteer activities, what factors
      influence their decisions to volunteer, and what are the types of activities in
      which they engage. Volunteerism is defined as giving of one's talent, time, and
      energy to individuals, groups, communities, or organizations without
      compensation. A 27-item survey specific to this study was devised. Mailing lists
      were procured from state licensing boards representing two states in each of 10
      federal regions. Random sampling was used to proportionally sample 5 percent of
      approximately 77,000 licensed social workers; useable surveys numbered 1,544 from
      a sampling pool of 3,850, yielding a 40 percent response rate. The findings
      demonstrate that social workers have volunteered in the past but no longer choose
      to do so. Respondents believe that other people should give and volunteer but
      that social workers give enough through their poorly paid jobs and poor working
      conditions. Implications suggest that the very professionals who might serve as
      community role models potentially have the reverse influence in regard to
      promoting volunteerism.

PMID- 18610822
TI  - The person-in-environment approach: professional ideology and practice of social
      workers in Israel.
AB  - The aim of this study was to explore the extent to which the person-in
      environment approach is part of the professional ideology of social workers in
      Israel and the degree to which they actualize it in their professional practice.
      The study examines the perceived importance of various goals of the social work
      profession and the perceived fittingness of diverse social work activities,
      actual professional activities, practice levels, and perceived attainment of
      social work goals. Based on the responses of 400 social workers from a wide
      variety of social services agencies in Israel, the results indicate that
      ideologically, the workers place a dual focus on the individual and society, with
      focus on the individual somewhat stronger. However, in practice the social
      dimension is marginal and the person-in-environment approach is hardly evident.

PMID- 18610823
TI  - Race and hospital diagnoses of schizophrenia and mood disorders.
AB  - Overdiagnosis or misdiagnosis of schizophrenia among African American clients is
      a longstanding and critical disparity in mental health services. Overdiagnosis of
      schizophrenia is detrimental because it increases the potential for treatment
      with the wrong medications. Inadequate assessment of mood disorders, co-occurring
      substance abuse, and client characteristics are three factors believed to be
      associated with the overdiagnosis of schizophrenia. This article examines the
      relationships among demographic characteristics, co-occurring substance abuse,
      and admission diagnoses of schizophrenia and mood disorder for clients admitted
      to state psychiatric hospitals in Indiana. Data were obtained from the state
      management information system for a sample of 2,404 clients. The sample comprised
      white clients (80.5 percent) and African American clients (19.5 percent). All but
      a few of the clients were involuntarily hospitalized, and more than half of them
      had a diagnosis of schizophrenia. African American clients were less frequently
      diagnosed with bipolar and major depressive disorders and more frequently
      diagnosed with schizophrenia than were white clients. After controlling for the
      influence of other demographic variables, client race was the strongest predictor
      of admission diagnoses of schizophrenia. Implications for social work practice in
      the field of mental health and mental health services research are discussed.

PMID- 18610824
TI  - Mental health in college athletics: it's time for social work to get in the game.

PMID- 18610825
TI  - From ideological to competency-based: the rebranding and maintaining of medical
      social work's identity.

PMID- 18610826
TI  - Frances Kellor and the Americanization movement.

PMID- 18610827
TI  - [DNA methylation in cotton hybrids and their parents].
AB  - The possible role of methylation in the performance of heterosis has been
      analyzed in many crops. To further study this possibility, we investigated both
      the differences in cytosine methylation patterns between cotton heterotic
      hybrid/nonheterotic hybrids and their parental lines and the change in
      methylation level from seedling stage to flowering stage by using the methylation
      sensitive amplified polymorphism (MSAP) method. The results showed that the
      number of demethylation loci in highly heterotic hybrids was greater that in
      lowly heterotic hybrids, and the level of DNA cytosine methylation in cotton at
      the seedling stage is higher than that at the flowering stage. The altered
      methylation patterns at low-copy genomic regions can be confirmed by DNA gel blot
      analysis. A total of 39 fragments that showed different methylation patterns were
      cloned and sequenced. The methylation status of these genes was modified
      differentially in hybrid and parents, suggesting that these genes might play a
      role in the performance of heterosis.

PMID- 18610828
TI  - [Isolation of a novel fructose-1,6-bisphosphate aldolase gene from Codonopsis
      lanceolata and analysis of the response of this gene to abiotic stresses].
AB  - A cDNA clone containing a fructose-1,6-bisphosphate aldolase (ALD) gene,
      designated ClAldC, was isolated from a medicinal plant Codonopsis lanceolata.
      ClAldC is predicted to encode a precursor protein of 358 amino acid residues, and
      its sequence shares high degrees of homology with a number of other ALDs. The
      expression of ClAldC in different C. lanceolata organs was analyzed using reverse
      transcriptase (RT)-PCR. The results showed that ClAldC expressed high in stems of
      intact plant, while expressed at low level in leaves and roots. In addition, the
      expression of ClAldC under different abiotic stresses was analyzed at different
      time points. Three tested abiotic stimuli, anoxygenic stress, hydrogen peroxide
      and chilling, triggered a significant induction of ClAldC within 2-8 h post
      treatment. However, there was no induction under other four stresses, NaCI,
      wounding, light and dark. The positive responses of ClAldC to the three abiotic
      stimuli suggested that C. lanceolata ClAldC may help to protect against
      environmental stresses such as anoxia, chilling and oxidative stress.

PMID- 18610829
TI  - [Genetic polymorphism in GST, NAT2, and MTRR and susceptibility to childhood
      acute leukemia].
AB  - It is known that presence of xenobiotic-metabolizing gene polymorphisms in some
      cases correlates with hereditary predisposition to the oncological diseases. In
      the present work the frequencies of xenobiotic-metabolizing gene polymorphisms in
      332 children with the diagnosis acute lymphoblastic leukemia (ALL), 71 children
      with the diagnosis acute myeloblastic leukemia (AML) and 490 healthy donors have
      been determined using allele-specific hybridization on the biochip. Statistically
      significant increase in the frequency of GSTT1 "null" genotype (OR = 1.9, p =
      4.7E-5) and GSTT1/GSTM1 double "null" genotype (OR = 3.1, p = 2.5E-8) in children
      with acute leukemia relative to healthy donors group has been revealed. Also 1.8
      fold increase in the frequency of NAT2 genotype 341T/T, 481C/C, 590G/G in
      children with acute leukemia relative to healthy donors group (p = 0.026) has
      been recognized. Analysis of gene-gene interactions has showed that in patients
      with acute leukemia genotype NAT2 341T/T, 481C/C, 590G/G in combination with
      GSTT1 "null" and/or GSTM1 "null" genotype is significantly more frequent than in
      population control. Besides the reduction of MTRR genotype 66G/G frequency in
      girls with acute leukemia relative to female healthy donors has been found (OR =
      0.50, p = 0.0015). Analysis of gene-gene interactions has shown that the presence
      of GSTT1 "null" and/or GSTM1 "null" genotype in combination with MTRR genotype
      66A/- may consider as risk factor of acute leukemia in girls. Thus, the studied
      polymorphic variants of genes GSTT1, GSTM1, NAT2 and MTRR can modulate the risk
      of childhood acute leukemia, residents of European part of Russia.

PMID- 18610830
TI  - [The origin of Yakuts: analysis of Y-chromosome haplotypes].
AB  - Gene pool structure of Sakha Republic (Yakutia) native population has been
      studied: we defined composition and frequencies of Y-chromosome haplogroups for
      Yakuts. Six haplogroups: C3 x M77, C3c, N*, N2, N3a and R1a1 have been revealed
      in Yakut gene pool. A greater part of Y-chromosome in Yakut population belongs to
      N3a haplogroup (89%). All investigated Yakut population samples have low values
      of gene diversity, calculated based on haplogroup frequencies. Gene
      differentiation of the investigated samples estimated using the analysis of
      molecular variance (AMOVA) by two marker systems (haplogroup frequencies and
      microsatellite haplotypes of Y-chromosome) revealed a portion of interpopulation
      differences amounting to 0.24 and 2.85%, respectively. Frequencies and molecular
      phylogeny of YSTR-haplotypes were revealed for N3a haplogroup of Y-chromosome.
      Altogether forty haplotypes were found in Yakuts. Evenks and Yakuts are
      characterized by overlapping and very specific spectrum of N3a haplotypes, which
      is not typical for other Siberian ethnic groups. Cluster analysis of populations
      by N3a YSTR-haplotypes shows Yakut isolation from Turkic-speaking populations in
      the South Siberia. Genetic diversity generation time for a specific spectrum of
      Yakut haplotypes was estimated as 4.45 +/- 1.96 thousand years. As opposed to the
      data on mtDNA, the obtained results give an evidence for significant contribution
      of a local palaeolithic component into Y-chromosomal Yakut gene pool.
      Ethnogenetic reconstruction of the present picture of genetic diversity in N3a
      haplogroup in the territory of Siberia is under consideration.

PMID- 18610831
TI  - [Genetics factors determining predisposition to chronic course of virus hepatitis
      and fibrosis in liver].
AB  - Polymorphic variants of several genes IL4 C(-590)T, IL4RA Ile50Val, TNF G(-308)A
      were studied for their association with extent of the disease chronization which
      is marked by hepatic fibrosis stage. Gradual decrease in A allele frequency of
      polymorphic marker G(-308)A in TNF gene, from patients with weak fibrosis to
      patients with cirrhosis. Group of patients with weak fibrosis was characterized
      by higher frequency of A allele (24.5%) comparing with patients with moderate and
      pronounced fibrosis (13.4%) and cirrhosis (8.7%). Differences in heterozygous
      genotype frequencies of IL4 C(-590)T were found between patients with cirrhosis
      (68.2%) and groups of patients with moderate and marked fibrosis (39.1%).

PMID- 18610832
TI  - [Association of immune system gene polymorphisms with quantitative features which
      are pathogenetically important in chronic viral hepatitis].
AB  - Association study was performed for genetic polymorphisms IL4 C(-590)T, IL4RA
      Ile50Val, TNF G(-308)A, to estimate their effect on quantitative features which
      are pathogenetically important for chronic viral hepatitis course, i.e. levels of
      IL4, IL10, IL12, tumor necrosis factor alpha, fibronectin, collagenase, protease
      inhibitors, macroglobulines, elastases, free and protein-bound hydroxyproline. It
      has been shown that A allele of TNF G(-308)A polymorphism is associated with
      decreased TNF-alpha, increased IL4 and IL12, as well as with low level of protein
      bound hydroxyproline. In addition, association of CT genotype of IL4 C(-590)T
      polymorphism and high level of protein-bound hydroxyproline has been identified.

PMID- 18610833
TI  - [AlkB homologues in thermophilic bacteria of the genus Geobacillus].
AB  - Screening of alkane hydroxylase genes (alkB) was performed in the thermophilic
      aerobic bacteria of the genus Geobacillus. Total DNA was extracted from the
      biomass of 11 strains grown on the mixture of saturated C10-C20 hydrocarbons, PCR
      amplification of fragments of alkB genes was performed with degenerate
      oligonucleotide primers, PCR products were cloned and sequenced. For the first
      time in the genome of thermophilic bacteria the presence of a set of alkB gene
      homologues was revealed. The strains each contain three to six homologues among
      which only two are universal for all of the strains. Comparative phylogenetic
      analysis of the nucleotide sequences and the inferred amino acid sequences showed
      close relatedness of six of the revealed variants of geobacilli sequences to the
      alkB4, alkB3, and alkB2 genes that had previously been revealed by other authors
      in Rhodococcus erythropolis strains NRRL B-16531 and Q15. The rest two variants
      of alkB sequences were unique. Analysis of the GC composition of all the
      Geobacillus alkB homologues revealed closer proximity to the rhodococcal
      chromosomal DNA than to the chromosomal DNA of geobacilli. This may be an
      indication of the introduction of the alkB genes into the Geobacillus genome by
      interspecies horizontal transfer; and rhodococci or other representatives of the
      Actinobacteria phylum were probably the donors of these genes. Analysis of the
      codon usage in fragments of alkB genes confirms the suggestion that the pool of
      these genes is common to the majority of Gram-positive and certain Gram-negative
      bacteria. Formation of a set of several alkB homologues in a genome of a
      particular microorganism may result from free gene exchange within this pool.

PMID- 18610834
TI  - [Inhibition of calpain expression by E-64d in the rat retina subjected to
      ischemia/reperfusion injury].
AB  - To investigate the effect of E-64d, a selective inhibitor of calpain, on the
      expression of calpain and calpastatin in rat retina subject to
      ischemia/reperfusion injury (IRI). An animal model of retinal IRI was set up by
      increasing the intraocular pressure (110 mmHg) of a rat eye for 1 h. The retinal
      thickness and morphologic changes were detected by histology. The protein
      expression of m-calpain (a calpain isoform) in the retina was assessed by
      immunohistochemistry and Western blot assay. The mRNA of m-calpain as well as
      calpastatin (an endogenous protein inhibitor of calpain) in the retina was
      assessed by RT-PCR, and the ratio of m-calpain/calpastatin was then calculated.
      To evaluate the effect of E-64d on the expression of calpain, the drug (5 microl
      of 100 microM) was injected intravitreously immediately after IRI. There were
      retinal edematous changes, particularly in the inner plexiform layer after IRI.
      The protein expression of m-calpain in the retina was increased 24h after IRI, an
      effect that was inhibited by E-64d (P < 0.05). The mRNA expression of m-calpain
      and calpastatin was also increased 24 h and 3 h after IRI, respectively. Neither
      m-calpain nor calpastatin mRNA expression was influenced by E-64d (P > 0.05). The
      mRNA ratio of m-calpain to calpastatin was increased at the 6 h, 24 h and 72 h
      after IRI, and only at 24 h the increase of the ratio of m-calpain to calpastatin
      was inhibited by E-64d (P < 0.05). In the rat retina of IRI, E-64d inhibits the
      increase of m-calpain protein expression, as well as the mRNA ratio increase of m
      calpain to calpastatin. E-64d also inhibited the retinal damage induced by IRI,
      suggesting a role for E-64d in the protection of the retinal apoptosis induced by
      IRI.

PMID- 18610835
TI  - [Molecular identification and expression of heat shock cognate 70 (HSC70) in the
      Pacific white shrimp Litopenaeus vannamei].
AB  - Heat shock protein 70s (HSP70s) are fundamental chaperone proteins that are
      indispensable to most living organisms. In order to investigate the function of
      HSP70 and heat shock response in shrimp, a heat shock cognate (HSC70) gene of the
      white shrimp (Litopenaeus vannamei), containing a 1959-bp open reading frame, was
      cloned and characterized. The amino acid sequence, 71.5 kDa of molecular weight,
      shares 80-99.6% homology with 12 diverse species' HSP70s and HSC70s. In fact,
      some segments of the eukaryotic HSC70 sequence, such as ATP/GTP-binding site,
      cytoplasmic HSP70 C-terminal sequence, and GGMP/GAP repeats, are also found in
      the putative shrimp HSC70. Moreover, multi-tissue RT-PCR was performed to assay
      the basal expressions of HSC70 in the heart, gill, hepatopancreas, stomach, gut,
      and muscle. The results demonstrate that the basal expressions of HSC70 in theses
      organs are similar to that of beta-actin. Furthermore, quantitative real-time
      experiments showed that HSC70 was up-regulated in hepatopancreas (4.6-fold),
      stomach (5.9-fold), gut (2.6-fold), and muscle (3.5-fold) but not in the heart
      (1.7-fold) and gill (1.6-fold) after 2 h of heat shock. Nevertheless, the HSC70
      was found to be highly expressed in the heart and gill following 6 h of heat
      shock. This suggests that HSC70 in white shrimp possess both short-term and long
      term responses to heat shock stress, indicating this HSC70 may be a heat
      dependent HSC70 member. Finally, we constructed an expression vector to generate
      HSC70 in Escherichia coli BL21, which displayed immune cross-reactivity with
      mouse HSP70 antibody. In conclusion, the identification and expression of white
      shrimp HSC70 gene present useful data for studying the molecular mechanism of
      heat shock response and the effect of heat shock proteins in shrimps'
      cytoprotection.

PMID- 18610836
TI  - [Calcium-dependent mechanism of somatic embryogenesis in oncogene rolC expressing
      cell cultures of Panax ginseng].
AB  - It was shown earlier, that ginseng embryogenic cell culture 2c3 was obtained as a
      result of callus cells transformation with the Agrobacterium rhizogenes rolC
      oncogene. In the present report we determine that inhibitors of Ca2+-channels
      (LaCl3, verapamil, niflumic acid) certainly lowered the quantity of somatic
      embryos in the 2c3 cell culture. This is the evidence of the influence of calcium
      dependent signal system on plant embryogenesis. Protein kinases inhibitors W7 and
      H7 also caused the lowering of somatic embryos quantity in the 2c3 cell culture.
      We analysed changes of CDPK genes expression in embryogenic 2c3 cell culture.
      Total expression decreased 1.2-1.5 times comparing with the control callus
      culture. CDPK expression in the 2c3 embryogenic culture lowered by the inhibition
      of expression of the gene subfamilies PgCDPK1 (PgCDPK1a and PgCDPK1b) and PgCDPK3
      (PgCDPK3a). At the same time, expression of PgCDPK2 gene subfamily (PgCDPK2b and
      PgCDPK2d) was increased. We suppose that genes of PgCDPK2 subfamily might be
      responsible for the embryogenesis initiation in the 2c3 ginseng cell culture. It
      was shown for the first time that the rolC gene and the process of embryogenesis
      could change expression of particular forms of CDPK genes.

PMID- 18610837
TI  - [Telomeric oligonucleotide complexes with PGEk protein vector: internalization by
      target cells and antiproliferative properties].
AB  - The recombinant protein PGEk, containing residual of the human epidermal factor
      (hEGF) bearing DNA binding sequence, retains ability of hEGF to bind with hEGF
      receptor and to induce cell proliferation was shown. On an example of PGEk
      complexes with telomeric mimic-oligodeoxyribonucleotide d(TTAGGG)4 and with its
      thio-analogue we had found such systems can be effectively and selectively
      internalized by hEGF receptors super expressing cells. The association of this
      process with a protein/oligonucleotide ratio in complexes was investigated. The
      intracellular localization of oligonucleotides was explored. We had shown that
      PGEk not only promotes intensive delivery of oligonucleotides, but also protects
      them from degradation by nucleases. The oligonucleotides in composition of
      complexes have considerably more expressed cytotoxic activity in comparison with
      free oligonucleotides.

PMID- 18610838
TI  - [Ap1-like cis-elements in 5'-regulatory region of human apolipoprotein A-I gene].
AB  - Several Ap1-like cis-acting elements were found within 5'-regulatory region (
      2497...+173 versus transcription start point) of human apolipoprotein A-I gene
      (5'-apoA-I). Those elements are capable to interact with transcription factors
      belonging to Ap1 and CREB/ATF families. Those elements are localized outside of
      the hepatic enhancer (-220...-110) and the sequence responsible for apoA-I gene
      transcription in Caco2 cells (-595...-192). One of Ap1-like sites (5'-TGAGGTCT-3,
      Cre/jun2/apo) is present within 5'-apoA-I in two copies - distal (-1798 ...-1791)
      and proximal (+99...+106) ones. This and other Ap1-like sites - 5'-TGACTCT-3' (
      1798...-1791, PF1) and 5'-TGACATCA-3' (-1171...-1163, Cre/jun1) were
      characterized by EMSA. It was shown by using the specific antibodies to c-Jun and
      ATF2 transcription factors in EMSA supershift experiments, that the DNA-protein
      complexes formed by Cre/jun2/apo, Cre/jun1 elements with nuclear proteins of
      human hepatoma HepG2 cells contain ATF2. The functional role of 5'-apoA-I regions
      containing Ap1-like sites was studied in cotransfection experiments of HepG2
      cells (synthesize endogenous ApoA-I), human duodenum adenocarcinoma Hutu80 cells
      (do not synthesize endogenous ApoA-I), human neuroblastoma SK-N-SH cells (do not
      synthesize endogenous A-I) with expression vectors of c-jun and mekk1 genes. It
      was shown, that those Ap1-like sites appears to be responsible (the proximal
      Cre/jun2/apo is more efficient) for tissue-specific regulation of human apoA-I
      gene expression.

PMID- 18610839
TI  - [C-terminal fragment of ribosomal protein S15 is located at the decoding site of
      the human ribosome].
AB  - Protein S15 is a characteristic component of the mammalian 80S ribosome that
      neighbors mRNA codon at the decoding site and the downstream triplets. In this
      study we determined S15 protein fragments located close to mRNA positions +4 to
      +12 with respect to the first nucleotide of the P site codon on the human
      ribosome. For cross-linking to ribosomal protein S15, a set of mRNA was used that
      contained triplet UUU/UUC at the 5'-termini and a perfluorophenyl azide-modified
      uridine in position 3' of this triplet. The locations of mRNA analogues on the
      ribosome were governed by tRNAPhe cognate to the UUU/UUC triplet targeted to the
      P site. Cross-linked S15 protein was isolated from the irradiated with mild UV
      light complexes of 80S ribosomes with tRNAPhe and mRNA analogues with subsequent
      cleavage with CNBr that splits polypeptide chain after methionines. Analysis of
      modified oligopeptides resulted from the cleavage revealed that in all cases
      cross-linking site was located in C-terminal fragment 111-145 of protein S15
      indicating that this fragment is involved in formation of decoding site of the
      eukaryotic ribosome.

PMID- 18610840
TI  - [Interactions of human ribosomal protein S3 with undamaged and damaged DNA].
AB  - Human S3 protein (hS3) is a structural component of the ribosome, which, in
      addition to its role in translation, possesses activities typical of some DNA
      repair enzymes. Recombinant hS3 purified from inclusion bodies and refolded under
      different conditions was investigated for its ability to bind and cleave
      oligodeoxyribonucleotide substrates containing different lesions abundant in
      cellular DNA (apurine/apyrimidine sites, uracil, 8-oxoguanine, 8-oxoadenine, 5,6
      dihydrouracil, hypoxanthine). hS3 catalyzed cleavage of apurine/apyrimidine sites
      through beta-elimination mechanism forming a transient Schiff base covalent
      intermediate, but did not cleave substrates containing other lesions. Refolding
      of hS3 in the presence of Fe2+ and S2- ions did not increase its activity,
      despite the earlier suggestions that this protein could contain an iron-sulfur
      cluster. Binding of hS3 to DNA ligands containing oxidized and deaminated bases
      was less efficient than its binding to undamaged DNA. Therefore, the activity of
      hS3 on apurine/apyrimidine sites is not likely to be involved in the global in
      vivo DNA repair but could have a role in the repair in some specific locations in
      the genome.

PMID- 18610841
TI  - [Novel structural tree for beta-proteins containing abcd-units].
AB  - A database of 528 beta-proteins and beta-domains containing abcd-units (among
      them 244 are nonhomologous) has been compiled from the Protein Data Bank (total
      1511 PDB entries). A novel structural tree for this structural class of proteins
      that is composed of 153 possible polypeptide chain folds has been constructed.
      The structural classification of beta-proteins containing abcd-unit based on the
      structural tree has been developed. Both the database and the structural tree are
      accessible at the web-site (http://strees.protres.ru/).

PMID- 18610842
TI  - [The mechanisms of the proteolytic degradation of native globular proteins. The
      role of local and global fluctuations of the native structure].
AB  - Analysis of the proteolytic degradation of the native protein structure carried
      out by the comparison of the temperature dependence of the hydrogen exchange and
      proteolytic splitting rates of the hen egg-white lysozyme and human Hb and apoHb.
      Acceleration of the burst-like (all or none) proteolytic degradation in the high
      temperature range is provided by the intensification of the global fluctuations
      with overall unfolding revealed by hydrogen exchange. For Hb and apoHb the rate
      of burst-like proteolytic degradation and hydrogen exchange weakly depends on
      temperature in the range, where hydrogen exchange reveals only local fluctuations
      of the native protein structure. The splitting of the two proteins proceeds by
      the selfaccelerated burst-like mechanism with the initial rate-limiting single
      cleavage owing to the local fluctuation of the native structure. The local
      fluctuations play important role also upon the intracellular burst-like
      degradation of native proteins.

PMID- 18610843
TI  - [Molecular modeling of positioning of human release factor eRF1 relative to mRNA
      stop-codon explains a proximity of the eRF1 C-domain to stop-codon in ribosomal
      complex].
AB  - A properties of atomic models of structure of eukaryotic triple complex eRF1 .
      mRNA . tRNAPhe containing human class-1 polypeptide release factor eRF1 at the A
      site of human 80S ribosome, mRNA and P-site tRNAPhe, obtained before, are
      considered. The stricture of the complex is described using high resolution NMR
      structure of eRF1 M-domain. The structural properties of distribution of chemical
      cross-links are investigated, which allows us to choose correct model of
      positioning of the eRF1 molecule in ribosome A-site relative to stop codon of
      mRNA. A distributions of crosslinks between photoactivatable perfluoroaryl azide
      group of modified nucleotides of mRNA analogues and eRF1 molecule are modeled via
      molecular dynamics method. Twelve different mRNA analogues with modified
      nucleotides of stop signal in positions +4 to +9 with respect to the first
      nucleotide of the P-site codon are modeled. It was shown that only one of the two
      models of complex eRFI . mRNA . tRNA gives cross-link distribution in a good
      agreement with experimental data. A new features of the final structure of triple
      complex eRF1 . mRNA . tRNA is spatial proximity of stop-codon nucleotides to the
      C-domain of the eRF1, which explains previously obtained cross-link experimental
      data.

PMID- 18610844
TI  - [Changes of introns and exons length in genes of arabidopsis, rice, nematode and
      human].
AB  - Genes of Arabidopsis thaliana, Orysa sativa, Caenorhabditis elegans, Homo sapiens
      have been studied by computer analysis. The average intron and exon lengths in
      genes of these organisms decreases with increase of intron number in genes. The
      length of introns and exons in A. thaliana and O. sativa genes is change with
      increase of intron number in genes by high coefficient of correlation. Linear
      dependence between the sum of exon lengths and intron number in genes increased
      proportionally to number of gene introns. The average length of introns and genes
      of human depend on density of genes in DNA.

PMID- 18610845
TI  - [The SCAR DNA sequence family is enrichment in the evolution-conserved
      sequences].
AB  - Synaptonemal complex (SC) is a specific structure for prophase I of meiosis.
      Recently we have described synaptonemal complex tightly associated regions of DNA
      (SCARs DNA) as a particular family of genomic DNA. Now we reveal the evolutionary
      conservation of SCAR DNA sequences of vertebrates. This data correlates with
      universal morphology of SCs and similar processes proceed in prophase I of
      meiosis at representatives of different taxa.

PMID- 18610846
TI  - [Expression of foreign gene by cysteine proteinase null recombinant baculovirus].
AB  - The baculovirus expression vector systems (BEVS) are broadly used for producing
      foreign proteins in lepidopteran larvae. Most commercial BEVS are engineered to
      insert foreign genes into the polyhedrin (polh) locus and lack the polh gene.
      These viruses cannot produce occlusion bodies and are inconvenient for per os
      inoculation of larvae. Current knowledge in baculovirus genomics makes it
      possible to engineer BEVS into other parts of the virus genome. In our work, we
      have expressed recombinant M-HBsAg (middle surface antigen of human hepatitis B)
      in the baculovirus construct, rBmNPV-Deltav-cath-M-HBsAg, inserting foreign gene
      into the v-cath locus of the Bombyx mori nucleopolyhedrovirus (BmNPV) such that
      the v-cath gene is deleted and the native polh gene is retained. Silkworm larvae
      were infected per os and M-HBsAg was observed to be abundantly produced at a very
      late stage of infection.

PMID- 18610847
TI  - [Transcription levels of the MYCN gene in blood cell subpopulations of Patients
      with leukemia].

PMID- 18610848
TI  - [Pathomorphosis of rectal cancer after irradiation on the background of intra
      arterial regional chemotherapy].
AB  - In cancer recti patients, to whom intraarterial chemotherapy, using fluorouracil,
      was conducted, in the tumour parenchyma the dystrophic, necrobiotic and necrotic
      changes are prominent, resulting in the ulcer formation, the parenchyma/stroma
      ratio disturbance with the stroma prevalence, thickening and petrification foci
      establishment. As well, the lymphocytes and plasmocytes quantity in stroma is
      enhancing, witnessing the immune reactions activation. Under the influence of
      fluorouracil the plasmatic infiltration, hyalinosis and the arteriols lumen
      obliteration occur. The macrophages reaction, the large quantity of a giant
      multinuclear cells "foreign bodies" occurrence witness the nonviable state of the
      tumoral cells.

PMID- 18610849
TI  - [Reamberin application in the treatment of obturational jaundice of nontumoral
      etiology].
AB  - The influence of the preparation reamberin on endogenic intoxication severity in
      the patients, operated on for obturational jaundice of nontumoral etiology, was
      studied up. In 10 patients 1.5% solution of reamberin, infused continuously
      intravenously in 400 ml/day dosage during 3-10 days, was applied in complex
      postoperative therapy. It was established, that obturational jaundice of
      nontumoral etiology goes together with endogenic intoxication and the antioxidant
      defence system (ADS) inhibition. The preparation reamberin application had
      promoted more rapid normalization of the endotoxicosis and ADS indexes, comparing
      with such in controls.

PMID- 18610850
TI  - [Application of preparations--analogues of somatostatin in surgical
      pancreatology].
AB  - The experience of application of shortly acting and durably acting preparations-
      analogues of somatostatin in complex therapy of various pancreatic diseases was
      summarized. There was established similar efficacy of the preparations in
      blockade of the pancreatic external secretion and the various duration of their
      inhibiting influence on the blood flow. The trustworthy differences in the
      complications frequency and lethality while application of various preparations-
      analogues of somatostatin were not revealed.

PMID- 18610851
TI  - [Anesthesiological support during performance of endovascular prosthesis for the
      infrarenal aorta aneurysm].
AB  - The results of treatment of 10 patients, suffering the abdominal aorta aneurysm,
      using the third generation bifurcational prosthesis Excluder, are presented.
      Endoprosthesis was performed under local infiltrating anesthesia (LIA) and light
      sedation, in one observation the LIA was incidentally changed to general
      anesthesia and artificial lung ventilation. In the early postoperative period the
      complications did not occur. LIA may be successfully applied if the patient was
      thoroughly prepared and informed, the arteries were accurately dissected and
      intravascular apparatuses inserted, as well as the performance of the aorta
      endoprosthesis for the abdominal aorta aneurysm was not durable.

PMID- 18610852
TI  - [Remote results of surgical treatment of the patients with multilevel
      atherosclerotic damage of the main arteries of the lower extremity].
AB  - The results of treatment of 131 patients, suffering multilevel atherosclerotic
      affection of abdominal aorta and the main arteries of the lower extremity, are
      adduced. Algorhythm of arterial reconstruction performance depending on the
      spread of the aorto-iliac and femoro-politeal segments affection, was elaborated.
      There were applied two methods of treatment: reconstruction of aorto-iliac
      segment only and simultaneous reconstruction of arteries on two levels. The
      differentiated approach to performance of arterial reconstruction application
      have permitted to achieve positive result in 80% of patients in terms of 5-year
      follow-up. The lower extremity was secured in 83% of them, mortality had
      constituted 20%.

PMID- 18610853
TI  - [Mini-invasive operative interventions for spontaneous pneumothorax on the
      background of nonspecific pulmonary diseases].
AB  - The data, concerning the rate, causes and conditions of occurrence, localization
      of spontaneous pneumothorax, occurring on the background of non-specific
      pulmonary disease, tactic of its treatment, were adduced. The accent was done on
      the expediency of thoracoscopy performance for the correct diagnosis
      establishment as well as in the further tactic of treatment determination. The
      miniinvasive technologies introduction had permitted to improve the results of
      the patients treatment significantly and to prevent recurrence of spontaneous
      pneumothorax.

PMID- 18610854
TI  - [The methods of prophylaxis and treatment of an acute pulmonary injury in
      patients with traumatic disease complicated by enteral insufficiency syndrome].
AB  - The method of treatment of an acute pulmonary damage syndrome in the injured
      persons, suffering traumatic disease, complicated by enteral insufficiency
      syndrome, using preparation cytochrom C, was depicted. The results obtained
      witness the high clinical efficacy of the treatment scheme proposed.

PMID- 18610855
TI  - [Adrenergic reactivity and course of the wound process in diabetes mellitus
      condition: diagnostic significance and pathogenetic interpretation].
AB  - In order to establish interrelationship between the organism adrenoreactivity and
      the wound process course in presence of diabetes mellitus the dynamics of
      effective concentration of alpha2-adrenoreceptors agonist (alpha2-AR), causing
      aggregation of 50% of thrombocytes (EC50) in patients, suffering diabetes
      mellitus, complicated by purulent-necrotic affection of lower extremities in
      admission to the hospital and during the period of treatment, was studied. The
      cutaneous wounds healing was accompanied by the organism adrenoreactivity
      normalization, in condition of durable unhealing of the wound the alpha2-AR
      sensitivity tolerance to the therapy performed was noted. It permits to consider
      the EC50 index as a criterion of severity of dysregulation changes and the
      therapy efficacy.

PMID- 18610856
TI  - [Structure of injuries and the factors of traumatogenesis in catatrauma].
AB  - There are presented the data, obtained as a result of investigation of
      demographic indexes and traumatogenesis in catatrauma. Basing on the indexes, the
      main biomechanical factors, influencing clinical peculiarities of this contingent
      of the injured persons, were delineated.

PMID- 18610857
TI  - [Gastroduodenal ulcers in the practice of joint endoprosthesis].
AB  - The gastroduodenal ulcer rate and the gastrointestinal hemorrhage occurrence
      probability after total endoprosthesis of the hip and knee joint were studied. Of
      526 patients in 4 (0.7%) after the total joint endoprosthesis operation the
      gastroduodenal ulcer had occurred, demanding the urgent treatment measures
      conduction. It is mandatory to conduct an adequate prophylactic measures to the
      patients, suffering pronounced gastropathy, according to anamnestic data
      available.

PMID- 18610858
TI  - [Application of cryodestruction in the treatment of the bone giant cell tumor].
AB  - In 25 patients in the Division of tumors of the support-movement apparatus the
      osteoplastic operations were performed, using intraoperative cryodestruction,
      after excision of the giant cell tumor of the bone. During the patients
      observation follow-up postoperative complications, recurrences and metastases of
      the tumor were not revealed.

PMID- 18610859
TI  - [Using fixing devices "metost" in ostheosynthesis for prophylaxis of
      complications of the bones fractures].
AB  - The experience of developing, preclinical examinations and results of
      introduction to clinical practice of a new fixating device, owing original
      construction, of the "METOST" system was summarized.

PMID- 18610860
TI  - [Possibilities of plastic reconstructive surgery in the replacement of the
      defects of head and neck tissues. Part 2].

PMID- 18610861
TI  - [Surgical treatment of isolated echinococcosus of the pericardium].

PMID- 18610862
TI  - Feeling the health insurance squeeze.

PMID- 18610863
TI  - Promises, promises.

PMID- 18610864
TI  - It's the care that counts.

PMID- 18610865
TI  - Are we ready?

PMID- 18610866
TI  - Free sometimes costs.

PMID- 18610867
TI  - Can't we all just get along?

PMID- 18610868
TI  - "Texas Medicaid is going to have to do a lot better before I will see anyone in
      my office." Not convinced.

PMID- 18610869
TI  - Slightly better than nothing.

PMID- 18610870
TI  - Tort reform under attack.

PMID- 18610871
TI  - Prove your worth.

PMID- 18610872
TI  - So far, so good.

PMID- 18610873
TI  - Swipe it.

PMID- 18610875
TI  - Do you have financial staying power?

PMID- 18610874
TI  - Pattern of chlorine gas exposures reported to Texas poison control centers, 2000
      through 2005.
AB  - Exposure to chlorine gas can result in serious adverse effects including death.
      From 2000 through 2005, approximately 9000 chlorine gas exposures were reported
      annually to poison control centers in the United States. Because a review of the
      literature failed to produce any Texas-specific data concerning chlorine gas
      exposures, we conducted a retrospective review of Texas poison control center
      calls and found that 2643 calls related to human exposures to chlorine gas
      occurred during these 6 years. The number of these calls increased during this
      period. Of the exposures, 750% occurred at home and 65% occurred during the
      months of May through August. Inhalation was the primary mode of exposure. While
      most exposures resulted in no or minor affects, approximately one-fourth required
      that the affected person be seen at a health care facility. Preventive activities
      are needed to educate people about the potential dangers associated with products
      that contain chlorine.

PMID- 18610876
TI  - For HSAs, the time may be/could be/is now.

PMID- 18610877
TI  - Your practice--marketing on the internet.

PMID- 18610878
TI  - Obstructive sleep apnea: don't be asleep at the chair.

PMID- 18610879
TI  - Screening for obstructive sleep apnea in the dental office setting.
AB  - Obstructive sleep apnea (OSA) is a widespread disease with a prevalence of 4 to 9
      percent in the world's population. It occurs in all age groups from neonates to
      senior citizens, but weight, age, race and gender all influence its expression.
      OSA is as common as asthma and in its severe form can cause fatal cardiovascular
      damage. Since a dental practice often treats entire families on a routine basis,
      the setting is a natural place to aid in identifying patients at risk for having
      OSA.

PMID- 18610880
TI  - Patient-perceived anxiety levels associated with use of selective serotonin and
      serotonin norepinephrine reuptake inhibitors.
AB  - Dental practitioners are sometimes reluctant to treat patients who are on
      psychopharmacological agents, due perhaps to the belief that these patients will
      be difficult to deal with. However patients whose medical history indicates
      emotional and psychiatric disorders and who are being treated with SSRI or SSNRI
      agents may actually present a more positive and more receptive attitude to
      treatment than what was sometimes previously encountered in these same
      individuals.

PMID- 18610881
TI  - Communication: a case against underocclusion.
AB  - Hypo-occlusion is another term for underocclusion. This condition is often caused
      during crown-and-bridge procedures where an incorrect mounting of opposing dental
      casts, the injudicious polishing of the occlusal surface of a cast restoration,
      or the intended placement of an occlusal shim prior to the casting will guarantee
      a close occlusal contact--one that doesn't make contact. Hypo-occlusion may also
      take place during routine restorative work where the clinical operator "ditches"
      the restoration for assumed longevity. Implant specialists often advocate to the
      restorative dentist that their implants should be constructed with no lateral
      interferences and with a light centric contact or one that is just underocclusal
      contact. What exactly does this mean?

PMID- 18610882
TI  - A clinico-pathologic correlation. Sebaceous lymphadenoma.

PMID- 18610883
TI  - Transient lingual papillitis.

PMID- 18610884
TI  - Platform switching.

PMID- 18610885
TI  - The perfect alibi.

PMID- 18610886
TI  - The Texas Medicare manifesto.

PMID- 18610887
TI  - "They sat on our money".

PMID- 18610888
TI  - Round three.

PMID- 18610889
TI  - Workers' comp worth it?

PMID- 18610890
TI  - Avoid the 'roids.

PMID- 18610891
TI  - Detecting MRSA.

PMID- 18610892
TI  - Local doctor creates clothing with tourniquets for troops.

PMID- 18610893
TI  - [It is necessary to think and do].

PMID- 18610894
TI  - [Psychiatric nursing].

PMID- 18610895
TI  - [The future belongs to ambulatory psychiatric nurses].

PMID- 18610896
TI  - [Help for heavily traumatized people].

PMID- 18610897
TI  - ["Integration" instead of "confrontation".. Interview by Margrit Bachl].

PMID- 18610898
TI  - [Anxiety and stress as a fertile field for aggression].

PMID- 18610899
TI  - [Genetic history an introduction].

PMID- 18610900
TI  - [Importance of one's autonomy and individuality].

PMID- 18610901
TI  - ["People concerned with cancer care competency. Interview by Urs Luthi].

PMID- 18610903
TI  - [Correct conditions can be learned].

PMID- 18610902
TI  - [First script about bringing about changes].

PMID- 18610904
TI  - [Opening up modifications].

PMID- 18610905
TI  - [The future is for those who walk].

PMID- 18610906
TI  - [Ethnopsychiatry:: a field for change].

PMID- 18610907
TI  - [Living with bipolar disorders].

PMID- 18610908
TI  - [Evidence-based nursing, a response to the urgency of quality].

PMID- 18610909
TI  - [Infarction: a chance in the life of a couple].

PMID- 18610910
TI  - [Hormones contradict cliches].

PMID- 18610911
TI  - [Mobility: an opportunity for health promotion].

PMID- 18610912
TI  - Whenua--the key to Maori health and well-being.

PMID- 18610913
TI  - Accessing nursing workforce information.

PMID- 18610915
TI  - Closing the health gaps. Interview by Anne Manchester.

PMID- 18610916
TI  - Examining the impact of the inaugural MECA.

PMID- 18610917
TI  - Awakening from addiction the Maori way.

PMID- 18610918
TI  - Should non-Maori research and write about Maori?

PMID- 18610919
TI  - Helping patients quit smoking.

PMID- 18610920
TI  - Preparation for and practice in the nurse practitioner role.

PMID- 18610921
TI  - What is care--really?

PMID- 18610922
TI  - Te Rau Kokiri--an inspirational journey.

PMID- 18610923
TI  - Going the extra mile.

PMID- 18610924
TI  - TNA House of Delegates further clarifies a position on workplace.

PMID- 18610925
TI  - If the new pay system is fair, why are so many nurses on a downward slide?

PMID- 18610926
TI  - Breaking the chain.
AB  - The method of smoking cessation devised by the late Allen Carr has many devotees-
      and some detractors.

PMID- 18610927
TI  - Global mission.
AB  - Gretta Styles was internationally renowned as a nursing scholar. Since her death,
      her daughter has set up a foundation to help people in disease-burdened countries
      become nurses.

PMID- 18610928
TI  - Out of the shadows.

PMID- 18610929
TI  - Counting the cost.

PMID- 18610930
TI  - Working rights in the balance.

PMID- 18610931
TI  - Graduated compression stockings to prevent deep vein thrombosis.
AB  - This article describes the correct use and length of graduated elastic
      compression stockings to prevent deep vein thrombosis (DVT) in general surgical
      patients. The authors aim to establish whether above or below knee stockings are
      more effective in the prevention of DVTs, discuss anti-embolic prophylaxis and
      offer advice on the appropriate management of patients.

PMID- 18610932
TI  - Setting up and priming an intravenous infusion.
AB  - The setting up and priming of an intravenous infusion is a common nursing
      procedure. However, it is associated with certain complications, for example
      infection. This article describes a step-by-step guide to the equipment required,
      correct preparation of the patient and the procedure. It also provides readers
      with calculation of drip-rate formulae.

PMID- 18610933
TI  - Primary breast cancer: risk factors, diagnosis and management.
AB  - This article focuses on the risk factors, diagnosis and management of primary
      breast cancer. It describes the treatments that may be offered to patients
      including surgery, chemotherapy, radiotherapy, hormone therapy and targeted
      therapy. The role of the nurse in caring for patients with breast cancer is also
      discussed.

PMID- 18610934
TI  - Female urethral catheterisation.

PMID- 18610935
TI  - Unaccustomed as I am...

PMID- 18610936
TI  - Birth of a French love affair.

PMID- 18610937
TI  - Smile therapy.

PMID- 18610938
TI  - Hydrated electron extinction coefficient revisited.
AB  - The extinction coefficient of the hydrated electron (e(-))aq generated by pulse
      radiolysis is evaluated relative to the methyl viologen radical cation (*)MV(+),
      whose extinction coefficient at 605 nm has been carefully measured in the past.
      We find that the room temperature (e(-))aq extinction coefficients reported in
      the literature are underestimated by 10-20%. We obtain = 22,700 M(-1) cm(-1) for
      the 20 degrees C hydrated electron at 720 nm, assuming the (*)MV(+) extinction is
      13,700 M(-1) cm(-1) at 605 nm. This has implications both for second-order
      reaction rate measurements of (e(-))aq and for the estimate of its integrated
      oscillator strength.

PMID- 18610939
TI  - Resonant nonlinear absorption in Zn-phthalocyanines.
AB  - In this work, we investigate the nonlinear absorption dynamics of Zn
      phthalocyanine in dimethyl sulfoxide (DMSO). We used single pulse and pulse train
      Z-scan techniques to determine the dynamics and absorption cross-sections of
      singlet and triplet states at 532 nm. The excited singlet state absorption cross
      section was determined to be 3.2 times higher than the ground state one, giving
      rise to reverse saturable absorption. We also observed that reverse saturable
      absorption occurs from the triplet state, after its population by intersystem
      crossing, whose characteristic time was determined to be 8.9 ns. The triplet
      state absorption cross-section determined is 2.6 times higher than the ground
      state one. In addition, we used the white light continuum Z-scan to evaluate the
      singlet excited state spectrum from 450 to 710 nm. The results show two well
      defined regions, one above 600 nm, where reverse saturable absorption is
      predominant. Below 600 nm, we detected a strong saturable absorption. A three
      energy-level diagram was used to explain the experimental results, leading to the
      excited state absorption cross-section determination from 450 nm up to 710 nm.

PMID- 18610940
TI  - Accurate benchmark calculation of the reaction barrier height for hydrogen
      abstraction by the hydroperoxyl radical from methane. Implications for
      C(n)H(2n+2) where n = 2 --> 4.
AB  - The CH4 + HO2(*) reaction is studied by using explicitly correlated coupled
      cluster theory with singles and doubles (CCSD-R12) in a large 19s14p8d6f4g3h
      basis (9s6p4d3f for H) to approach the basis-set limit at the coupled-cluster
      singles-doubles level. A correction for connected triple excitations is obtained
      from the conventional CCSD(T) coupled-cluster approach in the correlation
      consistent quintuple-zeta basis (cc-pV5Z). The highly accurate results for the
      methane reaction are used to calibrate the calculations of the hydroperoxyl
      radical hydrogen abstraction from other alkanes. For the alkanes C(n)H(2n+2) with
      n = 2 --> 4, the reactions are investigated at the CCSD(T) level in the
      correlation-consistent triple-zeta (cc-pVTZ) basis. The results are adjusted to
      the benchmark methane reaction and compared with those from other approaches that
      are commonly used in the field such as CBS-QB3, CBS-APNO, and density functional
      theory. Rate constants are computed in the framework of transition state theory,
      and the results are compared with previous values available.

PMID- 18610941
TI  - The different aromatic characters of some localized benzene derivatives.
AB  - Localized benzene derivatives can be separated into two classes, one that retains
      large diamagnetic ring currents and a second that loses the diamagnetic ring
      current. Energetic criteria and NICS scan are used to evaluate the nature of the
      two classes. Huckel-type treatment, MO analysis, and comparison to model
      compounds suggest that there is no connection between geometric localization and
      the loss of aromaticity.

PMID- 18610942
TI  - Effects of complex formation on vibrational circular dichroism spectra.
AB  - The determination of absolute configurations of chiral compounds using VCD is
      performed by comparing measured vibrational circular dichroism (VCD) spectra with
      calculated spectra. The process is based on two facts: the two enantiomers have
      rotational strengths of opposite sign, and the absolute configuration of the
      molecule used in the calculation is known. However, calculations on isolated
      molecules very often predict VCD intensities of very different magnitude or even
      different signs compared to the spectra measured in solution. Therefore, we have
      carefully analyzed what type of changes are induced by complexation of a solvent
      molecule to a solute. In the theoretical example of benzoyl-benzoic acid (in a
      particular chiral conformation) hydrogen bonded to the achiral NH3, we
      distinguish six cases, ranging from no or very small changes in the rotational
      strengths of solute modes (case A) to changes of sign of rotational strengths
      (case B), changes in magnitude (case C), nonzero rotational strengths for modes
      of the achiral solvent ("transfer of chirality", case D), large frequency shifts
      accompanied by giant enhancements of the IR and VCD intensities of modes involved
      in hydrogen bonding (case E), and emergence of new peaks (case F). In this work,
      all of these situations will be discussed and their origin will be elucidated. On
      the basis of our analysis, we advocate that codes for VCD rotational strength
      calculation should output for each mode i the angle xi(i) between the electric
      and magnetic transition dipole moments because only "robust modes" with xi far
      from 90 degrees should be used for the determination of the absolute
      configuration.

PMID- 18610943
TI  - Determination of optimal rhodamine fluorophore for in vivo optical imaging.
AB  - Optical imaging has the potential to improve the efficacy of surgical and
      endoscopic approaches to cancer treatment; however, the optimal type of
      fluorescent probe has not yet been established. It is well-known that rhodamine
      core-derived fluorophores offer a combination of desirable properties such as
      good photostability, high extinction coefficient, and high fluorescence quantum
      yield. However, despite the ubiquitous use of rhodamine fluorophores for in vivo
      optical imaging, it remains to be determined if unique chemical properties among
      individual rhodamine core family members affect fluorophore parameters critical
      to in vivo optical imaging applications. These parameters include preserved
      fluorescence intensity in low pH environments, similar to that of the
      endolysosome; efficient fluorescence signal despite conformational changes to
      targeting proteins as may occur in harsh subcellular environments; persistence of
      fluorescence after cellular internalization; and sufficient signal-to-background
      ratios to permit the identification of fluorophore-targeted tumors. In the
      present study, we conjugated 4 common rhodamine-core based fluorescent dyes to a
      clinically feasible and quickly internalizing D-galactose receptor targeting
      reagent, galactosamine serum albumin (GmSA), and conducted a series of in vitro
      and in vivo experiments using a metastatic ovarian cancer mouse model to
      determine if differences in optical imaging properties exist among rhodamine
      fluorophores and if so, which rhodamine core possesses optimal characteristics
      for in vivo imaging applications. Herein, we demonstrate that the rhodamine
      fluorophore, TAMRA, is the most robust of the 4 common rhodamine fluorophores for
      in vivo optical imaging of ovarian cancer metastases to the peritoneum.

PMID- 18610945
TI  - Computational study of the oxidation and decomposition of dibenzofuran under
      atmospheric conditions.
AB  - The atmospheric degradation of dibenzofuran (DF) initiated by OH addition has
      been studied by using density functional theory (B3LYP method). Site C1 in DF is
      predicted to be the favored site for OH addition, with a branching ratio of 0.61
      to produce a DF-OH(1) adduct. The calculated reaction rate constant for OH
      addition to DF has been used to predict the atmospheric lifetime of DF to be 0.45
      day. Three different modes of attack of O2 ((3)Sigma(g)) on DF-OH(1) have been
      examined. Abstraction of hydrogen gem to OH in DF-OH(1) by O2 ((3)Sigma(g))
      (producing 1-dibenzofuranol I) and dioxygen addition in the three radical sites
      in cis and trans orientation (relative to the ispo-added OH) of the pi
      delocalized electron system of DF-OH(1) are feasible under atmospheric
      conditions. The free energy of activation (at 298.15 K) for the formation of 1
      dibenzofuranol is 15.1 kcal/mol with a free energy change of -36.3 kcal/mol,
      while the formation of DF-OH(1)-O2 adducts are endergonic by 9.2-21.8 kcal/mol
      with a 16.3-23.6 kcal/mol free energy of activation. On the basis of the
      calculated reaction rate constants, the formation of 1-dibenzofuranol is more
      important than the formation of DF-OH-O2 adducts. The results presented here are
      a first attempt to gain a better understanding of the atmospheric oxidation of
      dioxin-like compounds on a precise molecular basis.

PMID- 18610944
TI  - Systematic investigation of polyamidoamine dendrimers surface-modified with
      poly(ethylene glycol) for drug delivery applications: synthesis,
      characterization, and evaluation of cytotoxicity.
AB  - Surface modification of amine-terminated polyamidoamine (PAMAM) dendrimers by
      poly(ethylene glycol) (PEG) groups generally enhances water-solubility and
      biocompatibility for drug delivery applications. In order to provide guidelines
      for designing appropriate dendritic scaffolds, a series of G3 PAMAM-PEG dendrimer
      conjugates was synthesized by varying the number of PEG attachments and chain
      length (shorter PEG 550 and PEG 750 and longer PEG 2000). Each conjugate was
      purified by size exclusion chromatography (SEC) and the molecular weight (MW) was
      determined by (1)H NMR integration and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS). NOESY experiments
      performed in D 2O on selected structures suggested no penetration of PEG chains
      to the central PAMAM domain, regardless of chain length and degree of
      substitution. CHO cell cultures exposed to PAMAM-PEG derivatives (< or =1 microM)
      showed a relatively high cell viability. Generally, increasing the degree of PEG
      substitution reduced cytotoxicity. Moreover, compared to G3 PAMAM dendrimers that
      were N-acetylated to varying degrees, a lower degree of surface substitution with
      PEG was needed for a similar cell viability. Interestingly, when longer PEG 2000
      was fully incorporated on the surface, cell viability was reduced at higher
      concentrations (32 muM), suggesting increased toxicity potentially by forming
      intermolecular aggregates. A similar observation was made for anionic carboxylate
      G5.5 PAMAM dendrimer at the same dendrimer concentration. Our findings suggest
      that a lower degree of peripheral substitution with shorter PEG chains may
      suffice for these PAMAM-PEG conjugates to serve as efficient universal scaffolds
      for drug delivery, particularly valuable in relation to targeting or other ligand
      receptor interactions.

PMID- 18610946
TI  - Control of molecular structures and photophysical properties of zinc(II)
      porphyrin dendrimers using bidentate guests: utilization of flexible dendrimer
      structures as a controllable mold.
AB  - We have prepared supramolecular assemblies of hexaaryl-anchored polyester
      zinc(II) porphyrin dendrimers (6P(Zn)W, 12P(Zn)W, and 24P(Zn)W) with various
      bipyridyl guests (C(n)Py2; n = 1, 2, 4, 6, and 8) through self-assembled
      coordination to control the structures and photophysical properties. We
      comparatively investigated the photophysical properties of porphyrin dendrimers
      with and without guest binding by using ensemble and single-molecule
      spectroscopy. The spectrophotometric titration data of dendrimers with guest
      molecules provide a strong indication of the selective intercalation of bipyridyl
      guests into porphyrin dendrimers. The representative dendrimer assembly 12P(Zn)W
      [symbol: see text] C6Py2 exhibits increased fluorescence quantum yield and
      lifetime in ensemble measurements, as well as higher initial photon count rates
      with stepwise photobleaching behavior in the single-molecule fluorescence
      intensity trajectories (FITs) compared to 12P(Zn)W. At the single-molecule level,
      the higher photostability of 12P(Zn)W [symbol: see text] C6Py2 can be deduced
      from the long durations of the first emissive levels in the FITs. We attribute
      the change in photophysical properties of the dendrimer assemblies to their
      structural changes upon intercalation of guest molecules between porphyrin units.
      These results provide new insight into the control of porphyrin dendritic
      structures using appropriate bidentate guests in poor environmental conditions.

PMID- 18610947
TI  - Optimal charge and charge response determination through conformational space:
      global fitting scheme for representative charge and charge response kernel.
AB  - We propose a global fitting scheme derived in the least-squares sense to estimate
      the optimal partial charge and charge response kernel (CRK), partial
      differential(Q(a))/partial differential(V(b)), with the data collected from
      conformational space sampling. We applied the global fitting method to the 1
      butanol system and show the performance and accuracy of our global fitting
      procedure. In addition, we chose 1-pentanol as the test system for electronic
      structure change through conformational change and applied the global fitting
      method to it. From our study, it is indicated that intramolecular polarization
      can be influenced by intramolecular hydrogen bonding, and it is shown that our
      global fitting method can correspond to such a situation. Also, the global
      fitting procedure was tested on a large molecular system, 1-dodecanol. We show
      the results of the application of our fitting method for the system needed to
      sample large sets of data over a large conformational space. It is indicated that
      the nonlocality in intramolecular polarization in the alkyl chain sequence can be
      observed and that the large fluctuation of CRKs through nonbonded interactions
      such as intramolecular hydrogen bonding, as seen in the 1-pentanol case, can
      appear in common. The global fitting scheme we propose can be used for building
      molecular models considering polarization effects explicitly, even in the case of
      target systems that include many conformers.

PMID- 18610948
TI  - Cation spectroscopy and binding energy determination for 1,4-benzodioxan-Ar1 and 
      Ar2 complexes.
AB  - Cation vibronic spectra are measured for 1,4-benzodioxan (BZD) and van der Waals
      complexes of BZD with one and two Ar atoms using zero electron kinetic energy and
      mass analyzed threshold ionization spectroscopy. The spectra of the monomer
      cation were used to measure the frequencies of the two key low-frequency modes
      which had previously been extensively studied in the neutral S0 and S1 states.
      The aliphatic ring twisting mode, nu25, has an energy of 146 cm(-1) in the
      cation, intermediate between the values found in the S0 and S1 states. The
      bending, butterfly-like mode nu48 has an energy of 125 cm(-1), which is of higher
      frequency than either of the neutral states. The S1 spectra of the BZD-Ar1 and
      BZD-Ar2 complexes are recorded and observed to have modest red shifts from the
      monomer. The cation spectra of the complexes are also measured using mass
      analyzed threshold ionization spectroscopy including scans at higher energy which
      are used to determine the Ar binding energies. The energies for the loss of one
      Ar atom were determined to be 630 +/- 10 and 650 +/- 10 cm(-1) for BZD-Ar and BZD
      Ar2, respectively. The similar cation spectra and similar binding energies
      indicate that each Ar atom in BZD-Ar2 has a similar binding geometry. Quantum
      chemical calculations were performed which had fair agreement with the measured
      binding energies and give some insight into the specific binding geometry.

PMID- 18610949
TI  - Spin-forbidden transitions in the vicinity of the 2 (1)pi(u) <-- X (1)sigma(g)+
      band system of Rb2.
AB  - We have investigated the Rb2 475 nm system by resonance enhanced two-photon
      ionization spectroscopy in a pulsed molecular beam. Strong extra bands
      accompanying the 2 (1)Pi(u) v' = 5 - 8 <-- X (1)Sigma(g)(+) v'' = 0 bands were
      newly observed. Rotational analysis of the main and extra bands reveals that the
      2 (1)Pi(u) v' = 5 - 8 levels are significantly perturbed, mainly by the 3
      (3)Sigma(u)(+)(1 u) state and also by the 2 (3)Pi(u)(1 u) state. For the major
      perturber, 3 (3)Sigma(u)(+)(1 u), the intensity borrowing has been found to be
      facilitated by the 2 (1)Pi(u)-3 (3)Sigma(u)(+)(1 u) potential energy curve
      crossing near 21,100 cm(-1). For the vibronic-band intensities of the 2
      (3)Pi(u)(1 u) v' <-- X (1)Sigma(g)(+) v'' = 0 transitions observed in this
      spectral region, intensity borrowing was most effective when the 2 (3)Pi(u)(1 u)
      levels were close to the 3 (3)Sigma(u)(+)(1 u) levels. A deperturbation fit for
      the perturbing bands has provided the 2 (1)Pi(u)-3 (3)Sigma(u)(+)(1 u) coupling
      constants.

PMID- 18610950
TI  - Dissociative ionization of Na2 via repulsive Rydberg states: elucidating
      femtosecond dynamics with nanosecond lasers.
AB  - We have studied the dissociative ionization behavior of Na2 molecules using two
      color, three photon optical-optical double resonance enhanced excitation via the
      A(1)Sigma(u)(+) and the 2(1)Pi(g) states. Excess energy ranges from about 150 to
      about 1500 cm(-1) above threshold for dissociative ionization into ground-state
      Na and Na(+). Slow atomic Na(+) fragments and Na2(+) molecular ions are detected
      using a linear time-of-flight spectrometer operated in low field extraction, core
      sampling mode. To explain the observed energy dependence of the Na(+)/Na2(+)
      branching ratio, we introduce a semiclassical model for the underlying decay
      dynamics. Franck-Condon overlap densities for bound-free transitions starting in
      2(1)Pi(g) vibrational levels indicate that atomic Na(+) fragments are primarily
      produced via Rydberg states, with principal quantum number n between 5 and 12,
      converging to the repulsive 1(2)Sigma(u)(+) first excited-state potential of
      Na2(+). Dynamics along these Rydberg curves involves competition between
      electronic (autoionizing) and nuclear (dissociative) degrees of freedom. Within
      the model, the autoionization lifetime tau auto is the only one free parameter
      available to fit calculated Na(+)/Na2(+) branching ratios as a function of excess
      energy to the observed values. The lifetime is assumed to be the same multiple c
      of the Bohr period of each Rydberg potential. A chi(2)-minimization procedure
      yields, for the range of principal quantum numbers involved, a most likely value
      of c = 1.5 +/- 0.3, implying that on average the Rydberg electron completes only
      1 to 2 orbits before interaction with the excited core electron leads to
      autoionization.

PMID- 18610951
TI  - Water dissociation on alpha1-hafnium and ytterbium substituted Dawson
      polyoxotungstates: a density functional theory study.
AB  - Density functional theory (DFT) calculations were devised to get insight into
      Lewis acidic catalysis by POMs, especially on the intriguing activation of
      complexed water molecules that was observed in some experimental cases.
      Computationally, it appears that deprotonation is feasible with [alpha(1)
      Hf(H(2)O)P(2)W(17)O(61)](6-), but not with [alpha(1)-Yb(H(2)O)P(2)W(17)O(61)](7
      ). This reflects the difference of the electronic structures (diamagnetic for
      hafnium POM, paramagnetic for ytterbium POM). From a mechanistical point of view,
      indirect Bronsted catalysis cannot be excluded in the hafnium case, especially
      for Mannich reactions. But our calculations show that catalysis by [alpha(1)
      Yb(H(2)O)P(2)W(17)O(61)](7-) (and presumably all the lanthanide series) proceeds
      through direct complexation of the substrates to the POM.

PMID- 18610952
TI  - Analysis of low-frequency phonons in guanosine dihydrate based on molecular
      dynamics simulations.
AB  - Fourier analysis, using the atomic trajectory calculated by molecular dynamics
      simulation at 300 K, is applied to the study of low-frequency phonons of guanine
      dihydrate. The vibrational modes of guanine bases are analyzed, and the optically
      active modes associated with the guanine moieties are extracted. There are a few
      significant peaks in the low-frequency region. A possible assignment of the Raman
      active mode near 27 cm(-1), whose origin would be common to the S-mode of DNA
      double helices, is discussed.

PMID- 18610953
TI  - A technique for in situ monitoring of crystallization from solution by solid
      state 13C CPMAS NMR spectroscopy.
AB  - We report a technique for carrying out in situ solid-state NMR studies of
      crystallization from solution, allowing the evolution of different solid state
      structures (polymorphs) produced during the crystallization process to be
      identified. The technique exploits selectivity in NMR properties (specifically,
      the efficiency of cross-polarization from (1)H to (13)C) between molecules in the
      solid and solution states, such that the first solid particles produced during
      the crystallization process are observed selectively, without detecting any
      signal from dissolved solute (or solvent) molecules. The application of the
      technique is demonstrated to reveal new insights concerning an isotope effect on
      the polymorphic outcome of crystallization of glycine from water. As revealed by
      this example, the in situ solid-state NMR approach reported here creates
      significant new opportunities for probing and understanding details of the
      evolution of solid state structures produced during crystallization from
      solution.

PMID- 18610954
TI  - Elastic incoherent neutron scattering on systems of biophysical interest: mean
      square displacement evaluation from self-distribution function.
AB  - In the present work an operational recipe for the mean square displacement (MSD)
      determination, highlighting the connection between the self-distribution function
      and average statistical values, is presented. The determination of the MSD and of
      its contributions associated with different mechanisms, together with their
      thermal behavior, is performed by evaluating the self-distribution function
      derived by elastic incoherent neutron scattering (EINS). The approach is tested
      on EINS data collected by the backscattering spectrometer IN13 (ILL, Grenoble,
      France) on two model systems such as dry myoglobin in trehalose and poly(ethylene
      glycol) with mean molecular weight M(w) = 400 (PEG 400).

PMID- 18610955
TI  - Theory and computer simulation of solute effects on the surface tension of
      liquids.
AB  - A complete description of the thermodynamics of planar mixed solute-solvent
      interfaces suitable for the analysis of computer simulation data is provided. The
      approach uses surface probability distributions to characterize the interface
      regions, coupled with radial distribution functions and the Kirkwood-Buff theory
      of solutions to characterize the bulk solution properties. The approach is then
      used to understand the relationship between changes in the surface tension, the
      degree of surface adsorption or depletion, and the bulk solution properties of
      two aqueous solute systems. The first, aqueous NaCl solutions, provides an
      example of a surface excluded solute. The second, aqueous methanol solutions,
      provides an example of a surface adsorbed solute. The numerical results support
      the theoretical relationships described here and provide a consistent picture of
      the thermodynamics of solution interfaces involving any number of components
      which can be applied to a wide variety of systems.

PMID- 18610956
TI  - Cross-diffusion in a water-in-oil microemulsion loaded with malonic acid or
      ferroin. Taylor dispersion method for four-component systems.
AB  - We describe an improved Taylor dispersion method for four-component systems,
      which we apply to measure the main- and cross-diffusion coefficients in an
      Aerosol OT water-in-oil microemulsion loaded with one of the reactants of the
      Belousov-Zhabotinsky (BZ) reaction, water(1)/AOT(2)/R(3)/octane(4) system, where
      R is malonic acid or ferroin. With [H(2)O]/[AOT] = 11.8 and volume droplet
      fraction phi d = 0.18, when the microemulsion is below the percolation
      transition, the cross-diffusion coefficients D(13) and D(23) are large and
      positive ( D(13)/ D(33) congruent with 14, D(23)/ D(33) congruent with 3) for
      malonic acid and large and negative for ferroin ( D(13)/ D(33) congruent with 
      112, D(23)/ D(33) congruent with -30) while coefficients D(31) and D(32) are
      small and negative for malonic acid ( D(31)/ D(33) congruent with -0.01, D(32)/
      D(33) congruent with -0.14) and small and positive for ferroin ( D(31)/ D(33)
      congruent with 5 x 10(-4), D(32)/ D(33) congruent with 8 x 10(-3)). These data
      represent the first direct determination of cross-diffusion effects in a pattern
      forming system and of the full matrix of diffusion coefficients for a four
      component system. The results should provide a basis for modeling pattern
      formation in the BZ-AOT system.

PMID- 18610957
TI  - Hydrogen bond breaking mechanism and water reorientational dynamics in the
      hydration layer of lysozyme.
AB  - The mechanism and the rate of hydrogen bond-breaking in the hydration layer
      surrounding an aqueous protein are important ingredients required to understand
      the various aspects of protein dynamics, its function, and stability. Here, we
      use computer simulation and a time correlation function technique to understand
      these aspects in the hydration layer of lysozyme. Water molecules in the layer
      are found to exhibit three distinct bond-breaking mechanisms. A large angle
      orientational jump of the donor water molecule is common among all of them. In
      the most common ( approximately 80%) bond-breaking event in the layer, the new
      acceptor water molecule comes from the first coordination shell (initially within
      3.5 A of the donor), and the old acceptor water molecule remains within the first
      coordination shell, even after the bond-breaking. This is in contrast to that in
      bulk water, in which both of the acceptor molecules involve the second
      coordination shell. Additionally, the motion of the incoming and the outgoing
      acceptor molecules involved is not diffusive in the hydration layer, in contrast
      to their observed diffusive motion in the bulk. The difference in rotational
      dynamics between the bulk and the hydration layer water molecules is clearly
      manifested in the calculated time-dependent angular van Hove self-correlation
      function ( G(theta, t)) which has a pronounced two-peak structure in the layer,
      and this can be traced to the constrained translational motion in the layer. The
      longevity of the surrounding hydrogen bond network is found to be significantly
      enhanced near a hydrophilic residue.

PMID- 18610958
TI  - Amphiphilic siloxane phosphonate macromolecule monolayers at the air/water
      interface: effects of structure and temperature.
AB  - A comprehensive study is reported of Langmuir-Blodgett (LB) films (spread at the
      air/water interface using the Langmuir balance technique) composed of surface
      active, nonionic, and OH-free amphiphilic siloxane phosphonate ester
      macromolecules. Analysis is made on three molecular structures in the form of
      linear polymer poly(diethylphosphono-benzyl-alphabeta-ethyl methylsiloxane)
      (PPEMS), cyclic oligomer methylphosphonobenzyl-alphabeta-ethyl cyclosiloxane
      (MPECS), and copolymer poly(PEMS-co-DMS). The surface pressure-surface area (pi 
      A) isotherms of homopolymer at 3-40 degrees C show a clear temperature-induced
      phase transition (plateaus at pit approximately 17-19 mN/m) below 10 degrees C.
      The magnitude of the transition substantially increases upon lowering the
      temperature (partial differential DeltaAt/ partial differential T approximately 
      0.1 nm2 unit(-1) deg(-1) and partial differential pi t / partial differential T
      approximately -0.25 mN m(-1) deg(-1)). The positive entropy and enthalpy gain
      infers that strong coupling with the subphase and excess hydration attributed to
      hydrogen bonding between the P=O bond and the subphase prevails at low
      temperatures. The cyclic oligomer MPECS forms a condensed monolayer at the
      air/water interface that does not display a similar transition in the
      experimental temperature range. The temperature sensitivity of MPECS film is
      observed only in the collapsed region. The nature of the interaction with the
      subphase is similar for MPECS and PPEMS, indicating that the size and thermal
      mobility are the controlling factors in these processes. The elasticity plot
      reveals two distinct states (above and below transition). This observation is
      supported by BAM images that show irregular spiral structures below 10 degrees C.
      The transition occurring in the copolymer at 20 degrees C is due to relaxation of
      the PDMS component. The two maxima shown in the elasticity plot indicate additive
      fractions of PPEMS and PDMS. The surface areas of these macromolecules in the
      relaxed (1.48 nm2/unit) and packed (0.45 nm2/unit) forms obtained by PM3 modeling
      agree well with the experimental data and seem to indicate that the siloxane
      chain is being lifted off the subphase by the hydrophobic phenylic part of the
      molecule.

PMID- 18610959
TI  - Binding interaction of cationic phenazinium dyes with calf thymus DNA: a
      comparative study.
AB  - Absorption, steady-state fluorescence, steady-state fluorescence anisotropy, and
      intrinsic and induced circular dichroism (CD) have been exploited to explore the
      binding of calf thymus DNA (ctDNA) with three cationic phenazinium dyes, viz.,
      phenosafranin (PSF), safranin-T (ST), and safranin-O (SO). The absorption and
      fluorescence spectra of all the three dyes reflect significant modifications upon
      interaction with the DNA. A comparative study of the dyes with respect to
      modification of fluorescence and fluorescence anisotropy upon binding, effect of
      urea, iodide-induced fluorescence quenching, and CD measurements reveal that the
      dyes bind to the ctDNA principally in an intercalative fashion. The effect of
      ionic strength indicates that electrostatic attraction between the cationic dyes
      and ctDNA is also an important component of the dye-DNA interaction. Intrinsic
      and induced CD studies help to assess the structural effects of dyes binding to
      DNA and confirm the intercalative mode of binding as suggested by fluorescence
      and other studies. Finally it is proposed that dyes with bulkier substitutions
      are intercalated into the DNA to a lesser extent.

PMID- 18610960
TI  - Folding kinetics of a naturally occurring helical peptide: implication of the
      folding speed limit of helical proteins.
AB  - The folding mechanism and dynamics of a helical protein may strongly depend on
      how quickly its constituent alpha-helices can fold independently. Thus, our
      understanding of the protein folding problem may be greatly enhanced by a
      systematic survey of the folding rates of individual alpha-helical segments
      derived from their parent proteins. As a first step, we have studied the
      relaxation kinetics of the central helix (L9:41-74) of the ribosomal protein L9
      from the bacterium Bacillus stearothermophilus , in response to a temperature
      jump ( T-jump) using infrared spectroscopy. L9:41-74 has been shown to exhibit
      unusually high helicity in aqueous solution due to a series of side chain-side
      chain interactions, most of which are electrostatic in nature, while still
      remaining monomeric over a wide concentration range. Thus, this peptide
      represents an excellent model system not only for examining how the folding rate
      of naturally occurring helices differs from that of the widely studied alanine
      based peptides, but also for estimating the folding speed limit of (small)
      helical proteins. Our results show that the T-jump induced relaxation rate of
      L9:41-74 is significantly slower than that of alanine-based peptides. For
      example, at 11 degrees C its relaxation time constant is about 2 micros, roughly
      seven times slower than that of SPE(5), an alanine-rich peptide of similar chain
      length. In addition, our results show that the folding rate of a truncated
      version of L9:41-74 is even slower. Taken together, these results suggest that
      individual alpha-helical segments in proteins may fold on a time scale that is
      significantly slower than the folding time of alanine-based peptides.
      Furthermore, we argue that the relaxation rate of L9:41-74 measured between 8 and
      45 degrees C provides a realistic estimate of the ultimate folding rate of
      (small) helical proteins over this temperature range.

PMID- 18610961
TI  - Aromatic amino acids providing characteristic motifs in the Raman and SERS
      spectroscopy of peptides.
AB  - Raman and surface-enhanced Raman spectroscopies (SERS) are potentially important
      tools in the characterization of biomolecules such as proteins and DNA. In this
      work, SERS spectra of three cysteine-containing aromatic peptides: tryptophan
      cysteine, tyrosine-cysteine, and phenylalanine-cysteine, bound to Au nanoshell
      substrates, were obtained, and compared to their respective normal Raman spectra.
      While the linewidths of the SERS peaks are significantly broadened (up to 70%),
      no significant spectral shifts (<6 cm (-1)) of the major Stokes modes were
      observed between the two modalities. We show that the Raman and SERS spectra of
      penetratin, a cell-penetrating peptide oligomer, can be comprised quite reliably
      from the spectra of its constituent aromatic amino acids except in the backbone
      regions where the spectral intensities are critically dependent on the length and
      conformations of the probed molecules. From this study we conclude that, together
      with protein backbone groups, aromatic amino acid residues provide the
      overwhelmingly dominant features in the Raman and SERS spectra of peptides and
      proteins when present. It follows that the Raman modes of these three small
      constructed peptides may likely apply to the assignment of Raman and SERS
      features in the spectra of other peptides and proteins.

PMID- 18610962
TI  - Effect of side-chain length on the side-chain dynamics of alpha-helical poly(L
      glutamic acid) as probed by a fluorescence blob model.
AB  - Two series of pyrene-labeled poly(glutamic acid) (Py-PGA) were synthesized
      utilizing two different linkers for pyrene attachment, namely 1-pyrenemethylamine
      (PMA) and 1-pyrenebutylamine (PBA). Several Py-PGAs were synthesized for each
      series with pyrene contents ranging from 4 to 15 mol %. Py-PGA forms a rigid
      alpha-helix in DMF that effectively locks the backbone in place, thus enabling
      only side-chain or linker motions to be monitored by time-resolved fluorescence.
      Time-resolved fluorescence decays were acquired for the pyrene monomer of the Py
      PGA constructs and the fluorescence blob model (FBM) was used to quantify the
      dynamics of the different linkers connecting pyrene to the backbone. Nitromethane
      was used to shorten the lifetime of the pyrene monomer, in effect controlling the
      probing time of the pyrene group, from 50 to 155 ns for PGA-PBA and from 50 to
      215 ns for PGA-PMA. The FBM analysis of the fluorescence decays led to the
      conclusion that excimer formation around the rigid alpha-helix backbone takes
      place in a compact environment. The number of glutamic acid units within a blob,
      N blob, decreased only slightly with decreasing probing time for both Py-PGA
      constructs as a result of the compact distribution of the chromophores around the
      alpha-helix. The PGA alpha-helix was modeled using Hyperchem software and the
      ability of two pyrene groups to encounter was evaluated as they were separated by
      increasing numbers of amino acids along the alpha-helix. The number of amino
      acids required for two pyrenes to lose their ability to overlap and form excimer
      matched closely the N blob values retrieved using the FBM.

PMID- 18610964
TI  - Nanocomposite ion gels based on silica nanoparticles and an ionic liquid: ionic
      transport, viscoelastic properties, and microstructure.
AB  - The dispersion of silica nanoparticles made an ionic liquid, 1-ethyl-3-methyl
      imidazolium bis(trifluoromethanesulfonyl)amide ([C(2)mim][NTf(2)]), gelled even
      by the addition of 2-3 wt %, due to the formation of interconnected particulate
      silica networks in [C(2)mim][NTf(2)]. The ionic transport and viscoelastic
      properties of these nanocomposite ion gels were investigated in relation to the
      microstructure. Despite their solid-like behavior, the nanocomposite ion gels
      exhibited a high ionic conductivity of approximately 10(-2) S cm(-1) at 30
      degrees C, which is comparable to that of neat [C(2)mim][NTf(2)]. Intriguing
      viscoelastic responses, such as shear-thinning and shear-induced sol-gel
      transitions, were found in all of the nanocomposite ion gels. By adjusting the
      silica concentration, the elastic modulus ( G') could be precisely controlled in
      a range of more than 3 orders of magnitude and reached approximately 10(6) Pa
      without a considerable decrease in the ionic conductivity; the characteristic
      viscoelastic response was also maintained. For the aggregation mechanism in [C 2
      mim][NTf(2)], the reaction-limited cluster aggregation (RLCA) model was proposed
      by rheology and light scattering measurements.

PMID- 18610963
TI  - Molecular fibers based on the honeycomb-like self-assembly of an alpha-helical
      polypeptide.
AB  - We have succeeded in fabricating well-grown molecular fibers of a polypeptide on
      substrates by using a conventional solution spin-coating and drying process.
      These molecular fibers were found to consist of a honeycomb-like molecular
      assembly formed via the hexagonal close packing of the polypeptide chains in the
      alpha-helix conformation.

PMID- 18610965
TI  - Temperature behavior of the electric field-induced entropy increment within a
      homologous series of nematogenic compounds.
AB  - Based on the temperature behavior of the entropy increment induced by the probing
      electric field in the isotropic phase of mesogenic compounds belonging to the
      homologous series C(n)H(2n+1)PhCOOPhCN ( n = 4-10), it is found that an ability
      to the dipolar aggregation of the molecules depends on the alkyl tail length,
      and, in particular, the ability is strongly reinforced when the number n changes
      from 7 to 8. The role of the molecular structure in the self-assembling process
      is discussed.

PMID- 18610966
TI  - Guanidinium chloride molecular diffusion in aqueous and mixed water-ethanol
      solutions.
AB  - Solutions containing guanidinium chloride (GdmCl), or equivalently guanidine
      hydrochloride (GdnHCl), are commonly used to denature macromolecules such as
      proteins and DNA in, for example, microfluidics studies of protein unfolding. To
      design and study such applications, it is necessary to know the diffusion
      coefficients for GdmCl in the solution. To this end, we use molecular dynamics
      simulations to calculate the diffusion coefficients of GdmCl in water and in
      water-ethanol solutions, for which no direct experimental measurements exist. The
      fully atomistic simulations show that the guandinium cation Gdm (+) diffusion
      decreases as the concentration of both Gdm (+) and ethanol in the solution
      increases. The simulations are validated against available literature data, both
      transformed measured viscosity values and computed diffusion coefficients, and we
      show that a prudent choice of water model, namely TIP4P-Ew, gives calculated
      diffusion coefficients in good agreement with the transformed measured viscosity
      values. The calculated Gdm (+) diffusion behavior is explained as a dynamic
      mixture of free cation, stacked cation, and ion-paired species in solution, with
      weighted contributions to Gdm (+) diffusion from the stacked and paired states
      helping explain measured viscosity data in terms of atom-scale dynamics.

PMID- 18610967
TI  - Role of chirality of the sugar ring in the ribosomal peptide synthesis.
AB  - We present a theoretical analysis of the role of the natural chirality of the
      sugar ring ( D-enantiomeric form) in the peptide synthesis reaction in ribosome.
      The study is based on a model from the crystal structure of the ribosomal subunit
      of Haloarcula marismortui using hybrid quantum mechanical-molecular mechanical
      method. The result indicates that the natural heterochiral sugar-amino acid
      combination ( D: L) is most favorable for the formation of the peptide bond
      within the structure of peptidyl transferase center (PTC). Other possible
      combinations of unnatural chiral form of the sugar-amino acid pair are
      unfavorable to perform the reaction within the PTC. The presence of the sugar
      ring has favorable influence on the rotatory path. The chirality of the 2' carbon
      of the sugar ring is vital for the peptide synthesis. Alteration of the
      stereochemistry or removal of chirality at the 2' center makes the rate as
      several orders slower in magnitude. This is in agreement with the recent
      experimental result that the replacement of the 2' OH by H or F reduces the rate
      by several orders of magnitude. Two different mechanisms for the catalytic effect
      of the stereochemistry of 2' OH are investigated. In one mechanism, the 2' OH is
      involved in proton shuttle, and in the second mechanism, the OH group acts as an
      anchoring group. The transition state barriers of both mechanisms are found to be
      comparable. The natural chirality of the 2' center helps lowering the transition
      state barrier height of the reaction substantially compared with the cases where
      the 2' center is made achiral or with altered chirality. Thus, the
      stereochemistry of the 2' center has a major role in synthesis. Few surrounding
      residues like U2620, A2486, G2618, and C2487 have favorable influence on rotatory
      path, while the residues like U2541, C2104, C2105, A2485, C2542, C2608, U2619,
      and A2637 have little influence. The present study shows that the natural
      chirality of the sugar ring and amino acid makes a perfect heteropair within the
      PTC to carry out peptide synthesis with high efficiency.

PMID- 18610968
TI  - A nanoreactor for tuning the chemical reactivity of a solute.
AB  - Present results demonstrate that the redox potential and hence the chemical
      reactivity of a solute dissolved in a polymer-surfactant supramolecular assembly,
      considered as a nanoreactor, can be tuned substantially by changing the
      composition of the supramolecular assembly. It is understood from detailed study
      that, on changing the polymer-surfactant composition of the supramolecular
      assembly, the probe undergoes a change in its location in these nanoreactors and
      accordingly its physical and chemical properties can be modulated.

PMID- 18610969
TI  - Precursors to [FeFe]-hydrogenase models: syntheses of Fe2(SR)2(CO)6 from CO-free
      iron sources.
AB  - This report describes routes to iron dithiolato carbonyls that do not require
      preformed iron carbonyls. The reaction of FeCl 2, Zn, and Q 2S 2C n H 2 n (Q (+)
      = Na (+), Et 3NH (+)) under an atmosphere of CO affords Fe 2(S 2C n H 2 n )(CO) 6
      ( n = 2, 3) in yields >70%. The method was employed to prepare Fe 2(S 2C 2H 4)(
      (13)CO) 6. Treatment of these carbonylated mixtures with tertiary phosphines,
      instead of Zn, gave the ferrous species Fe 3(S 2C 3H 6) 3(CO) 4(PR 3) 2, for R =
      Et, Bu, and Ph. Like the related complex Fe 3(SPh) 6(CO) 6, these compounds
      consist of a linear arrangement of three conjoined face-shared octahedral
      centers. Omitting the phosphine but with an excess of dithiolate, we obtained the
      related mixed-valence triiron species [Fe 3(S 2C n H 2 n ) 4(CO) 4] (-). The
      highly reducing all-ferrous species [Fe 3(S 2C n H 2 n ) 4(CO) 4] (2-) is
      implicated as an intermediate in this transformation. Reactive forms of iron,
      prepared by the method of Rieke, also combined with dithiols under a CO
      atmosphere to give Fe 2(S 2C n H 2 n )(CO) 6 in modest yields under mild
      conditions. Studies on the order of addition indicate that ferrous thiolates are
      formed prior to the onset of carbonylation. Crystallographic characterization
      demonstrated that the complexes Fe 3(S 2C 3H 6) 3(CO) 4(PEt 3) 2 and PBnPh 3[Fe
      3(S 2C 3H 6) 4(CO) 4] feature high-spin ferrous and low-spin ferric as the
      central metal, respectively.

PMID- 18610970
TI  - CO-migration in the ligand substitution process of the chelating diphosphite
      diiron complex (mu-pdt)[Fe(CO)3][Fe(CO){(EtO)2PN(Me)P(OEt)2}].
AB  - Selective synthetic routes to isomeric diiron dithiolate complexes containing the
      (EtO) 2PN(Me)P(OEt) 2 (PNP) ligand in an unsymmetrical chelating role, for
      example, (mu-pdt)[Fe(CO) 3][Fe(CO)(kappa (2)-PNP)] ( 3) and as a symmetrically
      bridging ligand in (mu-pdt)(mu-PNP)[Fe(CO) 2] 2 ( 4), have been developed. 3 was
      converted to 4 in 75% yield after extensive reflux in toluene. The reactions of 3
      with PMe 3 and P(OEt) 3 afforded bis-monodentate P-donor complexes (mu
      pdt)[Fe(CO) 2PR 3][Fe(CO) 2(PNP)] (PR 3 = PMe 3, 5; P(OEt) 3, 7), respectively,
      which are formed via an associative PMe 3 coordination reaction followed by an
      intramolecular CO-migration process from the Fe(CO) 3 to the Fe(CO)(PNP) unit
      with concomitant opening of the Fe-PNP chelate ring. The PNP-monodentate
      complexes 5 and 7 were converted to a trisubstituted diiron complex (mu-pdt)(mu
      PNP)[Fe(CO)PR 3][Fe(CO) 2] (PR 3 = PMe 3, 6; P(OEt) 3, 8) on release of 1 equiv
      CO when refluxing in toluene. Variable-temperature (31)P NMR spectra show that
      trisubstituted diiron complexes each exist as two configuration isomers in
      solution. All diiron dithiolate complexes obtained were characterized by MS, IR,
      NMR spectroscopy, elemental analysis, and X-ray diffraction studies.

PMID- 18610972
TI  - Homoleptic selenium cyanides: attempted preparation of Se(CN)4 and
      redetermination of the crystal structure of Se(CN)2.
AB  - The preparation of Se(CN) 4 was attempted by the reaction of SeF 4 with Me 3SiCN
      at low temperatures. However, selenium tetracyanide could not be detected by NMR
      spectroscopy; instead, the decomposition product Se(CN) 2 was isolated and its
      crystal structure was redetermined. In the structure of Se(CN) 2, layers are
      present with secondary Se...N interactions. The structure of Se(CN) 4 and its
      reductive decomposition reaction has been calculated at the MP2 level of theory.

PMID- 18610971
TI  - Bulky N-substituted 1,3-benzazaphospholes: access via Pd-catalyzed C-N and C-P
      cross coupling, lithiation, and conversion to novel P=C-PtBu2 hybrid ligands.
AB  - The syntheses of novel bulky N-substituted 1,3-benzazaphospholes are presented,
      together with their reactions with tert-butyllithium and coupling with tBu 2PCl
      to novel P, P'-hybrid ligands that combine the highly basic and bulky di- tert
      butylphosphanyl group with pi-acidic low-coordinated phosphorus. The syntheses
      start with the preparation of new N-secondary 2-bromoanilines 1 by reduction of N
      acyl 2-bromoanilides or more generally by Pd-catalyzed selective monoamination of
      o-dibromobenzene, followed by Pd-catalyzed C-P coupling with P(OEt) 3 to the
      respective 2-anilino-phosphonates 2. The next steps are reduction to 2
      phosphanylanilines 3 and condensation with Me 2NCH(OMe) 2, which leads via
      phosphaalkenes 4 to the corresponding N-substituted benzazaphospholes 5. The
      reaction with tBuLi depends on the steric demand of the N substituent. Methyl,
      neopentyl-, and mesityl-derivatives were converted to P=C Li species 6 and
      coupled with tBu 2PCl to novel P=C-P tBu 2 ligands 7, whereas N-adamantyl and N
      2,6-diisopropylphenyl-derivatives prefer addition of tBuLi at the PC bond to form
      dihydroderivatives. The chemical shifts of the low-coordinated phosphorus of 5
      and 7 were found to reflect electronic and steric effects of the N substituents.
      The comparison of the crystal structures of N-neopentyl-1,3-benzazaphospholes 5
      and 7 gives evidence of steric repulsion between the adjacent di- tert-butyl and
      neopentyl groups by the preferred anti orientation of the P- tert-butyl groups
      and moderate deviations of C2 and P3 of 7b from the ring plane.

PMID- 18610974
TI  - Manipulating photochemical reactivity of coumarins within cucurbituril
      nanocavities.
AB  - Coumarin derivatives that are either cationic (7-ammonium) or neutral (7-hydroxy,
      7-methoxy, 6-methyl) form a 1:2 host-guest complex with cucurbit[8]uril (CB[8]).
      Direct irradiation of these coumarin@CB[8] complexes in water gives head-to-tail
      (HT) adduct as the major product. The nature of the functional group (polar or
      nonpolar) at the 6 or 7 position on the coumarin dictates the type of HT adduct (
      syn- or anti-). It is postulated that the available free volume and the
      hydrophobic confined environment are responsible for the observed selectivity.

PMID- 18610973
TI  - Direct catalytic asymmetric Mannich-type reaction of beta-keto phosphonate using
      a dinuclear Ni2-Schiff base complex.
AB  - Direct catalytic asymmetric Mannich-type reactions of beta-keto phosphonates are
      described. A homodinuclear Ni 2-Schiff base complex promoted the reaction at 0
      degrees C, giving beta-amino phosphonates in up to 90% yield, 20:1 dr, and 99%
      ee. Control experiments suggested that two Ni metals are important for achieving
      high yield and stereoselectivity.

PMID- 18610975
TI  - A reverse donor-acceptor bistable [2]catenane.
AB  - A [2]catenane, composed of a pi-electron-rich bis-1,5-dioxynaphthalene[38]crown10
      (BDNP38C10) ring, mechanically interlocked with a large macrocycle containing two
      disubstituted tetraarylmethane "speed bumps" and two different pi-electron
      deficient units--namely, naphthalene dimide (NpI) and bipyridinium (BIPY(2+))
      units--has been synthesized from a [2]rotaxane, containing the former recognition
      unit, after performing two sequential Cu(I)-catalyzed azide-alkyne cycloadditions
      with a linker containing the latter recognition unit. The product, which exists
      as a single co-conformer, wherein the BDNP38C10 ring encircles the NpI unit,
      undergoes equilibration to give approximately equal amounts of the other co
      conformer in which the BDNP38C10 ring encircles the BIPY(2+) unit.

PMID- 18610976
TI  - Catalyzed cyclizations leading to enrichment of functionality and chirality. A
      general approach to dibenzocyclooctadiene lignans from alpha,omega-diynes.
AB  - The [B-Sn]-mediated cyclization of alpha,omega-diynes results in not only an
      increase in the functionalizable groups (incorporated as highly versatile vinyl-B
      and vinyl-Sn groups) but also an increase in new serviceable stereochemical
      elements. The alkylidene functionalities at C7 and C8 offer unprecedented
      opportunities for the synthesis of highly functionalized dibenzocyclooctadienes.
      Examples of interiotherins and gomisins are provided.

PMID- 18610977
TI  - Highly fluorinated benzobisbenzothiophenes.
AB  - Expedient, facile syntheses of highly fluorinated benzobisbenzothiophenes (BBBT)
      are reported. Defined peripheral arrangements of sulfur and fluorine atoms lead
      to extensive crystalline networks of edge-to-edge S-F close contacts. The effects
      of various substitution patterns on self-assembly and electronic properties are
      described.

PMID- 18610978
TI  - Iminium salts of omega-dithiafulvenylpolyenals: an easy entry to the
      corresponding aldehydes and doubly proaromatic nonlinear optic-phores.
AB  - A short, high-yielding route to omega-dithiafulvenylpolyenals (1) via the
      corresponding iminium salts (2) and starting from trimethyl-1,3-dithiolium
      tetrafluoroborate is reported. The Knoevenagel reactions of either 1 or 2 with
      isoxazolone-containing acceptors afford merocyanines 7 and 9, in a process that
      is often accompanied by a vinylene-shortening side reaction. Experimental and
      theoretical studies reveal that compounds 7 and 9, featuring two proaromatic end
      groups, are strongly polarized and show good second-order nonlinear optical
      responses.

PMID- 18610979
TI  - Synthesis of substituted N-benzyl pyridones via an O- to N-alkyl migration.
AB  - A new LiI-promoted O- to N-alkyl migration has been developed for the conversion
      of O-alkylated 2-hydroxy pyridines, quinolines, and pyrimidines to the
      corresponding N-alkylated heterocycles in good to excellent yields (57-99%). This
      method serves as an efficient means for the preparation of N-benzyl pyridones,
      quinolones, and pyrimidones.

PMID- 18610980
TI  - Copper-mediated N-cyclopropylation of azoles, amides, and sulfonamides by
      cyclopropylboronic acid.
AB  - Reaction of azoles, amides, and sulfonamides in dichloroethane with readily
      available cyclopropylboronic acid in the presence of copper acetate and sodium
      carbonate afforded the N-cyclopropyl derivatives in good to excellent yields.

PMID- 18610981
TI  - Rearrangement of N,N-di-tert-butoxycarbonylpyridin-4-amines and formation of
      polyfunctional pyridines.
AB  - N, N-Di-tert-butoxycarbonylpyridin-4-amines were found to be rearranged to tert
      butyl 4-(tert-butoxycarbonylamino)nicotinates by treatment with LDA in THF.

PMID- 18610982
TI  - Understanding the behavior of N-tosyl and N-2-pyridylsulfonyl imines in CuII
      catalyzed aza-Friedel-Crafts reactions.
AB  - The different behavior of N-tosyl imines and N-(2-pyridyl)sulfonyl imines in Cu
      (II)-catalyzed AFCR is described. DFT theoretical calculations on the mode of
      coordination of the copper atom to both types of substrates allow understanding
      this different reactivity.

PMID- 18610983
TI  - Novel synthesis of cinnolines and 1-aminoindolines via Cu-catalyzed
      intramolecular N-arylation of hydrazines and hydrazones prepared from 3-haloaryl
      3-hydroxy-2-diazopropanoates.
AB  - A new and facile access to cinnolines, dihydrocinnolines, and 1-aminoindolines
      was established by use of diazo functionalities. The hydrazines and hydrazones as
      cyclization precursors derived from 3-haloaryl-3-hydroxy-2-diazopropanoates,
      which are prepared by one-pot procedure utilizing phase-transfer catalysis, are
      successfully converted to the corresponding nitrogen heterocycle by Cu-catalyzed
      N-arylation. Furthermore, analysis of UV spectra proved that 4-oxo-3-carboxylates
      predominantly exist not as 4-hydroxycinnoline (enol form) but as cinnolone (keto
      form).

PMID- 18610986
TI  - Superaligned carbon nanotube grid for high resolution transmission electron
      microscopy of nanomaterials.
AB  - Nano is one of the hottest topics in current science and technology.
      Characterizations of nanomaterials by high resolution transmission electron
      microscopy (TEM) are becoming indispensable today. To gain better performance of
      TEM, people are expecting a novel TEM grid of which the supporting film should be
      highly conductive, ultrathin but robust, and preferably nanoholey. Here we report
      a method of mass producing such a kind of carbon nanotube TEM grids. The
      supporting films are made by cross stacking ultrathin superaligned carbon
      nanotube films, resulting in a large number of nanosized holes and numerous
      effective edges. Together with the robustness, good conductivity, and strong
      adsorbability inherited from carbon nanotubes, these TEM grids show much better
      performance than conventional amorphous carbon grids.

PMID- 18610984
TI  - Solid-phase synthesis of alpha-glucosamine sulfoforms with fragmentation analysis
      by tandem mass spectrometry.
AB  - Sulfated epitopes of alpha-glucosamine (GlcN sulfoforms) were prepared by solid
      phase synthesis as models of internal glucosamines within heparan sulfate. An
      orthogonally protected 2'-hydroxyethyl GlcN derivative was immobilized on a
      trityl resin support and subjected to regioselective deprotection and sulfonation
      conditions, which were optimized with the aid of on-resin infrared or Raman
      analysis. The sulfoforms were cleaved from the resin under mild Lewis acid
      conditions without affecting the O- or N-sulfate groups and purified by reversed
      phase high-performance liquid chromatography (HPLC). The alpha-GlcN sulfoforms
      and their 4- O-benzyl ethers were examined by electrospray ionization tandem mass
      spectrometry (ESI-MS/MS), with product ion spectra produced by collision-induced
      dissociation (CID). ESI-MS/MS revealed significant differences in parent ion
      stabilities and fragmentation rates as a function of sulfate position. Ion
      fragmentation by CID resulted in characteristic mass losses with strong
      correlation to the positions of both free hydroxyl groups and sulfate ions. Most
      of these fragmentation patterns are consonant with elimination pathways, and
      suggest possible strategies for elucidating the structures of glucosamine-derived
      sulfoforms with identical m/ z ratios. In particular, fragmentation analysis can
      easily distinguish GlcN sulfoforms bearing the relatively rare 3- O-sulfate from
      isomers with the more common 6- O-sulfate.

PMID- 18610985
TI  - Effect of PIP2 binding on the membrane docking geometry of PKC alpha C2 domain:
      an EPR site-directed spin-labeling and relaxation study.
AB  - Protein kinase C isoform alpha (PKCalpha) is a ubiquitous, conventional PKC
      enzyme that possesses a conserved C2 domain. Upon activation by cytoplasmic Ca
      (2+) ions, the C2 domain specifically binds to the plasma membrane inner leaflet
      where it recognizes the target lipids phosphatidylserine (PS) and
      phosphatidylinositol-4,5-bisphosphate (PIP 2). The membrane penetration depth and
      docking angle of the membrane-associated C2 domain is not well understood. The
      present study employs EPR site-directed spin labeling and relaxation methods to
      generate a medium-resolution model of the PKCalpha C2 domain docked to a membrane
      of lipid composition similar to the plasma membrane inner leaflet. The approach
      measures EPR depth parameters for 10 function-retaining spin labels coupled to
      the C2 domain, and for spin labels coupled to depth calibration molecules. The
      resulting depth parameters, together with the known structure of the free C2
      domain, provide a sufficient number of constraints to define two membrane docking
      geometries for C2 domain bound to physiological membranes lacking or containing
      PIP 2, respectively. In both the absence and presence of PIP 2, the two bound Ca
      (2+) ions of the C2 domain lie near the anionic phosphate plane in the headgroup
      region, consistent with the known ability of the Ca (2+) and membrane-binding
      loops (CMBLs) to bind the headgroup of the PS target lipid. In the absence of PIP
      2, the polybasic lipid binding site on the beta3-beta4 hairpin is occupied with
      PS, but in the presence of PIP 2 this larger, higher affinity target lipid
      competitively displaces PS and causes the long axis of the domain to tilt 40 +/-
      10 degrees toward the bilayer normal. The ability of the beta3-beta4 hairpin site
      to bind PS as well as PIP 2 extends the lifetime of the membrane-docked state and
      is predicted to enhance the kinase turnover number of PKCalpha during a single
      membrane docking event. In principle, PIP 2-induced tilting of the C2 domain
      could modulate the activity of membrane-docked PKCalpha as it diffuses between
      membrane regions with different local PS and PIP 2 concentrations. Finally, the
      results demonstrate that EPR relaxation methods are sufficiently sensitive to
      detect signaling-induced changes in the membrane docking geometries of peripheral
      membrane proteins.

PMID- 18610987
TI  - Expedient vapor probing of organic amines using fluorescent nanofibers fabricated
      from an n-type organic semiconductor.
AB  - A new type of fluorescence sensory material with high sensitivity, selectivity,
      and photostability has been developed for vapor probing of organic amines. The
      sensory material is primarily based on well-defined nanofibers fabricated from an
      n-type organic semiconductor molecule, N-(1-hexylheptyl)perylene-3,4,9,10
      tetracarboxyl-3,4-anhydride-9,10-imide. Upon deposition onto a substrate, the
      entangled nanofibers form a meshlike, highly porous film, which enables expedient
      diffusion of gaseous analyte molecules within the film matrix, leading to
      milliseconds response for the vapor sensing.

PMID- 18610988
TI  - Near-field optical phase antennas for long-range plasmon coupling.
AB  - Plasmon-mediated long-range coupling of optical excitations is shown to be
      attainable using near-field phase antennas involving nanoparticles situated at
      focal spots. The antennas rely on metal-surface features that are geometrically
      arranged to produce constructive interference of plasmons emanating from a source
      spot over a designated image position. Large image-field intensities and focal
      spots as narrow as one-third of the wavelength are obtained for source-image
      separations of tens of micrometers. The ability to strongly couple distant focal
      spots through phase accumulation produced by engineered plasmon scatterers opens
      up a vast range of possibilities in contactless plasmon sensing, optical
      interconnects, and microscopy.

PMID- 18610989
TI  - Computational chemistry of modified [MFe3S4] and [M2Fe2S4] clusters: assessment
      of trends in electronic structure and properties.
AB  - The aim of this work is to understand the molecular evolution of iron-sulfur
      clusters in terms of electronic structure and function. Metal-substituted models
      of biological [Fe(4)S(4)] clusters in oxidation states [M(x)Fe(4
      x)S(4)](3+/2+/1+) have been studied by density functional theory (M = Cr, Mn, Fe,
      Co, Ni, Cu, Zn, and Pd, with x = 1 or 2). Most of these clusters have not been
      characterized before. For those that have been characterized experimentally, very
      good agreement is obtained, implying that also the predicted structures and
      properties of new clusters are accurate. Mean absolute errors are 0.024 A for
      bond lengths ([Fe(4)S(4)], [NiFe(3)S(4)], [CoFe(3)S(4)]) and 0.09 V for shifts in
      reduction potentials relative to the [Fe(4)S(4)] cluster. All structures form
      cuboidal geometries similar to the all-iron clusters, except the Pd-substituted
      clusters, which instead form highly distorted trigonal and tetragonal local sites
      in compromised, pseudocuboidal geometries. In contrast to other electron-transfer
      sites, cytochromes, blue copper proteins, and smaller iron-sulfur clusters, we
      find that the [Fe(4)S(4)] clusters are very insensitive to metal substitution,
      displaying quite small changes in reorganization energies and reduction
      potentials upon substitution. Thus, the [Fe(4)S(4)] clusters have an evolutionary
      advantage in being robust to pollution from other metals, still retaining
      function. We analyze in detail the electronic structure of individual clusters
      and rationalize spin couplings and redox activity. Often, several configurations
      are very close in energy, implying possible use as spin-crossover systems, and
      spin states are predicted accurately in all but one case ([CuFe(3)S(4)]). The
      results are anticipated to be helpful in defining new molecular systems with
      catalytic and magnetic properties.

PMID- 18610990
TI  - First principles study of the reaction of formic and acetic acids with hydroxyl
      radicals.
AB  - The oxidation of formic and acetic acids with hydroxyl radicals was studied as a
      model for the oxidation of larger carboxylic acids using first principles
      calculations. For formic acid, the CBS-QB3 activation barriers of 14.1 and 12.4
      kJ/mol for the acid and for the formyl channel, respectively, are within 3 kJ/mol
      of benchmark W1U values. Tunneling significantly enhances the rate coefficient
      for the acid channel and is responsible for the dominance of the acid channel at
      298 K. At 298 K, tunneling correction factors of 339 and 2.0 were calculated for
      the acid and the formyl channel using the small-curvature tunneling method and
      the CBS-QB3 potential energy surface. The Wigner, Eckart, and zero-curvature
      tunneling methods severely underestimate the importance of tunneling for the acid
      channel. The resulting reaction rate coefficient of 0.98 x 10(5) m(3)/(mol x s)
      at 298 K is within a factor 2-3 of experimental values. For acetic acid, an
      activation barrier of 11.0 kJ/mol and a tunneling correction factor of 199 were
      calculated for the acid channel. Two mechanisms compete for hydrogen abstraction
      at the methyl group, with activation barriers of 11.9 and 12.5 kJ/mol and
      tunneling correction factors of 9.1 and 4.1 at 298 K. The resulting rate
      coefficient of 1.2 x 10(5) m(3)/(mol x s) at 298 K and branching ratio of 94%
      compare well with experimental data.

PMID- 18610991
TI  - Nonradiative deexcitation dynamics of 9H-adenine: an OM2 surface hopping study.
AB  - The nonradiative relaxation of 9H-adenine was studied at the semiempirical OM2/MR
      CI level using the surface-hopping approach. Geometry optimizations of energy
      minima and conical intersections as well as single-point calculations of
      excitation energies at critical points were performed to characterize the
      relevant potential energy surfaces of 9H-adenine and to assess the accuracy of
      the OM2 results. Surface-hopping calculations were performed to describe the
      nonradiative dynamics of 9H-adenine after vertical excitation into the optically
      active state. They showed that the deexcitation process is mainly governed by a
      two-step relaxation consisting of an ultrashort component and a longer component.
      These findings compare well with experimental results from time-resolved
      photoelectron spectroscopy.

PMID- 18610992
TI  - Reactions of actinide metal atoms with ethane: computation and observation of new
      Th and U ethylidene dihydride, metallacyclopropane dihydride, and vinyl metal
      trihydride complexes.
AB  - A combined computational and experimental investigation provides evidence that
      excited thorium and uranium atoms activate ethane to form the vinyl metal
      trihydride, metallacyclopropane dihydride, and ethylidene metal dihydride for
      thorium and the latter complex and the inserted ethyl metal hydride for uranium.
      These products are trapped in solid argon and identified through deuterium
      isotopic substitution and vibrational frequencies calculated by density
      functional theory. Comparisons are made with group 4 and methane reaction
      products. Numerous calculations using several methods show that these simple
      ethylidene complexes are more distorted by the agostic interaction than the
      corresponding methylidene species. This enhanced agostic interaction probably
      arises from methyl hydrogen to alpha-H repulsions, which leads to a substantial
      decrease in the alpha-H to Th agostic interaction distance, and contributes to
      our understanding of agostic distortion in organometallic complexes.

PMID- 18610993
TI  - Energies, stability and structure properties of radicals derived from organic
      sulfides containing an acetyl group after the *OH attack: ab initio and DFT
      calculations vs experiment.
AB  - The mutual location of the sulfur atom and the acetyl group was found to affect
      significantly the (*)OH-induced oxidation mechanism of the organic sulfides
      containing either an alpha- or beta-positioned acetyl group. This phenomenon was
      reflected in formation of different intermediate products observed in pulse
      radiolysis experiments (Varmenot et al. J. Phys. Chem. A. 2004, 108, 6331-6346).
      In order to obtain a better support for the earlier interpretation of the
      experimental data, quantum mechanical calculations were performed using a density
      functional theory method (DFT-B3LYP) and the ab initio method (Moller-Plesset
      perturbation theory MP2) for optimizations and energy calculations of the parent
      molecules and radicals and radical cations derived from them. In accordance with
      experiments, it was found that the alpha-positioned acetyl group in S
      ethylthioacetate (SETAc) destabilizes hydroxysulfuranyl radicals and monomeric
      sulfur radical cations. Instead, formation of stable C-centered radicals of the
      alpha-(alkylthio)alkyl-type was found energetically favorable, the H3C-(*)CH-S
      C(=O)CH3 radical, in particular. On the other hand, the beta-positioned acetyl
      group in S-ethylthioacetone (SETA) does not destabilize hydroxysulfuranyl
      radicals, monomeric sulfur radical cations, and dimeric sulfur radical cations.
      Moreover, the alpha-(alkylthio)alkyl radicals of the type -S-(*)CH-C(=O)- were
      found to be particularly stabilized. The calculated transition states pointed
      toward the efficient direct conversion of the hydroxysulfuranyl radicals derived
      from SETAC and SETA radicals into the respective C-centered radicals. This
      reaction pathway, important in neutral solutions, is responsible for the absence
      of the dimeric radical cations of SETAc at low and high concentrations and of the
      dimeric radical cations of SETA at relatively low concentrations of the solute.

PMID- 18610995
TI  - Asymmetric synthesis of 2,3-dihydro-2-arylquinazolin-4-ones: methodology and
      application to a potent fluorescent tubulin inhibitor with anticancer activity.
AB  - For several decades the 2,3-dihydroquinazolinone (DHQZ) heterocycle has been
      known to possess a variety of important biological and medicinal properties.
      Despite the many interesting facets of these molecules, synthetic access to
      nonracemic DHQZ analogues has remained elusive. Herein, we disclose a synthetic
      route that allows access to either enantiomer of a variety of DHQZ derivatives.
      We illustrate the utility of this chemistry with the asymmetric preparation and
      biological evaluation of a new chiral fluorescent tubulin binding agent with
      extremely potent antiproliferative properties against human cancer cells. A
      computational rationale for the increased potency of the (S)-enantiomer over the
      (R)-enantiomer is given, based on the crystal structure of alpha,beta-tubulin
      complexed with colchicine. Taking advantage of the inherent fluorescence of these
      molecules, confocal images of GMC-5-193 (compound 7) in the cytoplasm of human
      melanoma cells (MDA-MB-435) cells are presented.

PMID- 18610997
TI  - The structural basis for peptidomimetic inhibition of eukaryotic ribonucleotide
      reductase: a conformationally flexible pharmacophore.
AB  - Eukaryotic ribonucleotide reductase (RR) catalyzes nucleoside diphosphate
      conversion to deoxynucleoside diphosphate. Crucial for rapidly dividing cells, RR
      is a target for cancer therapy. RR activity requires formation of a complex
      between subunits R1 and R2 in which the R2 C-terminal peptide binds to R1. Here
      we report crystal structures of heterocomplexes containing mammalian R2 C
      terminal heptapeptide, P7 (Ac-1FTLDADF7) and its peptidomimetic P6
      (1Fmoc(Me)PhgLDChaDF7) bound to Saccharomyces cerevisiae R1 (ScR1). P7 and P6,
      both of which inhibit ScRR, each bind at two contiguous sites containing residues
      that are highly conserved among eukaryotes. Such binding is quite distinct from
      that reported for prokaryotes. The Fmoc group in P6 peptide makes several
      hydrophobic interactions that contribute to its enhanced potency in binding to
      ScR1. Combining all of our results, we observe three distinct conformations for
      peptide binding to ScR1. These structures provide pharmacophores for designing
      highly potent nonpeptide class I RR inhibitors.

PMID- 18610998
TI  - Design, synthesis, and biological evaluation of antiviral agents targeting
      flavivirus envelope proteins.
AB  - Flavivirus envelope proteins (E proteins) have been shown to play a pivotal role
      in virus assembly, morphogenesis, and infection of host cells. Inhibition of
      flavivirus infection of a host cell by means of a small molecule envelope protein
      antagonist is an attractive strategy for the development of antiviral agents.
      Virtual screening of the NCI chemical database using the dengue virus envelope
      protein structure revealed several hypothetical hit compounds. Bioassay results
      identified a class of thiazole compounds with antiviral potency in cell-based
      assays. Modification of these lead compounds led to a series of analogues with
      improved antiviral activity and decreased cytotoxicity. The most active compounds
      11 and 36 were effective in the low micromolar concentration range in a cellular
      assay system.

PMID- 18611002
TI  - Synthesis and structures of selected triazapentadienate of Li, Mn, Fe, Co, Ni,
      Cu(I), and Cu(II) using 2,4-N,N'-disubstituted 1,3,5-triazapentadienate anions as
      ancillary ligands: [N(Ar)C(NMe2)NC(NMe2)N(R)](-) (Ar = Ph, 2,6-(i)Pr2-C6H3; R =
      H, SiMe3).
AB  - Addition reaction of ArN(SiMe 3)M (Ar = Ph or 2,6 - (i) Pr 2-C 6H 3 (Dipp); M =
      Li or Na) to 2 equivalents of alpha-hydrogen-free nitrile RCN (R = dimethylamido)
      gave the dimeric [M{N(Ar)C(NMe 2)NC(NMe 2)N(SiMe 3)}] 2 ( 1a, Ar = Ph, M = Li;
      1b, Ar = Ph, M = Na; 1c, Ar = Dipp, M = Li). 1d was obtained by hydrolysis of 1c
      at ambient temperature. Treatment of a double ratio of 1a or 1b with anhydrous
      MCl 2 (M = Mn, Fe, Co) yielded the 1,3,5-triazapentadienato complexes
      [M{N(Ph)C(NMe 2)NC(NMe 2)N(SiMe 3)} 2] (M = Mn, 2; Fe, 3; Co, 4) and with NiCl
      2.6H 2O gave [M{N(Ph)C(NMe 2)NC(NMe 2)N(H)} 2] (M = Ni, 5). Treatment of an equiv
      of 1c with anhydrous CuCl in situ and in air led to complexes [{N(Dipp)C(NMe
      2)NC(NMe 2)N(SiMe 3)}CuPPh 3] 6 and [Cu{N(Dipp)C(NMe 2)NC(NMe 2)N(H)} 2] 7,
      respectively. 1c, 1d, and 2- 7 were characterized by X-ray crystallography and
      microanalysis. 1c, 1d, 5, and 6 were well characterized by (1)H, (13)C NMR, 1c by
      (7)Li, and 6 by (31)P NMR as well. The structural features of these complexes
      were described in detail.

PMID- 18610999
TI  - Naturally occurring homoisoflavonoids function as potent protein tyrosine kinase
      inhibitors by c-Src-based high-throughput screening.
AB  - Protein tyrosine kinase (PTK) inhibitors represent emerging therapeutics for
      cancer chemoprevention. In our study, hematoxylin (26) was identified as one of
      the most remarkable c-Src inhibitors in an orthogonal compound-mixing library
      (32200 compounds) by using an ELISA-based automated high-throughput screening
      (HTS) strategy. Interestingly, hematoxylin was found to be an ATP competitive
      broad-spectrum PTK inhibitor in vitro, with IC50 values ranging from nanomolar to
      micromolar level. Further studies showed that such inhibition was associated with
      the PTK phosphorylation and subsequent downstream signaling pathways. The
      structure-activity relationship assessment of the PTK inhibitory potency of
      hematoxylin analogues isolated from Heamatoxylon campechianum was in good
      agreement with the result of concurrent molecular docking simulation: the
      catechol moiety in ring A and the hematoxylin-like three-dimensional structure
      were essential for c-Src-targeted activities. Hematoxylin and its natural
      analogues were substantially validated to function as a new class of PTK
      inhibitors.

PMID- 18611003
TI  - Comparison of mass spectrometry and other techniques for probing interactions
      between metal complexes and DNA.
AB  - Electrospray ionization mass spectrometry (ESI-MS) was used to study the binding
      interactions of two series of ruthenium complexes, [Ru(phen) 2L] (2+) and [RuL'
      2(dpqC)] (2+), to a double stranded DNA hexadecamer, and derive orders of
      relative binding affinity. These were shown to be in good agreement with orders
      of relative binding affinity derived from absorption and circular dichroism (CD)
      spectroscopic examination of the same systems and from DNA melting curves.
      However, the extent of luminescence enhancement caused by the addition of DNA to
      solutions of the ruthenium complexes showed little correlation with orders of
      binding affinity derived from ESI-MS or any of the other techniques. Overall the
      results provide support for the validity of using ESI-MS to investigate non
      covalent interactions between metal complexes and DNA.

PMID- 18611004
TI  - Density functional theory studies of spin, charge, and orbital ordering in
      YBaT2O5 (T = Mn, Fe, Co).
AB  - Spin, charge, and orbital orderings are influenced by electron/hole doping,
      cation radii, oxygen stoichiometry, temperature, magnetic field, and so on. In
      order to understand the role of electron/hole doping, we have studied variations
      in spin, charge, and orbital ordering in terms of d-band filling for YBaT 2O 5 (T
      = Mn, Fe, Co). The calculations were performed using density functional theory as
      implemented in the full-potential linearized augmented-plane-wave method. We have
      carried out calculations for nonmagnetic, ferromagnetic, and antiferromagnetic
      configurations. A ferrimagnetic ground state was established for YBaMn 2O 5,
      whereas YBaFe 2O 5 and YBaCo 2O 5 have antiferromagnetic ground states; all of
      these results are in agreement with experimental findings. The effects of spin
      orbit coupling, the Hubbard U parameter, and orbital polarization on the magnetic
      properties were also analyzed. The electronic band characteristics were analyzed
      using total as well as site- and orbital-projected densities of states. Inclusion
      of spin-orbit coupling and Coulomb correlation effects in the calculations was
      found to be important in order to reproduce the experimentally established
      semiconducting behaviors of YBaFe 2O 5 and YBaCo 2O 5. In order to quantify the
      charges at each atomic site, we made use of the Bader "atom-in-molecule" concept
      and Born effective-charge (BEC) analyses. The structural optimizations and BEC
      tensor calculations were performed using the VASP-PAW method. The different types
      of charge and orbital orderings in these compounds were visualized using the
      energy-projected density matrices of the d electrons. Substantial differences in
      ordering patterns with respect to d-band filling emerged. Ordering of the d z (2)
      orbital of Mn in YBaMn 2O 5 gave rise to G-type ferrimagnetic spin ordering along
      the c direction and checkerboard-type charge ordering, whereas ordering of the d
      x (2) - y (2) orbital of Fe in YBaFe 2O 5 caused Wollan-Koehler G-type
      antiferromagnetic spin ordering along the b direction and stripe-type charge
      ordering. Similarly, a complex pattern of orbital ordering in YBaCo 2O 5
      activated spin and charge orderings similar to those in YBaFe 2O 5.

PMID- 18611005
TI  - Magnetic nanoparticle-peptide conjugates for in vitro and in vivo targeting and
      extraction of cancer cells.
AB  - Magnetic cobalt spinel ferrite nanoparticles coated with biocompatible
      polygalacturonic acid were functionalized with ligands specific for targeting
      expressed EphA2 receptors on ovarian cancer cells. By using such magnetic
      nanoparticle-peptide conjugates, targeting and extraction of malignant cells were
      achieved with a magnetic field. Targeting ovarian cancer cells with receptor
      specific peptide-modified magnetic nanoparticles resulted in cell capture from a
      flow stream in vitro and from the peritoneal cavity of mice in vivo. Successful
      removal of metastatic cancer cells from the abdominal cavity and circulation
      using magnetic nanoparticle conjugates indicate the feasibility of a dialysis
      like treatment and may improve long-term survival rates of ovarian cancer
      patients. This approach can be applied for fighting other cancers, such as
      leukemia, once the receptors on malignant cells are identified and the efficacy
      of targeting ligands is established.

PMID- 18611006
TI  - Hydrogen adsorption in a highly stable porous rare-earth metal-organic framework:
      sorption properties and neutron diffraction studies.
AB  - A highly stable porous lanthanide metal-organic framework, Y(BTC)(H2O).4.3H2O
      (BTC = 1,3,5-benzenetricarboxylate), with pore size of 5.8 A has been constructed
      and investigated for hydrogen storage. Gas sorption measurements show that this
      porous MOF exhibits highly selective sorption behaviors of hydrogen over nitrogen
      gas molecules and can take up hydrogen of about 2.1 wt % at 77 K and 10 bar.
      Difference Fourier analysis of neutron powder diffraction data revealed four
      distinct D2 sites that are progressively filled within the nanoporous framework.
      Interestingly, the strongest adsorption sites identified are associated with the
      aromatic organic linkers rather than the open metal sites, as occurred in
      previously reported MOFs. Our results provide for the first time direct
      structural evidence demonstrating that optimal pore size (around 6 A, twice the
      kinetic diameter of hydrogen) strengthens the interactions between H2 molecules
      and pore walls and increases the heat of adsorption, which thus allows for
      enhancing hydrogen adsorption from the interaction between hydrogen molecules
      with the pore walls rather than with the normally stronger adsorption sites (the
      open metal sites) within the framework. At high concentration H2 loadings (5.5 H2
      molecules (3.7 wt %) per Y(BTC) formula), H2 molecules form highly symmetric
      novel nanoclusters with relatively short H2-H2 distances compared to solid H2.
      These observations are important and hold the key to optimizing this new class of
      rare metal-organic framework (RMOF) materials for practical hydrogen storage
      applications.

PMID- 18611007
TI  - New nucleotide pairs for stable DNA triplexes stabilized by stacking interaction.
AB  - New nucleotide pairs applicable to formation of DNA triplexes were developed. We
      designed oligonucleotides incorporating 5-aryl deoxycytidine derivatives (dC5Ars)
      and cyclic deoxycytidine derivatives, dCPPP and dCPPI, having an expanded
      aromatic area, as the second strand. As pairing partners, two types of abasic
      residues (C3: propylene linker, phi: abasic base) were chosen. It was concluded
      that, when the 5-aryl-modified cytosine bases paired with the abasic sites in
      TFOs in a space-fitting manner, the stability of the resulting triplexes
      significantly increased. The recognition of C3 toward dC5Ars was selective
      because of the stacking interactions between their aromatic part and the
      nucleobases flanking the abasic site. These results indicate the potential
      utility of new nucleotide triplets for DNA triplex formation, which might expand
      the variety of structures and sequences and might be useful for biorelated fields
      such as DNA nanotechnologies.

PMID- 18611008
TI  - Controllable redox reaction of chemically purified DNA-single walled carbon
      nanotube hybrids with hydrogen peroxide.
AB  - We report for the first time the controllable redox reaction of chemically
      purified ssDNA-HiPco SWNT hybrids with hydrogen peroxide. Compared with the
      suspensions before separation, the purified SWNT suspensions become inert with
      hydrogen peroxide which may serve as a platform for further chemical
      manipulation. In the presence of thiocyanate ions, the reaction of SWNTs with
      hydrogen peroxide is initiated and accelerated at the earlier reaction stage,
      accompanied with the near-infrared spectral suppression. At the later stage, the
      suppressed spectral intensity is recovered overtime. The thiocyanate ions may
      work as a mediator being able to control the reaction rate as well as the tunable
      properties of the reaction. The tunable redox reaction of SWNTs and H2O2 mediated
      by thiocyanate ions may offer a new sensing scheme for continuously monitoring
      H2O2 concentrations.

PMID- 18611009
TI  - On the molecular mechanism of drug intercalation into DNA: a simulation study of
      the intercalation pathway, free energy, and DNA structural changes.
AB  - Intercalation into DNA (insertion between a pair of base pairs) is a critical
      step in the function of many anticancer drugs. Despite its importance, a detailed
      mechanistic understanding of this process at the molecular level is lacking. We
      have constructed, using extensive atomistic computer simulations and umbrella
      sampling techniques, a free energy landscape for the intercalation of the
      anticancer drug daunomycin into a twelve base pair B-DNA. A similar free energy
      landscape has been constructed for a probable intermediate DNA minor groove-bound
      state. These allow a molecular level understanding of aspects of the
      thermodynamics, DNA structural changes, and kinetic pathways of the intercalation
      process. Key DNA structural changes involve opening the future intercalation site
      base pairs toward the minor groove (positive roll), followed by an increase in
      the rise, accompanied by hydrogen bonding changes of the minor groove waters. The
      calculated intercalation free energy change is -12.3 kcal/mol, in reasonable
      agreement with the experimental estimate -9.4 kcal/mol. The results point to a
      mechanism in which the drug first binds to the minor groove and then intercalates
      into the DNA in an activated process, which is found to be in general agreement
      with experimental kinetic results.

PMID- 18611011
TI  - Biomimetic synthesis of resorcylate natural products utilizing late stage
      aromatization: concise total syntheses of the marine antifungal agents 15G256iota
      and 15G256beta.
AB  - Diketo-1,3-dioxin-2-ones underwent retro-Diels-Alder reaction on heating in
      toluene at 110 degrees C to generate alpha,gamma,-triketo-ketenes. These were
      trapped with alcohols to provide 2,4,6-triketocarboxylates, which were smoothly
      aromatized by sequential reaction with potassium carbonate and methanolic
      hydrogen chloride to give resorcylate esters. The reaction was applied in the
      total synthesis of the marine antifungal agents 15G256beta (1), 15G256iota (2),
      and 15G256pi (3) and the mycotoxin S-(-)-zearalenone (4).

PMID- 18611010
TI  - Ultrafast excited-state dynamics of nanoscale near-infrared emissive
      polymersomes.
AB  - Formed through cooperative self-assembly of amphiphilic diblock copolymers and
      electronically conjugated porphyrinic near-infrared (NIR) fluorophores (NIRFs),
      NIR-emissive polymersomes (50 nm to 50 microm diameter polymer vesicles) define a
      family of organic-based, soft-matter structures that are ideally suited for deep
      tissue optical imaging and sensitive diagnostic applications. Here, we describe
      magic angle and polarized pump-probe spectroscopic experiments that: (i) probe
      polymersome structure and NIRF organization and (ii) connect emitter structural
      properties and NIRF loading with vesicle emissive output at the nanoscale. Within
      polymersome membrane environments, long polymer chains constrain ethyne-bridged
      oligo(porphinato)zinc(II) based supermolecular fluorophore (PZn n ) conformeric
      populations and disperse these PZn n species within the hydrophobic bilayer.
      Ultrafast excited-state transient absorption and anisotropy dynamical studies of
      NIR-emissive polymersomes, in which the PZn n fluorophore loading per nanoscale
      vesicle is varied between 0.1-10 mol %, enable the exploration of concentration
      dependent mechanisms for nonradiative excited-state decay. These experiments
      correlate fluorophore structure with its gross spatial arrangement within
      specific nanodomains of these nanoparticles and reveal how compartmentalization
      of fluorophores within reduced effective dispersion volumes impacts bulk
      photophysical properties. As these factors play key roles in determining the
      energy transfer dynamics between dispersed fluorophores, this work underscores
      that strategies that modulate fluorophore and polymer structure to optimize
      dispersion volume in bilayered nanoscale vesicular environments will further
      enhance the emissive properties of these sensitive nanoscale probes.

PMID- 18611013
TI  - Formation of tricyclic [4.3.3.0] adducts between 8-oxoguanosine and tyrosine
      under conditions of oxidative DNA-protein cross-linking.
AB  - 8-Oxo-7,8-dihydro-2'-deoxyguanosine (OG), a prevalent product of oxidative stress
      on cellular DNA, is readily further oxidized forming adducts with nucleophiles.
      In the presence of tyrosine or p-cresol, an unusual tricyclo[4.3.3.0] adduct has
      been characterized in both nucleoside and oligodeoxynucleotide studies. The
      adduct is more stable in oligomers than nucleosides and undergoes slow reversion
      and hydration to spiroiminodihydantoin.

PMID- 18611014
TI  - Complexes of borane and N-heterocyclic carbenes: a new class of radical hydrogen
      atom donor.
AB  - Calculations suggest that complexes of borane with N-heterocyclic carbenes (NHC)
      have B-H bond dissocation energies more then 20 kcal/mol less than free borane,
      diborane, borane-THF, and related complexes. Values are in the range of popular
      radical hydrogen atom donors like tin hydrides (70-80 kcal/mol). The resulting
      prediction that NHC borane complexes could be used as radical hydrogen atom
      donors was verified by radical deoxygenations of xanthates by using either AIBN
      or triethylborane as initiator.

PMID- 18611016
TI  - Protein-matrix coupling/uncoupling in "dry" systems of photosynthetic reaction
      center embedded in trehalose/sucrose: the origin of trehalose peculiarity.
AB  - Trehalose is a nonreducing disaccharide of glucose found in organisms, which can
      survive adverse conditions such as extreme drought and high temperatures.
      Furthermore, isolated structures, as enzymes or liposomes, embedded in trehalose
      are preserved against stressing conditions [see, e.g., Crowe, L. M. Comp.
      Biochem. Physiol. A 2002, 131, 505-513]. Among other hypotheses, such protective
      effect has been suggested to stem, in the case of proteins, from the formation of
      a water-mediated, hydrogen bond network, which anchors the protein surface to the
      water-sugar matrix, thus coupling the internal degrees of freedom of the
      biomolecule to those of the surroundings [Giuffrida, S.; et al. J. Phys. Chem. B
      2003, 107, 13211-13217]. Analogous protective effect is also accomplished by
      other saccharides, although with a lower efficiency. Here, we studied the
      recombination kinetics of the primary, light-induced charge separated state
      (P(+)Q(A)(-)) and the thermal stability of the photosynthetic reaction center
      (RC) of Rhodobacter sphaeroides in trehalose-water and in sucrose-water matrixes
      of decreasing water content. Our data show that, in sucrose, at variance with
      trehalose, the system undergoes a "nanophase separation" when the water/sugar
      mole fraction is lower than the threshold level approximately 0.8. We rationalize
      this result assuming that the hydrogen bond network, which anchors the RC surface
      to its surrounding, is formed in trehalose but not in sucrose. We suggest that
      both the couplings, in the case of trehalose, and the nanophase separation, in
      the case of sucrose, start at low water content when the components of the system
      enter in competition for the residual water.

PMID- 18611015
TI  - Biomolecular engineering by combinatorial design and high-throughput screening:
      small, soluble peptides that permeabilize membranes.
AB  - Rational design and engineering of membrane-active peptides remains a largely
      unsatisfied goal. We have hypothesized that this is due, in part, to the fact
      that some membrane activities, such as permeabilization, are not dependent on
      specific amino acid sequences or specific three-dimensional peptide structures.
      Instead they depend on interfacial activity: the ability of a molecule to
      partition into the membrane-water interface and to alter the packing and
      organization of lipids. Here we test that idea by taking a nonclassical approach
      to biomolecular engineering and design of membrane-active peptides. A 16,384
      member rational combinatorial peptide library, containing peptides of 9-15 amino
      acids in length, was screened for soluble members that permeabilize phospholipid
      membranes. A stringent, two-phase, high-throughput screen was used to identify 10
      unique peptides that had potent membrane-permeabilizing activity but were also
      water soluble. These rare and uniquely active peptides do not share any
      particular sequence motif, peptide length, or net charge, but instead they share
      common compositional features, secondary structure, and core hydrophobicity. We
      show that they function by a common mechanism that depends mostly on interfacial
      activity and leads to transient pore formation. We demonstrate here that
      composition-space peptide libraries coupled with function-based high-throughput
      screens can lead to the discovery of diverse, soluble, and highly potent membrane
      permeabilizing peptides.

PMID- 18611017
TI  - Surface-tuned assembly of porphyrin coordination oligomers.
AB  - Two self-complementary phenanthroline-strapped porphyrins bearing imidazole arms
      and C 12 or C 18 alkyl chains were synthesized, and their surface self-assembly
      was investigated by atomic force microscopy (AFM) on mica and highly ordered
      pyrrolitic graphite (HOPG). Upon zinc(II) complexation, stable porphyrin dimers
      formed, as confirmed by DOSY (1)H NMR and UV-visible spectroscopy. In solution,
      the dimers formed J-aggregates. AFM studies of the solutions dip-coated onto mica
      or drop-casted onto HOPG revealed that the morphologies of the assemblies formed
      were surface-tuned. On mica, fiber-like assemblies of short stacks of J
      aggregates were observed. The strong influence of the mica's epitaxy on the
      orientation of the fibers suggested a surface-assisted assembly process. On HOPG,
      interactions between the alkyl chains and the graphite surface resulted in the
      stabilization and trapping of monomer species followed by their subsequent
      association into coordination polymers on the surface. Interdigitation of the
      alkyl chains of separate polymer strands induced lateral association of wires to
      form islands that grew preferentially upon drop-casting and slow evaporation.
      Clusters of laterally assembled wires were observed for the more mobile
      functionalized porphyrins bearing C 12 chains.

PMID- 18611018
TI  - Synthesis of octacarboxy spherosilicate.
AB  - feasible new preparation was reported for an octacarboxylphenyl functionalized
      spherosilicate, octakis[(pcarboxyphenyl) dimethylsilyl]silicate, which was a
      versatile monomer leading to other functional spherosilicate derivatives. The
      synthesis was started from octakis[dimethyl(p-methylphenyl)silyl]silicate.
      Octakis[dimethyl(pmethylphenyl) silyl]silicate was brominated by NBS to produce
      octakis[dimethyl(4-tribromomethylphenyl)silyl]silicate. Finally,
      octakis[dimethyl(4-tribromomethylphenyl)silyl]silicate was hydrolyzed in the
      presence of AgNO3 and formic acid to give the desired compound.
      Octakis[(pcarboxyphenyl) dimethylsilyl]silicate was fully characterized by FTIR,
      1H NMR, 13C NMR, 29Si NMR spectra, ESI-MS, and elemental analysis.

PMID- 18611020
TI  - Designed supramolecular assembly of hydrogen-bonded anionic rosette layers.
AB  - Self-assembly of five two-dimensional hydrogen-bonded honeycomb grids bearing the
      rosette motif has been conducted with the guanidinium cation and various anionic
      components as the building blocks, tetraalkylammonium ions being employed as the
      interlayer templates. The sinusoidal supramolecular guanidinium-carbonate (1:1)
      rosette layer reported previously has been induced to adopt a nearly planar
      configuration using 1H-imidazole-4,5-dicarboxylate as an auxiliary template and
      spacer. A novel three-component guanidinium-boric acid-carbonate (1:2:1) wavy
      layer has been constructed, which features two distinguishable rosette motifs.
      Deviating from conventional topological design, the generation of new rosette
      layers, albeit highly distorted, has also been accomplished with guanidinium ions
      and anionic building blocks (1,2-dithiosquarate and dianionic form of 1,1'
      biphenyl-2,2',6,6'-tetracarboxylate) that do not conform to C3-symmetry.

PMID- 18611019
TI  - Effect of base stacking on the acid-base properties of the adenine cation radical
      [A*+] in solution: ESR and DFT studies.
AB  - In this study, the acid-base properties of the adenine cation radical are
      investigated by means of experiment and theory. Adenine cation radical (A*(+)) is
      produced by one-electron oxidation of dAdo and of the stacked DNA-oligomer (dA)6
      by Cl2*(-) in aqueous glass (7.5 M LiCl in H2O and in D2O) and investigated by
      ESR spectroscopy. Theoretical calculations and deuterium substitution at C8-H and
      N6-H in dAdo aid in our assignments of structure. We find the pKa value of A*(+)
      in this system to be ca. 8 at 150 K in seeming contradiction to the accepted
      value of < or = 1 at ambient temperature. However, upon thermal annealing to > or
      = 160 K, complete deprotonation of A*(+) occurs in dAdo in these glassy systems
      even at pH ca. 3. A*(+) found in (dA)6 at 150 K also deprotonates on thermal
      annealing. The stability of A*(+) at 150 K in these systems is attributed to
      charge delocalization between stacked bases. Theoretical calculations at various
      levels (DFT B3LYP/6-31G*, MPWB95, and HF-MP2) predict binding energies for the
      adenine stacked dimer cation radical of 12 to 16 kcal/mol. Further DFT B3LYP/6
      31G* calculations predict that, in aqueous solution, monomeric A*(+) should
      deprotonate spontaneously (a predicted pKa of ca. -0.3 for A*(+)). However, the
      charge resonance stabilized dimer AA*(+) is predicted to result in a significant
      barrier to deprotonation and a calculated pKa of ca. 7 for the AA*(+) dimer which
      is 7 pH units higher than the monomer. These theoretical and experimental results
      suggest that A*(+) isolated in solution and A*(+) in adenine stacks have highly
      differing acid-base properties resulting from the stabilization induced by hole
      delocalization within adenine stacks.

PMID- 18611021
TI  - Inspection of the duality of a verdazyl-based radical in transition metal
      complexes: a pi* donor ligand and a magnetic partner.
AB  - The behavior of a verdazyl-based radical bound to open-shell transition metal
      ions in the structurally and magnetically characterized [M(hfac)2imvd(o)] (M =
      Mn, Ni; hfac = (1,1,1,5,5,5)hexafluoroacetylacetonate; imvd(o) = 3-(2'
      imidazolyl)-1,5-dimethyl-6-oxoverdazyl) complexes is rationalized using ab initio
      wave-function-based calculations analysis. The calculated exchange coupling
      constants J (H = -J(s(M) x s(imvd(o)); J(Mn)(calcd) = -63 cm(-1), J(Ni)(calcd) =
      205 cm(-1)) are in excellent agreement with the experimental ones (J(Mn)(exp) = 
      63 cm(-1), J(Ni)(exp) = 193 cm(-1)). Even though both rings are involved through
      the binding mode of the imvd(o) radical, the spin density remains essentially
      localized on the nitrogen-rich ring. The singularity stems from its bidentate
      coordinating character. The analysis of the correlated wave function suggests
      that the verdazyl-based radical acts as a pi* donor ligand which allows ligand-to
      metal charge transfer and excludes metal-to-ligand charge transfer. This reflects
      the weak covalent character of the M-imvd(o) pi coordination bond. From a
      magnetic point of view, the through-space exchange governs the ferromagnetic
      character in the Ni derivative up to 153 cm(-1) as expected from a description
      limited to the magnetic orbitals. Nevertheless, the CI expansion displays the
      participation of excited doublet and quartet states (spin polarization) on the
      verdazyl moiety which leads to a significant additional ferromagnetic
      contribution (52 cm(-1)). In the [Mn(hfac)2imvd(o)] analogue, the
      antiferromagnetic contribution arising from kinetic exchange is only one-third of
      the observed exchange coupling constant. It is necessary to introduce dynamical
      correlation effects to quantitatively recover the exchange interaction in this
      compound. Since the pi* donor and spin-polarized characters of the verdazyl
      moiety dominate over the negligible polarizability of the imidazole part, it is
      concluded that the noninnocent nature of the imvd(o) radical is held by the
      verdazyl ring part.

PMID- 18611022
TI  - The complex role of the triphenylmethyl motif in anticancer compounds.
AB  - Compounds incorporating the triphenylmethyl motif constitute an emerging family
      of potent anticancer agents. Although several small molecules containing this
      pharmacophore have now been identified, the mechanism of cell death induction for
      some of these compounds is unknown. In an effort to define their mechanism of
      action, and to distinguish subtypes within the group of compounds containing the
      triphenylmethyl moiety, we have created novel triphenylmethyl-containing small
      molecules and have evaluated them in a battery of biological assays. Here we show
      that several phosphonate and phosphonochloridates possessing the triphenylmethyl
      motif potently induce death of multiple cancer cell lines in culture. Further
      assays evaluating the ability to cause cell cycle arrest, inhibit tubulin
      polymerization, dissociate mitochondrial-bound hexokinase in cancer cells, and
      inhibit calcium-dependent potassium ion channels indicate that triphenylmethyl
      containing compounds can be placed into at least four distinct categories, each
      with a different mechanism of action.

PMID- 18611024
TI  - Isotope labeling studies on the formation of 5-(hydroxymethyl)-2-furaldehyde
      (HMF) from sucrose by pyrolysis-GC/MS.
AB  - Although it is generally assumed that the reactivity of sucrose, a nonreducing
      sugar, in the Maillard reaction is due to its hydrolysis into free glucose and
      fructose, however, no direct evidence has been provided for this pathway,
      especially in dry and high temperature systems. Using specifically (13)C-labeled
      sucrose at C-1 of the fructose moiety, HMF formation was studied at different
      temperatures. Under dry pyrolytic conditions and at temperatures above 250
      degrees C, 90% of HMF originated from fructose moiety and only 10% originated
      from glucose. Alternatively, when sucrose was refluxed in acidic methanol at 65
      degrees C, 100% of HMF was generated from the glucose moiety. Moreover, the
      relative efficiency of the known HMF precursor 3-deoxyglucosone to generate HMF
      was compared to that of glucose, fructose and sucrose. Glucose exhibited a much
      lower conversion rate than 3-deoxyglucosone, however, both fructose and sucrose
      showed much higher conversion rates than 3-deoxyglucosone thus precluding it as a
      major precursor of HMF in fructose and sucrose solutions. Based on the data
      generated, a mechanism of HMF formation from sucrose is proposed. According to
      this proposal sucrose degrades into glucose and a very reactive fructofuranosyl
      cation. In dry systems this cation can be effectively converted directly into
      HMF.

PMID- 18611025
TI  - Effects of cationic species on visual color formation in model Maillard reactions
      of pentose sugars and amino acids.
AB  - Effects of cationic species on Maillard browning were examined after heating (ca.
      100 degrees C) aqueous pH 7.2 buffered solutions of amino acids and pentose
      sugars. Metallic ions of Group I metals (Li, Na, K, Rb and Cs) produced a small
      increase in browning (A420), but somewhat greater effects were observed with ions
      of Group II metals Ca and Mg. Browning was suppressed by triethylammonium ion,
      but unaffected by a salt of the stronger base, guanidine. The quaternary amine
      salt choline chloride produced enhanced browning and served as a model for
      phospholipid involvement in Maillard reactions. With alpha,omega-diamino acids
      increases in browning were observed which related to lowered pK2 values resulting
      from positively charged omega-substituents in these molecules.

PMID- 18611026
TI  - DNA adducts as biomarkers for oxidative and genotoxic stress from pesticides in
      crop plants.
AB  - Plant studies have been carried out to identify the nature and extent of the
      formation of adducts with DNA bases when treated with pesticide formulations. DNA
      extracted from crop plants after treatment with pesticide formulations has
      yielded evidence of adduct formation. The extent of DNA modification has been
      established by (32)P postlabeling studies. The radiochromatograms from (32)P
      postlabeling of isolated plant DNA from grapes, bush beans, soybeans, pumpkins,
      and cucumbers show elevated adduct levels in treated vegetable plants as compared
      with untreated controls. A number of different adduct spots appear, likely
      indicating adduct formation with pesticide molecules or their metabolites. The
      DNA adducts from hexenal and 4-hydroxy-2-nonenal were clearly observed,
      indicating oxidative stress and lipid peroxidation in the plant.

PMID- 18611027
TI  - Enzyme immunoassay for mycophenolic acid in milk and cheese.
AB  - Mycophenolic acid (MPA) was reacted with N-hydroxysuccinimide and conjugated to
      keyhole limpet hemocyanin (KLH), and to horseradish peroxidase (HRP),
      respectively. The MPA-KLH was used to produce anti-MPA antiserum in rabbits. A
      competitive direct enzyme immunoassay (EIA) for MPA was established with anti-MPA
      antiserum and MPA-HRP conjugate. The mean 50% inhibition and detection limit of
      MPA standard curves (n = 103) were 197 +/- 67 and 81 +/- 48 pg/mL, respectively.
      The EIA was specific for MPA and its synthetic 2-morpholinoethyl ester,
      mycophenolate mofetil (91% relative cross-reactivity). Raw bulk milk and
      pasteurized milk, with and without beta-glucuronidase pretreatment, were analyzed
      by EIA. No MPA was found in milk, at a detection limit of 100 pg/mL (recovery 58
      66% at 0.125-2 ng/mL). Blue-veined cheese from the German market (n = 53) was
      analyzed by EIA, and the detection limit was at 0.5 ng/g (recovery 68-79% at 5
      100 ng/g). All but two cheeses contained MPA, although mostly (66%) at levels of
      <10 ng/g. MPA at 400-1200 ng/g was found in Roquefort cheeses. Highest levels (4
      11 microg/g) were found in a German soft cheese preparation. MPA levels in
      mycelium-rich parts of cheese were 3 times higher than in mycelium-free parts.

PMID- 18611028
TI  - Polyphenolic compounds and antioxidant activity of new and old apple varieties.
AB  - There is considerable evidence to show that a greater intake of apple contributes
      to improved health by reducing the risk of diseases, such as cardiovascular
      disease and some forms of cancer. Apple fruit is a major source of phenol
      compounds, because its consumption is widespread in many countries and it is
      available on the market for the whole year. The phenolic composition of 67
      varieties of apple cultivars (new and old varieties) was examined for the
      concentration of some important phytochemicals and antioxidant activity. For the
      first time, we have looked at the correlation and compared polyphenolic
      coumpounds in Golden Delicious variety and new varieties grown from it. Up to 18
      compounds, including catechin, procyanidin, hydroxycinnamates, flavonols,
      anthocyanins, and dihydrochalcones, were analyzed by high-performance liquid
      chromatography with diode array detection analysis of crude extracts and after
      thiolysis and LC-MS. The mean content of total polyphenols lay between 523.02 and
      2723.96 mg/100 g dw and depending upon the apples variety. Flavanols (catechin
      and oligomeric procyanidins) are the major class of apple polyphenols,
      representing more than 80%, followed by hydroxycinnamic acids (1-31%), flavonols
      (2-10%), dihydrochalcones (0.5-5%), and in red apples, anthocyanins (1%). In this
      study, the best correlation was found for the total polyphenols and ABTS method,
      with a lower correlation for FRAP and DPPH methods ( r = 0.871, 0.839, and 0.804,
      respectively). The presented data clearly demonstrated that new varieties, i.e.,
      Ozark Gold, Julyred, and Jester, of apple had the same or higher value of
      bioactive compounds in comparison to the old varieties, i.e., Golden Delicious,
      Idared, and Jonagold.

PMID- 18611029
TI  - Water uptake mechanism in crispy bread crust.
AB  - Crispness is an important quality characteristic of dry solid food products such
      as crispy rolls. Its retention is directly related to the kinetics of water
      uptake by the crust. In this study, a method for the evaluation of the water
      sorption kinetics in bread crust is proposed. Two different sorption experiments
      were used: an oscillatory sorption test and a sorption test in which the air
      relative humidity (RH) was increased stepwise. These two experiments had
      different time scales, which made it possible to get a better understanding of
      the mechanisms involved. Results show that the adsorption and desorption dynamics
      of the oscillatory sorption test could be described by a single exponential in
      time. The water uptake rate ( k) was one of the fitting parameters. A maximum in
      the water uptake rate was found for a RH value between 50 and 70%. The rate
      parameters of the experiment where RH was increased stepwise were around a factor
      10 lower than those derived from oscillatory sorption experiments. This is an
      important factor when designing experiments for the determination of water uptake
      rates. In addition, also a parameter describing the time dependence of the rate
      parameters of the oscillatory sorption experiment was calculated (C), again by
      fitting a single exponential to the rate parameters. C was in the same range as
      the rate parameter of the isotherm experiment. This indicates that different
      (relaxation) processes are acting at the same time in the bread crust during
      water uptake.

PMID- 18611030
TI  - Susceptibility of the tomato mutant high pigment-2dg (hp-2dg) to Orobanche spp.
      infection.
AB  - The consumption of natural products with potential health benefits has been
      continuously growing, and enhanced pigmentation is of major economic importance
      in fruits and vegetables. The tomato hp-2 ( dg ) is an important mutant line that
      has been introgressed into commercial tomato cultivars marketed as lycopene rich
      tomatoes (LRT) because of their enhanced fruit pigmentation, attributed to higher
      levels of carotenoids, including lycopene. Strigolactones are signaling compounds
      that mediate host finding in root parasitic plants and are biosynthetically
      derived from carotenoids. Considering the high carotenoid content of the hp-2 (
      dg ) mutant, we studied its susceptibility to the root parasite Orobanche. In a
      field experiment, the average number of Orobanche aegyptiaca plants growing on hp
      2 ( dg ) was surprisingly significantly reduced compared with its isogenic wild
      type counterpart. In vitro assays and LC-MS/MS analysis showed that this
      reduction was associated with a lower production of strigolactones, which
      apparently renders the high-carotenoid hp-2 ( dg ) mutant less susceptible to
      Orobanche.

PMID- 18611031
TI  - Water content or water activity: what rules crispy behavior in bread crust?
AB  - A dry crust loses its crispness when water migrates into the crust. It is not
      clear if it is the amount of water absorbed or the water activity ( a w) that
      leads to a loss of crispness. The hysteresis effect observed when recording a
      water sorption isotherm allowed us to study the effects of a w and moisture
      content separately. All experiments were carried out on model bread crusts made
      from Soissons bread flour. The effect of water content and water activity on the
      glass transition of model bread crusts was studied in detail using two
      complimentary techniques: phase transition analysis (PTA) and nuclear magnetic
      resonance (NMR). The results were compared with sensory data and results from a
      puncture test, which provided data on acoustic emission and fracture mechanics
      during breaking of the crusts. The water content of the crust was found to be
      decisive for the transition point as measured by PTA and NMR. However, both water
      content and water activity had an effect on perceived crispness and number of
      force and sound peaks. From this may be concluded that the distribution of the
      water in the samples with a history of high water content is more inhomogeneous,
      which results in crispy and less crispy regions, thus making them overall more
      crispy than samples with the same water content but higher a w.

PMID- 18611032
TI  - Phenoloxidase activity of hemocyanin in whiteleg shrimp Penaeus vannamei:
      conversion, characterization of catalytic properties, and role in postmortem
      melanosis.
AB  - Latent phenoloxidase activity of hemocyanin (Hc) in whiteleg shrimp Penaeus
      vannamei was assayed to determine its potential involvement in postmortem
      melanosis. Conversion of pure 12-mer, but not 6-mer, hemocyanin to phenoloxidase
      by endogenous (serine proteinases) and exogenous (SDS) effectors demonstrated the
      need of complex aggregation for displaying enzyme activity. Because Hc was
      converted to Hc-phenoloxidase (HcPO) by hemocytes extracts, the mechanism of
      conversion seems to be the same for polyphenoloxidases. HcPO has similar
      biochemical and kinetic properties as real polyphenoloxidases and uses mono- and
      diphenols as substrates. The kinetics of hydroxygenation of monophenols has a lag
      phase, typical for tyrosinases, contrary to oxidation of diphenols. Regardless of
      the structure of the substrate, melanin is finally formed. Because of the
      abundance, distribution, and resistance of Hc to freezing-thawing, involvement of
      Hc in black spot formation postmortem is suggested. This has important
      implications for commercialization of shrimp and related seafood.

PMID- 18611033
TI  - Studies toward frondosin A and its analogues. Formal total synthesis of (+/-)
      frondosin A.
AB  - Two reaction sequences commencing with different starting materials were
      successfully employed for the synthesis of frondosin A analogues, including (+/-)
      frondosin A dimethyl ether. Construction of the bicyclo[5.4.0]undecane core in
      each case was achieved through an expedient microwave-assisted tandem 5-exo
      cyclization--Claisen rearrangement process.

PMID- 18611034
TI  - Preparation of aryloxetanes and arylazetidines by use of an alkyl-aryl suzuki
      coupling.
AB  - The oxetan-3-yl and azetidin-3-yl substituents have previously been identified as
      privileged motifs within medicinal chemistry. An efficient approach to installing
      these two modules into aromatic systems, using a nickel-mediated alkyl-aryl
      Suzuki coupling, is presented.

PMID- 18611035
TI  - Stereo- and regiospecific cu-catalyzed cross-coupling reaction of vinyl iodides
      and thiols: a very mild and general route for the synthesis of vinyl sulfides.
AB  - A mild and efficient method for the copper-catalyzed formation of vinylic carbon
      sulfur bonds has been developed. The desired vinyl sulfides are obtained in good
      to excellent yields, with full retention of stereochemistry. This method is
      particularly noteworthy given its mild reaction conditions, simplicity, and
      generality, as well as low cost of the catalyst system.

PMID- 18611036
TI  - Comparative inhibition studies of enoyl-CoA hydratase 1 and enoyl-CoA hydratase 2
      in long-chain fatty acid oxidation.
AB  - Enoyl-CoA hydratase 1 and enoyl-CoA hydratase 2 in long-chain fatty acid
      oxidation were comparatively investigated through mechanistic studies for
      inactivation of the enzymes with methylenecyclopropylformyl-CoA and 3-octynoyl
      CoA. Methylenecyclopropylformyl-CoA can inactivate both enzymes, while 3-octynoyl
      CoA inactivates enoyl-CoA hydratase 2 only. The study increased our understanding
      of these two enzymes in fatty acid oxidation.

PMID- 18611037
TI  - Pharmacokinetics and biodistribution of nanoparticles.
AB  - Nanoparticles show their promise for improving the efficacy of drugs with a
      narrow therapeutic window or low bioavailability, such as anticancer drugs and
      nucleic acid-based drugs. The pharmacokinetics (PK) and tissue distribution of
      the nanoparticles largely define their therapeutic effect and toxicity. Chemical
      and physical properties of the nanoparticles, including size, surface charge, and
      surface chemistry, are important factors that determine their PK and
      biodistribution. The intracellular fate of the nanoparticles after cellular
      internalization that affects the drug bioavailability is also discussed.
      Strategies for overcoming barriers for intracellular delivery and drug release
      are presented. Finally, future directions for improving the PK of nanoparticles
      and perspectives in the field are discussed.

PMID- 18611038
TI  - Combating the threat of anthrax: a quantitative structure-activity relationship
      approach.
AB  - Bacterial agents or products more likely to be used as biological weapons of mass
      destruction are Bacillus anthracis, Francisella tularensis, Yersinia pestis, and
      the neurotoxin of Clostridium botulinum. Anthrax is an acute infectious disease
      with a high mortality rate caused by Bacillus anthracis, reinforcing the need for
      better adjunctive therapy and prevention strategies. In this paper, we developed
      7 QSAR models on penicillin-based inhibitors of the class A and B beta-lactamases
      from B. anthracis and inhibitors of anthrax lethal factor to understand the
      chemical-biological interactions. Hydrophobic and steric factors are found to be
      the most important determinants of the activity. Internal (cross-validation ( q
      (2)), quality factor ( Q), Fischer statistics ( F), and Y-randomization) and
      external validation tests have validated all the QSAR models.

PMID- 18611039
TI  - Density-viscosity product of small-volume ionic liquid samples using quartz
      crystal impedance analysis.
AB  - Quartz crystal impedance analysis has been developed as a technique to assess
      whether room-temperature ionic liquids are Newtonian fluids and as a small-volume
      method for determining the values of their viscosity-density product, rho eta.
      Changes in the impedance spectrum of a 5-MHz fundamental frequency quartz crystal
      induced by a water-miscible room-temperature ionic liquid, 1-butyl-3
      methylimiclazolium trifluoromethylsulfonate ([C4mim][OTf]), were measured. From
      coupled frequency shift and bandwidth changes as the concentration was varied
      from 0 to 100% ionic liquid, it was determined that this liquid provided a
      Newtonian response. A second water-immiscible ionic liquid, 1-butyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide [C4mim][NTf2], with
      concentration varied using methanol, was tested and also found to provide a
      Newtonian response. In both cases, the values of the square root of the viscosity
      density product deduced from the small-volume quartz crystal technique were
      consistent with those measured using a viscometer and density meter. The third
      harmonic of the crystal was found to provide the closest agreement between the
      two measurement methods; the pure ionic liquids had the largest difference of
      approximately 10%. In addition, 18 pure ionic liquids were tested, and for 11 of
      these, good-quality frequency shift and bandwidth data were obtained; these 12
      all had a Newtonian response. The frequency shift of the third harmonic was found
      to vary linearly with square root of viscosity-density product of the pure ionic
      liquids up to a value of square root(rho eta) approximately 18 kg m(-2) s(-1/2),
      but with a slope 10% smaller than that predicted by the Kanazawa and Gordon
      equation. It is envisaged that the quartz crystal technique could be used in a
      high-throughput microfluidic system for characterizing ionic liquids.

PMID- 18611040
TI  - Superparamagnetic maghemite nanorods: analysis by coupling field-flow
      fractionation and small-angle X-ray scattering.
AB  - We report on the online coupling of asymmetrical flow field-flow fractionation
      (A4F) with small-angle X-ray scattering (SAXS) for the detection of
      nanoparticles. The A4F was used to fractionate superparamagnetic maghemite
      nanoparticles, which were prepared continuously with a micromixer. The outlet of
      the A4F was directly coupled to a flow capillary of a SAXSess instrument (Kratky
      type of camera). SAXS curves were recorded in a 1 s time interval. This was
      possible by using intense synchrotron radiation. The radii of gyration of the
      nanoparticles, as determined from Guinier plots, increased from 2 to 6 nm with
      increasing fractionation time of the A4F. A more detailed analysis of the
      scattering curves revealed that the particles were cylindrical in shape
      (nanorods), which we attributed to the micromixing preparation technique. The
      radii of the nanorods increased only slightly from 1.2 to 1.7 nm with increasing
      fractionation time, while the lengths increased strongly from 7.0 to 30.0 nm. The
      volume distribution of the nanorods was determined and described by Schultz-Zimm
      and log-normal distributions. Nanorod volumes increased from 45 to 263 nm(3),
      corresponding to molar masses of 140 x 10(3) to 820 x 10(3) g mol(-1). We propose
      A4F-SAXS coupling as a new method for analysis of nanoparticles of complex
      composition in solution. It allows precise online determination of the particle's
      shape and size distributions. This method can be applied to mixtures of
      nanoparticles of arbitrary shapes and sizes (1-100 nm). Moreover, the total time
      needed for fractionation and online SAXS data recording is usually only 20 min.

PMID- 18611042
TI  - Analysis of the nucleation and growth of amorphous CaCO3 by means of time
      resolved static light scattering.
AB  - The formation of amorphous calcium carbonate particles from supersaturated
      aqueous solution is relevant to many processes in nature and industry. The
      present work introduces time-resolved static light scattering as a new tool to
      investigate the initial stage of this process. The process is initiated by mixing
      a solution of Na(2)CO(3) with a CaCl(2) solution or, alternatively, by mixing
      solutions of the dimethyl ester of carbonic acid and CaCl(2) with solutions of
      NaOH. Particle formation was analyzed by recording scattering curves as a
      function of time. Scattering data indicate the formation of compact spheres with
      diameters close to 360 nm. In the case of particle formation induced by ester
      hydrolysis, nucleation sets in after a certain lag time. Particle size is
      homogeneous, and the growth mechanism corresponds to an addition of ions or small
      constituent particles to a constant number of growing spheres. An increase of the
      NaOH concentration, which triggers ester hydrolysis, decreases the lag period
      prior to the onset of particle formation. An increase of the solution temperature
      also decreases this lag period. The temperature and NaOH dependent duration of
      the lag time could successfully be interpreted in terms of the kinetics of the
      ester hydrolysis. The work establishes time-resolved static light scattering as
      an efficient tool to investigate the particle formation process of amorphous
      calcium carbonate.

PMID- 18611041
TI  - Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium
      channel.
AB  - KCNE1 is a single-span membrane protein that modulates the voltage-gated
      potassium channel KCNQ1 (K V7.1) by slowing activation and enhancing channel
      conductance to generate the slow delayed rectifier current ( I Ks) that is
      critical for the repolarization phase of the cardiac action potential.
      Perturbation of channel function by inherited mutations in KCNE1 or KCNQ1 results
      in increased susceptibility to cardiac arrhythmias and sudden death with or
      without accompanying deafness. Here, we present the three-dimensional structure
      of KCNE1. The transmembrane domain (TMD) of KCNE1 is a curved alpha-helix and is
      flanked by intra- and extracellular domains comprised of alpha-helices joined by
      flexible linkers. Experimentally restrained docking of the KCNE1 TMD to a closed
      state model of KCNQ1 suggests that KCNE1 slows channel activation by sitting on
      and restricting the movement of the S4-S5 linker that connects the voltage sensor
      to the pore domain. We postulate that this is an adhesive interaction that must
      be disrupted before the channel can be opened in response to membrane
      depolarization. Docking to open KCNQ1 indicates that the extracellular end of the
      KCNE1 TMD forms an interface with an intersubunit cleft in the channel that is
      associated with most known gain-of-function disease mutations. Binding of KCNE1
      to this "gain-of-function cleft" may explain how it increases conductance and
      stabilizes the open state. These working models for the KCNE1-KCNQ1 complexes may
      be used to formulate testable hypotheses for the molecular bases of disease
      phenotypes associated with the dozens of known inherited mutations in KCNE1 and
      KCNQ1.

PMID- 18611043
TI  - Wetting and absorption of water drops on Nafion films.
AB  - Water drops on Nafion films caused the surface to switch from being hydrophobic
      to being hydrophilic. Contact angle hysteresis of >70 degrees between advancing
      and receding values were obtained by the Wilhelmy plate technique. Sessile drop
      measurements were consistent with the advancing contact angle; the sessile drop
      contact angle was 108 degrees . Water drop adhesion, as measured by the
      detachment angle on an inclined plane, showed much stronger water adhesion on
      Nafion than Teflon. Sessile water and methanol drops caused dry Nafion films to
      deflect. The flexure went through a maximum with time. Flexure increased with
      contact area of the drop, but was insensitive to the film thickness. Methanol
      drops spread more on Nafion and caused larger film flexure than water. The
      results suggest that the Nafion surface was initially hydrophobic but water and
      methanol drops caused hydrophilic sulfonic acid domains to be drawn to the Nafion
      surface. Local swelling of the film beneath the water drop caused the film to
      buckle. The maximum flexure is suggested to result from motion of a water
      swelling front through the Nafion film.

PMID- 18611044
TI  - Adsorptive separation of isobutene and isobutane on Cu3(BTC)2.
AB  - The metal organic framework material Cu3(BTC)2 (BTC = 1,3,5
      benzenetricarboxylate) has been synthesized using different routes: under
      solvothermal conditions in an autoclave, under atmospheric pressure and reflux,
      and by electrochemical reaction. Although the compounds display similar
      structural properties as evident from the powder X-ray diffraction (XRD)
      patterns, they differ largely in specific surface area and total pore volume.
      Thermogravimetric and chemical analysis support the assumption that pore blocking
      due to trimesic acid and/or methyltributylammoniummethylsulfate (MTBS) which has
      been captured in the pore system during reaction is a major problem for the
      electrochemically synthesized samples. Isobutane and isobutene adsorption has
      been studied for all samples at different temperatures in order to check the
      potential of Cu3(BTC)2 for the separation of small hydrocarbons. While the
      isobutene adsorption isotherms are of type I according to the IUPAC
      classification, the shape of the isobutane isotherm is markedly different and
      closer to type V. Adsorption experiments at different temperatures show that a
      somewhat higher amount of isobutene is adsorbed as compared to isobutane.
      Nevertheless, the differential enthalpies of adsorption are only different by
      about 5 kJ/mol, indicating that a strong interaction between the copper centers
      and isobutene does not drive the observed differences in adsorption capacity. The
      calculated breakthrough curves of isobutene and isobutane reveal that a low
      pressure separation is preferred due to the peculiar shape of the isobutane
      adsorption isotherms. This has been confirmed by preliminary breakthrough
      experiments using an equimolar mixture of isobutane and isobutene.

PMID- 18611045
TI  - In vivo tumor cell targeting with "click" nanoparticles.
AB  - The in vivo fate of nanomaterials strongly determines their biomedical efficacy.
      Accordingly, much effort has been invested into the development of library
      screening methods to select targeting ligands for a diversity of sites in vivo.
      Still, broad application of chemical and biological screens to the in vivo
      targeting of nanomaterials requires ligand attachment chemistries that are
      generalizable, efficient, covalent, orthogonal to diverse biochemical libraries,
      applicable under aqueous conditions, and stable in in vivo environments. To date,
      the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition or "click" reaction has
      shown considerable promise as a method for developing targeted nanomaterials in
      vitro. Here, we investigate the utility of "click" chemistry for the in vivo
      targeting of inorganic nanoparticles to tumors. We find that "click" chemistry
      allows cyclic LyP-1 targeting peptides to be specifically linked to azido
      nanoparticles and to direct their binding to p32-expressing tumor cells in vitro.
      Moreover, "click" nanoparticles are able to stably circulate for hours in vivo
      following intravenous administration (>5 h circulation time), extravasate into
      tumors, and penetrate the tumor interstitium to specifically bind p32-expressing
      cells in tumors. In the future, in vivo use of "click" nanomaterials should
      expedite the progression from ligand discovery to in vivo evaluation and
      diversify approaches toward multifunctional nanoparticle development.

PMID- 18611046
TI  - Peptide cysteine thiyl radicals abstract hydrogen atoms from surrounding amino
      acids: the photolysis of a cystine containing model peptide.
AB  - Peptide cysteine thiyl radicals were generated through UV-photolysis of disulfide
      precursors, in order to follow intramolecular reactions of those radicals with
      neighboring amino acids. When reactions were carried out in D(2)O, there was a
      significant incorporation of deuterium specifically into the C(alpha)-H bonds of
      glycine residues in positions i+1 and i-1 to the Cys residue, indicating a fast
      reversible H-atom transfer. This H-atom transfer occurred prior to the formation
      of final, nonradical products including free thiol, thioaldehyde, and aldehyde.
      Such fast H-atom transfer is relevant to biologic conditions of oxidative stress
      and to the stabilization of proteins against oxidation, where the formation of
      carbon-centered radicals in proteins may lead to fragmentation, intramolecular
      cross-linking, aggregation and/or epimerization.

PMID- 18611047
TI  - Phosphorylation of osteopontin is required for inhibition of calcium oxalate
      crystallization.
AB  - Under near-physiological pH, temperature, and ionic strength, a kinetics constant
      composition (CC) method was used to examine the roles of phosphorylation of a 14
      amino acid segment (DDVDDTDDSHQSDE) corresponding to potential crystal binding
      domains within the osteopontin (OPN) sequence. The phosphorylated 14-mer OPN
      peptide segment significantly inhibits both the nucleation and growth of calcium
      oxalate monohydrate (COM), inhibiting nucleation by markedly increasing induction
      times and delaying subsequent growth by at least 50% at concentrations less than
      44 nM. Molecular modeling predicts that the doubly phosphorylated peptide binds
      much more strongly to both (-101) and (010) faces of COM. The estimated binding
      energies are, in part, consistent with the CC experimental observations. Circular
      dichroism spectroscopy indicates that phosphorylation does not result in
      conformational changes in the secondary peptide structure, suggesting that the
      local binding of negatively charged phosphate side chains to crystal faces
      controls growth inhibition. These in vitro results reveal that the interactions
      between phosphorylated peptide and COM crystal faces are predominantly
      electrostatic, further supporting the importance of macromolecules rich in
      anionic side chains in the inhibition of kidney stone formation. In addition, the
      phosphorylation-deficient form of this segment fails to inhibit COM crystal
      growth up to concentrations of 1450 nM. However, at sufficiently high
      concentrations, this nonphosphorylated segment promotes COM nucleation. Dynamic
      light scattering (DLS) and small-angle X-ray scattering (SAXS) results confirm
      that aggregation of the nonphosphorylated peptide segment takes place in solution
      above 900 nM when the aggregated peptide particles may exceed a well-defined
      minimum size to be effective crystallization promoters.

PMID- 18611049
TI  - Synthesis, cytotoxicity, and antioxidative activity of minor prenylated chalcones
      from Humulus lupulus.
AB  - The minor hop ( Humulus lupulus) chalcones 3'-geranylchalconaringenin (3), 5'
      prenylxanthohumol (4), flavokawin (5), xanthohumol H (8), xanthohumol C (9), and
      1'',2''-dihydroxanthohumol C (10) were synthesized. The non-natural chalcones 3'
      geranyl-6'-O-methylchalconaringenin (2), 3'-methylflavokawin (6), and 2'-O-methyl
      3'-prenylchalconaringenin (7) were also synthesized. Cytotoxicity was
      investigated in HeLa cells, and these compounds all had IC 50 values comparable
      to xanthohumol (8.2-19.2 microM). The ORAC-fluorescein assay revealed potent
      antioxidative activity for 7 and 8 with 5.2 and 4.8 Trolox equivalents,
      respectively.

PMID- 18611048
TI  - Facile preparation of well-defined AB2 Y-shaped miktoarm star polypeptide
      copolymer via the combination of ring-opening polymerization and click chemistry.
AB  - Well-defined AB2 Y-shaped miktoarm star polypeptide copolymer, PZLL-b-(PBLG)2,
      was synthesized via a combination of ring-opening polymerization (ROP) of alpha
      amino acid N-carboxyanhydride (NCA) and click chemistry, where PZLL is
      poly(epsilon-benzyloxycarbonyl-L-lysine) and PBLG is poly(gamma-benzyl-L
      glutamate). First, two types of primary-amine-containing initiators, N-aminoethyl
      3,5-bis(propargyloxyl)-benzamide and 3-azidopropylamine, were synthesized and
      employed for the ROP of NCA, leading to the formation of dialkynyl-terminated
      PZLL and azide-terminated PBLG, dialkynyl-PZLL and PBLG-N3, respectively. The
      subsequent copper(I)-catalyzed cycloaddition reaction between dialkynyl-PZLL and
      slightly excess PBLG-N3 led to facile preparation of PZLL-b-(PBLG)2 Y-shaped
      miktoarm star polypeptide copolymer. The excess PBLG-N3 was scavenged off by
      reacting with alkynyl-functionalized Wang resin. The obtained Y-shaped miktoarm
      star polypeptide copolymer was characterized by gel permeation chromatograph
      (GPC), Fourier transform-infrared spectroscopy (FT-IR), and (1)H NMR. Moreover,
      after the hydrolysis of protecting benzyl and benzyloxycarbonyl groups of PZLL-b
      (PBLG)2, water-soluble pH-responsive Y-shaped miktoarm star polypeptide
      copolymer, PLL-b-(PLGA)2, was obtained, where PLL is poly(L-lysine) and PLGA is
      poly(L-glutamic acid). It can self-assemble into PLGA-core micelles at acidic pH
      and PLL-core micelles at alkaline pH, accompanied with the coil-to-helix
      transition of PLGA and PLL sequences, respectively. The spontaneous pH-responsive
      supramolecular assembly of PLL-b-(PLGA)2 miktoarm star polypeptide copolymer has
      been investigated via a combination of (1)H NMR, laser light scattering (LLS),
      transmission electron microscopy (TEM), and circular dichroism (CD) spectroscopy.

PMID- 18611050
TI  - Antimicrobial diterpenes from Trigonostemon chinensis.
AB  - Five new diterpenes, trigonochinenes A-E (1-5), and two known ones, 3,4- seco
      sonderianol (6) and 3,4- seco-sonderianic acid (7), were isolated from the aerial
      part of Trigonostemon chinensis. Compounds 1-4 possess a rare 3,4-seco
      cleistanthanic skeleton, and compound 5 is a highly aromatized tetranorditerpene.
      Structures of these compounds were elucidated by spectroscopic analysis. The
      antimicrobial activities of compounds 1-7 were evaluated against a panel of
      bacteria and fungi.

PMID- 18611051
TI  - Enantiospecific synthesis of (+)-alstonisine via a stereospecific osmylation
      process.
AB  - The first enantiospecific total synthesis of (+)-alstonisine has been
      accomplished from D-tryptophan methyl ester 13 in 12% overall yield (in 17
      reaction vessels). A diastereospecific osmylation process has been employed as a
      key step to convert indole 18 into spirocyclic oxindole 19. Mechanistic studies
      of the stereoselective osmylation of the 2,3-indole double bond of indole
      alkaloids has been carried out. Compelling evidence for the intramolecular
      delivery of OsO4 via N b-complexation was obtained for the osmylation process.
      The correct structure of (+)-alstonisine (1) was determined by NOE spectroscopic
      experiments and further confirmed by single-crystal X-ray analysis.

PMID- 18611052
TI  - Molecular clips with extended aromatic sidewalls as receptors for electron
      acceptor molecules. Synthesis and NMR, photophysical, and electrochemical
      properties.
AB  - We have synthesized molecular clips 1 comprising (i) two benzo[k]fluoranthene
      sidewalls and (ii) a dimethylene-connected benzene bridge that carries two
      acetoxy (1a), hydroxy (1b), or methoxy (1c) substituents in the para position.
      Their NMR spectra, single-crystal structures, and photophysical (fluorescence
      intensity, lifetime, depolarization) and electrochemical properties are
      discussed. For the purpose of comparison, similar compounds (2 and 3) containing
      only one benzo[k]fluoranthene unit have been prepared and studied. The strongly
      fluorescent clips 1 form stable complexes with electron-acceptor guests because
      of a highly negative electrostatic potential on the inner van der Waals surface
      of their cavity. The complexation constants in chloroform solution for a variety
      of guests, determined by NMR and fluorescence titration, are much larger than
      those of the corresponding anthracene and naphthalene clips (4 and 5),
      particularly in the case of extended aromatic guests. The effect of the
      substituents in the para position of the benzene spacer unit of clips 1 is
      discussed on the basis of the host-guest complex structures obtained by X-ray
      analysis and molecular mechanics simulations. In the case of 9-dicyanomethylene
      2,4,7-trinitrofluorene (TNF) guest, complex formation with clip 1a causes
      dramatic changes in the photophysical and electrochemical properties: (i) a new
      charge-transfer band at 600 nm arises, (ii) a very efficient quenching of the
      strong benzo[k]fluoranthene fluorescence takes place, (iii) shifts of both the
      first oxidation (clip-centered) and reduction (TNF-centered) potentials are
      observed, and (iv) reversible disassembling of the complex can be obtained by
      electrochemical stimulation.

PMID- 18611053
TI  - Silver-catalyzed C(sp)-H and C(sp)-Si bond transformations and related processes.

PMID- 18611054
TI  - Coinage metal-assisted synthesis of heterocycles.

PMID- 18611055
TI  - Preparation of a library of unsymmetrical ureas based on 8
      azabicyclo[3.2.1]octane scaffold.
AB  - This paper reports the preparation of a library of unsymmetrical ureas based on 8
      azabicyclo[3.2.1]octane scaffold. The reported synthetic route uses nortropane-8
      carbonyl chlorides as key intermediates that, when treated with a slight excess
      of amine, give the corresponding ureas in high yield (129 examples).

PMID- 18611056
TI  - Transfection ability and intracellular DNA pathway of nanostructured gene
      delivery systems.
AB  - Considerable efforts have been devoted to the design of structured materials with
      functional properties. Polyelectrolyte multilayer films are now a well
      established nanostructured concept with numerous potential applications, in
      particular as biomaterial coatings. This technique allows the preparation of
      nanostructured architectures exhibiting specific properties for cell-activation
      control and local drug delivery. In this study, we used a multilayered system
      made of poly-(l-lysine)/hyaluronic acid (PLL/HA) as a reservoir for active DNA
      complexes with nonviral gene-delivery vectors, PLL, beta-cyclodextrin (CD), and
      PLL-CD. When embedded into the multilayered films, the transfection efficiencies
      of the DNA complexes and the cell viability were improved. The highest
      transfection efficiency was obtained with the PLL-CD/plasmid DNA (pDNA)
      complexes. We found that this high transfection efficiency was related to an
      efficient internalization of the complexes in the cell cytoplasm and selected
      nuclei domains through a nonendocytotic pathway. For the first time, we report
      the intracellular pathway of the pDNA in complexes incorporated into the
      multilayered system.

PMID- 18611057
TI  - Time-resolved detection of single-electron interference.
AB  - We demonstrate real-time detection of self-interfering electrons in a double
      quantum dot embedded in an Aharonov-Bohm interferometer, with visibility
      approaching unity. We use a quantum point contact as a charge detector to perform
      time-resolved measurements of single-electron tunneling. With increased bias
      voltage, the quantum point contact exerts a back-action on the interferometer
      leading to decoherence. We attribute this to emission of radiation from the
      quantum point contact, which drives noncoherent electronic transitions in the
      quantum dots.

PMID- 18611058
TI  - Organelle-targeted nanocarriers: specific delivery of liposomal ceramide to
      mitochondria enhances its cytotoxicity in vitro and in vivo.
AB  - To further increase the therapeutic activity of drugs known to act on
      intracellular target sites, in vivo drug delivery approaches must actively
      mediate the specific delivery of drug molecules to the subcellular site of
      action. We show here that surface modification of nanocarriers with
      mitochondriotropic triphenylphosphonium cations facilitates the efficient
      subcellular delivery of a model drug to mitochondria of mammalian cells and
      improves its activity in vitro and in vivo.

PMID- 18611059
TI  - Chiral shells and achiral cores in CdS quantum dots.
AB  - We report and explain circular dichroism in semiconductor quantum dots. CdS
      nanocrystals capped with penicillamine enantiomers were prepared and found to be
      both highly luminescent and optically active. No new features in circular
      dichroism were observed as the nanocrystal grew larger. Density functional
      calculations reveal that penicillamine strongly distorts surface Cd, transmitting
      an enantiomeric structure to the surface layers and associated electronic states.
      The quantum dot core is found to remain undistorted and achiral.

PMID- 18611062
TI  - Effects of hepatic or renal impairment on the pharmacokinetics of aripiprazole.
AB  - BACKGROUND AND OBJECTIVES: Two studies were conducted to investigate whether the
      pharmacokinetics of the atypical antipsychotic aripiprazole were altered in
      individuals with hepatic or renal impairment compared with those with normal
      hepatic or renal function. STUDY DESIGN: Two open-label, single-dose studies.
      STUDY SETTING: Clinical research unit. PATIENTS: Study 1: Subjects with normal
      hepatic function (n = 6) and subjects with hepatic impairment (Child-Pugh class A
      [mild, n = 8], B [moderate, n = 8] or C [severe, n = 3]). Study 2: Subjects with
      normal renal function (creatinine clearance >80 mL/min; n = 7) and subjects with
      severe renal impairment (creatinine clearance <30 mL/min; n = 6). TREATMENT:
      Single oral dose of aripiprazole 15 mg. PHARMACOKINETIC ANALYSES:
      Noncompartmental pharmacokinetic analysis was performed using plasma aripiprazole
      and dehydro-aripiprazole concentration-time data. MAIN OUTCOME MEASURES: Study 1
      (hepatic impairment study): apparent oral clearance of unbound drug (CL/Fu) and
      the maximum plasma concentration (Cmax) of aripiprazole; Study 2 (renal
      impairment study): CL/Fu, Cmax and renal clearance (CL(R)). Safety assessments
      included 12-lead ECGs, vital sign monitoring, clinical laboratory measurements
      and assessment of adverse events.f RESULTS: In the hepatic impairment study, the
      mean total Cmax of aripiprazole was significantly lower in subjects with severe
      hepatic impairment compared with those with normal hepatic function (p = 0.04).
      The fraction of aripiprazole unbound (fu) was significantly greater for subjects
      with mild (p = 0.02) or severe hepatic impairment (p < 0.01) but not for those
      with moderate hepatic impairment (p = 0.09) compared with healthy controls. There
      were no meaningful differences in either the Cmax of unbound aripiprazole or
      CL/Fu between groups. The mean CL(R) of aripiprazole was negligible (0.04 mL/h/kg
      in controls and 0.19 mL/h/kg in patients with severe hepatic impairment). In the
      renal impairment study, the mean total Cmax values were numerically higher
      (approximately 40%) and the area under the plasma aripiprazole concentration-time
      curve from time zero to infinity was lower (approximately 19%) in renally
      impaired subjects versus those with normal renal function; the fu was comparable
      between groups. Aripiprazole CL(R) was approximately 3-fold higher in renally
      impaired subjects, but this difference was not statistically significant. No
      deaths or serious adverse events were reported during either study. CONCLUSION: A
      single aripiprazole 15-mg dose was well tolerated. There were no meaningful
      differences in aripiprazole pharmacokinetics between groups of subjects with
      normal hepatic or renal function and those with either hepatic or renal
      impairment. Adjustment of the aripiprazole dose does not appear to be required in
      populations with hepatic or renal impairment.

PMID- 18611061
TI  - Clinical pharmacokinetics and pharmacodynamics of aliskiren.
AB  - Aliskiren is the first orally bioavailable direct renin inhibitor approved for
      the treatment of hypertension. It acts at the point of activation of the renin
      angiotensin-aldosterone system, or renin system, inhibiting the conversion of
      angiotensinogen to angiotensin I by renin and thereby reducing the formation of
      angiotensin II by angiotensin-converting enzyme (ACE) and ACE-independent
      pathways. Aliskiren is a highly potent inhibitor of human renin in vitro
      (concentration of aliskiren that produces 50% inhibition of renin 0.6 nmol/L).
      Aliskiren is rapidly absorbed following oral administration, with maximum plasma
      concentrations reached within 1-3 hours. The absolute bioavailability of
      aliskiren is 2.6%. The binding of aliskiren to plasma proteins is moderate (47
      51%) and is independent of the concentration. Once absorbed, aliskiren is
      eliminated through the hepatobiliary route as unchanged drug and, to a lesser
      extent, through oxidative metabolism by cytochrome P450 (CYP) 3A4. Unchanged
      aliskiren accounts for approximately 80% of the drug in the plasma following oral
      administration, indicating low exposure to metabolites. The two major oxidized
      metabolites of aliskiren account for less than 5% of the drug in the plasma at
      the time of the maximum concentration. Aliskiren excretion is almost completely
      via the biliary/faecal route; 0.6% of the dose is recovered in the urine. Steady
      state plasma concentrations of aliskiren are reached after 7-8 days of once-daily
      dosing, and the accumulation factor for aliskiren is approximately 2. After
      reaching the peak, the aliskiren plasma concentration declines in a multiphasic
      fashion. No clinically relevant effects of gender or race on the pharmacokinetics
      of aliskiren are observed, and no adjustment of the initial aliskiren dose is
      required for elderly patients or for patients with renal or hepatic impairment.
      Aliskiren showed no clinically significant increases in exposure during
      coadministration with a wide range of potential concomitant medications, although
      increases in exposure were observed with P-glycoprotein inhibitors. Aliskiren
      does not inhibit or induce CYP isoenzyme or P-glycoprotein activity, although
      aliskiren is a substrate for P-glycoprotein, which contributes to its relatively
      low bioavailability. Aliskiren is approved for the treatment of hypertension at
      once-daily doses of 150 mg and 300 mg. Phase II and III clinical studies
      involving over 12,000 patients with hypertension have demonstrated that aliskiren
      provides effective long-term blood pressure (BP) lowering with a good safety and
      tolerability profile at these doses. Aliskiren inhibits plasma renin activity
      (PRA) by up to 80% following both single and multiple oral-dose administration.
      Similar reductions in PRA are observed when aliskiren is administered in
      combination with agents that alone increase PRA, including diuretics
      (hydrochlorothiazide, furosemide [frusemide]), ACE inhibitors (ramipril) and
      angiotensin receptor blockers (valsartan), despite greater increases in the
      plasma renin concentration. Moreover, PRA inhibition and BP reductions persist
      for 2-4 weeks after stopping treatment, which is likely to be of benefit in
      patients with hypertension who occasionally miss a dose of medication.
      Preliminary data on the antiproteinuric effects of aliskiren in type 2 diabetes
      mellitus suggest that renoprotective effects beyond BP lowering may be possible.
      Further studies to evaluate the effects of aliskiren on cardiovascular outcomes
      and target organ protection are ongoing and will provide important new data on
      the role of direct renin inhibition in the management of hypertension and other
      cardiovascular disease.

PMID- 18611063
TI  - A model of the kinetics of lanthanum in human bone, using data collected during
      the clinical development of the phosphate binder lanthanum carbonate.
AB  - OBJECTIVE: Lanthanum carbonate (Fosrenol) is a non-calcium phosphate binder that
      controls hyperphosphataemia without increasing calcium intake above guideline
      targets. The biological fate and bone load of lanthanum were modelled with the
      aid of a four-compartment kinetic model, analogous to that of calcium. METHODS:
      The model used data from healthy subjects who received intravenous lanthanum
      chloride or oral lanthanum carbonate, and bone lanthanum concentration data
      collected from dialysis patients during three long-term trials (up to 5 years).
      RESULTS: Infusion of lanthanum chloride or ingestion of lanthanum carbonate led
      to a rapid rise in plasma lanthanum concentrations, followed by an exponential
      decrease. Comparison of oral and intravenous exposure confirmed that lanthanum is
      very poorly absorbed. On a typical intake of lanthanum (3000 mg/day as lanthanum
      carbonate), the rate of absorption was calculated as 2.2 microg/h, with a urinary
      excretion rate constant of 0.004-0.01 h(-1). The faecal content of endogenous
      lanthanum was estimated to be 8- to 20-fold greater than that of urine, compared
      with a ratio of only about 1 for calcium. The model predicts that upon multiple
      dosing, plasma lanthanum concentrations rise rapidly to a near plateau and then
      increase by about 3% per year. However, this small change is obscured by the
      variability of the study data, which show that a plateau is rapidly attained by 2
      weeks and is thereafter maintained for at least 2 years. The initial deposition
      rate of lanthanum in bone was 1 microg/g/year and, after 10 years of lanthanum
      carbonate treatment, the model predicts a 7-fold increase in total bone lanthanum
      (from 10 mg to 69 mg [from 1 microg/g wet weight to 6.6 microg/g wet weight]),
      with lanthanum cleared after cessation of treatment at 13% per year. The model
      indicates that lanthanum flow from bone surface to bone interior is much lower
      than that of calcium. CONCLUSION: Bone is the major reservoir for metals, but
      bone lanthanum concentrations are predicted to remain low after long-term
      treatment because of very poor intestinal absorption.

PMID- 18611064
TI  - Pro-angiogenic cytokines as cardiovascular therapeutics: assessing the potential.
AB  - Coronary artery and peripheral vascular disease are global health concerns with
      limited therapies. Currently available medical and surgical therapies for these
      disease processes are highly effective for only a fraction of patients. Extensive
      effort has been devoted to finding molecular therapies to enhance perfusion and
      function of ischemic myocardial and peripheral skeletal muscle. Angiogenic
      cytokines (fibroblast growth factor [FGF], vascular endothelial growth factor
      [VEGF], hepatocyte growth factor [HGF], placental growth factor, stromal cell
      derived factor-1alpha) have shown theoretical and experimental promise in
      upregulating endogenous endothelial progenitor cell-mediated angiogenesis.
      Preliminary clinical trials have suggested improvements in myocardial and
      peripheral perfusion following therapy with FGF, VEGF, and HGF. Further studies
      on the efficacy of cytokine-mediated angiogenesis are required before widespread
      clinical application is possible. Investigation into adjunctive cytokine
      therapies for myocardial and peripheral muscle ischemia is warranted. Based on
      experimental evidence, appropriate angiogenic cytokine therapy should provide
      benefits in both perfusion and hemodynamic function.

PMID- 18611065
TI  - Strategies toward the improved oral delivery of insulin nanoparticles via
      gastrointestinal uptake and translocation.
AB  - The design of strategies that improve the absorption of insulin through the
      gastrointestinal tract is a considerable challenge in the pharmaceutical sciences
      and would significantly enhance the treatment of diabetes mellitus. Several
      strategies have been devised to overcome physiologic and morphologic barriers to
      insulin absorption, including the inhibition of acidic and enzymatic degradation,
      enhancement of membrane permeability or widening of tight junctions, chemical
      modification of insulin, and the formulation of carrier systems. In particular,
      the concept of nanoparticulate carriers for oral insulin delivery has evolved
      through remarkable advances in nanotechnology. Investigations focused on uptake
      and translocation via Peyer's patches have demonstrated high levels of
      nanoparticle absorption based on significant alterations in the glycemic response
      to various glucogenic sources. This paper reviews the mechanisms for insulin and
      particle uptake and translocation through the gastrointestinal tract, and the
      potential barriers to this, outlines the design of nanoparticulate carriers for
      the oral delivery of insulin, and presents prospects for its clinical
      application.

PMID- 18611060
TI  - Population pharmacokinetics and pharmacodynamics for treatment optimization in
      clinical oncology.
AB  - Population pharmacokinetic and pharmacodynamic analysis is an important tool to
      support optimal treatment in clinical oncology. The population approach is
      suitable to explain variability between patients and to establish relationships
      between drug exposure and a relevant pharmacodynamic parameter. This can
      facilitate the selection of dosing schedules, the development of strategies for
      dose individualization and the application of therapeutic drug monitoring of
      anticancer agents. This review discusses the role of population pharmacokinetics
      and pharmacodynamics in clinical oncology to enhance the efficiency of drug
      development and to support the development of safe and effective dosing regimens
      for optimal treatment of cancer patients. An overview of published population
      studies of investigational anticancer agents and established treatment regimens
      is presented.

PMID- 18611066
TI  - B-cell-targeted therapy for systemic lupus erythematosus: an update.
AB  - Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized
      by a myriad of immune system aberrations, most likely resulting from pathogenic
      autoantibody production, immune complex deposition, and subsequent end-organ
      damage. B cells play a key role in the pathogenesis; therefore, B-cell-targeted
      therapies, including B-cell depletion and blockage of B-cell survival factors
      such as B-lymphocyte stimulator (BLyS), are potential therapeutic targets for
      SLE. In uncontrolled clinical trials from approximately 20 studies, rituximab--a
      mouse-human chimeric anti-CD20 monoclonal antibody that effectively depletes B
      cells--has been demonstrated to reduce disease activity and decrease serum
      autoantibodies, with a clinical response of 86% in a case series of approximately
      400 SLE patients with refractory disease, with or without concomitant use of
      cyclophosphamide. Epratuzumab, a humanized anti-CD22 monoclonal antibody that
      partially depletes B cells, has also been shown to reduce disease activity but
      not to decrease autoantibody levels in patients with moderately active SLE.
      Randomized controlled phase I/II trials in patients with active SLE have
      documented that belimumab, a humanized anti-BLyS monoclonal antibody, reduces B
      cell numbers, inhibits disease activity and decreases anti-double-stranded DNA
      autoantibody in SLE patients. All these therapies are well tolerated, but
      accompanying infectious complications have been observed. Other B-cell-targeted
      therapies such as 'humanized' monoclonal antibodies to CD20 (e.g. ocrelizumab)
      and agents that interrupt B-cell/T-cell interactions also have potential, and the
      efficacy of these, along with rituximab, belimumab and epratuzumab, needs to be
      determined by randomized controlled trials.

PMID- 18611067
TI  - Long-acting GLP-1 analogs for the treatment of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is characterized by insulin resistance, impaired glucose
      induced insulin secretion, and inappropriately elevated glucagon levels which
      eventually result in hyperglycemia. The currently available treatment modalities
      for type 2 diabetes are often unsatisfactory in getting patients to glycemic
      goals, even when used in combination, and therefore many patients develop
      microvascular and macrovascular diabetic complications. Additionally, these
      treatment modalities are often limited by inconvenient dosage regimens and safety
      and tolerability issues, the latter including hypoglycemia, bodyweight gain,
      edema, and gastrointestinal intolerance. There is, therefore, a need for new and
      more efficacious agents, targeting not only treatment, but also prevention of the
      disease, its progression, and its associated complications. Recently, an entirely
      new therapeutic option for the treatment of type 2 diabetes has become available
      in the US (since October 2005) and in Europe (since May 2007): the incretin-based
      therapies. The incretin-based therapies fall into two different classes: (i)
      incretin mimetics, i.e. injectable peptide preparations with actions similar to
      the natural incretin hormones; and (ii) the incretin enhancers, i.e. orally
      available agents that inhibit the degradation of the incretin hormones in the
      body and thereby increase their plasma levels and biologic actions. This article
      focuses on the incretin mimetics and outlines the scientific basis for the
      development of glucagon-like peptide-1 (GLP-1) analogs, reviews clinical
      experience gained so far, and discusses future expectations for long-acting forms
      of GLP-1 analogs.

PMID- 18611068
TI  - Anti-adhesion molecule strategies for Crohn disease.
AB  - The last few years have been highlighted by further knowledge and optimism
      regarding the use of biologic therapy in Crohn disease. The introduction of anti
      tumor necrosis factor (TNF) therapy into clinical practice in the form of the
      murine chimeric monoclonal antibody infliximab, and more recently the fully human
      monoclonal antibody adalimumab, has significantly advanced treatment for Crohn
      disease. Despite the introduction of the anti-TNF agents, 20-40% of patients will
      fail to respond to initial induction therapy, and of the initial responders only
      60-70% will have a sustained response at 1 year. Therefore, there remains a
      significant unmet need in the treatment of patients with Crohn disease. A novel
      approach in suppressing inflammation is to intervene in the mechanisms
      responsible for the migration of leukocytes into inflamed tissue. One such method
      is by selective adhesion molecule inhibition. Several agents based on this
      strategy have been evaluated in the treatment of inflammatory bowel disease. It
      is expected that these agents will offer an alternative to the anti-TNF agent
      class in patients with moderate to severe Crohn disease.

PMID- 18611070
TI  - Spotlight on lanreotide Autogel in acromegaly.
AB  - Lanreotide Autogel (ATG) [Somatuline Depot]The use of trade names is for product
      identification purposes only and does not imply endorsement. is a novel, long
      acting preparation of the somatostatin analog lanreotide acetate that acts via
      somatostatin receptors to reduce both growth hormone (GH) and insulin-like growth
      factor-I (IGF-I) levels. It is indicated for the management of acromegaly and,
      relative to most other licensed agents, it has a favorable pharmacokinetic
      profile that permits administration once every 28-42 days. Subcutaneous
      lanreotide ATG was an effective and generally well tolerated treatment in
      patients with acromegaly in well designed trials and extension studies of up to 4
      years' duration. It was shown to be no less effective than intramuscular
      lanreotide long-acting (LA) microparticle treatment in these studies, with more
      limited data showing that lanreotide ATG therapy was as effective as
      intramuscular octreotide long-acting repeating (octreotide LAR) treatment. While
      both of these latter agents offer the advantage of treatment once every 28 days,
      lanreotide ATG also has the advantage of being available in a convenient pre
      filled syringe and is given subcutaneously rather than intramuscularly like other
      somatostatin analogs. Thus it provides a valuable first-line option for the
      management of patients with acromegaly.

PMID- 18611069
TI  - Autologous T-cell vaccination for multiple sclerosis: a perspective on progress.
AB  - T-cell vaccination (TCV) is a unique approach to induce immune regulation that
      may have importance in the treatment of autoimmune diseases, including multiple
      sclerosis (MS). TCV employs a classic vaccine strategy of injecting an attenuated
      form of the disease-causing agent--in this case, myelin-reactive T cells--that
      have been selected and expanded from each MS donor and then re-injected after
      irradiation to induce protective immunity. This anti-T-cell immunity consistently
      results in selective deletion or regulation of the targeted pathogenic T cells in
      vivo. Longitudinal studies have established that TCV is safe and often results in
      a reduced relapse rate and clinical stability or improvement, at least
      temporarily, in the majority of treated MS patients. These results lend direct
      support to the involvement of inflammatory myelin-reactive T cells in the MS
      disease process. However, these hopeful trends reported in a number of pilot
      trials await validation in larger proof-of-principle trials that are now in
      progress.

PMID- 18611071
TI  - [Ethical principles in research related to regenerative therapy].
AB  - Recently published data on the function and properties of stem cells are examined
      and analyzed. This knowledge enhances our understanding of human development:
      stem cells follow a precise hierarchical pattern both in time and space, and they
      are part of the symbiosis of fetus and mother. The data do not support the idea
      of the existence of an early stage of the embryo development lacking a personal
      character. It has been suggested that an early embryo lacks an entity of
      sufficient ontological autonomy, which would be acquired with organogenesis at
      later stages. It is an ethical commitment of the scientific community to provide
      serious and precise information about the advances, problems and solutions
      involved an regenerative therapy. The use of autologous or heterologous human
      cells in this field demands of rules which determine their use and commercial
      potential. The induced reprogramming of adult cells to an embryonic stage (iPS)
      opens up new important perspectives both in basic research and for clinical
      treatments. The ethical commitment of Yamanaka, developer of this technology,
      with regard to its use in clinical treatments, is an example of the researcher's
      responsibility of the researcher, and, at the same time, an illustration of how
      that science may render a service to mankind only through ethical principles.

PMID- 18611072
TI  - [Living, life and quality of life].
AB  - Human life and quality of life are approached unitarily from their common root in
      living person, since only the person can claim them as rights and observe them as
      duties. The passage from the natural inclination to live towards the moral order
      is fulfilled from the ethical-ontological bridge-concept of human dignity. The
      absolute character of dignity means that life appears in the ethical realm as a
      duty prior to a right, both with regard to its care by the subject itself and its
      respect by others. This right-duty extends from life to the quality of life,
      since the living person always has a margin between personal living and the vital
      achievements it is capable of: this margin must be respected and promoted.

PMID- 18611073
TI  - [Misunderstandings on concepts life and quality of life].
AB  - The rationale of this work is to indicate some of the ethical and anthropological
      conceptions that, to my understanding, underlie present day medicine when more
      relevance is granted to the quality of life than to life itself.

PMID- 18611074
TI  - [Is autonomy ground of human dignity?].
AB  - This paper considers the conditions of autonomy if this is to be the foundation
      of human dignity. Since Kant Modernity has dissociated nature from morality and
      has tried to support autonomy in its purely formal aspect. To forget nature has
      voluntarist consequences that affect the way in which autonomy is understand. But
      autonomy does not consist of not having links, but of knowing how to assume one's
      own links freely and to be conscious of one's own limits. Autonomy and liberty
      are the very thing of the rational being, capable of discerning good and bad, and
      this must direct our actions. Reason directs as and distances us from reality to
      recognize the advisable thing in the human being.

PMID- 18611075
TI  - [Dignity and autonomy in North American bioethics].
AB  - Bioethics needs an inherent concept of dignity for each human being if it wants
      to protect the same values it assigned to itself at the beginning of its history.
      This affirmation will be evident for many, dubious for others, and for many in
      the Anglo-Saxon world, unacceptable. The principle of autonomy is avoids some of
      the abuses that effected the birth of bioethics, but it is not enough to avoid
      them completely. Dignity or a similar concept is required.

PMID- 18611076
TI  - [Quality of life in the third age].
AB  - The aim of this article is to research the ethical problems concerning the
      quality of life that guarantees the elderly people's dignity. With this work, we
      attempt to the enrichment and value we give to a group that traditionally finds
      itself discredited in the contemporary age. The lack of productivity and the
      social burden that are attributed to this group take away whatever attractiveness
      they might have for other members of society. Therefore, we will analyse the
      properties of the quality of life and, than study the conditions of necessary for
      a dignified life of quality in the third age.

PMID- 18611077
TI  - [Environment and quality of life].
AB  - The aim of the article is to relate the concepts of quality of life and
      environment, through the analysis of the places where human activities take
      place, and how ecological, cultural and socioeconomic factors influence people's
      quality of life. Moreover, some proposals to improve the quality of life are
      made, either through the public (individual or collective) participation, or
      through the increasing consciousness about our own living habits.

PMID- 18611078
TI  - [Vaccines, biotechnology and their connection with induced abortion].
AB  - Diploid cells (WI-38, MRC-5) vaccines have their origin in induced abortions.
      Among these vaccines we fi nd the following: rubella, measles, mumps, rabies,
      polio, smallpox, hepatitis A, chickenpox, and herpes zoster. Nowadays, other
      abortion tainted vaccines cultivated on transformed cells (293, PER.C6) are in
      the pipeline: flu, Respiratory Syncytial and parainfluenza viruses, HIV, West
      Nile virus, Ebola, Marburg and Lassa, hepatitis B and C, foot and mouth disease,
      Japanese encephalitis, dengue, tuberculosis, anthrax, plague, tetanus and
      malaria. The same method is used for the production of monoclonal antibodies and
      other proteins, gene therapy and genomics. Technology enables us to develop the
      aforementioned products without resorting to induced abortion. Full disclosure of
      the cell origin in the labelling of vaccines and other products must be
      supported. There are vaccines from non-objectionable sources which should be made
      available to the public. When no alternative vaccines exist, ethical research
      must be promoted. Non-objectionable sources in the production of monoclonal
      antibodies, gene therapy and genomics must be encouraged. It is not be consistent
      to abstain from products originated in embryonic stem cells and at the same time
      approve of products obtained from induced abortions. It is of paramount
      importance to avoid that induced abortion technology seeps into every field of
      Medicine.

PMID- 18611079
TI  - Equity in health care.
AB  - It has long been known that a segment of the population enjoys distinctly better
      health status and higher quality of health care than others. To solve this
      problem, prioritization is unavoidable, and the question is how priorities should
      be set. Rational priority setting would seek equity amongst the whole population,
      the extent to which people receive equal care for equal needs. Equity in health
      care is an ethical imperative not only because of the intrinsic worth of good
      health, or the value that society places on good health, but because, without
      good health, people would be unable to enjoy life's other sources of happiness.
      This paper also argues the importance of the health care's efficiency, but at the
      same time, it highlights how any innovation and rationalization undertaken in the
      provision of the health system should be achieved from the consideration of human
      dignity, making the person prevail over economic criteria. Therefore, the
      underlying principles on which this health care equity paper is based are
      fundamental human rights. The main aim is to ensure the implementation of these
      essential rights by those carrying out public duties. Viewed from this angle,
      equity in health care means equality: equality in access to services and
      treatment, and equality in the quality of care provided. As a result, this paper
      attempts to address both human dignity and efficiency through the context of
      equity to reconcile them in the middle ground.

PMID- 18611080
TI  - Effects of diazinon on larvae of the Asian common toad (Bufo melanostictus,
      Schneider 1799).
AB  - Continuous subchronic exposure experiments were conducted to assess the effects
      of diazinon, an organophosphate pesticide, on the survival, growth and activity
      of larvae of the Asian common toad Bufo melanostictus. Two larval stages, the
      gill stage (Gosner stages 21 and 22) and gill-atrophy stage (Gosner stages 24 and
      25), were continuously exposed to 4 microg/L, 400 mirog/L, and 10 mg/L of
      commercial-grade diazinon for 30 d. Treatments and untreated controls were
      maintained in triplicate with water changed and pesticide concentrations renewed
      every 3 d. Observations showed that subchronic exposure to 400 microg/L and 10
      mg/L diazinon caused a significant dose-dependent increase in mortality compared
      to the control, regardless of the age at which larvae were exposed. One hundred
      percent mortality was observed in larvae exposed to 10 mg/L. No clear age-related
      sensitivity was evident in this study. The lethal concentrations at which 50% of
      the tadpoles (LC50) died during 30 d of continuous exposure were 6 and 7.5 mg/L
      for gill stage and gill-atrophy stage larvae, respectively. Diazinon impaired
      larval growth and activity. Tail abnormalities were apparent in larvae exposed to
      400 microg/L and 10 mg/L of diazinon. This investigation provides the first
      empirical evidence of the negative effects of diazinon on the survival, growth
      and activity of B. melanostictus. The high degree of diazinon toxicity in this
      study highlights the need to consider important nontarget groups when
      recommending safe levels of pesticide application.

PMID- 18611081
TI  - Potential effects of perfluorinated compounds in common cormorants from Lake
      Biwa, Japan: an implication from the hepatic gene expression profiles by
      microarray.
AB  - Contamination levels of perfluorinated compounds (PFCs), including
      perfluorooctanesulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorooctane
      sulfonamide (PFOSA), perfluorohexanesulfonate (PFHS), and perfluorooctanoic acid
      (PFOA), were determined in the livers of wild common cormorants (Phalacrocorax
      carbo) from Lake Biwa, Japan. Potential effects of PFCs alone and combined
      effects by complex mixture of PFCs and dioxins and related compounds (DRCs) were
      also assessed by gene expression profiling using a cormorant oligo array.
      Perfluorooctanesulfonate, PFNA, and PFOSA were detected in almost all liver
      samples analyzed, while concentrations of PFHS and PFOA were below the limit of
      quantification. The microarray data analyses revealed that hepatic PFC levels
      were correlated with the expression of 74 genes. Real-time reverse-transcript
      polymerase chain reaction data demonstrated that PFOS concentration was
      positively correlated with mRNA levels of glutathione peroxidase 1 and
      glutathione S-transferase alpha 3 and negatively correlated with levels of heat
      shock 70-kDa protein 8 and tumor rejection antigen 1 mRNAs. These results suggest
      the induction of antioxidant enzymes in response to oxidative stress caused by
      PFCs and the suppression of molecular chaperones, leading to reduction in protein
      stability. Moreover, multiple regression analyses identified seven significant
      models in which certain genes showed expression levels altered by accumulation of
      PFCs and DRCs. The regression models explained associations with cytochrome P450
      1A mRNA and protein expression levels, and its catalytic activity,
      ethoxyresorufin-O-deethylase of both PFNA and the 2,3,7,8-tetrachlorodibenzo-p
      dioxin toxic equivalent levels. Thus, the regression models suggested the
      potential of PFCs to enhance toxicities of DRCs. Since mixture toxicity is an
      urgent issue, further study is required to understand the effects of mixtures of
      PFCs and DRCs in wild cormorants.

PMID- 18611082
TI  - Vitellogenin as a biomarker for estrogenic effects in brown trout, Salmo trutta:
      laboratory and field investigations.
AB  - The sensitivity of juvenile brown trout towards estrogenic chemicals (17beta
      estradiol [E2], estrone [E1], 17alpha-ethinylestradiol [EE2], 4-tert-octylphenol
      [OP], and n-butylparaben [BP]) was tested in laboratory experiments with plasma
      and liver vitellogenin concentrations as endpoints. Vitellogenin concentrations
      were also assessed in juvenile brown trout collected in streams affected by
      agricultural runoff and discharges from scattered houses in the open land. In the
      laboratory, juvenile brown trout were exposed to the chemicals in flow-through
      tanks for 7 to 12 d and concentration-response relationships for the induction of
      vitellogenin synthesis were obtained. The actual exposure concentrations were
      determined by liquid chromatography-mass spectrometry. The median plasma
      vitellogenin concentration in first year control brown trout reared in
      recirculated groundwater was 165 ng/ml with 783 ng/ml as the highest value. The
      median effective concentration (EC50) values for vitellogenin induction (based on
      plasma concentrations) were 3.7 ng EE2/L, 15 ng E2/L, 88 ng E1/L, 68 microg BP/L,
      and 7 microg OP/L. Median effective concentrations derived from liver
      vitellogenin concentrations were similar. The 166 brown trout caught in the field
      were mainly first and second year fish and a few third year fish. Plasma
      vitellogenin concentrations were below 1000 ng/L in 146 of the fish, between 1000
      ng/L and 4234 ng/L in 19 fish and 5.3 x 10(6) ng/L in one male fish. Vitellogenin
      concentrations did not differ between first and second year fish, but were
      elevated in third year fish. The data may indicate that juvenile (<2 years) trout
      with plasma vitellogenin concentrations above 1000 ng/ml have had their
      vitellogenin synthesis induced by exposure to estrogens in the environment.
      Plasma and liver vitellogenin concentrations were closely correlated in brown
      trout with elevated vitellogenin concentrations. It is noteworthy, however, that
      exposure to synthetic estrogens (EE2, BP, and OP) resulted in higher liver
      concentrations (for the same plasma concentration) than exposure to the natural
      estrogens E1 and E2.

PMID- 18611083
TI  - Development and application of a species sensitivity distribution for temperature
      induced mortality in the aquatic environment.
AB  - Current European legislation has static water quality objectives for temperature
      effects, based on the most sensitive species. In the present study a species
      sensitivity distribution (SSD) for elevated temperatures is developed on the
      basis of temperature sensitivity data (mortality) of 50 aquatic species. The SSD
      applies to risk assessment of heat discharges that are localized in space or
      time. As collected median lethal temperatures (LT50 values) for different species
      depend on the acclimation temperature, the SSD is also a function of the
      acclimation temperature. Data from a thermal discharge in The Netherlands are
      used to show the applicability of the developed SSD in environmental risk
      assessment. Although restrictions exist in the application of the developed SSD,
      it is concluded that the SSD approach can be applied to assess the effects of
      elevated temperature. Application of the concept of SSD to temperature changes
      allows harmonization of environmental risk assessment for stressors in the
      aquatic environment. When a synchronization of the assessment methods is
      achieved, the steps to integration of risks from toxic and nontoxic stressors can
      be made.

PMID- 18611084
TI  - Effect of storage temperature on the activity of submitochondrial particles.
AB  - The submitochondrial particle (SMP) assay employs processed mammalian mitchondria
      to assess the toxicity of chemical contaminants in aqueous solutions. Particles
      and associated reagents are commercially available to support two individual
      procedures, the electron transfer (ETr) and reverse electron transfer (RET)
      assays. The objective of the present study was to assess the effect of storage
      temperature on SMP activity. One RET and one ETr assay were conducted with sodium
      dodecylsulfate on each of two vials of particles stored at -20 and -80 degrees C
      at periodic intervals over a six-month span. Results demonstrated that SMP could
      remain active in either assay through six months of storage at either
      temperature. However, there were isolated vials of particles stored at -20
      degrees C that exhibited unacceptable reductions in activity for both the ETr and
      the RET assays that were not related to storage duration. These results were used
      to develop guidance in assessing the acceptability of particle activity in SMP
      assays.

PMID- 18611085
TI  - Assessing the short-term and long-term burden of illness in cervical cancer.
AB  - Human papillomavirus (HPV) infection is associated with significant clinical,
      social, and financial burdens. Infection is often asymptomatic, which increases
      the risk of unwitting transmission. Up to 29 million American women between the
      ages of 14 and 59 years are currently infected, and 80% of women will contract
      the infection by 50 years of age. Persistent oncogenic HPV infection is the
      leading cause of cervical dysplasia and neoplasia, and evidence shows that
      oncogenic HPV is present in 99.7% of cervical cancer specimens. Cervical cancer
      and cervical dysplasias are responsible for the vast majority of morbidities and
      deaths associated with HPV-related illness. The direct annual healthcare costs
      for screening, treating, and managing abnormalities related to cervical cancer
      and cervical dysplasias in the United States are estimated to be as high as $4.6
      billion. Although the direct costs of cervical cancer are substantial, only 10%
      of all expenditures derive from invasive disease; more than two thirds of the
      total cost is attributable to screening and testing. Annual indirect costs
      resulting from lost productivity and loss of earnings due to premature death are
      also significant and are estimated to be higher than direct costs.

PMID- 18611086
TI  - Assessing secondary prevention methods for cervical cancer: costs and benefits in
      managed care.
AB  - Secondary prevention of cervical cancer through regular screening has been very
      successful since its widespread adoption in the 1940s. The death rate for
      cervical cancer declined 74% between 1955 and 1992, presumably owing to the
      introduction of the Papanicolaou's cervical smear (Pap test) and greater use of
      organized screening. Until now, this is the closest we have come to scoring a win
      in the ongoing fight against cervical cancer. Although secondary measures for
      preventing cervical cancer remain a mainstay in managed care, screening
      methodologies and processes have several inherent weaknesses, largely because
      successful screening depends on patient cooperation and adherence. Screening
      rates have improved, but approximately 20% of the target population in commercial
      plans remains unscreened. Weaknesses related to the specificity and sensitivity
      of cervical screening methodologies compound the problem of preventing cervical
      cancer through screening. Secondary prevention methods constitute the greatest
      proportion of direct costs in cervical disease, by far. Should a patient receive
      an abnormal test result, costs accelerate significantly. Methods used to resolve
      test abnormalities, such as repeat screening, colposcopy/biopsy, and human
      papillomavirus deoxyribonucleic acid testing, add to the overall financial burden
      of secondary prevention in these cases.

PMID- 18611087
TI  - Ethnic disparities in cervical cancer illness burden and subsequent care: a
      prospective view in managed care.
AB  - Costs associated with cervical neoplasia and cancer impose a significant burden
      on managed care. More than 50,000 cases are diagnosed annually in the United
      States, accumulating approximately $4.6 billion in costs per year. The apparent
      disparity of care related to screening and treatment among specific ethnic groups
      and economically disadvantaged subpopulations results in elevated cervical cancer
      mortality rates and adds to managed care's burden. This is likely the result of
      several factors, including differences in the stage of cervical cancer at
      diagnosis, cultural barriers to undergoing regular cervical screening, and
      impaired access to follow-up care after receiving abnormal Papanicolaou smear
      test results. To overcome socioeconomic and cultural barriers to providing
      adequate care for patients with cervical cancer, the implementation and
      effectiveness of secondary prevention methods should be revisited and options for
      primary prevention, such as human papillomavirus vaccination, should be explored.
      Vaccines have the potential to reduce disparities in care, particularly if they
      are provided to economically disadvantaged women or those whose culture serves as
      an obstacle to obtaining appropriate care. If action is not taken to broaden
      access to vaccines, it is likely that managed care will continue to bear the
      burden of increased costs due to poor outcomes.

PMID- 18611088
TI  - 5-Alpha reductase inhibitors in men with an enlarged prostate: an evaluation of
      outcomes and therapeutic alternatives.
AB  - This article presents background information and highlights key findings from a
      managed care perspective related to enlarged prostate (EP) in Medicare-eligible
      patients. This article does not provide a comprehensive review of EP but instead
      attempts to increase the current understanding of EP through discussion of its
      prevalence in men aged > or =65 years, its associated economic burden, and some
      available treatment options. This supplement includes 3 additional articles, all
      of which present data from a naturalistic, managed care setting. The article by
      Fenter et al assesses differences in outcomes between elderly EP patients treated
      with finasteride and those treated with dutasteride in relation to the risks of
      acute urinary retention and prostate-related surgery. Issa et al conduct a
      comparative analysis of the combined use of alpha-blockers and 5-alpha reductase
      inhibitors to treat EP. The final article compares medical costs incurred within
      the first year of initiating treatment for EP patients receiving finasteride
      versus dutasteride. This supplement is intended to assist managed care formulary
      decision makers in evaluating key clinical and economic data that differentiate
      dutasteride and finasteride within the Medicare-aged population. Although the
      information presented is not designed to illustrate the superiority of one
      product over the other, it answers important questions in relation to treating EP
      in elderly men and raises substantial issues beyond medication costs.

PMID- 18611089
TI  - Dutasteride vs finasteride: assessment of differences in acute urinary retention
      rates and surgical risk outcomes in an elderly population aged > or =65 years.
AB  - OBJECTIVE: To determine comparative differences on rates of acute urinary
      retention (AUR) and prostate-related surgeries among patients aged > or =65 years
      treated with dutasteride or finasteride. METHODS: For this retrospective
      analysis, medical/pharmacy claims data from July 1, 2003, to June 30, 2006, were
      analyzed for enlarged prostate patients aged > or =65 years treated with 5-alpha
      reductase inhibitors (5ARIs) regardless of alpha-blocker use. Charlson
      Comorbidity Index, Thomson Medstat Disease Staging, and propensity score matching
      techniques were used for comparative analysis. RESULTS: A total of 5090 patients
      met selection criteria. After 1 year of 5ARI therapy, the AUR rate was lower for
      dutasteride (12%) when compared with finasteride (14.7%) (odds ratio [OR], 0.79;
      P = .0042). Risks for prostate-related surgeries were also lower among
      dutasteride-treated patients (3.9% vs 5.1%, respectively; OR, 0.77; P = .03).
      CONCLUSION: Important therapeutic outcome differences exist between dutasteride
      and finasteride. Patients treated with dutasteride were significantly less likely
      to experience AUR and prostate-related surgeries than finasteride patients.

PMID- 18611090
TI  - Comparative analysis of alpha-blocker utilization in combination with 5-alpha
      reductase inhibitors for enlarged prostate in a managed care setting among
      Medicare-aged men.
AB  - OBJECTIVE: To evaluate the likelihood of alpha-adrenergic antagonist (alpha
      blocker) discontinuation in combination with dutasteride or finasteride among
      patients aged > or =65 years with enlarged prostate. METHOD: This retrospective
      analysis used 2003-2006 data representing more than 30 million managed care
      members. Medical/pharmacy claims were used to select patients, matched 1:1 using
      propensity scoring. The proportion remaining on alpha-blocker therapy more than
      12 months and time to discontinuation were compared between groups, controlling
      for covariates using survival analysis. RESULTS: The matched sample included 1674
      patients. Alpha-blocker therapy discontinuation was observed at 90 days (86.9%
      dutasteride patients and 91.8% finasteride patients remained on alpha-blocker
      therapy). After 12 months, more dutasteride patients discontinued (38.1%
      remained) alpha-blocker therapy than finasteride patients (56.3% remained).
      CONCLUSIONS: Patients discontinued alpha-blocker therapy as early as 3 months.
      Those taking dutasteride were 64% more likely to discontinue alpha-blocker
      therapy than patients taking finasteride. Dutasteride's impact on discontinuation
      may have important implications and should be examined further.

PMID- 18611091
TI  - Cost comparison of finasteride and dutasteride for enlarged prostate in a managed
      care setting among Medicare-aged men.
AB  - OBJECTIVE: To assess cost differences between dutasteride and finasteride use
      within the first year of initiating treatment for enlarged prostate (EP) among
      men aged > or =65 years in a managed care setting. METHODS: For this
      retrospective analysis, medical/pharmacy claims data from July 1, 2003, to June
      30, 2006, were analyzed for EP patients aged > or =65 years who were treated with
      dutasteride or finasteride. Analysis of average monthly costs over each patient's
      1-year follow-up period incorporated total charges for EP-related medical care,
      including physician, inpatient and outpatient hospital care, emergency
      department, and other ancillary services. RESULTS: A total of 4498 patients met
      selection criteria, with comparable demographics between treatment cohorts.
      Patients taking dutasteride incurred $51 less per month in medical expenses than
      finasteride-treated patients ($122 vs $173; P <.001), attributable to lower
      monthly inpatient hospitalization costs ($55.84 vs $70.34), outpatient costs
      ($22.07 vs $44.25), and physician office visit costs ($40.69 vs $51.10).
      CONCLUSION: Medicare-aged patients treated with dutasteride incurred $51 less per
      month in medical costs than those treated with generic finasteride, suggesting
      that the higher price of dutasteride may be offset by decreased medical resource
      consumption.

PMID- 18611092
TI  - What does the RAND Health Insurance Experiment tell us about the impact of
      patient cost sharing on health outcomes?

PMID- 18611093
TI  - Language disparities and timely care for children in managed care Medicaid.
AB  - OBJECTIVE: To examine the relationship of race/ethnicity, language, communication
      with providers, and interpreter use with timeliness of illness and routine care
      for children in managed care Medicaid. STUDY DESIGN: Cross-sectional study using
      data from the Consumer Assessment of Health Plans Survey, which was administered
      to parents of children less than 15 years of age in Washington State managed care
      Medicaid in 2000. METHODS: Predictors of interest were child's race/ethnicity,
      parent's primary language at home, difficulty communicating with the child's
      providers because of language, and need and use of interpreters. The primary
      outcomes were how often (always, usually, sometimes, or never) the child received
      illness and routine care as soon as wanted. Analyses used multivariate ordered
      logistic regression and model-based direct adjustment. RESULTS: A total of 5142
      children were included. In adjusted analyses, children received illness and
      routine care significantly less often than wanted if the parent's primary
      language at home was not English; the parent ever had difficulty communicating
      with the provider; and the parent needed but did not always get an interpreter.
      CONCLUSION: Language barriers were associated with decreased timeliness of care
      for children in managed care Medicaid.

PMID- 18611094
TI  - Automated patient assessments after outpatient surgery using an interactive voice
      response system.
AB  - OBJECTIVE: To test the feasibility and utility of an interactive voice response
      system (IVRS) for monitoring patients after outpatient surgery. METHODS: We
      studied consecutive patients undergoing gynecologic day surgery. The IVRS called
      patients on the first postoperative day and asked them if they were experiencing
      new problems. Feasibility was assessed in terms of call responses and acceptance
      by patients. Utility was measured in terms of the ability of the IVRS to identify
      adverse events (AEs), defined as procedure-related symptoms requiring a physician
      or hospital visit. We contacted patients 30 days later to elicit their
      perceptions of the IVRS and determine AE status. RESULTS: Follow-up was complete
      for 249 of 270 enrolled patients (92%). The IVRS successfully contacted 130
      patients (52%). Of the 22 patients (17%) who required a follow-up phone call, 9
      had a new problem related to surgery, 7 had new or worsening symptoms, 6 wanted
      to speak with a nurse, and 1 had a medication-related problem. Patients
      remembering the automated call (n = 96) reported the system easy to use (82%) and
      comprehend (86%). Most patients (68%) preferred the IVRS to a personal follow-up
      call (probability greater than 50%, P <.001). AEs occurred in 40 patients (16%;
      95% confidence interval = 12%, 21%). The IVRS did not identify any AEs because
      90% of these occurred after the automated call. CONCLUSION: An IVRS-based method
      of monitoring outpatient surgery patients is feasible. To improve utility, calls
      must occur later than first postoperative day.

PMID- 18611095
TI  - Economic assessment of initial maintenance therapy for chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To compare the effects of initial maintenance therapy with fluticasone
      250 microgram plus salmeterol 50 microgram in a single inhaler versus other
      inhaled medications on exacerbation risks and treatment costs among chronic
      obstructive pulmonary disease (COPD) patients. STUDY DESIGN: A retrospective
      observational analysis was conducted by using medical/pharmacy claims from a
      large managed care database between January 2000 and February 2004. Patients age
      40 years or older with a primary diagnosis of COPD (International Classification
      of Diseases, Ninth Revision, Clinical Modification code 490, 491, 492, or 496),
      at least 18 months of continuous eligibility, and an index prescription for
      fluticasone/salmeterol combination, salmeterol alone, inhaled corticosteroid
      alone, ipratropium/albuterol combination, or ipratropium alone (reference) were
      identified. METHODS: Time to first COPD-related hospitalization or emergency
      department (ED) visit was estimated by using Cox proportional hazard models. All
      cause and COPD-related treatment costs were estimated by using generalized linear
      models with a gamma distribution and log link. Multivariable regressions were
      used, controlling for age, sex, comorbidities, COPD subtype, preindex
      medications, and hospitalizations and ED visits. RESULTS: Initial maintenance
      therapy with fluticasone/salmeterol combination was associated with a 31% to 56%
      lower risk of hospitalization or ED visit compared with ipratropium alone,
      adjusting for baseline characteristics and preindex resource utilization.
      Fluticasone/salmeterol combination therapy was related to lower medical costs,
      higher pharmacy costs, and almost similar total costs in all populations studied.
      CONCLUSION: Fluticasone/salmeterol combination therapy was considered to be cost
      effective compared with ipratropium alone because it achieved better clinical
      outcomes with similar or lower treatment costs.

PMID- 18611096
TI  - Identifying high-risk asthma with utilization data: a revised HEDIS definition.
AB  - OBJECTIVE: To develop a definition of high-risk asthma that more precisely
      identifies patients needing case management than the 2006 Healthcare
      Effectiveness Data and Information Set (HEDIS) definition. STUDY DESIGN: Two-year
      claims-based study, with cross-sectional phone survey data, for a sample of 769
      youths (age 11-17 years) with asthma. METHODS: The 2006 HEDIS measure defines
      high-risk asthma as meeting any of the following criteria: >1 emergency
      department (ED) visits, > or =1 hospitalizations for asthma, > or =4 asthma
      medication prescriptions, or > or =4 ambulatory visits for asthma with > or =2
      prescriptions for asthma medication in 1 year. We created a revised definition (>
      or =1 ED visits or > or =1 hospitalizations for asthma or > or =1 oral steroid
      prescriptions for asthma) and identified patients with high-risk asthma in year 1
      according to each definition. We compared the 2 groups on demographic and
      clinical characteristics, and healthcare utilization and costs in years 1 and 2.
      RESULTS: The revised definition identified 29% of the sample as having high-risk
      asthma, whereas the 2006 definition identified 67%. Compared with the 2006
      definition, the revised definition identified patients with significantly greater
      asthma-related physical health problems and higher medical costs in year 1. In
      year 2, youths classified as high risk by the revised definition made more ED
      visits and were more likely to use oral steroids than those classified as high
      risk by the 2006 definition. CONCLUSION: The revised high-risk asthma definition
      identifies half as many individuals and is better able to identify patients with
      poorly controlled asthma in the subsequent year.

PMID- 18611098
TI  - Self-monitoring of blood glucose levels in patients with type 2 diabetes mellitus
      not taking insulin: a meta-analysis.
AB  - OBJECTIVE: To perform a meta-analysis of randomized controlled trials (RCTs) and
      systematic reviews evaluating the efficacy of self-monitoring of blood glucose
      (SMBG) levels among patients with diabetes mellitus (DM). STUDY DESIGN: Meta
      analysis of RCTs among patients with DM not taking insulin comparing patients
      with SMBG versus those without SMBG and reporting results as change in
      glycosylated hemoglobin (A1C) values. METHODS: Prior systematic reviews and a
      PubMed search were used to identify studies. Data were extracted by trained
      physician reviewers working in duplicate. Trials were classified according to
      duration of the intervention, and random-effects meta-analysis was used to pool
      results. RESULTS: Three trials of SMBG of 3 months' duration were too
      heterogeneous to pool. Nine other trials were identified. Five trials of SMBG of
      6 months' duration yielded a pooled effect estimate of a decrease in mean A1C
      values of -0.21% (95% confidence interval [CI], -0.38% to -0.04%). Four trials
      that reported outcomes of 1 year or longer yielded a pooled effect estimate of a
      decrease in mean A1C values of -0.16% (95% CI, -0.38% to 0.05%). Three trials
      reported hypoglycemic outcomes, which were increased in the patients using SMBG,
      although this mostly involved asymptomatic or mild episodes. CONCLUSIONS: At
      most, SMBG produces a statistically significant but clinically modest effect in
      controlling blood glucose levels in patients with DM not taking insulin. It is of
      questionable value in helping meet target values of glucose control.

PMID- 18611097
TI  - Financial incentives for quality in breast cancer care.
AB  - OBJECTIVES: To examine the use of financial incentives related to performance on
      quality measures reported by oncologists and surgeons associated with a
      population-based cohort of patients with breast cancer in Los Angeles County,
      California, and to explore the physician and practice characteristics associated
      with the use of these incentives among breast cancer care providers. STUDY
      DESIGN: Cross-sectional observational study. METHODS: Physician self-reported
      financial arrangements from a survey of 348 medical oncologists, radiation
      oncologists, and surgeons caring for patients with breast cancer in Los Angeles
      County (response rate, 76%). Physicians were asked whether they were subject to
      financial incentives for quality (ie, patient satisfaction surveys and adherence
      to practice guidelines). We examined the prevalence and correlates of incentives
      and performed multivariate logistic regression analyses to assess predictors of
      incentives, controlling for other covariates. RESULTS: Twenty percent of
      respondents reported incentives based on patient satisfaction, and 15% reported
      incentives based on guideline adherence. The use of incentives for quality in
      this cohort of oncologists and surgeons was modest and was primarily associated
      with staff- or group-model health maintenance organization (HMO) settings. In
      other settings, important predictors were partial physician ownership interest,
      large practice size, and capitation. CONCLUSIONS: Most cancer care providers in
      Los Angeles County outside of staff- or group-model HMOs are not subject to
      explicit financial incentives based on quality-of-care measures. Those who are,
      seem more likely to be associated with large practice settings. New approaches
      are needed to direct financial incentives for quality toward specialists outside
      of staff- or group-model HMOs if pay-for-performance programs are to succeed in
      influencing care.

PMID- 18611099
TI  - Breakthrough pain in the management of chronic persistent pain syndromes.
AB  - Chronic pain results from tissue damage (nociceptive) or damage to the nerves or
      nervous system (neuropathic); it can stem from internal organs or cavity linings
      (visceral) or from the body's tissues (somatic). Mixed pain results from any
      number or combination of these types. Breakthrough pain (BTP) is a transitory,
      and often excruciating, flare that occurs against a background of chronic pain
      otherwise controlled by opioids. BTP is highly prevalent in patients with chronic
      pain of both cancer and noncancer origin, with episodes typically occurring
      several times daily that tend to peak within 10 to 30 minutes. Patients with BTP
      also endure heightened chronic pain, worsened physical function, and
      psychological distress. Several subtypes of BTP have been identified, including
      idiopathic, incident, and end-of-dose failure. The BTP Questionnaire is available
      to identify and characterize BTP and help determine the best treatment strategy
      for individual patients. This article reviews the etiology, prevalence, and
      characteristics of BTP along with assessment of patients and therapeutic
      strategies available to treat this condition.

PMID- 18611100
TI  - Pharmacotherapeutic management of breakthrough pain in patients with chronic
      persistent pain.
AB  - Breakthrough pain (BTP) is experienced by many patients being treated with
      opioids for the management of chronic persistent pain. Control of BTP has been
      problematic since, until recently, the pharmacokinetics of older treatments was
      largely incompatible with the onset and duration of these pain episodes. Newer
      agents are now available that better approximate the timing of BTP episodes, and
      their use is increasingly being integrated into opioid-based pain management
      strategies. Successful management of BTP can improve treatment satisfaction and
      the quality of life of patients with chronic persistent pain of both cancer and
      noncancer origins. This article reviews the types of BTP, the therapeutic options
      available to manage BTP, and the tools designed to detect and minimize the risk
      of aberrant drug-related behaviors potentially associated with opioid
      medications.

PMID- 18611101
TI  - A health economic model of breakthrough pain.
AB  - Although the literature adequately addresses the biologic basis, epidemiology,
      and management of breakthrough pain (BTP), it does not yet describe the full
      impact of this troubling, widespread phenomenon. The risks of a scanty
      understanding of BTP impact are failure to take preventive measures,
      underdiagnosis, undertreatment, and inappropriate management. Studies to date of
      the impact of BTP have followed pharmacoeconomic approaches. Building on prior
      efforts, this paper develops a more comprehensive health economic model that
      encompasses the full spectrum of costs, outcomes, risks and benefits associated
      with BTP and its management. The authors provide a rubric within which
      stakeholders--including providers, institutional leaders, administrators, and
      policymakers--can systematically balance the myriad potential effects of
      different treatment scenarios to guide decision-making. The paper then extends
      this model to the population level, providing a template for health economic
      analysis of alternate strategies for managing BTP, and delineating steps for
      accomplishing the analysis.

PMID- 18611102
TI  - Stroke and TIA: epidemiology, risk factors, and the need for early intervention.
AB  - The risk of recurrent stroke in patients who have suffered a prior stroke or
      transient ischemic attack (TIA) is significant. It is imperative that individuals
      who report symptoms of a cerebrovascular event receive immediate medical
      attention--preferably at a hospital--to help determine its origin and impact.
      Many researchers recommend that any evaluation include neuroimaging studies to
      target those patients who would benefit most from secondary prevention, such as
      antithrombotic therapy. This article defines the 2 main types of stroke and their
      respective subtypes and discusses the debate over how to define stroke versus
      TIA. Additionally, the article talks about the incidence of stroke, related
      morbidity and mortality rates, and several risk factors that predispose an
      individual to stroke and recurrent stroke. Several systems have been established
      to help determine the likelihood of stroke for patients with concurrent risk
      factors. Measures for secondary prevention can be initiated to address many of
      these risk factors. The importance of early intervention cannot be
      underestimated. Rapid treatment following a stroke or TIA can minimize
      cerebrovascular damage and prevent recurrence; addressing modifiable risk factors
      can reduce the risk of subsequent cardiovascular and cerebrovascular events.
      Facilitating the initiation of effective secondary preventive therapy must become
      a priority in managed care.

PMID- 18611103
TI  - Therapeutic interventions for prevention of recurrent ischemic stroke.
AB  - Patients who suffer ischemic stroke or transient ischemic attack (TIA) are at
      increased risk for subsequent cerebrovascular events. Secondary prevention is
      essential to reduce risks of recurrence and should include lifestyle modification
      to improve cardiovascular health, along with strict control of blood pressure,
      glucose, and lipids. Recurrent stroke in ischemic stroke patients is likely to be
      the same subtype as the initial stroke, and treatment should be unique to the
      stroke subtype and patient risk factors. This article presents an overview of the
      recommendations for the secondary prevention of ischemic stroke or TIA and a
      review of the evidence supporting the role of antiplatelet therapy in managing
      the risk of recurrent noncardioembolic stroke. Although anticoagulants are
      recommended preventive treatment for cardioembolic stroke, they can increase the
      patient's risk of bleeding complications and are not recommended for all subtypes
      of ischemic stroke. The American Heart Association/American Stroke Association
      guidelines recommend 3 antiplatelet regimens for the secondary prevention of
      noncardioembolic ischemic stroke: aspirin (ASA), clopidogrel, and combined ASA +
      extended-release (ER) dipyridamole (DP). ASA + ER-DP is recommended over ASA
      alone. Several studies have established the effectiveness of these 3 antiplatelet
      regimens as first-line options in the secondary prevention of noncardioembolic
      ischemic stroke. Clopidogrel monotherapy is a reasonable alternative for patients
      who cannot tolerate ASA. ASA + ER-DP has been shown to be more effective than ASA
      alone and does not increase the risk of bleeding. Effective secondary prevention
      must also address modifiable risk factors, such as obesity, smoking, and
      excessive alcohol consumption.

PMID- 18611104
TI  - Managed care considerations.
AB  - Stroke is the third leading cause of death in the United States and among the
      most costly diseases. Most strokes are categorized as ischemic, and 10% to 15%
      are preceded by a transient ischemic attack (TIA). Stroke survivors suffer levels
      of disability and handicap that range from mild to very severe, and they rarely
      make a complete recovery. Initial stroke patients are at considerable risk for
      recurrent stroke, which can compound a patient's impairment and associated costs.
      This article discusses the burden of stroke on patients and caregivers, the risk
      of stroke recurrence, and the pharmacoeconomics of antiplatelet therapy. Studies
      show that effective secondary prevention such as antiplatelet therapy can improve
      clinical outcomes in patients who have experienced TIA or prior stroke. Recently
      updated guidelines for secondary stroke prevention from the American Heart
      Association/American Stroke Association recommend administering antiplatelet
      agents rather than anticoagulants for patients who experienced an ischemic
      noncardioembolic stroke or TIA to reduce the risk of stroke or other
      cardiovascular events. The guidelines state that aspirin (ASA), ASA + extended
      release dipyridamole (DP), and clopidogrel are acceptable initial treatment
      options for these patients. A recent pharmacoeconomic analysis of all 3 therapies
      concluded that ASA and ASA + DP offer cost-effective secondary prevention for
      patients who have suffered a mild initial stroke. Understanding the role of
      antiplatelet therapy in secondary prevention can help the managed care community
      optimize clinical and economic outcomes, thereby reducing the overall burden of
      cerebrovascular disease.

PMID- 18611106
TI  - A practical approach to instrument selection, evaluation, basic financial
      management and implementation in pathology and research.
AB  - In response to increasingly complex demands in terms of productivity and budgets,
      there is a critical need to avoid mistakes during instrument selection that will
      be financially costly, and adversely affect customers, staff, productivity and
      test turnaround time. As there is no "one size fits all", guidelines must be
      appropriate to permit informed decision making. A Medline search was conducted to
      assess background knowledge in this area, using the terms "laboratory instrument
      selection" and "laboratory instrument evaluation". Searches returned over 800
      articles, of which only seven were directly related to the topic of the search,
      with most outdated, and suggesting a paucity of appropriate information.
      Additional resources used included the American Association of Clinical Chemistry
      (AACC) website and the Internet. Appropriate criteria for instrument selection
      were established in the current report based on subjective and objective
      (technical) evaluations. Additionally, a sound and simple financial approach is
      also suggested to help in making informed decisions and avoid costly mistakes. We
      propose that such a process as outlined in our report will protect laboratories
      from making costly and avoidable mistakes in the acquisition of major equipment.

PMID- 18611105
TI  - Comprehensive profiling of the human circulating endocannabinoid metabolome:
      clinical sampling and sample storage parameters.
AB  - BACKGROUND: Endogenous cannabinoid-receptor ligands (endocannabinoids) and over a
      dozen related metabolites now comprise the "endocannabinoid metabolome". The
      diverse (patho)physiological roles of endocannabinoids, the predictive/diagnostic
      utility of systemic endocannabinoid levels, and the growing interest in
      endocannabinoid-related pharmacotherapeutics mandate a valid clinical protocol
      for processing human blood that does not jeopardize profiling of the circulating
      endocannabinoid metabolome. METHODS: We systematically evaluated the potential
      effect of pre-analytical variables associated with phlebotomy and sample
      handling/work-up on the human-blood endocannabinoid metabolome as quantified by
      state-of-the-art liquid chromatography-mass spectrometry. RESULTS: Neither
      subject posture during phlebotomy nor moderate activity beforehand influenced the
      blood levels of the 15 endocannabinoid-system lipids quantified. Storage of fresh
      blood at 4 degrees C selectively enhanced ethanolamide concentrations
      artifactually without affecting monoglycerides and nonesterified fatty acids,
      such as arachidonic acid. In marked contrast, ethanolamides and monoglycerides
      remained stable through three plasma freeze/thaw cycles, whereas plasma
      arachidonic acid content increased, probably a reflection of ongoing metabolism.
      CONCLUSIONS: Class- and compound-selective pre-analytical influences on
      circulating human endocannabinoid levels necessitate immediate plasma preparation
      from fresh blood and prompt plasma apportioning and snap-freezing. Repeated
      plasma thawing and refreezing should be avoided. This protocol ensures sample
      integrity for evaluating the circulating endocannabinoid metabolome in the
      clinical setting.

PMID- 18611107
TI  - Measurement of mycophenolic acid in plasma or serum by a commercial enzyme
      inhibition technique in comparison with a high performance liquid chromatography
      method.
AB  - BACKGROUND: Mycophenolic acid (MPA) is the primary active metabolite of the
      immunosuppressant mycophenolate mofetil. High performance liquid chromatography
      (HPLC) is commonly used for therapeutic drug monitoring (TDM) of MPA but requires
      batched runs. Recently, an enzyme inhibition assay (EIA) was approved for MPA TDM
      on random-access platforms using either serum or EDTA plasma. We evaluated the
      EIA on a Roche Integra 400 using serum and heparinized plasma in comparison with
      a validated HPLC method. METHODS: Heparinized plasma from leftover clinical
      samples on which MPA was ordered along with paired serum samples, drawn at the
      same time for other clinical tests, were used for the method comparison. RESULTS:
      The EIA was linear from 3.1 to 44.0 micromol/L with an accuracy of 93.9%-107.1%.
      The intra- and inter-day variations were 0.5%-2.7% and 1.6%-2.1%, respectively.
      The limit of detection was 0.8 micromol/L and the limit of quantification was 3.1
      micromol/L. The method showed a mean bias of 0.6 micromol/L (7.6%) in serum
      samples (3.1-34.1 micromol/L) vs. the HPLC method using paired plasma (n=229).
      Heparinized plasma (n=114) vs. serum showed a mean bias of -0.1 mumol/L (-1.6%)
      by the EIA. CONCLUSIONS: The random-access EIA on Integra 400 is acceptable for
      clinical MPA TDM in either serum or heparinized plasma.

PMID- 18611110
TI  - Metabolomic strategies to identify tissue-specific effects of cardiovascular
      drugs.
AB  - BACKGROUND: The number of patients eligible for cardiovascular therapies in
      general is forecast to increase substantially in the coming decades. However, the
      current list of potential future cardiovascular blockbuster drugs is alarmingly
      short. There is thus a clear need for innovative strategies to increase the
      efficiency of drug development pipelines by establishing new sensitive biomarkers
      to monitor drug efficacy and safety in the context of complexity of lipoprotein
      metabolism targeted by the cardiovascular drugs. METHODS: Metabolomics is a
      discipline dedicated to the systematic study of small molecules in cells, tissues
      and biofluids. Since lipids (including cholesterol), as well as other
      metabolites, are key constituents of lipoprotein particles and are thus part of
      the complex lipoprotein metabolism that includes exchange of lipids and
      metabolites with peripheral tissues, cardiovascular drug safety and efficacy
      needs to be addressed in the context of systemic lipid metabolism.
      RESULTS/CONCLUSION: Metabolomics, lipidomics in particular, is expected to make
      an important impact on the discovery and development of cardiovascular therapies.

PMID- 18611111
TI  - Echocardiography, a non-invasive method for the assessment of cardiac function
      and morphology in preclinical drug toxicology and safety pharmacology.
AB  - BACKGROUND: Echocardiography (EC) is a method used for the investigation of
      cardiac morphology and function. Two-dimensional EC gives a visualisation of the
      morphology of the heart. M-mode EC allows heart function to be monitored. Pulsed
      Doppler EC is the method of choice to measure blood flows. OBJECTIVE: To describe
      the information EC can provide for cardiovascular investigation in laboratory
      animals, with a special focus on the potential helpfulness of EC in preclinical
      toxicology and safety pharmacology. METHODS: This review includes publications
      describing the methodology of EC and its application to several animal species
      used in biological experimentation. RESULTS/CONCLUSION: EC has been established
      in dogs, monkeys, rodents, rabbits and pigs. As demonstrated by experiments in
      different species, EC can be particularly helpful in toxicology and safety
      pharmacology, based on the amount of information it can give on the causes and
      consequences of drug adverse effects on the cardiovascular system. Furthermore,
      EC does not require any surgery and is therefore a key refinement compared to
      invasive methods generally used for investigating the cardiovascular function in
      laboratory animals. Despite some limitations of the method (the need for trained
      people, time required for an accurate EC recording, lack of current validation),
      EC should be further developed in preclinical toxicology and safety pharmacology.

PMID- 18611113
TI  - Utilization of membrane vesicle preparations to study drug-ABC transporter
      interactions.
AB  - BACKGROUND: The last 15 years have marked an expansion in our understanding of
      how ABC transporters modulate the pharmacokinetic properties of drugs. Assays
      based on different membrane preparations were one of the first methods developed
      to study ABC transporters. Later, they turned out to be valuable tools to gain
      insight into the nature of drug-ABC transporter interactions. OBJECTIVES:
      Membranes prepared from different sources have been used and characterized; based
      on the biochemical characteristics of the transport process, a number of
      different assay types have been developed. METHODS: This review focuses on the
      current experiences on how different membrane-based assays can be utilized in
      pharmaceutical R&D. Sources of membrane preparations, available assay types and
      correlation studies between different in-vitro and in-vivo methods are discussed.
      RESULTS/CONCLUSION: Membrane-based assays are valuable tools in drug discovery to
      characterize drug-ABC transporter interactions.

PMID- 18611114
TI  - High-throughput enzymology and combinatorial mutagenesis for mining cytochrome
      P450 functions.
AB  - BACKGROUND: High-throughput (HT) characterization of drugs for potential
      biotransformation and interaction is routine in pharmaceutical industry.
      OBJECTIVE: HT approaches were extended to enzyme studies for identifying
      combinations of structural elements that control substrate specificity. METHODS:
      Structure-based and combinatorial mutagenesis have been applied with success to
      decipher P450 structure-function relationships. The idea is to measure activities
      on a library of combinatorial variants of similar structure with a large
      collection of substrates presenting a similar chemical scaffold. This
      combinatorial approach is then associated to multivariate statistics to relate
      functional features to structural determinants. RESULTS/CONCLUSION: A method to
      measure HT kinetics is presented. The proposed statistical approach is
      illustrated with tri- and tetracyclic substrates and artificial variant enzymes
      of the CYP1A subfamily.

PMID- 18611115
TI  - Replacement therapy of oral hydrocortisone in adrenal insufficiency: the
      influence of gastrointestinal factors.
AB  - BACKGROUND: Replacing glucocorticoids in primary adrenal insufficiency (AI) or
      Addison's disease (AD) is today based on oral replacement therapy with
      hydrocortisone in a conventional immediate-release tablet. It is recognised that
      physiological gastrointestinal factors may have a strong influence on the plasma
      concentration-time profile of hydrocortisone. Hydrocortisone has a sufficiently
      high permeability in both the small and large intestine, but in vivo dissolution
      from the available oral product is limited at higher doses. The short elimination
      half-life of hydrocortisone (approximately 1.5 h) when given in traditional
      immediate-release dosage forms requires two or more dose administrations per day,
      with high peaks and low trough values in between. The endogenous secretion of
      cortisol from the adrenal cortex follows a distinct diurnal pattern, with
      increasing and high plasma levels of cortisol early in the morning (approximately
      05.00-08.00 h), intermediate levels in the afternoon, low levels in the evening
      and a cortisol-free interval at night. There is, therefore, a clinical need for
      an improved drug delivery product that more closely follows the circadian pattern
      of cortisol in plasma. OBJECTIVE: The pharmaceutical and biopharmaceutical
      properties of the dosage form containing hydrocortisone will determine intestinal
      absorption rate and the plasma concentration-time profile of hydrocortisone
      (cortisol). Factors that cause or result in pharmacokinetic variability should be
      understood and avoided where possible. METHODS: A literature search was performed
      with the aim of covering the field of gastrointestinal drug absorption of
      hydrocortisone in AD. RESULTS/CONCLUSION: Novel oral drug delivery principles for
      facilitation of once-daily dosing and providing a safe and physiologically based
      plasma concentration-time profile of hydrocortisone in replacement therapy are
      discussed. Development of new drug formulations is ongoing and will certainly
      lead to an improved replacement therapy of AD with hydrocortisone. Of special
      interest is a therapy based on once-daily treatment and less fluctuating plasma
      concentrations of hydrocortisone (cortisol).

PMID- 18611116
TI  - Structure-ADME relationship: still a long way to go?
AB  - BACKGROUND: Theoretical models for predicting absorption, distribution,
      metabolism and excretion (ADME) properties play increasingly important roles in
      support of the drug development process. OBJECTIVE: We briefly review the in
      silico prediction models for three important ADME properties, namely, aqueous
      solubility, human intestinal absorption, and oral bioavailability. METHODS:
      Rather than giving detailed descriptions of the ADME prediction models, we focus
      on the discussions of the prediction accuracies of the in silico models.
      RESULTS/CONCLUSION: We find that the robustness and predictive capability of the
      ADME models are directly associated with the complexity of the ADME property. For
      the ADME properties involving complex phenomena, such as bioavailability, the in
      silico models usually cannot give satisfactory predictions. Moreover, the lack of
      large and high-quality data sets also greatly hinder the reliability of ADME
      predictions. While considerable progress has been achieved in ADME predictions,
      many challenges remain to be overcome.

PMID- 18611112
TI  - Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily.
AB  - BACKGROUND: Aldehydes are highly reactive molecules. While several non-P450
      enzyme systems participate in their metabolism, one of the most important is the
      aldehyde dehydrogenase (ALDH) superfamily, composed of NAD(P)+-dependent enzymes
      that catalyze aldehyde oxidation. OBJECTIVE: This article presents a review of
      what is currently known about each member of the human ALDH superfamily including
      the pathophysiological significance of these enzymes. METHODS: Relevant
      literature involving all members of the human ALDH family was extensively
      reviewed, with the primary focus on recent and novel findings. CONCLUSION: To
      date, 19 ALDH genes have been identified in the human genome and mutations in
      these genes and subsequent inborn errors in aldehyde metabolism are the molecular
      basis of several diseases, including Sjogren-Larsson syndrome, type II
      hyperprolinemia, gamma-hydroxybutyric aciduria and pyridoxine-dependent seizures.
      ALDH enzymes also play important roles in embryogenesis and development,
      neurotransmission, oxidative stress and cancer. Finally, ALDH enzymes display
      multiple catalytic and non-catalytic functions including ester hydrolysis,
      antioxidant properties, xenobiotic bioactivation and UV light absorption.

PMID- 18611117
TI  - Tamsulosin modified release and oral controlled absorption system in the
      management of lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia.
AB  - BACKGROUND: Tamsulosin MR has been on the market for the treatment of lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) for
      many years. Recently, tamsulosin OCAS was introduced, which has improved
      pharmacokinetics. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin.
      METHODS: Literature was identified through a PubMed search using the term
      'tamsulosin' and by screening reference lists of review articles. RESULTS:
      Tamsulosin rapidly improves LUTS/BPH, with benefits maintained in the long-term.
      The overall tolerability of tamsulosin MR 0.4 mg is comparable to that of
      placebo. While the efficacy of tamsulosin OCAS and MR is comparable, tamsulosin
      OCAS is slightly better tolerated. CONCLUSION: Tamsulosin OCAS 0.4 mg has a
      favourable efficacy/safety profile and should be considered the treatment of
      choice for patients requiring optimal symptom control without increasing the risk
      of cardiovascular adverse events.

PMID- 18611118
TI  - Octreotide LAR for the treatment of acromegaly.
AB  - BACKGROUND: Somatostatin analogs previously considered as adjuvant therapy in
      acromegaly are increasingly used as a first-line therapy in selected cases.
      OBJECTIVE: To review the octreotide LAR pharmacological and clinical data, and
      discuss the impact of this agent on current treatment regimens. METHODS: We
      reviewed PubMed publications since the first use of octreotide LAR in acromegaly,
      and historical articles related to the discovery and development of this
      molecule. We chose, for efficacy and safety data, reviews, clinical and
      randomized controlled trials that included >or=10 patients. RESULTS/CONCLUSION:
      Octreotide LAR controls acromegaly in approximately 50-60% of patients by
      inhibiting GH and IGF-I secretion, and by reducing tumor size. This drug is well
      tolerated in most patients.

PMID- 18611119
TI  - New emerging applications of molgramostim in acute myeloid leukaemia.
AB  - BACKGROUND: Human granulocyte-macrophage colony-stimulating factor (GM-CSF)
      stimulates the proliferation and differentiation of hematopoietic progenitor
      cells in the myeloid lineage, and plays a key role in host defence and the
      inflammatory process. The main schedules adopted for clinical applications of GM
      CSF in acute myeloid leukaemia (AML) were post-chemotherapy, in order to shorten
      the duration of neutropenia, and as a mobilising agent to induce release of
      progenitor cells from bone marrow into circulation. METHODS: Based on the variety
      of biologic effects being attributed to GM-CSF, additional clinical uses for GM
      CSF have been under investigation. Concurrent administration to chemotherapy has
      been used to recruit blast cells into active cell cycle phases, and to increase
      their sensitivity to cell cycle-dependent cytotoxic drugs. RESULTS/CONCLUSION:
      Exposure to GM-CSF also has recently been shown to enhance cellular immunity and
      indirectly stimulate anti-tumour immunity. On the other hand, GM-CSF can directly
      enhance immunogenicity of tumours.

PMID- 18611120
TI  - Everolimus: an update on the mechanism of action, pharmacokinetics and recent
      clinical trials.
AB  - BACKGROUND: A growing body of evidence suggests that everolimus might offer
      effective immunosuppressive activity together with antiproliferative effects that
      may address some of the unmet needs in the long-term therapeutic management of
      the post-transplant patient. OBJECTIVE: To summarize the emerging evidence for
      employing everolimus-based immunosuppression. METHODS: A systematic review was
      conducted of the Medline, Embase and Renal Health Library (Cochrane
      Collaboration) databases, and of the summary publications from international
      transplant meetings and congresses during 2000-2008. RESULTS: This article
      summarizes this analysis, with special focus on the pharmacokinetic
      characteristics of everolimus and on the results of its use in renal
      transplantation. Some data has also been included about the efficacy of the drug
      in other solid organ transplantation and in tumours. CONCLUSIONS: Everolimus is
      an immunosuppressant drug with proven efficacy in transplantation. When used in
      combination with cyclosporin, better results are obtained in renal function with
      low cyclosporin doses. Adverse events related to this drug are frequent and lead
      to moderate dropout rates.

PMID- 18611121
TI  - Pravastatin: an evidence-based statin?
AB  - BACKGROUND: It is well known that statins lead to a markable reduction in
      cardiovascular morbidity and mortality. One of the first and best studied statins
      is pravastatin, which has been studied in both primary and secondary prevention
      trials. With 40 mg pravastatin daily, total cholesterol can be reduced by 25-34%
      with a very consistent risk reduction of 24% of death from cardiovascular
      diseases. Side effects are rare and usually consist of myopathy. Following the
      Adult Treatment Panel III (ATPIII) guidelines on cholesterol management, apart
      from therapeutic lifestyle changes, in high-risk patients (including patients
      with diabetes mellitus), cholesterol-lowering therapy should be targeted at a
      treatment goal of LDL cholesterol<2.5 mmol/l. Statin-lowering therapy should be
      commenced to adequately lower cardiovascular risk. Therefore, when the expected
      25-34% LDL cholesterol lowering would be enough to reach an LDL<2.5 mmol/l,
      treatment should be started with pravastatin. METHOD: Trials have shown that
      treatment with pravastatin is safe in older patients as well as in children with
      familial hypercholesterolemia. RESULTS/CONCLUSION: Since obesity seems to become
      a worldwide problem and given the low costs of generic pravastatin, it may even
      be cost-effectively used in developing countries.

PMID- 18611122
TI  - GADD45a-GFP GreenScreen HC genotoxicity screening assay.
AB  - BACKGROUND: Genetic toxicology is getting very interesting. The International
      Conference on Harmonisation has drafted new guidance that allows for the
      registration of pharmaceuticals without the submission of data from in vitro
      mammalian genotoxicity tests (in vitro micronucleus test, chromosomal
      aberrations, mouse lymphoma assay). These tests often produce falsely positive
      predictions of genotoxic carcinogenicity. OBJECTIVES: This article reviews the
      properties of the Gadd45a-GFP (green fluorescent protein) assay, for which
      positive results appear to provide more reliable predictions of genotoxic
      carcinogenicity. The criteria for assessment of genotoxicity assays are reviewed.
      Consideration is given to the value of genotoxicity hazard assessment early in
      pharmaceutical discovery. METHODS: Peer-reviewed data have been reviewed, as well
      as information contributed to the public domain through conference presentations.
      RESULTS/CONCLUSION: The Gadd45a assay is increasingly used as a screening tool,
      and has utility in the prioritisation of Ames-negative compounds prior to in vivo
      genotoxicity assessment.

PMID- 18611124
TI  - Health-risk behaviors and suicidal ideation: a preliminary study of cognitive and
      developmental factors.
AB  - Various theorists have suggested that unhealthy behaviors such as cigarette
      smoking and problem drinking may be subtle forms of suicidality. Consistent with
      this view, prior research has shown an association between health risk behaviors
      and suicidal ideation. In the present study we examined relationships among
      suicidal ideation, health-related attitudes and behaviors, and adverse childhood
      events. We hypothesized that unhealthy attitudes, perhaps shaped by adverse
      childhood events, would help explain the association between suicidal phenomena
      and unhealthy behaviors. Three-hundred eighteen college students completed
      surveys covering health risk behaviors, depression, suicidal ideation, and health
      related attitudes. Results supported the hypothesized associations among these
      variables. However, contrary to our hypotheses, the association between suicidal
      ideation and health-compromising behaviors was limited largely to substance
      related behaviors. Moreover, the association between suicidal ideation and health
      related attitudes was mediated by depression. Adverse childhood events were
      associated with health-related attitudes, but this relationship was mediated by
      depression. These results are less suggestive of the notion of unhealthy
      behaviors as subtle suicidality than a model in which suicidality associates
      specifically with psychopathological states such as depression and substance
      abuse. Implications for treatment and prevention programs are discussed.

PMID- 18611125
TI  - Three decades of suicide and life-threatening behavior: a bibliometric study.
AB  - The purpose of this study is to quantify certain characteristics of the articles
      published in Suicide and Life-Threatening Behavior in three 5-year periods,
      namely, 1971-1975, 1984-1988, and 1997-2001. The characteristics in question
      include geographic origin of articles, number of authors per article, number of
      references listed per article, and number of times an article is cited in the
      literature. Changes across the three periods in terms of distribution of
      subjects/participants by age group and gender are also examined. The discussion
      focuses on explanations for the trends and characteristics that are described.

PMID- 18611126
TI  - The influence of cognitive emotion regulation strategies and depression severity
      on deliberate self-harm.
AB  - Elaborating on previous studies on emotion regulation and deliberate self-harm
      (DSH), in the present study we distinguish between strategies of cognitive
      content (e.g., suicidal cognitions of perceived burdensomeness, helplessness,
      poor distress tolerance) and cognitive process (e.g., nonacceptance of emotional
      responses, lack of awareness of emotional responses). Young women who harmed
      themselves (n = 85) were compared with young women without a history of DSH (n =
      93) across a broad range of strategies. Significant group differences were found
      for all measures, even when depression severity was controlled for. In addition,
      logistic regression analyses showed that both cognitive content strategies and
      cognitive process strategies made significant independent contributions to the
      prediction of group membership. Controlling for depression severity, suicidal
      cognitions, and nonacceptance of emotional responses independently predicted DSH.
      The strong association between suicidal cognitions and DSH seems to indicate the
      important role of these cognitions in recurrent and chronic DSH. The strong
      association between nonacceptance of emotional responses and DSH underscores the
      notion that DSH can be a way to avoid emotional problems. These findings are
      discussed in relation to recent cognitive-behavioral interventions and specific
      therapeutic techniques to further insight into how these interventions might
      work.

PMID- 18611127
TI  - Mortality, or probability of death, from a suicidal act in the United States.
AB  - The probability of death resulting from a suicidal act as a function of age is
      explored. Until recently, data on suicide attempts in the United States were not
      available, and therefore the relationship between attempts and completed suicide
      could not be systematically investigated. Now, with new surveillance of self-harm
      data from the Centers for Disease Control, our examination found that (1) the
      mortality among self-harmers fits an exponential function of age and (2) the
      logarithmic difference between female and male suicidal mortality increases in
      direct proportion to age from puberty to menopause. The mortality exponential
      function of age is a description that provides a life-span perspective of suicide
      and suggests data-informed criteria for future suicide and public health
      research.

PMID- 18611128
TI  - Does marital status predict the odds of suicidal death in taiwan? A seven-year
      population-based study.
AB  - Using nationwide, 7-year population-based data for 1997-2003, we examined marital
      status to see if it predicted suicide among the ethnic Chinese population of
      Taiwan. Using cause of death data, with a case-control design, two groups-total
      adult suicide deaths, n = 17,850, the study group, and adult deaths other than
      suicide, n = 71,400 (randomly selected from age, sex, and geographic region
      matched controls, four per suicide)-were studied. Using multiple logistic
      regression analysis including age-marital status interaction, adjusted estimates
      show divorced status to be the most detrimental for suicide propensity, with
      males showing stronger effect size. Females never married, aged below 35 and 65
      plus, and widowed 65-plus had lower suicide odds.

PMID- 18611129
TI  - Correlates of Alaska Native fatal and nonfatal suicidal behaviors 1990-2001.
AB  - Factors correlated with suicidal behavior in a predominately Alaska Native region
      of Alaska are described, and the correlates relating to fatal and nonfatal
      suicide behaviors in this indigenous population are distinguished. Suicide data
      from the region (1990-2001) were aggregated and compared to 2000 U.S. Census Data
      using chi-squared tests. Multivariable logistic regression was used to identify
      predictors of suicide behaviors. Suicidal behaviors were significantly more
      common among single, unemployed Alaska Natives who had not completed high school.
      In multivariable analysis, male sex, age > or = 25 years, firearms, and substance
      abuse history were each associated with suicide death.

PMID- 18611130
TI  - Advancing prevention research on the role of culture in suicide prevention: an
      introduction.

PMID- 18611131
TI  - Developing suicide prevention programs for African American youth in African
      American churches.
AB  - Suicide prevention programs for African American youth in African American
      churches may have broad appeal because: (1) the Black Church has a strong history
      of helping community members, regardless of church membership; (2) African
      Americans have the highest level of public and private religiousness; and (3) the
      church can help shape religious and cultural norms about mental health and help
      seeking. The proposed gatekeeper model trains lay helpers and clergy to recognize
      the risk and protective factors for depression and suicide, to make referrals to
      the appropriate community mental health resources, and to deliver a community
      education curriculum. Potential barriers and suggestions for how to overcome
      these barriers are discussed.

PMID- 18611132
TI  - Suicidal behavior inLatinas: explanatory cultural factors and implications for
      intervention.
AB  - We posit that the high rates of suicidal behavior by teenage Hispanic females
      reported in large-scale surveys can be understood as a cultural phenomenon, a
      product of specific elements of the history, tradition, ideology, or social norms
      of a particular society, and that treatment interventions must take family and
      cultural factors into consideration. For over a decade, surveys have reported
      that among ethnic and racial minority youth in the United States, Latinas have
      the highest rates of suicidal behavior compared to African American and non
      Hispanic White adolescent females. However, other research shows that the
      psychological profiles of suicidal Latina adolescent girls and the risk factors
      for Latina suicidal behavior may not be that different from non-Hispanic suicidal
      adolescent females. The unique situation of adolescent Latinas involves the
      convergence of cultural and familial factors (i.e., familism, acculturation,
      relatedness, autonomy, etc.) with the developmental, social, and individual
      factors frequently associated with suicidal behaviors. Based on this background,
      family-oriented interventions appear to be the most appropriate approach to the
      prevention and treatment of Hispanic suicidal girls. Factors implicated in Latina
      suicidal behavior and community-based interventions that include the adolescent
      and her family are suggested.

PMID- 18611133
TI  - The Zuni Life Skills Development Program: a school/community-based suicide
      prevention intervention.
AB  - The Zuni Life Skills Development Program, an effective community-initiated and
      high-school-based suicide prevention intervention, is featured. Development and
      evaluation of this intervention are followed by note of the specific challenges
      associated with stabilizing the program. A more tribally diverse, culturally
      informed model entitled the American Indian Life Skills Development Curriculum is
      then presented to illustrate a hybrid approach to the cultural tailoring of
      interventions. This curriculum is broad enough to address concerns across diverse
      American Indian tribal groups yet respectful of distinctive and heterogeneous
      cultural beliefs and practices. Finally, we reflect upon issues in community
      based research that emerged during this collaboration.

PMID- 18611134
TI  - Advancing prevention research on the role of culture in suicide prevention.
AB  - Despite evidence of considerable racial/ethnic variation in adolescent suicidal
      behavior in the United States, research on youth of European American descent
      accounts for much of what is know about preventing adolescent suicide. In
      response to the need to advance research on the phenomenology and prevention of
      suicidal behavior among ethnic minority populations, NIMH co-sponsored the
      "Pragmatic Considerations of Culture in Preventing Suicide" workshop to elicit
      through interdisciplinary dialogue how culture can be considered in the design,
      development, and implementation of suicidal behavior prevention programs. In this
      discussion paper we consider the three ethnic minority suicide prevention efforts
      described in the articles appearing in this issue, along with workshop
      participants' comments, and propose six major areas where issues of culture need
      to be better integrated into suicidal behavior research.

PMID- 18611145
TI  - Transient exposure to transforming growth factor beta 3 under serum-free
      conditions enhances the biomechanical and biochemical maturation of tissue
      engineered cartilage.
AB  - A goal of cartilage tissue engineering is the production of cell-laden constructs
      possessing sufficient mechanical and biochemical features to enable native tissue
      function. This study details a systematic characterization of a serum-free (SF)
      culture methodology employing transient growth factor supplementation to promote
      robust maturation of tissue-engineered cartilage. Bovine chondrocyte agarose
      hydrogel constructs were cultured under free-swelling conditions in serum
      containing or SF medium supplemented continuously or transiently with varying
      doses of transforming growth factor beta 3 (TGF-beta3). Constructs were harvested
      weekly or bi-weekly and assessed for mechanical and biochemical properties.
      Transient exposure (2 weeks) to low concentrations (2.5-5 ng/mL) of TGF-beta3 in
      chemically defined medium facilitated robust and highly reproducible construct
      maturation. Constructs receiving transient TGF-beta3 exposure achieved native
      tissue levels of compressive modulus (0.8 MPa) and proteoglycan content (6-7% of
      wet weight) after less than 2 months of in vitro culture. This maturation
      response was far superior to that observed after continuous growth factor
      supplementation or transient TGF-beta3 treatment in the presence of serum. These
      findings represent a significant advance in developing an ex vivo culture
      methodology to promote production of clinically relevant and mechanically
      competent tissue-engineered cartilage constructs for implantation to repair
      damaged articular surfaces.

PMID- 18611146
TI  - Additive effect of RGD coating to functionalized titanium surfaces on human
      osteoprogenitor cell adhesion and spreading.
AB  - Titanium-based biomaterials for endosseous implants have found widespread
      applications in the orthopedic, maxillofacial, and dental domains. Indeed, the
      surface characteristics such as their chemical modification control considerably
      the cellular response and, subsequently, the quality and the quantity of new
      formed bone around the implant. In this study, human osteoprogenitor (HOP) cell
      adhesion on different titanium surfaces functionalized with hydroxyapatite (HA),
      type I collagen, or Arg-Gly-Asp (RGD)-containing peptides is investigated by the
      quartz crystal resonators and by confocal laser scanning microscopy (CLSM) for
      the imaging of focal contact formation. Data obtained by quartz crystal resonator
      technique revealed that RGD-containing peptides alone increase HOP cell adhesion
      in early time period of culture. Moreover, association of RGD-containing peptides
      with either type I collagen or with HA layers induces an additive effect on HOP
      cell adhesion compared to Ti-Coll or Ti-HA. CLSM shows both the area of focal
      contact by cell unit and the cytoskeleton network organization to differ
      according to the surfaces. Interestingly, association of RGD-containing peptides
      with HA layers induces an additive effect on focal contact formation on HOP cells
      compared to Ti-HA alone. These data confirm that an RGD peptide effect occurs in
      the early time of culture, which is beneficial for osteoblast to spreading,
      differentiation, and survival.

PMID- 18611147
TI  - Assessment of the suitability of chitosan/polybutylene succinate scaffolds seeded
      with mouse mesenchymal progenitor cells for a cartilage tissue engineering
      approach.
AB  - In this work, scaffolds derived from a new biomaterial originated from the
      combination of a natural material and a synthetic material were tested for
      assessing their suitability for cartilage tissue engineering applications. In
      order to obtain a better outcome result in terms of scaffolds' overall
      properties, different blends of natural and synthetic materials were created.
      Chitosan and polybutylene succinate (C-PBS) 50/50 (wt%) were melt blended using a
      twin-screw extruder and processed into 5 x 5 x 5 mm scaffolds by compression
      moulding with salt leaching. Micro-computed tomography analysis calculated an
      average of 66.29% porosity and 92.78% interconnectivity degree for the presented
      scaffolds. The salt particles used ranged in size between 63 and 125 mum,
      retrieving an average pore size of 251.28 mum. Regarding the mechanical
      properties, the compressive modulus was of 1.73 +/- 0.4 MPa (E(sec) 1%).
      Cytotoxicity evaluation revealed that the leachables released by the developed
      porous structures were not harmful to the cells and hence were noncytotoxic.
      Direct contact assays were carried out using a mouse bone marrow-derived
      mesenchymal progenitor cell line (BMC9). Cells were seeded at a density of 5 x
      10(5) cells/scaffold and allowed to grow for periods up to 3 weeks under
      chondrogenic differentiating conditions. Scanning electron microscopy analysis
      revealed that the cells were able to proliferate and colonize the scaffold
      structure, and MTS test demonstrated cell viability during the time of the
      experiment. Finally, Western blot performed for collagen type II, a natural
      cartilage extracellular matrix component, showed that this protein was being
      expressed by the end of 3 weeks, which seems to indicate that the BMC9 cells were
      being differentiated toward the chondrogenic pathway. These results indicate the
      adequacy of these newly developed C-PBS scaffolds for supporting cell growth and
      differentiation toward the chondrogenic pathway, suggesting that they should be
      considered for further studies in the cartilage tissue engineering field.

PMID- 18611148
TI  - Differences in interleukin-1 response between engineered and native cartilage.
AB  - Unlike native cartilage explants that are used in autologous tissue transfer
      procedures, engineered cartilage constructs are typically highly fragile when
      first formed and must rely on cellular activity to develop over time. However,
      inflammatory cytokines such as interleukin-1alpha (IL-1alpha) are often present
      in target joints and may interfere with this development process. Herein we
      examine to what extent nascent engineered tissue is susceptible to chemical
      perturbations by IL-1alpha (10 ng/mL), especially when compared to native
      explants, and whether in vitro preconditioning may promote sufficient integrity
      to lessen this impact. The studies were carried out using a chemically defined
      medium supplemented with or without the antiinflammatory steroid dexamethasone.
      We find that engineered tissue (bovine chondrocytes in agarose hydrogel) at early
      time points (days 0 and 14) does not grow when exposed to the cytokine even
      temporarily, but both bovine explants and more developed engineered tissue (day
      28) are able to withstand the same exposure without degradation of properties. We
      argue therefore that some in vitro preconditioning may be necessary to promote
      both sufficient mechanical integrity and the chemical fortitude without which
      insufficiently developed engineered constructs will not survive the harsh
      mechanochemical environment within the joint.

PMID- 18611149
TI  - Superficial zone protein (lubricin) in the different tissue compartments of the
      knee joint: modulation by transforming growth factor beta 1 and interleukin-1
      beta.
AB  - Superficial-zone protein (SZP), also known as lubricin, is a key mediator of
      boundary lubrication and plays an important role in the functional integrity of
      the diarthrodial joint. The aim of this investigation was to examine the role of
      transforming growth factor beta (TGF-beta) and interleukin-1 beta (IL-1beta) on
      the expression of SZP in various compartments of the bovine knee joint: the
      superficial zone of articular cartilage, synovium, meniscus, and anterior and
      posterior cruciate ligaments. The effects of TGF-beta1 and IL-1beta on SZP
      expression were examined in explants and cells from the different tissue
      compartments. TGF-beta1 up-regulated the expression of SZP in cultured explants,
      but IL-1beta down-regulated it. Quantitative analysis of secreted proteins in the
      medium of the cells demonstrated significant stimulation by TGF-beta1 and
      inhibition by IL1-beta of the accumulation of SZP protein in all four tissues.
      Real-time polymerase chain reaction analysis revealed that TGF-beta1
      significantly up-regulated SZP expression and that IL-1beta down-regulated it.
      These results revealed the modulation of SZP expression in various compartments
      of the knee joint by TGF-beta1 and IL-1beta. In addition, SZP was found to be
      immunolocalized at the surface layer of cells in histological sections of all
      four tissue compartments. Collectively, results of the current study on
      regulation of SZP expression by TGF-beta and IL-1 help provide new insights, into
      tissue engineering strategies to repair and regenerate the different tissue
      compartments in the articular joint with optimal lubrication.

PMID- 18611150
TI  - Effects of a standardized Bacopa monnieri extract on cognitive performance,
      anxiety, and depression in the elderly: a randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVES: Study aims were to evaluate effects of Bacopa monnieri whole plant
      standardized dry extract on cognitive function and affect and its safety and
      tolerability in healthy elderly study participants. DESIGN: The study was a
      randomized, double-blind, placebo-controlled clinical trial with a placebo run-in
      of 6 weeks and a treatment period of 12 weeks. SETTING/LOCATION: Volunteers were
      recruited from the community to a clinic in Portland, Oregon by public
      notification. SUBJECTS: Fifty-four (54) participants, 65 or older (mean 73.5
      years), without clinical signs of dementia, were recruited and randomized to
      Bacopa or placebo. Forty-eight (48) completed the study with 24 in each group.
      INTERVENTIONS: Standardized B. monnieri extract 300 mg/day or a similar placebo
      tablet orally for 12 weeks. OUTCOME MEASURES: The primary outcome variable was
      the delayed recall score from the Rey Auditory Verbal Learning Test (AVLT). Other
      cognitive measures were the Stroop Task assessing the ability to ignore
      irrelevant information, the Divided Attention Task (DAT), and the Wechsler Adult
      Intelligence Scale (WAIS) letter-digit test of immediate working memory.
      Affective measures were the State-Trait Anxiety Inventory, Center for
      Epidemiologic Studies Depression scale (CESD)-10 depression scale, and the
      Profile of Mood States. Vital signs were also monitored. RESULTS: Controlling for
      baseline cognitive deficit using the Blessed Orientation-Memory-Concentration
      test, Bacopa participants had enhanced AVLT delayed word recall memory scores
      relative to placebo. Stroop results were similarly significant, with the Bacopa
      group improving and the placebo group unchanged. CESD-10 depression scores,
      combined state plus trait anxiety scores, and heart rate decreased over time for
      the Bacopa group but increased for the placebo group. No effects were found on
      the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated
      with few adverse events (Bacopa n = 9, placebo n = 10), primarily stomach upset.
      CONCLUSIONS: This study provides further evidence that B. monnieri has potential
      for safely enhancing cognitive performance in the aging.

PMID- 18611152
TI  - Diagnostic accuracy of the physical examination and imaging tests for
      osteomyelitis underlying diabetic foot ulcers: meta-analysis.
AB  - Accurate diagnosis of osteomyelitis underlying diabetic foot ulcers is essential
      to optimize outcomes. We undertook a meta-analysis of the accuracy of diagnostic
      tests for osteomyelitis in diabetic patients with foot ulcers. Pooled sensitivity
      and specificity, the summary measure of accuracy (Q*), and diagnostic odds ratio
      were calculated. Exposed bone or probe-to-bone test had a sensitivity of 0.60 and
      a specificity of 0.91. Plain radiography had a sensitivity of 0.54 and a
      specificity of 0.68. MRI had a sensitivity of 0.90 and a specificity of 0.79.
      Bone scan was found to have a sensitivity of 0.81 and a specificity of 0.28.
      Leukocyte scan was found to have a sensitivity of 0.74 and a specificity of 0.68.
      The diagnostic odds ratios for clinical examination, radiography, MRI, bone scan,
      and leukocyte scan were 49.45, 2.84, 24.36, 2.10, and 10.07, respectively. The
      presence of exposed bone or a positive probe-to-bone test result is moderately
      predictive of osteomyelitis. MRI is the most accurate imaging test for diagnosis
      of osteomyelitis.

PMID- 18611153
TI  - Persistent arthralgia associated with chikungunya virus: a study of 88 adult
      patients on reunion island.
AB  - BACKGROUND: An outbreak of chikungunya virus infection occurred on Reunion Island
      during the period 2005-2006. Persistent arthralgia after chikungunya virus
      infection has been reported, but few studies have treated this aspect of the
      disease. METHODS: Adult patients with laboratory-confirmed acute chikungunya
      virus infection who were referred to Groupe Hospitalier Sud Reunion during the
      period 2005-2006 were asked to participate in the study. Patients were assessed a
      mean of 18 months after acute disease occurred. Assessment consisted of answering
      questions on a standard form, undergoing a medical examination, and being tested
      for the presence of IgM antibodies to chikungunya virus. RESULTS: Eighty-eight
      patients (mean age, 58.3 years; male-to-female ratio, 1.1:1.0) were included in
      this study. Fifty-eight patients (65.9%) had been hospitalized for acute
      chikungunya virus infection, and a history of arthralgia before chikungunya virus
      infection was reported by 39 patients (44%). Fifty-six patients (63.6%) reported
      persistent arthralgia related to chikungunya virus infection, and in almost one
      half of the patients, the joint pain had a negative impact on everyday
      activities. Arthralgia was polyarticular in all cases, and pain was continuous in
      31 patients (55.4%). Overall, 35 patients (39.7%) had test results positive for
      IgM antibodies to chikungunya virus. CONCLUSIONS: Persistent and disabling
      arthralgia was a frequent concern in this cohort of patients who had experienced
      severe chikungunya virus infection approximately 18 months earlier. Further
      studies are needed to evaluate the prevalence of persistent arthralgia in the
      general population to determine the real burden of the disease.

PMID- 18611154
TI  - Treatment outcomes for HIV-uninfected patients with multidrug-resistant and
      extensively drug-resistant tuberculosis.
AB  - BACKGROUND: Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to
      treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB,
      we assessed the treatment outcomes and prognostic factors for patients with MDR
      TB. METHODS: This study included patients who received an individualized
      treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral
      hospital in Seoul, Korea, from January 1995 through December 2004. To identify
      the prognostic factors related to favorable treatment outcomes, univariate
      comparison and multiple logistic regression were performed. RESULTS: Of 155
      patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received
      treatment with first-line drugs, and 56 (36%) had received treatment with second
      line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty
      seven patients (17%) had extensively drug-resistant (XDR) TB at the start of
      treatment. Outcome assessment revealed that 102 patients (66%) were cured or
      completed therapy. The treatment success rates did not differ significantly
      between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%).
      Surgical resection was performed more frequently for patients with XDR TB than
      for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body
      mass index >/=18.5 (calculated as the weight in kilograms divided by the square
      of the height in meters), use of >4 effective drugs, and a negative sputum smear
      result were independent predictors of a favorable outcome. CONCLUSIONS: Early
      aggressive treatment comprising at least 4 effective drugs and surgical
      resection, when indicated, may improve the outcome for patients with MDR TB or
      XDR TB.

PMID- 18611155
TI  - Low serum mannose-binding lectin level increases the risk of death due to
      pneumococcal infection.
AB  - BACKGROUND: Previous studies have shown associations between low mannose-binding
      lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However,
      MBL deficiency has not been rigorously defined, and associations with sepsis
      outcomes have not been subjected to multivariable analysis. METHODS: We
      reanalyzed MBL results in a large cohort with use of individual data from 4
      studies involving a total of 1642 healthy control subjects and systematically
      defined a reliable deficiency cutoff. Subsequently, data were reassessed to
      extend previous MBL and sepsis associations, with adjustment for known outcome
      predictors. We reanalyzed individual data from 675 patients from 5 adult studies
      and 1 pediatric study of MBL and severe bacterial infection. RESULTS: XA/O and
      O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating
      characteristic analysis revealed that an MBL cutoff value of 0.5 microg/mL was a
      reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%;
      specificity, 82%; negative predictive value, 98%). MBL deficiency was associated
      with increased likelihood of death among patients with severe bacterial infection
      (odds ratio, 2.11; 95% confidence interval, 1.30-3.43). In intensive care unit
      based studies, there was a trend toward increased risk of death among MBL
      deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90-2.77) after
      adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of
      death was increased among MBL-deficient patients with Streptococcus pneumoniae
      infection (odds ratio, 5.62; 95% confidence interval, 1.27-24.92) after
      adjustment for bacteremia, comorbidities, and age. CONCLUSIONS: We defined a
      serum level for MBL deficiency that can be used with confidence in future studies
      of MBL disease associations. The risk of death was increased among MBL-deficient
      patients with severe pneumococcal infection, highlighting the pathogenic
      significance of this innate immune defence protein.

PMID- 18611156
TI  - Understanding the complications of antiretroviral drugs.

PMID- 18611157
TI  - Acinetobacter baumannii skin and soft-tissue infection associated with war
      trauma.
AB  - BACKGROUND: Acinetobacter baumannii is usually associated with nosocomial
      pneumonia or bacteremia. Reports of A. baumannii skin and soft-tissue infection
      (SSTI) are uncommon. METHODS: We performed a retrospective review of 57
      inpatients admitted to a naval hospital ship and identified 8 patients with A.
      baumannii-associated SSTI. Demographic and clinical characteristics were compared
      between these patients and 49 patients with A. baumannii infections that were not
      SSTIs. We also reviewed 18 cases of A. baumannii-associated SSTI from the
      literature. RESULTS: Our 8 cases of A. baumannii-associated SSTI were associated
      with combat trauma wounds. The median age of the patients was 26 years. Although
      not statistically significant, A. baumannii-associated SSTIs were more likely to
      be associated with gunshot wounds (75% vs. 55%) or external fixators (63% vs.
      29%), compared with A. baumannii infections that were not SSTIs. Use of a central
      venous catheter and total parenteral nutrition was also more common for patients
      with SSTI. Our cases of A. baumannii-associated SSTI presented as cellulitis with
      a "peau d'orange" appearance with overlying vesicles and, when untreated,
      progressed to necrotizing infection with bullae (hemorrhagic and nonhemorrhagic).
      In our case series, all isolates were multidrug resistant, and clinical success
      was achieved for 7 of 8 patients with debridement and carbapenem therapy.
      CONCLUSIONS: A. baumannii-associated SSTI is an emerging infection in patients
      who experience trauma. Clinicians should be aware of the potential role of A.
      baumannii as a multidrug-resistant pathogen causing hospital-acquired SSTI,
      particularly when associated with previous trauma or use of invasive devices. It
      should be suspected in patients who experience trauma and have edematous
      cellulitis with overlying vesicles. Early empirical coverage for drug-resistant
      species (e.g., with carbapenem therapy), combined with debridement, is usually
      curative.

PMID- 18611158
TI  - Comparison of polymerase chain reaction of polymorphonuclear leukocytes and
      plasma identifies patients who control cytomegalovirus infection after
      hematopoietic cell transplantation.
AB  - By use of an automated polymerase chain reaction test of plasma and a qualitative
      polymerase chain reaction assay on polymorphonuclear leukocytes, we identified a
      subgroup of hematopoietic cell transplant recipients who were able to control
      cytomegalovirus infection early after hematopoietic cell transplantation without
      antiviral therapy. Thirty-one percent of patients had cytomegalovirus DNA
      detected by qualitative polymerase chain reaction assay but had no
      cytomegalovirus DNA detected by the automated test; this group maintained a lower
      peak cytomegalovirus load, compared with the group of patients who had
      cytomegalovirus DNA detected by both tests (P = .03), suggesting a greater degree
      of functional immune reconstitution.

PMID- 18611160
TI  - Hodgkin lymphoma-associated hemophagocytic syndrome: a disorder strongly
      correlated with Epstein-Barr virus.
AB  - The retrospective study of 34 patients with Hodgkin lymphoma-associated
      hemophagocytic syndrome led us to define this association as a specific disorder.
      Its characteristics are male predominance (male-to-female sex ratio, 3.3:1),
      immunodeficiency-like histological features (lymphocyte depletion, 45% of cases;
      mixed cellularity Hodgkin lymphoma subtype, 40%), and strong association with
      Epstein-Barr virus (94%).

PMID- 18611161
TI  - Bone of contention: diagnosing diabetic foot osteomyelitis.

PMID- 18611162
TI  - Occupational transmission of Acinetobacter baumannii from a United States
      serviceman wounded in Iraq to a health care worker.
AB  - BACKGROUND: Acinetobacter baumannii is increasingly recognized as being a
      significant pathogen associated with nosocomial outbreaks in both civilian and
      military treatment facilities. Current analyses of these outbreaks frequently
      describe patient-to-patient transmission. To date, occupational transmission of
      A. baumannii from a patient to a health care worker (HCW) has not been reported.
      We initiated an investigation of an HCW with a complicated case of A. baumannii
      pneumonia to determine whether a link existed between her illness and A.
      baumannii-infected patients in a military treatment facility who had been
      entrusted to her care. METHODS: Pulsed-field gel electrophoresis and polymerase
      chain reaction/electrospray ionization mass spectrometry, a form of multilocus
      sequencing typing, were done to determine clonality. To further characterize the
      isolates, we performed a genetic analysis of resistance determinants. RESULTS AND
      CONCLUSIONS: A "look-back" analysis revealed that the multidrug resistant A.
      baumannii recovered from the HCW and from a patient in her care were
      indistinguishable by pulsed-field gel electrophoresis. In addition, polymerase
      chain reaction/electrospray ionization mass spectrometry indicated that the
      isolates were similar to strains of A. baumannii derived from European clone type
      II (Walter Reed Army Medical Center strain type 11). The exposure of the HCW to
      the index patient lasted for only 30 min and involved endotracheal suctioning
      without use of an HCW mask. An examination of 90 A. baumannii isolates collected
      during this investigation showed that 2 major and multiple minor clone types were
      present and that the isolates from the HCW and from the index patient were the
      most prevalent clone type. Occupational transmission likely occurred in the
      hospital; HCWs caring for patients infected with A. baumannii should be aware of
      this potential mode of infection spread.

PMID- 18611163
TI  - Delaying amphotericin B-based frontline therapy significantly increases mortality
      among patients with hematologic malignancy who have zygomycosis.
AB  - BACKGROUND: Zygomycosis is an emerging opportunistic mycosis among
      immunocompromised patients with a particularly poor prognosis. METHODS: We
      analyzed the impact of delaying effective amphotericin B-based therapy on outcome
      among 70 consecutive patients with hematologic malignancy who had zygomycosis in
      our institution during the period 1989-2006. We used classification and
      regression tree analysis to identify the mortality breakpoint between early and
      delayed treatment. RESULTS: Delayed amphotericin B-based therapy (i.e.,
      initiating treatment >/=6 days after diagnosis) resulted in a 2-fold increase in
      mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9%
      vs. 48.6%); this remained constant across the years of the study and was an
      independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval,
      1.7-38.2; P = .008) in multivariate analysis. Active malignancy (P = .003) and
      monocytopenia (P =.01) at the time of diagnosis of infection were also
      independently associated with a poor outcome, whereas salvage posaconazole-based
      therapy (P=.01) and neutrophil recovery (P = .009) were predictive of a favorable
      outcome. CONCLUSIONS: Because discriminating between zygomycosis and
      aspergillosis in a timely fashion is difficult, the pursuit of aggressive
      diagnostic strategies and prompt initiation of antifungal agents with activity
      against Zygomycetes should be considered for patients with hematological
      malignancy who are at an increased risk for zygomycosis.

PMID- 18611166
TI  - Prevention of nosocomial infection and standard precautions: knowledge and source
      of information among healthcare students.
AB  - OBJECTIVE: To evaluate the knowledge of healthcare students after four curricula
      on infection control and to identify sources of information. DESIGN: Cross
      sectional study. SETTING: Four healthcare schools at Rouen University (Rouen,
      France). PARTICIPANTS: Medical students, nursing students, assistant radiologist
      students, and physiotherapist students taking public health courses. METHODS: To
      measure students' knowledge of infection control and their sources of
      information, 6 multiple-choice questions were asked about 3 specific areas:
      standard precautions, hand hygiene, and nosocomial infection. Each questionnaire
      section had 10 possible points, for an overall perfect score of 30. The sources
      of information for these 3 areas were also recorded: self-learning, practice
      training in wards, formal training in wards, and teaching during the curriculum.
      A logistic regression analysis was performed to identify factors associated with
      acceptable level of knowledge. RESULTS: Three hundred fifty students (107 medical
      students, 78 nursing students, 71 physiotherapist students, and 94 assistant
      radiologists tudents) were included in the study. The mean overall score (+/- SD)
      was 21.5 +/- 2.84. Nursing students had a better mean overall score (23.2 +/-
      2.35) than did physiotherapist students (21.9 +/- 2.36), medical students (21.1
      +/- 2.35), and assistant radiologist students (20.5 +/- 3.04; P.001). The mean
      scores ( +/- SD) for the component sections of the questionnaire were 8.5 +/- 1.4
      for standard precautions, 7.4 +/- 1.26 for hand hygiene,and 5.7 +/- 1.55 for
      nosocomial infections (P .001). The main source of information was material
      taught during the curriculum. CONCLUSION: The overall score for infection control
      indicated that instruction was effective; however, knowledge levels were
      different by area (the best scores were results of tests of standard precautions)
      and curriculum (nursing students achieved the best overall score). Ward training
      for daily infection control practice (ie, bedside instructions training and
      course work) could be improved for healthcare students.

PMID- 18611168
TI  - A quick in vitro pathway from prokaryotic genomic libraries to enzyme discovery.
AB  - Screening of prokaryotic genomes in order to identify enzymes with a desired
      catalytic activity can be performed in vivo in bacterial cells. We propose a
      strategy of in vitro expression screening of large prokaryotic genomic libraries
      based on Escherichia coli cell-free transcription-translation systems. Because
      cell-based expression may be limited by poor yield or protein misfolding, cell
      free expression systems may be advantageous in permitting a more comprehensive
      screen under conditions optimized for the desired enzyme activity. However,
      monocistronic messages with an improved leader initiation context are typically
      used for protein production in vitro. Here, we describe successful use of a
      Pseudoalteromonas genomic DNA library for in vitro expression of DNA fragments
      carrying multiple open reading frames (ORFs) in the context of their authentic
      translation initiation sites and regulatory regions. We show that ORFs located
      far from the 5' and 3' ends of polycistronic transcripts can be expressed at a
      sufficient level in an in vitro transcription-translation system in order to
      allow functional screening. We demonstrate the overall cell-free functional
      screen strategy with the successful selection of an esterase from
      Pseudoalteromonas.

PMID- 18611167
TI  - Advantages and limitations of commonly used methods to assay the molecular
      permeability of gap junctional intercellular communication.
AB  - The role of gap junctional intercellular communication (GJIC) in regulation of
      normal growth and differentiation is becoming increasingly recognized as a major
      cellular function. GJIC consists of intercellular exchange of low molecular
      weight molecules, and is the only means for direct contact between cytoplasms of
      adjacent animal cells. Disturbances of GJIC have been associated with many
      pathological conditions, such as carcinogenesis or hereditary illness. Reliable
      and accurate methods for the determination of GJIC are therefore important in
      cell biology studies. There are several methods used successfully in numerous
      laboratories to measure GJIC both in vitro and in vivo. This review comments on
      techniques currently used to study cell-to-cell communication, either by
      measuring dye transfer, as in methods like microinjection, scrape loading, gap
      fluorescence recovery after photobleaching (gap-FRAP), the preloading assay, and
      local activation of a molecular fluorescent probe (LAMP), or by measuring
      electrical conductance and metabolic cooperation. As we will discuss in this
      review, these techniques are not equivalent but instead provide complementary
      information. We will focus on their main advantages and limitations. Although
      biological applications guide the choice of techniques we describe, we also
      review points that must be taken into consideration before using a methodology,
      such as the number of cells to analyze.

PMID- 18611169
TI  - In vivo site-specific recombination using the beta-rec/six system.
AB  - The prokaryotic beta serine recombinase (beta-rec) catalyzes site-specific
      recombination between two directly oriented six sites (93 bp) in mammalian cells,
      both in episomal and in chromosomally integrated substrates. The beta-rec/six
      exclusive intramolecular site-specific recombination (SSR) system has been
      proposed as a suitable approach when several independently controlled
      recombination events are needed in a single cell. Here we explored the use of the
      beta-rec/six system for selective induction of genome-targeted modifications. We
      generated and analyzed mouse transgenic lines (Tgbeta) expressing beta-rec under
      the control of the Lck promoter. beta-rec activity was demonstrated, and there
      was no evidence of alterations to thymic or peripheral T cell development. We
      developed two transgenic mouse lines harboring different target sequences (Tgrec
      and KOsix) and analyzed the effect of beta-rec expression on these animals. The
      results indicate that the beta-rec/six SSR system is functional for in vivo gene
      targeting applications.

PMID- 18611170
TI  - Profiling the HeLa S3 transcriptome using randomly primed cDNA and massively
      parallel short-read sequencing.
AB  - Sequence-based methods for transcriptome characterization have typically relied
      on generation of either serial analysis of gene expression tags or expressed
      sequence tags. Although such approaches have the potential to enumerate
      transcripts by counting sequence tags derived from them, they typically do not
      robustly survey the majority of transcripts along their entire length. Here we
      show that massively parallel sequencing of randomly primed cDNAs, using a next
      generation sequencing-by-synthesis technology, offers the potential to generate
      relative measures of mRNA and individual exon abundance while simultaneously
      profiling the prevalence of both annotated and novel exons and exon-splicing
      events. This technique identifies known single nucleotide polymorphisms (SNPs) as
      well as novel single-base variants. Analysis of these variants, and previously
      unannotated splicing events in the HeLa S3 cell line, reveals an
      overrepresentation of gene categories including those previously implicated in
      cancer.

PMID- 18611171
TI  - Development of a DNA barcode tagging method for monitoring dynamic changes in
      gene expression by using an ultra high-throughput sequencer.
AB  - CAGE (cap analysis of gene expression) is a method for identifying transcription
      start sites by sequencing the first 20 or 21 nucleotides from the 5' end of
      capped transcripts, allowing genome-wide promoter analyses to be performed. The
      potential of the CAGE as a form of expression profiling was limited previously by
      sequencing technology and the labor-intensive protocol. Here we describe an
      improved CAGE method for use with a next generation sequencer. This modified
      method allows the identification of the RNA source of each CAGE tag within a
      pooled library by introducing DNA tags (barcodes). The method not only
      drastically improves the sequencing capacity, but also contributes to savings in
      both time and budget. Additionally, this pooled CAGE tag method enables the
      dynamic changes in promoter usage and gene expression to be monitored.

PMID- 18611172
TI  - Isolation of mitochondria from cell cultures by PCT for proteomic analysis.

PMID- 18611173
TI  - Interferon gamma: activity and ELISA detection comparisons.

PMID- 18611174
TI  - [Dermatology: a surgical subspecialty].

PMID- 18611175
TI  - Dermatology - a surgical discipline - as exemplified by surgical procedures at
      the Hospital of Munich Thalkirchner Strasse.
AB  - BACKGROUND: Despite the enormous progress in dermatosurgery during the last 35
      years,this achievement is not always appropriately acknowledged by other surgical
      specialties. We outline the significance of dermatosurgery by looking at the
      development of dermatological operations at the Department of
      Dermatology,University of Munich/Hospital of Munich Thalkirchner Strasse.
      PATIENTS AND METHODS: Data were collected and analyzed from surgery records,
      tables and from the SAP ISH-Med.The survey covered the time frame from 1971 to
      2006. RESULTS: There were 101,103 inpatient operations. The number of operations
      per year increased steadily,especially the number of medium-sized and large
      operations. A special domain of dermatosurgery is the sentinel lymph node biopsy
      in patients with malignant melanoma. In the last years, there was a continuous
      increase of patients in whom more than one tumor had to be excised. The
      percentage of patients undergoing dermatosurgery was constant at 46% of all
      inpatients. CONCLUSIONS: The surgical therapy of skin tumors is the most
      important part of inpatient treatment of dermatology patients. The development of
      dermatosurgery shows that due to the increase of skin tumors and the opening of
      new fields of activity (for example the removal of sentinel lymph nodes) there is
      a growing demand for dermatological surgeons. Solid training and competent
      representation in dermatology and attention to our interactions with other
      surgical specialties will help guarantee optimal patient care in the future.

PMID- 18611176
TI  - Food allergy.
AB  - Food allergy is defined by a specific sensitization against food allergens which
      is associated with a clinical reaction. Immediate reactions are most common and
      the skin is most often involved in food allergy. Most food allergies are IgE
      mediated although eczema reactions in atopic dermatitis and in hematogenous
      contact dermatitis to foods can be mediated by specific T-lymphocytes. Only few
      foods are responsible for the majority of most reactions in childhood. In adults
      up to 60% of all food allergic reactions are due to cross reactions between foods
      and inhalative allergens. A stepwise procedure which takes individual factors
      into account is necessary in the diagnostics of food allergy. The diagnostic
      algorithm in food allergy is not significantly different from that of other
      allergies. The oral provocation is the only method to prove food allergy in
      patients without a convincing history. A specific elimination diet is the only
      intervention which has been proven to be effective. Further therapeutic
      approaches are still under study and include specific immunotherapy, specific
      oral tolerance induction and treatment with anti-IgE antibodies.

PMID- 18611177
TI  - [Scarring, frontal alopecin in a 73-year-old woman].

PMID- 18611178
TI  - [The buried pulley stitch].

PMID- 18611180
TI  - [Saint Peregrinus as patron saint of ulcer patients].

PMID- 18611179
TI  - [Oral candidiasis].

PMID- 18611186
TI  - [In vitro drug sensitivity profiling in melanoma].

PMID- 18611188
TI  - Adipokines and cytokines in non-alcoholic fatty liver disease.

PMID- 18611190
TI  - Hyperventilation and the Pitt-Hopkins syndrome.

PMID- 18611191
TI  - The tyranny of the idea of cure (1967).
AB  - Comment on Mac Keith R. The tyranny of the idea of cure. Dev Med Child Neurol
      1967; 9: 269-70.

PMID- 18611192
TI  - Or is a children's physician just naturally nice? (1975).

PMID- 18611193
TI  - Childhood chronic daily headache: a biopsychosocial perspective.

PMID- 18611194
TI  - Amygdalar volume alterations in children with Tourette syndrome: are they due to
      ADHD comorbidity?

PMID- 18611195
TI  - Tourette syndrome, ADHD, and the limbic system: investigating the
      pathophysiology.

PMID- 18611196
TI  - Life expectancy in cerebral palsy: an update.
AB  - This paper clarifies and updates some issues of life expectancy in cerebral
      palsy. These are: (1) the definition of life expectancy and how it is calculated;
      (2) the secular trends that have occurred since the data for the 1998 paper were
      collected; (3) revised estimates reflecting improvements of some of the
      analytical methods and statistics provided in that paper; (4) comparison of life
      expectancies among countries; (5) issues regarding quality of care; and (6)
      consideration of prospective life expectations in addition to current life
      expectancy.

PMID- 18611197
TI  - The puzzle of human emotions: some historical considerations from the 17th to the
      19th centuries.
AB  - Emotions are both central to life experience itself and highly pertinent to
      various disciplines, including neuroscience, psychology, social studies,
      philosophy, and the arts. The definition of emotion lies at the interface of
      nature and culture reflecting an understanding of the components that shape
      emotional states and experiences across time and cultures. This review describes
      how the concept of emotion developed in Western thought, from the Renaissance
      notion of the passions to the 19th century idea of 'emotion'.

PMID- 18611198
TI  - Impact of congenital talipes equinovarus etiology on treatment outcomes.
AB  - Although congenital talipes equinovarus (CTEV) is often idiopathic, additional
      birth defects occur in some patients that may have an impact on the treatment of
      this disorder. The purpose of this study was to determine the prevalence of
      associated malformations, chromosomal abnormalities, or known genetic syndromes,
      and to compare treatment outcomes of children with idiopathic CTEV with children
      with non-idiopathic CTEV. Of 357 children evaluated, 273 (76%) had idiopathic
      CTEV (179 males, 94 females; mean age 2 y 1 mo [SD 1 y 2 mo], range 0-18 y) and
      84 (24%) had non-idiopathic CETV (51 males, 33 females; mean age 2 y 5 mo [SD 2
      y], range 0-16 y). Disorders affecting the nervous system were found in 46 (54%)
      children with non-idiopathic CTEV. In a subgroup of patients treated entirely at
      our institution (n=196), children with non-idiopathic CTEV (n=47) required more
      casts for correction than those with idiopathic CTEV (n=149; 5.3 vs 4.6;
      p=0.016). There was also a greater risk of recurrence in non-idiopathic CTEV
      (14.9% vs 4%; p=0.009), but no significant difference in the need for extensive
      surgery (2.7% vs 8.5%; p=0.096). Treatment was initiated at a mean age of 13
      weeks (range 1 wk to 2 y 6 mo) for both idiopathic and non-idiopathic patients,
      and treatment was assessed during a minimum 2-year follow-up. Non-idiopathic CTEV
      can be successfully treated with the Ponseti method of serial casting, with low
      recurrence rates or need for surgery.

PMID- 18611199
TI  - Results of treatment when orthopaedic surgeons follow gait-analysis
      recommendations in children with CP.
AB  - The aim of the present study was to assess the outcome of orthopaedic surgery in
      ambulant children with cerebral palsy, when the orthopaedic surgeons followed the
      recommendations from preoperative three-dimensional gait analysis. 55 children,
      mean age 10 y 11 mo, were clinically evaluated by orthopaedic surgeons who
      proposed a surgical treatment plan. After gait analysis and subsequent surgery,
      three groups were defined. In group A, there was agreement between clinical
      proposals, gait-analysis recommendations, and subsequent surgery in 128 specific
      surgical procedures. In group B, 54 procedures were performed based on gait
      analysis, although these procedures had not been proposed at the clinical
      examination. In group C, 55 surgical procedures that had been proposed after
      clinical evaluation were not performed because of the gait-analysis
      recommendations. The children underwent follow-up gait analysis 1 to 2 years
      after the initial analysis. The kinematic results were satisfactory, with
      improvement in most of the gait parameters in children who had undergone surgery
      and no significant deterioration in those who were not operated. In group A,
      there were significant improvements in maximum hip extension in stance, minimum
      knee flexion in stance, timing of maximum knee flexion in swing and knee range of
      motion, maximum ankle dorsiflexion in stance, and mean femur rotation in stance.
      In group B, there were significant improvements in maximum hip extension in
      stance, minimum knee flexion in stance, and knee range of motion. We conclude
      that gait analysis was useful in confirming clinical indications for surgery, in
      defining indications for surgery that had not been clinically proposed, and for
      excluding or delaying surgery that was clinically proposed.

PMID- 18611200
TI  - Impact of modafinil on spasticity reduction and quality of life in children with
      CP.
AB  - This randomized double blind AB/BA cross-over trial evaluates the effect of oral
      modafinil versus placebo on spasticity, function, and quality of life in children
      with cerebral palsy (CP). Outcomes were measured at the start and end of both 8
      week treatment periods (modafinil and placebo). The order of the treatment
      periods was randomly assigned. There was a 4-week wash-out period between
      treatments. Primary outcomes include the Modified Ashworth Score (MAS), and the
      Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD),
      a disorder-specific quality of life measure. Ten children were randomized and
      eight children completed the study. The mean age of participants was 11 years 5
      months (SD 1 y 5 mo, range 8 y 8 mo-12 y 11 mo). Five of the participants were
      male and three female. Seven children had a diagnosis of spastic quadriplegic CP
      and one child had spastic diplegia with overflow tone to the upper extremities.
      The Gross Motor Function Classification System ranged from Level III to V with
      one child at Level III, six children at Level IV, and one at Level V. The CPCHILD
      pre- to post-total scores showed a slight improvement in quality of life during
      the placebo period and a slight deterioration in the modafinil period (overall
      mean change of 7.1, SD 7.6). A t-test between post differences was statistically
      significant (t=2.65, p=0.03) in favor of the placebo period. The MAS for elbow
      flexors, ankle flexors, and hip adductors did not show any significant reduction
      post-modafinil or post-placebo (p values ranged from 0.41-0.79). This study did
      not find evidence that modafinil reduces spasticity or has a positive impact on
      quality of life in children with spastic CP.

PMID- 18611201
TI  - Skeletal maturation in children with cerebral palsy and its relationship with
      motor functioning.
AB  - The objective of this study was to describe skeletal maturation in relation to
      chronological age in children with cerebral palsy (CP) aged 9 to 16 years, and to
      analyze the relationship between skeletal maturation and motor functioning. The
      skeletal age of 100 children with CP (37 females, 63 males; age 9, 11, or 13 y;
      73 ambulant, 27 non-ambulant) was determined over a period of 3 years based on X
      rays of the hand (Greulich and Pyle technique). Motor functioning was measured
      with the Gross Motor Function Measure-66. The skeletal age of females with CP was
      significantly higher than their chronological age, but this did not apply to
      males. Longitudinal analysis showed no difference in the course of skeletal age
      in relation to chronological age over a 3-year period for sex or for level of
      ambulation. No association was found between changes in skeletal age and changes
      in gross motor function over the 3-year period. Skeletal age during (pre-)puberty
      in females with CP is advanced in relation to chronological age. No evidence was
      found that children with CP are at risk for deterioration in gross motor function
      as a result of skeletal maturation during puberty.

PMID- 18611202
TI  - Quantifying weight bearing while in passive standers and a comparison of
      standers.
AB  - Mechanical loading plays an important role in skeletal health, and this is a
      major reason standing devices are widely used with non-ambulatory persons.
      However, little is known about the true axial loading that occurs while in a
      stander, or the factors which may impact loading. The purpose of this study was
      to quantify weight borne while in a stander, and to directly compare different
      standers. Load measuring footplate adaptors were designed and fabricated
      specifically for this study. Weight bearing loads in 20 non-ambulatory persons
      with quadriplegic cerebral palsy aged 6 to 21 years (median 14 y) were
      continuously monitored during routine 30-minute standing sessions. Fourteen
      participants were female, six were male; one was Gross Motor Function
      Classification System (GMFCS) Level IV, and 19 were GMFCS Level V. Each
      participant was monitored on four to six occasions over an 8-week period, two to
      three times in each of two different standers (total 108 standing sessions).
      Weight bearing loads ranged widely from 37 to 101% of body weight. The difference
      between standers was as much as 29% body weight. There is wide variance in the
      actual weight borne while in passive standers. The type of stander utilized is
      one factor which can significantly affect the amount of weight borne.

PMID- 18611203
TI  - Are amygdalar volume alterations in children with Tourette syndrome due to ADHD
      comorbidity?
AB  - Recent studies have shown that changes in the basal ganglia circuitry and limbic
      loops may play an important role both in Tourette syndrome (TS) and attention
      deficit-hyperactivity disorder (ADHD). This study aimed to investigate in vivo
      possible morphological alterations of the amygdala as a key component of the
      limbic system. Amygdalar and total brain volumes were measured in three
      dimensional magnetic resonance imaging data sets of 17 male patients with TS
      (mean age 11 y 8 mo [SD 2 y]; range 9-16 y) and 17 age-matched comparison
      children (mean age 12 y 6 mo (SD 2 y 1 mo); range 9-17 y) by volume-of-interest
      based volumetry. Eight members of the TS group also fulfilled the diagnostic
      criteria for ADHD. A significant decrease in the left-hemispheric amygdalar
      volumes and in the proportions of amygdalar to total brain volumes was observed
      in members of the TS group compared with the comparison group. Amygdalar volumes
      did not correlate with tic severity, but with behavioural impairment and
      especially with symptoms of ADHD. The amygdalar volume reduction might be the
      pathoanatomical correlate of an impaired input of the amygdala to the striatum
      and frontal cortex. Future studies should investigate if the involvement of the
      amygdala is due to TS or rather caused by the genetically-linked most frequent
      comorbidity ADHD.

PMID- 18611204
TI  - The combined burden of cognitive, executive function, and psychosocial problems
      in children with epilepsy: a population-based study.
AB  - The combined burden of psychosocial (Achenbach scales), cognitive (Raven
      matrices), and executive function (EF) problems was studied in a population-based
      sample of 6- to 12-year-old children with epilepsy (n=162; 99 males, 63 females)
      and in an age- and sex-matched control group (n=107; 62 males, 45 females).
      Approximately 35% of the children with epilepsy had severe non-verbal cognitive
      problems. In those that did not, mild cognitive problems (26% vs 11%, p=0.005),
      EF problems (31% vs 11%, p<0.001), and psychosocial problems (45% vs 10%,
      p<0.001) were each much more common than among controls. Having problems in two
      or all three of these areas simultaneously was more frequent among the children
      with epilepsy (14% vs. 3%, p<0.001 and 4% vs 0%, p<0.001 respectively). Excluding
      those having remote symptomatic epilepsy aetiology did not change the problem
      load significantly for the children with epilepsy with the important exception
      that having severe non-verbal problems was approximately halved from 35 to 18%.
      In 30 children with benign epilepsy of childhood with centrotemporal spikes, mild
      cognitive problems were somewhat more common, but psychosocial and EF problems
      were similar compared with control children.

PMID- 18611205
TI  - Delays in investigation and management of acute arterial ischaemic stroke in
      children.
AB  - The aim of this study was to investigate the timing and course of investigation
      and diagnosis in children with acute arterial ischaemic stroke (AIS) and factors
      influencing this using a retrospective case-note review. Participants comprised
      50 children (26 males, 24 females; median age at presentation 3 y 4 mo, range 2
      mo-16 y 10 mo). Although all had brain infarction, symptoms resolved in less than
      24 hours in 21 children (transient ischaemic attack [TIA] group). Thirty-seven
      children saw a doctor within 6 hours of the attack; 32 did not see a paediatric
      neurologist until after 24 hours. Initial neuroimaging (computed tomography or
      magnetic resonance imaging) occurred in less than 6 hours in 13/46 children and
      in more than 24 hours in 18/46 children. Brain magnetic resonance imaging
      occurred in more than 24 hours in 43/47 children. Time to clinical diagnosis
      (data available on 42 children) was less than 6 hours in 14 children, 6 to 12
      hours in six, 12 to 24 hours in eight, and more than 24 hours in 14 children. In
      multiple regression analysis, patients with stroke were more likely to have
      shorter time to diagnosis than those with TIA. Our results show that most
      children with acute AIS are seen within 6 hours but definitive imaging and
      specialist assessment take more than 24 hours. Time to diagnosis is significantly
      longer in children with TIA (p=0.001). Trials of acute treatment being designed
      for childhood AIS will require rapid transfer to tertiary centers and access to
      definitive neuroimaging, but these data suggest that this will challenge existing
      practice.

PMID- 18611206
TI  - Childhood chronic daily headache: a biopsychosocial perspective.
AB  - The aim of our observational study was to highlight some clinical observations on
      chronic daily headache (CDH) in children and adolescents. Data on patients < or
      =18 years aged presenting with CDH to the Pediatric Headache Clinic at the Royal
      University Hospital, Saskatoon, Canada, were collected prospectively and
      sequentially from February 2004 to July 2006. Standardized data sheets and
      definitions were used. Follow-up information on the 70 participants (22 males, 48
      females) was current to February 2007. Fifty-four participants (77%) had had
      recurrent headaches before transformation to CDH. Comorbid chronic migraine and
      chronic tension-type headache was the most frequent subtype of CDH (37
      participants; 53%). Anxiety and mood disorders were diagnosed in 17 and 15
      children respectively. Stressors that precipitated or contributed to the
      maintenance of CDH were judged important in 44 (63%). The possibility of a
      somatoform disorder was considered in five children, a factitious disorder in
      one, and malingering in another. We suggest that CDH be viewed from a
      biopsychosocial rather than a narrow biomedical perspective and the
      classification improved to enhance clinical utility.

PMID- 18611207
TI  - Pain and activity limitations in children with Duchenne or Becker muscular
      dystrophy.
AB  - The purpose of this study was to examine the prevalence and characteristics of
      pain in children with Duchenne (DMD) or Becker (BMD) muscular dystrophy,
      including the nature of disagreements concerning pain symptoms among children,
      parents, and physicians, and limitations in daily activities. Male children (age
      8-18 y, n=53) and parents (n=53) completed questionnaires assessing pain
      intensity (visual analogue scale), pain frequency (Likert scale [LS]), pain
      duration (LS), emotional distress due to pain (LS), and pain location (body
      outline markings). The Child Activity Limitations Interview was also completed by
      both raters to assess daily activities that are limited by recurrent pain.
      Physicians completed a form indicating medical history and pain symptoms. The
      majority of children with DMD (mean age 13 y 11 mo [SD 3.38]; range 8-18 y) or
      BMD (mean 14 y 10 mo [SD 1.48]; range 12-17 y) were non-ambulatory (79 and 50%
      respectively) and experienced pain according to self (54-80%) and parent reports
      (70-90%). Pain typically occurred at least once per week and was of mild to
      moderate intensity. Most children experienced pain for less than a few hours and
      little to moderate levels of emotional distress due to pain. Pain occurred in the
      lower back, spine, and legs, and was described as 'aching'. Children and parents
      indicated significantly more intense pain than the physician. Actual agreement
      between parent and child report on pain symptoms was poor to fair. Pain is a
      common occurrence in children with DMD or BMD, yet may be under-recognized. Pain
      assessment needs to be a standard part of care and may identify difficulties
      faced by these children to be targeted by interventions.

PMID- 18611208
TI  - Progressive hemispheric shrinking in hemimegalencephaly: a possible role for
      seizure-related neuronal loss.
AB  - Hemimegalencephaly (HME) is a developmental brain lesion consisting of a
      unilateral enlarged, dysplastic, and often highly epileptogenic cerebral
      hemisphere. Most patients exhibit early onset intractable seizures, status
      epilepticus, hemiplegia, hemianopsia, and developmental delay. Major surgical
      procedures are advocated for limiting the devastating consequences of epilepsy.
      We studied a female with HME, early onset intractable seizures and recurrent
      status epilepticus, in whom progressive hemiatrophy of the enlarged hemisphere
      and normal growth of the contralateral hemisphere, exceeding the size of the
      dysplastic hemisphere, was demonstrated by magnetic resonance imaging.
      Histopathology, following functional hemispherectomy at the age of 7 years,
      demonstrated severe neuronal loss with an elevated number of cells exhibiting the
      morphological and biochemical features of apoptosis. Eighteen months after
      surgery the patient was seizure-free (Engel class I) and exhibited improved motor
      and language skills, alertness and social behaviour. We hypothesize that nearly
      continuous seizure activity might sustain seizure-induced brain injury in the
      dysplastic hemisphere but causal heterogeneity and associated anatomical factors
      may influence differently the individual predisposition to atrophic changes.

PMID- 18611209
TI  - Melatonin--an orphan drug.

PMID- 18611210
TI  - Ecological strategies to promote healthy body image among children.
AB  - BACKGROUND: Personal habits of children and adolescents related to healthy body
      image (BI) are influenced by various determinants in the micro- and
      macroenvironment. These include attitudes and behaviors about eating; exercise
      and physical appearance modeled by parents, teachers, and peers; as well as
      opportunities to learn new habits and social praise for healthy choices. The
      coordinated school health program (CSHP) is compatible with the 5 levels of an
      ecological approach to developing new health behaviors. METHODS: Authors
      systematically applied the ecological model to all 8 components of coordinated
      school health. Next, strategies for each of the components were developed using
      the professional literature as well as author expertise in the areas of health
      education, exercise science, and dietetics. RESULTS: For each strategy,
      applicable health and physical education standards, as well as goals for each
      strategy and additional Web resources, were provided to assist educators and
      administrators in supporting healthy BI among students. CONCLUSIONS: Educators
      may effectively use a coordinated approach to guide multiple intervention
      activities aimed at increasing healthy habits among adolescents and their
      families. The strength of the CSHP is its collaborative nature with active
      participation by students, faculty members, family caregivers, agency
      professionals, community residents, and health care providers.

PMID- 18611211
TI  - Linking Global Youth Tobacco Survey 2003 and 2006 data to tobacco control policy
      in India.
AB  - BACKGROUND: India made 2 important policy statements regarding tobacco control in
      the past decade. First, the India Tobacco Control Act (ITCA) was signed into law
      in 2003 with the goal to reduce tobacco consumption and protect citizens from
      exposure to secondhand smoke (SHS). Second, in 2005, India ratified the World
      Health Organization Framework Convention on Tobacco Control (WHO FCTC). During
      this same period, India conducted the Global Youth Tobacco Survey (GYTS) in 2003
      and 2006 in an effort to track tobacco use among adolescents. METHODS: The GYTS
      is a school-based survey of students aged 13-15 years. Representative national
      estimates for India in 2003 and 2006 were used in this study. RESULTS: In 2006,
      3.8% of students currently smoked cigarettes and 11.9% currently used other
      tobacco products. These rates were not significantly different than those
      observed in 2003. Over the same period, exposure to SHS at home and in public
      places significantly decreased, whereas exposure to pro-tobacco ads on billboards
      and the ability to purchase cigarettes in a store did not change significantly.
      CONCLUSIONS: The ITCA and the WHO FCTC have had mixed impacts on the tobacco
      control effort for adolescents in India. The positive impacts have been the
      reduction in exposure to SHS, both at home and in public places. The negative
      impacts are seen with the lack of change in pro-tobacco advertising and ability
      to purchase cigarettes in stores. The Government of India needs to consider new
      and stronger provisions of the ITCA and include strong enforcement measures.

PMID- 18611212
TI  - Concurrent psychosocial predictors of sun safety among middle school youth.
AB  - BACKGROUND: Sun-induced skin damage, which increases skin cancer risk, is
      initiated in early life and promoted through later sun exposure patterns. If sun
      safety determinants are well understood and addressed during the school years,
      skin cancer incidence might be reduced. This study tested psychosocial influences
      on youth's sun safety and assessed their strength within and across gender and
      ethnicity in a sample of 1782 middle school students. METHODS: Predictors
      included sunburn and skin cancer knowledge, tanning attitudes, peer norms, and
      barriers regarding sun exposure and were assessed with a self-administered,
      validated questionnaire. The hypothesized relationships were tested with
      structural equation models and confirmed with multilevel regression. RESULTS:
      Across gender and ethnicity, knowledge emerged as an important sun safety
      predictor with both direct and indirect effects mediated through tanning
      attitudes. The relationship with barriers did not reach statistical significance
      within any of the subgroups, possibly due to measurement limitations. An indirect
      effect of peer norms on sun safety, mediated through tanning attitudes, was
      confirmed only among girls. Also, an indication that peer norms operate
      differently within the ethnic groups was found, since this predictor had a
      statistically significantly stronger relationship with sun safety among non
      Hispanics. CONCLUSIONS: Youth's sun safety is a multifactorial practice,
      partially determined by ethnicity- and gender-based standards. In order to ensure
      health-promoting school environments, needed are multicomponent programs where
      peer norms and knowledge are salient and where sun safety is addressed
      individually and together with other health risk behaviors.

PMID- 18611213
TI  - Sexually transmitted infection among adolescents receiving special education
      services.
AB  - BACKGROUND: To estimate the relative risk of sexually transmitted infections
      (STIs) among children identified as having learning disabilities through the
      special education system. METHODS: This cross-sectional study used special
      education data and Medicaid data from Philadelphia, Pennsylvania, for calendar
      year 2002. The sample comprised 51,234 Medicaid-eligible children, aged 12-17
      years, 8015 of whom were receiving special education services. Claims associated
      with diagnoses of STIs were abstracted, and logistic regression was used to
      estimate the odds of STI among children in different special education
      categories. RESULTS: There were 3% of males and 5% of females who were treated
      for an STI through the Medicaid system in 2002. Among females, those in the
      mental retardation (MR) category were at greatest risk (6.9%) and those in the
      emotionally disturbed or "no special education" category at lowest risk (4.9%
      each). Among males, STIs were most prevalent among those classified as mentally
      gifted (6.7%) and lowest among those in the MR category (3.0%). In adjusted
      analyses, males with specific learning disabilities and females with MR or who
      were academically gifted were at excess risk for STIs. CONCLUSIONS: The finding
      that children with learning disabilities are at similar or greater risk for
      contracting STIs as other youth suggests the need to further understand their
      risk behaviors and the potential need to develop prevention programs specific to
      their learning needs.

PMID- 18611214
TI  - Students with chronic diseases: nature of school physician support.
AB  - BACKGROUND: To educate children with chronic diseases in the least restrictive
      environment, schools must prevent, recognize, and react appropriately to symptom
      exacerbations. Schools are often pushed to their limits of knowledge, resources,
      and comfort level. This study determined the health conditions of students for
      whom districts seek school physician consultation and the nature of school
      physician consultants' involvement. METHODS: A retrospective record review was
      performed on 250 of the most recent records of school-elicited referrals from an
      academic center that provides physician consultation to school districts.
      Referrals were sent from 8 school districts in southern California (July 1996 to
      October 2006). Data collected were nature of student's special health need, the
      school physician consultant's intervention required to satisfy schools' needs,
      student grade level, enrollment in special education, and health-related
      excessive absenteeism. RESULTS: No single chronic condition, symptom, or special
      health care need predominated. Six types of school physician consultant
      activities were used to overcome hurdles schools faced when accommodating
      students with special health care needs. The 3 most common were direct
      communication with students' own physicians (70% of students), recommending an
      appropriate level of school health services when this was a matter of controversy
      (42%), and formulating portions of students' individualized school health plans
      (38%). CONCLUSIONS: A portion of students with special health care needs
      benefited from district referral to a school physician consultant. Whether some
      of these referrals can be avoided if school personnel and students' own
      physicians are supported and trained to communicate more effectively with one
      another needs to be explored.

PMID- 18611215
TI  - Is immigrant status relevant in school violence research? An analysis with Latino
      students.
AB  - BACKGROUND: The role of race and ethnicity is consistently found to be linked to
      the likelihood of students experiencing school violence-related outcomes;
      however, the findings are not always consistent. The variation of likelihood, as
      well as the type, of student-related school violence outcome among the Latino
      student population may be attributed to immigrant status. METHODS: Drawing from
      the Education Longitudinal Study of 2002, this research investigates if the role
      of immigrant status and English proficiency are pertinent for 1457 nationally
      representative public school Latino students' experiences with school violence
      related outcomes. RESULTS: Third-generation immigrant students were more likely
      than first- and second-generation students to be victimized while at school, as
      well as receive a formal disciplinary school sanction. On the other hand, first
      generation immigrant children were less likely to be a victim of crime while at
      school and receive a formal disciplinary sanction in comparison to second- and
      third-generation immigrants. However, first-generation immigrant students were
      the most likely to feel unsafe at school. Additionally, nonnative English
      speaking students were more likely to report being a victim of school violence in
      comparison to native English speakers. CONCLUSIONS: This study indicates that
      immigrant status-related variables should be included in school violence
      research. Furthering the investigation of school and local community
      characteristics of immigration and assimilation and their impact upon children's
      lives and their exposure to violence is essential for a growing immigrant
      population.

PMID- 18611216
TI  - The impact of mild central auditory processing disorder on school performance
      during adolescence.

PMID- 18611218
TI  - Serpentine and non-serpentine ecotypes of Collinsia sparsiflora associate with
      distinct arbuscular mycorrhizal fungal assemblages.
AB  - Although plant adaptation to serpentine soils has been studied for several
      decades, the mechanisms of plant adaptation to edaphic extremes are still poorly
      understood. Arbuscular mycorrhizal fungi (AMF) are common root symbionts that can
      increase the plant hosts' establishment and growth in stressful environments.
      However, little is known about the role plant-AMF interactions play in plant
      adaptation to serpentine. As a first step towards understanding this role, we
      examined the AMF assemblages associated with field populations of serpentine and
      non-serpentine ecotypes of California native plant Collinsia sparsiflora. We
      sampled roots of C. sparsiflora from three serpentine and three non-serpentine
      sites in close proximity (110 m to 1.94 km between sites) and analysed the small
      subunit ribosomal DNA gene amplified from root DNA extracts using AMF-specific
      primers. A total of 1952 clones from 24 root samples (four from each site) were
      sequenced. We used sequence similarity and phylogenetic analysis to determine
      operational taxonomic units (OTU) resulting in 19 OTUs representing taxa from six
      AMF genera, including one serpentine-specific OTU. We used Bray-Curtis
      similarity, multidimensional scaling and analysis of similarity to compare root
      sample AMF assemblages. These analyses clearly showed that plant ecotypes
      associated with distinct AMF assemblages; an Acaulospora OTU-dominated
      serpentine, and a Glomus OTU-dominated non-serpentine assemblages. Species
      diversity and evenness were significantly higher in serpentine assemblages.
      Finally, relate analysis showed a relationship between ecotype AMF assemblages
      and soil nutrients. This study reveals a strong relationship between AMF
      associates and plant adaptation to edaphic extremes.

PMID- 18611220
TI  - Development of broad-spectrum halomethyl ketone inhibitors against coronavirus
      main protease 3CL(pro).
AB  - Coronaviruses comprise a large group of RNA viruses with diverse host
      specificity. The emergence of highly pathogenic strains like the SARS coronavirus
      (SARS-CoV), and the discovery of two new coronaviruses, NL-63 and HKU1,
      corroborates the high rate of mutation and recombination that have enabled them
      to cross species barriers and infect novel hosts. For that reason, the
      development of broad-spectrum antivirals that are effective against several
      members of this family is highly desirable. This goal can be accomplished by
      designing inhibitors against a target, such as the main protease 3CL(pro)
      (M(pro)), which is highly conserved among all coronaviruses. Here 3CL(pro)
      derived from the SARS-CoV was used as the primary target to identify a new class
      of inhibitors containing a halomethyl ketone warhead. The compounds are highly
      potent against SARS 3CL(pro) with K(i)'s as low as 300 nM. The crystal structure
      of the complex of one of the compounds with 3CL(pro) indicates that this
      inhibitor forms a thioether linkage between the halomethyl carbon of the warhead
      and the catalytic Cys 145. Furthermore, Structure Activity Relationship (SAR)
      studies of these compounds have led to the identification of a pharmacophore that
      accurately defines the essential molecular features required for the high
      affinity.

PMID- 18611223
TI  - Strengthening acceptance for xenotransplantation: the case of attraction effect.
AB  - BACKGROUND: Despite being still at the experimental level, xenotransplantation
      may become an effective strategy to overcome the scarcity of human organs.
      However, at the present time there is considerable resistance to this kind of
      biomedical technology. The aim of the present study was to identify novel
      strategies to reduce patients' negative affective reactions towards
      xenotransplantation helping them to understand the advantages of
      xenotransplantation in a more analytical fashion and increase their acceptance
      for this approach. METHODS: The study was conducted in a group of patients with
      liver cirrhosis waiting for liver transplantation. They were presented with
      hypothetical scenarios and asked to choose among either two or three alternative
      types of donor defined by their species (e.g., livers from humans vs. other
      species) and availability (low for human donors and high for livers from non
      human species). RESULTS: Patients were unwilling to accept xenotransplantation if
      they were presented with livers from humans (chosen by 97.5% of participants) vs.
      livers from genetically modified pigs (2.5%). On the other hand, a different
      group of patients was significantly more willing to accept xenotransplantation if
      they were presented with three different types of donors: respectively, human
      beings (74.4%), genetically modified pigs (25.6%) and genetically modified dogs.
      In addition, human livers were judged significantly more attractive than
      genetically modified livers from pigs, monkeys, dogs, or sheep and pig livers
      were rated as significantly more attractive than livers from monkeys, dogs, or
      sheep (for all comparisons P < 0.01). CONCLUSIONS: These results demonstrate that
      paradigms from other fields, like decision-making, might help to communicate more
      effectively the potential of xenotransplantation, modulating patients' affective
      reactions and allowing them to understand the potential strengths of this
      biomedical technology.

PMID- 18611224
TI  - Prolongation of corneal xenotransplant survival by T-cell vaccination-induced T
      regulatory cells.
AB  - BACKGROUND: Corneal xenotransplantation is an alternative approach for overcoming
      shortage of allograft in clinics. However, the mechanism of acute corneal
      xenograft rejection and the method of prolonging xenograft survival have not been
      well defined. METHODS: In this study, we used an orthotopic corneal guinea pig-to
      rat xenotransplantation model to study the effects of CD4 and CD8 T cells, T-cell
      vaccination (TCV) and TCV-induced T-regulatory (Treg) cells on xenograft
      survival. RESULTS: The acute rejection of xenografts occurred in untreated rats
      as early as 6 days post-transplantation, while TCV significantly prolonged
      xenograft survival from 6-12 to 21-27 days. The lymph node cells of the TCV
      treated rats exhibited significant response to the anti-guinea pig T cells and
      the responding cell populations contained two Treg cell subsets, CD4+ CD25- and
      CD8+ CD28- T cells, both of which lack expression of Foxp3. Adoptive transfer of
      CD8+ CD28- T cells resulted in profound inhibition of corneal xenograft
      rejection, while transfer of CD4+ CD25- T cells alone exhibited no significant
      inhibition. However, transfer of the CD4+ CD25- and CD8+ CD28- T-cell mixture
      remarkably enhanced the in vivo protective activity against xenograft rejection.
      CONCLUSIONS: These data suggest that TCV induces the activation of specific Treg
      cell subsets, CD4+ CD25- and CD8+ CD28- T cells, which may act cooperatively to
      mediate prolongation of corneal xenograft survival. Therefore, TCV can be used as
      immunotherapy for suppression of acute xenograft rejection.

PMID- 18611225
TI  - Local expression of IDO, either alone or in combination with CD40Ig, IL10 or
      CTLA4Ig, inhibits indirect xenorejection responses.
AB  - BACKGROUND: To overcome cell-mediated xenorejection by transgenic expression of
      immunomodulatory molecules by a graft, it is likely that expression of multiple
      molecules will be required. Previous studies support the use of the
      immunomodulatory agents indoleamine 2,3-dioxygenase (IDO), CD40Ig, interleukin 10
      (IL10), and CTLA4Ig for suppression of rejection responses. We examined the
      effects of local expression of these molecules by a porcine cell line (PIEC) on
      indirect murine xenorejection responses in vitro and in vivo. METHODS: The PIEC
      stable lines expressing IDO, CD40Ig, and IL10 as single molecules were generated.
      In addition, PIEC lines expressing IDO with either CD40Ig, IL10 or CTLA4Ig were
      generated to produce cell lines expressing two molecules. BALB/c mice were primed
      with wild type PIEC, followed by harvesting splenocytes used as responder cells
      and PIEC expressing immunomodulatory molecules as stimulators, in proliferation
      and cytokine assays. In vivo effects of modified PIEC were examined by
      transplantation of PIEC lines expressing the immunomodulatory molecules under the
      renal capsule of naive mice. PIEC grafts were harvested for histological
      evaluation at days 7 and 14. RESULTS: Proliferation of primed BALB/c splenocytes
      was inhibited most significantly by IDO compared with control cells (49%, P =
      0.02). In addition both Th1 (interferon-gamma) and Th2 (IL4 and IL10) cytokines
      were markedly inhibited in vitro by IDO expression. IL10 expressing cells did not
      inhibit proliferation as potently (37%, P = 0.03) whilst CD40Ig lead to an
      increase in proliferative responses (59%, P = 0.02). Co-expression of CD40Ig,
      IL10, and CTLA4Ig with IDO resulted in further modest reductions in proliferation
      compared with IDO expression alone. When transplanted under the renal capsule of
      BALB/c mice, those grafts expressing IDO demonstrated significantly lower levels
      of lymphocyte infiltration at days 7 and 14 than control grafts and those
      expressing CD40Ig, CTLA4Ig or IL10 alone. Grafts co-expressing IDO and a second
      molecule were no better protected than those expressing IDO alone. Graft cell
      viability (PIECs) was reduced in some IDO expressing grafts suggesting high
      levels of IDO expression may inhibit PIEC viability, however, grafts co
      expressing IDO-CTLA4Ig and IDO-IL10 were not affected in this way. CONCLUSION:
      Indoleamine 2,3-dioxygenase appears to be a potent molecule for protecting
      xenografts from cell-mediated rejection responses activated via the indirect
      pathway. Co-expression of IDO with both CTLA4Ig and IL10 warrants further
      investigation. Overall these findings support pursuing further studies, in larger
      animal models, to determine whether increased IDO activity within the graft
      itself can attenuate xenorejection responses.

PMID- 18611226
TI  - Experimental multivisceral xenotransplantation.
AB  - BACKGROUND: Organ shortage impairs the proposition of multivisceral
      transplantation to treat multiple organ failure. Interspecies (xeno)
      transplantation is a valid solution for organ shortage; however, suitable models
      of this advance are lacking. We describe an effective model of multivisceral
      xenotransplantation to study hyperacute rejection. METHODS: Under general
      anesthesia, we in block recovered the distal esophagus, stomach, small bowel,
      colon, liver, pancreas, spleen, and kidneys from donors and implanted
      heterotopically in the lower abdomen of recipients. Animals were divided into
      four groups: I-canine donor, swine recipient (n = 6); II - swine donor, canine
      recipient (n = 5); III-canine donor, canine recipient (n = 4); and IV-swine
      donor, swine recipient (n = 5). Groups I and II comprised experimental
      (xenotransplantation) and III and IV control groups (allotransplantation). During
      the experiment, we appraised recipient evolution and graft modification by
      sequential biopsy up to 3 h. At this time, we killed animals for autopsy
      (experimental end point). RESULTS: We accomplished all experiments successfully.
      Every grafts attained customary appearance and convenient urine output
      immediately after unclamp. Around 15 min after reperfusion, xenografts achieved
      signs of progressive hyperacute rejection and absence of urine output. At the end
      of experiments we observed moderate to severe hyperacute rejection at small
      bowel, colon, mesenteric lymph node, liver, spleen, pancreas, and kidney, while
      stomach and esophagus achieved mild lesions. In contrast, allograft achieved
      normal or minimum ischemia/reperfusion injury and constant urine output.
      CONCLUSION: The present procedure assembles a simple and effective model to study
      multivisceral xenotransplantation and may ultimately spread researches toward
      hyperacute rejection.

PMID- 18611227
TI  - Recombinant pig TFPI efficiently regulates human tissue factor pathways.
AB  - Rejected pig-to-primate organ xenografts almost invariably exhibit significant
      microvascular thrombosis, believed to be due in part to several molecular
      incompatibilities affecting the regulation of coagulation. In this study, we
      tested one such proposed incompatibility: whether there is, at least in part, a
      functional incompatibility in pig tissue factor pathway inhibitor (TFPI) that
      impedes binding of human factor Xa and regulation of human tissue factor
      initiated coagulation. TFPIalpha cDNA was cloned from pig aortic endothelial
      cells and found to encode a 279-residue mature protein with 79% overall identity
      to human TFPIalpha, increasing to 88 to 90% in the functional Kunitz-1 and Kunitz
      2 domains. Transfected primate cells expressing equivalent levels of GPI-linked
      pig or human TFPIalpha were assayed for binding of human factor Xa and inhibition
      of the human factor VIIa/tissue factor complex. The activity of the expressed pig
      anticoagulant was equivalent to that of the human protein in both measures of
      TFPI function in these systems. These data indicate that there are no apparent
      incompatibilities between recombinant pig TFPI and the human tissue factor
      pathway. Other factors must account for the thromboregulatory failure of pig
      endothelium and aberrant tissue factor activity in xenograft rejection.

PMID- 18611228
TI  - Lamellar corneal pig-to-rabbit xenotransplantation.

PMID- 18611229
TI  - Xenotransplantation literature update January-February, 2008.

PMID- 18611231
TI  - Re: Variations of the internal pudendal artery as a congenital contributing
      factor to age at onset of erectile dysfunction in Japanese.

PMID- 18611244
TI  - The aromatase inhibitor letrozole and inhibitors of insulin-like growth factor I
      receptor synergistically induce apoptosis in in vitro models of estrogen
      dependent breast cancer.
AB  - INTRODUCTION: Endocrine-dependent, estrogen receptor positive breast cancer cells
      proliferate in response to estrogens, synthesized by the cytochrome p450
      aromatase enzyme. Letrozole is a potent nonsteroidal aromatase inhibitor that is
      registered for the treatment of postmenopausal women with advanced metastatic
      breast cancers and in the neoadjuvant, early, and extended adjuvant indications.
      Because crosstalk exists between estrogen receptor and insulin-like growth factor
      I receptor (IGF-IR), the effect of combining a selective IGF-IR inhibitor (NVP
      AEW541) with letrozole was assessed in two independent in vitro models of
      estrogen-dependent breast cancer. METHODS: MCF7 and T47D cells stably expressing
      aromatase (MCF7/Aro and T47D/Aro) were used as in vitro models of aromatase
      driven breast cancer. The role of the IGF-IR pathway in breast cancer cells
      stimulated only by 17beta-estradiol or androstenedione was assessed by
      proliferation assays. The combination of letrozole and NVP-AEW541 was assessed
      for synergy in inhibiting cell proliferation using Chou-Talalay derived
      equations. Finally, combination or single agent effects on proliferation and
      apoptosis were assessed using proliferation assays, flow cytometry, and
      immunoblotting. RESULTS: Both MCF7 and T47D cells, as well as MCF7/Aro and
      T47D/Aro, exhibited sensitivity to inhibition of 17beta-estradiol dependent
      proliferation by NVP-AEW541. Letrozole combined with NVP-AEW541 synergistically
      inhibited androstenedione-dependent proliferation in aromatase-expressing cells
      with combination index values of 0.6 or less. Synergistic combination effects
      correlated with higher levels of apoptosis as compared with cells treated with
      the single agent alone. Treatment with either agent also appeared to inhibit IGF
      IR signalling via phosphoinositide 3-kinase. Notably, IGF-IR inhibition had
      limited effect on estrogen-dependent proliferation in the cell lines, but was
      clearly required for survival, suggesting that the combination of letrozole and
      IGF-IR inhibition sensitizes cells to apoptosis. CONCLUSION: Inhibition of the
      IGF-IR pathway and aromatase was synergistic in two independent estrogen
      dependent in vitro models of breast cancer. Moreover, synergism of NVP-AEW541 and
      letrozole correlated with induction of apoptosis, but not cell cycle arrest, in
      the cell lines tested. Combination of IGF-IR inhibitors and letrozole may hold
      promise for the treatment of patients with estrogen-dependent breast cancers.

PMID- 18611245
TI  - Quality of care for older adults with chronic obstructive pulmonary disease and
      asthma based on comparisons to practice guidelines and smoking status.
AB  - BACKGROUND: The purpose of this study was to describe the prevalence of
      respiratory diseases in older adults and compare the demographic, health and
      smoking characteristics of those with and without these diseases. Furthermore, we
      evaluate the association between smoking status and patterns in health care and
      how concordant this care is with guidelines. METHODS: Using a nationally
      representative sample of 29,902 older adults who participated in the Medicare
      Current Beneficiary Survey (1992-2002), we compared guideline recommendations on
      the treatment and prevention of chronic obstructive pulmonary disease and asthma
      with survey utilization data, including the use of bronchodilators, spirometry
      and influenza vaccine. RESULTS: 26% to 30% of older adults were diagnosed with or
      self-reported chronic respiratory diseases; however 69% received no
      pharmacological treatment and 30% of patients reporting use of pharmacological
      treatments did not receive short-acting bronchodilator inhalers. Current smokers
      appeared to receive significantly less care for respiratory diseases than non
      smokers or former smokers. CONCLUSION: Disparities between recommended and actual
      care for older adults with chronic lung disease require further research. The
      needs of older adults with co-morbidities and nicotine addiction deserve special
      attention in care as well as guideline development and implementation.

PMID- 18611246
TI  - Prevalence of antimicrobial resistance among bacterial pathogens isolated from
      cattle in different European countries: 2002-2004.
AB  - BACKGROUND: The project "Antibiotic resistance in bacteria of animal origin - II"
      (ARBAO-II) was funded by the European Union (FAIR5-QLK2-2002-01146) for the
      period 2003-2005, with the aim to establish a continuous monitoring of
      antimicrobial susceptibility among veterinary laboratories in European countries
      based on validated and harmonised methodologies. Available summary data of the
      susceptibility testing of the bacterial pathogens from the different laboratories
      were collected. METHOD: Antimicrobial susceptibility data for several bovine
      pathogens were obtained over a three year period (2002-2004). Each year the
      participating laboratories were requested to fill in excel-file templates with
      national summary data on the occurrence of antimicrobial resistance from
      different bacterial species.A proficiency test (EQAS - external quality assurance
      system) for antimicrobial susceptibility testing was conducted each year to test
      the accuracy of antimicrobial susceptibility testing in the participating
      laboratories. The data from this testing demonstrated that for the species
      included in the EQAS the results are comparable between countries. RESULTS: Data
      from 25,241 isolates were collected from 13 European countries. For
      Staphylococcus aureus from bovine mastitis major differences were apparent in the
      occurrence of resistance between countries and between the different
      antimicrobial agents tested. The highest frequency of resistance was observed for
      penicillin. For Mannheimia haemolytica resistance to ampicillin, tetracycline and
      trimethoprim/sulphonamide were observed in France, the Netherlands and Portugal.
      All isolates of Pasteurella multocida isolated in Finland and most of those from
      Denmark, England (and Wales), Italy and Sweden were susceptible to the majority
      of the antimicrobials. Streptococcus dysgalactiae and Streptococcus uberis
      isolates from Sweden were fully susceptible. For the other countries some
      resistance was observed to tetracycline, gentamicin and erythromycin. More
      resistance and variation of the resistance levels between countries were observed
      for Escherichia coli compared to the other bacterial species investigated.
      CONCLUSION: In general, isolates from Denmark, England (and Wales), the
      Netherlands, Norway, Sweden and Switzerland showed low frequencies of resistance,
      whereas many isolates from Belgium, France, Italy, Latvia and Spain were
      resistant to most antimicrobials tested. In the future, data on the prevalence of
      resistance should be used to develop guidelines for appropriate antimicrobial use
      in veterinary medicine.

PMID- 18611247
TI  - Gene disruption of the DNA topoisomerase IB small subunit induces a non-viable
      phenotype in the hemoflagellate Leishmania major.
AB  - BACKGROUND: The unusual heterodimeric leishmanial DNA topoisomerase IB consists
      of a large subunit containing the phylogenetically conserved "core" domain, and a
      small subunit harboring the C-terminal region with the characteristic tyrosine
      residue in the active site. RNAi silencing of any of both protomers induces a non
      viable phenotype in the hemoflagelate Trypanosoma brucei. Unfortunately, this
      approach is not suitable in Leishmania where gene replacement with an antibiotic
      marker is the only approach to generate lack-of-function mutants. In this work,
      we have successfully generated null mutants in the small subunit of the L. major
      DNA topoisomerase IB using two selection markers, each conferring resistance to
      hygromycin B and puromycin, respectively. RESULTS: We have successfully replaced
      both topS loci with two selection markers. However, to achieve the second
      transfection round, we have had to rescue the null-homozygous with an episomal
      vector carrying the Leishmania major topS gene. Phenotypic characterization of
      the L. major rescued strain and a L. major strain, which co-overexpresses both
      subunits, shows few differences in DNA relaxation and camptothecin cytotoxicity
      when it was compared to the wild-type strain. Studies on phosphatidylserine
      externalization show a poor incidence of camptothecin-induced programmed cell
      death in L. major, but an effective cell-cycle arrest occurs within the first 24
      h. S-Phase delay and G2/M reversible arrest was the main outcome at lower
      concentrations, but irreversible G2 arrest was detected at higher camptothecin
      pressure. CONCLUSION: Results obtained in this work evidence the essentiality of
      the topS gene encoding the L. major DNA topoisomerase IB small subunit.
      Reversibility of the camptothecin effect points to the existence of effective
      checkpoint mechanisms in Leishmania parasites.

PMID- 18611249
TI  - Ipsilateral free semitendinosus tendon graft transfer for reconstruction of
      chronic tears of the Achilles tendon.
AB  - BACKGROUND: Many techniques have been developed for the reconstruction of the
      Achilles tendon in chronic tears. In presence of a large gap (greater than 6
      centimetres), tendon augmentation is required. METHODS: We present our method of
      minimally invasive semitendinosus reconstruction for the Achilles tendon using
      one para-midline and one midline incision. RESULTS: The first incision is a 5 cm
      longitudinal incision, made 2 cm proximal and just medial to the palpable end of
      the residual tendon. The second incision is 3 cm long and is also longitudinal
      but is 2 cm distal and in the midline to the distal end of the tendon rupture.
      The distal and proximal Achilles tendon stumps are mobilised. After trying to
      reduce the gap of the ruptured Achilles tendon, if the gap produced is greater
      than 6 cm despite maximal plantar flexion of the ankle and traction on the
      Achilles tendon stumps, the ipsilateral semitendinosus tendon is harvested. The
      semitendinosus tendon is passed through small incisions in the substance of the
      proximal stump of the Achilles tendon, and it is sutured to the Achilles tendon.
      It is then passed beneath the intact skin bridge into the distal incision, and
      passed from medial to lateral through a transverse tenotomy in the distal stump.
      With the ankle in maximal plantar flexion, the semitendinosus tendon is sutured
      to the Achilles tendon at each entry and exit point CONCLUSION: This minimally
      invasive technique allows reconstruction of the Achilles tendon using the tendon
      of semitendinosus preserving skin integrity over the site most prone to wound
      breakdown, and can be especially used to reconstruct the Achilles tendon in the
      presence of large gap (greater than 6 centimetres).

PMID- 18611248
TI  - TGFbeta induces apoptosis and EMT in primary mouse hepatocytes independently of
      p53, p21Cip1 or Rb status.
AB  - BACKGROUND: TGFbeta has pleiotropic effects that range from regulation of
      proliferation and apoptosis to morphological changes and epithelial-mesenchymal
      transition (EMT). Some evidence suggests that these effects may be
      interconnected. We have recently reported that P53, P21Cip1 and pRB, three
      critical regulators of the G1/S transition are variably involved in TGFbeta
      induced cell cycle arrest in hepatocytes. As these proteins are also involved in
      the regulation of apoptosis in many circumstances, we investigated their
      contribution to other relevant TGFbeta-induced effects, namely apoptosis and EMT,
      and examined how the various processes were interrelated. METHODS: Primary mouse
      hepatocytes deficient in p53, p21 and/or Rb, singly or in combination were
      treated with TGFbeta for 24 to 96 hours. Apoptosis was quantified according to
      morphology and by immunostaining for cleaved-capsase 3. Epithelial and
      mesenchymal marker expression was studied using immunocytochemistry and real time
      PCR. RESULTS: We found that TGFbeta similarly induced morphological changes
      regardless of genotype and independently of proliferation index or sensitivity to
      inhibition of proliferation by TGFbeta. Morphological changes were accompanied by
      decrease in E-cadherin and increased Snail expression but the mesenchymal markers
      (N-cadherin, SMAalpha and Vimentin) studied remained unchanged. TGFbeta induced
      high levels of apoptosis in p53-/-, Rb-/-, p21cip1-/- and control hepatocytes
      although with slight differences in kinetics. This was unrelated to proliferation
      or changes in morphology and loss of cell-cell adhesion. However, hepatocytes
      deficient in both p53 and p21cip1were less sensitive to TGFbeta-induced
      apoptosis. CONCLUSION: Although p53, p21Cip1 and pRb are well known regulators of
      both proliferation and apoptosis in response to a multitude of stresses, we
      conclude that they are critical for TGFbeta-driven inhibition of hepatocytes
      proliferation, but only slightly modulate TGFbeta-induced apoptosis. This effect
      may depend on other parameters such as proliferation and the presence of other
      regulatory proteins as suggested by the consequences of p53, p21Cip1 double
      deficiency. Similarly, p53, p21Cip1 and pRB deficiency had no effect on the
      morphological changes and loss of cell adhesion which is thought to be critical
      for metastasis. This indicates that possible association of these genes with
      metastasis potential would be unlikely to involve TGFbeta-induced EMT.

PMID- 18611250
TI  - Measuring physiotherapy performance in patients with osteoarthritis of the knee:
      a prospective study.
AB  - BACKGROUND: Patients with knee osteoarthritis [OA] are commonly treated by
      physiotherapists in primary care. Measuring physiotherapy performance is
      important before developing strategies to improve quality. The purpose of this
      study was to measure physiotherapy performance in patients with knee OA by
      comparing clinical practice to evidence from systematic reviews. METHODS: We
      developed a data-collection form and invited all private practitioners in Norway
      [n = 2798] to prospectively collect data on the management of one patient with
      knee OA through 12 treatment session. Actual practice was compared to findings
      from an overview of systematic reviews summarising the effect of physiotherapy
      interventions for knee OA. RESULTS: A total of 297 physiotherapists reported
      their management for patients with knee OA. Exercise was the most common
      treatment used, provided by 98% of the physiotherapists. There is evidence of
      high quality that exercise reduces pain and improves function in patients with
      knee OA. Thirty-five percent of physiotherapists used acupuncture, low-level
      laser therapy or transcutaneous electrical nerve stimulation. There is evidence
      of moderate quality that these treatments reduce pain in knee OA. Patient
      education, supported by moderate quality evidence for improving psychological
      outcomes, was provided by 68%. Physiotherapists used a median of four different
      treatment modalities for each patient. They offered many treatment modalities
      based on evidence of low quality or without evidence from systematic reviews,
      e.g. traction and mobilisation, massage and stretching. CONCLUSION: Exercise was
      used in almost all treatment sessions in the management of knee OA. This practice
      is desirable since it is supported by high quality evidence. Physiotherapists
      also provide several other treatment modalities based on evidence of moderate or
      low quality, or no evidence from systematic reviews. Ways to promote high quality
      evidence into physiotherapy practice should be identified and evaluated.

PMID- 18611251
TI  - Vv-AMP1, a ripening induced peptide from Vitis vinifera shows strong antifungal
      activity.
AB  - BACKGROUND: Latest research shows that small antimicrobial peptides play a role
      in the innate defense system of plants. These peptides typically contribute to
      preformed defense by developing protective barriers around germinating seeds or
      between different tissue layers within plant organs. The encoding genes could
      also be upregulated by abiotic and biotic stimuli during active defense
      processes. The peptides display a broad spectrum of antimicrobial activities.
      Their potent anti-pathogenic characteristics have ensured that they are promising
      targets in the medical and agricultural biotechnology sectors. RESULTS: A berry
      specific cDNA sequence designated Vv-AMP1, Vitis vinifera antimicrobial peptide
      1, was isolated from Vitis vinifera. Vv-AMP1 encodes for a 77 amino acid peptide
      that shows sequence homology to the family of plant defensins. Vv-AMP1 is
      expressed in a tissue specific, developmentally regulated manner, being only
      expressed in berry tissue at the onset of berry ripening and onwards. Treatment
      of leaf and berry tissue with biotic or abiotic factors did not lead to increased
      expression of Vv-AMP1 under the conditions tested. The predicted signal peptide
      of Vv-AMP1, fused to the green fluorescent protein (GFP), showed that the signal
      peptide allowed accumulation of its product in the apoplast. Vv-AMP1 peptide,
      produced in Escherichia coli, had a molecular mass of 5.495 kDa as determined by
      mass spectrometry. Recombinant Vv-AMP1 was extremely heat-stable and showed
      strong antifungal activity against a broad spectrum of plant pathogenic fungi,
      with very high levels of activity against the wilting disease causing pathogens
      Fusarium oxysporum and Verticillium dahliae. The Vv-AMP1 peptide did not induce
      morphological changes on the treated fungal hyphae, but instead strongly
      inhibited hyphal elongation. A propidium iodide uptake assay suggested that the
      inhibitory activity of Vv-AMP1 might be associated with altering the membrane
      permeability of the fungal membranes. CONCLUSION: A berry specific cDNA clone, Vv
      AMP1, was isolated and characterized and shown to encode a plant defensin.
      Recombinant Vv-AMP1 displayed non-morphogenic antifungal activity against a broad
      spectrum of fungi, probably altering the membrane permeability of the fungal
      pathogens. The expression of this peptide is highly regulated in Vitis vinifera,
      hinting at an important defense role during berry-ripening.

PMID- 18611252
TI  - Analysis of heterogeneity and epistasis in physiological mixed populations by
      combined structural equation modelling and latent class analysis.
AB  - BACKGROUND: Biological systems are interacting, molecular networks in which
      genetic variation contributes to phenotypic heterogeneity. This heterogeneity is
      traditionally modelled as a dichotomous trait (e.g. affected vs. non-affected).
      This is far too simplistic considering the complexity and genetic variations of
      such networks. METHODS: In this study on type 2 diabetes mellitus, heterogeneity
      was resolved in a latent class framework combined with structural equation
      modelling using phenotypic indicators of distinct physiological processes. We
      modelled the clinical condition "the metabolic syndrome", which is known to be a
      heterogeneous and polygenic condition with a clinical endpoint (type 2 diabetes
      mellitus). In the model presented here, genetic factors were not included and no
      genetic model is assumed except that genes operate in networks. The impact of
      stratification of the study population on genetic interaction was demonstrated by
      analysis of several genes previously associated with the metabolic syndrome and
      type 2 diabetes mellitus. RESULTS: The analysis revealed the existence of 19
      distinct subpopulations with a different propensity to develop diabetes mellitus
      within a large healthy study population. The allocation of subjects into
      subpopulations was highly accurate with an entropy measure of nearly 0.9.
      Although very few gene variants were directly associated with metabolic syndrome
      in the total study sample, almost one third of all possible epistatic
      interactions were highly significant. In particular, the number of interactions
      increased after stratifying the study population, suggesting that interactions
      are masked in heterogenous populations. In addition, the genetic variance
      increased by an average of 35-fold when analysed in the subpopulations.
      CONCLUSION: The major conclusions from this study are that the likelihood of
      detecting true association between genetic variants and complex traits increases
      tremendously when studied in physiological homogenous subpopulations and on
      inclusion of epistasis in the analysis, whereas epistasis (i.e. genetic networks)
      is ubiquitous and should be the basis in modelling any biological process.

PMID- 18611253
TI  - Understanding the explanatory model of the patient on their medically unexplained
      symptoms and its implication on treatment development research: a Sri Lanka
      Study.
AB  - BACKGROUND: Patients with medically unexplained symptoms (MUS) are often
      distressed, disabled and dissatisfied with the care they receive. Illness beliefs
      held by patients have a major influence on the decision to consult, persistence
      of symptoms and the degree of disability. Illness perception models consist of
      frameworks to organise information from multiple sources into distinct but
      interrelated dimensions: identity (the illness label), cause, consequences,
      emotional representations perceived control and timeline. Our aim was to elicit
      the illness perceptions of patients with MUS in Sri Lankan primary care to modify
      and improve a CBT intervention. METHOD: An intervention study was conducted in a
      hospital primary care clinic in Colombo, Sri Lanka using CBT for MUS. As a part
      of the baseline assessment, qualitative data was collected using; the Short
      Explanatory Model Interview (SEMI), from 68 patients (16-65 years) with MUS. We
      categorised the qualitative data in to key components of the illness perception
      model, to refine CBT intervention for a subsequent larger trial study. RESULTS:
      The cohort was chronically ill and 87% of the patients were ill for more than six
      months (range six months to 20 years) with 5 or more symptoms and 6 or more
      visits over preceding six months. A majority were unable to offer an explanation
      on identity (59%) or the cause (56%), but in the consequence domain 95% expressed
      significant illness worries; 37% believed their symptoms indicated moderately
      serious illness and 58% very serious illness. Reflecting emotional
      representation, 33% reported fear of death, 20% fear of paralysis, 13% fear of
      developing cancer and the rest unspecified incurable illness. Consequence and
      emotional domains were significant determinants of distress and consultations.
      Their repeated visits were to seek help to alleviate symptoms. Only a minority
      expected investigations (8.8 %) or diagnosis (8.8%). However, the doctors who had
      previously treated them allegedly concentrated more on identity than cause. The
      above information was used to develop simple techniques incorporating analogies
      to alter their perceptions CONCLUSION: The illness perception model is useful in
      understanding the continued distress of patients with persistent symptoms without
      an underlying organic cause. Hence it can make a significant contribution when
      developing and evaluating culturally sensitive patient friendly interventions.

PMID- 18611254
TI  - Routine evaluation of left ventricular diastolic function by cardiovascular
      magnetic resonance: a practical approach.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) has excellent capabilities to
      assess ventricular systolic function. Current clinical scenarios warrant routine
      evaluation of ventricular diastolic function for complete evaluation, especially
      in congestive heart failure patients. To our knowledge, no systematic assessment
      of diastolic function over a range of lusitropy has been performed using CMR.
      METHODS AND RESULTS: Left ventricular diastolic function was assessed in 31
      subjects (10 controls) who underwent CMR and compared with Transthoracic
      echocardiogram (TTE) evaluation of mitral valve (MV) and pulmonary vein (PV)
      blood flow. Blood flow in the MV and PV were successfully imaged by CMR for all
      cases (31/31,100%) while TTE evaluated flow in all MV (31/31,100%) but only 21/31
      PV (68%) cases. Velocities of MV flow (E and A) measured by CMR correlated well
      with TTE (r = 0.81, p < 0.001), but demonstrated a systematic underestimation by
      CMR compared to TTE (slope = 0.77). Bland-Altman analysis of the E:A ratio and
      deceleration time (DT) calculated from each modality showed excellent agreement
      (bias -0.29, and -10.3 ms for E:A and DT, respectively). When assessing
      morphology using TTE, CMR correctly identified patients as having normal or
      abnormal inflow conditions. CONCLUSION: We have shown that there is homology
      between CMR and TTE for the assessment of diastolic inflow over a wide range of
      conditions, including normal, impaired relaxation and restrictive. There is
      excellent agreement of quantitative velocity measurements between CMR and TTE.
      Diastolic blood flow assessment by CMR can be performed in a single scan, with
      times ranging from 20 sec to 3 min, and we show that there is good indication for
      applying CMR to assess diastolic conditions, either as an adjunctive test when
      evaluating systolic function, or even as a primary test when TTE data cannot be
      obtained.

PMID- 18611255
TI  - Knowledge and attitudes of primary care physicians in the management of patients
      at risk for cardiovascular events.
AB  - BACKGROUND: Adherence to clinical practice guidelines for management of
      cardiovascular disease (CVD) is suboptimal. The purposes of this study were to
      identify practice patterns and barriers among U.S. general internists and family
      physicians in regard to cardiovascular risk management, and examine the
      association between physician characteristics and cardiovascular risk management.
      METHODS: A case vignette survey focused on cardiovascular disease risk management
      was distributed to a random sample of 12,000 U.S. family physicians and general
      internists between November and December 2006. RESULTS: Responses from a total of
      888 practicing primary care physicians who see 60 patients per week were used for
      analysis. In an asymptomatic patient at low risk for cardiovascular event, 28% of
      family physicians and 37% of general internists made guideline-based preventive
      choices for no antiplatelet therapy (p < .01). In a patient at high risk for
      cardiovascular event, 59% of family physicians and 56% of general internists
      identified the guideline-based goal for serum fasting LDL level (< 100 mg/dl).
      Guideline adherence was inversely related to years in practice and volume of
      patients seen. Cost of medications (87.7%), adherence to medications (74.1%),
      adequate time for counseling (55.7%), patient education tools (47.1%), knowledge
      and skills to recommend dietary changes (47.8%) and facilitate patient adherence
      (52.0%) were cited as significant barriers to CVD risk management. CONCLUSION:
      Despite the benefits demonstrated for managing cardiovascular risks, gaps remain
      in primary care practitioners' management of risks according to guideline
      recommendations. Innovative educational approaches that address barriers may
      facilitate the implementation of guideline-based recommendations in CVD risk
      management.

PMID- 18611256
TI  - Abetalipoproteinemia: two case reports and literature review.
AB  - Abetalipoproteinemia (ABL, OMIM 200100) is a rare, autosomal recessive disorder,
      characterized by fat malabsorption, acanthocytosis and hypocholesterolemia in
      infancy. Later in life, deficiency of fat-soluble vitamins is associated with
      development of atypical retinitis pigmentosa, coagulopathy, posterior column
      neuropathy and myopathy. ABL results from mutations in the gene encoding the
      large subunit of microsomal triglyceride transfer protein (MTP; OMIM 157147). To
      date at least 33 MTP mutations have been identified in 43 ABL patients. We
      describe the clinical progress of two patients, both currently in the fifth
      decade of life, who were diagnosed with ABL as children and were treated with
      high oral doses of fat soluble vitamins, including vitamin E over the last three
      decades. Treatment appears to have been associated with arrest of the neuropathy
      and other complications in both patients. Because pharmacologic inhibition of MTP
      is being developed as a novel approach to reduce plasma cholesterol for
      prevention of cardiovascular disease, defining the long-term clinical features of
      patients with a natural deficiency in MTP might provide some insight into the
      possible effects of such treatments. We review the range of clinical, biochemical
      and molecular perturbations in ABL.

PMID- 18611257
TI  - Mouse T-cells restrict replication of human immunodeficiency virus at the level
      of integration.
AB  - BACKGROUND: The development of an immunocompetent, genetically modified mouse
      model to study HIV-1 pathogenesis and to test antiviral strategies has been
      hampered by the fact that cells from native mice do not or only inefficiently
      support several steps of the HIV-1 replication cycle. Upon HIV-1 infection, mouse
      T-cell lines fail to express viral proteins, but the underlying replication
      barrier has thus far not been unambiguously identified. Here, we performed a
      kinetic and quantitative assessment of consecutive steps in the early phase of
      the HIV-1 replication cycle in T-cells from mice and humans. RESULTS: Both T-cell
      lines and primary T-cells from mice harbor a severe post-entry defect that is
      independent of potential species-specTR transactivation. Reverse transcription
      occurred efficiently following VSV-G-mediated entry of virions into mouse T
      cells, and abundant levels of 2-LTR circles indicated successful nuclear import
      of the pre-integration complex. To probe the next step in the retroviral
      replication cycle, i.e. the integration of HIV-1 into the host cell genome, we
      established and validated a nested real-time PCR to specifically quantify HIV-1
      integrants exploiting highly repetitive mouse B1 elements. Importantly, we
      demonstrate that the frequency of integrant formation is diminished 18- to > 305
      fold in mouse T-cell lines compared to a human counterpart, resulting in a
      largely abortive infection. Moreover, differences in transgene expression from
      residual vector integrants, the transcription off which is cyclin T1-independent,
      provided evidence for an additional, peri-integrational deficit in certain mouse
      T-cell lines. CONCLUSION: In contrast to earlier reports, we find that mouse T
      cells efficiently support early replication steps up to and including nuclear
      import, but restrict HIV-1 at the level of chromosomal integration.

PMID- 18611258
TI  - Population-based estimate of sibling risk for preterm birth, preterm premature
      rupture of membranes, placental abruption and pre-eclampsia.
AB  - BACKGROUND: Adverse pregnancy outcomes, such as preterm birth, preeclampsia and
      placental abruption, are common, with acute and long-term complications for both
      the mother and infant. Etiologies underlying such adverse outcomes are not well
      understood. As maternal and fetal genetic factors may influence these outcomes,
      we estimated the magnitude of familial aggregation as one index of possible
      heritable contributions. Using the Missouri Department of Health's maternally
      linked birth certificate database, we performed a retrospective population-based
      cohort study of births (1989-1997), designating an individual born from an
      affected pregnancy as the proband for each outcome studied. We estimated the
      increased risk to siblings compared to the population risk, using the sibling
      risk ratio, lambdas, and sibling-sibling odds ratio (sib-sib OR), for the adverse
      pregnancy outcomes of preterm birth, preterm premature rupture of membranes
      (PPROM), placental abruption, and pre-eclampsia. RESULTS: Risk to siblings of an
      affected individual was elevated above the population prevalence of a given
      disorder, as indicated by lambdaS (lambdaS (95% CI): 4.3 (4.0-4.6), 8.2 (6.5
      9.9), 4.0 (2.6-5.3), and 4.5 (4.4-4.8), for preterm birth, PPROM, placental
      abruption, and pre-eclampsia, respectively). Risk to siblings of an affected
      individual was similarly elevated above that of siblings of unaffected
      individuals, as indicated by the sib-sib OR (sib-sib OR adjusted for known risk
      factors (95% CI): 4.2 (3.9-4.5), 9.6 (7.6-12.2), 3.8 (2.6-5.5), 8.1 (7.5-8.8) for
      preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively).
      CONCLUSION: These results suggest that the adverse pregnancy outcomes of preterm
      birth, PPROM, placental abruption, and pre-eclampsia aggregate in families, which
      may be explained in part by genetics.

PMID- 18611259
TI  - Metabolic modelling of polyhydroxyalkanoate copolymers production by mixed
      microbial cultures.
AB  - BACKGROUND: This paper presents a metabolic model describing the production of
      polyhydroxyalkanoate (PHA) copolymers in mixed microbial cultures, using mixtures
      of acetic and propionic acid as carbon source material. Material and energetic
      balances were established on the basis of previously elucidated metabolic
      pathways. Equations were derived for the theoretical yields for cell growth and
      PHA production on mixtures of acetic and propionic acid as functions of the
      oxidative phosphorylation efficiency, P/O ratio. The oxidative phosphorylation
      efficiency was estimated from rate measurements, which in turn allowed the
      estimation of the theoretical yield coefficients. RESULTS: The model was
      validated with experimental data collected in a sequencing batch reactor (SBR)
      operated under varying feeding conditions: feeding of acetic and propionic acid
      separately (control experiments), and the feeding of acetic and propionic acid
      simultaneously. Two different feast and famine culture enrichment strategies were
      studied: (i) either with acetate or (ii) with propionate as carbon source
      material. Metabolic flux analysis (MFA) was performed for the different feeding
      conditions and culture enrichment strategies. Flux balance analysis (FBA) was
      used to calculate optimal feeding scenarios for high quality PHA polymers
      production, where it was found that a suitable polymer would be obtained when
      acetate is fed in excess and the feeding rate of propionate is limited to
      approximately 0.17 C-mol/(C-mol.h). The results were compared with published pure
      culture metabolic studies. CONCLUSION: Acetate was more conducive toward the
      enrichment of a microbial culture with higher PHA storage fluxes and yields as
      compared to propionate. The P/O ratio was not only influenced by the selected
      microbial culture, but also by the carbon substrate fed to each culture, where
      higher P/O ratio values were consistently observed for acetate than propionate.
      MFA studies suggest that when mixtures of acetate and propionate are fed to the
      cultures, the catabolic activity is primarily guaranteed through acetate uptake,
      and the characteristic P/O ratio of acetate prevails over that of propionate.
      This study suggests that the PHA production process by mixed microbial cultures
      has the potential to be comparable or even more favourable than pure cultures.

PMID- 18611260
TI  - Burrowing of urinary bladder wall by the tip of a size 22 Fr silicone foley
      catheter in an adult male patient with multiple sclerosis and suprapubic
      cystostomy: should caution be exercised in using a size 22 Fr silicone foley
      catheter for long-term drainage of neuropathic bladder?
AB  - INTRODUCTION: Silicone Foley catheters tend to become stiffer as size of the
      catheter increases. Whereas the tip of a size 12 French silicone, Foley catheter
      is soft and flexible, a size 24 French silicone, Foley catheter is distinctly
      stiff. Chronically inflamed neuropathic bladders are susceptible to perforation
      by the tip of a Foley catheter. We report a patient with multiple sclerosis and
      moderately severe chronic cystitis, in whom a size 22 French Foley catheter
      burrowed through the dome of urinary bladder. CASE PRESENTATION: A 55-year-old,
      Caucasian male suffering from multiple sclerosis underwent suprapubic cystostomy
      in January 2007. Initially, a size 16 Fr. silicone, Foley, catheter was inserted.
      During subsequent catheter changes, silicone Foley catheters of progressively
      increasing sizes were inserted and in July 2007, a size 22 Fr. catheter was used
      in order to prevent blockages and consequent bypassing of urine. In April 2008,
      he had an uneventful change of suprapubic catheter; but a week later, this
      patient developed profuse bypassing. On examination, suprapubic catheter
      contained fresh blood; there was hardly any urine in the leg bag, which was
      attached to suprapubic catheter. Cystogram showed localised extravasation of
      contrast on the superior aspect of urinary bladder around the tip of Foley
      catheter, which protruded beyond the dome of urinary bladder. The size 22 Fr.
      catheter was removed and a size 20 Fr silicone, Foley, catheter was inserted
      ensuring that the tip of catheter pointed towards bladder neck. This patient
      received gentamicin intravenously and he was prescribed ciprofloxacin for five
      days. He did not develop temperature or other features of sepsis. Bypassing
      stopped completely. CONCLUSION: In this patient, bladder biopsy had shown
      moderately severe chronic inflammation and congestion. We learn from this case
      that we should have used a smaller size catheter, which has a softer texture and
      changed the catheter at shorter intervals rather than insert a larger bore
      catheter, and run the risk of perforation of neuropathic bladder by the tip of a
      stiff Foley catheter.

PMID- 18611261
TI  - Different serological cross-reactivity of Trypanosoma rangeli forms in
      Trypanosoma cruzi-infected patients sera.
AB  - BACKGROUND: American Trypanosomiasis or Chagas disease is caused by Trypanosoma
      cruzi which currently infects approximately 16 million people in the Americas
      causing high morbidity and mortality. Diagnosis of American trypanosomiasis
      relies on serology, primarily using indirect immunofluorescence assay (IFA) with
      T. cruzi epimastigote forms. The closely related but nonpathogenic Trypanosoma
      rangeli has a sympatric distribution with T. cruzi and is carried by the same
      vectors. As a result false positives are frequently generated. This confounding
      factor leads to increased diagnostic test costs and where false positives are not
      caught, endangers human health due to the toxicity of the drugs used to treat
      Chagas disease. RESULTS: In the present study, serologic cross-reactivity between
      the two species was compared for the currently used epimastigote form and the
      more pathologically relevant trypomastigote form, using IFA and immunoblotting
      (IB) assays. Our results reveal an important decrease in cross reactivity when T.
      rangeli culture-derived trypomastigotes are used in IFA based diagnosis of Chagas
      disease. Western blot results using sera from both acute and chronic chagasic
      patients presenting with cardiac, indeterminate or digestive disease revealed
      similar, but not identical, antigenic profiles. CONCLUSION: This is the first
      study addressing the serological cross-reactivity between distinct forms and
      strains of T. rangeli and T. cruzi using sera from distinct phases of the
      Chagasic infection. Several T. rangeli-specific proteins were detected, which may
      have potential as diagnostic tools.

PMID- 18611262
TI  - Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1,
      IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II.
AB  - INTRODUCTION: Obesity has consistently been associated with postmenopausal breast
      cancer risk. Proteins that are secreted by adipose tissue or are involved in
      regulating body mass may play a role in breast tumor development. METHODS: We
      conducted a nested case-control study among postmenopausal women from the
      American Cancer Society Cancer Prevention Study II Nutrition Cohort to determine
      whether genes associated with obesity increase risk for breast cancer. Tagging
      single nucleotide polymorphisms (SNPs) were selected to capture common variation
      across seven candidate genes that encode adipose-related proteins: ADRB2, ADRB3,
      GHRL, HSD11B1, IRS1, IRS2, and SHC1. Thirty-nine SNPs were genotyped in 648 cases
      and 659 controls. Logistic regression models were used to examine the association
      between each tagging SNP and risk for breast cancer while adjusting for matching
      factors and potential confounders. We also examined whether these SNPs were
      associated with measures of adult adiposity. RESULTS: Two out of five tagging
      SNPs in HSD11B1 were associated with breast cancer (rs11807619, P = 0.006;
      rs932335, P = 0.0001). rs11807619 and rs932335 were highly correlated (r2 = 0.74)
      and, when modeled as a haplotype, only haplotypes containing the rs932335 C
      allele were associated with breast cancer. The rs932335 C allele was associated
      with a nearly twofold increased risk for breast cancer (odds ratio = 1.83, 95%
      confidence interval = 1.01-3.33 for C/C versus G/G). Three of the 11 SNPs for
      IRS2 were associated with breast cancer (rs4773082, P = 0.007; rs2289046, P =
      0.016; rs754204, P = 0.03). When these three SNPs were examined as a haplotype,
      only the haplotype that included the G allele of rs2289046 was associated with
      breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63-0.92 for TGC
      versus CAT). IRS2 rs2289046, rs754204, and rs12584136 were also associated with
      adult weight gain but only among cases. None of the other SNPs in any gene
      investigated were associated with breast cancer or adiposity. CONCLUSION: Our
      findings suggest that these tagging SNPs in HSD11B1 and IRS2 mark regions of the
      genome that may harbor risk alleles for breast cancer, and these associations are
      probably independent of adiposity.

PMID- 18611263
TI  - Social inequalities in self-rated health by age: cross-sectional study of 22,457
      middle-aged men and women.
AB  - BACKGROUND: We investigate the association between occupational social class and
      self-rated health (SRH) at different ages in men and women. METHODS: Cross
      sectional population study of 22,457 men and women aged 39-79 years living in the
      general community in Norfolk, United Kingdom, recruited using general practice
      age-sex registers in 1993-1997. The relationship between self-rated health and
      social class was examined using logistic regression, with a poor or moderate
      rating as the outcome. RESULTS: The prevalence of poor or moderate (lower) self
      rated health increased with increasing age in both men and women. There was a
      strong social class gradient: in manual classes, men and women under 50 years of
      age had a prevalence of lower self-rated health similar to that seen in men and
      women in non-manual social classes over 70 years old. Even after adjustment for
      age, educational status, and lifestyle factors (body mass index (BMI), smoking,
      physical activity and alcohol consumption) there was still strong evidence of a
      social gradient in self-rated health, with unskilled men and women approximately
      twice as likely to report lower self-rated health as professionals (OR(men) =
      2.44 (95%CI 1.69, 3.50); OR(women) = 1.97 (95%CI 1.45, 2.68). CONCLUSION: There
      was a strong gradient of decreased SRH with age in both men and women. We found a
      strong cross-sectional association between SRH and social class, which was
      independent of education and major health related behaviors. The social class
      differential in SRH was similar with age. Prospective studies to confirm this
      association should explore social and emotional as well as physical pathways to
      inequalities in self reported health.

PMID- 18611264
TI  - Analysis of gene expression in a developmental context emphasizes distinct
      biological leitmotifs in human cancers.
AB  - BACKGROUND: In recent years, the molecular underpinnings of the long-observed
      resemblance between neoplastic and immature tissue have begun to emerge. Genome
      wide transcriptional profiling has revealed similar gene expression signatures in
      several tumor types and early developmental stages of their tissue of origin.
      However, it remains unclear whether such a relationship is a universal feature of
      malignancy, whether heterogeneities exist in the developmental component of
      different tumor types and to which degree the resemblance between cancer and
      development is a tissue-specific phenomenon. RESULTS: We defined a developmental
      landscape by summarizing the main features of ten developmental time courses and
      projected gene expression from a variety of human tumor types onto this
      landscape. This comparison demonstrates a clear imprint of developmental gene
      expression in a wide range of tumors and with respect to different, even non
      cognate developmental backgrounds. Our analysis reveals three classes of cancers
      with developmentally distinct transcriptional patterns. We characterize the
      biological processes dominating these classes and validate the class distinction
      with respect to a new time series of murine embryonic lung development. Finally,
      we identify a set of genes that are upregulated in most cancers and we show that
      this signature is active in early development. CONCLUSION: This systematic and
      quantitative overview of the relationship between the neoplastic and
      developmental transcriptome spanning dozens of tissues provides a reliable
      outline of global trends in cancer gene expression, reveals potentially
      clinically relevant differences in the gene expression of different cancer types
      and represents a reference framework for interpretation of smaller-scale
      functional studies.

PMID- 18611265
TI  - A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer:
      data from the European Randomized Study of Prostate Cancer Screening in Goteborg,
      Sweden.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is widely used to detect prostate
      cancer. The low positive predictive value of elevated PSA results in large
      numbers of unnecessary prostate biopsies. We set out to determine whether a
      multivariable model including four kallikrein forms (total, free, and intact PSA,
      and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously
      unscreened men with elevated total PSA. METHODS: The study cohort comprised 740
      men in Goteborg, Sweden, undergoing biopsy during the first round of the European
      Randomized study of Screening for Prostate Cancer. We calculated the area-under
      the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model
      including age and PSA (the 'laboratory' model) and age, PSA and digital rectal
      exam (the 'clinical' model) were compared with those for models that also
      included additional kallikreins. RESULTS: Addition of free and intact PSA and hK2
      improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and
      clinical models respectively. Using a 20% risk of prostate cancer as the
      threshold for biopsy would have reduced the number of biopsies by 424 (57%) and
      missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers.
      CONCLUSION: Multiple kallikrein forms measured in blood can predict the result of
      biopsy in previously unscreened men with elevated PSA. A multivariable model can
      determine which men should be advised to undergo biopsy and which might be
      advised to continue screening, but defer biopsy until there was stronger evidence
      of malignancy.

PMID- 18611266
TI  - Wndchrm - an open source utility for biological image analysis.
AB  - BACKGROUND: Biological imaging is an emerging field, covering a wide range of
      applications in biological and clinical research. However, while machinery for
      automated experimenting and data acquisition has been developing rapidly in the
      past years, automated image analysis often introduces a bottleneck in high
      content screening. METHODS: Wndchrm is an open source utility for biological
      image analysis. The software works by first extracting image content descriptors
      from the raw image, image transforms, and compound image transforms. Then, the
      most informative features are selected, and the feature vector of each image is
      used for classification and similarity measurement. RESULTS: Wndchrm has been
      tested using several publicly available biological datasets, and provided results
      which are favorably comparable to the performance of task-specific algorithms
      developed for these datasets. The simple user interface allows researchers who
      are not knowledgeable in computer vision methods and have no background in
      computer programming to apply image analysis to their data. CONCLUSION: We
      suggest that wndchrm can be effectively used for a wide range of biological image
      analysis tasks. Using wndchrm can allow scientists to perform automated
      biological image analysis while avoiding the costly challenge of implementing
      computer vision and pattern recognition algorithms.

PMID- 18611267
TI  - Concerted gene recruitment in early plant evolution.
AB  - BACKGROUND: Horizontal gene transfer occurs frequently in prokaryotes and
      unicellular eukaryotes. Anciently acquired genes, if retained among descendants,
      might significantly affect the long-term evolution of the recipient lineage.
      However, no systematic studies on the scope of anciently acquired genes and their
      impact on macroevolution are currently available in eukaryotes. RESULTS: Analyses
      of the genome of the red alga Cyanidioschyzon identified 37 genes that were
      acquired from non-organellar sources prior to the split of red algae and green
      plants. Ten of these genes are rarely found in cyanobacteria or have additional
      plastid-derived homologs in plants. These genes most likely provided new
      functions, often essential for plant growth and development, to the ancestral
      plant. Many remaining genes may represent replacements of endogenous homologs
      with a similar function. Furthermore, over 78% of the anciently acquired genes
      are related to the biogenesis and functionality of plastids, the defining
      character of plants. CONCLUSION: Our data suggest that, although ancient
      horizontal gene transfer events did occur in eukaryotic evolution, the number of
      acquired genes does not predict the role of horizontal gene transfer in the
      adaptation of the recipient organism. Our data also show that multiple
      independently acquired genes are able to generate and optimize key evolutionary
      novelties in major eukaryotic groups. In light of these findings, we propose and
      discuss a general mechanism of horizontal gene transfer in the macroevolution of
      eukaryotes.

PMID- 18611268
TI  - A community resource for high-throughput quantitative RT-PCR analysis of
      transcription factor gene expression in Medicago truncatula.
AB  - BACKGROUND: Medicago truncatula is a model legume species that is currently the
      focus of an international genome sequencing effort. Although several different
      oligonucleotide and cDNA arrays have been produced for genome-wide transcript
      analysis of this species, intrinsic limitations in the sensitivity of
      hybridization-based technologies mean that transcripts of genes expressed at low
      levels cannot be measured accurately with these tools. Amongst such genes are
      many encoding transcription factors (TFs), which are arguably the most important
      class of regulatory proteins. Quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR) is the most sensitive method currently available for
      transcript quantification, and one that can be scaled up to analyze transcripts
      of thousands of genes in parallel. Thus, qRT-PCR is an ideal method to tackle the
      problem of TF transcript quantification in Medicago and other plants. RESULTS: We
      established a bioinformatics pipeline to identify putative TF genes in Medicago
      truncatula and to design gene-specific oligonucleotide primers for qRT-PCR
      analysis of TF transcripts. We validated the efficacy and gene-specificity of
      over 1000 TF primer pairs and utilized these to identify sets of organ-enhanced
      TF genes that may play important roles in organ development or differentiation in
      this species. This community resource will be developed further as more genome
      sequence becomes available, with the ultimate goal of producing validated, gene
      specific primers for all Medicago TF genes. CONCLUSION: High-throughput qRT-PCR
      using a 384-well plate format enables rapid, flexible, and sensitive
      quantification of all predicted Medicago transcription factor mRNAs. This
      resource has been utilized recently by several groups in Europe, Australia, and
      the USA, and we expect that it will become the 'gold-standard' for TF transcript
      profiling in Medicago truncatula.

PMID- 18611269
TI  - Topoisomerase II inhibition involves characteristic chromosomal expression
      patterns.
AB  - BACKGROUND: The phenomenon of co-localization of transcriptionally upregulated
      genes showing similar expression levels is known across all eukaryotic genomes.
      We recently mapped the Aroclor 1254-regulated transcriptome back onto the genome
      and provided evidence for the statistically significant co-localization of
      regulated genes. They did, however, not always show similar expression levels,
      and many of the regulated genes were, in fact, repressed. RESULTS: In this study,
      we were able to reproduce this observation with microarray data stemming from 1)
      human hepatocytes treated with the gyrase and potential topoisomerase II
      inhibitor trovafloxacin, 2) human hepatocytes treated with the topoisomerase II
      inhibitor doxorubicin and 3) mouse lymphoma cells treated with the topoisomerase
      II inhibitor etoposide. We found statistically significant co-localization of
      regulated gene pairs--induced and repressed--within the window size of 0-100 kbp.
      Notably, by using microarray data stemming from lung tissue of a mouse transgenic
      line overexpressing the transcription factor c-myc, which served as a negative
      control, we found regulated genes to be located with regard to each other nearly
      in the same way as genes distributed randomly all over the genome (0-100 kbp).
      CONCLUSION: We suggest topoisomerase II inhibition by Aroclor 1254,
      trovafloxacin, doxorubicin, and etoposide to be responsible for significant co
      localization of regulated genes through the inability of the stabilized enzyme
      complexes to religate DNA. Within the permanently opened chromatin domains,
      neighbored genes might be allowed to be regulated. Overexpression of c-myc,
      however, does not inhibit topoisomerase II activity. Consequently, the enzyme is
      able to perform its normal function of transiently breaking and rejoining the DNA
      double strand. As a result, exclusively target genes are regulated.

PMID- 18611270
TI  - High density linkage disequilibrium maps of chromosome 14 in Holstein and Angus
      cattle.
AB  - BACKGROUND: Linkage disequilibrium (LD) maps can provide a wealth of information
      on specific marker-phenotype relationships, especially in areas of the genome
      where positional candidate genes with similar functions are located. A recently
      published high resolution radiation hybrid map of bovine chromosome 14 (BTA14)
      together with the bovine physical map have enabled the creation of more accurate
      LD maps for BTA14 in both dairy and beef cattle. RESULTS: Over 500 Single
      Nucleotide Polymorphism (SNP) markers from both Angus and Holstein animals had
      their phased haplotypes estimated using GENOPROB and their pairwise r2 values
      compared. For both breeds, results showed that average LD extends at moderate
      levels up to 100 kilo base pairs (kbp) and falls to background levels after 500
      kbp. Haplotype block structure analysis using HAPLOVIEW under the four gamete
      rule identified 122 haplotype blocks for both Angus and Holstein. In addition,
      SNP tagging analysis identified 410 SNPs and 420 SNPs in Holstein and Angus,
      respectively, for future whole genome association studies on BTA14. Correlation
      analysis for marker pairs common to these two breeds confirmed that there are no
      substantial correlations between r-values at distances over 10 kbp. Comparison of
      extended haplotype homozygosity (EHH), which calculates the LD decay away from a
      core haplotype, shows that in Holstein there is long range LD decay away from the
      DGAT1 region consistent with the selection for milk fat % in this population.
      Comparison of EHH values for Angus in the same region shows very little long
      range LD. CONCLUSION: Overall, the results presented here can be applied in
      future single or haplotype association analysis for both populations, aiding in
      confirming or excluding potential polymorphisms as causative mutations,
      especially around Quantitative Trait Loci regions. In addition, knowledge of
      specific LD information among markers will aid the research community in
      selecting appropriate markers for whole genome association studies.

PMID- 18611271
TI  - Impact of intermittent preventive treatment with sulphadoxine-pyrimethamine
      targeting the transmission season on the incidence of clinical malaria in
      children in Mali.
AB  - BACKGROUND: Recent studies have shown that intermittent preventive malaria
      treatment (IPT) in infants in areas of stable malaria transmission reduces
      malaria and severe anaemia incidence. However in most areas malaria morbidity and
      mortality remain high in older children. METHODS: To evaluate the effect of
      seasonal IPT with sulphadoxine pyrimethamine (SP) on incidence of malaria disease
      in area of seasonal transmission, 262 children 6 months-10 years in Kambila, Mali
      were randomized to receive either IPT with SP twice at eight weeks interval or no
      IPT during the transmission season of 2002 and were followed up for 12 months.
      Subjects were also followed during the subsequent transmission season in 2003 to
      assess possible rebound effect. Clinical malaria cases were treated with SP and
      followed to assess the in vivo response during both periods. RESULTS: The
      incidence rate of malaria disease per 1,000 person-months during the first 12
      months was 3.2 episodes in the treatment group vs. 5.8 episodes in the control
      group with age-adjusted Protective Efficacy (PE) of 42.5%; [95% CI 28.6%-53.8%].
      When the first 16 weeks of follow up is considered age-adjusted PE was 67.5% [95%
      CI 55.3% - 76.6%]. During the subsequent transmission season, the incidence of
      clinical malaria per 1000 persons-days was similar between the two groups (23.0
      vs 21.5 episodes, age-adjusted IRR = 1.07 [95% CI, 0.90-1.27]). No significant
      difference was detected in in vivo response between the groups during both
      periods. CONCLUSION: Two malaria intermittent treatments targeting the peak
      transmission season reduced the annual incidence rate of clinical malaria by
      42.5% in an area with intense seasonal transmission. This simple strategy is
      likely to be one of the most effectives in reducing malaria burden in such areas.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT00623155.

PMID- 18611272
TI  - Transcriptome analysis for Caenorhabditis elegans based on novel expressed
      sequence tags.
AB  - BACKGROUND: We have applied a high-throughput pyrosequencing technology for
      transcriptome profiling of Caenorhabditis elegans in its first larval stage.
      Using this approach, we have generated a large amount of data for expressed
      sequence tags, which provides an opportunity for the discovery of putative novel
      transcripts and alternative splice variants that could be developmentally
      specific to the first larval stage. This work also demonstrates the successful
      and efficient application of a next generation sequencing methodology. RESULTS:
      We have generated over 30 million bases of novel expressed sequence tags from
      first larval stage worms utilizing high-throughput sequencing technology. We have
      shown that approximately 14% of the newly sequenced expressed sequence tags map
      completely or partially to genomic regions where there are no annotated genes or
      splice variants and therefore, imply that these are novel genetic structures.
      Expressed sequence tags, which map to intergenic (around 1000) and intronic
      regions (around 580), may represent novel transcribed regions, such as
      unannotated or unrecognized small protein-coding or non-protein-coding genes or
      splice variants. Expressed sequence tags, which map across intron-exon boundaries
      (around 300), indicate possible alternative splice sites, while expressed
      sequence tags, which map near the ends of known transcripts (around 600), suggest
      extension of the coding or untranslated regions. We have also discovered that
      intergenic and intronic expressed sequence tags, which are well conserved across
      different nematode species, are likely to represent non-coding RNAs. Lastly, we
      have incorporated available serial analysis of gene expression data generated
      from first larval stage worms, in order to predict novel transcripts that might
      be specifically or predominantly expressed in the first larval stage. CONCLUSION:
      We have demonstrated the use of a high-throughput sequencing methodology to
      efficiently produce a snap-shot of transcriptional activities occurring in the
      first larval stage of C. elegans development. Such application of this new
      sequencing technique allows for high-throughput, genome-wide experimental
      verification of known and novel transcripts. This study provides a more complete
      C. elegans transcriptome profile and, furthermore, gives insight into the
      evolutionary and biological complexity of this organism.

PMID- 18611273
TI  - Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect
      comparison.
AB  - BACKGROUND: Recent meta-analyses have found a survival advantage with gemcitabine
      based combinations over single agent gemcitabine in patients with advanced
      pancreatic cancer. There is paucity of evidence in the form of direct head-to
      head randomised controlled trials to determine which combinations are to be
      preferred. METHOD: Using the adjusted indirect comparison method proposed by
      Bucher et al, we have assessed randomised controlled trials of four gemcitabine
      based combinations namely gemcitabine plus a platinum compound or 5-fluorouracil
      or irinotecan or capecitabine. RESULTS: No particular combination was
      significantly superior to another, but the indirect evidence suggests some
      important trends. CONCLUSION: The strongest trends on indirect comparison are
      towards favouring gemcitabine plus capecitabine or gemcitabine plus a platinum
      compound over gemcitabine plus irinotecan, and to a lesser degree, over
      gemcitabine plus 5-fluorouracil.

PMID- 18611274
TI  - Kindlin-2 is required for myocyte elongation and is essential for myogenesis.
AB  - BACKGROUND: Integrins are required for normal muscle differentiation and
      disruptions in integrin signaling result in human muscle disease. The
      intracellular components that regulate integrin function during myogenesis are
      poorly understood. Unc-112 is an integrin-associated protein required for muscle
      development in C. elegans. To better understand the intracellular effectors of
      integrin signaling in muscle, we examined the mammalian homolog of Unc-112,
      kindlin-2. RESULTS: Kindlin-2 expression is upregulated during differentiation
      and highly enriched at sites of integrin localization. RNAi knockdown of kindlin
      2 in C2C12 cells results in significant abnormalities during the early stages of
      myogenesis. Specifically, differentiating myocytes lacking kindlin-2 are unable
      to elongate and fail to fuse into multinucleated myotubes. These changes are
      correlated with decreased cell substratum adhesion and increased cell motility.
      They are also associated with redistribution of a known kindlin-2 binding
      partner, integrin linked kinase (ILK), to the membrane insoluble subcellular
      fraction. CONCLUSION: In all, our study reveals kindlin-2 as a novel integrin
      adaptor protein important for muscle differentiation, and identifies it
      particularly as a critical regulator of myocyte elongation.

PMID- 18611275
TI  - Hypertonic saline reduces inflammation and enhances the resolution of oleic acid
      induced acute lung injury.
AB  - BACKGROUND: Hypertonic saline (HTS) reduces the severity of lung injury in
      ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury.
      However, the potential for HTS to modulate the resolution of lung injury is not
      known. We investigated the potential for hypertonic saline to modulate the
      evolution and resolution of oleic acid induced lung injury. METHODS: Adult male
      Sprague Dawley rats were used in all experiments. Series 1 examined the potential
      for HTS to reduce the severity of evolving oleic acid (OA) induced acute lung
      injury. Following intravenous OA administration, animals were randomized to
      receive isotonic (Control, n = 12) or hypertonic saline (HTS, n = 12), and the
      extent of lung injury assessed after 6 hours. Series 2 examined the potential for
      HTS to enhance the resolution of oleic acid (OA) induced acute lung injury.
      Following intravenous OA administration, animals were randomized to receive
      isotonic (Control, n = 6) or hypertonic saline (HTS, n = 6), and the extent of
      lung injury assessed after 6 hours. RESULTS: In Series I, HTS significantly
      reduced bronchoalveolar lavage (BAL) neutrophil count compared to Control [61.5
      +/- 9.08 versus 102.6 +/- 11.89 x 10(3) cells.ml-1]. However, there were no
      between group differences with regard to: A-a O2 gradient [11.9 +/- 0.5 vs. 12.0
      +/- 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In
      contrast, in Series 2, hypertonic saline significantly reduced histologic injury
      and reduced BAL neutrophil count [24.5 +/- 5.9 versus 46.8 +/- 4.4 x 10(3)
      cells.ml-1], and interleukin-6 levels [681.9 +/- 190.4 versus 1365.7 +/- 246.8
      pg.ml-1]. CONCLUSION: These findings demonstrate, for the first time, the
      potential for HTS to reduce pulmonary inflammation and enhance the resolution of
      oleic acid induced lung injury.

PMID- 18611276
TI  - Old and new cluster designs in emergency field surveys: in search of a one-fits
      all solution.
AB  - INTRODUCTION: Cluster surveys are frequently used to measure key nutrition and
      health indicators in humanitarian emergencies. The survey design of 30 clusters
      of 7 children (30 x 7) was initially proposed by the World Health Organization
      for measuring vaccination coverage, and later a design of 30 clusters of 30
      children (30 x 30) was introduced to measure acute malnutrition in emergency
      settings. Recently, designs of 33 clusters of 6 children (33 x 6) and 67 clusters
      of 3 children (67 x 3) have been proposed as alternatives that enable measurement
      of several key indicators with sufficient precision, while offering substantial
      savings in time. This paper explores expected effects of using 67 x 3, 33 x 6, or
      30 x 7 designs instead of a "standard" 30 x 30 design on precision and accuracy
      of estimates, and on time required to complete the survey. ANALYSIS: The 67 x 3,
      33 x 6, and 30 x 7 designs are expected to be more statistically efficient for
      measuring outcomes having high design effects (e.g., vaccination coverage,
      vitamin A distribution coverage, or access to safe water sources), and less
      efficient for measuring outcomes with more within-cluster variability, such as
      global acute malnutrition or anemia. Because of small sample sizes, these designs
      may not provide sufficient levels of precision to measure crude mortality rates.
      Given the small number (3 to 7) of survey subjects per cluster, it may be hard to
      select representative samples of subjects within clusters.The smaller sample size
      in these designs will likely result in substantial time savings. The magnitude of
      the savings will depend on several factors, including the average travel time
      between clusters. The 67 x 3 design will provide the least time savings. The 33 x
      6 and 30 x 7 designs perform similarly to each other, both in terms of
      statistical efficiency and in terms of time required to complete the survey.
      CONCLUSION: Cluster designs discussed in this paper may offer substantial time
      and cost savings compared to the traditional 30 x 30 design, and may provide
      acceptable levels of precision when measuring outcomes that have high
      intracluster homogeneity. Further investigation is required to determine whether
      these designs can consistently provide accurate point estimates for key outcomes
      of interest. Organizations conducting cluster surveys in emergency settings need
      to build their technical capacity in survey design to be able to calculate
      context-specific sample sizes individually for each planned survey.

PMID- 18611277
TI  - Cost-utility of a walking programme for moderately depressed, obese, or
      overweight elderly women in primary care: a randomised controlled trial.
AB  - BACKGROUND: There is a considerable public health burden due to physical
      inactivity, because it is a major independent risk factor for several diseases
      (e.g., type 2 diabetes, cardiovascular disease, moderate mood disorders neurotic
      diseases such as depression, etc.). This study assesses the cost utility of the
      adding a supervised walking programme to the standard "best primary care" for
      overweight, moderately obese, or moderately depressed elderly women. METHODS: One
      hundred six participants were randomly assigned to an interventional group (n =
      55) or a control group (n = 51). The intervention consisted of an invitation,
      from a general practitioner, to participate in a 6-month walking-based,
      supervised exercise program with three 50-minute sessions per week. The main
      outcome measures were the healthcare costs from the Health System perspective and
      quality adjusted life years (QALYs) using EuroQol (EQ-5D.) RESULTS: Of the
      patients invited to participate in the program, 79% were successfully recruited,
      and 86% of the participants in the exercise group completed the programme. Over 6
      months, the mean treatment cost per patient in the exercise group was 41 euros
      more than "best care". The mean incremental QALY of intervention was 0.132 (95%
      CI: 0.104-0.286). Each extra QALY gained by the exercise programme relative to
      best care cost 311 euros (95% CI, 143 euros-394 euros). The cost effectiveness
      acceptability curves showed a 90% probability that the addition of the walking
      programme is the best strategy if the ceiling of inversion is 350 euros/QALY.
      CONCLUSION: The invitation strategy and exercise programme resulted in a high
      rate of participation and is a feasible and cost-effective addition to best care.
      The programme is a cost-effective resource for helping patients to increase their
      physical activity, according to the recommendations of general practitioners.
      Moreover, the present study could help decision makers enhance the preventive
      role of primary care and optimize health care resources. TRIAL REGISTRATION:
      [ISRCTN98931797].

PMID- 18611278
TI  - Large scale variation in Enterococcus faecalis illustrated by the genome analysis
      of strain OG1RF.
AB  - BACKGROUND: Enterococcus faecalis has emerged as a major hospital pathogen. To
      explore its diversity, we sequenced E. faecalis strain OG1RF, which is commonly
      used for molecular manipulation and virulence studies. RESULTS: The 2,739,625
      base pair chromosome of OG1RF was found to contain approximately 232 kilobases
      unique to this strain compared to V583, the only publicly available sequenced
      strain. Almost no mobile genetic elements were found in OG1RF. The 64 areas of
      divergence were classified into three categories. First, OG1RF carries 39 unique
      regions, including 2 CRISPR loci and a new WxL locus. Second, we found nine
      replacements where a sequence specific to V583 was substituted by a sequence
      specific to OG1RF. For example, the iol operon of OG1RF replaces a possible
      prophage and the vanB transposon in V583. Finally, we found 16 regions that were
      present in V583 but missing from OG1RF, including the proposed pathogenicity
      island, several probable prophages, and the cpsCDEFGHIJK capsular polysaccharide
      operon. OG1RF was more rapidly but less frequently lethal than V583 in the mouse
      peritonitis model and considerably outcompeted V583 in a murine model of urinary
      tract infections. CONCLUSION: E. faecalis OG1RF carries a number of unique loci
      compared to V583, but the almost complete lack of mobile genetic elements
      demonstrates that this is not a defining feature of the species. Additionally,
      OG1RF's effects in experimental models suggest that mediators of virulence may be
      diverse between different E. faecalis strains and that virulence is not dependent
      on the presence of mobile genetic elements.

PMID- 18611279
TI  - Antimalarial drug use in general populations of tropical Africa.
AB  - BACKGROUND: The burden of Plasmodium falciparum malaria has worsened because of
      the emergence of chloroquine resistance. Antimalarial drug use and drug pressure
      are critical factors contributing to the selection and spread of resistance. The
      present study explores the geographical, socio-economic and behavioural factors
      associated with the use of antimalarial drugs in Africa. METHODS: The presence of
      chloroquine (CQ), pyrimethamine (PYR) and other antimalarial drugs has been
      evaluated by immuno-capture and high-performance liquid chromatography in the
      urine samples of 3,052 children (2-9 y), randomly drawn in 2003 from the general
      populations at 30 sites in Senegal (10), Burkina-Faso (10) and Cameroon (10).
      Questionnaires have been administered to the parents of sampled children and to a
      random sample of households in each site. The presence of CQ in urine was
      analysed as dependent variable according to individual and site characteristics
      using a random - effect logistic regression model to take into account the
      interdependency of observations made within the same site. RESULTS: According to
      the sites, the prevalence rates of CQ and PYR ranged from 9% to 91% and from 0%
      to 21%, respectively. In multivariate analysis, the presence of CQ in urine was
      significantly associated with a history of fever during the three days preceding
      urine sampling (OR = 1.22, p = 0.043), socio-economic level of the population of
      the sites (OR = 2.74, p = 0.029), age (2-5 y = reference level; 6-9 y OR = 0.76,
      p = 0.002), prevalence of anti-circumsporozoite protein (CSP) antibodies (low
      prevalence: reference level; intermediate level OR = 2.47, p = 0.023), proportion
      of inhabitants who lived in another site one year before (OR = 2.53, p = 0.003),
      and duration to reach the nearest tarmacked road (duration less than one hour =
      reference level, duration equal to or more than one hour OR = 0.49, p = 0.019).
      CONCLUSION: Antimalarial drug pressure varied considerably from one site to
      another. It was significantly higher in areas with intermediate malaria
      transmission level and in the most accessible sites. Thus, P. falciparum strains
      arriving in cross-road sites or in areas with intermediate malaria transmission
      are exposed to higher drug pressure, which could favour the selection and the
      spread of drug resistance.

PMID- 18611280
TI  - Housekeeping while brain's storming Validation of normalizing factors for gene
      expression studies in a murine model of traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury models are widely studied, especially through
      gene expression, either to further understand implied biological mechanisms or to
      assess the efficiency of potential therapies. A large number of biological
      pathways are affected in brain trauma models, whose elucidation might greatly
      benefit from transcriptomic studies. However the suitability of reference genes
      needed for quantitative RT-PCR experiments is missing for these models. RESULTS:
      We have compared five potential reference genes as well as total cDNA level
      monitored using Oligreen reagent in order to determine the best normalizing
      factors for quantitative RT-PCR expression studies in the early phase (0-48 h
      post-trauma (PT)) of a murine model of diffuse brain injury. The levels of 18S
      rRNA, and of transcripts of beta-actin, glyceraldehyde-3P-dehydrogenase (GAPDH),
      beta-microtubulin and S100beta were determined in the injured brain region of
      traumatized mice sacrificed at 30 min, 3 h, 6 h, 12 h, 24 h and 48 h post-trauma.
      The stability of the reference genes candidates and of total cDNA was evaluated
      by three different methods, leading to the following rankings as normalization
      factors, from the most suitable to the less: by using geNorm VBA applet, we
      obtained the following sequence: cDNA(Oligreen); GAPDH > 18S rRNA > S100beta >
      beta-microtubulin > beta-actin; by using NormFinder Excel Spreadsheet, we
      obtained the following sequence: GAPDH > cDNA(Oligreen) > S100beta > 18S rRNA >
      beta-actin > beta-microtubulin; by using a Confidence-Interval calculation, we
      obtained the following sequence: cDNA(Oligreen) > 18S rRNA; GAPDH > S100beta >
      beta-microtubulin > beta-actin. CONCLUSION: This work suggests that Oligreen cDNA
      measurements, 18S rRNA and GAPDH or a combination of them may be used to
      efficiently normalize qRT-PCR gene expression in mouse brain trauma injury, and
      that beta-actin and beta-microtubulin should be avoided. The potential of total
      cDNA as measured by Oligreen as a first-intention normalizing factor with a broad
      field of applications is highlighted. Pros and cons of the three methods of
      normalization factors selection are discussed. A generic time- and cost-effective
      procedure for normalization factor validation is proposed.

PMID- 18611282
TI  - Cardiovascular magnetic resonance of the charcoal heart.
AB  - We report a case of malignant melanoma metastasis to the heart presenting as
      complete heart block. The highlight of the case is to demonstrate that silent
      cardiac metastasis is not uncommon and CMR has the potential to characterize
      these cardiac metastases and should be used routinely as a screening tool for
      those cancers with a high chance of cardiac involvement.

PMID- 18611281
TI  - Tracing the colonization history of the Indian Ocean scops-owls (Strigiformes:
      Otus) with further insight into the spatio-temporal origin of the Malagasy
      avifauna.
AB  - BACKGROUND: The island of Madagascar and surrounding volcanic and coralline
      islands are considered to form a biodiversity hotspot with large numbers of
      unique taxa. The origin of this endemic fauna can be explained by two different
      factors: vicariance or over-water-dispersal. Deciphering which factor explains
      the current distributional pattern of a given taxonomic group requires robust
      phylogenies as well as estimates of divergence times. The lineage of Indian Ocean
      scops-owls (Otus: Strigidae) includes six or seven species that are endemic to
      Madagascar and portions of the Comoros and Seychelles archipelagos; little is
      known about the species limits, biogeographic affinities and relationships to
      each other. In the present study, using DNA sequence data gathered from six loci,
      we examine the biogeographic history of the Indian Ocean scops-owls. We also
      compare the pattern and timing of colonization of the Indian Ocean islands by
      scops-owls with divergence times already proposed for other bird taxa. RESULTS:
      Our analyses revealed that Indian Ocean islands scops-owls do not form a
      monophyletic assemblage: the Seychelles Otus insularis is genetically closer to
      the South-East Asian endemic O. sunia than to species from the Comoros and
      Madagascar. The Pemba Scops-owls O. pembaensis, often considered closely related
      to, if not conspecific with O. rutilus of Madagascar, is instead closely related
      to the African mainland O. senegalensis. Relationships among the Indian Ocean
      taxa from the Comoros and Madagascar are unresolved, despite the analysis of over
      4000 bp, suggesting a diversification burst after the initial colonization event.
      We also highlight one case of putative back-colonization to the Asian mainland
      from an island ancestor (O. sunia). Our divergence date estimates, using a
      Bayesian relaxed clock method, suggest that all these events occurred during the
      last 3.6 myr; albeit colonization of the Indian Ocean islands were not
      synchronous, O. pembaensis diverged from O. senegalensis about 1.7 mya while
      species from Madagascar and the Comoro diverged from their continental sister
      group about 3.6 mya. We highlight that our estimates coincide with estimates of
      diversification from other bird lineages. CONCLUSION: Our analyses revealed the
      occurrence of multiple synchronous colonization events of the Indian Ocean
      islands by scops-owls, at a time when faunistic exchanges involving Madagascar
      was common as a result of lowered sea-level that would have allowed the formation
      of stepping-stone islands. Patterns of diversification that emerged from the
      scops-owls data are: 1) a star-like pattern concerning the order of colonization
      of the Indian Ocean islands and 2) the high genetic distinctiveness among all
      Indian Ocean taxa, reinforcing their recognition as distinct species.

PMID- 18611283
TI  - The effect on the extracellular matrix of the deep fascia in response to leg
      lengthening.
AB  - BACKGROUND: Whereas the alterations of diverse tissues in cellular and molecular
      levels have been investigated during leg lengthening via microscopy and
      biochemical studies, little is known about the response of deep fascia. This
      study aims to investigate the changes of the extracellular matrix in deep fascia
      in response to leg lengthening. METHODS: Animal model of leg lengthening was
      established in New Zealand white rabbits. Distraction was initiated at a rate of
      1 mm/day and 2 mm/day in two steps, and preceded until increases of 10% and 20%
      in the initial length of tibia had been achieved. Alcian blue stain and
      picrosirius-polarization method were used for the study of the extracellular
      matrix of deep fascia samples. Leica DM LA image analysis system was used to
      investigate the quantitative changes of collagen type I and III. RESULTS: Alcian
      blue stain showed that glycosaminoglycans of fascia of each group were composed
      of chondroitin sulphate and heparin sulphate, but not of keratan sulphate. Under
      the polarization microscopy, the fascia consisted mainly of collagen type I.
      After leg lengthening, the percentage of collagen type III increased. The most
      similar collagen composition of the fascia to that of the normal fascia was
      detected at a 20% increase in tibia length achieved via a distraction rate of 1
      mm/d. CONCLUSION: The changes in collagen distribution and composition occur in
      deep fascia during leg lengthening. Although different lengthening schemes
      resulted in varied matrix changes, the most comparable collagen composition to be
      demonstrated under the scheme of a distraction rate of 1 mm/day and 20% increase
      in tibia length. Efficient fascia regeneration is initiated only in certain
      combinations of the leg load parameters including appropriate intensity and
      duration time, e.g., either low density distraction that persist a relatively
      short time or high distraction rates.

PMID- 18611284
TI  - Transvenous right ventricular pacing in a patient with tricuspid mechanical
      prosthesis.
AB  - We report a patient in whom permanent endocardial pacing was accomplished by
      passage of the electrode through a mechanical tricuspid valve. Echocardiography
      study showed a minimal tricuspid regurgitation.

PMID- 18611285
TI  - Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by
      high resolution melting.
AB  - BACKGROUND: A recurrent somatic mutation, E17K, in the pleckstrin homology domain
      of the AKT1 gene, has been recently described in breast, colorectal, and ovarian
      cancers. AKT1 is a pivotal mediator of signalling pathways involved in cell
      survival, proliferation and growth. The E17K mutation stimulates downstream
      signalling and exhibits transforming activity in vitro and in vivo. FINDINGS: We
      developed a sensitive high resolution melting (HRM) assay to detect the E17K
      mutation from formalin-fixed paraffin-embedded tumours. We screened 219 non-small
      cell lung cancer biopsies for the mutation using HRM analysis. Four samples were
      identified as HRM positive. Subsequent sequencing of those samples confirmed the
      E17K mutation in one of the cases. A rare single nucleotide polymorphism was
      detected in each of the remaining three samples. The E17K was found in one of the
      14 squamous cell carcinomas. No mutations were found in 141 adenocarcinomas and
      39 large cell carcinomas. CONCLUSION: The AKT1 E17K mutation is very rare in lung
      cancer and might be associated with tumorigenesis in squamous cell carcinoma. HRM
      represents a rapid cost-effective and robust screening of low frequency mutations
      such as AKT1 mutations in clinical samples.

PMID- 18611286
TI  - The Alternative Splicing Mutation Database: a hub for investigations of
      alternative splicing using mutational evidence.
AB  - BACKGROUND: Some mutations in the internal regions of exons occur within splicing
      enhancers and silencers, influencing the pattern of alternative splicing in the
      corresponding genes. To understand how these sequence changes affect splicing, we
      created a database of these mutations. FINDINGS: The Alternative Splicing
      Mutation Database (ASMD) serves as a repository for all exonic mutations not
      associated with splicing junctions that measurably change the pattern of
      alternative splicing. In this initial published release (version 1.2), only human
      sequences are present, but the ASMD will grow to include other organisms, (see
      Availability and requirements section for the ASMD web address).This relational
      database allows users to investigate connections between mutations and features
      of the surrounding sequences, including flanking sequences, RNA secondary
      structures and strengths of splice junctions. Splicing effects of the mutations
      are quantified by the relative presence of alternative mRNA isoforms with and
      without a given mutation. This measure is further categorized by the accuracy of
      the experimental methods employed. The database currently contains 170 mutations
      in 66 exons, yet these numbers increase regularly.We developed an algorithm to
      derive a table of oligonucleotide Splicing Potential (SP) values from the ASMD
      dataset. We present the SP concept and tools in detail in our corresponding
      article. CONCLUSION: The current data set demonstrates that mutations affecting
      splicing are located throughout exons and might be enriched within local RNA
      secondary structures. Exons from the ASMD have below average splicing junction
      strength scores, but the difference is small and is judged not to be significant.

PMID- 18611287
TI  - Calculation of splicing potential from the Alternative Splicing Mutation
      Database.
AB  - BACKGROUND: The Alternative Splicing Mutation Database (ASMD) presents a
      collection of all known mutations inside human exons which affect splicing
      enhancers and silencers and cause changes in the alternative splicing pattern of
      the corresponding genes. FINDINGS: An algorithm was developed to derive a
      Splicing Potential (SP) table from the ASMD information. This table characterizes
      the influence of each oligonucleotide on the splicing effectiveness of the exon
      containing it. If the SP value for an oligonucleotide is positive, it promotes
      exon retention, while negative SP values mean the sequence favors exon skipping.
      The merit of the SP approach is the ability to separate splicing signals from a
      wide range of sequence motifs enriched in exonic sequences that are attributed to
      protein-coding properties and/or translation efficiency. Due to its direct
      derivation from observed splice site selection, SP has an advantage over other
      computational approaches for predicting alternative splicing. CONCLUSION: We show
      that a vast majority of known exonic splicing enhancers have highly positive
      cumulative SP values, while known splicing silencers have core motifs with
      strongly negative cumulative SP values. Our approach allows for computation of
      the cumulative SP value of any sequence segment and, thus, gives researchers the
      ability to measure the possible contribution of any sequence to the pattern of
      splicing.

PMID- 18611288
TI  - Analysis of the FoodNet case-control study of sporadic Salmonella serotype
      Enteritidis infections using persons infected with other Salmonella serotypes as
      the comparison group.
AB  - Use of well persons as the comparison group for laboratory-confirmed cases of
      sporadic salmonellosis may introduce ascertainment bias into case-control
      studies. Data from the 1996-1997 FoodNet case-control study of laboratory
      confirmed Salmonella serogroups B and D infection were used to estimate the
      effect of specific behaviours and foods on infection with Salmonella serotype
      Enteritidis (SE). Persons with laboratory-confirmed Salmonella of other serotypes
      acted as the comparison group. The analysis included 173 SE cases and 268 non-SE
      controls. SE was associated with international travel, consumption of chicken
      prepared outside the home, and consumption of undercooked eggs prepared outside
      the home in the 5 days prior to diarrhoea onset. SE phage type 4 was associated
      with international travel and consumption of undercooked eggs prepared outside
      the home. The use of ill controls can be a useful tool in identifying risk
      factors for sporadic cases of Salmonella.

PMID- 18611289
TI  - Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in
      post-mortem brain of teenage suicide victims.
AB  - Teenage suicide is a major public health concern, but its neurobiology is not
      very well understood. Stress and major mental disorders are major risk factors
      for suicidal behaviour, and it has been shown that brain-derived neurotrophic
      factor (BDNF) and its receptor tyrosine kinase B (TrkB) are not only regulated by
      stress but are also altered in these illnesses. We therefore examined if
      BDNF/TrkB signalling is altered in the post-mortem brain of teenage suicide
      victims. Protein and mRNA expression of BDNF and of TrkB receptors were
      determined in the prefrontal cortex (PFC), Brodmann's Area 9 (BA 9), and
      hippocampus obtained from 29 teenage suicide victims and 25 matched normal
      control subjects. Protein expression was determined using the Western blot
      technique; mRNA levels by a quantitative RT-PCR technique. The protein expression
      of BDNF was significantly decreased in the PFC of teenage suicide victims
      compared with normal control subjects, whereas no change was observed in the
      hippocampus. Protein expression of TrkB full-length receptors was significantly
      decreased in both PFC and hippocampus of teenage suicide victims without any
      significant changes in the truncated form of TrkB receptors. mRNA expression of
      both BDNF and TrkB was significantly decreased in the PFC and hippocampus of
      teenage suicide victims compared with normal control subjects. These studies
      indicate a down-regulation of both BDNF and its receptor TrkB in the PFC and
      hippocampus of teenage suicide victims, which suggests that stress and altered
      BDNF may represent a major vulnerability factor in teenage suicidal behaviour.

PMID- 18611290
TI  - Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene
      transcription and protect dopaminergic neurons.
AB  - Parkinson's disease (PD) is characterized by the selective and progressive loss
      of dopaminergic (DA) neurons in the midbrain substantia nigra. Currently,
      available treatment is unable to alter PD progression. Previously, we
      demonstrated that valproic acid (VPA), a mood stabilizer, anticonvulsant and
      histone deacetylase (HDAC) inhibitor, increases the expression of glial cell line
      derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF)
      in astrocytes to protect DA neurons in midbrain neuron-glia cultures. The present
      study investigated whether these effects are due to HDAC inhibition and histone
      acetylation. Here, we show that two additional HDAC inhibitors, sodium butyrate
      (SB) and trichostatin A (TSA), mimic the survival-promoting and protective
      effects of VPA on DA neurons in neuron-glia cultures. Similar to VPA, both SB and
      TSA increased GDNF and BDNF transcripts in astrocytes in a time-dependent manner.
      Furthermore, marked increases in GDNF promoter activity and promoter-associated
      histone H3 acetylation were noted in astrocytes treated with all three compounds,
      where the time-course for acetylation was similar to that for gene transcription.
      Taken together, our results indicate that HDAC inhibitors up-regulate GDNF and
      BDNF expression in astrocytes and protect DA neurons, at least in part, through
      HDAC inhibition. This study indicates that astrocytes may be a critical
      neuroprotective mechanism of HDAC inhibitors, revealing a novel target for the
      treatment of psychiatric and neurodegenerative diseases.

PMID- 18611291
TI  - Differential long-term effects of MDMA on the serotoninergic system and
      hippocampal cell proliferation in 5-HTT knock-out vs. wild-type mice.
AB  - Although numerous studies investigated the mechanisms underlying 3,4
      methylenedioxymethamphetamine (MDMA)-induced neurotoxicity, little is known about
      its long-term functional consequences on 5-HT neurotransmission in mice. This led
      us to evaluate the delayed effects of MDMA exposure on the 5-HT system, using in
      vitro and in-vivo approaches in both 5-HTT wild-type and knock-out mice. Acute
      MDMA in-vitro application on slices of the dorsal raphe nucleus (DRN) induced
      concentration-dependent 5-HT release and 5-HT cell firing inhibition. Four weeks
      after MDMA administration (20 mg/kg b.i.d for 4 d), a 2-fold increase in the
      potency of the 5-HT1A receptor agonist ipsapirone to inhibit the discharge of DRN
      5-HT neurons and a larger hypothermic response to 8-OH-DPAT were observed in MDMA
      compared to saline-treated mice. This adaptive 5-HT1A autoreceptor
      supersensitivity was associated with decreases in 5-HT levels but no changes of
      [3H]citalopram binding in brain. Long-term MDMA treatment also induced a 30%
      decrease in BrdU labelling of proliferating hippocampal cells and an increased
      immobility duration in the forced swim test suggesting a depressive-like
      behaviour induced by MDMA treatment. All these effects were abolished in 5-HTT-/-
      knock-out mice. These data indicated that, in mice, MDMA administration induced a
      delayed adaptive supersensitivity of 5-HT1A autoreceptors in the DRN, a deficit
      in hippocampal cell proliferation and a depressive-like behaviour. These 5-HTT
      dependent effects, opposite to those of antidepressants, might contribute to MDMA
      induced mood disorders.

PMID- 18611292
TI  - The His452Tyr variant of the gene encoding the 5-HT2A receptor is specifically
      associated with consolidation of episodic memory in humans.
AB  - Basic research has shown that serotonin plays an important role in memory
      formation. Accordingly, genetic variation of serotonin receptors can be expected
      to affect memory and to underlie, in part, the heritability of memory capacity. A
      study by de Quervain and colleagues found a highly significant association of the
      functional 5-HT2A receptor variant His452Tyr (rs6314) with long-term memory. We
      replicated this finding in a cohort of 133 adults (mean age 43.5 yr). Carriers of
      the Tyr allele showed poorer verbal delayed recall and recognition, while
      immediate recall and additional measures of attentional and executive function
      were not affected by the His452Tyr genotype. Results suggest a possible role of 5
      HT2A receptors in memory consolidation. Serotonergic drugs may have the potential
      to improve memory.

PMID- 18611294
TI  - Laparoscopic cervical cerclage.

PMID- 18611293
TI  - What predicts attrition in second step medication treatments for depression?: a
      STAR*D Report.
AB  - Attrition rates are high during treatment for major depressive disorder (MDD),
      and patients who drop out are less likely to reach remission. This report
      evaluates the incidence, timing, and predictors of attrition during second-step
      medication treatment. Outpatients in the multisite Sequenced Treatment
      Alternatives to Relieve Depression (STAR*D) study receiving a medication
      augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an
      unsatisfactory outcome with citalopram were evaluated to determine attrition
      rates and pretreatment sociodemographic or clinical predictors of attrition.
      Twenty percent of participants receiving a medication augmentation and 27%
      receiving a medication switch dropped out before 12 wk in the second treatment
      step. Remission rates were lower for dropouts [7% vs. 43% (medication
      augmentation); 12% vs. 31% (medication switch)]. For medication augmentation,
      Black and other non-Caucasian races, Hispanic ethnicity, younger age, family
      history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less
      symptom improvement with initial citalopram treatment, and greater symptom
      severity when beginning augmentation were associated with attrition. For
      medication switch, Black and other non-Caucasian races, younger age, more
      melancholic features, and lower exit doses but more severe side-effects with
      citalopram treatment were associated with attrition. Minority status, younger
      age, and greater difficulty with the first treatment step are risk factors for
      attrition in the second treatment step. Focus on patients with attrition risk
      factors for medication augmentation or switch strategies may enhance retention
      and improve outcomes.

PMID- 18611296
TI  - Green meetings.

PMID- 18611298
TI  - The role of decidual natural killer cells in normal placentation and in the
      pathogenesis of preeclampsia.
AB  - Adequate invasion of the human placenta during the first weeks of pregnancy is a
      critical step in ensuring both fetal and maternal health. A rapidly expanding
      body of evidence suggests that decidual natural killer (dNK) cells, a distinct
      population of CD56brightCD16- lymphocytes, are key regulators of this complex
      process. Experiments using murine models and in vitro evidence using human tissue
      cultures suggest that dNK cells modulate extravillous trophoblast (EVT) invasion
      and remodelling of maternal spiral arteries via both contact-dependent and
      contact-independent mechanisms. In addition, the differential expression of
      surface receptors by dNK cells may have a role in determining reproductive
      success through modulation of the maternal immune system at the time of
      implantation and placentation. The roles of cytokines, chemokines, and growth
      factors secreted by dNK cells and their influence on EVT migration, invasion, and
      pseudovasculogenesis are of particular interest. We reviewed the available
      experimental evidence related to the functional relationships between dNK cells
      and trophoblasts at the time of placentation to elucidate potential clinical
      correlations with human pathologies, including preeclampsia, recurrent pregnancy
      loss, IVF failure, and placenta accreta.

PMID- 18611299
TI  - Obesity in pregnancy: pre-conceptional to postpartum consequences.
AB  - OBJECTIVE: To review the effects of obesity on reproduction and pregnancy
      outcome. METHODS: A search of the literature was performed using key word
      searching and citation snowballing to identify English language articles
      published between January 1, 2000, and December 31, 2006, on the subject of
      obesity and its effects on pregnancy. Once the articles were identified, a
      thorough review of all results was conducted. Results and conclusions were
      compiled and summarized. RESULTS: Obesity during pregnancy was linked with
      maternal complications ranging from effects on fertility to effects on delivery
      and in the postpartum period, as well as many complications affecting the fetus
      and newborn. The maternal complications associated with obesity included
      increased risks of infertility, hypertensive disorders, gestational diabetes
      mellitus, and delivery by Caesarean section. Fetal complications included
      increased risks of macrosomia, intrauterine fetal death and stillbirth, and
      admission to the neonatal intensive care unit. CONCLUSION: Obesity causes
      significant complications for the mother and fetus. Interventions directed
      towards weight loss and prevention of excessive weight gain must begin in the pre
      conception period. Obstetrical care providers must counsel their obese patients
      regarding the risks and complications conferred by obesity and the importance of
      weight loss. Maternal and fetal surveillance may need to be heightened during
      pregnancy; a multidisciplinary approach is useful. Women need to be informed
      about both maternal and fetal complications and about the measures that are
      necessary to optimize outcome, but the most important measure is to address the
      issue of weight prior to pregnancy.

PMID- 18611300
TI  - Women's knowledge, attitudes, and intentions concerning Human Papillomavirus
      vaccination: findings of a waiting room survey of obstetrics-gynaecology
      outpatients.
AB  - OBJECTIVE: To assess women's knowledge, attitudes, and behaviours related to
      Human Papillomavirus (HPV) and HPV vaccination. METHODS: A self-administered
      questionnaire was completed by 98 women (90.7% response rate) attending a
      hospital-based obstetrics and gynaecology outpatient clinic in a mid-size Ontario
      city. RESULTS: Women had a moderate level of knowledge of general HPV-related
      issues, but lacked information about the ability of barrier contraception to
      prevent HPV and about characteristics of HPV vaccination. Women were strongly
      supportive of HPV vaccination for both male and female teenagers, but reported
      low levels of intention to receive vaccination themselves. Physician
      recommendation was the most influential factor in women intention to be
      vaccinated, and younger women were more likely to say they intended to be
      vaccinated. HPV-related knowledge, level of education, and number of previous
      sexual partners were unrelated to women's intentions to receive HPV vaccination.
      CONCLUSION: Findings indicate that women's knowledge about HPV vaccination is
      inconsistent, that women are supportive of vaccinating both male and female
      teenagers, and that physician recommendation and younger age are associated with
      women's interest in receiving the vaccine.

PMID- 18611301
TI  - Leiomyosarcoma diagnosed six years after laparoscopic electromyolysis.
AB  - BACKGROUND: Making a histologic diagnosis of leiomyosarcoma in the specimen from
      a hysterectomy performed for suspected benign fibroids is rare. Currently, there
      are no reliable diagnostic tools to diagnose uterine sarcomas preoperatively.
      CASE: A 38-year-old woman presented with menorrhagia and a uterine fibroid
      measuring 6.0 cm x 8.1 cm x 6.2 cm on ultrasonography. The patient underwent a
      laparoscopic myolysis with 50% shrinkage of the fibroid volume at follow-up after
      six months. Six years after myolysis, the patient presented with right lower
      quadrant pain and a rapidly enlarging uterus. Hysterectomy and bilateral salpingo
      oophorectomy was performed and a diagnosis of leiomyosarcoma was histologically
      confirmed. CT scan was performed biannually after hysterectomy. One year after
      surgery, the patient presented with radiologic evidence of a right pulmonary
      nodule. The nodule was excised thoracoscopically and histologic examination
      demonstrated metastatic leiomyosarcoma. One year later, another pulmonary lesion
      appeared in the left lung and was excised thoracoscopically. Again, histological
      assessment showed metastatic leiomyosarcoma. This patient has remained healthy
      and asymptomatic for two years since the last thoracoscopic excision of the
      leiomyosarcoma metastasis. CONCLUSION: The current trend in treatment for
      symptomatic fibroids is therapy sparing the uterus. Such treatment includes both
      medical therapy and fibroid necrosing therapies such as vascular occlusion,
      embolization, and thermal coagulation technologies. Women considering uterus
      sparing treatment should be advised of the potential risk of uterine malignancy,
      even though that risk is quite minimal (< 0.5%). A delay in the diagnosis of
      uterine malignancy may ultimately compromise long-term survival.

PMID- 18611302
TI  - Medications for restless legs syndrome in pregnancy.
AB  - According to epidemiological data, pregnant women have a two or three times
      higher risk of experiencing restless legs syndrome (RLS) than the general
      population. Current evidence suggests that dopaminergic dysfunction, impaired
      iron homeostasis, and genetic predisposition may be involved in the
      pathophysiology of RLS. Four classes of medications have been used for patients
      with RLS, but pregnancy elicits a therapeutic concern. Although two dopamine
      agonists, ropinirole and pramipexole, have been approved by the FDA for the
      treatment of RLS and are currently the first-line treatment for daily symptoms,
      there is very little information on the teratogenic risks of these new
      medications. Therefore, they are not currently recommended for use during
      pregnancy. Medications with a more extensive safety record in pregnancy include
      opioids; antiepileptics, such as carbamazepine and gabapentin; and certain
      benzodiazepines. Ruling out iron deficiency should be an integral part of a
      treatment plan for RLS in pregnancy. Before management with medication is
      introduced, every patient should be assessed for iron status with measurement of
      serum ferritin.

PMID- 18611303
TI  - Ethical issues associated with the introduction of new surgical devices, or just
      because we can, doesn't mean we should.
AB  - Surgical devices are often marketed before there is good evidence of their safety
      and effectiveness. Our paper discusses the ethical issues associated with the
      early marketing and use of new surgical devices from the perspectives of the six
      groups most concerned. Health Canada, which is responsible for licensing new
      surgical devices, should amend their requirements to include rigorous clinical
      trials that provide data on effectiveness and safety for each new product before
      it is marketed. Industry should comply with all Health Canada requirements to
      obtain licenses for new products. Until Health Canada requires effectiveness and
      safety data, industry should cooperate with physicians in appropriate studies
      before releasing new products and should make balanced presentations of all the
      available evidence. Surgeons should, before using a new surgical device, assess
      the evidence on its effectiveness and safety and ensure they are properly trained
      and competent in using the device. Surgeons should provide their patients with an
      evaluation of the available evidence and inform them about possible complications
      and the surgeon's level of experience with the new device. Patients, who should
      be given an honest evaluation of the available evidence, possible complications,
      and the surgeon's experience, should be encouraged to evaluate the evidence and
      information to their own satisfaction to ensure that fully informed consent is
      given. Health institutions, responsible for regulating practice within their
      walls, should review new devices for safety, effectiveness, and economic impacts,
      before allowing their use. They should also limit the use of new surgical devices
      to surgeons trained and competent in the new technology. Professional societies
      should provide guidance on the early adoption of new surgical devices and
      technologies. We urge all those involved in the development, licensing, and use
      of new surgical devices to aim for higher ethical standards to protect the health
      and safety of patients requiring surgery. The lowest acceptable ethical standard
      would require device manufacturers to provide surgeons with accurate and timely
      information on the efficacy and safety of their products, allowing surgeons and
      patients to evaluate the evidence (and the significance of information not yet
      available) before surgery.

PMID- 18611304
TI  - Guidelines for the management of herpes simplex virus in pregnancy.
AB  - OBJECTIVE: To provide recommendations for the management of genital herpes
      infection in women who want to get pregnant or are pregnant and for the
      management of genital herpes in pregnancy and strategies to prevent transmission
      to the infant. OUTCOMES: More effective management of complications of genital
      herpes in pregnancy and prevention of transmission of genital herpes from mother
      to infant. EVIDENCE: Medline was searched for articles published in French or
      English related to genital herpes and pregnancy. Additional articles were
      identified through the references of these articles. All study types and
      recommendation reports were reviewed. VALUES: Recommendations were made according
      to the guidelines developed by the Canadian Task Force on Preventive Health Care.

PMID- 18611306
TI  - Ginseng ameliorates chronic histopathologic changes in a murine model of asthma.
AB  - Currently, asthma therapies are effective in reducing inflammation but airway
      remodeling is poorly responsive to these agents. New therapeutic options that
      have fewer side effects and reverse chronic changes in the lungs are essential.
      This study aimed to determine the efficacy of oral administration of ginseng on
      lung histopathology in a murine model of chronic asthma. BALB/c mice were divided
      into four groups: control, placebo, ginseng, and dexamethasone. All mice except
      those in the control group were sensitized and challenged with ovalbumin. Then,
      mice in the ginseng group were given 2 gr/kg per day of ginseng and mice in the
      dexamethasone group received 1 mg/kg per day of dexamethasone via orogastic
      gavage once daily for 1 week. Lung histopathology was evaluated by using light
      and electron microscopy in all groups. All of the chronic changes of airways in
      the ginseng group were significantly ameliorated when compared with the placebo
      group. When compared with the dexamethasone group, the ginseng group had
      significantly lower numbers of mast cell count. Thicknesses of basement membrane,
      epithelium, and subepithelial smooth muscle were not statistically different
      between the ginseng and dexamethasone groups. Goblet cell numbers were much more
      reduced in the dexamethasone group. Ginseng is effective in resolving the
      established chronic histopathological changes of the lungs in the murine model of
      asthma.

PMID- 18611307
TI  - Enhancing a primary care environment: a case study of effects on patients and
      staff in a single general practice.
AB  - BACKGROUND: Few studies have examined the effect on patients and staff of the
      physical environment in primary care facilities. AIM: To explore changes in
      patient and staff satisfaction, patient anxiety, and patient-doctor communication
      when a GP surgery moves from old premises to enhanced purpose-built
      accommodation. DESIGN OF STUDY: Questionnaire surveys, interviews, and focus
      groups pre- and post move. SETTING: An urban general practice in Bristol. METHOD:
      Patient questionnaires assessed anxiety (Spielberger State-Trait Anxiety
      Inventory; STAI), satisfaction with the environment, and communication during the
      consultation. Staff questionnaires assessed satisfaction with the environment and
      job satisfaction. Qualitative methods explored patient and staff views in more
      depth. RESULTS: A total of 1118 pre-move and 954 post-move patient questionnaires
      showed significant increases in satisfaction scores for reception/waiting areas
      (mean 6.46, 95% confidence interval [CI]=5.97 to 6.95) and consulting rooms (mean
      3.80, 95% CI=3.44 to 4.15) in the new premises. Patients' satisfaction with
      patient-doctor communication also increased (mean 0.88, 95% CI=0.30 to 1.46) and
      anxiety scores were significantly reduced before and after the consultation in
      the new premises compared with the old (STAI mean difference before consultation
      0.72, 95% CI=0.37 to 1.08; mean after consultation 0.37, 95% CI=0.03 to 0.72).
      Patients highlighted the increased space and light, more modern appearance,
      greater comfort, and novel works of art in the new surgery. Staff workplace
      satisfaction increased significantly after moving and remained higher than in the
      old building. CONCLUSION: This large-scale study examining the effects of a UK
      primary care environment on patients and staff shows that an enhanced environment
      is associated with improvements in patients' perception of patient-doctor
      communication, reduction in anxiety, and increases in patient and staff
      satisfaction.

PMID- 18611309
TI  - The NHS at 60: time to end the fairy tale.

PMID- 18611310
TI  - Your general practice environment can improve your community's health.

PMID- 18611311
TI  - Do you have your own doctor, doctor? Tackling barriers to health care.

PMID- 18611312
TI  - Does distance matter? Geographical variation in GP out-of-hours service use: an
      observational study.
AB  - BACKGROUND: GP cooperatives are typically based in emergency primary care
      centres, and patients are frequently required to travel to be seen. Geography is
      a key determinant of access, but little is known about the extent of geographical
      variation in the use of out-of-hours services. AIM: To examine the effects of
      distance and rurality on rates of out-of-hours service use. DESIGN OF STUDY:
      Geographical analysis based on routinely collected data on telephone calls in
      June (n=14 482) and December (n=19 747), and area-level data. SETTING: Out-of
      hours provider in Devon, England serving nearly 1 million patients. METHOD:
      Straight-line distance measured patients' proximity to the primary care centre.
      At area level, rurality was measured by Office for National Statistics Rural and
      Urban Classification (2004) for output areas, and deprivation by The Index of
      Multiple Deprivation (2004). RESULTS: Call rates decreased with increasing
      distance: 172 (95% confidence interval [CI]=170 to 175) for the first (nearest)
      distance quintile, 162 (95% CI=159 to 165) for the second, and 159 (95% CI=156 to
      162) per thousand patients/year for the third quintile. Distance and deprivation
      predicted call rate. Rates were highest for urban areas and lowest for sparse
      villages and hamlets. The greatest urban/rural variation was in patients aged 0-4
      years. Rates were higher in deprived areas, but the effect of deprivation was
      more evident in urban than rural areas. CONCLUSION: There is geographical
      variation in out-of-hours service use. Patients from rural areas have lower call
      rates, but deprivation appears to be a greater determinant in urban areas.
      Geographical barriers must be taken into account when planning and delivering
      services.

PMID- 18611314
TI  - Physical and social predictors of partner abuse in women attending general
      practice: a cross-sectional study.
AB  - BACKGROUND: Intimate partner abuse causes significant morbidity and mortality in
      women attending general practice. Currently there is insufficient evidence for
      screening all women but case finding of women at risk of intimate partner abuse
      is recommended. AIM: To develop physical symptoms and sociodemographic indicators
      for partner abuse for women attending general practice. DESIGN OF STUDY:
      Descriptive, cross-sectional survey. SETTING: Thirty general practices in
      Victoria, Australia. METHOD: A total of 1257 consecutive women attending general
      practice (response rate 77%) were screened for a history of partner abuse using a
      self-report questionnaire. The presence of partner abuse in the last 12 months
      was measured by the Composite Abuse Scale. RESULTS: Women who reported more than
      two physical symptoms in the last month were more likely to report experiencing
      partner abuse in the last 12 months (3-5 symptoms, odds ratio [OR]=2.32, 95%
      confidence interval [CI]=1.55 to 3.48; 6-15 symptoms OR=3.47, 95% CI=2.21 to
      5.47). Many individual physical symptoms were associated with partner abuse in
      the bivariable analysis. Multivariable analysis showed clinical indicators of
      partner abuse (excluding the strong association with depression) which included
      sociodemographic features (age, separated/divorced, low education, low income, no
      private insurance) and physical symptoms (diarrhoea, tiredness, chest pain).
      CONCLUSION: Clinicians should be alert for current and past partner abuse in
      women who are separated/divorced, on low incomes, have poor education, or have
      multiple physical symptoms in the past month. Future research questions include
      what interventions would work for women who have been or are being abused once
      identified.

PMID- 18611313
TI  - A new GP with special interest headache service: observational study.
AB  - BACKGROUND: There is poor access to neurology services for patients in the
      community. AIM: To describe the training of GPs with special interest (GPwSI) in
      headache and the setting up of a GPwSI clinic in general practice, and report on
      a comparison with the existing neurology service in terms of case severity,
      patient satisfaction, and cost. DESIGN OF STUDY: New service provision and
      evaluation by a questionnaire survey. SETTING: General practice and hospital
      neurology service in inner-city London. METHOD: The intervention involved
      training GPs as GPwSIs and setting up a GP headache service. A questionnaire
      survey was conducted, measuring headache impact, satisfaction, and cost
      estimates. RESULTS: Headache impact was not significantly different between the
      two groups of patients, referred to hospital and to a GPwSI. Patients were
      significantly more satisfied with the GPwSI service, particularly that the
      service was effective in helping to relieve their symptoms (89% versus 76%;
      adjusted odds ratio=7.7; 95% confidence interval=2.7 to 22.4). The cost per first
      appointment was estimated to be pound sterling 136, with pound sterling 68 for
      subsequent contacts. These are lower than costs for neurologist contacts.
      CONCLUSION: GPwSI services can satisfy the needs of patients with similar
      headache impact at costs that are lower than those for secondary care services.

PMID- 18611315
TI  - Multimorbidity and risk among patients with established cardiovascular disease: a
      cohort study.
AB  - BACKGROUND: Most patients managed in primary care have more than one condition.
      Multimorbidity presents challenges for the patient and the clinician, not only in
      terms of the process of care, but also in terms of management and risk
      assessment. AIM: To examine the effect of the presence of chronic kidney disease
      and diabetes on mortality and morbidity among patients with established
      cardiovascular disease. DESIGN OF STUDY: Retrospective cohort study. SETTING:
      Random selection of 35 general practices in the west of Ireland. METHOD: A
      practice-based sample of 1609 patients with established cardiovascular disease
      was generated in 2000-2001 and followed for 5 years. The primary endpoint was
      death from any cause and the secondary endpoint was a cardiovascular composite
      endpoint that included death from a cardiovascular cause or any of the following
      cardiovascular events: myocardial infarction, heart failure, peripheral vascular
      disease, or stroke. RESULTS: Risk of death from any cause was significantly
      increased in patients with increased multimorbidity (P<0.001), as was the risk of
      the cardiovascular composite endpoint (P<0.001). Patients with cardiovascular
      disease and diabetes had a similar survival pattern to those with cardiovascular
      disease and chronic kidney disease, but experienced more cardiovascular events.
      CONCLUSION: Level of multimorbidity is an independent predictor of prognosis
      among patients with established cardiovascular disease. In such patients, the
      presence of chronic kidney disease carries a similar mortality risk to diabetes.
      Multimorbidity may be a useful factor in prioritising management of patients in
      the community with significant cardiovascular risk.

PMID- 18611316
TI  - Identifying individuals for primary cardiovascular disease prevention in UK
      general practice: priorities and resource implications.
AB  - Targeted cardiovascular disease prevention relies on risk-factor information held
      in primary care records. A risk algorithm, the 'e-Nudge', was applied to data
      from a population of >or=50-year-olds in 19 West Midlands practices, to identify
      those individuals at risk of cardiovascular disease. Altogether, 5.9% were
      identified aged 50-74 years at >or=20% 10-year risk based on existing data, and a
      further 26.4% were potentially at risk but had missing risk-factor information;
      9.2% of patients aged over 50 years with established cardiovascular disease had
      at least one modifiable risk factor outside the audit target of the Quality and
      Outcomes Framework. Implications for resource allocation are discussed.

PMID- 18611317
TI  - Further observations on enablement.

PMID- 18611319
TI  - Preoperative anaemia.

PMID- 18611318
TI  - Doctors as patients: a systematic review of doctors' health access and the
      barriers they experience.
AB  - BACKGROUND: The need to improve doctors' access to health care by reducing the
      barriers they experience has been regularly described in the literature, yet the
      barriers experienced are not well defined, despite the volume of expert opinion
      in this area. AIM: To define what is known about doctors' access to health care
      from the data within the current literature. DESIGN OF STUDY: A systematic review
      of studies of doctors' health access. METHOD: A systematic search of MEDLINE and
      CINAHL, supplemented by citation searches and searches of the grey literature,
      identified both quantitative and qualitative studies. Two reviewers used specific
      criteria for inclusion of studies and quality assessment. The data were tabulated
      and analysed. RESULTS: Twenty-six articles met the inclusion criteria. The
      paucity of data and the overall poor quality of those data are highlighted.
      Despite this, many doctors appear to have a GP, but this does not ensure adequate
      health access. Systemic barriers to healthcare access (long hours and cultural
      issues) are more significant than individual barriers. CONCLUSION: Expert opinion
      in this field is supported by poor-quality data. The current knowledge reveals
      important similarities between doctors and the general population in their
      healthcare access, especially with mental health issues. Understanding this may
      help the medical profession to respond to these issues of 'doctors' health' more
      effectively.

PMID- 18611320
TI  - Real life ethics.

PMID- 18611321
TI  - 'Home Office syndrome'.

PMID- 18611322
TI  - Death certification post Shipman.

PMID- 18611323
TI  - Public squalor, private squalor.

PMID- 18611324
TI  - Alford's theoretical political framework and its application to interests in
      health care now.

PMID- 18611325
TI  - Architecture and general practice.

PMID- 18611326
TI  - A patient's diary: episode 19--a shocking experience.

PMID- 18611331
TI  - [Clinical concept and strategic determination in emergency medicine].

PMID- 18611332
TI  - [Effect of ligation of mesenteric lymph duct on inflammation response of liver in
      hemorrhagic shock in rats].
AB  - OBJECTIVE: To observe the effect of ligation of mesenteric lymph duct on changes
      in free radicals and pro-inflammatory mediators in the liver of rats with serious
      hemorrhagic shock at different periods, and explore the effect of blockage of
      intestinal lymphatic pathway on inflammation response of liver. METHODS: Seventy
      eight male Wistar rats were randomly divided into the sham group (n=6), shock
      group (n=42), and ligation group (n=30). The model of serious hemorrhagic shock
      was reproduced in shock group and ligation group. Mesenteric lymph was blocked by
      ligating mesenteric lymph duct in ligation group after resuscitation. Six rats
      were sacrificed at 0, 1, 3, 6, 12, and 24 hours, and the livers were harvested
      and homogenized for the determination of malondialdehyde (MDA), nitric oxide
      (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-6 (IL-6) and myeloperoxidase (MPO)
      activity. The expression of inducible nitric oxide synthase (iNOS) mRNA in liver
      was detected by reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: The contents of TNF-alpha, IL-6, NO, NOS, MDA, MPO and iNOS mRNA in
      liver homogenate of shock group were increased after transfusion and
      resuscitation, and their levels were higher at 6 and 12 hours. The values were
      significantly higher than those of the sham group, while the activity of SOD was
      significantly lower than that of sham group (P<0.05 or P<0.01). The contents of
      TNF-alpha, IL-6, NO, NOS, MDA, MPO and iNOS mRNA in liver homogenate were lower
      significantly after transfusion and 3, 6, 12 and 24 hours after resuscitation
      than those of shock group at each time points, and the SOD activity was higher
      (P<0.05 or P<0.01). CONCLUSION: The results demonstrate that the ligation of
      mesenteric lymph duct could reduce the polymorphonuclear leucocyte (PMN) detain,
      and its mechanism might relate to reduction of neutrophil aggregation, thus
      decreases the release of TNF-alpha and IL-6, reduces the NO and expression of
      iNOS mRNA, reduces the release of free radicals and consumption of SOD, as a
      result, it reduces the inflammation response of liver in serious hemorrhagic
      shock rats.

PMID- 18611334
TI  - [The expression and function of pulmonary surfactant protein A in severe acute
      pancreatitis in rats].
AB  - OBJECTIVE: To investigate the expression and function of surfactant protein A (SP
      A) in lung in rats with acute lung injury (ALI) induced by severe acute
      pancreatitis (SAP). METHODS: Twenty Sprague-Dawley (SD) rats were randomly
      divided into 2 groups: sham operation group (sham, n=10) and SAP model group
      (SAP, n=10). SAP model was reproduced in SAP group. In sham group laparotomy only
      was done. Serum amylase (AMY) levels, partial pressure of oxygen in artery (PaO2)
      and lung wet/dry (W/D) ratio were determined. SP-A mRNA expression in lung was
      detected by reverse transcription-polymerase chain reaction (RT-PCR). SP-A
      protein expression in lung tissues was assessed by immunohistochemistry. The
      pathologic changes in pancreas and lung were observed 24 hours after reproduction
      of the model. RESULTS: Compared with sham group, PaO(2) in SAP group was
      decreased significantly [(96.78+/-3.81) mm Hg vs. (79.24+/-5.84) mm Hg, 1 mm
      Hg=0.133 kPa, P<0.05]. Serum levels of AMY and W/D ratio in SAP group were
      remarkably higher than that in sham group [(1 193.41+/-192.54) U/L vs. (7
      144.19+/-727.91) U/L, 3.70+/-0.90 vs. 8.57+/-2.45, both P<0.05]. The expression
      of SP-A mRNA in lung tissues in SAP group was significantly down-regulated
      compared with that in sham group (1.21+/-0.10 vs. 0.80+/-0.11, P<0.05). The
      expression of SP-A protein in lung in SAP group was significantly decreased than
      that in sham group (7 982.22+/-3 689.57 vs. 3 497.99+/-2 958.21, P<0.05). The
      pathologic changes in pancreas and lung were marked in SAP group. The expression
      of SP-A protein and mRNA showed significant negative correlation with the extent
      of lung injury (r1= -0.876, P<0.01; r2= -0.713, P<0.05). CONCLUSION: SP-A
      decreases remarkably in ALI induced by SAP. Type II alveolar epithelial cells
      might play an important role in ALI induced by SAP.

PMID- 18611335
TI  - [Effects of liquids with different osmotic pressure and different oxygen
      concentration on resuscitation of hemorrhagic shock at high altitude in rat].
AB  - OBJECTIVE: To compare the effects of liquids with different osmotic pressure and
      different oxygen concentration on resuscitation of hemorrhagic shock at high
      altitude. METHODS: Hemorrhagic shock model of Sprague-Dawley (SD) rats was
      reproduced by Weigger method at the altitude of 3,658 meters. After 1 hour blood
      loss, the rats were treated either with normal saline, 75 g/L hypertonic saline
      solution, 60 g/L dextran 40 solution, solution of 75 g/L hypertonic saline
      solution with 60 g/L dextran 40, or hypertonic sodium chloride hydroxyethyl
      starch 40 solution, and all the above solutions were oxygenated with oxygen by
      high pressure. All the solutions were infused via external jugular vein (4 ml/kg)
      to resuscitate the rats, and the effects of different solutions on blood pressure
      (BP), blood gas, intraventricular pressure, water contents of lung or brain,
      survival time and survival rates were observed. RESULTS: The BP, mean arterial
      pressure (MAP), partial pressure of oxygen in artery (PaO2), left ventricular
      systolic pressures (LVSP), maximum upstroke velocity (+dp/dt max) and maximum
      descending velocity (-dp/dt max) of intraventricular pressure, survival time and
      survival rate were increased (P<0.05 or P<0.01), but the survival time of the
      rats in groups treated with hypertonic solutions or hypertonic colloid solutions
      was obviously prolonged. In particular, survival time and survival rate of the
      rats in the groups treated with hypertonic colloid solutions were raised more
      significantly than those of other groups. Besides, the results showed that BP
      rose steadily in all the groups, PaO2 and LVSP of these groups significantly
      increased, but partial pressure of carbon dioxide in artery (PaCO2) showed no
      significant change. Infusion of 4 ml/kg of liquids did not increase water
      contents of lung or brain. Hyperoxic solutions had no effect on the right
      ventricular pressure, but the oxygenated liquids could lower the right
      ventricular pressure at the beginning of resuscitation, suggesting that oxygen
      transfer through the vein could lower the pulmonary artery pressure and improve
      the right ventricle function. CONCLUSION: Liquids with different osmotic pressure
      and at different oxygen concentration showed therapeutical effect on hemorrhagic
      shock at high altitude in rat, with hypertonic colloid solution being the best
      among the liquids under examination.

PMID- 18611336
TI  - [Cell apoptosis and expression of hypoxia-inducible transcription factor-1 alpha
      in kidney tissue after severe burn with delayed fluid resuscitation in rats in
      areas of different altitude].
AB  - OBJECTIVE: To explore the relationship of cell apoptosis and expression
      regularity of hypoxia-inducible transcription factor (HIF)-1 alpha after severe
      burn with delayed fluid resuscitation in areas of different altitude. METHODS: A
      total of 240 male Wistar rats, which were raised in areas of different altitude
      (1,517 and 3,840 meters), were employed as the experimental models [They received
      a 30% total body surface area (TBSA)III degree scald injury], and then they were
      randomly divided into 3 groups: delayed fluid resuscitation group (DFR, n=50),
      immediate fluid resuscitation group (IFR, n=60) and control group (CG, n=10).
      Renal tissue samples were harvested at 1, 6, 12, 24, 72 and 168 hours after burn,
      respectively. Cell apoptosis was detected by tissue chip technology and terminal
      deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL). The
      expression of HIF-1 alpha was assessed by immunohistochemistry and image
      analysis. RESULTS: With increase in altitude, cellular edema, degeneration,
      necrosis and disintegration of renal tissue were gradually worsening, the
      capillaries of renal glomeruli became dilated and engorged, with degeneration and
      necrosis of endothelial cells, engorgement and edema of renal interstitium, and
      infiltration of inflammatory cells. Pathological changes in DFR group were more
      serious than that of IFR group. Cell apoptosis and the expression of HIF-1 alpha
      were both enhanced, the latter mainly appeared in nuclei of renal cells, and they
      were more marked at 3,840 meters compared with those at 1,517 meters. They were
      more marked in experimental groups than in control group, especially so in DFR
      group (P<0.01). Cell apoptosis was positively correlated with the expression of
      HIF-1 alpha (r= -0.651, P<0.01). CONCLUSION: Severe burn at high attitude plateau
      results in high expression of HIF-1 alpha and an increase in apoptosis of renal
      cells. HIF-1 alpha plays a role in kidney cell apoptosis.

PMID- 18611337
TI  - [Changes in pulmonary transforming growth factor-beta1/smad2 signaling pathway in
      a two-hit pulmonary injury as a result of uncontrolled hemorrhagic shock and
      lipopolysaccharide in rats].
AB  - OBJECTIVE: To investigate the changes in pulmonary transforming growth factor
      beta1 (TGF-beta1)/smad2 signaling pathway in pulmonary injury as a result of
      hemorrhagic shock followed by lipopolysaccharide challenge. METHODS: Twenty-four
      Sprague-Dawley (SD) rats were randomly assigned to the following two groups: sham
      operation group (sham group, surgery, no hemorrhage and no resuscitation), and
      two-hit model group (HS group), each n=12. Three-phased uncontrolled hemorrhagic
      shock model was reproduced in rats. Hemorrhagic shock phase I began with blood
      withdrawal over 15 minutes, i.e. animals were subjected to massive hemorrhage
      [mean arterial pressure (MAP)=35-40 mm Hg (1 mm Hg=0.133 kPa) for 60 minutes],
      followed by intratracheal lipopolysaccharide 2 mg/kg (two-hit model). Ninety
      minutes after blood shedding, resuscitation phase II of 60 minutes began with
      hemostasis, return of all the blood initially shed, plus fluids. Observation
      phase III was 210 minutes. After phase III, blood gas analysis with carotid
      artery blood was performed. Lung tissue was sampled to measure values of wet-to
      dry lung weight (W/D) ratio and pulmonary microvascular permeability.
      Immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR)
      were used to assess the expression of TGF-beta1 protein and mRNA, and the protein
      content of the smad2 was determined by Western blotting. RESULTS: Compared with
      sham group, MAP was significantly lowered after 60 minutes in phase I, and lactic
      acid content was increased significantly, while partial pressure of oxygen in
      artery (PaO2), blood pH, HCO(-)3, arterial oxygen saturation (SaO2) and negative
      base excess (BE) showed a significant decrease in HS group. Concomitantly, values
      of pulmonary microvascular permeability and W/D ratio were significantly
      increased in HS group (all P<0.01). In sham group, weak TGF-beta1 staining was
      detected in the alveolar epithelial cells. However, intense positive
      immunostaining for TGF-beta1 was observed in alveolar epithelial cells, pulmonary
      interstitial inflammatory cell as well as macrophage cells of alveolar space of
      the HS group. Lung tissue in HS group demonstrated a marked increase in TGF-beta1
      mRNA and smad2 protein expression in the lung tissue compared with those of sham
      group (all P<0.01). CONCLUSION: The expression of TGF-beta1/smad2 signaling
      pathway may play an important role in regulation of pulmonary permeability and
      development of pulmonary edema in acute lung injury induced by uncontrolled
      hemorrhagic shock followed by lipopolysaccharide challenge.

PMID- 18611338
TI  - [Comparison of cardiovascular responses between orotracheal and nasotracheal
      intubation with the aid of GlideScope video laryngoscope].
AB  - OBJECTIVE: To compare the cardiovascular responses to orotracheal or nasotracheal
      intubation with the aid of GlideScope video laryngoscope (GSVL). METHODS: Sixty
      patients, American Society of Anesthesiologists (ASA) physical status I, aged 16
      50 years, scheduled for elective plastic surgery under general anesthesia,were
      randomly allocated equally to the orotracheal intubation group (OTI group) and
      the nasotracheal intubation group (NTI group). After the routine anesthesia
      induction, orotracheal and nasotracheal intubation was respectively performed
      with the aid of GSVL. Non-invasive blood pressure and heart rate (HR) were
      recorded before (baseline values) and after anesthesia induction (postinduction
      values), during intubation and every minute for 5 minutes after intubation.
      Maximum values of blood pressure and HR during the observation periods were
      recorded. The product of HR and systolic blood pressure [rate pressure product
      (RPP)] at every time point was calculated. Duration for glottis exposure and
      duration for successful intubation were also noted. RESULTS: There were no
      significant differences between two groups in the demographic data (P>0.05).
      Glottis exposure time and intubation time in NTI group were significantly longer
      than those in OTI group [(52.2+/-13.5) seconds vs. (40.5+/-15.2) seconds,
      P<0.05]. After anesthesia induction, blood pressure and RPP in both groups
      decreased significantly compared with baseline values, but no significant change
      in HR was noted. Compared with their postinduction values, the blood pressure and
      RPP in both groups and HR in OTI group increased significantly at intubation. In
      OTI group,the maximum values of HR, diastolic blood pressure (DBP), mean arterial
      pressure (MAP), RPP exceeded their baseline values. But in NTI group,only maximal
      HR during the observation period was significantly higher than the baseline
      values. The blood pressure at every time point was not significantly different
      between two groups. But intubation in OTI group caused significant increases in
      HR and RPP compared with those in NTI group (both P<0.05). CONCLUSION: In
      anesthetized adult patients, orotracheal and nasotracheal intubations with the
      GSVL can result in a similar pressor response, however orotracheal intubation
      with GSVL causes more marked cardiovascular responses than nasotracheal
      intubation with the aid of GSVL.

PMID- 18611339
TI  - [Study on the value of the formula of rapid synchronous stepwise increase in
      dosage of epinephrine combined with aminophylline (7 mg/kg) in cardiopulmonary
      resuscitation].
AB  - OBJECTIVE: To investigate the effect of application and clinical value of use of
      epinephrine in graduate increased dosage according to the equation G=(K+2n-1)mg/3
      minutes (K=1,2,n=1,2...5,G< or =0.2 mg/kg) combined with aminophylline in
      cardiopulmonary resuscitation (CPR). METHODS: Three hundred and seventy-six
      patients with sudden cardiac arrest(CA) were randomly divided into 3 groups.
      Epinephrine and aminophylline were given through cubital vein with following
      methods: (1)CONTROL: (n=130). 1 mg of adrenaline was given as the first
      treatment. Repeat the same every 3 minutes if there was no effect. (2) In one
      hundred and thirty cases, the first dose of epinephrine was K=1 mg (n=122), K=2
      mg (n=124). In K=1 mg group,epinephrine 1 mg and aminophylline 7 mg/kg were given
      as the first dose. If it was not effective, increasing dosage of epinephrine in
      order of 2, 3...17 mg and aminopyrine 7 mg/kg was given intravenously
      successively every 3 minutes (K=1, 2, n=1, 2...5). In group 2 (group equation 2),
      epinephrine 2 mg and aminophylline 7 mg/kg were given rapidly intravenously. If
      not effective, the drugs were repeated according to the equation intravenously
      every 3 minutes. When the dose of epinephrine exceeded 0.2 mg/kg, it should be
      stopped. Electrocardiogram, mean arterial pressure (MAP), the heart rate (HR),
      and the time of recovery of spontaneous circulation (+ROSC) were monitored, and
      they were evaluated for the effectiveness of resuscitation. RESULTS: (1)+ROSC
      rate (91.13%, 88.52%), the 24-hour survival rate (85.48%, 67.21%), the survival
      rate (49.19%, 31.15%), and the Glasgow coma scores [(13.12+/-1.27)scores,
      (12.28+/-1.32) scores] were all significantly elevated in groups in which
      patients received the modified regime compared with the control group [26.92%,
      25.39%, 12.31% and (9.08+/-1.13) scores, all P<0.01]. The average time for +ROSC
      in the equation 2 and 1 groups was (8.93+/-3.27) minutes and (8.25+/-5.25)
      minutes, respectively, and they were significantly shorter than those of the
      control group [(39.25+/-9.75) minutes, both P<0.01]. (2) The average dose of the
      epinephrine was much reduced in achieving +ROSC in two groups with modified
      regimes as compared with control group [(11.75+/-3.25) mg and (13.85+/-5.15) mg,
      respectively vs. (24.65+/-4.35) mg, both P<0.05], and the number of using
      application epinephrine via intravenous from the CPR initial stage to +ROSC in
      the equation 2 and 1 groups was much significantly decreased compared with the
      control group [(3.45+/-0.55) times and (3.85+/-0.75) times vs. (18.25+/-0.75)
      times, both P<0.01]. CONCLUSION: The newly formed regime has better effects in
      increasing significantly the success rate of cardiac-resuscitation, the survival
      rate, and it also shortens the time for successful recovery of spontaneous
      circulation. It can improve the recovery of brain and nervous system function.

PMID- 18611340
TI  - [Role of nuclear factor-KappaB in endothelial injury in acute myocardial
      infarction].
AB  - OBJECTIVE: To examine the change in nuclear factor-KappaB (NF-KappaB) activity,
      tumor necrosis factor-alpha (TNF-alpha) and soluble thrombomodulin (sTM) levels
      at different time following reperfusion in acute myocardial infarction (AMI), and
      to identify the role of ischemia/reperfusion after ischemia in injury to
      endothelial cells and its relevant mechanism. METHODS: AMI group included 8
      randomly selected patients with AMI, and a normal control group (n=8) composing
      individuals who underwent health check. NF-KappaB activity in monocytes was
      determined by electrophoretic mobility shift assays (EMSA). The level of TNF
      alpha was measured by radio-immunity and sTM was measured by enzyme linked
      immunosorbent assay (ELISA). RESULTS: The NF-KappaB activity, TNF-alpha and sTM
      levels raised dramatically at 0.5 hour after reperfusion, reaching peak at 1 hour
      and declined gradually at 3, 12 and 24 hours. The levels of all the determined
      parameters at every time point were significantly higher than that of normal
      control group, and their levels at 1 hour were significantly higher than that at
      24 hours (all P<0.05). There was a positive correlation between the NF-KappaB
      activity and the levels of TNF-alpha and sTM (all P<0.05). CONCLUSION: These
      results indicate that NF-KappaB is activated and the levels of TNF-alpha and sTM
      rise significantly after reperfusion in AMI. The activation of NF-KappaB maybe
      one of the most important pathogenic mechanism of endothelial injury.

PMID- 18611341
TI  - [Study on safety and efficacy of concentrated potassium chloride infusions in
      critically ill patients with hypokalemia].
AB  - OBJECTIVE: To explore the safety and clinical efficacy of intravenous infusion of
      concentrated potassium chloride using micro-pumps in critically ill patients with
      hypokalemia. METHODS: One hundred and twenty-eight critically ill patients with
      hypokalemia, the endogenous creatinine clearance rate over 0.5 ml/second and the
      urine output over 50 ml/hour were randomly divided into the therapy group (n=64)
      and the control group (n=64). Patients in therapy group received 1,208 mmol/L
      (9%) KCl, while those in the control group received 201 mmol/L (1.5%) potassium
      chloride, intravenously with the aid of a micro-pump, with hourly equal quantity
      of KCl in both groups. Patients in both groups were monitored strictly, and the
      potassium infusion was stopped whenever the serum potassium exceeded or equal to
      3.5 mmol/L. RESULTS: It took (15.55+/-3.22) hours and (14.18+/-4.93) hours for
      the therapy group and the control group to correct the hypokalemia respectively,
      and there was no significant difference (P>0.05). Potassium infusion brought
      larger amount of fluid in the control group than the therapy group [(124.36+/
      25.79) ml vs. (680.83+/-236.70) ml, P<0.01]. All patients tolerated the infusion
      without evidence of hemodynamic change, hyperkalemia or acute heart dysfunction.
      For all the patients, renal function did not throw significant influence on the
      potassium infusion time. An inverse correlation was observed between preinfusion
      potassium concentration and the quantity of potassium infused (r= -0.259,
      P<0.01). CONCLUSION: Under meticulous monitoring, it is safe and effective to
      infuse concentrated potassium for the critically ill patients with hypokalemia.
      This strategy can also be followed in patients with mild renal dysfunction but
      without oliguria or anuria under careful monitoring.

PMID- 18611342
TI  - [The prediction value of modified early warning score grade for death of the
      patients in intensive care unit].
AB  - OBJECTIVE: To study the prediction value and practicality of modified early
      warning score (MEWS) grade for death of the patients in intensive care unit
      (ICU). METHODS: According to the predetermined criteria, the clinical data of
      patients who were admitted to ICU during January 2005 to August 2006(patients
      with ICU stay exceeding 2 hours were enrolled for study) were collected, and MEWS
      grade and acute physiology and chronic evaluation II (APACHE II) scores were
      assessed (90 days as the end point of the observation period). MEWS and APACHE
      II's receiver operator characteristic (ROC) curve, and their predication index
      were calculated and compared. RESULTS: The MEWS's and APACHE II's score in non
      survivors were higher than the survivors. This difference had statistically
      significant difference (both P<0.01). In prediction of death of the patients in
      ICU, the MEWS grade > or =5 scores, Sensitivity was 89.66%, Specificity was
      86.21%, accuracy rating was 87.93%, Youden index (YI)=0.758 6 and area under
      curve (AUC)=0.911 4. However for the APACHE II, they were grade > or =16 scores,
      Sensitivity was 96.55%, Specificity was 79.31%, accuracy rating was 87.93%,
      YI=0.758 6 and AUC=0.898 9. CONCLUSION: MEWS grade is a useful index to predict
      the death of the patients in ICU. It is simple and practical, therefore it should
      be recommended in clinical practice.

PMID- 18611343
TI  - [Effects of fluvastatin on the expression of Janus kinase 2/signal transducers
      and activators of transcription (JAK/STAT) in glomerular mesangial cells under
      high concentration of glucose].
AB  - OBJECTIVE: To investigate the effects of fluvastatin on activation of Janus
      kinase 2 (JAK2) and signal transducers and activators of transcription 1, 3
      (STAT1, 3) in glomerular mesangial cells(GMCs) under high concentration of
      glucose. METHODS: Rat GMCs were cultured in vitro, and they were treated with
      glucose and fluvastatin respectively. Tyrosine phosphorylation of JAK2 (p-JAK2)
      expression was detected by immunoprecipitation and Western blotting analysis. The
      protein expressions of JAK2, STAT1, p-STAT1, STAT3 and p-STAT3 were assessed by
      Western blotting. The protein synthesis of transforming growth factor-beta1 (TGF
      beta1) and fibronectin (FN) in the supernatants of the GMCs were determined by
      enzyme-linked immunoadsorbent assay (ELISA). TGF-beta1 mRNA was assessed by
      reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: Compared
      with low glucose control group, the expressions of p-JAK2 (802+/-124 vs.204+/
      31), p-STAT1 (2,856.6+/-337.8 vs. 617.7+/-76.2), p-STAT3 (3,049.8+/-421.3 vs.
      946.7+/-141.2) and TGF-beta1 mRNA were significantly up-regulated in GMCs under
      high glucose medium, and the concentration of TGF-beta1 in the supernatants
      [(2.87+/-0.34) microg/L vs. (1.20+/-0.11) microg/L] and FN [(6.34+/-0.61) mg/L
      vs. (3.24+/-0.26) mg/L, both P<0.01] were higher in the supernatants. The
      expression levels of p-JAK2 (412+/-67), p-STAT1 (1,178.4+/-137.1), p-STAT3
      (1,572.6+/-181.2) and TGF-beta1 mRNA were significantly lower in fluvastatin
      group than those in high glucose group. The concentration of TGF-beta1 [(1.94+/
      0.27) microg/L] and FN [(4.27+/-0.33)mg/L] in the supernatants in fluvastatin
      group were lower than those in high glucose control group (all P<0.05).
      CONCLUSION: Fluvastatin can inhibit overproduction of TGF-beta1 and FN in GMCs
      under high concentration of glucose, the underlying mechanism may partly be
      attributable to its influence on phosphorylation of JAK/STAT.

PMID- 18611344
TI  - [Effects of glycine on expression of nuclear factor-KappaB and tumor necrosis
      factor-alpha in liver tissue of rats with traumatic shock].

PMID- 18611345
TI  - [A clinical study on cardiopulmonary resuscitation in neonates with different
      modes of closed cardiac massage matched with artificial respiration].

PMID- 18611346
TI  - [The protective effect of high density lipoprotein on renal injury following
      severe burns in rat].

PMID- 18611347
TI  - [Sampling survey on the current situation of human resource in Chinese intensive
      care unit].

PMID- 18611358
TI  - Late-breaking trials at the ACC scientific sessions: insights and controversy.

PMID- 18611359
TI  - Late adverse events after drug-eluting stent implantation.
AB  - Stents that elute antiproliferative drugs prevent restenosis after percutaneous
      coronary artery revascularization, reducing the need for repeat procedures.
      Randomized trials in low-risk patients supported initial regulatory approval for
      drug-eluting stents (DES). In 2006, meta-analyses of long-term outcomes from
      these trials associated DES use with adverse events, believed to be attributable
      to late stent thrombosis, occurring more than 9 months after the initial
      procedure. This article appraises these late adverse effects and illustrates the
      power and shortcomings of large national registries, focused, well-conducted
      clinical trials, and meta-analyses of clinical trial data. This timely, robust
      evidence base reflects an alignment of academic, industry, and public health
      priorities.

PMID- 18611360
TI  - The evolving role of medical therapy for chronic stable angina.
AB  - The management of chronic stable angina has undergone considerable evolution over
      the past two decades. This article highlights the need for a comprehensive
      approach to management that includes carefully identifying cardiac risk factors,
      using therapeutic lifestyle interventions, aggressive, multifaceted medical
      therapy, and judiciously using myocardial revascularization. For patients whose
      ischemia cannot be optimally controlled with traditional anti-ischemic agents, a
      novel antianginal and anti-ischemic agent (ie, ranolazine) has promise in
      reducing refractory ischemia as add-on therapy. This article discusses the role
      of coronary artery bypass graft surgery and percutaneous coronary intervention
      (PCI) in managing chronic stable angina patients and the clinical implications of
      the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive drug
      Evaluation) trial. The combined use of a "focal" approach (PCI to treat the
      culprit stenosis) and a "systemic" approach (lifestyle intervention and
      aggressive pharmacotherapy) may afford the best event-free survival and clinical
      outcomes in patients with stable angina.

PMID- 18611361
TI  - Optimal treatment of the diabetic patient with multivessel disease.
AB  - Diabetes is emerging as a major source of cardiovascular morbidity and mortality.
      The atherosclerosis associated with diabetes has a complex etiology with even
      more complicated manifestations, such as multivessel and diffuse coronary
      disease. The optimal management of the diabetic patient with multivessel disease
      poses a special challenge in terms of the selection of the revascularization
      strategy and medical therapies. In this article, we assess the evidence
      accumulated to date and discuss ongoing studies that will help better inform this
      intricate decision-making process.

PMID- 18611362
TI  - Lessons learned from the CRUSADE National Quality Improvement Initiative.
AB  - The CRUSADE National Quality Improvement Initiative was created to track national
      care patterns, facilitate process improvement, and improve patient outcomes among
      patients with acute coronary syndromes (ACS). CRUSADE found that patients in
      community practice were sicker than those in randomized clinical trials and often
      failed to receive evidence-based therapies. Dosing regimens of antithrombotic
      therapy were also suboptimal, raising safety concerns. Over time, guideline
      adherence and dosing regimens of ACS patients have improved dramatically, leading
      to significantly improved outcomes. Ongoing quality improvement efforts will be
      needed to further improve evidence-based and personalized care of patients with
      ACS.

PMID- 18611364
TI  - Should Prasugrel or Clopidogrel Be Used in Patients with ACS?

PMID- 18611363
TI  - New data on early management of patients with ST-elevation myocardial infarction.
AB  - The advances in the early treatment of ST-segment elevation acute myocardial
      infarction have resulted in a significant reduction in mortality. Early
      pharmacologic therapy with antiplatelet and antithrombotic therapy coupled with
      rapid and complete mechanical or pharmacologic reperfusion has been shown to
      reduce infarct size, improve left ventricular function, and reduce morbidity and
      mortality. Primary angioplasty, if done by an experienced team in a timely
      manner, has been found to be superior to fibrinolytic therapy and superior to
      facilitated angioplasty. The American College of Cardiology/American Heart
      Association guidelines recommend the goal of a door-to-balloon time of less than
      90 minutes. National efforts to reduce delays and to improve access to timely
      therapy will significantly reduce mortality even further.

PMID- 18611365
TI  - Early intervention: which patients and how early?
AB  - Despite advances in preventive therapy, acute coronary syndromes (ACS) remain a
      significant cause of morbidity and mortality. Patient risk varies widely along a
      spectrum from unstable angina to ST-segment elevation myocardial infarctions
      (STEMIs) and can be estimated using risk prediction algorithms. Estimated risk is
      useful to select therapeutic options ranging from aggressive medical therapy for
      patients at low risk to revascularization for high-risk patients in whom bypass
      or percutaneous coronary intervention (PCI) is feasible. Appropriate timing of an
      invasive strategy is crucial, with early intervention maximally benefiting the
      highest-risk patients. Facilitated PCI's role in patients who present with STEMI
      and the most appropriate timing of interventional therapy in patients at moderate
      risk after a non-ST-elevation ACS remain the subject of ongoing debate.

PMID- 18611366
TI  - Which heparin and how much?
AB  - Acute coronary syndromes (ACS) are among the most common presentations to
      emergency departments in North America. An important therapeutic decision facing
      the clinician is whether antithrombotic therapy is justified and which type
      confers the lowest risk:benefit ratio. Using low molecular weight heparin (LMWH)
      has resulted in improved cardiovascular outcomes over unfractionated heparin in
      the noninvasively treated; however, its use as the antithrombotic agent in the
      invasive management of ACS has not always been superior. There have also been
      concerns about bleeding risk with LMWH, especially in the elderly and those with
      impaired renal function. The longer half-life of LMWH and the complexity of
      reversing its effect, in the context of multiple antiplatelet and fibrinolytic
      drugs, have also spurred debate. Finally, there is concern over unwanted
      thrombotic events with these agents in the cardiac catheterization laboratory.

PMID- 18611367
TI  - Sorting through new biomarkers.
AB  - Early diagnosis of acute coronary syndromes (ACS) allows for efficient risk
      stratification, appropriate targeted therapies, and faster patient disposition
      within crowded emergency departments. Although only troponin testing is
      recommended for routine use in the 2007 American College of Cardiology/American
      Heart Association guidelines for non-ST-elevation ACS, emerging data support
      selected use of other biomarkers, including B-type natriuretic peptides (BNPs)
      and C-reactive protein. There remains a need to identify additional biomarkers in
      ACS to enhance risk stratification and to help guide therapeutic decisions in
      this increasingly complex area of cardiovascular medicine. Cardiac biomarkers may
      help to diagnosis ACS before cardiomyocyte necrosis, to influence the decision
      for early invasive treatment, and to provide a means of monitoring response to
      therapy. In this review, we assess new data in ACS with respect to troponins,
      BNPs, myeloperoxidase, fatty acid-binding protein, and monocyte chemoattractant
      protein-1. We also discuss novel biomarkers including growth deficient factor-15
      and neopterin.

PMID- 18611368
TI  - Antiplatelet therapy in acute coronary syndromes.
AB  - Acute coronary syndromes (ACS), characterized by unstable angina or a non-ST
      segment elevation myocardial infarction, are caused by rupture of an
      atherosclerotic plaque, leading to platelet activation and aggregation, thrombus
      formation, and microembolization. Antiplatelet therapy is a cornerstone of
      therapy. Combined with aspirin, clopidogrel provides significant benefit for
      patients across the ACS spectrum. However, clopidogrel has limitations given its
      slow onset and the inconsistent level of inhibition that it achieves. Newer
      thienopyridine and non-thienopyridine P2Y12 receptor agonists offer the
      advantages of a rapid onset of action and greater and more consistent platelet
      inhibition.

PMID- 18611370
TI  - Sus out sugars in.

PMID- 18611369
TI  - Lipid management: considerations in acute coronary syndrome.
AB  - Managing dyslipidemia is an important part of the primary and secondary
      prevention of coronary heart disease. Low-density lipoprotein cholesterol
      reduction remains the primary lipid goal. Patients who have experienced an acute
      coronary syndrome (ACS) are at very high risk of recurrent adverse cardiovascular
      events. A growing body of literature supports the concept that early and
      intensive treatment with statins after an ACS event decreases recurrent adverse
      cardiovascular events. We review available evidence pertaining to lipid
      alterations in ACS.

PMID- 18611371
TI  - DegP: a Protein "Death Star".

PMID- 18611373
TI  - A lipidic-sponge phase screen for membrane protein crystallization.
AB  - A major current deficit in structural biology is the lack of high-resolution
      structures of eukaryotic membrane proteins, many of which are key drug targets
      for the treatment of disease. Numerous eukaryotic membrane proteins require
      specific lipids for their stability and activity, and efforts to crystallize and
      solve the structures of membrane proteins that do not address the issue of lipids
      frequently end in failure rather than success. To help address this problem, we
      have developed a sparse matrix crystallization screen consisting of 48 lipidic
      sponge phase conditions. Sponge phases form liquid lipid bilayer environments
      which are suitable for conventional hanging- and sitting-drop crystallization
      experiments. Using the sponge phase screen, we obtained crystals of several
      different membrane proteins from bacterial and eukaryotic sources. We also
      demonstrate how the screen may be manipulated by incorporating specific lipids
      such as cholesterol; this modification led to crystals being recovered from a
      bacterial photosynthetic core complex.

PMID- 18611372
TI  - Protein-protein interactions in the membrane: sequence, structural, and
      biological motifs.
AB  - Single-span transmembrane (TM) helices have structural and functional roles well
      beyond serving as mere anchors to tether water-soluble domains in the vicinity of
      the membrane. They frequently direct the assembly of protein complexes and
      mediate signal transduction in ways analogous to small modular domains in water
      soluble proteins. This review highlights different sequence and structural motifs
      that direct TM assembly and discusses their roles in diverse biological
      processes. We believe that TM interactions are potential therapeutic targets, as
      evidenced by natural proteins that modulate other TM interactions and recent
      developments in the design of TM-targeting peptides.

PMID- 18611374
TI  - Ab initio folding of proteins with all-atom discrete molecular dynamics.
AB  - Discrete molecular dynamics (DMD) is a rapid sampling method used in protein
      folding and aggregation studies. Until now, DMD was used to perform simulations
      of simplified protein models in conjunction with structure-based force fields.
      Here, we develop an all-atom protein model and a transferable force field
      featuring packing, solvation, and environment-dependent hydrogen bond
      interactions. We performed folding simulations of six small proteins (20-60
      residues) with distinct native structures by the replica exchange method. In all
      cases, native or near-native states were reached in simulations. For three small
      proteins, multiple folding transitions are observed, and the computationally
      characterized thermodynamics are in qualitative agreement with experiments. The
      predictive power of all-atom DMD highlights the importance of environment
      dependent hydrogen bond interactions in modeling protein folding. The developed
      approach can be used for accurate and rapid sampling of conformational spaces of
      proteins and protein-protein complexes and applied to protein engineering and
      design of protein-protein interactions.

PMID- 18611375
TI  - Structural basis for dimerization in DNA recognition by Gal4.
AB  - Gal4 is a Zn2Cys6 binuclear cluster containing transcription factor that binds
      DNA as a homodimer and can activate transcription by interacting with the mutant
      Gal11P protein. Although structures have been reported of the Gal4 dimerization
      domain and the binuclear cluster domain bound to DNA as a dimer, the structure of
      the "complete" Gal4 dimer bound to DNA has not previously been described. Here we
      report the structure of a complete Gal4 dimer bound to DNA and additional
      biochemical studies to address the molecular basis for Gal4 dimerization in DNA
      binding. We find that Gal4 dimerization on DNA is mediated by an intertwined
      helical bundle that deviates significantly from the solution NMR structure of the
      free dimerization domain. Associated biochemical studies show that the
      dimerization domain of Gal4 is important for DNA binding and protein
      thermostability. We also map the interaction surface of the Gal4 dimerization
      domain with Gal11P.

PMID- 18611376
TI  - Crystal structure of the outer membrane protein OpdK from Pseudomonas aeruginosa.
AB  - In Gram-negative bacteria that do not have porins, most water-soluble and small
      molecules are taken up by substrate-specific channels belonging to the OprD
      family. We report here the X-ray crystal structure of OpdK, an OprD family member
      implicated in the uptake of vanillate and related small aromatic acids. The OpdK
      structure reveals a monomeric, 18-stranded beta barrel with a kidney-shaped
      central pore. The OpdK pore constriction is relatively wide for a substrate
      specific channel (approximately 8 A diameter), and it is lined by a positively
      charged patch of arginine residues on one side and an electronegative pocket on
      the opposite side-features likely to be important for substrate selection. Single
      channel electrical recordings of OpdK show binding of vanillate to the channel,
      and they suggest that OpdK forms labile trimers in the outer membrane. Comparison
      of the OpdK structure with that of Pseudomonas aeruginosa OprD provides the first
      qualitative insights into the different substrate specificities of these closely
      related channels.

PMID- 18611378
TI  - Beyond induced-fit receptor-ligand interactions: structural changes that can
      significantly extend bond lifetimes.
AB  - While the lifetime of conventional receptor-ligand interactions is shortened by
      tensile mechanical force, some recently discovered interactions, termed catch
      bonds, can be strengthened by force. Motivated by the search for the underpinning
      structural mechanisms, we here explore the structural dynamics of the binding
      site of the bacterial adhesive protein FimH by molecular dynamics and steered
      molecular dynamics. While the crystal structure of only one FimH conformation has
      been reported so far, we describe two distinctively different conformations of
      the mannose-bound FimH binding site. Force-induced dissociation was slowed when
      the mannose ring rotated such that additional force-bearing hydrogen bonds formed
      with the base of the FimH binding pocket. The lifetime of the complex was further
      enhanced significantly by rigidifying this base. We finally show how even sub
      angstrom spatial alterations of the hydrogen bonding pattern within the base can
      lead to significantly decreased bond lifetimes.

PMID- 18611377
TI  - Analysis of the Staphylococcus aureus DgkB structure reveals a common catalytic
      mechanism for the soluble diacylglycerol kinases.
AB  - Soluble diacylglycerol (DAG) kinases function as regulators of diacylglycerol
      metabolism in cell signaling and intermediary metabolism. We report the structure
      of a DAG kinase, DgkB from Staphylococcus aureus, both as the free enzyme and in
      complex with ADP. The molecule is a tight homodimer, and each monomer comprises
      two domains with the catalytic center located within the interdomain cleft. Two
      distinctive features of DkgB are a structural Mg2+ site and an associated
      Asp*water*Mg2+ network that extends toward the active site locale. Site-directed
      mutagenesis revealed that these features play important roles in the catalytic
      mechanism. The key active site residues and the components of the Asp*water*Mg2+
      network are conserved in the catalytic cores of the mammalian signaling DAG
      kinases, indicating that these enzymes use the same mechanism and have similar
      structures as DgkB.

PMID- 18611379
TI  - Multiple-site trimethylation of ribosomal protein L11 by the PrmA
      methyltransferase.
AB  - Ribosomal protein L11 is a universally conserved component of the large subunit,
      and plays a significant role during initiation, elongation, and termination of
      protein synthesis. In Escherichia coli, the lysine methyltransferase PrmA
      trimethylates the N-terminal alpha-amino group and the epsilon-amino groups of
      Lys3 and Lys39. Here, we report four PrmA-L11 complex structures in different
      orientations with respect to the PrmA active site. Two structures capture the L11
      N-terminal alpha-amino group in the active site in a trimethylated post-catalytic
      state and in a dimethylated state with bound S-adenosyl-L-homocysteine. Two other
      structures show L11 in a catalytic orientation to modify Lys39 and in a
      noncatalytic orientation. The comparison of complex structures in different
      orientations with a minimal substrate recognition complex shows that the binding
      mode remains conserved in all L11 orientations, and that substrate orientation is
      brought about by the unusual interdomain flexibility of PrmA.

PMID- 18611380
TI  - The interplay of functional tuning, drug resistance, and thermodynamic stability
      in the evolution of the M2 proton channel from the influenza A virus.
AB  - We explore the interplay between amino acid sequence, thermodynamic stability,
      and functional fitness in the M2 proton channel of influenza A virus.
      Electrophysiological measurements show that drug-resistant mutations have minimal
      effects on M2's specific activity, and suggest that resistance is achieved by
      altering a binding site within the pore rather than a less direct allosteric
      mechanism. In parallel, we measure the effects of these mutations on the free
      energy of assembling the homotetrameric transmembrane pore from monomeric helices
      in micelles and bilayers. Although there is no simple correlation between the
      evolutionary fitness of the mutants and their stability, all variants formed more
      stable tetramers in bilayers, and the least-fit mutants showed the smallest
      increase in stability upon moving from a micelle to a bilayer environment. We
      speculate that the folding landscape of a micelle is rougher than that of a
      bilayer, and more accommodating of conformational variations in nonoptimized
      mutants.

PMID- 18611381
TI  - Structure of the parathyroid hormone receptor C terminus bound to the G-protein
      dimer Gbeta1gamma2.
AB  - A critical role of the Gbetagamma dimer in heterotrimeric G-protein signaling is
      to facilitate the engagement and activation of the Galpha subunit by cell-surface
      G-protein-coupled receptors. However, high-resolution structural information of
      the connectivity between receptor and the Gbetagamma dimer has not previously
      been available. Here, we describe the structural determinants of Gbeta1gamma2 in
      complex with a C-terminal region of the parathyroid hormone receptor-1 (PTH1R) as
      obtained by X-ray crystallography. The structure reveals that several critical
      residues within PTH1R contact only Gbeta residues located within the outer edge
      of WD1- and WD7-repeat segments of the Gbeta toroid structure. These regions
      encompass a predicted membrane-facing region of Gbeta thought to be oriented in a
      fashion that is accessible to the membrane-spanning receptor. Mutation of key
      receptor contact residues on Gbeta1 leads to a selective loss of function in
      receptor/heterotrimer coupling while preserving Gbeta1gamma2 activation of the
      effector phospholipase-C beta.

PMID- 18611382
TI  - The tRNA-induced conformational activation of human mitochondrial phenylalanyl
      tRNA synthetase.
AB  - All class II aminoacyl-tRNA synthetases (aaRSs) are known to be active as
      functional homodimers, homotetramers, or heterotetramers. However, multimeric
      organization is not a prerequisite for phenylalanylation activity, as monomeric
      mitochondrial phenylalanyl-tRNA synthetase (PheRS) is also active. We herein
      report the structure, at 2.2 A resolution, of a human monomeric mitPheRS
      complexed with Phe-AMP. The smallest known aaRS, which is, in fact, 1/5 of a
      cytoplasmic analog, is a chimera of the catalytic module of the alpha and
      anticodon binding domain (ABD) of the bacterial beta subunit of (alphabeta)2
      PheRS. We demonstrate that the ABD located at the C terminus of mitPheRS overlaps
      with the acceptor stem of phenylalanine transfer RNA (tRNAPhe) if the substrate
      is positioned in a manner similar to that seen in the binary Thermus thermophilus
      complex. Thus, formation of the PheRS-tRNAPhe complex in human mitochondria must
      be accompanied by considerable rearrangement (hinge-type rotation through
      approximately 160 degrees) of the ABD upon tRNA binding.

PMID- 18611384
TI  - The crystal structure of the Ran-Nup153ZnF2 complex: a general Ran docking site
      at the nuclear pore complex.
AB  - Nucleoporin (Nup) 153 is a highly mobile, multifunctional, and essential nuclear
      pore protein. It contains four zinc finger motifs that are thought to be crucial
      for the regulation of transport-receptor/cargo interactions via their binding to
      the small guanine nucleotide binding protein, Ran. We found this interaction to
      be independent of the phoshorylation state of the nucleotide. Ran binds with the
      highest affinity to the second zinc finger motif of Nup153 (Nup153ZnF2). Here we
      present the crystal structure of this complex, revealing a new type of Ran-Ran
      interaction partner interface together with the solution structure of Nup153ZnF2.
      According to our complex structure, Nup153ZnF2 binding to Ran excludes the
      formation of a Ran-importin-beta complex. This finding suggests a local Nup153
      mediated Ran reservoir at the nucleoplasmic distal ring of the nuclear pore,
      where nucleotide exchange may take place in a ternary Nup153-Ran-RCC1 complex, so
      that import complexes are efficiently terminated.

PMID- 18611383
TI  - Starch catabolism by a prominent human gut symbiont is directed by the
      recognition of amylose helices.
AB  - The human gut microbiota performs functions that are not encoded in our Homo
      sapiens genome, including the processing of otherwise undigestible dietary
      polysaccharides. Defining the structures of proteins involved in the import and
      degradation of specific glycans by saccharolytic bacteria complements genomic
      analysis of the nutrient-processing capabilities of gut communities. Here, we
      describe the atomic structure of one such protein, SusD, required for starch
      binding and utilization by Bacteroides thetaiotaomicron, a prominent adaptive
      forager of glycans in the distal human gut microbiota. The binding pocket of this
      unique alpha-helical protein contains an arc of aromatic residues that
      complements the natural helical structure of starch and imposes this conformation
      on bound maltoheptaose. Furthermore, SusD binds cyclic oligosaccharides with
      higher affinity than linear forms. The structures of several SusD/oligosaccharide
      complexes reveal an inherent ligand recognition plasticity dominated by the three
      dimensional conformation of the oligosaccharides rather than specific
      interactions with the composite sugars.

PMID- 18611385
TI  - Single copies of Sec61 and TRAP associate with a nontranslating mammalian
      ribosome.
AB  - During cotranslational protein translocation, the ribosome associates with a
      membrane channel, formed by the Sec61 complex, and recruits the translocon
      associated protein complex (TRAP). Here we report the structure of a ribosome
      channel complex from mammalian endoplasmic reticulum in which the channel has
      been visualized at 11 A resolution. In this complex, single copies of Sec61 and
      TRAP associate with a nontranslating ribosome and this stoichiometry was verified
      by quantitative mass spectrometry. A bilayer-like density surrounds the channel
      and can be attributed to lipid and detergent. The crystal structure of an
      archaeal homolog of the Sec61 complex was then docked into the map. In this
      model, two cytoplasmic loops of Sec61 may interact with RNA helices H6, H7, and
      H50, while the central pore is located below the ribosome tunnel exit. Hence,
      this copy of Sec61 is positioned to capture and translocate the nascent chain.
      Finally, we show that mammalian and bacterial ribosome-channel complexes have
      similar architectures.

PMID- 18611386
TI  - The SNARE complex from yeast is partially unstructured on the membrane.
AB  - Molecular recognition between cognate SNAREs leads to the formation of a four
      helix bundle, which facilitates vesicle docking and membrane fusion. For a SNARE
      system involved in trafficking in yeast, target membrane (t-) SNARE Sso1p and
      vesicle associated (v-) SNARE Snc2p contribute one SNARE motif each, whereas
      another t-SNARE (Sec9) donates two N-terminal and C-terminal SNARE motifs (SN1
      and SN2) to the helical bundle. By use of EPR, it is found that SN2 has a
      tendency to be uncoiled, leaving a significant population of the SNARE complexes
      to be partially unstructured on the membrane. In sharp contrast, SN2 is fully
      engaged in the four-helix bundle when removed from the membrane, showing that the
      membrane is the main destabilizing factor. Helix-breaking proline mutations in
      SN2 did not affect the rate of docking but reduced the rate of lipid mixing
      significantly, indicating that SN2 plays an essential role in activating the
      transition from docking to fusion.

PMID- 18611387
TI  - Observations on the feeding habits of Lutzomyia longipalpis (Lutz & Neiva, 1912)
      (Diptera: Psychodidae: Phlebotominae) in Campo Grande, an endemic area of
      visceral leishmaniasis in Mato Grosso do Sul, Brazil.
AB  - Sand flies were captured weekly with CDC light traps from December 2003 to
      November 2005 in three areas of Campo Grande, in the Brazilian state of Mato
      Grosso do Sul. These areas incorporated two patches of remnant forest and five
      houses. The blood meals of engorged female sand flies were identified using the
      avidin-biotin system of immunoenzymatic ELISA capture. Most (327/355) of the
      females analysed were Lutzomyia longipalpis, of which 66.4% reacted with human
      blood, 64.8% with that of birds and 8.9% with that of dogs. Females that had
      taken human blood predominated in the residential areas and two forest patches.
      The following combinations of blood were also detected for L. longipalpis in some
      of the samples analysed: bird+human (43.4%), bird+human+dog (6.1%). The
      combination bird+human+dog+pig was also found for Nyssomyia whitmani. Dogs and
      pigs appear to have little attractiveness for L. longipalpis. The results
      obtained demonstrate the eclecticism and high anthropophily of L. longipalpis and
      raise new questions with regard to the importance of dogs in VL epidemiology and
      the possible role of man as a source of infection for sand flies.

PMID- 18611388
TI  - Continuous monitoring of restriction endonuclease cleavage activity by universal
      molecular beacon light quenching coupled with real-time polymerase chain
      reaction.
AB  - We describe a method for sensitive monitoring of restriction endonuclease
      kinetics and activity by use of a universal molecular beacon (U-MB) coupled with
      real-time polymerase chain reaction (PCR). The method is used to monitor the
      progress of DNA cleavage in a sealed reaction tube and offers more accurate and
      high-throughput detection. The template has a universal tail hybridized with the
      U-MB and the remaining sequence is complementary to one of the restriction
      endonuclease digestion products. The U-MB is replaced by the extension of
      digested product and the fluorescence quenches. With this concept, one universal
      fluorescence probe can be used in different enzyme analytical systems. In the
      work described here, homogenous assays were performed with the restriction
      endonucleases AluI, EcoRI, XhoI, and SacI at smoothly controlled temperature.
      Cleavage efficiencies were determined, and the potential applications of this
      method were discussed. Furthermore, the AluI and EcoRI cleavage reactions were
      monitored online at varying substrate concentrations at the molecular level, and
      K(m), V(max), and K(cat) values were calculated. The results suggest that U-MB
      monitoring of restriction endonuclease assays based on real-time PCR will be very
      useful for high-throughput, sensitive, and precise assays for enzyme activity
      screening and evolutionary biotechnology analysis.

PMID- 18611389
TI  - A fluorescence polarization assay to quantify biotin and biotin-binding proteins
      in whole plant extracts using Alexa-Fluor 594 biocytin.
AB  - A high-throughput fluorescence polarization assay has been developed for the
      detection of biotin and biotin-binding proteins in whole leaf extracts. Various
      groups are investigating the insecticidal properties of avidin and other biotin
      binding proteins expressed in leaves of transgenic plants. The methods commonly
      used to quantify biotin and avidin in leaf extracts are enzyme-linked
      immunosorbent assay (ELISA) and Western blotting. Here we describe a homogeneous
      fluorescence polarization (FP) method that quantifies transgenic avidin in whole
      leaf extract by the simple addition of the fluorescent avidin ligand Alexa-Fluor
      594 biocytin (AFB). The FP assay exploits the fact that AFB excites and emits in
      regions of the spectrum that are relatively free of background fluorescence in
      leaf extract. Transgenic leaf avidin can be quantified within 1-2 h by the FP
      method, in comparison with 1-2 days for ELISA and Western blotting. The FP method
      can also measure the amount of biotin in control leaves, not expressing avidin.
      Functional avidin levels of 1.54 microM (26.1 microg/g leaf tissue) were detected
      in tobacco leaves expressing vacuole-targeted avidin. Control leaves had biotin
      levels of around 0.74 microM (approximately 0.18 microg/g leaf tissue). Reagent
      costs are minimal: typically AFB is used at concentrations of 1-10 nM, avidin is
      used at 1-100 nM, and sample volumes are 20 microL in 384-well microplates.

PMID- 18611390
TI  - Molecular mechanisms for Kv1.3 potassium channel current inhibition by CD3/CD28
      stimulation in Jurkat T cells.
AB  - In T lymphocyte, activation of Kv1.3 channel, the major voltage-dependent K(+)
      channel, is an essential step for cell proliferation in immune responses. Here,
      effects of anti-CD3 and anti-CD28 antibodies on Kv1.3 current were examined in
      three types of human T lymphocyte derived cell lines, Jurkat E6-1, p56lck-kinase
      deficient mutant JCaM.1, and CD45-phosphatase deficient mutant J45.01. Kv1.3
      current was partly reduced by CD3 stimulation and more strongly by addition of
      anti-CD28 antibody in E6-1. In JCaM.1, Kv1.3 current responses to anti-CD28/CD3
      antibodies were similar to those in E6-1. In J45.01, CD3 stimulation partly
      inhibited Kv1.3 current, but the additive reduction by CD28 stimulation was not
      significant. The inhibition of tyrosine phosphatase in E6-1 abolished the
      additional inhibition by anti-CD28 antibody in a similar manner as in J45.01. In
      conclusion, the stimulation of CD28 in addition to CD3 strongly inhibits Kv1.3
      current and this additive inhibition is mediated by CD45 activation.

PMID- 18611391
TI  - Long-term effects of resveratrol supplementation on suppression of atherogenic
      lesion formation and cholesterol synthesis in apo E-deficient mice.
AB  - Atherosclerosis is a chronic inflammatory disease of the arteries resulting from
      interactions between lipids, monocytes, and arterial wall cells. The effects of
      resveratrol supplements (RV, 0.02% and 0.06% each, w/w) with regard to the
      modulation of lipid profiles, cholesterol synthesis, and anti-atherogenesis were
      examined in apo E-deficient (apo E(-/-)) mice fed a normal diet. The
      concentration of total-cholesterol (total-C) and LDL-cholesterol (LDL-C) in
      plasma was significantly lower in the resveratrol-supplemented groups compare to
      the control group over the entire experimental period. The plasma HDL-C
      concentration was significantly elevated, and the ratio of HDL-C/total-C was
      significantly higher in the CF and RV groups than in the control group. Plasma
      paraoxonase (PON) activity was significantly higher in the 0.06% resveratrol
      group. The hepatic HMG-CoA reductase (HMGR) activity was significantly lower in
      the clofibrate and resveratrol groups than in the control group. Resveratrol
      supplements attenuated the presence of atherosclerotic lesions and periarterial
      fat deposition in the apo E(-/-) mice. The presence of intracellular adhesion
      molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in
      atherosclerotic vessels was diminished in the resveratrol-supplemented apo E(-/-)
      mice. These results provide new insight into the anti-atherogenic and
      hypocholesterolemic properties of resveratrol in apo E(-/-) mice that were fed a
      normal diet.

PMID- 18611392
TI  - Stathmin-like 2, a developmentally-associated neuronal marker, is expressed and
      modulated during osteogenesis of human mesenchymal stem cells.
AB  - Stathmin-like 2 (STMN2) protein, a neuronal protein of the stathmin family, has
      been implicated in the microtubule regulatory network as a crucial element of
      cytoskeletal regulation. Herein, we describe that STMN2 expression increases at
      both mRNA and protein levels during osteogenesis of human mesenchymal stem cells
      derived from adipose tissue (hMADS cells) and bone marrow (hBMS cells), whereas
      it decreases to undetectable levels during adipogenesis. STMN2 protein is
      localized in both Golgi and cytosolic compartments. Its expression appears
      modulated in osteoblasts by nerve growth factor, dexamethasone or RhoA kinase
      inhibitor Y-27632 which are known effectors of osteogenesis. Thus STMN2 appears a
      novel marker of osteogenesis and osteoblast per se, that could play a role in the
      regulation of the adipocyte/osteoblast balance.

PMID- 18611393
TI  - Synergistic action of gastrin and ghrelin on gastric acid secretion in rats.
AB  - Gastrin and ghrelin are secreted from G cells and X/A-like cells in the stomach,
      respectively, and respective hormones stimulate gastric acid secretion by acting
      through histamine and the vagus nerve. In this study, we examined the
      relationship between gastrin, ghrelin and gastric acid secretion in rats.
      Intravenous (iv) administration of 3 and 10 nmol of gastrin induced transient
      increases of ghrelin levels within 10 min in a dose-dependent manner. Double
      immunostaining for ghrelin and gastrin receptor revealed that a proportion of
      ghrelin cells possess gastrin receptors. Although (iv) administration of gastrin
      or ghrelin induced significant gastric acid secretion, simultaneous treatment
      with both hormones resulted in a synergistic, rather than additive, increase of
      gastric acid secretion. This synergistic increase was not observed in vagotomized
      rats. These results suggest that gastrin may directly stimulate ghrelin release
      from the stomach, and that both hormones may increase gastric acid secretion
      synergistically.

PMID- 18611394
TI  - Characterisation of the in vitro activity of the depsipeptide histone deacetylase
      inhibitor spiruchostatin A.
AB  - We recently completed the total synthesis of spiruchostatin A, a depsipeptide
      natural product with close structural similarities to FK228, a histone
      deacetylase (HDAC) inhibitor (HDI) currently being evaluated in clinical trials
      for cancer. Here we report a detailed characterisation of the in vitro activity
      of spiruchostatin A. Spiruchostatin A was a potent (sub-nM) inhibitor of class I
      HDAC activity in vitro and acted as a prodrug, requiring reduction for activity.
      Spiruchostatin A was a potent (low nM) inhibitor of the growth of various cancer
      cell lines. Spiruchostatin A-induced acetylation of specific lysine residues
      within histones H3 and H4, and increased the expression of p21(cip1/waf1), but
      did not induce acetylation of alpha-tubulin. Spiruchostatin A also induced cell
      cycle arrest, differentiation and cell death in MCF7 breast cancer cells. Like
      FK228, spiruchostatin A was both an inducer and substrate of the ABCB1 drug
      efflux pump. Whereas spiruchostatin A and FK228-induced protracted histone
      acetylation, hydroxamate HDI-induced short-lived histone acetylation. Using a
      subset of HDI-target genes identified by microarray analysis, we demonstrated
      that these differences in kinetics of histone acetylation between HDI correlated
      with differences in the kinetics of induction or repression of specific target
      genes. Our results demonstrate that spiruchostatin A is a potent inhibitor of
      class I HDACs and anti-cancer agent. Differences in the kinetics of action of HDI
      may be important for the clinical application of these compounds.

PMID- 18611395
TI  - The monoterpenoids citral and geraniol are moderate inhibitors of CYP2B6
      hydroxylase activity.
AB  - Monoterpenes are found in the volatile essence of flowers, plants oils, and
      herbal medicines. Some are commonly used as food additives and fragrance
      components, and many are found in cosmetics, soaps, cleaning products,
      disinfectants, preservatives, and medicines. We have recently discovered a
      moderate inhibitory effect of borneol and isoborneol toward CYP2B6-catalyzed
      bupropion hydroxylase activity. Based on that result, we expanded our study to
      evaluate the inhibitory effects of 22 monoterpenoids on CYP2B6 activity in vitro.
      Among the monoterpenoids screened, borneol, camphor, cineole, isoborneol,
      menthol, and perillaldehyde showed slight inhibition of CYP2B6-catalyzed
      bupropion hydroxylation, displaying greater than 50% inhibition at 50muM. Citral
      and geraniol strongly inhibited CYP2B6 hydroxylase activity in a competitive
      manner, with K(i) values of 6.8 and 10.3muM, respectively, which are higher than
      the K(i) (1.8muM) of the well-known CYP2B6-selective inhibitor thio-TEPA. These
      in vitro data indicate that high amounts of these two monoterpenoids might
      interact with drugs that are metabolized by CYP2B6. The in vivo pharmacokinetics
      of these compounds should be examined to determine whether the inhibition of
      CYP2B6 activity by monoterpenoids has clinical relevance.

PMID- 18611396
TI  - Reconsideration of hydrophobic lipid distributions in lipoprotein particles.
AB  - Lipoprotein particles are commonly known as micellar aggregates with hydrophobic
      lipids located within the core and amphipathic molecules in the surface. Using a
      new structural model for optimizing the distribution of hydrophobic lipids,
      namely triglyceride (TG) and cholesterol ester (CE) molecules, we reveal that
      particle size-dependent proportion of these 'core lipids' may locate in the
      surface of lipoprotein particles. The composition of the particles also strongly
      influences the actual molecular content of the surface. For example, in high
      density lipoprotein (HDL) particles the percentage of CEs of all surface lipids
      is between 13% and 27% due to the high tendency of CEs to locate in the surface
      and the high concentration of CEs in the particles. Conversely, although the
      percentage of TG molecules in the surface of HDL particles is also high,
      approximately 60% as for CE, the percentage of TGs of all surface lipids is low,
      only up to 5%, because HDL particles have a low-TG concentration. These
      structural models provide an intuitive and coherent structural rationale for
      various metabolic cascades in lipoprotein metabolism with the catalytic enzyme
      action and molecular binding for transport proteins taking place at the surface
      of the particles.

PMID- 18611397
TI  - Endothelin receptor antagonist CPU0213 and vitamin E reverse downregulation of
      FKBP12.6 and SERCA2a: a role of hyperphosphorylation of PKCepsilon.
AB  - Downregulation of FKBP12.6 and sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a)
      contributes to sudden cardiac death and heart failure. We aimed to test the
      hypothesis that (i) downregulation of FKBP12.6 and SERCA2a can be taken as
      molecular markers for drug interventions and (ii) such downregulation is produced
      by crosstalk between endothelin-reactive oxygen species and beta-adrenoceptors
      stimulation, mediated by hyperphosphorylation of protein kinase Cvarepsilon
      (PKCvarepsilon). Rat cardiomyocytes were incubated with isoproterenol (1 microM),
      endothelin-1 (0.1 microM) or hydrogen peroxide (10 microM) for 18 h, resulting in
      downregulation of mRNA and protein of FKBP12.6 and SERCA2a, as well as
      upregulation of PKCvarepsilon mRNA and phosphorylated PKCvarepsilon protein.
      These changes were reversed by an application of either propranolol (1 microM),
      endothelin receptor antagonist CPU0213 (1 microM) or vitamin E (1 microM). As
      indicated by the fluorescent dye Fluo3, diastolic [Ca(2+)](i) in rat ventricular
      myocytes was increased after incubation with isoproterenol (0.1 microM). The
      increased [Ca(2+)](i) in diastole was dramatically decreased by CPU0213. Thus,
      the downregulation of FKBP12.6 and SERCA2a, and hyperphosphorylation of
      PKCvarepsilon, appear to be related to crosstalk between over-activated
      endothelin-reactive oxygen species and a beta-adrenoceptor pathway. CPU0213 is
      beneficial in treating cardiac insufficiency and preventing cardiac arrhythmias
      possibly by normalizing hyperphosphorylation of PKCvarepsilon and abnormal
      FKBP12.6 and SERCA2a. The antioxidant activity of vitamin E was sufficient to
      normalize the levels of FKBP12.6 and SERCA2a and phosphorylation of
      PKCvarepsilon. Thus by testing with biomarkers FKBP12.6 and SERCA2a, we have
      shown that the endothelin receptor antagonist CPU0213 and the antioxidant vitamin
      E may relieve risk of lethal arrhythmias and heart failure by suppressing
      PKCvarepsilon.

PMID- 18611398
TI  - Catechin and proanthocyanidin B4 from grape seeds prevent doxorubicin-induced
      toxicity in cardiomyocytes.
AB  - The clinical use of doxorubicin, a highly active anticancer drug, is limited by
      its severe cardiotoxic side effects. Grape seed extract has been reported to
      exert protective effects on doxorubicin-induced cardiotoxicity. The
      cardiovascular protective effects of grape seed extract are believed to be
      ascribed to its antioxidative properties. A series of studies have has
      demonstrated that polyphenols are instrumental for the antioxidative properties
      of grape seed extract. This study was designed to investigate whether two major
      polyphenols isolated from grape seed extract, catechin and proanthocyanidin B4
      (Pc B(4)), had protective effects against doxorubicin-induced toxicity in
      cardiomyocytes and their underlying mechanisms. The results showed that grape
      seed polyphenols catechin and Pc B(4) pretreatment would protect cardiomyocytes
      against doxorubicin-induced toxicity by decreasing reactive oxygen species
      generation as well as the number of apoptotic cells, preventing DNA
      fragmentation, regulating the expression levels of the pro-apoptotic protein Bax
      alpha and the anti-apoptotic protein Bcl-2, and inhibiting apoptotic signaling
      pathways.

PMID- 18611400
TI  - Therapeutic potential of 20(S)-ginsenoside Rg(3) against streptozotocin-induced
      diabetic renal damage in rats.
AB  - The inhibitors of advanced glycation endproduct and oxidative stress, as well as
      N-methyl-d-aspartate (NMDA) receptor antagonists have received considerable
      interest because of their close association with renoprotective effects. The
      therapeutic potential of 20(S)-ginsenoside Rg(3) (20(S)-Rg(3)), isolated from
      Panax ginseng, against streptozotocin-induced diabetic renal damage, was
      investigated in this study. The diabetic rats received 5, 10, and 20 mg/kg body
      weight/day of 20(S)-Rg(3) orally via gavage for fifteen consecutive days. The
      physiological abnormalities such as increases in water intake and urine volume of
      diabetic rats were significantly decreased by the 20 mg/kg body weight of 20(S)
      Rg(3) administration. The elevated serum glucose, glycosylated protein, and
      thiobarbituric acid-reactive substance levels in diabetic rats were also
      significantly reduced by the 20(S)-Rg(3) administrations. Moreover, the renal
      dysfunction of diabetic rats was significantly ameliorated by the 20(S)-Rg(3)
      administrations in a dose-dependent manner. These beneficial effects on diabetic
      renal damage were related to the inhibitory effect of 20(S)-Rg(3) against NMDA
      receptor-mediated nitrosative stress.

PMID- 18611402
TI  - An isometric virus of the potato tuber moth Tecia solanivora (Povolny)
      (Lepidoptera: Gelechiidae) has a tri-segmented RNA genome.
AB  - A small isometric virus has been isolated from larvae of the Guatemala potato
      tuber moth, Tecia solanivora (Povolny), collected in Ecuador. It was designated
      the Anchilibi virus (AnchV). The non-enveloped viral particles have an estimated
      diameter of 32+/-2 nm. Three major proteins were found in virions, with estimated
      sizes of 102.0+/-2.1, 95.8+/-2.0 and 92.4+/-1.5 kDa for AnchV as determined by
      polyacrylamide gel electrophoresis. After denaturing agarose gel electrophoresis,
      the genome of AnchV appeared to be a tri-segmented single-stranded RNA with
      fragment sizes of 4.1+/-0.2, 2.8+/-0.2 and 1.65+/-0.2 kb. In addition to a high
      virulence towards its original host, AnchV also caused high mortality in larvae
      of two other potato tuber moth species, Phthorimaea operculella (Zeller) and
      Symmetrischema (tangolias) plaesiosema (Turner). Electron microscopy confirmed
      that AnchV replication occurs in the cell cytoplasm, mainly in vesicles. Several
      important characteristics exhibited by this virus differ from those reported for
      known families of insect viruses. Thus, AnchV might be member of a new taxonomic
      group.

PMID- 18611401
TI  - Role of Ca(2+) mobilization in desensitization of beta-adrenoceptors by platelet
      derived growth factor in airway smooth muscle.
AB  - Platelet-derived growth factor (PDGF), which is released from eosinophils and
      fibroblasts, may be implicated in the pathophysiology of bronchial asthma. To
      examine the involvement of airway inflammation in beta-adrenergic
      desensitization, the present study was designed to determine whether pre-exposure
      to PDGF deteriorates beta-adrenoceptor function in airway smooth muscle. We
      focused on Ca(2+) signaling as an intracellular mechanism involved in this
      phenomenon. Isometric tension and F(340)/F(380) (an indicator of intracellular
      Ca(2+) concentration) induced by isoprenaline and other cAMP-related agents were
      simultaneously measured before and after exposure to PDGF in fura-2-loaded guinea
      pig tracheal smooth muscle. Indomethacin was applied throughout the experiments
      to abolish prostaglandin synthesis by PDGF. After exposure of the tissues to 10
      ng/ml PDGF for 15 min, the effects of isoprenaline, a beta-adrenoceptor agonist,
      and forskolin, a direct inhibitor of adenylyl cyclase, against methacholine
      induced contraction were markedly reduced with increasing F(340)/F(380). However,
      in the presence of verapamil, an inhibitor of voltage-dependent Ca(2+) channels,
      the reduced responsiveness to isoprenaline and forskolin induced by pre-exposure
      to PDGF was reversed with reducing F(340)/F(380). Reduced responsiveness to
      isoprenaline by PDGF was also not observed in the presence of Ca(2+)-free
      solution. The inhibitory effects of db-cAMP, an analogue of cAMP, and
      theophylline, a nonselective inhibitor of phosphodiesterase, were not attenuated
      by PDGF. In conclusion, pre-exposure to PDGF causes impairment of the beta
      adrenoceptors/adenylyl cyclase processes in airway smooth muscle that is
      independent of cyclooxygenase synthesis by PDGF. Ca(2+) mobilization by Ca(2+)
      influx through voltage-dependent Ca(2+) channels is involved in this heterologous
      desensitization of beta-adrenoceptors.

PMID- 18611399
TI  - Ethanol induces stronger dopamine release in nucleus accumbens (shell) of alcohol
      preferring (bibulous) than in alcohol-avoiding (abstainer) rats.
AB  - Several studies on the differences between ethanol-preferring versus non
      preferring rat lines suggest an innate deficit in the mesolimbic dopaminergic
      system as an underlying factor for ethanol volition. Rats would try to overcome
      such deficit by engaging in a drug-seeking behaviour, when available, to drink an
      ethanol solution over water. Thus, in the present study we compared the effect of
      a single dose of ethanol (1 g/kg, i.p.) on the extracellular levels of monoamines
      measured by microdialysis in the shell of nucleus accumbens of University of
      Chile bibulous (UChB) and University of Chile Abstainer (UChA) rats, bred for 79
      and 88 generations to prefer or reject ethanol, respectively. It is reported that
      under basal conditions extracellular dopamine levels are lower in the bibulous
      than in the abstainer rats, while ethanol induced a 2-fold greater increase of
      dopamine release in bibulous than in abstainer rats. The greater effect of
      ethanol in bibulous rats was not associated to differences in blood ethanol
      levels, since the concentration and elimination of ethanol were virtually
      identical in both rat lines, indicating that bibulous rats are more sensitive to
      the stimulation of dopamine release by ethanol than abstainer rats. No
      differences were observed in 5-hydroxytryptamine or metabolites measured
      simultaneously under basal or ethanol-stimulating conditions in bibulous and
      abstainer rats. Overall, the present results suggest that a low dopaminergic tone
      and a strong mesolimbic dopamine response to ethanol are concerted neurochemical
      features associated to an ethanol-seeking behaviour in rats.

PMID- 18611403
TI  - Infection characteristics of Solenopsis invicta virus 2 in the red imported fire
      ant, Solenopsis invicta.
AB  - Solenopsis invicta virus 2 (SINV-2) is the second virus identified from the fire
      ant, S. invicta Buren. SINV-2 is unique among positive-strand RNA viruses from
      insects by possessing four cistrons in a monopartite genome. Fire ant colonies
      testing positive for SINV-2 by RT-PCR did not exhibit any discernable symptoms.
      RT-PCR-based surveys for SINV-2 among 688 fire ant mounds in Alachua County,
      Florida, sampled during the period January, 2006 through December, 2007 showed
      that the prevalence of SINV-2 among nests ranged from 1.6% to 16.4%. Unlike S.
      invicta virus 1, no seasonal-associated prevalence was observed with regard to
      SINV-2 infection among fire ant colonies. No social form specificity was evident;
      SINV-2 was found in both monogyne and polygyne S. invicta ants. Real-time
      quantitative PCR experiments showed that SINV-2 genome equivalents per individual
      ant ranged from 1.9x10(7)in. pupae to 4.3x10(11)in. inseminated queens. The SINV
      2 infection was detected in all ant stages examined (eggs, larvae, pupae,
      workers, and queens). Tissue tropism studies indicated that the alimentary canal
      (specifically the midgut) is most likely the susceptible tissue. SINV-2 was
      successfully transmitted to uninfected S. invicta ants by feeding a partially
      purified homogenate of SINV-2-infected ants. The SINV-2 transmission rate ranged
      from 30% to 80%, and both positive (genomic) and negative (replicative) SINV-2
      RNA strands accumulated in recipient ants over the course of the experiment.
      These results indicated that SINV-2 replicates within S. invicta.

PMID- 18611404
TI  - Using Bayesian multinomial classifier to predict whether a given protein sequence
      is intrinsically disordered.
AB  - Intrinsically disordered proteins (IDPs) lack a well-defined three-dimensional
      structure under physiological conditions. Intrinsic disorder is a common
      phenomenon, particularly in multicellular eukaryotes, and is responsible for
      important protein functions including regulation and signaling. Many disease
      related proteins are likely to be intrinsically disordered or to have disordered
      regions. In this paper, a new predictor model based on the Bayesian
      classification methodology is introduced to predict for a given protein or
      protein region if it is intrinsically disordered or ordered using only its
      primary sequence. The method allows to incorporate length-dependent amino acid
      compositional differences of disordered regions by including separate statistical
      representations for short, middle and long disordered regions. The predictor was
      trained on the constructed data set of protein regions with known structural
      properties. In a Jack-knife test, the predictor achieved the sensitivity of 89.2%
      for disordered and 81.4% for ordered regions. Our method outperformed several
      reported predictors when evaluated on the previously published data set of
      Prilusky et al. [2005. FoldIndex: a simple tool to predict whether a given
      protein sequence is intrinsically unfolded. Bioinformatics 21 (16), 3435-3438].
      Further strength of our approach is the ease of implementation.

PMID- 18611405
TI  - Aromatization of androstenedione and 16alpha-hydroxyandrostenedione in human
      placental microsomes. Kinetic analysis of inhibition by the 19-oxygenated and 3
      deoxy analogs.
AB  - Inhibition of aromatase activity in human placental microsomes with
      androstenedione (AD) (1a) and its 19-oxygenated derivatives 1b and 1c, their
      16alpha-hydroxy compounds 2 and 3, and 3-deoxyandrost-4-ene compounds 5 and 6 was
      studied using [1beta-(3)H]AD as a substrate and compared to that with [1beta
      (3)H]16alpha-hydroxyandrostenedione (16-OHAD). AD series of steroids, compounds
      1, inhibited competitively [1beta-(3)H]AD aromatization whereas other 16alpha
      hydroxy steroids 2, 3, 5, and 6 inhibited AD aromatization in a non-competitive
      manner. On the other hand, all of 16-OHAD series, compounds 2, blocked the [1beta
      (3)H]16-OHAD aromatization in a competitive manner whereas the AD series steroids
      1 as well as the 3-deoxy-16alpha-hydroxy-17-one steroids 5 and 3-deoxy
      16alpha,17beta-diol steroids 6 inhibited 16-OHAD aromatization non-competitively.
      3-carbonyl and 16alpha-hydroxy functions of 16-OHAD play a critical role of
      selection of the 16-OHAD binding site. The results suggest that the AD
      derivatives 1 are kinetically aromatized at a different site from the 16-OHAD
      derivatives 2. Physical and/or chemical environments around the aromatase protein
      in the microsomal membrane may play a significant role in the expression of the
      substrate specificity, and the present results do not exclude the idea that the
      placental microsomes have a single binding site.

PMID- 18611406
TI  - Delay of selective attention during the attentional blink.
AB  - The attentional blink is the inability to report the second of two targets in an
      RSVP stream when they are separated by 200-500 ms. Recent evidence shows that
      this failure results from three dissociable changes to the properties of temporal
      selective attention. During the attentional blink, selection is suppressed (items
      are selected less effectively, resulting in greater levels of random guessing),
      diffused (more letters around the target are selected), and delayed (the items
      that are selected tend to be later in the RSVP stream relative to the cue) [Vul,
      E., Nieuwenstein, M., & Kanwisher, N. (2008). Temporal selection is suppressed,
      delayed, and diffused during the attentional blink. Psychological Science, 19(1),
      55-61]. Here we assess the properties of the delay in selection and evaluate how
      the delay contributes to the attentional blink. First, by pre-cueing, we
      manipulate the delay of selective attention and show that neither delay nor
      suppression alone is sufficient to account for the failure to report the second
      target; thus both play a role in the usual attentional blink. Second, we explore
      the persistence of the delay effect over much longer T1-T2 SOAs and show that the
      effect remains strong at lags of 1,400 ms and appears to subside with a time
      constant of roughly 500 ms. Third, we manipulate RSVP rate and find that the
      "delay" of selection is a delay in time, independent of the number of items.

PMID- 18611407
TI  - Within-texture collinearity improves human texture segmentation.
AB  - Spatial arrangement has been shown to facilitate both detection of a threshold
      target by collinear flankers and detection of smooth chains within random arrays
      of suprathreshold elements. Here, we investigate the effect of alignment between
      texture elements on orientation-based texture segmentation. Textures composed of
      Gabor elements were used in a figure-discrimination task. The degree of
      collinearity within the texture was manipulated, and threshold figure-ground
      orientation differences found. A facilitative effect of collinearity on
      segmentation was seen, which was insensitive to Gabor carrier phase at the
      texture-element co-axial spacing of 3lambda used here. The pattern of results
      with respect to collinearity could not be attributed simply to improved linkage
      of local orientation contrast at figure borders in isolation, and instead
      suggests a role for the figure interior in texture segmentation.

PMID- 18611409
TI  - Molecular characterization of a cryptic plasmid from the psychrotrophic antarctic
      bacterium Pseudoalteromonas sp. 643A.
AB  - We report the identification and nucleotide sequence analysis of pKW1, a plasmid
      of the psychrotrophic bacterium Pseudoalteromonas sp. 643A isolated from the
      stomach of Antarctic krill Euphasia superba. pKW1 consists of 4583 bp, has a G+C
      content of 43% and seven putative open reading frames (ORFs). The deduced amino
      acid sequence from ORF-1 shared significant similarity with the plasmid replicase
      protein of Psychrobacter cryohalolentis, strain K5. The DNA region immediately
      downstream of the ORF-1 showed some homology with the Rep-binding sequence of the
      theta-replicating ColE2-type plasmids. The ORF-3 amino acid sequence revealed
      amino acid sequence homology with the mobilization protein of Psychrobacter sp.
      PRwf-1 and Moraxella catarrhalis, with identities of 28% and 25%, respectively.
      The ORF-4 showed 46% amino acid sequence homology with the putative
      relaxase/mobilization nuclease MobA of Hafnia alvei and 44% homology with the
      putative mobilization protein A of Pasterulla multocida. The copy number of pKW1
      in Pseudoalteromonas sp. 643A was estimated of 15 copies per chromosome.

PMID- 18611408
TI  - Differential effects of repeated low dose treatment with the cannabinoid agonist
      WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain.
AB  - Pain due to bone malignancies is one of the most difficult types of cancer pain
      to fully control and may further decrease the patients' quality of life. Animal
      models of chronic pain conditions resulting from peripheral inflammatory
      reactions or nerve injuries are responsive to treatment with cannabinoid
      agonists. However, the use of cannabinoid agonists in humans may be hampered by
      CNS related side effects and development of tolerance. In the present study, we
      investigated the effect of repeated low dose administration of the synthetic
      cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in
      mice. In addition, we investigated the development of CNS related side effects
      and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related
      behavior and expression of spinal glial fibrillary acidic protein in the bone
      cancer pain model but not in the neuropathic pain model. Furthermore, this
      treatment strategy was not found to induce measurable CNS related side effects or
      tolerance. Cancer cell viability assays and bone volume fraction assessed by
      micro computed tomography (microCT) demonstrated that these effects were not due
      to changes in cancer progression. The difference in WIN 55,212-2 efficacy between
      the bone cancer and neuropathic pain models may reflect the different pain
      generating mechanisms, which may be utilized in designing new therapeutic drugs.

PMID- 18611410
TI  - l-Glutamate in Middlebrook 7H9 culture medium upregulates matrix
      metalloproteinase-2 secretion from human astrocytoma cells.
AB  - Matrix metalloproteinases (MMPs) are implicated in the pathology of CNS
      tuberculosis. Whilst investigating the secretion of MMP-2 from human U373-MG
      astrocytoma cells, we observed elevated MMP-2 secretion in response to
      Middlebrook 7H9 media but not to Mycobacterium tuberculosis itself. Middlebrook
      7H9 media did not stimulate MMP-1 or MMP-9 secretion from astrocytoma cells. The
      excitatory neurotransmitter l-glutamate, at concentrations found in Middlebrook
      7H9 media, induced significant astrocytoma MMP-2 secretion (p<0.05). l-Glutamate
      induced MMP-2 activity may contribute to neuropathology in various CNS diseases
      and may generate misleading data in pathogen studies where Middlebrook 7H9 is the
      culture medium.

PMID- 18611411
TI  - Development and application of a one-step real-time Taqman RT-PCR assay for
      detection of Duck hepatitis virus type1.
AB  - A one-step real-time RT-PCR assay (rRT-PCR) was developed for efficient detection
      of Duck hepatitis virus type1 (DHV-1). A pair of specific primers was designed
      against the conserved region in the 3D gene that encodes the RNA dependent RNA
      polymerase with a single conserved TaqMan probe. The detection limit of this
      assay was 10 viral genomic copies per reaction and it was highly specific to DHV
      1. The rRT-PCR assay was used to determine the distribution and concentration of
      DHV-1 virulent strain in duck embryos as well as the DHV-1 attenuated vaccine
      strain in chicken embryos. The results revealed that the copy numbers of DHV-1
      reached a peak in duck embryos and chicken embryos at 28-40h, 44-56h
      postinoculation respectively. The comparative tests for ducklings infected
      artificially and clinical samples between neutralization test and rRT-PCR showed
      that the positive results of infected samples were the same, while the rRT-PCR
      method was more sensitive than neutralization test for detection of clinical
      samples. The rapid, sensitive and specific rRT-PCR assay will be a powerful tool
      for detection of suspected cases of DHV-1, distribution pattern of DHV-1 in vivo
      and molecular epidemiological screening.

PMID- 18611412
TI  - Prokaryotic expression of truncated VP7 of bluetongue virus (BTV) and reactivity
      of the purified recombinant protein with all BTV type-specific sera.
AB  - Purification of bluetongue virus (BTV) group-specific VP7 protein, expressed in
      prokaryotic system as histidine-tagged fusion protein is described in the present
      study. The major antigenic portion of VP7 gene of BTV 23 was amplified from the
      extracted RNA by reverse transcription polymerase chain reaction and cloned. The
      recombinant expression construct (pET-VP7) was identified by the polymerase chain
      reaction and sequencing analysis. Expression of histidine-tagged fusion truncated
      VP7 protein with a molecular mass of 36 kDa was determined by Western blot
      analysis using anti-His antibody. The expressed VP7 was purified to near
      homogeneity by chromatography on nickel-agarose column as judged by sodium
      dodesyl sulfate-polyacrylamide gel electrophoresis analysis. The purified VP7
      protein was recognized by antibody to BTV in Western blot analysis. The
      capability of the recombinant VP7 protein to differentiate hyperimmune serum of
      rabbit to BTV from normal rabbit serum was evident in the enzyme-linked
      immunosorbent assay (ELISA). The purified VP7 reacted well with the 24 BTV
      serotype-specific sera obtained from OIE Reference Laboratory on bluetongue. Our
      results indicated that the expressed VP7 protein could be used as antigen for
      development of antibody-capture ELISA for detection BTV group-specific
      antibodies. This recombinant protein may also be used as antigen in competitive
      ELISA format.

PMID- 18611413
TI  - The flavivirus polymerase as a target for drug discovery.
AB  - Flaviviruses are emerging pathogens of increasingly important public health
      concern in the world. For most flaviviruses such as dengue virus (DENV) and West
      Nile virus (WNV) neither vaccine nor antiviral treatment is available. The viral
      RNA-dependent RNA polymerase (RdRp) non-structural protein 5 (NS5) has no
      equivalent in the host cell and is essential for viral replication. Here, we give
      an overview of the current knowledge regarding Flavivirus RdRp function and
      structure as it represents an attractive target for drug design. Flavivirus RdRp
      exhibits primer-independent activity, thus initiating RNA synthesis de novo.
      Following initiation, a conformational change must occur to allow the elongation
      process. Structure-function studies of Flavivirus RdRp are now facilitated by the
      crystal structures of DENV (serotype 3) and WNV RdRp domains. Both adopt a
      classic viral RdRp fold and present a closed pre-initiation conformation. The so
      called priming loop is thought to provide the initiation platform stabilizing the
      de novo initiation complex. A zinc-ion binding site at the hinge between two
      subdomains might be involved in opening up the RdRp structure towards a
      conformation for elongation. Using two different programs we predicted common
      potential allosteric inhibitor binding sites on both structures. We also review
      ongoing approaches of in vitro and cell-based screening programs aiming at the
      discovery of nucleosidic and non-nucleosidic inhibitors targeting Flavivirus
      RdRps.

PMID- 18611414
TI  - Adamantane resistance in influenza A(H1) viruses increased in 2007 in South East
      Asia but decreased in Australia and some other countries.
AB  - The adamantanes (amantadine and rimantadine) were the initial antivirals licensed
      for use against influenza A viruses and have been used in some countries to
      control seasonal influenza and have also been stockpiled for potential pandemic
      use. While high rates of resistance have been observed in recent years with A(H3)
      viruses, the rates of resistance with A(H1) viruses has varied widely. In this
      study we analysed 281 human influenza A viruses isolated in 2007 that were
      referred to the WHO Collaborating Centre for Reference and Research in Melbourne,
      mainly from Australia and the surrounding regions, for evidence of resistance to
      adamantanes and a subset of these was examined for resistance to the
      neuraminidase inhibitors (NIs). We found that the rates of adamantane resistance
      in A(H3) viruses continued to increase in most countries in 2007 but a distinct
      variation was seen with A(H1) resistance levels. A(H1) viruses from Australia,
      New Zealand and Europe had low rates of resistance (2-9%) whereas viruses from a
      number of South East (SE) Asian countries had high rates of resistance (33-100%).
      This difference can be attributed to the spread of A/Brisbane/59/2007-like
      viruses to many parts of the world with the exception of SE Asia where A/Hong
      Kong/2652/2006-like viruses continue to predominate. When these two A(H1)
      subgroups were compared for their in vitro sensitivity to the other class of
      influenza antiviral drugs, the neuraminidase inhibitors, no difference was seen
      between the groups with both showing normal levels of sensitivity to these drugs,
      The finding of reducing A(H1) resistance rates in Australia and rising levels in
      SE Asia in 2007, reverses the trend seen in 2006 when A(H1) resistance levels
      were rising in Australia and elsewhere but remained low in most of SE Asia.

PMID- 18611415
TI  - Early deficits in motor coordination and cognitive dysfunction in a mouse model
      of the neurodegenerative lysosomal storage disorder, Sandhoff disease.
AB  - Mouse models of lysosomal storage diseases, including Sandhoff disease, are
      frequently employed to test therapies directed at the central nervous system. We
      backbred such mice and conducted a behavioral test battery which included
      sensorimotor and cognitive assessments. This is the first report of short-term
      memory deficits in a murine model of Sandhoff disease. We also document early
      onset of motor deficits using the balance beam test.

PMID- 18611416
TI  - Dose dependence and therapeutic window for the neuroprotective effects of
      curcumin in thromboembolic model of rat.
AB  - Curcumin (diferuloylmethane), an active ingredient of turmeric, obtained from the
      powdered rhizomes of Curcuma longa Linn., has been traditionally recognized for
      treatment of several diseases. To evaluate the potential clinical use of
      curcumin, we determined the dose dependence of its effects in the therapeutic
      window and of the neuroprotective efficacy in a cerebral thromboembolic model of
      the rat. Rats were subjected to occlusion of the middle cerebral artery (MCAo) by
      a thrombus and treated with different doses of curcumin or the vehicle at 4h
      after ischemia. The animals were assessed after 24h for motor performance and
      neurological deficit. The rats were sacrificed immediately afterwards for
      evaluation of infarct, edema volume, estimation of nitrate and nitrite levels,
      neutrophil infiltration and levels of GSH and glutathione peroxidase (GSH-Px) in
      brain tissue. Curcumin reduced in a dose-dependent manner the ischemia-induced
      cerebral infarct and edema volume and attenuated neurological deficits observed
      after 24h. Curcumin reduced post-ischemic brain neutrophil infiltration, nitrate
      and nitrite levels and ameliorated the loss of GSH-Px and tends to increase the
      GSH levels but not significantly in the brain tissue. Neuronal levels of reactive
      oxygen species, peroxynitrite, and nitric oxide were lowered and in brain
      cryosections inducible nitric oxide synthase expression were significantly
      inhibited after treatment with curcumin. The present study is the first evidence
      of effectiveness of curcumin when given 4h post-ischemia in the rat
      thromboembolic stroke models, as it reduces infarct volume, ameliorates the
      sensory motor function and significantly attenuated the nitrosative stress.

PMID- 18611417
TI  - Cocaine withdrawal enhances pentobarbital-induced sleep in rats: evidence of
      GABAergic modulation.
AB  - We intended to clarify whether pentobarbital-induced sleep in rats is affected
      during cocaine withdrawal and whether GABAergic systems are involved in this
      sleep. Cocaine (20mg/kg) was administered subcutaneously (s.c.) to rats once per
      day for 6 days. Pentobarbital (42mg/kg) was administered intraperitoneally (i.p.)
      to the rats 1 day (acute withdrawal), 8 days (subacute withdrawal), or 14 days
      (subchronic withdrawal) after withdrawal from cocaine. All rats were fasted for
      24h prior to the pentobarbital injection. Pentobarbital-induced sleeping time was
      significantly increased during both acute and subacute withdrawal, while sleeping
      onset latency was not affected. However, sleeping time recovered to normal 14
      days after withdrawal. Protein levels of GABAA receptor gamma-subunits and
      glutamic acid decarboxylase (GAD) were increased in both acute and subacute
      cocaine withdrawal in the hypothalamus, but were normal after 14 days of
      withdrawal. These results indicate that pentobarbital-induced sleeping time in
      cocaine withdrawal is transiently increased. Hypersomnia in cocaine withdrawal
      might be influenced by functional changes in the GABAergic systems.

PMID- 18611418
TI  - Chitinase is stored and secreted from the inner body of microfilariae and has a
      role in exsheathment in the parasitic nematode Brugia malayi.
AB  - Chitinase expression in microfilariae of the parasitic nematode Brugia malayi (B.
      malayi, Bm) is coincidental with the onset of their infectivity to mosquitoes. An
      antibody raised to Onchocerca volvulus (O. volvulus, Ov) infective-stage larval
      chitinase (Ov-CHI-1) was specifically reactive against B. malayi microfilarial
      chitinase and was used to study the localization of chitinase in B. malayi during
      microfilarial development and transmission to the insect vector. Immuno-electron
      microscopy (IEM) was used to demonstrate that the chitinase was confined to the
      inner body of the microfilariae and furthermore that chitinase was only present
      in sheathed microfilarial species, although the inner body is present in all
      species. Observation using the IEM implicates two distinct routes of chitinase
      secretion from the inner body, via either the pharyngeal thread, or during
      transmission of the microfilariae to the vector, contained in vesicle-like
      structures. Many morphological studies have described the structure of the inner
      body, but no function has been assigned to it as of yet. Although it has been
      commented that the cells surrounding the inner body and pharyngeal thread are
      those destined to become the intestine and pharynx and that the inner body
      represents a store of material. Our studies suggest that chitinase is one such
      product stored in the inner body and that it is secreted during the exsheathment
      of the microfilaria in the mosquito.

PMID- 18611419
TI  - Taxonomic composition and gene content of a methane-producing microbial community
      isolated from a biogas reactor.
AB  - A total community DNA sample from an agricultural biogas reactor continuously fed
      with maize silage, green rye, and small proportions of chicken manure has
      recently been sequenced using massively parallel pyrosequencing. In this study,
      the sample was computationally characterized without a prior assembly step,
      providing quantitative insights into the taxonomic composition and gene content
      of the underlying microbial community. Clostridiales from the phylum Firmicutes
      is the most prevalent phylogenetic order, Methanomicrobiales are dominant among
      methanogenic archaea. An analysis of Operational Taxonomic Units (OTUs) revealed
      that the entire microbial community is only partially covered by the sequenced
      sample, despite that estimates suggest only a moderate overall diversity of the
      community. Furthermore, the results strongly indicate that archaea related to the
      genus Methanoculleus, using CO2 as electron acceptor and H2 as electron donor,
      are the main producers of methane in the analyzed biogas reactor sample. A
      phylogenetic analysis of glycosyl hydrolase protein families suggests that
      Clostridia play an important role in the digestion of polysaccharides and
      oligosaccharides. Finally, the results unveiled that most of the organisms
      constituting the sample are still unexplored.

PMID- 18611420
TI  - The fibroblast growth factor homolog of Bombyx mori nucleopolyhedrovirus enhances
      systemic virus propagation in B. mori larvae.
AB  - All lepidopteran baculovirus genomes sequenced to date encode a viral fibroblast
      growth factor homolog (vFGF). Recently, we generated a Bombyx mori
      nucleopolyhedrovirus (BmNPV) mutant lacking functional vfgf and found that BmNPV
      vfgf contributes to virus virulence in B. mori larvae. However, the steps at
      which BmNPV vFGF works during in vivo virus infection were unclear. To uncover
      the role of vFGF during systemic infection of silkworm larvae, we generated a
      BmNPV mutant, BmIEGFP, possessing an ie-1 promoter-driven green fluorescent
      protein gene, and its derivative BmIEGFP/FGFD, in which vfgf was partially
      deleted from the genome of BmIEGFP. Intrahemocoelic and oral infection
      experiments using these viruses revealed that the loss of functional vFGF reduces
      viral infectivity in B. mori hemocytes. Our results suggest that BmNPV vFGF is
      required for efficient systemic infection, presumably by a chemotactic effect
      that allows budded virus to infect hemocytes efficiently.

PMID- 18611421
TI  - Do in situ forming PLG/NMP implants behave similar in vitro and in vivo? A non
      invasive and quantitative EPR investigation on the mechanisms of the implant
      formation process.
AB  - Electron paramagnetic resonance (EPR) spectroscopy was applied to monitor non
      invasively the formation of in situ forming implants in vitro and in vivo after
      the administration of poly(lactide-co-glycolide) (PLGA)/N-methyl-pyrrolidone
      (NMP) solutions. The nitroxide spin probe 4-benzoyloxy-2,2,6,6
      tetramethylpiperidine-1-oxyl (TB) was incorporated in polymer solutions and
      samples were incubated in 0.1 M phosphate buffer (pH 7.4) at 37 degrees C or
      injected subcutaneously in the femoral of BALB/c mice. EPR permitted the direct
      and continuous determination of the NMP-water exchange during implant formation
      both in vitro and in living mice. The formation of the implant structure followed
      a two phase mechanism: over 75% of the polymer precipitated immediately after
      injection within the first 30 min and formed a solid shell. The subsequent
      moderate solidification of the implants was governed by diffusion and was
      completed after 24 h. The replacement of the organic solvent NMP by water was
      determined by polarity shifts within the implant and could be quantified. Both
      the kinetic of NMP-water exchange and polymer precipitation showed good in vitro
      in vivo correlation.

PMID- 18611422
TI  - Safety and efficacy of live attenuated influenza vaccine in children 2-7 years of
      age.
AB  - Three pivotal trials supported the licensure of live attenuated influenza vaccine
      (LAIV) for children > or =2 years of age: 2 placebo-controlled studies each
      conducted over 2 seasons, and a 1-year trial comparing LAIV with trivalent
      inactivated influenza vaccine (TIV). Analyses were conducted to evaluate the
      safety and efficacy of LAIV in the subgroup of children > or =2 years of age from
      these trials. Efficacy was demonstrated compared with placebo in children aged 2
      7 years in seasons with matched strains (69.2% [95% CI: 52.7, 80.4] and 94.6%
      [95% CI: 88.6, 97.5]), seasons with primarily mismatched strains (87% [95% CI:
      77.0, 92.6]), and during late season epidemics (73.8% [95% CI: 40.4, 89.4]).
      Compared with TIV recipients, LAIV recipients aged 2-5 years had 52.5% (95% CI:
      26.7, 68.7) and 54.4% (95% CI: 41.8, 64.5) fewer cases of influenza illness
      against matched and mismatched strains, respectively. No unusual or unexpected
      adverse reactions were noted. The adverse reactions most commonly associated with
      LAIV were runny nose/nasal congestion and low-grade fever. Hospitalizations and
      medically significant wheezing were increased in children 6-11 and 6-23 months of
      age who received LAIV, respectively, but were not increased in children 2-5 years
      of age.

PMID- 18611423
TI  - Establishing objective detection limits for the pepsin digestion assay used in
      the assessment of genetically modified foods.
AB  - RATIONALE: Guidelines for assessing the potential allergenicity of genetically
      modified (GM) organisms recommend testing the digestibility of the introduced
      protein by pepsin. Previous studies detailed the digestion procedure but have not
      described a simple objective measurement of the extent of digestion nor evaluated
      the impact of variation in pepsin activity. METHODS: Samples of eight proteins
      were digested by pepsin at pH 1.2 and 2.0 using standard conditions (10,000 U of
      pepsin activity per mg test protein) as well as 5000 and 20,000 units per mg of
      test protein. An independent digestion assay of hemoglobin was used to verify
      pepsin activity for each assay. Digestion was stopped in timed samples between
      0.5 and 60 min. Digestion samples and undigested protein (10% and 100%) were
      separated by SDS-PAGE. Residual stained protein bands were measured by image
      analysis. RESULTS: The differences in pH and pepsin concentration only had minor
      effects on digestion of intermediately stable proteins: concanavalin A,
      ovalbumin, and lysozyme, but not on rapidly digested or stable proteins.
      CONCLUSIONS: Verification of pepsin activity and measurement of an objective
      endpoint of digestion (e.g. (90%) should provide more comparable results for the
      safety assessment of novel food proteins.

PMID- 18611424
TI  - Diphenyl diselenide reverses gastric lesions in rats: Involvement of oxidative
      stress.
AB  - The aim of the present study was to evaluate if diphenyl diselenide administered
      by oral route was effective in restoring gastric lesions induced by ethanol. The
      possible involvement of oxidative stress in diphenyl diselenide antiulcer effect
      was also evaluated. Different doses of diphenyl diselenide (dissolved in soya
      bean oil, 1mL/kg) were administered orally 1h before (pre-treatment study) or 1h
      after ethanol (70%, v/v, 2mL/kg, post-treatment study). Ulcer lesions were
      quantified 1h after ethanol administration (pre-treatment protocol) or 1h after
      diphenyl diselenide study (post-treatment protocol). Diphenyl diselenide (0.1
      10mg/kg or 0.32-32micromol/kg), when administered previously or posteriorly
      prevented and reversed respectively, the development of gastric lesions induced
      by ethanol in rats. A number of markers of oxidative stress were examined in rat
      stomach including thiobarbituric acid reactive species (TBARS), catalase (CAT),
      superoxide dismutase (SOD), non-protein thiol groups (NPSH) and ascorbic acid. In
      addition to attenuating the gastric lesions, low doses of diphenyl diselenide
      prevented (pre-treatment) or reversed (post-treatment) the ethanol-induced
      changes in TBARS, SOD activity and ascorbic acid content. In conclusion, the
      present data reveal that diphenyl diselenide, administered by oral route,
      possesses an antiulcer effect by modulating antioxidant mechanisms.

PMID- 18611425
TI  - Protective effect of captopril and enalaprilat, angiotensin-converting enzyme
      inhibitors, on para-nonylphenol-induced *OH generation and dopamine efflux in rat
      striatum.
AB  - We recently reported that para-nonylphenol, an environmental chemical, induced
      hydroxyl radical (*OH) formation in rat striatum. In this study we examined the
      antioxidant effects of angiotensin-converting enzyme inhibitors (captopril or
      enalaprilat) on para-nonylphenol (nonylphenol) and 1-methyl-4-phenylpyridinium
      ion (MPP(+))-induced hydroxyl radical (*OH) formation and dopamine (DA) efflux in
      extracellular fluid of rat striatum, using a microdialysis technique. para
      Nonylphenol clearly enhanced *OH formation and DA efflux induced by MPP(+). When
      captopril or enalaprilat was infused in nonylphenol and MPP(+)-treated rats, DA
      efflux and OH formation significantly decreased, as compared with that in the
      nonylphenol and MPP(+)-treated control. We compared the ability of non-SH
      containing enalaprilat with a SH-containing captopril to scavenge OH and DA
      efflux. Both inhibitors were able to scavenge *OH and DA efflux induced by para
      nonylphenol and MPP(+). The results suggest that angiotensin-converting enzyme
      inhibitors may protect against nonylphenol and MPP(+)-induced *OH formation via
      suppressing DA efflux in the rat striatum.

PMID- 18611426
TI  - Pathological baroreceptor sensitivity in patients suffering from somatization
      disorders: do they correlate with symptoms?
AB  - AIM: We conducted a study to investigate whether patients with somatization
      disorders (ICD-10, F45.0) show abnormal values in autonomic testing. METHOD: 35
      patients with a diagnosis of somatization disorder (SP) were matched to 35
      healthy volunteers (HV). International standardized autonomic testing based on
      heart rate variation and continuously measured blood pressure signals was used to
      assess autonomic activity and establish baroreceptor sensitivity (BRS). Three
      different statistical procedures were used to confirm the reliability of the
      findings. RESULTS: There were no statistical differences between the 2 groups in
      age, BMI, systolic and diastolic blood pressures, and spectral values (total
      power, low, and high frequency power). However, heart rate was higher (p=0.044)
      and baroreceptor sensitivity was lower (p=0.002) in the patients compared to the
      healthy volunteers. Median BRS (+/-S.E.M.) of patients was 9.09+/-0.65 compared
      to 12.04+/-0.94 ms/mmHg in healthy volunteers. Twenty-two of the 35 patients had
      a BRS of -1.0S.D. below the mean of HV. SP with lower values differed from SP
      with normal BRS in values of total power, low-, mid-, and high-frequency bands
      (p<0.01 to <0.0001). No differences in psychometric testing were found between
      patients with lower or higher BRS. In addition, no correlation whatsoever was
      found in relation to autonomic variables between HV and SP, except for a higher
      LF/HF quotient in the latter (p<0.05). CONCLUSION: Autonomic regulation was
      impaired in 62% of patients with a somatization disorder. Severity of clinical
      symptoms measured by psychometric instruments did not preclude autonomic function
      impairment. Accordingly, autonomic dysfunction may constitute an independent
      somatic factor in this patient group.

PMID- 18611427
TI  - 'Extremotaxis': computing with a bacterial-inspired algorithm.
AB  - We present a general-purpose optimization algorithm inspired by "run-and-tumble",
      the biased random walk chemotactic swimming strategy used by the bacterium
      Escherichia coli to locate regions of high nutrient concentration The method uses
      particles (corresponding to bacteria) that swim through the variable space
      (corresponding to the attractant concentration profile). By constantly performing
      temporal comparisons, the particles drift towards the minimum or maximum of the
      function of interest. We illustrate the use of our method with four examples. We
      also present a discrete version of the algorithm. The new algorithm is expected
      to be useful in combinatorial optimization problems involving many variables,
      where the functional landscape is apparently stochastic and has local minima, but
      preserves some derivative structure at intermediate scales.

PMID- 18611428
TI  - Algebraic properties of automata associated to Petri nets and applications to
      computation in biological systems.
AB  - Biochemical and genetic regulatory networks are often modeled by Petri nets. We
      study the algebraic structure of the computations carried out by Petri nets from
      the viewpoint of algebraic automata theory. Petri nets comprise a formalized
      graphical modeling language, often used to describe computation occurring within
      biochemical and genetic regulatory networks, but the semantics may be interpreted
      in different ways in the realm of automata. Therefore, there are several
      different ways to turn a Petri net into a state-transition automaton. Here, we
      systematically investigate different conversion methods and describe cases where
      they may yield radically different algebraic structures. We focus on the
      existence of group components of the corresponding transformation semigroups, as
      these reflect symmetries of the computation occurring within the biological
      system under study. Results are illustrated by applications to the Petri net
      modelling of intermediary metabolism. Petri nets with inhibition are shown to be
      computationally rich, regardless of the particular interpretation method. Along
      these lines we provide a mathematical argument suggesting a reason for the
      apparent all-pervasiveness of inhibitory connections in living systems.

PMID- 18611429
TI  - Modeling the fitness of plant morphologies across three levels of complexity.
AB  - Linking together disparate biological models has the potential to provide
      insights that cannot be gained from studying the models in isolation.
      Computational modeling provides the means to integrate and test theories that
      span different temporal and spatial scales, and thus provides an ideal platform
      for forging this link. This paper describes a model that combines three key
      levels of biological theory. A computational model of gene regulation is
      integrated with a model of early land plant morphology, and placed in an
      evolutionary environment of competing fitness pressures. Simulation results
      indicate that each of these sub-models constrain possible phenotypic fitness.
      This work provides a methodological scaffold upon which increasingly complex
      models at each level of genotype, phenotype and environment can be built.

PMID- 18611430
TI  - Bio-inspired self-organizing cellular systems.
AB  - Bio-inspiration borrows three properties characteristic of living organisms:
      multicellular architecture, cellular division, and cellular differentiation.
      Implemented in silicon according to these properties, our self-organizing systems
      are able to grow, to self-replicate, and to self-repair. The growth and branching
      processes, performed by the so-called Tom Thumb algorithm, lead thus to the
      configuration and cloning mechanisms of the systems. The repair processes allow
      its cicatrization and regeneration mechanisms. The cellular design and hardware
      implementation of these mechanisms constitute the core of this paper.

PMID- 18611431
TI  - Do motifs reflect evolved function?--No convergent evolution of genetic
      regulatory network subgraph topologies.
AB  - Methods that analyse the topological structure of networks have recently become
      quite popular. Whether motifs (subgraph patterns that occur more often than in
      randomized networks) have specific functions as elementary computational circuits
      has been cause for debate. As the question is difficult to resolve with currently
      available biological data, we approach the issue using networks that abstractly
      model natural genetic regulatory networks (GRNs) which are evolved to show
      dynamical behaviors. Specifically one group of networks was evolved to be capable
      of exhibiting two different behaviors ("differentiation") in contrast to a group
      with a single target behavior. In both groups we find motif distribution
      differences within the groups to be larger than differences between them,
      indicating that evolutionary niches (target functions) do not necessarily mold
      network structure uniquely. These results show that variability operators can
      have a stronger influence on network topologies than selection pressures,
      especially when many topologies can create similar dynamics. Moreover, analysis
      of motif functional relevance by lesioning did not suggest that motifs were of
      greater importance to the functioning of the network than arbitrary subgraph
      patterns. Only when drastically restricting network size, so that one motif
      corresponds to a whole functionally evolved network, was preference for
      particular connection patterns found. This suggests that in non-restricted,
      bigger networks, entanglement with the rest of the network hinders topological
      subgraph analysis.

PMID- 18611432
TI  - The AMP-regulated kinase family: enigmatic targets for diabetes therapy.
AB  - AMP-activated protein kinase (AMPK) is a widely conserved Ser/Thr-specific
      protein kinase, homologous to Saccharomyces cerevisiae Snf1, and involved in
      nutrient sensing in lower organisms. In 2003, we reviewed the role of this enzyme
      in glucose homeostasis in mammals [Rutter, G.A., daSilvaXavier, G., Leclerc, I.,
      2003. Roles of 5'-AMP-activated protein kinase (AMPK) in mammalian glucose
      homoeostasis. Biochem. J. 375 (Pt 1), 1-16]. In the subsequent 5 years, dramatic
      strides have taken place in our understanding of the role of AMPK in the control
      of whole body metabolic homeostasis, the regulation of the enzyme by upstream
      kinases, and its molecular structure. These new studies and earlier work arguably
      propel AMPK, and perhaps related family members into a "super league" of
      potential therapeutic targets for maladies including diabetes, cancer, heart
      disease, and obesity. Here, we survey some of these recent advances, focussing on
      the role of this and related enzymes in the control of pancreatic beta-cell
      function and glucose homeostasis.

PMID- 18611434
TI  - Changes in the amounts of myelin lipids and molecular species of plasmalogen PE
      in the brain of an autopsy case with D-bifunctional protein deficiency.
AB  - Changes in the molecular species of lipids associated with peroxisomal d
      bifunctional protein (d-BP) deficiency were investigated in cerebral tissues to
      elucidate the pathological mechanisms underlying this disorder. Total
      phospholipids in the gray and white matters of the patient's brain were decreased
      to approximately 73% and 50% of control levels, respectively, and profound
      declines in myelin lipids, i.e. galactosyl ceramide and sulfatides, indicated
      dysmyelination in our patient with d-BP deficiency. Although the total
      ganglioside amounts in the gray and white matter of this patient's brain were
      also decreased to 61% and 37% of control levels and GM1 in the white matter was
      20% of the control level, the relative amounts of GM2 in both the gray and the
      white matter of this patient's brain were increased in comparison to those in the
      control, indicating altered metabolism of gangliosides. In addition, among
      molecular species of phospholipids, plasmalogen-type and polyunsaturated fatty
      acid-containing phosphatidylethanolamine were characteristically decreased in the
      patient's gray matter. These alterations in the molecular species of brain lipids
      may affect sensitivity to oxidative stress and the membrane fluidity of neural
      cells, thereby producing the brain pathology of d-BP deficiency.

PMID- 18611433
TI  - Hormonal regulation of cardiac KCNE2 gene expression.
AB  - The KCNE2 gene encodes a single transmembrane domain protein that modulates a
      variety of K+ channel functions in various tissues. Here we show that cardiac
      KCNE2 transcript levels are approximately 10-fold upregulated at the end of
      pregnancy. This upregulation was mimicked by 17-beta estradiol but not by 5alpha
      dihydrotestosterone treatments in ovariectomized mice. To investigate the
      mechanism of KCNE2 transcriptional regulation by estrogen, we experimentally
      identified KCNE2 transcription start sites, delineated its gene structure and
      characterized its promoter region. Estrogen treatment stimulated KCNE2 promoter
      activity in a dose-dependent manner and ICI 182,780 blocked estrogen stimulation.
      A direct genomic mechanism was demonstrated by (i) the loss of estrogen
      responsiveness in the presence of a DNA-binding domain mutant estrogen receptor
      alpha or mutant KCNE2 ERE and (ii) binding of ERalpha to the KCNE2 ERE. These
      findings show that a genomic mechanism of estrogen action alters KCNE2
      expression, which may have important physiological implications.

PMID- 18611435
TI  - Solid microemulsion preconcentrate (NanOsorb) of artemether for effective
      treatment of malaria.
AB  - A microemulsion preconcentrate was formulated on the basis of solubility of
      artemether (ARM) in the various oily phases and surfactants and phase diagrams.
      Various solid adsorbents were evaluated for their ability yield solid
      microemulsion preconcentrates (NanOsorb-ARM). NanOsorb-ARM on dilution yielded
      microemulsion with average globule size of 183 nm and polydispersity index of
      0.498 when determined using photon correlation spectroscopy. The antimalarial
      activity of NanOsorb-ARM, ARM solution and marketed ARM formulation (Larither)
      was evaluated in Plasmodium berghei infected mice as per Peter's four day
      protocol. The acute lethal dose and the subacute toxicity of NanOsorb-ARM were
      determined as per the method suggested in Organization for Economic Cooperation
      and Development (OECD) guidelines. The NanOsorb-ARM exhibited significantly
      higher antimalarial activity (P<0.05) as compared to the marketed formulation of
      artemether (Larither). Surprisingly, placebo NanOsorb also showed significantly
      higher antimalarial activity as compared to Larither indicating that excipients
      used for the formulation of NanOsorb may have antimalarial activity. Subacute
      toxicity studies demonstrated that NanOsorb-ARM is comparatively safer than
      artemether oily solution with respect to survival, gross pathology, hematology
      and serum biochemistry in mice of both the genders.

PMID- 18611436
TI  - Nestin-positive cells in the spinal cord: a potential source of neural stem
      cells.
AB  - Some literatures have reported neural precursor cells (NPCs) exist in spinal cord
      of adult mammal, however, the NPCs distribution feature in spinal cord of adult
      mice so far is not described in detail. In order to observe and compare the
      distribution feature of NPCs in various spinal cord regions of adult mice, to
      research a potential source of neural stem cells (NSCs), we obtained NPCs
      distribution feature by analyzing the distribution of the nestin-containing cells
      (NCCs) in spinal cord of adult nestin second-intron enhancer controlled LacZ
      reporter transgenic mice (pNes-Tg) with LacZ staining and positive cell
      quantification. The results showed that: NCCs were observed in various regions of
      spinal cord of adult mice, but amount of NCCs was different in distinct region,
      the rank order of NCCs amount in various spinal cord regions was dorsal horn
      region greater than central canal greater than the ventral and lateral horn. NCCs
      in dorsal horn region mainly distributed in substantia gelatinosa, NCCs in
      central canal mainly distributed in ependymal zone, on the contrary, NCCs in
      ventral, lateral horn, medullae, nucleus regions of spinal cord were
      comparatively less. The rank order of NCCs amount in various spinal cord segments
      was cervical segment greater than lumbar sacral segment greater than thoracic
      segment. There was no significantly difference between NCCs amount in the left
      and right sides, and within cervical 1-7, thoracic 1-12, lumbar 1-5, sacral
      segment of spinal cord in adult mice. These data collectively indicate that NPCs
      extensively distribute in various regions of spinal cord of adult mice,
      especially in substantia gelatinosa and ependymal zone. NPCs in cervical segment
      are abundant, NPCs in thoracic segment are the least while compared the different
      spinal cord segment, the NPCs in various regions of spinal cord of adult mice are
      a potential source of NSCs.

PMID- 18611437
TI  - Vesicular glutamate transporter 3-immunoreactive pericellular baskets ensheath a
      distinct population of neurons in the lateral septum.
AB  - The lateral septum (LS) plays a role in the adjustment of behavioral responses
      according to environmental demands. This is a complex integrative process wherein
      a variety of modulatory systems, i.e. cholinergic, dopaminergic and serotonergic
      projections forming pericellular baskets around LS neurons, are involved.
      Recently, vesicular glutamate transporter 3 (VGLUT3)-immunoreactive (-ir)
      structures outlining unlabeled somata and their proximal dendrites were described
      in the LS. However, the vesicular transporters for acetylcholine and GABA were
      not or only rarely co-expressed with VGLUT3. In this study, the morphology and
      distribution of these VGLUT3-ir structures were systematically analyzed revealing
      that (1) they form distinct pericellular baskets (PBs) displaying variable
      shapes, (2) they are arranged in a layer-like pattern similar to the terminals of
      other modulatory systems, (3) beside a few exceptions (e.g., choline
      acetyltransferase), they are generally not or very sparsely co-localized with
      other neurochemical markers characterizing major neuron populations or afferent
      systems of the LS, i.e. calcium-binding proteins, tyrosine hydroxylase,
      tryptophan hydroxylase, vesicular glutamate transporters 1 (VGLUT1) and 2
      (VGLUT2) and the vesicular GABA transporter. Thus, in the LS, a separate
      population of neurons is covered by VGLUT3-ir PBs. The distribution pattern and
      the lack of co-localization indicate that the VGLUT3-expressing cells of origin
      are located in the brainstem and that they could be pure glutamatergic projection
      neurons-different from the well-defined canonical VGLUT1- and VGLUT2-expressing
      neurons. Alternatively, they could simultaneously express VGLUT3 and second
      transmitter, but use different release sites inside the LS for both.

PMID- 18611438
TI  - Regulation of calcineurin activity in insulin-secreting cells: stimulation by
      Hsp90 during glucocorticoid-induced apoptosis.
AB  - Previously, we described that apoptotic cell death induced by the synthetic
      glucocorticoid dexamethasone (dex) is inhibited by calcineurin inhibitors, FK506
      and deltamethrin, in insulin-secreting cells. The aim of the present study was to
      examine the mechanism of dex-dependent activation of calcineurin. In INS-1 cells
      cultured up to 4d with dex (100 nmol/l), the percentage of apoptosis, quantified
      by condensed nuclei and TUNEL positive cells, increased from 1% to 10.9%. FK506
      inhibited dex-mediated cell death. Apoptosis was significantly higher at glucose
      concentrations that induce [Ca(2+)](i) oscillations than at low, non-stimulatory
      glucose. Dex had no acute effect on [Ca(2+)](i). Calcineurin activity, measured
      in control and dex-treated cell homogenates, revealed that maximal activity and
      the sensitivity to the substrate RII peptide was unaltered. However, dex
      treatment significantly increased enzyme activity at submaximal, physiological
      Ca(2+) concentrations. Dex did not stimulate the Ca(2+)-dependent protease
      calpain, known to activate calcineurin by cleavage, as no cleaved calcineurin was
      detectable. Furthermore, the calpain inhibitor ALLN did not counteract dex
      dependent cell death. Western blotting revealed that in dex-treated cells heat
      shock protein 90 (Hsp90), a component of the glucocorticoid receptor (GR) known
      to stimulate calcineurin, was increased while calcineurin protein levels were
      unchanged. In immunoprecipitates with calcineurin antibodies, Hsp90 was only
      detected in dex-treated cell homogenates. These data suggest that dex-induced
      apoptosis involves release of Hsp90 from the stimulated GR complex, subsequent
      binding to and activation of calcineurin, that may contribute to dex-mediated
      cell death in the presence of high glucose.

PMID- 18611439
TI  - Antimicrobial peptides and self-DNA in autoimmune skin inflammation.
AB  - Toll-like receptor (TLR)-mediated detection of viral nucleic acids and production
      of type I interferons (IFNs) by plasmacytoid dendritic cells (pDCs) are key
      elements of antiviral defense. By contrast, inappropriate recognition of self
      nucleic acids with induction of IFN responses in pDCs can lead to autoimmunity.
      In this review we describe how pDC responses to self-DNA are normally avoided and
      focus on our recent finding that in psoriasis, a common autoimmune disease of the
      skin, these barriers can be breached by the cationic antimicrobial peptide LL37.
      LL37 binds extracellular self-DNA fragments into aggregated particles that enter
      pDCs and trigger robust IFN responses by activating endosomal TLR9 as if they
      were viruses. We also describe the mechanisms that normally control production
      and activity of LL37 in human skin and propose that the persistent overexpression
      of LL37 in psoriasis leads to uncontrolled IFN responses that drive autoimmune
      skin inflammation.

PMID- 18611440
TI  - Serine palmitoyltransferase inhibitor myriocin induces the regression of
      atherosclerotic plaques in hyperlipidemic ApoE-deficient mice.
AB  - Myriocin, a potent inhibitor of serine palmitoyltransferase (SPT), has been shown
      to reduce plasma sphingolipids, cholesterol and triglycerides in hyperlipidemic
      apolipoprotein E knockout (apoE KO) mice. We hypothesized that the inhibition of
      sphingolipid biosynthesis modulates the composition of atherosclerotic plaque via
      its lipid-lowering effects. To test this hypothesis, the effect of myriocin on
      plasma lipids, sphingolipids and atherosclerosis progression, regression and
      lesion composition was investigated in apoE KO mice. Myriocin was administered to
      24-week-old male apoE KO mice for 12 weeks. Myriocin-treated apoE KO mice had
      significant reductions in plasma total cholesterol, triglycerides, VLDL
      cholesterol, ceramide, sphinganine and sphingomyelin (SM) compared to 24- and 36
      week-old control mice. The ratio of SM to phosphatidylcholine (SM/PC), an
      independent risk factor for coronary artery disease, was also reduced by
      myriocin. Compared to 24- and 36-week controls, atherosclerotic lesion area and
      macrophage content in the aortic root and brachiocephalic arteries of myriocin
      treated ApoE KO mice were reduced but there was only a slight increase in smooth
      muscle content. However, the content of collagen within aortic root lesions was
      increased in myriocin-treated apoE KO mice. In summary, the inhibition of SPT
      lowers plasma sphingolipids and atherogenic plasma lipids leading to the
      regression of pre-existing atherosclerotic lesions and to the formation of a
      stable plaque phenotype.

PMID- 18611441
TI  - Imaging of the cell surface interface using objective coupled widefield surface
      plasmon microscopy.
AB  - We report on the development and on the first use of the widefield surface
      plasmon (WSPR) microscope in the examination of the cell surface interface at
      submicron lateral resolutions. The microscope is Kohler illuminated and uses
      either a 1.45 numerical aperture (NA) oil immersion lens, or a 1.65 NA oil
      immersion lens to excite surface plasmons at the interface between a thin gold
      layer and a glass or sapphire cover slip. Like all surface plasmon microscope
      systems the WSPR has been proven in previous studies to also be capable of
      nanometric z-scale resolutions. In this study we used the system to image the
      interface between HaCaT cells and the gold layer. Imaging was performed in air
      using fixed samples and the 1.45 NA objective based system and also using live
      cells in culture media using the 1.65 NA based system. Imaging in air enabled the
      visualisation of high resolution and high-contrast submicron features identified
      by vinculin immunostaining as component of focal contacts and focal adhesions. In
      comparison, imaging in fluid enabled cell surface interfacial interactions to be
      tracked by time-lapse video WSPR microscopy. Our results indicate that the cell
      surface interface and thus cell signalling mechanisms may be readily interrogated
      in live cells without the use of labelling techniques.

PMID- 18611442
TI  - In situ genetic differentiation in a Hispaniolan lizard (Ameiva chrysolaema): a
      multilocus perspective.
AB  - A previous phylogeographic study of mitochondrial haplotypes for the Hispaniolan
      lizard Ameiva chrysolaema revealed deep genetic structure associated with
      seawater inundation during the late Pliocene/early Pleistocene and evidence of
      subsequent population expansion into formerly inundated areas. We revisit
      hypotheses generated by our previous study using increased geographic sampling of
      populations and analysis of three nuclear markers (alpha-enolase intron 8, alpha
      cardiac-actin intron 4, and beta-actin intron 3) in addition to mitochondrial
      haplotypes (ND2). Large genetic discontinuities correspond spatially and
      temporally with historical barriers to gene flow (sea inundations). NCPA cross
      validation analysis and Bayesian multilocus analyses of divergence times (IMa and
      MCMCcoal) reveal two separate episodes of fragmentation associated with Pliocene
      and Pleistocene sea inundations, separating the species into historically
      separate Northern, East-Central, West-Central, and Southern population lineages.
      Multilocus Bayesian analysis using IMa indicates asymmetrical migration from the
      East-Central to the West-Central populations following secondary contact,
      consistent with expectations from the more pervasive sea inundation in the
      western region. The West-Central lineage has a genetic signature of population
      growth consistent with the expectation of geographic expansion into formerly
      inundated areas. Within each lineage, significant spatial genetic structure
      indicates isolation by distance at comparable temporal scales. This study adds to
      the growing body of evidence that vicariant speciation may be the prevailing
      source of lineage accumulation on oceanic islands. Thus, prior theories of island
      biogeography generally underestimate the role and temporal scale of intra-island
      vicariant processes.

PMID- 18611443
TI  - Selection of objective function in genome scale flux balance analysis for process
      feed development in antibiotic production.
AB  - Using flux variability analysis of a genome scale metabolic network of
      Streptomyces coelicolor, a series of reactions were identified, from disparate
      pathways that could be combined into an actinorhodin-generating mini-network.
      Candidate process feed nutrients that might be expected to influence this network
      were used in process simulations and in silico predictions compared to
      experimental findings. Ranking potential process feeds by flux balance analysis
      optimisation, using either growth or antibiotic production as objective function,
      did not correlate with experimental actinorhodin yields in fed processes.
      However, the effect of the feeds on glucose assimilation rate (using glucose
      uptake as objective function) ranked them in the same order as in vivo antibiotic
      production efficiency, consistent with results of a robustness analysis of the
      effect of glucose assimilation on actinorhodin production.

PMID- 18611444
TI  - Ribosome inactivating protein saporin induces apoptosis through mitochondrial
      cascade, independent of translation inhibition.
AB  - Ribosome inactivating proteins (RIPs) are toxic translation inhibitors that kill
      eukaryotic cells by arresting protein synthesis at the translocation step.
      Saporin-6, expressed in the seeds of Saponaria officinalis plant, is a type I RIP
      comprising of a single polypeptide chain. Saporin is a specific RNA N-glycosidase
      and it removes a specific adenine residue from a conserved loop of the large rRNA
      of eukaryotic cells. Saporin-6 is one of the most potent of several isoforms of
      saporin, obtained from different tissues of the Saponaria plant. In addition to
      potently inhibiting translation, saporin has been also shown to induce cell death
      by apoptosis in different cellular models. To elucidate the mechanism of
      apoptosis induction by saporin, we have investigated the apoptotic pathway
      triggered by saporin. We have also analyzed whether the inhibition of protein
      synthesis by the toxin is the trigger for induction of apoptosis. We demonstrate
      that saporin-6 induces caspase-dependent apoptosis in U937 cells via the
      mitochondrial or intrinsic pathway. Unlike many other toxins the catalytic N
      glycosidase activity of saporin is not required for apoptosis induction, and the
      apoptosis onset occurs before any significant inhibition of protein synthesis
      ensues.

PMID- 18611445
TI  - Decreased ER-associated degradation of alpha-TCR induced by Grp78 depletion with
      the SubAB cytotoxin.
AB  - HeLa cells stably expressing the alpha chain of T-cell receptor (alphaTCR), a
      model substrate of ER-associated degradation (ERAD), were used to analyze the
      effects of BiP/Grp78 depletion by the SubAB cytotoxin. SubAB induced XBP1
      splicing, followed by JNK phosphorylation, eIF2alpha phosphorylation,
      upregulation of ATF3/4 and partial ATF6 cleavage. Other markers of ER stress,
      including elements of ERAD pathway, as well as markers of cytoplasmic stress,
      were not induced. SubAB treatment decreased absolute levels of alphaTCR, which
      was caused by inhibition of protein synthesis. At the same time, the half-life of
      alphaTCR was extended almost fourfold from 70 min to 210 min, suggesting that BiP
      normally facilitates ERAD. Depletion of p97/VCP partially rescued SubAB-induced
      depletion of alphaTCR, confirming the role of VCP in ERAD of alphaTCR. It
      therefore appears that ERAD of alphaTCR is driven by at least two different ATP
      ase systems located at two sides of the ER membrane, BiP located on the lumenal
      side, while p97/VCP on the cytoplasmic side. While SubAB altered cell morphology
      by inducing cytoplasm vacuolization and accumulation of lipid droplets, caspase
      activation was partial and subsided after prolonged incubation. Expression of
      CHOP/GADD153 occurred only after prolonged incubation and was not associated with
      apoptosis.

PMID- 18611447
TI  - Diurnal lamotrigine plasma level fluctuations: clinical significance and
      indication of shorter half-life with chronic administration.
AB  - For therapeutic monitoring of antiepileptic drugs (AEDs), morning trough levels
      (MTLs) are generally used. For specific questions like verification of
      breakthrough seizures or reported toxicity, however, other measures such as
      minimal and maximal concentrations (C(min), C(max)) can be important and may
      require daily profiles. For clinical reasons, 20 daily profiles of lamotrigine
      (LTG) plasma levels were determined in nine patients. The results revealed
      fluctuations exceeding those expected from its elimination half-life (t(1/2)) of
      22h as reported in the literature. Patients on twice-daily regimens without
      pharmacokinetic interactions exhibited C(min)/C(max) ratios between 0.62 and
      0.69. Fluctuations were smaller in those co-medicated with valproate, and reached
      a ratio of 0.55 in those co-medicated with phenobarbital. The C(max) was as much
      as 58% above the MTL. Therefore, verification of complaints indicating toxicity
      requires determination of drug levels when the symptoms are present. Our findings
      indicate that the t(1/2) of LTG with chronic treatment is shorter than generally
      assumed, and suggest that a slow-release formulation could be helpful in
      achieving full seizure control in patients with a narrow individual therapeutic
      index for LTG.

PMID- 18611446
TI  - Compensatory brain activation for recognition memory in patients with medication
      resistant epilepsy.
AB  - Progressive decline of memory functions has been observed in patients with
      chronic medication-resistant epilepsy. The progression likely relates to the
      effects of epileptiform discharges, seizures, and medications on the processes of
      encoding and retrieval. The goal of the study described here was to use
      functional MRI (fMRI) to examine the effects of chronic epilepsy on verbal
      recognition memory. We enrolled 12 patients with medication-resistant epilepsy (5
      with right and 7 with left hemispheric seizure onset) and 18 healthy controls
      matched for age, gender, and handedness. Subjects underwent fMRI at 3T using a
      word recognition task during which they had to recall if words presented during
      scanning were words they had learned prior to scanning. Although we noted many
      similarities in the fMRI activation patterns between the subjects with epilepsy
      and the healthy subjects in areas typically involved in memory processing,
      testing of the interaction effects for target-foil differences between groups
      revealed several differences in activation including the right insula, the left
      cuneus, and the bilateral subgenual anterior cingulate cortex (ACC). In patients
      with epilepsy, these regions exhibited greater activation for targets than foils,
      but in healthy subjects the difference was reversed (right insula), absent (left
      cuneus), or included deactivation to target words (pregenual ACC). These
      differences were seen despite similar performance during the memory task,
      suggesting that activations observed in these additional regions may represent
      compensatory processes for verbal recognition memory that are induced by chronic
      brain injury related to recurrent seizures.

PMID- 18611448
TI  - Isolation and characterization of a hyaluronidase from the venom of Chinese red
      scorpion Buthus martensi.
AB  - A hyaluronidase, named BmHYA1, was purified from the venom of Chinese red
      scorpion (Buthus martensi), using successive chromatography. The homogeneity of
      BmHYA1 was confirmed by SDS-PAGE and MALDI-TOF mass spectrometry. The molecular
      mass of BmHYA1 was 48,696 Da determined by MALDI-TOF MS. The optimal temperature
      and pH of BmHYA1 were 50 degrees C and pH 4.5, respectively. It could be
      inhibited by DTT, Cu(2+), Fe(3+) or heparin, but not Mg(2+), Ca(2+), reduced
      glutathione, l-cysteine or EDTA. The sequence of thirty N-terminal amino acids of
      BmHYA1 was obtained by Edman degradation, as TSADF KVVWE VPSIM CSKKF KICVT DLLTS;
      but no similarity was found to other venom hyaluronidases. Further, BmHYA1 can
      hydrolyze hyaluronan into relatively smaller oligosaccharides and modulate the
      expression of CD44 variant in the breast cancer cell line MDA-MB-231.

PMID- 18611449
TI  - Pro-inflammatory genetic background and zinc status in old atherosclerotic
      subjects.
AB  - Inflammation and genetics are prominent mechanisms in the pathogenesis of
      atherosclerosis (AT) and its complications. In this review we discuss the
      possible impact on AT development of several genetic determinants involved in
      inflammation, oxidative stress and cytoprotection (IL-6, TNF-alpha, IL-10, CD14,
      TLR4, MT, HSP70). Genetic polymorphisms of these genes may affect a differential
      inflammatory response predisposing to AT. However, allelic polymorphisms of genes
      which increase the risk of AT frequently occur in the general population but,
      only adequate gene-environment-polymorphism interactions promote the onset of the
      disease. Zinc deficiency has been suggested as an environmental risk factor for
      AT. With advancing age, the incidence of zinc deficiency increases for several
      reasons. Among them, dietary intake, malabsorption and genetic background of
      inflammatory markers may be involved. A crucial contribution may also be played
      by increased oxidative stress which may lead to the appearance of dysfunctional
      proteins, including metallothioneins (MT) that are in turn involved in zinc
      homeostasis. The detection of candidate genes related to inflammation and
      promoting AT and their reciprocal influence/interaction with zinc status might
      allow earlier appropriate dietary interventions in genetically susceptible
      subjects.

PMID- 18611450
TI  - Acute Influenza A infection induces bronchial hyper-responsiveness in mice.
AB  - This study aimed to determine whether the route of administration of methacholine
      (MCh) influenced the pattern of airway hyper-responsiveness (AHR) in mice. BALB/c
      mice were inoculated with a 50-microL volume containing 10(4.5)-pfu Influenza
      virus A/Mem/1/71(H3N1) or media. MCh responsiveness in vivo [inhaled (0.01-30
      mg/mL), i.v. MCh (6-48 microg/min/kg)] and in vitro were measured at day 4 post
      infection (D4) during acute lower respiratory infection (LRI) and following
      resolution of infection at day 20 (D20) using a low-frequency, forced oscillation
      technique. Inflammation was assessed in bronchoalveolar lavage fluid. Infected
      mice had pulmonary inflammation and heightened responsiveness to both inhaled
      (p<0.03) and intravenous (p<0.02) MCh on D4, but not on D20. In vitro
      responsiveness was not altered at either time point. Influenza A LRI results in
      AHR during acute infection associated with a marked inflammatory response and
      increased permeability of the alveolar-capillary barrier. These data suggest that
      intrinsic muscle properties are not altered but MCh has greater access to airway
      smooth muscle during acute infection.

PMID- 18611452
TI  - Development of a method for analysis of Iranian damask rose oil: combination of
      gas chromatography-mass spectrometry with Chemometric techniques.
AB  - Gas chromatography-mass spectrometry (GC-MS) combined with Chemometric resolution
      techniques were proposed as a method for the analysis of volatile components of
      Iranian damask rose oil. The essential oil of damask rose was extracted using
      hydrodistillation method and analyzed with GC-MS in optimized conditions. A total
      of 70 components were identified using similarity searches between mass spectra
      and MS database. This number was extended to 95 components with concentrations
      higher than 0.01% accounting for 94.75% of the total relative content using
      Chemometric techniques. For the first time in this work, an approach based upon
      subspace comparison is used for determination of the chemical rank of GC-MS data.
      The peak clusters were resolved using heuristic evolving latent projection (HELP)
      and multivariate curve resolution-alternating least square (MCR-ALS) by applying
      proper constraints, and the combination of both methods for some cases. It is
      concluded that a thorough analysis of the complex mixtures such as Iranian damask
      rose requires sophisticated GC-MS coupled with the Chemometric techniques.

PMID- 18611451
TI  - Review of molecular modification techniques for improved detection of
      biomolecules by mass spectrometry.
AB  - After a soft ionizing method was established, MS (mass spectrometry) has become a
      more common tool in biochemistry because soft ionization made it possible to
      detect large molecules such as proteins. Many kinds of applications were
      established to further utilize MS for the identification or quantitation of
      biomolecules. In this review, we introduce recent applications with special focus
      on chemical modification techniques and chemical probes developed for the MS
      determination of biomolecules.

PMID- 18611453
TI  - Calibration model transfer for near-infrared spectra based on canonical
      correlation analysis.
AB  - In order to solve the calibration transformation problem in near-infrared (NIR)
      spectroscopy, a method based on canonical correlation analysis (CCA) for
      calibration model transfer is developed in this work. Two real NIR data sets were
      tested. A comparative study between the proposed method and piecewise direct
      standardization (PDS) was conducted. It is shown that the transfer results
      obtained with the proposed method based on CCA were better than those obtained by
      PDS when the subset had sufficient samples.

PMID- 18611454
TI  - Model based substrate set point control of yeast cultivation processes based on
      FIA measurements.
AB  - In this contribution a model based substrate control system for Saccharomyces
      cerevisiae fed batch cultivations is presented. The intention is to keep the
      concentration of the substrate glucose at a fixed selected set point during the
      process run. Set points of 0.07 g L(-1) and 0.5 g L(-1) are chosen, as the cells
      change their metabolism from pure oxidative to oxidative-reductive depending on
      the glucose concentration. The precise control of glucose concentration during
      cultivations still poses a challenge as the analysis with available on-line
      measurement systems still has the problem of noise and a time delay of at least 6
      min. To compensate these effects a control system based on an ordinary FIA system
      for glucose measurements complemented by an extended Kalman filter is employed.
      The Kalman filter could handle the dynamics of the process accurately. Based on
      the glucose measurement every 3 min it estimated the biomass and glucose
      concentration as well as the growth rate factor and the volume of the culture
      broth. Utilising the estimated values of the process variables a feed forward
      controller was complemented by a PI controller to adjust the glucose
      concentration at the desired set points. During the control phase the standard
      deviation of the measurements are 0.002 g L(-1) and 0.022 g L(-1) for the set
      points of 0.07 g L(-1) and 0.5 g L(-1), respectively.

PMID- 18611455
TI  - Bilinear least squares (BLLS) and molecular fluorescence in the quantification of
      the propranolol enantiomers.
AB  - The quantification of mixtures of (R)- and (S)-propranolol (PRO) in the pure form
      and in the pharmaceutical preparations is described. The methodology is based on
      chiral recognition of propranolol by formation of an inclusion complex with beta
      cyclodextrin (CD), a chiral auxiliary, in the presence of 1-butanol. The
      excitation-emission fluorescence surface and second-order multivariate
      calibration such as bilinear least squares (BLLS) and parallel factor analysis
      (PARAFAC) were used in the model development. BLLS performed better than PARAFAC,
      presenting relative mean error in the order of 3.5%, analytical sensitivity of
      0.07% and 0.08%, detection limit of 0.23% and 0.28% and quantification limit of
      0.71% and 0.84% for the pure form and pharmaceutical preparations, respectively.
      These results indicate that the proposed methodology can be an alternative for
      the determination of propranolol enantiomeric composition.

PMID- 18611456
TI  - Selective extraction, separation and speciation of iron in different samples
      using 4-acetyl-5-methyl-1-phenyl-1H-pyrazole-3-carboxylic acid.
AB  - A method for speciation, preconcentration and separation of Fe(II) and Fe(III) in
      different matrices was developed using solvent extraction and flame atomic
      absorption spectrometry. 4-Acetyl-5-methyl-1-phenyl-1H-pyrazole-3-carboxylic acid
      (AMPC) was used as a new complexing reagent for Fe(III). The Fe(III)-AMPC complex
      was extracted into methyl isobutyl ketone (MIBK) phase in the pH range 1.0-2.5,
      and Fe(II) ion remained in aqueous phase at all pH. The chemical composition of
      the Fe(III)-AMPC complex was determined by the Job's method. The optimum
      conditions for quantitative recovery of Fe(III) were determined as pH 1.5,
      shaking time of 2 min, 1.64x10(-4) mol L(-1) AMPC reagent and 10 mL of MIBK.
      Furthermore, the influences of diverse metal ions were investigated. The level of
      Fe(II) was calculated by difference of total iron and Fe(III) concentrations. The
      detection limit based on the 3sigma criterion was found to be 0.24 microg L(-1)
      for Fe(III). The recoveries were higher than 95% and relative standard deviation
      was less than 2.1% (N=8). The validation of the procedure was performed by the
      analysis of two certified standard reference materials. The presented method was
      applied to the determination of Fe(II) and Fe(III) in tap water, lake water,
      river water, sea water, fruit juice, cola, and molasses samples with satisfactory
      results.

PMID- 18611457
TI  - Chemical switch based reusable dual optoelectronic sensor for nitrite.
AB  - An optical sensor was developed for sensing of nitrite based on the monotonous
      decrease in absorbance of Rhodamine 6G at 525 nm (the absorbance maximum of dye)
      with increasing concentration of nitrite. This sensor also permits naked eye
      detection. Various parameters like concentrations of sulphuric acid and Rhodamine
      6G, response time and stability were varied and optimal conditions are reported.
      Under these conditions, the developed sensor enables the determination of nitrite
      in the concentration range 0-12.18 micromol L(-1). The nitrite response is
      selective as 60-2.5x10(5) fold amounts of several anions and cations have no
      deleterious effect. The addition of nitrite to Rhodamine 6G dye causes
      hypsochromic shift from 525 to 385 nm while several other anions like I(-), SCN(
      ), ClO(4)(-), [HgI(4)](2-) and [Zn (SCN)(4)](2-) showed a bathochromatic shift
      from 525 to 575 nm. The sequential addition of nitrite and sulphamic to Rhodamine
      6G in 0.75 mol L(-1) sulphuric acid solution results in switching of "ON" and
      "OFF" absorbance. The time elapse and concentration of sulphamic acid required
      for chemical switching was also established. Similar "ON" and "OFF" switching
      behaviour was observed in fluorescence studies also. This enabled the design and
      development of reusable chemical switch based dual optoelectronic sensor, for
      monitoring of traces of nitrite in environmental and food samples. The plausible
      mechanism for above switching behaviour is also proposed.

PMID- 18611458
TI  - Determination of gas phase triacetone triperoxide with aspiration ion mobility
      spectrometry and gas chromatography-mass spectrometry.
AB  - Aspiration ion mobility spectrometry (IMS) has been used for the first time to
      screen 3,3,6,6,9,9-hexamethyl-1,2,4,5,7,8-hexaoxacyclononane explosive, the most
      commonly known as triacetone triperoxide (TATP). Gaseous TATP was generated from
      synthesized solid compound, sublimed and directed to a portable chemical
      detection system comprised of an aspiration-type IMS detector and six
      semiconductor sensors. Different unknown TATP gas phase concentrations were
      produced and corresponding IMS and semiconductor responses were measured. The
      experimental concentrations were determined by gas chromatography-mass
      spectrometry (GC-MS). The results evidenced that the monitored compound in the
      gas phase was TATP. In addition, the determined TATP concentrations and
      corresponding IMS intensities showed that the IMS response values were
      proportional to the measured TATP concentrations.

PMID- 18611460
TI  - Development of disposable bulk-modified screen-printed electrode based on bismuth
      oxide for stripping chronopotentiometric analysis of lead (II) and cadmium (II)
      in soil and water samples.
AB  - A bulk-modified screen-printed carbon electrode characterised for metal ion
      detection is presented. Bismuth oxide (Bi(2)O(3)) was mixed with graphite-carbon
      ink to obtain the modified electrode. The best composition was 2% Bi(2)O(3) (wt%)
      in the graphite-carbon ink. The modified electrode with onboard screen-printed
      carbon counter and silver-silver chloride pseudo-reference electrodes exhibited
      good performance in the electrochemical measurement of lead (II) and cadmium
      (II). The electrode displayed excellent linear behaviour in the concentration
      range examined (20-300 microg L(-1)) with limits of detection of 8 and 16 microg
      L(-1) for both lead (II) and cadmium (II), respectively. The analytical utility
      of the modified electrode was illustrated by the stripping chronopotentiometric
      determinations of lead (II) in soil extracts and wastewater samples.

PMID- 18611461
TI  - Synthesis of nano-pore samarium (III)-imprinted polymer for preconcentrative
      separation of samarium ions from other lanthanide ions via solid phase
      extraction.
AB  - A batch process was developed to separate samarium ions from some lanthanide ions
      by a novel solid phase which was prepared via the ion-imprinting technique. The
      samarium (III) ion-imprinted polymer (IIP) particles were synthesized by
      preparing the ternary complex of samarium ions with 5,7-dichloroquinoline-8-ol
      (DCQ) and 4-vinylpyridine (VP). Then, thermally copolymerization with styrene
      (functional monomer, STY) and divinylbenzene (cross-linking monomer, DVB)
      followed in the presence of 2-methoxy ethanol (porogen) and 2,2'
      azobisisobutyronitrile (initiator, AIBN). The imprinted ion was removed by
      stirring the above particles with 50% (v/v) HCl to obtain the leached IIP
      particles. Moreover, control polymer (CP) particles were similarly prepared
      without the samarium ions. The unleached and leached IIP particles were
      characterized by X-ray diffraction (XRD), infra-red spectroscopy (IR), thermo
      gravimetric analysis (TGA) and scanning electron microscopy (SEM). Finally,
      preconcentration and selectivity studies for samarium and the other lanthanide
      ions were carried out. The preconcentration of the samarium (III) traces was
      studied during rebinding with the leached IIP particles as a function of pH, the
      weight of the polymer material, the preconcentration and the elution times, the
      eluent volume and the aqueous phase volume. These studies indicated that the
      samarium (III) amount as low as 1 microg, present in 200 mL, could be
      preconcentrated into 25 mL of 1.0 M HCl.

PMID- 18611459
TI  - Monitoring of influenza virus hemagglutinin in process samples using weak
      affinity ligands and surface plasmon resonance.
AB  - Surface plasmon resonance (SPR) was used to screen the interaction between a
      variety of affinity ligands and hemagglutinin (HA) from human influenza virus,
      with the aim of identifying low affinity ligands useful for the development of a
      rapid bioanalytical sensor. Three sialic acid-based structures and four lectins
      were evaluated as sensor ligands. The sialic acid-based ligands included a
      natural sialic acid-containing glycoprotein, human alpha1-acid glycoprotein
      (alpha1-AGP), and two synthetic 6'-sialyllactose-conjugates, with varying degree
      of substitution. The interaction of HA with the four lectin-based ligands,
      concanavalin A (Con A), wheat germ agglutinin (WGA), Maackia amurensis lectin
      (MAL), and Sambucus nigra agglutinin (SNA), showed a wide variation of affinity
      strengths. Affinity and kinetics data were estimated. Strong affinities were
      observed for Con A, WGA, alpha1-AGP, and a 6'-sialyllactose-conjugate with a high
      substitution degree, and low affinities were observed for MAL and a 6'
      sialyllactose-conjugate with low substitution. The main objective, to identify a
      low affinity ligand which could be used for on-line monitoring and product
      quantification, was met by a 6'-sialyllactose-ovalbumin conjugate that had 0.6
      mol ligand per mol carrier protein. The apparent affinity of this ligand was
      estimated to be 1.5+/-0.03 microM (K(D)) on the SPR surface. Vaccine process
      samples containing HA were analyzed in the range 10-100 microg HA mL(-1) and
      correlated with single-radial immunodiffusion. The coefficient of variation on
      the same chip was between 0.010 and 0.091.

PMID- 18611462
TI  - Simultaneous determination of amiodarone and its metabolite desethylamiodarone by
      high-performance liquid chromatography with chemiluminescent detection.
AB  - A novel method was developed for the determination of amiodarone and
      desethylamiodarone by high-performance liquid chromatography (HPLC) coupled with
      chemiluminescent (CL) detection. The procedure is based on the post-column
      photolysis of the analytes into photoproducts which are active in the tris(2,2'
      bipyridyl)ruthenium(III) [Ru(bpy)(3)(3+)] CL system. Ru(bpy)(3)(3+) was on-line
      generated by photo-oxidation of the Ru(II) complex in the presence of
      peroxydisulfate. The separation was carried out on a Mediterranea C(18) column
      with isocratic elution using a mixture of methanol and 0.017 mol L(-1) ammonium
      sulfate buffer of pH 6.8. Under the optimum conditions, analytical curves, based
      on standard solutions, were linear over the range 0.1-50 microg mL(-1) for
      amiodarone and 0.5-25 microg mL(-1) for desethylamiodarone. The detection limits
      of amiodarone and desethylamiodarone were 0.02 and 0.11 microg mL(-1),
      respectively. Intra- and inter-day precision values of 0.9% relative standard
      deviation (R.S.D.) (n=10) and 1.6% R.S.D. (n=15), respectively, were obtained.
      The method was applied successfully to the determination of these compounds in
      serum and pharmaceutical formulations.

PMID- 18611463
TI  - Direct electrogenerated chemiluminescence detection in high-performance liquid
      chromatography for determination of ofloxacin.
AB  - Ofloxacin (OFLX) exhibited strong electrogenerated chemiluminescence (ECL) in
      NaNO(3) solution with a dual-electrode system when constant current was exerted.
      Based on this observation, a sensitive direct ECL method coupled with high
      performance liquid chromatography (HPLC) separation was developed for
      determination of OFLX in human serum. Factors affected the ECL emission were
      investigated. Under the optimal conditions, the ECL intensity has a linear
      relationship with the concentration of OFLX in the range of 1.0x10(-8) to 4.0x10(
      6) g mL(-1) and the detection limit was 4x10(-9) g mL(-1) (S/N=3). The proposed
      method was sensitive, simple and convenient to operate.

PMID- 18611464
TI  - Development of a molecularly imprinted polymer for pyridoxine using an ion-pair
      as template.
AB  - One of the main challenges in the molecularly imprinted polymers (MIP) field is
      the proper MIP design for water-soluble compounds because of appearance of
      serious drawbacks in polar solvents and insolubility of those compounds in non
      polar solvents which are commonly used for MIP synthesis. In this work a novel
      and simple method for synthesis of molecularly imprinted polymers for a water
      soluble compound was introduced. Pyridoxine was chosen as a target molecule and
      the ion-pair complex formed between pyridoxine ion (Py(+)) and dodecyl sulfate
      ion (DS(-)) was transferred into the chloroform via liquid-liquid extraction.
      Then polymerization was carried out in chloroform. The molecular mechanics and
      density functional theory were proposed to screen proper monomer. Binding energy,
      DeltaE, of a template and a monomer as a measure of their interaction was
      considered. Ion-pair [Py(+)-DS(-)] was supposed as a template molecule and
      acrylic acid, methacrylic acid, allyamine, vinylpridine and 2-hydroxy ethyl
      methacrylate were as tested monomers. The MIP synthesized using acrylic acid
      showed the highest selectivity to pyridoxine as predicted from the DeltaE
      calculation. The obtained MIP showed very high affinity against vitamin B6 in
      comparison to non-imprinted polymers (NIP). It was proved that the obtained MIP
      with introduced method was much better than that prepared in methanol as porogen.
      It was showed that the MIP prepared by this new method could be used as an
      adsorber for extraction and determination of pyridoxine in real and synthetic
      samples.

PMID- 18611465
TI  - On-site determination of formaldehyde: a low cost measurement device for museum
      environments.
AB  - A trapping reagent for formaldehyde, based on the pararosaniline reaction, was
      evaluated as a method of determination of formaldehyde in the aqueous or vapour
      phase. Collection of formaldehyde vapour relied upon passive diffusion of
      formaldehyde into the trapping media and quantitative results were obtained
      without the need for liquid impingers, bubblers or active sampling pumps.
      Moreover, a novel, hand-held absorption spectrophotometric measurement device was
      designed to provide on-site, quantitative measurements. It is proposed that the
      full measurement system devised would be ideally suited to specific sampling
      applications such as those found in museum enclosures.

PMID- 18611466
TI  - Effect of chloroquine on lysosomes and on growth of mouse hepatitis virus (MHV
      3).
AB  - After a 6-hour treatment with chloroquine, infected mouse peritoneal macrophages
      produce markedly less mouse hepatitis virus than untreated cells. Macrophages
      maintained in culture for 72 hours after the treatment produce a higher virus
      yield. Cytochemical investigations immediately and 3 days after chloroquine
      treatment show an increased permeability of the lysosomes of the latter.
      Variations of the enzymes escaping from the lysosomes are thought to be
      responsible for differences in virus uncoating and consequent virus yield.

PMID- 18611467
TI  - Host controlled modification of the transducing activities of lambda phage.
AB  - Transducing lambdadg produced by growth in Escherichia coli C is restricted in
      its ability to transduce the galactose genes into E. coli K. Plaque-forming
      lambda grown in C is similarly restricted in providing the helper function for
      transduction. However, at higher multiplicities of infection restricted lambda
      shows cooperative effects in providing helper function (analogous to those seen
      in the initiation of a lytic cycle), and the helper function may equal or exceed
      that provided by unrestricted phage. The capacity of restricted lambda to provide
      helper function is greatly reduced if the infected complexes are formed during a
      brief period of anaerobiosis. This parallels the anaerobic effect on cooperative
      infection reported in earlier studies. These observations are consistent with the
      two-step model for the restriction of the vegetative growth of host-modified
      lambda.

PMID- 18611468
TI  - Analysis of defectiveness of Rous sarcoma virus. IV. Kinetics of RSV production.
AB  - The growth kinetics of a defective strain of RSV was studied under two different
      conditions. In the first, helper viruses having different growth rates were added
      to non-virus-producing Rous cells in which infection by RSV without helper virus
      had been established. In the second, RSV was added to chick embryo cells which
      had previously been infected with helper virus and which were, therefore, in full
      production of viral coats. In the first instance, the initial rate of RSV
      production was regulated by the growth rate of the helper virus added; in the
      second, the initial rate of RSV production was independent of that of the helper
      virus used for preinfection of cells. The results strongly support the idea that
      the rate of RSV production depends on the supply of viral coat from the helper
      virus.

PMID- 18611469
TI  - An estimation of the overlap bias in plaque assay.
AB  - A systematic underestimation of the density of PFU's of a virus suspension is
      caused by overlapping plaques. The degree of this bias depends on n, the number
      of plaques distributed over the petri dish and on d, the (mean) diameter of the
      plaques. The mean number of overlapping events, y, is proportional to n2 and to
      d2, y = cn2d2. If the experimental circumstances yield values of n or d or of
      both, which are too large, incorrect inferences may be drawn from the outcome of
      a quantitative plaque test. For example, there is danger that an existing
      difference in the concentration of two virus-suspensions will not be detected. It
      is of interest, therefore, to evaluate c, the factor of proportionality. From
      this an equation may be derived which relates the number of observed plaques
      (including the unknown number of overlapping events) directly to the expected
      true number of plaques on the dish. Furthermore, upper limits of the number of
      observed plaques, which should not be exceeded in experimentation to avoid any
      overlap are given at several levels of d for 5-cm dishes. The evaluation of c was
      performed by a set of Monte Carlo procedures.

PMID- 18611470
TI  - Studies on phage development. II. The maturation of T4 phage in the presence of
      puromycin.
AB  - Maturation of T4 can proceed in the presence of 5-methyltryptophan or puromycin.
      Puromycin inhibits phage protein synthesis within a few seconds, thus limiting
      the amount of phage precursor material available for maturation. After the arrest
      of protein synthesis, maturation continues unabated until the limiting protein
      precursor is depleted. At least one protein, the tail fiber protein, is depleted.
      Phage protein maturable in the presence of puromycin appears about 5 minutes
      before maturation begins. The level of the maturable material reaches a maximum
      at the beginning of maturation. This level is taken as a measure of the size of
      the pool of complete sets of maturable phage protein. The bulk precursor protein
      begins to accumulate 3 minutes earlier than serum blocking proteins (SBP) and
      forms a pool about twice as large as the pool of SBP.

PMID- 18611471
TI  - Studies on phage development. III. The fate of T4 DNA and protein synthesized in
      the presence of 9-aminoacridine.
AB  - 9-Aminoacridine (9AA) inhibits maturation of phage T4. Upon diluting infected
      bacteria from the dye into a medium containing an inhibitor of protein synthesis,
      one obtains a crop of mature phage made out of the material accumulated before
      the removal of 9AA. DNA is synthesized in the presence of 9AA and continues to
      replicate after the removal of 9AA and addition of puromycin. By marking the DNA
      with 5-bromodeoxyuridine (BUDR) and studying the light sensitivity of the phage
      produced by cells exposed to 9AA, BUDR and puromycin in various programs, one can
      show that the DNA made in the presence of 9AA is incorporated later into viable
      phage. This early DNA is dispersed through the DNA synthesized after the removal
      of the dye. The DNA can in the presence of puromycin pass from the vegetative
      into the condensed state and subsequently be coated with the protein material
      synthesized in the presence of the dye.

PMID- 18611472
TI  - An electron microscopic study of changes at the surface of influenza-infected
      cells as revealed by ferritin-conjugated antibodies.
AB  - The sequence of events associated with liberation of the PR8 strain of influenza
      virus at the surface of chorioallantoic membranes (CAM) was studied by means of
      ferritin-conjugated antibodies, one of which was specific for the V antigen of
      the virus and the other for host cell antigen. With an input multiplicity of
      approximately 0.001 per cell, viral progeny were first detected by infectivity
      titrations and electron-microscopy after 12 and 13 hours, respectively. As
      infection proceeded, viral antigen progressively accumulated at the cell surface,
      while host cell antigen diminished in amount. It was concluded that normal host
      cell protein did not constitute an integral part of the surface structure of the
      virus.

PMID- 18611473
TI  - Mapping of prophage P22 in Salmonella typhimurium.
AB  - Mutants resistant to phage P22 by virtue of roughness, due to mutation at rouB,
      were obtained in P22-lysogenic and nonlysogenic forms of two genetically marked
      lines of Salmonella typhimurium strain LT2. Crosses permuted in respect of the
      lysogeny or nonlysogeny of the rough metA tryB donor and of the rough adeC proA
      ile str-r acceptor line were then made, using the colicine factors colI and colE1
      to obtain conjugation and recombination. When the donor was P22-lysogenic and the
      acceptor was nonlysogenic there was a great reduction in the yield of
      recombinants with the linked azi, pro, and gal alleles of the donor. In the cross
      of the nonlysogenic donor to the lysogenic acceptor the yield of recombinants
      with the pro+ donor allele was normal. In this cross all the recombinant clones
      with the pro+ allele from the donor were either nonlysogenic or mixed in respect
      of lysogeny, though homogeneous in respect of all other segregating characters.
      By contrast only one of 54 recombinants with the ile+, but not the pro+, donor
      allele was nonlysogenic. The results suggest that in lysogenic S. typhimurium
      strain LT2 prophage P22 is always or nearly always located on or in the
      chromosome very close to proA.

PMID- 18611474
TI  - Electron microscope observations of African swine fever virus in tissue culture
      cells.
AB  - African swine fever virus, Hinde isolate, grown in a stable pig kidney cell line
      and primary pig kidney cells, was examined for successive stages in the
      development of the virus particle. The mature particle has a hexagonal outer
      membrane structure (diameter 175-215 micron) surrounding an electron lucent
      region and a dense nucleoid (diameter 72-89 micron). The increase in particle
      production in the cell cytoplasm is consistent with both the rise in infectivity
      as measured in pig kidney cell cultures and the rise of hemadsorption titer as
      measured in leukocyte cultures.

PMID- 18611475
TI  - Susceptibility of cells in different stages of the mitotic cycle to
      transformation by polyoma virus.
AB  - The susceptibility to malignant transformation by polyoma virus of cells infected
      in different phases of the mitotic cycle has been studied using the hamster
      fibroblast line BHK21 (clone 13). It appears that cell competence is not
      restricted to a portion of the mitotic cycle. However, susceptibility to
      transformation increases with the progress of the cell through interphase. The
      variations observed cannot be entirely ascribed to different degrees of virus
      adsorption. Moreover, the possibility that the cells engaged in DNA synthesis are
      the most susceptible has been excluded. The results are consistent with the
      hypothesis that the probability of transformation of a cell is directly related
      to its DNA content at the time of infection.

PMID- 18611476
TI  - Mutants of the bacteriophage f2. VI. Homology of temperature-sensitive and host
      dependent mutants.
AB  - Temperature-sensitive mutants of phage f2 have been isolated and classified into
      three groups by physiological criteria. One group is blocked at an early stage of
      growth and synthesizes neither phage RNA nor phage antigen at high temperature. A
      second group of mutants is blocked in a late function, forms antigenic but
      defective phage particles. The mutation is related to the maturation of phage
      particles. Mutants in the other group also affect a late function, do not form
      antigen, and are assumed to be coat protein mutants. These mutants can be related
      to a series of amber mutants of f2.

PMID- 18611477
TI  - The infection of leafhoppers by western X-disease virus. I. Frequency of
      transmission after injection or acquisition feeding.
AB  - Western X-disease virus (WXV) was transmitted to healthy Colladonus montanus Van
      Duzee by injection of hemolymph or clarified extracts from infected vectors.
      Virus was first transmitted to healthy celery 11-14 days after the insects were
      injected with infectious hemolymph. The inoculativity of vectors injected with
      all inocula reached a peak, then declined rapidly. When tenfold dilutions of
      extract from infected vectors were injected, the position of the transmission
      curve for each dilution with respect to the time scale was a function of virus
      concentration. The latent period in the vector and time of peak transmission were
      therefore extended when dilutions of extract were injected. Transmission curves
      obtained from leafhoppers acquiring WXV by feeding on diseased celery were
      similar to those obtained after injection of a 10(-3) dilution of extract from
      infected vectors. Percentages of insects transmitting WXV in 2- and 4-day
      inoculation access periods could be converted to single-day percentages by
      binomial probability calculations.

PMID- 18611478
TI  - The infection of leafhoppers by Western X-disease .virus II. Fluctuation of virus
      concentration in the hemolymph after injection.
AB  - Transmission curves obtained from Colladonus montanus adults, subinoculated as
      nymphs with hemolymph from vectors previously injected with Western X-disease
      virus (WXV), were used to construct a curve showing relative virus concentration
      in the hemolymph after injection. An increase in WXV titer of approximately 3 log
      units was demonstrated between the 3rd and 21st days after injection. This was
      followed by a 1.5 log unit decline by the 37th day after injection. Transmission
      by the initially injected insects followed a similar course.

PMID- 18611479
TI  - Bentonite aids virus transmission.
AB  - The addition of 0.1-1% bentonite to crude sap of Erigeron glaucus containing
      tomato ringspot virus increased transmission of the virus to bean, but similar
      amounts of bentonite to the same inoculum decreased transmission to cucumber and
      cowpea. Addition of bentonite to crude inoculum of this virus in cucumber, bean,
      and cowpea reduced transmission to cucumber, bean, and cowpea. Bentonite
      decreased transmission to cowpea of cucumber mosaic virus from young cucumber but
      increased transmission from old cucumber and from sugar beet. Bentonite decreased
      transmission of ordinary tobacco necrosis virus from cowpea, bean, or cucumber,
      to cowpea, bean, or cucumber, but increased transmission of the same virus from
      sugar beet to cowpea, bean, or cucumber. Addition of bentonite to the inoculum
      was almost necessary for the transmission of a bentonite-selected mutant of
      tobacco necrosis from one host to another.

PMID- 18611480
TI  - Purification and properties of the pea enation mosaic virus.
AB  - A procedure was developed for the purification of the pea enation mosaic virus
      (PEMV) using differential and rate zonal centrifugation in sucrose density
      gradients. Infectivity and serological data indicated that the highest virus
      concentration occurs in infected peas (Pisum sativum) 10-12 days after mechanical
      inoculation when the plants are grown at 16-22 degrees . Tests with several
      buffer salts at various concentrations and pH values showed that 0.1-0.3 M
      acetate, pH 6.0, was the most suitable for extraction of virus and maintaining
      its infectivity. Approximately 0.3 mg of virus could be obtained per gram of
      infected plant material. Infectivity was found to be associated with two
      nucleoprotein components with sedimentation coefficients of 106 +/- 2 and 122 +/-
      1.5 S, which separated during density gradient centrifugation but which were not
      present in similarly treated healthy tissue. The slower sedimenting component
      appeared to be more infectious than the bulk of the virus material, which
      sedimented somewhat more rapidly. Both components were composed of small
      polyhedral particles approximately 36 micron in diameter as revealed by electron
      microscopy. In addition to the two infectious components, one other which was
      antigenically incomplete and of low molecular weight occurs in freshly extracted
      sap and the supernatant of ultracentrifuged homogenates of infected peas.

PMID- 18611481
TI  - The relation between the C1 region of prophage lambda and propagation of
      bacteriophage T4rII.

PMID- 18611482
TI  - Propagation of Yaba virus in embryonated hen eggs.

PMID- 18611483
TI  - Disruption of type 1 poliovirus under alkaline conditions: role of pH,
      temperature, and sodium dodecyl sulfate (SDS).

PMID- 18611484
TI  - Virus-associated and soluble adenovirus hemagglutinins: differences in antigenic
      specificity.

PMID- 18611485
TI  - Immunofluorescent demonstration of polyoma tumor antigen in lytic infection of
      mouse embryo cells.

PMID- 18611486
TI  - Tobacco mosaic viruslike rods formed by "mixed reconstitution" between MS2
      ribonucleic acid and tobacco mosaic virus protein.

PMID- 18611487
TI  - Heterologous neutralization of adenovirus type 5 at low pH.

PMID- 18611488
TI  - Clonal distribution of hamster cells synthesizing polyoma capsid protein.

PMID- 18611490
TI  - Norfloxacin, the first of a new class of fluoroquinolone antimicrobials,
      revisited.
AB  - Norfloxacin is the first in a series of new 4-quinolones that have been
      introduced into medical practice for the treatment of bacterial infections. This
      totally synthetic compound is a broad spectrum, bactericidal agent that is much
      more potent than the earlier analogs, i.e. nalixidic acid, pipemidic acid,
      cinoxacin, rosoxacin, and flumequine, is less likely to select for resistant
      mutants. While the compound has been used most widely in the treatment of urinary
      tract infections including pyelonephritis and prostatitis, utility has also been
      demonstrated in gastrointestinal and ophthalmological infections, gonorrhea,
      typhoid fever, the typhoid carrier state, as well as in the prophylaxis of
      traveler's diarrhea, biliary tract infections prior to surgery, and gram-negative
      bacillary infections in profoundly neutropenic patients.

PMID- 18611491
TI  - Pefloxacin.

PMID- 18611492
TI  - New strategies for the 1990's: antibacterial therapy.
AB  - Problems of bacterial resistance and a desire to improve the pharmacological
      properties of antimicrobial agents will cause the development of a number of new
      antimicrobial agents in the next few years. Currently there are new beta
      lactamase inhibitor, macrolides, oral cephalosporins, fluoroquinolones, dual
      action cephalosporin-quinolones, and glycopeptides in the initial stages of
      clinical development. These agents will not completely replace the older agents,
      but will provide the physician with even greater flexibility when dealing with
      complicated infections, when switching from parenteral to oral therapy, and when
      resistance is a problem.

PMID- 18611493
TI  - Ofloxacin.

PMID- 18611494
TI  - Ciprofloxacin.

PMID- 18611495
TI  - Pneumocystis carinii pneumonia: the pathogen, the diagnosis and recent advances
      in management.

PMID- 18611496
TI  - Therapy of bacterial meningitis in children.

PMID- 18611497
TI  - Change at different pH levels for better use of antibiotics.

PMID- 18611498
TI  - Antibiotic sensitivity of enteric pathogens in Vietnam.
AB  - The in vitro antimicrobial susceptibilities of 675 common enteropathogenic
      isolates from faecal specimens of patients with diarrhea (E. coli, Shigella,
      Salmonella and V. cholerae), and 568 E. coli isolates from faecal flora of
      healthy persons, which were collected as part of a National antibiotic resistance
      surveillance in Vietnam, were determined. The agar dilution method was used for
      the following nine antibiotics: ampicillin, doxycycline, chloramphenicol,
      gentamicin, nalidixic acid, kanamycin, trimethoprim, trimethoprim in combination
      with sulfamethoxazole (1/20), and sulfisomidin. Gentamicin was the most active of
      the antibiotics tested against all bacterial species with MICs in the range 0.125
      4 mg/l. All strains were susceptible to nalidixic acid (0.125-8 mg/l) and more
      than 90% were susceptible to kanamycin. Among E. coli and Shigella isolates from
      patients the frequencies of resistance to commonly used antibiotics were high:
      ampicillin 73% and 84%, doxycycline 83% and 94%, chloramphenicol 71% and 91%,
      sulfisomidin 82% and 92%, respectively. Resistance to trimethoprin, as well as to
      the combination with sulfamethoxazole was found in 21% and 23%, respectively. The
      frequencies of multiple resistance (resistance to three or more antibiotics) were
      also high (77% and 89%, respectively). Less than 10% of Salmonellae and V.
      cholerae isolates were resistant to ampicillin, sulfisomidin or trimethoprim.
      Among E. coli from healthy people the frequencies of resistance were lower than
      in isolates from patients: ampicillin 23%, doxycycline 40%, chloramphenicol 21%
      and sulfisomidin 34%. However, the same patterns of multiple resistance were
      found in both groups.

PMID- 18611500
TI  - The fluoroquinolones--reappraisal.

PMID- 18611501
TI  - Recent advances in the search for new drugs for treatment of toxoplasmosis.
AB  - Although the combination of pyrimethamine with a sulfonamide is still very
      effective for treatment of toxoplasmosis the use of these two drugs
      immunocompromised individuals, particularly AIDS patienst, often results in a
      remarkable incidence of adverse reactions. There is, therefore, an urgent need
      for alternative drugs and newer therapeutic regimens for treatment of human
      toxoplasmosis. In this review, the in vitro and in vivo activities of a number of
      new drugs and new therapeutic regimens that have shown promising results in
      vartious experimental models for toxoplasmosisared discussed.

PMID- 18611502
TI  - CAPD peritonitis.

PMID- 18611503
TI  - Cefetamet pivoxil: a review of its microbiology, toxicology, pharmacokinetics and
      clinical efficacy.
AB  - Cefetamet pivoxil is an oral, third-generation cephalosporin whose broad spectrum
      of antibacterial activity and favorable pharmacokinetic profile make it
      particularly suitable for the treatment of a wide range of infectious diseases.
      Cefetamet has high in vitro activity against both gram-positive and gram-negative
      bacteria that cause a number of respiratory tract and urinary tract infections.
      These include penicillin-sensitive Streptococcus pneumoniae, Streptococcus spp,
      Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus spp.,
      Klebsiella spp. and Neisseria gonorrhoeae. It is not active against
      staphylococci, enterococci, Pseudomonas spp. or Bacteroides fragilis but does
      inhibit most bile-sensitive (oral) Bacteroides spp. Animal toxicology studies
      indicate that neither cefetamet pivoxil nor the active compound cefetamet have
      significant teratogenic, mutagenic, photogenic or allergenic potential. Cefetamet
      is eliminated unchanged in the urine with a half-life of 2.2 h. Volume of
      distribution approximates the extracellular fluid space (0.3 1/kg), protein
      binding is minima (22%) and oral bioavailability of cefetamet pivoxil is
      approximately 50% when taken with food. No significant drug interactions have
      been noted to date. The efficacy and tolerability of cefetamet pivoxil have been
      evaluated in the treatment of gram-positive and gram-negative infections in
      almost 5,000 patients. In comparative studies, cefetamet pivoxil was at least as
      effective, and in many cases clinically superior, to most currently recommended
      antibiotics for the treatment of urinary tract infections including gonorrhea and
      complicated infections in high risk patients. Efficacy has also been demonstrated
      in acute exacerbations of chronic bronchitis, pneumonia and infections of the
      ear, nose and throat. Clinical trials have shown that a 7 day treatment period
      with cefetamet pivoxil is as effective as a 10 day course of
      phenoxymethylpenicillin in the treatment of pharyngotonsillitis. Cefetamet
      pivoxil has been well-tolerated in clinical trials with only 1.2% of patients on
      standard doses discontinuing therapy prematurely. The most common adverse effects
      are gastrointestinal (diarrhea, nausea, vomiting) which occur in less than 10% of
      patients. Many current antibiotic treatment regimens involve the administration
      of three or more daily doses. However, standard doses of cefetamet pivoxil 500 mg
      twice daily provide unbound plasma concentrations of cefetamet which generally
      exceed the MIC(90) for susceptible organisms throughout the dosing interval and
      have been demonstrated to be clinically effective. This should result in good
      compliance with therapy in out-patients. Dosing regimens for cefetamet pivoxil
      should be adjusted in patients with impaired renal function while standard doses
      can be given to elderly patients and those with liver disease. Standard doses in
      children are 10 mg/kg or alternatively, children may receive a dose reduced in
      proportion to the ratio of their body surface area to that of an adult.

PMID- 18611504
TI  - Nucleic acid analysis of antibiotic resistance.
AB  - The past 15 years the field of molecular biology and especially DNA technology
      has developed rapidly. This did not leave microbiology unaffected. DNA sequencing
      and the use of DNA probes led to new insights in the evolution and spread of
      antibiotic resistance genes. It became clear that resistance determinants often
      show partial homology even when species are not closely related. DNA probes have
      established their value as epidemiological tools and currently efforts are being
      made to introduce them into routine diagnostics.

PMID- 18611505
TI  - Antibiotic resistance in urinary bacteria isolated in central Scotland.
AB  - The levels of antibacterial amongst 991 strains responsible for significant
      bacteriuria, isolated in central Scotland at the end of 1990, have been
      determined by breakpoint sensitivity testing. Overall resistance to the commonly
      used antibacterials for UTI, trimethoprim and ampicillin was 23% and 36%,
      revealing that resistance to these agents in central Scotland had not
      significantly changed over the last ten years. High levels of ampicillin
      resistance have led to the widespread use of amoxicillin in combination with the
      beta-lactamase inhibitor clavulanic acid. The effectiveness of this approach was
      demonstrated by the fact that resistance among these urinary isolates to
      amoxicillin/clavulanic acid was only 6%. More detailed examination of Escherichia
      coli isolates, which were ampicillin-resistant, revealed that the addition of
      clavulanic acid restored sensitivity in 97.5% of the strains.

PMID- 18611506
TI  - Prevention and treatment of infections in cystic fibrosis.

PMID- 18611507
TI  - Enterococcus faecium resistant to ampicillin and gentamicin.
AB  - Thirty ampicillin-resistant enterococci were isolated from clinical specimens at
      our institution, 28 of these over a six month period. All were identified as
      Enterococcus faecium with an MIC(90) to ampicillin ond penicillin of 32 and 128
      mug/ml, respectively. These isolates were also resistant to imipenem, ampicillin
      sulbactam, and amoxicillin-clavulanic acid, but susceptible to vancomycin. Only
      10%% were resistant to gentamicin at 2 000 mug/ml, but bactericidad synergy could
      not be demonstrated against any of these isolates using the combination of
      gentamicin added to either penicillin or vancomycin. No beta-lactamase activity
      was detected by the nitrocephin test, or by the addition of clavulanic acid or
      sulbactam. Plasmid analysis revealed a band common to 29 of 30 ampicillin
      resistant E. faecium, which was not present in two ampicillin-sensitive E.
      faecium or in any of twenty E. faecalis. The limited number of options available
      to treat these isolates of E. faecium simultaneously resistant to multiple
      antibiotics and resistant to the bactericidad synergy of gentamicin underscores
      the need to develop new strategies in the prevention and treatment of
      enterococcal infections.

PMID- 18611508
TI  - Oral pseudomonas aeruginosa immunization enhances survival in mice subsequently
      burned and infected with P. aeruginosa.
AB  - Mice fed 0 serotype-specific strains of P. aeruginosa for two weeks, had
      increased titers of IgM but not IgG antibodies to the strains fed. Immunized
      mice, burned and infected with P. aeruginosa, showed significant 0 serotype
      specific enhanced survival. Survival of mice fed several 0 serotype-specific
      strains simultaneously increased when these mice were burned and infected with P.
      aeruginosa homologous to those fed except when a high exotoxin A producing strain
      was used. Mice fed purified exotoxin A showed an increased LD(50) when injected
      with graded toxin doses. Feeding both 0 serotype-specific P. aeruginosa plus
      exotocin A increased survival even with burn and infection using the high toxin
      producing strain. We conclude that feeding P. aeruginosa antigens provides
      successful immunization which avoids the effects of parental adminstration.

PMID- 18611509
TI  - Home intravenous antibiotic therapy.
AB  - Concern regarding the soaring costs of in-hospital treatment has stimulated
      interest in providing alternatives when patients no longer need careful
      observation and daily nursing care. To facilitate ongoing intravenous antibiotic
      therapy for selected patients, home or outpatient intravenous therapy programs
      have been developed. Such therapies require a team approach with an emphasis on
      patient selection criteria, and educational strategies, as well as careful follow
      up. It is likely that in the near future more intravenous anti-infective programs
      will be tailored to the infectious complications of the acquired immune
      deficiency syndrome than for the conditions. The increasing number of effective
      new oral drugs will undoubtedly reduce the need for intravenous therapy for
      specific infections such as septic arthritis, osteomyelitis, urinary tract
      infections and pneumonia.

PMID- 18611510
TI  - Effect of administration of diethylcarbamazine on experimental bacterial and
      fungal infections in mice.
AB  - Other researchers have found that diethylcarbamazine (DEC) is effective treatment
      for filariasis despite a lack of demonstrated in vitro antifilarial activity. The
      results of our previous investigations using feline and murine leukemia virus
      models encouraged us to investigate the use of DEC with other infections. In the
      current experiments, DEC treatmentS was associated with (a) increased survival
      and decreased brain Streptococcus pneumoniae levels following S. pneumoniae
      challenge in previously immunized mice; (b) increased serum antibody levels to S.
      pneumoniae, Escherichia coli, and Haemophilus influenzae following inoculation of
      live bacteria; and (c) lower brain fungal levels following intravenous injection
      of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans
      organisms, and lower brain and kidney levels of Candida albicans following
      intravenous injection of increasing numbers of C. albicans.

PMID- 18611511
TI  - Lomefloxacin: a once-a-day quinolone.

PMID- 18611512
TI  - Quinolone pharmacokinetics.
AB  - Fluoroquinolones have broad antibacterial spectra and are active against most
      Gram-negative and many Gram-positive species. They exhibit excellent oral
      bioavailability, extensive tissue penetration, low protein binding, and a long
      elimination half-life. This review compares and contrasts the pharmakonetics of
      some quinolone antibiotics - especially pefloxacin, ciprofloxacin, enoxacin,
      norfloxacin, ofloxacin, fleroxacin and lomefloxacin - in terms of their
      adsorption, distribution, metabolism, elimination, and interactions with other
      drugs and with food. In addition, the pharmacokinetics of these agents in the
      elderly and in patients with renal or hepatic impairment is discussed. The
      fluoroquinolones are established as a major class of antibiotics in the treatment
      of infections but pharmacokinetics factors should be considered when deciding on
      the most appropriate of these agents to use in individual patients.

PMID- 18611513
TI  - Comparative study of the in vitro activity of lomefloxacin versus lomefloxacin
      combined with metronidazole versus lomefloxacin in combination with
      amoxicillin/clavulanic acid against Chlamydia trachomatis.
AB  - The role of Chlamydia trachomatis in both acute and chronic salpingitis is well
      known but other bacterial species can act symbiotically with this organism to
      enhance pathogenicity. The advent of the fluoroquinolones-with their very broad
      spectrum of activity particularly on chlamydial species, gonococci and the
      Enterobacteriaceae-hase raised the possibility that new antibiotic combinations
      may be used in the treatment of salpingitis. Since Chlamydia trachomatis is an
      intracellular pathogen, we devised a cell culture system to evaluate the efficacy
      (or any antagonistic effects) of lomefloxacin in combination with metronidazole
      and lomefloxacin in combination with amoxicillin/clavulanic acid. Our study
      showed that there appeared to be no inoculum effect. In addition, we found no in
      vitro antagonism between lomefloxacin and metronidazole or lomefloxacin and
      amoxicillin/clavullanic acid against Chlamydia trachomatis. These results justify
      the use of these combinations in vivo in patients infected with Chlamydia
      trachomatis infections.

PMID- 18611514
TI  - Fluoroquinolone resistance in the hospital versus outpatient setting.
AB  - The Lomefloxacin International Surveillance Trial (LIST) is an in vitro testing
      program specifically designed to assess the antimicrobial activity of
      lomefloxacin against a wide range of clinical isolates from hospitals, clinics,
      and laboratories worldwide. Lomefloxacin was used as a representative quinolone
      to assess susceptibility patterns of fresh clinical isolates for new
      fluoroquinolones. Between June 1989 and December 1990, hospitals and clinics in
      France contributed zone-diameter data (5 mug disk) on approximately 45 000
      clinical isolates. Data were collected by a processing center in the USA and were
      analyzed to identify susceptibility patterns by region and by country in addition
      to identifying trends in high-grade fluoroquinolone resistance. This analysis
      showed that an unusual and widespread pattern of fluoroquinolone resistance was
      observed for isolates tested at tertiary-care centers in France. In order to
      assess whether high levels of fluoroquinolone usage in these centers might be
      responsible for this level of resistance, a group of six French Community Clinics
      was added to the testing program in 1990. From May 1990 until April 1991, these
      clinics contributed data on almost 4500 strains to the testing program. In most
      cases, there was little or no difference between susceptibility patterns obtained
      in French Community Clinics and University Hospitals. The only statistically
      significant difference noted was for Staphylococcus aureus: only 70% of French
      University Hospital strains were susceptible to lomefloxacin compared with 92% of
      Community Clinic strains (p<0.05). This result is in agreement with other studies
      of new fluoroquinolones carried out in the USA and worldwide. Many of the
      fluoroquinolone-resistant strains of Staphylococcus aureus were also resistant to
      methicillin and other anti-bacterial drugs.

PMID- 18611515
TI  - Quinolones in the treatment of uncomplicated urinary tract infections.
AB  - In comparative clinical studies the quinolones have been shown to be effective in
      a short-course (3-5 days) or a single dose therapy in uncomplicated urinary tract
      infections. Comparative clinical trials of single dose therapy with the
      fluoroquinolones and trimethoprim or co-trimoxazole (trimethoprim/
      sulfamethoxazole) for acute bacterial cystitis have shown equivalent efficacy.
      Studies on the use of quinolones for the treatment of uncomplicated acute
      pyelonephritis have also been reviewed. The results from several comparative
      trials which compared the fluoroquinolones with netilmicin, co-trimoxazole,
      cefadroxil, or ceftazidime have been comparable. Some of the fluoroquinolones can
      be administered in parenteral and oral forms enabling the patient to be
      discharged from hospital earlier, a more cost-effective option. The
      fluoroquinolones, in particular norfloxacin, have also been shown to be effective
      as prophylactic agents for patients with recurrent symptomatic urinary tract
      infections. The optimal dosage and length of prophylactic treatment have not yet
      been clearly defined.

PMID- 18611516
TI  - A multicenter study of lomefloxacin versus ciprofloxacin in the treatment of
      complicated urinary tract infections.
AB  - Lomefloxacin is a new difluorinated quinolone antimicrobial agent with broad
      antibacterial activity and a long half-life which allows once-daily dosing. A
      multicenter, randomized trial was conducted to compare the safety and efficacy of
      once-daily oral lomefloxacin with twice-daily oral ciprofloxacin in the treatment
      of complicated urinary tract infections (UTIs). All 203 patients enrolled in the
      study had significant bacteriuria of - 10(5) colony-forming units/ml (CFU/ml) and
      clinical signs and symptoms of UTI such as dysuria, frequency, urgency, pain, or
      hematuria. Patients were randomized to receive either 400 mg lomefloxacin once
      daily (n = 101) or 250 mg ciprofloxacin twice daily (n = 102). The predominant
      baseline pathogen isolated from the patients in both groups was Escherichia coli.
      At the third visit (5-9 days post-treatment), 97.8% of patients in the
      lomefloxacin group and 96.8% in the ciprofloxacin group showed satisfactory
      bacteriologic results. Clinical success was achieved in 98.9% of patients in both
      treatment groups and there were no statistically significant differences between
      the two groups. Both drug regimens were well tolerated and no patient
      discontinued treatment due to adverse events. It was concluded that once-daily
      lemofloxacin was as effective as twice-daily ciprofloxacin in patients with
      complicated UTIs.

PMID- 18611517
TI  - Lomefloxacin versus norfloxacin versus ciprofloxacin in the treatment of
      complicated urinary tract infections.
AB  - The safety and efficacy of lomefloxacin 400 mg once daily in the treatment of
      complicated urinary tract infections (UTIs) were assessed in one open, non
      comparative study (n = 101) and three comparative, multicenter studies - two
      versus norfloxacin 400 mg b.i.d. (n = 326) and one versus ciprofloxacin 500 mg
      b.i.d. (n = 150). The antibiotics were administered orally for 7-14 days. Safety
      was assessed by physical examination, laboratory tests and questioning of
      patients. Patients had initial counts of - 10(5) colony-forming units/ml (CFU/ml)
      of pathogens which were susceptible to the study drugs. Clinical and
      bacteriologic outcome were assessed 5-9 days post-treatment. Success (cure or
      improvement of presenting signs and symptoms) was achieved in approximately 90%
      of the patients, irrespective of the drug therapy used. Eradication of baseline
      pathogens was achieved with lomefloxacin in 79.4% (50 63 ) of evaluable patients
      in the open study, in 91.3% (84 92 ) of patients in the norfloxacin comparative
      studies and in 97.2% (70 72 ) of evaluable patients in the ciprofloxacin
      comparative study. Eradication was achieved in 78.4% (76 97 ) of norfloxacin
      treated evaluable patients and in 95.7% (67 70 ) of evaluable patiens treated
      with ciprofloxacin. The results obtained with lomefloxacin were statistically
      significantly better than those obtained with norfloxacin (p = 0.015), but
      equivalent to those with ciprofloxacin (p = 0.626). Superinfections occurred in
      5.3% (12 227 ) of evaluable patients treated with lomefloxacin and in 9.3% (9 97
      ) treated with norfloxacin. There were no superinfections in the 70 evaluable
      patients treated with ciprofloxacin. Adverse events (mainly gastrointestinal)
      which were probably drug-related occurred in 6.7% (23 341 ) of patients treated
      with lomefloxacin, in 3.1% (5 160 ) pateints treated with norfloxacin and in 6.7%
      (5 75 ) of patients treated with ciprofloxacin. A once-daily regimen of
      lomefloxacin 400 mg was found to be safe and produced superior or equivalent
      eradication rates of norfloxacin and ciprofloxacin, respectively.

PMID- 18611518
TI  - Lomefloxacin versus amoxicillin in the treatment of acute exacerbations of
      chronic bronchitis: results of multinational studies.
AB  - The results of two large, multicenter studies comparing the safety and efficacy
      of lomefloxacin (400 mg administered orally once daily) and amoxicillin (500 mg
      administered orally three times daily) in adult patients with acute exacerbations
      of chronic bronchitis caused predominantly by Gram-negative pathogens have been
      combined. The studies were both randomized and blinded. One study enrolled 127
      patients in 12 centers in Belgium; the second enrolled 510 patients in 52 centers
      in ten countries. The protocols were essentially identical, whicl allowed data to
      be pooled. A total of 253 lomefloxacin-treated patients and 254 amoxicillin
      treated patients were considered evaluable. Both groups were well matched in
      terms of age, gender, and severity of presenting signs and symptoms. The most
      common pathogens in both treatment groups were Haemophilus influenzae,
      Pseudomonas aeruginosa, Streptococcus pneumoniae, Moraxella (Branhamella)
      catarrhalis, and Klebsiella pneumoniae. Two to four days after the conclusion of
      treatment, bacterial eradication rates were 85.4% for lomefloxacin-treated
      patients and 75.2% for patients receiving amoxicillin (p = 0.004). The clinical
      success rate (total of evaluable patients either cured or improved) 2-4 days
      after the conclusion of treatment for the lomefloxacin group was 90.9%, and for
      amoxicillin was 82.3% (p = 0.005). The incidence of adverse events was similar in
      both treatment groups, and no interactions were noted in those patients in both
      groups who received concomitant theophylline. In these studies, lomefloxacin
      administered once daily was superior to amoxicillin given three times daily to
      patients with acute bacterial exacerbations of chronic bronchitis caused
      predominantly by Gram-negative pathogens.

PMID- 18611519
TI  - Comparison of the safety and efficacy of lomefloxacin and amoxicillin in the
      treatment of acute exacerbations of chronic bronchitis: Results from a Latin
      American multicenter study.
AB  - The aim of this study was to compare the safety and efficacy of lomefloxacin, a
      new difluornated quinolone, with those of amoxicillin in the treatment of acute
      exacerbations of chronic bronchitis caused by Gram-negative bacteria. The study
      was conducted as a multicenter, randomized, single-blind comparison in four
      countries (Argentina, Colombia, Mexico and Venezuela). In total, 163 evaluable
      patients were assessed-82 in the lomefloxacin group and 81 in the amoxicillin
      group. Patients received oral therapy with either 40 mg lomefloxacin once daily
      or 500 mg amoxicillin three times daily for 10 days. The most frequent bacterial
      pathogens isolated included: Haemophilus influenzae, Moraxella catarrhalis,
      Pseudomonas aeruginosa and Klebsiella pneumoniae. The overall clinical success
      rates (cure plus improvement) were 93.9% in the lomefloxacin group and 81.5% in
      the amoxicillin group. The eradication rate was 81.7% in the lomefloxacin group
      and 75.3% in the amoxicillin group. Most of the clinical and bacteriological
      failures in both groups were associated with P. aeruginosa in baseline sputum
      cultures. In conclusion, once-daily lomefloxacin is a safe and effective
      treatment for acute exacerbations of chronic bronchitis caused by Gram-negative
      pathogens.

PMID- 18611520
TI  - Safety and efficacy of lomefloxacin and cefaclor in the treatment of skin and
      skin structure infections.
AB  - The purpose of this study was to compare the safety and efficacy of lomefloxacin
      with that of cefaclor in the treatment of adult secondary bacterial skin and skin
      structure infections. The study was conducted as a randomized, single-blind
      comparison. Eighty patients enrolled in the study, of which 74 were evaluable: 37
      patients in the lomefloxacin group and 37 in the cefaclor group. Patients
      received either 400 mg of lomefloxacin orally once daily or 250 mg of cefaclor
      orally three times daily for 12 days. The most frequent pathogens isolated
      included Staphylococcus aureus, Streptococcus pyogenes, coagulase-negative
      staphylococci, and Escherichia coli. The clinical response was similar in both
      groups (89.1%). The bacteriologic eradication rate was 100% in the lomefloxacin
      group and 94.5% in the cefaclor group. Adverse events were minimal. Once-daily
      lomefloxacin is a safe and effective treatment for secondary bacterial skin and
      skin structure infections caused by susceptible pathogens.

PMID- 18611521
TI  - Lomefloxacin versus trimethoprim/sulfamethoxazole in the treatment of adults with
      acute bacterial diarrhea.
AB  - This study compared the efficacy and safety of lomefloxacin with that of
      trimethoprim/sulfamethoxazole (TMP/SMX) in the treatment of adult patients with
      acute diarrhea of bacterial etiology. Two centers enrolled a total of 133
      patients; 99 (74%) presented with severe symptoms. The patients were randomized
      to receive either lomefloxacin 400 mg once daily (n=68) or TMP/SMX 160/800 mg
      twice daily (n=65) for five days. Bacteriologic success was achieved in 89.5% of
      evaluation lomefloxacin-treated patients and in 97.5% of patients treated with
      TMP/SMX. Clinical success was achieved in 100% and 97.5% of patients in the two
      treatment groups, respectively. The predominant organisms isolated in both groups
      at baseline, i.e. Shigella flexneri, Vibrio parahaemolyticus, and Salmonella
      Group D, were eradicated in all patients. Campylobacter jejuni was isolated at
      baseline in four patients in the lomefloxacin group but in none randomized to
      receive TMP/SMX; this organism persisted in three patients. Adverse events were
      experienced by 14 (23%) of the lomefloxacin-treated patients and by 18 (30%) of
      the TMP/SMX-treated patients. All adverse events reported were mild or moderate
      in severity and their distribution was similar in both groups. The results of
      this study show that lomefloxacin 400 mg once daily is as effective as TMP/SMX
      160/800 mg twice daily and suggest that lomefloxacin is a promising new quinolone
      for the treatment of bacterial diarrhea.

PMID- 18611522
TI  - A worldwide clinical overview of lomefloxacin, a once-daily fluoroquinolone.
AB  - Lomefloxacin, an orally active difluorinated quinolone, is active against a wide
      variety of clinically relevant Gram-negative and Gram-positive organisms. A
      totoal of 3387 evaluable patients received (both complicated and uncomplicated),
      acute exacerbations of chronic bronchitis, acute bacterial diarrhea, skin and
      skin structure infections, or for prophylaxis during urinary tract surgery or
      instrumentation. In these studies lomefloxacin was compared with oral
      norfloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole, amoxicillin and
      cefaclor, and the parenteral agents cefotaxime and cefuroxime. Once-daily oral
      administration of lomefloxacin was either equally effective or statistically
      significantly superior in clinical and/or bacteriologic efficacy to comparative
      agents that were administered two or three times per day (except for prophylaxis
      studies, in which single doses of each antibiotic were administered
      preoperatively). The safely of lomefloxacin was assessed in 3246 patients and
      subjects. Most adverse events were mild to moderate in severity. In general, the
      incidence of adverse events for patients and subjects receiving lomefloxacin was
      comparable to that observed in patients treated with comparative drugs. The
      incidence of adverse events in elderly patients was similar to that observed in
      younger patients. Concurrent administratopm of the ophylline did not increase the
      incidence of adverse events. The most common adverse events were related tothe
      gastrointestinal tract (nausea), the skin and appendages (photosensitivity) and
      the central nervous system (dizziness). Lomefloxacin, administered orally once
      daily, is effective and well tolerated in patients with a variety of infections
      of bacterial origin.

PMID- 18611523
TI  - The osmotic pressure of the maintenance medium and reproduction of poliovirus.
AB  - When the osmotic pressure of the maintenance medium is decreased, poliovirus
      reproduction is inhibited. Poliovirus strains may vary in their sensitivity to
      the effect of hypotonic solutions. Mutants have been selected (designated as osm
      mutants) the reproduction of which is characterized by particularly high
      resistance to media with reduced osmotic pressure. Initial stages of the virus
      cell interaction proceed at similar rates in physiologic and hypotonic solutions.
      Reactions sensitive to hypotonic solutions take place in the second half of the
      latent period and during the stage of virus maturation. The multiplication of
      viruses in moderately hypotonic solutions exhibits a marked dependence upon the
      temperature and the presence of cystine in the medium, even though these factors
      have relatively small influence upon the reproduction of the viruses in isotonic
      solutions. Despite complete cessation of the production of infectious virus in
      certain hypotonic media, there is a considerable synthesis of virus-induced RNA.
      At least some of the RNA produced under these conditions is infectious. With a
      further decrease of the osmotic pressure of the medium the synthesis of the viral
      RNA is inhibited. Some possible explanations of the observed facts are briefly
      discussed.

PMID- 18611524
TI  - Relation between ectodesmata and infection of tomato roots by 14C-labeled tobacco
      mosaic virus.
AB  - The occurrence of ectodesmata in roots of Lycopersicon esculentum Mill, cultivar
      'Potentaat' could be demonstrated after suitable fixation and staining. Roots of
      tomato plants grown in soil or in liquid medium and excised roots cultivated in
      vitro were fixed and stained after inoculation with 14C-labeled TMV and covered
      with photographic emulsion Ilford L-4. After development, the location of beta
      tracks was determined under a light microscope. Accumulations of radioactive
      virus material were often found in the neighborhood of ectodesmata at the root
      tip and in root hairs. A relation was found between the presence of ectodesmata
      and the susceptibility of roots to virus infection.

PMID- 18611525
TI  - Localization and recovery of lettuce necrotic yellows virus from xylem tissues of
      Nicotiana glutinosa.

PMID- 18611526
TI  - ARI 1: beta-lactamase-mediated imipenem resistance in Acinetobacter baumannii.
AB  - A strain of Acinetobacter baumannii 6B92 isolated from the blood culture of a
      patient at the Edinburgh Royal Infirmary i 1985 was found to be resistant to
      imipenem, all classes of cephalosporins and penicillins. Extraction of the
      soluble proteins of the cell and isoelectric focusing revealed the presence of
      two beta-lactamases: a chromosomal cephalosporinase of high pI (> pI 9.0) and a
      novel beta-lactomase of pI 6.65 named ARI 1 (Acinetobacter resistant to
      imipenem). Despite the fact that original clinical isolate could be 'cured' of
      its resistance to imipenem and penicillins by growing in the presence of ethidium
      bromide with the concurrent loss of the ARI 1 enzymes, no resistance plasmid was
      visualised or transferred. The ARI 1 beta-lactamase hydrolysed penicillin,
      ampicillin and cephaloridine slowly during enzyme assay but inactivation of
      imipenem could only be demonstrated by microbiological means. The molecular size
      of the ARI 1 enzyme was 23 kDa and it was not inhibited by EDTA, p-CMB, or
      clavulanate.

PMID- 18611527
TI  - The incidences of resistance to cephalosporins and fluorinated 4-quinolones in
      similar strains isolated in Glasgow and Edinburgh.
AB  - Bacterial sensitivity to cefuroxime, ceftazidime, cefotaxime, ciprofloxacin and
      ofloxacin was determined for 1386 urinary and bacteraemia isolates from Glasgow
      and Edinburgh to detemine the impact of these antibacterials on the development
      of resistance. The MIC(50) and MIC(90) values were determined for each species or
      genus. Cefuroxine was the least effective antibacterial drug and cefotaxime was
      the most potent cephalosporin, but it rarely matched the efficacy of the 4
      quinolones. There was little difference in the sensitivities of Gram-negative
      bacteria from Edinburgh of Glasgow but Gram-positive bacteria isolated in Glasgow
      were usually more resistant. There has been no significant emergence of resistant
      Gram-negative bacteria even amongst the Pseudomonas spp.; however, the proportion
      of Gram-positive bacteria resistant to these drugs is higher in Scotland than
      elsewhere.

PMID- 18611528
TI  - Immunoprophylaxis and immunotherapy: role in the prevention and treatment of
      repiratory syncytial virus.
AB  - It is now apparent that neutralizing antibody may play an important role in
      ameliorating RSV lower repiratory tract illness. At the present time
      immunoprophylaxis and immunotherapy with polyclonal antibodies show the most
      promise in the prevention and treatment of RSV illness. Several questions
      remained to be answered. These include the practical application of IGIV in
      prevention and treatment of RSV illness. Intravenous lines are often difficult to
      place and maintain. With the further development of polyclonal or monoclonal
      antibodies it may be possible to immunize prospective donors and boost their anti
      RSV titers to the degree that a hyper-immune IGIV with sufficient antibody to be
      given intramuscularly could be produced. The role for RSV-specific monoclonal
      antibodies for disease prevention or treatment must be defined as well as the
      appropriatee viral epitopes to target. In the absence of a safe and effective
      vaccine, it is clear that, despite these questions passive immunotherapy and
      immunoprophylaxis offers the greatest hope for the prevention and treatment of
      RSV disease in high risk infants and children.

PMID- 18611529
TI  - Post-antibiotic effects of miocamycin, roxithromycin and erythromycin on Gram
      positive cocci.
AB  - The 16-membered macrolide miocamycin (MOM) has been compared with the 14-membered
      compounds erythromycin and roxithromycin in terms of causing post-antibiotic
      effects (PAE). Five strains of methicillin-resistant Staphylococcus aureus, 3
      Streptococcus pyogenes, 3 S. agalactiae and 3 enterococci, of differing
      phenotypes of resistance to erythromycin, were tested. PAE were measured
      follwonig exposure of cocci to 1 x, 3 x and 10 x MICs of each antibiotic. Against
      the staphylococci and group A streptococci the three macrolides gave similar
      results, PAE of 1- h at 1 x MIC, 2-4 h at 3 x MIC and > 4 h at 10 x MIC being
      observed. For group B streptococci and the only erythromycin-sensitive
      enterococcus tested, PAE due to MOM were at least double those due to
      erythromycin or roxithromycin, at each concentration tested. MOM produced
      significant PAE for the strains that were inducibly resistant to erythromycin and
      roxithromycin.

PMID- 18611530
TI  - Cellular uptake and activity of rufloxacin in different cell types and
      professional phagocytic cells.
AB  - The penetration of the new quinolene rufloxacin into human professional
      phagocytic cells and different cell types was determined. The intracellular
      distribution was demonstrated in all cells studied. At 4 degrees C the transport
      of rufloxacin was reduced. An intracellular dose-dependent activity was
      demonstrated for rufloxacin in monocytes and granulocytes infected with E. coli
      and S. aureus. In all the experiments rufloxacin was able to eliminate all
      intracellular bacteria.

PMID- 18611531
TI  - Comparison of the intrabacterial Na+,K(+)-ratio and multiplication in the mouse
      foot pad as measures of the proportion of viable Myobacterium lepraemurium.
AB  - Drug are generally screened for activity against Mycobacterium leprae by
      administration to M. leprae-infected mice, and the efficacy of a chemotherapeutic
      regimen is assessed by inoculating mice with M. leprae recovered from the skin
      biopsy specimens obtained at intervals during treatment. Both methods are
      expensive and time consuming. Although a number of methods has been proposed for
      the rapid distinction between viable and non viable M. leprae, none has found
      wide acceptance. Earlier work had shown that the ratios of the intrabacterial
      concentrations of Na(+) and K(+) (Na(+),K(+)-ratio) of individual bacterial
      cells, measured by means of laser microprobe mass analysis, are a sensitive
      indicator of the viability of cultivable organisms. Assuming that the maximal
      value (the "limiting value") of the Na(+),K(+)-ratio of viable cultivable
      organisms is valid for non-cultivable species, the degree of correspondence
      between intrabacterial Na(+),K(+)-ratios of M. lepraemurium after treatment in
      vivo with isoniazid, streptomycin and clofazimine, and the ability of these
      organisms to multiply in mice were examined. A linear relationship between the
      proportion of viable organisms, calculated from the limiting value of the
      Na(+),K(+)-ratio, and that calculated from ID50 was found, suggesting that, at
      least for M. lepraemurium, the intrabacterial Na(+),K(+)-ratio predicts the
      effect of drugs measured by the much more demanding technique of mouse
      inoculation.

PMID- 18611532
TI  - The role of antibiotics in platelet dysfunction and coagulopathy.

PMID- 18611534
TI  - Cefaclor.

PMID- 18611533
TI  - Fluoroquinolones: mechanisms of action and resistance.
AB  - The mechanism of action and the mechanism of resistance of the 4-quinolones are
      complex and poorly understood. The first barrier these molecules must cross is
      the bacterial outer membrane. In gram-negative species, 4-quinolones pass through
      either the porins or lipopolysaccharides (or both) depending on their chemical
      nature. The cellular target is the DNA of the bacterial chromosome. 4-Quinolones
      mainly modify the activity of topoisomerase II or DNA gyrase, but also that of
      topoisomerase I and IV. Any damage to the bacterial genome will induce a stress
      response which consists in the SOS response, chaperonin synthesis or the
      generation of oxygen free radicals. Peptidoglycan synthesis is also modified, as
      shown by the inhibition of PBP(3) activity. Mechanism of resistance involves
      mutations on gyrA and gyrB genes. gyrA Mutations on the chromosome are
      responsible for a high level of resistance due to a modification of the A subunit
      of DNA gyrase, mutations on gyrB gene are responsible for a low level of
      resistance; the combination of both mutations leads to a high level of
      resistance. Other mutations are responsible for increasing the MIC, such as a
      norA mutation in S. aureus. The antibacterial activity of the various molecules
      is different and, as a result, there is not a single mechanism of action or
      resistance, but rather a common trunk on which additional mechanisms are grafted.

PMID- 18611535
TI  - Fleroxacin: a review of its chemistry, microbiology, toxicology,
      pharmacokinetics, clinical efficacy and safety.

PMID- 18611536
TI  - Successful treatment of chronic disseminated candidiasis with high-dose
      fluconazole in a child with acute myelo-monocytic leukemia.
AB  - A 6-year-old boy with acute myelo-monocytic leukemia [French-American-British
      classification, M4 (Bennett et al., Br J Haematol 1976; 33: 451-458)] developed
      chronic disseminated candidiasis (CDC) in a phase of remission induction
      chemotherapy. The diagnosis was made based on the histological examination of the
      biopsy specimen of the liver that showed invasion of Candida. High-dose
      fluconazole (FCZ) therapy (up to 23.5 mg/kg/day) was given effectively and
      without significant side effect over a period of 15 months. Pharmacokinetic
      analysis revealed that FCZ showed one or two compartment model. Administration of
      12 mg/kg/day of the drug showed that t (1 2 ) were 11.5 and 16.1 h, respectively.
      We would suggest that if lesser doses are ineffective in eradicating invasive
      fungal infection, dose escalation of FCZ was possible up to a single
      administration of 20 mg/kg daily in children.

PMID- 18611537
TI  - Effect of administration of diethylcarbamazine with and without fluconazole on
      experimental fungal infections in mice.
AB  - Other researchers have found that diethylcarbamazine (DEC) is effective treatment
      for filariasis despite a lack of demonstrated in vitro antifilarial activity. The
      results of our previous investigations using feline and murine leukemia virus
      models encouraged us to investigate the use of DEC with other infections. In our
      current experiments, DEC treatment was associated with lower brain fungal burden
      in fluconazole-treated mice following intravenous injection of Aspergillus
      fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower
      brain and kidney levels of Candida albicans following intravenous injection of
      increasing numbers of C. albicans. Further investigation of combined DEC and
      fluconazole treatment of fungal infections is warranted.

PMID- 18611538
TI  - LC-9018 treatment enhances survival in gram-negative burn wound sepsis.
AB  - Mice pretreated with the LC-9018 showed enhanced survival compared to controls
      when burned and infected with P. aeruginosa and K. pneumoniae strains. Burned
      skin quantitative bacterial counts in LC-9018 treated and controls were similar
      but kidney and liver counts of treated mice were significantly lower. Increased
      peritoneal cell counts in LC-9018 treated groups suggested enhanced survival and
      lower organ counts resulted from increased microbial clearance. Survival in LC
      9018 pretreated P. aeruginosa infected burned mice was reduced in neutropenic or
      macrophage blockaded mice which supported this hypothesis. Burned mice treated
      with LC-9018 at times postburn but pre-P. aeruginosa infection showed
      significantly enhanced survival. Thus LC-9018 treatment might be useful for
      increasing survival from burn wound sepsis and further investigation is
      warranted.

PMID- 18611539
TI  - In vitro activity of macrolides and lincosamides against oral streptococci: a
      therapeutic alternative in prophylaxis for infective endocarditis.
AB  - Susceptibility to macrolides and lincosamides was tested in a total of 446
      strains of oral streptococci belonging to eleven species, all isolated from
      dental plaque and/or saliva in 1991. Minimum inhibitory concentrations (MIC) were
      determined by the double serial dilutions method in agar. Clindamycin was the
      most effective antibiotic against all species tested. The results of nearly all
      parameters (range, mean, MIC(50), MIC(90)) in all species showed erythromycin to
      be less effective than josamycin, making the latter antibiotic a possible
      alternative to erythromycin in prophylaxis for infective endocarditis caused by
      oral streptococci, not only in patients allergic to penicillin, but also in all
      patients with low-risk lesions, who will be treated with low-risk dental
      procedures. In these latter patients, antibiotic prophylaxis may be indicated if,
      after careful evaluation of the individual's situation, no other alternatives are
      available.

PMID- 18611540
TI  - Effects of low, subinhibitory concentrations of antibiotics on expression of a
      virulence gene cluster of pathogenic Escherichia coli by using a wild-type gene
      fusion.
AB  - S fimbrial adhesins (Sfa) represent virulence factors of E. coli wild-type
      strains causing urinary tract infections and meningitis of the new born. In order
      to determine the influence of subinhibitory concentration of antibiotics on the
      expression of the sfa gene cluster, a wild-type strain carrying the lacZ gene,
      coding for the enzyme beta-galactosidase fused to the sfa determinant was used.
      The expression of lacZ which was under the control of the sfa wild-type
      promoters, was now equivalent to the sfa gene expression of wild-type strain 536.
      With this strain the influence of subinhibitory concentrations of 28 antibiotics
      on the expression of the sfa determinant was studied. The expression was strongly
      suppressed by a treatment of the wild-type fusion strain by aztreonam,
      gentamicin, clindamycin and trimethoprim; the latter had a dramatic effect on sfa
      expression. It was further shown for clindamycin and trimethoprim that the
      reduction of sfa gene expression was dependent on the concentration of the
      antibiotics. In contrast imipinem, amphotericin B and rifampicin weakly
      stimulated sfa expression. We conclude that gene fusions between virulence
      associated loci and indicator genes in wild-type pathogens are useful to study
      virulence modulation due to subinhibitory concentration of antibiotics on the
      genetic level.

PMID- 18611541
TI  - Cefixime.

PMID- 18611542
TI  - Clostridium difficile-associated diarrhea and colitis: pathogenesis and therapy.

PMID- 18611543
TI  - Diarrhea in intensive care: diagnosis and treatment.
AB  - Diarrhea is a common complication in critically ill patients. The use of ready-to
      use sterile formulas, disposable feeding lines, and flow regulated pumps should
      decrease the frequency of diarrhea due to enteral nutrition. Antimicrobial agents
      are an important cause of diarrhea, because they modify the digestive flora and
      may induce Clostridium difficile colitis. Occurrence of diarrhea is also
      correlated with several factors reflecting the severity of the underlying
      disease, such as shock and sepsis. Treatment of diarrhea includes rehydratation,
      agents that delay transit, restoration of a normal flora, treatment of a specific
      cause and of the underlying disease.

PMID- 18611544
TI  - Controversies on pharmacokinetics of fluoroquinolones in elderly patients.
AB  - Antibiotic treatment of elderly patients poses several problems including
      uncertainty about the dosage of fluoroquinolones. Huge interindividual
      differences characterise the pharmacokinetics of fluoroquinolones, and these
      differences may surpass several times the age-related average alterations. No
      routine dose adjustment can be recommended, since the outcome of treatment might
      be jeopardized by an unwarranted dose reduction. At present, creatinine clearance
      is the best guide for dose adjustment, but in the case of severe infection, even
      monitoring of serum concentration might be necessary. Individual dosage is
      required for elderly patients, taking into consideration the severity and site of
      infection, the general condition of the patient and the sensitivity of the
      pathogen.

PMID- 18611545
TI  - Inhibition of two imidazole antimycotics, eberconazole and clotrimazole, by
      different components of Candida albicans serotype B membrane protoplasts.
AB  - The inhibitory activity of different components from Candida albicans membrane
      protoplasts against clotrimazole and eberconazole was studied. The phospholipid
      fraction had the most inhibitory activity and the antimycotic activity of
      eberconazole was more affected than that of clotrimazole.

PMID- 18611546
TI  - Penetration of carumonam into the pleural fluid: comparison of intravenous bolus
      and constant infusion in rats with experimentally induced pleurisy.
AB  - The penetration of carumonam into the pleural exudate of rats was compared after
      intravenous administration of 30 mg kg(-1) of the drug as a bolus dose or by
      continuous infusion over 60 min. Both methods of administration ensured a good
      penetration of carumonam in pleural exudate, as measured by the areas under the
      concentration-time curves (AUC). The mean values of the ratio of AUC in exudate
      to AUC in serum (1.07 +/- 0.11 and 0.96 +/- 0.13 for bolus injection and
      continuous infusion, respectively) were not significantly different.
      Administration as a bolus dose resulted in significantly higher peak
      concentrations in pleural exudate as well as in shorter peak times, whereas
      continuous infusion produced carumonam levels above the MIC for consistently
      longer times. The pharmacokinetic parameters obtained by analysis of serum
      carumonam concentrations proved to be independent of the mode of administration.
      The foregoing results suggest that carumonam may constitute an effective
      therapeutic alternative to existing antibiotics for the treatment of pleurisy
      caused by susceptible organisms. No clear superiority of either method of
      administration could be established on the basis of pharmacokinetic data.

PMID- 18611547
TI  - Interactions between antimicrobial drugs and phagocytes: an overview.
AB  - The problems of microbial resistance and the increasing numbers of
      immunocompromised individuals have strengthened interest in new therapeutic
      strategies, including immunomodulation. Since phagocytes play both positive and
      deleterious roles in infectious diseases, they may be criticl targets in the
      study of drug-induced immunomodulation. Antimicrobial agents can modify phagocyte
      numbers] and functions in many ways. The main data and the implications of such
      interferences are reviewed in this paper.

PMID- 18611548
TI  - Ecological means of control of diarrhea.
AB  - In summary, altered intestinal ecology is very important in the pathogenesis of
      antibiotic-associated diarrhea and pseudomembranous colitis. Prevention of AAD
      has been demostrated with LactobacillusGG, Enterococcus SF68, and S. boulardii.
      While therapy with antibitics such as vancomycin or metranidazole is effective
      for PMC, relapse can occur and is difficult to treat. Antibiotics can be given,
      but another approach of restoring the normal colonic ecology may be more
      effective. Such therapy has included use of the nontoxigenic strains of C.
      difficile, rectal infusions of homologous feces or mixtures of bacteria, and oral
      administration of Lactobaccillus GG and the live yeast Saccharomyces boulardii.
      It is clear that many factors influence normal colonic homeostasis, including and
      individual's age, health, nutritions, medication, presence of gastrointentinal
      desease or surgery. The fetal flow is complex. Some factors related to C.
      difficile and disease production are known. For instance, only toxigenic strains
      cause disease, but rates of carrieage vary and not everyone with toxigenic
      strains of C. difficile will become ill. Studies of healthy volutenteers who took
      an oral cephalosporin antibiotic revealed that over 90% of them became colonized
      with C. difficile, and some excreted the organism for up to 26 days. Some
      volunteers had loose stools, but not was clinically ill[11]. Similary, neonates
      have a high rate of carriage of C. difficile and toxin (up to 60%), but usually
      are asymptomatic. Obviously, other factors besides presence of organism determine
      development of diseases. One such factor may the state of the immune system. In
      support of this are reports of recurrent C. difficile colitis in
      hypogammaglobulinemic children, and successful treatment of recurrent C.
      difficile colitis with intravenous gamma glubulin [51]. But recent studies of
      mucosal (secretory) IgA levels in C. difficile-associated diarrhea showed no
      clear-cut relaxationship of systemic or mucosol antibodies toxin A with the
      clinical course of C. Difficle infection [52] Other factors have not been
      explored, such as the influence of the diet. In addition, the intestinal flora
      may be allerted by bile acid production and/or pancreatics proteases.

PMID- 18611549
TI  - Current approach to the treatment of travellers' diarrhoea.

PMID- 18611550
TI  - Activity of cefixime against Helicobacter pylori.
AB  - The in vitro activities of cefixime, a new third-generation cephalosporin, and of
      18 other antimicrobial agents against 18 strains of Helicobacter pylori were
      determined. The strains of H. pylori were isolated from gastric biopsy specimens
      and tested for sensitivity to antibiotics by an agar dilution technique under
      microaerophilic conditions. Among cephalosporins, cefixime had the highest
      antibacterial activity, with a MIC for 90% of strains (MIC(90)) of 0.125 mg/l.
      Josamycin and erythromycin, aminoglycosides and the penicillin group tested were
      comparatively less active (MIC(90) < or = 0.5 mg/l). Ofloxacin (MIC(90) 0.5
      mg/l), ciprofloxacin (MIC(90) 0.125 mg/l) and the monobactam aztreonam (MIC(90) 4
      mg/l) were also active. All isolates were susceptible to rifampicin (MIC(90) 1
      mg/l) and resistent to cephalothin, cefsulodin and pefloxacin.

PMID- 18611551
TI  - Selective decontamination of the digestive tract for the prevention of infection.

PMID- 18611552
TI  - New treatment modalities for serious Gram-negative bacterial infections.

PMID- 18611553
TI  - The activity 'in vitro' of trospectomycin against high-level antibiotic-resistant
      enterococci.
AB  - Trospectomycin, a new aminocyclitol antibiotic, was uniformly active against 69
      isolates of enterococci with high-level resistance to steptomycin (54 isolates),
      gentamicin (27 isolates), ampicillin (19 isolates), ciprofloxacin (17 isolates),
      vancomycin (3 isolates), or teicoplanin (3 isolates). In time-killing studies,
      trospectomycin alone demonstrated no bactericidal activity. No synergistic
      interaction was demonstrated when trospectomycin was combined with ampicillin,
      vacomycin or ciprofloxacin.

PMID- 18611554
TI  - Lomefloxacin compared with trimethoprim for the treatment of women with cystitis.
AB  - A prospective, randomised, single-blind study compared the efficacy and safety of
      the long-acting difluoroquinolone, lomefloxacin, with trimethoprim for the
      treatment of women with cystitis. Seventy-five patients were treated with either
      lomefloxacin (400 mg once daily) or trimethoprim (300 mg once daily) for 5 days.
      Of the 75 patients enrolled, 47 were evaluable for efficacy. All patients treated
      with lomefloxacin and all but one treated with trimethoprim had a satisfactory
      clinical response. Twenty-three of 24 patients (96%) treated with lomefloxacin
      and 22 of 23 (96%) with trimethoprim had a satisfactory bacteriological response.
      All 75 patients were evaluated for safety. No serious side effects or toxicity
      were noted and no patients was withdrawn because of an adverse reaction. Both
      drugs proved highly effective and safe for the treatment of women with cystitis.

PMID- 18611555
TI  - Medical management of neurocycticercosis.

PMID- 18611556
TI  - Clinical trials of antibiotics: need for better investigators.

PMID- 18611557
TI  - Fluconazole (Diflucan): a review.
AB  - Fluconazole is a triazole antifungal agent available for oral or intravenous use
      in the treatment of a number of localized and disseminated mycoses. Animal models
      have shown in vivo activity against infections caused by Candida spp. and
      Crytococcus neoformans. Fluconazole is also active in animal infections caused by
      Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, and
      dermatophytes. Fluconazole acts by inhibiting synthesis of ergosterol, an
      essential sterol in fungal cell membranes. The drug is water-soluble, rapidly
      absorbed after oral dosing, and penetrates well into body fluids and tissues,
      including cerebrospinal fluid. It is excreted largely unchanged in urine and has
      an elimination half-life of approximately 30 h, allowing once-daily dosing.
      Extensive clinical trials document clinical efficacy in candidiasis - including
      oropharyngeal, esophageal, and disseminated forms - as well as in acute or
      suppressive therapy of cryptoccal meningitis. Other potential indications studied
      include prophylaxis of fungal infection in immunocompromised cancer patients,
      treatment of coccidioidal meningitis, and single-dose therapy of vaginal
      candidiasis. Fluconazole is generally well tolerated and infrequently associated
      with serious adverse effects or laboratory test abnormalities.

PMID- 18611558
TI  - Effect of fluconazole on the interactions between human neutrophils and Candida
      albicans.
AB  - The effects of fluconazole on the candidacidal activity of human neutrophils were
      investigated. Three clinical isolates of Candida albicans were studied in a
      colony count assay and the presence of fluconazole during incubation of yeasts
      with neutrophils had no effect on neutrophil candidacidal activity. These
      results, using a different assay and three additional isolates, confirm previous
      studies showing that fluconazole does not interfere with the ability of
      neutrophils to kill C. albicans.

PMID- 18611559
TI  - Preclinical studies with platelet-activating factor antagonists in models of
      septic shock.
AB  - Since the isolation and elucidation of the structure of platelet-activating
      factor (PAF) in the late 1970's, several preclinical studies have suggested that
      PAF is a key mediator of septic shock induced in animals by either endotoxin or
      by Gram-negative bacteria. A number of PAF antagonists have been sythesized that
      protect animals from the lethal effects of endotoxin. Some of these antagonists
      are in early stages of clinical development. The most advanced cadidate is BN
      52021, a ginkgolide, that is in Phase II/III clinical trials in patients with
      septic shock. Preliminary results with BN 52021 indicate that it is efficacious
      and significantly reduces mortality associated with Gram-negative sepsis. Pivotal
      trials with BN 52021 aer ongoing. The present review summarizes the biological
      effects of PAF and the effect of PAF antagonists in animal models of septic
      shock. The interrelationship of PAF and tumor necrosis factor (another key
      mediator of septic shock) is also discussed.

PMID- 18611560
TI  - Strategies for the treatment and prevention of cytomegalovirus infections.
AB  - Currently, only two drugs, i.e. ganciclovir, (DHPG, cytovene)_and foscarent (PFA,
      Foscavir), are licenced for the treatment of severe CMV infections. Both
      compounds may have serious side effects and can lead to the emergence of drug
      resistant virus strains. Recent pertain to the efficacy of prophylactic or pre
      emptive therapy with ganciclovir to prevent the development of CMV infections in
      transplant recipients. The search for safe and effective anti-CMV
      chemotherapeutics recently led to the development of some new promising anti-CMV
      compounds (HPMPC, cyclobutylguanine, benzimidazoles), of which HPMPC is currently
      undergoing clinical evaluation. Intravenous hyperimmune and normal gamma-globulin
      have been used prophylactically or therapeutically in the treatment of CMV
      disease. Some of the trials indicate that immunoglobulin prophylaxis might reduce
      the incidence or severity of CMV infections in transplant recipients. Some
      studies also claim prophylactic efficacy for acyclovir, whereas other conclude
      that acyclovir has little, if any, prophylactica activity in the prevention of
      CMV infections. The use of live attenuated or subunit CMV vaccines for the
      prevention of primary CMV infections in solid organ transplant recipients and
      pregnant women deserves further consideration. Another promising, recently
      reported, approach is the adoptive transfer of CMV-specific cytotoxic T-cells to
      the immuno suppressed host with the goal of conferring an adapted immune
      response.

PMID- 18611561
TI  - In vitro activities of two drug combinations of ceftazidime, cefotaxime,
      cefuroxime, ciprofloxacin, chloramphenicol, imipenem and temocillin against
      clinical isolates of Pseudomonas cepacia from patients with cystic fibrosis.
AB  - This study utilised the killing curve method to determine the in vitro effects of
      all possible two drug combinations of ceftazidine, cefotaxime, cefuroxime,
      ciprofloxacin, chloramphenicol, imipenem and temocillin against 10 strains of
      Pseudomonas cepacia isolated from the sputa of cystic fibrosis patients. The
      incidence of synergy was 21% and that of antagonism was 5.2%. Combinations
      associated with synergy for 30% of isolates were ceftazidime/cefotaxime,
      ceftazidime/cefuroxime, cefotaxime/ciprofloxacin, cefotaxime/chloramphenicol,
      ciprofloxacin/temocillin, and imipenem/ciprofloxacin. Combinations associated
      with synergy for 40% of isolates were ceftazidime/ciprofloxacin, cefotaximel
      temocillin, and imipenem/temocillin. The combination of ceftazidime/temocillin
      was associated with synergy against 70% of isolates. The present study therefore
      identifies several antibiotic combinations that may prove valuable, if confirmed
      in clinical studies, for treatment of P. cepacia infections.

PMID- 18611562
TI  - Antimicrobial resistance patterns in Korea.
AB  - Recent in-vitro test results showed that in Seoul (Korea) aerobic Gram-negative
      bacilli are often resistant to ampicillin and to the first-generation
      cephalosporins, but chloramphenicol-resistant Salmonella typhi are extremely
      rare. Almost all isolates of Moraxella (Branhamella) catarrhalis, 49% of
      Neisseria gonorrhoeae and 31% of Haemophilus influenzae were beta-lactamase
      producers. Seventhy-two percent of pneumococci were penicillin G resistant and
      62% of staphylococci were methicillin resistant. Among the Enterococcus faecium,
      59% were resistant to high-level gentamicin, but glycopeptide-resistant isolates
      were not found. Thirty-eight percent and 5% of Bacteroides fragilis were
      resistant to clindamycin and cefoxitin, respectively. In conclusion,
      antimicrobial-resistant bacteria are prevalent in Korea.

PMID- 18611563
TI  - Antibiotics may predispose to lactobacillemia in liver transplant patients.
AB  - Lactobacilli are ubiquitous inhabitants of the human oral cavity, vagina, and
      gastrointestinal tract, that are generally considered non-pathogenic. We
      retrospectively reviewed all positive blood cultures for Lactobacillus species
      (sp.) from liver transplant recipients at our institution. Eight cases of
      lactobacillus bacteremia were identified. Selective bowel decontamination with
      non-absorbable oral antibiotics was administered to all patients. Additionally,
      all patients received intravenous vancomycin; most isolates exhibited either in
      vitro or in vivo vancomycin resistance. The biliary anastomosis in each patient
      was a Roux-Y choledochojejunostomy. The underlying clinical conditions included
      perihepatic abscesses in two patients, biliary strictures with either hepatic
      abscesses or infected bile in four, and heaptic infarctions with necrosis and
      infection of the liver in two. The use of selective bowel deontamination,
      intravenous vancomycin and Roux-Y choledochojejunostomy in liver transplantation
      patients may predispose to lactobacillemia.

PMID- 18611564
TI  - The interaction of neutralized poliovirus with HeLa cells. II. Elution,
      penetration, uncoating.
AB  - The interaction of HeLa cells with adsorbed neutralized poliovirus was studied.
      In these experiments, 32P-labeled virus was allowed first to adsorb to cells and
      then to react with antibody, both reactions taking place at 2 degrees . The
      temperature was then raised to 37 degrees and the ensuing events were analyzed.
      The analyses were designed to measure the amounts of virus that were present as
      whole particles, as uncoated intact RNA, and uncoated degraded RNA. The analyses
      were made on the separated cell and fluid phases of each culture. In the control,
      in which virus had not been exposed to antibody, about 50% of the virus eluted
      from the cells into the fluid as a mixture of whole and degraded virus compared
      with about 25% for neutralized virus. In both cases almost all the eluted whole
      virus was not infectious and, except to a very small degree, was not reactivable
      by treatment with acid or sodium dodecyl sulfate, separately or together. More
      than 50% of the eluted material in the control was sedimentable at 100,000 g in
      contrast to about 10% if virus had been neutralized. An analysis of viral
      products, i.e., whole particles, intact RNA, degraded RNA found in association
      with cells or eluted from cells into the culture fluid, showed the following: (1)
      If combined with antibody, considerably less virus eluted as whole particles. (2)
      Antibody either reduced slightly or did not influence the proportion of RNA that
      was degraded and was contained either in the cells or in the fluid. (3) Whereas
      in the control appreciable amounts of intact RNA (10-15%) were found in the
      cells, little or none was found if virus was neutralized. (4) No intact RNA was
      found in the culture fluids in either case. Through the use of acid-treatment of
      virus-cell complexes for recovery of infectious virus, evidence was obtained
      indicating that neutralized virus penetrated cells at the same rate and to the
      same degree as unneutralized virus.

PMID- 18611565
TI  - Biological response modifiers and infectious diseases: actual and potential
      therapeutic agents.
AB  - Biological response modifiers (BRMs) are agents which can modify the immune
      response to cancer or invasion of the organism by infectious agents. An explosive
      appearance of new BRMs has resulted from the development of recombinant gene
      technology and the availability of monoclonal antibodies. Colony-stimulating
      factors first became available for the prevention of neutropenia but may also
      have a role in the treatment of infections. Interleukin-1 is being tested as a
      modular of hematopoiesis and may be useful as a helper factor for T- and B-cell
      function. Immunoglobulins are being used against viral and bacterial infections
      while interferons can prevent viral upper respiratory infections and suppress or
      irradicate some viral hepatitides. Other BRMs which show promise include chemical
      agents and traditional herbal medicines.

PMID- 18611566
TI  - Current infectious complications and their management in acute leukemia and bone
      marrow transplantation.

PMID- 18611567
TI  - Lyme borreliosis.

PMID- 18611568
TI  - beta-Lactum resistance in aerobic commensal faecal flora.
AB  - Faecal specimens from 100 healthy volunteers living in Edinburgh were examined
      for the presence of antibiotic-resistant bacteria. A high incidence of ampicillin
      resistance was found as 42% of specimens containing normally sensitive bacteria
      were resistant to the drug; however, only 12% of the specimens contained
      trimethoprim-resistant bacteria. There was no detectable resistance to the third
      generation cephalosporin, ceftazidime or the 4-quinolone, ciprofloxacin.
      Identification of the beta-lactamases produced by the ampicillin-resistant
      isolates demonstrated that the TEM-1 beta-lactamase predominated particularly in
      E. coli where it was identified in 86% of isolates. Thirty-three percent of the
      ampicillin-resistant isolates were able to transfer their resistance to E. coli
      K12 strain J62-2 and analysis of these transconjugants by iso-electric focusing
      revealed that the TEM-1 beta-lactamase was present in 100% of the
      transconjugants. Restriction endonuclease fingerprinting of the TEM-1 containing
      plasmids suggested the presence of an epidemic plasmid in the community.

PMID- 18611569
TI  - Comparison of Chinese and Western rifapentines and improvement of bioavailability
      by prior taking of various meals.
AB  - Bioavailability was measured by rifapentine (RPE) serum concentrations and by the
      urinary ratio between RPE and creatinine, in specimens obtained 4-50 h after 600
      mg RPE preceded by food. The bioavailabilities of RPEs manufactured in China and
      by a Western manufacturer were similar after a standard English breakfast, and
      serum concentrations were also similar to those obtained in an earlier Italian
      study following a complex meal. Although absorption of RPE was unsatisfactory
      after lipid-rich biscuits or shortbread, absorption after egges and toast was
      excellent and was nearly as good after a fast-food sandwich. The urinary measure
      of bioavailability at 26 h appeared as efficient as peak serum estimations at 6,
      8 and 26 h. Fast-food sandwiches are being taken before RPE in a current clinical
      trial of Chinese RPE in Hong Kong.

PMID- 18611570
TI  - Serum HIV-1 p24 levels and body weight measurements before and after 4 weeks of
      diethylcarbamazine treatment given to HIV-1 seropositive persons.

PMID- 18611571
TI  - Neonatal respiratory tract infections.
AB  - Neonatal respiratory tract infections, in particular pneumonia, can be life
      threatening. Lower respiratory tract infections may be acquired before, during,
      or after birth. Upper respiratory tract infections include otitis, sinusitis,
      rhinitis, laryngitis, tracheitis and bronchitis. Treatment of septicaemia and
      respiratory infections is based on the nature of the infection.

PMID- 18611572
TI  - Respiratory infections in the young child.
AB  - Infants and young children are prone to respiratory infections for at least
      immunological, physiological and social reasons. Their inherent immunity
      diminishes within months after birth. Immunological protection has to be
      developed naturally through infection or artificially by immunization. The
      alveoli continue to increase in number throughout infancy, but the pulmonary
      reserve remains very limited. Low lung recoil, floppy chest wall and weak
      respiratory muscles add to the risk of atelectasis of the growing lung. Social
      factors, e.g. day care, passive smoking and personal hygiene, are of even more
      pratical importance as they can be influential. In selecting appropriate
      treatment, it is not sufficient simply to prescribe an antimicrobial agent; these
      additional factors should also be taken into account. Treatment of respiratory
      infections in the young is sometimes more of an art than a science.

PMID- 18611573
TI  - Pneumonia in the elderly.
AB  - Pneumonia is the leading cause of death due to infectious disease in the elderly
      and the fourth most common cause of death overall. Streptococcus pneumoniae
      remains the main aetiological agent in community-acquired pneumonia. Aspiration
      pneumonia related to neuromuscular disease is also a frequent event. Pneumonia is
      the second most frequent hospital-acquired infection in long-term care
      facilities. For community-acquired pneumonia, initial therapy is most often
      empirical but invasive diagnostic tests may be required if signs of severity are
      present. Broad-spectrum coverage is usually required using a second- or third
      generation cephalosporin and only in the case of failure are invasive
      investigations necessary. Aspiration pneumonia may be treated with a combination
      of a beta-lactam and a beta-lactamase inhibitor. Initial therapy of nosocomial
      infections is based upon the susceptibility pattern of bacteria identified.

PMID- 18611574
TI  - Evaluating clinical outcomes of respiratory infection.
AB  - Evaluation of clinical outcomes of respiratory infection is essential to the
      audit of efficacy and safety of management practices. In order to examine the
      appropriateness of clinical outcome measurements in treated chronic respiratory
      infections, it is necessary to study a defined homogeneous population of treated
      patients. There is a fundamental difference between acute and chronic infection
      which governs the mode of antibiotic therapy. Understanding of the pathogenesis
      of chronic respiratory infection also allows more logical use of antimicrobial
      agents and more logical assessment of their efficacy, taking into account the
      tissue-damaging inflammation which might be controlled by anti-inflammatory
      combined with antibiotic therapy. This contrasts with acute infection in the
      immunocompetent host, in whom virulent bacteria overwhelm the host's immune
      defences temporarily so that a brief period of antibiotic therapy may reduce
      bacterial counts and host immune defences achieve killing of bacteria.

PMID- 18611575
TI  - beta-Lactam antibiotics in respiratory tract infections.
AB  - beta-Lactam antibiotics have played a major role in the treatment of respiratory
      infections for many years. The use of the three main groups of beta-lactam
      antibiotics-penicillins, cephalosporins and non-classical beta-lactams-in
      respiratory infections is reviewed. Their development and efficacy have more or
      less kept pace with the changes in microbial resistance, emergence of new
      pathogens and changes in medical practice. Consequently, beta-lactam agents
      continue to make a valuable contribution to therapy of respiratory tract
      infections.

PMID- 18611576
TI  - Interpretation of pharmacologic data in respiratory tract infections.
AB  - Few serum pharmacokinetic parameters of antibiotics are predictors of tissue
      distribution and, for instance, more useful are studies of tissue concentrations
      in the respiratory tree. Significant antibiotic concentrations can be obtained at
      various sites of potential infection: lung parenchyma; alveolar macrophages; and
      bronchial mucosa and secretions. New models using broncho-alveolar lavage allow
      studies of antibiotic concentrations in epithelial lining fluid that are good
      predictors of antibiotic activity in lung infections. In studies in human
      respiratory tissues for superinfected bronchitis, concentrations of macrolides,
      quinolones or beta-lactans in bronchial secretions, or mucosa, correlated with
      satisfactory clinical response, and eradication of pathogens. Pulmonary kinetics
      of aminoglycosides or beta-lactams have been studied using a canine model. Also
      in murine models of pneumonia, pharmacokinetic parameters have been determined
      for quinolones and newer macrolides.

PMID- 18611577
TI  - Tetracyclines-extending the atypical spectrum.
AB  - The main features and the present position of tetracyclines are reviewed. The
      mechanism of their action, bacterial resistance and the most recent findings are
      reported. Their decreased use is due to the availability of new, active, better
      tolerated antibiotics. However, tetracyclines still have a place in the treatment
      of chlamydial and rickettsial infections, brucellosis and Lyme disease. In
      respiratory infections, they can be employed when necessary in infections caused
      by Chlamydia psittaci, C. pneumoniae, Mycoplasma pneumoniae, and also by
      Streptococcus pneumoniae and Haemophilus influenzae, whose rates of resistance
      now seem lower than in the past when tetracyclines were more largely prescribed.

PMID- 18611578
TI  - Fluoroquinolones in bronchopulmonary infections.
AB  - In recent years, Streptococcus pneumoniae and Haemophilus influenzae, two of the
      most common pathogens causing bronchopulmonary infections, have developed
      resistance towards beta-lactam antibiotics in many areas of the globe. In some
      countries, resistance rates are so high that treatment with penicillin can not be
      recommended as the therapy of choice. Unfortunately, many S. pneumoniae strains
      resistant to penicillins are also resistant to co-trimoxazole and erythromycin,
      and even to the novel macrolides. Present fluoroquinolones may have to be used in
      such resistant cases. The fluoroquinolones possess a superior activity against H.
      influenzae and other pathogens causing bronchitis and pneumonia. Fluoroquinolones
      have a favourable pharmacokinetic profile including penetration into sputum,
      bronchial fluid, alveolar lining fluid and alveolar macrophages, and therapeutic
      concentrations and ratios are superior to those of the beta-lactams.
      Fluoroquinolones have been shown to produce better results than the comparative
      agents in bronchitis and, in cystic fibrosis, they achieve a definite clinical
      amelioration in paediatric patients without substantial additional toxicity.
      Their use in legionnaires' disease has not been confirmed and their place in the
      treatment of community-acquired pneimonias - particularly those caused by
      Mycoplasma pneumoniae and Chlamydia trachomatis and the TWAR agent - deserves
      further investigation.

PMID- 18611579
TI  - The use of macrolides in respiratory tract infections.
AB  - Macrolides have enjoyed continued use for over 40 years, being increasingly used
      for the treatment of respiratory tract infections. Newer macrolides have been
      introduced that show improved absorption after oral administration, better
      gastrointestinal tolerance, and delivery of increased amounts of drug to the
      infection site. Macrolides are commonly used in community-acquired pneumonia, as
      well as in atypical pneumonia and legionellosis. The newer macrolides, in
      comparative studies, have been shown to be as affective as the conventional
      therapies for treating acute otitis media, acute sinusitis and acute pharyngitis,
      with a low incidence of side-effects. However, dosing can be simplified because
      of their unique pharmacokinetic properties. Limitations in the use of macrolides
      for respiratory infections include rather marginal activity in the most severe
      cases of Haemophilus influenzae infections, lack of activity against Klebsiella
      and other coliforms, which precludes their use as single agents in the therapy of
      pneumonia in patients with significant underlying disease or in the elderly, and
      development of resistance in streptococci and staphylococci.

PMID- 18611580
TI  - Evaluation of antibiotics for treatment of respiratory infections - general
      discussion.

PMID- 18611581
TI  - Community-acquired respiratory infection: keeping patients at home.
AB  - This overview focuses on two types of lower respiratory infections: acute
      bacterial exacerbations of chronic bronchitis and community-acquired pneumonia.
      Each of these types of respiratory infection is responsible for considerable
      morbidity, and in some instances mortality, in adults every year. Not all adult
      cases, however, require hospitilization. Specifically, prompt initiation of
      appropriate antimicrobial therapy is of primary importance in minimizing the
      deleterious effects of acute bacterial exacerbations of chronic bronchitis. The
      majority of patients can be treated effectively as out-patients. Similarly, most
      patients with community-acquired pneumonia can be cared for at home. The need for
      hospitalization must be determined individually and is based upon the severity of
      the patient's illness as well as the presence of associated underlying disease.

PMID- 18611582
TI  - Atypical pneumonias: therapeutic possibilities.
AB  - The atypical pneumonia syndrome is characterized by systemic complaints rather
      than respiratory symptoms. The causative pathogens include Mycoplasma, Chlamydia,
      Legionella and respiratory viruses (influenza, adenovirus, respiratory syncytial
      virus). The reported incidence of disease caused by these pathogens in community
      acquired pneumonias varies from study to study. As most of these pathogens are
      intracellular, the antibiotics used in the treatment of atypical pneumonia are
      those able to penetrate into cells. Empirical antimicrobial therapy consists of
      macrolides (erythromycin or some of the newer agents such as roxithromycin,
      azithromycin or clarithromycin) or tetracyclines (e.g. doxycycline). In cases of
      severe legionellosis and in immunocompromised and critically-ill patients, the
      macrolides are sometimes given in combination with rifampicin. Promising
      alternatives are some of the newer fluoroquinolones (e.g. ofloxacin, pefloxacin)
      in the treatment of legionellosis.

PMID- 18611583
TI  - Therapeutic possibilities for diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis can be thought of as one of the biofilm diseases of
      which cystic fibrosis is another example. The patient often has persistent
      infection with Pseudomonas aeruginosa and, in 1982, the survival rate to 5 years
      in these patients was only 37%. Recently, the prognosis of these patients has
      remarkably improved by using long-term treatment with 14-membered macrolides.
      However, the reason for the effect of macrolides in these patients is still
      obscure. To try to understand this pneumonia, some experiments were performed to
      assess the effect of macrolides on P. aeruginosa biofilm. An in vitro biofilm of
      P. aeruginosa was prepared on Teflon after 6 days' incubation and the effects of
      antibiotics on the biofilm were assessed. Floating, but not biofilm bacteria were
      killed by meropenem, ciprofloxacin, tosufloxacin and cefoperaxone. Ciprofloxacin
      with either azithromycin or clarithromycin killed bacteria within the biofilm,
      whereas ciprofloxacin with clindamycin, josamycin or other 16-membered macrolides
      was ineffective. Clarithromycin destroyed the biofilm, releasing the bacteria
      into the medium. The ability of P. aeruginosa to adhere to murine tracheal cells
      was also reduced by clarithromycin. These kinds of macrolides may have some sort
      of permeability effect on the biofilm surface and this may bear some relation to
      the good clinical performance of macrolides in diffuse panbronchiolitis.

PMID- 18611584
TI  - Nosocomial pneumonia: pathogenesis, diagnosis, current therapy and prophylactic
      approach.
AB  - Pneumonia is the second most common hospital-acquired infection, occurring more
      frequently in mechanically-ventilated patients, and is the leading cause of death
      from nosocomial infections. Pathogenesis is linked with oropharyngeal flora
      aspiration when colonized with Gram-negative organisms either directly from the
      environment or retrogradely from the stomach whenever the pH is > 4. The main
      pathogens implicated are Enterobacteriaceae and Pseudomonas aeruginosa. Routine
      sputum cultures are unreliable because of contamination with oropharyngeal flora;
      however, a bronchoscopic protected specimen brush and bronchoalveolar lavage
      techniques may overcome this problem. A combination of broad-spectrum antibiotics
      and monotherapy with newer antimicrobial agents appear to be equally effective in
      treatment of nosocomial infections. The efficacy of prophylaxis after selective
      gut decontamination in intensive care unit patients, however, has not yet been
      established.

PMID- 18611585
TI  - Respiratory infections in the immunocompromised patient.
AB  - Damage to local and systemic defences of the lungs makes the immunocompromised
      host vulnerable to inhaled microorganisms. The type of underlying disease and its
      associated immunodeficiency allow a high degree of accurate pathogen prediction.
      Neutropenia is associated with Gram-negative bacilli pneumonia. Prolonged
      neutropenia increases the risk of aspergillosis and mucormycosis. Cellular
      immunodeficiency is associated with Pneumocystis carinii, Legionella spp. and
      intracellular parasites including Mycobacteria spp., Nocardia spp. Rhodococcus
      equi, cytomegalovirus, Strongyloides stercoralis, Histoplasma capsulatum and
      Coccidioides immitis. Humoral immunodeficiency predisposes to infection with
      Streptococcus pneumoniae and Haemophilus influenzae. Chest computerized
      tomography scan and bronchoalveolar lavage are essential procedures for
      diagnosis. Successful therapy depends on the type of pathogen, status of host
      defence sand early adequate choice of antibiotics. Enhancement of host defences
      with growth factors, cytokines and interferons can ameliorate the outcome.

PMID- 18611586
TI  - Viral infections of the respiratory tract: prevention and treatment.
AB  - The rapid discovery of specific viral agents as the cause of many acute
      respiratory diseases was accompanied by considerable optimism that vaccines or
      other control measures could be developed quickly. Subsequent experience has
      demonstrated that effective control of these important public health problems has
      been an elusive goal. However, recent exciting developments in our understanding
      of the molecular biology and immunology of these viruses may provide the basis
      for more effective strategies in the future.

PMID- 18611587
TI  - Cefuroxime axetil.
AB  - Cefuroxime is the first commercially-available second-generation cephalosporine
      to be widely used in therapy; it is a semi-synthetic cephalosporin obtained from
      the 7-cephalosporanic acid nucleus of cephalosporin C. Cefuroxime axetil is the
      acetoxyethyl ester of cefuroxime. The majority of micro-organisms associated with
      respiratory infections are highly sensitive to cefuroxime. These include
      Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes and the
      other streptococci (excluding group D streptococci), and Moraxella catarrhalis.
      Bacteria sensitive to cefuroxime include the enterobacteria (Escherichia coli,
      Klebsiella pneumoniae, Proteus mirabilis, and Salmonella and Shigella and
      Straphylococcus aureus (methicillin-sensitive strains). The pharmacokinetic
      studies show that the maximum plasma concentration of cefuroxime after oral
      administration of 250 mg and 500 mg of cefuroxime axetil after a meal are
      respectively 4.6 and 7.9 mg/l. The absolute bioavailability of tablets is 68%
      (extremes 63-73%) after oral administration of 500 mg cefuroxime axetil. The
      protein binding is 33+/-5.7%. Tissue diffusion was studied in the interstitial
      fluid, the bronchial mucosa, the tonsils, and the bronchial secretions.
      Cefuroxime axetil is available as capsule-shaped tablets containing 125, 250 or
      500 mg. An oral suspension dosage form for paediatric purposes is also available
      as granules in multidose bottles and sachets. Constitution gives a suspension
      containing 125 mg or 250 mg cefuroxime (as cefuroxime axetil). Cefuroxime axetil
      is indicated for the treatment of infections caused by susceptible bacteria.
      Indications include: lower respiratory tract infections (e.g., acute and chronic
      bronchitis and pneumonia); upper respiratory tract infections (e.g., ear, nose
      and throat infections such as otitis media, sinusitis tonsillitis and
      pharyngitis); genito-urinary tract infections (e.g., pyelonephritis, cystitis and
      urethritis, gonorrhoea, acute uncomplicated gonococcal urethritis and
      cervicitis); and skin and soft tissue infections (e.g., furunculosis, pyoderma
      and impetigo). For most infections, a dose of 250 mg twice daily is appropriate.
      In some urinary tract infections, 125 mg twice daily has been shown to be
      effective. If pneumonia is suspected or in more severe lower respiratory tract
      infection, doses of 500 mg bd should be used. Uncomplicated gonorrhoea has been
      shown to respond to a single 1-g dose of cefuroxime axetil. Adverse reactions to
      cefuroxime have generally been mild and transient in nature (gastrointestinal
      disturbances, including diarrhoea, nausea and vomiting).

PMID- 18611588
TI  - Cefpodoxime proxetil: a comprehensive review.
AB  - Cefpodoxime proxetil, a relatively new broad-spectrum third-generaation
      cephalosporin, has very good in vitro activity against Enterobacteriaceae,
      Hemophilus spp. and Moraxella spp., including beta-lactamase producers and many
      strains resistant to other oral agents. It also has activity against Gram
      positive bacteria, especially against streptococci. Cefpodoxime has no activity
      against enterococci. It is well tolerated and is one of the first third
      generation cephalosporins to be available in oral form. While the compound has
      been used most widely in the treatment of respiratory and urinary tract
      infections, its utility has also been demonstrated in the treatment of skin
      structure infections, acute otitis media, pharyngitis, tonsillitis, and sexually
      transmitted diseases.

PMID- 18611589
TI  - Pneumococcal resistance to the third-generation cephalosporins: clinical,
      laboratory and molecular aspects.
AB  - Widespread use of third-generation cephalosporins appears to have selected
      cephalosporin-resistant pneumococci associated with the failure of these agents
      in the management of meningitis. Breakpoints of 0.5 mg/l for intermediate and 2
      mg/l for full resistance are proposed for the treatment of pneumococcal
      meningitis. As no disc tests reliably identify these breakpoints, MIC or E test
      confirmation of third-generation cephalosporin resistance is recommended for all
      strains found resistant to a 1 mug oxacillin disk. Resistant strains can be
      selected in a single transformation event, with PBP 2X gene rearrangements
      conferring low level resistance and PBP 1A gene rearrangements conferring full
      resistance.

PMID- 18611590
TI  - Development of amikacin resistance in bacterial isolates in Slovakia (1990-1992).
AB  - In-vitro susceptibility of 7301 clinical isolates of Gram-negative bacilli,
      originating from hospitals at and around Bratislava, to amikacin was evaluated
      during the years 1990-1992. In 1990 amikacin resistance represented 4.1%, in 1991
      it increased to 7.3% and in 1992 a slight decline to 6.4% was observed. In
      Slovakia during the last decade amikacin usage increased by 300%. The
      predominating mechanism of resistance was production of modifying enzymes, mainly
      in Enterobacteriaceae. The unique enzyme inactivating amikacin was AAC(6')-I.
      This enzyme was found in all isolates in combination either with APH(2''),
      characteristics up to now only for staphylococci, or with AAC(3) enzyme.

PMID- 18611591
TI  - Current issues on the prophylaxis and the management of fungal infections in
      leukemic patients.
AB  - During the last few years, recent developments of the antifungal armamentarium
      have led to large studies on chemoprophylaxis as well as on new therapeutic
      regimen using new antifungal agents such as triazoles but also new modalities to
      administer amphotericin B. This progress, combined with increased awareness of
      clinicians about the high morbidity and mortality related to invasive fungal
      infection, suggests that there will be significant improvement of the prognosis
      for immunocompromised patients at risk of invasive fungal infections.

PMID- 18611592
TI  - Introduction.

PMID- 18611593
TI  - The management of urinary infections: what have we learned in the past decade?
AB  - User-friendly, cost-effective practices to manage urinary infection should become
      routine. The vast majority of inflections are relatively easy to treat and many
      of these can be prevented with appropriate interventions. Additional research is
      urgently needed to compare various clinical strategies and determine which is
      most acceptable to patients at a reasonable cost with satisfactory health
      outcomes.

PMID- 18611594
TI  - The mucosal cytokine response to urinary tract infections.
AB  - This review focussed on the cytokine responses to urinary tract infections.
      Colonization of the human urinary tract with E. coli activates the intermittant
      secretion of IL-6 and IL-8 into urine. In contrast, local bacterial challenge did
      not give rise to detectable serum IL-6 or IL-8 levels. IL-6 is detected in the
      urine at the time of diagnosis in most patients with natural urinary tract
      infections; however, IL-6 was only detected in the serum of symptomatic patients.
      These observations suggested that the cytokine response during UTI can have local
      and systemic components. Epithelial cells have been examined as a likely source
      of the local cytokines produced in response to UTI. The profile of cytokines
      produced by uroepithelial cells in response to E. coli is similar to that
      secreted during UTI (IL-6 and IL-8, but no IL-1 or TNF). Adhering bacteria and
      isolated P fimbriae stimulate higher levels of IL-6 production in cells that
      express the globoseries of glycolipids such as kidney epithelial cells.
      Uroepithelial cells also respond to stimulation by cytokines; IL-1alpha and
      TNFalpha induce the secretion of IL-6 and IL-8 and the upregulation of mRNAs for
      IL-1alpha, IL-1beta, IL-6 and IL-8. This cytokine profile is similar to that
      detected after bacterial stimulation; however, the magnitude and kinetics of the
      epithelial cell cytokine responses differed between the stimulants. Interleukin-4
      induced epithelial cell IL-6 and IL-8 production; gamma-interferon only induced
      IL-6 production. This suggests that epithelial cells produce primary and
      secondary cytokine responses, and can function in mucosal cytokine networks with
      a variety of cells. Cytokines are mediators of immune functions and inflammation
      and it is likely that the local cytokine production influences both the induction
      of symptoms as well as the eventual outcome of the infection. Examination of
      local cytokine levels during UTI may prove to be a useful diagnostic tool;
      however, this possibility requires further evaluation.

PMID- 18611595
TI  - Management of uncomplicated urinary tract infections.
AB  - The majority of urinary tract infections (UTIs) present as bacterial cystitis in
      women in the sexually active age group. The commonest pathogen is Escherichia
      coli and the majority of the remainder are due to Staphylococcus saprophyticus.
      Many women are prone to recurrent UTIs and these are invariably due to a
      reinfection with a different organism. After the diagnosis has been made a
      curative course of treatment should be given, but the approach can be modified if
      the infection is uncomplicated (normal urinary tract and normal renal function)
      as opposed to complicated. It is widely believed that traditional dosage
      regiments for uncomplicated UTIs are extravagant. There is now considerable
      enthusiasm for the use of either single-dose therapy or for a course of treatment
      not exceeding 3 days for uncomplicated cystitis. Failure of single-dose therapy
      is a simple guide to the need for further urinary tract investigation or more
      intensive therapy. Patients with uncomplicated acute pyelonephritis should be
      treated for at least 5 days and this may need to be given parenterally if the
      patient is vomiting. If a woman is having recurrent UTIs it may be necessary to
      consider long-term, low-dose prophylaxis. The most effective drugs used in this
      way include nitrofurantoin 50 mg, trimethoprim 100 mg and norflaxacin 200 mg
      given at night. More recent studies have shown that a dose given alternate
      nights, 3 nights a week of just after intercourse is just as affective.

PMID- 18611596
TI  - Host defense mechanism in the pathogenesis of UTI and UTI in immunocompromised
      patients.
AB  - Defects in the immune system determine the clinical manifestations and severity
      of urinary tract infections (UTI) and the rates of complication but they only
      have an indirect role in influencing susceptibility to infection. The rates of
      UTI in diabetics, renal transplant, recipients, neutropenic patients, and
      patients with AIDS are primarily determined by the degree and duration of urinary
      tract manipulation and the higher perineal prevalence of potential pathogens that
      result from frequent hospitalization and antimicrobial use. Prompt recognition
      and treatment of established infections is critical to prevent life-threatening
      complications (e.g. bacteremia, emphysematous pyelonephritis) but routine
      screening for asymptomatic bacteriuria is indicated only in kidney recipients
      less that 3 months post-transplantation.

PMID- 18611597
TI  - Consequences of asymptomatic bacteriuria in the elderly.
AB  - Asymptotic bacteriuria increases with advancing age for the ambulatory
      population. Men and women who are resident in long-term care facilities have an
      exceptionally high prevalence of bacteriuria. Despite this high prevalence and a
      high incidence of bacteriuria, urinary infection contributes little to morbidity
      and mortality in the elderly. While urinary infection is the most common source
      of bacteremic infection in the elderly, episodes of symptomatic urinary are
      infrequent relative to respiratory, gut, and skin infections. Substantial long
      term complications of asymptomatic bacteriuria in the elderly have not been
      identified and there is no convincing evidence that asymptotic bacteriuria is
      associated with impaired survival. Further studies of the impact of asymptomatic
      bacteriuria in elderly populations to better define the association with
      symptomatic infection are needed.

PMID- 18611598
TI  - Urinary tract infection in patients with diabetes mellitus.
AB  - Urinary tract infections (UTI) are very often encountered in patients with
      diabetes mellitus. They may present themselves as asymptomatic bacteriuria, but
      may also lead to more serious infections. In most cases the kidney is involved,
      although signs and symptoms of renal infection may not be present. Asymptomatic
      bacteriuria is more prevalent in women, but no men, with diabetes mellitus
      compared to controls. Studies yield conflicting results, probably due to
      selection bias, about associated risk factors. The pathogens cultured are those
      seen in all complicated urinary tract infections. The suggested mechanisms of an
      increased susceptibility to UTI are (a) decreased antibacterial activity due to
      the 'sweet urine', (b) defects in neutrophil function and (c) increased adherence
      to uroephithelial cells. The latter is the most likely. UTI in diabetics should
      be treated as complicated UTI with agents reaching high tissue levels for 10-14
      days.

PMID- 18611599
TI  - Catherer-associated urinary tract infections: epidemiological, preventive and
      therapeutic considerations.
AB  - Urinary tract infections (UTI) continue to be the single most common type of
      nosocomial infection, the majority of which are catherer-associated (UTI(c)).
      REstricted use and timely removal of indwelling chatheters, strict adherence to
      the principles of closed sterile drainage and use of antimicrobials, either
      intentional or concurrent, are the only factors considered to have an appreciable
      and consistent impact on the prevention or postponement of UTI(c). The
      epidemiology, pathogenesis, prevention and treatment of UTI(c) are discussed in
      more detail. Targeted antibiotic prophylaxis in carefully selected well
      identifiable groups of cathetirized patients and use of catheters that better
      resist biofilm formation and/or have bactericidal properties should be the
      subject of future prospective studies.

PMID- 18611600
TI  - Complicated urinary tract infections.
AB  - No standard definition exists for the term, complicated urinary tract infection.
      The term is usually used to convey an infection that occurs in a host with
      altered defenses or in a patient with a structural or functional abnormality
      impeding urine flow. Therapy of complicated infections represents a greater
      challenge than treatment of uncomplicated urinary tract infections. Drug
      treatment of complicated urinary tract infections often must be complemented with
      radiological/surgical intervention. Trimethoprim-sulfamethoxazole and the newer
      quinolone compounds are currently the preferred agents for the treatment of
      complicated urinary tract infections. There exists a dearth of well designed
      published studies to serve as a resource for treatment guidelines.

PMID- 18611601
TI  - Useful agents in the management of urinary tract infections.
AB  - Urinary tract infections (UTIs) encompass a large variety of clinical conditions
      ranging from asymptomatic bacteriuria in healthy individuals to life-threatening
      bacteraemic infections. The choice of antibiotic therapy must be based on
      identification of the type of UTI to be treated, possible contraindicating
      factors with the individual patient and, above all, knowledge of the antibiotic
      resistance pattern in the geographical area where the patient acquired the
      bacteriuria. In many countries trimethoprim-sulphonamide combinations,
      trimethoprim plain or nitrofurantoin are still useful drugs. Generally, the
      clinical efficacy of oral beta-lactams such as amoxicillin, ampicillin and
      cephalosporins seems to be less good than those of fluoroquinolones and the above
      mentioned antibiotics. However, too frequent use of quinolones may lead to
      increased frequencies of resistance to those antibiotics in common species such
      as Escherichia coli. It is therefore recommended not to used fluoroquinolones in
      patients with sporadic uncomplicated cystitis, i.e., the most common type of UTI,
      but to reserve the modern quinolones for patients with pyelonephritis,
      complicated UTI or recurrent UTI.

PMID- 18611602
TI  - Management of candiduria.
AB  - Candiduria, due to Candida albicans, Candida glabrata and other organisms, has
      increased in frequency due the use of broad-spectrum antibacterials,
      immunosuppressive agents and other factors. The optimal management of candiduria
      is unknown due to an unclear definition of fungal urinary tract infection and the
      lack of well-designed clinical trials. Removal of urinary catheters, ruling out
      obstruction/stones and documenting presence of post-void residuals are useful in
      the management of candiduria. Amphotericin B bladder irrigants and oral
      fluconazole may be used in certain patients who are high risk or with persistence
      of candiduria after removal of the urinary catheter.

PMID- 18611603
TI  - Worldwide resistance against antibiotics.

PMID- 18611604
TI  - Resistance to antimicrobial agents of common bacteria isolated from Taiwan.
AB  - Antimicrobial susceptibility of 11 commonly seen and/or important pathogenic
      bacteria isolated from the National Taiwan University Hospital in 1981 and 1992
      was analysed. Oxacillin-resistance was most remarkable in Staphylococcus aureus.
      Its prevalence increased rapidly from 6.7% in 1981 to 49.7% in 1992. A high
      proportion of oxacillin-resistance was also found in coagulase-negative
      staphylococci, both in 1981 and in 1992. For Streptococcus pneumoniae, no
      penicillin-resistant nor erythromycin-resistant strain was found in 1981, but by
      1992, 5.8% of the isolates were penicillin-resistant 42.3% erythromycin
      resistant. Gentamicin-resistance was the most common problem in enterococci, with
      70.6% resistance in 1992. As to Gram-negative bacteria, Enterobacter spp.
      demonstrated a high proportion of resistance to various antimicrobial agents:
      more than 72% susceptibility was found only for amikacin. Pseudomonas aeruginosa
      was also a highly resistant bacterium, with only 50 to 90% of susceptibility to
      various antipseudomonal agents. In Haemophilus influenzae, both ampicillin
      resistance and chloramphenicol-resistance were remarkable, with 52.2% and 32.9%
      resistance, respectively, in 1992.

PMID- 18611605
TI  - Activity of eight fluoroquinolones against methicillin-resistant Staphylococcus
      aureus isolated from cutaneous infections.
AB  - The in vitro susceptibility of methicillin-resistant Staphylococcus aureus to
      eight fluoroquinolones, norfloxacin, ofloxacin, enoxacin, ciprofloxacin,
      lomefloxacin, sparfloxacin and nadifloxacin, was evaluated. Methicillin-resistant
      S. aureus strains were isolated from 64 cutaneous infections from 1991 to 1993.
      Nadifloxacin exhibited the lowest MIC among all of the fluoroquinolones. In
      addition, there was no resistance to nadifloxacin. The MIC(50) of these drugs has
      been increasing in the past 3 years.

PMID- 18611606
TI  - The concentration of sparfloxacin in lung tissues after single and multiple oral
      doses.
AB  - The levels of sparfloxacin were measured in serum, alveolar macrophages,
      epithelial lining fluid (ELF) and bronchial mucosa after single and multiple oral
      doses. Measurement was performed using a microbiological assay technique. There
      were 21 subjects in the single dose and 10 subjects in the multiple dose groups.
      Following a single 400 mg dose of sparfloxacin the mean levels after 11-15 h were
      1.2 mg/l in serum, 61.3 mg/l in macrophages, 9.8 mg/l in ELF and 2.6 mg/kg in
      mucosa. After multiple dosing of 400 mg on day 1 followed by 200 mg daily for the
      next 2 days the mean levels were 1.2 mg/l in serum, 53.7 mg/l in macrophages,
      15.0 mg/l in ELF and 4.4 mg/kg in mucosa. These data predict good clinical
      efficacy in respiratory tract infections.

PMID- 18611607
TI  - Treatment and developmental therapeutics of Mycobacterium tuberculosis
      infections.
AB  - Tuberculosis still remains a serious health problem in many regions of the world,
      especially in developing nations. With the spread of AIDS and the increase in the
      number of immunocompromised patients, the problem of tuberculosis has been
      greatly exacerbated because of the susceptibility of such patients to
      mycobacteria. Currently, chemotherapy using multiple drug regimens with
      isoniazid, rifampin, streptomycin, pyrazinamide, and ethambutol is the
      recommended treatment for tuberculosis. The presence of drug resistance is still
      a major concern and new generations of more effective antimycobacterial agents
      (antibiotics, fluoroquinolone derivatives) are the subject of active
      investigation. The search for novel strategies to cure tuberculosis led to
      studies exploring the role of cytokines in host defenses and the application of
      adoptive immunotherapy. New and improved methodology for in vitro and in vivo
      screening of antimycobacterial activity has also been reported.

PMID- 18611608
TI  - In vitro and in vivo activities of clarithromycin against the Mycobacterium avium
      complex.
AB  - Clarithromycin (CAM) was assessed for in vitro antimicrobial activity against
      various mycobacterial species. Except for Mycobacterium tuberculosis, CAM
      displayed MICs for test mycobacteria comparable to those of sparfloxacin (SPFX)
      but lower than those of rifampicin (RMP) and ofloxacin (OFLX). CAM at 0.25 mug/ml
      (1 MIC) exhibited bactericidal action against M. intracellulare growing in 7H9
      medium and at 1 or 10 mug/ml (4 and 40 MIC, respectively) CAM displayed
      antimicrobial activity against the organism phagocytosed in murine macrophages,
      while RMP failed to manifest such an effect. When CAM was given s.c. or by gavage
      to mice infected i.v. with M. intracellulare at doses of 0.2 to 2 mg/mouse once
      daily, six times per week, it exhibited significant therapeutic efficacy in terms
      of decreased incidence of gross lung lesions and reduced bacterial loads in the
      lungs and spleen.

PMID- 18611609
TI  - Macrolide transport in Escherichia coli strains having normal and altered OmpC
      and/or OmpF porins.
AB  - [(14)C]Erythromycin and [(14)C]azithromycin uptake rates were studied in
      Escherichia coli strains containing normal OmpC and OmpF porins (strain MRC 106)
      and altered OmpC porins due to small insertions (strains RAM121 and OC1555) or
      deletions (strain RAM122) in the ompC alleles and altered OmpF porins due to
      small ompF deletions (strains OC1555 and PLB3255). Strains RAM121 and RAM122 also
      lacked OmpF porins in their outer membrane. The porin mutants demonstrated a 2-
      to 1224-fold increase in macrolide transport and a concurrent 3- to 530-fold
      decrease in MIC when compared to the parent strain, MCR106. Both strains OC1555
      and PLB3255 had enhanced permeability to 1-N-phenylnaphthylamine indicating
      increased permeability of the outer membrane to hydrophobic molecules. The
      macrolides, at 2 to 1000 times MIC, failed to displace the cationic probe
      polymyxin; therefore, drug entry by a self-promoted mechanism was not indicated.
      Since >95% of macrolide is protonated and thus hydrophilic (logP(i)=-0.89) at
      neutral pH, the bulk of drug entry may be via the porin channels.

PMID- 18611610
TI  - Antibiotics enhance binding of lipid A-specific murine monoclonal antibody E5 to
      Gram-negative bacteria.
AB  - Cross-protection by anti-lipid A antibodies may be mediated by contribution to
      host defence mechanisms such as enhancement of bactericidal activity and
      phagocytosis. The lipid A-specific murine monoclonal antibody (mAb) E5 was
      evaluated in vitro for its ability to enhance antibacterial effects in concert
      with antibiotics in order to investigate underlying mechanisms for the proposed
      in vivo efficacy. The effect of antibiotic exposure of several E. coli strains on
      binding by mAb E5 was examined in solid phase enzyme-linked immunoassay (ELISA)
      and in complement activation and phagocytosis assays. MAb E5 binds scarcely to
      live E. coli, both encapsulated and unencapsulated, but exposure to subinhibitory
      concentrations of aztreonam and ceftriaxone led to enhanced binding of mAb E5
      compared to mock treated strains. Enhanced binding of mAb E5 to aztreonam-treated
      E. coli O111:B4 or O7K1 resulted in a modest increase in complement consumption
      but complement-mediated phagocytosis by human polymorphonuclear leukocytes (PMN)
      of these complexes was not affected. It was concluded that exposure of E. coli to
      antibiotics induced specific alterations in the bacteria, resulting in
      accessbility of epitopes recognized by mAb E5. Enhanced binding was found to
      support complement-mediated host defense mechanisms and might contribute to
      better protection in a joint action of antibiotics and antibodies.

PMID- 18611611
TI  - Pefloxacin single-dose in the treatment of acute uncomplicated lower urinary
      tract infections in women: a meta-analysis of seven clinical trials.
AB  - The objective of the meta-analysis was to assess the efficacy and safety of a
      single oral dose of 800 mg pefloxacin in the treatment of acute uncomplicated
      lower urinary tract infections in women. A total of 1578 women were enrolled in
      five controlled (four double-blind and one open) and two non-comparative
      multicentre clinical trials. The comparative treatment regimen in the five
      controlled trials was trimethoprim-sulfamethoxazole in four studies, and
      norfloxacin in one study. Trimethoprim-sulfamethoxazole was administered orally
      160/800 mg twice daily for 3-7 days, norfloxacin 400 mg b.i.d. for 5 days.
      Analyses of these studies were performed for the intent-to-treat population and
      safety population. The 1298 patients (815 patients with pefloxacin, 404 with
      trimethoprim-sulfamethoxazole, and 79 with norfloxacin) included in the intent-to
      treat-analysis were those with clinical signs and symptoms of acute cystitis and
      significant bacteriuria (>/=10(5) cfu/ml midstream urine) who received a single
      oral dose of pefloxacin or were treated with the control drug. Success rates of
      pefloxacin achieved 4 to 6 weeks after the start of treatment ranged from 65.8%
      to 97.7% for cure or improvement of clinical signs and symptoms and from 53.8% to
      90.5% for bacteriological eradication (trimethoprim-sulfamethoxazole 69.1% to
      92.5% abd 52.1% to 85.1%, and norfloxacin 74.7% and 58.2%, respectively). The
      pooled percentage of patients in whom pefloxacin therapy cured or improved
      clinical symptoms was 82.5% (95% CI: 79.7% to 85.0%). The pooled rate of
      bacteriological eradication was 76.3% (95% CI: 73.2% to 79.2%). The pooled
      success rates of trimethoprim-sulfamethoxazole were 82.7% (95% CI: 78.6% to
      86.2%) for clinical cure or improvement, and 74.3% (95% CI: 69.7% to 78.5%) for
      bacteriological eradication. Testing for equivalence between pefloxacin and
      trimethoprim-sulfamethoxazole in an exploratory sense, the minimal equivalence
      region with significant results was 4.1% points for clinical cure or improvement
      (P < 0.05) and 6.5% points for bacteriological eradication (P < 0.05). Adverse
      events were reported in 235 out of 987 patients treated with pefloxacin. The
      pooled incidence was 23.8% (incidence in individual studies 13.5% to 47.3%). The
      pooled incidence of adverse events associated with the use of the comparative
      drugs was 20.5% (incidence in individual studies 5.9 to 47.7%).

PMID- 18611612
TI  - Clinical efficacy and safety of cefetamet pivoxil in toddlers.
AB  - The safety and efficacy of cefetamet pivoxil, an oral cephalosporin of the third
      generation, have been studied in open, prospective, randomized comparative,
      clinical trials including 301 toddlers (children aged 1 to 2 years) with upper
      and lower respiratory tract infections, and urinary tract infections. Cefetamet
      pivoxil (CAT) syrup formulation was given to 177 toddlers either in the standard
      dose of 10 mg/kg b.i.d. [n = 116] or 20 mg/kg b.i.d. [n = 61] and 124 toddlers
      have been treated with comparator drugs [cefaclor, n = 98;
      phenoxymethylpenicillin, n = 18; amoxicillin plus clavulanic acid; n = 8]. The
      treatment period was 7 days mainly, except for pharyngotonsillitis for which the
      treatment duration was 7 or 10 days. The assessment of treatment was based on
      clinical signs and symptoms primarily in infections of lower respiratory tract
      and acute otitis media, whereas in patients with pharyngotonsillitis and acute
      urinary tract infections the bacteriological findings were the main evaluation
      criteria. The overall therapeutic outcome was successful in 148 (95.4%) of the
      155 toddlers to whom CAT was administered and in 87 (85.3%) out of 102 toddlers
      receiving standard drugs. Adverse events of mild to moderate severity, mainly of
      gastro-intestinal type (vomiting or diarrhoea) occurred in 14.7% in the patient
      group receiving CAT, 11.2% in the toddlers receiving the standard dose of CAT,
      and in 12.9% with the comparator drugs. From the data presented it is concluded
      that cefetamet pivoxil is efficient and safe in toddlers presenting with
      community-acquired respiratory and urinary infections mainly caused by S.
      pneumoniae, H. influenzae, Group A beta-haemolytic streptococci, M. catarrhalis,
      E. coli, Proteus spp. and K. pneumoniae.

PMID- 18611613
TI  - Chemotherapy of varicella zoster virus infections.
AB  - Varicella zoster virus (VZV), a member of the herpesvirus family, is responsible
      for a primary infection (varicella, chickenpox) as well as a recurrent disease
      (zoster, shingles). The course of varicella is generally benign in
      immunocompetent patients. For zoster, post-herpetic neuralgia is the most common
      complication. In immunocompromised patients, particularly patients suffering from
      the acquired immune deficiency syndrome (AIDS), transplant recipients and cancer
      patients, VZV infections can be life-threatening. For these patients and also for
      immunocompetent patients at risk, such as pregnant women or premature infants,
      the current treatment of choice is based on acyclovir (ACV) by either intravenous
      or oral route. The low oral bioavailability of ACV, as well as the emergence of
      drug-resistant virus strains, have stimulated efforts towards the development of
      new compounds for the treatment of VZV infections. Among these new compounds,
      penciclovir (PCV) and its oral prodrug form, famciclovir (FCV), 882C87, BVDU,
      BVaraU and the oral prodrug form of acyclovir (valacyclovir) rank among the most
      promising. Like ACV itself, all these drugs are dependent on the virus-encoded
      thymidine kinase (TK) for their intracellular activation (phosphorylation), and,
      therefore, cross-resistance to these drugs may be expected for those virus
      mutants that are TK-deficient and thus resistant to ACV. However, such TK(-) VZV
      mutants are still sensitive to the acyclic nucleoside phosphonates (i.e. HPMPC),
      which for their phosphorylation do not depend on the virus-encoded TK. The
      molecular targets within the viral replicative cycle, with which these different
      compounds interact, are discussed, as are the in vitro activity and in vivo
      efficacy of the most promising compounds. Other aspects, such as vaccination and
      passive immunization, are briefly mentioned.

PMID- 18611614
TI  - Drug used in the treatment of sleeping sickness (human African trypanosomiasis:
      HAT).
AB  - From the first decade of this century arsenicals have been the most universal and
      most effective drugs for all cases of sleeping sickness. Melarsoprol, introduced
      in the 1940s, remains the most universal of these compounds. However, resistance
      of trypanosomes and toxicity that may be fatal for the patient are two major
      shortcomings. Pentamidine, suramin and Berenil((R)) are active only in the first
      stage of the disease, when the parasites are confined to blood and lymph.
      Nifurtimox taken orally for 1 to 2 months and alpha-difluoro-methylornithine
      (alpha-DFMO) with an administration scheme spread over 5 weeks including 14 days
      of intravenous injections. provide interesting alternatives for all cases, since
      they reach the central nervous system. However, DFMO is known to be less active
      against. T. rhodesiense. Imidazoles, new arsenical derivatives and antimitotics
      have been successfully tested in experimental models. Combinations of drugs with
      additive or pontentiating effects mainly based on inhibition of decarboxylase
      enzymes or exposure to axidative stress appear promising.

PMID- 18611615
TI  - Famciclovir, a new oral antiherpes drug: results of the first controlled clinical
      study demonstrating its efficacy and safety in the treatment of uncomplicated
      herpes zoster in immunocompetent patients.
AB  - This multicentre, double-blind, double-dummy, randomised study was undertaken to
      compare the efficacy and tolerability of famciclovir administered at 250 mg, 500
      mg and 750 mg three times daily with acyclovir 800 mg five times daily for the
      treatment of acute uncomplicated herpes zoster in immunocompetent adults. A total
      of 545 patients participated in this trial. Treatment was initiated within 72 h
      of the onset of the zoster rash and was continued for seven days. When treatment
      was initiated within 72 h, famciclovir was found to be as effective as acyclovir
      at all dose levels for cutaneous lesion healing as demonstrated by the median
      times to full crusting, cessation of new lesion formation, loss of vesicles and
      loss of crusts; time to loss of acute pain was comparable in patients receiving
      famciclovir and acyclovir. Time to resolution of zoster-associated pain, however,
      occured at a significantly faster rate in patients treated with famciclovir
      within 48 h of rash onset compared with acyclovir treatment. Famciclovir was well
      tolerated with a safety profile comparable to that of acyclovir. Gastrointestinal
      disturbances and headache were the most common adverse experiences in all
      treatment groups. In conclusion, famciclovir, administered less frequently and at
      lower unit doses than acyclovir, is an effective treatment for patients with
      uncomplicated herpes zoster.

PMID- 18611616
TI  - Treatment and developmental therapeutics of Mycobacterium avium complex (MAC)
      infections.
AB  - Opportunistic infections associated with AIDS pose very serious problems because
      of their exceedingly high morbidity and mortality. For their part, Mycobacterium
      avium and M. intracellulare, two organisms belonging to M. avium complex (MAC),
      are the most often isolated bacteria from AIDS patients. Although in recent
      years, some progress has been made, by and large, there is no viable drug and /or
      combinations of drugs effective against MAC, especially in AIDS patients.
      Conventional therapies with multiple drug combinations involving isoniazid,
      rifampin, ethambutol, streptomycin, ethionamide, and cycloserine are still widely
      used, as well as prophylactic treatment with rifabutin. The use of clofazimine
      and ciprofloxacin has also been reported. Studies on new quinolones
      (sparfloxacin, difloxacin, WIN 57273), macrolides, folate antagonists and
      antimcobacterial anitbiotics are being actively pursued along with novel
      strategies involving drugs inhibiting mycobacterial cell wall biosynthesis. The
      role of various cytokines in enhancing host immune defenses against MAC
      infections is also discussed.

PMID- 18611617
TI  - Development of an in vitro drug screening system for Mycobacterium leprae based
      on the determination of the intrabacterial sodium to potassium ratio of
      individual bacterial organisms.
AB  - In vitro drug effects on Mycobacterium leprae (M. leprae) in a cell-free system
      have been monitored by mass spectrometric determination of the ratio of the
      intrabacterial concentrations of the sodium and potassium ions (Na(+), K(+)
      ratio) of a limited number of individual bacteria per sample. From the drug
      induced increase of the median values of the distributions of the Na(+), K(+)
      ratio, information on the concentration and time dependence of drug effects as
      well as on antagonistic or synergistic interactions of drugs has been obtained.
      Moreover, absolute values for the percentage of killed bacteria (% kill) have
      been derived from the distribution of the Na(+), K(+) ratios within a bacterial
      population. For this, the limiting value of the Na(+), K(+) ratio (up to which
      bacteria are viable) -which had been determined as 0.45 for cultivable bacteria -
      has been presumed to be valid also for M. leprae. Highest killing rates have been
      observed for fusidic acid and clarithromycin, followed by rifabutine, rifampin,
      and clofazimine. Minocycline and dapsone have shown only moderate killing effects
      and isoniazid and - probably due to the restricted metabolism of M. leprae in a
      cell-free medium - ofloxacin have been completely inactive. Strong ofloxacin
      effects, however, have been observed for cultivable mycobacteria and
      intracellular M. leprae phagocytized by a murine macrophage cell line.

PMID- 18611618
TI  - Activities of liposome-encapsulated azithromycin and rifabutin compared with that
      of clarithromycin against Mycobacterium avium-intracellulare complex in human
      macrophages.
AB  - The activities of liposome-ebtrapped azithromycin, rifabutin or clarithromycin
      against Mycobacterium avium-intracellullare (MAI) were evaluated in a cell model
      of intramacrophage infection. Exposure of free (unencapsulated) and liposome
      encapsulated rifabutin or azithromycin to human monocyte-derived macrophages
      resulted in a marked increase in the uptake of the liposome-entrapped drugs
      compared to the free form. The macrophages were infected at day 7 of culture with
      MAI. Treatment was initiated 24 h following the infection and the surviving
      intracellular bacteria were counted at days 2, 4, and 5. The drugs were used at
      concentrations close to the serum peak levels achievable following administration
      of therapeutic oral doses. The antimycobacterial activity of each of the three
      drugs was significantly enhanced (P < 0.01) when the drugs were delivered in the
      liposome-entrapped form as compared with the effects of the free drugs. Free and
      liposome-encapsulated drugs were used at the same concentrations. With the strain
      of MAI used (ATCC 49601), the efficacy of clarithromycin was significantly bigher
      (P < 0.01) compared to free or liposome-entrapped azithromycin. Also, rifabutin
      either in the free or liposomal form, was markedly more effective than
      clarithromycin. Addition of ethambutol enhanced the efficacies of the three drugs
      whether in the free or liposomal forms. These results suggest that liposome
      encapsulation of rifabutin, azithromycin or clarithromycin may provide the means
      for effective eradication of MAI infections. Further experiments in animal models
      are required to establish the in vivo anti-MAI efficacy of these liposomal
      antimicrobials.

PMID- 18611619
TI  - The BCG controversy.
AB  - The history of tuberculosis control by vaccination with Bacille Calmette-Guerin
      (BCG) is reviewed. Use of the vaccine is evaluated in light of conflicting
      results from trials of BCG efficacy. Explanatinations are suggested for the
      variations between trials, and the continued use of BCG as a vaccine against
      tuberculosis is discussed.

PMID- 18611620
TI  - Invasive group A streptococcal infection: New concepts in antibiotic treatment.
AB  - The incidence of severe group A streptococcal infection and the streptococcal
      toxic shock syndrome has increased since 1986. In contrast to earlier times,
      aggressive streptococal infection is now more likely to affect patients between
      20 and 50 years of age who do not have predisposing underlying diseases. Its
      viral-like prodrome can often mislead clinicians and patients, and nonsteroidal
      anti-inflammatory drugs can mask symptons. Prompt antibiotic therapy is
      mandatory, but even with aggressive treatment mortality may be 30-50%. Though
      penicillin is the drug of choice for most streptococcal infections, its efficacy
      is poor in deep-seated soft-tissue infections, and is in part related to the in
      vivo inoculum effect and 'the physiologic state of the organism'. This paper
      reviews the molecular mechanisms responsible for these phenomena and demonstrates
      the greater efficacy of clindamycin in an experimental model of severe
      streptococcal infection.

PMID- 18611621
TI  - Antifungal activity of a new benzothiazole derivative against Candida in vitro
      and in vivo.
AB  - The antifungal activity of 6-amino-2-n-pentylthiobenzothiazole (APB) against 26
      strains of the genus Candida in vitro was studied. Susceptibility of 17 strains
      was IC(50) </= 40 mumol/ml, of 7 strains IC(50) = 40-80 mumol/ml and of 2 strains
      IC(50) = 80-200 mumol/ml. Generalized candidosis of mice was treated with APB
      (doses 50, 100, 250 mg/kg) and ketoconazole (KET, 50 mg/kg of body weight). The
      optimal dose of APB was shown to be 100 mg/kg; 25% of mice survived after 14 days
      as compared to control animals. C. albicans was not found in the kidney of the
      sacrificed mice. 80% of mice survived after KET therapy. However, C. albicans was
      present in the kidney in an amount of 10(5)-10(6) CFU/g of tissue. C. albicans
      did not reappear in the kidney 7 days after the discontinuation of APB treatment,
      but it was found there after KET therapy.

PMID- 18611622
TI  - Leishmaniasis and itraconazole: a controlled clinical trial on cutaneous
      subtypes.
AB  - Ten patients each with the nodular and ulcerative forms of cutaneous
      leishmaniasis were selected by clinical and pathological criteria. Capsule
      itraconazole was given in a daily dose of 4 mg per kg body weight (max. 200 mg)
      for 6 weeks. Six patients (60.0%) of the nodular and nine patients (90.0%) of the
      ulcerative subgroups were cured by strict clinical and parasitological criteria.
      No major adverse effects were noted. Review after 6 months revealed no
      recurrences. In another ten patients (control group) not receiving any drug, the
      lesions showed no significant change except for one patient demonstrating
      spontaneous remission. Thus, itraconazole has a promising antileishmanial
      potential in India.

PMID- 18611623
TI  - Use of praziquantel against schistosomiasis: a review of current status.
AB  - Praziquantel therapy has become an important component of any programme directed
      towards schistosomiasis control. This disease being prevalent in many
      disadvantaged countries, where the means and resources are limited, the
      strategies for its control on a large scale are also beset with various other
      constraints. In this review, the potentials of praziquantel therapy in containing
      the intensities, prevalences and schistosomiasis-associated morbidities in
      endemic areas of different geographical and epidemiological settings are
      examined. By and large, regular community-based treatment produces a longer term
      favourable impact on infection levels and morbidity, but the impact on the
      disease transmission appears limited. Children constitute a high risk group in
      schistosomiasis. They are usually subjected to more rapid and intense
      reinfection, but they also appear more responsive to praziquantel therapy in
      preventing or reversing the effects of the disease. Modern techniques used in the
      assessment of impact of praziquantel treatment in schistosomiasis control are
      outlined.

PMID- 18611624
TI  - The efficacy of praziquantel for the treatment of cestode and metacestode
      infections.
AB  - The activity of praziquantel against adult and larval cestode infections is
      reviewed. Praziquantel remains an excellent drug for the treatment of taeniasis
      and hymenolepiasis. Neurocysticercosis, however, seems to respond better to a
      treatment with albendazole than to praziquantel, especially when the anthelmintic
      treatment is combined with steroid drugs. Concerning the treatment of hydatidosis
      and coenurosis, more research is needed to evaluate the efficacy of praziquantel.

PMID- 18611625
TI  - Minocycline: old and new therapeutic uses.
AB  - Since the introduction of minocycline HCl in the late 1960's, it has been used
      for disease states that have ranged from typical community-acquired infectious
      diseases to others that are non-infectious, such as resistant rheumatoid
      arthritis. Owing to its high penetration characteristics throughout the body,
      minocycline can be used in the treatment of a wide variety of extracellular and
      intracellular pathogens. This review examines the known and potential therapeutic
      uses of minocycline in a clinical setting.

PMID- 18611626
TI  - A critical review of the dosage of teicoplanin in Europe and the USA.
AB  - The glycopeptide antibiotic, teicoplanin, is increasingly used in Europe in the
      treatment of Gram-positive infection. It is administered as a bolus once daily,
      it has little potential for nephrotoxicity, and serum monitoring is usually
      unnecessary. However, poor results were reported in early trials at a daily dose
      of 200 mg and, more recently, at 400 mg/day in monotherapy of staphylococcal
      endocarditis. While 400 mg (6 mg/kg day(-1)) is now standard, US trials have
      tried very high doses in an attempt to improve its efficacy in monotherapy of
      deep-seated staphylococcal sepsis. European centres continue to use 6 mg/kg day(
      1) as the usual maintenance dose and 6-12 mg/kg as the loading dose. For the more
      difficult cases, teicoplanin is used in combination with other agents. All
      available published and unpublished literature was reviewed to try to solve these
      problems. With the exception of endocarditis, failure rates in the 84 European
      open studies varied more between trials than between the dosages used. In 32
      European and eight US randomized trials, a dose of 6 mg/kg day(-1) of teicoplanin
      was effective, except in staphylococcal endocarditis if teicoplanin was used as
      monotherapy. In that case, 12 mg/kg day(-1) or more was needed to achieve a cure
      rate similar to that of vancomycin. Treatment was most successful with trough
      levels over 20 mg/l. However, lower doses were effective in combination with
      aminoglycosides, as is common in clinical practice. An open trial suggested that
      12 mg/kg day(-1) was needed for treatment of septic arthritis. It is suggested
      that 6 mg/kg day(-1) of teicoplanin be used for all indications except
      staphylococcal endocarditis and septic arthritis when it should be given in a
      dose of 12 mg/kg day(-1) or in combination with other agents.

PMID- 18611627
TI  - Fleroxacin: the newly introduced once-daily quinoline.
AB  - Fleroxacin is a new oral and intravenous trifluoroquinolone with a half-life of
      10-12 h. This new quinolone has excellent bioavailability, good tissue
      penetration, low protein binding and a low rate of metabolism. Serum
      concentrations following oral and intravenous administration are identical,
      allowing the clinician to change comfortably from intravenous to oral therapy.
      Fleroxacin exhibits a broad spectrum af antibacterial activity against aerobic
      Gram-negative bacteria, and also against staphylococci. Comparative clinical
      studies have demonstrated efficacy and safety of fleroxacin as treatment for
      infectious of the urinary and respiratory tract, sexually transmitted diseases,
      infections of the skin and soft tissue and gastrointestinal tract, in a large
      number of adult patients of various ages. These data suggest that fleroxacin will
      be an effective once-daily agent in the treatment of a variety of infections
      caused by bacteria susceptible to this new long-acting quinolone.

PMID- 18611628
TI  - Tissue pharmacokinetics of fleroxacin in humans as determined by positron
      emission tomography.
AB  - The delivery of fleroxacin, a new broad-spectrum fluoroquinolone, to the major
      organs of the body was studied in 12 normal human volunteers (nine men and three
      women), utilizing positron emission tomography (PET). Following the infusion of
      20 mCi of [(18)F]fleroxacin in conjuction with a standard therapeutic dose of 400
      mg, images were acquired over 8 h. Beginning the next day, the subjects received
      unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the
      fifth day. Fleroxacin is distributed widely throughout the body, with the notable
      exception of the central nervous system, with stable levels achieved within 1 h
      after completion of the infusion. Especially high peak concentrations (18 mug/g)
      were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau
      concentrations (2-8 h post-infusion, mug/g) were: brain 0.83; myocardium, 4.53;
      lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87;
      muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35.
      Repetitive dosing had no significant effect on the pharmacokinetics of the drug.
      Since the MIC(90)'s of the family Enterobacterioaceae and Neisseria gonorrhoeae
      are <2 mug/ml, with the great majority of the individual species 1 mug/ml, these
      results suggest that a single daily dose of 400 mg of fleroxacin should be
      effective in the treatment of infections such as urinary tract infection and
      gonorrhea.

PMID- 18611629
TI  - Comparative evaluation of fleroxacin, ampicillin, trimethoprimsulfamethoxazole,
      and gentamicin as treatments of catheter-associated urinary tract infection in a
      rabbit model.
AB  - Fleroxacin, ampicillin, trimethoprim-sulfamethoxazole, and gentamicin were
      comparatively evaluated for effectiveness in treating experimentally induced
      catheter-associated urinary tract infection and bacteriuria in a rabbit model
      with a closed drainage system. Fleroxacin, ampicillin and gentamicin effectively
      eliminated a lactose-negative, streptomycin-resistant uropathogenic strain of
      Escherichia coli (WE6933) from bag urine and catheter port urine, while
      trimethoprim-sulfamethoxazole only marginally reduced urine bacterial counts when
      compared to rabbits that received no antibiotic therapy. Fleroxacin eliminated E.
      coli from the catheter surfaces and from tissues adjacent to the catheter.
      Ampicillin or gentamicin therapy also eliminated biofilm bacteria from the
      catheter surfaces, but did not eliminate th residual bacteria from tissue
      adjacent to the septic catheters despite achieving urine levels of antibiotics
      substantially higher than minimum bactericidal concentrations for this pathogen.
      Trimethoprim-sulfamethoxazole was ineffective in eliminating E. coli from the
      catheter surfaces and the adjacent tissues. The ability of fleroxacin to
      effectively eliminate biofilm bacteria from catheter surfaces and tissues
      adjacent to such medical devices in the urinary tract may prove useful in the
      treatment of catheter-associated urinary tract infection and bacteriuria in
      mammals and humans.

PMID- 18611630
TI  - Quinolones in the treatment of complicated urinary tract infection.
AB  - Complicated and recurrent urinary tract infections present intriguing clinical
      management problems. The underlying conditions in patients with complicated
      urinary tract infections are anatomical abnormalities of the genitourinary tract,
      neurologic disorders resulting in urinary stasis, obstruction, instrumentation,
      surgery, diabeters mellitus, renal transplantation, and renal calculi. In
      comparative studies the quinolones have been shown to be effective in 7-14-day
      treatment courses in complicated urinary tract infection. Several comparative
      trials which compare the fluoroquinolones with beta-lactam antibiotics or
      cotrimoxazole yielded equal or better results for the quinolones. A cost-saving
      option is given with some of the fluoroquinolones that can be administered
      parenterally and orally which enables the patient to be discharged from the
      hospital earlier. There are few differences in antimicrobial activity between the
      newer quinolones, but differences in the pharmacokinetic properties are evident.
      The fluoroquinolones are suitable therapeutics for complicated urinary tract
      infection, because they offer rapid oral absorption, high tissue concentration,
      broad activity against most Gram-negative and Gram-positive organisms, the
      possibility of a once-a-day administration, and relatively few side effects.

PMID- 18611631
TI  - Uncomplicated urinary tract infections - is single-dose therapy effective?
AB  - Short-term therapy, including single-dose treatment and up to 3-day courses, can
      be considered the treatment of choice in female patients with acute uncomplicated
      lower urinary tract infections (UUTI) because of equal effectiveness, better
      tolerance and compliance, and lower cost as compared with conventional therapy.
      Retrospective analysis of several studies with cotrimoxazole, however, suggested
      that results obtained with a single dose may be inferior, and therefore a 3-day
      treatment may be more prudent. Longer therapy was not considered to be necessary.
      On the other hand, studies with substances like fosfomycin trometamol and some of
      the fluotoquinolones, especially when using substances with prolonged half-lives
      such as fleroxacin and pefloxacin, have demonstrated that single-dose therapy is
      as effective as other standard regimens. This controversy may be settled by
      defining the appropriate agents for single-dose as well as those for 3-day
      treatment. Agents which have not been shown to be effective in any of these short
      term regimens should no longer be propagated for the treatment of UUTI. In
      consequence, no further studies using conventional therapy of UUTI are necessary
      in the future.

PMID- 18611632
TI  - Use of fluoroquinolones in lower respiratory tract infections (LRTI).
AB  - In view of their antimicrobial activity and pharmacological properties,
      fluoroquinolens should be suitable for the treatment of lower respiratory tract
      infections - specially of Gram-negative bacterial etiology. These drugs have been
      studied extensively in animal models of respiratory tract infections and found to
      be as efficacious as the comparative drugs - mostly modern betalactam
      antibiotics. In patients, a number of well-controlled randomized studies in lower
      respiratory tract infections (LRT) have been published comparing standard
      treatments (aminopenicillins, tetracyclines, etc.) with new fluoroquinolones. In
      general, the rates of cure and improvement ranged between 82% and 89% for
      enoxacin, ciprofloxacin, ofloxacin and pefloxacin. Fleroxacin has been studied in
      three clinical studied in the treatment of LRTI. It showed the same efficacy as
      the comparators (amoxicillin, ceftazidine) in the treatment of Gram-negative
      LRTI; tolerance data in these studies showed higher incidence of adverse events
      in the fleroxacin group versus the amoxicillin group and similar incidence of
      adverse events in the fleroxacin group versus the ceftazidine group. The numbers
      of premature treatment-withdrawal were low and not significantly different.

PMID- 18611633
TI  - Opportunities for i.v. to oral switch in the management of infections: the role
      of quinolones.
AB  - Quinolones are an important group of drugs for the oral treatment of severe
      infections. We have shown that in patients with bacteremia the serum levels of
      fleroxacin are high enough to treat Gram-negative infections with one single oral
      dose per day. Thus for severe, quinolone-sensitive infections, such as bacteremic
      pyelonephritis, the switch from i.v. to oral may be done even on the first day of
      infection if the patient is not in shock and able to take oral medication.
      Staphylococcal infections have been successfully treated in animal models and non
      randomized human studies with the combination of quinolone and rifampin. We have
      studied the influence of rifampin on the pharmacokinetics of fleroxacin in normal
      volunteers and no dose adjustment appears necessary. A single daily oral dose of
      fleroxacin (400 mg) and rifampin (600 mg) appears to be a promising therapeutic
      approach for staphylococcal infections and is the basis for an ongoing
      prospective randomized clinical trial comparing early switch to oral bitherapy
      with standard i.v. therapy. In conclusion, fleroxacin as a single drug or in
      combination with rifampin is a promising approach for switch from i.v. to oral
      therapy of severe Gram-negative and possibly staphylococcal infections.

PMID- 18611634
TI  - Procedings of the QUINODIS symposium ICC, Stockholm 28 June 1993 Conclusion.

PMID- 18611635
TI  - Implications of fleroxacin's pharmacokinetic profile.
AB  - Fleroxacin, like all quinolones, is well absorbed, reaching peak concentratinos
      within 2 h. Interactions with Ca(2+) and Al(3+) are minimal compared with other
      quinolones and possibly of little clinical importance. The drug is eliminated via
      filtration in the kidney. It is therefore sensitive to changes in renal function.
      Accumulation of dru g in the body is minimal, and change from intravenous to oral
      dosing results in nearly identical serum concentrations. Aside from the modest
      effect of metals on its absorption, fleroxacin does not interact/compete with
      substances oxidized in the liver, such as theophylline, and drug interactions are
      minimal. Its long serum half-life (8-12 h) allows once-a-day dosing. This may be
      of particular pharmacodynamic advantage when treating infections caused by
      organisms with relatively high MIC's. This feature, along with its modest drug
      interactions, indicates that fleroxacin will probably be an important quinolone
      useful in a variety of clinical settings.

PMID- 18611636
TI  - Outpatient treatment with parenteral antimicrobial agents.

PMID- 18611637
TI  - Home intravenous antibiotic therapy (HIVAT): indications, patients and
      antimicrobial agents.
AB  - Concern regarding escalating costs of inhospital intravenous (i.v.) antibiotic
      treatment has stimulated interest in providing i.v. antibiotic therapy in
      outpatient or home settings (HIVAT). HIVAT should be considered when patients no
      longer need careful observation and daily nursing care. Successful HIVAT can be
      accomplished utilizing a team approach emphasizing the respective roles of the
      physician, pharmacist, nurse and patient. This paper is based on a retrospective
      review of approximately 1500 patients (19 500 days of HIVAT), treated between
      1978 and 1993, in a hospital-based programme. This review addresses which
      infectious diseases can be treated with HIVAT, with special emphasis on patient
      and antibiotic selection criteria and the importance of patient monitoring and
      preliminary data on the outcomes of such therapy.

PMID- 18611638
TI  - Outpatient parenteral antibiotic therapy.
AB  - Clinical studies have shown that outpatient administration of parenteral
      antibiotics is sage, cost-effective and practical. The development of new
      antibiotics with prolonged half-lives, such as ceftriaxone or cefotetan, has
      facilitated outpatient parenteral antibiotic therapy (OPAT). Good OPAT management
      requires coordination of physicians, nurses, pharmacists and health care
      administrators, and the establishment of firm guidelines. A variety of infections
      can be treated through OPAT, including osteomyelitis and soft tissue infections,
      chronic urinary tract infections, and ear, nose and throat infections.

PMID- 18611639
TI  - The importance of teamwork for outpatient parenteral antibiotic therapy.
AB  - A variety of treatment models can be constructed to provide intravenous
      antibiotic therapy outside the hospital. The type and details of each model must
      be adapted to local needs and resources, but those that coordinate the resources
      of all the primary members of the team necessary to care for patients, offer the
      greatest potential for a safe and efficient programme. We believe that the
      teamwork of the physician, nurse, and pharmacist in our clinic-based, physician
      directed model can provide a safe and effective service, which is appreciated by
      the patients we care for.

PMID- 18611640
TI  - Kinetics of antibiotics in relation to effective and convenient outpatient
      parenteral therapy.
AB  - An important goal of outpatient parenteral antibiotic therapy (OPAT) is to
      provide a drug and dosing regimen that allows for convenient administration of
      the antibiotic in the outpatient setting. While once-daily administration or
      handling of the drug would be ideal, dosing frequencies up to three times a day
      for intravenous administration and twice daily for intramuscular injection can be
      tolerated by most patients. The frequency and method of antimicrobial
      administration is dependent not only on the kinetics of drug concentrations in
      serum and tissues (i.e pharmacokinetics), but also on the kinetics or time course
      of the drug's antimicrobial activity (i.e. pharmacodynamics). This short review
      will focus on the interaction between pharmacokinetics and pharmacodynamics for
      the major classes of antibacterial agents used for outpatient parenteral therapy.

PMID- 18611641
TI  - Indications for outpatient treatment with parenteral antibiotics in children.
AB  - Serious infections in children can be treated using outpatient parenteral
      antibiotic therapy (OPAT) which is cheaper and less disruptive than
      hospitalization. Responsible and well-informed parents are the key to success of
      OPAT in children, and medical centres should provide suitable follow-up
      procedures. Ceftriaxone is the key drug for various OPAT programmes due to its
      high therapeutic index, lack of toxicity, once-daily administration and good
      intramuscular bioavailablity. However, in some infections other drugs are needed.
      Such parenteral drugs can be used to stabilize the patient before switching to
      oral drugs.

PMID- 18611642
TI  - Benefits of outpatient parenteral antibiotic therapy: to the individual, the
      institution, third-party payers and society.
AB  - The cost of outpatient parenteral antibiotic therapy is outweighed by the
      benefits to all involved: provider, payer, patient and society. Simple
      comparisons of inpatient and outpatient charges are not a true measure of costs.
      Recent in-depth cost-benefit analyses reveal a significant saving when indirect
      benefits, such as increased productivity and quality of life, are included. Even
      so, financial issues remain to be addressed.

PMID- 18611643
TI  - Outpatient treatment with antimicrobial agents: some management concerns.
AB  - As clinicians become more aware of quality of life as a parameter of treatment
      outcome, issues such as the home provision of patient care have become
      increasingly important. While the feasibility of outpatient antimicrobial therapy
      is currently being demonstrated, its development raises a number of important
      policy and economic issues.

PMID- 18611644
TI  - Insurance companies' view on outpatient treatment.
AB  - Now that outpatient treatment of bacterial infections is becoming a clinical
      reality for some patients, many medical insurance companies have expressed an
      interest in the increased patient benefits and reduced costs of this kind of
      patient care. The practicalities of transferring treatment to an outpatient
      setting and the regulations that would surround its initiation are discussed.

PMID- 18611645
TI  - Home treatment and reimbursement in The Netherlands.
AB  - In The Netherlands home care is one of the most rapidly growing fields in health.
      It is thought to provide a cheaper alternative to hospitalization and improved
      quality of life for the patient. However, there is evidence that home care may
      result in better care but does not reduce the burden on hospital services.
      Studies have shown that outpatient parenteral antibiotic therapy (OPAT) is more
      cost-effective, resulting in an improved quality of life. The new home-treatment
      technology requires careful evaluation, under set guidelines, to ensure safety
      and effectiveness.

PMID- 18611646
TI  - Quality, costs and cultural beliefs in outpatient treatment with parenteral
      antibiotics: a comment.
AB  - The introduction of outpatient parenteral antibiotic therapy (OPAT) will change
      the concepts of a hospital and of primary health care. When it is guaranteed by a
      number of general quality conditions, and short-term transformation costs are
      left aside, it has a good chance of developing in cities where distances between
      patient's homes and hospitals are shorter. Cultural beliefs of health care
      providers in hospitals and in primary health care are an important barrier for
      the introduction of OPAT. Perhaps countries with hospital-oriented health care
      systems (Germany, Sweden, USA) will start earlier with OPAT than countries with a
      strong and independent primary health-care system (the UK, Finland and The
      Netherlands). On the other hand, the last three countries are better equipped to
      integrate OPAT into other types of home health service.

PMID- 18611647
TI  - Home care and the general practitioner.
AB  - In the future more patients will be treated at home rather than in hospital.
      Proposed health-care systems have been developed into four scenarios. These have
      been termed the primary care network, primary care centre, transmural network and
      deconstruction. Whatever form it takes, home care must involve cooperation
      between patient, family and health service. A clear description of the duties of
      health professionals is needed, with clear documentation of who is responsible
      for specific care. The general practitioner's involvement should be based on
      specific care programmes to satisfy the patient's care needs.

PMID- 18611648
TI  - The role of the hospital nursing staff in home health-care services.
AB  - Hospital nurses have an important role to play in coordinating the hospital and
      home-care management of patients discharged from hospital. This role becomes even
      more vital with the growing emphasis on transferring part or all of the
      traditional hospital care of some patients to primary carers in the community.
      This policy enables patients to receive treatments as close to their home as
      possible, as well as shortening the number of inpatient days. The aim for primary
      care workers is to take over everyday responsibility for patients receiving
      outpatient antimicrobial treatment, while providing all necessary support from a
      hospital base. For the successful transfer from hospital care to home care, both
      patient and family must be confident in performing the technical medical actions
      required. It is the main responsibility of the nurse to allay any patient fears
      of unforeseen difficulties or problems.

PMID- 18611649
TI  - Indications for home intravenous antibiotic therapy in The Netherlands.
AB  - Advances in technology, such as new antimicrobial drugs and new equipment, have
      led to an increased interest in home intravenous antibiotic therapy (HIVAT) in
      The Netherlands. The aim of this study was to evaluate HIVAT in terms of costs,
      effectiveness and patient experience. Seventy-five patients with an infectious
      disease were treated by a transmural intravenous antibiotic therapy (TIVAT)
      programme at home for approximately 2000 days. An individual protocol and
      training was given to each patient and the care givers so that patients could
      perform the home treatment themselves with, in most cases, the help of family and
      friends. Optimal use was made of existing health care structures like hospital
      facilities, pharmacies and the general practitioner. TIVAT is an example of
      intensive home care. Preliminary data show that it seems safe, effective and cost
      efficient with positive patient experiences. A once-daily dosage regimen of the
      antimicrobial agent was preferable.

PMID- 18611650
TI  - Outpatient treatment in the University Hospital Utrecht: organization and
      infrastructure.
AB  - Interest in home care for patients with serious infections is increasing. Home
      care technology needs reliable equipment that can be operated by the patient
      without constant supervision. To achieve long-term home treatment requires the
      establishment of protocols, education programmes, patient support and easy
      hospital admission. In the present study 185 patients, with cancer or a variety
      of infections, were treated at home over a 2-year period. Nineteen patients who
      had to receive antimicrobial agents were educated for self-administration and
      could contact a health professional with any problems. No serious complications
      due to home treatment with parenteral medication were observed.

PMID- 18611651
TI  - Cystic fibrosis and outpatient treatment with parenteral antibiotics in children.
AB  - Despite recent key insights into the pathogenesis of cystic fibrosis, the
      treatment of patients suffering from this disease remains largely symptomatic.
      Control of respiratory infections is a vital part of patient management,
      involving daily physiotherapy and administration of mucolytics, bronchodilators
      and oral or intravenous antibiotics as necessary. For those patients requiring
      frequent courses of intravenous antibiotics, home treatment appears preferable to
      repeated hospital admissions. A home care programme for cystic fibrosis has been
      running at the Wilhelmina Children's Hospital in Utrecht since 1991, with the aid
      of two specialist nurses to provide support and instruction for children and
      their parents. While parents of younger children were often reluctant to accept
      the increased responsibility for their child's care, children who had received a
      period of home treatment were enthusiastic about its use and eager for the
      programme to continue. However, anxiety of patients and parents and medical
      instability may be of such importance in certain circumstances that treatment is
      not always given at home, even after former successful periods of home care.

PMID- 18611652
TI  - Changing health-care systems.
AB  - Many governments are encouraging competition for resources between health centres
      in an attempt to reduce costs and improve the quality of services. However,
      opponents to managed care believe that this will create more administrative costs
      and reduce patient choice. So-called purchasing organizations are being
      established to direct patients to the most cost-effective care. Assessing
      performance is complicated as very sick or difficult-to-treat patients are likely
      to be more costly. Statistical techniques can be used to clarify the impact of
      risk factors, such as smoking, on the outcome of care.

PMID- 18611653
TI  - Antiretroviral drug interactions.
AB  - It has recently been estimated that persons with the acquired immunodeficiency
      syndrome (AIDS) receive on average 5.6 prescription medications throughout their
      disease course, and this number may be as high as 9 [1,2]. With the development
      and testing of new antiretroviral agents and drugs for opportunistic infections
      associated with human immunodeficiency virus (HIV) disease, the issue of
      polypharmacy and multiple drug interactions will become increasingly complex.
      Since antiretroviral therapy and treatment or prophylaxis of opportunistic
      infections is lifelong, the nature of these interactions requires delineation to
      provide an optimal pharmacologic strategy for the use of these agents in
      combination. This article will address antiretroviral drug interactions from a
      pharmacokinetic and pharmacodynamic perspective. A background on the clinical
      pharmacology of antiretroviral agents is provided as is a discussion of selected
      interactions.

PMID- 18611654
TI  - Cefotiam hexetil.

PMID- 18611655
TI  - The worldwide prevalence of methicillin-resistant Staphylococcus aureus.
AB  - Literature on the occurrence of methicillin-resistant Staphylococcus aureus
      (MRSA) in hospitals and long-term-care facilities in various countries of
      America, Africa, Asia, Australia/New Zealand, and Europe is reviewed. It is
      concluded that the increasing prevalence of MRSA is a worldwide problem,
      affecting both affluent and poor countries, and that infection control guidelines
      are needed in all regions affected.

PMID- 18611656
TI  - Use of antimicrobial drugs in developing countries.
AB  - The era of antimicrobial therapy is now in its seventh decade. The major
      scientific discoveries made during this period have saved of countless lives and
      markedly reduced the morbidity of infectious diseases. These achievements are now
      threatened by the global emergence of resistant strains. The process is fostered
      by the remarkable genetic diversity and transfer of resistance among microbes,
      the selective forces of antibiotic use, and powerful socioeconomic and marketing
      forces. It is doubtful that development of new drugs will adequately address the
      problem. The only measures which might slow the development and transmission of
      resistant microorganisms are those that decrease the global burden of infectious
      diseases. This requires improved sanitation, nutrition and immunization, hospital
      infection control and strategies that will diminish the inappropriate and
      excessive promotion and use of antibiotics. Physicians, pharmacists and consumers
      need to be better informed about how to use antibiotics and the dangers of
      inappropriate use. The multinational and local pharmaceutical companies must
      become more responsible for their products and promotional practices. The current
      situation is bleak. It will undoubtedly will get worse as the burden of resistant
      microorganisms continues to increase.

PMID- 18611657
TI  - Two-hour versus six-hour administration of amphotericin B in the treatment of
      kala-azar.
AB  - In a randomised study, 50 parasitologically confirmed cases of kala-azar were
      allocated to two treatment groups: group A received amphotericin B in 5% glucose
      infusion for 6 h and group B for 2 h. Amphotericin B was given at an initial
      dosage of 0.05 mg/kg body weight, increasing to 1 mg/kg body weight on day 5, and
      this dose was given daily until patients had received a total of 20 mg/kg body
      weight. Toxicities like rise in serum creatinine, fall in serum potassium levels
      and diminution in appetite were no different in the two groups. There was no
      difference in clinical, parasitological and ultimate cures between the two
      groups. Man-hours spent in treating patients in the 2-h infusion group were one
      third of the time with the 6-h infusion group. It was concluded that 2-h infusion
      of amphotericin B caused fewer infusion-related toxicities (shivering and fever)
      and saved time spent in treating patients; hence it should be recommended for
      use.

PMID- 18611658
TI  - Emergence of high-level fluoroquinolone-resistant Escherichia coli in Bangladesh.
AB  - Fifteen fluoroquinolone-resistant strains of Escherichia coli were isolated from
      different clinical specimens of paediatric patients, 2 years after introduction
      of the drugs into Bangladesh. However, none of these patients had any definite
      history of treatment with fluoroquinolones. MICs of these strains to different
      antibiotics were determined by the broth microdilution method recommended by the
      Working Party of BSAC. Strains were highly resistant to all drugs except
      ceftriaxone. Study indicates a high frequency of fluoroquinolone-resistant E.
      coli strains among the clinical isolates which is possibly related to
      fluoroquinolone introduction.

PMID- 18611659
TI  - Potential of clindamycin in addition to vancomycin for the treatment of oxacillin
      resistant Staphylococcus aureus septicemia persisting under vancomycin therapy.
AB  - We observed seven patients with persistent fever and staphylococcemia under
      vancomycin-containing antimicrobial regimens who promptly improved as clindamycin
      was added to the initial antibiotics. Moreover, in all these patients a striking
      increase in peak and trough serum inhibitory activity (SIR) and serum
      bactericidal activity (SBA) levels was observed after addition of clindamycin.
      SIA and SBA levels after administration of a single dose of vancomycin (500 mg),
      clindamycin (600 mg) or vancomycin + clindamycin were also measured in three
      healthy volunteers against six ORSA isolates. Unsatisfactory peak SBA levels (0%
      of cases 1:8) were obtained after vancomycin administration. Vice versa, peak SBA
      levels 1:8 were obtained in 94% of the cases after clindamycin and in 100% of
      cases after vancomycin + clindamycin. Time-kill studies showed a borderline or
      incomplete bactericidal activity of vancomycin against three ORSA isolates from
      infections that manifested poor or slow response to vancomycin therapy. The
      combination with clindamycin did not result in a synergistic interaction between
      the two drugs. It is concluded that addition of clindamycin may be useful in some
      cases of ORSA septicemia that show poor or slow response to vancomycin therapy.
      The recommendation for a wider use of this combination of antibiotics requires
      further documentation of efficacy.

PMID- 18611660
TI  - Meropenem: effects on human leukocyte functions and interleukin release.
AB  - Modifications of the immune response have been reported for a number of
      antimicrobial agents following both in vivo and in vitro experiments. Present
      results were obtained from in vitro incubated human polymorphonuclear cells (PMN)
      and monocytes treated with meropenem, a novel carbapenem antibiotic. Only the
      highest concentrations of meropenem (50-200 microg/ml) significantly reduced the
      phagocytic activity and unstimulated superoxide release of neutrophils after 1 h
      of incubation. Moreover meropenem (100 and 200 microg/ml) reduced PMA-stimulated
      superoxide release by PMN after 1 h of incubation. Only the highest concentration
      used (200 microg/ml) was found to reduce significantly superoxide release by PMA
      unstimulated and -stimulated PMN incubated for 2 h. Meropenem did not affect some
      of the PMN functions studied (killing of Candida albicans, chemotaxis and glucose
      consumption) over a broad range of concentrations (5, 10, 20, 50, 100, 200
      microg/ml). The leukocyte viability did not change even at the highest antibiotic
      concentration used, as showed by the trypan blue exclusion test. The LPS-induced
      release of IL-1alpha, IL-6 and IL-8 from isolated monocytes was not impaired by
      meropenem (100 and 200 microg/ml), that significantly reduced TNFalpha stimulated
      by LPS, after 4 h of incubation. In conclusion our data suggest that
      therapeutically relevant concentrations (5-20 microg/ml) of meropenem did not
      modify substantially the viability and the functions of human leukocytes.

PMID- 18611661
TI  - Interaction of sub-inhibitory concentrations of ciprofloxacin and rifampicin
      against Staphylococcus aureus.
AB  - The frequency of the emergence of ciprofloxacin-resistant mutants to sub
      inhibitory concentrations of ciprofloxacin, rifampicin, and ciprofloxacin plus
      rifampicin were compared in a subcutaneous abscess model of experimental
      Staphylococcus aureus infection in mice. The in vitro findings showed that the
      combination of ciprofloxacin and rifampicin was bacteriostatically additive for
      all strains tested when the combination was examined by the chequer-board
      technique and fractional inhibitory concentration indices determined. Animals
      were infected with ciprofloxacin-sensitive and ciprofloxacin-resistant test
      strains (6989S and 6989R) and left untreated for nine days, which showed that
      ciprofloxacin resistance had no effect on the pathogenicity of the organisms. In
      treated animals, ciprofloxacin plus rifampicin was found to be at least as
      effective as ciprofloxacin alone. However, in the murine model, the combination
      therapy produced significantly fewer high-level ciprofloxacin-resistant mutants
      than ciprofloxacin alone (p<0.0005). We conclude that a combination of
      ciprofloxacin and rifampicin was at least as efficient as either drug alone, and
      the additional presence of rifampicin reduced the emergence of high level
      ciprofloxacin-resistant sub-populations in the case of S. aureus subcutaneous
      abscesses in mice and so the combination may prove to be more efficient than
      ciprofloxacin alone.

PMID- 18611662
TI  - Concentrations of ceftibuten in plasma and the respiratory tract following a
      single 400 mg oral dose.
AB  - Concentrations of ceftibuten in bronchial mucosa, epithelial lining fluid (ELF)
      and alveolar macrophages were determined from samples taken from 15 subjects at
      bronchoscopy following a single 400 mg oral dose. Concentrations at all sites
      were determined using a microbiological assay method which was unaffected by the
      trans-isomer of ceftibuten. The time from dosage to bronchoscopy ranged from 1.4
      to 20.3 h and the subjects were analysed in three groups according to time after
      dosing. Group A had a mean time since dosing of 1.9 h with mean serum, mucosal
      and ELF concentrations of 15.2 mg/l, 5.7 mg/kg and 1.6 mg/l. Group B had a mean
      time of 6.5 h after dosing with mean serum, mucosal and ELF concentration of 14.0
      mg/l, 3.2 mg/kg and 1.6 mg/l. Group C had a mean time of 13.3 h with mean serum,
      mucosal and ELF levels of 4.1 mg/l, 1.8 mg/kg and 1.2 mg/l. Macrophage-related
      ceftibuten could only be detected in two subjects. These levels are related to
      the minimum inhibitory concentrations of ceftibuten against common respiratory
      pathogens with the exception of Strep. pneumoniae.

PMID- 18611663
TI  - Azithromycin: the first of the tissue-selective azalides.
AB  - The azalide azithromycin, which is derived from erythromycin, contains a methyl
      substituted nitrogen in the lactone ring. This 15-membered expanded lactone ring
      results in improved acid stability and oral bioavailability compared with
      erythromycin. Azithromycin possesses a broad spectrum of activity against Gram
      positive and Gram-negative bacteria, including enhanced activity compared with
      the macrolides against Haemophilus influenzae and Moraxella catarrhalis. In vitro
      activity of azithromycin against intracellular and clinically atypical pathogens
      is also good. Azithromycin has a distinct pharmacokinetic profile compared with
      other antimicrobial agents, the most prominent feature is its high tissue
      selectivity. Concentrations of azithromycin in respiratory tract, gynaecological
      tissue and prostate remain above minimum inhibitory concentrations of pathogens
      for several days, thus making it possible to use a short-course, once-daily
      dosing regimen. Another feature of azithromycin is that it rapidly penetrates
      phagocytic cells, with the release of the antibiotics at local sites of
      infection. Comparative clinical trials have shown that azithromycin given once
      daily for 3 or 5 days is comparable to comparator drugs given for 7 or 10 days in
      the treatment of otitis media, sinusitis, pharyngitis, acute bronchitis, acute
      infectious exacerbations of chronic bronchitis, community-acquired pneumonia and
      skin and soft tissue infections in adults. Azithromycin given once daily for 3
      days has also been shown to be effective in the treatment of respiratory tract
      and skin and soft tissue infections in children. In addition, some sexually
      transmitted diseases are effectively treated by a single 1-g dose of
      azithromycin; clinical and microbiological responses were comparable to those
      recorded using doxycycline given twice daily for 7 days. The short-duration, once
      daily dosing regimen is well tolerated in adults and children, and there is no
      evidence of interaction between azithromycin and theophylline, terfenadine, or
      cimetidine.

PMID- 18611664
TI  - A critical review of the in-vitro activity of teicoplanin.

PMID- 18611665
TI  - Antibiotic resistance of bacterial strains isolated from children in Child Health
      Center, Warsaw.
AB  - This study examines the antibiotic susceptibility of 1792 bacterial strains
      isolated from hospitalized children between January and December 1993. A total of
      1015 Gram-negative rods represented by members of Enterobacteriaceae family (770)
      and nonfermenters (245) were isolated. The most resistant strains were noticed
      among Klebsiella pneumoniae and Enterobacter cloacae. From 38% to 46% of K.
      pneumoniae strains were resistant to third-generation cephalosporins, but all of
      them were sensitive to imipenem. From 60% to 80% of E. cloacae isolates were
      resistant to all beta-lactams, but sensitive to imipenem. Resistance of P.
      aeruginosa to aminoglycosides varied from 30% for gentamicin to 5% for amikacin.
      About 40% of P. aeruginosa strains were resistant to carbenicillin, and 25% to
      azlocillin and piperacillin, but only two strains were resistant to ceftazidime
      and imipenem. Among Gram-positive cocci the most frequently encountered were
      coagulase-negative staphylococci, followed by Staphylococcus aureus and
      Enterococcus faecalis. The methicillin-resistant strains of coagulase-negative
      staphylococci and S. aureus consisted 74.8% and 34%, respectively. All strains of
      methicillin-resistant coagulase-negative staphylococci and S. aureus were
      sensitive to vancomycin.

PMID- 18611666
TI  - In vitro activity of loracarbef against common respiratory pathogens compared
      with amoxicillin-clavulanic acid: a multi-centre study in The Netherlands.
AB  - Loracarbef (LC) is the first clinically available carbacephem. In order to
      evaluate the antimicrobial activity of LC, a total of 593 clinical strains of H.
      influenzae, M. catarrhalis, S. pneumoniae and S. pyogenes were collected by seven
      participating study centres. Minimal inhibitory concentrations for loracarbef and
      amoxycillin-clavulanic acid combination (AC) were determined by a microdilution
      method. The MIC-90 of beta-lactamase-negative strains of H. influenzae was 2.0
      (LC) and 0.5 (AC), and for beta-lactamase-positive strains 4.0 (LC) and 2.0 (AC)
      mg/l. For beta-lactamase-negative and beta-lactamase-positive strains of M.
      catarrhalis, the MIC-90 results were 0.5 and 2.0 (LC) and 0.13 and 0.5 (AC) mg/l.
      The MIC-90 for AC was </=0.03 for both S. pneumoniae and S. pyogenes, while the
      LC results were 0.5 and 0.25 mg/l, respectively. Of all strains tested, only one
      beta-lactamase-positive isolate of H. influenzae was shown to be resistant to LC
      and another one to be resistant to AC. The MICs for both AC and LC were
      significantly higher in H. influenzae and M. catarrhalis strains isolated in the
      centre and in the south-east of The Netherlands. In conclusion, the results of
      this study indicate that loracarbef can be used in the initial therapy of
      community acquired respiratory infections.

PMID- 18611667
TI  - Teicoplanin vs. vancomycin for the treatment of serious infections: a randomised
      trial.
AB  - A prospective, randomised study of 56 patients comparing teicoplanin with
      vancomycin for suspected or proven severe Grampositive infection was conducted.
      The majority of infections were soft tissue infections (8 teicoplanin; 16
      vancomycin) and by chance a significantly higher number of Hickman catheter
      related infections occurred in the vancomycin arm (4 vs. 14, P < 0.01).
      Teicoplanin was administered as a single daily dose of 400 mg iv or im; 5
      patients received 200 mg following the initial dose of 400 mg. Vancomycin was
      given 1 g every 12 h. Fifty-four patients were evaluable for efficacy (26
      teicoplanin, 28 vancomycin). Of these, 18 episodes in 17 patients (teicoplanin)
      and 19 episodes in 18 patients (vancomycin) gave an evaluable clinical response,
      the success rates being similar (76% teicoplanin; 68% vancomycin). Staphylococcus
      aureus was the most common pathogen isolated; all pathogens were susceptible to
      both glycopeptides with MICs < 4 mg/l. Bacteriological elimination rates were
      similar in both groups (71% teicoplanin; 78% vancomycin). Significantly more
      patients given vancomycin experienced adverse events (7 teicoplanin; 16
      vancomycin; P = 0.03). This caused treatment to be discontinued in 4 cases,
      compared with only one receiving teicoplanin. The most common vancomycin-related
      events were histamine-associated reactions (15 patients), including 2 cases of
      Red Man Syndrome, and nephrotoxicity (5 patients). There were no histamine
      mediated events and only one case of nephrotoxicity with teicoplanin. Teicoplanin
      and vancomycin show similar clinical and bacteriological efficacy and teicoplanin
      is significantly less toxic and easier to use in patients with severe infection.

PMID- 18611668
TI  - Cefotaxime-resistant Gram-negative bacilli in a University Hospital: occurrence,
      identity, source and sensitivity patterns.
AB  - Of the Gram-negative bacilli isolated at The Royal Free Hospital between October
      1993 and February 1994, 2.6% (73 2806 ) were not fully sensitive to cefotaxime,
      giving zone diameters in disk tests indicating MIC of cefotaxime > 8 mg/l. Most
      were Enterobacter spp. (27) or Pseudomonas aeruginosa (21), from leukaemic
      patients or sputa. Eight-four percent were sensitive to imipenem. Resistance to
      ceftazidime or aztreonam was reversed more frequently by tazobactam or sulbactam
      than by clavulanate.

PMID- 18611669
TI  - Sequences related to Tn1331 associated with multiple antimicrobial resistance in
      different Salmonella serovars.
AB  - Serovars of Salmonella resistant to ampicillin, third-generation cephalosporins
      and aminoglycosides but sensitive to chloramphenicol, cefoxitin and ceftibuten
      emerged in one pediatric hospital of Buenos Aires. All isolates expressed AAC(6')
      I and AAC(3)-V enzyme activities, making them resistant to all aminoglycosides
      marketed in Argentina by the time this investigation was performed. The
      cefotaxime resistance marker, the AAC(3)-V enzyme activity and Tn1331-related
      sequences were associated with plasmid DNAs from different Salmonella serovars.

PMID- 18611670
TI  - Brucellosis.

PMID- 18611671
TI  - Pharmacology and clinical use of foscarnet.
AB  - Foscarnet, licenced by Astra pharmaceutical products, is a pyrophosphate analogue
      that selectively inhibits replication of viruses in infected cells. It inhibits
      in vitro the replication of all herpes viruses, including human cytomegalovirus
      (HCMV) at concentrations of 100 to 300 mumol/l and has a dose-related inhibitory
      effect on HIV-1 virus, influenza virus and hepatitis B virus. It does not require
      intra-cellular phosphorylation for antiviral activity. Oral bioavailability of
      foscarnet is low (12-22%), and foscarnet must be administered intravenously. It
      is mainly eliminated unchanged by the kidneys. Mean half-life in plasma ranges
      from 3.4 to 5 h. For acute therapy, the currently recommended regimen is 60 mg/kg
      t.i.d. or 90-100 mg/kg b.i.d. In AIDS patients, foscarnet is an effective
      treatment of HCMV retinitis. Healing or stabilisation of lesions is obtained in
      85-95% of patients after 2 weeks or 3 weeks therapy. For HCMV gastrointestinal
      disease, complete or partial response rates of 57-95% have been reported with
      foscarnet. The optimal maintenance dosage of foscarnet necessary in CMV
      infections in AIDS patients remains to be clearly established. Data from small
      samples size studies have shown that foscarnet decreased significantly
      circulating levels of HIV antigen in AIDS patients with HCMV disease. Foscarnet
      is an effective treatment for acyclovir-resistant herpes simplex virus and for
      acyclovir-resistant varicella-zoster virus (40 mg/kg every 8 h). In patients with
      immunosuppression not HIV-related HCMV infections, particularly interstitial
      pneumonia in transplant recipients, experience with foscarnet is limited. The
      major adverse effect of foscarnet is reversible renal dysfunction, due to acute
      tubular toxicity. In may be partially prevented by hyperhydratation during the
      treatment. Fluctuations in serum calcium and phosphore levels, with both increase
      and decrease are also frequent adverse reactions. Most clinical symptoms are
      related to decrease in ionized calcium levels. Hyperphosphatemia, a clinically
      benign phenomenom, reflects the incorporation of foscarnet in bone. Penile
      ulcerations have been described and may result from mococutaneous direct toxicity
      of foscarnet eliminated in urine. Although relapses frequently occur after a few
      months of maintenance therapy, foscarnet that shows a marked activity against
      HCMV in vitro, has allowed important progress in therapy of HCMV infections in
      AIDS patients.

PMID- 18611672
TI  - Itraconazole for the treatment of histoplasmosis and blastomycosis.
AB  - Itraconazole is a triazole compound with broad-spectrum antifungal activity which
      includes the pathogenic yeasts, certain Aspergillus species, and the endemic
      fungi such as Histoplasma capsulatum and Blastomycosis dermatitidis. Although
      prospective trials comparing itraconazole to other azoles and amphotericin B are
      unavailable, recently published data suggest that itraconazole is the drug of
      choice for patients with mild to moderate histoplasmosis and blastomycosis
      without central nervous system involvement. Among patients with the acquired
      immunodeficiency syndrome and histoplasmosis, itraconazole has emerged as an
      effective alternative to amphotericin B for induction therapy in selected
      patients, and has largely replaced amphotericin B for chronic maintenance therapy
      in these patients. For patients with severe or life-threatening histoplasmosis or
      blastomycosis and for patients with central nervous system involvement,
      amphotericin B remains the initial therapy of choice.

PMID- 18611673
TI  - Arbekacin.

PMID- 18611674
TI  - Oral cephalosporins: current perspectives.
AB  - Oral cephalosporins had been, for years, a small group of compounds belonging to
      the first or second-generation cephalosporins, with a limited antimicrobial
      spectrum. New oral first-generation cephalosporins include cefprozil and
      loracarbef, similar to cefadroxil and cefaclor, respectively, with activity
      similar to cefaclor but with pharmacokinetic improvements. Second-generation oral
      cephalosporins are esters of already available cephalosporins, and third
      generation oral cephalosporins include a number of drugs whose activity is
      similar to available parenteral drugs, showing pharmacokinetic advantages and,
      some of them, better resistance to hydrolysis mediated by extended wide-spectrum
      beta-lactamases. They may be a good alternative against mild to moderate ENT
      infections, UTIs, STDs, lower respiratory tract and skin and soft tissue
      infections, mainly in the outpatient setting.

PMID- 18611675
TI  - Quality and bioavailability of tetracycline capsules in a Nigerian semi-urban
      community.
AB  - Six batches of tetracycline capsules were purchased from different dispensing
      points in Ile-Ife, a Nigerian semi-urban town and subjected to weight uniformity
      tests, microbiological assay and chromatographic determination of degradation
      products. Four of them were also subjected to dissolution tests and a comparative
      bioavailability study. A batch of capsules obtained from the local manufacturer
      of the innovators product was used as the reference standard. From this study, it
      is apparent that the tetracycline capsules available in this locality are of poor
      pharmaceutical quality. This has led to poor relative availability and may have
      made some contribution to the high level of tetracycline resistance in the sample
      environment.

PMID- 18611676
TI  - In vitro activity of WY-49605, a penem antimicrobial.
AB  - The in vitro activity of the penem antimicrobial WY-49605 was compared with those
      of other agents available for oral administration. Based on concentrations
      inhibiting 90% of isolates (MIC(90)s), the penem inhibited methicillin
      susceptible staphylococci (MIC(90) = 0.25 microg/ml), penicillin-susceptible
      streptococci (MIC(90) < or = 0.12 microg/ml) and several other Gram-positive
      genera at concentrations comparable or superior to the most active comparison
      agents. WY-49605 and cefpodoxime were the most active agents against members of
      the family Enterobacteriaceae. Most strains of Enterococcus faecalis and
      Bacteroides fragilis were susceptible to the new agent at concentrations < or
      =4microg/ml, while Pseudomonas aeruginosa, Enterococcus faecium, and methicillin
      resistant Staphylococcus aureus were resistant to all agents tested.

PMID- 18611677
TI  - A study of the interaction between recombinant bactericidal permeability
      increasing protein (rBPI(23)) and gentamicin.
AB  - rBPI(23) is a recombinant protein based upon the N-terminal sequence of
      bactericidal permeability increasing protein (BPI), a protein present in the
      granules of polymorphonuclear leukocytes. BPI has antibacterial activity against
      Gram-negative organisms and potent endotoxin neutralising properties. rBPI(23)
      has been developed as a potential agent for use in Gram-negative sepsis and has
      completed phase 1 clinical trials. In this study a broth microdilution
      chequerboard method has been used to investigate the interaction between rBPI(23)
      and gentamicin, an antibiotic used in a similar clinical setting. Using organisms
      with a range of inherent susceptibilities to rBPI(23), additive or synergistic
      effects were seen which tended to be proportional to the sensitivity to rBPI(23)
      alone.

PMID- 18611678
TI  - Treatment and experimental therapeutics of blastomycosis.

PMID- 18611679
TI  - Factors affecting methicillin resistance in Staphylococcus aureus.
AB  - Methicillin resistance in staphylococci is primarily due to the methicillin
      resistance determinant which produces an additional low affinity penicillin
      binding protein PBP2'. Expression of PBP2' is controlled by its own regulatory
      element, and shares also the same induction system as beta-lactamases. However,
      methicillin resistance levels do not correlate with the amount of PBP2' produced,
      but are determined by the strain specific genetic background. These factors
      responsible for high methicillin resistance have not yet been characterised.

PMID- 18611680
TI  - Resistance patterns in Turkey.
AB  - Resistance to antimicrobial agents in Gram-positive and Gram-negative bacteria is
      common in Turkey. In this review, resistance to several antimicrobial agents in
      this country is discussed for bacteria which have gained clinical importance in
      recent years. Among Gram-positives, staphylococci are of major importance because
      of their high level of resistance to many agents in the hospital and the
      community. Methicillin resistance in different hospitals ranges from 13% to 37%.
      High-level resistance to gentamicin occur in enterococci and resistance to
      glycopeptides have not been reported in these isolates. S. pneumoniae resistance
      to penicillin have been observed in Turkey as 47% in Hacettepe University and
      most of the resistant isolates were from children with severe underlying
      diseases. In reports from other hospitals, the level of resistance was lower
      because of a different patient population. In Gram-negative bacilli,
      aminoglycoside resistance is a significant problem in the treatment of severe
      infections in our country. The most common mechanism of resistance in our
      isolates is the plasmid-mediated enzymatic modification of these agents. Extended
      broad spectrum beta-lactamases have been detected in Klebsiella spp. and
      Salmonella spp. in Turkey. In a Pseudomonas strain, an extended-spectrum variant
      of OXA-10 was identified. Some isolates were also shown to produce plasmid
      mediated PER-1 enzymes. Due to resistance problems encountered in many hospitals,
      restriction control measures have been started in some hospitals in order to
      limit the antibiotic use and our hope is the country-wide application of these
      precautions as soon as possible.

PMID- 18611681
TI  - A sequential study of intravenous and oral Fleroxacin for 7 or 14 days in the
      treatment of complicated urinary tract infections.
AB  - OBJECTIVE: To compare 1 and 2-weeks of sequential intravenous and oral treatment
      for complicated urinary tract infection. DESIGN: Randomized, clinical trial.
      SETTING: 2 secondary and 1 tertiary care hospital in the Netherlands. PATIENTS:
      Patients (54) were randomly assigned, after 3 days Fleroxacin 400 mg iv once
      daily, to receive oral fleroxacin (400 mg OD,) either during 4 (total 7) days (n
      = 26), or during 11 (total 14) days (n = 28). Thirty-four patients were evaluable
      for efficacy. Complicated urinary tract infection was defined as the presence of
      an anatomical or functional abnormality of the urinary tract, urinary tract
      instrumentation, patients presenting with clinical signs and symptoms of
      pyelonephritis or a serious illness such as diabetes mellitus, immunosuppression
      or renal failure. Complicated urinary tract infection was defined as the presence
      of an anatomical or functional abnormality of the urinary tract, urinary tract
      instrumentation, patients presenting with clinical signs and symptoms of
      pyelonephritis or a serious illness such as diabetes mellitus, immunosuppression
      or renal failure. RESULTS: A bacteriological cure was seen in 22 of 34 (65%)
      patients at 4-6 weeks after therapy. Overall, a favorable bacteriological
      response was obtained in 26 of 34 (76%) patients. No significant difference could
      be found among the two dosage groups (7 days: 14 18 = 78 %; 14 days: 12 16 = 75
      %). CONCLUSIONS: Sequential iv and oral treatment with fleroxacin in complicated
      UTI is a satisfactory treatment modality. Larger trials should be done in a more
      homogeneous population, studying shorter treatment durations in complicated UTI.

PMID- 18611682
TI  - Antibiotic susceptibility of staphylococcal isolates from patients with vascular
      catheter-related bacteremia: potential role of the combination of minocycline and
      rifampin.
AB  - The antimicrobial susceptibility to ten antibiotics of 197 staphylococcal
      isolates recovered over a 10-year period from patients with vascular catheter
      related bacteremia was examined. Isolated organisms induced methicillin-sensitive
      Staphylococcus aureus (95 isolates), methicillin-resistant S. aureus (42
      isolates) and methicillin-resistant S. epidermidis (60 isolates). A microtiter
      assay was used to determine the MIC and MBC of individual antibiotics and to
      conduct time-kill studies of certain drug combinations. The activity of
      clidamycin, cefamandole and oxacillin was generally restricted to methicillin
      sensitive organisms, whereas daptomycin, novobiocin, teicoplanin and vancomycin
      exhibited bactericidal activity against all tested staphylococcal species.
      Bacterial resistance to ciprofloxacin was detected among the more recent isolates
      of methicillin-resistant staphylococci. Minocycline and rifampin demonstrated
      bacteriostatic and bactericidal activity, respectively, against all groups of
      organisms. The interaction of rifampin with minocycline, vancomycin, or
      novobiocin was generally indifferent. The results of this study support the
      ongoing efforts for evaluation of the antimicrobial efficacy of vascular
      catheters coated with the combination of minocycline and rifampin.

PMID- 18611683
TI  - Penicillin-resistant Streptococcus pneumoniae in Riyadh, Saudi Arabia.
AB  - During a period of ten months, minimum inhibitory concentrations (MICs) to seven
      antimicrobial agents of 150 clinical isolates of Streptococcus pneumoniae were
      determined at a teaching hospital in Riyadh, Saudi Arabia. Twenty-two (14.7%)
      isolates showed relative resistance to penicillin. High-level resistance to
      penicillin was not observed in any of the isolate. Seventeen (11.3%) isolates
      were resistant to erythromycin, and 31 (20.7%) to tetracycline. Multiple
      resistance was observed in 21 (14%) isolates. Decreased resistance to ceftriaxone
      was also found in two (1.3%) isolates. Isolates with relative resistance to
      penicillin were significantly associated with higher rates of resistance to other
      antibiotics than were penicillin-susceptible isolates. This was also true for
      multiple resistance encountered in both groups.

PMID- 18611684
TI  - Value of culture of pus via percutaneous drainage under sonographic guidance in
      diagnosis and therapy of pyogenic liver abscess.
AB  - Pyogenic hepatic abscess is often a serious disease, whose rates of cure are
      proportional to the timeliness of treatment and the correct use of antibiotics.
      The final choice of antibiotics should be guided by the results of a culture.
      Local cultures of pus are more often positive than blood cultures It is essential
      to plan an effective treatment regimen when dealing with immunocompromised
      patients. Our results, regarding 85 patients with pyogenic liver abscess, 19 of
      which were immunocompromised, seen at our Department from 1980 to 1992, indicate
      that planning the therapy on the base of blood culture alone means a 78% risk of
      inappropriate treatment.

PMID- 18611685
TI  - In vitro influence of polyunsaturated fatty acids on nosocomial Pseudomonas
      aeruginosa: a preliminary report.
AB  - Recent evidence derived from a mouse infection model implies an 'anti-infective'
      role of polyunsaturated fatty acids (PUFAs) which could not be attributed to an
      alteration of eicosanoid or cytokine biosynthesis provoked by them. In order to
      investigate that role, seven Pseudomonas aeruginosa nosocomial pathogens were in
      vitro exposed to 200 and 300 mug/ml of two PUFAs, arachidonic acid (AA) and gamma
      linolenic acid (GLA), by performing 43 time-kill curves. Both PUFAs were found to
      inhibit P. aeruginosa growth as compared to their controls, an effect maximized
      at 5 h of incubation and minimized at 24 h. The strains that survived after the
      24 h AA and GLA exposure were removed from the culture medium with added AA or
      GLA; half of these strains acquired enormously higher MIC and MBC values to
      aminoglycosides compared to their relevant controls. The possible mechanism of
      action of AA and GLA on P. aeruginosa and the clinical relevance of the presented
      findings is a matter of further research.

PMID- 18611686
TI  - Detection of an integrated tetracycline-resistance plasmid in Staphylococcus
      aureus from a Nigerian hospital.
AB  - The genetics of tetracycline-resistance determinants was studied in eight
      methicillin-resistant and two methicillin-sensitive Staphylococcus aureus
      isolated from a Nigerian hospital. Curing and transfer experiments demonstrated
      that one methicillin-sensitive S. aureus isolate WBG4762, had a 4.4 kb
      extrachromosomal plasmid- as well as a chromosomally-mediated tetracycline
      resistance. All others had chromosomal tetracycline resistance and were resistant
      to either tetracycline and minocycline or tetracycline only. The two methicillin
      susceptible isolates were resistant to both tetracycline and minocycline.
      Chromosomal DNA from all the resistant isolates hybridized with a digoxigenin-11
      dUTP labeled 4.4 kb tetracycline-resistance plasmid probe indicating that they
      contained tetracycline-resistance plasmids similar to the probe integrated into
      their chromosomes. The results demonstrated the presence of integrated
      tetracycline-resistance plasmid in both methicillin-resistant and methicillin
      susceptible S. aureus resistant to tetracycline and minocycline as well as those
      resistant only to tetracycline. This is the first demonstration of an integrated
      tetracycline-resistance plasmid in methicillin-sensitive S. aureus and suggests
      that the integrated tetracycline-resistance plasmid may be widespread in S.
      aureus.

PMID- 18611687
TI  - Resistance to antimicrobial agents as a public health problem: importance of the
      use of antibiotics in animals.

PMID- 18611688
TI  - Management issues in paediatric pharyngitis and otitis media.
AB  - Pharyngitis and otitis media are among the most common infections of childhood.
      Both conditions are associated with a range of complications, lead to
      considerable morbidity and place a burden on healthcare systems. Antibiotics are
      the current mainstay of treatment for these infections, with beta-lactams being
      the agents most commonly used. This review examines a range of issues in the
      management of pharyngitis and otitis media, particularly recent developments in
      antimicrobial therapy.

PMID- 18611689
TI  - The value of culture of pus via percutaneous drainage under sonographic guidance
      in diagnosis and therapy of pyogenic liver abscess.
AB  - Pyogenic hepatic abscess is often a serious disease, whose rates of cure are
      proportional to the timeliness of treatment and the correct use of antibiotics.
      The final choice of antibiotics should be guided by the results of a culture.
      Local cultures of pus are more often positive than blood cultures. It is
      essential to plan an effective treatment regimen when dealing with
      immunocompromised patients. Our results, regarding 85 patients with pyogenic
      liver abscess, 19 of which were immunocompromised, seen at our Department from
      1980 to 1992, indicate that planning the therapy on the base of blood culture
      alone means a 78% risk of inappropriate treatment.

PMID- 18611690
TI  - Ofloxacin and fleroxacin enhance superoxide production in human polymorphonuclear
      leukocytes by increasing phosphorylation in the signal transduction pathway.
AB  - Many antimicrobial agents including new quinolones (NQs) influence the cellular
      defense mechanisms such as polymorphonuclear leukocytes (PMNs), macrophages and
      lymphocytes. We examined the effects of NQs on superoxide (SO) production of PMNs
      following stimulation of phorbol myristate acetate (PMA). Ofloxacin (OFLX) and
      fleroxacin (FLRX) significantly augmented SO production of PMNs compared to
      lomefloxacin, sparfloxacin. Staurosporin and H-7, specific inhibitors of protein
      kinase C of SO production pathway in PMNs, inhibited augmented SO production by
      OFLX and FLRX in the concentration-dependent manner. NADPH oxidase activity was
      not influenced by OFLX in cell lysate assay system. These results suggest that
      OFLX and FLRX augmented PMN function through enhancing protein kinase activity,
      but not through direct enhancement of NADPH oxidase.

PMID- 18611691
TI  - Trends in the susceptibility to antimicrobial drugs of common pathogens in
      childhood septicaemia in Nigeria: experience at the University of Maiduguri
      Teaching Hospital, Nigeria, 1991-1994.
AB  - From 1991 to 1994, Staphylococcus aureus, untyped Coliform spp. and Salmonella
      spp., other Enterobacteriaceae and other bacteria were isolated from 40.7%,
      37.6%, 19.5% and 2.2%, respectively, of 225 confirmed cases of septicaemia in
      postneonatal infants and children. Overall, 98.9%, 72.8%, 70.8%, 87.9%, 4.3%,
      79.3%, 42.6%, 17.6% and 40.6%, respectively, of pathogens were sensitive to
      oflaxacin, ceftazidime, cefuroxime, amoxicillincavulante, ampicillin, gentamicin,
      erythromycin, cotrimoxazole, and chloramphenicol. The resistance of S. aureus to
      ceftazidime and cloxacillin, and of Enterobacteriaceae to cefuroxime, has
      increased but multi-drug resistance is apparently not a major problem presently.
      Chloramphenicol has remained clinically an effective treatment for enteric fever,
      despite the high prevalence of in vitro resistance, and should remain the drug of
      choice. The sustained effectiveness of gentamicin should make it useful for
      combination with either a potentiated broad-spectrum penicillin or a second or
      third-generation cephalosporin for the treatment of septicaemia including those
      situations in which the causative bacteria has not yet been identified.
      Oflaxacin, although not normally recommended for use in children, could be a
      potential 'rescue' drug should multi-drug resistance become a serious problem;
      more clinical experience with its use in children is urgently needed.

PMID- 18611692
TI  - Resistance of some selected pathogens to antimicrobials in Hungary.
AB  - Bacterial resistance is an increasingly severe problem in Hungary. According to
      the data from Peterfy Teaching Hospital, Budapest and from the country-wide
      network of Public Health Laboratories, penicillin resistant pneumococci,
      multiresistant Enterobacteriaceae and Pseudomonas aeruginosa are of major
      concern. Over 30% of pneumococci are penicillin resistant. The proportion of
      methicillin resistant Staphylococcus aureus is relatively low nation-wide (6.2%)
      but at Peterfy hospital it is higher (30%). The rate of resistance of Pseudomonas
      aeruginosa against gentamicin, tobramycin is about 30-40%, while that against
      amikacin (11%) ceftazidime (11.9%) and imipenem (5%) remained low. The resistance
      of Pseudomonas aeruginosa against ciprofloxacin is rapidly increasing, exceeding
      50% in some hospital departments. The high bacterial resistance appears to be the
      consequence of the unconsidered use of antibiotics and poor infection control in
      hospitals.

PMID- 18611693
TI  - Survey of the levels of antimicrobial resistance in Argentina: WHONET program-
      1991 to 1994.
AB  - The World Health Organization has implemented an international program of
      antibiotic resistance survey, called WHONET, with the participation of 121
      laboratories from 41 countries around the world. Argentina joined WHONET program
      in 1989. Five hospitals from Buenos Aires are taking part, under the coordination
      of the National Institute of Microbiology 'Dr. C. Malbran'. From the results
      obtained between 1991 and 1994, the low level of susceptibility to
      aminopenicillins, cephalosporins and aminoglycosides is remarkable. On the other
      hand, vancomycin-resistant Enterococcus spp. and Staphylococcus spp. have not
      been detected and imipenem resistance in Pseudomonas aeruginosa, and
      Acinetobacter spp. isolates has not overcome 7% and 11%, respectively. Analytical
      programs utilizing these data aid in the understanding of the epidemiology of
      antibiotic resistance and in the development of rational antibiotic prescription
      practices and infection control procedures.

PMID- 18611694
TI  - 2-Amino diphenylsulfides as new inhibitors of trypanothione reductase.
AB  - Trypanothione reductase (TR) is the primary enzyme responsible for the reduction
      of trypanothione, the analog of glutathione found in trypanosomatidae. We have
      discovered a series of diphenylsulfides which are potent inhibitors of TR and
      have no activity on mammalian glutathione reductase. These compounds are also
      active in vitro on various stages of the parasite. Although structurally related
      to phenothiazines, which are known to be TR inhibitors, these compounds are
      devoided of any neuroleptic activity, making them attractive leads to develop
      specific and non toxic anti-chagasic drugs.

PMID- 18611695
TI  - Absorption of ciprofloxacin in febrile and afebrile patients.
AB  - There are few studies evaluating the effect of fever on the bioavailability of
      oral antimicrobials. Owing to the growing interest in early conversion of febrile
      hospitalized patients from intravenous to oral therapy to reduce costs and avoid
      line sepsis, we evaluated the absorption of a single 500 mg dose of ciprofloxacin
      in 12 patients during an acute febrile episode and following defervescence.
      Patients able to take medication by mouth, oral temperature > or = 38.9 degrees
      C, and no known gastrointestinal disease were enrolled. Medications known to
      interact with the test agent were discontinued. Serum samples were obtained prior
      to and up until 12 h postdose. Pharmacokinetic parameters were obtained from the
      concentration-time profile using noncompartmental methods. The mean values for
      C(max) were 2.45 +/- 0.77 and 2.31 +/- 1.26 microg/ml, for T(max) 1.48 +/- 0.75
      and 2.48 +/- 1.46 h, AUC(0-->infinity) 10.91 +/- 3.64 and 11.05 +/- 4.41
      microg/ml h, and T (1 2 ) 4.05 +/- 0.65 and 4.08 +/- 0.76 h, respectively, for
      the febrile and afebrile periods. No statistically significant differences were
      observed between these parameters. We conclude that oral ciprofloxacin is well
      absorbed and is a suitable alternative to intravenous therapy in selected
      patients during an acute febrile illness.

PMID- 18611696
TI  - DNA gyrase gyr A gene mutations in ofloxacin-resistant Staphylococcus aureus.
AB  - A total of 106 clinical isolates of Staphylococcus aureus were classified into
      nine pattern types correlated with gyrA mutations. In 62 strains, mutations were
      found at a single codon (84, 85, 86 and 88), while 22 strains showed double
      mutations either at codons 84 and 85 or at codons 84 and 88. The double mutations
      led to the highest levels of ofloxacin resistance (MIC, > or = 128 microg/ml).
      All isolates with a single Ser-84--> Leu change had an ofloxacin MIC of 8-128
      microg/ml, whereas others showed an MIC range of 8-16 microg/ml. Twenty-two wild
      type strains and one strain with a single mutation at codon 86 (silent mutation)
      were ofloxacin-susceptible. Thus, gyrA mutations seem to play a definite role in
      the high-level of resistance to ofloxacin.

PMID- 18611697
TI  - Epidmiology and management of systemic fungal infection. Introduction.

PMID- 18611698
TI  - Epidemiology of mycoses in the HIV-infected patient: clinical aspects.
AB  - Among the major problems confronting patients with AIDS are opportunistic fungal
      infections. Primary infections include candidiasis, cryptococcosis, the major
      endemic mycoses, and aspergillosis. The endemic mycoses of AIDS consist of
      Histoplasma found mostly in the U.S. and Latin America, Coccidioides in parts of
      Latin America and the southwest U.S., Penicillium marneffei in Thailand and other
      parts of southeast Asia, and Blastomyces worldwide. The latter, however, has so
      far been rare in AIDS. The major endemic mycoses tend to target patients very
      late in AIDS, with CD4 counts commonly below 100. Diagnosis is usually made by
      characteristic morphology of the fungal elements as seen at microscopy, and the
      pathogens are readily cultured from infected tissues, and in the case of
      Histoplasma, from blood.

PMID- 18611699
TI  - Current clinical issues on mycoses in neutropenic patients.
AB  - Invasive fungal infections, which are associated with high morbidity and
      mortality rates, are an increasing challenge for the management of
      immunocompromised hosts, particularly neutropenic cancer patients. Due to the
      ageing population, recent progress in cancer therapy and better prognosis of
      bacterial infections, the numbers of patients at risk of life-threatening mycoses
      are increasing. The percentage of cancer patients with evidence of an invasive
      fungal infection ranges from approximately 5% to 30%. The most common
      opportunistic fungal pathogens are Candida spp. and Aspergillus spp. but recently
      unusual pathogens including Fusarium, Trichosporon and many others have been
      increasingly reported. Although some progress has been made in the last decade,
      several controversial issues need to be addressed by clinicians as well as by
      medical microbiologists and mycologists involved in the care of patients
      experiencing fungal infections. A comprehensive clinical strategy, such as that
      initiated under the auspices of EORTC is a meaningful approach to ensure high
      quality clinical research in that field in order to define guidelines for more
      effective diagnosis, prevention and treatment approaches of invasive fungal
      infections in cancer patients at the European level.

PMID- 18611700
TI  - Epidemiological shifts in opportunistic and nosocomial Candida infections:
      mycological aspects.
AB  - Increases in the prevalence of yeast species other than C. albicans as agents of
      disseminated mycoses in immunosuppressed patients and of fluconazole-resistant C.
      albicans isolates from patients infected with HIV indicate changes in the
      epidemiology of Candida infections. The precise reasons for alterations in
      prevalence of various agents are difficult to pinpoint but changes in the types
      of host populations at risk of Candida infection and selection of resistant yeast
      populations by widescale usage of certain antifungal agents seem to be factors
      involved in the process. Greater attention to speciation of clinical yeasts and
      standardized susceptibility test methods are needed for future epidemiological
      surveillance.

PMID- 18611701
TI  - Resistance of clinically important yeasts to antifungal agents.
AB  - Resistance of yeasts to antifungal agents was a relatively minor clinical problem
      for many years. Recently Candida albicans isolates resistant to fluconazole have
      been reported with increasing frequency in the setting of oral infections in HIV
      positive patients. Improved standardization of fluconazole susceptibility testing
      has resulted in demonstrable correlations between yeast resistance in vitro and
      in vivo for this agent in the AIDS setting. Known resistance mechanisms for azole
      antifungals include reduced access of the drug to the intracellular sterol
      demethylase target, probably because of the action of multidrug resistance efflux
      pumps, and overproduction of that target. Management and prevention of future
      resistance development requires greater vigilance for surveillance than has been
      the practice in the past.

PMID- 18611702
TI  - Antifungal prophylaxis in neutropenic patients.
AB  - Although a number of studies have been published on antifungal prophylaxis in
      neutropenic and bone marrow transplantation patients, there are a lot of
      conflicting data. Some of this may be due to a lack of consensus on the
      definition of fungal disease and the definition of end-points for treatment. The
      risk factors associated with fungal infection, the causative species and the
      antifungals currently used for prophylaxis are reviewed. Future trends in
      prophylaxis, such as the use of growth factors and peripheral blood stem cells
      are discussed.

PMID- 18611703
TI  - Oral candidiasis: the clinical challenge of resistance and management.
AB  - Oral candidiasis is a common fungal infection in patients with an impaired immune
      system, such as those undergoing chemotherapy for cancer and patients with AIDS.
      It has a high morbidity amongst the latter group with approximately 85% of
      patients being infected at some point during the course of their illness. A major
      predisposing factor in HIV-infected patients is a decreased CD4 T-cell count. The
      majority of infections are due to C. albicans although other species such as C.
      glabrata, C. tropicalis, C. krusei and C. parapsilosis are increasingly isolated.
      The systemic azoles, ketoconazole, fluconazole and itraconazole, have been an
      important benefit in treatment. To date, resistance has primarily been a problem
      with fluconazole in AIDS. However, it is important that measures are instituted
      to prevent the spead of resistant strains and the development of cross
      resistance. Although the NCCLS has established a reference method to measure in
      vitro susceptibility, besides already published papers, more data are necessary
      to demonstrate that resistance correlates with clinical failure.

PMID- 18611704
TI  - Aspergillosis: diagnosis and treatment.
AB  - The incidence of invasive aspergillosis is increasing rapidly in the developed
      world with two Aspergillus spp., A. fumigatus and A. flavus, causing the majority
      of infections (85-90% and 5-10%, respectively). The major risk factors are
      profound neutropenia (< or =1000 x 10(6) cells/L), prolonged neutropenia,
      neutrophil function deficits, and corticosteroid therapy. Useful diagnostic
      techniques include sputum culture, CT scan, bronchoscopy with microscopy and
      culture, percutaneous lung biopsy, open lung biopsy and serology. Invasive
      aspergillosis has an almost 100% mortality rate if untreated. Amphotericin B is
      the usual first-line therapy although it is associated with a high failure rate.
      Itraconazole (> or =400 mg daily) is a useful alternative and surgical resection
      may be life saving in some cases. The efficacy of the initial therapy is critical
      for improving mortality rates.

PMID- 18611705
TI  - Cryptococcal meningitis: diagnosis and treatment.
AB  - In the last decade, largely due to the increasing number of immunocompromised
      patients, particularly those with AIDS, there has been a dramatic increase in the
      incidence of cryptococcosis. The majority of human cryptoccoccal infections are
      caused by C. neoformans. Pulmonary cryptococcosis is the commonest form of
      infection and meningitis is the most severe, being fatal in most cases. Diagnosis
      is usually by culture and/or serology. Combined therapy with amphotericin B and
      flucytosine remains the initial treatment of choice, although a short course of
      amphotericin B alone followed by high dose fluconazole or itraconazole and the
      combination of flucytosine with fluconazole or with itraconazole may be effective
      alternatives. Both azoles, given as single agent maintenance therapy, have been
      shown to be beneficial as they are more effective and less toxic than the weekly
      infusion of amphotericin B. Primary prophylaxis with fluconazole has been
      advocated but problems of resistance are a concern. To date, itraconazole has not
      been associated with problems of resistance.

PMID- 18611706
TI  - Itraconazole: pharmacology, clinical experience and future development.
AB  - Itraconazole is an orally active, broad-spectrum, triazole antifungal agent which
      has a higher affinity for fungal cytochrome P-450 than ketoconazole but a low
      affinity for mammalian cytochrome P-450. Itraconazole has a broader spectrum of
      activity than other azole antifungals and shows interesting pharmacokinetic
      features in terms of its tissue distribution. These properties have resulted in
      reduced treatment times for a number of diseases such as vaginal candidiasis, as
      well as effective oral treatment of several deep mycoses, including aspergillosis
      and candidiasis. Currently itraconazole is registered in 42 countries for the
      treatment of systemic fungal infections. Further development is concentrating on
      antifungal prophylaxis as well as on an oral solution and an intravenous
      formulation.

PMID- 18611707
TI  - Open-label titration study of the safety of RMP-7 in patients with the acquired
      immune deficiency syndrome.
AB  - RMP-7, a nine-amino acid bradykinin analogue, has been shown in animals to
      temporarily increase the permeability of the blood brain barrier to small
      molecules including amphotericin B, when administered intravenously. We sought to
      evaluate the safety of escalating doses of RMP-7 administered to human volunteers
      with the acquired immune deficiency syndrome (AIDS). Six HIV antibody-positive
      adults with CD4+ cell counts <50/mm3 received three increasing doses of RMP-7 on
      successive days: 30 ng/kg, 100 ng/kg and 300 ng/kg infused over 2, 2 and 10 min,
      respectively. Adverse experiences were dose-related, mild-moderate in intensity,
      primarily related to vasodilation and resolved rapidly without sequelae. Mean
      maximum increases in pulse rate at 30 ng/kg, 100 ng/kg and 300 ng/kg were 4.0,
      7.8 and 28.2 beats per min, respectively. The maximum changes in average mean
      arterial pressure were +7.7, +5.6 and -0.2 mmHg from baseline, respectively.
      Minor increases in liver enzymes were noted in three patients, all with pre
      existing enzyme elevations. Despite the high frequency of both occult and overt
      cardiovascular abnormalities in advanced HIV infection, RMP-7 is shown to be safe
      in this group of AIDS patients at all dosage levels tested, with adverse effects
      similar to previous experience in healthy humans.

PMID- 18611708
TI  - Griseofulvin and its uses.
AB  - Griseofulvin has been used in the treatment of dermatophyte infections for the
      past 30 years. The use of the drug in treating other medical conditions is
      reviewed.

PMID- 18611709
TI  - Antibody response to tetravalent influenza subunit vaccine in patients infected
      with human immunodeficiency virus type 1.
AB  - The capacity of patients infected with human immunodeficiency virus (HIV) to
      develop an adequate antibody response to influenza vaccination in relation to the
      CD4 cell count has been studied in a prospective study. A total of 73 subjects
      (54 HIV-infected patients and 19 healthy control persons) were vaccinated with
      influenza subunit vaccine containing 15 mug hemagglutinin of each of the
      following strains: A/Beijing/353/89(H3N2), A/Singapore/6/86(H1N1),
      B/Panama/45/90, and B/Beijing/1/87. Hemagglutinin inhibition (HI) antibody titers
      were determined prior to vaccination, 3 weeks afterwards, and at the end of the
      influenza season. The percentage of subjects with HI antibody titers above the
      assumed protective level was significantly lower in the HIV-infected patients for
      all 4 vaccine strains compared with those in the control group (7-26% and 42-74%,
      respectively). There was an association between CD4 cell count and antibody
      response to the B/Panama strain only. The serologic response to tetravalent
      subunit influenza vaccine is severely impaired in the majority of HIV-infected
      patients compared with control subjects. The results of this study challenges the
      recommendation to vaccinate HIV-infected patients.

PMID- 18611710
TI  - Comparative in vitro activity of l-ofloxacin and FK037 to other agents against
      10,040 fresh clinical isolates.
AB  - Fresh clinical isolates collected from November 1, 1992 through November 1, 1993,
      were tested by agar dilution against 26 different antimicrobial agents including
      FK037 and l-ofloxacin. Among the 10 040 organisms tested were Staphylococcus
      aureus (n = 1222), methicillin-resistant Staphylococcus aureus (MRSA, n = 455),
      Staphylococcus epidermidis (n = 533), Staphylococcus hominis (n = 90),
      Staphylococcus hemolyticus (n = 89), Streptococcus pneumoniae (n = 144),
      Escherichia coli (n = 2326), Klebsiella pneumoniae (n = 745), Enterobacter
      cloacae (n = 258), Proteus mirabilis (n = 445), Pseudomonas aeruginosa (n = 998),
      and Stenotrophomonas (Xanthomonas) maltophilia (n = 102). Both l-ofloxacin and
      FK037 inhibited 98% of S. aureus strains at 4 mug/ml. FK037 was at least 4 times
      more effective than the third generation cephalosporins against MRSA, inhibiting
      79% of the strains at 16 mug/ml. While the potency of these agents looks
      promising, their clinical utility will depend in part upon the maximal dosage
      that can be safely administered.

PMID- 18611711
TI  - 'In vitro' development of metronidazole, erythromycin, amoxicillin and gentamicin
      resistance in Helicobacter pylori.
AB  - Serial passage of 37 Helicobacter pylori clinical isolates on increasing
      concentrations of metronidazole rapidly produced five strains with MICs up to 512
      fold higher than those for the original strains. For these five metronidazole
      resistant strains the MICs of erythromycin, gentamicin and amoxicillin were
      unchanged. When they were submitted to the same technique for these last
      antimicrobial agents, only one strain developed high level resistance to
      erythromycin and gentamicin having MIC values respectively up to 32 and 64-fold
      increased. Finally, no amoxicillin-resistant Helicobacter pylori could be
      obtained.

PMID- 18611712
TI  - Antibacterial activity of hydroxychalcone against methicillin-resistant
      Staphylococcus aureus.
AB  - Anti-candidal hydroxychalcone, 2,4,2'-trihydroxy-5'-methylchalcone (THMC), was
      investigated for its antibacterial activity against methicillin-resistant
      Staphylococcus aureus (MRSA). THMC showed the minimum inhibitory concentrations
      of 25.0-50.0 mug/ml against tested 20 strains, at which the effect was based on a
      bacteriostatic action. THMC of 25.0 mug/ml completely inhibited the incorporation
      of radio-labelled thymidine and uridine into MRSA cells. In combination with
      antibiotics, the fractional inhibitory concentration indices were 0.47 for
      gentamicin and 0.79 for vancomycin, indicating that THMC acts synergistically
      with these agents. THMC would be a potent therapeutic agent for MRSA infections.

PMID- 18611713
TI  - Comparative trial of 3-day azithromycin versus 10-day amoxycillin/clavulanate
      potassium in the treatment of children with acute otitis media with effusion.
AB  - A randomized, open clinical trial was performed to compare azithromycin and
      amoxycillin/clavulanate potassium in children with acute otitis media with
      effusion. Patients were allocated to therapy with azithromycin (10 mg/kg once
      daily for 3 days) or amoxycillin/clavulanate potassium (40 mg/kg/day divided into
      three equal doses for 10 days). Clinical examination and tympanometric evaluation
      were performed at baseline, and at day 3 to 5, day 10 to 14, day 28 to 30 and day
      55 to 60 after the initiation of therapy. Tympanocentesis fluid cultures were
      collected at enrolment, and urine and blood samples were obtained at baseline and
      at day 10 to 11. Of 100 patients enrolled, 92 were considered evaluable. Middle
      ear cultures were positive in 53.2% of the patients; the most common pathogens
      were Streptococcus pneumoniae (33%) and Haemophilus influenzae (33%). The
      response was satisfactory in 47 (100%) patients treated with azithromycin and 42
      (95.4%) patients receiving A/C. Rates of persistence of middle ear effusion were
      comparable. Nausea and loose stools were more common in children treated with
      amoxycillin/clavulanate potassium (P < or = 0.02). Based on the comparable
      efficacy noted in this study, the lower incidence of side-effects and the
      convenience of a shorter duration of treatment, azithromycin represents an
      attractive therapeutic alternative to amoxycillin/clavulanate potassium and
      should be further evaluated in larger-scale clinical trials including patients
      with penicillin-resistant organisms.

PMID- 18611714
TI  - Sulbactam and clavulanic acid: enzyme kinetics and synergy with ampicillin and
      mezlocillin.
AB  - The two beta-lactamase inhibitors, sulbactam and clavulanic acid, exhibit high
      affinity (K(I) < 10(-6)mol/l) for the beta-lactamases of Gram-negative organisms
      with predominantly penicillinase activity and much less affinity (especially
      clavulanic acid) for organisms with predominantly cephalosporinase activity. In
      tests to compare the synergy of these beta-lactamase inhibitors with other
      antibiotics, clavulanic acid and ampicillin or mezlocillin demonstrated greater
      synergy than sulbactam and ampicillin or mezlocillin, with isolates forming
      either a plasmid-coded beta-lactamase or a chromosomal enzyme with predominantly
      penicillinase activity. However, neither sulbactam nor clavulanic acid were able
      to protect ampicillin or mezlocillin adequately against inactivation by beta
      lactamase overproducing variants of Klebsiella pneumoniae or Klebsiella oxytoca,
      irrespective of the extent of synergy seen with the corresponding wild strains.
      It was interesting to note the synergy between mezlocillin and sulbactam with
      respect to beta-lactamase overproducing variants of clinical isolates of
      Enterobacter cloacae. A statistically significant correlation between the
      quantities of beta-lactamase formed and synergy between the beta-lactamase
      inhibitor and the antibiotic with which it was combined was not retained in
      studies of clinical isolates in any case. These observations correlate well with
      the results obtained in routine testing of the combinations of
      amoxycillin/clavulanic acid and ampicillin/sulbactam.

PMID- 18611715
TI  - The influence of sulbactam on the in vitro activity of mezlocillin, piperacillin
      and cefotaxime.
AB  - In a multicentre study, the in-vitro activity of mezlocillin (MEZ, Chemical
      Abstract Service [CAS] 51481-65-3), piperacillin (PIP, CAS 61477-96-1) and
      cefotaxime (CTX, CAS 63527-52-6) against mezlocillin-resistant organisms was
      determined alone and in combination with the beta-lactamase inhibitor sulbactam
      (SBT, CAS 68373-14-8). A total of 870 strains were investigated (481
      Enterobacteriaceae, 57 Pseudomonas aeruginosa, 41 Acinetobacter spp., 194
      Bacteroides fragilis and 97 Staphylococcus spp.). MIC values were determined
      using the agar dilution test (aerobic organisms) or the microbroth dilution test
      (Bacteroides spp.) in accordance with Deutsche Industrie fur Normung 58 940. SBT
      was added in fixed concentrations of 5 mg/l and 10 mg/l. For all combinations
      with SBT investigated, the geometric mean of the MIC and the MIC(50) and MIC(90)
      values were reduced as compared with the antibiotic alone (without SBT).
      Consequently, the proportion of sensitive strains was appreciably increased, for
      example in the Enterobacteriaceae: MEZ 1%, MEZ + 10 mg/l SBT 53%; PIP 4%, PIP +
      10 mg/l SBT 54%; CTX 52%, CTX + 10 mg/l SBT 68%. The effect of SBT was especially
      pronounced on Bacteroides spp. For this organism, the proportion of sensitive
      strain rose from 2% to 97% (MEZ), 6% to 95% (PIP) and from 7% to 98% (CTX). The
      results show that adding SBT appreciably enhances the activity of MEZ, PIP and
      CTX against resistant strains of microorganism, and extends the activity spectrum
      to include anaerobic organisms. Thus the availability of SBT as a single-agent
      preparation for use in combination with various beta-lacta antibiotics represents
      a worthwhile enlargement of the therapeutic armamentarium for treating bacterial
      infections.

PMID- 18611716
TI  - The effect of a combination of ampicillin and sulbactam against clinical isolates
      of anaerobic bacteria.
AB  - The antimicrobial susceptibility of 196 recent clinical isolates of anaerobic
      bacteria to ampicillin alone, ampicillin plus 1 mug/ml sulbactam, ampicillin plus
      5 mug/ml sulbactam, and cefoxitin was studied by means of agar dilution tests.
      The ampicillin/sulbactam combination was most effective against species of the
      Bacteroides fragilis group, the minimum inhibitory concentration (MIC)(90) of
      ampicillin plus 5 mug/ml sulbactam for B. fragilis being 1 mug/ml, compared with
      256 mug/ml of amoicillin, 4 mug/ml of ampicillin plus 1 mug/ml sulbactam, and 8
      mug/ml of cefoxitin. No significant difference between ampicillin alone and in
      combination with sulbactam was observed against Gram-positive anaerobic rods or
      cocci.

PMID- 18611717
TI  - Stability of beta-lactamase inhibitors and beta-lactam antibiotics in parenteral
      dosage forms and in body fluids and tissue homogenates: a comparative study of
      sulbactam, clavulanic acid, ampicillin and amoxycillin.
AB  - The beta-lactamase inhibitors and the beta-lactam antibiotics differ appreciably
      in chemical stability. A comparative study of four different infusion solutions
      at 4, 25 and 37 degrees C yielded the following descending sequence of stability:
      sulbactam (CAS 68373-14-8), ampicillin (CAS 69-53-4), amoxycillin (CAS 61336-70
      7) and clavulanic acid (CAS 58001-44-8). Especially noteworthy was that the two
      beta-lactamase inhibitors, sulbactam and clavulanic acid, behaved very
      differently. Moreover, sulbactam is markedly more stable than clavilanic acid
      even when incubated at 37 degrees C in body fluids or tissue homogenates. The
      differences in the chemical stability of these pharmacological agents should be
      taken into consideration in the therapeutic use of combination preparations such
      as sulbactam/ampicillin (Unacid(R)) and clavulanic acid/amoxycillin.

PMID- 18611718
TI  - Pharmacokinetics of ampicillin/sulbactam in patients undergoing colorectal
      surgery: measurements in serum, the colonic wall and in tissue at the incision
      site.
AB  - The concentrations of ampicillin and sulbactam were determined in serum, colonic
      wall and incision site tissues from 23 patients undergoing elective colorectal
      surgery after infusion of a high-dose regimen (2 g ampicillin/1 g sulbactam) or a
      low-dose regimen (1 g ampicillin/0.5 g sulbactam). The results confirmed that
      ampicilin and sulbactam penetrated well into the tissues studied and reached
      therapeutically effective concentrations at the various sites. The high dose
      regimen showed higher concentrations of both compounds in serum and tissues,
      indicating a longer period of perioperative protection against bacterial
      pathogens. Thus, about 39 min after the end of the infusion of the high-dose
      regimen, the mean concentration of ampicillin was 68.8 +/- 31.2 mug/g and of
      sulbactam 23.4 +/- 6.3 mug/g in the tissue of the colonic wall. Low-dose
      prophylaxis, showing mean tissue concentrations of ampicillin of 35.6 +/- 7.0
      mug/g and of sulbactam of 14.2 +/- 2.4 mug/g about 48 min after the infusion, is
      appropriate if the duration surgery does not significantly exceed 2 h.

PMID- 18611719
TI  - Treatment of bacterial infections in children with sultamicillin.
AB  - Infections caused by beta-lactamase-producing pathogens should be treated with
      beta-lactamase-stable antibiotics or with penicillin-derivatives in combination
      with inhibitors. Sulbactam, which acts as a beta-lactamase inhibitor, works in
      conjunction with ampicillin by extending the spectrum of ampicillin to include
      ampicillin-resistant germs. Sultamicillin is an active substance that combines
      sulbactam and ampicillin to form an ester. Sultamicillin's bio-availability
      remains high even after eating. For children, the dosage is 50 mg/kg/day, in two
      doses. The prospective study of 100 patients of between 6 months and 12 years of
      age with respiratory, skin, and mucous membrane infections produced a therapy
      success rate of 90%. The most significant side-effects were exanthemas and
      diarrhoea.

PMID- 18611720
TI  - Sulbactam in combination with mezlocillin, piperacillin or cefotaxime: clinical
      and bacteriological findings in the treatment of serious bacterial infections.
AB  - An open, multicentre study was performed in hospital in-patients at a total of 12
      German hospitals to investigate the efficacy and tolerability of sulbactam
      combined with mezlocillin, piperacillin or cefotaxime in severe bacterial
      infections. A total of 155 patients were recruited into the study, of whom 48
      were suffering from respiratory tract infections, 66 from intra-abdominal
      infections, 34 from skin/soft tissue infections including postoperative wound
      infections, and five from complicated urinary tract infections. Fifty-five
      patients intravenously received 4 g mezlocillin and 1 g sulbactam three times
      daily, 52 received 4 g piperacillin and 1 g sulbactam three times daily, and 48
      received 2 g cefotaxime and 1 g sulbactam three times daily. The antibiotic and
      sulbactam combination was administered in all cases by rapid intravenous infusion
      of both components together, over 20 min. The mean duration of treatment was 20
      days. The criteria used to define the outcome of treatment as successful were
      clinical cure (complete disappearance of the signs and symptoms of infection seen
      before the start of treatment) or improvement (appreciable diminution or partial
      resolution of the initial signs and symptoms, no further antibiotic therapy
      required) and the elimination of the organisms isolated before the start of the
      study. Of the 153 clinically evaluable patient, 141 (92%) were classed as
      responders (a cure was obtained in 98 cases and improvement in 43 cases). No
      response to the study medication was seen in 12 patients (7.8%). The response
      rates of the combined antibiotic-sulbactam preparations were 91% for
      mezlocillin/sulbactam, 92% for piperacillin/sulbactam, and 93% for
      cefotaxime/sulbactam. These response rates are almost identical. A total of 106
      patients (68.4%) were bacteriologically evaluable; a total of 192 bacterial
      organisms were identified in these patients before the start of treatment. Mixed
      infection was present in 55 patients. The causative organism initially isolated
      was eliminated in 96 patients (90%), accounting for 180 of 192 strains (94%).
      Persistence of the causative organism (12 strains) was seen in eight patients
      (7.6%). Superinfection (four strains) was seen in two patients (1.9%). The study
      medication was well tolerated; adverse drug effects were seen in only five
      patients (3.3%). Treatment was discontinued in one patient because of the adverse
      effect (exanthema). The combination of the beta-lactamase inhibitor sulbactam and
      a ureidopenicillin or cefotaxime was highly effiacious in patients with severe
      bacterial infections investigated in this study. The availability of sulbactam as
      a single-agent preparation opens up new avenues for flexible and cost-effective
      antibiotic therapy and is a valuable contribution to the control of bacterial
      resistance.

PMID- 18611721
TI  - Efficacy and safety of sultamicillin (750 mg bid) compared with
      amoxycillin/clavulanate (625 mg tid) in patients with umcomplicated urinary tract
      infections.
AB  - In an open, randomized, multicentre study, two aminopenicillin/beta-lactamase
      inhibitor combinations for oral administration were compared in 132 out-patients
      with umcomplicated urinary tract infections. Two groups of 66 patients each
      received a dose of 750 mg sultamicillin (STM) bid or 625 mg
      amoxycillin/clavulanic (AMX/CLA) acid tid. The evaluation of efficacy was
      performed on a total of 126 patients (STM: 64, AMX/CLA: 62) in whom bacteria were
      isolated before the start of treatment. In the STM group, 61 patients (95.3%)
      were treated successfully (cure and elimination of the organism), versus 56
      patients in the AMX/CLA group (90.3%). Both combinations were well tolerated;
      troublesome adverse effects were not seen. Sultamicillin is an efficacious
      treatment for acute urinary tract infections, like AMX/CLA. Moreover, whereas STM
      is as efficacious as AMX/CLA, and is as well tolerated, it has the advantage of
      requiring only twice-daily dosing.

PMID- 18611722
TI  - Sulbactam/ampicillin versus cefoxitin in the treatment of gynaecological
      infections: an antibiotic therapeutic study.
AB  - Seventy-six women with gynaecological infections such as endometritis,
      salpingitis, tubo-ovarian abscess and pelvic peritonitis were treated with
      sulbactam/ampicillin (SBT/AMP) (50% of patients) or cefoxitin (CFN) (50% of
      patients) in a randomized, controlled study. The diagnosis was based on the
      history, clinical findings and microbiological culture findings. The disease was
      assumed to be of bacterial origin if leukocytosis was present with a left shift
      or if the causative organism was identified. Of the group of patients treated
      with SBT/AMP, 33 (87%) were cured and 4 (10.5%) showed improvement; 1 patient
      (2.5%) failed to respond to treatment. The equivalent figures for the CFN group
      were: 30 patients (79%) cured, 4 (10.5%) showed improvement and 4 (10.5%) failed
      to respond to treatment. The causative organism was eradicated in 29 (91%)
      patients in the SBT/AMP group and 20 (59%) patients in the CFN group. Reinfection
      occurred in 1 (3%) patient in the SBT/AMP group and 4 (12%) patients in the CFN
      group. The causative organism persisted in 1 (3%) patient in the SBT/AMP group
      and 4(12%) patients in the CFN group. The superiority of SBT/AMP in
      microbiological terms was statistically significant, but the superiority of
      SBT/AMP in terms of clinical efficacy was not. The combination of SBT and AMP was
      efficacious and well tolerated in the treatment of gynaecological infections.
      This combination offers the advantage of being effective against Streptococcus
      faecalis and beta-lactamase producing organisms.

PMID- 18611723
TI  - Comparison of sulbactam/ampicillin and cefuroxime in infections of the lower
      respiratory tract: results of a prospective, randomized and comparative study.
AB  - In a randomized, prospective study, ampicillin (AMP) in combination with the beta
      lactamase-inhibitor sulbactam (SBT) was compared with cefuroxime (CXM) in 73
      hospitalized patients with lower respiratory tract infections. Of these patients
      36 received SBT/AMP 1 g/2 g tid and 37 received CXM 1.5 g tid - both in the form
      of intravenous infusion. The duration of treatment ranged from 5 to 12 days, with
      a median of 8 days in each group. In the SBT/AMP group, 23 patients (64%) had
      pneumonia, while 13 (36%) had acute purulent bronchitis; 13 of the patients (36%)
      received artificial respiration. In the CXM group, 23 patients (62%) had
      pneumonia and 14 (38%) acute purulent bronchitis; eight patients (22%) required
      artificial respiration. In 54 patients (SBT/AMP: 26; CXM: 28), initial culture
      yielded bacterial pathogens, mainly Escherichia coli, Haemophilus influenzae,
      Klebsiella pneumoniae, Staphylococcus aureus and pneumococci. In each group, 35
      patients were clinically evaluable. Of the patients receiving SBT/AMP, 31 (89%)
      responded to treatment and 28 patients (80%) responded to treatment with CXM.
      Four patients (11%) who received SBT/AMP failed to respond, as did seven patients
      on CXM. The bacteriological efficacy was assessed in 26 patients in the SBT/AMP
      group: in 22 cases (84%) baseline pathogens were eradicated, while in two
      patients (8%), there was persistent infection and a superinfection, respectively.
      In 23 patients (82%) of the CXM group (28 patients evaluated), the pathogens were
      eradicated, while three cases (11%) had persistent infection, and two (7%)
      superinfection. Apart from a case of exanthema under CXM, no adverse drug
      reactions were reported. No statistically significant differences were seen
      between the two groups. SBT/AMP proved to be a safe and effective alternative to
      CXM in the treatment of lower respiratory tract infections in hospitalized
      patients.

PMID- 18611724
TI  - Which antibiotic is better for the treatment of infections of the lower
      respiratory tract?
AB  - The efficacy and tolerance of mezlocillin and ampicillin/sulbactam were
      investigated in an open, comparative, multicentre study involving 96 patients.
      The high levels of efficacy of both ampicillin/sulbactam and mezlocillin, as
      previously documented in comprehensive in vitro studies, were confirmed with
      regard to the wide range of pathogens examined in this study. Both therapies were
      also associated with high clinical success rates and were well tolerated. It is
      worth noting that the larger number of patients suffering from chronically
      obstructive bronchitis apparently had no negative effects on the clinical results
      of the ampicillin/sulbactam therapy. In cases of nosocomial respiratory tract
      infections, especially those with a high incidence of beta-lactamase-producing
      organisms, a combination including beta-lactamase inhibitors may be expected to
      be superior to any of the ureido penicillins. The present study demonstrates that
      in cases of community acquired infections of the lower respiratory tract,
      treatment with ampicillin/sulbactam can be regarded as a suitable therapeutic
      alternative to mezlocillin, combining high efficacy and tolerance.

PMID- 18611725
TI  - Perioperative use of ampicillin/sulbactam, cefoxitin and
      piperacillin/metronidazole in elective colon and rectum surgery: a prospective
      and randomized quality control study in 422 patients.
AB  - As previous work has shown, antibiotic prophylaxis is highly effective in
      lowering wound infection rates in colorectal surgery. In order to establish
      quality control, the authors investigated the effectiveness of three different
      prophylactic antibiotic regimes in 422 patients in a prospective and randomized
      trial. There were no significant differences between the three groups with regard
      to age, type of operation and risk factors like adipositas and diabetes. The
      wound infection rate according to the Centers for Disease Control criteria ranged
      from 7.0% to 9.5%. No significant difference was found between the three
      antibiotic regimes. It can be concluded, therefore, that under the conditions
      used in this study each of the three different types of antibiotics is of equal
      value, hence, the cheapest one can be used.

PMID- 18611726
TI  - Comparative in vitro studies on the beta-lactamase-inhibiting effect of
      clavulanic acid and sulbactam on ampicillin-resistant Enterobacteriaceae.
AB  - Clavulanic acid and sulbactam alone are ineffective against Pseudomonas and
      enterococci. Staphylococci and Enterobacteriaceae are inhibited by high
      concentrations not attainable under clinical conditions. Strains of
      Acinetobacter, especially A. lwoffii are susceptible to clavulanic acid and
      highly susceptible to sulbactam. The ampicillin/sulbactam combination is superior
      to ampicillin/clavulanic acid against Citrobacter freundii, Enterobacter spp. and
      Morganella morganii. The latter combination is superior against Klebsiella spp.
      and Escherichia coli. Antagonistic effects are more frequent with the clavulanic
      acid combination (Enterobacter spp. and C. freundii) but are rarely observed with
      the sulbactam combination (Providencia spp. and P. rettgeri).

PMID- 18611727
TI  - Preface.

PMID- 18611728
TI  - Evolution of the antimicrobial susceptibility of B. fragilis group at the
      university hospital of Seville (Spain) between 1977 and 1995.
AB  - A susceptibility survey of the B. fragilis group divided into three periods was
      carried out between 1977 and 1995 at the University Hospital of Seville (Spain)
      using the agar dilution method. No chloramphenicol, imipenem or meropenem
      resistant strains were found. Metronidazole-resistant strains (2%) were isolated
      only in the first period. The most active beta-lactam drugs were piperacillin and
      ceftizoxime (resistance rate 16%), followed by ticarcillin mezlocillin and
      azlocillin (25%) and cefotaxime, cefotetam, and cefmetazol (around 40%). All
      strains tested were resistant to ampicillin and 4% to ampicillin/sulbactam.
      Cefoxitin resistance increased from 10% in the first two periods to 21% in the
      third and that of clindamycin from 12% in 1982 to 29% in 1987 and 50% in 1995.

PMID- 18611729
TI  - Preparation, properties and the effects of amikacin, netilmicin and tobramycin in
      free and liposomal formulations on Gram-negative and Gram-positive bacteria.
AB  - The most common problems limiting the medical use of aminoglycosides have been
      the nephro- and oto-toxicities and the increasing bacterial resistance. It has
      been shown that encapsulation of drugs into liposomes enhances their efficacy
      while reducing their toxicities. The present in vitro study was designed to
      evaluate the antimicrobial activities of free and liposomal amikacin, netilmicin
      and tobramycin. We, therefore, encapsulated these drugs into liposomes prepared
      by sonication. The drug contained in liposomes was measured by enzyme multiplied
      immunoassay technique (EMIT) after lysis of the vesicles by 0.2% Triton X-100.
      The comparative encapsulation efficiency of the three antibiotic preparations was
      assessed. Aminoglycosides kinetic release from liposomes in presence of normal
      human sera was also studied in vitro over a 48 h period at 37 degrees C under 5%
      CO(2). The MICs of these encapsulated drugs to Pseudomonas aeruginosa,
      Xanthomonas maltophilia, Escherichia coli, Streptococcus faecalis and
      Staphylococcus aureus were determined and compared to those of respective free
      drugs using an agar dilution method. The amikacin and tobramycin encapsulation
      efficiencies were significantly (P </= 0.05) higher (5.36% +/- 0.17 and 5.06% +/-
      0.10) than those of netilmicin (3% +/- 0.18). However, in presence of sera,
      liposomal retention of netilmicin was significantly (P </= 0.05) lower (61.88 +/-
      0.14%) than that of amikacin (81.45 +/- 0.64%) and tobramycin (94.07 +/- 0.18%)
      after 1 h of incubation and then remained nearly constant over an 48 h period of
      the study. The MICs of liposomal netilmicin against all bacterial strains tested
      were reduced, compared to those of free netilmicin. However, liposomal amikacin
      and tobramycin MICs were nearly similar to those of free respective drugs.
      Overall, liposomal netilmicin appears to be a promising approach in the
      management of Gram-positive and Gram-negative bacterial infections and should be
      further evaluated in in vivo experiments.

PMID- 18611730
TI  - In vitro activity of piperacillin/tazobactam against isolates from patients
      enrolled in clinical trials.
AB  - The in vitro activity of piperacillin alone or titrated with a constant
      concentration of 4 mug/ml tazobactam was evaluated against 3962 baseline
      pathogens isolated from 1899 patients enrolled in 9 clinical trial studies in
      North America. Tazobactam increased susceptibility rates of piperacillin for
      Enterobacteriaceae from 81% to 96%, Staphylococcus (methicillin susceptible) spp.
      from 6% to 100%, Bacteroides fragilis group from 79% to >99% and Haemophilus from
      85% to 98%. The excellent activity of piperacillin against Pseudomonas,
      Streptococcus and Enterococcus was maintained in the presence of tazobactam.
      Overall piperacillin/tazobactam had better activity than ticarcillin/clavulanic
      acid, ceftazidime, and in general equaled the activity of imipenem. The excellent
      in vitro, extended-spectrum activity of piperacillin/tazobactam suggests its
      utility for various infections.

PMID- 18611731
TI  - Ciprofloxacin and imipenem alone or in combination in experimental aortic valve
      endocarditis due to a ciprofloxacin borderline susceptible strain of Pseudomonas
      aeruginosa.
AB  - The in vivo efficacies of ciprofloxacin, imipenem and their combination were
      studied in the rabbit left-sided endocarditis model by using a seroresistant
      strain of Pseudomonas aeruginosa with borderline susceptibilities to
      ciprofloxacin (MIC/MBC 1 2 and 2 8 mug/ml to ciprofloxacin and imipenem,
      respectively). Both antimicrobials expressed synergy in vitro at the MBC level.
      Ciprofloxacin was given intramuscularly, 20 mg/kg of body weight q 8 h and
      imipenem at the same regimen intravenously for 9 days. When compared to the
      controls no significant differences were observed among the applied regimens
      regarding (1) blood culture sterilization, (2) percent of sterile vegetation, and
      (3) mean bacterial titers in vegetations. No strain isolated from vegetations at
      the end of therapy had developed resistance to either ciprofloxacin or imipenem.
      It is concluded that further studies are required after appropriate increase of
      ciprofloxacin dosage and more frequent administration and/or even higher doses of
      imipenem.

PMID- 18611732
TI  - Antimicrobial susceptibility patterns amongst group B streptococci from women in
      Harare, Zimbabwe.
AB  - As part of a larger study of vaginal pathogens in women in Harare, we have
      examined the antimicrobial susceptibility patterns of 130 isolates of group B
      streptococci (GBS). These organisms are important because of their association
      with preterm labour, premature rupture of membranes and neonatal sepsis. All of
      the isolates in Harare were fully sensitive to beta-lactams, with an MIC(90) for
      ampicillin of 0.38 mg/l, but five isolates were resistant in vitro to
      erythromycin, and each of these had an MIC >4 mg/l. Seven isolates showed
      resistance to clindamycin. Some isolates showed an intermediate sensitivity to
      gentamicin, but the great majority were resistant to this antibiotic. Studies in
      developed countries have shown that an intervention strategy, using intrapartum
      chemoprophylaxis, is effective in reducing the incidence of complications of GBS
      colonization in pregnant women. Our data suggest that ampicillin would be a
      suitable antibiotic for use in an intervention programme of intrapartum
      chemoprophylaxis in Harare.

PMID- 18611733
TI  - Different patterns of cytokine regulation of phagocytosis and bacterial killing
      by human neutrophils.
AB  - We describe here the capacity of human recombinant interleukin-1-beta (IL-1beta),
      interferon-gamma (INF-gamma), interferon-alpha (INF-alpha), tumor necrosis factor
      alpha (INF-alpha), interleukin-6 (IL-6) and interleukin-2 (IL-2) to modulate
      phagocytosis and bacterial killing by human neutrophils. IL-1beta, INF-gamma and
      TNF-alpha enhance phagocytosis of bacteria but do not have consistent effect on
      bacterial killing. In contrast, IL-6 augments bacterial killing but not
      phagocytosis of bacteria by neutrophils. INF-alpha augments and IL-2 depresses
      both antibacterial reactions of neutrophils. A direct effect of TNF-alpha
      (inhibition) and IL-2 (promotion) upon bacterial growth has been observed. It is
      concluded that (a) phagocytosis and intracellular bacterial killing are
      independent reactions of neutrophil-mediated antibacterial defence on the basis
      of different patterns of up- and down-regulation by cytokines, and (b) cytokines
      can exhibit direct effects on bacterial growth.

PMID- 18611734
TI  - Safety and tolerability of zalcitabine (ddC) in patients with AIDS or advanced
      AIDS-related complex in the European expanded access programme.
AB  - This international expanded access programme was initiated to provide zalcitabine
      (o 75 mg three times daily) to patients with AIDS or advanced ARC who had failed,
      were no longer able to tolerate or were ineligible to receive zidovudine (ZDV).
      Data are available from 517 patients. No unexpected adverse events occurred
      during the study with 13.2% of patients discontinuing treatment due to drug
      related adverse events. Peripheral neuropathy (PN) was the most common adverse
      event reported. This was considered to be at least possibly related to
      zalcitabine in 12.2% of patients, with only 2.3% of patients withdrawing from the
      study due to zalcitabine-associated PN. Patients with a baseline diagnosis of
      AIDS and a CD4 count </= 50 cells/mm(3) were most likely to develop PN on
      zalcitabine. Fifty-seven patients (11%) died during the study, with death
      considered to be at least remotely related to therapy in only 2 cases (1 case
      each of pancreatitis and cerebral toxoplasmosis with possible
      sepsis/granulocytopenia).

PMID- 18611735
TI  - Treatment of bone and joint infection with teicoplanin: a retrospective analysis
      of 50 cases.
AB  - The effectiveness and safety of teicoplanin, 400 mg/day, in combination with
      other antibiotics in the treatment of bone and joint infections was examined in a
      retrospective review of 50 cases (most commonly sepsis, osteitis and septic
      arthritis) treated at one hospital between 1988 and 1994. Previous antibiotic
      treatment had failed in 36 cases. Patients received teicoplanin and 1-3
      concurrent antibiotics for 4-141 days; 35 patients then received further
      antibiotics. Clinical success was recorded in 46 cases, with two failures and two
      non-evaluable outcomes. Bacteriological eradication was achieved in 43 cases.
      There was one recurrence at 8 months, which was successfully treated with
      teicoplanin. Five patients showed adverse reactions, but discontinuation of
      teicoplanin treatment was not necessary.

PMID- 18611736
TI  - Susceptibility surveillance of U.S. respiratory pathogen isolates to newer
      macrolide and azalide antibiotics.
AB  - Azithromycin and clarithromycin are both highly active in vitro against Gram
      positive respiratory pathogens, but azithromycin is substantially more potent
      against Haemophilus influenzae. We investigated the susceptibility of H.
      influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and S. pyogenes to
      azithromycin and clarithromycin, and determined the prevalence of beta-lactamase
      production in H. influenzae and M. catarrhalis. Results from three geographic
      regions of the USA were compared. A significantly greater proportion of H.
      influenzae isolates were susceptible to azithromycin than to clarithromycin
      (95.7% vs 63.1%, P < 0.001). M. catarrhalis, S. pneumoniae and S. pyogenes were
      highly susceptible to both antibiotics with no significant differences in
      susceptibility. beta-Lactamase was produced by 94.8% of M. catarrhalis isolates
      and 35.6% of H. influenzae.

PMID- 18611737
TI  - Transferable antibiotic resistance in Escherichia coli isolated from healthy
      Nigerian school children.
AB  - Three hundred and ninety-six E. coli isolates obtained from apparently healthy
      school children in Ile-Ife, Nigeria, were tested for their susceptibility to 11
      different antibiotics. Of these, only gentamicin, cefotaxime and nalidixic acid
      were found to have significant in vitro activity against most of the isolates.
      The incidence of antibiotic resistances encountered varied between 24% for
      trimethoprim and 55.5% for the sulphonamide. It was further observed that 47.5%
      of the isolates were identified as being multiply resistant, since they were
      simultaneously resistant to at least three different antibiotics. The 86
      trimethoprim-resistant isolates tested were found to be able to transfer this
      resistance trait together with resistance genes of to other antibiotics, into a
      plamidless strain of E. coli by conjugation. Seventy-seven of the trimethoprim
      resistant isolates were also found to be classifiable into the types of
      dihydrofolate reductases responsible for the observed resistance on the basis of
      hybridization experiments. The results of this study indicate that there is a
      large reservoir of antibiotic resistances within the community, and that the
      resistance genes were easily transferable to other strains even without direct
      exposure to antibiotics.

PMID- 18611738
TI  - Serotyping clinical isolates of Pseudomonas aeruginosa in relation to infection
      site antibiotic susceptibility and beta-lactamase production.
AB  - The present study investigates the association of O-serotype with isolation site,
      antibiotic resistance, and beta-lactamase production to determine the profiles of
      Pseudomonas aeruginosa clinical isolates circulating in a Canadian teaching
      hospital. The most frequently encountered serotypes of Pseudomonas aeruginosa
      strains isolated from inpatients at Hotel-Dieu de Montreal hospital during the
      period 1992-1993 were O1, O3, O5, O6, O10, and O11 (9-13%) isolated from pus,
      urine, sputa and other sources. Serotype O1 was the most sensitive in contrast to
      serotype O3 which was resistant to virtually all antibiotics tested except to
      imipenem and quinolone. Of the strains of Pseudomonas aeruginosa, more than 50%
      with the most encountered serotype produced a high level of beta-lactamase.

PMID- 18611739
TI  - Comparison of flomoxef with latamoxef in the treatment of sepsis and/or Gram
      negative bacteremia in adult patients.
AB  - The safety and efficacy of flomoxef and latamoxef were compared in the treatment
      of hospitalized patients with sepsis and/or Gram-negative bacteremia in a
      prospective, open-labelled clinical trial. Patients were randomized to receive 1
      to 2 g intravenous doses of either flomoxef every 6 to 12 h, or latamoxef every 8
      to 12 h. Data from 21 patients given flomoxef and 23 patients given latamoxef
      were included in the evaluation of efficacy. Flomoxef produced clinical cure and
      satisfactory microbiological responses in 85.7% and 100% of patients,
      respectively. These results were similar to those obtained with latamoxef (87%
      and 100%, respectively). In addition, no significant difference was found in mean
      age, sex, severity of infection, distribution of pathogens and focus of infection
      between the two groups. However, the flomoxef group included more patients with
      ultimately fatal diseases. Six patients given flomoxef and two patients given
      latamoxef developed superinfections caused by yeast, enterococci and Pseudomonas
      aeruginosa in the urinary tract. Mild and reversible adverse reactions probably
      related to flomoxef and latamoxef were noted in 14.3% and 13% of patients,
      respectively. The results of this study demonstrated that flomoxef is a safe and
      effective antimicrobial agent in the treatment of patients with sepsis and/or
      Gram-negative bacteremia.

PMID- 18611740
TI  - Subinhibitory concentrations of beta-lactams and other cell-wall antibiotics
      inhibit listeriolysin production by Listeria monocytogenes.
AB  - In the present study we tested the ability of beta-lactam antibiotics and other
      cell-wall antibiotics to inhibit the production of listeriolysin which is the
      main virulence factor of L. monocytogenes. The amount of listeriolysin produced
      was measured in the supernatants with a sensitive hemolysin assay and as beta
      galactosidase expression from the listeriolysin promoter. When tested in
      concentrations that did not affect growth of the bacteria, all beta-lactam
      antibiotics and all other cell-wall antibiotics tested were able to reduce the
      listeriolysin production in at least one of the tests used. Yet, no change in
      beta-galactosidase activity was detected in a strain harboring a control beta
      galactosidase fusion. We therefore demonstrate for the first time that
      subinhibitory concentrations of antibiotics specifically reduce the production of
      a virulence factor of L. monocytogenes.

PMID- 18611741
TI  - Cefoperazone/sulbactam versus cefoperazone plus mezlocillin: empiric therapy for
      febrile, neutropenic bone marrow transplant patients.
AB  - We conducted a prospective, randomized trial in 132 patients undergoing bone
      marrow transplantation comparing cefoperazone in combination with sulbactam (S),
      N = 66, vs. cefoperazone plus mezlocillin (CM), N = 66, as empiric antibiotic
      therapy for fever and neutropenia. Overall duration of neutropenia was 3-55
      (median, 13) days. Forty-one patients had positive initial cultures (S = 22 and
      CM = 19). Twelve of these 41 patients responded to initial study antibacterial
      agent treatment (S = 6 and CM = 6). Twenty-nine of 41 patients were withdrawn
      from study because of clinical deterioration, continued fever, or persistently
      positive cultures (S = 16 and CM = 13). Of the 90 patients who had culture
      negative fever (S = 44 and CM = 46), 44 subjects responded with or without the
      addition of amphotericin B (S = 21 and CM = 23). Thirty-seven of 90 patients were
      withdrawn from study due to continued fever or clinical deterioration (S = 17 and
      CM = 20). Nine patients were withdrawn as a result of rash or diarrhea (S = 6 and
      CM = 3). We conclude that in patients undergoing bone marrow transplantation,
      there was no difference in efficacy between cefoperazone/sulbactam and the
      combination of cefoperazone plus mezlocillin in the empiric treatment of the
      febrile neutropenic patient. Since the majority of initial infections were due to
      gram positive bacteria, consideration should be given to broadening initial
      empiric antibacterial agent therapy with drugs that possess potent activity
      against these organisms.

PMID- 18611742
TI  - Changes in susceptibilities to teicoplanin, vancomycin and other antibiotics
      among Staphylococcus aureus isolates in a tertiary-care University hospital.
AB  - Changes in antibiotics susceptibilities were evaluated among 374 nosocomial
      clinical isolates of Staphylococcus aureus collected from 1986 to 1994 in a
      tertiary-care University hospital where methicillin-resistant S. aureus (MRSA) is
      an increasing cause of infection. Significant increases in resistance to
      ciprofloxacin, clindamycin and rifampicin were observed among MRSA isolates in
      recent years. No resistance to glycopeptides was observed. However, during the
      last 2 years a significant trend towards a decreasing susceptibility to
      teicoplanin was observed among MRSA isolates.

PMID- 18611743
TI  - A microbiological assessment of silver fusidate, a novel topical antimicrobial
      agent.
AB  - The silver salt of fusidic acid is a novel antimicrobial agent. Against
      staphylococci, in vitro tests showed silver fusidate was more active than silver
      sulphadiazine, and the activities of the sodium and the silver salts of fusidic
      acid were correlated. Against streptococci, enterococci, clostridia, Candida
      albicans and a range of Gram-negative bacilli, silver fusidate was of similar
      activity to silver sulphadiazine. Silver fusidate at 1 g/l was bactericidal
      against eight strains of staphylococci, irrespective of their susceptibility to
      sodium fusidate. Emergence of resistance to silver fusidate was rare.

PMID- 18611744
TI  - Polymicrobial bacteremia in cancer patients: analysis of risk factors, etiology
      and outcome in 214 episodes.
AB  - Two hundred and fourteen episodes of polymicrobial bacteremia in 182 cancer
      patients in a period of 6 years in a 360-bed National Cancer Institute were
      analyzed for etiology, risk factors and outcome. Variables were compared with 187
      episodes of monomicrobial bacteremias in 147 cancer patients to find statistical
      significance among risk factors, etiology and outcome. Urinary catheters and
      breakthrough bacteremia were the only risk factors associated with polymicrobial
      in comparison to monomicrobial bacteremia (P < 0.05). Concerning etiology,
      Enterococcus faecalis, Candida spp., Acinetobacter calcoaceticus and
      Stenotrophomonas maltophilia were more commonly isolated in polymicrobial than in
      monomicrobial bacteremic episodes. Polymicrobial bacteremia presented more
      frequently with septic shock (22.9% vs. 9.0%, P < 0.05) and/or organ
      complications (25.2% vs. 11.8%, P < 0.05). However, mortality due to bacteremia
      did not significantly differ between polymicrobial and monomicrobial, but when
      polymicrobial bacteremia with and without coagulase negative staphylococci were
      compared, mortality in polymicrobial bacteremia without staphylococci was higher
      (10% vs. 4.7%, P < 0.04).

PMID- 18611745
TI  - In vitro activity of ampicillin, cefoperazone, their combinations with sulbactam
      and other antimicrobials: survey of Russian isolates.
AB  - Methodological differences makes it difficult to compare results of antimicrobial
      susceptibility testing obtained in Russia and in other regions. During the period
      from October 1993 to May 1994 susceptibility of 1296 isolates of bacteria was
      investigated according to NCCLS standards by the broth microdilution method. The
      order of activity of antibiotics against Gram-negative bacteria based on percent
      of susceptible strains from common hospitals were: amikacin (98%) > ciprofloxacin
      (93%) = imipenem (93%) > cefoperazone/sulbactam (92%) > ceftazidime (89%) >
      ceftriaxone (81%) > cefotaxime (80%) > cefoperazone (77%) > gentamicin (71%) >
      ampicillin/sulbactam (51%) > cefazoline (45%) > ampicillin (25%). The order of
      activity against strains from teaching hospitals was similar but the percent of
      susceptible strains was 10-20% less for the majority of antibiotics. The
      susceptibility level of Gram-negative isolates from Moscow teaching hospitals is
      lower than from Northern America and Europe. Ampicillln/sulbactam and
      cefoperazone/sulbactam, as well as other cephalosporins, demonstrated high
      activity against methicillin-susceptible staphylococci and penicillin-susceptible
      pneumococci. B-lactams/beta-lactamase inhibitor combinations were active against
      100% strains of anaerobic bacteria.

PMID- 18611746
TI  - Famciclovir, from the bench to the patient--a comprehensive review of preclinical
      data.
AB  - Famciclovir is converted rapidly and efficiently after oral administration to the
      selective antiviral compound, penciclovir. In cell culture, penciclovir is a
      potent inhibitor of herpes simplex virus (HSV) types 1 and 2, varicella-zoster
      virus (VZV), Epstein-Barr virus (EBV) and hepatitis B virus (HBV).
      Phosphorylation of penciclovir and aciclovir in uninfected cells is limited, and
      penciclovir, like aciclovir, has minimal effect on replicating cells in culture
      as expected for a selective antiviral agent. Mode of action studies with VZV and
      HSV have shown that the phosphorylation of penciclovir in infected cells is far
      more efficient than for aciclovir. This compensates for differences observed
      between penciclovir triphosphate and aciclovir triphosphate in the inhibition of
      HSV and VZV DNA polymerases. Because HBV is not known to encode a thymidine
      kinase, a different rationale for the selective inhibition of this virus by
      penciclovir is required. Recent data indicate that the DNA polymerase of HBV is
      far more sensitive to inhibition by penciclovir triphosphate than cellular DNA
      polymerases, suggesting that for this virus, selectivity operates at the DNA
      polymerase. Penciclovir triphosphate is more stable within infected cells than
      aciclovir triphosphate, and consequently penciclovir has more prolonged antiviral
      activity than aciclovir. Similarly, famciclovir is more effective than aciclovir
      or valaciclovir in suppressing HSV replication when given at a lower dosing
      frequency in certain animal models. These preclinical properties have helped to
      provide the foundation for the famciclovir clinical programme.

PMID- 18611747
TI  - Two rapid complementary methods to detect progressive zidovudine resistance
      mutations in mononuclear cells of HIV-infected patients.
AB  - The objective of the study was to evaluate a rapid screening technique for the
      presence of mutations in the viral reverse transcriptase gene of HIV following
      prolonged therapy with zidovudine in patients with AIDS. Peripheral blood
      mononuclear cells (PBMCs) of 14 HIV-infected patients were analyzed by micro
      titer point mutation assay (PMA) before therapy with zidovudine and after at
      least 10 months of treatment. In addition, five of these were analyzed
      longitudinally. Three nontreated HIV-seropositive individuals were tested as
      controls. To confirm the validity of the PMA, patients' material was also
      analyzed with the single strand conformational polymorphism (SSCP) assay. After
      10-55 months of treatment, at codons 41, 70, and 215 a shift from predominantly
      wild type strains to a mixture of wild type and mutant strains (21%-100% mutant
      sequences) appeared in the majority of patients' PBMCs. At codons 67 and 219, the
      wild type strain persisted after therapy in all but 3 patients. Most mutations
      were detected by SSCP as well as by PMA, except for one mutation at codon 41 and
      one at codon 70. However, when the two mutations were both present, SSCP and PMA
      were both able to detect these mutations. In conclusion, both PMA and SSCP are
      rapid and simple methods for screening for mutations causing drug resistance in
      zidovudine-treated HIV-infected patients. Although PMA is more labor-extensive
      than SSCP, the advantage of PMA over SSCP is that it permits the quantitative
      detection of point mutations coding for zidovudine resistance. The application of
      these assays may improve procedures of monitoring and modifying antiretroviral
      therapy on an individual basis.

PMID- 18611748
TI  - Treatment of diabetic foot infection: an open randomised comparison of
      imipenem/cilastatin and piperacillin/clindamycin combination therapy.
AB  - OBJECTIVE: To compare the clinical outcome and bacteriological response in
      diabetic patients with a foot infection treated with imipenem/cilastatin or a
      combination of piperacillin/clindamycin. METHODS: Patients hospitalised for
      diabetic foot lesions Wagner Stages II, III or IV were randomly assigned to
      receive either imipenem/cilastatin 500 mg QID or piperacillin 3000 mg QID in
      combination with clindamycin 600 mg TID. Cultures were obtained and clinical
      observations were made. RESULTS: Forty-six patients (mean age 71.4 +/- 9.8 years)
      entered the study, 22 received imipenem/cilastatin (IC) and 24 received
      piperacillin/clindamycin (PCL) combination therapy. In the IC group 22.2% was
      considered to be clinically cured, 76.2% improved. In the PCL group this was
      25.0% and 50.0%, respectively. In the IC treatment group 45.0% of baseline
      pathogens was eradicated compared to 70.0% in the PCL group. Adverse events were
      more often reported in PCL treated patients (50.0% vs. 19.0% P < 0.05).
      CONCLUSIONS: Impipenem/cilastatin and piperacillin/clindamycin combination
      therapy were equally effective in the treatment of patients with diabetic foot
      lesions. The imipenem/cilastatin regimen caused less side effects.

PMID- 18611749
TI  - Hepatosplenic candidiasis in non-neutropenic patients: a case report and
      literature survey.
AB  - Hepatosplenic candidiasis is an increasingly recognized infectious complication
      in patients who have an underlying malignancy and/or have chemotherapy-induced
      neutropenia. Only six cases of hepatosplenic candidiasis in non-neutropenic
      patients have been described to date, to which we add a seventh. Our patient had
      many of the classically described manifestations of hepatosplenic candidiasis,
      and responded well to therapy with amphotericin B. Retrospective comparative
      analysis of cases of hepatosplenic candidiasis reveals that non-neutropenic
      patients seem to respond well to medical therapy that is less intensive than that
      given to neutropenic subjects (total dosage of amphotericin B 0.84 g vs. 2.70 g,
      respectively) and tend to have a better prognosis (mortality rate 33% vs. 44%,
      respectively).

PMID- 18611750
TI  - Antibiotic resistance in nosocomial isolates in Scotland.
AB  - In this first multi-centre study in Scotland, 1028 consecutive Gram-negative and
      staphylococci strains were obtained from four major teaching hospitals. E. coli
      was the most common organism among both intensive care units (ICUs) (39%) and non
      ICU strains (46.6%). The prevalence of antibiotic resistance among E. coli was
      always higher in isolates from ICUs than non-ICUs: ceftazidime (14.1%, 7.2%),
      ceftriaxone (12.7%, 6.1%), cefotaxime (15.5%, 8.7%), cefuroxime (28.8%, 20.8%),
      amoxicillin plus clavulanic acid (52.2%, 38.8%) and gentamicin (7.0%, 2.8%). The
      highest incidences of resistance were identified among Enterobacter/Citrobacter
      spp. from ICUs; 43.8%, 41.7%, 45.8%, 54.2%, 87.5% and 10.4% of these organisms
      were resistant to ceftazidime, ceftriaxone, cefotaxime, cefuroxime, amoxicillin
      plus clavulanic acid and gentamicin, respectively.

PMID- 18611751
TI  - Emerging resistance in Salmonella enterica serotype Typhi in Hong Kong.
AB  - A total of 182 Salmonella enterica serotype Typhi isolated from three hospitals
      in Hong Kong from 1986 to 1992 were tested for their susceptibility to 21
      antimicrobial agents. Four percent or less were resistant to chloramphenicol,
      ampicillin, some of the cephalosporins, nalidixic acid, tetracycline and
      trimethoprim and 6% to 1024 mg/l sulfamethoxazole. All were susceptible to the
      aminoglycosides and the 4-quinolones. Nineteen isolates were resistant to at
      least 1, and up to 9, antibiotics. Of 8 chloramphenicolor multiply-resistant
      isolates studied, only 3 could transfer their resistances while resistance of one
      could only be mobilized. Four of 5 ampicillin-resistant strains produced a beta
      lactamase of pI 5.5. Antibiotic resistances were mediated by plasmids of 106, 116
      or 221 kb of incompatibility groups H, I1 and K. Three resistant isolates did not
      harbour any plasmid. A total of 43 (24%) S. Typhi harboured plasmids ranging in
      size from 4.3 to 221 kb. Plasmids of 106 kb and 8.5 kb were found in 17 and 10
      isolates, respectively. Restriction enzyme digestion of these two plasmids showed
      that each could be differentiated into 3 types. Of 89 isolates that were phage
      typed, 38% were untypable, while 17% and 12% were of phage types E1 and A,
      respectively, and the rest belonged to 17 other types.

PMID- 18611752
TI  - Comparative in vitro activity of nine antistaphylococcal agents against 275
      recent isolates of Gram-positive cocci.
AB  - The aim of this study was to compare the in vitro activities of 9
      antistaphylococcal agents including teicoplanin (TEI) against 275 non-repetitive
      clinical strains representing 15 species of staphylococci and 27 strains of
      Enterococcus (E.) faecalis, isolated from various specimens between 1991-1992 at
      a Canadian teaching hospital. The NCCLS agar dilution method was used (10(4)
      colonyforming units/spot). In terms of MIC(90), TEI and vancomycin (VAN) appeared
      to be the most potent antibiotics against all staphylococci tested (TEI: 2.0-4.0
      mug/ml; VAN: 1.0-2.0 mug/ml; ciprofloxacin (CPF): 0.25-32 mug/ml; cefazolin
      (CEF): 8.0-256 mug/ml; methicillin (MET): 2.0->256 mug/ml; imipenem (IMP): 1.0-32
      mug/ml; erythromycin (ERT): 16->256 mug/ml; ampicillin (AMP): 16-128 mug/ml;
      fusidic acid (FSA): 0.5-16 mug/ml). Multiple resistant strains, including MET
      resistant Staphylococcus (Staph.) aureus and Staph. epidermidis, were susceptible
      to TEI and VAN with respective MICs of 2-4 mug/ml and 1-2 mug/ml regardless of
      specimen type. Moreover, TEI was highly active against E. faecalis (MIC(90) for
      TEI and VAN: 0.5 and 4.0 mug/ml, respectively).

PMID- 18611753
TI  - In vivo TNF induction by culture supernatants of antibiotic-treated Escherichia
      coli 07:K1. Role of antibiotic class and concentration.
AB  - Antibiotics may cause an excess release of lipopolysaccharide (LPS) from bacteria
      and thereby promote the production of tumour necrosis factor (TNF). TNF was
      measured in the serum of Swiss mice challenged with filtered supernatant of
      Escherichia coli O7:K1 that had been exposed to various antibiotics in vitro.
      Expressed as a function of a standardized number of cells remaining after 6 h of
      exposure to gentamicin, ceftazidime, ciprofloxacin or imipenem, TNF leves
      associated with antibiotic exposure always exceeded those of controls. However,
      if differences in the remaining number of bacteria were not taken into account,
      TNF induction by supernatant of control untreated cultures was greater than that
      elicited by supernatant from any of the antibiotic-treated cultures. With the
      exception of imipenem, low-dose antibiotic exposure (0.5 x MIC) invariably
      induced higher TNF levels than did high-dose exposure (10 x MIC). Considerable
      antibiotic class- and concentration-related differences were noted. LAL
      equivalent amounts of LPS released by different antibiotics may diverge in their
      capacity to induce TNF. Our results do not support the notion that the use of
      rapidly bactericidal and lytic antibiotics should be avoided.

PMID- 18611754
TI  - Comparative antimicrobial activity and post-antibiotic effect of azithromycin,
      clarithromycin and roxithromycin against some respiratory pathogens.
AB  - Recent macrolide derivatives, roxithromycin, azithromycin and clarithromycin show
      more favourable pharmacokinetic characteristics in comparison to old ones and
      some differences in antibacterial activity. With the aim of improving our
      understanding of some aspects of their action against respiratory pathogens, we
      determined the MICs and MBCs of Streptococcus pneumoniae, Streptococcus pyogenes,
      Staphylococcus aureus, Moraxella catarrhalis and Haemophilus influenzae.
      Azithromycin was the most active agent against Haemophilus influenzae and
      Moraxella catarrhalis, while clarithromycin was more active against Streptococcus
      pneumoniae, Streptococcus pyogenes and Staphylococcus aureus with MICs similar to
      those of erythromycin. The bactericidal activity of all tested derivatives was
      weak against Staphylococcus aureus (MBC/MIC ratio approximately 16) and against
      Moraxella catarrhalis (MBC/MIC ratio, 8-16), but good against Staphylococcus
      pneumoniae, Streptococcus pyogenes and Haemophilus influenzae (MBC/MIC ratio, 2
      4). The determination of killing curves in the presence of 2 MIC and 10 MIC of
      azithromycin, clarithromycin and roxithromycin confirmed their weak bactericidal
      activity against Staphylococcus aureus and Moraxella catarrhalis as well as their
      effective activity against Streptococcus pyogenes and Streptococcus pneumoniae.
      Azithromycin showed the highest bactericidal activity against Haemophilus
      influenzae. As expected, the three derivatives produced a quite prolonged PAE
      when exposed to 5 MIC for 1 h, ranging between 2-4 h. The bactericidal activity
      and the prolonged PAE of new macrolides for the most common respiratory pathogens
      should assure a good clinical activity in respiratory infections including those
      sustained by Haemophilus influenzae, which is less susceptible to erythromycin
      and other old macrolides.

PMID- 18611755
TI  - Dapsone - the treatment of infectious and inflammatory diseases in dermatology.
AB  - Dapsone is known as useful in the treatment of infectious diseases. The use of
      the drug in infectious and inflammatory diseases in dermatology is reviewed.

PMID- 18611756
TI  - Perspectives for the chemotherapy of respiratory syncytial virus (RSV)
      infections.
AB  - Respiratory syncytial virus (RSV) is the major respiratory pathogen in infants
      and young children. Ribavirin is the only antiviral agent approved for the
      treatment of RSV infections, but its efficacy has remained controversial. In the
      past few years several compounds have been described that in vitro exhibit marked
      activity against RSV at a 50% effective concentration that is significantly
      lower, and with a selectivity index that is significantly higher, than that of
      ribavirin. Among the most potent and selective RSV inhibitors are various
      polyanionic substances (polysulfates, polysulfonates and polyoxometalates), EICAR
      (an IMP dehydrogenase inhibitor), pyrazofurin (an OMP decarboxylase inhibitor)
      and cyclopentenylcytosine (Ce-Cyd, a CTP synthetase inhibitor). These compounds
      should be further explored for their therapeutic potential in the treatment of
      RSV infections, following systemic or, preferably, topical administration (i.e.
      as an aerosol), as topical application may better mimic the potency and
      selectivity exhibited in vitro by these compounds.

PMID- 18611757
TI  - The emergence of resistance to amikacin in Serratia marcescens isolates from
      patients with nosocomial infection.
AB  - Administration of either amikacin (1985) or gentamicin (1984, 1986-1991) as first
      choice aminoglycoside did not decrease the high incidence of amikacin-resistant
      Serratia marcescens (ARSm) isolates responsible for nosocomial infections at the
      J.A. Fernandez Hospital of Buenos Aires (42% in 1984, 31% in 1985 and 41% in
      1987, differences not significant). In addition, a significant peak (P = 0.003)
      was detected in 1986, with an ARSm incidence of 70%. The incidence of ARSm
      decreased by 1988-1991 for reasons not related to aminoglycoside use. In the
      period 1984-1987 all S. marcescens isolates carried the 6'-aminoglycoside
      acetyltransferase-Ic [aac(6')-Ic] gene, while in addition 20% of the isolates
      contained the plasmid-encoded 3'-aminoglycoside-phosphotransferase-VIa[aph(3')
      VIa] and 2% the 6'-aminoglycoside-acetyltransferase-Ib [aac(6')-Ib] genes. From
      1988 to 1992 resistance to amikacin was associated with only 4 ARSm isolates and
      correlated with the appearance of Tn1331-related sequences in these isolates.
      This transposon or related sequences, however, was not widely spread in the S.
      marcescens population under investigation. Combined use of restriction fragment
      length polymorphism (RFLP), ribotyping and plasmid profile analysis revealed that
      S. marcescens strains of the same genotype, including isolates either expressing
      or not the aac(6')-Ic gene, were involved in outbreaks occurring in May 1984, May
      1985 and May 1986. Furthermore, these epidemiological tools permitted
      discrimination of different S. marcescens clones, each bearing a particular
      amikacin-resistance marker.

PMID- 18611758
TI  - Individualisation of HIV therapy based on HIV RNA load: the virologist's
      perspective.
AB  - There is increasing evidence that direct quantification of viral load by
      quantitative HIV RNA polymerase chain reaction (PCR) may be one of the more
      useful markers of disease status and antiviral treatment efficacy. Given the
      central role of viral replication in the pathogenesis of HIV infection, it is
      logical to assume that monitoring levels of cell-free virus in the plasma will be
      predictive of disease status. Furthermore, since the primary aim of treatment
      with current antiretroviral therapies is reduction of viral load, changes in
      plasma viraemia may be expected to be predictive of treatment effects.
      Preliminary data indeed suggest that viral load, is a useful marker of baseline
      prognosis, disease status and the effectiveness of antiretroviral therapy in
      individual patients. These data support the concept that measurement of viral RNA
      may eventually be of clinical utility in managing therapy of individual patients.
      However, prospective viral load studies are required to validate such a strategy.

PMID- 18611759
TI  - In vitro antifungal susceptibilities of Candida species isolated from the blood.
AB  - In vitro susceptibility of 158 strains of Candida species isolated from blood
      cultures to amphotericin B, flucytosine and fluconazole was evaluated. The broth
      macrodilution reference method of the National Committee for Clinical Laboratory
      Standards (NCCLS, M27-P) was adapted to the microdilution method. For 43 tests of
      standard strains, there were excellent agreement (within one doubling dilution)
      of minimum inhibitory concentrations (MICs) of amphotericin B and flucytosine
      with macrodilution reference. For fluconazole, 100% agreement was found using
      MICs scored 2 (prominent decrease in turbidity; MIC-2s) at 24 h reading, and much
      lower agreement using MICs scored 1 or at 48 h reading. In testing of the
      clinical isolates, amphotericin B and flucytosine demonstrated a very narrow
      range of MICs. On the other hand, fluconazole MICs showed a broad range and
      shifted substantially from higher level to lower level when MIC endpoints changed
      from the most strict MICs (complete absence of growth, MIC-0s) to a less
      stringent MIC-2s. However, MIC-2s distinguished C. glabrata as resistant compared
      with the other species. Also, MICs increased after prolonged incubation,
      particularly for fluconazole. Almost all Candida blood culture isolates tested
      were very susceptible to flucytosine. However, higher prevalence of fluconazole
      resistance was noted in our blood culture isolates than those in previous
      studies. The present study validated that broth microdilution method is an
      adequate tool for antifungal susceptibility testing following the recommendations
      provided by the NCCLS, and the MIC results might be determined as early as 24 h
      after incubation.

PMID- 18611760
TI  - Treatment of symptomatic amebic colitis in human immunodeficiency virus-infected
      persons.
AB  - While most Entamoeba histolytica appearing in male homosexuals infected with
      human immunodeficiency virus (HIV) is considered non-invasive in Western
      countries, and treatment of amebiasis in these persons has received very little
      attention, in Japan some male homosexual amebiasis patients infected with HIV
      complain of symptoms attributable to E. histolytica infection. We investigated
      whether symptomatic E histolytica amebic colitis in HIV-infected persons requires
      higher doses or longer duration of antiamebic drug therapy than in non HIV
      infected patients. Four symptomatic amebic colitis patients infected with HIV-1,
      three of them severely immunocompromised, with CD4 cell counts <200/mm(3), were
      treated with oral metronidazole: 1500 mg a day for 10 days in 2 patients, 1000 mg
      a day for 10 days in 1 patient, and 1000 mg a day for 6 days and then 750 mg for
      4 days in 1 patient, and good therapeutic results with no side effects were
      obtained. This indicates that symptomatic amebic colitis in HIV-infected persons
      can be successfully treated with metronidazole at the same dose and duration of
      treatment used in non-HIV-infected persons.

PMID- 18611761
TI  - Ultrastructural alterations in Trypanosoma (Schizotrypanum) cruzi induced by
      Delta(24(25)) sterol methyl transferase inhibitors and their combinations with
      ketoconazole.
AB  - We report the ultrastructural alterations induced on the proliferative stages of
      Trypanosoma cruzi, the causative agent of Chagas' disease, by two Delta(24(25))
      sterol methyl transferase (24(25)-SMT) inhibitors, 22,26-azasterol and 24(R,S),25
      epiminolanosterol. Both compounds are sterol biosynthesis inhibitors which had
      previously been shown to be potent growth inhibitors and whose effects are
      potentiated by the C14a demethylase inhibitor, ketoconazole. Epimastigotes
      treated with the minimal growth inhibitory concentration of 22,26-azasterol (10
      microM) for 144 h, which were completely depleted of endogenous 4-desmethyl
      sterols and accumulated 24-desalkyl sterols, showed the appearance of electron
      dense granules, mitochondrial swelling and intense vacuolization. At high
      concentration (> or = 30 microM) the sterol analog induced gross alterations in
      the organization of chromatin and rapid cell lysis. The treatment of
      epimastigotes with 24-(R,S),25-epiminolanosterol induced, at low concentrations,
      (1 microM) alterations similar to those observed with 22,26-azasterol but
      additionally, modifications of the kinetoplast were observed. Higher
      concentrations (> or = 3 microM) induced total lysis. The combination of both
      sterol analogs with ketoconazole, at sub-optimal concentrations, induced the same
      alterations as 22,26-azasterol 10 microM or epiminolanosterol 1 microM. The
      results confirm the conclusions of previous studies which indicated that one
      important cytotoxic effects of sterol biosynthesis inhibitors in this organism is
      the alteration of the parasite's mitochondrial system.

PMID- 18611762
TI  - High incidence of antifungal drug resistance in Candida tropicalis.
AB  - Drug resistance among yeasts is an increasing problem. Isolates of Candida krusei
      and Candida glabrata are recognized as having reduced susceptibility to
      fluconazole and resistance to this drug has also arisen in Candida albicans
      isolated from AIDS patients on long term azole therapy. Candida tropicalis (CT)
      is being increasingly isolated from human disease and is associated with invasive
      infection, however, data regarding this organism's drug susceptibility is
      limited. We report our findings on 60 isolates of CT isolated from patients with
      serious infection in the North West of England. Over 60% of isolates were from
      adult Intensive Care Unit (ICU) patients, and almost half were from the
      respiratory tract. Susceptibility to fluconazole, flucytosine, itraconazole and
      ketoconazole were tested by standardised methods - 48% of the isolates were
      resistant to fluconazole (MIC > 12.5 mg/l), and 10% had intermediate
      susceptibility (MIC 6.25-12.5 mg/l). For flucytosine 17% of isolates were
      resistant (MIC > 8 mg/l) and 22% had intermediate susceptibility (MIC 2-8 mg/l).
      Three isolates were resistant to both drugs. For itraconazole 17% of isolates
      were resistant (MIC > 1 mg/l), and 12% showed intermediate susceptibility (MIC
      0.5-1 mg/l). Resistance to ketoconazole was seen in 33% of isolates (MIC > 1
      mg/l) and 10% showed intermediate susceptibility (MIC 0.5-1 mg/l). Differences in
      the degree of cross resistance between the azole drugs was observed. Candida
      tropicalis should be added to the list of yeasts in which drug resistance is
      commonly found. Given the high invasiveness of Candida tropicalis, its affinity
      for patients on ICU and the high incidence of drug resistance in this species,
      identification and susceptibility tests should be performed on all yeast isolates
      from patients on ICU.

PMID- 18611763
TI  - Comparative anti-gonococcal activity of S-565, a new rifamycin.
AB  - The in vitro activity of S-565, a semi-synthetic rifamycin chemically related to
      rifampicin but with a longer half-life, has been compared with that of
      rifampicin, ciprofloxacin, spectinomycin, azithromycin and amoxycillin against
      Neisseria gonorrhoeae. Modal MICs against 20 strains were 0.13 mg/l for
      rifampicin and 0.5 mg/l for S-565. There was cross-resistance between the two
      rifamycins, and each selected for resistance at similar rates. In a time-kill
      study, S-565 was more rapidly bactericidal than rifampicin at x 1 and x 2 MIC.

PMID- 18611764
TI  - Pseudomonas aeruginosa biofilms are more susceptible to ciprofloxacin than to
      tobramycin.
AB  - The objective of this study was to determine and compare the biofilm elimination
      concentrations (BEC: the concentration which reduced the viability of biofilm
      organisms by at least 99.9%) of ciprofloxacin and tobramycin for Pseudomonas
      aeruginosa, a common cause of nosocomial biomaterial-related infections.
      Bacterial biofilms were produced in the modified. Robbins device using continuous
      culture flow at 60 ml/h for 40-44 h, and the sessile organisms were then exposed
      to either ciprofloxacin or tobramycin at a range of concentrations for 12 or 36h.
      The BEC of ciprofloxacin was 5 mug/ml for the 12 and 36 h treatments, a value 10
      x greater than the minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC). In contrast, the BEC of tobramycin was > 100
      mu/ml after 12h and 75 ug/ml following 36 h of drug exposure, that is 75-100 x
      the MIC and MBC. The results demonstrated that the BEC is a more suitable
      indicator of the antibiotic susceptibility of P. aeruginosa biofilms than the MIC
      and MBC. Ciprofloxacin was significantly more effective than tobramycin in the
      treatment of P. aeruginosa adherent to biomaterials. With respect to clinical
      application, if the intention of antibiotic use is to eradicate bacteria adherent
      to devices, only biofilm-active agents should be used.

PMID- 18611765
TI  - Kinetics of killing or growth of Trichomonas vaginalis in the presence of
      aminoglycosides, neomycin and geneticin (G418).
AB  - Few therapeutic drugs, other than metronidazole and close derivatives, are
      currently available to treat trichomoniasis. Trichomonas vaginalis is known to
      have a primitive ribosome based on small subunit ribosomal DNA sequence
      comparisons. Targeting ribosomal subunits, the aminoglycosides neomycin and
      geneticin (G418, distinct from gentamycin) were tested for activity against T.
      vaginalis. While neomycin had no effect, G418 was effective in killing cultured
      T. vaginalis cells at doses intermediate between those previously effective
      against prokaryotes and eukaryotes. G418 cytotoxicity requires further study
      before recommending this agent as topically applied therapy in refractory
      patients.

PMID- 18611766
TI  - Alarming drug-resistance rates for tuberculosis in Sureyyapasa Hospital, Turkey.
AB  - The susceptibility patterns to 'classic' tuberculous pleuritis can reflect the
      circulating strains in a society. The records of patients with 'classic'
      tuberculous pleuritis were reviewed retrospectively. Eighty-six patients were
      selected who were hospitalized between January 1990 and April 1994. Pleural fluid
      and tissue samples of patients were cultured in Lowenstein-Jensen medium. The
      isolated strains were subjected to drug susceptibility testing based on the
      absolute concentration method. We obtained 40 positive cultures in 86 patients
      with 'classic' tuberculous pleuritis. The resistance rate was 75% to one or more
      drugs, 27.5% to two drugs, 15% to three drugs, and 10% to four drugs. The
      resistance rates to isoniazid, rifampicin, streptomycin, and ethambutol were
      32.5, 55,42.5 and 32.5%, respectively. The resistance to isoniazid + rifampicin
      was 7.5%. Our findings indicate that the resistance rates for 'classic'
      tuberculous pleuritis are considerably high, reflecting the currently circulating
      resistance patterns in our region. The best regimen for new tuberculous cases and
      the appropriate regimens for drug-resistant cases should be designed and
      conducted by a nationwide institution.

PMID- 18611767
TI  - Antimicrobial susceptibility and serogroups of Salmonella isolates from Riyadh,
      Saudi Arabia.
AB  - The antimicrobial susceptibility and serogroups of 153 Salmonella strains
      isolated during a period of 22 months from both children and adults at a major
      teaching hospital in Riyadh, Saudi Arabia were studied. Antimicrobial
      susceptibility testing by comparative disc method and MIC determination by E-test
      method were performed on selected antimicrobial agents. For nalidixic acid and
      trimethoprim only the comparative disc method was used. Discrepancy between the
      two methods were noticed only in 1.3% of isolates. The majority of isolates from
      children (41%) were serogroup B, while those from adults (43%) were serogroup C1.
      The overall resistance was 16% to ampicillin and ampicillin/sulbactam, 13% to
      nalidixic acid, and 11% to chloramphenicol and trimethoprim/sulphamethoxazole.
      The resistance of Salmonella isolates to the so-called first line anti-Salmonella
      agents, i.e. ampicillin, chloramphenicol and trimethoprim/sulphamethoxazole, has
      increased compared to that reported 4 years ago from this Institution. Almost all
      isolates were susceptible to the second, and third generation cephalosporins,
      fluoroquinolones, aztreonam, mecillinam and gentamicin. Multiple drug resistance
      to two or more drugs was noticed in 16% of isolates, most of which were serogroup
      B. The majority of these multiple drug resistant isolates (96%) were ampicillin
      resistant and beta-lactamase producers. Although these isolates showed reduced
      MICs to ampicillin/sulbactam, their MICs were still higher than the
      susceptibility breakpoint for this combination. The nalidixic acid-resistant
      isolates showed higher MICs to the fluoroquinolones compared to the nalidixic
      acid-sensitive isolates. Isolates from children showed higher resistance to some
      of the antimicrobial agents compared to those from adults.

PMID- 18611768
TI  - Influence of ticlopidine on the development of experimental Staphylococcus aureus
      endocarditis.
AB  - Previously, we have shown that aspirin administration reduces the bacterial
      density and weight of aortic vegetations in a rabbit model of Staphylococcus
      aureus endocarditis. In the present paper, we sought to determine if ticlopidine,
      another potent inhibitor of platelet aggregation, also influences the development
      of endocarditis. Animals received either no ticlopidine (control), or oral doses
      of 10, 50, and 100 mg/kg daily. The 10 and 100 mg/kg treated groups had a
      statistically significant reduction of the vegetative weight as compared with the
      untreated controls. Although the 50 mg/kg dose did not result in a statistically
      significant difference (P = 0.058) in weight when compared with control, this
      dose also produced a substantial reduction in aortic value vegetation weights.
      None of the ticlopidine doses tested significantly altered the bacterial density
      relative to untreated controls. These findings suggest that ticlopidine alters
      the development of cardiac vegetations and may be useful agent for the prevention
      and/or treatment of infective endocarditis.

PMID- 18611769
TI  - Prophylaxis of cytomegalovirus infection in bone marrow transplant patients.

PMID- 18611771
TI  - Future directions on prophylaxis and therapy of cytomegalovirus diseases.

PMID- 18611770
TI  - Prevention of cytomegalovirus disease.
AB  - Cytomegalovirus (CMV) is the most important pathogen in the human herpes family
      for immunocompromised hosts. Recognition and monitoring of CMV disease has been
      improved due to development of four quantitative laboratory assays for CMV:
      antigenemia, polymerase chain reaction for CMV DNA, branched DNA assay, and the
      hybrid capture assay. Prevention of posttransplant CMV disease is possible with
      acyclovir or ganciclovir. Preemptive therapy, which is treatment begun when a
      laboratory marker signifies impending tissue-invasive CMV disease, offers a cost
      effective alternative to prophylaxis, but could be initiated too late in cases of
      fulminant CMV. Future strategies for control of CMV disease include determining
      the threshold quantity of CMV ('viral load') capable of producing tissue damage,
      developing drugs with a better therapeutic index than the presently available
      compounds, and insights into CMV pathogenesis especially regarding tissue tropism
      of the virus, which varies according to the underlying basic disease of the host.

PMID- 18611772
TI  - The first infection due to vancomycin-resistant Methicillin-resistant
      Staphylococcus aureus?

PMID- 18611773
TI  - Introduction.

PMID- 18611774
TI  - Clinical implications of aminopenicillins with beta-lactamase inhibitors.
AB  - Aminopenicillin/beta-lactamase inhibitor combinations (ampicillin/sulbactam and
      amoxicillin/clavulanic acid) are well established in the therapy of a wide range
      of infections in both hospital and primary-care settings as a result of their
      very broad-spectrum activity and good tolerability. These agents are particularly
      suited to the prophylaxis and treatment of polymicrobial infections. Clinical
      studies have demonstrated their efficacy in the treatment of diabetic foot
      infections, intra-abdominal infections, aspiration-related lung infections, brain
      abscesses and pelvic inflammatory disease, and in the prophylaxis of infections
      following abdominal, pelvic and head and neck surgery. Recent studies have also
      revealed that aminopenicillin/beta-lactamase inhibitors may provide therapy or
      prophylaxis which is more cost-effective than with comparative antimicrobial
      agents.

PMID- 18611775
TI  - Impact of beta-lactamases on the clinical use of beta-lactam antibiotics.
AB  - beta-Lactamase production is a very common mechanism of antibiotic resistance,
      occurring in a wide variety of important pathogens involved in both community
      acquired and nosocomial infections. The beta-lactamases can be divided into four
      classes (A, B, C, and D), each of which contains both chromosomal and plasmid
      encoded enzymes. The impact of beta-lactamases on the clinical use of beta-lactam
      antibiotics depends on the spectrum of activity of the enzymes, the prevalence of
      beta-lactamase production in a given species, the frequency of involvement of the
      pathogen in infections, and whether the infection is treated in hospital or in
      the community. The class A and class C beta-lactamases generally have the most
      impact on clinical practice. Plasmid-mediated class A enzymes are produced by a
      wide range of common pathogens; these enzymes are primarily penicillinases such
      as TEM(1), SHV(1) and ROB(1), but in addition include extended-spectrum beta
      lactamases which can also hydrolyze cephalosporins. The vast majority of the
      class A enzymes can be inhibited by currently-available beta-lactamase
      inhibitors. The class C enzymes or cephalosporinases, production of which is
      related to the presence of beta-lactam inducers, are present in nosocomial
      pathogens such as members of the Enterobacteriaceae, Pseudomonas aeruginosa and
      Acinetobacter spp. Constitutive hyperproduction of class C enzymes, resulting
      from mutations in regulatory genes, leads to third-generation cephalosporin
      resistance in these organisms. To provide the best antimicrobial treatment, and
      to ensure that beta-lactam antibiotics are used to their optimum effect,
      clinicians need to remain aware of the prevalence of particular beta-lactamases
      in their areas or institutions, and to make use of appropriate counter measures
      such as beta- lactam beta- lactamase inhibitor combinations.

PMID- 18611776
TI  - Clinical indications for beta-lactamase inhibitors in comparison to other
      antibiotics.
AB  - Combinations of beta-lactamase inhibitors and beta-lactam antibiotics have been
      used as a therapeutic strategy to overcome the growing problem of bacterial
      resistance. They have significant advantages over other existing antibiotic
      regimens and several such combinations have been developed for clinical use.
      Susceptibility studies have demonstrated the ability of sulbactam to extend the
      antibacterial activity of ampicillin to cover beta-lactamase-producing resistant
      strains. The clinical efficacy and safety of sulbactam/ampicillin has been
      emphasized by the results from a number of randomized trials, including studies
      in patients with community-acquired pneumonia, meningitis, endometritis and
      pelvic inflammatory disease, and diabetic foot infections. These studies have
      established the key role of sulbactam/ampicillin in the treatment of a wide
      variety of bacterial infections.

PMID- 18611777
TI  - Broad-spectrum beta-lactam antibiotics with beta-lactamase inhibitors.
AB  - Combining cefoperazone, piperacillin or ticarcillin with the beta-lactamase
      inhibitors sulbactam, tazobactam or clavulanic acid, respectively, results in
      compounds with activity against a wide range of Gram-positive and Gram-negative
      aerobic and anaerobic organisms, including strains producing beta-lactamases.
      Pharmacokinetics of the three combinations are similar. Cefoperazone/sulbactam
      can be given twice daily as opposed to a minimum of three-times-daily dosing
      required with the other combinations. All 9 combinations have a good safety
      profile, and may be administered parenterally for the treatment of severe
      infections in hospitalized patients, including intra-abdominal, gynaecological,
      skin and soft tissue infections. Additional cover may be provided by
      administering one of these combinations with an aminoglycoside.

PMID- 18611778
TI  - Ultrastructural alterations in Trypanosoma (Schizotrypanum) cruzi induced by
      Delta(24(25)) sterol methyl transferase inhibitors and their combinations with
      ketoconazole.
AB  - We report the ultrastructural alterations induced on the proliferative stages of
      Trypanosoma cruzi, the causative agent of Chagas' disease, by two Delta(24(25))
      sterol methyl transferase (24(25)-SMT) inhibitors, 22,26-azasterol and 24(R,S),25
      epiminolanosterol. Both compounds are sterol biosynthesis inhibitors which had
      previously been shown to be potent growth inhibitors and whose effects are
      potentiated by the C14a demethylase inhibitor, ketoconazole. Epimastigotes
      treated with the minimal growth inhibitory concentration of 22,26-azasterol (10
      microM) for 144 h, which were completely depleted of endogenous 4-desmethyl
      sterols and accumulated 24-desalkyl sterols, showed the appearance of electron
      dense granules, mitochondrial swelling and intense vacuolization. At high
      concentration (> or = 30 microM) the sterol analog induced gross alterations in
      the organization of chromatin and rapid cell lysis. The treatment of
      epimastigotes with 24-(R,S),25-epiminolanosterol induced at low concentrations (1
      microM) alterations similar to those observed with 22,26-azasterol but
      additionally modifications of the kinetoplast were observed. Higher
      concentrations (> or = 3 microM) induced total lysis. The combination of both
      sterol analogs with ketoconazole, at sub-optimal concentrations, induced the same
      alterations as 22,26-azasterol (10 microM) or epiminolanosterol (1 microM). The
      results confirm the conclusions of previous studies which indicated that one
      important cytotoxic effects of sterol biosynthesis inhibitors in this organism is
      the alteration of the parasite's mitochondrial system.

PMID- 18611779
TI  - Therapeutic effects of cefluprenam (CFLP) on polymicrobial infections associated
      with Enterococcus faecalis in rat pyometra model.
AB  - Enterococcus faecalis plays an important role as one of the pathogens in
      polymicrobial infections. We evaluated the efficacy of cefluprenam (CFLP) using a
      polymicrobial pyometra of a model rat. Rats were infected with a mixed
      intrauterine inoculation of E. faecalis plus either Bacteroides fragilis or
      Prevotella bivia (minimal inhibitory concentration of CFLP: E. faecalis, 3.13
      mug/ml; B. fragilis, 3.13 mug/ml; P. bivia, 3.13 mug/ml). Immediately after
      inoculating 10(5) cfu/rat of each organism, CFLP (either 40 mg/kg, i.v., q.i.d.
      for 5 days or 80 mg/kg, i.v., b.i.d. for 5 days) was administered. The
      intrauterine inflammatory change and bacterial count in the treated group were
      compared with those in the non-treated control group. CFLP significantly (P <
      0.01) decreased the bacterial counts except for B. fragilis in the regimen of 80
      mg/kg, b.i.d. However, the regimen of 40 mg/kg, q.i.d. significantly (P < 0.05)
      reduced the bacterial counts more than did that of 80 mg/kg, b.i.d. CFLP proved
      to demonstrate a good tissue concentration above 3 mug/g for 1 h. These results
      suggest that CFLP in a more divided dose is efficacious for the treatment of
      polymicrobial infections associated with E. faecalis in pyometra.

PMID- 18611780
TI  - Identification and mapping of new chromosomal sites affecting response to beta
      lactams in Staphylococcus aureus.
AB  - Seven new sites leading to increased beta-lactam susceptibility were identified
      and mapped in Staphylococcus aureus by Tn551 or Tn917 mediated insertional
      inactivation. Their effect was more pronounced in methicillin resistant than in
      susceptible strains. Except for inserts each in SmaI-K and SmaI-B, all were
      located on SmaI-A, which covers 25% of the staphylococcal chromosome. The
      physical position of the femAB operon involved in the expression of methicillin
      resistance was mapped on SmaI-A. Close to this site we identified a further site
      with almost as strong an effect on methicillin resistance as femAB. A second
      cluster of sites affecting methicillin resistance was identified at approximately
      30 kb from the femAB operon, showing that multiple unlinked factors may affect
      beta-lactam resistance. Interestingly, insert Omega2016 located in SmaI-B
      produced small colonies and was found to inactivate a gene of the electron
      transport chain, reminiscent of small colony variants observed in recurrent
      infections.

PMID- 18611781
TI  - Susceptibility of Pseudomonas aeruginosa to a photodynamic effect of the arginine
      hematoporphyrin derivative.
AB  - The photodynamic effect of the arginine hematoporphyrin derivative (HpD-Arg(2))
      on the growth of selected Pseudomonas aeruginosa clinical isolates is described
      as compared to the effect of hematoporphyrin derivative (HpD). Growth inhibition
      of HpD-Arg(2) of three Gram-positive strains (Staphylococcus aureus, Bacillus
      subtilis and Micrococcus luteus) and five laboratory strains of Gram-negative
      bacteria (Escherichia coli, Proteus vulgaris, P. aeruginosa, Klebsiella
      pneumoniae and Enterobacter cloacae) was observed as well. Serratia marcescens
      strain was resistant to light-activated HpD-Arg(2) or HpD. The antimicrobial
      activity of light-activated HpD-Arg(2) against P. aeruginosa may offer an
      additional option in the anti-pseudomonal therapy of wounds.

PMID- 18611782
TI  - Nosocomial Streptococcus pneumoniae infection causing children's acute otitis
      media.
AB  - Streptococcus pneumoniae is the most frequent pathogen in young children's acute
      otitis media. It also plays a significant role in nosocomial ear infection in
      children, while it causes pneumonia with or without bacteremia in hospitalized
      elderly people. Multiple antibiotic resistant strains are prevalent among S.
      pneumoniae isolates from the respiratory tract of hospitalized patients in
      Hungary. This fact makes therapeutic reconsiderations concerning the use of oral
      beta-lactams mandatory. In this retrospective study two nosocomial outbreaks
      caused by multiresistant S. pneumoniae in two pediatric hospitals are described.
      The patients admitted with a chronic underlying disease (milk intolerance and
      gastro-oesophageal reflux were predominant) or respiratory tract infection
      acquired acute otitis media. Therapy with oral beta-lactams (first and second
      generation cephalosporins and amoxicillin), macrolides and co-trimoxazole was
      ineffective in most of the cases or resulted in transient improvement. In some
      cases acute otitis media resolved with the improvement of the underlying
      condition, in two cases administration of cefotaxime resulted in recovery and in
      one case mastoidectomy became necessary.

PMID- 18611783
TI  - Klebsiella and extended spectrum beta-lactamases.
AB  - During the past 14 years a rapid, world-wide increase in prevalence of Klebsiella
      pneumoniae resistant to late generation cephalosporins has occurred. A growing
      number of newly identified plasmid encoded beta-lactam hydrolyzing enzymes has
      broadened the spectrum of primitive beta-lactamases allowing inactivation of a
      wide variety of beta-lactam agents. The extrachromosomal genes which code for
      these enzymes often exist with genes expressing resistance to several other
      classes of antibacterial agents, potentially arming Klebsiella pneumoniae with
      resistance to all therapeutically available antibiotics. More focused
      surveillance studies and individualized strategies within institutions are
      necessary to reduce this insidious trend.

PMID- 18611784
TI  - Penicillin-binding proteins. Wall peptidoglycan assembly and resistance to
      penicillin: facts, doubts and hopes.
AB  - The assembly of the bacterial cell wall peptidoglycan relies upon the
      availability of a ready-made precursor, the lipid II intermediate. This
      intermediate is taken up by a multifunctional factory that provides the required
      enzymatic activities for polymer assembly at the exterior of the plasma membrane.
      Morphogenetic networks regulate the synthesis in a cell-cycle-dependent fashion.
      As essential components of the cell machinery are targets of beta-lactam
      antibiotics, safety devices protect the cells against these toxic agents.
      Controversy and consensus formation lie at the heart of the scientific research.
      This review focuses on questions that bacterial cell wall biochemists still
      strive, with increasing success, to answer.

PMID- 18611785
TI  - Multidrug resistance in Mycobacterium tuberculosis.
AB  - All but one of the four major mechanisms of resistance to antimicrobial agents
      inactivation of the drug, altered cell wall permeability or drug efflux, drug
      titration due to target overproduction, and alteration of the target by mutation
      appear to be employed by Mycobacterium tuberculosis in its resistance to
      components of short course chemotherapy regimens. To date no enzymes capable of
      inactivating any of the frontline drugs have been found. The most common
      resistance mechanism is alteration of the target leading to inadequate drug
      binding, or drug activation, as a result of mutations in chromosomal genes. This
      occurs in the case of the specific antituberculous drugs isoniazid, pyrazinamide
      and ethionamide as well as in resistance to the broad-spectrum antibiotics,
      rifampicin, streptomycin and the fluoroquinolones. Overproduction of the drug
      target also appears to lead to resistance to isoniazid and ethionamide whereas
      changes in permeability, or the activation of antibiotic-efflux systems, may
      contribute to the low-level resistance of the tubercle bacillus to streptomycin
      and fluoroquinolones.

PMID- 18611786
TI  - Meropenem: evaluation of a new generation carbapenem.
AB  - Meropenem is a new beta-lactam antibiotic belonging to the carbapenem class. It
      differs structurally from imipenem, the first carbapenem to be marketed, by
      possessing a 1-beta-methyl group on the carbapenem moiety and a substituted 2'
      side chain. Meropenem is relatively stable to human dehydropeptidase-I (DHP-I),
      and therefore, unlike imipenem, it does not need to be administered with a DHP-I
      inhibitor such as cilastatin. Meropenem has an ultra-broad spectrum of
      antibacterial activity which encompasses Gram-positive and Gram-negative aerobes
      and anaerobes, including many strains resistant to other antibacterials. Compared
      to imipenem, meropenem is more active against Enterobacteriaceae and Pseudomonas
      aeruginosa and a little less active against some Gram-positive cocci. Meropenem
      is susceptible to few clinically important beta-lactamases. Meropenem exhibits a
      linear pharmacokinetic profile which shows predictable age and disease-related
      changes. Elimination is primarily renal with a half-life of approximately 1 h
      after intravenous (IV) administration. Meropenem monotherapy has proved
      efficacious in the treatment of a variety of infections in adults and children
      and can be administered by bolus IV injection, as well as IV infusion and
      intramuscular (IM) injection. Prospective, randomised clinical trials have shown
      it to be as efficacious as comparator regimens in the treatment of lower
      respiratory tract, intra-abdominal, urinary tract and skin and soft tissue
      infections, meningitis and septicaemia. Furthermore, meropenem monotherapy has
      demonstrated efficacy in the empirical treatment of febrile neutropenic cancer
      patients. Meropenem is well tolerated by the CNS in clinical studies, which
      reflects animal data, suggesting a low propensity to cause seizures. Thus,
      meropenem is an important new antibacterial which should prove particularly
      useful in severe and polymicrobial infections and those caused by organisms
      resistant to other agents.

PMID- 18611787
TI  - High dose parenteral ciprofloxacin in pleuro-pulmonary disease: a comparative
      pharmacolinetics of 400 and 200 mg intravenous.
AB  - In this study we determined the pharmacokinetics of higher IV doses of
      ciprofloxacin (Cipro) in patients with pleuro-pulmonary diseases undergoing
      treatment for various bacterial infections. Cipro IV was infused over 30-45 min
      in 11 patients (seven on 400 mg bid, four on 200 mg bid). Blood samples were
      taken at intervals of up to 4 h and assayed for Cipro using the HPLC method. The
      'mean' peak concentration (C(max)) was 6.9 +/- 2.2 (S.D.) and 11.8 +/- 5.2 (S.D.)
      for the 200 and 400 mg groups, respectively. The mean concentrations at 1.5 h
      were 1.2 and 2.6 mg/l and the area under the curve in 0-4 h was 4.6 +/- 0.9
      (S.D.) and 7.5 +/- 2.4 (S.D.), respectively for the 200 and 400 mg groups. Steady
      state serum concentrations of 400 mg were approximately double those for the 200
      mg group. IV 200 mg did not reach the required levels to cover the minimum
      inhibitory concentrations (MICs), whereas, 400 mg IV dose clearly will provide an
      improved coverage for the commonly encountered organisms with MICs in the 1-4
      mg/l range.

PMID- 18611788
TI  - Plasmid-encoded resistance to arsenic compounds in Gram-negative bacteria
      isolated from a hospital environment in Venezuela.
AB  - Resistance to arsenic compounds was examined among amikacin resistant Gram
      negative bacteria isolate from a hospital environment. Arsenite resistance
      (Ars(r)) was found in a high proportion of isolates ( >60%) being frequently
      associated with resistance to tellurite (40%), and to other antimicrobial agents.
      Ars determinants (27%) were found to be transferable to E. coli K12 strains from
      which large plasmid DNA molecules were isolated and characterized by agarose gel
      electrophoresis. Plasmids were identified by both classical incompatibility
      tests, and by replicon typing using DNA specific probes. Most of the amikacin
      arsenite (Ak-Ars) conjugative plasmids belong to the H incompatibility group.
      These results suggest that Ak-Ars resistance linked to IncH plasmids is wide
      spread in Gram-negative bacteria.

PMID- 18611789
TI  - Observations on oral Sultamicillin/Unasyn CP-45 899 therapy of neonatal
      infections.
AB  - The use of an effective antimicrobial remains a problem in the neonate, thereby
      necessitating empiric combinations of parenteral agents. We therefore studied
      oral Sultamicillin's (Unasyn CP-45 899) efficacy and tolerability (dose = 50
      mg/kg per day) in the treatment of serious infections in 27 neonates over an 18
      month period. The study cohort comprised newborns with suspected or confirmed
      infections in the Special Care Baby Unit of a referral hospital. The infants with
      overwhelming/severe infections or proven/suspected renal, hepatic or hematologic
      disease; or known hypersensitivity to penicillins or any beta-lactams were
      excluded. There were 12 babies with skin and soft-tissue infections, although
      pneumonia [11] was most predominant in our series. Bacterial isolates were mainly
      Staphylococcus aureus, Escherichia Coli and Klebsiella pneumoniae with a beta
      lactamase production rate of 88%. The clinical cure and improvement rates were
      96.3 and 100%, respectively and the evaluable bacteriologic cure-rate was 93.8%.
      The mean (S.D.) duration of therapy was 7.4 (2.6) days (range, 4-14) with
      significant resolution of features occurring within a 48 h period (24 27 , P <
      0.01). No serious adverse/side effects were seen as only one (3.7%) experienced
      mild loose stools. We show with these prospective observations (our cohort albeit
      small) that sultamicillin orally is efficacious, tolerable and safe for treating
      of mild to moderate infections in the newborn caused by both gram-positive and
      gram-negative pathogens.

PMID- 18611790
TI  - Increasing nosocomial infections of methicillin-resistant Staphylococcus aureus
      at a teaching hospital in Taiwan.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide important
      pathogen in nosocomial infections. To investigate the extent of the problem in
      Taiwan, analysis for the period of 1981-1994 was carried out of prospective
      surveillance data from the National Taiwan University Hospital, a major
      university teaching hospital in Taiwan. The number of nosocomial MRSA infections
      increased from five in 1981 to 133 in 1994, and the incidence increased from 0.2
      episodes/1000 discharges in 1981 to 2.9 episodes/1000 discharges in 1994. The
      most common infection site was surgical wounds, which accounted for 26.3% of
      total 577 episodes of nosocomial MRSA infections during the study period.
      However, bacteraemia has become more and more common during the past 14 years.
      MRSA infections occured more frequently in patients stayed in the burn unit and
      other intensive care units than in the general wards. Other than oxacillin, the
      resistance rate to many other antibiotics also increased in S. aureus strains
      causing nosocomial infections in this hospital. Vancomycin remained active to all
      these S. aureus strains, even until 1994.

PMID- 18611791
TI  - Survey of Bacteroides fragilis group susceptibility patterns in Brazil.
AB  - A total of 83 clinical isolates of the Bacteroides fragilis group collected from
      two Brazilian hospitals during 1993 and 1994, were tested for susceptibility to
      six antimicrobial agents by using an agar dilution method. The species most
      frequently isolated was B. fragilis (63.8%), followed by B. thetaiotaomicron
      (15.6%), B. vulgatus (9.6%) and B. distasonis (7.2%). The various species of the
      B. fragilis group had different patterns of resistance; B. fragilis was the most
      susceptible species in both medical centers. All isolates were susceptible to
      metronidazole and chloramphenicol. The following resistance rates were observed:
      89.1% (Penicillin G); 77.1% (tetracycline); 18% (clindamycin) and 7.2%
      (cefoxitin). These results reflect the value of identification of clinical
      important isolates and the periodic determination of B. fragilis group
      susceptibility patterns at each medical institution.

PMID- 18611792
TI  - Oxacillin susceptibility of coagulase-negative staphylococci: role for mecA
      genotyping and E-test susceptibility testing.
AB  - For 115 clinical isolates of coagulase-negative staphylococci which were acquired
      from 100 patients, we compared the results of routine critical agar dilution
      susceptibility testing (4% NaCl, 6 mg/ml oxacillin) with mecA gene detection by a
      polymerase chain reaction amplification. Discrepant results were subsequently
      reassessed with critical agar dilution testing, repeat mecA genotyping, disc
      radial diffusion susceptibility testing, E-test and determination of beta
      lactamase status. For the initial comparisons, 36 isolates were susceptible and
      lacked mecA whereas 54 isolates were resistant and had evidence of mecA. Among 17
      mecA positive/agar dilution susceptible bacteria, four were clearly resistant by
      E-test, one isolate had borderline resistance (MIC, 2-4 mg/l), and 12 were
      resistant when E-test was applied to resistant subpopulations. Initial E-tests
      facilitated the recognition of the heteroresistant isolates. For eight mecA
      negative/agar dilution resistant isolates, two were confirmed as oxacillin
      susceptible and six were mecA positive upon retesting. Although 53.9% had been
      classified initially as resistant by agar dilution, 67.0% were finally deemed
      resistant. Critical agar dilution underestimates oxacillin resistance among
      coagulase-negative staphylococci, and accurate detection of resistance is
      facilitated by mecA genotyping and E-test.

PMID- 18611793
TI  - Febrile neutropenia in a bone marrow transplantation unit.
AB  - In our clinic, between May 1988 and December 1994, 117 bone marrow transplants
      (78 allogenic BMT (alloBMT), 26 autologous BMT (autoBMT), 13 autologous
      peripheral stem cell transplant (autoPSCT). Eighty-six (73.5%) febrile
      neutropenic episodes (FNEs) were encountered (64 alloBMTs, 15 autoBMTs, 7
      autoPSCTs). There were 28 (32.5%) microbiologically documented infections, 18
      (20.9%) clinically documented infections and 40 (46.5%) FUO. Gram-positive
      microorganisms were the most frequently isolated agents (57.1%) and
      Staphylococcus spp. were the main pathogens to cause bacteremia (%54.1).
      Enterobacter spp. were the most common (75%) in urinary tract infections, FNEs
      were most frequently (82%, 64 78 ) encountered in AlloBMT patients. No
      significant difference in the number of FNEs was found between autoBMT and
      autoPSCT groups (P < 0.05). Overall response rate to empirical antibiotherapy was
      87.2% (75 86 ) and the success of treatment disclosed no difference in relation
      to transplant type and definition of infection (P > 0.05). Seven (6%) patients
      suffered from catheter infections and eight (7%) from Candida esophagitis.

PMID- 18611794
TI  - Induction of antibacterial activity by alpha-d-oligogalacturonides in Nephrolepis
      sp. (pteridophyta).
AB  - This paper presents data on the induction by alpha-d-oligogalacturonides (OG) of
      antibiotic activity in vitro by the fern Nephrolepis sp. The extracts from the
      fern grown aseptically, partly in a medium containing a mixture of OG and partly
      in a medium lacking OG, as control, were tested against several bacterial
      strains. The results show that the OG mixture promotes the production of
      antibiotic compounds. Comparing the present results with those on the
      antimicrobial properties of the same fern grown in a greenhouse, we discuss the
      hypothesis that the production of antibiotic substances can be elicited by
      different factors, such as products of synthesis or degradation of the biotic
      component of the soil or by OG (in axenic culture) that can mimic the effect of
      natural elicitors.

PMID- 18611795
TI  - Pharmacokinetics of three new beta-lactams in the Yucatan micropig model
      administered by intravenous bolus injection and continuous infusion.
AB  - The miniature pig is becoming a popular non-rodent animal model in biochemical
      research because of physiological similarities to humans. In addition, the
      micropig presents the advantages of large animal species for experimental
      pharmacokinetics. However, pharmacokinetics of antimicrobial agents are poorly
      documented in the pig and further work is needed to establish interspecies
      comparisons. This prompted us to investigate the disposition of three well
      documented beta-lactams (cefepime, cefpirome and meropenem) in this model and
      also to evaluate the potential to use it for pharmacodynamic studies. Each drug
      was given following a single dose both by direct intravenous injection (or short
      infusion for meropenem) and continuous infusion. Six animals were enrolled in
      each group. Blood samples were obtained over a 0-12 h period, using a catheter
      placed in the external jugular vein. All beta-lactams were assayed by high
      performance liquid chromatography (HPLC). Pharmacokinetics of cefepime and
      cefpirome given by bolus injection in the microswine were close to those in man
      receiving equivalent dosage (i.e. 2 g). The terminal half-lives are similar
      (human: 1.80 h, 1.80 h; pig: 1.46 h, 1.29 h) as is the case for clearance values
      (human: 1.82, 1.80; pig: 1.90, 1.74 ml/min per kg) for cefepime and cefpirome,
      respectively. The administration by continuous infusion does not influence the
      elimination rate of cefepime, cefpirome and meropenem. Meropenem kinetics in the
      micropig were also similar to those in man. The terminal half-lives are similar
      (human, 0.83 h; pig, 0.88 h) as in the case for clearance values (human, 4.0 h;
      pig, 4.90 ml/min per kg) after 30 min intravenous infusion of meropenem. We
      concluded that the micropig is an adequate model for the study of the
      pharmacokinetics and probably the pertinent model for ex-vivo pharmacodynamics
      investigations of cefepime, cefpirome and meropenem.

PMID- 18611796
TI  - Q fever--a review and issues for the next century.

PMID- 18611797
TI  - The effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in
      mice.
AB  - Five bisbenzylisoquinoline (BBI) alkaloids, curine, cycleanine, isotet:andrine,
      limacine and pheanthine were tested for trypanocidal activity in C 3H He mice
      infected with Y or CL strain of Trypanosoma cruzi. The activity was compared with
      the baseline drug, benznidazole. Oral treatment was more effective with curine at
      10 mg/kg or with cycleanine at 2 mg/kg daily for 10 days in mice infected with Y
      or CL strain. In these groups, the parasitemias were negative after 5-7 weeks
      after inoculation and mortality time 50 (MT(50)) was significantly higher than
      untreated mice. Benznidazole was effective in mice infected with CL strain but
      not in mice infected with Y strain. The other BBI showed a relative efficacy
      against both strains. The effect of BBI alkaloids could be due to a blocking of
      the Ca2+ channel for the regulation of T. cruzi infectivity to invade host cells
      or their selective immunosuppressive properties.

PMID- 18611798
TI  - Antimicrobial therapy of peptic ulcers.
AB  - It is now accepted that peptic ulcer disease, whether duodenal or gastric, is one
      manifestation of infection with the bacterium Helicobacter pylori. This
      realization has revolutionized the management of peptic ulcer disease and changed
      the dictum from no acid no ulcer, to no H. pylori, no ulcer. When confronted with
      a patient with peptic ulcer disease, the physician must now ask whether H. pylori
      infection is present and if so, attempt to cure it. The gastric milieu is a very
      difficult environment for effective antimicrobial therapy. Nevertheless, current
      multi-drug antimicrobial therapy can be expected to cure the infection in more
      than 80% of patients. Cure of the infection is associated with a very low rate of
      recurrence. The continued risk of serious disease or disease complications
      associated with treatment failure and the availability of the urea breath test to
      non-invasively assess the results of therapy suggest that post therapy assessment
      should be routine. Because H. pylori infection causes structural and functional
      damage to the stomach and is associated with a lifetime risk of peptic or gastric
      cancer of approximately 16 and 1%, respectively, the infection should be treated
      whenever it is diagnosed. This paper reviews the current approach to therapy of
      patients with H. pylori infection, the effective antimicrobial drug combinations
      end the factors that predict treatment failure. Emergence of antimicrobial
      resistance may soon undermine the effectiveness of current drug regimens and
      require pretreatment culture and sensitivity testing as well as development of
      new drugs and drug regimens.

PMID- 18611799
TI  - Microbial multidrug resistance.
AB  - Multiresistance plasmids and transposons, the integrons, the co-amplification of
      several resistance genes or finally the accumulation of independent mutations can
      lead to microorganisms resistant to multiple drugs. On the other hand multidrug
      resistance is due to an efflux pump conferring resistance to unrelated drugs.
      These microbial efflux pumps are belonging to various transporter families and
      are often encoded in microbial genomes. There is mounting evidence that these
      efflux systems are responsible for clinical multidrug resistance in bacteria,
      yeasts and parasites.

PMID- 18611800
TI  - Recombinant human erythropoietin for treatment of anemia in persons with AIDS not
      receiving zidovudine.
AB  - Because few data exist on the effect of recombinant human erythropoietin (EPO)
      for anemia not induced by zidovudine (ZDV) in persons with AIDS, we analyzed a
      subset of 523 subjects not taking ZDV ('non-ZDV') who participated in an open
      label EPO treatment program involving 1943 subjects. Non-ZDV subjects had a mean
      hematocrit of 27.3% on entry and their mean weekly EPO dose was 354-464 U/kg that
      was given for a mean of 17 weeks. EPO was well tolerated with an adverse event
      discontinuation rate of 2.3%. The mean hematocrit increased to 30.8% at week 6
      and remained between 32 and 34% for the next 18 weeks. Subjects requiring one or
      more transfusion per 6-week period decreased from 43% before study entry to 14%
      for weeks 13-18 and 18% for weeks 19-24. These changes were comparable to those
      observed in the entire group of 1943 patients. We concluded that EPO was safe and
      as effective for anemia in persons with AIDS not taking ZDV as for those
      receiving it.

PMID- 18611801
TI  - In vitro comparative assessment of beta-lactamase inhibitors and their penicillin
      combinations against selected enterobacteria.
AB  - A comparative in vitro assessment of the inhibitory activity of clavulanate,
      sulbactam and tazobactam against the most frequent beta-lactamases found in
      enterobacteria isolated in Greek hospitals, has been performed. Tazobactam and
      clavulanate were potent inhibitors of TEM-1, SHV-1, SHV-2 and SHV-5 while
      sulbactam was less effective. In addition, tazobactam exerted a moderate
      inhibitory activity against AmpC-type beta-lactamases. In contrast with
      clavulanate, tazobactam could not cause significant induction of chromosomal
      cephalosporinases. Potentiation of the activity of penicillins (amoxycillin,
      ampicillin, ticarcillin and piperacillin), when combined with the inhibitors, has
      also been evaluated using a sample of recently isolated enterobacteria with beta
      lactamase-mediated resistance. The results showed that the most effective among
      the commercially available combinations, is piperacillin/tazobactam followed by
      ticarcillin/clavulanate.

PMID- 18611802
TI  - Antibacterial activity in Actinidia chinensis, Feijoa sellowiana and Aberia
      caffra.
AB  - The antibacterial activity of extracts from various parts of plants (leaves,
      fruits and stems) was studied in Actinidia chinensis, Feijoa sellowiana and
      Aberia caffra. These are tropical plants used for food. The fruits (subdivided
      into skin, pulp and seeds), leaves and stems were separately extracted and
      tested, in triplicate, against eight Gram positive and Gram negative bacterial
      strains. All the extracts, except from the leaves of A. caffra, showed activity
      against all the strains employed. Inhibition of bacterial growth was tested
      against Na-cefotaxime, benzyl penicillin and tetracycline. The antibiotic
      activity of fruit resides essentially in the seeds. The antibacterial activity of
      extracts from vegetative plant parts was generally less active that from fruit
      extracts. The minimum inhibiting concentration (MIC) and minimum bactericidal
      concentration (MBC) were determined for all the extracts and showed exclusively
      bacteriostatic activity.

PMID- 18611803
TI  - Mechanisms of resistance to piperacillin of Enterobacter cloacae strains differ
      by antibiotic prescription policy.
AB  - During a study of piperacillin resistance among aerobic Gram-negative bacteria,
      18 resistant strains of Enterobacter cloacae were obtained from a General
      Hospital in Rotterdam and 13 from a University Hospital in Amsterdam. The
      patterns of antibiotic susceptibilities were different: the Amsterdam strains
      were generally resistant to penicillins, the third generation cephalosporins and
      temocillin, whereas the Rotterdam strains were more often sensitive to the third
      generation cephalosporins and temocillin but more resistant to penicillins.
      Isoelectric focusing and substrate profiles showed the presence of chromosomal
      Class 1 beta-lactamase in ten of the Amsterdam strains: in three strains a
      plasmid mediated TEM-1 enzyme was detected. In contrast 15 of the 18 Rotterdam
      strains possessed a plasmid mediated beta-lactamase, ten of which were TEM-2.
      Eight of the ten strains with the TEM-2 enzyme harboured a transferable plasmid
      coding for resistance to piperacillin. Endonuclease analysis of plasmid DNA from
      these eight strains revealed an identical pattern in seven strains. Different
      selective pressures were operative in each hospital. In Amsterdam the general use
      of cefotaxim and piperacillin favoured emergence of strains with derepressed
      chromosomal Class 1 beta-lactamase, whereas in Rotterdam the use of cefuroxime
      favoured the spread of a plasmid, encoding TEM-2 beta-lactamase.

PMID- 18611804
TI  - Comparative in vitro activities of rifamycin analogues against rifampin-sensitive
      and rifampin-resistant Mycobacterium tuberculosis.
AB  - Because of widespread emergence of multidrug resistant Mycobacterium tuberculosis
      worldwide, there is an urgent need for new bactericidal drugs against this
      organism. Several new analogues of rifamycin are being developed.
      Susceptibilities of five of the most potent analogues were determined
      simultaneously on ten isolates each of rifampin-sensitive and rifampin-resistant
      M. tuberculosis using the radiometric method (BACTEC) with [C(14)]palmitic acid.
      Against rifampin-sensitive isolates, all five analogues exhibited inhibitory
      activity, the most potent being KRM-1648, with MICs varying between 0.003 and
      0.02S mug/ml (MICs of rifampin were between 0.05 and 0.4 mug/ml). Similar
      observations were also obtained for the MBCs of these five analogues-KRM-1648 was
      most potent, with nine out of ten isolates exhibiting a MBC/MIC ratio of 1.0.
      Among the rifampin-resistant isolates of M. tuberculosis, the most potent
      rifampicin analogue was, again, KRM-1648, with seven out of ten isolates
      exhibiting MBC/MIC ratio of 1.0 and the remaining three exhibiting a ratio of
      2.0. These results suggests that KRM-1648 should further be explored in the
      treatment of tuberculosis patients.

PMID- 18611805
TI  - Netilmicin serum levels in 138 cancer patients. Do they predict nephrotoxicity or
      therapeutic failure?

PMID- 18611806
TI  - Aerobic gram-negative bacilli: newer nosocomial pathogens.

PMID- 18611807
TI  - Treatment of infections caused by highly resistant enterococci.
AB  - Antibiotic-resistant enterococci have become an increasingly important cause of
      nosocomial infections, frequently involved in hospital outbreaks. Acquired
      antibiotic resistance among enterococci include high-level aminoglycosides, beta
      lactams and glycopeptide resistance. Vancomycin-resistant enterococci (VRE) have
      had a major impact in the USA and are now widely distributed among different
      European countries. The treatment of VRE infections is usually difficult and
      relatively inefficient, leading to failure of antibiotic therapy and surgery for
      uncontrolled sepsis. Since there is often no therapeutic agent available of
      established efficacy for patients infected by VRE, in vitro studies and animal
      models represent useful tools to test new antibiotic molecules and to evaluate
      the efficacy of new antibiotics given alone or in association.

PMID- 18611808
TI  - Influence of adjunct azithromycin on the mortality of experimental Pseudomonas
      aeruginosa sepsis.
AB  - The aim of this study was to determine the in vivo influence of azithromycin
      subinhibitory concentrations on mortality in a peritonitis-sepsis model. One hour
      after an intraperitoneal injection of Pseudomonas aeruginosa, mice were
      randomized to receive: ceftazidime, 500 mg/kg SC q4hxtwo doses alone;
      azithromycin, 20 mg/kg SCxone dose alone; ceftazidime plus azithromycinxone dose;
      ceftazidime plus azithromycinxtwo doses (1 and 24 h); ceftazidime plus
      prophylactic azithromycin (three doses at -48, -24, 1 h); or no treatment
      (control). A significant decrease in the rate of mortality was observed in
      animals treated with all ceftazidime plus azithromycin groups when compared with
      those receiving ceftazidime alone. These data indicate a potential role for
      adjunctive azithromycin therapy in P. aeruginosa infection.

PMID- 18611809
TI  - Antimicrobial activity and durability of a novel antimicrobial-impregnated
      bladder catheter.
AB  - The main objective of this study was to examine the antimicrobial activity and
      durability of a novel indwelling bladder catheter impregnated with minocycline
      and rifampin. Thirty antimicrobial-impregnated bladder catheters were inserted
      transurethrally in spinal cord-injured patients and removed, in six groups of
      five catheters each, at 3, 7, 10, 14, 17 or 21 days. Removed catheters had
      detectable zones of inhibition against two different clinical isolates of each of
      the 10 tested uropathogens (Escherichia coli, Pseudomonas aeruginosa, Proteus
      mirabilis, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter diversus,
      Enterococcus faecalis, Enterococcus faecium, Staphylococcus saprophyticus and
      Candida albicans) for greater than 14 days after catheter insertion. The residual
      zones of inhibition and levels of antimicrobial agents in removed catheters were
      both inversely related to the duration of catheter placement. Minocycline and
      rifampin were undetectable in serum and urine. These results support the ongoing
      efforts for examining the clinical efficacy of these experimental bladder
      catheters.

PMID- 18611810
TI  - Evaluation of in vitro activity of a new fluoroquinolone trovafloxacin (cp
      99,219) compared with other anti-anaerobic antimicrobials against members of the
      Bacteroides fragilis group.
AB  - The in vitro activity of a new fluoroquinolone, trovafloxacin (CP-99,219) was
      compared with that of ten other agents against 100 clinical isolates in the
      Bacteroides fragilis group. Trovafloxacin was the most active quinolone (MIC(90),
      1 microg/ml) followed by sparfloxacin (MIC(90), 8 microg/ml), levofloxacin
      (MIC(90), 16 microg/ml) and ofloxacin (MIC(90), 32 microg/ml). Ciprofloxacin was
      the least active quinolone (MIC(90), 64 microg/ml). Metronidazole,
      chloramphenicol, imipenem and piperacillin/tazobactam, showed excellent activity
      with an MIC(90) of 1, 8, 0.25 and 16 microg/ml, respectively. Cefoxitin showed
      good activity and piperacillin was the least active compound. B. vulgatus and B.
      ovatus were the most resistant species to trovafloxacin among those of the
      B.fragilis group with an MIC(90) of 4 microg/ml while B. fragilis and B.
      thetaiotaomicron were the most susceptible (MIC(90), 1 microg/ml).

PMID- 18611811
TI  - HPLC residues of enrofloxacin and ciprofloxacin in eggs of laying hens.
AB  - Eggs of 12 laying hens with 5 mg/kg/day oral administration of 5% enrofloxacin
      (EFX) or ciprofloxacin (CFX) solution during 5 days contained residues from 0.02
      to 1.98 microg/g (EFX) or 0.14 to 0.28 microg/g (CFX). At identical dosage regime
      High Performance Liquid Chromatograhy (HPLC) residues of EFX were 6-fold greater
      than CFX ones. Maximun concentrations were detected at the second day after the
      administration withdrawal. The limits of detection were 0.019 microg/g for EFX
      and 0.156 microg/g for CFX. The recovery was 36-50% for CFX and 49-85% for EFX.
      The withdrawal treatment periods in hens are six days for EFX and five days for
      CFX in order to avoid violative levels of egg residues.

PMID- 18611812
TI  - Comparative efficacy of successive exposure of Pseudomonas aeruginosa to
      gentamicin and ceftazidime.
AB  - Aminoglycoside and beta-lactam antibiotics, when used in combination, are usually
      given simultaneously, however, successive administration may be more efficient.
      The killing capacity was used to assess the effect of time intervals between low
      and high concentrations (2-8xMICs) of gentamicin and/or ceftazidime on
      Pseudomonas aeruginosa and to determine which drug is better to be administered
      first. The killing capacity after exposure to the antibiotic for 1 h were
      compared: (i) cells treated with gentamicin alone; (ii) cells treated with
      ceftazidime alone; and (iii) ceftazidime was added to (i) or (iv) gentamicin was
      added to (ii) at 0, 1 and 3 h of antibiotic removal. The bactericidal activity of
      gentamicin was potentiated and the viable cells decreased up to 6 h after
      antibiotic removal when the ceftazidime was added at O and at 1 h but the extent
      of bactericidal activity was reduced, when it was added at 3 h after gentamicin
      removal. Alternatively, treating the cells first with ceftazidime and then
      gentamicin was added after drug removal at O and at 1 h resulted in a marked
      decline in the viable cells, while addition of gentamicin after 3 h from
      ceftazidime removal, the extent of bactericidal activity was reduced. The non
      treated cells with gentamicin started to grow heavily within 6 h of ceftazidime
      removal. No viable cells were detected after overnight incubation in cultures
      treated first with 6 or 8xMIC of gentamicin for 0.5 or 1 h. This in vitro study
      suggests that the optimum interval between gentamicin and ceftazidime doses,
      which gave the maximum bactericidal effect and the time before re-growth,
      appeared to be 1-2 h.

PMID- 18611813
TI  - Consensus on the use of neutrophil-stimulating hematopoietic growth factors in
      clinical practice: an international viewpoint.
AB  - Hematopoietic growth factors (CSFs) are now available for use in patients with
      myelosuppression due to congenital, acquired and therapy-induced conditions.
      Variations in the use of granulocyte colony-stimulating factor (G-CSF) and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) in different countries
      are due to differences in approved indications by national regulatory agencies,
      varying opinions on the importance of certain treatment outcomes, differences in
      the selection of published and unpublished evidence of efficacy and the impact of
      the cost of these agents in different health care systems. Through Medline
      searches and personal files, we have reviewed the published literature on the
      efficacy and cost of GM-CSF and G-CSF in patients with severe chronic neutropenia
      and those receiving standard dose chemotherapy or high-dose chemotherapy
      requiring bone marrow reconstitution. Guidelines were established with regard to
      (1) the relative merits of different types of clinical studies and (2) the
      relative importance of different clinical outcomes as reported in these studies.
      The cost implications of these agents as they apply to the different clinical
      settings are also reviewed. Recommendations for the use of G-CSF and/or GM-CSF
      include: (1) the prevention of recurrent, debilitating infections in patients
      with severe chronic neutropenia; and (2) the maintaining of dose-intensity of
      potentially curative, standard-dose chemotherapy. While G-CSF and/or GM-CSF have
      been shown to improve secondary outcomes in higher-than-standard dose-intensive
      therapy, further studies are needed to test whether such improvements also lead
      to significant improvements in survival and/or quality of life. These
      recommendations are based on the collective interpretation of the presented
      evidence by an international group of investigators in this area.

PMID- 18611814
TI  - Bacteremia due to Enterobacter spp. in cancer patients--analysis of 51 episodes.
AB  - Fifty one episodes of bacteremia due to Enterobacter spp. appearing within 7
      years among 12 301 admissions in a single cancer institution were studied for
      risk factors, clinical presentation and outcome. Fifteen episodes were due to
      Enterobacter aerogenes, 23 due to E. cloacae and 13 due to E. agglomerans. The
      proportion of bacteremia due to Enterobacter spp. among Gram-negative bacteremias
      was 10.1% and infection associated mortality was 13.8%. The incidence in 1989
      1995 varied from 3.7 to 8.7% and was relatively stable. Most common risk factors
      were: solid tumors as underlying disease, central venous catheter insertion,
      prior surgery and prior chemotherapy within 48 h. Neutropenia and urinary
      catheters were not at high risk in either one of the patients subgroups.
      Comparing two subgroups of 51 bacteremias, monomicrobial and polymicrobial (when
      Enterobacter spp. was isolated from blood culture with other microorganism),
      previous chemotherapy, vascular catheter insertion and prior endoscopy were more
      frequently associated with polymicrobial Enterobacter spp. bacteremia. There was
      also differences in infection associated mortality: bacteremias due to
      Enterobacter spp. only had significantly lower mortality in comparison to
      polymicrobial Enterobacter spp. bacteremias (3.3 vs. 29.3%; P<0.02).
      Susceptibility of Enterobacter spp. strains isolated from 51 episodes was stable
      and showed only two episodes due to quinolone-resistant strains, both in 1992
      despite of the use of ofloxacin in prophylaxis of neutropenic patients since 1990
      in our institute. Ninety-two to 94% of all strains were susceptible to
      aminoglycosides, 96-98% to ofloxacin and ciprofloxacin, respectively and 94.9% to
      meropenem but only 75.5% to ceftazidime.

PMID- 18611815
TI  - Antibiotics for treatment of infections caused by MRSA and elimination of MRSA
      carriage. What are the choices?
AB  - The widespread appearance of methicillin resistant Staphylococcus aureus (MRSA)
      has significantly undermined the efficacy of currently available antibiotic
      therapies as strains tend to be multi-resistant. Clinicians are therefore faced
      with a restricted choice in effective anti-MRSA therapies for infection or
      elimination of carriage. MRSA remain uniformly susceptible to glycopeptides
      vancomycin and teicoplanin which remain drugs of choice in treatment of
      infections. Centres with a high incidence of MRSA should use glycopeptides as
      empirical monotherapies against these organisms. The low toxicity of teicoplanin
      makes it an alternative for patients unable to tolerate vancomycin. Only
      mupirocin is truly effective for use as a topical agent in elimination of MRSA
      colonisation. For systemic use developmental glycopeptides such as daptomycin,
      MDL 63246, and LY191145 show better in vitro activity than vancomycin. New
      cephalosporins TOC-39 and FK-037 show promising anti-MRSA potential with low
      MICs, as does carbapenem BO-2727 which has a high in vitro activity. Whether the
      new cephalosporins and carbapenems with good in vitro and/or in vivo activities
      against MRSA will be clinically effective remains to be determined. New
      fluoroquinolones levofloxacin, temafloxacin and sparfloxacin have enhanced in
      vitro anti-MRSA activity, although the emergence of resistance, and subsequent
      cross resistance to related compounds during therapy is a problem. BAY 12-8039,
      DV-7751 and CS-940 are developmental fluoroquinolones with better in vitro
      activity and lower spontaneous mutation rates than related compounds. Co
      trimoxazole shows good in vivo anti-MRSA activity, comparable to vancomycin,
      however, severe infections do not respond well and many strains are resistant to
      this drug. Rifampicin has excellent bactericidal activity but rapidly emerging
      resistance undermines its use as a monotherapy. Its use in a combination therapy
      offers limited potential as an alternative. Arbekacin shows good in vitro
      activity against many MRSA isolates, although resistance to related
      aminoglycosides is a problem. Streptogramins, virginiamicin and RP 59500
      (dalfopristin/quinupristin), and the everninomicin SCH 27899, show excellent
      activity in vitro and in vivo activity against MRSA and real future potential as
      alternative agents to vancomycin. Azeleic acid and ramoplanin show future
      potential as agents for topical use against MRSA. In conclusion only vancomycin
      as a systemic agent and mupirocin as a topical agent, offer sufficient
      reliability for use against MSRA. Alternatives to glycopeptides and mupirocin
      rest with the development of new drugs from several classes of compounds.

PMID- 18611816
TI  - Development of resistance of human immunodeficiency virus (HIV) to anti-HIV
      agents: how to prevent the problem?
AB  - Of the multitude of reverse transcriptase inhibitors and protease inhibitors that
      have been pursued for the treatment of HIV infections, nine compounds (viz.
      zidovudine, didanosine, zalcitabine, stavudine, lamivudine, saquinavir,
      ritonavir, indinavir and nevirapine) have been approved and several others (i.e.
      adefovir dipivoxyl [bis(POM)-PMEA], PMPA, bis(POC)-PMPA, 1592U89, delavirdine,
      loviride, MKC-442, nelfinavir and VX-478) are under clinical development. All
      these compounds can select for mutations in the reverse transcriptase or protease
      that confer various degrees of resistance or diminished susceptibility to the
      compounds. Both the reverse transcriptase and protease are able to accumulate
      multiple mutations in their genome, thus engendering high-level resistance. To
      avoid drug resistance from emerging it is recommended to use from the beginning
      combinations of the different drugs at sufficiently high (that is maximal
      tolerated) doses. If installed as soon as possible after infection, when it has
      become evident that the virus is replicating, these drug combinations may achieve
      a pronounced and sustained virus suppression. This should be reflected by a
      dramatic reduction of viral load in both the plasma and lymphnodes. With the most
      effective drug combination regimens, the viral load may even fall under the
      threshold of detection, and this may clinically translate into an arrest or
      prevention of progression to AIDS.

PMID- 18611817
TI  - Management of osteomyelitis.
AB  - Early diagnosis and aggressive treatment, which includes thorough debridement and
      culture-directed antibiotic therapy, are essential for effective management of
      patients with osteomyelitis. Definitive diagnosis of osteomyelitis usually
      requires microbial culture of bone specimens obtained either by surgery or by
      percutaneous needle biopsy. The most common pathogen involved in osteomyelitis is
      Staphylococcus aureus; however, other organisms, including gram-negative
      pathogens and coagulase-negative staphylococci, may be found. Often, bone
      infections may be polymicrobial. Antimicrobial therapy, ideally initiated after
      complete surgical debridement and microbial confirmation of the diagnosis, is
      usually maintained for at least 6 weeks. Although therapy has traditionally been
      administered parenterally during an extended hospital stay, oral antibiotic
      therapy (often following initial parenteral therapy) and parenteral therapy on an
      outpatient basis are gaining acceptance for use in patients with osteomyelitis.

PMID- 18611818
TI  - Antimicrobial treatment of upper respiratory tract infections from the Dutch
      perspective.
AB  - The worldwide problem of multiple resistant strains should be attacked by a more
      adequate, rational prescription behaviour of antibiotics. As most upper
      respiratory tract infections (URTIs) have a viral cause and are selflimiting,
      antibiotics should be used for certain indications only. The development of
      evidence based guidelines, based on outcome studies in the field of URTIs carried
      out in general practice populations is recommended. The general practitioners
      (GPs) with defined practice populations are in a key position for research and a
      restrictive antibiotic policy. Several RCTs are carried out in general practice
      indicating that antibiotic prescriptions can be reduced. This will contribute to
      the decrease of resistant strains.

PMID- 18611819
TI  - Antiviral activity of meliacine on the replication of a thymidine kinase
      deficient mutant of Herpes simplex virus type 1 alone and in combination with
      acyclovir.
AB  - The anti-HSV-1 activity of meliacine (MA), a peptide isolated from leaves of
      Melia azedarach L., alone and in combination with acyclovir (ACV), was assayed
      against thymidine kinase-deficient (TK(-)) virus yields in vitro. MA alone proved
      to inhibit significantly TK(-) viral replication, whereas ACV was more potent
      than MA as an inhibitor of TK(+) replication. TK(-) and TK(+) synergistic
      inhibition by the combination of both agents was observed at concentrations that
      did not alter cell viability. The interaction between MA and ACV was
      quantitatively determined by calculating the combination index and plotting the
      data by the isobologram method. Besides, MA and ACV were able to suppress
      synergistically the antigen expression on HSV-I infected cells processed by an
      immunofluorescence assay. These in vitro findings suggest that combinations of MA
      and ACV at appropriate doses may provide an increased efficacy in inhibiting both
      TK(-) and TK(+) HSV-1 multiplication.

PMID- 18611820
TI  - In vitro anti-trichomonad effectiveness of a gossypol-metronidazol blend.
AB  - With the aid of the Basic Sequential Analytical Simplex Method the in vitro anti
      trichomonad effectiveness of several metronidazole/gossypol blends was
      determined. While the combination that produced 50% of growth inhibition on
      trichomonad cultures (IC50) contained 15.1 microM gossypol and 0.087 microM
      metronidazole, the IC(50) of metronidazole and gossypol tested separately was
      38.08 microM and 0.195 microM, respectively. Thus, the IC50 of mixed gossypol and
      metronidazole was, respectively 60.34 and 55.4% lower than that of each separated
      drug. Whereas metronidazole is usually administered orally, gossypol, used as
      spermicide, is formulated as pessary. In such conditions the absorption of
      metronidazole is very efficient while that of gossypol is strikingly poor. The
      above suggest that a gossypol-metronidazole anti-trichomoniasis therapeutic
      scheme could be as effective as metronidazole alone, but less toxic.

PMID- 18611821
TI  - Intracellular organisms.
AB  - The intracellular location of some microorganisms allow them to resist
      antibiotics with poor ability to penetrate eukaryotic cell membranes, such as the
      beta-lactam compounds. Pharmacokinetic and pharmacodynamic properties of
      antibiotics within eukaryotic cells have been defined in the last two decades.
      Penetration but also subcellular localization of antibiotics within cells, as
      well as the possibility of their intracellular inactivation have to be
      considered. In vitro infected cell models have been useful to determine the
      activity of antibiotics against intracellular pathogens, although extrapolation
      of in vitro experimental data to the clinical situation remains hazardous. The
      pharmacokinetic properties and intracellular activity against a number of
      pathogens of the newer fluoroquinolone and macrolide compounds seems promising,
      but clinical data remain scarce.

PMID- 18611822
TI  - Contribution of animal models of infection for the evaluation of the activity of
      antimicrobial agents.
AB  - Animal models of infection should be considered as tools that may be used for
      many different purposes: investigation of the physiopathology and natural history
      of infection on one hand, evaluation of the toxicity, pharmacokinetics and
      activity of antimicrobials on the other hand. Many review articles on the use of
      animal models of infection for the evaluation of antimicrobial agents have been
      published (Zak O, O'Reilly T. Animal models in the evaluation of antimicrobial
      agents. Minireview. Antimicrob Agents Chemother 1991;35:1527-1531), including a
      recent comprehensive review (O'Reilly T, Cleeland R, Squires E. Evaluation of
      antimicrobial s in experimental animal infections. In: Lorian V, editor.
      Antibiotics in Laboratory Medicine, 4th ed. Williams and Wilkins, Baltimore,
      1996: 599-759). Therefore, this article will only focus on the contribution of
      the animal models of infection in: (i) the evaluation of the in vivo activity of
      antimicrobial agents, using a pharmacodynamic approach. For this purpose, animal
      models are used to quantify the in vivo bacterial killing and to investigate the
      different factors influencing the final in vivo activity. (ii) The investigation
      of the non response to antimicrobial agents in vivo. In this case, animal models
      are used to investigate the factors limiting the in vivo activity of
      antimicrobial agents.

PMID- 18611823
TI  - Management of chronic bronchitis and acute exacerbations of chronic bronchitis.
AB  - Chronic bronchitis and its complications is one of the most common causes of
      visits to physicians. Prevention of both disease progression and infectious
      exacerbations lies mainly with smoking cessation and vaccination strategies.
      Medical therapy of the disease may improve symptoms but has not been shown to
      alter the natural history. Bacterial pathogens account for the majority of
      infectious flares of the disease but the presence of chronic airway colonization
      makes it difficult to separate pathogens from commensal organisms. The choice of
      antimicrobial therapy to treat infectious exacerbations should be based on a
      combination of patient's age, severity of underlying airflow obstruction,
      frequency of exacerbations and the presence of other underlying diseases which
      increase the risk of treatment failure.

PMID- 18611824
TI  - Microbially-produced peptides having potential application to the prevention of
      dental caries.
AB  - Strategies advanced to decrease the occurrence of dental caries have in the past
      typically focussed upon attempting to reduce plaque accumulation by application
      of broad-spectrum antibacterial agents. In recent years however there has been
      growing interest in the application of a more targeted approach to the selective
      elimination from plaque of those bacterial species that are specifically
      implicated as the aetiological agents of this disease. This review focuses upon a
      number of the small bacterially-produced peptide antibiotics known as
      bacteriocins that are currently being explored for their potential role in the
      treatment and prevention of dental caries.

PMID- 18611825
TI  - Antibiotic resistance patterns in Pseudomonas aeruginosa: an 8-year surveillance
      study in a French hospital.
AB  - The susceptibility to ticarcillin, piperacillin, ceftazidime, aztreonam,
      tobramycin, amikacin, ciprofloxacin and fosfomycin of 3876 strains of Pseudomonas
      aeruginosa isolated during the period 1989-1996 in a French hospital was
      investigated. The most frequently active agents were amikacin and ceftazidime to
      which 13.3% and 16.1% of the isolates were resistant. Analysis of beta-lactam
      susceptibility patterns suggested that cephalosporinase derepression and
      intrinsic resistance were the predominant underlying mechanisms. There was a
      trend towards a decline in susceptibility to beta-lactams, aminoglycosides and
      ciprofloxacin over time. Multiresistance was frequent, mainly in O11 and O12
      isolates.

PMID- 18611826
TI  - Correlation of erythromycin agar dilution susceptibility testing with disc
      diffusion susceptibility for Bordetella pertussis.
AB  - Agar dilution and disc diffusion susceptibility testing of erythromycin were
      performed for contemporary isolates of Bordetella pertussis with the use of
      charcoal media. Minimum inhibitory concentration (MIC) values ranged from < or =
      0.016-0.5 mg/l and the MIC(50) and MIC(95) were 0.125 and 0.25 mg/l respectively.
      Disc diffusion zone sizes were interpretable after either 48 or 72 h of
      incubation and all inhibition diameters were > or = 37 mm.

PMID- 18611827
TI  - Antibacterial activity of hydrocele fluid.
AB  - We determined whether hydrocele fluid suppresses the growth of bacteria.
      Hydrocele fluid was obtained by needle aspiration from 25 patients with
      idiopathic hydrocele. Escherichia coli (10(5)-10(6) cells) was inoculated into
      the fluid (10 ml) and the bacterial number in the fluid was counted for 24 h. In
      most of the fluids the bacterial number increased for the first 2-12 h and then
      gradually decreased to a level below the inoculum number. In the fluids that had
      been bathed at 56 degrees C for 30 min, the bacterial number continued
      increasing. These results suggest that hydrocele fluid mostly possesses
      antibacterial activity and also, that complement in the fluid may participate in
      this activity.

PMID- 18611828
TI  - In vitro activity of meropenem against organisms causing serious infections in a
      Singapore hospital.
AB  - Meropenem (MEM) is a carbapenem antibiotic effective against infections caused by
      a variety of organisms. This study was conducted to evaluate MEM, which has not
      been previously used in the hospital, in parallel with some antimicrobial agents
      now in use, against organisms causing serious infections in the hospital. A total
      of 382 organisms isolated from blood cultures were included in the study. In the
      case of Bacteroides spp. and Burkholderia pseudomallei, organisms recovered from
      blood as well as from other sites were also included. In addition to MEM, 12
      antimicrobial agents were tested against Gram-negative bacilli and seven against
      staphylococci. Antimicrobial susceptibility testing was carried out by the Kirby
      Bauer disc diffusion technique based on the M2-A4 standard. The present paper
      demonstrates that meropenem, imipenem and ciprofloxacin are the most active
      antimicrobial agents against clinically important organisms causing serious
      infections in the hospital.

PMID- 18611829
TI  - Activities of ciprofloxacin, levofloxacin, ofloxacin and sparfloxacin against
      speciated coagulase-negative staphylococci sensitive and resistant to
      fluoroquinolones.
AB  - A total of 119 strains of coagulase-negative staphylococci isolated from clinical
      specimens were speciated and tested for sensitivity to methicillin and four
      fluoroquinolones (ciprofloxacin, sparfloxacin, levofloxacin and ofloxacin).
      Resistance to fluoroquinolones was significantly more common in Staphylococcus
      haemolyticus (43%) than in Staphylococcus epidermidis (11%). Methicillin
      resistant strains of S. haemolyticus were more often resistant to ciprofloxacin
      than were methicillin-resistant strains of S. epidermidis (P < 0.05).
      Sparfloxacin was the most active against fluoroquinolone-sensitive strains, and
      levofloxacin was twice as active as ofloxacin. There was cross-resistance between
      the four fluoroquinolones. Levofloxacin was the most active against resistant
      strains, but MICs obtained for all the compounds seemed to be outside the
      clinically useful range for the treatment of systemic infections.

PMID- 18611830
TI  - Pharmacokinetics of intracellular zidovudine and its phosphorylated anabolites in
      the absence and presence of stavudine using an in vitro human peripheral blood
      mononuclear cell (PBMC) model.
AB  - Both zidovudine (ZDV) and stavudine (D4T) must be intracellularly converted to
      their respective active triphosphate anabolites (ZDV-TP and D4T-TP). It is
      hypothesized that the combination of ZDV and D4T may lead to altered formation of
      phosphorylated anabolites for either drug. The objective of this study was to
      investigate the effect of D4T on intracellular ZDV phosphorylation. Human PBMCs
      were incubated with [(3)H]ZDV in the presence and absence of D4T. Cells were
      harvested at several time points over 12 h to determine area under the
      intracellular concentration versus time curve (AUC) of ZDV and its phosphorylated
      anabolites. Radiolabled ZDV and anabolites were quantified using HPLC and LS. The
      AUC for ZDV-TP was 0.53 and 0.52 pmol x h/10(6) PBMC in the absence and presence
      of D4T, respectively. The AUC for ZDV monophosphate was 157.45 and 172.44 pmol x
      h/10(6) PBMC pre and post D4T. D4T does not appear to affect the formation of
      intracellular ZDV phosphates in human PBMCs under the conditions studied.

PMID- 18611831
TI  - In vitro activities of cefepime versus cefotaxime and ceftriaxone against
      penicillin-resistant Streptococcus pneumoniae determined by Etest.
AB  - The Etest was used for determining in vitro susceptibilities of 144 unique
      clinical isolates of penicillin-intermediate and resistant Streptococcus
      pneumoniae to cefepime, cefotaxime, and ceftriaxone. MIC ranges were 0.12-8
      mug/ml for cefepime and 0.06-16 mug/ml for cefotaxime and ceftriaxone. MICs for
      50% of the isolates for the three agents were equivalent at 1 mug/ml, whereas
      MICs for 90% of the isolates were 2 mug/ml for cefotaxime and ceftriaxone, versus
      4 mug/ml for cefepime. The Etest is a practical means for determining
      susceptibilities of S. pneumoniae to cefepime and other cephalosporins in
      diagnostic laboratories.

PMID- 18611832
TI  - [The role of advanced cardiac imaging methods in coronary artery disease].
AB  - Evaluation of the myocardial perfusion and the structures of coronary arteries
      with the use of various high technologies, such as advanced echocardiography,
      magnetic resonance tomography, spiral computed tomography as well as large
      spectrum of techniques of nuclear cardiology, gains more and more important
      significance in the diagnosis and management of coronary artery disease.
      Detection of coronary atherosclerosis and evaluation of early signs of myocardial
      hypoperfusion provide to select effective treatment modality. Nuclear cardiac
      studies are being frequently used in this field. In asymptomatic and intermediate
      likelihood patients, assessment of myocardial perfusion by single photon emission
      computed tomography (SPET) or positron emission tomography (PET) appears to be
      valuable even when coronary arteries are normal. Different imaging protocols and
      radiopharmaceuticals allow us to evaluate ventricular functions and myocardial
      metabolic state besides of myocardial perfusion. In this plane, definite
      successes are being achieved by PET and combined acquisitions by PET/CT and
      SPET/CT hybrid systems. Coronary computed tomography angiography (CTA) and
      myocardial perfusion imaging provide complementary information on vascular
      structure and myocardial perfusion. However, CTA with fast 16-slice or greater
      scanners may emerge as the initial test of choice. Myocardial perfusion studies
      would then be used if the CTA is not available or to assess how a stenosis
      defined by CTA effects coronary supply. Spiral computed tomography which allows
      to reveal calcium depositions in blood vessels has an important role in the
      detection of the severity and extent of atherosclerotic lesions. The use of
      multislice computed tomography in perspective might partially replace coronary
      angiography especially for assessing the degree of stenosis and patency of
      grafts. Magnetic resonance imaging (MRI) also has provided noticeable success in
      this era. Cardiac MRI clearly has the potential for this application and has
      already emerged as a highly effective method for assessing ventricular function,
      myocardial mass and myocardial viability. There is an increasing use of this
      approach for clinical rest and stress perfusion measurements. While cardiac MRI
      angiography (CMRA) has great promise as a radiation-free, it currently lags
      behind CTA for noninvasive coronary angiography. Further perfection of equipment
      and methodological approaches with the use of novel contrasts is necessary. In
      patients with coronary artery disease, multimodality applications covering both
      morphological and functional assessment are helpful for diagnosing and planning
      of therapeutic strategy. Recent developments in the field of ultrasonography have
      allowed us objectively quantify global and regional ventricular function, and to
      get real-time evaluation of coronary walls and lesions. While we achieve more
      knowledge about atherosclerotic lesions by using intravascular ultrasound
      technique, tissue Doppler imaging has given us attempt to provide a more
      objective assessment of myocardial function. Finally, although CTA and CMRA are
      likely to grow considerably in diagnostic evaluation over the next several years,
      myocardial perfusion studies with SPET and PET equipment will continue to be very
      valuable techniques for this purpose.

PMID- 18611833
TI  - [Myocardial perfusion scintigraphy in the diagnosis and prognostic assessment of
      coronary artery disease: SPET and PET].
AB  - In this article, the role of nuclear cardiology modalities in the diagnosis and
      follow-up of ischemic coronary artery disease in respect of myocardial perfusion
      and determination of left ventricular ejection fraction are reviewed. Single
      photon emission tomography (SPET) and positron emission tomography (PET)
      techniques are applied for imaging of myocardial perfusion and evaluation of
      global and regional wall motion and contractility. These techniques could be
      applied with physiological or pharmacological stress and show different
      properties when compared to other imaging modalities mostly depending on
      anatomical details. Diagnostic value of myocardial perfusion scintigraphy and
      incremental value of SPET or PET/CT (computerized tomography) hybrid imaging is
      considered. Nuclear cardiology techniques may provide useful prognostic
      information besides their diagnostic use.

PMID- 18611834
TI  - [Coronary artery calcium scoring method].
AB  - Considering that coronary artery disease (CAD) is the number one cause of death
      in the developed countries and higher than half of patients with severe clinical
      symptoms do not have any predictive sign for CAD necessitate the development of
      advanced screening tests. Coronary artery calcium score (CCS) test depending on
      the principle of measurement of calcium level in atherosclerotic lesions is one
      of the most important steps in this field. Coronary artery calcification is
      recognized as an active process that is closely linked to vascular inflammation
      and predicts future cardiac events. Presence of calcium in vascular lesions
      allows us to assess the lesion burden. Nowadays spiral CT is being widely used to
      define structural changes and calcium deposition in coronary artery segments
      instead of electron beam tomography which is initially used. However, since there
      are numerous non-calcified lipid-rich plaques with thin fibrous caps besides
      calcified plaques in CAD patients, CCS is not efficient test to evaluate the risk
      of CAD alone. The CCS percentiles defined for age and gender are more relevant in
      assessing risk and more predictive of hard cardiac events than absolute CCS. In
      asymptomatic cases, while being zero of CCS do not eliminate the risk of
      occurring acute cardiac events and the possibility of myocardial ischemia, the
      presence of high CCS rises predictive value of Framingham risk score (FRS) for
      coronary death and non-fatal myocardial infarction. Finally, the CCS is valuable
      test screening tool in selected patients such as those with an intermediate FRS,
      as recommended by the current guidelines; high coronary calcium score is closely
      related with the increased risk of CAD and serious cardiac events, and signs to
      requirement for secondary prevention and other advanced techniques in the
      diagnosis of CAD.

PMID- 18611835
TI  - [Utilization of intravascular ultrasound in coronary artery disease].
AB  - Intravascular ultrasound (IVUS) that found a significant place for itself in
      cardiac imaging area in recent years was able to penetrate into the field of use
      thanks to putting the ultrasound probe in the tip of catheter, which can navigate
      through the vein by miniaturizing it on a much smaller scale than we used to see.
      Various recent scientific studies showed IVUS is a valuable tool in assessing the
      natural course of coronary atherosclerosis and effects of different
      pharmacological and non-pharmacological approaches on the progression-regression
      of atherosclerosis. In addition, IVUS is also applied in studies evaluating the
      short- and long-term outcomes of different percutaneous coronary interventions
      including the implantation of drug-eluting stents.

PMID- 18611836
TI  - [The role of Doppler echocardiography in the evaluation of myocardial ischemia
      and regional function abnormalities in patients with coronary artery disease].
AB  - Recent developments in the field of echocardiography have allowed us objectively
      quantify global and regional myocardial function. The first developed technology;
      tissue Doppler imaging provides a more objective assessment of myocardial
      function but it is subject to cardiac translational motion and passive tethering
      effects. These limitations are overcome by the measurement of local myocardial
      deformation parameters with strain and strain rate echocardiography. These
      methods are valid not only during baseline regional ischemia assessment but also
      during stress echocardiography.

PMID- 18611837
TI  - [Multislice computerized tomography coronary angiography: general principles,
      technique and clinical applications].
AB  - Electrocardiogram-gated coronary multislice computerized tomography (CT)
      angiography is a rapidly improving technology allowing noninvasive imaging of
      coronary arteries. After the initial promising results obtained with four-section
      CT scanners, progressively higher temporal and spatial resolutions have been
      achieved by increasing gantry rotation speed and the number of detector rows and
      by reducing individual detector size. This review presents an overview of the
      general principles, technique and emerging applications and artifacts of coronary
      multislice CT angiography. The diagnostic performance of this new technology
      allows it to be used to evaluate the presence of coronary plaques and stenosis,
      coronary bypass graft patency, and the origin and course of congenital coronary
      anomalies. As it visualizes coronary artery wall in addition to lumen and
      provides volumetric data of heart and great vessels, it readily demonstrates
      plaque remodeling, ostial lesions and other cardiac and extracardiac
      abnormalities. The high negative predictive value of coronary CT angiography
      makes it a valuable tool in the evaluation of patients with low or intermediate
      pretest probability for coronary artery disease. However, improvements in spatial
      and temporal resolution are still needed in the imaging of small coronary stents,
      in the detection and characterization of noncalcified plaques, and to overcome
      image degradation by arrhythmias, higher heart rates, and calcium-related
      artifacts.

PMID- 18611838
TI  - [Cardiac magnetic resonance imaging in evaluation of coronary artery disease].
AB  - Considerable advances have been achieved in cardiovascular magnetic resonance
      imaging (MRI) technology, and MRI has become an important noninvasive imaging
      tool in the management of coronary artery disease. Cardiac MRI can provide
      information about myocardial perfusion, viability and contractile reserve. The
      information obtained not only provides diagnostic information but also has an
      important prognostic value. This article reviews the recent advances in cardiac
      MRI for evaluation of coronary artery disease.

PMID- 18611839
TI  - Candidate neural locus for sex differences in reproductive decisions.
AB  - Sexual selection and signal detection theories predict that females should be
      selective in their responses to mating signals in mate choice, while the response
      of males to signals in male competition should be less selective. The neural
      processes underlying this behavioural sex difference remain obscure. Differences
      in behavioural selectivity could result from differences in how sensitive sensory
      systems are to mating signals, distinct thresholds in motor areas regulating
      behaviour, or sex differences in selectivity at a gateway relaying sensory
      information to motor systems. We tested these hypotheses in frogs using the
      expression of egr-1 to quantify the neural responses of each sex to mating
      signals. We found that egr-1 expression in a midbrain auditory region was
      elevated in males in response to both conspecific and heterospecific calls,
      whereas in females, egr-1 induction occurred only in response to conspecific
      signals. This differential neural selectivity mirrored the sex differences in
      behavioural responsiveness to these stimuli. By contrast, egr-1 expression in
      lower brainstem auditory centres was not different in males and females. Our
      results support a model in which sex differences in behavioural selectivity arise
      from sex differences in the neural selectivity in midbrain areas relaying sensory
      information to the forebrain.

PMID- 18611840
TI  - A keystone effect for parasites in intraguild predation?
AB  - Intraguild predation (IGP) is common in communities, yet theory suggests it
      should not often persist and coexistence of participating species should be rare.
      As parasitism can play keystone roles in interactions between competitors, and
      between predators and prey, here we examine the role of parasites in maintaining
      IGP. We used numerical exploration of population dynamic equations to determine
      coexistence and exclusion zones for two species engaged in IGP with shared
      parasitism. We demonstrate that parasitism increases the range of conditions
      leading to coexistence when the parasite exerts a greater deleterious effect on
      the 'stronger' species in terms of the combined effects of competition and
      predation. Such a parasite can enable an inferior competitor that is also the
      less predatory to persist, and may actually lead to numerical dominance of this
      species.

PMID- 18611841
TI  - The colour of fossil feathers.
AB  - Feathers are complex integumentary appendages of birds and some other theropod
      dinosaurs. They are frequently coloured and function in camouflage and display.
      Previous investigations have concluded that fossil feathers are preserved as
      carbonized traces composed of feather-degrading bacteria. Here, an investigation
      of a colour-banded feather from the Lower Cretaceous Crato Formation of Brazil
      revealed that the dark bands are preserved as elongate, oblate carbonaceous
      bodies 1-2 microm long, whereas the light bands retain only relief traces on the
      rock matrix. Energy dispersive X-ray analysis showed that the dark bands preserve
      a substantial amount of carbon, whereas the light bands show no carbon residue.
      Comparison of these oblate fossil bodies with the structure of black feathers
      from a living bird indicates that they are the eumelanin-containing melanosomes.
      We conclude that most fossil feathers are preserved as melanosomes, and that the
      distribution of these structures in fossil feathers can preserve the colour
      pattern in the original feather. The discovery of preserved melanosomes opens up
      the possibility of interpreting the colour of extinct birds and other dinosaurs.

PMID- 18611842
TI  - Ecology and evolution join forces to good effect.
AB  - The 3rd regular meeting of the Canadian Society of Ecology and Evolution was held
      at the University of British Columbia, Vancouver, Canada from 11 to 14 May 2008.

PMID- 18611843
TI  - Mathematical models of energy homeostasis.
AB  - Diabetes and obesity present a mounting global challenge. Clinicians are
      increasingly turning to mechanism-based mathematical models for a quantitative
      definition of physiological defects such as insulin resistance, glucose
      intolerance and elevated obesity set points, and for predictions of the likely
      outcomes of therapeutic interventions. However, a very large range of such models
      is available, making a judicious choice difficult. To better inform this choice,
      here we present the most important models published to date in a uniform format,
      discussing similarities and differences in terms of the decisions faced by
      modellers. We review models for glucostasis, based on the glucose-insulin
      feedback control loop, and consider extensions to long-term energy balance,
      dislipidaemia and obesity.

PMID- 18611845
TI  - Does a 'turbophoretic' effect account for layer concentrations of insects
      migrating in the stable night-time atmosphere?
AB  - Large migrating insects, such as noctuid moths and acridoid grasshoppers, flying
      within the stable nocturnal boundary layer commonly become concentrated into
      horizontal layers. These layers frequently occur near the top of the surface
      temperature inversion where warm fast-moving airflows provide good conditions for
      downwind migration. On some occasions, a layer may coincide with a higher
      altitude temperature maximum such as a subsidence inversion, while on others, it
      may seem unrelated to any obvious feature in the vertical profile of
      meteorological variables. Insects within the layers are frequently orientated,
      either downwind or at an angle to the wind, but the mechanisms involved in both
      layer formation and common orientation have remained elusive. Here, we show
      through the results of numerical simulations that if insects are treated as
      neutrally buoyant particles, they tend to be advected by vertical gusts (through
      the 'turbophoretic' mechanism) into layers in the atmosphere where the turbulent
      kinetic energy has local minima. These locations typically coincide with local
      maxima in the wind speed and/or air temperature, and they may also provide cues
      for orientation. However, the degree of layering predicted by this model is very
      much weaker than that observed in the field. We have therefore hypothesized that
      insects behave in a way that amplifies the turbophoretic effect by initiating
      climbs or descents in response to vertical gusts. New simulations incorporating
      this behaviour demonstrated the formation of layers that closely mimic field
      observations, both in the degree of concentration in layers and the rate at which
      they form.

PMID- 18611846
TI  - Hysteresis of soft joints embedded with fluid-filled microchannels.
AB  - Many arthropods are known to achieve dynamic stability during rapid locomotion on
      rough terrains despite the absence of an elaborate nervous system. While muscle
      viscoelasticity and its inherent friction have been thought to cause this passive
      absorption of energy, the role of embedded microstructures in muscles and muscle
      joints has not yet been investigated. Inspired by the soft and flexible hinge
      joints present in many of these animals, we have carried out displacement
      controlled bending of thin elastic slabs embedded with fluid-filled
      microchannels. During loading, the slab bends uniformly to a critical curvature,
      beyond which the skin covering the channel buckles with a catastrophic decrease
      in load. In the reverse cycle, the buckled skin straightens out but at a
      significantly lower load. In such a loading-unloading cycle, this localized
      buckling phenomenon results in a dynamic change in the geometry of the joint,
      which leads to a significant hysteresis in elastic energy. The hysteresis varies
      nonlinearly with channel diameters and thicknesses of the slab, which is captured
      by a simple scaling analysis of the phenomenon.

PMID- 18611844
TI  - Biomolecular simulation and modelling: status, progress and prospects.
AB  - Molecular simulation is increasingly demonstrating its practical value in the
      investigation of biological systems. Computational modelling of biomolecular
      systems is an exciting and rapidly developing area, which is expanding
      significantly in scope. A range of simulation methods has been developed that can
      be applied to study a wide variety of problems in structural biology and at the
      interfaces between physics, chemistry and biology. Here, we give an overview of
      methods and some recent developments in atomistic biomolecular simulation. Some
      recent applications and theoretical developments are highlighted.

PMID- 18611847
TI  - Adaptive numerical competency in a food-hoarding songbird.
AB  - Most animals can distinguish between small quantities (less than four) innately.
      Many animals can also distinguish between larger quantities after extensive
      training. However, the adaptive significance of numerical discriminations in wild
      animals is almost completely unknown. We conducted a series of experiments to
      test whether a food-hoarding songbird, the New Zealand robin Petroica australis,
      uses numerical judgements when retrieving and pilfering cached food. Different
      numbers of mealworms were presented sequentially to wild birds in a pair of
      artificial cache sites, which were then obscured from view. Robins frequently
      chose the site containing more prey, and the accuracy of their number
      discriminations declined linearly with the total number of prey concealed, rising
      above-chance expectations in trials containing up to 12 prey items. A series of
      complementary experiments showed that these results could not be explained by
      time, volume, orientation, order or sensory confounds. Lastly, a violation of
      expectancy experiment, in which birds were allowed to retrieve a fraction of the
      prey they were originally offered, showed that birds searched for longer when
      they expected to retrieve more prey. Overall results indicate that New Zealand
      robins use a sophisticated numerical sense to retrieve and pilfer stored food,
      thus providing a critical link in understanding the evolution of numerical
      competency.

PMID- 18611848
TI  - Bidirectional sex change in mushroom stony corals.
AB  - Sex change occurs when an individual changes from one functional sex to another.
      The direction of sex change occurs mainly from male to female (protandry) or vice
      versa (protogyny), but sometimes may be bidirectional (repetitive). Here, for the
      first time in stony corals, we report on a protandrous sex change exhibited by
      two mushroom corals, Fungia repanda and Ctenactis echinata, with the latter also
      exhibiting bidirectional sex change. Compared with C. echinata, F. repanda
      exhibited relatively earlier sex change, significantly slower growth and higher
      mortality rates, in accordance with sex-allocation theory. Sex ratio in both the
      species was biased towards the first sex. The bidirectional sex change displayed
      by C. echinata greatly resembles that of dioecious plants that display labile
      sexuality in response to energetic and/or environmental constraints. We posit
      that, similar to these plants, in the studied corals, sex change increases their
      overall fitness, reinforcing the important role of reproductive plasticity in
      scleractinian corals in determining their evolutionary success.

PMID- 18611849
TI  - Density-dependent diversification in North American wood warblers.
AB  - Evidence from both molecular phylogenies and the fossil record suggests that
      rates of species diversification often decline through time during evolutionary
      radiations. One proposed explanation for this pattern is ecological opportunity,
      whereby an initial abundance of resources and lack of potential competitors
      facilitate rapid diversification. This model predicts density-dependent declines
      in diversification rates, but has not been formally tested in any species-level
      radiation. Here we develop a new conceptual framework that distinguishes density
      dependence from alternative processes that also produce temporally declining
      diversification, and we demonstrate this approach using a new phylogeny of North
      American Dendroica wood warblers. We show that explosive lineage accumulation
      early in the history of this avian radiation is best explained by a density
      dependent diversification process. Our results suggest that the tempo of wood
      warbler diversification was mediated by ecological interactions among species and
      that lineage and ecological diversification in this group are coupled, as
      predicted under the ecological opportunity model.

PMID- 18611850
TI  - An ancient tripartite symbiosis of plants, ants and scale insects.
AB  - In the Asian tropics, a conspicuous radiation of Macaranga plants is inhabited by
      obligately associated Crematogaster ants tending Coccus (Coccidae) scale insects,
      forming a tripartite symbiosis. Recent phylogenetic studies have shown that the
      plants and the ants have been codiversifying over the past 16-20 million years
      (Myr). The prevalence of coccoids in ant-plant mutualisms suggest that they play
      an important role in the evolution of ant-plant symbioses. To determine whether
      the scale insects were involved in the evolutionary origin of the mutualism
      between Macaranga and Crematogaster, we constructed a cytochrome oxidase I (COI)
      gene phylogeny of the scale insects collected from myrmecophytic Macaranga and
      estimated their time of origin based on a COI molecular clock. The minimum age of
      the associated Coccus was estimated to be half that of the ants, at 7-9Myr,
      suggesting that they were latecomers in the evolutionary history of the
      symbiosis. Crematogaster mitochondrial DNA (mtDNA) lineages did not exhibit
      specificity towards Coccus mtDNA lineages, and the latter was not found to be
      specific towards Macaranga taxa, suggesting that patterns of associations in the
      scale insects are dictated by opportunity rather than by specialized adaptations
      to host plant traits.

PMID- 18611851
TI  - Life history constrains biochemical development in the highly specialized
      odontocete echolocation system.
AB  - The vertebrate head has undergone enormous modification from the features borne
      by early ancestors. The growth of skull bones has been well studied in many
      species, yet little is known about corresponding soft tissue development. Among
      mammals, some of the most unusual examples of cranial evolution exist in the
      toothed whales (odontocetes). Specialized fat bodies in toothed whale heads play
      important roles in sound transmission and reception. These fat bodies contain
      unique endogenous lipids, with favourable acoustic properties, arranged in highly
      organized, three-dimensional patterns. We link variation in developmental rates
      of acoustic fats with life-history strategy, using bottlenose dolphins and
      harbour porpoises. Porpoise acoustic fats attain adult configurations earlier
      (less than 1 year) and at a faster pace than dolphins. The accelerated lipid
      accumulation in porpoises reflects the earlier need for fully functional
      echolocation systems. Dolphins enjoy 3-6 years of maternal care; porpoises must
      achieve total independence by approximately nine months. Further, a stereotypic
      'blueprint' for the spatial distribution of lipids is established prior to birth,
      demonstrating the highly conserved nature of the intricate biochemical
      arrangement in acoustic tissues. This system illustrates an unusual case of soft
      tissue development being constrained by life history, rather than the more
      commonly observed mechanistic or phyletic constraints.

PMID- 18611852
TI  - Mammalian choices: combining fast-but-inaccurate and slow-but-accurate decision
      making systems.
AB  - Empirical findings suggest that the mammalian brain has two decision-making
      systems that act at different speeds. We represent the faster system using
      standard signal detection theory. We represent the slower (but more accurate)
      cortical system as the integration of sensory evidence over time until a certain
      level of confidence is reached. We then consider how two such systems should be
      combined optimally for a range of information linkage mechanisms. We conclude
      with some performance predictions that will hold if our representation is
      realistic.

PMID- 18611853
TI  - Cytosolic and plastoglobule-targeted carotenoid dioxygenases from Crocus sativus
      are both involved in beta-ionone release.
AB  - Saffron, the processed stigma of Crocus sativus, is characterized by the presence
      of several apocarotenoids that contribute to the color, flavor, and aroma of the
      spice. However, little is known about the synthesis of aroma compounds during the
      development of the C. sativus stigma. The developing stigma is nearly odorless,
      but before and at anthesis, the aromatic compound beta-ionone becomes the
      principal norisoprenoid volatile in the stigma. In this study, four carotenoid
      cleavage dioxygenase (CCD) genes, CsCCD1a, CsCCD1b, CsCCD4a, and CsCCD4b, were
      isolated from C. sativus. Expression analysis showed that CsCCD1a was
      constitutively expressed, CsCCD1b was unique to the stigma tissue, but only
      CsCCD4a and -b had expression patterns consistent with the highest levels of beta
      carotene and emission of beta-ionone derived during the stigma development. The
      CsCCD4 enzymes were localized in plastids and more specifically were present in
      the plastoglobules. The enzymatic activities of CsCCD1a, CsCCD1b, and CsCCD4
      enzymes were determined by Escherichia coli expression, and subsequent analysis
      of the volatile products was generated by GC/MS. The four CCDs fell in two
      phylogenetically divergent dioxygenase classes, but all could cleave beta
      carotene at the 9,10(9',10') positions to yield beta-ionone. The data obtained
      suggest that all four C. sativus CCD enzymes may contribute in different ways to
      the production of beta-ionone. In addition, the location and precise timing of
      beta-ionone synthesis, together with its known activity as a fragrance and insect
      attractant, suggest that this volatile may have a role in Crocus pollination.

PMID- 18611854
TI  - The proteoglycan brevican binds to fibronectin after proteolytic cleavage and
      promotes glioma cell motility.
AB  - The adult neural parenchyma contains a distinctive extracellular matrix that acts
      as a barrier to cell and neurite motility. Nonneural tumors that metastasize to
      the central nervous system almost never infiltrate it and instead displace the
      neural tissue as they grow. In contrast, invasive gliomas disrupt the
      extracellular matrix and disperse within the neural tissue. A major inhibitory
      component of the neural matrix is the lectican family of chondroitin sulfate
      proteoglycans, of which brevican is the most abundant member in the adult brain.
      Interestingly, brevican is also highly up-regulated in gliomas and promotes
      glioma dispersion by unknown mechanisms. Here we show that brevican secreted by
      glioma cells enhances cell adhesion and motility only after proteolytic cleavage.
      At the molecular level, brevican promotes epidermal growth factor receptor
      activation, increases the expression of cell adhesion molecules, and promotes the
      secretion of fibronectin and accumulation of fibronectin microfibrils on the cell
      surface. Moreover, the N-terminal cleavage product of brevican, but not the full
      length protein, associates with fibronectin in cultured cells and in surgical
      samples of glioma. Taken together, our results provide the first evidence of the
      cellular and molecular mechanisms that may underlie the motility-promoting role
      of brevican in primary brain tumors. In addition, these results underscore the
      important functional implications of brevican processing in glioma progression.

PMID- 18611855
TI  - Cib2 binds integrin alpha7Bbeta1D and is reduced in laminin alpha2 chain
      deficient muscular dystrophy.
AB  - Mutations in the gene encoding laminin alpha2 chain cause congenital muscular
      dystrophy type 1A. In skeletal muscle, laminin alpha2 chain binds at least two
      receptor complexes: the dystrophin-glycoprotein complex and integrin alpha7beta1.
      To gain insight into the molecular mechanisms underlying this disorder, we
      performed gene expression profiling of laminin alpha2 chain-deficient mouse limb
      muscle. One of the down-regulated genes encodes a protein called Cib2 (calcium-
      and integrin-binding protein 2) whose expression and function is unknown.
      However, the closely related Cib1 has been reported to bind integrin alphaIIb and
      may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel
      integrin alpha7beta1-binding protein in muscle, we have studied Cib2 expression
      in the developing and adult mouse. Cib2 mRNA is mainly expressed in the
      developing central nervous system and in developing and adult skeletal muscle. In
      skeletal muscle, Cib2 colocalizes with the integrin alpha7B subunit at the
      sarcolemma and at the neuromuscular and myotendinous junctions. Finally, we
      demonstrate that Cib2 is a calcium-binding protein that interacts with integrin
      alpha7Bbeta1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector
      of integrin alpha7Bbeta1D signaling in skeletal muscle.

PMID- 18611856
TI  - Evidence that two enzyme-derived histidine ligands are sufficient for iron
      binding and catalysis by factor inhibiting HIF (FIH).
AB  - A 2-His-1-carboxylate triad of iron binding residues is present in many non-heme
      iron oxygenases including the Fe(II) and 2-oxoglutarate (2OG)-dependent
      dioxygenases. Three variants (D201A, D201E, and D201G) of the iron binding Asp
      201 residue of an asparaginyl hydroxylase, factor inhibiting HIF (FIH), were made
      and analyzed. FIH-D201A and FIH-D201E did not catalyze asparaginyl hydroxylation,
      but in the presence of a reducing agent, they displayed enhanced 2OG turnover
      when compared with wild-type FIH. Turnover of 2OG by FIH-D201A was significantly
      stimulated by the addition of HIF-1alpha(786-826) peptide. Like FIH-D201A and
      D201E, the D201G variant enhanced 2OG turnover but rather unexpectedly catalyzed
      asparaginyl hydroxylation. Crystal structures of the FIH-D201A and D201G variants
      in complex with Fe(II)/Zn(II), 2OG, and HIF-1alpha(786-826/788-806) implied that
      only two FIH-based residues (His-199 and His-279) are required for metal binding.
      The results indicate that variation of 2OG-dependent dioxygenase iron-ligating
      residues as a means of functional assignment should be treated with caution. The
      results are of mechanistic interest in the light of recent biochemical and
      structural analyses of non-heme iron and 2OG-dependent halogenases that are
      similar to the FIH-D201A/G variants in that they use only two His-residues to
      ligate iron.

PMID- 18611858
TI  - Ribosome performance is enhanced by a rich cluster of pseudouridines in the A
      site finger region of the large subunit.
AB  - The large subunit rRNA in eukaryotes contains an unusually dense cluster of 8-10
      pseudouridine (Psi) modifications located in a three-helix structure (H37-H39)
      implicated in several functions. This region is dominated by a long flexible
      helix (H38) known as the "A-site finger" (ASF). The ASF protrudes from the large
      subunit just above the A-site of tRNA binding, interacts with 5 S rRNA and tRNA,
      and through the terminal loop, forms a bridge (B1a) with the small subunit. In
      yeast, the three-helix domain contains 10 Psis and 6 are concentrated in the ASF
      helix (3 of the ASF Psis are conserved among eukaryotes). Here, we show by
      genetic depletion analysis that the Psis in the ASF helix and adjoining helices
      are not crucial for cell viability; however, their presence notably enhances
      ribosome fitness. Depleting different combinations of Psis suggest that the
      modification pattern is important and revealed that loss of multiple Psis
      negatively influences ribosome performance. The effects observed include slower
      cell growth (reduced rates up to 23% at 30 degrees C and 40-50% at 37 degrees C
      and 11 degrees C), reduced level of the large subunit (up to 17%), impaired
      polysome formation (appearance of half-mers), reduced translation activity (up to
      20% at 30 degrees C and 25% at 11 degrees C), and increased sensitivity to
      ribosome-based drugs. The results indicate that the Psis in the three-helix
      region improve fitness of a eukaryotic ribosome.

PMID- 18611857
TI  - Complex I within oxidatively stressed bovine heart mitochondria is
      glutathionylated on Cys-531 and Cys-704 of the 75-kDa subunit: potential role of
      CYS residues in decreasing oxidative damage.
AB  - Complex I has reactive thiols on its surface that interact with the mitochondrial
      glutathione pool and are implicated in oxidative damage in many pathologies.
      However, the Cys residues and the thiol modifications involved are not known.
      Here we investigate complex I thiol modification within oxidatively stressed
      mammalian mitochondria, containing physiological levels of glutathione and
      glutaredoxin 2. In mitochondria incubated with the thiol oxidant diamide, complex
      I is only glutathionylated on the 75-kDa subunit. Of the 17 Cys residues on the
      75-kDa subunit, 6 are not involved in iron-sulfur centers, making them plausible
      candidates for glutathionylation. Mass spectrometry of complex I from oxidatively
      stressed bovine heart mitochondria showed that only Cys-531 and Cys-704 were
      glutathionylated. The other four non-iron-sulfur center Cys residues remained as
      free thiols. Complex I glutathionylation also occurred in response to relatively
      mild oxidative stress caused by increased superoxide production from the
      respiratory chain. Although complex I glutathionylation within oxidatively
      stressed mitochondria correlated with loss of activity, it did not increase
      superoxide formation, and reversal of glutathionylation did not restore complex I
      activity. Comparison with the known structure of the 75-kDa ortholog Nqo3 from
      Thermus thermophilus complex I suggested that Cys-531 and Cys-704 are on the
      surface of mammalian complex I, exposed to the mitochondrial glutathione pool.
      These findings suggest that Cys-531 and Cys-704 may be important in preventing
      oxidative damage to complex I by reacting with free radicals and other damaging
      species, with subsequent glutathionylation recycling the thiyl radicals and
      sulfenic acids formed on the Cys residues back to free thiols.

PMID- 18611859
TI  - Lxralpha deficiency hampers the hepatic adaptive response to fasting in mice.
AB  - Besides its well established role in control of cellular cholesterol homeostasis,
      the liver X receptor (LXR) has been implicated in the regulation of hepatic
      gluconeogenesis. We investigated the role of the major hepatic LXR isoform in
      hepatic glucose metabolism during the feeding-to-fasting transition in vivo. In
      addition, we explored hepatic glucose sensing by LXR during carbohydrate
      refeeding. Lxralpha(-/-) mice and their wild-type littermates were subjected to a
      fasting-refeeding protocol and hepatic carbohydrate fluxes as well as whole body
      insulin sensitivity were determined in vivo by stable isotope procedures.
      Lxralpha(-/-) mice showed an impaired response to fasting in terms of hepatic
      glycogen depletion and triglyceride accumulation. Hepatic glucose 6-phosphate
      turnover was reduced in 9-h fasted Lxralpha(-/-) mice as compared with controls.
      Although hepatic gluconeogenic gene expression was increased in 9-h fasted
      Lxralpha(-/-) mice compared with wild-type controls, the actual gluconeogenic
      flux was not affected by Lxralpha deficiency. Hepatic and peripheral insulin
      sensitivity were similar in Lxralpha(-/-) and wild-type mice. Compared with wild
      type controls, the induction of hepatic lipogenic gene expression was blunted in
      carbohydrate-refed Lxralpha(-/-) mice, which was associated with lower plasma
      triglyceride concentrations. Yet, expression of "classic" LXR target genes Abca1,
      Abcg5, and Abcg8 was not affected by Lxralpha deficiency in carbohydrate-refed
      mice. In summary, these studies identify LXRalpha as a physiologically relevant
      mediator of the hepatic response to fasting. However, the data do not support a
      role for LXR in hepatic glucose sensing.

PMID- 18611860
TI  - CCL2 protects prostate cancer PC3 cells from autophagic death via
      phosphatidylinositol 3-kinase/AKT-dependent survivin up-regulation.
AB  - Resistance to cell death is a hallmark of cancer. Autophagy is a survival
      mechanism activated in response to nutrient deprivation; however, excessive
      autophagy will ultimately induce cell death in a nonapoptotic manner. The present
      study demonstrates that CCL2 protects prostate cancer PC3 cells from autophagic
      death, allowing prolonged survival in serum-free conditions. Upon serum
      starvation, CCL2 induced survivin up-regulation in PC3, DU 145, and C4-2B
      prostate cancer cells. Both cell survival and survivin expression were stunted in
      CCL2-stimulated PC3 cells when treated either with the phosphatidylinositol 3
      kinase inhibitor LY294002 (2 microm) or the Akt-specific inhibitor-X (Akti-X; 2.5
      microm). Furthermore, CCL2 significantly reduced light chain 3-II (LC3-II) in
      serum-starved PC3; in contrast, treatment with LY294002 or Akti-X reversed the
      effect of CCL2 on LC3-II levels, suggesting that CCL2 signaling limits autophagy
      in these cells. Upon serum deprivation, the analysis of LC3 localization by
      immunofluorescence revealed a remarkable reduction in LC3 punctate after CCL2
      stimulation. CCL2 treatment also resulted in a higher sustained mTORC1 activity
      as measured by an increase in phospho-p70S6 kinase (Thr389). Rapamycin, an
      inducer of autophagy, both down-regulated survivin and decreased PC3 cell
      viability in serum-deprived conditions. Treatment with CCL2, however, allowed
      cells to partially resist rapamycin-induced death, which correlated with survivin
      protein levels. In two stable transfectants expressing survivin-specific short
      hairpin RNA, generated from PC3, survivin protein levels controlled both cell
      viability and LC3 localization in response to CCL2 treatment. Altogether, these
      findings indicate that CCL2 protects prostate cancer PC3 cells from autophagic
      death via the phosphatidylinositol 3-kinase/Akt/survivin pathway and reveal
      survivin as a critical molecule in this survival mechanism.

PMID- 18611861
TI  - Inhibition of cortical neuron differentiation by Groucho/TLE1 requires
      interaction with WRPW, but not Eh1, repressor peptides.
AB  - In both invertebrates and vertebrates, transcriptional co-repressors of the
      Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate a number of
      developmental mechanisms, including neuronal differentiation. The pleiotropic
      activity of Gro/TLE depends on context-specific interactions with a variety of
      DNA-binding proteins. Most of those factors engage Gro/TLE through two different
      types of short peptide motifs, the WRP(W/Y) tetrapeptide and the Engrailed
      homology 1 (Eh1) sequence (FXIXXIL). The aim of this study was to elucidate the
      contribution of WRP(W/Y) and Eh1 motifs to mammalian Gro/TLE anti-neurogenic
      activity. Here we describe point mutations within the C-terminal WD40 repeat
      domain of Gro/TLE1 that do not perturb protein folding but disrupt the ability of
      Gro/TLE1 to inhibit the differentiation of cerebral cortex neural progenitor
      cells into neurons. One of those mutations, L743F, selectively blocks binding to
      Hes1, an anti-neurogenic basic helix-loop-helix protein that harbors a WRPW
      motif. In contrast, the L743F mutation does not disrupt binding to Engrailed1 and
      FoxG1, which both contain Eh1 motifs, nor to Tcf3, which binds to the Gro/TLE N
      terminus. These results demonstrate that the recruitment of transcription factors
      harboring WRP(W/Y) tetrapeptides is essential to the anti-neurogenic function of
      Gro/TLE1.

PMID- 18611862
TI  - Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast
      cancer cells.
AB  - SLIT-2 is considered as a candidate tumor suppressor gene, because it is
      frequently inactivated in various cancers due to hypermethylation of its promoter
      region and allelic loss. However, the exact mechanism of its tumor-suppressive
      effect has not been elucidated. Here, we observed that Slit-2-overexpressing
      breast cancer cells exhibited decreased proliferation and migration capabilities
      compared with control cells under in vitro conditions. These results were
      confirmed in vivo in mouse model systems. Mice injected with MCF-7/Slit-2 cells
      showed a 60-70% reduction in tumor size compared with mice injected with MCF-7/VC
      cells both in the absence and presence of estrogen. Upon further elucidation, we
      observed that Slit-2 mediates the tumor-suppressive effect via a coordinated
      regulation of the beta-catenin and PI3K signaling pathways and by enhancing beta
      catenin/E-cadherin-mediated cell-cell adhesion. Our study for the first time
      reveals that Slit-2-overexpressing breast cancer cells exhibit tumor suppressor
      capabilities through the novel mechanism of beta-catenin modulation.

PMID- 18611864
TI  - Sunitinib in the treatment of tubulocystic carcinoma of the kidney. A case
      report.

PMID- 18611863
TI  - The gregarious lipid droplet.

PMID- 18611865
TI  - The treatment of advanced gastric cancer: current strategies and future
      perspectives.

PMID- 18611866
TI  - Pathology: is it still necessary?

PMID- 18611867
TI  - Preoperative therapy: what, when and for whom?

PMID- 18611868
TI  - Progress in radiotherapy for early breast cancer.

PMID- 18611869
TI  - Recent advances in adjuvant systemic therapy for early-stage breast cancer.

PMID- 18611895
TI  - Long-term survivorship after cancer: how far have we come?

PMID- 18611896
TI  - Biomarkers in drug development.

PMID- 18611897
TI  - Cancer and pregnancy.

PMID- 18611898
TI  - Cancer stem cells.

PMID- 18611899
TI  - Translating genetic pathways to protein networks for cancer sub-typing.

PMID- 18611900
TI  - HPV vaccines and cervical cancer.

PMID- 18611901
TI  - Nutritional issues in anti-cancer treatment.

PMID- 18611902
TI  - New insights into molecular mechanisms of haematological malignancies.

PMID- 18611903
TI  - Recent therapeutic advances in hematological malignancies: the role of targeted
      therapies in lymphoma.

PMID- 18611904
TI  - New treatments in multiple myeloma: beyond optimal treatment.

PMID- 18611905
TI  - Recent therapeutic advances in hematological malignancies: dealing with treatment
      related complications.

PMID- 18611906
TI  - Genetic counseling: what is important to know in your clinic.

PMID- 18611907
TI  - The clinical implications of genetics. BRCA1- and BRCA2-positive: how do I
      proceed? Implications for ovarian cancer prevention.

PMID- 18611908
TI  - The implications of genetics in colorectal cancer.

PMID- 18611909
TI  - Current role of surgery and multimodal treatment in localized gastric cancer.

PMID- 18611910
TI  - Perioperative or postoperative therapy for resectable gastric cancer?

PMID- 18611911
TI  - A novel activator-type ERF of Thinopyrum intermedium, TiERF1, positively
      regulates defence responses.
AB  - Thinopyrum intermedium is resistant to many different pathogens. To understand
      the roles of ethylene response factors (ERFs) in defence responses, the first
      member of the ERF family in T. intermedium, TiERF1, was characterized and
      functionally analysed in this study. The TiERF1 gene encodes a putative protein
      of 292 amino acids, belonging to the B3 subgroup of the ERF transcription factor
      family. Biochemical assays demonstrated that the TiERF1 protein is capable of
      binding to the GCC box, a cis-element present in the promoters of pathogenesis
      related (PR) genes, and possessing transactivation activity, as well as
      localizing to the nucleus. The transcript of TiERF1 in T. intermedium is rapidly
      induced by infection with Rhizoctonia cerealis, Fusarium graminearum, or Blumeria
      graminis, and ethylene, jasmonic acid, and salicylic acid treatments. More
      importantly, the ectopic expression of TiERF1 in tobacco activated the transcript
      of the PR genes of tobacco with a GCC box cis-element, and ACO and ACS genes key
      to ethylene synthesis, and in turn improved the resistance level to Alternaria
      alternata and tobacco mosaic virus, as well as causing some phenotypic changes
      associated with ethylene response in the transgenic tobacco plants. Taken
      together, TiERF1 protein as an ERF transcription activator positively regulates
      defence responses via the activation of some defence-related genes.

PMID- 18611912
TI  - Difference in metabolite levels between photoautotrophic and photomixotrophic
      cultures of Synechocystis sp. PCC 6803 examined by capillary electrophoresis
      electrospray ionization mass spectrometry.
AB  - Capillary electrophoresis mass spectrometry (CE/MS) was applied for the
      comprehensive survey of changes in the amounts of metabolites upon the shift from
      photoautotrophic to photomixotrophic conditions in Synechocystis sp. PCC 6803.
      When glucose was added to the photoautotrophically grown culture, the increase in
      the metabolites for the oxidative pentose phosphate (OPP) pathway and glycolysis,
      together with the decrease in those for the Calvin cycle, was observed.
      Concomitantly, the increase in respiratory activity and the decrease in
      photosynthetic activity took place in the wild-type cells. In the pmgA-disrupted
      mutant that shows growth inhibition under photomixotrophic conditions, lower
      enzymatic activities of the OPP pathway and higher photosynthetic activity were
      observed, irrespective of trophic conditions. These defects brought about
      metabolic disorders such as a decrease in ATP and NADPH contents, a failure in
      the activation of respiratory activity, and the aberrant accumulation of
      isocitrate under photomixotrophic but not under photoautotrophic conditions. A
      delicate balancing of the carbon flow between the Calvin cycle and the OPP
      pathway seems indispensable for growth specifically under photomixotrophic
      conditions and PmgA is likely to be involved in the regulation.

PMID- 18611913
TI  - Generation and homogeneity of aerosols in a human whole-body inhalation chamber.
AB  - INTRODUCTION: A 16 m(3) whole-body exposure chamber for human exposure to
      aerosols is described. Several modifications of the aerosol generation and
      distribution system were needed to ensure a stable aerosol concentration in the
      chamber, especially when a cyclone pre-classifier was used. RESULTS: After these
      modifications, stable aerosol concentrations of aluminium oxide with a volume
      median diameter of 5.7 microm, and approximately 3 microm when the cyclone was
      used, could be achieved after 1 h of aerosol generation. Aerosol concentrations
      of 1-8 mg m(-3) generated without the cyclone could be maintained for at least 2
      h after the aerosol level had stabilized. The temporal variability [coefficient
      of variation (CV)] of the aerosol concentration was 4-6%, while concentrations <1
      mg m(-3) showed greater relative variability. The spatial variability at 3.8 mg
      m(-3) without a volunteer in the chamber was 4.8%. With a volunteer in the
      chamber who performed 30 min of ergometric cycling during 2 h of aerosol
      exposure, the exposure estimated by personal sampling was 15-17% lower than
      monitored with an optical particle counter. The variability of personally
      measured exposure was higher than of stationary measurements showing CVs of 10
      19%. CONCLUSIONS: These results show that controlled exposure of human volunteers
      to a range of concentrations can be achieved with good accuracy in this
      inhalation chamber. The results compare favourably with other chambers described
      in the literature. Personal sampling showed lower aerosol concentrations than
      estimated in an empty chamber and the variability was significantly higher than
      measured stationary.

PMID- 18611914
TI  - The determinants of dermal exposure ranking method (DERM): a pesticide exposure
      assessment approach for developing countries.
AB  - A new method for assessment of dermal exposure to pesticides in subsistence
      farmers by use of determinants of dermal exposure is described. The method,
      called the determinants of dermal exposure ranking method (DERM), is a
      combination of checklists and expert rating assessment. Thus, determinants are
      listed in a form, which is used to check their presence and to assess them using
      a simple algorithm based on two factors, the type of transport process (T value)
      and the area of body surface exposed (A value). In addition, the type of clothing
      worn during applications is included as a protection factor. We applied the DERM
      to real pesticide applications, characterizing dermal exposure and comparing DERM
      estimates with earlier developed semiquantitative visual scores based on
      fluorescent tracer, the total visual score (TVS) and contaminated body area
      (CBA). DERM showed a very good level of agreement with both the TVS (r = 0.69; P
      = 0.000) and the CBA (r = 0.67; P = 0.000). DERM allowed identification of the
      determinants that had the highest effect on exposure and the farmers with the
      highest exposure. In conclusion, DERM provided information on the determinants
      responsible for dermal exposure in a group of subsistence farmers. This can be
      useful to design monitoring and preventive programs, define priorities for
      intervention and prioritize and select most adequate measurement strategies. DERM
      promises to be a low-cost easy-to-use method to assess dermal exposure to
      pesticides in developing country conditions.

PMID- 18611915
TI  - Effect of prophylactic 5-HT3 receptor antagonists on pruritus induced by
      neuraxial opioids: a quantitative systematic review.
AB  - Pruritus is a frequent adverse event observed after neuraxial administration of
      opioids. Central 5-hydroxytryptamine subtype 3 (5-HT3) receptors may be activated
      in this process. This systematic review aimed to evaluate the efficacy of
      prophylactic 5-HT3 receptor antagonists on neuraxial opioid-induced pruritus. We
      searched Medline, Embase, and Cochrane Collaboration Library databases. Studies
      were evaluated with the Oxford Validity Scale. Studies with a score of 3 or more
      and reporting prophylactic administration of 5-HT3 receptor antagonists vs
      placebo were included. Fifteen randomized double-blind controlled trials (n=1337)
      were selected. 5-HT3 antagonists (n=775) significantly reduced pruritus [odds
      ratio (OR) 0.44 (95% confidence interval, 95% CI, 0.29-0.68), P=0.0002, number
      needed-to-treat (NNT) 6 (95% CI, 4-14)], the treatment request for pruritus [OR
      0.58 (95% CI, 0.43-0.78), P=0.0003, NNT 10 (95% CI, 7-20)], the intensity of
      pruritus [weighted mean difference (WMD) -0.35 (95% CI, -0.59 to -0.10),
      P=0.007], the incidence and the intensity of postoperative nausea and vomiting
      (PONV), and the need of rescue treatment [respectively, Peto odds ratio (Peto OR)
      0.43 (95% CI, 0.31-0.58), P<0.00001, NNT 7 (95% CI, 6-10); WMD -0.12 (95% CI, 
      0.24 to 0.00), P=0.05 and OR 0.42 (95% CI, 0.20-0.86), P=0.02, NNT 8 (95% CI, 5
      35)]. However, the funnel plot was asymmetric, suggesting a risk of publication
      bias. 5-HT3 receptor antagonists may be an effective strategy in preventing
      neuraxial opioid-induced pruritus and PONV. Further large randomized controlled
      trials are required to confirm these findings.

PMID- 18611916
TI  - Transgenic cyclooxygenase-2 expression and high salt enhanced susceptibility to
      chemical-induced gastric cancer development in mice.
AB  - Cyclooxoygenase (COX)-2 overexpression is involved in gastric carcinogenesis.
      While high-salt intake is a known risk factor for gastric cancer development, we
      determined the effects of high salt on gastric chemical carcinogenesis in COX-2
      transgenic (TG) mice. COX-2 TG mice were developed in C57/BL6 strain using the
      full-length human cox-2 complementary DNA construct. Six-week-old COX-2 TG and
      wild-type (WT) littermates were randomly allocated to receive alternate week of N
      methyl-N-nitrosourea (MNU, 240 p.p.m.) in drinking water or control for 10 weeks.
      Two groups of mice were further treated with 10% NaCl during the initial 10
      weeks. All mice were killed at the end of week 50. Both forced COX-2
      overexpression and high-salt intake significantly increased the frequency of
      gastric cancer development in mice as compared with WT littermates treated with
      MNU alone. However, no additive effect was observed on the combination of high
      salt and COX-2 expression. We further showed that MNU and high-salt treatment
      increased chronic inflammatory infiltrates and induced prostaglandin E(2)
      (PGE(2)) production in the non-cancerous stomach. Whereas high-salt treatment
      markedly increased the expression of inflammatory cytokines (tumor necrosis
      factor-alpha, interferon-gamma, interleukin (IL)-1 beta and IL-6) in the gastric
      mucosa, COX-2 overexpression significantly altered the cell kinetics in the MNU
      induced gastric cancer model. In conclusion, both high salt and COX-2
      overexpression promote chemical-induced gastric carcinogenesis, possibly related
      to chronic inflammation, induction of PGE(2), disruption of cell kinetics and
      induction of inflammatory cytokines.

PMID- 18611917
TI  - Distinct GAGE and MAGE-A expression during early human development indicate
      specific roles in lineage differentiation.
AB  - BACKGROUND: Expression of cancer/testis-associated proteins (CTAs) has
      traditionally been considered to be restricted to germ cells in normal tissues
      and to different types of malignancies. We have evaluated the potential role of
      CTAs in early human development. METHODS: Using immunohistochemistry and RT-PCR,
      we investigated the expression of CTAs in differentiated human embryonic stem
      cells (hESC) and in late embryos and early fetuses. RESULTS: We found that
      melanoma antigen A (MAGE-A) family members were expressed during differentiation
      of hESC to embryoid bodies and in teratomas, and overlapped with expression of
      the neuroectodermal markers beta-tubulin 3, Pax6 and nestin. A widespread
      expression of MAGE-A was also observed in neurons of the early developing central
      nervous system and peripheral nerves. G antigen (GAGE) expression was present in
      the early ectoderm of embryos, including cells of the ectodermal ring and apical
      epidermal ridge. Neuroectodermal cells in the floor plate and adjacent processes
      and endfeet of radial glial cells also expressed GAGE. In addition, GAGE family
      members were expressed in the peripheral adrenal cortex of 6-9-week-old embryos
      and fetuses, which specifically correlated with massive cellular proliferation
      and establishment of the definitive and fetal zones. Overlapping expression of
      MAGE-A and GAGE proteins occurred in migrating primordial germ cells.
      CONCLUSIONS: Our results show that CTAs, in addition to their role in germ cells,
      may be involved in early development of various types of somatic cells, and
      suggest that they are implicated in specific differentiation processes.

PMID- 18611918
TI  - ESHRE task force on ethics and law 15: cross-border reproductive care.
AB  - This paper analyses the ethical aspects of cross-border reproductive care.
      Ethical questions are raised by some of the main reasons of cross-border
      travelling, i.e. law evasion and unequal access to treatment. The phenomenon also
      generates possible conflicts linked to the responsibility of the professionals.
      Three points are discussed: the moral obligation of the physician to refer the
      patient, his/her duty to provide information and counselling and the
      acceptability of fee-splitting. The recommendations focus on measures to reduce
      or limit the number of patients that have to travel abroad and on steps to
      guarantee the safety and quality of the treatment wherever it is provided.

PMID- 18611919
TI  - Similar biological characteristics of human embryonic stem cell lines with normal
      and abnormal karyotypes.
AB  - BACKGROUND: Human embryonic stem cell (hESC) lines derived from poor quality
      embryos usually have either normal or abnormal karyotypes. However, it is still
      unclear whether their biological characteristics are similar. METHODS: Seven new
      hESC lines were established using discarded embryos. Five cell lines had normal
      karyotype, one was with an unbalanced Robertsonian translocation and one had a
      triploid karyotype. Their biological characteristics, short tandem repeat loci,
      HLA typing, differentiation capability and imprinted gene, DNA methylation and X
      chromosome inactivation status were compared between different cell lines.
      RESULTS: All seven hESC lines had similar biological characteristics regardless
      of karyotype (five normal and two abnormal), such as expression of stage-specific
      embryonic antigen (SSEA)-4, tumor-rejection antigen (TRA)-1-81 and TRA-1-60
      proteins, transcription factor octamer binding protein 4 mRNA, no detectable
      expression of SSEA-1 protein and high levels of alkaline phosphatase activity.
      All cell lines were able to undergo differentiation. Imprinted gene expression
      and DNA methylation were also similar among these cell lines. Non-random X
      chromosome inactivation patterns were found in XX cell lines. CONCLUSIONS: The
      present results suggest that hESC lines with abnormal karyotype are also useful
      experimental materials for cell therapy, developmental biology and genetic
      research.

PMID- 18611920
TI  - The genetics of SLE: an update in the light of genome-wide association studies.
AB  - Understanding the pathogenesis of SLE remains a considerable challenge. Multiple
      abnormalities of both the innate and adaptive immune system have been described
      and, furthermore, immunological dysfunction precedes clinical presentation by
      many years. There is a strong genetic basis to SLE, which means that genetic
      studies can play a key role in furthering our understanding of this disease.
      Since susceptibility variants are present from birth and are unaffected by the
      course of the disease, or by its treatment, genetic analysis is, perhaps
      uniquely, capable of identifying fundamental, causative, disease mechanisms. Over
      the last 12 months, there has been a staggering increase in our understanding of
      SLE genetics. We have seen the identification of new and important SLE
      susceptibility genes through candidate gene studies, and we have seen the
      publication of two whole-genome association analyses. The 'hypothesis free' whole
      genome studies have provided additional evidence in support of a number of
      existing susceptibility genes and have identified novel gene candidates. In this
      article, we review the current SLE genetics literature in the light of these
      recent advances and we discuss our current understanding of the functional role
      of the key susceptibility genes. By considering how these genes fall into
      clusters with shared function we can begin to understand how dysregulation at a
      number of key immunological steps may predispose to the development of SLE.

PMID- 18611921
TI  - Safer NSAID strategies: consensus or contentious?

PMID- 18611922
TI  - Sarcoidosis and inclusion body myositis.

PMID- 18611923
TI  - An incremental step in patient safety: reducing the risks of retained foreign
      bodies by the use of an integrated laparotomy pad/retractor.
AB  - Retained foreign body is a recognized complication of abdominal, pelvic, and
      thoracic surgery and a cause of medical malpractice. Efforts to reduce its
      incidence include safe exposure and the use of fewer laparotomy pads. The EZ DASH
      is an absorbent 12-thickness laparotomy pad covering a malleable stainless steel
      mesh, providing both the needed retraction and a reduction in the use of
      individual pads. EZ DASH has been introduced into clinical use in 183 consecutive
      cases by specialty surgeons (colorectal, gynecology, and gynecologic oncology
      services) at multiple medical centers. The retractor may be shaped to the
      individual needs of an operating field, eg, the pelvis, and the small bowel
      secured behind the retractor, held in place by the tension of its mesh and the
      security of the abdominal wall. Positioning has been intuitive and secure, and
      the intraoperative use of sponges and of operating time have both been noticeably
      reduced. Among 183 cases, 91% of uses were felt to reduce OR time by <or=5 to
      >or=10 minutes. Ninety-three percent of EZ DASH cases used fewer individual
      laparotomy pads for small bowel retraction. Ninety-five percent of uses suggested
      a value added to the case by the operating surgeon with an expressed desire to
      use the product repeatedly. The EZ DASH is a simple method of obtaining small
      bowel retraction and laparotomy pad absorption with a reduction in the need for
      individual pads, providing excellent exposure for the operative field and
      reducing the risk of retained foreign body.

PMID- 18611924
TI  - The use of corticosteroids to treat keloids: a review.
AB  - Mechanisms for keloid formation include drastic changes in growth factor actions,
      collagen turnover, mechanical forces applied over the skin, and genetic and
      immunologic contributions. The use of corticosteroids to manage keloids increases
      basic fibroblast growth factor production while decreasing transforming growth
      factor-beta1 production by human dermal fibroblasts, endogenous vascular
      endothelial growth factor, and insulin-like growth factor-1. The use of
      corticosteroid injections is, to date, the core treatment available for the
      management of excessive tissue production in scars. Currently, the most effective
      and safe regimen for keloid management appears to be the use of corticotherapy
      injection of intradermal steroids after a surgical excision.

PMID- 18611925
TI  - Multilocular cystic nephroma and multicystic clear cell carcinoma: two faces of
      the Roman god Janus?

PMID- 18611926
TI  - Massive localized lymphedema with unusual presentations: report of 2 cases and
      review of the literature.
AB  - Massive localized lymphedema is a benign soft tissue lesion that usually presents
      as a large mass in morbidly obese adults. The diagnosis may be challenging as it
      can mimic other lesions, including well-differentiated liposarcoma. We report 2
      cases of massive localized lymphedema with unusual presentation. The first case
      is a recurrent massive localized lymphedema in the right thigh of a 40-year-old
      morbidly obese woman. In addition to typical massive localized lymphedema
      features such as prominent edema and vascular proliferation in the adipose
      tissue, we observed prominent and abundant multinucleated stromal floret-like
      giant cells, arborizing network of capillaries, and areas of hyalinized collagen.
      Our second case is in a rare location (scrotum extending into penile soft tissue)
      in an overweight 55-year-old male. This lesion exhibits striking smooth muscle
      hyperplasia. Lack of staining by antibodies against murine double minute 2
      protein and cyclin dependent kinase 4 and absence of high mobility group AT- hook
      2 transcription factor rearrangement by fluorescence in situ hybridization
      support our diagnosis of massive localized lymphedema in both cases.

PMID- 18611927
TI  - Histopathological aspects of neurocryptococcosis in HIV-infected patients:
      autopsy report of 45 patients.
AB  - The authors describe the histopathological necropsy findings of 45 human
      immunodeficiency virus (HIV)-infected patients with neurocryptococcosis. Systemic
      cryptococcosis with involvement of multiple organs such as spleen, liver, and
      lungs was present in all patients. Predominant diffuse meningoencephalitis
      predominantly in the basal ganglia, thalamus, and mid-brain, with minimal
      inflammatory infiltrate was seen in 30 AIDS patients (70%). We frequently
      observed in those patients the presence of multiple gelatinous pseudocysts with
      abundant Cryptococcus neoformans in the Virchow-Robin spaces and adjacent brain
      caused by the dissemination of the meningeal infection along the perivascular
      spaces. Isolated meningeal and cerebral involvement with minimal inflammatory
      infiltrate with numerous fungal organisms, and occasionally with granulomatous
      reaction and necrosis, was seen in 15 patients (30%). In addition to involvement
      of multiple organs by C. neoformans, HIV-infected patients with clinical
      manifestations of neurocryptococcosis frequently present a widespread involvement
      of the brain.

PMID- 18611929
TI  - Merits of the PMiT (papillary microtumor) terminology in the definition of a
      subset of incidental papillary microcarcinomas of the thyroid.
AB  - An exponential increase in the detection of papillary thyroid microcarcinomas
      (PTMCs) has been observed in recent times, possibly because of recent
      improvements in the management of thyroid lesions and extensive histological
      examination. However, no definitive treatment guideline has been developed for
      PTMC, resulting in patients undergoing overtreatment. In 2003, the term papillary
      microtumor of the thyroid (PMiT) was proposed for small (< or =1 cm)
      intrathyroidal tumors with excellent prognostic prospects along with strict
      definition criteria. Since then, the term PMiT has been adopted by clinicians and
      surgeons. In this article, the authors report a series of 50 consecutive cases of
      PMiT collected and treated at the University Hospital of Turin, Italy. From the
      authors' experience, this terminology, which demarks a subset of PTMC, should be
      widely adopted as it is biologically sound, well accepted by both clinicians and
      patients, decreases the danger of overtreatment, minimizes the psychological
      anxiety engendered by a diagnosis of carcinoma, and maintains the patient's
      eligibility for health insurance.

PMID- 18611928
TI  - E-selectin and Sialyl Lewis X expression is associated with lymph node metastasis
      of invasive micropapillary carcinoma of the breast.
AB  - To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X,
      in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100
      cases of invasive micropapillary carcinoma and 97 cases of invasive ductal
      carcinoma were analyzed immunohistochemically for the expression of E-selectin
      and Sialyl Lewis X, along with CD34, to measure the microvessel density of
      invasive micropapillary carcinoma. We found that the number of E-selectin
      positive vessels was greater in invasive micropapillary carcinoma than in
      invasive ductal carcinoma, and it was significantly correlated with the
      histological grade, the number of positive lymph nodes, and the microvessel
      density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of
      invasive micropapillary carcinoma was higher than that of invasive ductal
      carcinoma, which was also associated with lymph node metastasis. In invasive
      micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the
      stroma-facing surface of the cell clusters and the adjacent stroma, while in
      invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These
      findings suggested that E-selectin and Sialyl Lewis X might play an important
      role in lymph node metastasis in invasive micropapillary carcinoma. The
      expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma
      suggested that the reversal of cell polarity of invasive micropapillary carcinoma
      might be as an important factor for the morphogenesis and possibly the
      pathogenesis, especially their higher rates of lymph node metastasis.

PMID- 18611930
TI  - IgG4-positive sclerosing cholangitis following autoimmune pancreatitis with
      deranged CA19.9.
AB  - Sclerosing cholangitis is an autoimmune condition characterized by lymphocytic
      infiltration within the biliary epithelium leading to multifocal stricturing of
      the biliary tree. Primary sclerosing cholangitis (PSC) is the most common type
      encountered clinically. However, a similar process may occur in conjunction with
      autoimmune pancreatitis (AIP), known as AIP-associated sclerosing cholangitis
      (AIP-SC). This subtype is associated with an elevated IgG(4) level and the
      presence of a number of autoantibodies. AIP-SC shows good response to steroid
      treatment, distinguishing it clinically from PSC. The authors report a case of
      AIP-SC in a patient who had previously undergone a biliary bypass for AIP-induced
      chronic pancreatitis. The presentation of jaundice and grossly elevated tumor
      marker, CA19.9, raised the concern of malignancy. The uncertainty of the
      diagnosis was resolved when AIP-SC was confirmed on liver biopsy, with a
      concomitantly elevated serum IgG(4) level. The disease went into remission with
      steroid treatment.

PMID- 18611931
TI  - Primary capillary hemangioblastoma of bone: report of a case arising in the
      sacrum.
AB  - Capillary hemangioblastoma (CHB) is a benign, highly vascularized tumor that
      generally occurs in the central nervous system either in the setting of von
      Hippel-Lindau (VHL) disease or, more often, as a solitary sporadic lesion that is
      increasingly recognized in extraneural sites. We present the case of a 72-year
      old woman with low back pain and a well-demarcated lytic lesion of the sacrum,
      which at histological and ultrastructural examination was indistinguishable from
      central nervous system CHB. The patient had no signs of VHL disease and died of
      another cause with no evidence of disease 57 months after curettage of the
      lesion. To our knowledge, this is the second case of CHB reported to occur in
      bone.

PMID- 18611932
TI  - Pseudoangiomatous stromal hyperplasia (PASH) of the breast with foci of
      morphologic malignancy: a case of PASH with malignant transformation?
AB  - Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of the
      hormonally responsive, specialized mammary stroma characterized by slit-like
      pseudovascular spaces lined by bland spindle cells. It is usually an incidental
      microscopic finding but in some cases it may present as a slowly growing mass. A
      malignant counterpart for this lesion has not been reported. We describe a case
      of PASH with foci of malignant histologic features presenting as a slowly growing
      mass in a 30-year-old woman. The previously reported variants of PASH and the
      other mammary stromal lesions related to PASH are also discussed. This is perhaps
      the first case of PASH with foci of malignant histologic features reported in the
      literature and represents a rare sarcoma derived from specialized hormonally
      responsive mammary stroma.

PMID- 18611933
TI  - Aggressive osteoblastoma: a case report involving a unique chromosomal
      aberration.
AB  - Osteoblastomas are rare bone-producing neoplasms that generally occur in the
      young and can be misdiagnosed as an osteosarcoma if correlation with clinical
      history, radiology, and histology is not carefully considered or if the several
      variants of osteoblastoma are not recognized. These variants lie on a morphologic
      spectrum between conventional osteoblastoma and osteosarcoma. Aggressive
      osteoblastoma is one such subtype. As the name implies, the histologic features
      of aggressive osteoblastoma may appear malignant, and its biologic behavior may
      separate it from conventional osteoblastoma. We report a case of aggressive
      osteoblastoma occurring in the femoral diaphysis of a 12-year-old girl; this
      osetoblastoma was dyssynchronous from the radiologic appearance and a diagnostic
      challenge. Cytogenetic evaluation of the neoplasm revealed a pseudodiploid clone
      with a balanced translocation involving chromosomes 4, 7, and 14. Using the
      premise that cytogenetics might be useful as a diagnostic tool for a more
      specific classification, we reviewed the literature in order to compare our
      findings with known chromosomal aberrations.

PMID- 18611934
TI  - Starry thyroid.

PMID- 18611935
TI  - Alveolar rhabdomyosarcoma with neuroendocrine/neuronal differentiation: report of
      3 cases.
AB  - The aim of this study is to report the clinicopathologic characteristics of 3
      cases of alveolar rhabdomyosarcoma with neuroendocrine/neuronal differentiation.
      Specimens of 3 cases of alveolar rhabdomyosarcoma were studied using histologic,
      immunohistochemical, ultrastructural, and molecular genetic techniques. The
      patients were a 19-year-old man with metastatic alveolar rhabdomyosarcoma in a
      groin lymph node, a 16-year-old girl with alveolar rhabdomyosarcoma of the
      perineum, and a 20-year-old man with recurrent orbital alveolar rhabdomyosarcoma.
      Microscopically, case 1 was composed of compact sheets of medium to large tumor
      cells. Cases 2 and 3 were small blue round cell tumors. Cases 1 and 3 were solid
      throughout, whereas case 2 demonstrated alveolar and solid architecture. By
      immunohistochemistry, the following markers were positive: desmin (3/3), myogenin
      (3/3), synaptophysin (3/3), and chromogranin (2/3). Ultrastructurally, sarcomeric
      filaments were seen in all cases, while neuroendocrine granules were detected
      only in case 1. PAX:FKHR fusion transcript was identified in case 2, case 3 had a
      variant PAX3 transcript, and case 1 was negative. The data presented expands the
      known differentiation of alveolar rhabdomyosarcoma.

PMID- 18611936
TI  - Collision renal tumors.

PMID- 18611937
TI  - Myositis ossificans associated with subclinical idiopathic thrombocytopenic
      purpura: report of a case.
AB  - A 56-year-old healthy man noticed a stony-hard mass gradually grown in his neck
      for more than a 6-year period. Examinations revealed 2 additional calcified
      masses at the esophageal hiatus and retroperitoneum. The cut-surface of the
      operative specimens showed fibrous and mucinous appearance with many calcified
      islands. Microscopically, the lesion showed a gradual transform from the central
      immature area with fibroblasts and mucinous matrix, to the peripheral mature area
      with woven bone and osteoclasts (zoning phenomenon), which was compatible with
      the features of mature myositis ossificans. Myositis ossificans is an isolated,
      benign, nonneoplastic disease typically found in adolescence, after traumatic
      episode. Similar lesions have been found in the major musculature of patients
      with increased bleeding tendency. In the present case, idiopathic
      thrombocytopenic purpura was found to be associated and was suggested to be
      involved in initiating myositis ossificans. Still, it is extremely rare to
      observe lesions in these sites synchronously.

PMID- 18611938
TI  - Tuberous sclerosis complex with polycystic kidney disease of the adult type: the
      TSC2/ADPKD1 contiguous gene syndrome.
AB  - Although different diseases, tuberous sclerosis complex and autosomal dominant
      polycystic kidney disease have been seen in association, the molecular basis of
      this being the proximity of tuberous sclerosis complex 2 and polycystic kidney
      disease 1 genes on the same chromosome (16p13.3). Therefore, the classic
      autosomal dominant polycystic kidney disease renal phenotype may occur in the
      context of tuberous sclerosis complex disease as a result of large deletions
      involving both the polycystic kidney disease 1 and tuberous sclerosis complex 2
      genes. This is known as the tuberous sclerosis complex 2/autosomal dominant
      polycystic kidney disease 1 contiguous gene syndrome. The criteria for this
      condition are fulfilled when renal lesions typical for classic autosomal dominant
      polycystic kidney disease phenotype are associated with tuberous sclerosis
      complex phenotype. We present a new case of the sporadic form of this genetic
      disorder. The diagnosis of tuberous sclerosis complex in this patient was
      established on the presence of major and minor features, and the diagnosis of
      ADPKD was based on the presence of numerous large roundish renal cysts lined by a
      nondescript tubular epithelium. Sporadic cases of autosomal dominant polycystic
      kidney disease and tuberous sclerosis complex do occur. Molecular analysis was
      not performed because the patient's parents refused permission.

PMID- 18611939
TI  - Papillary adenocarcinoma of the thymus: case report and review of the literature.
AB  - A 44-year-old male with a mediastinal mass measuring 3.5 * 3.5 * 3 cm was
      diagnosed with papillary adenocarcinoma of the thymus. Other origins of papillary
      adenocarcinoma were excluded by clinical, imaging, and immunocytochemical methods
      before assuming this diagnosis. Residual thymus was seen under the microscope.
      Focal CD5 immunoreactivity was present. There was no associated thymoma. The
      patient underwent surgery, radiotherapy, and chemotherapy. He disclosed systemic
      recurrence at 18 months (subcutaneous nodule). He is alive after 24 months of
      follow-up with active disease. There had been only 7 cases of this rare entity
      published before.

PMID- 18611940
TI  - Clear cell change in colonic polyps.
AB  - In this study, the pathogenesis of clear cell change in colorectal epithelial
      lesions was studied. A total of 4 cases of clear cell change (1 hyperplasic polyp
      and 3 adenomas) were characterized using histochemistry, immunohistochemistry,
      and electron microscopy. All lesions developed in the left colon. In all, 1
      adenoma with clear cell dysplastic glands progressed to adenocarcinoma without
      clear cell change. Clear cell cytoplasmatic vacuoles were negative for glycogen
      and mucins (MUC 2, MUC 5AC). Ki-67 LI in clear cell adenoma components was lower
      than in common adenoma components of the same dysplasia grades (while p53 and
      beta-catenin were similarly expressed). Ultrastructural features of clear cell
      change showed features of lipid-like material. Clear cell change is found in
      hyperplastic and neoplastic lesions of the colon and is not due to the
      accumulation of glycogen or mucins. A degenerative nature of clear cell change is
      suggested by the demonstration of lipid-like material in the vacuoles of clear
      cells.

PMID- 18611941
TI  - Biotin-rich intranuclear inclusions: have you checked your immunohistochemical
      controls?
AB  - Intranuclear biotin interacts with avidin-biotin-complex used for viral
      immunoperoxidase detection giving false-positive results.

PMID- 18611942
TI  - Adenocarcinoma arising in an elderly patient's large ileal duplication.
AB  - Bowel duplications are rare congenital anomalies commonly found in pediatric
      patients; few cases may remain undetected until adulthood. Malignant
      carcinomatous changes are rare complications in intestinal duplications. An 88
      year-old female patient was referred to our surgical unit with the diagnosis of a
      large abdominal mass. An explorative laparotomy was performed, revealing a large
      (22 * 11 cm) neoplasm strictly connected to the lowest ileal segment and
      completely filling the pelvis. Definitive histology revealed a moderately
      differentiated adenocarcinoma developing in a duplication of the terminal ileum.
      The hypothesis of a gastrointestinal duplication should be evaluated in the
      differential diagnosis of large, complex, indeterminate masses located in or near
      the bowel; the possibility of neoplasm within the duplication should be
      considered.

PMID- 18611943
TI  - Incidence of melanocytic lesions of the conjunctiva in a review of 10 675
      ophthalmic specimens.
AB  - During the study period, 10,675 human ophthalmic specimens were received at The
      Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill
      University, Montreal, Canada. Of those, 271 were conjunctival lesions (2.5%),
      with 101 being classified as melanocytic: 50 (49.5%) nevi, 36 (35.6%) primary
      acquired melanoses, and 15 (14.9%) melanomas. After exclusion of referred cases,
      85 lesions were included in the study: 44 (51.7%) nevi, 33 (38.8%) primary
      acquired melanoses, and 8 (9.4%) melanomas. The most prevalent location was the
      bulbar conjunctiva. Conjunctival melanomas were most commonly found in an older
      age group than primary acquired melanosis or nevi. Conjunctival nevi were
      subdivided into compound (32.9%), subepithelial (16.4%), and junctional (2.3%).
      Primary acquired melanosis were further classified into primary acquired
      melanosis with atypia (8.2%) and primary acquired melanosis without atypia
      (30.5%). Primary acquired melanoses was the predisposing lesion in 75% of the
      cases of melanoma. In our sample, referral bias could alter the distribution of
      conjunctival pigmented lesions, with a shift toward the malignant end.

PMID- 18611944
TI  - Contribution to the definition of diagnostic criteria for Balkan endemic
      nephropathy.
AB  - BACKGROUND: Diagnostic criteria for Balkan endemic nephropathy (BEN) have not
      been precisely established. In the present study the predictive value of
      variables previously proposed as diagnostic criteria for BEN was examined.
      METHODS: The study involved 182 patients: 98 patients with BEN, 57 patients with
      other kidney diseases (20 with glomerulonephritis, 17 with tubulointerstitial
      diseases and 20 with hypertensive nephrosclerosis) and 27 healthy subjects. The
      BEN group comprised patients who fulfilled criteria for BEN and suspected BEN,
      together with patients with proteinuria and at least two tubular abnormalities or
      one tubular abnormality and a history of urothelial tumour. Demographic,
      clinical, laboratory and ultrasound variables of examined groups were combined in
      univariate/multivariate logistic regression analysis. RESULTS: Out of 28 analysed
      variables only urine alpha1-microglobulin (MG) and kidney length were selected as
      significant predictors in differentiating BEN from other kidney diseases and
      healthy controls. Using ROC curves the cutoff values of these variables and
      proteinuria and kidney volume, variables collinear with them, were found.
      Moderate sensitivity and specificity characterized all these cutoff values except
      for proteinuria, which provided high sensitivity and specificity in combination
      of BEN and healthy persons. The predictive value of different combinations of
      selected variables was not significantly different from the predictive value of
      each variable individually. CONCLUSIONS: Proteinuria, urine alpha1-MG, kidney
      length and volume were selected as significant predictors of BEN. Variables
      related to kidney failure as well as several tubular disorders (urine specific
      gravity, FENa and TRP) had an insignificant predictive value and could not be
      used for differential diagnosis of BEN.

PMID- 18611945
TI  - Soluble G protein of respiratory syncytial virus inhibits Toll-like receptor 3/4
      mediated IFN-beta induction.
AB  - Monocyte-derived dendritic cells (mDCs) recognize viral RNA extrinsically by Toll
      like receptor (TLR) 3 on the membrane and intrinsically retinoic acid-inducible
      gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) in the cytoplasm
      to induce type I IFNs and mDC maturation. When mDCs were treated with live or UV
      irradiated respiratory syncytial virus (RSV), early ( approximately 4 h)
      induction of IFN-beta usually occurs in other virus infections was barely
      observed. Live RSV subsequently replicated to activate the cytoplasmic IFN
      inducing pathway leading to robust type I IFN induction. We found that RSV
      initial attachment to cells blocked polyI:C-mediated IFN-beta induction, and this
      early IFN-beta-modulating event was abrogated by antibodies against envelope
      proteins of RSV, demonstrating the presence of a IFN-regulatory mode by early RSV
      attachment to host cells. By IFN-stimulated response element (ISRE) reporter
      analysis in HEK293 cells, polyI:C- or LPS-mediated ISRE activation was dose
      dependently inhibited by live and inactive RSV to a similar extent. Of the RSV
      envelope proteins, simultaneously expressed or exogenously added RSV G or soluble
      G (sG) proteins inhibited TLR3/4-mediated ISRE activation in HEK293 cells. sG
      proteins expressed in cells did not affect the RIG-I/MDA5 pathway but inhibited
      the TLR adaptor TRIF/TICAM-1 pathway for ISRE activation. Finally, extrinsically
      added sG protein suppressed the production of IFN-beta in mDCs. Although the
      molecular mechanism of this extrinsic functional mode of the RSV G glycoprotein
      (G protein) remains undetermined, G proteins may neutralize the fusion
      glycoprotein function that promotes IFN-mediated mDC modulation via TLR4 and may
      cause insufficient raising cell-mediated immunity against RSV.

PMID- 18611946
TI  - Novel DNA microarray system for analysis of nascent mRNAs.
AB  - Transcriptional activation and repression are a key step in the regulation of all
      cellular activities. The development of comprehensive analysis methods such as
      DNA microarray has advanced our understanding of the correlation between the
      regulation of transcription and that of cellular mechanisms. However, DNA
      microarray analysis based on steady-state mRNA (total mRNA) does not always
      correspond to transcriptional activation or repression. To comprehend these
      transcriptional regulations, the detection of nascent RNAs is more informative.
      Although the nuclear run-on assay can detect nascent RNAs, it has not been fully
      applied to DNA microarray analysis. In this study, we have developed a highly
      efficient method for isolating bromouridine-labeled nascent RNAs that can be
      successfully applied to DNA microarray analysis. This method can linearly amplify
      small amounts of mRNAs with little bias. Furthermore, we have applied this method
      to DNA microarray analysis from mouse G2-arrested cells and have identified
      several genes that exhibit novel expression profiles. This method will provide
      important information in the field of transcriptome analysis of various cellular
      processes.

PMID- 18611947
TI  - Discovering regulatory motifs in the Plasmodium genome using comparative
      genomics.
AB  - MOTIVATION: Understanding gene regulation in Plasmodium, the causative agent of
      malaria, is an important step in deciphering its complex life cycle as well as
      leading to possible new targets for therapeutic applications. Very little is
      known about gene regulation in Plasmodium, and in particular, few regulatory
      elements have been identified. Such discovery has been significantly hampered by
      the high A-T content of some of the genomes of Plasmodium species, as well as the
      challenge in associating discovered regulatory elements to gene regulatory
      cascades due to Plasmodium's complex life cycle. RESULTS: We report a new method
      of using comparative genomics to systematically discover motifs in Plasmodium
      without requiring any functional data. Different from previous methods, our
      method does not depend on sequence alignments, and thus is particularly suitable
      for highly divergent genomes. We applied our method to discovering regulatory
      motifs between the human parasite, P.falciparum, and its rodent-infectious
      relative, P.yoelii. We also tested our procedure against comparisons between
      P.falciparum and the primate-infectious, P.knowlesi. Our computational effort
      leads to an initial catalog of 38 distinct motifs, corresponding to over 16 200
      sites in the Plasmodium genome. The functionality of these motifs was further
      supported by their defined distribution within the genome as well as a
      correlation with gene expression patterns. This initial map provides a systematic
      view of gene regulation in Plasmodium, which can be refined as additional genomes
      become available. AVAILABILITY: The new algorithm, named motif discovery using
      orthologous sequences (MDOS), is available at http://www.ics.uci.edu/
      approximately xhx/project/mdos/.

PMID- 18611948
TI  - An intrastrand three-DNA-base interaction is a key specificity determinant of F
      transfer initiation and of F TraI relaxase DNA recognition and cleavage.
AB  - Bacterial conjugation, transfer of a single conjugative plasmid strand between
      bacteria, diversifies prokaryotic genomes and disseminates antibiotic resistance
      genes. As a prerequisite for transfer, plasmid-encoded relaxases bind to and
      cleave the transferred plasmid strand with sequence specificity. The crystal
      structure of the F TraI relaxase domain with bound single-stranded DNA suggests
      binding specificity is partly determined by an intrastrand three-way base-pairing
      interaction. We showed previously that single substitutions for the three
      interacting bases could significantly reduce binding. Here we examine the effect
      of single and double base substitutions at these positions on plasmid
      mobilization. Many substitutions reduce transfer, although the detrimental
      effects of some substitutions can be partially overcome by substitutions at a
      second site. We measured the affinity of the F TraI relaxase domain for several
      DNA sequence variants. While reduced transfer generally correlates with reduced
      binding affinity, some oriT variants transfer with an efficiency different than
      expected from their binding affinities, indicating ssDNA binding and cleavage do
      not correlate absolutely. Oligonucleotide cleavage assay results suggest the
      essential function of the three-base interaction may be to position the scissile
      phosphate for cleavage, rather than to directly contribute to binding affinity.

PMID- 18611949
TI  - Requirement of histone deacetylase1 (HDAC1) in signal transducer and activator of
      transcription 3 (STAT3) nucleocytoplasmic distribution.
AB  - Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription
      factor that plays a crucial role in interleukin-6 (IL-6) signaling, mediating the
      acute-phase induction of the human Angiotensinogen (hAGT) gene in hepatocytes. We
      showed earlier that IL-6 induces acetylation of the STAT3 NH(2)-terminus by the
      recruitment of the p300 coactivator. We had also observed a physical interaction
      of STAT3 and Histone Deacetylase1 (HDAC1) in an IL-6-dependent manner that leads
      to transcriptional repression. In this study, we sought to elucidate the
      mechanism by which HDAC1 controls STAT3 transcriptional activity. Here, we mapped
      the interacting domains of both STAT3 and HDAC1 and found that the COOH-terminal
      domain of HDAC1 is necessary for IL-6-induced STAT3 transcriptional repression,
      whereas the NH(2)-terminal acetylation domain of STAT3 is required for HDAC1
      binding. Interestingly, over expression of HDAC1 in HepG2 cells leads to
      significantly reduced amounts of nuclear STAT3 after IL-6 induction, whereas
      silencing of HDAC1 resulted in accumulation of total and acetylated STAT3 in the
      nucleus. We have found that HDAC1 knockdown also interferes with the
      responsiveness of the STAT3-dependent MCP1 target gene expression to IL-6, as
      confirmed by real-time RT-PCR analysis. Together, our study reveals the novel
      functional consequences of IL-6-induced STAT3-HDAC1 interaction on
      nucleocytoplasmic distribution of STAT3.

PMID- 18611950
TI  - TAp73beta and DNp73beta activate the expression of the pro-survival caspase-2S.
AB  - p73, the p53 homologue, exists as a transactivation-domain-proficient TAp73 or
      deficient deltaN(DN)p73 form. Expectedly, the oncogenic DNp73 that is capable of
      inactivating both TAp73 and p53 function, is over-expressed in cancers. However,
      the role of TAp73, which exhibits tumour-suppressive properties in gain or loss
      of function models, in human cancers where it is hyper-expressed is unclear. We
      demonstrate here that both TAp73 and DNp73 are able to specifically transactivate
      the expression of the anti-apoptotic member of the caspase family, caspase-2(S).
      Neither p53 nor TAp63 has this property, and only the p73beta form, but not the
      p73alpha form, has this competency. Caspase-2 promoter analysis revealed that a
      non-canonical, 18 bp GC-rich Sp-1-binding site-containing region is essential for
      p73beta-mediated activation. However, mutating the Sp-1-binding site or silencing
      Sp-1 expression did not affect p73beta's transactivation ability. In vitro DNA
      binding and in vivo chromatin immunoprecipitation assays indicated that p73beta
      is capable of directly binding to this region, and consistently, DNA binding p73
      mutant was unable to transactivate caspase-2(S). Finally, DNp73beta over
      expression in neuroblastoma cells led to resistance to cell death, and
      concomitantly to elevated levels of caspase-2(S.) Silencing p73 expression in
      these cells led to reduction of caspase-2(S) expression and increased cell death.
      Together, the data identifies caspase-2(S) as a novel transcriptional target
      common to both TAp73 and DNp73, and raises the possibility that TAp73 may be over
      expressed in cancers to promote survival.

PMID- 18611951
TI  - The RNA-binding protein TbDRBD3 regulates the stability of a specific subset of
      mRNAs in trypanosomes.
AB  - In trypanosomes, the apparent lack of regulation of RNA polymerase II-dependent
      transcription initiation poses a challenge to understand how these eukaryotes
      adjust gene expression to adapt to the contrasting environments they find during
      their life cycles. Evidence so far indicates that mRNA turnover and translation
      are the major control points in which regulation is exerted in trypanosomes.
      However, very little is known about which proteins are involved, and how do they
      regulate the abundance and translation of different mRNAs in different life
      stages. In this work, an RNA-binding protein, TbDRBD3, has been identified by
      affinity chromatography, and its function addressed using RNA interference,
      microarray analysis and immunoprecipitation of mRNA-protein complexes. The
      results obtained indicate that TbDRBD3 binds to a subset of developmentally
      regulated mRNAs encoding membrane proteins, and that this association promotes
      the stabilization of the target transcripts. These observations raise the
      possibility that TbDRBD3-mRNA complexes act as a post-transcriptional operon, and
      provide a framework to interpret how trypanosomes regulate gene expression in the
      absence of transcriptional control.

PMID- 18611952
TI  - Global analysis of in vivo Foxa2-binding sites in mouse adult liver using
      massively parallel sequencing.
AB  - Foxa2 (HNF3 beta) is a one of three, closely related transcription factors that
      are critical to the development and function of the mouse liver. We have used
      chromatin immunoprecipitation and massively parallel Illumina 1G sequencing (ChIP
      Seq) to create a genome-wide profile of in vivo Foxa2-binding sites in the adult
      liver. More than 65% of the approximately 11.5 k genomic sites associated with
      Foxa2 binding, mapped to extended gene regions of annotated genes, while more
      than 30% of intragenic sites were located within first introns. 20.5% of all
      sites were further than 50 kb from any annotated gene, suggesting an association
      with novel gene regions. QPCR analysis demonstrated a strong positive correlation
      between peak height and fold enrichment for Foxa2-binding sites. We measured the
      relationship between Foxa2 and liver gene expression by overlapping Foxa2-binding
      sites with a SAGE transcriptome profile, and found that 43.5% of genes expressed
      in the liver were also associated with Foxa2 binding. We also identified
      potential Foxa2-interacting transcription factors whose motifs were enriched near
      Foxa2-binding sites. Our comprehensive results for in vivo Foxa2-binding sites in
      the mouse liver will contribute to resolving transcriptional regulatory networks
      that are important for adult liver function.

PMID- 18611953
TI  - SNP-specific extraction of haplotype-resolved targeted genomic regions.
AB  - The availability of genotyping platforms for comprehensive genetic analysis of
      complex traits has resulted in a plethora of studies reporting the association of
      specific single-nucleotide polymorphisms (SNPs) with common diseases or drug
      responses. However, detailed genetic analysis of these associated regions that
      would correlate particular polymorphisms to phenotypes has lagged. This is
      primarily due to the lack of technologies that provide additional sequence
      information about genomic regions surrounding specific SNPs, preferably in
      haploid form. Enrichment methods for resequencing should have the specificity to
      provide DNA linked to SNPs of interest with sufficient quality to be used in a
      cost-effective and high-throughput manner. We describe a simple, automated method
      of targeting specific sequences of genomic DNA that can directly be used in
      downstream applications. The method isolates haploid chromosomal regions flanking
      targeted SNPs by hybridizing and enzymatically elongating oligonucleotides with
      biotinylated nucleotides based on their selective binding to unique sequence
      elements that differentiate one allele from any other differing sequence. The
      targeted genomic region is captured by streptavidin-coated magnetic particles and
      analyzed by standard genotyping, sequencing or microarray analysis. We applied
      this technology to determine contiguous molecular haplotypes across a
      approximately 150 kb genomic region of the major histocompatibility complex.

PMID- 18611954
TI  - Type 2 diabetes mellitus and risk of non-Hodgkin lymphoma: a systematic review
      and meta-analysis.
AB  - Type 2 diabetes mellitus is associated with altered immune function and chronic
      inflammation. Both of these immune conditions are implicated in the pathogenesis
      of non-Hodgkin lymphoma. The authors performed a systematic review to summarize
      findings from the current literature on the association between history of type 2
      diabetes mellitus and risk of non-Hodgkin lymphoma. Ten case-control studies and
      three prospective cohort studies were included in this review. Meta-analysis
      found that a history of type 2 diabetes mellitus was positively associated with
      overall non-Hodgkin lymphoma risk. However, there was significant heterogeneity
      between studies. Study design was an important source of heterogeneity. The rate
      ratio between type 2 diabetes mellitus and non-Hodgkin lymphoma was found to be
      1.18 (95% confidence interval: 0.99, 1.42) among case-control studies and 1.79
      (95% confidence interval: 1.30, 2.47) among the prospective cohort studies.
      Weaknesses were identified in some of the included studies in the areas of case
      and control selection, measurement of covariates and non-Hodgkin lymphoma, and
      confounding control. Although a positive association between type 2 diabetes
      mellitus and risk of non-Hodgkin lymphoma was suggested, the evidence is
      inconclusive because of methodological limitations of the included case-control
      studies. More prospective studies with improved control of confounding are needed
      to confirm these findings.

PMID- 18611955
TI  - Perceived stress and cause-specific mortality among men and women: results from a
      prospective cohort study.
AB  - The authors assessed the effect of psychological stress on total and cause
      specific mortality among men and women. In 1981-1983, the 12,128 Danish
      participants in the Copenhagen City Heart Study were asked two questions on
      stress intensity and frequency and were followed in a nationwide registry until
      2004, with <0.1% loss to follow-up. Sex differences were found in the relations
      between stress and mortality (p = 0.02). After adjustments, men with high stress
      versus low stress had higher all-cause mortality (hazard ratio (HR) = 1.32, 95%
      confidence interval (CI): 1.15, 1.52). This finding was most pronounced for
      deaths due to respiratory diseases (high vs. low stress: HR = 1.79, 95% CI: 1.10,
      2.91), external causes (HR = 3.07, 95% CI: 1.65, 5.71), and suicide (HR = 5.91,
      95% CI: 2.47, 14.16). High stress was related to a 2.59 (95% CI: 1.20, 5.61)
      higher risk of ischemic heart disease mortality for younger, but not older, men.
      In general, the effects of stress were most pronounced among younger and
      healthier men. No associations were found between stress and mortality among
      women, except among younger women with high stress, who experienced lower cancer
      mortality (HR = 0.51, 95% CI: 0.28, 0.92). Future preventive strategies may be
      targeted toward stress as a risk factor for premature death among middle-aged,
      presumably healthy men.

PMID- 18611956
TI  - Effect of formal statistical significance on the credibility of observational
      associations.
AB  - The author evaluated the implications of nominal statistical significance for
      changing the credibility of null versus alternative hypotheses across a large
      number of observational associations for which formal statistical significance (p
      < 0.05) was claimed. Calculation of the Bayes factor (B) under different
      assumptions was performed on 272 observational associations published in 2004
      2005 and a data set of 50 meta-analyses on gene-disease associations (752
      studies) for which statistically significant associations had been claimed (p <
      0.05). Depending on the formulation of the prior, statistically significant
      results offered less than strong support to the credibility (B > 0.10) for 54-77%
      of the 272 epidemiologic associations for diverse risk factors and 44-70% of the
      50 associations from genetic meta-analyses. Sometimes nominally statistically
      significant results even decreased the credibility of the probed association in
      comparison with what was thought before the study was conducted. Five of six meta
      analyses with less than substantial support (B > 0.032) lost their nominal
      statistical significance in a subsequent (more recent) meta-analysis, while this
      did not occur in any of seven meta-analyses with decisive support (B < 0.01). In
      these large data sets of observational associations, formal statistical
      significance alone failed to increase much the credibility of many postulated
      associations. Bayes factors may be used routinely to interpret "significant"
      associations.

PMID- 18611957
TI  - The role of flexible bronchoscopy in pediatric pulmonary tuberculosis.

PMID- 18611958
TI  - Severe mitral regurgitation and hepatopulmonary hydatid cysts: what should be
      treated first?
AB  - Hydatid cyst can simultaneously affect the liver and lung. Some patients might
      have additional comorbidities that can make management more challenging. Here, we
      present a 10-year-old boy with hepatopulmonary hydatid cysts and severe mitral
      regurgitation, who was successfully managed with a staged surgical approach
      treating the lung first, followed by the liver and finally, the heart.

PMID- 18611960
TI  - Progression of meiotic recombination requires structural maturation of the
      central element of the synaptonemal complex.
AB  - The synaptonemal complex is an elaborate meiosis-specific supramolecular protein
      assembly that promotes chromosome synapsis and meiotic recombination. We
      inactivated the meiosis-specific gene Tex12 and found that TEX12 is essential for
      progression of meiosis in both male and female germ cells. Structural analysis of
      the synaptonemal complex in Tex12-/- meiocytes revealed a disrupted central
      element structure, a dense structure residing between the synapsed homologous
      chromosomes. Chromosome synapsis is initiated at multiple positions along the
      paired homologous chromosomes in Tex12-/- meiotic cells, but fails to propagate
      along the chromosomes. Furthermore, although meiotic recombination is initiated
      in Tex12-/- meiotic cells, these early recombination events do not develop into
      meiotic crossovers. Hence, the mere initiation of synapsis is not sufficient to
      support meiotic crossing-over. Our results show that TEX12 is a component of the
      central element structure of the synaptonemal complex required for propagation of
      synapsis along the paired homologous chromosomes and maturation of early
      recombination events into crossovers.

PMID- 18611959
TI  - Effectiveness of 3-day amoxycillin vs. 5-day co-trimoxazole in the treatment of
      non-severe pneumonia in children aged 2-59 months of age: a multi-centric open
      labeled trial.
AB  - This cluster randomized, open labeled trial was conducted to compare the
      effectiveness of 3 days of oral amoxycillin and 5 days of co-trimoxazole
      treatment in terms of clinical failure in children with World Health Organization
      (WHO) defined non-severe pneumonia in primary health centers in rural India.
      Participants were children aged 2-59 months with WHO defined non-severe
      pneumonia, with or without wheeze, who were accessible to follow up. From seven
      primary health centers in each arm, 2009 cases were randomized, 993 and 1016 in
      treatment with amoxycillin and co-trimoxazole, respectively. Fever was present in
      1247 (62.1%) and wheeze in 443 (22.1%). There was good adherence and low loss to
      follow-up. Clinical failure on amoxycillin and co-trimoxazole on intention to
      treat analysis was 137 and 97, respectively (absolute difference = 0.04, 95%
      confidence interval: - 0.035-0.12). We conclude that there was no difference in
      effectiveness of oral co-trimoxazole or amoxycillin in treating non-severe
      pneumonia.

PMID- 18611961
TI  - Binding of soluble fibronectin to integrin alpha5 beta1 - link to focal adhesion
      redistribution and contractile shape.
AB  - Focal adhesions are randomly distributed across the ventral surface or along the
      edge of epithelial cells. In fibroblasts they orient centripetally and
      concentrate at a few peripheral sites connecting long F-actin stress fibers,
      causing a typical elongated, contractile morphology. Extensive remodeling of
      adhesions in fibroblasts also takes part in fibronectin fibrillogenesis, a
      process that depends on Rho-mediated contractility and results in the formation
      of a fibronectin matrix. Our current study shows that all these fibroblast
      characteristics are controlled by the ability of integrin alpha5 beta1 to bind
      soluble fibronectin molecules in their compact inactive conformation. The
      hypervariable region of the ligand-binding I-like domain of integrin alpha5 beta1
      supports binding of soluble fibronectin. This supports the distribution of
      centripetally orientated focal adhesions in distinct peripheral sites, Rho
      activation and fibronectin fibrillogenesis through a mechanism that does not
      depend on Syndecan-4. Integrin alpha v beta3, even when locked in high affinity
      conformations for the RGD recognition motif shows no appreciable binding of
      soluble fibronectin and, consequently, fails to support the typical fibroblast
      focal adhesion distribution, Rho activity and fibronectin fibrillogenesis in the
      absence of integrin alpha5 beta1. The ability of alpha5 beta1 integrin to
      interact with soluble fibronectin may thus drive the cell-matrix adhesion and
      cytoskeletal organization required for a contractile, fibroblast-like morphology,
      perhaps explaining why alpha5 beta1 integrin, similarly to fibronectin, is
      essential for development.

PMID- 18611962
TI  - The secreted Dictyostelium protein CfaD is a chalone.
AB  - Dictyostelium discoideum cells secrete CfaD, a protein that is similar to
      cathepsin proteases. Cells that lack cfaD proliferate faster and reach a higher
      stationary-phase density than wild-type cells, whereas cells that overexpress
      CfaD proliferate slowly and reach the stationary phase when at a low density. On
      a per-nucleus basis, CfaD affects proliferation but not growth. The drawback of
      not having CfaD is a reduced spore viability. Recombinant CfaD has no detectable
      protease activity but, when added to cells, inhibits the proliferation of wild
      type and cfaD(-) cells. The secreted protein AprA also inhibits proliferation.
      AprA is necessary for the effect of CfaD on proliferation. Molecular-sieve
      chromatography indicates that in conditioned growth medium, the 60 kDa CfaD is
      part of a approximately 150 kDa complex, and both chromatography and pull-down
      assays suggest that CfaD interacts with AprA. These results suggest that two
      interacting proteins may function together as a chalone signal in a negative
      feedback loop that slows Dictyostelium cell proliferation.

PMID- 18611963
TI  - A role for Q/N-rich aggregation-prone regions in P-body localization.
AB  - P-bodies are cytoplasmic foci that are sites of mRNA degradation and
      translational repression. It is not known what causes the accumulation of RNA
      degradation factors in P-bodies, although RNA is required. The yeast Lsm1-7p
      complex (comprising Lsm1p to Lsm7p) is recruited to P-bodies under certain stress
      conditions. It is required for efficient decapping and degradation of mRNAs, but
      not for the assembly of P-bodies. Here we show that the Lsm4p subunit and its
      asparagine-rich C-terminus are prone to aggregation, and that this tendency to
      aggregate promotes efficient accumulation of Lsm1-7p in P-bodies. The presence of
      glutamine- and/or asparagine-rich (Q/N-rich) regions in other P-body components
      suggests a more general role for aggregation-prone residues in P-body
      localization and assembly. This is supported by reduced P-body accumulation of
      Ccr4p, Pop2p and Dhh1p after deletion of these domains, and by the observed
      aggregation of the Q/N-rich region from Ccr4p.

PMID- 18611964
TI  - Obesity as a risk factor for the progression of paroxysmal to permanent atrial
      fibrillation: a longitudinal cohort study of 21 years.
AB  - AIMS: Obesity has been shown to be a risk factor for first atrial fibrillation
      (AF), but whether it is associated with progression from paroxysmal to permanent
      AF is unknown. METHODS AND RESULTS: In this longitudinal cohort study, Olmsted
      County, MN residents confirmed to have developed paroxysmal AF during 1980-2000
      were identified and followed passively to 2006. The interrelationships of body
      mass index (BMI), left atrial (LA) size, and progression to permanent AF were
      analysed. Of a total of 3248 patients (mean age 71 +/- 15 years; 54% men)
      diagnosed with paroxysmal AF, 557 (17%) progressed to permanent AF (unadjusted
      incidence, 36/1000 person-years) over a median follow-up period of 5.1 years
      (interquartile range 1.2-9.4). Adjusting for age and sex, BMI independently
      predicted the progression to permanent AF (hazard ratio, HR 1.04, CI 1.03-1.06; P
      < 0.0001). Compared with normal BMI (18.5-24.9 kg/m(2)), obesity (30-34.9
      kg/m(2)) and severe obesity (>or=35 kg/m(2)) were associated with increased risk
      for progression [HR 1.54 (CI 1.2-2.0; P = 0.0004) and 1.87 (CI 1.4-2.5; P <
      0.0001, respectively)]. BMI remained highly significant even after multiple
      adjustments. In the subgroup with echocardiographic assessment (n = 744), LA
      volume was incremental to BMI for independent prediction of progression after
      multiple adjustments, and did not weaken the association between BMI and
      progression to permanent AF (HR 1.04; CI 1.02-1.05; P < 0.0001). CONCLUSION:
      There was a graded risk relationship between BMI and progression from paroxysmal
      to permanent AF. This relationship was not weakened by LA volume, which was
      independent of and incremental to BMI for the prediction of progression to
      permanent AF.

PMID- 18611965
TI  - Hypertrophic cardiomyopathy misinterpreted.

PMID- 18611966
TI  - Echocardiographic evaluation of patients with undocumented arrhythmias occurring
      in adults late after repair of tetralogy of Fallot.
AB  - AIMS: Arrhythmias occurring late after repair of tetralogy of Fallot (ToF) are
      common. Due to the risk of sudden cardiac death, attention is focused towards
      ventricular tachycardias (VT). The aims of this study were to determine the
      clinical profile of patients with known benign and malignant arrhythmias and to
      assess patients with palpitations without documented arrhythmias. METHODS AND
      RESULTS: Fifty-two patients with prior ToF repair were included in this study
      (mean follow-up: 18+/-7.3 years). Echocardiographic measurements such as left
      ventricular ejection fraction, left and right atrial (LA and RA) diameters, left
      and right ventricular diameters (LVEDD and RVEDD), pulmonary and tricuspid
      regurgitation (TI and PI) and electrocardiographic parameters such as QRS
      duration, P-wave duration, P-wave dispersion were obtained and compared in
      patients with and without a history of palpitations. The same comparisons were
      performed between patients with documented supraventricular tachycardias (SVT)
      and VT. Twenty-seven of 52 patients had a clinical history of palpitations. The
      remaining 25 patients served as controls. Eleven patients had documented SVT and
      6 patients had documented VT. In patients with documented SVT, the RA size and
      the QRS durations were significantly higher than in the controls (RA: 55.3+/-5.6
      vs. 47.4+/-4.8 mm, P=0.03, QRS: 160.0+/-25.9 vs. 131.8+/-26.1 ms, P=0.01). In
      patients with VT, the LVEDD, LA, and QRS durations showed significantly higher
      values compared with the control patients (LVEDD: 53.5+/-4.7 vs. 45.6+/-6.8 mm;
      LA: 56.0+/-3.4 vs. 48.5+/-4.8 mm, P=0.01; QRS: 169.5+/-29.7 ms vs. 131.8+/-26.1
      ms; P=0.001). The only significant differences between patients with and without
      palpitations were the RA size (58.2+/-3.9 vs. 50.5+/-5.2 mm, P=0.02) and the P
      wave dispersion (26.8+/-15.2 vs. 16.6+/-4.3 ms, P=0.04). CONCLUSION: Our present
      data suggest that undocumented arrhythmias are most likely SVTs and are
      associated with increased RA size.

PMID- 18611967
TI  - Ventricular optimization of biventricular pacing: a systematic review.
AB  - Biventricular pacing has been shown to improve the overall clinical outcomes in
      patients with systolic heart failure and ventricular conduction delay on
      electrocardiogram. As correction of ventricular dyssynchrony is the putative
      mechanism of benefit, biventricular pacing is also termed as cardiac
      resynchronization therapy. The development of separate programmability of right
      and left ventricular output has led to a growing number of reports on the
      potential benefit of optimization of cardiac resynchronization by sequential
      biventricular pacing with different techniques and endpoints. This systematic
      review summarizes the current data for the optimization of sequential (V-V delay)
      compared with (default) simultaneous biventricular pacing in heart failure.

PMID- 18611968
TI  - Incident and recurrent back injuries among union carpenters.
AB  - AIMS: To describe incident and recurrent work-related back injuries among union
      carpenters, describe the hazard function for each and associated risk factors,
      and explore predictors of subsequent musculoskeletal back injury based on
      different definitions of the initial injury. METHODS: This study identified a
      dynamic cohort of 18 768 carpenters who worked in the State of Washington 1989
      2003, their hours worked each month, and their work-related back injuries and
      medical claims for treatment including ICD-9 codes. Using Poisson regression we
      calculated rates and rate ratios (RRs) of incident and recurrent injury adjusting
      for age, gender, union tenure and type of carpentry work. Predictors of
      subsequent musculoskeletal back injury were explored based on different
      definitions of the incident injury, as were time periods of greatest risk
      following return to work. RESULTS: Recurrent back injuries occurred at a rate 80%
      higher than initial injuries. Survival curves were significantly different for
      incident and recurrent injuries, but patterns of relative risk were similar.
      Individuals with greatest union tenure were at lowest risk, likely reflecting a
      healthy worker effect or lower physical exposures with seniority. Individuals
      with long periods of work disability with their first injury were at particularly
      high risk of subsequent musculoskeletal injury compared with those with no prior
      history (RR 2.3; 95% CI 2.0 to 2.7), as were individuals with degenerative
      diagnoses (RR 2.0; 95% CI 1.5 to 2.6). Risk for second injury peaked between 1000
      and 1500 h after return to work and then gradually declined. CONCLUSIONS:
      Carpenters with long periods of work disability following back injury warrant
      accommodation and perhaps better rehabilitation efforts to avoid re-injury.
      Challenges to workplace accommodation and limited ability to clearly define
      readiness to return to work following injury demonstrate the need for primary
      prevention of back injuries through attention to engineering solutions among
      carpenters involved in strenuous work.

PMID- 18611969
TI  - Sickness absence as a prognostic marker for common chronic conditions: analysis
      of mortality in the GAZEL study.
AB  - OBJECTIVES: To determine whether sickness absence is a prognostic marker in terms
      of mortality among people with common chronic conditions. METHODS: Prospective
      occupational cohort study of 13,077 men and 4871 women aged 37-51 from the
      National Gas and Electricity Company, France. Records of physician-certified
      sickness absences over a 3-year period were obtained from employers' registers.
      Chronic conditions were assessed in annual surveys over the same period. The main
      outcome measure was all-cause mortality (803 deaths, mean follow-up after
      assessment of sickness absence: 13.9 years). RESULTS: In Cox proportional hazard
      models adjusted for age, sex, socioeconomic position and co-morbidity, >28 annual
      sickness-absence days versus no absence days was associated with an excess
      mortality risk among those with cancer (hazard ratio 5.4, 95% CI 2.2 to 13.1),
      depression (1.7, 1.1 to 2.8), chronic bronchitis or asthma (2.7, 1.6 to 4.6) and
      hypertension (1.6, 1.0 to 2.6). The corresponding hazard ratios for more than
      five long (>14 days) sickness-absence episodes per 10 person-years versus no such
      episodes were 5.4 (2.2 to 13.1), 1.8 (1.3 to 2.7), 2.0 (1.3 to 3.2) and 1.8 (1.2
      to 2.7), respectively. Areas under receiver operating characteristics curves for
      these absence measures varied between 0.56 and 0.73, indicating the potential of
      these measures to distinguish groups at high risk of mortality. The findings were
      consistent across sex, age and socioeconomic groups and in those with and without
      co-morbid conditions. CONCLUSION: Data on sickness absence may provide useful
      prognostic information for common chronic conditions at the population level.

PMID- 18611970
TI  - Impact of TCF7L2 rs7903146 on insulin secretion and action in young and elderly
      Danish twins.
AB  - OBJECTIVE: We investigated the regulation and metabolic effects of TCF7L2 gene
      expression in human sc fat and skeletal muscle and the impact of the TCF7L2,
      rs7903146, T-allele on gene expression and measures of glucose metabolism
      including insulin secretion and peripheral and hepatic insulin action. RESEARCH
      DESIGN AND METHODS: The rs7903146 was genotyped in 1) a population-based sample
      of 587 twins (55-64 yr) with glucose tolerance ranging from normal to type 2
      diabetes and 2) a population of 196 nondiabetic young (22-31 yr) and elderly (57
      66 yr) twins. All subjects underwent oral glucose tolerance tests, and population
      2 was additionally examined with iv glucose tolerance tests and hyperinsulinemic,
      euglycemic clamps. RESULTS: Elderly T-allele carriers had decreased plasma
      insulin responses and lower disposition index, whereas insulinogenic index was
      similar between genotype groups. Elderly nondiabetic T-allele carriers had
      increased peripheral insulin sensitivity (P = 0.03). Young T-allele carriers had
      impaired hepatic insulin sensitivity (P = 0.04) independent of plasma insulin
      levels. TCF7L2 gene expression in skeletal muscle and adipose tissue was not
      explained by genotype, sex, aerobic capacity, birth, or adult anthropometry and
      was not associated with in vivo glucose metabolism. CONCLUSIONS: The rs7903146 T
      allele associates with hepatic insulin resistance and diminished glucose
      stimulated plasma insulin secretion. Our study does not provide evidence of a
      role of TCF7L2 gene expression in sc fat tissue and muscle tissue in the
      regulation of glucose homeostasis. This suggests that the primary defect of
      rs7903146 T-allele carriers is impairment of insulin secretion rather than a
      defect in insulin action in peripheral tissues.

PMID- 18611971
TI  - Risk of thyroid disease in individuals with celiac disease.
AB  - BACKGROUND: It has been suggested that celiac disease is associated with thyroid
      disease. Earlier studies, however, have been predominately cross-sectional and
      have often lacked controls. There is hence a need for further research. In this
      study, we estimated the risk of thyroid disease in individuals with celiac
      disease from a general population cohort. METHODS: A total of 14,021 individuals
      with celiac disease (1964-2003) and a matched reference population of 68,068
      individuals were identified through the Swedish national registers. Cox
      regression estimated the risk of thyroid disease in subjects with celiac disease.
      Analyses were restricted to individuals with a follow-up of more than 1 yr and
      with no thyroid disease before study entry or within 1 yr after study entry.
      Conditional logistic regression estimated the odds ratio for subsequent celiac
      disease in individuals with thyroid disease. RESULTS: Celiac disease was
      positively associated with hypothyroidism [hazard ratio (HR) = 4.4; 95%
      confidence interval (CI) = 3.4-5.6; P < 0.001], thyroiditis (HR = 3.6; 95% CI
      =1.9-6.7; P < 0.001) and hyperthyroidism (HR = 2.9; 95% CI = 2.0-4.2; P < 0.001).
      The highest risk estimates were found in children (hypothyroidism, HR = 6.0 and
      95% CI = 3.4-10.6; thyroiditis, HR = 4.7 and 95% CI = 2.1-10.5; hyperthyroidism,
      HR = 4.8 and 95% CI = 2.5-9.4). In post hoc analyses, where the reference
      population was restricted to inpatients, the adjusted HR was 3.4 for
      hypothyroidism (95% CI = 2.7-4.4; P < 0.001), 3.3 for thyroiditis (95% CI = 1.5
      7.7; P < 0.001), and 3.1 for hyperthyroidism (95% CI = 2.0-4.8; P < 0.001).
      CONCLUSION: Celiac disease is associated with thyroid disease, and these
      associations were seen regardless of temporal sequence. This indicates shared
      etiology and that these individuals are more susceptible to autoimmune disease.

PMID- 18611972
TI  - Clinical and biochemical impact of the d3 growth hormone receptor genotype in
      acromegaly.
AB  - CONTEXT: Lack of exon 3 of the GH receptor (d3-GHR) has been associated with
      increased responsiveness to GH therapy. By analogy, we hypothesized that patients
      with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and
      biochemical picture. OBJECTIVE: Our objective was to determine whether the GHR
      genotype, by modifying tissue sensitivity to GH, influences the
      clinical/biochemical expression of acromegaly and its outcome after treatment.
      SETTING: The study was conducted at a specialized clinic at a tertiary care
      hospital. DESIGN, PATIENTS, AND METHODS: We conducted a prospective genotype
      investigation and retrospective analysis and correlation with clinical,
      biochemical, and outcome data from a group of 148 patients. Samples from 175
      healthy blood donors were used as controls. GHR genotyping was performed by real
      time PCR. MAIN OUTCOME MEASURES: We assessed prevalence of the three GHR
      genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and
      baseline as well as post-therapeutic characteristics. RESULTS: Prevalence of the
      fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to
      what was found in the controls. Baseline characteristics were similar in carriers
      of the three genotypes. A positive correlation between IGF-I and log GH
      concentrations was significant only in homo- or heterozygous d3 carriers. Among
      d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds
      ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had
      significantly higher IGF-I concentrations after treatment. Multiple regression
      analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest
      predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence
      interval = 0.65-2.58). CONCLUSIONS: The absence of exon 3 of the GHR may be
      associated with a more morbid acromegalic clinical and biochemical picture and a
      lower chance of achieving IGF-I normalization after therapy.

PMID- 18611973
TI  - Insulin-like factor 3 levels in second-trimester amniotic fluid.
AB  - BACKGROUND: According to animal studies, the testicular Leydig cell hormone
      insulin-like factor 3 (Insl3) exerts a fundamental role in abdominal testis
      translocation, which occurs in the beginning of the second trimester in humans.
      Despite this, human prenatal INSL3 production has been poorly investigated.
      METHODS: Amniotic fluid from 91 pregnant women undergoing amniocentesis was
      analyzed for INSL3 and testosterone (T) levels. Data were related to gestational
      age (15-25 wk) at amniocentesis and to sex (45 males and 48 females). RESULTS:
      INSL3 was present in amniotic fluid from all but one of the investigated male
      fetuses (range: <0.02-0.36 ng/ml; mean +/- sd: 0.12 +/- 0.07), whereas the
      hormone was undetectable in the female fetuses. T was significantly higher in
      male (range: 0.54-1.71 nmol/liter; mean +/- sd: 1.04 +/- 0.30) as compared with
      in female amniotic fluid (range: 0.19-0.50 nmol/liter; mean +/- sd: 0.34 +/-
      0.06) (P < 0.001). In males there was no correlation between INSL3 and T. A
      statistically borderline negative association was found between INSL3 and
      gestational age (P = 0.07), whereas the corresponding association was not
      significant for T (P = 0.12). In contrast, T in females correlated positively
      with gestational age (P = 0.02). CONCLUSIONS: INSL3 is clearly present in human
      male amniotic fluid in the second trimester, where abdominal testis translocation
      takes place. In contrast, the hormone is undetectable in female amniotic fluid.
      The prenatal presence of INSL3 supports the hypothesis that this hormone is
      essential for testicular descent in humans.

PMID- 18611974
TI  - Expression of insulin-like growth factor-II and its receptor in pediatric and
      adult adrenocortical tumors.
AB  - BACKGROUND: Adrenocortical tumors are heterogeneous neoplasms with incompletely
      understood pathogenesis. IGF-II overexpression has been consistently demonstrated
      in adult adrenocortical carcinomas. OBJECTIVES: The objective of the study was to
      analyze expression of IGF-II and its receptor (IGF-IR) in pediatric and adult
      adrenocortical tumors and the effects of a selective IGF-IR kinase inhibitor (NVP
      AEW541) on adrenocortical tumor cells. PATIENTS: Fifty-seven adrenocortical
      tumors (37 adenomas and 20 carcinomas) from 23 children and 34 adults were
      studied. METHODS: Gene expression was determined by quantitative real-time PCR.
      Cell proliferation and apoptosis were analyzed in NCI H295 cells and a new cell
      line established from a pediatric adrenocortical adenoma. RESULTS: IGF-II
      transcripts were overexpressed in both pediatric adrenocortical carcinomas and
      adenomas. Otherwise, IGF-II was mainly overexpressed in adult adrenocortical
      carcinomas (270.5 +/- 130.2 vs. 16.1 +/- 13.3; P = 0.0001). IGF-IR expression was
      significantly higher in pediatric adrenocortical carcinomas than adenomas (9.1 +/
      3.1 vs. 2.6 +/- 0.3; P = 0.0001), whereas its expression was similar in adult
      adrenocortical carcinomas and adenomas. IGF-IR expression was a predictor of
      metastases in pediatric adrenocortical tumors in univariate analysis (hazard
      ratio 1.84; 95% confidence interval 1.28-2.66; P = 0.01). Furthermore, NVP-AEW541
      blocked cell proliferation in a dose- and time-dependent manner in both cell
      lines through a significant increase of apoptosis. CONCLUSION: IGF-IR
      overexpression was a biomarker of pediatric adrenocortical carcinomas.
      Additionally, a selective IGF-IR kinase inhibitor had antitumor effects in adult
      and pediatric adrenocortical tumor cell lines, suggesting that IGF-IR inhibitors
      represent a promising therapy for human adrenocortical carcinoma.

PMID- 18611975
TI  - Nocturnal glucose metabolism after bedtime injection of insulin glargine or
      neutral protamine hagedorn insulin in patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Insulin glargine is a long-acting human insulin analog often
      administered at bedtime to patients with type 2 diabetes. It reduces fasting
      blood glucose levels more efficiently and with less nocturnal hypoglycemic events
      compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime
      injections of insulin glargine and NPH insulin were compared overnight and in the
      morning. METHODS: In 10 type 2 diabetic patients, euglycemic clamps were
      performed, including [6,6'](2)H(2) glucose, to study the rate of disappearance
      (Rd) and endogenous production (EGP) of glucose during the night. On separate
      days at bedtime (2200 h), patients received a sc injection of insulin glargine,
      NPH insulin, or saline in a randomized, double-blind fashion. RESULTS: Similar
      doses of both insulins had different metabolic profiles. NPH insulin had a
      greater effect on both Rd and EGP in the night compared with insulin glargine. By
      contrast, in the morning, insulin glargine was more effective, increasing Rd by
      5.8 micromol/kg(-1).min(-1) (95% confidence interval 4.7-6.9) and reducing EGP 
      5.7 (-5.0 to -6.4) compared with NPH insulin. Nearly 80% of the glucose lowering
      effect in the morning was due to insulin glargine's reduction of EGP. Its
      injection was associated with one-third lower morning glucagon levels compared
      with NPH insulin (P = 0.021). CONCLUSION/INTERPRETATION: Nocturnal variations of
      EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting
      glucose levels reported for insulin glargine compared with human NPH insulin.

PMID- 18611976
TI  - Genetic loci linked to pituitary-thyroid axis set points: a genome-wide scan of a
      large twin cohort.
AB  - OBJECTIVE: Previous studies have shown that circulating concentrations of TSH,
      free T4, and free T3 are genetically regulated, but the genes responsible remain
      largely unknown. The aim of this study was to identify genetic loci associated
      with these parameters. DESIGN: We performed a multipoint, nonparametric genome
      wide linkage scan of 613 female dizygotic twin pairs. All subjects were euthyroid
      (TSH 0.4-4.0 mU/liter) with negative thyroid peroxidase antibodies and no history
      of thyroid disease. The genome scan comprised 737 microsatellite markers
      supplemented with dinucleotide markers. Data were analyzed using residualized
      thyroid hormone data after adjustment for age, smoking, and body mass index.
      RESULTS: Multipoint linkage analysis gave linkage peaks for free T4 on chromosome
      14q13 and 18q21 [logarithm of odds (LOD) 2.4-3.2]; TSH on chromosomes 2q36, 4q32,
      and 9q34 (LOD 2.1-3.2); and free T3 on chromosomes 7q36, 8q22, and 18q21 (LOD 2.0
      2.3). CONCLUSIONS: This study has identified eight genomic locations with linkage
      of LOD of 2.0 or greater. These results should enable targeted positional
      candidate and positional cloning studies to advance our understanding of genetic
      control of the pituitary-thyroid axis.

PMID- 18611977
TI  - Lipodystrophy in patients with acromegaly receiving pegvisomant.
AB  - CONTEXT: Pegvisomant, a GH receptor antagonist, suppresses serum IGF-I levels
      into the normal range in more than 95% of patients with acromegaly. Documented
      side effects in the initial registration studies included headache, injection
      site reactions, flu-like syndrome, and reversible elevation of hepatic enzymes.
      OBJECTIVE: We report seven patients with acromegaly treated with pegvisomant who
      developed lipodystrophy at the site of injection (anterior abdominal wall, thigh,
      buttock, and upper arm). This side effect resulted in discontinuation of
      pegvisomant in four patients, with subsequent regression of lipohypertrophy.
      SUBJECTS: Six female and one male patient with acromegaly, aged 24-59 yr, are
      reported. All patients had undergone prior transsphenoidal surgery, and four
      received subsequent radiotherapy. Four patients had been treated with maximal
      doses of somatostatin analogs with partial suppression of IGF-I levels before
      initiation of pegvisomant therapy. Pegvisomant suppressed IGF-I levels into the
      normal range in five of seven subjects, before discontinuation of the drug. Two
      of seven patients received pegvisomant as first-line medical therapy, without
      prior somatostatin analog treatment, and one received combination therapy with a
      long-acting somatostatin analog and weekly pegvisomant injections. One patient
      experienced an erythematous superficial injection-site reaction that responded to
      application of steroid cream before the onset of lipohypertrophy. CONCLUSIONS: We
      report seven patients with acromegaly who developed lipohypertrophy at the
      pegvisomant injection site. Pegvisomant was discontinued due to dissatisfaction
      with lipohypertrophy by four patients. Lipohypertrophy regressed in all patients
      when the medication was discontinued. Lipohypertrophy recurred when two patients
      were rechallenged with pegvisomant. Patients receiving pegvisomant should undergo
      frequent examination of injection sites for lipohypertrophy.

PMID- 18611978
TI  - Estrogen supplementation selectively enhances hypothalamo-pituitary sensitivity
      to ghrelin in postmenopausal women.
AB  - CONTEXT: Sex-steroid hormones amplify pulsatile GH secretion by unknown
      mechanisms. Ghrelin is the most potent natural GH secretagogue discovered to
      date. A plausible unifying postulate is that estradiol (E(2)) enhances
      hypothalamo-pituitary sensitivity to ghrelin (a physiological effect). The
      hypothesis is relevant to understanding the basis of hyposomatotropism in aging
      and other relatively hypogonadal states. OBJECTIVE: Our objective was to test the
      hypothesis that E(2) supplementation potentiates ghrelin's stimulation of
      pulsatile GH secretion. SETTING: The study was conducted at an academic medical
      center. SUBJECTS: Healthy postmenopausal women (n = 20) were included in the
      study. INTERVENTIONS: Separate-day iv infusions of saline vs. five graded doses
      of ghrelin were performed in volunteers prospectively randomly assigned to
      receive (n = 8) or not receive (n = 12) transdermal E(2) for 21 d were performed.
      MEASURES: GH secretion was estimated by deconvolution analysis and abdominal
      visceral fat mass determined by computerized axial tomography were calculated.
      RESULTS: E(2) supplementation augmented ghrelin's stimulation of basal
      (nonpulsatile) GH secretion by 3.6-fold (P = 0.022), increased GH responses to
      low-dose ghrelin by 2.9-fold (P = 0.035), did not alter ghrelin efficacy, and
      elicited more regular patterns of acylated ghrelin concentrations during saline
      infusion (P = 0.033). Abdominal visceral fat negatively determined responses to
      ghrelin (R = -0.346; P < 0.005). CONCLUSIONS: Transdermal E(2) supplementation
      potentiates GH secretion stimulated by physiological but not pharmacological
      concentrations of acylated ghrelin, and concomitantly regularizes patterns of
      bioactive ghrelin secretion in postmenopausal women. Accordingly, the estrogen
      milieu appears to control sensitivity of the hypothalamopituitary unit to
      acylated ghrelin.

PMID- 18611979
TI  - ADVIRC is caused by distinct mutations in BEST1 that alter pre-mRNA splicing.
AB  - Autosomal dominant vitreoretinochoroidopathy (ADVIRC), a retinal dystrophy often
      associated with glaucoma and cataract, forms part of a phenotypic spectrum of
      'bestrophinopathies'. It has been shown previously that ADVIRC results from BEST1
      mutations that cause exon skipping and lead to the production of shortened and
      internally deleted isoforms. This study describes a novel ADVIRC mutation and
      show that it disrupts an exonic splice enhancer (ESE) site, altering the binding
      of a splicing-associated SR protein. As with previous ADVIRC mutations, the novel
      c.704T-->C mutation in exon 6 altered normal splicing in an ex vivo splicing
      assay. Both this and another exon 6 ADVIRC-causing mutation (c.707G-->A) either
      weakened or abolished splicing in an ESE-dependent splice assay compared with a
      nearby exon 6 mutation associated with Best disease (c.703G-->C). Gel shift
      assays were undertaken with RNA oligonucleotides encompassing the ADVIRC and Best
      disease mutations with four of the most commonly investigated SR proteins.
      Although SC35, SRp40 and SRp55 proteins all bound to the wild-type and mutated
      sequences with similar intensities, there was increased binding of ASF/SF2 to the
      two ADVIRC-mutated sequences compared with the wild-type or Best disease-mutated
      sequences. The exon skipping seen for these two exon 6 ADVIRC mutations and their
      affinity for ASF/SF2 suggests that the region encompassing these mutations may
      form part of a CERES (composite exonic regulatory elements of splicing) site.

PMID- 18611980
TI  - Heart-hand syndrome of Slovenian type: a new kind of laminopathy.
AB  - BACKGROUND: Heart-hand syndromes are a heterogeneous group of genetic disorders
      characterised by the association of congenital cardiac disease and limb
      deformities. Laminopathies are a group of diseases caused by mutations in the
      LMNA gene encoding A-type lamins. RESULTS: We report a new LMNA mutation (c.1609
      12T>G, IVS9-12 T>G) that creates a new cryptic splicing site with the retention
      of 11 intronic nucleotides in the mRNA. This LMNA mutation segregates with a new
      type of heart-hand syndrome in a previously reported family suffering from adult
      onset progressive conduction system disease, atrial and ventricular
      tachyarrhythmias, sudden death, dilated cardiomyopathy, and brachydactyly with
      predominant foot involvement. Analysis of the fibroblasts of two affected family
      members identified for the first time a truncated lamin A/C protein resulting
      from the frame shift created by the new splicing site, together with nuclear
      envelope abnormalities confirming that this LMNA mutation is pathogenic.
      CONCLUSIONS: This new heart-hand syndrome should therefore be considered as a new
      kind of laminopathy. As part of laminopathies with heart involvement, patients
      presenting with this phenotype and their relatives are at risk for developing
      sudden cardiac death and should beneficiate from appropriate LMNA genetic
      diagnosis.

PMID- 18611981
TI  - Neurodevelopmental abnormalities associated with severe congenital neutropenia
      due to the R86X mutation in the HAX1 gene.
AB  - OBJECTIVE: Severe congenital neutropenia (SCN), also known as Kostmann syndrome
      (SCN3, OMIM 610738), includes a variety of haematological disorders caused by
      different genetic abnormalities. Mutations in ELA2 are most often the cause in
      autosomal dominant or sporadic forms. Recently, mutations in HAX1 have been
      identified as the cause of some autosomal recessive forms of SCN, including those
      present in the original pedigree first reported by Kostmann. We sought to
      determine the relationship between HAX1 gene mutations and the clinical
      characteristics of Japanese cases of SCN. METHODS: The genes implicated in SCN
      (ELA2, HAX1, Gfi-1, WAS, and P14) were analysed in 18 Japanese patients with SCN.
      The clinical features of these patients were obtained from medical records.
      Immunoblotting of HAX1 was performed on cell extracts from peripheral blood
      leucocytes from patients and/or their parents. RESULTS: We found five patients
      with HAX1 deficiency and 11 patients with mutations in the ELA2 gene. In HAX1
      deficiency, a homozygous single base pair substitution (256C>T), which causes the
      nonsense change R86X, was identified in three affected individuals. Two sibling
      patients showed a compound heterozygous mutation consisting of a single base pair
      substitution (256C>T) and a 59 bp deletion at nucleotides 376-434. There was no
      detectable phenotype in any heterozygous carrier. All patients with HAX1
      deficiency had experienced developmental delay. Three patients carrying R86X also
      suffered from epileptic seizures. In contrast, no SCN patient with heterozygous
      mutations in the ELA2 gene suffered from any neurodevelopmental abnormality.
      CONCLUSIONS: These findings suggest that the R86X mutation in the HAX1 gene is an
      abnormality in Japanese SCN patients with HAX1 deficiency and may lead to
      neurodevelopmental abnormalities and severe myelopoietic defects.

PMID- 18611982
TI  - Pseudomitochondrial genome haunts disease studies.
AB  - The accidental amplification of nuclear mitochondrial pseudogenes (NUMTs) can
      pose a serious problem for mitochondrial disease studies. This report shows that
      the mutation spectrum left by spurious amplification of a NUMT can be detected
      because it usually differs considerably from the authentic natural spectrum. This
      study examined the problem introduced by an ND5 gene NUMT that was recorded in a
      proband with hearing loss and reviews other disease studies erroneously reporting
      NUMT variation as genuine mutations in their patients. NUMTs can emerge in
      population genetic studies, as exemplified here by cases in this study and from
      published sources. Appropriate database searches and a phylogenetic approach can
      prevent hasty claims for novelty of mitochondrial DNA (mtDNA) variants
      inadvertently derived from NUMTs and help to direct investigators to the real
      source.

PMID- 18611983
TI  - Biallelic loss of function of the promyelocytic leukaemia zinc finger (PLZF) gene
      causes severe skeletal defects and genital hypoplasia.
AB  - BACKGROUND: Deletions of 11q23 are associated with mental retardation,
      craniofacial dysmorphism, microcephaly and short stature. We present a patient
      with similar clinical findings, in addition to absence of the thumbs, hypoplasia
      of the radii and ulnae, additional vertebrae and ribs, retarded bone age and
      genital hypoplasia. METHODS: Genomic DNA from the patient was screened for
      chromosomal imbalances by array-based comparative genomic hybridisation. DNA
      sequence analyses and reporter gene assays were performed in order to identify
      candidate gene mutations. RESULTS: The patient has an approximately 8 Mbp de novo
      deletion on the paternal chromosome 11, which includes the promyelocytic
      leukaemia zinc-finger gene (PLZF, ZBTB16; OMIM 176797). The maternal PLZF allele
      harbours a recessive missense mutation (c.1849A-->G), which leads to the
      substitution of a highly conserved methionine by valine (p.Met617Val) within a
      zinc-finger motif. Taking into account specific alpha-helical propensities of Val
      and Met, this mutation is likely to destabilise the alpha helix of the zinc
      finger that forms the contact with the DNA duplex, thus affecting the biological
      function as shown by reporter-gene assays. DISCUSSION: The PLZF gene is one of
      five partners fused to the retinoic acid receptor alpha in acute promyelocytic
      leukaemia. We describe the first patient, to our knowledge, with a germline
      mutation of PLZF. Our findings as well as observations in Plzf-deficient mice
      indicate that PLZF is a key regulator of skeletal and male germline development.
      Furthermore, this case highlights the importance of searching for a recessive
      mutation on the non-deleted chromosome in patients with a microdeletion and
      atypical clinical findings.

PMID- 18611984
TI  - The CTG repeat expansion size correlates with the splicing defects observed in
      muscles from myotonic dystrophy type 1 patients.
AB  - BACKGROUND: Myotonic dystrophy type 1 is caused by an unstable (CTG)n repetition
      located in the 3'UTR of the DM protein kinase gene (DMPK). Untranslated expanded
      DMPK transcripts are retained in ribonuclear foci which sequester CUG-binding
      proteins essential for the maturation of pre-mRNAs. AIM: To investigate the
      effects of CTG expansion length on three molecular parameters associated with the
      DM1 muscle pathology: (1) the expression level of the DMPK gene; (2) the degree
      of splicing misregulation; and (3) the number of ribonuclear foci. METHODS:
      Splicing analysis of the IR, MBNL1, c-TNT and CLCN1 genes, RNA-FISH experiments
      and determination of the DMPK expression on muscle samples from DM1 patients with
      an expansion below 500 repetitions (n = 6), DM1 patients carrying a mutation
      above 1000 CTGs (n = 6), and from controls (n = 6). RESULTS: The level of
      aberrant splicing of the IR, MBNL1, c-TNT and CLCN1 genes is different between
      the two groups of DM1 muscle samples and correlates with the CTG repeat length.
      RNA-FISH analysis revealed that the number of ribonuclear foci in DM1 muscle
      sections increases in patients with a higher (CTG)n number. No relationships were
      found between the expression level of the DMPK gene transcript and average
      expansion sizes. CONCLUSION: The CTG repeat length plays a key role in the extent
      of splicing misregulation and foci formation, thus providing a useful link
      between the genotype and the molecular cellular phenotype in DM1.

PMID- 18611985
TI  - Glucocorticoids induce an activated, anti-inflammatory monocyte subset in mice
      that resembles myeloid-derived suppressor cells.
AB  - Glucocorticoids (GC) are still the most widely used immunosuppressive agents in
      clinical medicine. Surprisingly, little is known about the mechanisms of GC
      action on monocytes, although these cells exert pro- and anti-inflammatory
      effects. We have shown recently that GC induce a specific monocyte phenotype with
      anti-inflammatory properties in humans. We now investigated whether this also
      applies for the murine system and how this subset would relate to recently
      defined murine subtypes. After treatment with dexamethasone for 48 h, monocytes
      up-regulated scavenger receptor CD163 and Gr-1, down-regulated CX(3)CR1, and
      shared with human GC-treated monocytes functional features such as low
      adhesiveness but high migratory capacity. They specifically up-regulated anti
      inflammatory IL-10, but not TGF-beta, and in contrast to their human
      counterparts, they down-regulated IL-6. Although GC-induced monocytes down
      regulated CX(3)CR1, a distinctive marker for classical/proinflammatory human and
      murine monocytes (CX(3)CR1(lo)CCR2(+)Ly6C(hi)), they differed from this
      physiologically occurring subset, as they remained Ly6C(med) and unactivated
      (CD62 ligand(++)). In addition to their immunosuppressive effects, they were
      CD11b(+)Gr-1(+) and expressed the IL-4Ralpha chain (CD124), a recently described,
      signature molecule of tumor-induced myeloid-derived suppressor cells (MDSC). We
      therefore generated murine MDSC in B16 melanoma-bearing mice and indeed found
      parallel up-regulation of CD11b(+)Gr-1(+) and CD124 on GC-induced monocytes and
      MDSC. These data allow us to speculate that the GC-induced subtype shares with
      inflammatory monocytes the ability to migrate quickly into inflamed tissue, where
      they, however, exert anti-inflammatory effects and that similarities between GC
      induced monocytes and MDSC may be involved in progression of some tumors observed
      in patients chronically treated with GC.

PMID- 18611986
TI  - Induction of human CD4+ regulatory T cells by mycophenolic acid-treated dendritic
      cells.
AB  - Depending on their degree of maturation, costimulatory molecule expression, and
      cytokine secretion, dendritic cells (DC) can induce immunity or tolerance. DC
      treated with mycophenolic acid during their maturation (MPA-DC) have a regulatory
      phenotype and may therefore provide a new approach to induce allograft tolerance.
      Purified CD4(+) T cells stimulated in a human in vitro model of mixed culture by
      allogeneic MPA-DC displayed much weaker proliferation than T cells activated by
      mature DC and were anergic. This hyporesponsiveness was alloantigen-specific.
      Interestingly, T cells stimulated by MPA-DC during long-term coculture in four 7
      day cycles displayed potent, suppressive activity, as revealed by marked
      inhibition of the proliferation of naive and preactivated control T cells. These
      regulatory T cells (Tregs) appeared to have antigen specificity and were contact
      dependent. Tregs induced by MPA-DC were CD25(+)glucocorticoid-induced TNFR(+)CTLA
      4(+)CD95(+), secreted IL-5 and large amounts of IL-10 and TGF-beta, and displayed
      enhanced forkhead box p3 expression. These results obtained in vitro demonstrate
      that human MPA-DC can induce allospecific Tregs that may be exploited in cell
      therapy to induce allograft tolerance.

PMID- 18611987
TI  - CCR5 expression on macrophages/microglia is associated with early remyelination
      in multiple sclerosis lesions.
AB  - Remyelination in multiple sclerosis (MS) occurs spontaneously and extensively.
      The underlying mechanisms, however, are only partly understood. Findings in
      experimental animal settings suggest that inflammation promotes remyelination and
      repair. Here, we characterized the chemokine receptor expression profiles of
      macrophages/microglia in early remyelinating and completely remyelinated lesions
      compared with active demyelinating and inactive demyelinated MS lesions obtained
      in the early disease course. Biopsy material consisting of 16 MS cases was
      available for this study. We found that macrophages/microglia within early
      remyelinating lesions expressed predominantly CCR5. Our findings implicate a
      possible role of CCR5(+) cells in initiating remyelination.

PMID- 18611988
TI  - Multiple sclerosis: glatiramer acetate induces anti-inflammatory T cells in the
      cerebrospinal fluid.
AB  - Glatiramer acetate (GA) is believed to induce GA-reactive T cells that secrete
      anti-inflammatory cytokines at the site of inflammation in multiple sclerosis
      (MS). However, GA-reactive T cells have not been established from the intrathecal
      compartment of MS patients, and intrathecal T cells may differ from T cells in
      blood. Here, we compared the phenotype of GA-reactive T cells from the
      cerebrospinal fluid (CSF) and blood of five MS patients treated with GA for 3-36
      months, and in three of these patients also before treatment. From the CSF of
      these patients, all 22 T cell lines generated before and all 38 T cell lines
      generated during treatment were GA-reactive. GA treatment induced a more
      pronounced anti-inflammatory profile of GA-reactive T cell lines from CSF than
      from blood. While GA-reactive T cell clones from CSF were restricted by either
      human leukocyte antigen (HLA) -DR or HLA-DP, only HLA-DR restricted GA-reactive T
      cell clones were detected in blood. No cross reactivity with myelin proteins was
      detected in GA-reactive T cell lines or clones from CSF. These results suggest
      that a selected subset of GA-reactive T cells are present in the intrathecal
      compartment, and support an anti-inflammatory mechanism of action for GA.

PMID- 18611989
TI  - Persistent T1 hypointensity as an MRI marker for treatment efficacy in multiple
      sclerosis.
AB  - BACKGROUND: MRI is often used as primary outcome measure in phase II clinical
      trials in multiple sclerosis (MS). Since persistent T1 hypointense lesions are a
      surrogate parameter for axonal damage and demyelination, they may serve as a
      marker for monitoring the efficacy of neuroprotective drugs. At present, a power
      analysis using black hole (BH) evolution as primary outcome measure has not been
      performed. OBJECTIVE: To assess the feasibility of using BH evolution on serial
      brain MR images as primary outcome measure in proof of concept studies in MS.
      METHODS: MRI-data obtained from 169 active RRMS patients were analysed for BH
      evolution by determining the cumulative number of contrast enhancing lesions
      (CEL) evolving into a persistent black hole (PBH) after 3 months. With a
      parametric simulation procedure, based on a statistical distribution fitting the
      data, sample sizes were calculated. RESULTS: 21.2% of the total number of CELs
      observed during the study period evolved into a PBH. Ring enhancing lesions
      evolved most frequently into a PBH (59.4%), followed by lesions larger than 10 mm
      (57.4%) and periventricular CELs (30.6%). The simulation procedure, based on the
      statistical negative binomial (NB) model resulted in a sample sizes between 200
      subjects and 30 subjects per arm, for treatment effects ranging from 50% to 90%
      reduction of the number of CELs evolving into a PBH, respectively. CONCLUSION: To
      perform a MRI monitored phase II clinical trial with a feasible sample size,
      using the evolution of CELs into PBHs as primary outcome parameter, a potent drug
      is required to obtain sufficient power.

PMID- 18611990
TI  - Atrophy in white matter fiber tracts in multiple sclerosis is not dependent on
      tract length or local white matter lesions.
AB  - The pathogenesis of tissue injury outside the white matter (WM) plaques of
      multiple sclerosis (MS) has not yet been clearly defined. To better understand
      the pathogenesis of this injury and the associated atrophy, we investigated
      volume loss over time in 20 WM fiber tracts. We defined two main aims: (1) to
      examine whether certain fiber tracts were more prone to atrophy, and to test the
      possible relation of tract atrophy to tract length and selected MS-specific
      variables; and (2) to investigate the possible relation of atrophy to lesion load
      (whole brain and in the specific tract). Local volume change was assessed between
      two distant time points for each MS patient studied. Fiber tracts were segmented
      automatically using a tractography-based atlas. Results demonstrate volume loss
      in all fiber tracts. The uncinate fasciculus and anterior-thalamic radiation had
      the greatest yearly percentage atrophy. Disease type, duration, median expanded
      disability status scale, total lesion load, and gender exhibited significant
      effects on atrophy in at least one tract. Together, these data are more
      consistent with a pathogenesis for the degeneration related to diffuse
      inflammation rather than the secondary effects of focal lesions.

PMID- 18611991
TI  - Absence of diffuse cervical cord tissue damage in early, non-disabling relapsing
      remitting MS: a preliminary study.
AB  - BACKGROUND: Magnetization transfer (MT) magnetic resonance imaging (MRI) can
      provide quantitative information about the severity of tissue damage in the
      cervical cord of patients with multiple sclerosis (MS). MT MRI-derived measures
      of cord damage are correlated with the severity of disease-related locomotor
      disability. OBJECTIVES: The objective of this study was to investigate whether MT
      MRI-detectable cervical cord damage is present in early relapsing-remitting (RR)
      MS. SUBJECTS AND METHODS: We studied 23 patients with 'early' RR MS (i.e., with a
      disease duration shorter than 5 years) and 10 age-matched healthy control
      subjects. During a single session, the following sequences were acquired using a
      1.5 T scanner: (a) brain dual-echo turbo spin echo; (b) cervical cord fast short
      tau inversion recovery; (c) cervical cord gradient echo, without and with MT
      pulse. Brain T2 lesion volume was measured. Cervical cord lesions were counted
      and normalized histograms of cord MT ratio (MTR) were produced. RESULTS: One or
      more cervical cord lesions were found in nine patients (39%). The average cord
      MTR and the mean histogram peak height values did not differ between patients and
      controls. There was no significant correlation between brain T2 lesion volume and
      cervical cord MTR histogram-derived metrics. CONCLUSIONS: Cervical cord tissue
      damage seems to be limited to macroscopic lesions in patients with early, non
      disabling RR MS. Longitudinal studies are warranted to define the dynamics of MS
      related cord damage accumulation over time later on in the course of the disease.

PMID- 18611992
TI  - Burden of deep vein thrombosis in the outpatient setting following major
      orthopedic surgery.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a known complication of major
      orthopedic surgery (MOS) with important clinical and economic consequences.
      Recently published orthopedic guidelines have focused on prevention of pulmonary
      embolism as a primary outcome, but deep vein thrombosis (DVT) occurrence should
      not be readily dismissed. OBJECTIVE: To describe the burden of DVT following
      hospital discharge for MOS by assessing the impact of DVT on costs and resource
      utilization from the third-party payer perspective. METHODS: Retrospective
      analysis used outpatient medical and pharmacy data from the PharMetrics Patient
      Centric Database (January 1, 2002-March 31, 2006). Patients 18 years of age or
      older with a record of MOS were eligible for inclusion. Included patients were
      stratified based on the presence of a DVT during the first month after hospital
      discharge. Characteristics of the samples were described. The impact of DVT on
      total 6-month costs and resource utilization (readmissions, outpatient, emergency
      department visits) was assessed through statistical models. RESULTS: Of the
      32,899 patients in the analysis, 1221 (3.71%) had a record of DVT during the
      first month following discharge for MOS. Compared with patients who did not
      develop DVT, patients who developed DVT postdischarge were slightly older (56.5
      vs 55.8 y; p = 0.0127), had a higher occurrence of prior VTE (26.2% vs 3.4%; p <
      0.0001), and had undergone recent surgical procedures other than MOS (73.0% vs
      69.6%; p = 0.0116). After controlling for potential confounders, DVT was
      associated with a 22% and 74% increase in the average number of expected
      outpatient and emergency department visits, respectively, during the 6-month
      postdischarge period but did not significantly impact the number of readmissions.
      Furthermore, total 6-month costs were significantly higher for patients who
      developed DVT, with an incremental increase of over $2000. CONCLUSIONS: The
      burden of DVT following hospital discharge for MOS is substantial. Specifically,
      DVT increases total costs and outpatient and emergency department visits.

PMID- 18611993
TI  - First Vice Presidential address: practice management.

PMID- 18611994
TI  - The urgency of surgical debridement in the management of open fractures.
AB  - Emergent debridement of open fractures within 6 hours of injury has long been
      considered to be critical to prevention of infection. The basis for this mandate
      is unclear, however. In clinical practice, physiologic and logistical challenges
      frequently limit the degree to which such emergent surgical care can effectively
      be rendered. Furthermore, concerns exist that quality of care might be improved
      when services are performed during normal working hours. The current literature
      suggests no obvious advantage to performing surgical debridement within 6 hours
      after injury versus doing so between 6 and 24 hours after injury. The effect of
      delays >24 hours is unclear. Further research in this area would be helpful, but
      development of definitive level I evidence seems unlikely. Surgical debridement
      of open fractures should be accomplished urgently, as soon as the patient's
      physiologic condition permits and as soon as appropriate resources are available
      to safely perform the procedure.

PMID- 18611995
TI  - Controversies in soft-tissue anterior cruciate ligament reconstruction: grafts,
      bundles, tunnels, fixation, and harvest.
AB  - Increased stability has been reported with both autografts and allografts for
      anterior cruciate ligament (ACL) reconstruction. However, meta-analysis has shown
      significantly lower overall knee stability rates and more than double the
      abnormal stability rate with allografts. Some issues surrounding allograft
      sterilization (ie, risk of disease transmission) are unresolved, and cost is also
      a concern. Single-bundle ACL reconstruction can produce high stability rates when
      tunnels are properly placed, but there is evidence that double-bundle repair may
      offer greater rotatory stability. Cortical fixation has been associated with
      increased stability owing to the high stiffness of cortical bone. Anterior and
      posterior approaches are both recommended. The controversy related to single
      bundle versus double-bundle ACL reconstruction remains unresolved.

PMID- 18611996
TI  - Chronic glenohumeral dislocation.
AB  - The evaluation and management of chronic glenohumeral dislocations can be
      challenging. By definition, chronic glenohumeral dislocations represent injuries
      that were not identified at the time of injury. Therefore, the primary goal is to
      avoid circumstances in which these injuries are not recognized. This includes
      undertaking a comprehensive clinical evaluation as well as appropriate imaging
      studies to understand the pathoanatomic changes-specifically, the humeral head
      impression fracture and any associated glenoid changes. The size of the
      impression fracture and duration of the dislocation are important factors in
      determining the appropriate treatment approach. Satisfactory outcomes can be
      achieved by using a variety of techniques, including open reduction combined with
      tendon transfers, allograft reconstruction, disimpaction and bone grafting and
      prosthetic replacement. Equally important, however, is recognizing patients in
      whom successful outcomes can be achieved with nonsurgical management.

PMID- 18611997
TI  - Adult-acquired flatfoot deformity.
AB  - Originally known as posterior tibial tendon dysfunction or insufficiency, adult
      acquired flatfoot deformity encompasses a wide range of deformities. These
      deformities vary in location, severity, and rate of progression. Establishing a
      diagnosis as early as possible is one of the most important factors in treatment.
      Prompt early, aggressive nonsurgical management is important. A patient in whom
      such treatment fails should strongly consider surgical correction to avoid
      worsening of the deformity. In all four stages of deformity, the goal of surgery
      is to achieve proper alignment and maintain as much flexibility as possible in
      the foot and ankle complex. However, controversy remains as to how to manage
      flexible deformities, especially those that are severe.

PMID- 18611998
TI  - Syringomyelia-associated scoliosis with and without the Chiari I malformation.
AB  - Although there may be a hereditary component to true idiopathic scoliosis, the
      condition has no known cause and is not associated with dysraphism. However,
      scoliosis with an associated syrinx, with or without the Chiari I malformation,
      sometimes presents as an idiopathic-type curve. Physical examination findings and
      subtle clues on diagnostic imaging may help the orthopaedic surgeon diagnose
      scoliosis associated with syringomyelia. Examination findings include asymmetric
      reflexes and presentation at ages younger than those of patients who present with
      adolescent idiopathic curves (i.e., 10 to 14 years). Radiologic findings include
      kyphosis at the apex of the curve. Indications for surgical decompression include
      progressive neurologic deficits, weakness, pain, and progressive curves. Most
      orthopaedic surgeons agree that a syrinx should be evaluated neurosurgically
      before any planned spinal arthrodesis to decrease the risk of neurologic injury
      connected with surgical correction. The indications for arthrodesis in these
      patients compared with those with idiopathic curves are evolving.

PMID- 18611999
TI  - Basal joint arthritis of the thumb.
AB  - The carpometacarpal joint of the thumb is the second most common site of
      arthritis in the hand. Patients in whom conservative treatment fails benefit from
      surgical intervention, although no consensus exists as to the best method to
      provide maximum pain relief and functional outcomes. The pathophysiology of
      carpometacarpal arthritis is loss of the integrity of the palmar oblique
      ligament, which allows for dorsal subluxation of the metacarpal on the trapezium.
      Most treatments revolve around resection or replacement of the arthritic
      carpometacarpal joint and restoration of the palmar oblique ligament. A critical
      appraisal of the current evidence-based research offers no guidance in treatment
      in the early stages of carpometacarpal arthritis; however, several evidence-based
      studies exist for more advanced stages. Although these studies exhibit
      limitations in regard to validated outcomes, power analysis, and blinded
      assessment, their conclusions question the clinical benefits of ligament
      reconstruction and tendon interposition. Further research is needed to delineate
      the best treatment of early stages of arthritis as well as the clinical
      significance of metacarpal subluxation and subsidence. Further, a standardized
      set of outcome tools is needed for the interpretation and comparison of data in
      regard to clinical outcomes.

PMID- 18612000
TI  - Thoracolumbar fractures: anterior decompression and interbody fusion.

PMID- 18612002
TI  - How prevalent are implant wear and osteolysis, and how has the scope of
      osteolysis changed since 2000?
AB  - Although the incidence of failures resulting from wear-related osteolysis and
      associated severe bone defects are expected to diminish with important advances
      in polyethylene manufacturing and processing, alternative bearing surfaces,
      implant design, and revision techniques, current failures still reflect concerns
      regarding earlier ultra-high-molecular-weight polyethylene sterilization and
      degradation. Clinical experience before the year 2000 included rates of wear and
      osteolysis from 10% to as high as 70% at 7- to 14-year follow-up. With recent
      advances, early clinical results are encouraging, demonstrating 50% to 81%
      decreases in radiographic wear rates. These improvements should eventually reduce
      the burden of future revision hip and knee surgery. However, the long-term in
      vivo durability of total hip arthroplasties using these alternative materials and
      bearing couples has not yet been well established, and considerably fewer
      clinical data are available for other types of joint arthroplasties, such as
      total knee arthroplasty.

PMID- 18612003
TI  - What design factors influence wear behavior at the bearing surfaces in total
      joint replacements?
AB  - Bearing surface wear in total joint replacements arises from local stresses that
      exceed the mechanical strength of the articulating materials. Because both the
      tensile/compressive principal stresses and maximum shear stress near the bearing
      surface increase when contact stresses increase, minimizing contact stresses has
      been a central design goal, especially in total knees. Wear rates increase with
      factors such as increased sliding distance in metal-on-polyethylene bearings, or
      suboptimal fluid film lubrication in the case of hard-on-hard total hip implants.
      These factors in turn depend directly on implant design. Advanced preclinical
      assessment technologies such as laboratory physical simulators and finite element
      analyses have provided means by which the dependence of wear rate on mechanical
      design factors can be quantified. However, untoward complexities occurring in
      vivo, such as impingement or third-body challenge, can appreciably compromise
      wear performance even for implants that are well-designed in terms of bearing
      surface stress minimization.

PMID- 18612004
TI  - How have new designs and new types of joint replacement influenced wear behavior?
AB  - As the principles of joint arthroplasty become increasingly refined and more
      widely established, new designs are being developed that require careful
      evaluation for their propensity to generate wear debris in vivo. In the past
      several years, new designs intended to improve clinical performance have emerged
      in both total knee replacement and total spinal disk replacement. Advances in
      these types of implants have the potential for major clinical impact in the
      coming decade, due to the large number of patients seeking treatment of knee
      arthritis as well as back pain, neck pain, and radiculopathy.

PMID- 18612005
TI  - How have wear testing and joint simulator studies helped to discriminate among
      materials and designs?
AB  - Historically, hip joint simulators most often have been used to model wear of a
      bearing surface against a bearing surface. These simulators have provided highly
      accurate predictions of the in vivo wear of a broad spectrum of bearing
      materials, including cross-linked polyethylenes, metal-on-metal, ceramic-on
      ceramic, and others in development. In recent years, more severe conditions have
      been successfully modeled, including jogging, stair climbing, ball-cup micro
      separation, third-body abrasion, and neck-socket impingement. These tests have
      served to identify improved materials and to eliminate some with inadequate wear
      resistance prior to their clinical use. Simulation of the knee joint is
      inherently more complex than it is for the hip. It is more difficult to compare
      the results of laboratory tests with actual clinical performance, due to the lack
      of accurate in vivo measures of wear. Nevertheless, knee simulators, based on
      force control or motion control, have successfully reproduced the type of surface
      damage that occurs in vivo (eg, burnishing, scratching, pitting) as well as the
      size and shapes of the resultant wear particles. Knee simulators have been used
      to compare molded versus machined polyethylene components, highly cross-linked
      polyethylenes, fixed versus mobile bearings, and oxidized zirconia and other
      materials, under optimal conditions as well as more severe wear modes, such as
      malalignment, higher loading and activity levels, and third-body roughening.

PMID- 18612007
TI  - Orthopaedic joint devices: the FDA's short answers to your questions.
AB  - This article briefly describes the US Food and Drug Administration regulatory
      process for medical devices, focusing on orthopaedic joint device examples. The
      mission of the Center for Devices and Radiological Health is to promote and
      protect the health of the public by ensuring that the medical devices that reach
      US consumers are safe and effective for their intended function. A question and
      answer section is included as a reference guide for the orthopaedic community to
      broadly address some common issues related to orthopaedic device constructs, such
      as hybridization of joint systems, labeling claims, modifications to ultra-high
      molecular-weight polyethylene sought by manufacturers to minimize wear and
      osteolysis, combination products, and the responsibilities of an orthopaedic
      surgeon. The FDA relies on accurate scientific evidence and regulatory science to
      determine the safety and effectiveness of orthopaedic joint devices.

PMID- 18612008
TI  - How are wear-related problems diagnosed and what forms of surveillance are
      necessary?
AB  - Prospective, randomized clinical wear studies have shown significant wear
      reduction when highly cross-linked, e-beamed, melted polyethylene was compared
      with conventional polyethylene sterilized by gamma irradiation in air. More
      complete assessment of wear-induced osteolysis in the general total hip
      arthroplasty patient population must rely on registries with follow-up of large
      populations of patients through radiographic evaluation of wear-related factors,
      such as suboptimal placement of the implant components, osteolytic defects, and
      aseptic loosening. Follow-up radiographs should be obtained in the early
      postoperative period and at 1, 5, and 10 years postoperatively, and then every 1
      to 5 years, thereafter depending on radiographic findings of osteolysis and its
      progression. When pathologic findings are present, further examinations, such as
      oblique Judet views and magnetic resonance imaging (MRI) with artifact
      minimization should be considered to provide a better determination of the extent
      of the osteolysis. Because conventional radiographs underestimate the prevalence
      and extent of osteolysis in many instances, diagnosis and surveillance should be
      performed with radiographic edge detection, spiral computed tomography (CT), MRI,
      radiostereometric analysis, and quantitation of wear and osteolysis, including
      bone and soft-tissue lesions. Helical CT has demonstrated excellent specificity
      in identifying and quantifying the extent of osteolysis. MRI can more accurately
      localize both osseous and soft-tissue particulate disease, and detect granuloma
      and compression on adjacent nerves and vessels.

PMID- 18612009
TI  - What are the guidelines for the surgical and nonsurgical treatment of
      periprosthetic osteolysis?
AB  - Periprosthetic osteolysis is most often diagnosed by plain radiographs. Because
      these radiographs routinely underestimate the extent of the lesion, three
      dimensional imaging should be used early in the evaluation process to confirm the
      presenting extent of disease. If the osteolytic process is asymptomatic,
      scheduled regular follow-up should be instituted until the lesion can be
      confirmed to be stable or until the decision is made to proceed with surgery.
      Nonsurgical management with pharmacologic agents has not proved to be effective.
      If surgery is contemplated, a three-dimensional evaluation with magnetic
      resonance imaging or helical computed tomography can assist in preoperative
      planning. Surgical intervention requires complete debridement of the lesional
      membrane and removal of the wear-generator--with or without component removal and
      with or without bone grafting, depending on the individual circumstances. A
      standardized follow-up evaluation mechanism for all patients should be a part of
      total joint arthroplasty management.

PMID- 18612010
TI  - What is the outcome of treatment for osteolysis?
AB  - Periprosthetic osteolysis secondary to wear-induced particle generation is a
      common long-term complication of hip and knee replacement and frequently results
      in the need for revision surgery. Management of significant bone defects remains
      a surgical challenge. Surgical intervention must address the wear particle
      generator (usually, but not always, the bearing surface), the osteolytic defects,
      and implant-related issues, primarily fixation and alignment. Indications for
      surgical intervention in the absence of loosening and pain are not well
      established. In general, patient age and activity level, the location and size of
      the osteolytic defect, and the clinical record of the implant system will dictate
      treatment choices.

PMID- 18612011
TI  - How have alternative bearings (such as metal-on-metal, highly cross-linked
      polyethylene, and ceramic-on-ceramic) affected the prevention and treatment of
      osteolysis?
AB  - Osteolysis is a multifactorial process dependent on surgical technique, implant
      design, patient factors, and material composition. Alternative bearing surfaces,
      such as highly cross-linked polyethylene, ceramic-on-ceramic, and metal-on-metal
      articular surfaces, have been introduced in an attempt to reduce wear and
      osteolysis following total hip arthroplasty. Intermediate-term follow-up data
      available suggest that the prevalence and severity of osteolysis may be reduced
      with these materials compared with conventional metal-on-polyethylene bearing
      surface couples. However, long-term data are presently unavailable; the future
      performance of these bearings awaits clinical validation.

PMID- 18612014
TI  - How has the biologic reaction to wear particles changed with newer bearing
      surfaces?
AB  - Orthopaedic surgeons have new tools that address the problem of aseptic loosening
      and osteolysis, and these tools are now in widespread clinical use. Hard-on-hard
      bearing couples as well as metal-on-highly cross-linked polyethylene bearing
      couples have lower volumetric wear rates and represent promising solutions to
      reduce the prevalence of osteolysis and aseptic loosening in total joint
      arthroplasty. Volumetric wear rates alone, however, do not completely predict the
      osteolytic potential that is also a function of particle composition, size,
      morphology, and a number of other particle characteristics. Host factors,
      including differing innate reactivities to wear products and adaptive immune
      responses, remain important but incompletely defined. Although the toxicologic
      significance of local and systemic elevations in metal ions has not been
      definitively established, monitoring patients with metal-on-metal bearings with
      serum metal ion levels can be useful to determine the state of the bearing.
      Furthermore, optimization of these bearing systems to further diminish wear and
      corrosion would be highly desirable.

PMID- 18612013
TI  - What are the local and systemic biologic reactions and mediators to wear debris,
      and what host factors determine or modulate the biologic response to wear
      particles?
AB  - New clinical and basic science data on the cellular and molecular mechanisms by
      which wear particles stimulate the host inflammatory response have provided
      deeper insight into the pathophysiology of periprosthetic bone loss. Interactions
      among wear particles, macrophages, osteoblasts, bone marrow-derived mesenchymal
      stem cells, fibroblasts, endothelial cells, and T cells contribute to the
      production of pro-inflammatory and pro-osteoclastogenic cytokines such as TNF
      alpha, RANKL, M-SCF, PGE2, IL-1, IL-6, and IL-8. These cytokines not only promote
      osteoclastogenesis but interfere with osteogenesis led by osteoprogenitor cells.
      Recent studies indicate that genetic variations in TNF-alpha, IL-1, and FRZB can
      result in subtle changes in gene function, giving rise to altered susceptibility
      or severity for periprosthetic inflammation and bone loss. Continuing research on
      the biologic effects and mechanisms of action of wear particles will provide a
      rational basis for the development of novel and effective ways of diagnosis,
      prevention, and treatment of periprosthetic inflammatory bone loss.

PMID- 18612015
TI  - What other biologic and mechanical factors might contribute to osteolysis?
AB  - An overwhelming consensus exists that wear particles are the primary driving
      force in aseptic loosening of orthopaedic implants. Nonetheless, considerable
      evidence has emerged demonstrating that various other factors can modulate the
      biologic activity of orthopaedic wear particles. Two of the most studied
      modulating factors are bacterial endotoxins and implant motion.

PMID- 18612016
TI  - What experimental approaches (eg, in vivo, in vitro, tissue retrieval) are
      effective in investigating the biologic effects of particles?
AB  - Understanding the complex cellular and tissue mechanisms and interactions
      resulting in periprosthetic osteolysis requires a number of experimental
      approaches, each of which has its own set of advantages and limitations. In vitro
      models allow for the isolation of individual cell populations and have furthered
      our understanding of particle-cell interactions; however, they are limited
      because they do not mimic the complex tissue environment in which multiple cell
      interactions occur. In vivo animal models investigate the tissue interactions
      associated with periprosthetic osteolysis, but the choice of species and whether
      the implant system is subjected to mechanical load or to unloaded conditions are
      critical in assessing whether these models can be extrapolated to the clinical
      condition. Rigid analysis of retrieved tissue from clinical cases of osteolysis
      offers a different approach to studying the biologic process of osteolysis, but
      it is limited in that the tissue analyzed represents the end-stage of this
      process and, thus, may not reflect this process adequately.

PMID- 18612017
TI  - Are there biological markers of wear?
AB  - Potential systemic markers of implant wear include products of the wear process
      (particles and ions) and mediators of the inflammatory reaction that can be
      induced by wear. Ions from polymers used in arthroplasty are not specific, but
      high metal ion levels may help identify patients with unexpectedly high wear of
      metal-on-metal implants. The kinetics of ion production, transport, and excretion
      are complex, however, so it is currently difficult to interpret the significance
      of mild elevations in metal ions. Indices of bone turnover (eg, collagen
      fragments) and mediators involved in the inflammatory reaction to particles (eg,
      osteoprotegerin, RANKL, interleukins) may be associated with osteolysis, but
      systemic disorders (eg, osteoarthritis) and the use of medications that influence
      bone remodeling limit the predictive value of these analytes with respect to the
      consequences of implant wear. Using genomic and proteomic methods to measure
      multiple analytes offers promise, but the challenge is to identify markers
      specifically associated with wear that are not elevated by other conditions that
      often coexist in this patient population.

PMID- 18612018
TI  - What patient and surgical factors contribute to implant wear and osteolysis in
      total joint arthroplasty?
AB  - Total joint arthroplasty has been a successful operation for decades. Our current
      patients are younger and more active than those in the past. They place higher
      demands on themselves and have expectations commensurate with their lifestyles.
      Time-limited longevity with the large number of anticipated total joint
      replacement procedures and their potential burden to health care is a growing
      concern. In the past two decades, implant wear and osteolysis have been
      identified as major causes for the failure of otherwise well-functioning
      implants. Osteolysis can be divided into several categories: patient-specific,
      implant-specific, and the result of surgical factors. Although these categories
      are interrelated and not mutually exclusive, they enable us to build a framework
      in which to further advance our understanding of osteolysis and apply this
      information in a clinically relevant manner.

PMID- 18612019
TI  - What potential biologic treatments are available for osteolysis?
AB  - The host response to wear debris particles constitutes a major component of
      periprosthetic osteolysis and aseptic loosening. Thus, biologic interventions
      represent a logical approach to prevent this complication of total joint
      replacement. Several major obstacles must be overcome before a therapeutic
      intervention can emerge, most notably the development of a safe and effective
      drug, as well as the development of a quantitative outcome measure that can prove
      efficacy in a relatively small multicenter trial of patients with established
      osteolysis. Research is needed in several areas, including whether a threshold
      phenomenon exists for osteolytic progression, whether anabolic agents
      administered postoperatively can significantly increase osteointegration of the
      implant and reduce the potential for aseptic loosening, and whether RANKL
      antagonists can inhibit the progression of periprosthetic osteolysis. Imaging
      advancements and an osteolysis registry would significantly enhance the potential
      for a successful clinical trial.

PMID- 18612021
TI  - How have new sterilization techniques and new forms of polyethylene influenced
      wear in total joint replacement?
AB  - Polyethylene has undergone many changes over the past several decades, including
      changes in consolidation processes, resin types, sterilization methods,
      packaging, and the extent of cross-linking. We believe that new sterilization
      techniques and forms of polyethylene have generally improved wear performance.
      Polyethylene sterilized without the use of radiation has been shown to have
      relatively high rates of wear in vivo. Ram-extruded polyethylene sterilized via
      gamma irradiation in air has been the most commonly used bearing material in the
      past several decades. Recently, components molded and gamma-sterilized without
      oxygen as well as highly cross-linked material have found increased clinical use.
      Exposure of polyethylene to radiation, either to sterilize it or to intentionally
      cross-link it, has been shown to improve the wear performance of the material.
      Newer second-generation methods of cross-linking polyethylene include the use of
      vitamin E, which quenches free radicals and demonstrates promise in providing low
      wear and desirable mechanical properties.

PMID- 18612022
TI  - How do alternative bearing surfaces influence wear behavior?
AB  - Metal, ceramic, and polyethylene liners represent contemporary bearing choices
      for total joint replacement. Each has limitations in terms of design, sensitivity
      to manufacturing, and surgical placement. With polyethylene, larger femoral heads
      represent a design restriction and a potential wear issue. One side benefit is
      that polyethylene does not click, squeak, or create stripe wear. The attraction
      of hard-on-hard bearings (metal-on-metal, ceramic-on-ceramic) is that their
      typically ultra-low wear alleviates concerns with large femoral head designs.
      However, hard-on-hard bearings produce stripe wear due to the effects of the
      rigid liner edge. Slight subluxation (microseparation) during swing phase of gait
      can result in stripe wear on the ball and liner rim. In addition, high levels of
      implant wear with vertically placed cups can be anticipated. Currently, only
      alumina-on-alumina bearings can claim virtually no biologic risk. Thus, the role
      of laboratory studies is to isolate relevant aspects of performance by cup design
      and to predict the risk-benefit ratios in patients requiring total hip
      replacement.

PMID- 18612023
TI  - How do material properties influence wear and fracture mechanisms?
AB  - The wear and fracture mechanisms of ultra-high-molecular-weight polyethylene
      (UHMWPE) hip and knee implant components are of great interest. The material
      properties of UHMWPE are affected by ionizing radiation as used for sterilization
      and cross-linking. Cross-linking with high-dose irradiation has been shown to
      improve the wear resistance of UHMWPE. However, cross-linking leads to a loss in
      properties such as ductility and resistance to fatigue crack propagation. Highly
      cross-linked UHMWPE may be more susceptible than conventional UHMWPE to fracture
      under severe clinical conditions (eg, impingement). Contemporary hip and knee
      simulator studies provide good information with which new UHMWPE formulations can
      be screened for clinical wear performance. However, comparable methodologies are
      lacking for screening UHMWPEs for fracture resistance. Mechanical tests as well
      as computational material and structural models should be developed to evaluate
      the combined effect of material and geometry (structure) on fracture resistance
      under clinically relevant loading conditions.

PMID- 18612024
TI  - 2007 AAOS/NIH osteolysis and implant wear: biological, biomedical engineering,
      and surgical principles. Introduction.

PMID- 18612025
TI  - Seppo Santavirta: the life and work of an orthopaedic surgeon and scientist. A
      tribute from his friends.

PMID- 18612026
TI  - Palliative care research in the community: it is time to progress this emerging
      field.

PMID- 18612027
TI  - The nature and use of bereavement support services in a hospice setting.
AB  - This study formed part of a larger project designed to evaluate a hospice-based
      bereavement support service in Ireland. It involved a detailed assessment of the
      views of service attenders and non-attenders. A postal survey was administered to
      all bereaved clients who were invited to one or more bereavement support services
      (n = 517). Respondents (n = 243; 47%) completed: 1) a Bereavement Services
      Questionnaire; 2) a measure of grief reaction (TRIG) and 3) a measure of
      religiosity (SCSORF). A total of 243 people (47%) returned completed
      questionnaires, most of whom were satisfied with the service, (although not all
      had attended all elements of the bereavement service). However, a number of
      improvements were emphasised. Several statistically significant differences (P <
      0.05) also emerged between service attenders and non-attenders with respect to
      grief reaction and other key factors (e.g., the age and relationship to the
      deceased). The findings emphasise the needs and views of both attenders and non
      attenders and provide important lessons for the implementation and development of
      hospice-based bereavement support services.

PMID- 18612028
TI  - Good death study of elderly patients with terminal cancer in Taiwan.
AB  - OBJECTIVES: Over half of all terminal cancer patients in Taiwan are 65 or older,
      thus demonstrating the importance of terminal care for elderly people. This study
      investigates the good death status of elderly patients with terminal cancer,
      comparing the differences in the degree of good death among elderly and younger
      groups, and exploring the factors related to the good death score. METHODS: Three
      hundred and sixty-six patients with terminal cancer admitted to a palliative care
      unit were enrolled. Two structured measurements, the good death scale and the
      audit scale for good death services, were used as the instruments in the study.
      RESULTS: The scores of individual items and of the good death scale were
      increased significantly in both elderly (n = 206, 56.3%) and younger (n = 160,
      43.7%) groups from the time of admission to just prior to death. However, the
      elderly group had significantly lower scores in 'awareness' (t = -3.76, P <
      0.001), 'propriety' (t = -2.92, P < 0.01) and 'timeliness' (t = -2.91, P < 0.01)
      than the younger group prior to death. Furthermore, because of a lack of truth
      telling, the elderly group also had significantly lower scores than the younger
      group in both 'respect for autonomy' and 'decision-making participation' (t = 
      2.17, P < 0.05; t = -2.21, P < 0.05, respectively). Multiple regression analysis
      revealed that 'respect for autonomy' (OR = 1.22, 95% CI = 0.76-1.67) and 'verbal
      support '(OR = 0.93, 95% CI = 0.34-1.51) were two independent correlates of the
      good death score in the elderly group. CONCLUSION: The dilemma of truth-telling
      compromises the autonomy of the elderly patients with terminal cancer and
      consequently affects their good death scores. The palliative care team should
      emphasize the issue of truth-telling in the process of caring for terminally ill
      cancer patients, especially elderly patients.

PMID- 18612029
TI  - Differing management of people with advanced cancer and delirium by four sub
      specialties.
AB  - INTRODUCTION: Delirium in advanced cancer is prevalent, with limited prospective
      data to guide management. The aim was to survey current practice of specialists
      using two contrasting cases of delirium in cancer. METHODS: A questionnaire was
      designed to identify investigations and treatment used, in relation to two cases.
      RESULTS: Overall response rate (n = 270) was 30%. Place of care: Only 35% of
      medical oncologists would consider care at home for a patient with reversible
      delirium compared with 66% of other specialists. INVESTIGATIONS: 85% specialists
      would order basic bloods, however, medical oncologists were more likely to use
      oxygen saturation and head computed tomography, psychogeriatricians more likely
      to order thyroid function and palliative medicine specialists less likely to
      order chest X-ray and urine culture. Greater than 40% of specialists would do no
      investigations for terminal delirium. TREATMENT: Medical oncologists use more pre
      emptive therapies and more likely to use a benzodiazepine as agent of choice, and
      Palliative medicine specialists used significantly more neuroleptics to treat
      hypoactive symptoms of delirium. DISCUSSION: The survey emphasise significant
      areas of variability in the management of delirium in advanced cancer.
      Furthermore, evidence to guide management in ways that draw on the strengths and
      knowledge of each specialty is urgently needed.

PMID- 18612030
TI  - Inappropriateness of using opioids for end-stage palliative sedation: a Dutch
      study.
AB  - To be able to distinguish end-stage palliative sedation from euthanasia without
      having to refer to intentions that are difficult to verify, physicians must be
      able to manage palliative sedation appropriately (i.e., see that death is not
      hastened as a result of disproportionate medication). In the present study, we
      assessed whether or not this requirement is met in the Netherlands. We sent a
      retrospective questionnaire to 1,464 medical specialists, general practitioners,
      and nursing home physicians in the Netherlands. Furthermore, we held two sets of
      20 and 22 semi-structured in-depth interviews with general practitioners,
      internists, lung specialists, and nursing home physicians. Although most
      guidelines discourage the administration of opioids alone for purposes of
      palliative sedation, opioids alone were administered for 22% of all the patients
      reported upon. Those physicians who were more experienced, general practitioners,
      and physicians who had consulted a palliative care expert administered only
      opioids significantly less often than the other physicians. The interviewees
      reported difficulties in assessing the appropriateness of medication, feeling
      uncertain about the pharmacokinetics of drugs used in moribund patients. Given
      that no more than 2% of the respondents perceived palliative sedation to be used
      as a form of euthanasia and that the use of opioids alone was not associated with
      shorter survival rates, the inappropriate use of opioids can only be attributed
      to a lack of knowledge or skill and/or a tradition of alleviating refractory
      dyspnoea with the use of opioids and not as an intentional means of hastening
      death.

PMID- 18612031
TI  - The acceptability of an information leaflet explaining cardiopulmonary
      resuscitation policy in the hospice setting: a qualitative study exploring
      patients' views.
AB  - BACKGROUND: Guidelines advise that patients receiving palliative care should be
      given realistic information about cardiopulmonary resuscitation (CPR) and
      encouraged to participate in decisions about this. For many patients attending a
      hospice, CPR is unlikely to be successful because of advanced disease. It is
      difficult to predict which patients would like to discuss CPR and whether such
      discussion might cause distress. AIM: This research set out to determine the
      acceptability and understanding of a patient information leaflet about CPR given
      to inpatients and day-unit patients in one hospice, and to seek patients' views
      on communication about resuscitation. METHODS: Semi-structured interviews were
      carried out with five hospice inpatients and one day-unit patient and analysed
      using interpretative phenomenological analysis for emergent themes. RESULTS AND
      CONCLUSIONS: The leaflet was acceptable to the participants but was interpreted
      in the context of their understanding of their illness and prognosis. The leaflet
      alone is not a reliable method of communicating resuscitation policy and should
      be followed up by the opportunity to ask questions, if the patient wishes. Many
      factors influence patient choices about CPR. Realistic information about
      prognosis and about the risks and harms of CPR would allow patients to make a
      better-informed decision. However, if a patient prefers not to talk about their
      prognosis and end-of-life issues, then this should be respected.

PMID- 18612032
TI  - Developing narrative research in supportive and palliative care: the focus on
      illness narratives.
AB  - The phenomenon of the 'illness narrative' is well-documented, in the last 25
      years, of increasing interest to researchers in health and social sciences.
      Personal stories about the experience of facing the end of life also have an
      established history of particular relevance for palliative care clinicians. In
      this article, we review and describe a range of narrative analysis approaches
      that may be of use in palliative care. In particular, we distinguish between
      qualitative analysis applied to narratives and narrative analysis as a method. We
      discuss the potential benefits and challenges in the use of narrative research
      methods as a means to deepen our understanding of patient, carer and health
      professionals' experience, and to support improvements in end of life care policy
      and practice.

PMID- 18612033
TI  - The response of a Swiss university hospital's palliative care consult team to
      assisted suicide within the institution.
AB  - In January 2006 the Centre Hospitalier Universitaire Vaudois (CHUV), a large
      university hospital in Lausanne, Switzerland, became the first hospital in
      Switzerland to allow assisted suicide (AS) in exceptional cases within its walls.
      However, euthanasia is illegal. This decision has posed several ethical and
      practical dilemmas for the hospital's palliative care consult service. To address
      these, the team embarked on a formal process of open dialogue amongst its members
      with the goal of identifying a collective response and position. This process
      involved meetings every 4 to 6 weeks over the course of 10 months. An iterative
      process unfolded. One of the principal dilemmas relates to finding a balance
      between the team's position against AS and the patient's autonomy and the
      institution's directive. Although all team members expressed opposition to AS,
      there were mixed opinions as to whether or not the team members should be present
      during the act if requested so by patients. Some thought this could be
      misinterpreted as complicity in the act and could send out mixed messages to the
      public and other health professionals about palliative care. Others felt that the
      team's commitment to nonabandonment obliged them to be present even if they did
      not provide the drug or give any advice or assistance. The implications of
      nonabandonment are explored, as are several other questions such as whether or
      not the teams are obliged to provide detailed information on AS when requested by
      patients.

PMID- 18612034
TI  - To replace or not to replace? - Partial coning and a sixth nerve palsy secondary
      due to displacement of a tunnelled intrathecal catheter for pain control.
AB  - We report the displacement of a tunnelled intrathecal catheter causing
      significant cerebrospinal fluid (CSF) leak, resulting in partial coning and a
      sixth nerve palsy. The patient had advanced malignant mesothelioma and all other
      methods of pain control had been unsuccessful. As far as we are aware, there are
      no published reports of early replacement of an intrathecal catheter in patients
      with neurological sequelae. Surgical re-siting of the intrathecal catheter
      produced good pain relief for many months. Doctors involved in the use of
      indwelling intrathecal catheters for pain control must be aware of the risk of
      significant neurological sequelae but should not dismiss re-establishment of
      intrathecal therapy in the presence of significant neurological complications.

PMID- 18612035
TI  - Death during transfer of a palliative care patient.
AB  - This short report illustrates the potential confusion that exists when terminally
      ill patients die during transfer between places of care. The report documents the
      legal requirements necessary if a terminally ill patient dies during transfer and
      raises the debate regarding what policies and practice currently exist, within
      the UK, for transfer of terminally ill patients.

PMID- 18612036
TI  - Successful control of vomiting, due to malignant upper gastrointestinal
      obstruction, by 'blind' percutaneous gastrostomy, in a terminally ill patient.

PMID- 18612037
TI  - How strictly should advance decisions be followed? The patients' opinion.

PMID- 18612038
TI  - Insurance, risk, and magical thinking.
AB  - The possession of an insurance policy may not only affect the severity of a
      potential loss but also its perceived probability. Intuitively, people may feel
      that if they are insured nothing bad is likely to happen, but if they do not have
      insurance they are at greater peril. In Experiment 1, respondents who were
      reminded of their medical insurance felt they were less likely to suffer health
      problems in the future compared to people who were not reminded of their medical
      insurance. In Experiment 2a, participants who were unable to purchase travel
      insurance judged the probability of travel-related calamities higher compared to
      those who were insured. These results were replicated in Experiment 3a in a
      simulation of car accident insurance. The findings are explained in terms of
      intuitive magical thinking, specifically, the negative affective consequences of
      "tempting fate" and the sense of safety afforded by the notion of "being
      covered."

PMID- 18612039
TI  - Cell phones and the measurement of child neglect: the validity of the parent
      child activities interview.
AB  - Two multisite studies were conducted to assess the feasibility of using cell
      phone interviews (the Parent-Child Activities Interview) to learn more about the
      quality of daily parenting among high-risk mothers, including child neglect. In
      Study 1, 45 primiparous teenage mothers with 3- to 9-month-old infants were
      recruited and randomly assigned to two groups: one received frequent cell phone
      interviews and the other group less frequent interviews over their home
      telephone. Relationships among paper-and-pencil surveys of parenting (gathered in
      person) and a Parenting Essentials score (coded from the phone interviews) were
      significantly correlated. In Study 2, adolescent and adult mothers and their
      first-born children ( n = 544) completed 2 observations of parenting in their
      home as well as a series of 3 PCA calls at ages 4 and 8 months. Parenting
      Essentials coded from the interviews were significantly related to observed
      measures of parenting at both time points. The Parent-Child Activities Interview
      shows promise as a reliable and valid measure of parenting, capturing frequent
      and detailed information about daily parenting practices. Cell phones may prove
      useful in intervening with mothers at risk of suboptimal parenting and child
      neglect.

PMID- 18612040
TI  - Substantiation and adverse appeal outcomes: content analysis and testing of
      Drake's harm/evidence model.
AB  - Little is known about the influence of evidentiary and case characteristics on
      adverse appeal outcomes for substantiated cases of maltreatment. This article,
      therefore, reports on a sample of adverse appeal outcomes during a 2-year period.
      Using Drake's Harm/Evidence model to examine the adverse outcomes, the study
      describes differences between substantiated cases that were "modified" versus
      "overturned" during appeal, as well as differences in their evidentiary
      characteristics across different types of maltreatment. Content analysis and
      logistic regression analysis of administrative data were used to predict
      overturned versus modified outcome. Overall, child neglect, substantiated cases
      that did not meet basic evidentiary standards, and cases that were deemed as not
      credible were more likely to be overturned in comparison to being modified. A
      substantiation assessment framework (SAF) is developed and implications of
      Drake's Harm/Evidence model for investigating maltreatment as well as for
      understanding judicial decision making in appealed cases of maltreatment is
      highlighted.

PMID- 18612042
TI  - Effects of oral carbohydrate on autonomic nervous system counterregulatory
      responses during hyperinsulinemic hypoglycemia and euglycemia.
AB  - The effects of oral carbohydrate on modulating counterregulatory responses in
      humans remain undecided. This study's specific aim was to determine the effects
      of oral carbohydrate on autonomic nervous system (ANS) and neuroendocrine
      responses during hyperinsulinemic hypoglycemia and euglycemia. Nineteen healthy
      volunteers were studied during paired, single blind experiments. Nine subjects
      underwent two-step glucose clamps consisting of 60 min of euglycemia (5.0 mmol/l)
      followed by either 15 g of oral carbohydrate (cal) as orange juice or a
      noncaloric control (nocal) and subsequent 90 min of clamped hypoglycemia (2.9
      mmol/l). Ten other subjects underwent two randomized 150-min hyperinsulinemic
      euglycemic clamps with cal or nocal control administered at 60 min. Oral
      carbohydrate initially blunted (P < 0.05) epinephrine, norepinephrine, cortisol,
      glucagon, pancreatic polypeptide, muscle sympathetic nerve activity (MSNA),
      symptom, and systolic blood pressure responses during hypoglycemia. However, by
      the end of 90 min of hypoglycemia, plasma epinephrine and norepinephrine
      responses had rebounded and were increased (P < 0.05) compared with control. MSNA
      and cortisol levels remained suppressed during hypoglycemia (P < 0.05) after cal,
      whereas pancreatic polypeptide, glucagon, symptom, and blood pressure responses
      increased similar to control following initial suppression. Oral carbohydrate had
      no effects on neuroendocrine or ANS responses during hyperinsulinemic euglycemia.
      These results demonstrate that oral carbohydrate can have differential effects on
      the time course of ANS and neuroendocrine responses during hypoglycemia. We
      conclude that gastro-splanchnic-portal sensing of an amount of carbohydrate
      recommended for use in clinical practice for correction of hypoglycemia can have
      widespread and significant effects on central nervous system mediated
      counterregulatory responses in healthy humans.

PMID- 18612043
TI  - Metabolism and synthesis of arginine vasopressin in conscious newborn sheep.
AB  - Arginine vasopressin (AVP) is an important regulator of cardiovascular
      homeostasis in the fetus, but its role after birth is unclear. Although infused
      AVP increases mean arterial pressure (MAP) during the 1st mo after birth, pressor
      responses are unchanged, suggesting that vascular responsiveness is also
      unchanged. Alternatively, this could reflect increases in AVP metabolic clearance
      rate (MCR(AVP)). However, newborn AVP metabolism and synthesis are poorly
      studied. Therefore, we examined the pressor responses to infused AVP and the
      pattern of circulating AVP, AVP production rate (PR(AVP)), and MCR(AVP) in
      conscious newborn sheep (n = 5) at 9-38 days after birth. Basal MAP rose and
      heart rate (HR) fell during the study period (P < or = 0.02), while circulating
      AVP was unchanged (P > 0.1), averaging 3.01 +/- 0.86 pg/ml. Infused AVP elicited
      steady-state responses at 10-40 min, increasing plasma AVP and MAP and decreasing
      HR (P < 0.001). Although pressor responses were unchanged between 9 and 38 days,
      the rise in MAP correlated with increases in plasma AVP (R = 0.47, P = 0.02, n =
      24). MCR(AVP) was unchanged throughout the 1st mo (P > 0.2), averaging 205 +/- 17
      ml.kg(-1).min(-1), and was associated with an elevated PR(AVP), 973 +/- 267
      pg.kg(-1).min(-1), which also was unchanged (P > 0.1). After birth, MCR(AVP) and
      PR(AVP) are elevated, probably accounting for the stable plasma AVP levels. The
      former is also likely to account for the stable pressor responses to infused AVP
      during the 1st mo. The reason for the elevated PR(AVP) is unclear but may relate
      to increases in vascular volume associated with postnatal growth.

PMID- 18612044
TI  - Incretin and islet hormonal responses to fat and protein ingestion in healthy
      men.
AB  - Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide
      (GIP) regulate islet function after carbohydrate ingestion. Whether incretin
      hormones are of importance for islet function after ingestion of noncarbohydrate
      macronutrients is not known. This study therefore examined integrated incretin
      and islet hormone responses to ingestion of pure fat (oleic acid; 0.88 g/kg) or
      protein (milk and egg protein; 2 g/kg) over 5 h in healthy men, aged 20-25 yr
      (n=12); plain water ingestion served as control. Both intact (active) and total
      GLP-1 and GIP levels were determined as was plasma activity of dipeptidyl
      peptidase-4 (DPP-4). Following water ingestion, glucose, insulin, glucagon, GLP
      1, and GIP levels and DPP-4 activity were stable during the 5-h study period.
      Both fat and protein ingestion increased insulin, glucagon, GIP, and GLP-1 levels
      without affecting glucose levels or DPP-4 activity. The GLP-1 responses were
      similar after protein and fat, whereas the early (30 min) GIP response was higher
      after protein than after fat ingestion (P<0.001). This was associated with
      sevenfold higher insulin and glucagon responses compared with fat ingestion (both
      P<0.001). After protein, the early GIP, but not GLP-1, responses correlated to
      insulin (r(2)=0.86; P=0.0001) but not glucagon responses. In contrast, after fat
      ingestion, GLP-1 and GIP did not correlate to islet hormones. We conclude that,
      whereas protein and fat release both incretin and islet hormones, the early GIP
      secretion after protein ingestion may be of primary importance to islet hormone
      secretion.

PMID- 18612041
TI  - Impaired microvascular perfusion: a consequence of vascular dysfunction and a
      potential cause of insulin resistance in muscle.
AB  - Insulin has an exercise-like action to increase microvascular perfusion of
      skeletal muscle and thereby enhance delivery of hormone and nutrient to the
      myocytes. With insulin resistance, insulin's action to increase microvascular
      perfusion is markedly impaired. This review examines the present status of these
      observations and techniques available to measure such changes as well as the
      possible underpinning mechanisms. Low physiological doses of insulin and light
      exercise have been shown to increase microvascular perfusion without increasing
      bulk blood flow. In these circumstances, blood flow is proposed to be redirected
      from the nonnutritive route to the nutritive route with flow becoming dominant in
      the nonnutritive route when insulin resistance has developed. Increased
      vasomotion controlled by vascular smooth muscle may be part of the explanation by
      which insulin mediates an increase in microvascular perfusion, as seen from the
      effects of insulin on both muscle and skin microvascular blood flow. In addition,
      vascular dysfunction appears to be an early development in the onset of insulin
      resistance, with the consequence that impaired glucose delivery, more so than
      insulin delivery, accounts for the diminished glucose uptake by insulin-resistant
      muscle. Regular exercise may prevent and ameliorate insulin resistance by
      increasing "vascular fitness" and thereby recovering insulin-mediated capillary
      recruitment.

PMID- 18612046
TI  - Anti-inflammatory and anti-apoptotic effects of fumonisin B1, an inhibitor of
      ceramide synthase, in a rodent model of splanchnic ischemia and reperfusion
      injury.
AB  - Ceramide is a sphingolipid with potent proinflammatory and proapoptotic
      properties. This study sought to determine whether pharmacological inhibition of
      ceramide biosynthesis in the intestine attenuates pathophysiological sequelae of
      shock induced by splanchnic artery occlusion and reperfusion. Ischemia and
      reperfusion injury was induced in anesthetized rats by clamping both the superior
      mesenteric artery and the celiac artery for 45 min followed by reperfusion.
      Within 6 min after reperfusion, animals developed significant systemic
      hypotension with 100% of the animals dying during the 4-h period of reperfusion.
      In parallel experiments, animals were necropsied after 60 min of reperfusion, and
      the ileum was harvested for histological examination and assessment of
      biochemical changes. Administration of fumonisin B1 (FB1), a competitive and
      reversible inhibitor of ceramide synthase (3 mg/kg, 15 min before reperfusion),
      significantly reduced i) the increased ceramide expression as detected by
      immunohistochemistry; ii) peroxynitrite-mediated protein nitration; iii)
      infiltration of the reperfused intestine with polymorphonuclear neutrophils
      following a decrease in intercellular adhesion molecule-1 expression; iv)
      production of the proinflammatory cytokine tumor necrosis factor-alpha; and v)
      apoptosis in the ileum. Overall, tissue-protective effects were clearly observed
      upon histological examination of the ileum. These beneficial events were
      ultimately linked to decreases in both the development of hypotension and overall
      mortality. These results implicate ceramide as a key signaling molecule in
      splanchnic arterial ischemia and reperfusion-induced shock. The broader
      implications of our results provide a pharmacological rationale for the
      development of inhibitors of ceramide biosynthesis as novel therapeutics for
      ischemia and reperfusion-induced shock of several etiologies.

PMID- 18612047
TI  - The Translational Research Working Group developmental pathways: introduction and
      overview.
AB  - The Translational Research Working Group (TRWG) was created as a national
      initiative to evaluate the current status of the National Cancer Institute's
      investment in translational research and envision its future in an inclusive,
      representative, and transparent manner. To clarify the challenges facing
      translational research and facilitate its deliberations, the TRWG conceptualized
      translational research as a set of developmental processes or pathways focused on
      various clinical goals. Drawing on the collective knowledge of the TRWG members,
      six pathways were derived, with two addressing the development of tools designed
      to characterize an individual's cancer-related health status (biospecimen-based
      and image-based assessment modalities) and four addressing the development of
      interventions intended to change cancer-related health status (drugs or
      biological agents, immune response modifiers, interventive devices, and life
      style alterations). The pathways, which share a number of common structural
      elements, are graphically represented by schematic flowcharts that capture
      relevant contingencies, decision points, and interdependencies. They are
      conceived not as comprehensive descriptions of the corresponding real-world
      processes but as tools designed to serve specific purposes including research
      program management and research project management, coordination of research
      efforts, and professional and lay education and communication. Further
      development of the pathways is encouraged, as is application of the pathway
      concept to translational research on other diseases.

PMID- 18612045
TI  - The glucocorticoid receptor and FOXO1 synergistically activate the skeletal
      muscle atrophy-associated MuRF1 gene.
AB  - The muscle specific ubiquitin E3 ligase MuRF1 has been implicated as a key
      regulator of muscle atrophy under a variety of conditions, such as during
      synthetic glucocorticoid treatment. FOXO class transcription factors have been
      proposed as important regulators of MuRF1 expression, but its regulation by
      glucocorticoids is not well understood. The MuRF1 promoter contains a near
      perfect palindromic glucocorticoid response element (GRE) 200 base pairs upstream
      of the transcription start site. The GRE is highly conserved in the mouse, rat,
      and human genes along with a directly adjacent FOXO binding element (FBE).
      Transient transfection assays in HepG2 cells and C(2)C(12) myotubes demonstrate
      that the MuRF1 promoter is responsive to both the dexamethasone (DEX)-activated
      glucocorticoid receptor (GR) and FOXO1, whereas coexpression of GR and FOXO1
      leads to a dramatic synergistic increase in reporter gene activity. Mutation of
      either the GRE or the FBE significantly impairs activation of the MuRF1 promoter.
      Consistent with these findings, DEX-induced upregulation of MuRF1 is
      significantly attenuated in mice expressing a homodimerization-deficient GR
      despite no effect on the degree of muscle loss in these mice vs. their wild-type
      counterparts. Finally, chromatin immunoprecipitation analysis reveals that both
      GR and FOXO1 bind to the endogenous MuRF1 promoter in C(2)C(12) myotubes, and IGF
      I inhibition of DEX-induced MuRF1 expression correlates with the loss of FOXO1
      binding. These findings present new insights into the role of the GR and FOXO
      family of transcription factors in the transcriptional regulation of the MuRF1
      gene, a direct target of the GR in skeletal muscle.

PMID- 18612048
TI  - Intermittent high glucose concentrations reduce neuronal precursor survival by
      altering the IGF system: the involvement of the neuroprotective factor DHCR24
      (Seladin-1).
AB  - The exposure of neurons to high glucose concentrations is considered a
      determinant of diabetic neuropathy, whereas members of the IGF system are
      neurotropic factors. Here, we investigated the effects of constant and
      intermittent high glucose concentrations on IGF1 and IGF-binding proteins
      (IGFBPs) in human neuroblast long-term cell cultures fetal neuroepithelial cells
      (FNC). These cells express the IGF1 receptor, and express and release in the
      culture medium IGFBP2, IGFBP4, and IGF1. The release of IGF1 was significantly
      increased by 17beta-estradiol (10 nM). IGF1 (100 nM) treatment determined a
      significant increase of IGFBP2 and a decrease of IGFBP4 release. In addition,
      IGF1 (1-100 nM) stimulated FNC cell proliferation in a dose-dependent manner. We
      hypothesized that this effect may be, at least partially, due to IGF1-induced up
      regulation of the expression of the Alzheimer's disease related gene SELADIN-1
      (now known as DHCR24 ), which acts as a pro-survival factor for neuronal cells.
      Conversely, the exposure to intermittent (20/10 mM), but not stable (20 mM), high
      glucose concentrations decreased the release of IGF1 and IGFBP2 in the culture
      medium and inhibited FNC growth by inducing apoptosis. The latter was prevented
      by the addition of IGF1 to the culture medium. Furthermore, high glucose
      concentrations reduced the expression of DHCR24. In conclusion, our results
      indicate for the first time that intermittent high glucose concentrations,
      similar to those observed in poorly controlled diabetic patients, may contribute
      to the development of diabetic neuropathy by interfering with the tropic effects
      exerted by the IGF system, and suggest the involvement of the neuroprotective
      factor DHCR24.

PMID- 18612049
TI  - Role of surgery for optic pathway/hypothalamic astrocytomas in children.
AB  - Optic pathway/hypothalamic pilocytic astrocytomas in children are usually treated
      with chemotherapy following a surgical biopsy. In this report, we retrospectively
      considered the role of surgical intervention. In a series of 25 patients without
      neurofibromatosis type 1, the median age at initial treatment was 3.1 years
      (range, 0-15 years). Twenty cases were verified by histology, and five cases were
      diagnosed by MRI findings. Twenty-three patients received chemotherapy. All
      patients were alive at median follow-up of 66 months. Aims of surgery at the
      initiation of treatment were biopsy in 12 cases (1 stereotactic and 11
      craniotomies) and debulking in 7 cases. The 11 open biopsies revealed pilocytic
      astrocytoma; however, noticeable complications occurred in five children after
      the biopsies. Review of preoperative MRIs showed that all had typical findings
      indicating pilocytic astrocytoma. The open biopsy offered no noteworthy benefit
      for the patients despite surgical risk and delay of chemotherapy. The extent of
      the seven resection surgeries was 70% or less removal, and postoperative adjuvant
      therapy was needed for six of the seven patients. The remaining six children who
      did not undergo surgery obtained remission with chemotherapy alone. After relapse
      in nine patients, 15 bulk-reduction surgeries were performed. Surgical resection
      was not curative in any patient. In five patients, mostly older children, cystic
      expansion of tumor was partially resected, resulting in additional remission. In
      conclusion, considering the risk of open surgery and the effectiveness of
      chemotherapy, the role of surgical intervention is restricted to bulk-reduction
      surgery only when it is inevitable, especially at relapse after chemotherapy.

PMID- 18612050
TI  - Third Journal of the American Board of Family Medicine practice-based research
      theme issue.

PMID- 18612051
TI  - Improving performance in prevention.

PMID- 18612052
TI  - Effect of antibiotics on vulvovaginal candidiasis: a MetroNet study.
AB  - PURPOSE: Vulvovaginal candidiasis (VVC) is believed common after systemic
      antibiotic therapy, yet few studies demonstrate this association. In this pilot
      study, we evaluate the effect of short-course oral antibiotic use on VVC.
      METHODS: Nonpregnant women aged 18 to 64 years who required >or=3 days oral
      antibiotics for nongynecological diseases were recruited from a family medicine
      office. Age-matched (+/-5 years) women seen in the same clinic for noninfectious
      problems were recruited as controls. The main outcomes are incidence of
      symptomatic VVC and prevalence of positive vaginal Candida culture 4 to 6 weeks
      after antibiotics. RESULTS: Eighty (44 in antibiotic group) women were recruited;
      14 of 79 (95% CI, 0.11-0.28) had asymptomatic vaginal Candida cultures positive
      at baseline. During follow-up, 10 of 27 (95% CI, 0.22-0.56) women in antibiotic
      group were Candida culture positive. In contrast, 3 of 27 (95% CI, 0.04-0.28)
      women in the control group were Candida culture positive (relative risk, 3.33; P
      = .03). Meanwhile, 6 of 27 (95% CI, 0.11-0.41) women in antibiotic group
      developed symptomatic VVC whereas none (95% CI, 0-0.12) of the women in the
      control group developed vaginal symptoms (relative risk, infinity; P = .02).
      Baseline Candida culture did not predict subsequent symptomatic VVC after
      antibiotics. CONCLUSION: In this pilot study, the use of short courses of oral
      antibiotics seems to increase prevalence of asymptomatic vaginal Candida
      colonization and incidence of symptomatic VVC. Larger cohort studies are needed
      to confirm these findings.

PMID- 18612053
TI  - Cardiovascular risk education and social support (CaRESS): report of a randomized
      controlled trial from the Kentucky Ambulatory Network (KAN).
AB  - PURPOSE: Test a practice-based intervention to foster involvement of a relative
      or friend for the reduction of cardiovascular risk in patients with type 2
      diabetes. METHODS: We enrolled in a randomized controlled trial 199 patients and
      108 support persons (SPs) from 18 practices within a practice-based research
      network. All patient participants had type 2 diabetes with suboptimal blood
      pressure control and were prepared to designate a SP. A subset of the patients
      also had dyslipidemia. All study visits were conducted at the practice sites
      where staff took standardized blood pressure measurements and collected blood
      samples. All patients completed one education session and received newsletters
      aimed at improving key health behaviors. Intervention group patients included
      their chosen SP in the education session and the SPs received newsletters.
      RESULTS: After 9 to 12 months, the intervention had no significant effect on
      systolic blood pressure, HbA1C, health-related quality of life, patient
      satisfaction, medication adherence, or perceived health competence. Power was
      insufficient to detect an effect on low-density lipoprotein cholesterol. Baseline
      cardiovascular risk values were not very high, with mean systolic blood pressure
      at 140 mm Hg; mean HbA1C at 7.6%; and mean low-density lipoprotein at 137 mg/dL.
      Patient health care satisfaction was high. CONCLUSION: This practice-based
      intervention to foster social support for chronic care management among diabetics
      had no significant impact on the targeted outcomes.

PMID- 18612054
TI  - Self determination theory and preventive care delivery: a Research Involving
      Outpatient Settings Network (RIOS Net) study.
AB  - PURPOSE: Traditional approaches to improving preventive care have had limited
      success. In response, researchers have adopted new ways of examining the primary
      care environment and clinical encounters to better understand the factors that
      impact care delivery. We examined how clinicians make preventive counseling
      decisions to ascertain if self-determination theory (SDT) may further clarify
      influences on clinicians' decisions to take time for preventive counseling.
      METHODS: We studied clinical decision making through a mixed-method approach
      using obesity counseling as an example of preventive counseling. We conducted in
      depth interviews and focus groups with 30 primary care clinicians in RIOS Net, a
      Southwestern US practice-based research network and distributed a survey, which
      was completed by 75% of 195 network members. We then used the components of SDT
      autonomy, competence, and relatedness to organize the factors that clinicians
      identified as most influential in their preventive counseling decisions. RESULTS:
      We found that SDT provides an organizing structure for understanding some of the
      psychology of clinicians' decisions to provide preventive counseling in the brief
      primary care encounter. In the specific case of obesity counseling clinicians
      expressed a high degree of autonomy, but barriers to competence and generally low
      levels of relatedness with professional colleagues seemed to limit their delivery
      of preventive counseling. CONCLUSION: SDT provides a new perspective on factors
      that impact preventive counseling delivery, with a focus on the psychology of
      clinical decision making. Further research testing the predictive value of SDT
      may open new avenues for enhancing the delivery of preventive services.

PMID- 18612056
TI  - High blood pressure knowledge among primary care patients with known
      hypertension: a North Carolina Family Medicine Research Network (NC-FM-RN) study.
AB  - BACKGROUND: We sought to assess primary care patients' current knowledge about
      various aspects of high blood pressure (BP). METHODS: We mailed a questionnaire
      to 700 hypertensive patients enrolled in a practice-based research network cohort
      from 24 practices in North Carolina. We determined percentages of respondents
      (total and by subgroups) incorrectly answering each of 6 questions pertaining to
      various aspects of high BP. We then examined bivariate and multivariate
      associations with answering 2 or more items incorrectly ("lower hypertension
      knowledge"). RESULTS: We received 530 completed surveys (76% response rate).
      Twenty-six percent (95% CI, 22-30) of respondents did not know that most of the
      time people with high BP do not feel it. Twenty-two percent (95% CI, 18-26)
      either were not sure whether anything could be done to prevent high BP or believe
      that there is nothing that can be done. Nineteen percent (95% CI, 16-22) either
      believe taking medications will cure high BP or are not sure whether it will.
      Twenty-two percent (95% CI, 19-26) of respondents had overall lower hypertension
      knowledge. Independent associations with lower hypertension knowledge were
      African-American race (odds ratio, 1.77; 95% CI, 1.10-2.86), having less than
      high school education (odds ratio, 2.43; 95% CI, 1.34-4.41), and history of
      stroke/mini-stroke (odds ratio, 1.94; 95% CI, 1.00-3.75). CONCLUSIONS: Patients
      may need to be taught the difference between curing hypertension and treating it
      with medications. Efforts to educate the public that lifestyle modifications can
      prevent hypertension and that it usually causes no symptoms need to continue. It
      seems especially important to develop messages that reach African-Americans and
      people with less education.

PMID- 18612055
TI  - Barriers to supplemental calcium use among women in suburban family practice: a
      report from the Cleveland Clinic Ambulatory Research Network (CleAR-eN).
AB  - BACKGROUND: The majority of adult women in the United States fail to meet daily
      calcium intake recommendations. This study was undertaken to (1) identify
      predictors of calcium supplement use versus non-use, (2) understand barriers to
      calcium supplementation, and (3) determine the potential impact of physician
      recommendation on calcium supplement use. METHODS: Surveys were self-administered
      by 185 women, ages 20 to 64, presenting consecutively for care at 6 suburban
      community-based family medicine practices within the Cleveland Clinic Ambulatory
      Research Network (CleAR-eN). We compared demographic characteristics, health
      beliefs, and health behaviors of those women who reported never using calcium
      supplements with those who presently took calcium supplements. Women who never
      took calcium were also queried about reasons for non-use and whether physician
      recommendation would influence their adoption of calcium supplementation.
      RESULTS: Multivitamin use, self-perceived risk of osteoporosis, and age were
      independent predictors of calcium supplement use. Leading barriers for never
      users were lack of knowledge about the need/importance of increasing calcium
      intake, lack of motivation to start supplements, and the belief that their
      dietary calcium intake alone was sufficient. Ninety-six percent of never-users
      reported that they would consider taking a calcium supplement if recommended by
      their physician. CONCLUSIONS: Many patient-identified barriers to calcium
      supplementation seem amenable to focused and brief office-based interventions
      that could increase the number of women meeting calcium intake guidelines.

PMID- 18612057
TI  - Underinsurance in primary care: a report from the State Networks of Colorado
      Ambulatory Practices and Partners (SNOCAP).
AB  - BACKGROUND: There has been considerable focus on the uninsured from national and
      state levels. There are also many Americans who have health insurance but are
      unable to afford their recommended care and are considered underinsured. This
      purpose of this study was to determine the prevalence of underinsurance among
      patients seen in primary care clinics. METHODS: Patients in 37 primary care
      practices in 3 practice-based research networks completed a survey to elicit the
      prevalence of underinsurance among those who had insurance for a full 12 months,
      including private insurance, Medicare, and Medicaid. Being underinsured was based
      on patients reporting the delay or omission of recommended care because of their
      inability to afford it. RESULTS: Of those with insurance for a full year, 36.3%
      were underinsured. Of those who were underinsured, 50.2% felt that their health
      suffered because they could not afford recommended care, a rate similar among
      those who were uninsured. CONCLUSIONS: When evaluating underinsurance in primary
      care offices, using an experiential definition based on self-reports of patients
      about their inability to pay for recommended health care despite having
      insurance, the prevalence is quite high. It is important for the primary care
      physician to understand that a substantial percentage of their patients may not
      follow through with their recommendations because of cost, despite having
      insurance. This also has significant implications when considering health care
      reform, particularly considering that these patients reported that their health
      suffered at a rate equal to that of the uninsured.

PMID- 18612058
TI  - Efficiency of a two-item pre-screen to reduce the burden of depression screening
      in pregnancy and postpartum: an IMPLICIT network study.
AB  - OBJECTIVE: Systems for efficient case finding of women with major depression
      during pregnancy and postpartum are needed. Here we assess the diagnostic
      accuracy of a modified 2-item patient health questionnaire (PHQ-2) as a pre
      screen in assessing depression. METHODS: Cross-sectional assessments at 15 weeks'
      gestation (n = 414), 30 weeks' gestation (n = 334), and 6 to 16 weeks postpartum
      (n = 193) among women from a diverse set of races/ethnicities, participating in
      the IMPLICIT maternal care quality improvement network. The Edinburgh Postnatal
      Depression Scale score (>or=13) was used as the criterion measure for the PHQ-2.
      RESULTS: A positive 2-item screen had sensitivity of 93%, 82%, and 80% and
      specificity of 75%, 80%, and 86% for Edinburgh Postnatal Depression Scale score
      of >or=13 for assessment at 15 and 30 weeks gestational age and postpartum,
      respectively. The positive/negative predictive values for the PHQ-2 were 44/98,
      24/91, and 30/98 for each time point, respectively. Areas under the receiver
      operating characteristic curve analysis suggested that 2-item assessments at each
      time point had approximately equal diagnostic validity. CONCLUSIONS: Two
      questions were efficient to rule out depression and reduced the need for further
      screening of approximately 60% to 80% of women, depending on the point in
      pregnancy or postpartum. A diagnostic interview follow-up of women screening
      positive is still required.

PMID- 18612059
TI  - Improving mammography screening using best practices and practice enhancement
      assistants: an Oklahoma Physicians Resource/Research Network (OKPRN) study.
AB  - PURPOSE: In 2004 only 68% of women in Oklahoma over the age of 40 reported having
      a mammogram in the past 2 years, compared with 75% nationally. Strategies to
      improve mammography rates have been numerous but have generally included single
      strategies, such as physician education, practice audit and feedback, and
      reminders; flow sheets and results have been mixed. The purpose of this
      randomized controlled trial was to determine the impact of a practice facilitator
      and "best practice" interventions on mammography rates in a practice-based
      research network. METHODS: A total of 16 practices participated; 8 were assigned
      to intervention and 8 to usual care. Pre- and post-audits of mammography rates
      were conducted. Intervention practices received feedback with benchmarking,
      academic detailing, and the assistance of a practice enhancement assistant to
      help with practice redesign over a 9-month period. RESULTS: The groups differed
      significantly for both the proportion of mammograms offered to eligible patients
      (P = .043) and for the proportion of patients with current mammograms (P < .015).
      For the control group, 38% of eligible women were offered a mammogram and 202
      (35% of those eligible) actually did have documentation that a mammogram had been
      performed. Fifty-three percent of the eligible patients in the intervention group
      were offered a mammogram and 52% of those eligible (n = 332) did have
      documentation in the chart that the mammogram had been completed. CONCLUSION: The
      results suggest that these interventions can improve mammography rates in a range
      of practice settings. These findings are consistent with other studies that have
      tested multicomponent interventions.

PMID- 18612060
TI  - Implementation of evidence-based preventive services delivery processes in
      primary care: an Oklahoma Physicians Resource/Research Network (OKPRN) study.
AB  - BACKGROUND: Previous research has found that wellness visits, recall and reminder
      systems, and standing orders are associated with higher rates of delivery of
      preventive services in primary care practices. However, there is little
      information about how to help practices implement these processes. METHODS: A 6
      month randomized, controlled trial comparing a multicomponent quality improvement
      intervention to feedback and benchmarking. One clinician/nurse team from each of
      24 practices was randomly assigned to one of 2 study arms. Intervention practices
      received performance feedback, peer-to-peer education (academic detailing), a
      practice facilitator, and computer (information technology) support.
      Implementation of the 3 targeted processes was determined by a blinded 3
      clinician panel that reviewed transcribed clinician interviews before and after
      intervention using performance definitions. Rates of delivery of selected
      preventive services were determined by chart audit. RESULTS: Intervention
      practices implemented more of the processes than control practices overall (P =
      .003), for adults (P = .05), and for children (P = .04). They were also more
      likely to implement at least one of the processes for children (P = .04) and to
      implement standing orders for either children or adults (P = .02). Mammography
      rates increased significantly. Neither clinician and practice characteristics nor
      clinician readiness to change predicted implementation. CONCLUSIONS: A
      multicomponent implementation strategy consisting of feedback, benchmarking,
      academic detailing, facilitation, and IT support increased implementation of
      evidence-based processes for delivering preventive services to a greater extent
      than performance feedback and benchmarking alone.

PMID- 18612061
TI  - Institutional review board training for community practices: advice from the
      Agency for Health Care Research and Quality Practice-Based Research Network
      listserv.
AB  - Human subject protection training is required for all research personnel
      regardless of funding source. This article summarizes recommendations from a
      discussion about ethics training for community personnel from the practice-based
      research network (PBRN) listserv sponsored by the Agency for Health Care Research
      and Quality PBRN Resource Center. PBRN projects can involve community providers
      and their staff as subjects of the research project or as collaborators with
      recruitment and data collection. Distinguishing between usual care and research
      procedures is important for determining if training is required of community
      based personnel. The use of research assistants or practice facilitators to
      collect research-related information is one way of limiting practice involvement
      to usual care procedures, thereby allowing PBRNs to limit training to dedicated
      research staff. Key methodologies for human subject protection training of
      community practice staff include on-site lectures, online modules, videotapes,
      and paper-based training. Ultimately, a discussion by the PBRN researcher with
      his or her governing Institutional Review Board is recommended for finding
      acceptable strategies within a PBRN.

PMID- 18612062
TI  - Practice-based research network membership is associated with retention of
      clinicians in underserved communities: a Research Involving Outpatient Settings
      Network (RIOS Net) study.
AB  - BACKGROUND: Professional isolation is a barrier to practicing in rural and
      underserved communities. The purpose of this study was to investigate the
      association between membership in a practice-based research network and the
      length of employment in members' and nonmembers' current clinic sites. METHODS:
      This was a cross sectional study of 7 group practices (2 urban and 5 rural groups
      comprising 22 clinic sites) throughout New Mexico that had RIOS Net member and
      nonmember practicing clinicians. RESULTS: The 22 clinics employed 95 clinicians,
      of which 43% were RIOS Net members (21 of 59 MDs, 8 of 18 Nurse Practitioners, 9
      of 15 Physician Assistants and 3 of 3 others). RIOS Net members had a
      significantly longer mean employment time (7.0 years; SD, 6.8 years; median, 5.0
      years), compared with non-RIOS Net members (4.0 years; SD, 5.0 years; median, 2.3
      years; P = .003). Similar results were found when analyzed by length of time in
      practice with cutoffs of 2 and 5 years. DISCUSSION: Being a member of a practice
      based research network may be a determinate of staying in rural practice longer.
      This is a hypothesis-generating study and needs confirmation from larger studies
      whose analysis stratifies clinician demographics and practice type.

PMID- 18612063
TI  - A novel approach using an electronic medical record to identify children and
      adolescents at risk for dyslipidemia: a study from the Primary Care Education and
      Research Learning (PEARL) network.
AB  - PURPOSE: We conducted a retrospective analysis to identify children and
      adolescents in the Primary Care Education and Research Learning practice-based
      research network (PBRN) who were at risk for dyslipidemia. METHODS: Using coding
      data from an electronic medical record to identify all adults with an underlying
      diagnosis of hyperlipidemia enrolled to this PBRN, children at risk for
      dyslipidemia were identified. RESULTS: Enrolled to this network were 189,282
      patients, including 55,252 children aged 2 to 18 years. The prevalence of
      physician-coded hyperlipidemia in the adult population was 1.5%. Two percent of
      the children enrolled to this PBRN were at risk for dyslipidemia. CONCLUSION:
      Using technology within electronic medical records allowed for the identification
      of children at risk for dyslipidemia and to create clinical reminders that will
      allow us to improve the efficiency of screening efforts.

PMID- 18612064
TI  - Adoption of exercise and readiness to change differ between Whites and African
      Americans with hypertension: a report from the Ohio State University Primary Care
      Practice-Based Research Network (OSU-PCPBRN).
AB  - BACKGROUND: Hypertension is a major cause of morbidity and mortality in the
      United States and disproportionately affects African-Americans. A cornerstone to
      treatment is nonpharmacologic lifestyle modifications. Despite such
      recommendations, many patients fail to exercise. METHODS: An anonymous survey (n
      = 285) of hypertensive patients cared for at 2 offices within the Ohio State
      University Primary Care Practice-Based Research Network. Survey questions
      included demographics, recommendations for diet, and exercise lifestyle
      modification for reducing blood pressure. Questions were phrased as multiple
      choice or based on Prochaska and DiClemente's readiness to change model. RESULTS:
      Of the 244 respondents, 57% were women and 43% were African-American. The income
      of African-Americans was significantly lower than that of whites. Exercise and
      increased fruit/vegetable consumption were the preferred lifestyle modifications
      and did not differ by race. Race and exercise were associated; a majority of
      whites were engaged in exercise whereas this was not so for African Americans.
      CONCLUSIONS: Although exercise as a preferred lifestyle modification habit does
      not differ by race, implementation of such a behavior does. This may be related
      to differing income levels. When counseling patients, physicians must be prepared
      to ask what may hinder the adoption of such behavior and be prepared to offer
      possible solutions to overcoming such factors.

PMID- 18612065
TI  - Primary care of overweight children: the importance of parent weight and
      attitudes about overweight: a MetroNet study.
AB  - PURPOSE: The purpose of this study was to identify the association of parents'
      weight and attitude about their child's weight with the child's body mass index
      (BMI) status. DESIGN: Cross-sectional, clinic-based study in a practice-based
      research network. METHODS: One hundred seventy-one parents or adults accompanying
      children aged 5 to 17 years to a primary care visit in 4 family medicine centers
      completed a questionnaire. Parent/adult overweight status and attitudes were
      compared with child overweight status. RESULTS: Forty-eight percent of children
      were overweight or obese (BMI >or= the 85th percentile) as were 56% of mothers
      and 77% of fathers (BMI >or= 25 kg/m(2)). Child and parent overweight were
      significantly associated, as were mother overweight and beliefs about child
      overweight status. Children aged 5 to 13 years were more likely to be overweight
      than those aged >or=14 years. CONCLUSIONS: Parents of overweight children are
      often overweight and many do not recognize that their children are overweight.
      Suggestions are made for primary care physicians to engage parents of overweight
      children in family weight control efforts.

PMID- 18612066
TI  - Family medicine: a complete relationship.

PMID- 18612068
TI  - The touchscreen cognitive testing method for rodents: how to get the best out of
      your rat.
AB  - The touchscreen testing method for rodents is a computer-automated behavioral
      testing method that allows computer graphic stimuli to be presented to rodents
      and the rodents to respond to the computer screen via a nose-poke directly to the
      stimulus. The advantages of this method are numerous; however, a systematic study
      of the parameters that affect learning has not yet been conducted. We therefore
      sought to optimize stimuli and task parameters in this method. We found that when
      parameters were optimized, Lister Hooded rats could learn rapidly using this
      method, solving a discrimination of two-dimensional stimuli to a level of 80%
      within five to six sessions lasting approximately 30 min each. In a final
      experiment we tested both male and female rats of the albino Sprague-Dawley
      strain, which are often assumed to have visual abilities far too poor to be
      useful for studies of visual cognition. The performance of female Sprague-Dawley
      rats was indistinguishable from that of their male counterparts. Furthermore,
      performance of male Sprague-Dawley rats was indistinguishable from that of their
      Lister Hooded counterparts. Finally, Experiment 5 examined the ability of Lister
      Hooded rats to learn a discrimination between photographic stimuli. Under
      conditions in which parameters were optimized, rats were remarkably adept at this
      discrimination. Taken together, these experiments served to optimize the
      touchscreen method and have demonstrated its usefulness as a high-throughput
      method for the cognitive testing of rodents.

PMID- 18612067
TI  - Glucocorticoids enhance taste aversion memory via actions in the insular cortex
      and basolateral amygdala.
AB  - It is well established that glucocorticoid hormones strengthen the consolidation
      of hippocampus-dependent spatial and contextual memory. The present experiments
      investigated glucocorticoid effects on the long-term formation of conditioned
      taste aversion (CTA), an associative learning task that does not depend
      critically on hippocampal function. Corticosterone (1.0 or 3.0 mg/kg)
      administered subcutaneously to male Sprague-Dawley rats immediately after the
      pairing of saccharin consumption with the visceral malaise-inducing agent lithium
      chloride (LiCl) dose-dependently increased aversion to the saccharin taste on a
      96-h retention test trial. In a second experiment, rats received corticosterone
      either immediately after saccharin consumption or after the LiCl injection, when
      both stimuli were separated by a 3-h time interval, to investigate whether
      corticosterone enhances memory of the gustatory or visceral stimulus
      presentation. Consistent with the finding that the LiCl injection, but not
      saccharin consumption, increases endogenous corticosterone levels, corticosterone
      selectively enhanced CTA memory when administered after the LiCl injection.
      Suppression of this training-induced release of corticosterone with the synthesis
      inhibitor metyrapone (35 mg/kg) impaired CTA memory, and was dose-dependently
      reversed by post-training supplementation of corticosterone. Moreover, direct
      post-training infusions of corticosterone into the insular cortex or basolateral
      complex of the amygdala, two brain regions that are critically involved in the
      acquisition and consolidation of CTA, also enhanced CTA retention, whereas post
      training infusions into the dorsal hippocampus were ineffective. These findings
      provide evidence that glucocorticoid effects on memory consolidation are not
      limited to hippocampus-dependent spatial/contextual information, but that these
      hormones also modulate memory consolidation of discrete-cue associative learning
      via actions in other brain regions.

PMID- 18612069
TI  - Theta synchronizes the activity of medial prefrontal neurons during learning.
AB  - Memory consolidation is thought to involve the gradual transfer of transient
      hippocampal-dependent traces to distributed neocortical sites via the rhinal
      cortices. Recently, medial prefrontal (mPFC) neurons were shown to facilitate
      this process when their activity becomes synchronized. However, the mechanisms
      underlying this enhanced synchrony remain unclear. Because the hippocampus
      projects to the mPFC, we tested whether theta oscillations contribute to
      synchronize mPFC neurons during learning. Thus, we obtained field (LFP) and unit
      recordings from multiple mPFC sites during the acquisition of a trace
      conditioning task, where a visual conditioned stimulus (CS) predicted reward
      delivery. In quiet waking, the activity of mPFC neurons was modulated by theta
      oscillations. During conditioning, CS presentation caused an increase in mPFC
      theta power that augmented as the CS gained predictive value for reward delivery.
      This increased theta power coincided with a transient theta phase locking at
      distributed mPFC sites, an effect that was also manifest in the timing of mPFC
      unit activity. Overall, these results show that theta oscillations contribute to
      synchronize neuronal activity at distributed mPFC sites, suggesting that the
      hippocampus, by generating a stronger theta source during learning, can
      synchronize mPFC activity, in turn facilitating rhinal transfer of its activity
      to the neocortex.

PMID- 18612070
TI  - Is the loss of stability theory a realistic concept for stress relaxation
      mediated cell wall expansion during plant growth?

PMID- 18612071
TI  - Nutritionally improved agricultural crops.

PMID- 18612072
TI  - Improving the content of essential amino acids in crop plants: goals and
      opportunities.

PMID- 18612073
TI  - Enhancing plant seed oils for human nutrition.

PMID- 18612074
TI  - Molecular plant breeding as the foundation for 21st century crop improvement.

PMID- 18612076
TI  - Targeting ceramide metabolism with a potent and specific ceramide kinase
      inhibitor.
AB  - Ceramide kinase (CerK) produces the bioactive lipid ceramide-1-phosphate (C1P)
      and appears as a key enzyme for controlling ceramide levels. In this study, we
      discovered and characterized adamantane-1-carboxylic acid (2-benzoylamino
      benzothiazol-6-yl)amide (NVP-231), a potent, specific, and reversible CerK
      inhibitor that competitively inhibits binding of ceramide to CerK. NVP-231 is
      active in the low nanomolar range on purified as well as cellular CerK and
      abrogates phosphorylation of ceramide, resulting in decreased endogenous C1P
      levels. When combined with another ceramide metabolizing inhibitor, such as
      tamoxifen, NVP-231 synergistically increased ceramide levels and reduced cell
      growth. Therefore, NVP-231 represents a novel and promising compound for
      controlling ceramide metabolism that may provide insight into CerK physiological
      function.

PMID- 18612075
TI  - Unraveling the tapestry of networks involving reactive oxygen species in plants.

PMID- 18612079
TI  - Human proximal tubular epithelium actively secretes but does not retain
      rosuvastatin.
AB  - Rosuvastatin is a potent HMG-CoA reductase inhibitor that has proven to be
      effective in the treatment of dyslipidemia. Rosuvastatin is cleared from the body
      by both biliary and renal clearance, the latter believed to be due to active
      tubular secretion. Whereas the mechanisms of hepatic clearance of rosuvastatin
      are well documented, those of renal clearance are not. Because rosuvastatin (and
      other statins) may alter proximal tubular function, this study aimed to
      characterize the mechanisms of tubular rosuvastatin secretion to define the
      factors that could influence the presence/concentration of rosuvastatin in
      proximal tubular cells. Hereto, polarized monolayers of primary human tubular
      cells were used. We found rosuvastatin net secretion across proximal tubule
      cells, which was saturable (K50=20.4+/-4.1 microM). The basolateral uptake step
      was rate-limiting and mediated by OAT3. Rosuvastatin efflux at the apical
      membrane was mediated by MRP2/4 and ABCG2 together with a small contribution from
      MDR1 or P-glycoprotein. These data, obtained in an intact human tubule cell
      model, provide a detailed insight into rosuvastatin's renal handling and the
      possible factors influencing it.

PMID- 18612078
TI  - Dysregulation of purine nucleotide biosynthesis pathways modulates cisplatin
      cytotoxicity in Saccharomyces cerevisiae.
AB  - We found previously that inactivation of the FCY2 gene, encoding a purine
      cytosine permease, or the HPT1 gene, encoding the hypoxanthine guanine
      phosphoribosyl transferase, enhances cisplatin resistance in yeast cells. Here,
      we report that in addition to fcy2Delta and hpt1Delta mutants in the salvage
      pathway of purine nucleotide biosynthesis, mutants in the de novo pathway that
      disable the feedback inhibition of AMP and GMP biosynthesis also enhanced
      cisplatin resistance. An activity-enhancing mutant of the ADE4 gene, which
      constitutively synthesizes AMP and excretes hypoxanthine, and a GMP kinase mutant
      (guk1), which accumulates GMP and feedback inhibits Hpt1 function, both enhanced
      resistance to cisplatin. In addition, overexpression of the ADE4 gene in wild
      type cells, which increases de novo synthesis of purine nucleotides, also
      resulted in elevated cisplatin resistance. Cisplatin cytotoxicity in wild-type
      cells was abolished by low concentration of extracellular purines (adenine,
      hypoxanthine, and guanine) but not cytosine. Inhibition of cytotoxicity by
      exogenous adenine was accompanied by a reduction of DNA-bound cisplatin in wild
      type cells. As a membrane permease, Fcy2 may mediate limited cisplatin transport
      because cisplatin accumulation in whole cells was slightly affected in the
      fcy2Delta mutant. However, the fcy2Delta mutant had a greater effect on the
      amount of DNA-bound cisplatin, which decreased to 50 to 60% of that in the wild
      type cells. Taken together, our results indicate that dysregulation of the purine
      nucleotide biosynthesis pathways and the addition of exogenous purines can
      modulate cisplatin cytotoxicity in Saccharomyces cerevisiae.

PMID- 18612077
TI  - Differential activation and trafficking of micro-opioid receptors in brain
      slices.
AB  - The activation of G protein-coupled receptors results in a cascade of events that
      include acute signaling, desensitization, and internalization, and it is thought
      that not all agonists affect each process to the same extent. The early steps in
      opioid receptor signaling, including desensitization, have been characterized
      electrophysiologically using brain slice preparations, whereas most previous
      studies of opioid receptor trafficking have been conducted in heterologous cell
      models. This study used transgenic mice that express an epitope-tagged (FLAG)
      micro-opioid receptor (FLAGMOR) targeted to catecholamine neurons by regulatory
      elements from the tyrosine hydroxylase gene. Brain slices from these mice were
      used to study tagged MOR receptors in neurons of the locus ceruleus. Activation
      of the FLAGMOR with [Met5]enkephalin (ME) produced a hyperpolarization that
      desensitized acutely to the same extent as native MOR in slices from wild-type
      mice. A series of opioid agonists were then used to study desensitization and
      receptor trafficking in brain slices, which was monitored with a monoclonal
      antibody against the FLAG epitope (M1) conjugated to Alexa 594. Three patterns of
      receptor trafficking and desensitization were observed: 1) ME, etorphine, and
      methadone resulted in both receptor desensitization and internalization; 2)
      morphine and oxymorphone caused significant desensitization without evidence for
      internalization; and 3) oxycodone was ineffective in both processes. These
      results show that two distinct forms of signaling were differentially engaged
      depending on the agonist used to activate the receptor, and they support the
      hypothesis that ligand-specific regulation of opioid receptors occurs in neurons
      maintained in brain slices from adult animals.

PMID- 18612080
TI  - Functional role of arginine 375 in transmembrane helix 6 of multidrug resistance
      protein 4 (MRP4/ABCC4).
AB  - Multidrug resistance protein (MRP) 4 transports a variety of endogenous and
      xenobiotic organic anions. MRP4 is widely expressed in the body and specifically
      localized to the renal apical proximal tubule cell membrane, where it mediates
      the excretion of these compounds into urine. To characterize the MRP4 substrate
      binding site, the amino acids Phe368, Phe369, Glu374, Arg375, and Glu378 of
      transmembrane helix 6, and Arg998 of helix 12, localized in the intracellular
      half of the central pore, were mutated into the corresponding amino acids of MRP1
      and MRP2. Membrane vesicles isolated from human embryonic kidney 293 cells
      overexpressing these mutants showed significantly reduced methotrexate (MTX) and
      cGMP transport activity compared with vesicles that expressed wild-type MRP4. The
      only exception was substitution of Arg375 with serine, which had no effect on
      cGMP transport but significantly decreased the affinity of MTX. Substitution of
      the same amino acid with a positively charged lysine returned the MTX affinity to
      that of the wild type. Furthermore, MTX inhibition of MRP4-mediated cGMP
      transport was noncompetitive, and the inhibition constant was increased by
      introduction of the R375S mutation. A homology model of MRP4 showed that Arg375
      and Arg998 face right into the central aqueous pore of MRP4. We conclude that
      positively charged amino acids in transmembrane helices 6 and 12 contribute to
      the MRP4 substrate-binding pocket.

PMID- 18612081
TI  - Germ line activation of the Tie2 and SMMHC promoters causes noncell-specific
      deletion of floxed alleles.
AB  - Tissue-specific knockouts generated through Cre-loxP recombination have become an
      important tool to manipulate the mouse genome. Normally, two successive rounds of
      breeding are performed to generate mice carrying two floxed target-gene alleles
      and a transgene expressing Cre-recombinase tissue-specifically. We show herein
      that two promoters commonly used to generate endothelium-specific (Tie2) and
      smooth muscle-specific [smooth muscle myosin heavy chain (Smmhc)] knockout mice
      exhibit activity in the female and male germ lines, respectively. This can result
      in the inheritance of a null allele in the second generation that is not tissue
      specific. Careful experimental design is required therefore to ensure that tissue
      specific knockouts are indeed tissue specific and that appropriate controls are
      used to compare strains.

PMID- 18612082
TI  - Prioritization of candidate disease genes for metabolic syndrome by computational
      analysis of its defining phenotypes.
AB  - There is a rapid increase in the world-wide burden of disease attributed to
      metabolic syndrome, as defined by co-occurrence of an array of phenotypes
      including abdominal obesity, dysglycemia, hypertriglyceridemia, low levels of
      high density lipoprotein cholesterol, and hypertension. Familial studies clearly
      indicate a genetic component to the disease and many linkage studies have
      identified a large number of linked loci. No disease-causing genes, however, have
      been conclusively identified, most likely because this is a multigenic disease
      for which effects of many causative genes may be small and combined with
      environmental effects. To assist empirical identification of metabolic syndrome
      associated genes, we present here a novel computational approach to prioritize
      candidate genes. We have used linkage studies and the clinical and population
      specific presentation of the disease to select a final candidate gene list of 19
      most likely disease-causing genes. These are predominantly involved in
      chylomicron processing, transmembrane receptor activity, and signal transduction
      pathways. We propose here that information about the clinical presentation of a
      complex trait can be used to effectively inform computational prioritization of
      disease-causing genes for that trait.

PMID- 18612083
TI  - Identification of a major locus for islet inflammation and fibrosis in the
      spontaneously diabetic Torii rat.
AB  - The pathogenesis of inflammation and fibrosis in the pancreatic islets in
      diabetes is largely unknown. Spontaneously diabetic Torii (SDT) rats exhibit
      inflammation and fibrosis in and around the islets during the development of the
      disease. We investigated genetic factors for diabetes, islet inflammation, and
      fibrosis in the SDT rat. We produced F1 and F2 rats by intercross between SDT and
      F344 rats, examined the onset of diabetes, glucose tolerance, and histology of
      the pancreas, and performed genetic analysis of these traits. We then established
      a congenic strain carrying the SDT allele at the strongest diabetogenic locus on
      the F344 genetic background and characterized glucose tolerance and histology of
      the pancreas. F1 rats showed glucose intolerance and inflammatory changes mainly
      in the islets. Genetic analysis of diabetes identified a major locus on
      chromosome 3, designated Dmsdt1, at which a dominantly acting SDT allele was
      involved. Quantitative trait locus (QTL) analysis of glucose tolerance revealed,
      in addition to Dmsdt1 [logarithm of odds (LOD) 5.3 near D3Mit12], three other
      loci, designated Dmsdt2 (LOD 4.2 at D8Rat46), Dmsdt3 (LOD 3.8 near D13Arb5), and
      Dmsdt4 (LOD 5.8 at D14Arb18). Analysis of a congenic strain for Dmsdt1 indicates
      that the dominantly acting SDT allele induces islet inflammation and fibrosis.
      Thus we have found a major locus on chromosome 3 for islet inflammation and
      fibrosis in the SDT rat. Identification of the genes responsible should provide
      insight into the pathogenesis of diabetes.

PMID- 18612084
TI  - Shared gene expression profiles in developing heart valves and osteoblast
      progenitor cells.
AB  - The atrioventricular (AV) valves of the heart develop from undifferentiated
      mesenchymal endocardial cushions, which later mature into stratified valves with
      diversified extracellular matrix (ECM). Because the mature valves express genes
      associated with osteogenesis and exhibit disease-associated calcification, we
      hypothesized the existence of shared regulatory pathways active in developing AV
      valves and in bone progenitor cells. To define gene regulatory programs of
      valvulogenesis relative to osteoblast progenitors, we undertook Affymetrix gene
      expression profiling analysis of murine embryonic day (E)12.5 AV endocardial
      cushions compared with E17.5 AV valves (mitral and tricuspid) and with
      preosteoblast MC3T3-E1 (subclone4) cells. Overall, MC3T3 cells were significantly
      more similar to E17.5 valves than to E12.5 cushions, supporting the hypothesis
      that valve maturation involves the expression of many genes also expressed in
      osteoblasts. Several transcription factors characteristic of mesenchymal and
      osteoblast precursor cells, including Twist1, are predominant in E12.5 cushion.
      Valve maturation is characterized by differential regulation of matrix
      metalloproteinases and their inhibitors as well as complex collagen gene
      expression. Among the most highly enriched genes during valvulogenesis were
      members of the small leucine-rich proteoglycan (SLRP) family including Asporin, a
      known negative regulator of osteoblast differentiation and mineralization.
      Together, these data support shared gene expression profiles of the developing
      valves and osteoblast bone precursor cells in normal valve development and
      homeostasis with potential functions in calcific valve disease.

PMID- 18612085
TI  - Astrocyte responses after neonatal ischemia: the yin and the yang.
AB  - Neonatal encephalopathy is a major predictor of neurodevelopmental disability in
      term infants and occurs in 1 to 6 of every 1,000 live term births. Despite
      improvements in perinatal practice during the past several decades, the incidence
      of cerebral palsy attributed to neonatal asphyxia remained essentially unchanged,
      primarily because management strategies were supportive and not targeted toward
      the processes of ongoing injury. Traditionally, experimental research in vivo
      focused on neurons, and more recently, oligodendrocytes whereas astrocytes have
      been more or less neglected. This review aims at dissecting possible protective
      as well as destructive roles of astrocytes in the immature ischemic brain to
      stimulate further research into this unexplored aspect of brain pathophysiology.

PMID- 18612086
TI  - Synaptic plasticity from visual cortex to hippocampus: systems integration in
      spatial information processing.
AB  - The adult cerebral cortex possesses the remarkable ability to change its neuronal
      connectivity through experience, a phenomenon termed "synaptic plasticity."
      Synaptic plasticity constitutes a cellular mechanism that is thought to underlie
      information storage and memory formation in the brain, and represents a use
      dependent long-lasting increase or decrease in synaptic strength. Recent
      findings, that the adult visual cortex undergoes dynamic synaptic plasticity that
      is driven by active visual experience, suggest that it may be involved in
      information processing that could contribute to memory formation. The visual
      cortex provides a crucial sensory input to the hippocampus, and is a key
      component for the creation of spatial memories. An understanding of how visual
      cortical neurons respond with synaptic plasticity to visual experience, and
      whether these responses influence the induction of hippocampal plasticity, is
      fundamental to our understanding of the neuronal mechanisms and functional
      consequences of visuospatial information processing. In this review, we summarize
      recent findings with regard to the expression of dynamic synaptic plasticity in
      the visual cortex and how this plasticity may influence information processing in
      the hippocampus.

PMID- 18612087
TI  - Cognitive role of neurogenesis in depression and antidepressant treatment.
AB  - The discovery of newborn neurons in the adult brain has generated enormous
      interest over the past decade. Although this process is well documented in the
      hippocampus and olfactory bulb, the possibility of neuron formation in other
      brain regions is under vigorous debate. Neurogenesis within the adult hippocampus
      is suppressed by factors that predispose to major depression and stimulated by
      antidepressant interventions. This pattern has generated the hypothesis that
      impaired neurogenesis is pathoetiological in depression and stimulation of
      newborn neurons essential for effective antidepressant action. This review
      critically evaluates the evidence in support of and in conflict with this theory.
      The literature is divided into three areas: neuronal maturation, factors that
      influence neurogenesis rates, and function of newborn neurons. Unique elements in
      each of these areas allow for the refinement of the hypothesis. Newborn
      hippocampal neurons appear to be necessary for detecting subtle environmental
      changes and coupling emotions to external context. Thus speculatively, stress
      induced suppression of neurogenesis would uncouple emotions from external context
      leading to a negative mood state. Persistence of negative mood beyond the
      duration of the initial stressor can be defined as major depression.
      Antidepressant-induced neurogenesis therefore would restore coupling of mood with
      environment, leading to the resolution of depression. This conceptual framework
      is provisional and merits evaluation in further experimentation. Critically,
      manipulation of newborn hippocampal neurons may offer a portal of entry for more
      effective antidepressant treatment strategies.

PMID- 18612088
TI  - Predictors of work engagement among medical-surgical registered nurses.
AB  - This descriptive, cross-sectional study examines the relationship of job
      satisfaction, turnover cognitions, job search behavior, and nurse demographics to
      work engagement among a sample of 167 registered nurses employed on medical
      and/or surgical units within six hospitals. Professional status, interaction, and
      thinking of quitting together explain 46%, F(3,160) = 47.546, p < .001, of the
      variance in work engagement. Additionally, the job satisfaction components of
      professional status and interaction are shown to significantly moderate the
      relationship between thinking of quitting and work engagement (t = 1.96, p <
      .05). Results suggest improvements in work environment processes that are
      consistent with professional status and interaction at work, such as integration
      of a professional nursing practice model and development and positioning of
      transformational leaders at every level of the organization, are needed.

PMID- 18612089
TI  - Predictors of job satisfaction for rural acute care registered nurses in Canada.
AB  - This study examines predictors of job satisfaction among rural acute care
      registered nurses. The data are from a cross-sectional national survey, which was
      part of a larger project, The Nature of Nursing Practice in Rural and Remote
      Canada. This analysis suggests that a combination of individual, workplace, and
      community characteristics are interrelated predictors of job satisfaction for
      rural acute care nurses. There were nine variables that accounted for 38% of the
      total variance in job satisfaction. Four variables alone (available and up-to
      date equipment and supplies, satisfaction with scheduling and shifts, lower
      psychological job demands, and home community satisfaction) explained 33% of the
      variance. Recruitment and retention strategies in rural areas must acknowledge
      that rural nurses' work lives and community lives are inextricably intertwined.
      Attention to these issues will help ensure high-quality working environments and
      a continued commitment to quality nursing care in the rural hospital settings in
      Canada.

PMID- 18612090
TI  - Qigong improving physical status in middle-aged women.
AB  - Regular exercise has been shown to benefit its practitioners and prevent and
      control diseases. Muscle/Tendon Change Classic (MTCC) qigong, characterized by
      simple, slow, and full-body exercise, is appropriate for the middle-age
      population. This study aims to evaluate the effect of the MTCC qigong program in
      improving physical status for middle-aged women. A quasi-experimental design was
      used. The experimental group (n = 37) received an 8-week MTCC qigong program,
      whereas the control group (n = 34) received none. Physiological parameters of
      muscular performance, body composition, and bone strength were measured before
      and after the program. The average age was 49 +/- 4.13 years for the experimental
      group and 50 +/- 4.74 years for the control group. The demographic
      characteristics were homogeneous between the two groups. There were statistically
      significant differences between the two groups in muscular endurance, body fat,
      waist-to-hip ratio, and body mass index at the completion of 8-week MTCC qigong
      program. The MTCC qigong could improve muscle endurance and body composition but
      not bone strength for middle-aged women, thereby demonstrating the qigong
      practice has certain health-preserving effects on women in this stage of life.

PMID- 18612091
TI  - Postoperative pain management outcome in Chinese inpatients.
AB  - In the absence of pain management outcome reports representing mainland China,
      the purposes of this study were to describe the outcome of postoperative pain
      management and the relationship between patient satisfaction and clinical
      outcomes in an indigenous Chinese population. From a sample of 388 second-day
      postoperative inpatients, 304 (78%) reported pain in the past 24 hours and were
      enrolled in the study. Mean ratings for pain were moderate to severe. Patients
      reported mild to moderate pain-related interference with mood and physical
      activities. There were significant differences on worst pain intensity and pain
      interference with daily activity in the past 24 hours for different types of
      surgery. Top-ranked nonpharmacologic methods for managing pain were tolerating
      pain, changing positions, and family support. As measured by the Pain Management
      Index, 60.2% of patients were inadequately treated for pain, yet patients
      reported high satisfaction with pain management. Patient satisfaction, however,
      was inversely and significantly correlated with pain intensity. Study results
      indicate a need for standardized policies and guidelines about pain management
      and education among providers and for patients and families to overcome the
      suboptimal pain outcomes among this Chinese population.

PMID- 18612092
TI  - Factors associated with caregiver burden in heart failure family caregivers.
AB  - Fifty caregivers and 41 heart failure patients participated in a study examining
      the association of caregiver characteristics and the caregiving environment on
      caregiver burden. Using a cross-sectional design, caregivers were interviewed
      face-to-face using a caregiver characteristic/demographic tool designed for this
      study, the Centers for Epidemiological Studies Short Depression Scale, the
      Caregiver Reaction Assessment questionnaire, and the New York Heart Association
      Functional Classification Guide to obtain the caregiver's perception of patient
      disease severity. Patient medical records were assessed following caregiver
      interviews for patient demographics, comorbidities, and ejection fraction
      percentages. Significantly higher levels of burden were found among Caucasian
      caregivers, those caring for other relatives besides the patient, unemployed
      caregivers, and single- versus two-family caregivers (respite caregiving). Fifty
      one percent of the variance in caregiver burden was accounted for by the
      variables caregiver advanced age, higher caregiver hours, more caregiver physical
      health problems, higher levels of caregiver depressive symptoms, and more patient
      comorbidities. This article concludes with implications for nursing practice and
      future research.

PMID- 18612093
TI  - Application of the transtheoretical model to identify aspects influencing condom
      use among Korean college students.
AB  - Increasing condom use requires an understanding of the influencing factors.
      Previous research has used psychosocial theories such as the social cognitive
      theory and health belief to explain AIDS risk factors and condom use. However, it
      is still difficult to effectively predict the multidimensional factors associated
      with condom use. The present study utilizes the transtheoretical model to
      investigate condom use among college students by examining stages of change for
      condom use and measuring decisional balance and self-efficacy for each stage. The
      aim was to identify the variables affecting condom use so as to provide
      scientific data that would aid the development of effective strategies for
      increasing condom use.

PMID- 18612094
TI  - The light under the bushel basket: unpublished dissertations.

PMID- 18612095
TI  - Child health promotion and protection among Mexican mothers.
AB  - For numerous reasons, children of Mexican descent experience many health
      disparities. One strategy for addressing these disparities is to increase health
      promotion and protection behaviors that mothers use with their preschool
      children. Limited literature is available on such practices used by mothers of
      Mexican descent with their healthy preschool children. This study explored child
      health promotion and protection practices used by mothers of Mexican descent. A
      naturalistic design, guided by Spradley's ethnographic interview techniques, was
      selected for this study. The sample included 9 Mexican-descent mothers from an
      urban U.S. community with healthy preschool children. Despite significant
      challenges, participants promoted and protected the health of their preschool
      children by al cuidado (taking care) and by being al pendiente (being mindful) of
      balancing the health of their children's bodies, minds, and souls. Understanding
      these mothers' approaches allows the creation of culturally sensitive health
      programs that can build on existing maternal strengths.

PMID- 18612096
TI  - Regarding special issue on dementia care research.

PMID- 18612097
TI  - Response to the editorial "nursing science and dementia care".

PMID- 18612099
TI  - Dolichol biosynthesis and its effects on the unfolded protein response and
      abiotic stress resistance in Arabidopsis.
AB  - Dolichols are long-chain unsaturated polyisoprenoids with multiple cellular
      functions, such as serving as lipid carriers of sugars used for protein
      glycosylation, which affects protein trafficking in the endoplasmic reticulum.
      The biological functions of dolichols in plants are largely unknown. We isolated
      an Arabidopsis thaliana mutant, lew1 (for leaf wilting1), that showed a leaf
      wilting phenotype under normal growth conditions. LEW1 encoded a cis
      prenyltransferase, which when expressed in Escherichia coli catalyzed the
      formation of dolichol with a chain length around C(80) in an in vitro assay. The
      lew1 mutation reduced the total plant content of main dolichols by approximately
      85% and caused protein glycosylation defects. The mutation also impaired plasma
      membrane integrity, causing electrolyte leakage, lower turgor, reduced stomatal
      conductance, and increased drought resistance. Interestingly, drought stress in
      the lew1 mutant induced higher expression of the unfolded protein response
      pathway genes BINDING PROTEIN and BASIC DOMAIN/LEUCINE ZIPPER60 as well as
      earlier expression of the stress-responsive genes RD29A and COR47. The lew1
      mutant was more sensitive to dark treatment, but this dark sensitivity was
      suppressed by drought treatment. Our data suggest that LEW1 catalyzes dolichol
      biosynthesis and that dolichol is important for plant responses to endoplasmic
      reticulum stress, drought, and dark-induced senescence in Arabidopsis.

PMID- 18612100
TI  - Sphingolipid long-chain base hydroxylation is important for growth and regulation
      of sphingolipid content and composition in Arabidopsis.
AB  - Sphingolipids are structural components of endomembranes and function through
      their metabolites as bioactive regulators of cellular processes such as
      programmed cell death. A characteristic feature of plant sphingolipids is their
      high content of trihydroxy long-chain bases (LCBs) that are produced by the LCB C
      4 hydroxylase. To determine the functional significance of trihydroxy LCBs in
      plants, T-DNA double mutants and RNA interference suppression lines were
      generated for the two Arabidopsis thaliana LCB C-4 hydroxylase genes Sphingoid
      Base Hydroxylase1 (SBH1) and SBH2. These plants displayed reductions in growth
      that were dependent on the content of trihydroxy LCBs in sphingolipids. Double
      sbh1 sbh2 mutants, which completely lacked trihydroxy LCBs, were severely
      dwarfed, did not progress from vegetative to reproductive growth, and had
      enhanced expression of programmed cell death associated-genes. Furthermore, the
      total content of sphingolipids on a dry weight basis increased as the relative
      amounts of trihydroxy LCBs decreased. In trihydroxy LCB-null mutants,
      sphingolipid content was approximately 2.5-fold higher than that in wild-type
      plants. Increases in sphingolipid content resulted from the accumulation of
      molecular species with C16 fatty acids rather than with very-long-chain fatty
      acids, which are more commonly enriched in plant sphingolipids, and were
      accompanied by decreases in amounts of C16-containing species of chloroplast
      lipids. Overall, these results indicate that trihydroxy LCB synthesis plays a
      central role in maintaining growth and mediating the total content and fatty acid
      composition of sphingolipids in plants.

PMID- 18612101
TI  - The hematopoietic stem cell compartment of JAK2V617F-positive myeloproliferative
      disorders is a reflection of disease heterogeneity.
AB  - The JAK2V617F somatic point mutation has been described in patients with
      myeloproliferative disorders (MPDs). Despite this progress, it remains unknown
      how a single JAK2 mutation causes 3 different MPD phenotypes, polycythemia vera
      (PV), essential thrombocythemia, and primitive myelofibrosis (PMF). Using an in
      vivo xenotransplantation assay in nonobese diabetic-severe combined
      immunodeficient (NOD/SCID) mice, we tested whether disease heterogeneity was
      associated with quantitative or qualitative differences in the hematopoietic stem
      cell (HSC) compartment. We show that the HSC compartment of PV and PMF patients
      contains JAK2V617F-positive long-term, multipotent, and self-renewing cells.
      However, the proportion of JAK2V617F and JAK2 wild-type SCID repopulating cells
      was dramatically different in these diseases, without major modifications of the
      self-renewal and proliferation capacities for JAK2V617F SCID repopulating cells.
      These experiments provide new insights into the pathogenesis of JAK2V617F MPD and
      demonstrate that a JAK2 inhibitor needs to target the HSC compartment for optimal
      disease control in classical MPD.

PMID- 18612103
TI  - A prospective PETHEMA study of tandem autologous transplantation versus autograft
      followed by reduced-intensity conditioning allogeneic transplantation in newly
      diagnosed multiple myeloma.
AB  - One hundred ten patients with multiple myeloma (MM) failing to achieve at least
      near-complete remission (nCR) after a first autologous stem cell transplantation
      (ASCT) were scheduled to receive a second ASCT (85 patients) or a reduced
      intensity-conditioning allograft (allo-RIC; 25 patients), depending on the human
      leukocyte antigen (HLA)-identical sibling donor availability. There was a higher
      increase in complete remission (CR) rate (40% vs 11%, P = .001) and a trend
      toward a longer progression-free survival (PFS; median, 31 months vs not reached,
      P = .08) in favor of allo-RIC. In contrast, it was associated with a trend toward
      a higher transplantation-related mortality (16% vs 5%, P = .07), a 66% chance of
      chronic graft-versus-host disease and no statistical difference in event-free
      survival and overall survival. Although the PFS plateau observed with allo-RIC is
      very encouraging, this procedure is associated with high morbidity and mortality,
      and therefore it should still be considered investigational and restricted to
      well-designed prospective clinical trials. This trial is registered at
      ClinicalTrials.gov ID number NCT00560053.

PMID- 18612104
TI  - The glycoprotein Ib-IX-V complex contributes to tissue factor-independent
      thrombin generation by recombinant factor VIIa on the activated platelet surface.
AB  - Several lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able
      to activate factor X on an activated platelet, in a tissue factor-independent
      manner. We hypothesized that, besides the anionic surface, a receptor on the
      activated platelet surface is involved in this process. Here, we showed that, in
      an ELISA setup, a purified extracellular fragment of GPIbalpha bound to
      immobilized rFVIIa. Surface plasmon resonance established a affinity constant
      (K(d)) of approximately 20 nM for this interaction. In addition, CHO cells
      transfected with the GPIb-IX-V complex could adhere to immobilized rFVIIa,
      whereas wild-type CHO cells could not. Furthermore, platelets sti-mulated with a
      combination of collagen and thrombin adhered to immobilized rFVIIa under static
      conditions. Platelet adhesion was inhibited by treatment with O-sialoglycoprotein
      endopeptidase, which specifically cleaves GPIbalpha from the platelet surface. In
      addition, rFVIIa-mediated thrombin generation on the activated platelet surface
      was inhibited by cleaving GPIbalpha from its surface. In summary, 3 lines of
      evidence showed that rFVIIa interacts with the GPIb-IX-V complex, and this
      interaction enhanced tissue factor-independent thrombin generation mediated by
      rFVIIa on the activated platelet surface. The rFVIIa-GPIbalpha interaction could
      contribute to cessation of bleeding after administration of rFVIIa to patients
      with bleeding disorders.

PMID- 18612102
TI  - A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients
      with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic
      criteria (MRC/NCRI LY10 trial).
AB  - This prospective study aimed to develop reproducible diagnostic criteria for
      sporadic Burkitt lymphoma (BL), applicable to routine practice, and to evaluate
      the efficacy of dose-modified (dm) CODOX-M/IVAC in patients diagnosed using these
      criteria. The study was open to patients with an aggressive B-cell lymphoma with
      an MKI67 fraction approaching 100%. Immunophenotype and fluorescent in situ
      hybridization (FISH) were used to separate BL from other aggressive B-cell
      lymphomas. BL was characterized by the presence of a cMYC rearrangement as a sole
      cytogenetic abnormality occurring in patients with a germinal center phenotype
      with absence of BCL-2 expression and abnormal TP53 expression. A total of 128
      patients were eligible for the study, of whom 58 were considered to have BL and
      70 to have diffuse large B-cell lymphoma (DLBCL). There were 110 clinically fit
      patients who received dmCODOX-M (methotrexate, dose 3 g/m(2)) with or without
      IVAC according to risk group. The 2-year progression-free survival was 64% (95%
      confidence interval [CI] 51%-77%) for BL, 55% (95% CI 42%-66%) for DLBCL, 85%
      (95% CI 73%-97%) for low risk, and 49% (95% CI 38%-60%) for high-risk patients.
      The observed differences in outcome and other clinical features validate the
      proposed diagnostic criteria. Compared with the previous trial LY06 with full
      dose methotrexate (6.7 g/m(2)), there was a reduction in toxicity with comparable
      outcomes. This study was registered at www.clinicaltrials.gov as NCT00040690.

PMID- 18612105
TI  - The cover. Bathing, Marblehead.

PMID- 18612106
TI  - A medical humanist says good-bye.

PMID- 18612107
TI  - Studies explore factors that underlie varied responses to cancer drugs.

PMID- 18612108
TI  - FDA turns to electronic "sentinel" to flag prescription drug safety problems.

PMID- 18612109
TI  - Practice parameter: simple maneuver is best therapy for common form of vertigo.

PMID- 18612110
TI  - States show wide discrepancies in quality of health care for US children.

PMID- 18612111
TI  - Preterm birth, long-term survival, and fertility.

PMID- 18612112
TI  - Homocysteine levels, paraoxonase 1 (PON1) activity, and cardiovascular risk.

PMID- 18612113
TI  - Germline genomic homozygosity and cancer risk.

PMID- 18612114
TI  - Survival following primary androgen deprivation therapy among men with localized
      prostate cancer.
AB  - CONTEXT: Despite a lack of data, increasing numbers of patients are receiving
      primary androgen deprivation therapy (PADT) as an alternative to surgery,
      radiation, or conservative management for the treatment of localized prostate
      cancer. OBJECTIVE: To evaluate the association between PADT and survival in
      elderly men with localized prostate cancer. DESIGN, SETTING, AND PATIENTS: A
      population-based cohort study of 19,271 men aged 66 years or older receiving
      Medicare who did not receive definitive local therapy for clinical stage T1-T2
      prostate cancer. These patients were diagnosed in 1992-2002 within predefined US
      geographical areas, with follow-up through December 31, 2006, for all-cause
      mortality and through December 31, 2004, for prostate cancer-specific mortality.
      Instrumental variable analysis was used to address potential biases associated
      with unmeasured confounding variables. MAIN OUTCOME MEASURES: Prostate cancer
      specific survival and overall survival. RESULTS: Among patients with localized
      prostate cancer (median age, 77 years), 7867 (41%) received PADT, and 11,404 were
      treated with conservative management, not including PADT. During the follow-up
      period, there were 1560 prostate cancer deaths and 11,045 deaths from all causes.
      Primary androgen deprivation therapy was associated with lower 10-year prostate
      cancer-specific survival (80.1% vs 82.6%; hazard ratio [HR], 1.17; 95% confidence
      interval [CI], 1.03-1.33) and no increase in 10-year overall survival (30.2% vs
      30.3%; HR, 1.00; 95% CI, 0.96-1.05) compared with conservative management.
      However, in a prespecified subset analysis, PADT use in men with poorly
      differentiated cancer was associated with improved prostate cancer-specific
      survival (59.8% vs 54.3%; HR, 0.84; 95% CI, 0.70-1.00; P = .049) but not overall
      survival (17.3% vs 15.3%; HR, 0.92; 95% CI, 0.84-1.01). CONCLUSION: Primary
      androgen deprivation therapy is not associated with improved survival among the
      majority of elderly men with localized prostate cancer when compared with
      conservative management.

PMID- 18612115
TI  - Fetuin-A and incident diabetes mellitus in older persons.
AB  - CONTEXT: Fetuin-A is a hepatic secretory protein that binds the insulin receptor
      and inhibits insulin action in vitro. In prior cross-sectional studies in humans,
      higher fetuin-A levels were associated with insulin resistance. However, the
      longitudinal association of fetuin-A with incident type 2 diabetes mellitus is
      unknown. OBJECTIVE: To determine whether fetuin-A levels are associated with
      incident diabetes in older persons. DESIGN, SETTING, AND PARTICIPANTS:
      Observational study among 3075 well-functioning persons aged 70 to 79 years. In
      this case-cohort study, we retrospectively measured fetuin-A levels in baseline
      serum among 406 randomly selected participants without prevalent diabetes, and
      all participants who developed incident diabetes mellitus during a 6-year follow
      up (to August 31, 2005). MAIN OUTCOME MEASURE: Incident diabetes mellitus.
      RESULTS: Incident diabetes developed in 135 participants (10.1 cases/1000 person
      years). Participants with fetuin-A levels within the highest tertile (> 0.97 g/L)
      had an increased risk of incident diabetes (13.3 cases/1000 person-years)
      compared with participants in the lowest tertile (< or = 0.76 g/L) (6.5
      cases/1000 person-years) in models adjusted for age, sex, race, waist
      circumference, body weight, physical activity, blood pressure level, fasting
      glucose level, high-density lipoprotein cholesterol concentration, triglyceride
      concentration, and C-reactive protein level (adjusted hazard ratio, 2.41; 95%
      confidence interval, 1.28-4.53; P = .007). The association was not affected by
      adipocytokine levels but was moderately attenuated by adjustment for visceral
      adiposity (adjusted hazard ratio of highest vs lowest tertile 1.72; 95%
      confidence interval, 0.98-3.05; P = .06). CONCLUSION: Among well-functioning
      older persons, serum fetuin-A is associated with incident diabetes, independent
      of other markers of insulin resistance.

PMID- 18612116
TI  - Association between the Medicare Modernization Act of 2003 and patient wait times
      and travel distance for chemotherapy.
AB  - CONTEXT: The Medicare Prescription Drug, Improvement, and Modernization Act of
      2003 (MMA) altered reimbursements for outpatient chemotherapy drugs and drug
      administration services. Anecdotal reports suggest that these adjustments may
      have negatively affected access to chemotherapy for Medicare beneficiaries.
      OBJECTIVE: To compare patient wait times and travel distances for chemotherapy
      before and after the enactment of the MMA. DESIGN, SETTING, AND PATIENTS:
      Analysis of a nationally representative 5% sample of claims from the Centers for
      Medicare & Medicaid Services for the period 2003 through 2006. Patients were
      Medicare beneficiaries with incident breast cancer, colorectal cancer, leukemia,
      lung cancer, or lymphoma who received chemotherapy in inpatient hospital,
      institutional outpatient, or physician office settings. MAIN OUTCOME MEASURES:
      Days from incident diagnosis to first chemotherapy visit and distance traveled
      for treatment, controlling for age, sex, race/ethnicity, cancer type, geographic
      region, comorbid conditions, and year of diagnosis and treatment. RESULTS: There
      were 5082 incident cases of breast cancer, colorectal cancer, leukemia, lung
      cancer, or lymphoma in 2003; 5379 cases in 2004; 5116 cases in 2005; and 5288
      cases in 2006. Approximately 70% of patients received treatment in physician
      office settings in each year. Although the distribution of treatment settings in
      2004 and 2005 was not significantly different from 2003 (P = .24 and P = .72,
      respectively), there was a small but significant change from 2003 to 2006 (P =
      .02). The proportion of patients receiving chemotherapy in inpatient settings
      decreased from 10.2% in 2003 to 8.8% in 2006 (P = .03), and the proportion in
      institutional outpatient settings increased from 21.1% to 22.5% (P = .004). The
      proportion in physician offices remained at 68.7% (P = .29). The median time from
      diagnosis to initial chemotherapy visit was 28 days in 2003, 27 days in 2004, 29
      days in 2005, and 28 days in 2006. In multivariate analyses, average wait times
      for chemotherapy were 1.96 days longer in 2005 than in 2003 (95% confidence
      interval [CI], 0.11-3.80 days; P = .04) but not significantly different in 2006
      (0.88 days; 95% CI, -0.96 to 2.71 days; P = .35). Median travel distance was 7
      miles (11.2 km) in 2003 and 8 miles (12.8 km) in 2004 through 2006. After
      adjustment, average travel distance remained slightly longer in 2004 (1.47 miles
      [2.35 km]; 95% CI, 0.87-2.07 miles [1.39-3.31 km]; P < .001), 2005 (1.19 miles
      [1.90 km]; 95% CI, 0.58-1.80 miles [0.93-2.88 km]; P < .001), and 2006 (1.30
      miles [2.08 km]; 95% CI, 0.69-1.90 miles [1.10-3.04 km]; P < .001) compared with
      2003. CONCLUSION: There have not been major changes in travel distance and
      patient wait times for chemotherapy in the Medicare population since 2003, the
      year before MMA-related changes in reimbursement.

PMID- 18612118
TI  - Exposing poverty and inspiring medical humanitarianism.

PMID- 18612117
TI  - Ankle brachial index combined with Framingham Risk Score to predict
      cardiovascular events and mortality: a meta-analysis.
AB  - CONTEXT: Prediction models to identify healthy individuals at high risk of
      cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is
      an indicator of atherosclerosis and has the potential to improve prediction.
      OBJECTIVE: To determine if the ABI provides information on the risk of
      cardiovascular events and mortality independently of the Framingham risk score
      (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were
      identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to
      February 2008) was conducted using common text words for the term ankle brachial
      index combined with text words and Medical Subject Headings to capture
      prospective cohort designs. Review of reference lists and conference proceedings,
      and correspondence with experts was conducted to identify additional published
      and unpublished studies. STUDY SELECTION: Studies were included if participants
      were derived from a general population, ABI was measured at baseline, and
      individuals were followed up to detect total and cardiovascular mortality. DATA
      EXTRACTION: Prespecified data on individuals in each selected study were
      extracted into a combined data set and an individual participant data meta
      analysis was conducted on individuals who had no previous history of coronary
      heart disease. RESULTS: Sixteen population cohort studies fulfilling the
      inclusion criteria were included. During 480,325 person-years of follow-up of
      24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped
      distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year
      cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95%
      confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4%
      (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding
      mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%)
      (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS
      (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (<
      or = 0.90) was associated with approximately twice the 10-year total mortality,
      cardiovascular mortality, and major coronary event rate compared with the overall
      rate in each FRS category. Inclusion of the ABI in cardiovascular risk
      stratification using the FRS would result in reclassification of the risk
      category and modification of treatment recommendations in approximately 19% of
      men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy
      of cardiovascular risk prediction beyond the FRS.

PMID- 18612119
TI  - Health policy and public trust.

PMID- 18612120
TI  - Web searching for information about physicians.

PMID- 18612121
TI  - JAMA patient page. Prostate cancer.

PMID- 18612122
TI  - Ontario institute offers new model of cancer research.

PMID- 18612123
TI  - Forensic bioinformatician aims to solve mysteries of biomarker studies.

PMID- 18612124
TI  - Man's best friend is also a friend of cancer research.

PMID- 18612125
TI  - The Kanzius machine: a new cancer treatment idea from an unexpected source.

PMID- 18612126
TI  - StatBite: Hepatitis C virus-related hepatocellular carcinoma incidence among men
      in Osaka.

PMID- 18612127
TI  - Cancer as a ferrotoxic disease: are we getting hard stainless evidence?

PMID- 18612128
TI  - Gauging the performance of SNPs, biomarkers, and clinical factors for predicting
      risk of breast cancer.

PMID- 18612129
TI  - Multiple cellular mechanisms related to cyclin A1 in prostate cancer invasion and
      metastasis.
AB  - BACKGROUND: Cyclin A1 is a cell cycle regulator that has been implicated in the
      progression of prostate cancer. Its role in invasion and metastasis of this
      disease has not been characterized. METHODS: Immunohistochemistry and cDNA
      microarray analyses were used to assess protein and mRNA expression of cyclin A1
      and proteins with roles in metastasis, including vascular endothelial growth
      factor (VEGF), metalloproteinase 2 (MMP2), and MMP9, in human prostate cancer.
      Transient transfection and infection with viral vectors expressing cyclin A1 and
      short hairpin RNA (shRNA) targeting cyclin A1 were used to study the effects of
      altered cyclin A1 expression in PC3 prostate cancer cells. The BrdU assay,
      annexin V staining, and invasion chambers were used to examine cyclin A1 effects
      on proliferation, apoptosis, and invasion, respectively. The role of cyclin A1
      and androgen receptor (AR) in transcription of VEGF and MMP2 was assessed by
      promoter mutation and chromatin immunoprecipitation. The effect of cyclin A1
      expression on tumor growth and metastasis was analyzed in a mouse model of
      metastasis. All statistical tests were two-sided. RESULTS: Cyclin A1 protein and
      mRNA expression were statistically significantly higher in prostate cancers than
      in adjacent benign tissues. A statistically significant correlation between
      expression of cyclin A1 and of MMP2, MMP9, and VEGF was observed in prostate
      tumors from 482 patients (P values from Spearman rank correlation tests < .001).
      PC3 cells that overexpressed cyclin A1 showed increased invasiveness, and
      inhibition of cyclin A1 expression via shRNA expression reduced invasiveness of
      these cells. Eight of 10 mice (80%) bearing PC3 cells overexpressing cyclin A1
      had infiltration of tumor cells in lymph node, liver, and lung, but all 10 mice
      bearing tumors expressing control vector were free of liver and lung metastases
      and only one mouse from this group had lymph node metastasis (P values from
      Fisher exact tests < .001). Cyclin A1, in concert with AR, bound to and increased
      expression from the VEGF and MMP2 promoters. CONCLUSIONS: Cyclin A1 contributes
      to prostate cancer invasion by modulating the expression of MMPs and VEGF and by
      interacting with AR.

PMID- 18612130
TI  - Decreased cancer risk after iron reduction in patients with peripheral arterial
      disease: results from a randomized trial.
AB  - BACKGROUND: Excess iron has been implicated in cancer risk through increased iron
      catalyzed free radical-mediated oxidative stress. METHODS: A multicenter
      randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410)
      tested the hypothesis that reducing iron stores by phlebotomy would influence
      vascular outcomes in patients with peripheral arterial disease. Patients without
      a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to
      control (n = 641) or iron reduction (n = 636). Occurrence of new visceral
      malignancy and cause-specific mortality data were collected prospectively. Cancer
      and mortality outcomes in the two arms were compared using intent-to-treat
      analysis with a Cox proportional hazards regression model. Statistical tests were
      two-sided. RESULTS: Patients were followed up for an average of 4.5 years.
      Ferritin levels were similar in both groups at baseline but were lower in iron
      reduction patients than control patients across all 6-month visits (mean = 79.7
      ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI =
      115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the
      iron reduction group than in the control group (38 vs 60, hazard ratio [HR] =
      0.65, 95% CI = 0.43 to 0.97; P = .036), and, among patients with new cancers,
      those in the iron reduction group had lower cancer-specific and all-cause
      mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI =
      0.29 to 0.83; P = .009, respectively) than those in the control group. Mean
      ferritin levels across all 6-monthly visits were similar in patients in the iron
      reduction and control groups who developed cancer but were lower among all
      patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI
      = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017).
      CONCLUSIONS: Iron reduction was associated with lower cancer risk and mortality.
      Further studies are needed to define the role of body iron in cancer risk.

PMID- 18612131
TI  - Disenrollment from Medicare managed care among beneficiaries with and without a
      cancer diagnosis.
AB  - BACKGROUND: Medicare managed care may offer enrollees lower out-of-pocket costs
      and provide benefits that are not available in the traditional fee-for-service
      Medicare program. However, managed care plans may also restrict provider choice
      in an effort to control costs. We compared rates of voluntary disenrollment from
      Medicare managed care to traditional fee-for-service Medicare among Medicare
      managed care enrollees with and without a cancer diagnosis. METHODS: We
      identified Medicare managed care enrollees aged 65 years or older who were
      diagnosed with a first primary breast (n = 28 331), colorectal (n = 26 494),
      prostate (n = 29 046), or lung (n = 31 243) cancer from January 1, 1995, through
      December 31, 2002, in Surveillance, Epidemiology, and End Results (SEER) cancer
      registry records linked with Medicare enrollment files. Cancer patients were pair
      matched to cancer-free enrollees by age, sex, race, and geographic location. We
      estimated rates of voluntary disenrollment to fee-for-service Medicare in the 2
      years after each cancer patient's diagnosis, adjusted for plan characteristics
      and Medicare managed care penetration, by use of Cox proportional hazards
      regression. RESULTS: In the 2 years after diagnosis, cancer patients were less
      likely to disenroll from Medicare managed care than their matched cancer-free
      peers (for breast cancer, adjusted hazard ratio [HR] for disenrollment = 0.78,
      95% confidence interval [CI] = 0.74 to 0.82; for colorectal cancer, HR = 0.84,
      95% CI = 0.80 to 0.88; for prostate cancer, HR = 0.86, 95% CI = 0.82 to 0.90; and
      for lung cancer, HR = 0.81, 95% CI = 0.76 to 0.86). Results were consistent
      across strata of age, sex, race, SEER registry, and cancer stage. CONCLUSION: A
      new cancer diagnosis between 1995 and 2002 did not precipitate voluntary
      disenrollment from Medicare managed care to traditional fee-for-service Medicare.

PMID- 18612133
TI  - Computed tomography screening for lung cancer in a high-risk population: update
      on current status.

PMID- 18612132
TI  - Secular trends in mortality from common cancers in the United States by
      educational attainment, 1993-2001.
AB  - BACKGROUND: Death rates for the four major cancer sites (lung, breast, prostate,
      and colon and rectum) have declined steadily in the United States among persons
      aged 25-64 years since the early 1990s. We used national data to examine these
      trends in relation to educational attainment. METHODS: We calculated age
      standardized death rates for each of the four cancers by level of education among
      25- to 64-year-old non-Hispanic white and non-Hispanic black men and women for
      1993 through 2001 using data on approximately 86% of US deaths from the National
      Center for Health Statistics, education level as recorded on the death
      certificate, and population data from the US Bureau of Census Current Population
      Survey. Annual percent changes in age-adjusted death rates were estimated using
      weighted log-linear regression models. All statistical tests were two-sided.
      RESULTS: Death rates for each cancer decreased statistically significantly from
      1993 to 2001 in people with at least 16 years of education in every sex and race
      stratum except lung cancer in black women, for whom death rates were stable. For
      example, colorectal cancer death rates among white men, black men, white women,
      and black women with at least 16 years of education decreased by 2.4% (P < .001),
      4.8% (P = .011), 3.0% (P < .001), and 2.6% (P = .030) annually, respectively. By
      contrast, among people with less than 12 years of education, a statistically
      significant decrease in death rates from 1993 through 2001 was seen only for
      breast cancer in white women (1.4% per year; P = .029). Death rates among persons
      with less than 12 years of education over the same time interval increased for
      lung cancer in white women (2.4% per year; P < .001) and for colon cancer in
      black men (2.7% per year; P < .001) and were stable for the remaining
      race/sex/site strata. Temporal trends generally followed an educational gradient
      in which the slopes of the decreases in death rate became steeper with higher
      educational attainment. CONCLUSION: The recent declines in death rates from major
      cancers in the United States mainly reflect declines in more highly educated
      individuals.

PMID- 18612134
TI  - Reduced expression of cyclooxygenase-2 in primary breast cancer.

PMID- 18612135
TI  - False-positive results in cancer epidemiology: a plea for epistemological
      modesty.
AB  - False-positive results are inherent in the scientific process of testing
      hypotheses concerning the determinants of cancer and other human illnesses.
      Although much of what is known about the etiology of human cancers has arisen
      from well-conducted epidemiological studies, epidemiology has been increasingly
      criticized for producing findings that are often sensationalized in the media and
      fail to be upheld in subsequent studies. Herein we describe examples from cancer
      epidemiology of likely false-positive findings and discuss conditions under which
      such results may occur. We suggest general guidelines or principles, including
      the endorsement of editorial policies requiring the prominent listing of study
      caveats, which may help reduce the reporting of misleading results. Increased
      epistemological humility regarding findings in epidemiology would go a long way
      to diminishing the detrimental effects of false-positive results on the
      allocation of limited research resources, on the advancement of knowledge of the
      causes and prevention of cancer, and on the scientific reputation of epidemiology
      and would help to prevent oversimplified interpretations of results by the media
      and the public.

PMID- 18612136
TI  - Discriminatory accuracy from single-nucleotide polymorphisms in models to predict
      breast cancer risk.
AB  - One purpose for seeking common alleles that are associated with disease is to use
      them to improve models for projecting individualized disease risk. Two genome
      wide association studies and a study of candidate genes recently identified seven
      common single-nucleotide polymorphisms (SNPs) that were associated with breast
      cancer risk in independent samples. These seven SNPs were located in FGFR2, TNRC9
      (now known as TOX3), MAP3K1, LSP1, CASP8, chromosomal region 8q, and chromosomal
      region 2q35. I used estimates of relative risks and allele frequencies from these
      studies to estimate how much these SNPs could improve discriminatory accuracy
      measured as the area under the receiver operating characteristic curve (AUC). A
      model with these seven SNPs (AUC = 0.574) and a hypothetical model with 14 such
      SNPs (AUC = 0.604) have less discriminatory accuracy than a model, the National
      Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT), that is based on
      ages at menarche and at first live birth, family history of breast cancer, and
      history of breast biopsy examinations (AUC = 0.607). Adding the seven SNPs to
      BCRAT improved discriminatory accuracy to an AUC of 0.632, which was, however,
      less than the improvement from adding mammographic density. Thus, these seven
      common alleles provide less discriminatory accuracy than BCRAT but have the
      potential to improve the discriminatory accuracy of BCRAT modestly. Experience to
      date and quantitative arguments indicate that a huge increase in the numbers of
      case patients with breast cancer and control subjects would be required in genome
      wide association studies to find enough SNPs to achieve high discriminatory
      accuracy.

PMID- 18612137
TI  - Innovation!

PMID- 18612139
TI  - Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry,
      antiinflammatory and protective effects in vitro and in vivo, and future
      perspectives for the treatment of immune-mediated inflammatory diseases.
AB  - Alpha-MSH is a tridecapeptide derived from proopiomelanocortin. Many studies over
      the last few years have provided evidence that alpha-MSH has potent protective
      and antiinflammatory effects. These effects can be elicited via centrally
      expressed melanocortin receptors that orchestrate descending neurogenic
      antiinflammatory pathways. alpha-MSH can also exert antiinflammatory and
      protective effects on cells of the immune system and on peripheral nonimmune cell
      types expressing melanocortin receptors. At the molecular level, alpha-MSH
      affects various pathways implicated in regulation of inflammation and protection,
      i.e., nuclear factor-kappaB activation, expression of adhesion molecules and
      chemokine receptors, production of proinflammatory cytokines and mediators, IL-10
      synthesis, T cell proliferation and activity, inflammatory cell migration,
      expression of antioxidative enzymes, and apoptosis. The antiinflammatory effects
      of alpha-MSH have been validated in animal models of experimentally induced
      fever; irritant and allergic contact dermatitis, vasculitis, and fibrosis;
      ocular, gastrointestinal, brain, and allergic airway inflammation; and arthritis,
      but also in models of organ injury. One obstacle limiting the use of alpha-MSH in
      inflammatory disorders is its pigmentary effect. Due to its preserved
      antiinflammatory effect but lack of pigmentary action, the C-terminal tripeptide
      of alpha-MSH, KPV, has been delineated as an alternative for antiinflammatory
      therapy. KdPT, a derivative of KPV corresponding to amino acids 193-195 of IL
      1beta, is also emerging as a tripeptide with antiinflammatory effects. The
      physiochemical properties and expected low costs of production render both agents
      suitable for the future treatment of immune-mediated inflammatory skin and bowel
      disease, fibrosis, allergic and inflammatory lung disease, ocular inflammation,
      and arthritis.

PMID- 18612140
TI  - The cytoplasmic tail of MUC1: a very busy place.
AB  - The role of mucin 1 (MUC1) in protecting epithelia from microbial infection,
      enzymatic digestion, and other irritants has been appreciated for some time. In
      addition, MUC1 serves as a barrier to embryo implantation. MUC1 is highly
      abundant in many tumors in which its role in barrier function may serve to
      protect cells from the host immune system, whereas MUC1 is less abundant in
      certain other cells-for example, in trophoblasts and hematopoietic cells. Most of
      the functions of MUC1 depend upon its large, extracellular ectodomain.
      Nonetheless, a series of studies have demonstrated a surprisingly diverse role
      for the small, highly conserved cytoplasmic domain of MUC1 in intracellular
      signaling. These intracellular activities have potential roles in the physiology
      of both malignant and nonmalignant cells.

PMID- 18612141
TI  - Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase
      independent biological activities.
AB  - Over the past 20 years, the tissue inhibitors of metalloproteinases (TIMPs) have
      been implicated in direct regulation of cell growth and apoptosis. However, the
      mechanisms of these effects have been controversial. Recent work by several
      laboratories has identified specific signaling pathways and cell surface binding
      partners for members of the TIMP family. TIMP-2 binding to the integrin
      alpha(3)beta(1) is the first description of a cell surface receptor for a TIMP
      family member. TIMP-2 has been shown to induce gene expression, to promote G(1)
      cell cycle arrest, and to inhibit cell migration. TIMP-1 binding to CD63 inhibits
      cell growth and apoptosis. These new findings suggest that TIMPs are
      multifunctional and can act either directly through cell surface receptors or
      indirectly through modulation of protease activity to direct cell fate. The
      emerging concept is that TIMPs function in a contextual fashion so that the
      mechanism of action depends on the tissue microenvironment.

PMID- 18612142
TI  - Manual stimulation of the suprahyoid-sublingual region diminishes polynnervation
      of the motor endplates and improves recovery of function after hypoglossal nerve
      injury in rats.
AB  - BACKGROUND: Using the rat facial nerve axotomy model, the authors recently showed
      that manual stimulation of denervated whiskerpad muscles reduced the
      posttransectional polyinnervation at the neuromuscular junctions and promoted
      full recovery of vibrissal whisking. OBJECTIVE: Prompted by implications for
      rehabilitation therapy, the authors examined whether manual stimulation of
      denervated supra- and infrahyoid muscles would also improve recovery after
      unilateral lesion on the hypoglossal nerve. METHODS: Adult rats underwent
      transection of the right hypoglossal nerve. Half of the animals received no
      postoperative treatment, and the other half were subjected to daily manual
      stimulation of the suprahyoid/sublingual region for 2 months. Recovery was
      assessed by measuring the angle of tongue-tip deviation from the midline, degree
      of collateral axonal branching at the lesion site (counts after retrograde
      labeling with 2 fluorescent dyes), synaptic input to the hypoglossal motoneurons
      using synaptophysin immunocytochemistry, tongue-muscles motor representation in
      the cerebral cortex after c-Fos immunocytochemistry, and portion of
      polyinnervated neuromuscular junctions. RESULTS: In animals receiving manual
      stimulation, the tongue-tip deviation was 37.0 +/- 49.37 degrees , whereas values
      in control nonstimulated rats were significantly higher (50.1 +/- 9.01 degrees ;
      P < .05; mean +/- SD). Improved recovery was not associated with reduced
      collateral axonal branching; there were also no differences in tongue-muscles
      representation in the motor cortex. However, manual stimulation restored the
      total synaptic input to levels in intact animals and reduced the proportion of
      polyinnervated neuromuscular junctions compared with nonstimulated animals.
      CONCLUSION: The data show that manual stimulation of denervated muscles improves
      functional outcome following peripheral nerve injury. This suggests immediate
      potential for enhancing clinical rehabilitation strategies.

PMID- 18612143
TI  - siRNA screening reveals JNK2 as an evolutionary conserved regulator of
      triglyceride homeostasis.
AB  - Lipid homeostasis is essential for proper function of cells and organisms. To
      unravel new regulators of this system, we developed a screening procedure,
      combining RNA interference in HeLa cells and TLC, which enabled us to monitor
      modifications of lipid composition resulting from short, interfering RNA knock
      downs. We applied this technique to the analysis of 600 human kinases. Despite
      the occurrence of off-target effects, we identified JNK2 as a new player in
      triglyceride (TG) homeostasis and lipid droplet metabolism and, more
      specifically, in the regulation of lipolysis. Similar control of the level of TGs
      and lipid droplets was observed for its Schizosaccharomyces pombe homolog, Sty1,
      suggesting an evolutionary conserved function of mitogen-activated protein
      kinases in the regulation of lipid storage in eukaryotic cells.

PMID- 18612144
TI  - Chemotherapy for the treatment of children and adolescents with malignant germ
      cell tumors.

PMID- 18612145
TI  - Host-related factors in breast cancer: an underappreciated piece of the puzzle?

PMID- 18612146
TI  - Breast cancer in young women: a new color or a different shade of pink?

PMID- 18612147
TI  - Risk factors for the incidence of breast cancer: do they affect survival from the
      disease?
AB  - PURPOSE: Risk factors that influence the incidence of breast cancer may also
      affect survival after diagnosis. METHODS: Data from 4,560 women with invasive
      breast cancer who had taken part in the population-based Studies of Epidemiology
      and Risk Factors in Cancer Heredity (SEARCH) breast cancer study were used to
      investigate the influence on survival of variables related to pregnancy, menarche
      and menopause, prior use of exogenous hormones, height, weight, body mass index
      (BMI), smoking history, and alcohol intake. RESULTS: In univariate analyses,
      there was no association between prognosis and age at menarche and menopause,
      menopausal status at diagnosis, smoking history, or prior use of the oral
      contraceptive pill. Women whose most recent pregnancy was more than 30 years ago
      had a 35% reduced risk of dying (95% CI, 8% to 54%) compared with women who had a
      full-term pregnancy in the past 15 years, and the use of hormone replacement
      therapy for more than 4 years was associated with a similar risk reduction. BMI
      was associated with a 3% (95% CI, 1% to 4%) increase in mortality per unit
      increase. Improved prognosis was seen with increasing current alcohol
      consumption, with a 2% (95% CI, 1% to 3%) reduction in the risk of death per unit
      of alcohol consumed per week. CONCLUSION: The apparent benefit of alcohol intake
      has not been described before, and our data need to be interpreted with some
      caution. However, our finding that an increase in BMI is associated with a poorer
      prognosis supports previously published data and suggests that advice on weight
      loss should be given to all obese patients with breast cancer.

PMID- 18612148
TI  - Young age at diagnosis correlates with worse prognosis and defines a subset of
      breast cancers with shared patterns of gene expression.
AB  - PURPOSE: Breast cancer arising in young women is correlated with inferior
      survival and higher incidence of negative clinicopathologic features. The biology
      driving this aggressive disease has yet to be defined. PATIENTS AND METHODS:
      Clinically annotated, microarray data from 784 early-stage breast cancers were
      identified, and prospectively defined, age-specific cohorts (young: </= 45 years,
      n = 200; older: >/= 65 years, n = 211) were compared by prognosis,
      clinicopathologic variables, mRNA expression values, single-gene analysis, and
      gene set enrichment analysis (GSEA). Univariate and multivariate analyses were
      performed. RESULTS: Using clinicopathologic variables, young women illustrated
      lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027),
      larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2)
      overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade
      tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard
      ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in
      young women had significantly lower ERalpha mRNA (P < .0001), ERbeta (P = .02),
      and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P <
      .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001).
      Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets
      significantly distinguishing breast tumors arising in young women. Combining
      clinicopathologic and genomic variables among tumors arising in young women
      demonstrated that younger age and lower ERbeta and higher EGFR mRNA expression
      were significant predictors of inferior DFS. CONCLUSION: This large-scale genomic
      analysis illustrates that breast cancer arising in young women is a unique
      biologic entity driven by unifying oncogenic signaling pathways, is characterized
      by less hormone sensitivity and higher HER-2/EGFR expression, and warrants
      further study to offer this poor-prognosis group of women better preventative and
      therapeutic options.

PMID- 18612149
TI  - Effect of esthetic outcome after breast-conserving surgery on psychosocial
      functioning and quality of life.
AB  - PURPOSE: Although breast-conserving surgery (BCS) is often assumed to result in
      minimal deformity, many patients report postoperative breast asymmetry.
      Understanding the effect of asymmetry on psychosocial functioning is essential
      for patients to make an informed choice for surgery. PATIENTS AND METHODS: All
      women who underwent BCS at the University of Michigan Medical Center (Ann Arbor,
      MI) during a 4-year period were surveyed using a mailed questionnaire (N = 714;
      response rate = 79.5%). Women were queried regarding five aspects of psychosocial
      functioning: quality of life (QOL), depression, fear of recurrence,
      stigmatization, and perceived change in health status. Postoperative breast
      asymmetry was assessed using items from the Breast Cancer Treatment and Outcomes
      Survey. Multiple regression was used to examine the relationship between breast
      asymmetry and each outcome, controlling for age, time from surgery in years,
      race, education level, disease stage, surgical treatment, and the occurrence of
      postoperative complications. RESULTS: Women with pronounced breast asymmetry were
      significantly more likely to feel stigmatized as a result of their breast cancer
      treatment (odds ratio [OR] = 4.58; 95% CI, 2.77 to 7.55) and less likely to
      report unchanged or improved health after treatment (OR = 0.43; 95% CI, 0.27 to
      0.66). Minimal breast asymmetry was associated with higher QOL scores (86.3 v
      82.4, P < .001). Finally, women with pronounced breast asymmetry were more likely
      to exhibit depressive symptoms (minimal asymmetry, 16.2%; moderate asymmetry,
      18.0%; pronounced asymmetry, 33.7%, Wald test = 16.6; P = .002). CONCLUSION:
      Pronounced breast asymmetry after BCS is significantly correlated with poor
      psychosocial functioning. Identifying patients at risk for postoperative
      asymmetry at the time of consultation may allow for improved referral for
      supportive counseling, prosthetics, and reconstruction.

PMID- 18612150
TI  - Novel intraoperative molecular test for sentinel lymph node metastases in
      patients with early-stage breast cancer.
AB  - PURPOSE: An accurate, intraoperative sentinel lymph node (SLN) test could
      decrease delayed axillary dissections. Molecular tests may be more sensitive than
      current intraoperative tests but historically have not been rapid enough and have
      not been properly validated. We present the results from a large, prospective
      evaluation of the first rapid molecular SLN test, the Breast Lymph Node (BLN)
      Assay. METHODS: A beta trial (n = 304) to determine the threshold levels of
      mammaglobin and cytokeratin 19 correlating with metastasis greater than 0.2 mm
      and a validation trial (n = 416) to validate the threshold cutoffs were
      conducted. Alternating portions from each SLN were processed for histology and
      the BLN Assay. RESULTS: BLN Assay performance against extensive permanent-section
      histology verified by central pathology review was similar to that expected of
      standard permanent-section histology: sensitivity, 87.6%; specificity, 94.2%;
      positive predictive value, 86.2%; and negative predictive value (NPV), 94.9%. In
      319 patients with both frozen-section hematoxylin and eosin results and BLN Assay
      results, the BLN Assay had higher sensitivity (95.6%) and NPV (98.2%) than frozen
      section (sensitivity, 85.6%; NPV, 94.5%). The assay can be performed in
      approximately 36 to 46 minutes for one to three nodes. CONCLUSION: The BLN Assay
      allows a rapid evaluation of 50% of each SLN. Comparison with permanent-section
      histology on adjacent node pieces evaluated by expert pathologists indicated that
      the BLN Assay was more sensitive than current intraoperative techniques while
      maintaining high specificity. These data indicate that the assay may be
      clinically useful for intraoperative or postoperative axillary lymph node
      dissection decisions.

PMID- 18612151
TI  - Increased EGFR gene copy number detected by fluorescent in situ hybridization
      predicts outcome in non-small-cell lung cancer patients treated with cetuximab
      and chemotherapy.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) gene copy number detected by
      fluorescent in situ hybridization (FISH) has proven to be useful for selection of
      non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine
      kinase inhibitors. Here, we evaluate EGFR FISH as a predictive marker in NSCLC
      patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus
      chemotherapy. PATIENTS AND METHODS: Two hundred twenty-nine chemotherapy-naive
      patients with advanced-stage NSCLC were enrolled onto a phase II selection trial
      evaluating sequential or concurrent chemotherapy (paclitaxel plus carboplatin)
      with cetuximab. RESULTS: EGFR FISH was assessable in 76 patients with available
      tumor tissue and classified as positive (four or more gene copies per cell in >/=
      40% of the cells or gene amplification) in 59.2%. Response (complete
      response/partial response) was numerically higher in FISH-positive (45%) versus
      FISH-negative (26%) patients (P = .14), whereas disease control rate (complete
      response/partial response plus stable disease) was statistically superior (81% v
      55%, respectively; P = .02). Patients with FISH-positive tumors had a median
      progression-free survival time of 6 months compared with 3 months for FISH
      negative patients (P = .0008). Median survival time was 15 months for the FISH
      positive group compared with 7 months for patients who were FISH negative. (P =
      .04). Furthermore, survival favored FISH-positive patients receiving concurrent
      therapy. CONCLUSION: These results are the first to suggest that EGFR FISH is a
      predictive factor for selection of NSCLC patients for cetuximab plus
      chemotherapy. Prospective validation of these findings is warranted.

PMID- 18612152
TI  - Disclosure of incurable illness to spouses: do they want to know? A Swedish
      population-based follow-up study.
AB  - PURPOSE: Awareness of the cancer patient's terminal state decreases the risk of
      psychological morbidity of the bereaved. We wanted to determine whether male
      spouses of cancer patients who died from their disease had received information
      that the illness was incurable and to determine their preferences of disclosure.
      PARTICIPANTS AND METHODS: The study included 907 widowers whose wives had died of
      cancer. In an anonymous questionnaire, we asked whether the widower had received
      information that his wife's illness was incurable and about his attitudes towards
      receiving this information. RESULTS: Six hundred ninety-one widowers (76%)
      participated. Eighty percent of the widowers reported that they were told
      [corrected] that the wife's cancer was incurable, and 21% reported that they had
      been informed within 1 week before the patient's death. Although 14% of the
      widowers did not think the next of kin should be told immediately when the
      patient's cancer is beyond cure, 39% of the men did not want the patient to be
      immediately informed. Furthermore, 71% of the men who were never informed about
      the incurable illness believed that the next of kin should receive that
      information immediately. CONCLUSION: Although a large majority of men prefer an
      immediate disclosure about the incurable stage of their wife's illness, 41% of
      the husbands received this information during the last week of the patient's life
      or not at all. These findings indicate that there is room for improvement in the
      level of communication between health providers and the husbands of women with
      incurable cancer.

PMID- 18612153
TI  - Analysis of Maryland cancer patient participation in national cancer institute
      supported cancer treatment clinical trials.
AB  - PURPOSE: We examined the relationship of sociodemographic factors, urban/rural
      residence, and county-level socioeconomic factors on accrual of Maryland patients
      with cancer to National Cancer Institute (NCI) -sponsored cancer treatment
      clinical trials. PATIENTS AND METHODS: Data were analyzed for the period 1999 to
      2002 for 2,240 Maryland patients with cancer accrued onto NCI-sponsored treatment
      trials. The extent to which Maryland patients with cancer and patients residing
      in lower socioeconomic and/or rural areas were accrued to cancer trials and were
      representative of all patients with cancer in Maryland was determined. Data were
      obtained from several sources, including NCI's Cancer Therapy Evaluation Program
      for Maryland patients with cancer in Cooperative Group therapeutic trials,
      Maryland Cancer Registry data on cancer incidence, and United States Census and
      the Department of Agriculture. RESULTS: For Maryland patients with cancer accrued
      onto NCI-sponsored treatment trials between 1999 and 2002, subgroups accrued at a
      higher rate included pediatric and adolescent age groups, white patients, female
      patients (for sex-specific tumors), patients with private health insurance, and
      patients residing in the Maryland National Capitol region. Moreover, between 1999
      and 2002, there was an estimated annual decline (8.9% per year; P < .05) in the
      percentage of black patients accrued onto cancer treatment trials. Logistic
      regression models uncovered different patterns of accrual for female patients and
      male patients on county-level socioeconomic factors. CONCLUSION: Results
      highlight disparities in the accrual of Maryland patients with cancer onto NCI
      sponsored treatment trials based on patient age, race/ethnicity, geography of
      residence, and county-level socioeconomic factors. Findings provide the basis for
      development of innovative tailored and targeted educational efforts to improve
      trial accrual, particularly for the underserved.

PMID- 18612154
TI  - Obesity and risk of cancer in postmenopausal Korean women.
AB  - PURPOSE: To evaluate an association between obesity, measured by body mass index
      (BMI; kg/m(2)), and risk of cancer at individual and all sites in postmenopausal
      women. METHODS: A cohort of 170,481 postmenopausal Korean women who were age 40
      to 64 years at baseline measurement of BMI was observed prospectively from 1994
      to 2003 for cancer incidence. Multivariable adjusted proportional hazard models
      were used for evaluating the association. RESULTS: Women with a BMI of 30 kg/m(2)
      or higher had a 23% higher risk of cancer than women with a BMI between 21.0 and
      22.9 kg/m(2) (hazard ratio = 1.23; 95% CI, 1.08 to 1.41). According to the
      increase in BMI level, significant positive trends existed in cancers of colon,
      breast, corpus uteri, and kidney with hazard ratios of 1.05 (95% CI, 1.02 to
      1.08), 1.07 (95% CI, 1.05 to 1.10), 1.13 (95% CI, 1.07 to 1.20), and 1.08 (95%
      CI, 1.02 to 1.15), respectively, for the increase of BMI by 1 kg/m(2). When the
      analysis was limited to never-smokers, women with a BMI of 25 kg/m(2) or higher
      showed a significantly increased risk of cancers of the colon, breast, corpus
      uteri, and kidney and leukemia compared with the normal BMI (18.5 to 22.9
      kg/m(2)) group. CONCLUSION: Although variations exist between the individual
      cancer sites, obesity was associated with an overall increased risk of cancer in
      postmenopausal Korean women. To reduce the risk of cancer, active strategies to
      prevent obesity should be implemented in postmenopausal women.

PMID- 18612155
TI  - Activity of sunitinib in patients with advanced neuroendocrine tumors.
AB  - PURPOSE: Standard cytotoxic chemotherapy has limited efficacy in metastatic
      neuroendocrine tumor patients. Neuroendocrine tumors express vascular endothelial
      growth factor (VEGF) and its receptor (VEGFR). Sunitinib malate, an oral tyrosine
      kinase inhibitor, has activity against VEGFRs as well as platelet-derived growth
      factor receptors, stem-cell factor receptor, glial cell line-derived neurotrophic
      factor, and FMS-like tyrosine kinase-3. We evaluated the efficacy of sunitinib in
      a two-cohort, phase II study of advanced carcinoid and pancreatic neuroendocrine
      tumor patients. PATIENTS AND METHODS: Patients were treated with repeated 6-week
      cycles of oral sunitinib (50 mg/d for 4 weeks, followed by 2 weeks off
      treatment). Patients were observed for response, survival, and adverse events.
      Patient-reported outcomes were assessed. RESULTS: Among 109 enrolled patients,
      107 received sunitinib (carcinoid, n = 41; pancreatic endocrine tumor, n = 66).
      Overall objective response rate (ORR) in pancreatic endocrine tumor patients was
      16.7% (11 of 66 patients), and 68% (45 of 66 patients) had stable disease (SD).
      Among carcinoid patients, ORR was 2.4% (one of 41 patients), and 83% (34 of 41
      patients) had SD. Median time to tumor progression was 7.7 months in pancreatic
      neuroendocrine tumor patients and 10.2 months in carcinoid patients. One-year
      survival rate was 81.1% in pancreatic neuroendocrine tumor patients and 83.4% in
      carcinoid patients. No significant differences from baseline in patient-reported
      quality of life or fatigue were observed during treatment. CONCLUSION: Sunitinib
      has antitumor activity in pancreatic neuroendocrine tumors; its activity against
      carcinoid tumors could not be definitively determined in this nonrandomized
      study. Randomized trials of sunitinib in patients with neuroendocrine tumors are
      warranted.

PMID- 18612156
TI  - Severe sequence-specific toxicity when capecitabine is given after Fluorouracil
      and leucovorin.
AB  - PURPOSE: Options for single-agent fluoropyrimidine adjuvant therapy after bowel
      cancer resection include intravenous fluorouracil with leucovorin (FU/LV) or oral
      capecitabine. These treatments have similar efficacy but differ in convenience
      and toxicity. We therefore wished to compare their overall acceptability to
      patients. PATIENTS AND METHODS: Patients scheduled for adjuvant single-agent
      fluoropyrimidine therapy were randomly assigned to receive once-weekly FU/LV (425
      mg/m(2) FU, 45 mg LV) for 6 weeks, followed by two 3-week cycles of capecitabine
      (1,250 mg/m(2) twice daily, days 1 through 14), or the same treatments but in
      reverse order. After 12 weeks, the patients were asked which treatment they
      preferred, and received the preferred treatment for an additional 12 weeks. The
      primary end point was patient preference. RESULTS: After 40 of the planned 74
      patients had been randomly assigned, real-time adverse event monitoring led to
      early trial closure because of excess sequence-specific toxicity. Eleven of 14
      patients (79%) receiving capecitabine as their second treatment experienced grade
      >/= 3 toxicity. This compared with five of 18 patients (28%) receiving
      capecitabine as the first treatment, and no patients receiving FU/LV as the first
      treatment (zero of 16) or the second treatment (zero of 12). Similar imbalances
      were seen in the proportion of patients requiring interruption of treatment.
      CONCLUSION: In chemotherapy-naive patients, capecitabine produced more toxicity
      than FU/LV, but at levels in line with previously reported data. However,
      treatment with capecitabine after FU/LV caused markedly increased toxicity,
      indicating a sequence-specific interaction. The mechanism has not been
      determined, but interaction with intracellularly retained folate after FU/LV
      therapy is a possibility. Oncologists need to be aware of this risk if
      considering crossing patients over from FU/LV to capecitabine-based regimens.

PMID- 18612157
TI  - Phase II evaluation of imatinib mesylate in the treatment of recurrent or
      persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic
      Oncology Group Study.
AB  - PURPOSE: This phase II trial assessed the activity and tolerability of an oral
      dose of imatinib mesylate 400 mg twice daily in patients with recurrent or
      persistent epithelial ovarian or primary peritoneal carcinoma. The association
      between the expression of certain markers and clinical outcome was investigated.
      PATIENTS AND METHODS: Primary measure of clinical efficacy was progression-free
      survival (PFS) at 6 months. Mutational analysis of KIT, immunohistochemistry
      (IHC) and enzyme-linked immunosorbent assay for markers (KIT, platelet-derived
      growth factor [PDGF] receptor [-R], AKT2, phosphorylated AKT [p-AKT], stem cell
      factor [SCF], and PDGF) were performed. RESULTS: Fifty-six eligible patients were
      evaluated. Nine patients were progression free for at least 6 months including
      one complete responder. The median PFS and survival were 2 and 16 months,
      respectively. The most common grade 3 and 4 toxicities were neutropenia, GI,
      dermatologic effects, pain, and electrolyte disturbances. At least one target of
      imatinib (KIT, PDGFR-alpha, or PDGFR-beta) was expressed in all tumors, and most
      tumors expressed all three receptors. Higher expression of p-AKT and PDGFR-beta
      were associated with shorter PFS, and higher IHC scores (% immunopositive cells x
      staining intensity) of SCF and p-AKT were associated with decreased overall
      survival. No sequence mutations were detected in the KIT gene. Higher
      pretreatment plasma concentrations of PDGF-AB, PDGF-BB, and vascular endothelial
      growth factor (VEGF) were individually associated with shorter PFS and survival.
      CONCLUSION: Imatinib mesylate was well tolerated but had minimal single-agent
      activity in patients with recurrent ovarian or primary peritoneal carcinoma. No
      marker was identified that would predict activity of imatinib; however, tumor p
      AKT and plasma VEGF levels were associated with poor outcome.

PMID- 18612158
TI  - Results of the first phase I clinical trial of the novel II-key hybrid preventive
      HER-2/neu peptide (AE37) vaccine.
AB  - PURPOSE: HER-2/neu is overexpressed in breast cancer and is the source of
      immunogenic peptides. CD4(+) T-helper peptides for HER-2/neu are being evaluated
      in vaccine trials. The addition of Ii-Key, a four-amino-acid LRMK modification,
      increases vaccine potency when compared with unmodified class II epitopes. We
      present the results of the first human phase I trial of the Ii-Key hybrid HER
      2/neu peptide (AE37) vaccine in disease-free, node-negative breast cancer
      patients. PATIENTS AND METHODS: The dose escalation trial included five dose
      groups, to determine safety and optimal dose of the hybrid peptide (100 microg,
      500 microg, 1,000 microg) and granulocyte-macrophage colony-stimulating factor
      (GM-CSF; range, 0 to 250 microg). In the event of significant local toxicity, GM
      CSF (or peptide in absence of GM-CSF) was reduced by 50%. Immunologic response
      was monitored by delayed-type hypersensitivity and [(3)H]thymidine proliferative
      assays for both the hybrid AE37 (LRMK-positive HER-2/neu:776-790) and AE36
      (unmodified HER-2/neu:776-790). RESULTS: All 15 patients completed the trial with
      no grade 3 to 5 toxicities. Dose reductions occurred in 47% of patients. In the
      second group (peptide, 500 microg; GM-CSF, 250 microg), all patients required
      dose reductions, prompting peptide-only inoculations in the third group. The
      vaccine induced dose-dependent immunologic responses in vitro and in vivo to
      AE37, as well as AE36. CONCLUSION: The hybrid AE37 vaccine seems safe and well
      tolerated with minimal toxicity if properly dosed. AE37 is capable of eliciting
      HER-2/neu-specific immune responses, even without the use of an adjuvant. This
      trial represents the first human experience with the Ii-Key modification, and to
      our knowledge, AE37 is the first peptide vaccine to show potency in the absence
      of an immunoadjuvant.

PMID- 18612159
TI  - Prevalence of adenomas and hyperplastic polyps in mismatch repair mutation
      carriers among CAPP2 participants: report by the colorectal adenoma/carcinoma
      prevention programme 2.
AB  - PURPOSE: To determine the prevalence of adenomatous and hyperplastic polyps in a
      large cohort of individuals with a germline mutation in a mismatch repair (MMR)
      gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer
      (HNPCC). These prevalences have been estimated previously in smaller studies, and
      the results have been found to be variable. PATIENTS AND METHODS: Colorectal
      Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in
      people classified as having HNPCC. The 695 patients with a proven germline MMR
      mutation and documented screening history before the chemoprevention study were
      the focus of this study. The number, histology, size, and location of polyps
      found at the participants' first ever colonoscopy were analyzed in a cross
      sectional study. RESULTS: Seventy-four patients (10.6%) were found to have at
      least one adenoma at first colonoscopy, whereas 37 (5.3%) had at least one
      hyperplastic polyp. The frequency of an adenoma at first colonoscopy increased
      from 5.0% (95% CI, 2.8% to 8.3%) in patients younger than 35 years old to 18.9%
      (95% CI, 9.4% to 32.0%) in patients age at least 55 years (P = .0001 for trend).
      No such trend was observed for hyperplastic polyps. No sex differences were found
      for either type of polyp. A marginal association was found between the co
      occurrence of adenomas and hyperplastic polyps. Adenomas tended to be more
      proximally distributed through the colon, whereas hyperplastic polyps tended to
      be located in the distal colon. CONCLUSION: Adenoma prevalence increases with age
      among MMR mutation carriers, whereas hyperplastic polyp prevalence is consistent.
      No sex differences were observed for either type of lesion.

PMID- 18612160
TI  - Impact of intensity-modulated radiation therapy on local control in primary soft
      tissue sarcoma of the extremity.
AB  - PURPOSE: One of the concerns about intensity-modulated radiation therapy (IMRT)
      is that its tight dose distribution, an advantage in reducing RT morbidity to
      surrounding normal structures, might compromise tumor coverage. The purpose of
      this study is to determine if such concern is warranted in soft-tissue sarcoma
      (STS) of the extremity. METHODS: Between 02/02 and 05/05, 41 adult patients with
      primary STS of the extremity were treated with limb-sparing surgery and adjuvant
      IMRT. The margins were positive/within 1 mm in 21. Tumor size was more than 10 cm
      in 68% of patients and grade was high in 83%. Preoperative IMRT was given to 7
      patients (50 Gy) and postoperative IMRT (median dose, 63 Gy) was given to 34
      patients. Complete gross resection including periosteal stripping/bone resection
      was required in 11, and neurolysis/nerve resection in 24. RESULTS: With a median
      follow-up time of 35 months, two (4.8%) of 41 patients developed local
      recurrence. The 5-year actuarial local control rate was 94% (95% CI, 86% to
      100%). The local control rate was also 94% for patients with negative or
      positive/close margin. Other prognostic factors such as age, size, and grade did
      not impact local control either. The 5-year distant control rate was 61% (95% CI,
      45% to 76%) and the overall survival rate was 64% (95% CI, 45% to 84%).
      CONCLUSION: IMRT in STS of the extremity provides excellent local control in a
      group of patients with high risk features. This suggests that the precision with
      which IMRT dose is distributed has a beneficiary effect in sparing normal tissue
      and improving local control.

PMID- 18612161
TI  - Next generation of immunotherapy for melanoma.
AB  - PURPOSE: Immunotherapy has a long history with striking but limited success in
      patients with melanoma. To date, interleukin-2 and interferon-alfa2b are the only
      approved immunotherapeutic agents for melanoma in the United States. DESIGN:
      Tumor evasion of host immune responses, and strategies for overcoming tumor
      induced immunosuppression are reviewed. Several novel immunotherapies currently
      in worldwide phase III clinical testing for melanoma are discussed. RESULTS: The
      limitations of immunotherapy for melanoma stem from tumor-induced mechanisms of
      immune evasion that render the host tolerant of tumor antigens. For example,
      melanoma inhibits the maturation of antigen-presenting cells, preventing full T
      cell activation and downregulating the effector antitumor immune response. New
      immunotherapies targeting critical regulatory elements of the immune system may
      overcome tolerance and promote a more effective antitumor immune response. These
      include monoclonal antibodies that block the cytotoxic T lymphocyte-associated
      antigen 4 (CTLA4) and toll-like receptor 9 (TLR9) agonists. Blockade of CTLA4
      prevents inhibitory signals that downregulate T-cell activation. TLR9 agonists
      stimulate dendritic cell maturation and ultimately induce a more effective immune
      response. These approaches have been shown to stimulate acute immune activation
      with concomitant appearance of transient adverse events mediated by the immune
      system. The pattern and duration of immune responses associated with these new
      modalities differ from those associated with cytokines and cytotoxic agents. In
      addition, vaccines are being developed that may ultimately target melanoma either
      alone or in combination with these immunomodulatory therapies. CONCLUSION: The
      successes of cytokine and interferon therapy of melanoma, coupled with an array
      of new approaches, are generating new enthusiasm for the immunotherapy of
      melanoma.

PMID- 18612162
TI  - Lung carcinoma associated with excessive eosinophilia.

PMID- 18612163
TI  - Sirolimus in metatastic renal cell carcinoma.

PMID- 18612164
TI  - Trichomegaly of the eyelashes after lung cancer treatment with the epidermal
      growth factor receptor inhibitor erlotinib.

PMID- 18612165
TI  - Folate in head and neck squamous cell cancer chemoprevention: purposely left out?

PMID- 18612166
TI  - Opioid-induced pain.

PMID- 18612167
TI  - Breast magnetic resonance imaging in early-stage breast cancer: is there really
      no value?

PMID- 18612168
TI  - Methylenetetrahydrofolate reductase gene polymorphisms: genomic predictors of
      clinical response to fluoropyrimidine-based chemotherapy in females.

PMID- 18612169
TI  - Efficacy of sunitinib and sorafenib in non-clear cell renal cell carcinoma:
      results from expanded access studies.

PMID- 18612170
TI  - Cotyledon organogenesis.
AB  - The cotyledon represents one of the bases of classification within the plant
      kingdom, providing the name-giving difference between dicotyledonous and
      monocotyledonous plants. It is also a fundamental organ and there have been many
      reports of cotyledon mutants in many species. The use of these mutants where they
      have arisen in Arabidopsis has allowed us to unravel some of the complexities of
      embryonic patterning and cotyledon development with a high degree of resolution.
      The cloning of genes involved in cotyledon development from other species,
      together with physiological work, has supported the hypothesis that there exists
      a small number of orthologous gene hierarchies, particularly those involving
      auxin. The time is therefore appropriate for a summary of the regulation of
      cotyledon development gleaned from cotyledon mutants and regulatory pathways in
      the model species Arabidopsis and what can be inferred from cotyledon mutants in
      other species. There is an enormous variation in cotyledon form and development
      throughout the plant kingdom and this review focuses on debates about the
      phylogenetic relationship between mono- and dicotyledony, discusses gymnosperm
      cotyledon development and pleiocotyly in natural populations, and explores the
      limits of homology between cotyledons and leaves.

PMID- 18612171
TI  - Anion channel activity is necessary to induce ethylene synthesis and programmed
      cell death in response to oxalic acid.
AB  - Oxalic acid is thought to be a key factor of the early pathogenicity stage in a
      wide range of necrotrophic fungi. Studies were conducted to determine whether
      oxalate could induce programmed cell death (PCD) in Arabidopsis thaliana
      suspension cells and to detail the transduction of the signalling pathway induced
      by oxalate. Arabidopsis thaliana cells were treated with millimolar
      concentrations of oxalate. Cell death was quantified and ion flux variations were
      analysed from electrophysiological measurements. Involvement of the anion channel
      and ethylene in the signal transduction leading to PCD was determined by using
      specific inhibitors. Oxalic acid induced a PCD displaying cell shrinkage and
      fragmentation of DNA into internucleosomal fragments with a requirement for
      active gene expression and de novo protein synthesis, characteristic hallmarks of
      PCD. Other responses generally associated with plant cell death, such as anion
      effluxes leading to plasma membrane depolarization, mitochondrial depolarization,
      and ethylene synthesis, were also observed following addition of oxalate. The
      results show that oxalic acid activates an early anionic efflux which is a
      necessary prerequisite for the synthesis of ethylene and for the PCD in A.
      thaliana cells.

PMID- 18612172
TI  - Optimization of light source parameters in the photodynamic therapy of
      heterogeneous prostate.
AB  - The three-dimensional (3D) heterogeneous distributions of optical properties in a
      patient prostate can now be measured in vivo. Such data can be used to obtain a
      more accurate light-fluence kernel. (For specified sources and points, the kernel
      gives the fluence delivered to a point by a source of unit strength.) In turn,
      the kernel can be used to solve the inverse problem that determines the source
      strengths needed to deliver a prescribed photodynamic therapy (PDT) dose (or
      light-fluence) distribution within the prostate (assuming uniform drug
      concentration). We have developed and tested computational procedures to use the
      new heterogeneous data to optimize delivered light-fluence. New problems arise,
      however, in quickly obtaining an accurate kernel following the insertion of
      interstitial light sources and data acquisition. (1) The light-fluence kernel
      must be calculated in 3D and separately for each light source, which increases
      kernel size. (2) An accurate kernel for light scattering in a heterogeneous
      medium requires ray tracing and volume partitioning, thus significant calculation
      time. To address these problems, two different kernels were examined and compared
      for speed of creation and accuracy of dose. Kernels derived more quickly involve
      simpler algorithms. Our goal is to achieve optimal dose planning with patient
      specific heterogeneous optical data applied through accurate kernels, all within
      clinical times. The optimization process is restricted to accepting the given
      (interstitially inserted) sources, and determining the best source strengths with
      which to obtain a prescribed dose. The Cimmino feasibility algorithm is used for
      this purpose. The dose distribution and source weights obtained for each kernel
      are analyzed. In clinical use, optimization will also be performed prior to
      source insertion to obtain initial source positions, source lengths and source
      weights, but with the assumption of homogeneous optical properties. For this
      reason, we compare the results from heterogeneous optical data with those
      obtained from average homogeneous optical properties. The optimized treatment
      plans are also compared with the reference clinical plan, defined as the plan
      with sources of equal strength, distributed regularly in space, which delivers a
      mean value of prescribed fluence at detector locations within the treatment
      region. The study suggests that comprehensive optimization of source parameters
      (i.e. strengths, lengths and locations) is feasible, thus allowing acceptable
      dose coverage in a heterogeneous prostate PDT within the time constraints of the
      PDT procedure.

PMID- 18612173
TI  - HDRK-Man: a whole-body voxel model based on high-resolution color slice images of
      a Korean adult male cadaver.
AB  - A Korean voxel model, named 'High-Definition Reference Korean-Man (HDRK-Man)',
      was constructed using high-resolution color photographic images that were
      obtained by serially sectioning the cadaver of a 33-year-old Korean adult male.
      The body height and weight, the skeletal mass and the dimensions of the
      individual organs and tissues were adjusted to the reference Korean data. The
      resulting model was then implemented into a Monte Carlo particle transport code,
      MCNPX, to calculate the dose conversion coefficients for the internal organs and
      tissues. The calculated values, overall, were reasonable in comparison with the
      values from other adult voxel models. HDRK-Man showed higher dose conversion
      coefficients than other models, due to the facts that HDRK-Man has a smaller
      torso and that the arms of HDRK-Man are shifted backward. The developed model is
      believed to adequately represent average Korean radiation workers and thus can be
      used for more accurate calculation of dose conversion coefficients for Korean
      radiation workers in the future.

PMID- 18612174
TI  - Radiation dose and image quality for paediatric interventional cardiology.
AB  - Radiation dose and image quality for paediatric protocols in a biplane x-ray
      system used for interventional cardiology have been evaluated. Entrance surface
      air kerma (ESAK) and image quality using a test object and polymethyl
      methacrylate (PMMA) phantoms have been measured for the typical paediatric
      patient thicknesses (4-20 cm of PMMA). Images from fluoroscopy (low, medium and
      high) and cine modes have been archived in digital imaging and communications in
      medicine (DICOM) format. Signal-to-noise ratio (SNR), figure of merit (FOM),
      contrast (CO), contrast-to-noise ratio (CNR) and high contrast spatial resolution
      (HCSR) have been computed from the images. Data on dose transferred to the DICOM
      header have been used to test the values of the dosimetric display at the
      interventional reference point. ESAK for fluoroscopy modes ranges from 0.15 to
      36.60 microGy/frame when moving from 4 to 20 cm PMMA. For cine, these values
      range from 2.80 to 161.10 microGy/frame. SNR, FOM, CO, CNR and HCSR are improved
      for high fluoroscopy and cine modes and maintained roughly constant for the
      different thicknesses. Cumulative dose at the interventional reference point
      resulted 25-45% higher than the skin dose for the vertical C-arm (depending of
      the phantom thickness). ESAK and numerical image quality parameters allow the
      verification of the proper setting of the x-ray system. Knowing the increases in
      dose per frame when increasing phantom thicknesses together with the image
      quality parameters will help cardiologists in the good management of patient dose
      and allow them to select the best imaging acquisition mode during clinical
      procedures.

PMID- 18612175
TI  - Experimental feasibility of multi-energy photon-counting K-edge imaging in pre
      clinical computed tomography.
AB  - Theoretical considerations predicted the feasibility of K-edge x-ray computed
      tomography (CT) imaging using energy discriminating detectors with more than two
      energy bins. This technique enables material-specific imaging in CT, which in
      combination with high-Z element based contrast agents, opens up possibilities for
      new medical applications. In this paper, we present a CT system with energy
      detection capabilities, which was used to demonstrate the feasibility of
      quantitative K-edge CT imaging experimentally. A phantom was imaged containing
      PMMA, calcium-hydroxyapatite, water and two contrast agents based on iodine and
      gadolinium, respectively. Separate images of the attenuation by photoelectric
      absorption and Compton scattering were reconstructed from energy-resolved
      projection data using maximum-likelihood basis-component decomposition. The data
      analysis further enabled the display of images of the individual contrast agents
      and their concentrations, separated from the anatomical background. Measured
      concentrations of iodine and gadolinium were in good agreement with the actual
      concentrations. Prior to the tomographic measurements, the detector response
      functions for monochromatic illumination using synchrotron radiation were
      determined in the energy range 25 keV-60 keV. These data were used to calibrate
      the detector and derive a phenomenological model for the detector response and
      the energy bin sensitivities.

PMID- 18612176
TI  - Quantitative sonoelastography for the in vivo assessment of skeletal muscle
      viscoelasticity.
AB  - A novel quantitative sonoelastography technique for assessing the viscoelastic
      properties of skeletal muscle tissue was developed. Slowly propagating shear wave
      interference patterns (termed crawling waves) were generated using a two-source
      configuration vibrating normal to the surface. Theoretical models predict
      crawling wave displacement fields, which were validated through phantom studies.
      In experiments, a viscoelastic model was fit to dispersive shear wave speed
      sonoelastographic data using nonlinear least-squares techniques to determine
      frequency-independent shear modulus and viscosity estimates. Shear modulus
      estimates derived using the viscoelastic model were in agreement with that
      obtained by mechanical testing on phantom samples. Preliminary sonoelastographic
      data acquired in healthy human skeletal muscles confirm that high-quality
      quantitative elasticity data can be acquired in vivo. Studies on relaxed muscle
      indicate discernible differences in both shear modulus and viscosity estimates
      between different skeletal muscle groups. Investigations into the dynamic
      viscoelastic properties of (healthy) human skeletal muscles revealed that
      voluntarily contracted muscles exhibit considerable increases in both shear
      modulus and viscosity estimates as compared to the relaxed state. Overall,
      preliminary results are encouraging and quantitative sonoelastography may prove
      clinically feasible for in vivo characterization of the dynamic viscoelastic
      properties of human skeletal muscle.

PMID- 18612177
TI  - Target-tracking deliveries using conventional multileaf collimators planned with
      4D direct-aperture optimization.
AB  - Respiratory motion-induced degradation of intensity-modulated radiotherapy can be
      corrected by the dynamic target-tracking motion of multileaf collimator equipment
      on a conventional linear accelerator. This paper presents a new system by which
      the motion of the tissue and the delivery equipment can be incorporated into the
      treatment optimization using a 4D direct-aperture optimization method. The
      program can optimize a static or dynamic delivery with respect to a 4D patient
      model. The individualized patient model consists of a series of discrete phases
      and describes changes in tissue: deformation, geometry, attenuation and scatter
      properties over the breathing cycle. A set of treatment apertures is matched to
      the respiratory phases of the motion model, and motion of the apertures between
      phases is constrained by the maximum leaf velocity. Plans with dynamic and static
      deliveries optimized on 4D patient models were compared to static plans optimized
      on a single phase. This investigation was carried out on a 4D digital motion
      phantom and repeated on a 4D patient model. The effect of motion of the static
      plan on the 4D phantom was evaluated by recalculating dose from all phases of the
      4D model. The plan cost was evaluated as a combination of the rms spread in
      tumour dose from the prescribed dose and the volume of normal lung receiving
      doses above 10 Gy with relative weightings of 5 and 1 respectively. The motion
      was found to degrade the static plan by 30 +/- 4% with respect to the 3D cost
      function value. In contrast, the motion did not cause significant degradation to
      a treatment if the treatment was optimized on the 4D phantom and the cost was
      improved by 16 +/- 3% by optimizing with dynamic leaf tracking motion. All
      results are relative to the static single-phase plan. In the 4D patient model the
      observed tissue motion was considerably less and the measured benefit of 4D
      planning was consequently reduced. For the 4D patient the plan cost was not
      significantly changed by the tissue motion. Optimizing on 4D patient conferred an
      improvement of 7.5 +/- 0.3%, and the 4D plan with dynamic leaf motion improved
      the plan cost by 8.3 +/- 0.1%.

PMID- 18612178
TI  - Joint laminate degradation assessed by reflected ultrasound from the cartilage
      surface and osteochondral junction.
AB  - The ability to quantify and qualify the progression of joint degeneration is
      becoming increasingly important in surgery. This paper examines the patterns of
      relative ultrasound reflection from normal, artificially and naturally degraded
      cartilage-on-bone, particularly investigating the potential of the ratio of
      reflection coefficients from the surface and osteochondral junction in
      distinguishing normal from osteoarthritic tissue. To this end, the reflection
      coefficients from the articular surface and osteochondral junction of normal
      cartilage-on-bone samples were calculated and compared to samples after the
      removal of proteoglycans, disruption of the collagen meshwork, delipidization of
      the articular surface and mechanical abrasion. Our results show that the large
      variation across normal and degraded joint samples negates the use of an isolated
      bone reflection measurement and to a lesser extent, an isolated surface
      reflection. The relative surface to bone reflections, calculated as a ratio of
      reflection coefficients, provided a more consistent and statistically significant
      (p < 0.001) method for distinguishing each type of degradation, especially
      osteoarthritic degradation, and due to the complementary relationship between
      surface and bone reflections was found to be an effective method for
      distinguishing degraded from normal tissue in the osteoarthritic joint,
      independent of the site of initiation of the osteoarthritic process.

PMID- 18612179
TI  - Diagnostic accuracy of ultrasound features in thyroid microcarcinomas.
AB  - OBJECTIVE: To establish the usefulness of specific ultrasound (US) features as
      indications for ultrasound-guided fine needle aspiration biopsy (FNAB) in
      incidentally found infracentimetric thyroid nodules. METHODS: The
      ultrasonographic features and cytology of FNAB samples of 96 histopathologically
      proven papillary microcarcinomas (less than 1 cm in long diameter) and 75 less
      than 1 cm sized benign nodules were analyzed and compared. The risk of malignancy
      indicated by each US feature was calculated by logistic regression analysis.
      RESULTS: Among the US features examined, internal content, shape, margin,
      echogenicity, and calcifications showed statistically significant differences
      between benign and malignant infracentimetric nodules. Crude odds ratios (OR) and
      95% confidence intervals (CI) for risk of malignancy were, for solid content, OR
      = 39.3 (95% CI = 3.3-4.64); for taller than wide shape, OR = 14.2 (95% CI = 1.43
      14.1); for hypoechogenicity, OR = 3.57 (95% CI = 1.31-9.86); for marked
      hypoechogenicity, OR = 31.33 (95% CI = 6.63-14.8); and for coarse
      macrocalcifications, OR = 3.43 (95% CI = 1.04-11.3). CONCLUSIONS:
      Infracentimetric nodules that are solid, taller than wide, hypoechogenic or
      markedly hypoechogenic, and have coarse microcalcifications and
      macrocalcifications have a high risk of malignancy, indicating further
      assessment.

PMID- 18612180
TI  - Prognosis of patients with papillary carcinoma showing anaplastic transformation
      in regional lymph nodes that were curatively resected.
AB  - Anaplastic carcinoma arises from differentiated carcinoma and generally shows a
      dire prognosis. Anaplastic transformation may occur not only in primary tumors
      but also in metastatic lymph nodes. We encountered 5 cases of papillary carcinoma
      showing anaplastic transformation in lymph nodes that were curatively resected.
      Patient ages ranged from 67 to 85 years. Two of these patients showed anaplastic
      transformation at the initial surgery and the remaining 3 showed anaplastic
      transformation after repeated recurrence to the lymph nodes. After resection of
      anaplastic lesions of the nodes, 2 patients underwent radiation therapy, whereas
      the remaining 3 did not receive any adjuvant therapy. One patient died of rapid
      growth of lung metastasis 5 months after the resection. One patient died of
      carcinoma 63 months after surgery. Two patients have survived to date, 6 and 85
      months after resection, respectively. The remaining one patient died of heart
      failure 11 months after surgery. It is therefore suggested that long-term
      survival can be expected for patients with differentiated carcinoma showing
      anaplastic transformation in the lymph node if the lesions can be curatively
      resected.

PMID- 18612181
TI  - Metabolic co-morbidities revealed in patients with childhood-onset adult GH
      deficiency after cessation of GH replacement therapy for short stature.
AB  - GH therapy was approved in 2006 for treatment of adult growth hormone deficiency
      (GHD) in Japan. Until then, GH was used only to treat short stature in children
      with GHD and the treatment was stopped when the final height was reached. In the
      present study, we investigated metabolic co-morbidities experienced by adults
      with childhood-onset (CO) GHD after the cessation of GH. Forty-two patients with
      COGHD (M/F 22/20, age at follow up when the retrospective analysis was carried
      out: 18-52 yr) treated with GH in childhood were studied. We reviewed the medical
      records of these patients to determine the metabolic co-morbidities that
      developed after cessation of GH. The median age was 19 yrs (range: 14-38) at
      cessation of GH, and the following co-morbidities were observed:
      hypertriglyceridemia in 15 (41%) patients, non-alcoholic fatty liver disease
      (NAFLD) in 11 (29%) patients, hypercholesterolemia in 10 (26%) patients, diabetes
      mellitus (DM) in 4 (10%) patients, and hypertension in 1 (2.4%) patient. The
      median BMI when these complications became overt was 23.5 kg/m(2) for those with
      hypertriglyceridemia, 26.0 kg/m(2) for those with NAFLD, 20.9 kg/m(2) for those
      with hypercholesterolemia, and 27.2 kg/m(2 ) for those with DM. More than two co
      morbidities were experienced by 32% of men and 30% of women. In conclusion,
      adults with COGHD after the cessation of GH have multiple metabolic co
      morbidities. Lifelong GH replacement might be important for improving the overall
      metabolic profiles in these patients.

PMID- 18612182
TI  - Distribution of blood glucose and the correlation between blood glucose and
      hemoglobin A1c levels in diabetic outpatients.
AB  - PURPOSE OF THE STUDY: Tight glycemic control is important for the prevention of
      microvascular complications in diabetic patients. We examined the reliability of
      using blood glucose levels measured at various time-points relative to a meal as
      an index of glycemic control in Japanese diabetic outpatients. Basic procedures
      followed: We examined the correlation between the fasting blood glucose (FBG)
      level; the one-hour (1-h), two-hour (2-h), and three-hour (3-h) post breakfast
      blood glucose (PBBG) levels, the 1 h, 2 h, and 3 h post lunch blood glucose
      (PLBG) levels and the hemoglobin A1c (HbA1c) levels in Japanese diabetic
      outpatients. A total of 11451 patient-visits to the Marunouchi Hospital between
      January 2002 and December 2002 were included in the study. The main findings: The
      blood glucose levels measured at all of the above time-points were significantly
      correlated with the HbA1c level. As calculated using local polynomial regression
      fitting, the FPG, 1-h, 2-h, and 3-h PBBG levels that corresponded to an HbA1c
      level of 6.5% were 132 mg/dL, 174 mg/dL, 170 mg/dL, and 143 mg/dL, respectively.
      The FPG and 2-h PBBG levels exhibited a good sensitivity and specificity for
      predicting a glycemic control corresponding to an HbA1c<5.8%, while the FPG and 3
      h PBBG levels exhibited fair sensitivity and specificity for predicting glycemic
      control corresponding to an HbA1c<6.5%. The principal conclusions: The FBG, 2
      hPBBG, and 3-hPBBG levels can be used as rough estimates of glycemic control in
      Japanese diabetic outpatients.

PMID- 18612183
TI  - Effect of hospital case volume on treatment and in-hospital outcomes in patients
      undergoing percutaneous coronary intervention for acute myocardial infarction.
      Results from the Ibaraki Coronary Artery Disease Study (ICAS) Registry.
AB  - The volume of percutaneous coronary interventions (PCI) performed in a hospital
      has been suggested to correlate with favorable outcomes in patients undergoing
      primary PCI for acute myocardial infarction (AMI). However, studies that use
      current data and compare treatment and outcomes for AMI among hospitals with
      different volumes are still limited in Japan. Between January 2004 and March
      2006, 401 AMI patients underwent primary PCI in the 11 hospitals participating in
      the Ibaraki Coronary Artery Disease Study (ICAS). Clinical characteristics,
      treatment, and in-hospital outcomes were retrospectively compared between 254
      patients admitted to high-volume PCI hospitals and 147 patients admitted to low
      volume hospitals. Low-volume hospitals had a higher prevalence of multivessel
      disease patients. High-volume hospitals had longer onset-to-door times, which
      were offset by faster door-to-balloon times. Rates of coronary stent use and
      successful PCI were comparable between the groups. Low-volume hospitals more
      frequently performed intra-aortic balloon pumping. Length of stay was longer in
      low-volume hospitals, whereas in-hospital mortality, bypass surgery, and repeat
      PCI rates did not differ between groups. Although the present study assessed
      limited data based on small sample size, we observed that contemporary standard
      treatments including stent implantation were performed for AMI patients
      undergoing primary PCI in hospitals with both high and low case volumes. We did
      not find an obvious relationship between hospital PCI volume and in-hospital
      outcomes in our data. However, further prospective surveys should be attempted to
      confirm these results.

PMID- 18612184
TI  - Cigarette smoking augments sympathetic nerve activity in patients with coronary
      heart disease.
AB  - It has been shown that cigarette smoking increases blood pressure (BP) and heart
      rate (HR), and decreases muscle sympathetic nerve activity (MSNA) in healthy
      young smokers. The decrease in MSNA might be secondary to baroreflex responses to
      the pressor effect. We tested the hypothesis that cigarette smoking increases
      MSNA in smokers with impaired baroreflex function. The effects of cigarette
      smoking on BP, HR, forearm blood flow (FBF), forearm vascular resistance (FVR),
      and MSNA were examined in 14 patients with stable effort angina (59+/-3 years,
      group CAD) and 10 healthy smokers (23+/-1 years, group C). In group CAD, the
      arterial baroreflex sensitivity (BRS) was significantly lower than in group C
      (4.7+/-0.8 versus 15.1+/-2.2 msec/mmHg, P<0.01). In both groups, cigarette
      smoking increased the plasma concentration of nicotine, systolic and diastolic
      BP, HR, and FVR significantly (P<0.01), but decreased FBF significantly (P<0.01).
      After smoking, MSNA was decreased significantly in group C (from 35.2+/-3.5 to
      23.5+/-3.2 bursts/100 beats, P<0.01), but increased significantly in group CAD
      (from 48.8+/-5.4 to 57.3+/-5.5 bursts/100 beats, P<0.01). There was significant
      correlation between BRS and changes in MSNA (r= -0.62, P<0.01). Cigarette smoking
      increased MSNA in smokers with impaired baroreflex function. This demonstrates
      that cigarette smoking stimulates sympathetic nerve activity by both a direct
      peripheral effect and a centrally mediated effect.

PMID- 18612185
TI  - Efficacy of consistent atrial pacing algorithm for suppression of atrial
      arrhythmias in patients with sick sinus syndrome and atrial fibrillation.
AB  - Atrial overdrive provides the best opportunity to suppress atrial arrhythmias.
      Atrial preference pacing (APP) algorithm has been designed to achieve a high
      percentage of atrial pacing. The aim of this study was to assess the efficacy of
      APP algorithm in patients with implanted pacemakers and tachycardia-bradycardia
      syndrome. The subjects were 17 patients (mean age, 71.7+/-9.0 years old, 4 males)
      implanted with a DDDR pacemaker Thera DR (Medtronic, Minneapolis, MN, USA). All
      patients had sick sinus syndrome and paroxysmal atrial fibrillation before
      pacemaker implantation. Informed consent was obtained from each participant
      before enrollment. DDDR and mode switch or APP were randomly programmed. After
      two weeks, the pacing mode was switched to another mode. The percentage of atrial
      pacing was significantly higher in APP than in DDDR (97.7+/-1.4 versus 52.3+/
      30.8, P<0.0001). Atrial premature beat counts were significantly greater in DDDR
      than in APP (30689+/-42534 versus 7717+/-10700, P<0.005). There was no
      significant difference in mode switch episode counts between DDIR and APP (2.6+/
      5.5 versus 8.4+/-19.2, NS). Although there was no significant difference in mode
      switch episode counts between DDDR and APP, APP algorithm can successfully
      prevent atrial premature beats in patients with tachycardia-bradycardia syndrome.

PMID- 18612186
TI  - Antiarrhythmic effect of bisoprolol, a highly selective beta1-blocker, in
      patients with paroxysmal atrial fibrillation.
AB  - In the treatment of arrhythmia, beta-blockers are mainly used to regulate the
      heart rate. However, beta-blockers are also known as drugs with an antiarrhythmic
      effect due to the suppression of sympathetic activity. We evaluated the
      antiarrhythmic effects of a highly selective beta(1)-blocker, bisoprolol, in
      patients with diurnal paroxysmal atrial fibrillation (P-AF). A total of 136
      patients with symptomatic diurnal P-AF were enrolled. Patients were divided into
      a diurnal-specific P-AF group and a diurnal & nocturnal P-AF group, as well as
      into a bisoprolol single use group and a combined use group with an
      antiarrhythmic drug. The effects of bisoprolol were evaluated in 3 categories:
      subjective symptom improvement, quality of life (QOL) improvement, and
      elimination of P-AF episode in Holter electrocardiograms (ECGs). For patients
      with effective treatment, a long-term effect up to 24 months was evaluated. Five
      patients (3.7%) discontinued bisoprolol due to side effects. Following
      administration of bisoprolol, 109 patients (80%) experienced subjective symptom
      improvement, 103 patients (76%) experienced QOL improvement, and elimination of P
      AF episodes in ECGs was observed in 84 patients (62%). The elimination rate of P
      AF episodes in ECGs was higher in the diurnal P-AF group than in the diurnal &
      nocturnal P-AF group (P=0.042). There was no significant difference between the
      bisoprolol single use group and the combined use group. A long-term suppressive
      effect by bisoprolol was observed in 70 of 83 patients (84%). The results
      demonstrate that bisoprolol has an antiarrhythmic effect against sympathetic
      diurnal P-AF, improving subjective symptoms and QOL and eliminating P-AF episodes
      in ECGs.

PMID- 18612187
TI  - Significance of pulsatility of brachial artery pressure for blood pressure
      control.
AB  - Few studies have examined predictors of poor blood pressure (BP) control. The aim
      of this study was to observe the relationship between the pulsatility of brachial
      artery pressure characterized as pulse pressure/diastolic pressure (PP/DP),
      suggesting aortic input impedance, and poor BP control. We obtained office BP
      measurements for 94 patients aged 40-75 years with either office systolic BP
      (SBP) >or= 140 mmHg or diastolic BP (DBP) >or= 90 mmHg. Patients were given a
      single antihypertensive agent or were untreated at baseline. The angiotensin II
      receptor blocker valsartan (80 mg) was administered to all patients. Patients
      were treated with 1 to 2 antihypertensive drugs (valsartan only or valsartan + Ca
      antagonist) for 6 months to achieve an office BP of less than 140/90 mmHg. At
      follow-up, 32 patients were taking a single drug (valsartan) with good BP
      control, 24 were receiving two drugs with good BP control, and 38 were on two
      drugs with poor BP control. SBP and DBP at baseline were similar in the 3 groups.
      PP/DP at baseline differed in the 3 groups (P<0.01). In multivariate analysis,
      only PP/DP at baseline correlated with lack of BP control. The pulsatility of
      brachial artery pressure is associated with achieving adequate BP control.

PMID- 18612188
TI  - Short term fluvastatin treatment lowers serum asymmetric dimethylarginine levels
      in patients with metabolic syndrome.
AB  - Elevated concentrations of asymmetric dimethylarginine (ADMA), an endogenous
      inhibitor of nitric oxide synthase, are associated with endothelial dysfunction.
      Metabolic syndrome (MetS) is also a condition associated with impaired
      endothelial function. To test the hypothesis that lipid lowering treatment with a
      statin lowers ADMA levels, we investigated the effect of fluvastatin treatment on
      serum ADMA levels in patients with MetS. A total of 85 hypercholesterolemic MetS
      patients (53 females, 32 males; mean age, 55.8+/-9.1 years) were included in this
      prospective, randomized, controlled study. Patients were randomly assigned to
      either the treatment (n=42) or control group (n=43). Recommendations for
      lifestyle modification were provided to both groups. In addition, the patients in
      the treatment group received fluvastatin, extended release tablets, 80 mg/day,
      orally for 6 weeks. Serum levels of ADMA and lipids were assessed at baseline and
      at the completion of treatment. High performance liquid chromatography was used
      to measure serum ADMA concentrations. In the fluvastatin group, there was a
      significant reduction in serum ADMA levels compared to baseline (from 1.57+/-1.07
      micromol/L to 1.17+/-1.41 micromol/L, P<0.05), whereas in the control group no
      significant change was observed (from 1.06+/-0.46 micromol/L to 1.24+/-1.38
      micromol/L, P>0.05). There was a statistically significant difference between the
      groups in terms of mean percent change from baseline (P=0.047). Fluvastatin
      treatment for hypercholesterolemia in patients with MetS is associated with a
      decrease in serum ADMA levels at 6 weeks. This finding is consistent with known
      beneficial effects of statin treatment on endothelial function in
      hypercholesterolemic patients.

PMID- 18612189
TI  - Genetic variations of Mrf-2/ARID5B confer risk of coronary atherosclerosis in the
      Japanese population.
AB  - A phenotypic change of smooth muscle cells (SMCs) is considered to be critical in
      the pathogenesis of atherosclerotic lesions such as coronary artery disease
      (CAD). Mrf-2/ARID5B, a member of the AT-rich interaction domain family of
      transcription factors, is highly expressed in the cardiovascular system and is
      believed to play essential roles in the phenotypic change of SMCs through its
      regulation of SMC differentiation. In addition, recent studies on gene-engineered
      mice suggested that this transcriptional factor is involved in obesity and
      adipogenesis, which are critical aspects for the pathogenesis of atherosclerosis.
      Thus, we hypothesized that genetic variations of the Mrf-2 gene might be
      associated with susceptibility to CAD. We investigated 11 common genetic
      variations of Mrf-2 to determine whether they were associated with susceptibility
      to CAD in 475 CAD subjects and 310 control subjects. The prevalence of
      homozygotes for the minor allele G of SNP4 (rs2893880) and minor allele G of SNP6
      (rs7087507) were significantly more frequent in the control subjects than in
      patients with CAD (P=0.0002, rs2893880, P=0.0058, rs7087507). Four nearby SNPs
      (SNP4 to SNP7) (rs2893880, rs10740055, rs7087507 and rs10761600) showed almost
      complete linkage disequilibrium, and haplotype analysis revealed that the
      haplotype G (rs2893880)-C (rs10740055)-G (rs7087507)-A (rs10761600) was also
      significantly negatively associated with susceptibility to CAD (P=0.049).
      Moreover, these negative disease associations still existed after logistic
      regression analysis was taken into account to eliminate confounding conventional
      coronary risk factors. The results implicate possible disease relevance of the
      polymorphisms in the Mrf-2 gene with susceptibility to CAD. However, a larger
      scale prospective study is needed to clarify these findings.

PMID- 18612190
TI  - Prostaglandin F2alpha inhibits SERCA2 gene transcription through an induction of
      Egr-1 in cultured neonatal rat cardiac myocytes.
AB  - Prostaglandin F(2alpha) (PGF(2alpha)) stimulates hypertrophic growth of neonatal
      rat cardiac myocytes, a feature of which includes downregulation of the Ca(2+)
      ATPase (SERCA2), a major Ca(2+) transport protein in SR. The molecular mechanisms
      by which PGF(2alpha) inhibits SERCA2 gene expression remain unknown. We
      determined the cis-regulatory elements responsible for the regulation of the
      SERCA2 gene expression in cultured neonatal rat cardiac myocytes exposed to
      PGF(2alpha). The role of Egr-1 was evaluated by transient transfection of its
      expression vector and antisense oligonucleotide. Signaling pathways were
      determined by using the pharmacological inhibitors or cDNA expression plasmids
      coding for dominant negative forms of Ras and Rac. PGF(2alpha) reduced the SERCA2
      mRNA levels in a time- and dose-dependent manner in cultured rat cardiac
      myocytes. Transient transfection analyses showed that PGF(2alpha) -responsive
      elements are located between -284 and -72 of the SERCA2 promoter, which contains
      G+C-rich sequences homologous to Sp1, Egr-1 and AP2-binding sites. PGF(2alpha)
      significantly increased Egr-1 expression, and overexpression of Egr-1 largely
      reduced the transcription of the SERCA2 gene. Egr-1 antisense oligonucleotides
      blocked the PGF(2alpha) -mediated decrease in SERCA2 mRNA expression.
      Furthermore, inhibitors for either genistein-sensitive tyrosine kinase or p38
      MAPK, and dominant negative forms of either Ras or Rac, prevented PGF(2alpha) 
      induced repression of SERCA2 mRNA levels. These results suggest that Egr-1, as
      well as Ras, Rac, and p38 MAPK, plays a crucial role in the repression of SERCA2
      gene expression during PGF(2alpha) -induced cardiac hypertrophy.

PMID- 18612191
TI  - Protective effect of creatine supplementation and estrogen replacement on cardiac
      reserve function and antioxidant reservation against oxidative stress in exercise
      trained ovariectomized hamsters.
AB  - The combined effect of creatine (Cr) or estrogen (E(2)) with exercise training on
      cardiac reserve function and antioxidant reservation against oxidative stress
      were investigated in ovariectomized female Golden Syrian hamsters. One hundred
      animals were divided into nonexercise and exercise-trained groups, in which each
      group was separated into the control and 4 treatments of Cr depletion (Cr-), Cr
      supplementation (Cr+), E(2) replacement (E(2)), and Cr supplementation combined
      with E(2) replacement (Cr+E (2)). In the exercise-trained group, wheel-running
      exercise (10 minutes a day, 5 days a week) was imposed for 9 weeks. After the
      animals were sacrificed, several indicators of cardiac function, specifically the
      corrected QT interval, left ventricular developed pressure (LVDP), and maximum
      rate of rise (dP/dt(max)) against a hydrogen peroxide (H(2)O(2)) stress test were
      measured in isolated hearts using the Langendorff apparatus. Markers of oxidative
      stress, in other words, reduced glutathione (GSH), oxidized glutathione (GSSG),
      and an antioxidant enzyme, glutathione peroxidase (GPx) were determined. Exercise
      trained animals could restore cardiac reserve function and antioxidant levels
      against oxidative damage (P<0.05). Cr+, E(2) , and Cr+E(2) combined with exercise
      training showed highly protected cardiac reserve function against oxidative
      stress compared to Cr+, E(2) , and Cr+E(2) without exercise (P<0.05). The
      myocardial antioxidant levels were improved greatly in E(2) and Cr+E(2) combined
      with exercise training (P<0.05). In conclusion, estrogen replacement and creatine
      supplementation plus estrogen replacement when combined with exercise training
      show significant protective effects for cardiac reserve function and antioxidant
      reservation against oxidative stress in estrogen-deficient hamsters.

PMID- 18612192
TI  - Percutaneous coronary intervention versus coronary artery bypass graft surgery
      for the treatment of unprotected left main coronary artery stenosis: in-hospital
      and one year outcome after emergent and elective treatments.
AB  - This study attempts to compare the risks and benefits of provisional stenting
      with drug eluting stents and bypass surgery for left main coronary artery (LMCA)
      stenosis. Recent improvements in interventional technologies have increased
      interest in percutaneous treatment of LMCA stenosis. However, application of
      percutaneous techniques to LMCA has been sporadic and controversial. In-hospital
      and one year outcomes of coronary artery bypass graft (CABG) and percutaneous
      coronary intervention (PCI) cases were compared. From September, 2003 to June,
      2005, a total of 59 consecutive patients with de novo unprotected LMCA stenosis
      were treated with either CABG or PCI. Twenty patients received non-intravascular
      ultrasound-guided PCI with a stent in the LMCA. Thirty-nine patients underwent
      CABG. At 30-day follow-up, the major adverse cardiac and cerebrovascular event
      (MACE) rates of mortality, myocardial infarction, cerebral vascular accident, and
      target vessel revascularization were 25.6% in the CABG group and 5% in the PCI
      group (P=0.054). At one year follow-up, the MACE rates were 33.3% in the CABG
      group and 5% in the PCI group. One year MACE for the CABG group significantly
      differed from that of the PCI group (P=0.015). The odds ratio (OR) of one year
      MACE-free survival was 0.75 (P<0.001) in the CABG group versus the PCI group.
      Further analysis demonstrated there was a significant difference in in-hospital
      MACE and one year MACE between the elective CABG group and elective PCI group
      (P=0.045). However, there was no significant difference between the emergent CABG
      group and emergent PCI group (P=1.000 for in-hospital MACE; P=0.486 for one year
      MACE). PCI on unprotected LM offers an alternative option in patients with high
      surgical risk and appropriate lesion morphology.

PMID- 18612193
TI  - Infective endocarditis after alcohol septal ablation for obstructive hypertrophic
      cardiomyopathy.
AB  - Infective endocarditis (IE) is a relatively rare but serious complication of
      hypertrophic obstructive cardiomyopathy. Currently, antibiotic prophylaxis is not
      generally recommended in these patients. We report a case of infective
      endocarditis in a patient after alcohol septal ablation for hypertrophic
      obstructive cardiomyopathy with residual left ventricle outflow tract
      obstruction. To the best of our knowledge, this is the first case in the medical
      literature demonstrating this complication in the late postprocedural period
      following alcohol septal ablation.

PMID- 18612194
TI  - Postpartum complete atrioventricular block due to cardiac sarcoidosis: steroid
      therapy without permanent pacemaker.
AB  - A 32 year-old woman with bilateral hilar lymphadenopathy suffered from syncopal
      attacks after her first delivery. Electrocardiograms showed complete
      atrioventricular block (AVB) and myocardial scintigrams demonstrated a decreased
      uptake in the anteroseptal area. She was diagnosed as having postpartal cardiac
      acceleration of sarcoidosis. Because she rejected permanent pacemaker
      implantation, we started steroid therapy under temporary pacing. Fortunately, the
      treatment was very effective. Even after tapering-off of the steroid, the AVB has
      never reappeared. Permanent pacemaker implantation with subsequent steroid
      therapy is generally recommended for complete AVB due to cardiac sarcoidosis.
      However, steroid therapy alone can be considered for some selected cases.

PMID- 18612195
TI  - Long-term treatment with ranirestat (AS-3201), a potent aldose reductase
      inhibitor, suppresses diabetic neuropathy and cataract formation in rats.
AB  - We investigated the chronic functional and histopathological changes in the
      sciatic nerve and lens of streptozotocin (STZ)-diabetic rats and evaluated the
      preventive effects of ranirestat (AS-3201), a potent aldose reductase inhibitor,
      on these changes. Sorbitol levels in the sciatic nerve and lens, motor nerve
      conduction velocity (MNCV), and development of cataracts were measured in STZ
      diabetic rats given a ranirestat-admixed diet (0.0005%) for 35 weeks. Ranirestat
      reduced sorbitol accumulation in the sciatic nerve and improved the decrease in
      MNCV of STZ-diabetic rats. Morphological and morphometric examination of changes
      in sural nerve revealed that treatment with ranirestat prevented both the
      deformity of myelinated fibers and the decrease in their axonal and myelin areas
      (atrophy). Ranirestat also averted the changes in the size frequency histogram of
      myelinated fibers. Finally, STZ-diabetic rats developed early lens opacities 8
      weeks after STZ injection and had cataract by the end of the experimental period.
      However, in the ranirestat-treated diabetic rats, no lens opacity was observed in
      any rat throughout the entire experimental period. This study suggests that the
      polyol pathway plays an important role in the progress of diabetic neuropathy and
      cataract formation in STZ-diabetic rats. Ranirestat should be a promising agent
      for the treatment of complications associated with diabetes, especially
      neuropathy.

PMID- 18612196
TI  - Inhibitory effects of Eleutherococcus senticosus extracts on amyloid beta(25-35)
      induced neuritic atrophy and synaptic loss.
AB  - Neurons with atrophic neurites may remain alive and therefore may have the
      potential to regenerate even when neuronal death has occurred in some parts of
      the brain. This study aimed to explore effects of drugs that can facilitate the
      regeneration of neurites and the reconstruction of synapses even in severely
      damaged neurons. We investigated the effects of Eleutherococcus senticosus
      extracts on the regeneration of neurites and the reconstruction of synapses in
      rat cultured cortical neurons damaged by amyloid beta (Abeta)(25-35). Treatment
      with Abeta(25-35) (10 microM) induced axonal and dendritic atrophies and synaptic
      loss in cortical neurons. Subsequent treatment with the methanol extract and the
      water extract of E. senticosus (10 - 1000 ng/ml) resulted in significant axonal
      and dendritic regenerations and reconstruction of neuronal synapses. Co
      application of the extract and Abeta(25-35) attenuated Abeta(25-35)-induced
      neuronal death. We investigated neurite outgrowth activities of eleutherosides B
      and E and isoflaxidin, which are known as major compounds in E. senticosus.
      Although eleutheroside B protected against Abeta(25-35)-induced dendritic and
      axonal atrophies, the activities of eleutheroside E and isofraxidin were less
      than that of eleutheroside B. Although the contents of these three compounds in
      the water extract were less than in the methanol extract, restoring activities
      against neuronal damages were not different between the two extracts. In
      conclusion, extracts of E. senticosus protect against neuritic atrophy and cell
      death under Abeta treatment, and one of active constituents may be eleutheroside
      B.

PMID- 18612197
TI  - Expression of hedgehog family genes in the rat uterus during early pregnancy.
AB  - Hedgehog (Hh) plays a pivotal role in various tissues during embryonic
      development, tissue homeostasis and tumorigenesis. In mammals, Hh exists in three
      homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh).
      In this study, we cloned full-length cDNAs encoding Dhh and Ihh from the rat
      uterus. Their amino acid sequences have a high homology with those of the mouse
      and human. In addition, the changes of Hh gene expression in the rat uterus
      during early pregnancy were analyzed. The results showed that all three hedgehog
      mRNAs were detected in the rat uterus at the proestrus stage and during early
      pregnancy (1.5, 3.5, 5.5 and 7.5 days post coitus: dpc). Ihh mRNA expression
      varied and peaked at 3.5 dpc in the luminal and glandular epithelium. Expression
      was decreased on 5.5 dpc with the exception of sustained expression in the
      glandular epithelium. Despite such Ihh variability, the expressions of Dhh and
      Shh mRNA remained unchanged. This indicated that Ihh was mainly expressed in the
      rat uterus during early pregnancy. Moreover, the Hh target gene (glioma
      associated oncogene homolog 1; Gli1) was also highly expressed at 3.5 dpc in the
      epithelium and periepithelial stroma in a manner similar to the temporal pattern
      of Ihh expression. This suggests that Ihh signaling axis play a role in the rat
      uterus during early pregnancy. In summary, our results elucidate that Ihh is a
      predominant Hh protein in the rat uterus during early pregnancy and that other
      Hhs have the potential to be expressed. This observation will help to elucidate
      the basic molecular mechanism of rat uterus during early pregnancy.

PMID- 18612198
TI  - Schnitzler's syndrome: monoclonal gammopathy associated with chronic urticaria.
AB  - Schnitzler's syndrome (SS) is defined by monoclonal gammopathy and chronic
      urticaria combined with at least two of the following features: fever, arthralgia
      or arthritis, bone pain, hepato- and/or splenomegaly, palpable lymph nodes,
      elevated ESR, and leukocytosis. We report a 49-year-old man with monoclonal IgM
      gammopathy and a 4-year history of recurrent urticarial rash, unexplained fever
      and arthralgias. The skin biopsy from an acute lesion revealed perivascular
      lymphocytic infiltrates consisting of CD4+ and CD8+ T lymphocytes. To our
      knowledge, this is the first report of an immunophenotypic characterization of
      skin infiltrates in SS. A lower CD4+/CD8+ ratio of circulating T lymphocytes was
      also detected. SS usually has a benign course, but in 15% of patients a
      lymphoproliferative disorder develops.

PMID- 18612199
TI  - Dyslipidemia in chronic kidney disease: an approach to pathogenesis and
      treatment.
AB  - BACKGROUND/AIMS: Cardiovascular disease (CVD) is a major cause of mortality in
      patients with mild to moderate chronic kidney disease (CKD) and end-stage renal
      disease (ESRD). Dyslipidemia has been established as a well-known traditional
      risk factor for CVD in the general population and it is well known that patients
      with CKD exhibit significant alterations in lipoprotein metabolism. In this
      review the pathogenesis and treatment of renal dyslipidemia are discussed.
      METHODS: Studies on lipid abnormalities in CKD stages 1-4, in nephrotic syndrome,
      and in hemodialysis and peritoneal dialysis patients are analyzed, as well as the
      lipid profile of kidney graft recipients. Also, the results of the effects of
      epoietin treatment and hypolipidemic drugs in CKD patients are reported. RESULTS:
      Disturbances in lipoprotein metabolism are evident even at the early stages of
      CKD and usually follow a downhill course that parallels the decline of renal
      function. However, several intrinsic or exogenous factors can influence the
      phenotypic expression of these alterations. According to the literature, current
      evidence suggests that unlike dialysis patients, mild to moderate CKD patients
      could be benefit from the use of statins. CONCLUSION: The use of statins is
      indicated in patients with mild to moderate CKD, while in subjects with ESRD
      lipid-lowering therapy should be individualized.

PMID- 18612200
TI  - Putative role of endothelial lipase in dialysis patients with hypoalbuminemia and
      inflammation.
AB  - BACKGROUND/AIMS: A recent study suggests that inflammation and malnutrition are
      strongly associated with cardiovascular disease in dialysis patients. Endothelial
      lipase (EL) is a newly cloned physiological regulator of high-density lipoprotein
      cholesterol (HDL), which is associated with the progression of atherosclerosis.
      To clarify the role of EL in dialysis patients, we evaluated serum markers on the
      basis of the presence of hypoalbuminemia and inflammation. METHODS: We divided
      the 97 study patients into two groups on the basis of serum albumin (Alb) and
      high-sensitive C-reactive protein (hsCRP) levels, and measured serum EL levels.
      Serum EL levels were significantly correlated with Alb, cholinesterase, log
      hsCRP, and log tumor necrosis factor-alpha. They were also assigned to one of
      three groups on the basis of hypoalbuminemia and inflammatory status. RESULTS:
      Serum EL levels were significantly higher and serum HDL levels were lower in
      patients with low serum Alb and/or high hsCRP levels than in those without these
      abnormalities. Furthermore, when patients were classified into two groups on the
      basis of the EL levels measured, cardiovascular disease events during the 2-year
      follow-up period were significantly greater in the group with higher EL levels.
      CONCLUSIONS: Our findings suggest that the link between EL, hypoalbuminemia and
      inflammation may play an important role in atherogenesis in dialysis patients.

PMID- 18612201
TI  - Mortality and reinfarction among patients using different beta-blockers for
      secondary prevention after a myocardial infarction.
AB  - OBJECTIVES: To study differences in the clinical efficacy of various brands of
      beta-blocker in secondary prevention after a myocardial infarction (MI). METHODS:
      All patients hospitalized with a first MI between 1995 and 2002 who were still
      alive 30 days after discharge and had had at least one prescription for a beta
      blocker filled were identified by individual-level linkage of nationwide
      registries of hospitalizations and drugs dispensed from pharmacies. A total of
      32,259 MI patients were included in the study. Multivariable Cox proportional
      hazard models were used to analyze the risks of death and recurrent MI related to
      treatment with different beta-blockers. RESULTS: The risks for death and
      recurrent MI were similar in patients using different beta-blockers, except that
      mortality from all causes among patients with a prescription for sotalol was
      higher. Subgroup analyses of high-risk patients with diabetes or congestive heart
      failure and of patients using comparable dosages of beta-blockers did not show
      effects on the risk of death or recurrent MI. CONCLUSION: Except for sotalol, the
      different types of beta-blocker had similar clinical efficacy in reducing
      mortality and the recurrence of MI. The equivalent efficacy remained when high
      risk patients were analyzed separately.

PMID- 18612202
TI  - Relation between AT1R gene polymorphism and long-term outcome in patients with
      heart failure.
AB  - OBJECTIVES: Angiotensin II plays a key role in the pathophysiology of heart
      failure (HF). This study examined the angiotensin II type 1 receptor (AT1R)
      polymorphism in patients with systolic HF and its relation to clinical
      manifestations and patient outcome. METHODS: We genotyped 134 patients with HF
      and reduced systolic function for the AT1R A1166C genotype using polymerase chain
      reaction and restriction fragment length polymorphism. We analyzed the
      relationship between the AT1R A1166C polymorphism and clinical,
      electrocardiographic, echocardiographic and laboratory parameters in patients
      with ischemic and non-ischemic etiology and examined the relation between the
      AT1R genotype and long-term (30 months) patient survival. RESULTS: In HF
      patients, frequency of the AT1R 1166C allele and specifically the CC genotype was
      similar to the general population, but associated with an ischemic and not a non
      ischemic etiology (p = 0.02). The CC genotype was associated with more advanced
      disease and more severe abnormalities of renal function (p = 0.008). Survival
      analysis showed that AT1R CC homozygous patients had significantly higher
      mortality (p = 0.008; adjusted odds ratio for mortality 6.35, 95% confidence
      interval 1.49-11.21, p = 0.01). CONCLUSION: The CC AT1R genotype was associated
      with poor prognostic markers and increased mortality. The findings support the
      principle of genome-based therapies in the future treatment of HF patients.

PMID- 18612203
TI  - Stem cells, tissue regeneration and repair. Preface.

PMID- 18612204
TI  - Conducting labor in women with previous caesarean section in a low gestational
      week. A prospective case-controlled study.
AB  - AIMS: To assess whether vaginal labor after a previous caesarean section in a low
      gestational week performed by means of a high placed U-section technique could be
      recommended by obstetricians as a sufficiently safe method of choice for pregnant
      women. METHODS: Of 309 pregnant women with a history of a high placed U-section,
      166 (53.7%) met the criteria for the subsequent vaginal delivery and agreed with
      it. In 78%, vaginal labor started spontaneously and in 22% it was induced due to
      postterm pregnancy or preterm rupture of membranes. RESULTS: Vaginal labor was
      successful in 72.3% of women. Deliveries after spontaneous onset of uterine
      contractions (80%) were considerably more successful. In the group of women with
      induced labor, the success rate was below 50%. Uterine rupture was not
      encountered in the study group. CONCLUSIONS: Vaginal labor after a previous high
      placed U-section is a sufficiently safe method of choice for selected groups of
      pregnant women, but it has to be mentioned that selecting criteria can only
      minimize and not entirely exclude the risk of uterine rupture.

PMID- 18612205
TI  - LPA and PLG sequence variation and kringle IV-2 copy number in two populations.
AB  - BACKGROUND/AIMS: Lp(a) levels have long been recognized as a potential risk
      factor for coronary heart disease that is almost completely under genetic
      control. Much of the genetics impacting Lp(a) levels has been attributed to the
      highly polymorphic LPA kringle IV-2 copy number variant, and most of the variance
      in Lp(a) levels in populations of European-descent is inversely correlated with
      kringle IV copy number. However, less of the variance is explained in African
      descent populations for the same structural variation. African-descent
      populations have, on average, higher levels of Lp(a), suggesting other genetic
      factors contribute to Lp(a) level variability across populations. METHODS: To
      identify potential cis-acting factors, we re-sequenced the gene LPA for single
      nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African
      Americans. We also re- sequenced the neighboring gene plasminogen (PLG) and
      genotyped the kringle IV copy number variant in the same reference samples.
      RESULTS: These data are the most comprehensive description of sequence variation
      in LPA and its relationship with the kringle IV copy number variant. With these
      data, we demonstrate that only a fraction of LPA sequence diversity has been
      previously documented. Also, we identify several high frequency SNPs present in
      the African-American sample but absent in the European-American sample. Finally,
      we show that SNPs within PLG are not in linkage disequilibrium with SNPs in LPA,
      and we show that kringle IV copy number variation is not in linkage
      disequilibrium with either LPA or PLG SNPs. CONCLUSIONS: Together, these data
      suggest that LPA SNPs could independently contribute to Lp(a) levels in the
      general population.

PMID- 18612206
TI  - Power of genetic association studies in the presence of linkage disequilibrium
      and allelic heterogeneity.
AB  - OBJECTIVES: The calculation of the power and sample size required for association
      studies is essential, particularly for follow-up of genome-wide association
      studies, where much genotyping is required to replicate the original finding and
      identify the true disease susceptibility mutation. METHODS: In this paper, we
      derive equations for estimation of sample sizes for the transmission
      disequilibrium test (TDT) and for case-control studies, in the presence of
      allelic heterogeneity and indirect association - where the genotyped tagging SNP
      is in linkage disequilibrium (LD) with the true mutation. Using data from NOD2
      and PTPN22, we show that the true sample sizes required to detect association may
      be incorrect when calculated under the assumption of a single mutation and
      complete LD with the genotyped marker. RESULTS: The true sample sizes may be
      lower when allelic heterogeneity acts in a recessive model across mutations, or
      increased when mutations lie on different alleles of a common tagging SNP.
      CONCLUSION: Calculating power and sample size under a range of realistic models
      of LD and allelic heterogeneity is essential to ensure that association studies
      have sufficient power to detect mutations.

PMID- 18612207
TI  - Practical considerations for dividing data into subsets prior to PPL analysis.
AB  - OBJECTIVE: The PPL, a class of statistics for complex trait genetic mapping in
      humans, utilizes Bayesian sequential updating to accumulate evidence for or
      against linkage across potentially heterogeneous data (sub)sets. Here, we
      systematically explore the relative efficacy of alternative subsetting approaches
      for purposes of PPL calculation. METHODS: We simulated genotypes for three
      pedigree sets (sib pairs; 2-3 generations; >or=4 generations) based on families
      from an ongoing study. For each pedigree set, 100 replicates were generated under
      different levels of heterogeneity (1000 under 'no linkage'). Within each
      replicate, updating was performed across subsets defined randomly (RAND2, RAND4),
      by true (TRUE) linkage status, with a realistic (REAL) classification, by
      individual pedigree (PED), or without any subsetting (NONE). RESULTS: Under
      'linkage', REAL yields larger PPLs compared to NONE, RAND2, RAND4, or PED. Under
      'no linkage', RAND2, RAND4 and PED yield PPLs close to NONE. CONCLUSIONS: We have
      examined the impact of different subsetting strategies on the sampling behavior
      of the PPL. Our results underscore the utility of finding variables that can help
      delineate more homogeneous data subsets and demonstrate that, once such variables
      are found, sequential updating can be highly beneficial in the presence of
      appreciable heterogeneity at a linked locus, without inflation at an unlinked
      locus.

PMID- 18612208
TI  - Estimating disease risk associated with mutated genes in family-based designs.
AB  - OBJECTIVE: Many clinical decisions require accurate estimates of disease risk
      associated with inherited gene mutations. While several family-based designs have
      been proposed, their relative advantages remain unclear. METHODS: We considered
      four commonly-used family-based designs and evaluated their performance in terms
      of accuracy and efficiency under several genetic models via simulation studies.
      We also derived and assessed several ascertainment-corrected likelihood methods
      for analyzing the simulated data and real data from 12 HNPCC pedigrees from
      Newfoundland. RESULTS: We found that the design efficiency depends on the
      question of interest: the clinic-based family design with random probands yields
      the most efficient estimate of genetic relative risks, whereas the population
      based family design with mutation carrier probands provides the most efficient
      penetrance estimates. For a particular question, an ascertainment correction
      seems possible using regular likelihood methods but the presence of genetic
      heterogeneity due to a strong second gene effect can lead to some bias in the
      risk estimation. CONCLUSIONS: This work gives a general methodological framework
      for analyzing family-based designs in gene characterization studies and provides
      more rationale for the choice of an efficient design and an appropriate
      likelihood method to estimate the risk associated with an inherited gene
      mutation.

PMID- 18612209
TI  - Inflammatory gene haplotype-interaction networks involved in coronary collateral
      formation.
AB  - OBJECTIVES: Formation of collateral circulation is an endogenous response to
      atherosclerosis, and is a natural escape mechanism by re-routing blood.
      Inflammatory response- related genes underlie the formation of coronary
      collaterals. We explored the genetic basis of collateral formation in man
      postulating interaction networks between functional Single Nucleotide
      Polymorphisms (SNPs) in these inflammatory gene candidates. METHODS: The
      contribution of 41 genes as well as the interactions among them was examined in a
      cohort of 226 coronary artery disease patients, genotyped for 54 candidate SNPs.
      Patients were classified to the extent of collateral circulation. Stepwise
      logistic regression analysis and a haplotype entropy procedure were applied to
      search for haplotype interactions among all 54 polymorphisms. Multiple testing
      was addressed by using the false discovery rate (FDR) method. RESULTS: The
      population comprised 84 patients with and 142 without visible collaterals. Among
      the 41 genes, 16 pairs of SNPs were implicated in the development of collaterals
      with the FDR of 0.19. Nine SNPs were found to potentially have main effects on
      collateral formation. Two sets of coupling haplotypes that predispose to
      collateral formation were suggested. CONCLUSIONS: These findings suggest that
      collateral formation may arise from the interactions between several SNPs in
      inflammatory response related genes, which may represent targets in future
      studies of collateral formation. This may enhance developing strategies for risk
      stratification and therapeutic stimulation of arteriogenesis.

PMID- 18612210
TI  - Editorial note: sources of neonatal medicine.

PMID- 18612211
TI  - History of neonatal resuscitation. Part 1: Artificial ventilation.
AB  - The construction of manual ventilators by Hunter, Chaussier, and Gorcy seemed to
      set the stage for artificial ventilation of the neonate at the end of the 18th
      century. When Leroy d'Etiolles recognized pneumothorax as a complication of
      ventilation in 1828, the Paris Academy of Science advised against positive
      pressure ventilation. Indirect techniques like that of Silvester or the Schultze
      swingings gained widespread acceptance and prevailed until the First World War.
      Modern ventilators were developed following the poliomyelitis epidemics in the
      20th century.

PMID- 18612212
TI  - Refining the method of therapeutic lung lavage in meconium aspiration syndrome.
AB  - BACKGROUND: Therapeutic lung lavage is an emerging treatment for meconium
      aspiration syndrome (MAS), but the ideal fluid volume and lavage technique remain
      unclear. OBJECTIVE: To evaluate the impact of suction technique, chest squeeze
      and aliquot volume on the efficacy of lung lavage in MAS. METHODS: MAS was
      induced in ventilated 2-week-old piglets using 4 ml/kg of 20% human meconium.
      Lung lavage with either two 8 ml/kg saline aliquots (n = 5) or a single 15 ml/kg
      aliquot (n = 6) was performed soon after meconium instillation. Lavage fluid was
      recovered by three methods performed in sequence: closed suction via a suction
      adaptor; open suction with the ventilator disconnected, and open suction with
      manual vibratory chest squeezing. Return fluid was collected separately with each
      method. Recovery of meconium and lavage fluid was determined and expressed as a
      proportion of the amount instilled. RESULTS: Closed suction resulted in poor
      meconium and fluid returns, with recovery of meconium being only 5.2 +/- (SD)
      2.5% with 2 x 8 ml/kg lavage and 19 +/- 11% with a single 15 ml/kg aliquot. Chest
      squeeze during suction increased recovery of both meconium and lavage fluid.
      Overall recovery of instilled meconium was greater with 15 ml/kg lavage (45 +/-
      17%) than with two 8 ml/kg aliquots (24 +/- 4.5%, p = 0.028, repeated-measures
      ANOVA); the corresponding values for return of lavage fluid were 73 +/- 10 and 49
      +/- 13%, respectively (p < 0.01). CONCLUSIONS: Open suction, vibratory chest
      squeezing and an aliquot volume of 15 ml/kg each improve the efficacy of lung
      lavage in MAS, and merit inclusion in the lavage technique in clinical trials of
      this therapy.

PMID- 18612213
TI  - Postnatal administration of dexamethasone for weaning off the ventilator affects
      thyroid function.
AB  - BACKGROUND: Very preterm neonates are at risk of hypothyroxinemia because of
      prematurity as well as because of neonatal disease. Hypothyroxinemia is
      associated with impaired developmental outcome. Preterm infants who cannot be
      weaned from the ventilator can be treated with dexamethasone. Glucocorticoid
      administration has been found to alter thyroid hormone parameters. Therefore,
      dexamethasone treatment in these infants might additionally impair their thyroid
      function, which could have consequences for developmental outcome. OBJECTIVE: To
      assess what changes in thyroid function occur in the first hours after initiating
      dexamethasone treatment in ventilated preterm infants. METHODS: Preterm infants,
      in whom the decision was taken to start dexamethasone treatment, were included.
      Thyroxine (T(4)), 3,5,3'-triiodothyronine (T(3)), reverse T(3) (rT(3)), thyroid
      stimulating hormone (TSH) and cortisol were determined before and 6-9 h after
      administration of the first dose of a postnatal dexamethasone course. Details of
      clinical condition were recorded at both time points. RESULTS: Sixteen very
      preterm infants were included at a median age of 20 days. While clinical
      condition was stable between start of dexamethasone and 6-9 h thereafter, TSH and
      T(3) levels decreased significantly. rT(3) levels significantly increased,
      resulting in a decrease in the T(3)/rT(3) ratio. There was no statistically
      significant effect on the levels of T(4). CONCLUSION: Postnatal dexamethasone
      administration negatively affects thyroid functioning the preterm infant with
      severe chronic lung disease.

PMID- 18612214
TI  - Suppression and recovery of the hypothalamic function after high-dose
      corticosteroid treatment in preterm infants.
AB  - BACKGROUND: High-dose systemic dexamethasone is effective in facilitating
      extubation of ventilated infants with bronchopulmonary dysplasia. Although the
      suppression and recovery of pituitary-adrenal response had been assessed after
      corticosteroid treatment in very low birth weight infants, its effect on
      hypothalamic function has not been longitudinally monitored. AIMS: This study was
      designed to assess the longitudinal hypothalamic response before, during and 4
      weeks after a 3-week dose-tapering course of systemic dexamethasone treatment.
      PATIENTS AND METHODS: Twenty very low birth weight infants had blood collected
      for corticotropin-releasing hormone, ACTH and cortisol measurements immediately
      before starting dexamethasone (week 0), after receiving the maximum dose of
      treatment (week 1), at the end of the 3-week course (week 3) and 4 weeks after
      stopping corticosteroids (week 7). RESULTS: All circulating hormone
      concentrations were significantly suppressed during the treatment period at week
      1 and week 3 compared with pretreatment concentrations at week 0 (p < 0.001). The
      recovery of pituitary function started early soon after week 1, whereas that of
      hypothalamus and adrenal functions started after the end of the dexamethasone
      course. Plasma ACTH concentration at week 7 had returned to the pretreatment
      level, but plasma corticotropin-releasing hormone (p < 0.05) and serum cortisol
      (p < 0.001) concentrations remained significantly suppressed. Partial recovery of
      hypothalamic and adrenal function was observed at week 7 (62 vs. 36% of their
      pretreatment levels, respectively). CONCLUSION: Our findings suggest that the
      hypothalamic function is suppressed during systemic corticosteroid treatment but
      partial recovery occurs 4 weeks after stopping therapy. Even in preterm infants,
      the hypothalamic-pituitary-adrenal axis behaves in a similar manner as in adult
      subjects and the pituitary function recovers earlier than that of hypothalamus
      and adrenals.

PMID- 18612215
TI  - Resuscitation of newborn infants with 21% or 100% oxygen: an updated systematic
      review and meta-analysis.
AB  - BACKGROUND: The issue of whether 21% O(2) is more effective than 100% O(2) for
      resuscitation of newborn infants remains controversial. OBJECTIVES: We have
      updated the systematic review and meta-analysis including all studies reporting
      resuscitation of newborn infants with 21 or 100% O(2). METHODS: Randomized or
      quasi-randomized studies of depressed newborn infants resuscitated with 21 or
      100% O(2) with or without masking of treatment were considered for inclusion. The
      outcomes of interest included neonatal mortality and hypoxic ischemic
      encephalopathy. RESULTS: Ten studies fulfilled the inclusion criteria. Of these,
      6 studies were identified as being strictly randomized. In total, 1,082 infants
      were allocated to resuscitation with 21% O(2) and 1,051 infants with 100% O(2).
      The risk of neonatal mortality was reduced in the 21% O(2) group compared to the
      100% O(2 )group both in the analysis of all studies (typical RR 0.69, 95% CI
      0.54, 0.88) and in the analysis of strictly randomized studies (typical RR 0.32,
      95% CI 0.12, 0.84). A trend toward a decrease in the risk of hypoxic ischemic
      encephalopathy stage 2 and 3 was noted with resuscitation in 21% O(2) in the
      analysis of all studies (typical RR 0.88, 95% CI 0.72, 1.08). CONCLUSIONS: There
      is a significant reduction in the risk of neonatal mortality and a trend towards
      a reduction in the risk of severe hypoxic ischemic encephalopathy in newborns
      resuscitated with 21% O(2).

PMID- 18612216
TI  - Serum beta2-microglobulin as a marker of congenital toxoplasmosis and
      cytomegalovirus infection in preterm neonates.
AB  - BACKGROUND: Fetal serum beta(2)-microglobulin (beta(2)M) has been reported as a
      reliable indicator of fetal infectious diseases. OBJECTIVES: To evaluate serum
      beta(2)M as a marker of congenital toxoplasmosis or cytomegalovirus (CMV)
      infection in neonates. METHODS: beta(2)M was retrospectively measured in 72
      neonatal serum samples from preterm neonates. Of these, 32 originated from
      neonates with serological evidence of congenital toxoplasmosis (n = 12) and CMV
      infection (n = 20), while 40 samples from neonates in which both infections were
      serologically excluded served as controls. beta(2)M levels were compared between
      the infection and control groups. RESULTS: Mean (+/-SEM) beta(2)M levels were
      significantly higher in the groups of neonates infected with Toxoplasma (5.64 +/-
      0.61 mg/l) (p = 0.014) and CMV (6.06 +/- 0.66 mg/l) (p < 0.0001) than in the
      control group (3.80 +/- 0.2). Against the cut-off level of 5 mg/l, beta(2)M was
      normal in 36 of the 40 uninfected neonates examined, indicating a specificity of
      90%. In contrast, it was elevated in 66.7% (8/12) and 65% (13/20) of the
      Toxoplasma and CMV-infected neonates, respectively, indicating an overall
      sensitivity of 66%. CONCLUSIONS: In the absence of urogenital disorders, an
      increase in beta(2)M in neonates is likely to be infection-induced. We showed
      that serum beta(2)M is increased in congenital toxoplasmosis and CMV infection in
      the first weeks of life.

PMID- 18612217
TI  - Molecular characterization of inflammation and Staphylococcus aureus colonization
      of involved skin of atopic dermatitis patients. A non-invasive approach.
AB  - Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease mainly
      stemming from a genetic predisposition that leads to hypersensitivity to
      environmental factors and a common involvement of Staphylococcus aureus (SA)
      colonization. The aim of this work was to propose a new non-invasive approach to
      enumerate the genes coding for the toxins of SA in atopic skin samples. In
      parallel, the study aimed to evaluate the change in AD through 3 markers of the
      inflammatory response: IL-8, IL-1RA/IL-1alpha and IL-18. These methods were
      tested on 31 patients with AD, and finally on a group of 19 subjects for whom
      clinical improvement had been reported after various treatments. The study
      revealed the presence of a large number of genes encoding toxins in atopic
      samples, indicating a high rate of SA colonization, and also an increase in the
      level of all cytokine markers in atopic skin compared to the skin of healthy
      subjects. Finally, we found a positive correlation between increases in the
      SCORAD (Scoring Atopic Dermatitis Index) value after treatment and the
      corresponding evolution of the SA density. These methods provide a means to
      clinically evaluate the course of AD, and may help in the development of
      potential treatments.

PMID- 18612218
TI  - Targeting CD44v6 expressed in head and neck squamous cell carcinoma: preclinical
      characterization of an 111In-labeled monoclonal antibody.
AB  - In patients with head and neck squamous cell carcinoma (HNSCC)
      radioimmunodiagnosis could offer a more specific and sensitive tumor diagnostic
      method. Our aim was to evaluate the labeling and biodistribution of the novel
      radioimmunoconjugate (111)In-cMAb U36. In this study cMAb U36, targeting CD44v6,
      and huA33, as a negative control, were labeled with indium-111, using the
      chelator CHXA''-DTPA. Immunoreactivity assays and binding studies were performed
      in vitro. Biodistribution and tumor imaging were conducted after intravenous
      injection of the radioimmunoconjugate to nude mice bearing HNSCC xenografts
      expressing CD44v6. The immunoreactive fraction was very high and the binding was
      CD44v6-specific. In vivo results demonstrated a promising biodistribution, with
      tumors clearly accumulating radioactivity with time. At 168 h postinjection
      (p.i.) the tumor uptake was 54.7 +/- 16.6% injected dose/g. The cMAb U36 had
      significantly (p < 0.05) higher uptake in tumors 72 h p.i. compared to huA33. We
      produced a novel radioimmunoconjugate targeting CD44v6 for possible use in the
      detection of HNSCC. The conjugate demonstrates no adverse effects from labeling
      and a favorable biodistribution.

PMID- 18612219
TI  - Role of p53 codon 72 arginine allele in cell survival in vitro and in the
      clinical outcome of patients with advanced breast cancer.
AB  - BACKGROUND: The p53 codon 72 polymorphism, which results in either an arginine or
      proline residue, plays a different role in vitro and in vivo in cell survival and
      drug resistance. We verified, in vitro, the impact of the arginine allele on cell
      survival under normoxia and hypoxia, and investigated in vivo the role of p53
      codon 72 arginine homozygosity in the clinical outcome of advanced breast cancer
      patients. METHODS: Tumors at advanced stages grow in vivo in a hypoxic
      environment, and we mimicked such conditions in vitro using p53 null breast
      cancer cells transfected with either the arginine or proline allele. We also
      analyzed in vivo the p53 codon 72 genotype status of advanced breast cancer
      patients. RESULTS: In vitro transfection of the arginine allele induced higher
      cell death under normoxia, whereas cell death was greater in proline-transfected
      cells under hypoxia. The arginine allele upregulated BCRP-I, a hypoxia response
      gene, which increases drug resistance. Metastatic breast cancer patients
      homozygous for arginine had a significantly shorter time to progression and
      overall survival than those with heterozygous arginine/proline tumors.
      CONCLUSION: We provide a molecular explanation for the association of the
      arginine allele with tumor aggressiveness and treatment resistance in advanced
      breast cancer.

PMID- 18612220
TI  - Expression of CD44 is associated with a metastatic pattern of human neuroblastoma
      cells in a SCID mouse xenograft model.
AB  - Expression of CD44, a transmembrane glycoprotein involved in cell-cell and cell
      matrix interactions, has been associated with growth and metastatic behavior in
      several malignant tumors. In contrast to most other malignancies, in which up
      regulation of CD44 is related to tumor progression, the absence of CD44
      expression characterizes the aggressiveness of neuroblastomas in clinical
      studies. In this study, cells of human neuroblastoma cell lines (IMR-32, Kelly,
      LAN-1, LAN-5, LS, SH-SY5Y and SK-N-SH) were injected subcutaneously into SCID
      mice, and their growth behavior and CD44 expression were analyzed. All
      neuroblastoma cells engrafted in the SCID mouse, but primary tumor growth and
      metastatic potential varied considerably. Expression of CD44 was associated with
      a metastatic pattern of the neuroblastoma cell lines. CD44-positive
      neuroblastomas produced multicellular metastases predominantly located in the
      intra- and periarterial space of the lung. CD44-negative neuroblastomas developed
      numerous micrometastases in the lung interstitium. In conclusion, the entire
      spectrum of metastatic patterns can be modeled in SCID mice using the human
      neuroblastoma cell lines employed in this study. Our xenograft model provides a
      platform for investigating the complex processes involved in metastasis formation
      and for testing new anti-metastatic drugs. In particular, the role of CD44 in the
      formation of metastasis can be evaluated.

PMID- 18612222
TI  - A simple new method for identifying the proximal cut end in lower canalicular
      laceration.
AB  - PURPOSE: We report a simple and effective method of identifying the medial cut
      end of lower canalicular laceration cases. METHODS: Twenty-seven eyes with lower
      canalicular lacerations as a result of trauma were involved in the study. Surgery
      was performed within 48 hours after injury for canalicular reconstruction. Upper
      canalicular probing was utilized to identify the medial cut end of deep
      canalicular lacerations when difficulties were encountered. Total time from the
      initiation of the probing procedure to the identification of the medial cut end
      of the lower canaliculus was measured. RESULTS: A total of 27 eyes with lower
      canalicular lacerations were reconstructed. In 20 eyes, the medial lacerated end
      was located by upper canalicular probing. The mean time from initiation of the
      probing procedure to identification of the medial cut end of the lacerated
      canaliculus was 2 minutes. CONCLUSIONS: We conclude that upper canalicular
      probing in patients with lower canalicular lacerations significantly reduces the
      time from the initiation of the operation to the identification of the medial cut
      end of the lower canaliculus.

PMID- 18612223
TI  - The prevalence and demographic characteristics of anterior polar cataract in a
      hospital-based study in Korea.
AB  - PURPOSE: Anterior Polar Cataract (APC) develops by a mechanism different from
      that of other age-related cataracts, and outside of Korea, it is an extremely
      rare condition. We investigated the prevalence and epidemiological
      characteristics of APC in Koreans. METHODS: The evaluation on the prevalence of
      APC in comparison to the other age-related cataracts was performed on the 2,108
      cataract patients who were treated at 5 different areas in Korea from August 2003
      to December 2003. The demographic characteristics of APC were studied on the, 656
      cataract patients who were treated from January 2004 to January 2005 at one
      hospital. These patients were classified according to the type of lens opacity
      (nuclear, cortical, posterior subcapsular, mixed and APC). RESULTS: The
      prevalence of patients with APC among all the cataract patients was 6.02% during
      the 5 months in this hospital-based study. Eighty-seven per cent of patients with
      APC were male. In contrast, the proportion of female was greater than 50% in the
      other cataracts. The mean age of APC patients was 52.7 years. Among the APC
      patients, 38.9% were under 50 years of age, 42.6% in their 50s, 14.8% in their
      60s, and 3.7% were in their 70s. However, 80% of patients were over the age of 60
      years in nuclear, cortical, and mixed-type cataracts. CONCLUSIONS: The prevalence
      of APC among all cataracts was high in comparison with another country. The
      proportion of APC was high in individuals younger than 60 years of age, and in
      males.

PMID- 18612221
TI  - Alpha-fetoprotein, stem cells and cancer: how study of the production of alpha
      fetoprotein during chemical hepatocarcinogenesis led to reaffirmation of the stem
      cell theory of cancer.
AB  - Identification of the cells in the liver that produce alpha-fetoprotein during
      development, in response to liver injury and during the early stages of chemical
      hepatocarcinogenesis led to the conclusion that maturation arrest of liver
      determined tissue stem cells was the cellular process that gives rise to
      hepatocellular carcinomas. When the cellular changes in these processes were
      compared to that of the formation of teratocarcinomas, the hypothesis arose that
      all cancers arise from maturation arrest of tissue-determined stem cells. This
      was essentially a reinterpretation of the embryonal rest theory of cancer whereby
      tissue stem cells take the role of embryonal rests. A corollary of the stem cell
      theory of the origin of cancer is that cancers contain the same functional cell
      populations as normal tissues: stem cells, transit-amplifying cells and mature
      cells. Cancer stem cells retain the essential feature of normal stem cells: the
      ability to self-renew. Growth of cancers is due to continued proliferation of
      cancer transit-amplifying cells that do not differentiate to mature cells
      (maturation arrest). On the other hand, cancer stem cells generally divide very
      rarely and contribute little to tumor growth. However, the presence of cancer
      stem cells in tumors is believed to be responsible for the properties of
      immortalization, transplantability and resistance to therapy characteristic of
      cancers. Current therapies for cancer (chemotherapy, radiotherapy,
      antiangiogenesis and differentiation therapy) are directed against the cancer
      transit-amplifying cells. When these therapies are discontinued, the cancer
      reforms from the cancer stem cells. Therapy directed toward interruption of the
      cell signaling pathways that maintain cancer stem cells could lead to new
      modalities to the prevention of regrowth of the cancer.

PMID- 18612224
TI  - Clinical evaluation of accommodative intraocular lens implantation in high myopic
      eyes.
AB  - PURPOSE: To compare the clinical outcome of AT-45 implantation between high
      myopic eyes and non-high myopic eyes. METHODS: Retrospective, non-randomized,
      comparative trial. The medical charts of 28 patients with 35 eyes who had
      phacoemulsification and AT-45 implantation were retrospectively reviewed. 13 eyes
      of 10 patients were included in the high myopic group (axial length > or = 26.0
      mm) and 22 eyes of 18 patients were included in the non-high myopic group. The
      clinical data included unilateral best-corrected visual acuity (BCVA) and
      distance-corrected near visual acuity (DCNVA) at 6 months follow-up after the
      surgery. The results were compared between the two groups. RESULTS: In the non
      high myopic group, 22 eyes (100%) and 19 eyes (86.4%) achieved a BCVA of 20/25
      and 20/20 or better respectively. For the high myopic group, the results were 13
      eyes (100%) and 12 eyes (92.3%) respectively, at 6 months after the surgery. In
      the non-high myopic group, 21 (95.4%) and 7 eyes (31.8%) achieved a DCNVA of
      20/40 and 20/25 or better. For the high myopic group, the results were 13 (100%)
      and 4 eyes (30.8%) respectively, at 6 months after the surgery, the differences
      between the two groups for a BCVA of 20/25 or better and 20/20 or better and a
      DCNVA 20/40 or better and 20/25 or better were not statistically significant.
      CONCLUSIONS: Six months clinical outcome of cataract surgery with an AT-45 for
      the high myopic eyes was satisfactory; it was not significantly different from
      that of the non-high myopic eyes.

PMID- 18612225
TI  - Clinical outcomes of surgical techniques in congenital cataracts.
AB  - PURPOSE: To investigate the general clinical features of congenital cataracts and
      to determine their relationship to visual prognosis and surgical complications
      according to age at operation and surgical procedure adopted. METHOD: We
      retrospectively evaluated 92 eyes in 61 patients with congenital cataracts who
      underwent cataract surgery between January 1996 and December 2006. The
      demographic data, surgical technique, post-operative complications, and final
      visual prognosis were evaluated. RESULTS: The average age at surgery was 3.17
      years (range 1 month to 11 years), and the mean follow-up was 40.02 months (range
      6 to 46 months). Of the 56 eyes that could be checked for visual acuity after
      cataract extraction, 29 (51.7%) had a BCVA of > or = 0.5 at last visit.
      Unilateral congenital cataracts (p=0.025) and congenital cataracts with
      strabismus (p=0.019) showed significantly poorer visual outcomes. Patients with
      nystagmus also experienced a poor visual outcome; 6 patients (67%) had a BCVA of
      <0.1. Posterior cataracts had the worst visual prognosis (p=0.004). No
      statistically significant differences in posterior capsular opacity (p=0.901) or
      synechia formation (p=0.449) were observed between surgical techniques, but
      children younger than one year showed a higher tendency for PCO and synechia
      formation. CONCLUSIONS: Anterior vitrectomy did not reduce postoperative
      complications. Higher rates of complications (PCO, posterior synechia) developed
      in children younger than one year of age.

PMID- 18612226
TI  - The therapeutic effects of bevacizumab in patients with polypoidal choroidal
      vasculopathy.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab for
      polypoidal choroidal vasculopathy (PCV). METHODS: In this retrospective
      interventional pilot study, 12 eyes of 11 patients with active PCV were treated
      with intravitreal bevacizumab (1.25 mg) alone or in combination with photodynamic
      therapy (PDT) depending on the informed patient's choice. Intravitreal
      bevacizumab was repeated at 6-week intervals until the regression of active
      lesion was detected on fluorescein angiography (FA) which was done on a regular
      basis, Indocyanine green angiography (ICGA) and optical coherence tomography
      (OCT) analyses. RESULTS: Intravitreal bevacizumab was given alone in 8 eyes
      (Group 1) and in combination with PDT in 4 eyes (Group 2). Mean follow-up
      duration was 17 weeks in group 1 and 15 weeks in group 2 after bevacizumab
      treatment. The mean number of bevacizumab injections was 2.2 in group 1 and 2.5
      in group 2. Mean BCVA improved from 20/63 to 20/40 in group 1 and 20/63 to 20/32
      in group 2. Of all eyes, the BCVA improved by > or = 2 lines in seven (58%) eyes
      and resolution of fluid and hemorrhages in clinical examination, an absence of
      leakage on repeat FAs, or resolved pigment epithelial detachment (PED) and/or
      subretinal fluid (SRF) on OCT exam was confirmed in 10 (83%) eyes. Partial or
      complete regression of the polypoidal vessels and interconnecting vessels was
      reported for most cases at the last follow-up. No significant ocular or systemic
      side effects were observed in both groups. CONCLUSIONS: Short-term results
      indicate that intravitreal bevacizumab (1.25 mg) alone or in combination with PDT
      is well tolerated and associated with improvement in BCVA and reduced
      angiographic leakage in most patients. Further evaluation of intravitreal
      bevacizumab therapy for the treatment of PCV is warranted.

PMID- 18612227
TI  - Macular hole as a risk factor of choroidal detachment in rhegmatogenous retinal
      detachment.
AB  - PURPOSE: Choroidal detachment (CD) associated with rhegmatogenous retinal
      detachment (RRD) is a rare, but serious condition, which makes the prognosis
      worse. Previously reported risk factors for CD in RRD patients include high
      myopia, aphakia, pseudophakia, and advanced age. However, macular hole has not
      been discussed as an important factor in increasing the risk of CD in RRD
      patients. The purpose of this study was to evaluate macular hole as a risk factor
      for CD in eyes evidencing RRD. METHODS: The medical records of 480 patients with
      primary RRD were reviewed. We compared the CD incidence among the RRD patients in
      accordance with the presence or absence of macular holes. The relationship
      between gender, age, presence of systemic disease, refractive errors, lens
      status, intraocular pressure and the development of CD were also analyzed.
      RESULTS: The incidence (4/21 eyes, 19.0%) of CD in the RRD with macular hole was
      significantly higher than that (7/459 eyes, 1.5%) observed in the RRD without
      macular hole (p=0.010). The preoperative intraocular pressure (mean+/-SD; 2.5+/
      1.3 mmHg) in the RRD with CD and macular hole was significantly lower than that
      (7.4+/-4.4 mmHg) observed in the cases of RRD with CD without macular hole
      (p=0.035). The eyes complicated by CD evidenced a higher prevalence of diabetes
      mellitus (p=0.024) than was observed in the eyes without CD. CONCLUSIONS: The
      retinal detachment combined with macular hole creates a predisposition toward the
      development of profound hypotony and CD.

PMID- 18612228
TI  - Vertical rectus muscles transposition in large exotropia with medial rectus
      muscle transection following endoscopic sinus surgery.
AB  - PURPOSE: To evaluate the effect of transposition procedures on the vertical
      rectus muscle (VRM) in the patients who underwent a medial rectus muscle (MR)
      transection after endoscopic sinus surgery (ESS). METHODS: In 4 patients with
      exotropia (XT) and a lack of adduction after ESS, orbital CT or MRI revealed a
      complete transection of the midportion of the MR. Full-tendon VRM transposition
      was performed within 3 months after injury (early surgery) in 2 patients with 40
      delta XT. Two patients with 70 delta and 85 delta XT underwent an X-type
      augmented Hummelsheim procedure, which involved pulling each half-tendon and
      crossing it through the undersurface of the severed MR to the other end of the MR
      insertion, concurrently with an ipsilateral lateral rectus (LR) recession 11
      months and 36 months after ESS, respectively. The adduction deficits were divided
      into -1 through to -8. The patients were followed up for more than than 1.5
      years. RESULTS: Postoperatively, 3 patients showed orthophoria and no diplopia in
      the primary position. The adduction deficits improved to -3.5 or -4. One patient
      who underwent an X-type augmented Hummelsheim procedure showed a residual XT of
      25 delta. CONCLUSIONS: VRM transposition is effective in correcting a large XT
      secondary to a MR transection after ESS. When a longstanding large-angle XT with
      severe contracture of the ipsilateral LR and massive scarring of the adjacent
      tissues is present, the X-type augmented Hummelsheim procedure coupled with an
      ipsilateral LR recession had an augmenting effect.

PMID- 18612229
TI  - The Comparison of outcomes between lateral rectus muscles re-recession and medial
      rectus muscles resection in recurrent exotropia.
AB  - PURPOSE: To compare the surgical outcomes between bilateral lateral rectus
      muscles (BLR) re-recession and bilateral medial rectus muscles (BMR) resection in
      recurrent exotropia. METHODS: The medical records of patients with recurrent
      exotropia who underwent surgery for intermittent exotropia during the 6 years
      from January 2001 to December 2006 and followed up for more than 6 months were
      reviewed retrospectively. RESULTS: In group A, BLR recessions was performed at
      the first surgery and BLR re-recession was performed at the second surgery. In
      group B, BLR recession was performed at the first surgery and BMR resection at
      the second surgery. Success rates at the last follow-up after the second
      operation were 81.9% in Group A and 83.3% in Group B, showing no statistical
      difference between the two groups. In group A, no significant underaction of the
      BLR was noted. Success rates were not statistically different between the 2 mm re
      recessed subgroup and 3 mm re-recessed subgroup. CONCLUSIONS: The results support
      the notion that BLR re-recession successfully corrects recurrent exotropia
      without producing significant limitation of abduction.

PMID- 18612230
TI  - The effects of optic disc factors on retinal nerve fiber layer thickness
      measurement in children.
AB  - PURPOSE: We analyzed the effect of the changes of the optic disc area (ODA)
      caused by the axial length and the refractive error, and the consequent changes
      of the distance from the optic disc margin to the circular scan (OD-CS) of
      Optical coherence tomography (OCT) on the measurement of the retinal nerve fiber
      layer thickness(RNFLT) were examined. METHODS: One hundred two eyes of 51
      children (age range 4 to 15 years) were measured using OCT including the RNFLT.
      For the ODA and the OD-CS, the relative area formed by the ODA and the circular
      scan was obtained. In addition, the correlation of the refractive error and the
      axial length to the optic disc factors was assessed. RESULTS: As hyperopia
      progresses to myopia, the axial length became longer, the ODA became smaller (r=
      0.442, p=0.000) and the OD-CS showed a tendency to increase (r=0.471, p=0.000).
      As the OD-CS became longer, the measured average RNFLT decreased significantly
      (r=-0.248, p=0.012), and the ODA and the OD-CS showed a significant correlation
      to the RNFL thickness that was measured in the nasal and inferior areas, the S2,
      N2 and N3 areas and the I1 area. CONCLUSIONS: As ODA becomes smaller and the OD
      CS becomes longer, the RNFLT measured in the nasal and inferior areas, the S2,
      N2, N3, I1 area has a tendency to be thinner. Hence, consideration of the disc
      area is required when interpreting the RNFLT of these eyes.

PMID- 18612231
TI  - Short-term Efficacy of Topical Immunosuppressive Agents on the Survival of
      Cultivated Allo-Conjunctival Equivalents.
AB  - PURPOSE: To investigate the short-term efficacy of topical immunosuppressive
      agents on the survival of cultivated allo-conjunctival equivalents. METHODS:
      Twenty-five eyes of New Zealand white rabbits were included. Temporal
      conjunctivae were trephined to a diameter of 7.5 mm, and then cultured allo
      conjunctival epithelial cells on amniotic membrane were transplanted onto them.
      Various immunosuppressants including steroid, cyclosporine, and rapamycin were
      applied topically four times a day for a week. Epithelial defects and graft edema
      were graded daily. Numbers of inflammatory cells were measured in H&E. PKH26 and
      cytokeratin 4 and 7 were immunostained. RESULTS: Earlier epithelialization was
      observed in 1% steroid-treated eyes and defects persisted significantly in 0.5%
      CsA applied eyes. In histology, PKH26 positive cells considered as donor cells
      were only found in 1% steroid or 0.01% rapamycin applied eyes. 1% steroid- or
      0.01% rapamycin-applied eyes both showed positive staining for keratin-4 and -7.
      Inflammatory cells were less found in 1% steroid or 0.01% rapamycin treated eyes.
      CONCLUSIONS: Topical steroid or rapamycin can help to suppress acute inflammation
      and enhance the acute survival of transplanted conjunctival cells.

PMID- 18612232
TI  - Recurrent occlusion of laser iridotomy sites after posterior chamber phakic IOL
      implantation.
AB  - We report a case of recurrent occlusion of laser iridotomy (LI) sites after a
      Visian ICL (Implantable contact lens version 4, Staar Surgical AG, Nidau,
      Switzerland) implantation. A 45-year-old woman had bilateral ICL implantation
      after placement of two peripheral LI sites in each eye to prevent pupillary
      block. At one month after the operation, severe narrowing or occlusion of four LI
      sites occurred. After this, although she received four additional LIs at
      postoperative months 1, 6, 9 and 10 in both eyes, the narrowing or occlusion
      recurred. Mild chronic anterior chamber inflammation was observed intermittently
      throughout the follow-up period. We performed clear lens extraction in both eyes
      (at postoperative month 11 in the left eye and month 26 in the right eye) due to
      recurrent occlusion of the LI sites and excess trabecular meshwork pigment
      deposition presumably caused by the four repeated LIs. Recurrent obstruction of
      LI sites can occur after ICL implantation. These problems were unresolvable
      despite four repeated laser iridotomies. The risks associated with anterior
      uveitis must be considered when planning an ICL implantation.

PMID- 18612234
TI  - Reorganization of photoreceptor layer on optical coherence tomography concurrent
      with visual improvement after macular hole surgery.
AB  - To report three cases in which reorganization of the photoreceptor layer on
      optical coherence tomography (OCT) was concurrent with long-term visual recovery
      after macular hole surgery. Serial OCT scans of three eyes in which visual acuity
      continued to improve for 1 or more years after successful macular hole surgery
      were reviewed. Case 1. At postoperative four weeks, visual acuity was 20/100 with
      disorganized photoreceptor layer on OCT. The photoreceptor layer had been
      reorganized and visual acuity had improved to 20/25 by 1 year. Case 2. Two weeks
      after the operation, visual acuity was 20/125 and disorganization of the
      photoreceptor layer was noted. Visual acuity improved to 20/50 by four months.
      The photoreceptor layer had been partly reorganized and had appearance of a
      broken line. Visual acuity had improved to 20/40 and the photoreceptor layer had
      been reorganized further with a residual defect on OCT by 15 months. Case 3.
      Visual acuity at two weeks was 20/100. OCT revealed disorganization of the
      photoreceptor layer. Six months after the operation, the partly reorganized
      photoreceptor layer appeared as a broken line and visual acuity had reached
      20/80. Visual acuity had improved further to 20/40 by 1 year, concurrent with
      improved organization of the photoreceptor layer. The reorganization of the
      photoreceptor layer plays a part in long-term improvement of visual acuity after
      macular hole surgery.

PMID- 18612233
TI  - Choroidal ischemia and serous macular detachment associated with severe
      postoperative pain.
AB  - To report the association of a unilateral serous macular detachment with severe
      postoperative pain. A 71-year-old woman presented with a sudden decrease in
      vision in the right eye, seven days after a total knee replacement arthroplasty.
      The patient's history was unremarkable except for a severe pain greater than the
      visual analog scale of 8 points for about 2 days after surgery. Retinal
      examination showed a well differentiated serous detachment that was about 3.5
      disc diameter in size and located in the macular area. Fluorecein angiography and
      indocyanine green angiography showed delayed perfusion of the choriocapillaris
      without leakage points in the early phase and persistent hypofluorescence with
      pooling of dye in the subretinal space in the late phase. There was a spontaneous
      resolution of the serous detachment and the choroidal changes with residual
      pigment epithelial changes. Severe postoperative pain may influence the
      sympathetic activity and introduce an ischemic injury with a focal, choroidal
      vascular compromise and secondary dysfunction of overlying RPE cells in select
      patients.

PMID- 18612235
TI  - Cytomegalovirus retinitis after intravitreous triamcinolone injection in a
      patient with central retinal vein occlusion.
AB  - To report a case of cytomegalovirus (CMV) retinitis after intravitreal injection
      of triamcinolone acetonide (IVTA). A 77-year-old woman with macular edema due to
      central retinal vein occlusion (CRVO) developed peripheral retinitis 4 months
      after IVTA. A diagnostic anterior chamber paracentesis was performed to obtain
      DNA for a polymerase chain reaction (PCR) test for viral retinitis. The PCR test
      was positive for CMV DNA. Other tests for infective uveitis and immune competence
      were negative. Four months after presentation, gancyclovir was intravitreously
      injected a total of 5 times, and the retinitis resolved completely. CMV retinitis
      is a rare complication of local immunosuppression with IVTA. It can be managed
      with timely injection of intravitreal gancyclovir until recovery from local
      immunosuppression.

PMID- 18612236
TI  - Identification and localization of alpha-synuclein in human cornea.

PMID- 18612237
TI  - Fine mapping of the rice Bph1 gene, which confers resistance to the brown
      planthopper (Nilaparvata lugens stal), and development of STS markers for marker
      assisted selection.
AB  - The brown planthopper (BPH) is a major insect pest in rice, and damages these
      plants by sucking phloem-sap and transmitting viral diseases. Many BPH resistance
      genes have been identified in indica varieties and wild rice accessions, but none
      has yet been cloned. In the present study we report fine mapping of the region
      containing the Bph1 locus, which enabled us to perform marker-aided selection
      (MAS). We used 273 F8 recombinant inbred lines (RILs) derived from a cross
      between Cheongcheongbyeo, an indica type variety harboring Bph1 from Mudgo, and
      Hwayeongbyeo, a BPH susceptible japonica variety. By random amplification of
      polymorphic DNA (RAPD) analysis using 656 random 10-mer primers, three RAPD
      markers (OPH09, OPA10 and OPA15) linked to Bph1 were identified and converted to
      SCAR (sequence characterized amplified region) markers. These markers were found
      to be contained in two BAC clones derived from chromosome 12: OPH09 on
      OSJNBa0011B18, and both OPA10 and OPA15 on OSJNBa0040E10. By sequence analysis of
      ten additional BAC clones evenly distributed between OSJNBa0011B18 and
      OSJNBa0040E10, we developed 15 STS markers. Of these, pBPH4 and pBPH14 flanked
      Bph1 at distances of 0.2 cM and 0.8 cM, respectively. The STS markers pBPH9,
      pBPH19, pBPH20, and pBPH21 co-segregated with Bph1. These markers were shown to
      be very useful for marker-assisted selection (MAS) in breeding populations of 32
      F6 RILs from a cross between Andabyeo and IR71190, and 32 F5 RILs from a cross
      between Andabyeo and Suwon452.

PMID- 18612238
TI  - Thymidylate synthase and dihydropyrimidine dehydrogenase levels are associated
      with response to 5-fluorouracil in Caenorhabditis elegans.
AB  - 5-Fluorouracil (5-FU), a pyrimidine antagonist, has a long history in cancer
      treatment. The targeted pyrimidine biosynthesis pathway includes
      dihydropyrimidine dehydrogenase (DPD), which converts 5-FU to an inactive
      metabolite, and thymidylate synthase (TS), which is a major target of 5-FU. Using
      Caenorhabditis elegans as a model system to study the functional and resistance
      mechanisms of anti-cancer drugs, we examined these two genes in order to
      determine the extent of molecular conservation between C. elegans and humans.
      Overexpression of the worm DPD and TS homologs (DPYD-1 and Y110A7A.4,
      respectively) suppressed germ cell death following 5-FU exposure. In addition,
      DPYD-1 depletion by RNAi resulted in 5-FU sensitivity, while treatment with
      Y110A7A.4 RNAi and 5-FU resulted in similar patterns of embryonic death. Thus,
      the pathway of 5-FU function appears to be highly conserved between C. elegans
      and humans at the molecular level.

PMID- 18612239
TI  - Activation of small GTPases RhoA and Rac1 is required for avian reovirus p10
      induced syncytium formation.
AB  - The first ORF of the ARV S1133 S1 segment encodes the nonstructural protein p10,
      which is responsible for the induction of cell syncytium formation. However, p10
      dependent signaling during syncytium formation is fully unknown. Here, we show
      that dominant negative RhoA, Rho inhibitor C3 exoenzyme, ROCK/Rho-kinase
      inhibitor Y-27632 and Rac1 inhibitor NSC23766 inhibit p10-mediated cell fusion.
      p10 over-expression is concomitant with activation and membrane translocation of
      RhoA and Rac1, but not cdc42. RhoA and Rac1 downstream events, including JNK
      phosphorylation and transcription factor AP-1 and NF-kappaB activation, as well
      as MLC expression and phosphorylation are simultaneously activated by p10. p10
      point mutant T13M possessed 20% fusion-inducing ability and four p10 fusion
      deficient mutants V15M, V19M, C21S and L32A reduced or lost their ability to
      activate RhoA and Rac1 signaling. We conclude that p10-mediated syncytium
      formation proceeds by utilizing RhoA and Rac1-dependent signaling.

PMID- 18612240
TI  - Structural characterization of the genome of BERV gamma4, the most abundant
      endogenous retrovirus family in cattle.
AB  - The genome of replication-competent BERV gamma4 provirus, which is the most
      abundant ERV family in the bovine genome, was characterized in detail. The BERV
      gamma4 genome showed that BERV gamma4 harbors 8576 nucleotides and has the
      typical 5'-long terminal repeat (LTR)-gag-pro-pol-env-LTR-3' retroviral
      organization with a long leader region positioned before the gag open reading
      frame. Multiple sequences analysis showed that the nucleotide difference between
      5' and 3' LTRs was 4.2% (mean value 0.042) in average, suggesting that the
      provirus formed at most 13.3 million years ago. Gag separated by a stop codon
      from pro-pol in the same reading frame, while env resides in another reading
      frame lacking of a functional surface domain. According to the current bovine
      genome sequence assembly, the full-length BERV gamma4 provirus sequences were
      only found in the chromosomes 1, 2, 6, 10, 15, 23, 26, 28, X, and unassigned,
      although the partial sequences almost evenly distributed in the entire bovine
      genome. This is the first detailed study describing the genome structure of BERV
      gamma4, the most abundant ERV family present in bovine genome. Combined with our
      recent reports on characterization of ERVs in bovine, this study will contribute
      to illuminate ERVs in the cattle of which no information was previously
      available.

PMID- 18612241
TI  - Functional conservation and divergence of FVE genes that control flowering time
      and cold response in rice and Arabidopsis.
AB  - Recent molecular and genetic studies in rice, a short-day plant, have elucidated
      both conservation and divergence of photoperiod pathway genes and their
      regulators. However, the biological roles of rice genes that act within the
      autonomous pathway are still largely unknown. In order to better understand the
      function of the autonomous pathway genes in rice, we conducted molecular genetic
      analyses of OsFVE, a rice gene homologous to Arabidopsis FVE. OsFVE was found to
      be ubiquitously expressed in vegetative and reproductive organs. Overexpression
      of OsFVE could rescue the flowering time phenotype of the Arabidopsis fve mutants
      by up-regulating expression of the SUPPRESSOR OF OVEREXPRESSION OF CO1 (SOC1) and
      down-regulating FLOWERING LOCUS C (FLC) expression. These results suggest that
      there may be a conserved function between OsFVE and FVE in the control of
      flowering time. However, OsFVE overexpression in the fve mutants did not rescue
      the flowering time phenotype in in relation to the response to intermittent cold
      treatment.

PMID- 18612242
TI  - Characterization of a chalcosyltransferase (gerGTII) in dihydrochalcomycin
      biosynthesis.
AB  - An open reading frame, designated GerGTII and located downstream of the
      polyketide synthase genes, has been identified as a chalcosyltransferase by
      sequence analysis in the dihydrochalcomycin biosynthetic gene cluster of
      Streptomyces sp. KCTC 0041BP. The deduced product of gerGTII is similar to
      several glycosyltransferases, authentic and putative, and it displays a consensus
      sequence motif that appears to be characteristic of a sub-group of these enzymes.
      Specific disruption of gerGTII within the S. sp. KCTC 0041BP genome by
      insertional in-frame deletion method, resulted complete abolishment of
      dihydrochalcomycin and got the 20-O-mycinosyl-dihydrochalconolide as intermediate
      product in dihydrochalcomycin biosynthesis which was confirmed by electron spray
      ionization-mass spectrometry and liquid chromatography-mass spectrometry.
      Dihydrochalcomycin also was recovered after complementation of gerGTII.

PMID- 18612243
TI  - Lamin A/C and polymeric actin in genome organization.
AB  - In this work, we have studied the structural and functional linkage between lamin
      A/C, nuclear actin, and organization of chromosome territories (CTs) in mammary
      carcinoma MCF-7 cells. Selective down-regulation of lamin A/C expression led to
      disruption of the lamin A/C perinuclear layer and disorganization of lamin-bound
      emerin complexes at the inner nuclear membrane. The silencing of lamin A/C
      expression resulted in a decrease in the volume and surface area of chromosome
      territories, especially in chromosomes with high heterochromatin content.
      Inhibition of actin polymerization led to relaxation of the structure of
      chromosome territories, and an increase in the volumes and surface areas of the
      chromosome territories of human chromosomes 1, 2 and 13. The results show an
      important role of polymeric actin in the organization of the nuclei and the
      chromosome territories.

PMID- 18612244
TI  - Identification of a cryptic type III polyketide synthase (1,3,6,8
      tetrahydroxynaphthalene synthase) from Streptomyces peucetius ATCC 27952.
AB  - We identified a 1,134-bp putative type III polyketide synthase from the sequence
      analysis of Streptomyces peucetius ATCC 27952, named Sp-RppA, which is
      characterized as 1,3,6,8-tetrahydroxynaphthalene synthase and shares 33% identity
      with SCO1206 from S. coelicolor A3(2) and 32% identity with RppA from S. griseus.
      The 1,3,6,8-tetrahydroxynaphthalene synthase is known to catalyze the sequential
      decarboxylative condensation, intramolecular cyclization, and aromatization of an
      oligoketide derived from five units of malonyl-CoA to give 1,3,6,8
      tetrahydroxynaphthalene, which spontaneously oxidizes to form 2,5,7-trihydroxy
      1,4-naphthoquinone (flaviolin). In this study, we report the in vivo expression
      and in vitro synthesis of flaviolin from purified gene product (Sp-RppA).

PMID- 18612245
TI  - MMTS, a new subfamily of Tc1-like transposons.
AB  - A novel Tc1-like transposable element has been identified as a new DNA transposon
      in the mud loach, Misgurnus mizolepis. The M. mizolepis Tc1-like transposon
      (MMTS) is comprised of inverted terminal repeats and a single gene that codes Tc1
      like transposase. The deduced amino acid sequence of the transposase-encoding
      region of MMTS transposon contains motifs including DDE motif, which was
      previously recognized in other Tc1-like transposons. However, putative MMTS
      transposase has only 34-37% identity with well-known Tc1, PPTN, and S elements at
      the amino acid level. In dot-hybridization analysis used to measure the copy
      numbers of the MMTS transposon in genomes of the mud loach, it was shown that the
      MMTS transposon is present at about 3.36 x 104 copies per 2 x 109 bp, and
      accounts for approximately 0.027% of the mud loach genome. Here, we also describe
      novel MMTS-like transposons from the genomes of carp-like fishes, flatfish
      species, and cichlid fishes, which bear conserved inverted repeats flanking an
      apparently intact transposase gene. Additionally, BLAST searches and phylogenetic
      analysis indicated that MMTS-like transposons evolved uniquely in fishes, and
      comprise a new subfamily of Tc1-like transposons, with only modest similarity to
      Drosophila melanogaster (foldback element FB4, HB2, HB1), Xenopus laevis, Xenopus
      tropicalis, and Anopheles gambiae (Frisky).

PMID- 18612246
TI  - The photoreceptor populations in the retina of the greater horseshoe bat
      Rhinolophus ferrumequinum.
AB  - Recently, we reported the existence of AII "rod" amacrine cells in the retina of
      the greater horseshoe bat Rhinolophus ferrumequinum (Jeon et al., 2007). In order
      to enhance our understanding of bat vision, in the present study, we report on a
      quantitative analysis of cone and rod photoreceptors. The average cone density
      was 9,535 cells/mm2, giving a total number of cones of 33,538 cells/retina. The
      average rod density was 368,891 cells/mm2, giving a total number of rods of
      1,303,517 cells. On average, the total populations of rods were 97.49%, and cones
      were 2.51% of all the photoreceptors. Rod: cone ratios ranged from 33.85:1
      centrally to 42.26:1 peripherally, with a mean ratio of 38.96:1. The average
      regularity index of the cone mosaic in bat retina was 3.04. The present results
      confirm the greater horseshoe bat retina to be strongly rod-dominated. The rod
      dominated retina, with the existence of AII cells discovered in our previous
      study, strongly suggests that the greater horseshoe bat retina has a functional
      scotopic property of vision. However, the existence of cone cells also suggests
      that the bat retina has a functional photopic property of vision.

PMID- 18612247
TI  - Genetic screen for genes involved in Chk2 signaling in Drosophila.
AB  - Chk2 is a well characterized protein kinase with key roles in the DNA damage
      response. Chk2 is activated by phosphorylation following DNA damage, and relays
      that signal to various substrate proteins to induce cell cycle arrest, DNA
      repair, and apoptosis. In order to identify novel components of the Chk2
      signaling pathway in Drosophila, we screened 2,240 EP misexpression lines for
      dominant modifiers of an adult rough eye phenotype caused by Chk2 overexpression
      in postmitotic cells of the eye imaginal disc. The rough eye phenotype was
      suppressed by mutation of the ATM kinase, a well-described activator of Chk2.
      Twenty-five EP modifiers were identified (three enhancers and 22 suppressors),
      none of which correspond to previously known components of Chk2 signaling. Three
      EPs caused defects in G2 arrest after irradiation with incomplete penetrance when
      homozygous, and are likely directly involved in the response to DNA damage.
      Possible roles for these modifiers in the DNA damage response and Chk2 signaling
      are discussed.

PMID- 18612248
TI  - An adolescent male with features of EDNOS and obsessive-compulsive disorder.
AB  - OBJECTIVE: The current article describes the case of a 13-year-old boy with mixed
      diagnostic features suggestive of Eating Disorder Not Otherwise Specified (EDNOS)
      and obsessive-compulsive disorder. METHOD: A multimodal assessment approach was
      used to unravel the symptoms in this case. Initial presentation of the case had
      predominant features of EDNOS, however, obsessive-compulsive disorder features
      appeared to better explain disordered eating characteristics as the case
      progressed. In particular, the presence of intrusive images hindered his ability
      to consume food. RESULTS: A variety of psychological approaches, including
      components of family and cognitive-behavioral strategies had a slight impact on
      symptoms. Medication seemed to have a more substantial effect. CONCLUSION: This
      rather unique case, which contained features of EDNOS and obsessive compulsive
      disorder, illustrates the need for an ongoing multimodal assessment and
      interdisciplinary treatment approach.

PMID- 18612249
TI  - Disordered eating in men: a look at perceived stress and excessive exercise.
AB  - Although once considered a 'female' disorder, eating disorders are becoming more
      prevalent in males. As such, researchers are beginning to focus on factors that
      predict eating disturbances in males. Previous research has established a
      relation between eating disorders and stress and exercise dependence. However,
      few studies have examined the relation between the more common diagnosis of
      disordered eating and stress and exercise dependence, particularly in men. The
      purpose of the present study was to investigate the relation between disordered
      eating, stress, and exercise dependence in undergraduate male students.
      Implications for counseling men suffering from disordered eating will be
      discussed.

PMID- 18612250
TI  - Eating disorder age of onset in males: distribution and associated
      characteristics.
AB  - The objective of this study was to determine the distribution of age of onset of
      eating disorders in males as well as the relationship between age of onset and
      various clinical and demographic characteristics. The medical records of 70 males
      consecutively admitted to an inpatient eating disorders unit between June of 1992
      and June of 2002 were retrospectively reviewed. Age of onset did not
      significantly differ by admission diagnosis and appeared to have a single peak at
      about age 14. Inpatients with older ages of onset reported lower percentage of
      mean matched population weight (r=-0.35, p=0.005) and longer duration of illness
      (r=0.26, p=0.03) than inpatients with younger ages of onset. This study confirms
      the findings of previous investigations performed on female samples and also
      finds some unique aspects of males with eating disorders important to consider in
      prevention and treatment programs targeting male populations.

PMID- 18612251
TI  - Anorexia nervosa: a survival analysis.
AB  - BACKGROUND: There are numerous reports of the standardized mortality ratio (SMR)
      of anorexia nervosa (AN). However, the life expectancy of AN, has not been
      reported. OBJECTIVE: To estimate the average life expectancy of patients who are
      diagnosed with AN at various ages. METHODS: A survival analysis was performed
      using decision analysis software and mortality data for British Columbia, Canada
      from Statscan and the SMR for AN previously reported for British Columbia,
      Canada. RESULTS: The life expectancy of patients who are diagnosed with AN is
      displayed in Table 1 and Figure 2. For example, statistically, a woman who has
      had AN since 15 years of age is likely to live 25 years less than predicted for
      the normal population. DISCUSSION: Survival curves should be used to illustrate
      the loss of life in AN, to motivate patients and families, and to assist in legal
      arguments and requests for funding.

PMID- 18612252
TI  - Internal consistency and validity of the BITE for the screening of bulimia
      nervosa in university students, Colombia.
AB  - OBJECTIVE: To establish the validity and internal consistency of the bulimic
      investigatory test, Edinburgh (BITE) in a non-clinical population of university
      students in Colombia. METHODS: A validation study with a cross-sectional sampling
      was designed. Two-hundred and sixty-one students were evaluated independently and
      blindly with BITE and the Composite International Diagnostic Interview. Kuder
      Richardson's test, sensitivity, specificity, predictive values, likelihood
      values, Cohen kappa, area under the ROC curve for BITE's symptoms scale and
      Cronbach's alpha for severity scale were computed. RESULTS: The Kuder
      Richardson's test was 0.86, two factors were identified which explain the 22.68%
      and 7.12% of variance. Cronbach's alpha for severity scale was 0.52. Area under
      ROC curve was 0.9736. The best cutoff point was 11 with sensitivity of 94.59%,
      specificity of 91.52%, positive predictive value of 64.81%, negative predictive
      value of 99.03%; with a concordance of 0.7226. CONCLUSIONS: The BITE's symptom
      scale is useful in identifying clinically binge-eaters in university students.

PMID- 18612253
TI  - Psychopathology and treatment of night eating syndrome: a review.
AB  - The article reviews the international literature about psychopathological aspects
      and treatments of Night Eating Syndrome (NES). Studies were found using Medline;
      data from recent international books and conferences about ED are included, but
      single case descriptions are not included in the study. NES seems to be
      consistently related to mood disorders and anxiety. There is a low overlap
      between other eating disorders, including binge eating disorder (BED), and NES.
      The relationship between the syndrome and substance abuse is unclear and needs
      further study. Sleep architecture seems not to be severely altered among those
      with NES. A limited number of treatment studies for NES have been published or
      presented. Most of the literature focuses on pharmacological treatment, with
      fewer psychotherapeutic approaches reported at this time. Larger, multi-site
      treatment studies would serve to confirm the findings of this first wave of
      clinical trials.

PMID- 18612254
TI  - A 2-year longitudinal study of eating attitudes, BMI, perfectionism, asceticism
      and family climate in adolescent girls and their parents.
AB  - The aim of this longitudinal study of 383 Swedish adolescent girls (11 and 13
      years old at year 1) and their parents was to examine changes in eating attitudes
      over a two-year period, and to investigate the predictive value of eating
      attitudes, perfectionism, asceticism, family climate and body mass index (BMI)
      for the development of disturbed eating attitudes. The following self-report
      questionnaires were used: Children's Eating Attitudes test, Eating Attitudes
      Test, Eating Disorder Inventory for Children, Eating Disorder Inventory 2, I
      Think I Am and The Family Climate. The frequency of disturbed eating attitudes
      increased with increased age in the girls. Children's eating attitudes, higher
      BMI than peers, the girls rating of a less healthy relation to family and their
      fathers' eating attitudes at year 1 contributed most to the prediction of
      disturbed eating attitudes for the girls 2 years later. The results suggest that
      early signs of disturbed eating attitudes and higher BMI than peers may be
      important predictors for the development of more serious eating disturbances
      among adolescent girls.

PMID- 18612255
TI  - Comparison of eating disorders and body image disturbances between Eastern and
      Western countries.
AB  - Factors associated with the development of eating disorders in countries with non
      Western cultures have not been adequately investigated in relation to Westernized
      countries. We therefore studied 243 girls [age =16.5+/-1.2 (SD)], recruited from
      schools in India, Tibet, the US and France. They completed the Figure Rating
      Scale (FRS), the Eating Attitudes Test (EAT), and the Beck Depression Inventory
      (BDI). The Tibetan group had a lower body mass index (BMI) than the other groups
      (p<0.0001), which did not differ from each other. All groups differed
      significantly on socio-economic status (SES), with those living in India having
      the highest (p<0.0001). Prior to controlling for age, SES, and BMI, there were no
      significant differences on any psychological measure between the individual
      countries, or when collapsed by East vs. West. However, after controlling for the
      same covariates, the Tibetan group selected a significantly larger current
      (p<0.0001) and ideal body size (p=0.03), compared to all the other countries, and
      had more body image discrepancy than the American group (p=0.04). After
      controlling only for BMI, the girls from the East had a larger current and ideal,
      but no difference on body image discrepancy. Body image discrepancy scores were
      best predicted by EAT scores and BMI, accounting for 35% of the variance
      (p<0.0001). EAT scores themselves were best predicted by mother's education, BDI,
      body image discrepancy, and drug and tobacco use, accounting for 33% of the
      variance (p<0.0001). Unlike some other studies, we did not observe greater body
      image discrepancy and eating pathology in Western cultures, whether or not
      controlling for age, SES, and BMI. There were no differences in eating and
      depression pathology between those in the US, France, or India. Indeed, the
      Tibetans, after controlling for their low BMI and SES, had the greatest body
      image discrepancy.

PMID- 18612256
TI  - Treatment dropout in drug-addicted women: are eating disorders implicated?
AB  - A high prevalence of eating disorders among drug-addicted female patients has
      been noted, and it could be associated to psychopathological underlying factors.
      Our aim was to assess eating disorder traits in women approaching a residential
      program for drug addiction. We hypothesized that these traits would correlate to
      more general psychopathological factors, and would influence treatment relapse. A
      sample of 204 substance dependent women attending a residential treatment was
      screened for psychopathological indices, and follow-up data were obtained at the
      end of the treatment. Clients had a high risk for eating disorders (15%), and
      lifetime prevalence was even higher (20%). Disordered eating was associated to
      psychopathological distress, in particular harm avoidance resulted significantly
      lower (p=0.005), evoking higher unresponsiveness to danger. Drug addiction
      treatment outcome is associated to completion of defined programs, and eating
      disorder was a key covariable in determining treatment relapse or success
      (p=0.03). Clinicians should be aware of this potential co-morbidity, and
      concurrent treatments should be attempted, in order to prevent symptomatic
      shifting.

PMID- 18612257
TI  - Prediction of disturbed eating attitudes in adolescent girls: a 3-year
      longitudinal study of eating patterns, self-esteem and coping.
AB  - OBJECTIVE: The purpose was to examine the extent to which yearly assessments of
      eating patterns and attitudes, self-esteem and coping strategies over a 3-year
      period among adolescent girls predicted the degree of disturbed eating attitudes
      at the year 3-assessment. Our main hypothesis was that such attitudes year 3
      would be predicted by eating attitudes, restrained, emotional, and external
      eating behaviour, as well as by low self-esteem and coping by acting out or
      avoidance. METHOD: Three-hundred and seventy- eight Swedish adolescent girls were
      assessed once a year for three years. RESULTS: The results suggest that eating
      patterns and attitudes were the strongest predictors of disturbed eating
      attitudes year 3. Self-esteem and coping had a limited predictive value for
      eating attitudes year 3, and the effect of self-esteem appeared to be mediated by
      coping. DISCUSSION: The results suggest that early eating patterns (e.g., more
      disturbed eating attitudes and restrained eating behaviors) and attitudes are
      potentially important predictors for the development of more serious eating
      disturbances among adolescent girls.

PMID- 18612258
TI  - Effectiveness of Medifast supplements combined with obesity pharmacotherapy: a
      clinical program evaluation.
AB  - PURPOSE: To evaluate the long-term impact of Medifast meal-replacement
      supplements (MMRS) combined with appetite suppressant medication (ASM) among
      participants who received 52 weeks of treatment. METHODS: We conducted a
      systematic program evaluation of weight loss data from a medically-supervised
      weight control program combining the use of MMRS and ASM. Data were obtained and
      analyzed from 1,351 patient (BMI> or =25) medical charts who had participated for
      at least 12 weeks of treatment. Outcomes included weight loss (kg) and percent
      weight loss from baseline and at 12, 24, and 52 weeks. Both completers and
      intention-to-treat analyses were conducted. Completers' (i.e., those with
      complete data for 52 weeks) outcomes were evaluated after stratification for
      reported adherence to the MMRS and ASM. RESULTS: Participants who completed 52
      weeks of treatment experienced substantial weight losses at 12 (-9.4+/-5.7 kg),
      24 (-12.0+/-8.1 kg), and 52 weeks (-12.4+/-9.2 kg) and all measures were
      significantly different from baseline weight (p<0.001 for all contrasts) for both
      true completers (n=324) and for ITT analysis (n=1,351). Fifty percent of patients
      remained in the program at 24 weeks and nearly 25% were still participating at
      one year. CONCLUSIONS: This weight loss program using a combination of MMRS and
      ASM produced significant and sustained weight losses at 52 weeks. Results were
      better than those typically reported for obesity pharmacotherapy in both short-
      and long-term studies and also better than those reported for partial meal
      replacement programs. Program retention at one year was similar to that reported
      in many controlled drug trials and better than most commercial programs reported
      in the literature.

PMID- 18612259
TI  - Intervening with coaches to promote awareness and prevention of weight pressures
      in cheerleaders.
AB  - Research has found that athletes, particularly those involved in "aesthetically
      oriented" sports, experience significant pressures for thinness and are at
      increased risk for developing eating disorders. This study targeted cheerleading
      coaches as potential change agents by training them to recognize the symptoms of
      eating disorders and reduce the pressures for thinness among their squads.
      Cheerleading coaches at national or regional conferences attended an intervention
      workshop or a control workshop. Coaches who attended the intervention workshop
      received information regarding negative coaching behaviors, the symptoms of
      eating disorders, and ways to manage athletes with eating disorders. In addition,
      intervention coaches were encouraged to participate in six intervention
      strategies (e.g., reading materials, video, parent handouts, etc.) after
      attending the workshop. Eight months following the workshop, the coaches
      completed an assessment battery designed to test the effectiveness of the entire
      intervention. The results indicated that the intervention was successful in
      producing behavior changes in coaches. However, the intervention was less
      successful in producing long-term change in knowledge about eating disorders.
      These findings imply that interventions can be implemented by important adult
      figures (e.g., coaches, teachers) but the overall effectiveness of these
      interventions must be enhanced in order to have a significant and long-term
      impact.

PMID- 18612260
TI  - Beyond autophagy: the role of UVRAG in membrane trafficking.
AB  - Autophagy is a lysosome-directed membrane trafficking event for the degradation
      of cytoplasmic components, including organelles. The past few years have seen a
      great advance in our understanding of the cellular machinery of autophagosome
      biogenesis, the hallmark of autophagy. However, our global understanding of
      autophagosome maturity remains relatively poor and fragmented. The topological
      similarity of autophagosome and endosome delivery to lysosomes suggests that
      autophagic and endosomal maturation may have evolved to share associated
      machinery to promote the lysosomal delivery of their cargoes. We have recently
      discovered that UVRAG, originally identified as a Beclin 1-binding autophagy
      protein, appears to be an important factor in autophagic and endosomal
      trafficking through its interaction with the class C Vps tethering complex. Given
      the ability of UVRAG to bind Beclin 1 and the class C Vps complex in a
      genetically and functionally separable manner, it may serve as an important
      regulator for the spatial and/or temporal control of diverse cellular trafficking
      events. As more non-autophagic functions of UVRAG are unveiled, our understanding
      of seemingly different cellular processes may move a step further.

PMID- 18612261
TI  - Autophagy and aging: new lessons from progeroid mice.
AB  - It is widely-assumed that the autophagic activity of living cells decreases with
      age and probably contributes to the accumulation of damaged macromolecules and
      organelles during aging. Over the last few years, the study of segmental
      progeroid syndromes in which certain aspects of aging are manifested precociously
      or in exacerbated form, has increased our knowledge of the molecular basis of
      aging. We have recently reported the unexpected finding that distinct progeroid
      murine models exhibit an extensive basal activation of autophagy instead of the
      characteristic decline in this process occurring during normal aging. Further
      studies on Zmpste24-null progeroid mice, which are a reliable model of human
      Hutchinson-Gilford progeria, have revealed that the observed autophagic increase
      is associated with a series of metabolic alterations resembling those occurring
      under calorie restriction or in other situations reported to prolong lifespan.
      Here, we analyze these unexpected findings and discuss their possible
      implications for the development of premature aging.

PMID- 18612262
TI  - Protein misfolding and cardiac disease: establishing cause and effect.
AB  - Numerous neurodegenerative diseases are characterized by the accumulation of
      misfolded amyloidogenic proteins. Recent data indicate that a soluble pre-amyloid
      oligomer (PAO) may be the toxic entity in these diseases and the visible amyloid
      plaques, rather than causing the disease, may simply mark the terminal pathology.
      In prior studies, we observed PAO in the cardiomyocytes of many human heart
      failure samples. To test the hypothesis that cardiomyocyte-restricted expression
      of a known PAO is sufficient to cause heart failure, transgenic mice were created
      expressing polyglutamine repeats of 83 (PQ83) or 19 (PQ19). Long PQ repeats (>50)
      form PAOs and result in neurotoxicity in Huntington's disease, whereas shorter PQ
      repeats are benign. PQ83 expression caused the intracellular accumulation of PAOs
      and aggregates leading to cardiomyocyte death and heart failure. Evidence of
      increased autophagy and necrosis accompanied the PQ83 cardiomyocyte pathology.
      The data confirm that protein misfolding resulting in intracellular PAO
      accumulation is sufficient to cause cardiomyocyte death and heart failure.

PMID- 18612263
TI  - ENHANCE and ONTARGET.

PMID- 18612264
TI  - Treating postoperative pain. Just a matter of medication?

PMID- 18612265
TI  - Preload index and fluid responsiveness: different aspects of the new concept of
      functional hemodynamic monitoring.

PMID- 18612267
TI  - Transcutaneous carbon dioxide monitoring in spontaneously breathing, nonintubated
      patients in the early postoperative period.
AB  - BACKGROUND: The authors investigated the accuracy of transcutaneous capnometry
      (TcPCO(2)) in estimating arterial blood carbon dioxide partial pressure (PaCO(2))
      during spontaneous breathing in patients admitted to our surgical intensive care
      unit (ICU). METHODS: Serial TcPCO(2) and PaCO(2) measurements were taken in
      stable patients undergoing postoperative monitoring after major abdominal,
      vascular, or thoracic surgery. Patients were enrolled 12 hours after extubation.
      Exclusion criteria were pulmonary dysfunction, hemodynamic instability, or
      anemia. Linear regression, mixed models, and Bland-Altman analyses were used to
      compare accuracy and correlation between the two variables. Data are presented as
      means (95% confidence intervals). RESULTS: PaCO(2) values ranged between 26 mmHg
      and 52 mmHg. Mean values for TcPCO(2) and PaCO(2) were 35.3 (33.8-36.8) mmHg and
      39.2 (37.6-40.7) (P<0.001). Bland-Altman analysis showed a bias of -3.8 (-5.1
      2.5) mmHg with upper and lower limits of agreement of 5.6 (3.4-7.9) mmHg and 
      13.3 (-15.6 -11.1) mmHg, respectively. Thirty-one (55.4%) measurements disagreed
      by 3 mmHg or more. Linear mixed model analysis with adjustment for repeated
      measurements showed low correlation (r=0.63; P<0.0005). There were small but
      significant differences between patients in the correlation coefficient (P=0.04).
      CONCLUSION: TcPCO(2) showed moderate bias with wide limits of agreement when
      compared to PaCO(2) in our patients. The regression model showed low correlation
      of the measurements when adjusting for repeated measurements and between-subject
      variances. TcPCO(2) may not provide an accurate quantitative estimation of
      PaCO(2) in stable, spontaneously breathing, nonintubated patients in the early
      postoperative period.

PMID- 18612266
TI  - Negative words on surgical wards result in therapeutic failure of patient
      controlled analgesia and further release of cortisol after abdominal surgeries.
AB  - BACKGROUND: The perception of pain is germane to the environmental stimuli.
      Nurses on surgical wards are the main contributor in influencing patients'
      psychophysiological fettle. The aim of the study was to investigate the effect of
      different words, negative or positive, from nurses on postoperative pain therapy
      with patient-controlled analgesia (PCA). METHODS: 1500 ASA I-II patients, who
      underwent abdominal hysterectomy, were screened and 771 were randomized into one
      of four groups. In the no words group (NW, N.=35), no words was delivered. The
      positive (PW, N.=248), partially negative (NW1, N.=241) and totally negative
      (NW2, N.=247) groups received corresponding words when treating with morphine
      PCA, the words were given singly at the 3(rd), 6(th), 12(th), 18(th) h and
      repeatedly at the 3(rd) and 6(th) h, and each group was redivided into six
      subgroups according to varying time points. Pain intensity, morphine consumption,
      side effects, overall sedation and satisfaction scores were recorded and plasma
      cortisol was tested. RESULTS: A total of 614 patients completed the study.
      Negative words expressed significant influence on pain therapy at the 3(rd) and
      6(th) h after surgeries (P<0.01), and this effect was more convenient in
      repeatedly treated patients (P<0.001). Positive and the 12(th) and 18(th) h
      negative words displayed little role in pain management. Morphine consumption,
      side effects, satisfaction and cortisol level converted with the change of the
      pain intensity. No intergroup differences were observed in patients' overall
      conditions. CONCLUSION: Negative words on surgical wards influenced postoperative
      pain management at the earlier period of time after abdominal surgeries
      associated with the HPA axis activation.

PMID- 18612268
TI  - Management of anesthesia in awake craniotomy.
AB  - The awake craniotomy technique was originally introduced for the surgical
      treatment of epilepsy and has subsequently been used in patients undergoing
      surgical management of supratentorial tumors, arteriovenous malformation, deep
      brain stimulation, and mycotic aneurysms near critical brain regions. This
      surgical approach aims to maximize lesion resection while sparing important areas
      of the brain (motor, somatosensory, and language areas). Awake craniotomy offers
      great advantages with respect to patient outcome. In this type of procedure, the
      anesthetist's goal is to make the operation safe and effective and reduce the
      psychophysical distress of the patient. Many authors have described different
      anesthetic care protocols for awake craniotomy based on monitored or general
      anesthesia; however, there is still no consensus as to the best anesthetic
      technique. The most commonly used drugs for awake craniotomies are propofol and
      remifentanil, but dexmedetomidine is beginning to be used more commonly outside
      of Europe. Personal experience, careful planning, and attention to detail are the
      basis for obtaining good awake craniotomy RESULTS: Additional studies are
      necessary in order to optimize the procedure, reduce complications, and improve
      patient tolerance. The aim of this review is to present a thorough report of the
      literature, with particular attention to neuro-oncology surgery.

PMID- 18612269
TI  - Hyperhomocysteinemia, antithrombin consumption, and early venous graft closure in
      surgical coronary revascularization.
AB  - Hyperhomocysteinemia is a pathological condition that increases cardiovascular
      risk due to prothrombotic behaviour in the patient. This case report concerns a
      61-year-old man undergoing surgical coronary revascularization for early
      thrombosis of the venous graft. The postoperative antithrombin activity was
      extremely low (33%), despite normal preoperative values (79%) and a short
      cardiopulmonary bypass. At a subsequent screening, the patient was diagnosed with
      hyperhomocysteinemia (18.4 mmol/L) due to a heterozygous C677T mutation of the
      enzyme methylenetetrahydrofolate reductase associated with a folate deficiency.
      Hyperhomocysteinemia and cardiac operation are both factors that induce increased
      thrombin formation, which may induce antithrombin consumption and a consequent
      thrombotic event. Further studies are needed to define hyperhomocysteinemia as an
      independent risk factor for thrombotic events after cardiac surgery.

PMID- 18612270
TI  - Serotonin syndrome caused by olanzapine and clomipramine.

PMID- 18612272
TI  - The other path for follow-ons.
AB  - With follow-on biologics essentially dead in the water in the US, the decision of
      the world's largest generics manufacturer to invest in a platform for enhancing
      protein pharmacokinetics could pay dividends.

PMID- 18612271
TI  - The immunogenicity of adenovirus vectors limits the multispecificity of CD8 T
      cell responses to vector-encoded transgenic antigens.
AB  - We investigated whether the immunogenicity of antigens delivered by recombinant
      E1-deleted adenovirus (Ad) is impaired by the concomitant priming of specific
      immunity to protein antigens of the vector. A comparative evaluation of the
      immunogenicity of hepatitis B surface antigen (HBsAg or S) or ovalbumin (OVA) was
      carried out in mice injected with either the antigen-encoding Ad vector or a
      corresponding plasmid DNA vaccine. Recombinant Ad, but not the plasmid DNA
      vaccine, induced long lasting, specific CD8 T-cell immunity to immunodominant
      epitopes of the two antigens. In contrast, the HBsAg-encoding pCI/S DNA, but not
      the Ad/S vaccine, was shown to prime CD8 T-cell responses to subdominant HBsAg
      epitopes. Ad/S-primed CD8 T-cell responses to immunodominant epitopes of vector
      encoded or capsid-delivered Ad proteins apparently suppressed CD8 T-cell priming
      to subdominant HBsAg epitopes. In B-cell-deficient mice, the established, Ad
      specific T-cell immunity induced by vaccination with an irrelevant Ad vector
      impaired the priming of HBsAg-specific CD8 T-cell responses by Ad/S. It is clear,
      therefore, that a T-cell immunity specific for Ad proteins (either delivered with
      the Ad capsid or transcribed from the Ad genome) is efficiently primed by
      vaccination with Ad vectors, and can limit the immunogenicity (particularly of
      subdominant epitopes) of Ad vector-encoded transgenic antigens.

PMID- 18612273
TI  - In need of counseling?
AB  - Moves to clamp down on companies offering direct-to-consumer genetic tests are
      out of step with personal genomics and its potential to empower individuals' role
      in their own healthcare.

PMID- 18612274
TI  - 2 billion euro IMI launched with European pharma.

PMID- 18612275
TI  - Dyax backs albumin.

PMID- 18612276
TI  - Commercial interest waxes for IGF-1 blockers.

PMID- 18612277
TI  - Tighter gene tests.

PMID- 18612278
TI  - UK passes hybrids.

PMID- 18612279
TI  - Meta-analysis torpedoes blood substitutes.

PMID- 18612280
TI  - 50 cancers to be sequenced.

PMID- 18612281
TI  - Biofuels, take two.

PMID- 18612282
TI  - Pfizer jettisons Esperion.

PMID- 18612283
TI  - Pan-EU Biobanks.

PMID- 18612284
TI  - Genetically modified mosquitoes.

PMID- 18612285
TI  - Profile: Julian Davies.

PMID- 18612287
TI  - Poised to branch out.

PMID- 18612288
TI  - Europe to ban direct-to-consumer genetic tests?

PMID- 18612289
TI  - Dichotomies between computational and mathematical models.

PMID- 18612291
TI  - HLA-haplotype banking and iPS cells.

PMID- 18612292
TI  - Global mRNA changes in microarray experiments.

PMID- 18612293
TI  - (Re)defining biopharmaceutical.
AB  - Vested interests are redefining, rebranding and co-opting what is
      'biopharmaceutical'. This is not just a matter of semantics-the core identity of
      the biotech industry and its products is at stake.

PMID- 18612294
TI  - Public biotech 2007--the numbers.
AB  - Record profits and financing in the public biotech sector may be unsustainable in
      the coming years as economies falter.

PMID- 18612295
TI  - How many patents does a biopharmaceutical company need?
AB  - Young biotech companies may not need extensive patent portfolios to survive or
      grow.

PMID- 18612297
TI  - Hitting the mother lode of tumor angiogenesis.

PMID- 18612298
TI  - Setting the standard in synthetic biology.

PMID- 18612299
TI  - The long and short of carbon nanotube toxicity.

PMID- 18612302
TI  - Refinement and standardization of synthetic biological parts and devices.
AB  - The ability to quickly and reliably engineer many-component systems from
      libraries of standard interchangeable parts is one hallmark of modern
      technologies. Whether the apparent complexity of living systems will permit
      biological engineers to develop similar capabilities is a pressing research
      question. We propose to adapt existing frameworks for describing engineered
      devices to biological objects in order to (i) direct the refinement and use of
      biological 'parts' and 'devices', (ii) support research on enabling reliable
      composition of standard biological parts and (iii) facilitate the development of
      abstraction hierarchies that simplify biological engineering. We use the
      resulting framework to describe one engineered biological device, a genetically
      encoded cell-cell communication receiver named BBa_F2620. The description of the
      receiver is summarized via a 'datasheet' similar to those widely used in
      engineering. The process of refinement and characterization leading to the
      BBa_F2620 datasheet may serve as a starting template for producing many
      standardized genetically encoded objects.

PMID- 18612301
TI  - A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome
      analysis.
AB  - DNA methylation is an indispensible epigenetic modification required for
      regulating the expression of mammalian genomes. Immunoprecipitation-based methods
      for DNA methylome analysis are rapidly shifting the bottleneck in this field from
      data generation to data analysis, necessitating the development of better
      analytical tools. In particular, an inability to estimate absolute methylation
      levels remains a major analytical difficulty associated with immunoprecipitation
      based DNA methylation profiling. To address this issue, we developed a cross
      platform algorithm-Bayesian tool for methylation analysis (Batman)-for analyzing
      methylated DNA immunoprecipitation (MeDIP) profiles generated using
      oligonucleotide arrays (MeDIP-chip) or next-generation sequencing (MeDIP-seq). We
      developed the latter approach to provide a high-resolution whole-genome DNA
      methylation profile (DNA methylome) of a mammalian genome. Strong correlation of
      our data, obtained using mature human spermatozoa, with those obtained using
      bisulfite sequencing suggest that combining MeDIP-seq or MeDIP-chip with Batman
      provides a robust, quantitative and cost-effective functional genomic strategy
      for elucidating the function of DNA methylation.

PMID- 18612310
TI  - Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple
      negative immunophenotype.
AB  - Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of
      caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane
      involved in vesicular trafficking and signal transduction. Over the recent years
      there has been controversy about their role in breast cancer and their
      suitability as markers of basal-like phenotype. Caveolin-1 and CAV2 protein
      expression was assessed on a tissue microarray containing 880 unselected invasive
      breast cancer cases, by means of immunohistochemistry. Caveolin-1 and CAV2
      expression was observed in 13.4 and 5.9% of all breast cancer, respectively.
      Their expression was strongly associated with high histological grade, lack of
      steroid hormone receptor positivity (ER and PR), and expression of basal markers
      (basal cytokeratins, P63, P-cadherin). Furthermore, there was a significant
      association between CAV1 and CAV2 expression and basal-like phenotype. On
      univariate analysis only CAV2 had a prognostic impact on breast cancer-specific
      survival; however, this was not independent from other traditional markers on
      multivariate analysis. Our results demonstrate that both CAV1 and CAV2 are
      associated with basal-like phenotype. Further studies are warranted to determine
      whether they play an oncogenic role in basal-like/triple-negative breast cancer
      development or are just surrogate markers for this subgroup.

PMID- 18612311
TI  - Health and economic impact of HPV 16 and 18 vaccination and cervical cancer
      screening in India.
AB  - Cervical cancer is a leading cause of cancer death among women in low-income
      countries, with approximately 25% of cases worldwide occurring in India. We
      estimated the potential health and economic impact of different cervical cancer
      prevention strategies. After empirically calibrating a cervical cancer model to
      country-specific epidemiologic data, we projected cancer incidence, life
      expectancy, and lifetime costs (I$2005), and calculated incremental cost
      effectiveness ratios (I$/YLS) for the following strategies: pre-adolescent
      vaccination of girls before age 12, screening of women over age 30, and combined
      vaccination and screening. Screening differed by test (cytology, visual
      inspection, HPV DNA testing), number of clinical visits (1, 2 or 3), frequency (1
      x , 2 x , 3 x per lifetime), and age range (35-45). Vaccine efficacy, coverage,
      and costs were varied in sensitivity analyses. Assuming 70% coverage, mean
      reduction in lifetime cancer risk was 44% (range, 28-57%) with HPV 16,18
      vaccination alone, and 21-33% with screening three times per lifetime. Combining
      vaccination and screening three times per lifetime provided a mean reduction of
      56% (vaccination plus 3-visit conventional cytology) to 63% (vaccination plus 2
      visit HPV DNA testing). At a cost per vaccinated girl of I$10 (per dose cost of
      $2), pre-adolescent vaccination followed by screening three times per lifetime
      using either VIA or HPV DNA testing, would be considered cost-effective using the
      country's per capita gross domestic product (I$3452) as a threshold. In India, if
      high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides
      long-term protection is achievable, vaccination followed by screening three times
      per lifetime is expected to reduce cancer deaths by half, and be cost-effective.

PMID- 18612309
TI  - The contribution of large genomic deletions at the CDKN2A locus to the burden of
      familial melanoma.
AB  - Mutations in two genes encoding cell cycle regulatory proteins have been shown to
      cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone
      families bear a point mutation in the CDKN2A locus at 9p21, which encodes two
      unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also
      been linked to the disease. Although the CDKN2A gene has been shown to be the
      major melanoma predisposing gene, there remains a significant proportion of
      melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not
      been identified through direct exon sequencing. The purpose of this study was to
      assess the contribution of large rearrangements in CDKN2A to the disease in
      melanoma-prone families using multiplex ligation-dependent probe amplification.
      We examined 214 patients from independent pedigrees with at least two CMM cases.
      All had been tested for CDKN2A and CDK4 point mutation, and 47 were found
      positive. Among the remaining 167 negative patients, one carried a novel genomic
      deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total
      mutations in this series (1 of 48), confirming that they explain a very small
      proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21,
      KLHL9, as being a major CMM gene.

PMID- 18612312
TI  - Relationship between human tumour angiogenic profile and combretastatin-induced
      vascular shutdown: an exploratory study.
AB  - Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour
      vasculature. We investigated whether histological angiogenic profile can explain
      the differential sensitivity of human tumours to CA4P, by correlating the kinetic
      changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour
      immunohistochemical angiogenic markers. Tissue was received from 24 patients
      (mean age 59, range 32-73, 18 women, 6 men). An angiogenic profile was performed
      using standard immunohistochemical techniques. Dynamic MRI data were obtained for
      the same patients before and 4 h after CA4P. Three patients showed a
      statistically significant fall in K(trans) following CA4P, and one a
      statistically significant fall in IAUGC(60). No statistically significant
      correlations were seen between the continuous or categorical variables and the
      DCE-MRI kinetic parameters other than between ang-2 and K(trans) (P=0.044). In
      conclusion, we found no strong relationships between changes in DCE-MRI kinetic
      variables following CA4P and the immunohistochemical angiogenic profile.

PMID- 18612313
TI  - Therapeutic choices in patients with Ph-positive CML living in Mexico in the
      tyrosine kinase inhibitor era: SCT or TKIs?
AB  - A total of 72 patients with Ph-positive CML in first chronic phase were followed
      during a 6-year period in two different institutions in Mexico. Among them, 22
      were given a reduced-intensity allogeneic SCT, whereas 50 were given a tyrosine
      kinase inhibitor (TKI), mainly imatinib mesylate. The 6-year overall survival
      (OS) after the therapeutic intervention for patients allografted or given a TKI
      was 77 and 84%, respectively (P, NS); the median OS for both groups has not been
      reached, being above 90 and 71 months, respectively (P, NS). The freedom from
      progression to blast or accelerated phases was also similar for both groups, as
      well as the overall OS after diagnosis. Most patients allografted (91%) chose
      this treatment because they were unable to afford continuing treatment with the
      TKI, whereas most treated with the TKI (84%) were given the treatment without
      charge, through institutions able to pay for their treatment. The median cost of
      each nonmyeloablative allograft was US$18,000, an amount that is enough to cover
      180 days of treatment with imatinib (400 mg per day) in Mexico. Cost
      considerations favor allogeneic SCT as a 'once only' procedure whereas lifelong
      treatment with an expensive drug represents an excessive burden on resources.

PMID- 18612314
TI  - Transcriptomic screening of microvascular endothelial cells implicates novel
      molecular regulators of vascular dysfunction after spinal cord injury.
AB  - Microvascular dysfunction is a critical pathology that underlies the evolution of
      secondary injury mechanisms after traumatic spinal cord injury (SCI). However,
      little is known of the molecular regulation of endothelial cell (EC) plasticity
      observed acutely after injury. One reason for this is the relative lack of
      methods to quickly and efficiently obtain highly enriched spinal microvascular
      ECs for high-throughput molecular and biochemical analyses. Adult C57Bl/6 mice
      received an intravenous injection of fluorescein isothiocyanate (FITC)-conjugated
      Lycopersicon esculentum lectin, and FITC-lectin-bound spinal microvessels were
      greatly enriched by fluorescence-activated cell sorter (FACS) purification. This
      technique allows for rapid (<1.5 h postmortem) isolation of spinal cord
      microvascular ECs (smvECs). The results from cell counting, reverse-transcription
      polymerase chain reaction (RT-PCR), and western blot analyses show a high degree
      of EC enrichment at mRNA and protein levels. Furthermore, a focused EC biology
      microarray analysis identified multiple mRNAs dramatically increased in the EC
      compartment 24 h after SCI, which is a time point associated with the pathologic
      loss of spinal vasculature. These included thrombospondin-1, CCL5/RANTES, and
      urokinase plasminogen activator, suggesting they may represent targets for
      therapeutic intervention. Furthermore, these novel methodologic approaches will
      likely facilitate the discovery of molecular regulators of endothelial
      dysfunction in a variety of central nervous system (CNS) disorders including
      stroke and other neurodegenerative diseases having a vascular component.

PMID- 18612315
TI  - Roscovitine reduces neuronal loss, glial activation, and neurologic deficits
      after brain trauma.
AB  - Traumatic brain injury (TBI) causes both direct and delayed tissue damage. The
      latter is associated with secondary biochemical changes such as cell cycle
      activation, which leads to neuronal death, inflammation, and glial scarring.
      Flavopiridol--a cyclin-dependent kinase (CDK) inhibitor that is neither specific
      nor selective--is neuroprotective. To examine the role of more specific CDK
      inhibitors as potential neuroprotective agents, we studied the effects of
      roscovitine in TBI. Central administration of roscovitine 30 mins after injury
      resulted in significantly decreased lesion volume, as well as improved motor and
      cognitive recovery. Roscovitine attenuated neuronal death and inhibited
      activation of cell cycle pathways in neurons after TBI, as indicated by
      attenuated cyclin G1 accumulation and phosphorylation of retinoblastoma protein.
      Treatment also decreased microglial activation after TBI, as reflected by
      reductions in ED1, galectin-3, p22(PHOX), and Iba-1 levels, and attenuated
      astrogliosis, as shown by decreased accumulation of glial fibrillary acidic
      protein. In primary cortical microglia and neuronal cultures, roscovitine and
      other selective CDK inhibitors attenuated neuronal cell death, as well as
      decreasing microglial activation and microglial-dependent neurotoxicity. These
      data support a multifactorial neuroprotective effect of cell cycle inhibition
      after TBI--likely related to inhibition of neuronal apoptosis, microglial-induced
      inflammation, and gliosis--and suggest that multiple CDKs are potentially
      involved in this process.

PMID- 18612316
TI  - Metabolic challenge to glia activates an adenosine-mediated safety mechanism that
      promotes neuronal survival by delaying the onset of spreading depression waves.
AB  - In a model of glial-specific chemical anoxia, we have examined how astrocytes
      influence both synaptic transmission and the viability of hippocampal pyramidal
      neurons. This relationship was assessed using electrophysiological,
      pharmacological, and biochemical techniques in rat slices and cell cultures, and
      oxidative metabolism was selectively impaired in glial cells by exposure to the
      mitochondrial gliotoxin, fluoroacetate. We found that synaptic transmission was
      blocked shortly after inducing glial metabolic stress and peri-infarct-like
      spreading depression (SD) waves developed within 1 to 2 h of treatment. Neuronal
      electrogenesis was not affected until SD waves developed, thereafter decaying
      irreversibly. The blockage of synaptic transmission was totally reversed by A(1)
      adenosine receptor antagonists, unlike the development of SD waves, which
      appeared earlier under these conditions. Such blockage led to a marked reduction
      in the electrical viability of pyramidal neurons 1 h after gliotoxin treatment.
      Cell culture experiments confirmed that astrocytes indeed release adenosine. We
      interpret this early glial response as a novel safety mechanism that allocates
      metabolic resources to vital processes when the glia itself sense an energy
      shortage, thereby delaying or preventing entry into massive lethal ischemic-like
      depolarization. The implication of these results on the functional recovery of
      the penumbra regions after ischemic insults is discussed.

PMID- 18612317
TI  - Estradiol attenuates neuroprotective benefits of isoflurane preconditioning in
      ischemic mouse brain.
AB  - Isoflurane preconditioning (IsoPC) neuroprotection in experimental stroke is male
      specific. We determined whether estradiol alters ischemic outcomes in IsoPC brain
      and examined the role of estrogen receptors (ERs). Seven to 10 days before
      preconditioning, ovariectomized (OVX) mice were implanted with estradiol,
      vehicle, or ER subtype agonists. OVX+/-estradiol, OVX+/-vehicle, OVX+/-ER
      agonists, and ER subtype wild-type (WT) and knockout (KO) mice were
      preconditioned for 4 h with sham anesthetic preconditioning (sham PC) or 1% IsoPC
      and recovered for 24 h. Mice then underwent 2 h of middle cerebral artery
      occlusion followed by 22 h of reperfusion. Infarct volumes were determined by
      2,3,5-triphenyltetrazolium chloride staining, with comparisons between IsoPC and
      corresponding sham PC for each treatment group. Decreased infarct injury was seen
      in IsoPC OVX+/-vehicle, whereas estradiol in IsoPC OVX mice enhanced ischemic
      damage. In ER studies, increased infarct volumes were seen in IsoPC ERWT mice
      regardless of ER subtype. IsoPC in ERalphaKO mice had no effect on infarction
      volume but reduced only cortical ischemic damage in ERbetaKO mice. In OVX+ERalpha
      agonist, IsoPC had no effect on infarction volume. In OVX+ERbeta agonist, IsoPC
      increased cortical infarct volume. Estradiol depresses the brain's protective
      response to IsoPC and may exacerbate cortical ischemic injury mainly through an
      ERbeta-dependent mechanism.

PMID- 18612318
TI  - Circulating endothelial progenitor cells as a pathogenetic marker of moyamoya
      disease.
AB  - Moyamoya disease (MMD) is an unusual form of chronic cerebrovascular occlusive
      disease that involves the formation of characteristically abnormal vessels.
      Recent studies have reported that colony-forming unit (CFU) and outgrowth cells
      represent a subpopulation of endothelial progenitor cells (EPCs). Here, we
      attempted to determine the significance of CFU number and outgrowth cell yield in
      MMD. Endothelial progenitor cells were isolated from the blood of 24 adult MMD
      patients and from 48 age- and risk factor-matched control subjects. After 7 days
      of culture, CFUs were determined, and yields of outgrowth cells were measured
      during 2 months of culture. The EPC function was also evaluated using matrigel
      plate assays. It was found that CFU numbers were significantly lower in MMD
      patients than in controls. Moreover, during long-term culture, outgrowth cells
      were isolated from only 10% of control subjects but from 33% of MMD patients, and
      CFU numbers and tube formation were found to be lower in advanced MMD cases than
      in those with early stage disease, whereas outgrowth cells were more frequently
      detected in those with early MMD and moyamoya vessels than in those with advanced
      disease. These characteristics of circulating EPCs reflect mixed conditions of
      vascular occlusion and abnormal vasculogenesis during the pathogenesis of MMD.

PMID- 18612319
TI  - L-Arginine decreases fluid-percussion injury-induced neuronal nitrotyrosine
      immunoreactivity in rats.
AB  - Peroxynitrite is a powerful oxidant capable of nitrating phenolic moieties, such
      as tyrosine or tyrosine residues in proteins and increases after traumatic brain
      injury (TBI). First, we tested the hypothesis that TBI increases nitrotyrosine
      (NT) immunoreactivity in the brain by measuring the number of NT-immunoreactive
      neurons in the cerebral cortex and hippocampus of rats subjected to parasagittal
      fluid-percussion TBI. Second, we tested the hypothesis that treatment with L
      arginine, a substrate for nitric oxide synthase, further increases NT
      immunoreactivity over TBI alone. Rats were anesthetized with isoflurane and
      subjected to TBI, sham TBI, or TBI followed by treatment with L-arginine (100
      mg/kg). Twelve, 24, or 72 h after TBI, brains were harvested. Coronal sections
      (10 microm) were incubated overnight with rabbit polyclonal anti-NT antibody,
      rinsed, and incubated with a biotinylated secondary antibody. The antigen
      antibody complex was visualized using a peroxidase-conjugated system with
      diaminobenzidine as the chromagen. The number of NT-positive cortical and
      hippocampal neurons increased significantly in both ipsilateral and contralateral
      hemispheres up to 72 h after TBI compared with the sham-injured group.
      Remarkably, treatment with L-arginine reduced the number of NT-positive neurons
      after TBI in both cortex and hippocampus. Our results indicate that L-arginine
      actually prevents TBI-induced increases in NT immunoreactivity.

PMID- 18612321
TI  - Evolution of the mitochondrial genome of Metazoa as exemplified by comparison of
      congeneric species.
AB  - The mitochondrial genome (mtDNA) of Metazoa is a good model system for
      evolutionary genomic studies and the availability of more than 1000 sequences
      provides an almost unique opportunity to decode the mechanisms of genome
      evolution over a large phylogenetic range. In this paper, we review several
      structural features of the metazoan mtDNA, such as gene content, genome size,
      genome architecture and the new parameter of gene strand asymmetry in a
      phylogenetic framework. The data reviewed here show that: (1) the plasticity of
      Metazoa mtDNA is higher than previously thought and mainly due to variation in
      number and location of tRNA genes; (2) an exceptional trend towards stabilization
      of genomic features occurred in deuterostomes and was exacerbated in vertebrates,
      where gene content, genome architecture and gene strand asymmetry are almost
      invariant. Only tunicates exhibit a very high degree of genome variability
      comparable to that found outside deuterostomes. In order to analyse the genomic
      evolutionary process at short evolutionary distances, we have also compared
      mtDNAs of species belonging to the same genus: the variability observed in
      congeneric species significantly recapitulates the evolutionary dynamics observed
      at higher taxonomic ranks, especially for taxa showing high levels of genome
      plasticity and/or fast nucleotide substitution rates. Thus, the analysis of
      congeneric species promises to be a valuable approach for the assessment of the
      mtDNA evolutionary trend in poorly or not yet sampled metazoan groups.

PMID- 18612322
TI  - A nonlinear mixed-effect mixture model for functional mapping of dynamic traits.
AB  - Functional mapping has emerged as a next-generation statistical tool for mapping
      quantitative trait loci (QTL) that affect complex dynamic traits. In this
      article, we incorporated the idea of nonlinear mixed-effect (NLME) models into
      the mixture-based framework of functional mapping, aimed to generalize the
      spectrum of applications for functional mapping. NLME-based functional mapping,
      implemented with the linearization algorithm based on the first-order Taylor
      expansion, can provide reasonable estimates of QTL genotypic-specific curve
      parameters (fixed effect) and the between-individual variation of these
      parameters (random effect). Results from simulation studies suggest that the NLME
      based model is more general than traditional functional mapping. The new model
      can be useful for the identification of the ontogenetic patterns of QTL genetic
      effects during time course.

PMID- 18612323
TI  - Familial aggregation of preeclampsia and intrauterine growth restriction in a
      genetically isolated population in The Netherlands.
AB  - Preeclampsia and intrauterine growth restriction are related, pregnancy-specific
      disorders with a substantial genetic influence, which may have a joint genetic
      aetiology. We investigated familial aggregation, consanguinity and parent-of
      origin effects for preeclampsia and IUGR. Fifty women with previous preeclampsia
      and 56 with previous pregnancies complicated by intrauterine growth restriction
      were recruited from a recent genetically isolated population in the Netherlands.
      Their relationships were estimated by means of a large genealogy database that
      contains information on more than 110 000 individuals from the isolate over 23
      generations. Relationships were quantified using kinship and inbreeding
      coefficients. Parent-of-origin effects were evaluated by comparing parental
      kinships. Eighty-six women (39 preeclampsia and 47 intrauterine growth
      restriction) could be linked to one common ancestor within 14 generations. The
      proportion of related women with previous preeclampsia (95.6%) or pregnancies
      complicated by intrauterine growth restriction (95.1%) was significantly greater
      than expected by chance (P<0.001). Combined analysis of both disorders did not
      change the magnitude of familial aggregation. The proportion of women born from
      consanguineous marriages was increased in women with previous preeclampsia
      (81.8%) and those with intrauterine growth restriction (78%) compared to a random
      sample (P<0.001). Maternal and paternal kinships were not significantly different
      in both disorders. We demonstrate cosegregation of preeclampsia and intrauterine
      growth restriction, supporting a common genetic aetiology. The high proportion of
      parental consanguineous marriages suggests the possibility of an underlying
      recessive mutation. No evidence was found for a parent-of-origin effect either in
      preeclampsia or in intrauterine growth restriction.

PMID- 18612320
TI  - Shaping cups into phagosomes and macropinosomes.
AB  - The ingestion of particles or cells by phagocytosis and of fluids by
      macropinocytosis requires the formation of large endocytic vacuolar compartments
      inside cells by the organized movements of membranes and the actin cytoskeleton.
      Fc-receptor-mediated phagocytosis is guided by the zipper-like progression of
      local, receptor-initiated responses that conform to particle geometry. By
      contrast, macropinosomes and some phagosomes form with little or no guidance from
      receptors. The common organizing structure is a cup-shaped invagination of the
      plasma membrane that becomes the phagosome or macropinosome. Recent studies,
      focusing on the physical properties of forming cups, indicate that a feedback
      mechanism regulates the signal transduction of phagocytosis and macropinocytosis.

PMID- 18612324
TI  - The use of common mitochondrial variants to detect and characterise population
      structure in the Australian population: implications for genome-wide association
      studies.
AB  - There is an increasing recognition of the potential role of variants in
      mitochondrial DNA and nuclear-encoded mitochondrial proteins in modifying disease
      risk. This has led to a rise in the number of mitochondrial association studies
      being undertaken. The unique inheritance pattern of mitochondria makes
      mitochondrial DNA variation susceptible to having geographical structure. Such a
      structure may have a dramatic impact on mitochondrial association studies,
      particularly in heterogeneous populations. By combining self-reported ancestry
      data and mitochondrial genotype data for a sample of 3839 individuals from 1037
      Australian families, population substructure is tested by looking for evidence of
      differences in mitochondrial haplogroup and single nucleotide polymorphism (SNP)
      frequencies between different ancestral groups in Australia. In addition, the
      substructure within ancestral groups is tested by comparing the similarity of
      mates to randomly drawn pairs of individuals from the same ancestral group. It is
      shown that there are significant differences in the frequency of variants both
      between European and non-European groups, and within Europe. This agrees with
      previous studies of European mitochondrial variation. No evidence was found for
      structure within ancestral groups. These results have implications for future
      association studies in the Australian population, and other populations of
      heterogeneous ancestry.

PMID- 18612325
TI  - A participant-based approach to indoor/outdoor air monitoring in community health
      studies.
AB  - Community health studies of traffic-related air pollution have been hampered by
      the cost and participant burden associated with collecting household-level
      exposure data. The current study utilized a participant-based approach to collect
      indoor and outdoor air monitoring data from 92 asthmatic and nonasthmatic
      children (9-13 years old) enrolled in two concurrent health studies in Detroit,
      Michigan (Mechanistic Indicators of Childhood Asthma and Detroit Children's
      Health Study) conducted by the US Environmental Protection Agency (EPA). Passive
      samplers were shipped to participating households and deployed by parents of
      study participants to collect indoor and outdoor measurements of nitrogen dioxide
      (NO(2)), volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons
      (PAHs) including naphthalene. Half of the households deployed VOC and NO(2)
      samplers for 7 days; the other half deployed PAH and NO(2) samplers for 2 days
      and additional PAH samplers for 1 day. Approximately 88% of the households that
      received air sampling kits completed the air monitoring. Compliance was
      significantly higher among participants asked to deploy all samplers for 7 days
      (85%) compared with participants asked to deploy some samplers for 2 days and
      others for 1 day (56%). The 7-day homes were also more likely to provide usable
      data (96%) compared with the 1- and 2-day homes (73%). Compliance and providing
      usable data did not vary between parents of asthmatic versus nonasthmatic study
      participants and were not reduced among households deploying duplicate samplers.
      These results suggest that participant-based sampling may be a feasible and cost
      effective alternative to traditional exposure assessment approaches that can be
      applied in future epidemiological and community-based health studies.

PMID- 18612326
TI  - Chronic migraine: (when) should we measure CSF pressure?

PMID- 18612327
TI  - Low-molecular-weight heparins should be used with caution in patients with
      chronic kidney disease.

PMID- 18612328
TI  - Should arteriovenous fistulas and synthetic grafts undergo surveillance with pre
      emptive correction of stenosis?
AB  - This Practice Point commentary discusses Tonelli et al.'s systematic review and
      meta-analysis of randomized controlled trials that evaluated surveillance of
      hemodialysis accesses. Tonelli et al. identified studies that used access blood
      flow measurements or duplex ultrasound, and found only four publications of
      native fistulas and seven of synthetic grafts that met their criteria. Study
      quality was not high and statistical power was generally low. Tonelli et al.
      found that fistula surveillance reduced the risk of thrombosis without prolonging
      fistula life, and that graft surveillance showed no benefit. This commentary
      discusses why this small meta-analysis might have been biased towards not finding
      a benefit for stenosis surveillance of grafts by duplex ultrasound. Larger
      multicenter randomized trials are needed to establish the role of surveillance.
      Tonelli et al.'s study will encourage reconsideration of the current
      recommendation in clinical practice guidelines that grafts should undergo routine
      flow surveillance.

PMID- 18612329
TI  - Treating difficult or disruptive dialysis patients: practical strategies based on
      ethical principles.
AB  - For more than a decade, dialysis units have had to contend with an increasing
      number of difficult or disruptive dialysis patients. These individuals present a
      spectrum of behaviors, ranging from those that harm only themselves to those that
      physically endanger dialysis staff. Such behaviors can interfere with the ability
      of the dialysis staff to care for the patient in question and for other patients;
      in addition, threats or actual physical abuse jeopardize the health and safety of
      both patients and staff. In this Review, we discuss how the application of
      ethical principles can assist dialysis staff to balance their ethical obligations
      to disruptive and difficult patients with those to other patients and staff, and
      to establish policies and strategies for the treatment of these challenging
      patients. This approach also allows health-care professionals to identify the
      limited situations in which involuntary patient discharge from a dialysis unit is
      ethically justified.

PMID- 18612331
TI  - Carbocyclic Sinefungin.
AB  - (3aS,4S,6R,6aR)-Tetrahydro-2,2-dimethyl-6-vinyl-3aH-cyclopenta[d][1,3]-dioxol-4
      ol, itself available from ribose, provided a convenient entry point for an 18
      step preparation of carbocyclic sinefungin. This procedure is adaptable to a
      number of carbocyclic sinefungin analogs with diversity of heterocyclic base and
      in the amino acid bearing side chain.

PMID- 18612330
TI  - A new account of the neurocognitive foundations of impairments in space, time and
      number processing in children with chromosome 22q11.2 deletion syndrome.
AB  - In this article, I present an updated account that attempts to explain, in
      cognitive processing and neural terms, the nonverbal intellectual impairments
      experienced by most children with deletions of chromosome 22q11.2. Specifically,
      I propose that this genetic syndrome leads to early developmental changes in the
      structure and function of clearly delineated neural circuits for basic
      spatiotemporal cognition. This dysfunction then cascades into impairments in
      basic magnitude and then numerical processes, because of the central role that
      representations of space and time play in their construction. I propose that this
      takes the form of "spatiotemporal hypergranularity"; the increase in grain size
      and thus reduced resolution of mental representations of spatial and temporal
      information. The result is that spatiotemporal processes develop atypically and
      thereby produce the characteristic impairments in nonverbal cognitive domains
      that are a hallmark feature of chromosome 22q11.2 deletion syndrome. If this
      hypothesis driven account is supported by future research, the results will
      create a neurocognitive explanation of spatiotemporal and numerical impairments
      in the syndrome that is specific enough to be directly translated into the
      development of targeted therapeutic interventions.

PMID- 18612332
TI  - Reaction of an Introverted Carboxylic Acid with Carbodiimide.
AB  - The reaction of carboxylic acids with carbodiimides is reviewed, and an
      "introverted" carboxylic acid is proposed as a means of trapping reactive
      intermediates along the reaction pathway. The introverted acid is a cavitand with
      the carboxylic function directed toward the floor of the cavity. Its reaction
      with diisopropyl carboodiimide gives a covalent adduct that is either the elusive
      O-acylisourea or the commonly encountered N-acylurea.

PMID- 18612357
TI  - Gall-bladder agenesis and associated anomalies.
AB  - Congenital absence of the gall-bladder is a rare condition. It is sometimes
      associated with other congenital defects. We report here two cases of gall
      bladder agenesis discovered at laparoscopy. Both had a history of skeletal and
      cardiovascular anomalies. The investigation of patients with absent gall-bladder
      can be very difficult. Ultrasound scanning is usually inconclusive and further
      noninvasive tests should be performed to establish the diagnosis and prevent an
      unnecessary operation. The presence of other congenital defects should alert the
      clinician to the possibility of gall-bladder agenesis.

PMID- 18612358
TI  - Plasma cholesterol ester fatty acids: a new biochemical abnormality in
      obstructive jaundice.
AB  - Changes in fatty acid patterns may explain many of the observed abnormalities
      found in obstructive jaundice. This study looked at fatty acids in plasma
      cholesterol esters, in a group of patients with obstructive jaundice and a
      matched group of controls. Significant abnormalities were demonstrated, most
      importantly a fall in essential fatty acids, in the jaundiced group. Overall the
      saturation of this fraction, as assessed by double bond index, rose. The
      essential fatty acids are important as factors in membrane function and as
      precursors of eicosanoids. The abnormalities found in this study provide further
      evidence of the significance of EFA in patients with obstructive jaundice.

PMID- 18612369
TI  - Of rodents and humans: a light microscopic and ultrastructural study on
      cardiomyocytes in pulmonary veins.
AB  - Cardiomyocytes in pulmonary veins (PVs) have been reported in rodents and humans.
      In humans they were related to atrial arrhythmias, including atrial fibrillation
      (AF). To investigate histological similarities and differences in PV
      cardiomyocyte localization and distribution, we performed comparative light and
      electron microscopic studies on humans, rats and mice, and generated a transgenic
      mouse strain. Results on mice (C57BL/6 and BALBc) and rats (Wistar) revealed that
      cardiomyocytes regularly extend from the hilus along venous vessels into the lung
      tissue surrounding individual intrapulmonary veins of varying diameters (70-250
      microm). The cardiomyocytes showed the ultrastructure of a normal working
      myocardium with intact intercalated discs and tightly packed contractile
      filaments. In both lung and hilus cardiomyocytes were localized either close to
      the basal lamina of the endothelium or separated from it by smooth muscle cells
      and/or collagen fibres. In humans (autopsies, n=20) extrapericardiac
      cardiomyocytes were only found in 23 out of 78 veins and showed an incomplete
      sleeve at the lung hilus. In addition, cardiomyocytes occurred significantly more
      often in right than in left veins, however, never in intrapulmonary veins. We
      discuss the hypothesis that the variance in distribution of PV cardiomyocytes in
      humans and rodents might reflect the difference in pathogenesis and development
      of AF.

PMID- 18612370
TI  - Ethical perspectives on RNA interference therapeutics.
AB  - RNA interference is a mechanism for controlling normal gene expression which has
      recently begun to be employed as a potential therapeutic agent for a wide range
      of disorders, including cancer, infectious diseases and metabolic disorders.
      Clinical trials with RNA interference have begun. However, challenges such as off
      target effects, toxicity and safe delivery methods have to be overcome before RNA
      interference can be considered as a conventional drug. So, if RNA interference is
      to be used therapeutically, we should perform a risk-benefit analysis. It is
      ethically relevant to perform a risk-benefit analysis since ethical obligations
      about not inflicting harm and promoting good are generally accepted. But the
      ethical issues in RNA interference therapeutics not only include a risk-benefit
      analysis, but also considerations about respecting the autonomy of the patient
      and considerations about justice with regard to the inclusion criteria for
      participation in clinical trials and health care allocation. RNA interference is
      considered a new and promising therapeutic approach, but the ethical issues of
      this method have not been greatly discussed, so this article analyses these
      issues using the bioethical theory of principles of the American bioethicists,
      Tom L. Beauchamp and James F. Childress.

PMID- 18612373
TI  - A Study of Methadone Maintenance For Male Prisoners: 3-Month Postrelease
      Outcomes.
AB  - This study examined benefits of methadone maintenance among prerelease prison
      inmates. Incarcerated males with preincarceration heroin dependence (n = 197)
      were randomly assigned to (a) group educational counseling (counseling only); (b)
      counseling, with opportunity to begin methadone maintenance on release
      (counseling + transfer); or (c) counseling and methadone maintenance in prison,
      with opportunity to continue methadone maintenance on release (counseling +
      methadone). At 90-day follow-up, counseling + methadone participants were
      significantly more likely than counseling-only and counseling + transfer
      participants to attend drug treatment (p = .0001) and less likely to be
      reincarcerated (p = .019). Counseling + methadone and counseling + transfer
      participants were significantly less likely (all ps < .05) to report heroin use,
      cocaine use, and criminal involvement than counseling-only participants. Follow
      up is needed to determine whether these findings hold over a longer period.

PMID- 18612371
TI  - STAT3 activation in pressure-overloaded feline myocardium: role for integrins and
      the tyrosine kinase BMX.
AB  - Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical
      for cardiac hypertrophy. Signal transducer and activator of transcription-3
      (STAT3) activation is an important cardioprotective factor associated with
      cardiac hypertrophy. Although STAT3 activation has been reported via signaling
      through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the
      importance of other nonreceptor tyrosine kinases (NTKs) has not been explored.
      Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of
      hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3
      becomes phosphorylated and redistributed to detergent-insoluble fractions with no
      accompanying JAK2 activation. PO also caused increased levels of phosphorylated
      STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other
      NTKs, we used our established in vitro cell culture model of hypertrophy where
      adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I
      collagen and stimulated with an integrin binding peptide containing an Arg-Gly
      Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion
      complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in
      vitro caused both STAT3 redistribution and activation that were accompanied by
      the activation and redistribution of c-Src and the TEC family kinase, BMX, but
      not JAK2. However, infection with dominant negative c-Src adenovirus was unable
      to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo
      in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent
      insoluble fraction with their complex formation and phosphorylation. Therefore,
      these studies indicate a novel mechanism of BMX-mediated STAT3 activation within
      a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth
      and survival.

PMID- 18612374
TI  - Prevalence and Patterns of Prescription Drug Misuse among Young Ketamine
      Injectors.
AB  - In recent years, epidemiological monitoring data has indicated sharp increases in
      prescription drug misuse. Despite these increases, little is known about the
      context or patterns associated with prescription drug misuse, particularly among
      youth or young injection drug users (IDUs). A three-city study of 213 young IDUs
      found prescription drug misuse to be pervasive, specifically the use of opioids
      and benzodiazepines. Particular practices not commonly associated with
      prescription drugs were reported, such as sniffing, smoking, and injection.
      Associated health risks included initiation into injection drug use, polydrug
      use, drug overdose, and drug dependency. A greater awareness of the potential
      health risks associated with prescription drug misuse should be incorporated into
      services that target IDUs, including street outreach, syringe exchanges, and drug
      treatment.

PMID- 18612375
TI  - A statnet Tutorial.
AB  - The statnet suite of R packages contains a wide range of functionality for the
      statistical analysis of social networks, including the implementation of
      exponential-family random graph (ERG) models. In this paper we illustrate some of
      the functionality of statnet through a tutorial analysis of a friendship network
      of 1,461 adolescents.

PMID- 18612377
TI  - Functional analysis of spontaneous cell movement under different physiological
      conditions.
AB  - Cells can show not only spontaneous movement but also tactic responses to
      environmental signals. Since the former can be regarded as the basis to realize
      the latter, playing essential roles in various cellular functions, it is
      important to investigate spontaneous movement quantitatively at different
      physiological conditions in relation to a cell's physiological functions. For
      that purpose, we observed a series of spontaneous movements by Dictyostelium
      cells at different developmental periods by using a single cell tracking system.
      Using statistical analysis of these traced data, we found that cells showed
      complex dynamics with anomalous diffusion and that their velocity distribution
      had power-law tails in all conditions. Furthermore, as development proceeded,
      average velocity and persistency of the movement increased and as too did the
      exponential behavior in the velocity distribution. Based on these results, we
      succeeded in applying a generalized Langevin model to the experimental data. With
      this model, we discuss the relation of spontaneous cell movement to cellular
      physiological function and its relevance to behavioral strategies for cell
      survival.

PMID- 18612378
TI  - Systematic evaluation of candidate blood markers for detecting ovarian cancer.
AB  - BACKGROUND: Epithelial ovarian cancer is a significant cause of mortality both in
      the United States and worldwide, due largely to the high proportion of cases that
      present at a late stage, when survival is extremely poor. Early detection of
      epithelial ovarian cancer, and of the serous subtype in particular, is a
      promising strategy for saving lives. The low prevalence of ovarian cancer makes
      the development of an adequately sensitive and specific test based on blood
      markers very challenging. We evaluated the performance of a set of candidate
      blood markers and combinations of these markers in detecting serous ovarian
      cancer. METHODS AND FINDINGS: We selected 14 candidate blood markers of serous
      ovarian cancer for which assays were available to measure their levels in serum
      or plasma, based on our analysis of global gene expression data and on literature
      searches. We evaluated the performance of these candidate markers individually
      and in combination by measuring them in overlapping sets of serum (or plasma)
      samples from women with clinically detectable ovarian cancer and women without
      ovarian cancer. Based on sensitivity at high specificity, we determined that 4 of
      the 14 candidate markers--MUC16, WFDC2, MSLN and MMP7--warrant further evaluation
      in precious serum specimens collected months to years prior to clinical diagnosis
      to assess their utility in early detection. We also reported differences in the
      performance of these candidate blood markers across histological types of
      epithelial ovarian cancer. CONCLUSIONS: By systematically analyzing the
      performance of candidate blood markers of ovarian cancer in distinguishing women
      with clinically apparent ovarian cancer from women without ovarian cancer, we
      identified a set of serum markers with adequate performance to warrant testing
      for their ability to identify ovarian cancer months to years prior to clinical
      diagnosis. We argued for the importance of sensitivity at high specificity and of
      magnitude of difference in marker levels between cases and controls as
      performance metrics and demonstrated the importance of stratifying analyses by
      histological type of ovarian cancer. Also, we discussed the limitations of
      studies (like this one) that use samples obtained from symptomatic women to
      assess potential utility in detection of disease months to years prior to
      clinical detection.

PMID- 18612376
TI  - Diverse roles of androgen receptor (AR) domains in AR-mediated signaling.
AB  - Androgens control male sexual development and maintenance of the adult male
      phenotype. They have very divergent effects on their target organs like the
      reproductive organs, muscle, bone, brain and skin. This is explained in part by
      the fact that different cell types respond differently to androgen stimulus, even
      when all these responses are mediated by the same intracellular androgen
      receptor. To understand these tissue- and cell-specific readouts of androgens, we
      have to learn the many different steps in the transcription activation mechanisms
      of the androgen receptor (NR3C4). Like all nuclear receptors, the steroid
      receptors have a central DNA-binding domain connected to a ligand-binding domain
      by a hinge region. In addition, all steroid receptors have a relatively large
      amino-terminal domain. Despite the overall structural homology with other nuclear
      receptors, the androgen receptor has several specific characteristics which will
      be discussed here. This receptor can bind two types of androgen response elements
      (AREs): one type being similar to the classical GRE/PRE-type elements, the other
      type being the more divergent and more selective AREs. The hormone-binding domain
      has low intrinsic transactivation properties, a feature that correlates with the
      low affinity of this domain for the canonical LxxLL-bearing coactivators. For the
      androgen receptor, transcriptional activation involves the alternative
      recruitment of coactivators to different regions in the amino-terminal domain, as
      well as the hinge region. Finally, a very strong ligand-induced interaction
      between the amino-terminal domain and the ligand-binding domain of the androgen
      receptor seems to be involved in many aspects of its function as a transcription
      factor. This review describes the current knowledge on the structure-function
      relationships within the domains of the androgen receptor and tries to integrate
      the involvement of different domains, subdomains and motifs in the functioning of
      this receptor as a transcription factor with tissue- and cell-specific readouts.

PMID- 18612379
TI  - Lifespan mental activity predicts diminished rate of hippocampal atrophy.
AB  - OBJECTIVE: Epidemiological studies suggest that complex mental activity may
      reduce the risk for dementia, however an underlying mechanism remains unclear.
      Our objective was to determine whether individual differences in lifespan complex
      mental activity are linked to altered rates of hippocampal atrophy independent of
      global measures of neurodegeneration. METHODS: Thirty seven healthy older
      individuals had their complex mental activity levels estimated using the Lifetime
      of Experiences Questionnaire (LEQ) and completed serial MRI investigations at
      baseline and three years follow-up. Hippocampal volume and semi-automatic
      quantitation of whole brain volume (WBV) and white matter hyperintensities (WMHs)
      were compared at both time points. RESULTS: Higher LEQ scores were correlated
      with hippocampal volume independent of covariates at the three year follow-up
      stage (r = 0.43, p = 0.012). Moreover, those with higher LEQ scores experienced
      less hippocampal atrophy over the follow-up period (r = 0.41, p = 0.02). High LEQ
      individuals had less than half the hippocampal volume decline of low LEQ
      individuals in a multivariate analysis (F = 4.47, p = 0.042). No parallel changes
      were found in measures of WBV and WMHs. CONCLUSIONS: High level of complex mental
      activity across the lifespan was correlated with a reduced rate of hippocampal
      atrophy. This finding could not be explained by general differences in
      intracranial volume, larger hippocampi at baseline, presence of hypertensive
      disease, gender or low mood. Our results suggest that neuroprotection in medial
      temporal lobe may be one mechanism underlying the link between mental activity
      and lower rates of dementia observed in population-based studies. Additional
      studies are required to further explore this novel finding.

PMID- 18612380
TI  - fMRI evidence for a dual process account of the speed-accuracy tradeoff in
      decision-making.
AB  - BACKGROUND: The speed and accuracy of decision-making have a well-known trading
      relationship: hasty decisions are more prone to errors while careful, accurate
      judgments take more time. Despite the pervasiveness of this speed-accuracy trade
      off (SAT) in decision-making, its neural basis is still unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging
      (fMRI) we show that emphasizing the speed of a perceptual decision at the expense
      of its accuracy lowers the amount of evidence-related activity in lateral
      prefrontal cortex. Moreover, this speed-accuracy difference in lateral prefrontal
      cortex activity correlates with the speed-accuracy difference in the decision
      criterion metric of signal detection theory. We also show that the same
      instructions increase baseline activity in a dorso-medial cortical area involved
      in the internal generation of actions. CONCLUSIONS/SIGNIFICANCE: These findings
      suggest that the SAT is neurally implemented by modulating not only the amount of
      externally-derived sensory evidence used to make a decision, but also the
      internal urge to make a response. We propose that these processes combine to
      control the temporal dynamics of the speed-accuracy trade-off in decision-making.

PMID- 18612382
TI  - Modified whole-mount in situ hybridization protocol for the detection of
      transgene expression in electroporated chick embryos.
AB  - BACKGROUND: In vivo electroporation has been extensively used as an effective
      means of DNA transfer for analyzing gene function as well as gene regulation in
      developmental systems. In any of these two types of studies, the correct spatial
      and temporal expression of the electroporated transgene can only be accurately
      assessed by in situ hybridization. METHODOLOGY/PRINCIPAL FINDINGS: While
      analyzing transgene expression in electroporated chicken embryos, we verified
      that transgene riboprobes cross-hybridized with the exogenous plasmid DNA when
      embryos were processed by conventional whole-mount in situ hybridization (WISH).
      CONCLUSIONS/SIGNIFICANCE: Here we describe a modification to the WISH protocol
      that is essential to prevent DNA cross-hybridization and to specifically detect
      transgene mRNA transcripts in electroporated embryos. Our optimized WISH
      procedure can be applied not only to electroporated chick embryos but also to
      other embryos or adult tissues that have been transfected with large amounts of
      reporter- or expression construct DNA.

PMID- 18612381
TI  - Use of evidence-based practices in pregnancy and childbirth: South East Asia
      Optimising Reproductive and Child Health in Developing Countries project.
AB  - BACKGROUND: The burden of mortality and morbidity related to pregnancy and
      childbirth remains concentrated in developing countries. SEA-ORCHID (South East
      Asia Optimising Reproductive and Child Health In Developing countries) is
      evaluating whether a multifaceted intervention to strengthen capacity for
      research synthesis, evidence-based care and knowledge implementation improves
      adoption of best clinical practice recommendations leading to better health for
      mothers and babies. In this study we assessed current practices in perinatal
      health care in four South East Asian countries and determined whether they were
      aligned with best practice recommendations. METHODOLOGY/PRINCIPAL FINDINGS: We
      completed an audit of 9550 medical records of women and their 9665 infants at
      nine hospitals; two in each of Indonesia, Malaysia and The Philippines, and three
      in Thailand between January-December 2005. We compared actual clinical practices
      with best practice recommendations selected from the Cochrane Library and the
      World Health Organization Reproductive Health Library. Evidence-based components
      of the active management of the third stage of labour and appropriately treating
      eclampsia with magnesium sulphate were universally practiced in all hospitals.
      Appropriate antibiotic prophylaxis for caesarean section, a beneficial form of
      care, was practiced in less than 5% of cases in most hospitals. Use of the
      unnecessary practices of enema in labour ranged from 1% to 61% and rates of
      episiotomy for vaginal birth ranged from 31% to 95%. Other appropriate practices
      were commonly performed to varying degrees between countries and also between
      hospitals within the same country. CONCLUSIONS/SIGNIFICANCE: Whilst some
      perinatal health care practices audited were consistent with best available
      evidence, several were not. We conclude that recording of clinical practices
      should be an essential step to improve quality of care. Based on these findings,
      the SEA-ORCHID project team has been developing and implementing interventions
      aimed at increasing compliance with evidence-based clinical practice
      recommendations to improve perinatal practice in South East Asia.

PMID- 18612383
TI  - The C/H3 domain of p300 is required to protect VRK1 and VRK2 from their
      downregulation induced by p53.
AB  - BACKGROUND: The vaccinia-related kinase 1 (VRK1) protein, an activator of p53,
      can be proteolytically downregulated by an indirect mechanism, which requires p53
      dependent transcription. PRINCIPAL FINDINGS: In this work we have biochemically
      characterized the contribution of several p53 transcriptional cofactors with
      acetyl transferase activity to the induction of VRK1 downregulation that was used
      as a functional assay. Downregulation of VRK1 induced by p53 is prevented in a
      dose dependent manner by either p300 or CBP, but not by PCAF, used as
      transcriptional co-activators, suggesting that p53 has a different specificity
      depending on the relative level of these transcriptional cofactors. This
      inhibition does not require p53 acetylation, since a p53 acetylation mutant also
      induces VRK1 downregulation. PCAF can not revert the VRK1 protection effect of
      p300, indicating that these two proteins do not compete for a common factor
      needed to induce VRK1 downregulation. The protective effect is also induced by
      the C/H3 domain of p300, a region implicated in binding to several transcription
      factors and SV40 large T antigen; but the protective effect is lost when a mutant
      C/H3Del33 is used. The protective effect is a consequence of direct binding of
      the C/H3 domain to the transactivation domain of p53. A similar downregulatory
      effect can also be detected with VRK2 protein. CONCLUSIONS/SIGNIFICANCE: Specific
      p53-dependent effects are determined by the availability and ratios of its
      transcriptional cofactors. Specifically, the downregulation of VRK1/VRK2 protein
      levels, as a consequence of p53 accumulation, is thus dependent on the levels of
      the p300/CBP protein available for transcriptional complexes, since in this
      context this cofactor functions as a repressor of the effect. These observations
      point to the relevance of knowing the cofactor levels in order to determine one
      effect or another.

PMID- 18612384
TI  - Tankyrase 1 and tankyrase 2 are essential but redundant for mouse embryonic
      development.
AB  - Tankyrases are proteins with poly(ADP-ribose) polymerase activity. Human
      tankyrases post-translationally modify multiple proteins involved in processes
      including maintenance of telomere length, sister telomere association, and
      trafficking of glut4-containing vesicles. To date, however, little is known about
      in vivo functions for tankyrases. We recently reported that body size was
      significantly reduced in mice deficient for tankyrase 2, but that these mice
      otherwise appeared developmentally normal. In the present study, we report
      generation of tankyrase 1-deficient and tankyrase 1 and 2 double-deficient mice,
      and use of these mutant strains to systematically assess candidate functions of
      tankyrase 1 and tankyrase 2 in vivo. No defects were observed in development,
      telomere length maintenance, or cell cycle regulation in tankyrase 1 or tankyrase
      2 knockout mice. In contrast to viability and normal development of mice singly
      deficient in either tankyrase, deficiency in both tankyrase 1 and tankyrase 2
      results in embryonic lethality by day 10, indicating that there is substantial
      redundancy between tankyrase 1 and tankyrase 2, but that tankyrase function is
      essential for embryonic development.

PMID- 18612385
TI  - Finite size effects in simulations of protein aggregation.
AB  - It is becoming increasingly clear that the soluble protofibrillar species that
      proceed amyloid fibril formation are associated with a range of neurodegenerative
      disorders such as Alzheimer's and Parkinson diseases. Computer simulations of the
      processes that lead to the formation of these oligomeric species are starting to
      make significant contributions to our understanding of the determinants of
      protein aggregation. We simulate different systems at constant concentration but
      with a different number of peptides and we study the how the finite number of
      proteins affects the underlying free energy of the system and therefore the
      relative stability of the species involved in the process. If not taken into
      account, this finite size effect can undermine the validity of theoretical
      predictions regarding the relative stability of the species involved and the
      rates of conversion from one to the other. We discuss the reasons that give rise
      to this finite size effect form both a probabilistic and energy fluctuations
      point of view and also how this problem can be dealt by a finite size scaling
      analysis.

PMID- 18612386
TI  - The role of cardiac troponin T quantity and function in cardiac development and
      dilated cardiomyopathy.
AB  - BACKGROUND: Hypertrophic (HCM) and dilated (DCM) cardiomyopathies result from
      sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We
      determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT
      function or quantity; whether the severity of DCM is related to the ratio of
      mutant to wildtype cTnT; whether Ca(2+) desensitization occurs in DCM; and
      whether absence of cTnT impairs early embryonic cardiogenesis. METHODS AND
      FINDINGS: We ablated Tnnt2 to produce heterozygous Tnnt2(+/-) mice, and
      crossbreeding produced homozygous null Tnnt2(-/-) embryos. We also generated
      transgenic mice overexpressing wildtype (TG(WT)) or DCM mutant (TG(K210Delta))
      Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying
      wildtype (Tnnt2(+/-)/TG(WT)) or mutant (Tnnt2(+/-)/TG(K210Delta)) transgenes.
      Tnnt2(+/-) mice relative to wildtype had significantly reduced transcript (0.82+/
      0.06[SD] vs. 1.00+/-0.12 arbitrary units; p = 0.025), but not protein (1.01+/
      0.20 vs. 1.00+/-0.13 arbitrary units; p = 0.44). Tnnt2(+/-) mice had normal
      hearts (histology, mass, left ventricular end diastolic diameter [LVEDD],
      fractional shortening [FS]). Moreover, whereas Tnnt2(+/-)/TG(K210Delta) mice had
      severe DCM, TG(K210Delta) mice had only mild DCM (FS 18+/-4 vs. 29+/-7%; p<0.01).
      The difference in severity of DCM may be attributable to a greater ratio of
      mutant to wildtype Tnnt2 transcript in Tnnt2(+/-)/TG(K210Delta) relative to
      TG(K210Delta) mice (2.42+/-0.08, p = 0.03). Tnnt2(+/-)/TG(K210Delta) muscle
      showed Ca(2+) desensitization (pCa(50) = 5.34+/-0.08 vs. 5.58+/-0.03 at sarcomere
      length 1.9 microm, p<0.01), but no difference in maximum force generation. Day
      9.5 Tnnt2(-/-) embryos had normally looped hearts, but thin ventricular walls,
      large pericardial effusions, noncontractile hearts, and severely disorganized
      sarcomeres. CONCLUSIONS: Absence of one Tnnt2 allele leads to a mild deficit in
      transcript but not protein, leading to a normal cardiac phenotype. DCM results
      from abnormal function of a mutant protein, which is associated with myocyte
      Ca(2+) desensitization. The severity of DCM depends on the ratio of mutant to
      wildtype Tnnt2 transcript. cTnT is essential for sarcomere formation, but normal
      embryonic heart looping occurs without contractile activity.

PMID- 18612389
TI  - About hearsay - or reappraisal of the role of the anamnesis as an instrument of
      meaningful communication.
AB  - As a result of the ICT revolution and enhancement of diagnostic possibilities,
      the anamnesis, as an instrument of meaningful communication in disease and a
      cornerstone of medical practice throughout the ages, has lost in importance.
      Nowadays, we are on the brink of a more patient-tailored and individualised
      therapy, so there is a growing need for an open dialogue in the doctor-patient
      relationship, a situation very similar to the beginning of the
      professionalisation of assistance in disease in ancient medicine. Reappraisal of
      the anamnesis and awareness of the patient-doctor relationship are therefore
      warranted and for that reason its roots and evolution are discussed from a
      historic perspective. (Neth Heart J 2007;15:359-62.).

PMID- 18612387
TI  - The actinome of Dictyostelium discoideum in comparison to actins and actin
      related proteins from other organisms.
AB  - Actin belongs to the most abundant proteins in eukaryotic cells which harbor
      usually many conventional actin isoforms as well as actin-related proteins
      (Arps). To get an overview over the sometimes confusing multitude of actins and
      Arps, we analyzed the Dictyostelium discoideum actinome in detail and compared it
      with the genomes from other model organisms. The D. discoideum actinome comprises
      41 actins and actin-related proteins. The genome contains 17 actin genes which
      most likely arose from consecutive gene duplications, are all active, in some
      cases developmentally regulated and coding for identical proteins (Act8-group).
      According to published data, the actin fraction in a D. discoideum cell consists
      of more than 95% of these Act8-type proteins. The other 16 actin isoforms contain
      a conventional actin motif profile as well but differ in their protein sequences.
      Seven actin genes are potential pseudogenes. A homology search of the human
      genome using the most typical D. discoideum actin (Act8) as query sequence finds
      the major actin isoforms such as cytoplasmic beta-actin as best hit. This
      suggests that the Act8-group represents a nearly perfect actin throughout
      evolution. Interestingly, limited data from D. fasciculatum, a more ancient
      member among the social amoebae, show different relationships between
      conventional actins. The Act8-type isoform is most conserved throughout
      evolution. Modeling of the putative structures suggests that the majority of the
      actin-related proteins is functionally unrelated to canonical actin. The data
      suggest that the other actin variants are not necessary for the cytoskeleton
      itself but rather regulators of its dynamical features or subunits in larger
      protein complexes.

PMID- 18612388
TI  - Birds reveal their personality when singing.
AB  - BACKGROUND: Individual differences in social behaviour may have consequences for
      mate choice and sexual signalling, because partners should develop preferences
      for personalities that maximize reproductive output. Here we propose that
      behavioural traits involved in sexual advertisement may serve as good indicators
      of personality, which is fundamental for sexual selection to operate on
      temperament. Bird song has a prominent and well-established role in sexual
      selection, and it displays considerable variation among individuals with a
      potentially strong personality component. Therefore, we predicted that features
      of song would correlate with estimates of personality. METHODOLOGY/PRINCIPAL
      FINDINGS: In a field study of free-living male collared flycatchers, Ficedula
      albicollis, we characterised personality based on the exploration of an altered
      breeding environment, and based on the risk taken when a potential predator was
      approaching during a simulated territorial interaction. We found that explorative
      and risk-taker individuals consistently sang at lower song posts than shy
      individuals in the presence of a human observer. Moreover, males from lower posts
      established pair-bonds relatively faster than males from higher posts.
      CONCLUSIONS/SIGNIFICANCE: Our results may demonstrate that risk taking during
      singing correlates with risk taking during aggression and with exploration, thus
      personality may be manifested in different contexts involving sexual
      advertisement. These findings are in accordance with the hypothesis that the
      male's balance between investment in reproduction and risk taking is reflected in
      sexual displays, and it may be important information for choosy females that seek
      partners with personality traits enhancing breeding success.

PMID- 18612390
TI  - Coronary stent healing, endothelialisation and the role of co-medication.

PMID- 18612391
TI  - Epigenetic histone acetylation modifiers in vascular remodelling - new targets
      for therapy in cardiovascular disease.

PMID- 18612392
TI  - Identification of a common gene expression response in different lung
      inflammatory diseases in rodents and macaques.
AB  - To identify gene expression responses common to multiple pulmonary diseases we
      collected microarray data for acute lung inflammation models from 12 studies and
      used these in a meta-analysis. The data used include exposures to air pollutants;
      bacterial, viral, and parasitic infections; and allergic asthma models.
      Hierarchical clustering revealed a cluster of 383 up-regulated genes with a
      common response. This cluster contained five subsets, each characterized by more
      specific functions such as inflammatory response, interferon-induced genes,
      immune signaling, or cell proliferation. Of these subsets, the inflammatory
      response was common to all models, interferon-induced responses were more
      pronounced in bacterial and viral models, and a cell division response was more
      prominent in parasitic and allergic models. A common cluster containing 157
      moderately down-regulated genes was associated with the effects of tissue damage.
      Responses to influenza in macaques were weaker than in mice, reflecting
      differences in the degree of lung inflammation and/or virus replication. The
      existence of a common cluster shows that in vivo lung inflammation in response to
      various pathogens or exposures proceeds through shared molecular mechanisms.

PMID- 18612393
TI  - A molecular study of microbe transfer between distant environments.
AB  - BACKGROUND: Environments and their organic content are generally not static and
      isolated, but in a constant state of exchange and interaction with each other.
      Through physical or biological processes, organisms, especially microbes, may be
      transferred between environments whose characteristics may be quite different.
      The transferred microbes may not survive in their new environment, but their DNA
      will be deposited. In this study, we compare two environmental sequencing
      projects to find molecular evidence of transfer of microbes over vast
      geographical distances. METHODOLOGY: By studying synonymous nucleotide
      composition, oligomer frequency and orthology between predicted genes in
      metagenomics data from two environments, terrestrial and aquatic, and by
      correlating with phylogenetic mappings, we find that both environments are likely
      to contain trace amounts of microbes which have been far removed from their
      original habitat. We also suggest a bias in direction from soil to sea, which is
      consistent with the cycles of planetary wind and water. CONCLUSIONS: Our findings
      support the Baas-Becking hypothesis formulated in 1934, which states that due to
      dispersion and population sizes, microbes are likely to be found in widely
      disparate environments. Furthermore, the availability of genetic material from
      distant environments is a possible font of novel gene functions for lateral gene
      transfer.

PMID- 18612394
TI  - Both functional LTbeta receptor and TNF receptor 2 are required for the
      development of experimental cerebral malaria.
AB  - BACKGROUND: TNF-related lymphotoxin alpha (LTalpha) is essential for the
      development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral
      malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a
      second arm of LTalpha-signaling essential for ECM development through LTbeta-R,
      receptor of LTalpha1beta2 heterotrimer. METHODOLOGY/PRINCIPAL FINDINGS: LTbetaR
      deficient mice did not develop the neurological signs seen in PbA induced ECM but
      died at three weeks with high parasitaemia and severe anemia like LTalphabeta
      deficient mice. Resistance of LTalphabeta or LTbetaR deficient mice correlated
      with unaltered cerebral microcirculation and absence of ischemia, as documented
      by magnetic resonance imaging and angiography, associated with lack of
      microvascular obstruction, while wild-type mice developed distinct microvascular
      pathology. Recruitment and activation of perforin(+) CD8(+) T cells, and their
      ICAM-1 expression were clearly attenuated in the brain of resistant mice. An
      essential contribution of LIGHT, another LTbetaR ligand, could be excluded, as
      LIGHT deficient mice rapidly succumbed to ECM. CONCLUSIONS/SIGNIFICANCE: LTbetaR
      expressed on radioresistant resident stromal, probably endothelial cells, rather
      than hematopoietic cells, are essential for the development of ECM, as assessed
      by hematopoietic reconstitution experiment. Therefore, the data suggest that both
      functional LTbetaR and TNFR2 signaling are required and non-redundant for the
      development of microvascular pathology resulting in fatal ECM.

PMID- 18612395
TI  - Should laparoscopic surgery be an outpatient procedure?

PMID- 18612396
TI  - Is repeated hepatic resection justified for malignancy?

PMID- 18612397
TI  - Pancreatic drainage into the stomach after pancreatic resection.

PMID- 18612398
TI  - Prediction of severity in acute pancreatitis.

PMID- 18612400
TI  - The Warren shunt: effect of alcoholism on portal perfusion.

PMID- 18612408
TI  - Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).
AB  - Aquaporins (AQPs) have previously been associated with increased expression in
      solid tumors. However, its expression in hematologic malignancies including CML
      has not been described yet. Here, we report the expression of AQP5 in CML cells
      by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n =
      5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated
      AQP5 expression. In addition, AQP5 expression level increased with the emergence
      of imatinib mesylate resistance in paired samples (p = 0.047). We have found that
      the overexpression of AQP5 in K562 cells resulted in increased cell
      proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced
      the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by
      immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is
      increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated
      CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated
      cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from
      bone marrow. In summary, we report for the first time that AQP5 is overexpressed
      in CML cells and plays a role in promoting cell proliferation and inhibiting
      apoptosis. Furthermore, our findings may provide the basis for a novel CML
      therapy targeting AQP5.

PMID- 18612409
TI  - Variants of ST8SIA1 are associated with risk of developing multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system of unknown etiology with both genetic and environmental factors
      playing a role in susceptibility. To date, the HLA DR15/DQ6 haplotype within the
      major histocompatibility complex on chromosome 6p, is the strongest genetic risk
      factor associated with MS susceptibility. Additional alleles of IL7 and IL2 have
      been identified as risk factors for MS with small effect. Here we present two
      independent studies supporting an allelic association of MS with polymorphisms in
      the ST8SIA1 gene, located on chromosome 12p12 and encoding ST8 alpha-N-acetyl
      neuraminide alpha-2,8-sialyltransferase 1. The initial association was made in a
      single three-generation family where a single-nucleotide polymorphism (SNP)
      rs4762896, was segregating together with HLA DR15/DQ6 in MS patients. A study of
      274 family trios (affected child and both unaffected parents) from Australia
      validated the association of ST8SIA1 in individuals with MS, showing transmission
      disequilibrium of the paternal alleles for three additional SNPs, namely
      rs704219, rs2041906, and rs1558793, with p = 0.001, p = 0.01 and p = 0.01
      respectively. These findings implicate ST8SIA1 as a possible novel susceptibility
      gene for MS.

PMID- 18612410
TI  - Local alignment refinement using structural assessment.
AB  - Homology modeling is the most commonly used technique to build a three
      dimensional model for a protein sequence. It heavily relies on the quality of the
      sequence alignment between the protein to model and related proteins with a known
      three dimensional structure. Alignment quality can be assessed according to the
      physico-chemical properties of the three dimensional models it produces. In this
      work, we introduce fifteen predictors designed to evaluate the properties of the
      models obtained for various alignments. They consist of an energy value obtained
      from different force fields (CHARMM, ProsaII or ANOLEA) computed on residue
      selected around misaligned regions. These predictors were evaluated on ten
      challenging test cases. For each target, all possible ungapped alignments are
      generated and their corresponding models are computed and evaluated. The best
      predictor, retrieving the structural alignment for 9 out of 10 test cases, is
      based on the ANOLEA atomistic mean force potential and takes into account
      residues around misaligned secondary structure elements. The performance of the
      other predictors is significantly lower. This work shows that substantial
      improvement in local alignments can be obtained by careful assessment of the
      local structure of the resulting models.

PMID- 18612411
TI  - Prenatal activation of microglia induces delayed impairment of glutamatergic
      synaptic function.
AB  - BACKGROUND: Epidemiological studies have linked maternal infection during
      pregnancy to later development of neuropsychiatric disorders in the offspring. In
      mice, experimental inflammation during embryonic development impairs behavioral
      and cognitive performances in adulthood. Synaptic dysfunctions may be at the
      origin of cognitive impairments, however the link between prenatal inflammation
      and synaptic defects remains to be established. METHODOLOGY/PRINCIPAL FINDINGS:
      In this study, we show that prenatal alteration of microglial function, including
      inflammation, induces delayed synaptic dysfunction in the adult. DAP12 is a
      microglial signaling protein expressed around birth, mutations of which in the
      human induces the Nasu-Hakola disease, characterized by early dementia. We
      presently report that synaptic excitatory currents in mice bearing a loss-of
      function mutation in the DAP12 gene (DAP12(KI) mice) display enhanced relative
      contribution of AMPA. Furthermore, neurons from DAP12(KI) P0 pups cultured
      without microglia develop similar synaptic alterations, suggesting that a
      prenatal dysfunction of microglia may impact synaptic function in the adult. As
      we observed that DAP12(KI) microglia overexpress genes for IL1beta, IL6 and NOS2,
      which are inflammatory proteins, we analyzed the impact of a pharmacologically
      induced prenatal inflammation on synaptic function. Maternal injection of
      lipopolysaccharides induced activation of microglia at birth and alteration of
      glutamatergic synapses in the adult offspring. Finally, neurons cultured from
      neonates born to inflamed mothers and cultured without microglia also displayed
      altered neuronal activity. CONCLUSION/SIGNIFICANCE: Our results demonstrate that
      prenatal inflammation is sufficient to induce synaptic alterations with delay. We
      propose that these alterations triggered by prenatal activation of microglia
      provide a cellular basis for the neuropsychiatric defects induced by prenatal
      inflammation.

PMID- 18612412
TI  - The pleiotropic effects of simvastatin on retinal microvascular endothelium has
      important implications for ischaemic retinopathies.
AB  - BACKGROUND: Current guidelines encourage the use of statins to reduce the risk of
      cardiovascular disease in diabetic patients; however the impact of these drugs on
      diabetic retinopathy is not well defined. Moreover, pleiotropic effects of
      statins on the highly specialised retinal microvascular endothelium remain
      largely unknown. The objective of this study was to investigate the effects of
      clinically relevant concentrations of simvastatin on retinal endothelium in vitro
      and in vivo. METHODS AND FINDINGS: Retinal microvascular endothelial cells
      (RMECs) were treated with 0.01-10 microM simvastatin and a biphasic dose-related
      response was observed. Low concentrations enhanced microvascular repair with 0.1
      microM simvastatin significantly increasing proliferation (p<0.05), and 0.01
      microM simvastatin significantly promoting migration (p<0.05), sprouting
      (p<0.001), and tubulogenesis (p<0.001). High concentration of simvastatin (10
      microM) had the opposite effect, significantly inhibiting proliferation (p<0.01),
      migration (p<0.01), sprouting (p<0.001), and tubulogenesis (p<0.05). Furthermore,
      simvastatin concentrations higher than 1 microM induced cell death. The mouse
      model of oxygen-induced retinopathy was used to investigate the possible effects
      of simvastatin treatment on ischaemic retinopathy. Low dose simvastatin (0.2
      mg/Kg) promoted retinal microvascular repair in response to ischaemia by
      promoting intra-retinal re-vascularisation (p<0.01). By contrast, high dose
      simvastatin(20 mg/Kg) significantly prevented re-vascularisation (p<0.01) and
      concomitantly increased pathological neovascularisation (p<0.01). We also
      demonstrated that the pro-vascular repair mechanism of simvastatin involves VEGF
      stimulation, Akt phosphorylation, and nitric oxide production; and the anti
      vascular repair mechanism is driven by marked intracellular cholesterol depletion
      and related disorganisation of key intracellular structures. CONCLUSIONS: A
      beneficial effect of low-dose simvastatin on ischaemic retinopathy is linked to
      angiogenic repair reducing ischaemia, thereby preventing pathological
      neovascularisation. High-dose simvastatin may be harmful by inhibiting reparative
      processes and inducing premature death of retinal microvascular endothelium which
      increases ischaemia-induced neovascular pathology. Statin dosage should be
      judiciously monitored in patients who are diabetic or are at risk of developing
      other forms of proliferative retinopathy.

PMID- 18612413
TI  - Ubiquitination is required for effective replication of coxsackievirus B3.
AB  - BACKGROUND: Protein ubiquitination and/or degradation by the ubiquitin/proteasome
      system (UPS) have been recognized as critical mechanisms in the regulation of
      numerous essential cellular functions. The importance of the UPS in viral
      pathogenesis has become increasingly apparent. Using murine cardiomyocytes, we
      have previously demonstrated that the UPS plays a key role in the replication of
      coxsackievirus B3 (CVB3), an important human pathogen associated with various
      diseases. To further elucidate the underlying mechanisms, we examined the
      interplay between the UPS and CVB3, focusing on the role of ubiquitination in
      viral lifecycle. METHODOLOGY/PRINCIPAL FINDINGS: As assessed by in situ
      hybridization, Western blot, and plaque assay, we showed that proteasome
      inhibition decreased CVB3 RNA replication, protein synthesis, and viral titers in
      HeLa cells. There were no apparent changes in 20S proteasome activities following
      CVB3 infection. However, we found viral infection led to an accumulation of
      protein-ubiquitin conjugates, accompanied by a decreased protein expression of
      free ubiquitin, implicating an important role of ubiquitination in the UPS
      mediated viral replication. Using small-interfering RNA, we demonstrated that
      gene-silencing of ubiquitin significantly reduced viral titers, possibly through
      downregulation of protein ubiquitination and subsequent alteration of protein
      function and/or degradation. Inhibition of deubiquitinating enzymes apparently
      enhances the inhibitory effects of proteasome inhibitors on CVB3 replication.
      Finally, by immunoprecipitation, we showed that coxsackieviral polymerase 3D was
      post-translationally modified by ubiquitination and such modification might be a
      prerequisite for its function in transcriptional regulation of viral genome.
      CONCLUSION: Coxsackievirus infection promotes protein ubiquitination,
      contributing to effective viral replication, probably through ubiquitin
      modification of viral polymerase.

PMID- 18612414
TI  - Hedonic taste in Drosophila revealed by olfactory receptors expressed in taste
      neurons.
AB  - Taste and olfaction are each tuned to a unique set of chemicals in the outside
      world, and their corresponding sensory spaces are mapped in different areas in
      the brain. This dichotomy matches categories of receptors detecting molecules
      either in the gaseous or in the liquid phase in terrestrial animals. However, in
      Drosophila olfactory and gustatory neurons express receptors which belong to the
      same family of 7-transmembrane domain proteins. Striking overlaps exist in their
      sequence structure and in their expression pattern, suggesting that there might
      be some functional commonalities between them. In this work, we tested the
      assumption that Drosophila olfactory receptor proteins are compatible with taste
      neurons by ectopically expressing an olfactory receptor (OR22a and OR83b) for
      which ligands are known. Using electrophysiological recordings, we show that the
      transformed taste neurons are excited by odor ligands as by their cognate
      tastants. The wiring of these neurons to the brain seems unchanged and no
      additional connections to the antennal lobe were detected. The odor ligands
      detected by the olfactory receptor acquire a new hedonic value, inducing
      appetitive or aversive behaviors depending on the categories of taste neurons in
      which they are expressed i.e. sugar- or bitter-sensing cells expressing either
      Gr5a or Gr66a receptors. Taste neurons expressing ectopic olfactory receptors can
      sense odors at close range either in the aerial phase or by contact, in a
      lipophilic phase. The responses of the transformed taste neurons to the odorant
      are similar to those obtained with tastants. The hedonic value attributed to
      tastants is directly linked to the taste neurons in which their receptors are
      expressed.

PMID- 18612415
TI  - Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma
      membrane luciferase.
AB  - BACKGROUND: There is growing awareness that tumour cells build up a "self
      advantageous" microenvironment that reduces effectiveness of anti-tumour immune
      response. While many different immunosuppressive mechanisms are likely to come
      into play, recent evidence suggests that extracellular adenosine acting at A2A
      receptors may have a major role in down-modulating the immune response as
      cancerous tissues contain elevated levels of adenosine and adenosine break-down
      products. While there is no doubt that all cells possess plasma membrane
      adenosine transporters that mediate adenosine uptake and may also allow its
      release, it is now clear that most of extracellularly-generated adenosine
      originates from the catabolism of extracellular ATP. METHODOLOGY/PRINCIPAL
      FINDINGS: Measurement of extracellular ATP is generally performed in cell
      supernatants by HPLC or soluble luciferin-luciferase assay, thus it generally
      turns out to be laborious and inaccurate. We have engineered a chimeric plasma
      membrane-targeted luciferase that allows in vivo real-time imaging of
      extracellular ATP. With this novel probe we have measured the ATP concentration
      within the tumour microenvironment of several experimentally-induced tumours.
      CONCLUSIONS/SIGNIFICANCE: Our results show that ATP in the tumour interstitium is
      in the hundreds micromolar range, while it is basically undetectable in healthy
      tissues. Here we show that a chimeric plasma membrane-targeted luciferase allows
      in vivo detection of high extracellular ATP concentration at tumour sites. On the
      contrary, tumour-free tissues show undetectable extracellular ATP levels.
      Extracellular ATP may be crucial for the tumour not only as a stimulus for growth
      but also as a source of an immunosuppressive agent such as adenosine. Our
      approach offers a new tool for the investigation of the biochemical composition
      of tumour milieu and for development of novel therapies based on the modulation
      of extracellular purine-based signalling.

PMID- 18612416
TI  - RickA expression is not sufficient to promote actin-based motility of Rickettsia
      raoultii.
AB  - BACKGROUND: Rickettsia raoultii is a novel Rickettsia species recently isolated
      from Dermacentor ticks and classified within the spotted fever group (SFG). The
      inability of R. raoultii to spread within L929 cells suggests that this bacterium
      is unable to polymerize host cell actin, a property exhibited by all SFG
      rickettsiae except R. peacocki. This result led us to investigate if RickA, the
      protein thought to generate actin nucleation, was expressed within this
      rickettsia species. METHODOLOGY/PRINCIPAL FINDINGS: Amplification and sequencing
      of R. raoultii rickA showed that this gene encoded a putative 565 amino acid
      protein highly homologous to those found in other rickettsiae. Using
      immunofluorescence assays, we determined that the motility pattern (i.e.
      microcolonies or cell-to-cell spreading) of R. raoultii was different depending
      on the host cell line in which the bacteria replicated. In contrast, under the
      same experimental conditions, R. conorii shares the same phenotype both in L929
      and in Vero cells. Transmission electron microscopy analysis of infected cells
      showed that non-motile bacteria were free in the cytosol instead of enclosed in a
      vacuole. Moreover, western-blot analysis demonstrated that the defect of R.
      raoultii actin-based motility within L929 cells was not related to lower
      expression of RickA. CONCLUSION/SIGNIFICANCE: These results, together with
      previously published data about R. typhi, strongly suggest that another factor,
      apart from RickA, may be involved with be responsible for actin-based motility in
      bacteria from the Rickettsia genus.

PMID- 18612417
TI  - Lateral transfer of a lectin-like antifreeze protein gene in fishes.
AB  - Fishes living in icy seawater are usually protected from freezing by endogenous
      antifreeze proteins (AFPs) that bind to ice crystals and stop them from growing.
      The scattered distribution of five highly diverse AFP types across
      phylogenetically disparate fish species is puzzling. The appearance of radically
      different AFPs in closely related species has been attributed to the rapid,
      independent evolution of these proteins in response to natural selection caused
      by sea level glaciations within the last 20 million years. In at least one
      instance the same type of simple repetitive AFP has independently originated in
      two distant species by convergent evolution. But, the isolated occurrence of
      three very similar type II AFPs in three distantly related species (herring,
      smelt and sea raven) cannot be explained by this mechanism. These globular,
      lectin-like AFPs have a unique disulfide-bonding pattern, and share up to 85%
      identity in their amino acid sequences, with regions of even higher identity in
      their genes. A thorough search of current databases failed to find a homolog in
      any other species with greater than 40% amino acid sequence identity. Consistent
      with this result, genomic Southern blots showed the lectin-like AFP gene was
      absent from all other fish species tested. The remarkable conservation of both
      intron and exon sequences, the lack of correlation between evolutionary distance
      and mutation rate, and the pattern of silent vs non-silent codon changes make it
      unlikely that the gene for this AFP pre-existed but was lost from most branches
      of the teleost radiation. We propose instead that lateral gene transfer has
      resulted in the occurrence of the type II AFPs in herring, smelt and sea raven
      and allowed these species to survive in an otherwise lethal niche.

PMID- 18612418
TI  - Development of functional genomic tools in trematodes: RNA interference and
      luciferase reporter gene activity in Fasciola hepatica.
AB  - The growing availability of sequence information from diverse parasites through
      genomic and transcriptomic projects offer new opportunities for the
      identification of key mediators in the parasite-host interaction. Functional
      genomics approaches and methods for the manipulation of genes are essential tools
      for deciphering the roles of genes and to identify new intervention targets in
      parasites. Exciting advances in functional genomics for parasitic helminths are
      starting to occur, with transgene expression and RNA interference (RNAi) reported
      in several species of nematodes, but the area is still in its infancy in
      flatworms, with reports in just three species. While advancing in model
      organisms, there is a need to rapidly extend these technologies to other
      parasites responsible for several chronic diseases of humans and cattle. In order
      to extend these approaches to less well studied parasitic worms, we developed a
      test method for the presence of a viable RNAi pathway by silencing the exogenous
      reporter gene, firefly luciferase (fLUC). We established the method in the human
      blood fluke Schistosoma mansoni and then confirmed its utility in the liver fluke
      Fasciola hepatica. We transformed newly excysted juveniles of F. hepatica by
      electroporation with mRNA of fLUC and three hours later were able to detect
      luciferase enzyme activity, concentrated mainly in the digestive ceca.
      Subsequently, we tested the presence of an active RNAi pathway in F. hepatica by
      knocking down the exogenous luciferase activity by introduction into the
      transformed parasites of double-stranded RNA (dsRNA) specific for fLUC. In
      addition, we tested the RNAi pathway targeting an endogenous F. hepatica gene
      encoding leucine aminopeptidase (FhLAP), and observed a significant reduction in
      specific mRNA levels. In summary, these studies demonstrated the utility of RNAi
      targeting reporter fLUC as a reporter gene assay to establish the presence of an
      intact RNAi pathway in helminth parasites. These could facilitate the study of
      gene function and the identification of relevant targets for intervention in
      organisms that are by other means intractable. More specifically, these results
      open new perspectives for functional genomics of F. hepatica, which hopefully can
      lead to the development of new interventions for fascioliasis.

PMID- 18612419
TI  - Insight into microevolution of Yersinia pestis by clustered regularly interspaced
      short palindromic repeats.
AB  - BACKGROUND: Yersinia pestis, the pathogen of plague, has greatly influenced human
      history on a global scale. Clustered Regularly Interspaced Short Palindromic
      Repeat (CRISPR), an element participating in immunity against phages' invasion,
      is composed of short repeated sequences separated by unique spacers and provides
      the basis of the spoligotyping technology. In the present research, three CRISPR
      loci were analyzed in 125 strains of Y. pestis from 26 natural plague foci of
      China, the former Soviet Union and Mongolia were analyzed, for validating CRISPR
      based genotyping method and better understanding adaptive microevolution of Y.
      pestis. METHODOLOGY/PRINCIPAL FINDINGS: Using PCR amplification, sequencing and
      online data processing, a high degree of genetic diversity was revealed in all
      three CRISPR elements. The distribution of spacers and their arrays in Y. pestis
      strains is strongly region and focus-specific, allowing the construction of a
      hypothetic evolutionary model of Y. pestis. This model suggests transmission
      route of microtus strains that encircled Takla Makan Desert and ZhunGer Basin.
      Starting from Tadjikistan, one branch passed through the Kunlun Mountains, and
      moved to the Qinghai-Tibet Plateau. Another branch went north via the Pamirs
      Plateau, the Tianshan Mountains, the Altai Mountains and the Inner Mongolian
      Plateau. Other Y. pestis lineages might be originated from certain areas along
      those routes. CONCLUSIONS/SIGNIFICANCE: CRISPR can provide important information
      for genotyping and evolutionary research of bacteria, which will help to trace
      the source of outbreaks. The resulting data will make possible the development of
      very low cost and high-resolution assays for the systematic typing of any new
      isolate.

PMID- 18612420
TI  - Principles of glomerular organization in the human olfactory bulb--implications
      for odor processing.
AB  - Olfactory sensory neurons (OSN) in mice express only 1 of a possible 1,100 odor
      receptors (OR) and axons from OSNs expressing the same odor receptor converge
      into approximately 2 of the 1,800 glomeruli in each olfactory bulb (OB) in mice;
      this yields a convergence ratio that approximates 2:1, 2 glomeruli/OR. Because
      humans express only 350 intact ORs, we examined human OBs to determine if the
      glomerular convergence ratio of 2:1 established in mice was applicable to humans.
      Unexpectedly, the average number of human OB glomeruli is >5,500 yielding a
      convergence ratio of approximately 16:1. The data suggest that the initial coding
      of odor information in the human OB may differ from the models developed for
      rodents and that recruitment of additional glomeruli for subpopulations of ORs
      may contribute to more robust odor representation.

PMID- 18612421
TI  - Cognitive components of regularity processing in the auditory domain.
AB  - BACKGROUND: Music-syntactic irregularities often co-occur with the processing of
      physical irregularities. In this study we constructed chord-sequences such that
      perceived differences in the cognitive processing between regular and irregular
      chords could not be due to the sensory processing of acoustic factors like pitch
      repetition or pitch commonality (the major component of 'sensory dissonance').
      METHODOLOGY/PRINCIPAL FINDINGS: Two groups of subjects (musicians and
      nonmusicians) were investigated with electroencephalography (EEG). Irregular
      chords elicited an early right anterior negativity (ERAN) in the event-related
      brain potentials (ERPs). The ERAN had a latency of around 180 ms after the onset
      of the music-syntactically irregular chords, and had maximum amplitude values
      over right anterior electrode sites. CONCLUSIONS/SIGNIFICANCE: Because irregular
      chords were hardly detectable based on acoustical factors (such as pitch
      repetition and sensory dissonance), this ERAN effect reflects for the most part
      cognitive (not sensory) components of regularity-based, music-syntactic
      processing. Our study represents a methodological advance compared to previous
      ERP-studies investigating the neural processing of music-syntactically irregular
      chords.

PMID- 18612422
TI  - Phylogenetic detection of recombination with a Bayesian prior on the distance
      between trees.
AB  - Genomic regions participating in recombination events may support distinct
      topologies, and phylogenetic analyses should incorporate this heterogeneity.
      Existing phylogenetic methods for recombination detection are challenged by the
      enormous number of possible topologies, even for a moderate number of taxa. If,
      however, the detection analysis is conducted independently between each putative
      recombinant sequence and a set of reference parentals, potential recombinations
      between the recombinants are neglected. In this context, a recombination hotspot
      can be inferred in phylogenetic analyses if we observe several consecutive
      breakpoints. We developed a distance measure between unrooted topologies that
      closely resembles the number of recombinations. By introducing a prior
      distribution on these recombination distances, a Bayesian hierarchical model was
      devised to detect phylogenetic inconsistencies occurring due to recombinations.
      This model relaxes the assumption of known parental sequences, still common in
      HIV analysis, allowing the entire dataset to be analyzed at once. On simulated
      datasets with up to 16 taxa, our method correctly detected recombination
      breakpoints and the number of recombination events for each breakpoint. The
      procedure is robust to rate and transitionratiotransversion heterogeneities for
      simulations with and without recombination. This recombination distance is
      related to recombination hotspots. Applying this procedure to a genomic HIV-1
      dataset, we found evidence for hotspots and de novo recombination.

PMID- 18612423
TI  - Phase locking induces scale-free topologies in networks of coupled oscillators.
AB  - An initial unsynchronized ensemble of networking phase oscillators is further
      subjected to a growing process where a set of forcing oscillators, each one of
      them following the dynamics of a frequency pacemaker, are added to the pristine
      graph. Linking rules based on dynamical criteria are followed in the attachment
      process to force phase locking of the network with the external pacemaker. We
      show that the eventual locking occurs in correspondence to the arousal of a scale
      free degree distribution in the original graph.

PMID- 18612424
TI  - Adaptation of Saccharomyces cerevisiae cells to high ethanol concentration and
      changes in fatty acid composition of membrane and cell size.
AB  - BACKGROUND: Microorganisms can adapt to perturbations of the surrounding
      environment to grow. To analyze the adaptation process of the yeast Saccharomyces
      cerevisiae to a high ethanol concentration, repetitive cultivation was performed
      with a stepwise increase in the ethanol concentration in the culture medium.
      METHODOLOGY/PRINCIPAL FINDINGS: First, a laboratory strain of S. cerevisiae was
      cultivated in medium containing a low ethanol concentration, followed by
      repetitive cultivations. Then, the strain repeatedly cultivated in the low
      ethanol concentration was transferred to medium containing a high ethanol
      concentration and cultivated repeatedly in the same high-ethanol-concentration
      medium. When subjected to a stepwise increase in ethanol concentration with the
      repetitive cultivations, the yeast cells adapted to the high ethanol
      concentration; the specific growth rate of the adapted yeast strain did not
      decrease during repetitive cultivation in the medium containing the same ethanol
      concentration, while that of the non-adapted strain decreased during repetitive
      cultivation. A comparison of the fatty acid composition of the cell membrane
      showed that the contents in oleic acid (C(18:1)) in ethanol-adapted and non
      adapted strains were similar, but the content of palmitic acid (C(16:0)) in the
      ethanol-adapted strains was lower than that in the non-adapted strain in media
      containing ethanol. Moreover, microscopic observation showed that the mother
      cells of the adapted yeast were significantly larger than those of the non
      adapted strain. CONCLUSIONS: Our results suggest that activity of cell growth
      defined by specific growth rate of the yeast cells adapted to stepwise increase
      in ethanol concentration did not decrease during repetitive cultivation in high
      ethanol-concentration medium. Moreover, fatty acid content of cell membrane and
      the size of ethanol-adapted yeast cells were changed during adaptation process.
      Those might be the typical phenotypes of yeast cells adapted to high ethanol
      concentration. In addition, the difference in sizes of the mother cell between
      the non-adapted and ethanol strains suggests that the cell size, cell cycle and
      adaptation to ethanol are thought to be closely correlated.

PMID- 18612425
TI  - A three-way comparison of tuberculin skin testing, QuantiFERON-TB gold and T
      SPOT.TB in children.
AB  - BACKGROUND: There are limited data comparing the performance of the two
      commercially available interferon gamma (IFN-gamma) release assays (IGRAs) for
      the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold
      In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at
      risk for latent TB infection or TB disease. METHODS AND FINDINGS: The results of
      both IGRAs were compared with diagnosis assigned by TST-based criteria and
      assessed in relation to TB contact history. Results from the TST and at least one
      assay were available for 96 of 100 children. Agreement between QFT-IT and T
      SPOT.TB was high (93% agreement, kappa = 0.83). QFT-IT and T-SPOT.TB tests were
      positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There
      was moderate agreement between TST and either QFT-IT (75%, kappa = 0.50) or T
      SPOT.TB (75%, kappa = 0.51). Among 38 children with TST-defined latent TB
      infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39%
      respectively. Three TST-negative children were positive by at least one IGRA.
      Children with a TB contact were more likely than children without a TB contact to
      have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR
      1.4). Multivariate linear regression analysis showed that the magnitude of both
      TST induration and IGRA IFN-gamma responses was significantly influenced by TB
      contact history, but only the TST was influenced by age. CONCLUSIONS: Although a
      high level of agreement between the IGRAs was observed, they are commonly
      discordant with the TST. The correct interpretation of a negative assay in a
      child with a positive skin test in clinical practice remains challenging and
      highlights the need for longitudinal studies to determine the negative predictive
      value of IGRAs.

PMID- 18612426
TI  - Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25
      formulated with montanide ISA 51.
AB  - BACKGROUND: Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria
      parasites P. falciparum and P. vivax, respectively, are leading candidates for
      vaccines preventing malaria transmission by mosquitoes. This single blinded, dose
      escalating, controlled Phase 1 study assessed the safety and immunogenicity of
      recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil
      emulsion. METHODOLOGY/PRINCIPAL FINDINGS: The trial was conducted at The Johns
      Hopkins Center for Immunization Research, Washington DC, USA, between May 16,
      2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non
      pregnant female volunteers into 1 group to receive adjuvant control and 6 groups
      to receive escalating doses of the vaccines. Due to unexpected reactogenicity,
      the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3
      groups of 10 volunteers each were immunized with 5 microg of Pfs25/ISA 51, 5
      microg of Pvs25/ISA 51, or 20 microg of Pvs25/ISA 51, respectively. A fourth
      group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local
      reactogenicity was observed. Systemic adverse events included two cases of
      erythema nodosum considered to be probably related to the combination of the
      antigen and the adjuvant. Significant antibody responses were detected in
      volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti
      Pfs25 levels correlated with transmission blocking activity.
      CONCLUSION/SIGNIFICANCE: It is feasible to induce transmission blocking immunity
      in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly
      reactogenic for further development. This is the first report that the
      formulation is associated with systemic adverse events including erythema
      nodosum. TRIAL REGISTRATION: ClinicalTrials.gov NCT00295581.

PMID- 18612427
TI  - Nonsense-mediated mRNA decay impacts MSI-driven carcinogenesis and anti-tumor
      immunity in colorectal cancers.
AB  - Nonsense-mediated mRNA Decay (NMD) degrades mutant mRNAs containing premature
      termination codon (PTC-mRNAs). Here we evaluate the consequence of NMD activity
      in colorectal cancers (CRCs) showing microsatellite instability (MSI) whose
      progression is associated with the accumulation of PTC-mRNAs encoding immunogenic
      proteins due to frameshift mutations in coding repeat sequences. Inhibition of
      UPF1, one of the major NMD factors, was achieved by siRNA in the HCT116 MSI CRC
      cell line and the resulting changes in gene expression were studied using
      expression microarrays. The impact of NMD activity was also investigated in
      primary MSI CRCs by quantifying the expression of several mRNAs relative to their
      mutational status and to endogenous UPF1 and UPF2 expression. Host immunity
      developed against MSI cancer cells was appreciated by quantifying the number of
      CD3epsilon-positive tumor-infiltrating lymphocytes (TILs). UPF1 silencing led to
      the up-regulation of 1251 genes in HCT116, among which a proportion of them (i.e.
      38%) significantly higher than expected by chance contained a coding
      microsatellite (P<2x10(-16)). In MSI primary CRCs, UPF1 was significantly over
      expressed compared to normal adjacent mucosa (P<0.002). Our data provided
      evidence for differential decay of PTC-mRNAs compared to wild-type that was
      positively correlated to UPF1 endogenous expression level (P = 0.02). A negative
      effect of UPF1 and UPF2 expression on the host's anti-tumor response was observed
      (P<0.01). Overall, our results show that NMD deeply influences MSI-driven
      tumorigenesis at the molecular level and indicate a functional negative impact of
      this system on anti-tumor immunity whose intensity has been recurrently shown to
      be an independent factor of favorable outcome in CRCs.

PMID- 18612429
TI  - Professional and home-made face masks reduce exposure to respiratory infections
      among the general population.
AB  - BACKGROUND: Governments are preparing for a potential influenza pandemic.
      Therefore they need data to assess the possible impact of interventions. Face
      masks worn by the general population could be an accessible and affordable
      intervention, if effective when worn under routine circumstances. METHODOLOGY: We
      assessed transmission reduction potential provided by personal respirators,
      surgical masks and home-made masks when worn during a variety of activities by
      healthy volunteers and a simulated patient. PRINCIPAL FINDINGS: All types of
      masks reduced aerosol exposure, relatively stable over time, unaffected by
      duration of wear or type of activity, but with a high degree of individual
      variation. Personal respirators were more efficient than surgical masks, which
      were more efficient than home-made masks. Regardless of mask type, children were
      less well protected. Outward protection (mask wearing by a mechanical head) was
      less effective than inward protection (mask wearing by healthy volunteers).
      CONCLUSIONS/SIGNIFICANCE: Any type of general mask use is likely to decrease
      viral exposure and infection risk on a population level, in spite of imperfect
      fit and imperfect adherence, personal respirators providing most protection.
      Masks worn by patients may not offer as great a degree of protection against
      aerosol transmission.

PMID- 18612428
TI  - Pharmacologic stem cell based intervention as a new approach to osteoporosis
      treatment in rodents.
AB  - BACKGROUND: Osteoporosis is the most prevalent skeletal disorder, characterized
      by a low bone mineral density (BMD) and bone structural deterioration, leading to
      bone fragility fractures. Accelerated bone resorption by osteoclasts has been
      established as a principal mechanism in osteoporosis. However, recent
      experimental evidences suggest that inappropriate apoptosis of
      osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone
      remodeling as occurs in osteoporosis. The aim of this study is to examine whether
      aspirin, which has been reported as an effective drug improving bone mineral
      density in human epidemiology studies, regulates the balance between bone
      resorption and bone formation at stem cell levels. METHODS AND FINDINGS: We found
      that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a
      crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studies
      revealed that T cell-mediated BMMSC impairment was mainly attributed to the
      apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using
      pharmacologic stem cell based intervention as an approach for osteoporosis
      treatment, we selected ovariectomy (OVX)-induced osteoporosis mouse model to
      examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis.
      We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC
      apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of
      BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX
      mice, leading to ameliorating bone density. CONCLUSION: Our findings have
      revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC
      apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell
      based intervention by aspirin may be a new alternative in osteoporosis treatment
      including activated osteoblasts and inhibited osteoclasts.

PMID- 18612430
TI  - Waist circumference and body mass index as predictors of health care costs.
AB  - BACKGROUND: In the present study we analyze the relationship between body mass
      index (BMI) and waist circumference (WC) and future health care costs. On the
      basis of the relation between these anthropometric measures and mortality, we
      hypothesized that for all levels of BMI increased WC implies added future health
      care costs (Hypothesis 1) and for given levels of WC increased BMI entails
      reduced future health care costs (Hypothesis 2). We furthermore assessed whether
      a combination of the two measures predicts health care costs better than either
      individual measure. RESEARCH METHODOLOGY/PRINCIPAL FINDINGS: Data were obtained
      from the Danish prospective cohort study Diet, Cancer and Health. The population
      includes 15,334 men and 16,506 women 50 to 64 years old recruited in 1996 to
      1997. The relationship between future health care costs and BMI and WC in
      combination was analyzed by use of categorized and continuous analyses. The
      analysis confirms Hypothesis 1, reflecting that an increased level of abdominal
      fat for a given BMI gives higher health care costs. Hypothesis 2, that BMI had a
      protective effect for a given WC, was only confirmed in the continuous analysis
      and for a subgroup of women (BMI<30 kg/m(2) and WC <88 cm). The relative
      magnitude of the estimates supports that the regressions including WC as an
      explanatory factor provide the best fit to the data. CONCLUSION: The study showed
      that WC for given levels of BMI predicts increased health costs, whereas BMI for
      given WC did not predict health costs except for a lower cost in non-obese women
      with normal WC. Combining WC and BMI does not give a better prediction of costs
      than WC alone.

PMID- 18612431
TI  - EEF2 analysis challenges the monophyly of Archaeplastida and Chromalveolata.
AB  - BACKGROUND: Classification of eukaryotes provides a fundamental phylogenetic
      framework for ecological, medical, and industrial research. In recent years
      eukaryotes have been classified into six major supergroups: Amoebozoa,
      Archaeplastida, Chromalveolata, Excavata, Opisthokonta, and Rhizaria. According
      to this supergroup classification, Archaeplastida and Chromalveolata each arose
      from a single plastid-generating endosymbiotic event involving a cyanobacterium
      (Archaeplastida) or red alga (Chromalveolata). Although the plastids within
      members of the Archaeplastida and Chromalveolata share some features, no
      nucleocytoplasmic synapomorphies supporting these supergroups are currently
      known. METHODOLOGY/PRINCIPAL FINDINGS: This study was designed to test the
      validity of the Archaeplastida and Chromalveolata through the analysis of nucleus
      encoded eukaryotic translation elongation factor 2 (EEF2) and cytosolic heat
      shock protein of 70 kDa (HSP70) sequences generated from the glaucophyte
      Cyanophora paradoxa, the cryptophytes Goniomonas truncata and Guillardia theta,
      the katablepharid Leucocryptos marina, the rhizarian Thaumatomonas sp. and the
      green alga Mesostigma viride. The HSP70 phylogeny was largely unresolved except
      for certain well-established groups. In contrast, EEF2 phylogeny recovered many
      well-established eukaryotic groups and, most interestingly, revealed a well
      supported clade composed of cryptophytes, katablepharids, haptophytes,
      rhodophytes, and Viridiplantae (green algae and land plants). This clade is
      further supported by the presence of a two amino acid signature within EEF2,
      which appears to have arisen from amino acid replacement before the common origin
      of these eukaryotic groups. CONCLUSIONS/SIGNIFICANCE: Our EEF2 analysis strongly
      refutes the monophyly of the Archaeplastida and the Chromalveolata, adding to a
      growing body of evidence that limits the utility of these supergroups. In view of
      EEF2 phylogeny and other morphological evidence, we discuss the possibility of an
      alternative eukaryotic supergroup.

PMID- 18612432
TI  - The tumorigenicity of mouse embryonic stem cells and in vitro differentiated
      neuronal cells is controlled by the recipients' immune response.
AB  - Embryonic stem (ES) cells have the potential to differentiate into all cell types
      and are considered as a valuable source of cells for transplantation therapies. A
      critical issue, however, is the risk of teratoma formation after transplantation.
      The effect of the immune response on the tumorigenicity of transplanted cells is
      poorly understood. We have systematically compared the tumorigenicity of mouse ES
      cells and in vitro differentiated neuronal cells in various recipients.
      Subcutaneous injection of 1x10(6) ES or differentiated cells into syngeneic or
      allogeneic immunodeficient mice resulted in teratomas in about 95% of the
      recipients. Both cell types did not give rise to tumors in immunocompetent
      allogeneic mice or xenogeneic rats. However, in 61% of cyclosporine A-treated
      rats teratomas developed after injection of differentiated cells.
      Undifferentiated ES cells did not give rise to tumors in these rats. ES cells
      turned out to be highly susceptible to killing by rat natural killer (NK) cells
      due to the expression of ligands of the activating NK receptor NKG2D on ES cells.
      These ligands were down-regulated on differentiated cells. The activity of NK
      cells which is not suppressed by cyclosporine A might contribute to the
      prevention of teratomas after injection of ES cells but not after inoculation of
      differentiated cells. These findings clearly point to the importance of the
      immune response in this process. Interestingly, the differentiated cells must
      contain a tumorigenic cell population that is not present among ES cells and
      which might be resistant to NK cell-mediated killing.

PMID- 18612433
TI  - Galectin-4 controls intestinal inflammation by selective regulation of peripheral
      and mucosal T cell apoptosis and cell cycle.
AB  - Galectin-4 is a carbohydrate-binding protein belonging to the galectin family.
      Here we provide novel evidence that galectin-4 is selectively expressed and
      secreted by intestinal epithelial cells and binds potently to activated
      peripheral and mucosal lamina propria T-cells at the CD3 epitope. The
      carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully
      functional and inhibited T cell activation, cycling and expansion. Galectin-4
      induced apoptosis of activated peripheral and mucosal lamina propria T cells via
      calpain-, but not caspase-dependent, pathways. Providing further evidence for its
      important role in regulating T cell function, galectin-4 blockade by antisense
      oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore,
      in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL
      17. In a model of experimental colitis, galectin-4 ameliorated mucosal
      inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of
      pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role
      in the intestine and assign a novel role of this protein in controlling
      intestinal inflammation by a selective induction of T cell apoptosis and cell
      cycle restriction. Conclusively, after defining its biological role, we propose
      Galectin-4 is a novel anti-inflammatory agent that could be therapeutically
      effective in diseases with a disturbed T cell expansion and apoptosis such as
      inflammatory bowel disease.

PMID- 18612434
TI  - Oct-4 expression maintained cancer stem-like properties in lung cancer-derived
      CD133-positive cells.
AB  - CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered
      to be an important marker that represents the subset population of cancer stem
      like cells. Herein we report the isolation of CD133-positive cells (LC-CD133(+))
      and CD133-negative cells (LC-CD133(-)) from tissue samples of ten patients with
      non-small cell lung cancer (LC) and five LC cell lines. LC-CD133(+) displayed
      higher Oct-4 expressions with the ability to self-renew and may represent a
      reservoir with proliferative potential for generating lung cancer cells.
      Furthermore, LC-CD133(+), unlike LC-CD133(-), highly co-expressed the multiple
      drug-resistant marker ABCG2 and showed significant resistance to chemotherapy
      agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and
      radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can
      specifically block the capability of LC-CD133(+) to form spheres and can further
      facilitate LC-CD133(+) to differentiate into LC-CD133(-). In addition, knock-down
      of Oct-4 expression in LC-CD133(+) can significantly inhibit the abilities of
      tumor invasion and colony formation, and increase apoptotic activities of caspase
      3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies
      further confirm that the treatment effect of chemoradiotherapy for LC-CD133(+)
      can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated
      that Oct-4 expression plays a crucial role in maintaining the self-renewing,
      cancer stem-like, and chemoradioresistant properties of LC-CD133(+). Future
      research is warranted regarding the up-regulated expression of Oct-4 in LC
      CD133(+) and malignant lung cancer.

PMID- 18612435
TI  - Probing the dynamics of identified neurons with a data-driven modeling approach.
AB  - In controlling animal behavior the nervous system has to perform within the
      operational limits set by the requirements of each specific behavior. The
      implications for the corresponding range of suitable network, single neuron, and
      ion channel properties have remained elusive. In this article we approach the
      question of how well-constrained properties of neuronal systems may be on the
      neuronal level. We used large data sets of the activity of isolated invertebrate
      identified cells and built an accurate conductance-based model for this cell type
      using customized automated parameter estimation techniques. By direct inspection
      of the data we found that the variability of the neurons is larger when they are
      isolated from the circuit than when in the intact system. Furthermore, the
      responses of the neurons to perturbations appear to be more consistent than their
      autonomous behavior under stationary conditions. In the developed model, the
      constraints on different parameters that enforce appropriate model dynamics vary
      widely from some very tightly controlled parameters to others that are almost
      arbitrary. The model also allows predictions for the effect of blocking selected
      ionic currents and to prove that the origin of irregular dynamics in the neuron
      model is proper chaoticity and that this chaoticity is typical in an appropriate
      sense. Our results indicate that data driven models are useful tools for the in
      depth analysis of neuronal dynamics. The better consistency of responses to
      perturbations, in the real neurons as well as in the model, suggests a paradigm
      shift away from measuring autonomous dynamics alone towards protocols of
      controlled perturbations. Our predictions for the impact of channel blockers on
      the neuronal dynamics and the proof of chaoticity underscore the wide scope of
      our approach.

PMID- 18612436
TI  - Comparative analysis of viral gene expression programs during poxvirus infection:
      a transcriptional map of the vaccinia and monkeypox genomes.
AB  - BACKGROUND: Poxviruses engage in a complex and intricate dialogue with host cells
      as part of their strategy for replication. However, relatively little molecular
      detail is available with which to understand the mechanisms behind this dialogue.
      METHODOLOGY/PRINCIPAL FINDINGS: We designed a specialized microarray that
      contains probes specific to all predicted ORFs in the Monkeypox Zaire (MPXV) and
      Vaccinia Western Reserve (VACV) genomes, as well as >18,000 human genes, and used
      this tool to characterize MPXV and VACV gene expression responses in vitro during
      the course of primary infection of human monocytes, primary human fibroblasts and
      HeLa cells. The two viral transcriptomes show distinct features of temporal
      regulation and species-specific gene expression, and provide an early foundation
      for understanding global gene expression responses during poxvirus infection.
      CONCLUSIONS/SIGNIFICANCE: The results provide a temporal map of the transcriptome
      of each virus during infection, enabling us to compare viral gene expression
      across species, and classify expression patterns of previously uncharacterized
      ORFs.

PMID- 18612437
TI  - Knowledge, awareness and practices regarding dengue fever among the adult
      population of dengue hit cosmopolitan.
AB  - BACKGROUND: The World health Organization (WHO) declares dengue and dengue
      hemorrhagic fever to be endemic in South Asia. Despite the magnitude of problem,
      no documented evidence exists in Pakistan which reveals the awareness and
      practices of the country's adult population regarding dengue fever, its spread,
      symptoms, treatment and prevention. This study was conducted to assess the level
      of knowledge, attitudes and practices regarding dengue fever in people visiting
      tertiary care hospitals in Karachi, Pakistan. METHODS: A cross-sectional pilot
      study was conducted among people visiting tertiary care hospitals in Karachi.
      Through convenience sampling, a pre-tested and structured questionnaire was
      administered through a face-to-face unprompted interview with 447 visitors.
      Knowledge was recorded on a scale of 1-3. RESULTS: About 89.9% of individuals
      interviewed had heard of dengue fever. Sufficient knowledge about dengue was
      found to be in 38.5% of the sample, with 66% of these in Aga Khan University
      Hospital and 33% in Civil Hospital Karachi. Literate individuals were relatively
      more well-informed about dengue fever as compared to the illiterate people
      (p<0.001). Knowledge based upon preventive measures was found to be predominantly
      focused towards prevention of mosquito bites (78.3%) rather than eradication of
      mosquito population (17.3%). Use of anti-mosquito spray was the most prevalent
      (48.1%) preventive measure. Television was considered as the most important and
      useful source of information on the disease. CONCLUSION: Adult population of
      Karachi has adequate knowledge related to the disease 'dengue' on isolated
      aspects, but the overall prevalence of 'sufficient knowledge' based on our
      criteria is poor. We demonstrated adequate prevalence of preventive practices
      against the disease. Further studies correlating the association between
      knowledge and its effectiveness against dengue will be helpful in demonstrating
      the implications of awareness campaigns.

PMID- 18612438
TI  - Acute Ortner's syndrome arising from ductus arteriosus aneurysm.

PMID- 18612439
TI  - Statins improve human coronary atherosclerotic plaque morphology.
AB  - Statin treatment markedly reduces the incidence of acute coronary events in
      patients with coronary atherosclerosis. Although imaging studies have indirectly
      shown the beneficial effects of statins on plaque morphology, there has to our
      knowledge been no reported histologic comparison of the morphology of coronary
      plaque in statin-treated versus untreated patients who had substantial coronary
      artery atherosclerosis. We retrospectively studied arterial sections from the
      native hearts of patients who had experienced end-stage ischemic heart disease
      and subsequent cardiac transplantation. Of 44 qualified patients, 33 study
      patients had received pre-transplantation statin therapy, and 11 control patients
      had not. Pathologic examination of each explanted heart confirmed coronary artery
      disease and previous myocardial infarction in all patients. Diabetes mellitus was
      more prevalent in the study group. The groups were similar in levels of total and
      low-density lipoprotein cholesterol, and in the available number of arterial
      cross-sections per patient. All patients had plaques. High-grade lesions were
      found in 66.3% of cross-sections in the control group, and in 34.6% in the study
      group (P=0.011). Conversely, the degree of inflammation was markedly lower in the
      study group: low-grade fibrous plaques occurred in 45.7% of cross-sections in the
      study group, versus 11.3% in the control group (P=0.006). The study group had
      significantly fewer high-grade plaques and more fibrous plaques than did the
      control group at the time of transplantation. Our findings show that statin
      therapy substantially enhances plaque stabilization. We further suggest that
      reduction of plaque inflammation is an important aspect of this stabilization.

PMID- 18612441
TI  - Severe calcific chronic constrictive tuberculous pericarditis.

PMID- 18612440
TI  - Diagnostic accuracy of N-terminal pro-brain natriuretic peptide in the evaluation
      of postoperative left ventricular diastolic dysfunction.
AB  - We compared the diagnostic accuracy of N-terminal prohormone brain natriuretic
      peptide (NT-proBNP) with that of echocardiography in the evaluation of left
      ventricular diastolic dysfunction after coronary artery bypass grafting. Thirty
      patients were studied prospectively. Patients who had recent myocardial
      infarction, unstable angina pectoris, or low ejection fraction with systolic
      dysfunction were excluded. Two blood samples were obtained: before anesthetic
      induction and on the 7th postoperative day. Levels of NT-proBNP were measured by
      electrochemiluminescence immunoassay. Comprehensive echocardiographic Doppler
      examinations were performed on admission and on the 7th postoperative day.
      Relationships between NT-proBNP levels and echocardiographic indices were
      evaluated by correlation, multiple linear regression, and receiver-operating
      characteristic curve analysis. There were significant and correlated worsenings
      in diastolic stage as determined both by echocardiographic indices and NT-proBNP
      levels. Early transmitral-to-early diastolic annular velocity ratio (E/Ea) was
      found to correlate with both NT-proBNP and postoperative diastolic functional
      stage (r=0.78, P <0.001). Mitral E/Ea was significantly more sensitive than were
      NT-proBNP levels in predicting diastolic functional stage. The area under the
      receiver-operating characteristic curve for NT-proBNP was significantly lower
      than that of mitral E/Ea (mean difference, 0.12; P=0.024). The NT-proBNP had
      87.5% sensitivity and 55% specificity, whereas E/Ea had 87.5% sensitivity and
      86.4% specificity. Plasma NT-proBNP levels are significantly related to mitral
      E/Ea ratio, which is a predictor of diastolic stage. Therefore, elevated NT
      proBNP levels may indicate the time for a Doppler echocardiographic evaluation
      and identify a subgroup of patients at high risk who need closer monitoring
      during the early postoperative period.

PMID- 18612442
TI  - Biatrial myxoma and cerebral ischemia successfully treated with intravenous
      thrombolytic therapy and surgical resection.
AB  - We report what we believe is the 1st case in the medical literature in which an
      intravenous thrombolytic agent was used successfully--without massive
      intracranial bleeding--to treat acute stroke induced by atrial myxoma. Our
      patient, who had biatrial myxomas with a dual blood supply from the right
      coronary artery, presented with cerebral ischemia. Transesophageal
      echocardiography was essential in clarifying the diagnosis and in helping to
      direct surgical treatment.

PMID- 18612443
TI  - New use of teflon to reduce bleeding in modified bentall operation.
AB  - We analyzed the postoperative short- and mid-term outcomes of a series of
      patients with annuloaortic ectasia who underwent a modified Bentall operation in
      our clinic from September 2000 through March 2006. The study included 44
      patients. Their average age was 53.4 +/- 14.1 years. The underlying disease was
      degenerative aortic aneurysm in 42 patients (95.5%) and acute aortic dissection
      in 2 patients (4.5%). Six patients (13.6%) had Marfan phenotype. Aortic
      insufficiency was moderate in 30 patients (68.2%) and severe in 14 patients
      (31.8%). In our modification of the Bentall technique, we completed the resection
      of the aortic root while leaving 5 to 10 mm of native aortic wall tissue to
      support the anastomosis. A long piece of Teflon felt (width, 0.5-1 cm) was laid
      on the annulus, and nonpledgeted 2-0 polyester sutures were passed in turn
      through the Teflon felt, the preserved aortic tissue, and the aortic annulus. A
      thin piece of Teflon felt was also used in the coronary artery reimplantation
      sites. Fibrin glue was routinely applied to all anastomoses. There were no
      intraoperative deaths. One patient died in the hospital after surgery for acute
      type I aortic dissection. Another patient died 1 year after the operation from
      prosthetic-valve endocarditis. No patient required surgical correction of
      excessive postoperative bleeding. Kaplan-Meier curves showed overall survival of
      0.94 (95% confidence intervals, 0.9-0.99). We consider our approach an easy,
      effective way to minimize bleeding from the anastomoses and at the aortic root--a
      common challenge in aortic surgery.

PMID- 18612444
TI  - Detection of Helicobacter pylori DNA in aortic and left internal mammary artery
      biopsies.
AB  - We investigated the relationship between acute coronary ischemia and the presence
      of Helicobacter pylori DNA in aortic regions that were absent macroscopic
      atheromatous plaques. The study group (Group 1) consisted of 42 patients who
      underwent coronary artery bypass grafting. Biopsy samples were obtained from 2
      different locations: from regions of the aorta that were free (macroscopically)
      of atheromatous plaque (Group 1A), and from the internal mammary artery (Group
      1B). The control group (Group 2) of 10 patients who had no atherosclerotic
      vascular disease provided aortic tissue samples for comparison. The real-time
      polymerase chain reaction method was used to detect H. pylori DNA in all biopsy
      samples. Eleven of 42 aortic tissue samples (26%) in Group 1A were positive for
      H. pylori DNA. Neither biopsies from the left internal mammary arteries of those
      patients nor biopsies from the aortas of the control group (Group 2) were
      positive for H. pylori DNA. There was a statistically significant difference
      between 1A and 1B in terms of H. pylori positivity (P=0.001). In Group 1 as a
      whole, acute coronary ischemia was more prevalent in the H. pylori-positive
      patients than in the H. pylori-negative patients (P=0.001). To our knowledge,
      this is the 1st study to investigate the detection of H. pylori DNA in aortic
      biopsy samples that are macroscopically free of atheromatous plaque. Such
      detection in patients who have atherosclerotic coronary artery disease could be
      an important indication of the role of microorganisms in the pathogenesis of
      atherosclerosis.

PMID- 18612445
TI  - Ectopic origin of left coronary ostium from left ventricle, with occlusive
      membrane: a previously unreported anomaly, with an embryologic interpretation.
AB  - Congenital atresia of the left main coronary artery, a condition in which the
      left main trunk is developed but has been occluded since birth, is a rare
      coronary anomaly. Herein, we describe this anomaly's association with a
      subannular location of an obliterated left main ostium in a patient with a
      bicuspid aortic valve and severe aortic stenosis. The patient underwent
      successful surgery. We discuss the embryologic implications of congenital atresia
      of the left main coronary artery, in view of the exceptional anatomic features of
      this condition. To our knowledge, this is the 1st report of a left coronary
      artery that was found to arise from the left ventricle.

PMID- 18612446
TI  - Cardiologists' and emergency physicians' perspectives on and knowledge of
      reperfusion guidelines pertaining to ST-segment-elevation myocardial infarction.
AB  - We sought to determine U.S. physicians' knowledge and perspectives regarding the
      2004 American College of Cardiology/American Heart Association guidelines for
      management of patients who have ST-segment-elevation myocardial infarction
      (STEMI). We invited 45,998 physicians from the American Medical Association's
      roster to take an Internet survey of U.S. cardiologists and emergency physicians
      who were hospital-based or who had hospital-admitting privileges. To represent
      individual and combined populations, data were weighted on the basis of years in
      practice, sex, and geographic region. Of 505 cardiologists and 509 emergency
      physicians who completed the survey, 90% worked in an urban or suburban setting
      and 82% at hospitals with a cardiac catheterization laboratory. Sampling error
      was +/-3.4%. Most respondents (61%) believed that overall myocardial infarction
      treatment needed a "great deal" or "fair amount" of improvement; 24% were
      "somewhat" or "not at all" familiar with the guidelines. Although 84% knew the
      recommended STEMI treatments for a patient who presents within 3 hours of symptom
      onset without contraindications to reperfusion or delay to invasive treatment,
      only 11% knew that there is no preferred approach. If percutaneous coronary
      intervention proved impossible within 90 minutes of presentation, 21% reported
      that eligible patients--assuming early presentation, confirmed STEMI diagnosis,
      and no high-risk STEMI or contraindications to fibrinolysis--would "rarely" or
      "never" receive guideline-recommended fibrinolysis. Many cardiologists and
      emergency physicians are unfamiliar with the guidelines and with the uncertainty
      that surrounds therapeutic approaches, which suggests the need for increased
      education on effective treatments to expedite myocardial reperfusion in STEMI.

PMID- 18612447
TI  - "Chronic" dishonesty in medicine?

PMID- 18612448
TI  - The TandemHeart as a bridge to a long-term axial-flow left ventricular assist
      device (bridge to bridge).
AB  - End-stage heart-failure patients in acute refractory cardiogenic shock with multi
      organ dysfunction require aggressive medical therapy that includes inotropic
      support. Historically, the intra-aortic balloon pump was the last option for
      patients who were dying of acute cardiogenic shock. Short-term extracorporeal
      pulsatile or nonpulsatile cardiac assist devices or extracorporeal membrane
      oxygenation offered further treatment options; however, these therapies required
      invasive surgical procedures. Patients in this high-risk group had increased
      mortality rates from major procedures that required cardiopulmonary bypass. We
      used the TandemHeart, a percutaneously implanted device for short-term cardiac
      assistance, to lower the risk of death and improve hemodynamic performance and
      end-organ perfusion before implanting long-term assist devices in selected
      patients with signs of profound cardiogenic shock. Nine end-stage heart-failure
      patients (mean age, 37.7 yr) in acute refractory hemodynamic decompensation
      received a percutaneously implanted TandemHeart pump as a bridge to an
      implantable axial-flow pump. To determine the relative risk for these patients,
      prognostic scores were calculated before and after insertion of the TandemHeart.
      Percutaneous support times ranged from 1 to 22 days (mean, 5.9 d). The mean
      cardiac index before support, 1.02 L/(min.m2) (range, 0.0-1.8 L/[min.m2]) (0.0
      L/[min.m2] implies active cardiopulmonary resuscitation), improved to 2.97
      L/(min.m2) (range, 2.2-4.0 L/[min.m2]) during support. Three patients underwent
      successful cardiac transplantation; 5 are currently supported by axial-flow
      pumps; and 1 died of complications unrelated to the axial-flow pump, after 587
      days. End-organ function and overall condition improved uniformly in our
      patients, thus decreasing the preoperative risk factors for implantation of the
      long-term device.

PMID- 18612450
TI  - Giant right femoral pseudoaneurysm diagnosed 7 years after cardiac
      catheterization.

PMID- 18612452
TI  - Vascular ring: tracheoesophageal compression associated with symmetrical double
      aortic arch.

PMID- 18612451
TI  - Devices in heart failure: potential methods for device-based monitoring of
      congestive heart failure.
AB  - Congestive heart failure has long been one of the most serious medical conditions
      in the United States; in fact, in the United States alone, heart failure accounts
      for 6.5 million days of hospitalization each year. One important goal of heart
      failure therapy is to inhibit the progression of congestive heart failure through
      pharmacologic and device-based therapies. Therefore, there have been efforts to
      develop device-based therapies aimed at improving cardiac reserve and optimizing
      pump function to meet metabolic requirements. The course of congestive heart
      failure is often worsened by other conditions, including new-onset arrhythmias,
      ischemia and infarction, valvulopathy, decompensation, end-organ damage, and
      therapeutic refractoriness, that have an impact on outcomes. The onset of such
      conditions is sometimes heralded by subtle pathophysiologic changes, and the
      timely identification of these changes may promote the use of preventive
      measures. Consequently, device-based methods could in the future have an
      important role in the timely identification of the subtle pathophysiologic
      changes associated with congestive heart failure.

PMID- 18612453
TI  - Midwife.

PMID- 18612454
TI  - Combined cardiac-neurosurgical treatment of acute aortic dissection, stroke, and
      coma.
AB  - Coma or stroke with secondary brain malperfusion is usually considered a strong
      contraindication for emergent surgical treatment of acute aortic dissection.
      Herein, we present the case of a 30-year-old woman who presented with sudden left
      hemiplegia and level-7 coma on the Glasgow Coma Scale. Transthoracic
      echocardiography showed type A aortic dissection. Although the patient was unable
      to communicate, her family approved an emergency Bentall operation. She regained
      consciousness but developed anisocoria and Glasgow Coma Scale level-4 coma 30
      hours after the operation. Computed tomography showed massive cerebral infarction
      with hernia of the uncus gyri hippocampi. Emergency surgical cerebral
      decompression was performed. The patient survived; after 1 year, she had full
      mental acuity and minor left motor sequelae.

PMID- 18612455
TI  - Spontaneous resolution of coronary artery pseudoaneurysm consequent to
      percutaneous intervention with paclitaxel-eluting stent.
AB  - Pseudoaneurysm formation is a rarely reported phenomenon after percutaneous
      coronary intervention. The natural course and clinical complications of coronary
      pseudoaneurysms are not well described, and the possible contribution of drug
      eluting stents to the formation of coronary artery pseudoaneurysms is ill
      defined. Herein, we describe the case of a patient who experienced pseudoaneurysm
      formation 1 month after deployment of a paclitaxel-eluting stent. Healing was
      delayed, and there was resolution after 2 years of follow-up.

PMID- 18612456
TI  - Acquired pseudoaneurysm of the sinus of Valsalva.
AB  - Localized aneurysms of the sinus of Valsalva are uncommon. Repair is tailored to
      the defective anatomy of the sinus, the aortic valve, and the coronary artery.
      Herein, we report the successful surgical treatment of 2 patients who had
      unruptured pseudoaneurysms of the sinus of Valsalva. An evident fissure in the
      intima of the sinus of Valsalva was seen in both patients. Patient 1 was a 57
      year-old man with annuloaortic ectasia who was diagnosed with pseudoaneurysm of
      the right sinus of Valsalva. A thrombus that had formed in the pseudoaneurysm
      subsequently migrated into the right coronary artery. Aortic root remodeling was
      performed. Patient 2 was a 23-year-old man with a history of blunt chest trauma.
      He developed a pseudoaneurysm in the right sinus of Valsalva and tears on the
      aortic cusps. He underwent aortic valve replacement and repair of the Valsalva
      wall.

PMID- 18612457
TI  - Interrupted aortic arch with transposition of great arteries and hypoplastic
      right ventricle: a successful repair.

PMID- 18612458
TI  - Soldier-specific modification of the mandibular motor neurons in termites.
AB  - Social insects exhibit a variety of caste-specific behavioral tendencies that
      constitute the basis of division of labor within the colony. In termites, the
      soldier caste display distinctive defense behaviors, such as aggressively
      attacking enemies with well-developed mandibles, while the other castes retreat
      into the colony without exhibiting any aggressive response. It is thus likely
      that some form of soldier-specific neuronal modification exists in termites. In
      this study, the authors compared the brain (cerebral ganglion) and the
      suboesophageal ganglion (SOG) of soldiers and pseudergates (workers) in the damp
      wood termite, Hodotermopsis sjostedti. The size of the SOG was significantly
      larger in soldiers than in pseudergates, but no difference in brain size was
      apparent between castes. Furthermore, mandibular nerves were thicker in soldiers
      than in pseudergates. Retrograde staining revealed that the somata sizes of the
      mandibular motor neurons (MdMNs) in soldiers were more than twice as large as
      those of pseudergates. The enlargement of MdMNs was also observed in individuals
      treated with a juvenile hormone analogue (JHA), indicating that MdMNs become
      enlarged in response to juvenile hormone (JH) action during soldier
      differentiation. This enlargement is likely to have two functions: a behavioral
      function in which soldier termites will be able to defend more effectively
      through relatively faster and stronger mandibular movements, and a developmental
      function that associates with the development of soldier-specific mandibular
      muscle morphogenesis in termite head. The soldier-specific enlargement of
      mandibular motor neurons was observed in all examined species in five termite
      families that have different mechanisms of defense, suggesting that such neuronal
      modification was already present in the common ancestor of termites and is
      significant for soldier function.

PMID- 18612459
TI  - Effects of unexpected chords and of performer's expression on brain responses and
      electrodermal activity.
AB  - BACKGROUND: There is lack of neuroscientific studies investigating music
      processing with naturalistic stimuli, and brain responses to real music are,
      thus, largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: This study investigates
      event-related brain potentials (ERPs), skin conductance responses (SCRs) and
      heart rate (HR) elicited by unexpected chords of piano sonatas as they were
      originally arranged by composers, and as they were played by professional
      pianists. From the musical excerpts played by the pianists (with emotional
      expression), we also created versions without variations in tempo and loudness
      (without musical expression) to investigate effects of musical expression on ERPs
      and SCRs. Compared to expected chords, unexpected chords elicited an early right
      anterior negativity (ERAN, reflecting music-syntactic processing) and an N5
      (reflecting processing of meaning information) in the ERPs, as well as clear
      changes in the SCRs (reflecting that unexpected chords also elicited emotional
      responses). The ERAN was not influenced by emotional expression, whereas N5
      potentials elicited by chords in general (regardless of their chord function)
      differed between the expressive and the non-expressive condition.
      CONCLUSIONS/SIGNIFICANCE: These results show that the neural mechanisms of music
      syntactic processing operate independently of the emotional qualities of a
      stimulus, justifying the use of stimuli without emotional expression to
      investigate the cognitive processing of musical structure. Moreover, the data
      indicate that musical expression affects the neural mechanisms underlying the
      processing of musical meaning. Our data are the first to reveal influences of
      musical performance on ERPs and SCRs, and to show physiological responses to
      unexpected chords in naturalistic music.

PMID- 18612460
TI  - Are child and adolescent responses to placebo higher in major depression than in
      anxiety disorders? A systematic review of placebo-controlled trials.
AB  - BACKGROUND: In a previous report, we hypothesized that responses to placebo were
      high in child and adolescent depression because of specific psychopathological
      factors associated with youth major depression. The purpose of this study was to
      compare the placebo response rates in pharmacological trials for major depressive
      disorder (MDD), obsessive compulsive disorder (OCD) and other anxiety disorders
      (AD-non-OCD). METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature
      relevant to the use of psychotropic medication in children and adolescents with
      internalized disorders, restricting our review to double-blind studies including
      a placebo arm. Placebo response rates were pooled and compared according to
      diagnosis (MDD vs. OCD vs. AD-non-OCD), age (adolescent vs. child), and date of
      publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of
      psychotropic medication (mainly non-tricyclic antidepressants) involving youth
      with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other
      anxiety disorders (N = 2533 patients in placebo arms). As hypothesized, the
      placebo response rate was significantly higher in studies on MDD, than in those
      examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs.
      39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002). Children showed a
      higher stable placebo response within all three diagnoses than adolescents,
      though this difference was not significant. Finally, no significant effects were
      found with respect to the year of publication. CONCLUSION: MDD in children and
      adolescents appears to be more responsive to placebo than other internalized
      conditions, which highlights differential psychopathology.

PMID- 18612461
TI  - Differentiation and gene flow among European populations of Leishmania infantum
      MON-1.
AB  - BACKGROUND: Leishmania infantum is the causative agent of visceral and cutaneous
      leishmaniasis in the Mediterranean region, South America, and China. MON-1 L.
      infantum is the predominating zymodeme in all endemic regions, both in humans and
      dogs, the reservoir host. In order to answer important epidemiological questions
      it is essential to discriminate strains of MON-1. METHODOLOGY/PRINCIPAL FINDINGS:
      We have used a set of 14 microsatellite markers to analyse 141 strains of L.
      infantum mainly from Spain, Portugal, and Greece of which 107 strains were typed
      by MLEE as MON-1. The highly variable microsatellites have the potential to
      discriminate MON-1 strains from other L. infantum zymodemes and even within MON-1
      strains. Model- and distance-based analysis detected a considerable amount of
      structure within European L. infantum. Two major monophyletic groups-MON-1 and
      non-MON-1-could be distinguished, with non-MON-1 being more polymorphic. Strains
      of MON-98, 77, and 108 were always part of the MON-1 group. Among MON-1, three
      geographically determined and genetically differentiated populations could be
      identified: (1) Greece; (2) Spain islands-Majorca/Ibiza; (3) mainland
      Portugal/Spain. All four populations showed a predominantly clonal structure;
      however, there are indications of occasional recombination events and gene flow
      even between MON-1 and non-MON-1. Sand fly vectors seem to play an important role
      in sustaining genetic diversity. No correlation was observed between Leishmania
      genotypes, host specificity, and clinical manifestation. In the case of
      relapse/re-infection, only re-infections by a strain with a different MLMT
      profile can be unequivocally identified, since not all strains have individual
      MLMT profiles. CONCLUSION: In the present study for the first time several key
      epidemiological questions could be addressed for the MON-1 zymodeme, because of
      the high discriminatory power of microsatellite markers, thus creating a basis
      for further epidemiological investigations.

PMID- 18612462
TI  - Automated identification of acute hepatitis B using electronic medical record
      data to facilitate public health surveillance.
AB  - BACKGROUND: Automatic identification of notifiable diseases from electronic
      medical records can potentially improve the timeliness and completeness of public
      health surveillance. We describe the development and implementation of an
      algorithm for prospective surveillance of patients with acute hepatitis B using
      electronic medical record data. METHODS: Initial algorithms were created by
      adapting Centers for Disease Control and Prevention diagnostic criteria for acute
      hepatitis B into electronic terms. The algorithms were tested by applying them to
      ambulatory electronic medical record data spanning 1990 to May 2006. A physician
      reviewer classified each case identified as acute or chronic infection.
      Additional criteria were added to algorithms in serial fashion to improve
      accuracy. The best algorithm was validated by applying it to prospective
      electronic medical record data from June 2006 through April 2008. Completeness of
      case capture was assessed by comparison with state health department records.
      FINDINGS: A final algorithm including a positive hepatitis B specific test,
      elevated transaminases and bilirubin, absence of prior positive hepatitis B
      tests, and absence of an ICD9 code for chronic hepatitis B identified 112/113
      patients with acute hepatitis B (sensitivity 97.4%, 95% confidence interval 94
      100%; specificity 93.8%, 95% confidence interval 87-100%). Application of this
      algorithm to prospective electronic medical record data identified 8 cases
      without false positives. These included 4 patients that had not been reported to
      the health department. There were no known cases of acute hepatitis B missed by
      the algorithm. CONCLUSIONS: An algorithm using codified electronic medical record
      data can reliably detect acute hepatitis B. The completeness of public health
      surveillance may be improved by automatically identifying notifiable diseases
      from electronic medical record data.

PMID- 18612463
TI  - Can machines think? Interaction and perspective taking with robots investigated
      via fMRI.
AB  - BACKGROUND: When our PC goes on strike again we tend to curse it as if it were a
      human being. Why and under which circumstances do we attribute human-like
      properties to machines? Although humans increasingly interact directly with
      machines it remains unclear whether humans implicitly attribute intentions to
      them and, if so, whether such interactions resemble human-human interactions on a
      neural level. In social cognitive neuroscience the ability to attribute
      intentions and desires to others is being referred to as having a Theory of Mind
      (ToM). With the present study we investigated whether an increase of human
      likeness of interaction partners modulates the participants' ToM associated
      cortical activity. METHODOLOGY/PRINCIPAL FINDINGS: By means of functional
      magnetic resonance imaging (subjects n = 20) we investigated cortical activity
      modulation during highly interactive human-robot game. Increasing degrees of
      human-likeness for the game partner were introduced by means of a computer
      partner, a functional robot, an anthropomorphic robot and a human partner. The
      classical iterated prisoner's dilemma game was applied as experimental task which
      allowed for an implicit detection of ToM associated cortical activity. During the
      experiment participants always played against a random sequence unknowingly to
      them. Irrespective of the surmised interaction partners' responses participants
      indicated having experienced more fun and competition in the interaction with
      increasing human-like features of their partners. Parametric modulation of the
      functional imaging data revealed a highly significant linear increase of cortical
      activity in the medial frontal cortex as well as in the right temporo-parietal
      junction in correspondence with the increase of human-likeness of the interaction
      partner (computer<functional robot<anthropomorphic robot<human).
      CONCLUSIONS/SIGNIFICANCE: Both regions correlating with the degree of human
      likeness, the medial frontal cortex and the right temporo-parietal junction, have
      been associated with Theory-of-Mind. The results demonstrate that the tendency to
      build a model of another's mind linearly increases with its perceived human
      likeness. Moreover, the present data provides first evidence of a contribution of
      higher human cognitive functions such as ToM in direct interactions with
      artificial robots. Our results shed light on the long-lasting psychological and
      philosophical debate regarding human-machine interaction and the question of what
      makes humans being perceived as human.

PMID- 18612464
TI  - Triacylglycerol fatty acid composition in diet-induced weight loss in subjects
      with abnormal glucose metabolism--the GENOBIN study.
AB  - BACKGROUND: The effect of weight loss on different plasma lipid subclasses at the
      molecular level is unknown. The aim of this study was to examine whether a diet
      induced weight reduction result in changes in the extended plasma lipid profiles
      (lipidome) in subjects with features of metabolic syndrome in a 33-week
      intervention. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples of 9 subjects in the
      weight reduction group and 10 subjects in the control group were analyzed using
      mass spectrometry based lipidomic and fatty acid analyses. Body weight decreased
      in the weight reduction group by 7.8+/-2.9% (p<0.01). Most of the serum
      triacylglycerols and phosphatidylcholines were reduced. The decrease in
      triacylglycerols affected predominantly the saturated short chain fatty acids.
      This decrease of saturated short chain fatty acid containing triacylglycerols
      correlated with the increase of insulin sensitivity. However, levels of several
      longer chain fatty acids, including arachidonic and docosahexanoic acid, were not
      affected by weight loss. Levels of other lipids known to be associated with
      obesity such as sphingolipids and lysophosphatidylcholines were not altered by
      weight reduction. CONCLUSIONS/SIGNIFICANCE: Diet-induced weight loss caused
      significant changes in global lipid profiles in subjects with abnormal glucose
      metabolism. The observed changes may affect insulin sensitivity and glucose
      metabolism in these subjects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00621205.

PMID- 18612465
TI  - Sequence information encoded in DNA that may influence long-range chromatin
      structure correlates with human chromosome functions.
AB  - Little is known about the possible function of the bulk of the human genome. We
      have recently shown that long-range regular oscillation in the motif non-T, A/T,
      G (VWG) existing at ten-nucleotide multiples influences large-scale nucleosome
      array formation. In this work, we have determined the locations of all 100 kb
      regions that are predicted to form distinctive chromatin structures throughout
      each human chromosome (except Y). Using these data, we found that a significantly
      greater fraction of 300 kb sequences lacked annotated transcripts in genomic DNA
      regions > or = 300 kb that contained nearly continuous chromatin organizing
      signals than in control regions. We also found a relationship between the meiotic
      recombination frequency and the presence of strong VWG chromatin organizing
      signals. Large (> or = 300 kb) genomic DNA regions having low average
      recombination frequency are enriched in chromatin organizing signals. As
      additional controls, we show using chromosome 1 that the VWG motif signals are
      not enriched in randomly selected DNA regions having the mean size of the
      recombination coldspots, and that non-VWG motif sets do not generate signals that
      are enriched in recombination coldspots. We also show that tandemly repeated
      alpha satellite DNA contains strong VWG signals for the formation of distinctive
      nucleosome arrays, consistent with the low recombination activity of centromeres.
      Our correlations cannot be explained simply by variations in the GC content. Our
      findings suggest that a specific set of periodic DNA motifs encoded in genomic
      DNA, which provide signals for chromatin organization, influence human chromosome
      function.

PMID- 18612466
TI  - Haptic perception of object curvature in Parkinson's disease.
AB  - BACKGROUND: The haptic perception of the curvature of an object is essential for
      adequate object manipulation and critical for our guidance of actions. This study
      investigated how the ability to perceive the curvature of an object is altered by
      Parkinson's disease (PD). METHODOLOGY/PRINCIPAL FINDINGS: Eight healthy subjects
      and 11 patients with mild to moderate PD had to judge, without vision, the
      curvature of a virtual "box" created by a robotic manipulandum. Their hands were
      either moved passively along a defined curved path or they actively explored the
      curved curvature of a virtual wall. The curvature was either concave or convex
      (bulging to the left or right) and was judged in two locations of the hand
      workspace--a left workspace location, where the curved hand path was associated
      with curved shoulder and elbow joint paths, and a right workspace location in
      which these joint paths were nearly linear. After exploring the curvature of the
      virtual object, subjects had to judge whether the curvature was concave or
      convex. Based on these data, thresholds for curvature sensitivity were
      established. The main findings of the study are: First, 9 out 11 PD patients
      (82%) showed elevated thresholds for detecting convex curvatures in at least one
      test condition. The respective median threshold for the PD group was increased by
      343% when compared to the control group. Second, when distal hand paths became
      less associated with proximal joint paths (right workspace), haptic acuity was
      reduced substantially in both groups. Third, sensitivity to hand trajectory
      curvature was not improved during active exploration in either group.
      CONCLUSION/SIGNIFICANCE: Our data demonstrate that PD is associated with a
      decreased acuity of the haptic sense, which may occur already at an early stage
      of the disease.

PMID- 18612468
TI  - Hepatic haemangopma: enucleate or resect?

PMID- 18612467
TI  - Superfast vocal muscles control song production in songbirds.
AB  - Birdsong is a widely used model for vocal learning and human speech, which
      exhibits high temporal and acoustic diversity. Rapid acoustic modulations are
      thought to arise from the vocal organ, the syrinx, by passive interactions
      between the two independent sound generators or intrinsic nonlinear dynamics of
      sound generating structures. Additionally, direct neuromuscular control could
      produce such rapid and precisely timed acoustic features if syringeal muscles
      exhibit rare superfast muscle contractile kinetics. However, no direct evidence
      exists that avian vocal muscles can produce modulations at such high rates. Here,
      we show that 1) syringeal muscles are active in phase with sound modulations
      during song over 200 Hz, 2) direct stimulation of the muscles in situ produces
      sound modulations at the frequency observed during singing, and that 3) syringeal
      muscles produce mechanical work at the required frequencies and up to 250 Hz in
      vitro. The twitch kinematics of these so-called superfast muscles are the fastest
      measured in any vertebrate muscle. Superfast vocal muscles enable birds to
      directly control the generation of many observed rapid acoustic changes and to
      actuate the millisecond precision of neural activity into precise temporal vocal
      control. Furthermore, birds now join the list of vertebrate classes in which
      superfast muscle kinetics evolved independently for acoustic communication.

PMID- 18612469
TI  - Evaluation of adaptive changes by non-invasive imaging in hepatic vein outflow
      obstruction.
AB  - Hepatic vein outflow obstruction induces remarkable changes of intra-hepatic
      blood circulation; the significance of these changes remains uncertain. Six
      patients with obstruction of the hepatic veins were evaluated by duplex Doppler
      ultrasound and computed tomography. The adaptive changes secondary to obstruction
      were analyzed and their significance was correlated with the clinical findings.
      Four patients presenting unilateral hepatic vein occlusion had unilateral
      reversed portal flow. Two of them, with lobar liver atrophy and contralateral
      compensatory hypertrophy required operation; the other two, with normal
      appearance of the liver, benefitted from conservative treatment. Two patients
      with bilateral hepatic vein occlusion, intra-hepatic bypasses, bilateral lobar
      atrophy and caudate lobe hypertrophy, received operations. Intrahepatic
      unilateral portal flow reversal compensates for unilateral hepatic outflow
      obstruction. The combination of complete or subtotal hepatic vein obstruction and
      atrophy-hypertrophy complex predicates advanced disease despite flow reversal or
      spontaneous shunt.

PMID- 18612470
TI  - Review article: Spectrum of biliary infections in the West and in the East.
AB  - Biliary infections are an important cause of morbidity in the Western world. With
      regard to epidemiology, etiology, microbiological spectrum, prevalence, location
      and composition of gallstones, pathogenesis, clinical sign and therapy, there are
      large differences between the spectrum of biliary infections in the East and in
      the West (Table 1). In Western countries, gallstones are found in 10 to 40%. In
      Eastern countries, the incidence of gallstones is only 2 to 6%. Some eighty-five
      percent of the gallstones in the West are cholesterol stones, in contrast to the
      East, where 97% are bile pigment stones. The most important difference is
      characterized by the origin of common bile duct stones. In the West, common bile
      duct stones generally originate in the gallbladder, in contrast to the East,
      where primary common bile duct stones are often found--especially in the
      intrahepatic segments--with no evidence of gallbladder stones. The sex
      distribution male to female in the West is 1:2, in the East 1:1. In the West,
      biliary infections occur mainly in an elderly population, 50% being older than 70
      years. In the East, biliary infections appear also in younger people, 50% being
      younger than 40 years. Parasites play an aetiological role in the East, but not
      in the West. The typical therapy of gallstones in the West is cholecystectomy,
      and of common bile duct stones endoscopic sphincterotomy. Due to the frequency of
      intrahepatic stones in Eastern Countries, the therapeutic spectrum there includes
      even large hepatic resections and biliary enteric anastomoses.

PMID- 18612471
TI  - The role of leucocyte-derived free oxygen radicals in the pathogenesis of
      experimental acute pancreatitis.
AB  - The role of free oxygen radicals in experimental acute pancreatitis induced by
      common bile duct ligation was investigated by measuring malondialdehyde levels in
      the rat pancreas. Also, the potential role of leucocytes as the source of free
      oxygen radicals was tested by inducing leukopenia with methotrexate. The
      malondialdehyde levels in the control, pancreatitis and pancreatitis +
      methotrexate groups were 9.6 +/- 2.0, 44.8 +/- 11.4, and 25.6 +/- 5.0 nmol
      malondialdehyde/ g pancreas tissue respectively. The corresponding
      histopathological severity scores were 0.5 +/- 0.7, 8.1 +/- 1.2 and 3.7 +/- 1.1.
      The results suggest that the leucocyte may be an important source of free oxygen
      radicals in this experimental model.

PMID- 18612472
TI  - Comment by R. Adam and H. Bismuth.

PMID- 18612473
TI  - Biochemical prediction of acute cholangitis and symptomatic bile duct stones by
      gallstone hepatitis.
AB  - We have adopted the clinical concept of gallstone hepatitis indicated by marked
      serum transaminase elevation due to an acute inflammatory liver cell necrosis in
      the early stages of gallstone impaction in the bile duct as clinical and
      biochemical criteria for identifying high-risk patients for acute cholangitis or
      bile duct stones causing symptoms (symptomatic bile duct stones, SBDS). One
      hundred and fifty-eight (80.2%) of 197 patients with acute gallstone disease and
      concomitant elevation of serum transaminase (gallstone hepatitis) underwent
      emergency treatment, either surgery (138 patients) or percutaneous transhepatic
      biliary drainage (PTBD)/endoscopic sphincterotomy (ES) (20 patients). One hundred
      and forty-two (89.9%) and 67 (42.4%) were confirmed to have SBDS and acute
      cholangitis, respectively, in the early stage of the disease. The majority of the
      patients who had no bile duct stones identified at surgery had either biliary
      pancreatitis or multiple small stones in the gallbladder. They were assumed to
      have migrating stones or false negative operative cholangiograms. In conclusion,
      gallstone hepatitis indicates that SBDS and acute cholangitis are probable, and
      facilitates rapid selection of patients for urgent biliary tract exploration in
      patients with acute gallstone disease.

PMID- 18612475
TI  - A novel method of determining portal systemic shunting using biodegradable 99Tcm
      labelled albumin microspheres.
AB  - Portal systemic shunting (PSS) and portal pressure were measured in control rats
      and in animals with portal hypertension induced by partial portal vein ligation
      (PPVL). The portal pressure in rats with partial portal vein ligation (13.4 +/-
      0.5 mm.Hg.) was significantly higher (p < 0.005) than in the control group (9.6
      +/- 0.6 mm.Hg.). Portal systemic shunting measured by consecutive injections of
      radiolabelled methylene diphosphonate (MDP), a non-diffusable marker and albumin
      microspheres directly into the splenic pulp was significantly increased (P <
      0.005) in the portal hypertensive animals (30.8 +/- 2.5%) compared to sham
      operated rats (2.6 +/- 1.5%). Similarly, in portal hypertensive rats portal
      systemic shunting measured by intrasplenic injections of radiolabelled cobalt
      microspheres (37.1 +/- 3.9%) was significantly greater (p < 0.005) than in
      control animals. There was a good correlation and agreement (r = 00.97) between
      the two methods of measuring portal systemic shunting. However because the
      (99)Tc(m)-albumin microspheres are biodegradable the method allows portal
      systemic shunting to be measured in man. Furthermore since the computer adjusts
      the baseline to zero after each determination of portal systemic shunting the
      methodology allows repeated measurements to be made.

PMID- 18612476
TI  - Duodenal malignant somatostatinoma.
AB  - The authors report a case of hormonally silent duodenal somatostatinoma. The main
      clinical features, the natural history and the currently available therapies of
      these rare neoplasms are described on the basis of this case and of the
      scientific literature. Although the antiblastic therapies are still debated, the
      patient showed a surprising outcome following chemotherapy.

PMID- 18612477
TI  - Papillary adenocarcinoma of the common bile duct.
AB  - Five patients with papillary adenocarcinoma of the common bile duct (CBD) are
      described. These are rare tumors and make up 5% of all malignant tumors of the
      biliary tract. The symptoms and signs at the time of initial diagnosis resemble
      benign obstructive lesions of the bile ducts. The tumor is soft, less invasive to
      adjacent tissues and tends to grow into the lumen. The early onset of the
      symptoms results in early intervention, with a better prognosis. Two of our
      patients are doing well after two and four years, where as three others were
      readmitted with recurrent disease.

PMID- 18612478
TI  - Combined interventional radiological and endoscopical approach for the treatment
      of a postoperative biliary stricture and fistula.
AB  - A 43-year old woman was admitted 11 days after open cholecystectomy with a
      iatrogenic bile duct injury. On admission the patient showed an uncontrolled
      biliary fistula through an external drain placed at an emergency laparotomy for
      biliary peritonitis with fever and jaundice. PTC showed a biliary stricture type
      II (Bismuth). A percutaneous drainage was performed to decompress the biliary
      system. Three weeks later, percutaneous balloon dilatation of the stricture was
      performed. However, bile leakage persisted. In a combined transhepatic/
      endoscopic procedure, the percutaneous biliary drainage was replaced by a
      nasobiliary tube. One week later, no stricture was found and the biliary leak was
      sealed. The patient could be discharged without symptoms or signs of cholestasis.
      The multidisciplinary management of post-operative biliary fistula is presented,
      comparing the role of interventional radiology, endoscopy and surgery.

PMID- 18612479
TI  - Improvement of rat survival and liver mitochondrial function in biliary
      obstruction after treatment with sodium thiosulfate.
AB  - The exact cause of liver failure occurring after long standing biliary
      obstruction is not known. Impairment of hepatic mitochondrial respiration was
      postulated in some studies. Sodium thiosulphate (STS) is known to have a
      protective effect on liver function during administration of hepatotoxic
      chemotherapy. In the present experimental study the effect of treatment with STS
      in the presence of obstructive jaundice was studied by determination of the
      survival rate of rats subjected to biliary obstruction and by polarographic
      determination of the hepatic mitochondrial function. Treatment with STS was found
      to result in a significant improvement in rats' survival rate (p < 0.05).
      Polarography demonstrated significant preservation of mitochondrial respiratory
      capacity after treatment with STS. The results of the present study show that the
      deterioration in liver function in the presence of biliary obstruction is
      probably caused by impairment of mitochondrial respiration. This may be preserved
      by treatment with STS. The exact explanation of its effect is not yet clear.

PMID- 18612484
TI  - Outcomes and risk factors in 1,609 carotid endarterectomies.
AB  - Severe carotid stenosis is typically treated with carotid endarterectomy (CEA),
      but there is debate about the safety of this procedure in patients with occlusion
      of the contralateral artery, previous CEA in the same artery, and other risk
      factors. To evaluate the association of these factors with outcomes in standard
      CEA with Dacron patch angioplasty, we examined the records of 1,609 consecutive
      isolated CEAs performed at our institution over a 10-year period on 1,400
      patients (851 men and 549 women; mean age, 69.5 yr) with symptomatic or high
      grade asymptomatic carotid lesions. Twenty-three patients (1.4%) had
      perioperative strokes, of which 2 were fatal. The overall same-admission
      mortality was 0.2% (4 patients). Same-admission stroke/death was more likely in
      patients with any history of tobacco use (odds ratio [OR], 4.6; 95% confidence
      interval [CI], 1.6-13.6), contralat-eral occlusion (OR, 3.3; 95% CI, 1.2-9.1),
      angina with a Canadian Cardiovascular Society classification of 2 or greater (OR,
      3.2; 95% CI, 1.4-7.6), or transient ischemic attack within the 6 weeks before
      surgery (OR, 2.4; 95% CI, 1.05-5.3). A total of 9 patients (0.6%) died within 30
      days of CEA; our multivariate analysis did not reveal any significant predictors
      of 30-day mortality. We conclude that standard CEA with patch angioplasty is
      associated with low rates of death and morbidity for most patients, but patients
      with any history of tobacco use, substantial angina, contralateral occlusion, or
      preoperative transient ischemic attack may have an elevated risk of adverse
      outcomes.

PMID- 18612485
TI  - Ventricular septal defect closure in a patient with VACTERL syndrome:
      anticipating sequelae in a rare genetic disorder.
AB  - Noncardiac components of genetic disorders can complicate the operative and
      postoperative courses of pediatric cardiac surgery patients. Prolonged hospital
      stay, increased treatment cost, morbidity, and death are more likely in this
      subgroup of patients. Ventricular septal defect, which is a component of various
      genetic disorders, has a 22.3% incidence in VACTERL syndrome--a rare, nonrandom
      pattern of birth defects. Herein, we discuss the impact of ventricular septal
      defect closure in a 4-month-old girl who was diagnosed after birth with VACTERL
      syndrome.

PMID- 18612486
TI  - Cavernous hemangioma atypically located at the left brachial region.

PMID- 18612487
TI  - Giant aneurysm 25 years after patch aortoplasty for aortic coarctation.

PMID- 18612488
TI  - Early outcomes of double-vessel coronary endarterectomy in comparison with single
      vessel coronary endarterectomy.
AB  - Our goal was to investigate the safety of single- and double-vessel coronary
      endarterectomy as an adjunct to coronary artery bypass grafting in patients with
      diffuse coronary disease. In reviewing the records of 9,443 patients who
      underwent isolated coronary artery revascularization over a 4-year period, we
      found 310 patients (3.28%) who underwent concomitant coronary artery
      endarterectomy, 39 of whom (12.6%) required double endarterectomy (Group 2) and
      the rest of whom required single endarterectomy (Group 1). Variables of these
      groups were compared by means of univariate analysis. In Group 1, 76.3% were men,
      with a mean age of 58.73 +/- 9.36 yr. Regarding postoperative myocardial
      infarction as evaluated by electrocardiography and the MB isoenzyme of creatine
      kinase, 13% of the patients in Group 1 and 15.4% in Group 2 were so affected. The
      early mortality rate was 3.3% in Group 1 and 10.3% in Group 2 (P <0.05). In
      univariate analysis, the following variables were significant: 3-vessel disease,
      postoperative atrial fibrillation, dialysis, length of hospital stay, and death.
      In multivariate analysis of endarterectomized arteries, the vascular combinations
      most strongly associated with death were left anterior descending coronary artery
      + right coronary artery and right coronary artery + diagonal. There was no
      association between endarterectomy of particular vessels and perioperative
      myocardial infarction. Although coronary endarterectomy has become a safe
      procedure, adding a 2nd endarterectomy worsens the prognosis dramatically, and
      surgeons should be especially cautious about such an addition if the 1st
      endarterectomy is in left anterior descending coronary artery or right coronary
      artery territory.

PMID- 18612489
TI  - Dilated cardiomyopathy and myocardial infarction secondary to congenital
      generalized lipodystrophy.
AB  - Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome,
      is a very rare hereditary syndrome that is characterized by an almost complete
      absence of adipose tissue from birth. Cardiac involvement seems to have
      substantial influence in the long-term prognosis. Herein, we report an apparently
      unique case of congenital generalized lipodystrophy with cardiac sequelae. A 17
      year-old woman, diagnosed in childhood with Berardinelli-Seip syndrome, presented
      with severe epigastric pain that was secondary to previous myocardial infarction.
      The patient had ischemia, dilated cardiomyopathy, and congestive heart failure,
      but no coronary artery disease. She was discharged from the hospital in stable
      condition after 3 days of medical treatment. To our knowledge, this is the 1st
      reported case of congenital generalized lipodystrophy with dilated
      cardiomyopathy, congestive heart failure, severe mitral regurgitation, and
      inferior myocardial infarction as cardiac sequelae of this syndrome--but without
      evidence of coronary artery disease or cardiac hypertrophy. In addition to
      discussing this patient's case, we present diagnostic and therapeutic approaches
      to Berardinelli-Seip syndrome.

PMID- 18612490
TI  - Einthoven's string galvanometer: the first electrocardiograph.
AB  - Willem Einthoven (1860--1927), known as the creator of the electrocardiograph,
      won a Nobel Prize in 1924 for his contributions to the field of
      electrocardiography. He was dedicated to research and learning. In developing the
      electrocardiograph, Einthoven built on the work of earlier physiologists who had
      studied the electrical mechanisms of the heart. Each earlier invention proved
      important by contributing concepts and knowledge that would shape Einthoven's
      device. Herein, we review the history of the electrocardiograph, with a focus on
      Willem Einthoven's quest to make the device a practical clinical instrument in
      the diagnosis of cardiac abnormalities.

PMID- 18612491
TI  - Left atrial size may predict exercise capacity and cardiovascular events in
      patients with heart failure.
AB  - Our aim was to investigate, in patients with heart failure, the relationship
      between left atrial size and exercise capacity and cardiovascular events. Seventy
      five patients (67 men and 8 women; mean age, 53.4 +/- 8.8 yr) with left
      ventricular ejection fractions of < or =0.45 (New York Heart Association
      functional classes I-III) were matched by age and sex with 20 healthy control
      subjects. Echocardiographic examinations were performed, as was exercise testing
      by the modified Bruce protocol. Patients were monitored for a period of 330 to
      480 days for cardiac death or for heart failure that required hospitalization.
      The indexed left atrial diastolic size (beta level = -0.534, P <0.001) and left
      ventricular late diastolic filling velocity (beta level = 0.247, P <0.017) were
      the most important values in predicting low exercise capacity. The only
      independent predictor of low exercise capacity (<5 METS) was the indexed left
      atrial diastolic size (odds ratio, 1.428; 95% confidence interval, 1.09-1.702; P
      <0.001). Every 1 mm/m2 increase in indexed left atrial diastolic dimension caused
      a 42.8% increase in the risk of severe heart failure (exercise capacity, <5
      METS). Independent predictors for cardiovascular events were indexed as left
      atrial systolic size (odds ratio, 1.383; 95% confidence interval, 1.145-1.671; P
      <0.001) and left ventricular early diastolic/late diastolic filling velocity
      (odds ratio, 1.096; 95% confidence interval, 1.010-1.189; P <0.027). Indexed left
      atrial diastolic and left atrial systolic size predict exercise capacity and
      cardiovascular events, respectively, in New York Heart Association functional
      class I through III heart failure patients.

PMID- 18612492
TI  - Iatrogenic circumflex coronary lesion in mitral valve surgery: case report and
      review of the literature.
AB  - Ischemic iatrogenic lesions can complicate surgical procedures on the mitral
      valve. One of the causative mechanisms is direct injury to or distortion of the
      circumflex coronary artery. The risk of damaging the circumflex coronary artery
      depends mainly upon the proximity of that vessel to the posterior segment of the
      mitral annulus, and this varies from patient to patient. Herein, we report a case
      of iatrogenic circumflex coronary artery lesion after mitral annuloplasty, and we
      review the literature on the subject, in order to highlight a possible
      relationship between iatrogenic circumflex lesions and coronary dominance. In a
      60-year-old man who had severe mitral regurgitation due to prolapse of both
      leaflets, preoperative coronary angiography showed irregularities only along the
      left anterior descending coronary artery and a coronary network of right
      dominance. The patient underwent mitral annuloplasty (32-mm Carpentier-Edwards
      ring) by means of minimally invasive right thoracotomy through the right 4th
      intercostal space (HeartPort). When the procedure was over, and before the
      patient was taken to intensive care, ventricular fibrillation developed; the
      administration of direct-current shock (200 joules) resulted in a resumption of
      sinus rhythm. Repeat transesophageal echocardiography showed posterolateral
      dyskinesis of the left ventricle and ST-segment elevation suggestive of acute
      lateral myocardial infarction. Emergency cardiac catheterization revealed a
      subocclusion of the distal circumflex coronary artery. Dual percutaneous
      angioplasty and stenting (Taxus, 2.5 x 24 mm) was performed with optimal result.
      At the 1-year follow-up, the patient showed good results of the mitral
      annuloplasty.

PMID- 18612493
TI  - CentriMag left ventricular assist system: cannulation through a right
      minithoracotomy.
AB  - The CentriMag left ventricular assist system can be used for perioperative or
      postcardiotomy circulatory support of the failing heart. The device resides at
      the patient's bedside, and the cannulae are usually inserted through a midline
      sternotomy, with the inflow cannula in the left ventricle or right superior
      pulmonary vein and the outflow cannula in the aorta. In a patient whose chest has
      been closed and who has a delayed need for temporary mechanical support, a less
      invasive method of left ventricular assist device cannula insertion is preferred.
      In these cases, the CentriMag cannulae can be inserted through a right
      minithoracotomy with the inflow cannula in the right superior pulmonary vein and
      the outflow cannula in the aorta, with no heparinization. Herein, we describe
      this approach in a patient who experienced postcardiotomy cardiogenic shock after
      aortocoronary bypass surgery. This technique may facilitate ambulation and
      recovery in selected patients.

PMID- 18612494
TI  - Circumflex coronary artery bypass via the posterior interatrial sulcus and under
      the venae cavae.
AB  - During coronary artery bypass grafting, the length of the graft to the circumflex
      coronary artery or its end branches can be underestimated because of the
      posterior location of the circumflex. Herein, we describe a new bypass route-
      which we consider the shortest--to the ascending aorta. In 2 patients, during
      proximal anastomosis of the saphenous vein bypass graft (via a route either
      anterior to the pulmonary artery or the transverse sinus) from the circumflex to
      the ascending aorta, the vein graft (approximately 5-6 cm in length) proved too
      short. We performed bypass in a new direction--from the circumflex coronary
      artery to the right side of the ascending aorta, under the inferior and superior
      venae cavae and along the interatrial groove--without the need for graft
      lengthening. To our knowledge, the bypass route to the circumflex system
      described herein is new. This new route can be successfully used when the bypass
      conduit is too short to follow the conventional route. Our 2 patients benefited
      from this approach and were in Canadian Cardiovascular Society Class l two years
      after the surgical procedure.

PMID- 18612495
TI  - Circumferential intimal flap prolapsing into the left ventricle.

PMID- 18612496
TI  - Anastomotic leak after cabrol composite graft procedure: diagnosis by computed
      tomographic angiography and treatment by covered stent.

PMID- 18612497
TI  - Caseous calcification of the mitral annulus.

PMID- 18612499
TI  - Angiographic documentation of aortoiliac occlusion in Leriche's syndrome.

PMID- 18612498
TI  - Enhancing hypertension awareness and management in the elderly: lessons learned
      from the Airdrie Community Hypertension Awareness and Management Program (A
      CHAMP).
AB  - BACKGROUND: High blood pressure (BP) is an established and modifiable
      cardiovascular risk factor; however, awareness and management of this primarily
      asymptomatic disease remains suboptimal. OBJECTIVES: The Airdrie Community
      Hypertension Awareness and Management Program (A-CHAMP) was a community-based BP
      program for seniors designed to improve public and health care provider awareness
      and management of hypertension. METHODS: Volunteer peer health educators (VPHEs)
      were recruited from the community and trained to manage BP screening sessions in
      local pharmacies. Airdrie (Alberta) residents 65 years of age and older were
      invited by their family physicians (FPs) to attend the A-CHAMP sessions. VPHEs
      identified participants' cardiovascular risk factors, assessed BP with a
      validated automated device and implemented a management algorithm. Participants
      with BP higher than 159/99 mmHg were directed to their pharmacists and FPs. All
      participants with elevated BP at the initial A-CHAMP session were invited to
      return to a follow-up session four to six months later. RESULTS: Thirty VPHEs
      were recruited and trained. All 15 FPs and all six pharmacies in Airdrie
      participated. VPHEs assessed 406 seniors (approximately 40% of Airdrie seniors)
      during the three-month program. One hundred forty-eight participants (36.5%) had
      elevated BP at their first session. Of these, 71% returned for the follow-up
      session four to six months later. The mean (+/- SD) systolic BP decreased by
      16.9+/-17.2 mmHg (P<0.05, n=105) compared with their first visit, and 56% of
      participants (59 of 105) reached Canadian targets for BP. CONCLUSIONS: A-CHAMP
      raised awareness, and identified and managed seniors with hypertension. At follow
      up, BP showed statistically and clinically significant and sustained improvement.
      Participating health care providers and VPHEs indicated that A-CHAMP was
      effective and feasible in improving awareness and control of hypertension.

PMID- 18612500
TI  - Intravenous immunoglobulin treatment for acute fulminant inflammatory
      cardiomyopathy: series of six patients and review of literature.
AB  - BACKGROUND: Although an autoimmune mechanism has been postulated for myocarditis
      and acute-onset inflammatory dilated cardiomyopathy (DCM), immunomodulatory
      treatment strategies are still under investigation. METHODS AND RESULTS: The
      clinical data of six patients with acute inflammatory DCM referred for evaluation
      for possible heart transplantation were reviewed. All patients were admitted with
      acute congestive heart failure and severely impaired left ventricular (LV)
      function and were treated with high-dose (2 g/kg) intravenous immunoglobulin
      (IVIG). The diagnosis of acute inflammatory DCM was based on recent onset of
      congestive heart failure (New York Heart Association functional class III or IV)
      with severely depressed LV ejection fraction ([LVEF] 30% or lower) occurring
      shortly after viral-like illness. All patients had inflammation on endomyocardial
      biopsy or elevated cardiac enzymes, as well as a normal coronary angiogram. All
      patients were in New York Heart Association class I or II at the time of hospital
      discharge. The mean LVEF improved from 21.7+/-7.5% at baseline to 50.3+/-8.6% at
      discharge (P=0.005). Four patients had complete recovery (LVEF 50% or higher) and
      two patients had partial LV recovery. Patients were followed for a median 13.2
      months (range two to 24 months) and had a mean LVEF of 53+/-6% (P not significant
      versus LVEF at discharge). CONCLUSIONS: Therapy with intravenous high-dose IVIG
      may be a potentially useful treatment in selected patients if given early in the
      course of acute fulminant inflammatory DCM. A randomized, prospective trial is
      warranted to prove the real benefit of IVIG in this patient population.

PMID- 18612501
TI  - Prevalence of cardiometabolic risk factors by weight status in a population-based
      sample of Quebec children and adolescents.
AB  - BACKGROUND: There are few data on the prevalence of cardiometabolic risk factors
      in population-based samples of overweight and obese youth. OBJECTIVES: To compare
      the prevalence of individual and multiple cardiometabolic risk factors across
      body mass index (BMI) categories in a population-based sample of youth. METHODS:
      In 1999, a school-based survey of a provincially representative sample of youth
      nine, 13 and 16 years of age was conducted in Quebec (1778 boys, 1835 girls).
      Overweight was defined as BMI in the 85th percentile or higher and lower than the
      95th percentile of the Centers for Disease Control and Prevention 2000 growth
      charts, and obesity was defined as BMI in the 95th percentile or higher. Levels
      of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, high
      density lipoprotein cholesterol, triglycerides, insulin, glucose, C-reactive
      protein and systolic blood pressure were categorized as desirable, borderline or
      unfavourable. RESULTS: The proportions of overweight and obese participants were
      14% and 10% in boys, and 14% and 7% in girls, respectively. With the exception of
      total cholesterol and low-density lipoprotein cholesterol in girls, and glucose
      in both sexes, the prevalence of all investigated risk factors (borderline or
      unfavourable) was significantly higher among overweight and obese participants.
      Almost one-third of obese participants had unfavourable levels of at least two of
      seven risk factors (apolipoprotein B, high-density lipoprotein cholesterol,
      triglycerides, insulin, glucose, C-reactive protein and systolic blood pressure)
      compared with 3% of normal weight participants (adjusted OR 15 and 18 in boys and
      girls, respectively). Thirty-four per cent of obese youth did not have
      unfavourable levels of any risk factor. CONCLUSION: There is marked heterogeneity
      in the association between excess weight and cardiometabolic risk factors.
      Nonetheless, the present study highlights a high prevalence of multiple risk
      factors in a population-based sample of overweight and obese youth.

PMID- 18612503
TI  - Technical failure to perform cardiac resynchronization therapy: use of cardiac
      magnetic resonance imaging techniques to clarify a left-sided superior vena cava
      and coronary sinus morphology.
AB  - The most common reason for failure to implant a left ventricular lead to deliver
      cardiac resynchronization therapy is the presence of unfavourable coronary venous
      anatomy. The present report illustrates the use of cardiac magnetic resonance
      imaging to delineate the anatomy of a left-sided superior vena cava in two
      patients in whom permanent cardiac pacing was unattainable.

PMID- 18612502
TI  - Long-term prognosis of south Asians following acute coronary syndromes.
AB  - BACKGROUND: South Asians (SAs) have a higher prevalence of coronary artery
      disease than Caucasians. The long-term prognosis following acute coronary
      syndromes (ACS) in SA compared with non-SA patients is unclear. OBJECTIVES: To
      compare the long-term adverse cardiovascular outcomes between SA and non-SA
      patients who have ACS. METHODS: A case-control study of 65 consecutive SA
      patients admitted with ACS to the McGill University Health Centre (Montreal,
      Quebec) between 1995 and 2000 was conducted. Control subjects included 65 non-SA
      patients admitted to the same hospital with ACS matched by age, sex and year of
      hospitalization. RESULTS: The mean +/- SD age was 59.7+/-9.9 years and 12% of
      patients were women. There were more cases of diabetes mellitus among the SA
      patients than non-SA patients (43% versus 23%, respectively). Only 19% of SA
      patients were active smokers, compared with 34% of non-SA patients. At one year,
      35% of SA patients had undergone coronary artery bypass graft surgery, compared
      with 22% of non-SA patients. One-year mortality was increased among the SA
      patients compared with the non-SA patients (6% versus 2%, respectively). However,
      SA ethnicity was not an independent predictor of one-year adverse cardiovascular
      outcomes. CONCLUSIONS: The present study demonstrated an increased prevalence of
      diabetes mellitus among the SA patients with ACS compared with non-SA patients.
      SA patients had increased one-year mortality compared with non-SA patients.
      However, SA ethnicity was not an independent predictor of one-year mortality and
      coronary intervention.

PMID- 18612504
TI  - Complete occlusion of the proximal subclavian artery post-CABG: presentation and
      treatment.
AB  - Atherosclerotic disease of the proximal left subclavian artery is an uncommon
      cause of angina in the post-coronary artery bypass graft patient, and is termed
      coronary-subclavian steal syndrome. Typical manifestations include cardiac
      symptoms of angina and noncardiac symptoms of lightheadedness, left arm numbness
      or weakness, and a difference in blood pressure of more than 20 mmHg between both
      arms. A case of complete proximal occlusion of the subclavian artery is reported.
      The clinical picture, investigations and treatment are described. Historical
      treatments of occlusive disease include surgical bypass graft and, more recently,
      percutaneous transluminal angioplasty. The patient underwent percutaneous
      transluminal angioplasty with stenting by a retrograde approach, with an
      excellent short-term response, but ultimately required a carotid subclavian
      bypass due to restenosis.

PMID- 18612505
TI  - Corrected QT interval prolongation after an overdose of escitalopram, morphine,
      oxycodone, zopiclone and benzodiazepines.
AB  - Escitalopram is the recently marketed S-enantiomer of the widely used
      antidepressant citalopram. Data from intentional overexposure to this medication
      are limited. Twelve-lead electrocardiogram (ECG) effects from racemic citalopram
      have been described; however, the present report is the first, to the best of the
      authors' knowledge, that describes all the reported abnormalities in a single
      patient receiving escitalopram. A 52-year-old man with a history of depression
      treated with escitalopram 10 mg/day, extended-release morphine 30 mg/day and
      zopiclone 15 mg/day was found unconscious at his home. He was known to have
      attempted suicide three weeks previously. Partially emptied bottles of
      escitalopram, morphine, oxycodone, zopiclone, lorazepam and diazepam were found
      close to the patient. He was transferred to the emergency department, where
      airway management and other supportive care were initiated. The patient was
      transferred to the intensive care unit. The initial 12-lead ECG demonstrated
      junctional rhythm at 48 beats/min, a wide complex escape (145 ms) with right
      bundle branch morphology and a prolonged corrected QT interval at 650 ms. Cardiac
      monitoring was undertaken. No ventricular arrhythmias or torsade de pointes were
      detected. No specific treatment for shortening the QT was implemented. Another 12
      lead ECG performed 48 h later demonstrated sinus tachycardia with a normal
      corrected QT, normal PR interval and normal QRS duration. The effects of the
      overdose of escitalopram on the ECG and its interactions with other drugs are
      reviewed.

PMID- 18612506
TI  - A young woman with dyspnea.
AB  - A 35-year-old Sri Lankan woman (gravida 3, para 3, abortus 0) presented to the
      Jewish General Hospital (Montreal, Quebec) with shortness of breath and diffuse
      swelling. She was five months postpartum of her most recent delivery, which was
      complicated by pre-eclampsia and gestational diabetes. She described a three-week
      history of progressive exertional dyspnea, orthopnea and paroxysmal nocturnal
      dyspnea. There was no history of recent viral illness, and the patient had no
      traditional risk factors for coronary artery disease. A physical examination,
      laboratory results and echocardiography were typical for heart failure. A
      presumptive diagnosis of peripartum cardiomyopathy was made. To initiate a
      transplant referral, coronary angiography was performed. Six discrete
      atherosclerotic lesions were found, notably left main equivalent disease. A
      diagnosis of ischemic cardiomyopathy was made, and the patient was referred for
      high-risk coronary artery bypass surgery and transplant. The present case
      illustrates the excess burden of coronary artery disease borne in south Asian
      patient populations.

PMID- 18612507
TI  - Is this pacemaker working properly? Prolongation of the atrial escape interval
      following activation of the ventricular safety pacing algorithm in a dual-chamber
      implantable cardioverter defibrillator with atrial-based, lower rate timing.
AB  - With the introduction of various new pacing features and algorithms, 12-lead
      electrocardiogram analysis of paced rhythms can be a challenging undertaking. An
      incorrect interpretation may lead to an inappropriate medical decision in the
      care of such patients. The authors present an interesting paced 12-lead
      electrocardiogram that posed a diagnostic challenge.

PMID- 18612508
TI  - Angiographic time course of in-stent restenosis with zotarolimus drug-eluting
      stents.

PMID- 18612509
TI  - Asymptomatic extensive coronary cameral fistulae involving the left ventricle.

PMID- 18612510
TI  - Cold controlled chemistry.
AB  - Collisions of molecules in a thermal gas are difficult to control. Thermal motion
      randomizes molecular encounters and diminishes the effects of external radiation
      or static electromagnetic fields on intermolecular interactions. The effects of
      the thermal motion can be reduced by cooling molecular gases to low temperatures.
      At temperatures near or below 1 K, the collision energy of molecules becomes less
      significant than perturbations due to external fields. At the same time,
      inelastic scattering and chemical reactions may be very efficient in low
      temperature molecular gases. The purpose of this article is to demonstrate that
      collisions of molecules at temperatures below 1 K can be manipulated by external
      electromagnetic fields and to discuss possible applications of cold controlled
      chemistry. The discussion focuses on molecular interactions at cold (0.001-2 K)
      and ultracold (<0.001 K) temperatures and is based on both recent theoretical and
      experimental work. The article concludes with a summary of current challenges for
      theory and experiment in the research of cold molecules and cold chemistry.

PMID- 18612511
TI  - Mechanical properties of composite polymer microstructures fabricated by
      interference lithography.
AB  - We demonstrate that organized, porous, polymer microstructures with continuous
      open nanoscale pores and a sub-micron spacing obtained via interference
      lithography can be successfully utilized in a non-traditional field of ordered
      polymer microcomposites. The examples presented here include porous matrices for
      the fabrication of binary, glassy-rubbery microcomposites with intriguing
      mechanical properties with large energy dissipation and lattice-controlled
      fracturing.

PMID- 18612512
TI  - [Cyanil](2)(2-) dimers possess long, two-electron ten-center (2e(-)/10c)
      multicenter bonding.
AB  - A long, two-electron ten-center (2e(-)/10c) [8 carbon plus 2 oxygen] bond in
      diamagnetic dimers of radical-anion tetracyano-1,4-benzoquinoneide (cyanil, [Q] (
      )), [Q](2)(2-), is described by B3LYP and CASSCF(2,2)/MCQDPT calculations.

PMID- 18612513
TI  - Glucose, sucrose and trehalose are partially excluded from the interface of
      hydrated DMPC bilayers.
AB  - The free energy of membrane-sugar interactions for DMPC bilayers hydrated in
      binary aqueous mixtures of, respectively, glucose, sucrose and trehalose was
      directly determined by differential vapor pressure measurements using both
      isothermal and temperature scanning modes. It was consistently found that the
      membrane interacts more favorably with water than with the sugars, and thus
      concluded that the sugars are preferentially excluded from the hydration layers.
      This observation contradicts a number of recent computational studies.

PMID- 18612514
TI  - Hydrogen bonding to divalent sulfur.
AB  - A combination of vapor phase infrared spectroscopy and ab initio calculations has
      been used to show that sulfur is weaker than, but nearly equivalent to, oxygen as
      a hydrogen bond acceptor. Enthalpies of hydrogen bond formation were obtained for
      the hydrogen bonded complexes formed between methanol and either dimethyl sulfide
      or dimethyl ether by temperature dependence studies of the infrared spectra.

PMID- 18612515
TI  - Benchmarking the performance of spin-component scaled CC2 in ground and
      electronically excited states.
AB  - A generalization of the spin-component scaling and scaled opposite-spin
      modifications of second-order Moller-Plesset perturbation theory to the
      approximate coupled-cluster singles-and-doubles model CC2 (termed SCS-CC2 and SOS
      CC2) is discussed and a preliminary implementation of ground and excited state
      energies and analytic gradients is reported. The computational results for bond
      distances, harmonic frequencies, adiabatic and 0-0 excitation energies are
      compared with experimental results to benchmark their performance. It is found
      that both variants of the spin-scaling increase the robustness of CC2 against
      strong correlation effects and lead for this method even to somewhat larger
      improvements than those observed for second-order Moller-Plesset perturbation
      theory. The spin-component scaling also enhances systematically the accuracy of
      CC2 for 0-0 excitation energies for pi --> pi* and n --> pi* transitions, if
      geometries are determined at the same level.

PMID- 18612516
TI  - Analytic three-dimensional 'MLR' potential energy surface for CO(2)-He, and its
      predicted microwave and infrared spectra.
AB  - A three-dimensional, analytic potential energy surface for CO(2)-He that
      explicitly incorporates its dependence on the Q(3) asymmetric-stretch normal-mode
      coordinate of the CO(2) monomer has been obtained by least-squares fitting new ab
      initio interaction energies to a new three-dimensional Morse/Long-Range (3D-MLR)
      potential function form. This fit to 2832 points has a root-mean-square (RMS)
      deviation of 0.032 cm(-1) and requires only 55 parameters. The resulting pure ab
      initio potential provides a good representation of the experimental microwave and
      infrared data: for 51 pseudo microwave and 49 infrared transitions the RMS
      discrepancies are 0.0110 and 0.0445 cm(-1), respectively. Scaling this surface
      using only two morphing parameters yields an order of magnitude better agreement
      with experiments, with RMS discrepancies of only 0.0025 and 0.0038 cm(-1),
      respectively. The calculated infrared band origin shift associated with the nu(3)
      fundamental of CO(2) is 0.109 cm(-1), in good agreement with the (extrapolated)
      experimental value of 0.095 cm(-1).

PMID- 18612517
TI  - A microwave spectroscopic and quantum chemical study of propa-1,2-dienyl
      selenocyanate (H(2)==C==CHSeC[triple bond]N) and cyclopropyl selenocyanate
      (C(3)H(5)SeC[triple bond]N).
AB  - The microwave spectra of propa-1,2-dienyl selenocyanate, H(2)C==C==CHSeC[triple
      bond]N, and cyclopropyl selenocyanate, C(3)H(5)SeC[triple bond]N, are reported.
      The spectra of the ground and two vibrationally excited states of the (80)Se
      isotopologue and the spectrum of the ground state of the (78)Se isotopologue were
      assigned for one rotameric form of H(2)C==C[double bond, length as m
      dash]CHSeC[triple bond]N. This conformer is characterized by a C-C-Se-C dihedral
      angle of 129(5) degrees from synperiplanar (0 degrees ) and is shown to be the
      global minimum of H(2)C[double bond, length as m-dash]C[double bond, length as m
      dash]CHSeC[triple bond]N. The spectra of the ground and of three vibrationally
      excited states of the (80)Se isotopologue, as well as of the ground state of the
      (78)Se isotopologue of one rotamer of C(3)H(5)SeC[triple bond]N were assigned.
      This conformer has a H-C-Se-C dihedral angle of 80(4) degrees from synperiplanar
      and is at least 3 kJ mol(-1) more stable than any other form of the molecule. The
      microwave study has been augmented by quantum chemical calculations at the
      B3LYP/6-311+ +G(3df,3pd) and MP2/6-311+ +G(3df,3pd) levels of theory.

PMID- 18612518
TI  - Bi-analyte SERS with isotopically edited dyes.
AB  - Isotopically substituted rhodamine dyes provide ideal probes for the study of
      single-molecule surface enhanced Raman scattering (SM-SERS) events through
      multiple-analyte techniques. Isotopic editing should, in principle, provide
      probes that have identical chemical properties (and surface chemistries); while
      exhibiting at the same time distinct Raman features which enable us to identify
      single-molecule SERS events. We present here a specific example of two-analyte SM
      SERS based on the isotopic substitution of a methyl ester rhodamine dye. The dyes
      are carefully characterized (in both standard and SERS conditions) to confirm
      experimentally their similar chemical properties. We then demonstrate their
      utility for bi-analyte SERS (BiASERS) experiments and, as an example, highlight
      the transition from a single, to a few, to many molecules in the statistics of SM
      SERS signals.

PMID- 18612519
TI  - Micro-Raman study on the conformation behavior of succinate in supersaturated
      sodium succinate aerosols.
AB  - Micro-Raman spectra of supersaturated aerosols of sodium succinate were obtained.
      The conformation behavior of the succinate dianion as a function of relative
      humidity (RH) was investigated by combining micro-Raman spectroscopy with
      theoretical calculations. A shoulder at 968 cm(-1) of the v(C-CO(2)(-)) band on
      the rise in more concentrated droplets was believed indicative of conformation
      transformations. The intensity ratio (I(963)/I(997)) of the v(C-CO(2)(-)) band at
      963 cm(-1) to the v(C-C) band at 997 cm(-1), versus the molar water-to-solute
      ratio (WSR), was used to fathom the equilibrium between gauche and trans
      conformations. Before saturation (WSR = 25.8) for the droplets, the ratio of
      I(963)/I(997) retains a value of approximately 2.6 independent of WSR, indicating
      that the equilibrium was not disturbed in the dilute droplets. In supersaturated
      droplets (WSR < 25.8), however, the ratio sharply decreases from approximately
      2.6 to approximately 1.1 at WSR = 9.6, which was attributed to the formation of
      contact ion pairs (CIPs).

PMID- 18612520
TI  - Rate constants for the gas-phase reactions of OH radicals with E-7-tetradecene, 2
      methyl-1-tridecene and the C(7)-C(14) 1-alkenes at 295 +/- 1 K.
AB  - Rate constants for the gas-phase reactions of OH radicals with the C(7)-C(14) 1
      alkenes and with E-7-tetradecene and 2-methyl-1-tridecene have been measured at
      295 +/- 1 K and atmospheric pressure of air using a relative rate technique. The
      rate constants obtained (in units of 10(-11) cm(3) molecule(-1) s(-1)) were: 1
      heptene, 3.86 +/- 0.12; 1-octene, 4.14 +/- 0.08; 1-nonene, 4.32 +/- 0.05; 1
      decene, 4.61 +/- 0.14; 1-undecene, 4.79 +/- 0.11; 1-dodecene, 5.03 +/- 0.13; 1
      tridecene, 5.09 +/- 0.17; 1-tetradecene, 4.96 +/- 0.28; E-7-tetradecene, 7.47 +/-
      0.53; and 2-methyl-1-tridecene, 8.69 +/- 0.27, where the indicated errors are two
      least-squares standard deviations and do not include the uncertainty associated
      with the rate constant for the reference compound alpha-pinene. While our rate
      constants for 1-octene and 1-nonene agree with those at 298 K recently measured
      using an absolute rate method, our rate constants for 1-decene and 1-undecene are
      lower by factors of 1.5 and 2.6, respectively. Combined with previous rate
      constants from this laboratory for the C(4)-C(7) 1-alkenes, our data show that
      the rate constants for the reactions of OH radicals with 1-alkenes increase
      linearly with increasing carbon number, with the increase per additional CH(2)
      group being a factor of approximately 1.4-1.5 higher than that observed in the n
      alkane series. The rate constants measured for E-7-tetradecene and 2-methyl-1
      tridecene suggest that the increase in rate constant per additional CH(2) group
      ranges from being similar to that in the n-alkanes series to being a factor of
      approximately 2 higher.

PMID- 18612521
TI  - Revealing complex formation in acetone-n-alkane mixtures by MAS PFG NMR diffusion
      measurement in nanoporous hosts.
AB  - Magic-angle spinning pulsed field gradient nuclear magnetic resonance (MAS PFG
      NMR) was applied for selective self-diffusion measurements of acetone-n-alkane
      (C(6) up to C(9)) mixtures in nanoporous silica gel. Two specimens of silica gel
      with mean pore sizes of about 4 and 10 nm are considered. In the smaller pores,
      the n-alkane diffusivities are by about one and the acetone diffusivities by
      about two orders of magnitude smaller than in the larger pores. In addition, the
      acetone diffusivities in the narrow-pore specimen exhibit a pronounced
      oscillation with increasing chain length of the solvent n-alkanes: the
      diffusivities of acetone dissolved in odd-carbon number n-alkanes exceed those of
      acetone dissolved in even-carbon number n-alkanes by about 50%! These findings
      reproduce the tendencies observed in previous macroscopic release studies (Phys.
      Chem. Chem. Phys. 2003, 5, 2476) and suggest the formation of acetone-n-alkane
      complex-like assemblages in the narrow-pore silica gel.

PMID- 18612522
TI  - Chemically bound gold nanoparticle arrays on silicon: assembly, properties and
      SERS study of protein interactions.
AB  - A highly reproducible and facile method for formation of ordered 2 dimensional
      arrays of CTAB protected 50 nm gold nanoparticles bonded to silicon wafers is
      described. The silicon wafers have been chemically modified with long-chain
      silanes terminated with thiol that penetrate the CTAB bilayer and chemically bind
      to the underlying gold nanoparticle. The silicon wafer provides a reproducibly
      smooth, chemically functionalizable and non-fluorescent substrate with a silicon
      phonon mode which may provide a convenient internal frequency and intensity
      calibration for vibrational spectroscopy. The CTAB bilayer provides a potentially
      biomimetic environment for analyte, yet allows a sufficiently small nanoparticle
      separation to achieve a significant electric field enhancement. The arrays have
      been characterized using SEM and Raman spectroscopy. These studies reveal that
      the reproducibility of the arrays is excellent both between batches (<10% RSD)
      and across a single batch (<5% RSD). The arrays also exhibit good stability, and
      the effect of temperature on the arrays was also investigated. The interaction of
      protein and amino acid with the nanoparticle arrays was investigated using Raman
      microscopy to investigate their potential in bio-SERS spectroscopy. Raman of
      phenylalanine and the protein bovine pancreatic trypsin inhibitor, BPTI were
      studied using 785 nm excitation, coincident with the surface plasmon absorbance
      of the array. The arrays exhibit SERS enhancements of the order of 2.6 x 10(4)
      for phenylalanine, the standard deviation on the relative intensity of the 1555
      cm(-1) mode of phenylalanine is less than 10% for 100 randomly distributed
      locations across a single substrate and less than 20% between different
      substrates. Significantly, comparisons of the Raman spectra of the protein and
      phenylalanine in solution and immobilized on the nanoparticle arrays indicates
      that the protein is non-randomly orientated on the arrays. Selective SERS
      enhancements suggest that aromatic residues penetrate through the bilayer
      inducing conformational changes in the protein.

PMID- 18612523
TI  - A combined theoretical-experimental study on the acidity of WO(x)-ZrO(2) systems.
AB  - This work provides a chemical approach to the relationship between structure and
      electronic behavior of the active surface of the WO(x)-ZrO(2) system as a
      function of W loads. This study shows that the electronic hardness (eta), the
      Lewis and Bronsted acidity are functions of the local coordination and of the
      polymerization degree of the WO(x) domain. From theoretical calculations the
      observed behavior in the WO(x)-ZrO(2) system is explained: the Bronsted acidity
      increases while the Lewis acidity decreases as the W centers go from tetrahedral
      to octahedral coordination and as the condensation degree of the WO(x) domain
      increases. Our results also indicate that not all the Bronsted sites in the WO(x)
      domains are equally acid, and that as the W load increases the most acid sites
      decrease in number due to the condensation process. This finding also means a
      decrease on the average acidity per H site. Additionally, our results suggest
      that for surface densities in the 4-7 W nm(-2) range, mainly dimeric-tungstate
      species are present. A maximum in Bronsted acidity was observed for a W surface
      density about 7 W nm(-2).

PMID- 18612524
TI  - Interaction of acetonitrile with Na-zeolites: adsorption modes and vibrational
      dynamics in the zeolite channels and cavities.
AB  - The interaction of acetonitrile with the extra-framework Na(+) cations in
      zeolites, namely Na-LTA and Na-FER, was investigated. The relative stabilities of
      possible types of adsorption complexes were calculated at the periodic DFT level.
      Individual effects on the complex stability and on the vibrational dynamics of
      adsorbed acetonitrile were qualitatively analysed on various cluster models. The
      acetonitrile primarily interacts with the Na(+) cation (via the N end), and the
      complex stability is modulated by the interaction of the methyl group with the
      framework oxygen atoms, which has a partial hydrogen-bond character. In line with
      the results of recent analyses of CO interactions with metal-exchanged zeolites
      [D. Nachtigallova, O. Bludsky, C. O. Arean, R. Bulanek and P. Nachtigall, Phys.
      Chem. Chem. Phys., 2006, 8, 4849], two types of effects should be taken into
      consideration for acetonitrile complexes in Na-zeolites: (i) the effects from the
      bottom, reflecting the accessibility and coordination of the primary metal
      cation, to which the acetonitrile molecule is bonded via the N atom; and (ii) the
      effects from the top, including H-bond formation (stabilising effect) or
      repulsion due to the secondary metal cation. The effect from the bottom results
      in a blue shift of nu(CN) while the effect from the top (H-bond formation)
      results in a red shift in both nu(CN) and nu(CH).

PMID- 18612525
TI  - Thrombosis and Haemostasis: volume 100 and going strong ...

PMID- 18612526
TI  - Mean platelet volume not so far from being a routine diagnostic and prognostic
      measurement.

PMID- 18612527
TI  - Newly diagnosed venous thromboembolism: which patients will bleed after
      anticoagulation is initiated?

PMID- 18612528
TI  - Beyond glucose levels in diabetic patients with coronary artery disease: platelet
      activity and non-responsiveness to antiplatelet therapy.

PMID- 18612529
TI  - The hidden sepsis marker: aPTT waveform analysis.

PMID- 18612530
TI  - Paroxysmal atrial fibrillation, stroke risk and thromboprophylaxis.

PMID- 18612531
TI  - Pro: 'Warfarin should be the drug of choice for thromboprophylaxis in elderly
      patients with atrial fibrillation'. Why warfarin should really be the drug of
      choice for stroke prevention in elderly patients with atrial fibrillation.

PMID- 18612532
TI  - Contra: 'Warfarin should be the drug of choice for thromboprophylaxis in elderly
      patients with atrial fibrillation'. Caveats regarding use of oral anticoagulant
      therapy among elderly patients with atrial fibrillation.

PMID- 18612533
TI  - Possible mechanisms contributing to oxidative inactivation of activated protein
      C: molecular dynamics study.
AB  - Activated protein C (APC) is a serine protease, an effector enzyme of the natural
      anticoagulant pathway. APC is approved for treatment of severe sepsis
      characterized by the increased concentrations of H(2)O(2) and hypochlorite. We
      found that treatment of APC with these oxidants markedly inhibits the cleavage of
      the APC-specific chromogenic substrate, suggesting that oxidants can induce
      changes in the structure of the active site of APC. Resistance of oxidant-treated
      APC to chemical digestion with cyanogen bromide (CNBr) implies that methionine
      oxidation can at least in part be responsible for inhibition of APC. Since
      methionine residues, the main targets of oxidants in APC, are not included in the
      active site, we hypothesize that oxidation induces allosteric changes in the
      architecture of the catalytic triad of APC. Using molecular dynamics (MD)
      simulations we found that methionine oxidation alters the distance between
      cSer195Ogamma and cHis57Nepsilon2 atoms placing them in positions unfavorable for
      the catalysis. At the same time, neither distances between Calpha atoms of the
      catalytic triad cAsp102-cHis57-cSer195, nor the overall structure of APC changed
      significantly after oxidation of the methionine residues. Disruption of the H
      bond between Ndelta1 of cHis57 and carboxyl group of cAsp102, which can take
      place during the hypochlorite-induced modification of cHis57, dramatically
      changed the architecture of the catalytic triad in oxidized APC. This mechanism
      could contribute to APC inactivation by hypochlorite concurrently with methionine
      oxidation. These are novel findings, which describe potentially
      pathophysiologically relevant changes in the functional stability of APC exposed
      to the oxidative stress.

PMID- 18612535
TI  - An observational study of sucrose-formulated recombinant factor VIII for Japanese
      patients with haemophilia A.
AB  - The safety and efficacy of sucrose-formulated recombinant factor VIII (rFVIII-FS;
      Kogenate FS) under usual clinical practice were evaluated for 12 months in an
      observational, postmarketing surveillance study conducted at 214 treatment
      centres throughout Japan. The study included 631 patients with haemophilia A, 80%
      of whom had severe or moderately-severe disease (< or = 2% FVIII:C). Most
      patients (n = 477; 75.6%) had >100 prior exposure days (EDs), but the study also
      included 62 (9.8%) patients with <20 EDs who were at high risk for inhibitor
      development. A total of 71,240 infusions were administered during the observation
      (mean, 113 +/- 108 per patient). Physicians rated efficacy and tolerability of
      rFVIII-FS as "very good" or "good" in >99% of patients. FVIII inhibitors were
      observed in seven patients (5 de novo; 1 persistent/fluctuating; 1 recurrent).
      The overall de novo inhibitor incidence was 0.8% (5/631; or 5/599 among the
      subgroup of patients with negative baseline titre and no known inhibitor
      history). De novo cases represented 3.2% (2/62) of patients with <20 EDs at
      enrollment (2/57 in the no inhibitor subgroup) and 0.2% (1/477) of patients
      pretreated with >100 EDs (1/452 in the no inhibitor subgroup) at enrollment. The
      results of this large observational study demonstrate that rFVIII-FS is both safe
      and efficacious as used in the usual clinical setting for the treatment of
      Japanese patients with mild to severe haemophilia A. This study supports the
      efficacy of rFVIII-FS with an incidence of inhibitor formation no greater than in
      a comparable European study or previous phase III clinical studies.

PMID- 18612534
TI  - Predictive variables for major bleeding events in patients presenting with
      documented acute venous thromboembolism. Findings from the RIETE Registry.
AB  - A score that can accurately determine the risk of major bleeding during
      anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is
      an ongoing registry of consecutive patients with acute venous thromboembolism
      (VTE). We composed a score to predict the risk for major bleeding within three
      months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were
      randomly assigned to the derivation sample, 6,572 to the validation sample. In
      the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On
      multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels
      >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently
      associated with an increased risk for major bleeding. A score was composed
      assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or
      anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%)
      patients scored 0 points (low risk); 9,645 (74%) 1-4 points (intermediate); 758
      (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95%
      confidence interval [CI]: 0.1-0.6), 2.6% (95% CI: 2.3-2.9), and 7.3% (95% CI: 5.6
      9.3), respectively. The likelihood ratio test was: 0.14 (95% CI: 0.07-0.27) for
      patients at low risk;2.96 (95% CI: 2.18-4.02) for those at high risk. In the
      validation sample the incidence of major bleeding was: 0.1%, 2.8%, and 6.2%,
      respectively. In conclusion, a risk score based on six variables documented at
      entry can identify VTE patients at low, intermediate, or high risk for major
      bleeding during the first three months of therapy.

PMID- 18612536
TI  - Absolute risk of venous and arterial thromboembolism in thrombophilic families is
      not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels.
AB  - High levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are a supposed
      risk factor for thrombosis. However, results from previous studies are
      conflicting. We assessed the absolute risk of venous and arterial thromboembolism
      in subjects with high TAFI levels (>126 U/dl) versus subjects with normal levels,
      and the contribution of other concomitant thrombophilic defects. Relatives from
      four identical cohort studies in families with either deficiencies of
      antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII
      levels, or hyperhomocysteinemia were pooled. Probands were excluded. Of 1,940
      relatives, 187 had high TAFI levels. Annual incidences of venous thromboembolism
      were 0.23% in relatives with high TAFI levels versus 0.26% in relatives with
      normal TAFI levels (adjusted relative risk [RR] 0.8; 95% confidence interval
      [CI], 0.5-1.3). For arterial thrombosis these were 0.31% versus 0.23% (adjusted
      RR 1.4; 95% CI, 0.9-2.2). High levels of factor VIII, IX and XI were observed
      more frequently in relatives with high TAFI levels. Only high factor VIII levels
      were associated with an increased risk of venous and arterial thrombosis,
      independently of TAFI levels. None of these concomitant defects showed
      interaction with high TAFI levels. High TAFI levels were not associated with an
      increased risk of venous and arterial thromboembolism in thrombophilic families.

PMID- 18612537
TI  - Phenotypic heterogeneity in the Gray platelet syndrome extends to the expression
      of TREM family member, TLT-1.
AB  - The Gray platelet syndrome (GPS) is a rare inherited disorder linked to undefined
      molecular abnormalities that prevent the formation and maturation of alpha
      granules. Here, we report studies on two patients from unrelated families that
      confirm phenotypic heterogeneity in the disease. First we used immunoelectron
      microscopy (I-EM) to confirm that TREM-like transcript-1 (TLT-1) is mostly
      localized to alpha-granule membranes of normal platelets. Then we performed
      Western blotting (WB) and flow cytometry with permeabilized platelets to show
      that TLT-1 is selectively reduced in the platelets of patient 1, previously noted
      to be deficient in glycoprotein (GP)VI (Nurden et al., Blood 2004; 104: 107-114).
      Yet both TLT-1 and GPVI were normally expressed in platelets of patient 2. Usual
      levels of JAM-C and claudin-5, also members of the immunoglobulin receptor
      family, were detected in platelets of both patients. In contrast, P-selectin was
      markedly decreased for patient 1 but not patient 2. Two metalloproteases, MMP-2
      and MMP-9 were normally present. As predicted, platelets of patient 1 showed
      little labelling for TLT-1 in I-EM, whereas residual Fg was seen in small
      vesicular structures and P-selectin lining vacuoles or channels of what may be
      elements of the surface-connected canalicular system. Our results identify TLT-1
      as a glycoprotein potentially targeted in platelets of GPS patients, while
      decreases in at least three membrane glycoproteins suggest that an unidentified
      proteolytic activity may contribute to the phenotype in some patients with this
      rare disease.

PMID- 18612538
TI  - Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus
      formation.
AB  - Salsolinol, an endogenous neurotoxin, is known to be involved in the neuropathy
      of Parkinson's disease and chronic alcoholism. In these diseases, increased
      thrombotic events are also commonly reported, yet the mechanism underlying
      remains poorly understood. Here we report that salsolinol can enhance agonist
      induced platelet aggregation and granular secretion, which is essential in the
      thrombus formation. In rat and human platelets, agonist-induced platelet
      aggregation was significantly increased by salsolinol in a concentration
      dependent manner. Agonist-induced granular secretions of serotonin and
      concomitant P-selectin expression were also augmented by salsolinol. alpha2
      adrenergic blockers attenuated the salsolinol-enhanced aggregation and the
      inhibition of cyclic AMP generation was found, suggesting the involvement of
      alpha2-adrenergic receptor-mediated pathways in these events. In accord with the
      in-vitro results, in an arterial and venous thrombosis model in vivo in the rat,
      salsolinol shortened vessel occlusion time and increased thrombus formation,
      respectively. In conclusion, we demonstrated that salsolinol can enhance agonist
      induced aggregation and granular secretion in platelets through alpha2-adrenergic
      receptor activation, which resulted in the increased thrombus formation in vivo.
      These results suggest that salsolinol-enhanced platelet aggregation could be a
      possible contributing factor to the thrombotic events observed in Parkinson's
      disease and alcoholism.

PMID- 18612539
TI  - Effects of von Willebrand factor concentration and platelet collision on shear
      induced platelet activation.
AB  - The binding of plasma von Willebrand factor (vWF) to platelet glycoprotein (GP)
      Ibalpha in a high shear stress field, and subsequent integrin-GPIIb/IIIa-vWF
      conjunction induces platelet aggregation (SIPA). However, the specific
      biomechanical mechanism of the vWF-GPIb interaction still remains to be
      elucidated. A parallel-plate rectangular flow chamber was built to simulate a
      stenopeic artery flow pattern. Using the flow chamber, we examined shear-induced
      platelet activation (SIPAct) at different vWF concentrations (5-25 microg/ml) and
      several simulated stenotic high shear rates. P-selectin expression on the
      platelets and annexin V binding to the platelets were used as two markers of
      platelet activation. At different localized shear rates (3,000 s(-1)-9,500 s(
      1)), the percentage of annexin V and P-selectin positive cells increased from 8.3
      +/- 0.4% to 22.3 +/- 1.8% ( p 0.05) and from 17.4 +/- 0.5% to 33.5 +/- 2.5% (p
      0.05), respectively. As the vWF concentration increased from 5 microg/ml to 25
      microg/ml, the annexin V binding rate increased from 7.2 +/- 0.6% to 53.4 +/-
      3.8% (p 0.05), and P-selectin expression increased from 16.5 +/- 1.2% to 65.9 +/-
      5.2% (p 0.05). A test in a uniform shear field using cone-plate viscometer
      rheometry showed that the platelet activation rate was proportional to the
      platelet concentration. This result suggests that platelet collision is one of
      the impact factors of SIPAct.

PMID- 18612540
TI  - The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic
      events during low-dose therapy with acetyl salicylic acid.
AB  - Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX
      1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T
      polymorphism of COX-1 is associated with an impaired inhibition of both
      thromboxane production and in-vitro platelet aggregation by aspirin. We studied
      whether this polymorphism is also associated with the risk of clinical thrombotic
      events in patients using aspirin. We included 496 patients admitted to our
      Coronary Care Unit for various indications treated with aspirin 80 mg daily.
      Genotyping for the C50T polymorphism demonstrated that 86.7% of the patients had
      the common genotype, and 13.3% had the variant (12.5% heterozygous, 0.8%
      homozygous). Baseline variables were well balanced, except that patients with the
      common genotype more frequently used aspirin prior to admission compared to those
      patients with the variant genotype. The composite primary endpoint of myocardial
      infarction, stroke, and/or cardiovascular death occurred in 98 patients (19.8%).
      Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and
      cardiovascular death in 12.1%. The unadjusted hazard ratio (95% CI) for the
      primary endpoint for patients with the variant versus the common genotype was
      1.07 (0.62-1.85), p = 0.8. The adjusted hazard ratio was 0.86 (0.49-1.50), p =
      0.6. In prior laboratory studies the COX-1 C50T polymorphism was associated with
      an impaired inhibitory effect of aspirin on thromboxane production and platelet
      function. However, in this cohort of patients using low-dose aspirin for
      secondary prevention the polymorphism was not associated with a higher risk of
      atherothrombotic events.

PMID- 18612541
TI  - Baseline platelet activity and response after clopidogrel in 257 diabetics among
      822 patients with coronary artery disease.
AB  - The objective was to describe the indices of platelet aggregation and activation
      in a large cohort of diabetic patients with coronary artery disease (CAD).
      Recently, a number of observations have indicated that patients with diabetes
      mellitus (DM) exhibit persistent platelet activation, and low response after
      antiplatelet therapy, although no randomized data exist. We sought to define the
      baseline platelet biomarkers, and the patterns of response to aspirin and
      clopidogrel therapy in DM versus non-diabetic patients. Secondary post-hoc
      analyses were made of platelet activity biomarkers in the dataset which consisted
      of patients with documented CAD (n = 822), including those with DM (n = 257).
      Patients with DM exhibited higher baseline platelet activity by adenosine
      diphosphate (ADP)- (p = 0.0002), and collagen-induced (p = 0.03) aggregometry;
      Ultegra- (p = 0.0001), and PFA-100 (p = 0.02) analyzers; and expression of
      platelet/endothelial cell adhesion molecule-1 (PECAM-1) (p = 0.01), glycoprotein
      (GP) IIb/IIIa antigen (p = 0.001), and activity (p = 0.02), vitronectin receptor
      (p = 0.03), P selectin (p = 0.02), and intact epitope of PAR-1 thrombin receptor
      (p = 0.02). Antiplatelet response after clopidogrel in diabetics was impaired
      when compared with non-diabetics. In conclusion, diabetic patients exhibit high
      pretreatment platelet activity, and do not respond well to the available
      antiplatelet regimens when compared with similar patients without DM. The
      clinical implications of these findings are unknown but are potentially
      important. Considering worsened outcomes in this high-risk population, clinical
      trials in DM are urgently needed in order to define the optimal degree of
      platelet inhibition and suitability for more aggressive antiplatelet regimens.

PMID- 18612542
TI  - Increased platelet sensitivity among individuals with aspirin resistance -
      platelet aggregation to submaximal concentration of arachidonic acid predicts
      response to antiplatelet therapy.
AB  - Aspirin 'resistance' (AR) is a phenomenon of uncertain etiology describing
      decreased platelet inhibition by aspirin. We studied whether (i) platelets in AR
      demonstrate increased basal sensitivity to a lower degree of stimulation and (ii)
      platelet aggregation with submaximal stimulation could predict responses to
      aspirin. Serum thromboxane B(2) (TxB(2)) levels and platelet aggregation with
      light transmission aggregometry (LTA) were measured at baseline and 24 hours
      after 325 mg aspirin administration in 58 healthy subjects. AR was defined as the
      upper sixth of LTA (> or = 12%) to 1.5 mM AA. Baseline platelet aggregation with
      submaximal concentrations of agonists [ADP 2 microM, arachidonic acid (AA) 0.75
      mM, collagen 0.375 and 0.5 microg/ml] was greater in AR subjects compared with
      non-AR subjects, but not with higher concentrations (ADP 5 microM and 20 microM,
      AA 1.5 mM and collagen 1 microg/ml). Post-aspirin platelet aggregation was
      elevated in AR subjects with both submaximal and maximal stimulation. Baseline
      and post-aspirin serum TxB(2) were higher in AR subjects and decreased further
      with ex-vivo COX-1 inhibition, suggesting incompletely suppressed COX-1 activity.
      Pre-aspirin platelet aggregation to 0.75 AA demonstrated a dichotomous response
      with 29/58 subjects having aggregation < or = 15% and 29/58 subjects having
      aggregation > or = 75%. In the high aggregation group 28% had AR compared to 6%
      in the non-AR group (p = 0.04). In conclusion, platelets in AR subjects
      demonstrate increased basal sensitivity to submaximal stimulation, which could
      predict responses to antiplatelet therapy.

PMID- 18612543
TI  - Immune complex-mediated glomerulonephritis is ameliorated by thrombin-activatable
      fibrinolysis inhibitor deficiency.
AB  - The activity of plasmin plays a critical role in the development of chronic
      glomerulonephritis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a
      potent inhibitor of plasmin generation. We hypothesized that TAFI is involved in
      the pathogenesis of glomerulonephritis because it inhibits plasmin generation. To
      demonstrate this hypothesis, we compared the development of immune complex
      mediated glomerulonephritis in wild-type and TAFI-deficient mice. After six weeks
      of treatment with horse spleen apoferritin and lipoplysaccharide to induce
      glomerulonephritis, mice deficient in TAFI had significantly better renal
      function as shown by lower concentrations of albumin in urine and blood urea
      nitrogen compared to wild-type mice. In addition, the activity of plasmin and
      matrix metalloproteinases was significantly increased, and mesangial matrix
      expansion and the deposition of collagen and fibrin in kidney tissues were
      significantly decreased in TAFI-knockout mice as compared to their wild-type
      counterparts. Depletion of fibrinogen by batroxobin (Defibrase) treatment led to
      equalization of the renal function and the amount of collagen deposition in the
      kidneys of TAFI-knockout and wild-type mice with immune complex-mediated
      glomerulonephritis. Together these observations suggest that TAFI-mediated
      inhibition of plasmin generation plays a role in the pathogenesis of
      glomerulonephritis, and that it may constitute a novel molecular target for the
      therapy of this disease.

PMID- 18612545
TI  - Potential protective role of apoprotein J (clusterin) in atherogenesis: binding
      to enzymatically modified low-density lipoprotein reduces fatty acid-mediated
      cytotoxicity.
AB  - Following entrapment in the arterial intima, low-density lipoprotein (LDL) can be
      modified by hydrolytic enzymes to yield a lipoprotein derivative that binds C
      reactive protein, activates complement, and is rapidly taken up by
      monocytes/macrophages. Free fatty acids contained in enzymatically modified LDL
      (E-LDL) render the lipoprotein cytotoxic due to their capacity to trigger
      programmed cell death. Apoprotein J (ApoJ) alias clusterin is a multifunctional
      glycoprotein with cytoprotective and anti-inflammatory properties. It interacts
      with diverse substrates, is present in the intima and the media of arteries with
      atherosclerotic lesions and is also synthesized by smooth muscle cells during
      development of atherosclerosis. We report that ApoJ binds to E-LDL but not to
      native LDL. Binding resulted in marked reduction of cytotoxicity of E-LDL on
      smooth muscle cells, as revealed by determination of caspase activity, annexin
      binding, and cellular ATP. ApoJ was detected immunohistochemically in early
      atherosclerotic lesions, where it was found to co-localize with E-LDL. In
      atherosclerotic lesions, ApoJ may thus subserve protective functions through its
      capacity to inactivate C5b-9 complement complexes and by reducing the cytotoxic
      effects of modified LDL on cells that gain contact with the lipoprotein.

PMID- 18612544
TI  - Protease activated receptor 1 (PAR-1) activation by thrombin is protective in
      human pulmonary artery endothelial cells if endothelial protein C receptor is
      occupied by its natural ligand.
AB  - We recently demonstrated that the occupancy of endothelial protein C receptor
      (EPCR) by its natural ligand activated protein C (APC)/protein C switches the
      protease activated receptor 1 (PAR-1)-dependent signaling specificity of thrombin
      from a disruptive to a protective effect in cultured human umbilical vein
      endothelial cells. Given the phenotypic differences between endothelial cells in
      venular and arterial beds, in this study we evaluated the signaling function of
      thrombin in human pulmonary artery endothelial cells (HPAECs) before and after
      treating them with PC-S195A which lacks catalytic activity but exhibits a normal
      affinity for EPCR. As expected, both thrombin and thrombin receptor agonist
      peptide (TRAP) enhanced the permeability barrier of HPAECs; however, both PAR-1
      agonists exhibited a potent barrier protective effect when the cells were treated
      with PC-S195A prior to stimulation by the agonists. Interestingly, similar to
      APC, thrombin exhibited a potent cytoprotective activity in the LPS-induced
      permeability and TNF-alpha-induced apoptosis and adhesion assays in the PC-S195A
      treated HPAECs. Treatment of HPAECs with the cholesterol depleting molecule
      methyl-beta-cyclodextrin eliminated the protective effect of both APC and
      thrombin. These results suggest that the occupancy of EPCR by its natural ligand
      recruits PAR-1 to a protective signaling pathway within lipid rafts of HPAECs.
      Based on these results we conclude that the activation of PAR-1 by thrombin would
      initiate a protective response in intact arterial vascular cells expressing EPCR.
      These findings may have important ramifications for understanding the mechanism
      of the participation of the vascular PAR-1 in pathophysiology of the inflammatory
      disorders.

PMID- 18612546
TI  - Prostacyclin induction by high-density lipoprotein (HDL) in vascular smooth
      muscle cells depends on sphingosine 1-phosphate receptors: effect of simvastatin.
AB  - Prostacyclin (PGI2) is an important regulator of vascular homeostasis. Our goal
      was to analyze the role of sphingosine 1-phosphate (S1P) and its receptors in the
      up-regulation of cyclooxygenase-2 (Cox-2) induced by HDL in human vascular smooth
      muscle cells (VSMC). S1P induces Cox-2 expression in a time-and dose-dependent
      manner at concentrations (0.02-1 microM) compatible with those present in
      physiological HDL levels. The effect was mimicked by dihydro-S1P (DhS1P), a S1P
      derivative that only acts through cell surface S1P receptors. Desensitization of
      S1P receptors with S1P (or DhS1P) abolished HDL-induced Cox-2 up-regulation and
      PGI2 release. Inhibition of S1P receptors by suramin (inhibitor of S1P3), JTE013
      (inhibitor of S1P2) or VPC23019 (inhibitor of S1P1 and S1P3) reduced the up
      regulation of Cox-2 induced by HDL and S1P. The combination of suramin and JTE013
      increased the inhibitory effect compared to that observed in cells treated with
      each inhibitor alone. siRNA against S1P2 or S1P3 significantly reduced the
      ability of HDL and S1P to up-regulate Cox-2. Simvastatin induced over-expression
      of S1P3 and potentiated the induction of Cox-2 expression produced by HDL (or
      S1P). Finally, suramin, JTE013 and VPC23019 inhibited p38 MAPK and ERK1/2
      signaling pathways activated by HDL (or S1P) and the downstream activation of
      CREB, a key transcription factor involved in Cox-2 transcriptional up-regulation.
      These results indicate that S1P receptors, in particular S1P2 and S1P3, are
      involved in the Cox-2-dependent effects of HDL on vascular cells. Strategies
      aimed to therapeutically modulate S1P or S1P receptors could be useful to improve
      cardiovascular protection.

PMID- 18612547
TI  - Formation of tissue factor-factor VIIa-factor Xa complex induces activation of
      the mTOR pathway which regulates migration of human breast cancer cells.
AB  - Tissue factor (TF) is a transmembrane glycoprotein that initiates blood
      coagulation when complexed with activated factor VII (FVIIa). TF is
      constitutively expressed in a variety of tumor cells and has been implicated in
      cellular signaling, angiogenesis, and tumor progression. Formation of TF-FVIIa
      complex and generation of downstream coagulation proteases, including activated
      factor X (FXa) and thrombin, initiate signaling by activation of protease
      activated receptors (PARs). We have previously shown that TF-FVIIa-Xa complex
      formation promotes phosphorylation of p44/42 mitogen-activated protein kinase and
      Akt/protein kinase B in human breast cancer cells. In the present study, we show
      that formation of TF-FVIIa-FXa complex induces phosphorylation of mammalian
      target of rapamycin (mTOR) and p70 S6 kinase in a human breast cancer cell line,
      Adr-MCF-7. Activation of the mTOR pathway, which is probably mediated by PAR1
      and/or PAR2, was associated with enhanced cell migration, a key step in the
      metastatic cascade. Inhibition of this pathway with the specific mTOR inhibitor,
      rapamycin, markedly decreased cell migration induced by formation of TF-FVIIa-FXa
      complex. These studies suggest that TF-FVIIa-mediated signaling modulates mTOR
      pathway activation, which regulates in part breast cancer cell migration.
      Targeting the TF-mediated cell signaling pathway might represent a novel strategy
      for the treatment of breast cancer.

PMID- 18612548
TI  - An evaluation of methods for determining reference intervals for light
      transmission platelet aggregation tests on samples with normal or reduced
      platelet counts.
AB  - Light transmission platelet aggregation tests are important for diagnosing
      platelet function defects. However, uncertainties exist about the best procedures
      to determine aggregation reference intervals. We investigated methods for
      determining reference intervals for light transmission aggregation tests, using
      the % maximal aggregation values for prospectively collected data on healthy
      control samples. Reference intervals for samples tested at 250 x 10(9)
      platelets/l were determined by mean +/- 2 standard deviations and non-parametric
      analyses. To establish reference intervals for tests on thrombocytopenic
      subjects, regression analyses were used to estimate 95% confidence limits for %
      maximal aggregation, according to sample platelet counts, using data for control
      samples diluted to match the platelet count of undiluted thrombocytopenic patient
      platelet-rich plasma samples. For samples tested at 250 x 10(9) platelets/l, non
      parametric analyses described 95% of data for healthy control samples better than
      mean +/- 2 standard deviations. For samples tested at lower counts, to match
      thrombocytopenic samples, the % maximal aggregation was influenced by platelet
      count and derived limits were wider at very low platelet counts for almost all
      agonists. With ristocetin, it proved feasible to test samples with very low
      platelet counts to exclude Bernard-Soulier syndrome and type 2B von Willebrand
      disease. Non-parametric analyses should be the preferred method to establish
      light transmission aggregation reference intervals for samples tested at normal
      platelet counts. The derived limits for thrombocytopenic samples provide guidance
      for evaluating thrombocytopenic platelet function disorders, including which
      agonists to test, based on the sample platelet count.

PMID- 18612549
TI  - The biphasic transmittance waveform: an early marker of sepsis in patients with
      neutropenia.
AB  - Transmittance waveform (TW) analysis has been proposed as a method of both
      prediction and monitoring of non-overt and overt disseminated intravascular
      coagulation. This study assessed the use of the rapidTW of the activated partial
      thromboplastin time in the detection of sepsis in 49 consecutive neutropenic
      haemato-oncology patients. A slope 1 cut-off value of -0.050 was found to be
      optimum giving 85% sensitivity with 92% specificity and positive and negative
      predictive values of 62% and 98%, respectively. Furthermore a worsening slope 1
      value at 24 hours was indicative of a 60% increase in mortality risk. Haemato
      oncology patients have a significantly increased risk of developing sepsis during
      intensive chemotherapy, exacerbated by the resultant neutopenia. This sepsis may
      progress extremely rapidly and is associated with a high mortality. Early
      diagnosis is therefore critical and is currently made on a predominantly clinical
      basis with supporting microbiological evidence 2-3 days later. This study showed
      that TW offers an early marker, predictive of sepsis in neutropenic patients. It
      correlates with subsequent microbiological results and may identify patients at
      greater risk of clinical deterioration who may require more intensive early
      therapy or observation. It may also provide a useful marker to monitor the
      effects of treatment.

PMID- 18612550
TI  - Temporarily successful eradication therapy in acquired haemophilia with high
      inhibitor titer: a case report with a new protocol.

PMID- 18612551
TI  - Treatment of acquired thrombotic thrombocytopenic purpura (TTP) with plasma
      infusion plus rituximab.

PMID- 18612552
TI  - Treatment of midgestational placental haemorrhage with recombinant factor VIIa.

PMID- 18612553
TI  - Intoxication with three different superwarfarin compounds in an adult woman.

PMID- 18612554
TI  - Factor XI protein in human pancreas and kidney.

PMID- 18612555
TI  - Heparin is procoagulant in the absence of antithrombin.

PMID- 18612556
TI  - Hereditary haemorrhagic telangiectasia (HHT): negotiating between the Scylla of
      bleeding and Charybdis of thrombosis.

PMID- 18612557
TI  - Inter-observer reliability of measures to assess the post-thrombotic syndrome.

PMID- 18612558
TI  - Prophylaxis of upper limb deep vein thrombosis in cancer patients with central
      vein catheter.

PMID- 18612559
TI  - Fondaparinux-related thrombocytopenia in a patient with former HIT. Response to
      Rota et al. (Thromb Haemost 2008; 99: 779-781).

PMID- 18612561
TI  - Prevalence of respiratory symptoms, features of asthma, and characteristics
      associated with respiratory disease, in 6-11 year olds in Manchester.
AB  - AIMS: This paper describes the prevalence of respiratory symptoms, features of
      asthma, and characteristics associated with respiratory disease in 6-11 year old
      children in an historical cohort study. METHODS: The study included 5086
      children, all born in the same maternity unit in the north west of England over a
      four-year period. The prevalence of respiratory symptoms, features of asthma, and
      characteristics associated with respiratory disease were determined by the use of
      parent-completed questionnaires. Skin prick tests were used to ascertain atopic
      status. RESULTS: The response was 47.5%. The prevalence of wheeze, asthma
      medication use and atopic sensitisation were 20.3%, 16.2% and 37.1% respectively.
      Wheeze and atopy were significantly more prevalent in boys (22.4% versus 17.9%
      and 43.0% versus 29.3%, respectively). CONCLUSIONS: This study identified a high
      prevalence of respiratory disease in this population and provides a baseline for
      monitoring trends in respiratory disease in 6-11 year old children.

PMID- 18612562
TI  - What we have learned from the Harvard School Of Public Health College Alcohol
      Study: focusing attention on college student alcohol consumption and the
      environmental conditions that promote it.
AB  - The Harvard School of Public Health College Alcohol Study surveyed students at a
      nationally representative sample of 4-year colleges in the United States four
      times between 1993 and 2001. More than 50,000 students at 120 colleges took part
      in the study. This article reviews what we have learned about college drinking
      and the implications for prevention: the need to focus on lower drink thresholds,
      the harms produced at this level of drinking for the drinkers, the secondhand
      effects experienced by other students and neighborhood residents, the continuing
      extent of the problem, and the role of the college alcohol environment in
      promoting heavy drinking by students. In particular, the roles of campus culture,
      alcohol control policies, enforcement of policies, access, availability, pricing,
      marketing, and special promotions of alcohol are highlighted.

PMID- 18612563
TI  - Do substance type and diagnosis make a difference? A study of remission from
      alcohol- versus drug-use disorders using the National Epidemiologic Survey on
      Alcohol and Related Conditions.
AB  - OBJECTIVE: This study examined rates of remission from substance-use disorders
      based on type of disorder (abuse vs dependence), type of substance (alcohol vs
      other drug), and polysubstance involvement (alcohol or drug vs alcohol and drug).
      METHOD: Participants in the National Epidemiologic Survey on Alcohol and Related
      Conditions were included if they met criteria for a prior-to-past-year alcohol-
      and/ or drug-use disorder (N = 12,297). Odds ratios were computed to examine
      differences in the rate of remission as of the past year. RESULTS: Individuals
      with a prior-to-past-year diagnosis of abuse were more likely to be remitted,
      compared with those with a diagnosis of dependence. Individuals with both prior
      to-past-year alcohol- and drug-use disorders were less likely to be remitted,
      compared with those with only an alcohol- or drug-use disorder. No differences
      were observed in remission rates comparing individuals with a prior-to-past-year
      alcohol-use disorder with those with a drug-use disorder. CONCLUSIONS: The
      findings support prior research in suggesting a worse prognosis for individuals
      with a diagnosis of dependence and problematic use of both alcohol and drugs. In
      contrast with results from treatment samples, these general population data
      indicate that alcohol-use and drug-use disorders have a similar prognosis.

PMID- 18612564
TI  - The factor structure and severity of DSM-IV alcohol abuse and dependence symptoms
      in psychiatric outpatients.
AB  - OBJECTIVE: The goal of the present study was to examine the factor structure and
      estimated severity of alcohol-use disorder (AUD) symptoms in a sample of
      treatment-seeking psychiatric outpatients. METHOD: Participants (n = 1,027; 51.2%
      women) met the screening criteria for the lifetime assessment of AUDs according
      to the Structured Clinical Interview for the DSM-IV (SCID-I/P; First et al.,
      1995) and as a result completed an assessment of alcohol abuse and dependence
      symptoms. The average (SD) age of the sample was 36.6 (11.4) years, and 71% of
      participants met lifetime DSM-IV criteria for an AUD. RESULTS: Exploratory factor
      analysis of the tetrachoric correlation matrix of alcohol abuse and dependence
      criteria revealed that a single factor best accounted for the data in this
      sample. Results of Rasch model analyses indicated that the severity ordering of
      the DSM-IV abuse and dependence symptoms was not consistent with the hierarchical
      structure suggested by the DSM-IV. Instead, abuse items were found to be spread
      across a full range of the AUD continuum and were not consistently in the lower
      ranges of severity. CONCLUSIONS: This study extends the literature by examining a
      treatment-seeking psychiatric outpatient sample and using a semistructured
      diagnostic interview administered by mental health professionals. Methodological
      considerations and implications for the conceptualization of AUD are discussed.

PMID- 18612565
TI  - Prenatal alcohol use: the role of lifetime problems with alcohol, drugs,
      depression, and violence.
AB  - OBJECTIVE: The purpose of this study was to examine a broader array of lifetime
      factors that theoretically may be associated with prenatal alcohol use than have
      previously been studied together, including family history of alcohol-use
      problems, history of physical or sexual abuse, lifetime major depressive
      disorder, alcohol-use disorder, illicit-drug-use problems, and partner violence.
      METHOD: A total of 186 pregnant women, all of whom used alcohol in the year
      before pregnancy, were initially recruited in prenatal care settings. Women who
      reported no prenatal alcohol use (n = 96) were compared with women who drank 1-10
      standard drinks during pregnancy (n = 75) and with women who drank more than 10
      standard drinks during pregnancy (n = 13), considered to be a higher risk group,
      on the lifetime risk variables. Because of the public health implications,
      secondary analyses compared women who abstained during pregnancy with those who
      used any alcohol. RESULTS: Significant intercorrelations were found among most of
      the lifetime risk factors studied. Multivariate analyses showed that drug-use
      problems and partner violence were most strongly associated with prenatal alcohol
      use than any other variable studied. CONCLUSIONS: Consistent with a life span
      risk framework for alcohol-use problems, results of this study show that
      childhood abuse, familial alcoholism, lifetime major depressive disorder, and
      alcohol- and drug-use problems are interrelated. However, when considered
      together, only lifetime partner violence and drug use are significantly related
      to various levels of prenatal alcohol use. Identification, assessment, and
      intervention efforts should integrate these important factors.

PMID- 18612566
TI  - Universal or targeted screening for fetal alcohol exposure: a cost-effectiveness
      analysis.
AB  - OBJECTIVE: In this article, we compared the costs of testing meconium for alcohol
      exposure in newborns with the lifetime benefits of early detection and
      intervention. METHOD: A decision analytic model was developed to assess the cost
      effectiveness of testing meconium for two scenarios: (1) all infants in the
      Canadian province of Ontario and (2) infants who have an older sibling diagnosed
      with fetal alcohol spectrum disorder (FASD). The model incorporated the costs of
      early screening, early intervention, and the lifetime societal benefits of early
      intervention. RESULTS: The cost of the meconium test is Can. $150. The lifetime
      societal cost of the disease is Can. $1.3 million per incident case. The benefit
      of early intervention is an improvement in literacy, which improves the quality
      of life parameter by 0.17 and increases adult lifetime earnings by $26,400 per
      year. The ratio of the incremental cost to the incremental benefits results in an
      incremental cost-effectiveness ratio for mandating a universal screen of all
      newborns in Ontario of $65,874 per quality-adjusted life years. When considering
      targeted screening, there is a cost savings for society and improvements in
      quality of life. CONCLUSIONS: Depending on society's willingness-to-pay threshold
      for improving infants' lives in a setting of considerable equity concerns,
      universal screening and targeted screening of infants who have an older sibling
      diagnosed with FASD both represent policies that are good value for the money.

PMID- 18612568
TI  - Growing up in a permissive household: what deters at-risk adolescents from heavy
      drinking?
AB  - OBJECTIVE: This study identified psychosocial factors that may deter adolescents
      living in permissive households from heavy drinking in Grades 9 and 11. METHOD:
      Longitudinal data were obtained from 710 youth who completed surveys from Grades
      7 to 11. Permissive household was defined based on adolescent reports of whether
      the parents (1) would be upset if the adolescent drank or used marijuana, (2)
      knew their child's whereabouts when the adolescent was away from home, and (3)
      set curfews. Frequency of heavy drinking in the last 30 days was the number of
      days the adolescent had at least three alcoholic drinks. RESULTS: Three quarters
      of adolescents from permissive households reported heavy drinking at Grade 9,
      with less frequent heavy drinking among those who concurrently reported less
      exposure to peer and adult drinking, less peer approval of drinking, weaker
      positive beliefs about drinking, a stronger academic orientation, higher
      resistance self-efficacy, and less delinquency. Further, social influences and
      alcohol beliefs predicted the frequency of heavy drinking 2 years later among
      adolescents from permissive households. Although most of these factors were also
      relevant for adolescents from nonpermissive households, social influences,
      alcohol beliefs and resistance self-efficacy were stronger predictors of heavy
      drinking at Grade 9 among youth from permissive households. CONCLUSIONS: Growing
      up in a permissive household was associated with heavy drinking. Nonetheless,
      several psychosocial factors were associated with less frequent heavy drinking
      even within this at-risk population. Alcohol prevention programs that target pro
      drinking peer and adult influences, positive attitudes toward drinking, and
      resistance self-efficacy may be particularly important in deterring heavy
      drinking among adolescents living in permissive households.

PMID- 18612569
TI  - Alcohol-attributable fraction for injury in the U.S. general population: data
      from the 2005 National Alcohol Survey.
AB  - OBJECTIVE: Although studies of patients seen in emergency department (ED)
      settings have documented a strong association of alcohol with injury, such
      patients are not necessarily representative of the larger population, and less is
      known of alcohol's association with risk of injury in patient samples outside the
      ED. METHOD: Drinking before injury was analyzed in the 2005 National Alcohol
      Survey among the 1,149 respondents (18.5%, weighted) who reported an injury
      during the past year; analysis was by injury treatment type (ED-treated, 29.2%;
      other-treated, 47.8%; and nontreated, 22.9%). RESULTS: Based on case-crossover
      analysis, the relative risk of injury from drinking was 1.85 (p < .01) for those
      with an ED-treated injury, 1.42 (ns) for those with an other-treated injury, and
      1.43 (ns) for those with a nontreated injury. Alcohol-attributable fractions
      based on these relative risk estimates were 2.96% for an ED-treated injury, 1.59%
      for an other-treated injury, and 1.89% for a nontreated injury. Comparative
      attributable fractions based on the person's causal attribution of injury to his
      or her drinking were 3.06%, 1.61%, and 1.47%, respectively. Although these
      attributable fractions based on case-crossover analysis and subjective evaluation
      of causal attribution were not greatly different, all estimates were considerably
      smaller than those found in studies of ED patients. CONCLUSIONS: The data suggest
      that alcohol plays a larger role in those injuries for which treatment is sought
      in EDs, and this may be related to the severity of the injury. Additional studies
      of alcohol and injury in general populations that take into account the intensity
      of exposure to alcohol before the event, as well as recall bias by eliciting data
      on the proximity of the event to the time of the respondent interview, are
      necessary for determining unbiased estimates of the attributable fraction of
      alcohol in injury morbidity.

PMID- 18612567
TI  - The relationship between depressive symptom levels and subsequent increases in
      substance use among youth with severe emotional disturbance.
AB  - OBJECTIVE: This study examined the relationship between levels of depressive
      symptoms and subsequent increases in substance use among 784 youth with severe
      emotional disturbance enrolled in Medicaid-funded behavioral health care plans.
      METHOD: Youth at five sites nationwide were interviewed about their emotional and
      behavior problems, as well as their use of cigarettes, alcohol, and drugs--at
      both baseline and follow-up. RESULTS: (1) Levels of depressive symptoms were
      significantly associated with concurrent substance use at baseline. (2) Baseline
      levels of depressive symptoms predicted subsequent changes in substance use,
      especially use of illicit drugs and multiple drugs. (3) These findings remained
      significant, even after controlling for sociodemographic, family, and individual
      characteristics. CONCLUSIONS: These results indicate that depressive symptoms
      early in life may signal a risk for increasing involvement in substance use among
      severe emotional disturbed youth. This finding has important clinical
      implications for the prevention of substance misuse in this population.

PMID- 18612570
TI  - The consequences of providing drinkers with blood alcohol concentration
      information on assessments of alcohol impairment and drunk-driving risk.
AB  - OBJECTIVE: We examined the effect of providing drinkers with blood alcohol
      concentration (BAC) information on subjective assessments of alcohol impairment
      and drunk-driving risk. METHOD: We sampled 959 drinking participants from a
      natural drinking environment and asked them to self-administer a personal saliva
      based alcohol test. Participants then were asked to rate their alcohol impairment
      and to indicate whether they could drive legally under one of four BAC feedback
      conditions (assigned at random): (1) control condition (no BAC feedback provided
      before the ratings); (2) categorical BAC information (low, high, and highest
      risk) from the saliva test; (3) categorical BAC information corroborated by a
      calibrated police breath alcohol analyzer; and (4) precise (three-digit) BAC
      information from the breath alcohol analyzer. RESULTS: Both control participants
      and participants who received precise BAC feedback gave subjective impairment
      ratings that correlated with actual BACs. For participants who received
      categorical BAC information from the saliva test, subjective impairment did not
      correlate with the actual BAC. Providing drinkers with BAC information, however,
      did help them predict more accurately if their BAC was higher than the legal BAC
      driving limit. CONCLUSIONS: Although BAC information can influence drinkers'
      assessments of alcohol impairment and drunk-driving risk, there is no strong
      evidence that personal saliva-based alcohol tests are particularly useful.

PMID- 18612571
TI  - Brief alcohol intervention in the emergency department: moderators of
      effectiveness.
AB  - OBJECTIVE: Prior research supports the effectiveness of brief interventions for
      reducing alcohol misuse among patients in the emergency department (ED). However,
      limited information is available regarding the mechanisms of change, which could
      assist clinicians in streamlining or amplifying these interventions. This article
      examines moderators of outcomes among ED patients, ages 19 and older, who
      participated in a randomized controlled trial of a brief intervention for alcohol
      misuse. METHOD: Injured patients (N= 4,476) completed a computerized survey; 575
      at-risk drinkers were randomly assigned to one of four brief intervention
      conditions, and 85% were interviewed again at 3-month and 12-month follow-ups.
      RESULTS: Regression models using the generalized estimating equations approach
      examined interaction effects between intervention condition (advice/no advice)
      and hypothesized moderator variables (stage of change, self-efficacy, acute
      alcohol use, attribution of injury to alcohol) on alcohol outcomes over time.
      Overall, participants who reported higher levels of self-efficacy had lower
      weekly consumption and consequences, whereas those with higher readiness to
      change had greater weekly consumption and consequences. Furthermore, individuals
      who attributed their injury to alcohol and received advice had significantly
      lower levels of average weekly alcohol consumption and less frequent heavy
      drinking from baseline to 12-month follow-up compared with those who attributed
      their injury to alcohol but did not receive advice. CONCLUSIONS: This study
      provides novel data regarding attribution for alcohol-related injury as an
      important moderator of change and suggests that highlighting the alcohol/injury
      connection in brief, ED-based alcohol interventions can augment their
      effectiveness.

PMID- 18612572
TI  - Characteristics of individuals screening positive for substance use in a welfare
      setting: implications for welfare and substance-use disorders treatment systems.
AB  - OBJECTIVE: This study examined barriers to employability, motivation to abstain
      from substances and to work, and involvement in multiple service systems among
      male and female welfare applicants with alcohol- and drug-use problems. METHOD: A
      representative sample (N= 1,431) of all persons applying for public assistance
      who screened positive for substance involvement over a 2-year period in a large
      urban county were recruited in welfare offices. Legal, education, general health,
      mental health, employment, housing, and child welfare barriers to employability
      were assessed, as were readiness to abstain from substance use and readiness to
      work. RESULTS: Only 1 in 20 participants reported no barrier other than substance
      use, whereas 70% reported at least two other barriers and 40% reported three or
      more. Moreover, 70% of participants experienced at least one additional barrier
      classified as "severe" and 30% experienced two or more. The number and type of
      barriers differed by gender. Latent class analysis revealed four main barriers
      plus-readiness profiles among participants: (1) multiple barriers, (2) work
      experienced, (3) criminal justice, and (4) unstable housing. CONCLUSIONS:
      Findings suggest that comprehensive coordination among social service systems is
      needed to address the complex problems of low-income Americans with substance-use
      disorders. Classifying applicants based on barriers and readiness is a promising
      approach to developing innovative welfare programs to serve the diverse needs of
      men and women with substance-related problems.

PMID- 18612573
TI  - Testing the level of response to alcohol-based model of heavy drinking and
      alcohol problems in offspring from the San Diego Prospective Study.
AB  - OBJECTIVE: The low level of response (LR) to alcohol, an endophenotype related to
      heavy drinking and alcohol problems, influences the risk for alcoholism in the
      context of additional life domains. This article evaluates an LR-based model of
      drinking patterns in 113 drinking offspring, ages 12 to 24 years, from the San
      Diego Prospective Study. METHOD: Correlations and structural equation models
      (SEMs) were evaluated using LR as measured from the Self-Report of the Effects of
      Alcohol questionnaire in the offspring. The expectations of the effects of
      alcohol (EXPECT), the perception of drinking in peers (PEER), the use of alcohol
      to cope with stress (COPE), and the drinking quantities and alcohol-related
      problems (ALCOUT) were evaluated in the SEM. RESULTS: The LR-based model worked
      well, with good fit characteristics and 78% of the variance of outcome explained.
      LR related directly to ALCOUT, with additional mediation of that relationship
      through EXPECT and COPE. CONCLUSIONS: The LR-based model performed well in
      adolescents from the San Diego Prospective Study. Knowledge of which domains
      mediate how LR impacts alcohol-related outcomes may be useful in developing more
      focused and potentially more effective prevention approaches.

PMID- 18612574
TI  - Interactive voice response versus computer-assisted telephone interviewing (CATI)
      surveys and sensitive questions: the 2005 National Alcohol Survey.
AB  - OBJECTIVE: Interactive voice response (IVR), a computer-based interviewing
      technique in which respondents interact directly with a computerized system, can
      increase a sense of privacy and potentially a willingness to report putatively
      sensitive attitudes and behaviors more accurately. The purpose of this study was
      to compare the prevalence rates obtained by IVR with computer-assisted telephone
      interviewing (CATI) for alcohol-related problems, physical and sexual abuse, and
      sexual orientation. METHOD: As part of the data collection effort for the 2005
      National Alcohol Survey, subsamples of respondents were randomly assigned to
      three groups: two IVR groups, each receiving an IVR module on either alcohol
      related problems (n = 562) or on physical/sexual abuse and sexual orientation (n
      = 563), and control groups that did not receive IVR (n = 559). RESULTS: Analyses
      indicate no significant differences between IVR and the control groups on alcohol
      related problems. A significantly higher proportion of reports of homosexual and
      bisexual sexual identity was found in the IVR group for respondents 40 years and
      older. The IVR group also reported higher rates of condom use for respondents 18
      39 years old. CONCLUSIONS: These findings suggest that alcohol-related problems
      may no longer be considered sensitive items in the general adult population.
      However, reports of nonheterosexual sexual orientation identity remain sensitive
      for older respondents. Embedding IVR within a telephone interview may provide an
      effective way of helping assure valid responses to sensitive item content.

PMID- 18612575
TI  - Five-year outcomes of alcohol-dependent persons treated with motivational
      enhancement.
AB  - OBJECTIVE: The purpose of this study was to determine whether the superior
      treatment effect of motivational enhancement therapy (MET) previously
      demonstrated at 6 months was sustained at a 5-year posttreatment follow-up.
      METHOD: Patients with mild to moderate alcohol dependence had completed a trial
      in which all patients were assessed, attended a brief feedback session, and were
      randomized to four sessions of MET, nondirective reflective listening, or no
      further counseling. The primary drinking outcome was unequivocal heavy drinking
      (UHD), defined as drinking 10 or more standard drinks on six or more occasions
      over a 6-month period. At the 6-month follow-up, 108 of 122 patients agreed to a
      further follow-up interview. RESULTS: Seventy-seven patients were successfully
      followed for a mean (SD) of 58 (14) months after the completion of treatment.
      Although the group as a whole had continued to improve, with rates of UHD reduced
      from 51 % at 6 months to 25% at 5 years, there was no difference by treatment
      group in drinking for UHD or a range of lower drinking thresholds. CONCLUSIONS:
      Although 5-year outcomes were indistinguishable among the three treatment groups,
      this was the result of patients in the comparison conditions catching up to the
      drinking gains of MET patients rather than a deterioration in drinking for MET
      patients. Individuals allocated to receive MET achieved a greater reduction
      sooner than either of the comparison treatment conditions.

PMID- 18612577
TI  - Accuracy of photographs to capture respondent-defined drink size.
AB  - OBJECTIVE: Evidence suggests that people misjudge the size of their drinks,
      calling into question the validity of data from surveys and screening instruments
      assessing alcohol quantity in terms of standard drinks. This article studied the
      validity of photographs of glasses to assess drink size. METHOD: In a U.S.
      national sample of 323 drinkers, respondents were mailed a measuring beaker and a
      set of photographs of wine, beer, and other drinking glasses for use in a
      subsequent telephone survey. In the interview, they were asked to pick the glass
      most similar to what they use at home and to identify the letter associated with
      their usual pour level. Then, a protocol where subjects measured the actual
      number of ounces in their typical drink, by pouring water into their usual glass
      and measuring this volume using the measuring beaker, gave a direct measure of
      home drink volume. We compared drink sizes using the two approaches. RESULTS:
      Photographs worked well for certain groups, including women, young people, and
      nonwhites (for wine) and whites (for beer). The greatest magnitude of error
      arising from the use of photographs was for wine drinks among those age 50 and
      older, those with a 4-year degree, frequent 5+ drinkers in general, and heavy
      volume wine drinkers. Average drink size based on the most popular wine and beer
      glasses in the photographs were 0.62 oz (18 ml) and 1.62 oz (48 ml) larger than
      beaker pours, respectively. Error between actual drinks and photographs was
      especially high for a large balloon-shaped wine glass, chosen by only 3% of wine
      drinkers. CONCLUSIONS: Whenever possible, researchers and clinicians should
      incorporate protocols that allow for some type of direct measurement using the
      actual vessels from home. When this is not viable, photographs represent a
      solution that is practical, shows promise for beer and wine drinks, and is
      relevant to any drinking context.

PMID- 18612576
TI  - Lapses following alcohol treatment: modeling the falls from the wagon.
AB  - OBJECTIVE: This study investigated transitions between drinking and nondrinking
      during the first 12 months following treatment and whether transitions in
      posttreatment drinking are related to alcohol-dependence symptoms. METHOD: Data
      from individuals in the outpatient (n = 952) and aftercare (n = 774) arms of
      Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) were
      included in the analyses. Drinking consequences, percentage of drinking days, and
      drinks per drinking day were used as indicators of drinking behavior. Latent
      transition analysis was used to estimate a model of drinking patterns, defined by
      transition probabilities between drinking classes, from immediately following
      treatment to 6 and 12 months following treatment. RESULTS: Across both aftercare
      and outpatient samples, three drinking classes were identified at each time
      point: frequent heavy drinking with high consequences, moderate infrequent
      drinking with low consequences, and nondrinking with low consequences. Many
      participants maintained nondrinking, and, of those who drank, there was a trend
      toward transitioning to less drinking over time. Transition probabilities were
      noninvariant across treatment arms: The probability of transitioning from
      moderate drinking to frequent drinking was more than six times more likely in the
      aftercare arm, as compared with the outpatient arm. In both samples the
      transition to heavy drinking and membership in the heavy-drinking class were
      significantly positively related to alcohol dependence symptoms. There were no
      differences across MATCH treatment groups. CONCLUSIONS: This study examined
      transitions in post treatment drinking and the role of alcohol dependence in
      predicting posttreatment drinking. The results suggest a low probability of
      moderate drinking among individuals with greater alcohol dependence.

PMID- 18612578
TI  - Validation of the 30-day version of the Brief Young Adult Alcohol Consequences
      Questionnaire for use in longitudinal studies.
AB  - OBJECTIVE: The Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ) was
      developed using item response modeling to provide a brief and readily
      interpretable measure of negative alcohol consequences over the past year among
      college students. The purpose of the present study was to extend evaluation of
      the B-YAACQ by examining its psychometric properties when administered to college
      students cited for a university alcohol violation using a past 30-day time frame
      of assessment. METHOD: The B-YAACQ was administered at baseline and at a 6-week
      follow-up to 291 students cited for a university alcohol violation. Reliability
      and validity analyses, in addition to Rasch model analyses, were conducted using
      these data. RESULTS: Results demonstrated that the B-YAACQ was internally
      consistent, showed strong unidimensionality and additive properties, displayed
      minimal item redundancy and minimal floor or ceiling effects, was reliable over a
      6-week period, and was sensitive to change in drinking following an alcohol
      intervention. In addition, the relative severity of items was preserved over time
      and generally consistent with results from an earlier study. CONCLUSIONS: The 30
      day B-YAACQ seems valid for use with college students who have received an
      alcohol violation and for use in evaluating changes in alcohol consequences.

PMID- 18612579
TI  - Factor structure of the Alcohol Use Disorders Identification Test (AUDIT) for men
      and women in different age groups.
AB  - OBJECTIVE: Our main aim was to investigate the factor structure of the Alcohol
      Use Disorders Identification Test (AUDIT) in a Finnish population sample. METHOD:
      The AUDIT was completed by 3,125 men (mean age = 26.2 years) and 6,006 women
      (mean age = 26.1 years). RESULTS: At a cutoff score of 8 or more, 49.8% of the
      men and 23.9% of the women would be identified as potentially engaged in
      excessive alcohol use. Exploratory factor analyses suggested a two-factor
      solution for both men and women. However, the factor structure was not invariant
      between men and women or in the different age groups among men. CONCLUSIONS: This
      is one of the largest known general population studies on alcohol use in recent
      years in Finland. The findings support a two-factor solution, and it is suggested
      that the AUDIT cutoff scores should be tailored according to age, gender, and
      drinking culture.

PMID- 18612580
TI  - Relationship of calcification of atherosclerotic plaque and arterial stiffness to
      bone mineral density and osteoprotegerin in postmenopausal women referred for
      osteoporosis screening.
AB  - Arterial calcification leading to increased arterial stiffness, a powerful risk
      factor for cardiovascular disease, may underlie the association of osteoporosis
      with cardiovascular disease in postmenopausal women. Osteoprotegerin (OPG), an
      indirect inhibitor of osteoclastogenesis, may be involved in arterial
      calcification. We examined relationships between calcification of subclinical
      atherosclerotic plaque and arterial stiffness with bone mineral density (BMD) and
      OPG in a group of 54 postmenopausal women referred for routine osteoporosis
      screening by dual-energy X-ray absorptiometric scanning of the lumbar spine and
      hip. Presence of calcified and noncalcified plaque in carotid and femoral
      arteries was examined using ultrasonography. Pulse wave velocity (PWV), a measure
      of arterial stiffness, was determined by sequential tonometry over the carotid
      and femoral region. Fifty-nine percent of osteoporotic women had calcified
      (echogenic) plaque at one or more sites compared with 42% and 20% for women with
      osteopenia and normal BMD, respectively (P = 0.04). There was a significant
      negative correlation between PWV and hip BMD (r = -0.35, P = 0.01), which
      remained significant when age, mean arterial pressure, and serum lipids were
      taken into account (P = 0.05). No significant relationships were observed between
      serum concentrations of OPG and lumbar spine or total hip BMD or with the number
      of arterial sites with calcified or noncalcified plaque. However, there was a
      strong correlation between OPG and PWV (r = 0.44, P = 0.001), which remained
      significant when adjusted for age (P = 0.01). These findings suggest that
      decreased BMD is associated with arterial calcification and stiffening and raise
      the possibility that OPG is a marker of arterial stiffening, independent of any
      association with BMD.

PMID- 18612582
TI  - Bilateral variation of the pectoralis minor muscle discovered during practical
      dissection.
AB  - We describe a case of an original insertion of the pectoralis minor on the
      coracohumeral ligament, supraspinatus tendon and the capsule of the glenohumeral
      joint. This variation has been described in anatomy textbooks since the
      nineteenth century. The peculiarity of this case is that the right shoulder
      presented type 2 and the left type 1 of the three varieties described by Le
      Double in 1897. Le Double (1843-1913) was a French anatomist who wrote a treaty
      on anatomical variations, in particular those of the muscle. Lately, only three
      publications have reported this variation in anatomic studies. Some authors have
      described the rotator cuff syndrome caused by this variation and an ultrasound
      study has demonstrated a frequency of 9.57% for the detection of this variation.
      It is possible to try and find this variation while investigating in order to
      diagnose impingement, through ultrasound, CT arthrography or MRI. We believe that
      this variation should be taken into consideration by surgeons during surgical
      procedures and arthroscopy.

PMID- 18612583
TI  - Role of deltoid and passives elements in stabilization during abduction motion (0
      degrees-40 degrees): an ex vivo study.
AB  - The deltoid and the passive elements of the glenohumeral joint play a role during
      abduction of the upper limb. However, there is a lack of quantification of their
      respective role. The aim of the present study was to describe the influence of
      the deltoid and the passive elements during kinematics experiments in abduction
      (0 degrees-40 degrees) of unconstrained humerus. Six fresh-frozen anatomical
      specimens were considered. Bi-planar X-rays were obtained using the EOS imaging
      system (Biospace Med, Paris, France). Then a horizontal traction at constant
      speed was applied to the "acromion and clavicle block", using an universal
      testing machine and specific device, and the humerus kinematics was recorded
      using an optoelectronic system (Polaris, NDI, Canada). For each anatomical
      specimen the protocol included two types of tests: intact capsule and perforated
      capsule. For a displacement of 28 mm of the acromio-clavicular set, the
      amplitudes of "abduction" rotation vary between 26 degrees and 41 degrees for the
      "intact capsule" configuration and between 27 degrees and 40.5 degrees for
      injured capsule configuration. For the same displacement the translation
      according to Y of the humeral head changes between 1 and 5.5 mm for intact
      capsule configuration and between -0.5 and 5.5 mm for injured capsule
      configuration. During the abduction (0 degrees-40 degrees) motion this study
      suggests that the humeral head is stabilized by the deltoid, the labrum, tendons
      of the rotators cuff and to a lesser level by the glenoid.

PMID- 18612584
TI  - Exercise just before glucose ingestion does not deteriorate glucose tolerance in
      well controlled patients with type 2 diabetes mellitus who exercise regularly.

PMID- 18612585
TI  - Schwannomas of the upper extremity: diagnosis and treatment.
AB  - Schwannomas are the most common benign tumors developing in peripheral nerves.
      They account for 5% of all tumors in upper extremity. They usually present as a
      slow-growing mass, sometimes associated to pain and paresthesia. Preoperative
      evaluation is based on US and MRI, but final diagnosis requires histopathology.
      The aim of this study is to define clinical findings and MRI characteristics in
      identification, localization, and possible differential diagnosis of schwannomas.

PMID- 18612586
TI  - Lack of vertical transmission of Hantaan virus from persistently infected dam to
      progeny in laboratory mice.
AB  - It is unclear how the hantaviruses are transferred from infected to uninfected
      rodents. We studied the status of persistently infected laboratory mice and
      examined the frequency of viral transmission to their offspring. Expression of
      Hantaan virus nucleocapsid protein was detected in the lungs of persistently
      infected dams. None of the progeny displayed viral antigen, although they were
      strongly positive for IgG antibodies against hantavirus. There was neither
      hantavirus RNA nor virus-specific IgM antibodies or virus-specific CD8(+) T cells
      in the progeny. These results did not show any indication for a vertical
      transmission of hantaviruses, at least in the laboratory mouse model studied.

PMID- 18612587
TI  - The origins of replication of granuloviruses.
AB  - The genomes of eight granuloviruses (GVs), have been analyzed for the presence of
      homologous regions (hrs) that may act as origins of replication. Thirteen 74-76
      bp palindromes within 11 hrs have previously been identified in the Cydia
      pomonella GV (CpGV) genome and found to replicate in an infection-dependent DNA
      replication assay. We report a further palindrome within one of the hrs, which
      was found to replicate, bringing the total to 14 palindromes. We also report
      imperfect palindromes, with similar 13-bp end sequences to the CpGV palindromes,
      within the Adoxophyes orana GV, Cryptophlebia leucotreta GV (CrleGV),
      Choristoneura occidentalis GV and Phthorimaea operculella GV genomes. No hrs were
      detected in Agrotis segetum GV, and no additional hrs or palindromes, other than
      those published, were detected in the Plutella xylostella GV and Xestia c-nigrum
      GV genomes. Several putative hrs from the GVs were tested for replication in C.
      pomonella cells using a CpGV-dependent replication assay. Two CrleGV hrs were
      found to replicate at a low level.

PMID- 18612588
TI  - RET polymorphisms and the risk of Hirschsprung's disease in a Chinese population.
AB  - Hirschsprung's disease (HSCR) is a congenital disorder characterized by
      intestinal obstructions due to the absence of enteric ganglia along variable
      lengths of the intestinal tract. RET coding mutations have been found in
      approximately 50% of familial cases, but they only explain a minority of sporadic
      cases. Here, we report our investigation of a possible role of RET non-coding
      mutations in sporadic HSCR patients. The haplotypes of seven single nucleotide
      polymorphisms (SNPs), all located in a region 4 kb upstream of the gene through
      to 23 kb of intron 1, and one SNP in exon 2 were constructed in 125 Han Chinese
      patients with sporadic HSCR and in 148 Han Chinese controls. Our results
      indicated that eight SNPs were significantly associated with HSCR (P < 0.0001).
      The C allele of rs2505535 would appear to represent a protecting allele for the
      Chinese population. One single haplotype composed of these eight markers was
      present in 59.6% of patients, versus 18.1% of controls. Based on our results, we
      conclude that non-coding mutations in RET have important roles in the development
      of HSCR. The unknown functional disease variant(s), with a dosage-dependent
      effect in HSCR, is likely to be located in the 5'-region of the RET gene.

PMID- 18612589
TI  - Vesicoureteral reflux: genetic associations besides the Hinman syndrome.

PMID- 18612590
TI  - N-benzoxazol-2-yl-N'-1-(isoquinolin-3-yl-ethylidene)-hydrazine, a novel compound
      with antitumor activity, induces radicals and dissipation of mitochondrial
      membrane potential.
AB  - The novel compound N-benzoxazol-2-yl-N'-1-(isoquinolin-3-yl-ethylidene)-hydrazine
      (EPH136) has been shown to exhibit antitumor activity in vitro and in vivo. A
      COMPARE analysis showed that the patterns of cellular effects of EPH136 are not
      related to any of 175 standard antitumor agents with a known mechanism of action.
      In order to help identify the mechanism of action we employed a bioinformatics
      approach called partial least squares modelling in latent variables in which the
      expression levels of approximately 8,000 genes in each of 56 untreated NCI panel
      cell lines were correlated with the respective IC(50) values of each cell line
      following treatment with EPH136. The 60 genes found to be most important for the
      antiproliferative effect of EPH136 are involved in nucleoside, nucleotide,
      nucleic acid binding and metabolism, developmental processes, protein
      modification and metabolism. In addition, using a DNA microarray we measured the
      expression of approximately 5,000 known genes following treatment of HT-29 colon
      carcinoma cells with a two-fold IC(50) concentration of EPH136. The genes that
      were up-regulated more than two-fold compared to untreated controls belong to the
      same classes as found by the bioinformatic approach. Many of these proteins are
      regulated by oxidation/reduction and so we concluded that formation of radicals
      may be involved in the mechanism of action. We show here that EPH136 leads to
      generation of oxygen radicals, swelling of mitochondria and dissipation of the
      mitochondrial membrane potential. The antiproliferative activity of EPH136 was
      prevented by the radical scavenger N-acetylcysteine. Cells with elevated
      glutathione exhibited resistance to EPH136. In summary, the mechanism of the
      novel experimental anticancer drug EPH136 is generation of radicals and
      dissipation of the mitochondrial membrane potential.

PMID- 18612591
TI  - Trastuzumab induces gastrointestinal side effects in HER2-overexpressing breast
      cancer patients.
AB  - PURPOSE: To characterise the gastrointestinal toxicities associated with
      Trastuzumab administration in HER2-overexpressing breast cancer patients.
      METHODS: All patients (n = 46) who received Trastuzumab as a single agent or in
      conjunction with conventional anti-cancer treatment within the Royal Adelaide
      Hospital Cancer Centre from 2002-2007 were included in this study. A
      retrospective analysis of case-notes was conducted to investigate the toxicities
      associated with Trastuzumab. RESULTS: Trastuzumab as a single agent induced
      toxicities following 22% of administrations. Gastrointestinal toxicities were
      observed following 12% of administrations and included nausea and vomiting,
      diarrhoea, abdominal pain and bloating. However, other prominent toxicities that
      were not related to the gastrointestinal tract were also observed including
      fatigue and lung symptoms (10.4%). Elderly patients (> or =60 years) and those
      with metastatic disease experienced the highest frequency of toxicity.
      CONCLUSION: Trastuzumab induces a range of gastrointestinal toxicities in HER2
      overexpressing breast cancer patients. These toxicities are separate to those
      caused by concurrent chemotherapy and/or radiotherapy.

PMID- 18612592
TI  - Use of soybean protein hydrolysates for promoting proliferation of human
      keratinocytes in serum-free medium.
AB  - Human keratinocytes are generally cultured in media containing bovine pituitary
      extract (BPE), an animal product that can be a source of infectious contaminants.
      We investigated whether a safer plant product could replace BPE in the culture
      medium. Medium containing both BPE and soy protein hydrolysates (Bacto Soytone
      and Soy Hydrolysate) produced the largest number of viable cells, followed in
      descending order by medium supplemented only with BPE, only with the
      hydrolysates, and without supplementation (basal medium only). Soybean protein is
      thus an excellent source of nutrients for the growth of adherent keratinocytes,
      although they do not fully substitute for BPE.

PMID- 18612593
TI  - Polyglycolic acid filaments guide Schwann cell migration in vitro and in vivo.
AB  - Nerve conduits filled with longitudinal aligned filaments have demonstrated a
      better regenerative outcome for bridging large peripheral nerve gaps than hollow
      nerve conduits. In the present study, we investigated the in vitro and in vitro
      cellular behavior of Schwann cells on polyglycolic acid (PGA) filaments by
      immunocyto/histochemistry and light/electron microscopy. After 1-3-week culture
      of rat dorsal root ganglia (DRGs) onto PGA filaments, Schwann cells from rat DRGs
      adhered to and migrated along PGA filaments. Twenty-four rats received
      implantation of chitosan conduits inserted with PGA filaments to bridge 10-mm
      long sciatic nerve gaps. At 1, 2, 3 and 4 weeks post-implantation (n = 6, each
      time point), Schwann cells were found to migrate along PGA filaments and form
      cell columns resembling bands of Bungner. These results suggest that PGA
      filaments may play a contact guidance role in Schwann cell migration and thus
      serve as a promising conduit-filling material to facilitate peripheral nerve
      repair.

PMID- 18612594
TI  - Isolation and characterization of bamA genes, homologues of the gamma
      butyrolactone autoregulator-receptor gene in Amycolatopsis mediterranei, a
      rifamycin producer.
AB  - Four genes (bamA1, bamA2, bamA3 and bamA4) encoding homologues of the gamma
      butyrolactone autoregulator receptor of Streptomyces were found and cloned from
      Amycolatopsis mediterranei, a typical non-Streptomyces actinomycetes and a
      producer of rifamycin, one of the major anti-tuberculosis drugs in clinical
      treatment. Transcriptional analysis demonstrated that bamA1 and bamA2 are
      transcribed in a growth-dependent manner, while bamA3 and bamA4 are
      constitutively transcribed during growth. Binding assays using (3)H-labeled
      autoregulator analogues as ligands confirmed that all of the recombinant BamA
      proteins expressed in Escherichia coli have clear binding activity toward several
      types of Streptomyces autoregulators. The ligand specificity of the recombinant
      BamA1 protein was identical to that of the crude cell-free lysates of A.
      mediterranei reported in our previous work. These results suggest that A.
      mediterranei, which is phylogenetically situated in a distal clade from the genus
      Streptomyces as non-Streptomyces actinomycetes, has an autoregulator-mediated
      signaling system.

PMID- 18612595
TI  - Microbial production of fructosyltransferases for synthesis of pre-biotics.
AB  - Fructooligosaccharides (FOS) are prebiotic substances found in several vegetable
      or natural foods. The main commercial production of FOS comes from enzymatic
      transformation of sucrose by the microbial enzyme fructosyltransferase. The
      development of more efficient enzymes, with high activity and stability, is
      required and this has attracted the interest of biotechnologists and
      microbiologists with production by several microorganisms being studied. This
      article reviews and discusses FOS chemical structure, enzyme characteristics, the
      nomenclature, producer microorganisms and enzyme production both in solid state
      fermentation and submerged cultivation.

PMID- 18612596
TI  - Cathodic reduction of hexavalent chromium [Cr(VI)] coupled with electricity
      generation in microbial fuel cells.
AB  - A novel approach to Cr(VI)-contaminated wastewater treatment was investigated
      using microbial fuel cell technologies in fed-batch mode. By using synthetic
      Cr(VI)-containing wastewater as catholyte and anaerobic microorganisms as anodic
      biocatalyst, Cr(VI) at 100 mg/l was completely removed during 150 h (initial pH
      2). The maximum power density of 150 mW/m(2) (0.04 mA/cm(2)) and the maximum open
      circuit voltage of 0.91 V were generated with Cr(VI) at 200 mg/l as electron
      acceptor. This work verifies the possibility of simultaneous electricity
      production and cathodic Cr(VI) reduction.

PMID- 18612597
TI  - Dioxygenase- and monooxygenase-catalysed synthesis of cis-dihydrodiols,
      catechols, epoxides and other oxygenated products.
AB  - Oxidoreductases are an emerging class of biotechnologically relevant enzymes due
      to their regio- and stereo-specificity. The selective oxygenation of aromatic
      compounds by oxidoreductases has received much attention and a wide range of
      reactions have been documented using these enzymes from various microbial
      sources. This review gives an overview of various dioxygenase, monooxygenase and
      oxidase enzymes that have been manipulated for the synthesis of products such as
      cis-dihydrodiols, catechols, epoxides and other oxygenated products. The use of
      protein engineering and its advancement in the synthesis of recombinant enzymes
      is also discussed.

PMID- 18612598
TI  - Serine hydroxamate and the transcriptome of high cell density recombinant
      Escherichia coli MG1655.
AB  - For more than 30 years, serine hydroxamate has been used to chemically stimulate
      a stringent response in Escherichia coli and other bacteria. These studies have
      elucidated numerous characteristics of the classical stringent response beyond
      the simple cellular response to an amino acid shortage, including phospholipid
      synthesis and protease upregulation. In this study, the effects of a serine
      hydroxamate addition on high-cell-density recombinant E. coli were examined and
      compared to the effects of recombinant protein production to determine overlaps,
      as recombinant protein production stress has often been attributed to amino acid
      shortages. Both the transcriptome and growth characteristics were evaluated and
      compared. The serine hydroxamate addition profoundly decreased the culture growth
      rate, whereas recombinant protein production did not. Conversely, the
      transcriptome profile of the recombinant E. coli cultures were relatively
      unaffected by the serine hydroxamate addition, yet recombinant protein production
      dramatically changed the transcriptome profile. A subset of the classical
      stringent response genes were effected by the serine hydroxamate addition,
      whereas recombinant protein production regulated numerous classical stringent
      response genes but not all. The genes that were regulated by the serine
      hydroxamate addition include numerous fatty acid synthesis genes, in agreement
      with altered phospholipids synthesis reports. These results indicate that
      recombinant protein production and the stringent response have many overlapping
      responses but are far from identical.

PMID- 18612600
TI  - Understanding of the molecular mechanisms of allergy.
AB  - The prevalence of allergic disease has dramatically increased over the past 30
      years in Westernised countries. It is unlikely that the rapid increase in the
      prevalence of allergic disease is the result of genetic changes, which highlights
      the importance of environmental factors in the development of allergic disease.
      The 'hygiene hypothesis' was put forward in 1989 and focused attention on the
      notion that exposure to microbes and their products in early life can modify the
      risk for development of allergic disease. Infections were thought to polarize the
      immunological response towards a Th2-mediated immune responses causing allergic
      disease. However it is likely that the Th1/Th2 imbalance is too simplistic to
      explain the increased prevalence of allergic disease. Current research is
      focusing on understanding the role of T regulatory cells in inducing a state of
      tolerance and the resulting modified Th2 response observed in natural and induced
      tolerance.

PMID- 18612599
TI  - Adaptation of glucokinase gene expression in the rat dorsal vagal complex in a
      model for recurrent intermediate insulin-induced hypoglycemia: impact of gender.
AB  - Standard therapeutic management of insulin-dependent diabetes mellitus with
      intermediate-acting insulin poses a significant risk for iatrogenic hypoglycemia
      and associated hypoglycemia-associated autonomic failure. Gender differences in
      preservation of counterregulatory function during recurring hypoglycemia have
      been documented in the clinical setting. In rats, repeated induction of prolonged
      hypoglycemia by neutral protamine Hagadorn insulin (NPH) results in diminished
      neuronal transcriptional activation in several key metabolic loci in male, but
      not female rat brain, including the hindbrain dorsal vagal complex (DVC). Glucose
      is committed to glycolytic catabolism by hexokinase-mediated phosphorylation. The
      low-affinity, high K (m) hexokinase, glucokinase (GCK), monitors intracellular
      glucose levels in pancreatic beta cells, and is purported to fulfill a similar
      function in the CNS. GCK is expressed in the rat DVC, where mRNA is localized to
      neurons that exhibit electrophysiological sensitivity to glucose imbalance. The
      current study investigated the hypothesis that DVC GCK gene expression acclimates
      to RIIH in a gender-dependent manner. Quantitative real-time RT-PCR was used to
      evaluate GCK mRNA levels in microdissected DVC tissue obtained from male and
      female rats before or after one or serial doses of NPH. Basal DVC GCK transcripts
      were equal between ovariectomized (OVX) female rats implanted with estradiol
      benzoate (EB) or oil (O). Tissue mRNA levels were increased following a single
      NPH injection in both groups, but this response was greater in the presence of
      estrogen. Basal GCK gene expression was elevated by precedent insulin dosing in
      both O- and EB-implanted rats; however, transcripts were not modified relative to
      this adjusted baseline during subsequent NPH treatment in either group of
      females. While acute NPH treatment did not modify tissue transcript levels in
      orchidectomized (ORDX) or sham-ORDX rats, precedent NPH dosing increased basal
      GCK mRNA levels and further enhanced gene expression during ensuring hypoglycemia
      in sham males. These studies provide novel evidence for gender-dimorphic DVC GCK
      gene responses to single and serial intermediate-acting insulin administration.
      Further research is required to determine if and how stimulatory versus
      inhibitory transcriptional adaptation of this gene profile in male and female
      rats, respectively, impacts glucose-sensing functions in the DVC, and whether
      such adjustments may contribute to gender differences in magnitude of precedent
      hypoglycemic impairment of counterregulation.

PMID- 18612601
TI  - T cell - primary culture from peripheral blood.
AB  - Peripheral blood mononuclear cells (PBMC) can be used to assess cell-mediated
      immunity in general or, via antigen-specific stimulation, to detect previous
      exposure to a variety of antigens/allergens and to monitor the response to
      immunotherapies. Peripheral blood is the most common source of mononuclear cells
      for in vitro cultures, although mononuclear cells can be obtained from other
      sources involved in the allergic reaction. PBMC from individuals previously
      exposed to an antigen proliferate in vitro when stimulated with the specific
      antigen. Proliferation is measured by the incorporation of ((3)H)-thymidine into
      newly synthesized DNA. This parameter is often used as an end point of lymphocyte
      stimulation induced by antigen or antigen fragments (e.g., synthetic peptides),
      mitogens, or anti-CD3/anti-CD28 combinations. The aim of this chapter is to
      describe the culture of T cells obtained from peripheral blood and the collection
      of cell supernatants for cytokine measurement.

PMID- 18612602
TI  - Production of T-cell lines.
AB  - Allergen-specific T-cell lines established from allergic patients provide the
      opportunity of investigating T-cell functions at the poly- or oligoclonal level.
      T-cell lines are useful in determining the presence or absence of antigen
      specific T-cell reactivity. However, to obtain detailed knowledge of the action
      of T cells with clearly defined features, for example epitope specificity or
      phenotype, T-cell clones are necessary.The frequency of allergen-specific T cells
      in peripheral blood mononuclear cells (PBMC) tends to be low and so stimulation
      of PBMC with single allergens often results in low allergen-specific reactivity
      or requires high doses of the allergen. In contrast, the stimulation of PBMC with
      whole allergen extract results in stronger reactivity because a greater spectrum
      of T-cell specificities is addressed. Therefore, for the investigation of
      polyclonal reactivity toward single allergens it is useful to establish T-cell
      lines, which represent an allergen-specific enrichment of T cells from the
      respective individual. These T cells are poly- or oligoclonal and might possess
      different epitope specificities. The method described here is based on
      experiences with human T-cell lines and clones specific for several allergens
      from grass pollens and tree pollens.

PMID- 18612603
TI  - Ultrasensitive ELISA for measurement of human cytokine responses in primary
      culture.
AB  - ELISAs offer excellent specificity and, once fully optimized, sensitivity that
      rivals that of bioassays. The major variables that need to be experimentally
      determined when developing an ELISA are the optimal number of fresh cells
      required per well, the optimal antigen concentrations for stimulation, period of
      culture, and the anticipated intensity of the response. In this chapter, we
      review the major factors to be considered in the development and application of
      ultrasensitive ELISAs to the analysis of human immune responses. We specify the
      conditions we have found to be optimal for quantifying a number of cytokines of
      demonstrated relevance to human immune regulation and discuss the major pitfalls
      inherent in this approach.

PMID- 18612604
TI  - Quantification of human chemokine production in TLR-stimulated and antigen
      specific recall responses.
AB  - Chemokines are primarily low molecular mass proteins that are produced and
      usually released by a wide variety of cell types. Differential chemokine
      responses can be excellent early markers of immune dysfunction, allowing clinical
      intervention prior to expression of full blown undesirable effector responses.
      Thus, assessment of the nature and intensity of Ag-dependent chemokine production
      provides a valuable tool for probing human immune regulation.Here, we provide
      detailed instructions on approaches we have developed to assess the nature and
      intensity of recall responses to a wide variety of exogenous and endogenous
      antigens capable of consistently stimulating chemokine responses by PBMC from
      adult and pediatric populations. This chapter is divided into two sections. The
      first is focused on culture techniques for eliciting antigen-driven chemokine
      responses for a panel of chemokines that are relevant to immune function. The
      second section details assay systems for their quantitative analysis.

PMID- 18612605
TI  - Standardization of allergen extracts.
AB  - Allergens are molecules with the capacity to elicit IgE responses in humans. When
      stimulated with allergens, most allergic patients respond with production of IgE
      specific for several proteins/allergens in the source material. The
      standardization of allergen extracts is essential in order to control variability
      and to achieve consistency and reproducibility in a clinical setting. Because the
      IgE binding capacity of an allergen extract is related to the content of one or a
      few major allergens, it is important that the standardization procedure ensures
      consistency, not only in the overall IgE binding potency, but also in the content
      and ratio of individual major allergens. Owing to the complexity of allergen
      extracts, a key element in standardization of allergen extracts is the use of
      standards. This chapter describes the principles for standardization of allergen
      extracts to be used by research laboratories. Other chapters in this volume
      describe methods in detail.

PMID- 18612606
TI  - Immunoelectrophoresis for the characterization of allergen extracts.
AB  - Immunoelectrophoresis can be used for analysis of individual proteins in complex
      mixtures. The conditions involved in immunoelectrophoresis are mild, avoiding the
      risk of denaturation, and it is possible to perform relative quantification of
      individual components. The principle disadvantage is the dependence on rabbit
      antisera as reagents. The usefulness of immunoelectrophoresis in allergy research
      is greatly enhanced by the possibility of identification of allergens to which
      the individual in question has IgE. The common principle is characterized by two
      independent electrophoreses having direction of current perpendicular to each
      other, i.e., crossed immunoelectrophoresis (CIE). This ultimately results in the
      formation of characteristic bell-shaped precipitates, each precipitate
      representing one antigen. There is a linear relationship between the amount of
      antigen and size of precipitate for a given antibody concentration for each
      precipitate and so relative quantification can be performed. The sensitivity and
      resolution power of CIE is very high and there are multiple variations of the
      technique, some of which will be illustrated in this chapter.

PMID- 18612607
TI  - Conjugation of haptens.
AB  - Many naturally occurring proteins, peptides, carbohydrates, nucleic acids, and
      lipids, as well as synthetic peptides, are successful immunogens. To elicit an
      immune response, a compound must contain an antigenic determinant or epitope and
      must be of sufficient size to initiate lymphocyte activation necessary for an
      antibody response. In practice, small chemical compounds (haptens) are generally
      not good immunogens. However, when attached to macromolecules (carriers), they
      can become immunogenic. An immunogen must have epitopes that can be recognized by
      antigen-presenting cells and a T-cell receptor, and it must be degradable.
      Haptens and corresponding hapten-carrier conjugates have been essential to the
      development of sensitive quantitative and qualitative immunoassays. In the design
      of hapten conjugates, consideration must be given to the hapten, the carrier, the
      coupling strategy, and the hapten density because the amount of hapten attached
      to the carrier influences the strength of the immune response directed toward the
      newly created antigenic determinant. Hence the haptenic density of the conjugate
      is also important in the development of immunoassays. The optimal epitope density
      of a conjugate to elicit either a strong immune response or provide the best
      immunoassay is dependent on the structure of the epitope and the nature of the
      immunoassay. The aim of this chapter is to describe the diverse techniques used
      to couple haptens to carriers and provide guidance in the selection of the most
      appropriate procedure for a particular hapten.

PMID- 18612608
TI  - Monoclonal antibodies.
AB  - Monoclonal antibodies (mabs) are powerful tools for the quantification,
      detection, and targeting of specific molecules. Allergen-specific mabs are
      important for the quantification of major allergens in allergen preparations used
      for allergen-specific immunotherapy and allergy diagnosis. Indeed, progress in
      the understanding of the mechanisms of the immunological responses underlying
      allergic disease would not have been possible without the use of mabs.
      Quantification assays are also important in the assessment of environmental
      allergen exposure and monitoring of avoidance procedures.Mabs against human IgE
      provide the basis for various test systems for the detection of specific and
      nonspecific IgE. Mabs raised against IgE or defined cytokines or cytokine
      receptors have potential as neutralizing reagents in vivo for the treatment of
      allergic diseases.Allergen-specific mabs are also valuable tools for the
      localization of allergens within their source material and the characterization
      of allergens derived from natural sources and by recombinant technologies.
      Furthermore they are often used for the isolation of allergens from complex
      extracts by affinity chromatography. The procedure described in this chapter has
      been used successfully to produce mabs against numerous allergens from house dust
      mites, insect venoms, cat, hens egg white, tree-, grass-, and herb pollens, and
      fungi, with the ultimate aim of obtaining matched antibody pairs to establish two
      site binding assays for the quantification of major allergens. The method has
      also been used successfully to generate mabs against human IgE.

PMID- 18612609
TI  - Purification of antibodies.
AB  - Immunoglobulins are a heterogeneous group of proteins. It naturally follows that
      the strategies for purifying them are diverse and numerous. A good knowledge of
      their respective physiochemical properties will obviously make the task easier.
      The choice between using polyclonal and/or monoclonal antibodies will govern the
      basic approach. Each approach will present its own advantages/disadvantages
      including cost, ability to produce a high yield, quality, and a need for
      standardization. The context in which the antibodies will be used is another
      important aspect to consider. When the demand is for establishing
      "ultrasensitive" assays, optimal purity and specificity is obviously required.
      This chapter will focus on the purification of mammalian IgG from polyclonal
      (i.e., rabbit) and monoclonal (i.e., mouse sources). IgG is the principal
      immunoglobulin constituent of mammalian sera. In older animals, it may well
      represent >80% of the total Ig concentration, because of its higher rate of
      synthesis and longer half-life.

PMID- 18612610
TI  - Collection of air samples to quantify exposure to airborne allergens.
AB  - Under normal conditions, airborne allergens are present at very low
      concentrations. Allergens may be carried on relatively large identifiable
      particles such as grains of pollen and mould spores or smaller amorphous
      particles or both. The methods that have been applied to quantify animal airborne
      allergens will be described in this chapter. By careful selection of the air
      sampling equipment and conditions, samples can be collected which quantify, for
      example, the personal exposure of an individual when performing a specific task
      or changes in exposure when allergen control methods are implemented. If as with
      animal allergens, an airborne allergen is not comprised of identifiable
      microscopic fragments, it is necessary to extract the soluble allergen for
      quantification in a specific immunoassay. The basic methods used for the elution
      of animal allergen from polytetrafluoroethylene (PTFE) filters will be described.
      The optimization of this method to suit different allergens and the influence of
      the buffer on extraction efficiency and stability of the allergen during storage
      will also be discussed.

PMID- 18612611
TI  - Assay of air sample eluates.
AB  - After air sampling and elution, the air sample eluate contains an unknown amount
      of allergens together with other materials. The proteins of interest can be
      quantified using immunoassays, which are sensitive, economical, and can be used
      for high throughput. However, the amount of antigen or allergen in an air sample
      may be very low and consequently the assays must be very sensitive and specific.
      Immunoassays use antibodies both to capture and visualize the chosen antigen.
      High specificity and sensitivity can best be achieved by the use of purified,
      characterized, and specific antibodies. It is possible to choose between a wide
      variety of assay setups and reagents. The method described here has been
      developed for the measurement of airborne rodent allergens. It is a
      noncompetitive, two-site (sandwich) EIA that utilizes polyclonal antibodies. The
      detection system uses biotin and streptavidin for increased sensitivity and
      horseradish peroxidase as the substrate with 3,3',5,5'-tetramethylbenzidine (TMB)
      for rapid color development and high sensitivity.

PMID- 18612612
TI  - The Halogen assay--a new technique for measuring airborne allergen.
AB  - The Halogen assay is a new technique for measuring airborne allergen. The assay
      is unique in that it is capable of analyzing allergens and particles together,
      combining the advantages of morphological approaches and immunoassay. The Halogen
      assay allows direct observation of the particles that carry the allergen as well
      as being capable of identifying all the allergen sources an individual is exposed
      and sensitized to. The assay is sensitive because the extracted allergen is bound
      to the membrane at a high local concentration within the minute area around each
      particle and so is easily detected by immunostaining. It is therefore easy to
      detect few pollen grains. The Halogen method supersedes other methods commonly
      used to identify allergens as it is capable of identifying airborne particles
      that are allergen sources.

PMID- 18612613
TI  - Measurement of specific IgG anti-Fel d 1 antibodies.
AB  - There is currently considerable interest in the role of specific IgG antibodies
      in allergy. Several studies suggest that specific IgG antibodies may play a
      protective role in allergy. Successful immunotherapy is associated with increases
      in allergen-specific IgG antibodies which correlate with clinical outcome. Other
      studies have identified an inverse relationship between exposure to cat and
      sensitization, which was associated with high titer specific IgG and IgG(4). This
      immune response was described as a modified Th2 response, because both IgE and
      IgG(4) require Th2 cytokine IL-4 for their production. A modified Th2 response
      was described with laboratory animal allergy, where there was almost a twofold
      reduction in the risk of developing work-related chest symptoms.In this chapter,
      we review the major factors to be considered in the development of an ELISA for
      the determination of specific IgG and IgG(4) antibodies.

PMID- 18612614
TI  - The facilitated antigen binding (FAB) assay--a protocol to measure allergen
      specific inhibitory antibody activity.
AB  - Specific allergen immunotherapy is an effective treatment for IgE-mediated
      allergic disease and involves T- and B-cell mediated events. IgE receptors on the
      surface of antigen-presenting cells facilitate the presentation of allergens in
      the presence of specific IgE antibody resulting in T-cell activation.
      Interference with these IgE-dependent mechanisms by 'blocking' IgG antibodies may
      downregulate T-cell responses and manifest as a reduction in allergic responses
      in vivo. The vigor of proliferative responses by T-cell clones is representative
      of the binding of allergen-IgE complexes to B cells. Therefore, a simplified
      assay can be employed that measures the binding of allergen-IgE complexes to B
      cells instead of a more complex assay involving proliferative assays using
      antigen-specific T-cell clones. Allergen-IgE complexes can be easily detected by
      flow cytometry and this simplified technique is called the IgE-facilitated
      allergen binding (IgE-FAB) assay which is described in this chapter.

PMID- 18612615
TI  - Microscopic identification and purity determination of pollen grains.
AB  - Identification of pollen is like entering a world of great variation in size,
      shape, and structure. To obtain a correct result, a good microscope, basic
      information on pollen grain morphology and a reference sample of the plant to be
      identified are needed. Purity determination of pollen can be performed by
      particle count or by volumetric analysis. In our experience, particle counting is
      the better and most reproducible method and is not greatly influenced by
      interindividual variation. In this chapter, we have described the detailed
      procedure to obtain satisfactory results for identification and determination of
      pollen purity.

PMID- 18612616
TI  - Biopanning for the characterization of allergen mimotopes.
AB  - Proper understanding of the pathogenesis of type I allergy relies on the
      identification of allergen epitopes. The phage display technique is a relatively
      new one to define peptide structures that mimic natural epitopes, including
      conformational B-cell epitopes. Peptides displayed on the phage recognized by an
      antiallergen antibody mimic the physicochemical properties of the amino acids and
      are, therefore, called mimotopes. The main advantage of the biopanning technique
      described in this chapter is that the structure of the antigen/allergen may be
      completely unknown; the only material needed is an antibody binding to it. The
      mimotopes generated by this technique display the features of the
      antigen/allergen but do not crosslink the mast cell-bound IgE-antibodies. Thus
      mimotopes could be used as a safe alternative to the commonly applied allergen
      extracts in immunotherapy of allergic patients and direct the immune response
      toward the desired allergen epitopes. In the selection procedure called
      biopanning, phages with the mimotopes best recognized by the selecting antibody
      are amplified. The titers of phages specifically binding to the selection
      antibody are checked. In this chapter we describe two alternative methods for
      colony screening: the immunoblot and ELISA.

PMID- 18612617
TI  - Identification of mast cells and mast cell subpopulations.
AB  - Mast cells generate mediators of inflammation which are stored in granules and
      secreted on activation either by allergen crosslinking of membrane-bound IgE or
      through other stimuli. Most methods for mast cell identification rely on the
      histochemical detection of constituents of the secretory granules. Although
      staining for mast cells with histochemical stains can be rapid and relatively
      inexpensive, it is not always possible to distinguish reliably between mast cells
      and basophils in tissues. A further problem with the staining of mast cells with
      commonly used basic dyes is that the reagents employed to fix the tissues can
      influence the results, leading to confusion regarding the numbers of mast cells
      present in various tissues. Recognition that there is considerable heterogeneity
      between mast cell populations in the degree to which staining properties are lost
      with formalin fixation has led to mast cell subsets being defined on this basis.
      The development and application of procedures for identifying mast cell proteases
      has led to important advances in our understanding of the role of mast cells and
      in the nature of heterogeneity in man. The techniques described here should allow
      the reliable detection of mast cells and mast cell subsets in a range of tissues
      and cell preparations. There will be a continuing need for validation, for
      consideration of potential sources of error, and for the development of new and
      more reliable techniques for mast cell identification.

PMID- 18612618
TI  - Purification and characterization of mast cell tryptase and chymase from human
      tissues.
AB  - Mast cells are key effector cells of the allergic response. When stimulated by
      specific allergen through the high-affinity IgE receptors or through other
      stimuli, these cells release a number of potent mediators of inflammation.
      Amongst these are the serine proteases tryptase and chymase. In humans, tryptase
      is the most abundant mediator stored in mast cells. Chymase is present in more
      moderate amounts in a subpopulation of mast cells (MC(TC)). This subtype of mast
      cells predominates in connective tissue, whereas the other major subtype, the
      MC(T), predominates in mucosal tissue. Both proteases have been shown to act on
      specific extracellular proteins and peptides, as well as to alter the behavior of
      various cell types. Inhibitors of tryptase have been found to be efficacious in
      animal and human models of asthma, and both proteases are currently being
      investigated as potential targets for therapeutic intervention. Such
      pharmacological, physiological, and biochemical studies require the availability
      of purified tryptase and chymase. In this chapter, we shall describe procedures
      for the purification of tryptase and chymase from human tissues and provide
      protocols for monitoring purification and characterization of the final product.
      The preparation of recombinant proteases will not be covered, though some of the
      procedures described may be readily adapted for their purification from
      recombinant expression systems. The procedures described here have been developed
      for the purification of the human proteases and will require some modification if
      applied to purify mast cell proteases from the tissues of other species.

PMID- 18612619
TI  - Experimental activation of mast cells and their pharmacological modulation.
AB  - The activation of mast cells is of pivotal importance in the pathogenesis of
      allergic conditions. Mast cell activation can provoke rapid increases in
      microvascular permeability, induce bronchoconstriction after blood flow,
      stimulate the recruitment and activation of other inflammatory cells, and has
      come to be associated with the processes of tissue remodeling and fibrosis. Such
      changes may be mediated by the release of a range of potent mediators of
      inflammation: preformed in secretory granules, or newly generated, or both. There
      are major differences in the responsiveness to various stimuli and to
      pharmacological agents for mast cells from different body compartments. A method
      is presented here for the purification of mast cells from enzymatically dispersed
      human tissues. The methods described for the experimental activation of mast
      cells can be readily adapted to studies with cell lines or mast cells obtained
      through long-term culture.

PMID- 18612620
TI  - In situ Hybridization.
AB  - Hybridization is the formation of hybrid nucleic acid molecules with
      complementary nucleotide sequences in DNA:DNA, DNA:RNA, or RNA:RNA forms. In situ
      hybridization is a highly sensitive technique that allows detection and
      localization of specific DNA or RNA molecules in morphologically preserved
      isolated cells, histological tissue sections, or chromosome preparations. In situ
      hybridization has broad range of applications and has been used to (a) localize
      viral infection, (b) identify sites of gene expression, (c) analyze mRNA
      transcription and tissue distribution, and (d) map gene sequences in chromosomes.
      There are several advantages of the use of in situ hybridization including the
      fact that it can be applied to archival materials and frozen tissues and can be
      combined with immunohistochemistry to detect protein as well as mRNA of interest
      or phenotype of cells expressing the target genome, detecting more than one
      nucleic acid sequences using different labeling methods.The major steps involved
      in in situ hybridization are as follows: probe preparation and labeling, tissue
      fixation, permeabilization, hybridization, and signal detection and these are
      described in detail in this chapter.

PMID- 18612621
TI  - [Surgery for Echinococcus cysts in the liver].
AB  - Hydatid disease is a parasitic infection caused by Echinococcus granulosus, and
      the most frequently affected organ is the liver. Diagnosis is usually based on
      radiological and serological findings. Even though percutaneous drainage and
      medical therapies are suggested for selected cases, for the most part surgery is
      required. The surgical strategy consists of killing the cyst, removing its
      contagious elements from the liver, obliterating the cystic cavity, and
      preventing recurrence and complications. A large spectrum of operations - from
      simple drainage to liver transplantation - has been proposed for reaching these
      objectives. Laparoscopic surgery is used increasingly for hydatid disease. This
      article reviews the current status of hydatid disease surgery, with special
      emphasis on liver cysts.

PMID- 18612622
TI  - Productively combining proteasome inhibition with the immunotherapy of cancer.

PMID- 18612623
TI  - Continuing on the road to health: a short history of the Charite
      universitatsmedizin Berlin from a plague house in the past to a medical school
      with a future.

PMID- 18612624
TI  - [X-ray mammography : calcifications, masses and architectural distortions].
AB  - Mammography, breast ultrasound and MRI of the breast are the most relevant
      diagnostic tools in the early detection of breast cancer. In this context,
      mammography is superior to the other imaging modalities in the depiction of tumor
      associated microcalcifications. Moreover, this method reliably depicts masses
      within lipomatous surrounding tissue. However, in patients with dense parenchyma
      (type III and IV according to the American College of Radiology, ACR),
      mammography is limited in the detection of non-calcified carcinoma. Here, the
      sensitivity for diagnosis of breast cancer decreases to less than 50%. In
      conclusion, the diagnosis of breast carcinoma on mammograms is based on the
      depiction of pleomorphic or fine-linear microcalcifications, irregularly shaped
      masses with ill-defined or spiculated borders and focal architectural
      distortions.

PMID- 18612625
TI  - Mapping of isolate-specific QTLs for clubroot resistance in Chinese cabbage
      (Brassica rapa L. ssp. pekinensis).
AB  - A number of clubroot resistant (CR) Chinese cabbage cultivars have been developed
      in Japan using resistant genes from CR European fodder turnips (B. rapa ssp.
      rapifera). Clubroot resistance in European fodder turnips are known to be
      controlled by the combined action of several dominant resistance genes. We have
      developed three Chinese cabbage clubroot-resistant doubled haploid (DH) lines-
      T136-8, K10, and C9--which express resistance in different manners against two
      isolates of Plasmodiophora brassicae, M85 and K04. Depending on the isolates, we
      identified two CR loci, CRk and CRc. CRk was identified by quantitative trait
      loci (QTL) analysis of an F(2) population derived from a cross between K10 and
      Q5. This locus showed resistance to both isolates and is located close to Crr3 in
      linkage group R3. The other locus, CRc was identified by QTL analysis of an F(2)
      population derived from a cross between C9 and susceptible DH line, 6R. This
      locus was mapped to linkage group R2 and is independent from any published CR
      loci. We developed sequence-tagged site markers linked to this locus.

PMID- 18612626
TI  - The role of macrophage migration inhibitory factor on glucose metabolism and
      diabetes.
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine
      involved in many inflammatory reactions and disorders, and it has become evident
      that it also affects glucose homeostasis. The protein is produced by pancreatic
      beta cells and can promote the release of insulin. It also modulates glucose
      uptake, glycolysis and insulin resistance in insulin target cells such as the
      adipocyte, myocyte and cardiomyocyte. Possessing both immunological and
      endocrinological properties, MIF has been associated with the development of type
      1 and type 2 diabetes, and it may be important in the setting of islet
      transplantation. The present review summarises our current knowledge, based on
      clinical and research data, on the impact of MIF on both physiological and
      pathological aspects of glucose metabolism.

PMID- 18612627
TI  - Effects of mannitol alone and mannitol plus furosemide on renal oxygen
      consumption, blood flow and glomerular filtration after cardiac surgery.
AB  - OBJECTIVE: Imbalance of the renal medullary oxygen supply/demand relationship can
      cause hypoxic medullary damage and ischaemic acute renal failure (ARF). The use
      of mannitol for prophylaxis/treatment of clinical ischaemic ARF is controversial
      and the effect of mannitol on renal oxygenation in man has not yet been
      investigated. We evaluated the effects of mannitol on renal oxygen consumption
      (RVO(2))(,) renal blood flow (RBF) and glomerular filtration rate (GFR) in
      postoperative patients. DESIGN: Prospective interventional study. SETTING:
      University hospital cardiothoracic ICU. PATIENTS: Ten uncomplicated mechanically
      ventilated and sedated postcardiac surgery patients with preoperatively normal
      renal function. INTERVENTIONS: Mannitol infusion (225 mg/kg + 75 mg/kg/h) and
      combined mannitol and furosemide infusion (0.25 mg/kg + 0.25 mg/kg/h).
      MEASUREMENTS AND RESULTS: Systemic haemodynamics were evaluated by a pulmonary
      artery catheter. RBF and GFR were measured by the renal vein thermodilution
      technique and by renal extraction of (51)Cr-EDTA, respectively. Mannitol
      increased urine flow (60%), GFR (20%) and filtration fraction (FF) (20%) with no
      change in RBF. This was accompanied by an increase in renal sodium reabsorption
      (18%), RVO(2) (19%) and renal oxygen extraction (21%). When combined with
      mannitol, furosemide normalised sodium reabsorption, RVO(2), renal oxygen
      extraction with no change in RBF, while GFR and FF were still elevated compared
      to control. CONCLUSIONS: In patients with normal renal function, mannitol
      increases GFR, which increases tubular sodium load, sodium reabsorption and
      RVO(2) after cardiac surgery. The lack of effect on RBF, indicates that mannitol
      impairs the renal oxygen supply/demand relationship. Furosemide normalised renal
      oxygenation when combined with mannitol.

PMID- 18612629
TI  - Theme-based modular approach for delivering the undergraduate analytical
      chemistry curriculum.

PMID- 18612628
TI  - Effects of acute and chronic aripiprazole treatment on choice between cocaine
      self-administration and food under a concurrent schedule of reinforcement in
      rats.
AB  - RATIONALE: Dopamine D2-like partial agonists such as aripiprazole have received
      some attention as potential pharmacotherapies for the treatment of
      psychostimulant addiction. However, the preclinical evaluations so far have
      focused on acute effects of aripiprazole. OBJECTIVES: We tested the hypothesis
      that aripiprazole, both as acute and as chronic treatment, would preferentially
      decrease cocaine self-administration while sparing behavior maintained by a
      natural reinforcer, resulting in a shift in the allocation of behavior from
      cocaine-taking towards the alternative reinforcer. MATERIALS AND METHODS: Rats
      were trained to self-administer intravenous cocaine in a concurrent choice
      procedure, with a palatable food as the competing reinforcer, under a fixed ratio
      (FR) 1 FR 5 chain schedule. Aripiprazole was then administered as continuous
      infusion by osmotic minipumps for 5 days, during which performance in the choice
      procedure was assessed daily. RESULTS: An intermediate dose of aripiprazole
      decreased cocaine self-administration and shifted the cocaine choice curve to the
      right as an acute treatment. However, as a chronic treatment, aripiprazole failed
      to decrease cocaine self-administration or cocaine choice, despite a dose
      dependent decrease in overall response rates and food-maintained behavior.
      CONCLUSIONS: Our results confirm and extend earlier findings and indicate that
      acute administration of aripiprazole can decrease cocaine self-administration.
      However, based on the present data, chronic treatment with aripiprazole does not
      show much promise as a potential pharmacotherapy for cocaine addiction. Both
      acute and chronic treatment data are in agreement with published clinical
      findings, suggesting that the concurrent choice procedure in rats has predictive
      validity of efficacy in humans.

PMID- 18612630
TI  - Grip force control during gait initiation with a hand-held object.
AB  - When walking with a hand-held object, grip force is coupled in an anticipatory
      manner to changes in inertial force resulting from the accelerations and
      decelerations of gait. However, it is not known how grip and inertial forces are
      organized at the onset of gait, and if the two forces are coupled in the early
      phases of gait initiation. Moreover, initiating walking with an object involves
      the coordination of anticipatory postural (e.g., ground reaction force changes)
      and grasping adjustments. The aim of this study was to investigate the
      relationship of ground reaction, grip, and inertial force onsets, and the
      subsequent development of the coupling of grip and inertial forces during gait
      initiation with a hand-held object. Ten subjects performed gait initiation with a
      hand-held object following predictable and unpredictable start signals. We found
      that ground reaction and grip force onsets were closely linked in time regardless
      of the predictability of the start signal. In the early period of gait
      initiation, the grip force started to increase prior to inertial force changes.
      While the strength of the coupling of grip and inertial forces was moderate in
      this early phase, it increased to values observed during steady-state gait after
      the swing foot left the ground. The early grip force increase and the coupling of
      grip and inertial forces represent an anticipatory control process. This process
      establishes an appropriate grip-inertial force ratio to ensure object stability
      during acceleration after foot-off and maintains this increased ratio thereafter.
      The results suggest that grasping and whole body movements are governed by a
      common internal representation.

PMID- 18612632
TI  - Imaging findings in right-sided diverticulitis in a child.
AB  - We report the imaging findings in a case of acute right-sided diverticulitis in a
      13-year-old boy. Based on this diagnosis the patient was successfully treated
      conservatively with intravenous antibiotics. This entity should be considered in
      patients with right lower quadrant pain and a sonographically normal appendix,
      particularly in those of Asian or Pacific descent.

PMID- 18612631
TI  - Coordination strategies for limb forces during weight-bearing locomotion in
      normal rats, and in rats spinalized as neonates.
AB  - Some rats spinally transected as neonates (ST rats) achieve weight-supporting
      independent locomotion. The mechanisms of coordinated hind-limb weight support in
      such rats are not well understood. To examine these we compared ST rats (with
      better than 60% of weight supported steps) and normal rats that were trained to
      cross an instrumented runway. Ground reaction forces, coordination of hind-limb
      and forelimb forces and the motions of the center of pressure (CoP) were
      assessed. Normal rats crossed the runway with a diagonal trot. On average hind
      limbs bore about 80% of the vertical load carried by forelimbs (45% body weight
      on hind-limbs 55% on forelimbs), although this varied. Forelimbs and hind-limbs
      acted synergistically to generate decelerative and propulsive rostrocaudal
      forces, which averaged 15% of body weight with maximums of 50%. Lateral forces
      were very small (<8% of body weight). Center of pressure progressed in jumps
      along a straight line with mean lateral deviations <1 cm. ST rats hind-limbs bore
      about 60% of the vertical load of forelimbs (37% body weight on hind-limbs, 63%
      on forelimbs), significantly less compared to intact rats (P < 0.05). ST rats
      showed similar mean rostrocaudal forces, but with significantly larger maximum
      fluctuations of up to 80% of body weight (P < 0.05). Joint force-plate recordings
      showed forelimbs and hind-limb rostrocaudal forces in ST rats were opposing and
      significantly different from intact rats (P < 0.05). Lateral forces were
      approximately 20% of body weight and significantly larger than in normal rats (P
      < 0.05). Center of pressure zig-zagged, with mean lateral deviations of
      approximately 2 cm and a significantly larger range (P < 0.05). The haunches were
      also observed to roll more than normal rats. The locomotor strategy of injured
      rats using limbs in opposition was presumably less efficient but their complex
      gait was statically stable. Because forelimbs and hind-limbs acted in opposition,
      the trunk was held compressed. Force coordination was likely managed largely by
      the voluntary control in forelimbs and trunk.

PMID- 18612633
TI  - Transmission photoemission electron microscopy for lateral mapping of the X-ray
      absorption structure of a metalloprotein in a liquid cell.
AB  - We use photoemission electron microscopy in an X-ray transmission mode for full
      field imaging of the X-ray absorption structure of copper in the respiratory
      metalloprotein hemocyanin KLH1. It contains 160 oxygen binding sites. Each site
      reversibly binds one molecule oxygen between two copper atoms. In our setup,
      hemocyanin is dissolved in aqueous solution and enclosed in an ultra-high vacuum
      compatible liquid sample cell with silicon nitride membranes. The local X-ray
      absorption structure of the liquid sample is converted into photoelectrons at the
      microscope side of the cell acting as a photocathode. In this way, different
      copper valencies are laterally distinguished under in vivo-like conditions,
      attributed to Cu(I) in the deoxy-state and Cu(II) in the oxy-state.

PMID- 18612634
TI  - MAIDS resistance-associated gene expression patterns in secondary lymphoid
      organs.
AB  - Murine acquired immunodeficiency syndrome (MAIDS) is caused by exposure to murine
      leukemia virus and serves as a model to study human AIDS. In MAIDS-susceptible
      C57BL/6 mice, virus exposure leads to progressive immune deficiency, while
      resistant strains such as BALB/c recover from infection and develop protective
      immunity. The goal of this study was to identify early gene expression patterns
      that may be important in establishing this strain-specific differential response.
      Total RNA was isolated from spleens and pooled lymph nodes of both mouse strains
      at 3 and 7 days post virus infection. The complementary DNA generated from this
      RNA was hybridized to mouse oligonucleotide DNA microarrays using a strategy that
      controlled for inherent variability and highlighted only virus-induced changes.
      Fluorescent intensities were normalized and analyzed for statistically
      significant differential expression between strains across both time points and
      lymphoid organs. The majority of the resistance-associated genes was identified
      at day 3 post-infection and demonstrated the highest fold differences between
      strains, while more susceptibility-associated sequences were seen at 7 days post
      infection. Among the most highly differentially expressed sequences seen at the
      earlier time point were genes related to protein metabolism, especially serine
      proteases. Differential patterns of chemokine-related genes were observed at the
      later time point. The overall pattern of expression suggests strain-specific
      differences in proteases and chemokines within secondary lymphoid organs shortly
      after infection influence the likelihood of disease progression.

PMID- 18612636
TI  - A new tyrosinase epitope recognized in the HLA-B*4002 context by CTL from
      melanoma patients.
AB  - Melanoma reactive CTL were obtained by stimulating PBL from a melanoma patient in
      remission since 1994 following adjuvant TIL immunotherapy, with the autologous
      melanoma cell line. They were cloned by limiting dilution. One CTL clone
      recognized melanoma cell lines expressing tyrosinase and the B*4002 molecule,
      either spontaneously or upon transfection. We demonstrated that this clone
      recognizes the tyrosinase-derived nonapeptide 316-324 (ADVEFCLSL) and the
      overlapping decapeptide 315-324 (SADVEFCLSL). We derived two distinct additional
      specific CTL clones from this same patient that were also reactive against B*4002
      melanoma cell lines, suggesting a relative diversity of this specific repertoire
      in this patient. Stimulating PBMC derived from four additional B*4002 melanoma
      patients with the tyrosinase 316-324 nonapeptide induced the growth of specific
      cells for two of the patients, demonstrating the immunogenicity of this new
      epitope. Our data show that this nonapeptide is a new tool that could be used to
      generate melanoma-specific T cells for adoptive immunotherapy or serve as a
      peptide vaccine for HLA-B*4002 melanoma patients.

PMID- 18612637
TI  - Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy:
      a commentary.
AB  - The various immunological roles of human alpha-fetoprotein (HAFP), and its
      correlation with hepatomas, that is, hepatocellular carcinomas (HCCs), are not
      often addressed together in biomedical reports considering that HAFP is an
      established biomarker for hepatomas. Studies reporting measurement of HAFP serum
      levels in hepatoma patients in basic/clinical research settings has greatly
      increased over the years. Recent reports have now expanded our base knowledge in
      the mounting of an immune response against AFP, a self antigen, during hepatoma
      tumorigenesis. Advances in the detection and identification of AFP-derived
      peptide epitopes are opening new vistas of knowledge regarding the immunological
      role of AFP-peptides as T cell stimulating antigens in the course of hepatoma
      growth and progression. The present commentary addresses HAFP-derived peptides as
      immunologic responders in HCC and their use in the study and generation of AFP
      peptide sensitized T cells directed against hepatoma cells. Attempts were further
      made to relate the AFP-derived peptide epitopes to T cell activities during the
      course of hepatoma immunotherapies and to profile the traits and properties of
      the peptides themselves. Hence, the present commentary was divided into two
      sections; (1) the characterization, properties, and traits of AFP peptide
      epitopes, and (2) the use of AFP-derived peptides in the therapeutic induction of
      T cells primed against hepatoma cells using both in vivo and in vitro models.

PMID- 18612635
TI  - Mass spectral data for 64 eluted peptides and structural modeling define peptide
      binding preferences for class I alleles in two chicken MHC-B haplotypes
      associated with opposite responses to Marek's disease.
AB  - In the chicken, resistance to lymphomas that form following infection with
      oncogenic strains of Marek's herpesvirus is strongly linked to the major
      histocompatibility complex (MHC)-B complex. MHC-B21 haplotype is associated with
      lower tumor-related mortality compared to other haplotypes including MHC-B13. The
      single, dominantly expressed class I gene (BF2) is postulated as responsible for
      the MHC-B haplotype association. We used mass spectrometry to identify peptides
      and structural modeling to define the peptide binding preferences of BF2 2101 and
      BF2 1301 proteins. Endogenous peptides (8-12 residues long) were eluted from
      affinity-purified BF2 2101 and BF2 1301 proteins obtained from transduced cDNA
      expressed in RP9 cells, hence expressed in the presence of heterologous TAP.
      Sequences of individual peptides were identified by mass spectrometry. BF2 2101
      peptides appear to be tethered at the binding groove margins with longer peptides
      arching out but selected by preferred residues at positions P3, P5, and P8: X-X
      [AVILFP]-X((1-5))-[AVLFWP]-X((2-3))-[VILFM]. BF2 1301 peptides appear selected
      for residues at P2, P3, P5, and P8: X-[DE]-[AVILFW]-X((1-2))-[DE]-X-X-[ED]-X((0
      4)). Some longer BF2 1301 peptides likely also arch out, but others are
      apparently accommodated by repositioning of Arg83 so that peptides extend beyond
      the last preferred residue at P8. Comparisons of these peptides with earlier
      peptides derived in the presence of homologous TAP transport revealed the same
      side chain preferences. Scanning of Marek's and other viral proteins with the BF2
      2101 motif identified many matches, as did the control human leukocyte antigen A
      0201 motif. The BF2 1301 motif is more restricting suggesting that this allele
      may confer a selective advantage only in infections with a subset of viral
      pathogens.

PMID- 18612638
TI  - A population-based study of prevalence and hospital charges in total hip and knee
      replacement.
AB  - The purpose of this study was to explore the increasing prevalence of factors
      affecting hospital charges for primary total hip replacement/total knee
      replacement (THR/TKR). This study analysed 37,918 THR and 76,727 TKR procedures
      performed in Taiwan from 1996 to 2004. Odds ratio (OR) and effect size (ES) were
      calculated to assess the relative change rate. Multiple regression models were
      employed to predict hospital charges. The following factors were associated with
      increased hospital charges: age younger than 65 years old; increased disease
      severity (Charlson comorbidity index [CCI] = 1 or > or = 2); absence of primary
      diagnoses of osteoarthritis (OA), rheumatoid arthritis (RA), avascular necrosis
      (AVN); treatment at a hospital or by a surgeon performing a high volume of
      operations; and longer average length of stay (ALOS). The Bureau of National
      Health Insurance (BNHI) should ensure that surgeons take precautionary measures
      to minimise complications and maximise quality of life after surgery. Use of
      joint prostheses from different manufacturers can reduce costs without
      compromising patient satisfaction.

PMID- 18612641
TI  - [Active surveillance of localized prostate cancer. Significance of prostate core
      needle biopsies].
AB  - Today, more than 80% of men diagnosed with prostate cancer (PCA) by PSA screening
      do not die from the sequelae of their disease. About 70% present with early,
      organ-confined cancer and almost half of them are small (<5 cm(3)) without
      evidence of progression over years (insignificant PCA). It is assumed that
      screening brings the diagnosis of PCA forward by about 9 years and that in almost
      one third of these cases immediate radical prostatectomy or radiotherapy would
      result in overtreatment. Thus, the treatment strategy of "active surveillance"
      with selective but delayed intervention for patients with organ-confined PCA
      could be an attractive alternative to the known curative therapy options.
      However, a prerequisite of such a therapeutic approach would be a precise
      identification of patients at high risk for cancer progression. Careful work-up
      of prostate core needle biopsies including improved pre-embedding preparation and
      detailed interpretation are of the utmost importance. A Gleason score < or =6 and
      tumor in only one or two cores are considered predictive of organ-confined
      cancer. Pathologists should concentrate on correct Gleason scoring in core needle
      biopsies and identification of lesions that exclude a patient from active
      surveillance.

PMID- 18612640
TI  - Models for actin polymerization motors.
AB  - Actin polymerization drives cell membrane protrusions and the propulsion of
      intracellular pathogens. The molecular mechanisms driving actin polymerization
      are not yet fully understood. Various mathematical models have been proposed to
      explain how cells convert chemical energy released upon actin polymerization into
      a pushing force on a surface. These models have attempted to explain puzzling
      properties of actin-based motility, including persistent attachment of the
      network to the membrane during propulsion and the interesting trajectories of
      propelled particles. These models fall generally into two classes: those
      requiring filament (+)-ends to fluctuate freely from the membrane to add
      subunits, and those where filaments elongate with their (+)-ends persistently
      associated with surface through filament end-tracking proteins ("actoclampin"
      models). This review compares and contrasts the key predictions of these two
      classes of models with regard to force-velocity profiles, and evaluates them with
      respect to experiments with biomimetic particles, and the experimental evidence
      on the role of end-tracking proteins such as formins and nucleation-promoting
      factors in actin-based motility.

PMID- 18612642
TI  - Arabidopsis dynamin-related protein DRP2B is co-localized with DRP1A on the
      leading edge of the forming cell plate.
AB  - The Arabidopsis genome has six families of dynamin-related proteins. One of these
      families includes DRP2A and DRP2B. The domain structures of proteins of this
      family are most similar to those of the animal endocytosis protein, dynamin. In
      this study, the signals of GFP-tagged DRP2B were strongly detected in the cell
      plate of Arabidopsis root tip cells and tobacco cultured cells. Time-lapse
      observations of these signals during cytokinesis in tobacco cultured cells
      suggested that DRP2B mainly localized to the newly formed part of the cell plate,
      and that the localization dynamics of DRP2B was quite similar to that of DRP1A,
      which is an Arabidopsis dynamin-related protein that is closely related to
      soybean phragmoplastin. These results indicate that Arabidopsis dynamin-related
      proteins, DRP1A and DRP2B, from two different families, participate in membrane
      remodeling at a similar place in the cell plate.

PMID- 18612643
TI  - Array and distribution of actin filaments in guard cells contribute to the
      determination of stomatal aperture.
AB  - Actin filaments in guard cells and their dynamics function in regulating stomatal
      movement. In this study, the array and distribution of actin filaments in guard
      cells during stomatal movement were studied with two vital labeling,
      microinjection of alexa-phalloidin in Vicia faba and expression of GFP-mTn in
      tobacco. We found that the random array of actin filaments in the most of the
      closed stomata changed to a ring-like array after stomatal open. And actin
      filaments, which were throughout the cytoplasm of guard cells of closed stomata
      (even distribution), were mainly found in the cortical cytoplasm in the case of
      open stomata (cortical distribution). These results revealed that the random
      array and even distribution of actin filaments in guard cells may be required for
      keeping the closed stomata; similarly, the ring-like array and cortical
      distribution of actin filaments function in sustaining open stomata. Furthermore,
      we found that actin depolymerization, the trait of moving stomata, facilitates
      the transformation of actin array and distribution with stomatal movement. So,
      the depolymerization of actin filaments was favorable for the changes of actin
      array and distribution in guard cells and thus facilitated stomatal movement.

PMID- 18612644
TI  - A history of plant biotechnology: from the Cell Theory of Schleiden and Schwann
      to biotech crops.
AB  - Plant biotechnology is founded on the principles of cellular totipotency and
      genetic transformation, which can be traced back to the Cell Theory of Matthias
      Jakob Schleiden and Theodor Schwann, and the discovery of genetic transformation
      in bacteria by Frederick Griffith, respectively. On the 25th anniversary of the
      genetic transformation of plants, this review provides a historical account of
      the evolution of the theoretical concepts and experimental strategies that led to
      the production and commercialization of biotech (transformed or transgenic)
      plants expressing many useful genes, and emphasizes the beneficial effects of
      plant biotechnology on food security, human health, the environment, and
      conservation of biodiversity. In so doing, it celebrates and pays tribute to the
      contributions of scores of scientists who laid the foundation of modern plant
      biotechnology by their bold and unconventional thinking and experimentation. It
      highlights also the many important lessons to be learnt from the fascinating
      history of plant biotechnology, the significance of history in science teaching
      and research, and warns against the danger of the growing trends of ignoring
      history and historical illiteracy.

PMID- 18612645
TI  - [On the use of autologous serum eyedrops in Germany : results of a survey among
      members of the Cornea Section of the German Ophthalmological Society (DOG)].
AB  - PURPOSE: The use of serum eye drops has become more common for treating ocular
      surface diseases such as persistent epithelial defect and dry eye. For the
      production and use of blood products, regulatory restrictions apply. We surveyed
      the practice of production and application of serum eyedrops among the members of
      the Cornea Section of the German Ophthalmological Society (DOG) in Germany.
      METHODS: A questionnaire concerning the application of topical blood-derived
      therapeutic agents for use in the eye was sent to 103 institutions in 2005 and
      2007. The questionnaire included 14 groups of questions. RESULTS: The rate of
      response was 49% in 2005 and 55% in 2007. Sixty-five percent (2005: 48%) of the
      institutions used blood-derived products as therapeutic agents in the eye (in
      96%, serum eye drops). In 2007, 17% of the centers stated that they had a license
      to produce serum eye drops according to the official regulations (2005: 10%).
      Three hospitals stopped using serum eyedrops for regulatory reasons. In 2007
      1,237 patients were treated (2005: 1,389); 36% of the ophthalmic departments
      produced the serum eye drops themselves (2005: 55%) and 43% produced them in
      cooperation together with or exclusively in another institution. Quality controls
      (e.g., virus serology and sterility checks) were performed in 47% (2005: 24%). In
      2005, one corneal fibrin deposit was described. In 2007, no complication was
      reported. CONCLUSION: Although fewer patients were treated in total in 2007, the
      number of centers using serum eye drops increased between 2005 and 2007. Serious
      complications were not described. Some hospitals stopped the production and use
      of serum eye drops because of regulatory reasons or had the drops produced by
      nonophthalmic institutions with a license to produce blood-derived products. In
      view of prospective randomized clinical trials showing that autologous serum
      support ocular surface wound healing, this therapy should be accepted as a
      standard of care.

PMID- 18612646
TI  - Cortical desmoid and the four clinical scenarios.
AB  - We reviewed four patients diagnosed with a cortical desmoid lesion at the distal
      posterior medial femur. Each case reflects a clinical scenario that can be
      present. Cortical desmoid is a benign, self-limited entity which occasionally can
      exhibit aggressive radiologic features. Here, we present the specific imaging
      features in association with patients history and clinical findings facilitating
      establishment of correct diagnosis. Exact diagnosis is important in order to
      avoid unnecessary biopsy and complicated therapeutic strategies.

PMID- 18612647
TI  - Ivory identification by DNA profiling of cytochrome b gene.
AB  - Ivory can be visually identified in its native form as coming from an elephant
      species; however, determining from which of the three extant elephant species a
      section of ivory originates is more problematic. We report on a method that will
      identify and distinguish the protected and endangered elephant species, Elephas
      maximus or Loxodonta sp. To identify the species of elephant from ivory products,
      we developed three groups of nested PCR amplifications within the cytochrome b
      gene that generate amplification products using highly degraded DNA isolated from
      confiscated ivory samples dating from 1995. DNA from a total of 382 out of 453
      ivory samples were successfully isolated and amplified leading to species
      identification. All sequences were searched against GenBank and found to match
      with E. maximus and Loxodonta sp. with at least 99% similarity. The samples that
      were tested came from eight Asian elephants, 14 African forest elephants
      (Loxodonta cyclotis), and 360 African savannah elephants (Loxodonta africana).
      This study demonstrates a high success rate in species identification of ivory by
      a nested PCR approach within the cytochrome b gene which provides the necessary
      information for the protection of endangered species conservation.

PMID- 18612648
TI  - Comparative karyological analysis of three members of Allocreadiidae (Digenea):
      taxonomic and phylogenetic implications.
AB  - Chromosome number and morphology were studied in three allocreadiid species from
      mitotic metaphases of intramolluscan stages using karyometric analysis. Bunodera
      luciopercae has a diploid number 2n=14, with two large pairs of metacentrics, one
      pair of submeta-subtelocentrics, and four pairs of acrocentrics. Karyotype of
      Allocreadium isoporum, 2n=14, with two large pairs of metacentrics and five pairs
      of acrocentrics was recognized to be closely related to that of B. lucioperca.
      The most conspicuous interspecific difference occurs in the centromere position
      of the chromosomes of the pair 3. The possible reasons of the discrepancies
      between data reported therein and the karyological information previously
      published on these two species are discussed. Crepidostomum sp. has 2n=12, with
      one pair of large metacentrics and five pairs of acrocentrics and is more
      distantly related karyologically to the other two members of the family.
      Evolutionary considerations based on comparison of the chromosomes of
      Allocreadiidae and other studied families of the suborder Xiphidiata suggest that
      allocreadiids are karyotypically distinct. The placement of Allocreadiidae and
      Opecoelidae in the superfamily Allocreadioidea is questioned.

PMID- 18612649
TI  - Isolation, analysis and marker utility of novel miniature inverted repeat
      transposable elements from the barley genome.
AB  - Four previously undescribed families of miniature inverted repeat transposable
      elements (MITEs) were isolated by searching barley genomic DNA using structure
      based criteria. Putative MITEs were confirmed by PCR to determine their
      insertional polymorphism in a panel of diverse barley germplasm. Copy numbers for
      all these familes are somewhat low (less than 1,000 copies per family per haploid
      genome). In contrast to previous studies, a higher proportion of insertions of
      the new MITEs are found within known transposable elements (27%) than are
      associated with genes (15%). Preliminary studies were conducted on two of the new
      MITE families to test their utility as molecular markers. Insertional
      polymorphism levels for both the families are high and diversity trees produced
      by both the families are similar and congruent with known relationships among the
      germplasm studied, suggesting that both the MITE families are useful markers of
      barley genetic diversity.

PMID- 18612651
TI  - Behaviour and resource use of two competing vole species under shared predation
      risk.
AB  - Indirect interaction between two competing species via a shared predator may be
      an important determinant of population and community dynamics. We studied the
      effect of predation risk imposed by the least weasel Mustela nivalis nivalis on
      space use, foraging and activity of two competing vole species, the grey-sided
      vole Myodes rufocanus, and the bank vole Myodes glareolus. The experiment was
      conducted in a large indoor arena, consisting of microhabitat structures
      providing food, shelter, trees for refuge and separated areas with high and low
      predation risk. Voles were followed for 5 days: 2 days before, 1 day during and 2
      days after the presence of weasel. Our results suggest an effect of weasel
      presence on the vole community. Voles of both species shifted their activity from
      risky to less risky areas, climbed trees more often and were less active. Seed
      consumption was not affected by weasel presence. The time spent in the risky and
      less risky area did not differ between species, but bank voles spent more time in
      trees than grey-sided voles. Males of both species were more exposed to predation
      risk than females, i.e. generally spent more time in the risky area. Proportion
      of time spent in the risky area, the use of area, trees and food stations were
      sex dependent. Activity and use of trees were species dependent. We found no
      evidence for despotic distribution between our two species, although bank voles
      seemed to be more affected by coexistence, since they lost weight during the
      experiment. Based on our results we conclude that predator response was largely
      similar between species, while the sex-specific responses dominated. Besides a
      stronger escape response in the bank vole, the strongest individual differences
      were sex specific, i.e. males were more prone to take risks in space use and
      activity.

PMID- 18612652
TI  - Higher masseter muscle mass in grazing than in browsing ruminants.
AB  - Using cranioskeletal measurements, several studies have generated evidence that
      grazing ruminants have a more pronounced mastication apparatus, in terms of
      muscle insertion areas and protuberances, than browsing ruminants, with the
      resulting hypothesis that grazers should have larger, heavier chewing muscles
      than browsers. However, the only investigation of this so far [Axmacher and
      Hofmann (J Zool 215:463-473, 1988)] did not find differences between ruminant
      feeding types in the masseter muscle mass of 22 species. Here, we expand the
      dataset to 48 ruminant species. Regardless of phylogenetic control in the
      statistical treatment, there was a significant positive correlation of body mass
      and masseter mass, and also a significant association between percent grass in
      the natural diet and masseter mass. The results support the concept that ruminant
      species that ingest more grass have relatively larger masseter muscles, possibly
      indicating an increased requirement to overcome the resistance of grass forage.
      The comparative chewing resistance of different forage classes may represent a
      rewarding field of ecophysiological research.

PMID- 18612650
TI  - Functional genomics of monensin sensitivity in yeast: implications for post-Golgi
      traffic and vacuolar H+-ATPase function.
AB  - We have screened a complete collection of yeast knockout mutants for sensitivity
      to monensin, an ionophore that interferes with intracellular transport. A total
      of 63 sensitive strains were found. Most of the strains were deleted for genes
      involved in post-Golgi traffic, with an emphasis on vacuolar biogenesis. A high
      correlation was thus seen with VPS and VAM genes, but there were also significant
      differences between the three sets of genes. A weaker correlation was seen with
      sensitivity to NaCl, in particular rate of growth effects. Interestingly, all 14
      genes encoding subunits of the vacuolar H(+)-ATPase (V-ATPase) were absent in our
      screen, even though they appeared in the VPS or VAM screens. All monensin
      sensitive mutants that could be tested interact synthetically with a deletion of
      the A subunit of the V-ATPase, Vma1. Synthetic lethality was limited to mutations
      affecting endocytosis or retrograde transport to Golgi. In addition, vma1 was
      epistatic over the monensin sensitivity of vacuolar transport mutants, but not
      endocytosis mutants. Deletions of the two isoforms of the V-ATPase a subunit,
      Vph1 and Stv1 had opposite effects on the monensin sensitivity of a ypt7 mutant.
      These findings are consistent with a model where monensin inhibits growth by
      interfering with the maintenance of an acidic pH in the late secretory pathway.
      The synthetic lethality of vma1 with mutations affecting retrograde transport to
      the Golgi further suggests that it is in the late Golgi that a low pH must be
      maintained.

PMID- 18612653
TI  - Community structure in ichneumonid parasitoids at different spatial scales.
AB  - The processes underlying parasitoid community structure are little known.
      Stochastic niche-apportionment models provide one route to underlying assemblage
      rules in this and other groups. Previous work has applied this approach to
      parasitoids found on single host species in single populations. However,
      parasitoid communities are known to extend across multiple hosts and scales. The
      patterns of relative abundances generated by five niche-apportionment models were
      compared to those observed in assemblages of two sub-families of the
      Ichneumonidae, the Diplazontinae and Pimplinae, at landscape and patch scales,
      Yorkshire, UK. Three of the five models produced patterns that were significantly
      different to the observed pattern for all taxonomic levels at both spatial
      scales. The Diplazontinae fit the random fraction (RF) model at the landscape
      scale in broadleaved woods. This suggests that hierarchical structuring and
      biotic interactions may play a role in the structuring of Diplazontinae
      assemblages at this scale. In contrast the Pimplinae fit the RF model only at the
      patch scale and only at one site. However, the Pimplini tribe (all chiefly
      parasitoids of Lepidoptera) fit the random assortment (RA) model at both the
      landscape and the patch scales, whilst the Ephialtini tribe (wide range of hosts)
      fit no model at either scale. The ecological interpretation of the RA model
      suggests that the Pimplini tribe is an unsaturated assemblage, where some of the
      total available resources are unused. Our results show, through the fit of
      mechanistic niche-apportionment models, that the processes that may structure
      ichneumonid parasitoid assemblages are not consistent across taxa and spatial
      scales.

PMID- 18612654
TI  - The invasive species Alliaria petiolata (garlic mustard) increases soil nutrient
      availability in northern hardwood-conifer forests.
AB  - The invasion of non-native plants can alter the diversity and activity of soil
      microorganisms and nutrient cycling within forests. We used field studies to
      analyze the impact of a successful invasive groundcover, Alliaria petiolata, on
      fungal diversity, soil nutrient availability, and pH in five northeastern US
      forests. We also used laboratory and greenhouse experiments to test three
      mechanisms by which A. petiolata may alter soil processes: (1) the release of
      volatile, cyanogenic glucosides from plant tissue; (2) the exudation of plant
      secondary compounds from roots; and (3) the decomposition of litter. Fungal
      community composition was significantly different between invaded and uninvaded
      soils at one site. Compared to uninvaded plots, plots invaded by A. petiolata
      were consistently and significantly higher in N, P, Ca and Mg availability, and
      soil pH. In the laboratory, the release of volatile compounds from the leaves of
      A. petiolata did not significantly alter soil N availability. Similarly, in the
      greenhouse, the colonization of native soils by A. petiolata roots did not alter
      soil nutrient cycling, implying that the exudation of secondary compounds has
      little effect on soil processes. In a leaf litter decomposition experiment,
      however, green rosette leaves of A. petiolata significantly increased the rate of
      decomposition of native tree species. The accelerated decomposition of leaf
      litter from native trees in the presence of A. petiolata rosette leaves shows
      that the death of these high-nutrient-content leaves stimulates decomposition to
      a greater extent than any negative effect that secondary compounds may have on
      the activity of the microbes decomposing the native litter. The results presented
      here, integrated with recent related studies, suggest that this invasive plant
      may change soil nutrient availability in such a way as to create a positive
      feedback between site occupancy and continued proliferation.

PMID- 18612655
TI  - Chronic abdominal pain in a patient on chronic peritoneal dialysis: question.

PMID- 18612656
TI  - Chronic abdominal pain in a patient on chronic peritoneal dialysis: answer.

PMID- 18612657
TI  - Renal agenesis and unilateral nephrectomy: what are the risks of living with a
      single kidney?
AB  - The long-term outlook for patients with unilateral renal agenesis or following
      unilateral nephrectomy in childhood is controversial. Animal studies suggest that
      the resultant compensatory increase in glomerular filtration might lead to
      progressive damage to the remaining renal tissue and may generate hypertension.
      Human studies addressing these concerns are limited in number and are difficult
      to interpret because they are small, retrospective, or cross sectional with
      significant variations in duration and completeness of follow-up. The published
      studies suggest that renal function remains stable for several decades in the
      majority of subjects. The clinical significance of mild-grade proteinuria and
      hypertension seen in some patients is unknown. Longitudinal studies are needed to
      understand the long-term effect and significance of the several
      pathophysiological changes observed in the solitary kidney.

PMID- 18612658
TI  - Normative blood pressure data in non-ventilated premature neonates from 28-36
      weeks gestation.
AB  - Blood pressure (BP) measurement in the premature neonate is an essential
      component of neonatal intensive care. Despite significant advances in neonatal
      care, the data available on BP in the premature neonate are limited. The aim of
      this study was to determine normative BP measurements for non-ventilated stable
      premature neonates of gestation age 28-36 weeks in the first month of life using
      an oscillometric method. Neonates born at 28-36 weeks gestation who did not
      require ventilation for >24 h or inotrope support for >24 h were enrolled into
      the study. Blood pressure measurements were taken on days 1, 2, 3, 4, 7, 14, 21
      and 28 where possible prior to discharge. A total of 147 infants were included in
      the study, and 10th and 90th percentiles BPs were obtained for gestation as well
      as birthweight. Changes in BP over time for each gestational week were
      determined. A significant difference in BP from day 1 to day 7 and from day 7 to
      14 was observed in those born at less than 31 weeks gestation, and from day 1 to
      7 in those born at more than 31 weeks gestation, but not from day 14 to 21 and
      from day 21 to 28 for any gestation period. Data on BP for stable non-ventilated
      premature infants using an oscillometric method provide useful information for
      determining hypotension and hypertension in the premature neonate. Premature
      neonates stabilize their BP after 14 days of life, and at this time they have a
      BP similar to that of term infants.

PMID- 18612659
TI  - Predictors of renal scar in children with urinary infection and vesicoureteral
      reflux.
AB  - We evaluated the predictors of renal scar in children with urinary tract
      infections (UTIs) having primary vesicoureteral reflux (VUR). Data of patients
      who were examined by dimercaptosuccinic acid (DMSA) scintigraphy between 1995 and
      2005 were evaluated retrospectively. Gender, age, reflux grade,
      presence/development of scarring, breakthrough UTIs, and resolution of reflux,
      were recorded. The relation of gender, age and VUR grade to preformed scarring
      and the relation of gender, age, VUR grade, presence of preformed scarring,
      number of breakthrough UTIs and reflux resolution to new scarring were assessed.
      There were 138 patients [male/female (M/F) 53/85]. Multivariate analysis showed
      that male gender [odds ratio (OR) 2.5], age > or = 27 months in girls (OR 4.2)
      and grades IV-V reflux (OR 12.4) were independent indicators of renal scarring.
      On the other hand, only the presence of previous renal scarring was found to be
      an independent indicator for the development of new renal scar (OR 13.4). In
      conclusion, while the most predictive variables for the presence of renal
      scarring among children presenting with a UTI were male gender, age > or = 27
      months in girls, and grades IV-V reflux, the best predictor of new scar formation
      was presence of previous renal scarring.

PMID- 18612660
TI  - [Indications and use of benzodiazepines in a palliative care unit].
AB  - BACKGROUND: Benzodiazepines are often used in palliative care for symptom
      control, for example in treatment of dyspnea or anxiety. They are also used for
      palliative sedation, if symptoms are not controlled (fast) enough and a reduction
      of consciousness is therefore necessary. Incidence of palliative sedation has
      been reported to vary between 5-52% of all patients in a palliative care setting
      in several studies. METHOD: Information from the records of 160 patients treated
      in the palliative care unit from September 2003 to December 2004 was evaluated
      from an electronic database. Gender, age, diagnosis, symptoms and medication,
      especially benzodiazepine dosage and application were analyzed. RESULT: Of the
      patients 70% were treated with benzodiazepines but only 3.1% received deep and
      continuous sedation. Benzodiazepines were applied as required in oral or
      sublingual form in 71.8% of all cases. Lorazepam was given most often because of
      anxiety and agitation, oxazepam to induce sleep and midazolam in five cases of
      terminal sedation. Only rarely were diazepam and clonazepam prescribed to prevent
      or resolve convulsions. CONCLUSION: The majority of patients had been treated
      with benzodiazepines whereas only very few had received deep and continuous
      sedation.

PMID- 18612661
TI  - Evaluation of thermal discomfort in Athens territory and its effect on the daily
      number of recorded patients at hospitals' emergency rooms.
AB  - Previous research has shown that temperature and humidity affect human health.
      However, only a few studies have examined the association of a biometeorological
      index, which combines several meteorological parameters and human physiology,
      with health outcomes. The aim of the present study is to assess the thermal
      discomfort in Athens city by using the Predicted Mean Vote (PMV) as well as to
      examine its association with the number of patients recorded at the emergency
      rooms of four main hospitals. Patients were selected based on their diagnosis
      during the summer season (June-August) from 1998 to 2004. Data included hourly
      values of meteorological parameters and daily numbers of patients who visited the
      emergency units of cardiology departments. Poisson regression models were applied
      using generalized estimating equations. A strong negative correlation between
      mean and maximum daily values of PMV and the number of emergency department
      visits was identified. More studies are needed to explore the association of this
      biometeorological index with health outcomes in other regions.

PMID- 18612663
TI  - Regional differences in sweat rate response of steers to short-term heat stress.
AB  - Six Angus steers (319 +/- 8.5 kg) were assigned to one of two groups (hot or cold
      exposure) of three steers each, and placed into two environmental chambers
      initially maintained at 16.5-18.8 degrees C air temperature (Ta). Cold chamber Ta
      was lowered to 8.4 degrees C, while Ta within the hot chamber was increased to
      32.7 degrees C over a 24-h time period. Measurements included respiration rate,
      and air and body (rectal and skin) temperatures. Skin temperature was measured at
      shoulder and rump locations, with determination of sweat rate using a calibrated
      moisture sensor. Rectal temperature did not change in cold or hot chambers.
      However, respiration rate nearly doubled in the heat (P < 0.05), increasing when
      Ta was above 24 degrees C. Skin temperatures at the two locations were highly
      correlated (P < 0.05) with each other and with Ta. In contrast, sweat rate showed
      differences at rump and shoulder sites. Sweat rate of the rump exhibited only a
      small increase with Ta. However, sweat rate at the shoulder increased more than
      four-fold with increasing Ta. Increased sweat rate in this region is supported by
      an earlier report of a higher density of sweat glands in the shoulder compared to
      rump regions. Sweat rate was correlated with several thermal measurements to
      determine the best predictor. Fourth-order polynomial expressions of short-term
      rectal and skin temperature responses to hot and cold exposures produced r values
      of 0.60, 0.84, and 0.98, respectively. These results suggest that thermal inputs
      other than just rectal or skin temperature drive the sweat response in cattle.

PMID- 18612662
TI  - Decreased impacts of the 2003 heat waves on mortality in the Czech Republic: an
      improved response?
AB  - The paper examines impacts on mortality of heat waves in 2003, the hottest summer
      on record in the Czech Republic, and compares them with previous similar events.
      While most summer heat waves over the period since 1986 were associated with
      significantly elevated mortality, this was not the case for three out of the four
      heat waves in 2003. The relatively weak mortality response was particularly
      noteworthy for the most severe heat wave which occurred in the first 10 days of
      August 2003 and resulted in enormous excess mortality in some western European
      countries. A mortality displacement effect and short-term adaptation to heat
      contributed to the reduced mortality impacts of the heat waves that followed
      after previous relatively warm periods. However, the decreased mortality response
      of the 2003 heat waves compared to previous heat waves in the 1990s is also
      likely to have arisen from positive health-care and other socio-economic changes
      in the post-communist central European region over the past decade, as well as a
      better public awareness of heat-related risks due to enhanced media coverage and
      regular biometeorological forecast and warnings.

PMID- 18612664
TI  - Variations in the microbiology of peritonsillar abscess.
AB  - Microbiologic studies are routinely performed in the assessment of peritonsillar
      abscess (PTA). Though the bacterial growth rates of PTA are expected to be
      uniform due to high accessibility and reasonable sterility, they demonstrate a
      vast range of results, which is partially explained by the differing culturing
      methods and incubation times. Our aim was to retrospectively examine the changing
      features identified in the occurrence of PTA bacterial growth rates over a period
      of seven years. A retrospective study was undertaken on all cases of PTA admitted
      from January 1996 to December 2002. Details regarding sex, age and country of
      birth were obtained. Population data and the maximum residue level (MRL) of
      antibiotics in food were collected. Bacteriologic studies were analysed for gram
      stain, aerobic and anaerobic culture results, and also antibiotic sensitivities,
      if obtained. Four hundred and fifty-seven consecutive hospitalisations due to PTA
      were identified; 281 patients who had 310 hospitalisations with known results of
      the microbiologic studies were included. The most common pathogens were
      Streptococcus pyogenes and Prevotella. A statistically significant escalation was
      seen in the anaerobic growth rate from 6.8% of cases in 1996 to 37% in 1999. A
      similar change, though not significant, was noticed with the polymicrobial growth
      rate. None of the parameters investigated showed any statistically significant
      influence on this tendency. These results may clarify the immense range of
      bacterial study results reported, suggest a change in the biologic behaviour of
      the studied bacteria and direct further research.

PMID- 18612665
TI  - Role of immune activation in CD4+ T-cell depletion in HIV-1 infected Indian
      patients.
AB  - OBJECTIVES: The correlation of immune activation with CD4(+) depletion and HIV-1
      disease progression has been evidenced by several studies involving mainly clade
      B virus. However, this needs to be investigated in developing countries such as
      India predominately infected with clade C virus. MATERIALS AND METHODS: In a
      cross-sectional study of 68 antiretroviral treatment naive, HIV-1 infected Indian
      patients, we studied the association between CD4(+) T cells, plasma HIV-1 RNA
      levels, and immune activation markers using unadjusted and adjusted correlative
      analyses. RESULTS: Significant negative correlations of higher magnitude were
      observed between the CD4(+) T cell percentages and plasma HIV-1 RNA levels in the
      study population when adjusted for the effects of immune activation markers.
      However, the negative association of CD4(+) T cells with immune activation
      markers remained unaffected when controlled for the effects of plasma HIV-1 RNA
      levels. CONCLUSIONS: Our results support the important role of immune activation
      in CD4(+) T cell depletion and disease progression during untreated HIV-1
      infection.

PMID- 18612666
TI  - Enterococcus: not an innocent bystander in cirrhotic patients with spontaneous
      bacterial peritonitis.
AB  - Clinicians sometimes experience treatment failure in the initial empirical
      antibiotics treatment using cephalosporins in cirrhotic patients with spontaneous
      bacterial peritonitis (SBP). Enterococcus, which is intrinsically resistant to
      cephalosporins, may be one of the causes of treatment failure. The aim of this
      study was to evaluate the clinical importance and the clinical characteristics of
      spontaneous enterococcal peritonitis (SEP). This was a retrospective cohort study
      of 359 patients with SBP treated in a single tertiary care center in South Korea
      from January 2000 through December 2004. We evaluated the clinical manifestation
      and the treatment results of SBP patients with enterococci identified from
      ascites culture. During the observation period, 13 of 359 patients (3.6%)
      diagnosed with culture-positive SBP had enterococcal peritonitis. For the initial
      empirical treatment, third-generation cephalosporins were administered to the 13
      patients, ten of whom (76.9%) did not improve in the first 48 h. An in vitro
      antibiotic sensitivity test showed that the identified enterococci were
      susceptible to ampicillin plus gentamycin in eight patients (61.5%) and there was
      no vancomycin-resistant enterococcus. Although antibiotics were changed to
      antienterococcal antibiotics in 11 patients, only five patients improved. As a
      result, eight of the 13 patients (61.5%) with enterococcal SBP died during the
      observation period, and the one-month mortality was significantly higher from
      enterococcal SBP than from nonenterococcal SBP (P = 0.038). We conclude that
      enterococcal SBP has poor prognosis and it is reasonable to use antienterococcal
      antibiotics when enterococcus is identified from ascites culture of patients with
      liver cirrhosis.

PMID- 18612668
TI  - Successful control of a hospital-wide vancomycin-resistant Enterococcus faecium
      outbreak in France.
AB  - We describe the control of a hospital-wide vancomycin-resistant Enterococcus
      faecium (VRE) outbreak in a 2,000-bed university hospital located on three
      different sites in Clermont-Ferrand, France. From January 2004 to April 2007, 220
      VRE cases were identified. Overall, 28 different wards had at least one case. All
      of the strains expressed a high level of resistance to vancomycin and to
      teicoplanin carried by the vanA gene. Pulsed-field gel electrophoresis (PFGE)
      analysis of the strains revealed that they were clonally related. Control
      measures consisted of implementing a strategy of VRE screening by rectal swab,
      reinforcing hand hygiene practices and taking contact precautions.
      Recommendations for a restricted use of specific antibiotics were sent to each
      physician. Alcohol-based handrubs were provided throughout the hospital and the
      staff underwent training for their use. Compliance with contact precautions,
      including the use of clean non-sterile gloves and single-use gowns, was
      reinforced. VRE cases were assigned systematically to a single-bed room. In
      October 2007, no new VRE carriage has been detected for 7 months and no clinical
      samples had been VRE-positive for 10 months. In conclusion, a hospital-wide VRE
      outbreak was successfully controlled by a strategy based on routine screening,
      the reinforcement of hand hygiene and taking barrier precautions.

PMID- 18612667
TI  - Low levels of mannose-binding lectin confers protection against tuberculosis in
      Turkish children.
AB  - Mannose-binding lectin (MBL) plays an important role in innate immunity mediating
      phagocytosis and activating the MBL complement pathway. Few studies, conducted in
      adult populations, have shown that genetically determined low MBL levels may
      confer partial protection against tuberculosis (TB). In this study we aimed to
      investigate the relationships between the susceptibility to TB and two low
      producing MBL2 gene polymorphisms (codons 54 and 57) and MBL levels in children.
      Forty-four TB children (27 pulmonary TB, 17 extrapulmonary TB) and 99 age-matched
      healthy control children were included in the study. The mean age in the study
      group was 7.02 +/- 4.5 years. Genotyping of the MBL2 gene for codon 54 and 57
      polymorphisms was carried out, and MBL levels in serum were also detected in all
      subjects from both groups. None of the subjects from either group showed codon 57
      polymorphisms. The frequency of the AB genotype which produces low level MBL is
      significantly lower in the patients (9.1%) compared to control subjects (27.3%)
      (p < 0.011). The difference was especially significant between the extrapulmonary
      group and healthy controls (p < 0.006). The BB genotype was observed in only one
      child from the healthy controls and no children from the patient group. The
      median MBL plasma concentration was also significantly lower in the control group
      than that found in the study group (p = 0.036). These results indicate that low
      levels of MBL and AB genotype may be involved in the protection against
      tuberculosis, especially extrapulmonary tuberculosis in children.

PMID- 18612669
TI  - Modulation of ERG retinal sensitivity parameters with light environment and
      photoperiod.
AB  - It has been reported that the sensitivity to light of the circadian system of
      animals and human subjects can be modulated following long-term exposure to a
      given light environment. Animal studies have also shown that long-term exposure
      to a light regimen, or light history, will have a significant impact on the
      retinal structure and function, the objective of which being to regulate the
      number of photons processed daily by the retina, a phenomenon referred to as
      photostasis. The existence of such a mechanism has never been explored in humans.
      In the present study, daily light exposure was continuously recorded in two
      populations of full-time workers: one group working indoors, in a relatively dim
      environment without access to natural light, and one group working mainly
      outdoors in natural bright light. The effect of seasonal changes in the length of
      the photoperiod was also examined. Retinal sensitivity, as determined with
      scotopic and photopic electroretinograms (ERG), was compared between these two
      groups. Indoor workers received less light than outdoor workers, the difference
      being significant only during work hours. A dim work environment was associated
      with greater retinal sensitivity in scotopic conditions and lower retinal
      sensitivity in photopic conditions when compared to a bright work environment.
      The above differences in retinal sensitivity were evidenced only in workers
      studied during the months with the shortest photoperiod (Fall-Winter). These
      results support the hypothesis that, similar to what was previously demonstrated
      with animal models, the human retina adapts its sensitivity to light according to
      previous chronic light history, suggesting the existence of a photostasis
      phenomenon in the human retina as well.

PMID- 18612670
TI  - Development of automatized new indices for radiological assessment of chest-wall
      deformity and its quantitative evaluation.
AB  - Pre-operative diagnosis of chest-wall deformity is important for successful
      surgical correction and post-operative evaluation of funnel chest patients.
      However, conventional indices that define the severity of deformity have several
      limitations; manually calculated and cannot supply information about asymmetry.
      We developed four indices that can represent both the depression and the
      asymmetry of the chest-wall, and can automatically be extracted by computerized
      image processing technique. Three indices, including eccentricity index (EI),
      flatness index (FI), and circularity index (CI), were suggested to represent the
      depression of the chest-wall, and one index, rotation index (RI), to represent
      the asymmetry of the chest-wall. To verify the feasibility of new indices,
      several synthetic images and real CT images were used to analyze the performance
      of new indices and the statistical relationship with conventional Haller index.
      The experimental results showed possible application of suggested indices to the
      diagnosis of funnel chest patient. Suggested indices showed clear trends of
      change with the severity of chest-wall deformation in regards to both the
      depression and the asymmetry. Results of statistical analysis showed high
      correlation between new indices and HI, showing possibility of replacing HI.

PMID- 18612671
TI  - Passive mechanical properties and constitutive modeling of blood vessels in
      relation to microstructure.
AB  - Mechanical property variations of blood vessels from different anatomical sites
      supposedly reflect variations in microstructure, but no explicit association has
      been afforded so far. The objective of the present study was to provide precise
      histometrical and mechanical data, allowing the identification of such an
      association for arteries and veins. For biomechanical characterization, a one
      dimensional (1D) constitutive model was developed adopting a 'Fung-type'
      exponential function to reproduce the stiffening effect of blood vessels at high
      stresses and combining it with a power function to reproduce the low-stress
      response. Histometrical studies were conducted with quantification of fiber
      composition and waviness for the entire vessel and its layers. Significant
      correlations were found between the model parameters and extracellular matrix
      organization. The novel model associates with recently-derived strain-energy
      functions for the arterial wall, provides powerful fit to uniaxial tension data
      from all types of vascular tissue studied, and conforms explicitly to
      microstructure.

PMID- 18612672
TI  - Multiply methyl-branched fatty acids and diacids in the polar lipids of a
      microaerophilic subsurface microbial community.
AB  - A previously unreported series of di- and tri-methylated fatty acids, as well as
      saturated and monounsaturated diacids were identified in polar lipids isolated
      from environmental subsurface sediment samples. Mechanisms are proposed for their
      formation, but their origin and role in cell membranes remains unknown.

PMID- 18612673
TI  - The GSK-3/beta-catenin-signalling axis in smooth muscle and its relationship with
      remodelling.
AB  - beta-Catenin is a plasma membrane-associated protein that plays a dual role in
      cellular signalling by stabilizing cadherin mediated cell-cell contact and by
      regulating TCF-/LEF-mediated gene transcription. Traditionally, the role of beta
      catenin in health and disease has mainly been studied in the context of
      development and uncontrolled cell growth in diseases such as cancer. Recent
      findings indicate, however, that beta-catenin also plays a significant role in
      fibro-proliferative diseases of several organ systems and that beta-catenin
      regulates mitogenic responses of smooth muscle cells. As several diseases of the
      internal organs are characterized by structural and phenotypic abnormalities of
      smooth muscle, including increased fibro-proliferative responses, these findings
      implicate that beta-catenin could play a broad pathophysiological role. This
      article will review this potential novel role for beta-catenin and associated
      intracellular signalling in smooth muscle and discuss the hypothesis that it
      plays a central role in smooth muscle remodelling.

PMID- 18612675
TI  - Structural relationships among the ribosomal stalk proteins from the three
      domains of life.
AB  - The GTPase center of the large ribosomal subunit, being a landing platform for
      translation factors, and regarded as one of the oldest structures in the
      ribosome, is a universally conserved structure in all domains of life. It is
      thought that this structure could be responsible for the major breakthrough on
      the way to the RNA/protein world, because its appearance would have dramatically
      increased the rate and accuracy of protein synthesis. The major part of this
      center is recognized as a distinct structural entity, called the stalk. The main
      functional part of the stalk in all domains of life is composed of small L12/P
      proteins, which are believed to form an evolutionarily conserved group. However,
      some data indicate that the bacterial and archaeo/eukaryal proteins are not
      related to each other structurally, and only a functional relationship may be
      clearly recognized. To clarify this point, we performed a comprehensive
      comparative analysis of the L12/P proteins from the three domains of life. The
      results show that bacterial and archaeo/eukaryal L12/P-proteins are not
      structurally related and, therefore, might not be linked evolutionarily either.
      Consequently, these proteins should be regarded as analogous rather than
      homologous systems and probably appeared on the ribosomal particle in two
      independent events in the course of evolution.

PMID- 18612676
TI  - Arcus marginalis release in blepharoplasty I: technical facilitation.
AB  - Resection of intraorbital fat compartments in lower-lid blepharoplasty has been
      widely replaced by their realignment over the orbital rim. For older patients
      this usually includes an open subciliary approach with skin resection and
      orbicularis muscle modification. In younger patients this may be done
      transconjunctivally. Fixation of the adipose tissue is controversial. Whereas
      reliance of realignment on spontaneous prolapse may be unpredictable, suture
      fixations may be tedious and even cause scleral show or ectropion. A
      monofilament, double-armed, polypropylene suture on bent straight needles can be
      used safely to transfix the three compartments across maxilla and zygoma. These
      transcutaneous pullout sutures are simply fixed with steri-strips. After only 2
      days the orbital fat will be sufficiently adherent to its new bed.

PMID- 18612679
TI  - Histologic study of the structural changes in fine palpebral skin following
      selective photothermolysis with CO2 laser.
AB  - BACKGROUND: Resurfacing using a CO(2) laser is a modern and efficient mean to
      treat facial wrinkles and aging. It is based on the precise vaporization of the
      most superficial skin layers. This study evaluated the histologic effects of the
      CO(2) laser on palpebral skin. METHODS: Twenty-six patients were selected (22
      females, 4 males). Their age varied from 43 to 72 years and, of these, 19 were
      classified as Fitzpatrick type III and 7 as Fitzpatrick type II. The superior
      palpebral skin was examined before the operation and 3 months, 6 months, 1 year,
      and 2 years after selective photothermolysis. RESULTS: All the postoperative
      evaluations showed consistent dermal and epidermal histologic modifications, with
      the epidermal regeneration showing a normalized anatomy, principally in the
      evaluations made after approximately 1 year. The dermis presents a dramatic
      neocollagenous transformation in the superficial and middle dermis, as well as
      intense modification (restructuring) of the elastic fiber system and reduction in
      the glycosaminoglycans. Both passes of the laser were analyzed and also the
      complete healing process. CONCLUSION: Resurfacing of the fine palpebral skin
      using two passes at 300 and 200 mJ produces an accentuated collagen neoformation
      and correction of the dermal elastosis, in association with a rapid healing
      process.

PMID- 18612674
TI  - The discovery of drugs for obesity, the metabolic effects of leptin and variable
      receptor pharmacology: perspectives from beta3-adrenoceptor agonists.
AB  - Although beta3-adrenoceptor (beta3AR) agonists have not become drugs for the
      treatment of obesity or diabetes, they offer perspectives on obesity drug
      discovery, the physiology of energy expenditure and receptor pharmacology.
      beta3AR agonists, some of which also stimulate other betaARs in humans,
      selectively stimulate fat oxidation in rodents and humans. This appears to be why
      they improve insulin sensitivity and reduce body fat whilst preserving lean body
      mass. Regulatory authorities ask that novel anti-obesity drugs improve insulin
      sensitivity and reduce mainly body fat. Drugs that act on different targets to
      stimulate fat oxidation may also offer these benefits. Stimulation of energy
      expenditure may be easy to detect only when the sympathetic nervous system is
      activated. Leptin resembles beta3AR agonists in that it increases fat oxidation,
      energy expenditure and insulin sensitivity. This is partly because it raises
      sympathetic activity, but it may also promote fat oxidation by directly
      stimulating muscle leptin receptors. The beta1AR and beta2AR can, like the
      beta3AR, display atypical pharmacologies. Moreover, the beta3AR can display
      variable pharmacologies of its own, depending on the radioligand used in binding
      studies or the functional response measured. Studies on the beta3AR demonstrate
      both the difficulties of predicting the in vivo effects of agonist drugs from in
      vitro data and that there may be opportunities for identifying drugs that act at
      a single receptor but have different profiles in vivo.

PMID- 18612680
TI  - Fat reduction using phosphatidylcholine/sodium deoxycholate injections: standard
      of practice.
AB  - The practice of injecting phosphatidylcholine/sodium deoxycholate compounds into
      subcutaneous fat is growing rapidly. As with any new procedure, a standard of
      practice should be developed so that practitioners maintain patient safety as the
      primary goal. Efficacy and predictability of outcome are another priority. As
      injection lipolysis, also known as "lipodissolve," becomes more accepted, many
      standards are being set, such as indications, contraindications, acceptable
      postinjection sequelae, best regions to treat, regions to avoid, and expected
      outcomes. This article establishes a basis of practice for the practitioner
      interested in adding this procedure to his or her repertoire.

PMID- 18612681
TI  - New technique for rectal division in laparoscopic anterior resection--with video.
AB  - BACKGROUND: A new technique for performing laparoscopic anterior resection is
      described. Main differences from the standard technique are (1) pneumoperitoneum
      to improve exposure of the rectum, even in a narrow pelvis; (2) rectal division
      performed using a conventional linear stapler inserted via a 4.5 cm suprapubic
      incision; and (3) eversion of the rectum for tumors close to the anal verge, with
      transection performed under direct vision. METHODS: Results in 78 patients who
      underwent transabdominal transection and in 7 patients requiring rectal eversion
      were compared retrospectively with those in 61 consecutive patients who had
      undergone standard laparoscopic resection. RESULTS: The duration of the operation
      and estimated blood loss were greater with rectal eversion, and more staple
      cartridges were used for the conventional technique; however, the incidence of
      complications was similar for all three groups. Five patients in the conventional
      group required conversion to an open procedure. CONCLUSION: The new technique
      should improve the safety of resection.

PMID- 18612682
TI  - Embolization of the internal iliac artery: cost-effectiveness of two different
      techniques.
AB  - The purpose of this study was to compare the cost-effectiveness of coils versus
      the Amplatzer Vascular Plug (AVP) for occlusion of the internal iliac artery
      (IAA). Between 2002 and January 2006, 13 patients (mean age 73 +/- 13 years) were
      referred for stent-grafting of abdominal aortic aneurysm (n = 6); type I distal
      endoleak (n = 3), isolated iliac aneurysm (n = 3), or rupture of a common iliac
      aneurysm (n = 1). In all patients, extension of the stent-graft was needed
      because the distal neck was absent. Two different techniques were used to occlude
      the IIA: AVP in seven patients (group A) and coil embolization in six patients
      (group C). Immediate results and direct material costs were assessed
      retrospectively. Immediate success was achieved in all patients, and simultaneous
      stent-grafting was successfully performed in two of six patients in group C
      versus five of seven patients in group A. In all group A patients, a single AVP
      was sufficient to achieve occlusion of the IIA, accounting for a mean cost of 485
      euros, whereas in group C patients, an average of 7 +/- 3 coils were used,
      accounting for a mean cost of 1,745 euros. Mean average cost savings using the
      AVP was 1,239 euros. When IIA occlusion is needed, the AVP allows a single-step
      procedure at significant cost savings.

PMID- 18612683
TI  - Cloning of Bacillus licheniformis xylanase gene and characterization of
      recombinant enzyme.
AB  - Hemicellulose is a major component of lignocellulose biomass. Complete
      degradation of this substrate requires several different enzymatic activities,
      including xylanase. We isolated a strain of Bacillus licheniformis from a hot
      springs environment that exhibited xylanase activity. A gene encoding a 23-kDa
      xylanase enzyme, Xyn11, was cloned, and the recombinant protein was expressed in
      an Escherichia coli host and biochemically characterized. The optimum activity of
      the enzyme was at pH 5-7 and 40-50 degrees C. The enzyme was stable at
      temperatures up to 50 degrees C. Against birchwood xylan, the enzyme had an
      apparent K(m) of 6.7 mg/mL and V(max) of 379 micromol/min/mg.

PMID- 18612684
TI  - Toxic effect of inorganic arsenite [As(III)] on metabolic activity of Bacillus
      subtilis by combined methods.
AB  - In this study, microcalorimetry and measurement of culture turbidity were applied
      to evaluate the As(III) toxic effect on the metabolic growth of Bacillus
      subtilis. Using a multichannel thermal activity monitor, the power-time curves of
      the metabolic activity of B. subtilis during growth in the absence and presence
      of various concentrations of As(III) were obtained and studied. The turbidity
      changes during B. subtilis growth with As(III) were investigated by ultraviolet
      visible spectrophotometry and the data agree with the results obtained by
      microcalorimetry. As(III) of various concentrations has different effects on the
      metabolic growth of B. subtilis with biphasic dose-response relationships called
      hormesis [i.e., low-concentration stimulation (10 microg/mL) and high
      concentration inhibition (20-160 microg/mL). Typical J-shapes of the relationship
      between the growth rate constant (k) and c, and toxicity at the half-inhibitory
      concentration (IC(50)) of 98.82 +/- 7.32 microg/mL were obtained. The similarity
      between the two methods corroborates the validity and sensitivity of the
      microcalorimetric technique to investigate the toxic effect of As(III) on
      microorganisms.

PMID- 18612685
TI  - Rapid quantitative detection of Vibrio parahaemolyticus in seafood by MPN-PCR.
AB  - This study aimed to adopt MPN-PCR (most probable number-polymerase chain
      reaction) for rapid detection of the quantity of Vibrio parahaemolyticus in
      seafood. V. parahaemolyticus in seafood could be quantitated by MPN statistics
      according to PCR products. The sensitivity of MPN-PCR was 100 times higher than
      that of direct PCR. Of 225 seafood samples from Qingdao, 165 were positive for
      the presence of V. parahaemolyticus, with an MPN value of >719 per gram, and
      about 41.5% of samples were positive for tdh gene-possessing cells. Eighty muscle
      tissues from the 225 seafood samples were investigated by direct PCR and MPN-PCR,
      but no V. parahaemolyticus was detected. The MPN-PCR test could be completed in
      less than 16 h from the time of sample preparation. It was rapid, sensitive, and
      reliable for comprehensive detection and quick quantitative determination of V.
      parahaemolyticus in seafood and it revealed the potential risk of illness
      associated with their consumption.

PMID- 18612686
TI  - Comparison of 5' noncoding-core with 5' noncoding regions of HCV by RT-PCR:
      importance and clinical implications.
AB  - The molecular detection of HCV RNA by using primers from the 5' noncoding region
      (5'NCR) is universally accepted and preferred for diagnosis; however,
      insufficient sequence variation limits its usefulness for differentiating various
      subtypes-such as 1a/1b and newer subtypes, such as 1c-which cannot be
      distinguished by analysis of this region alone. Determination of genotypes and
      subtypes has important implications in the clinical management and epidemiologic
      investigations. The present study was designed to develop a reverse transcription
      polymerase chain reaction (RT-PCR) assay using degenerate primers from the 5'
      noncoding-core region (5'NCR-core region) for detecting as well as subtyping HCV
      isolates. 5'NCR-core region and 5'NCR were amplified by nested PCR. Genotyping of
      HCV isolates was carried out using restriction fragment length polymorphism
      (RFLP) assay from the 5'NCR-core region using restriction enzymes AccI, MboI, and
      BstNI. The accuracy of the RFLP method was also evaluated using direct
      sequencing.

PMID- 18612687
TI  - Immunomodulatory effects of polar lichens on the function of macrophages in
      vitro.
AB  - Lichen species were collected from King George Island (Antarctica) and were
      screened for their immunomodulatory effect. Among the lichens tested, the
      methanol extract (CR-ME) of Caloplaca regalis showed the highest nitric oxide
      (NO) production in murine peritoneal macrophages. Therefore, this study further
      examined the ability of C. regalis to induce secretory and cellular responses in
      macrophages. Macrophages were treated with various concentrations of CR-ME for 18
      h. The CR-ME treatment induced tumoricidal activity and increased the production
      of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide by macrophages.
      However, CR-ME had a little effect on the levels of reactive oxygen species,
      interleukin-1 and IFN-gamma in CR-ME-treated macrophages. The CR-ME-induced
      tumoricidal activity was partially abrogated by a NO inhibitor and the anti-TNF
      alpha antibody. Thus, the tumoricidal effect of CR-ME appeared to be mainly
      mediated by NO and TNF-alpha production from macrophages. Treating the
      macrophages with a p38 mitogen-activated protein kinase (MAPK) inhibitor
      partially blocked the tumoricidal activation induced by CR-ME, whereas inhibitors
      of the other kinases did not have an inhibitory effect. These results suggest
      that CR-ME induces the tumoricidal activity via the p38 MAPK-dependent pathway.
      Furthermore, electrophoretic mobility shift assay analyses revealed that the CR
      ME treatment induced the activation of the NF-kappaB transcription factor.
      Overall, these results indicate that the tumoricidal activity induced by CR-ME is
      mainly due to TNF-alpha and NO production, and the activation of macrophage by CR
      ME is mediated probably via the p38 MAPK and NF-kappaB pathway. Our results may
      also provide some leads in the development of new immunomodulating drugs.

PMID- 18612688
TI  - Pelvic floor disorders and reconstruction--what next?

PMID- 18612689
TI  - Long-term outlook after successful fibrin glue ablation of cryptoglandular
      transsphincteric fistula-in-ano.
AB  - PURPOSE: Initial success rates for fibrin glue ablation of cryptoglandular
      transsphincteric fistulas have been disappointing. We examined long-term outcomes
      after initially successful fibrin glue ablation of cryptoglandular
      transsphincteric fistulas. METHODS: Retrospective review identified 36 adult
      patients with cryptoglandular transsphincteric fistula Tisseel VH(R) fibrin glue
      ablation that was performed from May 2000 to March 2005. Fibrin glue ablations
      were performed under supervision of fellowship-trained colorectal surgeons.
      Follow-up interval was based on time until recurrence of fistula or time of last
      fistula-free evaluation. RESULTS: Twenty-four men and 12 women patients had a
      mean age of 50 (range, 27-85) years. Twenty patients responded to initial fibrin
      glue ablation treatment. Two additional patients healed with secondary fibrin
      glue ablation. Sixty-six percent (22/33 patients) of cryptoglandular
      transsphincteric fistulas were closed at three months. Eleven patients failed
      fibrin glue ablation at a mean of 33 (range, 6-41) days. Seventeen of 22 short
      term success patients (3 months) were available for long-term follow-up. Ninety
      four percent (16/17 patients) remained healed at final long-term follow-up. The
      remaining patient recurred just before the six-month follow-up. CONCLUSIONS:
      Despite the suboptimal early success rate of fibrin glue ablation for
      cryptoglandular transsphincteric fistulas, when a fistula does close for at least
      six months this appears to be a durable closure. A single patient recurred after
      appearing healed at the three-month check.

PMID- 18612690
TI  - Missense polymorphisms in the adenomatous polyposis coli gene and colorectal
      cancer risk.
AB  - PURPOSE: Whereas truncating germline mutations of the adenomatous polyposis coli
      (APC) gene give rise to familial adenomatous polyposis, missense polymorphisms of
      APC may confer a weaker risk for colorectal cancer. METHODS: We sequenced the
      entire open reading frame of the APC gene and tested for two common MYH mutations
      in a population-based series of patients with colorectal cancer and 5 to 99
      adenomas. Missense adenomatous polyposis coli alterations identified in this
      colorectal cancer multiple-polyp population were analyzed in a population-based
      series of patients with colorectal cancer and healthy control subjects. RESULTS:
      Germline APC or mutY human homologue (MYH) alterations were identified in 16 of
      39 colorectal cancer-multiple polyp patients. Four missense APC gene alterations
      (S130G, E1317Q, D1822V, G2502S) were observed in 13 individuals and 3 additional
      patients carried presumed pathogenic (APC Y94X, biallelic MYH Y165C and
      heterozygous MYH G382D) mutations. When independently assessed in 971 patients
      with colorectal cancer and 954 healthy control subjects, none of the identified
      missense APC alterations conferred a significantly increased risk for colorectal
      cancer, odds ratio (95 percent confidence intervals): S130G = 3.1 (0.29-32.25),
      E1317Q = 1.08 (0.59-2.74), G2502S = 1 (0.65-1.63), D1822V (heterozygous) = 0.79
      (0.64-0.98), D1822V (homozygous) = 0.82 (0.63-1.27). CONCLUSIONS: Germline
      missense APC alterations observed in 33 percent of patients with multiple
      colorectal neoplasms seemed to play a limited role in colorectal cancer risk when
      independently assessed by a population-based, case-control analysis.

PMID- 18612692
TI  - How well are we taking care of melanoma patients in the USA?

PMID- 18612691
TI  - Oviposition cues for a specialist butterfly--plant chemistry and size.
AB  - The oviposition choice of an insect herbivore is based on a complex set of
      stimuli and responses. In this study, we examined the effect of plant secondary
      chemistry (the iridoid glycosides aucubin and catalpol) and aspects of size of
      the plant Plantago lanceolata, on the oviposition behavior of the specialist
      butterfly Melitaea cinxia. Iridoid glycosides are known to deter feeding or
      decrease the growth rate of generalist insect herbivores, but can act as
      oviposition cues and feeding stimulants for specialized herbivores. In a previous
      observational study of M. cinxia in the field, oviposition was associated with
      high levels of aucubin. However, this association could have been the cause
      (butterfly choice) or consequence (plant induction) of oviposition. We conducted
      a set of dual- and multiple-choice experiments in cages and in the field. In the
      cages, we found a positive association between the pre-oviposition level of
      aucubin and the number of ovipositions. The association reflects the butterfly
      oviposition selection rather than plant induction that follows oviposition. Our
      results also suggest a threshold concentration below which females do not
      distinguish between levels of iridoid glycosides. In the field, the size of the
      plant appeared to be a more important stimulus than iridoid glycoside content,
      with bigger plants receiving more oviposition than smaller plants, regardless of
      their secondary chemistry. Our results illustrate that the rank of a cue used for
      oviposition may be dependent on environmental context.

PMID- 18612693
TI  - Prognostic relevance of Tensin4 expression in human gastric cancer.
AB  - BACKGROUND: The Tensin4 gene is involved in various biological events by
      mediating signal transduction. This study was designed to clarify its clinical
      significance in gastric cancer. METHODS: A total of 114 gastric cancer patients
      were enrolled in this study, and we obtained paired samples from tumor tissue and
      matched normal mucosa. Total RNA was extracted, and TNS4 mRNA expression was
      quantified using real-time reverse-transcription polymerase chain reaction. TNS4
      protein expression was investigated by immunohistochemistry. Additionally, the
      relationship between TNS4 expression and clinicopathologic factors was
      statistically analyzed. RESULTS: TNS4 mRNA expression was significantly higher in
      tumor tissue than in normal mucosa (p < 0.0001). Additional immunohistochemical
      analysis demonstrated that TNS4 protein was predominantly expressed in gastric
      cancer. Tumors with higher TNS4 mRNA expression showed histologically poorer
      grade (p < 0.02), deeper invasion into the serosa (p < 0.01), more positive lymph
      node metastasis (p < 0.02) or peritoneal dissemination (p < 0.05). Patients with
      high TNS4 mRNA expression tumor were more likely to have cancer-related death (p
      < 0.05). A Kaplan-Meier curve also demonstrated that patients with high TNS4
      expression tumor had significantly poorer prognosis (p < 0.01) than those with
      low TNS4 expression tumor. In particular, the 2-year overall survival rates were
      48.2% and 83.1%, respectively, a very significant difference. Multivariate
      analysis revealed that high TNS4 mRNA expression was an independent prognostic
      predictor (relative risk 1.41, 95% confidence interval 1.03-1.96, p = 0.03).
      CONCLUSION: TNS4 was frequently overexpressed in gastric cancer, and tumors with
      high TNS4 mRNA expression showed biologically aggressive behavior. High TNS4 mRNA
      expression may be a novel prognostic predictor for those patients.

PMID- 18612694
TI  - SnoN overexpression is predictive of poor survival in patients with esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Earlier studies have identified the minimal overlapping region of
      amplification at 3q26 in esophageal squamous cell carcinoma (ESCC) by comparative
      genomic hybridization (CGH) analysis. These include PIK3CA which encodes the
      p110alpha catalytic subunit of phosphatidylinositol (PI) 3-kinase, a telomerase
      RNA component (TERC), a squamous cell carcinoma-related oncogene (SCCRO),
      ecotropic viral integration site-1 (EVI-1), and a Ski-related novel oncogene
      (SnoN). In the present study, we investigated the mRNA levels of four candidate
      genes (TERC, SCCRO, EVI-1, and SnoN) to determine whether genes other than PIK3CA
      are targets for amplification at 3q26 in ESCC. And also, we examined SnoN
      expression in ESCC samples. METHODS: Fifty-nine representative cases with ESCC
      were selected from our archives. We performed quantitative RT-PCR of four
      candidate genes (TERC, SCCRO, EVI-1, and SnoN) and immunohistochemistry for SnoN.
      Finally, we correlated these findings with the clinicopathological
      characteristics to determine their interrelationship. RESULTS: Among the four
      genes we tested, only SnoN mRNA was consistently overexpressed in primary ESCC,
      compared with those in corresponding nontumorous esophageal epithelia (P <
      0.001). Immunoreactive SnoN was detectable in 31 of 59 (52.5%) esophageal
      squamous cell carcinoma specimens. The levels of SnoN expression were found to
      correlate with the depth of invasion and recurrence (P < 0.05). Furthermore,
      patients with positive staining for SnoN displayed more unfavorable outcomes than
      patients with negative staining (P < 0.05). CONCLUSION: SnoN is likely to be the
      target of the amplification at 3q26 in ESCC and plays an important role in the
      development of ESCC, influencing disease-specific survival.

PMID- 18612696
TI  - Human genetic and structural genomic variation: would genome-wide association
      studies be the solution for cancer complexity like Alexander the Great for the
      "Gordian Knot"?

PMID- 18612697
TI  - Central cervical nodal metastasis from papillary thyroid microcarcinoma: pattern
      and factors predictive of nodal metastasis.
AB  - BACKGROUND: Although several factors are thought to predict the occurrence of
      lymph node metastases from papillary thyroid microcarcinoma (PTMC), the pattern
      of nodal metastasis has been rarely studied. We evaluated the pattern and factors
      predictive of central cervical metastasis from PTMC. METHODS: Seventy-two
      patients with PTMC underwent total thyroidectomy and central neck dissection,
      including three who underwent therapeutic modified radical neck dissection. Lymph
      node involvement was analyzed by neck subsite, and clinicopathologic variables
      predictive of nodal metastasis were determined. RESULTS: Central and lateral
      nodal metastases were found in 29 (40.3%) and 3 (4.2%) patients, respectively,
      and ipsilateral paratracheal, pretracheal, superior mediastinal, and
      contralateral paratracheal lymph node metastases in 27 (37.5%), 8 (11.1%), 4
      (5.6%), and 1 (1.4%), respectively. Sex, age, tumor size, multifocality,
      bilaterality, extracapsular invasion, lymphovascular invasion, and MACIS
      (metastases, age, completeness of resection, invasion, size) for central node
      metastasis were not predictive of metastasis (P > .1). Temporary and permanent
      hypocalcemia was observed in 17 (23.6%) and 1 (1.4%) patients, respectively, and
      transient vocal fold paralysis in 1 (1.4%). CONCLUSION: Despite the absence of
      palpable neck nodes, PTMC is associated with a high rate of central lymph node
      metastasis to ipsilateral and pretracheal subsites. No clinicopathologic factor
      predicted nodal metastasis. In patients with PTMC involving one lobe and positive
      nodes, neck dissection may exclude the contralateral side.

PMID- 18612699
TI  - Scoring systems: are they ideal?

PMID- 18612695
TI  - Extra-intestinal manifestations of familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited
      disorder, which results from a germ line mutation in the APC (adenomatous
      polyposis coli) gene. FAP is characterized by the formation of hundreds to
      thousands of colorectal adenomatous polyps. Although the development of
      colorectal cancer stands out as the most prevalent complication, FAP is a
      multisystem disorder of growth. This means, it is comparable to other diseases
      such as the MEN syndromes, Von Hippel-Lindau disease and neurofibromatosis.
      However, the incidence of many of its clinical features is much lower. Therefore,
      a specialized multidisciplinary approach to optimize health care-common for other
      disorders-is not usually taken for FAP patients. Thus, clinicians that care for
      and counsel members of high-risk families should have familiarity with all the
      extra-intestinal manifestations of this syndrome. FAP-related complications, for
      which medical attention is essential, are not rare and their estimated lifetime
      risk presumably exceeds 30%. Affected individuals can develop thyroid and
      pancreatic cancer, hepatoblastomas, CNS tumors (especially medulloblastomas), and
      various benign tumors such as adrenal adenomas, osteomas, desmoid tumors and
      dental abnormalities. Due to improved longevity, as a result of better prevention
      of colorectal cancer, the risk of these clinical problems will further increase.
      We present a clinical overview of extra-intestinal manifestations, including
      management and treatment options for the FAP syndrome. Furthermore, we provide
      recommendations for surveillance of FAP complications based on available
      literature.

PMID- 18612700
TI  - Getting chemotherapy into the cancerous tissue.

PMID- 18612701
TI  - Molecular phenotyping of thyroid tumors identifies a marker panel for
      differentiated thyroid cancer diagnosis.
AB  - BACKGROUND: Currently, a large proportion of individuals undergo thyroidectomy as
      a diagnostic procedure for cancer. The objective of this work was to evaluate the
      molecular phenotype of differentiated thyroid cancer (DTC) and benign thyroid
      lesions to identify molecular markers that allow for accurate thyroid cancer
      diagnosis. METHODS: Tissue microarrays consisting of 100 benign and 105 malignant
      thyroid lesions, plus 24 lymph node samples, were stained for a panel of 57
      molecular markers. Significant associations between marker staining and tumor
      pathology (DTC versus benign) were determined using contingency table and Mann
      Whitney U (MU) tests. A Random Forests classifier algorithm was also used to
      identify useful/important molecular classifiers. RESULTS: Of the 57 diagnostic
      markers evaluated 35 (61%) were significantly associated with a DTC diagnosis
      after multiple testing correction. Of these, in DTC compared with benign thyroid
      tumors, 8 markers were downregulated and 27 upregulated. The most significant
      markers for DTC diagnosis were: Galectin-3, Cytokeratin 19, Vascular Endothelial
      Growth Factor, Androgen Receptor, p16, Aurora-A, and HBME-1. Using the entire
      molecular marker panel, a Random Forests algorithm was able to classify tumors as
      DTC or benign with an estimated sensitivity of 87.9%, specificity of 94.0%, and
      an accuracy of 91.0%. CONCLUSION: Evaluation of the DTC and benign thyroid tumor
      molecular phenotype has allowed for identification of a marker panel, composed of
      both established and novel markers, useful for thyroid cancer diagnosis. These
      results suggest that further study of the molecular profile of thyroid tumors is
      warranted, and a diagnostic molecular marker panel may potentially improve
      patient selection for thyroid surgery.

PMID- 18612702
TI  - Ablation of high intensity focused ultrasound combined with SonoVue on rabbit VX2
      liver tumors: assessment with conventional gray-scale US, conventional
      color/power Doppler US, contrast-enhanced color Doppler US, and contrast-enhanced
      pulse-inversion harmonic US.
AB  - BACKGROUND: We investigated effects of high intensity focused ultrasound (HIFU)
      combined with contrast agent SonoVue on rabbit VX2 liver tumors by using
      conventional gray-scale ultrasonography (US), color/power Doppler (CD/PD) US,
      contrast-enhanced color Doppler (CE CD) US, and contrast-enhanced pulse-inversion
      harmonic (CE PIH) US. METHODS: Fourteen days after implantation of VX2 tumors in
      livers of 50 rabbits, animals were randomly separated into two groups. Based on
      principles of HIFU, the volume of the tumor was divided into several parallel
      "planes" to be ablated. Before ablation on each "plane," 0.2 mL SonoVue was
      injected in bolus via ear veins of rabbits in group II and normal saline solution
      was administrated in group I. Conventional gray-scale US, CD US, PD US, CE CD US,
      and CE PIH US were performed before and after ablation. RESULTS: Twenty-three
      surviving rabbits in each group underwent HIFU ablation. Conventional gray-scale
      US showed ablated areas diffusely hyperechoic. On CE PIH US, coagulated areas
      presented perfusion defect. Both conventional gray-scale US and CE PIH US showed
      the ablated volume in group II was larger than that in group I. CD US and PD US
      demonstrated residual vessels in periphery ablated areas in group I, but no
      residual vessels in group II. CE CD US and CE PIH US depicted less residual
      vessels in periphery ablated areas in group II than that in group I. CONCLUSION:
      By enlarging ablated volume of tissue and reducing residual vessels, effects of
      HIFU ablation on rabbit VX2 liver tumors were enhanced by contrast agent SonoVue.

PMID- 18612703
TI  - Adjuvant therapy for adenocarcinoma of the pancreas: analysis of reported trials
      and recommendations for future progress.
AB  - The delivery of postoperative combined modality adjuvant therapy for completely
      resected pancreatic cancer was initially shown to be beneficial on the basis of a
      prospective, randomized trial published in 1985. Since then, oncologists have
      debated whether chemotherapy, chemoradiation, or both is optimal adjuvant therapy
      after pancreatectomy for ductal adenocarcinoma of the pancreas; no global
      consensus has emerged. Unfortunately, despite the completion of a number of
      subsequent randomized trials of adjuvant therapy since 1985, no further
      improvements in overall survival have materialized. This lack of progress is not
      simply the result of ineffective systemic therapies, but in part the result of
      poor trial design and calls for a more disciplined approach to the selection of
      patients for surgery, pathologic assessment of surgical resection margins, and
      postoperative (pretreatment) imaging. This is the only way to ensure that
      patients who receive adjuvant therapy are actually receiving therapy for
      radiographically occult possible microscopic disease, rather than therapy for
      incompletely resected locally advanced disease or early postoperative metastases.
      A critical analysis of completed adjuvant trials will be provided and a framework
      for the conduct of future trials of adjuvant therapy proposed.

PMID- 18612704
TI  - Relationship between provider volume and outcomes for orthotopic liver
      transplantation.
AB  - INTRODUCTION: Recent data suggests that the previously demonstrable relationship
      between hospital volume and outcomes for liver transplant procedures may no
      longer exist. Furthermore, to our knowledge, no study has been published
      examining whether individual surgeon volume is associated with outcomes in liver
      transplantation. MATERIALS AND METHODS: The Nationwide Inpatient Sample database
      was used to obtain early clinical outcome and resource utilization data for liver
      transplant procedures performed in the USA from 1988 through 2003. The
      relationship between surgeon and hospital volume and early clinical outcomes was
      analyzed with and without adjustment for certain confounding variables such as
      patient age and presence of co-morbid disease. RESULTS: The in-hospital mortality
      rate, major postoperative complication rate, and length of hospital stay after
      liver transplantation did not differ significantly based on hospital procedural
      volume. These outcome variables did, however, exhibit a statistically significant
      inverse relationship with individual surgeon volume of liver transplant
      procedures. A significant relationship between procedure volume and outcomes for
      liver transplantation cannot be demonstrated at the level of transplant center,
      but does appear to exist at the level of the individual transplant center.
      CONCLUSION: Minimal volume requirements for individual liver transplant surgeons
      may be justified, pending validation of this volume-outcomes relationship using a
      clinical data source.

PMID- 18612705
TI  - Prospective assessment of patient selection for antireflux surgery by combined
      multichannel intraluminal impedance pH monitoring.
AB  - INTRODUCTION: Selecting gastroesophageal reflux disease (GERD) patients for
      surgery on the basis of standard 24-h pH monitoring may be challenging,
      particularly if this investigation does not correlate with clinical symptoms.
      Combined multichannel intraluminal impedance pH monitoring (MII-pH) is able to
      physically detect each episode of intraesophageal bolus movements, enabling
      identification of either acid or non-acid reflux episodes and thus establish the
      association of the reflux with symptoms. MATERIALS AND METHODS: We prospectively
      assessed and reviewed data from 314 consecutive patients who underwent MII-pH for
      GERD not responsive or not compliant to proton pump inhibitor therapy. One
      hundred fifty-three patients with a minimum follow-up of 1 year constituted the
      study population. Clinical outcomes and satisfaction rate were collected in all
      patients who underwent laparoscopic Nissen-Rossetti fundoplication. Outcomes were
      reported for patients with normal and ineffective peristalsis and for patients
      with positive pH monitoring, negative pH monitoring and positive total number of
      reflux episodes at MII, and negative pH monitoring and normal number of reflux
      episodes at MII and a positive symptom index correlation with MII. RESULTS: The
      overall patient satisfaction rate was 98.3%. No differences were recorded in the
      clinical outcomes of the patients with preoperative normal and ineffective
      peristalsis. No differences in patients' satisfaction and clinical postoperative
      DeMeester symptom scoring system were noted between the groups as determined by
      MII-pH. CONCLUSION: MII-pH provides useful information for objective selection of
      patients to antireflux surgery. Nissen fundoplication provides excellent outcomes
      in patients with positive and negative pH and positive MII monitoring or Symptom
      Index association. More extensive studies are needed to definitively standardize
      the useful MII-pH parameters to select the patient to antireflux surgery.

PMID- 18612707
TI  - Gastrectomy and lymphadenectomy for gastric cancer: is the pancreas safe?
AB  - INTRODUCTION: Resection of the capsule of the pancreas is part of the radical
      operation proposed by oriental authors for the treatment of gastric cancer. It is
      unclear; however, if resection of the capsule is a safe procedure or even if it
      is necessary. This study aims to assess in patients treated for gastric cancer
      the occurrence of: (a) pancreatic fistula and (b) metastasis to the pancreatic
      capsule. METHODS: We studied 80 patients (mean age 61 years, 42 males) submitted
      to gastrectomy with resection of the pancreatic capsule by hydrodissection.
      Patients with pancreatic disease, tumoral invasion of the pancreas, submitted to
      concomitant splenectomy, or anastomotic leakage were excluded. The tumor was
      located in the distal third of the stomach in 60% of the patients, in the middle
      third in 27%, and proximally in 12%. Total gastrectomy was performed in 27% of
      the cases and partial gastrectomy in 73%. In all patients, amylase activity in
      the drainage fluid was measured on day 2. If initial measurement was abnormal,
      subsequent measurements were performed in alternated days until normalization.
      Pancreatic fistula was defined as amylase levels greater than 600. In 25 of these
      patients (mean age 53 years, 16 males), the pancreatic capsule was histologically
      analyzed for metastasis. RESULTS: Pancreatic fistula was diagnosed in eight (10%)
      patients. The mean amylase level was 5,863. Normalization of amylase levels was
      achieved within 7 days in all patients. No patient developed clinical signs of
      fistula besides abnormal amylase levels in the drainage fluid, such as intra
      abdominal abscesses. Pancreatic fistula was associated to younger age (p = 0.03)
      but not to gender (p = 0.1), tumor location (p = 0.6), and type of gastrectomy (p
      = 0.8). Metastasis to the pancreatic capsule was not identified. CONCLUSION: In
      conclusion, resection of the pancreatic capsule must be discouraged due to
      subclinical pancreatic fistula in a significant number of the cases and absence
      of metastasis.

PMID- 18612706
TI  - The effects of vasopressors on perfusion of gastric graft after esophagectomy. An
      experimental study.
AB  - AIMS: To evaluate the impact of the perioperative administration of
      norepinephrine on the perfusion of the esophageal graft. METHODS: This is an
      experimental study. Six swine underwent transhiatal esophagectomy; the stomach
      was used to replace the resected esophagus. We provoked hemorrhagic shock to the
      animals and then we administered noradrenaline to restore the blood pressure. We
      monitored the graft perfusion perioperatively using the technique of
      microdialysis. RESULTS: In all animals, the graft experienced severe
      hypoperfusion after the administration of noradrenaline that was statistically
      significant. CONCLUSIONS: Our data support the hypothesis that norepinephrine
      should be used with extreme caution in the perioperative setting after
      esophagectomy. Further studies, however, will be required to evaluate the
      clinical significance of this finding.

PMID- 18612708
TI  - Behavior of the infection by Helicobacter pylori of the gastric remnant after
      subtotal gastrectomy and Roux-en-Y anastomosis for benign diseases.
AB  - INTRODUCTION: Reinfection by Helicobacter pylori of the gastric remnant after
      partial gastrectomy has been implicated in the development of gastric cancer at
      the gastric stump. OBJECTIVE: The aim of this study is to determine the rate of
      infection by H. pylori after partial gastrectomy and Roux-en-Y anastomosis for
      benign disease. MATERIALS AND METHODS: A total of 79 patients with long segment
      Barrett's esophagus were submitted to vagotomy, anti-reflux surgery, two thirds
      distal gastrectomy, and Roux-en-Y anastomosis 70 cm long. In all preoperative
      biopsy samples were taken from the antrum. After surgery, four endoscopic studies
      were performed in different periods of time. Mean follow-up was 98 months after
      operation (60-240). RESULTS: Three groups of patients were identified: (a) group
      1, 43 patients (54%) who had no preoperative infection by H. pylori and remained
      so late after surgery; (b) group 2, 21 patients (27%) who had no preoperative
      infection by H. pylori but presented infection of the gastric remnant that
      increased parallel to the length of follow-up; (c) group 3, 15 patients (19%) who
      presented infection by H. pylori before surgery. From them, 11 showed reinfection
      of the gastric remnant, while four patients had no reinfection. CONCLUSION: After
      partial gastrectomy and Roux-en-Y anastomosis for benign disease, there are three
      different patterns of behavior regarding reinfection or not by H. pylori. A total
      of 41% of patients presented H. pylori reinfection at the gastric remnant after
      Roux-en-Y anastomosis, which increased parallel to the length of follow-up.

PMID- 18612709
TI  - Clostridium difficile infection: a surgical disease in evolution.
AB  - INTRODUCTION: Several recent publications suggest an increase in the incidence of
      Clostridium difficile colitis. However, such studies commonly lack denominators
      over which to index this rise. There is also concern in the literature that
      disease virulence is increasing. METHODS: Billing, admission, operative, and
      infection databases at a single tertiary care center identified patients admitted
      from 1990 to 2006 with a diagnosis of C. difficile infection. Grouped by era,
      case numbers were indexed against overall hospital, operative, and laboratory
      volumes. C. difficile colectomy cases were individually examined and analyzed.
      RESULTS: The number of hospitalized patients diagnosed with C. difficile colitis
      increased in a linear fashion during the study period (1990, 14 cases; 2006, 927
      cases). The colectomy per C. difficile case ratio did not change over the study
      period (era 1, 0.17%; era 2, 0.20%; era 3, 0.16%). Thirteen patients underwent
      colectomy with 54% surviving. The increase in patients admitted with a diagnosis
      of C. difficile was significantly associated with hospital volume (p = 0.04),
      operative volume (p < 0.001), and lab testing volume (p = 0.008). CONCLUSION: The
      number of C. difficile patients admitted to our hospital is rising at an alarming
      rate. This reflects national trends and urgent action seems warranted to prevent
      a C. difficile epidemic.

PMID- 18612710
TI  - Surgical specialization and operative mortality in hepato-pancreatico-biliary
      (HPB) surgery.
AB  - INTRODUCTION: Surgeon specialization has been shown to result in improved
      outcomes but may not be the sole measure of surgical quality in hepato
      pancreatico-biliary (HPB) surgery. We attempted to determine which factors
      predominate in optimal patient outcomes between volume, surgeon, and hospital
      resources. METHODS: All non-transplant pancreatic (n = 7195) and liver operations
      (n = 4809) from the Nationwide Inpatient Sample (NIS) were examined from 1998
      2005. Surgeons and hospitals were divided into two groups, transplant (TX) or non
      transplant (non-TX), using the unique surgeon and hospital identifier of NIS. A
      logistic regression model examined the relationship between factors while
      accounting for patient and hospital factors. RESULTS: We identified 4,355 primary
      surgeons (165 TX, 4,190 non-TX) who performed HPB surgery in 675 hospitals across
      12 different states. Non-TX surgeons performed the majority of pancreatic (97%)
      and liver procedures (81%). There was no difference in mortality after HPB
      surgery depending on surgeon specialty (p = 0.59). Factors for inpatient death
      after HPB surgery included increasing age, male gender, and public insurance (p <
      0.05). In addition, surgery performed at a TX center had a 21% lower odds of
      perioperative mortality. DISCUSSION: Non-TX surgeons performed the majority of
      pancreatic and liver surgery in the US. Hospital factors like support of
      transplantation but not surgical specialty, appeared to impact operative
      mortality. Future regulatory benchmarks should consider these types of center
      based facilities and resources to assess patient outcomes.

PMID- 18612711
TI  - The practice of traditional bonesetting: training algorithm.
AB  - Traditional bonesetters (TBS) have been in Nigeria for centuries. Up to 85% of
      patients with fractures present first to the traditional bonesetters before
      coming to the hospital and therefore this mode of care delivery cannot be
      overlooked in Nigeria. We attempted to document the current practice of TBS in
      Ibadan and their methods of fracture treatment with a view to training and
      improving the services offered by them. We carried out a literature search to
      review all previous studies on traditional bonesetters' practice and visited a
      few of them to document their current practice. The only change in the management
      of fractures by the TBS over the past 28 years was the use of spiritual methods
      of healing to treat open comminuted fractures; a technique for which no
      scientific basis was readily discernible. There is a need to educate and train
      the TBS in effective management of both open and closed fractures. Such training
      should be provided by orthodox orthopedic surgeons with a view to minimizing
      mismanagement of fractures. To this end, we propose a training algorithm.

PMID- 18612712
TI  - S100A6 expression and function in human osteosarcoma.
AB  - There is a critical need to identify markers that can accurately identify
      existing or predict future metastatic disease in patients with osteosarcoma since
      the majority of patients present with undetectable micrometastatic disease. We
      previously reported S100A6 is overexpressed in human osteosarcoma and increased
      expression of S100A6 by immunohistochemistry correlated with decreased clinical
      metastasis. We have established 11 primary cultures from biopsies of patients
      with osteosarcoma and ten of the 11 primary cultures have increased expression of
      S100A6 relative to normal human osteoblasts. To further explore possible
      mechanisms for metastasis suppression previously reported, we used in this report
      siRNA-mediated knockdown of S100A6 in four commonly used human osteosarcoma
      lines, then examined their cell adhesion, migration, and invasion properties.
      Knockdown of S100A6 expression inhibited cell adhesion and promoted cell
      migration and invasion in these lines. Conversely, S100A6 overexpression enhanced
      cell adhesion and inhibited cell invasion. Our data demonstrate S100A6 is
      commonly overexpressed in human osteosarcoma. S100A6 may inhibit osteosarcoma
      metastasis by promoting cell adhesion and inhibiting cell motility and invasion.
      Thus, S100A6 may be considered a potential marker for human osteosarcoma with
      prognostic value for identifying patients without metastases.

PMID- 18612713
TI  - Hormonal regulation of cerebellar development and plasticity.
AB  - Cerebellar development and plasticity is involved in various epigenetic processes
      that activate specific genes at different time point. The epigenetic influences
      include humoral influences from endocrine cells of peripheral organs. A number of
      hormone receptors are expressed in cerebellum, and cerebellar function is greatly
      influenced by hormonal status. Furthermore, recent studies have shown that some
      of such substances are produced locally and affect through their specific hormone
      receptors. The aim of this special issue was to introduce several key features of
      hormones and their receptors to regulate cerebellar development and plasticity.
      The contribution covers thyroid/steroid hormone systems including orphan
      receptors and co-regulators, neurosteroids, and transporters. It also covers
      environmental signal that may affect cerebellar hormonal environment.
      Furthermore, several neuropeptides, which are initially found as neuroendocrine
      hormones but later identified as neurotransmitters that play an important role in
      cerebellar function, are also covered.

PMID- 18612714
TI  - Navigating the JGIM Special Issue on Medical Education.

PMID- 18612715
TI  - Predictive validity evidence for medical education research study quality
      instrument scores: quality of submissions to JGIM's Medical Education Special
      Issue.
AB  - BACKGROUND: Deficiencies in medical education research quality are widely
      acknowledged. Content, internal structure, and criterion validity evidence
      support the use of the Medical Education Research Study Quality Instrument
      (MERSQI) to measure education research quality, but predictive validity evidence
      has not been explored. OBJECTIVE: To describe the quality of manuscripts
      submitted to the 2008 Journal of General Internal Medicine (JGIM) medical
      education issue and determine whether MERSQI scores predict editorial decisions.
      DESIGN AND PARTICIPANTS: Cross-sectional study of original, quantitative research
      studies submitted for publication. MEASUREMENTS: Study quality measured by MERSQI
      scores (possible range 5-18). RESULTS: Of 131 submitted manuscripts, 100 met
      inclusion criteria. The mean (SD) total MERSQI score was 9.6 (2.6), range 5-15.5.
      Most studies used single-group cross-sectional (54%) or pre-post designs (32%),
      were conducted at one institution (78%), and reported satisfaction or opinion
      outcomes (56%). Few (36%) reported validity evidence for evaluation instruments.
      A one-point increase in MERSQI score was associated with editorial decisions to
      send manuscripts for peer review versus reject without review (OR 1.31, 95%CI
      1.07-1.61, p = 0.009) and to invite revisions after review versus reject after
      review (OR 1.29, 95%CI 1.05-1.58, p = 0.02). MERSQI scores predicted final
      acceptance versus rejection (OR 1.32; 95% CI 1.10-1.58, p = 0.003). The mean
      total MERSQI score of accepted manuscripts was significantly higher than rejected
      manuscripts (10.7 [2.5] versus 9.0 [2.4], p = 0.003). CONCLUSIONS: MERSQI scores
      predicted editorial decisions and identified areas of methodological strengths
      and weaknesses in submitted manuscripts. Researchers, reviewers, and editors
      might use this instrument as a measure of methodological quality.

PMID- 18612716
TI  - Proposed standards for medical education submissions to the Journal of General
      Internal Medicine.
AB  - To help authors design rigorous studies and prepare clear and informative
      manuscripts, improve the transparency of editorial decisions, and raise the bar
      on educational scholarship, the Deputy Editors of the Journal of General Internal
      Medicine articulate standards for medical education submissions to the Journal.
      General standards include: (1) quality questions, (2) quality methods to match
      the questions, (3) insightful interpretation of findings, (4) transparent,
      unbiased reporting, and (5) attention to human subjects' protection and ethical
      research conduct. Additional standards for specific study types are described. We
      hope these proposed standards will generate discussion that will foster their
      continued evolution.

PMID- 18612717
TI  - Variation in internal medicine residency clinic practices: assessing practice
      environments and quality of care.
AB  - BACKGROUND: Few studies have systematically and rigorously examined the quality
      of care provided in educational practice sites. OBJECTIVE: The objectives of this
      study were to (1) describe the patient population cared for by trainees in
      internal medicine residency clinics; (2) assess the quality of preventive
      cardiology care provided to these patients; (3) characterize the practice-based
      systems that currently exist in internal medicine residency clinics; and (4)
      examine the relationships between quality, practice-based systems, and features
      of the program: size, type of program, and presence of an electronic medical
      record. DESIGN: This is a cross-sectional observational study. SETTING: This
      study was conducted in 15 Internal Medicine residency programs (23 sites)
      throughout the USA. PARTICIPANTS: The participants included site champions at
      residency programs and 709 residents. MEASUREMENTS: Abstracted charts provided
      data about patient demographics, coronary heart disease risk factors, processes
      of care, and clinical outcomes. Patients completed surveys regarding
      satisfaction. Site teams completed a practice systems survey. RESULTS: Chart
      abstraction of 4,783 patients showed substantial variability across sites. On
      average, patients had between 3 and 4 of the 9 potential risk factors for
      coronary heart disease, and approximately 21% had at least 1 important barrier of
      care. Patients received an average of 57% (range, 30-77%) of the appropriate
      interventions. Reported satisfaction with care was high. Sites with an electronic
      medical record showed better overall information management (81% vs 27%) and
      better modes of communication (79% vs 43%). CONCLUSIONS: This study has provided
      insight into the current state of practice in residency sites including aspects
      of the practice environment and quality of preventive cardiology care delivered.
      Substantial heterogeneity among the training sites exists. Continuous measurement
      of the quality of care provided and a better understanding of the training
      environment in which this care is delivered are important goals for delivering
      high quality patient care.

PMID- 18612718
TI  - The ambulatory long-block: an accreditation council for graduate medical
      education (ACGME) educational innovations project (EIP).
AB  - INTRODUCTION: Historical bias toward service-oriented inpatient graduate medical
      education experiences has hindered both resident education and care of patients
      in the ambulatory setting. AIM: Describe and evaluate a residency redesign
      intended to improve the ambulatory experience for residents and patients.
      SETTING: Categorical Internal Medicine resident ambulatory practice at the
      University of Cincinnati Academic Health Center. PROGRAM DESCRIPTION: We created
      a year-long continuous ambulatory group-practice experience separated from
      traditional inpatient responsibilities called the long block as an Accreditation
      Council for Graduate Medical Education Educational Innovations Project. The
      practice adopted the Chronic Care Model and residents received extensive
      instruction in quality improvement and interprofessional teams. PROGRAM
      EVALUATION: The long block was associated with significant increases in resident
      and patient satisfaction as well as improvement in multiple quality process and
      outcome measures. Continuity and no-show rates also improved. DISCUSSION: An
      ambulatory long block can be associated with improvements in resident and patient
      satisfaction, quality measures, and no-show rates. Future research should be done
      to determine effects of the long block on education and patient care in the long
      term, and elucidate which aspects of the long block most contribute to
      improvement.

PMID- 18612719
TI  - A self-instructional model to teach systems-based practice and practice-based
      learning and improvement.
AB  - BACKGROUND: When mandated as resident competencies in 1999, systems-based
      practice (SBP) and practice-based learning and improvement (PBLI) were new
      concepts to many. OBJECTIVE: To describe and evaluate a 4-week clinical elective
      (Achieving Competence Today-ACT) to teach residents SBP and PBLI. DESIGN: ACT
      consisted of a four-week active learning course and follow-up teaching
      experience, guided and supported by web-based materials. The curriculum included
      readings, scheduled activities, work products including an improvement project,
      and weekly meetings with a non-expert preceptor. The evaluation used a before
      after cross-comparison of ACT residents and their peers. PARTICIPANTS: Seventy
      eight residents and 42 faculty in 18 US Internal Medicine residency programs
      participated between 2003 and 2005. RESULTS AND MAIN MEASUREMENTS: All residents
      and faculty preceptors responded to a knowledge test, survey of attitudes, and
      self-assessment of competency to do 15 tasks related to SBP/PBLI. All measures
      were normalized to a 100-point scale. Each program's principal investigator (PI)
      identified aspects of ACT that were most and least effective in enhancing
      resident learning. ACT residents' gains in knowledge (4.4 on a 100-point scale)
      and self-assessed competency (11.3) were greater than controls' (-1.9, -8.0), but
      changes in attitudes were not significantly different. Faculty preceptors'
      knowledge scores did not change, but their attitudes became more positive (15.8).
      PIs found a ready-to-use curriculum effective (rated 8.5 on a 10-point scale).
      CONCLUSIONS: ACT increased residents' knowledge and self-assessment of their own
      competency and raised faculty's assessment of the importance of residents'
      learning SBP/PBLI. Faculty content expertise is not required for residents to
      learn SBP/PBLI.

PMID- 18612720
TI  - The effect of physician continuity on diabetic outcomes in a resident continuity
      clinic.
AB  - BACKGROUND: Conflicting data exists regarding the effect of continuity on
      diabetes care. Resident physicians frequently treat patients with diabetes in
      their continuity clinics; however, maintaining continuity in a resident clinic
      can be very challenging. OBJECTIVE: To determine if resident continuity is
      associated with improvement in diabetic outcomes (HgA1c, LDL, blood pressure) in
      a resident clinic. DESIGN AND SETTING: Retrospective analysis of data obtained
      from a medical record review of diabetic patients seen in a resident physician
      clinic. MEASUREMENTS: We measured continuity, using the Usual Provider of
      Continuity Index (UPC) for residents and faculty preceptors. We measured changes
      in HgA1c, LDL, and blood pressure over a 3-year period. Using repeated measures
      analysis of variance (ANOVA), we assessed the relationship between UPC and change
      in these diabetic outcomes. RESULTS: The resident UPC was 0.43, and the faculty
      preceptor UPC was 0.76. The overall change in HgA1c was -0.3. There was a
      statistically significant relationship between improvement in HgA1c and resident
      UPC (p = 0.02), but not faculty preceptor UPC. There was no association between
      resident or faculty preceptor continuity and change in LDL or blood pressure.
      CONCLUSION: This study showed a link between resident continuity and improvement
      in glycemic control in diabetic patients. Resident physicians have a greater
      opportunity to develop a personal relationship with their patients. This
      interpersonal continuity may be of benefit in patients with illnesses that
      requires a significant amount of self-management behaviors. Medical training
      programs should focus efforts on improving continuity in resident primary care
      clinics.

PMID- 18612721
TI  - Know when to rock the boat: how faculty rationalize students' behaviors.
AB  - BACKGROUND: When faculty evaluate medical students' professionalism, they make
      judgments based on the observation of behaviors. However, we lack an
      understanding of why they feel certain behaviors are appropriate (or not).
      OBJECTIVE: To explore faculty's reasoning around potential student behaviors in
      professionally challenging situations. DESIGN: Guided interviews with faculty who
      were asked to respond to 5 videotaped scenarios depicting students in
      professionally challenging situations. SUBJECTS: Purposive sample of 30 attending
      Internists and surgeons. APPROACH: Transcripts were analyzed using modified
      grounded theory to search for emerging themes and to attempt to validate a
      previous framework based on student responses. RESULTS: Faculty's reasoning
      around behaviors were similar to students' and were categorized by three general
      themes: Imperatives (e.g., take care of patients, behave honestly, know your
      place), Affect (factors relating to a student's "gut instincts" or personality),
      or Implications (for the student, patients, and others). Several new themes
      emerged, including "know when to fudge the truth", "do what you're told", and
      "know when to step up to the plate". These new codes, along with a near
      ubiquitous reference to Affect, suggests that faculty feel students are
      responsible for knowing when (and how) to bend the rules. Potential reasons for
      this are discussed. CONCLUSIONS: Although faculty are aware of the conflicts
      students face when encountering professional challenges, their reliance on
      students to "just know" what to do reflects the underlying complexity and
      ambiguity that surrounds decision making in these situations. To fully understand
      professional decision-making, we must acknowledge and address these issues from
      both students' and faculty's points of view.

PMID- 18612722
TI  - Can compassion be taught? Let's ask our students.
AB  - BACKGROUND: Medical educators act on the belief that students benefit from formal
      and informal educational experiences that foster virtues such as compassion,
      altruism, and respect for patients. OBJECTIVE: The purpose of this study is to
      examine fourth year medical students' perspectives on how, where, and by whom
      they believe the virtues associated with good physicianhood have been taught to
      them. DESIGN: Fourth year students were assigned a two- to three-page essay that
      asked them to reflect on how their medical education had "fostered and hindered"
      their conceptions of compassion, altruism, and respect for patients.
      PARTICIPANTS: All 112 students completed this assignment, and 52 (46%) gave us
      permission to use their essays for this study. APPROACH: An inductive,
      qualitative approach was used to develop themes derived from students' essays.
      RESULTS: Students' thoughts were organized around the idea of influences in three
      areas to which they consistently referred. Foundational influences included
      parents and "formative years," religious faith, and other experiences preceding
      medical school. Preclinical education influences comprised formal classroom
      experiences (both positive and negative effects). Clinical education influences
      included role modeling (both positive and negative) and the clinical environment
      (notable for emphasis on efficiency and conflicting cues). Students' essays drew
      most heavily on the effects of role modeling. DISCUSSION: Medical students arrive
      at our doors as thoughtful, compassionate people. Positive role models and
      activities to promote critical self-reflection may help nurture these attitudes.

PMID- 18612723
TI  - The intersection of online social networking with medical professionalism.
AB  - AIM: To measure the frequency and content of online social networking among
      medical students and residents. METHODS: Using the online network Facebook, we
      evaluated online profiles of all medical students (n = 501) and residents (n =
      312) at the University of Florida, Gainesville. Objective measures included the
      existence of a profile, whether it was made private, and any personally
      identifiable information. Subjective outcomes included photographic content,
      affiliated social groups, and personal information not generally disclosed in a
      doctor-patient encounter. RESULTS: Social networking with Facebook is common
      among medical trainees, with 44.5% having an account. Medical students used it
      frequently (64.3%) and residents less frequently (12.8%, p < .0001). The majority
      of accounts (83.3%) listed at least 1 form of personally identifiable
      information, only a third (37.5%) were made private, and some accounts displayed
      potentially unprofessional material. There was a significant decline in
      utilization of Facebook as trainees approached medical or residency graduation
      (first year as referent, years 3 and 4, p < .05). DISCUSSION: While social
      networking in medical trainees is common in the current culture of emerging
      professionals, a majority of users allow anyone to view their profile. With a
      significant proportion having subjectively inappropriate content, ACGME
      competencies in professionalism must include instruction on the intersection of
      personal and professional identities.

PMID- 18612724
TI  - Between two worlds: a multi-institutional qualitative analysis of students'
      reflections on joining the medical profession.
AB  - BACKGROUND: Recent changes in healthcare system and training mandates have
      altered the clinical learning environment. We incorporated reflective writing
      into Internal Medicine clerkships (IMcs) in multiple institutions so students
      could consider the impact of clerkship experiences on their personal and
      professional development. We analyzed student reflections to inform curricula and
      support learning. METHODS: We qualitatively analyzed the reflections of students
      at 3 US medical schools during IMcs (N = 292) to identify themes, tone, and
      reflective quality using an iterative approach. Chi-square tests assessed
      differences between these factors and across institutions. FINDINGS: Students
      openly described powerful experiences. Major themes focused on 4 categories:
      personal issues (PI), professional development (PD), relational issues (RI), and
      medical care (MC). Each major theme was represented at each institution, although
      with significant variability between institutions in many of the subcategories
      including student role (PI), development-as-a-physician (PD), professionalism
      (PD) (p < 0.001). Students used positive tones to describe student role,
      development-as-a-physician and physician-patient relationship (PD) (p < 0.01
      0.001), and negative tones for quality and safety (MC) (p < 0.05). Only 4% of
      writings coded as professionalism had a positive tone. Students employed a
      "reporting" voice in writing about clinical problem-solving, healthcare systems,
      and quality/safety (MC). DISCUSSION: Reflection is considered important to
      professional development. Our analysis suggests that students at 3 institutions
      reflect on similar experiences. Theme variability across institutions implies
      curricula should be tailored to local culture. Reflective quality analysis
      suggests students are better equipped to reflect on certain experiences over
      others, which may impact learning. Student reflections can function as a mirror
      for our organizations, offer institutional feedback for support and improvement,
      and inform curricula for learners and faculty.

PMID- 18612725
TI  - A professional development course for the clinical clerkships: developing a
      student-centered curriculum.
AB  - INTRODUCTION: Although professional development is addressed throughout the
      medical school curriculum, it is particularly salient to third-year students as
      they become integral members of health care teams. AIM: We present a professional
      development curriculum for third-year medical students. SETTING: Urban medical
      school. PROGRAM DESCRIPTION: In 2005, our curriculum consisted of 3 large group
      panels, each followed by a small group, occurring after the first, third, and
      last clerkship. Before each small group, students prepared critical incident
      reports, which led to focused group reflection. The individual topics were,
      respectively: (1) transition to clerkship learning; (2) challenges to
      professional behavior; and (3) medical errors. In 2006, based on student
      feedback, we piloted a revised student-centered panel on professionalism that was
      based entirely on themes from students' critical incident reports. PROGRAM
      EVALUATION: Students rated the curriculum well overall. In 2005-2006, the small
      groups ranged from 3.95 to 3.98 (SD 0.88) on a 5-point Likert scale (1 = poor, 5
      = excellent) and the panels ranged from 3.54 to 4.41 (SD 0.9). The pilot panel in
      2006 was rated 4.38 (SD 0.80). The most common professionalism themes generated
      from 185 critical incident reports were communication, compassionate patient
      care, accountability, and team collaboration. DISCUSSION: A professional
      development curriculum, consisting of panels, small groups, and critical incident
      reports, can promote reflection among third-year medical students.

PMID- 18612726
TI  - Impact of a 360-degree professionalism assessment on faculty comfort and skills
      in feedback delivery.
AB  - BACKGROUND: Professionalism is identified as a competency of resident education.
      Best approaches to teaching and evaluating professionalism are unknown, but
      feedback about professionalism is necessary to change practice and behavior.
      Faculty discomfort with professionalism may limit their delivery of feedback to
      residents. OBJECTIVES: A pilot program to implement a 360-degree evaluation of
      observable professionalism behaviors and determine how its use impacts faculty
      feedback to residents. DESIGN: Internal Medicine (IM) residents were evaluated
      during ambulatory rotations using a 360-degree assessment of professional
      behaviors developed by the National Board of Medical Examiners(R). Faculty used
      evaluation results to provide individual feedback to residents.
      PATIENTS/PARTICIPANTS: Fifteen faculty members. MEASUREMENTS AND MAIN RESULTS:
      Faculty completed pre- and post-intervention surveys. Using a 7-point Likert
      scale, faculty reported increased skill in giving general feedback (4.85 vs 4.36,
      p < .05) and feedback about professionalism (4.71 vs 3.57, p < .01) after the
      implementation of the 360-degree evaluation. They reported increased comfort
      giving feedback about professionalism (5.07 vs 4.35, p < .05) but not about
      giving feedback in general (5.43 vs 5.50). CONCLUSIONS: A 360-degree
      professionalism evaluation instrument used to guide feedback to residents
      improves faculty comfort and self-assessed skill in giving feedback about
      professionalism.

PMID- 18612727
TI  - Interactive spaced-education to teach the physical examination: a randomized
      controlled trial.
AB  - BACKGROUND: Several studies have documented that physical examination knowledge
      and skills are limited among medical trainees. OBJECTIVES: The objective of the
      study is to investigate the efficacy and acceptability of a novel online
      educational methodology termed 'interactive spaced-education' (ISE) as a method
      to teach the physical examination. DESIGN: The design of the study is randomized
      controlled trial. PARTICIPANTS: All 170 second-year students in the physical
      examination course at Harvard Medical School were eligible to enroll.
      MEASUREMENTS: Spaced-education items (questions and explanations) were developed
      on core physical examination topics and were content-validated by two experts.
      Based on pilot-test data, 36 items were selected for inclusion. Students were
      randomized to start the 18-week program in November 2006 or 12 weeks later.
      Students were sent 6 spaced-education e-mails each week for 6 weeks (cycle 1)
      which were then repeated in two subsequent 6-week cycles (cycles 2 and 3).
      Students submitted answers to the questions online and received immediate
      feedback. An online end-of-program survey was administered. RESULTS: One-hundred
      twenty students enrolled in the trial. Cycles 1, 2, and 3 were completed by 88%,
      76%, and 71% of students, respectively. Under an intent-to-treat analysis, cycle
      3 scores for cohort A students [mean 74.0 (SD 13.5)] were significantly higher
      than cycle 1 scores for cohort B students [controls; mean 59.0 (SD 10.5); P <
      .001], corresponding to a Cohen's effect size of 1.43. Eighty-five percent of
      participants (102 of 120) recommended the ISE program for students the following
      year. CONCLUSIONS: ISE can generate significant improvements in knowledge of the
      physical examination and is very well-accepted by students.

PMID- 18612728
TI  - Automatic capture of student notes to augment mentor feedback and student
      performance on patient write-ups.
AB  - OBJECTIVE: To determine whether the integration of an automated electronic
      clinical portfolio into clinical clerkships can improve the quality of feedback
      given to students on their patient write-ups and the quality of students' write
      ups. DESIGN: The authors conducted a single-blinded, randomized controlled study
      of an electronic clinical portfolio that automatically collects all students'
      clinical notes and notifies their teachers (attending and resident physicians)
      via e-mail. Third-year medical students were randomized to use the electronic
      portfolio or traditional paper means. Teachers in the portfolio group provided
      feedback directly on the student's write-up using a web-based application.
      Teachers in the control group provided feedback directly on the student's write
      up by writing in the margins of the paper. Outcomes were teacher and student
      assessment of the frequency and quality of feedback on write-ups, expert
      assessment of the quality of student write-ups at the end of the clerkship, and
      participant assessment of the value of the electronic portfolio system. RESULTS:
      Teachers reported giving more frequent and detailed feedback using the portfolio
      system (p = 0.01). Seventy percent of students who used the portfolio system,
      versus 39% of students in the control group (p = 0.001), reported receiving
      feedback on more than half of their write-ups. Write-ups of portfolio students
      were rated of similar quality to write-ups of control students. Teachers and
      students agreed that the system was a valuable teaching tool and easy to use.
      CONCLUSIONS: An electronic clinical portfolio that automatically collects
      students' clinical notes is associated with improved teacher feedback on write
      ups and similar quality of write-ups.

PMID- 18612729
TI  - Adapting web-based instruction to residents' knowledge improves learning
      efficiency: a randomized controlled trial.
AB  - BACKGROUND: Increased clinical demands and decreased available time accentuate
      the need for efficient learning in postgraduate medical training. Adapting Web
      based learning (WBL) to learners' prior knowledge may improve efficiency.
      OBJECTIVE: We hypothesized that time spent learning would be shorter and test
      scores not adversely affected for residents who used a WBL intervention that
      adapted to prior knowledge. DESIGN: Randomized, crossover trial. SETTING:
      Academic internal medicine residency program continuity clinic. PARTICIPANTS: 122
      internal medicine residents. INTERVENTIONS: Four WBL modules on ambulatory
      medicine were developed in standard and adaptive formats. The adaptive format
      allowed learners who correctly answered case-based questions to skip the
      corresponding content. MEASUREMENTS AND MAIN RESULTS: The measurements were
      knowledge posttest, time spent on modules, and format preference. One hundred
      twenty-two residents completed at least 1 module, and 111 completed all 4.
      Knowledge scores were similar between the adaptive format (mean +/- standard
      error of the mean, 76.2 +/- 0.9) and standard (77.2 +/- 0.9, 95% confidence
      interval [CI] for difference -3.0 to 1.0, P = .34). However, time spent was lower
      for the adaptive format (29.3 minutes [CI 26.0 to 33.0] per module) than for the
      standard (35.6 [31.6 to 40.3]), an 18% decrease in time (CI 9 to 26%, P = .0003).
      Seventy-two of 96 respondents (75%) preferred the adaptive format. CONCLUSIONS:
      Adapting WBL to learners' prior knowledge can reduce learning time without
      adversely affecting knowledge scores, suggesting greater learning efficiency. In
      an era where reduced duty hours and growing clinical demands on trainees and
      faculty limit the time available for learning, such efficiencies will be
      increasingly important. For clinical trial registration, see
      http://www.clinicaltrials.gov NCT00466453 (
      http://www.clinicaltrials.gov/ct/show/NCT00466453?order=1 ).

PMID- 18612730
TI  - Formal art observation training improves medical students' visual diagnostic
      skills.
AB  - BACKGROUND: Despite evidence of inadequate physical examination skills among
      medical students, teaching these skills has declined. One method of enhancing
      inspection skills is teaching "visual literacy," the ability to reason physiology
      and pathophysiology from careful and unbiased observation. OBJECTIVE: To improve
      students' visual acumen through structured observation of artworks, understanding
      of fine arts concepts and applying these skills to patient care. DESIGN:
      Prospective, partially randomized pre- vs. post-course evaluation using mixed
      methods data analysis. PARTICIPANTS: Twenty-four pre-clinical student
      participants were compared to 34 classmates at a similar stage of training.
      INTERVENTION: Training the Eye: Improving the Art of Physical Diagnosis consists
      of eight paired sessions of art observation exercises with didactics that
      integrate fine arts concepts with physical diagnosis topics and an elective life
      drawing session. MEASUREMENTS: The frequency of accurate observations on a 1-h
      visual skills examination was used to evaluate pre- vs. post-course descriptions
      of patient photographs and art imagery. Content analysis was used to identify
      thematic categories. All assessments were blinded to study group and pre- vs.
      post-course evaluation. RESULTS: Following the course, class participants
      increased their total mean number of observations compared to controls (5.41 +/-
      0.63 vs. 0.36 +/- 0.53, p < 0.0001) and had increased sophistication in their
      descriptions of artistic and clinical imagery. A 'dose-response' was found for
      those who attended eight or more sessions, compared to participants who attended
      seven or fewer sessions (6.31 + 0.81 and 2.76 + 1.2, respectively, p = 0.03).
      CONCLUSIONS: This interdisciplinary course improved participants' capacity to
      make accurate observations of art and physical findings.

PMID- 18612731
TI  - Teaching medication reconciliation through simulation: a patient safety
      initiative for second year medical students.
AB  - INTRODUCTION: Errors in medication reconciliation constitute a large area of
      potential injury to patients. Medication reconciliation is rarely incorporated
      into medical school curriculums so students learn primarily from observing
      clinical care. AIM: To design and implement an interactive learning exercise to
      teach second year medical students about medication reconciliation SETTING:
      Northwestern University Feinberg School of Medicine, Chicago, IL PROGRAM
      DESCRIPTION: The Medication Reconciliation Simulation teaches medical students
      how to elicit information from active real-world sources to reconcile a
      medication history. PROGRAM EVALUATION: At the conclusion of the session,
      students completed a Likert scale survey rating the level of improvement in their
      knowledge and comfort in obtaining medication histories. Students rated their
      knowledge level as having increased by 27% and their comfort level as having
      increased by 20%. A full 91% of the 158 students felt that it should be performed
      again for the following medical student class. DISCUSSION: The Medication
      Reconciliation Simulation is the first to specifically target medication
      reconciliation as a curriculum topic for medical students. Students praised the
      entertaining simulation and felt it provided a very meaningful experience on the
      patient safety topic. This simulation is generalizable to other institutions
      interested in teaching medication reconciliation and improving medication safety.

PMID- 18612732
TI  - Impact of the foundations of clinical medicine course on USMLE scores.
AB  - BACKGROUND: The synthesis of basic and clinical science knowledge during the
      clerkship years has failed to meet educational expectations. OBJECTIVES: We
      hypothesized that a small-group course emphasizing the basic science
      underpinnings of disease, Foundations of Clinical Medicine (FCM), could be
      integrated into third year clerkships and would not negatively impact the United
      States Medical Licensure Examination (USMLE) step 2 scores. DESIGN: In 2001-2002,
      all third year students met weekly in groups of 8-12 clustered within clerkships
      to discuss the clinical and basic science aspects of prescribed, discipline
      specific cases. PARTICIPANTS: Students completing USMLE step 2 between 1999 and
      2004 (n = 743). MEASUREMENTS: Course evaluations were compared with the overall
      institutional average. Bivariate analyses compared the mean USMLE steps 1 and 2
      scores across pre- and post-FCM student cohorts. We used multiple linear
      regression to assess the association between USMLE step 2 scores and FCM cohort
      controlling for potential confounders. RESULTS: Students' average course
      evaluation score rose from 66 to 77 (2001-2004) compared to an institutional
      average of 73. The unadjusted mean USMLE step 1 score was higher for the post-FCM
      cohort (212.9 vs 207.5, respectively, p < .001) and associated with step 2 scores
      (estimated coefficient = 0.70, p < .001). Post-FCM cohort (2002-2004; n = 361)
      mean step 2 scores topped pre-FCM (1999-2001; n = 382) scores (215.9 vs 207.7,
      respectively, p < .001). FCM cohort remained a significant predictor of higher
      step 2 scores after adjustment for USMLE step 1 and demographic characteristics
      (estimated coefficient = 4.3, p = .002). CONCLUSIONS: A curriculum integrating
      clinical and basic sciences during third year clerkships is feasible and
      associated with improvement in standardized testing.

PMID- 18612733
TI  - Working with patients with alcohol problems: a controlled trial of the impact of
      a rich media web module on medical student performance.
AB  - INTRODUCTION/AIMS: We designed an interactive web module to improve medical
      student competence in screening and interventions for hazardous drinking. We
      assessed its impact on performance with a standardized patient (SP) vs.
      traditional lecture. SETTING: First year medical school curriculum. PROGRAM
      DESCRIPTION: The web module included pre/posttests, Flash(c), and text didactics.
      It centered on videos of two alcohol cases, each contrasting a novice with an
      experienced physician interviewer. The learner free-text critiqued each clip then
      reviewed expert analysis. PROGRAM EVALUATION: First year medical students
      conveniently assigned to voluntarily complete a web module (N = 82) or lecture (N
      = 81) were rated by a SP in a later alcohol case. Participation trended higher
      (82% vs. 72%, p < .07) among web students, with an additional 4 lecture-assigned
      students crossing to the web module. The web group had higher mean scores on
      scales of individual components of brief intervention (assessment and decisional
      balance) and a brief intervention composite score (1-13 pt.; 9 vs. 7.8, p < .02)
      and self-reported as better prepared for the SP case. CONCLUSIONS: A web module
      for alcohol use interview skills reached a greater proportion of voluntary
      learners and was associated with equivalent overall performance scores and higher
      brief intervention skills scores on a standardized patient encounter.

PMID- 18612734
TI  - The state of evaluation in internal medicine residency.
AB  - BACKGROUND: There are no nationwide data on the methods residency programs are
      using to assess trainee competence. The Accreditation Council for Graduate
      Medical Education (ACGME) has recommended tools that programs can use to evaluate
      their trainees. It is unknown if programs are adhering to these recommendations.
      OBJECTIVE: To describe evaluation methods used by our nation's internal medicine
      residency programs and assess adherence to ACGME methodological recommendations
      for evaluation. DESIGN: Nationwide survey. PARTICIPANTS: All internal medicine
      programs registered with the Association of Program Directors of Internal
      Medicine (APDIM). MEASUREMENTS: Descriptive statistics of programs and tools used
      to evaluate competence; compliance with ACGME recommended evaluative methods.
      RESULTS: The response rate was 70%. Programs were using an average of 4.2-6.0
      tools to evaluate their trainees with heavy reliance on rating forms. Direct
      observation and practice and data-based tools were used much less frequently.
      Most programs were using at least 1 of the Accreditation Council for Graduate
      Medical Education (ACGME)'s "most desirable" methods of evaluation for all 6
      measures of trainee competence. These programs had higher support staff to
      resident ratios than programs using less desirable evaluative methods.
      CONCLUSIONS: Residency programs are using a large number and variety of tools for
      evaluating the competence of their trainees. Most are complying with ACGME
      recommended methods of evaluation especially if the support staff to resident
      ratio is high.

PMID- 18612735
TI  - Associations between United States Medical Licensing Examination (USMLE) and
      Internal Medicine In-Training Examination (IM-ITE) scores.
AB  - BACKGROUND: Little is known about the associations of previous standardized
      examination scores with scores on subsequent standardized examinations used to
      assess medical knowledge in internal medicine residencies. OBJECTIVE: To examine
      associations of previous standardized test scores on subsequent standardized test
      scores. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred ninety-five
      internal medicine residents. METHODS: Bivariate associations of United States
      Medical Licensing Examination (USMLE) Steps and Internal Medicine In-Training
      Examination (IM-ITE) scores were determined. Random effects analysis adjusting
      for repeated administrations of the IM-ITE and other variables known or
      hypothesized to affect IM-ITE score allowed for discrimination of associations of
      individual USMLE Step scores on IM-ITE scores. RESULTS: In bivariate
      associations, USMLE scores explained 17% to 27% of the variance in IME-ITE
      scores, and previous IM-ITE scores explained 66% of the variance in subsequent IM
      ITE scores. Regression coefficients (95% CI) for adjusted associations of each
      USMLE Step with IM-ITE scores were USMLE-1 0.19 (0.12, 0.27), USMLE-2 0.23 (0.17,
      0.30), and USMLE-3 0.19 (0.09, 0.29). CONCLUSIONS: No single USMLE Step is more
      strongly associated with IM-ITE scores than the others. Because previous IM-ITE
      scores are strongly associated with subsequent IM-ITE scores, appropriate
      modeling, such as random effects methods, should be used to account for previous
      IM-ITE administrations in studies for which IM-ITE score is an outcome.

PMID- 18612736
TI  - The association of student examination performance with faculty and resident
      ratings using a modified RIME process.
AB  - BACKGROUND: RIME is a descriptive framework in which students and their teachers
      can gauge progress throughout a clerkship from R (reporter) to I (interpreter) to
      M (manager) to E (educator). RIME, as described in the literature, is
      complemented by residents and attending physicians meeting with a clerkship
      director to discuss individual student progress, with group discussion resulting
      in assignment of a RIME stage. OBJECTIVE: 1) to determine whether a student's
      RIME rating is associated with end-of-clerkship examination performance; and 2)
      to determine whose independent RIME rating is most predictive of a student's
      examination performance: attendings, residents, or interns. DESIGN: Prospective
      cohort study. PARTICIPANTS: Third year medical students from academic years 2004
      2005 and early 2005-2006 at 1 medical school. MEASUREMENTS AND MAIN RESULTS: Each
      attending, resident, and intern independently assessed the student's final RIME
      stage attained. For the purpose of analysis, R stage=1, I=2, M=3, and E=4.
      Regression analyses were performed with examination scores as dependent variables
      (National Board of Medical Examiners [NBME] medicine subject examination and a
      clinical performance examination [CPE]), with independent variables of mean
      attending RIME score, mean resident score, and mean intern score. For the 122
      students, significant predictors of NBME subject exam score were resident RIME
      rating (p = .008) and intern RIME rating (p = .02). Significant predictor of CPE
      performance was resident RIME rating (p = .01). CONCLUSION: House staff RIME
      ratings of students are associated with student performance on written and
      clinical skills examinations.

PMID- 18612737
TI  - Resident identification of learning objectives after performing self-assessment
      based upon the ACGME core competencies.
AB  - BACKGROUND: Self-assessment is increasingly being incorporated into competency
      evaluation in residency training. Little research has investigated the
      characteristics of residents' learning objectives and action plans after self
      assessment. OBJECTIVE: To explore the frequency and specificity of residents'
      learning objectives and action plans after completing either a highly or
      minimally structured self-assessment. DESIGN: Internal Medicine residents (N =
      90) were randomized to complete a highly or minimally structured self-assessment
      instrument based on the Accreditation Council for Graduate Medical Education Core
      Competencies. All residents then identified learning objectives and action plans.
      MEASUREMENTS: Learning objectives and action plans were analyzed for content.
      Differences in specificity and content related to form, gender, and training
      level were assessed. RESULTS: Seventy-six residents (84% response rate)
      identified 178 learning objectives. Objectives were general (79%), most often
      focused on medical knowledge (40%), and were not related to the type of form
      completed (p > 0.01). "Reading more" was the most common action plan.
      CONCLUSIONS: Residents commonly identify general learning objectives focusing on
      medical knowledge regardless of the structure of the self-assessment form. Tools
      and processes that further facilitate self-assessment should be identified.

PMID- 18612738
TI  - Innovative health care disparities curriculum for incoming medical students.
AB  - PURPOSE: 1) To pilot a health disparities curriculum for incoming first year
      medical students and evaluate changes in knowledge. 2) To help students become
      aware of personal biases regarding racial and ethnic minorities. 3) To inspire
      students to commit to serving indigent populations. METHODS: First year students
      participated in a 5-day elective course held before orientation week. The course
      used the curricular goals that had been developed by the Society of General
      Internal Medicine Health Disparities Task Force. Thirty-two faculty members from
      multiple institutions and different disciplinary backgrounds taught the course.
      Teaching modalities included didactic lectures, small group discussions, off-site
      expeditions to local free clinics, community hospitals and clinics, and student
      led poster session workshops. The course was evaluated by pre-post surveys.
      RESULTS: Sixty-four students (60% of matriculating class) participated. Survey
      response rates were 97-100%. Students' factual knowledge (76 to 89%, p < .0009)
      about health disparities and abilities to address disparities issues improved
      after the course. This curriculum received the highest rating of any course at
      the medical school (overall mean 4.9, 1 = poor, 5 = excellent). CONCLUSIONS: This
      innovative course provided students an opportunity for learning and exploration
      of a comprehensive curriculum on health disparities at a critical formative time.

PMID- 18612739
TI  - A longitudinal medical Spanish program at one US medical school.
AB  - INTRODUCTION: Policymakers have recommended recruiting or training (or both) more
      US physicians who can provide care in Spanish. Few longitudinal medical Spanish
      programs have been described and evaluated. OBJECTIVE: This study aims to
      describe development and evaluation of the preclinical phase of a 4-y program
      designed to graduate physicians who can provide language-concordant care in
      Spanish. SETTING: Study was done in one public medical school in southeastern
      USA. PROGRAM DESCRIPTION: The program targeted intermediate/advanced Spanish
      speakers. Standardized fluency assessments were used to determine eligibility and
      evaluate participants' progress. Curriculum included didactic coursework,
      simulated patients, socio-cultural seminars, clinical skills rotations at sites
      serving Latinos, service-learning, and international immersion. PROGRAM
      EVALUATION: For the first two cohorts (n = 45) qualitative evaluation identified
      program improvement opportunities and found participants believed the program
      helped them maintain their Spanish skills. Mean interim (2-y) speaking
      proficiency scores were unchanged from baseline: 9.0 versus 8.7 at baseline on 12
      point scale (p = 0.15). Mean interim listening comprehension scores (second
      cohort only, n = 25) increased from a baseline of 77 to 86% (p = 0.003).
      Proportions "passing" the listening comprehension test increased from 72 to 92%
      (p = 0.06). DISCUSSION: We describe development of a longitudinal Spanish program
      within a medical school. Participation was associated with improved Spanish
      listening comprehension and no change in speaking proficiency.

PMID- 18612740
TI  - Teaching residents to work with torture survivors: experiences from the Bronx
      Human Rights Clinic.
AB  - INTRODUCTION: Despite the 1984 United Nations's Convention Against Torture
      calling to train doctors to work with torture survivors, many physicians are
      unaware of their obligation and few are taught the requisite clinical skills.
      AIM: To describe the development, implementation, and evaluation of a curriculum
      to teach residents to work with torture survivors. PARTICIPANTS: Medicine
      residents in New York City PROGRAM DESCRIPTION: A 2-component curriculum
      consisting of a series of workshops and clinical experiences, which provide
      content, skills, and practices regarding the medical, psychological, ethical, and
      legal aspects of evaluating and caring for torture survivors. CURRICULUM
      EVALUATION: All 22 trainees received surveys before and after training. Surveys
      assessed residents' relevant prior experience, beliefs, skills, and attitudes
      regarding working with torture survivors. At baseline, 23% of residents described
      previous human rights trainings and 17% had work experiences with torture
      survivors. Before the curriculum, 81% of residents reported doctors should know
      how to evaluate survivors, although only 5% routinely screened patients for
      torture. After the curriculum, residents reported significant improvements in 3
      educational domains-general knowledge, sequelae, and self-efficacy to evaluate
      torture survivors. DISCUSSION: This curriculum addresses the disparity between
      doctors' obligations, and training to work with torture survivors. It is likely
      to achieve its educational goals, and can potentially be adapted to other
      residencies.

PMID- 18612741
TI  - Impact of participation in a community-based intimate partner violence prevention
      program on medical students: a multi-center study.
AB  - BACKGROUND: Physicians are generally poorly trained to recognize, treat or refer
      adolescents at risk for intimate partner violence (IPV). Participation in
      community programs may improve medical students' knowledge, skills, and attitudes
      about IPV prevention. OBJECTIVE: To determine whether the experience of serving
      as educators in a community-based adolescent IPV prevention program improves
      medical students' knowledge, skills, and attitudes toward victims of IPV, beyond
      that of didactic training. PARTICIPANTS: One hundred and seventeen students
      attending 4 medical schools. DESIGN: Students were randomly assigned to didactic
      training in adolescent IPV prevention with or without participation as educators
      in a community-based adolescent IPV prevention program. Students assigned to
      didactic training alone served as community educators after the study was
      completed. MEASUREMENT: Knowledge, self-assessment of skills and attitudes about
      intimate partner violence and future plans to pursue outreach work. RESULTS: The
      baseline mean knowledge score of 10.25 improved to 21.64 after didactic training
      (p </= .001). Medical students in the "didactic plus outreach" group demonstrated
      higher levels of confidence in their ability to address issues of intimate
      partner violence, (mean = 41.91) than did students in the "didactic only" group
      (mean = 38.94) after controlling for initial levels of confidence (p </= .002).
      CONCLUSIONS: Experience as educators in a community-based program to prevent
      adolescent IPV improved medical students' confidence and attitudes in recognizing
      and taking action in situations of adolescent IPV, whereas participation in
      didactic training alone significantly improved students' knowledge.

PMID- 18612742
TI  - A model intensive course in geriatric teaching for non-geriatrician educators.
AB  - INTRODUCTION: Because of the aging demographics nearly all medical specialties
      require faculty who are competent to teach geriatric care principles to learners,
      yet many non-geriatrician physician faculty members report they are not prepared
      for this role. AIMS: To determine the impact of a new educational intervention
      designed to improve the self-efficacy and ability of non-geriatrician clinician
      educators to teach geriatric medicine principles to medical students and
      residents. DESCRIPTION: Forty-two non-geriatrician clinician-educator faculty
      from 17 academic centers self-selected to participate in a 3-day on-site
      interactive intensive course designed to increase knowledge of specific geriatric
      medicine principles and to enhance teaching efficacy followed by up to a year of
      mentorship by geriatrics faculty after participants return to their home
      institutions. On average, 24% of their faculty time was spent teaching and 57% of
      their clinical practices involved patients aged over 65 years. Half of all
      participants were in General Internal Medicine, and the remaining were from
      diverse areas of medicine. EVALUATION: Tests of geriatrics medical knowledge and
      attitudes were high at baseline and did not significantly change after the
      intervention. Self-rated knowledge about specific geriatric syndromes, self
      efficacy to teach geriatrics, and reported value for learning about geriatrics
      all improved significantly after the intervention. A quarter of the participants
      reported they had achieved at least one of their self-selected 6-month teaching
      goals. DISCUSSION: An intensive 3-day on-site course was effective in improving
      self-reported knowledge, value, and confidence for teaching geriatrics principles
      but not in changing standardized tests of geriatrics knowledge and attitudes in a
      diverse group of clinician-educator faculty. This intervention was somewhat
      associated with new teaching behaviors 6 months after the intervention. Longer
      term investigations are underway to determine the sustainability of the effect
      and to determine which factors predict the faculty who most benefit from this
      innovative model.

PMID- 18612743
TI  - Aiming to improve care of older adults: an innovative faculty development
      workshop.
AB  - INTRODUCTION/AIMS: Internists care for older adults and teach geriatrics to
      trainees, but they often feel ill-prepared for these tasks. The aims of our 1-day
      Continuing Medical Education workshop were to improve the knowledge and self
      perceived competence of general internists in their care of older adults and to
      increase their geriatrics teaching for learners. SETTING: Two internal medicine
      training programs encompassing University, Veterans Affairs, and a community
      based hospital in Portland, OR, USA. PROGRAM DESCRIPTION: Course faculty
      identified gaps in assessment of cognition, function, and decisional capacity;
      managing care transitions; and treatment of behavioral symptoms. To address these
      gaps, our workshop provided geriatric content discussions followed by small group
      role plays to apply newly learned content. Forty teaching faculty participated.
      PROGRAM EVALUATION: Participants completed 13-item multiple-choice pre- and post
      workshop geriatric knowledge tests, pre- and post-workshop surveys of self
      perceived competence to care for older adults, and completed an open-ended
      'commitment to change' prompt after the intervention. Knowledge scores improved
      following the intervention (61% to 72%, p < .0001), as did self-perceived
      competence (11 of 14 items significant). Seventy-one percent of participants
      reported success in meeting their commitment to change goals. DISCUSSION: A 1-day
      intervention improved teaching faculty knowledge and self-perceived competence to
      care for older patients and led to self-perceived changes in teaching behaviors.

PMID- 18612744
TI  - Evaluation of a longitudinal medical school evidence-based medicine curriculum: a
      pilot study.
AB  - BACKGROUND: Evidence-based medicine (EBM) is increasingly taught in medical
      schools, but few curricula have been evaluated using validated instruments.
      OBJECTIVE: To evaluate a longitudinal medical school EBM curriculum using a
      validated instrument. DESIGN, PARTICIPANTS, MEASUREMENTS: We evaluated EBM
      attitudes and knowledge of 32 medical students as they progressed through an EBM
      curriculum. The first part was an EBM "short course" with didactic and small
      group sessions occurring at the end of the second year. The second part
      integrated EBM assignments with third-year clinical rotations. The validated 15
      item Berlin Questionnaire was administered before the course, after the short
      course, and at the end of the third year. RESULTS: EBM knowledge scores increased
      from baseline by 2.8 points at the end of the second year portion of the course
      (p = .0001), and by 3.7 points at the end of the third year (p < .0001). Self
      rated EBM knowledge increased from baseline by 0.8 and 1.1 points, respectively
      (p = .0006 and p < .0001, respectively). EBM was felt to be of high importance
      for medical education and clinical practice at all time points, peaking after the
      short course. CONCLUSIONS: A longitudinal medical school EBM curriculum was
      associated with increased EBM knowledge. This knowledge increase was sustained
      throughout the curriculum.

PMID- 18612745
TI  - A pilot study using nominal group technique to assess residents' perceptions of
      successful attending rounds.
AB  - BACKGROUND: Ward attending rounds are fundamental for internal medicine residency
      training. An improved understanding of interns' and residents' perceptions of
      attending rounds should inform training programs and attending physicians.
      OBJECTIVES: The aim of this study was to assess residents' perceptions of
      successful attending rounds. DESIGN: We convened two groups of interns and two
      groups of residents, to elicit their perceptions on attending rounds. SUBJECTS:
      Participants were recruited by e-mail and conference announcements from the 49
      interns and 80 residents in the internal medicine and medicine-pediatrics
      residency programs. MEASUREMENTS: The nominal group technique (NGT) uses a
      structured group process to elicit and prioritize answers to a carefully
      articulated question. MAIN RESULTS: Seven interns (14%) identified 27 success
      factors and ranked attending approachability and enthusiasm and high quality
      teaching as most important. A second group of six (12%) interns identified 40
      detractors and ranked having "mean attendings," receiving disrespectful comments,
      and too long or too short rounds as the most significant detractors. Nine (11%)
      residents identified 32 success factors and ranked attention to length of rounds,
      house staff autonomy, and establishing goals/expectations as the most important
      success factors. A second group of six (8%) residents identified 34 detractors
      and ranked very long rounds, interruptions and time constraints, and poor rapport
      between team members as the most significant detractors). CONCLUSIONS: Although
      there was some overlap in interns' and residents' perceptions of attending
      rounds, interns identified interpersonal factors as the most important factors;
      whereas residents viewed structural factors as most important. These findings
      should assist attending physicians improve the way they conduct rounds targeting
      both interns and residents needs.

PMID- 18612746
TI  - Do internists, pediatricians, and psychiatrists feel competent in obesity care?:
      using a needs assessment to drive curriculum design.
AB  - BACKGROUND: Physicians must effectively evaluate and treat obesity. To design a
      needs-driven curriculum intended to improve patient outcomes, physicians were
      surveyed about their self-perceived knowledge and skills. OBJECTIVE: The
      objective of this study was to determine the expressed needs of residents and
      faculty regarding obesity care training across three specialties. DESIGN: The
      study used a survey given to faculty and residents in General Internal Medicine,
      Pediatrics, and Psychiatry. METHODS: Survey questions were generated from
      comprehensive nutrition curriculum and clinical recommendations, administered
      online, and then organized around a validated behavioral health framework-the 5As
      (assess, advise, agree, assist, arrange). Analyses were conducted to evaluate
      differences in perceived knowledge and skills between specialties and across
      training levels. RESULTS: From an overall response rate of 65% (65 residents and
      250 faculty members), nearly 20% reported inadequate competency in every item
      with 48% of respondents reporting an inability to adequately counsel patients
      about common treatment options. Internists reported the lowest competency in
      arranging referrals and follow-up. Psychiatrists reported the lowest competency
      in assessment skills. CONCLUSIONS: This survey demonstrated a critical need for
      training in specific areas of obesity care. The proposed curriculum targets these
      areas taking into consideration observed differences across specialties.

PMID- 18612747
TI  - Tobacco cessation and prevention practices reported by second and fourth year
      students at US medical schools.
AB  - BACKGROUND: Tobacco dependence counseling is recommended to be included as core
      curriculum for US medical students. To date, there has been little information on
      students' self-reported skills and practice opportunities to provide 5A's (Ask,
      Advise, Assess, Assist, and Arrange) counseling for tobacco cessation. METHODS:
      We conducted anonymous surveys of second year and fourth year students at
      multiple US medical schools between February 2004 and March 2005 (overall
      response rate 70%). We report on the tobacco control practices of the 860 second
      year and 827 fourth year students completing the survey. MEASUREMENTS AND MAIN
      RESULTS: Fourth year students reported multiple opportunities to learn tobacco
      counseling in case-based discussions, simulated patient encounters, and clinical
      skills courses. They reported more instruction in family medicine (79%) and
      Internal Medicine (70%) than Pediatrics (54%), Obstetrics/Gynecology (41%), and
      Surgery clerkships (16%). Compared with asking patients about smoking, advising
      smokers to quit, and assessing patient willingness to quit, fourth year students
      were less likely to have multiple practice opportunities to assist the patient
      with a quit plan and arrange follow-up contact. More than half of second year
      students reported multiple opportunities for asking patients about smoking but
      far fewer opportunities for practicing the other 4 As. CONCLUSIONS: By the
      beginning of their fourth year, most students in this group of medical schools
      reported multiple opportunities for training and practicing basic 5A counseling,
      although clear deficits for assisting patients with a quit plan and arranging
      follow-up care exist. Addressing these deficits and integrating tobacco teaching
      through tailored specific instruction across all clerkships, particularly in
      Surgery, Pediatrics, and Obstetrics/Gynecology is a challenge for medical school
      education.

PMID- 18612748
TI  - Effects of resident work hour limitations on faculty professional lives.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education resident
      work hour limitations were implemented in July, 2003. Effects on faculty are not
      well understood. OBJECTIVE: The objective of this study was to determine the
      effects of the resident work hour limitations on the professional lives of
      faculty physicians. DESIGN AND PARTICIPANTS: Survey of faculty physicians at
      three teaching hospitals associated with university-based internal medicine and
      surgery residency programs in Seattle, Washington. Physicians who attended on
      Internal Medicine and Surgery in-patient services during the 10 mo after
      implementation of work hour limitations were eligible for participation (N =
      366); 282 physicians (77%) returned surveys. MEASUREMENTS: Participants were
      asked about the effects of resident work hour limitations on aspects of their
      professional lives, including clinical work, research, teaching, and professional
      satisfaction. RESULTS: Most attending physicians reported that, because of work
      hour limitations, they spent more time on clinical work (52%), felt more
      responsibility for supervising patient care (65%), and spent less time on
      research or other academic pursuits (51%) and teaching residents (72%). Reported
      changes in work content were independently associated with the self-reported
      probability of leaving academic medicine in the next 3 y. CONCLUSIONS: Resident
      work hour limitations have had large effects on the professional lives of
      faculty. These findings may have important implications for recruiting and
      retaining faculty at academic medical centers.

PMID- 18612749
TI  - Impact of duty hour regulations on medical students' education: views of key
      clinical faculty.
AB  - BACKGROUND: Teaching faculty have valuable perspectives on the impact of
      residency duty hour regulations on medical students. OBJECTIVE: The objective of
      this study was to elicit faculty views on the impact of residency duty hour
      regulations on medical students' educational experience on inpatient medicine
      rotations. DESIGN AND PARTICIPANTS: We conducted a National Survey of Key
      Clinical Faculty (KCF) at 40 internal medicine residency programs affiliated with
      U.S. medical schools using a random sample stratified by National Institutes of
      Health funding and program size. MEASUREMENTS: This study measures KCF opinions
      on the effect of duty hour regulations on students' education. RESULTS: Of 154
      KCF targeted, 111 responded (72%). Fifty-two percent of KCF reported worsening in
      the overall quality of students' education compared to just 2.7% reporting
      improvement (p < 0.001). In multivariate analysis adjusted for gender, academic
      rank, specialty, and years of teaching experience, faculty who spent >/=15 hours
      per week teaching were more likely to report worsening in medical students' level
      of responsibility on inpatient teams [odds ratio (OR) 3.1; 95% confidence
      interval (CI) 1.3-7.6], ability to follow patients throughout hospitalization (OR
      3.2; 95% CI 1.3-7.9), ability to develop working relationships with residents (OR
      2.3; 95% CI 1.0-5.2), and the overall quality of students' education (OR 3.3; 95%
      CI 1.4-8.1) compared to faculty who spent less time teaching. CONCLUSION: Key
      clincal faculty report concerns about the impact of duty hour regulations on
      aspects of medical students' education in internal medicine. Medical schools and
      residency programs should identify ways to ensure optimal educational experiences
      for students within duty hour requirements.

PMID- 18612750
TI  - Measuring resident well-being: impostorism and burnout syndrome in residency.
AB  - BACKGROUND: Assessing resident well-being is becoming increasingly important from
      a programmatic standpoint. Two measures that have been used to assess this are
      the Clance Impostor Scale (CIS) and the Maslach Burnout Inventory-Human Services
      Survey (MBI-HSS). However, little is known about the relationship between the two
      phenomena. OBJECTIVES: To explore the prevalence and association between
      impostorism and burnout syndrome in a sample of internal medicine residents.
      DESIGN: Anonymous, cross-sectional postal survey. PARTICIPANTS: Forty-eight
      internal medicine residents (postgraduate year [PGY] 1-3) at the Schulich School
      of Medicine & Dentistry (62.3% response rate). MEASUREMENTS AND MAIN RESULTS:
      Short demographic questionnaire, CIS and MBI-HSS. Impostorism and burnout
      syndrome were identified in 43.8% and 12.5% of residents, respectively. With the
      exception of a negative correlation between CIS scores and the MBI's personal
      accomplishment subscale (r = -.30; 95% CI -.54 to -.02), no other significant
      relations were identified. Foreign-trained residents were more likely to score as
      impostors (odds ratio [OR] 10.7; 95% CI 1.2 to 98.2) while senior residents were
      more likely to experience burnout syndrome (OR 16.5 95% CI 1.6 to 168.5).
      CONCLUSIONS: Both impostorism and burnout syndrome appear to be threats to
      resident well-being in our program. The lack of relationship between the two
      would suggest that programs and researchers wishing to address the issue of
      resident distress should consider using both measures. The finding that foreign
      trained residents appear to be more susceptible to impostorism warrants further
      study.

PMID- 18612751
TI  - Changes in U.S. medical students' specialty interests over the course of medical
      school.
AB  - BACKGROUND: Studies have examined factors affecting medical students' specialty
      choice, but little research exists on stability of these specialty interests.
      OBJECTIVE: To describe patterns of change in specialty interests during medical
      school and examine associations between specialty change patterns and gender,
      desire for a high-prestige career, and interest in prevention. DESIGN: Medical
      students (Class of 2003) at 15 representative US schools were invited to complete
      surveys during freshman orientation, entry to wards, and senior year.
      PARTICIPANTS: This analysis used data from 942 students who completed all 3
      surveys. MEASUREMENTS: In addition to a number of other items, students were
      asked to choose the 1 specialty they were most interested in pursuing. RESULTS:
      The most common specialty choices among freshman students were pediatrics (20%)
      and surgery (18%); least common choices were psychiatry and preventive medicine
      (1% each). General internal medicine was the initial specialty choice for 8%.
      Most students changed their specialty choices, regardless of initial interest.
      Only 30% of those initially interested in primary care (PC) remained interested
      at all 3 time points, compared to 68% of those initially interested in non-PC.
      Female versus male students were more commonly interested in PC at all 3 time
      points. Senior students interested in non-PC specialties were more likely to
      desire a high-prestige career (48%) than those interested in PC (31%).
      CONCLUSIONS: Medical students may benefit from more intensive introduction to
      some specialties earlier in pre-medical and medical education. In addition,
      increasing the prestige of PC fields may shape the physician workforce.

PMID- 18612752
TI  - Internal medicine clerkship directors' perceptions about student interest in
      internal medicine careers.
AB  - BACKGROUND: Experienced medical student educators may have insight into the
      reasons for declining interest in internal medicine (IM) careers, particularly
      general IM. OBJECTIVE: To identify factors that, according to IM clerkship
      directors, influence students' decisions for specialty training in IM. DESIGN:
      Cross-sectional national survey. PARTICIPANTS: One hundred ten institutional
      members of Clerkship Directors in IM. MEASUREMENTS: Frequency counts and
      percentages were reported for descriptive features of clerkships, residency match
      results, and clerkship directors' perceptions of factors influencing IM career
      choice at participating schools. Perceptions were rated on a five-point scale (1
      = very much pushes students away from IM careers; 5 = very much attracts students
      toward IM careers). RESULTS: Survey response rate was 83/110 (76%); 80 answered
      IM career-choice questions. Clerkship directors identified three educational
      items attracting students to IM careers: quality of IM faculty (mean score 4.3,
      SD = 0.56) and IM rotation (4.1, SD = 0.67), and experiences with IM residents
      (3.9, SD = 0.94). Items felt most strongly to push students away from IM careers
      were current practice environment for internists (mean score 2.1, SD = 0.94),
      income (2.1, SD = 1.08), medical school debt (2.3, SD = 0.89), and work hours in
      IM (2.4, SD = 1.05). Factor analysis indicated three factors explaining students'
      career choices: value/prestige of IM, clerkship experience, and exposure to
      internists. CONCLUSIONS: IM clerkship directors believe that IM clerkship
      experiences attract students toward IM, whereas the income and lifestyle for
      practicing internists dissuade them. These results suggest that interventions to
      enhance the practice environment for IM could increase student interest in the
      field.

PMID- 18612753
TI  - The shift of residents from university to non-university hospitals in Japan: a
      survey study.
AB  - BACKGROUND: Between 2003 and 2004, when the new postgraduate medical education
      program was introduced in Japan, the number of university residents decreased
      from 5,923 to 3,264 (-31%), whereas the number of non-university residents
      increased from 2,243 to 4,110 (+45%). OBJECTIVE: To identify potential reasons
      for the shift of residents from university to non-university hospitals. DESIGN:
      Cross-sectional mailed survey. PARTICIPANTS: The subjects were 1,794 2nd-year
      residents at 91 university hospitals and 2,010 2nd-year residents at 659 non
      university hospitals. MEASUREMENTS: Data on hospital demographics, resident
      demographics, and resident satisfaction with training were collected in 2006 and
      were compared between university and non-university hospitals. RESULTS: Compared
      to non-university hospitals, university hospitals were more likely to have >700
      beds (55% vs. 10%, p<0.001) and to have more teaching resources and free access
      to international medical journals (84% vs. 62%, p<0.001). Nevertheless, one-half
      (47%) of the university residents reported that they were not satisfied with the
      residency system and clinical skills training and attributed their
      dissatisfaction to "daily chores," "low salary," and "poor clinical
      opportunities." Logistic regression analyses indicated that the proportions of
      residents who were satisfied with income (OR: 0.32, 95% CI: 0.26-0.40) and the
      residency system (OR: 0.52, 95% CI: 0.40-0.68) and clinical skills training (OR:
      0.77, 95% CI: 0.60-0.99) were significantly lower for university residents than
      for non-university residents. CONCLUSIONS: Hospital size and teaching resources
      do not overcome the other characteristics of university hospitals that lead to
      residents' dissatisfaction.

PMID- 18612754
TI  - Fulfilling the promise of hospital medicine: tailoring internal medicine training
      to address hospitalists' needs.
AB  - Categorical internal medicine (IM) residency training has historically
      effectively prepared graduates to manage the medical needs of acutely ill adults.
      The development of the field of hospital medicine, however, has resulted in
      hospitalists filling clinical niches that have been traditionally ignored or
      underemphasized in categorical IM training. Furthermore, hospitalists are
      increasingly leading inpatient safety, quality and efficiency initiatives that
      require understanding of hospital systems, multidisciplinary care and inpatient
      quality assessment and performance improvement. Taken in this context, many
      graduating IM residents are under-prepared to practice as effective hospitalists.
      In this paper, we outline the rationale for targeted training in hospital
      medicine and discuss the content and methods for delivering this training.

PMID- 18612755
TI  - The evidence is at hand for improving care in settings where residents train.

PMID- 18612756
TI  - Where we're headed: a new wave of scholarship on educating medical
      professionalism.

PMID- 18612757
TI  - Resident duty hours and the delicate balance between education and patient care.

PMID- 18612758
TI  - Residency training: beginning with the end in mind.

PMID- 18612759
TI  - Clinical and radiological features of brain neurotoxicity caused by antitumor and
      immunosuppressant treatments.
AB  - Antitumor and immunosuppressant treatment-related neurotoxicity can determine
      nonspecific clinical syndromes. Exclusion of other possible causes, among which
      tumor progression, appearance of paraneoplastic disease, renal or hepatic
      failure, diabetes or hypertension, is relevant. We report clinical and
      neuroradiological features in five patients with neurotoxic syndromes due to
      chemotherapy/radiotherapy or immunosuppression in the context of neoplastic
      disease/organ transplantation. Acute neurological syndrome developed in three
      patients after methotrexate (MTX), cyclosporine A, and L-asparaginase therapy,
      respectively. MRI showed posterior reversible encephalopathy in two cases and
      venous thrombosis with intraparenchymal hematoma in the third patient. Late onset
      clinical syndrome occurred in the last two patients, treated with MTX or
      radiation therapy for breast cancer metastasis and pituitary adenoma.
      Neuroimaging showed brain diffuse abnormalities. Patients affected by tumors
      suffer from increased risk for treatment-related toxicities. Appearance or
      worsening of neurological signs and symptoms challenge the clinician to
      discriminate between CNS involvement by the tumor, toxicity of drugs, parane
      oplastic disease and infections. MRI has a key role in differential diagnosis.
      Close interaction between the neurologist, the oncologist and the
      neuroradiologist leads to the optimal management of patients.

PMID- 18612760
TI  - Pneumonia in stroke patients with oropharyngeal dysphagia: a six-month follow-up
      study.
AB  - The aim of the study was to estimate the frequency of pneumonia and to determine
      the risk factors for this complication in poststroke patients with oropharyngeal
      dysphagia (OD). We prospectively followed up 67 patients (mean age 72.9+/-12.2
      years) in the first 6 months after stroke, during which time we recorded gender,
      stroke side, type of lesion, diabetes, history of chronic obstructive pulmonary
      disease (COPD), smoking, level of consciousness, functional outcome, dietary
      history, occurrence of chest infection, and death. Degree of OD and
      presence/absence of reflex cough was assessed by Fiberoptic Endoscopic Evaluation
      of Swallowing. Sixty patients showed complete recovery of prestroke swallowing; 9
      (13.4% IC 95%=5-20%) developed pneumonia, two of whom died. The first episode of
      pneumonia occurred in all nine patients within the first month after stroke
      onset. The pneumonia was associated with absence of reflex cough after swallow,
      COPD, and severe impairment of consciousness and poor functional outcome.

PMID- 18612761
TI  - The protective effect of fish n-3 fatty acids on cerebral ischemia in rat
      prefrontal cortex.
AB  - This study presents neuroprotective effects of fish n-3 EFA on the prefrontal
      cortex after cerebral ischemia and reperfusion. Eighteen rats divided into three
      groups. Group A rats were used as control. Cerebral ischemia and reperfusion was
      produced in rats either on a standard diet (Group B) or a standard diet plus fish
      n-3 EFA for 14 days (Group C). The malondialdehyde (MDA) levels and activities of
      superoxide dismutase (SOD) and catalase (CAT) were measured and the number of
      apoptotic neurons was counted. The levels of MDA and activities of SOD increased
      in Group B rats as compared to Group A rats, and decreased in Group C rats as
      compared to Group B rats. The activities of CAT increased in Group C as compared
      to Group B rats. The number of apoptotic neurons in the prefrontal cortex was
      lower in Group C as compared to Group B rats.

PMID- 18612762
TI  - Long-term survival and outcome after first stroke in the Sicilian Aeolian Island
      Archipelago population.
AB  - BACKGROUND: Only a restricted number of population studies based on long-term
      prognosis after a stroke have been published. We analyzed long-term survival and
      outcome in insular first-ever stroke population from the Aeolian Archipelago.
      SUBJECTS AND METHODS: From 1 July, 1999 to 30 June 2002, 62 patients with first
      ever stroke were recruited to evaluate short-term incidence and outcome.
      Information for every patient was collected by phone interviews after 3 months, 1
      year, and 4 years. RESULTS: 30 days case fatality rate was 24.2% (95% C.I. 14.22
      to 36.75). Fifty-one percent (95% C.I. 35.8 to 66.3) of patients died before last
      survey and 39.1% died during the first year of follow-up. Annual approximate
      death risk amounted to about 10%. The cerebrovascular causes were the most
      frequent causes of death (65.2%). A high level of invalidity at 4 years was
      present in many survivors (40%). None of the deceased had followed physio
      kinesitherapy, or applied for equipment or services. CONCLUSION: More attentive
      medical care for stroke patients could help improve outcome, reducing mortality
      for patients from the Aeolian island, who already showed a low incidence.

PMID- 18612764
TI  - A case of posterior reversible encephalopathy during polyarteritis nodosa
      vasculitis.
AB  - Posterior reversible encephalopathy is a distinctive syndrome associated with
      different diseases and drugs. Disease evolution is frequently favorable with an
      adequate treatment. Damage typically involves parietal-occipital lobes even if a
      more anterior diffusion has been described. Here, we report the case of a woman
      affected by Polyarteritis Nodosa, who suddenly complicated with decreased
      consciousness and seizures, during an acute hypertensive state. MRI imaging
      showed increased T2 and FLAIR signal in posterior regions. Her neurological
      evolution was positive, according to arterial pressure correction, although the
      systemic vasculitis was still ongoing, hence affecting final prognosis.

PMID- 18612763
TI  - Relationship between clinical examination, quality of life, disability and
      depression in CMT patients: Italian multicenter study.
AB  - OBJECTIVE: To assess which are the clinical examination tests that are more
      related to quality of life (QoL), depression, and disability in CMT patients.
      DESIGN: Large prospective multicenter study through the use of validated
      clinical, disability, and QoL measurements. Correlations between clinical pattern
      and disability/QoL and depression were studied. SETTING: Departments of
      Neurology. PATIENTS AND PARTICIPANTS: 211 CMT patients (60% females, mean age
      42.5 years). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Sensory function was
      related to both mental and physical aspects of patient's QoL. Ability to walk on
      toes and heels was related to physical aspects of QoL/disability but also to
      bodily pain. Strength of forearm/hand intrinsic muscles was related to disability
      and physical aspects of QoL. CONCLUSIONS: Some clinical tests may be better
      outcome measures than others because they are related to aspects of life highly
      relevant to the patients. This information may be useful in clinical practice and
      in clinical trials to infer the patient's QoL.

PMID- 18612765
TI  - Paradoxical brain embolism in a young man with isolated pulmonary arteriovenous
      fistula.
AB  - We herein report a case of ischemic stroke due to paradoxical brain embolism in a
      young man, a trumpet player. Extensive diagnostic investigations revealed the
      presence of an isolated pulmonary arteriovenous fistula as the only risk factor
      for stroke. The peculiarity of this case is the early onset of neurological
      symptoms in the absence of Hereditary Hemorrhagic Teleangiectasia. The Authors
      suppose the repeated Valsalva maneuvers as a possible factor promoting fistula
      enlargement and symptoms development.

PMID- 18612766
TI  - Non-manifesting Refsum heterozygotes carrying the c.135-2A>G PAHX gene
      transition.
AB  - So far, subjects heterozygous for PAHX mutations are regarded as non-symptomatic.
      In the 24-year-old, HIV-negative daughter and the 26-year-old, HIV-negative son
      of a patient with Refsum disease due to the homozygous c.135-2A>G transition at
      the splice site before exon 3 of the PAHX gene, slight abnormalities suggestive
      of the disease became apparent. The daughter reported a single fever cramp in
      childhood, recurrent, short-lived amaurotic episodes after getting up from
      supine, short-sightedness, hypoacusis, and restless legs. The son complained
      about restless legs, hyperhidrosis, hypoacusis, and bulbar oscillations. Though
      both children carried the same mutation as their mother in the heterozygous form,
      clinical neurologic examination, nerve conduction studies and serum phytanic acid
      concentration were normal in both of them, implying that the described
      abnormalities were not causally related to the PAHX mutation. In the absence of
      elevated phytanic acid concentrations, clinical neurologic abnormalities in
      heterozygous relatives of Refsum patients are not attributable to heterozygosity
      for PAHX mutations.

PMID- 18612767
TI  - Electrophysiological findings in a case of congenital lower limb hypoplasia.
AB  - Limb hypoplasia is a rare congenital disorder. Is usually encountered in patients
      with segmental spinal dysplasia (SSD), in progressive facial hemiatrophy (Parry
      Romberg syndrome) and in other rare conditions. We performed an extensive
      electrophysiological study in a 18-year-old female with congenital left lower
      limb hypoplasia, but with no motor and sensory deficit. Electrophysiological
      investigation comprised motor and sensory nerve conduction velocities, needle
      EMG, quantitative sensory studies and SEP with standard techniques. The study
      showed markedly involved large diameter peripheral sensory nerve fibers and
      intact motor and small diameter peripheral sensory nerve fibers. Extensive
      electrophysiological investigation in cases of limb hypoplasia has not been
      previously performed. In this patient congentital hypoplasia of the muscles also
      involved the peripheral large diameter sensory nerve fibers.

PMID- 18612768
TI  - Acute Akinesia, an unusual complication in Parkinson's Disease: a case report.
AB  - Acute akinesia (AA) is a rare but serious complication of Parkinson's Disease
      (PD) 0,3% of all patients with PD). It can be related to infectious condition,
      surgery, or treatment changes. AA can completely recover or result in some motor
      deficits, and, in the most severe forms, it may lead to untreatable complications
      and death. Here we report the case of a 67-year-old man with PD who rapidly
      developed a severe akinetic state with rise of temperature (39 degrees C) and
      creatine phosphokinase concentration (up to 5000 mg/dL). After excluding
      infection diseases and other pathologies, we suspected AA and added apomorphine
      50mg/die s.c. and ondansetron 8 mg i.v. The patient responded to treatment and
      ameliorated in few weeks.

PMID- 18612769
TI  - Acute myeloid leukemia induced by mitoxantrone treatment for aggressive multiple
      sclerosis.
AB  - Acute myeloid leukemia (t-AML) is one of the worst adverse events of mitoxantrone
      treatment, but the exact risk in multiple sclerosis (MS) patients is not yet
      known. We describe a case wherein the patient developed t-AML 11 months after
      mitoxantrone had been discontinued. The patient was treated by polychemotherapy
      and autologous bone marrow transplantation with complete recovery of t-AML and
      stabilization of the neurological disease.

PMID- 18612770
TI  - The first Italian family with evidence of pyramidal impairment as phenotypic
      manifestation of Silver syndrome BSCL2 gene mutation.
AB  - Silver syndrome (SPG17) is a rare form of hereditary spastic paraparesis. Its
      relationship to distal hereditary motor neuropathy (dHMN) type V is underlined by
      the recent discovery of causative mutation in BSCL2 gene coding for a protein
      termed seipin, an integral membrane protein of endoplasmic reticulum, with
      unknown function. Here we report the third Italian family with dHMN and SPG17 in
      which two affected members harbor the heterozygous N88S mutation in the BSCL2
      gene. The proband developed a severe paraparetic spastic gait, while, in the
      other Italian families reported so far, no signs of upper motor neuron
      involvement were observed. This family confirms the clinical heterogeneity
      associated with this specific mutation. Moreover, this is the first report in
      which neuroimaging seems to confirm the pyramidal alterations in dHMN associated
      to SPG17.

PMID- 18612771
TI  - Charcot-Marie-Tooth and pain: correlations with neurophysiological, clinical, and
      disability findings.
AB  - Pain is not considered a relevant symptom in Charcot-Marie-Tooth (CMT) patients
      and no studies have comprehensively assessed it. We performed a multidimensional
      assessment in 211 consecutive CMT patients to evaluate the clinical features,
      quality of life (QoL) and disability. For QoL we used the SF-36, which comprises
      one domain called "Bodily Pain" (BP), which is a generic measure of intensity of
      pain. Results showed that pain is a relevant symptom related to gender, CMT
      subtypes, clinical picture, disability, and mildly to neurophysiological
      impairment. In our study the importance of pain was an occasional finding.
      Because of the study design we are not able to ascertain if pain is primarily due
      to the neuropathy or if it is due to the muscoloskeletal deformities arising as a
      consequence of the neuropathy. Our study underlined that pain should be
      considered as a relevant symptom in CMT patients and further studies should be
      performed.

PMID- 18612774
TI  - The Radiological Medical Act approved by the SIRM Executive Committee on July 2,
      2007.

PMID- 18612773
TI  - Education and professionalism of the radiologist in a constantly evolving
      society.

PMID- 18612775
TI  - Highlights at the gate of tryptophan catabolism: a review on the mechanisms of
      activation and regulation of indoleamine 2,3-dioxygenase (IDO), a novel target in
      cancer disease.
AB  - Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and rate-limiting step of
      Kynurenine pathway along the major route of Tryptophan catabolism. The scientific
      interest in the enzyme has been growing since the observations of the involvement
      of IDO in the mechanisms of immune tolerance and in the mechanisms of tumor
      immuno-editing process. In view of this latter observation, in particular,
      preclinical studies of small molecule inhibitors of the enzyme have indicated the
      feasibility to thwart the immuno-editing process and to enhance the efficacy of
      current chemotherapeutic agents, supporting the notion that IDO is a novel target
      in cancer disease.This review covers the structural and conformational aspects of
      substrate recognition by IDO, including the catalytic mechanism and the so-far
      puzzling mechanisms of enzyme activation. Furthermore, we discuss the recent
      advances of medicinal chemistry in the field of IDO inhibitors.

PMID- 18612776
TI  - Chromatographic separation of enantiomers of non-protein alpha-amino acids after
      derivatization with Marfey's reagent and its four variants.
AB  - Some non-protein alpha-amino acids were derivatized with 1-fluoro-2,4
      dinitrophenyl-5-L-alaninamide (Marfey's reagent, MR, FDNP-L-Ala-NH(2),) and four
      of its structural variants FDNP-L-Phe-NH(2), FDNP-L-Val-NH(2), FDNP-L-Leu-NH(2)
      and FDNP-L-Pro-NH(2). The resultant diastereomers were separated by normal and
      reversed phase thin layer chromatography (TLC) and reversed phase HPLC. In normal
      phase TLC, best resolution was obtained with solvent combination of phenol-water
      (3:1) while in reversed phase TLC mixtures of acetonitrile with triethylammonium
      phosphate buffer were found successful for resolution of diastereomers. The
      separation behavior of diastereomers prepared with different reagents was
      compared. The diastereomers of most of the amino acids prepared with FDNP-L-Leu
      NH(2) were best separated while those prepared with FDNP-L-Pro-NH(2) failed to
      separate in most of the cases. The diastereomers were also separated on a
      reversed phase C(8) column with gradient elution using mixture of aqueous
      trifluoroacetic acid (TFA) and acetonitrile and with detection at 340 nm. The
      effects of TFA concentration, flow rate and run time on HPLC separation were
      studied.

PMID- 18612777
TI  - TIG3: a regulator of type I transglutaminase activity in epidermis.
AB  - Keratinocytes undergo a process of terminal cell differentiation that results in
      the construction of a multilayered epithelium designed to produce a structure
      that functions to protect the body from dehydration, abrasion and infection.
      These protective properties are due to the production of a crosslinked layer of
      protein called the cornified envelope. Type I transglutaminase (TG1), an enzyme
      that catalyzes the formation of epsilon-(gamma-glutamyl)lysine bonds, is the key
      protein responsible for generation of the crosslinks. The mechanisms that lead to
      activation of transglutaminase during terminal differentiation are not well
      understood. We have identified a protein that interacts with TG1 and regulates
      its activity. This protein, tazarotene-induced gene 3 (TIG3), is expressed in the
      differentiated layers of the epidermis and its expression is associated with
      transglutaminase activation and cornified envelope formation. We describe a novel
      mechanism whereby TIG3 regulates TG1 activity.

PMID- 18612778
TI  - Megakaryopoiesis and platelet function in polycythemia vera and essential
      thrombocythemia patients with JAK2 V617F mutation.
AB  - Patients with Ph chromosome negative myeloproliferative disease (Ph-MPD) have an
      increased risk of vascular complications. It remains controversial whether
      patients with the JAK2 V617F mutation (V617F) exhibit increased risk, while
      recent growing evidence has shown a critical role for V617F in clonal
      erythropoiesis in Ph-MPD. We studied 53 patients with Ph-MPD especially in
      relation to megakaryopoiesis, the thrombotic complications and the presence of
      V617F. Using novel mutation-specific PCR which is a highly sensitive PCR-based
      assay for detection of JAK2 mutated allele(s), we identified V617F in 38 Ph-MPD,
      which include 13 polycythemia vera (PV), 23 essential thrombocythemia (ET) and 2
      chronic idiopatic myelofibrosis. The numbers of megakaryocytes were significantly
      increased in PV and ET patients with V617F, but the platelet counts were slightly
      lower. Although statistically not significant, the incidence of thrombotic events
      was higher in the group with V617F compared to in those without the mutation.
      Agonist-induced in vitro platelet aggregation and platelet adhesion were not
      affected by the presence of this mutation. Nonetheless, we found a
      hypercoagulable state in Ph-CMPD with V617F by employing whole blood
      thromboelastography. It suggests pre-thrombotic tendencies in CMPD are complex
      and JAK2 V617F mutation might have a role in vivo blood coagulation by altering
      not only the number, but function(s) of all three myeloid cells, including red
      blood cells, white blood cells and platelets in Ph-CMPD.

PMID- 18612779
TI  - Epidermal nevus syndrome with hypophosphatemic renal rickets with hypercalciuria:
      a bonemarrow diagnosis.

PMID- 18612780
TI  - Perioperative host-tumor inflammatory interactions: a potential trigger for
      disease recurrence following a curative resection for colorectal cancer.
AB  - The aim of the present review was to investigate whether host-tumor interactions
      are causal or consecutive clinical factors associated with surgical stress that
      influence the long-term survival after a curative resection of colorectal cancer.
      A Medline/PubMed search was conducted to identify the relevant articles
      investigating the factors related to surgical stress and their effects on the
      long-term survival after a curative resection of colorectal cancer. The
      intraoperative state is defined as a cytokine storm in which ongoing local
      cytokine production occurs at the site of the tumor, thus further enhancing the
      autocrine cytokine loop for angiogenic factor production. The postoperative state
      is defined as tissue regeneration in which surgery-related clinical events
      enhance the systemic induction of inflammatory cytokines, which in turn
      synergistically exaggerate the local activation of tumor growth factors. Host
      tumor interactions under surgical stress may act synergistically as potent tumor
      growth factors, and may thus influence long-term survival. Controlling surgical
      insults and/or regulating perioperative inflammatory responses may therefore lead
      to new therapeutic approaches for controlling disease recurrence.

PMID- 18612781
TI  - Sentinel lymph node biopsy after neoadjuvant chemotherapy in a patient with
      operable breast cancer.
AB  - PURPOSE: This study was undertaken to assess the feasibility of performing a
      sentinel lymph node biopsy (SLNB) for a patient with operable breast cancer after
      undergoing neoadjuvant chemotherapy (NAC). METHOD: Between January 2002 and
      December 2003, women with primary breast cancer who had a breast tumor measuring
      larger than 3 cm in unilateral diameter were eligible for NAC. All patients who
      had completed NAC underwent lymphatic mapping with labeled (99m)Tc phytate on the
      day before surgery. Sentinel lymph node biopsy followed by a full axillary lymph
      node (AXLN) dissection (ALND) was performed in all patients. Sentinel lymph nodes
      (SLN) were sent for a frozen-section examination. RESULTS: The rate of SLN
      identification was 71%. Both the sensitivity and negative predictive value of
      SLNB were 100%. The false negative rate was 0%. When candidates for SLNB were
      restricted to patients with a breast tumor measuring less than 3 cm and
      clinically negative nodes after NAC, the rate of SLN identification increased to
      93% from 71% while still maintaining the 0% false negative rate. CONCLUSION:
      Sentinel lymph node biopsy after NAC is therefore considered to be a feasible and
      accurate method to predict the AXLN status in patients who have a breast tumor
      measuring less than 3 cm in unilateral diameter and a clinically negative AXLN
      status at the time of surgery after NAC.

PMID- 18612782
TI  - Simultaneous open-heart surgery and pectus deformity correction.
AB  - PURPOSE: Pectus deformities and cardiac problems sometimes require simultaneous
      surgery. We report our experience of performing this surgery and review the
      relevant literature. METHODS: We performed simultaneous pectus deformity
      correction and open-heart surgery in six patients between 1999 and 2006. The
      pectus deformities were pectus carinatum in one patient and pectus excavatum in
      five patients. The cardiac problems were coronary artery disease in one patient,
      an atrioseptal defect (ASD) with a ventricular septal defect (VSD) in one, a VSD
      in one, mitral valve insufficiency with left atrial dilatation in one, and an
      ascending aortic aneurysm with aortic valve insufficiency caused by Marfan's
      syndrome in two. We corrected the pectus deformities using the modified Ravitch's
      sternoplasty in all patients. First, while the patient was supine, we resected
      the costal cartilage; then, after completing the cardiac surgery, the sternum was
      closed and the additional time required for the pectus operation was calculated
      for each patient. Patients were examined 1, 4, and 6 months postoperatively.
      RESULTS: The average operation time was 102 min, and there were no major
      complications. The pectus bars were removed 4-6 months postoperatively. Good
      cardiac and cosmetic results were achieved in all patients, who were followed up
      for 5 years. CONCLUSIONS: Concomitant pectus deformity correction and open-heart
      surgery can be performed safely, eliminating the risks of a second operation in a
      staged procedure.

PMID- 18612783
TI  - Preoperative elevation of serum C-reactive protein as an independent prognostic
      indicator of colorectal carcinoma.
AB  - PURPOSE: The preoperative elevation of serum C-reactive protein (CRP) is thought
      to be a prognosticator of carcinomas of the digestive tract. We conducted this
      study to investigate the clinical importance of the preoperative elevation of
      serum CRP in patients with colorectal carcinoma (CRC). METHODS: We investigated
      the correlation between an elevated preoperative serum CRP level and the
      clinicopathologic factors, including prognosis, of 116 patients who underwent
      resection of CRC. RESULTS: Forty-seven (40.5%) patients had an elevated serum CRP
      value preoperatively (group H) and 69 (59.5%) did not (group L). There were
      significant differences in the tumor size, proportion of poorly differentiated
      tumors, depth of invasion, lymph node metastasis, lymphatic invasion, and tumor
      stage between the two groups. Survival was significantly lower in group H than in
      group L (P < 0.0001). Multivariate analysis showed that the preoperative
      elevation of serum CRP (P = 0.0007), as well as poor differentiation (P = 0.027)
      and advanced tumor stage (P = 0.007) were independent prognostic factors in
      patients with CRC. CONCLUSION: We found the preoperative elevation of serum CRP
      to be an independent prognostic indicator of CRC.

PMID- 18612784
TI  - Early experience of performing a modified Kugel hernia repair with local
      anesthesia.
AB  - PURPOSE: We report our results with the modified Kugel hernia repair, a
      relatively new and minimally invasive open technique offering the advantages of
      preperitoneal repair without the need for general anesthesia. METHODS: We
      performed 42 inguinal or femoral hernias (44 sides), including incarcerated
      femoral hernias, using this modified technique, giving the patient local
      anesthesia with very little sedation. We describe the operative techniques used
      and the postoperative complications encountered. RESULTS: The mean operation time
      was 55 +/- 26 min and the mean hospital stay was 4 days (2-8 days). There were no
      major postoperative complications and patients were followed up for a mean period
      of 1 year. Only one patient complained of mild discomfort in the inguinal area
      after 6 months. There was no incidence of recurrence. CONCLUSION: The modified
      Kugel hernia repair is easy to learn, and it seems to have a lower recurrence
      rate and fewer postoperative complications than conventional types of hernia
      repair. Moreover, it offers the advantage of allowing the patient to undergo
      preperitoneal inguinal hernia repair under local anesthesia, which is especially
      beneficial for older patients with preoperative morbidity.

PMID- 18612785
TI  - Effectiveness of leukocytapheresis in suppressing the occurrence of surgical site
      infections following surgery for ulcerative colitis.
AB  - PURPOSE: Surgical site infections (SSIs) occur more frequently in surgery for
      patients with ulcerative colitis than in regular colon surgery. We report here on
      a joint study that was prospectively conducted by six facilities to verify that
      performing leukocytapheresis (LCAP) therapy immediately following surgery
      regulates neutrophil activity and acts to suppress the occurrence of SSIs.
      METHODS: LCAP was performed using Cellsorba EX with nafamostat mesilate as an
      anticoagulant; therapy was begun within 2 h postoperatively. Subjects were 143
      patients undergoing surgery in cases of ulcerative colitis (LCAP group, 40
      patients; control group, 103 patients). RESULTS: 1) With regard to the SSI
      incidence rate, SSIs occurred in 4 of 37 patients (10.8%) in the LCAP group
      overall, whereas they occurred in 29 of 103 patients (28.2%) in the control group
      overall; in the LCAP group, the occurrence of SSIs tended to be suppressed (P =
      0.069). With 2-stage surgery in particular, SSIs occurred in the LCAP group in 1
      of 28 patients (3.6%) and in the control group in 21 of 86 patients (24.4%); in
      the LCAP group, the occurrence of SSIs was significantly lower (P = 0.013). The
      length of postoperative hospitalization was 24.9 +/- 11.1 days for the 36
      patients in the LCAP group and 31.2 +/- 14.6 days for the 103 patients in the
      control group; the length was significantly reduced in the LCAP group (P =
      0.018). 2) From pre-surgery to day 1 of hospitalization, the granulocyte elastase
      level rose both in patients who experienced SSIs and in patients who did not
      experience them. It remained high in patients who experienced SSIs in comparison
      with patients who did not experience SSIs and was significantly higher prior to
      LCAP in particular. 3) While LCAP was being performed, there were adverse events
      in 5 of 40 patients (12.5%), but these were all transient; it was determined that
      LCAP presented no problems in terms of safety. CONCLUSION: LCAP therapy was
      effective in suppressing the occurrence of SSIs following 2-stage surgery for
      ulcerative colitis and also reduced the length of postoperative hospitalization.

PMID- 18612786
TI  - Wound infection after a laparoscopic resection for colorectal cancer.
AB  - PURPOSE: The aim of this study was to investigate whether the wound infection
      (WI) rate in laparoscopic surgery (LS) for colorectal cancer is lower than that
      in open surgery (OS), and to evaluate the influence of perioperative intravenous
      antibiotic prophylaxis on the development of WI in LS. METHODS: We performed a
      meta-analysis study comparing the WI rate in patients who underwent either OS or
      LS in randomized controlled trials (RCTs), with a relatively large number of
      registered patients. Moreover, a subgroup analysis of recently reported RCTs from
      Japan was performed, and 290 consecutive patients who underwent LS for colorectal
      cancer at our institution were evaluated for the influence of perioperative
      intravenous antibiotic prophylaxis on the development of WI. RESULTS: The WI rate
      of the LS group was significantly lower than that of the OS group in a meta
      analysis; however, no positive effect of the intra-and postoperative antibiotic
      prophylaxis on the development of WI was demonstrated. CONCLUSIONS: Laparoscopic
      surgery for colorectal cancer is considered a surgical technique that has a lower
      incidence of WI in comparison to OS. Well-designed prospective, randomized
      controlled trials should therefore be conducted to evaluate whether
      intraoperative repeated dosing or postoperative repeated dosing is effective in
      reducing WI in LS.

PMID- 18612787
TI  - Efficacy of a continuous venous infusion of fluorouracil and daily divided dose
      cisplatin as adjuvant therapy in resectable colorectal cancer: a prospective
      randomized trial.
AB  - PURPOSE: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator
      of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to
      compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected
      colorectal cancer as the adjuvant therapy. METHODS: One hundred and eighty-eight
      stage II or III colorectal cancer patients were enrolled. Patients were randomly
      assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5
      mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years)
      (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively
      (oral 5-FU arm). RESULTS: The 5-year disease-free survival (DFS) rates and the
      overall survival (OS) rates indicated no significant difference between the two
      arms. By stratified analysis, in the colon cancer patients, the DFS and the OS
      for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP
      arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P =
      0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in
      two arms. CONCLUSIONS: DDD-FP followed by oral 5-FU therapy suggested a feasible
      regimen for patients with resected colon cancer as the adjuvant therapy.

PMID- 18612788
TI  - Neurinoma originating from the recurrent nerve: report of a case.
AB  - Schwannoma is an uncommon, peripheral nerve sheath tumor of the neck that can
      occur either as an isolated lesion or multiple lesions. Multiple schwannomas, as
      seen in neurofibromatosis, occur less frequently. The rare occurrence and poorly
      defined symptoms of these tumors often make their preoperative diagnosis
      difficult. This report describes an unusual case of recurrent nerve Schwannoma
      which was successfully identified by color Doppler sonography.

PMID- 18612789
TI  - Localized malignant mesothelioma in the middle mediastinum: report of a case.
AB  - Localized malignant mesothelioma in the mediastinum is rare and most known cases
      have been reported as "localized malignant pericardial mesothelioma." We report a
      case of a middle mediastinal tumor, which we were able to resect completely.
      Histopathological examination of the tumor confirmed that it was a malignant
      epithelial lymphohistiocytoid mesothelioma. We assumed that the tumor was derived
      from the pericardium. Local recurrence was detected 1 year after resection, and
      the patient died of the disease about 2 years later.

PMID- 18612790
TI  - Lung cancer associated with Sweet's syndrome: report of a case.
AB  - Lung cancer associated with Sweet's syndrome is extremely rare. There are only
      seven reports of such cases. As far as could be determined from a comprehensive
      search, there is no reported operative case of lung cancer with this syndrome in
      the world literature. A 75-year-old Japanese man was diagnosed as having Sweet's
      syndrome. A chest computed tomography (CT) scan to screen for malignant lesions
      associated with this syndrome revealed an abnormal shadow in the lung. Although
      [(18)F]2-fluoro-2-deoxy-D: -glucose positron emission tomography showed no
      abnormal uptake, lung cancer was most strongly suspected by chest CT. His
      erythema improved rapidly with steroid therapy and he underwent a segmentectomy
      (S(6)) of the right lower lobe. A pathological examination revealed lung
      adenocarcinoma (pT1N0M0: Stage Ia). The patient was discharged from the hospital
      without any worsening of Sweet's syndrome. We herein report a first operative
      case of an early stage lung adenocarcinoma with this syndrome.

PMID- 18612791
TI  - Metastatic pulmonary leiomyosarcoma presenting with a long disease-free interval:
      report of a case.
AB  - The prognosis in patients with retroperitoneal leiomyosarcoma and its distant
      metastasis is poor. We herein present an extremely rare case of an 83-year-old
      woman with a pulmonary metastasis from retroperitoneal leiomyosarcoma. The
      disease-free interval between the resection of the primary tumor and the
      diagnosis of metastasis was longer than 23 years. She was successfully treated
      with a video-assisted thoracic surgery lobectomy.

PMID- 18612792
TI  - Primary esophageal diffuse large B-cell lymphoma: report of a case.
AB  - Primary esophageal lymphoma is very rare, with fewer than 25 cases documented in
      the English-language literature. We report a case of primary diffuse large B-cell
      lymphoma of the esophagus in a 42-year-old woman. Barium esophagogram revealed
      almost complete esophageal obstruction at the level of the cervical esophagus,
      and flexible endoscopy showed a circumferential submucosal tumor covered with
      intact mucosa. Neck magnetic resonance imaging (MRI) showed a wide cervical mass
      circumferentially encompassing the lumen of the cervical esophagus. Biopsies
      taken with multiple forceps during flexible and rigid esophagoscopy were
      nondiagnostic. Finally, external esophageal wall biopsies taken during neck
      exploration provided information that helped us establish the diagnosis.
      Pathohistological findings confirmed non-Hodgkin's lymphoma of the diffuse large
      B-cell type. The patient was treated with combined immunochemotherapy, consisting
      of rituximab plus cyclophosphamide, vincristine, adriablastin, and prednisone
      (CHOP), followed by irradiation. A complete response was achieved, and 3 years
      after diagnosis and treatment the patient was disease-free.

PMID- 18612793
TI  - Esophageal granular cell tumor covered by intramucosal squamous cell carcinoma:
      report of a case.
AB  - We report a case of a granular cell tumor (GCT) covered by squamous cell
      carcinoma (SCC) in the esophagus. A 69-year-old Japanese man was admitted to our
      hospital for treatment of superficial esophageal cancer detected by upper
      gastrointestinal endoscopy. Endoscopic examination revealed a shallow ulcer in
      the esophagus, 28-32 cm from the incisor teeth. The pathological findings of a
      biopsy of the lesion were moderately differentiated SCC. Thus, we performed
      partial esophagectomy with two-field (thoraco-abdominal) lymph node dissection.
      Microscopic examination of the surgical specimen revealed intraepithelial SCC
      with minimal invasion, and a GCT, 3 x 1 mm in size, in the submucosa just beneath
      the SCC. Cytoplasmic granules in the GCT were positive for periodic acid-Schiff.
      Immunohistochemically, the GCT was strongly positive for S-100 protein. To our
      knowledge, this is the first published report of a GCT covered by SCC in the
      esophagus.

PMID- 18612794
TI  - Portomesenteric venous gas in acute bowel ischemia: report of a case.
AB  - Portomesenteric venous gas and pneumatosis intestinalis (PI) are rare but
      important radiographic findings. They are usually discussed separately in the
      literature and little is known about the clinical importance of their combination
      in acute bowel ischemia. Abdominal computed tomography (CT) has proven useful for
      detecting subtle portomesenteric venous gas or PI in the early stages of acute
      bowel ischemia. Although the CT findings of either portomesenteric venous gas or
      PI as separate entities are not pathognomonic of bowel infarction, CT evidence of
      the combination of both these disorders is strongly associated with transmural
      bowel infarction, especially band-like pneumatosis. We report a case of
      portomesenteric venous gas combined with band-like pneumatosis, diagnosed based
      on CT evidence of both findings. We performed an emergency laparotomy for
      suspected acute bowel ischemia, which was confirmed by the operative findings.

PMID- 18612795
TI  - Laparoscopic treatment for small bowel obstruction: report of a case.
AB  - An unusual case of small bowel obstruction in a patient with "virgin abdomen" was
      successfully diagnosed and the localized pathology was elucidated by a computed
      tomography scan, and the case was successfully treated by laparoscopy.

PMID- 18612796
TI  - Intestinal schistosomiasis manifesting as colonic intussusception arising from a
      mucocele of the appendix: report of a case.
AB  - We report a case of intestinal schistosomiasis manifesting as colonic
      intussusception resulting from a mucocele of the appendix, caused by the
      obstruction of appendiceal outflow by schistosome egg-induced fibrosis. An 81
      year-old woman from China presented with a tender right iliac fossa mass and
      computed tomography (CT) showed intussusception in the ascending colon.
      Exploratory laparotomy confirmed an appendiceal mass causing intussusception of
      the cecum into the ascending colon, with the appendix as the lead point, and
      lymphnode enlargement. We performed a right hemicolectomy for the appendiceal
      tumor. However, histologic examination revealed schistosoma eggs within the
      mucosa, submucosa, muscularis propria, and subserosal fat of the appendix, cecum,
      and ascending colon, and lymph nodes. The absence of dysplasia in the appendiceal
      mucosa indicated that the mucocele had developed from fibrosis induced by
      schistosome eggs obstructing the luminal outflow of mucin. Postoperatively, the
      patient was given praziquantel and recovered well.

PMID- 18612797
TI  - Percutaneous transhepatic portal embolization for persistent bile leakage after
      hepatic resection: report of a case.
AB  - Bile leakage is a relatively common complication after hepatic resection. We
      report a case of intractable bile leakage after hepatectomy, which was
      successfully treated by percutaneous transhepatic portal embolization (PTPE). A
      58-year-old Japanese man underwent anterior resection of the rectum followed by
      central bisegmentectomy of the liver (S4 + S5 + S8) for rectal cancer with liver
      metastasis. Bile leakage from the cut surface of the posterior segment developed
      on postoperative day 2. Conservative management with simple drainage and ethanol
      injections into the fistula proved ineffective. Thus, we performed PTPE in the
      posterior portal branch to eliminate the production of bile from the posterior
      segment and to block the enterohepatic circulation to that segment. His post
      treatment course was uneventful and the bile leakage resolved immediately.

PMID- 18612798
TI  - Re-epithelialization after laser therapy of a stenotic artificial tracheal graft:
      a pilot experimental study.
AB  - Tracheal reconstruction is a challenging field of research for thoracic surgeons.
      Recent tracheal grafting studies report short observation times, which make it
      difficult to conclusively evaluate efficacy. Long-term studies examining the
      durability of artificial trachea strategies are needed. An ideal artificial
      trachea strategy would allow for no intervention following replacement, but this
      approach is presently infeasible. Today, interventional bronchoscopic techniques
      are widely accepted as a follow-up to airway problems after surgery. Our
      laboratory developed a semiconductor laser method for endobronchial treatment of
      stenotic implanted artificial trachea grafts. We herein report the results of a
      pilot study testing the endobronchial laser treatment in a canine model. The
      laser treatment yielded vigorous airway re-epithelialization on the graft from
      the native trachea.

PMID- 18612799
TI  - Temozolomide treatment does not affect topiramate and oxcarbazepine plasma
      concentrations in chronically treated patients with brain tumor-related epilepsy.
AB  - OBJECTIVE: Medical management of brain tumor-related epilepsy is complicated by
      interactions between antiepileptic and chemotherapeutic drugs. We studied the
      effect of temozolomide therapy on the disposition of the new antiepileptic drugs
      topiramate (TPM) or oxcarbazepine (OXC). METHODS: Fifteen patients chronically
      treated with TPM or OXC in monotherapy starting a chemotherapeutic treatment with
      temozolomide were enrolled in the study, of which ten were available for the
      final analyses. Blood samples were collected before temozolomide treatment
      (T(0)), at its end (T(7)) and after further 1-3 weeks (T(14)-T(28)). For each
      patient, more than one treatment cycle was studied. Topiramate and OXC mono-10
      hydroxy derivative (MHD) plasma concentrations were determined by hplc coupled
      with ion spray mass spectrometer (TPM) or ultraviolet (MHD) detection. RESULTS:
      Mean TPM concentrations were 5.4 +/- 2.4 microg/ml at T(0) vs. 5.5 +/- 2.4
      microg/ml at T(7) (n = 14), and 5.4 +/- 2.4 microg/ml at T(0) vs. 5.6 +/- 2.8
      microg/ml at T(14)-T(28) (n = 14). Mean MHD concentrations were 16.4 +/- 7.6
      microg at T(0) vs. 18.5 +/- 9.0 microg/ml at T(7) (n = 5), and 16.8 +/- 7.0
      microg/ml at T(0) vs. 18.0 +/- 8.7 microg/ml at T(14)-T(28) (n = 8) (all
      comparisons not statistically significant; Student's t-test for paired samples).
      CONCLUSION: Temozolomide treatment did not affect TPM plasma concentrations in
      chronically treated patients. Data for MHD in OXC-treated patients were similar,
      but, due to the small sample size, results should be interpreted cautiously.These
      findings confirm that TPM (and possibly OXC) are a reasonable choice of
      antiepileptic drug in patients with brain tumor-related epilepsy.

PMID- 18612800
TI  - CD133 identifies perivascular niches in grade II-IV astrocytomas.
AB  - The aim of the present study was to investigate the localization and distribution
      of the putative brain tumour stem cell marker CD133 in formalin fixed paraffin
      embedded astrocytomas. A retrospective analysis of 114 grade II, III and IV
      astrocytomas was undertaken. The immunohistochemical expression of CD133 in
      paraffin sections was analysed using morphometry. In all grades, CD133 was
      expressed on tumour and endothelial cells. Tumour cells were found in
      perivascular niches, as dispersed single cells and in pseudopalisade formations
      around necrosis. There was no correlation between the mean volume fraction of
      CD133(+) niches and all CD133(+) tumour cells and tumour grade. However, the
      volume fraction of CD133(+) blood vessels increased significantly from 0.4% in
      diffuse astrocytomas to 2.2% in glioblastomas. Neither of them was related to
      patient survival. Double immunofluorescence stainings showed that the CD133(+)
      niches both contained CD133(+) cells with and without co-expression of the
      intermediate filament protein marker nestin, and only few CD133(+)/MIB-1(+)
      proliferating cells were found. In conclusion, a CD133(+) perivascular stem cell
      like entity exists in astrocytomas. CD133(+) tumour vessels may play an important
      role in a brain tumour stem cell context, while CD133 alone does not appear to be
      a specific tumour stem cell marker related to patient survival.

PMID- 18612801
TI  - Ubiquitin over-expression promotes E6AP autodegradation and reactivation of the
      p53/MDM2 pathway in HeLa cells.
AB  - It has been established that intracellular ubiquitin pools are subject to
      regulatory constrains. Less certain is the mechanism by which the pool of
      conjugated ubiquitin shift in parallel with total ubiquitin, and how this type of
      regulation affects the flux of substrates through the pathway. In this study we
      demonstrate that ubiquitin over-expression promotes the destabilization of the
      ubiquitin protein ligase E6AP, by a mechanism involving self-ubiquitination, and
      the stabilization of p53. These results represent the very first evidence that
      the levels of a ubiquitin ligase can be regulated in vivo by ubiquitin abundance,
      supporting the idea that a strict interrelationship between pathway component
      activities and ubiquitin pool size exists. Interestingly, ubiquitin-induced p53
      accumulation did not induce cell-cycle arrest, suggesting that although
      fluctuations of the intracellular ubiquitin content may actively modulate the
      level of regulatory proteins, this event is not per se sufficient to elicit a
      cellular response in terms of proliferation.

PMID- 18612802
TI  - Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem
      cell recruitment to retinal neovascularization sites.
AB  - Ubiquitous protein kinase CK2 participates in a variety of key cellular
      functions. We have explored CK2 involvement in angiogenesis. As shown previously,
      CK2 inhibition reduced endothelial cell proliferation, survival and migration,
      tube formation, and secondary sprouting on Matrigel. Intraperitoneally
      administered CK2 inhibitors significantly reduced preretinal neovascularization
      in a mouse model of proliferative retinopathy. In this model, CK2 inhibitors had
      an additive effect with somatostatin analog, octreotide, resulting in marked dose
      reduction for the drug to achieve the same effect. CK2 inhibitors may thus emerge
      as potent future drugs aimed at inhibiting pathological angiogenesis.
      Immunostaining of the retina revealed predominant CK2 expression in astrocytes.
      In human diabetic retinas, mRNA levels of all CK2 subunits decreased, consistent
      with increased apoptosis. Importantly, a specific CK2 inhibitor prevented
      recruitment of bone marrow-derived hematopoietic stem cells to areas of retinal
      neovascularization. This may provide a novel mechanism of action of CK2
      inhibitors on newly forming vessels.

PMID- 18612803
TI  - Regulation of renal organic ion transporters in cisplatin-induced acute kidney
      injury and uremia in rats.
AB  - PURPOSE: The purpose of this study was to examine the regulation of renal organic
      ion transporters in cisplatin-induced acute kidney injury (AKI) and its relation
      with indoxyl sulfate (IS), a uremic toxin. METHODS: The IS concentrations in the
      serum and kidney were monitored by high-performance liquid chromatography. Uptake
      of p-aminohippuric acid, estrone-3-sulfate and tetraethylammonium were examined
      using renal slices. Real-time PCR and immunoblotting were performed to examine
      the mRNA and protein expression of rOATs, rOCTs and rMATE1 in the kidney,
      respectively. RESULTS: The serum and renal IS levels were markedly elevated in
      cisplatin-treated rats. However, this effect was largely reversed by
      administration of AST-120, an oral charcoal adsorbent. The functions of renal
      basolateral organic anion and cation transporters were reduced in cisplatin
      treated rats. The levels of mRNA and protein corresponding to rOAT1, rOAT3, rOCT2
      and rMATE1, but not rOCT1, were depressed in the kidney of cisplatin-treated
      rats. Administration of AST-120 to cisplatin-treated rats partially restored the
      function and expression level of these transporters. CONCLUSIONS: Cisplatin
      induced AKI causes down-regulation of renal organic ion transporters accompanied
      by accumulation of serum and renal IS. IS could be involved in the mechanism of
      down-regulation of rOAT1, rOAT3 and rMATE1 under cisplatin-induced AKI.

PMID- 18612804
TI  - Effects of taurine on aortic rings isolated from fructose-fed insulin resistance
      Sprague-Dawley rat are changed.
AB  - PURPOSE: To observe and compare the effect of taurine on contractions of aortic
      rings isolated from normal (NC) and insulin resistance (IR) Sprague-Dawley rats,
      and to explore its underlying mechanism(s). METHODS: The IR animal model was made
      by feeding rats with high fructose diet for 8 weeks. Aortic rings were isolated
      and suspended in a tissue bath, and tensions were recorded isometrically. The
      effects of taurine on provoked contractions of the rings were assessed in absence
      or presence of different potassium channel or NO-synthase inhibitors. RESULTS:
      Taurine (20-80 mM) concentration-dependently relaxed precontractions induced by
      KCl (30 mM) and phenylephrine (1 microM) in NC rings, but enhanced the
      precontractions in IR rings. Denudation of the endothelium and pretreatment with
      N(G)-nitro-L-arginine methylester ester (0.1 mM) reversed the contraction
      enhancement of taurine to relaxation in IR rings. Tetraethylammonium (10 mM)
      nearly abolished taurine-induced relaxation of NC rings, and augmented taurine
      induced contraction enhancement in IR rings. Iberiotoxin (100 nM) only augmented
      the contraction enhancement in IR rings. 4-Aminopyridine (1 mM), glibenclamide
      (10 microM) and indomethacin (10 muM) had no influence on the effect of taurine
      in both NC and IR rings. CONCLUSION: Taurine enhances contractions in IR aortic
      rings but relaxes the contractions in normal rat aortic ring; the enhancement is
      endothelium-dependent and the relaxation is endothelium-independent. TEA
      sensitive K(+) channel may be involved in these actions; BK(Ca) channel
      dysfunction and endothelium-derived substances may be related to the contraction
      enhancement induced by taurine in IR aorta.

PMID- 18612805
TI  - Effects of a modified milieu therapy intervention on the social communicative
      behaviors of young children with autism spectrum disorders.
AB  - The purpose of the current study was to evaluate the effectiveness of combining
      milieu therapy and functional communication training (FCT)] to replace aberrant
      behavior with functional communicative skills in 3 male preschool or elementary
      aged children with Autism Spectrum Disorders (ASD). Study activities were
      conducted in the natural environments of the participants and parents acted as
      change agents. A concurrent multiple baseline design across participants was used
      to evaluate the effectiveness of the modified milieu therapy intervention.
      Results indicate that aberrant behavior decreased concurrent with an increase in
      total percentage of communication responses (PCR). The children maintained
      communication and low rates of aberrant behavior, and generalized their
      communication from the home to the classroom. A discussion of limitations and
      future research directions is included.

PMID- 18612806
TI  - Phylogenic analysis of the M genes of influenza viruses isolated from free-flying
      water birds from their Northern Territory to Hokkaido, Japan.
AB  - During 2000-2007, 218 influenza viruses of 28 different combinations of HA (H1
      H13) and NA (N1-N9) subtypes were isolated from fecal samples of free-flying
      water birds at two distant lakes in Hokkaido, Japan. Phylogenic analysis of the
      matrix (M) genes of 67 strains, selected on the basis of their subtype
      combinations, revealed that A/duck/Hokkaido/W95/2006 (H10N8) was a reassortant
      whose M and NA genes [corrected] belonged to North American non-gull-avian and
      the other six [corrected] genes to Eurasian non-gull-avian lineages. The M genes
      of other 65 strains belonged to Eurasian non-gull-avian and the one to Eurasian
      gull lineages. The M genes of 65 strains were grouped into three different
      sublineages, indicating that influenza viruses circulating in different
      populations of free-flying water birds have evolved independently in nature.

PMID- 18612807
TI  - The association between anxiety sensitivity and atopy in adult asthmatics.
AB  - There is growing evidence linking psychological stress to atopic disease,
      particularly asthma. Anxiety sensitivity, which is the fear of anxiety-related
      symptoms, may be particularly important in the study of anxiety and atopic
      disease. The present study examined the association between atopy and anxiety
      sensitivity in adult asthmatics. A total of 217 asthma patients who had undergone
      standard pulmonary function and allergen skin prick testing were included.
      Participants completed the Anxiety Sensitivity Index, Penn State Worry
      Questionnaire, Type D Personality Scale-16 and Beck Depression Inventory-II on
      the day of their asthma clinic visit. Total Anxiety Sensitivity Index score was
      found to be significantly higher in atopic (M = 17.15, SE = .9) versus non-atopic
      (M = 12.68, SE = 1.5) asthmatics, independent of age, sex, smoking status, asthma
      severity, asthma duration, and anxiolytic medication use (F = 6.11, p = .014).
      There was no evidence for a significant association between any of the other
      questionnaire scores and atopic status.

PMID- 18612808
TI  - Racial differences in beliefs about the effectiveness and necessity of mental
      health treatment.
AB  - Members of racial/ethnic minority groups are less likely than Caucasians to
      access mental health services despite recent evidence of more favorable attitudes
      regarding treatment effectiveness. The present study explored this discrepancy by
      examining racial differences in beliefs about how the natural course and
      seriousness of mental illnesses relate to perceived treatment effectiveness. The
      analysis is based on a nationally representative sample of 583 Caucasian and 82
      African American participants in a vignette experiment about people living with
      mental illness. While African Americans were more likely than Caucasians to
      believe that mental health professionals could help individuals with
      schizophrenia and major depression, they were also more likely to believe mental
      health problems would improve on their own. This belief was unrelated to beliefs
      about treatment effectiveness. These findings suggest that a belief in treatment
      effectiveness may not increase service utilization among African Americans who
      are more likely to believe treatment is unnecessary.

PMID- 18612809
TI  - Keeping the spirit of community partnerships alive in the scale up of HIV/AIDS
      prevention: critical reflections on the roll out of DEBI (Diffusion of Effective
      Behavioral Interventions).
AB  - DEBI, or the Diffusion of Effective Behavioral Interventions is the largest
      centralized effort to diffuse evidence-based prevention science to fight HIV/AIDS
      in the United States. DEBI seeks to ensure that the most effective science-based
      prevention interventions are widely implemented across the country in community
      based organizations. Thus, this is a particularly timely juncture in which to
      critically reflect on the extent to which known principles of community
      collaboration have guided key processes associated with the DEBI rollout. We
      review the available evidence on how the dissemination of packaged interventions
      is necessary but not sufficient for ensuring the success of technology transfer.
      We consider additional principles that are vital for successful technology
      transfer, which were not central considerations in the rollout of the DEBI
      initiative. These issues are: (1) community perceptions of a top-down mode of
      dissemination; (2) the extent to which local innovations are being embraced,
      bolstered, or eliminated; and (3) contextual and methodological considerations
      that shape community preparedness. Consideration of these additional factors is
      necessary in order to effectively document, manage, and advance the science of
      dissemination and technology transfer in centralized prevention efforts within
      and outside of HIV/AIDS.

PMID- 18612810
TI  - Is PCR testing of sentinel lymph nodes ready for clinical application in breast
      cancer?

PMID- 18612811
TI  - Myc-oncogene inactivating effect by proline rich polypeptide (PRP-1) in
      chondrosarcoma JJ012 cells.
AB  - Proline rich polypeptide (PRP-1) produced by NPV and NSO cells is released into
      the general circulation and exerts its effect on the activity of immunocompetent
      and neuronal cells. PRP-1 is a unique regulator of hematopoiesis, stimulator of
      bone-marrow hematogenesis. Taking into consideration our preliminary data on
      antitumor and unique diverse biological properties of PRP-1 previously described
      by Galoyan et al., we proceeded with investigation of the PRP-1 effect on
      chondrosarcoma, the second most common malignancy in bone, which tends to be
      locally invasive and then metastatic. Currently it does not have any effective
      treatment and does not respond either to radiation or chemotherapy, leaving
      surgical resection as the only option. Our experimental results of PRP-1 action
      on human chondrosarcoma JJ012 cells demonstrated inactivation, abolishment of Myc
      oncogene activity usually upregulated in chondrosarcoma cells and other
      malignancies. The fact that addition of PRP-1 caused drastic inactivation of Myc
      luc response element to the control level in human chondrosarcoma JJ012 cell line
      prompts to investigate further this neuropeptides powerful antioncogenic
      potential, opening up possibilities to consider PRP-1 as a potential therapeutic
      tool for chondrosarcoma treatment.

PMID- 18612812
TI  - A prospective study of transsulfuration biomarkers in autistic disorders.
AB  - The goal of this study was to evaluate transsulfuration metabolites in
      participants diagnosed with autism spectrum disorders (ASDs). Transsulfuration
      metabolites, including: plasma reduced glutathione (GSH), plasma oxidized
      glutathione (GSSG), plasma cysteine, plasma taurine, plasma sulfate, and plasma
      free sulfate among participants diagnosed with ASDs (n = 38) in comparison to age
      matched neurotypical controls were prospectively evaluated. Testing was conducted
      using Vitamin Diagnostics, Inc. (CLIA-approved). Participants diagnosed with ASDs
      had significantly (P < 0.001) decreased plasma reduced GSH, plasma cysteine,
      plasma taurine, plasma sulfate, and plasma free sulfate relative to controls. By
      contrast, participants diagnosed with ASDs had significantly (P < 0.001)
      increased plasma GSSG relative to controls. The present observations are
      compatible with increased oxidative stress and a decreased detoxification
      capacity, particularly of mercury, in patients diagnosed with ASDs. Patients
      diagnosed with ASDs should be routinely tested to evaluate transsulfuration
      metabolites, and potential treatment protocols should be evaluated to potentially
      correct the transsulfuration abnormalities observed.

PMID- 18612813
TI  - Parkin expression profile in dopamine d3 receptor knock-out mice brains.
AB  - Patients affected by autosomic recessive juvenile parkinsonism (ARJP) exhibit
      parkin gene mutations with brain decrease in dopamine D2/D3 binding sites. To
      date, there are no data indicating whether the reduction in dopamine D3 receptors
      (DRD3) may be associated with the expression of specific parkin variants. In the
      present study we investigated parkin expression profile in DRD3 knock-out mice
      brains. RT-PCR analysis was performed to assess qualitative changes in parkin
      isoforms' distribution pattern and in exons' expression both in wild type
      controls and dopamine D3 receptor's knock-out mice. Real-time PCR was performed
      to quantify single exons mRNA. Results demonstrated that exons 1, 2, 4, 6, 7, 8,
      were more expressed in wild type compared to dopamine D3 receptor KO mice brains
      while some other (3, 9, 10) were lower expressed. The expression levels of exons
      5, 11 and 12 did not change in both animal groups. Our analysis was confirmed by
      western blot, which showed that parkin protein levels were influenced by the
      absence of DRD3.

PMID- 18612814
TI  - The effects of piroxicam in the attenuation of MPP+/MPTP toxicity in vitro and in
      vivo.
AB  - Several lines of evidence support the neuroprotective action of cyclooxygenase-2
      (COX-2) inhibitors in various models of Parkinson's disease (PD). In the current
      study, we investigated the neuroprotective properties of several COX inhibitors
      against 1-methyl-4-phenylpyridinium (MPP+) in neuroblastoma Neuro 2A (N-2A) cells
      in vitro and the protection against degeneration of substantia nigra pars
      compacta (SNc) dopaminergic (DA) neurons after the administration of 1-methyl 4
      phenyl 1,2,3,6-tetrahydropyridine (MPTP) in C57/BL6 male mice. The data obtained
      demonstrate a lack of protective effects observed by COX 1-2 inhibitors ibuprofen
      and acetylsalicylic acid against MPP+ toxicity in N-2A, where piroxicam was
      protective in a dose dependent manner (MPP+ control: 15 +/- 2% MPP+ piroxicam: 5
      mM 89 +/- 4%). The data also indicate a drop in mitochondrial oxygen (O(2))
      consumption and ATP during MPP+ toxicity with no restoration of mitochondrial
      function concurrent to a heightened concentration of somatic ATP during piroxicam
      rescue. These findings indicate that the neuroprotective effects of COX
      inhibitors against MPP+ are not consistent, but that piroxicam may work through
      an unique mechanism to propel anaerobic energy metabolism. On the other hand,
      using mice, piroxicam (20 mg/kg) was effective against MPTP-induced dopaminergic
      degeneration in the (SNc) and loss of locomotive function in mice. Administering
      a 3 day pre-treatment of piroxicam (20 mg/kg) was effective in antagonizing the
      losses in SNc tyrosine hydroxylase protein expression, SNc DA concentration and
      associated anomaly in ambulatory locomotor activity. It was concluded from these
      findings that piroxicam is unique among COX inhibitors in providing very
      significant neuroprotection against MPP+ in vitro and in vivo.

PMID- 18612815
TI  - Growth factors and steroid mediated regulation of cytoskeletal protein expression
      in serum-deprived primary astrocyte cultures.
AB  - In this research we aimed to investigate the interactions between growth factors
      (GFs) and dexamethasone (DEX) on cytoskeletal proteins GFAP and vimentin (VIM)
      expression under different experimental conditions. Condition I: 24 h
      pretreatment with bFGF, subsequent 72 h switching in serum-free medium (SFM) and
      final addition of GFs, alone or by two in the last 24 h, after a prolonged (60 h)
      DEX treatment. Condition II: 36 h pretreatment with DEX (with bFGF in the last 24
      h), followed by SFM for 60 h and final addition for 24 h with growth factors
      alone or two of them together. Western blot analysis data showed a marked GFAP
      expression in cultures submitted to Condition I comparing results to untreated or
      treated controls. VIM expression was instead significantly reduced after GFs
      addition in the last 24 h of 60 h DEX treatment, respect to control DEX
      pretreated ones. Referring data to untreated controls, VIM expression was
      significantly enhanced after GFs addition. GFAP showed also a significant
      increase in astrocytes submitted to Condition II, respect to untreated or treated
      control cultures. VIM expression was up and down regulated under Condition II.
      Collectively, our findings evidence an interactive dialogue between GFs and DEX
      in astroglial cultures, co-pretreated with DEX and bFGF, regulating cytoskeletal
      network under stressful conditions.

PMID- 18612817
TI  - Are 12 nodes needed to accurately stage T1 and T2 colon cancers?
AB  - Evaluation of 12 lymph nodes has been mandated to prevent colon cancer
      understaging. Given that the probability of node metastases is largely associated
      with T-stage, are <12 nodes substandard for T1 and T2 lesions? We evaluated if
      survival for T1 and T2 tumors varies by nodes examined. In SEER, 61,237 patients
      undergoing colon cancer resection were identified. For each T-stage, 5-year
      survival rates were compared for node-negative cancers by using stepwise node cut
      point comparisons (4 nodes, <4, etc.). Survival impact was determined by log-rank
      test and hazard regression. For T1 tumors, 4 nodes had 24% lower hazard of death
      compared to <4. For T2 tumors, 10 nodes had the biggest survival impact, 15%
      lower hazard of death. In conclusion, the number of nodes to stage T1 and T2
      lesions may be <12.

PMID- 18612816
TI  - Helicobacter pylori cagA status and peptic ulcer disease in Iran.
AB  - Helicobacter pylori contributes to the development of peptic ulcers and atrophic
      gastritis. Furthermore, H. pylori strains carrying the cagA gene are more
      virulent than cagA -negative strains and are associated with the development of
      gastric adenocarcinoma. The cagA gene is a putative H. pylori virulence factor of
      unknown function. The aim of this study was to determine the prevalence of the
      cagA gene among H. pylori isolates and its relationship with peptic ulcer disease
      in 128 Iranian patients. A total of 107 (83.6%) samples were positive, including
      40 (95%) of the 42 patients with duodenal ulcer, 43 (86%) of the 50 patients with
      gastric ulcer, and 24 (66.6%) of the 36 patients with gastritis. cagA was present
      in 32 (80%) of 40 strains from duodenal ulcer patients, 33 (77%) of 43 strains
      from gastric ulcer patients, and 11 (46%) of 24 from gastritis patients. We also
      attempted to investigate the subtypes of 3' region of cagA gene in H. pylori
      strains isolated from Iranian patients and their relation to H. pylori-associated
      gastroduodenal diseases. The PCR product of cagA positive strains obtained with
      primer set CAG1/CAG2 differed in size, varying from 642 to 651 bp (subtype A) in
      33 isolates to 756 bp (subtype B/D) in 13 isolates. This does not support the
      view that subtypes of the 3' region of cagA gene in H. pylori isolated from Iran
      correlate with the clinical outcomes of H. pylori, but colonization with cagA
      positive strains was significantly higher among duodenal ulcer than gastritis
      patients in Iran.

PMID- 18612818
TI  - Genetic recombinant expression and characterization of human augmenter of liver
      regeneration.
AB  - AIMS: To establish a highly effective prokaryotic recombinant expression system
      for human augmenter of liver regeneration (hALR) and to characterize the
      recombinant hALR both in vitro and in vivo. METHODS: ALR cDNA was synthesized and
      inserted into expression vector pET28a+, the recombinant plasmid was transformed
      into BL21, and expression of hALR was induced by IPTG. Recombinant hALR (rhALR)
      was purified by sequential detergent wash, enterokinase (EK) digestion, gel
      filtration, and chelating chromatography. The rhALR was identified by SDS-PAGE,
      immunoblotting, MALDI-TOF-MS, and N-terminal sequencer. Cell proliferative effect
      of rhALR on human hepatocytes was analyzed by MTT. The protective effect of rhALR
      on liver function was observed on CCl(4)-induced intoxicated mice. RESULTS:
      Recombinant expression plasmid of ALR [pET28(a+)-hALR] was confirmed by
      restriction enzyme digestion and DNA sequencing. The expressed rhALR constituted
      30% of total bacterial protein. Molecular weight was 15,029 for monomer and
      30,136 for dimer by mass determination. N-terminal was M-R-T-Q-Q, exactly the
      same as anticipated for hALR. The purified protein migrating at about 15 KD
      showed excellent antigenicity in immunoblotting. The rhALR also showed a strong
      stimulative effect on hepatocyte proliferation. ALT and AST levels, liver
      histological structure, as well as the survival rate of CCl(4)-intoxicated mice
      were significantly improved when rALR was administrated at 40 microg/kg or 200
      microg/kg. CONCLUSIONS: The rhALR is successfully expressed highly effectively
      with anticipated MW, N-terminal, and antigenicity. It could play an important
      role in relieving acute hepatic injury and hepatic failure by promoting hepatic
      cell proliferation and improving liver function in CCl(4)-intoxicated mice.

PMID- 18612819
TI  - Synergistic growth inhibitory effects of the dual endothelin-1 receptor
      antagonist bosentan on pancreatic stellate and cancer cells.
AB  - Pancreatic stellate cells (PSC) play a key role in pancreatic fibrosis.
      Activation of PSC occurs in response to pro-fibrogenic stimuli and is maintained
      by autocrine loops of mediators, such as endothelin (ET)-1. Here, we have
      evaluated effects of the dual ET receptor antagonist bosentan in models of
      pancreatic fibrogenesis and cancer. Cell culture studies revealed that PSC and
      DSL6A pancreatic cancer cells expressed both ET-1 and ET receptors. Bosentan
      efficiently inhibited proliferation of both cell types and collagen synthesis in
      PSC. Expression of the myofibroblastic marker alpha-smooth muscle actin,
      connective tissue growth factor, and ET-1 itself in PSC was reduced, while
      expression of matrix metalloproteinase-9 was enhanced. Like PSC, DSL6A cells
      secrete less ET-1 when cultured with bosentan. In a rat model of pancreatic
      fibrosis, chronic pancreatitis induced by dibutyltin dichloride, a tendency
      towards a diminished disease progression was observed in a subgroup of rats with
      less severe disease. Together, our results indicate that bosentan exerts
      antifibrotic and antitumor effects in vitro. Its efficiency in vivo warrants
      further investigation.

PMID- 18612820
TI  - Antibacterial action of selenium-enriched probiotics against pathogenic
      Escherichia coli.
AB  - The purpose of this study was to evaluate the inhibitory activity of selenium
      enriched probiotics against pathogenic Escherichia coli (E. coli) in vitro and in
      vivo. Escherichia coli was co-cultured in vitro with each probiotic strain
      individually, and a mixture of the four strains and its population was counted at
      various time points. We also collected a cell-free culture supernatant (CFCS) of
      each probiotic strain and the four-strain mix to examine their antibacterial
      activity, using the cylinder plate method. Results demonstrated that co-culture
      with probiotics significantly reduced the number of E. coli. The different sizes
      of the inhibition zones made by each CFCS proved that E. coli was inhibited by
      the metabolites of the probiotics. In vivo, Kunming mice were allocated to
      different groups supplemented with selenium-enriched and other probiotics. After
      28 days, the mice were inoculated with pathogenic E. coli so that we could
      compare mortality rates and inspect other indexes of each treatment. The
      mortality of the group with selenium-enriched probiotics was the lowest. In
      addition, the organic antioxidant status improved, immunity was fortified, and
      the internal environment of the intestinal tract was enhanced with selenium
      enriched probiotic supplementation. In conclusion, selenium-enriched probiotics
      can strongly antagonize pathogenic E. coli in vitro and in vivo.

PMID- 18612821
TI  - CT colonography can be an adjunct to optical colonoscopy in CRC screening.
AB  - CT colonography or virtual colonoscopy is a fairly new modality that has the
      potential to play a significant role in screening for colon cancer. CT
      colonography is an attractive option for two specific reasons. First, it is non
      invasive and, second, it obviates the need for sedation. It thus overcomes the
      two major drawbacks of optical colonoscopy. CT colonography cannot be a stand
      alone technique for colorectal cancer screening because, unlike conventional
      colonoscopy, it does not possess a therapeutic option or a definite diagnostic
      capability. However, CT colonography can be a cost-effective complement to
      traditional colonoscopy if it is reasonably priced and if appropriate cut-off
      levels (>6 mm polyp) are used to increase its sensitivity.

PMID- 18612822
TI  - The effect of Saccharomyces boulardii on human colon cells and inflammation in
      rats with trinitrobenzene sulfonic acid-induced colitis.
AB  - Saccharomyces boulardii (S. boulardii) has beneficial effects in the treatment of
      intestinal inflammation; however, little is known about the mechanisms by which
      these effects occur. We investigated the effects of S. boulardii on the
      expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and
      interleukin-8 (IL-8), using human HT-29 colonocytes and a rat model of
      trinitrobenzene sulfonic acid (TNBS)-induced colitis. The effect of S. boulardii
      on gene expression was assessed by semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR), and Northern blot and Western blot assays.
      Pharmacological inhibitors for various signaling pathways were used to determine
      the signaling pathways implicated in the S. boulardii regulation of PPAR-gamma
      and IL-8. We found that S. boulardii up-regulated and down-regulated PPAR-gamma
      and IL-8 expression at the transcription level, both in vitro and in vivo (P <
      0.05, respectively). Saccharomyces boulardii blocked tumor necrosis factor-alpha
      (TNF-alpha) regulation of PPAR-gamma and IL-8 through disruption of TNF-alpha
      mediated nuclear factor kappa B (NF-kappaB) activation. Furthermore, S. boulardii
      suppressed colitis and expression of pro-inflammatory cytokine genes in vivo (P <
      0.05, respectively). Our study demonstrated that S. boulardii reduces colonic
      inflammation and regulates inflammatory gene expression.

PMID- 18612823
TI  - Ginkgo biloba (EGb 761) extract: effects on the myenteric plexus of the large
      intestine in Wistar rats.
AB  - The objective of this study was to evaluate the effect of the purified extract of
      the Ginkgo biloba (EGb 761) plant on the myenteric plexus in the proximal and
      distal colon of Wistar rats for a period of 120 days. The experimental rats were
      divided into two age groups: a young group, sacrificed at age 90 days, and an
      adult group, sacrificed at age 210 days. We observed a significant reduction in
      the number of neurons in the myenteric plexus of the adult group compared to the
      young group in both of the segments studied (P < 0.01). The adult group treated
      with Ginkgo biloba showed a significant increase in neuronal profile area in both
      the segments studied (P < 0.001). It can be concluded from these results that
      treatment with the purified Ginkgo biloba (EGb 761) plant extract at a dose of 50
      mg/kg body weight has neurotrophic effect on the myenteric plexus in the proximal
      and distal colon of rats after 120 days of treatment.

PMID- 18612824
TI  - Aspirin-induced mucosal cell death in human gastric cells: role of a caspase
      independent mechanism.
AB  - Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used
      for the treatment of pain and inflammation. Their use may result in
      gastroduodenal side effects, such as gastric irritation and ulcer formation.
      Although various strategies have been employed to minimize these adverse effects
      induced by NSAIDs, effective therapeutic targeting of this problem has been
      prevented by an incomplete understanding of the mechanisms underlying their
      pathogenesis. This study was undertaken to determine the role that non-caspase
      mediated apoptosis plays in inducing cellular injury and death in gastric mucosa
      exposed to aspirin. We proposed that the responsible mechanism was through
      mitochondrial failure, increased mitochondrial membrane permeability, and
      translocation of the intramitochondrial protein apoptosis-inducing factor (AIF).
      Human gastric adenocarcinoma mucosal cells (AGS cells) received no pretreatment
      or were preincubated with caspase inhibitors for 30 min. Cells were then treated
      with 40 mM aspirin for 2-4 h. Apoptosis was assessed by measuring the DNA-histone
      complex formation. Cell viability was determined by an acridine orange-ethidium
      bromide (EtBr) assay. The activation of AIF was evaluated by both Western
      blotting of the cytosol and mitochondrial extracts as well as by visualization
      and staining using fluorescence microscopy. Results showed that caspase inhibitor
      preincubation decreased DNA-histone complex formation when compared to aspirin
      treatment alone. Based on light microscope visualization, however, we determined
      that caspase inhibitor preincubation was unable to prevent AGS cell damage and
      death. These findings were confirmed by the acridine orange-EtBr test, which
      showed decreased cell viability with caspase inhibitor preincubation and aspirin
      treatment. We then tested whether non-caspase-mediated cell death occurred
      through an AIF mitochondrial pathway using Western blotting and fluorescence
      microscopy to determine AIF activation. The results showed that untreated cells
      had AIF localized to the mitochondria and cytosol. With 40 mM ASA at 4 h,
      translocation of AIF from the mitochondria to the nucleus occurred, showing
      activation. Caspase inhibition with z-VAD was unable to prevent AIF localization
      to the nucleus and subsequently unable to prevent cell death. Our results
      indicate that ASA in the presence of caspase inhibitors causes gastric mucosal
      cell death through a caspase-independent pathway suggestive of apoptosis-like
      programmed cell death. Effective therapeutic targeting of aspirin-induced
      apoptosis likely requires inhibition of both mitochondrial and caspase-mediated
      pathways.

PMID- 18612826
TI  - Adaptive neuro-fuzzy inference system for classification of ACL-ruptured knees
      using arthrometric data.
AB  - A new approach, based on Adaptive-Network-based Fuzzy Inference System (ANFIS),
      is presented for the classification of arthrometric data of normal/ACL-ruptured
      knees, considering the insufficiency of existing criteria. An ANFIS classifier
      was developed and tested on a total of 4800 arthrometric data points collected
      from 40 normal and 40 injured subjects. The system consisted of 5 layers and 8
      rules, based on the results of subtractive data clustering, and trained using the
      hybrid algorithm method. The performance of the system was evaluated in four
      runs, in the framework of a 4-fold cross validation algorithm. The results
      indicated a definite correct diagnosis for typical injured and normal cases.
      Except for two, all cases with marginally distinct force-displacement curves were
      also diagnosed correctly. The overall sensitivity and specificity of the system
      in four runs were 95.5% and 100%, respectively. The superior performance of the
      ANFIS classifier over previously suggested criteria highlights its capability
      when dealing with marginal arthrometric data of knees with partially disrupted
      ACL or hypermobility syndrome.

PMID- 18612825
TI  - Psychosocial correlates of overweight or obese status in Latino adults with
      coronary artery disease.
AB  - This study evaluated the psychosocial correlates of being overweight or obese
      among US born and immigrant Latino adults. Depressive symptoms were measured with
      the Center for Epidemiological Studies Depression Scale (CES-D10). Of the 177
      participants, 64% were either overweight or obese, of which, 51% also had
      comorbid depressive symptoms. On bivariate analyses, these participants were
      younger (OR = 2.4, 95% CI = 1.5-5.2), female (OR = 2.5, 95% CI = 1.3-4.6), US
      born (OR = 6, 95% CI = 1.3-9.0), more likely to have lived in the US 15 or more
      years (OR = 2.6, 95% CI 1.3-5.1), reported fair or poor health, (OR = 3.8, 95% CI
      = 1.8-8.0), and were more likely to perceive greater stress (OR = 7.8, 95% CI =
      3.4-18.0). On multivariate analysis, only perceived stress remained significant
      (OR = 6.5, 95% CI = 2.7-15.6). This suggests that interventions designed to
      reduce the epidemic of overweight and obesity in Latino adults may also need to
      address their psychosocial health.

PMID- 18612827
TI  - Bioengineering and imaging research opportunities workshop V: a summary.
AB  - The fifth Bioengineering and Imaging Research Opportunities Workshop (BIROW V)
      was held on January 18-19, 2008. As with previous BIROW meetings, the purpose of
      BIROW V was to identify and characterize research and engineering opportunities
      in biomedical engineering and imaging. The topic of this BIROW meeting was
      Imaging and Characterizing Structure and Function in Native and Engineered
      Tissues. Under this topic, four areas were explored in depth: (1) Heterogeneous
      single-cell measurements and their integration into tissue and organism models;
      (2) Functional, molecular, and structural imaging of engineered tissue in vitro
      and in vivo; (3) New technologies for characterizing cells and tissues in situ;
      (4) Imaging for targeted cell, gene, and drug delivery.

PMID- 18612828
TI  - Outflow boundary conditions for arterial networks with multiple outlets.
AB  - Simulation of blood flow in three-dimensional geometrically complex arterial
      networks involves many inlets and outlets and requires large-scale parallel
      computing. It should be based on physiologically correct boundary conditions,
      which are accurate, robust, and simple to implement in the parallel framework.
      While a secondary closure problem can be solved to provide approximate outflow
      conditions, it is preferable, when possible, to impose the clinically measured
      flow rates. We have developed a new method to incorporate such measurements at
      multiple outlets, based on a time-dependent resistance boundary condition for the
      pressure in conjunction with a Neumann boundary condition for the velocity.
      Convergence of the numerical solution for the specified outlet flow rates is
      achieved very fast at a computational complexity comparable to the widely used
      Resistance or Windkessel boundary conditions. The method is verified using a
      patient-specific cranial vascular network involving 20 arteries and 10 outlets.

PMID- 18612829
TI  - Herbs and other botanicals in cancer patient care.
AB  - OPINION STATEMENT: Non-prescription herbal remedies are commonly used by cancer
      patients in efforts to control their disease or to manage symptoms associated
      with cancer and cancer treatments. We address the issues surrounding the use of
      herbs, herbal compounds, and other botanical agents in the oncology context.
      Botanicals are biologically active agents that can be useful under appropriate
      circumstances, but they may be counterproductive when used by patients on
      chemotherapy or on other prescription medications. Herbs and other botanical
      agents, despite common public belief, are not benign. They should be understood
      as unrefined pharmaceuticals, with the capacity to produce physiologic change for
      better or worse. Indeed, many prescription drugs, chemotherapeutic agents among
      them, were derived from plants and other natural agents, and the search for
      additional constituents of plants, animals, and minerals for use as
      pharmaceutical agents remains an active effort on many fronts. Cautions,
      appropriate application, and potential utility of botanical agents are discussed
      below, and sources of reliable information are provided.

PMID- 18612830
TI  - Formulation and evaluation of bi-layer tablet of metoclopramide hydrochloride and
      ibuprofen.
AB  - The aim of this study was to prepare bi-layer tablet of Metoclopramide
      Hydrochloride (MTH) and Ibuprofen (IB) for the effective treatment of migraine.
      MTH and IB were formulated as immediate and sustained release layer respectively.
      MTH was formulated as immediate release layer by using various disintegrants like
      Ac-Di-Sol, Polyplasdone XL, Explotab, Agar and Gellan Gum. Treated form of gellan
      gum and agar was prepared and compared for their disintegrant efficiency with
      other disintegrants. IB was formulated as sustained release layer using
      hydrophilic matrix (hydroxypropylmethylcellulose [HPMC K(4)M]). The effect of
      concentration of hydrophilic matrix (HPMC K(4)M), binder (polyvinylpyrollidone
      [PVP K(30)]) and buffer (sodium bicarbonate) on IB release was studied. The
      dissolution study of sustained release layer showed that an increasing amount of
      HPMC or PVP K(30) results in reduced IB release. The inclusion of buffer (sodium
      bicarbonate) enhanced the release of IB from sustained release layer. The
      rational for formulation of bi-layer tablet of these two drugs in combination was
      (1) MTH increases the absorption of acidic non-steroidal anti-inflammatory drug
      (NSAID) by increasing gastric motility. So sequential release of MTH (as
      immediate release) and IB (as sustained release) was suitable for treatment of
      migraine. (2) MTH was degraded when prolonged contact with acidic NSAID. Bi-layer
      tablet was suitable for preventing direct contact of these two drugs and thus to
      maximize the efficacy of combination of two drugs for migraine.

PMID- 18612831
TI  - CONFIRM: connecting fragments found in receptor molecules.
AB  - A novel algorithm for the connecting of fragment molecules is presented and
      validated for a number of test systems. Within the CONFIRM (Connecting Fragments
      Found in Receptor Molecules) approach a pre-prepared library of bridges is
      searched to extract those which match a search criterion derived from known
      experimental or computational binding information about fragment molecules within
      a target binding site. The resulting bridge 'hits' are then connected, in an
      automated fashion, to the fragments and docked into the target receptor. Docking
      poses are assessed in terms of root-mean-squared deviation from the known
      positions of the fragment molecules, as well as docking score should known
      inhibitors be available. The creation of the bridge library, the full details and
      novelty of the CONFIRM algorithm, and the general applicability of this approach
      within the field of fragment-based de novo drug design are discussed.

PMID- 18612832
TI  - Acetylcholinesterase supports anchorage independence in colon cancer.
AB  - Various roles have been attributed to Acetylcholinesterase (AChE) in cancer.
      Evidence exists for a pro-apoptotic function, consistent with a protective role
      of AChE. Because other reports suggested that upregulated AChE in some tumors may
      control cell adhesion, we tested the effects of AChE on anchorage independence
      (an essential component of metastasis) of colon tumor cells. Several AChE
      inhibitors dose-dependently suppressed colony formation of HTB-38 cells in soft
      agar. This effect of AChE was confirmed with HTB-38 cells stably overexpressing
      AChE. In contrast, cell proliferation was not altered by the effective doses of
      these chemical inhibitors or by transfected AChE. Protection from cell cycle
      arrest consecutive to cancer cell detachment may be conveyed by changes in cell
      matrix interactions. Reflective of such changes, the AChE overexpressing cells
      adhered more strongly to Fibronectin than did the vector controls. The AChE
      dependent adhesion was RGD-dependent and accompanied by increased c-Myb DNA
      binding, suggesting that AChE upregulates an Integrin receptor via c-Myb. In
      support of these observations, we find AChE message and protein to be expressed
      in a large fraction of colon cancers and in all colon tumor cell lines analyzed,
      but only rarely in normal colon specimens. Our results imply a dual role for AChE
      in colon cancer. While the anti-apoptotic effects of AChE may be protective
      against early stages of tumorigenesis, this gene product may support the later
      stages of transformation by enhancing anchorage independent growth. The induction
      of Integrins could render the cells independent of microenvironmental cues and
      override cell cycle arrest after deadhesion.

PMID- 18612833
TI  - Statistical models and time series forecasting of sulfur dioxide: a case study
      Tehran.
AB  - This study performed a time-series analysis, frequency distribution and
      prediction of SO(2) levels for five stations (Pardisan, Vila, Azadi, Gholhak and
      Bahman) in Tehran for the period of 2000-2005. Most sites show a quite similar
      characteristic with highest pollution in autumn-winter time and least pollution
      in spring-summer. The frequency distributions show higher peaks at two
      residential sites. The potential for SO(2) problems is high because of high
      emissions and the close geographical proximity of the major industrial and urban
      centers. The ACF and PACF are nonzero for several lags, indicating a mixed (ARMA)
      model, then at Bahman station an ARMA model was used for forecasting SO(2). The
      partial autocorrelations become close to 0 after about 5 lags while the
      autocorrelations remain strong through all the lags shown. The results proved
      that ARMA (2,2) model can provides reliable, satisfactory predictions for time
      series.

PMID- 18612834
TI  - Monitoring of Cd pollution in soils and plants irrigated with untreated sewage
      water in some industrialized cities of Punjab, India.
AB  - The disposal of industrial and sewage water is a problem of increasing importance
      throughout the world. In India, and most of the developing countries untreated
      sewage and industrial wastes are discharged on land or into the running water
      streams which is used for irrigating crops. These wastes often contain high
      amount of trace elements which may accumulate in soils in excessive quantities on
      long term use and enter the food chain through absorption by the plants. Among
      the trace metals, Cd has received the greater attention because of its easy
      absorption and accumulation in plants and animals to levels toxic for their
      health. The objective of this study conducted in three industrially different
      cities viz., Ludhiana, Jalandhar and Malerkotla was to monitor the extent of Cd
      accumulation in soils and plants receiving untreated sewage water. Plant and soil
      samples were collected from sewage and tubewell irrigated areas. Soil samples
      were analysed for texture, pH, EC, organic carbon (OC), CaCO(3), bioavailable
      DTPA-Cd and plant samples were analysed for total Cd. In sewage irrigated soils,
      the mean values of pH were lower but organic carbon and electrical conductivity
      were generally higher both in surface and sub-surface layers of all the three
      cities as compared to tubewell irrigated soils. The mean DTPA- extractable Cd in
      sewage irrigated soil was 6.3- and 4.36-fold in Ludhiana, 3.38- and 1.71-fold in
      Jalandhar and 3.35- and 6.67-fold in Malerkotla in 0-15 and 15-30 cm soil depth,
      respectively, compared with the values in tubewell irrigated soils. The
      accumulation of DTPA-Cd in sewage irrigated soils was restricted to 30 cm depth
      after which the values were generally close to values in tubewell irrigated
      soils. Soil pH, OC, CaCO(3), clay and silt collectively accounted for 37.1%,
      65.1% and 53.9% DTPA-extractable bioavailable Cd in soils of Ludhiana, Jalandhar
      and Malerkotla, respectively. Lower R(2) values in Ludhiana suggest that factors
      other than the ones mentioned may be affecting Cd availability. At all sites
      plants receiving sewage irrigation had elevated levels of Cd as compared to the
      plants receiving tubewell irrigation. The mean Cd content of sewage irrigated
      plants irrespective of the city was 5.96 microg g(-1) dry matter as compared to
      0.98 microg g(-1) dry matter in tubewell irrigated plants. The results suggest
      that the intake of Cd obtained from consumption of crops grown on sewage
      irrigated soils would be much higher than the tolerable limits set by WHO and
      may, therefore, prove potentially toxic leading to various health ailments to
      humans and animals.

PMID- 18612835
TI  - A study on the pathological lesions of oviducts of buffaloes diagnosed at
      postmortem.
AB  - The aims of this study were to study the prevalence of oviduct abnormalities of
      buffaloes, investigate bacteria accompanying hydrosalpinx, pyosalpinx and
      salpingitis. In addition, the study was designed to investigate the correlation
      between bacterial infection of the uterus and oviduct lesions in buffaloes.
      Bacteriological examinations were performed on hydrosalpinx, pyosalpinx and
      salpingitis. Hydrosalpinx was found in 28 (6.9%) cases of which 20 (71.4%) were
      found unilaterally and 8 (28.6%) bilaterally. Pyosalpinx was recorded in 12
      (2.9%). Three cases (0.7%) of oviducts filled with blood were recorded.
      Obstruction of oviducts was recorded in 5 (1.2%). Adhesions between mesosalpinx
      and perisalpingeal tissues were observed in 7 (1.7) cases. One case of double
      oviduct was found in the left side of the tract examined. The most prevalent
      bacteria recovered from hydrosalpinx were Corynebacterium hemolyticum and
      Actinomyces bovis, 42.8% and 28.6%, respectively. No correlation was noticed
      between bacteria isolated from the uterus and hydrosalpinx. The most prevalent
      bacteria recovered from pyosalpinx were Escherichia coli, Archanobacterium
      pyogenes and Staphylococcus aureus, 33.3%, 26.7% and 16.7%, respectively. Higher
      rates of leukocyte infiltration (P < 0.01) were observed in the uterine discharge
      and pyosalpinx than hydrosalpinx. In a conclusion, the current study disclosed
      that oviductal lesions seem to be an important problem in buffalo cows. In
      addition, there is no correlation between bacteria isolated from uterus and
      hydrosalpinx. There is a high correlation between bacteria isolated from uterus
      and pyosalpinx and salpingitis. The occurrence of pyosalpinx and salpingitis is
      mainly due to bacterial infection. Bacterial isolates from pyosalpinx and
      salpingitis might be related to ascending infection from the uterus.

PMID- 18612836
TI  - The role of chicken IL-1beta, IL-6 and TNF-alpha in the occurrence of amyloid
      arthropathy.
AB  - In this study, the roles of IL-1beta, IL-6 and TNF-alpha in amyloid arthropathic
      chickens with variable amounts (severe, moderate and mild) of amyloid
      accumulation were investigated. The presence and the levels of cytokines were
      evaluated in serum and in joint tissues by using ELISA and immunohistochemistry,
      respectively. One hundred brown layer chicks were allocated into four groups and
      intra-articular injections of Freund's adjuvant were used to induce amyloid
      arthropathy in Groups II, III and IV. Vitamin A in group II, and
      methylprednisolone in Group IV were added to enhance and to reduce the severity
      of amyloidosis, respectively. At the end of the study, a positive correlation was
      observed among the incidence and severity of amyloidosis, the serum amyloid A
      levels and the IL-1beta values both in the serum and tissues. Elevation in the
      tissue TNF-alpha levels in parallel with the severity of amyloidosis has also
      been noted. As a conclusion, IL-1beta appears to play an important role in avian
      AA amyloidosis either alone or in combination with TNF-alpha. Further
      investigation is needed for understanding the role of the pro-inflammatory
      cytokines in avian AA amyloidosis.

PMID- 18612838
TI  - Ripening in papaya fruit is altered by ACC oxidase cosuppression.
AB  - Papaya (Carica papaya) is a very important crop in many tropical countries but it
      is highly susceptible to parasitic diseases, physiological disorders, mechanical
      damage and fruit overripening. Here we report a study on ACC oxidase
      cosuppression and its effects on papaya fruit ripening. Papaya ACC oxidase was
      isolated using PCR and embriogenic cells transformed by biolistic using the CaMV
      35S promoter to drive the expression of the PCR fragment in sense orientation.
      Fifty transgenic lines were recovered and 20 of those were grown under field
      conditions. Southern analysis showed incorporation of the transgene in different
      copy numbers in the papaya genome. Fruits were evaluated in terms of texture
      (firmness), colour development, respiration and ethylene production. A sharp
      reduction in ethylene and CO2 production was detected, whereas softening and
      colour development of the peel were also altered. Overall, transgenic fruits
      showed a delay in ripening rate. A reduction in mRNA level for ACC oxidase in
      transgenic fruit was clearly detectable by northern blot. More studies are
      necessary before this technology can be used to extend the shelf life of papaya
      fruit.

PMID- 18612839
TI  - Targeted modulation of sinapine biosynthesis pathway for seed quality improvement
      in Brassica napus.
AB  - Arabidopsis thaliana and other members of the Brassicaceae accumulate the
      hydroxycinnamic acid esters sinapoylmalate in leaves and sinapoylcholine in
      seeds. Our recent understanding of the phenylpropanoid pathway although complex
      has enabled us to perturb the sinapine biosynthesis pathway in plants. Sinapine
      (sinapoylcholine) is the most abundant antinutritional phenolic compound in seeds
      of cruciferous species and therefore is a target for elimination in canola
      (Brassica napus) meal. We analysed A. thaliana mutants with specific blocks in
      the phenylpropanoid pathway and identified mutant lines with significantly
      altered sinapine content. Knowledge gained from A. thaliana was extended to B.
      napus and the corresponding phenylpropanoid pathway genes were manipulated to
      disrupt sinapine biosynthesis in B. napus. Based on our understanding of the A.
      thaliana genetics, we have successfully developed transgenic B. napus lines with
      ferulic acid 5-hydroxylase (FAH) and sinapoylglucose:choline sinapoyltransferase
      (SCT)-antisense. These lines with concomitant downregulation of FAH and SCT
      showed up to 90% reduction in sinapine. In addition to reduced sinapine content,
      we detected higher levels of free choline accumulation in the seeds. These
      results indicate that it is possible to develop plants with low sinapine and
      higher choline by manipulating specific steps in the biosynthetic pathway. These
      improvements are important to add value to canola meal for livestock feed.

PMID- 18612840
TI  - Identifying and genotyping transgene integration loci.
AB  - The random germline integration of genetically engineered transgenes has been a
      powerful technique to study the role of particular genes in variety of biological
      processes. Although the identification of the transgene insertion site is often
      not essential for functional analysis of the transgene, identifying the site can
      have practical benefit. Enabling one to distinguish between animals that are
      homozygous or hemizygous for the transgene locus could facilitate breeding
      strategies to produce animals with a large number of genetic markers.
      Furthermore, founder lines generated with the same transgene construct may
      exhibit different phenotypes and levels of transgene expression depending on the
      site of integration. The goal of this report was to develop a rapid protocol for
      the identification and verification of transgene insertion sites. To identify
      host genomic sequences at the coagulation Factor X transgene integration site,
      DNA from a tail snip of the transgenic mouse was digested with NcoI and
      circularized using T4 DNA ligase. Using appropriately positioned PCR primers
      annealing to a transgene fragment distal to a terminal transgene restriction site
      (NcoI), one could amplify a fragment containing the transgene terminal region and
      extending into the flanking genomic sequence at the insertion site. DNA sequence
      determination of the amplicon permitted identification of the insertion site
      using a BLASTN search. FISH analysis of a metaphase spread of primary fibroblasts
      derived from the transgenic mouse was consistent with the identification of
      insertion site near the end of mouse chromosome 14. Identification of transgene
      insertion sites will facilitate genotyping strategies useful for the construction
      of mice with multiple engineered genetic markers and to distinguish among
      different founder lines generated by the same transgene. Furthermore,
      identification of the insertion site is necessary to analyze unexpected
      phenotypes that might be caused by insertional inactivation of an endogenous
      gene.

PMID- 18612841
TI  - The end of the journal, as we know it: commentary.

PMID- 18612843
TI  - Computational analysis of photosynthetic systems.
AB  - The use of various computational techniques for the study of photosynthetic
      systems is described ranging from genome analysis to density functional
      simulations of the oxygen evolving complex of PSII. The use of simulations for
      analyzing protein structures can aid in clarifying ambiguous and incomplete
      experimental results to identifying underlying rules to create efficient light
      initiated charge separation at high efficiency.

PMID- 18612842
TI  - Bacteriophytochromes in anoxygenic photosynthetic bacteria.
AB  - Since the first discovery of a bacteriophytochrome in Rhodospirillum centenum,
      numerous bacteriophytochromes have been identified and characterized in other
      anoxygenic photosynthetic bacteria. This review is focused on the biochemical and
      biophysical properties of bacteriophytochromes with a special emphasis on their
      roles in the synthesis of the photosynthetic apparatus.

PMID- 18612844
TI  - Imaging of the coronary venous system in patients with congestive heart failure:
      comparison of 16 slice MSCT and retrograde coronary sinus venography: comparative
      imaging of coronary venous system.
AB  - BACKGROUND: Knowledge of the anatomy of the coronary venous system (CVS) is
      important for planning of cardiac interventions like cardiac resynchronization
      therapy or percutaneus mitral annuloplasty. Different methods have been used for
      preprocedural visualization of the CVS. However, limited data is available
      comparing invasive retrograde coronary sinus angiography (CSA) and non-invasive
      multi slice computed tomography (MSCT). Thus, a comparison of retrograde CSA and
      ECG-gated MSCT for the visualization of the CVS in patients with congestive heart
      failure (CHF) was performed. METHODS: 20 patients (male: 11) with CHF underwent
      CSA and MSCT (16 x 0.75 mm collimation, tube voltage: 120 kV, tube current: 550
      mAs(eff)). Both methods were compared with respect to vessel diameter and
      visibility. RESULTS: Vessel visualization was better using retrograde CSA except
      for middle cardiac vein and small veins which were better seen with MSCT.
      Overall, there was a trend that MSCT detected more vessels. Vessel diameters were
      larger measured using retrograde CSA, but only statistically significant for the
      coronary sinus and middle cardiac vein. CONCLUSION: Whereas MSCT is more suitable
      for an overview, retrograde CSA offers a more detailed visualization of the CVS
      including marginal and posterior veins than MSCT. Thus, retrograde CSA allows a
      better display of target vessels commonly used for cardiac interventions.
      Overall, these two imaging techniques offer complementary information.

PMID- 18612845
TI  - Activation of ERK-FAK signaling pathway and enhancement of cell migration
      involved in the early interaction between oral keratinocytes and Candida
      albicans.
AB  - PURPOSES: To investigate the early molecular events in oral keratinocytes induced
      by Candida albicans challenge. METHODS: The oral keratinocyte cell line, Tca8113,
      was used to study the molecular events induced by C. albicans challenge in oral
      keratinocytes. The phosphorylation statuses of extracellular signal-regulated
      protein kinase (ERK) and focal adhesion kinase (FAK) upon C. albicans challenge
      were assessed using specific antibodies and western blotting. Specific inhibitors
      for ERK and FAK were used to validate the involvement of ERK-FAK signaling
      cascade. A Transwell insert system-based migration study was performed to
      evaluate the involvement of the C. albicans-dependent ERK-FAK activation with
      cell migration. RESULTS: Following the stimulation with C. albicans, a transient
      activation of ERK was observed, which reached a peak at 10 min post stimulation.
      Similarly, a transient activation of FAK, the downstream substrate of ERK, was
      also observed upon C. albicans challenges, which reach the maximum at 20 min.
      Specific inhibitors for ERK and FAK abolished the C. albicans-induced ERK and FAK
      activations. The elevated migratory ability of oral keratinocyte was observed
      upon stimulation with C. albicans, and was synchronous with the ERK-FAK
      activation. CONCLUSION: ERK-FAK signaling cascades are involved in the early
      interaction between the oral keratinocytes and C. albicans, which appears to be
      linked with the enhanced cell migration.

PMID- 18612846
TI  - Quantification of silkworm coactivator of MBF1 mRNA by SYBR Green I real-time RT
      PCR reveals tissue- and stage-specific transcription levels.
AB  - Transcriptional coactivators play a crucial role in gene transcription and
      expression. Multiprotein bridging factor 1 (MBF1) is a transcriptional
      coactivator necessary for transcriptional activation caused by DNA-binding
      activators, such as FTZ-F1 and GCN4. Until now, very few studies have been
      reported in the silkworm. We selected the Bombyx mori because it is a model
      insect and acts as an economic animal for silk industry. In this study, we
      conducted the quantitative analysis of MBF1 mRNA in silkworm B. mori L. with
      actin (A3) as internal standard by means of SYBR Green I real-time RT-PCR method.
      The total RNA was extracted from the silk gland, epidermis, fat body, and midguts
      of the fifth instar B. mori larvae. The mRNA was reverse transcripted, and the
      cDNA fragments of MBF1 mRNA and actin gene were amplified by RT-PCR using
      specific primers. MBF1 mRNA expression in different tissues of silkworm B. mori
      L. was quantified using standardized SYBR Green I RT-PCR. The results suggested
      MBF1 gene was expressed in all investigated organs but highly expressed in the
      silk gland, showing its relation to biosynthesis of silk proteins.

PMID- 18612847
TI  - Quality control of cultured tissues requires tools for quantitative analyses of
      heterogeneous features developed in manufacturing process.
AB  - Tissue engineering and related technology have attracted a great deal of medical
      attention as promising fields for curing defective tissues in vivo. Nowadays,
      many companies have been established for supplying the reconstructed grafts of
      cultured tissues for transplantation. The manufacturing processes generally deals
      with the handlings of starter cells offered by patients (or donors) as raw
      materials to cultured tissues as products, requiring the construction of novel ex
      vivo methodologies based on principles different from conventional processes for
      chemical and pharmaceutical productions. In addition, the raw materials have
      heterogeneity depending on the state of patients and location of cell harvests,
      and the products possess spatial cell distribution in the three dimensional
      structure. These features request a unique strategy in manufacturing process
      accompanied with the quality control for raw materials and products. This review
      article describes the contribution of tissue bankers and biochemical engineers to
      the quality control of cultured tissues during manufacturing, introducing the
      advances in methodologies to evaluate spatial heterogeneity of cells (or
      aggregates) and matrices in cultured tissues.

PMID- 18612848
TI  - The impact of the International Atomic Energy Agency (IAEA) program on radiation
      and tissue banking in Mexico.
AB  - Tissue banking started in Mexico in 1948-1949, when two bone banks were
      established, one at the Infantile Hospital of Mexico and other at the Central
      Military Hospital. Mexico has benefited for the implementation of the IAEA
      program since through it has been able to settle down and to consolidate the
      Tissue Bank at the Instituto Nacional de Investigaciones Nucleares ININ (National
      Institute for Nuclear Research). This is the only bank in Latin America that has
      a Quality Management System in force, certified under ISO 9001:2000 since August
      1, 2003. The first tissue processed was amnion. The main products of the BTR are
      amnion and pig skin. Both are biological tissues which their main use is as a
      wound dressing in patients with burns, scars, diabetic ulcers, epidermolysis
      bullosa, damaged ocular surface, etc. The General Health Law, published in 1984
      and reformed in June 19, 2007, describes the procedure for the disposal of
      organs, tissues and human cadavers in its fourteenth title and in the Regulation
      for Sanitary Control. During the period 2001-2005, the ININ Tissue Bank produced
      292 sterilised tissues (amnion, 86,668 cm(2), and frozen pig skin, 164,220 cm(2),
      at an estimated cost of 1,012,668 Mexican pesos. Until 2006, one hundred eighty
      five (185) patients have been treated with the use of sterilised tissues produced
      by the ININ Tissue Bank. The radiation source used for sterilisation of tissues
      is an industrial Cobalt-60 irradiator model JS-6500 AECL, which belongs to ININ.
      This equipment is located in other building, close to the BTR, in the Centro
      Nuclear de Mexico "Dr. Nabor Carrillo Flores" (Nuclear Center of Mexico). Until
      2006, six hospitals use in a routine way the sterilised tissues produced by the
      ININ Tissue Bank, for the treatment of burns originated by diverse agents like
      flame, electricity, liquids in boil, chemical reagents, as well as for the
      reconstruction of the ocular surface. Two of these hospitals treat patients of
      very low economic incomes, mainly needy individuals, who cannot afford to pay
      this type of treatments in other hospitals due to their high cost. The results
      obtained up to now are highly promising.

PMID- 18612849
TI  - The impact of the International Atomic Energy Agency (IAEA) program on radiation
      and tissue banking in Peru.
AB  - The tissue bank "Rosa Guerzoni Chambergo" (RGCTB) located at the Child's Health
      Institute was inaugurated in 1996, with the financial and technical support of
      the IAEA program on radiation and tissue banking. Since 1998, the biological
      bandage of fresh and lyophilised pigskin, amnion and bone tissue is processed
      routinely in this bank. In all cases, the tissue is sterilised with the use of
      Cobalt-60 radiation, process carried out at the Laboratories of Irradiation of
      the Peruvian Institute of Nuclear Energy (IPEN). The tissue bank in the Child's
      Health Institute helped to save lives in an accident occurred in Lima, when a New
      Year's fireworks celebration ran out of control in January 2002. Nearly 300
      people died in the tragic blaze and hundreds more were seriously burned and
      injured. Eight Lima hospitals and clinics suddenly were faced with saving the
      lives of severely burned men, women and children. Fortunately, authorities were
      ready to respond to the emergency. More than 1,600 dressings were sterilised and
      supplied to Lima surgeons. The efforts helped save the lives of patients who
      otherwise might not have survived the Lima fire. Between 1998 and September 2007,
      35,012 tissue grafts were produced and irradiated. Radiation sterilised tissues
      are used by 20 national medical institutions as well as 17 private health
      institutions. The tissue bank established in Peru with the support of the IAEA is
      now producing the following tissues: pigskin dressings, fresh and freeze-dried;
      bone allografts, chips, wedges and powdered, and amnion dressings air-dried. It
      is also now leading the elaboration of national standards, assignment being
      entrusted by ONDT (Organizacion Nacional de Donacion y Transplantes; National
      Organisation on Donation and Transplant). This among other will permit the
      accreditation of the tissue bank. In this task is also participating IPEN.

PMID- 18612850
TI  - Electronic tracking of human brain samples for research.
AB  - Insight into the pathogenesis of neurodegenerative disorders requires accurately
      categorized postmortem human brain tissue. This article introduces electronic
      tissue tracking and management as implemented at New York Brain Bank (NYBB)
      through processing of the brain at fresh state and storing standardized frozen
      samples. NYBB tissue tracking uses a relational database to co-register a bar
      coded, unique sample identifier to unique coordinates in the three-dimensional
      freezer space, allowing immediate retrieval of stored samples without further
      dissection. In the 5 years since the inception of NYBB (2002-2007) 560 brains
      (63,252 fresh frozen samples) were processed and as of 11/2007, 54,242 samples
      are stored seven freezers occupying 81% of maximum capacity of NYBB. Within the
      same time period, 1,094 requests were processed and 9,096 samples were disbursed
      with an average turnaround time of five working days. The NYBB system of brain
      banking has the following key advantages: (1) The dissection of the brain and the
      harvest of samples at the fresh state improve their anatomic specificity and
      quality; (2) samples are ready for immediate disbursement once categorized
      diagnostically, reducing the time between the receipt of request and disbursement
      of samples; (3) the methods prevent thaw-refreeze cycles and carving out of
      regions of interest from frozen tissue, which is cumbersome and deleterious to
      the both samples and source brains; (4) accurate quantitative data on stored
      samples according to anatomical regions and distributive diagnosis guides future
      sample collection and fosters effective use of limited resources.

PMID- 18612852
TI  - The SP-AP compound wave in patients with auditory neuropathy.
AB  - CONCLUSIONS: This study suggests that the asynchronization of the cochlear
      afferent pathway may be one mechanism of the etiopathogenesis of auditory
      neuropathy. OBJECTIVE: To investigate the characteristics of the SP-AP compound
      wave and its generating mechanism in patients with auditory neuropathy. SUBJECTS
      AND METHODS: The electrocochleogram (ECochG) was recorded with external ear canal
      electrode in patients with auditory neuropathy and normal subjects. The peak
      latency, amplitude, and time course of the SP-AP compound wave were measured by
      using an 'assessor-blind' study. The discrepancy between the two groups was
      evaluated by statistical analysis. RESULTS: The SP-AP compound waveform in the
      auditory neuropathy patient group was unrepresentative. The transient character
      of the SP-AP compound wave was more atypical than that for the normal cases. SP
      dominance (-SP/AP>0.4) appeared. The amplitude of both AP and SP was lower than
      that of the control group. The width of the SP-AP compound wave at one-third of
      its peak was greater than that of the control group.

PMID- 18612853
TI  - Cancer of the oro- and hypopharynx - when to expect recurrences?
AB  - CONCLUSION: Relapse-free survival (RFS) of patients suffering from cancers
      located in the oro- and hypopharynx (COH) is strongly related to the localization
      and initial tumor stage; 25% of relapses remain undetected by the patients
      themselves. To detect relapse at an early stage oncologic follow-up should be
      performed at close intervals during the first 3 years. For confirmation imaging
      procedures should be indicated generously as well as control endoscopy under
      general anesthesia. OBJECTIVES: COH are often characterized by a rapid
      progression of disease in case of relapse. Most of these relapses are already
      incurable at the time of diagnosis. The aim of the present study was the
      assessment of time intervals between initial diagnosis of the primary tumor and
      its relapse. PATIENTS AND METHODS: The course of disease of 280 patients was
      analyzed. RFS was evaluated statistically. RESULTS: RFS was strongly related to
      the location of the primary tumor. The median RFS of patients suffering from
      oropharyngeal cancer was longer (86 months) than that of patients with
      hypopharyngeal carcinomas (45 months). Patients with COH revealed an accumulation
      of recurrent disease within the first 33 months after initial diagnosis. Within
      the first 2 years more than 60% of COH recurred. After 3 years 80% had developed
      a relapse.

PMID- 18612854
TI  - Approach/avoidance motives, test emotions, and emotional regulation related to
      testing.
AB  - This research stems from our program of work that focuses on understanding how
      students regulated their emotions related to testing. The primary goal for this
      study was to incorporate the approach/ avoidance motives into a model of
      emotional regulation related to testing. In addition, a secondary goal was to
      report on efforts at construct validation of the scores obtained during the
      refinement of the Emotional Regulation Related to Testing (ERT) Scale. Our
      results suggest that underlying beliefs, such as approach/avoid motives and the
      cognitive-appraisal process, of the ERT had both direct and indirect effects to
      both pleasant and unpleasant emotions related to testing. In addition, the ERT
      accounted for 56% of the variance in Pleasant and 87% of Unpleasant Test
      Emotions.

PMID- 18612851
TI  - The pursuit of ES cell lines of domesticated ungulates.
AB  - In contrast to differentiated cells, embryonic stem cells (ESC) maintain an
      undifferentiated state, have the ability to self-renew, and exhibit pluripotency,
      i.e., they can give rise to most if not all somatic cell types and to the germ
      cells, egg and sperm. These characteristics make ES cell lines important
      resources for the advancement of human regenerative medicine, and, if established
      for domesticated ungulates, would help make possible the improvement of farm
      animals through their contribution to genetic engineering technology. Combining
      other genetic engineering technologies, such as somatic cell nuclear transfer
      with ESC technology may result in synergistic gains in the ability to precisely
      make and study genetic alterations in mammals. Unfortunately, despite significant
      advances in our understanding of human and mouse ESC, the derivation of ES cell
      lines from ungulate species has been unsuccessful. This may result from a lack of
      understanding of species-specific mechanisms that promote or influence cell
      pluripotency. Thorough molecular characterizations, including the elucidation of
      stem cell "marker" signaling cascade hierarchy, species-appropriate pluripotency
      markers, and pluripotency-associated chromatin alterations in the genomes of
      ungulate species, should improve the chances of developing efficient,
      reproducible technologies for the establishment of ES cell lines of economically
      important species like the pig, cow, goat, sheep and horse.

PMID- 18612855
TI  - Think aloud: acute stress and coping strategies during golf performances.
AB  - A limitation of the sport psychology coping literature is the amount of time
      between a stressful episode and the recall of the coping strategies used in the
      stressful event (Nicholls & Polman, 2007). The purpose of this study was to
      develop and implement a technique to measure acute stress and coping during
      performance. Five high-performance adolescent golfers took part in Level 2
      verbalization think aloud trials (Ericsson & Simon, 1993), which involved
      participants verbalizing their thoughts, over six holes of golf. Verbal reports
      were audio-recorded during each performance, transcribed verbatim, and analyzed
      using protocol analysis (Ericsson & Simon, 1993). Stressors and coping strategies
      varied throughout the six holes, which support the proposition that stress and
      coping is a dynamic process that changes across phases of the same performance
      (Lazarus, 1999). The results also revealed information regarding the sequential
      patterning of stress and coping, suggesting that the golfers experienced up to
      five stressors before reporting a coping strategy. Think aloud appears a suitable
      method to collect concurrent stress and coping data.

PMID- 18612856
TI  - How job demands, resources, and burnout predict objective performance: a
      constructive replication.
AB  - The present study uses the Job Demands-Resources model (Bakker & Demerouti, 2007)
      to examine how job characteristics and burnout (exhaustion and cynicism)
      contribute to explaining variance in objective team performance. A central
      assumption in the model is that working characteristics evoke two psychologically
      different processes. In the first process, job demands lead to constant
      psychological overtaxing and in the long run to exhaustion. In the second
      process, a lack of job resources precludes actual goal accomplishment, leading to
      cynicism. In the present study these two processes were used to predict objective
      team performance. A total of 176 employees from a temporary employment agency
      completed questionnaires on job characteristics and burnout. These self-reports
      were linked to information from the company's management information system about
      teams' (N=71) objective sales performance (actual sales divided by the stated
      objectives) during the 3 months after the questionnaire data collection period.
      The results of structural equation modeling analyses did not support the
      hypothesis that exhaustion mediates the relationship between job demands and
      performance, but confirmed that cynicism mediates the relationship between job
      resources and performance suggesting that work conditions influence performance
      particularly through the attitudinal component of burnout.

PMID- 18612857
TI  - Role of a 'stay well' approach in the management of bipolar disorder.

PMID- 18612858
TI  - Pro re nata medication for psychiatric inpatients: time to act.
AB  - Pro re nata (PRN; 'as needed') medication is an archetypal mainstay for managing
      acute psychiatric inpatient symptoms and behaviours. Psychiatric and mental
      health nursing practices have circumnavigated the development of a uniform
      medical-ethical standard for the administration of PRN psychotropic medication.
      This paper examines the evidence for administration of PRN psychotropic
      medications and, in the context of evidence-based best practice, current mental
      health policy and professional ethics, proposes a standardized Australian PRN
      administration protocol. The procedures and circumstances leading to a nurse
      administering psychotropic PRN medication are divided into five simple steps,
      namely (i) medical prescription; (ii) nurse evaluation of patient indications for
      an intervention; (iii) nurse consideration of therapeutic options; (iv) obtaining
      patient informed consent; and (v) documentation of outcomes of PRN
      administration. The literature associated with each step is reviewed, along with
      national and international professional ethics, guidelines and patient rights
      documents pertaining to the care of mental health patients. Recommendations for
      best-practise care are discussed for each step. There is a lacuna of published
      evidence supporting the use of PRN medications in psychiatric inpatients. Yet
      there is published evidence that PRN medications are associated with increased
      risks of morbidity, inappropriate use, may result in above-recommended dosages or
      polypharmacy, and complicate the assessment of efficacy of regular scheduled
      medicines. Alternative non-pharmacological treatment options to PRN medication
      are effective and associated with fewer side-effects. There are no national
      explicit standards, operational criteria or quality assurance for the use of PRN
      medication in inpatient psychiatric units. Contemporary PRN practices are largely
      unregulated and driven by essentially anecdotal evidence, leaving the clinicians
      and the service open to claims of poor accountability and misuse (intentional and
      unintentional) of psychotropic medications. Development of best practice
      guidelines for the use of PRN administration is essential.

PMID- 18612859
TI  - Echopraxia in schizophrenia: possible mechanisms.
AB  - The aim of the current study was to present a possible mechanism underpinning
      echopraxia in schizophrenia. It is proposed that echopraxia occurs in
      schizophrenia when the mirror neuron system provides a representation to the
      inferior frontal gyrus (IFG) and the motor cortex (and via the IFG, to the
      anterior cingulate cortex) and that this potential becomes executed movement,
      when the disorder is associated with decreased inhibition and increased arousal.

PMID- 18612860
TI  - Attitudes of staff towards patients with personality disorder in community mental
      health teams.
AB  - OBJECTIVE: The purpose of the present paper was to assess the attitudes of
      clinicians working with personality disordered patients. METHODS: Secondary
      analysis of the Comorbidity of Substance Misuse and Mental Illness Collaborative
      (COSMIC) data set was undertaken using a priori hypothesis testing. The null
      hypothesis was that there would be no measurable difference between the attitudes
      of mental health professionals toward patients with a clinical diagnosis of
      personality disorder and those with an instrument-rated diagnosis of personality
      disorder. The potential confounders of global psychopathology, need, social
      functioning and documented aggression were assessed as possible reasons
      explaining a rejection of the null hypothesis. RESULTS: Clinicians believed those
      with the clinical diagnostic label of personality disorder to be more difficult
      to manage than personality-disordered patients identified by a research tool who
      did not carry this label. These attitudes were not explained by the potential
      confounders of psychopathology, social morbidity or acts of aggression.
      CONCLUSIONS: An awareness of a personality disorder diagnosis is associated with
      a clinician belief that patients will be harder to manage. Objective measures of
      potential confounders do not explain why this group should be harder to manage.
      One explanation of this finding is that the label 'personality disorder' is
      stigmatizing. This may also explain the disparity between clinical and research
      assessments of personality disorder.

PMID- 18612861
TI  - Professional attitudes towards deliberate self-harm in patients with borderline
      personality disorder.
AB  - OBJECTIVE: The aim of the present study was to assess the attitudes of mental
      health and emergency medicine clinicians towards patients diagnosed with
      borderline personality disorder. The clinician gender, primary occupation and
      service setting, level of university training and years of experience, frequency
      of clinical contact, and completion of specific training in borderline
      personality disorder were expected to influence the attitudes of health
      professionals towards working with borderline patients that engage in self-harm.
      METHOD: A purpose-designed questionnaire and an assessment tool to quantify
      attitudinal levels were used to collect demographic information and assess the
      attitudes of 140 mental health and emergency medicine practitioners across two
      Australian health services and a New Zealand health service. RESULTS:
      Statistically and clinically significant differences were found between emergency
      medical staff and mental health clinicians in their attitudes towards working
      with borderline personality disorder. The strongest predictor of attitudes was
      whether the clinician worked in emergency medicine or mental health. This was
      followed by years of experience and specific training in personality disorders as
      significant predictors of attitudes to self-harm. CONCLUSIONS: The implications
      of these findings for the professional training of clinicians in the management
      and treatment of borderline personality disorder patients are discussed.

PMID- 18612862
TI  - Shyness 1: distance treatment of social phobia over the Internet.
AB  - OBJECTIVE: The purpose of the present study was to examine the effectiveness of
      an Internet-based clinician-assisted computerized cognitive behavioural therapy
      programme for social phobia. METHOD: A total of 105 individuals with social
      phobia were randomly assigned to a six-lesson cognitive behavioural treatment
      programme or to a waitlist control group. Treatment consisted of four components:
      six online lessons; homework assignments; participation in an online discussion
      forum; and regular email contact with a therapist. An intention-to-treat model
      was used for data analyses. RESULTS: A total of 78% of treatment group
      participants completed all lessons, and post-treatment data were obtained from
      93/105 participants. Significant post-treatment differences between treatment and
      waitlist participants were found on two measures of symptoms of social phobia.
      Mean within- and between-group effect sizes (Cohen's d) for the primary social
      phobia outcome measures were 1.15, and 0.95, respectively. CONCLUSIONS: These
      results were comparable with those obtained in exemplary face-to-face treatment
      programmes. They provide further positive data about the utility of Internet
      based guided self-help programmes for people with common mental disorders.

PMID- 18612863
TI  - Shyness 2: treating social phobia online: replication and extension.
AB  - OBJECTIVE: In a randomized controlled trial Titov et al. (2008) demonstrated
      significant benefit from an Internet- and email-based treatment programme for
      social phobia. The present study (Shyness 2) seeks to replicate that finding and
      compares results with benchmark data. METHOD: Eighty-eight individuals with
      social phobia were randomly assigned to a clinician-assisted computerized
      cognitive behavioural treatment programme or to a waitlist control group.
      Participants completed the same treatment programme used in Shyness 1, consisting
      of six online lessons, cognitive behavioural homework assignments, email contact
      with a therapist, and participation in an online discussion forum. An intention
      to-treat model was used for data analyses. RESULTS: A total of 80% of treatment
      group participants completed all lessons, and post-treatment data were obtained
      from 78/81 participants. Treatment group participants each had an average of 127
      min of therapist contact over the 10 week programme, including an average of 22
      email contacts plus therapist responses to forum postings. Pre- to post-treatment
      differences were seen between treatment and waitlist participants across two
      measures of symptoms of social phobia, and across a measure of disability. Mean
      within- and between-group effect sizes (Cohen's d) across the two primary outcome
      measures were 1.18, and 1.20, respectively. Quantitative and qualitative data
      indicate that the procedure is very acceptable to participants. CONCLUSIONS:
      These results closely replicate those obtained in Shyness 1, indicating that the
      treatment procedure is reliable. These results compare favourably with outcomes
      reported in benchmarking studies from high-quality face-to-face treatment
      programmes for social phobia. These results provide further positive data about
      the utility of Internet-based guided self-help programmes for people with social
      phobia.

PMID- 18612864
TI  - Depression prevalence: is it really increasing?
AB  - OBJECTIVE: There is conflicting evidence as to whether depression prevalence is
      increasing or is stable. Although birth cohort analysis studies show increasing
      prevalence, longitudinal studies do not. To date there are no published
      Australian studies providing long-term estimates of depression prevalence. The
      aim of the present study was to examine the increasing depression prevalence
      hypothesis in an Australian context. METHOD: Data from the 1998 and 2004 South
      Australian Health Omnibus Surveys were re-analysed. In each survey there were
      >3000 participants who were interviewed. The data were weighted to achieve
      representativeness prior to analysis. Depression status was classified by the
      Primary Care Evaluation of Mental Disorders scale (the PRIME-MD) into major,
      other and no depressions. Both univariate and multivariable analyses were used to
      examine depression trends over time and to adjust the data for significant
      background variables. RESULTS: There was no significant increase in the cases of
      patients classified with major depression between 1998 and 2004; there was,
      however, a significant decrease in other depression. The overall unadjusted
      prevalence of major depression was 7.4% (6.8% in 1998 and 8.0% in 2004) and for
      other depression it was 9.5% (10.6% in 1998 and 8.4% in 2004). The highest levels
      of depression, both major and other, were observed among females aged 15-29
      years, and the lowest levels among those aged > or =50 years. The strongest
      predictor of depression was poor overall health status. CONCLUSION: It is time
      for the conventional wisdom that depression is increasing to be reconsidered, and
      for a more realistic perspective, developed from evidence-based analyses, to be
      accepted.

PMID- 18612865
TI  - Familial psychopathology in the First Episode Psychosis Outcome Study.
AB  - OBJECTIVE: The aim of the present study was to characterize the utility of family
      history data for predicting psychiatric and functional status in first-episode
      psychosis (FEP) during the pre-treatment phase of illness, at first presentation,
      and at 18 months follow up. METHOD: An epidemiological study based upon a
      consecutive file audit of 661 patients admitted to the Early Psychosis Prevention
      and Intervention Centre between January 1998 and December 2000 using a
      standardized questionnaire. RESULTS: In the total sample of FEP patients family
      history was not significantly associated with psychiatric or functional status
      pre-treatment, at first presentation, or at 18 months. Male patients with a
      family history of psychotic illness had a longer duration of prodrome compared to
      those with no family history of psychiatric illness (mean=481.4 days, SD=678.0 vs
      mean=383.5 days, SD=524.7; p=0.03). Family history of non-psychotic illness was
      associated with comorbidity at first presentation in female patients, both for
      substance-use related comorbidity (p=0.02) and non-substance-use related
      comorbidity (p=0.03). There was substantial agreement between clinician reports
      of family history of psychosis and those obtained using a structured interview
      instrument (kappa=0.69, 95% confidence interval (CI)=0.41-0.86), but agreement
      for non-psychotic family history was comparatively low (kappa=0.28, 95%CI:=-0.03
      to 0.52). CONCLUSIONS: There are gender differences in the association between
      substance use disorder, duration of prodrome and family history. This supports
      the hypothesis that psychotic illness manifests differently in men and women. In
      the present sample, reports of family history of non-psychotic illness had lower
      convergent validity than reports of psychotic illness. The present reported
      associations with non-psychotic family history should therefore be interpreted
      with caution. Information on gender and family history of psychiatric illness may
      assist clinical diagnosis and determination of treatment in FEP patients,
      especially if specific familial risk factors can be identified.

PMID- 18612866
TI  - Comprehensive description of adolescents admitted to a public psychiatric
      inpatient unit and their families.
AB  - OBJECTIVE: Adolescents accessing inpatient psychiatric services typically have
      severe and complex disturbance. The aim of the present study was to provide a
      comprehensive description of an adolescent inpatient sample by examining their
      psychiatric diagnosis, symptomatology and functioning and associated parental
      mental health, family functioning and cultural and socioeconomic factors. Few
      studies have described all these factors and existing studies have reported
      varying results. METHODS: Participants were 88 adolescents (37 male) aged 12-18
      years (mean=15.4 years) consecutively recruited through a small number of case
      clinicians from a regional metropolitan public inpatient unit over a 5 year
      period. Adolescents and parents participated in clinical interviews and completed
      psychometric measures. Case clinicians provided diagnostic information. RESULTS:
      In contrast to previous studies, adolescents were from a cross-section of
      socioeconomic backgrounds. Results showed a high rate of comorbid Axis I
      diagnoses with depressive disorders the most common principal diagnosis. Two
      thirds of adolescents experienced clinical levels of internalizing problems.
      Clinical levels of thought disturbance and externalizing problems were reported
      for most adolescents, although adolescents self-reported fewer of these symptoms.
      Educational and social difficulties were common. A salient result was the high
      level of family dysfunction reported by multiple informants. Most parents
      reported minimal personality or psychological disturbance but results
      contradicted other studies and may reflect response bias. In a preliminary
      finding, non-English-speaking background and low socioeconomic status were
      associated with a psychosis-related principal diagnosis. CONCLUSION: Findings
      indicate the multiplicity of issues facing adolescent inpatients including
      psychiatric symptoms, impaired personal and family functioning and family
      cultural and background factors. Treatment that focuses on only some of these
      factors may have limited effectiveness.

PMID- 18612867
TI  - Factor structure of the Greek translation of the Scale for the Assessment of
      Thought, Language and Communication.
AB  - OBJECTIVE: The Scale for the Assessment of Thought, Language and Communication
      (TLC) is a widely used instrument for the assessment of formal thought disorder.
      TLC disorders were initially conceptualized as having only two underlying
      dimensions, a negative and a positive one. But studies of the factorial structure
      of the TLC have not provided confirmation for the positive-versus-negative
      distinction. The aim of the present study was to assess the factorial structure
      of the Greek translation of the TLC. METHOD: Subjects were 103 patients (69 male,
      34 female) with psychotic disorders randomly recruited from both inpatient and
      outpatient facilities. The TLC was assessed by two raters based on a 20 min
      clinical interview. RESULTS: Principal component analysis with varimax rotation
      yielded a three-factor structure; the three factors consisted off items
      reflecting (i) disorganization of speech; (ii) peculiarities of speech; and (iii)
      verbosity. The disorganization factor could be further divided into two
      dimensions reflecting disturbances in the flow of ideas and in the structure of
      speech. CONCLUSION: The investigation of the factorial structure of the Greek
      translation of the TLC scale found no support for the positive-versus-negative
      distinction of TLC disorders. Three factors (disorganization, speech
      peculiarities, and verbal productivity) were found to underlie the variance of
      the scale.

PMID- 18612868
TI  - Alert: inaccurate lithium assay results.
AB  - OBJECTIVES: A patient who had experienced bipolar disorder for over 20 years and
      who had been euthymic for most of that period while highly compliant with
      lithium, had falsely low lithium levels reported over two periods, 6 years apart,
      and was actually lithium toxic on the most recent occasion. At that latter time
      the spuriously low lithium levels reported on the assay risked dispelling any
      clinical suspicion of lithium toxicity, although toxicity was later confirmed.
      METHOD: Case report. RESULTS: The latter incident identified a serious problem,
      whereby it is likely that the particular assay risks generating spuriously low
      values when high serum levels of lithium are present--a so-called 'hook
      phenomenon' that has been described for some quantitative immunoassays.
      CONCLUSIONS: It is in situations of high potential gravity--when lithium toxicity
      is present--that lithium quantification is most likely to be compromised and low
      values generated. Also of grave concern is the fact that there are no regulatory
      processes in place to communicate this problem to lithium prescribers.

PMID- 18612869
TI  - Hypersensitive neurological response to lithium in a patient with organic bipolar
      disorder secondary to idiopathic basal ganglia calcification.

PMID- 18612871
TI  - A novel in vivo mouse model for mechanically stimulated bone adaptation--a
      combined experimental and computational validation study.
AB  - To facilitate the investigation of bone formation, in vivo, in response to
      mechanical loading a caudal vertebra axial compression device (CVAD) has been
      developed to deliver precise mechanical loads to the fifth caudal vertebra (C5)
      of the C57BL/6 female mouse. A combined experimental and computational approach
      was used to quantify the micro-mechanical strain induced in trabecular and
      cortical components following static and dynamic loading using the CVAD. Cortical
      bone strains were recorded using micro-strain gages. Finite element (FE) models
      based on micro-computed tomography were constructed for all C5 vertebrae. Both
      theoretical and experimental cortical strains correlated extremely well (R2 >
      0.96) for a Young's modulus of 14.8 GPa, thus validating the FE model. In this
      study, we have successfully applied mechanical loads to the C5 murine vertebrae,
      demonstrating the potential of this model to be used for in vivo loading studies
      aimed at stimulating both trabecular and cortical bone adaptation.

PMID- 18612872
TI  - Prevalence of overweight and obesity among 11-year-old children in Cyprus, 1997
      2003.
AB  - OBJECTIVES: To report 5-year changes in the prevalence of overweight and obesity
      in 11-year-old children in Cyprus. METHODS: This was a school-based study
      performed in Cyprus. A total of 14,090 11-year-old children (males: 51.2%), who
      had been examined in the 1997-8 and 2002-3 school years, were included in the
      study. The International Obesity Task Force (IOTF) cut-offs were used to define
      overweight and obese subjects, and logistic regression models were used to
      estimate 5-year trends. RESULTS: The overall prevalence of overweight children
      was slightly higher in the second period but this change was not statistically
      significant. There was only a significant increase in overweight boys in rural
      areas; odds ratio (OR) (95% confidence interval [CI]) for the 5-year period was
      1.33 (1.10, 1.62; p = 0.004). The overall relative increase in obesity was 17.9%
      and the OR (95% CI) was 1.22 (1.07, 1.38; p = 0.003). Although the prevalence of
      obesity was higher in males in both periods, the relative increase was
      substantially higher in females, 29.6% vs. 11.4%. The relative increase was also
      higher in rural (35.9%) compared with urban areas (8.7%); ORs (95% CI) 1.46
      (1.17, 1.81) vs. 1.10 (0.94, 1.29), respectively. CONCLUSIONS: This is the first
      report documenting increasing rates of obesity among school-aged children in
      Cyprus. Females and children living in rural areas experienced the most striking
      increases. The prevalence of overweight increased only in males living in rural
      areas.

PMID- 18612873
TI  - The episodic buffer and learning in early Alzheimer's disease.
AB  - The role of working memory, specifically the episodic buffer, in the learning
      performance of patients with very mild (n = 18) and mild (n = 12) Alzheimer's
      disease as compared with healthy older adults (n = 29) was investigated using a
      series of word-lists that were manipulated (clustered, unclustered) to explore
      the impact of strategic organizational skills under varying attention conditions
      (full, divided). Results indicated that the learning performance for all three
      groups under full attention was better than that under divided attention, but
      only for the clustered word-lists. Moreover, in contrast to the mild Alzheimer's
      disease group, both the healthy older controls and the very mild Alzheimer's
      disease group demonstrated better performance on clustered word-lists than on
      unclustered lists, suggesting active strategic organizational skills, even at
      delayed free recall. The overall pattern of results indicates a staging of
      working-memory impairment in early Alzheimer's disease.

PMID- 18612874
TI  - A comparison of adjusted spaced retrieval versus a uniform expanded retrieval
      schedule for learning a name-face association in older adults with probable
      Alzheimer's disease.
AB  - We compared the efficacy of two memory training schedules, adjusted spaced
      retrieval and uniform expanded retrieval, for learning a name-face association in
      12 older adults with probable Alzheimer's disease (AD). Nine training sessions
      were administered on alternate days for three weeks. Results yielded a positive
      effect of adjusted spaced retrieval on the proportion of correct recall trials
      and greater success in transferring the learned information to the live target,
      compared to the uniform expanded retrieval schedule. These data suggest that the
      spacing effect may underlie the memorial benefit of spaced retrieval.
      Implications for practical uses of spaced retrieval are considered.

PMID- 18612875
TI  - Dyslexia and rapid visual processing: a commentary.
AB  - It has been suggested that dyslexia is the result of a deficit in rapid sensory
      processing. Several methods have been used to assess this with regards to vision:
      temporal contrast sensitivity, visual persistence, temporal order judgments,
      temporal acuity, and coherent motion. Here we examine these methods. We find that
      several of them--visual persistence, temporal order judgments, and coherent
      motion--are poorly suited to evaluating the dynamic aspects of vision. In the
      case of temporal contrast sensitivity and temporal acuity the results from these
      tests either are conflicting or provide little support for an impairment. As far
      as vision is concerned there is little evidence for a specifically temporal
      deficit.

PMID- 18612876
TI  - Comparison of two patient-controlled analgesia techniques on neuropsychological
      functioning in the immediate postoperative period.
AB  - Pain may contribute to cognitive decline, which is a common complication in the
      early postoperative period. We compared the effects of two common pain management
      techniques, intravenous patient-controlled analgesia (PCA-IV) and patient
      controlled epidural analgesia (PCEA), on cognitive functioning in the immediate
      postoperative period. Patients hospitalized for elective surgery were randomly
      assigned to one of the treatment groups (30 patients per group). A battery of
      objective, standardized neuropsychological tests was administered preoperatively
      and 24 hours after surgery. Pain intensity was also evaluated. Nonoperated
      volunteers served as controls. Patients of the PCA-IV group exhibited
      significantly higher pain scores than did patients of the PCEA group. PCA-IV
      patients exhibited significant deterioration in the postoperative period in all
      the neuropsychological measures, while the PCEA patients exhibited significant
      deterioration only in one cognitive index, compared to controls.

PMID- 18612877
TI  - Use of specific malingering measures in a Spanish sample.
AB  - There are an increasing number of tests available for detecting malingering.
      However, these tests have not been validated for using in Spanish speakers. The
      purpose of this study is to explore the value of three specific malingering tests
      in the Spanish population. This study used a known-groups design, together with a
      group of analog students. The results show that both the Victoria Symptom
      Validity Test and the b Test can be used to detect malingering in Spanish
      population. However, some restrictions must be applied when the Rey 15-Item Test
      is administered and interpreted.

PMID- 18612880
TI  - Pathways to change: the effect of a Web application on treatment interest.
AB  - Most individuals with drinking problems do not receive treatment, generally
      because they do not perceive the need for it. It is difficult to access this
      population of problem drinkers in order to encourage treatment-seeking. A Web
      based program was written, designed to increase motivation for change. The
      program guided non-treatment-seekers through a multi-stage assessment and
      provided them with feedback. The level of interest in treatment was measured pre
      and post-intervention. Compared to baseline, after the intervention,
      significantly more individuals rated themselves "very interested" in
      participating in some form of traditional treatment (19% vs. 28%), and their
      focus on a specific modality increased.

PMID- 18612879
TI  - Effects of naltrexone during the descending limb of the blood alcohol curve.
AB  - The neuropharmacological effects of alcohol are known to vary by limb of the
      blood alcohol curve, yet human laboratory studies of alcoholism pharmacotherapies
      have largely failed to consider limb of intoxication when examining medication
      effects on subjective responses to alcohol. This study examined the effects of
      naltrexone compared to placebo on subjective responses to alcohol at the
      descending limb of the blood alcohol curve following a controlled intravenous
      (IV) alcohol administration. Non-treatment-seeking hazardous drinkers (n = 38)
      completed two double-blind counterbalanced IV alcohol challenge sessions, one
      after taking naltrexone (50 mg) for three days and one after taking a placebo for
      three days. During each session, participants reported on subjective responses to
      alcohol during the descending limb of the blood alcohol curve. Analyses revealed
      significant main effects of naltrexone, reflecting significantly decreased
      alcohol-induced stimulation, craving, vigor, positive mood, and alcohol "high"
      and increased tension as compared to placebo. These findings suggest that
      naltrexone may exert some of its therapeutic effects via alterations to
      experiential aspects of intoxication during the descending limb of alcohol
      intoxication. Additionally, these results highlight the potential utility of
      considering limb of blood alcohol curve when examining the mechanisms of action
      of pharmacotherapies thought to alter subjective responses to alcohol.

PMID- 18612881
TI  - Earlier violent television exposure and later drug dependence.
AB  - This research examined the longitudinal pathways from earlier violent television
      exposure to later drug dependence. African American and Puerto Rican adolescents
      were interviewed during three points in time (n = 463). Exposure to violent
      television programs in late adolescence predicted exposure to violent television
      programs in young adulthood, which in turn was related to tobacco/marijuana use,
      nicotine dependence, and later drug dependence. Some policy and clinical
      implications suggest regulating the times when violent television programs are
      broadcast, creating developmentally targeted prevention/treatment programs, and
      recognizing that watching violent television programs may serve as a cue
      regarding increased susceptibility to nicotine and drug dependence.

PMID- 18612882
TI  - Contingent reinforcement of personal goal activities for adolescents with
      substance use disorders during post-residential continuing care.
AB  - Contingency management (CM) is efficacious in improving outcomes of substance
      abusing patients, but CM studies are relatively rare in adolescents. CM
      approaches can reinforce both abstinence and adherence to treatment-related goal
      areas. This paper describes 1,739 different activities in 10 goal areas (e.g.,
      education, family/friends, and social/recreational) chosen by 86 adolescents who
      were participating in a multiple week CM study that reinforced both abstinence
      and adherence with goal-related activities. The mean activities selected was 20,
      and the mean completed was 13. Overall, 1,114 or 64% of chosen activities were
      completed. The clinical feasibility of activity incentive programs for
      adolescents is discussed.

PMID- 18612883
TI  - Preliminary study of buprenorphine and bupropion for opioid-dependent smokers.
AB  - In this double-blind, placebo-controlled trial, bupropion (BUPRO, 300 mg/day) was
      compared to placebo (PBO) for the concurrent treatment of opioid and tobacco
      addiction in 40 opioid-dependent smokers stabilized on buprenorphine (BUPRE, 24
      mg/day). Participants received contingent, monetary reinforcement for abstinence
      from smoking, illicit opioids, and cocaine. Significant differences in treatment
      retention were observed (BUPRE+BUPRO, 58%; BUPRE+PBO, 90%). BUPRO treatment was
      not more effective than placebo for abstinence from tobacco, opioids, or cocaine
      in BUPRE-stabilized patients. These preliminary findings do not support the
      efficacy of BUPRO, in combination with BUPRE, for the concurrent treatment of
      opioid and tobacco addiction.

PMID- 18612884
TI  - Gender differences in self-reported drinking-induced disinhibition of sexual
      behaviors.
AB  - Sex and drinking go hand-in-hand in Western societies. Men also tend to report
      more sexual disinhibition under the influence of alcohol and drugs than women. At
      a vacation resort, we conducted a survey of young men and women regarding self
      reported alcohol-related sexual disinhibition (ARSD), and we administered the
      Drinking-Induced Disinhibition Scale (DIDS). We made several comparisons of
      behavioral patterns using the ARSD scale of the DIDS for each gender: kissing or
      having sex vs. no sexual contact, or having sex versus kissing or no contact. In
      general, men reported more ARSD than women. Men who reported either kissing or
      having sex the night before reported significantly more ARSD than men not
      reporting either kissing or having sex. Women who had had sex the night before
      reported more ARSD than women who had either kissed or not reported any sexual
      contact on the night before, but women who had kissed did not differ from women
      who had not had any sexual contact. We suggest that while the DIDS scale of
      alcohol-related sexual disinhibition is a valid instrument, gender bias exists.
      In conclusion, the DIDS does measure the constructs that it sets out to measure.
      However, significant gender differences do exist and appear to go beyond
      differences in actual behavior in terms of sexual disinhibition. Men and women
      describe themselves differently when they describe sexual behavior in general,
      even when they report similar recent behavior, and we suggest that these
      differences at least partly reflect sexual stereotypes.

PMID- 18612885
TI  - Effectiveness of community-based treatment for problem gambling: a quasi
      experimental evaluation of cognitive-behavioral vs. twelve-step therapy.
AB  - With the increasing availability of gambling throughout North America, there is
      interest in developing more effective treatments. This study compares the
      effectiveness of two brief outpatient treatments for problem gambling: eight
      sessions of Cognitive-Behavioral Therapy (n = 65) and eight sessions of a twelve
      step treatment-oriented approach based on the first five steps of Gamblers
      Anonymous (n = 61). There were no baseline group differences on gambling-relevant
      variables. Twelve months post-treatment showed no group differences on key
      gambling variables (eg, frequency, abstinence rates, money wagered) in an
      analysis of completers. Participants who attended more sessions and chose an
      initial abstinent treatment goal appeared to achieve better outcomes.

PMID- 18612886
TI  - Infrequent illicit methadone use among stimulant-using patients in methadone
      maintenance treatment programs: a national drug abuse treatment clinical trials
      network study.
AB  - We sought to determine the prevalence, patterns, and correlates of past-month
      illicit methadone use and history of regular illicit use among stimulant-using
      methadone maintenance treatment patients. We obtained self-reported information
      on illicit methadone use from 383 participants recruited from six community-based
      methadone maintenance programs. Overall, 1.6% of participants reported illicit
      use in the past month, and 4.7% reported a history of regular use. Younger age
      and history of outpatient psychological treatment were associated with increased
      odds of past-month illicit use. Illicit methadone use among patients in
      maintenance programs is infrequent; however, a number of factors may increase
      risk of illicit use.

PMID- 18612887
TI  - Systematic assessment of gamma hydroxybutyrate (GHB) effects during and after
      acute intoxication.
AB  - We adapted and tested a previously published questionnaire battery eliciting
      sensory and cognitive symptoms during (acute) and immediately after (post-acute)
      GHB intoxication. Studying 125 GHB users, we assessed the instrument's internal
      consistency using Cronbach's alpha (CA) and responsiveness to change comparing
      acute and post-acute symptoms. The final 14-item battery demonstrated good
      internal consistency (CA >or= 0.85, both acute and post-acute). The median
      symptom score (possible range 0-64) was 30 (acute) and 6 (post-acute; difference
      p < 0.001). This modified substance-specific symptom battery, which is easily
      administered, demonstrated excellent performance characteristics. It can be used
      to study GHB and, potentially, related drugs of abuse.

PMID- 18612888
TI  - Sex differences in the heritability of alcohol problems.
AB  - Genetic factors may have a role in defining more coherent clinical phenotypes and
      subtypes in the DSM-V. Research has demonstrated that there are gender
      differences in the patterns of alcohol consumption, specific symptom endorsement,
      withdrawal effects, and rates of alcohol use disorders (AUD). We examined the sex
      specific heritability of diagnostic symptoms for alcohol-related problems in a
      community-based sample of twin pairs (males: n = 519; females: n = 613) using a
      biometrical analytic strategy to estimate the genetic and environmental
      components of AUD symptoms. Five of the seven symptoms of alcohol problems
      demonstrated sex-differences in heritability. Three of the seven symptoms
      examined had significant heritability in female twins only: "increased risk of
      injury or harm," "emotional problems related to drinking," and "the desire to
      drink." In males, a different pattern was observed, with four of the seven
      examined symptoms demonstrating heritability: "Increased chance of injury or
      harm," "spending more time using alcohol or getting over its effects," "using
      larger amounts for longer periods of time than intended," and "the need to use
      more alcohol to get the same effect." These data suggest that alcohol problems in
      females and males may be etiologically distinct, and that diagnostic criteria and
      therapeutics might be enhanced if these sex differences were taken into
      consideration.

PMID- 18612890
TI  - Substance abuse and domestic violence interventions: the need for theoretical
      based research.

PMID- 18612892
TI  - Daily sessions of transcranial magnetic stimulation to the left prefrontal cortex
      gradually reduce cocaine craving.

PMID- 18612891
TI  - A case of zolpidem dependence successfully detoxified with clonazepam.

PMID- 18612893
TI  - Asthma 2008: targeting immunoglobulin E to achieve disease control.
AB  - Traditionally, practice guidelines have recommended a step-wise approach to
      treatment based on asthma severity and lung function. However, increasing
      evidence suggests that asthma may not be adequately controlled in many patients
      with moderate-to-severe disease despite aggressive therapy, and that regularly
      evaluating the level of asthma control achieved in individual patients may be
      more effective than disease severity in guiding treatment decisions. This is
      reflected in updated asthma guidelines from the National Asthma Education and
      Prevention Program, which advocate regular assessment of asthma control in terms
      of the current impairment and future risk associated with the disease. Guideline
      recommended options for patients with persistent, moderate-to-severe
      immunoglobulin E (IgE)-mediated asthma have recently been enhanced by the
      inclusion of omalizumab. This change is based on growing evidence for the central
      role of IgE in airway inflammation and asthma and the clinical effectiveness of
      blocking IgE with omalizumab, a recombinant humanized monoclonal antibody.
      Omalizumab significantly reduced asthma exacerbations and improved lung function
      and symptoms in randomized controlled studies of patients inadequately controlled
      on inhaled corticosteroids plus long-acting beta(2)-agonist therapy; these
      benefits for reducing asthma impairment and risk were maintained during steroid
      dose reductions. Omalizumab is well tolerated, although patients should be
      monitored for possible rare anaphylactic reactions.

PMID- 18612894
TI  - Nurse-led care for asthma at primary level in rural sub-Saharan Africa: the
      experience of Bafut in Cameroon.
AB  - BACKGROUND AND PURPOSE: Asthma is an important health condition in sub-Saharan
      Africa, with major gaps in clinical care. The aim of this project was to
      implement nurse-led care for asthma in rural Cameroon. METHODS: We set-up a nurse
      led structured management program for asthma in Bafut rural health district in
      Cameroon from 1998 to 2000. After an initial phase of intensive medical
      supervision, nurses were offered to run the clinics independently. Patients were
      monitored for all-cause mortality, hospitalizations, and control of asthma
      attacks. RESULTS: At the final evaluation, 87 (73.4% women) were registered in
      the two pilot clinics. They were 4 to 92 years of age (median 51) and had been
      diagnosed with asthma for 0 to 40 years. The median duration of follow-up was 5
      months (range 1-20) and patients attended on average 3 visits (range 1 to 14).
      During follow-up, a 66-year-old participant died and 170 emergency hospital
      admissions/consultations were recorded in 34 participants, 82.3% of them being
      women. Overall there was a significant downward trend in the number of days/month
      with attacks with the duration of follow-up, and at the last visit most patients
      had improved compared with the initial visit. This trend was apparent in most
      subgroups of participants. Hospital admission before baseline visit was a
      predictor of hospital admission during follow-up, hazard ratio (95% confidence
      interval) 3.20 (1.30-7.91), p = 0.012. CONCLUSIONS: The program was well received
      by the community at large. A marked improvement was observed for most patients as
      substantiated by the reduction in the number of asthma attacks. Trained nurses
      are a good alternative for the management of asthma in a resource-limited
      context.

PMID- 18612895
TI  - Prognosis of adult asthma after normalization of bronchial hyperresponsiveness by
      inhaled corticosteroid therapy.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) are the most effective anti
      inflammatory drugs for adult asthma and can improve not only clinical symptoms
      but also bronchial hyperresponsiveness (BHR). However, the prognosis of adult
      asthma has not been well studied, and it remains to be elucidated precisely how
      long treatment with ICSs should be continued once clinical remission is achieved.
      OBJECTIVES: We examined whether ICS use could be withdrawn or reduced without
      exacerbation of disease. METHODS: We retrospectively studied 374 adult patients
      with asthma to determine which factors predicted the elimination or reduction of
      ICS treatment without exacerbations of disease after the achievement of
      normalized BHR to acetylcholine. The patients were classified into three groups:
      Group 1 had symptoms within 6 months of normalization and needed to continue
      therapy; group 2 received the equivalent of >or= 400 microg fluticasone
      propionate until BHR normalization, did not have symptoms in the 6 months after
      normalization, and then had their doses of ICSs halved; and group 3 received the
      equivalent of <or= 200 microg fluticasone propionate at an enrollment, did not
      have symptoms in the 6 months after normalization, and then had all ICSs
      withdrawn. The primary outcome measure was the presence of clinical symptoms. We
      used multiple logistic regression and a Kaplan-Meier analysis to analyze the
      factors predicting remission. RESULTS: Twenty-nine patients in group 3 remained
      asymptomatic for more than 30 months (mean 47.1 +/- 12.4 months) after
      discontinuing ICS therapy. The predictive markers of remission were low levels of
      eosinophils in the sputum, high %V(50) at the first hospital visit, and the need
      for only a low daily dose of ICS to induce normalized BHR. Conversely, patients
      with severe BHR at the first hospital visit, low %FEV(1) at normalized BHR, and a
      need for high-dose ICSs to reach normalized BHR could not reduce or discontinue
      treatments. CONCLUSION: Some adult patients with asthma whose BHR is normalized
      by ICS therapy can achieve remission from disease exacerbation after
      discontinuation of ICSs. However, patients with severe asthma or asthma of long
      duration may not achieve remission even if their BHR is normalized.

PMID- 18612896
TI  - Variations in exhaled nitric oxide in children with asthma during a 1-week stay
      in a mountain village sanatorium.
AB  - Knowing about spontaneous variations in the fractional concentration of exhaled
      nitric oxide (FE(NO)) could improve monitoring of airway inflammation in
      asthmatic children. We aimed to assess FE(NO) variations (expiratory flow 50
      mL/sec) in subjects maintained in similar environmental conditions. We tested
      spirometry and FE(NO) in symptom-free asthmatic children (9 corticosteroid-naive,
      8 corticosteroid-treated) during a 1-week stay in a countryside sanatorium and in
      their healthy relatives (n = 12) staying in the immediate neighborhood on summer
      holiday (total 29 children, M/F:14/15, 5.8-16.8 yrs). Testing sessions were
      repeated every 12 hours (8:00 am, 8:00 pm) for 2 days and again on day 7.
      Measurements were defined as reproducible when they agreed with an intraclass
      correlation coefficient (ICC) above 0.60; deviation from mean differences was
      assessed by the coefficient of repeatability (CR = 2 SD). Lung function remained
      constant throughout the week in all groups. Baseline FE(NO) levels in
      corticosteroid-naive asthmatic children tended to decrease at the end of the week
      (from 13.9 ppb, 95% CI 12.2-19.1 to 9.2 ppb, 95% CI 5.8-15.9, p = 0.057). No
      differences were found between nocturnal and diurnal FE(NO). Within-session
      reproducibility for two FE(NO) measurements was high (ICC 0.99 in all groups and
      CR, 0.9 to 1.3 ppb). Between-session FE(NO) reproducibility at 12 hours and 24
      hours was still high for each group but decreased markedly after 6 days in
      corticosteroid-naive asthmatic children (ICC 0.79 and CR 9.6 ppb at 24 hours vs.
      ICC 0.13 and CR 20.8 ppb after 6 days), whereas it decreased slightly in
      corticosteroid-treated asthmatics (from ICC 0.89 and CR 3.1 ppb to ICC 0.88 and
      CR 3.0 ppb) and healthy children (from ICC 0.79 and CR 4.8 ppb to ICC 0.65 and CR
      5.7 ppb). In conclusion, in healthy subjects and in asthmatic children receiving
      therapy with inhaled corticosteroids (but not in corticosteroid-naive subjects),
      FE(NO) measurements are reproducible across a week.

PMID- 18612897
TI  - Illness perceptions about asthma are determinants of outcome.
AB  - This article reviews an emerging area of research on patients with asthma:
      namely, illness perceptions and their relationships with various aspects of
      outcome. The article briefly introduces the Common Sense Model, outlining the
      relevance of how "lay" patients conceptualize symptoms, illness, and treatment.
      On the basis of a comprehensive literature search, nine empirical studies
      illustrating the relationships between illness perceptions and outcomes are
      discussed. It is concluded that further research should focus on assessing asthma
      specific illness and treatment beliefs. Also, given the effects of intervention
      studies in illness perceptions in other patient categories, it is recommended
      that serious consideration be given to intervention studies focusing on eliciting
      and changing illness perceptions in asthma patients, especially in those whose
      self-management seems to be inadequate.

PMID- 18612898
TI  - Parenting asthmatic children: identification of parenting challenges.
AB  - Asthma is the most common chronic illness of childhood, affecting up to 14% of
      children. Poor asthma management and non-adherence to treatment regimens are a
      pervasive problem in this population and are related to exacerbation of symptoms.
      Effective management of pediatric asthma involves a complex set of interactions
      between the parent and child, yet there is a paucity of literature examining
      these interactions. The main purpose of this study was to identify the child
      behavior and asthma management tasks parents experience difficulty with. It was
      hypothesized that the more asthma behavior problems reported, the more problems
      parents experience in asthma management tasks. Participants in this study were
      255 parents of 2-to 10-year-old asthmatic children, recruited via an
      advertisement placed in school newsletters throughout Australia. Results
      indicated that the most problematic child asthma behaviors were oppositional
      behavior, hyperactivity, and aggression, and anxiety was also identified by
      parents as a concern. The main problematic asthma parenting tasks were entrusting
      the school, entrusting caregivers, identifying unique symptoms, and identifying
      and avoiding triggers. More problem asthma behaviors were associated with higher
      levels of parenting difficulty and more general levels of behavior problems.
      Parents who reported more dysfunctional parenting styles reported more
      difficulties with their child's asthma behavior. Based on the results it is
      suggested that an appropriate parenting intervention program would target basic
      behavioral management skills, in addition to applying these behavior management
      principles to asthma management.

PMID- 18612899
TI  - Body mass index and childhood asthma: a linear association?
AB  - Our objective was to characterize the association between body mass index (BMI)
      and childhood asthma while adjusting for individual and neighborhood
      socioeconomic factors. Data were obtained from 3,804 students 10 to 11 years of
      age in Nova Scotia, Canada. Asthma was defined as parent-reported doctor
      diagnosed asthma or bronchitis. Smoothed curves suggested a linear association
      between BMI and asthma with a 6 % increase in prevalence per unit increase of
      BMI. This association was independent of allergies, sex, and socioeconomic
      factors. Girls from socioeconomically disadvantaged neighborhoods were less
      likely to be asthmatic as were boys from well-educated and wealthy families.

PMID- 18612900
TI  - When should a reversibility test be performed on patients with early stages of
      asthma and normal spirometry?
AB  - Subjects with bronchial asthmatic symptoms, forced expiratory volume in 1 second
      (FEV(1)) and FEV(1)/forced vital capacity [FVC] > 80% could show a positive
      reversibility test with salbutamol in about 25% of the cases. The aim of this
      study was to evaluate if a limit functional value for spirometry exists where a
      reversibility test using salbutamol, over this limit, is not necessary to confirm
      the diagnosis of asthma. Four hundred patients (mean age 31.12 +/- 10.99) with
      asthmatic symptoms and normal spirometry (mean FEV(1) 96.06 +/- 11.82%, mean
      FEV(1)/FVC 98.89 +/- 6.03%) were recruited. The number of subjects with
      reversible airflow obstruction (RAO) was evaluated using the following different
      criteria of reversibility: FEV(1) and FVC >or= slant 12%, peak expiratory flow
      (PEF) >or= slant 15%, FEF(25 -75) >or= slant 35%, and at least one of these
      (ANY). In subjects with baseline FEV(1) > 100% (150 patients), 26 (17.3%)
      patients showed a FEV(1) increase > 12% and, among the criteria used, 45 patients
      (30%) showed ANY. In subjects with baseline FEV(1)/FVC > 100% (204 patients), 36
      patients (17.6%) showed a FEV(1) increase > 12% and 53 patients (26.8%) showed
      ANY. In subjects with baseline FEF(25 -75) > 70% (209 patients), 26 (12.44%) and
      49 (23.44%) patients, respectively, showed an increase in FEV(1) > 12%, and ANY.
      In 56 patients with baseline cut-offs (evaluated together) FEV(1) > 100%,
      FEV(1)/FVC > 100% and FEF(25-75) > 70%, 10 patients (17.85%) showed a RAO with
      ANY. FEV(1) > 121% or FEV(1)/FVC > 110.8% or FEF(25 -75) > 110% were cut-off
      values identified in this study where no RAO subjects were found over these
      limits. In conclusion, baseline FEV(1) > 100%, FEV(1)/FVC > 100% and FEF(25 -75)
      > 70% cannot be considered cut-offs where it is not necessary to perform a
      reversibility test with a bronchodilator over these limits. It is improbable to
      find a positive reversibility test using salbutamol in patients with asthmatic
      symptoms and FEV(1) > 121% or FEV(1)/FVC > 110.8% or FEF(25 -75) > 110% to
      confirm the diagnosis of asthma.

PMID- 18612901
TI  - Seasonal changes in platelet activity in pollen-induced seasonal allergic
      rhinitis and asthma.
AB  - BACKGROUND: Previously we reported that patients sensitized to pollen-allergens
      who had seasonal allergic rhinitis and seasonal asthma may show increased plasma
      levels of platelet activation markers during grass pollen season. OBJECTIVE: To
      find out whether the pattern of platelet activity measured by plasma PF-4 level
      in the same group of patients changed off-season compared with the pollen season
      as well as in comparison with healthy control subjects. METHODS: Off-pollen
      season, plasma PF-4 level was determined by enzyme-linked immunosorbent assay
      (ELISA) in 16 grass pollen allergic patients who had seasonal allergic rhinitis
      and seasonal asthmatic symptoms (none of them had any history of allergic
      diseases outside the season) and in 29 healthy nonatopic subjects. RESULTS:
      Plasma PF-4 level in the patients off-pollen season was significantly lower as
      compared with the season and did not differ significantly as compared to the
      healthy subjects. CONCLUSIONS: This observation taken along with our previous
      results indicates that patients with seasonal allergic rhinitis and asthma
      symptoms may have an increased circulating platelet activation, yet this
      phenomenon disappears in the asymptomatic period of the disease. This might
      indicate that platelet activation within the systemic circulation is an important
      factor in the development of seasonal allergic airway inflammation.

PMID- 18612902
TI  - Mental, emotional, and social problems among school children with asthma.
AB  - OBJECTIVES: To use representative population chronic disease and risk factor data
      to investigate the relationship between asthma and social factors in school-age
      children. METHODS: Representative cross-sectional data for children 5 to 15 years
      of age were collected from 2002 to June 2007 (n = 4,611) in the South Australian
      Monitoring and Surveillance System (SAMSS) using Computer-Assisted Telephone
      Interviews (CATI). Univariate and multivariate analyses were conducted to
      investigate the variables that were associated with asthma among children.
      RESULTS: The overall prevalence of self-reported asthma among children 5 to 15
      years of age was 18.6% (95% CI = 17.5-19.8). Children with asthma were more
      likely to have been treated for a mental health problem, have been unhappy at
      school, have been absent from school in the last month, have fair or poor overall
      health and well-being, have ongoing pain or chronic illness, and less likely to
      have a group of friends to play with. Asthma was also more prevalent among males
      and less likely to occur in children from households where the gross annual
      income was greater than $AU80,000. CONCLUSIONS: Children with asthma were more
      likely to be treated for a mental health problem and demonstrate more negative
      social outcomes as well as poorer overall health and well-being. Asthma
      management plans need to be sensitive to these psychosocial factors for adequate
      care of these vulnerable young patients.

PMID- 18612903
TI  - Persistent impact of cigarette smoking on asthma.
AB  - OBJECTIVE: In the present study we assessed the impact of former cigarette
      smoking on asthma control and treatment effectiveness. METHODS: A total of 104
      patients with uncontrolled asthma were included in the study. The group of former
      smokers consisted of 33 subjects, whereas the never smokers group consisted of 71
      subjects of similar age and gender. Spirometry, classification of asthma
      severity, and control were assessed according to Global Initiative for Asthma
      (GINA) guidelines. Quality of life was measured with the use of the Saint George
      Hospital Respiratory Questionnaire (SGHRQ). RESULTS: Asthma was more severe in
      the group of former smokers both before and after treatment; p < 0.001. Severe
      asthma (OR 7.8 CI 2.8-21.9) and cigarette smoking (OR 3.5 CI 1.3-9.2) were
      associated with difficulties in asthma control achievement. Total quality of life
      significantly improved in the group of non-smokers; p = 0.02, whereas in former
      smokers this effect was not significant; p > 0.05. CONCLUSION: Cigarette smoking
      has a persistent, dose-dependent, negative impact on the response to treatment in
      patients with uncontrolled asthma even after smoking cessation. Smoking cessation
      should remain the ultimate goal in treatment of asthmatic patients. More efforts
      should be undertaken to decrease smoking initiation, especially in teenagers.

PMID- 18612904
TI  - Longitudinal patterns of predominant asthma disease activity in pediatric
      patients enrolled in an asthma-specific disease management program.
AB  - To determine if patterns of predominant asthma disease activity are more closely
      related than baseline asthma severity to measures of morbidity (acute asthma
      attack, emergency room visit/hospitalization, missed school days, and/or steroid
      burst). Retrospective analysis was performed for inner-city Los Angeles asthmatic
      children (3 to 18 years of age) during their first year of enrollment in an
      asthma-specific disease management program. All measures of morbidity were more
      closely related to patterns of predominant disease activity than baseline
      severity. We conclude that patterns of predominant disease activity are a more
      significant predictor of asthma morbidity than is baseline severity.

PMID- 18612905
TI  - Disease variability in asthma: how do the patients respond?--and why?
AB  - BACKGROUND AND AIM: Asthma is a variable disease, and therapy should be tailored
      accordingly. The aim of this study was to explore patterns of self-management in
      response to disease variability in adult asthmatics. METHODS: Adult asthmatics (n
      = 509), recruited through a web-based panel, answered a questionnaire concerning
      asthma knowledge, compliance, and treatment, including specified treatment
      options, through the Internet. RESULTS: Two-thirds of the patients on inhaled
      corticosteroids (ICS) stepped-up and down their daily dose without prior contact
      to their doctor, and more than 50% took less ICS than prescribed during periods
      with fewer symptoms. In case of deterioration, 57% of the patients would only
      increase their reliever medication, whereas 23% would also increase their
      controller medication, although 59% were instructed by their doctor to do so. The
      self-perceived severity of asthma (graded as mild, moderate or severe) was not
      associated with the patients' response pattern. The preferred treatment strategy,
      differing primarily with regard to dosing and timing of controller medication,
      was associated with feeling safe about self-adjustment of controller medication
      (p < 0.001), but not with self-reported knowledge of asthma (p > 0.5).
      CONCLUSION: In case of deterioration, the majority of adult asthmatics only
      increase their reliever medication, although instructed by their doctors also to
      increase their controller medication. Furthermore, the patients' preferred
      strategy for management of disease variability seems not to be driven by their
      knowledge of the disease.

PMID- 18612906
TI  - Severe exacerbations in children with mild asthma: characterizing a pediatric
      phenotype.
AB  - BACKGROUND: NHLBI guidelines classify asthma in children as intermittent, mild
      persistent, moderate persistent, and severe persistent asthma based on baseline
      symptoms and pulmonary function. However, this may not capture the spectrum of
      asthma in children, since even mild baseline disease can have significant effects
      on quality of life. Our objective was to describe a population of children with
      mild asthma admitted to the ICU with severe exacerbations. METHODS: We examined
      data from all children with asthma who were admitted to the ICU with an acute
      exacerbation between April 1997, and December 2006. Children were defined as
      having mild asthma if their disease was classified as intermittent or mild
      persistent according to NHLBI criteria. RESULTS: Of the 298 children admitted to
      the ICU with asthma, 164 (55%) were classified as having mild baseline asthma.
      Compared with children with more severe baseline asthma, mild asthmatic children
      were younger and less likely to have been previously admitted to the hospital for
      asthma. Other demographics, including admission severity of illness, gender, and
      prevalence of overweight, were similar in the two groups. There were no
      differences between the groups in ICU length of stay, hospital length of stay or
      types of therapies received. Thirteen children with mild asthma were intubated,
      although less frequently than those with more severe disease. CONCLUSIONS:
      Children with mild asthma have severe exacerbations. This suggests that chronic
      asthma severity does not necessarily predict asthma phenotypes during acute
      exacerbations.

PMID- 18612907
TI  - Primary and secondary prophylaxis to the use of inhaled glucocorticoid in primary
      health care.
AB  - OBJECTIVES: To investigate the extent of inhaled glucocorticoid (IGC) treatment
      in general and to what extent general practitioners (GPs) manage the risk of
      glucocorticoid-induced osteoporosis. METHOD: A questionnaire was sent to all
      3,617 GPs in Denmark. RESULTS: The results are divided into criteria for
      recommending prophylaxis with calcium and vitamin D for patients in actual IGC
      treatment, routine examinations for osteoporosis before starting asthma or
      chronic obstructive pulmonary disease (COPD) treatment with IGC, and criteria for
      starting anti-osteoporotic treatment (bisphosphonates + calcium + vitamin D) for
      patients in IGC treatment. A total of 535 questionnaires were eligible for
      evaluation and covered almost 25% of the Danish population. In general, the
      questionnaires documented that physicians do not use primary nor secondary
      prophylaxis in their patients treated with IGC with or without risk factors of
      osteoporosis. CONCLUSION: More studies are warranted to verify the effects of IGC
      treatment on bone health and the importance of prophylaxis to prevent
      osteoporosis in IGC-treated patients before outlining specific recommendations
      for the management of the disease.

PMID- 18612908
TI  - Is surface orientation a determinant for colonisation patterns of vagile and
      sessile macrobenthos on artificial reefs?
AB  - In order to examine how substratum colonisation can affect community structure, a
      1-year study was conducted at the Faro/Ancao artificial reef (Algarve, Portugal).
      In the study of hard substratum communities, motile species are usually neglected
      and only the conspicuous species are taken into account. Therefore, the
      development of vagile and sessile components of the epibiotic community were
      analysed separately. Differences between assemblages on horizontal surfaces, but
      not on vertical surfaces, were detected. Multivariate analysis detected
      differences in macrobenthic community structure either considering sessile or
      motile components. However, significant differences were only detected for vagile
      fauna. Moreover, this study suggests that for hard substratum communities,
      analysis of the vagile fauna is important and should be taken into account in the
      functioning of the artificial raft.

PMID- 18612909
TI  - Physicochemical properties of the nucleoside prodrug R1626 leading to high oral
      bioavailability.
AB  - The nucleoside analog R1479 is a potent and highly selective inhibitor of NS5b
      directed hepatitis C virus (HCV) RNA polymerase in vitro. Because of its limited
      permeability, lipophilic prodrugs of R1479 were screened. Selection of the
      prodrug involved optimization of solubility, permeability, and stability
      parameters. R1626 has dissociation constant, intrinsic solubility, log partition
      coefficient (n-octanol water), and Caco-2 permeability of 3.62, 0.19 mg/mL, 2.45,
      and 14.95 x 10(-6) cm/s, respectively. The hydrolysis of the prodrug is
      significantly faster in the Caco-2 experiments than in hydrolytic experiments,
      suggesting that the hydrolysis is catalyzed by enzymes in the cellular membrane.
      Using GastroPlus, the physical properties of R1626 successfully predict the dose
      dependence of the pharmacokinetics in humans previously studied. The program
      predicts that if the particle size of R1626 is less than 25 microm, it will be
      well absorbed. Prodrugs with a solubility of greater than 100 microg/mL and
      permeability in the Caco-2 assay greater than 3 x 10(-6) cm/s are expected to
      achieve a high fraction absorbed.

PMID- 18612910
TI  - Paclitaxel-loaded microparticles for intratumoral administration via the TMT
      technique: preparation, characterization, and preliminary antitumoral evaluation.
AB  - In our pursuit to develop suitable therapeutic particulate systems for
      intratumoral delivery by the targeted multi-therapy (TMT) technique, we describe
      the preparation of paclitaxel-loaded poly(D,L-lactic-co-glycolic) acid (PLGA)
      microparticles (MPs) (drug loading 35-38%, wt/wt; size 0.7-5 microm). Magnetite
      (15%, wt/wt) was also incorporated in some preparations for a future magnetic
      resonance imaging (MRI)-guided delivery. X-ray diffraction (XRD) and differential
      scanning calorimetry (DSC) experiments showed that paclitaxel was not
      encapsulated in its initial crystalline form. The paclitaxel in vitro release
      pattern showed a biphasic tendency with a burst effect followed by a sustained
      release (28% released amount after 1 month), which was accompanied with MP
      erosion and degradation signs as confirmed by scanning electronic microscopy
      (SEM) micrographs. The paclitaxel-loaded MPs demonstrated a dose-dependent
      antitumor effect on human uterine cancer cells, with an IC(50) value relatively
      close to that of commercial Taxol. This paclitaxel delivery system represents a
      potent antiprofilerative and radiosensitizer agent for intratumoral
      administration via the TMT technique.

PMID- 18612911
TI  - Preparation, characterization, and bioavailability of ursodeoxycholic acid
      phospholipid complex in vivo.
AB  - The aim of this study was to prepare ursodeoxycholic acid-phospholipid complex
      (UDCA-PLC) to enhance oral bioavailability of UDCA, and the physicochemical
      properties of the complex were studied. Compared with those of UDCA tablet after
      oral administration in rats, the main pharmacokinetic characteristics and
      bioavailability of UDCA-PLC orally administered were evaluated. Tetrahydrofuran
      was used as a reaction medium, UDCA and phospholipids were resolved into the
      medium, and UDCA-PLC was formed after the organic solvent was evaporated off
      under vacuum condition. The physicochemical properties of the complex were
      evaluated using scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction,
      particle size distribution analysis, and n-octanol/water partition coefficient
      (P) study. The blood concentrations of UDCA-PLC and UDCA tablet at different time
      points after oral administration in rats were assayed by high-performance liquid
      chromatography (HPLC) after derivatization. The pharmacokinetic parameters were
      computed by software program 3p87. The X-ray diffraction and DSC studies showed
      that UDCA and phospholipids in the UDCA-PLC were combined by noncovalent bond,
      not forming a new compound, and n-octanol/water partition coefficient (P) of UDCA
      PLC was effectively enhanced. The mean serum concentration-time curves of UDCA
      after oral administration of UDCA-PLC and UDCA tablet in rats were both in
      accordance with open two-compartment model. Pharmacokinetic parameters of UDCA
      tablet and the PLC in rats were T(max) 1.9144 and 1.5610 h, C(max) 0.0576 and
      0.1346 microg/mL, and AUC(0-infinity) 4.736 and 11.437 microg h/mL, respectively.
      The bioavailability of UDCA in rats was significantly different (p < .05)
      compared with those of UDCA tablet after administration. The UDCA-PLC would be
      more prospective formulation in future.

PMID- 18612912
TI  - Development of nitrendipine controlled release formulations based on SLN and NLC
      for topical delivery: in vitro and ex vivo characterization.
AB  - The aim of the investigation is to develop solid lipid nanoparticles (SLN) and
      nano-structured lipid carrier (NLC) as carriers for topical delivery of
      nitrendipine (NDP). NDP-loaded SLN and NLC were prepared by hot homogenization
      technique followed by sonication, and they were characterized for particle size,
      zeta potential, entrapment efficiency, stability, and in vitro release profiles.
      Also the percutaneous permeation of NDPSLN A, NDPSLN B, and NDPNLC were
      investigated in abdominal rat skin using modified Franz diffusion cells. The
      steady state flux, permeation coefficient, and lag time of NDP were estimated
      over 24 h and compared with that of control (NDP solution). The particle size was
      analyzed by photon correlation spectroscopy (PCS) using Malvern zeta sizer, which
      shows that the NDPSLN A, NDPSLN B, and NDPNLC were in the range of 124-300 nm
      during 90 days of storage at room temperature. For all the tested formulations
      (NDPSLN A, NDPSLN B, and NDPNLC), the entrapment efficiency was higher than 75%
      after 90 days of storage. The cumulative percentage of drug release at 24 h was
      found to be 26.21, 30.81, and 37.52 for NDPSLN A, NDPSLN B, and NDPNLC,
      respectively. The results obtained from in vitro release profiles also indicated
      the use of these lipid nanoparticles as modified release formulations for
      lipophilic drug over a period of 24 h. The data obtained from in vitro release
      from NDPSLN A, NDPSLN B, and NDPNLC were fitted to various kinetic models. High
      correlation was obtained in Higuchi and Weibull model. The release pattern of
      drug is analyzed and found to follow Weibull and Higuchi equations. The
      permeation profiles were obtained for all formulations: NDPSLN A, NDPSLN B, and
      NDPNLC. Of all the three formulations, NDPNLC provided the greatest enhancement
      for NDP flux (21.485 +/- 2.82 microg/h/cm(2)), which was fourfold over control
      (4.881 +/- 0.96 microg/h/cm(2)). The flux obtained with NDPSLN B (16.983 +/- 2.91
      microg/h/cm(2)) and NDPNLC (21.485 +/- 2.82 microg/h/cm(2)) meets the required
      flux (16.85 microg/h/cm(2)).

PMID- 18612913
TI  - Ocular poloxamer-based ciprofloxacin hydrochloride in situ forming gels.
AB  - The purpose of this study was to develop poloxamer-based in situ gelling
      formulations of ciprofloxacin hydrochloride (HCl) aiming at prolonging corneal
      contact time, controlling drug release, enhancing ocular bioavailability, and
      increasing patient compliance. The in situ forming gels were prepared using
      different concentrations of poloxamer 407 (P407) and poloxamer 188 (P188).
      Mucoadhesives such as hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl
      cellulose (HEC) were added to the formulations to enhance the gel bioadhesion
      properties. The prepared formulations were evaluated for their in vitro drug
      release, sol-gel transition temperature, rheological behavior, and mucoadhesion
      force. The in vivo antimicrobial efficacy of selected ciprofloxacin HCl in situ
      gelling formulations was studied on infected rabbit's eyes and compared with that
      of the marketed conventional eye drops. The gelation temperature of the prepared
      formulations ranged from 28.00 to 34.03 degrees C. Increasing the concentrations
      of P407, HPMC, and HEC increased the viscosity and mucoadhesion force of the
      preparations and decreased the in vitro drug release. Ciprofloxacin HCl in situ
      forming gel formulae composed of P407/P188/HPMC (18/13/1.5%, wt/wt), and
      P407/P188/HEC (18/13/0.5%, wt/wt) showed optimum release and mucoadhesion
      properties and improved ocular bioavailability as evidenced by an enhanced
      therapeutic response compared with the marketed conventional eye drops.

PMID- 18612914
TI  - Buccal bioadhesive delivery system of 5-fluorouracil: optimization and
      characterization.
AB  - The objective of this work was to apply the response surface approach in the
      development of buccal bioadhesive tablets of 5-fluorouracil (5-FU). Experiments
      were performed according to a 3(2) factorial design to evaluate the effects of
      two polymers, Gantrez MS-955 (X(1)) and hydroxypropylmethyl cellulose (HPMC) K15M
      (X(2)) on the bioadhesive force, percentage drug release in 8 h (Rel(8 h)), time
      taken for 50% drug release (t(50%)), and diffusion coefficient (n). The effect of
      the two independent variables on the response variables was studied by response
      surface plots and contour plots generated by the Design Expert software. The
      compatibility between 5-FU and the tablet excipients was confirmed by
      differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR)
      studies. Both the polymers were found to have synergistic effect on bioadhesion
      but the effect of Gantrez was more pronounced. A nonlinear twisted relationship
      was obtained for Rel(8 h) at the intermediate and high levels of the polymers,
      which indicated an interaction between them at the corresponding factor levels.
      Kinetic treatment to the dissolution profiles revealed that the drug release
      ranged from Fickian to anomalous transport, which was mainly dependent on both
      the independent variables. The desirability function was used to optimize the
      response variables, and the observed responses were in agreement with the
      experimental values.

PMID- 18612915
TI  - Effect of dehydration and urea on stability of homosulfamine in solid states.
AB  - In the presence of urea in solid states, the stability of unpulverized
      homosulfamine hydrate (phase I; UHH) is significantly decreased whereas that of
      unpulverized homosulfamine anhydrate (UHA) is not. The stability of UHH is
      decreased slightly more by pulverization (PHH). The major objective of this study
      was to investigate the effects of urea, dehydration, and pulverization on the
      stability of homosulfamine in solid states. Binary mixtures of UHH and urea, PHH
      and urea, and UHA and urea in a ratio of 1:1 (wt/wt) were prepared as physical
      mixtures and were analyzed by scanning electron microscopy (SEM), powder X-ray
      diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy to study
      their appearance and structural changes before and after storage. PXRD analysis
      revealed that physical mixtures comprising UHH and urea and PHH and urea have the
      same diffraction pattern as that of the mixture of UHA and urea after
      preparation. The dehydration rate of the crystal water of UHH was accelerated by
      the presence of urea in addition to pulverization. Moreover, the PXRD patterns of
      the physical mixtures of UHH/urea and PHH/urea were significantly altered during
      storage, whereas that of UHA/urea was not, which was consistent with the SEM and
      FTIR results. The particle shape and appearance of UHH varied significantly as a
      result of pulverization. The stability of homosulfamine was influenced not only
      by the presence of urea and dehydration but also by the surface state and
      particle size of the crystalline form.

PMID- 18612916
TI  - Preparation of a solid dispersion by a dropping method to improve the rate of
      dissolution of meloxicam.
AB  - Application of a solid dispersion system is one of the methods used to increase
      the bioavailability of poorly water-soluble drugs. Adaptation of the dropping
      method from the chemical industry as a formulation procedure may help the scaling
      up process and simplify the formulation of poorly water-soluble compounds.
      Meloxicam (ME), a nonsteroidal anti-inflammatory drug that is poorly soluble in
      water, and polyethylene glycol (PEG) 4000, a water-soluble carrier, were
      formulated by using a dropping method in an attempt to improve the dissolution of
      ME. Pure ME and physical mixtures and tablets of ME-PEG 4000 (1:3 ratio) were
      compared as regards their dissolution with samples formulated by the dropping
      method. The results revealed that the round particles (solid drops) exhibited a
      higher dissolution rate than those of the physical mixtures, tablets, and pure
      ME. Self-modeling curve resolution (SMCR) as a chemometric method was used to
      evaluate X-ray powder diffractometry (XRPD) data. The results demonstrated the
      presence of a new crystalline phase in the solid dispersion, which can help the
      fast and quantitative dissolution from the solid drops. The round particles can
      be adapted to individual therapy by using a distributor.

PMID- 18612917
TI  - Influence of roasting and different brewing processes on the ochratoxin A content
      in coffee determined by high-performance liquid chromatography-fluorescence
      detection (HPLC-FLD).
AB  - A rapid and reliable procedure has been developed for the determination of
      ochratoxin A (OTA) in green and roasted coffee. The method consists of extraction
      of the sample with methanol-5% aqueous sodium hydrogen carbonate/1% PEG8000
      (20:80), followed by immunoaffinity column (IAC) clean-up and, finally, high
      performance liquid chromatography (HPLC) determination with fluorimetric
      detection. Mean recoveries for green and roasted coffee spiked at different
      levels ranging from 94 and 105% were obtained. The limit of determination (S/N =
      3) was 0.032 ng g(-1) and the precision (within-laboratory relative standard
      deviation) was 6%. The method described has been used to assess the influence of
      roasting and different brewing processes on OTA content in commercial lots of
      green and roasted coffee. The results provided evidence that roasting led to a
      significant drop on OTA levels (65-100%). Also, the way coffee is prepared
      affects the OTA content: brewing using a Moka Express (Italian coffee) led to a
      significant reduction of OTA concentration (50-75%) since hot water stays in
      contact with coffee for a short time. On the contrary, Turkish coffee-making
      (infusion for about 10 min) cause poor reduction in OTA.

PMID- 18612918
TI  - Aspirin resistance: myth or major problem?

PMID- 18612919
TI  - Effects of selective and unselective endothelin-receptor antagonists on
      prostacyclin synthase gene expression in experimental pulmonary hypertension.
AB  - OBJECTIVE: Compared to the unselective endothelin (ET) receptor antagonist
      (Bosentan), superior effects of selective ET-A-receptor blockage (Ambrisentan)
      for the treatment of pulmonary hypertension (PH) are expected due to ET-B
      receptor mediated beneficial effects. Our hypothesis was that treatment with
      Ambrisentan leads to an increase in prostacyclin synthase I (PGIS) expression
      compared to Bosentan. MATERIAL AND METHODS: To test this hypothesis, rats were
      treated with either monocrotaline (MCT) only, MCT+Ambrisentan or MCT+Bosentan.
      After 4 weeks, right ventricular systolic pressure (RVSP), pulmonary vascular
      remodelling and right ventricular hypertrophy (RV/(LV+S)) were measured. RESULTS:
      In MCT only treated animals, significantly greater expression of PGIS mRNA was
      found in the lungs compared to control animals, and this was confirmed by
      immunohistochemical analysis indicating increased staining of PGIS in the very
      small pulmonary arteries (17 % greater expression of PGIS mRNA in MCT versus
      control, p = 0.002; Remmele score (RS): 51 versus 102, p = 0.009). Treatment with
      Bosentan resulted in a significantly lower expression of PGIS mRNA compared to
      Ambrisentan and MCT only (7 % versus 18 %, p = 0.003 and 7 % versus 17 %, p =
      0.004). This observation was also confirmed by immunohistochemical analysis (RS
      very small arteries: 45 versus 81, p = 0.003; RS small arteries: 45 versus 108, p
      = 0.014). No difference was observed in RVSP, RV/(LV+S) or pulmonary vascular
      remodelling between the two treatment groups (RVSP: 28 versus 39 mmHg, p = 0.189;
      RV/(LV+S) 0.46 versus 0.48, p = 0.818; medial area: 78.3 % versus 75.2 %, p =
      0.823). CONCLUSIONS: Treatment with Bosentan leads to lower PGIS expression in
      pulmonary arteries compared to Ambrisentan, although the greater PGIS expression
      by Ambrisentan treatment had no benefical effect on pulmonary haemodynamics.

PMID- 18612920
TI  - Circulating oxidized LDL is associated with the occurrence of echolucent plaques
      in the carotid artery in 61-year-old men.
AB  - OBJECTIVE: The aim of this study was to elucidate the relationship between the
      echogenicity of carotid artery plaques and the following risk factors:
      circulating oxLDL, hsCRP, the metabolic syndrome (MetS), and several of the
      traditional cardiovascular (CV) risk factors. MATERIAL AND METHODS: A cross
      sectional population-based study of 513 sixty-one-year-old men. The levels of
      circulating oxLDL were determined in plasma samples by sandwich ELISA utilizing a
      specific murine monoclonal antibody (mAb-4E6). High-sensitivity CRP was measured
      in plasma by ELISA. Plaque occurrence, size and echogenicity were evaluated from
      B-mode ultrasound registrations in the carotid arteries. Plaque echogenicity was
      assessed based on a four-graded classification scale. RESULTS: A higher frequency
      of echolucent carotid plaques was observed with increasing levels of oxLDL and
      systolic blood pressure (p = 0.008 and p = 0.041, respectively). Subjects with
      the MetS had a significantly higher frequency of echogenic plaques than subjects
      without the MetS (p = 0.009). In a multiple logistic regression analysis, oxLDL
      turned out to be independently associated with echolucent carotid plaques.
      CONCLUSIONS: The occurrence of echolucent carotid plaques was associated with
      oxLDL and systolic blood pressure, and oxLDL was associated with echolucent
      carotid plaques independently of systolic blood pressure.

PMID- 18612921
TI  - How to deal with dichotomous tests? Application of a rankit ordinal scale model
      with examples from the Nordic ordinal scale project on screening tests.
AB  - OBJECTIVE: The purpose of this investigation was to improve a rankit ordinal
      model for evaluating and validating dichotomized tests in a prospective Nordic
      project. MATERIAL AND METHODS: The model is based on the assumption that the S
      shaped curve of fractions of positive for increasing concentrations can be de
      convoluted to a histogram and thereby used to calculate the parameters for a ln
      Gaussian distribution. In a Nordic survey, four urine samples with known
      concentrations of hCG (human chorionic gonadotrophin) and nitrites were
      distributed to more than 2500 practitioners' offices. RESULTS: The results are
      presented as parameters (geometric mean and CV) for the components urine-hCG and
      urine-nitrites, together with fractions of positive for clinical critical values
      (5 and 40 IU/L for hCG), for which fractions should be below 0.01 and above 0.99,
      respectively, and 7 micromol/L for nitrites. Furthermore, the concentration
      intervals of varying fractions of positive from 0.01 to 0.99 are estimated as
      grey zones. The parameters and grey zones for different kits are compared. No
      urine-hCG kit fulfilled the low clinical criterion, whereas all fulfilled the
      high criterion. Seven of the eight nitrites kits had fractions of positive above
      0.9 for the company confirmation limit, but varying fractions for the clinically
      important limit of 7 micromol/L (fractions from 0.06 to 0.83). CONCLUSIONS: The
      present model makes it easy to estimate parameters for the kits, and also to
      estimate the fractions of measured positives for specified concentrations. It is
      thus suited for external quality assessment as well as for manufacturers' method
      validation.

PMID- 18612922
TI  - Changes in platelet volume, morphology and RNA content in subjects treated with
      haemodialysis.
AB  - During haemodialysis treatment, blood flows from the body to the extracorporeal
      circuit and vice versa. In this study, pathophysiological defects in platelets
      indicated by alterations in RNA content and aberrations in platelet volume and
      morphology are detected before and during haemodialysis treatment. In subjects
      receiving haemodialysis treatment, qualitative interpretation of platelet
      characteristics with application of light microscopic evaluation reveals only
      19+/-11 % of platelets with appropriate staining density of the granule
      containing cytoplasm. On the contrary, a reference group of apparently healthy
      subjects shows 70+/-12 % platelets with appropriate staining density of the
      granule-containing cytoplasm. During haemodialysis treatment, mean values for
      platelet volume, platelet distribution width and platelet large cell ratio
      demonstrate a tendency to decrease by 10 %, 11 % and 6 %, respectively, from the
      mean initial value to the value at t = 150 min. Reduction of the platelet volume
      parameters just mentioned is hypothesized to be due to platelet degranulation as
      a result of platelet activation.

PMID- 18612924
TI  - Disease activity and disability but probably not glucocorticoid treatment
      predicts loss in bone mineral density in women with early rheumatoid arthritis.
AB  - OBJECTIVES: Osteoporosis is a known complication of rheumatoid arthritis (RA).
      This prospective study aimed to evaluate whether disease activity, disability,
      and glucocorticoid (GC) treatment in early RA were risk factors for loss of bone
      mineral density (BMD). METHODS: We followed 97 women (mean age 58 years), for 24
      months, with a history of RA of less than 12 months. At baseline, 77 women were
      receiving standard treatment with disease-modifying antirheumatic drugs (DMARDs)
      and 20 were receiving no treatment. Risk factors for osteoporosis were recorded.
      Disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, and
      medications were registered at baseline and every 6 months and calculated as
      areas under the curve (AUCs). Femoral neck and lumbar spine BMD were measured at
      baseline and after 2 years and compared to BMD in age- and gender-matched
      controls. Risk factors were analysed by linear regression models. RESULTS: BMD
      loss was comparable to that of age-matched women in both the lumbar spine and the
      femoral neck, although neither was significantly different from baseline. In
      multivariate analyses the AUC for DAS28 was an independent predictor of changes
      in lumbar spine BMD (p = 0.003) and that for HAQ of changes in femoral neck BMD
      (p = 0.018). GC use was not an overall predictor of BMD loss. CONCLUSION: BMD
      loss was predicted by high disease activity and disability but not by GC
      treatment. With the DMARD, GC, hormone replacement therapy (HRT), and
      bisphosphonate treatment strategies used during the study period, the general
      outcome seems favourable concerning loss of BMD in patients with early RA.

PMID- 18612923
TI  - Circulating levels of osteopontin, osteoprotegerin, total soluble receptor
      activator of nuclear factor-kappa B ligand, and high-sensitivity C-reactive
      protein in patients with active rheumatoid arthritis randomized to etanercept
      alone or in combination with methotrexate.
AB  - OBJECTIVE: To determine whether circulating levels of osteopontin (OPN),
      osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-kappa B
      ligand (total sRANKL), and high-sensitivity C-reactive protein (hsCRP) change in
      patients with rheumatoid arthritis (RA) during immunosuppressive therapy.
      METHODS: Twenty-five active RA patients were randomized to treatment with either
      etanercept alone or in combination with methotrexate (MTX). The treatment
      response after 16 weeks was assessed using the European League Against Rheumatism
      (EULAR) response criteria. Blood samples were taken before the start of and every
      fourth week during the study. OPN, OPG, and total sRANKL were measured by enzyme
      linked immunosorbent assays (ELISAs) and hsCRP by highly sensitive turbidometry.
      RESULTS: At baseline, OPN and hsCRP were significantly (p<0.001) elevated
      compared to healthy persons. Compared to baseline only hsCRP levels decreased
      significantly (p<0.05 to p<0.001) in the EULAR responders through the study. OPN
      remained significantly (p<0.05) elevated at 16 weeks in patients with a low
      disease activity score (DAS< or =3.2). Total sRANKL increased significantly
      (p<0.05) from baseline to week 12. No statistically significant changes were
      observed in the non-responders. CONCLUSION: Active RA patients showed increased
      circulating levels of hsCRP and OPN, but only hsCRP decreased during etanercept
      therapy. Our findings suggest that OPN, OPG, total sRANKL, and hsCRP reflect
      different aspects of the inflammatory process in RA.

PMID- 18612925
TI  - Patients with rheumatoid arthritis report greater physical functional
      deterioration in lower limbs compared to upper limbs over 10 years.
AB  - OBJECTIVE: To examine the overall magnitude of change in self-reported physical
      function over a 10-year period in patients with rheumatoid arthritis (RA), and to
      compare changes in physical function between the lower and upper limbs. METHODS:
      Self-reported data on physical function were collected from the patients in the
      Oslo RA register (ORAR) through mail surveys between 1994 and 2004. The change in
      overall physical function was measured by the Short Form 36 (SF-36), the Modified
      Health Assessment Questionnaire (MHAQ), and the Arthritis Impact Measurement
      Scales (AIMS2). The MHAQ and AIMS2 were used to address activities related to
      lower and upper limb function. The magnitude of changes was expressed as crude
      and adjusted changes and standardized response means (SRMs). The analyses were
      adjusted for age, sex, duration of disease, and number of surgical procedures in
      the lower and upper limbs. RESULTS: A total of 414 patients [323 (78%) females,
      mean age 54.9 years and median disease duration 11.6 years] were included in
      these analyses. The overall physical function measured by AIMS2 physical and MHAQ
      deteriorated during 10 years. The magnitude of change in physical function was
      generally worse for activities related to lower limbs (SRM for adjusted changes
      0.16-0.27) than upper limbs (SRM 0.06-0.08). During the 10-year follow-up period,
      231 patients (56%) underwent orthopaedic surgery because of their RA. Findings
      were consistent after adjusting for surgical procedures. CONCLUSION: Patient
      reported lower limb function deteriorated more than upper limb function over a 10
      year period in patients with established RA.

PMID- 18612926
TI  - Adiponectin mitigates the severity of arthritis in mice with collagen-induced
      arthritis.
AB  - OBJECTIVE: Adiponectin (AD) is considered an inflammation modulator. In this
      study, we investigated the effect of AD on rheumatoid arthritis (RA) using a
      collagen-induced arthritis (CIA) mouse model and RA synovial fibroblasts (RASF).
      METHODS: Fifteen DBA/1 mice were divided into three groups. All mice, except the
      control group, were injected with type II collagen. AD was intra-articularly
      injected in the left hind legs after arthritis development (the AD-treated
      group). The severity of the arthritis was measured using an arthritis score and
      paw thickness. A histopathological assessment of joint sections was performed by
      haematoxylin/eosin (H&E) staining. Tumour necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta, IL-6, and matrix metalloproteinase (MMP)-3 expression was
      evaluated by immunohistochemical staining in the CIA mice. Synovial tissue was
      obtained from four RA patients during total joint replacement. RASF cultures were
      established from this tissue. RASF were pretreated with AD and stimulated by
      TNFalpha or IL-1beta. TNFalpha, IL-1beta, IL-6, and MMP-3 production was measured
      by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase
      chain reaction (RT-PCR). RASF proliferation was evaluated using the MTT assay.
      RESULTS: AD significantly mitigated the severity of the arthritis and
      histopathological findings indicative of RA in CIA mice. TNFalpha, IL-1beta, and
      MMP-3 expression decreased, but IL-6 expression in AD-treated joint tissues
      increased. Moreover, AD reduced TNFalpha, IL-1beta, and MMP-3 expression in
      stimulated RASF and increased IL-6 expression in IL-1beta-stimulated RASF. AD
      significantly inhibited IL-1beta-induced RASF proliferation, despite increased IL
      6 expression. CONCLUSION: These data suggest that AD may play an anti
      inflammatory role in the pathophysiology of RA.

PMID- 18612927
TI  - Reliability and validity of the Fatigue Severity Scale in Swedish for patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: The aim was to translate, test, and describe aspects of reliability
      and validity of the Fatigue Severity Scale (FSS) in Swedish (FSS-Swe) in patients
      with systemic lupus erythematosus (SLE). METHODS: Patients with stable SLE, low
      or moderate disease activity, and low organ damage were included. Forward and
      back translations of the FSS were performed. Construct validity was tested with
      32 women using a first Swedish translation. Feasibility, ceiling and floor
      effects, internal consistency, test-retest reliability, and content validity were
      tested on a slightly modified final version of the FSS-Swe in a non-selected
      group of patients (n = 23). RESULTS: There were correlations (p< or =0.05)
      between the FSS-Swe and overall disease activity according to the Systemic Lupus
      Activity Measure (SLAM) (r(s) = 0.48) and the SLAM Visual Analogue Scale (SLAM
      VAS) (r(s) = 0.46); between the FSS-Swe and eight subscales of the Swedish 36
      Item Medical Outcomes Study Short-Form Health Survey (SF-36) (r(s) = -0.41 to 
      0.65) and between the FSS-Swe and age (r(s) = -0.35). All patients answered all
      FSS-Swe questions at both test and retest. There was one ceiling effect in one
      question on one occasion. The Kolmogorov-Smirnov test indicated normal
      distribution. Cronbach's alpha was 0.94 and corrected item-to-total correlation
      exceeded 0.3. There were no significant systematic test-retest differences, and
      the median-weighted kappa coefficient was 0.75. Twenty patients understood the
      questions in FSS-Swe, 18 considered they were relevant, reflected their fatigue,
      and that none should be excluded. Five items were suggested to be included.
      CONCLUSIONS: The FSS-Swe supports construct validity, is feasible, has no
      important ceiling or floor effects, has satisfactory internal consistency,
      substantial test-retest reliability, and satisfactory content validity in the SLE
      patients studied. However, its sensitivity to change needs to be tested.

PMID- 18612928
TI  - The presence of anti-centromere antibodies may predict progression of estimated
      pulmonary arterial systolic pressure in systemic sclerosis.
AB  - OBJECTIVE: To define the risk factors associated with a relatively rapid increase
      in estimated pulmonary arterial systolic pressure (PASP) in patients with
      systemic sclerosis (SSc). METHODS: SSc patients undergoing screening for
      pulmonary arterial hypertension (PAH) by echocardiography were identified and
      their charts were retrospectively reviewed. In all patients, we recorded PASP,
      pulmonary function, and clinical and laboratory data. PAH was defined as an
      estimated PASP> or =40 mmHg. In each patient, the PASP values with their
      corresponding time intervals were fitted to a linear function and the slope of
      the line was calculated. RESULTS: Seventy-one patients with at least two
      echocardiographic studies each were analysed. In 16 (23%) patients, the rate of
      PASP progression was > or =2.5 mmHg/year whereas in the remaining 55 (77%)
      patients the rate of progression was <2.5 mmHg/year. In multiple logistic
      regression analysis, anti-centromere antibodies (ACA) (OR 8.75, CI 1.12-68.38, p
      = 0.039) and age > or =50 years at diagnosis (OR 8.76, CI 1.28-60.14, p = 0.027)
      were independently associated with a rise of PASP by > or =2.5 mmHg/year.
      Baseline forced vital capacity (FVC) <70% (predicted), Raynaud's duration
      preceding skin manifestations by > or =5 years, and fibrosis on lung computed
      tomography (CT) were not associated with a rapid rise of PASP (p>0.05).
      CONCLUSIONS: Old age at diagnosis and ACA are associated with a relatively rapid
      rise of PASP estimated by echocardiography in SSc. Screening for PAH in these
      patients may, if followed by right heart catheterization, detect PAH at an
      earlier stage and guide therapeutic decisions.

PMID- 18612929
TI  - Fatigue and blood pressure in primary Sjogren's syndrome.
AB  - OBJECTIVE: Primary Sjogren's syndrome (SS) is an autoimmune disease characterized
      by fatigue. Little is known about the genesis of fatigue. Fatigue is thought to
      represent a multidimensional concept and it is important to be able to measure it
      confidently. The aims were to evaluate the reliability and validity of the 20
      item Multidimensional Fatigue Inventory (MFI-20) in SS and to search for factors
      associated with this disabling symptom. METHODS: Forty-eight women with primary
      SS completed the MFI-20 questionnaire. The results were compared with age-matched
      women with fibromyalgia (FM) and healthy controls. Convergent construct validity
      was assessed by correlations to a Visual Analogue Scale (VAS) for global fatigue
      by Spearman's correlation (r(s)). Test-retest reliability was analysed by the
      intraclass correlation coefficient (ICC) in 28 women. Associations between
      clinical variables and subscales of the MFI-20 were analysed. RESULTS: The SS
      women scored significantly higher in all subscales of the MFI-20 compared to
      controls but similar to FM. The ICCs were satisfactory, ranging from 0.66 for
      general fatigue to 0.85 for the total score of MFI-20. All subscales correlated
      significantly to VAS for global fatigue, general fatigue showing the highest
      correlation (r(s) = 0.70). The estimated number of hours of sleep/day was
      significantly associated with many of the fatigue dimensions. All five subscales
      of the MFI-20 were inversely associated with diastolic blood pressure (BP) and
      two with systolic BP. CONCLUSIONS: The MFI-20 was found to be a reliable and
      valid tool for the measurement of fatigue in primary SS. High levels of fatigue
      were correlated with low BP, suggesting an associated involvement of the
      autonomic nervous system.

PMID- 18612930
TI  - The role of interleukin-10 promoter polymorphisms in primary Sjogren's syndrome.
AB  - OBJECTIVE: To determine the impact of a broad spectrum of different polymorphisms
      within the interleukin-10 (IL-10) promoter gene on disease susceptibility to
      primary Sjogren's syndrome (pSS), clinical manifestations, and autoantibody
      production. METHODS: We genotyped 111 unrelated German Caucasian patients with
      pSS and 145 healthy controls for the single nucleotide polymorphisms (SNPs) at
      positions -2849, -2776, -2769, -2763, -1349, -1082, -851, -819, -657, and -592
      and for the microsatellites IL10.R and IL10.G. Allele and haplotype distributions
      were compared between patients and controls and between subgroups of patients
      with different clinical and laboratory findings. RESULTS: We found no significant
      differences in the allele or haplotype frequencies between pSS patients and
      healthy controls. After Bonferroni correction we found a significant association
      of the ACC haplotype (at the -1082, -819, and -592 loci) with immunoglobulin
      (Ig)A antibodies to anti-alpha-fodrin. CONCLUSION: Overall we found no
      associations of IL-10 promoter polymorphisms with the susceptibility to pSS in
      our cohort. The finding that the production of IgA anti-alpha-fodrin antibodies
      is associated with polymorphisms within the IL-10 promoter region suggests a
      genetic contribution to the generation of these antibodies.

PMID- 18612931
TI  - Primary Sjogren's syndrome in men.
AB  - OBJECTIVE: To determine whether there were any clinical and biological
      differences between male and female patients with primary Sjogren's syndrome
      (pSS) in a large bicentric series of patient. METHODS: We studied 419 consecutive
      patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS
      according to American-European criteria, attending two different Departments of
      Internal Medicine in France. The 42 (9%) male patients in this cohort comprised
      the male group described in this study. RESULTS: Extraglandular manifestations
      during the course of the disease were present in 37 (89%) of our male patients
      with pSS. The extraglandular manifestations were similar among the two groups
      except that the male patients showed a lower frequency of depression or asthaenia
      (5% vs. 20%, p = 0.014) compared with the females. A significantly greater
      percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia
      (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male
      patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common
      in the male patients, but with no statistical significance (10% vs. 3%, p =
      0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04).
      CONCLUSION: Although pSS is typically a disease affecting women, clinicians
      should be aware that it may be diagnosed in male patients. Except for
      haematological presentation, we could not find any notable differences in
      clinical and immunological characteristics between male and female patients with
      pSS.

PMID- 18612932
TI  - Neurological and pulmonary adverse effects of subcutaneous methotrexate therapy.
AB  - We report the case of a patient receiving subcutaneous methotrexate (MTX)
      treatment for rheumatoid arthritis (RA) who developed a complex pattern of
      neurological and pulmonary symptoms. Fluctuant dysarthria, magnetic gait,
      weakness and dysmetria of the lower limbs, as well as symptoms and signs
      consistent with a diagnosis of pneumonitis started within 6 weeks of initiating
      MTX treatment and slowly resolved after its discontinuation. This case highlights
      the fact that even the relatively low doses of MTX in the therapy of RA can
      produce neurotoxicity, which can become manifest in a broad range of symptoms.

PMID- 18612933
TI  - Pneumococcal sacroiliitis in a 4-year-old boy.
AB  - Pyogenic sacroiliitis is an extremely rare manifestation of invasive pneumococcal
      disease in childhood as only four cases have been described to date. We report
      and comment on a case of pneumococcal sacroiliitis in a 4-year-old boy. This
      patient was diagnosed promptly on account of the symptom triad of fever, buttock
      pain, and limping gait, along with characteristic findings in magnetic resonance
      imaging (MRI) and bone scans, and recovered fully after 6 weeks of antimicrobial
      therapy. Pyogenic sacroiliitis is an uncommon disease in which the diagnosis is
      often delayed because of nonspecific clinical presentation. The key to successful
      management is early diagnosis in which MRI and bone scan findings play a crucial
      role. If the diagnosis is established promptly, most patients can be managed
      successfully following the therapeutic principles used in other osteoarticular
      infections.

PMID- 18612934
TI  - Membranous glomerulopathy associated with rheumatoid arthritis may respond to
      rituximab.

PMID- 18612935
TI  - Gastric antral vascular ectasia (GAVE) associated with systemic sclerosis.

PMID- 18612936
TI  - Doppler ultrasonography to diagnose temporal arteritis in the setting of a large
      community hospital.

PMID- 18612937
TI  - Rheumatoid arthritis, Poncet's disease, or spondyloarthropathy.

PMID- 18612939
TI  - [Do people with mental disorders who, due to complete reduction in earning
      capacity, receive a temporary pension want to return into active employment?].
AB  - In Germany the number of invalidity pensions due to mental disorders is
      increasing. More than one third of these insurants do not take part in
      rehabilitation measures before their early retirement. Only 6 % return into their
      employment relationship. HYPOTHESES: 1. People with mental disorders still have
      severe health problems after their two-year temporary leave/retirement. 2. About
      one third of these insurants are generally interested in being reintegrated into
      their jobs. 3. Their motivation for reintegration depends on their age and their
      individual health status. METHOD: Data of all insurants (of DRV Braunschweig
      Hannover) under 50 who drew a short-term benefit due to complete reduction in
      earning capacity in 2004 (n = 352) were collected with the help of an anonymous
      questionnaire (response rate = 54 %). This questionnaire compiled data on their
      general health status, their functional capacity and work ability, their
      motivation for returning to work as well as psychosocial aspects. At the same
      time, socio-demographic characteristics from the regional pension insurance
      database were analyzed. RESULTS: Compared to patients treated in hospitals, those
      insurants who had been on a two-year temporary leave were psychologically
      strongly distressed. There was also a gender effect: Women in particular showed
      significant limitations in daily activities/routines, a higher level of anxiety
      and somatization. Less than 30 % of the pensioners were motivated for vocational
      rehabilitation in order to return to their jobs. The motivation was not dependant
      on the psychological load and the age but most probably on the somatization
      tendencies and the daily activities. DISCUSSION: It seems that classic vocational
      rehabilitation for insurants who already receive a disability pension does not
      lead to a higher rate of reintegration into work. The relatively large number of
      insurants who want to return to their jobs implies the necessity of a special
      rehabilitation programme with concepts for reintegration: an individual case
      management should help to continually counsel the patients and, by means of work
      trial phases, prepare them for their return into their career.

PMID- 18612940
TI  - [Parenthood and parenting stress: psychometric testing of the Parenting Stress
      Index (PSI) in a German sample].
AB  - The Parenting Stress Index (PSI) consists of 120 items measuring the subjective
      burden--labelled as parenting stress--of adults in parenting children from the
      age of newborns up to 12 years. The PSI is a self report scale which was
      developed in the US in 1976. Since then the PSI has been widely used in family
      and parenting research and was validated in many different languages but not yet
      in German. Therefore we administered the PSI to a sample of 372 German speaking
      parents with children from newborns up to 12 years of age in Basel, Switzerland.
      The questionnaire was handed out to parents in schools, kindergartens and day
      care centers along with one other complementary questionnaire such as the Beck
      Depression Inventory (BDI) or the Dyadic Adjustment Scale (DAS) measuring similar
      or divergent constructs. Internal consistency was high with a Cronbach's alpha
      Coefficient of 0.95 for total stress and 0.91 and 0.92 for the subscores of the
      child domain and parent domain respectively. The selectivity of most items ranged
      from sufficient to good. In order to assess the structure of the PSI factor
      analysis was performed. The principle component analysis revealed a two-factor
      solution accounting for 58 % of variance. The factorial structure of the original
      scale was therefore replicated. However, a three-factor solution seemed to
      describe data better. Correlations with other self report scales resulted as
      predicted. In summary the German translation of the PSI proved to assess reliably
      the construct of parenting stress. This instrument will serve family researchers
      and clinicians in German speaking countries to detect families at risk.

PMID- 18612941
TI  - Chrysin induces hyperalgesia via the GABAA receptor in mice.
AB  - Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in many plants
      including PASSIFLORA COERULEA L. Researchers have performed extensive and
      detailed investigations on the behavioral and pharmacological effects of chrysin
      IN VIVO, but there was little information available on the effect of chrysin on
      nociception. Therefore, the present study was undertaken to investigate the
      effect of chrysin on the nociceptive threshold using the tail-immersion test.
      Intraperitoneal ( I. P.) injection of chrysin (10, 25, 50, 75, 100 mg/kg) dose-
      and time-dependently induced a pronounced decrease of the tail withdrawal
      latencies (TWL), thus characterizing a hyperalgesic effect (ED50 = 65.59 mg/kg).
      The following results showed that GABAA receptors were involved in the
      hyperalgesic effects of chrysin. 1) The hyperalgesia induced by chrysin was
      significantly and dose-dependently blocked by pretreatment with flumazenil (0.75,
      1 mg/kg, I. P.), a specific antagonist for benzodiazepine sites associated with
      GABAA receptors. 2) Bicuculline (2, 4 mg/kg, I. P.), a GABAA receptor antagonist,
      markedly antagonized the hyperalgesic effect of chrysin in a dose-dependent
      manner. 3) Picrotoxin (2 mg/kg, I. P.), a chloride channel blocker, could also
      notably antagonize the hyperalgesia of chrysin. Oral administration of chrysin
      (75 mg/kg) also produced a hyperalgesic effect in the tail-immersion test. In
      addition, diazepam (1 mg/kg, I. P.) showed a marked antinociceptive effect, which
      was completely blocked by flumazenil (1 mg/kg, I. P.). In conclusion, it can be
      summarized that both I. P. and oral administration of chrysin produced a
      significant hyperalgesic effect in the tail-immersion test and that the
      hyperalgesic effect of chrysin may be associated with GABAA receptors.

PMID- 18612942
TI  - In vitro metabolic stability and intestinal transport of P57AS3 (P57) from Hoodia
      gordonii and its interaction with drug metabolizing enzymes.
AB  - Hoodia gordonii, a succulent cactus-like plant growing in South Africa, has been
      used in traditional medicine for its appetite suppressant properties. Its use as
      a dietary supplement to promote weight loss has recently gained popularity. An
      oxypregnane steroidal glycoside P57AS3 (P57) is reported to be the active
      constituent of the sap extract responsible for anorexigenic activity. No
      information is available about its metabolic stability, intestinal transport and
      interaction with drug metabolizing enzymes. In the present investigation, the
      metabolic stability of P57 in human liver microsomes and its interaction with
      drug metabolizing enzymes (CYP1A2, 2C9, 3A4 and 2D6) were determined. Intestinal
      transport of P57 was studied in the Caco-2 cell model of intestinal transport and
      absorption. P57 was metabolically stable in the presence of human liver
      microsomes. The compound inhibited CYP3A4 activity with an IC50 value of 45
      microM, whereas the activity of CYP 1A2, 2C9 and 2D6 was not inhibited. In the
      Caco-2 model, P57 exhibited a higher transport in the secretory direction than in
      the absorptive direction with efflux ratios of 3.1 and 3.8 at 100 and 200 microM,
      respectively. The efflux was inhibited by selective inhibitors of multidrug
      resistance associated proteins MRP1/MRP2 (MK-571) and P-gp (verapamil). In
      conclusion, intestinal transport of P57 was mediated by P-gp and MRP
      transporters. The compound was metabolically stable and showed weak inhibition of
      CYP 3A4.

PMID- 18612943
TI  - Phenols from the roots of Rheum palmatum attenuate chemotaxis in rat hepatic
      stellate cells.
AB  - In liver injury, hepatic stellate cells (HSCs) acquire an activated phenotype,
      migrate to the injured region in response to chemotactic factors and produce
      extracellular matrix (ECM) proteins including alpha-smooth muscle actin (alpha
      SMA) and collagen in order to repair the damage. HSC-T6, a cell line of rat HSCs,
      was used in in vitro experiments. TGF-beta1 was used as a chemoattractant. The
      expression of alpha-SMA was used as a marker of activated hepatic stellate cells
      and cell migration was assayed with the Transwell method to investigate the
      active principles of the roots of Rheum palmatum L. (Dahuang), a well-known
      traditional Chinese herb used for treating liver diseases. Under cell activation
      and chemotaxis-directed fractionation and purification, four anthraquinones,
      rhein ( 1), emodin ( 2), chrysophanol ( 3) and physcion ( 4), and four
      phenylbutanoids, lindleyin ( 5), isolindleyin ( 7), 4-(4'-hydroxyphenyl)-2
      butanone 4'- O-beta- D-glucopyranoside ( 8), and 4-(4'-hydroxyphenyl)-2-butanone
      ( 9), and a stilbene, 3,5,4'-trihydroxystilbene 4'- O-beta- D-glucopyranoside 6'-
      O-gallate ( 6) were isolated from the active fractions. Among them, compounds 1
      and 2 inhibited alpha-SMA expression. However, compounds 3, 4, 6 and 8 attenuated
      chemotactic migration, but not alpha-SMA expression.

PMID- 18612944
TI  - Metabolic profiling of the Mexican anxiolytic and sedative plant Galphimia glauca
      using nuclear magnetic resonance spectroscopy and multivariate data analysis.
AB  - Galphimia glauca is popularly employed in Mexico for the treatment of central
      nervous system disorders. Pharmacological and phytochemical studies have resulted
      in the identification of the anxiolytic and sedative principle consisting of a
      mixture of nor-secofriedelanes, named the galphimine series (1 - 9). These active
      constituents were found in plants collected in the vicinity of a restricted
      region in Central Mexico, where this species is abundant. A metabolic profiling
      carried out by means of 1H-NMR spectroscopy and multivariate data analysis was
      applied to crude extracts from wild plant populations, collected from six
      different locations as a quality control assessment, in order to differentiate
      their chemical profile. Principal component analysis (PCA) of the 1H-NMR spectra
      revealed clear variations among the populations, with two populations out of the
      six studied manifesting differences, when the principal components PC-1 and PC-2
      were analyzed. These two PCs permitted the differentiation of the various sample
      populations, depending on the presence of galphimines. This information
      consistently correlated with the corresponding HPLC analysis. The
      neuropharmacological effects of the crude extracts were evaluated by using ICR
      mice in the elevated plus maze, as well as the sodium pentobarbital-induced
      hypnosis models. Both assays demonstrated anxiolytic and sedative responses only
      among those sample populations which had previously been differentiated by PC-1.
      Partial least square regression-discriminant analysis (PLS-DA) also confirmed a
      strong correlation between the observed effects and the metabolic profiles of the
      plants. The overall results of this study confirm the benefits of using metabolic
      profiling for the in silico analysis of active principles in medicinal plants.

PMID- 18612945
TI  - Potential of spice-derived phytochemicals for cancer prevention.
AB  - Although spices have been used for thousands of years and are known for their
      flavor, taste and color in the food, they are not usually recognized for their
      medicinal value. Extensive research within the last two decades from our
      laboratory and others has indicated that there are phytochemicals present in
      spices that may prevent various chronic illnesses including cancerous, diabetic,
      cardiovascular, pulmonary, neurological and autoimmune diseases. For instance,
      the potential of turmeric (curcumin), red chilli (capsaicin), cloves (eugenol),
      ginger (zerumbone), fennel (anethole), kokum (gambogic acid), fenugreek
      (diosgenin), and black cumin (thymoquinone) in cancer prevention has been
      established. Additionally, the mechanism by which these agents mediate anticancer
      effects is also becoming increasingly evident. The current review describes the
      active components of some of the major spices, their mechanisms of action and
      their potential in cancer prevention.

PMID- 18612946
TI  - In vitro comparison and evaluation of seven gastric closure modalities for
      natural orifice transluminal endoscopic surgery (NOTES).
AB  - BACKGROUND AND STUDY AIMS: Secure transluminal closure is the most fundamental
      prerequisite for the safe introduction of natural orifice transluminal endoscopic
      surgery (NOTES). The aim was to compare acute strength of various gastrotomy
      closure techniques in an in vitro porcine stomach model by assessing leak
      pressures. METHODS: Standardized gastrotomies were closed manually, without the
      use of an endoscope, by one of seven NOTES closure devices: (i) T tags, (ii)
      purse string modified T tags, (iii) Eagle Claw VIII, (iv) Resolution clips, (v)
      flexible stapler; (vi) purse string suturing device, and (vii) flexible
      Endostitch. After closure, each specimen was fixed on the experimental apparatus
      and the pressure was gradually increased. By linking the pressure gauge and two
      cameras, the leak location and pressure could be determined in detail. We began
      by collecting gold standard reference values, by testing 15 gastrotomies closed
      with interrupted surgical sutures; these were associated with a mean leak
      pressure of 206 mmHg (SD 59). Using a noninferiority design, a sample size of 11
      specimens for each NOTES closure technique was determined. RESULTS: The
      Resolution clips ( P = 0.0285), Eagle Claw VIII ( P = 0.0325), flexible stapler (
      P < 0.001) and flexible Endostitch ( P = 0.002) produced noninferior closures in
      comparison with the predetermined gold standard; T tags ( P > 0.6775), purse
      string modified T tags ( P > 0.999), and the purse string suturing device ( P =
      0.9875) resulted in inferior closures. CONCLUSIONS: The Eagle Claw VIII,
      Resolution clips, flexible stapler and flexible Endostitch produced noninferior
      closures in comparison with surgical closure in this model. These techniques seem
      to be the prime candidates for further testing in animal experiments before human
      trials can be initiated.

PMID- 18612947
TI  - EUS and clinical characteristics of cystic pancreatic neuroendocrine tumors.
AB  - Pancreatic neuroendocrine tumors (PNETs) may rarely appear as cystic or mixed
      solid-cystic masses. The endoscopic ultrasound (EUS) morphology and cyst fluid
      characteristics of these tumors are not well clarified. We retrospectively
      identified nine adult patients with nine single cystic pancreatic neuroendocrine
      tumors (CNETs). These nine included 0.67 % of the 1344 patients with pancreatic
      cystic lesions and 9.5 % of the 95 confirmed PNETs evaluated over the 12-year
      study period. At presentation, four patients were asymptomatic and five had known
      acute pancreatitis (n = 2), MEN-1 syndrome with hypoglycemia (n = 1), and
      abdominal pain (n = 2). Median maximal tumor diameter was 26 mm (range 20 - 64
      mm). EUS morphology was mixed solid and cystic (n = 4) or cystic alone (n = 5).
      Cytology from EUS-fine-needle aspiration (FNA) (median 2 passes; range 1 - 6)
      demonstrated a PNET, and immunocytochemistry was confirmatory in all patients.
      Cyst fluid carcinoembryonic antigen (CEA) (n = 4) and amylase (n = 5) ranged from
      0.1 to 1.8 ng/ml (normal 0 - 2.5 ng/ml) and 72 to 1838 U/L (normal 25 - 161 U/L),
      respectively. Six patients underwent surgery, and the preoperative diagnosis was
      confirmed in all.

PMID- 18612948
TI  - European Society of Gastrointestinal Endoscopy (ESGE) Guidelines: flexible
      enteroscopy for diagnosis and treatment of small-bowel diseases.

PMID- 18612949
TI  - [49th Congress of the German Society for Pneumology and Respiratory Medicine, 9.
      12.4. 2008 in Lubeck].

PMID- 18612950
TI  - Prospective blinded comparison of surface versus wire electromyographic analysis
      of muscle recruitment in shoulder instability.
AB  - BACKGROUND: This pilot study assesses level of agreement between surface and fine
      wire electromyography (EMG), in order to establish if surface is as reliable as
      fine wire in the diagnosis and treatment of abnormal muscle patterning in the
      shoulder. METHOD: Eighteen participants (11 female) with unstable shoulders were
      recruited after written consent and ethical approval. Anthropometric information
      and mean skinfold size for triceps, subscapular, biceps and suprailiac sites were
      obtained. Triple-stud self-adhesive surface electrodes ('Triode'; Thermo
      Scientific, Physio Med Services, Glossop, Derbyshire, England) were placed over
      pectoralis major (PM), latissimus dorsi (LD), anterior deltoid (AD) and
      infraspinatus (IS) at standardized locations. Participants performed five
      identical uniplanar standard movements (flexion, abduction, external rotation,
      extension and cross-body adduction). After a 20-minute rest period, a dual-needle
      technique for fine-wire insertion was performed and the standard movements were
      repeated. An experienced examiner in each technique reported if muscle activation
      patterns differed from agreed normal during any movement and were blinded to the
      other test results. Sensitivity, specificity and Kappa values for level of
      agreement between methods were calculated for each muscle according to the method
      of Altman (1991). RESULTS: Fifteen participants were successfully tested.
      Sensitivity, specificity and Kappa values between techniques for each muscle were
      PM (57%, 50%, 0.07), LD (38%, 85%, 0.22), AD (0%, 76%, -0.19) and IS (85%, 75%,
      0.6). Only IS demonstrated high sensitivity and specificity and a moderate level
      of agreement between the two techniques. There was no correlation between
      skinfold size and agreement levels. CONCLUSION: The use of surface EMG may help
      to classify types of shoulder instability and recognize abnormal muscle patterns.
      It may allow physiotherapists to direct specific rehabilitation strategies,
      avoiding strengthening of inappropriate muscles. It has a reasonable degree of
      confidence to evaluate IS but may have poor sensitivity in detecting abnormal
      patterns in PM, LD and AD. Further work is required to see if investigator
      interpretation may have been a factor for the poor level of agreement.

PMID- 18612951
TI  - Prenatal diagnosis of a jumping translocation.

PMID- 18612953
TI  - Optimization of 2,3-butanediol production by Klebsiella oxytoca through oxygen
      transfer rate control.
AB  - Production of 2,3-butanediol by Klebsiella oxytoca is influenced by the degree of
      oxygen limitation. During batch culture studies, two phases of growth are
      observed: energy-coupled growth, during which cell growth and oxygen supply are
      coupled; and, energy-uncoupled growth, which arises when the degree of oxygen
      limitation reaches a critical value. Optimal 2,3-butanediol productivity occurs
      during the energy-coupled growth phase. In this article, a control system which
      maintains the batch culture at a constant level of oxygen limitation in the
      energy-coupled growth regime has been designed. Control, which involves feedback
      control on the oxygen transfer coefficient, is achieved by continually increasing
      the partial pressure of oxygen in the feed gas, which in turn continually
      increases the oxygen transfer rate. Control has resulted in a balanced state of
      growth, a repression of ethanol formation, and an increase in 2,3-butanediol
      productivity of 18%.

PMID- 18612954
TI  - An energetic model for oxygen-limited metabolism.
AB  - Microbial production of 2,3-butanediol by Klebsiella oxytoca occurs under
      conditions of an oxygen limitation. The extent to which substrate is oxidized to
      2,3-butanediol and its coproducts, (acetic acid, acetoin, and ethanol) and the
      relative flow rates of substrate to energetic and biosynthetic pathways are
      controlled by the degree of oxygen limitation. Two energetic relationships which
      describe the response to an oxygen limitation have been derived. The first
      relationship describes the coupling between growth and energy production observed
      under oxygen-limited conditions. This allows calculation of energetic parameters
      and modeling of the cell mass and substrate profiles in terms of the degree of
      oxygen limitation only. The second relationship describes the average degree of
      oxidation and the rate of the end-product flow. The model has been tested with
      both batch and continuous culture. During these kinetic studies, two phases of
      growth have been observed: energy-coupled growth, which was described above; and,
      energy-uncoupled growth, which arises when the degree of oxygen limitation
      reaches a critical value. Optimal culture performance with respect to 2,3
      butanediol productivity occurs during energy-coupled growth.

PMID- 18612955
TI  - Growth rate effects on fundamental transport properties of bacterial populations.
AB  - In many natural environments, bacterial populations experience suboptimal growth
      due to the competition with other microorganisms for limited resources. The
      chemotactic response provides a mechanism by which bacterial populations can
      improve their situation by migrating toward more favorable growth conditions. For
      bacteria cultured under suboptimal growth conditions, evidence for an enhanced
      chemotactic response has been observed previously. In this article, for the first
      time, we have quantitatively characterized this behavior in terms of two
      macroscopic transport coefficients, the random motility and chemotactic
      sensitivity coefficients, measured in the stopped-flow diffusion chamber assay.
      Escherichia coli cultured over a range of growth rates in a chemostat exhibits a
      dramatic increase in the chemotactic sensitivity coefficient for D-fucose at low
      growth rates, while the random motility coefficient remains relatively constant
      by comparison. The change in the chemotactic sensitivity coefficient is accounted
      for by an independently measured increase in the number of galactose-binding
      proteins which mediate the chemotactic signal. This result is consistent with the
      relationship between macroscopic and microscopic parameters for chemotaxis, which
      was proposed in the mathematical model of Rivero and co-workers.

PMID- 18612956
TI  - On-line monitoring of monoclonal antibodies in animal cell culture using a
      grating coupler.
AB  - A grating coupler was used for the on-line determination of monoclonal antibodies
      produced in perfused animal cell bioreactor. The device was connected with the
      culture vessel via a flow-injection analysis (FIA) system, which was controlled
      automatically. Specific antimouse lgG antibodies were immobilized on the surface
      of the sensor-chip. After injection of the sample, the binding of mouse lgG was
      observed in real time. The regeneration of the binding sites of the immobilized
      antibodies using an acidic solution allowed the on-line detection of produced
      monoclonal antibodies in the range of 10 to 150 microg/mL. In contrast to other
      techniques coupled to bioprocesses, the developed method represents a regenerable
      direct immunosensor. Results were compared with standard ELISA techniques (off
      line) and a competitive immunochemical assay using the grating coupler (off
      line).

PMID- 18612957
TI  - Transfer vectors for maximal expression of passenger genes in the Bombyx mori
      nuclear polyhedrosis virus expression system.
AB  - A series of Bombyx mori nuclear polyhedrosis virus (Bm-NPV) transfer vectors has
      been developed containing various lengths of the polyhedrin promoter, including
      sequences 3' of the initiation codon. The ATG initiation codon was mutated in
      some of these vectors to allow for the production of authentic nonfusion
      proteins. The ability of the various polyhedrin promoter constructs to direct
      expression of foreign gene sequences was assessed using two test genes,
      chloramphenicol acetyl transferase (cat), and human metallothionein II.
      Accumulation of cat mRNA and nonfused protein was low when only polyhedrin
      promoter sequences to -8 (relative to the translational start site of polyhedrin
      mRNA) were included in the transfer vector, but cat expression was comparable
      with that of the wild-type polyhedrin gene when promoter sequences to +5 were
      present. Further addition of polyhedrin gene sequences to +26 or +94 resulted in
      no further increase in expression. Similar results were obtained for expression
      of human metallothionein II, where constructs encoding polyhedrin-metallothionein
      fusion proteins containing polyhedrin sequences to at least +5 resulted in high
      levels of mRNA and protein accumulation. The expression vectors containing the
      +5, +26, or +94 BmNPV polyhedrin promoter can thus be used to direct maximal
      levels of production of nonfused proteins (when the polyedrin ATG has been
      mutated) or of fusion proteins, depending on which is more suitable for a
      particular application. These new vectors are a useful addition to those
      presently available and should increase the utility of the BmNPV expression
      system for large-scale protein production.

PMID- 18612958
TI  - Multigradient method for optimization of slow biotechnological processes.
AB  - A new method (named a "jumping spider") is introduced for the optimization of
      slow biotechnological processes. The more traditional sequential experimentation
      (i.e., gradient search, simplex, etc.) is not well suited for slow dynamic
      processes, e.g., plant cell culture and differentiation. Therefore, a more
      simultaneous approach is proposed. A large number of initial experiments are
      performed, on the basis of which several of the initial experiments are selected
      as starting points. A search is then performed simultaneously from several
      gradient directions and the optimum is estimated by a quadratic approximation. In
      simulations, the spider generally climbs up the slopes quickly and the final
      estimator yields good maximum point estimates even on a complex topography. The
      spider may even approach more than one local maximum point simultaneously. As a
      model application, the average xylitol conversion rate of Candida guilliermondii
      was optimized in relation to cultivation volume (oxygen availability) and the
      concentration of nitrogen and phosphorus in the medium. A threefold increase in
      xylitol production was obtained with three experimental steps.

PMID- 18612959
TI  - On the applicability of adaptive bioprocess state estimators.
AB  - This article presents an industrial case study, examining the application of a
      novel adaptive biomass estimator to an industrial microfungi production process.
      It is our intention that this contribution should focus upon the implementation
      issues of the algorithm, in preference to a rigorous theoretical development. The
      novel algorithm adopted is developed from Adaptive Inferential Estimation studies
      of Guilandoust and co-workers. The technique utilizes input-output process
      measurements obtained at different frequencies, thereby providing more frequent
      estimates of biomass concentration than are otherwise available from off-line
      laboratory analyses. The algorithm is particularly suited to the biotechnology
      industry, as it is capable of utilizing irregular assay measurements with varying
      delays.Although this article demonstrates the encouraging industrial implications
      of the adaptive algorithm, like all adaptive techniques currently developed, it
      is restricted by the inability to perform robust on-line system identification.
      The ultimate selection of a "suboptimal" "fixed parameter" algorithm for on-line
      implementation, is therefore directly attributable to these inadequacies. Aspects
      of data acquisition, data pretreatment, and data quality are critical for real
      process applications, and while some practical approaches are adopted here, many
      important implementation problems remain unresolved.

PMID- 18612960
TI  - Growth and production modeling in hybridoma continuous cultures.
AB  - Several experimental data on continuous cultures of hybridoma cells show that
      monoclonal antibody productivity is a decreasing function of dilution rate. It
      has been suggested that this unusual behavior may be due to the arrest of a
      fraction of cycling cells at a critical point of Phase G(1). Although this
      hypothesis has been recently investigated by using population balance models,
      mathematical analysis has been performed without accounting for the dynamics of
      the arrested cells properly. In this article, a more general and accurate
      approach is presented and new specific assumptions are introduced to characterize
      the arrest and the later progress through the cycle. Two different models
      (stochastic and deterministic) and two different critical points for the arrest
      (at the beginning and at the end of G(1)) are considered. The cell cycle
      parameters are estimated so that data predicted by the model fit those reported
      in the literature. In particular, the fraction of arrested cells, the cell arrest
      probability, and the mean cell generation time are computed as functions of the
      dilution rate. Results so far obtained predict that there is an optimal value of
      dilution rate for maximizing specific production rate of monoclonal antibody.

PMID- 18612961
TI  - Rapid purification of DesPro(2)-Val15-Leu17-aprotinin from the culture broth of a
      recombinant Saccharomyces cerevisiae.
AB  - A rapid two-step procedure has been developed for the purification of Despro(2)
      Val15-Leu17-aprotinin from the culture supernatant of a recombinant yeast by
      affinity and ion-exchange chromatography. DesPro(2)-Val15-Leu17-aprotinin was
      purified to homogeneity, as demonstrated by dodecylsulfate gel electrophoresis
      and analysis of the N-terminal amino acid sequence.

PMID- 18612962
TI  - Use of ATP to characterize biomass viability in freely suspended and immobilized
      cell bioreactors.
AB  - This work describes investigations into the viability of cells growing on 3,4
      dichloroaniline (34DCA). Two bioreactors are employed for microbial growth, a
      continuous stirred tank (CST) bioreactor with a 2-L working volume, and a three
      phase air lift (TPAL) bioreactor with a 3-L working volume. Experiments have been
      performed at several dilution rates between 0.027 and 0.115 h(-1) in the CST
      bioreactor and between 0.111 and 0.500 h(-1) in the TPAL bioreactor. The specific
      ATP concentration was calculated at each dilution rate in the suspended biomass
      in both bioreactors as well as in the immobilized biomass in the TPAL bioreactor.
      The ATP was extracted from the cells using boiling tris-EDTA buffer (pH 7.75),
      and the quantity determined using a firefly (bioluminescence) technique. The
      cultures were inspected under an electron microscope to monitor compositional
      changes. Results from the CST bioreactor showed that the biomass-specific ATP
      concentration increases from 0.44 to 1.86 mg ATP g(-1) dry weight (dw) as
      dilution rate increases from 0.027 to 0.115 h(-1). At this upper dilution rate
      the cells were washed out. The specific ATP concentration reached a limiting
      average value of 1.73 mg ATP g(-1) dw, which is assumed to be the quantity of ATP
      in 100% viable biomass. In the TPAL bioreactor, the ATP level increased with
      dilution rate in both the immobilized and suspended biomass. The specific ATP
      concentration in the immobilized biomass increased from approximately 0.051 mg
      ATP g(-1) dw at dilution rates between 0.111 and 0.200 h(-1) to approximately
      0.119 mg ATP g(-1) dw at dilution rates between 0.300 and 0.500 h(-1). This
      indicates that the immobilized biomass contained a viable cell fraction of around
      5%. Based on these results, kinetic data for freely suspended cells should not be
      applied to the modeling of immobilized cell systems on the assumption that
      immobilized biomass is 100% viable.

PMID- 18612963
TI  - Morphological characterization of yeast by image analysis.
AB  - A semiautomatic image analysis method, with minimal operator intervention, has
      been developed to characterize the morphology of yeast cells under the assumption
      that they have an ellipsoidic shape. The cells are observed by optical microscopy
      and the surface and the minor and major half-axes of the projection of the
      ellipsoid on the image plane are determined. Using this method, yeast size
      distributions and population kinetics (single and budding cells, cell clusters)
      are determined during alcoholic fermentations. Combination of image analysis with
      a methylene blue viability test is examined but the staining procedure induces a
      change in the size of the cells. .

PMID- 18612964
TI  - High tolerance of methanogens in granular sludge to oxygen.
AB  - This research assessed the effect of oxygen exposure on the methanogenic activity
      of anaerobic granular sludges. The toxicity of oxygen to acetoclastic methanogens
      in five different anaerobic granular sludges was determined in serum flasks with
      effective gas-to-liquid volumes of 4.65 to 1. The amount of oxygen that caused
      50% inhibition of the methanogenic activity after 3 days of exposure ranged from
      7% to 41% oxygen in the head space. These results indicate that methanogens
      located in granular sludge have a high tolerance for oxygen. The most important
      factor contributing to the tolerance was the oxygen consumption by facultative
      bacteria metabolizing biodegradable substrates. Uptake of oxygen by these
      bacteria creates anaerobic microenvironments where the methanogenic bacteria are
      protected. The results also indicate that methanogens in sludge consortia still
      have some tolerance to oxygen, even in the absence of facultative substrate for
      oxygen respiration.

PMID- 18612968
TI  - A comparative quantitative analysis of cytoarchitecture and minicolumnar
      organization in Broca's area in humans and great apes.
AB  - Broca's area was identified in the inferior frontal gyrus of chimpanzee, bonobo,
      gorilla, and orangutan brains through direct cytoarchitectonic comparison with
      human brains. Across species, Broca's area comprises Brodmann's areas 44 and 45.
      We found that these areas exhibited similar cytoarchitectonic characteristics in
      all species examined. We analyzed the minicolumnar organization of cells in layer
      III of Broca's area in 11 human and 9 great ape specimens. A semiautomated method
      was used to analyze digitized images of histological sections stained for Nissl
      substance. Horizontal spacing distance and gray level index (GLI; or the area
      fraction occupied by cells) were quantified in all images. In contrast to area
      Tpt, the only cortical area for which comparative minicolumnar data have been
      published previously for humans and one of the great apes, we found no population
      level asymmetry, for either horizontal spacing distance or GLI. Only human
      females exhibited a leftward asymmetry in GLI. GLI was lower in humans than in
      great apes (P < 0.001), allowing more space for connectivity in layer III. In
      humans, horizontal spacing distance was greater than in great apes but smaller
      relative to brain size.

PMID- 18612969
TI  - Psychological adjustment and treatment of children and families with parents
      deployed in military combat.
AB  - The effects of the military deployment of parent-soldiers on children and
      families need to be understood in the context of military culture as well as from
      developmental risk for maladjustment. Although research addressing such effects
      is limited in both scope and certainty, we can identify several key factors that
      relate to psychological risk, adjustment, and outcome. Most children are
      resilient to the effects of deployment of at least one of their parents, but
      children with preexisting psychological conditions, such as anxiety and
      depression, may be particularly vulnerable, as well as children with specific
      risk factors, such as child abuse, family violence, or parental substance abuse.
      A series of case vignettes illustrate the psychological adjustment and treatment
      implications for children with parents deployed in support of military combat
      operations.

PMID- 18612970
TI  - Development of a robust GABA(B) calcium signaling cell line using beta-lactamase
      technology and sorting.
AB  - The GABA(B) receptor is a member of the "family 3" G protein coupled receptors.
      The GABA(B) receptors modulate activity inwardly rectifying potassium channels
      and high voltage activated calcium channels. The GABA(B) receptors require
      heterodimerization between two subunits, GABA(B1) and GABA(B2), for functional
      expression. A robust functional calcium cell line was developed that contained
      both the human truncated GABA(B(1b)) and human truncated GABA(B(2)) receptors.
      The cell line was analyzed and sorted using beta-lactamase as a reporter. Single
      cell clones were sorted and isolated using flow cytometry based on high beta
      lactamase expression. The single cell clones were further tested in a 384-well
      calcium mobilization assay using the Fluo-4 AM calcium indicator on the
      fluorescent imaging plate reader system (FLIPR). Twenty-seven clones were grown
      up from single cell collections and 10 clones demonstrated a high response to
      GABA stimulation. The 10 clones were re-evaluated based on agonist dose response
      and EC(50). Clone-16 was identified and utilized in high throughput screening
      (HTS) assay development. Using sorting and beta-lactamase as a reporter, we were
      able to develop a robust, functional cell-based, GABA(B), calcium mobilization
      assay. The cell line described here can be used for high throughput FLIPR
      screening and also to compare and rank the potency and selectivity of agonists,
      antagonists and potentiators of the GABA(B) receptor.

PMID- 18612971
TI  - Assessment of the suitability of a new composite as a bone defect filler in a
      rabbit model.
AB  - To assess the suitability of clinical application of a new composite consisting
      of calcium phosphate cement (CPC), chitosan fibre and gelatin, a bilateral
      supracondyle hole defect (5 mm in diameter) was developed in the femurs of 40 New
      Zealand white rabbits and filled with either the composite or CPC. Macroscopic,
      radiological, histological and histomorphometric evaluations were performed at
      the time points of 1, 3, 6 and 12 months post-operation. New bone formation of
      the composite group was 46.5 +/- 3.2% within 12 months, while that of the CPC
      group was 12.4 +/- 2.7% (p < 0.05). No adverse response was found in either
      group. In addition, it was very interesting that the new bone grew into the
      implant only in the composite group. By histochemical staining we found that
      chitosan fibre was surrounded by monocytes and macrophages after 3 months.
      Overall, our study demonstrated that both CPC and the composite had
      osteoconductive characteristics and good biocompatibility, but the composite
      presented superior bioresorbability and a higher rate of new bone formation.

PMID- 18612972
TI  - Glycogen storage in tissue-engineered cartilage.
AB  - Recent focus in cartilage tissue engineering has been to develop functional
      tissue that can survive after implantation. One such determinant is the ability
      of the engineered tissue to be able to sustain its metabolic activity post
      implantation. In vivo, chondrocytes contain stores of intracellular glycogen to
      support metabolism and it is unknown whether these cells can store glycogen
      during tissue growth in vitro. Thus, the purpose of this study was to determine
      the appropriate nutrient conditions to elicit glycogen storage in tissue
      engineered cartilage. Isolated bovine articular chondrocytes were seeded in
      scaffold-free, 3D culture and grown under different nutrient conditions (glucose
      concentrations and media volumes) for 4 weeks. Intracellular glycogen storage,
      glucose utilization and extracellular matrix (ECM) accumulation of the engineered
      tissues were then evaluated. Glucose concentration (5-10 mM) and media volume (1
      4 ml) had no apparent effect on cartilaginous tissue formation. However, glucose
      consumption by the cells increased in proportion to the volume of medium
      provided. Lactate production was similarly affected but in direct proportion to
      the glucose consumed, indicating a change in glucose utilization. Similarly,
      under elevated medium volume, engineered tissues stained positive for
      intracellular glycogen, which was also confirmed biochemically (1 ml, 1 +/- 2; 2
      ml, 13 +/- 4; 4 ml, 13 +/- 3 microg/construct). The storage of intracellular
      glycogen in engineered cartilage can be elicited by culturing the constructs in
      elevated volumes of medium (>or=1 ml medium/million cells), which might help to
      ensure appropriate metabolic function after implantation.

PMID- 18612973
TI  - On the permissiveness of the abductive theory of method.
AB  - In this article, the author examines Romeijn's (2008) contention that the account
      of theory construction in the abductive theory of scientific method suffers from
      the problem of the underdetermination of theories by empirical evidence.
      Following Romeijn, the author focuses on the issue of underdetermination as it
      affects the method of exploratory factor analysis, the strategy of analogical
      modeling, and the theory of explanatory coherence. The author argues that in each
      case there are sufficient methodological resources available to researchers to
      use these methods to good effect. Additionally, he comments on the normative
      force of the abductive theory of method.

PMID- 18612975
TI  - Effect of operating conditions on solid substrate fermentation.
AB  - In this work the effects of environmental parameters on the performance of solid
      substrate fermentation (SSF) for protein production are studied. These parameters
      are (i) air flow rate, (ii) inlet air relative humidity, (iii) inlet air
      temperature, and (iv) the heat transfer coefficient between the outer wall of the
      fermentor and the air in the incubator. The air flow is supplied to effect
      cooling of the fermented mass by evaporation of water. A dynamic model is
      developed, which permits estimation of biomass content, total dry matter,
      moisture content, and temperature of the fermented matter. The model includes the
      effects of temperature and moisture content on both the maximum specific growth
      rate and the maximum attainable biomass content. The results of the simulation
      are compared with actual experimental data and show good agreement with them. The
      most important conclusions are that (i) the evaporative cooling of the biomass is
      very effective for temperature control and (ii) the air flow rate and the heat
      transfer coefficient have strong effects but they affect the biomass morphology
      and are not controllable easily. Also, a simple technique for the determination
      of the optimum temperature and moisture content profile for cell protein
      production is applied. The simulated biomass production increases considerably
      employing the optimum temperature and moisture content profiles. The ultimate
      goal is to implement the determined effects of the environmental parameters on
      the SSF biomass production and the temperature and moisture variation profiles to
      effectively control the SSF and optimize the biomass production.

PMID- 18612976
TI  - A mathematical model for dynamic simulation of anaerobic digestion of complex
      substrates: focusing on ammonia inhibition.
AB  - A mathematical model for anaerobic degradation of complex organic material, such
      as manure, has been developed. The model includes an enzymatic hydrolytic step
      and four bacterial steps and involves 12 chemical compounds. The model focuses on
      ammonia inhibition and includes a detailed description of pH and temperature
      characteristics in order to accurately simulate free ammonia concentration. Free
      ammonia and acetate constitute the primary modulating factors in the model. The
      model has been applied for the simulation of digestion of cattle manure in
      continuously stirred tank reactors (CSTRs), and results compare favorably with
      experimental data.

PMID- 18612977
TI  - Measurements of conformational changes during adhesion of lipid and protein
      (polylysine and S-layer) surfaces.
AB  - The adhesion forces between various surfaces were measured using the "surface
      forces apparatus" technique. This technique allows for the thickness of surface
      layers and the adhesion force between them to be directly measured in controlled
      vapor or liquid environments. Three types of biological surfaces were prepared by
      depositing various lipid-protein monolayers (with thicknesses ranging from 1 to 4
      nm) on the inert, molecularly smooth mica surface: (i) hydrophobic lipid
      monolayers; (ii) amphiphilic polyelectrolyte surfaces of adsorbed polylysine; and
      (iii) deposited bacterial S-layer proteins. The adhesion, swelling, and wetting
      properties of these surfaces was measured as a function of relative humidity and
      time. Initial adhesion is due mainly to the van der Waals forces arising from
      nonpolar (hydrophobic) contacts. Following adhesive contact, significant
      molecular rearrangements can occur which alter their hydrophobic-hydrophilic
      balance and increase their adhesion with time. Increased adhesion is generally
      enhanced by (i) increased relative humidity (or degree of hydration); (ii)
      increased contact time; and (iii) increased rates of separation. The results are
      likely to be applicable to the adhesion of many other biosurfaces, and show that
      the hydrophobicity of a lipid or protein surface is not an intrinsic property of
      that surface but depends on its environment (e.g., on whether it is in aqueous
      solution or exposed to the atmosphere), and on the relative humidity of the
      atmosphere. It also depends on whether the surface is in adhesive contact with
      another surface and-when considering dynamic (nonequilibrium) conditions-on the
      time and previous history of its interaction with that surface.

PMID- 18612978
TI  - Immobilization of beta-galactosidase for application in organic chemistry using a
      chelating peptide.
AB  - The strong interaction of hexa-histidine fusion proteins with metal chelate
      adsorbents was utilized to immobilize beta-galactosidase with a hexa-histidine
      peptide at the N-terminus to the Ni(2+)-nitrilotriacetic acid adsorbent. The
      fusion protein was cloned and expressed in Escherichia coli. The purified soluble
      fusion protein showed the same specific activity as the purified beta
      galactosidase and retained 64 percent of its beta-galactosidase activity when
      bound to the adsorbent. To demonstrate the potential of the immobilized beta
      galactosidase in organic chemistry, allyl-beta-D-galactosidase was synthesized
      from lactose and allyl alcohol on a gram scale. The same enzyme preparation was
      reused in three subsequent batches to prepare the model compound with high yield.

PMID- 18612979
TI  - Cell retention-chemostat studies of hybridoma cells-analysis of hybridoma growth
      and metabolism in continuous suspension culture in serum-free medium.
AB  - The steady-state metabolic parameters for a hybridoma cell line have been
      determined in continuous suspension-perfusion culture over a wide range of
      perfusion rates and cell bleed rates. Significant increases in viable cell
      concentrations and volumetric productivities were achieved at high perfusion
      rates and low cell bleed rates. At the low growth rates examined in this study,
      cellular metabolism shifted to become more oxidative, and as a result, the
      fraction of consumed substrate converted to inhibitory metabolic by-products was
      reduced. Specific antibody productivity was found to be non-growth associated.

PMID- 18612980
TI  - Lipase activity in vesicular systems: characterization of candida cylindracea
      lipase and its activity in polymerizable dialkylammonium surfactant vesicles.
AB  - Lipase from Candida cylindracea (CCL) was incorporated into polymerizable
      positively charged dialkylammonium bromide surfactant vesicles. The enzyme was
      incorporated by the use of the dehydration-rehydration method or by incubation.
      In the latter case, trapping efficiencies of up to 100% could be obtained.
      Activities of free and vesicle-incorporated CCL were tested for three
      triglycerides: triacetin, tributyrin, and tricaprylin. Enzyme activity was lowest
      in homogeneous mixtures (triacetin and small concentrations of tributyrin) and
      highest in heterogeneous mixtures (tricaprylin and high concentrations of
      tributyrin). Entrapment in vesicular systems is advantageous, especially in
      homogeneous reaction mixtures and in the case of the production of insoluble
      fatty acid (caproate), because inhibition by the acid can be suppressed. The
      influence of several surface-active additives, including vesicles, on the
      activity of lipase in triglyceride assays was tested. Vesicles have a positive
      influence on the activity, whereas other positively charged additives act as
      inhibitors. In the case of tricaprylin assays, the positively charged additives
      increase the activity. Finally, tryptic digestion for free and incorporated CCL
      were compared. Free CCL is readily inactivated, whereas incorporated enzyme is
      protected from proteolytic degradation.

PMID- 18612981
TI  - Fed-batch cultivation of recombinant escherichia coli JM103 and production of the
      fusion protein SPA::EcoRI in a 60-L working volume airlift tower loop reactor.
AB  - SPA::EcoRI fusion protein was produced by Escherichia coli JM103 carrying the
      multicopy expression plasmid pMTC48, the multicopy repressor plasmid pRK248, and
      the multicopy protection plasmid pEcoR4 in a 60-L working volume airlift tower
      loop reactor on M9 minimal medium with glucose. Cell mass concentration, total
      cell count, number of colony-forming units, specific growth rate, yield
      coefficient, and metabolite (acetate, pyruvate, succinate, lactate, ethanol)
      concentrations were monitored during the growth phase and gene expression. Gene
      expression was induced by temperature shift or chemically by isopropyl
      thiogalactosidase in the airlift tower loop reactor (ALTR) at constant
      cultivation time and in a small stirred tank reactor at different cultivation
      times. During induction, the cultivation medium was supplemented with
      concentrated Luria-Bertani (LB) medium. The intracellular enzyme activity was
      evaluated as a function of the time after the start of the induction. It was
      found that the reduction of the glucose concentration and increase of the
      dissolved oxygen concentration reduced the acetate produced and increased the
      intracellular enzyme activity.

PMID- 18612982
TI  - Observations of aerobic, growing escherichia coli metabolism using an on-line
      nuclear magnetic resonance spectroscopy system.
AB  - An experimental system has been constructed which enables on-line measurements of
      phosphorus-31 ((31)P) nuclear magnetic resonance (NMR) spectra for growing
      bacterial suspensions under anaerobic or aerobic conditions. A sample stream from
      a laboratory bioreactor is circulated to the NMR sample chamber in a gas exchange
      system which permits maintenance of aerobic conditions for high-cell-density
      cultures. (31)P NMR spectra with resolution comparable with those obtained
      traditionally using dense, concentrated, nongrowing cell suspensions can be
      obtained at cell densities above 25 g/L with acquisition times ranging from 14 to
      3 minutes which decline as cell density increases. This system has been employed
      to characterize the changes in intracellular state of a stationary phase culture
      which is subjected to a transition from aerobic to anaerobic conditions. Both
      intracellular NTP level and cytoplasmic pH are substantially lower under
      anaerobic conditions. Also, the system has been employed to observe the response
      of a growing culture to external addition of acetate. Cells are able to maintain
      pH difference across the cytoplasmic membrane at extracellular acetate
      concentrations of 5 and 10 g/L. However, acetate concentrations of 20 g/L cause
      collapse of the transmembrane DeltapH and sharp reduction of the growth rate of
      the culture. The experimental configuration described should also permit NMR
      observations of many other types of microbial cultures and of other nuclei.

PMID- 18612983
TI  - Investigation of subpopulation heterogeneity and plasmid stability in recombinant
      escherichia coli via a simple segregated model.
AB  - Many microbial and cell cultures exhibit phenomena that can best be described
      using a segregated modeling approach. Heterogeneties are more marked in
      recombinant cell cultures because subpopulations, which often exhibit different
      growth and productivity characteristics, are more easily identified by selective
      markers. A simple segregated mathematical model that simulates the growth of
      recombinant Escherichia coli cells is developed. Subpopulations of different
      growth rate, plasmid replication rate, and plasmid segregation probability are
      explicitly considered. Results indicate that a third mechanism of plasmid
      instability, referred to here as a "downward selective pressure," is significant
      when describing plasmid loss in batch and chemostat cultures. Also, the model
      agrees well with experimental data from cultures under antibiotic selective
      pressure. Finally, model simulations of chemostat cultures reveal the importance
      of initial conditions on culture stability and the possible presence of nonrandom
      partitioning functions.

PMID- 18612984
TI  - Production of recombinant proteins in high-density insect cell cultures.
AB  - The effect of the growth phase of Spodoptera frugiperda (Sf9) cells on the
      production of recombinant proteins (beta-galactosidase and glucocerebrosidase)
      was investigated. Cells infected with the recombinant Autographa californica
      nuclear polyhedrosis virus at the late exponential and stationary phases yielded
      low quantities of expressed protein. Highest enzyme yields were obtained using
      Sf9 cells from the early exponential phase (0.9 mg beta-galactosidase/10(6) cells
      and 1.7 microg glucocerebrosidase/10(6) cells). Infection of resuspension of
      cells collected from various phases of growth in fresh medium resulted in 75%
      restoration of maximal expression levels. This finding suggested either nutrient
      limitation or waste product accumulation as the cause of the decrease in
      productivity at the latter phases of growth. Further experiments revealed that
      the highest productivity levels could be obtained with cultures of Sf9 cells
      grown in a fermentor to a cell concentration of 4 x 10(6) mL(-1). The medium
      needed to be replaced prior to infection with the recombinant virus and
      supplemented with a mixture of glucose, L-glutamine, and yeastolate
      ultrafiltrate.

PMID- 18612985
TI  - Expression of epoxide hydrolase in insect cells: a focus on the infected cell.
AB  - Insect cell culture and the baculovirus vector expression system have emerged to
      be a promising production technique for heterologous proteins. In this article,
      expression characteristics for membrane-bound epoxide hydrolase are examined. A
      generic process is presented whereby cells are grown in serum-free media
      supplemented with serum and then resuspended in serum-free media to simplify
      purification after infection. The infected cells retain significant metabolic
      activity during the postinfection stage. Thus, maintaining nutrient supply during
      the postinfection period is critical, and a low stirring rate will result in
      oxygen depletion and shift the metabolism of the infected cells toward lactate
      production which then lowers product yield. This is the first report indicating
      that glucose is supplied from sucrose decomposition and then metabolized for
      viral DNA and recombinant protein production in recombinant baculovirus insect
      expression system.

PMID- 18612986
TI  - Loss of antibody productivity is highly reproducible in multiple hybridoma
      subclones.
AB  - An immunoglobulin G (IgG(2b)) producing hybridoma cell line (S3H5/gamma2bA2) was
      cloned and subcloned. Twenty subclones were grown in parallel while being adapted
      in a stepwise fashion to serum-free medium. Following adaptation to serum-free
      medium, it was found that 16 of the 20 subclones remained at a relatively
      constant proportion of nonproducing cells. Three of the remaining subclones
      transiently deviated from this balance but eventually returned toward this
      population composition. One subclone continued to lose productivity. A population
      balance was reached at approximately 8% of the population being nonproducers. The
      loss of antibody productivity was thus highly reproducible.

PMID- 18612987
TI  - Subzero temperature operating biosensor utilizing an organic solvent and
      quinoprotein glucose dehydrogenase.
AB  - A subzero temperature operating biosensor was constructed using immobilized
      quinoprotein glucose dehydrogenase (PQQGDH), glassy carbon electrode, soluble
      electron mediator (ferrocene monocarboxylic acid), and an organic solvent,
      ethylene glycol, as an antifreezing reagent. Using this biosensor, glucose
      concentration can be determined even at -7 degrees C. At this temperature, the
      response was 20% of that obtained at 20 degrees C. This is the first study
      describing a subzero temperature operating biosensor.

PMID- 18612988
TI  - A bioassay of thyrotrophin by photografted mammalian cells onto polymeric
      supports.
AB  - Viable and functionally responsive human thyroid follicular cells, suspended in a
      commercial polyester acrylate diluted with tripropyleneglycol diacrylate,
      photoinitiated, and photocatalyzed with a proprietary photocatalytic system based
      on a synergic mixture of vanadium (V) t-butoxide and i-propoxide, have been
      immobilized as monolayers onto polystyrene plates. Bioassay of thyrotrophin in
      immobilized cell cultures yielded, by log-log plot of the dose-response curve, a
      slope (0.92 +/- 0.02) in close agreement with that (0.91) reported for cells
      immobilized by physical adsorption. The decisive role of photocatalyst in the
      photografting procedure has also been shown experimentally. A mechanism is
      suggested by which cells are anchored, rapidly and with stable chemical bonds,
      onto one of the two acrylate functions of the monomer-prepolymer mixture, the
      other one being simultaneously responsible for photochemical grafting onto the
      support.

PMID- 18612989
TI  - Some factors determining protein aggregation during ultrafiltration.
AB  - The factors contributing to protein aggregation in albumin ultrafiltration were
      investigated as a function of operation conditions. The nature of protein
      deposits was examined by electron microscopy. Protein aggregation appears to
      occur as a result of rapid supersaturation of protein molecules and high solvent
      velocity (shear) in the concentrated layer near the membrane surface. The shear
      occurring in the solvent flow on the membrane surface probably unfolds protein
      molecules and thus promotes flocculation due to collision between particles.

PMID- 18612990
TI  - Standardization and optimization of multiparameter intracellular cytokine
      staining.
AB  - Intracellular cytokine staining (ICS) is a common method for rapid quantitation
      of cytokine-producing antigen-specific T cells. T cell production of IFNgamma in
      particular, and more recently IL-2 as well, is often taken as a measure of
      vaccine immunogenicity in experimental vaccine trials. As more fluorochromes
      become available for use in ICS and other applications detecting intracellular
      markers, the selection of optimal fluorochrome combinations becomes
      correspondingly more complicated. Additionally, as more sophisticated flow
      cytometers become available, more attention is being paid to potential result
      variability from one instrument to another. This review summarizes an oral
      presentation given at MASIR 2008, January 30-Feb 1, 2008, in La Plagne, France.
      We focus on issues associated with multiparameter (>four color) flow cytometry,
      including matching antibody specificities with available fluorochromes and
      techniques to optimize fluorochrome combinations. We examine issues specific to
      intracellular staining as well as broader topics such as instrument setup,
      experimental controls, sample management, and analysis of multiparameter data
      sets. Particular emphasis is placed on the use of lyophilized cells, antibodies,
      beads, peptides, etc. (collectively known as "lyoplates"), which can decrease
      experiment-to-experiment variability as well as processing time. Most clinical
      trials compile results from multiple testing sites, using data that was acquired
      on-site in each location. We present data from two different ongoing multi
      laboratory standardization studies, one involving 15 laboratories and one
      involving nine. We identify issues of variability and, where possible, offer
      solutions.

PMID- 18612991
TI  - Use of MHC class II tetramers to investigate CD4+ T cell responses: problems and
      solutions.
AB  - MHC-class I tetramers technology enabled the characterization of peptide-specific
      T cells at the single cell level in a variety of studies. Several laboratories
      have also developed MHC-class II multimers to characterize Ag-specific CD4+ T
      cells. However, the generation and use of MHC-class II multimers seems more
      problematic than that of MHC-I multimers. We have generated HLA-DR*1101 tetramers
      in a versatile empty form, which can be loaded after purification with peptides
      of interest. We discuss the impact of critical biological and structural
      parameters for the optimal staining of Ag-specific CD4+ T cells using HLA-DR*1101
      tetramers, such as: (i) activation state of CD4+ T cells; (ii) membrane
      trafficking in the target CD4+ T cells; (iii) binding characteristics of the
      loaded CD4 epitope. Our data indicate that reorganization of TCR on the plasma
      membrane upon CD4+ T cell activation, as well as an homogenous binding frame of
      the CD4 epitopes to the soluble HLA-DR monomer, are critical for a stable TCR/MHC
      class II tetramer interaction. These factors, together with the low frequencies
      and affinities of specific CD4+ T cells, explain the need for in vitro expansion
      or ex vivo enrichment of specific T cells for the optimal visualization with MHC
      class II tetramers.

PMID- 18612992
TI  - Enhanced red and near infrared detection in flow cytometry using avalanche
      photodiodes.
AB  - Polychromatic flow cytometry enables detailed identification of cell phenotype
      using multiple fluorescent parameters. The photomultiplier tubes (PMTs) used to
      detect fluorescence in current instruments limit the sensitivity in the long
      wavelength spectral range. We demonstrate the flow cytometric applications of
      silicon avalanche photodiodes (APDs), which have improved red sensitivity and a
      working fluorescence detection range beyond 1,000 nm. A comparison of the
      wavelength-dependent performance of the APD and PMT was carried out using pulsed
      light-emitting diode sources, calibrated test beads, and biological samples. A
      breadboard flow cytometer test bench was constructed to compare the performance
      of PMTs and APD detectors. The APD used an additional amplifier stage to match
      the internal gain of the PMT. The resolution of the APD and PMT was compared for
      flow cytometry applications using a pulsed light-emitting diode source over the
      500-1060 nm spectral range. These measurements showed the relative changes in the
      signal-to-noise performance of the APD and PMT over a broad spectral range. Both
      the APD and PMTs were used to measure the signal-to-noise response for a set of
      six peak calibration beads over the 530-800 nm wavelength range. CD4-positive
      cells labeled with antibody-conjugated phycoerythrin or 800 nm quantum dots were
      identified by simultaneous detection using the APD and the PMT. The ratios of the
      intensities of the CD4- and CD4+ populations were found to be similar for both
      detectors in the visible wavelengths, but only the APD was able to separate these
      populations at wavelengths above 800 nm. These measurements illustrate the
      differences in APD and PMT performance at different wavelengths and signal
      intensity levels. While the APD and PMT show similar signal-to-noise performance
      in the visible spectral range, the dark noise of the APD detector reduces the
      sensitivity at low signal levels. At wavelengths longer than 650 nm, the high
      quantum efficiency of the APD contributes to better signal-to-noise performance.
      The APD detector provides enhanced performance in the long wavelength region and
      may be used to extend the working range of the flow cytometer beyond 1,000 nm.

PMID- 18612993
TI  - Virtual reality exposure therapy for active duty soldiers.
AB  - Virtual reality exposure (VRE) therapy is a promising treatment for a variety of
      anxiety disorders and has recently been extended to the treatment of
      posttraumatic stress disorder (PTSD). In this article, the authors briefly review
      the rationale for VRE and its key processes. They illustrate the treatment with
      an active-duty Army soldier diagnosed with combat-related PTSD. Six sessions of
      VRE were provided using an immersive simulation of a military convoy in Iraq.
      Self-reported PTSD symptoms and psychological distress were reduced at
      posttreatment relative to pretreatment reports, as assessed by the PTSD Checklist
      Military Version and the Behavior and Symptom Identification Scale-24. The case
      outcomes parallel those reported in the research with other disorders and suggest
      the applicability of VRE in treating active duty soldiers with combat-related
      PTSD.

PMID- 18612994
TI  - Eye movement desensitization and reprocessing (EMDR) in the treatment of war
      veterans.
AB  - Recent practice guidelines and meta-analyses have designated eye movement
      desensitization and reprocessing (EMDR) as a first-line treatment for trauma. Eye
      movement desensitization and reprocessing is an eight-phase therapeutic approach
      guided by an information-processing model that addresses the combat veteran's
      critical incidents, current triggers, and behaviors likely to prove useful in his
      or her future. Two case examples of combat veterans illustrate the ability of
      EMDR to achieve symptom reduction in a variety of clinical domains (e.g.,
      anxiety, depression, anger, physical pain) simultaneously without requiring the
      patient to carry out homework assignments or discuss the details of the event.
      The treatment of phantom limb pain and other somatic presentations is also
      reviewed. The ability of EMDR to achieve positive effects without homework
      indicates that it can be effectively employed on consecutive days, making it
      especially useful during combat situations.

PMID- 18612995
TI  - Ab initio simulation of the IR spectra of pyrope, grossular, and andradite.
AB  - IR spectra of pyrope Mg(3)Al(2)Si(3)O(12), grossular Ca(3)Al(2)Si(3)O(12) and
      andradite Ca(3)Fe(2)Si(3)O(12) garnets were simulated with the periodic ab initio
      CRYSTAL code by adopting an all-electron Gaussian-type basis set and the B3LYP
      Hamiltonian. Two sets of 17 F(1u) Transverse Optical (TO) and Longitudinal
      Optical (LO) frequencies were generated, together with their intensities. Because
      the generation of LO modes requires knowledge of the high frequency dielectric
      constant epsilon(infinity) and Born effective charges, they were preliminary
      evaluated by using a finite field saw-tooth model and well localized Wannier
      functions, respectively. As a by-product, the static dielectric constant
      epsilon(0) was also obtained. The agreement of the present calculated wavenumbers
      (i.e. peak positions) with the available experimental data is excellent, in that
      the mean absolute difference for the full set of data smaller than 8 cm(-1).
      Missing peaks in experimental spectra were found to correspond to modes with low
      calculated intensities. Correspondence between TO and LO modes was established on
      the basis of the overlap between the eigenvectors of the two sets and similarity
      of isotopic shifts; as result, the so called LO-TO splitting could be determined.
      Animation of the normal modes was employed to support the proposed pairing.

PMID- 18612996
TI  - Gaussian basis set of double zeta quality for atoms K through Kr: application in
      DFT calculations of molecular properties.
AB  - Contracted basis sets of double zeta (DZ) quality for the atoms from K to Kr are
      presented. They were determined from fully optimized basis sets of primitive
      Gaussian-type functions generated in atomic Hartree-Fock calculations. Sets of
      Gaussian polarization functions optimized at the Moller-Plesset second-order
      level were added to the DZ basis set. This extends earlier work on segmented
      contracted DZ basis set for atoms H-Ar. From this set, using the BP86 nonhybrid
      and B3LYP hybrid functionals, dissociation energy, geometric parameters, harmonic
      vibrational frequency, and electric dipole moment of a set of molecules were
      calculated and compared with results obtained with other basis sets and with
      experimental data reported in the literature. In addition, (57)Fe and (77)Se
      nuclear magnetic resonance chemical shifts in Fe(C(5)H(5))(2), H(2)Se, and CSe(2)
      were calculated using density functional theory and gauge-including atomic
      orbitals and, then, compared with theoretical and experimental values previously
      published in the literature. Except for chemical shift, one verifies that our
      results give the best agreement with experimental and benchmark values.

PMID- 18612997
TI  - ARHI, as a novel suppressor of cell growth and downregulated in human
      hepatocellular carcinoma, could contribute to hepatocarcinogenesis.
AB  - The identification of cancer genes differentially expressed in hepatocellular
      carcinoma (HCC) plays an important role in understanding the molecular mechanisms
      of hepatocarcinogenesis. Here, ARHI gene expression was analyzed by real-time RT
      PCR and it was significantly downregulated in 33 of the 42 (78.6%, more than two
      folds) HCC specimens compared with adjacent noncancerous livers (P < 0.01). In
      addition, ARHI expression was reduced in some HCC samples at protein level
      confirmed by immunohistochemistry. Furthermore, our data suggested that the
      overexpression of ARHI can significantly inhibit cell growth and colony formation
      of Hep3B cells (P < 0.01), whilst silencing endogenous ARHI gene by RNAi could
      promote cell growth of Huh-7 and Focus. LOH of microsatellite markers D1S2806 and
      D1S2803 was only found in 2.4% (1 of 42 HCCs) of HCC cases. The expression of
      ARHI was obviously re-expressed in some HCC cells, Bel-7402, Bel-7405, QGY-7703
      and Hep3B, by a demethylation agent, 5-aza-2'-deoxycytidine (DAC). DNA
      hypermethylation within ARHI promoter was identified in 47.1% of HCC specimens
      without ARHI expression. Our current observations provide evidences that ARHI
      downregulated in HCCs could play a role in liver cancer via acting as a tumor
      suppressor gene, which mainly was triggered by the epigenetic events in HCC
      specimens.

PMID- 18612999
TI  - Clinical validity of Fuld Object Memory Evaluation to screen for dementia in a
      Chinese society.
AB  - OBJECTIVES: Fuld Object Memory Evaluation (FOME) evaluates the episodic memory
      functions of encoding, storage, and recall across five recall trials and a
      delayed recall trial. This study examined the clinical validity of FOME as a
      screening tool for dementia in older Chinese adults. METHOD: The psychometric
      properties and the discriminative power of FOME were examined in a convenience
      sample of 192 community-dwelling older individuals, of which 57 were diagnosed
      with dementia. The influence of age and education on the FOME performance was
      also estimated. RESULTS: The test-retest reliability and parallel-form
      reliability of FOME were excellent, with Intraclass Correlation Coefficients
      ranging from 0.91-0.96. Good convergent validity of FOME was established with
      Mini-Mental State Examination (r(p) = 0.69-0.74), and the Memory subscale and the
      Initiation/Perseveration subscale of Dementia Rating Scale (r(p) = 0.63-0.74).
      The FOME total retrieval (TR) score and delayed recall (DR) score demonstrated
      good discriminative power in differentiating dementia from normal cognitive
      functioning, with area under the curve values of 0.97 and 0.93 respectively. The
      optimal cut-off scores suggested for TR and DR were 31 (93% sensitivity, 90
      specificity) and 7 (91% sensitivity, 82% specificity), respectively. The
      performance of the FOME was not influenced by the educational level. CONCLUSIONS:
      The results suggest that the FOME is a reliable and valid instrument to screen
      for dementia in older community-dwelling Chinese adults. The absence of the
      effects of education on the assessment performance makes FOME a clinically useful
      instrument for older adults with limited education.

PMID- 18612998
TI  - A profile of impaired insulin degradation in relation to late-life cognitive
      decline: a preliminary investigation.
AB  - OBJECTIVE: Insulin degradation pathways may be related to Alzheimer's disease
      pathology. In preliminary analyses, we considered the relation of combined lower
      insulin secretion (c-peptide) and higher insulin--possibly a phenotype for
      impaired insulin degradation--to cognitive decline. METHOD: Fasting plasma c
      peptide and insulin were measured in 1,187 non-diabetic Nurses' Health Study
      participants (mean age = 64 years). Cognitive testing began 10 years later.
      Participants completed three repeated assessments (over an average span of 4.4
      years) of verbal memory, a strong predictor of Alzheimer disease development. C
      peptide and insulin distributions were dichotomized at their medians to create
      four cross-tabulated categories. Multivariable linear mixed effects models were
      used to relate c-peptide/insulin categories to cognitive decline. RESULTS:
      Compared to the lower c-peptide/lower insulin group, women with lower c
      peptide/higher insulin had a significantly faster rate of verbal memory decline:
      the mean difference was -0.05 units/year (95% CI -0.09,-0.01). This mean
      difference was similar to that which we found for women 5 years apart in age,
      indicating that having a profile of lower c-peptide/higher insulin appeared
      cognitively equivalent to aging by five years on tests of verbal memory. For
      women with higher c-peptide/higher insulin, the estimated mean difference in
      decline compared to those in the lower c-peptide/lower insulin group was
      statistically significant, but slightly lower, at -0.04 units/year (95% CI: 
      0.07,-0.02). CONCLUSION: These preliminary analyses of a possible phenotype of
      impaired insulin degradation provide supportive evidence that deficits in insulin
      degradation may be related to late-life verbal memory decline.

PMID- 18613000
TI  - IRMPD spectra of Gly.NH4 + and proton-bound betaine dimer: evidence for the
      smallest gas phase zwitterionic structures.
AB  - Zwitterionic structures exist extensively in biological systems and the electric
      field resulting from zwitterion formation is the driving force for determination
      of the properties, function and activity of biological molecules, such as amino
      acids, peptides and proteins. It is of considerable interest and import to
      investigate the stabilization of zwitterionic structures in the gas phase.
      Infrared multiple photon dissociation (IRMPD) spectroscopy is a very powerful and
      sensitive technique, which may elucidate clearly the structures of both ions and
      ionic clusters in the gas phase, since it provides IR vibrational fingerprint
      information. The structures of the clusters of glycine and ammonium ion and of
      the betaine proton-bound homodimer have been investigated using IRMPD
      spectroscopy, in combination with electronic structure calculations. The
      experimental and calculated results indicate that zwitterionic structure of
      glycine may be effectively stabilized by an ammonium ion. This is the smallest
      zwitterionic structure of an amino acid to be demonstrated in the gas phase. On
      the basis of the experimental IRMPD and calculated results, it is very clear that
      a zwitterionic structure exists in the proton-bound betaine dimer. The proton is
      bound to one of the carboxylate oxygens of betaine, rather than being equally
      shared. Investigations of zwitterionic structures in the isolated state are
      essential for an understanding of the intrinsic characteristics of zwitterions
      and salt bridge interactions in biological systems.

PMID- 18613001
TI  - Two distinct tumor phenotypes isolated from glioblastomas show different MRS
      characteristics.
AB  - We have developed a human brain tumor model in immunodeficient rats that
      gradually changes its phenotype by serial passages in vivo, from a highly
      infiltrative, non-angiogenic one with numerous stem cell markers [low-generation
      (LG) tumor] to a more typical glioblastoma one with extensive angiogenesis and
      necrosis [high-generation (HG) tumor]. In this study we determined the metabolic
      properties of these two phenotypes, using (1)H MRS. The LG tumors showed an
      intact blood-brain barrier and normal vascular morphology, as shown by MRI and
      Hoechst staining. In contrast, the HG tumors exhibited vascular leakage and
      necrosis. The animals with HG tumor had raised concentrations of choline and myo
      inositol, and decreased concentrations of glutamate and N-acetylaspartate. In the
      LG tumor group, similar changes in metabolic concentrations were detected,
      although the alterations were more pronounced. The LG tumors also had higher
      concentrations of choline, taurine, and lactate. Subdividing the LG and HG tumors
      into large and small tumors revealed a significant increase in choline and
      decrease in glutamate as the LG tumors increased in size. Our results show that
      metabolic profiles produced by (1)H MRS can be used to distinguish between two
      distinct glioblastoma phenotypes. More pronounced anaerobic metabolism was
      present in the LG stem-cell-like tumors, suggesting a more malignant phenotype.

PMID- 18613002
TI  - Myoedema in anorexia nervosa: a useful clinical sign.
AB  - When significant weight loss occurs in anorexia nervosa, routine physical
      examination may reveal the striking phenomenon of myoedema or muscle mounding.
      This refers to the way in which a localised short-lasting swelling may be induced
      in a voluntary muscle as a result of tactile percussion, ideally with a patellar
      hammer. The present case report describes this finding in a patient with anorexia
      nervosa and discusses its physiological and clinical significance. It is
      suggested that as a clinical sign myoedema may be of value in the management of
      anorexia nervosa by challenging the denial of illness which is so characteristic
      of it.

PMID- 18613003
TI  - Stable isotopes may provide evidence for starvation in reptiles.
AB  - Previous studies have attempted to correlate stable isotope signatures of tissues
      with the nutritional condition of birds, mammals, fishes, and invertebrates.
      Unfortunately, very little is known about the relationship between food
      limitation and the isotopic composition of reptiles. We examined the effects that
      starvation has on delta13C and delta15N signatures in the tissues (excreta,
      carcass, scales, and claws) of six, distantly related squamate reptiles (gaboon
      vipers, Bitis gabonica; ball pythons, Python regius; ratsnakes, Elaphe obsoleta;
      boa constrictors, Boa constrictor; western diamondback rattlesnakes, Crotalus
      atrox, and savannah monitor lizards, Varanus exanthematicus). Analyses revealed
      that the isotopic composition of reptile carcasses did not change significantly
      in response to bouts of starvation lasting up to 168 days. In contrast, the
      isotopic signatures of reptile excreta became significantly enriched in 15N and
      depleted in 13C during starvation. The isotopic signatures of reptile scales and
      lizard claws were less indicative of starvation time than those of excreta. We
      discuss the physiological mechanisms that might be responsible for the starvation
      induced changes in 13C and 15N signatures in the excreta, and present a mixing
      model to describe the shift in excreted nitrogen source pools (i.e. from a labile
      source pool to a nonlabile source pool) that apparently occurs during starvation
      in these animals. The results of this study suggest that naturally occurring
      stable isotopes might ultimately have some utility for characterizing nitrogen
      and carbon stress among free-living reptiles.

PMID- 18613004
TI  - A facile microdialysis interface for on-line desalting and identification of
      proteins by nano-electrospray ionization mass spectrometry.
AB  - The adverse effect of salts, especially inorganic salts, on electrospray
      ionization mass spectrometry (ESI-MS) is one of the most serious obstacles that
      might limit its application. Among the numerous desalting approaches, the
      microdialysis technique is favorable for large molecules, such as proteins. In
      this work, employing a hollow fiber membrane of cellulose acetate (MWCO 3000 Da),
      a simple, facile and efficient microdialysis interface with the dead volume of
      less than 1 microL was constructed for the on-line desalting and identification
      of proteins dissolved in high salt concentration buffer by nano-ESI-MS.
      Furthermore, with counterflow added, the desalting procedure was accelerated, and
      could be finished within 1 min. This system was successfully applied to the
      analysis of myoglobin dissolved in either high concentration ammonium acetate or
      sodium chloride buffer. The experimental results showed that, by using such a
      microdialysis interface, the salt concentration, even as high as 1 M, could be
      decreased by at least 2 orders of magnitude, while sample loss was less than 10%,
      demonstrating the potential of such an interface in broadening the application of
      nano-ESI-MS in the analysis of large molecules.

PMID- 18613005
TI  - Alzheimer's disease progression in the oldest old compared to younger elderly
      patient: data from the REAL.FR study.
AB  - OBJECTIVE: Although population-based studies have revealed marked increases in
      the prevalence and incidence of dementia, particularly in older age groups,
      longitudinal studies of cognitive change have been less frequently conducted. The
      aim of this study is to describe the progression of Alzheimer's disease (AD) in
      the oldest old (>or=85 years) and to compare it with the younger elderly.
      METHODS: A cohort of 114 AD patients >or=85 years old and 572 AD patients <85
      years living in the community at inclusion were monitored over 2 years in 16
      centers of the French AD network (REAL.FR study). Each subject underwent
      extensive medical examination including functional (Activities of Daily Living or
      ADL) and neuropsychological evaluations (including Mini Mental Status Evaluation
      or MMSE) every 6 months. RESULTS: The observed decrease in MMSE performance in
      patients >or=85 was -4.18 +/- 0.63 points during the 2-year follow-up (vs -4.62
      +/- 0.25 in the younger group) with no statistically significant differences
      between the two groups. After adjusting for confounding factors, ADL score
      declined faster in the oldest old than in individuals <85 years old during the 2
      year follow-up: -1.73 +/- 0.19 vs -1.27 +/- 0.08 (p = 0.0309). CONCLUSIONS: Our
      study showed, that while the progression of cognitive impairment was identical in
      both groups, after adjustment for variables related both to age and dependency,
      the progression of dependency was more rapid in those over 85 years old.

PMID- 18613007
TI  - Intergroup relations and home range use in Verreaux's sifaka (Propithecus
      verreauxi).
AB  - Relationships between neighboring groups feature prominently in socioecological
      theory, but few empirical studies have focused on the effects of neighbors on the
      behavior of primates. Interactions between neighboring groups are most
      conspicuous during intergroup encounters, but the likelihood of encounters with
      neighbors can also affect ranging and activity patterns indirectly, and, as a
      result, behavioral patterns in areas of exclusive use may differ from those in
      overlap areas of adjacent home ranges. The aim of this study was to examine
      intergroup relations and spatial variation in home range use in Verreaux's sifaka
      (Propithecus verreauxi) during the annual mating season. Based on 230 hr of focal
      animal data collected from ten members of five adjacent groups, we found that
      behavioral patterns and patterns of resource utilization were not markedly
      different between areas of exclusive use and overlap areas of adjacent home
      ranges. Group cohesion tended to be higher in overlap than in core areas, but the
      proportion of time spent resting and foraging did not differ between these two
      areas. However, dominant males exhibited a higher scent-marking rate in overlap
      areas. Observations during intergroup encounters revealed that chases between
      males occurred frequently, whereas fights involving physical contact were not
      observed. We also found that the intergroup dominance hierarchy depended on the
      relative group size or the number of males in each group, with groups of lower
      dominance rank exhibiting a tendency to sleep proportionally more often in their
      core areas. The results of this study suggest that in primate species with a
      moderate level of intergroup aggression, such as Verreaux's sifaka, the
      possibility of encountering neighbors in areas of home range overlap does not
      exert strong influence on their behavior and resource utilization.

PMID- 18613006
TI  - Rapid pulmonary delivery of inhaled tobramycin for Pseudomonas infection in
      cystic fibrosis: a pilot project.
AB  - BACKGROUND: Patients with cystic fibrosis spend as much 30 min a day inhaling
      tobramycin. Could a new rapid system deposit the equivalent amount of tobramycin
      faster? METHODS: Six healthy adult males inhaled 5 ml (300 mg) of tobramycin from
      a breath enhanced nebulizer and either 125 mg (n = 3) or 150 mg (n = 3) from a
      vibrating membrane system with a large or small aerosol mixing chamber
      respectively. A radiolabel was added to the solution and shown to "track" with
      the tobramycin. Imaging was done with a dual headed gamma camera. Because the
      radiolabel will be cleared by mucociliary action during administration,
      algorithms were developed to allow the comparison of a slower system to a faster
      one. RESULTS: Both formulations were well tolerated. The lung deposition was 16.6
      +/- 3.2% (mean +/- SD) of the charge dose delivered in 10.9 +/- 1.0 min for the
      breath enhanced nebulizer versus 32.0 +/- 5.1% delivered in 2.5 +/- 0.4 min from
      the vibrating membrane system. The absolute pulmonary delivery of tobramycin was
      49.9 +/- 9.6 versus 43.9 +/- 4.8 mg for the two systems respectively, differences
      that were statistically significant (pair t-test) but unlikely to be clinically
      significant. There was a similar deposition of tobramycin for the 125 and 150 mg
      dose. CONCLUSIONS: It is possible to deliver an equivalent amount of tobramycin
      in a shorter period of time with the new vibrating membrane system and a more
      concentrated formulation. These data will allow the design of a comparison in
      patients with CF.

PMID- 18613009
TI  - Analytical effectiveness calculations concerning the degradation of an inhibitive
      substrate by a steady-state biofilm.
AB  - A reaction engineering model for the degradation of an inhibitory substrate by a
      steady-state biofilm is presented. The model describes both the metabolic rate
      controlling behavior of this substrate in the biofilm and the effect of diffusion
      limitation caused by an arbitrary substrate on the active biofilm thickness. An
      analytical expression for the biocatalyst effectiveness factor is presented on
      the basis of Pirt kinetics for cell maintenance, first order substrate inhibition
      kinetics, and zero order substrate consumption kinetics. The proposed expression
      for the biocatalyst effectiveness factor is much more convenient to incorporate
      into a macroreactor model than the numerical alternatives. Simple criteria are
      presented to check the applicability of the model in case of true Monod kinetics.
      The analytical solution is expected to be particularly applicable to processes
      where a low soluble organic substrate controls the biomass growth, a situation
      which is often met in wastewater purification processes of industrial importance.
      The degradation of phenol by Pseudomonas sp. is treated as an example.

PMID- 18613010
TI  - Image analysis to quantify and measure UASB digester granules.
AB  - Two-dimensional image analysis was applied to counting, sizing, and density
      determinations of granules in full-scale and laboratory-scale upflow anaerobic
      sludge blanket (UASB) digesters. An advantage of this technique for monitoring
      laboratory-scale digester sludge is the small amount of material required for
      analysis. Quantification of number of granules using this method correlated well
      with dry weight determinations (r = 0.989). Distinguished granule size increased
      with time throughout the digestion process, supported by dry weight
      determinations which indicated an increase in biomass. The monitoring of granule
      density may reveal subtleties of the selection pressure placed on granules not
      noticed previously.

PMID- 18613011
TI  - Determination of cellular rate distributions in microbial cell populations:
      feeding rates of ciliated protozoa.
AB  - A novel procedure is proposed for determining distributions of rate properties
      and correlations of rate with state properties of microbial cell populations. The
      procedure is novel in that it uses transient data, and thus, it does not require
      that the population be in balanced growth, although it requires that the
      population structure does not change during the short transient experiment. The
      procedure is applied to populations of the ciliated protozoan Tetrahymena to
      determine ingestion rate variability. The number of ingested microspheres per
      cell and the single-cell protein content-an indicator of cell size-were directly
      determined with dual-color flow cytometry. The proposed technique revealed the
      correlation pattern of the particle ingestion rate with cell size. In particular,
      ingestion rate was found to be positively correlated with cell size for the
      smaller feeding cells and to be uncorrelated with size for the larger cells.
      Using the fact that particle uptake from dilute particle suspensions is a Poisson
      random process, we determined that the coefficient of variation of the
      distribution of ingestion rates within the feeding population is about 50%. It
      was concluded that the dynamics of particle ingestion can be accurately described
      only if it is realized that particle ingestion rates are distributed.

PMID- 18613012
TI  - Intracellular pH-based controlled cultivation of yeast cells: II. cultivation
      methodology.
AB  - Intracellular pH (pH(i)) was measured on-line in a bioreactor using a fluorescent
      pH(i) indicator, 9-aminoacridine, and controlled fed-batch cultivations of yeast
      cells based on pH(i) (FB-pH(i)) were performed. In FB-pH(i) cultivations,
      automated glucose additions were made to the culture in response to culture
      pH(i). The average ethanol (an-aerobic product) yield was significantly lower
      [0.12 g g(-1) glucose in fed-batch pH(i) cultivations with 100 ppm glucose
      additions (FB-pH(i)-100 cultivation) vs. 0.48 g g(-1) glucose in batch] and cell
      yield was higher (0.54 g g(-1) glucose in FB-pH(i)-100 cultivation vs. 0.3 g g(
      1) glucose in batch) compared to batch cultivation. An expression has been
      derived to calculate changes in pH(i) from measured fluorescence values when the
      cell concentration increases during growth. Cultivations based on pH(i),
      performed with different magnitudes of glucose addition (100, 50, and 10 ppm
      additions), showed that lower magnitudes of glucose addition resulted in lower
      ethanol yields while cell yield remained unaffected. The ratio of specific oxygen
      uptake rate to specific glucose uptake rate (OUR/GUR) increased with decreased in
      magnitude of glucose additions in FB-pH(i) cultivations, suggesting that the
      culture aerobic state was higher when the magnitude of glucose addition was
      lower. The average cell productivity in FB-pH(i) cultivations was 29% higher than
      in batch cultivation. Cells were also cultivated at high OUR conditions, and the
      results are compared with other cultivations.

PMID- 18613013
TI  - Gluco-oligosaccharide synthesis by free and immobilized beta-glucosidase.
AB  - Gluco-oligosaccharides were synthesized through the enzymatic condensation of D
      glucose at high concentration using a commercial almond beta-glucosidase. The
      synthesis reactions were carried out with both free and immobilized enzyme, with
      or without sorbitol, an efficient depressor of water activity (a(w)) in the
      presence of different glucose concentrations. The yield and the composition of
      the gluco-oligosaccharides produced changed with the reaction mixture and the
      form of the enzyme used (free or immobilized). The use of 5 M glucose solution
      permitted only disaccharides to be obtained, whereas with a glucose concentration
      of 7.5 M glucose, di-, tri-, and tetrasaccharides were produced. A 7.5 M glucose
      solution used with 4.4 M sorbitol gave three times more disaccharides than the
      same solution without sorbitol. Moreover, the immobilized enzyme was much more
      active in synthesis. The synthesis yield (oligomers mg/mL . mg of enzyme) after
      immobilization was 573% compared to that of the free enzyme, when a 7.5 M glucose
      solution was tested. The effects of substrate concentration, sorbitol addition
      and enzyme immobilization were investigated.

PMID- 18613014
TI  - Esterification of N-benzyloxycarbonyldipeptides in ethanol-water with immobilized
      papain.
AB  - The esterification of some N-benzyloxycarbonyl (Z)-dipeptides in ethanol
      containing water was investigated using papain as a catalyst. The esterification
      took place in ethanol containing a small amount of water (2% v/v, pH 9) with free
      papain at room temperature. The yield (after 24 h) of the ethyl ester was in the
      range of 25% to 50%. Any peptide bond cleavage of the substrates was not observed
      during esterification, indicating that the unfavorable amidase activity of papain
      was well depressed under these conditions. However, dipeptides having a D-amino
      amino acid (Z-valyl-D-alanine) or a bulky amino acid (Z-valylvaline) at the C
      terminal position could not be esterified. It was found that the immobilization
      of papain on Amberlite XAD-8 increased the yield of the ester significantly as
      compared with free papain. In the esterification of Z-valylalanine using
      immobilized papain, the optimum water content, pH of an added buffer, and
      temperature were found to be 2% (v/v), 9, and 40 degrees C, respectively. The
      water content affected the yield of the product ester significantly.

PMID- 18613015
TI  - Activated sludge process performance using a multistage tower aeration tank.
AB  - This study's objective was to clarify both experimentally and theoretically
      whether a vertical multistage tower aeration tank system is advantageous as
      compared with a completely mixed system, particularly with respect to
      purification efficiency, sludge settleability, and excess sludge production. In
      comparing the two systems: (1) purification efficiency in the multistage tower
      aeration system with partial fluid mixing with a large Peclet number was higher
      than in a corresponding completely mixed system for all applied organic loadings;
      (2) the multistage tower aeration system had some definite advantages with
      respect to sludge settleability and excess sludge production; (3) the activated
      sludge system's higher performance with partial fluid mixing was shown
      quantitatively with the axial dispersion model in conjunction with growth
      kinetics which involved rapid uptake such as biosorption and subsequent oxidative
      biodegradation processes of organic substances.

PMID- 18613016
TI  - Synthesis of fatty acid esters by a recombinant cutinase in reversed micelles.
AB  - Fusarium solani pisi recombinant cutinase, solubilized in AOT/isooctane-reversed
      micelles, was used to catalyze the esterification of fatty acids with aliphatic
      alcohols. Some relevant parameters for the enzyme activity such as pH, W(o)
      (water/surfactant molar ratio), temperature, and substrate concentration were
      optimized. Maximal specific activity was obtained for hexanol. The cutinase
      showed selectivity for short-chain fatty acids. The stability of the
      microencapsulated cutinase was investigated at various concentrations of water
      and different values of pH. Oleic acid had a negative effect on the cutinase
      stability, while hexanol proved to be a strong stabilizer increasing the half
      life of the enzyme about 45 times.

PMID- 18613017
TI  - Charged fusions for selective recovery of beta-galactosidase from cell extract
      using hollow fiber ion-exchange membrane adsorption.
AB  - We explored the use of charged fusions for selective recovery of beta
      galactosidase from cell extract using a low-cost, easily scaled, fast, charge
      based separation technique-ion exchange on hollow fiber ion-exchange membranes
      (HFIEMs). The additional charges carried by a series of anionic fusion tails
      allowed selective binding and release of beta-galactosidase from Escherichia coli
      cell extract using the HFIEM cartridge. The purification factors increased with
      fusion length. The beta-galactosidase was recovered in active form. For the
      longest fusion studied, more than sixfold enrichment in specific activity was
      attained. The specific activity of the recovered fraction is comparable with that
      of commercial wild-type beta-galactosidase and affinity-purified fusion protein.

PMID- 18613018
TI  - Production of tPA in recombinant CHO cells under oxygen-limited conditions.
AB  - Animal cell bioreactors are often limited by the oxygen supply. The reduction in
      oxygen consumption per cell that occurs under hypoxic conditions may be exploited
      as a method for increasing reactor capacity if additional glucose is provided to
      offset increased glycolytic activity. The effects of oxygen deprivation on
      recombinant tPA (tissue-type plasminogen activator) production were investigated
      using midexponential and slowly growing CHO cells. The specific oxygen
      consumption rate can be reduced by at least 50% (mild hypoxic conditions) without
      affecting the cell growth rate, maximum cell concentration, tPA production rate,
      or tPA quality (as characterized by the tPA-specific activity and SDS-PAGE
      analysis). This suggests that mild-hypoxic conditions (with sufficient glucose)
      can be used to double the cell concentration and volumetric tPA production rate
      (at a constant volumetric oxygen supply rate) without sacrificing product
      quality. However, anoxic conditions should be avoided. When slowly growing
      cultures were exposed to anoxia, the tPA production rate decreased by 80% without
      affecting tPA quality. However, when midexponential cultures were exposed to
      anoxia, the drop in tPA production was accompanied by a decrease in tPA quality
      that ranged from a 40% decrease in tPA specific activity to extensive tPA
      degradation.

PMID- 18613019
TI  - Microencapsulation selection for isolation of yeast mutants with increased
      secretion of Aspergillus awamori glucoamylase.
AB  - We have developed a microencapsulation selection method which allows the rapid
      and quantitative screening of >10(6) yeast cells for enhanced secretion of
      Aspergillus awamori glucoamylase. The method provides a 400-fold single-pass
      enrichment for high-secreting mutants, and can be straightforwardly adapted for
      application to growth-based selection schemes with other microorganisms and
      enzymes.

PMID- 18613020
TI  - A two-stage bioreactor system for the production of recombinant proteins using a
      genetically engineered baculovirus/insect cell system.
AB  - A two-stage bioreactor scheme was developed for the large-scale production of
      recombinant proteins using a genetically engineered baculovirus/insect cell
      system. The first bioreactor was employed for cell growth and the second for cell
      infection. Silkworm Bm5 cells were infected with a recombinant baculovirus,
      BmNPV/P5.cat, containing a bacterial chloramphenicol acetyltransferase (CAT) gene
      under the control of the polyhedrin gene promoter of Bombyx mori nuclear
      polyhedrosis virus (BmNPV). This recombinant baculovirus has been used as an
      expression vector for the production of recombinant CAT enzyme. A specific
      productivity of 82 to 90 microg CAT/(10(6) cells) was obtained using the
      BmNPV/Bm5 expression system, a yield similar to that achieved using the AcNPV/Sf
      expression system. Repeated infection of high-density cell cultures did not
      reduce the specific productivity of the CAT enzyme. Most importantly, the
      problems associated with the infection of high-density cell cultures were
      resolved by means of controlled infection conditions and appropriate
      replenishment of spent culture medium following infection. The glucose uptake
      rate by the cells following infection was 50% higher than that by the cells
      before infection. Not only did the infection of high-density cell cultures result
      in consistent yields of 250 mg/L of CAT enzyme, but also the two-stage bioreactor
      system was proven to be reliable for a long-term operation beyond 600 h.

PMID- 18613021
TI  - Kinetic models for synthesis by a thermophilic alcohol dehydrogenase.
AB  - Alcohol dehydrogenase (E. C. 1.1.1.1) from Thermoanaerobium brockii at 25 degrees
      C and at 65 degrees C is more active with secondary than primary alcohols. The
      enzyme utilizes NADP and NADPH as cosubstrates better than NAD and NADH. The
      maximum velocities (V(m)) for secondary alcohols at 65 degrees C are 10 to 100
      times higher than those at 25 degrees C, whereas the K(m) values are more
      comparable.At both 25 degrees C and 65 degrees C the substrate analogue
      1,1,1,3,3,3-hexafluoro-2-propanol inhibited the oxidation of alcohol
      competitively with respect to cyclopentanol, and uncompetitively with respect to
      NADP. Dimethylsulfoxide inhibited the reduction of cyclopentanone competitively
      with respect to cyclopentanone, and uncompetitively with respect to NADPH. As a
      product inhibitor, NADP was competitive with respect to NADPH. These results
      demonstrate that the enzyme binds the nucleotide and then the alcohol or ketone
      to form a ternary complex which is converted to a product ternary complex that
      releases product and nucleotide in that order.At 25 degrees C, all aldehydes and
      ketones examined inhibited the enzyme at concentrations above their Michaelis
      constants. The substrate inhibition by cyclopentanone was incomplete, and it was
      uncompetitive with respect to NADPH. Furthermore, cyclopentanone as a product
      inhibitor showed intercept-linear, slope-parabolic inhibition with respect to
      cyclopentanol. These results indicate that cyclopentanone binds to the enzyme
      NADP complex at high concentrations. The resulting ternary complex slowly
      dissociates NADP and cyclopentanone.At 65 degrees C, all of the secondary
      alcohols, with the exception of cyclohexanol, show substrate activation at high
      concentration. Experiments in which NADP was the variable substrate and
      cyclopentanol as the constant-variable substrate over a wide range of
      concentrations gave double reciprocal plots in which the intercepts showed
      substrate activation and the slopes showed substrate inhibition. These results
      indicate that the secondary alcohols bind to the enzyme-NADPH complex at high
      concentrations and that the resulting ternary complex dissociates NADPH faster
      than the enzyme-NADPH complex.

PMID- 18613022
TI  - Neural network modeling of batch cell growth pattern.
AB  - The capability of neural networks in modeling batch cell growth by providing
      initial conditions only is tested in this study. The neural network tested is of
      the back-propagation-type including a newly discovered saturation-type transfer
      function. The simulation and prediction results of this neural network modeling
      will be demonstrated.

PMID- 18613023
TI  - The molecular weight cut-off of microcapsules is determined by the reaction
      between alginate and polylysine.
AB  - Mammalian cells encapsulated in alginate-polylysine microcapsules are used as
      artificial organs in cancer research and in biotechnology. These applications
      require microcapsules with a reproducible mol. wt. cut-off. The high cost of the
      polycation, polylysine, requires an efficient preparation procedure. This article
      shows that the overall reported contact time of 5 minutes at ambient conditions
      should be increased several times in order to reach a maximal binding between the
      calcium alginate beads and 0.1% (w/v) polylysine solutions. An increase of the
      polylysine concentration from 0.0125% to 0.8% (w/v) resulted in a faster maximal
      binding, but the amount of polylysine bound increased also. Immersion of calcium
      alginate beads with a diameter of 750 mum, prepared from 1 mL alginate, in 30 mL
      of a 0.8% (w/v) polylysine solution, resulted in a polylysine spill of more than
      89%. The time required to reach a maximal binding was related to the reaction
      temperature. The interaction zone between calcium alginate beads and fluorescein
      isothiocyanate-labeled polylysine solutions was visualized with a confocal laser
      scanning microscope as a function of time. Microcapsules, prepared at 40 degrees
      C with 0.1% (w/v) polylysine solutions with mol. wts. between 12 and 249.2 kD,
      were permeable for fluorescein isothiocyanate-labeled dextran, mol. wt. 4.7, but
      not for 40.5 kD. Higher polylysine concentrations resulted in a membrane with a
      mol. wt. cut-off lower than 4.7 kD.

PMID- 18613024
TI  - A model system for a fluorometric biosensor using permeabilized Zymomonas mobilis
      or enzymes with protein confined dinucleotides.
AB  - Using permeabilized Zymomonas mobilis or glucose-fructose oxidoreductase isolated
      from this microorganism a model system for biosensors with a protein confined
      NADP(H) cofactor for the determination of glucose, fructose, gluconolactone, and
      sorbitol was developed. Either permeabilized microorganisms containing the
      oxidoreductase or the pure enzyme were confined via membrane separation in a
      small measuring chamber, that was integrated into a flow injection analysis
      system (FIA). The measuring principle was the monitoring of the NAD(P)H
      fluorescence, excited at 360 nm and measured at 450 nm. NADP(H), which is
      confined in the protein complex, was oxidized or reduced during the enzymatic
      reactions and the changes in the fluorescence intensity were related to the
      substrate concentration. The sensitivity of the system covered a range from 0.001
      to 100 g/L of the analyte depending on substrate and operating conditions. The
      applicability of this model system for bioprocess monitoring was proved using
      samples from a Pseudomonas pseudoflava cultivation.

PMID- 18613025
TI  - Immobilization of enzyme onto cellulose-titanium oxide composite fiber.
AB  - Fibers of a cellulose-TiO(2) composite were prepared by the reaction of cellulose
      with titanium iso-propoxide. Enzymes were immobilized on the fibers easily and
      simply under mild conditions. The fibers were stable in common solvents, high
      ionic solutions, and over a wide range of pH values 3-10.

PMID- 18613026
TI  - Bioconversion of lactose/whey to fructose diphosphate with recombinant
      saccharomyces cerevisiae cells.
AB  - Genetically engineered Saccharomyces cerevisiae strains that express Escherichia
      coli beta-galactosidase gene are able to bioconvert lactose or whey into fructose
      1,6-diphosphate (FDP). High FDP yields from whey were obtained with an
      appropriate ratio between cell concentration and inorganic phosphate. The biomass
      of transformed cells can be obtained from different carbon sources, according to
      the expression vector bearing the lacZ gene. We showed that whey can be used as
      the carbon source for S. cerevisiae growth and as the substrate for bioconversion
      to fructose diphosphate.

PMID- 18613027
TI  - Sequence length polymorphisms within primate amelogenin and amelogenin-like
      genes: usefulness in sex determination.
AB  - Sequence length polymorphisms between the amelogenin (AMELX) and the amelogenin
      like (AMELY) genes both within and between several mammalian species have been
      identified and utilized for sex determination, species identification, and to
      elucidate evolutionary relationships. Sex determination via polymerase chain
      reaction (PCR) assays of the AMELX and AMELY genes has been successful in greater
      apes, prosimians, and two species of old world monkeys. To date, no sex
      determination PCR assay using AMELX and AMELY has been developed for new world
      monkeys. In this study, we present partial AMELX and AMELY sequences for five old
      world monkey species (Mandrillus sphinx, Macaca nemestrina, Macaca fuscata,
      Macaca mulatta, and Macaca fascicularis) along with primer sets that can be used
      for sex determination of these five species. In addition, we compare the
      sequences we generated with other primate AMELX and AMELY sequences available on
      GenBank and discuss sequence length polymorphisms and their usefulness in sex
      determination within primates. The mandrill and four species of macaque all share
      two similar deletion regions with each other, the human, and the chimpanzee in
      the region sequenced. These two deletion regions are 176-181 and 8 nucleotides in
      length. In analyzing existing primate sequences on GenBank, we also discovered
      that a separate six-nucleotide polymorphism located approximately 300 nucleotides
      upstream of the 177 nucleotide polymorphism in sequences of humans and chimps was
      also present in two species of new world monkeys (Saimiri boliviensis and Saimiri
      sciureus). We designed primers that incorporate this polymorphism, creating the
      first AMELX and AMELY PCR primer set that has been used successfully to generate
      two bands in a new world monkey species.

PMID- 18613028
TI  - Simulated SEM images for resolution measurement.
AB  - Resolution is a key performance metric, which often defines the quality of a
      scanning electron microscope (SEM). Traditionally, there is the subjective
      measurement of the distance between two points on special "resolution" samples
      and there are several computer-based resolution-calculation methods. These
      computer-based resolution-calculation methods are much more precise than direct
      measurement, but none of them can currently be considered an objective way of
      measuring the resolution. The methods are still under development; therefore,
      objective testing is necessary. One approach to algorithm testing is to use
      simulated images. Simulated images are very useful for this purpose because they
      can be well-defined in all parameters unlike the real SEM images. Simulated
      images can be generated that closely mimic the gold-on-carbon SEM test sample
      images that usually consist of bright grains on a dark background. Simulation can
      account for edge effect, roughness of the substrate, different focusing, drift
      and vibration, and noise. Shapes, positions, and sizes of the grain structures
      are random. The simulated images can be then used for testing the resolution
      calculation methods, especially for finding how the particular properties of SEM
      images affect the resultant instrument performance and image resolution. To
      support this testing, NIST has developed and made available a reference set of
      simulated SEM images generated using the methods described in this article.

PMID- 18613031
TI  - Advances in the treatment of acute myeloid leukemia: from chromosomal aberrations
      to biologically targeted therapy.
AB  - We describe several recent advances in our understanding and treatment of acute
      myeloid leukemia (AML) and myelodysplastic syndrome (MDS) including the use of
      cytogenetics to classify these diseases and to identify therapies that are
      specific for the abnormalities. Cell lines have provided readily available and
      very relevant models to understand these diseases. The two clear successes
      include the use of retinoic acid for acute promyelocytic leukemia and tyrosine
      kinase inhibitors (e.g., imatinib) for chronic myelogenous leukemia. Very recent
      results suggest a particular activity of lenalidomide, an analogue of
      thalidomide, in MDS patients with deletions of the long arm of chromosome 5 (so
      called 5q minus syndrome), and notable activity of azanucleoside DNA
      demethylating agents in MDS with loss of chromosome 7. However, for the vast
      majority of cytogenetic abnormalities found in AML/MDS, no specific therapies
      have been identified. The use of a variety of molecular biology techniques have
      identified a large number of genomic abnormalities; the challenge of the next
      several decades is to identify specific therapies for these molecular defects.

PMID- 18613030
TI  - Oxysterol-induced osteogenic differentiation of marrow stromal cells is regulated
      by Dkk-1 inhibitable and PI3-kinase mediated signaling.
AB  - Osteoporosis and its complications cause morbidity and mortality in the aging
      population, and result from increased bone resorption by osteoclasts in parallel
      with decreased bone formation by osteoblasts. A widely accepted strategy for
      improving bone health is targeting osteoprogenitor cells in order to stimulate
      their osteogenic differentiation and bone forming properties through the use of
      osteoinductive/anabolic factors. We previously reported that specific naturally
      occurring oxysterols have potent osteoinductive properties, mediated in part
      through activation of hedgehog signaling in osteoprogenitor cells. In the present
      report, we further demonstrate the molecular mechanism(s) by which oxysterols
      induce osteogenesis. In addition to activating the hedgehog signaling pathway,
      oxysterol-induced osteogenic differentiation is mediated through a Wnt signaling
      related, Dkk-1-inhibitable mechanism. Bone marrow stromal cells (MSC) treated
      with oxysterols demonstrated increased expression of osteogenic differentiation
      markers, along with selective induced expression of Wnt target genes. These
      oxysterol effects, which occurred in the absence of beta-catenin accumulation or
      TCF/Lef activation, were inhibited by the hedgehog pathway inhibitor,
      cyclopamine, and/or by the Wnt pathway inhibitor, Dkk-1. Furthermore, the
      inhibitors of PI3-Kinase signaling, LY 294002 and wortmanin, inhibited oxysterol
      induced osteogenic differentiation and induction of Wnt signaling target genes.
      Finally, activators of canonical Wnt signaling, Wnt3a and Wnt1, inhibited
      spontaneous, oxysterol-, and Shh-induced osteogenic differentiation of bone
      marrow stromal cells, suggesting the involvement of a non-canonical Wnt pathway
      in pro-osteogenic differentiation events. Osteogenic oxysterols are, therefore,
      important small molecule modulators of critical signaling pathways in pluripotent
      mesenchymal cells that regulate numerous developmental and post-developmental
      processes.

PMID- 18613029
TI  - NF-kappaB, but not p38 MAP kinase, is required for TNF-alpha-induced expression
      of cell adhesion molecules in endothelial cells.
AB  - In response to inflammation stimuli, tumor necrosis factor-alpha (TNF-alpha)
      induces expression of cell adhesion molecules (CAMs) in endothelial cells (ECs).
      Studies have suggested that the nuclear factor-kappaB (NF-kappaB) and the p38 MAP
      kinase (p38) signaling pathways play central roles in this process, but
      conflicting results have been reported. The objective of this study is to
      determine the relative contributions of the two pathways to the effect of TNF
      alpha. Our initial data indicated that blockade of p38 activity by chemical
      inhibitor SB203580 (SB) at 10 microM moderately inhibited TNF-alpha-induced
      expression of three types of CAMs; ICAM-1, VCAM-1 and E-selectin, indicating that
      p38 may be involved in the process. However, subsequent analysis revealed that
      neither 1 microM SB that could completely inhibit p38 nor specific knockdown of
      p38alpha and p38beta with small interference RNA (siRNA) had an apparent effect,
      indicating that p38 activity is not essential for TNF-alpha-induced CAMs. The
      most definitive evidence to support this conclusion was from the experiments
      using cells differentiated from p38alpha knockout embryonic stem cells. We could
      show that deletion of p38alpha gene did not affect TNF-alpha-induced ICAM-1 and
      VCAM-1 expression when compared with wild-type cells. We further demonstrated
      that inhibition of NF-kappaB completely blocked TNF-alpha-induced expression of
      ICAM-1, VCAM-1 and E-selectin. Taken together, our results clearly demonstrate
      that NF-kappaB, but not p38, is critical for TNF-alpha-induced CAM expression.
      The inhibition of SB at 10 microM on TNF-alpha-induced ICAM-1, VCAM-1 and E
      selectin is likely due to the nonspecific effect of SB.

PMID- 18613032
TI  - Src transformation of colonic epithelial cells: enhanced anchorage-independent
      growth in an Apc(+/min) background.
AB  - Colon cancer arises through a multistep process involving inactivation of tumor
      suppressor proteins and activation of oncogene-encoded proteins. Development of
      colon cancer frequently involves mutation of the adenomatous polyposis coli (APC)
      tumor suppressor. The activity of the proto-oncogene-encoded Src tyrosine kinase
      is commonly elevated in colon cancer, with higher activity observed as tumors
      progress and metastasize. Both APC and Src are multifunctional proteins that have
      been implicated in the control of cell proliferation, but also as regulators of
      cytoskeletal changes associated with cell motility and invasion. To investigate
      the potential for biological cooperativity between APC partial loss-of-function
      and Src gain-of-function, oncogenic Src was stably expressed in mouse colon
      epithelial cell lines IMCE (APC(+/min)) and YAMC (APC(+/+)). Under permissive
      growth conditions, these lines are conditionally immortalized through
      inactivation of p53. Irrespective of the APC genotype or p53 status, oncogenic
      Src expression led to morphologic transformation associated with loss of cell
      cell junctions, cytoskeletal disorganization, and acquisition of invasive
      properties. However IMCE cells that carry one copy of the mutant APC(min) allele
      exhibited increased capacity for Src-mediated anchorage-independent proliferation
      as compared to the YAMC cells, and this property was enhanced under permissive
      growth conditions. beta-catenin levels and transcriptional activity were also
      elevated in the Src-transformed IMCE cells. The selective Src inhibitor, AZD0530,
      was found to be effective in blocking both cell invasion and anchorage
      independent proliferation. These findings suggest that the combined effects of
      elevated Src activity and APC partial loss-of-function may contribute to the
      growth of colon tumors.

PMID- 18613033
TI  - Pharmacokinetics of dexamethasone in a rat model of rheumatoid arthritis.
AB  - Dexamethasone (DEX) is often given for the treatment of rheumatoid arthritis and
      clinical dosing regimens of DEX have often been based empirically. This study
      tests whether the inflammation processes in a rat model of rheumatoid arthritis
      alters the clearance and volume of distribution of DEX when compared with healthy
      controls. Groups of healthy and arthritic male Lewis rats received either a low
      (0.225 mg/kg) or high (2.25 mg/kg) intramuscular dose of DEX. Arthritis was
      induced by intradermal injection of type II porcine collagen in incomplete
      Freund's adjuvant emulsion at the base of the tail. DEX was dosed in the
      arthritic animals 22 days post arthritis induction. Plasma DEX concentrations
      were determined by HPLC. Plasma concentration versus time data were analysed by
      non-compartmental analysis and pharmacokinetic model fitting using the population
      pharmacokinetic software NONMEM V. A linear bi-exponential pharmacokinetic model
      with extravascular input described the data for both healthy and arthritic
      animals. Clearance was the only parameter determined statistically different
      between both groups (healthy=1.05 l/h/kg, arthritic=1.19 l/h/kg). The steady
      state volume of distribution for both groups was 4.85 l/kg. The slight difference
      in clearance was visibly undetectable and unlikely to produce meaningful changes
      in DEX disposition in arthritic rats.

PMID- 18613034
TI  - NTP-CERHR expert panel report on the reproductive and developmental toxicity of
      bisphenol A.

PMID- 18613035
TI  - Effects of an outreach and internal navigation program on breast cancer diagnosis
      in an urban cancer center with a large African-American population.
AB  - BACKGROUND: Compared with white women, African-American (AA) women who are
      diagnosed with breast cancer experience an excess in mortality. To improve
      outcomes, the authors implemented community education and outreach initiatives in
      their cancer center, at affiliated primary care sites, and in the surrounding
      communities. They then assessed the effectiveness of these outreach initiatives
      and internal patient navigation on stage of diagnosis. METHODS: This cross
      sectional study was an analysis of all women with breast cancer who were
      diagnosed and/or treated in the years from 2001 through 2004. The outreach
      initiatives were implemented in 2001; 125 trained Community Health Advocates
      (CHAs) provided educational programs to the community, and Patient Navigators
      communicated directly with patients to encourage screening, diagnostic
      procedures, and treatment. RESULTS: In total, 487 patients were diagnosed/treated
      from 2001 through 2004. Since 2001, there were 1148 community interventions by
      CHAs with an estimated program attendance of >10,000 participants. In the
      interval from 2001 through 2004, the proportion of stage 0 (in situ) breast
      cancers increased from 12.4% (n = 14) to 25.8% (n = 33; P < .005), and there was
      a decline in stage IV invasive breast cancers from 16.8% (n = 19) to 9.4% (n =
      12; P < .05). CONCLUSIONS: The outreach initiatives and internal patient
      navigation appear to have improved stage at diagnosis. To determine whether
      specific patients presented earlier as a result of specific community outreach
      initiatives, prospective work is underway to measure the effects of these
      interventions on potential stage migration. Similarly, prospective data are being
      collected to determine whether Patient Navigators influence treatment and
      appointment adherence as well as the underlying reasons for barriers to specific
      interventions in this underserved minority population.

PMID- 18613036
TI  - Tissue-specific metabolic activation and mutagenicity of 3-nitrobenzanthrone in
      MutaMouse.
AB  - 3-Nitrobenzanthrone (3-NBA) is a mutagen and suspected human carcinogen detected
      in diesel exhaust, airborne particulate matter, and urban soil. We investigated
      the tissue specific mutagenicity of 3-NBA at the lacZ locus of transgenic
      MutaMouse following acute single dose or 28-day repeated-dose oral
      administration. In the acute high dose (50 mg/kg) exposure, increased lacZ mutant
      frequency was observed in bone marrow and colonic epithelium, but not in liver
      and bladder. In the repeated-dose study, a dose-dependent increase in lacZ mutant
      frequency was observed in bone marrow and liver (2- and 4-fold increase above
      control), but not in lung or intestinal epithelium. In addition, a concentration
      dependent increase in mutant frequency (8.5-fold above control) was observed for
      MutaMouse FE1 lung epithelial cells exposed in vitro. 1-Nitropyrene reductase, 3
      NBA reductase, and acetyltransferase activities were measured in a variety of
      MutaMouse specimens in an effort to link metabolic activation and mutagenicity.
      High 3-NBA nitroreductase activities were observed in lung, liver, colon and
      bladder, and detectable N-acetyltransferase activities were found in all tissues
      except bone marrow. The relatively high 3-NBA nitroreductase activity in
      MutaMouse tissues, as compared with those in Salmonella TA98 and TA100, suggests
      that 3-NBA is readily reduced and activated in vivo. High 3-NBA nitroreductase
      levels in liver and colon are consistent with the elevated lacZ mutant frequency
      values, and previously noted inductions of hepatic DNA adducts. Despite an
      absence of induced lacZ mutations, the highest 3-NBA reductase activity was
      detected in lung. Further studies are warranted, especially following inhalation
      or intratracheal exposures.

PMID- 18613037
TI  - In vitro evaluation of the clastogenicity of fumagillin.
AB  - Fumagillin, an antibiotic compound produced by Aspergillus fumigatus, is
      effective against microsporidia and various Amoeba species, but is also toxic
      when administered systemically to mammals. Furthermore, a recent in vivo study by
      Stanimirovic Z et al. 2007: (Mutat Res 628:1-10) indicated genotoxic effects of
      fumagillin. The aim of the present study was to investigate and explain the
      clastogenic effects of fumagillin (in the form of fumagillin dicyclohexylamine
      salt) on human peripheral blood lymphocytes in vitro by sister-chromatid
      exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests. The
      mitotic index (MI), proliferation index (PI), and nuclear division index (NDI)
      were calculated to evaluate the cytotoxic potential of fumagillin. Five
      concentrations of fumagillin (0.34, 0.68, 1.02, 3.07, and 9.20 microg/ml) were
      applied to lymphocyte cultures. All the tested concentrations of fumagillin
      increased the frequency of SCE per cell significantly (P < 0.001 or P < 0.01)
      compared with the negative control. A significant (P < 0.001) increase in
      frequency of structural CA was observed at the three highest concentrations in
      comparison with the negative control. In addition, the three highest test
      concentrations increased MN formation and decreased MI, PI, and NDI significantly
      compared with the negative control. The present results indicate that fumagillin
      is clastogenic and cytotoxic to cultured human lymphocytes.

PMID- 18613038
TI  - Optimization of yeast cell cycle analysis and morphological characterization by
      multispectral imaging flow cytometry.
AB  - Budding yeast Saccharoymyces cerevisiae is a powerful model system for analyzing
      eukaryotic cell cycle regulation. Yeast cell cycle analysis is typically
      performed by visual analysis or flow cytometry, and both have limitations in the
      scope and accuracy of data obtained. This study demonstrates how multispectral
      imaging flow cytometry (MIFC) provides precise quantitation of cell cycle
      distribution and morphological phenotypes of yeast cells in flow. Cell cycle
      analysis of wild-type yeast, nap1Delta, and yeast overexpressing NAP1, was
      performed visually, by flow cytometry and by MIFC. Quantitative morphological
      analysis employed measurements of cellular length, thickness, and aspect ratio in
      an algorithm to calculate a novel feature, bud length. MIFC demonstrated reliable
      quantification of the yeast cell cycle compared to morphological and flow
      cytometric analyses. By employing this technique, we observed both the G2/M delay
      and elongated buds previously described in the nap1Delta strain. Using MIFC, we
      demonstrate that overexpression of NAP1 causes elongated buds yet only a minor
      disruption in the cell cycle. The different effects of NAP1 expression level on
      cell cycle and morphology suggests that these phenotypes are independent. Unlike
      conventional yeast flow cytometry, MIFC generates complete cell cycle profiles
      and concurrently offers multiple parameters for morphological analysis.

PMID- 18613039
TI  - Analysis of flow cytometry data using an automatic processing tool.
AB  - In spite of recent advances in flow cytometry technology, most cytometry data is
      still analyzed manually which is labor-intensive for large datasets and prone to
      bias and inconsistency. We designed an automatic processing tool (APT) to rapidly
      and consistently define and describe cell populations across large datasets.
      Image processing, smoothing, and clustering algorithms were used to generate an
      expert system that automatically reproduces the functionality of commercial
      manual cytometry processing tools. The algorithms were developed using a dataset
      collected from CMV-infected infants and combined within a graphical user
      interface, to create the APT. The APT was used to identify regulatory T-cells in
      HIV-infected adults, based on expression of FOXP3. Results from the APT were
      compared directly with the manual analyses of five immunologists and showed close
      agreement, with a concordance correlation coefficient of 0.96 (95% CI 0.91-0.98).
      The APT was well accepted by users and able to process around 100 data files per
      hour. By applying consistent criteria to all data generated by a study, the APT
      can provide a level of objectivity that is difficult to match using conventional
      manual analysis.

PMID- 18613040
TI  - Development of respiratory structures in embryos and first and second instars of
      the bark scorpion, Centruroides gracilis (Scorpiones: Buthidae).
AB  - The SEM was used to study the development of respiratory structures in successive
      stages in relation to the overall changes occurring in the scorpions. Book lung
      development is a slow process, starting with spiracles and a sac-like atrium in
      the early embryo and continuing lamellar formation to 150 or more in the adult.
      In the embryo, the primordial epithelial cells become aligned in a planar pattern
      as they secrete granules of material that aggregate spontaneously to form the
      cuticular walls of the lamellae. A blade-like structure is formed consisting of
      cells sandwiched within the two cuticle walls they secreted. These cells are in
      the primordial air channel. The adjacent hemolymph channel is nearly devoid of
      cells, but cross-bridges develop and help stabilize the cuticle walls and
      maintain the width of the channel. The cells in the primordial air channel
      undergo cytolysis, leaving it open for air except for cuticular cross-bridges.
      Development continues in the newborn (first instars); the air channels of some
      lamellae still contain cells and are not yet functional for gas exchange. The
      first instars are weak and relatively inactive. They climb up on the mother's
      dorsum until the first molt (about 8 days). With the cuticular walls of the
      lamellae in place, cells adhering to the wall in the hemolymph channel produce a
      thin, new tissue layer (epithelium) on the lamellar wall facing the hemolymph
      channel. This layer has many discontinuities as though it is slowly developing.
      Formation of the tissue layer and cytolysis of the cells in the air channels
      continue through the first molt in which little book lung cuticle is shed as
      exuvium. The air channels of the second instars (foraging nymphs) are now cell
      free and open for air passage except for the cross-bridges. The tissue layer is
      still incomplete and continues to be formed. It may provide the hypodermal
      primordium for cuticle replacement in later molts, but development was not
      studied beyond the second instar except for comparison with book lungs in the
      adult. The blade-like lamellae in the adult are larger and more numerous than in
      the second instar, but in the anterior book lung the shape of the cuticle wall
      and cross-bridges and the widths of the air and hemolymph channels are about the
      same as in the second instar. The air channels in the posterior part of the
      lamellae have distinctive, vein-like space-holders. The similarity of the adult
      anterior lamellae with those in the second instar suggests retention of this part
      through the 4-5 molts to maturation, and/or cell processes like those in the
      embryo are repeated, but this needs to be examined in further studies of cell and
      cuticle changes before and during the molts.

PMID- 18613041
TI  - Trends in the clinical characteristics of the U.S. cystic fibrosis patient
      population from 1995 to 2005.
AB  - RATIONALE: Respiratory signs and symptoms (cough, sputum production, or crackles)
      are considered bellwethers of underlying cystic fibrosis (CF) lung disease. If
      respiratory signs and symptoms predict future lung function loss, then
      improvements in population lung function over the past decade should have been
      paralleled by a decrease in the prevalence of these variables in the same
      population. Additionally, changes in these variables over the past decade may
      provide insight into the improving health of the CF population. METHODS: Cross
      sectional data from the Epidemiologic Study of Cystic Fibrosis for each year
      between 1995 and 2005 were analyzed to characterize changes in pulmonary function
      and respiratory signs and symptoms over time. Patients were separated into five
      age groups: <6, 6-12, 13-17, 18-24, and >or=25 years. RESULTS: Serial cross
      sectional analyses of an average of 13,381 patients per year indicated that mean
      pulmonary function for the CF population improved and the percent of patients
      reporting cough or sputum production or having crackles or wheeze at their clinic
      visit decreased over the study period. Observed changes in pulmonary function
      were not consistently mirrored by changes in symptoms, which differed as a
      function of the variable studied and the age group. CONCLUSIONS: Reductions in
      respiratory signs and symptoms have paralleled improvements in pulmonary
      function. Both the absolute and relative magnitude of changes in prevalence for
      cough, sputum production, crackles, and wheeze differed among age groups and
      among variables. These results suggest the possibility that differences in
      respiratory signs and symptoms may arise from different underlying pathologies
      and may be influenced differently by therapeutic interventions.

PMID- 18613043
TI  - The cellulose-binding domain (CBD(Cex)) of an exoglucanase from Cellulomonas
      fimi: production in Escherichia coli and characterization of the polypeptide.
AB  - The gene fragment encoding the cellulose-binding domain (CBD) of an exoglucanase
      (Cex) from Cellulomonas fimi was subcloned and expressed in Escherichia coli.
      Transcription from the lac promoter coupled with translation from a consensus
      prokaryotic ribosome binding site led to the production of large quantities of
      CBD(Cex) (up to 25% total soluble cell protein). The polypeptide leaked into the
      culture supernatant (up to 50 mg . L(-1)), facilitating one-step purification by
      affinity chromatography on cellulose. The 11-kDa polypeptide reacted with Cex
      antiserum. Absence of free thiols indicated that the two Cys residues of CBD(Cex)
      form a disulfide bridge. It had the same N-terminal amino acid sequence as
      CBD(Cex) prepared from Cex by proteolysis, plus two additional N-terminal amino
      acid residues (Ala and Ser) encoded by the Nhel site introduced during plasmid
      construction. CBD(Cex) bound to a variety of beta-1, 4-glycans with different
      affinities and saturation levels. Adsorption to bacterial microcrystalline
      cellulose was dependent on the temperature, but not on the pH.

PMID- 18613044
TI  - Generation of a pH gradient in an immobilized enzyme system.
AB  - Several examples of two-step sequential reactions exist where, because of the
      poor equilibrium conversion by the first reaction, it is desirable to conduct the
      two reactions simultaneously. In such a scheme, the product of the first reaction
      is continuously removed by the second reaction, thus not allowing the first
      reaction to approach chemical equilibrium. Therefore, the first reaction is
      allowed to proceed in the desired direction at an appreciable rate. However, in
      many biochemical applications where enzyme catalysts are involved, the enzyme's
      activities are strong functions of pH. Where the pH optima of the first and
      second reaction differ by three to four units, the above reaction scheme would be
      difficult to implement. In these cases, the two reactions can be separated by a
      thin permeable membrane across which the desired pH gradient is maintained. In
      this article, it was shown, both by theory and experiment, that a thin, flat
      membrane of immobilized urease can accomplish this goal when one face of the
      membrane is exposed to the acidic bulk solution (pH(b) = 4.5) containing a small
      quantity of urea (0.01 M). In this particular case, the ammonia that was produced
      in the membrane consumed the incoming hydrogen ions and thus maintained the
      desired pH gradient. Experimental results indicate that with sufficient urease
      loading, the face of the membrane opposite to the bulk solution could be
      maintained at a pH that would allow many enzymes to realize their maximum
      activities ( approximately 7.5). It was also found that this pH gradient could be
      maintained even in the presence of a buffer, which greatly enhances the transport
      of protons into the membrane.

PMID- 18613045
TI  - Detection of bacterial contamination in cultures of eucaryotic cells by gas
      chromatography-mass spectrometry.
AB  - The use of gas chromatography-mass spectrometry for early detection of bacterial
      contaminations in cultures of baker's yeast, Penicillium chrysogenum, and an
      animal cell line was evaluated; muramic acid and characteristic cellular fatty
      acids were used as analytes. By analyzing branched-chain and cyclopropane
      substituted fatty acids as methyl esters, Staphylococcus epidermidis, Bacillus
      subtilis, Lactobacillus reuteri, Enterobacter cloacae, and Pseudomonas
      fluorescens were detected in a 500-fold excess (w/w) of baker's yeast; the
      amounts injected corresponded to 300 ng (dry mass) of the bacteria. Contamination
      with Bacillus was detected in cultures of Penicillium chrysogenum and animal
      cells by analyzing muramic acid, both as its alditol acetate derivative, using
      electron impact ionization, and its trifluoroacetyl methyl glycoside derivative,
      using negative ion-chemical ionization. The trifluoroacetylated derivative was
      detected in injected amounts corresponding to 1 x 10(3) bacterial cells in the
      contaminated animal cell line, whereas amounts corresponding to 1 x 10(5)
      bacteria were required for detection of the alditol acetate derivative; the
      amounts in the original samples were 5 x 10(5) and 5 x 10(6), respectively.
      However, the alditol acetate method exhibited lower chemical interferences than
      the trifluoroacetyl methyl glycoside procedure. The results show the potential of
      using gas chromatographic-mass spectrometric analysis of cellular constituents
      for the detection of bacterial contaminations in eucaryotic cultures as an
      alternative to conventional microbiological methods.

PMID- 18613046
TI  - Monoclonal antibody productivity and the metabolic pattern of perfusion cultures
      under varying oxygen tensions.
AB  - The metabolic pattern and cell culture kinetics of high-cell-density perfusion
      cultures were compared under two different oxygen transfer conditions: oxygen
      limiting and not limiting. When oxygen was a limiting factor during perfusion
      culture, both specific glucose uptake and lactate production rates increased,
      compared to non-oxygen-limited condition, by about 60% and 30%, respectively. The
      specific glutamine uptake rate under oxygen-limited conditions was almost 4.0
      times higher than that under non-oxygen-limited conditions. The activity of
      lactate dehydrogenase (LDH) released into the medium by the dead cells can be
      used as an indicator for the metabolic and physiological conditions related to
      oxygen limitation. There was a 3.2 times higher specific rate of LDH activity
      released by dead cells in oxygen-limited cultures than those in non-oxygen
      limited cultures. The specific production rate of monoclonal antibody was not
      significantly affected by the oxygen transfer conditions during the rapid cell
      growth period, but it rapidly increased toward the end of perfusion cultures. The
      higher perfusion rate may have limited further cell growth during high-cell
      density perfusion culture, because cell damage was caused by the hydrodynamic
      shear within a hollow fiber microfiltration cartridge installed to withdraw the
      spent medium and the waste metabolites.

PMID- 18613047
TI  - Transport of sugars via two anomer-specific sites on mannose-phosphotransferase
      system in Lactococcus cremoris: in vivo study of mechanism, kinetics, and
      adaptation.
AB  - Glucose uptake in Lactococcus lactis subsp. cremoris FD1 occurs via the mannose
      phosphotransferase system (Man-PTS), which is quite unspecific and allows
      transport of many different sugars and sugar analogues. It was previously shown
      (Benthin, S., Nielsen, J., Villadsen, J. Biotechnol. Bioeng. 40:137-146, 1992)
      that the kinetics of in vivo glucose uptake in a glucose-limited chemostat
      culture is best described by assuming that the glucose transport system has two
      anomer-specific sites with a relative uptake rate of 36% through the alpha-site.
      In the present study, the existence of anomer-specific sites on Man-PTS is shown
      by experiments where alpha-glucose, beta-glucose, mannose, and 2-deoxyglucose are
      added to glucose-limited chemostat cultures. A quantitative description of the
      competitive uptake of the involved sugars at the two sites is given. In a mannose
      limited chemostat culture, the relative glucose flux via the alpha-site is 50%,
      corresponding to a change toward the equilibrium composition of mannose (68%).
      Furthermore, when the feed to a mannose-limited chemostat culture is changed to
      glucose, the rate of change of relative glucose flux through the alpha-site
      corresponds to constitutive synthesis of Man-PTS with 36% alpha-site
      stoichiometry in new cells. When N-acetylglucosamine (73% alpha-anomer at
      equilibrium) is the limiting substrate, the relative glucose flux through the
      alpha-site is also 48% to 50%. With a feed of alpha-glucose generated
      enzymatically from nonmetabolizable sucrose the relative glucose flux through the
      alpha-site can be as high as 78%. Finally, growth in the presence of
      nonmetabolizable alpha-methylglucoside leads to formation of cells with a
      relative glucose flux through the alpha-site of 29% to 30%. The adaptation of the
      flux distribution between the alpha- and beta-site is tentatively explained by
      the hypothesis that two integral membrane proteins of Man-PTS are involved in
      this process.

PMID- 18613048
TI  - Alginate-chitosan coacervation in production of artificial seeds.
AB  - Survival of secondary embryoids of winter oilseed rape (Brassica napus ssp.
      oleifera cv. Primor) has been used as an assay for the development of artificial
      seeds involving complex coacervation of alginate (polyanion) with chitosan
      (polycation). Germination frequency of 100% was achieved for encapsulated
      embryoids when alginate formed the inner matrix and chitosan the outer layer.
      When the matrix makeup was reversed, there was no germination of embryoids. The
      artificial seeds produced were hardened in dilute alkaline solutions of NaOH and
      Ca(OH)(2). An optimum setting time could be selected based on a quantitative
      measurement of resistance of hardened capsules to compression and the germination
      frequency of the encapsulated embryoids.

PMID- 18613049
TI  - Stabilization of heterodimeric enzyme by multipoint covalent immobilization:
      Penicillin G acylase from Kluyvera citrophila.
AB  - We have developed a strategy for immobilization-stabilization of penicillin G
      acylase (PGA) from Kluyvera citrophila by controlled multipoint covalent
      attachment to agarose-aldehyde gels. This enzyme is composed by two dissimilar
      subunits noncovalently bound. Thus, in this article we establish clear
      correlations between enzyme stabilization and the multipoint immobilization
      and/or between enzyme stabilization and the involvement of the two subunits in
      the attachment of them to the support. We have demonstrated that important
      thermal stabilizations of derivatives were only obtained through a very intense
      enzyme-support multipoint attachment involving the whole enzyme molecule. In this
      way, we have prepared derivatives preserving more than 90% of catalytic activity
      and being more than 1000-fold more stable than soluble and one-point attached
      enzyme. In addition, the involvement of the two subunits in the covalent
      attachment to the support has proved to be essential to develop interesting
      strategies for reactivation of inactivated enzyme molecules [e.g., by refolding
      of immobilized PGA after previous unfolding with urea and sodium dodecyl sulfate
      (SDS)].

PMID- 18613050
TI  - Lipase catalyzed esterification of glycidol in organic solvents.
AB  - We studied the resolution of racemic glycidol through esterification with butyric
      acid catalyzed by porcine pancreatic lipase in organic media. A screening of
      seven solvents (log P values between 0.49 and 3.0, P being the n-octanol-water
      partition coefficient of the solvent) showed that neither log P nor the logarithm
      of the molar solubility of water in the solvent provides good correlations
      between enantioselectivity and the properties of the organic media. Chloroform
      was one of the best solvents as regards the enantiomeric purity (e. p.) of the
      ester produced. In this solvent, the optimum temperature for the reaction was
      determined to be 35 degrees C. The enzyme exhibited maximum activity at a water
      content of 13 +/- 2% (w/w). The enantiomeric purity obtained was 83 +/- 2% of (S)
      glycidyl butyrate and did not depend on the alcohol concentration or the enzyme
      water content for values of these parameters up to 200 mM and 25% (w/w),
      respectively. The reaction was found to follow a BiBi mechanism.

PMID- 18613051
TI  - A new approach for modeling cellulase-cellulose adsorption and the kinetics of
      the enzymatic hydrolysis of microcrystalline cellulose.
AB  - Two fractions of substrate in microcrystalline cellulose which differ in their
      adsorption capacities for the cellulases and their susceptibility to enzymatic
      attack have been identified. On the basis of a two-substrate hypothesis,
      mathematical models to describe enzyme adsorption and the kinetics of hydrolysis
      have been derived. A new nonequilibrium approach was chosen to predict cellulase
      cellulose adsorption. A maximum binding capacity of 76 mg protein per gram
      substrate and a half-maximum saturation constant of 26 filter paper units (FPU)
      per gram substrate have been calculated, and a linear relationship of hydrolysis
      rate vs. adsorbed protein has been found. The fraction of substrate more easily
      hydrolyzed, as calculated from hydrolysis data, represents 19% of the total
      effective substrate concentration. This fraction is only slightly different from
      that of other celluloses and has been estimated to be 27% and 30% for NaOH- and
      H(3)PO(4)-swollen cellulose, respectively. The effective substrate concentration
      is equal to the maximum amount of the substrate which can be converted during
      exhaustive hydrolysis. This in turn is determined by the overall degradability of
      the substrate by the cellulases (85-90% for microcrystalline cellulose) and by
      the cellobiose concentration during hydrolysis. The kinetic model is based on a
      summation of two integrated first-order reactions with respect to the effective
      substrate concentration. Furthermore, it includes the principal factors
      influencing the reaction rates: the ratio of filter paper and beta-glucosidase
      units per gram substrate and the initial substrate concentration. (

PMID- 18613052
TI  - Controlled release process to recover heterologous glycosylphosphatidylinositol
      membrane anchored proteins from CHO cells.
AB  - A semicontinuous process has been developed to recover heterologous proteins at
      increased concentrations and purities. Proteins attached to mammalian cell
      membranes by glycosylphosphatidylinositol (GPI) anchors can be selectively
      released into the supernatant by the enzyme phosphatidylinositol-phospholipase C
      (PI-PLC). Chinese hamster ovary (CHO) cells, genetically engineered to express
      the GPI anchored, human melanoma antigen (p97), were used as a model system.
      These cells were grown in protein containing growth medium. During a brief
      harvesting phase the medium was replaced by phosphate buffered saline (PBS)
      containing 10 mU/mL of PI-PLC and the GPI anchored protein was cleaved from the
      cell surface and recovered in soluble form at up to 30% purity. After harvesting,
      the cells were returned to growth medium where the protein was re-expressed
      within 40 h. The growth rate, viability, and protein production of cells,
      repeatedly harvested over a 44-day period, were not adversely affected. This
      continuous cyclic harvesting process allowed recovery of a heterologous protein
      at high purity and concentrations and could be applied to the recovery of other
      GPI anchored proteins and genetically engineered GPI anchored fusion proteins.

PMID- 18613053
TI  - Development of a recovery and recycle process for a pseudomonas lipase used for
      large-scale enzymatic synthesis.
AB  - Enzymes are potential catalysts for a wide range of large-scale chemical
      synthesis steps, particularly when the creation of a specific chiral center is
      desired. The efficient recycling of the enzyme catalyst and the removal of
      carryover impurities were crucial factors in the improvement of a stereoselective
      ester hydrolysis step used in the synthesis of a selective leukotriene
      antagonist. In this enzymatic reaction step, the substrate and product were both
      largely insoluble, while the enzyme was soluble in the aqueous reaction mixture.
      Microfiltration and ultrafiltration of the slurry reaction mother liquor
      indicated near 100% enzyme protein recovery, while activity recovery was about
      70% to 80%. These activity losses might be accounted for by enzyme degradation (1
      to 2 mg/L . h) during the 40-hour reaction period. Dissolved impurities,
      principally a diacid byproduct, in the enzyme recycling stream were reduced 60%
      to 70% by either lowering the solution pH to 4.0 or raising the solution ionic
      strength to 1 M.

PMID- 18613054
TI  - Immobilized Coffea arabica cell culture using a bubble-column reactor with
      controlled light intensity.
AB  - Coffea arabica cells immobilized by calcium alginate gel were photocultured using
      a bubble-column reactor under controlled light intensity. This process was
      carried out after their alkaloid productivity was improved by increasing the cell
      density in the initial gel matrix and preculturing the immobilized cells in the
      dark prior to light irradiation. The cells were grown in the form of a biofilm on
      gel beads, producing 100 mg/L of purine alkaloids in a 24-day batch culture.
      Alkaloid production was relatively constant with respect to light intensity
      changes, and also cell growth was not suppressed much at high light intensity,
      with these behaviors being different from those obtained using suspended cells.
      These phenomena are explained by estimating the light intensity gradient within
      the cell-immobilizing particles and by measuring the viable cell distribution
      within them. It subsequently suggests that the subsurface cells affect both the
      production and growth behaviors.

PMID- 18613055
TI  - Enhanced recovery of solavetivone from Agrobacterium transformed root cultures of
      Hyoscyamus muticus using integrated product extraction.
AB  - The integrated recovery of solavetivone from fungus elicited "hairy root"
      cultures of Hyoscyamus muticus is examined using volatile organic solvents and
      solid-phase adsorbents in an external loop extraction configuration. Hexane and
      pentane are shown to be toxic when added directly to the culture; however, growth
      of roots is not inhibited when cultures are exposed to media saturated with these
      hydrocarbons. Solid-phase neutral adsorbents, XAD-7 and XAD-16, display higher
      capacity and better solavetivone partitioning capability than the hydrocarbons;
      however, their selectivity for the sesquiterpene solavetivone is poor in
      comparison with hexane. In both cases, the integration of product recovery
      through extraction resulted in a doubling of product formation by alleviating
      feedback repression. Implications of these results to the recovery of secondary
      metabolites from plant root cultures are discussed. .

PMID- 18613056
TI  - A thermodynamically based correlation for maintenance gibbs energy requirements
      in aerobic and anaerobic chemotrophic growth.
AB  - A thermodynamic framework has been provided for the description of maintenance
      requirements of microorganisms. The central parameter is the biomass specific
      Gibbs energy consumption for maintenance, m(E) (kJ/C-mol biomass . h). A large
      set of data has been used including (i) a large range of different organisms
      (bacteria, yeasts, plant cells), (ii) mixed cultures, (iii) heterotrophic and
      autotrophic growth, (iv) growth under aerobic and anaerobic conditions, and (v) a
      large temperature range (5-75 degrees C). It appears that only the temperature
      has a major influence, with an energy of activation of 69 kJ/mol. Different
      electron donors or electron acceptors only show a very minor influence on m(E).
      On the basis of the data set, temperature correlations of m(E) have been derived
      for aerobic and anaerobic growth. The generalized concept for maintenance Gibbs
      energy is used to establish a correlation which allows the estimation of the
      biomass yield on electron donor as a function of C-source, electron donor,
      electron acceptor, N source, growth rate, and temperature. The advantage of using
      the m(E) parameter over other maintenance-related parameters (like mu(e), m(O2),
      m(D), gamma(D)m(D)) is discussed.

PMID- 18613057
TI  - Plant cell suspension culture rheology.
AB  - The results of rheological measurements on 10 different plant cell suspension
      cultures are presented. Nicotiana tabacum (tobacco) suspension cultures grown in
      serial batch subculture display high viscosity and power law rheology. This
      "undesirable" rheology is shown to be a result of elongated cell morphology. The
      rheology of Papaver somniferum (poppy) cell suspensions is quite different; poppy
      suspensions behave as Newtonian fluids and have relatively low viscosity (less
      than 15 cP) at fresh cell densities up to 250 g/L. This flow behavior can be
      attributed to a lack of elongation in batch-grown poppy cells. A simple
      correlation for the viscosity as a function of cell density is developed for
      poppy suspensions up to 300 g fresh weight (FW)/L. It is shown that tobacco cells
      do not elongate when grown in semicontinuous culture (daily media replacement).
      These semicontinuously cultured cells have rheological behavior that is
      indistinguishable from that of poppy, further confirming the dependence of
      rheology on plant cell morphology. The rheology of a wide variety of other plant
      suspensions at 200 g FW/L is presented. Most cell suspensions, including soybean,
      cotton, bindweed, and potato, display low viscosities similar to poppy
      suspensions. Only carrot and atriplex exhibit slight pseudoplastic behavior which
      corresponded to a slight degree of cellular elongation for these cultures. This
      demonstrates that complex rheology associated with elongated cell morphology is
      much less common than low-viscosity Newtonian behavior. High viscosity in plant
      cell culture is therefore not an intrinsic characteristic of plant cells but,
      instead, is a result of the ability to grow cultures to extremely high cell
      densities due to low biological oxygen demand.

PMID- 18613058
TI  - Extractive separation of penicillin G by facilitated transport via carrier
      supported liquid membranes.
AB  - The facilitated transport of penicillin G (Pen G), through a supported liquid
      membrane with Amberlite LA-2 dissolved in 1-decanol, supported on a microporous
      polypropylene membrane, were studied. The distribution coefficient was obtained
      from a batch extraction experiment. The effects of flow rate, carrier
      concentration, initial concentration of Pen G, and the pH of feed and stripping
      phases on the transport rate of Pen G through the supported liquid membrane were
      also investigated. The results are in agreement with theoretical predictions, and
      it is demonstrated that the transport of Pen G through the supported liquid
      membrane is controlled simultaneously by mass transfer across both aqueous and
      liquid membranes.

PMID- 18613059
TI  - Electric prompting and control of denitrification.
AB  - The effectiveness of a denitrification process which is driven and controlled by
      an electric current is demonstrated. Denitrifying microorganisms were immobilized
      on a carbon electrode and hydrogen was produced through the electrolysis of
      water. The hydrogen was utilized for the reduction of nitrate to N(2). The
      denitrification rate was a linear function of the electric current, and it was
      shown that about 1 mol of electron reduces 0.2 mol of nitrate to N(2) gas. These
      results exhibit that the proposed process is simple and feasible, especially for
      the treatment of low-strength nitrate solutions.

PMID- 18613060
TI  - Microbial utilization of levoglucosan in wood pyrolysate as a carbon and energy
      source.
AB  - The Waterloo Fast Pyrolysis Process (WFPP) can produce an organic liquid high in
      levoglucosan (1, 6-anhydro-beta-D-glucopyranose) content from suitably pretreated
      lignocellulosics. A variety of fungi and yeasts were screened for their ability
      to utilize and ferment this organic liquid. To enhance its fermentability, the
      pyrolysis tar was posttreated in three different ways: (1) an aqueous extract
      (lignin removed); (2) activated charcoal treated (lignin and aromatics removed);
      and (3) acid hydrolysate (lignin and aromatics removed with the levoglucosan
      hydrolyzed to glucose). Four fungal strains were examined. None grew in the
      aqueous extract, but all grew equally well in both the activated charcoal treated
      and the acid hydrolysate, suggesting that the aromatic species were inhibitory to
      growth. Seven yeast species were examined, two of which did not grow on any of
      the extracts. Five of the yeast strains grew well on both the aqueous extract as
      well as the activated charcoal extract. The hydrolysate was optimal in terms of
      biomass yield and ethanol production. Ethanol yields on the hydrolysate were
      comparable or better than those on glucose. Ethanol was also produced in the
      aqueous extract and activated charcoal-treated substrate, but yields were
      considerably lower than on the hydrolysate or glucose. It is apparent that a wood
      pyrolysate maximized for levoglucosan can serve as a fermentable substrate,
      although postpyrolysis clean-up appears necessary.

PMID- 18613061
TI  - On-line monitoring of cell concentration of Perilla frutescens in a bioreactor.
AB  - This article demonstrates the successful in situ real-time monitoring of the cell
      concentration of Perilla frutescens in a bioreactor by using a laser
      turbidimeter. It was found that turbidity measurements at 780 nm with the laser
      sensor were hardly affected by the red color of the anthocyanin produced by P.
      frutescens cells, nor by the aeration rate or agitation speed within the ranges
      investigated. There was an excellent linear relationship, with a correlation
      coefficient (r(2)) higher than 0.99, between the sensor's response and the cell
      concentration. The whole growth stage of the cells, i.e., lag, logarithmic, and
      stationary phases, in bioreactor cultivations, could be satisfactorily estimated
      on-line by means of the in situ turbidimeter. However, during the declining phase
      of the cells, an apparent deviation was observed between the on-line estimations
      and off-line measurements of cell concentrations by dry cell weight, while the
      wet cell weight could be estimated by the same turbidimeter system. We found that
      this deviation was caused by a decrease in the cell density due to an increase of
      the individual cell volume and a decrease of the cell dry weight during the
      declining phase.

PMID- 18613064
TI  - Mixed extracellular matrix ligands synergistically modulate integrin adhesion and
      signaling.
AB  - Cell adhesion to extracellular matrix (ECM) components through cell-surface
      integrin receptors is essential to the formation, maintenance and repair of
      numerous tissues, and therefore represents a central theme in the design of
      bioactive materials that successfully interface with the body. While the adhesive
      responses associated with a single ligand have been extensively analyzed, the
      effects of multiple integrin subtypes binding to multivalent ECM signals remain
      poorly understood. In the present study, we generated a high throughput platform
      of non-adhesive surfaces presenting well-defined, independent densities of two
      integrin-specific engineered ligands for the type I collagen (COL-I) receptor
      alpha(2)beta(1) and the fibronectin (FN) receptor alpha(5)beta(1) to evaluate the
      effects of integrin cross-talk on adhesive responses. Engineered surfaces
      displayed ligand density-dependent adhesive effects, and mixed ligand surfaces
      significantly enhanced cell adhesion strength and focal adhesion assembly
      compared to single FN and COL-I ligand surfaces. Moreover, surfaces presenting
      mixed COL-I/FN ligands synergistically enhanced FAK activation compared to the
      single ligand substrates. The enhanced adhesive activities of the mixed ligand
      surfaces also promoted elevated proliferation rates. Our results demonstrate
      interplay between multivalent ECM ligands in adhesive responses and downstream
      cellular signaling.

PMID- 18613065
TI  - Investigating the optical properties of dislocations by scanning transmission
      electron microscopy.
AB  - The scanning transmission electron microscope (STEM) allows collection of a
      number of simultaneous signals, such as cathodoluminescence (CL), transmitted
      electron intensity and spectroscopic information from individual localized
      defects. This review traces the development of CL and atomic resolution imaging
      from their early inception through to the possibilities that exist today for
      achieving a true atomic-scale understanding of the optical properties of
      individual dislocations cores. This review is dedicated to Professor David Holt,
      a pioneer in this field.

PMID- 18613066
TI  - Factors influencing diabetes self-management in Chinese people with type 2
      diabetes.
AB  - Patients with diabetes must incorporate a complicated regimen of self-management
      into their daily lives (e.g., taking medication, diet, exercise). Diabetes self
      management (DSM) is the cornerstone for controlling diabetes and preventing
      diabetic complications. The purpose of this study was to test a model describing
      the effects of individual and environmental factors on DSM in a sample of
      patients with diabetes in Beijing, China. Survey data were gathered from a
      convenience sample of 201 Chinese adults with type 2 diabetes during outpatient
      visits. Data were analyzed using structural equation modeling. Model fit indices
      indicated a good fit to the data. In the final model, belief in treatment
      effectiveness and diabetes self-efficacy were proximate factors affecting DSM.
      Knowledge, social support, and provider-patient communication affected self
      management indirectly via beliefs and self-efficacy. The findings provide a
      theoretical basis to direct the development of interventions for improving DSM in
      Chinese individuals with diabetes.

PMID- 18613067
TI  - Hitting the bull's eye rather than shooting yourself between the eyes.

PMID- 18613068
TI  - Does alpha-effect exist in E2 reactions? A G2(+) investigation.
AB  - The gas-phase base-induced bimolecular elimination (E2) reactions at saturated
      carbon with 13 bases, B(-) + CH3CH2Cl --> BH + CH2=CH2 + Cl(-) (B = HO, CH3O,
      CH3CH2O, FCH2CH2O, ClCH2CH2O, Cl, Br, FO, ClO, BrO, HOO, HSO, and H2NO), were
      investigated with the high-level G2(+) theory. It was found that all alpha-bases
      with adjacent lone pair electrons examined exhibited downward deviations from the
      correlation line between the overall barriers and proton affinities for the
      normal bases without adjacent lone pair electrons, indicating the existence of
      the alpha-effect in the gas phase E2 reactions. The sizes of the alpha-effect for
      the E2 reaction, DeltaH(alpha)(E2), span a smaller range if the alpha-atoms are
      on the same column in the periodic table, in contrast to the corresponding S(N)2
      reactions, where the DeltaH(alpha)(S(N)2) values significantly decrease from an
      upper to a lower column. The origin of the alpha-effects in E2 reactions can be
      interpreted by the favorable orbital interaction between the lone-pair electrons
      and positively charged anti-bonding orbital. It is worth noticing that the
      neighboring electron-rich pi lobe instead of lone pair electrons could also cause
      the alpha-effect in E2 reaction.

PMID- 18613069
TI  - Neutral hydrolyses of carbon disulfide: An ab initio study of water catalysis.
AB  - The water-catalyzed hydrolysis reaction of carbon disulfide (CS(2)) has been
      investigated at the levels of HF and MP2 with the basis set of 6-311++G(d,p)
      using the combined supramolecular/continuum models, in which up to six water
      molecules are involved in the hydrolysis and the effect of water bulk solvent is
      taken into account according to the polarizable continuum model (PCM). The
      activation Gibbs free energies in water solution, DeltaG(sol) (not equal) (298
      K), for the rate-determining steps of one up to six water hydrolyses are 247.9,
      184.2, 152.3, 141.8, 134.4, and 118.9 kJ/mol, respectively. The most favorable
      hydrolysis path of CS(2) involves a sort of eight-membered ring transition
      structure formed by six water molecules, among which three water molecules are
      not involved in the proton transfer, two near to the nonreactive sulfur atom, and
      one below the parent carbon disulfide. This suggests that the hydrolysis of CS(2)
      can be mediated with the water molecule(s) and be significantly facilitated by
      the cooperative effects of the water molecule(s) in the nonreactive region. The
      catalytic effects of water molecule(s) due to the alleviation of ring strain in
      the proton transfer process may result from the synergistic effects of
      rehybridization and charge reorganization from the prereaction complex to the
      rate-determining transition state structure induced by water molecule(s). PCM
      solvation models could significantly lower the rate-determining activation Gibbs
      free energies by 20-38 kJ/mol when two up to six explicit water molecules
      involved in the neutral hydrolysis of CS(2).

PMID- 18613070
TI  - Thermodynamics of single strand DNA base stacking.
AB  - The thermodynamics of the stacking to unstacking transitions of 24 single
      stranded DNA sequences (ssDNA), 10-12 bases in length, in sodium phosphate buffer
      were determined from 10 to 95 degrees C, using differential scanning calorimetry
      (DSC). An additional 22 ssDNA sequences did not exhibit an S<=>U transition in
      this temperature range. The transition properties of the ssDNA sequences with
      <or=60% self-complementarily in the reverse direction were independent of
      concentration with transition temperatures ranging from 15 to 70 degrees C, van't
      Hoff transition enthalpies from 92 to 201 kJ mol(-1) and transition enthalpies
      from 5 to 75% of the corresponding van't Hoff transition enthalpies. Since all
      the 16 doublets and 60 of the 64 triplets are present in both the transition and
      the non-transition ssDNA sequences, it is unlikely that the nucleation subset
      initiating stacking of the sequence is a specific doublet or triplet subset. Of
      the 141 quadruplet subsets of the 46 sequences, each transition ssDNA sequence
      contained at least one or more quadruplets not found in the non-transition ssDNA
      sequences. It could be concluded that the thermal stability of the stacked
      conformation was dependent on the presence of a possible nucleation quadruplet
      and the length of the ssDNA sequence and not on the G or C content of the ssDNA
      sequence, nor on the number of purine bases in the sequence.

PMID- 18613071
TI  - Fragment-based quantitative structure-activity relationship (FB-QSAR) for
      fragment-based drug design.
AB  - In cooperation with the fragment-based design a new drug design method, the so
      called "fragment-based quantitative structure-activity relationship" (FB-QSAR) is
      proposed. The essence of the new method is that the molecular framework in a
      family of drug candidates are divided into several fragments according to their
      substitutes being investigated. The bioactivities of molecules are correlated
      with the physicochemical properties of the molecular fragments through two sets
      of coefficients in the linear free energy equations. One coefficient set is for
      the physicochemical properties and the other for the weight factors of the
      molecular fragments. Meanwhile, an iterative double least square (IDLS) technique
      is developed to solve the two sets of coefficients in a training data set
      alternately and iteratively. The IDLS technique is a feedback procedure with
      machine learning ability. The standard Two-dimensional quantitative structure
      activity relationship (2D-QSAR) is a special case, in the FB-QSAR, when the whole
      molecule is treated as one entity. The FB-QSAR approach can remarkably enhance
      the predictive power and provide more structural insights into rational drug
      design. As an example, the FB-QSAR is applied to build a predictive model of
      neuraminidase inhibitors for drug development against H5N1 influenza virus.

PMID- 18613072
TI  - Pattern of tumor recurrence in initially nonmetastatic breast cancer patients:
      distribution and frequency of metastases at unusual sites.
AB  - BACKGROUND: Breast cancer is likely to have systemic involvement. However, to the
      authors' knowledge there are few reports to date regarding clinically detected
      patterns of metastasis, meticulously studied in regard to the natural history of
      breast cancer, including unusual sites of metastasis. METHODS: Patients treated
      for invasive breast cancer from April 1983 to May 2007 were retrospectively
      analyzed. Patterns of clinically apparent tumor recurrence, focusing especially
      on unusual metastases, were studied as well as possible risk factors for unusual
      metastases and their influence on survival. RESULTS: Overall, 3783 patients were
      eligible for the current analysis. The median duration of follow-up was 5.0 years
      (range, 0.6 years-20.4 years). Cumulative 5-year and 10-year survival rates were
      89.7% and 81.5%, respectively. "Unusual metastasis" was defined as systemic
      failure with a frequency of < or =1%; in the current series; it was observed in
      85 (2.2%) patients %. Of those, 70 (82%) had preceding metastasis in the usual
      sites. The median duration until the development of usual and unusual metastasis
      was 2.3 years and 3.6 years, respectively (P < .0001). Among 764 patients with
      distant metastasis, the 5-year cumulative overall survival rate in those with or
      without unusual metastasis was 53.5% and 53.4 years, respectively (P = .33). No
      risk factors for unusual metastasis were identified. CONCLUSIONS: This
      retrospective study examined the frequency of unusual metastases in a large
      number of Japanese patients with initially nonmetastatic breast cancer. The
      prognosis of patients with unusual metastases was found to be similar to that of
      patients with metastasis only at more usual sites.

PMID- 18613073
TI  - Modern humans are not (quite) isometric.
AB  - Allometric relationships are important sources of information for many types of
      anthropological and biological research. The baseline for all allometric
      relationships is isometry (or geometric similarity), the principal that shape is
      invariant of size. Here, we formally test for geometric similarity in modern
      humans, looking at the maximum lengths of four long bones (humerus, radius,
      femur, and tibia). We use Jolicoeur's multivariate allometry method to examine
      globally distributed samples of human populations, both collectively and
      individually. Results indicate that humans are not geometrically similar,
      although morphological deviations from isometry are small.

PMID- 18613074
TI  - Parotid cancer: Impact of changes from the 1997 to the 2002 American Joint
      Committee on Cancer classification on outcome prediction.
AB  - BACKGROUND: The TNM classification [American Joint Committee on Cancer (AJCC)] of
      salivary gland cancer was revised again in 2002. In the present study, the
      outcome prediction of the new TNM system was compared with the old 1997 TNM
      system in 202 patients with primary parotid cancer. METHODS: All patients treated
      from 1986 to 2006 were reclassified in both TNM systems. Disease-free survival
      (DFS) rates were calculated. The prognostic validity of both the TNM system and
      other factors were analyzed univariately (log-rank test) and multivariately (Cox
      regression). RESULTS: AJCC TNM stage changes from 1997 to 2002 altered the
      disease staging in 35% of the patients. Concerning DFS, the new TNM 2002 staging
      allowed significantly better separation of stage III, but not of stage I versus
      stage II. The TNM 2002 staging was the most powerful predictor for DFS according
      to multivariate analysis. The 1997 system showed no independent significance. The
      subclassification of the new stage IV was not satisfactory; no clear distinction
      of IVA versus III, and IVA versus IVB was possible. CONCLUSIONS: The TNM 2002
      staging is more valid than the 1997 system, but a significant problem was
      observed in separating stage I from stage II, and within the stage IV subgroups.

PMID- 18613076
TI  - The yield equations in the modeling and control of bioprocesses.
AB  - Two basic questions in bioprocess modeling are how many rate equations must be
      specified and which processes (substrate uptake, product formation, etc.) they
      should describe. The number of rate equations is constrained by the yield
      equations, which represent the balances of reducing power, energy in the form of
      ATP, and the various elements involved in microbial metabolism. These balances
      are derived from a simplified picture that divides metabolism into catabolic,
      anabolic, respiratory, and product formation pathways. The linear growth equation
      for aerobic metabolism and the Ludeking-Piret equation for product formation by
      fermentation are derived from these balances, and the yield coefficients are
      related to the metabolic parameters, Y(ATP) (P/O), etc. The use of oxygen for
      purposes other than respiration is included in the analysis and extends the idea
      of a constant "yield on available electrons" to very reduced substrates. These
      balances specify the number of degrees of freedom, i.e., the number of pieces of
      information required to complete the description of the system. This information
      may be in the form of measurements, knowledge of the biochemical pathways, or
      rate equations. The number of rate measurements available (usually two, the
      consumption rates of O(2) and CO(2)) versus the number needed defines the state
      estimation problem in bioprocess control. Rate equations usually specify the
      biomass growth rate, but it may be preferable to specify the specific consumption
      rate of the limiting nutrient.

PMID- 18613077
TI  - Use of a simple mathematical model to predict the behavior of Escherichia coli
      overproducing beta-lactamase within continuous single- and two-stage reactor
      systems.
AB  - A simple mathematical model is developed to help explain the complex population
      dynamics of an Escherichia coli host-plasmid expression/excretion system for beta
      lactamase within single- and two-stage reactors. The model successfully
      integrates the individual regulatory (tac promoter induction), genetic (runaway
      plasmid replication), and population dynamics (culture instability) aspects of
      the system. The model predicts, and experiment confirms, that high-level beta
      lactamase production and excretion cannot be easily maintained in single-stage
      reactors using the current plasmid construction. Stable target protein production
      and excretion is mathematically predicted, and experimentally confirmed, within
      two-stage reactors. The model is used to provide insight into engineering a more
      stable host-vector expression/excretion system for use in single-stage reactors.

PMID- 18613078
TI  - A fractal model for the characterization of mycelial morphology.
AB  - A new technique based on a fractal model has been developed for the
      quantification of the macroscopic morophology of mycelia. The morphological
      structuring is treated as a fractal object, and the fractal dimension, determined
      by an ultrasonic scattering procedure developed for the purpose, serves as a
      quantitative morphological index. Experimental observations reported earlier and
      simulations of mycelial growth, carried out using a probabilistic-geometric
      growth model developed for the purpose, both validate the applicability of the
      fractal model. In experiments with three different species, the fractal
      dimensions of pelletous structures were found to be in the range 1.45-2.0 and
      those of filamentous structures were in the range 1.9-2.7, with values around 2.0
      representing mixed morphologies. Fractal dimensions calculated from simulated
      mycelia are in rough agreement with these ranges. The fractal dimension is also
      found to be relatively insensitive to the biomass concentration, as seen by
      dilution of the original broths. The relation between morphology and filtration
      properties of the broths has also been studied. The fractal dimension shows a
      strong correlation with the index of cake compressibility and with the Kozeny
      constant, two filtration parameters that are known to be morphology dependent.
      This technique could thus be used to develop correlations between the morphology,
      represented by the fractal dimension, and important morphology-dependent process
      variables.

PMID- 18613079
TI  - Optimization of hepatocyte attachment to microcarriers: Importance of oxygen.
AB  - Many potential applications of primary hepatocytes cultured on microcarriers,
      such as an artificial liver or hepatocyte transplantation, would benefit from
      having a large number of hepatocytes attached to each microcarrier. In addition,
      the supply of primary hepatocytes is usually limited, so the efficient
      utilization of hepatocytes during attachment to microcarriers is necessary.
      Several physical parameters involved in the attachment process have been
      investigated, and the number of cells attached per microcarrier and the fraction
      of hepatocytes which attach have been quantitatively monitored. Variation of the
      partial pressure of gas phase oxygen in the incubation flask produced significant
      effects on the attachment of hepatocytes to microcarriers, with higher partial
      pressures of oxygen found to be necessary for attachment. In addition, variation
      of fluid depth and cell number, both of which influence the partial pressure of
      oxygen at the cell surface, affected hepatocyte attachment. The partial pressure
      of oxygen at the cell surface as a function of the physical parameters was
      analyzed using a simple one-dimensional theoretical model. Variations in the cell
      to-microcarrier ratio used for incubation indicate that a compromise must be made
      in terms of maximizing the number of cells per microcarrier and the fraction of
      total hepatocytes which attach. The maximum number of hepatocytes per
      microcarrier obtained in this work was approximately 100. The best attachment
      fraction, defined as the ratio of the number of hepatocytes attached to the total
      number added to the incubation, was approximately 90%.

PMID- 18613080
TI  - Microbial degradation of quinoline: Kinetic studies with Comamonas acidovorans
      DSM 6426.
AB  - The microbial degradation of quinoline by Comamonas acidovorans was studied in a
      laboratory scale stirred tank reactor. In continuous culture experiments using
      quinoline as a sole source of carbon and nitrogen, it was shown by means of mass
      balances that quinoline was converted completely to biomass, carbon dioxide, and
      ammonia. Degradation rates up to 0.7 g/L h were obtained. Measured yield
      coefficients Y(x/s) for quinoline were about 0.7 g/g, which is in agreement with
      the theoretical value for complete mineralization. Kinetic constants based on
      Haldane substrate inhibition were evaluated. The values were micro(max) = 0.48 h(
      1), K(i) = 69 mg/L, and K(s) < 1.45 mg/L.

PMID- 18613081
TI  - Partitioning behavior and enrichment of proteins with reversed micellar
      extraction: I. forward extraction of proteins from aqueous to reversed micellar
      phase.
AB  - Protein extractions using aerosol OT (AOT)-isooctane reverse micelle solutions
      have been studied to explore the potential for separating and enriching proteins
      with the reversed micellar extraction. The effects of pH, ionic strength, and
      different cations of chlorides in a bulk aqueous phase and of AOT concentration
      in an organic phase on the partitioning of lysozyme and myoglobin and the
      solubilization of water are presented in detail. The extraction of lysozyme was
      affected by the concentration of potassium or barium but was almost independent
      of that of sodium or calcium, whose ionic diameter is smaller than that of
      potassium and barium. For the extraction of myoglobin, however, the effect of
      barium concentration was not appreciable. Lysozyme could be enriched into the
      reversed micellar phase up to 30 times the aqueous feed concentration.

PMID- 18613082
TI  - Substantial overproduction of antibodies by applying osmotic pressure and sodium
      butyrate.
AB  - Much of the current cell technology has enabled increased antibody production
      levels due to judicious nutrient feeding to raise cell densities and design
      better bioreactors. This study demonstrates that hybridomas can be
      hyperstimulated to produce higher immunoglobulin (lg) levels by suppressing cell
      growth and increasing culture longevity through adaptation to higher osmolarity
      media and addition of sodium butyrate. Prior to adaptation, cells placed in
      higher osmotic pressures (350 and 400 mOsm) were severely suppressed in growth
      down to 25% of the control (300 mOsm), although total lg titers achieved were
      similar to the control, approximately 140 mg/L. After a week of adaptation to 350
      and 400 mOsm media, cell growth was not as dramatically suppressed, but
      considerably higher lg levels were attained at these elevated osmolarities. The
      highest yield of 265 mg/L was obtained at 350 mOsm compared to 140 mg/L at 300
      mOsm, while maximum viable cell numbers dropped from 35 x 10(5) cells/mL to 31 x
      10(5) cells/mL and culture longevity was extended by 20 h more than the control.
      Sodium butyrate, known to enhance protein production in other cell types, was
      then supplemented at a range of concentrations between 0.01 and 0.4 mM to the 350
      mOsm culture to further enhance the lg levels. Butyrate at a concentration of 0.1
      mM, in combination with osmotic pressure at 350 mOsm, further elevated the lg
      levels to 350 mg/L. Concomitantly, maximum viable cell numbers were reduced to 22
      x 10(5) cells/mL, but culture longevity was extended by 40 h in the 0.1 mM
      butyrate supplemented culture compared to the control condition. Specific
      antibody productivity, q(Mab), continued to stay high during the stationary phase
      and was further elevated during the decline phase: thus, overall lg levels can be
      increased by 2.3 times by combining osmotic pressure and butyrate treatment.

PMID- 18613083
TI  - Effect of surfactants on cellulose hydrolysis.
AB  - The effect of surfactants on the heterogeneous enzymatic hydrolysis of Sigmacell
      100 cellulose and of steam-exploded wood was studied. Certain biosurfactants
      (sophorolipid, rhamnolipid, bacitracin) and Tween 80 increased the rate of
      hydrolysis of Sigmacell 100, as measured by the amount of reducing sugar
      produced, by as much as seven times. The hydrolysis of steam-exploded wood was
      increased by 67% in the presence of sophorolipid. At the same time, sophorolipid
      was found to decrease the amount of enzyme adsorbed onto the cellulose at
      equilibrium. Sophorolipid had the greatest effect on cellulose hydrolysis when it
      was present from the beginning of the experiment and when the enzyme/cellulose
      ratio was low.

PMID- 18613084
TI  - Enantioselective synthesis of ibuprofen esters in AOT/isooctane microemulsions by
      Candida cylindracea lipase.
AB  - The enantioselective esterification of racemic ibuprofen, catalyzed by a Candida
      cylindracea lipase, was studied in a water-in-oil microemulsion (AOT/isooctane).
      By using n-propanol as the alcohol, an optimal W(0) ([H(2)O]/[AOT] ratio) of 12
      was found for the synthesis of n-propyl-ibuprofenate at room temperature. The
      lipase showed high preference for the S(+)-enantiomer of ibuprofen, which was
      esterified to the corresponding S(+)-ibuprofen ester. The R(-)-ibuprofen remained
      unesterified in the microemulsion. The calculated enantioselectivity value (E)
      for S-ibuprofen ester was greater than 150 (conversion 0.32). The enzyme
      activities of n-alcohols with different chain lengths (3-12) were compared, and
      it appeared that short- (propanol and butanol) and long-chained (decanol and
      dodecanol) alcohols were better substrates than the intermediate ones (pentanol,
      hexanol, and octanol). However, unlike secondary and tertiary alcohols, all of
      the tested primary alcohols were substrates for the lipase. The reversible
      reaction (i.e., the hydrolysis of racemic ibuprofen ester in the microemulsion)
      was also carried out enantioselectively by the enzyme. Only the S form of the
      ester was hydrolyzed to the corresponding S-ibuprofen. The reaction yield was,
      however, only about 4% after 10 days of reaction. The corresponding yield for the
      esterification of ibuprofen was about 35% (10 days). The high enantioselectivity
      displayed by the lipase in the microemulsion system was seen neither in a similar
      esterification reaction in a pure organic solvent system (isooctane) nor in the
      hydrolysis reaction in an aqueous system (buffer). The E value for S-ibuprofen
      ester in the isooctane system was 3.0 (conversion 0.41), and only 1.3 for S
      ibuprofen in the hydrolysis reaction (conversion 0.32). The differences in
      enantioselectivity for the lipase in various systems are likely due to
      interfacial phenomena. In the microemulsion system, the water in which the enzyme
      is dissolved is separated from the solvent by a layer of surfactant molecules,
      thus creating an interface with a relatively large area. Such interfaces are not
      present in the pure organic solvent systems (no surfactant) nor in aqueous
      systems.

PMID- 18613085
TI  - Fatty acid production characteristics of fungi with particular emphasis on gamma
      linolenic acid production.
AB  - The fatty acid production characteristics of fungi are described. These
      characteristics are the relationship between the oil content of the cell and the
      fatty acid content of the oil. For example, for polyunsaturated fatty acid (PUFA)
      production by Mucor hiemalis IPD 51, the oil content of the cell and the GLA
      content of the oil are coupled. For fungal production of some PUFA, synthesized
      after the rate-limiting step in the fatty acid anabolic chain, a maximum fatty
      acid production model was developed to link the fatty acid content of the oil and
      the oil content of the cell. Maximum volumetric productivity of gamma linolenic
      acid (GLA) by molds was found to occur at a specific GLA content of the oil. For
      example, for M. hiemalis IPD 51, a maximum volumetric of 4.7 mg GLA/L . h was
      produced at a GLA content of the oil of 8% to 10%. Similarly for Mucor
      circinelloides v. Tieghem IPD 155 a maximum volumetric productivity of 4.8 mg
      GLA/L . h was produced at a GLA content of the oil of 14% to 16%. These results
      imply that, when screening microorganisms for GLA or other fatty acid production,
      a number of medium compositions need to be evaluated to determine the tradeoff
      between oil content of the cell and fatty acid content of the oil.

PMID- 18613086
TI  - Cultivation of virus antigen in fibroblast cells using a glass fiber bed reactor.
AB  - The anchorage-dependent cell line, MRC-5, was cultivated successfully on glass
      fibers with diameters ranging from 24 to 120 mum, despite vast differences in
      substrate curvature. Multilayer cell growth was observed, particularly for fiber
      diameters 30 mum and below, which differed from the typical monolayer growth
      observed in T-flask cultivations. Cells were maintainable at a reduced incubation
      temperature and were demonstrated to support virus replication for the 21-day
      antigen production period. Direct microscopic observation, along with indirect
      calculations, indicated that only a small fraction (about 10%) of the total
      available fiber surface area was occupied by cells. Thus, productivity per unit
      surface area was replaced by productivity per unit medium volume when evaluating
      fiber bed performance. Antigen and protein yields, as well as nutrient uptakes,
      were 1.5- to 2.5-fold greater than parallel T-flask cultures when compared on
      this basis. Corresponding available surface area-based values were 10- to 15-fold
      lower for the fiber bed reactor. The multilayer cell morphology obtained in the
      fiber bed was attractive for antigen production when immobilized in a column
      reactor system.

PMID- 18613087
TI  - Competition between two microbial populations in a sequencing fed-batch reactor:
      theory, experimental verification, and implications for waste treatment
      applications.
AB  - Competition between two microbial populations for a single pollutant (phenol) was
      studied in a sequencing fed-batch reactor (SFBR). A mathematical model describing
      this system was developed and tested experimentally. It is based on specific
      growth rate expressions revealed from pure culture batch experiments. The species
      employed were Pseudomonas putida (ATCC 17514) and Pseudomonas resinovorans (ATCC
      14235). It was found that both species biodegrade phenol following inhibitory
      kinetics which can be described by Andrews' expression. The model predicts that
      the dynamics of a SFBR, and the kinetics of biodegradation, result in a complex
      set of operating regimes in which neither species, only one species, or both
      species can survive at steady cycle. The model also predicts the existence of
      multiple outcomes, achievable from different start-up conditions, in some domains
      of the operating parameter space. Experimental results confirmed the model
      predictions. There was excellent agreement between predicted and measured
      concentrations of phenol, total biomass, and the biomass of each individual
      species. This study shows how serious discrepancies can arise in scale-up of
      biodegradation data if population dynamics are not taken into account. It also
      further confirms experimentally the theory of microbial competition in
      periodically forced bioreactors.

PMID- 18613088
TI  - Optimization of alkyl beta-D-galactopyranoside synthesis from lactose using
      commercially available beta-galactosidases.
AB  - Commercially available lactase (beta-D-galactoside galactohydrolase, EC 3.2.1.23)
      enzymes produced from Kluyveromyces fragilis and Kluyveromyces lactis were
      accessed as catalysts for use in the production of beta-galactopyranosides of
      various alcohols using lactose as galactosyl donor. The yield of galactoside was
      enhanced by using the highest practical concentrations of both lactose and
      alcohol acceptor. The concentrations and thus yield, were limited by the
      solubility of the substrates. The increase in galactoside yield with increasing
      lactose concentration appeared to be specific to the lactose substrate and not
      due to water activity alterations, because addition of maltose to a fixed
      concentration of lactose had no effect. During the course of the reaction, the
      yield of galactoside peaked after around 70% to 80% of the lactose was consumed,
      due to hydrolysis of the product by the enzyme. A wide variety of compounds with
      primary or secondary hydroxyl groups could act as acceptors, the essential
      requirement being at least some water solubility. Addition of organic cosolvents
      had little effect on galactoside yield except when it increased the water
      solubility of sparingly soluble alcohols. Some galactosides were synthesized on a
      gram scale to determine practical product recoveries and improve purification
      methods for large-scale synthesis. Initial purification by hydrophobic
      chromatography (for galactosides of hydrophobic alcohols) or strong anion
      exchange chromatography (for galactosides of hydrophilic alcohols) separated
      galactosides, galactobiosides, and higher oligomers from reducing sugars. A
      facile separation of the galactoside and galactobioside could then be effected by
      flash chromatography on silica gel.

PMID- 18613089
TI  - Gas phase acetaldehyde production in a continuous bioreactor.
AB  - The gas phase continuous production of acetaldehyde was studied with particular
      emphasis on the development of biocatalyst (alcohol oxidase on solid phase
      support materials) for a fixed bed reactor. Based on the experimental results in
      a batch bioreactor, the biocatalysts were prepared by immobilization of alcohol
      oxidase on Amberlite IRA-400, packed into a column, and the continuous
      acetaldehyde production in the gas phase by alcohol oxidase was performed. The
      effects of the reaction temperature, flow rates of gaseous stream, and ethanol
      vapor concentration on the performance of the continuous bioreactor were
      investigated.

PMID- 18613091
TI  - Cheek pouch use, predation risk, and feeding competition in blue monkeys
      (Cercopithecus mitis stuhlmanni).
AB  - The adaptive function of cheek pouches in the primate subfamily Cercopithecinae
      remains unresolved. By analyzing the circumstances of cheek pouch use, we tested
      two hypotheses for the evolution of cercopithecine cheek pouches proposed in
      earlier studies: (1) cheek pouches reduce vulnerability to predation, and (2)
      cheek pouches increase feeding efficiency by reducing competition. We studied two
      groups of wild blue monkeys (Cercopithecus mitis stuhlmanni) in the Kakamega
      Forest, Kenya, conducting focal observations of feeding individuals. Monkeys were
      less exposed while emptying their cheek pouches than filling them, supporting the
      predation-avoidance hypothesis. We investigated several measures of competitive
      threat, but only one supported the competition-reduction hypothesis: when the
      nearest neighbor's rank increased, subjects were more likely to increase than to
      decrease cheek pouch use. Overall, our findings supported the predation-avoidance
      hypothesis more strongly than the competition-reduction hypothesis. We suggest
      that variation in cheek pouch use may reflect differing behavioral strategies
      used by cercopithecines to mitigate competition and predation, as well as factors
      such as resource size and distribution, home range size, and travel patterns.

PMID- 18613092
TI  - Synthesis of functional poly(phenyl isocyanide)s with macromolecular helicity
      memory and their use as asymmetric organocatalysts.
AB  - To develop a novel polymer-based asymmetric organocatalyst, a series of helical
      poly(phenyl isocyanide)s with functional pendant groups were prepared by
      modifying the side groups of the optically active helical poly(4-carboxyphenyl
      isocyanide) with a macromolecular helicity memory. Helical polyisocyanides
      partially modified with achiral amines, such as piperazine, maintained their
      chiral memory and enantioselectively catalyzed a direct aldol reaction. Although
      the enantioselectivity was low, the original helical poly(4-carboxyphenyl
      isocyanide) showed no catalytic activity. These results indicated that the
      macromolecular helicity of the modified polyisocyanides together with
      bifunctional amino and carboxy acid pendant residues arranged in a helical array
      along the polymer backbones plays an important role in the enantioselectivity.

PMID- 18613093
TI  - Greater sciatic notch as a sex indicator in juveniles.
AB  - Using Schutkowski's method for juvenile sex determination (Schutkowski H. 1993.
      Am J Phys Anthropol 90:199-205), we evaluated the morphology of the greater
      sciatic notch of 56 ilia (23 females and 33 males) from a documented skeletal
      collection housed at the Bocage Museum in Lisbon (Portugal). After applying
      Schutkowski's original methodology and comparing the results with previous
      studies, we used age-adjusted metrical variables to describe greater sciatic
      notch depth, breadth, and angle. Although results of both morphological and
      metrical analyses did not reveal a statistically significant level of sexual
      analyses dimorphism, we found a strong correlation between pelvic morphology and
      age at death. On the basis of the obtained results, we argue that Schutkowski's
      morphological method does not predict sex accurately in all populations and that
      recorded correlation of iliac features with age needs to be further explored in
      the context of the ontogeny of sexual dimorphism.

PMID- 18613094
TI  - Cognitive-behavioral conjoint therapy for posttraumatic stress disorder:
      application to operation enduring and Iraqi Freedom veterans.
AB  - As the newest generation of veterans returns home from their duties abroad, many
      face the individual and interpersonal aftereffects of duty-related traumatic
      experiences. Despite the established association between posttraumatic stress
      disorder (PTSD) and relationship problems, there is a lack of evidence-based
      conjoint treatments that target both PTSD and relationship distress. Cognitive
      behavioral conjoint therapy (CBCT) for PTSD was developed to address this need.
      The authors summarize knowledge on the association between PTSD and relationship
      functioning, as well as recent research on veterans and their partners. Following
      an overview of CBCT for PTSD, the authors present a case study to illustrate the
      application of CBCT to an Operation Enduring and Iraqi Freedom couple.

PMID- 18613095
TI  - Fretting crevice corrosion of stainless steel stem-CoCr femoral head connections:
      comparisons of materials, initial moisture, and offset length.
AB  - Modular tapers continue to be used in a wide variety of orthopedic implants. In
      this study, stainless steel (ASTM F-1568) femoral hip stems combined with Co-Cr
      Mo alloy heads (SS/CoCr) were tested in an in vitro fretting corrosion test set
      up to assess the propensity for mechanically assisted corrosion. Three different
      aspects of the modular design were evaluated in this study: (1) material
      combination compared to CoCr/CoCr, (2) wet versus dry assembly for SS/CoCr
      couples, and (3) 0- and 6-mm head offset for SS/CoCr couples. Fretting corrosion
      tests over a range of cyclic loads up to 3300 N were performed, and continuous
      cyclic loading at 3300 N for 1 M cycles were performed on each group (n = 5).
      Fretting micromotion was measured as a function of cyclic load on select couples
      to detect the nature and extent of motion present. The results showed that
      SS/CoCr couples were more susceptible to fretting corrosion than CoCr/CoCr
      couples, that dry assembly does not prevent fretting corrosion from taking place
      but raises the onset load, and that 6-mm offset heads had higher visual evidence
      of fretting damage but showed mixed statistical results in terms of onset loads
      and OCP shifts and currents compared to the 0-mm offset samples. Current and
      voltage excursions over 1 million cycles tended to diminish towards their
      unloaded control levels but did not fully recover until cyclic loading ceased.
      Micromotion measurements indicated fretting motions in the range of 10-25 microm
      where 0-mm heads tended to piston on the trunion, while 6 mm heads tended to
      rock.

PMID- 18613096
TI  - Retrieval of absorptive potential variation in electron beam sensitive specimens
      using a single energy-filtered bright-field TEM image.
AB  - A method is presented for retrieving the variation of the absorptive potential in
      electron beam sensitive soft material. The absorptive potential is directly
      related to the variations in atomic density and in chemical composition
      fluctuation. In our approach only a single zero-loss energy-filtered bright-field
      transmission electron microscopy (TEM) image is sufficient to obtain this
      information. The accuracy and the effectiveness of this proposed method has been
      tested using both simulation and experiment. As an experimental example of soft
      (organic) material, the variation in absorptive potential in an unstained tissue
      sample of zebrafish gill has been determined.

PMID- 18613100
TI  - Response dynamics of 26-, 34-, 39-, 54-, and 80-kDa proteases in induced cultures
      of recombinant Escherichia coli.
AB  - Several researchers have demonstrated that the presence of a heterologous protein
      in recombinant Escherichia coli elicits a response similar to the heat-shock
      response, which includes enhanced protease expression. The present work detects,
      quantifies, and characterizes intracellular protease activity in E. coli that are
      "shocked" by the induction of a recombinant protein, CAT, which is an endogenous
      protein in some E. coli strains. A novel, sodium dodecyl sulfate gelatin poly
      acrylamide gel electrophoresis (SDS-GPAGE) method is used to detect, quantify,
      and characterize the presence of these proteases. A hypothesis is proposed which
      links the amplified protease activity to a temporary depletion of specific amino
      acid pools, and a stringent-like stress response.

PMID- 18613097
TI  - CANDID: a flexible method for prioritizing candidate genes for complex human
      traits.
AB  - Genomewide studies and localized candidate gene approaches have become everyday
      study designs for identifying polymorphisms in genes that influence complex human
      traits. Yet, in general, the number of significant findings and the need to focus
      on smaller regions require a prioritization of genes for further study. Some
      candidate gene identification algorithms have been proposed in recent years to
      attempt to streamline this prioritization, but many suffer from limitations
      imposed by the source data or are difficult to use and understand. CANDID is a
      prioritization algorithm designed to produce impartial, accurate rankings of
      candidate genes that influence complex human traits. CANDID can use information
      from publications, protein domain descriptions, cross-species conservation
      measures, gene expression profiles and protein-protein interactions in its
      analysis. Additionally, users may supplement these data sources with results from
      linkage, association and other studies. CANDID was tested on well-known complex
      trait genes using data from the Online Mendelian Inheritance in Man database.
      Additionally, CANDID was evaluated in a modeled gene discovery environment, where
      it ranked genes whose trait associations were published after CANDID's databases
      were compiled. In all settings, CANDID exhibited high sensitivity and
      specificity, indicating an improvement upon previously published algorithms. Its
      accuracy and ease of use make CANDID a highly useful tool in study design and
      analysis for complex human traits.

PMID- 18613098
TI  - Children with new tracheostomies: planning for family education and common
      impediments to discharge.
AB  - OBJECTIVES: To describe an educational program and timeline for the discharge of
      children with a new tracheostomy and identify common impediments to the education
      and discharge process. METHODS: Retrospective pilot case series of 70 children
      and adolescents undergoing tracheostomy placement over a 24-month period in a
      large urban academic pediatric hospital. RESULTS: Eleven healthcare providers
      with expertise with technology dependent children identified the eight most
      common impediments to education and discharge for children with new
      tracheostomies. Length of stay, impediments to both education and discharge, and
      medical equipment needed at the time of discharge were extracted from hospital
      records. Caregivers of children with new tracheostomies needed a median of 14
      days (range 5-110 days) to successfully complete a tracheostomy education
      program. Discharge occurred a median of 6.5 days (range 0-71 days) after
      education was completed. Common impediments to completing the education program
      included social issues (e.g., lack of sibling childcare), inter-current illness
      of the patient and/or language barriers. Impediments to discharge included
      patient's inter-current illnesses, social issues (e.g., lack of running water)
      and unavailability of home nursing. Our cohort of patients had a total median
      length of stay (LOS) of 46 days. At discharge, 55% of children required two or
      more medical devices (in addition to their tracheostomy) and 61% had some level
      of dependency on positive pressure ventilation. CONCLUSIONS: Pediatric patients
      with a new tracheostomy undergo lengthy initial hospitalizations and have complex
      educational and discharge needs. Multiple factors (both medical and social) can
      impede the child's transition to the outpatient setting. A structured education
      and discharge program may result in a shorter LOS for children with new
      tracheostomies. Impediments to family education and discharge should be
      anticipated.

PMID- 18613101
TI  - Analysis of metabolic fluxes in batch and continuous cultures of Bacillus
      subtilis.
AB  - It is well recognized that metabolic fluxes are the key variables that must be
      determined in order to understand metabolic regulation and patterns. However,
      owing to difficulties in measuring the flux values, evaluation of metabolic
      fluxes has not been an integral part of the most metabolic studies. Flux values
      for metabolites of glycolysis, tricarboxylic acid (TCA) cycle, and hexose
      monophosphate (HMP) pathway were obtained for batch and glucose-limited
      continuous cultures of Bacillus subtilis by combining the information from the
      stoichiometry of key biosynthetic reactions with the experimental data on
      concentrations of glucose and metabolic by-products, CO(2) evolution, and oxygen
      uptake rates. The results indicate that (1) the metabolic fluxes and energetic
      yield as well as the extent of flux mismatch in metabolic activity of glycolysis
      and the TCA cycle reactions can be accurately quantified; (2) the flux through
      the TCA cycle in continuous culture is much in excess of cell energetic and
      biosynthetic demands for precursors; (3) for the range of growth rates examined
      the TCA cycle flux increases almost in proportion to growth rate and is
      significantly repressed only at very high growth rates of batch cultures; and (4)
      for continuous cultures the isocitrate dehydrogenase catalyzed reaction of the
      TCA cycle is the major source of the reduced form of nicotinamide-adenine
      dinucleotide phosphate (NADPH) used in biosynthesis.

PMID- 18613102
TI  - Utilization of glucose and amino acids in insect cell cultures: Quantifying the
      metabolic flows within the primary pathways and medium development.
AB  - The current understanding of insect cell metabolism is very limited. In order to
      gain some insight into the growth and metabolism of insect cells Spodoptera
      frugiperda (Sf9), a comprehensive characterization of culture conditions for
      cells grown in the IPL-41 medium was made by measuring the amino acid composition
      of the growth medium and the cell extract, the macromolecular composition of the
      cells (DNA, RNA, and protein), medium concentrations of various metabolites and
      sugars, and the evolved CO(2). Since in the IPL-41-based serum-free medium all of
      the amino acids except cysteine are in great excess of what is needed by the
      cells for energy and protein production, a medium formulation with an osmolarity
      similar to the IPL-41 but with a lower amino acid content than IPL-41 was also
      developed. The new medium also lacks maltose and sucrose (contains only glucose),
      supported cell growth to a high cell density of 8 x 10(6) cells/mL. The cellular
      and energetic yields indicated that a tight coupling between the biosynthetic and
      energetic reactions was attained for cells grown in the new medium. Moreover, it
      was found that the intermittent feeding of glucose may not be required as the
      cell yield and growth rate were comparable whether the same total amount of
      glucose was provided intermittently or was included initially in the medium. The
      eventual cessation of growth in the new medium is believed to be due to the amino
      acid limitation because concentrations of both glutamine and glutamate were very
      low at the end of the growth phase. Thus, further optimization, which may include
      higher initial glutamine in the medium or its intermittent feeding, could lead to
      a further increase in the cell density. Finally, a stoichiometrically based
      analysis of metabolic reactions confirmed the operation of the key pathways and
      was used to quantify the distribution of metabolites among primary metabolic
      reactions. The quantitative flow values were used to highlight some key aspects
      of insect cell metabolism.

PMID- 18613103
TI  - A single-cell assay of beta-galactosidase in recombinant Escherichia coli using
      flow cytometry.
AB  - A flow cytometric method was developed for the assay of beta-galactosidase in
      single Escherichia coli cells. A new fluorogenic substrate for beta
      galactosidase, C(12)FDG, contains a lipophilic group that allows the substrate to
      penetrate through cell membranes under normal conditions. When the substrate is
      hydrolyzed by intracellular beta-galactosidase, a green fluorescent product is
      formed and retained inside the cell. Consequently, the stained beta-galactosidase
      positive cells exhibit fluorescence, which is detected by flow cytometry. This
      new assay was used to analyze the segregational instability caused by a reduction
      in specific growth rate of the plasmid-bearing cells in the T7 expression system.
      Induction results in a substantial accumulation of intracellular beta
      galactosidase along with a rapid increase in the fraction of plasmid-free cells.
      Once the cells lose the plasmid, they no longer produce beta-galactosidase, which
      is reduced by at least half every generation; thus, after staining, the
      fluorescent, plasmid-bearing cells can be distinguished from the nonfluorescent,
      plasmid-free cells using flow cytometry. This article describes the feasibility
      of the flow cytometric assay for single E. coli cells and reports the optimal
      assay conditions. A direct relationship between beta-galactosidase activity and
      green fluorescence intensity was found, and the fractions of recombinant cells in
      batch cultures were analyzed after various levels of induction.

PMID- 18613104
TI  - Prevascularization of porous biodegradable polymers.
AB  - Highly porous biocompatible and biodegradable polymers in the form of cylindrical
      disks of 13.5 mm diameter were implanted in the mesentery of male syngeneic
      Fischer rats for a period of 35 days to study the dynamics of tissue ingrowth and
      the extent of tissue vascularity, and to explore their potential use as
      substrates for cell transplantation. The advancing fibrovascular tissue was
      characterized from histological sections of harvested devices by image analysis
      techniques. The rate of tissue ingrowth increased as the porosity and/or the pore
      size of the implanted devices increased. The time required for the tissue to fill
      the device depended on the polymer crystallinity and was smaller for amorphous
      polymers. The vascularity of the advancing tissue was consistent with time and
      independent of the biomaterial composition and morphology. Poly(L-lactic acid)
      (PLLA) devices of 5 mm thickness, 24.5% crystallinity, 83% porosity, and 166 mum
      median pore diameter were filled by tissue after 25 days. However, the void
      volume of prevascularized devices (4%) was minimal and not practical for cell
      transplantation. In contrast, for amporphous PLLA devices of the same dimensions,
      and the similar porosity of 87% and median pore diameter of 179 mum, the tissue
      did not fill completely prevascularized devices, and an appreciable percentage
      (21%) of device volume was still available for cell engraftment after 25 days of
      implantation. These studies demonstrate the feasibility of creating vascularized
      templates of amorphous biodegradable polymers for the transplantation of isolated
      or encapsulated cell populations to regenerate metabolic organs and tissues.

PMID- 18613105
TI  - Oxygen transfer in a pulse bioreactor.
AB  - Oxygen transfer in a novel pulse bioreactor has been evaluated. The agitator
      consists of a series of alternately fixed and movable parallel plates mounted so
      that the movable plates vibrate at 30 Hz causing a pulsating fluid motion. Pure
      oxygen, at pressures up to 5 atm, diffuses through silicone rubber tubing that
      also vibrates at 30 or 60 Hz. The main feature of this bioreactor is high oxygen
      transfer with low shear to prevent damage to fragile animal cell membranes. We
      estimate that sufficient oxygen can be supplied to support over 10(8) cells/mL of
      human diploid foreskin cells growing on microcarriers.

PMID- 18613106
TI  - Carbon and energy balances in cell-recycle cultures of Schizosaccharomyces pombe.
AB  - A strain of the fission yeast Schizosaccharomyces pombe was aerobically grown in
      a cell-recycle fermentor under various operating conditions, i.e., different
      bleeding rates and various separate feed rates of glucose and basal medium.
      Carbon and energy balances were analyzed during steady-state culture regimes,
      allowing growth yields and maintenance coefficients to be determined under
      glucose-limited and glucose-excess environments. Special attention was given to
      the metabolic shift from purely oxidative to respirofermentative glucose
      catabolism resulting from a change in the growth-limiting factor. No maintenance
      requirements for the carbon source and for energy were observed during glucose
      limited culture regimes and oxidative catabolism. Under glucose excess and
      respirofermentative metabolism, the m(G) coefficient was shown to be growth
      linked, whereas the enhancement of the apparent m(e) coefficient observed for
      increased residual glucose concentrations could be assigned to a decline in the
      ATP yield.

PMID- 18613107
TI  - Optimal operating policy of the ultrafiltration membrane bioreactor for enzymatic
      hydrolysis of cellulose.
AB  - The dilution rate of an ultrafiltration membrane bioreactor in the enzymatic
      hydrolysis of cellulose was optimized using the kinetic model developed by Fan
      and Lee.(4) The sequence of optimal dilution rates was found to generally consist
      of an initial period of a minimal value (batch period), a subsequent period of
      maximum dilution rate, a period of a second batch, and a final period of a
      singular dilution rate. The effects of operating conditions, such as beta
      glucosidase activity, operating time, maximum dilution rate, substrate feeding
      rate, and enzyme-to-substrate ratio on both the conversion yield and the sequence
      of optimal dilution rates were investigated. To evaluate the validity of kinetic
      model employed in this work, enzymatic hydrolysis was carried out using alpha
      cellulose as a substrate in the ultrafiltration membrane bioreactor. The
      experimental data were well consistent with the simulation results.

PMID- 18613108
TI  - Toxicity of homologous series of organic solvents for the gram-positive bacteria
      Arthrobacter and Nocardia Sp. and the gram-negative bacteria Acinetobacter and
      Pseudomonas Sp.
AB  - The toxicity of homologous series of organic solvents has been investigated for
      the gram-positive bacteria, Arthrobacter sp. and Nocardia sp., and the gram
      negative bacteria, Acinetobacter sp. and Pseudomonas sp. The hydrophobicity of
      the solvent, expressed by its logP(octanol), proves to be a good measure for the
      toxicity of solvents in a two-phase system. The transition from toxic to nontoxic
      solvents occurs between logP(octanol) 3 and 5 and depends on the homologous
      series. No correlation has been found between the hydrophobicity of the
      substituent on the alkyl backbone of the solvent and the location of the
      transition point in toxicity. The logP(octanol), above which all solvents are
      nontoxic, is used to express the solvent tolerance of the bacteria. In general,
      the solvent tolerance of gram-negative bacteria is found to be slightly higher
      than that of gram-positive bacteria, but this does not hold for all homologous
      series of organic solvents investigated.Because the toxicity effects of organic
      solvents in a two-phase system can be ascribed to molecular as well as phase
      toxicity effects, molecular toxicity effects were investigated separately in a
      one-phase system with subsaturating amounts of organic solvent. The solvent
      concentration in the aqueous phase, at which 50% of the metabolic activity of the
      bacteria is lost, is used to express solvent toxicity. This concentration is
      found to be similar for the gram-positive Arthrobacter and the gram-negative
      Acinetobacter. Assuming the critical membrane concentration theory (G. J. Osborne
      et al. Enzyme Microb. Technol. 1990, 12: 281-291) to be valid, it can be
      concluded that differences in solvent tolerance between these two bacteria,
      cannot be ascribed to differences in response to molecular toxicity. Prediction
      of the toxicity of any solvent, using the critical membrane theory, appears to be
      possible in the case of alkanols or alkyl acetates. However, prediction of the
      toxicity of ethers appears to be impossible.

PMID- 18613109
TI  - Modeling lipolysis in a reversed micellar system: part I. conventional batch
      reactor.
AB  - Triglyceride hydrolysis using Chromobacterium viscosum lipase B in a reversed
      micellar media was investigated in a batch-type reactor. The dynamic evolution of
      the product concentration was analyzed using several mechanistic models, both
      from the literature and developed in this work. A kinetic model with nonlinear
      product inhibition was found to be the most adequate for the description of batch
      hydrolysis data over an extensive range of time and substrate concentration. The
      obtained rate equation described the time course of not only the reactions
      performed in this work, at different water contents (W(0) = 7, 24) and pH values,
      but also the experimental results obtained in the literature with a Candida
      rugosa lipase.

PMID- 18613110
TI  - Modeling lipolysis in a reversed micellar system: part II-membrane reactor.
AB  - Olive oil hydrolysis using Chromobacterium viscosum lipase B in a reversed
      micellar media was investigated in a membrane reactor. The dynamic evolution of
      the product concentration both in the concentrate and permeate stream was
      analyzed using a mechanistic model previously developed by us and further
      modified in this work. A kinetic law with a second-order dependence in the
      substrate concentration and nonlinear product inhibition was found to be the most
      adequate for the description of the hydrolysis data over an extensive range of
      time and substrate concentration. These findings are discussed in terms of the
      specific interactions occurring in the membrane reactor.

PMID- 18613111
TI  - Pressure affects enzyme function in organic media.
AB  - Pressure affects enzyme function in nonaqueous media. Activation volumes have
      been determined and provide evidence that the primary effect of pressure is to
      enhance the stripping of water off an enzyme in polar organic solvents and leads
      to decreased enzymatic activity. Activation volumes of subtilisin Carlsberg in
      organic solvents, particularly with the enzyme hydrated, have a larger magnitude
      than activation volumes determined in aqueous solutions. This study provides
      further evidence that enzymatic activity in polar organic solvents is dominated
      by the interaction of enzyme-bound water with the solvent. From a practical
      standpoint, however, the results of this study suggest that enzymatic catalysis
      in organic solvents may be controlled by the combined effects of pressure and
      enzyme hydration.

PMID- 18613112
TI  - Morphological measurements on Penicillium chrysogenum broths by rheology and
      filtration methods.
AB  - The morphology parameters of mycelial culture (Penicillium chrysogenum) were
      measured and quantified by rheology and filtration methods. Two of the morphology
      parameters obtained from rheology measurements, delta defined by the Casson
      equation and delta* defined by intrinsic viscosity, were found to vary
      systematically with broth age and with the observed morphology by microscopy.
      Three of the filtration parameters, hyphal density, Kozeny constant, and index of
      compressibility, are demonstrated as sensitive indicators of the broth age and
      mycelial morphology. Two of the morphology parameters, delta and delta*, were
      used to cross-correlate with hyphal density. Because various mycelial
      fermentations require different growth morphologies (pellet and filament) for
      optimum product yield and the morphology of mycelial broths varies with broth
      age, it is suggested that these morphology parameters could be used to represent
      the morphology of mycelial broths quantitatively.

PMID- 18613113
TI  - Removal of lead from aqueous solutions by Penicillium biomass.
AB  - The removal of lead ions from aqueous solutions by adsorption on nonliving
      Penicillium chrysogenum biomass was studied. Biosorption of the Pb(+2) ion was
      strongly affected by pH. Within a pH range of 4 to 5, the saturated sorption
      uptake of Pb(+2) was 116 mg/g dry biomass, higher than that of activated charcoal
      and some other microorganisms. At pH 4.5, P. chrysogenum biomass exhibited
      selectivity for Pb(+2) over other metal ions such as Cd(+2), Cu(+2), Zn(+2), and
      As(+3) Sorption preference for metals decreased in the following order: Pb > Cd >
      Cu > Zn > As. The sorption uptake of Pb(+2) remained unchanged in the presence of
      Cu(+2) and As(+3), it decreased in the presence of Zn(+2), and increased in the
      presence of Cd(+2).

PMID- 18613114
TI  - Lipase-catalyzed acyiation of sugars solubilized in hydrophobic solvents by
      complexation.
AB  - By complexing glucose and other mono- and disaccharides with phenylboronic acid,
      they were solubilized in many organic solvents. Pseudomonas sp. lipoprotein
      lipase readily acylated such solubilized sugars in these solvents (no reaction
      was observed without phenylboronic acid, i.e., when sugars are insoluble in the
      reaction medium). Solubilized D-glucose was enzymatically acylated with vinyl
      acrylate on a preparative scale, and the resultant 6-O-acryloylglucose was
      chemically polymerized to yield a sugar-based polyacrylate with a molecular
      weight of 14,000 Da.

PMID- 18613115
TI  - Antigen-specific B cell detection reagents: use and quality control.
AB  - Tests for immunoglobulin reactivity with specific antigens are some of the oldest
      and most used assays in immunology. With efforts to understand B cell
      development, B cell dysregulation in autoimmunity, and to generate B cell
      vaccines for infectious agents, investigators have found the need to understand
      the ontogeny and regulation of epitope-specific B cell responses. The synchrony
      between surface and secreted antibodies for individual B cells has led to the
      development of reagents and techniques to identify antigen-specific B cells via
      reagent interactions with the B cell receptor complex. B cell antigen-specific
      reagents have been reported for model systems of haptens, for whole proteins, and
      for identification of double stranded (ds) DNA antibody-producing B cells using
      peptide mimics. Here we provide an overview of reported techniques for the
      detection of antigen-specific B cell responses via secreted antibody or by the
      surface B cell receptor and briefly discuss our recent work developing a panel of
      reagents to probe the B cell response to HIV-1 envelope. We also present an
      analysis of strengths and weaknesses of various methods for flow cytometric
      analysis of antigen-specific B cells.

PMID- 18613117
TI  - Beta-tubulin isotype classes II and V expression patterns in nonsmall cell lung
      carcinomas.
AB  - Previous studies suggest that beta-tubulin isotype protein levels could be useful
      as indicators of nonsmall cell lung cancer (NSCLC) aggressiveness. However,
      measurement of protein amounts in tissue samples by staining techniques is
      semiquantitative at best. Since technologies for measuring mRNA levels have
      become more efficient and quantitative, we wanted to determine whether beta
      tubulin message levels may be useful as biomarkers. Quantitative real-time RT-PCR
      was used to measure the seven classes of beta-tubulin isotypes, stathmin and MAP4
      mRNA levels in 64 NSCLC and 12 normal lung tissue samples. We found significantly
      higher fractions of beta-tubulin classes II and V mRNA compared to the other
      isotypes in all lung tumor samples (P < 0.05). In addition, the ratio of beta
      tubulin classes II/V mRNA was significantly higher in NSCLCs compared to normal
      lung tissues (P < 0.001). The data suggest that the ratio of beta-tubulin classes
      II and V mRNA could be useful as a biomarker for NSCLC tumor differentiation
      and/or NSCLC aggressiveness. Furthermore, the ratio of MAP4 to stathmin mRNA was
      found to be higher in diseased lung tissues compared to normal lung tissues,
      suggesting this ratio might also be used as a clinically relevant biomarker for
      NSCLCs.

PMID- 18613116
TI  - CaMK-II promotes focal adhesion turnover and cell motility by inducing tyrosine
      dephosphorylation of FAK and paxillin.
AB  - Transient elevations in Ca2+ have previously been shown to promote focal adhesion
      disassembly and cell motility through an unknown mechanism. In this study,
      evidence is provided to show that CaMK-II, a Ca2+/calmodulin dependent protein
      kinase, influences fibroblast adhesion and motility. TIRF microscopy reveals a
      dynamic population of CaMK-II at the cell surface in migrating cells. Inhibition
      of CaMK-II with two mechanistically distinct, membrane permeant inhibitors (KN-93
      and myr-AIP) freezes lamellipodial dynamics, accelerates spreading on
      fibronectin, enlarges paxillin-containing focal adhesions and blocks cell
      motility. In contrast, constitutively active CaMK-II is not found at the cell
      surface, reduces cell attachment, eliminates paxillin from focal adhesions and
      decreases the phospho-tyrosine levels of both FAK and paxillin; all of these
      events can be reversed with myr-AIP. Thus, both CaMK-II inhibition and
      constitutive activation block cell motility through over-stabilization or
      destabilization of focal adhesions, respectively. Coupled with the existence of
      transient Ca2+ elevations and a dynamic CaMK-II population, these findings
      provide the first direct evidence that CaMK-II enables cell motility by
      transiently and locally stimulating tyrosine dephosphorylation of focal adhesion
      proteins to promote focal adhesion turnover.

PMID- 18613118
TI  - Multipoint lods provide reliable linkage evidence despite unknown limiting
      distribution: type I error probabilities decrease with sample size for multipoint
      lods and mods.
AB  - We investigate the behavior of type I error rates in model-based multipoint (MP)
      linkage analysis, as a function of sample size (N). We consider both MP lods
      (i.e., MP linkage analysis that uses the correct genetic model) and MP mods
      (maximizing MP lods over 18 dominant and recessive models). Following Xing and
      Elston (2006 Genet. Epidemiol, 30: 447-458), we first consider MP linkage
      analysis limited to a single position; then we enlarge the scope and maximize the
      lods and mods over a span of positions. In all situations we examined, type I
      error rates decrease with increasing sample size, apparently approaching zero. We
      show: (a) For MP lods analyzed only at a single position, well-known statistical
      theory predicts that type I error rates approach zero. (b) For MP lods and mods
      maximized over position, this result has a different explanation, related to the
      fact that one maximizes the scores over only a finite portion of the parameter
      range. The implications of these findings may be far-reaching: Although it is
      widely accepted that fixed nominal critical values for MP lods and mods are not
      known, this study shows that whatever the nominal error rates are, the actual
      error rates appear to decrease with increasing sample size. Moreover, the actual
      (observed) type I error rate may be quite small for any given study. We conclude
      that MP lod and mod scores provide reliable linkage evidence for complex
      diseases, despite the unknown limiting distributions of these MP scores.

PMID- 18613119
TI  - The knock-out of ARP3a gene affects F-actin cytoskeleton organization altering
      cellular tip growth, morphology and development in moss Physcomitrella patens.
AB  - The seven subunit Arp2/3 complex is a highly conserved nucleation factor of actin
      microfilaments. We have isolated the genomic sequence encoding a putative Arp3a
      protein of the moss Physcomitrella patens. The disruption of this ARP3A gene by
      allele replacement has generated loss-of-function mutants displaying a complex
      developmental phenotype. The loss-of function of ARP3A gene results in shortened,
      almost cubic chloronemal cells displaying affected tip growth and lacking
      differentiation to caulonemal cells. In moss arp3a mutants, buds differentiate
      directly from chloronemata to form stunted leafy shoots having differentiated
      leaves similar to wild type. Yet, rhizoids never differentiate from stem
      epidermal cells. To characterize the F-actin organization in the arp3a-mutated
      cells, we disrupted ARP3A gene in the previously described HGT1 strain expressing
      conditionally the GFP-talin marker. In vivo observation of the F-actin
      cytoskeleton during P. patens development demonstrated that loss-of-function of
      Arp3a is associated with the disappearance of specific F-actin cortical
      structures associated with the establishment of localized cellular growth
      domains. Finally, we show that constitutive expression of the P. patens Arp3a and
      its Arabidopsis thaliana orthologs efficiently complement the mutated phenotype
      indicating a high degree of evolutionary conservation of the Arp3 function in
      land plants.

PMID- 18613120
TI  - Wolfram syndrome 1 (Wfs1) gene expression in the normal mouse visual system.
AB  - Wolfram syndrome (OMIM 222300) is a neurodegenerative disorder defined by insulin
      dependent diabetes mellitus and progressive optic atrophy. This syndrome has been
      attributed to mutations in the WFS1 gene, which codes for a putative multi
      spanning membrane glycoprotein of the endoplasmic reticulum. The function of WFS1
      (wolframin), the distribution of this protein in the mammalian visual system, and
      the pathogenesis of optic atrophy in Wolfram syndrome are unclear. In this study
      we made a detailed analysis of the distribution of Wfs1 mRNA and protein in the
      normal mouse visual system by using in situ hybridization and
      immunohistochemistry. The mRNA and protein were observed in the retina, optic
      nerve, and brain. In the retina, Wfs1 expression was strong in amacrine and
      Muller cells, and moderate in photoreceptors and horizontal cells. In addition,
      it was detectable in bipolar and retinal ganglion cells. Interestingly, moderate
      Wfs1 expression was seen in the optic nerve, particularly in astrocytes, while
      little Wfs1 was expressed in the optic chiasm or optic tract. In the brain,
      moderate Wfs1 expression was observed in the zonal, superficial gray, and
      intermediate gray layers of the superior colliculus, in the dorsomedial part of
      the suprachiasmatic nucleus, and in layer II of the primary and secondary visual
      cortices. Thus, Wfs1 mRNA and protein were widely distributed in the normal mouse
      visual system. This evidence may provide clues as to the physiological role of
      Wfs1 protein in the biology of vision, and help to explain the selective
      vulnerability of the optic nerve to WFS1 loss-of-function.

PMID- 18613122
TI  - The impact of socioeconomic status on survival after cancer in the United States
      : findings from the National Program of Cancer Registries Patterns of Care Study.
AB  - BACKGROUND: Understanding the ways in which socioeconomic status (SES) affects
      mortality is important for defining strategies to eliminate the unequal burden of
      cancer by race and ethnicity in the United States. METHODS: Disease stage,
      treatment, and 5-year mortality rates were ascertained by reviewing medical
      records, and SES was determined by analyzing income and education at the census
      tract level for 4844 women with breast cancer, 4332 men with prostate cancer, and
      4422 men and women with colorectal cancer who were diagnosed in 7 U.S. states in
      1997. RESULTS: Low SES was associated with more advanced disease stage and with
      less aggressive treatment for all 3 cancers. The hazard ratio (HR) for 5-year all
      cause mortality associated with low SES was elevated after a diagnosis of breast
      cancer when the analysis was adjusted for age (HR, 1.59; 95% confidence interval
      [CI], 1.35-1.87). Adjustment for mediating factors of race/ethnicity, comorbid
      conditions, cancer stage, and treatment reduced the association. The age-adjusted
      mortality risk associated with low SES was elevated after a diagnosis of prostate
      cancer (HR, 1.33; 95% CI, 1.13-1.57), and multivariate adjustments for mediating
      factors also reduced that association. There was less association between SES and
      mortality after a diagnosis of colorectal cancer. For all 3 cancer sites, low SES
      was a much stronger predictor of mortality among individuals aged <65 years and
      among individuals from racial/ethnic minority groups. CONCLUSIONS: The current
      results indicated that low SES is a risk factor for all-cause mortality after a
      diagnosis of cancer, largely because of a later stage at diagnosis and less
      aggressive treatment. These findings support the need to focus on SES as an
      underlying factor in cancer disparities by race and ethnicity.

PMID- 18613121
TI  - Distinct molecular pathways for development of telencephalic interneuron subtypes
      revealed through analysis of Lhx6 mutants.
AB  - Here we analyze the role of the Lhx6 lim-homeobox transcription factor in
      regulating the development of subsets of neocortical, hippocampal, and striatal
      interneurons. An Lhx6 loss-of-function allele, which expresses placental alkaline
      phosphatase (PLAP), allowed analysis of the development and fate of Lhx6
      expressing interneurons in mice lacking this homeobox transcription factor. There
      are Lhx6+;Dlx+ and Lhx6-;Dlx+ subtypes of tangentially migrating interneurons.
      Most interneurons in Lhx6(PLAP/PLAP) mutants migrate to the cortex, although less
      efficiently, and exhibit defects in populating the marginal zone and superficial
      parts of the neocortical plate. By contrast, migration to superficial parts of
      the hippocampus is not seriously affected. Furthermore, whereas parvalbumin+ and
      somatostatin+ interneurons do not differentiate, NPY+ interneurons are present;
      we suggest that these NPY+ interneurons are derived from the Lhx6-;Dlx+ subtype.
      Striatal interneurons show deficits distinct from pallial interneurons, including
      a reduction in the NPY+ subtype. We provide evidence that Lhx6 mediates these
      effects through promoting expression of receptors that regulate interneuron
      migration (ErbB4, CXCR4, and CXCR7), and through promoting the expression of
      transcription factors either known (Arx) or implicated (bMaf, Cux2, and NPAS1) in
      controlling interneuron development.

PMID- 18613123
TI  - Ribosome display selection of a metal-binding motif from an artificial peptide
      library.
AB  - A new ribosome display system was applied for the in vitro selection of a metal
      binding motif from an artificial peptide library. The display system consisted of
      an mRNA-associating protein, a ribosome, and mRNA. The protein part of this
      display system was designed to provide a random peptide library and to stabilize
      the ribosome display. The random peptide library was newly designed to isolate
      stable metal-binding motifs. We employed the system for in vitro selection and
      found several new proteins and peptides that bind Co(II)-immobilized resin and
      Co(II)-complex, respectively. This newly developed system can be conveniently
      applied to the in vitro selection of peptide aptamers.

PMID- 18613125
TI  - Improvement of shikonin productivity in Lithospermum erythrorhizon cell culture
      by alternating carbon and nitrogen feeding strategy.
AB  - Stationary phase cell suspension cultures of Agrobacterium tumefaciens
      transformed Lithospermum erythrorhizon respond to additions of sucrose-rich (C
      rich) medium with a 2-3-fold increase in the accumulation of shikonin derivatives
      and a 3-3.5-fold increase in the accumulation of soluble phenolics while showing
      a modest (10-30%) increase in cell concentration. Conversely, the addition of
      nitrate-rich (N-rich) medium resulted in 25-35% increase in biomass concentration
      but only 2-9% increase in shikonin production and approximately 3% increase in
      the yield of soluble phenolics. Repeated additions of C-rich medium resulted in
      only a modest (less than 10%) improvement in shikonin production over the levels
      obtained after the first application. No obvious correlation could be discerned
      between intracellular ATP levels or protein synthesis patterns and the pattern of
      shikonin accumulation following the addition of C-rich medium, suggesting that
      the precursor diversion mechanism is not generally applicable in our cell line.
      It was found that alternating feeding of N-rich and C-rich media could be used as
      an effective strategy for enhancing the productivity of plant secondary
      metabolite.

PMID- 18613126
TI  - Enhancement effect of water activity on enzymatic synthesis of cephalexin.
AB  - The effect of water activity (a(w)) of the reaction medium on the enzymatic
      synthesis of cephalexin (CEX) from 7-amino-3-deacetoxycephalosporanic acid (7
      ADCA) and D-alpha-phenylglycine methyl ester (PGM) was investigated using the
      alpha-amino acid ester hydrolase enzyme from Xanthomonas citri. It was found that
      the synthetic activity of the enzyme and the conversion yield were markedly
      improved when the a(w) of the reaction medium was lowered to about 0.97. The
      water activity depressing agents evaluated were glycerol, sucrose, and sorbitol,
      and the conversion yields were improved up to 170% with 15% glycerol, 230% with
      30% sucrose, and 270% with 20% sorbitol, respectively. The extent of favorable
      effect of a(w) on the conversion yield was not the same among the a(w)
      depressors, probably due to other unknown interactions between the enzyme and
      depressors. However, optimal a(w) values corresponding to the maximum conversion
      yield coincided for all a(w) depressors used. The conversion yield of CEX showed
      an increasing trend with increasing a(w) up to the optimal a(w) value (0.96-0.97)
      which corresponds to the maximum conversion yield and a decreasing trend beyond
      the optimal a(w). There appears to be a delicate balance between the hydrolytic
      reaction of PGM and synthetic reaction of CEX. The increasing a(w)-[E . PGM]
      complex and the branched reaction pathway fluxes from [E . PGM] to PG (D-alpha
      phenyl glycine) and CEX are balanced in such a way that the maximum CEX
      conversion yield is obtained at a(w) value of 0.96-0.97. The a(w) depressors
      stabilized the enzyme somewhat, but this positive effect was considered to be
      only a minor contribution to the substantial yield enhancement. The a(w)
      depressor effect on viscosity and in turn the mass transfer rate limitation was
      ruled out since the change in conversion due to the viscosity change was found to
      be insignificant.

PMID- 18613127
TI  - Numerical and Monte Carlo simulations of phenolic polymerizations catalyzed by
      peroxidase.
AB  - Numerical and Monte Carlo simulations of horseradish peroxidase-catalyzed
      phenolic polymerizations have been performed. Kinetic constants for the
      simulations were fit to data from the oxidation and polymerization of bisphenol
      A. Simulations of peroxidase-catalyzed phenolic polymerization were run as a
      function of enzyme concentration and radical transfer and radical coupling rate
      constants. Predictions were performed with respect to conversion vs. time and
      number average molecular weight and polydispersity vs. conversion. It is shown
      that the enzymatic polymerization of phenols can be optimized with respect to
      high molecular weights by employing low enzyme concentrations and phenols with
      low radical coupling rate constants coupled with relatively high radical transfer
      rate constants. Such phenols may be identified by using linear free energy
      relationships that relate radical reactivity to electron donating/withdrawing
      potential of the phenolic substituent.

PMID- 18613128
TI  - Application of computer to monitoring and control of fermentation process:
      Microbial conversion of ML-236B Na to pravastatin.
AB  - An automatic feeding process for microbial hydroxylation of ML236B sodium salt
      (ML-236B Na; compactin) by Streptomyces carbophilus SANK 62585 was developed. The
      hydroxylated product, pravastatin sodium salt (pravastatin; trade name
      Mevalotin), is an inhibitor of 3-hydroxy-3-methyglutaryl-coenzyme A reductase
      (HMG-CoA reductase) used as cholesterol-lowering drug. The hydroxylation activity
      of S. carbophilus was induced by the addition of ML236B Na to culture broth but
      inhibited by high concentration of ML236B Na. In order to obtain high conversion
      yield, it was necessary to maintain optimum ML236B Na concentration throughout
      the fermentation by continuous feeding. For this purpose, we developed an on-line
      monitoring method, which mainly consisted of a cross-flow filtration module, high
      performance liquid chromatography (HPLC) analyzer, feed pump, and microcomputer
      for regulation of ML236B Na concentration. An algorithm for control of ML236B Na
      feed rate based on feedback and feed-forward control where conversion rate after
      Deltat was estimated by using regression analysis of the five latest values of
      conversion rate. In a fed-batch culture employing this system, the concentration
      of ML236B Na was maintained at optimum level during the fermentation and the
      productivity of pravastatin was increased threefold over that obtained in manual
      control culture.

PMID- 18613129
TI  - Lipase immobilized on hydrophobic porous polymer supports prepared by
      concentrated emulsion polymerization and their activity in the hydrolysis of
      triacylglycerides.
AB  - Microporous polymer supports for the immobilization of lipase have been prepared
      by the polymerization of a concentrated emulsion precursor. The concentrated
      emulsion consists of a mixture of styrene and divinyl-benzene containing a
      suitable surfactant and an initiator as the continuous phase and water as the
      dispersed phase. The volume fraction of the latter phase was greater than 0.74,
      which is the volume fraction of the dispersed phase for the most compact
      arrangement of spheres of equal radius. The lipase from Candida rugosa has been
      immobilized on the internal surface of the hydrophobic microporous poly(styrene
      divinyl benzene) supports and used as biocatalysts for the hydrolysis of
      triacylglycerides. The effects of the amount of surfactant, of the molar ratio of
      divinylbenzene/styrene in the continuous phase, and of the aquaphilicity of the
      supports on the adsorption, activity, and stability of the immobilized lipase
      have been investigated. The microporous poly(styrene-divinylbenzene) adsorbents
      constitute excellent supports for lipase because both the amount adsorbed is
      large and the rate of enzymatic reaction per molecule of lipase is higher for the
      immobilized enzyme than for the free one.

PMID- 18613130
TI  - Application of continuous zone electrophoresis to preparative separation of
      proteins.
AB  - A comprehensive study of the application of continuous zone electrophoresis to
      preparative separation of proteins in free solution is presented. First, the
      influence of electric field strength, buffer residence time in the chamber,
      sample flow rate, and sample concentration on separation resolution and
      throughput were studied. Using multiple injections of sample into the
      electrophoresis chamber, a throughput of 500 mg protein/h was achieved for
      partially purified model proteins. Experiments on Escherichia coli crude extracts
      yielded a fivefold purification of beta-galactosidase along with a simultaneous
      separation of proteins from cell debris in a single step. Experiments correlating
      the electrophoretic mobility in continuous electrophoresis with the elution
      behavior in ion-exchange chromatography were performed on more than a dozen
      proteins which conclusively showed that separation of proteins in continuous zone
      electrophoresis is governed by net surface charge. Based on these results, the
      fraction numbers in which the proteins eluted could be correctly predicted.
      Proteins and enzymes with differences >0.5 M elution molarities in ion-exchange
      chromatography were separated by continuous zone electrophoresis on a preparative
      scale (mg/h or g/h) with >90% recovery. This corresponds to a preparative scale
      separation of proteins and enzymes which differ in apparent electrophoretic
      mobility by only 0.70 x 10(-5) cm(2)/V . s.

PMID- 18613131
TI  - Stimulation of acid phosphatase induction in Saccharomyces cerevisiae by
      electrochemical modulation of effector concentration.
AB  - A novel modulating method of the expression of Saccharomyces PHO 5 gene,
      responsible for acid phosphatase (APase), is proposed. The method is based on
      electrochemical modulation of an effector (inorganic phosphate) concentration, as
      the gene expression is initiated below a threshold concentration of phosphate and
      is terminated above the threshold value. By positioning the yeast in the close
      neighborhood of a conducting polymer, the authors show the effectiveness of the
      electrochemical approach toward PHO 5 induction. Based on the approach, phosphate
      concentration is easily modulated at the boundary concentration by taking
      advantage of anion doping-undoping at a conducting polymer and the resulting
      anion localization-delocalization in the polymer, as the local enrichment of
      phosphate in the polymer results in the lowering of phosphate in the vicinity of
      polypyrrole. External phosphate concentration is thus electrochemically modulated
      when the conducting polymer is positioned in the close neighborhood of the yeast
      cells; thereby the PHO gene is induced. Here an electrochemical approach for the
      APase expression as a strategy of selective induction of specific genetic
      information is described. (c) 1993 John Wiley & Sons, Inc.

PMID- 18613132
TI  - An integrated metabolic modeling approach to describe the energy efficiency of
      Escherichia coli fermentations under oxygen-limited conditions: Cellular
      energetics, carbon flux, and acetate production.
AB  - An integrated metabolic model for the production of acetate by growing
      Escherichia coli on glucose under aerobic conditions is presented. The model is
      based on parameters which are easily determined by experiments. Forming the basis
      for this integrated metabolic model are the 12 principal precursor metabolites
      for biosynthetic pathways, the Embden-Meyerhof-Parnas pathway, the pentose
      phosphate cycle, the tricarboxylic acid cycle and the anapleurotic reactions, the
      Crabtree effect, the Pasteur effect, and the details of bacterial respiration.
      The result can be used to explain phenomena often observed in industrial
      fermentations, i.e., increased acetate production which follows from high glucose
      uptake rate, a low oxygen concentration, a high specific growth rate, or a
      combination of these conditions.

PMID- 18613133
TI  - Removal of phenols from wastewater by soluble and immobilized tyrosinase.
AB  - An enzymatic method for removal of phenols from industrial wastewater was
      investigated. Phenols in an aqueous solution were removed after treatment with
      mushroom tyrosinase. The reduction order of substituted phenols is catechol > p
      cresol > p-chlorophenol > phenol > p-methoxyphenol. In the treatment of
      tyrosinase alone, no precipitate was formed but a color change from colorless to
      dark-brown was observed. The colored products were removed by chitin and chitosan
      which are available abundantly as shellfish waste. In addition, the reduction
      rate of phenols was observed to be accelerated in the presence of chitosan.
      Tyrosinase, immobilized by using amino groups in the enzyme on cation exchange
      resins, can be used repeatedly. By treatment with immobilized tyrosinase, 100% of
      phenol was removed after 2 h, and the activity was reduced very little even after
      10 repeat treatments.

PMID- 18613134
TI  - TCE degradation in a methanotrophic attached-film bioreactor.
AB  - Trichloroethene was degraded in expanded-bed bioreactors operated with mixed
      culture methanotrophic attached films. Biomass concentrations of 8 to 75 g
      volatile solids (VS) per liter static bed (L(sb)) were observed. Batch TCE
      degradation rates at 35 degrees C followed the Michaelis-Menten model, and a
      maximum TCE degradation rate (q(max)) of 10.6 mg TCE/gVS . day and a half
      velocity coefficient (K(S)) of 2.8 mg TCE/L were predicted. Continuous-flow
      kinetics also followed the Michaelis-Menten model, but other parameters may be
      limiting, such as dissolved copper and dissolved methane-q(max) and K(S) were 2.9
      mg TCE/gVS . day and 1.5 mg TCE/L, respectively, at low copper concentrations
      (0.003 to 0.006 mg Cu/L). The maximum rates decreased substantially with small
      increases in dissolved copper. Methane consumption during continuous-flow
      operation varied from 23 to 1200 g CH(4)/g TCE degraded. Increasing the influent
      dissolved methane concentration from 0.01 mg/L to 5.4 mg/L reduced the TCE
      degradation rate by nearly an order of magnitude at 21 degrees C. Exposure of
      biofilms to 1.4 mg/L tetrachloroethene (PCE) at 35 degrees C resulted in the loss
      of methane utilization ability. Tests with methanotrophs grown on granular
      activated carbon indicated that lower effluent TCE concentrations could be
      obtained. The low efficiencies of TCE removal and low degradation rates obtained
      at 35 degrees C suggest that additional improvements will be necessary to make
      methanotrophic TCE treatment attractive.

PMID- 18613135
TI  - Bioenergetics and end-product regulation of Clostridium thermosaccharolyticum in
      response to nutrient limitation.
AB  - Fermentation of xylose by Clostridium thermosaccharolyticum was studied in batch
      and continuous culture in which the limiting nutrient was either xylose,
      phosphate, or ammonia. Transient results obtained in continuous cultures with
      batch grown inoculum and progressively higher feed substrate concentrations
      exhibited ethanol selectivities (moles ethanol/moles other products) in excess of
      11. The hypothesis that this high ethanol selectivity was a general response to
      mineral nutrient limitation was tested but could not be supported. Growth and
      substrate consumption were related by the equation q(s)(1 - Y(x) (c))G(ATP) =
      (mu/Y(ATP) (max)) + m, with q(s) the specific rate of xylose consumption (moles
      xylose/hour . g cells), Y(x) (c) the carbon based cell yield (g cell carbon/g
      substrate carbon), G(ATP) the ATP gain (moles ATP produces/mol substrate
      catabolized), micro the specific growth rate (1/h), Y(ATP) (max) the ATP-based
      cell yield (g cells/mol ATP), and m the maintenance coefficient (moles ATP/hour .
      g cells). Y(ATP) (max) was found to be 11.6 g cells/mol ATP, and m 9.3 mol
      ATP/hour . g cells for growth on defined medium. Different responses to nutrient
      limitation were observed depending on the mode of cultivation. Batch and
      immobilized cell continuous cultures decreased G(ATP) by initiating production of
      the secondary metabolites, propanediol, and in some cases, D-lactate; in
      addition, batch cultures increased the fractional allocation of ATP to
      maintenance and/or wastage. Nitrogen-limited continuous free-cell cultures
      maintained a constant cell yield, whereas phosphate-limited continuous free-cell
      cultures did not. In the case of phosphate limitation, the decreased ATP demand
      associated with the lowered cell yield was accompanied by an increased rate of
      ATP consumption for maintenance and/or wastage. Neither nitrogen or phosphorus
      limited continuous free-cell cultures exhibited an altered G(ATP) in response to
      mineral nutrient limitation, and neither produced secondary metabolites.

PMID- 18613136
TI  - Perfusion strategy for rosmarinic acid production by Anchusa officinalis.
AB  - The production of an intracellular secondary metabolite rosmarinic acid (RA) by
      plant cell suspensions of Anchusa officinalis cultivated with intermittent medium
      exchange is investigated. Initially, a two-stage perfusion culture method was
      employed. After being cultured in the batch mode for ca. 6 days in B5 medium plus
      3% sucrose, 1 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), and 0.1 mg/L kinetin
      (2,4-D B5 medium), Anchusa culture was cultivated to high cell density by
      perfusion during the growth stage using a hormone-free Gamborg B5 medium
      supplemented with 6% sucrose. This was followed by a production stage, in which a
      complete medium exchange into B5 medium plus 3% sucrose and 0.25 mg/L
      naphthleneacetic acid (NAA) was conducted. The two-stage perfusion culture had a
      higher maximum culture RA concentration but a lower RA content per cell than the
      batch stock culture maintained in the 2,4-D B5 medium. Higher culture RA
      concentration was due primarily to high cell density. The high packed cell
      volume, however, seemed to reduce the synergistic effect of NAA on RA synthesis.
      Subsequently, a single-stage perfusion culture method was investigated. The best
      result was obtained by growing the culture in the batch mode for ca. 10 days
      using B5 medium supplemented with 3% sucrose and 0.25 mg/L NAA, followed by
      perfusing the culture with B5 medium plus 6% sucrose and 0.25 mg/L NAA at a
      constant perfusion rate of 0.1/day. A maximum cell dry weight of 35 g/L and a RA
      concentration of almost 4 g/L were achieved. This is the highest RA concentration
      ever reported in the Anchusa culture.

PMID- 18613137
TI  - A two-plane tubular photobioreactor for outdoor culture of Spirulina.
AB  - A photobioreactor in the form of a 245-m-long loop made of plexiglass tubes
      having an inner diameter of 2.6 cm was designed and constructed for outdoor
      culture of Spirulina. The loop was arranged in two planes, with 15 8-m-long tubes
      in each plane. In the upper plane, the tubes were placed in the vacant space
      between the ones of the lower plane. The culture recycle was performed either
      with two airlifts, one per plane, or with two peristaltic pumps. The power
      required for water recycle in the tubular photobioreactor, with a Reynolds number
      of 4000, was 3.93 x 10(-2) W m(-2). The photobioreactor contained 145 L of
      culture and covered an overall area of 7.8 m(2). The photobioreactor operation
      was computer controlled. Viscosity measurements performed on Spirulina cultures
      having different biomass concentrations showed non-Newtonian behavior displaying
      decreasing viscosity with an increasing shear rate. The performance of the two
      plane photobioreactor was tested under the climatic conditions of central Italy
      (latitude 43.8 degrees N, longitude 11.3 degrees E). A biomass concentration of
      3.5 g L(-1) was found to be adequate for outdoor culture of Spirulina. With a
      biomass concentration of 6.3 g L(-1), the biomass output rate significantly
      decreased. The net biomass output rate reached a mean value of 27.8 g m(-2) d(-1)
      in July; this corresponded to a net photosynthetic efficiency of 6.6% (based on
      visible irradiance).

PMID- 18613138
TI  - Adsorption of Clostridium thermocellum cellulases onto pretreated mixed hardwood,
      avicel, and lignin.
AB  - Adsorption of Avicel-hydrolyzing activity was examined with respect to: mixed
      hardwood flour pretreated with 1% sulfuric acid for 9 s at 220 degrees C
      (PTW220), lignin prepared from PTW220 by either acid or enzymatic hydrolysis, and
      Avicel. Experiments were conducted at 60 degrees C for all materials, and also at
      25 degrees C for PTW220. Based on transient adsorption results and reaction
      rates, times were selected at which to characterize adsorption at 60 degrees C as
      follows: PTW220, 1 min; lignin, 30 min; and Avicel, 45 min. Similar results were
      obtained for adsorption of cellulase activity to PTW220 at 25 and 60 degrees C,
      and for lignin prepared by enzymatic and acid hydrolysis. For all materials,
      adsorption was described well by a Langmuir equation, although the reversibility
      of adsorption was not investigated. Langmuir affinity constants (L/g) were:
      PTW220, 109; lignin, 17.9; Avicel, 4.3; cellulose from PTW220, > or =187.
      Langmuir capacity constants were 760 for PTW220 and 42 for Avicel; the cellulase
      binding capacity of lignin appeared to be very high under the conditions
      examined, and could not be determined. At low and moderate cellulase loadings at
      least, the majority of cellulase activity adsorbed to PTW220 is bound to the
      cellulosic component. The results indicate that PTW220, and its cellulose
      component in particular, differ radically from Avicel with respect to adsorption.
      Avicel-hydrolyzing activity and CMC-hydrolyzing activities were found to bind to
      Avicel with a constant ratio of essentially one, consistent with adsorption of a
      multi-activity complex.

PMID- 18613140
TI  - Review: tissue engineering: reconstitution of human hematopoiesis ex vivo.
AB  - The reconstruction of functioning human tissues ex vivo is becoming an important
      part of biotechnology. There are compelling scientific, clinical, and
      biotechnological reasons for fully or partially reconstituting human tissues such
      as skin, bone marrow, and liver ex vivo. In particular, bone marrow is a tissue
      of much importance, and there are significant societal and health benefits
      derived from a successfully constructed ex vivo hematopoietic system. In this
      article, we review the current status of this effort. The topics covered include
      the current understanding of the biology of human hematopoiesis, the motivation
      for reconstructing it ex vivo, the current state of ex vivo human hematopoietic
      cultures, the development of important metrics to judge culture performance, and
      an approach based on in vivo mimetics to accomplish this goal. We discuss some
      applications of functional ex vivo hematopoietic cultures and the biological and
      engineering challenges that face research in this area.

PMID- 18613141
TI  - Kinetic study of lipase catalyzed esterification reactions in water-in-oil
      microemulsions.
AB  - The kinetics of the esterification of lauric acid by (-)menthol, catalyzed by
      Penicillium simplicissimum lipase, was studied in water/bis-(2
      ethylhexyl)sulfosuccinate sodium salt (AOT)/isooctane microemulsions. Due to
      their low water content, microemulsions assist in reversing the direction of
      lipase activity, favoring synthetic reactions. The kinetics of this synthesis
      follows a Ping-Pong Bi--Bi mechanism. The values of all apparent kinetic
      parameters were determined. The theoretical model for the expression of enzymic
      activity in reverse micelles, proposed by Verhaert et al. (Verhaert, R.,
      Hilhorst, R., Vermue, M., Schaafsma, T. J., Veeger, C. 1990. Eur. J. Biochem.
      187: 59-72) was extended to express the lipase activity in an esterification
      reaction involving two hydrophobic substrates in microemulsion systems. The model
      takes into account the partitioning of the substrates between the various phases
      and allows the calculation of the intrinsic kinetic constants. The experimental
      results showing the dependence of the initial velocity on the hydration ratio,
      W(o) = [H(2)O]/[AOT], of the reverse micelles, were in accordance with the
      theoretically predicted pattern.

PMID- 18613142
TI  - Activity of mushroom polyphenol oxidase in organic medium.
AB  - A kinetic study of the activity of mushroom polyphenol oxidase in an organic
      system was carried out to obtain detailed enzyme kinetic data in relation to
      optimization of reaction conditions and substrate specificity. A simple method
      for consistent measurement of reaction rates in the heterogeneous enzyme/organic
      solvent system (consisting of immobilized polyphenol oxidase and a hydrated
      solution of the substrate in chloroform) was designed. The aqueous content of the
      system was optimized using p-cresol as the substrate. With this system, a crude
      extract of Agaricus bisporus was used to hydroxylate and oxidize a range of
      selected p-substituted phenolic substrates, yielding o-quinone products.
      Michaelis-Menten kinetics were used to obtain apparent K(M) and V(max) values
      with respect to each of these substrates. Results from this analysis indicated a
      correlation between the enzymic kinetic parameters obtained and the steric
      requirements of the substrates, which could be rationalized in terms of the
      restricted flexibility of the enzyme when it is in chloroform and also in terms
      of substrate and solvent hydrophobicity. In the course of the investigation UV
      molar absorption coefficients of several o-quinones were measured by a novel
      method: (1)H nuclear magnetic resonance (NMR) spectroscopy was employed to
      determine component concentrations in reaction mixtures resulting from the
      transformation of phenols by polyphenol oxidase in chloroform. Thus the UV molar
      absorption coefficients could be obtained directly, avoiding the necessity to
      isolate the water-sensitive, unstable o-quinones.

PMID- 18613143
TI  - Construction and evaluation of a metal ion biosensor.
AB  - Escherichia coli, genetically engineered with a mercury(II)-sensitive promoter
      and the lux genes from Vibrio fischeri, were used as microbial bioluminescent
      sensors for the detection of mercury. Evaluation of this genetic construction was
      carried out by determining the effects of various parameters on cell suspensions
      maintained at constant conditions in a small 100-mL vessel. The strongest light
      intensities and quickest induction times occurred with cells in the
      midexponential growth phase maintained at 28 degrees C, concentrated to 1 x 10(9)
      cells/mL, mixed at very fast speeds, and aerated at 2 vvm (volume of air per
      volume of culture per minute) during light measurement in the small vessel. The
      cells were sensitive to the mercuric ion in the range of 20 nM to 4 microM (4 to
      800 ppb), and the total response time was on the order of 1 hour, depending on
      the above parameters. The cells exhibited great specificity for mercury. The
      cells had almost equal specificity for organic and inorganic forms of the
      mercuric ion and responded more weakly to the mercurous ion. A simple,
      inexpensive, durable miniature probe (3 mL) was constructed and operated using
      the optimum parameters found in the small vessel as a guide. The range of
      sensitivity to the mercuric ion detected in the probe was 10 nM to 4 muM when
      aeration was provided.

PMID- 18613144
TI  - Solvent effects on lipase-catalyzed esterification of glycerol and fatty acids.
AB  - The lipase-catalyzed acylglycerol synthesis with fatty acids of different chain
      length is studied. Measured ester mole fractions at equilibrium are compared with
      calculated mole fractions. For these calculations the computer program TREP (Two
      phase Reaction Equilibrium Prediction) is used. This program is based on the
      UNIFAC group contribution method and is developed for nondilute two-phase
      reaction systems.With one set of equilibrium constants, namely 1.3, 0.8, and 0.6
      for monoester, diester, and triester synthesis, respectively, the equilibrium
      position of the reaction between glycerol and all saturated fatty acids with a
      chain length from 6 to 18 and oleic acid (cis-9-octadecenoic acid) can be
      calculated. Deviations, expressed as the ratio between calculated and measured
      ester mole fractions, usually were between 0.7 and 1.2. In the presence of
      solvents, the deviations of the monoester mole fractions were higher and rose up
      to 3. Without addition of a solvent, the ester mole fractions at equilibrium are
      dependent on the fatty acid chain length. With the short-chain hexanoic acid, the
      monoester mole fraction is the highest ester mole fraction, while for the long
      chain oleic acid, the diester mole fraction is the highest one. The ester mole
      fractions become independent on the chain length of the fatty acid with a solvent
      added in a sufficient high concentration. Both reactions, with saturated and
      unsaturated C(18) fatty acids, lead to the same equilibrium position. The program
      TREP is found to make good predictions of the equilibrium amounts of ester and
      fatty acid. However, systematic deviations arise between measured and calculated
      amounts of water and glycerol in the organic phase. The calculated water and
      glycerol amounts are always lower than the measured ones. These deviations seem
      to be highest in nonpolar media and are probably due to deficiencies in the
      UNIFAC calculation method. Some preliminary experiments show the effect of the
      choice of solvent on the reaction rates. In polar solvents, the monoester
      production rate is enhances by a factor of 1.5 as compared to the reaction rate
      in a system without solvent.

PMID- 18613145
TI  - A numerical analysis of forces exerted by laminar flow on spreading cells in a
      parallel plate flow chamber assay.
AB  - Exposure of spreading anchorage-dependent cells to laminar flow is a common
      technique to measure the strength of cell adhesion. Since cells protrude into the
      flow stream, the force exerted by the fluid on the cells is a function of cell
      shape. To assess the relationship between cell shape and the hydrodynamic force
      on adherent cells, we obtained numerical solutions of the velocity and stress
      fields around bovine aortic endothelial cells during various stages of spreading
      and calculated the force required to detach the cells. Morphometric parameters
      were obtained from light and scanning electron microscopy measurements. Cells
      were assumed to have a constant volume, but the surface area increased during
      spreading until the membrane was stretched taut. Two-dimensional models of steady
      flow were generated using the software packages ANSYS (mesh generation) and FIDAP
      (problem solution). The validity of the numerical results was tested by
      comparison with published results for a semicircle in contact with the surface.
      The drag force and torque were greatest for round cells making initial contact
      with the surface. During spreading, the drag force and torque declined by factors
      of 2 and 20, respectively. The calculated forces and moments were used in
      adhesion models to predict the wall shear stress at which the cells detached.
      Based upon published values for the bond force and receptor number, round cells
      should detach at shear stresses between 2.5 and 6 dyn/cm(2), whereas
      substantially higher stresses are needed to detach spreading and fully spread
      cells. Results from the simulations indicate that (1) the drag force varies
      little with cell shape whereas the torque is very sensitive to cell shape, and
      (2) the increase in the strength of adhesion during spreading is due to increased
      contact area and receptor densities within the contact area.

PMID- 18613146
TI  - Molecular integrity of monoclonal antibodies produced by hybridoma cells in batch
      culture and in continuous-flow culture with integrated product recovery.
AB  - The molecular integrity of monoclonal antibodies (MCAB) produced by murine
      hybridoma cell line TB/C3 was studied in batch and continuous-flow cultures. In
      batch culture, one band of MCAB was detected initially by Western blotting of
      sodium dodecyl sulfate (SDS)-polyacrylamide gels run under unreduced conditions,
      but heterogenous MCAB bands appeared as the culture aged. The latter were due to
      the degradation of MCAB by proteases active at the neutral pH of the culture. The
      deleterious effect of proteases was minimized in the continuous-flow cultures
      which were integrated for product recovery. The MCAB of high quality was purified
      over 26 days from a culture grown at a dilution rate of 0.025 h(-1) (experiment
      1). However, at a lower dilution rate of 0.015 h(-1) (experiment 2), the
      integrity of MCAB was compromised after the initial 13 days of culture. This was
      shown to be due to the variation in the carbohydrate content of MCAB produced, as
      judged by the increased sialylation of heavy chains and the varied reactivity of
      MCAB with lectins (Maackia amurensis agglutinin, Galanthus nivalis agglutinin,
      and Datura stramonium agglutinin) as the age of the culture increased. The
      concentration of the purified MCAB samples by enzyme-linked immunosorbent assay
      (ELISA) (used normally) was usually higher than that estimated by absorbance at
      280 nm. Best correlation between the two methods (ELISA-280 nm ratio of 1.02
      1.25) was obtained with experiment 1 samples. This ratio increased in experiment
      2 and batch culture samples as the heterogeneity of MCAB produced increased,
      being 1.03-2.94 and 2.53-4.62, respectively. Therefore, ELISA overestimated MCAB
      concentration when the molecular integrity of the latter was compromised. The
      ELISA-A(280) nm ratio might hence provide a useful indicator for assessing the
      quality of MCAB produced. Comparison of SDS-polyacrylamide gels stained with
      Coomassie Brilliant Blue R and silver showed that the former correlated better
      with the MCAB activity stain, whereas the silver stained both the protein- and
      carbohydrate-rich components. Comparison of the patterns produced with these two
      stains might therefore offer another parameter to monitor the overall integrity
      of MCAB produced. Finally, the data presented have important implications on the
      validity of using long-term and intensive cultures for generating MCAB because
      such cultures would be subjected to the additive effects reported for batch and
      continuous modes of growth.

PMID- 18613147
TI  - Estimation of disruption of animal cells by turbulent capillary flow.
AB  - Disruption of animal cells in turbulent capillary flows has been predicted from a
      model of cell-hydrodynamic interactions using cell mechanical properties
      determined by micromanipulation. Eddies of sizes similar to or smaller than the
      cells are presumed to interact with those cells, causing local surface
      deformations. The proposed mechanism of cell damage is that such deformations
      result in an increase in membrane tension and surface energy and that a cell
      disrupts when its bursting membrane tension and bursting surface energy are
      exceeded. The surface energy of the cells is estimated from the kinetic energy of
      appropriately sized eddies. To test the model, cells were disrupted in turbulent
      flows in capillaries at mean energy dissipation rates up to 2 x 10(4) m(2)/s(3).
      In all cases the model underestimated the cell disruption by about 15%. Such good
      agreement implies that the approach of the model to the complicated phenomena of
      cell turbulence interactions is reasonable.

PMID- 18613148
TI  - Hydrodynamics and mixing in a multiple air-lift loop reactor.
AB  - A new bioreactor, in which a series of air-lift reactors with an internal loop is
      incorporated into one vessel, is introduced. With this multiple air-lift loop
      reactor (MAL) and approximation of an aerated plug-flow fermentor is strived for.
      Mixing, liquid velocity, and gas hold-up were measured as a function of the gas
      flow rate in this new internal-loop reactor geometry. As a reference,
      hydrodynamics were also investigated in a conventional internal-loop reactor. A
      model description of the hydrodynamics in the second compartment of the MAL is
      given. This model is based on a two-phase, drift-flux model and a friction
      coefficient. Frictional losses were independent of the reactor bottom geometry,
      and were observed to increase with the gas flow rate as a result of the presence
      of stationary gas bubbles in the downcomer. The hydrodynamics and mixing of the
      second MAL compartment were comparable with those of conventional internal-loop
      reactors.

PMID- 18613149
TI  - Activity studies of eight purified cellulases: Specificity, synergism, and
      binding domain effects.
AB  - The activities of six purified Thermomonospora fusca cellulases and Trichoderma
      reesei CBHI and CBHII were determined on filter paper, swollen cellulose, and
      CMC. A simple method to measure the soluble and insoluble reducing sugar products
      from the hydrolysis of filter paper was found to effectively distinguish between
      exocellulases and endocellulases. Endocellulases produced 34% to 50% insoluble
      reducing sugar and exocellulases produced less than 8% insoluble reducing sugar.
      The ability of a wide variety of mixtures of these cellulases to digest 5.2% of a
      filter paper disc in 16 h was measured quantitatively. The specific activities of
      the mixtures varied from 0.41 to 16.31 micromol cellobiose per minute per
      micromole enzyme. The degree of synergism ranged from 0.4 to 7.8. T. reesei CBHII
      and T. fusca E3 were found to be functionally equivalent in mixtures. The
      catalytic domains (cd) of T. fusca endocellulases E2 and E5 were purified and
      found to retain 93% and 100% of their CMC activity, respectively, but neither cd
      protein could digest filter paper to 5.2%. When E2cd and E5cd were substituted in
      synergistic mixtures for the native proteins, the mixtures containing E2cd
      retained 60%, and those containing E5cd retained 94% of the original activity.
      Addition of a beta-glucosidase was found to double the activity of the best
      synergistic mixture. Addition of CBHI to T. fusca crude cellulase increased its
      activity on filter paper 1.7-fold.

PMID- 18613150
TI  - Surfactant-Induced hydrogen production in cyanobacteria.
AB  - Addition of Tween 85 to aqueous suspensions of Anabaena variabilis induced
      photosynthetic evolution of hydrogen over a time span of several weeks: As much
      as 148 nmol H(2)/h . mg dry weight was produced in the first week by a suspension
      containing 4.2 mg dry weight of cells and 77 mM Tween 85. The chemical structure
      of Tween 85 was a necessary prerequisite for inducing hydrogen production, as
      compounds such as Tween 20, 60, and 80 had a quite different effect. There was a
      coupling between photosynthetic oxygen evolution and hydrogen evolution: Hydrogen
      evolution started to be effective only when oxygen evolution subdued. The
      presence of heterocysts in A. variabilis was also required for the Tween-induced
      hydrogen production. Based on these observations, possible mechanisms for the
      photosynthetic effect of Tween 85 are advanced and discussed.

PMID- 18613151
TI  - Sinusoidal endothelial cells prevent rat stellate cell activation and promote
      reversion to quiescence.
AB  - Capillarization precedes hepatic fibrosis. We hypothesize that capillarization of
      sinusoidal endothelial cells (SEC) is permissive for hepatic stellate cell (HSC)
      activation and therefore permissive for fibrosis. We examined whether freshly
      isolated SECs prevent activation of HSCs and promote reversion to quiescence, and
      whether this effect was lost in capillarization. HSCs were cultured alone or co
      cultured with differentiated or capillarized SECs. RESULTS: Co-culture with
      freshly isolated SECs markedly decreased HSC activation after 3 days in culture,
      but co-culture with capillarized SEC had no effect. Inhibition of nitric oxide
      (NO) synthesis abolished SEC suppression of HSC activation. Activated HSCs
      reverted to quiescence when co-cultured with SEC plus vascular endothelial growth
      factor (VEGF) (that is, with SECs that maintained differentiation), but co
      culture with capillarized SECs did not. Reversion of activated HSCs to quiescence
      in the presence of SECs plus VEGF was abolished by inhibition of NO synthesis. To
      establish whether there was indeed reversion, activated and quiescent HSCs were
      counted before and 3 days after adding freshly isolated SECs plus VEGF to
      activated HSCs, and proliferation was quantified in quiescent HSCs; the
      stoichiometry demonstrated reversion. CONCLUSION: Differentiated SECs prevent HSC
      activation and promote reversion of activated HSCs to quiescence through VEGF
      stimulated NO production. Capillarized SECs do not promote HSC quiescence,
      because of loss of VEGF-stimulated NO production.

PMID- 18613153
TI  - The first cis-dioxido uranyl compound under scrutiny.

PMID- 18613152
TI  - The road to non-enzymatic molecular networks.
AB  - This Minireview gives an overview of recent progress in the design and analysis
      of chemical systems that utilize template-directed autocatalytic and cross
      catalytic processes as a means of wiring dynamically interacting molecules.
      Synthetic networks comprising two to nine replicating species are discussed. It
      is shown that for larger systems, more catalytic pathways must be manipulated to
      control the entire network topology and specific functionality of the individual
      species or subnetworks. Cellular biochemistry is an example of a natural
      functional molecular network; synthetic self-organized networks can provide
      additional models of complex systems.

PMID- 18613154
TI  - An integrated self-assembled nanofluidic system for controlled biological
      chemistries.

PMID- 18613155
TI  - Facile and rapid one-step mass preparation of quantum-dot barcodes.

PMID- 18613156
TI  - Conclusive evidence for an S(N)2-Si mechanism in the B(C6F5)3-catalyzed
      hydrosilylation of carbonyl compounds: implications for the related
      hydrogenation.

PMID- 18613157
TI  - Combining the concepts: dual catalysis with carbophilic Lewis acids.

PMID- 18613158
TI  - A concise and flexible synthesis of the potent anti-influenza agents tamiflu and
      tamiphosphor.

PMID- 18613159
TI  - Capitalizing on differing coordination environments and redox potentials to
      prepare an ordered heterobimetallic U(VI)/Np(IV) diphosphonate.

PMID- 18613160
TI  - Construction of titanasiloxanes by incorporation of silanols to the metal oxide
      model [(Ti(eta 5-C5Me5)(mu-O))3(mu3-CR)]: DFT elucidation of the reaction
      mechanism.
AB  - A family of novel titanasiloxanes containing the structural unit ([Ti(eta 5
      C5Me5)O]3) were synthesized by hydron-transfer processes involving reactions with
      equimolecular amounts of mu3-alkylidyne derivatives [(Ti(eta 5-C5Me5)(mu
      O))(3)(mu3-CR)] (R=H (1), Me (2)) and monosilanols, R3'Si(OH), silanediols,
      R2'Si(OH)2, and the silanetriol tBuSi(OH)3. Treatment of 1 and 2 with
      triorganosilanols (R'=Ph, iPr) in hexane affords the new metallasiloxane
      derivatives [(Ti(eta 5-C5Me5)(mu-O))(3)(mu-CHR)(OSiR3')] (R=H, R'=Ph (3), iPr
      (4); R=Me, R'=Ph (5), iPr (6)). Analogous reactions with silanediols, (R'=Ph,
      iPr), give the cyclic titanasiloxanes [(Ti(eta 5-C5Me5)(mu-O))(3)(mu-O2SiR'2)(R)]
      (R=Me, R'=Ph (7), iPr (8); R=Et, R'=Ph (9), iPr (10)). Utilization of tBuSi(OH)3
      with 1 or 2 at room temperature produces the intermediate complexes [(Ti(eta 5
      C5Me5) (mu-O))(3)(mu-O2Si(OH)tBu)(R)] (R=Me (11), Et(12)). Further heating of
      solutions of 11 or 12 affords the same compound with an adamantanoid structure,
      [(Ti(eta 5-C5Me5)(mu-O))3(mu-O3SitBu)] (13) and methane or ethane elimination,
      respectively. The X-ray crystal structures of 3, 4, 6, 8, 10, 12, and 13 have
      been determined. To gain an insight into the mechanism of these reactions, DFT
      calculations have been performed on the incorporation of monosilanols to the
      model complex [(Ti(eta 5-C5H5)(mu-O))3(mu3-CMe)] (2 H). The proposed mechanism
      consists of three steps: 1) hydron transfer from the silanol to one of the oxygen
      atoms of the Ti3O3 ring, forming a titanasiloxane; 2) intramolecular hydron
      migration to the alkylidyne moiety; and 3) a mu-alkylidene ligand rotation to
      give the final product.

PMID- 18613161
TI  - XAS and XMCD investigation of Mn12 monolayers on gold.
AB  - The deposition of Mn(12) single molecule magnets on gold surfaces was studied for
      the first time using combined X-ray absorption spectroscopy (XAS) and X-ray
      magnetic circular dichroism (XMCD) methods at low temperature. The ability of the
      proposed approach to probe the electronic structure and magnetism of Mn(12)
      complexes without significant sample damage was successfully checked on bulk
      samples. Detailed information on the oxidation state and magnetic polarization of
      manganese ions in the adsorbates was obtained from XAS and XMCD spectra,
      respectively. Partial reduction of metal ions to Mn(II) was clearly observed upon
      deposition on Au(111) of two different Mn(12) derivatives bearing 16-acetylthio
      hexadecanoate and 4-(methylthio)benzoate ligands. The average oxidation state, as
      well as the relative proportions of Mn(II), Mn(III) and Mn(IV) species, are
      strongly influenced by the deposition protocol. Furthermore, the local magnetic
      polarizations are significantly decreased as compared with bulk Mn(12) samples.
      The results highlight an utmost redox instability of Mn(12) complexes at gold
      surfaces, presumably accompanied by structural rearrangements, which cannot be
      easily revealed by standard surface analysis based on X-ray photoelectron
      spectroscopy and scanning tunnelling microscopy.

PMID- 18613162
TI  - Solid-phase synthesis of transition-metal complexes.
AB  - This overview highlights recent progress in the field of selective construction
      of linear, oligonuclear transition-metal complexes by using solid-phase synthesis
      procedures. Two general protocols have been identified: formation of coordinative
      bonds between metal centres and bridging ligands and formation of covalent bonds
      between preformed kinetically inert transition-metal-containing building blocks
      in the chain growth step. Currently available suitable building blocks for the
      second approach are based on ferrocene units, bis(terpyridine)-ruthenium(II)
      moieties or metal porphyrins.

PMID- 18613164
TI  - Time-evolving self-organization and autonomous structural adaptation of
      cobalt(II)--organic framework materials with scu and pts nets.

PMID- 18613163
TI  - Enabling continuous-flow chemistry in microstructured devices for pharmaceutical
      and fine-chemical production.
AB  - Microstructured devices offer unique transport capabilities for rapid mixing,
      enhanced heat and mass transfer and can handle small amounts of dangerous or
      unstable materials. The integration of reaction kinetics into fluid dynamics and
      transport phenomena is essential for successful application from process design
      in laboratory to chemical production. Strategies to implement production
      campaigns up to tons of pharmaceutical chemicals are discussed, based on Lonza
      projects.

PMID- 18613165
TI  - Anion binding and luminescent sensing using cationic ruthenium(II) aminopyridine
      complexes.
AB  - The synthesis of a series of ruthenium(II) based anion sensors of the type
      [Ru(eta(6)-C(6)H(4)MeCHMe(2))Cl(L)(2)][BF(4)] (2) is reported in which ligand L
      represents a series of substituted pyridinylmethyl-amine derivatives. The
      carbazole based ligand L(3) exhibits a fluorescent intraligand charge-transfer
      (ILCT) state that is quenched by ligand-to-metal charge transfer (LMCT) upon
      coordination to ruthenium in the 1:1 complex [Ru(eta(6)
      C(6)H(4)MeCHMe(2))Cl(2)(L(3))] (1 c). The 1:2 complex 2 c is fluorescent,
      however, and acts as a fluorescent anion sensor because of the mixing of an anion
      dependent charge-transfer component into the excited state. The 1:2 complexes of
      type 2 all exhibit interesting low symmetry (1)H NMR spectra that also are a
      useful handle on anion complexation. The electronic structures of L(3), 1 c and 2
      c have been probed by time-dependent DFT calculations.

PMID- 18613166
TI  - Self-assembly of L-cysteinato trinuclear cations into metallosupramolecular
      architectures controlled by protons, metal ions, and chirality.

PMID- 18613171
TI  - Synthesis and optical properties of all-trans-oligodiacetylenes.
AB  - A new series of pure and highly soluble oligodiacetylenes (ODAs) was synthesized
      in high yield and on a multi-milligram scale by a sequence of Sonogashira
      reactions with a strongly reduced level of homocoupling. The lambda max and
      epsilon max of these ODAs show an increase with both chain elongation and solvent
      polarity. A plot of lambda max absorption versus 1/CL (CL=conjugation length) was
      shown to be linear. The lambda max converges to 435 nm for the longest members of
      the series at micromolar concentration. This reveals that the longest wavelength
      absorption observed for PDA chains (lambda max up to 700 nm) is due to
      aggregation effects. The fluorescence quantum yield increased from monomer to
      trimer and decreased for longer ODAs. A similar trend is found for the lifetime
      of fluorescence with a maximum of 600 ps for the trimer. The observed linearity
      of the rotational correlation time with the oligomer length implies that the ODA
      chains in solution lack significant geometrical changes. This implies that the
      ODAs in solution are fully stretched molecular rods of up to 4 nm in length.

PMID- 18613172
TI  - Recognition of ionic guests by ionic beta-cyclodextrin derivatives.
AB  - Inclusion compounds of cationic, anionic, and neutral p-substituted derivatives
      of tert-butylbenzene complexed in beta-cyclodextrin and its ionic 6-mono and 6
      hepta derivatives were systematically investigated by isothermal titration
      calorimetry (ITC). All inclusion compounds showed 1:1 stoichiometry with binding
      constants ranging from 10 to 3 x 10(6) M(-1). The binding free energies could be
      subdivided into apolar and electrostatic contributions. The electrostatic
      interactions could be quantitatively described by Coulomb's law by taking into
      account the degree of protonation of hosts and guests, the orientations of the
      guests within the hosts, and ion shielding as described by the Debye-Huckel
      Onsager theory. The orientations of the guests within the cyclodextrin cavities
      were determined by ROESY NMR spectroscopy.

PMID- 18613173
TI  - Helicate extension as a route to molecular wires.
AB  - We describe the preparation of a helicate containing four closely spaced,
      linearly arrayed copper(I) ions. This product may be prepared either directly by
      mixing copper(I) with a set of precursor amine and aldehyde subcomponents, or
      indirectly through the dimerization of a dicopper(I) helicate upon addition of
      1,2-phenylenediamine. A notable feature of this helicate is that its length is
      not limited by the lengths of its precursor subcomponents: each of the two
      ligands wrapped around the four copper(I) centers contains one diamine, two
      dialdehyde, and two monoamine residues. This work thus paves the way for the
      preparation of longer oligo- and polymeric structures. DFT calculations and
      electrochemical measurements indicate a high degree of electronic delocalization
      among the metal ions forming the cores of the structures described herein, which
      may therefore be described as "molecular wires".

PMID- 18613174
TI  - Microsolvation effects on the optical properties of crystal violet.
AB  - We present a joint experimental and theoretical study of the photoabsorption and
      photodissociation behavior of crystal violet, that is, the tris[p
      (dimethylamino)phenyl]methyl cation. The photodissociation spectra of isolated
      and microsolvated crystal violet have been measured. A single band is observed
      for the bare cation. This is in good agreement with the calculated vibronic
      absorption spectrum based on time-dependent density functional theory
      calculations. The interaction of crystal violet with a single water molecule
      shifts and broadens the photodissociation spectrum, so that it approaches the
      spectrum obtained in solution. Theoretical calculations of the structure of the
      complex suggest that the shift in the absorption spectrum originates from a water
      molecule bonding with the central carbon atom of crystal violet.

PMID- 18613175
TI  - Interfering with the sugar code: design and synthesis of oligosaccharide mimics.
AB  - Oligosaccharide determinants of cellular glycoconjugates interact with protein
      receptors triggering a variety of cellular responses within a wide range of
      physiological and pathological processes and with exquisitely tuned selectivity.
      This has led to the formulation of the hypothesis that a sugar code exists and
      that sugar-binding proteins (lectins) act to decipher it and translate it into
      biological responses. Interference with these recognition events by functional
      mimics of carbohydrates could thus be used to modulate or alter signal
      transmission, or to prevent the onset of diseases. Attempts to design and prepare
      glycomimetic inhibitors of well-known target lectins (cholera toxin, DC-SIGN) are
      reviewed in this concept paper.

PMID- 18613177
TI  - Ruthenium-catalyzed oxidative cross-coupling of chelating arenes and
      cycloalkanes.

PMID- 18613176
TI  - Total synthesis of the tetracyclic sesquiterpene (+/-)-punctaporonin C.

PMID- 18613178
TI  - Metal carbene dimerization: versatile approach to polyalkynylethenes.

PMID- 18613180
TI  - Calcium amidoborane hydrogen storage materials: crystal structures of
      decomposition products.

PMID- 18613179
TI  - Highly stereoselective ring expansion reactions mediated by attractive cation-n
      interactions.

PMID- 18613181
TI  - GaI as ligand in transition-metal complexes--an alternative to CO or N2?

PMID- 18613182
TI  - A FACS-based approach to engineering artificial riboswitches.

PMID- 18613183
TI  - Metal-enhanced 1270 nm singlet oxygen phosphorescence.

PMID- 18613184
TI  - Mesoporous silica nanosphere supported ruthenium catalysts for asymmetric
      hydrogenation.

PMID- 18613185
TI  - Incorporation of fluoroacetate into an aromatic polyketide and its influence on
      the mode of cyclization.

PMID- 18613186
TI  - Polarization transfer over the water-protein interface in solids.

PMID- 18613187
TI  - Iridium-catalyzed dehydrocoupling of primary amine-borane adducts: a route to
      high molecular weight polyaminoboranes, boron-nitrogen analogues of polyolefins.

PMID- 18613188
TI  - Convenient synthesis of pyrrolidines by amphiphilic allylation of imines with 2
      methylenepropane-1,3-diols.

PMID- 18613189
TI  - Chemical primer extension in seconds.

PMID- 18613190
TI  - Establishing the chelating alpha-azocarbonyl function in pi-acceptor ligands.

PMID- 18613191
TI  - A hybrid nanoparticle probe for dual-modality positron emission tomography and
      magnetic resonance imaging.

PMID- 18613192
TI  - Hierarchical supramolecular self-assembly of nanotubes and layered sheets.

PMID- 18613193
TI  - Aryl halide tolerated electrophilic amination of arylboronic acids with N
      chloroamides catalyzed by CuCl at room temperature.

PMID- 18613194
TI  - Post-deposition opal evolution.
AB  - The formation of artificial opal films consists of wet opal deposition, drying,
      and possible transformations in the dry state. The processes after deposition,
      before the crystals lattice reaches its final equilibrium state, are studied
      herein. We follow the time evolution of the optical transmission spectra for
      polystyrene opals with different thicknesses. The evolution of the spectra shows
      pronounced changes in the Bragg peak position, width and height, as well as
      changes in the background and, in the beginning of the process, a band related to
      residual water in the sample. Therefore, a wet and a dry phase can be
      distinguished in the opal transformations. They are all connected to shrinkage
      and we associate one of them with a possible new sintering mechanism.

PMID- 18613195
TI  - Structure of pyridazine in the S1 state: experiment and theory.
AB  - The molecular structure of pyridazine in the first electronically excited state
      (S(1)) is deduced from the combined use of resonance-enhanced two-photon
      ionization and mass-analyzed threshold ionization spectroscopic methods. The
      equation-of-motion coupled-cluster single and double (EOM-CCSD) calculation gives
      the distorted planar geometry for the most stable structure of the S(1)
      pyridazine. The symmetry constraint of C(2v) is relaxed to that of C(s), and
      consequently many in-plane vibrational modes are found to be optically active in
      both S(1)-S(0) and D(0)-S(1) excitation spectra, being appropriately assigned
      from the comparison of their frequencies with ab initio values. This indicates
      that the S(1)-S(0) excitation is partially localized, and provides an alternative
      explanation for the long-standing spectroscopic puzzle in S(1) pyridazine.

PMID- 18613196
TI  - Application of static charge transfer within an ionic-liquid force field and its
      effect on structure and dynamics.
AB  - The effects of linear scaling of the atomic charges of a reference potential on
      the structure, dynamics, and energetics of the ionic liquid 1,3
      dimethylimidazolium chloride are investigated. Diffusion coefficients that span
      over four orders of magnitude are observed between the original model and a
      scaled model in which the ionic charges are +/-0.5 e. While the three-dimensional
      structure of the liquid is less affected, the partial radial distribution
      functions change markedly--with the positive result that for ionic charges of +/
      0.7 e, an excellent agreement is observed with ab initio molecular dynamics data.
      Cohesive energy densities calculated from these partial-charge models are also in
      better agreement with those calculated from the ab initio data. We postulate that
      ionic-liquid models in which the ionic charges are assumed to be +/-1 e
      overestimate the intermolecular attractions between ions, which results in
      overstructuring, slow dynamics, and increased cohesive energy densities. The use
      of scaled-charge sets may be of benefit in the simulation of these systems-
      especially when looking at properties beyond liquid structure--thus providing an
      alternative to computationally expensive polarisable force fields.

PMID- 18613197
TI  - Photodissociation spectroscopy of CD3I+ generated by mass-analyzed threshold
      ionization for structure determination.
AB  - A method is devised better to resolve the subbands of the ground vibronic band in
      the mass-analyzed threshold ionization (MATI) spectrum of CD(3)I. By selective
      photodissociation of CD(3)I(+) in these subbands, high-resolution spectra for the
      A(2)A(1)<--X(2)E(3/2) transition are recorded. Spectral analysis confirms our
      previous suggestion that these subbands are due to cations in different
      rotational K states; this demonstrates the capability of MATI to generate
      rovibronically selected ion beams. By using the rotational constants of CH(3)I(+)
      and CD(3)I(+) obtained by spectral analysis, the zero-point-level geometries of
      the cations in the X(2)E(3/2) and A(2)A(1) states are determined. To the best of
      our knowledge, this is the first time that the capability of MATI-PD to determine
      the geometry of a gas-phase polyatomic cation in an excited electronic state is
      demonstrated.

PMID- 18613199
TI  - Photo-induced hydrogen exchange reaction between methanol and glyoxal: formation
      of hydroxyketene.
AB  - We study the structure and photochemistry of the glyoxal-methanol system (G-MeOH)
      by means of FTIR matrix isolation spectroscopy and ab initio calculations. The
      FTIR spectra show that the non-hydrogen-bonded complex, G-MeOH-1, is present in
      an inert environment of solid argon. MP2/aug-cc-pVDZ calculations indicate that G
      MeOH-1 is the most stable complex among the five optimized structures. The
      interaction energy partitioned according to the symmetry-adapted perturbation
      theory (SAPT) scheme demonstrates that the dispersion energy gives a larger
      contribution to the stabilization of a non-hydrogen-bonded G-MeOH-1 complex than
      compared to the hydrogen-bonded ones. The irradiation of G-MeOH-1 with the
      filtered output of a mercury lamp (lambda>370 nm) leads to its photo-conversion
      into the hydroxyketene-methanol complex HK-MeOH-1. The identity of HK-MeOH-1 is
      confirmed by both FTIR spectroscopy and MP2/aug-cc-pVDZ calculations. An
      experiment with deuterated methanol (CH(3)OD) evidences that hydroxyketene is
      formed in a photo-induced hydrogen exchange reaction between glyoxal and
      methanol. The pathway for the photo-conversion of G-MeOH-1 to HK-MeOH-1 is
      studied by a coupled-cluster method [CR-CC(2,3)]. The calculations confirm our
      experimental findings that the reaction proceeds via hydrogen atom exchange
      between the OH group of methanol and CH group of glyoxal.

PMID- 18613198
TI  - Determination of the degree of charge-transfer contributions to surface-enhanced
      Raman spectroscopy.
AB  - We explore the application of a previously suggested formula for determining the
      degree of charge transfer in surface-enhanced Raman scattering (SERS). SERS is
      often described as a phenomenon which obtains its enhancement from three major
      sources, namely the surface plasmon resonance, charge-transfer resonances as well
      as possible molecular resonances. At any chosen excitation wavelength, it is
      possible to obtain contributions from several sources and this has led to
      considerable confusion. The formula for the degree of charge transfer enables one
      to separate these effects, but it requires that spectra be obtained either at two
      or more different excitation wavelengths or as a function of applied potential.
      We apply this formula to several examples, which display rather large charge
      transfer contributions to the spectrum. These are p-aminothiophenol (PATP),
      tetracyano-ethylene (TCNE) and piperidine. In PATP we can show that several lines
      of the same symmetry give the same degree of charge transfer. In TCNE we are able
      to identify the charge-transfer transition, which contributes to the effect, and
      are able to independently determine the degree of charge transfer by wavenumber
      shifts. This enables a comparison of the two techniques of measurement. In
      piperidine, we present an example of molecule to metal charge transfer and show
      that our definition of charge transfer is independent of direction.

PMID- 18613200
TI  - Tunable soret-band splitting of an amphiphilic porphyrin by surface pressure.

PMID- 18613201
TI  - Secondary kinetic isotope effects as probes of environmentally-coupled enzymatic
      hydrogen tunneling reactions.

PMID- 18613202
TI  - Boratabenzene Anions C5B(CN)6(-) and C5B(CF3)6(-) and the superacidic properties
      of their conjugate acids.
AB  - Designing superacids: A computational study of protonated boratabenzenes and the
      gas-phase acidity of their conjugate acids is presented. Conjugate acids of
      boratabenzenes substituted with CN or CF(3) groups (see figure) are highly acidic
      species; the protonated hexacyanoboratabenzene and
      hexakis(trifluoromethyl)boratabenzene have computational gas-phase acidities of
      250.5 and 276.8 kcal mol(-1), respectively.

PMID- 18613204
TI  - Solid-state forms of sodium valproate, active component of the anticonvulsant
      drug epilim.
AB  - The results of the first detailed and systematic investigation of the solid-state
      forms of sodium valproate, one of the most potent and widely used anticonvulsant
      medicines, are presented. By using wet and dry methods, eight solid forms of
      varying stability in air were obtained and characterized. Three extremely
      hygroscopic polycrystalline hydrates, Na(C8H15O2) X H2O (form A), Na(C8H15O2) X
      xH2O (form B), and Na(C8H15O2) X yH2O (form D), three acid-stabilized
      stoichiometric solvates, Na3(C8H15O2)3(C8H16O2)H2O (form C), Na(C8H15O2)(C8H16O2)
      (form E), and Na3(C8H15O2)3(C8H16O2) X 2H2O (form F), the pure anhydrous salt
      Na(C8H15O2) (form H), and an additional unstable thermal intermediate
      Na3(C8H15O2)3(C8H16O2)0.5 (form G) were prepared. Under ambient conditions, forms
      A and B as well as the commercially available compound appear as very hygroscopic
      white powders. Form C is less hygroscopic, while forms E and F are stable and are
      not hygroscopic. Partial stabilization of forms A and B can be achieved by
      evacuation and pressing, which results in a lower hydrate D, or after a heating
      cooling cycle, resulting in crystallization of the anhydrous salt H. Addition of
      one molecule of valproic acid and saturation with one molecule of water of forms
      A and B results in the less hygroscopic form C. Addition to form C of a second
      water molecule affords form F, which is not hygroscopic and is indefinitely
      stable. The symmetric structure and medium alkyl chain length of the valproate
      ion are some of the probable reasons for the presence of a number of solid
      solvates: in its most stable conformation, the valproate ion cannot
      simultaneously pack efficiently and interact strongly through the negatively
      charged carboxylate group without leaving voids in the crystalline lattice. The
      conformational flexibility of the aliphatic chains probably aids the penetration
      of water molecules, which results in a strong affinity for the absorption of
      water.

PMID- 18613203
TI  - Superparamagnetic iron oxide nanoparticle-aptamer bioconjugates for combined
      prostate cancer imaging and therapy.

PMID- 18613205
TI  - The first step into the brain: uptake of NIO-PBCA nanoparticles by endothelial
      cells in vitro and in vivo, and direct evidence for their blood-brain barrier
      permeation.
AB  - By using fluorescent polysorbate 80 coated poly(n-butylcyanoacrylate) (PBCA)
      nanoparticles in an in vivo study, direct evidence was found for the presence of
      nanoparticles entering the brain and retina of rats. The nanoparticles, prepared
      with a miniemulsion process, were labeled in situ with a fluorescent dye and
      coated with polysorbate 80. After preparation the particle size, zeta potential,
      and the molecular weight distribution were determined. BMEC cells were used as an
      in vitro model for the BBB. The cells showed significant uptake of the particles,
      but no transcytosis could be observed in vitro. After applying the particles to
      the animals at two concentrations, cryosections of the brains and retinas were
      prepared. Regarding the sections of the rats that received the lower dose, co
      localization of the applied fluorescent particles and the stained endothelial
      cells could be detected in the brain and retina, indicating particle
      internalization in the endothelial cells. Applied at higher doses, the particles
      could be detected within the brain and retina with few co-localized signals,
      suggesting passage through the blood-brain and blood-retina barriers.

PMID- 18613206
TI  - Titanocene-catalyzed regioselective alkylation of styrenes with grignard reagents
      using beta-bromoethyl ethers, thioethers, or amines.
AB  - Regioselective double alkylation of styrenes with alkyl Grignard reagents and
      alkyl bromides having a heteroatom functional group at the beta-position has been
      achieved by the use of a titanocene catalyst in THF. When ether was used instead
      of THF as a solvent, monoalkylation by substitution of a vinylic hydrogen atom
      with an alkyl group proceeded under similar conditions. These reactions involve
      the addition of alkyl radicals to styrenes to form benzylic radical
      intermediates.

PMID- 18613207
TI  - Highly active and removable ruthenium catalysts for transition-metal-catalyzed
      living radical polymerization: design of ligands and cocatalysts.
AB  - The systematic search and design of phosphine ligands (PR(3)) and amine
      cocatalysts resulted in obtaining pentamethyl-cyclopentadienyl (Cp*)
      ruthenium(II) phosphine complexes [RuCp*Cl(PR(3))(2)], which are highly active
      and removable catalysts, for transition-metal-catalyzed living radical
      polymerization of methyl methacrylate (MMA). The catalysts are conveniently
      prepared in situ from a tetrameric precursor [RuCp*(mu(3)-Cl)](4) and a selected
      phosphine (PR(3)). The combination of the meta-tolyl phosphine [P(m-Tol)(3)]
      ligand and a primary diamine cocatalyst [NH(2)(CH(2))(6)NH(2)] provides a highly
      active catalytic system with precision control of the molecular weight of the
      polymer. The high activity enables a low catalyst dose and a high turn-over
      frequency without deteriorating the controllability. A hydrophilic amine
      cocatalyst (amino alcohol) in place of the diamine, further forms an active and
      removable catalyst; simple treatment with acidic water gave colorless polymers
      visually free from metal residues (>97 % removal; <64 ppm).

PMID- 18613208
TI  - Mono- and dinuclear palladium(II) N,S-heterocyclic carbene complexes with N
      spacers and their Suzuki coupling activities.
AB  - Mixed-ligand N,S-heterocyclic carbene (NSHC) complexes, trans-[PdBr(2)(NSHC)(Py)]
      (NSHC=3-benzyl- or 3-propyl-benzothiazolin-2-ylidene), have been obtained from
      bridge-cleavage reactions of the dinuclear complex, [Pd(mu-Br)Br(NSHC)](2), in
      pyridine at room temperature. Use of neutral N-bidentate donors (L=pyrazine, 1,2
      bis(4-pyridyl)ethane, 4,4'-bipyridine and trans-1,2-bis(4-pyridyl)ethylene)
      yields the dinuclear spacer-bridged [Pd(2)Br(4)(NSHC)(2)(mu-L)] complexes. The X
      ray single-crystal structures of the pyridyl, bridging pyrazine and 1,2-bis(4
      pyridyl)ethane complexes are reported. These air-stable complexes are active in
      the Suzuki-Miyaura coupling reactions of selected aryl bromides. The dinuclear
      complexes are generally more active than their mononuclear pyridyl analogues. The
      benzyl derivatives consistently outperform the n-propyl counterparts.

PMID- 18613209
TI  - Retracted: Integrated specialty mental health care among older minorities
      improves access but not outcomes: results of the PRISMe study.

PMID- 18613210
TI  - A nonparametric smoothing method for assessing GEE models with longitudinal
      binary data.
AB  - Studies involving longitudinal binary responses are widely applied in the health
      and biomedical sciences research and frequently analyzed by generalized
      estimating equations (GEE) method. This article proposes an alternative goodness
      of-fit test based on the nonparametric smoothing approach for assessing the
      adequacy of GEE fitted models, which can be regarded as an extension of the
      goodness-of-fit test of le Cessie and van Houwelingen (Biometrics 1991; 47:1267
      1282). The expectation and approximate variance of the proposed test statistic
      are derived. The asymptotic distribution of the proposed test statistic in terms
      of a scaled chi-squared distribution and the power performance of the proposed
      test are discussed by simulation studies. The testing procedure is demonstrated
      by two real data.

PMID- 18613211
TI  - Comparison of the eating disorder inventory (EDI) in the Netherlands, Austria and
      Italy.
AB  - OBJECTIVE: Comparison of scores of the Eating Disorder Inventory (EDI) in non
      clinical females aged 15-35 years (total n = 2402) in three European countries
      with North-South variation. METHODS: Participants were high school girls from the
      Netherlands (n = 642), Austria (n = 544) and Italy (n = 359), and college
      students from the Netherlands (n = 348), Austria (n = 114) and Italy (n = 395).
      RESULTS: Age-dependent differences of EDI subscale scores were observed. Whereas
      in Dutch females weight and body shape concerns had a peak between 16 and 19
      years, these concerns remained relatively constant in Italy and Austria. The
      Italian scores were significantly higher than the Dutch scores on almost all EDI
      subscales whereby effects were small or medium. CONCLUSIONS: The scores may be
      influenced by socio-cultural factors, cultural traits, culture-specific social
      demands on young adults and differences in maturation between North and South
      Europe. National norms are necessary for different age, weight and sex groups.

PMID- 18613212
TI  - Adapting services for a changing society: a reintegrative model for old age
      psychiatry (based on a model proposed by Knight and Emanuel, 2007).

PMID- 18613213
TI  - Human Vilyuisk encephalitis.
AB  - For more than a century, a type of human encephalomyelitis has been known to
      affect indigenous people in the Sakha Republic in the Vilyui River Valley in
      Russia. The clinical features, laboratory findings, neuropathology, epidemiology
      and search for a causative pathogen are reviewed. One of the agents (Vilyuisk
      human encephalitis virus; VHEV) implicated in Vilyuisk encephalitis, belongs to a
      separate clade of Theiler's murine encephalomyelitis virus (TMEV). The recent
      discovery of theiloviruses from humans and the complete sequence of the VHEV
      raise the possibility that Vilyuisk arose from human cases of Vilyuisk
      encephalitis as a human-TMEV recombinant virus.

PMID- 18613214
TI  - Low-copy episomal vector pFY20 and high-saturation coverage genomic libraries for
      the fission yeast Schizosaccharomyces pombe.
AB  - In fission yeast, as in many organisms, episomally replicating plasmid DNA
      molecules can be used for a wide variety of applications. However, replicating
      plasmids described previously are each propagated at a high copy number per cell.
      Plasmid fission yeast twenty (pFY20) contains the ura4(+) gene for positive and
      negative selection, an origin of replication (ars1) and a stability element
      (stb). Although this plasmid does not have a centromere, it is propagated with a
      copy number of about two plasmids per haploid genome equivalent and it is
      transmitted with relatively high fidelity in mitosis and meiosis. This low-copy
      vector is useful for screens and mutational studies where overexpression (e.g.
      from high copy plasmids) is undesirable. We therefore constructed multiple
      partial-digest, size-fractionated, fission yeast genomic DNA libraries in pFY20
      and in the cloning vector pBluescript KS(+). These libraries have sufficient
      complexity (average of 2100 genome equivalents each) for saturation screening by
      complementation, plasmid shuffle or hybridization.

PMID- 18613215
TI  - Association between serious ischemic cardiac outcomes and medications used to
      treat diabetes.
AB  - PURPOSE: Data on cardiovascular outcomes among treated diabetics have been
      inconsistent. Our goal was to compare cardiovascular outcomes associated with
      different treatments for diabetes. METHODS: This is a retrospective cohort study
      of diabetic patients at least 40 years of age treated in general practices
      participating in The Health Information Network (THIN) data system between 2002
      and 2006. Our primary outcome was serious atherosclerotic vascular disease of the
      heart. RESULTS: Among all diabetics (N = 63 579), the fully adjusted hazard
      ratios of association with our outcome were 1.2 (1.1, 1.3) for insulin, 1.03
      (0.97, 1.09) for sulfonylureas, 0.8 (0.7, 0.8) for biguanide, 1.2 (0.99, 1.5) for
      meglitinide, 0.5 (0.5, 0.6) for thiazolidinediones, and individually 0.6 (0.5,
      0.6) for rosiglitazone, and 0.5 (0.4, 0.7) for pioglitazone. Among those
      individuals newly diagnosed and treated for diabetes after 2002 (N = 13 576), the
      adjusted hazard ratios of association with our outcome were 2.4 (2.0, 2.9) for
      insulin, 1.4 (1.2, 1.7) for sulfonylureas, 0.5 (0.4, 0.5) for biguanide, 0.9
      (0.4, 2.1) for meglitinide, 0.8 (0.7, 1.0) for thiazolidinediones, and
      individually 0.8 (0.6, 1.0) for rosiglitazone, and 0.9 (0.6, 1.4) for
      pioglitazone. Risk increased as total duration of therapy increased for insulin,
      sulfonylureas, and biguanide, but decreased with duration for rosiglitazone and
      pioglitazone. CONCLUSIONS: Overall, insulin was associated with an increased risk
      of myocardial infarction. Its risk increased with longer use, and risk emerged
      with longer use of sulfonylureas and biguanide. Conversely, a protective effect
      emerged with longer use of rosiglitazone or pioglitazone.

PMID- 18613216
TI  - Evaluating assumptions of weighting class methods for partial response using a
      selection model.
AB  - In survey sampling, information about the prevalence of a health outcome Y for a
      defined target population is frequently obtained using a two-stage data
      collection process. In the first stage, households that have members of the
      target population are identified and socio-demographic data that are believed to
      be associated with Y are collected. At the end of the first stage of data
      collection, permission is requested to contact the member's health providers so
      that accurate information about Y can be obtained. When permission is obtained, a
      second phase of data collection is conducted in which those health providers are
      contacted and Y is obtained. A 'complete response' results when data are obtained
      from both the first and the second phases of the survey. A 'partial response'
      results when data are collected from the first phase, but Y is not obtained in
      the second phase. To adjust for selection bias in estimating the prevalence of Y
      caused by partial responders' missing Y values, potential differences between
      complete and partial responders are typically taken into account by using
      weighting class methods. These methods assume that missing Y values are missing
      at random (MAR). This paper describes statistical tests for evaluating whether
      missing data are missing completely at random or MAR.

PMID- 18613217
TI  - Bayesian bootstrap estimation of ROC curve.
AB  - Receiver operating characteristic (ROC) curve is widely applied in measuring
      discriminatory ability of diagnostic or prognostic tests. This makes the ROC
      analysis one of the most active research areas in medical statistics. Many
      parametric and semiparametric estimation methods have been proposed for
      estimating the ROC curve and its functionals. In this paper, we propose the
      Bayesian bootstrap (BB), a fully nonparametric estimation method, for the ROC
      curve and its functionals, such as the area under the curve (AUC). The BB method
      offers a bandwidth-free smoothing approach to the empirical estimate, and gives
      credible bounds. The accuracy of the estimate of the ROC curve in the simulation
      studies is examined by the integrated absolute error. In comparison with other
      existing curve estimation methods, the BB method performs well in terms of
      accuracy, robustness and simplicity. We also propose a procedure based on the BB
      approach to test the binormality assumption.

PMID- 18613218
TI  - Plasma glycooxidation protein products in type 2 diabetic patients with
      nephropathy.
AB  - BACKGROUND: In diabetes mellitus, hyperglycaemia accelerates non-enzymatic
      glycation and oxidative stress leading to damage of macromolecules, among others
      proteins. This manifests in the increased levels of advanced glycation end
      products (AGE) and advanced oxidation protein products (AOPP). OBJECTIVES: To
      assess the plasma levels of AGE and AOPP in the patients with type 2 diabetes
      mellitus (T2DM) and to estimate its relation and connection with the degree of
      nephropathy. MATERIAL AND METHODS: In 121 diabetic patients and 22 healthy people
      plasma levels of AGE and AOPP were determined with fluorimetric and
      spectrophotometric methods, respectively. To estimate nephropathy stage,
      albumin/creatinine ratio was calculated on the basis of albumin and creatinine
      concentrations in early morning urine samples. RESULTS: Diabetic patients had
      significantly higher levels of AGE and AOPP in comparison to healthy people. Both
      parameters were increasing progressively from normoalbuminuria, through
      microalbuminuria to macroalbuminuria. Statistically, the most significant
      differences were observed in AOPP concentration between separated groups. AGE
      fluorescence was significantly different on the same low, statistical level
      between patients with normoalbuminuria when compared to those with micro- and
      macroalbuminuria. Plasma AGE correlated significantly with urinary
      albumin/creatinine ratio whereas AOPP correlated with plasma creatinine level.
      CONCLUSIONS: The connection between plasma levels of both glycooxidation protein
      products-AGE and AOPP with nephropathy severity, measured by the degree of
      albuminuria, in T2DM patients was observed. We can suggest that the AOPP better
      reflect the progression of kidney damage than AGE in examined diabetic patients.

PMID- 18613219
TI  - RNA interfering connective tissue growth factor prevents rat hepatic stellate
      cell activation and extracellular matrix production.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) is a possible key determinant
      of progressive fibrosis. Small interfering RNA (siRNA) is a powerful tool for
      silencing gene expression post-transcriptionally. Therefore, the present study
      aimed to determine whether synthetic siRNA target CTGF down-regulates the
      expression of the CTGF gene in primary rat hepatic stellate cells (HSC) and HSC
      T6, and, furthermore, whether it prevents rat HSC activation and extracellular
      matrix (ECM) production. METHODS: Primary HSC were obtained by enzymatic
      perfusion of rat liver. HSC T6, primary HSC were treated with siRNAs that target
      CTGF or a control siRNA by addition to the culture medium. RESULTS: We obtained
      one siRNA that could sequence-specifically reduce target gene expression by over
      90% at a concentration of 200 nM in the cell culture medium for a total of three
      siRNAs targeting CTGF genes. In HSC T6 cells, the effect of CTGF siRNA was dose
      dependent (50-200 nM) and time-limited to a 24-72-h period. The siRNA knockdown
      of CTGF significantly reduced the expression of alpha-smooth muscle actin
      protein, increased the number of cells, upregulated the ratios of G0/G1 stage in
      rat HSC at 7 days of culture after plating, and attenuated the expression of type
      I and III collagen mRNA with a supernatant concentration of hyaluronic acid, and
      type III procollagen in an activated HSC of culture for 24-72 h. CONCLUSIONS:
      CTGF siRNA could effectively and sequence-specifically down-regulate the
      expression of CTGF in rat HSC, resulting in significant inhibition of HSC
      activation and proliferation as well as ECM production. These findings indicate
      that synthetic siRNA targeting CTGF could prove to be a useful treatment of liver
      fibrosis.

PMID- 18613220
TI  - Prevention of insulin resistance and beta-cell loss by abrogating PKCepsilon
      induced serine phosphorylation of muscle IRS-1 in Psammomys obesus.
AB  - OBJECTIVE: Psammomys obesus gerbil exhibits PKCepsilon over-expression on high
      energy (HE) diet. Muscle insulin receptor (IR) signalling and tyrosine kinase
      activity are inhibited eliciting insulin resistance. We aimed at preventing
      diabetes by inhibiting PKCepsilon-induced serine phosphorylation of IRS-1 with
      novel PKCepsilon abrogating peptides. RESEARCH DESIGN: PKCepsilon abrogating
      peptides were copied from catalytic domain of PKC molecule (PCT patent
      IL2006/000755). Psammomys fed a diabetogenic HE diet received i.p. peptides KCe
      12 and KCe-16 (18 mg/kg) on days 0, 7 and 14 controls received peptide solvent.
      RESULTS: Food consumption and animal weight remained unchanged. On day 16, non
      fasting blood glucose levels returned to normal (90 +/- 5 versus 347 +/- 16 mg/dL
      in untreated controls). Hyperinsulinemia fell from 584 +/- 55 to 180 +/- 22 mU/L.
      Western blot analysis showed that the increased phosphoserine(636, 639) content
      on IRS-1 in gastrocnemius muscle of diabetic animals was reduced three fold, the
      PKB/AKT activity increased two fold and muscle GLUT4 tended to increase, compared
      with controls. Likewise, administration of KCe-12 prior to placing the HE diet
      prevented the onset of diabetes. KCe-12 treatment did not reduce muscle
      PKCepsilon level. Damage and loss of insulin in pancreatic beta cells on HE diet
      were prevented by KCe-12, as shown in micrographs of islet hematoxylin-eosin
      staining and insulin immunostaining. The preserved secretory function enabled
      Psammomys to normalize glucose homeostasis. CONCLUSIONS: KCe-16 and KCe-12
      peptides derived from PKCepsilon substrate-binding region prevented the
      nutritional diabetes and protected muscle IRS-1 from PKCepsilon-induced serine
      phosphorylation, abrogating the insulin-signalling impediment in the Psammomys
      model of type 2 diabetes. Anti-diabetic peptides may lead to novel modalities
      preventing human overnutrition-induced insulin resistance and diabetes.

PMID- 18613221
TI  - Increased renal collagen cross-linking and lipid accumulation in nephropathy of
      Zucker diabetic fatty rats.
AB  - BACKGROUND: Zucker diabetic fatty (ZDF) rat is a genetic model of type 2 diabetes
      and obesity. The mechanism underlying nephropathy in ZDF rats, however, remains
      unclear. METHODS: ZDF rats were compared to age-matched Zucker lean (ZL) rats.
      Physiological and blood biochemical parameters, renal glomerular cross-sectional
      area (hematoxylin-eosin staining), fibrosis (van Giesen staining), collagen
      composition (Sircol Collagen Assay), lipids (enzymatic method) and mRNA
      expression (RT-PCR) were determined. RESULTS: ZDF rats showed an increase in
      renal-insoluble collagen content and the ratio of renal-insoluble to salt-soluble
      collagen (2- and 1.5-fold of the control animals). There were increases in renal
      glomerulosclerosis and interstitial fibrosis in ZDF rats (increased to 2-fold) in
      the glomerular mesangium and tubulointerstitium, and increased glomerular area.
      Renal triglyceride accumulated to greater than 2-fold of those levels in ZL rats.
      These changes were accompanied by hypoalbuminemia, and elevated plasma blood urea
      nitrogen and uric acid levels. Gene profiling showed increased expression of
      transcripts encoding the glomerulosclerotic mediator collagens I and IV,
      plasminogen activator inhibitor-1, transforming growth factor-beta1, and
      angiotensin II type 1 receptor in ZDF rat kidney. Moreover, renal expression of
      mRNAs encoding sterol regulatory element-binding protein-1, a nuclear
      transcription factor that activates genes involved in fatty acid synthesis, and
      acetyl-CoA carboxylase, a key enzyme that mediates fatty acid synthesis, was
      increased in ZDF rats. CONCLUSIONS: Our findings suggest that dysregulated gene
      expression may result in increased renal collagen cross-linking and lipid
      accumulation, that may be associated with development of nephropathy in the
      animal model of type 2 diabetes and obesity.

PMID- 18613222
TI  - Testing for the presence of multiple sources of informative dropout in
      longitudinal data.
AB  - Longitudinal studies tracking the rate of change are subject to patient dropout.
      This dropout process might not only be informative but also heterogeneous in the
      sense that different causes might contribute to multiple patterns of informative
      dropout. We propose a random-effects approach to test for homogeneity of
      informative dropout that accommodates the realistic situation where reasons for
      dropout are not fully understood, or perhaps are even entirely unknown. The
      proposed score test is robust in that it does not depend on the underlying
      distribution of the informative dropout random effects. The test allows for an
      additional level of clustering among participating subjects, as might be found in
      a family study, provided the informative dropout random effects have a known
      correlation structure.

PMID- 18613224
TI  - Predicting impacts of mass-screening policy changes on breast cancer mortality.
AB  - The aim of this study is to present a methodology for taking into account the
      mass-screening invitation data in breast cancer mortality predictions,
      particularly in assessing impacts of screening policy changes on the short-term
      predictions. The methodology is applied to a database that includes observed year
      and age-specific screening invitation schemes in Finnish municipalities from the
      time period 1987-2001. The target year for predictions is 2012. To predict
      mortality, breast cancer incidence and patients' survival from breast cancer are
      modelled with the screening data included. The knowledge of breast cancer
      survival together with the other cause survival is then used to calculate the
      number of breast cancer deaths caused by observed (1987-2001) and predicted (2002
      2012) incident cases in Finland. Survival from breast cancer was estimated with a
      parametric mixture model where the patient population is assumed to be a
      combination of cured and uncured patients. This approach provides a way of
      modelling the hazard of fatal cases and the proportion of cured cases
      simultaneously. In other cause survival, the patients' hazard was allowed to
      differ from that of the general population. Breast cancer mortality predictions
      are presented according to three alternative future scenarios of screening
      policy. The results show no major differences between predictions yielded by
      alternative scenarios: Any policy change would have at the most a 3.0 per cent
      impact on breast cancer mortality in the near future.

PMID- 18613223
TI  - Acute promyelocytic leukaemia and acquired alpha-2-plasmin inhibitor deficiency:
      a retrospective look at the use of epsilon-aminocaproic acid (Amicar) in 30
      patients.
AB  - Bleeding diathesis and a hyper-fibrinolytic state often accompany a diagnosis of
      Acute Promyelocytic Leukaemia (APML). This complication can have grave effects if
      not successfully treated, with a 10-20% incidence of haemorrhagic death. We
      hypothesized that alpha-2-antiplasmin levels would correlate with the risk for
      bleeding, and that administration of epsilon-aminocaproic acid (EACA) would
      attenuate that risk. To assess this, we conducted a retrospective chart review
      analyzing 30 APML patients, 17 of whom were treated with EACA. Thirty patients
      were treated, 21 with primary induction therapy. Patients with low alpha-2
      antiplasmin levels were treated with a coagulopathy protocol consisting of low
      dose heparin, EACA and blood product support. Seventeen patients (57%) developed
      haemorrhagic complications during their treatment. The presence and grade of
      haemorrhage appeared to be associated with the alpha-2-antiplasmin level. There
      were no grade IV haemorrhages or episodes of haemorrhagic death. One episode of
      central venous catheter associated thromboembolism and three deaths from
      infection during chemotherapy were observed. alpha-2-Antiplasmin levels are a
      reliable surrogate for fibrinolysis and haemorrhagic risk in patients with APML.
      Treatment with EACA is a rational way to pharmacologically inhibit fibrinolysis,
      is associated with a low incidence of severe haemorrhagic events, and appears to
      be safe with a low risk of thrombosis. Randomized clinical trials further
      assessing the efficacy and potential toxicity of EACA in inhibiting fibrinolysis
      in patients with APML are needed.

PMID- 18613226
TI  - Comparison of the risk difference, risk ratio and odds ratio scales for
      quantifying the unadjusted intervention effect in cluster randomized trials.
AB  - This paper evaluates methods for unadjusted analyses of binary outcomes in
      cluster randomized trials (CRTs). Under the generalized estimating equations
      (GEE) method the identity, log and logit link functions may be specified to make
      inferences on the risk difference, risk ratio and odds ratio scales,
      respectively. An alternative, 'cluster-level', method applies the t-test to
      summary statistics calculated for each cluster, using proportions, log
      proportions and log odds, to make inferences on the respective scales. Simulation
      was used to estimate the bias of the unadjusted intervention effect estimates and
      confidence interval coverage, generating data sets with different combinations of
      number of clusters, number of participants per cluster, intra-cluster correlation
      coefficient rho and intervention effect. When the identity link was specified,
      GEE had little bias and good coverage, performing slightly better than the log
      and logit link functions. The cluster-level method provided unbiased point
      estimates when proportions were used to summarize the clusters. When the log
      proportion and log odds were used, however, the method often had markedly large
      bias for two reasons: (i) bias in the modified summary statistic used for cluster
      level estimation when a cluster has zero cases with the outcome of interest
      (arising when the number of participants sampled per cluster is small and the
      outcome prevalence is low) and (ii) asymptotically, the method estimates the
      ratio of geometric means of the cluster proportions or odds, respectively,
      between the trial arms rather than the ratio of arithmetic means.

PMID- 18613225
TI  - Incorporating validation subsets into discrete proportional hazards models for
      mismeasured outcomes.
AB  - Standard proportional hazards methods are inappropriate for mismeasured outcomes.
      Previous work has shown that outcome mismeasurement can bias estimation of hazard
      ratios for covariates. We previously developed an adjusted proportional hazards
      method that can produce accurate hazard ratio estimates when outcome measurement
      is either non-sensitive or non-specific. That method requires that mismeasurement
      rates (the sensitivity and specificity of the diagnostic test) are known. Here,
      we develop an approach to handle unknown mismeasurement rates. We consider the
      case where the true failure status is known for a subset of subjects (the
      validation set) until the time of observed failure or censoring. Five methods of
      handling these mismeasured outcomes are described and compared. The first method
      uses only subjects on whom complete data are available (validation subset),
      whereas the second method uses only mismeasured outcomes (naive method). Three
      other methods include available data from both validated and non-validated
      subjects. Through simulation, we show that inclusion of the non-validated
      subjects can improve efficiency relative to use of the complete case data only
      and that inclusion of some true outcomes (the validation subset) can reduce bias
      relative to use of mismeasured outcomes only. We also compare the performance of
      the validation methods proposed using an example data set.

PMID- 18613227
TI  - A maximum likelihood latent variable regression model for multiple informants.
AB  - Studies pertaining to childhood psychopathology often incorporate information
      from multiple sources (or informants). For example, measurement of some factor of
      particular interest might be collected from parents, teachers as well as the
      children being studied. We propose a latent variable modeling framework to
      incorporate multiple informant predictor data. Several related models are
      presented, and likelihood ratio tests are introduced to formally compare fit. The
      incorporation of partially observed subjects is addressed under a variety of
      missing data mechanisms. The methods are motivated by and applied to a study of
      the association of chronic exposure to violence on asthma in children.

PMID- 18613229
TI  - Engineering cellulase mixtures by varying the mole fraction of Thermomonospora
      fusca E5 and E3, Trichoderma reesei CBHI, and Caldocellum saccharolyticum beta
      glucosidase.
AB  - In this study, different mole fractions of pure Thermomonospora fusca E(5) and
      E(3), plus Trichoderma reesei CBHI were studied for reducing sugar production at
      2 h, degree of synergism, and cellulose binding. In addition, the effects of
      introducing the Caldocellum saccharolyticum beta-glucosidase into this cellulase
      system were investigated. The cellulases used were purified to homogeneity.
      Avicel PH 102 (4% w/w solution in 0.05 sodium acetate pH 5.5 buffer) was the
      substrate. Reactions were run at 50 degrees C for 2 h using total cellulase
      concentrations of 8.3 or 12.2 microM. A bimixture of T. fusca E(3) and T. reesei
      CBHI was very effective in hydrolyzing microcrystalline cellulose (9.1%
      conversion). The addition of endoglucanase E(5) to the mixture only increased
      conversion to 9.8%. However, when both E(5) and beta-glucosidase were added,
      conversion increased to 14%. It was also observed that increasing total cellulase
      concentration beyond 8.3 muM did little to increase percent conversion of
      cellulose into glucose. The results of the binding studies indicate no
      competition for binding sites between the endo- and exocellulases.

PMID- 18613230
TI  - Temperature control of growth and productivity in mutant Chinese hamster ovary
      cells synthesizing a recombinant protein.
AB  - The use of a temperature switch to control the growth and productivity of
      temperature-sensitive (ts) mutants was investigated to extend the productive life
      span of recombinant Chinese hamster ovary (CHO) cells in batch culture.
      Bromodeoxyuridine was used at 39 degrees C to select mutagenized CHO-K1 cells,
      which resulted in the isolation of 31 temperature-sensitive mutants that were
      growth inhibited at 39 degrees C. Two of these mutants were successfully
      transfected with the gene for tissue inhibitor of metalloproteinases (TIMP) using
      glutamine synthetase amplification, and a permanent recombinant cell line
      established (5G1-B1) that maintains the ts phenotype.Continuous exposure to the
      nonpermissive temperature (npt) of 39 degrees C led to a rapid decline in cell
      viability. However, a temperature regime using alternating incubations at 34
      degrees C and 39 degrees C arrested the 5G1-B1 cells while retaining a high cell
      viability for up to 170 h in culture. The specific production rate of the growth
      arrested cells was 3-4 times that of control cultures maintained at a constant 34
      degrees C over the crucial 72-130-h period of culture, which resulted in a 35%
      increase in the maximum product yield. Glucose uptake and lactate production both
      decreased in arrested cells. Flow cytometric analysis indicated that 5G1-B1 cells
      arrested in the G(1) or G(0) phase of the cell cycle, and no major structural
      damage was caused to these cells by the alternating temperature regime.These
      results demonstrate that growth-arrested ts CHO cells have increased productivity
      compared to growing cultures and maintain viability for longer periods. The
      system offers the prospect of enhancing the productivity of recombinant mammalian
      cells grown in simple batch fermentors.

PMID- 18613231
TI  - Immobilization of glucose oxidase in thin polypyrrole films: influence of
      polymerization conditions and film thickness on the activity and stability of the
      immobilized enzyme.
AB  - Using monomers that polymerize to form electrically conducting polymers, one can
      control the thickness of the polymer film and the amount of enzyme that can be
      immobilized in the films. First, an investigation of the major variables that
      influence the immobilization of glucose oxidase by entrapment in polypyrrole
      films, prepared by electropolymerization from aqueous solutions containing the
      enzyme and monomer, was carried out. Then the optimized conditions were used to
      assess the effects of film thickness on the activity and stability of immobilized
      enzyme. For the films ranged in thickness from 0.1 microm to 1.6 microm, the
      resulting apparent activity and stability of the immobilized enzyme were found to
      be a strong function of the polymer film thickness. Above a thickness of 1.0
      microm, the apparent activity of the immobilized enzyme increases linearly with
      increasing film thickness. The nonlinearity observed for films of thickness less
      than 1.0 microm can be attributed to the changes observed in the morphology of
      the resulting polypyrrole films. Furthermore, it was noted that when the glucose
      oxidase/polypyrrole films are stored in phosphate buffer, at 4 degrees C, the
      observed rate of loss in apparent activity of the immobilized enzyme is highest
      for the first few days, also being higher for the thinner films. However, after
      the loosely entrapped enzyme is leached from the polymer film, the rate of loss
      in activity is very low indicating that the well-entrapped enzyme, as well as the
      polypyrrole films, exhibit good stability. Finally, the reproducibility of the
      immobilization technique is excellent.

PMID- 18613232
TI  - Correlation of Aspergillus niger broth rheological properties with biomass
      concentration and the shape of mycelial aggregates.
AB  - Aspergillus niger was grown in a 7-L chemostat at biomass levels of 7 to 9 gL(
      1); dilution rates of 0.03, 0.05, 0.075, and 0.009 h(-1); and dissolved oxygen
      tensions of 7%, 12%, and 40% of air saturation. Broth rheological measurements
      were made on-line, while off-line image analysis was used to measure mycelial
      morphology, including characterization of mycelial aggregates (clumps). Under all
      conditions, more than 87% of the hyphase were in clumps, the shape of which
      determined the rheological characteristics of the broth. In particular, the power
      law consistency index could be correlated with the biomass concentration and the
      roughness factor of the clumps, which describes their hairiness. A decrease in
      specific growth rate decreased roughness, possibly due to changes in the amount
      of clump breakup. However, decreases of roughness with increasing dissolved
      oxygen tension might rather imply some effect on hyphal-hyphal interactions
      within the clumps.

PMID- 18613233
TI  - Metabolic engineering of Clostridium acetobutylicum ATCC 824 for increased
      solvent production by enhancement of acetone formation enzyme activities using a
      synthetic acetone operon.
AB  - The ability to genetically alter the product-formation capabilities of
      Clostridium acetobutylicum is necessary for continued progress toward industrial
      production of the solvents butanol and acetone by fermentation. Batch
      fermentations at pH 4.5, 5.5, or 6.5 were conducted using C. acetobutylicum ATCC
      824 (pFNK6). Plasmid pFNK6 contains a synthetic operon (the "ace operon") in
      which the three homologous acetone-formation genas (adc, ctfA, and ctfB) are
      transcribed from the adc promoter. The corresponding enzymes (acetoacetate
      decarboxylase and CoA-transferase) were best expressed in pH 4.5 fermentations.
      However, the highest levels of solvents were attained at pH 5.5. Relative to the
      plasmid-free control strain at pH 5.5, ATCC 824 (pFNK6) produced 95%, 37%, and
      90% higher final concentrations of acetone, butanol, and ethanol, respectively; a
      50% higher yield (g/g) of solvents on glucose; and a 22-fold lower mass of
      residual carboxylic acids. At all pH values, the acetone-formation enzymes were
      expressed earlier with ATCC 824 (pFNK6) than in control fermentations, leading to
      earlier induction of acetone formation. Furthermore, strain ATCC 824 (pFNK6)
      produced butanol significantly earlier in the fermentation and produced
      significant levels of solvents at pH 6.5. Only trace levels of solvents were
      produced by strain ATCC 824 at pH 6.5. Compared with ATCC 824, a plasmid-control
      strain containing a vector without the ace operon also produced higher levels of
      solvents [although lower than those of strain ATCC 824 (pFNK6)] and lower levels
      of acids. Strains containing plasmid-borne derivatives of the ace operon, in
      which either the acetoacetate decarboxylase or CoA-transferase alone were
      expressed at elevated levels, produced acids and solvents at levels similar to
      those of the plasmid-control strain.

PMID- 18613234
TI  - Effect of shear on the inactivation kinetics of the enzyme dextransucrase.
AB  - An inactivation model previously developed to characterize the rate of enzyme
      activity loss in unstirred solutions was extended to take into account
      orthokinetic interactions resulting from convective mixing. A synergistic
      relationship between shear rate and temperature was observed; the rate of
      inactivation of the enzyme dextransucrase was unaffected by the action of shear
      below 25 degrees C, but was increased by the shear rate at 30 degrees C. Shear
      rate does not appear to influence the equilibrium between native and denatured
      dextransucrase either directly in solution or indirectly by augmenting the
      turnover of the gas-liquid interface. However, a second-order plot of the inverse
      of relative activity (A(O)/A) versus Gt (shear rate x time) of dextransucrase at
      a constant temperature was linear because of the influence of shear on the
      coagulation of the denatured enzyme. The addition of 0.01 g L(-1) of polyethylene
      glycol (MW 20,000) blocked this coagulation reaction, thereby completely
      inhibiting the shear-induced inactivation of dextransucrase at 30 degrees C.

PMID- 18613235
TI  - A simple model for the optimization of the extraction yield of antibiotics
      isolated from fermented broths by direct crystallization.
AB  - This article is concerned with the development of a model to maximize the overall
      yield of isolation of antibiotics recovered from fermented broths by the so
      called direct precipitation method. In this process, as in most antibiotics
      isolation processes, a second filtration of the semiexhaust mycellium from the
      first filtration, after slurrying it in water at the suitable pH, is required.
      The maximization of the overall yield of isolation implies the use of an optimal
      amount of water, measured as a volume to fermented broth mass ratio, which can be
      calculated by using the model derived here. The model also allows for the
      calculation of the partial and overall yields of the isolation process, and its
      validity is demonstrated by its ability to describe reasonably well the isolation
      data of two different tetracycline-fermented broths produced according to two
      different technologies.The application of the model requires only the knowledge
      of easily obtainable fermented broth parameters and is illustrated for two
      different types of tetracycline-fermented broths. Although the model had been
      derived for the optimization of the overall yield of isolation of antibiotics
      recovered by direct precipitation, it can easily be adapted to be used for the
      optimization of the overall yield of isolation of antibiotics recovered by other
      isolation processes.

PMID- 18613236
TI  - The effect of the dilution rate on CHO cell physiology and recombinant interferon
      gamma production in glucose-limited chemostat culture.
AB  - The physiology of a recombinant Chinese hamster ovary cell line in glucose
      limited chemostat culture was studied over a range of dilution rates (D = 0.008
      to 0.20 h(-1)). The specific growth rate (micro) deviated from D at low dilution
      rates due to an increased specific death rate. Extrapolation of these data
      suggested a minimum specific growth rate of 0.011 h(-1) (micro(max) = 0.025 h(
      1)) The metabolism at each steady state was characterized by determining the
      metabolic quotients for glucose, lactate, ammonia, amino acids, and interferon
      gamma (IFN-gamma). The specific rate of glucose uptake increased linearly with
      mu, and the saturation constant for glucose (K(s)) was calculated to be 59.6
      microM. There was a linear increase in the rate of lactate production with a
      higher yield of lactate from glucose at high growth rates. The decline in the
      rate of production of lactate, alanine, and serine at low growth rate was
      consistent with the limitation of the glycolytic pathway by glucose. The specific
      rate of IFN-gamma production increased with mu in a manner indicative of a growth
      related product. Despite changes in the IFN-gamma production rate and cell
      physiology, the pattern of IFN-gamma glycosylation was similar at all except the
      lowest growth rates where there was increased production of nonglycosylated IFN
      gamma.

PMID- 18613237
TI  - Study on separation of conalbumin and lysozyme from high concentration fresh egg
      white at high flow rates by a novel ion-exchanger.
AB  - In this report, we show that it is possible to separate valuable proteins from
      egg-white using a Productiv(TM) CM ion-exchanger column operated at flow rates
      significantly higher than those than can be achieved using traditional
      particulate adsorbents. In the approach taken, sample pretreatment is restricted
      to a simple dilution of the egg-white, which can then be applied to the column at
      superficial velocities (V(s)) of up to 13.8 m/h. Under a loading of 220 mg total
      protein per milliliter of ion-exchanger, the resolution (R(s)) between the eluted
      conalbumin and lysozyme fractions was found to be almost constant during nine
      consecutive adsorption/desorption cycles. For all nine consecutive batches, the
      column average adsorption capacity was greater than 30 mg/mL, with 90% recovery
      of adsorbed protein being achieved in each run. The overall productivity achieved
      was 12.6 kg/m(3) h for lysozyme and 31.2 kg/m(3) h for conalbumin.

PMID- 18613238
TI  - Production of propionic acid from whey permeate by sequential fermentation,
      ultrafiltration, and cell recycling.
AB  - This article deals with the production by fermentation of a mycostatic and
      aromatic food additive based on propionic acid. Membrane bioreactors have been
      used from laboratory scale up to pilot and industrial production plants. Due to
      the high cell densities achieved by the sequential recycling mode of operation, a
      mixed acids solution was rapidly produced from whey permeate. The sterile
      fermented broth obtained was subsequently concentrated at different levels by
      evaporation and spray drying according to the projected use. Concentrated
      Propionibacterium cells (200 g x L(-1) DW) were obtained from the process by
      periodic bleeds and could be used to good effect as cheese starters, silage
      preservatives, or probiotics. Propionic acid concentrations from 30 to 40 g x L(
      1) were easily achieved with no residual lactose. The highest volumetric
      productivity was 1.6 g x L(-1) x h(-1) for total acid and 1.2 g x L(-1) x h(-1)
      for propionic acid with a specific productivity of 0.035 h(-1).

PMID- 18613239
TI  - Protein adsorption in polysulfone hollow fiber bioreactors used for serum-free
      mammalian cell culture.
AB  - The recovery of serum-free medium proteins from poly-sulfone hollow fiber
      bioreactors (HFBRs) was investigated. More than 99% of the initial transferrin
      was adsorbed to the hydrophobic hollow fibers within 2 h of HFBR operation. A
      methodology to minimize transferrin adsorption by pre-adsorption of bovine serum
      albumin (BSA) was developed. BSA adsorption on suspended cut fibers was virtually
      complete within 1 h. BSA-coated fibers adsorbed only 5% of the transferrin within
      10 days, whereas uncoated cut fibers adsorbed more than 99% of the transferrin
      within 1 h. An improved HFBR startup procedure, using a BSA-coating step before
      inoculation, resulted in substantially higher transferrin recovery. Additional
      factors influenced extracapillary space (ECS) transferrin concentrations.
      Pronounced downstream polarization of transferrin was observed in the ECS. In
      addition, the 30-kDa nominal molecular weight cutoff ultrafiltration membranes
      rapidly leaked transferrin from the ECS to the lumen.

PMID- 18613240
TI  - Production of Bacillus thuringiensis spores in total cell retention culture and
      two-stage continuous culture using an internal ceramic filter system.
AB  - The production of Bacillus thuringiensis spores was investigated in a bioreactor
      incorporating a ceramic membrane filter to improve spore concentration and
      volumetric productivity. Two cultivation methods were used in this study: a total
      cell retention culture (TCRC), and a two-stage continuous culture with partial
      cell bleeding. In the TCRC, fed by 50 g/L of glucose, a spore concentration of
      1.6 x 10(10) CFU/mL was obtained with a spore percentage of greater than 95% and
      a maximum cell mass of 82.2 g/L. The volumetric productivity was four times
      higher than that obtained from batch cultivation. In the two-stage continuous
      culture with partial cell bleeding spore concentration was strongly dependent on
      the bleed ratio. The spore concentration of 1.8 x 10(9) CFU/mL and the spore
      percentage of 70% were obtained at the second stage when a bleed ratio of 0.33
      and a dilution rate of 0.23 h(-1) were used.

PMID- 18613241
TI  - Foreign gene expression (beta-galactosidase) during the cell cycle phases in
      recombinant CHO cells.
AB  - Recombinant mammalian cultures for heterologous gene expression typically involve
      cells traversing the cell cycle. Studies were conducted to characterize rates of
      accumulation of intracellular foreign protein in single cells during the cell
      cycle of Chinese hamster ovary (CHO) cells transfected with an expression vector
      containing the gene for dihydrofolate reductase (dhfr) and the lacZ gene for
      bacterial beta-galactosidase (a nonsecreated protein). The lacZ gene was under
      the control of the constitutive cytomegalovirus promoter. These normally
      attachment-grown cells were adapted to suspension culture in 10(-7) M
      methotrexate, and a dual-laser flow cytometer was used to simultaneously
      determine the DNA and foreign protein (beta-galactosidase) content of single
      living cells. Expression of beta-galactosidase as a function of cell cycle phase
      was evaluated for cells in the exponential growth phase, early plateau phase, and
      inhibited traverse of the cell cycle during exponential growth. The results
      showed that the beta-galactosidase production rate is higher in the S phase than
      that in the G1 or G2/M phases. Also, when cell cycle progression was stopped at
      the S phase by addition of aphidicolin, beta-galactosidase content in single
      cells was higher than that in exponential phase or plateau phase cells and
      increased with increasing culture time. Although the cells did not continue to
      divide after aphidicolin addition, the production of beta-galactosidase per unit
      volume of culture was very similar to that in normal exponential growth.

PMID- 18613242
TI  - Comments on "In search of a thermodynamic description of biomass yields for the
      chemotrophic growth of microorganisms".
AB  - In a recent publication, Heijnen and van Dijken (Biotechnol. Bioeng. 39: 833-858,
      1992) reviewed the state of the art regarding the use of macroscopic methods in
      the correlation of biomass yields in growing microorganisms. In their article,
      reference is made to this author's work of some 10 years ago.Heijnen and van
      Dijken introduce the Gibbs' energy dissipation as a concept with favorable
      characteristics compared with various other approaches, including thermodynamic
      efficiency, as introduced by this author.In this communication, it will be shown
      that the "dissipation" and the "thermodynamic efficiency" description are
      completely equivalent and that there can be no preference for one of these in
      terms of rigor or characteristics.

PMID- 18613244
TI  - Stability of antibody productivity is improved when hybridoma cells are entrapped
      in calcium alginate beads.
AB  - Loss of monoclonal antibody (MAb) productivity in long-term, free-suspended cell
      culture is often attributed to the appearance of a nonproducing population of
      hybridoma cell (NP) in the culture which has a growth advantage over the
      producing population (P). However, when an NP appears in long-term culture of
      entrapped cells, it may not be able to take over the whole culture in a short
      period of time due to the limited growth of the entrapped cells. In order to
      examine the hypothesis that entrapped cells can have improved stability of MAb
      productivity due to limited cell growth, free-suspended cell culture and calcium
      alginate-entrapped cell culture with inocula consisting of a P and an NP were
      compared with regard to stability of MAb productivity in a repeated fed-batch
      culture. In free-suspended cell culture, the NP appeared to take over the whole
      culture within three batches, and thereby MAb production completely disappeared.
      In entrapped cell culture, an NP appeared to outgrow the P rapidly only during an
      exponential growth phase, resulting in a significant decrease in specific MAb
      productivity, q(MAb), from 11.58 microg/10(6) cell/day to 2.76 microg/10(6)
      cell/day. However, when the cell growth was limited in entrapped cell culture,
      the NP no longer outgrew the P rapidly, as indicated by the stable value of
      q(MAb). In addition, when the cells recovered from the alginate beads by citrate
      buffer treatment were subcultured in free-suspended cell culture, MAb production
      rapidly deteriorated and completely disappeared within two batches. Thus, the P
      present at a small fraction of viable cell concentration in the beginning of the
      free-suspended cell culture, which were previously entrapped in alginate beads,
      seemed to be outgrown rapidly by the NP. Taken together, the results obtained
      from these experiments support the hypothesis that the limited cell growth in
      entrapped cell culture, which keeps an NP from taking over the whole culture, is
      responsible, in part, for the improved stability of MAb productivity.

PMID- 18613245
TI  - Estimation of risk factor associations when the response is influenced by
      medication use: an imputation approach.
AB  - When the outcome of interest is a quantity whose value may be altered through the
      use of medications, estimation of associations with this outcome is a challenging
      statistical problem. For participants taking medication the treated value is
      observed, but the underlying 'untreated' value may be the measure that is truly
      of interest. Problematically, those with the highest untreated values may have
      some of the lowest observed measurements due to the effectiveness of medications.
      In this paper we propose an approach in which we parametrically estimate the
      underlying untreated variable of interest as a function of the observed treated
      value, and dose and type of medication. Multiple imputation is used to
      incorporate the variability induced by the estimation. We show that this approach
      yields more realistic parameter estimates than other more traditional approaches
      to the problem and that study conclusions may be altered in a meaningful way by
      using the imputed values.

PMID- 18613246
TI  - Marginalized models for longitudinal ordinal data with application to quality of
      life studies.
AB  - Random effects are often used in generalized linear models to explain the serial
      dependence for longitudinal categorical data. Marginalized random effects models
      (MREMs) for the analysis of longitudinal binary data have been proposed to permit
      likelihood-based estimation of marginal regression parameters. In this paper, we
      propose a model to extend the MREM to accommodate longitudinal ordinal data.
      Maximum marginal likelihood estimation is proposed utilizing quasi-Newton
      algorithms with Monte Carlo integration of the random effects. Our approach is
      applied to analyze the quality of life data from a recent colorectal cancer
      clinical trial. Dropout occurs at a high rate and is often due to tumor
      progression or death. To deal with events due to progression/death, we used a
      mixture model for the joint distribution of longitudinal measures and
      progression/death times and use principal stratification to draw causal
      inferences about survivors.

PMID- 18613247
TI  - Determinants of burden in those who care for someone with dementia.
AB  - OBJECTIVES: Caregiver burden is a key measure in caregiver research and is
      frequently used as a baseline measure in intervention studies. Previous research
      has found numerous factors associated with caregiver burden such as the
      relationship quality between carer and patient, the patient's cognitive ability,
      behavioural and psychological symptoms displayed by the patient, caregiver
      gender, adverse life events to name a few. Many studies have investigated these
      factors singularly however current thought suggests a multi-factorial role and
      inter-dependence of these factors. Based on this it was decided to investigate
      factors associated with caregiver burden using a multiple regression analysis in
      order to ascertain the predictive quality of these factors of caregiver burden.
      METHOD: Cross-sectional study using validated measures of a patient's cognitive
      ability, ability to carry out day-to-day tasks and behavioural and psychological
      symptoms. Caregiver outcomes used are caregiver burden, relationship quality,
      caregiver confidence, experience of adverse life events, neuroticism, age and
      gender. Interviews and questionnaires were carried out on 74 patients diagnosed
      with dementia and their main caregivers from the Midlands of England. RESULTS:
      Multiple regression analysis showed that caregiver overload, carer-patient
      relationship quality, the experience of adverse life events, caregiver gender,
      caregivers' level of neuroticism, caregiver role captivity and the level of
      caregiver confidence accounted for over 80% of the variance in caregiver burden.
      CONCLUSION: These results confirm previous correlational research on caregiver
      burden. Furthermore, due to the use of multiple regression analysis the findings
      also show factors that are clear predictors of caregiver burden and we offer
      possible suggestions from these findings on future clinical practice
      interventions on caregiver burden.

PMID- 18613248
TI  - Clinical manifestations and beta cell function in Swedish diabetic children have
      remained unchanged during the last 25 years.
AB  - BACKGROUND: The incidence of type 1 diabetes in childhood has doubled in Sweden
      during the last decades. Environmental factors may cause a different disease
      process, residual beta cell function and clinical manifestation. Insulin therapy
      has become more intensive. The aim of this study was to examine the clinical
      characteristics at onset, C-peptide secretion during the first years after
      diagnosis and if there was any secular trends during the last 25 years. METHODS:
      All 316 children diagnosed with type 1 diabetes during 1976--2000 and living in
      the Linkoping area were included. Information about clinical characteristics at
      diagnosis, duration of partial remission, insulin therapy at diagnosis and during
      the first years was collected from medical records. C-peptide secretion (fasting
      and stimulated) was measured regularly during the first 5 years. For analysis,
      the population was divided in five cohorts according to the year of diagnosis.
      RESULTS: The clinical characteristics at onset were unchanged as well as duration
      of partial remission. C-peptide secretion was highest after 3 months and then
      declined gradually. After 5 years 32.7% of the patients had measurable fasting C
      peptide, but only 6.5% > 0.1 nmol/L. HbA1c and insulin doses were lower in
      patients with persistent fasting C-peptide secretion > 0.1 nmol/L. The cohort
      1996--2000 had higher stimulated C-peptide secretion at diagnosis and at 3
      months, after longer follow-up there was no difference. CONCLUSION: The clinical
      characteristics at diagnosis, partial remission and duration of C-peptide
      secretion have remained largely unchanged for the last 25 years.

PMID- 18613249
TI  - Syncope and sinus bradycardia from combined use of thalidomide and beta-blocker.
AB  - We present a case of a 76-year-old Japanese man with hypertension and multiple
      myeloma (MM) presented with syncope and sinus bradycardia. Thalidomide therapy
      for MM was added to longstanding atenolol therapy one month prior to
      presentation. His heart rate (HR) was around 70 beats per minute (bpm) before
      addition of Thalidomide. His HR on presentation was less than 30 bpm. He was
      treated with intravenous atropine followed by temporary pacemaker and taken off
      atenolol. His HR returned to around 70 bpm few days after discontinuation of
      atenolol, even though he was still taking thalidomide, permitting outpatient
      management without a pacemaker. Both thalidomide and atenolol have been reported
      to cause bradycardia. Neither agent caused bradycardia when used alone in this
      patient, but simultaneous use caused symptomatic bradycardia. As thalidomide is
      prescribed more frequently, clinicians should be aware of the possibility of drug
      induced sinus bradycardia due to the interaction of thalidomide and beta
      blockers.

PMID- 18613250
TI  - Short-echo spectroscopic imaging combined with lactate editing in a single scan.
AB  - A short-echo spectroscopic imaging sequence extended with a frequency-selective
      multiple-quantum- coherence technique (Sel-MQC) is presented. The method enables
      acquisition of a complete water-suppressed proton spectrum with a short echo time
      and filtering of the J-coupling metabolite, lactate, from co-resonant lipids in
      one scan. The purpose of the study was to validate this combined pulse sequence
      in vitro and in vivo. Measurements on phantoms confirmed the feasibility of the
      method, and, for a practical in vivo application, experiments were carried out on
      eight tumors from two different tumor models [UT-SCC-8 (n = 4) and SAS (n = 4)].
      T(1)- and T(2)-weighted metabolite and lipid ratios were calculated, and the
      tumors showed different values in the central and outer regions. The ratio of the
      lipid methylene peak area (1.30 ppm) to choline peak area (3.20 ppm) was
      significantly (p < 0.01) different in the central tumor area between the two
      models, and lactate was detected in only three out of four tumors in the SAS
      tumor line. The present approach of combining short-echo spectroscopic imaging
      and lactate editing allows the characterization of tumor-specific metabolites
      such as choline, lipid methylene and methyl resonances as well as lactate in a
      single scan.

PMID- 18613251
TI  - Empirical estimation of life expectancy from large clinical trials: use of left
      truncated, right-censored survival analysis methodology.
AB  - In the current era of ever-increasing health care costs, economic analyses are an
      essential component in the comprehensive evaluation of new medical interventions.
      Cost-effectiveness analysis (CEA)--the most common form of economic analysis used
      in medicine--aids policy-makers in determining how to allocate finite health care
      dollars among possible alternative therapies. CEA relates the incremental
      benefits of a new technology to its incremental costs in a cost-effectiveness
      (CE) ratio. Although the generally agreed-upon standard of presentation for the
      CE ratio is the lifetime perspective (incremental lifetime cost to add one life
      year), this perspective presents an obvious challenge to the statistical analyst.
      Most large clinical trials collect limited follow-up data, and yet their findings
      form the basis of therapeutic recommendations that often extend far beyond the
      limits of the empirical data. Although clinical practice guidelines do not yet
      require explicit modeling to examine the long-term implications of their
      recommendations, health policy analyses routinely rely upon such extrapolations.
      This paper describes methods for using empirical patient-level data to
      extrapolate survival in large clinical trials and cohorts beyond a limited follow
      up period in which most patients remain alive in order to estimate the entire
      survival distribution for a cohort of patients. We accomplish this task through a
      novel combination of models that estimate the hazard rate not only as a function
      of time but also as a function of patient age. Extrapolation of survival beyond a
      limited time frame is made possible by capitalizing on the extensive latitude of
      survival information available across the range of ages represented in the data.
      Variations in approach are presented, and issues arising in these analyses are
      discussed. The proposed methodology is developed, applied, and evaluated in both
      a large clinical trial cohort with 5-year follow-up on over 23,000 patients and a
      large observational database with long-term follow-up on over 4000 patients.

PMID- 18613252
TI  - Analysis of cross-over designs with serial correlation within periods using semi
      parametric mixed models.
AB  - The use of semi-parametric mixed models has proven useful in a wide variety of
      settings. Here, we focus on the application of the methodology in the particular
      case of a cross-over design with relatively long sequences of repeated
      measurements within each treatment period and for each subject. Other than an
      overall measure of the difference between each one of the experimental groups and
      the control group, specific time point comparisons may also be of interest. To
      that effect, we propose the use of flexible semi-parametric mixed models,
      enabling the construction of simulation-based simultaneous confidence bands. The
      bands take into account both between- and within-subject variabilities, while
      simultaneously correcting for multiple time point comparisons. Owing to the
      relatively long sequences of measurements per subject, the presence of serially
      correlated errors is anticipated and investigated. We illustrate how several
      formulations of semi-parametric mixed models can be fitted and the construction
      of simulation-based simultaneous confidence bands using SAS PROC MIXED.

PMID- 18613253
TI  - Eating disorders and disordered eating in Israel: an updated review.
AB  - Israel presents a unique opportunity to study the role of socio-cultural
      parameters in the development of mental disturbances because of the exceptional
      diversity of the Israeli society. In the present review, we aimed to analyse the
      current state of disordered eating in Israel by means of an extensive literature
      review. The following are the main findings of our review: The frequency of
      maladaptive eating among female and male Israeli Jewish adolescents is higher in
      comparison to many other Westernized countries. Among different Jewish sub
      populations, Kibbutz women have been found until recently to show higher rates of
      disordered eating in comparison to other Israeli samples. Recent studies show no
      such difference between Kibbutz members and the general Israeli population. No
      clear-cut findings emerge with respect to the influence of immigration and degree
      of Jewish religious affiliation on the occurrence of disordered eating. In
      contrast, disordered eating is less prevalent in Israeli-Arabs compared with
      Israeli-Jews. Moreover, diverse Israeli-Arab groups show different rates of
      disordered eating. We discuss the high rate of disordered eating in Israeli youth
      in light of Israel being a culture in transition that is constantly exposed to
      the risk of terrorism. The changes in the rates of disordered eating in the
      Kibbutzim are discussed in light of the dramatic societal changes occurring in
      these communities within a relatively brief period of time. The low rates of
      disordered eating in Israeli-Arabs reflect the traditional non-Westernized
      characteristics of their society, whereas the differences between diverse Arab
      sub-populations depend upon the degree of exposure to Westernized influences and
      the presence of conflicts between modern and traditional values.

PMID- 18613254
TI  - Identification and characterisation of childhood cerebellar tumours by in vivo
      proton MRS.
AB  - (1)H MRS has great potential for the clinical investigation of childhood brain
      tumours, but the low incidence in, and difficulties of performing trials on,
      children have hampered progress in this area. Most studies have used a long-TE,
      thus limiting the metabolite information obtained, and multivariate analysis has
      been largely unexplored. Thirty-five children with untreated cerebellar tumours
      (18 medulloblastomas, 12 pilocytic astrocytomas and five ependymomas) were
      investigated using a single-voxel short-TE PRESS sequence on a 1.5 T scanner.
      Spectra were analysed using LCModel to yield metabolite profiles, and key
      metabolite assignments were verified by comparison with high-resolution magic
      angle-spinning NMR of representative tumour biopsy samples. In addition to
      univariate metabolite comparisons, the use of multivariate classifiers was
      investigated. Principal component analysis was used for dimension reduction, and
      linear discriminant analysis was used for variable selection and classification.
      A bootstrap cross-validation method suitable for estimating the true performance
      of classifiers in small datasets was used. The discriminant function coefficients
      were stable and showed that medulloblastomas were characterised by high taurine,
      phosphocholine and glutamate and low glutamine, astrocytomas were distinguished
      by low creatine and high N-acetylaspartate, and ependymomas were differentiated
      by high myo-inositol and glycerophosphocholine. The same metabolite features were
      seen in NMR spectra of ex vivo samples. Successful classification was achieved
      for glial-cell (astrocytoma + ependymoma) versus non-glial-cell (medulloblastoma)
      tumours, with a bootstrap 0.632 + error, e(B.632+), of 5.3%. For astrocytoma vs
      medulloblastoma and astrocytoma vs medulloblastoma vs ependymoma classification,
      the e(B.632+) was 6.9% and 7.1%, respectively. The study showed that (1)H MRS
      detects key differences in the metabolite profiles for the main types of
      childhood cerebellar tumours and that discriminant analysis of metabolite
      profiles is a promising tool for classification. The findings warrant
      confirmation by larger multi-centre studies.

PMID- 18613255
TI  - Mitigation of radiation-induced skin injury by AAV2-mediated MnSOD gene therapy.
AB  - BACKGROUND: Radiation-induced, long-lived free radicals, reactive oxygen species
      and pro-inflammatory cytokines have been implicated in the resultant tissue
      injury after exposure to ionizing radiation. METHODS: An approach designed to
      reduce the damaging effects of reactive oxidants employs metalloenzymes of
      superoxide dismutase (SOD), such as MnSOD. Recombinant adeno-associated virus 2
      (AAV2) provides safe and long-term expression in humans. We tested the
      effectiveness of AAV2-MnSOD-hrGFP, a vector expressing MnSOD and green
      fluorescent protein (GFP) in preclinical models. RESULTS: Infection of cultured
      cells with AAV2-MnSOD-hrGFP showed enhanced expression of MnSOD and GFP.
      Sustained expression of GFP was achieved for at least 1 month in vivo following
      administration of AAV2-MnSOD-hrGFP to subcutaneous tissue of C57BL/6J mice. A
      single subcutaneous injection of AAV2-MnSOD-hrGFP significantly mitigated acute
      skin injury following single dose of irradiation of either 30 or 35 Gy.
      CONCLUSIONS: The proof-of-concept demonstrated in the present study together with
      the known safety profile in humans indicate that AAV-mediated MnSOD expression
      has potential countermeasure utility against normal tissue injury following
      radiation therapy or radiological accident.

PMID- 18613256
TI  - Influence of relative configuration of disubstituted cyclopentanes and -hexanes
      on 13C shifts.
AB  - (13)C shifts of disubstituted cyclopentane and cyclohexane derivatives were
      compared in dependence on the relative configuration of the two substituents. A
      diequatorial substitution correlates with deshielding compared to other
      substitution patterns. Some novel fluorinated cyclopentanes and -hexanes
      including their DFT calculation-assisted structure elucidation are described.

PMID- 18613257
TI  - Dominant marker vectors for selecting yeast mating products.
AB  - We have developed plasmid vectors to enable selection of diploids from mating
      reactions between haploid strains that lack compatible recessive genetic markers.
      The plasmids bear one of five different dominant selectable markers, kanMX4,
      hphMX4, natMX4, patMX3 or ZEO, a yeast origin of replication, and the URA3 gene.
      Diploids can be selected from mating reactions between haploids transformed with
      plasmids expressing different dominant markers, by using a combination of drugs
      that select for both markers. Following non-selective growth, diploids that
      subsequently become cured of the plasmids can be directly selected on 5-FOA, for
      ura3 auxotrophs, or identified by replica-plating onto appropriate selective
      media.

PMID- 18613258
TI  - Complete basis set B3LYP NMR calculations of CDCl3 solvent's water fine spectral
      details.
AB  - The assignment of singlet at 1.55 ppm and the 1:1:1 triplet at 1.519 ppm to H(2)O
      and HOD in the 400 MHz (1)H NMR spectrum of CDCl(3) solvent were supported by
      complete basis set (CBS) GIAO-B3LYP calculated chemical shift and the CBS B3LYP
      estimated (2)J(D,H) spin-spin coupling constant (SSCC). The CBS fitting of
      B3LYP/cc-pCVxZ and B3LYP/pcJ-n predicted SSCC values, the accurate value of
      (2)J(D,H) = -1.082 +/- 0.030 Hz of HOD in chloroform-d(1) and the H/D isotopic
      shift of 0.0307(1) ppm were reported for the first time. The agreement between
      CBS B3LYP predicted chemical shift, spin-spin values and experiment was good.

PMID- 18613259
TI  - Targeted identification of phosphorylated peptides by off-line HPLC-MALDI-MS/MS
      using LC retention time prediction.
AB  - Protein phosphorylation is a type of posttranslational modification which plays
      an important role in cell regulation and signal transduction. Because of its
      biological relevance, a considerable amount of interest has been paid to the
      development of efficient techniques for phosphopeptide analysis. Although
      advances in MS control have enabled the high-throughput discovery of proteins
      from limited amounts of sample, automated selection of MS/MS precursor ions based
      on intensity alone can significantly hamper the detection of low-abundance
      phosphopeptides. On the basis of the observation that the introduction of a
      phosphate moiety does not dramatically change peptide retention time in reverse
      phase chromatography, phosphopeptide specific MS/MS fragmentation attempts based
      on LC retention time and m/z were evaluated using a standard protein mixture,
      then using in vitro phosphorylated myelin basic protein. Results indicated that
      the majority (98%) of phosphopeptides identified eluted within a +/- 4-min window
      of the predicted LC elution time. While studies presented here are primarily
      proof of concept in nature, data suggest that the use of LC retention time
      prediction could be a valuable constraint for the identification of
      phosphopeptides within a set of off-line LC deposited sample spots. It is
      expected that the development of these methods will not only permit the targeted
      identification of protein phosphorylation sites but also allow the in-depth
      analysis of the dynamic events linked to the posttranslational modification.

PMID- 18613260
TI  - The state of dietary supplement adverse event reporting in the United States.
AB  - PURPOSE: The Dietary Supplements Information Expert Committee (DSI-EC; the
      Committee) of the United States Pharmacopeial Convention (USP) reviews safety
      profiles of dietary supplements before development of USP-National Formulary (USP
      NF) quality monographs. Because the veracity of dietary supplement adverse event
      reports (DS AERs) directly affects DSI-EC safety reviews, the Committee reviewed
      the current status of DS AER reporting in the US. METHODS: DSI-EC reviewed PubMed
      searches, information from the US Food and Drug Administration's (FDA) MedWatch
      program, the Toxic Exposure Surveillance System (TESS) of the American
      Association of Poison Control Centers (AAPCC), and reports from US and other
      agencies. DSI-EC analyzed this information to identify key factors that affect
      the quality of DS AERs. RESULTS: The overall incidence of DS AERs appears
      generally to be low. However, the primary reporting portal (FDA MedWatch)
      receives fewer AERs than do poison control centers (PCCs), and limited
      coordination exists among national and international surveillance programs for
      evaluating signals that may indicate potential public health risks. Both
      inadequate and poor-quality reporting of DS AERs are major limitations of DS
      safety monitoring in the US. CONCLUSIONS: Based on its assessments, the Committee
      advances recommendations to improve the quality of reporting, monitoring, and
      assessing DS AERs. These include (1) enhanced data collection approaches, (2)
      improved coordination of AER surveillance programs, (3) strengthening of
      educational programs for public and health care sectors, and (4) conduct of
      research concerning the safety of DS. If taken, these approaches are expected to
      improve the health and well-being of DS users.

PMID- 18613261
TI  - Diagnostic codes for sudden cardiac death and ventricular arrhythmia functioned
      poorly to identify outpatient events in EPIC's General Practice Research
      Database.
AB  - PURPOSE: To examine the validity of OXMIS/Read diagnoses of hospitalization for
      sudden cardiac death and ventricular arrhythmia (SD/VA) for use in studies of
      arrhythmogenic effects of outpatient medications in the General Practice Research
      Database (GPRD). METHODS: We identified putative occurrences of hospitalization
      for SD/VA in patients receiving outpatient prescriptions for cisapride,
      domperidone, or metoclopramide. We then administered a questionnaire to general
      practitioners (GPs) caring for these patients, requested hospital discharge
      consult letters, and examined the positive predictive value (PPV) of diagnostic
      codes in identifying outpatient events precipitating hospitalization. RESULTS: We
      identified 84 putative events, 38 (45%) of which occurred in patients cared for
      by GPs participating in the follow-up scheme. Thirty of 38 questionnaires (79%)
      were completed. The PPV for the occurrence of any SD/VA was 93% (95% CI, 78-99%).
      However, the PPV for SD/VA occurrence in an outpatient setting precipitating a
      hospitalization was only 23% (95% CI, 10-42%). The majority of inpatient
      diagnostic codes reflected events occurring after hospital admission, not
      precipitating it. CONCLUSIONS: While computerized codes for SD/VA agreed well
      with physician diagnosis, they operated poorly to identify events occurring in an
      outpatient setting. Studies of SD/VA in the GPRD should verify events on a case
      by-case basis.

PMID- 18613262
TI  - Using tensor product splines in modeling exposure-time-response relationships:
      application to the Colorado Plateau Uranium Miners cohort.
AB  - An adequate depiction of exposure-time-response relationships is important in
      assessing public health implications of an occupational or environmental
      exposure. Recent advances have focused on flexible modeling of the overall shape
      of latency. Methods are needed to allow for varying shapes of latency under
      different exposure profiles. A tensor product spline model is proposed for
      describing exposure-response relationships for protracted time-dependent
      occupational exposure histories in epidemiologic studies. The methods use
      flexible multi-dimensional techniques to jointly model age, latency and exposure
      response effects. In analyzing data from the Colorado Plateau Uranium Miners
      cohort, a model that allows for varying exposure-dependent latency shapes is
      found to be superior to models that only allowed for an overall latency curve.
      Specifically, the model suggests that, at low exposure levels risk increased at
      short latencies followed by a slow decline for longer latency periods. On the
      other hand, risk was higher but did not change much by latency for higher
      exposure levels. The proposed methodology has the advantage of allowing for
      latency functions that vary by exposure levels and, conversely, exposure-response
      relationships that are influenced by the latency structure.

PMID- 18613263
TI  - Inverse probability weighted estimation of the marginal odds ratio:
      correspondence regarding 'The performance of different propensity score methods
      for estimating marginal odds ratios'.

PMID- 18613264
TI  - Handwriting speed: duration of testing period and relation to socio-economic
      disadvantage and handedness.
AB  - In the course of norm-referencing the Handwriting Speed Test (HST) for 8- to 18
      year-olds in the Irish education system, the authors examined the issue of the
      duration of the handwriting test period, the relation of handwriting speed to
      socio-economic disadvantage and the comparative handwriting speed of left- and
      right-handed students. The literature reports some concerns about the
      generalizability of results from a short-duration handwriting speed test, some
      evidence that children from poorer backgrounds are less proficient at
      handwriting, and conflicting results on the relation of handedness to speed of
      handwriting. The results of this study suggest that the addition of a further 9
      minute test to the 3-minute test of the HST would improve its ability to predict
      handwriting speed problems in everyday extended writing tasks, such as
      examinations, and would also identify some children who are wrongly classified as
      slow writers on the 3-minute test. The results also indicate a markedly lower
      than-average handwriting speed for children attending designated disadvantaged
      schools. The results suggest that neither left- nor right-handed children have a
      consistent advantage in handwriting speed.

PMID- 18613265
TI  - Quantitative manganese tract tracing: dose-dependent and activity-independent
      terminal labelling in the mouse visual system.
AB  - At concentrations sufficient for visualisation using MRI, manganese (Mn) is
      believed to behave as a calcium analogue. This study examines different
      concentrations of Mn for enhanced MR tract tracing. The premise of activity
      dependent axonal transport was also examined by partial or complete blockade of
      retinal ganglion cell activity. Quantitative T(1) maps and semi-quantitative
      normalised signal intensities in the superior colliculi facilitated assessment of
      applied intraocular concentrations and activity dependence, respectively. Varying
      the concentration of applied Mn revealed a non-monotonic profile, with optimal,
      unfavourable and undesirable effects noted: 25 mM proved optimal, showing a
      maximal decrease in T(1), whereas 400 mM was associated with no terminal-field
      enhancement. The estimated vitreal concentration for optimal transport of Mn (2
      mM) is substantially lower than that used in previous studies of the mouse. Both
      the partial blockade of inputs to 50% of retinal ganglion cells by a mGluR6
      glutamate agonist and the complete blockade of all retinal ganglion cell activity
      with tetrodotoxin failed to decrease the relative enhancement in the superior
      colliculus. The failure to prevent axonal transport of Mn by blocking activity
      (and therefore theoretically the intracellular influx) appeared to be
      paradoxical. The optimal vitreal concentration of Mn has previously been shown to
      facilitate massive intracellular uptake of Mn, competitively blocking calcium,
      and 1 mM Mn blocks neurotransmission pre-synaptically. These results suggest
      that, at concentrations required for optimal Mn-enhanced MRI tract tracing in the
      visual system of the mouse, the uptake and transport of Mn may be dominated by
      passive mechanisms, which may also block neurotransmission.

PMID- 18613266
TI  - Restricted transgene persistence after lentiviral vector-mediated fetal gene
      transfer in the pregnant rabbit model.
AB  - BACKGROUND: Prenatal gene transfer may enable early causal intervention for the
      treatment or prevention of many devastating diseases. Nevertheless, permanent
      correction of most inherited disorders requires a sustained level of expression
      from the therapeutic transgene, which could theoretically be achieved with
      integrating vectors. METHODS: Rabbit fetuses received 8.5 x 10(6) HIV-based
      recombinant lentivirus particles containing the enhanced green fluorescent
      protein (EGFP) transgene by intrahepatic, intra-amniotic or intraperitoneal
      injection at 22 days of gestation. Provirus presence and transgene expression in
      rabbit tissues were evaluated at both 1.5 and 16 weeks post-in utero intervention
      by polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively.
      Moreover, we assessed persistence of EGFP by immunohistochemistry. Enzyme-linked
      immunosorbent assays confirmed the development of antibodies specific against
      both the viral vector and the reporter protein. RESULTS: Regardless of the route
      of administration employed, lentiviral vector-based in utero gene transfer was
      safe and reached 85% of the intervened fetuses at birth. However, the integrated
      provirus frequency was significantly reduced to 50% of that in young rabbits at
      16 weeks post-treatment. In these animals, EGFP expression was evident in many
      tissues, including cytokeratin 5-rich basal cells from stratified and
      pseudostratified epithelia, suggesting that the lentiviral vector might have
      reached progenitor cells. Conversely, we identified the presence of immune
      inflammatory infiltrates in several EGFP-expressing tissues. Moreover, almost 70%
      of the lentiviral vector-treated rabbits elicited a humoral immune response
      against the viral envelope and/or the EGFP. CONCLUSIONS: At two-thirds
      gestational age, the adaptive immune system of the rabbit appears a relevant
      factor limiting transgene persistence and expression following lentiviral vector
      mediated in utero gene transfer.

PMID- 18613268
TI  - Major depression and emergency medical services utilization in community-dwelling
      elderly persons with disabilities.
AB  - OBJECTIVE: To examine the association between major depression and emergency
      medical services (EMS) use by community-dwelling older adults with disabilities.
      METHODS: A prospective observational.study including 1,444 participants age 65+
      in 19 counties in three US states that participated in the Medicare Primary and
      Consumer-Directed Care Demonstration. Eligibility criteria included needing or
      receiving help with either 2+ activities of daily living (ADLs) or 3+
      instrumental ADLs, and having received recent significant healthcare services
      use. The presence of major depression was measured at baseline by the MINI Major
      Depressive Episode module. EMS utilization data for the following 2 years were
      obtained from a daily journal concurrently completed by each subject or a
      caregiver. RESULTS: More persons with major depression (43%) than without (35%)
      reported EMS use. When other factors were controlled in a logistic regression
      model, this effect was no longer statistically significant. However, of those
      with at least one episode of EMS transport, the depressed reported significantly
      (25%) more episodes (mean = 2.10) than the non-depressed (mean = 1.68). Major
      depression was significantly associated with more EMS episodes in both Poisson (Z
      = 1.99; p = 0.047) and ordinary least squares (t = 2.08; p = 0.038) regression
      models. CONCLUSIONS: Depressed disabled older adults who utilize EMS have more
      EMS episodes than those without depression. This higher use may be driven in part
      by affective illness. Research is needed to determine whether more EMS episodes
      are necessary to address symptoms of major depression, especially suicidal
      ideation, or whether they are due to other illnesses that are exacerbated by
      symptoms of major depression.

PMID- 18613270
TI  - Differences between collisionally activated and electron-transfer dissociations
      found for CH(2)X(2)(X = Cl, Br, and I) by using alkali-metal targets.
AB  - High-energy collisionally activated dissociation (HE-CAD) and high-energy
      electron- transfer dissociation (HE-ETD) on collisions with alkali-metal targets
      (Cs, K, and Na) were investigated for CH(2)X(2) (+) (X = Cl, Br, and I) ions by
      tandem mass spectrometry (MS/MS). In the HE-CAD spectra observed, peaks
      associated with CH(2)X(+) ions formed by a loss of a halogen atom are always
      predominant regardless of precursor ions and target metals. The observation of
      the predominant CH(2)X(+) ions is explained by the lowest energy levels of the
      fragments of CH(2)X(+) + X among the possible fragment energy levels and internal
      energy distribution in HE-CAD. In the charge-inversion spectra, relative peak
      intensities of the negative ions formed by HE-ETD strongly depend on the
      precursor ions and the target metals. While the CHCl(2) (-) ion was predominant
      in the spectra of CH(2)Cl(2) (+) regardless of target species, the most intense
      peaks in those of CH(2)Br(2) (+) and CH(2)I(2) (+) were ascribed to either Br(-)
      or CH(2)Br(-) and either I(-) or I(2) (-), respectively, depending on the target
      metals. The dependence of the relative intensities of the fragment ions by HE-ETD
      on the precursor ions and target species are discussed on the basis of the energy
      levels of the neutral fragments and the narrow internal-energy distribution
      resulting from the near-resonant neutralization. It was demonstrated that HE-ETD
      using the alkali-metal targets provided rich information on the dissociation of
      the neutral species.

PMID- 18613269
TI  - Stressful life events in older bipolar patients.
AB  - OBJECTIVE: Theories about the impact of stressful life events (SLE) in bipolar
      disorder have focused on their role early in the disease. Few studies have
      examined SLE in older bipolar patients. We wanted to assess the impact of SLE in
      late life bipolar disorder METHODS: We evaluated negative SLE experienced by
      older bipolar subjects compared with younger bipolar subjects and older controls
      for number, type, and their association with phase of illness, age of onset, and
      previous episodes. RESULTS: Both younger and older bipolar subjects have more SLE
      than similarly aged controls. There was no significant difference in the number
      of stressors that younger and older bipolar subjects experienced, based on mood
      state, previous episodes, or age-of-onset. Both older and younger depressed
      bipolar subjects reported more SLE in the previous 12 months compared with those
      in a manic state. CONCLUSIONS: Negative SLE are much more prevalent in bipolar
      patients compared with age-matched controls, and continue to be frequent in later
      life.

PMID- 18613267
TI  - Bringing the bedside to the bench, and then to the community: a prospectus for
      intervention research in late-life anxiety disorders.
AB  - BACKGROUND: Anxiety disorders are highly prevalent in elderly persons, and they
      are associated with functional impairment, poorer quality of life, and adverse
      long-term consequences such as cognitive decline. Intervention research in late
      life anxiety disorders (LLAD) lags behind where it ought to be. Research in
      cognitive neuroscience, aging, and stress intersects in LLAD and provides the
      opportunity to develop innovative interventions to prevent chronic anxiety and
      its consequences in this age group. METHODS: This paper evaluates gaps in the
      evidence base for treatment of LLAD and synthesizes recent research in cognitive
      neuroscience, basic behavioral science, stress, and aging. RESULTS: We examine
      three intervention issues in LLAD: (1) prevention; (2) acute treatment; and (3)
      pre-empting adverse consequences. We propose combining randomized controlled
      trials (RCTs) with mechanistic biobehavioral methodologies as an optimal approach
      for developing novel, optimized, and personalized treatments. Additionally, we
      examine three barriers in the field of LLAD research: (1) How do we measure
      anxiety?; (2) How do we raise awareness?; (3) How will we ensure our research is
      applicable to underserved populations (particularly minority groups)?
      CONCLUSIONS: This prospectus outlines approaches for intervention research that
      can reduce the morbidity of LLAD.

PMID- 18613271
TI  - Estimation method of the semiparametric mixture cure gamma frailty model.
AB  - Mixture cure frailty model has been proposed to analyze censored survival data
      with a cured fraction and unobservable information among the uncured patients.
      Different from a usual mixture cure model, the frailty model is employed to model
      the latency component in the mixture cure frailty model. In this paper, we extend
      the mixture cure frailty model by incorporating covariates into both the cure
      rate and the latency distribution parts of the model and propose a semiparametric
      estimation method for the model. The Expectation Maximization (EM) algorithm and
      the multiple imputation method are employed to estimate parameters of interest.
      In the simulation study, we show that both estimation methods work well. To
      illustrate, we apply the model and the proposed methods to a data set of failure
      times from bone marrow transplant patients.

PMID- 18613272
TI  - Semi-parametric maximum likelihood estimates for ROC curves of continuous-scale
      tests.
AB  - In this paper, we propose a new semi-parametric maximum likelihood (ML) estimate
      of a receiver operating characteristic (ROC) curve that satisfies the property of
      invariance of the ROC curve and is easy to compute. We show that our new
      estimator is sqrt[n]-consistent and has an asymptotically normal distribution.
      Our extensive simulation studies show that the proposed method is efficient and
      robust. Finally, we illustrate the application of the proposed estimator in a
      real data set.

PMID- 18613273
TI  - 'Smooth' inference for survival functions with arbitrarily censored data.
AB  - We propose a procedure for estimating the survival function of a time-to-event
      random variable under arbitrary patterns of censoring. The method is predicated
      on the mild assumption that the distribution of the random variable, and hence
      the survival function, has a density that lies in a class of 'smooth' densities
      whose elements can be represented by an infinite Hermite series. Truncation of
      the series yields a 'parametric' expression that can well approximate any
      plausible survival density, and hence survival function, provided the degree of
      truncation is suitably chosen. The representation admits a convenient expression
      for the likelihood for the 'parameters' in the approximation under arbitrary
      censoring/truncation that is straightforward to compute and maximize. A test
      statistic for comparing two survival functions, which is based on an integrated
      weighted difference of estimates of each under this representation, is proposed.
      Via simulation studies and application to a number of data sets, we demonstrate
      that the approach yields reliable inferences and can result in gains in
      efficiency over traditional nonparametric methods.

PMID- 18613274
TI  - Robotic appendectomy in gynaecological surgery: technique and pathological
      findings.
AB  - BACKGROUND: We evaluated the feasibility, safety and pathological findings of
      incidental robotic appendectomy in patients undergoing robotic gynaecological
      surgery. METHODS: Retrospective analysis of 107 consecutive cases of robotic
      appendectomy done in conjunction with other robotic gynaecological procedures
      between May 2004 and January 2007. RESULTS: All appendectomies were performed
      robotically in conjunction with other robotic procedures. Mean time for
      appendectomy was 3.4 min. No perioperative complications related to appendectomy
      were encountered. Among 90 patients with no gynaecological malignancy, 57
      patients reported chronic pelvic pain preoperatively and 21 (37%) of them had an
      abnormal appendiceal pathology as compared to only 5 (15%) of the 33 patients
      with no pelvic pain (OR. 3.2; 95% CI, 1.1-9.7, p = 0.032). Of seven patients with
      ovarian malignancy, three (42%) had appendicular metastasis. CONCLUSION:
      Incidental robotic appendectomy can be performed safely without the need for
      switching to conventional laparoscopy. It should be considered in patients
      undergoing robotic pelvic surgery for pelvic pain and ovarian malignancy.

PMID- 18613276
TI  - Erratum: Screening statins for possible carcinogenic risk: up to 9 years of
      follow-up of 361 859 recipients.

PMID- 18613275
TI  - Improved retroviral vector design results in sustained expression after adult
      gene therapy in mucopolysaccharidosis I mice.
AB  - BACKGROUND: Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease due to
      alpha-L-iduronidase (IDUA) deficiency that results in the accumulation of
      glycosaminoglycans (GAG). Gene therapy can reduce most clinical manifestations,
      but mice that receive transfer as adults lose expression unless they receive
      immunosuppression. Increasing liver specificity of transgene expression has
      reduced immune responses to other genes. METHODS: A gamma retroviral vector was
      generated with a liver-specific human alpha1-antitrypsin promoter and the canine
      IDUA cDNA inverted relative to the retroviral long-terminal repeat. Adult MPS I
      mice received the vector intravenously at 6 weeks of age and were assessed for
      expression via serial serum IDUA assays. Functional testing and organ analysis
      were performed at 8 months. RESULTS: This vector resulted in high specificity of
      expression in liver, and serum IDUA activity was stable in 90% of animals.
      Although the average serum IDUA activity was relatively low at 12.6 +/- 8.1
      units/ml in mice with stable expression, a relatively high percentage of enzyme
      contained the mannose 6-phosphorylation necessary for uptake by other cells. At
      6.5 months after transduction, most organs had high IDUA activity and normalized
      GAG levels. There was complete correction of hearing and vision abnormalities and
      significant improvements in bone, although the aorta was refractory to treatment.
      CONCLUSIONS: Stable expression of IDUA in adult MPS I mice can be achieved
      without immunosuppression by modifying the vector to reduce expression in the
      spleen. This approach may be effective in patients with MPS I or other lysosomal
      storage diseases.

PMID- 18613277
TI  - The McLafferty rearrangement in the Glu residue in a cyclic lipopeptide
      determined by Q-TOF MS/MS.
AB  - The intraresidue rearrangement and loss of the side chain of the Glu residue was
      found through MS/MS analysis of both original and methanol-esterified
      lipopeptides. Both Glu and Asp residues in the cyclic lipopeptide were
      esterified. The MS/MS results showed that the loss of fragment 72 or 86 was
      induced by McLafferty-type rearrangement from the Glu or esterified Glu. The
      mechanism of loss of the Glu residue can be used to determine or to corroborate
      the existence of the Glu and to help understand the fragment formation in MS/MS.
      The cleavage mechanism and m/z intensities imply that the sodium ion was easier
      attached and the cleavage would easily occur at specific sites.

PMID- 18613279
TI  - Resonance excitation and dynamic collision-induced dissociation in quadrupole ion
      traps using higher-order excitation frequencies.
AB  - Fragmentation of the pentapeptide leucine enkephalin (YGGFL) is accomplished via
      higher-order resonances combined with simultaneous analysis of low-mass product
      ions. Two methods of achieving excitation are explored: (1) 0.5 ms resonant
      excitation at the omega and at Omega-omega secular frequencies of ion motion
      (where Omega is the radio-frequency (rf) drive frequency) in a manner similar to
      both pulsed q collision-induced dissociation (PQD) and high amplitude short time
      excitation (HASTE), and (2) 0.5 ms pulse of the omega or at Omega-omega
      excitation frequencies when the secular frequency of the ions is quickly swept
      across resonance conditions (pulsed q dynamic CID, PqDCID). In both methods of
      excitation, the rf amplitude on the ring electrode is rapidly decreased after
      excitation, therefore enabling analysis of low-mass product ions. Maximum
      fragmentation efficiencies of approximately 20% can be obtained with pulsed CID
      with both regular and high-order frequency excitation, while pulsed DCID offers
      maximum efficiencies of approximately 12%. All the excitation methods studied
      offer increased internal energy depositions when compared to conventional CID, as
      measured by the a4/b4 product ion ratios of leucine enkephalin. These ratios were
      as high as 13:1 for pulsed CID and 8:1 for PqDCID. Successful mass analysis of
      the low-mass ions is observed with both pulsed CID and PqDCID. The combined
      benefit of high internal energy deposition and wider dynamic mass range offers
      the possibility of increased sequence coverage and the identification of unique
      internal fragments or high-energy product ions which may provide complementary
      information to biological applications of conventional CID. This is the first
      report on deliberate fragmentation of precursor ions at a higher-order component
      of the ion secular frequency combined with a successful mass analysis of the low
      mass ions through pulsed CID and PqDCID.

PMID- 18613278
TI  - A retrospective evaluation of congestive heart failure and myocardial ischemia
      events in 14,237 patients with type 2 diabetes mellitus enrolled in 42 short
      term, double-blind, randomized clinical studies with rosiglitazone.
AB  - PURPOSE: Retrospectively investigate potential associations between rosiglitazone
      and congestive heart failure (CHF) and, separately, events of myocardial
      ischemia. METHODS: Data from 14 237 individuals in 42 short-term, double-blind,
      randomized studies of rosiglitazone versus placebo or active diabetes medications
      were analyzed across seven treatment comparisons using an exact logistic
      regression model, adjusted for number of major cardiovascular risk factors and
      duration of exposure. RESULTS: CHF incidence ranged 0-1.27% (SAEs) and 0.12-2.42%
      (all AEs) with rosiglitazone versus 0.07-0.75% (SAEs) and 0.25-1.36% (all AEs)
      with control. Higher odds ratios (95%CI) were observed for CHF SAEs with
      sulfonylurea- and insulin-containing combinations: rosiglitazone monotherapy
      versus placebo, 0.25 (<0.01-4.75); rosiglitazone monotherapy versus
      sulfonylurea/metformin monotherapy, 0.23 (<0.01-2.14); sulfonylurea +
      rosiglitazone versus sulfonylurea monotherapy, 0.95 (0.01-75.20); metformin +
      rosiglitazone versus metformin monotherapy, 0.60 (0.00-8.28); metformin +
      rosiglitazone versus metformin + sulfonylurea, 1.04 (0.39-2.86); sulfonylurea +
      metformin + rosiglitazone versus sulfonylurea + metformin, 3.15 (0.35-150.52);
      insulin + rosiglitazone versus insulin monotherapy, 1.63 (0.52-6.01). Myocardial
      ischemia incidence ranged 0.75-1.40% (SAEs) and 1.49-2.77% (all AEs) with
      rosiglitazone versus 0.21-2.04% (SAEs) and 0.56-2.38% (all AEs) with control.
      Each comparison had an OR >1, with wide confidence intervals generally including
      unity. With data pooling, more events of myocardial ischemia were observed with
      rosiglitazone (2.00%) versus control (1.53%) (HR 1.30, 95%CI 1.004-1.69).
      CONCLUSIONS: CHF incidence may be greater when rosiglitazone is combined with
      sulfonylureas or insulin. When data were pooled, more events of myocardial
      ischemia were observed with rosiglitazone versus control. Final results from
      RECORD will allow a more rigorous evaluation of the cardiovascular safety
      profile.

PMID- 18613280
TI  - Electrospray tandem mass spectrometry of alendronate analogues: fingerprints for
      characterization of new potential prodrugs.
AB  - 1-hydroxymethylene-1,1-bisphosphonic acids (HMBPs) are important drugs for the
      treatment of a variety of bone diseases. Since these compounds have no
      chromophore, their detection is challenging and mass spectrometry (MS) appears to
      be an appropriate sensitive tool. Our work deals with the analysis by
      electrospray ionization tandem mass spectrometry (ESI-MSn) of the well-known
      nitrogen-containing HMBP alendronate and of three analogues, considered as
      potential prodrugs. These four molecules share a common structure with different
      protecting groups on the phosphonic acid and on the amine functions. We describe
      the dissociation mechanisms of nitrogen-containing HMBPs in positive ion mode and
      we compare, in negative ion mode, our results with literature data. In both
      modes, the dissociations are essentially losses of ROH, and of phosphorus
      containing species (HPO2, ROP(OH)2 and ROPO(OH)2), where R=H, C6H5, or CH3OC6H5.
      These fingerprints will be of great value for differentiating alendronate from
      its potential prodrugs in complex biological mixtures.

PMID- 18613282
TI  - Preferences of general practitioners and carers of Alzheimer patients regarding
      the use of neuroleptics for behavioural disorders in Alzheimer's disease.

PMID- 18613281
TI  - Regenerate: assessing the feasibility of a strength-training program to enhance
      the physical and mental health of chronic post stroke patients with depression.
AB  - OBJECTIVE: The Regenerate pilot study explored whether a 10-week, community-based
      progressive resistance training (PRT) program could reduce depressive symptoms in
      depressed chronic stroke survivors. METHODS: Participants were screened for
      depressive status using the PHQ-9 and confirmed by psychiatric assessment.
      Eligible people (n = 45) were randomised to PRT or a waiting-list comparison
      group. The PRT program included two high intensity sessions/week for 10 weeks at
      a community-based gymnasium. Depressive status, physical and mental health and
      quality of life were measured at baseline, 10 weeks and 6 months. Muscle strength
      was assessed using 1 repetition maximum (1-RM) for upper and lower limbs.
      RESULTS: The participants' median age was 69 years: 27 were male. The
      intervention group had lower depression scores than the comparison group at all
      time points. At 6-month follow-up, there was a trend for PRT participants to be
      more likely to be no longer depressed than the comparison group, but the
      difference was not significant after adjusting for baseline scores. There were
      modest improvements in health and wellbeing over time, but many scores were lower
      than reported in non-depressed people. Intervention participants demonstrated
      significant improvements in strength. Program adherence was good: on average 75%
      of the 10-week program was completed. CONCLUSIONS: The intervention appeared to
      be feasible within a community-based setting. To optimize stroke recovery and
      improve the quality of life of stroke survivors, health professionals should
      continue to focus on helping survivors' mental health recovery as well their
      physical rehabilitation.

PMID- 18613283
TI  - Harm reduction among at-risk elderly drinkers: a site-specific analysis from the
      multi-site Primary Care Research in Substance Abuse and Mental Health for Elderly
      (PRISM-E) study.
AB  - OBJECTIVES: To assess the efficacy of a harm-reduction based intervention to
      enhance access to treatment and clinical outcomes among elderly at-risk drinkers.
      DESIGN: A site-specific secondary data analysis of Primary Care Research in
      Substance Abuse and Mental Health for Elders study (PRISM-E). PARTICIPANTS:
      Thirty-four at-risk drinkers age 65 or older who were randomized into one of two
      treatment conditions: an integrated care condition which incorporated a harm
      reduction based approach to treatment and an enhanced referral condition.
      MEASURES: Access to subsequent services and clinical outcomes were examined 6
      months post index-interview date. Clinical outcomes included changes in the
      number of drinks in the week prior to assessment, changes in the number of binges
      in the past 3 months prior to assessment, and changes in scores on the Short
      Michigan Alcoholism Screening Test-Geriatric Version (SMAST-G). RESULTS: At-risk
      drinkers in the integrated care condition were more likely to access treatment
      than at-risk drinkers assigned to the enhanced referral condition (93% vs 35%;
      chi(2) = 11.38, df = 1, p = 0.001). Among those who received treatment, there
      were no differences in the total amount of treatment visits or in the number of
      brief alcohol interventions received among at-risk drinkers in the two
      conditions. However, those in integrated care condition received services sooner
      than those in the referral condition. Those in the integrated care condition
      showed a significant decrease in the number of drinks in the past week and in the
      number of binge drinking episodes in the past 3 months while there were no
      significant changes in these outcomes among the at-risk drinkers in the enhanced
      referral condition. CONCLUSIONS: At-risk drinkers in the integrated care
      condition were more likely to access treatment and decrease harmful drinking
      behaviors than those in the enhanced referral condition. Implications for future
      research and treatment are discussed.

PMID- 18613284
TI  - A divergent approach to the preparation of cysteine and serine analogs.
AB  - Malonate diesters containing a prochiral quaternary carbon have been successfully
      transformed into analogs of cysteine and serine. The chiral half-esters are
      obtained in good yield, and enantioselectivity by selective hydrolysis using Pig
      Liver Esterase (PLE) as the catalyst. The resulting half-ester intermediates are
      transformed into alpha2, 2-, beta2, 2-, and beta3, 3-analogs of cysteine and
      serine. The methodology described here allows for the preparation of both
      enantiomers of the amino-acid analogs by selective manipulation of the ester and
      acid functionalities. This divergent strategy allows a common synthetic strategy
      to be used to prepare a variety of unnatural amino-acid classes from a common
      intermediate which should prove useful in the design of novel peptide libraries.

PMID- 18613285
TI  - Comments on 'active-control trials with binary data: a comparison of methods for
      testing superiority or non-inferiority using the odds ratio' by A. L. Siqueira,
      A. Whitehead and S. Todd, Statistics in Medicine 2008; 27:353-370.

PMID- 18613286
TI  - Isopeptide method: development of S-acyl isopeptide method for the synthesis of
      difficult sequence-containing peptides.
AB  - A novel strategy for a more efficient synthesis of difficult sequence-containing
      peptides, the S-acyl isopeptide method, was developed and successfully applied. A
      model pentapeptide Ac-Val-Val-Cys-Val-Val-NH2 was synthesized via its water
      soluble S-acyl isopeptide using an S-acyl isodipeptide unit, Boc-Cys(Fmoc-Val)
      OH. An S-acyl isopeptide possessing excellent water solubility could be readily
      and quantitatively converted to the native peptide via an S--N intramolecular
      acyl migration reaction at pH 7.4. Thus, the S-acyl isopeptide method provides a
      useful tool in peptide chemistry.

PMID- 18613287
TI  - Shifting sands: assessing the balance between public, private not-for-profit and
      private for-profit physical therapy delivery in Ontario, Canada.
AB  - BACKGROUND AND PURPOSE: The vast majority of health services within Canada's
      single payer universal health care system are publicly funded. Despite the highly
      political and controversial emphasis placed on public funding, the structure of
      delivery within this health care system does not require public ownership. In
      this research, we developed a conceptual framework for analysing the public and
      private mix of physical therapy (PT) delivery in the province of Ontario. We then
      applied this framework to examine the shifts in employment structure of physical
      therapists (PTs) in Ontario. METHODS: A two-phased health policy case study
      methodology was used. In the first phase, we reviewed publicly available
      documents and conducted a series of 30 key informant interviews in order to
      develop our framework. In the second phase, we applied the framework and
      performed secondary analysis of the provincial PT registration database to assess
      change in practice setting between 1996 and 2002. RESULTS: We identified nine
      models of delivery that fall into three categories of ownership structure: (a)
      public; (b) private not-for-profit; and (c) private for-profit. During the six
      year period between 1996 and 2002, the relative proportion of PTs employed in the
      not-for-profit sector decreased (from 59.6% to 54.8%) whereas the share in the
      for-profit sector grew (from 40.4% to 45.2%). CONCLUSIONS: The shifting balance
      in the structure of delivery may be transforming how PT services are provided in
      the province. Private for-profit providers appear to be increasing their market
      share; however, the outcomes relative to this shift has yet to be fully explored.
      Further policy and health services research is warranted to more fully understand
      the consequences of this shift on variables such as professional autonomy,
      access, cost and quality of services across Canada, but also within similar and
      dissimilar international jurisdictions.

PMID- 18613288
TI  - Effect of peptides bearing nuclear localization signals on therapeutic ultrasound
      mediated gene delivery.
AB  - BACKGROUND: One of the major limitations of nonviral gene delivery methods is
      nuclear transport of plasmid DNA (pDNA). Peptides bearing nuclear localization
      signal (NLS) were shown to mediate nuclear import of macromolecules. We have
      explored the use of cell-permeable peptides (CPP) bearing NLS sequences to
      enhance transfection mediated by a nonviral approach: therapeutic ultrasound
      (TUS). METHODS: Two CPP-NLS peptides which differ in the location of the NLS
      relative to the CPP were used: S4 13-PV and PV-S4 13. The peptides were attached
      to pDNA using electrostatic interactions. Gel-electrophoresis and fluorescent
      assays were performed to evaluate pDNA-peptide interactions and condensation
      effects. Confocal microscopy was used to evaluate pDNA-peptide interaction inside
      cells. Transfection studies were conducted with the luciferase gene, using pDNA
      peptides alone, or with the application of TUS. RESULTS: Attachment of both
      peptides to pDNA condensed the pDNA, with higher affinity for the S4(13)-PV
      peptide. This interaction protected pDNA from endonucleases, but was also
      reversible. Both peptides mediated pDNA delivery to cell cytoplasm, but less
      significantly to the nucleus. Thus, both peptides produced transfection in cells,
      when added after incubation with DNA, with higher transfection-level for PV-S4
      13. Application of TUS increased transfection mediated by these peptides, but was
      not higher compared to transfection using TUS and pDNA alone. CONCLUSIONS: This
      study suggests that CPP-NLS peptides may be used for condensing pDNA and bringing
      it into the cell cytoplasm, but their ability to mediate nuclear import of pDNA
      is insignificant.

PMID- 18613289
TI  - Understanding the causes of depression among prostate cancer patients:
      development of the Effects of Prostate Cancer on Lifestyle Questionnaire.
AB  - OBJECTIVE: Depression among prostate cancer patients remains a major source of
      distress for them and their families, has been linked with suicide, and has been
      shown to contribute to poorer longterm treatment outcomes. Most psychological
      assessment strategies focus upon the presence of depressive symptomatology
      without identifying the specific causal antecedents that lead to depression among
      this patient group, although this underlies effective individually-oriented
      treatment planning and delivery. METHOD: 150 prostate cancer patients completed
      self reports on anxiety, depression and lifestyle changes that they had
      experienced as a result of receiving a diagnosis of, and treatment for their
      cancer. The principal instrument being investigated was a measure of 50 lifestyle
      changes that had been developed from previous interviews with prostate cancer
      patients. RESULTS: Data indicated significant relationships between depression
      scores and the frequency of unpleasant lifestyle changes and the ratings that
      participants gave to these changes, supporting a model of depression as an
      adaptive withdrawal from noxious stimuli and environments. Psychometric data
      provided a method of deleting several items so that a clinical analysis and a
      research scale of 36 items was developed for use with prostate cancer patients.
      CONCLUSION: Implications for treatment are discussed in terms of accurate
      identification of antecedents that lead to a further understanding of depression
      as an 'adaptive' response of active withdrawal from noxious environments.

PMID- 18613290
TI  - Nanopatterned collagen tubes for vascular tissue engineering.
AB  - Nanopatterned (330 nm wide channels) type I collagen films were prepared by
      solvent casting on poly(dimethyl siloxane) (PDMS) templates. These films were
      rolled into tubular constructs and crosslinked. Tubular constructs were incubated
      under cell culture conditions for 28 days and examined by stereomicroscopy and
      scanning electron microscopy (SEM) for the integrity of the structure. The
      nanopatterned films were also seeded with human vascular smooth muscle cells
      (VSMCs) and examined after immunostaining with fluorescence microscopy and SEM to
      assess the cell phenotype and alignment on the nanopatterns on the films.

PMID- 18613291
TI  - Association of glucose transporter 1 polymorphisms with type 2 diabetes in the
      Tunisian population.
AB  - BACKGROUND: T2DM is a complex metabolic disease. Genetic studies on T2DM have
      been of little help so far because several genetic association studies have shown
      conflicting results. In this study, we report the findings of a case-control
      study on three SNPs in the GLUT1 gene. For this, we investigated the association
      of GLUT1 genotypes and haplotypes with T2DM. RESEARCH DESIGN AND METHODS: All 273
      T2DM subjects (cases) and 343 healthy subjects (controls) were genotyped using
      the polymerase chain reaction restriction fragment length polymorphism. RESULTS:
      Results showed that the GT genotype of XbaI SNP could increase the risk of
      susceptibility to T2DM to 2.4 and that TAT is a 'risk haplotype' conferring a
      risk of 3.4 to T2DM. CONCLUSION: The TAT haplotype of the GLUT1 gene confers
      susceptibility to T2DM in the Tunisian population.

PMID- 18613292
TI  - Genetic testing in familial melanoma: uptake and implications.
AB  - OBJECTIVE: We report on the uptake and psychological impact of p16-Leiden genetic
      testing to contribute to a greater understanding of counseling melanoma families.
      METHODS: Within a defined research setting, genetic counseling and testing were
      offered to members of p16-Leiden-positive melanoma pedigrees, at risk of carrying
      a gene defect associated with an increased risk of melanoma and pancreatic
      cancer. RESULTS: One hundred and eighty-four individuals sought counseling, of
      which 141 (77%) opted for genetic testing. Uptake of genetic counseling and
      testing, and psychological motivation was evaluated in 94 (57%) individuals.
      Higher pre-test risk of carrying the mutation and older age proved significantly
      predictive for counseling uptake. Age was predictive for test acceptance, whereas
      fearful test expectancies predicted test decline. Counselees had lower distress
      levels than those reported in other oncogenetic testing settings. CONCLUSION: We
      are the first to report on genetic testing for familial melanoma. Following the
      first counseling session, we found a relatively high uptake rate for p16-Leiden
      testing and no clinically worrisome levels of distress.

PMID- 18613293
TI  - Profiling of yew hair roots from various species using ultra-performance liquid
      chromatography/electrospray ionization mass spectrometry.
AB  - An efficient and sensitive profiling approach to complex yew samples was
      developed using ultra-performance liquid chromatography/electrospray ionization
      mass spectrometry (UPLC/ESI-MS). The UPLC-based method displayed short analytical
      time and improved peak capability, as well as high sensitivity. The appropriate
      in-source collision-induced dissociation (CID) energy was employed to produce
      informative characteristic ions which could be used for stereochemical and sub
      structural assignment of yew constituents. The method was successfully applied in
      the rapid screening of yew hair roots from various species, and 53 constituents
      including 47 taxoids were detected from partially purified root extract. Notably,
      C-7 hydroxytaxane stereoisomers could be identified based on their different
      fragment ions under the optimal profiling conditions. It was also observed that
      hair roots from different Taxus species exhibited nearly identical chemical
      distribution, indicating they had similar metabolic frameworks. Additionally,
      Taxus root resources also display benign medicinal perspective because they have
      relatively simple chemical profiles and possess high yields of valuable taxanes
      such as paclitaxel, cephalomannine, 10-deacetylpaclitaxel and 7-xylosyltaxanes.

PMID- 18613294
TI  - High-throughput approaches towards the definitive identification of
      pharmaceutical drug metabolites. 1. Evidence for an ortho effect on the
      fragmentation of 4-benzenesulfinyl-3-methylphenylamine using electrospray
      ionisation mass spectrometry.
AB  - A 50 m/z unit loss from protonated 4-benzenesulfinyl-3-methylphenylamine has been
      observed and investigated using electrospray ionisation quadrupole ion trap mass
      spectrometry (ESI-QIT-MS). It was hypothesised that the specific fragmentation
      was affected by the presence of an ortho methyl group in relation to the
      sulfoxide functionality, i.e. an ortho effect influences the preferred
      dissociation pathway. This was because the des-methyl homologue did not display a
      50 m/z unit loss. This fragmentation was shown to be a two-step process with
      sequential losses of a hydroxyl radical and a thiol radical. Molecular modelling
      calculations showed that the most favourable site of protonation for 4
      benzenesulfinyl-3-methylphenylamine was the sulfoxide oxygen, which would
      facilitate the loss of a hydroxyl radical. Subsequent deuterium-exchange
      experiments confirmed that the loss was a hydroxyl radical and afforded
      definitive assignment of the site of protonation. Furthermore, the involvement of
      a single exchangeable hydrogen atom in the overall 50 m/z unit loss was
      demonstrated. Thus, supportive evidence was provided for the involvement of the
      ortho methyl group in the second stage of the fragmentation, leading to the loss
      of the thiol radical. Accurate mass measurements, performed using electrospray
      ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR
      MS), verified the elemental formulae of the individual losses. The ion structure
      following the 50 m/z unit loss was proposed to be a protonated aminofluorene and
      was supported by comparing the product ion spectrum of commercially available
      protonated 2-aminofluorene with the MS4 data of protonated 4-benzenesulfinyl-3
      methylphenylamine. Fragmentation mechanisms are proposed. The relevance of the
      loss with regards to pharmaceutical drug metabolite identification is discussed.

PMID- 18613295
TI  - Depression, distress and positive mood in late-stage cancer: a longitudinal
      study.
AB  - OBJECTIVES: To determine whether new-onset clinical depression emerges over time,
      and whether positive and negative mood levels change among patients with terminal
      cancer. METHODS: In this two-site study, 58 cancer patients seen at least twice
      were interviewed monthly until death or study termination. Major measures
      included the Patient Health Questionnaire-9, Holland System of Beliefs Inventory,
      and Positive and Negative Affect Schedule. RESULTS: At study entry, 7% of
      patients had major depressive disorder; another 9% had depressive symptoms but no
      Axis I diagnosis. Twenty-two percent were taking antidepressants. During visits
      ranging from 2 to 21 per patient, 76% of patients never had a depression
      diagnosis, 3% were always depressed, and 14% became depressed for the first time,
      almost exclusively at their final visit before death. Scores on positive mood
      were equivalent to or higher than scores on negative mood and did not change over
      time. Cancer site, hospice, spiritual beliefs, income, and caregiver mood were
      unrelated to depression. Spiritual beliefs were, however, associated with
      positive mood, hope, and better quality of life. CONCLUSIONS: In this exploratory
      study, terminally ill patients approaching death experienced positive as well as
      negative mood although a significant minority met criteria for major depression
      at the last visit before death. The findings suggest that major depression is not
      an inevitable part of the dying process in patients with terminal cancer.
      Further, the appropriateness of classifying sadness, loss of interest and
      thoughts that one would be better off dead in the last days of life as
      psychopathology should be reconsidered.

PMID- 18613297
TI  - (E)-4-alkoxycarbonylalkylthiochalcones: differentiation of isomeric derivatives
      by electron ionization mass spectrometry.
AB  - The principal fragmentation pathways of the molecular ions of 18 new (E)-4
      alkoxycarbonylalkylthiochalcones have been investigated. It has been shown that
      the data derived from electron ionization mass spectra (the relative abundance of
      the fragment ions and values of coefficients micro) can be used to differentiate
      the isomers. The fragmentation rules deduced here could help in the
      characterization of other chalcones of these types.

PMID- 18613296
TI  - Psychosocial issues in genetic testing for familial adenomatous polyposis: a
      review of the literature.
AB  - OBJECTIVES: Familial adenomatous polyposis (FAP) is characterized by the
      development of multiple adenomas in the colon that can lead to colorectal cancer.
      Being a carrier for FAP is hypothesized to have a negative impact on psychosocial
      well-being. This paper reviews the current literature on the psychosocial aspects
      of FAP. METHODS: Four literature databases were used to identify all papers
      published between 1986 and 2007 about psychosocial and behavioral issues in FAP
      related to genetic testing. The following topics were reviewed: uptake and
      psychosocial impact of genetic testing, endoscopic screening behavior and
      psychosocial well-being in general. RESULTS: Seventeen papers were identified.
      Across studies, genetic test uptake varied between 62 and 97%. Two out of three
      studies showed clinical levels of anxiety and/or depression after genetic
      testing. A minority of individuals were not reassured by a negative test result,
      and intended to continue endoscopic surveillance. Well-being (e.g. quality of
      life, family functioning) was found to be lower in some studies, while comparable
      to the general population in other studies. The studies had several shortcomings,
      such as mixed patient population (e.g. colorectal and breast cancer) and small
      sample sizes, and provided no information on other potentially important issues,
      such as psychosexual development. CONCLUSIONS: Future studies should employ
      larger sample sizes and standardized measurements. Additionally, future studies
      should address the long-term consequences of genetic testing for FAP,
      psychosexual development and consequences of FAP for the family as a whole.

PMID- 18613298
TI  - Cross-country disparities in health-care expenditure: a factor decomposition.
AB  - This note investigates the sources of international differences in the levels of
      per capita health-care expenditure, using data on the OECD countries between 1975
      and 2003. To that end, we use Theil's second measure of inequality for
      decomposing cross-country disparities in per capita health-care expenditure into
      the contributions of various factors: health-care expenditure expressed as a
      share of GDP, labour productivity, employment rate, activity rate and the ratio
      of working-age population to total population. Our results show that cross
      country differences in the share of GDP devoted to health-care expenditure and
      labour productivity are the main determinants of the level of dispersion in per
      capita health-care expenditure. On the contrary, existing disparities in the
      remaining explanatory factors considered play a less relevant role in this
      context. In any event, the analysis performed reveals that the overall inequality
      in per capita health-care expenditure decreased throughout the study period. This
      was due to the process of international convergence observed in most of the
      factors used to break down the level of per capita health-care expenditure.

PMID- 18613299
TI  - The transition from breast cancer 'patient' to 'survivor'.
AB  - BACKGROUND: While much is now known about breast cancer survivors' long-term
      health, quality of life, and psychological state, relatively little is known
      about the period immediately following completion of treatment, when women
      transition out of the role of breast cancer 'patient' to life as 'survivor'.
      OBJECTIVE: To explore women's fears regarding risk of cancer recurrence, sense of
      loss of medical monitoring, and social support from health-care providers and
      other patients, and the strategies they use to cope with these issues. METHOD:
      Focus group interviews were conducted with women who had completed adjuvant
      chemotherapy or radiation for new stage I or II breast cancer in the prior 12
      months. Interviews were audio-taped, transcribed, and analyzed using a constant
      comparative analysis approach. RESULTS: Of 216 women identified as eligible, over
      half (155) were reached by telephone and invited to participate. Of those
      invited, 47 (30%) agreed. Findings suggest that while women acknowledge positive
      life changes as a result of the cancer experience, emotional and physical
      stresses are prevalent following the completion of treatment. CONCLUSION: The
      period of time when women who have been treated for breast cancer transition to
      life without treatment presents numerous emotional and physical challenges. By
      illuminating patients' experience during this transition period, this study
      provides insights into the development of interventions to support women after
      treatment.

PMID- 18613300
TI  - Risk perception and cancer worries in families at increased risk of familial
      breast/ovarian cancer.
AB  - While families at increased risk for familial breast/ovarian cancer continue to
      overestimate their cancer risk with increased cancer worries about the future,
      few studies have examined factors that affect inherited cancer risk perception
      and cancer worries in both survivors and unaffected female relatives. The purpose
      of this study was to examine variables that may affect cancer worries and risk
      perceptions from a family-based perspective in a racially diverse, community
      based, random sample of 146 dyads consisting of adult female breast and/or
      ovarian cancer survivors and their unaffected female relatives (N=292). Results
      indicated that coping style, self-efficacy, partner's income, family role
      relationship, and cancer risk perception were significant contributors to the
      survivors' and their unaffected relatives' cancer worries. Significant variables
      for perception of cancer risk for both survivors and relatives included income,
      race, family history of cancer, and cancer worries. Relatives had a higher
      perception of cancer risk, whereas survivors had more cancer worries.
      Additionally, the level of cancer worries reported by one member of the dyad was
      related to the amount of worries reported by the other. The results from this
      study underscore the importance of clinicians addressing concerns of both
      affected and unaffected members of families at increased risk of cancer to assist
      them in managing cancer worries and having realistic risk appraisals to make
      informed decisions about their own and their family's health surveillance
      options.

PMID- 18613301
TI  - A new red fluorescent protein that allows efficient marking of murine
      hematopoietic stem cells.
AB  - BACKGROUND: Genetic marking of hematopoietic stem cells (HSCs) with multiple
      fluorescent proteins (FPs) would allow analysis of their features, including
      interaction with adjacent cells. However, there are few red FPs that are
      comparable to green FPs in terms of low toxicity and high fluorescent intensity.
      This study has evaluated the usefulness of Kusabira Orange (KO) originated from
      the coral stone Fungia concinna as a red FP for marking of HSCs METHODS: A vector
      used was the MSCV-type retroviral vector, D Delta Nsap that has the PCC4 cell
      passaged myeloproliferative sarcoma virus derived long terminal repeat devoid of
      a binding site for YY1 and the primer-binding site derived from the dl587rev,
      respectively. The vector was cloned with the codon-optimized KO cDNA for higher
      expression in mammalian cells (huKO) and converted to the corresponding
      retroviruses pseudotyped with the vesicular stomatitis virus G envelope protein,
      then transduced into c-KIT(+)Sca-1(+)Lineage(-) cells obtained from C57BL/6
      (Ly5.1) mice followed by transplantation into lethally irradiated Ly5.2 mice.
      RESULTS: Approximately 70% of donor-derived cells highly expressed huKO at 16
      weeks post-transplantation. Furthermore, the high expression of huKO was also
      detected in serially transplanted mice, suggesting that expression of huKO per se
      had little deleterious effect on murine hematopoiesis. In double marking
      experiments, huKO-expressing hematopoietic cells were easily distinguished from
      those expressing EGFP by flow cytometry and fluorescent microscope analysis.
      CONCLUSIONS: Overall, the results obtained from the present study suggest that
      huKO can be used as a valuable and versatile red fluorescent marker for HSCs.

PMID- 18613302
TI  - Behavioural functioning of retinoblastoma survivors.
AB  - OBJECTIVE: To assess behavioural problems in retinoblastoma (RB) survivors.
      METHODS: This population-based cross-sectional study included 148 RB survivors (8
      35 years), registered in the Dutch national RB register. Survivors and parents
      were asked to fill in behavioural questionnaires. Prevalence rates were computed,
      based on both self-reports and proxy reports. One-sample T-tests were applied to
      analyse differences compared with healthy reference samples. Multiple regression
      analyses were performed to identify predictors for behavioural problems within
      the RB sample. RESULTS: Between-group differences varied across informants and
      across age groups. Parents reported significantly elevated total problem
      behaviour in 30% of their offspring (aged 8-17 years); this against 9% in
      adolescents (12-17 years) and 12% in adults (18-35 years) based on self-report.
      Parental reports showed significantly elevated rates of (1) internalising
      problems in boys and (2) somatic complaints in both girls and boys. Self-reports
      indicate significantly lowered levels of (1) externalising problems in adolescent
      and adult women and (2) thought problems in female adolescents and in adult men.
      Especially survivors who suffered hereditary RB, who had undergone more intensive
      treatment, and who came from a single-parent family were identified to be at most
      behavioural risk. CONCLUSION: Perception of severity and the nature of
      behavioural problems seem to differ between beholder, and to vary between age
      groups, if not between life stages. Health professionals should be aware that
      especially those who are confronted with hereditary RB and who subsequently
      undergo intensive treatment, and who grow up in broken families, run the risk of
      developing behavioural difficulties.

PMID- 18613304
TI  - On boundaries, selectivity, and impact.

PMID- 18613305
TI  - Linear constraint relations in biochemical reaction systems: I. Classification of
      the calculability and the balanceability of conversion rates.
AB  - Measurements provide the basis for process monitoring and control as well as for
      model development and validation. Systematic approaches to increase the accuracy
      and credibility of the empirical data set are therefore of great value. In
      (bio)chemical conversions, linear conservation relations such as the balance
      equations for charge, enthalpy, and/or chemical elements, can be employed to
      relate conversion rates. In a pactical situation, some of these rates will be
      measured (in effect, be calculated directly from primary measurements of, e.g.,
      concentrations and flow rates), as others can or cannot be calculated from the
      measured ones. When certain measured rates can also be calculated from other
      measured rates, the set of equations, the accuracy and credibility of the
      measured rates can indeed be improved by, respectively, balancing and gross error
      diagnosis. The balanced conversion rates are more accurate, and form a consistent
      set of data, which is more suitable for further application (e.g., to calculate
      nonmeasured rates) than the raw measurements. Such an approach has drawn
      attention in previous studies. The current study deals mainly with the problem of
      mathematically classifying the conversion rates into balanceable and calculable
      rates, given the subset of measured rates. The significance of this problem is
      illustrated with some examples. It is shown that a simple matrix equation can be
      derived that contains the vector of measured conversion rates and the redundancy
      matrix R. Matrix R plays a predominant role in the classification problem. In
      supplementary articles, significance of the redundancy matrix R for an improved
      gross error diagnosis approach will be shown. In addition, efficient equations
      have been derived to calculate the balanceable and/or calculable rates. The
      method is completely based on matrix algebra (principally different from the
      graph-theoretical approach), and it is easily implemented into a computer
      program. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613306
TI  - Linear constraint relations in biochemical reaction systems: II. Diagnosis and
      estimation of gross errors.
AB  - Conservation equations derived from elemental balances, heat balances, and
      metabolic stoichiometry, can be used to constrain the values of conversion rates
      of relevant components. In the present work, their use will be discussed for
      detection and localization of significant errors of the following types: 1.At
      least one of the primary measurements has a significant error (gross measurement
      error).2.The system definition is incorrect: a component a.is not included in the
      system description.b.has a composition different from that specified.3.The
      specified variances are too small, resulting in a too-sensitive test.The error
      diagnosis technique presented here, is based on the following: given the
      conservation equations, for each set of measured rates, a vector of residuals of
      these equations can be constructed, of which the direction is related to the
      error source, as its length is a measure of the error size. The similarity of the
      directions of such a residual vector and certain compare vectors, each
      corresponding to a specific error source, is considered in a statistical test. If
      two compare vectors that result from different error sources have (almost) the
      same direction, errors of these types cannot be distinguished from each other.
      For each possible error in the primary measurements of flows and concentrations,
      the compare vector can be constructed a priori, thus allowing analysis
      beforehand, which errors can be observed. Therefore, the detectability of certain
      errors likely to occur can be insured by selecting a proper measurement set. The
      possibility of performing this analysis before experiments are carried out is an
      important advantage, providing a profound understanding of the detectability of
      errors. The characteristics of the method with respect to diagnosis of
      simultaneous errors and error size estimation are discussed and compared to those
      of the serial elimination method and the serial compensation strategy, published
      elsewhere. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613307
TI  - Protein fractionation using fast flow immobilized metal chelate affinity
      membranes.
AB  - A new group-specific affinity membrane using metal chelates as ligands and
      inorganic glass hollow fiber microfiltration membranes as support matrices is
      developed and tested. The study focused on developing the optimum activation and
      coupling procedures to bind the chelating agent (iminodiacetic acid, IDA) to the
      surface of the microporous glass hollow fiber membrane and testing the resultant
      affinity membrane. Starting with three different glass surfaces, five
      modification reactions were evaluated. All the modified "active surfaces" were
      first tested for their protein adsorptive properties in batch mode with suspended
      microporous glass grains using model proteins with known binding characteristics
      with Cu-IDA systems. The metal loading capacities of the surfaces exhibiting
      favorable fractionation were then measured by atomic absorption spectroscopy.The
      results were compared with the results obtained with a commercial material used
      in immobilized metal affinity column chromatography. The protein binding
      characteristics of the hollow fiber affinity membranes were also evaluated under
      conditions of convective flow. This was performed by flowing single solute
      protein solutions through the microporous membrane at different flow rates. These
      results were then used to estimate the optimum loading and elution times for the
      process. A mathematical model incorporating radial diffusion was solved using a
      finite difference discretization method. Comparison between model predictions and
      experimental results was performed for four different proteins at one flow rate.
      These results suggested that the kinetics of adsorption was concentration
      dependent. Finally, the hollow fiber affinity membranes were challenged with two
      component mixtures to test their ability to fractionate mixed protein solutions.
      Efficient separation and good purity were obtained.The results presented here
      represent the development of a new fast flow affinity membrane process
      immobilized metal affinity membranes (IMAM). (c) 1994 John Wiley & Sons, Inc.

PMID- 18613308
TI  - Quantification of damage to suspended insect cells as a result of bubble rupture.
AB  - It is proposed that when cells are either attached to, or very near, a rupturing
      bubble, the hydrodynamic forces associated with the rupture are sufficient to
      kill the cells. Four types of experiments were conducted to quantify the number
      and location of these killed cells. We determined: (1) the number of cells killed
      as a result of a single, 3.5-mm bubble rupture; (2) the number and viability of
      cells in the upward jet that results when a bubble ruptures; (3) the number of
      cells on the bubble film; and (4) the fate of cells attached to the bubble film
      after film rupture. All experiments were conducted with Spodoptera frugiperda (SF
      9) insect cells, in TNM-FH and SFML medium, with and without Pluronic F-68.
      Experiments indicate that approximately 1050 cells are killed per single, 3.5-mm
      bubble rupture in TNM-FH medium and approximately the same number of dead cells
      are present in the upward jet. It was also observed that the concentration of
      cells in this upward jet is higher than the cell suspension in TNM-FH medium
      without Pluronic F-68 by a factor of two. It is believed that this higher
      concentration is the result of cells adhering to the bubble interface. These
      cells are swept up into the upward jet during the bubble rupture process.
      Finally, it is suggested that a thin layer around the bubble containing these
      absorbed cells is the "hypothetical killing volume" presented by other
      researchers. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613309
TI  - Enhanced disruption of Candida utilis using enzymatic pretreatment and high
      pressure homogenization.
AB  - The enhancement of the overall disruption of a native strain of Candida utilis
      (ATCC 9226) was studied using a combination of two methods, namely, pretreatment
      in the form of partial enzymatic lysis by Zymolyase followed by mechanical
      disruption in a Microfluidizer high-pressure homogenizer. The cells were grown in
      both batch and continuous cultures to examine the effect of specific growth rate
      on disruption. Cell suspensions ranging in concentration from 7 to 120 g DW/L
      were disrupted with and without enzymatic pretreatment. For yeast grown in batch
      culture, final total disruption obtained using the combined protocol approached
      95% with four passes at a pressure of 95 MPa, as compared with only 65%
      disruption using only mechanical homogenization. A modified model was developed
      to predict the fraction disrupted by the enzymatic pretreatment-mechanical
      homogenization two-stage process. Predicted disruptions agreed favorably with
      experimental observations (maximum deviation of 20%) over a wide range of
      operating conditions. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613310
TI  - Rapid renaturation of denatured and aggregated proteins using liquid paraffin as
      a pseudolipid bilayer membrane.
AB  - A means of rapidly renaturing denatured protein was devised and evaluated. Three
      liquids were laminarly layered in a centrifuge tube, in which two solutions
      sandwiched liquid paraffin so as to form a pseudolipid bilayer. Denatured and
      aggregted protein placed on the upper surface of liquid paraffin was renatured as
      it passed through liquid-paraffin layer into the renaturation buffer during the
      centrifugation. The aggregated and denatured protein selectively passed through
      the liquid-paraffin layer, whereas other solutions, such as chaotropic agents or
      organic solvent, could not. This means that a rapid dilution condition favorable
      for protein renaturation was realized in a small scale. Aggregated and denatured
      BSA and ribonuclease A were renatured and resolubilized as they passed through
      the liquid-paraffin layer into an appropriate renaturation buffer solution. This
      method was also applied to the rapid heme reconstitution of myoglobin from
      Feprotoporphyrin IX to Zn-protoporphyrin IX. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613311
TI  - Effect of solvent on enantioselective esterification of naproxen by lipase with
      trimethylsilyl methanol.
AB  - Improvement of stereoselective resolution of racemic Naproxen, 2-(6-methoxy-2
      naphthyl)propionic acid, was attempted with esterifcation reaction by Candida
      cylindracea lipase. By carefully selecting the organic medium, a 72-time
      enhancement of yield of the desired S-ester was achieved. The optimal reaction
      temperature was approximately 53 degrees C, and an alcohol concentration between
      20 mM and 40 mM in an 80% (v/v) isooctane and 20% (v/v) toluene mixture was
      found. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613312
TI  - The influence of vessel height and top-section size on the hydrodynamic
      characteristics of airlift fermentors.
AB  - Fermentations of the yeast Saccharomyces cerevisiae were carried out in a 90 to
      250-L working volume concentric tube airlift fermentor. Measurements of liquid
      circulation velocity, gas hold-up, and liquid mixing were made under varying
      conditions of gas flowrate, vessel height, and top-section size. Both liquid
      circulation velocity and mixing time increased with vessel height. Liquid
      velocity varied approximately in proportion to the square root of column height,
      supporting a theoretically based relationship. The effect of vessel height on gas
      hold-up was negligible. The height of the top-section had a significant effect on
      liquid mixing. Mixing time decreased with increasing size of the top-section up
      to a critical height. As the top-section was expanded beyond this height, little
      improvement in mixing was seen. This indicated the presence of a two-zone flow
      pattern in the top-section. Liquid velocity and gas hold-up were essentially
      independent of top-section height. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613313
TI  - Utilization of osmoprotective compounds by hybridoma cells exposed to
      hyperosmotic stress.
AB  - A search was undertaken for osmoprotective compounds for mouse hybridoma cell
      line 6H11 grown in culture. When the osmolality of the growth medium was
      increased above the normal osmolality of 330 mOsmol/kg, growth rates were
      decreased in a dose-dependent fashion, reaching zero when the osmolality of the
      medium reached approx. 435 mOsmol/kg through the addition of KCl (60 mM), or 510
      mOsmol/kg through the addition of NaCl (100 mM), or sucrose (175 mM). For NaCl or
      sucrose-stressed cultures, the inclusion of glycine betaine, sarcosine, proline,
      glycine, or asparagine in the growth medium gave a moderate to strong
      osmoprotective effect, measured as the ability of these compounds to enhance cell
      growth rates under hyperosmotic conditions. Inclusion of dimethylglycine may also
      give a strong osmoprotective effect under these stress conditions.In KCl-stressed
      cell cultures, addition of glycine betaine, sarcosine, or dimethylglycine gave
      strong osmoprotective effects. Of 38 compounds tested during NaCl stress, 7 gave
      weak osmoprotective effects and 25 gave no osmoprotective effect. The
      osmoprotective compounds accumulated inside the stressed cells. Accumulation was
      completed after 4 to 8 h, reaching intracellular concentrations of approx. 0.27
      pmol/cell, or 0.15 M, in NaCl stressed cells (100 mM NaCl added).Glycine betaine,
      dimethylglycine, and sarcosine accumulation was observed only when these
      protectants were included in the medium. For all osmoprotectants, a growth medium
      concentration between 5 and 30 mM gave the maximal protective effect, with the
      exception of dimethylglycine, for which the optimum concentration was approx. 65
      mM. Osmoprotective effects obtained with glycine, sarcosine, dimethylglycine, and
      glycine betaine, indicate that the more methylated compounds are the most
      effective protectants.The cellular content of glycine betaine and the glycine
      betaine uptake rate increased with medium osmolality in a linear fashion. Glycine
      betaine uptake was described by a model comprising a saturable component obeying
      Michaelis-Menten kinetics and a nonsaturable component. K(m) and V(max) for
      glycine betaine uptake were determined at 420 mOsmol/kg (50 mM NaCl added) and
      510 mOsmol/kg (100 mM NaCl added). A K(m) value of approx. 2.5 mM was obtained at
      both medium osmolalities, while V(max) increased from 0.010 pmol/cell . h to
      0.018 pmol/cell . h as the osmolality of the growth medium was increased,
      indicating an effect of medium osmolality on the maximal rate of transport rather
      than on the affinity of the transporters for glycine betaine. Hybridoma cells
      were not able to utilize the glycine betaine precursors choline or glycine
      betaine aldehyde for osmoprotection, suggesting that the cells lack part, or all,
      of the choline-glycine betaine pathway or the appropriate uptake mechanism.The
      uptake rate for glycine in NaCl-stressed hybridoma cells was approx. four times
      higher than the uptake rate for glycine betaine. Furthermore, if equimolar
      amounts of glycine betaine, glycine, sarcosine, and proline were simultaneously
      added to NaCl-stressed cell cultures, the intracellular concentrations of
      glycine, proline, and sarcosine were significantly higher than the concentration
      of glycine betaine.A 40% increase in hybridoma cell volume was observed when the
      growth medium osmolality was increased from 300 to 520 mOsmol/kg. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18613314
TI  - A cellular automaton model for microcarrier cultures.
AB  - In order to achieve high cell densities anchoragedependent cells are commonly
      cultured on microcarriers, where spatial restrictions to cell growth complicates
      the determination of the growth kinetics. To design and operate large-scale
      bioreactors for microcarrier cultures, the effect of this spatial restriction to
      growth, referred to as contact inhibition, must be decoupled from the growth
      kinetics. In this article, a cellular automaton approach is recommended to model
      the growth of anchorage-dependent cells on microcarriers. The proposed model is
      simple to apply yet provides an accurate representation of contact-inhibited cell
      growth on microcarriers. The distribution of the number of neighboring cells per
      cell, microcarrier surface areas, and inoculation densities are taken into
      account with this model. When compared with experimental data for Vero and MRC-5
      microcarrier cultures, the cellular automaton predictions were very good.
      Furthermore, the model can be used to generate contact-inhibition growth curves
      to decouple the effect of contact-inhibition from growth kinetics. With this
      information, the accurate determination of kinetic parameters, such as nutrient
      uptake rates, and the effects of other environmental factors, such as toxin
      levels, may be determined. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613315
TI  - Increased thermostability of Asn182 --> Ala mutant Aspergillus awamori
      glucoamylase.
AB  - Asn182 --> Ala Aspergillus awamori glucoamylase expressed in Saccharomyces
      cerevisiae had a first-order thermodeactivation coefficient 40% that of wild-type
      glucoamylase at pH 4.5 between 60 degrees and 65 degrees C, caused by the
      elimination of an Asn-Gly sequence subject to deamidation and eventual chain
      breakage. Above 70 degrees C, and at pHs 3.5 and 5.5, thermodeactivation
      coefficients of wild-type and mutant enzymes were roughly equal, because the
      fastest deactivation mechanism was no longer deamidation. The mutation had little
      effect on the enzyme's optimal pH for activity and subsite map, or on the glucose
      yield from starch dextrin hydrolysis. During enzyme production by yeast
      fermentation, highest cell densities and activities of wild-type and mutant
      glucoamylases were attained after a period of glucose starvation, followed by a
      second addition of glucose. (c) 1994 John Wiley & Sons, Inc.

PMID- 18613316
TI  - Parental response to health risk information: experimental results on willingness
      to-pay for safer infant milk formula.
AB  - Enterobacter sakazakii, a pathogen that can be found in powdered infant milk
      formula, can cause adverse health effects on infants. Using Vickrey auction, this
      study examines parents' willingness to pay (WTP) for a quality assurance label on
      powdered infant milk formula. The influence of ambiguity with the incidence rate
      information and provision of safe-handling information on WTP are also evaluated
      using three experimental treatments. Our findings generally imply that parents
      significantly value a quality assurance label. The mean price premium parents are
      willing to pay for the safer and quality assurance labelled powdered infant milk
      formula ranges from 61 to 133 Eurocents per 100 grams (53-116% of the base price
      per 100 grams) depending on the treatment. While no ambiguity effects are
      generally found, provision of safe-handling information significantly reduced WTP
      to 39-69 Eurocents per 100 grams depending on the treatment.

PMID- 18613317
TI  - Physician labour supply in Canada: a cohort analysis.
AB  - This paper employs a cohort analysis to examine the relative importance of
      different factors in explaining changes in the number of hours spent in direct
      patient care by Canadian general/family practitioners (GPs) over the period 1982
      2003. Cohorts are defined by year of graduation from medical school. The results
      for male GPs indicate that there is little age effect on hours of direct patient
      care, especially among physicians aged 35-55, there is no strong cohort effect on
      hours of direct patient care, but there is a secular decline in hours of direct
      patient care over the period. The results for female GPs indicate that female
      physicians on average work fewer hours than male physicians, there is a clear age
      effect on hours of direct patient care, there is no strong cohort effect, and
      there has been little secular change in average hours of direct patient care. The
      changing behaviour of male GPs accounted for a greater proportion of the overall
      decline in hours of direct patient care from the 1980s through the mid-1990 s
      than did the growing proportion of female GPs in the physician stock.

PMID- 18613318
TI  - On the positive relation between received social support and negative affect: a
      test of the triage and self-esteem threat models in women with breast cancer.
AB  - OBJECTIVE: There is a seemingly paradoxical positive relation between received
      social support and psychological distress in cancer patients. This study
      evaluates two models that explain this positive relation: (a) the triage model,
      which argues that more distressed people receive more support and (b) the self
      esteem threat model, which argues that receiving support increases distress by
      undermining self-esteem. METHODS: Longitudinal survey data were collected from 71
      women treated for breast cancer at 3- (T1) and 18-months (T2) post-diagnosis.
      RESULTS: Analyses did not disconfirm either model. Consistent with the triage
      model, there was a marginally significant (p=0.052) positive relation between T1
      negative affect and T2 received support, controlling for T1-received support.
      Consistent with the self-esteem threat model, a significant positive relation
      between T1 received support and T2 negative affect, controlling for T1 negative
      affect, appeared to be mediated by T2 self-esteem. CONCLUSIONS: These findings
      suggest that people with cancer who are most distressed may receive the most
      social support, but the conveyance of support can have negative consequences for
      self-esteem and affect.

PMID- 18613320
TI  - South African court bans vitamin trials for HIV/AIDS.

PMID- 18613319
TI  - A randomized trial of a breast/ovarian cancer genetic testing decision aid used
      as a communication aid during genetic counseling.
AB  - OBJECTIVES: To evaluate the impact of a decision aid for women considering
      genetic testing for breast/ovarian cancer risk given during genetic counseling.
      METHODS: One hundred and forty-eight women were randomized to receive the
      decision aid or a control pamphlet at the beginning of their first consultation
      with a genetic counselor. When the patient received the decision aid, it was used
      to complement consultation discussions about genetic testing. One hundred and ten
      (74.3%) women completed the first questionnaire designed to elicit information
      about women's levels of decisional conflict and knowledge about genetic testing.
      Of these, 105 (70.9%) completed a second questionnaire to assess longer-term
      outcomes, 6 months postconsultation. RESULTS: Results showed that women who
      received the decision aid felt more informed about genetic testing
      (chi(2)(1)=8.69; P=0.003), had clearer values (chi(2)(1)=6.90; P=0.009) and had
      higher knowledge levels (chi(2)(2)=6.49; P=0.039) than women who received the
      control pamphlet. CONCLUSIONS: The developed decision aid improved patient
      outcomes better than a control pamphlet when implemented during genetic
      counseling and given to the patient to take home.

PMID- 18613321
TI  - Controlling Chagas' disease in urban Peru.

PMID- 18613322
TI  - Indigenous health in Australia still lagging.

PMID- 18613323
TI  - John Snow: the making of a hero?

PMID- 18613324
TI  - [Metformin, fifty years since the arrival of this molecule!].

PMID- 18613325
TI  - Metformin as first choice in oral diabetes treatment: the UKPDS experience.
AB  - Metformin has been used successfully since the 1950s as first line
      pharmacotherapy to treat people with type 2 diabetes. It is a biguanide that
      decreases blood glucose concentration by mechanisms different from those of
      insulin secretagogues, such as sulphonylureas, or exogenous insulin therapy.
      Metformin lowers, rather than increases, fasting plasma insulin concentrations
      and acts by enhancing insulin sensitivity, inducing greater peripheral uptake of
      glucose, and decreasing hepatic glucose output. By reducing hepatic glucose
      output it lowers blood glucose and insulin levels with minimal risk of
      hypoglycaemia, and when used as monotherapy can lower HbAlc by around 1.5%. It is
      usually well tolerated, the most common side effects being gastrointestinal. Of
      particular value is that the improved glucose control seen with metformin is
      achieved without weight gain. Concerns that it may increase the risk of lactic
      acidosis have largely been allayed with recent studies suggesting less than one
      case per 100,000 treated patients. The UK Prospective Diabetes Study (UKPDS)
      demonstrated a substantial beneficial effect of metformin therapy on
      cardiovascular disease (CVD) outcomes, with a 36% relative risk reduction in all
      cause mortality and a 39% relative risk reduction in myocardial infarction . The
      first ever joint ADA (American Diabetes Association) and EASD (European
      Association for the Study of Diabetes) consensus guidelines on the management of
      hyperglycaemia in type 2 diabetes state explicitly that metformin should be used
      as first-line foundation therapy, in addition to lifestyle interventions.

PMID- 18613326
TI  - [Systemic inflammatory response syndrome and anti-endotoxin immunity after the
      operations on the abdominal cavity organs].
AB  - The blood plasma level of albumin, C-reactive protein, common and specific
      antiendotoxinal immunoglobulins (Ig) was investigated in 52 patients after
      performance of large operations on the abdominal cavity organs. On the third
      postoperative day the blood concentration of albumin and antiendotoxinal Ig was
      low, while of C-reactive protein-high. It must be concluded, that the systemic
      inflammatory answer syndrome occurrence and the antiendotoxinal immunity
      inhibition after the operation are caused by the microorganisms translocation and
      interaction of specific antibodies with endotoxin.

PMID- 18613327
TI  - [Peculiarities of laparoscopic diagnosis of the closed hepatic traumatic damage].
AB  - Diagnostic possibilities of laparoscopy were studied in 24 injured persons,
      suffering closed hepatic damage in noninformity of results of clinical,
      laboratory-biochemical, roentgenologic, ultrasound investigations and diagnostic
      peritoneal lavage as well, were studied. Isolated trauma was revealed in 8
      injured persons, the multiple one in 7 and the combined--in 9. Open operation was
      performed in 21 patients, relaparotomy--in 3, laparoscopic intervention with
      curative intent--in 3 hepatic wound tamponade, using hemostatic sponge with
      ambene, lubricated by dicinon. Three patients died due to severe combined trauma.

PMID- 18613328
TI  - [The studying of mechanical properties of endoexpander for optimization of the
      tissues expanding method].
AB  - The standing ground investigation of mechanical properties of the silicone
      expander of own construction was conducted for determination of its physical load
      on adjacent tissues while their expanding performing. There was established, that
      the tissues expanding over the expanders occurs in a logarithmic mode. The data
      obtained permit to model and estimate the expanding process components on all its
      stages.

PMID- 18613329
TI  - "Texas Medicaid is going to have to do a lot better before I will see anyone in
      my office." Neither is he.

PMID- 18613330
TI  - [Barriers of fortune].

PMID- 18613332
TI  - Prevention.  Groups vow to end ban on clean-needle funding.

PMID- 18613333
TI  - Global.  Congress poised to debate expansion of PEPFAR funding.

PMID- 18613334
TI  - 6-month limit for PTSD over AIDS needlestick reversed.

PMID- 18613335
TI  - Discrimination.  Foreign Service ends HIV discriminatory employment policy.

PMID- 18613336
TI  - Discrimination.  HIV-positive university employee's termination affirmed.

PMID- 18613337
TI  - Asylum.  HIV-positive immigrant's persecution claim rejected.

PMID- 18613338
TI  - Dismissal of doctor's discrimination claim affirmed.

PMID- 18613339
TI  - Policy.  University halts blood drives, cites donation discrimination.

PMID- 18613340
TI  - Occurrence of contaminant accumulation in lead pipe scales from domestic drinking
      water distribution systems.
AB  - Previously, contaminants, such as AI, As, and Ra, have been shown to accumulate
      in drinking-water distribution system solids. Accumulated contaminants could be
      periodically released back into the water supply causing elevated levels at
      consumers taps, going undetected by most current regulatory monitoring practices
      and consequently constituting a hidden risk. The objective of this study was to
      determine the occurrence of over 40 major scale constituents, regulated metals,
      and other potential metallic inorganic contaminants in drinking-water
      distribution system Pb (lead) or Pb-lined service lines. The primary method of
      analysis was inductively coupled plasma-atomic emission spectroscopy, following
      complete decomposition of scale material. Contaminants and scale constituents
      were categorized by their average concentrations, and many metals of potential
      health concern were found to occur at levels sufficient to result in elevated
      levels at the consumer's taps if they were to be mobilized. The data indicate
      distinctly nonconservative behavior for many inorganic contaminants in drinking
      water distribution systems. This finding suggests an imminent need for further
      research into the transport and fate of contaminants throughout drinking-water
      distribution system pipes, as well as a re-evaluation of monitoring protocols in
      order to more accurately determine the scope and levels of potential consumer
      exposure.

PMID- 18613341
TI  - Cohesion, Alliance, and outcome in group psychotherapy: comments on Joyce et al.
      (2007) and Johnson (2007).

PMID- 18613342
TI  - Nutrition in clinical practice. Gastrointestinal disorders and their connections
      to nutrition.

PMID- 18613343
TI  - Soil-transmitted helminthiasis. Progress report on number of children treated
      with anthelminthic drugs: an update towards the 2010 global target.

PMID- 18613344
TI  - Preventing sudden death: implantable cardioverter-defibrillators in elderly
      cardiac patients.
AB  - Much of the public was introduced to the implantable cardioverter-defibrillator
      (ICD) when Vice President Cheney, a survivor of four heart attacks, received the
      device in 2001. Although ICDs were initially limited to patients with previous
      cardiac arrests or arrhythmias, more recent studies have demonstrated that ICDs
      can prevent sudden cardiac death in patients who have not had a cardiac arrest,
      but are at greater risk for one (for example, those with congestive heart failure
      and reduced cardiac function). This Issue Brief summarizes studies that analyze
      health outcomes, costs, and quality of life for patients-at-risk who receive ICDs
      in real-life settings.

PMID- 18613345
TI  - Abstracts of the 5th Research Forum of the European Association for Palliative
      Care (EAPC). Trondheim, Norway. May 28-31, 2008.

PMID- 18613346
TI  - Abstracts of the 7th Palliative Care Congress. Glasgow, Scotland, United Kingdom.
      April 29-May 1, 2008.

PMID- 18613347
TI  - [Potential nasal transepithelial difference].

PMID- 18613348
TI  - What if the ATN trial...?

PMID- 18613349
TI  - Calculating left ventricular end diastolic pressure from Doppler
      echocardiography.

PMID- 18613350
TI  - Regarding "Post-mortem ocular changes".

PMID- 18613351
TI  - Criminal records review.

PMID- 18613352
TI  - An overlooked lesion of the anorectal junction: cloacogenic polyp.

PMID- 18613353
TI  - Palisading longitudinal esophagus vessels at esophago-gastric junction.
AB  - BACKGROUND/AIMS: Endoscopically, as a marker of the EGJ (Esophago-gastric
      Junction), the most distal end of the palisading longitudinal esophagus vessels
      (PLEVs) is useful. The aim of this study is to clarify the origin of PLEVs.
      METHODOLOGY: The present study included 10 patients who underwent esophagectomy
      and proximal gastrectomy. Vascular injection of radiopaque medium was performed
      for fresh resected specimens. Subsequently, specimens were opened longitudinally,
      pinned on a corkboard, and fixed overnight in 4% buffered formaldehyde. Injected
      vessels were simultaneously examined macroscopically, radiographically, and
      histopathologically. The injection medium consisted of liquid barium (providing
      radiopacity), 3% agarose gel (1g/100 mL H2O, providing stability) and carmin
      (providing macroscopical visibility with red color). Five cases were performed
      via veins and the other 5 cases via arteries. RESULTS: All vein-injected and
      longitudinally-opened specimens showed PLEVs around EGJ. Red color stained thin
      vessels were superficially recognized at almost the same density of vascularity
      as radiopraphically examined vessels. Macroscopic and radiographic images were
      easily superimposed concoding PLEVs and EGJ. On the other hand, there are no
      cases demonstrating PLEVs by artery-injected images. Histopathologically, PLEVs
      were apparent in the lamina propria mucosae just above muscularis mucosae. PLEVs
      penetrate obliquely from oral to distal in the submucosa at EGJ. PLEVs were
      positive for CD31 but negative for D2-40. CONCLUSIONS: PLEVs are the stream of
      superficial veins, not arteries.

PMID- 18613354
TI  - Should all splenectomised patients be vaccinated to avoid OPSI? Revisiting an old
      concept: an Italian retrospective monocentric study.
AB  - BACKGROUND/AIMS: [corrected] The aims of this study were to evaluate the
      incidence of overwhelming postsplenectomy infection (OPSI), the usefulness of
      vaccination in preventing OPSI, and whether affected patients had received the
      current best practice preventive measures. METHODOLOGY: The patients, observed
      from June 1991 to May 2005, were reviewed retrospectively. Gender, age, causes of
      splenectomy, vaccinations and complications were studied. RESULTS: 225 patients
      (178 males, 47 females) underwent splenectomy, and of these, 79 patients (35.1%)
      were considered for the present study. Seven patients (8.8%) were informed about
      the risks of infection and received pneumococcal polysaccharide vaccine after
      splenectomy. Sixty-eight patients (86.7%) receive influenza vaccine every year.
      One of the patients that did not receive immunoprophylaxis had OPSI (incidence
      1.26%) 1 year after splenectomy. CONCLUSION: Vaccination seems to prevent OPSI.
      Because of low incidence of OPSI, however, prospective randomised studies in
      patients without risk factors are needed to evaluate the usefulness of
      immunoprophylaxis.

PMID- 18613355
TI  - Application of Six Sigma towards improving surgical outcomes.
AB  - BACKGROUND/AIMS: Six Sigma is a 'process excellence' tool targeting continuous
      improvement achieved by providing a methodology for improving key steps of a
      process. It is ripe for application into health care since almost all health care
      processes require a near-zero tolerance for mistakes. The aim of this study is to
      apply the Six Sigma methodology into a clinical surgical process and to assess
      the improvement (if any) in the outcomes and patient care. METHODOLOGY: The
      guiding principles of Six Sigma, namely DMAIC (Define, Measure, Analyze, Improve,
      Control), were used to analyze the impact of double stapling technique (DST)
      towards improving sphincter preservation rates for rectal cancer. RESULTS: The
      analysis using the Six Sigma methodology revealed a Sigma score of 2.10 in
      relation to successful sphincter preservation. This score demonstrates an
      improvement over the previous technique (73% over previous 54%). CONCLUSIONS:
      This study represents one of the first clinical applications of Six Sigma in the
      surgical field. By understanding, accepting, and applying the principles of Six
      Sigma, we have an opportunity to transfer a very successful management philosophy
      to facilitate the identification of key steps that can improve outcomes and
      ultimately patient safety and the quality of surgical care provided.

PMID- 18613356
TI  - Acute necrotizing pancreatitis: intra-abdominal vacuum sealing after
      necrosectomy.
AB  - BACKGROUND: Cases of acute pancreatitis with infected pancreatic necrosis warrant
      consideration of surgical interventions designed to achieve the goal of
      pancreatic debridement and drainage. Notable experience with the use of vacuum
      assisted closure for abdominal wall defects was an assumption for its
      peripancreatic application after debridement in septic patients with infected
      pancreatic necrosis confirmed by radiological evidence of gas or results of fine
      needle aspiration. The goal of this study was to evaluate our own experience with
      this new therapeutic technique. METHODS: This study is a multi-center
      retrospective analysis and comparison of 2 groups of patients with severe sepsis
      and a proven pancreatic source of infection. Group A consisted of 67 patients, 42
      men and 25 women with ages ranging from 19-90 years (mean 48.0), who were treated
      surgically between 2002 and 2006 using a combination of laparostomy, multiple
      irrigations and abdominal drainage. Group B consisted of 39 patients, 28 men and
      11 women aged from 18-87 years (mean 51.8), who were treated between 2002 and
      2006 using the former techniques with the addition of an intra-abdominal vacuum
      assisted negative pressure therapy system. RESULTS: The number of repeat
      laparotomies with debridement of the open abdominal wound in general anesthesia
      in group A ranged from 5-18 over 10-33 days (median 21) of surgical treatment
      period. The number of repeat laparotomies in group B decreased to 3-9 and the
      surgical treatment period decreased to 9-29 days (median 16). Seventeen patients
      (25.4%) in group A died because of severe sepsis and multiple organ failure,
      compared to 7 patients (17.9%) in group B. CONCLUSION: Authors confirmed
      significant reduction of morbidity and mortality with the use of the intra
      abdominal vacuum assisted system in the treatment of localized pancreatic source
      of sepsis.

PMID- 18613357
TI  - Pancreatico-jejunostomy with a biodegradable pancreatic stent and without
      stitches through the pancreas.
AB  - Previous experimental studies have shown that multiple puncturing and stitching
      of the pancreas results in an increased pancreatic injury response. Furthermore,
      post-operative pancreatitis, which still is a largely under-diagnosed condition,
      appears to be an important mediator of many post-operative complications after
      pancreatic head resection. Stenting has been suggested to improve both short-term
      and long-term outcome after pancreaticojejunostomy. We have recently developed a
      biodegradable, radiopaque self-expanding stent, which has experimentally been
      shown suitable for pancreatobiliary applications. In this pilot study we tested
      the new technique for pancreatico-jejunostomy in 3 patients. In this novel
      anastomosis technique with a biodegradable stent the pancreatic stump is first
      sunk into the jejunum and tightened with a purse string in the bowel serosa,
      without any stitches through the pancreatic tissue, and the patency of the
      pancreatic duct is secured with a biodegradable stent against the compression of
      the tightened purse-string. The creation of anastomosis was possible as planned
      in all 3 patients. They all recovered without complications. The stent was seen
      in x-ray in all 3 during hospitilization, was found to have disappeared by 1
      month in 2 patients, but was still in place at 3 months in 1 patient. The initial
      experiences described herein encourage progression to a phase I safety study, and
      later possibly to a phase II randomized trial to test the efficacy of the new
      method.

PMID- 18613358
TI  - Magnetic resonance cholangiopancreatography: potential usefulness of
      dehydrocholic acid (DHCA) administration in the evaluation of biliary disease.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous
      dehydrocholic acid (DHCA) was useful to enhance the delineation of the biliary
      tree. METHODOLOGY: Our study population comprised 14 patients. Magnetic resonance
      cholangiopancreatography was acquired before and after the administration of
      DHCA. Two different MRCP snap shot techniques were applied: thick-slab two
      dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and
      multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted
      sequences with three-dimensional (3D) maximum intensity projection (MIP) post
      processing. Volume rendering was prepared based on the source images, and the
      pixel size was visually adjusted to the biliary area of MRCP to measure the
      biliary tree volume. RESULTS: DHCA increased the bile duct volume in 13 of the 14
      patients. It provided a better visualization of the biliary tree in 11 patients.
      The three patients without improvement in visualization included 1 patient with
      liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation
      and 2 patients with cholecystectomy who had the bile ducts filled with bile by
      the time of the administration. CONCLUSIONS: It was suggested that administration
      of DHCA could enhance the delineation of the biliary tree on MRCP images.

PMID- 18613359
TI  - Carcinoma arising in congenital choledochal cysts.
AB  - BACKGROUND/AIMS: Congenital choledochal cyst is almost always associated with
      pancreaticobiliary maljunction and is sometimes associated with biliary
      carcinoma. This study aimed to investigate the clinicopathological features and
      surgical treatment of choledochal cyst associated with carcinoma arising in the
      cyst wall. METHODOLOGY: Relationship of the clinicopathological findings and
      surgical treatment of 8 patients with histologically proven carcinoma that had
      developed in the choledochal cyst wall were examined to determine mode of tumor
      spread, multicentric tumor origins, and coincidence with other neoplastic
      lesions. RESULTS: Papillary adenocarcinoma (n = 5) had different
      clinicopathological features than tubular adenocarcinoma (n = 3). Radiologically,
      papillary adenocarcinoma presented as an eccentrically located polypoid mass in
      the cyst, while with tubular adenocarcinoma, there was evidence of bile duct
      stenosis with irregular thickening of the bile duct wall. Papillary
      adenocarcinoma was associated with extensive superficial spread (n = 1),
      synchronous (n = 2), or metachronous (n = 2) multicentric tumors.
      Pancreatoduodenectomy with (n = 1) or without (n = 1) hepatic lobectomy, and
      repeated resection by hepatic lobectomy (n = 2) were performed for these
      circumstances of tumors. Extensive or repeated resections allowed 3 patients to
      live longer than 2 years. Tubular adenocarcinoma was associated with scirrhously
      infiltrative spread and a poor prognosis. CONCLUSIONS: Papillary adenocarcinoma
      frequently occurs in the choledochal cyst wall. Since aggressive resection offers
      survival benefits in papillary adenocarcinoma arising in the choledochal cyst
      wall, the presence of superficial spread and multicentric tumors should be
      identified and taken into account when planning surgery. Patients require close
      monitoring so that recurrent carcinoma of the remnant bile duct can be identified
      early.

PMID- 18613360
TI  - Hypointense gallbladder on MR cholangiopancreatography.
AB  - A few patients show a gallbladder of poor visibility on magnetic resonance
      cholangiopancreatography (MRCP) images due to various reasons. A 45-year-old man
      was referred with abdominal pain and fever. In contrast enhanced computed
      tomography, several calcified gallstones were observed in the gallbladder.
      Although a solitary calcified stone was seen in the neck of the gallbladder,
      neither stones in the common bile duct (CBD) nor dilatation of CBD were observed.
      On MRCP, hypointense gallbladder with no filling defect in the CBD was observed.
      Histopathological analysis of the gallbladder, which was obtained by laparoscopic
      cholecystectomy, confirmed severe chronic cholecystitis with several calcified
      gallstones up to 0.5 cm in diameter. In conclusion, the finding of hypointense
      gallbladder on MRCP in patients with cholecystitis and its underlying condition,
      though rare, should be kept in mind.

PMID- 18613361
TI  - Long-term outcome of combined liver-kidney transplantation: a single-center
      experience in China.
AB  - BACKGROUND/AIMS: To evaluate patient survival with combined liver-kidney
      transplantation (CLKT) and to identify factors of death in these patients.
      METHODOLOGY: Among 554 cases of liver transplantations (LTs) performed between
      January 1999 and October 2006, there were 19 cases (3.43%) of CLKT recipients. To
      compare the patient survival, 50 matched LT patients out of these patients were
      analyzed retrospectively. Furthermore, causes of death in CLKT patients were
      investigated. RESULTS: Within a mean follow-up of 25.2 months (range 1-96
      months), 7 CLKT patients had died (mortality: 36.8%). There were 4 (21.1%) that
      died in hospital within 1 month, and 3 late mortality cases (deceased after
      hospital discharge). Actuarial survival was 73.7% at 1 year, 59.5% at 3 years,
      and 59.5% at 5 years. Cumulative patient survival was significantly worse among
      CLKT patients compared with LT patients. After excluding patients who died during
      the first month in the 2 groups, cumulative patient survivals were comparable
      between the 2 groups. The survival rate in CLKT patients was 87.5% at 1 year,
      70.7% at 3 years, and 70.7% at 5 years. CONCLUSIONS: CLKT has relatively high
      hospital mortality as compared to LT. Beyond the hospital discharge, however, the
      long-term survival does not differ from LT.

PMID- 18613362
TI  - Ascorbate inhibits apoptosis of Kupffer cells during warm ischemia/reperfusion
      injury.
AB  - BACKGROUND/AIMS: This study sought to determine whether ascorbate (Asc), a
      scavenger of reactive oxygen species, inhibits apoptosis of hepatic cells
      consisting of hepatocytes, Kupffer cells, and sinusoidal endothelial cells (SECs)
      in the rat liver after warm ischemia/reperfusion (I/R) injury. METHODOLOGY:
      Hepatic warm ischemia (69% of the total liver) was induced for 30 min, followed
      by reperfusion for 60 min. In some animals, ascorbate (at 1 or 10 mg/kg) was
      infused intravenously immediately before the onset of reperfusion. Hepatic cell
      apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling (TUNEL). Mitochondrial release of cytochrome c into the
      cytoplasm was assessed by Western blot analysis, and the activation of caspase-3
      in liver tissue was determined by colorimetric assays. RESULTS: Assays of
      cytochrome c release and caspase-3 showed increased levels of these apoptotic
      related proteins and enzyme activity. While few apoptotic hepatocytes or SECs
      were detected in the ischemic group by TUNEL staining, the number of TUNEL
      positive Kupffer cells was approximately 4.5-fold greater than that seen in the
      sham-treatment group. Ascorbate treatment reduced this increase in apoptotic
      Kupffer cells. CONCLUSION: The hepatic cells most vulnerable to oxidative stress
      in the first hour of reperfusion were Kupffer cells. These may play a key role in
      hepatic warm I/R injury.

PMID- 18613363
TI  - Correlation between expression of cyclooxygenase-2 and the presence of CD4+
      infiltrating T-lymphocyte in human primary hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Recent studies have found that Cyclooxygenase-2(Cox-2) is
      frequently inappropriately expressed in primary hepatocellular carcinoma (HCC),
      suggesting that abnormal Cox-2 expression plays an important role in
      hepatocarcinogenesis. But it remains controversial in these reports. Moreover,
      there are only a few studies on the correlation between Cox-2 and infiltrating
      immunocytes in the tumor-microenvironment. CD4+ tumor-infiltrating lymphocytes
      (TIL) and infiltrating immunocytes around the tumor are closely correlated to the
      development of the tumor, but so far no reports are available showing the
      relationship among Cox-2, CD4+ TIL of tumor and CD4+ infiltrating T-lymphocytes
      of adjoining non-tumorous (ANT) tissues in tumor-microenvironment. This study is
      designed to appropriately select and collect patients' specimens to better
      reflect Cox-2 expression in human HCC, and also to stress the correlation among
      Cox-2, CD4+ TIL and CD4+ infiltrating T-lymphocytes in the tumor
      microenvironment. METHODOLOGY: Tumor tissue, and its matched ANT tissue removed
      less than 1 cm from the solid tumor border, were obtained from 25 HCC patients
      all of whom came from Hunan province, China, and were infected with hepatitis B
      virus (HBV). Normal liver tissues of 10 hemangiomas were collected as controls.
      Both Cox-2 expression and the number of CD4+ TIL and CD4+ infiltrating T
      lymphocyte were detected by immunohistochemistry, and data were analyzed closely
      with patients' clinical figures so as to investigate the correlation between the
      3 elements. RESULTS: In 25 HCC patients, remarkably higher Cox-2 expression in
      both tumor and ANT tissues was observed compared with normal liver tissues (p <
      0.001). The percentage of Cox-2 positive cells was, remarkably, higher in ANT
      tissues than in tumors (p < 0.001). Similarly the distribution of CD4+ T cells
      was significantly higher in ANT tissue than in tumor tissue (p < 0.0001), and
      also significantly higher in tumor tissue than in normal tissue (p < 0.0001).
      Importantly, in the group of patients with Cox-2-expressing tumors, the number of
      CD4+ infiltrating T-lymphocyte in ANT tissues was 79.4(+)9.92/hpf, which is
      obviously lower (p = 0.019) than that of the group with non-Cox-2-expressing
      tumors with the number of CD4+ infiltrating T-lymphocyte in ANT tissues at
      118.13(+)12.47/hpf. Cox-2 expression of tumors showed a significant negative
      correlation with number of CD4+ infiltrating T cells of ANT tissues (r = 0.499, p
      = 0.024). The number of CD4+ TILs are lower in Cox-2-expressing tumors than in
      non-Cox-2-expressing tumors, but there was not statistical significance (p =
      0.057). CONCLUSIONS: Taken together we suggest in the tumor-microenvironment of
      HCC the expression of Cox-2 may inhibit the number CD4+ infiltrating T-lymphocyte
      in ANT tissues. As a result, Cox-2 overexpression may contribute to both
      suppression of local immune responses and enhancement of metastatic potential in
      human HCC.

PMID- 18613364
TI  - Laterally spreading tumors--experience based on 138 consecutive cases.
AB  - BACKGROUND/AIMS: Laterally spreading tumors (LST) are flat elevated neoplastic
      lesions with diameters equal to or greater than 10 mm. The treatment results of
      138 lesions in 131 patients are presented here as a part of a retrospective
      analysis. METHODOLOGY: Two gastroenterology centers participated in the study in
      the period from 1/2002-12/2006. During colonoscopy, each superficial lesion was
      classified according to the Paris endoscopic classification. Endoscopic mucosal
      resection (EMR) lift and cut was employed. Treatment was considered successful
      when both endoscopic and histo-pathological criteria of complete resection were
      fulfilled. RESULTS: A total of 138 LST in 131 patients were diagnosed. Average
      LST diameter was 25 mm. A total of 5 (3.6%) lesions in 4 patients were referred
      for primary surgery. One patient was treated with argon plasma coagulation only.
      EMR was attempted for 132/138 (95.7%) of all LST and was successful in 125
      (90.6%) cases. Complications occured in 16/132 (12.1%) patients. Severe
      complications, defined as decession, emergency surgery, emergency endoscopy and
      transfusion of eryhrocyte concentrate occured in 5/132 (3.8%). One (0.7%) 69 year
      old-male patient died on the third day following EMR due to complications of
      acute myocardial infarction. CONCLUSION: LST lesions could be efficiently treated
      with EMR lift and cut method with a reasonable rate of complications.

PMID- 18613365
TI  - Harmonic scalpel in transanal microsurgery.
AB  - BACKGROUND/AIMS: Retrospective clinical study of patients with rectal tumors
      treated by transanal endoscopic microsurgery (TEM) using Ultracision. METHODS:
      From 1997-2006 54 patients were treated by excision of the rectal tumors situated
      in the middle and distal portion, using the harmonic scalpel. We treated 25 male
      (range 40-76 years) and 29 female (range 46-80 years) patients. Tumors were
      benign or well or moderately differentiated carcinomas in stage T1N0M0 or T2N0M0.
      Excision was done by Ultracision (UltraCision, Ethicon Endo-Surgery) to all
      patients. Preoperative examinations were: colonoscopy, biopsy, tumor markers, CT,
      transanal ultrasound, pelvic NMR, gynecological exam in females. The tumors were
      excised by harmonic scalpel after submucosal infiltration of adrenalin (1: 200
      000) and 2% lidocaine. RESULTS: There was no morbidity or mortality in this group
      of patients. Histopathology was: Adenoma tubovillosum in alteratio maligna 20,
      adenocarcinoma (T1N0M0) 6, (T2N0M0) 8, adenocarcinoma with lymphatic vessels and
      perineural spaces invasion 1, adenoma villosum 12 and adenoma tubulare 7. After
      surgical treatment 8 patients underwent adjuvant radiotherapy. There was no local
      recurrence during this period. CONCLUSIONS: TEM is a method of choice in the
      treatment of rectal benign tumors and malignant tumors in stage T1N0M0, grade 1
      and 2. Harmonic scalpel provides a safer, easier, and more precise surgical
      section through clean, bloodless and better visualized operative field.

PMID- 18613366
TI  - Successful treatment for a patient with hemophagocytic syndrome after a small-for
      size graft liver transplantation.
AB  - Hemophagocytic syndrome (HPS) is a hematological disorder caused by activated T
      lymphocytes, which leads to the proliferation of stimulated macrophages that
      phagocytose and destroy circulating blood elements and their precursors within
      bone marrow, and lead to the further production of inflammatory cytokines. Living
      donor liver transplantation (LDLT) between adults has been performed to
      compensate for the shortage of available organs. There have been some reports
      concerning HPS after LDLT; however, its prognosis is disappointingly poor. In
      particular, there is no report of treated HPS developed after LDLT using small
      for-size left lobe grafts. We herein report a case of HPS in a 63-year old woman
      who underwent LDLT using left lobe graft weighing only 330g. The HPS was
      diagnosed on postoperative day 13, and was successfully treated using a
      combination of intravenous immunoglobulin, granulocyte colony stimulating factor,
      conversion of calcineurin inhibitor and steroid pulse. The trigger of HPS may not
      only be systemic infection, but also hypercytokinemia caused by various factors.
      HPS is a fatal complication in immunologically compromised patients; however,
      early and accurate diagnosis could lead to an adequate treatment and improve the
      outcome.

PMID- 18613367
TI  - Successful re-transection of conglutinated hepatic resection plane for repeated
      systematized hepatectomy.
AB  - Although re-transection of a conglutinated hepatic resection plane is rarely
      necessary for repeated systematized hepatectomy, the operative procedure carries
      the risk of massive bleeding since it requires re-exposure of the main hepatic
      vein. We present a safe technique that allows successful re-transection of a
      tightly conglutinated resection plane. A 38-year-old man with liver metastasis of
      rectal cancer had undergone multiple repeated hepatic resections, including
      extended subsegmentectomy (segment 8), in which the middle hepatic vein was
      resected and the right hepatic vein was exposed on the resection plane of the
      right side. At presentation, the metastatic tumor located in segment 4 and the
      right hepatic vein was tightly conglutinated with the resection plane of segment
      4. Segmentectomy (Segment 4) with re-transection of conglutinated resection plane
      was necessary for both curability of tumor and preservation of remnant hepatic
      function. Resection of the remaining common channel of the left and middle
      hepatic vein allowed the tightly conglutinated resection plane to be safely
      resected from the left side, which was loosely conglutinated. Moreover, wide re
      exposure of the right hepatic vein from the root side allowed the control of any
      massive bleeding during this procedure. No blood transfusion was needed and the
      postoperative course was uneventful.

PMID- 18613368
TI  - Superior mesenteric venous thrombosis treated by direct aspiration thrombectomy.
AB  - A 69-year-old man, with hepatits C virus-related liver cirrhosis and hemophilia
      B, developed massive ascites and watery diarrhea after endoscopic injection
      sclerotherapy for esophageal varices. A multi detector row computed tomography
      revealed a superior mesenteric venous thrombus without bowel infarction. It was
      assumed that the thrombus was caused by transient congestion of the portal system
      after retrograde propagation of the sclerosant agent, in a condition where
      anticoagulation proteins, such as proteins C and S, had decreased. Because long
      systemic thrombolytic therapy was hazardous for the patient with hemorrhagic
      diathesis due to impaired coagulation, a direct thrombolysis was performed with
      urokinase followed by aspiration thrombectomy, with cannulation of the portal
      venous system using a transjugular intrahepatic approach. The patient had no
      complications in this procedure and subsequently diarrhea and refractory ascites
      were resolved. Direct thrombectomy via the transjugular intrahepatic route may be
      a useful therapy for mesenteric venous thrombus in the cirrhotic patient.

PMID- 18613369
TI  - Alcoholic diseases in hepato-gastroenterology: a point of view.
AB  - Alcohol damages every organ and system in the body. The most important effects
      from a clinical point of view relate to diseases of the circulatory, nervous and
      hepato-gastrointestinal systems. In the digestive tract the effects range from
      increased intestinal transit time and gastrophaties, leading to classical early
      morning nausea and diarrhea, through to significant malabsorption and chronic
      pancreatitis. In this review the mechanisms of alcoholic damage have been
      evaluated with particular reference to alcoholic liver disease (ALD). In
      particular, the natural history, the influence due to host genetic susceptibility
      and due to cofactors (i.e. hepatitis C virus), the clinical features and the
      hepatocarcinogenesis mechanisms have been evaluated. Finally, a possible role of
      abstinence in association with pharmacological therapy in the course of
      steatohepatitis has also been evaluated.

PMID- 18613370
TI  - Verification of evidence in surgical treatment for colorectal liver metastasis.
AB  - The liver is the predominant site of metastasis from colorectal carcinoma.
      Although surgical treatment has been widely clinically performed for colorectal
      liver metastasis (CLM), the evidence of its superiority to other non-surgical
      methods is unclear. Therefore, this review analyzed the evidence supporting
      surgical treatment for CLM. A MEDLINE search of papers published after 1990 was
      performed using the key words "colorectal liver metastasis" and "hepatectomy".
      Eligible papers were analyzed for evidence level, publication year, and study
      theme. One hundred and thirty-five papers were eligible for review. One hundred
      and twenty-one of 135 manuscripts showed evidence level 3 or 4. Only 3 papers
      showed level 1 (randomized controlled trial), all three of these were related to
      (neo-) adjuvant therapy. The numbers of manuscript have recently increased more
      than two-fold when the period investigated was divided into 5-year intervals.
      About one-third of papers were related to prognostic factors. Papers about
      surgical procedures, surgical results, diagnosis, and (neo-) adjuvant therapy
      follow after that in numerical order. In conclusion there is no strong evidence
      supporting the superiority of surgical treatment for CLM over other treatment
      methods.

PMID- 18613371
TI  - Risk and protective factors for development of colorectal polyps and cancer
      (Bulgarian experience).
AB  - BACKGROUND/AIMS: Colorectal cancer takes third place among all malignancies in
      the Varna region. The present study aims to determine the typical and
      distinguishing risk and protective factors for colorectal polyps and cancer
      formation. METHODOLOGY: 166 patients with large bowel polyps and 107 patients
      with colorectal cancer were questioned, examined endoscopically and
      histologically. Logistic regression analysis was used to find a possible
      correlation between alimentary habits, way of life, and risk for colorectal
      polyps and cancer formation. The latter have been used to define a strategy for
      their prevention. RESULTS: Our results showed that fried, preserved, and grilled
      meat, consumption of animal fats, sugar, and being overweight are positively
      associated with colorectal polyps. In contrast, consumption of fruit, vegetables,
      rye- and brown bread, green tea, vegetable food, yoghourt, vegetarian food, fish,
      lamb, hare, garlic, boiled food, and mineral water, have strong protective effect
      against large bowel polyps. We have confirmed the role of the well-known risk
      factors for colorectal cancer, and discovered an association between H. pylori
      infection, age, villous component in the adenomatous polyps, and family history
      for any neoplasia and large bowel carcinoma. CONCLUSIONS: We suggest the
      following protective factors for CRC: vegetarian food, plant oil, rural life,
      aspirin intake, legumes, fish, fruit and vegetable consumption. We observe a
      similarity between the risk factors for colorectal polyps and cancer formation.
      They act simultaneously and depend on genetic predisposition. A combination of
      endoscopic treatment and correction of the alimentary factors could be used as a
      means of cancer prevention.

PMID- 18613372
TI  - Cathepsin D and carcino-embryonic antigen in serum, urine and tissues of colon
      adenocarcinoma patients.
AB  - BACKGROUND/AIMS: Application of neoplastic markers in early diagnosis of
      colorectal carcinoma has brought fresh hope to millions of sufferers. However
      such a marker, distinctive for this particular carcinoma and allowing its
      detection at a sufficiently early stage of development has not yet been found.
      Cathepsin D (CD) is lysosomal aspartyl proteinase. It is a component of a
      proteolytic cascade participating actively in neoplastic invasion as well as in
      metastasis formation. Carcino-embryonic antigen (CEA) is a useful marker in
      oncological diagnostics of colorectal cancer. CEA undergoes expression in all
      kinds of adenocarcinoma and is found both intercellularly and extracellularly.
      High concentrations of CEA in the blood serum confirm neoplastic changes in the
      digestive tract with high probability. The objective of this study has been to
      evaluate CD activity in the blood serum, urine and tumor tissues as well as in
      the colon biopsies which were not changed macroscopically and CEA concentration
      in the serum of colon adenocarcinoma, considering the extent of spread of cancer
      (TNM), the grade of the differentiation of cancer cell (G) as well as the tumor
      size. The possibility of application of CD along with CEA as markers of colon
      adenocarcinoma has also been examined. METHODOLOGY: The examination included the
      serum and urine of 21 patients as well as 12 tissues biopsies with
      histopathologically confirmed colon adenocarcinoma. The reference group for the
      blood and urine comprised of 17 healthy controls, and for the colon
      adenocarcinoma tissues- samples collected from 14 people from the sites most
      distant from the resected tumor on the boundaries which were free of cancer
      cells. Activity of CD in the blood serum, urine as well as tissues was determined
      with a modified Greczaniuk et al. method and expressed by the amount of released
      tyrosine as the concentration of the activity in nmolTyr/mL/6h, whereas the
      specific activity was expressed in nmol Tyr/mg of protein /6h. The specific
      activity of CD in the urine was expressed in nmol Tyr/mg of creatinine/6h. CEA
      concentration in the blood serum was determined by the immunoenzymatic method
      (MEIA) on Axym Abbot Analyzer and was expressed in ng/mL. The protein
      concentration was determined by the Lowry method, and the results were expressed
      in mg/mL. The creatinine concentration in the urine was determined by the Jaffe
      method (without deproteinization) and was expressed in mg/100mL. RESULTS: CD
      activity was increased in the blood serum (p < 0.0001) and tissues (p = 0.022) of
      colon adenocarcinoma patients in comparison to the reference group. CD specific
      activity (Tyr/mg of protein/6h) was significantly increased in serum but
      decreased in the urine (p < 0.0001) whereas the specific activity of CD (nmol
      Tyr/mg of creatinine/6h) was increased in the urine (p = 0.0001). CD specific
      activity has tendency to increase in colon adenocarcinoma tissues (p = 0.441) as
      compared to the reference group. By examining data in regard to TNM clinical
      histopathological classification, G and the tumor size, it could be concluded
      that CD activity in serum and urine in colon adenocarcinoma patients depends on
      progress of cancer in which CD activity increases with TNM. A statistically
      significant increase in CEA concentration was found in the serum of colon
      adenocarcinoma patients, which was almost threefold higher than the in reference
      group. No significant differences in CEA concentration were found depending on
      TNM, G and tumor size. CONCLUSIONS: The results of this study suggest that
      examination of CD activity and CEA concentration in serum, as well as CD activity
      in the urine, might be used in oncological diagnostics of colon adenocarcinoma.

PMID- 18613373
TI  - Nrf2 gene promoter polymorphism is associated with ulcerative colitis in a
      Japanese population.
AB  - BACKGROUND/AIMS: Transcription factor Nrf2 regulates the expression of
      detoxifying and antioxidant genes. Three promoter polymorphisms of this gene have
      been identified. This study attempted to clarify the relationship between Nrf2
      gene polymorphism and ulcerative colitis in a Japanese population. METHODOLOGY:
      The study was performed in 89 patients with ulcerative colitis (mean age: 40.2
      years, M:F = 47:42) and 141 healthy volunteers (mean age: 38.7 years, M:F =
      75:66). The PCR-SSCP method was employed to detect Nrf2 polymorphisms using DNA
      extracted from peripheral blood cells. RESULTS: Comparison of genotype frequency,
      -686*-684 A* G/A*G genotype was significantly lower in the UC group than those in
      the HC group (OR = 0.45, 95% CI:0.22-0.93, p = 0.029) and G*G carrier was higher
      in the UC group, especially in female subjects. Furthermore, -686*-684 G*G
      carrier was more closely associated with chronic continuous phenotype (OR = 2.57,
      95% CI:1.01-6.60, p = 0.043). On the other hand, no association between -650
      genotype and ulcerative colitis was found. CONCLUSIONS: The -686*-684 genotype of
      Nrf2 gene may be associated with the development of ulcerative colitis.

PMID- 18613374
TI  - Positron emission tomography for preoperative staging in patients with locally
      advanced or metastatic colorectal adenocarcinoma in lymph node metastasis.
AB  - BACKGROUND/AIMS: The impact of positron emission tomography was prospectively
      evaluated using 18 (F)-fluoro-deoxyglucose (FDG-PET) for the detection of lymph
      node (LN) metastasis in preoperative locally advanced colorectal adenocarcinoma,
      compared with computed tomography (CT) and pathologic findings. METHODOLOGY:
      Fifty-three patients who were suspected of LN involvement by CT were staged
      preoperatively for LN metastasis using FDG-PET and CT. Regional LNs were
      classified into 3 groups, N1, N2-3, and N4, according to the Japanese General
      Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and
      Anus (6th Edition). A comparison of pathologic findings with CT and FDG-PET
      findings was used to calculate sensitivity, specificity, and accuracy. RESULTS:
      The sensitivity, specificity and accuracy of CT/FDG-PET were 91.3%/52.2%,
      91.7%/75.0% and 65.9%/72.3%, respectively, for N1, 91.7%/75.0%, 72.2%/94.4% and
      77.1%/89.6%, respectively, for N2-3, and 100%/100%, 17.6%/100% and 41.7%/100%,
      respectively, for N4. The detection rate of the num ber of metastatic N1 LNs by
      CT was significantly higher than by FDG-PET, and not significantly in the N2-4
      area. LNs hidden by strong halation of the primary tumor were not detected by FDG
      PET. CONCLUSIONS: While FDG-PET is markedly more sensitive than CT for detection
      of N4 LN involve. ment, the number of metastatic LNs is difficult to determine.

PMID- 18613375
TI  - Importance of thymidine phosphorylase, dihydropyrimidine dehydrogenase and
      thymidylate synthase expression at the invasive front of T3 rectal cancer as
      prognostic factors.
AB  - BACKGROUND/AIMS: We evaluated a relationship between postoperative recurrence and
      thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and
      thymidylate synthase (TS) expression at the invasive front of T3 rectal cancer.
      METHODOLOGY: This study was conducted on 61 patients with T3 rectal cancer who
      underwent surgically curative resection between 1998 and 2002. Paraffin-embedded
      sections of these patients were immunostained for TP, DPD and TS. Relationship
      between expression level of the three factors and postoperative recurrence were
      evaluated. RESULTS: There was no relationship between expression of DPD or TS in
      the tumor cells and recurrences. Although no relationship was present between
      expression of TP in the stromal cells around the invasive front of the tumor and
      postoperative recurrences, there was a strong correlation between expression of
      TP in the invasive front of the tumor and postoperative recurrence. Moreover, by
      multivariate logistic regression analysis, TP expression in the tumor cells was
      the only independent contributory factor for postoperative recurrences (p =
      0.021) with an odds ratio of 8.27. CONCLUSIONS: TP expression at the invasive
      front of the tumor may be an important prognostic factor for T3 rectal cancer,
      and patients with such a condition may benefit from intensive chemotherapy.

PMID- 18613377
TI  - Surgical resection for colon cancer: laparoscopic assisted vs. open colectomy.
AB  - BACKGROUND/AIMS: Laparoscopic surgery has been considered for more than a decade
      for treatment of colorectal cancer. Although its benefits in term of
      postoperative comfort and parietal preservation are commonly accepted, its
      efficiency to achieve proper oncologic resection and to prevent tumor recurrence
      are still debated. The purpose of this retrospective study is to compare results
      of a minimally invasive laparoscopic approach to these of open surgery for
      treatment of colorectal cancer. METHODOLOGY: From January 1st 1999 to September
      30th 2004, 239 patients underwent colorectal cancer resections; 28 of these
      patients underwent surgery in an emergent context and were excluded from this
      study. Accurate follow-up was available for 165 of the 239 patients (69%). For
      the study, 165 patients were divided into 3 groups: 39 patients underwent a
      laparoscopically assisted surgery (L group), 120 patients underwent an open
      colectomy (O group) and 6 patients initially treated with a laparoscopic approach
      were converted to open colectomy (L/O group) (conversion rate: 8.8%). RESULTS:
      Sex ratio, mean age and A.S.A. score, as well as patients' past records were
      similar in the 3 groups. Histological staging was more often stages 3 and 4 in
      the O group (62.5%) comparing to the L group (41%) (p < 0.5). Mean operating time
      was slightly longerwhen a laparoscopically assisted approach was used. Overall
      early mortality rate of this study was 1.8%. Combined local and general overall
      morbidity rate was 36%. Overall incidence of anastomotic fistulae was 4% and
      reintervention rate during the early postoperative period was 8%. Postoperative
      ileus period was often longer for patients of the O group but without statistical
      significance. Mean duration of hospital stay was similar in the 3 groups. Data
      concerning surgical resection did not show any difference between groups. None of
      the patients experienced a metastatic skin settlement. Overall anastomotic
      stenosis rate was low (2%). The overall locoregional recurrence rate was 12%,
      without difference between the 3 groups. Forty-two percent of these recurrences
      were secondarily treated by curative surgery. Similar survival rates as well as
      oncological spreading frequencies were found. CONCLUSIONS: Results obtained when
      comparing minimal invasive laparoscopically assisted surgery to open procedure
      are similar and efficient.

PMID- 18613376
TI  - A phase I trial of CPT-11 and S-1 combination chemotherapy in patients with
      metastatic colorectal cancer.
AB  - BACKGROUND/AIMS: To establish a safe and practical chemotherapeutic regimen using
      CPT-11 in combination with an oral 5FU derivative S-1 for patients with
      metastatic colorectal cancer, a phase I clinical trial was conducted in an
      outpatient setting. METHODOLOGY: Nine patients with metastatic colorectal cancer
      were enrolled. S-1 was administered at approved doses of 80 mg/body/day to
      eligible patients with a body surface area (BSA) of less than 1.25m2, 100
      mg/body/day to those with a BSA of 1.25-1.5m2, and 120 mg/body/day to those with
      a BSA of more than 1.5m2, for 2 weeks followed by 1 week rest, comprising one
      treatment cycle of 3 weeks. CPT-11 was administered on day 8 of the S-1 cycle.
      The dose of CPT-11 was escalated from 60-120 mg/m2 by every 20 mg/m2 for every
      cohort consisting of at least 3 patients in order to define dose-limiting
      toxicity (DLT), maximal tolerated dose (MTD), and recommended dose (RD) in
      preparation for a phase II trial. RESULTS: In regard to the hematologic toxicity,
      a decrease of WBC to less than grade 2 was observed in 2 patients until the dose
      was escalated to 100 mg/m2 of CPT-11, which delayed the treatment for 1 week in 1
      patient. Regarding non-hematologic toxicity, fatigue and gastrointestinal
      toxicity, including anorexia and nausea/vomiting, at grades 1 and 2 were commonly
      observed throughout the dose levels. Diarrhea at grade 3 was observed at the 4th
      cycle of 100 mg/m2 CPT-11 in 2 of 3 patients, both of whom required
      hospitalization. All patients were able to complete more than 3 treatment cycles,
      and 1 patient at 80 mg/m2 of CPT-11 was able to receive 31 treatment cycles.
      Observed tumor responses included 1 partial response (PR), 2 moderate responses,
      4 stable diseases, and 2 progressive diseases. Serum CEA level decreased in 7 of
      the 9 patients enrolled. CONCLUSIONS: These results suggest that this treatment
      regimen using CPT-11 in combination with oral S-1 therapy is a safe regimen in an
      outpatient setting and effective for patients with metastatic colorectal cancer.
      The DLT is diarrhea at a MTD of 100 mg/m2 of CPT-11, and 80 mg/m2 CPT-11 is
      recommended for the next phase II trial.

PMID- 18613378
TI  - Prognostic significance of the serum thymidine phosphorylase levels in venous
      blood drainage specimens in patients with colorectal cancer.
AB  - BACKGROUND/AIMS: We investigated whether the serum Thymidine phosphorylase (TP)
      levels in venous blood drainage specimens were associated with the prognosis and
      risk of liver metastasis in patients with resectable colorectal cancer.
      METHODOLOGY: From 88 patients with colorectal cancer, specimens of venous blood
      drainage were obtained during operation. The serum TP levels were measured by a
      highly sensitive Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULTS:
      Subsequently, 88 patients were divided into two groups based on the levels of TP.
      The dividing line was determined to be 55ng/mL. The TP-high group (> 55ng/mL) had
      a significantly shorter overall survival than the TP-low group (< 55ng/mL). A
      multivariate analysis indicated that the serum TP level in venous blood drainage
      specimens to be a better prognostic factor independent of the traditional
      pathologic parameters. The serum TP levels of 3 patients with metachronous liver
      metastasis were high (> 55ng/mL). CONCLUSIONS: These findings suggest that the
      serum TP levels in venous blood drainage specimens reflect the prognosis of
      patients with colorectal cancer undergoing curative resection, particularly the
      risk of liver metastasis.

PMID- 18613379
TI  - International and inter-observer differences in macroscopic classification of
      superficial early colorectal cancer.
AB  - BACKGROUND/AIMS: The aim of this research is to investigate the international and
      intra-observer differences in the macroscopic classification of early colorectal
      cancer between Japan and China. METHODOLOGY: Color pictures of 9 cases of early
      colorectal cancer were distributed to 6 Japanese and 5 Chinese endoscopists.
      After reviewing the pictures, the doctors made their classificatory diagnoses
      independently and indicated their findings on which the diagnoses were based.
      RESULTS: There was some consistency in the classification of distinctly elevated
      lesions among all the Japanese and Chinese endoscopists. However, some elevated
      lesions classified as type II in Japan might be diagnosed as type I by Chinese
      endoscopists. For superficial lesions consisting of elevation plus central
      depression, IIa+IIc or IIc+IIa, were classified according to the ratio of
      elevation and depression. Although international difference is not significant,
      inter-observer differences still exist in classifying these lesions. In addition,
      the differences in laterally spreading tumor were mainly due to terminology.
      CONCLUSIONS: Japanese and Chinese doctors share a lot of similarities in the
      classification of flat elevated lesions; however, both international and inter
      observer differences still exist in the macroscopic classification for early CRC.

PMID- 18613380
TI  - Anorectal manometry in patients with chronic constipation: a single-center
      experience.
AB  - BACKGROUND/AIMS: Constipation is a common complaint, but its clinical
      presentation varies with each individual. The aim of this study was to evaluate
      anorectal physiology in a prospective group of patients with chronic
      constipation. METHODOLOGY: A total of 24 consecutive patients with constipation
      underwent solid-state anorectal manometry. Fifteen healthy controls were also
      studied. The anorectal parameters included resting and squeeze sphincter
      pressure, sensory thresholds in response to balloon distension, compliance of
      rectum, and rectoanal inhibitory reflex (RAIR). RESULTS: The rectal sensitivity
      for urge and pain did not differ between the groups, but the threshold volume for
      first sensation was higher in patients with constipation (p < 0.05). There was no
      group difference in the volume threshold for RAIR. However, the prevalence of
      impaired RAIR was higher in constipated patients. Anal pressure was lower in
      patients for maximal squeeze (p < 0.05). There was a positive correlation between
      the anal sphincter length and resting pressure in patients (r = 0.51, p = 0.03)
      and healthy controls (r = 0.72, p = 0.01). CONCLUSIONS: Constipated patients are
      characterized by impaired rectal sensitivity and decreased anal sphincter
      contractile pressure. Anorectal manometry is helpful for diagnosing anorectal
      dysfunction in patients with chronic constipation.

PMID- 18613381
TI  - POSSUM is an optimal system for predicting mortality due to colorectal
      perforation.
AB  - BACKGROUND/AIMS: The purpose of this study was to determine the most useful
      predictive scoring system for the postoperative mortality of patients with
      colorectal perforation using the Acute Physiological and Chronic Health
      Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and
      Physiological and Operative Severity Score for the enUmeration of Mortality
      (POSSUM). METHODOLOGY: First, the 3 scoring systems were applied to all patients,
      and the efficacy of these systems was compared between survivors and non
      survivors. Second, using receiver operating characteristic (ROC) curve analysis,
      optimal cut-off values were determined for each system and patients were divided
      into another two groups (high score group and low score group). Then statistical
      analyses were performed, respectively. RESULTS: All scoring systems gave
      significantly lower scores for survivors than for non-survivors. POSSUM was the
      most sensitive system for predicting operative mortality (POSSUM: sensitivity
      87.5%). Kaplan-Meier analysis and log rank test revealed that there were
      significant differences between the high score group and the low score group,
      except for APACHE II. Multivariate logistic regression analysis revealed that
      only POSSUM was an independent predictor (odds ratio, 0.858; 95% C.I.; 0.736
      1,000; p = 0.0498). CONCLUSIONS: POSSUM is an optimal predictor of mortality
      following emergency surgery for colorectal perforation.

PMID- 18613382
TI  - The role of prophylactic bilateral oophorectomy at the time of initial diagnosis
      of a unilateral ovarian metastasis in cases with colorectal adenocarcinoma.
AB  - BACKGROUND/AIMS: In cases with a macroscopic unilateral ovarian metastasis of
      colorectal adenocarcinoma, a clear therapeutic policy regarding a prophylactic
      bilateral oophorectomy is lacking. METHODOLOGY: Four cases of ovarian metastases
      of colorectal adenocarcinoma are presented. RESULTS: Case 1 is a 63-year-old with
      ascending colon carcinoma, Dukes' C, and right oophorectomy due to metachronous
      ovarian metastasis. Case 2 is a 28-year-old with transverse colon carcinoma,
      Dukes' D, and right oophorectomy due to synchronous ovarian metastasis. Case 3 is
      a 40-year-old with rectal carcinoma, Dukes' B, and right oophorectomy due to
      metachronous ovarian metastasis. Case 4 is a 32-year-old with rectal carcinoma,
      Dukes' D, and bilateral oophorectomy due to synchronous and metachronous ovarian
      metastases. Later, in cases 1 and 3, in which a unilateral ovary was preserved,
      ovarian metastases to the preserved ovary were found and caused severe clinical
      symptoms. However, by that time their general condition did not permit any
      additional laparotomy. CONCLUSIONS: Without other extensive metastases, if
      demonstrable diseases are found in a unilateral ovary, a prophylactic bilateral
      oophorectomy is recommended.

PMID- 18613383
TI  - Current evidence supporting indications for laparoscopic surgery in colorectal
      cancer.
AB  - BACKGROUND/AIMS: Laparoscopic surgery for colorectal cancer has been widely
      adopted in clinical practice. In this review, recent randomized controlled trials
      (RCTs) investigating laparoscopic surgery for colorectal cancer are analyzed and
      the current evidence is summarized to examine the validity of this approach.
      METHODOLOGY: We retrieved studies performed via a MEDLINE search to identify
      prospective RCTs on laparoscopic surgery for colorectal cancer after January
      2000. Eligible RCTs were analyzed using the following items: publication year;
      geographical area and country; study theme; and sample size. RESULTS: Forty RCTs
      were analyzed. Most RCTs were carried out in Europe and Asia. Laparoscopic
      surgery was shown to be, at least as effective as open surgery both in short-term
      and long-term outcomes and was demonstrated to be a minimally invasive surgery
      with less effect on homeostasis. Although bladder dysfunction was not, sexual
      dysfunction was more frequently found in the laparoscopic group in patients with
      either bulky or low rectal cancers. CONCLUSIONS: Recent RCTs would validate the
      application of laparoscopic or laparoscopy-assisted surgery for colorectal cancer
      not only in patients with early colorectal cancer but also in advanced colorectal
      cancer.

PMID- 18613384
TI  - Acid and bile reflux in erosive reflux disease, non-erosive reflux disease and
      Barrett's esophagus.
AB  - BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) may occur with acid, bile
      or in a mixed form. Endoscopic injury and mucosal metaplasia are a known sequlae
      to pathological GERD. The aim of the study was to determine the contribution of
      acid and duodenogastroesophageal reflux (DGER) to endoscopic severity in patients
      with GERD and Barrett's esophagus. METHODS: Ninety-one patients complaining of
      reflux symptoms were studied with upper gastrointestinal endoscopy and graded to
      non-erosive reflux disease (NERD), erosive reflux disease (ERD) and Barrett's
      esophagus (BE). Esophageal manometry and simultaneous ambulatory 24-h esophageal
      pH and bilirubin monitoring (Bilitec 2000) were done to all patients. RESULTS:
      Seventy one patients (78.0%) had ERD (Savary-Miller (grade I-III), 11 patients
      (12.1%) had NERD and 9 patients (9.9%) had BE suspected endoscopically and
      diagnosed by histological esophageal biopsy. Combined 24-h esophageal bilirubin
      and pH monitoring revealed that 39 patients (42.9%) had mixed acid and bile
      reflux, 16 (17.6%) had pathological acid reflux only, 18 (19.8%) had bile reflux
      only and 18 patients (19.8%) had no evidence of abnormal reflux. The percentage
      of the total time of bilirubin absorbance above 0.14, in 71 patients with ERD was
      (8.18 +/- 11.28%), and in 9 patients with BE was (15.48 +/- 30.48%) which was
      significantly greater than that in 11 patients with NERD (4.48 +/- 8.99%), p <
      0.05 and p = 0.01 respectively. All BE patients had abnormal esophageal bile
      reflux (3 bile alone and 6 mixed bile and acid); 44 of 71 patients (61.97%) with
      ERD had abnormal esophageal bile reflux (13 bile alone and 31 mixed bile and
      acid); meanwhile 15 of them (21.2%) had abnormal acid exposure alone. Of the 11
      patients with NERD, 4 patients (36.4%) had abnormal esophageal bile reflux, 2 of
      them mixed with acid. CONCLUSIONS: The Bilitec method reliably identifies the
      presence of bilirubin and quantitatively detects duodenogastroesophageal reflux
      of bile. Mixed reflux (acid and bile) is the chief pattern of reflux in GERD
      patients in this study. Bile reflux either alone or mixed with acid reflux
      contributes to the severity of erosive and non-erosive reflux disease as well as
      to Barrett's esophagus.

PMID- 18613385
TI  - Open, randomized, comparative study of efficacy and safety between Haemopressin
      and Glypressin in treating acute esophageal varices hemorrhage.
AB  - BACKGROUND/AIMS: Hemorrhage from esophageal varices is a major consequence of
      liver cirrhosis. Pharmacological treatment can be started immediately by an
      internist to arrest acute esophageal variceal hemorrhage (EVH). Terlipressin is
      easy to administer and effective in treating acute EVH, with or without adjuvant
      endoscopic sclerotherapy, and in reducing mortality in these patients. Due to
      these potentials, a phase IV bioequivalence study was conducted to compare a new
      brand of terlipressin (Haemopressin: contains 1 mg tri-glycyl-lysin-vasopressin
      acetate) with one that is currently available in the market (Glypressin).
      METHODOLOGY: All cirrhotic patients with acute EVH were randomized to receive
      Haemopressin (n = 19) or Glypressin (n = 22) 2mg i.v. immediately followed by 1
      mg. i.v. q4h for 5 days. RESULTS: The demographics were similar between H-group
      and G-group. Successful control of acute bleeding within 24 hours was no
      different between the 2 groups (18/19 vs. 19/22). Failure to control bleeding
      within 5 days of drug administration was also no different between the 2 groups
      (4/19 vs. 6/22). Rebleeding events, the requirement for blood transfusions and
      rescued treatment were also comparative between the 2 groups. Half of the
      patients in either group had mild, temporary and self-limited side effects.
      CONCLUSIONS: The study confirms that administration of terlipressin, by either
      Haemopressin or Glypressin, is generally safe and indeed highly effective in the
      treatment of acute EVH.

PMID- 18613386
TI  - Esophagectomy in patients aged over 80 years with esophageal cancer.
AB  - BACKGROUND/AIMS: Esophagectomy for esophageal cancer is one of the most invasive
      surgical procedures. However, with the recent aging of the population, clinicians
      are increasingly encountering patients with advanced age (over 80 years) who
      require treatment for esophageal cancer. Patients in this age group tend to be
      regarded as at high risk in terms of surgical treatment. In the present study,
      the authors examined perioperative complications and clinical outcome in
      esophagectomy in patients aged over 80 years compared with those aged 70-79 and
      discuss the risk and appropriateness of esophagectomy in the older group.
      METHODOLOGY: Of patients with esophageal cancer at our institute, 25 were aged
      over 80 years, while 95 were aged 70-79 years. We statistically compared those
      who underwent esophagectomy; 8 in the older group and 62 in the younger group.
      The oldest patient was an 84-year-old man. Among the 8 older patients, 7 were
      male and 1 was female. All cases were histologically confirmed as squamous cell
      carcinoma and this series included 1 case in Stage 0, 3 in Stage I and 4 in Stage
      III. Total thoracic esophagectomy was performed in 5 patients, transhiatal blunt
      dissection in 2 and lower thoracic esophagectomy in 1. RESULTS: Rate of surgical
      treatment was significantly lower in the older group than in the younger group
      (32.0% vs. 65.3%, p < 0.001). No significant difference was observed in
      postoperative complications or mortality. Regarding clinical postoperative
      outcome in the older group, there were 5 deaths: 1 related to surgery, 2 to other
      causes (at 5 and 12 months), 2 to cancer (4 and 11 months). The remaining
      patients were alive at 31, 60, and 88 months. No significant difference was
      observed in overall or disease specific survival after surgery between the 2
      groups. CONCLUSION: No statistically significant differences were apparent in
      morbidity, mortality or clinical outcome in the 2 groups. Since surgery seems to
      confer similar symptomatic improvements and survival in patients aged over 80 to
      those expected for patients aged 70-79, we believe that surgeons should not
      withhold esophagectomy in patients aged over 80 years because of advanced age
      alone.

PMID- 18613387
TI  - Diagnosis and treatment of metachronous gastric cancers after surgical treatment
      for esophageal squamous cell carcinoma.
AB  - BACKGROUND/AIMS: With the improvement of the outcome after esophagectomy for
      esophageal cancer, patients with metachronous gastric cancer (MGC) in the
      reconstructed thoracic stomach have been observed in clinical practice. This
      study is a report of experiences with MGC with an emphasis on clinical pictures
      and treatment results. METHODOLOGY: Medical records were reviewed of 728 patients
      who underwent surgery for esophageal cancer at Samsung Medical Center between
      1994 and 2004. MGC was defined as follows; (1) diagnosed more than 6 months after
      esophagectomy, (2) squamous cell carcinoma in histology of the surgically
      resected esophagus, (3) adenocarcinoma in histology of the stomach biopsy or
      surgical specimen. The clinicopathologic characteristics of MGC were evaluated.
      RESULTS: Eight patients (1.1%) of 728 patients were diagnosed with MGC. All
      patients were male and had a history of active smoking and drinking. The median
      age at the time of diagnosis of MGC was 67.8 years old (range: 62-76). Three
      patients (37.5%) were asymptomatic. Two patients (25%) complained of epigastric
      pain and 3 patients (37.5%) complained of obstructive symptoms including
      regurgitation, aspiration, dysphagia, and vomiting. The median interval between
      diagnosis of MGC and esophagectomy was 37 months (range: 8-85). Three MGCs
      (37.5%) were detected by endoscopic examination but not by computed tomography
      (CT). Three patients (37.5%) received surgery and were alive without recurrence
      for 12, 18 and 63 months respectively. One patient (12.5%) received radiation
      therapy and was alive for 69 months. Four patients (50%) received no treatment
      because of follow-up loss in 2 patients (25%) and death within days of MGC
      diagnosis in 2 patients (25%). CONCLUSIONS: Favorable outcomes can be obtained by
      active treatment in patients with MGC after esophagectomy. Regular endoscopic
      follow-up is important for early detection and more effective treatment of MGC,
      especially in areas where the incidence of gastric cancer is high.

PMID- 18613388
TI  - Changes in small intestine permeability after radiotherapy of malignant tumor.
AB  - BACKGROUND/AIMS: Radiotherapy of the malignancy in the small pelvis causes
      different adverse events in normal tissues. The small intestine is the most
      sensitive organ in this region. Its wall performs the barrier function between
      internal and external environments. The damage to the intestinal barrier brings
      increase in the intestinal permeability. The aim of this study was to find out
      dependency of intestinal permeability disorder on certain factors such as age,
      radiation dose, target volume, dose per fraction, added chemotherapy etc.
      METHODOLOGY: We evaluated the intestinal permeability by the LAMA (lactulose
      mannitol) test in a group of 31 patients with a diagnosis of malignant
      gynecological tumor (24), rectal cancer (6) and prostate cancer (1) who underwent
      radiotherapy of the small pelvis with doses of at lest 45.0Gy. Fourteen patients
      underwent adjuvant radiotherapy, and 17 patients underwent a primary radical
      radiotherapy. In the latter group there was a tumor at the time of radiotherapy.
      The measurement was performed 3x (before starting radiotherapy, after its
      completion, and 6 months after completion). Complications after radiotherapy were
      assessed according to RTOG classification. LAMA test resultswere statistically
      worked out. RESULTS: Early complications G1, G2 were observed in 22 patients,
      late complications G1 in 3 patients. No dependency has been proved between grade
      of complications and intestine permeability changes. No evidence has been found
      in dependency on the patients' age, target volume, added chemotherapy, size of
      fraction, energy of radiation or other factors either. Connection of intestine
      permeability changes and total dose was on the margin of statistical
      significance; the only statistically significant relation was between intestinal
      permeability change and presence of tumor in the organism which was very
      surprising and cannot yet be explained. CONCLUSIONS: More patients should be
      involved in the study and late postirradiation changes should be assessed at a
      longer time interval.

PMID- 18613389
TI  - Patterns of traditional Chinese medicine use in patients with inflammatory bowel
      disease: a population study in Taiwan.
AB  - BACKGROUND/AIMS: Many researchers have reported on the utilization of
      complementary and alternative medicine by patients with inflammatory bowel
      disease (IBD). The aim of this study was to investigate the use of traditional
      Chinese medicine (TCM) by all IBD patients within the National Health Insurance
      in Taiwan. METHODOLOGY: The complete ambulatory visits records of TCM in 2004
      were obtained from the National Health Insurance Research Database. For all IBD
      patients identified from the registry for catastrophic illness patients, patterns
      of TCM visits were analyzed. RESULTS: The prevalence of IBD in Taiwan was 5.6 per
      100,000 persons at the end of 2004. Of 1,206 IBD patients, 440 (37%) patients
      have in total 3,169 TCM visits in 2004. Women were more likely to use TCM than
      men (40.5% vs. 34.3%). Among the TCM users of the IBD patients, 200 (45.5%)
      patients had gastroenterological diagnoses at their TCM visits. Most of their TCM
      visits contained herbal remedies (90%), followed by manual therapy (11.7%) and
      acupuncture (9.8%). CONCLUSIONS: The high utilization rate of TCM among the IBD
      patients in Taiwan implied that their needs of medical care were not satisfied by
      the mainstream Western medicine. The TCM herbal regimens deserve further studies.

PMID- 18613390
TI  - What is the prognostic significance of metastatic lymph nodes in GIST?
AB  - BACKGROUND/AIMS: So many variables have been identified as prognostic factors
      influencing survival after curative resection in gastrointestinal stromal tumors
      (GIST), but the role of lymph node metastasis remains uncertain. METHODOLOGY:
      Twenty-nine patients with c-Kit positive gastric GIST who underwent surgical
      resection at the Brazilian National Cancer Institute between 1983 and 2004 were
      reviewed retrospectively. The prognostic significance of lymph node metastasis
      was investigated. The endpoints were overall survival and disease free survival.
      RESULTS: The median follow-up was 35 months. The 5-years estimate survival rate
      was 53%. Three patients presented lymph node metastasis and developed recurrence
      disease. Univariate analysis for overall survival identified the size >13.5cm (p
      = 0.01) and recurrence (p = 0.03) as prognostic factors. Size > 13.5cm and
      recurrence were independent factors (p = 0.01 and p = 0.03, respectively) in the
      multivariate analysis. Univariate analysis for disease free survival identified
      the size > 13.5cm (p = 0.04) and the grade (p = 0.04) as prognostic factors but,
      only the size > 13.5cm was an independent factor in the multivariate analysis.
      Lymph node metastasis had no prognostic significance for overall and disease free
      survival (p = 0.65 and p = 0.57, respectively). CONCLUSIONS: GIST lymph node
      metastasis was not related to poor survival in this study, but more studies are
      needed to identify the real incidence and the proper role of the GIST metastatic
      nodal disease.

PMID- 18613391
TI  - Treatment results of adenocarcinoma of the gastroesophageal junction.
AB  - BACKGROUND/AIMS: In the treatment of cardiac cancer, the selection of surgical
      procedures is controversial. METHODOLOGY: In this study 297 resectable
      adenocarcinomas arising around the GE junction, that had their center within 5cm
      oral and aboral of the anatomical GE junction, were analyzed. They were
      subdivided into those with the tumor center located more than 1cm above the GE
      junction (Type 1, N = 7), those with the tumor center located within 1cm oral and
      2cm aboral of the GE junction (Type 2) and those with the tumor center 2cm below
      the junction (Type 3). Type 2 and 3 are subdivided into four groups as Type 2A (N
      = 47), 2B (N = 18), 3A (N = 37) and 3B (N = 188). Type 2A and 3A have esophageal
      invasion and Type 2B and 3B have no esophageal invasion. Thoraco-abdominal
      approach and transhiatal resection were done in 65 and 35 patients. Left and
      right thoracotomies were performed in 60 and 5 patients, respectively. RESULTS:
      Esophageal invasion distance of 83 among 84 Type 2A and 3A tumors limited within
      5cm from the GE junction. The maximum esophageal length by transhiatal approach
      was 6cm. Postoperative mortality rates after transhiatal approach and thoracotomy
      were 0% and 5.8%, respectively. One patient of Type 2A with No110 involvement
      survived longer than 5 years. No patients with Type 2A and 3A had recurrence in
      the upper mediastinal nodes after transhiatal approach and left thoracotomy.
      Mediastinal node involvement was found in 3 of 7 Type 1 tumors. Cox regression
      analyses revealed that the esophageal invasion distance (< 3cm vs. > 3cm), lymph
      node status (N0 vs. N2) and extent of lymph node dissection (D1 vs. D2) are the
      independent prognostic factors. CONCLUSION: Dissection of the lower thoracic
      paraesophageal nodes is recommended if the esophageal invasion longer than 1cm.
      Almost all Type 2A and 3A tumors can be treated by transhiatal approach without
      positive esophageal margin under a routine use of intraoperative frozen section.
      Right thoracotomy and the dissection of the upper mediastinal nodes are
      recommended for Type 1 tumor. Cardiac resection with D2 dissection is indicated
      for Type 1 and T1 tumors of Type 2. Total gastrectomy +D2 dissection is
      recommended for T2-3 tumors of Type 2 and T1-4 tumors of Type 3. Treatment should
      be selected according to the proposed classification.

PMID- 18613392
TI  - Interleukin 8 and 1beta and RANTES levels in esophageal mucosa predict recurrence
      of endoscopy-negative gastroesophageal reflux disease.
AB  - BACKGROUND/AIMS: Endoscopy-negative gastroesophageal reflux disease (ENRD), an
      incipient GERD phenotype without mucosal breaks, is a chronic relapsing condition
      with an impact on quality of life. Proinflammatory cytokines and chemokines play
      a role in the pathogenesis of various conditions including GERD. METHODOLOGY:
      This study investigated the relationship between interleukin 8 (IL-8), monocyte
      chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell
      expressed and presumably secreted (RANTES) and IL-1beta levels in esophageal
      mucosa and recurrence of the reflux symptom in 22 patients with ENRD. RESULTS:
      Based on analysis using Cox's proportional hazard regression model, significantly
      positive association was observed between the mucosal levels of cytokines (IL-8
      and -1beta and RANTES) and ENRD recurrence. Otherwise, parameters including age,
      gender, body mass index, smoking habits, alcohol intake, hiatal hernia and
      Helicobacter pylori status were not significantly related to relapse of the
      symptom. CONCLUSIONS: Enhanced production of such cytokines as IL-8 and -1beta
      and RANTES in esophageal mucosa can be potential predictors for ENRD recurrence.

PMID- 18613393
TI  - Serum pepsinogens as an early diagnostic marker of H. pylori eradication.
AB  - BACKGROUND/AIMS: Helicobacter pylori (H. pylori) eradication increases the serum
      pepsinogen I/ pepsinogen II ratio and the percentage change in pepsinogen
      I/pepsinogen II ratios is a useful marker of H. pylori eradication. We studied
      whether the pepsinogen method could be an early diagnostic marker of H. pylori
      eradication even in patients persistently treated with a proton pump inhibitor.
      METHODOLOGY: Sixty-two H. pylori-positive patients underwent H. pylori
      eradication therapy, followed by treatment with a proton pump inhibitor to cure
      ulcers. Serum levels of pepsinogen I and pepsinogen II were measured before, at
      the end of, and at 4 weeks after the eradication therapy. The cut-off values of
      percentage changes in pepsinogen I/pepsinogen II ratios for the diagnosis of
      eradication of H. pylori were set in proportion to pepsinogen I/pepsinogen II
      ratios before eradication in accordance with a previous report. RESULTS: Using
      the results of 13C-urea breath test as the standard, the sensitivity, specificity
      and validity of the pepsinogen method were 100.0%, 89.8% and 90.3%, respectively,
      at 4 weeks after eradication therapy. CONCLUSION: The percentage change in serum
      pepsinogen I/pepsinogen II ratios is useful as an early diagnostic marker for
      judgment of H. pylori eradication irrespective of proton pump inhibitor
      treatment.

PMID- 18613394
TI  - Effect of hyperbaric oxygen therapy on patients with adhesive intestinal
      obstruction associated with abdominal surgery who have failed to respond to more
      than 7 days of conservative treatment.
AB  - BACKGROUND/AIMS: To investigate the effects of hyperbaric oxygen (HBO) therapy on
      patients with adhesive intestinal obstruction who have failed to respond to more
      than 7 days of conservative treatment. METHODOLOGY: Six hundred eighty-five
      patients, who were admitted a total of 879 times for adhesive intestinal
      obstruction, were divided into groups according to the treatment and interval
      between the first day of the therapy and clinical symptoms of obstruction; tube
      decompression therapy within 7 days after appearance of clinical symptoms (Group
      I: n = 321), clinical symptoms that have persisted for less than 7 days before
      the start of HBO therapy (Group II: n = 498), and for more than 7 days (Group
      III: n = 60). RESULTS: The overall resolution and mortality rates in the cases of
      adhesive intestinal obstruction were 79.8% and 2.2% in Group I, 85.9% and 1.4% in
      Group II, and 81.7% and 1.6% in Group III, respectively. Group II had
      significantly better resolution rates than Group I (odds ratio 1.6, p < 0.02).
      CONCLUSIONS: HBO therapy may be useful in management of adhesive intestinal
      obstruction associated with abdominal surgery, even in patients who fail to
      respond to other conservative treatments. HBO therapy may be a preferred option
      for treatment of patients for whom surgery should be avoided.

PMID- 18613395
TI  - Factors influencing the development of small intestinal obstruction following
      gastrectomy for early gastric cancer.
AB  - BACKGROUND/AIMS: The factors influencing the development of small intestinal
      obstruction following gastrectomy for early gastric cancer are controversial.
      METHODOLOGY: Univariate and multivariate analyses were carried out using data
      from 136 patients with early gastric cancer who underwent gastrectomy. The mean
      follow-up interval was 5 years and 11 months. RESULTS: Of these 136 patients,
      15(11.0%) presented mechanical obstruction in the small intestine
      postoperatively. Re-operation for repair of the related ileus was required in 8
      patients, 4 of whom had been treated with total gastrectomy, 7 with resection of
      the greater omentum, and 3 with concomitant resection of other organs.
      Development of an obstruction was not related to wide resectional procedures such
      as extended lymph node dissection or combined resection of other organs, but was
      significantly correlated with total gastrectomy and resection of the greater
      omentum (p < 0.05). In multivariate logistic regression analysis, total
      gastrectomy proved to be a significant risk factor related to the development of
      small intestinal obstruction. CONCLUSIONS: In patients with early gastric cancer,
      total gastrectomy should not be attempted to prevent postoperative ileus and to
      ensure a fairly sustained quality of life.

PMID- 18613396
TI  - Regulation of the peptidergic nerves (substance P and vasoactive intestinal
      peptide) in the colon of women patients with slow transit constipation: an in
      vitro study.
AB  - BACKGROUND/AIMS: In histological studies, there is evidence to suggest a
      diminution of the peptidergic nerves such as vasoactive intestinal peptide (VIP)
      and substance P (SP) in the enteric nervous system in the colon of patients with
      slow transit constipation (STC). To clarify the pathophysiological significance
      of peptidergic nerves in the colon of patients with STC, we investigated the
      enteric nerve responses on pathological and normal bowel segments derived from
      patients with STC and patients who underwent colon resection for colon cancers,
      respectively. METHODOLOGY: Twenty-eight preparations were taken from the
      pathological sigmoid colon of 16 women with STC (aged 40-58 years, average 48.8
      years). Forty-eight preparations were taken from the normal sigmoid colon of 20
      women with colonic cancer (aged 40-55 years, average 49.6 years). A
      mechanographic technique was used to evaluate in vitro muscle responses to VIP
      and SP of adrenergic and cholinergic nerves before and after treatment with
      various autonomic nerve blockers. RESULTS: Responses mediated by non-adrenergic
      non-cholinergic (NANC) inhibitory nerves were found in the normal colon, but were
      more frequently in the colon with STC than in the normal colon (p < 0.01).
      Responses mediated by excitatory nerves such as cholinergic nerves were more
      dominant in the normal colon than in the STC colon. At 1 x 10(-8), 1 x 10(-7), 1
      x 10(-6) g/mL, VIP and SP in both the normal and STC colonic muscle strips
      produced a concentration-dependent relaxation to VIP and contraction to SP. In
      addition, the relaxation reaction to VIP in the colon with STC was also weaker
      than in the normal colon (p < 0.01). The contraction reaction to SP in the colon
      with STC was weaker than in the normal colon (p < 0.01). VIP acts through neural
      mechanisms, whereas SP may act both through nerves and also directly on both the
      normal and STC muscle strips. CONCLUSIONS: Responses mediated by NANC inhibitory
      nerves were significantly increased in the colon with STC compared with the
      normal colon. A decrease of responses to peptidergic nerves such as SP and VIP
      may also play an important role in the impaired motility observed in the colon of
      patients with STC. These results indicate that the disturbances in the neural
      component of the enteric nervous system in the colon of women patients with STC
      may initiate or contribute to the functional changes.

PMID- 18613397
TI  - Expression of 8-hydroxydeoxyguanosine in the gastric remnant after distal
      gastrectomy.
AB  - BACKGROUND/AIMS: The correlation between remnant gastritis after distal
      gastrectomy for gastric cancer and expression of 8-hydroxydeoxyguanosine (8-OHdG)
      and inducible oxide synthase (iNOS) as a marker of oxidative DNA damage was
      investigated. METHODOLOGY: Ninety-seven patients who had undergone curative
      distal gastrectomy for gastric cancer were studied. Reconstructive procedures
      included Billroth I, Billroth II, and Roux-Y reconstruction in 42, 27, and 28
      patients, respectively. Histologic and immunohistochemical analyses were
      performed on biopsy specimens of the gastric mucosa obtained endoscopically
      within 2 weeks before and 12 weeks after surgery. The grades of remnant gastritis
      were evaluated according to the updated Sydney System. 8-OHdG and iNOS expression
      levels, detected immunohistochemically, were graded. RESULTS: Neutrophil
      infiltration correlated with expression of 8-OHdG (p = 0.02). Expression of iNOS
      also correlated with 8-OHdG (p = 0.02). The ratio of postoperative to
      preoperative infiltration of neutrophils was less in patients who underwent Roux
      Y reconstruction than in others (p = 0.04). CONCLUSIONS: These results suggest
      that remnant gastritis possibly causes DNA damage. Excess production of reactive
      oxygen species correlates with carcinogenic DNA changes. Roux-Y reconstruction
      may reduce carcinogenesis in the gastric remnant.

PMID- 18613398
TI  - Surgical treatment for gastric GIST with special reference to liver metastases.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumor (GIST) is recently defined as a
      tumor expressing c-kit and sometimes showing liver metastasis. We investigated
      the outcomes of gastric GIST with special attention to the effect of repeated
      treatment for the patients with liver metastases. METHODOLOGY: Fourteen gastric
      GISTs were retrospectively reviewed and the significance of the NIH
      stratification system was examined. RESULTS: Liver metastasis was found in 4 of
      the 14 patients with gastric GISTs. Three of the 4 patients had metachronous
      liver metastases and underwent repeated hepatectomies after the initial operation
      for gastric GIST. The other patient had a synchronous liver metastasis and
      underwent total gastrectomy and partial resection of the liver as the initial
      treatment. Two of the 4 patients have received treatments 6 times, including
      hepatic resection, microwave coagulation therapy (MCT), radiofrequency ablation
      (RFA), or by imatinib. All 4 patients with hepatic metastases are alive after the
      first hepatectomy with a mean survival time of 64.8 months with or without
      imatinib treatment. None classified to very low risk and low risk groups by the
      NIH system showed liver metastasis, while 43% of the patients classified to the
      high risk showed liver metastasis. CONCLUSIONS: Repeated surgical and medical
      treatments for liver metastases from gastric GIST improve survival. Special
      attention should be paid to be the high risk group categorized by the NIH
      classification system.

PMID- 18613399
TI  - Safety and long-term outcome of a new concept for surgical adhesion-reduction
      strategies (Prevadh): a prospective, multicenter study.
AB  - BACKGROUND/AIMS: No agent has been consistently effective in preventing formation
      of peritoneal adhesions and postoperative bowel obstruction after abdominal
      surgery. The aim of this prospective multicenter study was to assess clinical
      safety and efficiency of a new adhesion-reduction barrier METHODOLOGY: Between
      September 2000 and April 2001, Prevadh was used in 78 patients. Operative
      procedures included 25 hepatic resections, 7 cholecystectomies, 32 colonic
      resections, 7 protectomies, 3 colostomy or recovery of continuity, 1 gynaecologic
      surgery and 3 others. Eleven patients were operated on by laparoscopy and 67 by
      laparotomy. RESULTS: The overall incidence of abscesses and wound complications
      was 2.4% and 9% respectively. After a mean follow-up of 36 months (range: 4-51
      months), no patients experienced adverse events related to the adhesion barrier.
      Surgical reoperative procedures were performed in 10 patients for unrelated
      causes and no bowel obstruction occurred within the protected area. CONCLUSIONS:
      This study confirmed the safety of Prevadh adhesion barrier and suggested that
      this resorbable barrier might provide prevention from adhesion formation on
      peritoneal injured surfaces. However, a large randomized controlled trial remains
      necessary to prove the real effectiveness of adhesion barriers on clinical long
      term outcome.

PMID- 18613400
TI  - Laparoscopic management of acute small bowel obstruction: a retrospective study
      on 156 patients.
AB  - BACKGROUND/AIMS: Laparoscopic treatment of small bowel obstruction (SBO) has been
      proposed in selected patients. This study reports an experience and tries to
      establish indications for laparoscopy. METHODOLOGY: 156 patients underwent
      laparoscopic or open approach for SBO. Demographics, clinical, biological,
      radiological and previous surgery were recorded. Obstruction causes, conversion
      rates and postoperative complications were retrospectively analyzed. RESULTS:
      Laparoscopic approach was undertaken for 96 patients (61%) and completed in 62
      (65%), whereas 34 (35%) required conversion. 60 patients (39%) underwent a direct
      open approach. Mortality was 10% and morbidity 38%. Postoperative adhesion was
      the predominant etiology. Conversion rate and type of approach was directly
      influenced by cause of obstruction and type of previous surgery, but not by
      number of previous surgeries. Conversions and open approach increase morbidity,
      mortality, length of stay and return to transit. CONCLUSIONS: Laparoscopy is an
      elegant tool for management of selected patients with SBO. A single band of
      obstruction appearing after minor surgery appears to be a good indication for
      laparoscopy. Nevertheless, conversion rate and morbidity are still high. On the
      contrary, laparoscopy seems contraindicated for patients with prior history of
      major abdominal surgery, neoplasia or multiple laparotomies, and a direct open
      approach is then advocated. Prospective randomized studies comparing laparoscopy
      and open approach are required to evaluate their respective efficacy and safety
      in management of SBO.

PMID- 18613401
TI  - Retroperitoneal "Triton" tumor.
AB  - Malignant Triton tumor is a malignant peripheral nerve sheat tumor with
      rhabdomioblastic differentiation. These tumors are frequently associated with
      Neurofibromatosis type 1, sporadic cases being exteremly rare. Retroperitoneal
      localization have the most unfavorable prognois due to delayed diagnosis but also
      due to relation to adjacant organs. Preoperative diagnosis is inaccurate, but
      core needle biopsy gives more promising results. Aggressive surgical management
      remains the most effective modality since adjuvant forms of treatment like
      irradiation or chemotherapy do not have reproducible results. We present a 60
      year-old female patient in whom a retroperitoneal presacral mass was
      postoperatively diagnosed as Triton tumor. At time of diagnosis, no visible
      metastases were present. The posterior pelvic exenteresis was performed. Intended
      chemotherapy was never started since multiple pulmonary, hepatic and splenic
      metastases were diagnosed only a month after surgery, with rapid lethal outcome.
      This case demonstrates the bad prognosis of malignant retroperitoneal tumors.
      Diagnostic tools such as refined biopsy techniques or cytogenetic analysis might
      help in differentiating patients who will benefit from radical surgery.

PMID- 18613402
TI  - Therapeutic effect of TAE can be predicted by abdominal-enhanced CT findings in
      HCC.
AB  - BACKGROUND/AIMS: In order to improve the therapeutic efficacy of transcatheter
      arterial embolization (TAE) in hepatocellular carcinoma (HCC), the relationship
      between CT findings and antitumor efficacy was studied. METHODOLOGY: The
      therapeutic effect on CT 1 year after TAE was respectively studied for 100
      nodules of HCC where TAE was performed. The pre-treatment abdominal CT findings
      were classified, and the therapeutic effect was compared with regard to these
      attributes. RESULTS: Tumors determined to have no recurrence at the treated site
      (defined as "complete necrosis") accounted for 58% overall. The percentage of
      "complete necrosis" in pre-TAE CT findings by type showed that 1) in terms of
      tumor shape, 73.4% were smooth type, 34.5% irregular type, and 0% invasive type
      (p = 0.0003), 2) in terms of the presence of corona nodules, nodules where
      "complete necrosis" was achieved were corona-positive in 67.7% and coronanegative
      in 37.1% (p = 0.003), 3) in terms of tumor size, 68.3% of tumors were smaller
      than 3.0cm and 28.6% were larger than 3.1cm, 4) in terms of location, 64.6% of
      tumors were in a peripheral location and 28.6% in a central location (p = 0.006).
      CONCLUSIONS: The therapeutic effect of TAE is improved by adequate diagnosis of
      the tumor characteristics found on pre-treatment CT.

PMID- 18613403
TI  - Matrix metalloproteinases 2 and 9 correlate with alanine aminotransferase and
      hepatitis C virus in blood donors.
AB  - BACKGROUND/AIMS: Matrix metalloproteinases 2 and 9 (MMP-2 and -9) have been
      suggested to play an important role in hepatitis and hepatic fibrosis. The aims
      of this study were to determine the plasma levels of enzyme activities of matrix
      metalloproteinases 2 and 9 in healthy and deferred blood donors. The
      relationships between activities of matrix metalloproteinases 2 and 9 and the
      level of alanine aminotransferase and the status of hepatitis B virus and
      hepatitis C virus infection were investigated. METHODOLOGY: This study included
      51 healthy volunteer blood donors and 175 deferred blood donors. Of the deferred
      donors, 54 donors had levels of alanine aminotransferase > or = 45 IU/L, 99
      donors were positive for hepatitis B virus surface antigen, and 32 donors were
      positive for antibodies against hepatitis C virus. Activities of matrix
      metalloproteinases 2 and 9 were measured by zymography using impregnated gel.
      RESULTS: Activity of matrix metalloproteinase 2 in deferred blood donors with
      elevated ALT was higher than that in healthy donors (331 +/- 139 vs. 266 +/- 122,
      p < 0.001). Further, activity of matrix metalloproteinase 2 was higher in HCV
      infected donors than in healthy donors (319 +/- 97 vs. 275 +/- 133, p < 0.05).
      Matrix metalloproteinase 9 activity was also higher in deferred donors with HCV
      infection than in healthy donors (153 +/- 45 vs. 108 +/- 48, p < 0.001).
      CONCLUSION: These findings suggest that hepatitis C virus infection may
      upregulate the activities of matrix metalloproteinases 2 and 9 and that these
      matrix metalloproteinases may be linked to liver dysfunction.

PMID- 18613404
TI  - Prognostic value of the monoethylglycinexylidide (MEGX)-test prior to liver
      resection.
AB  - BACKGROUND/AIMS: The critical issue before major hepatic resection is to evaluate
      and detect patients with a potentially increased risk of hepatic failure. In this
      study the prognostic value of the monoethylglycinexylidide (MEGX)- liver function
      test was evaluated with regards to clinical course and survival after partial
      liver resection. METHODOLOGY: Between 1995 and 2000 a total of 55 patients (29
      male, 26 female) underwent a partial liver resection at the Georg-August
      University of Gottingen. Forty-two patients were treated for malignant, and 13
      for benign, disease. MEGX-testing was performed 15 and 30 minutes after a single
      dose of 1mg/kg BW Lidocaine i.v. was applied. RESULTS: MEGX-test results after 30
      minutes had significant influence on hospital mortality. Patients who died during
      the hospital stay showed median MEGX-30 minutes results of 32 microg/L in (4-107
      microg/L) in comparison to the surviving patients with a median 68 microg/L (16
      176 microg/L) (p = 0.026). Furthermore, patients with MEGX scaled categories of 3
      and 4 had a significantly lower surivial at 150 days (p = 0.008) and overall (p =
      0.0002). There was an indirect impact of MEGX on hospital stay, costs and
      mortality reflecting high fluid loss: patients with lower loss of fluid over
      drainages had a significantly lower mortality at 150 days (p = 0.00046) and
      overall (p = 0.00008), than did patients with higher fluid loss. Low MEGX-values
      significantly influenced long hospital stay (p = 0.00001) and high costs (p =
      0.00001). Pathologic MEGX in combination with increased age, increased BMI and
      extensive surgical procedures including resection of over 50% volume of the liver
      had a significant influence on complications (p = 0.015). CONCLUSION: The
      preoperative MEGX-test, especially the 30 minutes value, is a useful medium to
      estimate the liver reserve in non-cirrhotic patients prior to liver resection. In
      combination with the resection volume it may be very useful to identify patients
      with a high risk of developing a postoperative liver failure.

PMID- 18613405
TI  - Clinical significance of serum HGF and c-Met expression in tumor tissue for
      evaluation of properties and treatment of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: To develop a prognostic marker for evaluation of intrahepatic
      metastasis (IM) of hepatocellular carcinoma (HCC), the ligand-stimulated receptor
      activity of c-Met due to hepatocyte growth factor (HGF) was estimated.
      METHODOLOGY: For specimens from 30 HCC patients, who were operated on at the
      Department of Surgical Oncology, Gifu University School of Medicine, for 2 recent
      years, the induction value of HGF and c-Met were estimated by western blot.
      RESULTS: Firstly, the serum HGF levels were significantly higher in invasive
      gross type or in IM-positive tumors. Secondly, the mean expression value of HGF
      protein in tumors was 0.56 +/- 0.35, which was not different from non-tumor
      tissue, 0.59 +/- 0.40. And there was no significant differences based on tumor
      profiles. Thirdly, the value of c-Met in tumor tissue, 1.36 +/- 0.12, was clearly
      higher than in non-tumor tissue, 1.07 +/- 0.06. The c-Met expressions were
      significantly higher in the invasive type of HCC as determined by gross type,
      vessel invasion, IM presence and histological type. Finally, in individual
      studies about the relationship between the level of serum HGF and c-Met
      expression in tumor tissue, the presence of IM could be easily detected.
      Furthermore, the level of serum HGF after hepatectomy was significantly higher
      than the preoperative value, and individual studies with c-Met expression were
      associated with early recurrence. CONCLUSIONS: The induction of c-Met might be
      important to evaluate the progression of HCC, especially to caution for the
      presence of IM.

PMID- 18613406
TI  - Intraoperative thermal ablation therapy for small colorectal metastases to the
      liver.
AB  - BACKGROUND/AIMS: Thermal ablation (TA) therapies such as microwave coagulation
      therapy (MCT) and radiofrequency interstitial thermal ablation (RFA) for
      colorectal metastasis to the liver cannot always achieve a complete tumor cell
      death, and the multiple insertions of the TA probe may lead to intrahepatic
      dissemination and/or distant metastasis. METHODOLOGY: The achieved local control
      rate, any recurrence in the residual liver, and any extrahepatic recurrence has
      been evaluated in 105 patients who underwent hepatectomy and/or intraoperative TA
      between 1994 and 2004. RESULTS: A total of 102 unresectable liver metastatic
      lesions (mean size 21mm) were selectively treated with TA either as initial
      treatment (32 patients) and/or as re-treatment (18 patients) for recurrence in
      the residual liver, in combination with hepatectomy. Overall, TA achieved a high
      local tumor control rate of 95%. Multivariate analysis revealed that initial-TA
      therapy was not a significant predictive factor of hepatic recurrence or any
      recurrence. CONCLUSION: TA therapies in combination with hepatectomy may offer
      increased resectability without increased risk of intrahepatic dissemination or
      extrahepatic recurrence for certain patients who would otherwise be deemed
      inoperable, when relatively small tumors are indicated for TA.

PMID- 18613407
TI  - State of the iron metabolism in patients with chronic hepatitis C type C does not
      influence antiviral treatment with interferon and ribavirin.
AB  - BACKGROUND/AIMS: Comparison of the iron status in patients who responded and did
      not respond to combination treatment with interferon alpha and ribavirin in
      chronic hepatitis C. METHODOLOGY: The study group comprised of 61 patients with
      chronic hepatitis C (genotype 1) treated with alpha 2b interferon and ribavirin.
      The iron metabolism was evaluated based on serum iron level, total iron binding
      capacity, transferrin saturation, serum ferritin concentration and hepatic iron
      concentration. In the evaluation of antiviral treatment efficacy biochemical and
      virological responses were taken into account. RESULTS: End of treatment response
      was observed in 38 patients (62%). Significant differences in iron parameters
      were not observed between responders and non-responders. Also, sustained viral
      response, 6 months after treatment completion, was reached in 32 patients
      (52.5%). Iron metabolism parameters did not differ significantly in the group of
      sustained responders versus non- responders. Finally, ALT normalization was
      observed in 42 patients (68.9%). Again, no significant differences in iron status
      were observed between patients with and without biochemical response excluding
      significantly higher serum ferritin concentration in non-responders. CONCLUSIONS:
      Results of this study show that iron status does not significantly influence the
      efficacy of treatment with interferon and ribavirin in patients with chronic
      hepatitis C.

PMID- 18613408
TI  - Use of radiofrequency ablation in the treatment of malignant liver lesions.
AB  - BACKGROUND/AIMS: The authors present their experience with the option of using
      radiofrequency ablation (RFA) in the treatment of malignant focal liver lesions.
      METHODOLOGY: In a prospective study conducted in the period from 2002-2005, 60
      patients were treated using RFA during a total of 72 sessions and treating 108
      lesions of various size, number and localisation. The method of RFA was applied
      either percutaneously under computed tomography (CT) or ultrasonographic (USG)
      navigation (22 patients) or surgically--during opened laparotomy or laparoscopy
      (42 patients). RESULTS: Median observation time was 12.7 months (with the range 3
      36 months). Authors did not observe any serious complications after RFA treatment
      in the study population. Median time of local recurrence in the ablated lesion
      position was 13.5 months in the observed population, median time of metastatic
      progression in the residual liver parenchyma was 12 months, and overall median
      survival was 22 months. Percutaneous RFA application demonstrated significantly
      worse results when compared with surgical application in previously the mentioned
      parameters. Lesions larger than 3cm in diameter also showed statistically more
      frequent local recurrence. CONCLUSIONS: RFA is appreciated as minimally invasive
      method of treatment for liver malignancies with promising perspectives of
      therapeutic effects.

PMID- 18613409
TI  - Urinary trypsin inhibitor improves viability of the liver in brain-dead rats.
AB  - BACKGROUND/AIMS: The present study examined the effect of urinary trypsin
      inhibitor (UTI) on liver injury in hypotensive brain-dead rats. METHODS: Brain
      death was induced by inflating a balloon catheter placed in the epidural space.
      UTI (100,000 units/kg/hour) was intravenously administered from 30 min until 6
      hours after the induction of brain death. Systemic hemodynamics and hepatic
      tissue flow (HTF) were measured, and blood samples and hepatic tissue specimens
      for morphological examinations were obtained during the experiments. RESULTS: The
      induction of brain death caused a 30% decrease in both mean arterial pressure and
      HTF, and an increase in the serum transaminase level in comparison with sham
      operated rats. Brain death also increased the serum concentration of cytokine
      induced neutrophil chemoattractant (CINC) (4.4-fold), as well as the number of
      CINC-positive cells (4.4-fold) and sequestered neutrophils in the sinusoids (3.1
      fold). Post-treatment of brain-dead rats with UTI restored the HTF and reduced
      serum transaminase level. UTI decreased plasma CINC level and the number of
      neutrophils and CINC-positive cells in the sinusoids. CONCLUSIONS: The results
      suggest that treatment with UTI after the establishment of brain death improved
      the viability of the liver in hypotensive brain-dead rats by inhibiting CINC
      production.

PMID- 18613410
TI  - Influence of Dai-kenchu-to (DKT) on human portal blood flow.
AB  - BACKGROUND/AIMS: Dai-kenchu-to (DKT) is known as an herbal medicine used for
      postoperative ileus. However, no report exists about the effect of DKT on portal
      blood flow. The aim of this study is to clarify the influence of DKT on portal
      blood flow. METHODOLOGY: To healthy volunteers (Healthy; n = 6), cirrhotic
      patients (Cirrhosis; n = 7) and liver-transplant patients (LTx; n = 3), DKT
      (2.5g) with 100mL of warm water was orally administrated in the DKT group, and
      only warm water was administrated in the control group. The portal blood flow
      rate (M-VEL: cm/sec.) and portal blood flow (Flow volume: mL/min.) was measured
      each time after administration using an ultrasonic Doppler method. Furthermore,
      the arterial blood pressure and heart rate was measured at the same time points.
      RESULTS: In the DKT group, a significant increase of M-VEL (120%) and flow volume
      (150%) 30 minutes after administration was observed in both Healthy and Cirrhosis
      in comparison with the control group. In LTx, there was also a significant
      increase of flow volume (128%) 30 minutes after administration. However, there
      was no change in average blood pressure and heart rate in all groups.
      CONCLUSIONS: DKT increases portal blood flow in early phase after oral
      administration without any significant changes in the blood pressure and heart
      rate.

PMID- 18613411
TI  - Factors associated with natural seroclearance of hepatitis B surface antigen and
      prognosis after seroclearance: a prospective follow-up study.
AB  - BACKGROUND/AIMS: Although the natural seroclearance rate of Hepatitis B surface
      antigen (HBsAg) is reported to be 0.4-2% in western countries, this is not well
      known in Korea. This study aimed to elucidate the rate of natural HbsAg
      seroclearance, factors associated with seroclearance and prognosis after
      seroclearance. METHODOLOGY: In 1999, 250 chronic HBsAg carriers without any
      history of antiviral treatment and without any evidence of liver cirrhosis or
      hepatocellular carcinoma were selected. Follow-up HBsAg/ anti-HBs tests were
      performed annually till 2004. During a mean follow-up period of 48 months, 24
      patients were lost and 11 received antiviral treatment. Finally, 215 patients
      completed the study. RESULTS: HBsAg seroclearance was observed in 11 patients (6
      males, 5 females). One-year seroclearance rate was 1.4%. All patients who
      achieved seroclearance were HBeAg (-)/HBV DNA (-) at the time of enrollment.
      Additionally, old age and normal serum alanine aminotransferase (ALT) level were
      the factors associated with seroclearance (p < 0.05, respectively). During the
      follow-up period, only mild transient elevations of ALT were observed in 4
      patients and no serious complications were observed. CONCLUSIONS: Natural
      seroclearance occurred exclusively in patients who were HBeAg (-)/HBV-DNA (-),
      and annual rate of natural HBsAg seroclearance was 1.4%. No significant
      complications were observed after seroclearance.

PMID- 18613412
TI  - Clinical role of FDG-PET for HCC: relationship of glucose metabolic indicator to
      Japan Integrated Staging (JIS) score.
AB  - BACKGROUND/AIMS: The purpose of this study was to validate the usefulness of
      positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) in
      predicting degree of malignancy and prognosis, evaluated in terms of Japan
      Integrated Staging (JIS) score, in cirrhotic patients with hepatocellular
      carcinoma (HCC). METHODOLOGY: FDG-PET was performed in 50 patients with HCC. The
      activity within regions of interest placed over tumors was measured, and
      standardized uptake values (SUVs) were calculated by dividing the tissue activity
      by injected dose of radioactivity per unit body weight. SUV ratio (SUVR) was
      expressed as tumor-to-nontumor ratio of SUV. Patients were allocated to 3 groups
      of similar size: group A, SUVR < or = 1.1; group B, 1.1 < SUVR < 1.6; and group
      C, 1.6 < or = SUVR. RESULTS: SUVR significantly correlated with tumor node
      metastasis stage score (p < 0.001) or JIS score (p = 0.022). Survival rate in
      SUVR group C was significantly lower than that in group A (p < 0.001), and close
      to being significantly lower than that in group B. On multivariate analysis, JIS
      scores 2 and > or = 3, SUVR group C were significantly related to survival (All p
      < 0.05). CONCLUSIONS: SUVR was well associated with a tumor staging which is the
      factor of JIS score and with survival, and indicated malignancy and prognosis of
      patients especially with high-grade HCC.

PMID- 18613413
TI  - Principle of perioperative management for hepatic resection and education for
      young surgeons.
AB  - BACKGROUND/AIMS: An expert technique and special anatomical or physiological
      knowledge are needed in the field of hepatic surgery compared to other abdominal
      surgeries. The establishment of basic policy and operative techniques for
      hepatectomy and stepwise training for young hepatic surgeons are necessary.
      METHODOLOGY: We scheduled hepatic resection based on the indocyanine green
      retention rate at 15 minutes and volumetric analysis. Limited resection or
      preoperative portal vein embolization was often performed. RESULTS: Between 1994
      and December 2005, 338 hepatectomies were performed. Operative procedures
      included limited or segmental resection in 215 and hemihepatectomy or more
      extended hepatectomy in 123. Hyperbilirubinemia or hepatic failure after
      hepatectomy was observed in 15 (4%) and hospital death in 10 (3%). Although death
      from hepatic failure was observed in 9 of 152 (6%) between 1994 and 1999, the
      mortality rate has been improved since 2000 (1 of 186 [0.5%]). Senior residents
      start training with step by step hepatectomy from partial resection to
      sectionectomy. Hemi-hepatectomy for normal liver is finally permitted after
      technical consolidation. More complicated hepatectomy must be performed by
      experienced teaching surgeons. CONCLUSIONS: Competent operative techniques under
      experienced surgeons and the achievement of safe resection at each stage are the
      educational policy for hepatectomy.

PMID- 18613414
TI  - Surgery of benign liver tumors: indications for treatment: twenty years'
      experience.
AB  - BACKGROUND/AIMS: The aim of this study is to give an audit of the experiences in
      the Institute of Experimental Surgery, at the University of Szeged, over the past
      2 decades in the form of a retrospective study. METHODOLOGY: Between January 1982
      and December 2001, 132 patients with benign liver tumor (adenoma: 22; focal
      nodular hyperplasia: 27; hemangioma: 83) were treated. A total of 112 patients
      underwent surgery, while 20 asymptomatic cases were merely observed. The mean
      age, the female/male ratio and the size of the tumor in the adenoma cases were
      38.2 years, 20/2 and 7.7cm, while for focal nodular hyperplasia they were 39.4,
      24/3 and 6.3cm, and for hemangioma 49.0, 62/21 and 6.5cm. The results were
      compared and analyzed statistically. RESULTS: Enucleation was performed in 45.4%
      of the patients, nonanatomical resection in 35.6%, segmentectomy in 7%, lobectomy
      in 3.8%, extended lobectomy in 1.5%, stitching in 4.5%, exploration in 2.3% and
      liver transplantation in 0.8%. The mortality was 0.8%. Complications occurred in
      a total of 23.5% of the cases. CONCLUSIONS: Patients with asymptomatic focal
      nodular hyperplasia or hemangiomas must be excluded from surgery. Surgery is
      indicated only when growth or severe complaints are observed. Adenomas must be
      resected because of the precancerous behavior and the danger of bleeding from a
      rupture.

PMID- 18613415
TI  - Sequential magnetic resonance imaging for evaluation of Kupffer cell function.
AB  - BACKGROUND/AIMS: Kupffer cells play an important role in liver regeneration and
      depression of their function is associated with poor outcome. However, there is
      no clinically safe and reliable method for evaluating Kupffer cell function.
      METHODOLOGY: We used magnetic resonance imaging following injection of
      superparamagnetic iron oxide, which is trapped by Kupffer cells, to evaluate
      Kupffer cell function in 14 patients, including 6 with normal liver and 8 with
      obstructive jaundice T1-weighed signal intensity of the liver parenchyma was
      examined every 4 minutes for 60 min after superparamagnetic iron oxide injection.
      RESULTS: Signal intensity values gradually decreased in both groups after
      accumulation of iron in the liver. Serum iron levels equally and significantly
      increased in both groups. In contrast, the values of relative enhancement,
      percentage of signal intensity of precontrast to postcontrast, between 8-20
      minutes after superparamagnetic iron oxide injection were significantly higher in
      obstructive jaundice group than in the control, indicating Kupffer cell
      dysfunction in obstructive jaundiced liver. CONCLUSIONS: These results indicate
      that chronological magnetic resonance imaging with superparamagnetic iron oxide
      is a suitable method for assessment of Kupffer cell function in patients with
      obstructive jaundice.

PMID- 18613416
TI  - The treatment of isolated left-sided hepatolithiasis.
AB  - BACKGROUND/AIMS: It has been over 20 years since percutaneous transhepatic
      cholangioscopic lithotomy (PTCSL) or left lateral segmentectomy with
      postoperative cholangioscopy (POC) was applied in treating isolated left-sided
      hepatolithiasis (ILH). However, their efficacy in treating ILH is not elucidated
      clearly in the literature. METHODOLOGY: A retrospective study was conducted in 59
      patients with ILH undergoing either PTCSL or left lateral segmentectomy with POC
      during the past 22 years. The mean period of followup was 10.8 years (1-22
      years). RESULTS: Hepatolithiasis restricted in the left external hepatic duct
      (LEHD), whose stones can be cleared by left lateral segmentectomy without
      undergoing POC, was only found in 17% (10/59) of the patients with ILH. The
      overall complication rate of left lateral segmentectomy with POC was 22% (4/18),
      and of PTCSL was 17% (7/41). Either in patients with (82%, 9/11 vs. 71%, 12/17; p
      > 0.05) or without intrahepatic ducts (IHDs) stricture (100%, 7/7 vs. 92%, 22/24;
      p > 0.05) in the liver remnant, the rates of complete stone clearance were
      comparable between left lateral segmentectomy with POC and PTCSL. The stone
      recurrence rate and cumulative nonrecurrence rate in patients with IHDs stricture
      in the liver remnant were also comparable between left lateral segmentectomy with
      POC and PTCSL (p > 0.05). Nevertheless, hepatolithiasis did not recur in patients
      without IHD stricture in the liver remnant after left lateral segmentectomy with
      POC, whose stone recurrence rate was lower than those without (0%, 0/7 vs. 50%,
      10/20; p = 0.026) or with (0%, 0/7 vs. 7/12, 58%; p = 0.017) IHDs stricture
      undergoing PTCSL. After undergoing left lateral segmentectomy with POC, the
      cumulative nonrecurrence rate was also higher in patients without IHDs stricture
      in the liver remnant than those with IHDs stricture in the liver remnant (p <
      0.05). CONCLUSIONS: Left lateral segmentectomy with POC and PTCSL have comparable
      efficacy in treating ILH. However, no stone recurs when ILH are completely
      removed without IHD stricture left in the liver remnant after left lateral
      segmentectomy with POC. The presence of IHDs stricture in the liver remnant is
      the major factor contributing to ILH recurrence after successful left lateral
      segmentectomy with POC.

PMID- 18613417
TI  - Genetic distinctions and clinical characteristics of type 1 autoimmune hepatitis
      in Taiwan.
AB  - BACKGROUND/AIMS: The genetic features in Eastern autoimmune hepatitis (AIH)
      patients are seldom surveyed. Previous studies on the linking of human leukocyte
      antigen (HLA) with AIH have highlighted the necessity of evaluating ethnically
      homogeneous populations, but no investigation for Taiwanese patients has been
      reported. This study aims to evaluate the HLA characteristics of Taiwanese AIH
      patients. METHODOLOGY: Medical records of Taiwanese AIH patients (1990-2005) were
      reviewed and the correlation of HLA alleles with disease susceptibility and
      severity was surveyed. HLA typing was performed by polymerase chain reaction
      amplification with sequence-specific primers. RESULTS: Unlike the Western
      reports, HLA-A1, B8, and DR3 were not identified. The most frequently encountered
      was A11 (48.6%). DR4 (35.1%) was less often found than that in Japanese and
      Chinese series. As compared with Taiwanese normal controls, the frequency of B35
      was significantly increased (18.9% vs. 5.4%, odds ratio = 4.072, Pc < 0.001). B35
      postitive patients also had higher pretreatment serum aminotransferase
      concentrations. More of the patients were cholestatic and responded well to a
      lower dose of prednisolone as compared with those reported in the Western
      literature. CONCLUSIONS: HLA-B35 plays a distinct role in susceptibility and
      severity of AIH in Taiwan. Racial genetic backgrounds may account for the
      different results.

PMID- 18613418
TI  - Influence of risk factors for metabolic syndrome and non-alcoholic fatty liver
      disease on the progression and prognosis of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: We investigated a relationship between the risk factors for
      metabolic syndrome, such as obesity, diabetes mellitus, hypertension, and
      hyperlipidemia, and the pathogenesis and outcome of hepatocellular carcinoma
      (HCC). METHODOLOGY: One hundred twenty four patients who underwent curative
      resections for HCC were classified into 3 groups: those patients who were
      positive for hepatitis B surface antigen (group B), those positive for antibody
      to hepatitis C virus (group C), and those negative for both of them (non-B non-C)
      (group NBNC). The preoperative laboratory data, risk factors for metabolic
      syndrome, history of alcohol abuse, and outcome after surgery were investigated.
      The presence of non-alcoholic steatohepatitis (NASH) was also evaluated. RESULTS:
      The incidence of diabetes mellitus, hyperlipidemia, and alcohol abuse, and the
      serum level of triglyceride were significantly higher in group NBNC than in
      groups B or C. The risk factors for metabolic syndrome tended to lower the
      survival rates in group B and C, but not in group NBNC. Three of the 37 non-B non
      C patients were associated with NASH. CONCLUSIONS: It is suggested that the
      pathogenesis of non-B non-C HCC may be more closely associated with the risk
      factors for metabolic syndrome than that of hepatitis virus related HCC.

PMID- 18613419
TI  - Effect of a new adjuvant systemic interferon alpha, 5-fluorouracil and cisplatin
      on advanced hepatocellular carcinoma with macroscopic portal invasion.
AB  - BACKGROUND/AIMS: Despite an adequate hepatic resection, theprognosis of the
      patients with hepatocellular carcinoma (HCC) that have macroscopic tumor thrombus
      in the portal vein has still been poor. The prognosis of those patients and was
      investigated the significance of postoperative adjuvant therapy was discussed in
      this study. METHODOLOGY: Twenty five patients who had Vp2 or more portal invasion
      were included in this study. Those patients were retrospectively divided into 2
      groups: the systemic interferon alpha, 5-Fluorouracil (FU) and cisplatin group (n
      = 10, IFN+ chemo group); and the no adjuvant therapy group (n = 15, control
      group). RESULTS: The overall survival rate was significantly higher in the
      IFN+chemo group compared with the control group. There was no significant
      difference between the 2 groups in regard to the disease-free survival rate.
      However, a difference in the recurrence pattern was observed between the 2
      groups. In the IFN+chemo group, 3 of 6 patients with a recurrence had a single
      tumor in the remnant liver. While in the control group, 10 of 11 recurrent
      patients had either distant metastasis or multiple recurrences in the residual
      liver. CONCLUSIONS: Our new adjuvant systemic therapy including interferon alpha,
      5FU and cisplatin for advanced HCC with macroscopic portal invasion is promising.

PMID- 18613420
TI  - Hepatectomy for hepatocellular carcinoma patients who meet the Milan criteria.
AB  - BACKGROUND/AIMS: Although hepatocellular carcinoma patients who meet the Milan
      criteria are optimal candidates for liver transplantation, most such patients in
      Japan have been treated without liver transplantation. METHODOLOGY: In this
      retrospective analysis, the patient selection criteria were (1) admission between
      1992 and 2005, (2) fulfillment of the Milan criteria, (3) classification within
      the Barcelona Clinic Liver Cancer stages A1-A4, and (4) no previous anticancer
      treatment. RESULTS: Of 451 patients who met the selection criteria, 162 underwent
      hepatectomy. The proportion of patients who underwent hepatectomy was 58% of 106
      with stage A1 and 29% of 345 with stages A2-A4. For patients with stages A2-A4,
      the survival probability after hepatectomy at 3, 5, and 7 years was 89%, 70%, and
      61%, respectively. There were no significant differences in survival time between
      stages A1 and stages A2-A4 after hepatectomy. Among patients with Child-Pugh
      scores of 5 and 6 in stages A2-A4, 51% and 29% underwent hepatectomy,
      respectively. CONCLUSIONS: Hepatectomy may be an appropriate first-line treatment
      option for patients with stages A2-A4 who meet the Milan criteria, when they have
      a good hepatic reserve and a long waiting time for liver transplantation.

PMID- 18613421
TI  - Surgical treatment and adjuvant chemotherapy in hepatocellular carcinoma patients
      with advanced vascular involvement.
AB  - BACKGROUND/AIMS: In advanced hepatocellular carcinoma (HCC) with vascular
      involvement of major vessels, patients have a poor prognosis after surgical
      treatment. METHODOLOGY: Patient outcomes after surgical resection and the
      usefulness of adjuvant chemotherapy were examined in 12 patients with major
      hepatic vessel involvement who underwent hepatectomy with combined resection of
      major blood vessels. RESULTS: The main portal vein was resected in 8 patients,
      the inferior vena cava in 3, hilar bile duct in 2 and hepatic artery in 1. Eleven
      patients underwent hemihepatectomy and 1 underwent segment 4 and 5 resection. The
      portal branch was repaired by venoplasty. The vena cava wall was repaired by
      suture closure. The hepatic artery was replaced by end-to-end anastomosis. The
      bile duct was repaired by Roux-en-Y hepaticojejunostomy. Although 2 patients had
      biliary leakage, there were no postoperative complications in 10 patients. The
      tumor recurrence rate was 83% in the early period and cancer death within 1 year
      was observed in 6 (50%), while 3 with tumor recurrence survived for more than 2
      years and 2 survived without recurrence. In 233 HCC patients who underwent
      hepatectomy, 10 patients including 2 present cases received adjuvant chemotherapy
      at the time of tumor recurrence and 2 had complete responses. While in 11
      patients receiving chemotherapy without resection, the response rate using
      Gemcitabine (66%) was higher than that using low dose Cisplatin plus 5
      Fluorouracil (22%). CONCLUSIONS: Complete surgical resection combined with main
      vascular resection could be safely performed in most advanced stage HCC patients
      and adjuvant chemotherapy in the early period after resection would be necessary,
      which may achieve longer survival in some patients even in the advanced stage.

PMID- 18613422
TI  - Hepatitis B viral genotype in Taiwanese patients with acute hepatitis B.
AB  - BACKGROUND/AIMS: The correlation of HBV genotype with clinical outcome has been
      recognized in chronic hepatitis B patients. However, there are few reports on the
      distribution and clinical significance of HBV genotypes in acute hepatitis B
      patients. METHODOLOGY: Nineteen acute hepatitis B patients were identified and
      their HBV genotypes were determined. The serological and clinical data were thus
      compared between patients with different HBV genotypes. RESULTS: Two HBV
      genotypes (B and C) were found in the patients. Genotype B was more predominant
      than genotype C (12 vs. 7). The age, serum alanine aminotransferase level, serum
      alpha-fetoprotein level, and serum HBV DNA level were not significantly different
      between patients infected with genotype B or C. None of them had persistent HBsAg
      for longer than 6 months. CONCLUSIONS: Genotype B predominates in acute hepatitis
      B patients in Taiwan; however, the clinical features between genotype B and
      genotype C patients are comparable.

PMID- 18613423
TI  - Strong association between frequency of intermittent inflow occlusion and
      transient increase in serum liver enzymes after hepatic resection.
AB  - BACKGROUND/AIMS: Although significantly higher serum levels of liver
      transaminases are commonly observed after hepatic resection, the factors
      responsible for the increase and the association between the increase and the
      postoperative course remain unclear. METHODOLOGY: The study population comprised
      70 patients who had undergone hepatic resection except hepatectomy with vascular
      and biliary reconstruction. The relation between the perioperative factors and
      postoperative aspartic aminotransferase (AST) and alanine aminotransferase (ALT)
      elevations were analyzed. Outcome parameters, i.e., postoperative total bilirubin
      level, hospital stay and complications were also analyzed. RESULTS: The average
      maximum postoperative serum AST and ALT levels were 444.6 IU/L and 390.1 U/L.
      None of the preoperative factors examined, such as AST, ALT, associated liver
      disease, Liver Damage Classification, intraoperative hypotension, intraoperative
      blood loss or types of liver resection, were significantly correlated with liver
      enzyme elevations. The only factor that was significantly correlated was
      frequency of intermittent inflow occlusion (p < 0.001). The elevations of AST and
      ALT were not significantly correlated with length of hospital stay and
      postoperative serum bilirubin level. ALT also was not correlated to
      complications, whereas AST was significantly correlated to the frequency of the
      postoperative complications. CONCLUSIONS: The frequency of intermittent inflow
      occlusion is the only factor that affects the postoperative enzyme elevation.

PMID- 18613424
TI  - Impaired liver regeneration after synchronous liver and colon resection in rats.
AB  - BACKGROUND/AIMS: Hepatectomy combined with colectomy is the preferred treatment
      for patients with synchronous colorectal cancer and hepatic metastasis. However,
      the effects on hepatic reserve function of combining colectomy with hepatectomy
      are unclear. The purpose of this study was to determine liver regeneration and
      functions after hepatectomy with and without colectomy. METHODOLOGY: 23 rats
      underwent 70% hepatectomy (Hx group) and 23 rats underwent 70% hepatectomy with
      ileocecal resection (HCx group), and 6 rats just after surgery (day 0) underwent
      simple celiotomy. On days 0, 1, 2, 3 and 7 after surgery, the remnant liver
      weight, DNA synthesis rate, malondialdehyde concentration, hepatic Adenosine
      monophosphate, ADP, ATP, serum hyaluronic acid concentration and endotoxin level
      in the portal blood were measured. RESULTS: In HCx group, the hepatic DNA
      synthesis rate on day 1 (p < 0.01) and the liver weight on day 7 (p < 0.05) were
      significantly lower, hepatic malondialdehyde concentration on days 1 and 2 (p <
      0.05) was significantly higher and serum hyaluronic acid and portal endotoxin
      levels on day 1 were significantly higher (p < 0.01 and p < 0.05, respectively).
      CONCLUSION: Addition of colectomy to hepatectomy impairs regeneration and
      endothelial cell function of the remnant liver; the impairment is associated with
      increased levels of portal endotoxin and hepatic lipoperoxide.

PMID- 18613425
TI  - Hepatectomy for hepatocellular carcinoma in a community hospital: the importance
      of surgeon procedural volume in operative outcomes.
AB  - BACKGROUND/AIMS: Hospital procedural volume is shown to be important in affecting
      the postoperative mortality after major cancer surgery. Recent analysis
      demonstrates that hospital and surgeon volume effects on postoperative outcomes
      after major operations are actually interdependent and surgeon volume may be more
      important. The effects of hospital and surgeon volume on postoperative outcomes
      after hepatectomy for hepatocellular carcinoma are uncertain. METHODOLOGY: A
      retrospective study was conducted of 65 patients who had undergone hepatectomy
      for hepatocellular carcinoma in a 6-year period. A specialized hepatobiliary team
      was set up in 2002 in the Kwong Wah Hospital. The postoperative outcomes of
      patients operated between 1999 and 2001 (Group 1) were compared to that of those
      treated between 2002 and 2004 (Group 2). RESULTS: The hospital mortality was 8.3%
      in Group 1 and 3.4% in Group 2 (p = 0.393). The postoperative morbidity was 50%
      in Group 1 but decreased to 27.6% in Group 2, though the difference was not
      statistically significant (p = 0.056). The median hospital stay of patients in
      Group 2 was significantly shorter than that of those in Group 1 (17 days vs. 11
      days, p = 0.005). CONCLUSIONS: Despite the unchanged hospital volume,
      concentration of patients into a single team increases surgeon volume and
      improves postoperative outcomes after hepatectomy for hepatocellular carcinoma.

PMID- 18613426
TI  - Is an elderly recipient a risk for living donor adult liver transplantation?
AB  - BACKGROUND/AIMS: In cadaveric liver transplantation, it has been reported that
      elderly recipients over 60 years are at risk because of high incidence of
      complication and malignancy. However, in living-donor adult liver transplantation
      (LDALT), it is unclear whether the elderly recipient is risky or not risky. In
      this study, the outcome after LDALT of elderly patients has been evaluated.
      METHODOLOGY: One hundred twenty two consecutive LDALT recipients were studied.
      The recipients were divided into an elderly group (older than 60 yrs, n = 21),
      and a control group (younger than 60 yrs, n = 101). Comparative examination of
      background factors, postoperative complications and de novo malignancy was
      carried out. RESULTS: Elderly patients more frequently received transplantation
      for hepatocellular carcinoma. Pretransplant liver damage such as Child-Pugh, MELD
      or bilirubin level was same among the groups. There was no significant difference
      in posttransplant complications except renal failure. Postoperative renal failure
      (postoperative creatinine level over 2mg/dL) occurred in 29% (n = 5) of the
      elderly group vs. 8% (n = 6) of the control group. De novo malignancy occurred in
      1 case (lung) in the elderly group and 1 case (Vater) in the control group. In
      the control group, the 1, 3 and 5 year patient survival rates were 78.5%, 73.1%
      and 71.4%, respectively. And in the elderly group, the 1, 3 and 5 year patient
      survival rates were 85.7%, 81.0% and 70.8%, respectively. CONCLUSIONS: It may be,
      we concluded that living donor adult liver transplantation is good treatment for
      end stage liver diseases in elderly recipients over 60 years. However caution
      should be taken in the administration of medicine, including immunosuppressants
      or antibiotics, do to a propensity for postoperative renal failure in elderly
      recipients.

PMID- 18613427
TI  - Chronic hepatitis C: hepatic fibrosis evolution after ineffective specific
      treatment.
AB  - BACKGROUND/AIMS: Specific treatment of chronic hepatitis C is effective in 50% of
      patients, improving the liver's fibrosis, necroinflammatory changes and
      steatosis. However, in patients still viremic after treatment the extension of
      these benefits remains doubtful. The evolution of the disease in this group and
      its relationship to demographic data, biometric indices and time lapse between
      biopsies was evaluated. METHODOLOGY: In 141 patients, paired biopsies were
      classified and compared according to fibrosis grading. Necroinflammation,
      steatosis, demographic data (age and gender), body mass index (BMI) and time
      lapse between biopsies were compared with fibrosis grading. RESULTS: The grade of
      fibrosis of the patients, after approximately 3.5 years time lapse between
      biopsies, could be classified into 4 groups; Improved: 29 (20.0%), Unaltered: 64
      (45.0%), Worsened: 48 (34%) and Cirrhotic: 14 (9.93%). For necroinflammation, the
      Improved/Unaltered groups were statistically similar but different from the
      Worsened and Cirrhotic. The mean age, BMI and time lapse between biopsies were
      statistically similar in all groups. Steatosis occurred in 35 (24.82%) between
      biopsies and its incidence was reduced in the Worsened and Cirrhotic groups.
      CONCLUSIONS: Fibrosis turned into cirrhosis in a significant number of patients,
      after a short time lapse. The reverse correlation of steatosis to fibrosis and
      its occurrence during the time lapse between biopsies suggests it might induce
      hepatic necrosis and contribute to fibrogenesis.

PMID- 18613428
TI  - Primary hepatic carcinoid tumour: a detailed account of imaging findings.
AB  - Primary hepatic carcinoid tumours are very rare and less than 60 cases have been
      reported in the literature. This study reports a 35-year-old female with 2
      synchronous primary hepatic carcinoid tumours in her right hepatic lobe. She was
      examined with various imaging investigations including ultrasound scan, computed
      abdominal tomography, magnetic resonance imaging, mesenteric angiography and
      positron emission tomography. She underwent right hepatectomy and the lesions
      were proven to be carcinoid tumours. She has been free of disease for more than 5
      years of follow-up and the diagnosis of primary hepatic carcinoid tumour is
      suggested.

PMID- 18613429
TI  - Adult-to-adult living donor liver transplantation in severe portosystemic shunt
      cases.
AB  - To date, the need for spontaneous portosystemic shunt division during adult-to
      adult living donor liver transplantation (LDLT) remains unknown. This study
      reports 2 patients with large portosystemic shunts who required LDLT. The first
      patient was a 40-year-old male with liver cirrhosis due to hepatitis C. The
      angiogram showed splenosystemic shunts with hepatopetal flow. Shunt occlusion was
      not performed after implanting a small-size graft because sufficient portal blood
      flow was observed. On the first postoperative day, portal blood flow was not
      detected; therefore shunt occlusion was per formed and the portal blood flow was
      restored. The second patient was a 51-year-old female with primary biliary
      cirrhosis. Marked collateral circulation with hepatofugal flow was observed.
      Shunt occlusion was performed after implanting a medium-size graft. Postsurgery,
      hepatopetal portal blood flow was observed and the postoperative course was
      satisfactory. These cases demonstrate that large portosystemic shunts should be
      ligated to maintain adequate portal blood flow that corresponds to the graft
      volume.

PMID- 18613430
TI  - Living donor liver transplantation with extra-small graft; inflow modulation
      using splenectomy and temporary portocaval shunt.
AB  - In living donor liver transplantation in adults, a strategy to manage unexpected
      small graft is essential. The patient was a 47-year-old female with endstage
      liver disease secondary to hepatitis C with hepatocellular carcinoma, and the
      donor was a 20-years-old female. Although the estimated left lobe graft volume
      was 379g and 35.8% of the standard liver volume of the recipient, the actual
      volume was just 250g, representing only 23% of the standard liver volume. After
      implantation of this graft, a splenectomy followed by end-to-side portocaval shut
      was done, both for modulating excessive portal inflow to the small graft. Despite
      the excellent initial graft function with hepatopetal portal flow and an
      excellent gold-colored bile from the graft, the graft portal flow decreased with
      liver regeneration 4 days after transplantation. So the closure of the portocaval
      shunt was carried out. Since then there was a good postoperative course without
      any sign of small graft syndrome. She was discharged from the hospital at 21 days
      after transplantation. This type of inflow modulation may allow us to manage such
      an extra-small graft. However, careful post-transplant monitoring of the portal
      flow is essential for gaining an acceptable outcome.

PMID- 18613431
TI  - Successful treatment for hepatocellular carcinoma with main portal vein tumor
      thrombi by 3-dimensional conformal radiation therapy combined with transarterial
      chemoembolization.
AB  - In hepatocellular carcinoma (HCC), main portal vein (MPV) tumor thrombi are
      considered to indicate an advanced stage. Transarterial chemoembolization (TAE)
      is contraindicated in patients with MPV tumor thrombi because of the risk of
      hepatic functional deterioration. On the other hand, 3-dimensional conformal
      radiation therapy (3D-CRT) can focus a high dose of radiation on a small area and
      seems to be suitable for targeting tumor thrombi within the portal vein. Here, we
      describe 2 HCC cases with MPV tumor thrombi, who were successfully treated by 3D
      CRT combined with TAE. In case 1, 3D-CRT successfully eliminated tumor thrombi
      within the MPV, and offered the opportunity of further TAE for intrahepatic
      tumor. The patient remained alive 5 months after the last TAE without liver
      function deterioration and without a viable HCC. In case 2, following this
      combined therapy, intrahepatic HCC and MPV tumor thrombi regressed. However, the
      MPV was not recanalized and subsequently liver function deteriorated.
      Fortunately, thrombi remaining within the MPV did not progress, and a collateral
      circulation developed around the MPV. This patient remained alive 12 months after
      treatment without a viable intrahepatic HCC. Therefore, although 3D-CRT combined
      with TAE cannot be routinely recommended because of anticipated hepatic
      functional deterioration, it can be cautiously considered for patients with MPV
      tumor thrombi.

PMID- 18613432
TI  - Isolated loop pancreatic remnant drainage following pancreaticoduodenal
      resection.
AB  - BACKGROUND/AIMS: Using technology-intensive postoperative critical care,
      interventional radiology and consequent better management of pancreaticojejunal
      anastomosis (PJA) leaks, the perioperative mortality of pancreaticoduodenal
      resection (PDR) at high volume Western centers ranges from 1-5%. Facilities for
      such sophisticated care are not available in most hospitals in the developing
      world. We hypothesized that by using an isolated Roux loop for the PJA to
      minimize the consequences of a leak, it might be feasible to perform PDR with
      comparable results. METHODOLOGY: From August 1996 to December 2002, 125
      consecutive patients (98 males and 27 females with a mean age of 54 years) with
      peri-ampullary or pancreatic head carcinomas underwent PDR with the PJA made to
      an isolated Roux loop of jejunum. A prospectively maintained database was
      analyzed for perioperative mortality, morbidity, hospital stay and costs.
      RESULTS: The perioperative mortality was 7 (5.6%) and morbidity 52 (42%).
      Pancreatic fistulae developed in 15 (12%) patients and biliary or intestinal
      fistulae developed in 1(0.8%) patient each. Five (4%) patients underwent
      relaparotomy. The median hospital stay was 13 days (6-46 days). CONCLUSIONS:
      Using an isolated Roux loop for PJA, centers with limited resources can perform
      PDR to achieve perioperative outcomes comparable to those reported from more
      sophisticated centers.

PMID- 18613433
TI  - Survival rate of pancreatic cancer in elderly patients.
AB  - BACKGROUND/AIMS: As the population ages, many elderly people will be diagnosed
      with pancreatic cancer. This study is to investigate the current survival rates
      for patients aged > or = 70 years diagnosed with pancreatic cancer and to
      identify prognostic factors, which will help in choosing optimal therapies for
      individual patients. METHODOLOGY: Information was gathered retrospectively for 81
      patients aged > or = 70 years with pancreatic cancer. Clinical parameters,
      treatments received and survival curves from initial treatment were analyzed.
      RESULTS: Overall median survival was 6.2 months. Patients who underwent surgical
      therapy had the best median survival rate of 26.5 months, followed by patients
      receiving chemotherapy (6.6 months), chemoradiotherapy (5.7 months) and best
      supportive care (3.4 months). Further analysis showed that the median survival of
      chemotherapy and chemoradiotherapy groups was 8.1 and 11.3 months for stage III,
      6.2 and 3.9 months for stage IV respectively. Independent negative prognostic
      factor for survival were Karnofsky performance status < or = 80 and presence of
      distant metastases. CONCLUSIONS: Long-term survival can be achieved through
      surgical resection in patients aged > or = 70 at early stage. Chemotherapy should
      be considered for patients with better expected survival. Radiation therapy
      should be applied for stage III patients. However, it was not associated with
      survival benefit for stage IV. Karnofsky performance status and distant
      metastases are independent prognostic factors.

PMID- 18613435
TI  - Mucinous cystadenocarcinomas of the pancreas.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the clinicopathologic
      characteristics, diagnosis and treatment of mucinous cystadenocarcinomas (MCACs)
      of the pancreas. METHODOLOGY: This is a retrospective review of 6 patients who
      underwent curative resection for MCACs of the pancreas in the Department of
      General Endocrine and Transplantation Surgery, Medical University of Gdansk from
      1994-2004. Clinical presentation, radiological evaluation and surgical procedures
      were analyzed. RESULTS: There were 4 women and 2 men. Median age was 59 years.
      Patients complained of abdominal pain, nausea, vomiting and weigh loss, 2 of them
      had jaundice and 1 gastrointestinal (GI) bleeding. Ultrasonography and computed
      tomography showed cystic lesions. Solid component was found in 3 cases. Three
      endoscopic retrograde cholangiopancreatographys (ERCPs) were unhelpful in
      differentiating between malignant tumor and benign lesion. All patients underwent
      resection. In 3 cases Whipple resection, in 1 case Traverso - Longmire resection
      and in 2 cases distal pancreatectomy was performed. Histopathologically, all
      tumors were mucinous cystadenocarcinomas. CONCLUSIONS: Diagnostic accuracy for
      cystic pancreatic neoplasm is still limited. Surgical resection is recommended in
      all cystic tumors that are not clearly defined.

PMID- 18613434
TI  - Second surgery after a pancreaticoduodenectomy in patients with periampullary
      malignancies.
AB  - BACKGROUND/AIMS: Few case reports have previously documented a second surgery
      after pancreaticoduodenectomy due to recurrence or other reasons in patients with
      periampullary malignancies. The present report summarized the experience of this
      clinic with secondary surgery after Pancreaticoduodenectomy (PD). METHODOLOGY:
      During the past 7 years, 7 out of 95 patients with periampullary malignancies
      underwent a second surgery after pancreaticoduodenectomy at this institution. The
      clinical courses of these patients are presented and 2 interesting cases are
      shown in the present study. RESULTS: One patient with lower bile duct
      adenocarcinoma underwent a remnant splenopancreatectomy due to pancreatic
      recurrence 36 months after pancreaticoduodenectomy. The other patient with lower
      bile duct adenocarcinoma underwent a hepatectomy due to a solitary liver
      metastasis 47 months after a pancreaticoduodenectomy. These 2 patients have
      survived 4 and 13 months after the second surgery. In the 7 patients requiring
      secondary surgery, 5 underwent the procedure due to recurrent disease, and 4 of
      the 5 received the second surgery to remove the lesion. The mean interval between
      pancreaticoduodenectomy and the second operation was 32 months in the 5 patients
      with recurrent disease and 27 months in the all 7 patients. One of the 5 patients
      died of recurrent disease only 5 months after the second procedure because the
      surgery was a palliative bypass. However, the other 3 survived more than 1 year
      after the resection of the lesion at the recurrent site. CONCLUSIONS: The present
      study reports 2 rare cases with lower bile duct adenocarcinoma in which a
      recurrent tumor was removed after pancreaticoduodenectomy. In this study, 4
      patients undergoing a curative re-operation survived more than 1 year after the
      surgery. The present study was small, but the findings are significant because of
      the scarcity of reports of patients undergoing secondary surgery after PD.

PMID- 18613436
TI  - Isoenzymes A and B of N-acetyl-beta-D-hexosaminidase in serum and urine of
      patients with pancreatic cancer.
AB  - BACKGROUND/AIMS: Adenocarcinoma is the most frequent malignant tumor of the
      pancreas. Biochemical diagnostics of pancreatic adenocarcinoma is based on
      determination of carcinoma antigen (CA 19-9) in the blood. Determination of N
      acetyl-beta-hexosaminidase (HEX) in the serum and urine was used in diagnosis of
      renal and gastric cancers. Therefore the aim of our research was to estimate N
      acetyl-beta-hexosaminidase (HEX) and its isoenzymes (HEX A and HEX B) in the
      serum and urine as potential markers of pancreatic cancer. METHODOLOGY: Serum and
      urine samples were collected from 15 patients with adenocarcinoma of the pancreas
      and 15 healthy persons. The activity of N-acetyl-beta-hexosaminidase and its
      isoenzymes (A and B) was determined by a colorimetric method of Zwierz et al.
      Absorbancy of the yellow product of the colorimetric reaction was determined on
      the microplate reader EL(x)800 produced by BIO-TEK. The concentration of HEX, HEX
      A and B was expressed in pKat/mL, and the specific activity in pKat/mg of
      protein. Protein concentration was determined in the serum by the biuret and in
      the urine by the Lowry method, respectively, and expressed in mg/mL. RESULTS: The
      concentration and specific activity of HEX and its isoenzyme A were significantly
      higher in the serum and urine of pancreatic cancer patients in comparison with
      the concentration and specific activity in the serum and urine of healthy people.
      CONCLUSIONS: The results suggest that the activity of HEX and its isoenzyme A
      determined in the serum and urine can be used as a potential marker of pancreatic
      adenocarcinoma.

PMID- 18613437
TI  - The morbidity, mortality, and prognostic factors for ampullary carcinoma and
      distal cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Ampullary carcinoma and distal cholangiocarcinoma are
      potentially more amenable to pancreaticoduodenectomy for long-term survival than
      pancreatic carcinoma. The aims of this study are to evaluate experience with
      ampullary carcinoma and distal cholangiocarcinoma at a single institution.
      METHODOLOGY: Seventy-two consecutive patients with ampullary carcinoma and distal
      cholangiocarcinoma who underwent radical resection at Chiba University Hospital
      from 1985 to 2001. Clinicopathological factors for survival were evaluated by
      univariate and multivariate analyses in a retrospective study. RESULTS:
      Pancreaticoduodenectomy was performed in 37 of 38 patients for ampullary
      carcinoma and 29 of 34 patients for distal cholangiocarcinoma. The morbidity
      rates of patients with ampullary carcinoma and distal cholangiocarcinoma were
      21.1% and 20.6%, and mortality rates were 0% and 2.9%, respectively. The
      cumulative 5-year survival rates in cases of ampullary carcinoma and distal
      cholangiocarcinoma were 63% and 45%, respectively. By univariate analysis,
      pancreatic invasion, lymph node metastasis, and duodenal invasion were
      significant prognostic factors for ampullary carcinoma. Perineural invasion and
      histological grade, but not lymph node metastasis, were significant factors for
      distal cholangiocarcinoma. Multivariate analysis indicated that lymph node
      metastasis was the only independent prognostic factor for ampullary carcinoma,
      and that perineural invasion was the only independent prognostic factor for
      distal cholangiocarcinoma. CONCLUSIONS: The overall mortality of 1.4% and the
      cumulative 5-year survival rates for ampullary carcinoma and distal
      cholangiocarcinoma are acceptable. Ampullary carcinoma with lymph node metastasis
      and distal cholangiocarcinoma with perineural invasion have higher risk of
      recurrence.

PMID- 18613438
TI  - Preoperative evaluation of malignancy in intraductal papillary mucinous neoplasms
      of the pancreas, especially in relation to dysplastic epithelial changes.
AB  - BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms have a better prognosis
      than ductal adenocarcinomas of the pancreas. The aim of this study was to
      evaluate the malignant potential of IPMNs by their preoperative images.
      METHODOLOGY: Forty-three intraductal papillary mucinous neoplasms were divided
      into 3 duct ectatic types using preoperative images (the main duct type, the
      branch duct type, and the mixed type), and into 2 groups using resected specimens
      (the malignant group including severe dysplasia based on the WHO classification
      and the benign group). The diameters of the tumor, main pancreatic duct and mural
      nodule were measured on the images. RESULTS: Two thirds of main duct type cases
      were in the malignant group. For the branch duct and mixed types, the diameters
      of the tumor and detectable mural nodules were larger in the malignant group than
      in the benign group. A tumor diameter larger than 3.5cm and a mural nodule
      diameter larger than 6mm were risk factors for malignancy (p < 0.05).
      CONCLUSIONS: The main duct type, a tumor larger than 3.5cm of the branch duct or
      mixed type, and a mural nodule larger than 6mm were all indicators of malignancy
      risk.

PMID- 18613439
TI  - Acinar cell carcinoma of the pancreas: is the absence of neuroendocrine component
      related to a more malignant behavior?
AB  - BACKGROUND/AIMS: Acinar cell carcinomas are uncommon malignant tumors of the
      pancreas, accounting for 1-2% of all the cases of exocrine pancreatic tumor. Some
      authors have estimated acinar cell tumors to be as aggressive as ductal
      adenocarcinoma of the pancreas whereas other series showed acinar cell tumors to
      have a favorable clinical outcome. This discrepancy in prognosis may be related
      to the cellular components of the tumor. METHODOLOGY: With the aim to evaluate
      the possible relationship between the presence of neuroendocrine differentiation
      and behavior of these tumors, the authors reviewed all patients presenting acinar
      cell carcinoma of the pancreas in the last 5 years with emphasis in the
      immunohistochemical evaluation. RESULTS: Four patients presented neuroendocrine
      differentiation on immunohistochemical evaluation and had a more benign outcome.
      Two patients without neuroendocrine component had a disseminated disease at
      presentation. This data suggests that this tumor is less aggressive than ductal
      adenocarcinoma and even with nodal involvement, long-term survival after complete
      resection can be achieved. CONCLUSIONS: It is possible that the absence of
      neuroendocrine component may be related to a less favorable outcome and adjuvant
      therapy may be necessary. Due to the rarity of this pancreatic tumor, this
      relationship remains to be confirmed with a multicentric study including a larger
      number of patients.

PMID- 18613440
TI  - Late postoperative quality of life following pancreatic head resections.
AB  - BACKGROUND/AIMS: To evaluate health-related quality of life (HRQoL) in patients
      that have undergone pancreatic resection and compare the results with
      representative population samples in early and late stage evaluations. Also, this
      study aims to observe possible associations with postoperative complications.
      METHODOLOGY: Twenty-seven single-institute patients operated on during a 3-year
      period due to a benign or malignant process of the periampullary region. HRQoL
      was measured by the 15D instrument. Data were compared with those obtained from
      representative Finnish general population samples. RESULTS: Twenty-five patients
      were interviewed in the early stage (24 months postoperatively). Fifteen had a
      benign and 12 a malignant disease. No differences were found in the postoperative
      HRQoL when the nature of the disease or the postoperative complications were
      considered. When compared with the general population in the early stage, HRQoL
      was lower in the study group in whole, and also when sleep, elimination (bladder
      or bowel function) and sexual activity were considered separately. In the late
      stage evaluation (110 months postoperatively) the study group consisted of 15
      surviving patients. There were no differences in comparison to the general
      population. Also when comparing the same patients in 2 evaluation points (24 and
      110 months), we did not find any difference in any of the 15D parameters.
      CONCLUSIONS: Postoperative HRQoL deteriorated in comparison to general population
      in the early stage but there were no differences in the late stage. This study
      encourages us to continue the use of the 15D at least as a part of HRQoL
      evaluation, because it allows comparisons between different diseases and the
      general population.

PMID- 18613442
TI  - A modified technique of pancreatojejunostomy.
AB  - The leading cause of morbidity following pancreatic resections is constituted by
      pancreatic fistulae. Several methods are used for the prevention of this problem,
      although the ideal solution is still being searched for. The authors modified the
      technique of single-layer end-to-side pancreatojejunostomy, creating the
      anastomosis with special interrupted stitches. 45 patients were operated on for
      benign or malignant pancreatic diseases and none of them had pancreatic fistula
      as a complication. The method is technically easy to perform and seems to be
      safe.

PMID- 18613441
TI  - Prophylactic irrigation around a pancreaticojejunostomy for the treatment of a
      pancreatic fistula after a pancreaticoduodenectomy in patients with a risky
      pancreatic remnant.
AB  - BACKGROUND/AIMS: Postoperative morbidity after a pancreaticoduodenectomy remains
      high mainly due to pancreatic fistula, but effective methods to prevent the
      development of pancreatic fistula have yet to be established. The present study
      prospectively investigated whether postoperative prophylactic irrigation around
      the pancreaticojejunostomy might be able to prevent eventual pancreatic fistula
      and infectious complications after a pancreaticoduodenectomy. METHOD: Among 75
      patients undergoing a pancreaticoduodenectomy between 2003 and 2005, 50 patients
      in whom the drain amylase level on postoperative day 1 were 1,500 IU/L or more
      were selected for the present study. Twenty-six of the 50 patients underwent
      postoperative prophylactic 72-hour continuous irrigation around the
      pancreaticojejunostomy starting from postoperative day 1 (Irrigation group). On
      the other hand, 24 of them did not undergo such irrigation (Non-irrigation
      group). The incidence of pancreatic fistula, infectious complications, delayed
      gastric emptying, and the length of hospital stay were then compared between the
      2 groups. RESULTS: The incidences of pancreatic fistula, wound infection, drain
      infection, sepsis, delayed gastric emptying, overall morbidity, and length of
      hospital stay were found to be significantly less in the irrigation group than in
      the non-irrigation group. CONCLUSIONS: Prophylactic irrigation may possibly be
      able to prevent the occurrence of pancreatic fistula and infectious complications
      after a pancreaticoduodenectomy in patients with a risky pancreatic remnant.

PMID- 18613443
TI  - Continuous irrigation with suction started at early days after pancreatic surgery
      prevents severe complications.
AB  - The management of pancreatic leakage is important after pancreatic resection
      because such leakagge can be associated with additional complications. In this
      paper, we present a new therapy "irrigation with suction" after pancreatic
      surgery. The addition of suction permits the start of irrigation early after
      surgery and prevents severe post-operative complications. Between January 1995
      and June 2003, 29 consecutive patients underwent surgical treatment of the
      pancreas for a variety of indications. Among them, 18 patients were treated with
      continuous irrigation with suction prophylactically. In these 29 patients, we did
      not encounter any additional complications such as intraabdominal hemorrhage or
      abscess formation. A representative case report demonstrates the application of
      this treatment. The irrigation with suction therapy was started on the first post
      operative day after the pylorus-preserving pancreatoduodenectomy with left
      lobectomy of the liver. CT with irrigation of contrast reagent showed that the
      reagent did not spread to the uninvolved abdominal area, and the patient did not
      develop hemorrhage or abscess. It seems that continuous irrigation with suction
      therapy was effective in preventing additional serious complications after
      pancreatic resection.

PMID- 18613444
TI  - Postoperative hemorrhage after major pancreatobiliary surgery: an update.
AB  - In recent years, mortality associated with pancreaticoduodenectomy has come down
      to less than 5% but morbidity still remains high. Pancreatic fistula is one of
      the most common complications following pancreaticoduodenectomy.
      Postpancreatectomy hemorrhage is a rare but disastrous complication and
      associated with poor outcome. Early bleeding is usually due to some surgical
      mishap, but the management is simpler. Delayed hemorrhage has more complex
      pathophysiology and requires a multimodality approach for its management. In this
      paper, we review the recent articles related to postoperative hemorrhage after
      major pancreatobiliary surgery. Here we discuss the incidence, cause,
      investigations and management of early and late postoperative hemorrhage.

PMID- 18613445
TI  - Importance of surgical audit: postop complication of gastric cancer surgery among
      different units.
AB  - BACKGROUND/AIMS: Comparative surgical audit is a very important issue in surgical
      practice. The POSSUM (Physiological and Operative Severity Score for the
      enumeration of Morbidity and mortality) system has been proposed as the most
      efficient risk adjusting tool which can be used to compare surgical outcome among
      different units. POSSUM was applied for risk-adjusted auditing of different units
      in a single hospital. METHODOLOGY: In total, 357 gastric cancer patients who
      underwent radical resection or palliative procedures were analyzed
      retrospectively to evaluate predictive value of POSSUM scoring system and postop
      morbidity was compared among 5 different units in a single hospital. RESULTS:
      POSSUM predicted well by correct analysis; the observed to expected morbidity
      ratio (O:E ratio) was 1.01 for patients overall. But there were significant
      differences in complication rates among different units, the O: E ratio ranging
      from 0.7-1.63. CONCLUSIONS: POSSUM is a credible tool for predicting postop
      morbidity in gastric surgery. It provides risk-adjusted morbidity which can be
      compared directly. There was surprising difference in surgical outcome among
      different units of a single hospital, this demands more prospective researches to
      evaluate surgical outcome of different units. We conclude gastric cancer surgery
      should be performed in specialized centers.

PMID- 18613446
TI  - Concurrent assessment of reservoir and emptying of the stomach for dyspepsia
      patients.
AB  - BACKGROUND/AIMS: We simultaneously examined the reservoir function of the stomach
      as well as emptying by one single assessment for gastric emptying, and
      investigated their association in patients with functional dyspepsia (FD). Next,
      we examined the interaction between the association and abdominal symptoms.
      METHODOLOGY: Sixty-one FD patients according to the Rome III criteria were
      recruited for this study. We measured the radioactive changes of the proximal and
      the whole stomach by the scintigraphy until 120 min, and assessed the reservoir
      function and the respective half-emptying time. We assessed the symptoms by the
      previously validated questionnaires. RESULTS: Disordered emptying was seen in
      55.7% (34/61) of patients, delay in 67.6% (23/34), and acceleration in 32.4%
      (11/34). Impaired reservoir function was found in 49.2% (30/61) of patients,
      which had an association with delayed (p = 0.025) and disordered
      (delay+acceleration) emptying (p = 0.027). Through the period, the radioactive
      decrease was dynamic in the normal, but virtually unchanged in the impaired
      reservoir function group. Symptoms in the motility disordered group tended to be
      more severe than in the normal group. CONCLUSIONS: Gastric reservoir function was
      associated with emptying in FD patients. Abdominal symptoms of FD patients were
      partly derived from the impairment of coordinated gastric motility.

PMID- 18613447
TI  - Nrf2 gene promoter polymorphism and gastric carcinogenesis.
AB  - BACKGROUND/AIMS: Three gene polymorphisms of Nrf2, which regulate the expression
      of detoxifying and antioxidant genes, have been identified. We attempted to
      clarify the relationship of these polymorphisms with the carcinogenesis in the
      stomach. METHODOLOGY: The study was performed in 209 patients with gastric cancer
      and 198 patients with no evidence of gastric malignancies on upper gastroduodenal
      endoscopy. We employed PCR-SSCP method to detect gene polymorphisms. RESULTS:
      Overall, both polymorphisms at position of -686/-684 and -650 were not
      significant risk factors of carcinogenesis in the stomach. However, the -686/-684
      A/G allele carrier had a significantly reduced risk for gastric carcinogenesis (p
      = 0.022), especially of diffuse type (p = 0.020), in H. pylori-negative cases.
      The activity and inflammation scores in Nrf2 -686/-684 A/G carriers were
      significantly lower than those in the non-A/G carriers (p = 0.038 and p = 0.019,
      respectively). CONCLUSIONS: The -686/-684 haplotype of Nrf2 gene may be
      associated with the development of gastric inflammation and with gastric
      carcinogenesis without the influence of H. pylori infection, although overall
      association with gastric carcinogenesis seems to be none.

PMID- 18613448
TI  - Efficacy of prophylactic extended lymphadenectomy with gastrectomy for patients
      with node-negative advanced gastric carcinoma.
AB  - BACKGROUND/AIMS: Extended lymphadenectomy with gastrectomy is widely performed
      for patients with advanced gastric carcinoma. However, the therapeutic value of
      prophylactic extensive lymphadenectomy in patients with node-negative advanced
      gastric cancer is controversial. METHODOLOGY: We retrospectively analyzed 221
      patients who underwent curative gastrectomy for advanced gastric carcinoma
      without lymph node metastasis to evaluate the effect of prophylactic extended
      lymphadenectomy on postoperative survival. The postoperative survival rate of
      patients who underwent extended lymphadenectomy was compared with that of
      patients who underwent limited lymphadenectomy. Predictive risk factors for tumor
      recurrence and recurrent patterns also were analyzed. RESULTS: Extended
      lymphadenectomy improved the postoperative survival rate of patients with
      advanced tumors even when lymph node spread was absent. Whether or not
      prophylactic extended lymphadenectomy was performed significantly affected tumor
      recurrence in patients with node-negative advanced gastric carcinoma.
      CONCLUSIONS: Extensive lymphadenectomy with gastrectomy prolongs survival of
      patients with node-negative advanced tumors.

PMID- 18613449
TI  - Effects of mosapride citrate on patients after vagal nerve, lower esophageal
      sphincter, and pyloric sphincter-preserving nearly total gastrectomy
      reconstructed by jejunal J pouch interposition, and postoperative quality of
      life.
AB  - BACKGROUND/AIMS: Vagal nerve and pylorus-preserving nearly total gastrectomy
      reconstructed by interposition of a jejunal J pouch (hereinafter called NTGP) is
      a function-preserving operation for early gastric cancer. However, some patients
      after NTGP have suffered from postprandial food stasis in the substitute stomach,
      and postprandial stasis leads to abdominal symptoms. To clarify the clinical
      effect of mosapride citrate (hereinafter called MS) for prevention of food stasis
      in the substitute stomach for patients after NTGP, we studied the clinical
      effects of MS before and after administration of MS. METHODOLOGY: In a total of
      24 patients (18 males, 6 females; aged 44-70 years, average 58.1 years) during 5
      years after NTGP for early gastric cancer (D1 lymph node dissection, curability
      A), the relationship between their postoperative quality of life (QOL) and
      emptying function of the substitute stomach (hereinafter called EFS) was compared
      using a radioisotope method before MS therapy and after MS therapy at an oral
      dose of 15mg/day for 3 months. RESULTS: The interviews showd that after MS
      therapy, patients had more evident appetite and ate more food with a slight
      increase in body weight (0.52Kg) compared with patients before MS therapy. Before
      and after MS therapy, patients had no early dumping symtoms, while patients after
      MS therapy clearly had fewer symptoms such as reflux esophagitis, nausea, and
      abdominal pain compared with before MS therapy. After MS therapy, patients also
      had significantly decreased abdominal fullness compared with before MS therapy (p
      = 0.0046). Endoscopically, we found reflux esophagitis in 4 patients before MS
      therapy but in no patients after MS therapy. All patients before MS therapy
      showed residual contents in the substitute stomach, but only 10 patients after MS
      therapy showed residual contents in the substitute stomach. There was a
      significant difference between before and after MS therapy (p = 0.0016).
      Regarding EFS, the time to 50% residual rate before MS therapy (98.7 +/- 13.0
      min) was significantly slower than that after MS therapy (83.2 +/- 13.8 min) (p =
      0.0134). After MS therapy (37.0 +/- 4.9%), the residual rates at 120 minutes were
      significantly decreased compared with patients before MS therapy (44.8 +/- 5.3%)
      (p = 0.0028). Patients after MS therapy clearly had improved stasis of substitute
      stomach compared with before MS therapy. CONCLUSIONS: It was considered that MS
      therapy subsequently improves abdominal fullness due to the postprandial food
      stasis in the substitute stomach, contributing to the improvement of QOL of
      patients after NTGP.

PMID- 18613450
TI  - Clinical experience of endoscopic banding ligation for bleeding gastric varices.
AB  - BACKGROUND/AIMS: Endoscopic variceal ligation is now regarded as the treatment of
      choice for bleeding esophageal varices. However, it is seldom used to treat
      bleeding gastric varices. In this a clinical experience of banding ligation to
      treat bleeding gastric varices is reported. METHODOLOGY: There were 17 male and 5
      female patients with active gastric variceal bleeding who received banding
      ligation. The gastric varices were ligated using pneumoactive ligating devices
      and an attempt was made to ligate all engorged varices at 1 session. After
      endoscopic treatment, intravenous omeprazole 40 mg q12 h was given. RESULTS: An
      average of 2.8 bands were used (1-5 bands) to ligate the gastric varices at 1
      session. All achieved initial hemostasis and there was no immediate complication.
      However, 4 patients (18.2%) developed early rebleeding and it occurred on the
      3rd, 5th, 9th, 14th days after banding ligation respectively. Three of these 4
      patients had Grade III gastric varices. Three (13.6%) patients died within 30
      days. One died of hepatic failure, one of hepatocellular carcinoma and one of
      uncontrolled bleeding. CONCLUSIONS: Variceal ligation is effective for hemostasis
      of bleeding gastric varices. However, early rebleeding is still a problem and
      more often encountered with larger gastric varices.

PMID- 18613452
TI  - Anti-tumor effect of angiogenesis inhibitor TNP-470 and 5-FU combined therapy on
      human gastric cancer xenograft.
AB  - BACKGROUND/AIMS: TNP-470, an angiogenesis inhibitor, has already been used in
      combination with chemotherapy to enhance its antitumor activity. The mechanism of
      enhanced antitumor activity in combination therapy has not been clarified,
      however, and few studies have described the combined effect of TNP-470 and 5
      fluorouracil (5-FU) on gastric cancer. The present study was conducted to
      investigate the effect of TNP-470 + 5-FU on gastric cancer cell line MKN-45 in
      vivo and in vitro. METHODOLOGY: MKN-45 cells were subcutaneously injected into
      mice that were divided into 4 groups: a control group, a 5-FU treated group, a
      TNP-470 treated group, and a 5-FU + TNP-470 treated group. After the inoculation,
      the volume of subcutaneous tumors was measured. Blood and lymphatic vessels were
      also analyzed for the assessment of lymphangiogenesis. RESULTS: Compared with 5
      FU or TNP-470 alone, the combined effect of TNP-470 and 5-FU significantly
      inhibited and suppressed tumor growth in a synergistic fashion. The combined
      therapy significantly suppressed both angiogenesis and lymphagenesis.
      CONCLUSIONS: The study suggests that the combined therapy provides an enhanced
      antitumor effect on human gastric cancer. The enhanced antitumor activity is
      explained mainly by the stronger inhibition of angiogenesis.

PMID- 18613451
TI  - Chemiluminescence assay of mucosal reactive oxygen species in gastric cancer,
      ulcer and antral mucosa.
AB  - BACKGROUND/AIMS: Reactive oxygen species (ROS) have been implicated in
      inflammatory and cancerous illness, including that of the gastrointestinal tract.
      The oxidative damage incurred during human gastric ulcer or cancer mucosa may be
      related to acumination of ROS. In this study, we aimed to demonstrate oxidative
      stress of gastric ulcer and cancer mucosa compared to gastric antral mucosa.
      METHODOLOGY:  PATIENTS: Thirty-four patients with gastric ulcer and gastric
      cancer were enrolled in this study. Gastric mucosa specimens, taken from upper GI
      endoscopic biopsy, from the lesion (ulcer or cancer) and antrum were sent for the
      activity of O2- or H2O2 determined by chemiluminescence assay. Protein
      concentrations in the tissue homogenates were determined by Bio-Red protein
      assay. The production of O2- or H2O2 per unit of protein was calculated by
      dividing the tissue CL level by the protein content of a tissue. RESULTS: The
      oxidative stress metabolites O2- and H2O2 of mucosa were evaluated by
      chemiluminescence assay in gastric lesions (27 ulcers and 7 cancers) and gastric
      antrum. Gastric lesion showed significantly increased O2- than antral mucosa
      (18.77 +/- 45.18 (counts/sec x microg), 95% CI 3.01, 34.53 vs. 3.58 +/- 6.89
      (counts/sec x microg), 95% CI 1.18, 5.98, p < 0.05). There was also significantly
      greater expression of H2O2 in gastric lesion than gastric antral mucosa (76.06 +/
      148.36 (counts/sec x microg), 95% CI 24.30, 127.83 vs. 912.41 +/- 20.22
      (counts/sec x microg), 95% CI 5.35, 19.46, p = 0.008). Differences of mucosal O2-
      and H2O2 between gastric ulcer and cancer were not significant. There was
      significant correlation of O2- and H2O2 generation in gastric lesion mucosa.
      CONCLUSIONS: Oxidative stress is now thought to make a significant contribution
      to inflammatory disease and malignancy. The reason that overproduction of free
      radicals is a feature of such a broad spectrum of diseases derived from the fact
      that oxidative metabolism is a necessary part of every cell's metabolism. In this
      study, we demonstrated increased ROS production in gastric ulceration and cancer
      compared with gastric antral mucosa.

PMID- 18613453
TI  - Time-dependent relevance of prognostic factors in patients with gastric cancer.
AB  - BACKGROUND/AIMS: Prognostic factors are useful for establishing a prognosis of
      patients from the time of operation. However, the value of individual prognostic
      factors may change dependent on the length of the follow-up period, and it is not
      clear how long these factors keep their prognostic relevance. METHODOLOGY: Data
      was used from 233 Japanese patients treated by potentially curative resection for
      primary gastric cancer, between 1993 and 1998. Survival analysis was done
      starting at 1-yearly intervals after operation and follow-up in the first
      analysis started at the time of the operation. RESULTS: Prognostic relevance of
      tumor size was not evident for total follow-up time but was significantly
      emphasized 1 year after operation. Serosal invasion lost its prognostic value
      within one year of operation. The status of lymph node metastases retained its
      ability to predict survival after 2 years' follow-up whereas after 3 years'
      follow-up nodal status seemed to be without significance. CONCLUSIONS: A distinct
      time-dependency with varied patterns was found in the influence of some
      prognostic factors on survival. Detecting the changing importance of prognostic
      factors could provide new biological insights that might otherwise be missed, and
      may help determine the most appropriate clinical use of various factors.

PMID- 18613454
TI  - Is PET-CT suitable for predicting lymph node status for gastric cancer?
AB  - BACKGROUND/AIMS: To verify the value of PET-CT for predicting lymph node status
      of gastric cancer preoperatively. METHODOLOGY: 78 gastric cancer patients
      accepted PET-CT preoperatively, the results of lymph node status were compared
      with the postoperative pathology. CT was used as control. RESULTS: The accuracy
      of PET-CT and CT in N category was 55.1% vs. 54.4%, respectively. The
      sensitivity, specificity, accuracy, positive predicting value (PPV), and negative
      predicting value (NPV) of PET-CT in predicting position of positive lymph node
      were 31.0%, 97.2%, 61.5%, 92.9%, and 54.7%, respectively. While for CT, were
      60.5%, 83.3%, 70.6%, 82.1%, and 62.5%, respectively. For tier 1 lymph node
      metastasis, the sensitivity, specificity, accuracy, PPV, and NPV of PET-CT were
      31.6%, 95.0%, 64.1%, 85.7%, and 59.4%, respectively. While for CT, were 60.0%,
      78.8%, 69.1%, 75.0%, and 65.0%, respectively. The sensitivity of CT was
      significantly better (p = 0.031). For tier 2 or tier 3 lymph node metastasis, the
      sensitivity, specificity, accuracy, PPV, and NPV of PET-CT were 12.0%, 98.1%,
      70.5%, 75.0%, and 70.3%, respectively. While for CT, were 22.7%, 93.5%, 70.6%,
      62.5%, and 71.7%, respectively, without significance. CONCLUSIONS: PET-CT is not
      sensitive enough to predict the regional lymph node status of gastric cancer
      preoperatively.

PMID- 18613455
TI  - A study of the relationship between Helicobacter pylori microbial susceptibility,
      13C-urea breath test values.
AB  - BACKGROUND/AIMS: Diagnostic methods for Helicobacter pylori (H. pylori) infection
      can be divided into invasive endoscopic methods and non-invasive methods. A
      typical and widely used non-invasive method is the 13C urea breath test (UBT). In
      this study, the possibility of a correlation between pre-treatment UBT values
      with H. pylori antimicrobial resistance is investigated. METHODOLOGY: The
      subjects were 119 consecutive patients who attended this hospital for H. pylori
      testing. Average age was 47.5 +/- 13.2 years, with a male:female ratio of 2.05:1.
      The diagnosis was gastric ulcer in 43 subjects, duodenal ulcer in 27,
      gastroduodenal ulcer in 21 and chronic gastritis in 28. Subjects underwent UBT as
      well as upper gastrointestinal endoscopy (UGITE). The diagnosis of H. pylori
      infection was examined by the results of culture, histological examination and
      the rapid urease test (RUT). The mean inhibitory concentration (MIC) was
      determined for each antimicrobial agent in the bacterial isolates that could be
      cultured. RESULTS: In this study, the sensitivity and specificity were excellent
      at 97.0% and 100% with a cut-off point of 3.5 per thousand for UBT respectively.
      Clarithromycin resistance was more common in the group with high UBT values. No
      correlation at all was seen between UBT values and metronidazole, sparafloxacin,
      cefaclor and amoxicillin susceptibility. CONCLUSIONS: It is possible that UBT
      values also tend to be higher in cases of CAM resistance.

PMID- 18613456
TI  - Clinicopathology and prognosis of mucinous gastric carcinoma.
AB  - BACKGROUND/AIMS: Mucinous gastric carcinoma (MGC) is a rare histopathological
      type of gastric carcinoma, for which the clinicopathological features and
      prognosis remain controversial. To clarify the clinical significance of mucinous
      histological type in gastric cancer, we studied clinicopathological
      characteristics of MGC tumors and prognosis of patients. METHODOLOGY: Forty-one
      patients with MGC and 1,407 patients with non-mucinous gastric carcinoma (NGC)
      were included in the study. Tumors were evaluated against patient gender and age,
      tumor location, size, and macroscopic type, depth of gastric wall invasion, lymph
      node metastasis, liver metastasis, peritoneal dissemination, distant metastasis,
      stage, and operative curability. RESULTS: Compared with NGC tumors, MGC tumors
      were larger, showed more serosal invasion, were associated with a higher
      incidence of lymph node metastasis, and peritoneal dissemination, and tended to
      be at a more advanced stage. However, multivariate analysis demonstrated that the
      mucinous histological type was neither an independent prognostic factor nor an
      independent risk factor for lymph node metastasis in patients with gastric
      cancer. CONCLUSIONS: The mucinous histological type had no influence on patient
      outcome or the frequency of lymph node metastasis. MGC tumors are therefore
      biologically similar to those in NGC.

PMID- 18613457
TI  - Evaluation of calorie intake according to age and sex in patients undergoing
      surgery for gastric cancer.
AB  - BACKGROUND/AIMS: We studied food intake in 107 patients undergoing gastric
      surgery, with emphasis on postoperative quality of life (QOL). The time course of
      food intake after surgery, sex- and age-related differences in food intake, and
      the relation of food intake to surgical procedure were evaluated retrospectively.
      METHODOLOGY: The following variables were studied: 1) the time required for
      stabilization of food intake, assessed on the basis of the time course of food
      intake after operation; 2) the relations of sex and age to postoperative food
      intake, assessed by comparing food intake according to sex and age; and 3)
      postoperative food intake according to surgical procedure, evaluated by
      calculating the ratio of postoperative food intake to the food intake of healthy
      individuals matched for sex and age. RESULTS: At 6, 12, and 24 months after
      operation, there was no difference in food intake among the three operative
      procedures; food intake was stable from 6 months onward. When food intake was
      analyzed according to age, similar trends were seen in men and women, and there
      were no significant differences in food intake among patients in their 40s, 50s,
      or 60s. Food intake was significantly lower in patients in their 70s than in
      patients in the other age groups. Food intake even in women with significantly
      decreased food intake or in patients 70 years or older was not necessarily low as
      compared with food intake levels in healthy individuals. CONCLUSIONS: Food intake
      is substantially affected by the period of time after surgery, as well as by sex,
      and age at the time of surgery.

PMID- 18613458
TI  - Effect of perioperative parenteral nutritional support for gastric cancer
      patients undergoing gastrectomy.
AB  - BACKGROUND/AIMS: Malnutrition is frequently seen in gastric cancer patients.
      Perioperative nutritional support may reduce postoperative complications,
      especially in severely depleted gastric cancer patients with GI obstruction.
      However, the beneficial effects of perioperative total parenteral nutrition for
      gastric cancer surgery patients still have not been clearly demonstrated in
      Taiwan. This study evaluated the effects of perioperative nutritional support for
      severely malnourished patients with gastric cancer undergoing gastrectomy.
      METHODOLOGY: The study analyzed malnourished patients with gastric cancer who
      underwent gastrectomy from Oct 2000 to Oct 2002. Total nutritional support was
      examined for severely depleted patients with body weight loss > 10% over 6 months
      or a low serum albumin level (< 3.0g/dL). These patients were classified into two
      groups, those without TPN (total parenteral nutrition) use and those with TPN
      use. The patients who received TPN were further divided into 2 groups, those who
      received TPN postoperatively and those who received it perioperatively.
      Correlation with the postoperative outcome was then made. RESULTS: Forty patients
      who underwent total gastrectomy and 78 patients who underwent subtotal
      gastrectomy had severe malnutrition preoperatively. We found gastric cancer
      patients with malnutrition had high morbidity and mortality rates (29.7% and
      8.6%, respectively) when undergoing gastrectomy, especially total gastrectomy.
      There was a higher morbidity rate in the group without TPN (66.7% vs. 16% and
      43.75% vs. 21.74%) in both the subtotal and total gastrectomy groups, and a
      longer postoperative stay for patients without TPN (35.21 +/- 25.05 vs. 21.32 +/-
      12.32) in the total gastrectomy group than for patients with TPN in these groups.
      The mortality rate, morbidity rate and postoperative stay were higher in patients
      who received postoperative TPN only than in patients with peri-operative TPN.
      CONCLUSIONS: TPN use, perioperatively or postoperatively, can help reduce the
      morbidity and mortality of these patients. Total nutritional support is effective
      for patients with malnutrition undergoing gastric cancer surgery.

PMID- 18613459
TI  - Postoperative weight loss during hospital stays in patients with gastric cancer
      undergoing surgical resection.
AB  - BACKGROUND/AIMS: The timing of sampling weight loss in the patients with gastric
      cancer undergoing surgical resection can be divided into 2 categories: prior to
      operation and postoperative follow-up as an outpatient. In this study, a third
      timing is proposed; the postoperative period during hospital stay. The purposes
      of this report were to identify the clinical variables related to postoperative
      weight loss during the hospital stay in gastric cancer patients and to
      investigate the influence of the weight loss on the long-term survival.
      METHODOLOGY: Records of 313 patients who underwent gastrectomies for cancer
      between 1992 and 2003 were reviewed retrospectively. Patients were divided into 2
      groups according to the median value of the rate of weight loss. Overall survival
      was estimated by the Kaplan-Meier Method. RESULTS: The postoperative hospital
      stays were significantly longer in the serious weight loss group than in the mild
      weight loss group. Developing complication, extended lymph node dissection, and
      operation time had the impact independently of the rate of weight loss. The
      overall survival was not different between the serious weight loss and the mild
      weight loss groups by a log-rank test (5-year survival, 70.1% vs. 70.5%, p =
      0.82). CONCLUSIONS: Although the serious weight loss during hospital stay means
      the true surgical damage in gastric cancer patients, it has no influence on the
      long-term survival.

PMID- 18613460
TI  - Anti Helicobacter pylori IgG and IgA response in patients with gastric cancer and
      chronic gastritis.
AB  - BACKGROUND/AIMS: Immune response against Helicobacter pylori is important for the
      course and outcome of infection. We conducted study looking for the difference in
      anti H. pylori IgG and IgA between patients with intestinal type of gastric
      cancer, superficial and atrophic gastritis. METHODOLOGY: For this study, 133
      patients infected with H. pylori were enrolled: 50 with superficial gastritis, 42
      with atrophic gastritis and 41 with gastric cancer. Anti H. pylori IgG and IgA
      ELISA tests were performed. The difference in antibody titers of IgG and IgA,
      frequency of IgA > IgG ratio and combination of low IgG and IgA > IgG ratio were
      analyzed. RESULTS: The patients with gastritis had higher titer of IgG that the
      patients with gastric cancer (p < 0.01). The patients with superficial gastritis
      had higher titer of IgA than the patients with gastric cancer (p < 0.05). IgA >
      IgG ratio is more frequent in patients with gastric cancer than in the patients
      with superficial gastritis (p < 0.01). Low IgG and IgA > IgG is more frequent in
      the patients with gastric cancer than in the patients with gastritis (p < 0.01).
      CONCLUSIONS: The patients with gastric cancer elicit different anti H. pylori IgG
      and IgA response than the patients with superficial and atrophic gastritis. Low
      IgG and IgA predominance seems characteristic for gastric cancer.

PMID- 18613461
TI  - Laparoscopic subtotal gastrectomy for gastric carcinoma treatment.
AB  - Laparoscopic surgery of the stomach is not well accepted in patients with
      malignant disease. This paper shows the first experiences with this procedure at
      the Clinical Hospital and Medical School, Split, in two patients with early stage
      gastric carcinoma. The first patient was a 57 year old man who had had some
      gastric symptoms for a while. The other patient was a 73 year old man who had
      ulcer disease 52 years ago. Laparoscopic subtotal gastrectomy with omentectomy
      and Roux-en-Y reconstruction of the alimentary tract was performed on both
      patients. Pathohystological analysis of the resected part of the stomach showed
      the early stage gastric adenocarcinoma without metastases to the lymph nodes
      around the stomach or any pathological changes in the omentum for both of the
      patients. There were no complications during postoperative period. The first
      patient was released from the hospital after 8 and other after 9 days. All
      oncological principles were satisfied with laparoscopic subtotal resection with
      good and fast postoperative recovery without complications.

PMID- 18613462
TI  - [Including events in childhood].

PMID- 18613464
TI  - ["What kind of health do you need?"].

PMID- 18613463
TI  - [Children must be heard, supported and strengthened].

PMID- 18613465
TI  - [How do I say that it is my child?].

PMID- 18613466
TI  - [Heightened patient knowledge leads to better outcomes].

PMID- 18613467
TI  - [Permanent improvement in care and investigation].

PMID- 18613468
TI  - [Studies enhance evidence and knowledge].

PMID- 18613469
TI  - [Operation clinical-competence].

PMID- 18613470
TI  - [Anxiety about falls].

PMID- 18613471
TI  - ["Swiss nurses should not become political"].

PMID- 18613472
TI  - [Parents who are too weak].

PMID- 18613473
TI  - ["Dad has really been strange for some time"].

PMID- 18613474
TI  - [An everyday action of prevention].

PMID- 18613475
TI  - [Awareness of night].

PMID- 18613476
TI  - [Implantable infusion systems: precautions and advantages].

PMID- 18613477
TI  - [World cultures: distribution and discovery].

PMID- 18613478
TI  - ["Disease does not make you lose family duties, espcially if you are a parent"].

PMID- 18613479
TI  - [What I really want to say].

PMID- 18613480
TI  - Changing educational inequalities in India in the context of affirmative action.
AB  - Indian society suffers from substantial inequalities in education, employment,
      and income based on caste and ethnicity. Compensatory or positive discrimination
      policies reserve 15% of the seats in institutions of higher education and state
      and central government jobs for people of the lowest caste, the Scheduled Caste;
      7.5% of the seats are reserved for the Scheduled Tribe. These programs have been
      strengthened by improved enforcement and increased funding in the 1990s. This
      positive discrimination has also generated popular backlash and on-the-ground
      sabotage of the programs. This paper examines the changes in educational
      attainment between various social groups for a period of nearly 20 years to see
      whether educational inequalities have declined over time. We use data from a
      large national sample survey of over 100,000 households for each of the four
      survey years--1983, 1987-1988, 1993-1994, and 1999-2000--and focus on the
      educational attainment of children and young adults aged 6-29. Our results show a
      declining gap between dalits, adivasis, and others in the odds of completing
      primary school. Such improvement is not seen for Muslims, a minority group that
      does not benefit from affirmative action. We find little improvement in
      inequality at the college level. Further, we do not find evidence that upper
      income groups, the so-called creamy layer of dalits and adivasis,
      disproportionately benefit from the affirmative action programs at the expense of
      their lower-income counterparts.

PMID- 18613481
TI  - An assessment of China's fertility level using the variable-r method.
AB  - The fertility level in China is a matter of uncertainty and controversy. This
      paper applies Preston and Coale's (1982) variable-r method to assess the
      fertility level in China. By using data from China's 1990 and 2000 censuses as
      well as annual population change surveys, the variable-r method confirms that
      Chinese fertility has reached a level well below replacement.

PMID- 18613482
TI  - The legacies of context: past and present influences on contraceptive choice in
      Nang Rong, Thailand.
AB  - This study explores the ways in which women's contraceptive behavior in a rural
      area of Thailand is shaped by both past and present context, based on the life
      course framework. Although the importance of contextual influences for
      contraceptive behavior is well established in the literature, relatively little
      research has been conducted that explores how behavior is influenced by
      historical and contemporaneous contextual factors and by individual life
      experiences. In addition, much of this research has neglected the role of the
      normative environment within which contraceptive use takes place. The focus of
      this paper centers on the effect of contraceptive environment at both early and
      late stages of the life course and on how this effect is shaped by individual
      experience with migration to urban areas. This study takes advantage of a unique,
      prospective longitudinal data set with detailed information on community context
      at multiple points in time, an important improvement upon prior research. The
      results show that contraceptive behavior is particularly responsive to current
      community context, with past context primarily exerting an indirect effect on
      behavior through shaping current contextual influences.

PMID- 18613483
TI  - The gradient in sub-Saharan Africa: socioeconomic status and HIV/AIDS.
AB  - Using data from the Demographic and Health Surveys (DHS) for Burkina Faso (2003),
      Cameroon (2004), Ghana (2003), Kenya (2003), and Tanzania (2003), I investigate
      the cross-sectional relationship between HIV status and socioeconomic status. I
      find evidence of a robust positive education gradient in HIV infection, showing
      that, up to very high levels of education, better-educated respondents are more
      likely to be HIV-positive. Adults with six years of schooling are as much as
      three percentage points more likely to be infected with HIV than adults with no
      schooling. This gradient is not an artifact of age, sector of residence, or
      region of residence. With controls for sex, age, sector of residence, and region
      of residence, adults with six years of schooling are as much as 50% more likely
      to be infected with HIV than those with no schooling. Education is positively
      related to certain risk factors for HIV including the likelihood of having
      premarital sex. Estimates of the wealth gradient in HIV, by contrast, vary
      substantially across countries and are sensitive to the choice of measure of
      wealth.

PMID- 18613484
TI  - Macroeconomic fluctuations and mortality in postwar Japan.
AB  - Recent research has shown that after long-term declining trends are excluded,
      mortality rates in industrial countries tend to rise in economic expansions and
      fall in economic recessions. In the present work, co-movements between economic
      fluctuations and mortality changes in postwar Japan are investigated by analyzing
      time series of mortality rates and eight economic indicators. To eliminate
      spurious associations attributable to trends, series are detrended either via
      Hodrick-Prescott filtering or through differencing. As previously found in other
      industrial economies, general mortality and age-specific death rates in Japan
      tend to increase in expansions and drop in recessions, for both males and
      females. The effect, which is slightly stronger for males, is particularly
      noticeable in those aged 45-64. Deaths attributed to heart disease, pneumonia,
      accidents, liver disease, and senility--making up about 41% of total mortality-
      tend to fluctuate procyclically, increasing in expansions. Suicides, as well as
      deaths attributable to diabetes and hypertensive disease, make up about 4% of
      total mortality and fluctuate countercyclically, increasing in recessions. Deaths
      attributed to other causes, making up about half of total deaths, don't show a
      clearly defined relationship with the fluctuations of the economy.

PMID- 18613485
TI  - Fertility in New York State in the pre-Civil War era.
AB  - Knowledge is quite limited about the extent and social correlates of marital
      fertility decline for the United States in the early part of the nineteenth
      century. Manuscripts from the New York State census of 1865 indicate a very slow
      decline in marital fertility during the initial decades of the nineteenth century
      and more rapid decline as the Civil War approached. Little evidence of fertility
      control within marriage is found for the very oldest women in the sample, but
      analysis of parity progression ratios indicates that some control had emerged by
      the midpoint of the nineteenth century. Fertility decline was most evident in the
      urban, more economically developed areas, but our data also indicate that the
      limited availability of agricultural land may have affected the transition. While
      a marital fertility transition occurred in nineteenth-century New York, many
      couples in various geographic areas and social strata continued to have quite
      high levels of fertility, indicating difficulties that were probably faced in
      controlling reproduction.

PMID- 18613486
TI  - Population change and farm dependence: temporal and spatial variation in the U.S.
      Great Plains, 1900-2000.
AB  - I investigate the relationship between county population change and farm
      dependence in the Great Plains region during the twentieth century, using spatial
      data analysis techniques. This research is rooted in a long-standing sociological
      and demographic interest in population responses to economic transitions and
      informs the theoretical understanding of urbanization processes. Using census and
      environmental data, the analysis challenges earlier assertions of a simple
      transition in the relationship between farm dependence and population change that
      accompanied modern technological advancements, namely tractors (the mechanization
      thesis). Rather than observing the proposed positive-to-negative shift, study
      results show a negative association throughout the pre- and post-mechanization
      periods. Partial support is found if the thesis is revised to consider the
      relationship between population change and the change in farm dependence rather
      than the level of farm dependence. Findings show mixed support for an alternative
      argument that nonfarm industries moderate the influence of farm dependence (the
      industry complex thesis). In contrast to earlier applications of the thesis,
      industrial relations in the Great Plains context are characterized by
      specialization rather than cooperation.

PMID- 18613487
TI  - Trends in U.S. adult chronic disease mortality, 1960-1999: age, period, and
      cohort variations.
AB  - In this paper, I examine temporal changes in U.S. adult mortality by chronic
      disease cause of death and by sex over a 40-year period in the second half of the
      twentieth century. I apply age-period-cohort (APC) analyses that combine
      conventional approaches and a new method of model estimation to simultaneously
      account for age, period, and cohort variations in mortality rates for four
      leading causes of deaths, including heart disease, stroke, lung cancer, and
      breast cancer. The results show that large reductions in mortality since the late
      1960s continued well into the late 1990s and that these reductions were
      predominately contributed by cohort effects. Cohort effects are found to differ
      by specific causes of death examined, but they generally show substantial
      survival improvements. Implications of these results are discussed with regard to
      demographic theories of mortality reductions, differential cohort accumulation of
      health capital and lifetime exposures to socioeconomic and behavioral risk
      factors, and period changes in diagnostic techniques and medical treatment.

PMID- 18613488
TI  - Marital strategies for regulating exposure to HIV.
AB  - In a setting where the transmission of HIV occurs primarily through heterosexual
      contact and where no cure or vaccine is available, behavioral change is
      imperative for containing the epidemic. Abstinence, faithfulness, and condom use
      most often receive attention in this regard. In contrast, this article treats
      marriage as a resource for HIV risk management via mechanisms of positive
      selection (partner choice) and negative selection (divorce of an adulterous
      spouse). Retrospective marriage histories and panel data provide the evidence for
      this study and results indicate that men and women in Malawi increasingly turned
      to union-based risk-avoidance strategies during the period that the threat of
      HIV/AIDS materialized. Although both sexes strategize in a similar fashion, men
      are better equipped than women to deploy these strategies to their advantage. The
      article concludes with reflections on the long-term and population-level
      implications of these coping mechanisms.

PMID- 18613489
TI  - Risk preferences and the timing of marriage and childbearing.
AB  - The existing literature on marriage and fertility decisions pays little attention
      to the roles played by risk preferences and uncertainty. However given
      uncertainty regarding the availability of suitable marriage partners, the ability
      to contracept, and the ability to conceive, women's risk preferences might be
      expected to play an important role in marriage and fertility timing decisions. By
      using data from the Panel Study of Income Dynamics (PSID), I find that measured
      risk preferences have a significant effect on the timing of both marriage and
      fertility. Highly risk-tolerant women are more likely to delay marriage,
      consistent with either a search model of marriage or a risk-pooling explanation.
      In addition, risk preferences affect fertility timing in a way that differs by
      marital status and education, and that varies over the life cycle. Greater
      tolerance for risk leads to earlier births at young ages, consistent with these
      women being less likely to contracept effectively. In addition, as the subgroup
      of college-educated, unmarried women nears the end of their fertile periods,
      highly risk-tolerant women are likely to delay childbearing relative to their
      more risk-averse counterparts and are therefore less likely to become mothers.
      These findings may have broader implications for both individual and societal
      well-being.

PMID- 18613491
TI  - [Progress about the research of atmospheric persistent organic pollutants in
      remote areas].
AB  - Recently, atmospheric distribution, transport, and reaction of persistent organic
      pollutants (POPs) in remote areas are getting more attention. Based on the
      passive air sampler, the networks are established for studying the temporal and
      spatial distribution of atmospheric POPs in remote areas. The results suggest
      that the atmospheric concentrations of POPs display a peak value in the 1980s. As
      the use of POPs has been forbidden after 1980s, concentrations of POPs in air are
      generally reduced. Concentration of POPs in atmosphere is influenced by
      temperature and seasonal usage. High concentration of organochlorine pesticides
      is observed in summer and the comparatively low level is detected in winter. For
      PAHs, the trend is contrary. High volatility and long-range transport of POPs
      lead to the global distribution of POPs and accumulation of POPs in remote areas.
      High mountain is the "acceptor" of atmospheric POPs and cold condensation plays
      the main role in capturing POPs in high elevation areas. Distribution, transport,
      exchange direction and exchange flux of POPs among air/water, air/soil, air/snow
      and air/vegetation interfaces are mainly controlled by temperature, precipitation
      and characteristics of POPs. Models were developed on the basis of the effect of
      these factors. Taken together the transport model and source analysis of POPs,
      transport mechanism of POPs seems to be clearer. This paper reviewed the progress
      about the above-mentioned scientific topics and discussed the deficiencies of
      current researches. Furthermore, it pointed out the further work needed for the
      study of atmospheric POPs in remote areas.

PMID- 18613490
TI  - Coparenting and nonresident fathers' involvement with young children after a
      nonmarital birth.
AB  - We use data from the Fragile Families and Child Wellbeing Study to investigate
      the association between coparenting quality and nonresident fathers' involvement
      with children over the first five years after a nonmarital birth. We find that
      about one year after a nonmarital birth, 48% of fathers are living away from
      their child, rising to 56% and then to 63% at three and five years, respectively
      Using structural equation models to estimate cross-lagged effects, we find that
      positive coparenting is a strong predictor of nonresident fathers' future
      involvement, whereas fathers' involvement is only a weak (but significant)
      predictor of future coparenting quality. The positive effect of coparenting
      quality on fathers' involvement is robust across several techniques designed to
      address unobserved heterogeneity and across different strategies for handling
      missing data. We conclude that parents' ability to work together in rearing their
      common child across households helps keep nonresident fathers connected to their
      children and that programs aimed at improving parents' ability to communicate may
      have benefits for children irrespective of whether the parents' romantic
      relationship remains intact.

PMID- 18613492
TI  - [Application research of data assimilation in air pollution numerical
      prediction].
AB  - Based on an air pollution modeling system coupling with the non-hydrostatic fifth
      generation mesoscale meteorological model (MM5) and the regional modeling system
      for aerosols and deposition (REMSAD), the forecast results of NOx and SO2 in
      August and September 2002 in Nanjing were assimilated with the optimal
      interpolation method and the ensemble Kalman filter. The results show that the
      improvement rates of deviation mean value of NOx and SO2 after assimilated with
      the optimal interpolation method are 34.20% and 47.53%, and the improvement rates
      of root mean square errors are 31.95% and 42.04% respectively. It is also
      demonstrated that the improvement rates of deviation mean value of NOx and SO2
      after assimilated with the ensemble Kalman filter with 30 ensemble members are
      26.73% and 60.75%, and the improvement rates of root mean square errors are
      25.20% and 55.16% respectively. So, the optimal interpolation method and the
      ensemble Kalman filter both can improve the quality of the initial state from the
      air pollution numerical prediction model. The comparative experiments on the
      assimilation performance with the optimal interpolation method and the ensemble
      Kalman filter with 61 ensemble members were performed, and the experiments
      demonstrate that the assimilation performance of the ensemble Kalman filter with
      61 ensemble members were improved compared with 30 ensemble members, and with the
      increase of the ensemble members, the improvement to the initial state of NOx and
      SO2 with the ensemble Kalman filter will be better than the optimal interpolation
      method.

PMID- 18613493
TI  - [Validation of a prediction method for indoor air pollution].
AB  - The validation study of the prediction method for indoor air pollution was
      carried out by comparing the results of emission models based on data obtained in
      a large and a small emission chamber, with actual measured concentrations. A new
      decorated room was studied as a case. Emissions of complicated objects and simple
      surface layer materials were studied respectively in the large and small chamber
      and emission models were developed. Those models were based on the assumptions
      regarding mass conservation of substances and the hypothesis that pollutants were
      well mixed. The emissions of formaldehyde and TVOC (total volatile organic
      compounds) in the studied room were predicted by the method. The predicted
      concentration trend of pollutants was in accordance with the measured trend when
      some air exchange (0.03 ACH, air change per hour) was taken into account. The
      normalized standard errors of formaldehyde and TVOC pollution prediction were
      respectively 2.8% and 1.6%. Modeling analysis shows that the contribution to
      total formaldehyde pollution of the studied room was: furniture > paint > floor;
      the contribution to total TVOC pollution was: paint > floor > furniture. The
      results lead to the conclusion that this prediction method can well describe the
      pollution trend, can assess the contribution of different sources, can guide the
      choice of building materials and is an effective tool for indoor air pollution
      assessment and control.

PMID- 18613494
TI  - [Seasonal variation of total gaseous mercury in Changbai Mountain area].
AB  - An intensive field campaign monitoring was conducted from August 2005 to July
      2006 using the automatic atmospheric mercury analyzers for one year' s
      measurement of total gaseous mercury (TGM) in Changbai Mountain area. Results
      show the mean concentration of TGM is (3.22 +/- 1.78) ng x m(-3) and it presents
      seasonal variation as followings: winter > spring > autumn > summer. Given the
      background concentration of atmospheric mercury in the Northern Hemisphere,
      mercury concentrations are totally elevated in Changbai Mountain area. The
      regional source of mercury in the atmosphere seems to be anthropogenic Hg
      emissions mainly due to local biofuel use and coal combustion from industry and
      domestic uses. The potential mercury source may be regional mercury emissions
      from soil and the long distance transportation of mercury in the atmosphere.

PMID- 18613495
TI  - [Effects of elevated O3 on the volatile organic compounds emit from Ginkgo biloba
      and Pinus tabulaeformis].
AB  - To study the impact of elevated tropospheric O3 concentrations on BVOCs emissions
      by Pinus tabulaeformis and Ginkgo biloba in urban area, the trees were exposed in
      open-top chambers. Two ozone treatments were established: ambient air
      (approximately 30 nmol x mol(-1) ) (CK) and elevated O3 concentrations (80 nmol x
      mol(-1) ) (O3 ). Elevated O3 concentrations significantly induced isoprene to
      emit for Pinus tabulaeformis and Ginkgo biloba (p < 0.05), and delta3-carene for
      Ginkgo biloba (p < 0.05). The emission rates were increased to 1.96, 9.71 and
      0.09 microg/(g x h) (-1), respectively. There were no significant differences
      between ozone fumigation treatments for the other monoterpenes. At the same time,
      the relative abundances of the monoterpenes and isoprene were to be different
      between tree species and effect by O3 exposure. In CK chambers, the dominate
      BVOCs emitted by Ginkgo biloba was isoprene, and a-pinene for Pinus
      tabulaeformis. In the elevated O3 chambers, the isoprene accounted for 64.73% of
      Pinus tabulaeformis BVOCs. To sum up, the BVOCs emitting patterns were influenced
      by elevated O3 significantly.

PMID- 18613496
TI  - [Concentrations and size distributions of water soluble ions of atmospheric
      aerosol at the summit of mount Tai].
AB  - In order to research on the air pollutants' long-range transportation in North
      China, aerosol samples were collected with Andersen cascade sampler at the summit
      of mount Tai during June 2006, in Shandong Province. The water soluble ionic
      concentrations were analyzed by IC. It shows that there are three types of size
      distribution: 1) ions whose mass resided mainly within the accumulation mode with
      the peak at 0.43-0.65 microm (SO4(2-), NH4+, K+); 2) Ions whose mass resided
      mainly within coarse particles with the peak at 4.7-5.8 microm (Ca2+, Mg2+); 3)
      Ions which were two modes with the peak at 0.43-0.65 microm and 4.7-5.8 microm
      (NO3-, NO3-,Cl-). The mass median diameter of SO4(2-) with high concentration is
      between 0.5 microm and 0.8 microm, and belongs to the "drop mode". The
      concentration of ions such as SO4(2-), NO3-, NH4+ and K+ has a huge variety and
      the sulfate has the most great variety with the lowest concentration which is 4.0
      microg x m(-3) and the highest concentration which is 42.3 microg x m(-3). The
      ions (SO4(2-), NO3-, NH4+) reach the high value when the humid air mass comes
      from the south.

PMID- 18613497
TI  - [Analysis of phosphorus distribution characters and their sources of the major
      input rivers of Three Gorges Reservoir].
AB  - The seasonal characters of the water flux and suspended substance, phosphorus in
      the water of input rivers of Three Gorges Reservoir (TGR) were discussed, and the
      their distributions among three major input rivers (Changjiang river,
      Jialingjiang river and Wujiang river) were studied, according to the survey
      conducted from Jan. 2004 to Dec. 2005. The results indicate that those
      parameters' seasonal changes are obvious. The flux and suspended substance in
      abundant water period are more higher than them in low water period, which
      displays suspended substance origins from bedload and that the water and soil
      severely lose in drainage areas of three input rivers. In the three monitor
      sections of input rivers of TGR, the average contents per year of total
      phosphorus are about 0.12-0.29 mg/L, which exceeds the 1970s level of the three
      input rivers. Most of total phosphate is total solid phosphate (TPP) exceeding
      75% of them. TP and TPP have both distinct positive correlation with the flux and
      suspended substance in water of input rivers of TGR, and TPP and TP have also the
      same correlation, which means that phosphate pollution in the input rivers of TGR
      comes from bedload. The nonpoint source pollution has had far-reaching influence
      upon phosphate pollution. Nitrogen and phosphate are not the major limiting
      factor of the nutritious salts in the input rivers of TGR. The rate of between
      nitrogen and phosphate (N/P) is in higher level (above 30), that is phosphate
      first will reach lower level and maybe become the limiting factor of the
      nutritious salts in the input rivers of TGR.

PMID- 18613498
TI  - [Seasonal water quality changes in the Huoditang forest region of the Qinling
      Mountain range].
AB  - This study was conducted in the Huoditang forest region of Shaanxi Province. The
      region is located in the Qinling Mountain range. We collected stream water
      samples at the outlets of two small watersheds and two tributaries each month
      across an eight year period. The samples were analyzed for pH and water
      chemistry. Changes in pH and water chemistry with season were studied by using
      contributing factor analyses. The results of the study showed that stream water
      was slightly alkaline, with the pH ranging from 7.1 to 8.4 throughout the year.
      Stream water pH was higher in winter and spring and lower in summer and autumn.
      The NO3- concentrations in stream water were highest in spring and early summer,
      while NH4+ concentrations were highest in winter and early spring, and PO4(3-)
      concentrations were highest in winter and summer. K+ concentrations were highest
      in spring. Na+ concentrations were highest in September and lowest in August.
      Ca2+ concentrations in stream water were highest in June and September and ranged
      from 19.4 mg x L(-1) to 44.3 mg x L(-1) during the year. Mg2+ concentrations were
      highest in March and ranged from 2.18 mg x L(-1) to 5.25 mg x L(-1) during the
      year. Cd concentrations were highest from January to April, while Pb
      concentrations were highest in November and January. The concentration of both Cd
      and Pb was lowest in autumn. The concentration of Cd ranged from 0.019 microg x
      L(-1) to 0.3265 microg x L(-1) and the concentration of Pb ranged from 0.217
      microg x L(-1) to 3.886 microg x L(-1). Mn concentrations were highest in May and
      December, while Fe concentrations were highest in spring and Zn concentrations
      were highest in March and August. According to environmental quality standards
      for surface water, stream water quality in the Huoditang forest region met the
      requirements for water quality standard I. Water quality was best in autumn and
      poorest in winter and spring.

PMID- 18613499
TI  - [Seasonality and contribution to acid rain of the carbon abundance in rainwater].
AB  - This paper reports the results from a study of the carbon abundance in rainwater
      of Guangzhou city, China. The determination of TOC, DOC, POC and PEC helps to
      study the seasonality of carbon abundance and its contribution to the acid rain.
      The results display the fact that the average contents of TOC, DOC, POC and PEC
      are 7.10 mg/L, 3.58 mg/L, 3.60 mg/L and 0.72 mg/L, respectively. These results
      confirm the deep effect of the organic pollutant to the rain. The seasonality
      exists in the carbon abundance of rainwater. The contents of TOC and DOC are up
      to the maximum in spring and the minimum in summer; the contribution of POC to
      TOC in summer is obviously higher than that in other seasons; and the relative
      content of POC is clearly higher in dry season than that in wet season. The
      seasonality reflects the more emission of the total pollutant in spring and the
      solid particle pollutant in summer than those in other seasons. Moreover, the
      emission of the organic pollutant from the mobile vehicles is more obvious in dry
      season than that in wet season. The contents of TOC and DOC have the negative
      correlation to the pH values, which confirms the contribution effect of the
      organic pollutant, such as vehicle emission, to the acid rain.

PMID- 18613500
TI  - [Impacts of different pretreatments on characteristics of excess sludge].
AB  - The impacts of three pretreatments (acid, alkaline and thermal treatments) on the
      characteristics of sludge were discussed. The results showed that the three
      pretreatments could disintegrate the sludge and the effectiveness of alkaline
      treatment was the maximum (about 58.46%) and its SCOD release was also the
      maximum (2934.9 mg/L). The main compositions of soluble organics were proteins,
      carbohydrates and volatile fatty acids (about 80%-90%, together). The increase of
      soluble proteins in the alkaline treated sludge was the maximum (2058.6 mg/L),
      while the increase of soluble carbohydrates in the thermal treated sludge was the
      maximal (353.2 mg/L). The SS and VSS of sludge were decreased by the treatments
      and the effectiveness of alkaline treatment was the best and that of acid
      treatment was the worst. The particle size distribution of sludge showed acid and
      alkaline treatments could decrease the particle size and increase the consistency
      of sludge. The solublized mechanism of the three pretreatments was also
      discussed.

PMID- 18613501
TI  - [Nitrifiers accumulation with reject water and bio-augmentation for nitrification
      of sewage at short SRT].
AB  - Sequencing batch reactor, treating simulated municipal wastewater for N removal
      and operated at near the minimum SRT (solids retention time) for nitrification
      (in reactor 2), was seeded daily with nitrifying biomass accumulated with reject
      water (in reactor 1) came from Xi' an Dengjiacun wastewater treatment plant.
      Comparison of the nitrification ability, the characteristics of the activated
      sludge before seeding and after seeding was made. The experiment result shows
      that, the maximum nitrification rate of the activated sludge in the reactor 1
      reached 81.4 mg/(L x h). The effluent concentration of NH4+ -N of the reactor 2
      decreased at a rate of 0.992 mg/(L x d) (R2 = 0.903), and the maximum
      nitrification rate increased 1.36 times. Once seeding was terminated, the
      effluent concentration of NH4+ -N increased at a rate of 1.956 mg/(L x d) (R2 =
      0.999), and nitrification caused by seeding was not completely disappeared after
      seeding was stopped for 34 d. The amount and varieties of protozoa and the value
      of SVI in the reactor seeded with nitrifiers increased during the initial time of
      seeding, but were recovered when the reactor 2 reached stable state.

PMID- 18613502
TI  - [Control of microbial communities achieved by pH adjustment and its influences on
      batch treatment of antibiotic wastewater].
AB  - Scanning electron microscope (SEM), Fluorescent in-situ hybridization (FISH)-Flow
      Cytometry (FCM) as well as Biolog method were used to discuss the effect of pH
      control during the batch treatment on the composition and catabolic diversity of
      the microbial communities obtained from antibiotic wastewater. The following
      results were obtained: 1) At the end of batch treatment, the percentages of yeast
      cells in three cultures amount to 88.20%, 54.43% and 1.75%, respectively, when pH
      levels are individually maintained at 4-5, 5-6 and 6.5-7.5 throughout three batch
      experiments. Correspondingly, the percentages of bacterial cells in three
      cultures increase with the increase of pH levels. 2) No significant differences
      are found among the catabolic diversity of three cultures while the yeast
      predominant culture has slightly less catabolic activities in Biolog FF
      microplate. 3) When bacteria gradually develop to be the dominant species in the
      culture, gradually enhanced COD removals of 34.8%, 44.8% and 61.2%, respectively,
      are achieved.

PMID- 18613503
TI  - [Contamination removal in landfill leachate by biological effect in sand layer of
      vadose zone].
AB  - Through the test of two sand columns for comparing, the effect on removal of
      pollutants in landfill leachate by biological effect in sand layer of vadose zone
      was studied. First, HgCl2 was confirmed as inhibitor of biological effect, and
      its most suitable concentration was 10 mg/L. Then, sand column 1 was leached by
      landfill leachate, and sand column 2 was leached by landfill leachate added 10
      mg/L HgCl2. The results indicated: with the time prolonged, the biological effect
      was more and more obvious. When the test was finished, the concentrations of COD
      and BOD, respectively reduced by 2724 mg/L and 2332.5 mg/L, and the concentration
      of NH4+ ascended from 1282.82 mg/L to 1745.48 mg/L, but the effect of TN removal
      was not obvious. Because the biological effect was inhibited by inhibitor of
      HgCl2 , the concentrations of pollutants kept calm when landfill leachate
      penetrated the sand column. Based on the results of experiment, the first-order
      attenuation kinetics model of biodegradation in sand column was founded.

PMID- 18613504
TI  - [Study on adsorption of bisphenol A from aqueous solution on modified activated
      Carbons].
AB  - A commercial activated carbon (WV A1100) was modified with nitric acid, sodium
      hydroxide and thermal treatment in an atmosphere of N2. Several techniques were
      used to characterize the physicochemical properties of these materials including
      BET, XPS, pH(PZC) and Boehm titration. The results indicated that the specific
      surface area of the W20 remarkably decreased after oxidized by nitric acid. But
      the amount of surface acidic oxygen-containing functional groups of the oxidized
      sample increased compared to the W20 and resulting in the points of zero charge
      (pH(PZC)) changed from 4.95 to 1.50. The changes of surface chemical properties
      of thermal treatment and sodium hydroxide treatment were opposite to the oxidized
      sample, as a result, the pH(PZC) of them was changed to near pH 7.0. However, a
      43.81% surface area of W20 was also diminished by thermal treatment. Furthermore,
      the results of BPA adsorption indicated that the oligomerization of BPA on the
      surface of activated carbon could not be formed through oxidative coupling
      reactions in the presence of dissolved oxygen. And the data of BPA adsorption on
      original sample, thermal and sodium hydroxide treatment sample were fitted to the
      Langmuir isotherm model well. Whereas the Freundlich isotherm model described the
      adsorptive behavior of the oxidized sample better. In addition, the adsorption
      capacity of thermal treatment sample was the highest and its saturated adsorption
      capacity reached 526.32 mg/g. The value was three times higher than that of the
      oxidized sample. Combined with the results of characterization, it was found that
      the hydrophobic nature and zero of net charge density of carbon surface were the
      main factors to affect the BPA adsorption on activated carbons and the adsorption
      is based on pi-pi theory.

PMID- 18613505
TI  - [Efficiency and mechanics of surfactant modified zeolite with nitrate adsorbed to
      control nitrogen and phosphorus release from sediments].
AB  - Efficiency and mechanics of surfactant modified zeolite (SMZ) with nitrate
      adsorbed to control nitrogen and phosphorus release from sediments were
      researched. The results show that: 1) The optimal level of HDTMA adsorbed on SMZ
      for nitrate sorption was 276% ECEC. The sorption of nitrate on SMZ can be well
      described by the Langmuir sorption isotherm, and the sorption capacity was 1724
      mg/kg. The nitrate sorption on SMZ was quick and the nitrate adsorbed on SMZ can
      be released. The sorption of ammonia and phosphorus on SMZ with nitrate adsorbed
      can also be well described by the Langmuir sorption isotherm, and the sorption
      capacity of ammonia and phosphorus are 12.0 mg/g and 0.597 mg/g respectively. 2)
      The barrier of SMZ with nitrate adsorbed can provide nitrate for surface
      sediments for a long time, and the quantity of released nitrate in overlying
      water was much less than that of nitrate directly added. This barrier can not
      only efficiently control ammonia release from sediments, but also control
      phosphorus release from sediment efficiently.

PMID- 18613506
TI  - [Effects of irradiance on blooms of the dinoflagellate Prorocentrum donghaiense
      Lu in the coastal area in East China Sea].
AB  - With field culture experiments and model calculations, the natural-light
      dependent growth and the optimal light layers in sea water for growth of red tide
      dinoflagellate Prorocentrum donghaiense Lu were studied in order to analyze the
      role of light on algal blooms in the coastal area in East China Sea in spring.
      The results show that the relationship of growth and light can be well described
      by Steele's equation, and the optimal light intensity (Iopt) of P. donghaiense is
      (38.2 +/- 3.8) W x m(-2), which is lower than Iopt for several other red tide
      algae (40-133 W x m(-2)), meaning that P. donghaiense may have an advantage when
      developing blooms in turbid environments where solar irradiance is easily
      attenuated. The optimal light layers for P. donghaiense growth are thicker
      offshore than inshore, and the thickness of optimal light layers in the
      subsurface water usually in 3-15 m in depth is about 5-10 m in the red tide area.
      The trade-off of light and nutrient fitness results in blooms in the so-called
      red tide area, and the light-optimum characteristic of the subsurface water is an
      important factor for the subsurface bloom development in spring.

PMID- 18613507
TI  - [Growth inhibition of Microcystis aeruginosa in packed-bed discharge plasma
      Reactor].
AB  - The paper discussed the effect of the gas flow rate and the addition of glass
      pellets dielectric on the growth inhibition of Microcystis aeruginosa (M.
      aeruginosa) and the concentration of hydrogen peroxide, the effect of energy
      input and pH on the growth inhibition of M. aeruginosa and the effect of packed
      bed reactor on the algal Chl-a and cell density. The results show that the
      increasing of the gas flow rate and the addition of glass pellets dielectric
      enhance the effect of the discharge plasma reactor on the growth inhibition of M.
      aeruginosa immediately after discharge, but the effect is unobvious. The algal
      optical density slightly increases and then markedly decreases during the
      incubation period, e.g., the removal efficiency of the algal optical density is
      high to 87.3% at the end of the fifth day at an air flow rate of 0.75 m3/h after
      40 min treatment in the packed-bed discharge plasma reactor. The concentration of
      hydrogen peroxide is enhanced by the increase in the gas flow rate and the
      addition of glass pellets dielectric into the discharge plasma reactor, too,
      especially the concentration of hydrogen peroxide enhanced from 4.6 micromol/L to
      38.3 micromol/L by the addition of glass pellets dielectric, which will enhance
      the destructive effect of hydrogen peroxide on the algae during the incubation
      period. The effect of the growth inhibition of M. aeruginosa is obvious with the
      increasing in the energy input into the packed-bed discharge plasma reactor. The
      effect of the alkaline solution on the growth inhibition of M. aeruginosa is more
      higher than that of the acidic solution, and the value of pH is increased under
      the acidic condition and decreased under the alkaline condition, but the tread of
      pH is to be neutral during the incubation period. The decrease of the content of
      Chl-a and cell density is marked in this reactor, and at the end of the fifth
      day, the removal efficiencies of Chl-a and cell density are high to 100%.

PMID- 18613508
TI  - [Research of a bioluminent bacterial-based optical fiber sensor to detecting
      acute effects of pollutants in water].
AB  - Field detection of general toxicity is urgent demand in these years, therefore
      rapid, sensitive, convenient biosensor was studied to detect cute toxicity of
      water pollutant, which is a novel optical fiber sensor immobilized bioluminent
      bacterial, Photobacterium phosphorem T3. This bioluminence light was measured by
      light detection system after it coupling to optical fiber. For the activity and
      bioluminence of bacterial was seriously affected by immobilizing conditions,
      optimization of immobilization was studied, including the concentration of Sodium
      alga gel and CaCl2, immobilizing time, pH, and the preservation time. When the
      bacteria was immobilized with 3% sodium alga in 3% CaCl2 solution for 15 minutes,
      the bacteria had the best activity, and the immobilized bacteria would maintain
      its activity for the longest time in the 3% NaCl solution. The dose-response
      curves of Zn2+, NH3, nitrobenzenne and cresol are detected, and the EC50 are also
      calculated, which are 5.1, 10.2, 70.4, 77.0 mg x L(-1). The EC50 are quite
      coherent to the results of standard bioluminescent bacteria method. The optical
      fiber biosensor could be disposable, small sized, convenient operation for field
      application.

PMID- 18613509
TI  - [Construction of external standard for detection of rotavirus in water using the
      quantitative real-time polymerase chain reaction].
AB  - To construct external standard for detection of rotavirus in water using the
      quantitative real-time polymerase chain reaction, rotavirus cDNA standard for
      real-time PCR assay was prepared by cell culture, PCR and T-A clone methods with
      primers specific for the viral structure protein VP7 gene, and this cDNA standard
      was confirmed by enzyme cleavage and DNA sequencing. Specificity, stability and
      reproducibility of the cDNA standard quantified were detected by common
      polymerase chain reaction (PCR) and quantitative real-time PCR. The results of
      standard curve showed a very good linear negative regression between threshold
      cycle (Ct) and Log starting quantity of copy number. The melting curve analysis
      of real-time PCR showed melting temperature at 81 degrees C +/- 0.5 degrees C,
      indicating PCR products were that of the rotavirus VP7 sequence and thus the
      standard used in this study was specific for rotavirus. Moreover, the result of
      real-time PCR also indicated detection range was from 9 x 10(0) to 9 x 10(11)
      copies per reaction, and the detection limit for this assay was 9 copies of
      rotavirus cDNA per reaction, and thus real-time PCR assay using the standard had
      a high sensitivity for detection of rotavirus. Furthermore, the results indicated
      a high stability and reproducibility of cDNA standard were assessed according to
      the CVs of three independent experiments in the range of 0.2%-0.9%. Taken
      together, in this study rotavirus cDNA standard prepared could be used as
      quantitative detection of rotavirus cDNA from water samples.

PMID- 18613510
TI  - [Induced apoptosis and mechanism of endosulfan in mouse germ cells].
AB  - Endosulfan which is going to be included as POPs in effect of organism have
      become the focus of international concern. To explore endosulfan on apoptosis of
      spermatogenic cells and mechanisms, doses of 7.0, 3.5 and 1.75 mg/kg oral
      administration to mice exposed to 28 consecutive days. Morphology characters of
      spermatogenic cells observed by laser confocal scanning microscope (LCSM), DNA
      ladder detected by electricity swims, and increasing of DNA degeneration rate
      measured through diphenylamine (p < 0.01). Endosulfan might enhance calcium
      concentration in the spermatogenic cells and restrained Na+ K+ -ATPase and Ca2+
      Mg2+ -ATPase activities that showed endosulfan might induce spermatogenic cells
      in the testicle to occur apoptosis (p < 0.01), to cause the function of
      transporting Ca2+ to be limited, reduce the ability of excluding calcium and send
      Ca2+ concentration to hoist sustainingly,i.e. calcium overload in the cells.

PMID- 18613511
TI  - [Impact of benzo [a] pyrene the expression of mitochondrion-encoded genes in the
      earthworm Eisenia fetida].
AB  - The earthworm Eisenia fetida's benzo [a] pyrene (BaP) exposure experiments were
      carried out in artificial soil according to ISO 11268-1:1993. And then the
      upregulated and downregulated subtractive cDNA libraries were constructed by
      Clontech PCR-Select cDNA Subtration Kit. From the BaP exposure upregulated
      subtractive cDNA library, several cDNA segments matched mitochondrion-encoded
      genes were found, including cytochrome c oxidase subunit I (CO I), subunit II (CO
      II), subunit Ill (CO III), NADH dehydrogenase subunit 1 (NDH1), and ATP synthase
      subunit 6. The result indicated BaP and the subsequent oxidative stress disturbed
      the expression of mitochondrion-encoded genes, and this was potential biomarker
      for oxidative stress following xenobiotic exposure.

PMID- 18613512
TI  - [QSPR studies on the physicochemical properties of polybrominated diphenyl ethers
      using theoretical descriptors derived from electrostatic potentials on molecular
      Surface].
AB  - Geometrical optimization and electrostatic potential calculations were performed
      at the HF/6-31G* level for all 209 polybrominated diphenyl ethers (PBDEs), which
      are a group of persistent organic pollutants. Linear relationships between gas
      chromatographic relative retention time (RRT), n-octanol/air partition
      coefficient (lgK(0A)) and 298 K supercooled liquid vapour pressures (lg P(L)) of
      PBDEs and theoretical descriptors of molecular structure were established by
      multiple regression method. The result shows that the parameters derived from
      electrostatic potential, together with the number of the bromine atoms on the two
      phenyl rings, can be preferably used to express the quantitative structure
      property relationships of PBDEs. The leave-one-out cross-validate coefficients
      (Rcv) are 0.9819, 0.9911 and 0.9963, and standard deviations (SD) are 0.0424,
      0.1384 and 0.1020, respectively, for these three models. This reveals that all
      these models have high predictive capabilities. The molecular electrostatic
      potentials are proved to have the general applicability in QSPR model of PBDE
      congeners.

PMID- 18613513
TI  - [Accumulation characteristics of PAHs in multimedia from various urban functional
      areas].
AB  - Taking Shanghai city as an example, the study analyzed the difference of
      concentration levels in road dust, soil and leaves besides roads. The reasons and
      mechanisms of the accumulation characteristics were also been discussed. The
      result shows that, in a same functional area, road dusts and soils accumulated
      more PAHs while leaves did less, and the concentrations of PAHs in P. orientalis
      L. leaves were higher than those in Buxus sinica leaves. Total PAHs
      concentrations in road dust and soil ranged from 8992 ng x g(-1) to 141723 ng x
      g(-1), averaged in 54964 ng x g(-1), and from 9306 ng x g(-1) to 146689 ng x g(
      1), averaged in 56883 ng x g(-1), respectively. Total PAHs concentrations in P.
      orientalis L. leaves and Buxus sinica leaves varied from 2423 ng x g(-1) to 32883
      ng x g(-1), with a mean value of 12983 ng x g(-1), from 1498 ng x g(-1) to 19418
      ng x g(-1), with a mean value of 7612 ng x g(-1). Among various functional areas,
      there were significant differences in PAHs concentrations in road dusts and soils
      while those in leaves were similarly. PAH homologue concentrations in road dusts
      and soils had significant difference in various functional areas with the
      priority of high molecular homologues. However, PAH homologue concentrations in
      leaves were similarly dominated by low molecular homologues. The accumulation
      characteristics were closely corresponding with the physicochemical property of
      PAHs and the main accumulation ways of PAHs in multimedia.

PMID- 18613514
TI  - [Concentrations and distribution of heavy metals in urban sewage discharge
      channel of Tianjin].
AB  - Concentrations of metals, organic matter(OM), total nitrogen (TN) and total
      phosphorus (TP) were determined in sediment and soil samples collected from 15
      selected sites along Dagu sewage discharge channel in Tianjin, China. Relative
      enrichment factors and correlation analysis were taken to study the distribution
      and pollution level of metals. The results show that pollution level is more
      serious in sediment than that in soil. Hg, Cd, Zn and Pb are more enriched while
      Cr, Ni and As are less enriched. Relative enrichment factors (REF) of Hg, Cd, Zn
      and Pb in sediment are 59.3, 25.4, 14.5 and 7.5, and that in soil are 8.44, 5.19,
      6.6 and 3.3, respectively. The heavy metal concentrations greatly vary among
      different sampling sites, which is demonstrated by the fact that coefficient of
      variation (CV) varies from 74.4% to 110.8% in sediment. The highest enrichments
      of heavy metals are found in sampling site S4 and S12, which are affected by
      chemical industry wastewater. There is no significant correlation between metal
      concentrations in sediment and those in soil. The concentrations of heavy metals
      in sediment are not reciprocally correlated, either. However, significant
      correlations exist among many pollutants in soil. Hg, Cd, Zn and Pb are
      positively correlated with each other, at the same time they are positively
      correlated with OM, TN and TP, but Cr, Ni and As are poorly correlated with OM
      and TP, which suggests that Cd, Zn and Pb have similar environmental geochemical
      properties and are contaminated by anthropogenic impact. When compared with the
      main rivers in Tianjin, the enrichment of heavy metals in Dagu sewage discharge
      channel is relatively high.

PMID- 18613515
TI  - [Comparison of characteristics of heavy metals in different grain sizes of
      intertidalite sediment by using grid sampling method].
AB  - 384 surface sediment samples were collected from mud flat, silt flat and mud-silt
      flat of Bohai Bay by 1 m and 10 m interval using grid sampling method.
      Concentrations of Al, Fe, Ti, Mn, Ba, Sr, Zn, Cr, Ni and Cu in each sample were
      measured by ICP-AES. To figure out the random distribution and concentration
      characteristics of these heavy metals, concentration of them were compared
      between districts with different grain size. The results show that varieties of
      grain size cause the remarkable difference in the concentration of heavy metals.
      Total concentration of heavy metals are 147.37 g x kg(-1), 98.68 g x kg(-1) and
      94.27 g x kg(-1) in mud flat, mud-silt flat and silt flat respectively. Majority
      of heavy metals inclines to concentrate in fine grained mud, while Ba and Sr have
      a tendency to concentrate in coast grained silt which contains more K2O * Al2O3 *
      6SiO2. Concentration of Sr is affected significantly by the grain size, while
      concentration of Cr and Ti are affected a little by the grain size.

PMID- 18613516
TI  - [Evaluation on environmental quality of heavy metals in agricultural soils of
      Shanghai].
AB  - Contents of heavy metals (Cu, Zn, Pb, Cd, Cr, Hg and As) in agricultural surface
      soils from Shanghai were analyzed. Different evaluation methods and assessment
      standards of heavy metals were also used for comparison. In addition, inverse
      distance interpolation (IDW) method was also applied to study the spatial
      variability of heavy metals pollution, based on GIS. The results show that mean
      concentrations of heavy metals in soils all exceeded their corresponding natural
      background values, except for As. Compared mean concentrations of heavy metals
      with the National Standard, the soils were not contaminated. All the determined
      heavy metals excluding Pb in some regions, however, exceeded the critical values
      of national soil quality standard. Additionally, it is indicated that most of
      cropland soils were good, and the ratio of good soil, certified soil and
      disqualified soil were 71.4%, 94.9% and 5.1%, respectively. Most of the
      disqualified soils, which distributed in Jiading and Pudong, however, have been
      urbanized and covered with buildings and factories. Moreover, the soil quality
      was influenced by different heavy metals at different levels, thus the regional
      differentiation of soil pollution was obvious. Zn, Cd and Hg were the dominant
      elements causing soil heavy metal pollution in the study area. Furthermore, it
      was found there was a close relationship between the urban distribution and heavy
      metal pollution of the soils. Therefore, it is concluded that with the expanding
      of urbanization, a new polluted area may appear.

PMID- 18613517
TI  - [Dynamic characteristics of phosphorus in purple paddy soil and its environmental
      Impact].
AB  - The dynamic characteristics of phosphorus (P) in the surface water and runoff of
      paddy field with different P fertilizing treatments were investigated using the
      field experiment under the independent irrigation system as well as its
      environmental impact. The results showed that the concentration of total
      phosphorus (TP) in the surface water increased as the fertilizing amounts
      enhanced and reached the peak values after 24 h for all treatments in range of
      0.928-3.824 mg/L. And the fluctuation of TP concentration in surface water was
      drastic during the first 30 days with the average contents of 0.259-1.433 mg/L
      which exceeded the critic values of eutrophication. Therefore, the field
      managements such as inter-tillage and drainage should be avoided during the time.
      After 40 days, the TP concentration declined slowly and then came to
      stabilization with low values after 60 days. The contents of different P forms in
      the runoff water increased with the improved amounts of precipitation and
      fertilizing and above 50% was dissolved phosphorus (DP). The DP was the dominant
      one in the P loss of the purple paddy soil and the loss load changed between
      0.358 and 2.579 kg/hm2. Additionally, the P loss more easily occurred for the
      treatment of utilizing the cattle manure than that of straw, approximately 40% of
      loss load higher. Both the loss load and apparent P loss ratio evidently declined
      with the treatment of fertilizer combined with straw, suggesting that it was the
      better measure for reducing the P loss in the paddy field.

PMID- 18613518
TI  - [Effects of acidification and liming on organic matter leaching in forest soil].
AB  - The potential effects of acidification and liming on the dynamics of carbon pool
      in forest soil were studied through field experiments at Tieshanping, Chongqing
      in Southwest China. The changes of dissolved organic matter (DOM) concentration
      in soil water in different layers within three years after application of
      limestone or magnesite indicated that soil remediation had leaded to significant
      decrease of DOM in soil water from mineral layers [e.g., DOC concentration in the
      upper layer decreased from (20.32 +/- 3.19) mg x L(-1) in the reference plots to
      (15.69 +/- 2.39) mg x L(-1) in limestone plots and (11.44 +/- 1.87) mg x L(-1) in
      magnesite ones] as probably the results of increasing pH value and decreasing ion
      strength, although the DOM leaching from the litter layer was found increasing,
      especially in the first half year. Consequently, liming may not in longterm
      accelerate the transport of soil organic mater downward from the litter layer to
      the mineral layer, but prevent the acidified soil from DOM-leaching and thus
      carbon-pool losing.

PMID- 18613519
TI  - [Estimating photosynthesized carbon distribution and inputs into belowground in a
      maize soil following 13C pulse-labeling].
AB  - Evaluating the contribution of maize growth to soil organic carbon is important
      for the understanding of the relationship of farmland carbon balance and
      agriculture production. 4 times of 13C pulse-labelling were used to estimate the
      photosynthesized carbon distribution at different development stages (seedling,
      elongation, heading and grain-filling) in maize-soil system, and quantify the
      carbon inputs into each part of belowground in whole growth season. The result
      indicated that the 13C retained aboveground reached its maximum: 80.01% among net
      assimilated 13C at grain-filling stage labelling. For the 4 labelling stages, the
      13C transferred into belowground is 43.24%, 46.46%, 30.30% and 19.99%
      respectively, and of the 13C input into belowground, 34.68%-77.56% was respired
      by rhizosphere, 16.63%-57.02% was remain in roots and 5.05%-8.30% was
      incorporated into soil organic carbon by rhizodeposition. During the whole growth
      season of maize, the photosynthesized carbon allocated to aboveground, roots,
      rhizosphere respiration and soil organic carbon was 62.39%, 17.88%, 17.07% and
      2.67% of the net assimilated carbon. At elongation, heading and grain-filling
      stages, maize's rhizosphere respiration accounted for 67.07%, 63.31% and 28.82%
      of the total CO2 efflux from the soil respectively, during the same period
      rhizosphere priming effect led to 31.11%, 79.09% and 120.83% increase of
      decomposition of original soil organic carbon respectively. Based on the
      calculation of 18 t x hm(-2) dry matter of maize for farmland production and its
      C content is 42%, the total carbon transferred into belowground is 4.6 t x hm(
      2), among which 2.1 t x hm(-2) was respired by rhizoshphere, 2.2 t x hm(-2) was
      retained in roots and 0.33 t x hm(-2) was incorporated into soil organic carbon.

PMID- 18613520
TI  - [Field scale demonstration of fungi-bacteria augmented remediation of petroleum
      contaminated soil].
AB  - Pilot demonstration of the fungal-bacterial augmented in situ remediation of
      petroleum contaminated soil was carried out in Zhongyuan Oilfield, Henan, using
      artificially prepared soil, newly and aged contaminated soil as sample,
      respectively. For the first run of the experiment started from Nov. 5, 2004 and
      lasted for 122 days, the removal of contaminate was 61.0%, 48.3% and 38.3% for
      diesel, lube and crude oil, respectively. For the second run started from May 18,
      2005 and lasted for 161 days, the removal of TPH was 75% for the artificially
      contaminated soil sample while 46.0% and 56.6% for the fresh and aged
      contaminated soil. The removal of high concentration salt was involved in the
      remediation of the freshly and aged contaminated soil. The changes of the
      petroleum composition was monitored during the remediation process, which
      confirmed the effective degradation of alkanes, aromatic hydrocarbons and non
      hydrocarbon compounds by the fungi-bacteria consortia, as compared to that
      obtained without the inoculation of the consortia. To further demonstrate the
      remediation, wheat was planted in above reclaimed soil. While wheat production in
      the reclaimed artificially contaminated soil yielded nearly as much as that
      obtained in the normal farmland, the output of wheat in the reclaimed refresh and
      aged contaminated soil was 57.2% and 70.3% of the averaged output of the normal
      farmland. The above results further confirmed the workability of fungal-bacterial
      augmented in situ remediation of petroleum contaminated soil and its application
      potential as well.

PMID- 18613521
TI  - [Isolation of functional bacteria guided by PCR-DGGE technology from high
      temperature petroleum reservoirs].
AB  - It is a brand-new method to isolate functional bacteria from high temperature
      petroleum reservoirs according to the sequence information obtained from PCR-DGGE
      patterns. Three-set primers of 16S rDNA high variable region, V3, V8, V9, were
      compared. The results showed that more microbial diversity information could be
      obtained from the PCR product of V9 region. Sequence analysis indicated that the
      dominant bacteria in the petroleum reservoir had high sequence similarity with
      bacteria from alpha, beta, gamma-Proteobacterias and Bacilli from the GenBank
      database. According to the sequences information, multi-cultivation technology
      including enrichment cultivation, special cultivation and direct cultivation
      methods were employed, and finally, five strains (three strains by traditional
      methods) were isolated from oil-water samples. Among them, three thermophilic
      hydrocarbon-degrading bacteria, which belonged to Bacillus sp., Geobacillus sp.
      and Petrobacter sp., respectively, could grow well under 55 degrees C in obligate
      anaerobic condition. The crude oil could be utilized by these strains with the
      degradation rate of 56.5%, 70.01% and 31.78% respectively along with the
      viscosity reduction rate of 40%, 54.55% and 29.09%, meanwhile the solidify points
      of crude oil were reduced by 3.7, 5.2 and 3.1 degrees C. Therefore, the
      combination of sequence information from PCR-DGGE and altering cultivation
      conditions is an available novel method to isolate more functional microorganisms
      which could be utilized for microbial enhanced oil recovery.

PMID- 18613522
TI  - [Determination of 16S rRNA gene sequence for a new ANAMMOX bacterial species].
AB  - The anaerobic ammonium oxidation (ANAMMOX) activity of the sludge was about 9.84
      x 10(-4) mg x (mg x h)(-1) by measuring the simultaneous consumption of ammonium
      and nitrite under anoxic conditions in the batch tests. The consumption of NO2(-)
      -N and NH4+ -N was 1.311 for ANAMMOX bacteria. The partial 16S rDNA sequence was
      obtained by using molecule biology methods. Crude DNA of the total bacteria in
      granular sludge from EGSB reactor was extracted and purified. Then, PCR
      amplification by using specific primer, clone and sequence determination was
      performed. ANAMMOX bacterial species(anaerobic ammonium-oxidizing Planctomycete
      cquenviron-1) which was enrichment cultivated from EGSB reactor were the same
      genera with Candidatus "Anammoxoglobus propionicus" and Candidatus "Jettenia
      asiatica" by analyzing phylogenetic tree. The maximum identities of anaerobic
      ammonium-oxidizing Planctomycete cquenviron-1 with other ANAMMOX bacterial
      species was about 93%. The results showed that a new ANAMMOX bacterial species
      which was enrichment cultivated from EGSB reactor was found and anaerobic
      ammonium-oxidizing Planctomycete cquenviron-1 was denominated.

PMID- 18613523
TI  - [Influence of community structure of phosphorus removing bacteria under oxygen
      contain in processes for phosphorus removal].
AB  - It was studied for community structure of microorganisms in the phosphorus
      removal processes under the circulating situation, and analyzed for
      microorganism's structure and behavior characteristics by the molecular biology
      technique with direct obtaining of DNA from samples of activated sludge, and by
      nested PCR and DGGE. It was also determined community structure of
      microorganisms. It was analyzed structures of Proteobacteria and Acidobacterium
      by 16S rDNA V3 area gene fragments sequences in activated sludge. By comparing
      gene sequences in the National Center of Biological Information (NCBI), were
      determined the kinds of part of microorganisms. Analyzing the low of changes of
      preponderant bacteria in anaerobic/aerobic and anaerobic/anoxic conditions takes
      to know, that under the stable situation of phosphorus removing, the system of
      microorganism's structure can kept mostly constant. Minority races that have
      changed in amount or kind has something to do with the variation of oxygen level
      in the system, but structure totally can adapt the environmental conditions of
      the processes, while it placed in dynamic varieties.

PMID- 18613524
TI  - [Isolation and identification of phenol-degrading strains and the application in
      biotreatment of phenol-containing wastewater].
AB  - Ten phenol-degrading bacterial strains were isolated from mixture of activated
      sludge and wastewater of a petroleum chemical plant. The five isolates (PD1, PD2,
      PD6, PD7 and PD39) were identified as Pseudomonas sp.,the four (PD4, PD5, PD8 and
      PD9) as Acinetobacter sp.,and the one (PD3) as Comamonas sp.by 16S rDNA sequence.
      Biodegradation characteristics of phenol, optimal conditions for growth,
      substrate range, activities of catechol 1,2-dioxygenase and catechol 2,3
      dioxygenase, and biotreatment of phenol-containing wastewater of Pseudomonas
      sp.PD39 were investigated in detail. The results indicated that the optimal
      conditions for growth and degradation of strain PD39 are beginning pH of medium
      7.0, growth temperature 30 degrees C, concentration of phenol 800 mg/L. PD39 was
      capable of metabolizing phenol at concentrations up to 1200 mg/L and removing 637
      mg/L in industrial wastewater by 99.96% in 72 h. This strain possesses a good
      application potential as a bioaugmentation strain in the activated sludge system
      for treatment of phenol-containing wastewater.

PMID- 18613525
TI  - [Isolation, identification and degradation characteristics of a quinoline
      degrading bacterium Rhodococcus sp QL2].
AB  - A quinoline-degrading bacterium QL2, which utilizes quinoline as sole source of
      carbon, nitrogen and energy, was isolated from activated sludge in a coke-plant
      wastewater biological treatment system. According to the morphological
      characteristics, physiological and biochemical characteristics, and sequence
      analysis of 16S rRNA, the strain was identified as Rhodococcus sp.. The optimal
      temperature, initial pH, and shaker rotary speed for strain QL2 utilizing
      quinoline are 35-42 degrees C, pH 8-9, and 150 r/min, respectively. Extra
      nitrogen sources stimulate the isolate growth on quinoline, and inorganic
      nitrogen better than organic nitrogen, NH4+ -N better than NO3(-) -N. The
      degradation reaction of quinoline by strain QL2 can be described with zero order
      kinetic equation within the initial quinoline concentrations of 60-680 mg/L. When
      the initial concentration was 150 mg/L, quinoline was degraded completely in 8
      hours and TOC removal efficiency was 70% in 14 hours. This bacterium produced
      pigmented compounds, and ring nitrogen was released into the growth medium as
      ammonium. The main intermediate in the degradation pathway was 2-hydroxyquinoline
      by the analysis of HPLC and GC/MS. With a broad range of substrate utilization,
      the strain can degrade phenol, naphthalene, pyridine, and some other kinds of
      aromatic compounds.

PMID- 18613526
TI  - [Kinetics model for batch culture of white rot fungus].
AB  - In order to understand ligninolytic enzymes production process during culture of
      white rot fungus, accordingly to direct the design of fermentation process, a
      kinetics model was built for the batch culture of Phanerochaete chrysosporium.
      The parameters in the model were calibrated based on the experimental data from
      free and immobilized culture separately. The difference between each variable's
      values calculated based on kinetics model and experimental data is within 15%.
      Comparing parameters for the free and the immobilized culture, it is found that
      maximum biomass concentrations are both 1.78 g/L; growth rate ratio of
      immobilized culture (0.6683 d(-1)) is larger than that of free culture (0.5144 d(
      1)); very little glucose is consumed for biomass growth in free culture while in
      immobilized culture much glucose is used and ammonium nitrogen is consumed at a
      greater rate. Ligninolytic enzymes production process is non-growth related;
      fungal pellets can produce MnP (231 U/L) in free culture with a production rate
      of 115.8 U x (g x d)(-1) before peak and 26.1 U x (g x d)(-1) after peak, thus
      fed-batch is a possible mode to improve MnP production and fermentation
      efficiency. MnP (410 U/L) and LiP (721 U/L) can be produced in immobilized
      culture, but MnP and LiP production rate decrease from 80.1 U x (g x d)(-1) and
      248.9 U x (g x d)(-1) to 6.04 U x (g x d)(-1) and 0 U x (g x d)(-1),
      respectively, indicating a proper feed moment is before the enzymes peak during
      fed-batch culture.

PMID- 18613527
TI  - [White rot fungi biofilter treating waste gas containing chlorobenzene].
AB  - A novel gas-solid phase bioreactor, using bamboo as support material, inoculated
      with white rot fungi Phanerochaete chrysosporium was established to treat waste
      gas containing chlorobenzene. The performance of P. chrysosporium bioreactor was
      examined under different conditions. Results showed that the maximum removal
      efficiency of nearly 80% (average removal efficiency of 50%) could be reached
      under the condition of chlorobenzene inlet concentration of 200-1500 mg/m3 and
      the empty bed retention time (EBRT) of 122 s. While the maximum chlorobenzene
      removal rate of 94 g/(m3 x h) [average removal efficiency o f 60 g/(m3 x h)] had
      been achieved within chlorobenzene inlet concentration of 500- 1500 mg/m3 and at
      the flow rate of 0.5 m3/h. Furthermore, the removal rates of the bioreactor at
      different flow rates were also examined, suggesting that the response of removal
      rate to the change of inlet loading was dependent on the flow rate. Lower flow
      rate could promote the extent of removal rate enhancement compared to the higher
      flow rate. Moreover, the profile of chlorobenzene concentration along the height
      of the biofilter showed a nonlinear decrease trend.

PMID- 18613528
TI  - [Effects of cadmium on the growth and nitrogen metabolism in Brassica chinensis].
AB  - Hydroponic culture was conducted to study the effect of Cd on the growth, metal
      accumulation and nitrogen metabolism in Brassica chinensis. The enzymatic
      activities of nitrogen metabolism including nitrate reductase (NR), glutamine
      synthetase (GS) and GS-transferase as well as the concentrations of chlorophyll,
      free proline, soluble protein, NO3(-) -N, NH4+ -N and nutrients in Brassica
      chinensis were determined. Results indicated that the addition of Cd reduced the
      content of the soluble protein and the accumulation of Cu, Ca, Fe and Mg, but
      promoted the P uptake. Low level of Cd (1 mg x L(-1)) could significantly
      increase the biomass and the content of chlorophyll of Brassica chinensis and the
      activities of NR, GS and GS-transferase when compared to control plants. However,
      when the Cd levels were above 2.5 mg x L(-1) in the culture medium, the
      activities of these enzymes were inhibited. Accordingly, the contents of NO3(-) 
      N, NH4+ -N, free proline and the activity of protease in the leaf of Brassica
      chinensis increased significantly. These results suggested that Cd addition could
      interfere with the assimilation of N in Brassica chinensis. The increase of free
      proline might alleviate the toxicity of ammonium in Brassica chinensis.

PMID- 18613529
TI  - [Electricity generation using the packing-type microbial fuel cells].
AB  - The packing-type microbial fuel cells (MFCs) were constructed using the granular
      graphite and the carbon felt as packing materials. The start-up time of the
      packing-type MFC was about 1 d, which was lower than that of the flat-type MFC.
      The maximal power density (Pm) of the MFC with carbon felt as packing material
      was 1502 mW/m2 (37.6 W/m3), which was higher than that with granular graphite as
      packing material. The carbon felt and carbon paper were sintered together to
      enhance the electric conductivity. Compared with the flat-type MFC, the area
      specific resistance of the packing-type MFC decreased from 0.071 omega x m2 to
      0.051 omega x m2, the maximal current density increased from 3000 mA to 8000 mA,
      the Pm increased from 1100 mW/m2 (27.5 W/m3) to 2426 mW/m2 (60.7 W/m3) and the
      potentials of anode decreased about 100 mV. The flow rate affected the power
      generation of the MFC. When the flow rate was lower than 1 mL/min, the Pm dropped
      with the flux decreasing. The packing-type MFC was operated for over 30 and the
      coulomb efficiency was about 10.6%.

PMID- 18613530
TI  - [Experimental investigation of nano-TiO2 on combustion and desulfurization
      Catalysis].
AB  - Experiment research of nanometer TiO2 catalytic combustion to CaO desulfurization
      was studied. Desulfurization effect was measured by the composition analysis of
      fly ash after combustion and the content of SO2 in flue gas. The effects of
      analytical grade CaO desulfurization by nanometer TiO2 addition, Ca/S molar
      ratio, nanometer TiO2 that was prepared at different conditions and combustion
      temperature were discussed. Desulfurization effects were compared with different
      coals and Ca-base agents by nanometer TiO2 addition. The reaction products
      wereanalyzed by X-ray diffraction analysis (XRD) and scanning electron microscopy
      (SEM) analysis. The combustion desulfurization mechanisms of CaO by nanometer
      TiO2 addition were discussed. The experiment results show that nanometer TiO2 has
      good catalytic effect to CaO combustion desulfurization. When nanometer TiO2 was
      added together with CaO, the optimal addition dosage of nanometer TiO2 is 8%,
      Ca/S molar ratio is 2 and the combustion temperature is 850 degrees C. The
      desulfurization efficiency of analytical and industrial grade CaO catalyzed by
      nanometer TiO2 can achieve to 87.8% and 60.3%, and it increased 13.4% and 29.6%
      than that without nanometer TiO2. The pore diameter and surface area of different
      coal ashes with nano-TiO2 addition increase because of the active centers of nano
      TiO2 surface which are helpful to the diffusion of SO2 and reaction of SO2 to SO3
      and increase the desulphurization efficiency of CaO.

PMID- 18613531
TI  - [Thermal desorption behavior of PCDD/Fs on the fly ash].
AB  - The article studied the thermal desorption behavior of PCDD/Fs on the fly ash
      under anoxic conditions. From the analysis of the PCDD/Fs concentrations in the
      gas phrase and solid residual, the several kinds of potential chemical reaction
      and physical changes of dioxin that occur at the different temperature are
      concluded. At the same time, desorption ratios of 17 toxic dioxin congers and the
      better desorption conditions are studied. At 200 degrees C and 300 degrees C, the
      average desorption ratio of PCDD/Fs are 96.2% and 95.5% respectively. At 400
      degrees C, the average desorption ratio of PCDD/Fs is 99.7%. The experiment
      results show that the PCDD/Fs is dechlorinated at 300 degrees C. At 400 degrees
      C, a lot of precursor reactions happen in the fly ash, which enhance the content
      of PCDD/Fs.

PMID- 18613532
TI  - [Acid neutralizing capacity and elements leaching behavior from MSWI fly ash
      under static pH condition].
AB  - The acid neutralizing capacity (ANC) and elements leaching behavior from fly ash
      were studied using a pHstat titration test. The pH value of the system was kept
      at 4, 5, 6 and 7 for 150 hours respectively. The concentration of major and heavy
      metals in the solution was determined. The results indicate that in the initial
      time of the titration, the amount of consumed acid increases rapidly. With the
      accumulation of the ions in the solution, the rate of the fly ash dissolution
      gets an inflection point after about 20 hours. With the fall of the controlled pH
      values, the proton buffering capacity of fly ash increases correspondingly.
      Elements represent different types of leaching behavior during the titration. The
      leaching of K, Na,Ca and Cl is not controlled by the buffing process. Si and
      SO4(2-) reached the maximal release after several hours, followed by a decrease
      in concentration. The release of Cd, Zn is similar to the acid neutralizing
      capacity and the leaching of Cu, Pb and Cr is lower than the ANC. The result of
      pH static titration can provide more detailed information about the neutralizing
      process and the potential leachability of heavy metals, and this is useful to
      evaluate the long term leaching behavior of heavy metals.

PMID- 18613533
TI  - [Traditional and microwave acid extraction of heavy metals from MSWI fly ash and
      their redistribution of fractions].
AB  - HCl was used as extractant to leach Cd, Cr, Cu, Mn, Ni, Pb and Zn from municipal
      solid waste incinerator (MSWI) fly ash under traditional and microwave acid
      extraction conditions. The redistributions of heavy metals were determined using
      the sequential extraction procedure before and after extraction. The extraction
      efficiencies and speciation transformation of heavy metals were investigated. The
      result indicated that acid extraction can extract heavy metals effectively and
      extraction efficiencies of heavy metals following the sequence of Zn
      approximately Pb > Cd > Mn > Cu > Cr > Ni. The microwave energy can improve the
      extraction efficiencies evidently. By the treatment with 1 mol/L HCl, 80.17% of
      Cd, 15.05% of Cr, 58.25% of Cu, 62.42% of Mn, 8.88% of Ni, 89.25% of Pb and
      93.03% of Zn were extracted under the condition of L/S at 25 mL/g fly ash,
      radiation time at 7 min. The results of sequential extraction procedure reveal
      that fractions of exchangeable, carbonate, Fe-Mn oxide decreased significantly
      after acid extraction and the remaining heavy metals mostly bound to residual
      form. Acid extraction process can increase the environmental safety of fly ash.

PMID- 18613534
TI  - [Effect of using three stages inoculation controlled by temperature on organic
      matter transformation during composting process].
AB  - In order to accelerate composting efficiency, municipal solid wastes (MSW)
      composting was conducted using three stages inoculation controlled by temperature
      (TSCT). At different composting phases, the samples were taken for the
      determination of organic matter transformation. Compared to routine inoculation
      method (CK), total organic carbon (TOC), dissolved organic matter (DOM) of TSCT
      decrease by 6.37%, 6.57%; and humic substance (HS), humic acid (HA), and
      humification index (HI) of TSCT increase by 8.61%, 16.75%, 18.40% at 336 hours of
      composting, respectively. Elemental analysis indicates C/H, O/C of HA molecule in
      CK increase by 8.33%, 6.25%; and those of TSCT increase by 18.33%, 11.48% at
      final stage of composting, respectively. These results all lead to the similar
      conclusion that TSCT would accelerate humification degree, and increase the
      efficiency of composting.

PMID- 18613535
TI  - Interactions between malaria workers and clinical malaria patients in Jepara
      District, Indonesia.
AB  - In a one-year longitudinal study of all clinical malaria cases treated by the
      Village Malaria Workers (VMWs) during 1999-2000, data on health-seeking behavior
      during a seven-day illness period were collected using a diary; 24 interactions
      were audiotaped. The results showed that 87% of cases had been treated by the
      VMWs on day four of the illness period. On day two, the percentage not treated
      was significantly higher in male as compared with female cases (p = 0.01) and in
      those below 15 years of age as compared with those 15 years and older (p <
      0.001). "Not doing anything" and "using VMWs only" were the two most common
      actions. Interactions between the VMWs and the patients focused on medical tasks,
      and low compliance with treatment was a common concern of the VMWs. The concept
      of preventive measures and the role of mosquitoes were lacking in the
      interactions.

PMID- 18613536
TI  - Dose ranging studies of new artemisinin-piperaquine fixed combinations compared
      to standard regimens of artemisisnin combination therapies for acute
      uncomplicated falciparum malaria.
AB  - To determine the optimum dose of artemisinin-piperaquine combination therapies
      for acute uncomplicated Plasmodium falciparum malaria, we examined 7 candidate
      regimens in 411 patients admitted to the Bangkok Hospital for Tropical Diseases.
      The studies were performed from May 2005 to October 2005 and November 2005 to
      June 2006. We compared 3-day courses of artesunate-mefloquine, artemether
      lumefantrine (Coartem) and of dihydroartemisinin-piperaquine (Artekin) as
      reference antimalarial treatments, with candidate regimens using 2-3 day courses
      of artemisinin-piperaquine, Artequick. Initially, patients receiving each of the
      regimens had a rapid clinical and parasitological response. All treatments were
      well tolerated and no serious adverse effects occurred. The 28-day cure rates
      were < 80% for the 2-day treatments with artemisinin-piperaquine at 2.4 mg/kg and
      14.4 mg/kg, respectively, in the first study period and artemisinin-piperaquine
      at 3.2 mg/kg and 16.0 mg/kg, respectively, but > 98% for the 3-day regimens.
      These results suggest that a 3-day course of artemisinin-piperaquine at 3.2 mg/kg
      and 16.0 mg/kg, respectively, deserve further evaluation as an alternative
      treatment for multidrug-resistant P. falciparum malaria.

PMID- 18613537
TI  - Interactions between antiplasmodial 3,6-diamino-1'-dimethyl-9-anilinoacridine and
      hematin and concanamycin A.
AB  - Antiplasmodial 9-anilinoacridine derivatives exert their effects either by
      inhibiting DNA topoisomerase (topo) II or by interfering with heme
      crystallization within the parasite acidic food vacuole. Previous studies have
      shown that analogs of 9-anilinoacridine containing 3,6-diamino substitutions (in
      the acridine ring) inhibit Plasmodium falciparum DNA topo II in situ, whereas
      those with a 3,6-diCl substitution act by inhibiting beta-hematin formation, a
      property also seen with 3,6-diamino-1'-dimethyl-9-anilinoacridine (DDAA). To
      understand this seemingly anomalous property of DDAA, studies of its interaction
      with hematin and localization within the parasite food vacuole were undertaken. A
      weak interaction with hematin was demonstrated spectroscopically. Antagonism of
      DDAA inhibition of Plasmodium falciparum growth in culture by concanamycin A, a
      macrolide antibiotic inhibitor of vacuolar H(+)-ATPase derived from Streptomyces
      sp, was equivocal.

PMID- 18613538
TI  - Epidemiological aspects and risk factors of toxocariasis in a pediatric
      population in Sri Lanka.
AB  - This cross-sectional study, carried out over a period of 11 months, investigated
      the relationship between Toxocara seropositivity, socio-demographic and
      environmental variables in a pediatric population. Risk factors for Toxocara
      infection were assessed by direct interview of parent or guardian using a
      structured pre-tested questionnaire. Eosinophilia and presence of helminth eggs
      or protozoan cysts in a fecal smear were recorded. Diagnosis of Toxocara
      seropositivity in children was based on IgG Toxocara Microwell Serum Elisa Kits.
      The ELISA test was regarded as positive if the optical density was 0.3 units or
      above. Unadjusted and adjusted odds ratios were calculated to determine risk
      factors for disease. The proportion of children who were positive for Toxocara
      antibodies in the study population was 20%. Children being exposed to a puppy of
      less than 3 months at home, visiting a playground frequently, living in a poorly
      constructed house and dogs having access to playgrounds were significant risk
      factors on univariate analysis. Of these four variables, only the first three
      variables (OR 19, OR 4 and OR 3, respectively) remained significant risk factors
      on the multivariate model. Presence of eosinophilia in seropositive children was
      significantly higher than the seronegative group (77% vs 40%; p < 0.001). This
      study indicates that dogs contribute significantly to children being seropositive
      for toxocariasis in Sri Lanka. Implementation of public health programs
      specifically focused on anti-parasitic treatment of dogs is recommended.

PMID- 18613539
TI  - Restriction enzyme digestion analysis of PCR-amplified DNA of Blastocystis
      hominis isolates.
AB  - Genomic DNA of Blastocystis isolates released into 0.1% Triton X-100 was suitable
      for amplification and yielded similar results as the genomic DNA extracted with
      standard kit. The specific B. hominis primers (BH1: GCT TAT CTG GTT GAT CCT GCC
      AGT and BH2: TGA TCC TTC CGC AGG TTC ACC TAC A) successfully produced the PCR
      product of about 1,770 bp with all the 7 Blastocystis isolates tested. The
      restriction fragment length polymorphism (RFLP) patterns yielded by 13 out of 25
      restriction endonucleases showed that the 7 isolates could be grouped into 4
      subgroups: subgroup-1 consisted of isolate C; subgroup-2 of isolates H4 and H7;
      subgroup-3 of isolates KP1, Y51 and M12; and subgroup-4 of isolate 27805. The
      differences between subgroups manifested as clear-cut RFLP patterns. A common
      band of 230 bp was revealed by Eco R1 in all the Blastocystis isolates tested.
      The band of about 180 bp was revealed by Alu I, differentiated symptomatic from
      asymptomatic isolates of this parasite, and might indicate the pathogenicity of
      this parasite.

PMID- 18613540
TI  - An unceasing problem: soil-transmitted helminthiases in rural Malaysian
      communities.
AB  - Despite great development in socioeconomic status throughout 50 years of
      independence, Malaysia is still plagued with soil-transmitted helminthiases
      (STH). STH continue to have a significant impact on public health particularly in
      rural communities. In order to determine the prevalence of STH among rural Orang
      Asli children and to investigate the possible risk factors affecting the pattern
      of this prevalence, fecal samples were collected from 292 Orang Asli primary
      schoolchildren (145 males and 147 females) age 7-12 years, from Pos Betau, Kuala
      Lipis, Pahang. The samples were examined by Kato-Katz and Harada Mori techniques.
      Socioeconomic data were collected using pre-tested questionnaires. The overall
      prevalence of ascariasis, trichuriasis, and hookworm infections were 67.8, 95.5
      and 13.4%, respectively. Twenty-nine point eight percent of the children had
      heavy trichuriasis, while 22.3% had heavy ascariasis. Sixty-seven point seven
      percent of the children had mixed infections. Age > 10 years (p = 0.016), no
      toilet in the house (p = 0.012), working mother (p = 0.040), low household income
      (p = 0.033), and large family size (p = 0.028) were identified as risk factors
      for ascariasis. Logistic regression confirmed low income, no toilet in the house
      and working mother as significant risk factors for ascariasis. The prevalence of
      STH is still very high in rural Malaysian communities. STH may also contribute to
      other health problems such as micronutrient deficiencies, protein-energy
      malnutrition and poor educational achievement. Public health personnel need to
      reassess current control measures and identify innovative and integrated ways in
      order to reduce STH significantly in rural communities.

PMID- 18613541
TI  - Visceral schistosomiasis among domestic ruminants slaughtered in Wayanad, South
      India.
AB  - This short communication reports the prevalence of visceral schistosomiasis by
      worm counts from the mesentery of domestic ruminants of the hilly district of
      Wayanad, located in Kerala, one of the states in South India. We found 57.3, 50,
      and 4.7% of cattle, buffaloes and goats, respectively, had visceral
      schistosomiasis upon slaughter at a municipal slaughter house in Kalpetta. Our
      findings show that the prevalence of Schistosoma spindale infection is very high
      in Wayanad in comparison to previous reports from this and neighboring countries.

PMID- 18613542
TI  - Seasonal variation of cave-dwelling phlebotomine sandflies (Diptera:Psychodidae)
      in Phra Phothisat Cave, Saraburi Province, Thailand.
AB  - Phlebotomine sandflies are widely distributed in Thailand. In view of recent
      occurrence of indigenous cases of leishmaniasis in Thailand, a bionomic study of
      sandflies was undertaken in Phra Phothisat cave, Saraburi Province, Thailand from
      August 2005 to July 2006. The insects were collected monthly by CDC light traps
      between 06:00 PM and 06:00 AM. They were preserved in 80% alcohol and mounted
      with Hoyer's medium for species identification. A total of 5,514 sandflies were
      collected with a female:male ratio of 2.5:1. The collected sandflies belong to 13
      species in the genera Phlebotomus and Sergentomyia, namely S. silvatica (43.5%),
      S. anodontis (31.5%), S. dentata (15.3%), S. barraudi (3.3%), P. argentipes
      (2.0%), P. philippinensis gouldi (1.0%), P. stantoni (0.5%), S. gemmea (0.5%), P.
      major major (0.1%), S. perturbans (0.1%), S. iyengari (0.1%), S. bailyi (0.1%),
      and P. teshi (0.1%). The results revealed seasonal variation in sandflies with
      the highest peak in July (436 sandflies/trap-night). Some of the sandflies could
      not be identified and were assumed to be new species. Soil samples inside the
      cave were analyzed for chemical characteristics. The soil was characterized by
      moderate acidity (pH 5.8) with various amount of chemicals and nutrients.

PMID- 18613543
TI  - Trematode infections of the freshwater snail family Thiaridae in the Khek River,
      Thailand.
AB  - The freshwater snail family Thiaridae was studied at five different locations:
      water sources for the Khek River, Thailand. Snail samples were collected by hand
      using counts per unit of time sampling method between December 2004 and October
      2005. The physico-chemical quality of the water changed with the seasons and
      affected the sampling areas during both the dry season and the flood season. A
      total of 9,568 snail samples comprised of 14 species were found. These were 284
      Tarebia granifera, 24 Melanoides tuberculata, 86 Thiara scabra, 3,295
      Paracrostoma pseudosulcospira pseudosulcospira, 736 P. paludiformis paludiformis,
      3,266 P. paludiformis dubiosa, 117 P. morrisoni, 304 Brotia (Brotia) binodosa
      binodosa, 1,250 B. (Brotia) microsculpta, 146 B. (Senckenbergia) wykoffi, 1 B.
      (Brotia) pagodula, 5 B. (Brotia) binodosa spiralis, 5 B. (Brotia) insolita and 49
      B. (Brotia) manningi. The cercariae were investigated using shedding and crushing
      methods where they were categorized into two types and five species. The first
      type, Parapleurolophocercous cercariae, were comprised of Haplorchis pumilio
      Looss, 1899 and Centrocestus formosanus Nishigori, 1924. The second type,
      Xiphidiocercariae were comprised of Acanthatrium hitaense Koga, 1953,
      Loxogenoides bicolor Kaw, 1945 and Haematoloechus similis Looss, 1899. The
      cercarial infection rates in the above 5 species were 0.1% (5:9,568), 0.2%
      (15:9,568), 0.3% (24:9,568), 0.4% (37:9,568) and 0.1% (5:9,568), respectively.
      Five species of snails were susceptible to trematode infections. They were T.
      granifera, M. tuberculata, T. scabra, P. paludiformis paludiformis and B.
      (Senckenbergia) wykoffi; infections were found in 26.1% (74:284), 33.3% (8:24),
      1.2% (1:86), 0.3% (2:736) and 0.7% (1:146), respectively.

PMID- 18613544
TI  - A statistical method for forecasting demographic time series counts, with
      application to HIV/AIDS and other infectious disease mortality in southern
      Thailand.
AB  - This study investigated regional and temporal patterns of death reported from
      infectious diseases (including HIV/AIDS) in 14 provinces of southern Thailand
      over the period 1999-2004, using data obtained from the Thailand Bureau of Policy
      and Strategy, Ministry of Public Health. Causes of deaths were identified using
      the International Classification of Diseases 10th revision (ICD-10), and
      mortality incidence rates were then calculated using populations obtained from
      the 2000 population census. Poisson and negative binomial lagged observation
      driven regression models for mortality incidence were fitted to the data
      separately for HIV/ AIDS and other infectious diseases. Overall, the hospital
      mortality rates started to increase sharply in 2003 - 2004. The in-hospital
      mortality for HIV/AIDS showed peaks in urban districts and decreased from north
      to south with mortality for males approximately double that of females. For other
      infectious diseases, an upward trend in hospital mortality age 40 and over
      started in 2003-2004, particularly among persons reported as dying from
      septicemia, while showing a slightly increasing trend for other infectious
      diseases. Identifying the real cause of hospital deaths recorded as septicemia
      would substantially improve hospital mortality data quality.

PMID- 18613545
TI  - Sources of data for improved surveillance of HIV/AIDS in China.
AB  - The objective of this paper is to describe the evolution of human
      immunodeficiency virus/acquired immunodeficiency syndrome surveillance in
      mainland China, with a focus on reviewing the sources of data being used for
      improved surveillance of HIV/AIDS. We review the development of HIV/AIDS
      surveillance and its multiple data sources to monitor the dynamics of HIV/AIDS in
      China. The surveillance system for HIV/AIDS in China was initiated in 1986. It
      has evolved in three stages: (1) passive surveillance, (2) HIV sentinel
      surveillance with coexisting active surveillance and passive surveillance, and
      (3) comprehensive surveillance. In parallel with the evolution of the
      surveillance system itself, the HIV epidemic in China has gone through increasing
      stages of complexity, through an Introduction Phase, a Spreading Phase, and a
      Rapidy Spreading Phase. More reliable data from improved surveillance suggest
      that the HIV/AIDS epidemic is expanding in China. HIV infections among 2005
      estimates remain concentrated among injection drug users (IDUs), those buying and
      selling sex, and men who have sex with men. Better HIV/AIDS surveillance
      synthesizes multiple data sources to provide a more accurate picture of the
      dynamics of specific HIV/AIDS circumstances in different areas of China. Improved
      surveillance is meaningful insofar as data are used to implement more effective
      HIV prevention programs in China. Support for surveillance and strategic analyses
      can enable policy decision makers to make more effective program choices and
      mobilize adequate resources to contain HIV.

PMID- 18613546
TI  - Outcomes in HIV-infected patients on antiretroviral therapy with tuberculosis.
AB  - HIV-infected patients with active tuberculosis (TB) having CD4 counts < 100/mm3
      and who were antiretroviral therapy (ART) naive were reviewed retrospectively to
      determine the outcomes of their tuberculosis infection. All patients received ART
      at or after receiving anti-TB treatment. Clinical manifestations, treatment
      regimens and outcomes were analyzed. Of 101 patients, 62 (61.4%) completed TB
      treatment. Of these, 53.2% were treated with a 6-month standard TB regimen, while
      the rest were treated with prolonged TB regimens. The median interval between
      anti-TB treatment and ART was 68 days (range: 0-381). Among the clinically cured
      patients 66.1% received rifampin concomitantly with nevirapine, and 32.3%
      received rifampin concomitantly with efavirenz. The treatment success rate was
      75.6%, with a mortality rate of 6.1%. The risk factors for death were resistant
      TB (p = 0.03) and poor compliance (p < 0.05). Seven point nine percent had multi
      drug resistant TB. Possible or probable immune reconstitution inflammatory
      syndrome (IRIS) was seen in 15 cases (14.9%). No life-threatening IRIS was
      reported, and it did not affect disease outcome (p = 0.5). A shorter time between
      anti-TB treatment and ART onset was associated with the occurrence of IRIS (31
      days vs 90 days; p < 0.05). Regarding adverse drug effects, 44.6% had side
      effects due either to anti-TB drugs or ART. Sixty-six point one percent of them
      occurred within the first 2 months of TB treatment, and 43 (76.8%) had to stop or
      change either anti-TB treatment or ART. The mortality rate with TB and HIV on ART
      was low and the occurrence of IRIS did not carry any additional mortality.

PMID- 18613547
TI  - Sexual behavior and HIV infection among pregnant hilltribe women in northern
      Thailand.
AB  - A case-control study was carried out to determine factors associated with HIV
      infection among pregnant hilltribe women who attended the antenatal clinics of
      six hospitals in northern Thailand (Mae Suai, Wieng Pa Pao, Mae Sai, Mae Chan,
      Wieng Kaen, Mae Fa Luang, and Chiang Rai hospitals) between 1 January 2005- 31
      May 2007. Data were collected using questionnaires and analysis was by univariate
      (p-value = 0.100) and multivariate analysis (p-value = 0.050) in the model of
      unconditional multiple logistic regression. The ratio of cases to controls was
      1:4. The sample consisted of 255 subjects; 51 cases and 204 controls. The mean
      age of the women was 26.9 years (min = 15, max = 52, and SD 7.3). The majority of
      the women were Lahu (49.8%) or Akha (36.9%). Nearly half the women were Christian
      (48.2%), followed by Buddhist (42.4%). Most of the women were not educated
      (60.4%). The largest group for family income was 10,000-49,999 baht/year (62.6%).
      After controlling for family income, family debt, education, occupation and
      household members, the findings showed that the "not married to debut partner"
      group were at greater risk than the "married to debut partner" group by 6.6 times
      (OR(adj) = 6.6, 95% CI = 2.9-14.9). The "use of alcohol" group were at higher
      risk by 4.5 times (OR(adj) = 4.5, 95% CI = 2.0-10.3) compared to the no alcohol
      use group, and a history of genital ulcer group had an increased risk of 6.3
      times (OR(adj) = 6.3, 95% CI = 1.2-31.1) the chance of having HIV infection
      compared to no history of genital ulcers in pregnant hilltribe women.

PMID- 18613548
TI  - Trends in hepatitis B virus infection among blood donors in Kelantan, Malaysia: a
      retrospective study.
AB  - The objective of this study was to determine the prevalence and trends in
      hepatitis B infection among blood donors attending the Transfusion Medicine Unit
      at the Hospital Universiti Sains Malaysia, Kelantan, Malaysia. A retrospective
      study was carried out by reviewing the results of HBsAg among blood donors for
      the years 2000 to 2004. During this period, 44,658 blood donors were studied. We
      noted that there was a significant difference in the prevalence of hepatitis B
      infection between regular and first time donors. There was also a decreasing
      trend noticed in both study groups. The mean prevalence was significantly
      different between first time (1.83%) and regular donors (0.45%) (p < 0.005).
      There is a need to improve public awareness programs to lower the incidence of
      hepatitis B infection in the general population and consequently first time blood
      donors. Future studies are also required to determine the trends and outcomes of
      these programs.

PMID- 18613549
TI  - Household and community transmission of the Asian influenza A (H2N2) and
      influenza B viruses in 1957 and 1961.
AB  - This study analyzed the distribution of the number of cases in households of
      various sizes, reconsidering previous survey data from the Asian influenza A
      (H2N2) pandemic in 1957 and the influenza B epidemic in 1961. The final size
      distributions for the number of household cases were extracted from four
      different data sources (n = 547, 671, 92 and 263 households), and a probability
      model was applied to estimate the community probability of infection (CPI) and
      household secondary attack rate (SAR). For the 1957 Asian influenza pandemic, the
      CPI and household SAR were estimated to be 0.42 [95% confidence intervals (CI):
      0.37, 0.47] and 7.06% (95% CI: 4.73, 9.44), respectively, using data from Tokyo.
      The figures for the same pandemic using data from Osaka were 0.21 (95% CI: 0.19,
      0.22) and 9.07% (95% CI: 6.73, 11.53), respectively. Similarly, the CPI and
      household SAR for two different datasets of influenza B epidemics in Osaka in
      1961 were estimated as 0.37 (95% CI: 0.30, 0.44) and 18.41% (95% CI: 11.37,
      25.95) and 0.20 (95% CI: 0.13, 0.28) and 10.51% (95% CI: 8.01, 13.15),
      respectively. Community transmission was more frequent than household
      transmission, both for the Asian influenza pandemic and the influenza B epidemic,
      implying that community-based countermeasures (eg, area quarantine and social
      distancing) may play key roles in influenza interventions.

PMID- 18613550
TI  - Myalgia Cruris Epidemica: an unusual presentation of dengue fever.
AB  - We describe a 5-year-old girl who had sudden onset difficulty in walking after 3
      days of febrile illness. In the emergency department her creatine kinase level
      was elevated but urine myoglobin was normal. She was diagnosed as having benign
      acute childhood myositis. Because of poor oral intake and dehydration, she was
      admitted to the pediatric ward. The next day she had a petechial rash over the
      antecubital fossa, and dengue IgM back was positive. She was treated
      conservatively and recovered uneventfully. Despite dengue fever being endemic in
      Malaysia, this is the first case report of myositis following dengue infection in
      Malaysia.

PMID- 18613551
TI  - Serovar distribution and antibiotic susceptibility of nontyphoidal Salmonella
      isolated from pediatric patients in Jakarta, Indonesia.
AB  - A study was conducted during January 2003 through August 2005, at two community
      health centers in south Jakarta, Indonesia, to detect nontyphoidal Salmonella
      infections in children with diarrhea. A total of 814 rectal swab samples were
      collected, of which 56 (6.9%) were positive for Salmonella. Among the serovars
      detected, Salmonella enterica serovar Typhimurium was found most frequently in
      32.1% of all Salmonella isolates. Antimicrobial susceptibility testing using
      eight antibiotics showed 5.6% to 66.7% of Salmonella serovars resistant to
      ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, and
      nalidixic acid. However, all serovars were susceptible to norfloxacin,
      ciprofloxacin, and ceftriaxone.

PMID- 18613552
TI  - Analysis of gyrA mutations related to quinolone resistance in Escherichia coli
      isolates originating from pet, human, vegetable and ice in Bangkok and vicinity.
AB  - Escherichia coli was used to investigate quinolone resistance and mutations in
      gyrA gene of E. coli isolated from pet (dog and cat), human (pet's owner),
      vegetable and edible ice in Bangkok and vicinity. Susceptibility test for
      nalidixic acid (NA) showed similar percent resistance among the sample sources
      but a lower ciprofloxacin (CIP) resistance was found particularly in human
      source. Mutations within quinolone resistance determining region of gyrA gene
      analyzed using non-radioactive single-strand conformation polymorphism (SSCP) and
      sequencing showed 10 different SSCP patterns. E. coli isolates from pet,
      vegetable and ice showed more variety of patterns than strains isolated from
      human. Four out of 10 SSCP patterns were identified as having mutations in amino
      acids positions 83 (Ser to Leu) and position 87 (Asp to Asn). These mutations
      were observed only in NA-resistant strains and combined mutations were observed
      only in E. coli isolated from humans and pets. As only 24% of NA- and CIP
      resistant E coli isolates contained gyrA mutations, other quinolone resistant
      mechanisms may be involved. Nevertheless, gyrA mutations may be used to monitor
      nalidixid acid resistance in E. coli.

PMID- 18613553
TI  - Helicobacter pylori infection in peptic ulcer disease: the importance of smoking
      and ethnicity.
AB  - This study was conducted to determine the prevalence of Helicobacter pylori (H.
      pylori) and its associated factors among patients with peptic ulcer disease in
      Taiping Hospital. Consecutive peptic ulcer disease patients who had undergone
      esophagogastro-duodenoscopy were included. The H. pylori status was assessed by
      the rapid urease test. We excluded those who had active bleeding, a perforated
      peptic ulcer, severe vomiting, a history of gastric surgery, peptic ulcer disease
      or renal or liver diseases, carcinoma of the stomach, and recent use of
      antibiotics or proton pump inhibitors. Socio-demography, H. pylori status,
      medication history and other relevant clinical data were collected from case
      notes. A total of 416 subjects were selected, 49.7% were positive and 50.3% were
      negative for H. pylori infection. There were significant associations between H.
      pylori and age, ethnicity, smoking status and NSAID usage. However, there were no
      significant relationships between H. pylori status and gender or type of peptic
      ulcer. Multiple logistic regression showed that other ethnicities than Malays and
      smokers had a higher risk of H. pylori. Our prevalence rate was low and the
      identified risk factors were consistent with previous studies. Ethnic differences
      may be related to genetic and sociocultural behaviors. Quitting smoking may
      benefit peptic ulcer patients with H. pylori infection.

PMID- 18613554
TI  - Comparison of a slide agglutination test, LeptoTek Dri-Dot, and IgM-ELISA with
      microscopic agglutination test for Leptospira antibody detection.
AB  - A slide agglutination test (SAT), LeptoTek Dri-Dot and IgM-ELISA were compared
      with a microscopic agglutination test (MAT) for the detection of Leptospira
      antibodies. Paired sera from 10 patients whose leptospirosis was clinically
      suspected and diagnosed by MAT, were evaluated in this study. Our data,
      especially from acute samples, demonstrate the SAT and Dri-Dot were more
      sensitive as initial screening tests than MAT. IgM-ELISA has an advantage over
      MAT, SAT, and Dri-Dot since the results can be interpreted from a single serum
      testing if the results of the test are positive. Eight of the ten cases could be
      diagnosed by IgM-ELISA. Our data suggest that IgM-ELISA may be used for the
      diagnosis of leptospirosis. However, the agglutination test is useful for
      screening and for secondary infection cases for which IgM antibodies may be
      undetectable. MAT can be performed as a reference test and when information
      regarding the causative serovar is required.

PMID- 18613555
TI  - Human plague outbreak in two villages, Yunnan Province, China, 2005.
AB  - Plague is still a serious public health problem in Asia. On July 5, 2005, a
      suspected outbreak of human plague in two Chinese villages was reported to Yunnan
      Institute of Endemic Disease Control and Prevention (YIEDC). Active case finding,
      laboratory investigation, environmental inspection, and control measures were
      conducted by provincial and local health authorities. A suspected case was an
      individual who resided in one of the two villages and developed fever and painful
      swollen lymph nodes in the groin, axilla, and neck between June 26 and July 11,
      2005. Confirmation was by indirect hemagglutination test (IHA) for plague F1
      antibody. A confirmed animal plague case was an animal that tested positive for
      one of the following tests: IIA, reverse indirect hemagglutination, or bacterial
      culture. There were three confirmed and one suspected case of human plague. Of
      nine retrieved rats, three were confirmed cases. Most surveyed houses had poor
      sanitation, and there was a history of dead rats observed in the villages. After
      control measures were implemented, the rat density and flea index decreased to
      acceptable levels and no new cases occurred. The cause of this outbreak was
      likely due to rat die off in the villages, such that rat flea populations
      migrated to humans under environmentally favorable conditions. The outbreak was
      controlled after implementing environmental and educational control measures.

PMID- 18613556
TI  - A preliminary study of thiamine status in northeastern Thai children with acute
      diarrhea.
AB  - This study is a preliminary determination of thiamine status in children with
      diarrhea and metabolic acidosis admitted to hospital. Children with diarrhea (N =
      14; age 2 m-6 yr) were divided into 2 groups according to anion gap type; group 1
      (21.4%) with a normal anion gap (5.5 +/- 5.2 mmol/l) and group 2 (78.6%) with a
      wide anion gap (21.2 +/- 5.2 mmol/l). Blood was taken on the day of admission to
      determine thiamine and lactate levels. Sixty-six point seven percent of patients
      in group 1 had a normal lactate level (1.5 +/- 0.8 mmol/l) and 33.3% had a high
      lactate level (2.2 mmol/l); none had thiamine deficiency (TPPE < 20%). High
      lactate (3.5 +/- 1.4 mmol/l) was found in 54.5% of group 2 and thiamine
      deficiency was observed in 18.2% of this group. In conclusion, no thiamine
      deficiency was noted in patients with normal anion gap, but thiamine deficiency
      was not uncommon in patients with a wide anion gap, regardless of lactic
      acidosis.

PMID- 18613557
TI  - The use of an In House Scoring System Scale versus Glasgow Coma Scale in non
      traumatic altered states of consciousness patients: can it be used for triaging
      patients in Southeast Asian developing countries?
AB  - Non-traumatic Altered States of Consciousness (ASC) are a non-specific
      consequence of various etiologies, and are normally monitored by Glasgow Coma
      Scale (GCS). The GCS gives varriable results among untrained emergency medicine
      personel in developing countries where English is not the first language. An In
      House Scoring System (IHSS) scale was made by the first author for the purpose of
      triaging so as to quickly asses patients when seen by medical personel. This IHSS
      scale was compared to the GCS to determine it's specificity and sensitivity in
      the accident and emergency department (ED) of Hospital University Sains Malaysia
      (HUSM). All patients with non-traumatic ASC were selected by purposive sampling
      according to pre-determined criteria. Patients were evaluated by the two systems,
      IHSS and GCS, by emergency physicians who were on call. Patient demographics,
      clinical features, investigations, treatment given and outcomes were collected
      and followed for a period of 14 days. A total of 221 patients with non-traumatic
      ASC were studied, 54.3% were males. The mean age of the patients was 56 years
      old. The mean overall GCS score on presentation to the ED was 10.3. The mean
      duration of ASC was 11.6 hours. One hundred thirty patients (58.8%) experienced
      ASC secondary to general or focal cerebral disorders. The mortality rate was
      40.3% 2 weeks after the ED visit. Fifty-four point three percent of the patients
      were awake and considered to have good outcomes while 45.7% of the patients had
      poor outcomes (comatose or dead) 2 weeks after the ED visit. The mean overall GCS
      score, verbal and motor subscores as well as the IHSS had significantly decreased
      (worsened) after treatment in the ED. A poor IHSS scale, hypertension, current
      smoking, abnormal pupillary reflexes and acidosis were associated with a worse 2
      week outcome. The mean age and WBC count was lower and the mean overall GCS score
      and eye, verbal and motor subscores were higher as well as those having a lower
      IHSS scale for the good outcome category. Multivariate analysis revealed that
      smokers and hypertensives were at higher risk for a poor outcome. Higher eye
      scores on the GCS were associated fewer poor outcomes. There was significant
      agreement between the IHSS scale and GCS scores in the assessment of non
      traumatic ASC. The sensitivity and specificity of the IHSS score versus GCS were
      71.9% and 100.0%, respectively.

PMID- 18613558
TI  - Establishment and evaluation of the Japanese edition of the Weekly
      Epidemiological Record (WER) website by the Faculty of Health Sciences of Kobe
      University School of Medicine.
AB  - To report on the establishment of the Japanese version website of the Weekly
      Epidemiological Record (WER) by the faculty and to evaluate its accessibility and
      the educational outcome: all articles from the WER since 2000 have been
      translated into Japanese by graduate students with teachers' guidance, verified
      by the committee members, and delivered to the website. The server log files and
      retrieval keywords were analyzed using Analog 6.0. An on-line questionnaire
      survey of visitors to the website was performed. Opinion sheets reported by the
      students for translation were evaluated as the educational outcome. Over 6 years,
      there were 820,571 requests to the website and, the number of requests increased
      with disease outbreaks. According to domain analysis, most requests were during
      daytime on weekdays, and the website was utilized by users in educational
      institutions and the Japanese government and by overseas visitors. Among
      respondents to the questionnaire, 47% were laypersons and 69% found the website
      easy to understand. SARS and HIV/AIDS were the terms most frequently used for
      retrieval. The students recognized the importance of the World Health
      Organization (WHO) and had broadened their perspective on international health.
      The website is useful for Japanese. The translating process was effective for
      international health education.

PMID- 18613559
TI  - The use of herbal medicines during pregnancy and perinatal mortality in Tumpat
      District, Kelantan, Malaysia.
AB  - The objective of this case-control study was to determine the association between
      herbal medicine use during pregnancy and perinatal mortality in Tumpat District,
      Kelantan, Malaysia. Cases were mothers who gave birth from June 2002 to June 2005
      with a history of perinatal mortality, while controls were those without a
      history of perinatal infant mortality. A total of 316 mothers (106 cases and 210
      controls) were interviewed. The use of unidentified herbs prepared by traditional
      midwives and other types of herbal medicines during the first trimester of
      pregnancy were positively associated with perinatal mortality (OR = 5.24, 95% CI
      = 1.13; 24.23 and OR = 8.90, 95%, CI = 1.35; 58.53, respectively). The use of
      unidentified "Orang Asli" herbs and coconut oil during the third trimester of
      pregnancy were negatively associated with perinatal mortality in Tumpat (OR =
      0.10, 95% CI = 0.02; 0.59 and OR = 0.48, 95% CI = 0.25; 0.92, respectively).
      These findings suggest the use of unidentified "Orang Asli" herbs and coconut oil
      in late pregnancy are protective against perinatal mortality, while the use of
      unidentified herbs prepared by traditional midwives and other types of herbal
      medicines in early pregnancy has an increased risk of perinatal infant mortality.
      Pharmacological studies to confirm and identify the compounds in these herbs and
      their effects on the fetus should be conducted in the future.

PMID- 18613560
TI  - Self-reported health benefits in patients recruited into New Zealand's 'Green
      Prescription' primary health care program.
AB  - To assess the effectiveness of the 'Green Prescription' (GRx) program in
      promoting self-reported health benefits in previously inactive individuals,
      between 2001 and 2002, a retrospective survey was administered to 124 GRx
      patients throughout New Zealand. Participants were a non-randomized subset of a
      larger GRx population. Logistic regression was used to calculate odds ratios (OR)
      and 95% confidence intervals (CI) for differences in health outcomes between
      participants who had increased physical activity levels compared to participants
      who had decreased or not altered activity levels since first being prescribed the
      GRx. Completed surveys were obtained from 124 of 263 eligible participants; a
      response rate of 47%. Fifty-six percent of participants reported increases in
      physical activity levels after the GRx program, with 70% still undertaking some
      form of physical activity. Participants accumulated at least 30 minutes of
      physical activity per day on 3.4 +/- 2.5 days (mean +/- SD) per week.
      Participants who reported increased physical activity levels after the GRx
      reported substantially higher energy levels and improved breathing when compared
      to participants who reported less or about the same physical activity after the
      GRx intervention. Increased physical activity in GRx patients was associated with
      greater perceived health benefits. Effective and ongoing support networks were
      seen as important for behavior change.

PMID- 18613561
TI  - Foraging and nesting behavior of Osmia lignaria (Hymenoptera: Megachilidae) in
      the presence of fungicides: cage studies.
AB  - During orchard pollination studies in California, we observed dramatic changes in
      nesting and foraging behavior of Osmia lignaria Say (Hymenoptera: Megachilidae)
      after sprays with tank mixtures containing fungicides. A characteristic pattern
      of postspray events observed includes erratic behavior and interrupted foraging
      and nesting activity for several days. In an effort to determine whether
      fungicidal sprays were disruptive to bee foraging and thus to pollination, we
      exposed O. lignaria females nesting in field cages planted with lacy
      scorpionweed, Phacelia tanacetifolia Benth (Hydrophyllaceae), to selected spray
      mixtures normally encountered in California orchard production systems: iprodione
      (Rovral), propiconazole (Orbit), benomyl (Benlate), and captan (Captan 50 WP);
      the surfactant Dyne-Amic, alone and mixed with Rovral; and the tank mixture IDB
      (Rovral + Dyne-Amic + the foliar fertilizer Bayfolan Plus). An additional cage
      sprayed with an equal volume of water acted as control, and a cage sprayed with
      the insecticide dimethoate as a toxic standard. For each female O. lignaria, we
      recorded time spent inside the nest depositing pollen-nectar loads, foraging
      time, cell production rate, and survival. All females in the dimethoate treatment
      died postspray + 1 d. Before death, some of these females behaved similarly to
      our previous orchard observations. A high proportion of females in the IDB cage
      were inactive for a few hours before resuming normal foraging and nesting
      activity. No lethal or behavioral effects were found for any of the other
      compounds or mixtures tested. Our results indicate that the fungicide
      applications that we tested are compatible with the use of O. lignaria as an
      orchard pollinator.

PMID- 18613562
TI  - Comparative performance of two mite-resistant stocks of honey bees (Hymenoptera:
      Apidae) in Alabama beekeeping operations.
AB  - The utility of USDA-developed Russian and varroa sensitive hygiene (VSH) honey
      bees, Apis mellifera L. (Hymenoptera: Apidae), was compared with that of locally
      produced, commercial Italian bees during 2004-2006 in beekeeping operations in
      Alabama, USA. Infestations of varroa mites, Varroa destructor Anderson & Truman
      (Acari: Varroidae), were measured twice each year, and colonies that reached
      established economic treatment thresholds (one mite per 100 adult bees in late
      winter; 5-10 mites per 100 adult bees in late summer) were treated with
      acaricides. Infestations of tracheal mites, Acarapis woodi (Rennie) (Acari:
      Tarsonemidae), were measured autumn and compared with a treatment threshold of
      20% mite prevalence. Honey production was measured in 2005 and 2006 for colonies
      that retained original test queens. Throughout the three seasons of measurement,
      resistant stocks required less treatment against parasitic mites than the Italian
      stock. The total percentages of colonies needing treatment against varroa mites
      were 12% of VSH, 24% of Russian, and 40% of Italian. The total percentages
      requiring treatment against tracheal mites were 1% of Russian, 8% of VSH and 12%
      of Italian. The average honey yield of Russian and VSH colonies was comparable
      with that of Italian colonies each year. Beekeepers did not report any
      significant behavioral problems with the resistant stocks. These stocks thus have
      good potential for use in nonmigratory beekeeping operations in the southeastern
      United States.

PMID- 18613563
TI  - Laboratory bioassays to evaluate fungicides for chalkbrood control in larvae of
      the alfalfa leafcutting bee (Hymenoptera: Megachilidae).
AB  - Chalkbrood, a fungal disease in bees, is caused by several species of
      Ascosphaera. A. aggregata is a major mortality factor in populations of the
      alfalfa leafcutting bee, Megachile rotundata (F.) (Hymenoptera: Megachilidae)
      used in commercial alfalfa seed production. Four formulated fungicides, Benlate
      50 WP, Captan, Orbit, and Rovral 50 WP were tested in the laboratory for efficacy
      against hyphal growth of A. aggregata cultures. The same fungicides, with the
      addition of Rovral 4 F, were tested for their effects on incidence of chalkbrood
      disease, and toxicity to M. rotundata larvae. Benlate, Rovral 50 WP, and Rovral 4
      F reduced incidence of chalkbrood with minimal mortality on larval bees. Benlate
      and Rovral 50 WP also reduced hyphal growth. Orbit was effective in reducing
      hyphal growth, but it did not reduce incidence of chalkbrood and was toxic to bee
      larvae. Captan was not effective in reducing hyphal growth or chalkbrood
      incidence, and it was toxic to bee larvae. Fungicides that reduce incidence of
      chalkbrood and larval mortality in this laboratory study are candidates for
      further study for chalkbrood control.

PMID- 18613564
TI  - What's in that package? An evaluation of quality of package honey bee
      (Hymenoptera: Apidae) shipments in the United States.
AB  - To replace deceased colonies or to increase the colony numbers, beekeepers often
      purchase honey bees, Apis mellifera L., in a package, which is composed of 909
      1,364 g (2-3 lb) of worker bees and a mated queen. Packages are typically
      produced in warm regions of the United States in spring and shipped throughout
      the United States to replace colonies that perished during winter. Although the
      package bee industry is effective in replacing colonies lost in winter, packages
      also can be an effective means of dispersing diseases, parasites, and undesirable
      stock to beekeepers throughout the United States. To evaluate the quality of
      packages, we examined 48 packages representing six lines of bees purchased in the
      spring 2006. We estimated levels of the parasitic mite Varroa destructor Anderson
      & Trueman and the percentage of drone (male) honey bees received in packages. We
      surveyed for presence of the tracheal honey bee mite, Acarapis woodi (Rennie),
      and a microsporidian parasite, Nosema spp., in the shipped bees. We found
      significant differences in both the mean Varroa mite per bee ratios (0.004-0.054)
      and the average percentage of drones (0.04-5.1%) in packages from different
      producers. We found significant differences in the number of Nosema-infected
      packages (0.0-75.0%) among the six lines. No packages contained detectable levels
      ofA. woodi. Considering the observed variability among honey bee packages,
      beekeepers should be aware of the potential for pest and disease infestations and
      high drone levels in packages.

PMID- 18613565
TI  - Do weather conditions correlate with findings in failed, provision-filled nest
      cells of Megachile rotundata (Hymenoptera: Megachilidae) in western North
      America?
AB  - Cavity-nesting alfalfa leafcutting bees, Megachile rotundata (F.) (Hymenoptera:
      Megachilidae), are excellent pollinators of alfalfa, Medicago savita L., for seed
      production. In commercial settings, artificial cavities are placed in field
      domiciles for nesting and, thereby, bee populations are sustained for future use.
      For this study, cells from leafcutting bee nests were collected in late summer
      from commercial seed fields. Over 3 yr (2003-2005), 39 samples in total of
      approximately equal to 1,000 cells each were taken from several northwestern U.S.
      states and from Manitoba, Canada. X-radiography of 500 cells from each sample was
      used to identify "pollen balls" (i.e., cells in which the pollen-nectar provision
      remained, but the egg or larva, if present, was not detectable on an x
      radiograph). Most U.S. samples seemed to have higher proportions of pollen ball
      cells than Manitoba samples. Pollen ball cells were dissected to determine the
      moisture condition of the mass provision and true contents of each cell. Most
      pollen ball cells from Manitoba samples contained fungus, the frequency of which
      was positively correlated with cool, wet weather. In the United States, most
      pollen ball cells had moist provisions, and many of them lacked young brood.
      Correlation analysis revealed that pollen ball cells occurred in greater
      proportions in fields with more hot days (above 38 degrees C). Broodless pollen
      ball cells occurred in greater proportions under cool conditions, but dead small
      larvae (second-third instars) seemed to occur in greater proportions under hot
      conditions. Pollen ball cells with unhatched eggs and first instars (in the
      chorion) occurred in lesser proportions under hot conditions.

PMID- 18613566
TI  - Establishment of Cotesia flavipes (Hymenoptera: Braconidae) in sugarcane fields
      of Ethiopia and origin of founding population.
AB  - Cotesia flavipes (Cameron) (Hymenoptera: Braconidae) is used as a classical
      biological control agent against Chilo partellus (Swinhoe) (Lepidoptera:
      Crambidae), a serious exotic pest of cereal crops in eastern and southern Africa.
      This parasitoid has been introduced into several African countries for the
      control of C. partellus in maize, Zea mays L., and sorghum, Sorghum bicolor (L.),
      but it has never been released in Ethiopia. It is hypothesized that it spread
      into Ethiopia from populations released in Kenya and Somalia to become the
      predominant parasitoid of C. partellus in maize and sorghum fields of the
      country. In recent surveys conducted in Ethiopia, C. flavipes was recovered from
      C. partellus in sugarcane, Saccharum L. spp. hybrids, at a site >2,000 km from
      the nearest known release sites in Kenya and Somalia. These findings question
      published hypotheses that estimate the dispersal rate of C. flavipes to be 60 km
      per year in Africa, and they suggest that since its release in Africa this
      parasitoid has developed strains adapted to searching particular host plants
      infested by particular stem borers. The anomalies between our results and
      previous reports evoked the hypothesis that C. flavipes in Ethiopian sugarcane
      might be a different strain. To test this hypothesis, we compared partial COI
      gene sequences of C. flavipes collected from sugarcane in Ethiopia and those of
      specimens from other African countries to determine the origin of the Ethiopian
      population. In addition, COI sequences were obtained for C. flavipes from other
      continents. The C. flavipes population established in Ethiopian sugarcane is most
      closely related to the populations released against C. partellus in maize in
      other parts of Africa, which were derived from the original population imported
      from Pakistan. The dispersal rate of the parasitoid was estimated to be >200 km
      per year.

PMID- 18613567
TI  - Bioecology of Stenoma catenifer (Lepidoptera: Elachistidae) and associated larval
      parasitoids reared from Hass avocados in Guatemala.
AB  - A 10-wk study of the avocado seed-feeding moth Stenoma catenifer Walsingham
      (Lepidoptera: Elachistidae), was conducted in a commercial 'Hass' avocado (Persea
      americana Miller [Lauraceae]) orchard in Guatemala. Up to 45% of fruit in the
      orchard were damaged by larval S. catenifer. Larval-to-adult survivorship for
      1,881 S. catenifer larvae in Hass fruit was 37%, and adult sex ratio was 51%
      female. Four species of larval parasitoid were reared from field-collected S.
      catenifer larvae. The most common parasitoid reared was a gregarious Apanteles
      sp., which parasitized 53% of larvae and produced on average eight to nine
      cocoons per host. Apanteles sp. sex ratio was 47% female and 87% of parasitoids
      emerged successfully from cocoons. Apanteles sp. longevity was approximately
      equal to 1.5 d in the absence of food, and when provisioned with honey,
      parasitoids survived for 5-7 d. The mean number of cocoons produced by Apanteles
      sp. per host, and larval parasitism rates were not significantly affected by the
      number of S. catenifer larvae inhabiting seeds. Oviposition studies conducted
      with S. catenifer in the laboratory indicated that this moth lays significantly
      more eggs on the branch to which the fruit pedicel is attached than on avocado
      fruit. When given a choice between Hass and non-Hass avocados, S. catenifer lays
      up to 2.69 times more eggs on Hass.

PMID- 18613568
TI  - Testing baits to control Argentine ants (Hymenoptera: Formicidae) in vineyards.
AB  - Liquid baits were evaluated for control of the Argentine ant, Linepithema humile
      (Mayr) (Hymenoptera: Formicidae), and associated mealybug and soft scale pests in
      California vineyards. In 2003, liquid baits with small doses ofimidacloprid,
      boric acid, or thiamethoxam dissolved in 25% sucrose water resulted in lower ant
      and mealybug densities and fruit damage, compared with an untreated control.
      Similar treatments in a soft scale-infested vineyard showed only a reduction of
      ant density and fruit infestation in only the boric acid and thiamethoxam
      treatments. In 2004, commercial and noncommercial formulations of liquid baits
      reduced ant densities in three separate trials, but they had inconsistent effects
      on mealybug densities and fruit infestation; granular protein bait had no effect.
      Using large plots and commercial application methodologies, liquid bait deployed
      in June resulted in lower ant density and fruit infestation, but it had no effect
      on mealybug density. Across all trials, liquid bait treatments resulted in lower
      ant density (12 of 14 trials) and fruit damage (11 of 14 sites), presenting the
      first report of liquid baits applied using commercial methodologies that resulted
      in a reduction of ants and their associated hemipteran crop damage. For
      commercialization of liquid baits, we showed that any of the tested insecticides
      can suppress Argentine ants when properly delivered in the crop system. For
      imidacloprid, bait dispensers must be protected from sunlight to reduce
      photodegradation. Results suggest that incomplete ant suppression can suppress
      mealybug densities. However, after ant populations are suppressed, there may be a
      longer period before hemipteran populations are effectively suppressed.
      Therefore, liquid baits should be considered part of a multiseason program rather
      than a direct, in-season control of hemipteran pest populations.

PMID- 18613569
TI  - Effect of irradiation on Mexican leafroller (Lepidoptera: Tortricidae)
      development and reproduction.
AB  - The effects of irradiation on egg, larval, and pupal development, and adult
      reproduction in Mexican leafroller, Amorbia emigratella Busck (Lepidoptera:
      Tortricidae), were examined. Eggs, neonates, early instars, late instars, early
      pupae, and late pupae were irradiated at target doses of 60, 90, 120, or 150 Gy,
      or they were left untreated as controls in replicated factorial experiments.
      Survival to the adult stage was recorded. Tolerance to radiation increased with
      increasing age and developmental stage. A radiation dose of 90 Gy applied to
      neonates and early instars prevented adult emergence. A dose of 150 Gy was not
      sufficient to prevent adult emergence in late instars or pupae. The effect of
      irradiation on sterility was examined in late pupae and adult moths. For progeny
      produced by insects treated as late pupae, a total of three out of 3,130 eggs
      hatched at 90 Gy, 0 out of 2,900 eggs hatched at 120 Gy, and 0 out of 1,700 eggs
      hatched at 150 Gy. From regression analysis, the dose predicted to prevent egg
      hatch from the progeny of irradiated late pupae was 120 Gy, with a 95% confidence
      interval of 101-149 Gy. The late pupa is the most radiotolerant stage likely to
      occur with exported commodities; therefore, a minimum absorbed radiation dose of
      149 Gy (nominally 150 Gy) has potential as a quarantine treatment. Reciprocal
      crosses between irradiated and unirradiated moths demonstrated that males were
      more radiotolerant than females. Irradiation of female moths at a target dose of
      90 Gy before pairing and mating with irradiated or unirradiated males resulted in
      no viable eggs, whereas irradiated males paired with unirradiated females
      produced viable eggs at 90 and 150 Gy.

PMID- 18613570
TI  - Potential increase in fruit fly (Diptera: Tephritidae) interceptions using
      ionizing irradiation phytosanitary treatments.
AB  - Irradiation postharvest phytosanitary treatments are used increasingly and show
      further promise because of advantages compared with other treatments. Its chief
      disadvantage is that, unlike all other commercially used treatments, it does not
      provide acute mortality, although it prevents insects from completing development
      or reproducing. The objective of this research was to determine to what extent
      irradiated egg and early instars of tephritids would develop to later instars
      that could be found by phytosanitary inspectors or consumers. Mexican fruit fly,
      Anastrepha ludens (Loew), eggs and first instars in grapefruit, Citrus paradisi
      Macfayden, were irradiated with 70-250 Gy and held at approximately equal to 27
      degrees C until third instars completed development. The accepted minimum
      absorbed phytosanitary dose for this pest is 70 Gy, although higher doses may be
      applied under commercial conditions. The more developed a fruit fly before it was
      irradiated, the greater the proportion that survived to the third instar. Also,
      dose was inversely related to developmental success, e.g., a mean of
      approximately 65 and 35%, respectively, of late first instars reached the third
      instar when irradiated with 70 and 250 Gy. Of those, 65.1 and 23.4%,
      respectively, pupariated, although no adults emerged. Irradiation may result in a
      greater frequency of live (albeit incapable of resulting in an infestation)
      larvae being found than would be expected compared with other treatments that
      provide acute mortality. The regulatory community should be aware of this and the
      fact that it does not increase the risk of irradiation phytosanitary treatments
      resulting in an infestation of quarantine pests.

PMID- 18613571
TI  - Floral scent of Canada thistle and its potential as a generic insect attractant.
AB  - The flowers of Canada thistle, Cirsium arvense (L.), attract a wide range of
      insects, including pollinators and herbivorous species. This attraction is
      primarily mediated by floral odor, which offers potential for developing generic
      insect attractants based on odor. In this study, we have analyzed the chemical
      composition of the volatiles produced by Canada thistle flowers. Nineteen floral
      compounds were identified in the headspace, including phenylacetaldehyde (55%),
      methyl salicylate (14%), dimethyl salicylate (8%), pyranoid linalool oxide
      (4.5%), and benzaldehyde (3.5%). Other minor compounds include benzyl alcohol,
      methylbenzoate, linalool, phenylethyl alcohol, furanoid linalool oxide, p
      anisaldehyde, 2,6-dimethyl-1,3,5,7-octatetraene, benzylacetate, benzyl tiglate,
      (E,E)-alpha-farnesene, benzyl benzoate, isopropyl myristate, and 2-phenylethyl
      ester benzoic acid. The relative attractiveness of various doses of the main
      floral volatile compound phenylacetaldehyde (i.e., 10, 100, 200, and 400 mg) was
      tested for insect attraction. Both the total catch and the biodiversity of insect
      species trapped increased as the loading of phenylacetaldehyde increased.
      Volatiles were chosen from the odors from the flowers of Canada thistle and
      formulated and tested in the field. An 11-component blend was the most attractive
      of several floral blends tested. These findings indicate that chemical components
      of flower odors of Canada thistle can serve as a generic insect attractant for
      monitoring of invasive pest species.

PMID- 18613572
TI  - Behavior of bird cherry-oat aphid and green peach aphid in relation to potato
      virus Y transmission.
AB  - Potato virus Y is transmitted to potato in a nonpersistent manner by many aphid
      species, some of which do not colonize this crop. The behavior of bird cherry-oat
      aphid, Rhopalosiphum padi (L.) on potato, Solanum tuberosum L., a plant species
      that is not colonized by this aphid, was described and compared with that of the
      potato-colonizing green peach aphid, Myzuspersicae (Sulzer). A higher proportion
      of winged morph of R. padi than M. persicae left the plant, but aphids that
      stayed in contact with the plant took the same mean time to initiate the first
      probe and it lasted the same mean time compared with M. persicae. Electronic
      penetration graph technique was used to study the probing behavior of the aphids
      during Potato virus Y (family Potyviridae, genus Potyvirus, PVY) transmission
      tests. Transmission rate decreased from 29 to 8% when the acquisition time
      increased from 5 min of continuous probing to 1 h with M. persicae, but it
      remained low (2 and 1%) with R. padi. Most of the difference in transmission rate
      between acquisition time with M. persicae and between aphid species was related
      to the change in the time and behavior taking place between the last cell
      puncture of the acquisition phase to the first cell puncture of the inoculation
      phase. Results presented here clearly demonstrated the importance of host plant
      selection and probing behavior in the transmission of nonpersistent plant
      viruses. They also stress the need to consider the behavior of the aphid in the
      design of laboratory tests of virus vector efficacy.

PMID- 18613573
TI  - Thermal responses of oriental fruit fly (Diptera: Tephritidae) late third
      instars: mortality, puparial morphology, and adult emergence.
AB  - Responses of late third instars of the oriental fruit fly, Bactrocera dorsalis
      (Hendel) (Diptera: Tephritidae), to high temperatures (43, 46, and 48 degrees C)
      were investigated. The different heat exposures not only affected the timing of
      death but also induced different quantities of malformed puparia and changed the
      average eclosion time. A majority of larvae died immediately (as larvae) after 30
      min at 46 degrees C and > or =15 min at 48 degrees C, whereas most individuals
      died as pupae after 10-25 min of 46 degrees C, 5-10 min of 48 degrees C, and 40
      60 min of 43 degrees C treatments. Lethal times estimated by immediate mortality
      were longer than those estimated by delayed mortality at the same high
      temperature. Surviving larvae formed four types of puparial morphology (normal,
      bottlenose, larviform, and peanut form). The percentage of normal puparia showed
      a negative correlation with exposure time at all test temperatures. The number of
      bottlenose was more than the larviform and the peanut at 46 degrees C for < or
      =20 min and at 48 degrees C for < or =10 min, respectively, whereas the number of
      larviform was more than the bottlenose and the peanut at 46 degrees C and 48
      degrees C for longer exposure times. The average eclosion time increased at
      first, then decreased as the exposure time prolonged, and the longest average
      eclosion time occurred in the 40-min exposure at 43 degrees C, 15-min exposure at
      46 degrees C, and 10-min exposure at 48 degrees C.

PMID- 18613574
TI  - Using haplotypes to monitor the migration of fall armyworm (Lepidoptera:
      Noctuidae) corn-strain populations from Texas and Florida.
AB  - Fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae),
      infestations in most of North America north of Mexico arise from annual
      migrations of populations that overwinter in southern Texas and Florida. A
      comparison of the cytochrome oxidase I haplotype profiles within the fall
      armyworm corn-strain, the subgroup that preferentially infests corn (Zea mays L.)
      and sorghum (Sorghum vulgare Pers.), identified significant differences in the
      proportions of certain haplotypes between the Texas and Florida populations.
      These proportional differences were preserved as the populations migrated,
      providing a molecular metric by which the source of a migrant population could be
      identified. The migratory pattern derived from this method for several
      southeastern states was shown to be consistent with predictions based on analysis
      of historical agricultural and fall armyworm infestation data. These results
      demonstrate the utility of haplotype proportions to monitor fall armyworm
      migration, and they also introduce a potential method to predict the severity of
      cotton crop infestations in the short term.

PMID- 18613575
TI  - Olive fruit fly (Diptera: Tephritidae) ovipositional preference and larval
      performance in several commercially important olive varieties in California.
AB  - The olive fruit fly, Bactrocera oleae (Gmelin) (Diptera: Tephritidae),is an
      invasive pest of olives (Olea spp.) in the United States. The objectives of this
      study were to determine whether B. oleae exhibits ovipositional preference under
      California field conditions similar to that demonstrated in European populations
      and whether the resulting larvae fare better in preferred varieties. Female B.
      oleae exhibited strong ovipositional preference for certain varieties of the
      domesticated olive, Olea europaea L, and the resulting larvae performed better by
      some measures in preferred varieties than in lesser preferred varieties.
      Ovipositional preference was observed in the field from 2003 to 2005, and
      laboratory assays were conducted to evaluate larval performance in 2005 and 2006.
      Among the olive varieties tested, Sevillano, Manzanillo, and Mission olives were
      the most heavily infested during three consecutive years. The larval performance
      measurements used were pupal yield, pupal weight, larval developmental time, and
      pupal emergence time. Ovipositional preference and pupal yield do not seem
      associated. There were significant differences in pupal emergence time, but these
      also measures did not reflect ovipositional preference. Two measures on
      performance did seem related to ovipositional preference; there were significant
      effects of variety on pupal weight and larval developmental time. Pupae
      developing in Manzanillo and Sevillano olives were heavier than those developing
      in less preferred varieties, and larval developmental time was significantly
      shorter in Sevillano olives relative to the other varieties. Oviposition
      preference and enhanced larval performance has implications for the pest status
      of this invasive insect in California.

PMID- 18613576
TI  - Evaluation of SPLAT with spinosad and methyl eugenol or cue-lure for "attract-and
      kill" of oriental and melon fruit flies (Diptera: Tephritidae) in Hawaii.
AB  - Specialized Pheromone and Lure Application Technology (SPLAT) methyl eugenol (ME)
      and cue-lure (C-L) "attract-and-kill" sprayable formulations containing spinosad
      were compared with other formulations under Hawaiian weather conditions against
      oriental fruit fly, Bactrocera dorsalis (Hendel), and melon fly, Bactrocera
      cucurbitae (Coquillett) (Diptera: Tephritidae), respectively. Field tests were
      conducted with three different dispensers (Min-U-Gel, Acti-Gel, and SPLAT) and
      two different insecticides (naled and spinosad). SPLAT ME with spinosad was equal
      in performance to the standard Min-U-Gel ME with naled formulation up to 12 wk.
      SPLAT C-L with spinosad was equal in performance to the standard Min-U-Gel C-L
      with naled formulation during weeks 7 to12, but not during weeks 1-6. In
      subsequent comparative trials, SPLAT ME + spinosad compared favorably with the
      current standard of Min-U-Gel ME + naled for up to 6 wk, and it was superior from
      weeks 7 to 12 in two separate tests conducted in a papaya (Carica papaya L.)
      orchard and a guava (Psidium guajava L.) orchard, respectively. In outdoor paired
      weathering tests (fresh versus weathered), C-L dispensers (SPLAT + spinosad,
      SPLAT + naled, and Min-U-Gel + naled) were effective up to 70 d. Weathered ME
      dispensers with SPLAT + spinosad compared favorably with SPLAT + naled and Min-U
      Gel + naled, and they were equal to fresh dispensers for 21-28 d, depending on
      location. Our current studies indicate that SPLAT ME and SPLAT C-L sprayable
      attract-and-kill dispensers containing spinosad are a promising substitute for
      current liquid organophosphate insecticide formulations used for areawide
      suppression of B. dorsalis and B. cucurbitae in Hawaii.

PMID- 18613577
TI  - A new pheromone race of Acrobasis nuxvorella (Lepidoptera: Pyralidae).
AB  - The sex pheromone of the monophagous Acrobasis nuxvorella Neunzig (Lepidoptera:
      Pyralidae) was reported as (9E,11Z)-hexadecadienal (9E,11Z-16:Ald) (Biorg. Med.
      Chem. 4: 331-339, 1996), and it has since been an effective integrated pest
      management (IPM) tool for monitoring this pest in the United States, but not in
      Mexico. Field and laboratory studies were conducted to confirm that the species
      in Mexico was indeed A. nuxvorella and to investigate the pheromone chemistry of
      the Mexican populations of this species. Initial field trials testing compounds
      structurally related to the known pheromone component, and blends thereof,
      indicated that a 100 microg:100 microg blend of (9E,11Z)-hexadecadien-1-yl
      acetate (9E,11Z-16:Ac):9E,11Z-16:Ald in rubber septa was effective in attracting
      male moths in Mexico. Coupled gas chromatography-electroantennogram analyses
      confirmed the presence of these compounds in extracts of pheromone glands of
      females, and antennae of male moths also responded to the alcohol analog (9E,11Z)
      hexadecadien-1-ol (9E,11Z-16:OH). Subsequent field trials of various blends of
      these three compounds in Mexico showed that 1) both the acetate and aldehyde
      components were required for optimal attraction of male moths of the Mexican
      populations, and 2) addition of the alcohol suppressed attraction of males in a
      dose-dependent manner. Tests with the 1:1 9E,11Z-16:Ac:9E,11Z-16:Ald blend at
      various sites in the United States showed that this blend attracted some moths,
      but that moths attracted to 9E,11Z-16:Ald alone were predominant in the
      population. Furthermore, in preliminary studies the latter seemed not to respond
      to the blend. These findings indicate that there are two pheromone types of the
      pecan nut casebearer, and they have major implications for the direct use of
      these pheromones in pecan IPM.

PMID- 18613578
TI  - Biological and immune response of Galleria mellonella (Lepidoptera: Pyralidae) to
      sodium tetraborate.
AB  - Inorganic insecticides are commonly used in urban pest management because of
      their low mammalian toxicity. We tested the effects of sodium tetraborate (ST) on
      life parameters of greater wax moth, Galleria mellonella (L.) (Lepidoptera:
      Pyralidae), to determine its sublethal toxicity on the insect. Survival,
      development, adult longevity, and fecundity of the wax moth were investigated by
      rearing larvae on artificial diets containing ST at concentrations of 0.005, 0.1,
      0.2, or 0.3%. Larvae reared on medium at the highest concentration of ST (0.3%)
      had significantly decreased survival to the seventh instar and prolonged time
      required to reach the seventh instar. This concentration reduced pupa and adult
      yields to 12.5%, and it also prolonged development by 5 d. ST did not
      significantly influence adult longevity. Dietary ST led to significant decreases
      in fecundity and egg viability. Oviposition of survivors at the highest ST
      concentration (0.3%) was completely inhibited. Lysozyme content was decreased in
      larval hemolymph and fat body at high dietary ST concentrations. Fat body
      lysozyme content was significantly increased two-fold for larvae reared on diet
      at the lowest concentration of ST (0.005%). However, the highest concentration
      (0.3%) dramatically decreased fat body lysozyme content from 0.12 +/- 0.013 to
      0.006 +/- 0.003 mg/ml in seventh instars. We infer that sublethal levels of
      dietary ST substantially influence life history parameters and immunocompetence
      in G. mellonella.

PMID- 18613579
TI  - Lethal and sublethal effects of imidacloprid on Osmia lignaria and clothianidin
      on Megachile rotundata (Hymenoptera: Megachilidae).
AB  - We examined lethal and sublethal effects of imidacloprid on Osmia lignaria
      (Cresson) and clothianidin on Megachile rotundata (F.) (Hymenoptera:
      Megachilidae). We also made progress toward developing reliable methodology for
      testing pesticides on wild bees for use in pesticide registration by using field
      and laboratory experiments. Bee larvae were exposed to control, low (3 or 6 ppb),
      intermediate (30 ppb), or high (300 ppb) doses of either imidacloprid or
      clothianidin in pollen. Field experiments on both bee species involved injecting
      the pollen provisions with the corresponding pesticide. Only O. lignaria was used
      for the laboratory experiments, which entailed both injecting the bee's own
      pollen provisions and replacing the pollen provision with a preblended pollen
      mixture containing imidacloprid. Larval development, emergence, weight, and
      mortality were monitored and analyzed. There were no lethal effects found for
      either imidacloprid or clothianidin on O. lignaria and M. rotundata. Minor
      sublethal effects were detected on larval development for O. lignaria, with
      greater developmental time at the intermediate (30 ppb) and high doses (300 ppb)
      of imidacloprid. No similar sublethal effects were found with clothianidin on M.
      rotundata. We were successful in creating methodology for pesticide testing on O.
      lignaria and M. rotundata; however, these methods can be improved upon to create
      a more robust test. We also identified several parameters and developmental
      stages for observing sublethal effects. The detection of sublethal effects
      demonstrates the importance of testing new pesticides on wild pollinators before
      registration.

PMID- 18613580
TI  - Examining Cuphea as a potential host for western corn rootworm (Coleoptera:
      Chrysomelidae): larval development.
AB  - In previous crop rotation research, adult emergence traps placed in plots planted
      to Cuphea PSR-23 (a selected cross of Cuphea viscosissma Jacq. and Cuphea
      lanceolata Ait.) caught high numbers of adult western corn rootworms, Diabrotica
      virgifera virgifera LeConte (Coleoptera: Chrysomelidae), suggesting that larvae
      may have completed development on this broadleaf plant. Because of this
      observation, a series of greenhouse and field experiments were conducted to test
      the hypothesis that Cuphea could serve as a host for larval development.
      Greenhouse-grown plants infested with neonates of a colonized nondiapausing
      strain of the beetle showed no survival of larvae on Cuphea, although larvae did
      survive on the positive control (corn, Zea mays L.) and negative control
      [sorghum, Sorghum bicolor (L.) Moench] plants. Soil samples collected 20 June, 7
      July, and 29 July 2005 from field plots planted to Cuphea did not contain
      rootworm larvae compared with means of 1.28, 0.22, and 0.00 rootworms kg(-1)
      soil, respectively, for samples collected from plots planted to corn. Emergence
      traps captured a peak of eight beetles trap(-1) day(-1) from corn plots on 8 July
      compared with a peak of 0.5 beetle trap(-1) day(-1) on 4 August from Cuphea
      plots. Even though a few adult beetles were again captured in the emergence traps
      placed in the Cuphea plots, it is not thought to be the result of successful
      larval development on Cuphea roots. All the direct evidence reported here
      supports the conventional belief that rootworm larvae do not survive on broadleaf
      plants, including Cuphea.

PMID- 18613581
TI  - Is preventative, concurrent management of the soybean aphid (Hemiptera:
      Aphididae) and bean leaf beetle (Coleoptera: Chrysomelidae) possible?
AB  - In Iowa, the management of insect pests in soybean, Glycine max (L.) Merr., has
      been complicated by the arrival of the invasive species soybean aphid, Aphis
      glycines Matsumura (Hemiptera: Aphididae), and occasional outbreaks of bean leaf
      beetle, Cerotoma trifurcata (Forster) (Coleoptera: Chrysomelidae), populations
      leading to economic losses. Several insecticide programs designed to reduce
      abundance of the overwintered and first generation C. trifurcata and the
      incidence of bean pod mottle virus were evaluated over 3 yr (2004-2006) for their
      impacts on A. glycines populations, at three locations in Iowa (Floyd, Lucas, and
      Story counties). There was no significant overlap of either overwintered (early
      May) or the first (early July) generations of C. trifurcata with A. glycines,
      because aphids were first detected in June and they did not reach economically
      damaging levels until August, if at all. During this study, insecticides
      targeting the overwintered population or the first generation of C. trifurcata
      provided a limited impact on A. glycines populations compared with untreated
      controls, and they did not prevent economic populations from occurring.
      Furthermore, the highest populations of A. glycines were frequently observed when
      a low rate of lambda-cyhalothrin (178 ml/ha) was applied targeting the
      overwintered population of C. trifurcata. Soybean yields were not protected by
      any of the insecticide treatments. Our results indicate that the use of either
      early season foliar or seed-applied insecticides for C. trifurcata management is
      of limited value for A. glycines management.

PMID- 18613582
TI  - Impact of planting dates and insecticide strategies for managing crucifer flea
      beetles (Coleoptera: Chrysomelidae) in spring-planted canola.
AB  - Integration of cultural practices, such as planting date with insecticide-based
      strategies, was investigated to determine best management strategy for flea
      beetles (Phyllotreta spp.) (Coleoptera: Chrysomelidae) in canola (Brassica napus
      L.). We studied the effect of two spring planting dates of B. napus and different
      insecticide-based management strategies on the feeding injury caused by
      fleabeetles in North Dakota during 2002-2003. Adult beetle peak emergence usually
      coincided with the emergence of the early planted canola, and this resulted in
      greater feeding injury in the early planted canola than later planted canola. Use
      of late-planted canola may have limited potential for cultural control of flea
      beetle, because late-planted canola is at risk for yield loss due to heat stress
      during flowering. Flea beetle injury ratings declined when 1) the high rate of
      insecticide seed treatment plus a foliar insecticide applied 21 d after planting
      was used, 2) the high rate of insecticide seed treatment only was used, or 3) two
      foliar insecticide sprays were applied. These insecticide strategies provided
      better protection than the low rates of insecticide seed treatments or a single
      foliar spray, especially in areas with moderate-to-high flea beetle populations.
      The foliar spray on top of the seed treatment controlled later-emerging flea
      beetles as the seed treatment residual was diminishing and the crop became
      vulnerable to feeding injury. The best insecticide strategy for management of
      flea beetle was the high rate of insecticide seed treatment plus a foliar
      insecticide applied at 21 d after planting, regardless of planting date.

PMID- 18613583
TI  - Suppression of Ennomos subsignaria (Lepidoptera: Geometridae) on Acer
      pseudoplatanus (Aceraceae) in an urban forest with bole-implanted acephate.
AB  - Trees in an urban forest are highly valued because they have esthetic appeal,
      provide shade, and improve air quality. During the past 5 yr (2002-2006) in St.
      John's, Newfoundland and Labrador, Canada, the elm spanworm, Ennomos subsignaria
      (Hubner) (Lepidoptera: Geometridae), has reached outbreak densities. Each year,
      hundreds of trees have been completely defoliated, and many more trees have been
      partially defoliated. Adding to this problem, the larvae, their silk strands, and
      their frass are a considerable nuisance to property owners in areas of high
      larval densities. In this study, we evaluated the efficacy of three doses of bole
      implanted acephate (AceCap 97) for reducing densities and associated defoliation
      of E. subsignaria on sycamore maple, Acer pseudoplatanus L. (Aceraceae). During
      the treatment year (2005), all three doses significantly reduced E. subsignaria
      larval and pupal density; full or two-thirds doses significantly reduced
      defoliation compared with control trees. During the posttreatment year (2006),
      bole-implanted acephate did not affect E. subsignaria egg mass density, survival
      (= adult emergence), or defoliation. Bole-implanted acephate is an effective and
      practical way of suppressing E. subsignaria densities and herbivory in an urban
      forest where the protection of high-value trees and the reduction of
      environmental contamination are of utmost importance.

PMID- 18613584
TI  - Suitability of pines and other conifers as hosts for the invasive Mediterranean
      pine engraver (Coleoptera: Scolytidae) in North America.
AB  - The invasive Mediterranean pine engraver, Orthotomicus erosus (Wollaston)
      (Coleoptera: Scolytidae), was detected in North America in 2004, and it is
      currently distributed in the southern Central Valley of California. It originates
      from the Mediterranean region, the Middle East, and Asia, and it reproduces on
      pines (Pinus spp.). To identify potentially vulnerable native and adventive hosts
      in North America, no-choice host range tests were conducted in the laboratory on
      22 conifer species. The beetle reproduced on four pines from its native Eurasian
      range--Aleppo, Canary Island, Italian stone, and Scots pines; 11 native North
      American pines--eastern white, grey, jack, Jeffrey, loblolly, Monterey,
      ponderosa, red, Sierra lodgepole, singleleaf pinyon, and sugar pines; and four
      native nonpines--Douglas-fir, black and white spruce, and tamarack. Among
      nonpines, fewer progeny developed and they were of smaller size on Douglas-fir
      and tamarack, but sex ratios of progeny were nearly 1:1 on all hosts. Last,
      beetles did not develop on white fir, incense cedar, and coast redwood. With
      loblolly pine, the first new adults emerged 42 d after parental females were
      introduced into host logs at temperatures of 20-33 degrees C and 523.5 or 334.7
      accumulated degree-days based on lower development thresholds of 13.6 or 18
      degrees C, respectively.

PMID- 18613585
TI  - Detection of Anoplophora glabripennis (Coleoptera: Cerambycidae) larvae in
      different host trees and tissues by automated analyses of sound-impulse frequency
      and temporal patterns.
AB  - Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae), an invasive
      pest quarantined in the United States, is difficult to detect because the larvae
      feed unseen inside trees. Acoustic technology has potential for reducing costs
      and hazards of tree inspection, but development of practical methods for acoustic
      detection requires the solution of technical problems involving transmission of
      resonant frequencies in wood and high background noise levels in the urban
      environments where most infestations have occurred. A study was conducted to
      characterize sounds from larvae of different ages in cambium, sapwood, and
      heartwood of bolts from three host tree species. Larval sounds in all of the
      tested trees and tissues consisted primarily of trains of brief, 3-10-ms
      impulses. There were no major differences in the spectral or temporal pattern
      characteristics of signals produced by larvae of different ages in each tissue,
      but larval sounds in sapwood often had fewer spectral peaks than sounds in
      cambium and heartwood. A large fraction, but not all background sounds could be
      discriminated from larval sounds by automated spectral analyses. In 3-min
      recordings from infested bolts, trains containing impulses in patterns called
      bursts occurred frequently, featuring 7-49 impulses separated by small intervals.
      Bursts were rarely detected in uninfested bolts. The occurrence of bursts was
      found to predict infestations more accurately than previously used automated
      spectral analyses alone. Bursts and other features of sounds that are
      identifiable by automated techniques may ultimately lead to improved pest
      detection applications and new insight into pest behavior.

PMID- 18613586
TI  - Evaluation of cultural practices for potential to control strawberry sap beetle
      (Coleoptera: Nitidulidae).
AB  - Strawberry sap beetle, Stelidota geminata (Say) (Coleoptera: Nitidulidae), adults
      and larvae feed on and contaminate marketable strawberry (Fragaria L.) fruit. The
      beetle is a serious pest in the northeastern United States, with growers in
      multiple states reporting closing fields for picking prematurely due to fruit
      damage. Three options were evaluated for potential to reduce strawberry sap
      beetle populations. First, the influence of plant structure on accessibility of
      fruit in different strawberry cultivars to strawberry sap beetle was assessed by
      modifying plant structure and exposing caged plants to strawberry sap beetle
      adults. Severity of damage to berries staked up off the ground was similar to
      damage to those fruit contacting the soil, showing that adults will damage fruit
      held off the ground. Second, baited traps were placed at three distances into
      strawberry fields to determine whether overwintered beetles enter strawberry
      fields gradually. Adult beetles were first caught in the strawberries
      approximately equal to 19 d after occurring in traps placed along edges of
      adjacent wooded areas. The beetles arrived during the same sampling interval in
      traps at all distances into the fields, indicating that a border spray is
      unlikely to adequately control strawberry sap beetle. Third, the number of
      strawberry sap beetle emerging from strawberry for 5 wk after tilling and
      narrowing of plant rows was compared in plots renovated immediately at the end of
      harvest and in plots where renovation was delayed by 1 wk. In the 2-yr study,
      year and not treatment was the primary factor affecting the total number of
      emerging strawberry sap beetle. Overall, limited potential exists to reduce
      strawberry sap beetle populations by choosing cultivars with a particular plant
      structure, applying insecticide as a border spray, or modifying time of field
      renovation.

PMID- 18613587
TI  - Host plant choice experiments of Colorado potato beetle (Coleoptera:
      Chrysomelidae) in Virginia.
AB  - Field and laboratory-choice experiments were conducted to understand aspects of
      host plant orientation by the Colorado potato beetle, Leptinotarsa decemlineata
      Say (Coleoptera: Chrysomelidae), in Virginia. In laboratory bioassays, L.
      decemlineata oriented to volatiles emitted by potato, Solanum tuberosum L.,
      foliage over both tomato, Lycopersicon esculentum L., and eggplant, Solanum
      melongena L., foliage, and eggplant over tomato foliage, all of which had been
      mechanically damaged. Field choice tests revealed more L. decemlineata adults,
      larvae, and egg masses on eggplant than on tomato. In other experiments, counts
      of live L. decemlineata on untreated paired plants and counts of dead beetles on
      imidacloprid-treated plants did not differ between potato and eggplant. L.
      decemlineata was significantly attracted to eggplant over both tomato and pepper.
      To determine whether feeding adults affected orientation to host plants, an
      imidacloprid-treated eggplant or potato plant was paired with an untreated
      eggplant or potato plant covered in a mesh bag containing two adult male beetles.
      Significantly more adults were attracted to eggplant with feeding male beetles
      paired with another eggplant than any other treatment combination. These results
      indicate that the presence of male L. decemlineata on plants affects host plant
      orientation and suggests that the male-produced aggregation pheromone may be
      involved.

PMID- 18613588
TI  - Survival and development of immature stages of the Mediterranean fruit fly
      (Diptera: Tephritidae) in citrus fruit.
AB  - We studied, under laboratory conditions, the performance of the Mediterranean
      fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), immature stages
      in intact whole fruit of three sweet orange varieties, lemon, and bitter oranges.
      Both citrus variety and fruit part (flavedo, albedo, and pulp) had strong effects
      on larval performance, smaller effects on pupae, and no effects on eggs. Fruit
      peel was the most critical parameter for larval development and survival,
      drastically affecting larval survival (inducing very high mortality rates). Among
      fruit regions, survival of larvae placed in flavedo was zero for all varieties
      tested except for bitter orange (22.5% survival), whereas survival in albedo was
      very low (9.8-17.4%) for all varieties except for bitter orange (76%). Survival
      of pupae obtained from larvae placed in the above-mentioned fruit regions was
      high for all varieties tested (81.1-90.7%). Fruit pulp of all citrus fruit tested
      was favorable for larval development. The highest survival was observed on bitter
      oranges, but the shortest developmental times and heaviest pupae were obtained
      from orange cultivars. Pulp chemical properties, such as soluble solid contents,
      acidity, and pH had rather small effects on larval and pupal survival and
      developmental time (except for juice pH on larvae developmental duration), but
      they had significant effects on pupal weight.

PMID- 18613589
TI  - Phagostimulatory sugars enhance uptake and horizontal transfer of hexaflumuron in
      the western subterranean termite (Isoptera: Rhinotermitidae).
AB  - Western subterranean termite, Reticulitermes hesperus Banks (Isoptera:
      Rhinotermitidae), workers fed more on paper disks treated with the carbohydrates
      xylose, ribose, and fructose than on untreated disks. This feeding behavior of
      termites for certain carbohydrates was used to demonstrate an increase in the
      uptake and transfer of the insect growth regulator hexaflumuron among termites.
      The addition of 3% xylose to paper disks significantly increased the uptake of
      [14C]hexaflumuron and its subsequent transfer to other termites. Similarly, there
      was a significant increase in mortality of termites fed on paper disks treated
      with [14C]hexaflumuron (0.1 and 0.5%) in combination with 3% xylose for similar
      time periods compared with termites feeding on [14C]hexaflumuron (0.1 and 0.5%)
      alone. Overall percentage of mortality of termites feeding on [14C]hexaflumuron
      in combination with 3% xylose during the duration of the study (25-30 d) was
      approximately equal to 70%.

PMID- 18613590
TI  - Feeding preference of Coptotermes formosanus (Isoptera: Rhinotermitidae) for
      gamma-irradiated wood impregnated with benzoylphenylurea compounds under
      laboratory conditions.
AB  - The feeding preference of Coptotermes formosanus Shiraki (Isoptera:
      Rhinotermitidae) for 200-kGy gamma-irradiated Cryptomeria japonica D. Don
      (Japanese cedar) sapwood impregnated with benzoylphenylurea compounds such as
      hexaflumuron and noviflumuron was examined by three laboratory tests. Although
      termites were not deterred from feeding on gamma-irradiated wood samples that had
      been impregnated with hexaflumuron or noviflumuron, termite mortality was
      significantly higher compared with solvent controls in the no-choice test. All
      live termites were transferred to paper disks immediately after the no-choice
      test to investigate changes in mortality with time, and this test also confirmed
      the effects of hexaflumuron and noviflumuron on worker termites, which showed a
      significant feeding preference for gamma-irradiated wood. Only the 1480 ppm
      noviflumuron-impregnated gamma-irradiated wood specimens showed significant
      differences in mortality in the two-choice test. These results suggest that gamma
      irradiated C. japonica wood, which is locally abundant in Japan, may have
      potential as a bait substrate for benzoylphenylurea compounds.

PMID- 18613591
TI  - Interaction between the subterranean termite Reticulitermes flavipes (Isoptera:
      Rhinotermitidae) and the entomopathogenic fungus Metarhizium anisopliae in
      foraging arenas.
AB  - The entomopathogenic fungus Metarhizium anisopliae (Metsch.) Sorokin was tested
      in the laboratory against field-collected groups of eastern subterranean termite,
      Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae), in foraging arenas
      to determine the potential effect of a "trap and treat" protocol (trapping a part
      of the population, treating it with a biological control agent and releasing it
      back into the original population). Individual termites were treated with a
      suspension of M. anisopliae conidia and released back into the arenas containing
      untreated termites. After 5 d, 90% of the treated termites died in the arena, but
      untreated termites did not exhibit a significant increase in mortality within 90
      d after release, indicating no transfer of viable M. anisopliae and no epizootic.
      Although M. anisopliae was isolated from the arenas after 90 d, the average
      number of fungal colony-forming units recovered was <0.1% of the conidia
      introduced.

PMID- 18613592
TI  - Horizontal transfer of bait in the German cockroach: indoxacarb causes secondary
      and tertiary mortality.
AB  - Horizontal transfer of indoxacarb in the German cockroach, Blattella germanica
      (L.), was examined under laboratory conditions. Results show that a single bait
      fed adult cockroach (i.e., the donor) transferred indoxacarb to numerous primary
      recipients (secondary mortality),which then became secondary donors. These
      recipients subsequently became donors to other cockroaches and caused significant
      mortality in other members of the aggregation, resulting in tertiary kill.
      Indoxacarb was effectively transferred among adult cockroaches and resulted in
      significant secondary mortality. When adult males served as donors and vectored
      the insecticide to adult males, the donor:recipient ratio affected the mortality
      of the recipients and the rate of secondary mortality increased with increasing
      the ratio of donors to recipients. Furthermore, secondary mortality in the
      untreated cockroaches was significantly affected by the freshness of excretions
      from the donors, the presence of alternative food, and the duration of contact
      between the donors and the recipients. Ingested indoxacarb was most effectively
      translocated when the recipients interacted with freshly symptomatic donors in
      the absence of alternative food. The transfer of indoxacarb continued beyond
      secondary mortality and resulted in significant tertiary mortality. Excretions
      from a single bait-fed adult killed 38/50 (76%) nymphs within 72 h. The dead
      nymphs then vectored indoxacarb to 20 adult males and killed 16/20 (81%)
      recipients within 72 h. Behavioral mechanisms involved in the horizontal transfer
      of indoxacarb may include: contact with excretions, necrophagy, emetophagy, and
      ingestion of other excretions that originate from the donors.

PMID- 18613593
TI  - Influence of temperature on rate of uptake and subsequent horizontal transfer of
      [14C]fipronil by eastern subterranean termites (Isoptera: Rhinotermitidae).
AB  - The effect of temperature on [14C]fipronil uptake and transfer from donor (D) to
      recipient (R) Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae)
      workers was evaluated. Test chambers used in the fipronil uptake study were
      constructed from petri dishes containing autoclaved soil treated with 1 ppm
      [14C]fipronil (1.14 microCi of total radioactivity per petri dish), distilled
      water, and R. flavipes workers. Test chambers were held in environmental growth
      chambers preset at 12, 17, 22, 27, and 32 degrees C. For the fipronil transfer
      study, donor termites stained with Nile blue-A were exposed to soil treated with
      1 ppm [14C]fipronil for 2 h. Donors were then combined with unexposed recipient
      termite workers at either 1D:5R, 1D:10R, or 1D:20R ratios. Test chambers
      consisted of a nest and feeding chamber connected by a piece of polyethylene tube
      and held in growth chambers at 12, 17, 22, 27, and 32 degrees C. Worker termites
      were sampled over time and the amount of [14C]fipronil present was measured by
      scintillation counting. Some degree of uptake and transfer occurred at all
      temperatures and ratios in this study. The highest level of uptake occurred by
      termites held at 22-32 degrees C, followed decreasingly by 17 and 12 degrees C.
      Maximum transfer of [14C]fipronil occurred at the higher ratios (1:5 > 1:10 >
      1:20) of donors to recipients. Data presented in this study suggest that
      temperature is one of the key factors affecting the rate of uptake and subsequent
      horizontal transfer of [14C]fipronil in subterranean termites.

PMID- 18613594
TI  - Isolations of Cry2Ab resistance in Australian populations of Helicoverpa armigera
      (Lepidoptera: Noctuidae) are allelic.
AB  - Alleles conferring resistance to Cry2Ab toxin occur at a frequency of 0.0033 in
      Australian populations of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae),
      and it is evident that detectable levels of resistance predated the introduction
      of transgenic cotton expressing this toxin. From 2002 until 2006, 10 such
      resistant alleles were scored. Here, we examine colonies established from five of
      the 10 isolates by using complementation tests to determine their genetic
      relationships. The results demonstrate that the resistance in each colony is due
      to alleles at the same locus and that for each allele the resistance is
      recessive. This latter finding is in conflict with the frequency of apparently
      resistant individuals occurring in the initial F2 tests that were used to
      identify alleles that confer resistance. These frequencies were variable (range
      6.7-35.6%, mean 16.2%), but they generally indicated a measure of dominance
      (i.e., were >6.25% expected for recessive resistance). We hypothesize that this
      conflict is the result of differences in the genetic background of the laboratory
      adapted resistant colonies and the initial field isolations.

PMID- 18613595
TI  - Dynamically optimal strategies for managing resistance to genetically modified
      crops.
AB  - This paper develops a dynamic model of the evolution of pest a population and
      pest resistance to characterize the socially optimal refuge strategy for managing
      a pest's resistance to genetically modified crops. Previous theoretical economic
      analyses of this problem focus on steady states; we also address refuge policies
      along the optimal path to the final equilibrium. To elaborate on our theoretical
      analysis of the resistance problem, we develop a simulation model calibrated to
      cotton (Gossypium spp.) production in China. Our results show the importance of
      fitness cost as a determinant of the qualitative nature of optimal refuge
      policies.

PMID- 18613596
TI  - Inheritance of resistance to pyriproxyfen in Bemisia tabaci (Hemiptera:
      Aleyrodidae) males and females (B biotype).
AB  - We evaluated effects of the insect growth regulator pyriproxyfen on Bemisia
      tabaci (Gennadius) (B biotype) (Hemiptera: Aleyrodidae) males and females in
      laboratory bioassays. Insects were treated with pyriproxyfen as either eggs or
      nymphs. In all tests, the LC50 for a laboratory-selected resistant strain was at
      least 620 times greater than for an unselected susceptible strain. When insects
      were treated as eggs, survival did not differ between males and females of either
      strain. When insects were treated as nymphs, survival did not differ between
      susceptible males and susceptible females, but resistant males had higher
      mortality than resistant females. The dominance of resistance decreased as
      pyriproxyfen concentration increased. Resistance was partially or completely
      dominant at the lowest concentration tested and completely recessive at the
      highest concentration tested. Hybrid female progeny from reciprocal crosses
      between the susceptible and resistant strains responded alike in bioassays; thus,
      maternal effects were not evident. Rapid evolution of resistance to pyriproxyfen
      could occur if individuals in field populations had resistance with traits
      similar to those of the laboratory-selected strain examined here.

PMID- 18613597
TI  - Resistance allele frequency to bt cotton in field populations of helicoverpa
      armigera (Lepidoptera: Noctuidae) in China.
AB  - Resistance evolution in target insects to Bacillus thurningiensis (Bt) cotton,
      Gossypium hirsutum L., is a main threat to Bt cotton technology. An increasing
      trend of population density of Helicoverpa armigera (Hubner) (Lepidoptera:
      Noctuidae) has been observed since 2001 in Qiuxian County (Hebei, China), where
      Bt cotton has been planted dominantly since 1998. This region was selected in
      2006 and 2007 for estimating frequency of gene alleles conferring resistance to
      Bt cotton by screening the F1 progeny from single-pair cross between field
      collected male and laboratory female of the Bt-resistant strain of H. armigera
      (F1 screen). F1 offspring from each single-pair line were screened for resistance
      alleles based on larval growth, development, and survival on Bt cotton leaves for
      5 d. Two-year results indicated that approximately equal to 20% of field
      collected males carried resistance alleles. The conservative estimate of the
      resistance allele frequency was 0.094 (95% CI, 0.044-0.145) for 2006 and 0.107
      (95% CI, 0.055-0.159) for 2007. This is the first report of resistance allele
      frequency increase to such a high level in the field in China. Long-term adoption
      of Bt sprays, dominant planting of single-toxin-producing Bt cotton, and lack of
      conventional cotton refuge system might accelerate the resistance evolution in
      the region.

PMID- 18613598
TI  - Anatomical and nutritional factors associated with susceptibility of elms (Ulmus
      spp.) to the elm leaf beetle (Coleoptera: Chrysomelidae).
AB  - A wide range of susceptibility exists across elm (Ulmus) species and hybrids to
      the elm leaf beetle, Pyrrhalta luteola (Muller) (Coleoptera: Chrysomelidae). We
      evaluated various elm species, hybrids, or cultivars (taxa) growing in an
      experimental plantation in the city of Holbrook, AZ, for leaf anatomical
      (toughness and trichome density) and nutritional (minerals and sugars) traits
      that may be associated with host resistance. Leaf toughness and percentage of
      defoliation (susceptibility) were not correlated. However, we found weak negative
      correlations between percentage of defoliation and density of trichomes on the
      leaf abaxial surface. Of the 11 leaf nutrients examined, concentrations of iron
      and phosphorus correlated inversely with percentage of defoliation. The remaining
      nine traits did not show any correlation with percentage of defoliation. We
      concluded that individual anatomical and nutritional traits of elm
      species/hybrids do not seem to create a strong barrier to elm leaf beetle
      defoliation. However, the results from a stepwise multiple regression analysis
      indicated that collectively, these traits may play an important role in
      determining susceptibility.

PMID- 18613599
TI  - Reproductive rates of Russian wheat aphid (Hemiptera: Aphididae) biotypes 1 and 2
      on a susceptible and a resistant wheat at three temperature regimes.
AB  - The reproductive rates of Russian wheat aphid, Diuraphis noxia (Kurdjumov)
      (Hemiptera: Aphididae), Biotype 1 (RWA 1) and Biotype 2 (RWA 2) were compared in
      the laboratory at three temperature regimes on a Russian wheat aphid resistant
      cultivar ('Prairie Red') and a susceptible cultivar ('TAM 107'). The objective of
      this study was to expose RWA 1 and RWA 2 to three temperature regimes and two
      levels of resistance to find whether there were reproductive differences that may
      occur within each biotype as well as differences in reproduction between
      biotypes. In addition, temperature effects of the Dn4 gene on biotype
      reproduction were noted. Differences in reproductive rates between the two
      biotypes seem to be driven by temperature. For both biotypes, longevity and
      reproductive rate parameters, except for intrinsic rate of increase, were lower
      at the 24-29 degree C temperature regime than the 13-18 degree C and 18-24 degree
      C temperature regimes. The intrinsic rate of increase was higher for both
      biotypes at the 18-24 degree C and 24-29 degree C temperature regimes than at the
      13-18 degree C temperature regime. Reproductive rates between biotypes were
      similar at the two higher temperature regimes, but the fecundity for RWA 1 was
      less than RWA 2 at the 13-18 degree C temperature. The change in fecundity rates
      between RWA 1 and RWA 2 at lower temperatures could have ecological and
      geographical implications for RWA 2.

PMID- 18613600
TI  - Variation in tolerance and resistance to the leafhopper Empoasca fabae
      (Hemiptera: Cicadellidae) among potato cultivars: implications for action
      thresholds.
AB  - The potato leafhopper, Empoasca fabae (Harris) (Hemiptera: Cicadellidae), is an
      emerging pest of potato and insecticide applications to control this insect have
      increased in recent years. Based on field observations of leafhopper-crop
      dynamics, however, currently recommended action thresholds seem to be overly
      conservative. As a result, we initiated two experiments designed to quantify the
      impact of leafhoppers on potato yield, and determine how the magnitude of this
      effect changes among cultivars. In experiment 1, leafhoppers were manipulated
      (control versus insecticide-treated plots) on 17 potato varieties. In experiment
      2, three cultivars (Superior, Atlantic, and Snowden) were planted representing
      early-, mid-, and late-season maturing lines, and six insecticide spray regimes
      were imposed (early-, late-, and full-season applications at high and low rates).
      In both experiments, leafhopper abundance, plant damage, and potato yield were
      measured. Overall, leafhoppers reduced yield in control plots by 15.7% relative
      to insecticide-treated plots. Leafhopper impact, however, varied among cultivars;
      a significant effect of leafhoppers on yield was detected in 6, 12, and 59% of
      cultivars tested in each of three trials. Of the 44 cases in which leafhoppers
      exceeded action thresholds, yield loss was only documented in 13 cases. Data from
      these experiments provide evidence that such variable effects ofleafhoppers on
      yield are explained by cultivar-specific resistance and tolerance traits. Our
      results suggest that potato growers can accept higher leafhopper densities than
      current thresholds recommend, particularly when cultivating resistant and/or
      tolerant varieties.

PMID- 18613601
TI  - Using banded sunflower moth (Lepidoptera: Tortricidae) egg density to estimate
      damage and economic distance in oilseed sunflower.
AB  - The banded sunflower moth, Cochylis hospes Walsingham (Lepidoptera: Tortricidae),
      is an important economic pest of sunflower in the Upper Great Plains of North
      America. Economic losses due to reductions in seed number, weight, and quality
      can be significant. Previously, the potential for economic losses were estimated
      by sampling for adult moths. However, sampling for moths can be difficult and
      inaccurate. An alternative is to sample for banded sunflower moth eggs, which can
      be accurately counted in the field by using a binocular 3.5 headband magnifier.
      The egg counts are used to calculate the economic injury level (EIL) (EIL =
      C/VWPK), where C is the cost of treatment per unit area, V is the crop market
      value per unit of weight, W is the slope of the regression between banded
      sunflower moth egg densities and weight loss per plant, P is a term for plant
      population per unit area, and K is the control treatment efficacy. Estimates of
      populations of banded sunflower moth eggs are taken from the center of 400-m
      spans along all field sides. From these samples and the calculated EIL, a map of
      the extent of the economically damaging banded sunflower moth population
      throughout the field is made using economic distance; ED = e ( ( (EIL/E)-1.458)/
      0.262). Economic distance estimates the distance an economic population extends
      into the field interior along a transect from the sampling site. By using egg
      samples to calculate the EIL and mapping the distribution of economic populations
      throughout a field, producers can then make more effective pest management
      decisions.

PMID- 18613602
TI  - Effect of temperature and commodity on insecticidal efficacy of spinosad dust
      against Sitophilus oryzae (Coleoptera: Curculionidae) and Rhyzopertha dominica
      (Coleoptera: Bostrychidae).
AB  - The insecticidal effect of spinosad dust, a formulation that contains 0.125%
      spinosad, was evaluated against adults of Sitophilus oryzae (L.) and Rhyzopertha
      dominica (F.) at three temperature levels (20, 25, and 30 degrees C) and four
      commodities (wheat, Triticum aestivum L.; barley, Hordeum vulgare L.; rice, Oryza
      sativa L.; and maize, Zea mays L.). For this purpose, quantities of the above
      mentioned grains were treated with spinosad at two dose rates (20 and 50 ppm of
      the formulation, corresponding to 0.025 and 0.06 ppm AI, respectively), and
      mortality of the exposed adults in the treated grains was measured after 7 and 14
      d, whereas progeny production was assessed 65 d later. Generally, for both
      species, mortality increased with dose, exposure interval, and temperature. For
      S. oryzae, adult survival and progeny production were lower on wheat than the
      other grains. After 14 d of exposure, mortality of S. oryzae adults on wheat
      treated with 50 ppm ranged between 61 and 98%, whereas in the other three
      commodities it did not exceed 42%. Mortality of R. dominica after 14 d on grains
      treated 50 ppm ranged between 91 and 100%. For this species, progeny production
      from exposed parental adults was low in all commodities regardless of
      temperature. Results indicate that spinosad dust can be used as an alternative to
      traditional grain protectants, but its effectiveness is highly determined by the
      target species, commodity, dose, and temperature.

PMID- 18613603
TI  - Life tables of Habrobracon hebetor (Hymenoptera: Braconidae) parasitizing
      Anagasta kuehniella and Plodia interpunctella (Lepidoptera: Pyralidae): effect of
      host density.
AB  - The reproductive performance of the parasitoid Habrobracon hebetor (Say)
      (Hymenoptera: Braconidae) against the moths Anagasta kuehniella Zeller and Plodia
      interpunctella (Hubner) (Lepidoptera: Pyralidae) was studied in the laboratory.
      The analysis was based on the comparison of parasitoid's life table parameters
      related to those of its hosts at various conditions of host density (daily supply
      of 1, 5, 15, and 30 full-grown host larvae). The estimated parameters were the
      intrinsic rate of natural increase (rm), the net reproductive rate (R0), the mean
      generation time (G), the finite capacity of increase (lambda), the gross
      reproductive rate (GRR), the doubling time (DT), the reproductive value (Vx), and
      the life expectancy (ex). The rm of H. hebetor proved to be significantly higher
      than those of its hosts at all host densities. When only one host per day was
      supplied, the wasp had the lowest reproductive potential, whereas it was
      maximized when 15 hosts per day were exposed. Maximum values of R0 and GRR were
      obtained at densities > or =15 host larvae per day. Any increase in host supply
      above this threshold did not cause significant changes in life table parameters.
      Variation of rm as a function of host density can be described by the linear
      regression. Sex ratio of wasp progeny (females/total) ranged from 0.36 to 0.42,
      irrespective of host density or species. Newly emerged adults recorded maximum ex
      and Vx. The results of this study can be used to improve mass rearing programs
      and inoculative release applications of H. hebetor against moth pests of stored
      products.

PMID- 18613604
TI  - Dynamic model for predicting survival of mature larvae of Tribolium confusum
      during facility heat treatments.
AB  - Structural heat treatment, a viable alternative to methyl bromide fumigation,
      involves raising the ambient temperature of food-processing facilities between 50
      and 60 degrees C by using gas, electric, or steam heaters, and holding these
      elevated temperatures for 24 h or longer to kill stored-product insects. A
      dynamic model was developed to predict survival of mature larvae, which is the
      most heat-tolerant stage of the confused flour beetle, Tribolium confusum
      (Jacquelin du Val), at elevated temperatures between 46 and 60 degrees C. The
      model is based on two nonlinear relationships: 1) logarithmic survival of T.
      confusum mature larvae as a function of time, and 2) logarithmic reduction in
      larval survival as a function of temperature. The dynamic model was validated
      with nine independent data sets collected during actual facility heat treatments
      conducted on two separate occasions at the Kansas State University pilot flour
      and feed mills. The rate of increase of temperature over time varied among the
      nine locations where mature larvae of T. confusum were exposed, and the
      approximate heating rates during the entire heat treatment ranged from 1.1 to
      13.2 degrees C/h. The absolute deviation in the predicted number of larvae
      surviving the heat treatment was within 3-7% of the actual observed data.
      Comparison of the absolute deviation in the time taken for equivalent larval
      survival showed that the model predictions were within 2-6% of the observed data.
      The dynamic model can be used to predict survival of mature larvae of T. confusum
      during heat treatments of food-processing facilities based on time-dependent
      temperature profiles obtained at any given location.

PMID- 18613605
TI  - Stored-product insects associated with eight feed mills in the midwestern United
      States.
AB  - Commercial food- and pheromone-baited pitfall traps and pheromone-baited sticky
      traps were used during 2003 to survey stored-product insect adults in eight
      participating feed mills in the midwestern United States. Across the eight feed
      mills, 27 species of beetles (Coleoptera) and three species of moths
      (Lepidoptera) were captured in commercial traps. The red flour beetle, Tribolium
      castaneum (Herbst), was the most abundant insect species captured inside the
      eight mills. The warehouse beetle, Trogoderma variabile (Ballion), was the most
      abundant insect species outside the mill and in the mill load-out area. The
      Indianmeal moth, Plodia interpunctella (Hubner), was the most abundant moth
      species inside the mill and in the mill receiving area. The Simpson's index of
      species diversity among mills ranged from 0.39 (low diversity) to 0.81 (high
      diversity). The types of species found among mills were different, as indicated
      by a Morisita's index of <0.7, for the majority of mills. The differences in the
      types and numbers of insect species captured inside, outside, in receiving, and
      in load-out areas could be related to differences in the types of animal feeds
      produced and the degree of sanitation and pest management practiced.

PMID- 18613606
TI  - Infestation and development of Sitophilus spp. in pouch-packaged spaghetti in
      Japan.
AB  - Infestation of pouch-packaged spaghetti by Sitophilus oryzae (L.) (Coleoptera:
      Curculionidae) was observed in Japan in May 2006. It was suggested that 30% of
      all shipped pasta products sustain damage to the packages heat-sealed before
      reaching retail stores. Hence, we investigated the mechanisms by which S. oryzae
      and Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) adults invade
      pasta packaged in polypropylene pouches. In the damaged packages, both species
      entered through the breaks in the seal and laid their eggs on the pasta. However,
      in the intact packages, the adults of both species bit around air vent holes in
      the film, but they did not make the holes big enough for entry into the pouch. We
      also compared each species' developmental periods from oviposition to emergence
      in pasta and brown rice (Oryza spp.). The average developmental period of both
      species at 25 degrees C was shorter in rice than in pasta. The number of
      individuals emerging from brown rice was significantly higher than that from
      pasta. Finally, we suggested a measure to prevent infestation by insect pests in
      pouch-packaged pasta products.

PMID- 18613607
TI  - Determination of mortality of different life stages of Tribolium castaneum
      (Coleoptera: Tenebrionidae) in stored barley using microwaves.
AB  - Barley, Hordeum vulgare L., one of the important crops in Canada, is used in
      malting, feed, and food industries. Disinfestation of barley using microwaves can
      be an alternative to chemical methods used to kill insects. A pilot-scale
      industrial microwave system operating at 2.45 MHz was used in this study to
      determine the mortality of life stages (egg, larva, pupa, and adult) of Tribolium
      castaneum (Herbst) (Coleoptera: Tenebrionidae). Barley samples of 50 g each at
      14, 16, and 18% moisture content (MC; wet basis) were infested with various life
      stages of T. castaneum and exposed to microwave energy at different power levels
      and exposure times, and the mortality of the insects was determined. The average
      temperature of the 14% MC sample exposed to 28 s at 0, 200, 300, 400, and 500 W
      were 27.4, 42.6, 53.7, 66.9, and 73.0 degrees C, respectively, and those exposed
      to 56 s at 0, 200, 300, and 400 W were 27.4, 57.3, 75.5, and 91.2 degrees C,
      respectively. A similar range of temperature was observed for 16 and 18% MC
      barley. Complete mortality of all life stages of T. castaneum can be achieved at
      a power level of 400 W and an exposure time of 56 s or at 500 W for 28 s. Among
      the life stages of T. castaneum, eggs were the most susceptible to microwave
      energy and adults were the least susceptible. There was no significant difference
      in the mortality of larvae and adults at 14, 16, and 18% MC, but the mortality
      was significantly different for eggs and pupae at different MCs. There was a
      significant increase in the mortality with an increase in power level or exposure
      time or both. Germination capacity of the seeds was decreased with an increase in
      power level or exposure time or both. Quality characteristics such as alpha
      amylase, diastatic power, soluble protein, viscosity, and density of the barley
      malt treated at 500 W for 28 s were same as the control sample, whereas the
      samples treated at 400 W for 56 s were significantly lower.

PMID- 18613608
TI  - Immediate and delayed mortality of Rhyzopertha dominica (Coleoptera:
      Bostrichidae) and Sitophilus oryzae (Coleoptera: Curculionidae) adults exposed to
      spinosad-treated commodities.
AB  - A series of tests was conducted to characterize differences in the mortality of
      the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae), and
      rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), exposed to three
      commodities treated with a liquid and dry spinosad formulation. In laboratory
      bioassays, adults of the two insect species were exposed to untreated wheat,
      Triticum aestivum L., corn, Zea mays L., and sorghum, Sorghum bicolor (L.)
      Moench., and to commodities treated with 1 mg (AI)/kg of liquid and dry spinosad
      formulations. Mortality was assessed from independent samples examined at
      specific time intervals to determine immediate mortality and after 24 h of
      recovery on untreated grain at 28 degrees C and 65% RH to determine delayed
      mortality. Comparison of the time required for 50% (LT50) and 95% (LT95)
      mortality indicated that R. dominica adults were consistently and significantly
      more susceptible (died quickly) than S. oryzae adults when exposed to spinosad
      treated commodities. In general, the toxicity of liquid and dry spinosad
      formulations was similar against R. dominica or S. oryzae. The toxicity of
      spinosad to each species varied slightly among the three commodities, and there
      were no consistent trends to suggest that spinosad was more effective on one
      commodity versus another. LT50 values based on immediate mortality for R.
      dominica on all commodities ranged from 0.45 to 0.74 d; corresponding values
      based on delayed mortality ranged from 0.04 to 0.23 d, suggesting delayed toxic
      action of spinosad in R. dominica. LT50 values based on immediate and delayed
      mortality for S. oryzae on all three commodities treated with the two spinosad
      formulations were essentially similar and ranged from 2.75 to 4.56 d. LT95 values
      for R. dominica based on immediate mortality on spinosad-treated commodities
      ranged from 1.75 to 3.36 d, and those based on delayed mortality ranged from 0.49
      to 1.88 d. There were no significant differences in LT95 values based on
      immediate and delayed mortality for S. oryzae on spinosad-treated commodities,
      and the LT95 values ranged from 7.62 to 18.87 d. The toxicity of spinosad was
      enhanced during a 24-h holding period after removal from spinosad-treated
      commodities only against R. dominica adults, and possible reasons for increased
      postexposure mortality of R. dominica adults after brief exposures to spinosad
      warrant further study.

PMID- 18613609
TI  - Chitin in the peritrophic membrane of Acarus siro (Acari: Acaridae) as a target
      for novel acaricides.
AB  - The peritrophic membrane in Acarus siro L. (Acari: Acaridae) is produced by
      distinct cells located in the ventriculus. In this study, the chitin inside the
      peritrophic membrane was detected using wheat germ-lectin conjugated with
      colloidal gold (10 nm). The chitin fibrils of the peritrophic membrane were a
      target for chitin effectors, including 1) chitinase, which hydrolyzes chitin
      fibers inside the peritrophic membrane; 2) calcofluor, which binds to chitin and
      destroys the peritrophic membrane mesh structure; and 3) diflubenzuron, which
      inhibits chitin synthesis. In addition, soybean trypsin protease inhibitor (STI)
      and cocktails of chitinase/calcofluor, diflubenzuron/calcofluor and chitinase/STI
      were tested. These compounds were supplemented in diets and an increase of
      population initiated from 50 individuals was observed after 21 d of cultivation.
      Final A. siro densities on experimental and control diets were compared. The
      chitin in the peritrophic membrane was determined to be a suitable target for
      novel acaricidal compounds for suppressing the population growth of A. siro. The
      most effective compounds were calcofluor and diflubenzuron, whereas the
      suppressive effects of chitinase and STI were low. The failure of chitinase could
      be due to its degradation by endogenous proteases. The combination of chitinase
      and STI suppressed A. siro population growth more effectively than when they were
      tested in oral admission separately. The combinations of calcofluor/chitinase or
      calcofluor/difluorbenzuron showed no additive effects on final A. siro density.
      The presence of chitin in peritrophic membrane provides a target for novel
      acaricidal compounds, which disrupt peritrophic membrane structure. The
      suitability of chitin effectors and their practical application in the management
      of stored product mites is discussed.

PMID- 18613610
TI  - Evaluation of different insecticides and fabric types for development of treated
      targets for stable fly (Diptera: Muscidae) control.
AB  - Stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), once only a pest of
      pastured cattle, has become a serious pest of range cattle in the United States.
      Because of the difficulties associated with stable fly management under range
      conditions, a pesticide-impregnated cloth target is being developed as a
      management tool. We conducted studies to determine the influence of weather,
      time, fabric type, insecticide type, and insecticide concentration on the
      mortality of stable flies from a susceptible laboratory colony exposed for 30 s
      to treated cloth targets. We found that 100% of the flies exposed to trigger
      (Trigger-Royal Box, 65% polyester and 35% cotton) fabric targets that were
      treated with 0.1% h-cyhalothrin or 0.1% zeta-cypermethrin and weathered outdoors
      in Gainesville, FL., for up to 3 mo, were dead within 20 min after a 30-s
      exposure. The results of this study support the concept that treated targets can
      be developed for integration into stable fly control programs.

PMID- 18613611
TI  - Trace elements removal from water using modified activated carbon.
AB  - This paper present the possible alternative options for the remove of trace
      elements from drinking water supplies in the trace. Arsenic and chromium are two
      of the most toxic pollutants, introduced into natural waters from a variety of
      sources and causing various adverse effects on living bodies. The performance of
      three filter bed methods was evaluated in the laboratory. Experiments were
      conducted to investigate the sorption of arsenic and chromium on carbon steel and
      removal of trace elements from drinking water with a household filtration
      process. The affinity of the arsenic and chromium species for Fe/Fe3C (iron/iron
      carbide) sites is the key factor controlling the removal of the elements. The
      method is based on the use of powdered block carbon, powder carbon steel and
      ceramic spheres in the ion-sorption columns as a cleaning process. The modified
      powdered block carbon is a satisfactory and economical sorbent for trace elements
      (arsenite and chromate) dissolved in water due to its low unit cost of about $23
      and compatibility with the traditional household filtration system.

PMID- 18613612
TI  - Commissioning of the gigantic anaerobic sludge digesters at the wastewater
      treatment plant of Athens.
AB  - The pre-commissioning strategy, the start-up procedure and the analytical data
      obtained during the commissioning period for the first of the four new anaerobic
      gigantic digesters, with active volume of 10,000 m3 each, are presented in this
      paper. The digester was initially filled up with water, and the temperature was
      raised to 36 +/- 1 degrees C. Then, a total amount of 1,860 m3 of digested
      primary sludge was transferred, in four equal daily batches, into the digester
      from neighbouring digesters, performing routine operation. Following this, the
      digester was gradually fed with fresh primary thickened sludge, up to the point
      that the retention time reached approximately 20 d. A number of significant
      operational parameters (pH, alkalinity, total and volatile solids concentration,
      volatile fatty acids concentration, biogas production rate and composition) were
      monitored several times per day, and the appropriate adjustments were performed
      in order to achieve stable operation. The time duration of the whole process was
      about two and a half months. Later on, the digester was supplied with a mixture
      of primary and biological sludge.

PMID- 18613613
TI  - Influence on permeability of the structural parameters of heterogeneous porous
      media.
AB  - Predicting the macroscopic properties of porous media used in treatment processes
      is a complex task regarding 3-D structures at micro-, meso- and macro-levels.
      Currently, information is scarce concerning the influence, at a microscopic level
      of the 3-D structure of fibrous media on the physical laws governing their
      macroscopic behaviour. Nevertheless, the relationship between macroscopic
      properties (pressure drop, treatment efficiency) and microstructure can be
      assessed thanks to suitable structure modelling theories. In this context, the
      present study proposes and compares different methods (mercury porosimetry and
      image analysis) for the structure characterization at a microscopic level of
      filtering fibrous media, such as nonwoven and woven fabrics. The results obtained
      show a porous structure gradient in the thickness of the nonwoven media studied
      in terms of porosity, pore size and tortuosity factor. Moreover, the influence on
      structural parameters of media compression, when submitted to friction forces
      exerted by flow during filtration tests, is established. A model for the
      determination of multi-level pore size distributions from mercury porosimetry
      data is proposed. The "equivalent pore" model is used to estimate the tortuosity
      factor. The influence of measured structural parameters on fibrous media
      permeability is studied in a classical model for flow through fibrous media.

PMID- 18613614
TI  - Kinetics of propionate conversion in anaerobic continuously stirred tank
      reactors.
AB  - The kinetic parameters of anaerobic propionate degradation by biomass from 7
      continuously stirred tank reactors differing in temperature, hydraulic retention
      time and substrate composition were investigated. In substrate-depletion
      experiments (batch) the maximum propionate degradation rate, Amax, and the half
      saturation constant, Km, were initially estimated by applying the integrated
      Michaelis-Menten equation. Amax was in the range from 22.8 to 29.1 micromol gVS(
      1) h(-1) while Km was in the range from 0.46-0.95 mM. In general, Amax gave a
      good reflection of the reactor performances. Secondly, the accuracy of the
      applied method was evaluated by use of radiotracer methodology. Amax was found to
      be 14-15% lower in the substrate-depletion experiment than in the radioisotope
      experiment due to endogenous propionate production. By including the endogenous
      propionate production, a 42-49% lower Km was estimated. The results demonstrate
      that the rate of endogenous substrate (propionate) production should be taken
      into account when estimating kinetic parameters in biomass from manure-based
      anaerobic reactors.

PMID- 18613615
TI  - Bacillus thuringiensis fermentation of wastewater and wastewater sludge--presence
      and characterization of chitinases.
AB  - This study investigated the presence of chitinases in Bacillus thuringiensis ssp
      kurstaki HD-1 (Bt) fermented broths of wastewater sludge (non-hydrolyzed and
      hydrolyzed); starch industry wastewater and soyameal. Chitinase activity was
      absent in soyameal and present in others. Chitinase demonstrated peaks at pH 4.0
      and temperatures 40 and 50 degrees C with higher activity between pH 4-5 and 10
      11. The chitinase band on SDS-PAGE was found to be between 36 and 45 kDa for non
      hydrolyzed (NH) and hydrolyzed sludge (TH) and starch industry wastewater. The
      chitinase profile during fermentation showed peaks at 15 and 30 h for non
      hydrolyzed and hydrolyzed sludge and 15 and 24 h for starch industry wastewater.
      Chitinase retained 96-99 % activity after two weeks incubation at room
      temperature and pH 4. Bioassays with supplementation of Bt chitinases showed 1.2
      fold increase in entomotoxicity of wastewater sludge and a small increase in
      starch industry wastewater. This study sheds light on production of Bt chitinases
      in alternative media which will have a long term effect on entomotoxicity of
      these formulations.

PMID- 18613616
TI  - Oil-removal enhancement in media with keratinous or chitinous wastes by
      hydrocarbon-degrading bacteria isolated from oil-polluted soils.
AB  - The aim of this work was to isolate oil-degrading bacteria that use chitin or
      keratin as carbon sources from oil contaminated soils; and additionally to study
      if oil removal by these bacteria is enhanced when a chitinous or a keratinous
      waste is added to the culture media. To isolate the above-mentioned bacteria, 12
      soil samples were collected close to an oil-well. Such soils showed unsuitable
      nutrients content, but their counts of heterotrophic bacteria ranged within 10(5)
      10(8) CFU g(-1) soil, of which 0.1-77% corresponded to oil hydrocarbon-degrading
      ones. By sampling on plates, 109 oil-degrading bacterial isolates were obtained.
      Their keratinase and chitinase activities were then screened by plate assays and
      spectrophotometric methods, resulting in 13 isolates that were used to integrate
      two mixed cultures, one keratinolytic and the other chitinolytic. These mixed
      cultures were grown in media with oil, or oil supplemented with chicken-feathers
      or shrimp wastes. The oil-hydrocarbon removal was measured by gas chromatography.
      Results showed that keratinolytic bacteria were better enzyme producers than the
      chitinolytic ones, and that oil removal in the presence of chicken-feathers was
      3.8 times greater than with shrimp wastes, and almost twice, in comparison with
      oil-only added cultures. Identification of microorganisms from the mixed cultures
      by 16S rDNA, indicated the presence of seven different bacterial genera;
      Stenotrophomonas, Pseudomonas, Brevibacillus, Bacillus, Micrococcus, Lysobacter
      and Nocardiodes. These findings suggest that the isolated microorganisms and the
      chicken-feather wastes could be applied to the cleaning of oil-contaminated
      environments, whether in soil or water.

PMID- 18613617
TI  - Sequential anaerobic, aerobic/anoxic treatment of simulated landfill leachate.
AB  - In this study COD, ammonia and nitrate were treated through methanogenesis,
      nitrification denitrification and anammox processes in anaerobic-aerobic and
      anaerobic/anoxic sequential in leachate samples produced from municipal solid
      waste in an anaerobic simulated landfilling bioreactor. The experiments were
      performed in an upflow anaerobic sludge blanket reactor (UASB), aerobic
      completely stirred tank reactor (CSTR) and upflow anaerobic/anoxic sludge blanket
      reactor (UA/A(N)SB). Hydraulic retention times in anaerobic, aerobic and
      anaerobic/anoxic stages were 1, 3.6 and 1 days, respectively, through 244 days of
      total operation period with 168 days of adaptation period of microorganisms to
      the reactors. The organic loading rates increased from 5.9 to 50 kg COD m(-3)
      day(-1). The total COD and TN removal efficiencies of the anaerobic-aerobic
      anoxic system were 96% and 99%, respectively, at an influent OLR as high as 50 kg
      COD m(-3) day(-1). The maximum methane percentage in the UASB reactor was 82%
      while the methane percentage was zero in UA/A(N)SB reactor for the aforementioned
      OLR at the end of steady-state conditions. NH4-N removal efficiency of the
      aerobic reactor was 90% while anaerobic ammonia oxidation was measured as 99% in
      the anoxic reactor. The denitrification efficiency was 99% in the same reactor.
      Total TN removal of the whole system was 99%.

PMID- 18613618
TI  - Fatty acid methyl ester (FAME) technology for monitoring biological foaming in
      activated sludge: full scale plant verification.
AB  - Fatty acid methyl ester (FAME) technology was evaluated as a monitoring tool for
      quantification of Gordonia amarae in activated sludge systems. The fatty acid,
      19:1 alcohol, which was identified as a unique fatty acid in G. amarae was not
      only confirmed to be present in foaming plant samples, but the quantity of the
      signature peak correlated closely with the degree of foaming. Foaming potential
      experiment provided a range of critical foaming levels that corresponded to G.
      amarae population. This range of critical Gordonia levels was correlated to the
      threshold signature FAME amount. Six full-scale wastewater treatment plants were
      selected based on a survey to participate in our full-scale study to evaluate the
      potential application of the FAME technique as the Gordonia monitoring tool.
      Greater amounts of signature FAME were extracted from the mixed liquor samples
      obtained from treatment plants experiencing Gordonia foaming problems. The
      amounts of signature FAME correlated well with the conventional filamentous
      counting technique. These results demonstrated that the relative abundance of the
      signature FAMEs can be used to quantitatively monitor the abundance of foam
      causing microorganism in activated sludge.

PMID- 18613619
TI  - [Annual distribution of bacterial indicators generated by the domestic wastes
      from the landfill of Etueffont (France)].
AB  - We assessed over 15 months the distribution of total coliforms concentrations of
      Escherichia coli, Enterococci, Pseudomonas aeruginosa, Salmonella and
      Staphylococcus aureus in three monitoring points in the Etueffont landfill
      (Belfort, France). We selected the piezometer (PZ30) which is located downstream
      from the dump and two leachate collectors from the old dump and the new casing.
      The results showed that the leachate was free from both Salmonella and
      Staphylococcus aureus. The absence of Salmonella was most likely due to the small
      occupation of the landfill environment by vertebrates, especially rodents, birds
      and reptiles, which are known to be principal vectors of Salmonella. S. aureu, is
      generally hosted on skins and mucus of animals. The mean densities of E. coli and
      Enterococcus in the leachates were low. In contrast, P. aeruginosa abundance was
      high and closely related to precipitations. Coliform bacteria concentrations in
      the leachate averaged UFC.100 CFU x ml(-1). In the contaminated groundwaters, the
      coliforms, E. coli and Enterococci were always present at concentrations 10 to
      100 fold higher than those reported from septic tank effluents. P. aeruginosa
      concentrations were low (mean: 11 CFU.100 ml(-1)) and inferior to those quoted in
      the leachate. This may be explained by the anoxic conditions which prevailed in
      the shistous aquifer. The absence of Salmonella in groundwaters may be due to its
      sensitivity to disinfectants and that of S. aureus linked to the fact that it is
      not a common host of the human intestine. Finally, our study clearly indicates
      the role played by E. coli and Enterococci as biomarkers of recent faecal
      contamination.

PMID- 18613620
TI  - Study of arsenic content in mine groundwater commonly used for human consumption
      in Utah.
AB  - Of the various sources of arsenic released in to the environment, the presence of
      arsenic in water probably poses the greatest threat to human health. Arsenic is
      released in to the environment through water by dissolution of minerals and ores.
      Natural release is slow, but in some areas the concentration of arsenic in
      groundwater (commonly referred to as Acid Mine Drainage (or AMD)) is accelerated
      by mining activity. In fact the presence of arsenic may last a long time even
      after the mining activity has ceased. Hence it is imperative to study the quality
      of water (especially for those areas in the vicinity of mines) used for different
      purposes to identify an appropriate remediation technique for effective pollution
      control. In this paper, contents of arsenic and other metals in the water were
      quantified from three different sources: (1) groundwater from the mining tunnel
      (Judge tunnel), (2) drinking water, and (3) water used in the hydrant-flushed
      distribution system (Park City) in Utah (USA). The results showed the content of
      arsenic from the mining tunnel, after chlorination, and in tap water were below
      10 microgl(-1). However, significant amounts of arsenic, lead, zinc, iron,
      manganese and antimony have been found in water samples taken from the
      distribution systems. In the consideration of the further use of mine groundwater
      for drinking purposes and the distribution system, Park City should regularly be
      maintained by a flushing program in the distribution system.

PMID- 18613621
TI  - Treatment of wastewater containing phenol using a tubular ceramic membrane
      bioreactor.
AB  - The performance of a membrane bioreactor (MBR) with a tubular ceramic membrane
      for phenol removal was evaluated under varying hydraulic retention times (HRT)
      and a fixed sludge residence time (SRT) of 30 days. The tubular ceramic membrane
      was operated with a mode of 15 minutes of filtration followed by 15 seconds of
      permeate backwashing at a flux of 250 l m(-2)hr(-1) along with an extended
      backwashing of 30 seconds every 3 hours of operation, which maintained the
      transmembrane pressure (TMP) below 100 kPa. Using a simulated municipal
      wastewater with varying phenol concentrations, the chemical oxygen demand (COD)
      and phenol removals observed were greater than 88% with excellent suspended
      solids (SS) removal of 100% at low phenol concentrations (approx. 100 mg l(-1) of
      phenol). Step increases in phenol concentration showed that inhibition was
      observed between 600 to 800 mg l(-1) of phenol with decreased sludge production
      rate, mixed liquor suspended solids (MLSS) concentration, and removal
      performance. The sludge volume index (SVI) of the biomass increased to about 450
      ml g(-1) for a phenol input concentration of 800 mg l(-1). When the phenol
      concentration was decreased to 100 mg l(-1), the ceramic tubular MBR was found to
      recover rapidly indicating that the MBR is a robust system retaining most of the
      biomass. Experimental runs using wastewater containing phenol indicated that the
      MBR can be operated safely without upsets for concentrations up to 600 mg l(-1)
      of phenol at 2-4 hours HRT and 30 days SRT.

PMID- 18613622
TI  - Ultraviolet (UV) disinfection of grey water: particle size effects.
AB  - The impact of water quality on the ultraviolet (UV) disinfection of grey water
      was investigated with reference to urban water reuse. Direct UV disinfection of
      grey water did not meet the stringent California State Title 22 criteria for
      unrestricted urban water reuse due to the presence of particulate material
      ranging from < 1 to > or = 2000 microm in size. Grey water was manipulated by
      settling to produce fractions of varying particle size distributions and blending
      was employed post-disinfection to extract particle-associated coliforms (PACs).
      The efficacy of UV disinfection was found to be linked to the particle size of
      the grey water fractions. The larger particle size fractions with a mean particle
      size of 262 microm and above were observed to shield more coliforms from UV light
      than did the smaller particles with a mean particle size below 119 microm. Up to
      70% of total coliforms in the larger particle size fractions were particle
      associated following a UV dose (fluence) of 260 mJ.cm(-2) and would remain
      undetected by standard coliform enumeration techniques. Implications for urban
      water reuse are discussed and recommendations made for grey water treatment to
      ensure removal of particle-associated indicator bacteria and pathogens prior to
      UV disinfection.

PMID- 18613623
TI  - More than superstition: differential effects of featural heterogeneity and change
      on subitizing and counting.
AB  - This study investigates the effects of item heterogeneity (differences in color
      and shape) and moment-to-moment feature change as it relates to the issue of
      whether subitizing and counting involve different processes. Participants
      enumerated displays of up to eight items that were either homogeneous or
      heterogeneous. In situations where the heterogeneous displays always had
      approximately half of the items of one type and half of the other, heterogeneity
      significantly sped enumeration in the counting range (6-8 items) and
      significantly slowed enumeration in the subitizing range (1-3 items), a
      dissociation that suggests that subitizing and counting involve different
      operations. Moment-to-moment feature change had no effect on subitizing. However,
      feature change slowed counting, but only when participants were enumerating
      heterogeneous items that were half of one type and half of the other, as might be
      expected if participants were using differences in features to select items by
      type.

PMID- 18613624
TI  - A general area theorem for the same-different paradigm.
AB  - According to a well-known theorem in psychophysics (Green & Swets, 1966), the
      area under the receiver operating characteristic (ROC) for the yes-no paradigm
      equals the proportion of correct responses of an unbiased observer in the two
      interval, two-alternative, forced choice paradigm (2I2AFC). Here, we demonstrate
      a similar relationship between the ROC area in the two-interval same-different
      (AX or 2IAX) paradigm, and the proportion correct in the four-interval same
      different (4IAX, also known as dual-pair comparison) paradigm. The theorem
      demonstrated here is general, in the sense that it does not require that the
      sensory observations have a specific distribution (e.g., Gaussian), or that they
      be statistically independent.

PMID- 18613625
TI  - Tactile--visual temporal ventriloquism: no effect of spatial disparity.
AB  - Participants made visual temporal order judgments (TOJs) about which of two
      lights appeared first while task-irrelevant vibrotactile stimuli delivered to the
      index finger were presented before the first and after the second light.
      Temporally misaligned tactile stimuli captured the onsets of the lights, thereby
      improving sensitivity on the visual TOJ task, indicative of tactile-visual (TV)
      temporal ventriloquism (Experiment 1). The size of this effect was comparable to
      auditory-visual (AV) temporal ventriloquism (Experiment 2). Spatial discordance
      between the TV stimuli, as in the AV case, did not harm the effect (Experiments 3
      and 4). TV stimuli thus behaved like AV stimuli, demonstrating that spatial co
      occurrence is not a necessary constraint for intersensory pairing to occur.

PMID- 18613626
TI  - Better than average: alternatives to statistical summary representations for
      rapid judgments of average size.
AB  - People can perceive the individual features of an object by focusing attention on
      it and binding the features together at a location. Some perceptual processing
      can occur without focusing attention on each object, though; people may even be
      able to extract summary information about the sizes of all the objects in a
      display, essentially computing the mean size at a glance. Evidence that people
      can judge the mean size of an array efficiently and accurately has been used to
      support the strong claim that people use a global, parallel process to extract a
      statistical summary of the average size of the objects in the display. Such
      claims are based both on the accuracy of performance and on the supposition that
      performance exceeds what would be possible with serial, focused attention.
      However, these studies typically have not examined the limits of performance with
      focused-attention strategies. Through experiments and simulations, we show that
      existing evidence for mean size perception can be explained through various
      focused-attention strategies, without appealing to a new mechanism of average
      size perception. Although our evidence does not eliminate the possibility that
      people do perceive the average size of all the objects in a display, it suggests
      that simpler mechanisms can accommodate the existing data.

PMID- 18613627
TI  - Attention modulates set representation by statistical properties.
AB  - Recent reports have claimed that observers show accurate knowledge of the mean
      size of a group of similar objects, a finding that has been interpreted to
      suggest that sets of multiple objects are represented in terms of their
      statistical properties, such as mean size (Ariely, 2001; Chong & Treisman, 2003,
      2005a, 2005b). In the present study, we directed visual attention to a single set
      member and found that mean estimations were modulated according to the size of
      the attended item, regardless of whether size was the relevant search criterion
      (Experiment 1) or not (Experiment 2). These findings suggest that observers do
      not always accurately average together the entire set, and that instead the
      average is either biased by the features of the attended item, or based on a
      short-cut strategy of extracting the mean of a smaller subset.

PMID- 18613628
TI  - The effect of attentional demands on the antisaccade cost.
AB  - In the present study, we examined the effect of attentional demands on the
      antisaccade cost (the latency difference between antisaccades and prosaccades).
      Participants performed a visual search for a target digit and were required to
      execute a saccade toward (prosaccade) or away from (antisaccade) the target. The
      results of Experiment 1 revealed that the antisaccade cost was greater when the
      target was premasked (i.e., presented through the removal of line segments) than
      when it appeared as an onset. Furthermore, in premasked target conditions, the
      antisaccade cost was increased by the presentation of onset distractors. The
      results of Experiment 2 revealed that the antisaccade cost was greater in a
      difficult search task (a numeral 2 among 5s) than in an easy one (a 2 among 7s).
      The findings provide evidence that attentional demands increase the antisaccade
      cost. We propose that the attentional demands of the search task interfere with
      the attentional control required to select the antisaccade goal.

PMID- 18613629
TI  - Visuotactile apparent motion.
AB  - This article compares the properties of apparent motion between a light and a
      touch with apparent motion between either two lights or two touches. Visual and
      tactile stimulators were attached to the tips of the two index fingers that were
      held apart at different distances. Subjects rated the quality of apparent motion
      between each stimulus combination for a range of stimulus onset asynchronies
      (SOAs). Subjects reported perceiving apparent motion between all three stimulus
      combinations. For light-light visual apparent motion, the preferred SOA and the
      direction threshold SOAs increased as the distance between the stimuli increased
      (consistent with Korte's third law of apparent motion). Touch-touch apparent
      motion also obeyed Korte's third law, but over a smaller range of distances,
      showing that proprioceptive information concerning the position of the fingers is
      integrated into the tactile motion system. The threshold and preferred SOAs for
      visuotactile apparent motion did not vary with distance, suggesting a different
      mechanism for multimodal apparent motion.

PMID- 18613630
TI  - Time course of grouping of shape by perceptual closure: effects of spatial
      proximity and collinearity.
AB  - We examined time course of grouping of shape by perceptual closure in three
      experiments using a primed matching task. The gaps between the closure-inducing
      contours varied in size. In addition, depending on the distribution of the gaps
      along the closure-inducing contours--occurring at straight contour segments or at
      the point of change in contour direction--collinearity was either present or
      absent. In the absence of collinearity, early priming of the shape was observed
      for spatially close fragments, but not for spatially distant fragments. When
      collinearity was available, the shape of both spatially close and spatially
      distant fragments was primed at brief exposures. These results suggest that
      spatial proximity is critical for the rapid grouping of shape by perceptual
      closure in the absence of collinearity, but collinearity facilitates the rapid
      grouping of shape when the closure-inducing fragments are spatially distant. In
      addition, shape priming persisted over time only when the collinear fragments
      were spatially close, suggesting that a stable representation of shape depends
      both on collinearity and spatial proximity between the closure-inducing
      fragments.

PMID- 18613631
TI  - A scaling analysis of the snake lightness illusion.
AB  - Logvinenko and Maloney (2006) measured perceived dissimilarities between
      achromatic surfaces placed in two scenes illuminated by neutral lights that could
      differ in intensity. Using a novel scaling method, they found that
      dissimilarities between light surface pairs could be represented as a weighted
      linear combination of two dimensions, "surface lightness" (a perceptual correlate
      of the difference in the logarithm of surface albedo) and "surface brightness"
      (which corresponded to the differences of the logarithms of light intensity
      across the scenes). Here we attempt to measure the contributions of these
      dimensions to a compelling lightness illusion (the "snake illusion"). It is
      commonly assumed that this illusion is a result of erroneous segmentation of the
      snake pattern into regions of unequal illumination. We find that the illusory
      shift in the snake pattern occurs along the surface lightness dimension, with no
      contribution from surface brightness. Thus, even if an erroneous segmentation of
      the snake pattern into strips of unequal illumination does happen, it reveals
      itself, paradoxically, as illusory changes in surface lightness rather than as
      surface brightness. We conjecture that the illusion strength depends on the
      balance between two groups of illumination cues signaling the true (uniform)
      illumination and the pictorial (uneven) illumination.

PMID- 18613632
TI  - Tonal expectations influence pitch perception.
AB  - In this study, we investigated the influence of tonal relatedness on pitch
      perception in melodies. Tonal expectations for target tones were manipulated in
      melodic contexts while controlling sensory expectations, thus allowing us to
      assess specifically the influence oftonal expectations on pitch perception. Three
      experimentsprovided converging evidence that tonal relatedness modulates pitch
      perception in nonmusician listeners. Experiment 1 showed, with a rating task, the
      influence of the tonal relatedness of a target tone on listeners' judgments of
      tuning/mistuning. Experiment 2 showed, with a priming task, that pitch processing
      of in-tune tones was faster for tonally related targets than for less related
      targets. Experiment 3 showed, with a comparison task, that discrimination
      performance for small mistunings was better when the to-be-compared tones were
      tonally related to the melodic context. Findings are discussed in relation to
      psychoacoustic research on contextual pitch perception and to studies showing
      facilitation of early processing steps via knowledge- and attention-related
      processes.

PMID- 18613633
TI  - Using morphs of familiar objects to examine how shape discriminability influences
      view sensitivity.
AB  - We investigated how the difficulty of detecting a shape change influenced the
      achievement of object constancy across depth rotations for object identification
      and categorization tasks. In three sequential matching experiments, people saw
      pictures of morphs between two everyday, nameable objects (e.g., bath-sink
      morphs, along a continuum between "bath" and "sink" end-point shapes). In each
      experiment, both view changes and shape changes influenced performance.
      Furthermore, the deleterious effects of view changes were strongest when shape
      discrimination was hardest. In our earlier research, using morphs of novel
      objects, we found a similar interaction between view sensitivity and shape
      sensitivity (Lawson, 2004b; Lawson & Bulthoff, 2006; Lawson, Bulthoff, & Dumbell,
      2003). The present results extend these findings to familiar-object morphs. They
      suggest that recognition remains view-sensitive at the basic level of
      identification for everyday, nameable objects, and that the difficulty of shape
      discrimination plays a critical role in determining the degree of this view
      sensitivity.

PMID- 18613634
TI  - Constant versus variable response signal delays in speed--accuracy trade-offs:
      effects of advance preparation for processing time.
AB  - In two experiments, we used response signals (RSs) to control processing time and
      trace out speed--accuracy trade-off(SAT) functions in a difficult perceptual
      discrimination task. Each experiment compared performance in blocks of trials
      with constant and, hence, temporally predictable RS lags against performance in
      blocks with variable, unpredictable RS lags. In both experiments, essentially
      equivalent SAT functions were observed with constant and variable RS lags. We
      conclude that there is little effect of advance preparation for a given
      processing time, suggesting that the discrimination mechanisms underlying SAT
      functions are driven solely by bottom-up information processing in perceptual
      discrimination tasks.

PMID- 18613635
TI  - Grouping in the shine-through effect.
AB  - How the elements of a visual scene are grouped into objects is one of the most
      fundamental but still poorly understood questions in visual neuroscience. Most
      investigations of perceptual grouping focus on static stimuli, neglecting
      temporal aspects. Using a masking paradigm, we show that the neural mechanisms
      underlying grouping seem to be both fast and complex. For example, a vernier
      target was followed by, first, a briefly presented grating and, then, a long
      lasting, extended grating. Under these conditions, the briefly presented grating
      is hardly visible. Still, vernier discrimination strongly changed with the number
      of elements of the briefly displayed grating being worst for small gratings. In
      accordance with a neural network model of masking, we propose that the edges of
      the briefly presented grating and the vernier interfere in spite of the short
      presentation time. We suggest that this fast edge processing is a first step for
      unconscious grouping processes.

PMID- 18613636
TI  - Object file continuity and the auditory attentional blink.
AB  - Three experiments were designed to investigate the causes of the auditory
      attentional blink (AB). Experiments 1A and 1B revealed that there was a larger
      auditory AB when the target and the distractors were different in two attributes
      than when they were different in only one attribute. Experiments 2A and 2B showed
      that for pure-tone distractor sequences, there were small auditory AB deficits
      when both the target and the probe were different from the distractors in two
      attributes or in one attribute; however, for pulse distractor sequences, there
      was a large auditory AB when both the target and the probe were different from
      the distractors in one attribute, but not when they were different in two
      attributes. Experiments 3A and 3B revealed that regardless of the relationship of
      the target to the subsequent distractors, a large AB was generated if it was the
      first sound in a sequence. Moreover, only a very small AB was apparent when the
      distractors following the probe were replaced by silence. These results indicated
      that the auditory AB is affected by both the requirement of creating and
      consolidating a new object file for the target and the overwriting of the probe
      by the distractors following it.

PMID- 18613637
TI  - Spatial working memory load impairs signal enhancement, but not attentional
      orienting.
AB  - The present study examined the effect of spatial working memory load on the
      attentional cuing effect. It is well-known that spatial working memory and
      spatial attention functionally overlap or share a common resource. Given this
      functional overlapping, it is possible that spatial working memory would also
      interact with the attentional cuing effect. Considering the distinction between
      channel selection and channel enhancement by attention (Prinzmetal, McCool, &
      Park, 2005), we expected that the interaction between spatial working memory and
      the cuing effect would differ with attentional processing type. Two experiments
      conducted with the spatial cuing paradigm showed that the magnitude of the cuing
      effect as measured by reaction time, reflecting channel selection, was
      uninfluenced by spatial working memory load. In contrast, spatial working memory
      load reduced the cuing effect as measured by accuracy, reflecting channel
      enhancement. These results suggest that spatial working memory load impairs
      signal enhancement by attention and does not influence attentional orienting per
      se. The interaction between spatial working memory and visual perception is also
      discussed.

PMID- 18613638
TI  - Stressing the mind: the effect of cognitive load and articulatory suppression on
      attentional guidance from working memory.
AB  - Four experiments explored the effect of cognitive load on the time course of top
      down guidance of attention from working memory (WM). Observers had to search for
      a target presented among several distractors, with the target and distractor
      stimuli embedded inside different objects. On half of the trials, one of the
      distractor objects was cued by a matching item held in WM. When a single item was
      maintained in memory, search performance was impaired relative to a neutral
      baseline, where the memory and search displays did not match. These effects of WM
      on subsequent search were reduced by including a verbal suppression task during
      the WM and search displays, and by varying the WM load. The degree of competition
      for resources in WM is a key factor in determining the time course and magnitude
      of the interaction between WM and visual selection.

PMID- 18613639
TI  - History of the membrane (pump) theory of the living cell from its beginning in
      mid-19th century to its disproof 45 years ago--though still taught worldwide
      today as established truth.
AB  - The concept that the basic unit of all life, the cell, is a membrane-enclosed
      soup of (free) water, (free) K+ (and native) proteins is called the membrane
      theory. A careful examination of past records shows that this theory has no
      author in the true sense of the word. Rather, it grew mostly out of some mistaken
      ideas made by Theodor Schwann in his Cell Theory. (This is not to deny that there
      is a membrane theory with an authentic author but this authored membrane theory
      came later and is much more narrowly focussed and accordingly can at best be
      regarded as an offshoot of the broader and older membrane theory without an
      author.) However, there is no ambiguity on the demise of the membrane theory,
      which occurred more than 60 years ago, when a flood of converging evidence showed
      that the asymmetrical distribution of K+ and Na+ observed in virtually all living
      cells is not the result of the presence of a membrane barrier that permits some
      solutes like water and K+ to move in and out of the cell, while barring-
      absolutely and permanently--the passage of other solutes like Na+. To keep the
      membrane theory afloat, submicroscopic pumps were installed across the cell
      membrane to maintain, for example, the level of Na+ in the cell low and the level
      of K+ high by the ceaseless pumping activities at the expense of metabolic
      energy. Forty-five year ago this version of the membrane theory was also
      experimentally disproved. In spite of all these overwhelming evidence against the
      membrane-pump theory, it still is being taught as verified truth in all high
      school and biology textbooks known to us today. Meanwhile, almost unnoticed, a
      new unifying theory of the living cell, called the association-induction
      hypothesis came into being some 40 years ago. Also little noticed was the fact
      that it has received extensive confirmation worldwide and has shown an ability to
      provide self-consistent interpretations of most if not all known experimental
      observations that are contradicting the membrane-pump theory as well as other
      observations that seem to support the membrane pump theory.

PMID- 18613640
TI  - Regulation of 5-aminolevulinic acid-dependent protoporphyrin IX accumulations in
      human histiocytic lymphoma U937 cells.
AB  - The aim of the present work is to clarify the mechanism(s) that regulates the
      accumulation of protoporphyrin IX (PpIX) in human histiocytic lymphoma cell line
      U937 incubated with 5-aminolevulinic acid (ALA). Biosynthesis and accumulation of
      PpIX in the cells was determined after incubation with 0.1-5 mM ALA using a flow
      cytometric technique. The synthesized endogenous PpIX was found to localize
      predominantly in the mitochondrial region of the cells. The ALA-enhanced PpIX
      synthesis was suppressed by the presence of either beta-alanine, a competitive
      inhibitor of beta-transporters on cell membranes, or carbonyl cyanide p
      trifluoromethoxyphenyl hydrazone, an uncoupler of mitochondrial oxidative
      phosphorylation. In contrast, cellular accumulation of PpIX was enhanced by the
      presence of either deferoxamine (an iron chelater), MnCl2 (a ferrochelatase
      inhibitor), or Sn-mesoporphyrin (heme oxygenase inhibitor). These results suggest
      that ALA-enhanced accumulation of PpIX in U937 cells was regulated by cellular
      uptake and conversion of ALA to PpIX and by degradation of Heme.

PMID- 18613641
TI  - Exposure to an additional alternating magnetic field affects comb building by
      worker hornets.
AB  - Oriental hornet workers, kept in an Artificial Breeding Box (ABB) without a
      queen, construct within a few days brood combs of hexagonal cells with apertures
      facing down. These combs possess stems that fasten the former to the roof of the
      ABB. In an ABB with adult workers (more than 24 h after eclosion), exposed to an
      AC (50 Hz) magnetic field of a magnitude of B = 50-70 mGauss, the combs and cells
      are built differently from those of a control ABB, subjected only to the natural
      terrestrial magnetic field. The effects of the additional magnetic field consist
      of (a) 35-55% smaller number of cells and fewer eggs in each comb, (b) disrupted
      symmetry of building, with many deformed and imperfectly hexagonal cells, and (c)
      more delicate and slender comb stems.

PMID- 18613642
TI  - An unanswered 2003 letter appealing on behalf of all mankind to Nobel Laureate
      Roderick McKinnon to use his newfound fame and visibility to begin restoring
      honesty and integrity to basic biomedical science by rebutting or correcting
      suspected plagiarism in his Nobel-Prize-winning work.
AB  - The centerpiece of this document is an unanswered letter of appeal from the
      author to Professor Roderick MacKinnon of the Rockefeller University dated
      November 17, 2003. The aim of the appeal is summarized in the title of this
      communication. In addition to the 2003 letter, there are also two follow-up
      letters in this communication, each containing a copy of the 2003 letter and each
      repeating the appeal. The follow-up letters, dated February 22, 2008 and April 2,
      2008 respectively, were also unanswered. To make sure that these letters reached
      their destination, each was certified with delivery time and date affirmed. Thus
      the February 22 letter was delivered on the February 24 by the US Postal Service.
      Two copies of the April 2 follow-up letter were sent. The first copy was
      delivered by Federal Express on April 4. The second copy of the April 2 letter
      was delivered by the US Postal Service on the same day. Thus all told three
      additional copies of the 2003 letters were delivered to, and must be in the hand
      of Professor MacKinnnon. All these efforts were made to make certain that
      Professor MacKinnon's refusal to answer my registered 2003 letter was not due to
      his not having received a copy of that letter.

PMID- 18613643
TI  - Identical twins, asymmetrical mitosis and bilateral symmetry of organisms.

PMID- 18613644
TI  - Activation of NK cells by extracellular heat shock protein 70 through induction
      of NKG2D ligands on dendritic cells.
AB  - We have previously reported that heat shock protein 70 (HSP70) vaccination
      induced natural killer (NK) cell activity in patients with chronic myelogenous
      leukemia (CML). In this study, HSP70 of both autologous and allogeneic origin was
      found to stimulate IFN-gamma production from peripheral blood mononuclear cells
      of CML patients, as well as of normal subjects. Further investigations
      demonstrated that the activity of HSP70 was dependent on both NK cells and
      dendritic cells (DCs). HSP70 did not induce significant IFN-gamma production from
      either NK cells or DCs alone. Mechanistically, we found that HSP70-mediated DC-NK
      cell crosstalk required cell-cell contact, which could be inhibited completely by
      neutralizing antibody against NK activating receptor NKG2D. The significance of
      NKG2D was further corroborated by the finding that HSP70 induced the expression
      of an NKG2D ligand, the MHC class I chain-related protein A (MICA), on DCs; HSP70
      augmented IFN-gamma release was abrogated by antibody against MICA. Thus
      extracellular HSP70, released during either stress or inflammatory cell death,
      may serve as a critical link between NK and DCs in mounting immune responses
      against infections, cancers and self-antigens.

PMID- 18613645
TI  - Capillary electrophoresis time-of-flight mass spectrometry for comparative
      metabolomics of transgenic versus conventional maize.
AB  - In this work, capillary electrophoresis time-of-flight mass spectrometry (CE-TOF
      MS) is proposed to identify and quantify the main metabolites in three lines of
      genetically modified (GM) maize and their corresponding nontransgenic parental
      lines grown under identical conditions. The shotgun-like approach for
      metabolomics developed in this work includes optimization of metabolite
      extraction from GM and non-GM maize, separation by CE, online electrospray-TOF-MS
      analysis, and data evaluation. A large number of extraction procedures and
      background electrolytes are tested in order to obtain a highly reproducible and
      informative metabolomic profile. Thus, using this approach, significant
      differences were systematically observed between the detected amounts of some
      metabolites in conventional varieties (Aristis, Tietar, and PR33P66 maize)
      compared with their corresponding transgenic lines (Aristis Bt, Tietar Bt, and
      PR33P66 Bt maize). Results point to some of these metabolites as possible
      biomarkers of transgenic Bt maize, although a larger number of samples needs to
      be analyzed in order to validate this point. It is concluded that metabolomics
      procedures based on CE-TOF-MS can open new perspectives in the study of
      transgenic organisms in order to corroborate (or not) their substantial
      equivalence with their conventional counterparts.

PMID- 18613646
TI  - Analytical advantages of multivariate data processing. One, two, three, infinity?
AB  - Multidimensional data are being abundantly produced by modern analytical
      instrumentation, calling for new and powerful data-processing techniques.
      Research in the last two decades has resulted in the development of a multitude
      of different processing algorithms, each equipped with its own sophisticated
      artillery. Analysts have slowly discovered that this body of knowledge can be
      appropriately classified, and that common aspects pervade all these seemingly
      different ways of analyzing data. As a result, going from univariate data (a
      single datum per sample, employed in the well-known classical univariate
      calibration) to multivariate data (data arrays per sample of increasingly complex
      structure and number of dimensions) is known to provide a gain in sensitivity and
      selectivity, combined with analytical advantages which cannot be overestimated.
      The first-order advantage, achieved using vector sample data, allows analysts to
      flag new samples which cannot be adequately modeled with the current calibration
      set. The second-order advantage, achieved with second- (or higher-) order sample
      data, allows one not only to mark new samples containing components which do not
      occur in the calibration phase but also to model their contribution to the
      overall signal, and most importantly, to accurately quantitate the calibrated
      analyte(s). No additional analytical advantages appear to be known for third
      order data processing. Future research may permit, among other interesting
      issues, to assess if this "1, 2, 3, infinity" situation of multivariate
      calibration is really true.

PMID- 18613647
TI  - Validated comprehensive analytical method for quantification of coenzyme A
      activated compounds in biological tissues by online solid-phase extraction
      LC/MS/MS.
AB  - We report a robust, reliable, and comprehensive analytical method for the
      identification and quantification of the entire class of coenzyme A (CoA)
      activated substances, particularly short-, medium-, and long-chain acyl-CoAs
      derived from various biological tissues. This online SPE-LC/MS/MS-based method is
      characterized by a simple three-step sample preparation: (1) addition of buffer,
      organic solvents, and internal standards; (2) homogenization; and (3)
      centrifugation. The supernatant is injected directly into the SPE-LC/MS/MS
      system. Identification of CoA activated compounds is performed by accurate mass
      determination within the HPLC run. Method validation for short-, medium-, and
      long-chain acyl-CoA fatty acids revealed excellent quality. Accuracy was found to
      be between 87 and 107% and precision was between 0.1 and 12.8% in mouse skeletal
      muscle. The lower limit of quantification for all investigated compounds was well
      below 3.1% of estimated physiological levels in 200 mg of mouse tissue.
      Comparable results were obtained for mouse liver, mouse brown white adipose
      tissue and rat liver. For all investigated tissues, no matrix effect was
      observed.

PMID- 18613648
TI  - Role of fluorosurfactant-modified gold nanoparticles in selective detection of
      homocysteine thiolactone: remover and sensor.
AB  - In this article, we report a simple approach for the selective sensing of
      homocysteine thiolactone (HTL) using fluorosurfactant (FSN)-capped gold
      nanoparticles (AuNPs) as aminothiol removers and as sensors. We have shown that
      HTL did not bind to the surface of the FSN-AuNPs in the pH range of 4.0-10.0. In
      contrast, under these pH conditions, the FSN-AuNPs are aggregated upon the
      addition of homocysteine (HCys) and cysteine (Cys). On the basis of this feature,
      we have demonstrated that FSN-AuNPs are effective sorbent materials for HCys and
      Cys, but not for HTL. It is found that the FSN-AuNPs can remove of >98% of HCys
      and >99% of Cys from an aqueous solution. Thus, after the centrifugation of a
      solution containing AuNPs, HTL, and other aminothiols, only HTL remains in the
      supernatant. When NaOH is added to the supernatant, HTL is hydrolyzed to HCys,
      leading to the aggregation of the FSN-AuNPs. As a result, the selectivity of the
      probe is significantly higher for HTL in aqueous solutions than for other
      aminthiols. The sensitivity of FSN-AuNPs toward HTL can be further improved by
      optimizing the AuNP concentrations. Under optimum conditions, the lowest
      detectable concentration of HTL through this approach is 100 nM. We have
      validated the applicability of our method through the analyses of HTL in urine
      samples.

PMID- 18613649
TI  - Conformational change detection in nonmetal proteins by direct electrochemical
      oxidation using diamond electrodes.
AB  - In this report, we established a new electrochemical method for the detection of
      conformational changes in large, non-metalloproteins such as bovine serum
      albumin, using flow injection analysis coupled with hydrogen-terminated, boron
      doped diamond electrodes. The oxidation current was used as a signal reporter in
      the monitoring of urea-induced BSA denaturation. In the denatured state at high
      urea concentrations, the electrochemical signal increased, and the amperometric
      responses for the oxidation potential at 1300 mV were consistent with the results
      of conventional methods of denaturation monitoring using fluorescence
      spectroscopy. The oxidation involved at least five redox-active species
      (cysteine, tryptophan, tyrosine, methionine, and disulfide bonds). Furthermore,
      the method also showed high sensitivity for quantitative analysis of protein. A
      linear dynamic in the concentration range 50-400 microg/mL (r(2) = 0.977) with a
      lower detection limit of 190 ng/mL was achieved for BSA. Direct electrochemical
      detection of conformation changes of proteins using BDD electrodes can be
      performed with advantages in terms of simplicity and sensitivity.

PMID- 18613650
TI  - Ultratrace uranium fingerprinting with isotope selective laser ionization
      spectrometry.
AB  - Uranium isotope ratios can provide source information for tracking uranium
      contamination in a variety of fields, ranging from occupational bioassay to
      monitoring aftereffects of nuclear accidents. We describe the development of
      isotope selective laser ionization spectrometry for ultratrace measurement of the
      minor isotopes (234)U, (235)U, and (236)U with respect to (238)U. The inherent
      isotopic selectivity of three-step excitation with single-mode continuous wave
      lasers results in measurement of the minor isotopes at relative abundances below
      1 ppm and is not limited by isobaric interferences such as (235)UH(+) during
      measurement of (236)U. This relative abundance limit is attained without mass
      spectrometric analysis of the laser-created ions. Uranyl nitrate standards from
      an international blind comparison were used to test analytical performance for
      different isotopic compositions and with quantities ranging from 11 ng to 10
      microg total uranium. Isotopic ratio determination was demonstrated over a linear
      dynamic range of 7 orders of magnitude with a few percent relative precision and
      detection limits below 500 fg for the minor isotopes.

PMID- 18613651
TI  - Assembly-disassembly of DNAs and gold nanoparticles: a strategy of intervention
      based on oligonucleotides and restriction enzymes.
AB  - The ability to manipulate and intervene in the processes of assembly and
      disassembly of DNAs and nanoparticles is important for the exploitation of
      nanoparticles in medical diagnostics and drug delivery. This report describes the
      results of an investigation of a strategy to intervene in the assembly and
      disassembly processes of DNAs and gold nanoparticles based on two approaches. The
      first approach explores the viability of molecular intervention to the assembly
      disassembly-reassembly process. The temperature-induced assembly and disassembly
      processes of DNAs and gold nanoparticles were studied as a model system to
      illustrate this approach. The introduction of a molecular recognition probe leads
      to intervention in the assembly-disassembly process depending on its specific
      biorecognition. This process was detected by monitoring the change in the optical
      properties of gold nanoparticles and their DNA assemblies. The second approach
      involves the disassembly of the DNA-linked assembly of nanoparticles using
      restriction enzymes (e.g., MspI). The presence of the double stranded DNAs in the
      nanoparticle assembly was also substantiated by a Southern blot. Implications of
      the results to exploration of the molecular intervention for fine-tuning
      interfacial reactivities in DNA-based bioassays are also discussed.

PMID- 18613652
TI  - Investigation on critical aggregation concentration of carbosiloxane dendrimer in
      dilute solution probed by rhodamine B.
AB  - We propose a novel method for probing aggregation of dendrimers by investigating
      the isomerization equilibrium between pink zwitterionic form (Z-form) and
      colorless lactonic form (L-form) of rhodamine B (RhB) molecules in dilute
      solution. Investigation using carbosiloxane dendrimers (CSiO-D) with different
      generations as the model dendrimer molecules showed that the equilibrium constant
      of isomerization of RhB increased dramatically at the critical aggregation
      concentration (CAC) of dendrimers. The redox potential differences between
      isomers of RhB indicated that aggregation of CSiO-D accelerated the isomerization
      of RhB and stabilized the L-form of RhB. The data on Gibbs energy and
      electrolytic conductivity provided further evidence for confirming the CAC of
      dendrimers in dilute solution and showed good agreement with our other
      experimental results. The proposed method is effective in estimating the CAC of
      dendrimers in dilute solution.

PMID- 18613653
TI  - Conjugation and hyperconjugation in conformational analysis of cyclohexene
      derivatives containing an exocyclic double bond.
AB  - The equilibrium geometry, ring-inversion pathway barriers for analogues of
      cyclohexene with an exocyclic double bond have been studied using the MP2/6-311
      G(d,p) level of theory. The equilibrium conformation of the ring depends on
      conjugation between the endocyclic and exocyclic double bonds. Interactions
      between conjugated double bonds include the pi-pi conjugation and interactions
      between the lone pair of the heteroatom of the exocyclic double bond and the
      sigma-antibonding orbital of the endocyclic single bond. In the case of the
      tetrahydrocycles with double bonds separated by a methylene group the balance
      between the pi --> sigma* hyperconjugation interactions between the exocyclic
      double bond and the neighboring methylene group and the n --> sigma* interaction
      between the lone pair of the heteroatom and the sigma-antibonding orbitals of the
      C(sp(2))-C(sp(3)) bond determine the geometrical parameters of the ring. The
      character of the potential-energy surface around the saddle point depends on the
      position of the exocyclic double bond and the orientation of the hydrogen atom
      attached to the heteroatom of the V group of the periodic table in the
      tetrahydrocycles with double bonds separated by a methylene group.

PMID- 18613654
TI  - Isomerization and decomposition reactions in the pyrolysis of branched
      hydrocarbons: 4-methyl-1-pentyl radical.
AB  - The kinetics of the decomposition of 4-methyl-1-pentyl radicals have been studied
      from 927-1068 K at pressures of 1.78-2.44 bar using a single pulse shock tube
      with product analysis. The reactant radicals were formed from the thermal C-I
      bond fission of 1-iodo-4-methylpentane, and a radical inhibitor was used to
      prevent interference from bimolecular reactions. 4-Methyl-1-pentyl radicals
      undergo competing decomposition and isomerization reactions via beta-bond
      scission and 1, x-hydrogen migrations (x = 4, 5), respectively, to form short
      chain radicals and alkenes. Major alkene products, in decreasing order of
      concentration, were propene, ethene, isobutene, and 1-pentene. The observed
      products are used to validate a RRKM/master equation (ME) chemical kinetics model
      of the pyrolysis. The presence of the branched methyl moiety has a significant
      impact on the observed reaction rates relative to analogous reaction rates in
      straight-chain radical systems. Systems that result in the formation of
      substituted radical or alkene products are found to be faster than reactions that
      form primary radical and alkene species. Pressure-dependent reaction rate
      constants from the RRKM/ME analysis are provided for all four H-transfer isomers
      at 500-1900 K and 0.1-1000 bar pressure for all of the decomposition and
      isomerization reactions in this system.

PMID- 18613655
TI  - Experimental and theoretical studies on the complexes of [Pb(m)-pyridyl]- (m = 1
      4).
AB  - The pyridyl-lead complexes [Pb(m)-C5H4N](-) (m = 1-4), which are produced from
      the reactions between lead clusters formed by laser ablation and the pyridine
      molecules seeded in argon carrier gas, are studied by photoelectron (PE) spectra
      and density functional theory. The adiabatic electron affinity (EA) of
      [Pb(m)C5H4N](-) is obtained from PE spectra at photon energies of 308 and 193 nm.
      Theoretical calculation is carried out to elucidate their structures and bonding
      modes. A variety of geometries for the isomers are optimized to search for the
      lowest-energy geometry. By comparing the theoretical results, including the EA
      and simulated density of state spectra, with the experimental determination, the
      lowest-energy structures for each species are obtained. The following analysis of
      the molecular orbital composition provides the evidence that the pyridyl binds on
      lead clusters through the Pb-C sigma bond. Moreover, there is an apparent spin
      state transition from triplet state toward singlet state for the ground-state
      structure of [Pb(m)C5H4N](-) with an increase of lead cluster.

PMID- 18613656
TI  - Systematic study of the influence of base-step parameters on the electronic
      coupling between base-pair dimers: comparison of A-DNA and B-DNA forms.
AB  - The electronic coupling is one of the key parameters governing electron hole
      transfer along DNA helices. In this study, we established the first comprehensive
      data base of electronic coupling elements, calculated at the ab initio level. The
      data set comprises all possible Watson-Crick base pair dimers, both in standard A
      DNA and B-DNA geometries. We also quantified the sensitivity of the coupling
      elements with respect to geometry changes by varying each of the six standard
      base step parameters, which specify the relative orientation of neighboring base
      pairs. We compare the couplings in a systematic way by discussing variations in
      the coupling magnitude due to geometry or nucleotide sequence in the dimer, and
      we analyze how the structure affects the electronic coupling in terms of general
      and dimer-specific trends. Furthermore, we studied how the coupling changes when
      one introduces the chemically modified base 7-deazaguanine in the corresponding
      base-pair dimers. Finally, on the basis of the calculated coupling elements, we
      suggest a model duplex with an enhanced capacity for hole transfer.

PMID- 18613657
TI  - Improved description of nuclear magnetic resonance chemical shielding constants
      using the M06-L meta-generalized-gradient-approximation density functional.
AB  - The performance of the M06-L density functional has been tested for four
      databases of NMR isotropic chemical shielding constants. Comparison with the
      B3LYP, BLYP, HCTH, KT1, KT2, LSDA, OPBE, OLYP, PBE, TPSS, and VSXC functionals
      shows that M06-L has improved performance for calculating NMR chemical shielding
      constants, especially for highly correlated systems. We also found that VSXC and
      M06-L have encouraging accuracy for calculating (13)C chemical shielding
      constants, and both functionals perform very well for the chemical shielding
      constants in the o-benzyne molecule.

PMID- 18613658
TI  - Ab initio studies on the photophysics of guanine tautomers: out-of-plane
      deformation and NH dissociation pathways to conical intersections.
AB  - The radiationless decay mechanisms of the S1 excited states of the 7H-keto-amino,
      7H-enol-amino, and 7H-keto-imino tautomers of guanine have been investigated with
      the CASPT2//CASSCF method. Out-of-plane deformation of the six-membered ring or
      the imino group as well as dissociation of NH bonds have been considered as
      photochemical pathways leading to conical intersections with the electronic
      ground state. It has been found that all three tautomers can reach S0-S1 conical
      intersections by out-of-plane deformation. However, only in the 7H-keto-amino
      tautomer the reaction path leading to the conical intersection is barrierless.
      This tautomer also has the lowest energy barrier for hydrogen detachment via the
      (1)pi sigma* state, whose potential energy surface intersects that of the (1)pi
      pi* state as well as that of the ground state. The other tautomers of guanine
      exhibit substantial energy barriers on their S1 potential energy surfaces with
      respect to both reaction mechanisms. These findings suggest that the 7H-keto
      amino tautomer exhibits the shortest excited-state lifetime of the three
      tautomers due to particularly fast nonradiative deactivation processes through S0
      S1 conical intersections. The computational results explain the remarkable
      observation that the energetically most stable 7H-keto-amino tautomer is missing
      in the resonant two-photon ionization spectrum of guanine in a supersonic jet.
      The results also explain that the energetically less stable 7H-enol-amino and 7H
      keto-imino tautomers have longer excited-state lifetimes and are thus detectable
      by resonant two-photon ionization.

PMID- 18613659
TI  - A study of the reactive intermediate IF and I atoms with photoelectron
      spectroscopy.
AB  - Angle-resolved photoelectron (PE) spectra were recorded for IF and I. These were
      prepared as primary and secondary products of the F + CH2I2 reaction. PE spectra
      were recorded with different IF-to-I ratios to evaluate the relative intensities
      of IF and I photoelectron bands where their bands were overlapped. Improved
      values were obtained for the vertical and adiabatic ionization energies of the
      IF(+)(X(2)Pi(3/2)) <-- IF(X(1)sigma(+)) and IF(+)((2)Pi(1/2)) <--
      IF(X(1)sigma(+)) ionizations and for the spectroscopic constants omega(e) and
      omega(e)ex(e) for the two IF ionic states X(2)Pi(3/2) and (2)Pi(1/2). Equilibrium
      bond lengths r(e) of these IF ionic states were derived from the experimental
      relative intensities of the vibrational components and calculated Franck-Condon
      factors. Threshold photoelectron (TPE) spectra were also recorded under the same
      reaction conditions. On comparing the TPE and PE spectra, the contributions from
      atomic iodine were much more intense in the TPE spectra. No difference was seen
      between the vibrational envelopes of the two observed IF bands, and no extra
      structure was seen associated with the TPE bands of IF as has been observed in
      TPE spectra of other diatomic halogens. The extra features that were observed in
      the TPE spectra can be assigned to contributions from autoionization of known I
      Rydberg states.

PMID- 18613660
TI  - Theoretical investigation of nitration and nitrosation of dimethylamine by N2O4.
AB  - Reactive nitrogen oxygen species (RNOS) contribute to the deleterious effects
      attributed to reacting with biomolecules. The mechanisms of the nitration and
      nitrosation of dimethylamine (DMA), which is the simplest secondary amine by
      N2O4, a member of RNOS, have been investigated at the CBS-QB3 level of theory.
      The nitration and nitrosation proceed via different pathways. The nitration of
      DMA follows three pathways. The first is the abstraction of the hydrogen atom of
      the amino group of DMA by the NO2 radical followed by a recombination reaction of
      the resulting aminyl radical with another NO2 radical. The second is DMA directly
      reacting with symmetrical O2NNO2 leading to dimethylnitramine via a concerted and
      a stepwise mechanism. The third is the reaction of DMA with asymmetrical ONONO2.
      By computation, the main pathway for the formation of dimethylnitramine in the
      gas phase is by DMA directly reacting with asymmetrical ONONO2. As to the
      nitrosation, a concerted mechanism for the reaction of DMA with asymmetrical
      ONONO2 plays a major role in nitrosodimethylamine (NDMA) formation. In addition,
      the solvent effect on these nitration and nitrosation reactions has been also
      studied by using the implicit polarizable continuum model. Two major pathways of
      the formation of dimethylnitramine in water were found, and they are the radical
      process involving NO2 and the concerted mechanism starting from symmetrical
      O2NNO2. The result of the nitrosation of DMA in water is consistent with that in
      the gas phase. Comparison of the energy barriers of each mechanism leads to the
      conclusion that the nitrosation is more favorable than the nitration in the
      reaction of DMA with N2O4. This conclusion is in good agreement with the
      experimental results. The results obtained here will help elucidate the mechanism
      of the lesions of biomolecules by RNOS.

PMID- 18613661
TI  - Structure of daidzin, a naturally occurring anti-alcohol-addiction agent, in
      complex with human mitochondrial aldehyde dehydrogenase.
AB  - The ALDH2*2 gene encoding the inactive variant form of mitochondrial aldehyde
      dehydrogenase (ALDH2) protects nearly all carriers of this gene from alcoholism.
      Inhibition of ALDH2 has hence become a possible strategy to treat alcoholism. The
      natural product 7-O-glucosyl-4'-hydroxyisoflavone (daidzin), isolated from the
      kudzu vine ( Peruraria lobata), is a specific inhibitor of ALDH2 and suppresses
      ethanol consumption. Daidzin is the active principle in a herbal remedy for
      "alcohol addiction" and provides a lead for the design of improved ALDH2. The
      structure of daidzin/ALDH2 in complex at 2.4 A resolution shows the isoflavone
      moiety of daidzin binding close to the aldehyde substrate-binding site in a
      hydrophobic cleft and the glucosyl function binding to a hydrophobic patch
      immediately outside the isoflavone-binding pocket. These observations provide an
      explanation for both the specificity and affinity of daidzin (IC50 =80 nM) and
      the affinity of analogues with different substituents at the glucosyl position.

PMID- 18613662
TI  - Mechanistic consequences of composition in acid catalysis by polyoxometalate
      keggin clusters.
AB  - The kinetics and mechanism of ether and alkanol cleavage reactions on Bronsted
      acid catalysts based on polyoxometalate (POM) clusters are described in terms of
      the identity and dynamics of elementary steps and the stability of the transition
      states involved. Measured rates and theoretical calculations show that the
      energies of cationic transition states and intermediates depend on the properties
      of reactants (proton affinity), POM clusters (deprotonation enthalpy), and ion
      pairs in transition states or intermediates (stabilization energy). Rate
      equations and elementary steps were similar for dehydration of alkanols (2
      propanol, 1- and 2-butanol, tert-butanol) and cleavage of sec-butyl-methyl ether
      on POM clusters with different central atoms (P, Si, Co, Al). Dehydration rates
      depend on the rate constant for elimination from adsorbed alkanols or ethers and
      on the equilibrium constant for the formation of unreactive reactant dimers.
      Elimination involves E1 pathways and late carbenium-ion transition states. This
      is consistent with small kinetic isotope effects for all deuterated alkanols,
      with strong effects of substituents on elimination rates, and with the similar
      alkene stereoselectivities measured for alkanol dehydration, ether cleavage, and
      alkene double-bond isomerization. n-Donor reactants (alkanols, ethers) and
      products (water) inhibit dehydration rates by forming stable dimers that do not
      undergo elimination; their stability is consistent with theoretical estimates,
      with the dynamics of homogeneous analogues, and with the structure and proton
      affinity of the n-donors. Elimination rate constants increased with increasing
      valence of the central POM atom, because of a concurrent decrease in
      deprotonation enthalpies (DPE), which leads to more stable anionic clusters and
      ion-pairs at transition states. The DPE of POM clusters influences catalytic
      rates less than the proton affinity of the alkene-like organic moiety at the late
      carbenium-ion-type transition states involved. These different sensitivities
      reflect the fact that weaker acids typically form anionic clusters with a higher
      charge density at the transition state; these clusters stabilize cationic
      fragments more effectively than those of stronger acids, which form more stable
      conjugate bases with lower charge densities. These compensation effects are
      ubiquitous in acid chemistry and also evident for mineral acids. The
      stabilization energy and the concomitant charge density and distribution in the
      anion, but not the acid strength (DPE), determine the kinetic tolerance of n
      donors and the selectivity of reactions catalyzed by Bronsted acids.

PMID- 18613663
TI  - Catalytic asymmetric synthesis of 2,2-disubstituted terminal epoxides via
      dimethyloxosulfonium methylide addition to ketones.
AB  - Catalytic asymmetric Corey-Chaykovsky epoxidation of ketones with
      dimethyloxosulfonium methylide 2 using an LLB 1a + Ar3P O complex proceeded
      smoothly at room temperature, and 2,2-disubstituted terminal epoxides were
      obtained in high enantioselectivity (91-97%) and yield (>88-99%) from a broad
      range of methyl ketones with 1-5 mol % catalyst loading. The use of achiral
      additive Ar3P O 5i was important to achieve high enantioselectivity.

PMID- 18613665
TI  - Planar pentacoordinate carbon in CAl5(+): a global minimum.
AB  - We report evidence for the first global-minimum structure having a planar
      pentacoordinate carbon. High-level ab initio computations and quantum molecular
      dynamics simulations at 300 and 400 K reveal that the most stable CAl5(+) isomer
      has D5h symmetry and is approximately 3.80 kcal/mol lower in energy than the
      second most stable alternative. The latter has a nonplanar structure based on a
      tetrahedral CAl4 moiety. The unexpectedly high proclivity for two-dimensional
      chemical bonding of the carbon in D5h CAl5(+), the robust thermal stability
      indicated computationally, and its mass spectrometric detection suggest that
      experimental characterization of this planar pentacoordinate carbon cation at
      room temperature is a likely prospect.

PMID- 18613666
TI  - Dynamics of excited-state conformational relaxation and electronic delocalization
      in conjugated porphyrin oligomers.
AB  - We have investigated the influence of nuclear geometric relaxation on the extent
      of the excited-state electronic delocalization in conjugated zinc porphyrin
      oligomers using ultrafast transient photoluminescence spectroscopy. By use of
      metal-coordinating templates that force the oligomers into specific geometries in
      solution we are able to distinguish clearly between relaxation effects arising
      from the two vibrational modes that preferentially couple to the electronic
      transitions in such materials, i.e., carbon-carbon bond stretches and inter-ring
      torsions. We find that light absorption generates an excited state that is
      initially strongly delocalized along the oligomer but contracts rapidly following
      vibrational relaxation of the nuclei along C-C stretch coordinates on the
      subpicosecond time scale. We are able to monitor such excitonic self-trapping
      effects by observing the extent to which the concomitant ultrafast rotation of
      the transition dipole moment is found to correlate with the degree of bending
      induced in the molecular backbone. We further demonstrate that interporphyrin
      torsional relaxation leads to a subsequent increase in the excited-state
      electronic delocalization on a longer time scale (approximately 100 ps). Such
      dynamic planarization of the molecular backbone is evident from the time
      dependent increase in the overall emission intensity and red-shift in the peak
      emission energy that can be observed for wormlike flexible porphyrin octamers but
      not for torsionally rigidified cyclic or double-strand octamer complexes. These
      results therefore indicate that, following excitation, the initially highly
      delocalized excited-state wave function first contracts and then expands again
      along the conjugated backbone in accordance with the time periods for the
      vibrational modes coupled to the electronic transition.

PMID- 18613664
TI  - Distinct reactivity of Pd(OTs)2: the intermolecular Pd(II)-catalyzed 1,2
      carboamination of dienes.
AB  - A Pd-catalyzed intermolecular 1,2-carboamination route to indolines from N-aryl
      ureas and 1,3-dienes that proceeds under mild conditions in relatively nonacidic
      media, is presented. The in situ generation, or preformation, of a palladium
      tosylate emerges as a key parameter in gaining the requisite reactivity for the C
      H insertion/carbopalladation/nucleophilic displacement process.

PMID- 18613667
TI  - Autonomous DNA computing machine based on photochemical gate transition.
AB  - We report the construction of a one-pot autonomous DNA computing machine based on
      photochemical gate transition (photocleavage, hybridization, and photoligation),
      and we performed binary digit additions using this machine. In our method, both
      photochemical DNA manipulations previously reported, photoligation via 5
      carboxyvinyldeoxyuridene (cvU) containing ODN and photocleavage via carbazole
      modified ODN, were employed. The binary digit additions were autonomously carried
      out by one-time irradiation at 366 nm in the single test tube. The fluorescence
      readout by the DNA chip was in good agreement with the correct answer of binary
      digit additions. We believe that this system is easily applicable to correlation
      analysis between SNPs as well as other binary digit processing, such as
      subtraction.

PMID- 18613668
TI  - Intra- and intermolecular NMR studies on the activation of arylcyclometallated
      hafnium pyridyl-amido olefin polymerization precatalysts.
AB  - Pyridyl-amido catalysts have emerged recently with great promise for olefin
      polymerization. Insights into the activation chemistry are presented in an
      initial attempt to understand the polymerization mechanisms of these important
      catalysts. The activation of C1-symmetric arylcyclometallated hafnium pyridyl
      amido precatalysts, denoted Me2Hf{N(-),N,C(-)} (1, aryl = naphthyl; 2, aryl =
      phenyl), with both Lewis (B(C6F5)3 and [CPh3][B(C6F5)4]) and Bronsted
      ([HNR3][B(C6F5)4]) acids is investigated. Reactions of 1 with B(C6F5)3 lead to
      abstraction of a methyl group and formation of a single inner-sphere
      diastereoisomeric ion pair [MeHf{N(-),N,C(-)}][MeB(C6F5)3] (3). A 1:1 mixture of
      the two possible outer-sphere diastereoisomeric ion pairs [MeHf{N(-),N,C(
      )}][B(C6F5)4] (4) is obtained when [CPh3][B(C6F5)4] is used. [HNR3][B(C6F5)4]
      selectively protonates the aryl arm of the tridentate ligand in both precatalysts
      1 and 2. A remarkably stable [Me2Hf{N(-),N,C2}][B(C6F5)4] (5) outer-sphere ion
      pair is formed when the naphthyl substituent is present. The stability is
      attributed to a hafnium/eta(2)-naphthyl interaction and the release of an
      eclipsing H-H interaction between naphthyl and pyridine moieties, as evidenced
      through extensive NMR studies, X-ray single crystal investigation and DFT
      calculations. When the aryl substituent is phenyl, [Me2Hf{N(-),N,C2}][B(C6F5)4]
      (10) is originally obtained from protonation of 2, but this species rapidly
      undergoes remetalation, methane evolution, and amine coordination, giving a
      diastereomeric mixture of [MeHf{N(-),N,C(-)}NR3][B(C6F5)4] (11). This species
      transforms over time into the trianionic-ligated [Hf{N(-),C(-),N,C(
      )}NR3][B(C6F5)4] (12) through activation of a C-H bond of an amido-isopropyl
      group. In contrast, ion pair 5 does not spontaneously undergo remetalation of the
      naphthyl moiety; it reacts with NMe2Ph leading to [MeHf{N(
      ),N}NMe2C6H4][B(C6F5)4] (7) through ortho-metalation of the aniline. Ion pair 7
      successively undergoes a complex transformation ultimately leading to [Hf{N(-),C(
      ),N,C(-)}NMe2Ph][B(C6F5)4] (8), strictly analogous to 12. The reaction of 5 with
      aliphatic amines leads to the formation of a single diastereomeric ion pair
      [MeHf{N(-),N,C(-)}NR3][B(C6F5)4] (9). These differences in activation chemistry
      are manifested in the polymerization characteristics of these different
      precatalyst/cocatalyst combinations. Relatively long induction times are observed
      for propene polymerizations with the naphthyl precatalyst 1 activated with
      [HNMe3Ph][B(C6F5)4]. However, no induction time is present when 1 is activated
      with Lewis acids. Similarly, precatalyst 2 shows no induction period with either
      Lewis or Bronsted acids. Correlation of the solution behavior of these ion pairs
      and the polymerization characteristics of these various species provides a basis
      for an initial picture of the polymerization mechanism of these important
      catalyst systems.

PMID- 18613669
TI  - Theory of 1,3-dipolar cycloadditions: distortion/interaction and frontier
      molecular orbital models.
AB  - Quantum chemical calculations of activation barriers and reaction energies for
      1,3-dipolar cycloadditions by the high-accuracy CBS-QB3 method reveal previously
      unrecognized quantitative trends in activation barriers. The
      distortion/interaction model of reactivity explains why (1) there is a monotonic
      decrease of approximately 6 kcal/mol in the activation energy along the series
      oxides, imine, and ylide for the diazonium, nitrilium, and azomethine betaine
      classes of 1,3-dipoles; (2) nitrilium and azomethine betaines with the same trio
      of atoms have almost identical cycloaddition barrier heights; (3) barrier heights
      for the cycloadditions of a given 1,3-dipole with ethylene and acetylene have the
      same activation energies (mean absolute deviation of 0.6 kcal/mol) in spite of
      very different reaction thermodynamics (Delta DeltaH(rxn) range = 14-43 kcal/mol)
      and frontier molecular orbital (FMO) energy gaps. The energy to distort the 1,3
      dipole and dipolarophile to the transition state geometry, rather than FMO
      interactions or reaction thermodynamics, controls reactivity for cycloadditions
      of 1,3-dipoles with alkenes or alkynes. A distortion/interaction energy analysis
      was also carried out on the transition states for the cycloadditions of diazonium
      dipoles with a set of substituted alkenes (CH2CHX, X = OMe, Me, CO 2Me, Cl, CN)
      and reveals that FMO interaction energies between the 1,3-dipole and the
      dipolarophile differentiate reactivity when transition state distortion energies
      are nearly constant.

PMID- 18613670
TI  - Thermodynamics and mechanism of the deamidation of sodium-bound asparagine.
AB  - The deamidation of asparagine (Asn) residues is the most common type of
      spontaneous post-translational protein modification and plays a vital role in
      inflammation, protein transformation, apoptosis, aging, and a number of
      degenerative diseases. Here we present a full molecular description of asparagine
      deamidation in the Na(+)(Asn) complex by studying its collision-induced
      dissociation (CID) with Xe using a guided ion beam tandem mass spectrometer
      (GIBMS). Advanced methods for analysis of the energy-dependent CID cross section,
      considering both competing and sequential processes, provide the 0 K barrier for
      deamidation after accounting for unimolecular decay rates, internal energy of
      reactant ions, and multiple ion-neutral collisions. Relaxed potential energy
      surface scans performed at the B3LYP/6-31G(d) level identify the transition state
      (TS) and intermediate reaction species for Na(+)(Asn) deamidation, structures
      that are further optimized at the B3LYP/6-311+G(d,p) level. Single-point energies
      of the key optimized structures are calculated at MP2(full), B3LYP, and B3P86
      levels using a 6-311+G(2d,2p) basis set. This coordinated application of both
      experimental work and quantum chemical calculations allows for a complete
      characterization of the elementary steps of this reaction and identification of
      the rate-limiting elementary step of Asn deamidation. The latter is measured to
      require 1.61 +/- 0.08 eV and involves formation of a cyclic succinic ring
      structure.

PMID- 18613671
TI  - Construction of aryliridium-salen complexes: enantio- and cis-selective
      cyclopropanation of conjugated and nonconjugated olefins.
AB  - Two stable and optically active iridium-salen complexes were synthesized by
      introducing a tolyl or phenyl ligand at the apical position, respectively, via
      the S(E)Ar mechanism, and they were found to be efficient catalysts for cis
      selective asymmetric cyclopropanation. The scope of the cyclopropanation was
      wide, and the reactions of not only conjugated mono-, di-, and trisubstituted
      olefins but also nonconjugated terminal olefins proceeded with high enantio- and
      cis-selectivity, even in the presence of a functional group such as an ether or
      ester. The utility of this cyclopropanation was demonstrated by a short step
      synthesis of 8-[(1R,2S)-2-hexylcyclopropyl]octanoate, isolated from Escherichia
      coli B-ATCC 11303, using the reaction as the key step.

PMID- 18613672
TI  - Ti(IV)-centered dynamic interconversion between Pd(II), Ti(IV)-containing ring
      and cage molecules.
AB  - Heteronuclear, supramolecular ring and cage complexes have been constructed from
      a pyridyl catechol ligand, TiO(acac)2, and PdCl2(CH3CN)2. These two complexes are
      quantitatively interconvertible, in which Ti4+-centered coordination changes take
      place between a well-known Ti(catecholato)3 and a newly established
      TiH(catecholato)2(acetylacetonato) structures. The Ti4+-centered structural
      changes arise from the changes in the component fraction and basicity condition.

PMID- 18613673
TI  - Microwave activation of enzymatic catalysis.
AB  - Microwave irradiation can be used to regulate biocatalysis. Herein, the
      utilization of hyperthermophilic enzymes in a microwave reactor is reported.
      While these enzymes are inactive at low temperatures, they can be activated with
      microwave irradiation. To the best of our knowledge, this is the first
      illustration of a specific microwave effect in enzymatic catalysis.

PMID- 18613674
TI  - Extended metal-atom chains with an inert second row transition metal: [Ru5(mu5
      tpda)4X2] (tpda2- = tripyridyldiamido dianion, X = Cl and NCS).
AB  - EMACs (extended metal-atom chains) offer a unique platform for the exploration of
      metal-metal interactions. There has been significant advances on the synthesis of
      EMACs, such as lengthening the chains up to 11 metal atoms thus far, integrating
      naphthyridine moieties for tuning the charge carried at metal centers, and
      manipulation of metal-metal interactions. However, the metal centers in EMACs
      hitherto are limited to first row transition metals which are more labile than
      those relatively inert ones with electrons filled in the 4d and 5d shells. In
      this Communication, the synthesis, crystallographic, magnetic, and electrical
      conducting studies of [Ru5(mu5-tpda)4Cl2] and [Ru5(mu5-tpda)4(NCS)2], the first
      pentanuclear EMACs of second-row transition metal, are reported.

PMID- 18613675
TI  - Selective disruption of early/recycling endosomes: release of disulfide-linked
      cargo mediated by a N-alkyl-3beta-cholesterylamine-capped peptide.
AB  - The use of endocytic uptake pathways to deliver poorly permeable molecules into
      mammalian cells is often plagued by entrapment and degradation of material in
      late endosomes and lysosomes. As a strategy to prevent the exposure of cargo to
      these highly hydrolytic membrane-sealed compartments, we synthesized derivatives
      of the membrane anchor N-alkyl-3beta-cholesterylamine that selectively target
      linked compounds to less hydrolytic early/recycling endosomes. By targeting a pH
      dependent membrane-lytic dodecapeptide and a disulfide-linked fluorophore to
      these compartments in Chinese hamster ovary cells or Jurkat lymphocytes,
      membranes of early/recycling endosomes were selectively disrupted, resulting in
      cleavage of the disulfide and escape of the fluorophore into the cytosol and
      nucleus with low toxicity. The ability of appropriately designed N-alkyl-3beta
      cholesterylamines to deliver cargo into and release disulfide-linked cargo from
      relatively nonhydrolytic early/recycling endosomes may be useful for the delivery
      of a variety of sensitive molecules into living mammalian cells.

PMID- 18613676
TI  - Reversible mechanochromic luminescence of [(C6F5Au)2(mu-1,4-diisocyanobenzene)].
AB  - Reversible mechanochromic luminescence of [(C6F5Au)2(mu-1,4-diisocyanobenzene)]
      is reported. Grinding of the complex induced a photoluminescent color change,
      which was restored by exposure to a solvent. This cycle was repeated 20 times
      with no color degradation in the emissions. Their optical properties, X-ray
      crystallographic analysis, IR, and XRD measurements strongly suggested that the
      change in the molecular arrangement is responsible for this mechanochromic
      property. Intermolecular aurophilic bondings presumably play a key role in the
      altered emission.

PMID- 18613677
TI  - Self-assembly of perylenediimide and naphthalenediimide nanostructures on glass
      substrates through deposition from the gas phase.
AB  - Micrometer-long nanobelt and nanowires from deposition of perylenediimide (PTCDI)
      and naphthalenediimide (NPDI) in glass substrates from the gas phase were
      demonstrated. The electron diffraction pattern of PTCDI shows that the PTCDI
      molecules are oriented with their long axis perpendicular to the belt and the pi
      pi stacking direction parallel to the belt. No crystal structure of the NPDI
      nanowires was observed. This is a new strategy to assemble organic molecules to
      nanostructures, typically for those having very low solubility in solvents. The
      approach would completely eliminate the effect of side chains.

PMID- 18613679
TI  - Zn modification of the reactivity of Pd(111) toward methanol and formaldehyde.
AB  - The adsorption and reaction of methanol and formaldehyde on two-dimensional PdZn
      alloys on a Pd(111) surface were studied as a function of the Zn content in the
      alloy in order to understand the role of Zn in Pd/ZnO catalysts for the steam
      reforming of methanol (SRM). Temperature programmed desorption (TPD) and high
      resolution electron energy loss spectroscopy (HREELS) data show that Zn atoms
      incorporated into the Pd(111) surface dramatically decrease the dehydrogenation
      activity and alter the preferred bonding sites for adsorbed CO, CH3O, and CH2O
      intermediates. The experimental results obtained in this study are consistent
      with previous theoretical studies of this system and provide new insight into how
      Zn alters the reactivity of Pd.

PMID- 18613678
TI  - NMR-assisted prediction of RNA secondary structure: identification of a probable
      pseudoknot in the coding region of an R2 retrotransposon.
AB  - As the rate of functional RNA sequence discovery escalates, high-throughput
      techniques for reliable structural determination are becoming crucial for
      revealing the essential features of these RNAs in a timely fashion. Computational
      predictions of RNA secondary structure quickly generate reasonable models but
      suffer from several approximations, including overly simplified models and
      incomplete knowledge of significant interactions. Similar problems limit the
      accuracy of predictions for other self-folding polymers, including DNA and
      peptide nucleic acid (PNA). The work presented here demonstrates that
      incorporating unassigned data from simple nuclear magnetic resonance (NMR)
      experiments into a dynamic folding algorithm greatly reduces the potential
      folding space of a given RNA and therefore increases the confidence and accuracy
      of modeling. This procedure has been packaged into an NMR-assisted prediction of
      secondary structure (NAPSS) algorithm that can produce pseudoknotted as well as
      non-pseudoknotted secondary structures. The method reveals a probable pseudoknot
      in the part of the coding region of the R2 retrotransposon from Bombyx mori that
      orchestrates second-strand DNA cleavage during insertion into the genome.

PMID- 18613681
TI  - Tracking the chemistry of unsaturated C3H3 groups adsorbed on a silver surface:
      propargyl-allenyl-acetylide triple bond migration, self-hydrogenation, and carbon
      carbon bond formation.
AB  - A diverse array of unsaturated C1 (methylene and methylidyne) and C2 (vinyl,
      vinylidene, ethylidene, and ethylidyne) bound to metal center(s) and surfaces has
      received much attention. In sharp contrast to the effort devoted to C1 and C2
      ligands, complexes or surfaces bearing C3 fragments have been less explored,
      especially the M-C3H3 systems, which include propargyl (M-CH2C[triple bond]CH),
      allenyl (M-CH=C=CH2), and acetylide (M-C[triple bond]CCH3) forms. To understand
      the bonding and reactivity of these C3 species appended to an extended metal
      structure, proprargyl bromide (Br-CH2C[triple bond]CH) was utilized as a
      precursor to generate C3H3 fragments on a Ag(111) surface under ultrahigh vacuum
      conditions. The molecular transformation process was explored by a combination of
      temperature-programmed desorption (TPD), reflection absorption infrared
      spectroscopy (RAIRS), and X-ray photoemission spectroscopy (XPS) techniques. In
      addition, density functional theory (DFT) calculations were conducted to obtain
      the optimized geometries and energies for the various surface intermediates. The
      computed IR spectra facilitated the vibrational mode assignments. TPD spectra
      show that C3H3(ad) self-hydrogenates to C3H4 around 300 and 475 K, respectively.
      In addition to hydrogenation, a C-C coupling product C6H6 (2,4-hexadiyne) is also
      unveiled as part of the desorption feature at 475 K. Identification of the
      possible C3H4 isomers (propyne and/or allene) was equivocal, but it was
      circumvented by using an alpha,alpha-dimethyl-substituted propargylic species-
      (CH3)2(alpha)C-C[triple bond]CH, which results in hydrogenation products, alkynic
      (CH3)2CH-C[triple bond]CH and allenic (CH3)2C=C=CH2, distinguishable by the mass
      spectrometry. The substitution experiments clarify that in the normal case the
      convoluted TPD feature around 300 K, in fact, consists of both allene at 260 K
      and propyne at 310 K, while the last hydrogenation product at 475 K is solely
      propyne. The RAIR spectroscopy demonstrates that at 200 K C3H3(ad) on Ag(111)
      readily adopts the allenyl formalism involving concerted CBr bond scission and
      [1,3]-sigmatropic migration (i.e., Br-*CH2C[triple bond]CH --> *CH2=C=CH-Ag), in
      which the sigma bond moves to a new metal location across the pi-periphery.
      Single hydrogen incorporation to the alpha-carbon of the surface allenyl
      rationalizes the allene formation at 260 K. When the surface is heated to the
      range of 250-300 K, both RAIR and XP spectra reveal drastic changes, indicative
      of a new species whose spectral characteristics could be duplicated by separate
      measurements from 1-propyn-1-yl iodide (CH3-C[triple bond]C-I) being a direct
      source for the surface methylacetylide (CH3-C[triple bond]C-Ag). It is thus
      suggested that allenyl is further reorganized to render acetylide presumably via
      [1,3]-hydrogen shift (i.e., *CH2=C=CH-Ag --> *CH3=C[triple bond]C-Ag). The
      presence of this third Ag-C3H3 isomeric form demonstrates an unprecedented
      propargyl-allenyl-acetylide multiple rearrangements on a metal surface. Migration
      of the triple bond from the remote terminal position into the chain, through the
      stage of allenic structure, is driven by thermodynamic stabilities, supported by
      the DFT total energy calculations. Consequently, the evolutions of propyne at 310
      and 475 K, as well as 2,4-hexadiyne (bismethylacetylide), can all be reasoned
      out.

PMID- 18613682
TI  - (CrCl3)3@2[C4mim][OMe]-molecular cluster-type chromium(III) chloride stabilized
      in a salt matrix.
AB  - In [C4mim]2[CrCl3]3[OMe]2 molecular (CrCl3)3 units are embedded in a salt matrix
      of [C4mim][OMe]. This structural subunit can be viewed as a trapped molecular
      polymorph of CrCl3. Experimental and theoretical investigations indicate that, in
      contrast to bulk CrCl3, metal-metal bonds are formed at low temperatures.

PMID- 18613684
TI  - Reversible emergence of a self-assembled layered structure from three-dimensional
      isotropic ionic crystal of a cluster compound (4-HNC5H4OH)2Mo6Cl14 driven by
      absorption of water and alcohols.
AB  - The compound comprising nanometer scale cluster molecules showed unusual
      reversible structural transformation between an isotropic ionic crystal and a
      layered structure of which the interlayer spaces are filled with the absorbed
      molecules.

PMID- 18613683
TI  - Molecular dynamics simulation of the HOONO decomposition and the HO*/NO2* caged
      radical pair in water.
AB  - The decomposition of HOONO in water gives nitrate and a reactive oxidant whose
      identity has been debated. This oxidant has been argued to be a hydroxyl radical,
      but reported yields of hydroxyl-radical-trapped products range from only 0% to
      40% in different experiments. Other oxidants, including the metastable HOONO*,
      have been proposed as intermediates. CPMD metadynamics simulations reported here
      show the mechanism of HOONO decomposition in water and the nature of the caged
      radical pair.

PMID- 18613685
TI  - Synthesis, crystallization mechanism, and catalytic properties of titanium-rich
      TS-1 free of extraframework titanium species.
AB  - A new route to the synthesis of TS-1 has been developed using (NH4)2CO3 as a
      crystallization-mediating agent. In this way, the framework Ti content can be
      significantly increased without forming extraframework Ti species. The prepared
      catalyst had a Si/Ti ratio as low as 34 in contrast to the ratio of 58 achieved
      with the methods A and B established by the Enichem group (Clerici, M. G.;
      Bellussi, G.; Romano, U. J. Catal. 1991, 129, 159) and Thangaraj and Sivasanker
      (Thangaraj, A.; Sivasanker, S. J. Chem. Soc., Chem. Commun. 1992, 123),
      respectively. The material contained less defect sites than the samples
      synthesized by the other two methods. As a result, it showed much higher activity
      for the oxidation of various organic substrates, such as linear alkanes/alkenes
      and alcohols, styrene, and benzene. The crystallization mechanism of TS-1 in the
      presence of (NH4)2CO3 was studied by following the whole crystallization process
      with X-ray diffraction (XRD), field emission scanning electron microscopy (FE
      SEM), thermogravimetry/differential thermal analysis (TG/DTA), inductively
      coupled plasma atomic emission spectrometry (ICP), Fourier transform infrared
      spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), diffuse reflectance
      UV-vis spectroscopy, and (29)Si MAS (magic-angle spinning) NMR spectroscopy
      techniques. It was shown that the presence of (NH4)2CO3 not only drastically
      lowered down pH, slowing down the crystallization process and making the
      incorporation of Ti into the framework match well with nucleation and crystal
      growth, but also modified the crystallization mechanism. It seems that the solid
      phase transformation mechanism predominated in the crystallization process
      initiated by dissociation, reorganization, and recoalescence of the solidified
      gel although a small amount of nongelatinated Ti shifted to the solid during the
      crystal growth period. In contrast, a typical homogeneous nucleation mechanism
      occurred in the method A system. Thus, although in the method A system most of Ti
      cations was inserted into the lattice after the crystallization was nearly
      completed, the inclusion of Ti started at the earlier nucleation period in the
      presence of (NH4)2CO3. This is favorable for the incorporation of Ti into the
      framework, resulting in a more homogeneous distribution of Ti in the framework.
      Oxidation of 1-hexene and 2-hexanol over the samples collected during the whole
      crystallization process indicated that condensation of Ti-OH and Si-OH proceeded
      even after the crystallization was completed. This resulted in an increase in
      hydrophobicity and an overall improvement in microscopic character of Ti species
      and consequently a great increase in the catalytic activity with further progress
      of crystallization.

PMID- 18613686
TI  - Bis-sulfonyl ethylene as masked acetylene equivalent in catalytic asymmetric [3 +
      2] cycloaddition of azomethine ylides.
AB  - Enantioenriched 3-pyrrolines have been synthesized by highly enantioselective
      Fesulphos-Cu-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with trans
      1,2-bisphenylsulfonyl ethylene, followed by reductive sulfonyl elimination. High
      levels of reactivity, exoselectivity, and enantioselectivity have been
      accomplished for a variety of substituted azomethine ylides. This cycloaddition
      desulfonylation strategy has been applied as a key step in the enantioselective
      synthesis of a biologically active C-azanucleoside.

PMID- 18613687
TI  - Isothermal assembly of DNA origami structures using denaturing agents.
AB  - DNA origami is one of the most promising recent developments in DNA self
      assembly. It allows for the construction of arbitrary nanoscale patterns and
      objects by folding a long viral scaffold strand using a large number of short
      "staple" strands. Assembly is usually accomplished by thermal annealing of the
      DNA molecules in buffer solution. We here demonstrate that both 2D and 3D origami
      structures can be assembled isothermally by annealing the DNA strands in
      denaturing buffer, followed by a controlled reduction of denaturant
      concentration. This opens up origami assembly for the integration of temperature
      sensitive components.

PMID- 18613688
TI  - Electrochemically controlled hydrogen bonding. Electrolyte effects in an
      oxidation-based arylurea-amide system.
AB  - Oxidation of a dimethylaminophenyl-substituted urea leads to a > 2000-fold
      increase in binding strength between the urea and a diamide guest in 0.1 M
      NBu4B(C6F5)4/CH2Cl2. The strength of this interaction is obscured when NBu4ClO4
      or NBu4PF6 is used as the electrolyte due to competition between the neutral
      guest and the electrolyte anion for H-bonding to the urea cation.

PMID- 18613689
TI  - Determination and isolation of a thioesterase from passion fruit (Passiflora
      edulis Sims) that hydrolyzes volatile thioesters.
AB  - Volatile organosulfur compounds (VOSCs) are high impact aroma chemicals
      characteristic of tropical fruits which are active as both free thiols and the
      respective thioesters. Using a simple and sensitive colorimetric enzyme assay, a
      thioesterase activity toward VOSCs has been identified in ripening purple passion
      fruit ( Passiflora edulis Sims). The assay was based on determining the release
      of free thiols from 2-methyl-3-furanthiol acetate using Ellman's reagent. The
      major thioesterase in the fruit was found to be a wall-bound protein in the
      mesocarp. The extracted enzyme activity was purified 150-fold and shown to be
      associated with a 43 kDa monomeric serine hydrolase which was selectively labeled
      with a fluorophosphonate suicide probe. MS-MS sequencing identified the
      thioesterase as a class 13 glycoside hydrolase, most similar to pectin
      acetylesterase, an enzyme involved in cell wall modifications in the peel of a
      number of fruit. Our results suggest that cell wall hydrolases in tropical fruit
      may have additional useful roles in biotransforming VOSCs.

PMID- 18613690
TI  - Indium-mediated regio- and chemoselective synthesis of alpha-hydroxyalkyl allenic
      esters and gold-catalyzed cyclizations to ethyl 2-naphthoate derivatives.
AB  - The regio- and chemoselective synthetic method of functionalized alpha
      hydroxyalkyl allenic esters was developed from the reactions of various aldehydes
      with organoindium reagent generated in situ from indium and ethyl 4
      bromobutynoate. The alpha-hydroxyalkyl allenic esters possessing electron
      donating groups were cyclized to ethyl 2-naphthoate derivatives through
      intramolecular C-alkylation catalyzed by gold salts.

PMID- 18613691
TI  - Copper-mediated C-H bond arylation of arenes with arylboronic acids.
AB  - A new copper-mediated cross-coupling of arenes and arylboronic acids is
      described. Under the influence of Cu(OCOCF 3) 2, the C-H bond arylation of
      electron-rich arenes with arylboronic acids takes place to afford a range of
      biaryls in good yields. The reaction is selective for cross-coupling; no
      homocoupling product arising from arenes or arylboronic acids is detected.
      Multiple C-H bond arylation is possible with indoles and pyrroles furnishing
      interesting extended pi-systems.

PMID- 18613692
TI  - A highly stereoselective synthesis of chiral alpha-amino-beta-lactams via the
      Kinugasa reaction employing ynamides.
AB  - A highly stereoselective synthesis of chiral alpha-amino-beta-lactam through an
      ynamide-Kinugasa reaction is described. In addition, a mechanistic model is
      illustrated here to rationalize the observed diastereoselectivity, which depends
      on both the initial [3 + 2] cycloaddition step and the subsequent protonation for
      which both are highly selective.

PMID- 18613693
TI  - Pd-catalyzed sequential reactions via allene intermediate for the synthesis of
      polycyclic frameworks containing 2,3-dihydrofuran units.
AB  - A stepwise process involving Sonogashira coupling, propargyl allenyl
      isomerization, and consecutive [4 + 2] cyclization has been realized, leading to
      an efficient synthesis of polycyclic compounds containing a 2,3-dihydrofuran
      unit. Most attractive for synthetic interest is the finding that up to four
      stereogenic centers could be generated in one step with high stereoselectivity.

PMID- 18613694
TI  - 2-Arylhydroxytyrosol derivatives via Suzuki-Miyaura cross-coupling.
AB  - 2-Arylhydroxytyrosol derivatives, a new class of hydroxytyrosol derivatives, have
      been prepared in high to excellent yields from the corresponding 2-chloro
      precursors via Suzuki-Miyaura cross-coupling with arylboronic acids containing
      electron-donating, electron-withdrawing, as well as ortho substituents. A
      remarkable halide effect has been observed. 2-Iodo- and 2-bromohydroxytyrosol
      derivatives have been found to be ineffective cross-coupling partners in many
      cases. The acetonide and carbonate protecting groups can be readily removed.

PMID- 18613695
TI  - A new entry to carbocyclic nucleosides: oxidative coupling reaction of
      cycloalkenylsilanes with a nucleobase mediated by hypervalent iodine reagent.
AB  - A novel method for synthesizing carbocyclic nucleosides was developed. The new
      synthesis includes a direct coupling reaction of cycloalkenylsilanes with a
      silylated nucleobase catalyzed by a hypervalent iodine reagent. By applying the
      method, a novel carbocyclic cytidine derivative having
      bis(hydroxymethyl)cyclohexene as a pseudosugar moiety, designed as a potential
      anti-HIV agent, was successfully synthesized.

PMID- 18613696
TI  - Bidirectional switching of near IR emitting boradiazaindacene fluorophores.
AB  - Two novel distyryl-boradiazaindacene dyes with dimethylaminostyryl and
      pyridylethenyl substituents display opposite spectral shifts on protonation with
      TFA in organic solvents. This bidirectional switching of the dyes can be shown to
      be directly related to ICT donor and acceptor characteristics of the substituents
      attached to the BODIPY core. The observed spectral response of these dyes could
      be very useful in the design of novel NIR fluorescent ratiometric probes for pH.

PMID- 18613697
TI  - Enhanced stereoselectivity in photoelectrocyclization of tropolone ethers via
      confinement in chiral inductor-modified lyotropic liquid crystals.
AB  - Photochemistry of tropolone methyl ether ( 1) and optically pure ( S)-tropolone-2
      methylbutyl ether ( 4) has been examined in lyotropic liquid crystals (LCs) in
      the presence of a chiral inductor. LCs significantly enhance the influence of
      chiral inductors during the photoelectrocyclization of the tropolone ethers.
      Chiral inductors that lead to 1:1 mixtures of enantiomers or diastereomers in
      solution give products in up to 40% enantiomeric excess for 1 and 35%
      diastereomeric excess for 4 in LCs.

PMID- 18613698
TI  - Terminal aziridines by alpha-deprotonation/electrophile trapping of N-protected
      aziridine.
AB  - N-tert-Butylsulfonyl and N-tert-butylsulfinyl aziridine undergo alpha
      lithiation/electrophile trapping providing a new entry to terminal aziridines.
      With N-tert-butylsulfinyl aziridine complete asymmetric induction is observed
      alpha to nitrogen.

PMID- 18613700
TI  - Stripping analysis of nanomolar perchlorate in drinking water with a voltammetric
      ion-selective electrode based on thin-layer liquid membrane.
AB  - A highly sensitive analytical method is required for the assessment of nanomolar
      perchlorate contamination in drinking water as an emerging environmental problem.
      We developed the novel approach based on a voltammetric ion-selective electrode
      to enable the electrochemical detection of "redox-inactive" perchlorate at a
      nanomolar level without its electrolysis. The perchlorate-selective electrode is
      based on the submicrometer-thick plasticized poly(vinyl chloride) membrane spin
      coated on the poly(3-octylthiophene)-modified gold electrode. The liquid membrane
      serves as the first thin-layer cell for ion-transfer stripping voltammetry to
      give low detection limits of 0.2-0.5 nM perchlorate in deionized water,
      commercial bottled water, and tap water under a rotating electrode configuration.
      The detection limits are not only much lower than the action limit (approximately
      246 nM) set by the U.S. Environmental Protection Agency but also are comparable
      to the detection limits of the most sensitive analytical methods for detecting
      perchlorate, that is, ion chromatography coupled with a suppressed conductivity
      detector (0.55 nM) or electrospray ionization mass spectrometry (0.20-0.25 nM).
      The mass transfer of perchlorate in the thin-layer liquid membrane and aqueous
      sample as well as its transfer at the interface between the two phases were
      studied experimentally and theoretically to achieve the low detection limits. The
      advantages of ion-transfer stripping voltammetry with a thin-layer liquid
      membrane against traditional ion-selective potentiometry are demonstrated in
      terms of a detection limit, a response time, and selectivity.

PMID- 18613701
TI  - Microflow and crack formation patterns in drying sessile droplets of liposomes
      suspended in trehalose solutions.
AB  - Anhydrobiotic preservation potentially provides a means of long-term storage of
      mammalian cells in carbohydrate glasses under ambient conditions. During
      desiccation, sessile droplets of glass-forming carbohydrate solutions exhibit
      complex phenomena, including fluid flow, droplet deformation, and crack
      formation, all of which may alter the cell preservation efficacy. Cell-sized
      liposomes were employed as a model system to explore these phenomena in
      diffusively dried sessile droplets of trehalose solutions. Two factors were
      identified that strongly influenced the features of the desiccated droplets: the
      underlying surface and the liposomes themselves. In particular, the surface
      altered the droplet shape as well as the microflow pattern and, in turn, the
      moisture conditions encountered by the liposomes during desiccation. A ring
      deposit formed when the droplets were dried on polystyrene, as would be expected
      owing to the capillary flow that generally occurs in pinned droplets. In
      contrast, when dried on the more hydrophilic glass slide, the resulting droplets
      were thinner, and the liposomes accumulated near their centers, which was an
      unexpected result likely owing to the glass-forming nature of trehalose
      solutions. As might be anticipated given the variations in liposome distribution,
      the choice of surface also influenced crack formation upon continued drying. In
      addition to providing a preferential path for drying, such cracks are relevant
      because they could inflict mechanical damage on cells. The liposomes themselves
      had an even more profound effect on crack formation; indeed, whereas cracks were
      found in all droplets containing liposomes, in their absence few of the droplets
      cracked at all, regardless of the surface type. These complex drying dynamics
      merit further investigation in the development of anhydrobiotic preservation
      protocols, particularly with regard to the role therein of surface hydrophobicity
      and the cells themselves.

PMID- 18613702
TI  - Interaction of acetone with single wall carbon nanotubes at cryogenic
      temperatures: a combined temperature programmed desorption and theoretical study.
AB  - The interaction of acetone with single wall carbon nanotubes (SWCNTs) at low
      temperatures was studied by a combination of temperature programmed desorption
      (TPD) and dispersion-augmented density-functional-based tight binding (DFTB-D)
      theoretical simulations. On the basis of the results of the TPD study and
      theoretical simulations, the desorption peaks of acetone can be assigned to the
      following adsorption sites: (i) sites with energy of approximately 75 kJ mol (-1)
      ( T des approximately 300 K)endohedral sites of small diameter nanotubes (
      approximately 7.7 A); (ii) sites with energy 40-68 kJ mol (-1) ( T des
      approximately 240 K)acetone adsorption on accessible interstitial, groove sites,
      and endohedral sites of larger nanotubes ( approximately 14 A); (iii) sites with
      energy 25-42 kJ mol (-1) ( T des approximately 140 K)acetone adsorption on
      external walls of SWCNTs and multilayer adsorption. Oxidatively purified SWCNTs
      have limited access to endohedral sites due to the presence of oxygen
      functionalities. Oxygen functionalities can be removed by annealing to elevated
      temperature (900 K) opening access to endohedral sites of nanotubes. Nonpurified,
      as-received SWCNTs are characterized by limited access for acetone to endohedral
      sites even after annealing to elevated temperatures (900 K). Annealing of both
      purified and as-produced SWCNTs to high temperatures (1400 K) leads to reduction
      of access for acetone molecules to endohedral sites of small nanotubes, probably
      due to defect self-healing and cap formation at the ends of SWCNTs. No chemical
      interaction between acetone and SWCNTs was detected for low temperature
      adsorption experiments. Theoretical simulations of acetone adsorption on finite
      pristine SWCNTs of different diameters suggest a clear relationship of the
      adsorption energy with tube sidewall curvature. Adsorption of acetone is due to
      dispersion forces, with its C-O bond either parallel to the surface or O pointing
      away from it. No significant charge transfer or polarization was found. Carbon
      black was used to model amorphous carbonaceous impurities present in as-produced
      SWCNTs. Desorption of acetone from carbon black revealed two peaks at
      approximately 140 and approximately 180-230 K, similar to two acetone desorption
      peaks from SWCNTs. The characteristic feature of acetone desorption from SWCNTs
      was peak at approximately 300 K that was not observed for carbon black. Care
      should be taken when assigning TPD peaks for molecules desorbing from carbon
      nanotubes as amorphous carbon can interfere.

PMID- 18613703
TI  - Can t-Te nanowires really give blue-violet emission? Reply to comment on high
      quality luminescent tellurium nanowires of several nanometers in diameter and
      high aspect ratio synthesized by a poly(Vinyl Pyrrolidone)-assisted hydrothermal
      process.

PMID- 18613704
TI  - Processing of nanoporous Ag layers by potential-controlled displacement (PCD) of
      Cu.
AB  - A cementation-like process taking place under potential control and introduced in
      this work as a "potential-controlled displacement" (PCD) is developed as a new
      method for processing of nanoporous Ag structures with controlled roughness
      (porosity) length scales. Most of the development work is done in a deoxygenated
      electrolyte containing 1 x 10(-3) M AgClO(4 )+ 5 x 10(-2) M CuSO(4) + 1 x 10(-1)
      M HClO(4) using a copper rotating disk electrode at 50 rpm. At this electrolyte
      concentration, the Ag deposition is under diffusion limitations whereas the Cu
      dissolution displays a typical Butler-Volmer anodic behavior. Thus, a careful
      choice of the operational current density enables strict control of the ratio
      between the dissolving and depositing metals as ascertained independently by
      atomic absorption spectrometry (AAS). The roughness length scale of the resulting
      surfaces is controlled by a careful selection of the current density applied. The
      highest surface area and finest morphology is obtained when the atomic ratio of
      Ag deposition and Cu dissolution becomes 1:1. Preseeding of uniform Ag clusters
      on the Cu surface made by pulse plating of Ag along with complementary plating
      and stripping of Pb monolayer is found to yield finer length scale resulting in
      up to a 67% higher surface area. An electrochemical technique using as a
      reference value the charge of an underpotentially deposited Pb layer on a flat Ag
      surface is used for measuring the real surface area. Scanning electron microscopy
      (SEM) studies are conducted to examine and characterize the deposit morphology of
      Ag grown by PCD on Cu substrates.

PMID- 18613705
TI  - Emulsions stabilized by stimuli-sensitive poly(N-isopropylacrylamide)-co
      methacrylic acid polymers: microgels versus low molecular weight polymers.
AB  - Responsive polymer microgels can be employed for the preparation of stimuli
      sensitive emulsions. The microgels used in this study are based on cross-linked
      copolymers including N-isopropylacrylamide and methacrylic acid. We conducted the
      synthesis under acidic and basic conditions to investigate the effect of changes
      of comonomer solubility on the microgel's composition and ability to stabilize
      emulsions. The synthesis product was partially divided into two fractions by
      centrifugation. Raw product, collected supernatant, and purified microgel were
      characterized by means of light scattering, titration, as well as electrophoretic
      mobility. The ability of the three components to act as stabilizers was
      investigated by preparing the octanol/water emulsions and looking at their
      response to pH and temperature changes. The interfacial activity of the three
      components was characterized by means of the pendent drop technique. Furthermore,
      we investigated the response of the interface to dilatational stress using a
      pendant drop tensiometer equipped with an oscillating drop module. The results
      demonstrate that the pH during synthesis has a significant impact on the
      composition and thus the properties of the microgel and its ability to be
      utilized as a stimuli responsive stabilizer for emulsions. We conclude that
      microgels can be used as stimuli-sensitive stabilizers for emulsions, if the
      charges are incorporated in the microgel itself.

PMID- 18613707
TI  - Internal flow in polymer solution droplets deposited on a lyophobic surface
      during a receding process.
AB  - When a polymer solution droplet is deposited on a lyophobic surface, the contact
      line is moved back to some degree and subsequently pinned. An experimental setup
      is constructed to investigate not only the receding process but also an internal
      flow of polystyrene-acetophenone and -anisole solutions. As a result, the time
      variation of the evaporation rate per unit area during receding does not strongly
      depend on the initial solute concentration. The average solute concentration at
      the pinning of the contact line increases as the initial solute concentration
      increases. A convective circulation flow that is upward at the axis of symmetry
      is observed. This flow pattern is different from those of pure liquids such as
      water, acetone, benzene, and so forth, which have been previously reported.
      Furthermore, the observed flow is enhanced as the initial solute concentration
      increases, contrary to an increase in the fluid viscosity. To resolve these
      discrepancies, the mechanism of the flow is numerically investigated using a
      hemispherical droplet model considering the density and surface tension
      distributions. The numerical results demonstrate that the circulation flow that
      is experimentally observed is actually caused. It is also found that the solutal
      Rayleigh effect initially induces the internal flow, and subsequently the solutal
      Marangoni effect dominates the flow. Both effects are enhanced as the initial
      concentration increases because of the evaporative mass balance at the free
      surface.

PMID- 18613706
TI  - Determination of the surface area of Pd and nanometric Au aggregates supported on
      a micrometric solid support by thiol adsorption and GC-MS.
AB  - A new sensitive and specific method to measure gold and palladium surface areas
      using alkanethiol adsorption coupled with analysis by gas chromatography with
      mass spectrometry detection has been developed. The effectiveness of the method
      was tested with metallic samples having a known surface area. The results have
      also been compared with BET specific surface area measurements. The results
      obtained with both methods show a good correlation.

PMID- 18613708
TI  - Influence of binary surfactant mixtures on the rheology of associative polymer
      solutions.
AB  - Hydrophobically modified alkali-soluble emulsion polymers (HASE) are a class of
      comblike associative polymers that can impart high viscosities to aqueous
      solutions. The rheology of HASE solutions can be tuned by the addition of
      surfactants, such as nonylphenol ethoxylates (NP e), where e is the length of the
      hydrophilic (ethoxylate) chain. While previous studies have considered individual
      surfactants, our focus here is on binary surfactant mixtures. We find that
      equimolar NP4-NP12 mixtures significantly enhance the zero-shear viscosities of
      HASE solutions as compared to equivalent amounts of NP8, especially at high
      overall surfactant concentrations. Dynamic rheological measurements suggest that
      the higher viscosities are due to increases in the lifetime of hydrophobic
      junctions in the polymer-surfactant network. In contrast to the above results,
      equimolar NP4-NP8 mixtures are rheologically identical to equivalent solutions of
      NP6. The differences between the two sets of mixtures are further correlated with
      cloud point measurements and thereby with the overall hydrophilic-lipophilic
      balance (HLB) of the surfactant system.

PMID- 18613709
TI  - Double emulsion templated monodisperse phospholipid vesicles.
AB  - We present a novel approach for fabricating monodisperse phospholipid vesicles
      with high encapsulation efficiency using controlled double emulsions as
      templates. Glass-capillary microfluidics is used to generate monodisperse double
      emulsion templates. We show that the high uniformity in size and shape of the
      templates are maintained in the final phospholipid vesicles after a solvent
      removal step. Our simple and versatile technique is applicable to a wide range of
      phospholipids.

PMID- 18613710
TI  - Inside vs "Outside" photooxygenation reactions: singlet-oxygen-mediated surface
      passivation of polymer films.
AB  - Films of poly(acrylonitrile- co-2,3-dimethyl-1,3-butadiene) were exposed to
      singlet oxygen. The extent of polymer oxygenation was monitored for singlet
      oxygen generated (1) within the polymer film and (2) at the polymer surface in an
      aqueous medium. When singlet oxygen is generated within the film, oxygenation of
      the polymer is pronounced and extensive. When singlet oxygen is generated at the
      polymer surface, oxygenation reactions are limited to the surface. The data
      suggest that the initial oxygenation reactions at the film surface passivate the
      polymer against further reaction with singlet oxygen and, hence, also minimize
      the progressively detrimental effects of secondary reactions. These results
      indicate that one should exercise restraint when implicating singlet oxygen as a
      reactive species in some processes of polymer oxygenation.

PMID- 18613711
TI  - Microcalorimetric investigation of high-surface-area mesoporous titania samples
      for CO2 adsorption.
AB  - Mesoporous titania powders were synthesized using the triblock copolymer F127
      (PEO(106)PPO(70)PEO(106)) as a surfactant template. Two different procedures
      (ammonia and/or low-temperature treatment at 393 K) were successfully applied to
      stabilize the mesoporous structure, resulting in significantly increased surface
      areas and pore volumes with respect to those of the untreated titania powders.
      Three of these samples were chosen for further investigation by adsorption
      microcalorimetry. These samples are characterized by high surface areas (varying
      between 340 and 141 m (2) g (-1)) and a varying degree of crystallization
      (anatase phase). The samples were compared to nanosized anatase particles treated
      to 873 K. The adsorption microcalorimetry was carried out using nitrogen and
      carbon dioxide at 77 and 303 K, respectively, to gain complementary information
      about the surfaces. Nitrogen at 77 K showed, for the three samples, adsorption
      enthalpies at low coverage of similar values, approximately -19 to -22 kJ mol (
      1), indicating that the probe gas interacts with similar energetic surface sites.
      Two distinct energetic regions are observed, the first of which increases with
      increasing pretreatment temperature, which can be related to increased sample
      crystallinity. The adsorption of carbon dioxide at 303 K showed high adsorption
      enthalpies (up to approximately 65-80 kJ mol (-1)), highlighting strong
      interactions of the carbon dioxide with the titania surface at low pressures.
      Finally, the CO(2) adsorption properties of the titania samples (adsorbed amount
      and enthalpies of adsorption) are compared with those of other nanosized
      adsorbents. This comparison shows the potentiality of mesoporous titania powders
      for the adsorption of CO(2).

PMID- 18613712
TI  - Testing the accuracy of correlations for multicomponent mass transport of
      adsorbed gases in metal-organic frameworks: diffusion of H2/CH4 mixtures in
      CuBTC.
AB  - Mass transport of chemical mixtures in nanoporous materials is important in
      applications such as membrane separations, but measuring diffusion of mixtures
      experimentally is challenging. Methods that can predict multicomponent diffusion
      coefficients from single-component data can be extremely useful if these methods
      are known to be accurate. We present the first test of a method of this kind for
      molecules adsorbed in a metal-organic framework (MOF). Specifically, we examine
      the method proposed by Skoulidas, Sholl, and Krishna (SSK) ( Langmuir, 2003, 19,
      7977) by comparing predictions made with this method to molecular simulations of
      mixture transport of H 2/CH 4 mixtures in CuBTC. These calculations provide the
      first direct information on mixture transport of any species in a MOF. The
      predictions of the SSK approach are in good agreement with our direct simulations
      of binary diffusion, suggesting that this approach may be a powerful one for
      examining multicomponent diffusion in MOFs. We also use our molecular simulation
      data to test the ideal adsorbed solution theory method for predicting binary
      adsorption isotherms and a method for predicting mixture self-diffusion
      coefficients.

PMID- 18613713
TI  - Imaging mass spectrometry of intact proteins from alcohol-preserved tissue
      specimens: bypassing formalin fixation.
AB  - Imaging mass spectrometry is becoming a key technology for the investigation of
      the molecular content of biological tissue sections in direct correlation with
      the underlying histology. Much of our work has been done with fresh-frozen tissue
      sections that has undergone minimal protein degradation between the time a tissue
      biopsy is sampled and the time it is snap-frozen so that no preserving or fixing
      agents need to be added to the frozen biopsy. However, in many sampling
      environments, immediate flash freezing may not be possible and so we have
      explored the use of ethanol-preserved, paraffin-embedded tissue specimens for
      proteomic analyses. Solvent-only preserved tissue specimens provide long-term
      preservation at room temperature, generation of high quality histological
      sections and little if any chemical alteration of the proteins. Using mouse
      organs, several key steps involved in the tissue dehydration process have been
      investigated to assess the potential of such preserved specimens for profiling
      and imaging mass spectrometry investigations.

PMID- 18613714
TI  - Global relationship between the proteome and transcriptome of human skeletal
      muscle.
AB  - Skeletal muscle is one of the largest tissues in the human body. Changes in mRNA
      and protein abundance in this tissue are central to a large number of metabolic
      and other disorders, including, commonly, insulin resistance. Proteomic and
      microarray analyses are important approaches for gaining insight into the
      molecular and biochemical basis for normal and pathophysiological conditions.
      With the use of vastus lateralis muscle obtained from two groups of healthy,
      nonobese subjects, we performed a detailed comparison of the muscle proteome,
      obtained by HPLC-ESI-MS/MS, with the muscle transcriptome, obtained using
      oligonucleotide microarrays. HPLC-ESI-MS/MS analysis identified 507 unique
      proteins as present in four out of six subjects, while 5193 distinct transcripts
      were called present by oligonucleotide microarrays from four out of six subjects.
      The majority of the proteins identified by mass spectrometry also had their
      corresponding transcripts detected by microarray analysis, although 73 proteins
      were only identified in the proteomic analysis. Reflecting the high abundance of
      mitochondria in skeletal muscle, 30% of proteins detected were attributed to the
      mitochondrion, as compared to only 9% of transcripts. On the basis of Gene
      Ontology annotations, proteins assigned to mitochondrial inner membrane,
      mitochondrial envelope, structural molecule activity, electron transport, as well
      as generation of precursor metabolites and energy, had more corresponding
      transcripts detected than would be expected by chance. On the contrary, proteins
      assigned to Golgi apparatus, extracellular region, lyase activity, kinase
      activity, and protein modification process had fewer corresponding transcripts
      detected than would be expected by chance. In conclusion, these results provide
      the first global comparison of the human skeletal muscle proteome and
      transcriptome to date. These data show that a combination of proteomic and
      transcriptic analyses will provide data that can be used to test hypotheses
      regarding the pathogenesis of muscle disorders as well as to generate
      observational data that can be used to form novel hypotheses.

PMID- 18613716
TI  - Identification of reactive cysteines in a protein using arsenic labeling and
      collision-induced dissociation tandem mass spectrometry.
AB  - Trivalent arsenicals have high affinity for thiols (such as free cysteines) in
      proteins. We describe here the use of this property to develop a collision
      induced dissociation (CID) tandem mass spectrometry (MS/MS) technique for the
      identification of reactive cysteines in proteins. A trivalent arsenic species,
      dimethylarsinous acid (DMA (III)), with a residue mass (103.9607) and mass defect
      distinct from the normal 20 amino acids, was used to selectively label reactive
      cysteine residues in proteins. The CID fragment ions of the arsenic-labeled
      sequences shifted away from the more abundant normal fragments that would
      otherwise overlap with the ions of interest. Along with the internal and immonium
      ions, the arsenic-labeled fragment ions served as MS/MS signatures for
      identification of the binding sites and for assessment of the relative reactivity
      of individual cysteine residues in a protein. Using this method, we have
      identified two highly reactive binding sites in rat hemoglobin (Hb): Cys-13alpha
      and Cys-125beta. Cys-13alpha was bound to DMA (III) in the Hb of rats fed with
      arsenic, and this binding was responsible for arsenic accumulation in rat blood,
      while Cys-125beta was found to bind to glutathione in rat blood. This study
      revealed the relative reactivity of the cysteines in rat Hb in the following
      decreasing order: Cys-13alpha >> Cys-111alpha > Cys-104alpha and Cys-13alpha >>
      Cys-125beta > Cys-93beta. Arsenic-labeling is easy and fast for identification of
      active binding sites without enzymatic digestion and acid hydrolysis, and useful
      for characterization and identification of metal binding sites in other proteins.

PMID- 18613715
TI  - A proteomics grade electron transfer dissociation-enabled hybrid linear ion trap
      orbitrap mass spectrometer.
AB  - Here we detail the modification of a quadrupole linear ion trap-orbitrap hybrid
      (QLT-orbitrap) mass spectrometer to accommodate a negative chemical ionization
      (NCI) source. The NCI source is used to produce fluoranthene radical anions for
      imparting electron transfer dissociation (ETD). The anion beam is stable, robust,
      and intense so that a sufficient amount of reagents can be injected into the QLT
      in only 4-8 ms. Following ion/ion reaction in the QLT, ETD product ions are mass
      to-charge (m/z) analyzed in either the QLT (for speed and sensitivity) or the
      orbitrap (for mass resolution and accuracy). Here we describe the physical layout
      of this device, parametric optimization of anion transport, an evaluation of
      relevant ETD figures of merit, and the application of this instrument to protein
      sequence analysis. Described proteomic applications include complex peptide
      mixture analysis, post-translational modification (PTM) site identification,
      isotope-encoded quantitation, large peptide characterization, and intact protein
      analysis. From these experiments, we conclude the ETD-enabled orbitrap will
      provide the proteomic field with several new opportunities and represents an
      advance in protein sequence analysis technologies.

PMID- 18613717
TI  - Conjugation of complex polyubiquitin chains to WRNIP1.
AB  - Werner helicase interacting protein 1 (WRNIP1) is a ubiquitin-binding protein
      that undergoes extensive post-translational modification including
      ubiquitination, sumoylation, and phosphorylation. These post-translational
      modifications are expected to regulate the function of WRNIP1 in the DNA damage
      response. In this study, we use a denaturing tandem affinity purification
      technique along with mass spectrometry to show that, unlike most ubiquitin
      binding proteins, WRNIP1 is polyubiquitinated. WRNIP1 polyubiquitination is
      reminiscent of the well-characterized phenomenon of the coupled
      monoubiquitination of ubiquitin-binding proteins in that this polyubiquitination
      is dependent on the presence of an intact ubiquitin-binding domain. The
      polyubiquitin chains conjugated to WRNIP1 are linked through lysines 11, 48, and
      63. This study presents the first evidence for the conjugation of K11-K48-K63
      polyubiquitin chains to a specific substrate in vivo. Polyubiquitination is
      likely to regulate WRNIP1's function in the DNA damage response, as UV radiation
      induces the hyperubiquitination of WRNIP1. Polyubiquitination with noncanonical
      intraubiquitin linkages may represent a unique mode of regulation of UBZ domain
      containing proteins.

PMID- 18613718
TI  - Highly hydrothermally stable microporous silica membranes for hydrogen
      separation.
AB  - Fluorocarbon-modified silica membranes were deposited on gamma-Al2O3/alpha-Al2O3
      supports by the sol-gel technique for hydrogen separation. The hydrophobic
      property, pore structure, gas transport and separation performance, and
      hydrothermal stability of the modified membranes were investigated. It is
      observed that the water contact angle increases from 27.2+/-1.5 degrees for the
      pure silica membranes to 115.0+/-1.2 degrees for the modified ones with a
      (trifluoropropyl)triethoxysilane (TFPTES)/tetraethyl orthosilicate (TEOS) molar
      ratio of 0.6. The modified membranes preserve a microporous structure with a
      micropore volume of 0.14 cm3/g and a pore size of approximately 0.5 nm. A single
      gas permeation of H2 and CO2 through the modified membranes presents small
      positive apparent thermal activation energies, indicating a dominant microporous
      membrane transport. At 200 degrees C, a single H2 permeance of 3.1x10(-6) mol m(
      2) s(-1) Pa(-1) and a H2/CO2 permselectivity of 15.2 were obtained after proper
      correction for the support resistance and the contribution from the defects. In
      the gas mixture measurement, the H2 permeance and the H2/CO2 separation factor
      almost remain constant at 200 degrees C with a water vapor pressure of 1.2x10(4)
      Pa for at least 220 h, indicating that the modified membranes are hydrothermally
      stable, benefiting from the integrity of the microporous structure due to the
      fluorocarbon modification.

PMID- 18613719
TI  - Aggregation behavior of fluorocarbon and hydrocarbon cationic surfactant
      mixtures: a study of 1H NMR and 19F NMR.
AB  - The aggregation behavior and the interaction of four mixed systems for a cationic
      fluorocarbon surfactant, diethanolheptadecafluoro-2-undecanolmethylammonium
      chloride (DEFUMACl), mixing with cationic hydrocarbon surfactants,
      alkyltrimethylammonium chloride, CnTACl (n=12, 14, 16, and 18; where n=12 is
      DTACl, n=14 is TTACl, n=16 is CTACl, and n=18 is OTACl), were studied by 1H and
      19F NMR in more detail. The results of 19F NMR measurements strongly indicate
      that in the three mixed systems of DEFUMACl/DTACl, DEFUMACl/TTACl, and
      DEFUMACl/CTACl at different molar fractions of fluorocarbon surfactant
      (alphaF=(cDEFUMACl/cDEFUMACl+cCnTACl)), with an increase of the total
      concentration of fluorocarbon and hydrocarbon surfactants (cT=cF+cH), the mixed
      micelles at the first break point and the individual DEFUMACl micelles at the
      second break point form. However, three different types of micelles were
      determined in DEFUMACl/OTACl mixtures by 19F NMR measurements, OTACl-rich and
      DEFUMACl-rich mixed micelles and individual DEFUMACl micelles, respectively. The
      chemical shifts of proton Deltadelta (1H) for -CH3 in the mixed systems of
      DEFUMACl/CnTACl (n=12, 14, 16, and 18) have different variation trends from the
      19F NMR measurements. For the two systems of DEFUACl/DTACl and DEFUMACl/TTACl,
      the mixed micelles form at the first break point. At the second break point, for
      lower alpha F values the DTACl-rich and TTACl-rich mixed micelles form with a
      strong downfield shift and for higher alpha F values DEFUMACl-rich mixed micelles
      form with a strong upfield. For the other two systems of DEFUMACl/CTACl and
      DEFUMAC/OTACl, the chemical shifts of proton Deltadelta (1H) of -CH3 increase
      with an increase of the total concentration of DEFUMACl/CTACl or OTACl, and mixed
      CH- and CF-surfactant micelles form. At higher total concentration, the greater
      effect of fluorinated chains of DEFUMACl on CH-chains was obvious, resulting in
      the strong upfield chemical shifts. In cationic fluorocarbon and hydrocarbon
      surfactant mixtures, the different kinds of micelles observed by 19F and 1H NMR
      measurements could be caused by the increase in alkyl chain length of hydrocarbon
      surfactants with different critical micelle concentrations. Combining two
      theoretical models for mixing, for the four different chain-length hydrocarbon
      surfactants studied, one can conclude that the two components of mixtures
      interact with each other and form mixed micelles in two completely different ways
      according to their molecular properties and cmc values in a certain range of
      total concentrations. One is close to an ideal mixing case with the formation of
      one type of mixed micelles, such as the DEFUMACl/DTACl and DEFUMACl/TTACl
      systems. The other is a demixing case with the formation of two types of
      micelles, i.e., fluorocarbon-rich and hydrocarbon-rich mixed micelles, such as
      DEFUMACl/CTACl and DEFUMACl/OTACl systems. However, as the total concentrations
      of the mixed systems are high enough, the four systems tend to demix and to form
      individual micelles of corresponding components due to the initial respective
      interaction between fluorocarbon and hydrocarbon chains. That is to say, at high
      total concentration, the individual DEFUMACl micelles in all four systems could
      form. These results may be primarily directed toward acquiring an understanding
      of the mechanism of CF-CH mixtures in aqueous solution and secondarily directed
      toward providing more detailed information on nonideal mixing.

PMID- 18613720
TI  - Potential energy landscape of bis(fluorosulfonyl)amide.
AB  - The conformational landscape of the bis(fluorosulfonyl)amide, [FSI]-, anion was
      analyzed using data obtained from Raman spectroscopy, molecular dynamics (MD),
      and ab initio studies. The plotting of three-dimensional potential energy
      surfaces and the corresponding MD simulation conformer-population histograms show
      the existence of two stable isomers, C2 (trans) and C1 (cis) conformers, and
      confirm the nature of the anion as a flexible molecule capable of interconversion
      between conformers in the liquid state. In ionic liquids, the two [FSI]-
      conformers coexist in equilibrium, a result confirmed by the Raman data. The
      implications of the conformational behavior of the ion [FSI]- are discussed in
      terms of the solvation properties of the corresponding ionic liquids.

PMID- 18613722
TI  - Drifting periodic structures in a degenerate-planar bent-rod nematic liquid
      crystal beyond the dielectric inversion frequency.
AB  - We report on the electric-field-generated effects in the nematic phase of a twin
      mesogen formed of bent-core and calamitic units, aligned homeotropically in the
      initial ground state and examined beyond the dielectric inversion point. The bend
      Freedericksz (BF) state occurring at the primary bifurcation and containing a
      network of umbilics is metastable; we focus here on the degenerate planar (DP)
      configuration that establishes itself at the expense of the BF state in the
      course of an anchoring transition. In the DP regime, normal rolls, broad domains,
      and chevrons (both defect-mediated and defect-free types) form at various linear
      defect-sites, in different regions of the frequency-voltage plane. A significant
      novel aspect common to all these patterned states is the sustained propagative
      instability, which does not seem explicable on the basis of known driving
      mechanisms.

PMID- 18613721
TI  - Entropy and free energy of a mobile protein loop in explicit water.
AB  - Estimation of the energy from a given Boltzmann sample is straightforward since
      one just has to average the contribution of the individual configurations. On the
      other hand, calculation of the absolute entropy, S (hence the absolute free
      energy F) is difficult because it depends on the entire (unknown) ensemble. We
      have developed a new method called "the hypothetical scanning molecular dynamics"
      (HSMD) for calculating the absolute S from a given sample (generated by any
      simulation technique). In other words, S (like the energy) is "written" on the
      sample configurations, where HSMD provides a prescription of how to "read" it. In
      practice, each sample conformation, i, is reconstructed with transition
      probabilities, and their product leads to the probability of i, hence to the
      entropy. HSMD is an exact method where all interactions are considered, and the
      only approximation is due to insufficient sampling. In previous studies HSMD (and
      HS Monte CarloHSMC) has been extended systematically to systems of increasing
      complexity, where the most recent is the seven-residue mobile loop, 304-310 (Gly
      His-Gly-Ala-Gly-Gly-Ser) of the enzyme porcine pancreatic alpha-amylase modeled
      by the AMBER force field and AMBER with the implicit solvation GB/SA (paper I,
      Cheluvaraja, S.; Meirovitch, H. J. Chem. Theory Comput. 2008, 4, 192). In the
      present paper we make a step further and extend HSMD to the same loop capped with
      TIP3P explicit water at 300 K. As in paper I, we are mainly interested in entropy
      and free energy differences between the free and bound microstates of the loop,
      which are obtained from two separate MD samples of these microstates. The
      contribution of the loop to S and F is calculated by HSMD and that of water by a
      particular thermodynamic integration procedure. As expected, the free microstate
      is more stable than the bound microstate by a total free energy difference, Ffree
      Fbound=-4.8+/-1, as compared to -25.5 kcal/mol obtained with GB/SA. We find that
      relatively large systematic errors in the loop entropies, Sfree(loop) and
      Sbound(loop) are cancelled in their difference which is thus obtained efficiently
      and with high accuracy, i.e., with a statistical error of 0.1 kcal/mol. This
      cancellation, which has been observed in previous HSMD studies, is in accord with
      theoretical arguments given in paper I.

PMID- 18613723
TI  - Probing the effect of the binding site on the electrostatic behavior of a series
      of carotenoids reconstituted into the light-harvesting 1 complex from purple
      photosynthetic bacterium Rhodospirillum rubrum detected by stark spectroscopy.
AB  - Reconstitutions of the LH1 complexes from the purple photosynthetic bacterium
      Rhodospirillum rubrum S1 were performed with a range of carotenoid molecules
      having different numbers of C=C conjugated double bonds. Since, as we showed
      previously, some of the added carotenoids tended to aggregate and then to remain
      with the reconstituted LH1 complexes (Nakagawa, K.; Suzuki, S.; Fujii, R.;
      Gardiner, A.T.; Cogdell, R.J.; Nango, M.; Hashimoto, H. Photosynth. Res. 2008,
      95, 339-344), a further purification step using a sucrose density gradient
      centrifugation was introduced to improve purity of the final reconstituted
      sample. The measured absorption, fluorescence-excitation, and Stark spectra of
      the LH1 complex reconstituted with spirilloxanthin were identical with those
      obtained with the native, spirilloxanthin-containing, LH1 complex of Rs. rubrum
      S1. This shows that the electrostatic environments surrounding the carotenoid and
      bacteriochlorophyll a (BChl a) molecules in both of these LH1 complexes were
      essentially the same. In the LH1 complexes reconstituted with either rhodopin or
      spheroidene, however, the wavelength maximum at the BChl a Qy absorption band was
      slightly different to that of the native LH1 complexes. These differences in the
      transition energy of the BChl a Qy absorption band can be explained using the
      values of the nonlinear optical parameters of this absorption band, i.e., the
      polarizability change Tr(Deltaalpha) and the static dipole-moment change
      |Deltamu| upon photoexcitation, as determined using Stark spectroscopy. The local
      electric field around the BChl a in the native LH1 complex (ES) was determined to
      be approximately 3.0x10(6) V/cm. Furthermore, on the basis of the values of the
      nonlinear optical parameters of the carotenoids in the reconstituted LH1
      complexes, it is possible to suggest that the conformations of carotenoids,
      anhydrorhodovibrin and spheroidene, in the LH1 complex were similar to that of
      rhodopin glucoside in crystal structure of the LH2 complex from Rhodopseudomonas
      acidophila 10050.

PMID- 18613724
TI  - Brownian pump in nonlinear diffusive media.
AB  - A Brownian pump in nonlinear diffusive media is investigated in the presence of
      an unbiased external force. The pumping system is embedded in a finite region and
      bounded by two particle reservoirs. In the adiabatic limit, we obtain the
      analytical expressions of the current and the pumping capacity as a function of
      temperature for normal diffusion, subdiffusion, and superdiffusion. It is found
      that important anomalies are detected in comparison with the normal diffusion
      case. The superdiffusive regime, compared with the normal one, exhibits an
      opposite current for low temperatures. In the subdiffusive regime, the current
      may become forbidden for low temperatures and negative for high temperatures.

PMID- 18613725
TI  - Structure of the oligosaccharide chain of the SR-type lipopolysaccharide of
      Ralstonia solanacearum Toudk-2.
AB  - Aiming at improving classification and taxonomy of Gram-negative phytopathogenic
      bacteria, we studied the structure of the lipopolysaccharide of Ralstonia
      solanacearum. Mild acid hydrolysis of the lipopolysaccharide of strain Toudk-2
      followed by gel chromatography resulted in an O-polysaccharide and two
      oligosaccharide fractions. The smallest-size oligosaccharide fraction was studied
      by sugar analysis, high-resolution electrospray ionization mass spectrometry,
      and, after fractionation by anion-exchange chromatography on HiTrap Q, by one-
      and two-dimensional (1)H and (13)C NMR spectroscopy. It was found that the
      isolated oligosaccharides consist of the lipopolysaccharide core with one O
      polysaccharide repeat (O-unit) attached. The core exists in two major glycoforms
      differing from each other in a lateral octulosonic acid residue, which is either
      D-glycero-D-talo-oct-2-ulosonic acid or 3-deoxy-D-manno-oct-2-ulosonic acid. A
      peculiar feature of the core is the occurrence of 4-amino-4-deoxy-L-arabinose
      nonstoichiometrically linked to a heptose residue. The full structures of the
      core and the biological O-unit as well as the site of the attachment of the O
      unit to the core were established.

PMID- 18613726
TI  - Investigating the existence of nonthermal/specific microwave effects using
      silicon carbide heating elements as power modulators.
AB  - The use of passive heating elements made out of chemically inert sintered silicon
      carbide (SiC) allows microwave transparent or poorly absorbing reaction mixtures
      to be heated under microwave conditions. The cylindrical heating inserts
      efficiently absorb microwave energy and subsequently transfer the generated
      thermal energy via conduction phenomena to the reaction mixture. In the case of
      low to medium microwave absorbing reaction mixtures, the addition of SiC heating
      elements results in significant reductions (30-70%) in the required microwave
      power as compared to experiments performed without heating element at the same
      temperature. The method has been used to probe the influence of microwave power
      (electromagnetic field strength) on chemical reactions. Six diverse types of
      chemical transformations were performed in the presence or absence of a SiC
      heating element at the same reaction temperature but at different microwave power
      levels. In all six cases, the measured conversions/yields were similar regardless
      of whether a heating element was used or not. The applied microwave power had no
      influence on the reaction rate, and only the attained temperature governed the
      outcome of a specific chemical process under microwave conditions.

PMID- 18613727
TI  - Rapid cleavage of unactivated, unstrained amide bonds at neutral pH.
AB  - Building upon the discovery of Suggs and Pires that N-(2-hydroxyethyl)glycine
      amides undergo rapid amide cleavage under mild conditions [ Suggs, J. W. ; Pires,
      R. M. Tetrahedron Lett. 1997, 38, 2227-2230 ], we synthesized the derivatives
      (4aalpha,8beta,8aalpha)-1-ethylamido-8-hydroxydecahydroquinoline ( 4) and
      (4aalpha,8alpha,8abeta)-1-ethylamido-8-hydroxydecahydroquinoline ( 5). These two
      species are conformationally constrained, but steric compression is not
      introduced between the hydroxyl group and the amide functionality it attacks. At
      20 degrees C and slightly basic pH, derivatives 4 and 5 undergo amide cleavage
      with half-lives of 21 min and 14 h, respectively, which correspond to rate
      increases of 251- and 6.3-fold relative to the acyclic analogue N-(2
      hydroxyethyl)glycine amide ( 3).

PMID- 18613728
TI  - Enantioselective copper-catalyzed 1,3-dipolar cycloadditions.

PMID- 18613729
TI  - Gold-catalyzed organic transformations.

PMID- 18613730
TI  - Surface potentials and layer charge distributions in few-layer graphene films.
AB  - Graphene-derived nanomaterials are emerging as ideal candidates for postsilicon
      electronics. Elucidating the electronic interaction between an insulating
      substrate and few-layer graphene (FLG) films is crucial for device applications.
      Here, we report electrostatic force microscopy (EFM) measurements revealing that
      the FLG surface potential increases with film thickness, approaching a "bulk"
      value for samples with five or more graphene layers. This behavior is in sharp
      contrast with that expected for conventional conducting or semiconducting films,
      and derives from unique aspects of charge screening by graphene's relativistic
      low energy carriers. EFM measurements resolve previously unseen electronic
      perturbations extended along crystallographic directions of structurally
      disordered FLGs, likely resulting from long-range atomic defects. These results
      have important implications for graphene nanoelectronics and provide a powerful
      framework by which key properties can be further investigated.

PMID- 18613731
TI  - Optimal control of vaccine distribution in a rabies metapopulation model.
AB  - We consider an SIR metapopulation model for the spread of rabies in raccoons.
      This system of ordinary differential equations considers subpopulations connected
      by movement. Vaccine for raccoons is distributed through food baits. We apply
      optimal control theory to find the best timing for distribution of vaccine in
      each of the linked subpopulations across the landscape. This strategy is chosen
      to limit the disease optimally by making the number of infections as small as
      possible while accounting for the cost of vaccination.

PMID- 18613732
TI  - "Traveling wave" solutions of FitzHugh model with cross-diffusion.
AB  - The FitzHugh-Nagumo equations have been used as a caricature of the Hodgkin
      Huxley equations of neuron firing and to capture, qualitatively, the general
      properties of an excitable membrane. In this paper, we utilize a modified version
      of the FitzHugh-Nagumo equations to model the spatial propagation of neuron
      firing; we assume that this propagation is (at least, partially) caused by the
      cross-diffusion connection between the potential and recovery variables. We show
      that the cross-diffusion version of the model, be- sides giving rise to the
      typical fast traveling wave solution exhibited in the original "diffusion"
      FitzHugh-Nagumo equations, additionally gives rise to a slow traveling wave
      solution. We analyze all possible traveling wave solutions of the model and show
      that there exists a threshold of the cross-diffusion coefficient (for a given
      speed of propagation), which bounds the area where "normal" impulse propagation
      is possible.

PMID- 18613733
TI  - An environment for complex behaviour detection in bio-potential experiments.
AB  - We propose BioS (Bio-potential Study) as a new virtual data analysis and
      management environment. It was devised to cope with the physiological signals, in
      order to manage different data using advanced methods of analysis and to find a
      simple way to decode and interpret data. BioS has been structured as a flexible,
      modular, and portable environment. It includes several modules as data importing
      and loading, data visualization (1D, 2D, 3D), pre-processing (frequency and
      saturation filtering, statistical analysis), spatiotemporal processing such as
      power spectrum, independent component analysis (ICA) in spatial and time domain,
      and nonlinear analysis for the extraction of the maximum Lyapunov exponent and d
      infinity using optimized algorithms. The environment provides a user-friendly
      Graphic User Interface that allows inexperienced users to perform complex
      analyses and to speed up experimental data processing.

PMID- 18613735
TI  - Morphogenesis of the tumor patterns.
AB  - The mathematical modeling of tumor growth allows us to describe the most
      important regularities of these systems. A stochastic model, based on the most
      important processes that take place at the level of individual cells, is proposed
      to predict the dynamical behavior of the expected radius of the tumor and its
      fractal dimension. It was found that the tumor has a characteristic fractal
      dimension, which contains the necessary information to predict the tumor growth
      until it reaches a stationary state. This fractal dimension is distorted by the
      effects of external fluctuations. The model predicts a phenomenon which indicates
      stochastic resonance when the multiplicative and the additive noise are
      correlated.

PMID- 18613734
TI  - The role of feedback in the formation of morphogen territories.
AB  - In this paper, we consider a mathematical model for the formation of spatial
      morphogen territories of two key morphogens: Wingless (Wg) and Decapentaplegic
      (DPP), involved in leg development of Drosophila. We define a gene regulatory
      network (GRN) that utilizes autoactivation and cros-sinhibition (modeled by Hill
      equations) to establish and maintain stable boundaries of gene expression. By
      computational analysis we find that in the presence of a general activator,
      neither autoactivation, nor cross-inhibition alone are sufficient to maintain
      stable sharp boundaries of morphogen production in the leg disc. The minimal
      requirements for a self-organizing system are a coupled system of two morphogens
      in which the autoactivation and cross-inhibition have Hill coefficients strictly
      greater than one. In addition, the GRN modeled here describes the regenerative
      responses to genetic manipulations of positional identity in the leg disc.

PMID- 18613736
TI  - Principal eigenvalue for an elliptic problem with indefinite weight on
      cylindrical domains.
AB  - This paper is concerned with an indefinite weight linear eigenvalue problem in
      cylindrical domains. We investigate the minimization of the positive principal
      eigenvalue under the constraint that the weight is bounded by a positive and a
      negative constant and the total weight is a fixed negative constant.
      Biologically, this minimization problem is motivated by the question of
      determining the optimal spatial arrangement of favorable and unfavorable regions
      for a species to survive. Both our analysis and numerical simulations for
      rectangular domains indicate that there exists a threshold value such that if the
      total weight is below this threshold value, then the optimal favorable region is
      a circular-type domain at one of the four corners, and a strip at the one end
      with shorter edge otherwise.

PMID- 18613737
TI  - An observer for a nonlinear age-structured model of a harvested fish population.
AB  - We consider an age-structured model of a harvested population. This model is a
      discrete-time system that includes a nonlinear stock-recruitment relationship.
      Our purpose is to estimate the stock state. To achieve this goal, we built an
      observer, which is an auxiliary system that uses the total number of fish caught
      over each season and gives a dynamical estimation of the number of fish by age
      class. We analyse the convergence of the observer and we show that the error
      estimation tends to zero with exponential speed if a condition on the fishing
      effort is satisfied. Moreover the constructed observer (dynamical estimator) does
      not depend on the poorly understood stock-recruitment relationship. This study
      shows how some tools from nonlinear control theory can help to deal with the
      state estimation problem in the field of renewable resource management.

PMID- 18613739
TI  - Seir epidemiological model with varying infectivity and infinite delay.
AB  - A new SEIR model with distributed infinite delay is derived when the infectivity
      depends on the age of infection. The basic reproduction number R0, which is a
      threshold quantity for the stability of equilibria, is calculated. If R0 < 1,
      then the disease-free equilibrium is globally asymptotically stable and this is
      the only equilibrium. On the contrary, if R0 > 1, then an endemic equilibrium
      appears which is locally asymptotically stable. Applying a permanence theorem for
      infinite dimensional systems, we obtain that the disease is always present when
      R0 > 1.

PMID- 18613738
TI  - Simulation of single-species bacterial-biofilm growth using the Glazier-Graner
      Hogeweg model and the CompuCell3D modeling environment.
AB  - The CompuCell3D modeling environment provides a convenient platform for biofilm
      simulations using the Glazier-Graner-Hogeweg (GGH) model, a cell-oriented
      framework designed to simulate growth and pattern formation due to biological
      cells' behaviors. We show how to develop such a simulation, based on the hybrid
      (continuum-discrete) model of Picioreanu, van Loosdrecht, and Heijnen (PLH),
      simulate the growth of a single-species bacterial biofilm, and study the roles of
      cell-cell and cell-field interactions in determining biofilm morphology. In our
      simulations, which generalize the PLH model by treating cells as spatially
      extended, deformable bodies, differential adhesion between cells, and their
      competition for a substrate (nutrient), suffice to produce a fingering
      instability that generates the finger shapes of biofilms. Our results agree with
      most features of the PLH model, although our inclusion of cell adhesion, which is
      difficult to implement using other modeling approaches, results in slightly
      different patterns. Our simulations thus provide the groundwork for simulations
      of medically and industrially important multispecies biofilms.

PMID- 18613740
TI  - Modeling and prediction of HIV in China: transmission rates structured by
      infection ages.
AB  - HIV transmission process involves a long incubation and infection period, and the
      transmission rate varies greatly with infection stage. Consequently, modeling
      analysis based on the assumption of a constant transmission rate during the
      entire infection period yields an inaccurate description of HIV transmission
      dynamics and long-term projections. Here we develop a general framework of
      mathematical modeling that takes into account this heterogeneity of transmission
      rate and permits rigorous estimation of important parameters using a regression
      analysis of the twenty-year reported HIV infection data in China. Despite the
      large variation in this statistical data attributable to the knowledge of HIV,
      surveillance efforts, and uncertain events, and although the reported data counts
      individuals who might have been infected many years ago, our analysis shows that
      the model structured on infection age can assist us in extracting from this data
      set very useful information about transmission trends and about effectiveness of
      various control measures.

PMID- 18613741
TI  - Effects of malathion on embryonic development and latent susceptibility to
      trematode parasites in ranid tadpoles.
AB  - We investigated the effects of embryonic exposure to the widely used
      organophosphate malathion (15-600 micro/L) on the early development and latent
      susceptibility of pickerel frog (Rana palustris) tadpoles to the trematode
      parasite Echinostoma trivolvis. The latent effects of contaminant exposure are
      rarely examined but could have important implications for individual survival and
      population viability. Malathion decreased hatching success by 6.5% and viability
      rates by 17% at 600 microg/L, which is a lower concentration than previously
      documented for anuran embryos. Incidence of malformations increased from 0.5% in
      controls to 11.2% in the 600-microg/L malathion treatment. The primary
      malformations documented in the two highest pesticide concentrations were
      ventralization and axial shortening. After seven weeks of development in water
      with no malathion, tadpoles previously exposed as embryos for only 96 h to 60 and
      600 microg/L malathion suffered increased parasite encystment rates when compared
      to controls. Our research identifies embryonic development as a sensitive window
      for establishing latent susceptibility to infection in later developmental
      stages.

PMID- 18613742
TI  - Determination of physicochemical properties of tetrabromobisphenol A.
AB  - Aqueous solubility (Sw), 1-octanol/water partition coefficient (Kow), and vapor
      pressure of the nonionic form of 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol
      (tetrabromobisphenol A or TBBP-A) were measured. From this, enthalpies of
      solution and vaporization were estimated. Furthermore, enthalpy of fusion and
      melting point were measured to estimate subcooled liquid vapor pressure, the
      infinite dilution activity coefficient, and Henry's law constant. Since TBBP-A is
      expected to exit in both ionic and nonionic forms at near neutral pH, pH effects
      on physicochemical properties were also examined. Because of the ionization of
      TBBP-A, Sw increased by five orders of magnitude, while Kow decreased by eight
      orders of magnitude. Furthermore, an analytical model based on mass balance and
      dissociation of TBBP-A was applied to represent the pH dependence.

PMID- 18613743
TI  - Sorption of polar and nonpolar aromatic compounds to two humic acids with varied
      structural heterogeneity.
AB  - The major objective of the present study was to evaluate the correlation between
      structural nature of humic acids (HAs) and sorption affinity of organic compounds
      with varied polarity. We compared the sorption behavior of three aromatic
      compounds-nonpolar phenanthrene (PHEN) and 1,2,4,5-tetrachlorobenzene (TeCB) and
      highly polar 2,4-dichlorophenol (DCP)-to a solid-phase coal humic acid (CHA) and
      a soil humic acid (SHA) suspended in aqueous solution. The structural nature of
      HAs was characterized using elemental analysis, ultraviolet absorbance, diffusive
      reflectance Fourier-transform infrared, and solid-state 13C nuclear magnetic
      resonance. The two tested HAs have very different structural properties: CHA
      consists primarily of poly(methylene)-rich aliphatics with high aromatic content
      and some COO/N-C=O but low polarity, while SHA consists of young materials of
      lignin, carbohydrates, and peptides with high polarity. In response to the
      structural heterogeneity of HAs, sorption of nonpolar and more hydrophobic
      solutes (PHEN, TeCB) to CHA is much greater than that to SHA because of the
      predominance of hydrophobic effects; however, disparities in sorption affinity
      between the two HAs become smaller for polar and less hydrophobic DCP because of
      the major role played by polar interactions. The influence of pH on the sorption
      of different solutes to the two HAs was also discussed. The results of the
      present work highlight the importance of structural heterogeneity of both solutes
      and HAs in the sorption process.

PMID- 18613744
TI  - DNA microarrays detect effects of soil contamination on Arabidopsis thaliana gene
      expression.
AB  - Soil contamination, such as heavy metals and benzene compounds, is a widespread
      problem on military installations. It is important to be able to determine the
      effects of soil contamination before any adverse effects appear in organisms in
      surrounding areas. We examined gene expression in Arabidopsis thaliana grown in
      soil from three sites at the Radford Army Ammunition Plant in Radford, Virginia,
      USA, using DNA microarrays. We analyzed soil, germination, and growth rate to
      compare with the microarray data. Soil contamination affected both external
      phenotype and gene expression. Plants grown in soil with high levels of
      contaminants were chloritic and were smaller than control plants grown in potting
      soil. Plants grown in soil with the highest copper concentration had the lowest
      growth rates and had genes up-regulated across several functional groups. Plants
      grown in soils with elevated lead had many genes down-regulated that were related
      to photosystem II, metabolism, cellular transport, and protein synthesis. Genes
      consistently up-regulated across most microarrays were genes related to
      photosystem I, genes related to water deprivation and oxidative stress response,
      heat shock proteins, and toxin catabolism genes such as glutathiones. DNA
      microarrays, in concert with a model genetic organism such as A. thaliana, were
      an effective assessment tool to determine the presence of toxic substances in
      soil at a site used for the production of military explosives.

PMID- 18613745
TI  - Public-health and individual approaches to antiretroviral therapy: township South
      Africa and Switzerland compared.
AB  - BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in
      resource-limited settings follows a public health approach, which is
      characterised by a limited number of regimens and the standardisation of clinical
      and laboratory monitoring. In industrialized countries doctors prescribe from the
      full range of available antiretroviral drugs, supported by resistance testing and
      frequent laboratory monitoring. We compared virologic response, changes to first
      line regimens, and mortality in HIV-infected patients starting HAART in South
      Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV
      Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We
      included treatment-naive patients aged 16 y or older who had started treatment
      with at least three drugs since 2001, and excluded intravenous drug users. Data
      from a total of 2,348 patients from South Africa and 1,016 patients from the
      Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80
      cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa,
      patients started with one of four first-line regimens, which was subsequently
      changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used
      initially, and these were changed in 539 patients (53%). In most patients HIV-1
      RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence
      interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26%
      (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two
      years. Mortality was higher in South Africa than in Switzerland during the first
      months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during
      months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the
      highly individualised approach in Switzerland, programmatic HAART in South Africa
      resulted in similar virologic outcomes, with relatively few changes to initial
      regimens. Further innovation and resources are required in South Africa to both
      achieve more timely access to HAART and improve the prognosis of patients who
      start HAART with advanced disease.

PMID- 18613746
TI  - Scaling up programmatic management of drug-resistant tuberculosis: a prioritized
      research agenda.

PMID- 18613747
TI  - Surveillance Sans Frontieres: Internet-based emerging infectious disease
      intelligence and the HealthMap project.

PMID- 18613748
TI  - Novel intermolecular iterative mechanism for biosynthesis of mycoketide catalyzed
      by a bimodular polyketide synthase.
AB  - In recent years, remarkable versatility of polyketide synthases (PKSs) has been
      recognized; both in terms of their structural and functional organization as well
      as their ability to produce compounds other than typical secondary metabolites.
      Multifunctional Type I PKSs catalyze the biosynthesis of polyketide products by
      either using the same active sites repetitively (iterative) or by using these
      catalytic domains only once (modular) during the entire biosynthetic process. The
      largest open reading frame in Mycobacterium tuberculosis, pks12, was recently
      proposed to be involved in the biosynthesis of mannosyl-beta-1-phosphomycoketide
      (MPM). The PKS12 protein contains two complete sets of modules and has been
      suggested to synthesize mycoketide by five alternating condensations of
      methylmalonyl and malonyl units by using an iterative mode of catalysis. The
      bimodular iterative catalysis would require transfer of intermediate chains from
      acyl carrier protein domain of module 2 to ketosynthase domain of module 1. Such
      bimodular iterations during PKS biosynthesis have not been characterized and
      appear unlikely based on recent understanding of the three-dimensional
      organization of these proteins. Moreover, all known examples of iterative PKSs so
      far characterized involve unimodular iterations. Based on cell-free
      reconstitution of PKS12 enzymatic machinery, in this study, we provide the first
      evidence for a novel "modularly iterative" mechanism of biosynthesis. By
      combination of biochemical, computational, mutagenic, analytical
      ultracentrifugation and atomic force microscopy studies, we propose that PKS12
      protein is organized as a large supramolecular assembly mediated through specific
      interactions between the C- and N-terminus linkers. PKS12 protein thus forms a
      modular assembly to perform repetitive condensations analogous to iterative
      proteins. This novel intermolecular iterative biosynthetic mechanism provides new
      perspective to our understanding of polyketide biosynthetic machinery and also
      suggests new ways to engineer polyketide metabolites. The characterization of
      novel molecular mechanisms involved in biosynthesis of mycobacterial virulent
      lipids has opened new avenues for drug discovery.

PMID- 18613749
TI  - A short-time scale colloidal system reveals early bacterial adhesion dynamics.
AB  - The development of bacteria on abiotic surfaces has important public health and
      sanitary consequences. However, despite several decades of study of bacterial
      adhesion to inert surfaces, the biophysical mechanisms governing this process
      remain poorly understood, due, in particular, to the lack of methodologies
      covering the appropriate time scale. Using micrometric colloidal surface
      particles and flow cytometry analysis, we developed a rapid multiparametric
      approach to studying early events in adhesion of the bacterium Escherichia coli.
      This approach simultaneously describes the kinetics and amplitude of early steps
      in adhesion, changes in physicochemical surface properties within the first few
      seconds of adhesion, and the self-association state of attached and free-floating
      cells. Examination of the role of three well-characterized E. coli surface
      adhesion factors upon attachment to colloidal surfaces--curli fimbriae, F
      conjugative pilus, and Ag43 adhesin--showed clear-cut differences in the very
      initial phases of surface colonization for cell-bearing surface structures, all
      known to promote biofilm development. Our multiparametric analysis revealed a
      correlation in the adhesion phase with cell-to-cell aggregation properties and
      demonstrated that this phenomenon amplified surface colonization once initial
      cell-surface attachment was achieved. Monitoring of real-time physico-chemical
      particle surface properties showed that surface-active molecules of bacterial
      origin quickly modified surface properties, providing new insight into the
      intricate relations connecting abiotic surface physicochemical properties and
      bacterial adhesion. Hence, the biophysical analytical method described here
      provides a new and relevant approach to quantitatively and kinetically
      investigating bacterial adhesion and biofilm development.

PMID- 18613750
TI  - A gene wiki for community annotation of gene function.

PMID- 18613751
TI  - Development and validation of a congener-specific photodegradation model for
      polybrominated diphenyl ethers.
AB  - With the phaseout of the manufacture of some polybrominated diphenyl ether (PBDE)
      formulations, namely penta-brominated diphenyl ether (BDE) and octa-BDE, and the
      continued use of the deca-BDE formulation, it is important to be able to predict
      the photodegradation of the more highly brominated congeners. A model was
      developed and validated to predict the products and their relative concentrations
      from the photodegradation of PBDEs. The enthalpies of formation of the 209 PBDE
      congeners were calculated, and the relative reaction rate constants were
      obtained. The predicted reaction rate constants for PBDEs show linear correlation
      with previous experimental results. Because of their large volume use, their
      presence in the environment, and/or importance in the photodegradation of the
      deca-BDE formulation, BDE-209, BDE-184, BDE-100, and BDE-99 were chosen for
      further ultraviolet photodegradation experiments in isooctane. The
      photodegradation model successfully predicted the products of the photochemical
      reactions of PBDEs in experimental studies. A gas chromatography retention time
      model for PBDEs was developed using a multiple linear regression analysis and,
      together with the photodegradation model and additional PBDE standards, provided
      a way to identify unknown products from PBDE photodegradation experiments. Based
      on the results of the photodegradation experiments, as well as the model
      predictions, it appears that the photodegradation of PBDEs is a first-order
      reaction and, further, that the rate-determining step is the stepwise loss of
      bromine. Our results suggest that, based on photodegradation, over time, BDE-99
      will remain the most abundant penta-BDE, while BDE-49 and BDE-66 will increase
      greatly and will be comparable in abundance to BDE-47.

PMID- 18613752
TI  - Canine and bovine Neospora caninum control sera examined for cross-reactivity
      using Neospora caninum and Neospora hughesi indirect fluorescent antibody tests.
AB  - Neospora caninum is a well known protozoan parasite of domestic and wild animals.
      Neospora hughesi is a closely related protozoan with an unknown life cycle, host
      range, and infection prevalence. Many serologic surveys of N. caninum have been
      performed without consideration of potential cross-reactions with N. hughesi,
      which could confound results. The aim of this study was to investigate whether
      postexposure sera from animals experimentally infected with N. caninum exhibit
      significant reactivity differences when tested using N. caninum and N. hughesi
      Immunofluorescent Antibody Tests (IFAT). Pre- and postinfection serum samples
      from 10 dogs, 20 calves, and 17 cows were tested by dual IFATs. All pre-exposure
      samples for N. caninum tested seronegative for both organisms. All postexposure
      samples that were seropositive for N. caninum were also positive for N. hughesi,
      although N. hughesi antibody titers were usually 1 dilution lower (P < 0.02).
      Serologic surveys for N. caninum may be confounded by cross-reacting titers with
      N. hughesi, but true positive N. caninum antibody titers are greater than, or
      equal to, cross-reacting N. hughesi antibody titers.

PMID- 18613754
TI  - Presidential address: nothing succeeds like excess.

PMID- 18613755
TI  - Ecotoxicological environmental risk limits for total petroleum hydrocarbons on
      the basis of internal lipid concentrations.
AB  - A method is described for deriving ecotoxicological environmental risk limits
      (ERLs) for total petroleum hydrocarbons (TPH). Toxicity data for two oil types
      (light and heavy) to benthic organisms and corresponding estimated internal lipid
      concentrations, calculated by equilibrium partitioning, are used as a measure of
      toxicity by narcosis. It is assumed that uptake by organisms takes place from the
      aqueous phase, and for partitioning, both oil droplets or coating and organic
      carbon of sediment are taken into account. To distinguish between the different
      fractions of TPH, the method used is based on a fraction analysis approach in
      which aliphatic and aromatic compounds are regarded separately and both are
      further divided into different fractions. A toxic unit approach is applied to
      these fractions to take additivity into account. Lethality of the lighter oil
      type (internal concentration 28-204 mmol/Llipid) was in good agreement with data
      on internal concentrations retrieved from the literature. For the heavier oil
      type the observed toxicity was slightly higher and can probably be attributed to
      physical soiling of the organisms by oil or oxygen depletion due to
      biodegradation of the oil. For deriving ERLs, chronic endpoints are considered.
      The most sensitive chronic endpoints appear to be similar for both types of oil.
      The distribution of estimated total internal concentrations for chronic endpoints
      (1.38-149 mmol/Llipid) is used as a basis for the ERLs. The resulting ERLs for
      the mixture of TPH are comparable with ERLs for single compounds.

PMID- 18613756
TI  - Vascular endothelial growth factor polymorphisms -1154 G/A and -460 C/T are not
      associated with VEGF mRNA expression and susceptibility to sporadic colon cancer.
AB  - Vascular endothelial growth factor (VEGF) is important mediator of angiogenesis,
      and its expression in colorectal tumors is related to tumor progression. VEGF
      expression has been detected in normal mucosa, primary colon cancers, and
      metastatic tumors, and patients with low VEGF expression have a better survival
      rate. In addition, anti-VEGF monoclonal antibody improves overall survival when
      used in combination with existing metastatic colorectal cancer therapy.
      Therefore, prediction of VEGF production based on individual genetic background
      might be important for predicting the course of the disease and the efficacy of
      anticancer treatment. The number of studies evaluating the influence of VEGF
      polymorphisms on cancer susceptibility is growing; however, their results are
      often conflicting. In addition, these studies are rarely accompanied with the
      expression analysis examining the influence of these polymorphisms on mRNA
      expression in tumor tissue. In this study, we have examined the influence of VEGF
      polymorphisms -1154 G/A and -460 C/T on VEGF mRNA expression and susceptibility
      to sporadic colon cancer by real-time PCR-SNP and mRNA expression analysis. The
      study included population control group consisting of 160 unrelated volunteers
      and a group of 160 patients with sporadic colon cancer. According to our results,
      -1154 G/A and -460 C/T do not influence VEGF mRNA expression in colorectal tumors
      and susceptibility to sporadic colon cancer, although the role of other
      polymorphisms cannot be excluded.

PMID- 18613757
TI  - Bio-engineering urothelial cells for bladder tissue transplant.
AB  - BACKGROUND: The past decade has seen a surge of interest in bladder tissue
      engineering research, with the anticipation that it will influence future
      urological practice by providing functional tissue substitutes to replace
      diseased or dysfunctional tissues. OBJECTIVE: To describe bladder tissue
      engineering strategies being investigated, with emphasis on urothelial cell
      biology and to discuss some of the challenges that must be addressed to ensure
      that this technique will find a niche in urological practice. METHODS: A review
      of published literature. RESULTS/CONCLUSION: In vitro-propagated urothelial cells
      have been incorporated into a number of bladder engineering strategies, including
      reconstructions using natural or synthetic biomaterials and cell-engineering
      approaches, where the urothelium is combined with reconfigured, vascularised host
      smooth muscle grafts. Although results and quality of reporting are mixed, the
      consensus is of progress being made towards bio-engineered bladders becoming a
      clinical reality once unresolved research and translational issues have been
      addressed.

PMID- 18613758
TI  - Combining stem cells and exon skipping strategy to treat muscular dystrophy.
AB  - BACKGROUND: Muscular dystrophies are characterized by primary wasting of skeletal
      muscle. Mutations in the dystrophin gene cause hereditary muscular diseases such
      as Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD), the
      most severe form. Characterization of the dystrophin gene and evidence that
      different types of adult stem cells are capable of muscle regeneration has lead
      to the development of potential gene therapy and stem cell treatments for DMD.
      OBJECTIVES: The main goal is to combine gene modification strategies with cell
      mediated therapies. This approach could permit autologous transplantation of
      cells, minimizing the risk of implant rejection. RESULTS/CONCLUSION: The
      combination of gene and stem cell approaches seems to be most promising,
      particularly intra-arterial injections of the patient's own stem cells transduced
      by antisense oligonucleotide technology. This approach should offer the chance to
      distribute the autologous corrected stem cells to the whole body musculature
      providing a clinical benefit for dystrophic patients.

PMID- 18613760
TI  - Catalytic DNAzymes: derivations and functions.
AB  - BACKGROUND: Although catalytic RNA enzymes (CRzs) are naturally occurring in many
      organisms, their DNA counterparts (CDzs) were developed by in vitro
      selection/evolution from random sequence libraries. OBJECTIVE: To provide a brief
      overview of how CDzs have been selected in vitro, and of their properties and
      functions, as well as their possible future utility. METHODS: We concentrated on
      examples of 'direct' selection of CDzs. Many CDzs have been used in biological
      settings, for example downregulation of target mRNAs, while many more recent
      applications use CDzs in biosensor and nanotechnology settings. CONCLUSIONS:
      Although much work has concentrated on using CDzs for regulating gene expression,
      their potential as nucleic acid medicines has diminished substantially,
      supplanted by simple antisense oligonucleotides and, more recently, by small
      interfering RNAs (siRNAs). It seems unlikely that CDzs will have clinical
      utility. In contrast, they are likely to have significant potential in the
      sensor/nanotechnology arena.

PMID- 18613759
TI  - Biofunctionalized targeted nanoparticles for therapeutic applications.
AB  - BACKGROUND: The development of nanoparticles for the delivery of therapeutic
      agents has introduced new opportunities for the improvement of medical treatment.
      Recent efforts have focused on developing targeted nanoparticles, which are
      formulated by (for therapeutic delivery) functionalizing nanoparticle surfaces
      with targeting molecules, such as antibodies, peptides, small molecules and
      oligonucleotides. OBJECTIVES: To review the state of targeted nanoparticles
      development. METHODS: The authors discuss the nanoparticle platforms for
      therapeutic delivery, targeting molecules and the biofunctionalized targeted
      nanoparticles currently in development. RESULTS/CONCLUSIONS: Biofunctionalized
      targeted nanoparticles have demonstrated exciting results in preclinical studies.
      With continued improvements, they may fulfill their potential as therapeutics
      carriers that can deliver the maximum dose to diseased tissue while minimizing
      effects on normal cells.

PMID- 18613761
TI  - Creating protein biocatalysts as tools for future industrial applications.
AB  - BACKGROUND: Biocatalysts provide an economical and energy-efficient alternative
      to traditional chemical manufacturing processes. For processes where biocatalysts
      currently do not exist or existing protein catalysts function poorly, there is a
      tremendous need to discover new protein catalysts that function in industrial
      settings. The protein engineering community has traditionally relied on cell
      based techniques in 96-well format to evolve new catalysts or improve existing
      enzymes. OBJECTIVE: This review examines recent progress made in many display
      technologies, providing powerful alternatives for generating novel enzymes with
      altered specificity or altogether new types of function. METHODS: Library
      creation methods and display technologies that are commonly used in conjunction
      with enzyme evolution are discussed. CONCLUSION: We conclude with an expert
      opinion on future trans-disciplinary approaches that combine directed evolution
      with computational design as novel platforms for rapidly discovering new types of
      catalytic function.

PMID- 18613762
TI  - The potential use of AKAP18delta as a drug target in heart failure patients.
AB  - BACKGROUND: The adrenaline-beta-adrenoreceptor-cAMP-protein kinase A signaling
      pathway regulates heart rate and contractility. Although changes in contractility
      are associated with cardiovascular disease, surprisingly few drugs are available
      that modulate the cardiac myocyte cAMP system. Beta-blocking agents reduce cAMP
      levels only by 50%. OBJECTIVE: Compounds that interfere with the pathway at other
      levels are wanted as they may provide new tools for treatment of heart failure
      used alone or together with beta-blockers and may make therapy more potent and/or
      more targeted and avoid side effects. METHODS: Original findings and strategies
      for targeting protein-protein interactions are reviewed. RESULTS/CONCLUSION: We
      have shown that A-kinase anchoring protein (AKAP)18delta is important for
      organizing the molecular machinery that mediates adrenergic control of calcium
      reabsorption into sarcoplasmic reticulum. Calcium reabsorption is essential for
      relaxation and filling of the heart and is the rate-limiting step for making the
      heart beat faster in response to adrenaline or noradrenaline. We conclude that
      targeting AKAP18delta may have application in manipulating calcium reabsorption
      and protecting the heart from adrenergic pacing at the level of specific
      signaling events in heart failure patients.

PMID- 18613763
TI  - New therapeutic applications for the anticoagulant, activated protein C.
AB  - BACKGROUND: Activated protein C (APC) is derived from its precursor, protein C
      (PC). Originally thought to be synthesised exclusively by the liver, recent
      reports have shown that PC is also produced by endothelial cells, smooth muscle
      cells, keratinocytes and some leukocytes. OBJECTIVE: To provide an update on the
      emerging therapeutic effects of APC. RESULTS/CONCLUSION: APC functions as an
      anticoagulant with cytoprotective, anti-inflammatory and antiapoptotic
      properties. In vitro and preclinical data have revealed that APC exerts its
      protective effects via an intriguing mechanism requiring endothelial protein C
      receptor and protease activated receptor-1. Approved as a therapeutic agent for
      severe sepsis, APC is emerging as a potential treatment for a number of
      autoimmune and inflammatory diseases including spinal cord injury, asthma,
      chronic wounds and possibly rheumatoid arthritis. The future therapeutic uses of
      APC look very promising.

PMID- 18613764
TI  - Recombinant antibodies for cancer therapy.
AB  - BACKGROUND: Recombinant antibodies have evolved into successful therapeutics with
      10 approved for cancer and more in the pipeline. Four of the top ten cancer
      therapy drugs are recombinant antibodies. OBJECTIVES: To survey the current state
      of-the-art highlighting the reasons for this success and looking ahead to the
      next generation of antibody therapy. METHODS: An analysis was carried out to
      identify preclinical and clinical examples and the underlying concepts and
      mechanisms that have shown how to design better therapies. RESULTS/CONCLUSIONS:
      Greater understanding of the molecular basis of cancer has led to improved
      antibodies and a greater selection of targets. Fine tuning of successful
      antibodies through modification of glycosylation, affinity, size and other
      parameters are paying dividends. Fc-engineering is likely to be predominant in
      the near future but conjugates, fragments and fusion proteins will continue to be
      developed and find their place in the arsenal of antibody therapeutics.

PMID- 18613765
TI  - Using immunoglobulins in muscular disease treatment.
AB  - BACKGROUND: Intravenous immunoglobulins (IVIg) have been proven in the past two
      decades to be potent immunomodulators. This led to the licensing and
      recommendation of IVIg as first-line treatment for Kawasaki disease, idiopathic
      thrombocytopenic purpura and Guillain-Barre syndrome. OBJECTIVE: To review the
      evidence and indications for the use of IVIg in the treatment of muscular
      diseases. METHODS: Literature search in PubMed and of further literature cited in
      these articles. RESULTS/CONCLUSION: There are small randomised controlled trials
      that demonstrate the efficacy of IVIg in dermatomyositis, myasthenic crisis,
      Lambert-Eaton myasthenic syndrome and stiff-person syndrome. However, since there
      are also alternative treatments IVIgs are mostly used in these diseases as
      alternatives when other therapeutic approaches have failed.

PMID- 18613766
TI  - Approved monoclonal antibodies for cancer therapy.
AB  - BACKGROUND: Monoclonal antibodies are a rapidly expanding class of agents for the
      treatment of cancer. In 1997 rituximab became the first approved monoclonal
      antibody for the treatment of low grade B cell lymphoma. Since then several
      monoclonal antibodies have received approval from the United States Food and Drug
      Administration (US FDA) for the treatment of a variety of solid tumors and
      hematological malignancies. OBJECTIVE/METHODS: To review the literature using
      Medline and summarize the mechanisms of action, indications and outcome of
      treatment of currently approved monoclonal antibodies used in clinical practice
      for patients with solid tumors and hematologic malignancies. RESULTS/CONCLUSIONS:
      An overview of the FDA approved monoclonal antibodies is provided. Monoclonal
      antibodies are currently used as the standard of care as first and second line
      therapy for a number of hematologic malignancies and solid tumors. Over the next
      5 - 10 years additional monoclonal antibodies and monoclonal antibody conjugates
      will be approved by the US FDA and will dramatically affect the standard of care
      of many cancers.

PMID- 18613767
TI  - Biofilms in nephrology.
AB  - BACKGROUND: Biofilms are bacterial communities ubiquitous to moist environments.
      Biofilm formation is a factor in the development and persistence of infectious
      diseases. In clinical nephrology, biofilms influence the development of kidney
      stones and affect dialysis systems, including peritoneal and central venous
      catheters. Biofilms also play critical roles in persistent and resistant renal
      and urinary tract infections. OBJECTIVE: To describe the physiology of biofilms
      and potential effects of biofilms upon infectious diseases, focusing on the role
      of biofilms in kidney stones, indwelling catheters and dialysis equipment.
      METHODS: A literature search with Medline to identify pertinent English language
      articles published up to early 2008 using the keywords biofilm, nephrology,
      renal, calculi and infection. RESULTS/CONCLUSION: Biofilms are ubiquitous in
      clinical nephrology and play a role in the pathogenesis of resistant infections.
      Strategies for reducing the effects of biofilms in nephrology are described.

PMID- 18613768
TI  - Apomab: an agonist monoclonal antibody directed against Death Receptor 5/TRAIL
      Receptor 2 for use in the treatment of solid tumors.
AB  - BACKGROUND: Apomab is a pro-apoptotic anticancer agonist monoclonal antibody
      against Death receptor 5 (DR5)/TNF-related apoptosis inducing ligand-receptor 2
      (TRAIL-R2). OBJECTIVE: To review available preclinical and clinical data and
      compare Apomab with similar agents. METHODS: Manuscripts were identified (PubMed)
      using the terms TRAIL-R2, DR5 and Apomab. Abstracts from major oncology meetings
      in 2005 - 2008 were hand-searched. RESULTS/CONCLUSION: Apomab demonstrates
      preclinical activity against a range of solid tumors, both as monotherapy and in
      combination with cytotoxics. Clinical data are limited but Apomab exposures
      appear compatible with intermittent dosing alongside standard chemotherapy
      regimens. Transaminitis has been noted in 1 out of 37 patients but the true
      frequency and severity of this and other toxicities cannot yet be determined.
      Apomab has shown early signs of anticancer activity in heavily pretreated
      patients. Several similar agents are at similar stages of development. No direct
      comparisons have yet been undertaken but potential differences between these
      agents are discussed.

PMID- 18613769
TI  - Recent advances with a virosomal hepatitis A vaccine.
AB  - BACKGROUND: Epaxal, a virosomal vaccine against hepatitis A virus (HAV)
      infection, has been in use for nearly 15 years, especially among at-risk adults.
      Recent studies have shown that it is also a potent vaccine for children.
      OBJECTIVE: To summarise recent advances of Epaxal Junior (0.25 ml, paediatric
      formulation). METHODS: Published papers reporting results on the virosomal HAV
      vaccine were abstracted and reviewed. RESULTS/CONCLUSION: In a comparative
      randomised trial, the paediatric dose was found to be highly immunogenic and non
      inferior to the standard dose with respect to seroprotection rates. The
      concomitant administration of virosomal HAV vaccine with routine childhood
      vaccines was investigated in another trial. The virosomal HAV vaccine did not
      interact with the antibody response of routine childhood vaccines which in turn
      did not reduce the antibody response to HAV. In countries that recommend
      immunisation against hepatitis A, this virosomal vaccine is an excellent
      candidate with few side effects at the site of injection.

PMID- 18613770
TI  - Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of
      hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic
      surgery.
AB  - BACKGROUND: Plasma kallikrein plays a major role in the contact (kallikrein
      kinin) cascade producing bradykinin. Bradykinin is a vasodilator, which increases
      vascular permeability, activates inflammation and produces pain. Plasma
      kallikrein is also crosslinked to the coagulation system and the complement
      cascade. OBJECTIVE: Ecallantide (DX-88) is a potent and specific inhibitor of
      plasma kallikrein. Ecallantide is a recombinantly produced and engineered small
      protein based on the first Kunitz domain of human tissue factor pathway
      inhibitor. It was identified through phage display technology. METHODS: The
      search terms 'ecallantide', 'DX-88' and 'hereditary angioedema' were entered into
      Pubmed/Medline, ClinicalTrials and Google. RESULTS/CONCLUSION: At present, the
      drug is being studied for two major indications. First, the results for the
      treatment of hereditary angioedema are promising. Second, a prospective
      randomised multi-centre trial for the reduction of blood loss during on-pump
      cardiothoracic surgery will be terminated in October 2008.

PMID- 18613771
TI  - Defibrotide: a review on clinical use and future development.
AB  - BACKGROUND: Defibrotide is a deoxyribonucleic acid derivative that has been
      developed for the treatment of different vascular disorders. OBJECTIVE: The
      authors reviewed the literature to give due representation to the spectrum of
      pharmacological properties and clinical application of this drug, evaluating
      consolidate and innovative application. METHODS: The authors used PubMed from
      November 1982 to December 2007 and meeting abstracts (form American Society of
      Hematology Annual Meeting) with updated data as the sources for this review and
      selecting the most relevant papers when two or more articles covered the same
      point of interest. CONCLUSIONS: Defibrotide has been used effectively in the
      treatment of endothelial complications of allogeneic stem cell transplantation
      and recent preclinical evidences suggest an antiangiogenic effect and an
      anticancer activity. Further in vivo and in vitro investigations are needed.

PMID- 18613772
TI  - Idiotype vaccine strategies for improving outcomes in follicular lymphoma.
AB  - BACKGROUND: Follicular lymphoma (FL) is a common indolent lymphoma associated
      with a relapsing course. Preclinical models and clinical studies demonstrate that
      immunizing FL patients against their own tumor idiotype induces humoral and
      cellular immunity and supresses tumor growth. METHODS: We review idiotype vaccine
      strategies that have been tested in FL patients in frontline and relapsed
      settings to examine the safety and efficacy of this approach. RESULTS: Several
      Phase II trials of recombinant or hybridoma-produced vaccines or vaccines
      combined with other immunotherapy demonstrate cellular and humoral anti-idiotype
      responses and clinical responses, indicating that idiotype vaccines provide
      promise for improving FL outcomes. CONCLUSION: These strategies are now being
      evaluated in Phase III trials but have yet to demonstrate clear advantages in
      progression-free survival.

PMID- 18613773
TI  - C1 inhibitor: just a serine protease inhibitor? New and old considerations on
      therapeutic applications of C1 inhibitor.
AB  - C1 inhibitor is a potent anti-inflammatory protein as it is the major inhibitor
      of proteases of the contact and the complement systems. C1-inhibitor
      administration is an effective therapy in the treatment of patients with
      hereditary angioedema (HAE) who are genetically deficient in C1 inhibitor. Owing
      to its ability to modulate the contact and complement systems and the convincing
      safety profile, plasma-derived C1 inhibitor is an attractive therapeutic protein
      to treat inflammatory diseases other than HAE. In the present review we give an
      overview of the biology of C1 inhibitor and its use in HAE. Furthermore, we
      discuss C1 inhibitor as an experimental therapy in diseases such as sepsis and
      myocardial infarction.

PMID- 18613774
TI  - Placental-derived and expanded mesenchymal stromal cells (PLX-I) to enhance the
      engraftment of hematopoietic stem cells derived from umbilical cord blood.
AB  - For the past 40 years, bone marrow transplantation (BMT) has become standard
      therapy to re-establish marrow function in patients with damaged or defective
      bone marrow. A human leukocyte antigen-matched sibling is the donor of choice for
      patients needing transplantation of allogeneic hematopoietic stem cells (HSCs).
      As most patients do not have an acceptable matched, related donor, the National
      Marrow Donor Program has been established to match volunteer bone marrow donors
      with potential recipients who require BMT. Although transplantation of HSCs from
      an unrelated donor can be an effective therapy for a variety of malignant and non
      malignant diseases, it remains complicated because of treatment-related morbidity
      and mortality, which has led to the investigation of alternative sources of HSCs
      such as umbilical cord blood (UCB). This review highlights the advantages and
      disadvantages of UCB and recent developments that address its disadvantages. This
      includes the use of a placenta-expanded mesenchymal stromal cell product (PLX-I)
      being developed by Pluristem Therapeutics, Inc. and our opinion about the
      potential of this product.

PMID- 18613775
TI  - How is extinction risk related to population-size variability over time? A family
      of models for species with repeated extinction and immigration.
AB  - It is well known that for an isolated population, the probability of extinction
      is positively related to population size variation: more variation is associated
      with more extinction. What, then, is the relation of extinction to population
      size variation for a population embedded in a metapopulation and subjected to
      repeated extinction and recolonization? In this case, the extinction risk can be
      measured by the extinction rate, the frequency at which local extinction occurs.
      Using several population dynamics models with immigration, we find, in general, a
      negative correlation between extinction and variation. More precisely, with
      increasing length of the time series, an initially negative regression
      coefficient first becomes more negative, then becomes less negative, and
      eventually attains positive values before decreasing again to 0. This pattern
      holds under substantial variation in values of parameters representing species
      and environmental properties. It is also rather robust to census interval length
      and the fraction of missed individuals but fails to hold for high thresholds
      (population size values below which extinction is deemed to occur) when quasi
      extinction rather than true extinction is represented. The few departures from
      the initial negative correlation correspond to populations at risk: low growth
      rate or frequent catastrophes.

PMID- 18613776
TI  - Tubeless percutaneous nephrolithotomy for staghorn stones.
AB  - PURPOSE: To assess the outcome and safety of tubeless percutaneous
      nephrolithotomy (PCNL) to treat patients with staghorn stones. PATIENTS AND
      METHODS: Between March 2006 and March 2007, 75 patients underwent 82 PCNLs at our
      hospital. Of that total, 42 procedures were done without a nephrostomy tube
      (tubeless group) and 40 procedures were done with insertion of a nephrostomy tube
      at the end of the procedure (standard group). RESULTS: The mean age was 41.55 +/-
      15.15 years and 50.29 +/- 9.42 years in the tubeless group and the standard
      group, respectively. Seven patients had bilateral stones. None of our patients
      had organ trauma or any other significant complication. The average operative
      time was shorter in the tubeless group than in the standard group (93.76 v 109.98
      minutes, respectively; P = 0.03). The mean analgesic doses given postoperatively
      were 79.17 +/- 62.2 and 93.75 +/- 40.7 mg of meperidine in the tubeless group and
      the standard group, respectively, with no statistically significant difference.
      The mean postoperative hospital stay was 1.7 +/- 0.6 days in the tubeless group
      and 4 +/- 1.6 days in the standard group (P < 0.0001). The stone-free rate was 37
      units (88.09%) and 35 units (87.5%) units in the tubeless and standard groups,
      respectively. CONCLUSIONS: Complications, operative time, and the length of
      hospitalization in selected patients undergoing tubeless PCNL were all lower than
      those seen in the standard group. Tubeless PCNL was thus found to be safe and
      effective, even in patients with staghorn stones.

PMID- 18613777
TI  - Comparison of photoselective vaporization of the prostate and transurethral
      resection of the prostate: a prospective nonrandomized bicenter trial with 2-year
      follow-up.
AB  - PURPOSE: To present our 2-year data comparing photoselective vaporization of the
      prostate (PVP) and transurethral resection of the prostate (TURP) for patients
      suffering from lower urinary tract symptoms (LUTS) secondary to benign prostatic
      hyperplasia (BPH). PATIENTS AND METHODS: In this prospective non-randomized
      study, 210 patients with a prostate volume <70 mL underwent PVP (112) or TURP
      (98). Functional follow-up included measurement of maximum urinary flow rate
      (Q(max)), post-void residual urine volume (PVR), International Prostate Symptom
      Score (IPSS), and quality-of-life score (QoL) within a 24-month period. While
      anticoagulant therapy was discontinued before the operation in the TURP group, it
      was not discontinued in the PVP group. RESULTS: Baseline characteristics of both
      groups were similar. Mean operative time was 55.5 +/- 21.8 minutes for PVP and
      46.0 +/- 8.7 minutes for TURP (P < 0.001). No statistically significant
      difference was observed between postoperative serum sodium and hemoglobin values
      in both groups (P > 0.05). Catheter indwelling time and hospitalization time of
      the PVP group were shorter than those of the TURP group (P < 0.001). In both
      groups, an immediate and highly significant improvement of Q(max), PVR, IPSS, and
      QoL was evident. Within 24 months urethral stricture in 3 patients after TURP and
      bladder neck contracture in 2 patients after PVP were observed. CONCLUSIONS: The
      postoperative micturition improvement was significant and lasting, and was
      equivalent in both groups. The rate of complications was equally low with both
      procedures. PVP had the advantage of shorter hospitalization and catheter
      indwelling times and no need for discontinuation of anticoagulant therapy
      compared to TURP.

PMID- 18613778
TI  - Evidence-based instrumentation for flexible ureteroscopy: a review.
AB  - Instrumentation is the key to success in endourology. Indeed, endourology could
      be redefined as "enginurology," as the marriage between engineering and urology,
      and developing instrumentation to improve patient outcomes is the key facilitator
      in the advancement of minimally-invasive techniques. This review article will
      identify the evidence base that supports our current recommendations for
      equipment used during ureteroscopy.

PMID- 18613779
TI  - Transperineal microwave thermoablation in patients with obstructive benign
      prostatic hyperplasia: a phase I clinical study with a new mini-choked microwave
      applicator.
AB  - PURPOSE: To evaluate the tolerability and safety of a newly designed probe for
      trans-perineal microwave thermoablation (TPMT) of the prostate in patients with
      benign prostatic hyperplasia (BPH), and the in vivo microwave effects on
      prostatic tissue. PATIENTS AND METHODS: Nine patients with obstructive BPH who
      were candidates for open prostatectomy were selected for this study. Under local
      anesthesia and transrectal ultrasound monitoring, all patients underwent a single
      standardized application of TPMT. The visual analog scale (VAS) and Short Form-36
      health survey (SF-36) questionnaire were administered to each patient prior to,
      during, and 1 month after TPMT in order to evaluate pain and quality of life.
      Then the International Index of Erectile Function (IIEF-5) and International
      Prostate Symptom Score (IPSS) questionnaires were administered to each patient at
      baseline and 1 month after prostatectomy in order to evaluate sexual and urinary
      function, respectively. Then all patients were divided into three groups and
      underwent open prostatectomy 7, 15, and 30 days after TPMT, respectively. The
      prostatic adenomas were then evaluated by a pathologist. RESULTS: No adverse
      events from TPMT treatment were noted. In particular, no patients reported local,
      pelvic, or abdominal pain during the procedure or subsequent alterations of
      defecation rhythm, ano-rectal/intestinal problems, or hematuria. No differences
      in quality of life or in sexual function were reported. The diameters of the
      lesions obtained with TPMT treatment ranged from 16 to 18.1 mm in all patients.
      Quasi-spheroid lesions with a well-defined area of complete coagulative necrosis
      were documented in all removed adenomas 7, 15, and 30 days after TMPT.
      CONCLUSIONS: The AMICA-PROBE is a safe, well-tolerated, and repeatable method to
      treat BPH with microwave thermotherapy. The spheroid lesions obtained
      demonstrated the maximal control over the radial and longitudinal coagulative
      effects of the therapy. Phase II studies are needed to further evaluate the
      efficacy of this new probe.

PMID- 18613780
TI  - Failure of percutaneous endoscopic resection of a renal cystic nephroma on longer
      term follow-up.
AB  - In 2005 we reported in this journal the treatment of cystic nephroma, a rare but
      presumed benign renal tumor, with percutaneous resection. Initial follow-up
      confirmed removal of the intra-pelvic portion of the cystic nephroma and
      persistence of the unresected intra-parenchymal portion. Surveillance with
      computed tomography revealed gradual regrowth of the mass, ultimately resulting
      in a size greater than that at the time of initial resection. Laparoscopic
      radical nephrectomy without adrenalectomy revealed benign cystic nephroma.

PMID- 18613781
TI  - Laparoscopic retroperitoneal lymph node dissection for low-stage testicular
      cancer.
AB  - BACKGROUND AND PURPOSE: Current management options for low-stage mixed malignant
      germ-cell testicular tumors (MMGCT) after radical orchiectomy include
      surveillance, chemotherapy, or retroperitoneal lymph node dissection (RPLND). The
      open RPLND is the surgical gold standard and has been duplicated laparoscopically
      with confirmed diagnostic effectiveness; however, its therapeutic oncologic value
      in MMGCT has never been proven. We present our laparoscopic RPLND (L-RPLND) data
      for low-stage MMGCT and paratesticular rhabdomyosarcoma. PATIENTS AND METHODS:
      Retrospective chart reviews were performed for patients who underwent L-RPLND at
      our institution for low clinical stage MMGCT and paratesticular rhabdomyosarcoma
      from May 2003 to December 2007. Patient data were compiled for surgical and
      clinical variables. RESULTS: A total of 26 L-RPLND procedures were completed, 3
      for paratesticular rhabdomyosarcoma. Mean operative time was 250 minutes (range
      176-369 min); estimated blood loss was 145 mL (range 50-500 mL); lymph node count
      was 23.8 (range 8-48); and hospital stay was 1.5 days (range 1-3 d). Four
      patients underwent postchemotherapy L-RPLND for residual nodes (1.1-2.9 cm).
      There were no conversions to an open procedure, blood transfusions, or operative
      complications. Chemotherapy was instituted in five of six patients with
      pathologic stage II disease. Mean follow-up was 23.7 months without
      retroperitoneal disease recurrence. CONCLUSION: L-RPLND as a diagnostic and
      therapeutic tool provides the benefits of a minimally invasive approach to MMGCT.
      It is the procedure of choice at our institution for low-stage MMGCT and
      paratesticular rhabdomyosarcoma.

PMID- 18613782
TI  - Adjustable continence therapy for treatment of recurrent female urinary
      incontinence.
AB  - PURPOSE: The Adjustable Continence Therapy (ACT) device has been developed for
      the treatment of recurrent stress urinary incontinence resulting from intrinsic
      sphincter deficiency (ISD) by increasing urethral coaptation. We critically
      evaluated the technique and its results. METHODS: The ACT device consists of two
      balloons each attached to an injectable port placed in the labia majora. The port
      enables postoperative adjustment in balloon coaptation pressure. All 49 patients
      had previously failed anti-incontinence surgery. Each patient was implanted with
      the ACT device and assessed by preoperative and postoperative overall impression,
      incontinence quality of life questionnaire, and visual analog scale; 38 of the 49
      subjects had a minimum of 1 year of data collected, including pad use, number of
      adjustments needed, and complications. RESULTS: Mean operative time was 20.3
      minutes (range 10-30 minutes), with 88% of implantations performed using local or
      regional anesthesia. Balloon adjustments were needed in 62%; 68% of patients
      reported being dry and 16% improved. Complications included migration (12%),
      balloon failure (3.6%), and erosion (4%). CONCLUSION: The ACT device provided
      significant improvement in at last 70% of patients with recurrent stress urinary
      incontinence.

PMID- 18613783
TI  - Determining the appropriate length of a double-pigtail ureteral stent by both
      stent configurations and related symptoms.
AB  - PURPOSE: To evaluate whether stent length affects the symptoms after stent
      insertion and to determine the appropriate stent length according to the stent
      configurations and the related symptoms simultaneously. PATIENTS AND METHODS: A
      total of 87 patients who underwent ureteroscopic lithotripsy (URSL) and double
      pigtail ureteral stent (22, 24, or 26 cm) insertion were enrolled. The stent
      configurations on the images were reviewed to determine whether the length was
      appropriate. All patients completed a questionnaire to assess the symptoms
      related to stent insertion. The incidence and severity of the symptoms were
      compared among the patients with different stent lengths. RESULTS: The
      demographic data were similar among the three groups with different stent lengths
      (22, 24, or 26 cm). The stent length was associated with the position of the
      distal loop (P = 0.02), while it was not associated with the position of the
      proximal loop (P = 0.50). The use of a longer stent was significantly associated
      with a higher incidence of urinary frequency (P = 0.04) and urgency (P = 0.02).
      Also, the use of a longer stent was also significantly associated with higher
      symptom scores of urinary frequency (P < 0.01) and urgency (P < 0.01).
      CONCLUSIONS: The stent length is associated with the position of the distal loop
      and the related urinary symptoms. A longer stent causes an overlong intravesical
      segment and more irritative symptoms. On the other hand, the stent length is not
      associated with either the position of the proximal loop or flank pain. Based on
      the analysis of both stent configurations on images and related symptoms, a 22-cm
      stent is more appropriate for those whose height ranges from 149.5 cm to 178.5 cm
      with a median of 161.9 cm.

PMID- 18613784
TI  - Impact of obesity on clinicopathologic outcomes after robot-assisted laparoscopic
      prostatectomy.
AB  - PURPOSE: To investigate the impact of body mass index (BMI) on pathologic and
      functional outcomes after robot-assisted laparoscopic prostatectomy (RALP).
      PATIENTS AND METHODS: We evaluated 400 consecutive patients who underwent RALP at
      the Mayo Clinic between 2002 and 2006. Patients were categorized as normal weight
      (BMI <25 kg/ m(2), n = 94), overweight (BMI 25-29.9 kg/m(2), n = 187), and obese
      (BMI >or=30 kg/m(2), n = 119). Clinicopathologic features of the groups were
      compared, and logistical regression analysis was used to assess the associations
      of BMI with pathologic and functional outcomes after RALP. RESULTS: Overweight
      and obese patients were more likely to have pT(3/4) disease (P = 0.0024) and
      pathologic Gleason 7 to 10 cancers (P < 0.0001). Overall, 9/94 (9.6%) normal
      weight patients had a positive surgical margin (SM), compared with 25/187 (13.4%)
      overweight patients and 21/119 (17.6%) obese men (P = 0.087). On multivariate
      analysis, however, increasing BMI was not significantly associated with an
      increased risk of positive SM (odds ratio 1.12, 95% confidence interval 0.72
      1.76, P = 0.61). In addition, although obese men had longer operative times (P =
      0.049) and greater intraoperative blood loss (P = 0.04), we found no association
      between BMI and transfusion requirement (P = 0.34), length of hospital stay (P =
      0.54), or the rates of early (P = 0.37) or late (P = 0.86) complications.
      Moreover, in those patients with follow-up available at 1 year after RALP,
      obesity did not impact the return of continence (P = 0.62) or potency (P = 0.13).
      CONCLUSION: BMI was not an independent predictor of positive SM, complications,
      incontinence, or erectile dysfunction after RALP. These data suggest that RALP
      may offer equivalent margin rates and functional outcomes for patients across
      BMI.

PMID- 18613785
TI  - Is endoscopic management suitable for long ureteral fibroepithelial polyps?
AB  - BACKGROUND AND PURPOSE: Fibroepithelial polyps of the ureter are rare benign
      tumors that have traditionally been managed by open exploration and resection.
      Endoscopic resection have been regarded as the gold standard for small lesions,
      while the management modality for long lesions is still controversial. We review
      our experience with ureteroscopic management of long (>6 cm) ureteral
      fibroepithelial polyps by holmium: yttrium-aluminum-garnet (YAG) laser resection.
      PATIENTS AND METHODS: Five patients with a long ureteral fibroepithelial polyp
      underwent ureteroscopic resection using a holmium:YAG laser. RESULTS: Endoscopic
      management was successful in all five patients, and no major complications
      resulted from the approach. The average length of stay was 3 days (range 2-5 d).
      The mean length of the lesions were 11 cm (range 6-16 cm). The ureteral stent was
      removed at 6 weeks. No recurrences were seen during a mean followup of 24.2
      months (range 3-51 mos). One ureteral stricture developed at 3 months, and the
      patient underwent endoscopic treatment by holmium:YAG laser. CONCLUSIONS:
      Endoscopic management of long ureteral fibroepithelial polyps is an acceptable
      modality with minimal morbidity and durable treatment results. The holmium:YAG
      laser offers the advantages of facilitating the use of a small-caliber fiber or
      flexible ureteroscope and allows safe destruction of the stalk and efficient
      removal of the entire polyp.

PMID- 18613786
TI  - Robotic laparoscopic radical prostatectomy for biopsy Gleason 8 to 10: prediction
      of favorable pathologic outcome with preoperative parameters.
AB  - PURPOSE: We sought to evaluate the pathologic results and postoperative outcomes
      for men undergoing robot-assisted laparoscopic radical prostatectomy (RLRP) for
      biopsy Gleason score (GS) 8 to 10 disease. Stratification of these patients
      according to preoperative variables was also performed in an attempt to predict
      organ-confined cancer. PATIENTS AND METHODS: A prospective RLRP database
      identified all patients with preoperative biopsy GS 8 to 10. Variables, including
      prostate-specific antigen (PSA), percent positive biopsy cores (%PBC), maximal
      percentage of cancer in biopsy core (%MCB), clinical stage, pathologic stage,
      pathologic GS, surgical margins status, lymph node status, time to biochemical
      recurrence, and recurrence rate, were evaluated. Preoperative variables were
      treated as continuous and categorical using PSA, %PBC and %MCB cutoffs of 10
      ng/mL, 50%, and 30%, respectively. RESULTS: Between February 2003 and September
      2007, a total of 1225 RLRPs were performed at the University of Chicago Medical
      Center. Seventy-two (5.9%) patients had preoperative biopsy GS 8 to 10. Two
      patients received neoadjuvant hormonal therapy and were excluded. Among 70
      patients evaluated, 33 (47%) had organconfined (pT(2)N0) disease. Forty (60.6%)
      patients had pathologic downgrading to GS <or=7. Overall positive surgical margin
      (PSM) rate was found to be 24.2%. pT(2)- and pT(3)-PSM rate was 6% and 42.3%,
      respectively. In multivariate logistic regression analysis, PSA <or=10 ng/mL (P =
      0.04) and %MCB <or=30% (P = 0.001) were found to be statistically significant
      predictors of pT(2)N0 disease. CONCLUSION: Preoperative biopsy GS 8 to 10
      predicts a significant likelihood of finding non-organ-confined prostate cancer
      on the final pathology report. Preoperative PSA <or=10 ng/mL and %MCB <or=30% may
      be used to predict favorable pathologic outcome for these patients during
      surgical counseling.

PMID- 18613787
TI  - Cystoscopic management of an extruded coil from arteriovenous fistula
      embolization using arthroscopic instruments.
AB  - Pelvic arteriovenous malformation (AVM) is a rare condition in which a section of
      blood vessels lacks a capillary network, resulting in blood from an artery being
      delivered directly to a vein. This condition may be congenital or acquired.
      Percutaneous selective embolization can obliterate AVMs and has increasingly been
      used for management. Management involves transcatheter embolization with either
      inert glues, balloons, or fibered titanium coils that are designed to limit the
      flow through feeding vessels. We describe one potential complication of
      transcatheter embolization that involves necrosis of the bladder wall with a
      novel technique for endoscopic management of an extruded coil in the bladder.

PMID- 18613788
TI  - Nomenclature of robotic procedures in urology.
AB  - PURPOSE: To standardize nomenclature and acronyms applied to robotic procedures
      in urology. MATERIALS AND METHODS: A review of the literature for robotic
      procedures in urology was performed. In addition, various acronyms were queried
      and frequency of use was noted. Additional literature reviewed included articles
      on standardization of scientific nomenclature used in other disciplines of health
      care. This topic was discussed within the newly formed working group of urologic
      robotic surgeons (WURS). RESULTS: There is wide variation in the terminology and
      use of acronyms for robotic prostate and kidney procedures. The application of
      robotic, robot, robotic laparoscopic, robot laparoscopic, robotic-assisted, robot
      assisted, robotic assisted, robot assisted, robotic-assisted laparoscopic, robot
      assisted laparoscopic, robotic assisted laparoscopic, robot assisted
      laparoscopic, and robotic computer-assisted to procedures such as pyeloplasty and
      radical prostatectomy is far from uniform or standardized. Queries and searches
      using acronyms such as RALP, RARP, RRP, and RP yielded publications discussing
      both prostate and renal procedures applying the same acronyms. There are
      established databases of abbreviations and acronyms, including ARGH, SaRad,
      Acromed, and the Stanford Biomedical Abbreviation Server. CONCLUSION:
      Standardization of the nomenclature applied to urologic robotic surgery is needed
      as the robotic literature continues to grow. The recommendation from the
      Scientific Committee of the Working Group of Urologic Robotic Surgeons is to
      apply "robot assisted" to the already established nomenclature currently used to
      describe equivalent open procedures. The use of standardized and uniform
      terminology for procedures performed with robots will facilitate literature
      search and research efforts in the future. The role of standardized nomenclature
      for billing purposes remains to be seen.

PMID- 18613789
TI  - Commonalities in sickness and in health.

PMID- 18613790
TI  - Detection of altered global DNA methylation in coronary artery disease patients.
AB  - Epigenetic modifications, especially alteration in DNA methylation, are
      increasingly being recognized as a key factor in the pathogenesis of complex
      disorders, including atherosclerosis. However, there are limited data on the
      epigenetic changes in the coronary artery disease (CAD) patients. In the present
      study we evaluated the methylation status of genomic DNA from peripheral
      lymphocytes in a cohort of 287 individuals: 137 angiographically confirmed CAD
      patients and 150 controls. The differential susceptibility of genomic DNA to
      methylation-sensitive restriction enzymes was utilized to assess the methylation
      status of the genome. We observed that the genomic DNA methylation in CAD
      patients is significantly higher than in controls (p < 0.05). Since elevated
      homocysteine levels are known to be an independent risk factor for CAD and a key
      modulator of macromolecular methylation, we investigated the probable correlation
      between plasma homocysteine levels and global DNA methylation. We observed a
      significant positive correlation of global DNA methylation with plasma
      homocysteine levels in CAD patients (p = 0.001). Further, within a higher range
      of serum homocysteine levels (>/=12-50 muM), global DNA methylation was
      significantly higher in CAD patients than in controls. The alteration in genomic
      DNA methylation associated with cardiovascular disease per se appears to be
      further accentuated by higher homocysteine levels.

PMID- 18613791
TI  - Myocyte-specific M-CAT and MEF-1 elements regulate G-protein gamma 3 gene
      (gamma3) expression in cardiac myocytes.
AB  - Little is known regarding the mechanisms that control the expression of G-protein
      alpha, beta, and gamma subtypes. We have previously shown that the G-protein
      gamma(3) gene is expressed in the heart, brain, lung, spleen, kidney, muscle, and
      testis in mice. We have also reported that the G-protein gamma(3) subunit is
      expressed in rat cardiac myocytes, but not in cardiac fibroblasts. Other studies
      have shown that the gamma(3) subunit couples to the angiotensin A1A receptor in
      portal vein myocytes, and has been shown to mediate beta-adrenergic
      desensitization in cardiac myocytes treated with atorvastatin. In the present
      study, we evaluated G-protein gamma(3) promoter-luciferase reporter constructs in
      primary myocytes to identify key regulatory promoter regions. We identified two
      important regions of the promoter (upstream promoter region [UPR] and downstream
      promoter region [DPR]), which are required for expression in cardiac myocytes. We
      observed that removal of 48 bp in the UPR diminished gene transcription by 75%,
      and that the UPR contains consensus elements for myocyte-specific M-CAT and
      myocyte enhancer factor 1 (MEF-1) elements. The UPR and DPR share transcription
      factor elements for myocyte-specific M-CAT element. We observed that cardiac
      myocyte proteins bind to gamma(3) oligonucleotides containing transcription
      factor elements for myocyte-specific M-CAT and MEF-1. Myocyte-specific M-CAT
      proteins were supershifted with transcriptional enhancer factor-1 (TEF-1)
      antibodies binding to the gamma(3) M-CAT element, which is in agreement with
      reports showing that the M-CAT element binds the TEF-1 family of transcription
      factors. The 150 bp DPR contains three M-CAT elements, an INR element, an
      upstream stimulatory factor 1 element, and the transcription start site. We have
      shown that myocyte gamma(3) gene expression is regulated by myocyte-specific M
      CAT and MEF-1 elements.

PMID- 18613792
TI  - Generation and characterization of an attenuated mutant in a response regulator
      gene of Francisella tularensis live vaccine strain (LVS).
AB  - Francisella tularensis is a zoonotic bacterium that must exist in diverse
      environments ranging from arthropod vectors to mammalian hosts. To better
      understand how virulence genes are regulated in these different environments, a
      transcriptional response regulator gene (genome locus FTL0552) was deleted in F.
      tularensis live vaccine strain (LVS). The FTL0552 deletion mutant exhibited
      slightly reduced rates of extracellular growth but was unable to replicate or
      survive in mouse macrophages and was avirulent in the mouse model using either
      BALB/c or C57BL/6 mice. Mice infected with the FTL0552 mutant produced reduced
      levels of inflammatory cytokines, exhibited reduced histopathology, and cleared
      the bacteria quicker than mice infected with LVS. Mice that survived infection
      with the FTL0552 mutant were afforded partial protection when challenged with a
      lethal dose of the virulent SchuS4 strain (4 of 10 survivors, day 21
      postinfection) when compared to naive mice (0 of 10 survivors by day 7
      postinfection). Microarray experiments indicate that 148 genes are regulated by
      FTL0552. Most of the genes are downregulated, indicating that FTL0552 controls
      transcription of genes in a positive manner. Genes regulated by FTL0552 include
      genes located within the Francisella pathogenicity island that are essential for
      intracellular survival and virulence of F. tularensis. Further, a mutant in
      FTL0552 or the comparable locus in SchuS4 (FTT1557c) may be an alternative
      candidate vaccine for tularemia.

PMID- 18613793
TI  - Thymosin alpha1- and ulinastatin-based immunomodulatory strategy for sepsis
      arising from intra-abdominal infection due to carbapenem-resistant bacteria.
AB  - OBJECTIVE: The aim of this study was to evaluate the potential efficacy of
      therapy with thymosin alpha(1) and ulinastatin for patients with sepsis due to
      carbapenem-resistant bacteria. DESIGN: Prospective, randomized, parallel
      controlled clinical study. METHODS: A total of 120 patients received a diagnosis
      of sepsis caused by infection with carbapenem-resistant bacteria and satisfied
      the study enrollment criteria. Sixty patients received carbapenems combined with
      thymosin alpha(1) and ulinastatin (the CTU group), and the other 60 patients were
      treated with carbapenems and placebo (the CP group). For both groups, flow
      cytometry was used to enumerate lymphocyte subsets, and ELISA was used to
      determine cytokine concentrations. RESULTS: When the 2 groups were compared, the
      CTU group exhibited a better performance with respect to organ failure scores
      such as the Acute Physiology and Chronic Health Evaluation II score, the Multiple
      Organ Failure Score, and the Glasgow Coma Scale. The CTU group also showed
      significant improvements in CD4(+)CD8(+) count after initiation of treatment. In
      addition, compared with the CP group, in the CTU group the balance between
      proinflammatory mediators (such as tumor necrosis factor-alpha, interleukin [IL]
      1beta, IL-6, and IL-8) and anti-inflammatory cytokines (including IL-4 and IL-10)
      was better modulated, and the cumulative survival rate of the CTU group exceeded
      that of the CP group by 17.8% at day 28, 25.9% at day 60, and 27.4% at day 90.
      CONCLUSION: Immunomodulatory therapy that combines thymosin alpha(1) and
      ulinastatin appears to improve the survival rate for patients infected with
      carbapenem-resistant bacteria. The number of patients in this study was
      relatively small, and although the same number of patients was initially enrolled
      in each study group, the groups were not the same size at the end of the study.
      Therefore, a larger clinical trial should be conducted to validate this
      conclusion. TRIAL REGISTRATION: The trial was registered with the Chinese State
      Food and Drug Administration (Peking Science and Technology Development Plan,
      2002[641]), (registration number 2007Y0211).

PMID- 18613794
TI  - Vaccination with clumping factor A and fibronectin binding protein A to prevent
      Staphylococcus aureus infection of an aortic patch in mice.
AB  - Staphylococcus aureus is a leading cause of ventricular assist device-related
      infections. This study evaluated the protective effect against S. aureus
      infection of active and passive immunization that targeted 3 proteins involved in
      bacterial attachment to a murine intra-aortic polyurethane patch. Active
      immunization of mice with a combination of the A domains of clumping factor A
      (ClfA), fibronectin-binding protein A (FnBPA) and fibronectin-binding protein B
      or passive immunization with monoclonal antibodies against ClfA and FnBPA
      resulted in a higher level of protection than that obtained by vaccination with
      either protein or antibody alone. The combination of antibodies or protein
      antigens appears to provide enhanced protection against prosthetic-device
      infection.

PMID- 18613795
TI  - Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism
      for the pathogenesis of avian influenza H5N1 infection.
AB  - The mechanism for the pathogenesis of H5N1 infection in humans remains unclear.
      This study reveals that cyclooxygenase-2 (COX-2) was strongly induced in H5N1
      infected macrophages in vitro and in epithelial cells of lung tissue samples
      obtained during autopsy of patients who died of H5N1 disease. Novel findings
      demonstrated that COX-2, along with tumor necrosis factor alpha and other
      proinflammatory cytokines were hyperinduced in epithelial cells by secretory
      factors from H5N1-infected macrophages in vitro. This amplification of the
      proinflammatory response is rapid, and the effects elicited by the H5N1-triggered
      proinflammatory cascade are broader than those arising from direct viral
      infection. Furthermore, selective COX-2 inhibitors suppress the hyperinduction of
      cytokines in the proinflammatory cascade, indicating a regulatory role for COX-2
      in the H5N1-hyperinduced host proinflammatory cascade. These data provide a basis
      for the possible development of novel therapeutic interventions for the treatment
      of H5N1 disease, as adjuncts to antiviral drugs.

PMID- 18613797
TI  - The root cause of patient safety concerns in an Internet pharmacy.
AB  - BACKGROUND: The Internet has become a revolutionary technology that affords
      worldwide opportunities never seen before. One such opportunity is the purchase
      of drugs over the Internet and the business of Internet pharmacies which has
      become prolific. Associated with this proliferation is the concern for patient
      safety. Numerous studies have shown that drugs purchased over the Internet come
      from pharmacies in a country other than the one where the patient resides and
      these pharmacies are not licensed, sometimes provide drugs without a prescription
      and that are not of the same composition as they should be, and do not provide
      adequate directions to the patient. In addition, the packaging of the drugs may
      be compromised resulting in altered medication. OBJECTIVE: This paper examines
      the root cause of patient safety issues in Internet pharmacies. METHODS: A review
      of the literature including the marketing literature was conducted.
      RESULTS/CONCLUSION: Healthcare marketing concepts guide business owners to
      identify patients' wants and distinguish them from their needs. Marketing
      principles detail aggressive marketing strategies within an organization's
      mission and in an ethical manner. Some Internet pharmacies misinterpret proven
      marketing principles and become overly aggressive in the market place focusing
      only on sales and profit rather than focusing on patient safety and long-term
      success of the Internet pharmacy.

PMID- 18613798
TI  - The FDA Drug Safety Bill: how safe are our drugs?
AB  - The world of drug safety is undergoing major changes in the US, Europe and
      elsewhere following several major drug withdrawals, billion dollar lawsuits, NGO
      studies of drug safety and widespread media attention in the US. Some of the
      events of the past few years are reviewed along with some of the reactions and
      changes in the FDA and the field of drug safety followed by the author's
      conclusions and views on the future of drug safety.

PMID- 18613799
TI  - Drug allergies--unknown dangers to patients.
AB  - BACKGROUND: Drug hypersensitivity reactions are unpredictable side effects. They
      are a frequent worry for clinicians of all disciplines. Available clinical and
      pathological data are scarce, as are diagnosis centers. OBJECTIVE: To review the
      unmet needs in drug hypersensitivity clinical and basic research. METHODS: A
      literature search was performed and expert opinions in the field were collected.
      RESULTS/CONCLUSION: Drug hypersensitivity reactions are not so rare adverse
      events. The mechanisms are multiple and a firm diagnosis is often possible.
      However, further research is needed.

PMID- 18613800
TI  - Investigations into the liver effects of ximelagatran using high content
      screening of primary human hepatocyte cultures.
AB  - BACKGROUND: Ximelagatran, the first oral agent in the new class of direct
      thrombin inhibitors, was withdrawn from the market due to increased rates of
      liver enzyme elevations in long-term treatments. Despite intensive pre clinical
      investigations the cellular mechanisms behind the observed hepatic effects remain
      unknown. OBJECTIVE: The aim of this study was to assess drug-induced cytotoxicity
      in primary human hepatocyte cultures by ximelagatran and other reference
      pharmaceutical agents with known in vivo hepatotoxic profiles. METHODS: Drugs
      cause liver injury by many distinct mechanisms that result in abnormal cellular
      functioning and different patterns of injury. To address many potential toxic
      mechanisms in a human-relevant model, freshly isolated human hepatocytes were
      used in automated imaging assays. Ximelagatran was used as a test compound to
      study biochemical and morphological changes in human hepatocytes. In addition, 11
      control, reference and comparator compounds with known liver-toxic potential in
      humans were used. The response to these compounds was assessed across five
      different hepatocyte donor preparations. RESULTS: Cytotoxicity induced by a
      number of compounds was quantitatively monitored using an automated imaging
      technique. A variety of morphological changes in hepatocyte cytoskeleton and
      mitochondrial function could be identified at sublethal doses of test compounds.
      Doses of ximelagatran up to 500 microM did not cause a cytotoxic response in the
      majority of preparations and no subcytotoxic response was observed at doses below
      125 microM. CONCLUSIONS: The experiments described here demonstrate that primary
      human hepatocytes may be used in a medium-throughput format for screening using
      imaging-based assays for the identification of cellular responses. Overall, it is
      concluded that ximelagatran did not cause a significant decrease in cell
      viability when incubated for 24 h at considerably higher concentrations than are
      found in plasma following therapeutic dosing.

PMID- 18613801
TI  - The cardiovascular safety of rosiglitazone.
AB  - BACKGROUND: Thiazolidinediones (rosiglitazone, pioglitazone) influence insulin
      sensitivity and are used for the treatment of Type 2 diabetes. Rosiglitazone
      achieves sustained improvements in glycaemic control, whilst having pleiotropic
      effects on cardiovascular risk factors. However, analysis of cardiovascular
      outcomes has been controversial. OBJECTIVES: Review the cardiovascular safety of
      rosiglitazone by conducting a literature search. METHODS: We conducted a PubMed
      search and critically reviewed published work on cardiovascular outcome of
      rosiglitazone, including clinical studies and meta-analyses. RESULTS/CONCLUSION:
      The meta-analysis by Nissen and Wolski suggested increased cardiovascular risk in
      users of rosiglitazone, but this was not supported by an interim analysis of the
      RECORD trial designed to evaluate this, and several other reports failed to shed
      conclusive light on this issue. The cardiovascular benefits of pioglitazone have
      also been in doubt due to the failure of the PROactive trial to reach the primary
      cardiovascular end points, although this study reported a significant reduction
      in secondary end points. All of this has left diabetes care in some disarray,
      with weak evidence for adverse cardiovascular effects driving the reduced use of
      rosiglitazone, an agent that has important sustained effects on glycaemic
      control.

PMID- 18613802
TI  - The safety of cefepime in the treatment of infection.
AB  - BACKGROUND: Cefepime is a fourth-generation cephalosporin usually reserved for
      treating severe nosocomial pneumonia, as well as empirical treatment of febrile
      neutropenia, uncomplicated and complicated urinary tract infections,
      uncomplicated skin and skin structure infections, and complicated intra-abdominal
      infections. OBJECTIVE: Since reports of neurotoxic effects and of an all-cause
      mortality higher with cefepime than with comparators have created some concerns
      regarding its safety, this paper reviews data available in the PubMed database up
      to December 2007 on cefepime safety. METHODS: Literature data from PubMed
      obtained by combining cefepime and safety, or cefepime and clinical trials, were
      examined. RESULTS/CONCLUSIONS: Caution in the use of cefepime should be adopted
      until new evidence on cefepime safety is available.

PMID- 18613803
TI  - Nephrotoxicity associated with antiretroviral therapy in HIV-infected patients.
AB  - BACKGROUND: With the success of modern antiretroviral therapies in increasing
      longevity of patients with HIV infection, chronic conditions including renal
      disease have assumed a greater importance in patient management. Some
      antiretroviral therapies have themselves been identified to have clinically
      significant nephrotoxicity. OBJECTIVE: To review the risk factors and mechanisms
      for renal toxicity of antiretroviral drugs, and their impact on the clinical
      management of patients with HIV. METHODS: Current literature and HIV treatment
      guidelines are reviewed. RESULTS/CONCLUSIONS: Background rates of renal disease
      and associated risk factors are significant in the HIV clinic population, and
      renal function should be assessed in all HIV-infected patients. Modern HIV
      treatment regimens have a relatively low but clinically significant nephrotoxic
      potential; therefore, renal function should be evaluated on an ongoing basis in
      patients receiving antiretroviral therapy.

PMID- 18613804
TI  - The safety of celecoxib in ankylosing spondylitis treatment.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) play a crucial role in
      the treatment of ankylosing spondylitis (AS). Most of the AS patients require a
      continuous and long-term NSAIDs therapy; therefore the question of NSAIDs safety
      in this population becomes very important. OBJECTIVE: to review the safety of
      celecoxib in ankylosing spondylitis treatment. METHODS: The PubMed database was
      searched using the keywords 'ankylosing spondylitis' and 'celecoxib', with the
      following extraction of clinical trials investigating efficacy and safety of
      celecoxib in AS. RESULTS/CONCLUSIONS: Four clinical trials were found: three
      randomized controlled trials (RCTs) and one open-label extension of a previous
      RCT. All RCTs showed a good safety profile for celecoxib treatment in AS, similar
      to that of nonselective NSAIDs. However, long-term (>or= 1 year) celecoxib safety
      in AS was not investigated in RCTs. Based on the results of long-term non-AS
      celecoxib studies, most of the AS patients (because of young age and fewer
      comorbidities) are probably at low risk for cardiovascular and gastrointestinal
      complications. Celecoxib showed a good efficacy and safety profile in AS, but
      further investigations are needed to clarify the long-term safety of celecoxib in
      this group of patients.

PMID- 18613805
TI  - Efficacy and safety of TNF-blocker therapy in systemic lupus erythematosus.
AB  - BACKGROUND: There is still unmet medical need in the therapy of severe organ
      manifestations of patients with systemic lupus erythematosus (SLE). Therapeutic
      agents targeting pro-inflammatory cytokines may be an interesting option.
      OBJECTIVE: To review available data on the efficacy and safety of tumour necrosis
      factor (TNF) blockade in SLE. METHODS: A review of the literature was conducted.
      RESULTS/CONCLUSIONS: Open-label experience suggests that TNF blockade is
      effective in SLE patients with arthritis, nephritis and skin disease. In
      particular, nephritis may remain in long-term remission after just four infusions
      of infliximab administered. Despite the induction of lupus-specific
      autoantibodies, short-term therapy with infliximab in combination with
      azathioprine appears feasible and relatively safe. The data call for controlled
      clinical trials, at least one of which has been initiated.

PMID- 18613806
TI  - Activity of certain drugs in inducing of inflammatory myopathies with cutaneous
      manifestations.
AB  - BACKGROUND: At present, the pharmacological activity of drugs in inducing of
      inflammatory myopathies is not a solved problem. OBJECTIVE: Analysis of the
      adverse reaction of drugs show that in both adults and children they can cause
      clinical manifestations of dermatomyositis and its variants [classic, juvenile,
      paraneoplastic or amyopathic], polymyositis and its variants [eosinophilic
      myositis, overalp syndrome], or other conditions such as eosinophilia myalgia
      syndrome, and eosinophilic fasciitis. METHODS: Literature databases were analyzed
      and combined with personal experience to identify drug activity associated with
      dermatomyositis and its variants. CONCLUSION: Lipid-lowering agents, anti
      infectious, NSAIDs, antineoplastic medicines, other non-related drugs, vaccines,
      and over the counter essential amino acids such as L-tryptophan are of particular
      interest in the induction of myositis, or myalgia and cutaneous features of
      idiopathic inflammatory myopathies. Clinical manifestations and various
      pathogenetic mechanisms leading to injury of muscles and skin from medicines in
      this illness are presented and analyzed.

PMID- 18613807
TI  - Safety and efficacy of psychopharmacological agents used to treat the psychiatric
      sequelae of common neurological disorders.
AB  - BACKGROUND: Psychiatric disorders and symptoms, ranging from mood dysregulation
      to delirium, are commonly observed in many neurological disorders. These
      manifestations complicate the illness and worsen prognosis. Pharmacological
      treatment options may be limited by the primary neurological illness and side
      effects. OBJECTIVE: This paper aims to review the safety and efficacy of
      pharmacological agents used to treat psychiatric manifestations of several common
      neurological conditions, including Alzheimer's disease (AD), post-stroke,
      traumatic brain injury (TBI) and epilepsy. METHODS: Systematic review of the
      Medline database for articles published between 2000 and 2007 was done to
      retrieve relevant articles. RESULTS: The paucity of controlled data on the
      pharmacological treatments of psychiatric manifestations of neurological
      conditions makes recommendations difficult. CONCLUSION: When secondary
      depression, mania, anxiety, and delirium remain after treatment of the underlying
      condition, clinical experience and the limited research indicates that judicious
      pharmacological interventions may effectively treat mood dysregulation, delirium
      and agitation.

PMID- 18613808
TI  - Genotoxic effects of anesthetic agents.
AB  - BACKGROUND: Preliminary research results indicate that exposure to anesthetics
      affects health. OBJECTIVE: To provide, with evidence-based knowledge, the answer
      to the question: What are the genotoxic effects threatening people exposed to
      anesthetics? METHOD: A systematic review of scientific literature. A systematic
      search of The Cochrane Library, MedLine, and CINAHL resulted in a screening of
      212 abstracts of which 54 articles were assessed for quality. The 54 articles
      assessed covered areas on general health effects (neurobehavioral effects,
      immunology) and, in particular, genotoxic effects. RESULTS/CONCLUSION: In the
      scientific literature reviewed, there is evidence of exposure to anesthetics,
      especially nitrous oxide and halogenated gases, being associated with general
      health and genotoxic risks, but conflicting results have been obtained. The
      result of this review further stresses the need for scientific knowledge in this
      area and enhances the studies, above all, on people exposed for long periods.

PMID- 18613809
TI  - The safety of disulfiram for the treatment of alcohol and cocaine dependence in
      randomized clinical trials: guidance for clinical practice.
AB  - BACKGROUND: Disulfiram has demonstrated efficacy in six randomized clinical
      trials for the treatment of cocaine dependence, but is rarely used in clinical
      settings because of safety concerns. OBJECTIVE: What are the common and serious
      side effects of disulfiram in cocaine-dependent individuals with and without
      alcohol dependence in randomized clinical trials? METHODS: We located Phase I and
      II randomized trials that discussed the safety of disulfiram.
      RESULTS/CONCLUSIONS: In randomized clinical trials that eliminated subjects with
      serious cardiovascular, hepatic, and psychiatric disorders, the most frequent
      side effects of disulfiram over placebo or index groups include headaches,
      fatigue, sleepiness, and anxiety. Disulfiram in a dose of <or= 250 mg/day led to
      only mild interactions with alcohol. When patients are screened for medical and
      psychiatric stability, and are evaluated for drug interactions, disulfiram has an
      acceptable side-effect profile for the treatment of cocaine dependence with or
      without alcohol dependence.

PMID- 18613810
TI  - Safety of anticholinergics in patients with benign prostatic hyperplasia.
AB  - BACKGROUND: Storage lower urinary tract symptoms (LUTS) or overactive bladder
      (OAB) often coexist with voiding symptoms in patients with benign prostatic
      obstruction (BPO). Anticholinergic medications to treat storage LUTS are often
      withheld in such patients for fear of significantly increasing post-void residual
      urine volumes or provoking acute urinary retention (AUR). OBJECTIVE: To assess
      the clinical validity of concerns regarding urinary safety of anticholinergics in
      patients with benign prostatic hyperplasia. METHODS: Review of indexed literature
      and congress abstracts. RESULTS/CONCLUSIONS: Existing urinary and non-urinary
      safety data on BPO patients administered anticholinergics, either alone or in
      combination with alpha-blockers, do not seem to support the above-mentioned
      concerns. Nevertheless, precise criteria for patient and drug selection to
      ascertain safe and effective administration are not yet established and need to
      be investigated in future trials.

PMID- 18613811
TI  - Recognition and management of drug-induced blood cytopenias: the example of drug
      induced acute neutropenia and agranulocytosis.
AB  - BACKGROUND: More than several hundred drugs, toxins, and herbs have been reported
      to cause blood abnormalities, and drugs account for 20 - 40% of all instances of
      cytopenias. OBJECTIVE: In the present paper, we report and discuss the
      recognition and the management of drug-induced acute neutropenia or
      agranulocytosis (neutrophil count of < 0.5 x 10(9)/l). METHODS: A bibliographic
      search was performed on the PubMed database of the US National Library of
      Medicine for articles published from January 1990 to January 2008. Additional not
      published data of our cohort of drug-induced agranulocytosis in the University
      Hospital of Strasbourg, France were incorporated in this review.
      RESULTS/CONCLUSIONS: Idiosyncratic drug-induced acute neutropenia or
      agranulocytosis is a serious adverse event due to the frequency of severe
      infections (such as deep infections, septicemia and septic shock) but modern
      management with broad spectrum antibiotics and hematopoietic growth factors is
      likely to improve the prognosis. Given the increased life expectancy, increasing
      use of medications as a therapeutic modality and subsequent longer exposure to
      drugs, as well as the development of new agents, healthcare professionals should
      be aware of this adverse event and its management.

PMID- 18613812
TI  - Insight into bisphosphonate-associated osteomyelitis of the jaw: pathophysiology,
      mechanisms and clinical management.
AB  - BACKGROUND: Bisphosphonates are widely used for the treatment of bone diseases.
      Bisphosphonate-associated osteomyelitis of the jaw (BAOMJ) affects 1 per 100,000
      patients-treated years for non-cancer bone diseases and approximately 1 - 2% of
      cancer patients treated with bisphosphonates. RESULTS: The mechanism of
      sustaining osteonecrosis of the jaw (ONJ) is unclear, but several predisposing
      factors have been identified. The dosage, frequency of administration and the
      duration of bisphosphonate therapy may precipitate BAOMJ. CONCLUSION: Evidence
      supports immune and infectious etiology for BAOMJ. Hence, the term BAOMJ seems
      more appropriate than ONJ or BAON (bisphosphonate-associated ONJ).
      Bisphosphonates are the mainstay of therapy for osteoporosis. Cancer patients
      receive 10 - 15 times higher doses of bisphosphonates at a greater frequency per
      year than osteoporosis patients. This may trigger BAOMJ in such patients. The
      benefits of bisphosphonate therapy outweigh the incidence and risks of BAOMJ.
      Bisphosphonates show a temporal association with BAOMJ and no direct causal
      relation with ONJ.

PMID- 18613813
TI  - CD95 ligation and intracellular membrane flow.
AB  - Whereas ligation of the CD95 death receptor in the plasma membrane of so-called
      type I cells leads to a direct caspase 8-dependent activation of downstream
      effector caspases, mitochondrial amplification of caspase 8-derived signals is
      required in so-called type II cells in order to execute apoptotic cell death. In
      type I cells CD95L (CD95 ligand) binding to CD95 results in a ceramide-dependent
      formation of the DISC (death-inducing signalling complex) and caspase 8-dependent
      CD95 clustering in the plasma membrane, followed by an internalization of these
      multimeric-receptor-DISC complexes. In contrast, in the hepatocyte, a type II
      cell, the bulk of CD95 is stored intracellularly under resting conditions and
      only a few 'sentinel' CD95 receptors are present in the plasma membrane. However,
      their activation by CD95L is sufficient to trigger a caspase 8-dependent
      endosomal acidification and a ceramide-dependent trafficking of intracellularly
      stored CD95 to the plasma membrane, thereby amplifying CD95 activation. Thus, in
      both type I and type II cells, ceramide and CD95 receptor endo- and exo-cytosis
      are involved in CD95-mediated apoptosis, but apparently in different ways. This,
      however, is not the only effect of CD95 ligation on intracellular membrane flow
      in type II cells, and evidence has been presented that soon after CD95 ligation
      Golgi elements intermix caspase-dependently with mitochondria. In this issue of
      the Biochemical Journal, Matarrese et al. report another aspect on endocytosis in
      response to CD95 ligation in type II cells, namely a caspase-independent
      endocytosis with vesicle translocation to the mitochondrial compartment,
      suggestive of an interplay between both organelles in the sense of an 'organelle
      scrambling'. Thus early effects of CD95 activation on intracellular membrane flow
      may be much more complex than previously thought, but much has still to be
      learned about signalling mechanisms and the role they play in apoptosis.

PMID- 18613814
TI  - Phosphorylation of Argonaute proteins: regulating gene regulators.
AB  - Members of the Ago (Argonaute) protein family are the mediators of small RNA
      guided gene-silencing pathways including RNAi (RNA interference), translational
      regulation by miRNAs (microRNAs) and transcriptional silencing. Recent findings
      by Zeng et al. in this issue of the Biochemical Journal demonstrate that Ago
      proteins are post-translationally modified by phosphorylation of Ser(387).
      Mutating Ser(387) to alanine leads to reduced localization of human Ago2 to
      cytoplasmic P-bodies (processing bodies), cellular sites where RNA turnover and,
      at least in part, miRNA-guided gene regulation occurs. Zeng et al. further show
      that a member of the MAPK (mitogen-activated protein kinase) signalling pathway
      phosphorylates Ago2 at Ser(387), suggesting that Ago2-mediated gene silencing
      might be linked to distinct signalling pathways.

PMID- 18613816
TI  - A role for actin in regulating apoptosis/programmed cell death: evidence spanning
      yeast, plants and animals.
AB  - Achieving an understanding of how apoptosis/PCD (programmed cell death) is
      integrated within cellular responses to environmental and intracellular signals
      is a daunting task. From the sensation of a stimulus to the point of no return, a
      programme of cell death must engage specific pro-death components, whose effects
      can in turn be enhanced or repressed by downstream regulatory factors. In recent
      years, considerable progress has been made in our understanding of how components
      involved in these processes function. We now know that some of the factors
      involved in PCD networks have ancient origins that pre-date multicellularity and,
      indeed, eukaryotes themselves. A subject attracting much attention is the role
      that the actin cytoskeleton, itself a cellular component with ancient origins,
      plays in cell death regulation. Actin, a key cellular component, has an
      established role as a cellular sensor, with reorganization and alterations in
      actin dynamics being a well known consequence of signalling. A range of studies
      have revealed that actin also plays a key role in apoptosis/PCD regulation.
      Evidence implicating actin as a regulator of eukaryotic cell death has emerged
      from studies from the Animal, Plant and Fungal Kingdoms. Here we review recent
      data that provide evidence for an active, functional role for actin in
      determining whether PCD is triggered and executed, and discuss these findings
      within the context of regulation of actin dynamics.

PMID- 18613817
TI  - Abstracts of the Association of Coloproctology of Great Britain and Ireland
      Annual Meeting. June 30-July 3, 2008. Birmingham, United Kingdom.

PMID- 18613826
TI  - A golden era of opportunity in immunotherapy discovery and development.

PMID- 18613815
TI  - Structure, mechanism and regulation of pyruvate carboxylase.
AB  - PC (pyruvate carboxylase) is a biotin-containing enzyme that catalyses the
      HCO(3)(-)- and MgATP-dependent carboxylation of pyruvate to form oxaloacetate.
      This is a very important anaplerotic reaction, replenishing oxaloacetate
      withdrawn from the tricarboxylic acid cycle for various pivotal biochemical
      pathways. PC is therefore considered as an enzyme that is crucial for
      intermediary metabolism, controlling fuel partitioning toward gluconeogenesis or
      lipogenesis and in insulin secretion. The enzyme was discovered in 1959 and over
      the last decade there has been much progress in understanding its structure and
      function. PC from most organisms is a tetrameric protein that is allosterically
      regulated by acetyl-CoA and aspartate. High-resolution crystal structures of the
      holoenzyme with various ligands bound have recently been determined, and have
      revealed details of the binding sites and the relative positions of the biotin
      carboxylase, carboxyltransferase and biotin carboxyl carrier domains, and also a
      unique allosteric effector domain. In the presence of the allosteric effector,
      acetyl-CoA, the biotin moiety transfers the carboxy group between the biotin
      carboxylase domain active site on one polypeptide chain and the
      carboxyltransferase active site on the adjacent antiparallel polypeptide chain.
      In addition, the bona fide role of PC in the non-gluconeogenic tissues has been
      studied using a combination of classical biochemistry and genetic approaches. The
      first cloning of the promoter of the PC gene in mammals and subsequent
      transcriptional studies reveal some key cognate transcription factors regulating
      tissue-specific expression. The present review summarizes these advances and also
      offers some prospects in terms of future directions for the study of this
      important enzyme.

PMID- 18613827
TI  - Role of cytokines in rheumatoid arthritis: an education in pathophysiology and
      therapeutics.
AB  - SUMMARY: Advances in cDNA and monoclonal antibody technology in the 1980s fuelled
      the discovery and characterization of the properties of cytokines. It became
      apparent that because cytokines were expressed in tissues derived from autoimmune
      diseases, they were likely to be of fundamental importance in disease
      pathogenesis and developing a new class of biological therapeutics. In this
      review, we describe the history of bench to bedside translation of work that led
      to the identification of tumor necrosis factor (TNF) as a key regulator of the
      loss of homeostatic immune-inflammatory responses in rheumatoid arthritis (RA)
      and a good therapeutic target. First in human clinical trials in collaboration
      with a biotechnology company, the safety and efficacy of TNF blockade with a
      chimeric monoclonal antibody was substantiated in patients refractory to standard
      anti-rheumatoid drugs. Abnormal immune-inflammatory responses after therapy
      showed improvement and remain a focus of ongoing research in many laboratories.
      Longer term multi-center studies that followed with several anti-TNF biologicals
      have demonstrated the augmented efficacy, including inducing clinical remission,
      of low dose methotrexate and anti-TNF therapy co-therapy, but serious infections
      and lymphomas in a low frequency have been observed. In the course of the past
      decades, three 'blockbuster' anti-TNF biologicals are in the clinic. Over a
      million patients with RA and other immune-mediated diseases have been
      successfully treated, and a better perspective on the risk of harm and its
      management has become part of good clinical practice. This success has encouraged
      a burgeoning industry of biologicals for chronic diseases.

PMID- 18613828
TI  - IL-1, IL-18, and IL-33 families of cytokines.
AB  - SUMMARY: The interleukin-1 (IL-1), IL-18, and IL-33 families of cytokines are
      related by mechanism of origin, receptor structure, and signal transduction
      pathways utilized. All three cytokines are synthesized as precursor molecules and
      cleaved by the enzyme caspase-1 before or during release from the cell. The NALP
      3 inflammasome is of crucial importance in generating active caspase-1. The IL-1
      family contains two agonists, IL-1alpha and IL-1beta, a specific inhibitor, IL-1
      receptor antagonist (IL-1Ra), and two receptors, the biologically active type IL
      1R and inactive type II IL-1R. Both IL-1RI and IL-33R utilize the same
      interacting accessory protein (IL-1RAcP). The balance between IL-1 and IL-1Ra is
      important in preventing disease in various organs, and excess production of IL-1
      has been implicated in many human diseases. The IL-18 family also contains a
      specific inhibitor, the IL-18-binding protein (IL-18BP), which binds IL-18 in the
      fluid phase. The IL-18 receptor is similar to the IL-1 receptor complex,
      including a single ligand-binding chain and a different interacting accessory
      protein. IL-18 provides an important link between the innate and adaptive immune
      responses. Newly described IL-33 binds to the orphan IL-1 family receptor T1/ST2
      and stimulates T-helper 2 responses as well as mast cells.

PMID- 18613830
TI  - The role of IL-21 in regulating B-cell function in health and disease.
AB  - SUMMARY: Interleukin-21 (IL-21) belongs to a family of cytokines that includes IL
      2, IL-4, IL-7, IL-9, and IL-15, all of which bind to private (or shared)
      receptors as well as the common cytokine receptor gamma-chain as a component.
      Most cytokines in this family are critically important for both the maintenance
      and function of T cells and B cells. The receptor for IL-21 is widely distributed
      on lymphohematopoietic cells, and IL-21 plays many biologic roles, including
      maintenance and function of CD8(+) memory T cells and natural killer cells, as
      well as promoting the generation of Th17 cells in the mouse. One principal non
      redundant role of IL-21 is the promotion of B-cell activation, differentiation or
      death during humoral immune responses. Furthermore, increased IL-21 production is
      characteristic of certain autoimmune diseases and is likely to contribute to
      autoantibody production as well as pathologic features of autoimmune disease. In
      contrast, IL-21 may function as a co-adjuvant to enhance antibody responses and
      thereby facilitate host defense to malignances and infectious diseases. The
      critical role of IL-21 in promoting humoral immune responses makes it an
      important focus of potential therapeutic interventions in conditions
      characterized by either overproduction of pathogenic autoantibodies or under
      production of protective antibodies.

PMID- 18613829
TI  - How the study of children with rheumatic diseases identified interferon-alpha and
      interleukin-1 as novel therapeutic targets.
AB  - SUMMARY: Our studies in children with rheumatic diseases have led to the
      identification of two of the oldest cytokines, type I interferon (IFN) and
      interleukin 1 (IL-1), as important pathogenic players in systemic lupus
      erythematosus (SLE) and systemic onset juvenile arthritis (SoJIA), respectively.
      These findings were obtained by studying the transcriptional profiles of patient
      blood cells and by assessing the biological and transcriptional effect(s) of
      active patient sera on healthy blood cells. We also identified a signature that
      can be used to promptly diagnose SoJIA from other febrile conditions. Finally,
      our pilot clinical trials using IL-1 blockers have shown remarkable clinical
      benefits in SoJIA patients refractory to other medications.

PMID- 18613832
TI  - Strategies for use of IL-10 or its antagonists in human disease.
AB  - SUMMARY: Interleukin-10 (IL-10) is a cytokine with broad anti-inflammatory
      properties by its suppression of both macrophage and dendritic cell function,
      including antigen-presenting cell function and the production of proinflammatory
      cytokines. This can result subsequently in the feedback regulation of both T
      helper 1 (Th1)-type and Th2-type responses. This review discusses the potential
      use of IL-10 or agents that induce IL-10 as potential anti-inflammatory therapies
      in inflammatory diseases. Although IL-10-deficient mice develop colitis in the
      presence of normal gut flora and clear certain intracellular pathogens more
      efficiently, this is often accompanied by immunopathology, which can be lethal to
      the host. This reinforces the anti-inflammatory properties of IL-10, although it
      should be noted that as discussed below, IL-10 can also promote B-cell and other
      immune responses under particular settings. A penalty of its role to limit the
      immune and inflammatory responses to pathogens and prevent damage to the host is
      that high or dysregulated levels of IL-10 may result in chronic infection. Thus,
      antagonists of IL-10 show great potential as adjuvants in preventative or
      therapeutic vaccines against chronic infection or cancer. This article reviews
      basic published studies on IL-10, which may lead to potential uses of IL-10 or
      its antagonists in human disease.

PMID- 18613831
TI  - Th17 cells in human disease.
AB  - SUMMARY: Our understanding of the role of T cells in human disease is undergoing
      revision as a result of the discovery of T-helper 17 (Th17) cells, a unique
      CD4(+) T-cell subset characterized by production of interleukin-17 (IL-17). IL-17
      is a highly inflammatory cytokine with robust effects on stromal cells in many
      tissues. Recent data in humans and mice suggest that Th17 cells play an important
      role in the pathogenesis of a diverse group of immune-mediated diseases,
      including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel
      disease, and asthma. Initial reports also propose a role for Th17 cells in
      tumorigenesis and transplant rejection. Important differences, as well as many
      similarities, are emerging when the biology of Th17 cells in the mouse is
      compared with corresponding phenomena in humans. As our understanding of human
      Th17 biology grows, the mechanisms underlying many diseases are becoming more
      apparent, resulting in a new appreciation for both previously known and more
      recently discovered cytokines, chemokines, and feedback mechanisms. Given the
      strong association between excessive Th17 activity and human disease, new
      therapeutic approaches targeting Th17 cells are highly promising, but the
      potential safety of such treatments may be limited by the role of these cells in
      normal host defenses against infection.

PMID- 18613833
TI  - Therapeutic targeting of Janus kinases.
AB  - SUMMARY: Cytokines play pivotal roles in immunity and inflammation, and targeting
      cytokines and their receptors is an effective means of treating such disorders.
      Type I and II cytokine receptors associate with Janus family kinases (JAKs) to
      effect intracellular signaling. These structurally unique protein kinases play
      essential and specific roles in immune cell development and function. One JAK,
      JAK3, has particularly selective functions. Mutations of this kinase underlie
      severe combined immunodeficiency, indicative of its critical role in the
      development and function of lymphocytes. Because JAK3 appears not to have
      functions outside of hematopoietic cells, this kinase has been viewed as an
      excellent therapeutic target for the development of a new class of
      immunosuppressive drugs. In fact, several companies are developing JAK3
      inhibitors, and Phase II studies are underway. Mutations of Tyk2 cause autosomal
      recessive hyperIgE syndrome, and in principle, Tyk2 inhibitors might also be
      useful as immunosuppressive drugs. JAK2 gain-of-function mutations (V617F)
      underlie a subset of disorders collectively referred to as myeloproliferative
      diseases and phase 2 trials using JAK inhibitors are underway in this setting.
      Thus, we are learning a great deal about the feasibility and effectiveness of
      targeting Janus kinases, and it appears likely that this will be a fruitful
      strategy in a variety of settings.

PMID- 18613834
TI  - CTLA-4: a key regulatory point in the control of autoimmune disease.
AB  - SUMMARY: Chronic autoimmune disease in humans is the result of a failure to
      control autoreactive immune cells in the periphery. This control is largely
      achieved by inhibition of newly activated and memory cells. A number of negative
      immune regulatory pathways have been characterized. The cell surface coreceptor
      cytotoxic T-lymphocyte antigen-4 (CTLA-4) has emerged as a critical attenuator of
      T-cell activation and an essential component of the regulatory systems that serve
      to maintain peripheral tolerance. CTLA-4 expression is induced on the surface of
      T cells after they have received a costimulatory signal from antigen-presenting
      cells (APCs) via engagement of CD28 on the T-cell surface. CTLA-4 attenuates this
      costimulation by competing for CD28 ligands and through direct effects on APCs
      via the same ligands utilized by CD28. A large number of genetic association
      studies suggest that the CTLA-4 gene is a locus of susceptibility to autoimmune
      disease. However, specific functional defects in the CTLA-4 gene in patients have
      not been identified to date. Elucidating the role of CTLA-4 in immune tolerance
      has also led to a number of therapeutic applications, particularly in the
      treatment of malignancy and autoimmune disease.

PMID- 18613835
TI  - BAFF blockade for systemic lupus erythematosus: will the promise be fulfilled?
AB  - SUMMARY: Systemic lupus erythematosus (SLE) is a complex immune disorder in which
      loss of tolerance to nucleic acid antigens and other cross-reactive antigens is
      associated with the development of pathogenic autoantibodies that damage target
      organs including the skin, joints, brain, and kidney. B cells are essential to
      lupus pathogenesis, not only because they produce pathogenic autoantibodies but
      also because they have multiple effector functions in the immune system. There
      has been much recent interest therefore in targeting of B cells for the treatment
      of SLE and other autoimmune diseases. BAFF (B-cell activation factor belonging to
      the tumor necrosis factor family) is a crucial homeostatic cytokine for B cells
      that is upregulated during inflammation and links adaptive with innate immunity.
      Excessive levels of BAFF may alter selection of autoreactive B cells and
      contribute to perpetuation of SLE by a variety of mechanisms. BAFF antagonists
      have been effective in the prevention and treatment of SLE in several different
      murine models. Three classes of BAFF antagonists have been developed for clinical
      use, and initial clinical trials have begun. However, immune modulation in SLE is
      complicated by differences in the immune defects between patients and at
      different disease stages. Further work will be needed both in animal models and
      humans to determine the most appropriate clinical applications for BAFF blockade.

PMID- 18613836
TI  - Understanding the mechanistic basis in rheumatoid arthritis for clinical response
      to anti-CD20 therapy: the B-cell roadblock hypothesis.
AB  - SUMMARY: With the clinical introduction of the anti-CD20 antibody rituximab for
      the treatment of rheumatoid arthritis (RA), B-cell-targeted therapy has become an
      accepted strategy for the treatment of a common chronic inflammatory disease.
      From recently reported synovial biopsy studies, we can begin to develop a
      pathophysiologic model of the sequential synovial cellular and molecular changes
      induced by rituximab infusions. These findings may explain how the rapid and
      early depletion of CD20-bearing B cells may later lead to the more far-reaching
      histopathologic changes that are associated with clinical responsiveness. Anti
      CD20 antibody treatments may therefore affect the representation of not only
      mature B lymphocytes and differentiated immunoglobulin-secreting cells but also
      infiltrating cells such as synovial macrophages and fibroblast-like synoviocytes.
      In light of the known prominence of recirculating memory B cells in RA
      pathogenesis, we propose that clinical efficacy also in part reflects the
      development of an effective blockade of the recirculation of potentially
      pathologic B cells that may prevent reseeding of pathologic synovial ectopic
      lymphoid tissues.

PMID- 18613838
TI  - Inhibition of the lymphotoxin pathway as a therapy for autoimmune disease.
AB  - SUMMARY: The lymphotoxin (LT) system is part of the tumor necrosis factor family
      and is required for lymph node development. It has provided a wonderful tool for
      the dissection of processes critical not only for lymphoid organ development but
      also the maintenance of the adult immune architecture and the formation of
      ectopic organized lymphoid tissues in chronically inflamed sites. A soluble
      lymphotoxin-beta receptor-immunoglobulin (LTbetaR-Ig) fusion protein can block
      this pathway and is currently being tested in the treatment of autoimmune
      disease. This review focuses on the immunological consequences of combined LT and
      LIGHT inhibition with LTbetaR-Ig administration as distinct from the
      developmental biology.

PMID- 18613839
TI  - Modulating tone: the overture of S1P receptor immunotherapeutics.
AB  - SUMMARY: Modulation of complex functions within the immune system has proven to
      be surprisingly sensitive to alterations in the lysophospholipid sphingosine 1
      phosphate (S1P) receptor-ligand rheostat. This has become increasingly evident
      from both chemical and genetic manipulation of the S1P system, with
      pharmacological effects upon lymphoid cells, dendritic cell function, as well as
      vascular interfaces. The integrated immune system, perhaps as a result of its
      relatively recent evolutionary ontogeny, has selected for a number of critical
      control points regulated by five distinct high affinity G-protein-coupled
      receptor subtypes with a shared ligand, with receptors distributed on
      lymphocytes, dendritic cells, and endothelium. All of these cellular components
      of the axis are capable of modulating immune responses in vivo, with the impact
      on the immune response being very different from classical immunosuppressants, by
      virtue of selective spatial and temporal sparing of humoral and myeloid elements
      of host defense. Pharmacological subversion of the S1P rheostat is proving to be
      clinically efficacious in multiple sclerosis, and both the scope and limitations
      of therapeutic modulation of the S1P axis in immunotherapy are becoming clearer
      as understanding of the integrated chemical physiology of the S1P system emerges.

PMID- 18613837
TI  - Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways.
AB  - SUMMARY: Cytokines mediate key communication pathways essential for regulation of
      immune responses. Full activation of antigen-responding lymphocytes requires
      cooperating signals from the tumor necrosis factor (TNF)-related cytokines and
      their specific receptors. LIGHT, a lymphotoxin-beta (LTbeta)-related TNF family
      member, modulates T-cell activation through two receptors, the herpesvirus entry
      mediator (HVEM) and indirectly through the LT-beta receptor. An unexpected
      finding revealed a non-canonical binding site on HVEM for the immunoglobulin
      superfamily member, B and T lymphocyte attenuator (BTLA), and an inhibitory
      signaling protein suppressing T-cell activation. Thus, HVEM can act as a
      molecular switch between proinflammatory and inhibitory signaling. The non
      canonical HVEM-BTLA pathway also acts to counter LTbetaR signaling that promotes
      the proliferation of antigen-presenting dendritic cells (DCs) within lymphoid
      tissue microenvironments. These results indicate LTbeta receptor and HVEM-BTLA
      pathways form an integrated signaling circuit. Targeting these cytokine pathways
      with specific antagonists (antibody or decoy receptor) can alter lymphocyte
      differentiation and activation. Alternately, agonists directed at their cell
      surface receptors can restore homeostasis and potentially reset immune and
      inflammatory processes, which may be useful in treating autoimmune and infectious
      diseases and cancer.

PMID- 18613840
TI  - Integrin-associated proteins as potential therapeutic targets.
AB  - SUMMARY: Integrins are adhesion receptors important for hematopoiesis, leukocyte
      trafficking, and formation of immunological synapses; hence, they may provide
      targets for therapeutic intervention in leukocyte-driven pathologies. Blocking
      integrin-ligand binding is one strategy for inhibiting integrins; however, a
      complete loss of integrin function can lead to mechanism-based toxicities.
      Because integrin alpha and beta subunits interact with a variety of other
      proteins to receive and transmit cellular signals, targeting these integrin
      associated proteins may utilize alternative sites for intervention that lead to
      therapies with fewer side effects. This review summarizes integrin-associated
      proteins in leukocytes and focuses on four of these proteins with perceived
      therapeutic potential. Specific mutations in the alpha4 integrin cytoplasmic tail
      block or enforce binding to paxillin and thus modulate integrin signaling
      required for efficient cell migration. Similarly, the association of RAPL(NORE1B)
      with beta2 integrins may participate in adhesive and migratory events in
      leukocytes. The beta integrin cytoplasmic tail-binding protein talin is critical
      for increasing the affinity of integrins (activation), and blockade of talin
      binding can prevent leukocyte arrest on the endothelium. Finally, the membrane
      protein CD98 mediates beta1 and beta3 integrin signaling and may be involved in
      leukocyte functions. Identification of biologically important interactions of
      integrins and signaling proteins can thus pave the way to new strategies for
      manipulating leukocyte functions.

PMID- 18613841
TI  - The role and therapeutic implications of fibroblast-like synoviocytes in
      inflammation and cartilage erosion in rheumatoid arthritis.
AB  - SUMMARY: Fibroblast-like synoviocytes (FLS) are resident mesenchymal cells of
      synovial joints that have been recognized to play an increasingly important role
      in the pathogenesis of rheumatoid arthritis (RA). Activation of FLS in the
      setting of RA leads to the production of a broad array of cell surface and
      soluble mediators that help to recruit, retain, and activate both cells of the
      immune system and resident joint cells, leading to the promotion of ongoing
      inflammation and tissue destruction. The ability of FLS to stimulate both
      inflammation and tissue damage suggests that this cell type may be a unique
      target for the treatment of inflammatory arthritis. Greater understanding of how
      FLS are activated and how they interact with other cells in the RA synovium may
      provide insights that allow development of novel agents for RA therapy.

PMID- 18613842
TI  - Development of TLR inhibitors for the treatment of autoimmune diseases.
AB  - SUMMARY: The innate immune system is a critical element of protection from
      invading pathogens. The specific receptors that recognize various components of
      the pathogens trigger signals that result in the production of proinflammatory
      cytokines as well as the activation of antigen-presenting cells, which activate
      the adaptive immune system. The discovery of the Toll-like receptors (TLRs) as
      important components of pathogen recognition has brought new understanding of the
      key signaling molecules involves in innate immune activation. Interestingly, it
      appears that most TLRs can recognize self-ligands as well and that mechanisms are
      required to discriminate between self and non-self ligands. One of these
      mechanisms is the expression of all the nucleic acid-specific TLR in endosomal
      compartments and not on the cell surface. Inappropriate activation of TLRs by
      self-components can result in sterile inflammation or autoimmunity. For example,
      TLR7 and TLR9 activation by endogenous RNA and DNA, transported to the endosomes
      in the form of immune complexes or non-covalently associated with cationic
      peptides, could be an important mechanism involved in promoting diseases such as
      systemic lupus erythematosus and psoriasis. In this review, we discuss the
      rationale for self-recognition by TLR7 and TLR9 as an important part of the
      development of lupus and other autoimmune diseases. We describe novel inhibitors
      of these receptors and provide evidence to support their use as novel therapeutic
      agents for autoimmunity.

PMID- 18613843
TI  - B-lymphocyte contributions to human autoimmune disease.
AB  - SUMMARY: Autoimmunity results from abnormal B- and T-cell recognition of self
      antigens, which leads to autoantibody production in many cases. Autoantibodies
      produced by B-cell-derived plasma cells provide diagnostic markers for
      autoimmunity but also contribute significantly to disease pathogenesis. As
      discussed in this review, the therapeutic benefit of depleting B cells in mice
      and humans has refocused attention on B cells and their role in autoimmunity
      beyond autoantibody production. B cells specifically serve as cellular adjuvants
      for CD4(+) T-cell activation, while regulatory B cells, including those that
      produce interleukin-10 (B10 cells), function as negative regulators of
      inflammatory immune responses. The emerging picture is that B cells,
      autoantibodies, and T cells are all important components of abnormal immune
      responses that lead to tissue pathology unique to each autoimmune disease, with
      their relative contributions changing during disease progression. Autoimmune
      diseases where B-cell functions are closely correlated with disease activity
      include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, type 1
      diabetes, and multiple sclerosis. Understanding the overlapping roles of B cells
      as mediators of autoimmune disease will facilitate the development of more
      precisely directed therapies and combination therapies with broader clinical
      efficacy than current depletion strategies that remove all B cells.

PMID- 18613844
TI  - The spectrum of complement alternative pathway-mediated diseases.
AB  - SUMMARY: The complement system has once again come into prominence in the
      therapeutic development arena. The recent approval of an inhibitory monoclonal
      antibody, eculizumab, which is directed against complement component C5 for the
      disease paroxysmal nocturnal hemoglobinuria has provided the initial validation
      of this system as a therapeutic target. Preclinical studies using animal models
      and human-derived samples demonstrate that inhibition of complement ameliorates
      many inflammatory and autoimmune disease manifestations. Major efforts continue
      to define the most optimal means to block complement activation in a cost
      effective manner. Because the system is initiated through three pathways and
      generates at least six immunoregulatory and pro-inflammatory mediators, there is
      substantial complexity to this problem. One pathway, designated the alternative
      pathway, has recently been shown to play a particularly important role in
      preclinical disease models. Further evidence of the importance of the alternative
      pathway has been provided by studies of human diseases, where mutations or
      dysfunctional polymorphisms that promote activation of this pathway are highly
      associated with the diseases atypical hemolytic uremic syndrome, dense deposit
      disease, and age-related macular degeneration. This article reviews evidence in
      support of the essential role of the alternative pathway in the generation of
      tissue injury and the rationale for development of therapies that modulate its
      activity.

PMID- 18613845
TI  - Manipulating both the inhibitory and stimulatory immune system towards the
      success of therapeutic vaccination against chronic viral infections.
AB  - SUMMARY: One potentially promising strategy to control chronic infections such as
      human immunodeficiency virus, hepatitis B virus, and hepatitis C virus is
      therapeutic vaccination, which aims to reduce persisting virus by stimulating a
      patient's own antiviral immune responses. However, this approach has fallen short
      of expectations, because antiviral T cells generated during chronic infections
      often become functionally exhausted and thus do not respond properly to
      therapeutic vaccination. Therefore, it is necessary to develop a therapeutic
      vaccine strategy to more effectively boost endogenous T-cell responses to control
      persistent viral infections. Studies to elucidate the cause of impaired T-cell
      function have pointed to sustained inhibitory receptor signaling through T-cell
      expression of programmed death 1 (PD-1). Recently, another inhibitory molecule,
      cytotoxic T lymphocyte antigen 4 (CTLA-4), and also an immunosuppressive
      cytokine, interleukin 10 (IL-10), have been reported to be potential factors of
      establishing immune suppression and viral persistence. Blocking these negative
      signaling pathways could restore the host immune system, enabling it to respond
      to further stimulation. Indeed, combining therapeutic vaccination along with the
      blockade of inhibitory signals could synergistically enhance functional CD8(+) T
      cell responses and improve viral control in chronically infected mice, providing
      a promising strategy for the treatment of chronic viral infections. Furthermore,
      not only the ablation of negative signals but also the addition of stimulatory
      signals, such as interleukin 2 (IL-2), might prove to be a potentially promising
      strategy to augment the efficacy of therapeutic vaccination against chronic viral
      infections.

PMID- 18613847
TI  - Reprogramming the immune system: co-receptor blockade as a paradigm for
      harnessing tolerance mechanisms.
AB  - SUMMARY: The challenge of harnessing tolerance as a therapeutic modality has been
      greatly influenced by dogmas dictating how self-tolerance comes about. Deletional
      strategies popularized from the classical work of Medawar and Owen have always
      demanded stringent attention to eliminating all antigen-reactive cells. This was
      always considered a tough call for the treatment of autoimmune disease, where the
      number of antigens and their identity were hard to predict. The finding, some 15
      years ago, that therapeutic tolerance could be elicited with non-lytic CD4
      monoclonal antibodies using regulatory T cells as major operatives has opened up
      a new dimension in exploiting tolerance mechanisms for drug minimization in
      transplantation and for providing short-term treatments for long-term benefit in
      allergy, autoimmunity, transplantation, and other immunopathological conditions.
      Resolution of the mechanisms underlying tolerance induced by CD4 co-receptor
      blockade have provided a general paradigm for how regulatory T cells might be
      directed to get the upper hand in preventing disease. They have also identified
      an unexpected role for tissues to contribute to their own protection.

PMID- 18613848
TI  - Human regulatory T cells: role in autoimmune disease and therapeutic
      opportunities.
AB  - SUMMARY: The importance of regulatory T lymphocytes (Tregs) in the control of
      autoimmunity is now well established in a variety of experimental animal models.
      In addition, there are numerous studies suggesting that Treg deficits may be an
      underlying cause of human autoimmune diseases. The emergence of Tregs as an
      essential component of immune homeostasis provides a potential therapeutic
      opportunity for active immune regulation and long-term tolerance induction. In
      this article, we summarize the core basic science and animal model studies of
      Tregs, review the status of multiple biologic and small molecule chemical
      compounds to promote Treg development in vivo, and discuss recent advances for
      the identification and expansion of polyclonal and antigen-specific Tregs for
      adoptive immunotherapy. In summary, the review provides an in-depth analysis and
      highlights the challenges and opportunities for immune intervention with Treg
      based therapeutics.

PMID- 18613849
TI  - CD4+ T-regulatory cells: toward therapy for human diseases.
AB  - SUMMARY: T-regulatory cells (Tregs) have a fundamental role in the establishment
      and maintenance of peripheral tolerance. There is now compelling evidence that
      deficits in the numbers and/or function of different types of Tregs can lead to
      autoimmunity, allergy, and graft rejection, whereas an over-abundance of Tregs
      can inhibit anti-tumor and anti-pathogen immunity. Experimental models in mice
      have demonstrated that manipulating the numbers and/or function of Tregs can
      decrease pathology in a wide range of contexts, including transplantation,
      autoimmunity, and cancer, and it is widely assumed that similar approaches will
      be possible in humans. Research into how Tregs can be manipulated therapeutically
      in humans is most advanced for two main types of CD4(+) Tregs: forkhead box
      protein 3 (FOXP3)(+) Tregs and interleukin-10-producing type 1 Tregs (Tr1 cells).
      The aim of this review is to highlight current information on the characteristics
      of human FOXP3(+) Tregs and Tr1 cells that make them an attractive therapeutic
      target. We discuss the progress and limitations that must be overcome to develop
      methods to enhance Tregs in vivo, expand or induce them in vitro for adoptive
      transfer, and/or inhibit their function in vivo. Although many technical and
      theoretical challenges remain, the next decade will see the first clinical trials
      testing whether Treg-based therapies are effective in humans.

PMID- 18613850
TI  - Retinoic acid syndrome: a review.
AB  - The retinoic acid syndrome (RAS) is an unpredictable but frequent complication
      which may develop after administration of all-trans retinoic acid (ATRA) most
      commonly in patients with acute promyelocytic leukaemia (APL). In this review, we
      describe the incidence, predictive factors, clinical course, outcome and
      treatment of RAS in patients with APL treated with ATRA. The incidence of RAS in
      patients receiving ATRA is about 14-16%, with an associated mortality of about
      2%. Initial high white blood cell (WBC) count, rapidly increasing WBC count
      and/or the presence of the CD 13 expression on leukaemic cells may help in
      identifying patients likely to develop RAS. Concurrent chemotherapy will probably
      decrease the risk of developing RAS but often exacerbates bleeding, leading to
      leucocytosis, thrombocytopenia, disseminated intravascular coagulation and
      fibrinolysis. Prophylactic steroids are not recommended but prompt administration
      of steroids at the first sign of unexplained dyspnea, fever, weight gain or
      pulmonary infiltrate, is critical. Liposomal ATRA is being investigated to induce
      haematological cure in APL without chemotherapy and to reduce the incidence of
      RAS but further validation of its usefulness is necessary.

PMID- 18613846
TI  - Manipulating the immune system for anti-tumor responses and transplant tolerance
      via mixed hematopoietic chimerism.
AB  - SUMMARY: Stem cells (SCs) with varying potentiality have the capacity to repair
      injured tissues. While promising animal data have been obtained, allogeneic SCs
      and their progeny are subject to immune-mediated rejection. Here, we review the
      potential of hematopoietic stem cells (HSCs) to promote immune tolerance to
      allogeneic and xenogeneic organs and tissues, to reverse autoimmunity, and to be
      used optimally to cure hematologic malignancies. We also review the mechanisms by
      which hematopoietic cell transplantation (HCT) can promote anti-tumor responses
      and establish donor-specific transplantation tolerance. We discuss the barriers
      to clinical translation of animal studies and describe some recent studies
      indicating how they can be overcome. The recent achievements of durable mixed
      chimerism across human leukocyte antigen barriers without graft-versus-host
      disease and of organ allograft tolerance through combined kidney and bone marrow
      transplantation suggest that the potential of this approach for use in the
      treatment of many human diseases may ultimately be realized.

PMID- 18613851
TI  - Factors affecting the uptake of new medicines in secondary care - a literature
      review.
AB  - BACKGROUND AND OBJECTIVE: The rate of uptake of new medicines in the UK is slower
      than in many other OECD countries. The majority of new medicines are introduced
      initially in secondary care and prescribed by specialists. However, the reasons
      for relatively low precribing levels are poorly understood. This review explores
      the determinants of uptake of new medicines in secondary care. METHODS: Nine
      electronic databases were searched covering the period 1992-2006. Once the
      searches had been run, records were downloaded and those which evaluated uptake
      of new medicines in secondary care were identified. UK studies were of primary
      interest, although research conducted in other countries was also reviewed if
      relevant. With the exception of 'think pieces', eligibility was not limited by
      study design. Studies published in languages other than English were excluded
      from the review. Determinants of uptake in secondary care were classified using
      Bonair and Persson's typology for determinants of the diffusion of innovation.
      RESULTS: Almost 1400 records were screened for eligibility, and 29 studies were
      included in the review. Prescribing of new medicines in secondary care was found
      to be subject to a number of interacting influences. The support structures which
      exist within secondary care facilitate access to other colleagues and shape
      prescribing practices. Clinical trial investigators and physicians who sit on
      decision-making bodies such as Drug and Therapeutic Committees (DTCs) appear to
      have a special influence due to their proximity to their research and
      understanding of evidence base. Pharmaceutical representatives may also influence
      prescribing decisions through funding of meetings and academic detailing, but
      clinicians are wary of potential bias. Little evidence on the influence of
      patients upon prescribing decisions was identified. The impact of clinical
      guidelines has been variable. Some guidelines have significantly increased the
      uptake of new medicines, but others have had little discernible impact despite
      extensive dissemination. However given the increasing influence of the National
      Institute for Health and Clinical Excellence, guidelines may become more
      important. The impact of financial prescribing incentives on secondary care
      prescribing is unclear. Although cost and budget may influence hospital
      prescribing of new drugs, they are of secondary importance to the safety and
      effectiveness profile of the medicine. If a drug has a novel mechanism of action,
      or belongs to a class with few alternatives, clinicians are more likely to
      consider it favourably as a prescribing option. CONCLUSIONS: Although price does
      not appear to be a primary factor behind prescribing decision-making, in
      secondary care there has long been a historical need for formal purchasing
      decisions through the DTC, which differentiates it from primary care. This, in
      addition to increasing pressures for cost-effectiveness within the NHS means that
      cost will appear more frequently on clinician consciousness. As a result,
      guidelines are more likely to be implemented using the strong professional
      networks in existence within secondary care, and although the influence of
      patients has not been addressed by the literature, they are likely to have an
      increasing input into the prescribing decision, given the importance of patient
      involvement in current UK policy.

PMID- 18613852
TI  - Aldosterone receptor antagonism and heart failure: insights from an outpatient
      clinic.
AB  - OBJECTIVE: In randomized clinical trials, aldosterone antagonists have been shown
      to reduce mortality and morbidity in heart failure (HF). The aim of the present
      study was to examine the risk-benefit profile of aldosterone antagonists in
      routine clinical practice. METHODS: A retrospective analysis, extending over a 1
      year period, of the clinical, instrumental and laboratory data of 264 HF
      outpatients was performed. All patients were on a beta-blocker and an ACE
      inhibitor (or angiotensin-II receptor-blocker) and 151 were taking an aldosterone
      antagonist. RESULTS: At baseline, subjects treated with aldosterone antagonists
      had a higher NYHA class, a larger left-ventricular end-diastolic volume, a worse
      ejection fraction and a higher systolic pulmonary arterial pressure (sPAP).
      During follow-up, a greater reduction in sPAP and a tendency towards improved
      systolic and diastolic function were observed in subjects treated with
      aldosterone antagonists. Moreover, clinical and laboratory parameters did not
      deteriorate in patients taking aldosterone antagonists. Mortality rates were
      similar in the two groups (8.6% vs. 8.8%, P = NS). CONCLUSIONS: The use of
      aldosterone antagonists in HF is associated with an improvement in cardiac
      function and is well tolerated. In the present study, patients administered these
      agents had a comparable clinical outcome to that of the control group, despite
      important differences in baseline risk.

PMID- 18613853
TI  - Analysis using fluorescence polarization immunoassay for unbound teicoplanin
      concentration in serum.
AB  - OBJECTIVES: The aim of this study was to develop a simpler and more rapid
      analytical method for unbound teicoplanin in serum. METHODS: A new analytical
      method was developed by modifying an existing fluorescence polarization
      immunoassay (FPIA) method. The validation of the developed FPIA method was
      compared in the quantification of unbound teicoplanin with that of the high
      performance liquid chromatography (HPLC) method reported previously. The
      developed FPIA method was employed for the measurement of 36 clinical samples
      collected from patients with methicillin-resistant Staphylococcus aureus (MRSA)
      infection. RESULTS: The limits of detection and quantification were 0.5 and 0.8
      mug/mL, respectively. The recovery rate was 97.5-106.6%. The developed FPIA
      method showed better accuracy than the HPLC method. The within-run and interday
      reproducibility of the assay was good, with relative standard deviation values of
      4.76-18.75% (within-run) and 5.68-13.95% (interday). Precision and accuracy of
      this method were within the acceptable limits defined in the US FDA Guidance for
      bioanalytical method validation. The correlation between the developed FPIA
      method and the HPLC method was good (r(2) = 0.87). A positive bias with the FPIA
      method was observed from the result of the Bland-Altman difference plot.
      CONCLUSION: We firmly believe that the present method is useful for the
      adjustment of teicoplanin dosages for patients under various conditions.

PMID- 18613854
TI  - Economic evaluation in Sweden of epoetin beta with intravenous iron
      supplementation in anaemic patients with lymphoproliferative malignancies not
      receiving chemotherapy.
AB  - BACKGROUND AND OBJECTIVE: Functional iron deficiency is one reason for lack of
      response to erythropoietin treatment. Concomitant intravenous (IV) iron
      supplementation has the potential to improve response to erythropoietin, allowing
      a decrease in erythropoietin dose requirements. In a recent study of anaemic,
      iron-replete patients with lymphoproliferative malignancies (Leukemia, 21, 2007,
      627), the haemoglobin (Hb) increase and response rate were significantly greater
      in patients receiving epoetin beta with concomitant IV iron compared with
      patients receiving epoetin beta without IV iron (P < 0.05). The present analysis
      aimed to investigate whether a combination of epoetin beta and IV iron is cost
      effective compared with epoetin beta without IV iron. METHODS: This analysis was
      performed from a Swedish societal perspective as a within-trial evaluation of
      overall costs (based on differences in drug costs and resource use between
      groups) and effect (differences in Hb increases) during 16 weeks' treatment with
      epoetin beta with or without concomitant IV iron. RESULTS AND DISCUSSION: There
      was an improved response to epoetin beta with IV iron therapy and an almost 2
      fold greater increase in Hb levels. Overall mean cost per patient in the epoetin
      beta with IV iron group was euro5558 and in the epoetin beta without IV iron
      group was euro6228. Thus, treatment with epoetin beta with IV iron resulted in
      overall cost savings of about 11% compared with epoetin beta without iron, mainly
      due to reduced erythropoietin dosages. CONCLUSION: Epoetin beta with concomitant
      IV iron in anaemic patients with lymphoproliferative malignancies not receiving
      chemotherapy resulted in better outcomes at lower cost compared with epoetin beta
      without iron. This suggests that epoetin beta with IV iron is a dominant therapy
      from a Swedish perspective.

PMID- 18613855
TI  - Quality of amoxicillin formulations in some Arab countries.
AB  - BACKGROUND AND OBJECTIVE: The problem of counterfeit and substandard drugs is
      recurrent in developing countries where antibiotics account for the majority of
      such products. The aim of this study was to investigate the quality of locally
      produced and imported amoxicillin products on the Lebanese, Jordanian, Egyptian
      and Saudi markets. METHODS: One hundred and eleven samples of amoxicillin
      capsules and suspensions purchased from retail pharmacies were analysed for their
      drug content by a validated chromatographic method in order to verify if they
      complied with pharmacopeial requirements. Suspensions were analysed for their
      drug content immediately after reconstitution as well as 7 or 14 days later
      according to the expiry date. RESULTS AND DISCUSSIONS: Fifty-six per cent of
      amoxicillin capsules did not meet the United State Pharmacopeia (USP)
      requirements and most had amounts bordering the lower limit. Individual average
      values as low as 59% of the label claim were detected. Eight per cent of the
      samples of suspensions gave measurements outside pharmacopeial limits.
      Furthermore, after 7 or 14 days, 38% of the samples were outside the
      pharmacopeial limits. All the European brands met the pharmacopeial limits except
      for one. CONCLUSION: Our results reveal the high incidence of substandard drugs
      on some Arab market where several factors might jeopardize the quality status of
      medicines: lack of effective quality assurance system during manufacture in both
      Arab and export countries, and uncontrolled storage conditions, especially
      unsuitable pharmacy premises. Use of substandard antibiotic preparations
      increases the risk of therapeutic failure and the emergence of drug-resistant
      microorganisms.

PMID- 18613856
TI  - Factors influencing the use of potentially inappropriate medication in older
      patients in Slovakia.
AB  - BACKGROUND: Although increasing attention has been given to the evaluation of use
      of potentially inappropriate medication in the older European Union (EU) member
      countries, information on this topic from Central and Eastern Europe is scarce.
      OBJECTIVES: The aims of the present study were: to identify risk factors
      enhancing the probability of use of potentially inappropriate medication in
      hospitalized older patients under the conditions of the Slovak healthcare system
      and to compare our results with previously published European studies. METHODS:
      The evaluation was performed in 600 patients aged > or =65 years, hospitalized in
      a general hospital between 1 December 2003 and 31 March 2005. To identify the use
      of potentially inappropriate medication, the Beers 2003 criteria were applied.
      Particular socio-demographic and clinical characteristics, as well as comorbid
      medical conditions were evaluated among possible factors enhancing the
      probability of use of potentially inappropriate medication. RESULTS: At least one
      potentially inappropriate medication was prescribed to 126 (21%) of 600 patients.
      Multivariate analysis identified polypharmacy [odds ratio (OR) 2.38; 95%
      confidence interval (CI): 1.50-3.79], depression (OR 2.03; 95% CI: 1.08-3.82),
      immobilization (OR 1.87; 95% CI: 1.16-3.00) and heart failure (OR 1.73; 95% CI:
      1.13-2.64) as factors associated with an increased risk of use of inappropriate
      medication. In contrast, patients aged > or =75 years had a lower risk of being
      prescribed potentially inappropriate medication (OR 0.58; 95% CI: 0.39-0.88).
      CONCLUSIONS: Polypharmacy, immobilization, heart failure and depression were
      documented as predictors of use of potentially inappropriate medication. In
      depressive patients, drugs other than antidepressants contributed to the
      extensive use of potentially inappropriate medication. The observed prevalence of
      use of potentially inappropriate medication in older hospitalized Slovak patients
      was lower than the prevalence previously documented in Poland and the Czech
      Republic, but higher than in Croatia and Turkey. The identified risk factors were
      consistent with previous findings from other parts of Europe.

PMID- 18613857
TI  - Prevalence of possible drug-drug interactions between antiretroviral agents in
      different age groups in a section of the private health care sector setting in
      South Africa.
AB  - BACKGROUND: The chronic nature of human immunodeficiency virus (HIV) infection
      requires lifelong highly active antiretroviral (ARV) therapy (HAART) to
      continuously suppress HIV-1 viral replication, thus reducing morbidity and
      mortality. HAART is restricted by complex dosing, drug-drug interactions (DDIs)
      and toxicities. OBJECTIVE: To determine the prevalence of possible DDIs between
      ARV drugs in different age groups in a section of the private primary health care
      sector in South Africa. METHODS: A quantitative, retrospective drug utilization
      review was performed on 47 085 ARV prescriptions claimed through a national
      medicine claims database during 2006. Possible DDIs identified were classified
      according to a clinical significance rating as described by Tatro [Drug
      Interaction Facts 2005. St Louis, MO: Facts and Comparisons (2005)]. RESULTS: The
      total number of patients who received prescriptions that were claimed through the
      medicine claims database was 275 424, of whom 25.11% were males, 28.28% were
      females and the gender of 46.61% patients was unknown. Of the total number of
      patients, 3.27% were HIV patients of which an average of 5.23 +/- 3.86 ARV
      prescriptions (n = 47 085) per patient were claimed for representing 4.73% of the
      total number of prescriptions claimed during the study period (N = 993 804). HIV
      patients received an average of 2.36 +/- 0.61 ARVs per prescription. Only 4.95%
      of the prescriptions had one ARV medicine item, 56.04% two, 37.10% three, 1.75%
      four and <1% had more than four. Of 960 DDIs identified, 1.88% were for patients
      < or =6 years, 4.27% for patients >6 years and < or =12 years, 0.63% for patients
      >12 and < or =19 years, 32.40% for patients <19 years and < or =40 years, 60.21%
      for patients <40 years and < or =60 years and 0.63% for patients >60 years with
      patients <40 years and < or =60 years having the highest number of DDIs and
      patients older than 60 years the lowest. The majority of DDIs between the ARVs
      presented in significance levels 2 and 4. The most important interactions were
      between: indinavir (IDV) and ritonavir (n = 199); efavirenz (EFV) and
      lopinavir/ritonavir (n = 65) and EFV and IDV (n = 60) all interacting at level 2.
      CONCLUSION: The importance of using drug utilization study as an identification
      tool to provide insight into the prescribing and utilization patterns of ARV
      drugs, to provide optimal therapy for patients infected with HIV is emphasized.

PMID- 18613858
TI  - Comparison of follitropin-beta administered by a pen device with conventional
      syringe in an ART programme - a retrospective study.
AB  - OBJECTIVES: This study compares the efficacy and patient tolerance of follitropin
      beta (recagon) administered using a pen device with conventional syringe in
      infertile couples undergoing in vitro fertilization/intracytoplasmic sperm
      injection treatment. METHODS: Data for 481 patients were retrieved
      retrospectively for the analysis. Conventional syringe group constituted 204
      patients with 217 cycles and 265 patients with 294 cycles in the pen-device
      group. Down-regulation was achieved with GnRH agonist. RESULTS: Comparison of
      follitropin-beta administered with pen and syringe showed the following data,
      respectively. A total dose of 1909.38/2100.65 IU (P < 0.001), duration of
      stimulation, 9.70/10.47 days (P < 0.05), oestradiol levels on the day of human
      chorionic gonadotropin, 1488.34/1067.63 pg/ml, number of follicles reaching >16
      mm size, 9.75/7.34 (P < 0.05), number of oocytes retrieved, 13.84/9.55 (P <
      0.001) and number of embryos available for freezing, 4.56/1.30 (P < 0.05), the
      above data were observed in pen/conventional syringe groups, respectively. The
      live birth rates per cycle were 28.85% and 30.95% in the conventional syringe/pen
      device groups, respectively. Patient tolerance with respect to pain at injection
      site was better with the pen device (P < 0.025). CONCLUSION: The data show that
      follitropin-beta administered with pen device is well tolerated and more
      efficacious with respect to ovarian stimulation outcome compared with the
      conventional syringe.

PMID- 18613859
TI  - Serum cystatin C level for better assessment of glomerular filtration rate in
      cystic fibrosis patients treated by amikacin.
AB  - BACKGROUND AND OBJECTIVE: Monitoring of renal function in cystic fibrosis (CF)
      patients is essential. The dosage regimen of amikacin is regularly modified
      according to the patient's glomerular filtration rate (GFR). The aim of the study
      was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along
      with other markers of renal tubular and glomerular function, and damage [N-acetyl
      beta-d glucosaminidase (NAG), creatinine level and creatinine clearance].
      METHODS: We compared the GFR, estimated from the serum concentrations of
      creatinine (Cockcroft-Gault formula) and CyC (Grubb's formula). Seventy-one
      patients (mean age 12 years; range 4-28 years) with CF were treated by
      intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was
      investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U
      creatinine). Concentrations of all markers were measured before starting amikacin
      therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis,
      turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry
      were used for determination of serum amikacin, serum CyC, creatinine and urine
      NAG activity. Receiver operating characteristic (ROC) analysis was performed to
      assess the influence of GFR estimated from serum creatinine and serum CyC for the
      prediction of amikacin clearance during aminoglycoside therapy. RESULTS:
      Significant differences in the rate of U-NAG/U-creatinine were noted before and
      after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine
      clearance at the end of amikacin therapy (12th day) did not show any significant
      differences in comparison with the levels measured before the start of therapy
      (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant
      elevation (P < 0.001), and CyC clearance showed a significant decrease (P <
      0.001) in comparison with the levels measured at day 0. The ratio of amikacin
      clearance/creatinine clearance decreased with therapy whereas the amikacin
      clearance/CyC and amikacin clearance/CyC clearance increased. CONCLUSION: We
      showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring
      tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine
      clearance are modest predictors of GFR in CF patients. CyC appears to be a better
      marker of GFR than serum creatinine concentration or creatinine clearance in our
      study. Serum CyC levels and CyC clearance showed greater ability to predict
      amikacin clearance during therapy than creatinine clearance.

PMID- 18613860
TI  - Rapid and sensitive quantitation of morphine using HPLC with electrochemical
      detection.
AB  - BACKGROUND: Morphine is one of the most widely used opioid analgesics for
      controlling pain in cancer and post-operative patients. OBJECTIVE: This study
      aimed at finding a sensitive method for measuring morphine. METHOD: A one-step
      solid phase extraction was developed for extracting morphine from various
      samples, and morphine concentration was measured using a high-performance liquid
      chromatographic system with electrochemical detection. The sensitivity of the
      assay was 1.53 ng/mL with a recovery of 93.4% +/- 0.01. The mean intra-assay and
      inter-assay test for three concentrations was 10.54 and 7.47, respectively. The
      assay showed no cross-reaction with a wide range of compounds. CONCLUSION: This
      method for morphine in small biological samples is easy, sensitive and
      reproducible with low cross-reactivity.

PMID- 18613861
TI  - Pharmacokinetics and tolerability of modafinil tablets in Chinese subjects.
AB  - OBJECTIVE: To investigate the pharmacokinetics and tolerability of modafinil in
      Chinese subjects. METHODS: Twelve healthy volunteers were given an escalating
      single dose of modafinil (100, 200 and 400 mg) in a three-period study (study 1).
      Another 12 volunteers received 100 mg twice daily for 7 days in multiple-dose
      study (study 2). Blood samples were taken from 0 to 60 h for study 1. And samples
      for study 2 were collected before administration on three consecutive morning and
      then from 0 to 60 h after the last dose. Pharmacokinetic parameters were
      calculated and compared with results from published data. RESULTS: In study 1,
      C(max) and area under the concentration-time curve of modafinil and modafinil
      acid were increased proportionally with dose levels; t(1/2) was independent on
      the dose levels. In study 2, the steady state was reached on day 4, and mean
      trough plasma concentration of modafinil was 1.36 +/- 0.34 mug/mL. Apparent
      plasma clearance and apparent volume of distribution were lower in 100 mg twice
      daily group than those in 100 mg single group. The adverse events were mild and
      moderate in study 1 and 2. CONCLUSIONS: In this pharmacokinetic study, modafinil
      was safe and well tolerated by young healthy Chinese subjects. The major
      pharmacokinetic parameters of modafinil in Chinese subjects are similar to those
      reported in Caucasians although the half-life seems to be longer in the former
      than in the latter. This apparent difference requires investigation.

PMID- 18613862
TI  - Smoking behaviour modulates pharmacokinetics of orally administered clopidogrel.
AB  - BACKGROUND AND OBJECTIVES: Clopidogrel is an important antiplatelet drug that is
      effective in preventing thrombotic events, especially for patients undergoing
      percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has
      been limited by documented inter-individual heterogeneity in platelet inhibition,
      which may be attributable to known clopidogrel pharmacokinetic variability. The
      objective of this study was to assess the influence of smoking cigarettes and
      abnormal body weight on the pharmacokinetics of clopidogrel. METHODS: Seventy-six
      healthy adult male volunteers were selected randomly. Each subject received a
      single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel
      carboxylate plasma levels were measured and non-compartmental analysis was used
      to determine peak plasma concentration (C(max)), time to peak plasma
      concentration (T(max)), elimination half-life (t(1/2e)), and area under the curve
      (AUC(0-->infinity)). RESULTS: One-third of volunteers were smokers (n = 27) and
      one-half had abnormal body weight (n = 39). Smokers had lower AUC(0-->infinity)
      (smokers: 6.24 +/- 2.32 microg/h/mL vs. non-smokers: 8.93 +/- 3.80 microg/h/mL, P
      < 0.001) and shorter half-life (smokers: 5.46 +/- 2.99 vs. non-smokers: 8.43 +/-
      4.26, P = 0.001). Smoking behaviour had no influence on C(max) (P = 0.3) and
      T(max) (P = 0.7). There was no statistically significant difference in C(max),
      AUC(0-->infinity), T(max) and t(1/2e) between volunteers with abnormal body
      weight and normal body weight. However the difference in body weight of the two
      groups was relatively narrow (mean +/- SE; 26.93 +/- 0.16 vs. 23.11 +/- 0.27). In
      general, the pharmacokinetic parameters were characterized by considerable inter
      individual differences (C(max) = 3.09 +/- 0.99 microg/mL, CV = 32%), (T(max)
      =0.76 +/- 0.24 h, CV = 31.6%), (AUC(0-->infinity) = 7.98 +/- 3.58 microg/h/mL, CV
      = 44.8%), and (t(1/2e) = 7.38 +/- 4.10 h, CV = 55.6%). CONCLUSION: Smoking is a
      significant factor affecting the pharmacokinetics of clopidogrel, following
      administration of a single 75 mg dose in healthy young volunteers. The study
      supports smoking-cessation recommendations. Further studies are required to
      evaluate the influence of smoking and body weight on the pharmacokinetics of the
      active metabolite of clopidogrel and on the clinical effects of any differences
      observed.

PMID- 18613863
TI  - Colchicine intoxication and infection risk: a case report.
AB  - Colchicine is widely used, primarily for the treatment of gouty arthritis and
      familial Mediterranean fever. Colchicine intoxication is a rare but potentially
      life-threatening event. Herein, we reported a 26-year-old woman who presented to
      the emergency department after ingesting 27.5 mg of colchicine in a suicide
      attempt. She exhibited signs typical of colchicine-poisoning and developed
      infectious complications but with subsequent complete recovery. This paper
      discusses the role of colchicine poisoning in increasing susceptibility to
      infections. This aspect is usually under-appreciated in the clinical picture of
      colchicine overdose.

PMID- 18613864
TI  - Tamoxifen-induced QT interval prolongation.
AB  - We report on a case of tamoxifen-induced QT interval prolongation in a 56-year
      old-female patient with hormone-dependent carcinoma of the right breast, stage
      T2N0M0, grade 3 and HER-2 negative. Partial mastectomy with axillary lymph node
      excision was performed in July 2007 with adjuvant hormonal and radiation therapy.
      This case highlights the risk of tamoxifen causing depression of electrical
      impulse in the sino-atrial node, leading to symptomatic sinus bradycardia with
      prolonged QT interval. It indicates the necessity of regular monitoring of
      patients undergoing tamoxifen treatment. ECG should be performed not only before
      and after, but also during treatment. with an average duration of treatment of 5
      years, we would advise an annual ECG for asymptomatic patients. In the presence
      of symptomatic sinus bradycardia, constant monitoring is necessary. We also
      highlight potential drug interactions, between tamoxifen and acitretin and the
      need to be aware of drugs which may induce QT interval prolongation.

PMID- 18613865
TI  - Valproate: do formulations matter?

PMID- 18613867
TI  - Ancient adaptations of human skin: why do we retain sebaceous and apocrine
      glands?

PMID- 18613868
TI  - Clinicopathologic challenge. Sclerodermoid graft-versus-host disease (GVHD) with
      lichensclerosus-like lesions.

PMID- 18613869
TI  - Kindler syndrome: a study of five Egyptian cases with evaluation of severity.
AB  - BACKGROUND: Kindler syndrome (KS) is a rare genodermatosis characterized by four
      major features (acral blisters, photosensitivity, poikiloderma, and cutaneous
      atrophy) and many associated findings. The diagnosis of KS includes clinical
      features, ultrastructural findings, and, recently, immunostaining and genetic
      studies. Varying degrees of severity of the syndrome have been described.
      METHODS: Five patients with clinical features consistent with KS were included in
      this study. All patients were subjected to histopathologic and ultrastructural
      studies. RESULTS: Cases 1 and 2 presented with severe major features, severe
      mucosal involvement, and many other associated findings. Case 3 presented with
      severe major features, but mild and limited mucosal involvement and other
      associated findings. Cases 4 and 5 showed mild major features and few other
      findings. Histopathology revealed nonspecific poikiloderma. Marked thickening of
      the lamina densa and splitting of the lamina lucida were the main ultrastructural
      findings. CONCLUSION: KS may be classified into mild, moderate, and severe
      according to the severity of the major features and mucosal involvement. Because
      histopathologic and ultrastructural findings are not pathognomonic, clinical
      features remain the mainstay for the diagnosis of KS, and the need for
      immunostaining with kindlin antibody and genetic studies may be restricted to
      early cases with incomplete features.

PMID- 18613870
TI  - Lichenoid inflammation in vitiligo--a clinical and histopathologic review of 210
      cases.
AB  - BACKGROUND: '"Inflammatory vitiligo" cases with clear lichenoid infiltrates have
      been reported. However, the inflammatory nature of common vitiligo has not gained
      wide acceptance because of its benign appearance and scanty cellular infiltrates.
      We have observed in our patients a few lesions with mild erythema, scaling and
      marginal hyperpigmentation which were suspected to be inflammatory. This study
      was conducted to assess the histological features and prevalence of such
      marginally active lesions, in comparison with common vitiligo. METHODS: Two
      hundred and ten consecutive new cases of vitiligo seeking treatment for the first
      time were included in this study. Clinical lesions were carefully examined and
      biopsies were taken in all cases. Biopsies were also taken from pigmented skin 3
      cm away from the vitiligo lesion in 20 cases and normal pigmented skin over the
      contralateral side in 20. RESULTS: Marginally active lesions with erythema,
      scaling and hyperpigmentation were identified in 27 patients (13%). Lymphocytic
      infiltration of dermo-epidermal interface was observed in 89% of these cases
      which was clearly lichenoid in 59%. Similar lichenoid infiltrates were also seen
      in 50% of pigmented skin samples 3 cm away from the lesion and 23% of common
      macular vitiligo lesions. CONCLUSIONS: Vitiligo is an inflammatory disease that
      with development involves a lichenoid tissue reaction.

PMID- 18613871
TI  - Profile of vitiligo in the south of Tunisia.
AB  - BACKGROUND: Vitiligo is a depigmentation disorder characterized by the loss of
      melanocytes from cutaneous cells. Its pathogenesis has not yet been clarified.
      OBJECTIVE: To study the epidemiologic profile of vitiligo in Tunisia and analyze
      its characteristics. METHODS: The clinical presentation of vitiligo was examined
      in 60 patients [27 males (45%) and 33 females (55%)] attending the Medenine
      Hospital Center, a large hospital in the south of Tunisia. RESULTS: The lower
      limbs were the initial site of onset of vitiligo in the majority of patients
      (29.8%), followed by the upper limbs, head and neck, trunk, and mucosae. The most
      common clinical pattern observed was vitiligo vulgaris, followed by focal,
      acrofacial, mucosal, segmental, and universal types. Leukotrichia was observed in
      23%, koebnerization in 18.5%, and a positive family history in 18%. CONCLUSION:
      This study indicates that vitiligo vulgaris is the most common clinical type
      observed in the south of Tunisia. There were associated endocrine disorders in
      some patients, including diabetes, hypothyroidism, and alopecia.

PMID- 18613872
TI  - Primary cutaneous B-cell lymphoma: report of eight cases and review of the
      literature.

PMID- 18613873
TI  - Comparison of the radiometric BACTEC 460 TB culture system and Lowenstein-Jensen
      medium for the isolation of mycobacteria in cutaneous tuberculosis and their drug
      susceptibility pattern.
AB  - BACKGROUND: Mycobacterial isolation from cutaneous tuberculosis on Lowenstein
      Jensen (L-J) medium has been reported to be low. The radiometric BACTEC 460 TB
      culture system (BACTEC system) has shown better isolation rates in pulmonary
      tuberculosis. There has been a progressive increase in the prevalence of
      multidrug resistance in pulmonary tuberculosis, but similar studies are lacking
      for cutaneous tuberculosis. Therefore, this study was undertaken to compare
      mycobacterial isolation on conventional L-J medium vs. the BACTEC system, and to
      determine the prevalence of multidrug resistance in cutaneous tuberculosis.
      METHODS: Thirty-five untreated, clinically diagnosed, and histopathologically
      documented patients with cutaneous tuberculosis constituted the study material.
      Lesional skin biopsy specimens were cultured on both L-J medium and the BACTEC
      system. The isolates obtained were identified and subjected to sensitivity to
      rifampicin, isoniazid, ethambutol, and streptomycin using the BACTEC system.
      RESULTS: Twenty-six mycobacterial isolates were recovered from 35 patients. Nine
      isolates (25.7%) grew on L-J medium after a mean period of 31.5 days, and 22
      (62.8%) on the BACTEC system in 17.3 days. All of the isolates were identified as
      Mycobacterium tuberculosis. Drug susceptibility testing demonstrated 12 isolates
      to be resistant, seven multidrug resistant. DISCUSSION: The BACTEC system
      demonstrated an improved mycobacterial isolation rate and substantially reduced
      detection time when compared with L-J medium. The combined isolation rate on both
      media was 74.3% (26/35), greater than that of either used separately. Drug
      resistance was observed in 46.2% of isolates. CONCLUSION: Radiometric liquid
      culture medium together with conventional L-J medium may be recommended in
      practice to enable the institution of appropriate antituberculous therapy
      modifications in drug-resistant cases of cutaneous tuberculosis.

PMID- 18613874
TI  - Clinical significance of dermoscopy in alopecia areata: analysis of 300 cases.
AB  - OBJECTIVE: To determine dermoscopic findings of alopecia areata (AA) from a large
      scale study that can be used as clinical indicators of disease. METHODS:
      Dermoscopic examination of areas of hair loss on the scalp of 300 Asian patients
      with AA was performed using a DermLite II pro, which can block light reflection
      from the skin surface without immersion gels. Using the Spearman rank-order
      correlation coefficient by rank test, correlations between the incidence of each
      dermoscopic finding and the severity of disease and disease activity were
      examined. The sensitivity and specificity of the findings as diagnostic clues for
      AA were evaluated. RESULTS: Characteristic dermoscopic findings of AA included
      black dots, tapering hairs, broken hairs, yellow dots, and clustered short vellus
      hairs (shorter than 10 mm) in the areas of hair loss. Black dots, yellow dots,
      and short vellus hairs correlated with the severity of disease, and black dots,
      tapering hairs, broken hairs, and short vellus hairs correlated with disease
      activity. For diagnosis, yellow dots and short vellus hairs were the most
      sensitive markers, and black dots, tapering hairs, and broken hairs were the most
      specific markers. CONCLUSION: Dermoscopic characteristics, such as black dots,
      tapering hairs, broken hairs, yellow dots, and clustered short vellus hairs, are
      useful clinical indicators for AA.

PMID- 18613875
TI  - Rhinosporidiosis: gigantic cells with engulfed sporangia of Rhinosporidium
      seeberi in the case of dermosporidiosis.
AB  - Rhinosporidiosis in an Indian male with a tumorous skin lesion is reported.
      Histopathology from the skin lesion revealed gigantic foreign body giant cells
      bloated with multiple, engulfed sporangia of rhinosporidiosis, which has not been
      reported earlier. The term "dermosporidiosis", should be used to denote such
      predominant skin lesions of rhinosporidiosis.

PMID- 18613876
TI  - Oral infection by Diptera larvae in children: a case report.
AB  - BACKGROUND: Oral myiasis is usually caused by flies of the order Diptera. One of
      the causes of human myiasis is Cochliomyia hominivorax, which is a true obligate
      parasite of mammals. METHODS: A case of oral myiasis in a 5-year-old girl is
      reported. She presented with a swelling on the hard palate accompanied by intense
      pain and a fetid odor. A literature review of oral myiasis reports in children
      was performed. RESULTS: The poor oral hygiene, lip incompetence, open bite, and
      residence in a rural area were considered to be predisposing factors for larval
      infestation in this patient. Treatment consisted of manual larval removal and
      systemic therapy with antimicrobials. CONCLUSIONS: The prevention of human
      myiasis should involve the control of fly populations and general cleanliness,
      such as reducing decomposition odors and cleaning and covering wounds. In
      addition, the public should be informed that individuals living in locations
      without basic sanitation are more predisposed to infestation.

PMID- 18613877
TI  - Cutaneous rhinosporidiosis presents with recurrent nasal philtrum mass in
      southern Turkey.
AB  - We report a case of cutaneous rhinosporidiosis localized in the nasal philtrum.
      The patient's complaints started 3 months prior to being seen in our clinics.
      Ear, nose, and throat examination showed the presence of a polypoid lesion
      filling the right nostril. Complete surgical resection of the polypoid lesion
      provided a temporary relief as the patient developed the same lesion atin 6 weeks
      post-operation. The appearance and the recurrence pattern have led us to
      determine whether this lesion was rhinosporidiosis. Histopathological examination
      confirmed rhinosporidiosis. Finally, we performed complete resection followed by
      cauterization of the base of the mass. The infection has been reported in hot,
      tropical climates, and endemic zones of India and Sri Lanka. To our knowledge
      there is no reported case of rhinosporidiosis from southern Turkey within the
      subtropical Mediterranean climatic area.

PMID- 18613878
TI  - Bizarre, polycyclic, circinate, and floral-patterned reversible depigmentation in
      a patient with chronic bullous disease of childhood.

PMID- 18613879
TI  - Granular parakeratosis.
AB  - A healthy 62-year-old woman was referred to our dermatology department with a 1
      month history of a pruritic axillary eruption. On examination, multiple
      erythematous and brownish hyperkeratotic papules were seen in both axillae. Some
      of these lesions coalesced into plaques, with small areas of sparing, and a
      background erythematous color was also found in the axillary vaults (Fig. 1).
      There was no involvement of other intertriginous sites and there were no
      associated systemic symptoms. The patient was not obese. The patient had removed
      the hair from her axillae with wax 3 weeks before the development of the
      eruption. Moreover, she had changed her antiperspirant 1 week before the onset of
      the lesions. A cutaneous biopsy for histologic analysis was performed.
      Histologically, the stratum corneum was thickened, with persistent nuclei
      together with countless small basophilic granules. The granular layer was
      preserved and, in some areas, hypergranulosis was found (Fig. 2). These findings
      were characteristic of granular parakeratosis. The cutaneous lesions resolved
      completely after 1 week of treatment with topical betamethasone dipropionate and
      gentamicin sulfate (twice daily). The patient was urged to discontinue her use of
      deodorants.

PMID- 18613880
TI  - Hypozincemia and hyperzincuria associated with necrolytic acral erythema.

PMID- 18613881
TI  - Dermoscopy: basic concepts.
AB  - Dermoscopy is a very useful technique for the analysis of pigmented skin lesions.
      It represents a link between clinical and histological views, permitting an
      earlier diagnosis of skin melanoma. It also helps in the diagnosis of many other
      pigmented skin lesions, such as seborrheic keratosis, pigmented basal cell
      carcinoma, hemangioma, blue nevus, atypical nevus, and mole, which can often
      clinically simulate melanoma. In this article, dermoscopy is reviewed from its
      history to the basic concepts of the interpretation of dermoscopic images. The
      goal is to introduce this subject to those not yet familiar with it, in order to
      instigate and encourage the training and practice of this technique of growing
      importance for everyday usage.

PMID- 18613882
TI  - Primary cutaneous T-cell lymphoma, unspecified, exhibiting an aggressive clinical
      course and a cytotoxic phenotype.

PMID- 18613883
TI  - Multiple eruptive dermatofibromas and immunosuppression: report of two cases and
      review of the literature.
AB  - Dermatofibromas are common benign fibrohistiocytic tumors that are most often
      solitary. The occurrence of multiple eruptive dermatofibromas (MEDF), on the
      contrary, is a rare event. MEDF have been reported in the setting of autoimmune
      diseases, treated with immunosuppressive drugs, in the course of HIV infection
      and in neoplastic diseases. An association with immunosuppression has led to the
      speculation that they are the result of an abortive immunoreactive process. Here,
      we describe a patient with Sezary syndrome and a patient with multiple IgA
      myeloma who developed MEDF. These associations have not been reported previously.

PMID- 18613885
TI  - Lichen striatus in adults and pimecrolimus: open, off-label clinical study.
AB  - BACKGROUND: Lichen striatus is a well-known, acquired, self-healing, linear
      inflammatory dermatosis. Lichen striatus occurring in adults tends to be more
      extensive and itchy than in children, sometimes requiring symptomatic treatment.
      The therapeutic approach usually adopted is topical steroids, even though
      prolonged use may lead to several side-effects, particularly cutaneous atrophy.
      OBJECTIVE: To report the results of an open, off-label study on the use of
      pimecrolimus 1% in the treatment of diffuse, nonresponsive forms of lichen
      striatus. METHODS: Three adult patients suffering from relapsing or disseminated
      and itchy lichen striatus received topical application of pimecrolimus 1% cream
      (Elidel, Novartis Pharma, Basle, Switzerland) twice daily for 6 weeks, or until
      complete disappearance of the cutaneous lesions. RESULTS: All patients
      experienced rapid healing of the dermatosis, without any recurrence for at least
      14 months. CONCLUSION: Our preliminary results show that pimecrolimus may
      represent a useful therapeutic alternative for lichen striatus, although further
      studies on a larger number of cases are needed to confirm its safety and efficacy
      in the treatment of this condition.

PMID- 18613884
TI  - Recurrent nodule on the nasal columella: a good reason to re-biopsy.
AB  - BACKGROUND: A 15-year-old Caucasian male presented with 9-month history of a
      recurrent nodule on the nasal columella. The previous biopsy was reported as a
      neurofibroma. METHODS: Frozen sections revealed a spindle cell neoplasm.
      Permanent section immunohistochemistry sections stained positive for vimentin and
      smooth muscle actin and negative for S100 and CD34, confirming the diagnosis of
      leiomyosarcoma. RESULTS: The tumor was removed using Mohs micrographic surgery.
      Radiological work-up revealed no distant metastasis. There has been no local
      recurrence to date. CONCLUSIONS: Leiomyosarcoma is a difficult diagnosis to make
      clinically and requires histological confirmation. Re-biopsy of a "benign" growth
      may be necessary if clinicopathological correlation does not match with the
      clinical behavior of the tumor in question. Finally, Mohs micrographic surgery is
      a useful treatment modality for leiomyosarcomas, particularly those located in
      cosmetically-sensitive regions of the body such as the nose.

PMID- 18613886
TI  - Prevention and treatment of glucocorticoid-induced osteoporosis in daily
      dermatologic practice.
AB  - BACKGROUND: Systemic glucocorticoids (GCs) are often needed to treat dermatologic
      patients. The long-term use of GCs, however, is associated with potentially
      severe side-effects. GC-induced osteoporosis (GIO) is one of the most serious
      complications, but the risk of the occurrence of GIO seems to be generally
      underestimated. AIM: To provide an update of the recent advances in the
      prevention of GIO in dermatologic practice. METHODS: Review of the literature and
      several European and US guidelines up to August 2007. RESULTS: Data regarding the
      prevention and treatment of GIO are limited and guidelines for the prevention of
      GIO are not fully consistent. CONCLUSION: The prophylaxis of osteoporosis needs
      to be started early during treatment with GCs. Calcium and vitamin D supplements
      in all patients on systemic GCs and bisphosphonates in patients who take GCs for
      more than 3 months are practical and effective measures.

PMID- 18613887
TI  - From basic research to the bedside: efficacy of topical treatment with
      pseudocatalase PC-KUS in 71 children with vitiligo.
AB  - BACKGROUND: The epidermal accumulation of hydrogen peroxide (H(2)O(2)) has been
      documented in vitiligo. AIM: To assess the effect on disease cessation and
      repigmentation of the reduction/removal of H(2)O(2) using low-dose, narrow-band,
      ultraviolet-B (UV-B)-activated pseudocatalase PC-KUS in 71 children with
      vitiligo. METHODS: This uncontrolled and retrospective study included 45 girls
      and 26 boys (mean age, 10.3 years) who applied topical PC-KUS twice daily to the
      entire body surface without narrow-band UV-B dose increments. The affected body
      areas were documented by special photography at the first visit and after 8-12
      months. The response was evaluated by two independent physicians as > 75% vs. <
      75% total repigmentation of the face/neck, trunk, extremities, and hands/feet.
      Generalized (n = 61) and segmental (n = 10) vitiligo were evaluated as different
      entities. The effect of total-body, low-dose, narrow-band UV-B (0.15 mJ/cm(2))
      monotherapy once daily without any increments and without application of PC-KUS
      was tested over 6 months in 10 children with vitiligo vulgaris (mean age, 8.4
      years). RESULTS: One hundred per cent cessation was observed in 70 of the 71
      children. More than 75% repigmentation was achieved in 66 of 71 patients on the
      face/neck, 48 of 61 on the trunk, and 40 of 55 on the extremities; however,
      repigmentation on the hands/feet was disappointing (five of 53). The response was
      independent of skin color, age of onset, duration of disease, other demographic
      features, and previous treatments. The follow-up after narrow-band UV-B
      monotherapy showed no significant repigmentation in all areas. Seven of 10
      patients showed progression of their vitiligo. CONCLUSION: A reduction in
      epidermal H(2)O(2) using low-dose, narrow-band UV-B-activated pseudocatalase PC
      KUS is an effective treatment for childhood vitiligo which can be safely
      performed at home.

PMID- 18613888
TI  - Eponyms of Sir Jonathan Hutchinson.
AB  - Sir Jonathan Hutchinson was an extraordinary man. He was trained as a surgeon and
      a pathologist, but was also keenly interested in dermatology, the study of
      syphilis, ophthalmology, and neurology. His observations with detailed
      descriptions of skin diseases were remarkable. His medical bibliography
      staggeringly consists of over 1000 published reports. This description of the
      eponyms attributed to Hutchinson--illustrated with clinical images, an old plate,
      and a portrait--demonstrates his important contribution to dermatology.

PMID- 18613889
TI  - Unusual evolution of giant porokeratosis developing in two renal transplant
      patients.

PMID- 18613890
TI  - Atypical petechial rash of the lower extremities due to Parvovirus B19 infection.

PMID- 18613891
TI  - A study of palmoplantar keratodermas in South India.

PMID- 18613892
TI  - Longitudinal melanonychia secondary to chromoblastomycosis due to Fonsecaea
      pedrosoi.

PMID- 18613893
TI  - Contact pemphigus: a side-effect of imiquimod therapy.

PMID- 18613894
TI  - A distinct cutaneous reaction to sorafenib and a multikinase inhibitor.

PMID- 18613895
TI  - Raising the profile of pneumococcal disease.

PMID- 18613896
TI  - Strengthening the scientific approach to clinical practice in the new physician
      training programme.

PMID- 18613897
TI  - Cardiovascular testing in Fabry disease: exercise capacity reduction,
      chronotropic incompetence and improved anaerobic threshold after enzyme
      replacement.
AB  - AIM: The aim of this study was to document exercise capacity and serial
      electrocardiogram and echocardiograph findings in a cohort of Australian patients
      with Fabry disease, in relation to their history of enzyme replacement therapy
      (ERT). BACKGROUND: Fabry disease has multifactorial effects on the cardiovascular
      system. Most previous studies have focused on electrocardiographic and
      echocardiographic parameters. Exercise capacity can be used as an integrated
      measure of cardiovascular function and allows the effects of treatment to be
      monitored. METHODS: A total of 38 patients (30 men and 8 women) with Fabry
      disease were monitored by 12-lead electrocardiograms every 6-12 months, and by
      annual standardized-protocol echocardiograms. Bicycle stress tests with VO(2) max
      measurement and once-only 6 minutes' walk tests were also carried out in subsets
      of patients whose general health status allowed testing. RESULTS: Seventy per
      cent of patients met electrocardiogram criteria for left ventricular hypertrophy.
      Left ventricular hypertrophy on echocardiograph was present in 64% of patients
      (80% of men). Exercise capacity was reduced in patients with Fabry disease
      compared with that predicted from normative population data. Mild improvement in
      anaerobic threshold was seen in the first year of ERT (14.1 +/- 3.0 to 15.8 +/-
      3.0, P = 0.02), but no consistent further increase was seen beyond the first
      year. Most patients had resting bradycardia, with impaired ability to increase
      heart rate during exercise. Serial testing on ERT showed an improvement in
      anaerobic threshold but no significant change in VO(2) max. CONCLUSIONS: Male
      patients with Fabry disease were unable to attain predicted maximal heart rate on
      exercise or to achieve normal exercise levels. ERT was associated with a small
      improvement in anaerobic threshold over the first year.

PMID- 18613898
TI  - Intravascular haemolysis in a patient on ceftriaxone with demonstration of
      anticeftriaxone antibodies.
AB  - Drug-induced haemolytic anaemia can be life threatening. We report a case of
      ceftriaxone-induced severe haemolytic anaemia in a previously healthy 68-year-old
      woman. The patient had a positive direct antiglobulin test (anti-C3d positive,
      anti-immunoglobulin G negative). Serological tests showed ceftriaxone-specific
      antibodies. The patient recovered after cessation of the drug. This complication
      may cause milder anaemia and thus be poorly recognized.

PMID- 18613899
TI  - Lessons from a review of thyroglobulin assays in the management of thyroid
      cancer.
AB  - Thyroglobulin (Tg) measurement has become increasingly an important and integral
      part of the follow up and management of patients with differentiated thyroid
      cancer. Clinicians predominantly rely on Tg for decision-making for surveillance
      of patients with differentiated thyroid cancer, but despite this new reliance,
      issues regarding Tg measurement have not been appropriately addressed especially
      within a local context. In the process of developing an institutional protocol we
      have identified that there are significant clinical and technical issues
      regarding Tg measurement, and surprisingly Tg assessment is currently not part of
      an external quality control programme. We conducted a small pilot study to
      specifically emphasize some of the assay issues. We aim to inform
      endocrinologists, pathologists and nuclear medicine physicians, the need and
      urgency for these issues to be addressed to improve the ongoing surveillance of
      differentiated thyroid cancer.

PMID- 18613900
TI  - Global climate change: time to mainstream health risks and their prevention on
      the medical research and policy agenda.
AB  - Climate change is unequivocal. The fourth assessment report of the
      Intergovermental Panel on Climate Change has recently projected that global
      average surface temperature will increase by 1.1 to 6.4 degrees C by 2100.
      Anthropogenic warming during the twenty-first century would be much greater than
      that observed in the twentieth century. Most of the warming observed over the
      last six decades is attributable to human activities. Climate change is already
      affecting, and will increasingly have profound effects on human health and well
      being. Therefore, there is an urgent need for societies to take both preemptive
      and adaptive actions to protect human populations from adverse health
      consequences of climate change. It is time to mainstream health risks and their
      prevention in relation to the effects of climate change on the medical research
      and policy agenda.

PMID- 18613901
TI  - Posterior mediastinal teratoma.

PMID- 18613902
TI  - Oropharyngeal tuberculosis.

PMID- 18613903
TI  - Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes in a 69
      year-old woman.

PMID- 18613904
TI  - Scurvy masquerading as infectious cellulitis [corrected].

PMID- 18613906
TI  - Older impaired doctors.

PMID- 18613907
TI  - Older impaired doctors.

PMID- 18613908
TI  - Advanced directive. Choice based on informed consent.

PMID- 18613909
TI  - Safety vs. privacy: elderly persons' experiences of a mobile safety alarm.
AB  - The demographic development indicates an increased elderly population in Sweden
      in the future. One of the greatest challenges for a society with an ageing
      population is to provide high-quality health and social care. New information and
      communication technology and services can be used to further improve health care.
      To enable elderly persons to stay at home as long as possible, various kinds of
      technology, such as safety alarms, are used at home. The aim of this study was to
      describe the experiences of elderly persons through testing a mobile safety alarm
      and their reasoning about safety, privacy and mobility. The mobile safety alarm
      tested was a prototype in development. Five elderly persons with functional
      limitations and four healthy elderly persons from a pensioner's organisation
      tested the alarm. The mobile alarm with a drop sensor and a positioning device
      was tested for 6 weeks. This intervention was evaluated with qualitative
      interviews, and analysed with latent content analysis. The result showed four
      main categories: feeling safe, being positioned and supervised, being mobile, and
      reflecting on new technology. From these categories, the overarching category
      'Safety and mobility are more important than privacy' emerged. The mobile safety
      alarm was perceived to offer an increased opportunity for mobility in terms of
      being more active and as an aid for self-determination. The fact that the
      informants were located by means of the positioning device was not experienced as
      violating privacy as long as they could decide how to use the alarm. It was
      concluded that this mobile safety alarm was experienced as a tool to be active
      and mobile. As a way to keep self-determination and empowerment, the individual
      has to make a 'cost-benefit' analysis where privacy is sacrificed to the benefit
      of mobility and safety. The participants were actively contributing to the
      development process.

PMID- 18613910
TI  - The impact of managed competition on diversity, innovation and creativity in the
      delivery of home-care services.
AB  - Reforming publicly funded healthcare systems by introducing elements of
      competition, often by allowing for-profit providers to compete with not-for
      profit providers, is a strategy that has become commonplace in Western
      democracies. It is widely thought that the competitive forces of the marketplace
      will lead to greater efficiency, diversity and even innovation in the delivery of
      services. Between 1997 and 2000, a model of 'managed competition' was introduced
      as a major reform to the delivery of home-care services in Ontario, Canada. It
      was expected that by allowing greater competition within the home-care sector,
      this model would constrain costs and encourage provider agencies to become more
      innovative and creative in meeting service delivery needs. The purpose of this
      case study is to explore the impact of the managed competition reform on the for
      profit and the not-for-profit organisations that provided rehabilitation home
      care services, and, more specifically, to assess the extent to which the goal of
      greater diversity, innovation and creativity was achieved following
      implementation of the reform. A purposive sample of 49 key informants were
      selected for in-depth interviews, and a survey of the 36 organisations that
      provided rehabilitation home-care services and the 43 community care access
      centres that purchased services from these provider agencies was conducted. Data
      were collected between November 2002 and May 2003. Findings demonstrate that a
      combination of coercive, mimetic and normative isomorphic pressures have
      constrained diversity, innovation and creativity within the home-care sector. The
      implication is that the features that have traditionally distinguished for-profit
      and not-for-profit provider agencies from each other are rapidly disappearing,
      and a new hybrid organisational structure is evolving.

PMID- 18613911
TI  - Quality of private personal care for elderly people with a disability living at
      home: correlates and potential outcomes.
AB  - To investigate correlates of the quality of private personal care for community
      dwelling elderly people, this cross-sectional study enrolled 100 elderly
      outpatients living at home, along with their private aides and 88 informal
      caregivers, from May 2005 to January 2007. Cases were stratified according to the
      quality of private care as was described by both elderly participants and
      informal caregivers. In cases where the elderly person was suffering from overt
      cognitive impairment, only the opinions of the informal caregivers were taken
      into account. A comparison was made between the 'poor or fair care' group (n =
      16), the 'intermediate care' group (n = 39) and the 'optimal care' group (n =
      45). Considering the characteristics of private aides, there was a significant
      trend across the three groups in terms of language skills (P = 0.002) and level
      of distress with life conditions (P = 0.020). A statistical analysis performed on
      elderly participants without an overt cognitive impairment (n = 59) and informal
      caregivers showed an increase in the European Quality of Life Visual Analogue
      Scale score in the elderly group [mean +/- standard deviation (SD) were,
      respectively, 45 +/- 23.2, 63.7 +/- 19.7 and 68.8 +/- 21.6; P = 0.007], and a
      decrease in the Caregiver Burden Inventory score (mean +/- SD were, respectively,
      34.9 +/- 25.3, 26 +/- 17.7 and 17.6 +/- 14.6; P = 0.020) across the three groups.
      We found no significant difference between elderly people in the three groups in
      terms of social variables, functional and cognitive status, prevalence of
      depressive disorders and morbidity. Therefore, good language skills and non
      distressing life conditions of private aides appeared to be correlates of an
      optimal quality of care for community-dwelling elderly people with a disability,
      and also a better quality of life for them and less distress for their informal
      caregivers appeared to be potential outcomes of the quality of personal care.

PMID- 18613912
TI  - Patients' experiences of a community pharmacy-led medicines management service.
AB  - Medicines management services provided by community pharmacists have been
      proposed as one means to ensure that patients receive all the medicines they may
      benefit from in the English National Health Service. These services may also
      offer ways of addressing the historic under-utilization of community pharmacists'
      clinical skills and expertise. Medicines management services differ significantly
      from the dispensing and medicines sales roles traditionally associated with
      community pharmacy, particularly in relation to the provision for pharmacists to
      make recommendations to both patients and doctors about pharmacological treatment
      and lifestyle management. This paper describes patients' experiences of a
      medicines management service provided by community pharmacists for people with
      coronary heart disease, delivered in England. It draws on findings from
      semistructured, face-to-face interviews with 49 patients recruited from pilot
      sites delivering the service. Findings suggest that although patients cautiously
      welcomed the opportunity to consult with a pharmacist about their medicines, they
      had reservations about them making recommendations about treatment, and many
      still regarded the doctor as the health professional 'in charge' of their
      medicines. The implications of these findings are discussed in light of the
      developing sociological literature on pharmacy and medicines usage.

PMID- 18613913
TI  - Residential status and depression among Korean elderly people: a comparison
      between residents of nursing home and those based in the community.
AB  - The purposes of this study were: (i) to compare the extent of depression in the
      nursing home and community-dwelling elderly people, and (ii) to find the
      variables including residential status and other related variables explaining
      depression in Korea. Two sets of secondary data were combined and used to achieve
      the objectives of this study. One data set relating to elderly people in nursing
      homes was from a part of 2002 Kyunggi Long-term Care System Construction Study by
      Kyunggi Research Institute, Kyunggi province, Korea. The other data set for
      community-dwelling elderly people was from a part of 2001 National Long-term Care
      Study by Korea Institute for Health and Social Affairs. The data set for this
      study included 307 elderly people living in nursing homes and 166 elderly people
      living in the community. Depression was measured and determined using the
      geriatric depression scale-short form (GDS-SF) Korean version, with scores of 8
      or higher to indicate possible depression. A total of 39.3%[95% confidence
      interval (CI); 32.1-46.9%] of the sample in the community elderly showed symptoms
      of depression, higher than the rate found in the nursing home elderly (24.0%)
      (95% CI; 19.5-29.2%). The mean (standard deviation) GDS-SF score for the elderly
      in the nursing home was 6.1 (3.4), and 7.4 (4.3) for elderly in the community,
      the difference being statistically significant [t (275.5) = -3.33; P < 001]. As a
      result of multiple logistic regression analysis, residential status has appeared
      as an important predictor after controlling other related variables. The adjusted
      odds ratio of depression associated with the nursing home residents in
      residential status, all other factors being equal, was 3.14 (95% CI; 1.30-7.58).
      Community-dwelling elderly people have higher odds of depression. These findings
      suggest that there is a need to provide adequate health-related care services for
      the elderly people in the community.

PMID- 18613924
TI  - Ki67 index in intracranial ependymoma: a promising histopathological candidate
      biomarker.
AB  - AIMS: The Ki67 tumour cell proliferation index is an independent prognostic
      factor in ependymoma patients. Essential prerequisites for validation of the Ki67
      index as a histopathological biomarker are the reproducibility of this factor and
      its prognostic influence by different observers (proof of objective clinical and
      analytical performance). To this end, the aim was to analyse systematically inter
      and intraobserver agreement and reproducibility of the prognostic impact of the
      Ki67 index in intracranial ependymoma. METHODS AND RESULTS: The study cohort
      contained 78 cases of intracranial ependymoma. In all cases, the Ki67 index was
      assessed by four experienced observers (EOs) and by four inexperienced observers
      (IOs) using the manual hot-spot method. There was considerable agreement on Ki67
      index assessment. There was higher observer agreement among EOs compared with
      IOs. For each observer, survival analysis showed significant association of low
      Ki67 index with favourable patient outcome. CONCLUSIONS: Our data show that the
      Ki67 index in intracranial ependymoma is a reproducible and robust prognostic
      factor and can be considered a promising histopathological candidate biomarker.
      Attainment of biomarker status requires further translational studies in the
      context of prospective therapeutic trials.

PMID- 18613925
TI  - Prolactin receptor expression in gynaecomastia and male breast carcinoma.
AB  - AIMS: Despite the well-established function of prolactin (PRL) in normal breast
      development, its role in breast cancer pathogenesis is still controversial. PRL
      activity is dependent on the activation of a transmembrane protein, the PRL
      receptor (PRLR). The aim was to evaluate and compare PRLR expression in
      gynaecomastia and male breast carcinoma (MBC). METHODS AND RESULTS: PRLR
      expression was detected immunohistochemically in 30 cases of gynaecomastia and 30
      cases of MBC. The whole series was also assessed for oestrogen receptors (ER),
      progesterone receptors (PR) and androgen receptors (AR). A cut-off of 10% was
      used as the criterion for positivity. Histological type and tumour
      differentiation were evaluated. Pathological stage was assessed [Tumour Node
      Metastasis (TNM)-International Union Against Cancer system]. Statistical analysis
      was performed with Fisher's exact test. PRLR positivity was seen in 20% of
      gynaecomastia cases and in 60% of MBC cases (P = 0.003). In gynaecomastia
      immunoreactivity was predominantly observed in luminal cell borders, whereas in
      MBC the reactivity was heterogeneous and mainly cytoplasmic. There was no
      statistically significant correlation between PRLR expression and ER, PR, AR,
      pTNM, or histological grade. CONCLUSIONS: PRLR is significantly more expressed in
      MBC than in gynaecomastia, and with different patterns of reactivity, suggesting
      a role for PRL in male breast carcinogenesis.

PMID- 18613926
TI  - Small round blue cell tumours: diagnostic and prognostic usefulness of the
      expression of B7-H3 surface molecule.
AB  - AIMS: To assess whether the expression of B7-H3 surface molecule could improve
      differential diagnosis of small cell round tumours. METHODS AND RESULTS: One
      hundred and one well-characterized paraffin-embedded small round cell tumours,
      stored in the pathology archive of the Gaslini Institute, were
      immunohistochemically analysed with the 5B14 monoclonal antibody, which
      recognizes the surface molecule B7-H3. All lymphoblastic lymphomas and the
      blastematous component of Wilms' tumours were completely negative and a few
      Ewing's sarcoma and Burkitt's lymphoma specimens showed focal positivity, whereas
      74% of neuroblastomas, 67% of rhabdomyosarcomas and 100% of medulloblastomas were
      positive. The pattern of immunoreactivity of 5B14 mAb observed in
      rhabdomyosarcoma, neuroblastoma and medulloblastoma specimens was limited to the
      cytoplasmic membrane, and in neuroblastomas areas of rosette formation or of
      ganglion differentiation were preferentially stained. Interestingly, in
      neuroblastoma patients high expression of the antigen recognized by the 5B14 mAb
      was associated with a worse event-free survival. CONCLUSIONS: The 5B14 mAb
      represents an additional tool for the differential diagnosis of small round cell
      tumours and might be useful in identifying neuroblastoma patients at risk of
      relapse who may take advantage of more careful follow-up.

PMID- 18613927
TI  - New guidelines--a golden opportunity.

PMID- 18613928
TI  - Continuing medical education in pediatric anesthesia--a theoretical overview.
AB  - The importance of continuing medical education (CME) as a method of improving the
      quality of care of children undergoing anesthesia is universally recognized. This
      article, which is based on a presentation at the FEAPA European Conference on
      Paediatric Anaesthesia in September 2007 in Amsterdam, gives a theoretical
      overview of continuing education and introduces some generic educational
      concepts, such as the CRISIS-criteria and Kirkpatrick's evaluation model, which
      are as relevant to pediatric anesthesia as to other areas of medical practice.
      The terms CME and continuing professional develop are described. Some
      consideration is given to how anesthesiologists can assess the potential worth of
      an educational activity for their practice. No attempt will be made to judge
      particular educational activities, as the choice of the most appropriate activity
      rests primarily with the individual.

PMID- 18613929
TI  - MAC-awake of sevoflurane in children.
AB  - INTRODUCTION: Age influences the potency of anesthetic agents, but there is
      little information on how age influences MAC-awake. MAC-awake may be an important
      aspect of anesthesia potency for the prevention of awareness during anesthesia.
      The aim of this study was to measure MAC-awake in a range of ages in children.
      METHODS: After institutional ethics approval and informed parental consent 60
      children were enrolled; 20 in each of three age groups (2 to <5, 5 to <8 and 8-12
      years). Children were excluded if they had opioids, sedative premedication or a
      procedure likely to cause any residual discomfort. All children had sevoflurane
      anesthesia. At the end of the procedure the sevoflurane was decreased to the
      target concentration. Once the target endtidal concentration was achieved it was
      maintained for 10 min before a standard stimulus was applied and an observer
      determined if the child was awake. The Dixon up-down method was used to determine
      progression of subsequent concentrations and MAC-awake (ED50) for the three age
      groups were obtained using the probit model. RESULTS: This study found evidence
      for a difference in ED50 between age groups (P = 0.008). The MAC-awake was
      highest in the youngest group (0.66%) and similar in the older groups (0.45% and
      0.43%). CONCLUSION: Although MAC-awake changes with age, in the ages where
      awareness has been reported, MAC-awake was found to be relatively low, and
      therefore it seems unlikely that age-specific changes to MAC-awake are a cause
      for awareness in children aged 5-12 years.

PMID- 18613930
TI  - Ketamine anesthesia in children--exploring infusion regimens.
AB  - AIM: We aimed to produce a racemic ketamine manual infusion regimen capable of
      maintaining a steady-state blood concentration associated with anesthesia in
      children aged 1.5-12 years. METHOD: The literature was searched for a ketamine
      blood concentration associated with anesthesia in humans. Pharmacokinetic
      parameter estimates were taken from published studies of infusion data in
      children and used in a pharmacokinetic simulation program to predict likely
      ketamine blood concentrations during infusions. A variability of 10% was allowed
      about the chosen target concentration. RESULTS: A target concentration of 3 mg.l(
      1) was chosen for simulation modeling. This target is greater than that
      associated with anesthesia when supplemented by nitrous oxide or midazolam in
      adults. Arousal to light touch or voice appears to occur at a mean plasma
      concentration of 0.5 mg.l(-1) in both children and adults. A loading dose of 2
      mg.kg(-1) followed by an infusion rate of 11 mg.kg(-1).h(-1) for the first 20
      min, 7 mg.kg(-1).h(-1) from 20 to 40 min, 5 mg.kg(-1).h(-1) from 40 to 60 min and
      4 mg.kg(-1).h(-1) from 1 to 2 h resulted in a steady-state target concentration
      of 3 mg.l(-1) in children 1.5-12 years. Arousal, either spontaneous or to speech,
      is anticipated 3 h 47 min after a 2 h infusion in an average 6-year-old child.
      The context sensitive half-time in children was shorter than in adults after 1.5
      h, rising from 30 min at 1 h to 55 min at 5 h after an infusion of 3 mg.kg(-1).h(
      1) in a 10 kg child. CONCLUSION: Children require higher infusion rates than
      adults to maintain steady-state concentrations of 3 mg.l(-1) and have shorter
      context sensitive half-times than adults after prolonged infusion. These
      differences can be attributed to age-related pharmacokinetics. We anticipate slow
      return to full consciousness after prolonged infusion, suggesting that a lower
      target concentration with supplementation from adjuvant short acting anesthetic
      drugs may be advantageous.

PMID- 18613931
TI  - Dexmedetomidine disposition in children: a population analysis.
AB  - BACKGROUND: There are few data describing dexmedetomidine population
      pharmacokinetics (PK) in children (0-15 years) despite increasing use. METHODS:
      An open-label study was undertaken to examine the PK of i.v. dexmedetomidine 1-4
      mug.kg(-1) bolus in children after cardiac surgery (n = 45). A population PK
      analysis of dexmedetomidine time-concentration profiles (148 observations) was
      undertaken using nonlinear mixed effects modeling. Estimates were standardized to
      a 70-kg adult using allometric size models. RESULTS: Children had a mean age of
      3.38 years (range 4 days to 14 years) and weight 15.1 kg (range 3.1-58.9 kg). A
      two-compartment disposition model with first order elimination was superior to a
      one-compartment model. Population parameter estimates (between subject
      variability) were clearance (CL) 39.2 (CV 30.36%) l.h(-1) per 70 kg, central
      volume of distribution (V1) 36.9 (69.49%) l per 70 kg, inter-compartment
      clearance (Q) 68.2 (37.6%) l.h(-1) per 70 kg and peripheral volume of
      distribution (V2) 69.9 (48.6%) l per 70 kg. Clearance at birth was 15.55 l.h(-1)
      per 70 kg and matured with a half-time of 46.5 weeks to reach 87% adult rate by 1
      year of age. Simulation of an infusion of 1 mug.kg(-1) over 10 min followed by an
      infusion of 0.7 mug.kg(-1).h(-1) for 50 min suggested that children arouse from
      sedation at a plasma concentration of 0.304 mug.l(-1). CONCLUSIONS: Clearance in
      neonates is approximately one-third of that described in adults, consistent with
      immature elimination pathways. Maintenance dosing, which is a function of
      clearance, should be reduced in neonates and infants when using a target
      concentration approach.

PMID- 18613932
TI  - Anaesthetic management of gastroschisis - a review of our practice over the past
      5 years.
AB  - BACKGROUND: Surgical closure of gastrochisis has traditionally been performed
      under general anesthesia followed by admission to intensive care and
      postoperative ventilation. We reviewed the management of these neonates in our
      hospital over the past 5 years to identify the changes in practice and possible
      factors which affect the peri-operative course. METHODS: We retrospectively
      identified cases of gastrochisis undergoing repair from June 2002 to May 2007.
      Details of the demographic data, preoperative factors, intra-operative anesthetic
      and surgical management, and postoperative care were collected from the
      anesthetic chart, operative record, and patient notes. RESULTS: Forty-eight self
      ventilating neonates underwent operative repair in theatre. A neuraxial local
      anesthetic block was performed as part of the anesthetic technique in 22
      patients. There was a significant difference in the need for postoperative
      ventilation in this group (23%) when compared with a traditional opioid-based
      method of providing analgesia (88%, P < 0.05). This difference was seen in both
      term and preterm babies. CONCLUSION: Conclusions are difficult to make when
      analyzing retrospective data in patients with a heterogeneous variety of factors.
      The results suggest that anesthesia which includes a regional technique is a
      valid method in these cases. Traditional opioid analgesia when compared with
      regional techniques may be associated with increased need for postoperative
      ventilation.

PMID- 18613933
TI  - Anatomic relationship between the internal jugular vein and the carotid artery in
      preschool children--an ultrasonographic study.
AB  - BACKGROUND: Central venous cannulation in young children is technically difficult
      and may lead to potentially serious complications especially when performed
      blindly or using anatomical landmarks only. AIM: The aim of this study was to
      determine the anatomical relationship of the internal jugular vein (IJV) and the
      common carotid artery (CA) in preschool children using ultrasound. METHODS: Forty
      five children aged 60 months and under were included prospectively and divided
      into three groups: group 1: <6 months, group 2: 7-18 months and group 3: 19-60
      months. With the head in neutral position the location of the left and right IJV
      was noted as anterior (A), anterolateral (AL), lateral (L) or medial (M) in
      relation to the CA at the level of the cricoid cartilage. Depths of IJV and CA as
      well as time taken to locate the vessels were recorded. RESULTS: The IJV was more
      commonly found in the AL position in all groups. The mean depth was 0.96 cm in
      group 1, 0.95 cm in group 2 and 3. Mean duration for localization of the vessels
      was 4.2 s in group 1, 4 s in group 2 and 4.3 s in group 3. The differences
      between the groups were not significant. CONCLUSION: This study demonstrates that
      the IJV cover the CA in the majority of young children. Depth of the IJV is
      rarely more than 1 cm deep to the skin. Ultrasound location of the IJV and CA is
      easy and does not necessarily delay the procedure. The findings of this study
      support the use of ultrasound guidance for CVC in children.

PMID- 18613934
TI  - The FLACC behavioral scale for procedural pain assessment in children aged 5-16
      years.
AB  - OBJECTIVES: To evaluate the concurrent and construct validity and the interrater
      reliability of the Face, Legs, Activity, Cry and Consolability (FLACC) scale
      during procedural pain in children aged 5-16 years. BACKGROUND: Self-reporting of
      pain is considered to be the primary source of information on pain intensity for
      older children but a validated observational tool will provide augment
      information to self-reports during painful procedures. METHODS: Eighty children
      scheduled for peripheral venous cannulation or percutaneous puncture of a venous
      port were included. In 40 cases two nurses simultaneously and independently
      assessed pain by using the FLACC scale and in 40 cases one of these nurses
      assessed the child. All children scored the intensity of pain by using the
      Coloured Analogue Scale (CAS) and distress by the Facial Affective Scale (FAS).
      RESULTS: Concurrent validity was supported by the correlation between FLACC
      scores and the children's self-reported CAS scores during the procedure (r =
      0.59, P < 0.05). A weaker correlation was found between the FLACC scores and
      children's self-reported FAS (r = 0.35, P < 0.05). Construct validity was
      demonstrated by the increase in median FLACC score to 1 during the procedure
      compared with 0 before and after the procedure (P < 0.001). Interrater
      reliability during the procedure was supported by adequate kappa statistics for
      all items and for the total FLACC scores (kappa = 0.85, P < 0.001). CONCLUSIONS:
      The findings of this study support the use of FLACC as a valid and reliable tool
      for assessing procedural pain in children aged 5-16 years.

PMID- 18613935
TI  - Management of an unusual pediatric difficult airway using ketamine as a sole
      agent.
AB  - We present the case of a 9-year-old boy who suffered a fall while brushing his
      teeth. This resulted in impalement of the lateral pharyngeal wall by the
      toothbrush with its head becoming firmly lodged adjacent to the internal carotid
      artery as demonstrated by CT scan. The length of the toothbrush protruding from
      the mouth and the inability to adequately assess the airway prior to any
      intervention gave rise to a unique set of surgical and anesthetic airway
      management problems. These were compounded by the possibility of damage to the
      carotid artery and potential catastrophic hemorrhage with manipulation of the
      toothbrush at any point. We detail the problems and outline our management.

PMID- 18613936
TI  - Anesthesia for a child with deletion 3q syndrome.

PMID- 18613937
TI  - Goldenhar syndrome and intubation with the fiberoptic broncoscope.

PMID- 18613938
TI  - Anesthesia in a child with massive thyroid enlargement.

PMID- 18613939
TI  - Intranasal clonidine as a premedicant: three cases with unique indications.

PMID- 18613940
TI  - YouTube in pediatric anesthesia induction.

PMID- 18613941
TI  - Anesthetic management for a child with mitochondrial complex II deficiency.

PMID- 18613942
TI  - Use of thromboelastography and hydroelectrolytic management in a child with
      chronic renal insufficiency submitted to liver transplantation secondary to type
      1 primary hyperoxaluria.

PMID- 18613943
TI  - Acute hypersensitivity reaction on re-exposure to basiliximab in an infant
      undergoing heart transplantation.

PMID- 18613945
TI  - A race through the maze of genomic evidence.

PMID- 18613946
TI  - A critical assessment of Mus musculus gene function prediction using integrated
      genomic evidence.
AB  - BACKGROUND: Several years after sequencing the human genome and the mouse genome,
      much remains to be discovered about the functions of most human and mouse genes.
      Computational prediction of gene function promises to help focus limited
      experimental resources on the most likely hypotheses. Several algorithms using
      diverse genomic data have been applied to this task in model organisms; however,
      the performance of such approaches in mammals has not yet been evaluated.
      RESULTS: In this study, a standardized collection of mouse functional genomic
      data was assembled; nine bioinformatics teams used this data set to independently
      train classifiers and generate predictions of function, as defined by Gene
      Ontology (GO) terms, for 21,603 mouse genes; and the best performing submissions
      were combined in a single set of predictions. We identified strengths and
      weaknesses of current functional genomic data sets and compared the performance
      of function prediction algorithms. This analysis inferred functions for 76% of
      mouse genes, including 5,000 currently uncharacterized genes. At a recall rate of
      20%, a unified set of predictions averaged 41% precision, with 26% of GO terms
      achieving a precision better than 90%. CONCLUSION: We performed a systematic
      evaluation of diverse, independently developed computational approaches for
      predicting gene function from heterogeneous data sources in mammals. The results
      show that currently available data for mammals allows predictions with both
      breadth and accuracy. Importantly, many highly novel predictions emerge for the
      38% of mouse genes that remain uncharacterized.

PMID- 18613947
TI  - Predicting gene function in a hierarchical context with an ensemble of
      classifiers.
AB  - BACKGROUND: The wide availability of genome-scale data for several organisms has
      stimulated interest in computational approaches to gene function prediction.
      Diverse machine learning methods have been applied to unicellular organisms with
      some success, but few have been extensively tested on higher level, multicellular
      organisms. A recent mouse function prediction project (MouseFunc) brought
      together nine bioinformatics teams applying a diverse array of methodologies to
      mount the first large-scale effort to predict gene function in the laboratory
      mouse. RESULTS: In this paper, we describe our contribution to this project, an
      ensemble framework based on the support vector machine that integrates diverse
      datasets in the context of the Gene Ontology hierarchy. We carry out a detailed
      analysis of the performance of our ensemble and provide insights into which
      methods work best under a variety of prediction scenarios. In addition, we
      applied our method to Saccharomyces cerevisiae and have experimentally confirmed
      functions for a novel mitochondrial protein. CONCLUSION: Our method consistently
      performs among the top methods in the MouseFunc evaluation. Furthermore, it
      exhibits good classification performance across a variety of cellular processes
      and functions in both a multicellular organism and a unicellular organism,
      indicating its ability to discover novel biology in diverse settings.

PMID- 18613948
TI  - GeneMANIA: a real-time multiple association network integration algorithm for
      predicting gene function.
AB  - BACKGROUND: Most successful computational approaches for protein function
      prediction integrate multiple genomics and proteomics data sources to make
      inferences about the function of unknown proteins. The most accurate of these
      algorithms have long running times, making them unsuitable for real-time protein
      function prediction in large genomes. As a result, the predictions of these
      algorithms are stored in static databases that can easily become outdated. We
      propose a new algorithm, GeneMANIA, that is as accurate as the leading methods,
      while capable of predicting protein function in real-time. RESULTS: We use a fast
      heuristic algorithm, derived from ridge regression, to integrate multiple
      functional association networks and predict gene function from a single process
      specific network using label propagation. Our algorithm is efficient enough to be
      deployed on a modern webserver and is as accurate as, or more so than, the
      leading methods on the MouseFunc I benchmark and a new yeast function prediction
      benchmark; it is robust to redundant and irrelevant data and requires, on
      average, less than ten seconds of computation time on tasks from these
      benchmarks. CONCLUSION: GeneMANIA is fast enough to predict gene function on-the
      fly while achieving state-of-the-art accuracy. A prototype version of a GeneMANIA
      based webserver is available at http://morrislab.med.utoronto.ca/prototype.

PMID- 18613949
TI  - Inferring mouse gene functions from genomic-scale data using a combined
      functional network/classification strategy.
AB  - The complete set of mouse genes, as with the set of human genes, is still largely
      uncharacterized, with many pieces of experimental evidence accumulating regarding
      the activities and expression of the genes, but the majority of genes as yet
      still of unknown function. Within the context of the MouseFunc competition, we
      developed and applied two distinct large-scale data mining approaches to infer
      the functions (Gene Ontology annotations) of mouse genes from experimental
      observations from available functional genomics, proteomics, comparative
      genomics, and phenotypic data. The two strategies - the first using classifiers
      to map features to annotations, the second propagating annotations from
      characterized genes to uncharacterized genes along edges in a network constructed
      from the features - offer alternative and possibly complementary approaches to
      providing functional annotations. Here, we re-implement and evaluate these
      approaches and their combination for their ability to predict the proper
      functional annotations of genes in the MouseFunc data set. We show that, when
      controlling for the same set of input features, the network approach generally
      outperformed a naive Bayesian classifier approach, while their combination offers
      some improvement over either independently. We make our observations of
      predictive performance on the MouseFunc competition hold-out set, as well as on a
      ten-fold cross-validation of the MouseFunc data. Across all 1,339 annotated genes
      in the MouseFunc test set, the median predictive power was quite strong (median
      area under a receiver operating characteristic plot of 0.865 and average
      precision of 0.195), indicating that a mining-based strategy with existing data
      is a promising path towards discovering mammalian gene functions. As one product
      of this work, a high-confidence subset of the functional mouse gene network was
      produced - spanning >70% of mouse genes with >1.6 million associations - that is
      predictive of mouse (and therefore often human) gene function and functional
      associations. The network should be generally useful for mammalian gene
      functional analyses, such as for predicting interactions, inferring functional
      connections between genes and pathways, and prioritizing candidate genes. The
      network and all predictions are available on the worldwide web.

PMID- 18613950
TI  - Consistent probabilistic outputs for protein function prediction.
AB  - In predicting hierarchical protein function annotations, such as terms in the
      Gene Ontology (GO), the simplest approach makes predictions for each term
      independently. However, this approach has the unfortunate consequence that the
      predictor may assign to a single protein a set of terms that are inconsistent
      with one another; for example, the predictor may assign a specific GO term to a
      given protein ('purine nucleotide binding') but not assign the parent term
      ('nucleotide binding'). Such predictions are difficult to interpret. In this
      work, we focus on methods for calibrating and combining independent predictions
      to obtain a set of probabilistic predictions that are consistent with the
      topology of the ontology. We call this procedure 'reconciliation'. We begin with
      a baseline method for predicting GO terms from a collection of data types using
      an ensemble of discriminative classifiers. We apply the method to a previously
      described benchmark data set, and we demonstrate that the resulting predictions
      are frequently inconsistent with the topology of the GO. We then consider 11
      distinct reconciliation methods: three heuristic methods; four variants of a
      Bayesian network; an extension of logistic regression to the structured case; and
      three novel projection methods - isotonic regression and two variants of a
      Kullback-Leibler projection method. We evaluate each method in three different
      modes - per term, per protein and joint - corresponding to three types of
      prediction tasks. Although the principal goal of reconciliation is
      interpretability, it is important to assess whether interpretability comes at a
      cost in terms of precision and recall. Indeed, we find that many apparently
      reasonable reconciliation methods yield reconciled probabilities with
      significantly lower precision than the original, unreconciled estimates. On the
      other hand, we find that isotonic regression usually performs better than the
      underlying, unreconciled method, and almost never performs worse; isotonic
      regression appears to be able to use the constraints from the GO network to its
      advantage. An exception to this rule is the high precision regime for joint
      evaluation, where Kullback-Leibler projection yields the best performance.

PMID- 18613951
TI  - Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces
      cerevisiae gene function.
AB  - BACKGROUND: Learning the function of genes is a major goal of computational
      genomics. Methods for inferring gene function have typically fallen into two
      categories: 'guilt-by-profiling', which exploits correlation between function and
      other gene characteristics; and 'guilt-by-association', which transfers function
      from one gene to another via biological relationships. RESULTS: We have developed
      a strategy ('Funckenstein') that performs guilt-by-profiling and guilt-by
      association and combines the results. Using a benchmark set of functional
      categories and input data for protein-coding genes in Saccharomyces cerevisiae,
      Funckenstein was compared with a previous combined strategy. Subsequently, we
      applied Funckenstein to 2,455 Gene Ontology terms. In the process, we developed
      2,455 guilt-by-profiling classifiers based on 8,848 gene characteristics and 12
      functional linkage graphs based on 23 biological relationships. CONCLUSION:
      Funckenstein outperforms a previous combined strategy using a common benchmark
      dataset. The combination of 'guilt-by-profiling' and 'guilt-by-association' gave
      significant improvement over the component classifiers, showing the greatest
      synergy for the most specific functions. Performance was evaluated by cross
      validation and by literature examination of the top-scoring novel predictions.
      These quantitative predictions should help prioritize experimental study of yeast
      gene functions.

PMID- 18613952
TI  - An en masse phenotype and function prediction system for Mus musculus.
AB  - BACKGROUND: Individual researchers are struggling to keep up with the
      accelerating emergence of high-throughput biological data, and to extract
      information that relates to their specific questions. Integration of accumulated
      evidence should permit researchers to form fewer - and more accurate - hypotheses
      for further study through experimentation. RESULTS: Here a method previously used
      to predict Gene Ontology (GO) terms for Saccharomyces cerevisiae (Tian et al.:
      Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces
      cerevisiae gene function. Genome Biol 2008, 9(Suppl 1):S7) is applied to predict
      GO terms and phenotypes for 21,603 Mus musculus genes, using a diverse collection
      of integrated data sources (including expression, interaction, and sequence-based
      data). This combined 'guilt-by-profiling' and 'guilt-by-association' approach
      optimizes the combination of two inference methodologies. Predictions at all
      levels of confidence are evaluated by examining genes not used in training, and
      top predictions are examined manually using available literature and knowledge
      base resources. CONCLUSION: We assigned a confidence score to each gene/term
      combination. The results provided high prediction performance, with nearly every
      GO term achieving greater than 40% precision at 1% recall. Among the 36 novel
      predictions for GO terms and 40 for phenotypes that were studied manually, >80%
      and >40%, respectively, were identified as accurate. We also illustrate that a
      combination of 'guilt-by-profiling' and 'guilt-by-association' outperforms either
      approach alone in their application to M. musculus.

PMID- 18613953
TI  - Determinants of neonatal mortality in Indonesia.
AB  - BACKGROUND: Neonatal mortality accounts for almost 40 per cent of under-five
      child mortality, globally. An understanding of the factors related to neonatal
      mortality is important to guide the development of focused and evidence-based
      health interventions to prevent neonatal deaths. This study aimed to identify the
      determinants of neonatal mortality in Indonesia, for a nationally representative
      sample of births from 1997 to 2002. METHODS: The data source for the analysis was
      the 2002-2003 Indonesia Demographic and Health Survey from which survival
      information of 15,952 singleton live-born infants born between 1997 and 2002 was
      examined. Multilevel logistic regression using a hierarchical approach was
      performed to analyze the factors associated with neonatal deaths, using
      community, socio-economic status and proximate determinants. RESULTS: At the
      community level, the odds of neonatal death was significantly higher for infants
      from East Java (OR = 5.01, p = 0.00), and for North, Central and Southeast
      Sulawesi and Gorontalo combined (OR = 3.17, p = 0.03) compared to the lowest
      neonatal mortality regions of Bali, South Sulawesi and Jambi provinces. A
      progressive reduction in the odds was found as the percentage of deliveries
      assisted by trained delivery attendants in the cluster increased. The odds of
      neonatal death were higher for infants born to both mother and father who were
      employed (OR = 1.84, p = 0.00) and for infants born to father who were unemployed
      (OR = 2.99, p = 0.02). The odds were also higher for higher rank infants with a
      short birth interval (OR = 2.82, p = 0.00), male infants (OR = 1.49, p = 0.01),
      smaller than average-sized infants (OR = 2.80, p = 0.00), and infant's whose
      mother had a history of delivery complications (OR = 1.81, p = 0.00). Infants
      receiving any postnatal care were significantly protected from neonatal death (OR
      = 0.63, p = 0.03). CONCLUSION: Public health interventions directed at reducing
      neonatal death should address community, household and individual level factors
      which significantly influence neonatal mortality in Indonesia. Low birth weight
      and short birth interval infants as well as perinatal health services factors,
      such as the availability of skilled birth attendance and postnatal care
      utilization should be taken into account when planning the interventions to
      reduce neonatal mortality in Indonesia.

PMID- 18613954
TI  - Oxygen dependence of metabolic fluxes and energy generation of Saccharomyces
      cerevisiae CEN.PK113-1A.
AB  - BACKGROUND: The yeast Saccharomyces cerevisiae is able to adjust to external
      oxygen availability by utilizing both respirative and fermentative metabolic
      modes. Adjusting the metabolic mode involves alteration of the intracellular
      metabolic fluxes that are determined by the cell's multilevel regulatory network.
      Oxygen is a major determinant of the physiology of S. cerevisiae but
      understanding of the oxygen dependence of intracellular flux distributions is
      still scarce. RESULTS: Metabolic flux distributions of S. cerevisiae CEN.PK113-1A
      growing in glucose-limited chemostat cultures at a dilution rate of 0.1 h-1 with
      20.9%, 2.8%, 1.0%, 0.5% or 0.0% O2 in the inlet gas were quantified by 13C-MFA.
      Metabolic flux ratios from fractional [U-13C]glucose labelling experiments were
      used to solve the underdetermined MFA system of central carbon metabolism of S.
      cerevisiae.While ethanol production was observed already in 2.8% oxygen, only
      minor differences in the flux distribution were observed, compared to fully
      aerobic conditions. However, in 1.0% and 0.5% oxygen the respiratory rate was
      severely restricted, resulting in progressively reduced fluxes through the TCA
      cycle and the direction of major fluxes to the fermentative pathway. A
      redistribution of fluxes was observed in all branching points of central carbon
      metabolism. Yet only when oxygen provision was reduced to 0.5%, was the biomass
      yield exceeded by the yields of ethanol and CO2. Respirative ATP generation
      provided 59% of the ATP demand in fully aerobic conditions and still a
      substantial 25% in 0.5% oxygenation. An extensive redistribution of fluxes was
      observed in anaerobic conditions compared to all the aerobic conditions. Positive
      correlation between the transcriptional levels of metabolic enzymes and the
      corresponding fluxes in the different oxygenation conditions was found only in
      the respirative pathway. CONCLUSION: 13C-constrained MFA enabled quantitative
      determination of intracellular fluxes in conditions of different redox challenges
      without including redox cofactors in metabolite mass balances. A redistribution
      of fluxes was observed not only for respirative, respiro-fermentative and
      fermentative metabolisms, but also for cells grown with 2.8%, 1.0% and 0.5%
      oxygen. Although the cellular metabolism was respiro-fermentative in each of
      these low oxygen conditions, the actual amount of oxygen available resulted in
      different contributions through respirative and fermentative pathways.

PMID- 18613955
TI  - Seat belt use among rear passengers: validity of self-reported versus
      observational measures.
AB  - BACKGROUND: The effects of seat belt laws and public education campaigns on seat
      belt use are assessed on the basis of observational or self-reported data on seat
      belt use. Previous studies focusing on front seat occupants have shown that self
      reports indicate a greater seat belt usage than observational findings. Whether
      this over-reporting in self reports applies to rear seat belt usage, and to what
      extent, have yet to be investigated. We aimed to evaluate the over-reporting
      factor for rear seat passengers and whether this varies by gender and under
      different compulsory seat belt use conditions. METHODS: The study was conducted
      in the Veneto Region, an area in the North-East of Italy with a population of 4.7
      million. The prevalence of seat belt use among rear seat passengers was
      determined by means of a cross-sectional self-report survey and an observational
      study. Both investigations were performed in two time periods: in 2003, when rear
      seat belt use was not enforced by primary legislation, and in 2005, after rear
      seat belt use had become compulsory (June 2003). Overall, 8138 observations and
      7902 interviews were recorded. Gender differences in the prevalence of rear seat
      belt use were examined using the chi-square test. The over-reporting factor,
      defined as the ratio of the self-reported to the observed prevalence of rear seat
      belt use, was calculated by gender before and after the rear seat belt
      legislation came into effect. RESULTS: Among rear seat passengers, self-reported
      rates were always higher than the observational findings, with an overall over
      reporting factor of 1.4. We registered no statistically significant changes over
      time in the over-reporting factor, nor any major differences between genders.
      CONCLUSION: Self-reported seat belt usage by rear passengers represents an
      efficient alternative to observational studies for tracking changes in actual
      behavior, although the reported figures need to be adjusted using an appropriate
      over-reporting factor in order to gain an idea of genuine seat belt use.

PMID- 18613956
TI  - Implication of TRIM alpha and TRIMCyp in interferon-induced anti-retroviral
      restriction activities.
AB  - BACKGROUND: TRIM5 alpha is a restriction factor that interferes with retroviral
      infections in a species-specific manner in primate cells. Although TRIM5 alpha is
      constitutively expressed, its expression has been shown to be up-regulated by
      type I interferon (IFN). Among primates, a particular case exists in owl monkey
      cells, which express a fusion protein between TRIM5 and cyclophilin A, TRIMCyp,
      specifically interfering with HIV-1 infection. No studies have been conducted so
      far concerning the possible induction of TRIMCyp by IFN. We investigated the
      consequences of IFN treatment on retroviral restriction in diverse primate cells
      and evaluated the implication of TRIM5 alpha or TRIMCyp in IFN-induced anti
      retroviral activities. RESULTS: First, we show that human type I IFN can enhance
      TRIM5 alpha expression in human, African green monkey and macaque cells, as well
      as TRIMCyp expression in owl monkey cells. In TRIM5 alpha-expressing primate cell
      lines, type I IFN has little or no effect on HIV-1 infection, whereas it
      potentiates restriction activity against N-MLV in human and African green monkey
      cells. In contrast, type I IFN treatment of owl monkey cells induces a great
      enhancement of HIV-1 restriction, as well as a strain-tropism independent
      restriction of MLV. We were able to demonstrate that TRIM5 alpha is the main
      mediator of the IFN-induced activity against N-MLV in human and African green
      monkey cells, whereas TRIMCyp mediates the IFN-induced HIV-1 restriction
      enhancement in owl monkey cells. In contrast, the type I IFN-induced anti-MLV
      restriction in owl monkey cells is independent of TRIMCyp expression. CONCLUSION:
      Together, our observations indicate that both TRIM5 alpha and TRIMCyp are
      implicated in IFN-induced anti-retroviral response in primate cells. Furthermore,
      we found that type I IFN also induces a TRIMCyp-independent restriction activity
      specific to MLV in owl monkey cells.

PMID- 18613958
TI  - The second chance story of HIV-1 DNA: Unintegrated? Not a problem!
AB  - Accumulation of high levels of unintegrated viral DNA is a common feature of
      retroviral infection. It was recently discovered that coinfection of cells with
      integrated and unintegrated HIV-1 can result in complementation, allowing viral
      replication in the absence of integration. This new mode of HIV-1 replication has
      numerous implications for the function of unintegrated viral DNA and its
      application as a therapeutic vector.

PMID- 18613957
TI  - Viral complementation allows HIV-1 replication without integration.
AB  - BACKGROUND: The integration of HIV-1 DNA into cellular chromatin is required for
      high levels of viral gene expression and for the production of new virions.
      However, the majority of HIV-1 DNA remains unintegrated and is generally
      considered a replicative dead-end. A limited amount of early gene expression from
      unintegrated DNA has been reported, but viral replication does not proceed
      further in cells which contain only unintegrated DNA. Multiple infection of cells
      is common, and cells that are productively infected with an integrated provirus
      frequently also contain unintegrated HIV-1 DNA. Here we examine the influence of
      an integrated provirus on unintegrated HIV-1 DNA (uDNA). RESULTS: We employed
      reporter viruses and quantitative real time PCR to examine gene expression and
      virus replication during coinfection with integrating and non-integrating HIV-1.
      Most cells which contained only uDNA displayed no detected expression from
      fluorescent reporter genes inserted into early (Rev-independent) and late (Rev
      dependent) locations in the HIV-1 genome. Coinfection with an integrated provirus
      resulted in a several fold increase in the number of cells displaying uDNA early
      gene expression and efficiently drove uDNA into late gene expression. We found
      that coinfection generates virions which package and deliver uDNA-derived genomes
      into cells; in this way uDNA completes its replication cycle by viral
      complementation. uDNA-derived genomes undergo recombination with the integrated
      provirus-derived genomes during second round infection. CONCLUSION: This novel
      mode of retroviral replication allows survival of viruses which would otherwise
      be lost because of a failure to integrate, amplifies the effective amount of
      cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the
      opportunity for diversification through errors of polymerization and
      recombination.

PMID- 18613959
TI  - A randomized controlled trial to evaluate self-determination theory for exercise
      adherence and weight control: rationale and intervention description.
AB  - BACKGROUND: Research on the motivational model proposed by Self-Determination
      Theory (SDT) provides theoretically sound insights into reasons why people adopt
      and maintain exercise and other health behaviors, and allows for a meaningful
      analysis of the motivational processes involved in behavioral self-regulation.
      Although obesity is notoriously difficult to reverse and its recidivism is high,
      adopting and maintaining a physically active lifestyle is arguably the most
      effective strategy to counteract it in the long-term. The purposes of this study
      are twofold: i) to describe a 3-year randomized controlled trial (RCT) aimed at
      testing a novel obesity treatment program based on SDT, and ii) to present the
      rationale behind SDT's utility in facilitating and explaining health behavior
      change, especially physical activity/exercise, during obesity treatment. METHODS:
      Study design, recruitment, inclusion criteria, measurements, and a detailed
      description of the intervention (general format, goals for the participants,
      intervention curriculum, and main SDT strategies) are presented. The intervention
      consists of a 1-year group behavioral program for overweight and moderately obese
      women, aged 25 to 50 (and pre-menopausal), recruited from the community at large
      through media advertisement. Participants in the intervention group meet weekly
      or bi-weekly with a multidisciplinary intervention team (30 2 h sessions in
      total), and go through a program covering most topics considered critical for
      successful weight control. These topics and especially their delivery were
      adapted to comply with SDT and Motivational Interviewing guidelines. Comparison
      group receive a general health education curriculum. After the program, all
      subjects are follow-up for a period of 2 years. DISCUSSION: Results from this RCT
      will contribute to a better understanding of how motivational characteristics,
      particularly those related to physical activity/exercise behavioral self
      regulation, influence treatment success, while exploring the utility of Self
      Determination Theory for promoting health behavior change in the context of
      obesity. TRIAL REGISTRATION: Clinical Trials Gov. Identifier NCT00513084.

PMID- 18613960
TI  - Attitudes toward psychopharmacology among hospitalized patients from diverse
      ethno-cultural backgrounds.
AB  - BACKGROUND: Biological factors influencing individual response to drugs are being
      extensively studied in psychiatry. Strikingly, there are few studies addressing
      social and cultural differences in attitudes toward psychotropic medications. The
      objective of this study was to investigate ethno-culturally determined beliefs,
      expectations and attitudes toward medication among a sample of hospitalized
      psychiatric patients. METHODS: An ad hoc questionnaire was designed to assess
      patients' expectations, attitudes and prejudice toward medication. The study
      included 100 adult patients hospitalized in Geneva, Switzerland. RESULTS:
      Patients were in majority male (63%), originated from Switzerland (54%) and spoke
      the local language fluently (93%). They took on the average 3 different
      psychotropic drugs. Sixty-eight percent of patients expected side effects and 60%
      were ready to stop medication because of them. Thirty percent of patients
      expected negative personal changes with treatment and 34% thought that their
      mental disorder could have been treated without drugs. Thirty six percent of the
      sample used alternative or complementary medicines. 35% of immigrant patients
      believed that medication had different effects on them than on local patients.
      When compared with Swiss patients, they more often reported that significant
      others had an opinion about medication (p = 0.041) and more frequently valued
      information provided by other patients about treatment (p = 0.010). CONCLUSION:
      Patients' attitudes toward medication should be investigated in clinical
      practice, as specific expectations and prejudice exist. Targeted interventions,
      especially for immigrant patients, might improve adherence.

PMID- 18613961
TI  - Asking the right questions: scoping studies in the commissioning of research on
      the organisation and delivery of health services.
AB  - Scoping studies have been used across a range of disciplines for a wide variety
      of purposes. However, their value is increasingly limited by a lack of definition
      and clarity of purpose. The UK's Service Delivery and Organisation Research
      Programme (SDO) has extensive experience of commissioning and using such studies;
      twenty four have now been completed.This review article has four objectives; to
      describe the nature of the scoping studies that have been commissioned by the SDO
      Programme; to consider the impact of and uses made of such studies; to provide
      definitions for the different elements that may constitute a scoping study; and
      to describe the lessons learnt by the SDO Programme in commissioning scoping
      studies.Scoping studies are imprecisely defined but usually consist of one or
      more discrete components; most commonly they are non-systematic reviews of the
      literature, but other important elements are literature mapping, conceptual
      mapping and policy mapping. Some scoping studies also involve consultations with
      stakeholders including the end users of research.Scoping studies have been used
      for a wide variety of purposes, although a common feature is to identify
      questions and topics for future research. The reports of scoping studies often
      have an impact that extends beyond informing research commissioners about future
      research areas; some have been published in peer reviewed journals, and others
      have been published in research summaries aimed at a broader audience of health
      service managers and policymakers.Key lessons from the SDO experience are the
      need to relate scoping studies to a particular health service context; the need
      for scoping teams to be multi-disciplinary and to be given enough time to
      integrate diverse findings; and the need for the research commissioners to be
      explicit not only about the aims of scoping studies but also about their intended
      uses. This necessitates regular contact between researchers and
      commissioners.Scoping studies are an essential element in the portfolio of
      approaches to research, particularly as a mechanism for helping research
      commissioners and policy makers to ask the right questions. Their utility will be
      further enhanced by greater recognition of the individual components, definitions
      for which are provided.

PMID- 18613962
TI  - Reduction of transmission from malaria patients by artemisinin combination
      therapies: a pooled analysis of six randomized trials.
AB  - BACKGROUND: Artemisinin combination therapies (ACT), which are increasingly being
      introduced for treatment of Plasmodium falciparum malaria, are more effective
      against sexual stage parasites (gametocytes) than previous first-line
      antimalarials and therefore have the potential to reduce parasite transmission.
      The size of this effect is estimated in symptomatic P. falciparum infections.
      METHODS: Data on 3,174 patients were pooled from six antimalarial trials
      conducted in The Gambia and Kenya. Multivariable regression was used to
      investigate the role of ACT versus non-artemisinin antimalarial treatment,
      treatment failure, presence of pre-treatment gametocytes and submicroscopic
      gametocytaemia on transmission to mosquitoes and the area under the curve (AUC)
      of gametocyte density during the 28 days of follow up. RESULTS: ACT treatment was
      associated with a significant reduction in the probability of being
      gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26),
      transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito
      infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means
      0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the
      difference between ACT and non-artemisinin impact. The presence of slide-positive
      gametocytaemia prior to treatment significantly reduced ACT impact on
      gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia
      reduced estimates of ACT impact in a high transmission setting in Kenya, but not
      in a lower transmission setting in the Gambia. CONCLUSION: Treatment with ACT
      significantly reduces infectiousness of individual patients with uncomplicated
      falciparum malaria compared to previous first line treatments. Rapid treatment of
      cases before gametocytaemia is well developed may enhance the impact of ACT on
      transmission.

PMID- 18613963
TI  - A broad spectrum, one-step reverse-transcription PCR amplification of the
      neuraminidase gene from multiple subtypes of influenza A virus.
AB  - BACKGROUND: The emergence of high pathogenicity strains of Influenza A virus in a
      variety of human and animal hosts, with wide geographic distribution, has
      highlighted the importance of rapid identification and subtyping of the virus for
      outbreak management and treatment. Type A virus can be classified into subtypes
      according to the viral envelope glycoproteins, hemagglutinin and neuraminidase.
      Here we review the existing specificity and amplification of published primers to
      subtype neuraminidase genes and describe a new broad spectrum primer pair that
      can detect all 9 neuraminidase subtypes. RESULTS: Bioinformatic analysis of 3,337
      full-length influenza A neuraminidase segments in the NCBI database revealed semi
      conserved regions not previously targeted by primers. Two degenerate primers with
      M13 tags, NA8F-M13 and NA10R-M13 were designed from these regions and used to
      generate a 253 bp cDNA product. One-step RT-PCR testing was successful in 31/32
      (97%) cases using a touchdown protocol with RNA from over 32 different cultured
      influenza A virus strains representing the 9 neuraminidase subtypes. Frozen
      blinded clinical nasopharyngeal aspirates were also assayed and were mostly of
      subtype N2. The region amplified was direct sequenced and then used in database
      searches to confirm the identity of the template RNA. The RT-PCR fragment
      generated includes one of the mutation sites related to oseltamivir resistance,
      H274Y. CONCLUSION: Our one-step RT-PCR assay followed by sequencing is a rapid,
      accurate, and specific method for detection and subtyping of different
      neuraminidase subtypes from a range of host species and from different
      geographical locations.

PMID- 18613964
TI  - Susceptibility to glaucoma: differential comparison of the astrocyte
      transcriptome from glaucomatous African American and Caucasian American donors.
AB  - BACKGROUND: Epidemiological and genetic studies indicate that ethnic/genetic
      background plays an important role in susceptibility to primary open angle
      glaucoma (POAG). POAG is more prevalent among the African-descent population
      compared to the Caucasian population. Damage in POAG occurs at the level of the
      optic nerve head (ONH) and is mediated by astrocytes. Here we investigated
      differences in gene expression in primary cultures of ONH astrocytes obtained
      from age-matched normal and glaucomatous donors of Caucasian American (CA) and
      African American (AA) populations using oligonucleotide microarrays. RESULTS:
      Gene expression data were obtained from cultured astrocytes representing 12
      normal CA and 12 normal AA eyes, 6 AA eyes with POAG and 8 CA eyes with POAG.
      Data were normalized and significant differential gene expression levels detected
      by using empirical Bayesian shrinkage moderated t-statistics. Gene Ontology
      analysis and networks of interacting proteins were constructed using the BioGRID
      database. Network maps included regulation of myosin, actin, and protein
      trafficking. Real-time RT-PCR, western blots, ELISA, and functional assays
      validated genes in the networks. CONCLUSION: Cultured AA and CA glaucomatous
      astrocytes retain differential expression of genes that promote cell motility and
      migration, regulate cell adhesion, and are associated with structural tissue
      changes that collectively contribute to neural degeneration. Key upregulated
      genes include those encoding myosin light chain kinase (MYLK), transforming
      growth factor-beta receptor 2 (TGFBR2), rho-family GTPase-2 (RAC2), and versican
      (VCAN). These genes along with other differentially expressed components of
      integrated networks may reflect functional susceptibility to chronic elevated
      intraocular pressure that is enhanced in the optic nerve head of African
      Americans.

PMID- 18613966
TI  - A unified approach to false discovery rate estimation.
AB  - BACKGROUND: False discovery rate (FDR) methods play an important role in
      analyzing high-dimensional data. There are two types of FDR, tail area-based FDR
      and local FDR, as well as numerous statistical algorithms for estimating or
      controlling FDR. These differ in terms of underlying test statistics and
      procedures employed for statistical learning. RESULTS: A unifying algorithm for
      simultaneous estimation of both local FDR and tail area-based FDR is presented
      that can be applied to a diverse range of test statistics, including p-values,
      correlations, z- and t-scores. This approach is semipararametric and is based on
      a modified Grenander density estimator. For test statistics other than p-values
      it allows for empirical null modeling, so that dependencies among tests can be
      taken into account. The inference of the underlying model employs truncated
      maximum-likelihood estimation, with the cut-off point chosen according to the
      false non-discovery rate. CONCLUSION: The proposed procedure generalizes a number
      of more specialized algorithms and thus offers a common framework for FDR
      estimation consistent across test statistics and types of FDR. In comparative
      study the unified approach performs on par with the best competing yet more
      specialized alternatives. The algorithm is implemented in R in the "fdrtool"
      package, available under the GNU GPL from
      http://strimmerlab.org/software/fdrtool/ and from the R package archive CRAN.

PMID- 18613965
TI  - EVI1 activation in blast crisis CML due to juxtaposition to the rare 17q22
      partner region as part of a 4-way variant translocation t(9;22).
AB  - BACKGROUND: Variant translocations t(9;22) occur in 5 to 10% of newly diagnosed
      CMLs and additional genetic changes are present in 60-80% of patients in blast
      crisis (BC). Here, we report on a CML patient in blast crisis presenting with a
      four-way variant t(9;22) rearrangement involving the EVI1 locus. METHODS: Dual
      colour Fluorescence In Situ Hybridisation was performed to unravel the different
      cytogenetic aberrations. Expression levels of EVI1 and BCR/ABL1 were investigated
      using real-time quantitative RT-PCR. RESULTS: In this paper we identified a
      patient with a complex 4-way t(3;9;17;22) which, in addition to BCR/ABL1 gene
      fusion, also resulted in EVI1 rearrangement and overexpression. CONCLUSION: This
      report illustrates how a variant t(9;22) translocation can specifically target a
      second oncogene most likely contributing to the more aggressive phenotype of the
      disease. Molecular analysis of such variants is thus warranted to understand the
      phenotypic consequences and to open the way for combined molecular therapies in
      order to tackle the secondary oncogenic effect which is unresponsive to imatinib
      treatment.

PMID- 18613967
TI  - Natriuretic peptides modify Pseudomonas fluorescens cytotoxicity by regulating
      cyclic nucleotides and modifying LPS structure.
AB  - BACKGROUND: Nervous tissues express various communication molecules including
      natriuretic peptides, i.e. Brain Natriuretic Peptide (BNP) and C-type Natriuretic
      Peptide (CNP). These molecules share structural similarities with cyclic
      antibacterial peptides. CNP and to a lesser extent BNP can modify the
      cytotoxicity of the opportunistic pathogen Pseudomonas aeruginosa. The
      psychrotrophic environmental species Pseudomonas fluorescens also binds to and
      kills neurons and glial cells, cell types that both produce natriuretic peptides.
      In the present study, we investigated the sensitivity of Pseudomonas fluorescens
      to natriuretic peptides and evaluated the distribution and variability of
      putative natriuretic peptide-dependent sensor systems in the Pseudomonas genus.
      RESULTS: Neither BNP nor CNP modified P. fluorescens MF37 growth or
      cultivability. However, pre-treatment of P. fluorescens MF37 with BNP or CNP
      provoked a decrease of the apoptotic effect of the bacterium on glial cells and
      an increase of its necrotic activity. By homology with eukaryotes, where
      natriuretic peptides act through receptors coupled to cyclases, we observed that
      cell-permeable stable analogues of cyclic AMP (dbcAMP) and cyclic GMP (8BcGMP)
      mimicked the effect of BNP and CNP on bacteria. Intra-bacterial concentrations of
      cAMP and cGMP were measured to study the involvement of bacterial cyclases in the
      regulation of P. fluorescens cytotoxicity by BNP or CNP. BNP provoked an increase
      (+49%) of the cAMP concentration in P. fluorescens, and CNP increased the intra
      bacterial concentrations of cGMP (+136%). The effect of BNP and CNP on the
      virulence of P. fluorescens was independent of the potential of the bacteria to
      bind to glial cells. Conversely, LPS extracted from MF37 pre-treated with dbcAMP
      showed a higher necrotic activity than the LPS from untreated or 8BcGMP-pre
      treated bacteria. Capillary electrophoresis analysis suggests that these
      different effects of the LPS may be due, at least in part, to variations in the
      structure of the macromolecule. CONCLUSION: These observations support the
      hypothesis that P. fluorescens responds to natriuretic peptides through a
      putative sensor system coupled to a cyclase that could interfere with LPS
      synthesis and thereby modify the overall virulence of the micro-organism.

PMID- 18613969
TI  - Aberrant right subclavian artery and calcified aneurysm of Kommerell's
      diverticulum: an alternative approach.
AB  - We report a 72 year-old man with dysphagia and dizziness. Aortography and
      Computed tomographic scans revealed the aberrant right subclavian artery arising
      from a calcified aneurysm of the Kommerell's diverticulum and bilateral carotid
      artery disease with atherosclerotic narrowing. Surgical relief was accomplished
      by excluding the aneurysm from circulation through the aortic arch and a 10 mm
      graft was interposed between the aberrant artery and the ascending aorta.

PMID- 18613970
TI  - Characterization of seed nuclei in glucagon aggregation using light scattering
      methods and field-flow fractionation.
AB  - BACKGROUND: Glucagon is a peptide hormone with many uses as a therapeutic agent,
      including the emergency treatment of hypoglycemia. Physical instability of
      glucagon in solution leads to problems with the manufacture, formulation, and
      delivery of this pharmaceutical product. Glucagon has been shown to aggregate and
      form fibrils and gels in vitro. Small oligomeric precursors serve to initiate and
      nucleate the aggregation process. In this study, these initial aggregates, or
      seed nuclei, are characterized in bulk solution using light scattering methods
      and field-flow fractionation. RESULTS: High molecular weight aggregates of
      glucagon were detected in otherwise monomeric solutions using light scattering
      techniques. These aggregates were detected upon initial mixing of glucagon powder
      in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon,
      the removal of aggregates by filtration significantly slowed the aggregation
      process. Field-flow fractionation was used to separate aggregates from monomeric
      glucagon and determine relative mass. The molar mass of the large aggregates was
      shown to grow appreciably over time as the glucagon solutions gelled. CONCLUSION:
      The results of this study indicate that initial glucagon solutions are
      predominantly monomeric, but contain small quantities of large aggregates. These
      results suggest that the initial aggregates are seed nuclei, or intermediates
      which catalyze the aggregation process, even at low concentrations.

PMID- 18613971
TI  - PM2.5 metal exposures and nocturnal heart rate variability: a panel study of
      boilermaker construction workers.
AB  - BACKGROUND: To better understand the mechanism(s) of particulate matter (PM)
      associated cardiovascular effects, research priorities include identifying the
      responsible PM characteristics. Evidence suggests that metals play a role in the
      cardiotoxicity of fine PM (PM2.5) and in exposure-related decreases in heart rate
      variability (HRV). We examined the association between daytime exposure to the
      metal content of PM2.5 and night HRV in a panel study of boilermaker construction
      workers exposed to metal-rich welding fumes. METHODS: Twenty-six male workers
      were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed
      to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of
      the mean squared differences of successive intervals) was summarized over the
      night (0:00-7:00). Workday, gravimetric PM2.5 samples were analyzed by x-ray
      fluorescence to determine metal content. We used linear mixed effects models to
      assess the associations between night rMSSD and PM2.5 metal exposures both with
      and without adjustment for total PM2.5. Matched ECG measurements from the non
      workday were used to control for individual cardiac risk factors and models were
      also adjusted for smoking status. To address collinearity between PM2.5 and metal
      content, we used a two-step approach that treated the residuals from linear
      regression models of each metal on PM2.5 as surrogates for the differential
      effects of metal exposures in models for night rMSSD. RESULTS: The median PM2.5
      exposure was 650 microg/m3; median metal exposures for iron, manganese, aluminum,
      copper, zinc, chromium, lead, and nickel ranged from 226 microg/m3 to non
      detectable. We found inverse linear associations in exposure-response models with
      increased metal exposures associated with decreased night rMSSD. A statistically
      significant association for manganese was observed, with a decline of 0.130 msec
      (95% CI: -0.162, -0.098) in night rMSSD for every 1 microg/m3 increase in
      manganese. However, even after adjusting for individual metals, increases in
      total PM2.5 exposures were associated with declines in night rMSSD. CONCLUSION:
      These results support the cardiotoxicity of PM2.5 metal exposures, specifically
      manganese. However the metal component alone did not account for the observed
      declines in night HRV. Therefore, results suggest the importance of other PM
      elemental components.

PMID- 18613972
TI  - At-TAX: a whole genome tiling array resource for developmental expression
      analysis and transcript identification in Arabidopsis thaliana.
AB  - Gene expression maps for model organisms, including Arabidopsis thaliana, have
      typically been created using gene-centric expression arrays. Here, we describe a
      comprehensive expression atlas, Arabidopsis thaliana Tiling Array Express (At
      TAX), which is based on whole-genome tiling arrays. We demonstrate that tiling
      arrays are accurate tools for gene expression analysis and identified more than
      1,000 unannotated transcribed regions. Visualizations of gene expression
      estimates, transcribed regions, and tiling probe measurements are accessible
      online at the At-TAX homepage.

PMID- 18613968
TI  - Correlation between pre-treatment quasispecies complexity and treatment outcome
      in chronic HCV genotype 3a.
AB  - Pre-treatment HCV quasispecies complexity and diversity may predict response to
      interferon based anti-viral therapy. The objective of this study was to
      retrospectively (1) examine temporal changes in quasispecies prior to the start
      of therapy and (2) investigate extensively quasispecies evolution in a group of
      10 chronically infected patients with genotype 3a, treated with pegylated alpha2a
      Interferon and ribavirin. The degree of sequence heterogeneity within the
      hypervariable region 1 was assessed by analyzing 20-30 individual clones in
      serial serum samples. Genetic parameters, including amino acid Shannon entropy,
      Hamming distance and genetic distance were calculated for each sample. Treatment
      outcome was divided into (1) sustained virological responders (SVR) and (2)
      treatment failure (TF). Our results indicate, (1) quasispecies complexity and
      diversity are lower in the SVR group, (2) quasispecies vary temporally and (3)
      genetic heterogeneity at baseline can be use to predict treatment outcome. We
      discuss the results from the perspective of replicative homeostasis.

PMID- 18613973
TI  - Altered gene expression changes in Arabidopsis leaf tissues and protoplasts in
      response to Plum pox virus infection.
AB  - BACKGROUND: Virus infection induces the activation and suppression of global gene
      expression in the host. Profiling gene expression changes in the host may provide
      insights into the molecular mechanisms that underlie host physiological and
      phenotypic responses to virus infection. In this study, the Arabidopsis
      Affymetrix ATH1 array was used to assess global gene expression changes in
      Arabidopsis thaliana plants infected with Plum pox virus (PPV). To identify early
      genes in response to PPV infection, an Arabidopsis synchronized single-cell
      transformation system was developed. Arabidopsis protoplasts were transfected
      with a PPV infectious clone and global gene expression changes in the transfected
      protoplasts were profiled. RESULTS: Microarray analysis of PPV-infected
      Arabidopsis leaf tissues identified 2013 and 1457 genes that were significantly
      (Q < or = 0.05) up- (> or = 2.5 fold) and downregulated (< or = -2.5 fold),
      respectively. Genes associated with soluble sugar, starch and amino acid,
      intracellular membrane/membrane-bound organelles, chloroplast, and protein fate
      were upregulated, while genes related to development/storage proteins, protein
      synthesis and translation, and cell wall-associated components were
      downregulated. These gene expression changes were associated with PPV infection
      and symptom development. Further transcriptional profiling of protoplasts
      transfected with a PPV infectious clone revealed the upregulation of defence and
      cellular signalling genes as early as 6 hours post transfection. A cross sequence
      comparison analysis of genes differentially regulated by PPV-infected Arabidopsis
      leaves against uniEST sequences derived from PPV-infected leaves of Prunus
      persica, a natural host of PPV, identified orthologs related to defence,
      metabolism and protein synthesis. The cross comparison of genes differentially
      regulated by PPV infection and by the infections of other positive sense RNA
      viruses revealed a common set of 416 genes. These identified genes, particularly
      the early responsive genes, may be critical in virus infection. CONCLUSION: Gene
      expression changes in PPV-infected Arabidopsis are the molecular basis of stress
      and defence-like responses, PPV pathogenesis and symptom development. The
      differentially regulated genes, particularly the early responsive genes, and a
      common set of genes regulated by infections of PPV and other positive sense RNA
      viruses identified in this study are candidates suitable for further functional
      characterization to shed lights on molecular virus-host interactions.

PMID- 18613975
TI  - Accumulation of GC donor splice signals in mammals.
AB  - The GT dinucleotide in the first two intron positions is the most conserved
      element of the U2 donor splice signals. However, in a small fraction of donor
      sites, GT is replaced by GC. A substantial enrichment of GC in donor sites of
      alternatively spliced genes has been observed previously in human, nematode and
      Arabidopsis, suggesting that GC signals are important for regulation of
      alternative splicing. We used parsimony analysis to reconstruct evolution of
      donor splice sites and inferred 298 GT > GC conversion events compared to 40 GC >
      GT conversion events in primate and rodent genomes. Thus, there was substantive
      accumulation of GC donor splice sites during the evolution of mammals.
      Accumulation of GC sites might have been driven by selection for alternative
      splicing. REVIEWERS: This article was reviewed by Jerzy Jurka and Anton
      Nekrutenko. For the full reviews, please go to the Reviewers' Reports section.

PMID- 18613976
TI  - The effect of a large proximal haemodialysis arterio-venous fistula on weaning
      off cardiopulmonary bypass: case report.
AB  - An increasing number of renal dialysis-dependent patients with Arterio-Venous
      fistulae are undergoing cardiac surgery.The fistula has important effects on
      systemic hemodynamics in dialysis patients. The flow is significantly and
      positively related to cardiac output and cardiac index, and inversely related to
      pulmonary vascular resistance.Few problems are encountered on cardiopulmonary
      bypass despite left to right shunting of blood. We present an unusual case in
      which a large brachial Arterio-Venous fistula with large collaterals prevented
      weaning off cardiopulmonary bypass.

PMID- 18613974
TI  - The last universal common ancestor: emergence, constitution and genetic legacy of
      an elusive forerunner.
AB  - BACKGROUND: Since the reclassification of all life forms in three Domains
      (Archaea, Bacteria, Eukarya), the identity of their alleged forerunner (Last
      Universal Common Ancestor or LUCA) has been the subject of extensive
      controversies: progenote or already complex organism, prokaryote or
      protoeukaryote, thermophile or mesophile, product of a protracted progression
      from simple replicators to complex cells or born in the cradle of "catalytically
      closed" entities? We present a critical survey of the topic and suggest a
      scenario. RESULTS: LUCA does not appear to have been a simple, primitive,
      hyperthermophilic prokaryote but rather a complex community of protoeukaryotes
      with a RNA genome, adapted to a broad range of moderate temperatures, genetically
      redundant, morphologically and metabolically diverse. LUCA's genetic redundancy
      predicts loss of paralogous gene copies in divergent lineages to be a significant
      source of phylogenetic anomalies, i.e. instances where a protein tree departs
      from the SSU-rRNA genealogy; consequently, horizontal gene transfer may not have
      the rampant character assumed by many. Examining membrane lipids suggest LUCA had
      sn1,2 ester fatty acid lipids from which Archaea emerged from the outset as
      thermophilic by "thermoreduction," with a new type of membrane, composed of sn2,3
      ether isoprenoid lipids; this occurred without major enzymatic reconversion.
      Bacteria emerged by reductive evolution from LUCA and some lineages further
      acquired extreme thermophily by convergent evolution. This scenario is compatible
      with the hypothesis that the RNA to DNA transition resulted from different viral
      invasions as proposed by Forterre. Beyond the controversy opposing "replication
      first" to metabolism first", the predictive arguments of theories on "catalytic
      closure" or "compositional heredity" heavily weigh in favour of LUCA's ancestors
      having emerged as complex, self-replicating entities from which a genetic code
      arose under natural selection. CONCLUSION: Life was born complex and the LUCA
      displayed that heritage. It had the "body "of a mesophilic eukaryote well before
      maturing by endosymbiosis into an organism adapted to an atmosphere rich in
      oxygen. Abundant indications suggest reductive evolution of this complex and
      heterogeneous entity towards the "prokaryotic" Domains Archaea and Bacteria. The
      word "prokaryote" should be abandoned because epistemologically unsound.
      REVIEWERS: This article was reviewed by Anthony Poole, Patrick Forterre, and
      Nicolas Galtier.

PMID- 18613977
TI  - Immunity related genes in dipterans share common enrichment of AT-rich motifs in
      their 5' regulatory regions that are potentially involved in nucleosome
      formation.
AB  - BACKGROUND: Understanding the transcriptional regulation mechanisms in response
      to environmental challenges is of fundamental importance in biology.
      Transcription factors associated to response elements and the chromatin structure
      had proven to play important roles in gene expression regulation. We have
      analyzed promoter regions of dipteran genes induced in response to immune
      challenge, in search for particular sequence patterns involved in their
      transcriptional regulation. RESULTS: 5' upstream regions of D. melanogaster and
      A. gambiae immunity-induced genes and their corresponding orthologous genes in 11
      non-melanogaster drosophilid species and Ae. aegypti share enrichment in AT-rich
      short motifs. AT-rich motifs are associated with nucleosome formation as
      predicted by two different algorithms. In A. gambiae and D. melanogaster, many
      immunity genes 5' upstream sequences also showed NFkappaB response elements,
      located within 500 bp from the transcription start site. In A. gambiae, the
      frequency of ATAA motif near the NFkappaB response elements was increased,
      suggesting a functional link between nucleosome formation/remodelling and
      NFkappaB regulation of transcription. CONCLUSION: AT-rich motif enrichment in 5'
      upstream sequences in A. gambiae, Ae. aegypti and the Drosophila genus immunity
      genes suggests a particular pattern of nucleosome formation/chromatin
      organization. The co-occurrence of such motifs with the NFkappaB response
      elements suggests that these sequence signatures may be functionally involved in
      transcriptional activation during dipteran immune response. AT-rich motif
      enrichment in regulatory regions in this group of co-regulated genes could
      represent an evolutionary constrained signature in dipterans and perhaps other
      distantly species.

PMID- 18613978
TI  - Modulation of microtubule assembly by the HIV-1 Tat protein is strongly dependent
      on zinc binding to Tat.
AB  - BACKGROUND: During HIV-1 infection, the Tat protein plays a key role by
      transactivating the transcription of the HIV-1 proviral DNA. In addition, Tat
      induces apoptosis of non-infected T lymphocytes, leading to a massive loss of
      immune competence. This apoptosis is notably mediated by the interaction of Tat
      with microtubules, which are dynamic components essential for cell structure and
      division. Tat binds two Zn2+ ions through its conserved cysteine-rich region in
      vitro, but the role of zinc in the structure and properties of Tat is still
      controversial. RESULTS: To investigate the role of zinc, we first characterized
      Tat apo- and holo-forms by fluorescence correlation spectroscopy and time
      resolved fluorescence spectroscopy. Both of the Tat forms are monomeric and
      poorly folded but differ by local conformational changes in the vicinity of the
      cysteine-rich region. The interaction of the two Tat forms with tubulin dimers
      and microtubules was monitored by analytical ultracentrifugation, turbidity
      measurements and electron microscopy. At 20 degrees C, both of the Tat forms bind
      tubulin dimers, but only the holo-Tat was found to form discrete complexes. At 37
      degrees C, both forms promoted the nucleation and increased the elongation rates
      of tubulin assembly. However, only the holo-Tat increased the amount of
      microtubules, decreased the tubulin critical concentration, and stabilized the
      microtubules. In contrast, apo-Tat induced a large amount of tubulin aggregates.
      CONCLUSION: Our data suggest that holo-Tat corresponds to the active form,
      responsible for the Tat-mediated apoptosis.

PMID- 18613980
TI  - Expression of CD56 isoforms in primary and relapsed adult granulosa cell tumors
      of the ovary.
AB  - BACKGROUND: Adult granulosa cell tumors of the ovary (GCTs) are sex cord stromal
      tumors of unpredictable behaviour. Up to now, the prediction of the
      relapsing/malignant potential remains difficult. CD56 (NCAM) in GCTs was
      previously described in only two studies. However, the expression of its isoforms
      was not examined. METHODS: 30 GCTs (16 primaries, 14 relapses) were investigated
      immunohistochemically with antibodies against Pan-CD56 (CD56Pan) and the isoform
      with 140/180 kDa length (CD56140/180 kDa). The reaction was assessed with respect
      to percentage of positive cells and intensity of staining. RESULTS: In all GCTs,
      CD56Pan was expressed, but differences were found between primaries and relapses.
      The percentage of CD56Pan positive tumor cells was lower in relapses, whereas
      CD56140/180 kDa showed a higher staining intensity in the latter. CONCLUSION:
      Expression of CD56 is an additional sensitive and helpful immunohistochemical
      tool for histopathologists diagnosing a GCT. It does not seem possible to provide
      a validly individual risk assessment. However, the different expression of CD56
      isoforms might indicate important changes in the course to a more malignant
      behaviour.

PMID- 18613979
TI  - A cryptic promoter in the first exon of the SPG4 gene directs the synthesis of
      the 60-kDa spastin isoform.
AB  - BACKGROUND: Mutations in SPG4 cause the most common form of autosomal dominant
      hereditary spastic paraplegia, a neurodegenerative disease characterized by
      weakness and spasticity of the lower limbs due to degeneration of the
      corticospinal tract. SPG4 encodes spastin, a microtubule-severing ATPase
      belonging to the AAA family. Two isoforms of spastin, 68 and 60 kDa,
      respectively, are variably abundant in tissues, show different subcellular
      localizations and interact with distinct molecules. The isoforms arise through
      alternative initiation of translation from two AUG codons in exon 1; however, it
      is unclear how regulation of their expression may be achieved. RESULTS: We
      present data that rule out the hypothesis that a cap-independent mechanism may be
      involved in the translation of the 60-kDa spastin isoform. Instead, we provide
      evidence for a complex transcriptional regulation of SPG4 that involves both a
      TATA-less ubiquitous promoter and a cryptic promoter in exon 1. The cryptic
      promoter covers the 5'-UTR and overlaps with the coding region of the gene. By
      using promoter-less constructs in various experimental settings, we found that
      the cryptic promoter is active in HeLa, HEK293 and motoneuronal NSC34 cells but
      not in SH-SY-5Y neuroblastoma cells. We showed that the cryptic promoter directs
      the synthesis of a SPG4 transcript that contains a shorter 5'-UTR and translates
      the 60-kDa spastin isoform selectively. Two polymorphisms (S44L and P45Q),
      leading to an early onset severe form of hereditary spastic paraplegia when
      present in heterozygosity with a mutant allele, fall a few nucleotides downstream
      of the novel transcriptional start site, opening up the possibility that they may
      exert their modifier effect at the transcriptional level. We provide evidence
      that at least one of them decreases the activity of the cryptic promoter in
      luciferase assays. CONCLUSION: We identified a cryptic promoter in exon 1 of the
      SPG4 gene that selectively drives the expression of the 60-kDa spastin isoform in
      a tissue-regulated manner. These data may have implications for the understanding
      of the biology of spastin and the pathogenic basis of hereditary spastic
      paraplegia.

PMID- 18613981
TI  - Skin permeation mechanism and bioavailability enhancement of celecoxib from
      transdermally applied nanoemulsion.
AB  - BACKGROUND: Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been
      recommended orally for the treatment of arthritis and osteoarthritis. Long term
      oral administration of celecoxib produces serious gastrointestinal side effects.
      It is a highly lipophilic, poorly soluble drug with oral bioavailability of
      around 40% (Capsule). Therefore the aim of the present investigation was to
      assess the skin permeation mechanism and bioavailability of celecoxib by
      transdermally applied nanoemulsion formulation. Optimized oil-in-water
      nanoemulsion of celecoxib was prepared by the aqueous phase titration method.
      Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR
      spectral analysis, DSC thermogram, activation energy measurement and
      histopathological examination. The optimized nanoemulsion was subjected to
      pharmacokinetic (bioavailability) studies on Wistar male rats. RESULTS: FTIR
      spectra and DSC thermogram of skin treated with nanoemulsion indicated that
      permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The
      significant decrease in activation energy (2.373 kcal/mol) for celecoxib
      permeation across rat skin indicated that the stratum corneum lipid bilayers were
      significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the
      disruption of lipid bilayers as distinct voids and empty spaces were visible in
      the epidermal region. The absorption of celecoxib through transdermally applied
      nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in
      bioavailability as compared to oral capsule formulation. CONCLUSION: Results of
      skin permeation mechanism and pharmacokinetic studies indicated that the
      nanoemulsions can be successfully used as potential vehicles for enhancement of
      skin permeation and bioavailability of poorly soluble drugs.

PMID- 18613982
TI  - Staged surgical treatment for severe and rigid scoliosis.
AB  - BACKGROUND: A retrospective study of staged surgery for severe rigid scoliosis.
      The purpose of this study was to evaluate the result of staged surgery in
      treatment of severe rigid scoliosis and to discuss the indications. METHODS: From
      1998 to 2006, 21 cases of severe rigid scoliosis with coronal Cobb angle more
      than 80 degrees were treated by staged surgeries including anterior release and
      halo-pelvic traction as first stage surgery and posterior instrumentation and
      spinal fusion as second stage. Pedicle subtraction osteotomy(PSO) was added in
      second stage according to spine rigidity. Among the 21 patients, 8 were male and
      13 female with an average age of 15.3 years (rang from 4 to 23 years). The mean
      pre-operative Cobb angle was 110.5 degrees (80 degrees -145 degrees ) with a mean
      spine flexibility of 13%. Radiological parameters at different operative time
      points were analyzed (mean time of follow-up: 51 months). RESULTS: External
      appearance of all patients improved significantly. The average correction rate
      was 65.2% (ranging from 39.8% to 79.5%) with mean correction loss of 2.23 degrees
      at the end of follow-up. No decompensation of trunk has been found. Mean distance
      between the midline of C7 and midsacral line was 1.19 cm +/- 0.51. Two patients
      had neurological complications: one patient had motor deficit and recovered
      incompletely. CONCLUSION: Staged operation and halo-pelvic traction offer a safe
      and effective way in treatment of severe rigid scoliosis. Patients whose Cobb
      angle was more than 80 degrees and the flexibility of the spine was less than 20%
      should be treated in this way, and those whose flexibility of the spine was less
      than 10% and the Cobb angle remained more than 70 degrees after 1st stage
      anterior release and halo-pelvic traction should undergo pedicle subtraction
      osteotomy (PSO) in the second surgery.

PMID- 18613983
TI  - Bioprotective properties of seaweeds: in vitro evaluation of antioxidant activity
      and antimicrobial activity against food borne bacteria in relation to
      polyphenolic content.
AB  - BACKGROUND: For many years chemical preservatives have been used in food, to act
      as either antimicrobials or antioxidants or both. In general, consumers regard
      additive-free foods as safer since preservatives can cause health hazards like
      asthma and cancer and are suspected to be mutagenic and neurotoxic. The present
      study was carried out to evaluate the antimicrobial and antioxidant activity of
      methanolic extracts of seaweeds, with a view to developing safer food
      preservatives. METHODS: Ten edible seaweeds, which have wide pharmaceutical
      application, were collected from Central Marine Fisheries Research Institute,
      Tamil Nadu, India and evaluated for antioxidant and antimicrobial activity
      against food borne pathogens. RESULTS: The results indicate that Gelidiella
      acerosa has the highest antioxidant activity while Haligra sps exhibited
      antibacterial activity against Staphylococcus aureus (MTCC 96). CONCLUSION:
      Quantitative analysis of the total phenolic content of the seaweeds indicated
      that Gelidella acerosa and Haligra sps have high phenolic contents, which
      correlated to their respective antioxidant and antimicrobial activity.

PMID- 18613984
TI  - Associations between neonatal birth dimensions and maternal essential and trans
      fatty acid contents during pregnancy and at delivery.
AB  - Since birth dimensions have prognostic potential for later development and
      health, possible associations between neonatal birth dimensions and selected
      maternal plasma fatty acid contents were investigated, using data from 782 mother
      infant pairs of the Maastricht Essential Fatty Acid Birth cohort. Unadjusted and
      multivariable-adjusted regression analyses were applied to study the associations
      between birth weight, birth length or head circumference and the relative
      contents of DHA, arachidonic acid (AA), dihomo-gamma-linolenic acid (DGLA) and 18
      : 1trans (18 : 1t) in maternal plasma phospholipids sampled during early, middle
      and late pregnancies, and at delivery. Where appropriate, corrections were made
      for relevant covariables. Significant 'positive' associations were observed
      between maternal DHA contents (especially early in pregnancy) and birth weight (B
      = 52.10 g, 95 % CI 20.40, 83.80) and head circumference (B = 0.223 cm, 95 % CI
      0.074, 0.372). AA contents at late pregnancy were 'negatively' associated with
      birth weight (B = - 44.25 g, 95 % CI - 68.33, - 20.16) and birth length (B = -
      0.200 cm, 95 % CI - 0.335, - 0.065). Significant 'negative' associations were
      also observed for AA contents at delivery and birth weight (B = - 27.08 g, 95 %
      CI - 47.11, - 7.056) and birth length (B = - 0.207 cm, 95 % CI - 0.330, - 0.084).
      Maternal DGLA contents at delivery were also significantly 'negatively'
      associated with neonatal birth weight (B = - 85.76 g, 95 % CI - 130.9, - 40.61)
      and birth length (B = - 0.413 cm, 95 % CI - 0.680, - 0.146). No significant
      associations were observed for maternal 18 : 1t contents. We conclude that during
      early pregnancy, maternal DHA content may programme fetal growth in a positive
      way. Maternal AA and DGLA in late pregnancy might be involved in fetal growth
      limitation.

PMID- 18613985
TI  - Peripartal feeding strategy with different n-6: n-3 ratios in sows: effects on
      sows' performance, inflammatory and periparturient metabolic parameters.
AB  - The present study aimed to investigate the effects of two lactation sow feeds,
      differing in n-6:n-3 ratio, given to sows before parturition on body condition
      and feed intake, periparturient metabolism (leptin, insulin, triiodothyronine
      (T3) and thyroxine (T4)), inflammatory parameters (TNFalpha, IL-6, serum amyloid
      A (SAA)) and on piglet performance (birth weight, survivability). The feed
      contained either a low (supplemented with fish oil; f groups) or high
      (supplemented with sunflower-seed oil; s groups) n-6:n-3 ratio and was
      administered from 8 d (f8, s8) or 3 d (f3, s3) before parturition until weaning.
      The level of inclusion of the oil sources was 2 %. Seventy-two sows were randomly
      allocated 8 d before expected farrowing into four groups: f3, f8, s3, s8. Type of
      feed had a significant influence on the sows' feed intake during the first 2 d of
      lactation (s < f), leptin on days 4, 3 and 2 before parturition (f < s), insulin
      on day 1 after parturition (f < s), T4 on the day before parturition (s < f) and
      rectal temperature on the day after parturition (f < s). Onset of administration
      of the feed (3 v. 8 d) had significant effects on leptin on day 2 before
      parturition (8 < 3), insulin on day 4 before parturition (3 < 8), T3 on day 4
      before parturition and on the day after parturition (3 < 8), SAA on day 3 after
      parturition (8 < 3) and piglet weight during the first days postpartum (3 < 8).
      In conclusion, under the present conditions, a lactation feed low in n-6:n-3
      ratio administered from 8 d before farrowing ensures improved feed intake during
      the first days postpartum and was associated with a better metabolic change and
      inflammatory profile in sows in the periparturient period.

PMID- 18613987
TI  - X-ray Diffraction: A Practical Approach.
AB  - X-ray Diffraction: A Practical Approach, C. Suryanarayana and M. Grant Norton,
      1998. Plenum Press, New York and London. xiii + 273 pages. (hardback, $49.50,
      U.S. and Canada; $59.40, elsewhere).It is the aim of this text to teach
      undergraduates majoring in materials science the use of powder X-ray diffraction
      for materials characterization. Since it does not treat X-ray diffraction and
      crystallography in a general way, it would have been better if it were given a
      more specific title, such as X-Ray Powder Diffraction for Metallurgical
      Characterization. A Primer and Workbook. As a laboratory course with work pages
      to be filled out by the student, it might have been spiral-bound to facilitate
      such use.

PMID- 18613986
TI  - Ovicidal activity of Paecilomyces lilacinus on Moniezia sp. eggs.
AB  - The ovicidal activity of Paecilomyces lilacinus was evaluated on Moniezia sp.
      eggs. Eggs of Moniezia sp. were incubated on plates with 2% agar-water inoculated
      with grown fungal isolates and a control treatment without fungus. After 5, 10
      and 15 days post-inoculation, the eggs were removed and classified according to
      the following parameters: effect type 1, lytic effect without morphological
      damage to eggshells; effect type 2, lytic effect with morphological change in
      embryos and eggshells; and effect type 3, lytic effect with morphological change
      in embryos and eggshells, with hyphal penetration and internal colonization of
      eggs. Paecilomyces lilacinus showed percentages for ovicidal activity (P < 0.01),
      mainly type 3 effect, of 19, 20 and 23% on eggs of Moniezia sp., after 5, 10 and
      15 days post-inoculation, respectively. Therefore P. lilacinus can be considered
      as a potential biological control agent for this cestode.

PMID- 18613988
TI  - 37-year-old man with painful foot.

PMID- 18613989
TI  - Elderly woman with orange urine and purple hands.

PMID- 18613990
TI  - Next generation of health information tools: where do we go from here?

PMID- 18613992
TI  - Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary
      prevention trial.
AB  - OBJECTIVE: To compare the lipid-lowering effects of an alternative regimen
      (lifestyle changes, red yeast rice, and fish oil) with a standard dose of a 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). PATIENTS AND
      METHODS: This randomized trial enrolled 74 patients with hypercholesterolemia who
      met Adult Treatment Panel III criteria for primary prevention using statin
      therapy. All participants were randomized to an alternative treatment group (AG)
      or to receive simvastatin (40 mg/d) in this open-label trial conducted between
      April 1, 2006, and June 30, 2006. The alternative treatment included therapeutic
      lifestyle changes, ingestion of red yeast rice, and fish oil supplements for 12
      weeks. The simvastatin group received medication and traditional counseling. The
      primary outcome measure was the percentage change in low-density lipoprotein
      cholesterol (LDL-C). Secondary measures were changes in other lipoproteins and
      weight loss. RESULTS: There was a statistically significant reduction in LDL-C
      levels in both the AG (-42.4%+/-15%) (P<.001) and the simvastatin group (-39.6%+/
      20%) (P<.001). No significant differences were noted between groups. The AG also
      demonstrated significant reductions in triglycerides (-29% vs -9.3%; 95%
      confidence interval, -61 to -11.7; P=.003) and weight (-5.5% vs -0.4%; 95%
      confidence interval, -5.5 to -3.4; P<.001) compared with the simvastatin group.
      CONCLUSION: Lifestyle changes combined with ingestion of red yeast rice and fish
      oil reduced LDL-C in proportions similar to standard therapy with simvastatin.
      Pending confirmation in larger trials, this multifactorial, alternative approach
      to lipid lowering has promise for a subset of patients unwilling or unable to
      take statins.

PMID- 18613991
TI  - Chronic care model and shared care in diabetes: randomized trial of an electronic
      decision support system.
AB  - OBJECTIVE: To assess the effect of a specialist telemedicine intervention for
      improving diabetes care using the chronic care model (CCM). PARTICIPANTS AND
      METHODS: As part of the CCM, 97 primary care physicians at 6 primary care
      practices in Rochester, MN, referred 639 patients to an on-site diabetes educator
      between July 1, 2001, and December 31, 2003. On first referral, physicians were
      centrally randomized to receive a telemedicine intervention (specialty advice and
      evidence-based messages regarding medication management for cardiovascular risk)
      or no intervention, keeping outcome assessors and data analysts blinded to group
      assignment. After each subsequent clinical encounter, endocrinologists reviewed
      an abstract from the patient's electronic medical record and provided management
      recommendations and supporting evidence to intervention physicians via e-mail.
      Control physicians received e-mail with periodic generic information about
      cardiovascular risk reduction in diabetes. Outcome measures included diabetes
      care processes (diabetes test completion), outcomes (metabolic and cardiovascular
      risk factors, estimated coronary artery disease risk), and patient costs (payer
      perspective). RESULTS: During the intervention, 951 (70%) of the 1361
      endocrinology reviews detected performance gaps and resulted in a message;
      primary care physicians reported using 49% of messages in patient care. With a
      mean of 21 months' follow-up, the intervention, compared with control, did not
      significantly enhance metabolic outcomes or reduce estimated risk of coronary
      artery disease (adjusted mean difference, -1%; 95% confidence interval, -19% to
      17%). The intervention group incurred lower costs (P=.02) but not in diabetes
      related costs. CONCLUSION: Specialty telemedicine did not significantly enhance
      the value of CCM in primary care.

PMID- 18613994
TI  - Predictive value of blood and bone marrow flow cytometry in B-cell lymphoma
      classification: comparative analysis of flow cytometry and tissue biopsy in 252
      patients.
AB  - OBJECTIVE: To study the effectiveness of peripheral blood (PB) and bone marrow
      flow cytometric immunophenotyping (FCIP) in predicting the histologic B-cell
      lymphoma type. PATIENTS AND METHODS: We studied the FCIP results and tissue
      histopathology from 252 patients with B-cell lymphoma seen at Mayo Clinic's site
      in Rochester, MN, between January 1, 1997, and January 1, 2004, who had positive
      results on PB, bone marrow, or body fluid FCIP and a corresponding diagnostic
      tissue biopsy specimen. RESULTS: Most of the B-cell lymphomas studied were low
      grade, with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma being
      most common. Flow cytometric immunophenotyping histogram analysis was more
      informative than tabulated percentage antigen positivity; surface immunoglobulin
      and CD20 staining intensity, CD5 and CD23 positivity, CD10 positivity, and the
      coexpression of CD11c/CD22 and CD103 were the most pertinent markers. Using these
      FCIP parameters and strict immunophenotypic definitions for CLL, mantle cell
      lymphoma (MCL), and hairy cell leukemia, we obtained greater than 95% specificity
      for each diagnosis. However, we encountered the following exceptions to standard
      paradigms of B-cell lymphoma-associated FCIP: (1) CD5 expression by disorders
      distinct from CLL and MCL, (2) lack of uniform CD5 positivity in some CLL and MCL
      cases, (3) absence of CD10 in approximately 50% of follicular lymphomas, and (4)
      expression of CD103 by occasional marginal zone lymphomas. CONCLUSION: Stringent
      interpretation of PB and bone marrow FCIP results enables identification of
      certain B-cell lymphoma types. However, the observed exceptions to accepted
      immunophenotypic paradigms highlight the occasional phenotypic overlap among
      diseases and emphasize that a systematic approach to FCIP interpretations is key
      to providing clinically useful diagnostic information.

PMID- 18613993
TI  - Spectrum of dizziness visits to US emergency departments: cross-sectional
      analysis from a nationally representative sample.
AB  - OBJECTIVE: To describe the spectrum of visits to US emergency departments (EDs)
      for acute dizziness and determine whether ED patients with dizziness are
      diagnosed as having a range of benign and dangerous medical disorders, rather
      than predominantly vestibular ones. PATIENTS AND METHODS: A cross-sectional study
      of ED visits from the National Hospital Ambulatory Medical Care Survey (NHAMCS)
      used a weighted sample of US ED visits (1993-2005) to measure patient and
      hospital demographics, ED diagnoses, and resource use in cases vs controls
      without dizziness. Dizziness in patients 16 years or older was defined as an
      NHAMCS reason-for-visit code of dizziness/vertigo (1225.0) or a final
      International Classification of Diseases, Ninth Revision, Clinical Modification
      diagnosis of dizziness/vertigo (780.4) or of a vestibular disorder (386.x).
      RESULTS: A total of 9472 dizziness cases (3.3% of visits) were sampled over 13
      years (weighted 33.6 million). Top diagnostic groups were otologic/vestibular
      (32.9%), cardiovascular (21.1%), respiratory (11.5%), neurologic (11.2%,
      including 4% cerebrovascular), metabolic (11.0%), injury/poisoning (10.6%),
      psychiatric (7.2%), digestive (7.0%), genitourinary (5.1%), and infectious
      (2.9%). Nearly half of the cases (49.2%) were given a medical diagnosis, and
      22.1% were given only a symptom diagnosis. Predefined dangerous disorders were
      diagnosed in 15%, especially among those older than 50 years (20.9% vs 9.3%;
      P<.001). Dizziness cases were evaluated longer (mean 4.0 vs 3.4 hours), imaged
      disproportionately (18.0% vs 6.9% undergoing computed tomography or magnetic
      resonance imaging), and admitted more often (18.8% vs 14.8%) (all P<.001).
      CONCLUSION: Dizziness is not attributed to a vestibular disorder in most ED cases
      and often is associated with cardiovascular or other medical causes, including
      dangerous ones. Resource use is substantial, yet many patients remain
      undiagnosed.

PMID- 18613995
TI  - Subspecialty differences in asthma characteristics and management.
AB  - OBJECTIVE: To determine the nature and extent to which asthma characteristics and
      management differ between allergy and pulmonary subspecialists. PATIENTS AND
      METHODS: We used baseline data from 3342 adults enrolled in The Epidemiology and
      Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study, a
      multicenter, observational cohort recruited from subspecialty practices across
      the United States. Information on physician subspecialty, asthma history,
      allergic status, lung function, medication use, and recent health care use was
      collected from January 1, 2001, through April 30, 2004, via study coordinator
      administered interviews and self-administered validated questionnaires. RESULTS:
      In the TENOR study, 2407 patients (72%) were treated by allergists and 935 (28%)
      by pulmonologists. Patients treated by pulmonologists were more likely to be
      black, be less educated, and have lower incomes than those treated by allergists.
      Pulmonary patients had more severe asthma as indicated by physician assessment,
      Global Initiative for Asthma classification, lung function, and number of asthma
      control problems. Regular use of a short-acting beta-agonist and systemic
      corticosteroid use were also higher among pulmonologist-treated patients than
      allergist-treated patients, consistent with greater asthma severity. Although
      evidence of allergic disease was prevalent in both types of patients, those
      treated by an allergist were more likely to receive skin testing or
      immunotherapy. In multivariate analyses adjusted for demographic differences,
      patients treated by pulmonologists were more likely to report health care use for
      asthma in the past 3 months. CONCLUSION: In general, asthma patients treated by
      pulmonologists have lower socioeconomic status, have more severe disease, require
      more medication, and report greater health care use than those treated by
      allergists.

PMID- 18613996
TI  - Placing COURAGE in context: review of the recent literature on managing stable
      coronary artery disease.
AB  - Coronary artery disease (CAD) is the leading cause of death in the United States,
      but prevention and intervention efforts are lowering mortality. This progress is
      being undercut by rising rates of obesity and diabetes, and adherence to evidence
      based prevention efforts is less than ideal. Many patients with CAD who are
      asymptomatic or have minimal symptoms undergo percutaneous coronary intervention
      (PCI) each year, even though PCI has not been demonstrated to improve survival
      for this group. Motivated by the recent controversy surrounding the Clinical
      Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE)
      trial, we reviewed randomized clinical trials with follow-up published in the
      past decade comparing medical management with revascularization for stable CAD to
      provide a context for the COURAGE trial. We searched for relevant studies
      published from January 1, 1997, until the date of electronic publication of the
      COURAGE study results, March 26, 2007; references cited in the COURAGE
      publication were also reviewed. Evidence shows that PCI does not decrease
      mortality or risk of myocardial infarction over optimal medical or lifestyle
      therapy in patients with chronic stable CAD. In published studies, early benefits
      in angina control afforded by revascularization wane over time; this could change
      with modern interventional therapies. The final word is not that medical therapy
      is superior for all patients, but that optimizing medical and lifestyle therapy
      is appropriate as an initial management strategy for most patients who do not
      have unstable or disabling symptoms. It is essential that systems are set in
      place to make the medical management of patients with CAD second nature; this
      focus could be one of the most powerful results of the COURAGE trial.

PMID- 18613997
TI  - Importance of low-grade albuminuria.
AB  - The well-described association between chronic kidney disease and cardiovascular
      disease is typically thought to originate from loss of renal function, as
      estimated by the glomerular filtration rate. However, recent data suggest that
      urinary albumin excretion has an important role in this association. Albuminuria
      is a marker of underlying vascular dysfunction and has been correlated with
      structural and functional integrity of the vasculature. Although the traditional
      upper limit of normal daily albumin excretion has been 30 mg/d, recent
      epidemiologic data suggest that levels in the general population are actually
      much lower. Further, within this range of low-grade albuminuria (LGA), increasing
      excretion rates are associated with increasing risk of cardiovascular disease.
      This association is independent of renal function, and in the earliest stages of
      chronic kidney disease, LGA seems to be a more important determinant than the
      glomerular filtration rate. This emerging association underscores the complexity
      of albumin excretion, in which subtle changes in albumin excretion reflect
      widespread vascular processes. Using the key words albuminuria, low-grade
      albuminuria, and microalbuminuria in a PubMed search of literature from January
      1, 1995, to February 29, 2008, this review summarizes the most recent data on LGA
      and its association with cardiovascular and renal disease.

PMID- 18613998
TI  - The ABCs of asthma control.
AB  - The new asthma guidelines have introduced impairment and risk assessments into
      the management of asthma. Impairment assessment is based on symptom frequency and
      pulmonary function, whereas risk assessment is based on exacerbation frequency
      and severity. These 2 measures determine the initial severity of asthma in the
      untreated patient as well as the degree of control in asthma once treatment has
      been initiated. The focus on asthma control is important because the attainment
      of control correlates with a better quality of life and reduction in health care
      use. We describe 4 easy steps to achieving asthma control in the ambulatory
      practice setting: (1) a standardized assessment of asthma symptoms using a 5
      question assessment tool called the Asthma Control Test, (2) a simple mnemonic
      that provides a systematic review of the comorbidities and clinical variables
      that contribute to uncontrolled asthma, (3) directed patient education, and (4) a
      schedule for ongoing care. Most if not all patients can achieve good control of
      their asthma with optimal care through an active partnership with their health
      care professionals.

PMID- 18614000
TI  - "Practical guide" to urine drug screening clarified.

PMID- 18614001
TI  - Oral contraceptives and breast cancer.

PMID- 18614003
TI  - Interchromosomal huddle kickstarts antiviral defense.
AB  - Long-distance chromosomal interactions are emerging as a potential mechanism of
      gene expression control. In this issue, Apostolou and Thanos (2008) describe how
      viral infection elicits interchromosomal associations between the interferon-beta
      (IFN-beta) gene enhancer and DNA binding sites of the transcription factor NF
      kappaB, resulting in the initiation of transcription and an antiviral response.

PMID- 18614002
TI  - Seeking a new biology through text mining.
AB  - Tens of thousands of biomedical journals exist, and the deluge of new articles in
      the biomedical sciences is leading to information overload. Hence, there is much
      interest in text mining, the use of computational tools to enhance the human
      ability to parse and understand complex text.

PMID- 18613999
TI  - Malignant melanoma in the 21st century: the emerging molecular landscape.
AB  - Malignant melanoma presents a substantial clinical challenge. Current diagnostic
      methods are limited in their ability to diagnose early disease and accurately
      predict individual risk of disease progression and outcome. The lack of adequate
      approaches to properly define disease subgroups precludes rational treatment
      design and selection. Better tools are urgently needed to provide more accurate
      and personalized melanoma patient management. Recent progress in the
      understanding of the molecular aberrations that underlie melanoma oncogenesis
      will likely advance the diagnosis, prognosis, and treatment of melanoma. The
      emerging pattern of molecular complexity in melanoma tumors mirrors the clinical
      diversity of the disease and highlights the notion that melanoma, like other
      cancers, is not a single disease but a heterogeneous group of disorders that
      arise from complex molecular changes. Understanding of molecular aberrations
      involving important cellular processes, such as cellular signaling networks, cell
      cycle regulation, and cell death, will be essential for better diagnosis,
      accurate assessment of prognosis, and rational design of effective therapeutics.
      Defining an individual patient's unique tumor characteristics may lead to
      personalized prediction of outcomes and selection of therapy. We review the
      emerging molecular landscape of melanoma and its implications for better
      management of patients with melanoma.

PMID- 18614004
TI  - Clearing the way for unpaused polymerases.
AB  - Heat shock loci in the polytene chromosomes of the fruit fly Drosophila undergo a
      characteristic change in appearance that coincides with the onset of gene
      expression. Petesch and Lis (2008) now show that nucleosomes are lost across the
      entire Hsp70 locus in an initial wave that precedes transcription by RNA
      polymerase II.

PMID- 18614005
TI  - Rab5 and rac team up in cell motility.
AB  - Cell motility requires actin assembly mediated by Rac, a Rho family GTPase. In
      this issue, Palamidessi et al. (2008) show that Rab5-directed trafficking of Rac
      to the cell membrane is required for Rac-mediated actin assembly. Trafficking of
      Rac may influence the mode of cell migration during morphogenesis and cancer
      metastasis.

PMID- 18614006
TI  - Deconstructing export of malaria proteins.
AB  - The virulence of the malaria parasite Plasmodium falciparum is mediated by
      parasite proteins exported to the surface of infected erythrocytes. In this
      issue, Maier et al. (2008) report a screen of malaria parasite genes predicted to
      be involved in parasite protein export and trafficking within the host
      erythrocyte and discover that many more than expected are essential for parasite
      survival in vitro.

PMID- 18614007
TI  - The mitochondrial proteome: from inventory to function.
AB  - Mitochondria are central to cellular energetics, metabolism, and signaling. In
      this issue, Pagliarini et al. (2008) report the largest compendium of mammalian
      mitochondrial proteins to date. Together with proteomic studies in yeast, this
      study represents an important step toward the systematic characterization of the
      mitochondrial proteome and of mitochondrial diseases.

PMID- 18614008
TI  - Evo-devo and an expanding evolutionary synthesis: a genetic theory of
      morphological evolution.
AB  - Biologists have long sought to understand which genes and what kinds of changes
      in their sequences are responsible for the evolution of morphological diversity.
      Here, I outline eight principles derived from molecular and evolutionary
      developmental biology and review recent studies of species divergence that have
      led to a genetic theory of morphological evolution, which states that (1) form
      evolves largely by altering the expression of functionally conserved proteins,
      and (2) such changes largely occur through mutations in the cis-regulatory
      sequences of pleiotropic developmental regulatory loci and of the target genes
      within the vast networks they control.

PMID- 18614009
TI  - Highly efficient, functional engraftment of skeletal muscle stem cells in
      dystrophic muscles.
AB  - Satellite cells reside beneath the basal lamina of skeletal muscle fibers and
      include cells that act as precursors for muscle growth and repair. Although they
      share a common anatomical localization and typically are considered a homogeneous
      population, satellite cells actually exhibit substantial heterogeneity. We used
      cell-surface marker expression to purify from the satellite cell pool a distinct
      population of skeletal muscle precursors (SMPs) that function as muscle stem
      cells. When engrafted into muscle of dystrophin-deficient mdx mice, purified SMPs
      contributed to up to 94% of myofibers, restoring dystrophin expression and
      significantly improving muscle histology and contractile function. Transplanted
      SMPs also entered the satellite cell compartment, renewing the endogenous stem
      cell pool and participating in subsequent rounds of injury repair. Together,
      these studies indicate the presence in adult skeletal muscle of prospectively
      isolatable muscle-forming stem cells and directly demonstrate the efficacy of
      myogenic stem cell transplant for treating muscle degenerative disease.

PMID- 18614010
TI  - Exported proteins required for virulence and rigidity of Plasmodium falciparum
      infected human erythrocytes.
AB  - A major part of virulence for Plasmodium falciparum malaria infection, the most
      lethal parasitic disease of humans, results from increased rigidity and
      adhesiveness of infected host red cells. These changes are caused by parasite
      proteins exported to the erythrocyte using novel trafficking machinery assembled
      in the host cell. To understand these unique modifications, we used a large-scale
      gene knockout strategy combined with functional screens to identify proteins
      exported into parasite-infected erythrocytes and involved in remodeling these
      cells. Eight genes were identified encoding proteins required for export of the
      parasite adhesin PfEMP1 and assembly of knobs that function as physical platforms
      to anchor the adhesin. Additionally, we show that multiple proteins play a role
      in generating increased rigidity of infected erythrocytes. Collectively these
      proteins function as a pathogen secretion system, similar to bacteria and may
      provide targets for antivirulence based therapies to a disease responsible for
      millions of deaths annually.

PMID- 18614011
TI  - Growth-inhibitory and tumor- suppressive functions of p53 depend on its
      repression of CD44 expression.
AB  - The p53 tumor suppressor is a key mediator of cellular responses to various
      stresses. Here, we show that under conditions of basal physiologic and cell
      culture stress, p53 inhibits expression of the CD44 cell-surface molecule via
      binding to a noncanonical p53-binding sequence in the CD44 promoter. This
      interaction enables an untransformed cell to respond to stress-induced, p53
      dependent cytostatic and apoptotic signals that would otherwise be blocked by the
      actions of CD44. In the absence of p53 function, the resulting derepressed CD44
      expression is essential for the growth and tumor-initiating ability of highly
      tumorigenic mammary epithelial cells. In both tumorigenic and nontumorigenic
      cells, CD44's expression is positively regulated by p63, a paralogue of p53. Our
      data indicate that CD44 is a key tumor-promoting agent in transformed tumor cells
      lacking p53 function. They also suggest that the derepression of CD44 resulting
      from inactivation of p53 can potentially aid the survival of immortalized,
      premalignant cells.

PMID- 18614012
TI  - Rapid, transcription-independent loss of nucleosomes over a large chromatin
      domain at Hsp70 loci.
AB  - To efficiently transcribe genes, RNA Polymerase II (Pol II) must overcome
      barriers imposed by nucleosomes and higher-order chromatin structure. Many genes,
      including Drosophila melanogaster Hsp70, undergo changes in chromatin structure
      upon activation. To characterize these changes, we mapped the nucleosome
      landscape of Hsp70 after an instantaneous heat shock at high spatial and temporal
      resolution. Surprisingly, we find an initial disruption of nucleosomes across the
      entire gene within 30 s after activation, faster than the rate of Pol II
      transcription, followed by a second further disruption within 2 min. This initial
      change occurs independently of Pol II transcription. Furthermore, the rapid loss
      of nucleosomes extends beyond Hsp70 and halts at the scs and scs' insulating
      elements. An RNAi screen of 28 transcription and chromatin-related factors
      reveals that depletion of heat shock factor, GAGA Factor, or Poly(ADP)-Ribose
      Polymerase or its activity abolishes the loss of nucleosomes upon Hsp70
      activation.

PMID- 18614013
TI  - Virus Infection Induces NF-kappaB-dependent interchromosomal associations
      mediating monoallelic IFN-beta gene expression.
AB  - Transcriptional activation of the IFN-beta gene by virus infection requires the
      cooperative assembly of an enhanceosome. We report that the stochastic and
      monoallelic expression of the IFN-beta gene depends on interchromosomal
      associations with three identified distinct genetic loci that could mediate
      binding of the limiting transcription factor NF-kappaB to the IFN-beta enhancer,
      thus triggering enhanceosome assembly and activation of transcription from this
      allele. The probability of a cell to express IFN-beta is dramatically increased
      when the cell is transfected with any of these loci. The secreted IFN-beta
      protein induces high-level expression of the enhanceosome factor IRF-7, which in
      turn promotes enhanceosome assembly and IFN-beta transcription from the remaining
      alleles and in other initially nonexpressing cells. Thus, the IFN-beta enhancer
      functions in a nonlinear fashion by working as a signal amplifier.

PMID- 18614014
TI  - LXR signaling couples sterol metabolism to proliferation in the acquired immune
      response.
AB  - Cholesterol is essential for membrane synthesis; however, the mechanisms that
      link cellular lipid metabolism to proliferation are incompletely understood. We
      demonstrate here that cellular cholesterol levels in dividing T cells are
      maintained in part through reciprocal regulation of the LXR and SREBP
      transcriptional programs. T cell activation triggers induction of the oxysterol
      metabolizing enzyme SULT2B1, consequent suppression of the LXR pathway for
      cholesterol transport, and promotion of the SREBP pathway for cholesterol
      synthesis. Ligation of LXR during T cell activation inhibits mitogen-driven
      expansion, whereas loss of LXRbeta confers a proliferative advantage.
      Inactivation of the sterol transporter ABCG1 uncouples LXR signaling from
      proliferation, directly linking sterol homeostasis to the antiproliferative
      action of LXR. Mice lacking LXRbeta exhibit lymphoid hyperplasia and enhanced
      responses to antigenic challenge, indicating that proper regulation of LXR
      dependent sterol metabolism is important for immune responses. These results
      implicate LXR signaling in a metabolic checkpoint that modulates cell
      proliferation and immunity.

PMID- 18614015
TI  - A mitochondrial protein compendium elucidates complex I disease biology.
AB  - Mitochondria are complex organelles whose dysfunction underlies a broad spectrum
      of human diseases. Identifying all of the proteins resident in this organelle and
      understanding how they integrate into pathways represent major challenges in cell
      biology. Toward this goal, we performed mass spectrometry, GFP tagging, and
      machine learning to create a mitochondrial compendium of 1098 genes and their
      protein expression across 14 mouse tissues. We link poorly characterized proteins
      in this inventory to known mitochondrial pathways by virtue of shared
      evolutionary history. Using this approach, we predict 19 proteins to be important
      for the function of complex I (CI) of the electron transport chain. We validate a
      subset of these predictions using RNAi, including C8orf38, which we further show
      harbors an inherited mutation in a lethal, infantile CI deficiency. Our results
      have important implications for understanding CI function and pathogenesis and,
      more generally, illustrate how our compendium can serve as a foundation for
      systematic investigations of mitochondria.

PMID- 18614016
TI  - Structural basis for the recognition of c-Src by its inactivator Csk.
AB  - The catalytic activity of the Src family of tyrosine kinases is suppressed by
      phosphorylation on a tyrosine residue located near the C terminus (Tyr 527 in c
      Src), which is catalyzed by C-terminal Src Kinase (Csk). Given the promiscuity of
      most tyrosine kinases, it is remarkable that the C-terminal tails of the Src
      family kinases are the only known targets of Csk. We have determined the crystal
      structure of a complex between the kinase domains of Csk and c-Src at 2.9 A
      resolution, revealing that interactions between these kinases position the C
      terminal tail of c-Src at the edge of the active site of Csk. Csk cannot
      phosphorylate substrates that lack this docking mechanism because the
      conventional substrate binding site used by most tyrosine kinases to recognize
      substrates is destabilized in Csk by a deletion in the activation loop.

PMID- 18614017
TI  - Endocytic trafficking of Rac is required for the spatial restriction of signaling
      in cell migration.
AB  - The small GTPases, Rab5 and Rac, are essential for endocytosis and actin
      remodeling, respectively. Coordination of these processes is critical to achieve
      spatial restriction of intracellular signaling, which is essential for a variety
      of polarized functions. Here, we show that clathrin- and Rab5-mediated
      endocytosis are required for the activation of Rac induced by motogenic stimuli.
      Rac activation occurs on early endosomes, where the RacGEF Tiam1 is also
      recruited. Subsequent recycling of Rac to the plasma membrane ensures localized
      signaling, leading to the formation of actin-based migratory protrusions. Thus,
      membrane trafficking of Rac is required for the spatial resolution of Rac
      dependent motogenic signals. We further demonstrate that a Rab5-to-Rac circuitry
      controls the morphology of motile mammalian tumor cells and primordial germinal
      cells during zebrafish development, suggesting that this circuitry is relevant
      for the regulation of migratory programs in various cells, in both in vitro
      settings and whole organisms.

PMID- 18614018
TI  - WHAMM is an Arp2/3 complex activator that binds microtubules and functions in ER
      to Golgi transport.
AB  - The Arp2/3 complex is an actin nucleator that plays a critical role in many
      cellular processes. Its activities are regulated by nucleation-promoting factors
      (NPFs) that function primarily during plasma membrane dynamics. Here we identify
      a mammalian NPF called WHAMM (WASP homolog associated with actin, membranes, and
      microtubules) that localizes to the cis-Golgi apparatus and tubulo-vesicular
      membrane transport intermediates. The modular organization of WHAMM includes an N
      terminal domain that mediates Golgi membrane association, a coiled-coil region
      that binds microtubules, and a WCA segment that stimulates Arp2/3-mediated actin
      polymerization. Overexpression and depletion studies indicate that WHAMM is
      important for maintaining Golgi structure and facilitating anterograde membrane
      transport. The ability of WHAMM to interact with microtubules plays a role in
      membrane tubulation, while its capacity to induce actin assembly promotes tubule
      elongation. Thus, WHAMM is an important regulator of membrane dynamics
      functioning at the interface of the microtubule and actin cytoskeletons.

PMID- 18614019
TI  - An RNAi screen of chromatin proteins identifies Tip60-p400 as a regulator of
      embryonic stem cell identity.
AB  - Proper regulation of chromatin structure is necessary for the maintenance of cell
      type-specific gene expression patterns. The embryonic stem cell (ESC) expression
      pattern governs self-renewal and pluripotency. Here, we present an RNAi screen in
      mouse ESCs of 1008 loci encoding chromatin proteins. We identified 68 proteins
      that exhibit diverse phenotypes upon knockdown (KD), including seven subunits of
      the Tip60-p400 complex. Phenotypic analyses revealed that Tip60-p400 is necessary
      to maintain characteristic features of ESCs. We show that p400 localization to
      the promoters of both silent and active genes is dependent upon histone H3 lysine
      4 trimethylation (H3K4me3). Furthermore, the Tip60-p400 KD gene expression
      profile is enriched for developmental regulators and significantly overlaps with
      that of the transcription factor Nanog. Depletion of Nanog reduces p400 binding
      to target promoters without affecting H3K4me3 levels. Together, these data
      indicate that Tip60-p400 integrates signals from Nanog and H3K4me3 to regulate
      gene expression in ESCs.

PMID- 18614021
TI  - SnapShot: var gene expression in the malaria parasite.

PMID- 18614020
TI  - Distinct role of long 3' UTR BDNF mRNA in spine morphology and synaptic
      plasticity in hippocampal neurons.
AB  - The brain produces two brain-derived neurotrophic factor (BDNF) transcripts, with
      either short or long 3' untranslated regions (3' UTRs). The physiological
      significance of the two forms of mRNAs encoding the same protein is unknown.
      Here, we show that the short and long 3' UTR BDNF mRNAs are involved in different
      cellular functions. The short 3' UTR mRNAs are restricted to somata, whereas the
      long 3' UTR mRNAs are also localized in dendrites. In a mouse mutant where the
      long 3' UTR is truncated, dendritic targeting of BDNF mRNAs is impaired. There is
      little BDNF in hippocampal dendrites despite normal levels of total BDNF protein.
      This mutant exhibits deficits in pruning and enlargement of dendritic spines, as
      well as selective impairment in long-term potentiation in dendrites, but not
      somata, of hippocampal neurons. These results provide insights into local and
      dendritic actions of BDNF and reveal a mechanism for differential regulation of
      subcellular functions of proteins.

PMID- 18614022
TI  - The ups and downs of translation-dependent plasticity.
AB  - Neuroscientists have been looking for good examples linking neuronal activity to
      gene expression/regulation involved in synaptic plasticity and the formation of
      long-term memories. New findings from Park et al. and Waung et al. in this issue
      of Neuron show that fast dendritic translation of the immediate-early gene
      Arc/Arg3.1 is involved in hippocampal mGluR-LTD, a protein synthesis-dependent
      form of plasticity.

PMID- 18614023
TI  - Retrograde tuning of tuning.
AB  - One way to localize sounds is to measure differences in sound intensity at the
      two ears. This comparison is made in the lateral superior olive, where signals
      from both ears converge. Magnusson et al. in this issue of Neuron show that
      dendritic GABA release can regulate this comparison, which may allow animals
      localizing sounds to adapt to listening conditions.

PMID- 18614024
TI  - Noncholinergic neurons in the basal forebrain: often neglected but motivationally
      salient.
AB  - Although noncholinergic neurons in the basal forebrain are known to contribute to
      cognition, their response properties in behaving animals is unclear. In this
      issue of Neuron, Lin and Nicolelis demonstrate that these neurons represent the
      motivational salience of sensory stimuli and may modulate cortical processing to
      direct top-down attention.

PMID- 18614025
TI  - Cerebral and peripheral amyloid phagocytes--an old liaison with a new twist.
AB  - In this month's issue of Nature Medicine, Town et al. suggest that peripheral
      macrophages invading the brain reduce cerebral amyloidosis and thus may play a
      key role in the pathogenesis of Alzheimer's disease (AD). This observation
      intensifies the longstanding controversy of whether mononuclear cells such as
      macrophages and/or microglial cells are beneficial or detrimental in AD.

PMID- 18614027
TI  - Vibrissal kinematics in 3D: tight coupling of azimuth, elevation, and torsion
      across different whisking modes.
AB  - Perception is usually an active process by which action selects and affects
      sensory information. During rodent active touch, whisker kinematics influences
      how objects activate sensory receptors. In order to fully characterize whisker
      motion, we reconstructed whisker position in 3D and decomposed whisker motion to
      all its degrees of freedom. We found that, across behavioral modes, in both head
      fixed and freely moving rats, whisker motion is characterized by translational
      movements and three rotary components: azimuth, elevation, and torsion. Whisker
      torsion, which has not previously been described, was large (up to 100 degrees),
      and torsional angles were highly correlated with whisker azimuths. The coupling
      of azimuth and torsion was consistent across whisking epochs and rats and was
      similar along rows but systematically varied across rows such that rows A and E
      counterrotated. Torsional rotation of the whiskers enables contact information to
      be mapped onto the circumference of the whisker follicles in a predictable manner
      across protraction-retraction cycles.

PMID- 18614028
TI  - Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy
      quinoline analogs is associated with decreased interstitial Abeta.
AB  - As a disease-modifying approach for Alzheimer's disease (AD), clioquinol (CQ)
      targets beta-amyloid (Abeta) reactions with synaptic Zn and Cu yet promotes metal
      uptake. Here we characterize the second-generation 8-hydroxy quinoline analog
      PBT2, which also targets metal-induced aggregation of Abeta, but is more
      effective as a Zn/Cu ionophore and has greater blood-brain barrier permeability.
      Given orally to two types of amyloid-bearing transgenic mouse models of AD, PBT2
      outperformed CQ by markedly decreasing soluble interstitial brain Abeta within
      hours and improving cognitive performance to exceed that of normal littermate
      controls within days. Nontransgenic mice were unaffected by PBT2. The current
      data demonstrate that ionophore activity, inhibition of in vitro metal-mediated
      Abeta reactions, and blood-brain barrier permeability are indices that predict a
      potential disease-modifying drug for AD. The speed of recovery of the animals
      underscores the acutely reversible nature of the cognitive deficits associated
      with transgenic models of AD.

PMID- 18614026
TI  - A role for brain stress systems in addiction.
AB  - Drug addiction is a chronically relapsing disorder characterized by compulsion to
      seek and take drugs and has been linked to dysregulation of brain regions that
      mediate reward and stress. Activation of brain stress systems is hypothesized to
      be key to the negative emotional state produced by dependence that drives drug
      seeking through negative reinforcement mechanisms. This review explores the role
      of brain stress systems (corticotropin-releasing factor, norepinephrine, orexin
      [hypocretin], vasopressin, dynorphin) and brain antistress systems (neuropeptide
      Y, nociceptin [orphanin FQ]) in drug dependence, with emphasis on the
      neuropharmacological function of extrahypothalamic systems in the extended
      amygdala. The brain stress and antistress systems may play a key role in the
      transition to and maintenance of drug dependence once initiated. Understanding
      the role of brain stress and antistress systems in addiction provides novel
      targets for treatment and prevention of addiction and insights into the
      organization and function of basic brain emotional circuitry.

PMID- 18614029
TI  - EphB receptors couple dendritic filopodia motility to synapse formation.
AB  - Motile dendritic filopodial processes are thought to be precursors of spine
      synapses, but how motility relates to cell-surface cues required for axon
      dendrite recognition and synaptogenesis remains unclear. We demonstrate with
      dynamic imaging that loss of EphBs results in reduced motility of filopodia in
      cultured cortical neurons and brain slice. EphB knockdown and rescue experiments
      during different developmental time windows show that EphBs are required for
      synaptogenesis only when filopodia are most abundant and motile. In the context
      of EphB knockdown and reduced filopodia motility, independent rescue of either
      motility with PAK or of Eph-ephrin binding with an EphB2 kinase mutant is not
      sufficient to restore synapse formation. Strikingly, the combination of PAK and
      kinase-inactive EphB2 rescues synaptogenesis. Deletion of the ephrin-binding
      domain from EphB2 precludes rescue, indicating that both motility and trans
      cellular interactions are required. Our findings provide a mechanistic link
      between dendritic filopodia motility and synapse differentiation.

PMID- 18614030
TI  - Elongation factor 2 and fragile X mental retardation protein control the dynamic
      translation of Arc/Arg3.1 essential for mGluR-LTD.
AB  - Group I metabotropic glutamate receptors (mGluR) induce long-term depression
      (LTD) that requires protein synthesis. Here, we demonstrate that Arc/Arg3.1 is
      translationally induced within 5 min of mGluR activation, and this response is
      essential for mGluR-dependent LTD. The increase in Arc/Arg3.1 translation
      requires eEF2K, a Ca(2+)/calmodulin-dependent kinase that binds mGluR and
      dissociates upon mGluR activation, whereupon it phosphorylates eEF2. Phospho-eEF2
      acts to slow the elongation step of translation and inhibits general protein
      synthesis but simultaneously increases Arc/Arg3.1 translation. Genetic deletion
      of eEF2K results in a selective deficit of rapid mGluR-dependent Arc/Arg3.1
      translation and mGluR-LTD. This rapid translational mechanism is disrupted in the
      fragile X disease mouse (Fmr1 KO) in which mGluR-LTD does not require de novo
      protein synthesis but does require Arc/Arg3.1. We propose a model in which eEF2K
      eEF2 and FMRP coordinately control the dynamic translation of Arc/Arg3.1 mRNA in
      dendrites that is critical for synapse-specific LTD.

PMID- 18614031
TI  - Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through
      persistent increases in AMPAR endocytosis rate.
AB  - Salient stimuli that modify behavior induce transcription of activity-regulated
      cytoskeleton-associated protein (Arc/Arg3.1) and transport Arc mRNA into
      dendrites, suggesting that local Arc translation mediates synaptic plasticity
      that encodes such stimuli. Here, we demonstrate that long-term synaptic
      depression (LTD) in hippocampal neurons induced by group 1 metabotropic glutamate
      receptors (mGluRs) relies on rapid translation of Arc. mGluR-LTD induction causes
      long-term increases in AMPA receptor endocytosis rate and dendritic synthesis of
      Arc, a component of the AMPAR endocytosis machinery. Knockdown of Arc prevents
      mGluRs from triggering AMPAR endocytosis or LTD, and acute blockade of new Arc
      synthesis with antisense oligonucleotides blocks mGluR-LTD and AMPAR trafficking.
      In contrast, LTD induced by NMDA receptors does not persistently alter AMPAR
      endocytosis rate, induce Arc synthesis, or require Arc protein. These data
      demonstrate a role for local Arc synthesis specifically in mGluR-LTD and suggest
      that mGluR-LTD may be one consequence of Arc mRNA induction during experience.

PMID- 18614032
TI  - Extent of voltage sensor movement during gating of shaker K+ channels.
AB  - Voltage-driven activation of Kv channels results from conformational changes of
      four voltage sensor domains (VSDs) that surround the K(+) selective pore domain.
      How the VSD helices rearrange during gating is an area of active research.
      Luminescence resonance energy transfer (LRET) is a powerful spectroscopic ruler
      uniquely suitable for addressing the conformational trajectory of these helices.
      Using a geometric analysis of numerous LRET measurements, we were able to
      estimate LRET probe positions relative to existing structural models. The
      experimental movement of helix S4 does not support a large 15-20 A transmembrane
      "paddle-type" movement or a near-zero A vertical "transporter-type" model.
      Rather, our measurements demonstrate a moderate S4 displacement of 10 +/- 5 A,
      with a vertical component of 5 +/- 2 A. The S3 segment moves 2 +/- 1 A in the
      opposite direction and is therefore not moving as an S3-S4 rigid body.

PMID- 18614033
TI  - Translation of sensory input into behavioral output via an olfactory system.
AB  - We investigate the logic by which sensory input is translated into behavioral
      output. First we provide a functional analysis of the entire odor receptor
      repertoire of an olfactory system. We construct tuning curves for the 21
      functional odor receptors of the Drosophila larva and show that they sharpen at
      lower odor doses. We construct a 21-dimensional odor space from the responses of
      the receptors and find that the distance between two odors correlates with the
      extent to which one odor masks the other. Mutational analysis shows that
      different receptors mediate the responses to different concentrations of an
      odorant. The summed response of the entire receptor repertoire correlates with
      the strength of the behavioral response. The activity of a small number of
      receptors is a surprisingly powerful predictor of behavior. Odors that inhibit
      more receptors are more likely to be repellents. Odor space is largely conserved
      between two dissimilar olfactory systems.

PMID- 18614034
TI  - Retrograde GABA signaling adjusts sound localization by balancing excitation and
      inhibition in the brainstem.
AB  - Central processing of acoustic cues is critically dependent on the balance
      between excitation and inhibition. This balance is particularly important for
      auditory neurons in the lateral superior olive, because these compare excitatory
      inputs from one ear and inhibitory inputs from the other ear to compute sound
      source location. By applying GABA(B) receptor antagonists during sound
      stimulation in vivo, it was revealed that these neurons adjust their binaural
      sensitivity through GABA(B) receptors. Using an in vitro approach, we then
      demonstrate that these neurons release GABA during spiking activity.
      Consequently, GABA differentially regulates transmitter release from the
      excitatory and inhibitory terminals via feedback to presynaptic GABA(B)
      receptors. Modulation of the synaptic input strength, by putative retrograde
      release of neurotransmitter, may enable these auditory neurons to rapidly adjust
      the balance between excitation and inhibition, and thus their binaural
      sensitivity, which could play an important role as an adaptation to various
      listening situations.

PMID- 18614035
TI  - Neuronal ensemble bursting in the basal forebrain encodes salience irrespective
      of valence.
AB  - Both reward- and punishment-related stimuli are motivationally salient and
      attract the attention of animals. However, it remains unclear how motivational
      salience is processed in the brain. Here, we show that both reward- and
      punishment-predicting stimuli elicited robust bursting of many noncholinergic
      basal forebrain (BF) neurons in behaving rats. The same BF neurons also responded
      with similar bursting to primary reinforcement of both valences. Reinforcement
      responses were modulated by expectation, with surprising reinforcement eliciting
      stronger BF bursting. We further demonstrate that BF burst firing predicted
      successful detection of near-threshold stimuli. Together, our results point to
      the existence of a salience-encoding system independent of stimulus valence. We
      propose that the encoding of motivational salience by ensemble bursting of
      noncholinergic BF neurons may improve behavioral performance by affecting the
      activity of widespread cortical circuits and therefore represents a novel
      candidate mechanism for top-down attention.

PMID- 18614036
TI  - Cellular mechanisms underlying stimulus-dependent gain modulation in primary
      visual cortex neurons in vivo.
AB  - Gain modulation is a widespread neuronal phenomenon that modifies response
      amplitude without changing selectivity. Computational and in vitro studies have
      proposed cellular mechanisms of gain modulation based on the postsynaptic effects
      of background synaptic activation, but these mechanisms have not been studied in
      vivo. Here, we used intracellular recordings from cat primary visual cortex to
      measure neuronal gain while changing background synaptic activity with visual
      stimulation. We found that increases in the membrane fluctuations associated with
      increases in synaptic input do not obligatorily result in gain modulation in
      vivo. However, visual stimuli that evoked sustained changes in resting membrane
      potential, input resistance, and membrane fluctuations robustly modulated
      neuronal gain. The magnitude of gain modulation depended critically on the
      spatiotemporal properties of the visual stimulus. Gain modulation in vivo may
      thus be determined on a moment-to-moment basis by sensory context and the
      consequent dynamics of synaptic activation.

PMID- 18614037
TI  - Prefrontal coding of temporally discounted values during intertemporal choice.
AB  - Reward from a particular action is seldom immediate, and the influence of such
      delayed outcome on choice decreases with delay. It has been postulated that when
      faced with immediate and delayed rewards, decision makers choose the option with
      maximum temporally discounted value. We examined the preference of monkeys for
      delayed reward in an intertemporal choice task and the neural basis for real-time
      computation of temporally discounted values in the dorsolateral prefrontal
      cortex. During this task, the locations of the targets associated with small or
      large rewards and their corresponding delays were randomly varied. We found that
      prefrontal neurons often encoded the temporally discounted value of reward
      expected from a particular option. Furthermore, activity tended to increase with
      [corrected] discounted values for targets [corrected] presented in the neuron's
      preferred direction, suggesting that activity related to temporally discounted
      values in the prefrontal cortex might determine the animal's behavior during
      intertemporal choice.

PMID- 18614038
TI  - Differential neural activation for updating rule versus stimulus information in
      working memory.
AB  - Establishing what information is actively maintained in working memory (WM) and
      how it is represented and controlled is essential to understanding how such
      information guides future behavior. WM has traditionally been investigated in
      terms of the maintenance of stimulus-specific information, such as locations or
      words. More recently, investigators have emphasized the importance of rules that
      establish relationships between those stimuli and the pending response. The
      current study used a mental arithmetic task with fMRI to test whether updating of
      numbers (i.e., stimuli) and updating of mathematical operations (i.e., rules) in
      WM relies on the same neural system. Results indicate that, while a common
      network is activated by both types of updating, rule updating preferentially
      activates prefrontal cortex while number updating preferentially activates
      parietal cortex. The results suggest that both numbers and rules are maintained
      in WM but that they are different types of information that are controlled
      independently.

PMID- 18614039
TI  - Dun1 counts on rad53 to be turned on.
AB  - In a recent issue of Molecular Cell, Lee et al. (2008) demonstrate that the
      forkhead-associated (FHA) domain of Dun1, a Chk2-related kinase involved in DNA
      damage signaling, selectively binds a diphosphorylated motif found in its paralog
      and upstream regulator Rad53.

PMID- 18614040
TI  - Just the FACTs: histone H2B ubiquitylation and nucleosome dynamics.
AB  - In this issue of Molecular Cell, Fleming et al. (2008) show that histone H2B
      ubiquitylation and FACT function interdependently to facilitate nucleosome
      reassembly during transcription elongation, thereby demonstrating that histone
      posttranslational modifications can provide important but transient
      transcriptional signaling cues.

PMID- 18614041
TI  - Getting the message out.
AB  - In a recent issue of Molecular Cell, Schwer (2008) demonstrates that, during the
      latest stage of the splicing reaction, the RNA-dependent helicase Prp22 is
      deposited upon the downstream exon, where it subsequently strips the spliced
      messenger RNA from the spliceosome.

PMID- 18614042
TI  - mTOR and Akt signaling in cancer: SGK cycles in.
AB  - In a recent issue of Molecular Cell, Hong et al. (2008) describe an alternative
      mechanism by which mTOR promotes cell-cycle progression; it phosphorylates and
      activates SGK, which in turn phosphorylates the cell-cycle inhibitor p27,
      promoting its cytoplasmic retention.

PMID- 18614043
TI  - Nucleotide excision repair driven by the dissociation of CAK from TFIIH.
AB  - The transcription/DNA repair factor TFIIH is organized into a core that
      associates with the CDK-activating kinase (CAK) complex. Using chromatin
      immunoprecipitation, we have followed the composition of TFIIH over time after UV
      irradiation of repair-proficient or -deficient human cells. We show that TFIIH
      changes subunit composition in response to DNA damage. The CAK is released from
      the core during nucleotide excision repair (NER). Using reconstituted in vitro
      NER assay, we show that XPA catalyzes the detachment of the CAK from the core,
      together with the arrival of the other NER-specific factors. The release of the
      CAK from the core TFIIH promotes the incision/excision of the damaged
      oligonucleotide and thereby the repair of the DNA. Following repair, the CAK
      reappears with the core TFIIH on the chromatin, together with the resumption of
      transcription. Our findings demonstrate that the composition of TFIIH is dynamic
      to adapt its engagement in distinct cellular processes.

PMID- 18614044
TI  - Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage.
AB  - The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the
      DNA-damage response, an inducible process required for the suppression of
      malignancy. The Mre11 complex is predominantly required for repair and checkpoint
      activation in S phase, whereas Chk2 governs apoptosis. We examined the
      relationship between the Mre11 complex and Chk2 in the DNA-damage response via
      the establishment of Nbs1(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/ATLD1) Chk2(-/
      ) mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal
      instability of Mre11 complex mutants; however, the double-mutant mice exhibited
      synergistic defects in DNA-damage-induced p53 regulation and apoptosis.
      Nbs1(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/ATLD1) Chk2(-/-) mice were also
      predisposed to tumors. In contrast, DNA-PKcs-deficient mice, in which G1-specific
      chromosome breaks are present, did not exhibit synergy with Chk2(-/-) mutants.
      These data suggest that Chk2 suppresses the oncogenic potential of DNA damage
      arising during S and G2 phases of the cell cycle.

PMID- 18614045
TI  - A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA
      replication.
AB  - The histone H2A variant H2AX is rapidly phosphorylated in response to DNA double
      stranded breaks to produce gamma-H2AX. gamma-H2AX stabilizes cell-cycle
      checkpoint proteins and DNA repair factors at the break site. We previously found
      that the protein phosphatase PP2A is required to resolve gamma-H2AX foci and
      complete DNA repair after exogenous DNA damage. Here we describe a three-protein
      PP4 phosphatase complex in mammalian cells, containing PP4C, PP4R2, and
      PP4R3beta, that specifically dephosphorylates ATR-mediated gamma-H2AX generated
      during DNA replication. PP4 efficiently dephosphorylates gamma-H2AX within
      mononucleosomes in vitro and does not directly alter ATR or checkpoint kinase
      activity, suggesting that PP4 acts directly on gamma-H2AX in cells. When the PP4
      complex is silenced, repair of DNA replication-mediated breaks is inefficient,
      and cells are hypersensitive to DNA replication inhibitors, but not radiomimetic
      drugs. Therefore, gamma-H2AX elimination at DNA damage foci is required for DNA
      damage repair, but accomplishing this task involves distinct phosphatases with
      potentially overlapping roles.

PMID- 18614046
TI  - The kleisin subunit of cohesin dictates damage-induced cohesion.
AB  - Cohesin, the protein complex that mediates sister chromatid cohesion, is required
      for faithful chromosome segregation and efficient repair of double-strand breaks
      (DSBs). Cohesion generation is normally restricted to S phase. However, in G2/M,
      a DSB activates cohesion generation near the DSB and genome-wide. Here, using
      budding yeast, we show that DSB-induced cohesion occurs when cohesin contains the
      kleisin subunit, Mcd1 (Scc1), but not when Mcd1 is replaced by its meiotic
      isoform, Rec8. We exploit this divergence to demonstrate that serine 83 of Mcd1
      and the Chk1 kinase are critical determinants for DSB-induced cohesion. We
      propose that a DSB in G2/M activates Mec1 (ATR), which in turn stimulates Chk1
      dependent phosphorylation of Mcd1 at serine 83. Serine 83 phosphorylation
      promotes chromatin-bound cohesin to become cohesive.

PMID- 18614047
TI  - H2B ubiquitylation plays a role in nucleosome dynamics during transcription
      elongation.
AB  - The monoubiquitylation of histone H2B has been associated with transcription
      initiation and elongation, but its role in these processes is poorly understood.
      We report that H2B ubiquitylation is required for efficient reassembly of
      nucleosomes during RNA polymerase II (Pol II)-mediated transcription elongation
      in yeast. This role is carried out in cooperation with the histone chaperone
      Spt16, and in the absence of H2B ubiquitylation and functional Spt16, chromatin
      structure is not properly restored in the wake of elongating Pol II. Moreover,
      H2B ubiquitylation and Spt16 play a role in each other's regulation. H2B
      ubiquitylation is required for the stable accumulation of Spt16 at the GAL1
      coding region, and Spt16 regulates the formation of ubiquitylated H2B both
      globally and at the GAL1 gene. These data provide a mechanism linking H2B
      ubiquitylation to Spt16 in the regulation of nucleosome dynamics during
      transcription elongation.

PMID- 18614048
TI  - Nuclear mRNA surveillance in THO/sub2 mutants is triggered by inefficient
      polyadenylation.
AB  - The yeast THO complex and the associated RNA helicase Sub2p are important mRNP
      maturation factors. Transcripts produced in THO/sub2 mutants are subject to
      degradation by a surveillance mechanism that involves the nuclear RNA exosome.
      Here we show that inefficient polyadenylation forms the basis of this accelerated
      mRNA decay. A genetic screen reveals extensive interactions between deletions of
      THO subunits and mRNA 3' end processing mutants. Nuclear run-ons strengthen this
      link by showing premature transcription termination close to polyadenylation
      sites in THO/sub2 mutants in vivo. Moreover, in vitro, pre-mRNA substrates are
      poorly polyadenylated and consequently unstable in extracts from THO/sub2 mutant
      strains. Decreased polyadenylation correlates with a specific downregulation of
      the poly(A)-polymerase cofactor Fip1p by the ubiquitin/proteasome pathway. Both
      polyadenylation defects and Fip1p instability depend on the nuclear exosome
      component Rrp6p and its activator Trf4p. We suggest that removal of aberrant mRNA
      is facilitated by direct regulation of polyadenylation activity.

PMID- 18614049
TI  - The nuclear exosome and adenylation regulate posttranscriptional tethering of
      yeast GAL genes to the nuclear periphery.
AB  - GAL genes and other activated yeast genes remain tethered to the nuclear
      periphery even after transcriptional shutoff. To identify factors that affect
      this tethering, we designed a plasmid-based visual screen. Although many factors
      affected GAL tethering during transcription, fewer specifically affected
      posttranscriptional tethering. Tw o of these, Rrp6p and Lrp1p, are nuclear
      exosome components known to contribute to RNA retention near transcription sites
      (dot RNA). Moreover, these exosome mutations lead to a substantial
      posttranscriptional increase in polyadenylated GAL1 3' ends. This accompanies a
      loss of unadenylated (pA-) GAL1 RNA and a loss of posttranscriptional gene
      periphery tethering, as well as a decrease in dot RNA levels. This suggests that
      the exosome inhibits adenylation of some GAL1 transcripts, which results in the
      accumulation of pA- RNA adjacent to the GAL1 gene. We propose that this dot RNA,
      probably via RNP proteins, contributes to the physical tether linking the GAL1
      gene to the nuclear periphery.

PMID- 18614050
TI  - Different aa-tRNAs are selected uniformly on the ribosome.
AB  - Ten E. coli aminoacyl-tRNAs (aa-tRNAs) were assessed for their ability to decode
      cognate codons on E. coli ribosomes by using three assays that evaluate the key
      steps in the decoding pathway. Despite a wide variety of structural features,
      each aa-tRNA exhibited similar kinetic and thermodynamic properties in each
      assay. This surprising kinetic and thermodynamic uniformity is likely to reflect
      the importance of ribosome conformational changes in defining the rates and
      affinities of the decoding process as well as the evolutionary "tuning" of each
      aa-tRNA sequence to modify their individual interactions with the ribosome at
      each step.

PMID- 18614052
TI  - Kinase activation and transformation by NUP214-ABL1 is dependent on the context
      of the nuclear pore.
AB  - Genetic alterations causing constitutive tyrosine kinase activation are observed
      in a broad spectrum of cancers. Thus far, these mutant kinases have been
      localized to the plasma membrane or cytoplasm, where they engage proliferation
      and survival pathways. We report that the NUP214-ABL1 fusion is unique among
      these because of its requisite localization to the nuclear pore complex for its
      transforming potential. We show that NUP214-ABL1 displays attenuated transforming
      capacity as compared to BCR-ABL1 and that NUP214-ABL1 preferentially transforms T
      cells, which is in agreement with its unique occurrence in T cell acute
      lymphoblastic leukemia. Furthermore, NUP214-ABL1 differs from BCR-ABL1 in
      subcellular localization, initiation of kinase activity, and signaling and lacks
      phosphorylation on its activation loop. In addition to delineating an unusual
      mechanism for kinase activation, this study provides new insights into the
      spectrum of chromosomal translocations involving nucleoporins by indicating that
      the nuclear pore context itself may play a central role in transformation.

PMID- 18614051
TI  - Structural basis for the autoinhibition of talin in regulating integrin
      activation.
AB  - Activation of heterodimeric (alpha/beta) integrin transmembrane receptors by the
      270 kDa cytoskeletal protein talin is essential for many important cell adhesive
      and physiological responses. A key step in this process involves interaction of
      phosphotyrosine-binding (PTB) domain in the N-terminal head of talin (talin-H)
      with integrin beta membrane-proximal cytoplasmic tails (beta-MP-CTs). Compared to
      talin-H, intact talin exhibits low potency in inducing integrin activation. Using
      NMR spectroscopy, we show that the large C-terminal rod domain of talin (talin-R)
      interacts with talin-H and allosterically restrains talin in a closed
      conformation. We further demonstrate that talin-R specifically masks a region in
      talin-PTB where integrin beta-MP-CT binds and competes with it for binding to
      talin-PTB. The inhibitory interaction is disrupted by a constitutively activating
      mutation (M319A) or by phosphatidylinositol 4,5-bisphosphate, a known talin
      activator. These data define a distinct autoinhibition mechanism for talin and
      suggest how it controls integrin activation and cell adhesion.

PMID- 18614054
TI  - Enhanced interferon production from chick embryo cells aged in in vitro.
AB  - The plaque-forming efficiency of Sindbis virus decreased as much as 1000-fold,
      and plaque size was diminished markedly, when tested on chick embryo cell
      monolayers aged in vitro. The plaquing efficiency and plaque size of Newcastle
      disease virus was unaffected. The reaction(s) associated with aging in vitro
      which lead to lowered plaquing efficiency are slowed considerably when cell
      monolayers are: (1) established in Simpson-Hirst medium rather than standard
      growth medium; (2) held at 31 degrees ; (3) given a regimen of daily medium
      changes; or (4) trypsinized and used as young secondary cultures. A loss in the
      average yield of virus per cell accompanies the loss in plaquing efficiency of
      Sindbis virus on aged monolayers. Adding actinomycin D to the aged cells at the
      time of infection eliminated completely the inhibition of Sindbis virus
      replication. Cells aged for 7 days in vitro were found to produce up to 32 times
      more interferon than cells 1-2 days old and were more sensitive to the action of
      interferon. The decrease in efficiency of Sindbis virus plaquing and yield in
      aged cells is accounted for by their development of an enhanced capacity to
      synthesize interferon upon appropriate stimulation. The process of contact
      inhibition and its concomitant regulation of macromolecular synthesis seems
      implicated in the aging phenomenon in that it may produce a generalized state of
      "enhanced derepressibility" in the cell.

PMID- 18614053
TI  - Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in
      both human and yeast.
AB  - Sister chromatid cohesion is normally established in S phase in a process that
      depends on the cohesion establishment factor Eco1, a conserved acetyltransferase.
      However, due to the lack of known in vivo substrates, how Eco1 regulates cohesion
      is not understood. Here we report that yeast Eco1 and its human ortholog, ESCO1,
      both acetylate Smc3, a component of the cohesin complex that physically holds the
      sister chromatid together, at two conserved lysine residues. Mutating these
      lysine residues to a nonacetylatable form leads to increased loss of sister
      chromatid cohesion and genome instability in both yeast and human. In addition,
      we clarified that the acetyltransferase activity of Eco1 is essential for its
      function. Our study thus identified a molecular target for the acetyltransferase
      Eco1 and revealed that Smc3 acetylation is a conserved mechanism in regulating
      sister chromatid cohesion.

PMID- 18614055
TI  - Streptomycin suppression of ambivalent phage mutations.
AB  - Phenotypic repair by streptomycin has been studied in amber mutants of phage T4
      on su- strains, as has the interference of SmR mutations with amber suppressors.
      The repair seems not to be specific; however a temporal specificity of
      streptomycin action has been demonstrated by means of pulse experiments. The
      dependence of the efficiency of suppression upon experimental condition is also
      reported.

PMID- 18614056
TI  - Mutations in bacteriophage lambda affecting host cell lysis.
AB  - Nine temperature-sensitive and defective mutants of phage lambda deficient in
      lysis of the host cell have been analyzed in respect to location of the site of
      mutation and phenotypic properties. Seven of the isolates are mutant in cistron R
      and produce either a thermolabile endolysin or no detectable enzyme. The
      remaining two mutants, one temperature-sensitive and one defective, produce high
      levels of apparently normal enzyme. These mutants denote the involvement of at
      least one phage cistron other than R in the lytic process.

PMID- 18614057
TI  - Effects of aster yellows virus infection on transport through plant stem
      sections.
AB  - Basipetal transport of various substances through half-inch stem sections of
      healthy and aster yellows virus-infected Nicotiana rustica L. var. humilis was
      determined. The effects of infection by three strains of the virus, dwarf,
      severe, and Tulelake were observed on the transport of 14C-labeled beta
      indoleacetic acid, malic acid, succinic acid, sucrose, glucose, mannose, and the
      ions sulfate, phosphate, and rubidium. Transport of all these substances except
      phosphate ion was more rapid through diseased than through healthy stem sections.
      In the dark, and with supplementary auxin, transport of phosphate ion was also
      more rapid through diseased than through healthy stem sections. Transport of beta
      indoleacetic acid and of sugars through healthy stem sections was more rapid in
      the dark than in the light, but transport of these compounds through diseased
      stem sections was unaffected by light. No appreciable chemical conversion of the
      substances tested was observed during the transport time used.

PMID- 18614058
TI  - Effect of tobacco mosaic virus infection on glucose metabolism in Nicotiana
      tabacum var. Samsun. III. Investigation of hexosemonophosphate shunt enzymes and
      steroid concentration and biosynthesis.
AB  - Activity of the enzymes phosphoriboisomerase, glucose-6-phosphate and 6
      phosphogluconic acid dehydrogenases were assayed in healthy and TMV-infected
      roots of Nicotiana tabacum L. var. Samsun plants grown in nutrient culture. The
      results indicate that all enzymes were equally active in both infected and
      healthy tissues. Endogenous sterol concentration in TMV-infected and healthy N.
      tabacum leaves, stems, and roots were investigated. Sterol biosynthesis was
      studied by infusing mevalonic acid-2-14C (MVA-14C) into TMV-infected and healthy
      tissues and isolating the sterol fraction by silicic acid column chromatography.
      The component sterols of the total sterol fraction were identified by gas-liquid
      chromatography. Infection with TMV had no effect on the level of sterols in
      roots, stems or leaves. Healthy and TMV-infected plants were not significantly
      different in their ability to synthesize sterols from MVA-14C. Cholesterol,
      campesterol, stigmasterol, and beta-sitosterol were identified as the major
      constituents of the total sterol fraction from stem and leaf tissues.

PMID- 18614059
TI  - Electron microscopy of leaves infected with sowbane mosaic virus and other small
      polyhedral viruses.
AB  - Leaves of Chenopodium amaranticolor were infected with sowbane mosaic virus
      (SMV), sectioned and examined by electron microscopy. Leaves of Brassica
      pekinensis and C. amaranticolor were infected with turnip yellow mosaic virus and
      cowpea mosaic virus, respectively, and similarly studied. With all three viruses
      it was difficult, in sections, to distinguish the small isometric virus particles
      from ribosomes though sometimes this was possible, especially when the viruses
      crystallized. Pretreatment of tissue with permanganate or EDTA appeared to
      destroy the ribosomes but resulted in excessive disorganization of the tissue.
      Although SMV did not normally crystallize, wilting the infected leaves caused it
      to do so. All three viruses were found free in the cytoplasm and were absent from
      nuclei, chloroplasts, and mitochondria. Some abnormal structures found in the
      infected tissues are described.

PMID- 18614060
TI  - Some biological and physicochemical properties of blue-green algal virus LPP-1.
AB  - Adsorption and one-step growth experiments performed with blue-green algal virus
      (BGAV) LPP-1 under normal conditions revealed a slow adsorption rate, in
      comparison with bacteriophage systems, followed by a 7-hour latent period. The
      burst size was approximately 100 virus particles per cell. The molecular weight
      of the virus obtained from sedimentation and diffusion measurements was 51 +/- 3
      x 10(6) daltons, and the hydration was calculated to be 0.37 g of H2O per gram of
      virus. Phosphorus analysis indicated a DNA content of 40% w/w, while amino acid
      analysis revealed all the common amino acids to be present. At reduced magnesium
      concentrations, the virus breaks apart, liberating its DNA, which then can be
      separated from the protein by sedimentation in a CsCl density gradient. A protein
      component was obtained as ghosts. Neutralization experiments with BGAV antiserum
      established no relationship to bacteriophages T1, T2, or T3.

PMID- 18614061
TI  - Physical properties of the DNA from the blue-green algal virus LPP-1.
AB  - Deoxyribonucleic acid extracted from BGAV LPP-1 is double-stranded and has a base
      composition of 55% guanine plus cytosine. Sedimentation analysis indicated that
      the DNA is monodisperse with a molecular weight of 25 +/- 2 million, based on
      comparison with T7 DNA.

PMID- 18614062
TI  - Multiplication in Serratia of a bacteriophage originating from Escherichia coli:
      lysogenization and host-controlled variation.
AB  - Temperate bacteriophage P2, originally obtained from Escherichia coli strain
      Lisbonne, and usually grown on E. coli or Shigella strains, is also able to
      multiply in some Serratia strains. One of these has been shown to give stable
      lysogenic derivatives upon P2 infection. In passing from E. coli to Serratia and
      vice versa, P2 undergoes host-controlled variation. The base ratio in the DNA of
      the Serratia strain used is typical of Serratia strains (59% GC content) whereas
      that of P2 DNA (50% GC content) is like that of E. coli DNA, even after the phage
      has been grown in the Serratia host. Serratia bacteria lysogenic for P2 do not
      seem to contain numerous P2 DNA equivalents. The accidental formation of
      identical base pair sequences in DNA's of similar or different base ratios is
      discussed in the appendix.

PMID- 18614063
TI  - Fractionation of the complementary strands of coliphage lambda DNA based on the
      asymmetric distribution of the poly I,G-binding sites.
AB  - Poly I,G interacts preferentially with one of the two complementary DNA strands
      of lambda and lambda-related phages 21, 434, and phi80, thus permitting
      preparative separation of the "dense" fraction, consisting of a complex between
      the intact strands C and poly I,G, from the less dense ("light") fraction
      containing the intact strands W, which bind 3-4 times less poly I,G. The isolated
      and self-annealed fractions are over 99% pure as far as their hybridization
      properties with complementary RNA are concerned. The interaction of poly I,G with
      intact and fragmented DNA of lambda and its deletion mutants could be interpreted
      as indicating the asymmetric distribution of poly I,G-binding deoxycytidine-(dC)
      rich clusters between the strands of lambda DNA; on the left arm (55% G + C) the
      dC-clusters seem to be restricted to the C strand, whereas both complementary
      strands of the right arm (46% G + C) of lambda DNA contain these dC clusters.
      Thus, the two arms of lambda DNA differ not only in their average base
      composition (Hershey, 1966), but also in the mode of distribution of the dC-rich
      clusters, the latter possibly related to the initiation, termination and
      orientation of the DNA-to-RNA transcription from the complementary DNA strands.

PMID- 18614064
TI  - Studies on P2 prophage-host relationships. I. Alteration of P2 prophage
      localization patterns in Escherichia coli by interstrain transduction.
AB  - The linkage of P2 prophage location I in Escherichia coli C and location H in E.
      coli K with the histidine operon has been confirmed. Evidence is presented that
      alteration of the histidine region of the chromosome of E. coli K and E. coli C
      strains can result in alteration of the pattern of localization of P2 prophage.

PMID- 18614065
TI  - Studies on a temperature-sensitive step essential to herpesvirus DNA replication.
AB  - The nature of a previously described (Stevens, 1966) heat-sensitive step
      essential to the replication of infectious bovine rhinotracheitis virus
      deoxyribonucleic acid has been investigated. By temperature "shift down"
      experiments, the step was found to occur 1 hour after infection. In addition, the
      virus was shown to induce increased activity of a unique DNA polymerase at both
      37 degrees and 42 degrees. These results, when coupled with previous data,
      suggest that the heat-sensitive step is concerned with an essential change either
      in the intracellular location or in the physical state of the infecting DNA
      molecule.

PMID- 18614066
TI  - Electron microscopic investigations of the interaction between the T2-phage and
      its IgG-and IgM-antibodies.
AB  - The morphology of the antigenic T2 bacteriophage, when complexed with its IgG and
      IgM antibodies, was investigated with the aid of the electron microscope. The
      surface of T2 contains at least two distinct antigenic substances located at the
      head membrane and at the tail. Antibodies directed against the antigenic head
      membrane formed bridges between two adjacent phage heads. IgG antibodies were
      observed combined by one of their short ends to the head membrane, and tangles of
      antibody molecules were sometimes noted on the head membrane. A combining site of
      the IgM antibody linked to a phage head was occasionally detected. Neutralizing
      antibodies against T2 reacted with the distal portion of the phage tails. A few
      IgM antibody molecules were found which appeared to plug the tail base plate.
      Tail fibers of T2 were prepared and injected into rabbits for production of
      specific, neutralizing antibodies. One percent IgG antifiber antibody had a
      neutralization rate constant, K, around 290, and 0.2% IgM antifiber antibody had
      an average K value of 1.9. Those specific, neutralizing antibodies were detected
      at the tail fibers of neutralized T2 phages.

PMID- 18614067
TI  - The disaggregation of host polyribosomes in productive and abortive infection
      with herpes simplex virus.
AB  - Herpes simplex virus strain MPdk- causes disaggregation of host polyribosomes in
      both permissive (HEp-2) and nonpermissive (DK) cells during the first 3 hours
      after infection. The following findings are discussed in this paper: (1) UV light
      irradiated virus does not cause disaggregation of host polyribosome. (2) To
      obtain equivalent disaggregation of host polyribosomes, 1 hour after infection
      the nonpermissive DK cells must be infected with MPdk- virus at a multiplicity
      twenty- to thirty-fold higher than the permissive HEp-2 cells. (3) Actinomycin D
      (0-20 microg/ml of medium), 6-azauridine (0-10(-4) M), or p-fluorophenylalanine
      (0-10(-3) M) do not prevent the disaggregation of host polyribosomes in HEp-2
      cells infected with 60 plaque-forming units (PFU)/cell of MPdk- virus. However,
      the drugs do prevent the disaggregation of host polyribosomes in DK cells
      infected with 1000 PFU/cell of MPdk- virus. (4) The differences between HEp-2 and
      DK cells with respect to multiplicity requirements to induce disaggregation and
      the ability of the drugs to prevent it are due to some property of the product
      specified by MPdk- in these cells. This conclusion is based on the finding that
      in DK cells productively infected with MPdk+sp, a multistep mutant of MPdk-
      virus, equivalent disaggregation of host polyribosomes is achieved with 40
      PFU/cell and cannot be prevented by actinomycin D. The interpretation of these
      findings is based on data reported previously that the products specified by MPdk
      virus in nonpermissive DK cells malfunction. We conclude that (1) in permissive
      cells the disaggregation of host polyribosomes is catalyzed by a highly efficient
      protein synthesized after infection; (2) in nonpermissive cells the protein
      malfunctions; to obtain comparable reduction in host functions the concentration
      of this protein must be higher in nonpermissive cells. This condition is
      satisfied by infecting nonpermissive cells at high multiplicity. (3) The
      reduction in synthesis or in function of this protein by the various drugs is
      sufficient to prevent the breakdown of host polyribosomes in nonpermissive cells
      but not in permissive cells.

PMID- 18614068
TI  - Effects of uncouplers of oxidative phosphorylation on the infection of
      Escherichia coli K12 by phage-lambda DNA.
AB  - Some effects of two uncouplers of oxidative phosphorylation on infection of
      Escherichia coli K12 by bacteriophage lambda deoxyribonucleic acid (DNA) are
      described. Dinitrophenol did not interfere with the initial interaction of the
      cells with free DNA, and neither dinitrophenol nor carbonyl cyanide m
      chlorophenylhydrazone affected the linear portion of the infection reaction.
      However, the process by which lambda-DNA bound to the bacterial cell became
      insensitive to deoxyribonuclease was strongly inhibited by both uncoupling
      agents. These results support the conclusion that successful infection of E. coli
      with phage lambda-DNA is coupled to cellular energy metabolism and localize a
      portion of the infection reaction which is sensitive to the uncoupling of
      oxidative phosphorylation. Possible energy-requiring steps in the infection
      process are discussed.

PMID- 18614069
TI  - Composition of artificially produced and naturally occurring empty capsids of
      poliovirus type 1.
AB  - The polypeptide composition of the empty capsids of poliovirus type 1 represented
      either by the 73 S component isolated from sucrose gradients or by the top
      component from CsCl gradients is different from that ot the whole infectious
      virion. One protein (VP4) is absent from the empty capsids, another (VP2) is
      lower in relative amount, while an additional protein (NCVP6), not present in
      purified virions, is found in large amounts. Artificial production of 73 S
      particles by borate buffer, pH 10.5, treatment of purified virions results in
      removal of one protein component (VP4) and the RNA of the virus. The observed
      differences in composition of these virus-specific particles are discussed with
      regard to their possible role in the architecture and the assembly of the virion.

PMID- 18614070
TI  - The mechanism of genetic resistance of chick embryo cells to infection by Rous
      sarcoma virus-Bryan strain (BS-RSV).
AB  - The early steps of Rous sarcoma virus-Bryan strain (BS-RSV) infection of
      genetically resistant and susceptible chick embryo cells were investigated. The
      methods used were the uptake of virus by cells grown in monolayer, and the
      ability of infected cells to form foci of transformed cells after plating on
      resistant and susceptible assay plates. It was found that the initial attachment
      of virus to either genetic type of cells did not differ appreciably. Attachment
      on susceptible cells was immediately followed by penetration, which was 70%
      complete after 1 hour. Attachment on resistant cells was not followed by
      penetration of the cell membrane. It was concluded that the genetic block of
      resistance to infection of chick embryo cells by BS-RSV occurs at the step of
      viral penetration of the cell membrane.

PMID- 18614071
TI  - Phenotypic mixing in the avian tumor virus group.
AB  - Mixed infection of chick embryo fibroblasts with avian tumor viruses of subgroups
      A and B yields progeny virus in which properties of both parental subgroups are
      combined. Such combination forms of avian tumor virus have an expanded host range
      on genetically resistant chicken cells. This allows virus particles with a
      subgroup A genome to enter into C A cells from which subgroup A virus is
      otherwise excluded. Likewise, mixedly grown virus particles with a subgroup B
      genome can be shown to replicate in C B cells which are insusceptible to pure
      subgroup B stocks. The ability of combination forms to overcome host range
      barriers appears to result from the presence of subgroup A and B envelope
      antigens in individual virus particles. Neutralization experiments with antibody
      also indicate that the envelope of many mixedly grown avian tumor virus particles
      contains a mosaic of A and B antigens. Chicken serum specific against subgroup A
      envelope antigen prevents subgroup B genomes in mixedly grown virus from entering
      C B cells. Conversely, anti B serum neutralizes infectivity of subgroup A genomes
      on C A cells. The combination of subgroup A and B characteristics in particles of
      mixedly grown avian tumor virus preparations is genetically unstable at low
      multiplicities of infection. Most of the combination forms appear to be caused by
      phenotypic mixing but the occurrence of heterozygotes or of a small percentage of
      recombinants cannot be excluded.

PMID- 18614072
TI  - A nuclease specific for double-stranded RNA.

PMID- 18614073
TI  - Spontaneous virus production from "non-virus producing" Rous sarcoma cells.

PMID- 18614074
TI  - Intracellular crystallization of the DNA coliphage N4.

PMID- 18614075
TI  - Immunofluorescent demonstration of a specific surface antigen in cells infected
      or transformed by polyoma virus.

PMID- 18614076
TI  - The effect of deoxyribonuclease on the synthesis of DNA of vaccinia virus.

PMID- 18614077
TI  - An investigation of bacteriophage lambda, its protein ghosts and subunits.
AB  - The sedimentation coefficients and molecular weights of bacteriophage lambda and
      its ghost were determined as So(20,w) = 416 x 10(-13) second and M = 57 x 10(6)
      for the virus, and So(20,w) = 141 x 10(-13) second and M = 21 x 10(6) for the
      ghost. The protein portion of the virus consists of at least two distinct types
      of subunits, with molecular weights of 55,000 and 110,000, which differ markedly
      in their amino acid content.

PMID- 18614078
TI  - Early events in the infection process of adenovirus type 5 in HeLa cells.
AB  - The fate of adenovirus type 5r after infection of HeLa cells has been studied
      with the help of purified labeled virus preparations. The infection process
      starts with the adsorption of virions on the cell surface followed by penetration
      into the cells. Shortly after penetration, the particles inside the cells have a
      similar appearance as intact virions. However, a small amount of protein must
      have been lost, as concluded from radioactivity measurements and from the change
      in buoyant density (1.35 g/cm(3) instead of 1.34 g/cm(3), the value for intact
      virions). Evidence is presented that antigen B is absent from the 1.35-particles.
      After the transformation of virions into 1.35-particles, further uncoating leads
      to the formation of DNase-sensitive DNA-protein complexes. The proteins released
      during the uncoating show a buoyant density of 1.31 g/cm(3) and are almost
      completely insoluble in acid. No extensive breakdown of protein can be detected.
      The processes of attachment, penetration, and uncoating are not inhibited by
      prevention of de novo protein synthesis, as could be shown with cycloheximide.

PMID- 18614079
TI  - Infectivity expression of a carrier cell line HeLa/HA2.
AB  - A culture of HeLa cells persistently infected with hemadsorption type 2 virus,
      designated as HeLa/HA2, was studied for its infectivity expression and cloning
      efficiency. The infectivity titer of cell suspensions approximates the number of
      carrier cells and is also approximately equal to the number of cells able to form
      clones. Very few virions are released into the medium. Both host and viral
      genomes can thus express themselves within each carrier cell. Studies to
      determine the mechanism by which virus passed from carrier to indicator cells
      revealed that the continued presence of antiviral serum prevented transmission.
      In contrast, treatment of carrier cells with the viral specific serum for an
      interval of less than 2 days followed by washing, did not inhibit transmission of
      the virus to monkey kidney cells. Therefore, successful transmission of
      infectivity from these carrier cells must frequently require more than 2 days of
      incubation.

PMID- 18614080
TI  - Specific interference among strains of Newcastle disease virus. I. Demonstration
      and measurement of the interference.
AB  - A non-plaque-forming vaccine strain of NDV (NDV-B1) interferes with the infection
      of cultured chick embryo cells by the virulent plaque-forming NDV-L strain. The
      level of interference increases when the concentration of interfering virus is
      increased or when the time between infection and superinfection is increased.
      Only at multiplicities of superinfection of less than one does one obtain an
      accurate measure of the degree of interference. The direct assay technique for
      measuring the extent of interference is compared with the infective center assay,
      and the superiority of the latter in interference experiments is demonstrated. A
      procedure for plating infective centers is described which insures that the
      majority of plaques formed in the infective center assay are due to infected
      cells and not reversibly attached or free virus.

PMID- 18614081
TI  - Kinetics of quinone inactivation of Tulare apple mosaic virus.
AB  - A direct assay technique was used to measure the kinetics of o-quinone
      inactivation of Tulare apple mosaic virus (TAMV). Inactivation occurred at rates
      measurable in seconds, minutes, or hours depending upon the particular quinone
      tested and the ratio of benzoquinone equivalents per milligram of virus used. The
      inactivation rate appeared independent of the absolute virus concentration.
      Inactivation rates were not linear at any quinone concentration measurable.
      However, inactivation data plotted according to the equation 1/I = (b/a)(1/t) +
      1/a where I is the percent inactivation, a and b constants, and t exposure time,
      gave linear curves from which initial inactivation rates (percent virus
      inactivated in the first second) and minimum exposure times (times required to
      cause 100% inactivation) could be determined.

PMID- 18614082
TI  - Kinetics of sensitization of herpes simplex virus and its relationship to the
      reduction in the neutralization rate constant.
AB  - Incubation of herpes simplex virus (HSV) with rabbit anti-HSV for as little as
      2.5 minutes rendered 75% of the surviving fraction neutralizable by anti-rabbit
      gamma-globulin antiserum. The degree of this sensitization increased with time
      and at 20 minutes over 99.8% of the surviving virus was sensitized.
      Neutralization kinetics showed that as the degree of sensitization increased, the
      neutralization rate constant decreased. Incubation of HSV with anti-HSV for 5,
      20, and 120 minutes resulted, respectively, in a 23%, 59%, and 87% reduction in
      the neutralization rate constant. These findings suggest that sensitization is an
      important factor in the inhibition of neutralization and the formation of the
      persistent fraction.

PMID- 18614083
TI  - Induction of C(II) and O functions in early defective lambda prophages.
AB  - Defective mutations in the x region of the lambda chromosome abolish the
      expression of both C(II) and O functions. After U.V. irradiation of lysogenic
      bacteria harboring a N defective prophage, C(II) and O products seem to be
      accumulated. These results provide further support for the idea that x, y, C(II),
      and O form an operon that is transcribed from x to O, is directly controlled by
      the immunity repressor and whose expression is not dependent on that of gene N.

PMID- 18614084
TI  - Kern Canyon virus: electron microscopic and immunological studies.
AB  - Kern Canyon virus (KCV), propagated in suckling mouse brain and cell culture, was
      examined by negative contrast and thin section electron microscopy. The virus was
      found to exhibit symmetry similar to other viruses of the Stomatoviridae family.
      The bullet-shaped virus particles had a mean length of 132 micron and were 73
      micron in diameter. Cross striations, axial channels and surface projections were
      prominent. Virus maturation occurred on marginal cytoplasmic membranes with
      mature virions accumulating extracellularly. Complement fixation, virus
      neutralization, and immunodiffusion tests comparing KCV with other bullet-shaped
      viruses of animals confirmed the distinct antigenicity of the virus, whereas
      comparison of KCV with vesicular stomatitis virus in a density gradient
      ultracentrifugation experiment emphasized the physical basis for including KCV
      within the Stomatoviridae family of viruses.

PMID- 18614085
TI  - Phage induction by ultraviolet radiation in strains of Escherichia coli
      possessing and lacking dark repair capacity.
AB  - Prophage induction by ultraviolet light (UV) in strains of Escherichia coli
      possessing and lacking dark repair capacity was investigated. E. coli B and its
      UV-sensitive mutant B(s-1) were lysogenized by temperate phage phi80. Relative
      prophage induction by UV in the two strains paralleled relative UV killing,
      suggesting that prophage induction in a UV-resistant strain is susceptible to
      dark repair. Photoreactivation of induction was observed in B(s-1)(80),
      suggesting that the initial damage for UV induction of prophage in this very
      sensitive strain is due to pyrimidine dimers. No recovery of induction, however,
      was observed in B(80) when the UV-irradiated cells were held in phosphate buffer
      at 37 degrees although there was recovery of cell survival (liquid holding
      recovery). The frequency of spontaneous induction was very much greater in B(s
      1)(80) than in other strains and is one of the highest yet observed in bacteria.
      Although increased sensitivity to UV killing in the logarithmic phase is usually
      seen in lysogenic strains, B(s-1)(80) was not more sensitive to UV killing than
      logarithmic phase B(s-1). Cell division after UV irradiation and before lysis,
      permitting viable cells among the progeny, could account for the lack of extra
      sensitivity in B(s-1)(80). This phenomenon actually was observed microscopically,
      although the mechanism is not understood.

PMID- 18614086
TI  - Studies on the nature of dengue viruses. III. RNA synthesis in cells infected
      with type 2 dengue virus.
AB  - Infection of KB cells with type 2 dengue virus results in stimulation of
      "actinomycin D-resistant" RNA synthesis. The newly synthesized intracellular RNA
      produces plaques on monolayers of BHK21 cells as does RNA extracted from virus.
      The intracellular RNA is composed predominantly of two species with sedimentation
      coefficients of 45 S and 20 S. An intermediate (26 S) form may be present
      occasionally, but then only in barely detectable amounts. The 45 S species
      corresponds to viral RNA. The 20 S RNA is resistant to RNase treatment; after
      denaturation by dimethylsulfoxide its sedimentation coefficient changes to about
      45 S. It is concluded that the 20 S RNA is a double-stranded replicative form. If
      infected cells are exposed to 32P inorganic phosphate early in the viral growth
      cycle, the base composition of the labeled 20 S RNA approaches that expected for
      a double-stranded RNA. If the 32P labeling is done at later periods, however, the
      labeled 20 S base composition is similar to that of the 45 S RNA. It is concluded
      that both strands of the 20 S RNA are synthesized in the early period after
      infection, whereas at later times only the positive or viral strand is
      synthesized.

PMID- 18614087
TI  - The kinetics of yielder cell formation in host-controlled modification caused by
      P1 lysogenic cells.
AB  - The kinetics of yielder cell formation in host-controlled modification mediated
      by prophage P1 has been examined when Escherichia coli strains B(P1) or Bc251(P1)
      are infected with restricted forms of T1, lambda, or P2, respectively. Yielder
      cells are formed by linear kinetics with respect to time for at least 3-5 hours
      after adsorption and incubation. Therefore logarithmically growing cells can hold
      potentially productive genomes of restricted phase in check for long periods of
      time. The majority of yielder cells produce either few or no unrestricted phage.
      Evidence is presented that the probability of yielder cell formation is greater
      than the probability of spontaneous induction of prophage P1. Under similar
      conditions, the relationship between such restricted phage as T1, lambda, or P2
      and nonpermissive cells seems to be identical.

PMID- 18614088
TI  - Enhancement of infectivity by combination of two ribonucleic acid components from
      alfalfa mosaic virus.
AB  - RNA was extracted from alfalfa mosaic virus 425. Infectivity was determined in
      density gradient fractions and in all possible combinations of two fractions.
      Certain combinations were remarkably infectious. This led to the purification
      through two cycles of sucrose gradient centrifugation of a 27 S and a 14 S RNA,
      from bottom component and top component a, respectively. The purified bottom
      component RNA had a low infectivity; when purified top component a RNA was added,
      infectivity increased considerably. Possible explanations for this effect are
      discussed.

PMID- 18614089
TI  - Effect of phage on amino acid activation.
AB  - Infection of Escherichia coli NP2 with T-even phage strains is known to cause the
      appearance of a new valyl tRNA synthetase activity. In the present work mutant
      hosts possessing altered activating enzymes for phenylalanine, glycine, or
      histidine were employed to detect possible phage-induced modifications in the
      translating systems for these amino acids. The results establish that T4 has an
      absolute requirement for the phenylalanyl tRNA synthetase of its host, probably
      in an unmodified form, and that this enzyme is responsible for the incorporation
      of most, if not all, phenylalanine residues into phage protein. Other data
      suggest, less rigorously, that a similar conclusion holds for glycine and
      histidine.

PMID- 18614090
TI  - Initial and subsequent sites of aster yellows virus infection in a leafhopper
      vector.
AB  - Aster yellows virus (AYV) was recovered from hemolymph, alimentary canal,
      salivary glands and ovaries, but not from Malpighian tubules, mycetomes, fat
      body, testes, or brain of viruliferous leafhoppers, Macrosteles fascifrons
      (Stal). The presence of virus in the tissues was determined by injecting their
      extracts into virus-free leafhoppers, then testing the latter singly for
      inoculativity on aster (Callistephus chinensis Nees.) seedlings. The virus was
      first recovered from the alimentary canal immediately after a 3-day acquisition
      access period and from the hemolymph and salivary glands on day 6 after the start
      of acquisition. The virus concentration, as indicated by the percentage of
      injected insects that became inoculative, increased rapidly in the alimentary
      canal, reached a peak by day 9, but then declined sharply by day 23 and remained
      at the same low level up to day 30, the longest time tested. The virus
      concentration in the hemolymph also increased rapidly, reached a peak by day 12,
      but remained at the same high level up to day 30. In the salivary glands the
      virus concentration increased gradually, and reached a high level by day 30. The
      increase of virus concentration in salivary glands was correlated with the
      increase in transmission by the source leafhoppers. The results suggest that the
      alimentary canal of the leafhopper is the initial site of virus multiplication,
      that hemocytes may be the main sites of virus multiplication, and that AYV must
      reach a certain concentration in the salivary glands before an insect can become
      inoculative.

PMID- 18614091
TI  - Poxvirus-induced acid deoxyribonuclease: regulation of synthesis; control of
      activity in vivo; purification and properties of the enzyme.
AB  - Of three nucleases induced by poxvirus, one is a nuclease that acts on denatured
      DNA at acid pH values. This enzyme has been purified over 3000-fold and has the
      following characteristics: It degrades heat-denatured DNA exonucleolytically but
      has negligible activity toward native DNA or RNA; the degradation of denatured
      DNA is not inhibited by native DNA but is competitively inhibited by sRNA; there
      is no requirement for added divalent cations; the pH optimum for the degradation
      of denatured DNA is 4.5, a pH at which the enzyme is insoluble; the enzyme has a
      K(m) of 7.7 x 10(-6) g and an S(20(o)w) of 5.8 +/- 0.3. There is no detectable
      enzyme activity with all of these characteristics in uninfected cells. In
      contrast to the other poxvirus-induced nucleases, the acid nuclease is
      synthesized under the direction of only progeny DNA templates. During the course
      of viral infection the enzyme undergoes a sharp transition, in vivo, from a
      soluble to bound state but is synthesized continuously for about 18 hours
      postinfection.

PMID- 18614092
TI  - Studies on the structural proteins of vaccinia virus. I. Structural proteins of
      virions and cores.
AB  - Radioactively labeled vaccinia virions grown in L cells were dissociated to yield
      the constituent polypeptide chains, which were then subjected to electrophoresis
      in polyacrylamide gels. Mechanical fractionation of these gels yielded complex
      profiles in which at least 17 components, some major, some minor, could be
      reproducibly identified. The relative mass in each component has been calculated
      from the amount of radioactivity incorporated. The principal component (VSP-4)
      accounts for about 28% of the total viral protein mass. Cores derived from
      virions by chemical treatment contain the principal viral protein component,
      which is clearly multiple, as well as two minor ones (VSP-1 and VSP-2), which are
      probably single polypeptide species. These latter two components are the two
      slowest moving ones, and therefore most probably have the largest molecular
      weights. Treatment of virions with the nonionic detergent NP 40 liberates one
      major viral protein component (VSP-6). This component accounts for 18.7% of viral
      protein, the second highest amount, and is also multiple in nature.

PMID- 18614093
TI  - Studies on the structural proteins of vaccinia virus. II. Kinetics of the
      synthesis of individual groups of structural proteins.
AB  - The time course of the synthesis of certain structural vaccinia virus proteins in
      mouse L fibroblasts was determined by pulse-labeling infected cells at intervals
      throughout the multiplication cycle and determining the degree of labeling of
      individual proteins of progeny virus after polyacrylamide gel electrophoresis.
      Overall viral structural protein synthesis reaches a peak in these cells at
      between 6 and 8 hours after infection, but then continues at a relatively high
      rate throughout the infection cycle. Different groups of viral structural
      proteins exhibit different patterns of synthesis. The synthesis of two proteins
      which are constituents of viral cores commences very early, as does that of a
      protein which is situated near the surface of the virion. These proteins are also
      synthesized in the presence of cytosine arabinoside, when viral DNA replication
      is inhibited, and are thus "early" proteins. The synthesis of the two early core
      proteins, but not that of the surface protein, appears to be subject to switch
      off; however, switch-off is not absolute, and small amounts of these proteins
      continue to be synthesized throughout the infection cycle. The presence of
      structural viral proteins in "soluble" cell extracts (supernatant solutions after
      centrifuging at 20,000 g for 60 minutes) was also examined. The structural viral
      protein complement of such cell extracts bears only limited resemblance to that
      of virions. Some structural viral proteins appear to be synthesized in the form
      of polypeptide chains larger than those actually incorporated into virions; other
      viral proteins appear to aggregate rapidly after their synthesis. This is true
      particularly of those structural proteins which are the latest to be synthesized.
      The implications of these results are discussed.

PMID- 18614094
TI  - Detection of defective (T-antigen inducing, but noninfectious) particles in
      preparations of SV40 virus.

PMID- 18614095
TI  - Oncogenic and transforming activity of hydroxylamine-inactivated SV40 virus.

PMID- 18614096
TI  - Suppression of the heat-sensitive mutants of the coliphage lambda.

PMID- 18614097
TI  - Effect of temperature on prophage attachment and detachment during heteroimmune
      superinfection.

PMID- 18614098
TI  - Interferon resistance of SV40 induced DNA synthesis.

PMID- 18614099
TI  - Hybridization of avian myeloblastosis virus RNA with DNA from chick embryo cells.

PMID- 18614100
TI  - Ribonuclease-induced stabilization of an alkali-labile TMV strain and lack of
      stabilization of reaggregated TMV protein.

PMID- 18614101
TI  - In situ alkaline degradation of turnip yellow mosaic virus RNA: a comparative
      analysis.

PMID- 18614102
TI  - Antigen-forming defective viruses of simian virus 40.
AB  - The presence of two kinds of defective virus particles was demonstrated in SV40
      preparations obtained by serial undiluted passage in African green monkey kidney
      (GMK) cell cultures. They were designated T and V particles, respectively. The
      former produces only T antigen and the latter V antigen in the nuclei of GMK
      cells, without producing infectious progeny. A tentative method of the titration
      of each particle is presented. The purified virion preparation obtained by the
      third undiluted passage was shown to consist mainly of physically heterogeneous
      defective particles. The average buoyant density of defective virions was
      significantly lower than that of plaque-forming particles. T particles were
      present in the light virion population.

PMID- 18614103
TI  - Totally asymmetric transcription of coliphage T7 in vivo: correlation with poly G
      binding sites.
AB  - In vivo transcription of T7 phage was studied by means of hybridization between
      phage-specific radioactive RNA and separated complementary strands of T7 DNA. The
      latter were preparatively separated by CsCl density-gradient centrifugation in
      the presence of guanine(G)-rich polyribonucleotides, which bind to one strand
      only. The separated strands failed to renature when annealed separately but
      renatured when mixed together. Pulse-labeled 3H-RNA, isolated from cultures of
      Escherichia coli B at various times after T7 infection, hybridized exclusively
      with the poly G-binding strand H, indicating that only this strand is transcribed
      in vivo. Non-poly G-binding strand L did not hybridize (less than 0.02%) with the
      in vivo synthesized T7 RNA, but both the H and L strands hybridized with
      enzymatically prepared 3H-RNA transcribed from denatured T7 DNA template. The
      fact that the poly G-binding, deoxycytidylate (dC)-rich clusters are restricted
      to the in vivo transcribing H strand, together with the absence of thymine-rich
      clusters in T7 DNA, is compatible with the hypothesis (Szybalski et al., 1966)
      that pyrimidine-rich clusters are related to RNA transcription, possibly as the
      initiation and termination sites.

PMID- 18614104
TI  - Studies on some strains of tobacco mosaic virus in orchids. I. Biological,
      chemical, and serological studies.
AB  - Seven isolates (01-07) of tobacco mosaic virus (TMV) were obtained from
      commercial orchids. These isolates comprise at least five distinct strains of TMV
      (01, 02, 04, 05, and 06). Of the five strains, four (01, 04, 05, and 06) are
      serologically indistinguishable from common TMV, but are distinct from each other
      and from other TMV strains when symptoms in various tobaccos and amino acid
      analyses are compared. The orchid strains of TMV differ from common TMV either by
      only a few amino acid exchanges, or by numerous amino acid exchanges. Strains 01
      and 04 possess a pair of exchanges represented by Ile, Val --> Ala, Thr. If these
      strains are assumed to have arisen from type TMV by spontaneous mutational
      events, then the observed results suggest that the mutations arose through
      amination of uracil to cytosine. Strain 06 differs from common TMV by three
      exchanges, two of which include histidine and methionine residues; both of these
      amino acids are absent in common TMV. Unlike most orchid TMV strains, strain 02
      (isolates 02 and 07) infects few tobaccos and differs from TMV by some 15 amino
      acid exchanges. It shares antigenic determinants, which are absent in common TMV,
      with HR and U2 strains of TMV.

PMID- 18614105
TI  - Serological studies on bromegrass mosaic virus and its protein fragments.
AB  - The serological properties of the capsids and dissociated protein subunits of
      bromegrass mosaic virus have been compared by immunodiffusion tests. Methods were
      developed to obtain non-mutually contaminated protein and virus preparations as
      well as the corresponding antisera. The breakdown of the capsids and the
      reaggregation of the subunits inside the agar gel during immunodiffusion tests
      was prevented by controlling the ionic environment inside the gel and by treating
      the antigens with formalin. The existence of antigenic determinants specific for
      only the capsid surface as well as that of determinants specific for only the
      dissociated subunit surface was demonstrated by intragel cross-absorption tests.

PMID- 18614106
TI  - Studies on complement-potentiated neutralizing antibodies (C'-PNAb) induced in
      rabbits inoculated with japanese encephalitis virus (JEV). I. The nature of C'
      PNAb.
AB  - The C'-PNAb induced by JEV grown in porcine kidney stable (PS) cells [JEV(PS)]
      inactivate not only the corresponding virus, hut also Western equine encephalitis
      (WEE), Eastern equine encephalitis (EEE), vesicular stomatitis (VS) and Sindbis
      viruses grown in PS cells or primary hamster kidney (HK) cell cultures in the
      presence of complement. The degree of complement-potentiated neutralizing (C'-PN)
      ability varies for each virus. The C'-PNAb do not, inactivate these viruses grown
      in mouse brain, even JEV. The C'-PN activity against viruses other than JEV(PS)
      is completely removed by absorption with the microsomal fraction of PS or HK
      cells, but not of mouse brain. The antibodies in fraction IgM induced by the
      microsomal fraction of PS or HK cells inactivate the viruses grown in PS cells to
      a different degree in the presence of complement, but not viruses grown in mouse
      brain. The activity of C'-PNAb against JEV(PS) is reduced to 2% of the original
      activity by absorption with sheep red cells. After absorption, the remaining C'
      PNAb are not further reduced by absorption with the microsomal fraction of PS
      cells, nor do they inactivate the other viruses grown on PS cells. The early
      rabbit hemagglutination-inhibition (HI) antibodies in fraction IgM induced by
      JEV(PS) could not only inhibit hemagglutination with JE, WEE, EEE, and Sindbis
      viruses grown on PS cells in the absence of complement, but could also facilitate
      HI in the presence of complement. However, they could not inhibit
      hemagglutination with these viruses grown in mouse brain, in the presence or
      absence of complement. This activity of HI could also be removed by absorption
      with the microsomal fraction of PS cells. These findings suggest that C'-PNAb are
      induced by host cell components associated with the virus, and that the early HI
      antibodies in fraction IgM are the same entities as C'-PNAb.

PMID- 18614107
TI  - Specific chromosome aberrations in cells persistently infected with type 2
      hemadsorption virus.
AB  - A clonal strain derived from HeLa-S3 cells persistently infected with
      hemadsorption type 2 virus (S3/HA2) has general properties comparable to those
      previously described for persistently infected wild-type HeLa cells (HeLa/HA2)
      except that partial cytopathic changes were observed in the process of
      establishing persistent infection in S3 cells. A chromosomal analysis was
      conducted on S3/HA2 cells and S3 cells freshly infected with the virus. The modal
      number of chromosomes in S3 HA2 cells and freshly infected S3 cells was shown to
      be 68, hypotriploidy as also observed in control S3 cells. The karyotypic
      changes, however, occurred in virtually 100% of cells. The chromosomal changes
      are characterized by the deletion of one of the chromosome 22 and the supposed X
      chromosome and the addition of each one chromosome to the chromosome 19 and 20.
      Karyotypic change as observed in S3/HA2 cells was obtained in S3 cells as early
      as 24 hours after infection. It was suggested that these changes are not due to
      the selection of particular cells present in the uninfected S3 culture hut to the
      virus infection itself.

PMID- 18614108
TI  - Serological behavior of cucumber mosaic virus (strain Y) and the virus protein.
AB  - Antisera with titers of 1/128 were obtained by injecting rabbits intravenously
      (iv) or intramuscularly (im) with purified cucumber mosaic virus (strain Y) (CMV
      Y). Gel-diffusion tests with CMV-Y resulted in the formation of a curved band
      with the iv antisera and both a curved and a straight band with the im antisera.
      The curved band results from the combination of high molecular weight virus
      antigen with specific antibody, and the straight band originates from the
      combination of a product of virus degradation and its specific antibody. Crude
      sap from infected tobacco and protein obtained from CMV-Y by KCl degradation did
      not react with iv antiserum in gel-diffusion tests and formed only the straight
      band with im antiserum. Both CMV-Y and virus protein precipitated with im
      antiserum in tube precipitin tests, but no precipitation occurred when iv
      antiserum was tested with virus protein. However, virus protein possesses the
      antigenic determinants of CMV-Y, as shown by cross absorption in test tubes. The
      ability of the protein to bind antibodies specific for the curved band antigenic
      determinant of CMV-Y is reduced when the protein is precipitated by dialysis
      against water or used in intragel absorption tests, but its ability to bind
      straight band antibody is not affected. Exposure of CMV-Y to 37 degrees for 1
      hour or to buffers other than 0.005 M borate, pH 9.0, such as 0.05 M borate, pH
      9.0, and 0.05 M phosphate, pH 8.0, resulted in reduction of the major virus peak
      and the appearance of smaller nucleoprotein fragments (shown by density gradient
      centrifugation).

PMID- 18614109
TI  - The Luria-Latarjet effect studied by T4-lysozyme production.
AB  - The replication of bacteriophage T4 in Escherichia coli is sensitive to
      ultraviolet light (UV). The classical plaque assay shows a considerable increase
      in UV resistance starting at about 5 minutes after the bacteria are infected.
      Production of phage lysozyme starts about 10 minutes after infection and is
      sensitive to irradiation. Its UV resistance increases at about 4 minutes. The
      appearance of resistance, measured by both the plaque assay and lysozyme
      production, is inhibited by p-fluorophenylalanine. Resistance appears at the
      normal time in bacteria infected by a mutant phage amN116 whose major DNA
      synthesis is delayed beyond 20 minutes. These results suggest that the same event
      is responsible for resistance of both plaque formation and lysozyme production.
      The principal advantage of the lysozyme assay is that resistance can be detected
      more directly than with the plaque assay. Bacteria irradiated 7 minutes after
      infection were resistant when tested at 11 minutes. Resistance mechanisms that
      depend on gradual recovery after plating are ruled out by these results. So are
      mechanisms that require extensive DNA synthesis. The results are consistent with
      an event that takes place 5 minutes after infection and requires protein
      synthesis and at most a small quantity of DNA synthesis. They are in accord with
      a highly UV-sensitive switch from early to late functions being the principal
      initial target.

PMID- 18614110
TI  - Excision of lambda prophage: effects on host survival.
AB  - Induction with ultraviolet light of K12 lysogens carrying defective prophages
      leads to death of the host cell. In order to determine whether the killing
      accompanying induction was due to diffusible phage products, or was a result of
      prophage excision itself, the survival of lysogens carrying DNA defective
      prophages on an extra chromosomal site (the F-gal episome), were examined.
      Induction of prophages, carrying mutations in the x region, or the N, O or P
      cistrons, from this location, did not result in host death, but, with the
      exception of mutants in the x region of the lambda chromosome, it did result in
      loss of the episome. On the basis of these results, it is proposed that the
      lethal event in induction of the DNA-defective mutants is due to prophage
      excision, which leads to interruption of the host chromosome, and cell death.

PMID- 18614111
TI  - Excision of the lambda prophage: effects on linkage relationships of Escherichia
      coli chromosome.
AB  - As a result of earlier work with K12 lysogens carrying defective prophages, it
      was proposed that the lethal event in induction was due to interruption of the
      host chromosome and that the different levels of survival after induction with
      ultraviolet light of DNA defective mutants, in the x region, and the N, O, and P
      cistrons, was due to different extents of repair. To test this model, the effects
      of zygotic induction on the linkage between two bacterial markers, gal and bio,
      on either side of the lambda prophage, was examined. This linkage was destroyed
      after zygotic induction of mutants in the N cistron. Zygotic induction of mutants
      in cistron O resulted in a 5-fold depression of the linkage, while induction of
      mutants in cistron P and in the x region resulted in complete restoration of the
      linkage. The results are discussed in relation to the model of excision, and
      possible different extents of repair.

PMID- 18614112
TI  - Host survival following infection with or induction of bacteriophage lambda
      mutants.
AB  - The lethal effects of lambda infection and lambda induction were studied using
      conditional lethal mutants of phage lambda in the su- host W3350. Phage with
      mutations in Q and R, which are blocked after DNA replication, kill promptly and
      efficiently on induction or infection. Infection with mutants defective in O and
      P, which do not replicate, kills less efficiently, although these mutants do kill
      effectively at high multiplicity of infection. Heat induction of lysogens
      carrying DNA defective mutants O or P promptly arrests host DNA synthesis, but
      this leads to killing only after a considerable lag. Heating also blocks transfer
      of an F-gal episome by a lysogen in which a temperature inducible O or P mutant
      is carried on the episome. These effects of heating are reversed by cooling,
      which leads to recovery of host DNA synthesis and recovery of the ability to
      transfer the episome. The effects of heating lysogens for temperature inducible
      DNA defective phage are interpreted to result from interruption of the
      Escherichia coli chromosome (or episome), which in itself, is not lethal to the
      host. Their reversal on cooling is attributed to repair of the break in the
      chromosome, which permits survival, often associated with curing. Evidence is
      presented that interruption of the E. coli chromosome can also be produced by
      infection, but the relationship of this event to loss of viability on infection
      is still uncertain. N mutants kill even less efficiently than O and P mutants on
      infection and show killing and DNA arrest on thermal induction only after an
      initial stimulation of DNA synthesis. They neither cure appreciably, nor resume
      DNA synthesis on cooling, once DNA synthesis is arrested. Not all the properties
      of N mutants can presently be explained.

PMID- 18614113
TI  - Integration of lambda b2 in Escherichia coli K12-B hybrid.
AB  - The gal-bio region was transduced from Escherichia coli B to K12 and lysogenized
      with lambda b2. By means of P1 transduction mapping, the lambda b2 prophage was
      shown to be inserted between gal and bio and to be circularly permuted in the
      same way as lambda b2+ in K12. Increased frequency of recombinations within the
      prophage was observed when the viral genes were mapped with respect to bio
      instead of to gal. The results are interpreted to indicate the existence of a
      region in lambda situated close to the b2 region and homologous with a lambda
      attachment site of E. coli B but not with that of E. coli K12.

PMID- 18614114
TI  - Shope fibroma virus assay based on enumeration of cells containing inclusion
      bodies.
AB  - Inclusion bodies stainable by the May-Grunwald-Giemsa and fluorescent, antibody
      techniques are seen after infection of HeLa, human amnion, and rabbit kidney
      cells with Shope fibroma virus. At 20 hours after infection the number of
      inclusion bodies is linearly related to the dilution of virus and the volume of
      inoculum. These observations provide the basis for an assay. The inclusion-body
      count is fast, reproducible, and more sensitive than the plaque assay. There is a
      quantitative relationship between the amount of virus neutralized, measured by
      the inclusion-body count, and the dilution of added antibody.

PMID- 18614115
TI  - Studies on neutralization of Japanese encephalitis virus (JEV). I. Further
      neutralization of the resistant virus fraction by an interaction between
      antivirus IgG antibody and IgG heterotype or allotype antibody.
AB  - When JE viruses interact with anti-JEV mouse IgG antibody (anti-JEV antibody), a
      resistant virus fraction remains which is not neutralized further by the
      antibody. This resistant virus fraction was neutralized by anti-mouse IgG rabbit
      IgG antibody (heterotype antibody) or anti-mouse IgG mouse IgG antibody (allotype
      antibody). The kinetics of this secondary neutralization was of the first order,
      as was that of the first neutralization by anti-JEV antibody. The rate of the
      secondary neutralization was proportional to the concentration of the heterotype
      or allotype antibody. The first neutralization could be reversed in part by
      dilution, and the susceptibility of the resistant virus fraction to anti-JEV
      antibody was increased upon dilution. On the contrary, the susceptibility of the
      resistant virus fraction to the heterotype or allotype antibody decreased with
      dilution. These findings suggested that the secondary neutralization of the
      resistant virus fraction was resulted in the interaction between reversibly
      combined anti-JEV antibody and the heterotype or allotype antibody.

PMID- 18614116
TI  - Electron microscopic characterization of duck plague virus.
AB  - A virus [duck plague Long Island virulent virus (DPLIVV)] was isolated from ducks
      in a recent disease outbreak on farms on Long Island, New York. This disease
      exhibited characteristics similar to duck plague, a disease in ducks endemic to
      the Netherlands and India and not previously reported in the United States. An
      attenuated strain of the duck plague virus from the Netherlands was studied
      morphologically by electron microscopy. Its infectivity for duck embryo cell
      cultures was also studied. The DPLIVV and the Holland strain were morphologically
      identical. Furthermore, enzymatic digestion of methacrylate-embedded thin
      sections of mature virus particles showed that both Holland duck plague
      attenuated virus and DPLIVV contained deoxyribonucleic acid. The dimensions of
      the mature cytoplasmic particle; nucleocapsid diameter ca. 75 micron, envelope
      diameter ca. 181 micron, and other characteristics would presumably place duck
      plague virus in the herpesvirus group.

PMID- 18614118
TI  - Tobacco leaf veins as sources of a cucumber mosaic virus for aphids.

PMID- 18614117
TI  - Enhancement of tobacco rattle virus stable form infection by heterologous short
      particles.

PMID- 18614119
TI  - The serological relationship between tobacco mosaic virus and cucumber viruses 3
      and 4.

PMID- 18614120
TI  - Fine structure of new Bacillus subtilis phage AR9 with complex morphology.

PMID- 18614121
TI  - Blue light promotes symptom formation and virus multiplication in plants.

PMID- 18614122
TI  - Enhancement of infectivity of a mammalian virus preparation after injection into
      insects.

PMID- 18614123
TI  - The effect of 5-iodo-2'-deoxyuridine 5'-triphosphate, an allosteric inhibitor, on
      deoxycytidylate deaminase "induced" by herpes simplex virus.

PMID- 18614124
TI  - "Mathematical models" for infectivity dilution curves of plant viruses.

PMID- 18614125
TI  - Viruslike particles in adult Drosophila melanogaster.

PMID- 18614126
TI  - Immature forms of vaccinia virus: morphological observations from thin sections
      of infected human skin.

PMID- 18614127
TI  - Immunochemical studies of foot-and-mouth disease. III. Acridine orange staining
      of agar gel precipitin reactions.
AB  - Agar gel diffusion precipitin reactions obtained with foot-and-mouth disease
      virus antigens were examined by an acridine orange staining procedure. After
      treatment with 0.01% acridine orange, precipitin bands produced by the virus
      particles (140 S antigen) fluoresced flame red when examined under ultraviolet
      light and with 0.001% to 0.0001% acridine orange, a yellow green. Treatment with
      RNase prior to staining inhibited the reaction, whereas, treatment with DNase did
      not. This was in accord with the known RNA nature of foot-and-mouth disease
      virus. Precipitin bands formed by the 75 S, 12 S, and infection-associated (VIA)
      antigenic components did not take up acridine orange, an indication that they do
      not contain detectable amounts of nucleic acid.

PMID- 18614128
TI  - Suppressor-sensitive mutants of coliphage phi80.
AB  - About fifty suppressor sensitive (sus) mutants of phage phi80 were isolated after
      hydroxylamine treatment, and these were classified into fourteen cistrons. In
      vitro and in vivo complementation experiments revealed that at least five
      cistrons were concerned with head formation and that at least six cistrons were
      concerned with tail formation in phi80. Some presumed "early" mutants were also
      found. Defective lysogens were isolated from a phi80-lysogenic nonpermissive
      strain using the colicin plate method (Gratia, 1966). In these strains deletions
      which affected the colicin B receptor gene extended for varying distances into
      prophage phi80. Marker rescue experiments were carried out with these deletion
      lysogens by infecting various sus mutants, and the gene order in prophage phi80
      was determined. Clustering of all head genes and also of tail genes, as in phage
      lambda, were demonstrated by the results of the prophage deletion mapping as well
      as the two-factor crosses performed among the sus mutants. Moreover, the gross
      gene arrangement of phi80 was also similar to that of phage lambda: namely, the
      cluster of head genes was found to be located at one end of the vegetative map of
      phi80, being followed by that of tail genes, and presumed "early" genes are
      located at the other end of the map.

PMID- 18614129
TI  - Production of single-strand breaks in covalent circular lambda phage DNA in
      superinfected lysogens by monoalkylating agents and the joining of broken DNA
      strands.
AB  - Fast sedimenting, double-stranded, covalent circular lambda phage DNA in
      superinfected lysogens of Escherichia coli is converted to notched circular DNA,
      sedimenting slowly in alkaline sucrose gradients, by methylmethane sulfonate
      (MMS) treatment during incubation at 37 degrees . During further incubation after
      removal of the MMS, the slow sedimenting DNA reverts to the fast sedimenting
      structure. Covalent circular DNA, phenol extracted from superinfected lysogens
      and exposed to MMS, ethylmethane sulfonate, or 2-chloroethyl ethyl sulfide
      requires the presence of a heat-labile factor from extracts of E. coli for the
      breaks to appear. The cleavage of alkylated covalent circular DNA in vivo and the
      subsequent rejoining of the broken DNA strands to produce reconstructed covalent
      circular DNA may reflect the action of an excision-like repair process which is
      under different genetic control from that of pyrimidine dimer excision.

PMID- 18614130
TI  - On the generality of the contingent orienting hypothesis.
AB  - The contingent-orienting hypothesis states that attentional capture by a task
      irrelevant stimulus is contingent on whether that stimulus shares a feature
      property that is critical to the task at hand [Folk, C. L., Remington, R. W., &
      Johnston, J. C. (1992). Involuntary covert orienting is contingent on attentional
      control settings. Journal of Experimental Psychology: Human Perception and
      Performance, 18, 1030-1044]. Studies supporting this hypothesis have mostly used
      set size four displays throughout the experiment and thus constrict its
      ecological validity, since conclusions drawn from experiments using fixed set
      size displays may not be generalized to other conditions with different set
      sizes. We used a spatial cueing paradigm in which a non-informative onset or
      color cue preceded an onset or a color target, and manipulated set size as a
      within- or between-subject factor. In four experiments, the original finding of
      Folk et al. (1992) was replicated only when a fixed set size (four) was used
      throughout. When both set-size four and eight were used in an experiment,
      stimulus-driven capture by onset in search of a color target was found even for
      set-size four displays. These results raise doubts as to the generality of the
      contingent-orienting hypothesis and help to delineate the boundary conditions on
      this hypothesis.

PMID- 18614131
TI  - Acquisition of vernal and atopic keratoconjunctivitis after bone marrow
      transplantation.
AB  - PURPOSE: Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC)
      result from genetic and environmental factors. We present patients who had no
      history of atopic disorders before bone marrow transplantation (BMT) and who seem
      to have acquired VKC or AKC from their donors, who had atopic disorders. DESIGN:
      Observational case series. METHODS: The patients in this study were part of a
      cohort of patients who had undergone allogeneic hemapoietic stem cell
      transplantation (HSCT) from January 1997 through December 2007. Of 621 HSCT
      recipients, four recipients who were free of allergic disorders acquired VKC or
      AKC from their afflicted donors after HSCT. Each patient underwent complete
      ophthalmologic examination, determination of the total serum immunoglobulin (Ig)
      E, and conjunctival scrapings. RESULTS: Four (0.64%) of 621 patients who had
      undergone HSCT acquired VKC or AKC after BMT. The donors had VKC or atopic
      dermatitis. In addition, in two of these four patients, asthma developed. One
      patient had elevated total serum IgE. Conjunctival scrapings of all four patients
      revealed the presence of eosinophils. One patient had concurrent graft-versus
      host disease. CONCLUSIONS: VKC and AKC are systemic allergic disorders
      characterized by local ocular manifestations. This report suggests the
      possibility of the acquisition of VKC or AKC after BMT by adoptive transfer.

PMID- 18614132
TI  - Risk factors for scleral buckle removal: a matched, case-control study.
AB  - PURPOSE: To identify preoperative, perioperative, and postoperative risk factors
      for scleral buckle (SB) removal. DESIGN: Retrospective, consecutive, matched,
      case-control study. METHODS: Cases included all patients undergoing SB removal
      between August 1988 and December 2007 at a single academic center. Cases were
      matched against four randomly selected control patients who underwent SB
      implantation during the same year as the case. Odds ratios (OR) were calculated
      for each factor investigated. RESULTS: Forty cases of SB removal and 148 matched
      control cases were identified. Three cases of SB removal were omitted from
      analysis because of incomplete records. Factors associated with SB removal for
      any reason, using univariate analysis, included concurrent globe-penetrating
      injury at time of SB placement (OR, 24; 95% confidence interval [CI], 2.9 to
      200), concurrent pars plana vitrectomy (PPV) (OR, 17.3; 95% CI, 4.9 to 61),
      diabetes mellitus (DM) (OR, 7.3; 95% CI, 1.8 to 30), prior chronic topical ocular
      therapy (OR, 4.3; 95% CI, 1.7 to 11), and subsequent ocular procedures (OR, 3.4;
      95% CI, 1.5 to 7.5). Factors independently associated with SB removal using
      multivariate analysis included concurrent globe-penetrating injury (OR, 27.3; 95%
      CI, 1.7 to 426), concurrent PPV (OR, 11.3; 95% CI, 2.9 to 45), DM (OR, 8.9; 95%
      CI, 1.3 to 58), and subsequent ocular procedures (OR, 3.9; 95% CI, 1.4 to 11).
      Factors that did not alter SB removal risk included patient age; gender; and
      type, size, or location of buckling elements used. CONCLUSIONS: Awareness of
      these risk factors may be valuable for the surgical planning of retinal
      detachment repair in patients at higher risk for subsequent SB removal and for
      risk stratification subsequent to SB implantation.

PMID- 18614133
TI  - Two-year results of photodynamic therapy for polypoidal choroidal vasculopathy.
AB  - PURPOSE: To report on the two-year visual outcomes of indocyanine green
      angiography-guided photodynamic therapy (PDT) for polypoidal choroidal
      vasculopathy (PCV) patients. DESIGN: Retrospective case study. METHODS: A
      retrospective analysis that examined the clinical and angiographic data related
      to 41 eyes of 38 PCV patients (25 males, 13 females; average age +/- standard
      deviation [SD], 72.9 +/- 7.4 years) with follow-up periods of 24 months or more.
      RESULTS: The average number of PDT treatments was 1.65. After the 12-month follow
      up, 12 eyes required retreatment. Although the mean visual acuity (VA) +/- SD
      before PDT (0.55 +/- 0.38 logarithm of the minimum angle of resolution units)
      improved to 0.46 +/- 0.41 at 12 months after the initial PDT, at 24 months, it
      declined significantly to 0.59 +/- 0.44 (P = .0018). Although only seven of 41
      eyes exhibited VA deterioration at the 12-month follow-up examination, a
      decreased VA was noted in 18 eyes during the period starting from the 12-month
      follow-up until the final examination. The cases were bilateral in 11 (61.1%) of
      the 18 eyes. At the final examination, the mean VA of the bilateral cases but not
      the unilateral cases was significantly lower than that observed for the initial
      VA. CONCLUSIONS: PDT is an effective treatment against PCV over the short-term
      for both unilateral and bilateral cases. However, the VA prognosis may not the
      same after 12 months, especially for those PCV patients who have exudative age
      related macular degeneration in contralateral eye.

PMID- 18614134
TI  - Effects of aging on corneal biomechanical properties and their impact on 24-hour
      measurement of intraocular pressure.
AB  - PURPOSE: To study the effects of aging on corneal biomechanical properties and
      their impact on 24-hour measurement of intraocular pressure (IOP). DESIGN:
      Experimental study. METHODS: Fifteen older volunteers with healthy eyes (age
      range, 50 to 80 years) were housed for one day in a sleep laboratory with a 16
      hour diurnal or wake period and an eight-hour nocturnal or sleep period. Every
      two hours, sitting corneal hysteresis, corneal resistance factor, and IOP were
      measured. Central corneal thickness (CCT) was measured using an ultrasound
      pachymeter. Data were compared with previous observations in 15 healthy younger
      volunteers (age range, 20 to 25 years). RESULTS: Variations in 24-hour corneal
      hysteresis and corneal resistance factor were not significant in the older
      subjects, but there were time-dependent variations in CCT and IOP. The nocturnal
      CCT was thicker than the diurnal CCT, but the IOP difference between the diurnal
      and nocturnal periods was not significant. Cosine-fits of CCT and IOP showed
      synchronized 24-hour rhythms. The phase timing of CCT rhythm appeared
      significantly earlier than the phase timing of IOP rhythm. Compared with younger
      subjects, older subjects had a lower mean 24-hour corneal hysteresis and corneal
      resistance factor, but not a lower CCT. Phase timings of 24-hour rhythms of CCT
      and IOP were significantly delayed by aging. CONCLUSIONS: Aging may lower corneal
      hysteresis and corneal resistance factor, but neither parameter shows a
      significant 24-hour variation. Aging may not change CCT significantly, but can
      shift its 24-hour rhythm. The 24-hour IOP pattern in this group of older subjects
      is not an artifact resulting from a variation in corneal hysteresis, corneal
      resistance factor, or CCT.

PMID- 18614135
TI  - Metallic intraocular foreign bodies: characteristics, interventions, and
      prognostic factors for visual outcome and globe survival.
AB  - PURPOSE: To describe metallic intraocular foreign body (IOFB) injuries and
      identify prognostic factors for visual outcome and globe survival. DESIGN:
      Interventional, consecutive, retrospective case series. METHODS: setting: Wills
      Eye Hospital. study population: Ninety-six eyes of 96 patients with metallic
      intraocular foreign bodies. procedures: Metallic IOFB injuries between January
      1991 to June 2002 were reviewed for clinical characteristics, surgical
      intervention, and outcome. Univariate and multivariate analyses were performed to
      identify prognostic variables. main outcome measures: Final visual acuity and
      globe survival. RESULTS: The average patient age was 33.0 years with a male
      predominance (94%). Forty percent of eyes had a presenting vision of 20/50 or
      better. Following IOFB removal, 40% of patients required additional
      interventions. Thirty-one percent of eyes had a final acuity of 20/50 or better.
      Eight percent of patients ultimately required enucleation or evisceration.
      Excellent visual outcome (defined as > or =20/50) was associated with multiple
      variables, including normal lens at presentation and anterior segment IOFB (P<
      .003). Factors associated with poor visual outcome (defined as <20/200) included
      uveal prolapse and posterior segment IOFB (P < .0003). Globe loss was associated
      with younger age, presenting light perception (LP) or no light perception (NLP)
      vision, BB/pellet injury, and the presence of an afferent pupillary defect (P <
      .01). CONCLUSIONS: Multiple prognostic factors were identified in this large
      analysis of metallic IOFB injuries, which may help predict visual outcome and
      globe survival. Most of these variables were independent of intervention and can
      be identified at the time of initial presentation.

PMID- 18614136
TI  - Comparison of visual results between laser-assisted subepithelial keratectomy and
      epipolis laser in situ keratomileusis to correct myopia and myopic astigmatism.
AB  - PURPOSE: To compare the visual results after laser-assisted subepithelial
      keratectomy (LASEK) and epipolis laser in situ keratomileusis (epi-LASIK) to
      correct myopia. DESIGN: Retrospective, interventional, nonrandomized comparative
      study. METHODS: Patients treated with LASEK to correct myopia < or = -9.00
      diopters (D) were compared to age- and refraction-matched patients treated with
      epi-LASIK using the same excimer laser (Esiris; Schwind Eye Tech Solutions,
      Kleinostheim, Germany). The epithelial flap was replaced after the ablation in
      every case. The visual results after both procedures were compared at each
      postoperative visit (one day, one week, one and three months). RESULTS: Ninety
      four consecutive eyes were included in the study (47 in each group), matched for
      age and refraction. The preoperative spherical manifest refraction was -3.98 +/-
      2.40 D in the LASEK group and -3.95 +/- 2.40 D in the epi-LASIK group (P = .9)
      (range -0.50 to -9.00 D). The uncorrected visual acuity (UCVA) one day
      postoperatively was 0.7 +/- 0.2 and 0.5 +/- 0.2 (P < .001), and one week after
      surgery it was 0.8 +/- 0.2 and 0.7 +/- 0.2, respectively (P = .1). The difference
      was again statistically significant one month after surgery (0.94 +/- 0.1 after
      LASEK, 0.82 +/- 0.1 after epi-LASIK, P < .001), but not three months
      postoperatively (1.06 +/- 0.21 and 1.03 +/- 0.18, respectively, P = .1). UCVA was
      > or =1.0 in 78.7% of LASEK eyes and 65.9% of epi-LASIK eyes three months after
      surgery. At that moment, the safety indices were 0.99 +/- 0.1 after LASEK and
      0.93 +/- 0.1 after epi-LASIK (P = .04). The efficacy indices were 0.97 +/- 0.1
      and 0.89 +/- 0.1, respectively (P = .01). CONCLUSIONS: Our results suggest a
      faster visual rehabilitation and better safety and efficacy outcomes after LASEK
      compared to epi-LASIK with repositioning of the epithelial flap when correcting
      low to moderate myopia.

PMID- 18614137
TI  - Non-Descemet stripping automated endothelial keratoplasty for endothelial
      dysfunction secondary to argon laser iridotomy.
AB  - PURPOSE: To report clinical outcomes of non-Descemet stripping automated
      endothelial keratoplasty (nDSAEK) as treatment of endothelial dysfunction
      secondary to argon laser iridotomy (ALI). DESIGN: Single-center, prospective,
      noncomparative, interventional case series. METHODS: Six eyes of six patients
      (two men, four women; mean age, 74.5 years) with bullous keratopathies secondary
      to ALI were treated with endothelial keratoplasty without recipient Descemet
      stripping. The donor endothelial lamella was inserted using a pull-through
      technique using a Busin glide with intraocular lens glide (i.e., Kobayashi double
      glide technique). Best-corrected visual acuity (BCVA), astigmatism, and donor
      central endothelial cell density (ECD) were recorded before surgery and at six
      months after surgery. Intraoperative and postoperative complications also were
      recorded. Main outcome measures were preoperative and postoperative central ECD,
      with calculation of cell loss rate. BCVA, induced astigmatism, and complications
      also were evaluated. RESULTS: All patients reached more than 20/32 BCVA, with two
      (33.3%) reaching 20/20. Mean induced astigmatism in measurable cases was 0.85 +/-
      0.49 diopters. The average and standard deviation ECD at six months were 2390.5
      +/- 522.4 cells/mm(2) (range, 1589 to 2898 cells/mm(2)), representing a mean cell
      loss from preoperative donor cell measurements of 25.8% +/- 14.7%. Complications
      included one case of donor dislocation requiring rebubbling (16.7%) and one case
      of subclinical endothelial rejection (16.7%). CONCLUSIONS: This modified
      endothelial keratoplasty technique (nDSAEK and double-glide technique) for
      treatment of endothelial dysfunction secondary to ALI produced excellent clinical
      outcomes such as reduced endothelial cell loss, good visual acuity, and minimal
      induced astigmatism.

PMID- 18614138
TI  - Intramural duodenal diverticulum mimicking a periampullary neoplasm.
AB  - A 34-year-old woman presented with epigastric pain, nausea, and dyspepsia.
      Contrast-enhanced computerized tomography revealed a small mass in the duodenal
      wall mimicking a periampullary neoplasm and, at endoscopic examination, a
      periampullary submucosal tumor was suspected. The diagnosis of intramural
      duodenal diverticulum (IDD) was made by an x-ray barium meal that showed a finger
      like sac filled with barium, the so-called "windsock sign." IDD is a rare
      congenital abnormality caused by an anomalous process of recanalization of the
      primitive foregut. The intermittent filling and emptying of the IDD is
      responsible for epigastric pain, nausea, and vomiting. When IDD is symptomatic,
      surgical or endoscopic treatment is recommended.

PMID- 18614139
TI  - Relationship between emergency presentation, systemic inflammatory response, and
      cancer-specific survival in patients undergoing potentially curative surgery for
      colon cancer.
AB  - BACKGROUND: Emergency presentation is recognized to be associated with poorer
      cancer-specific survival following curative resection for colorectal cancer. The
      present study examined the hypothesis that an enhanced systemic inflammatory
      response, prior to surgery, might explain the impact of emergency presentation on
      survival. METHODS: In all, 188 patients undergoing potentially curative resection
      for colorectal cancer were studied. Of these, 55 (29%) presented as emergencies.
      The systemic inflammatory response was assessed using the Glasgow Prognostic
      Score (mGPS), which is the combination of an elevated C-reactive protein (>10
      mg/L) and hypoalbuminemia (<35 g/L). RESULTS: In the emergency group, tumor stage
      was greater (P < 0.01), more patients received adjuvant therapy (P < 0.01) more
      patients had an elevated mGPS (P < 0.01), and more patients died of their disease
      (P < 0.05). The minimum follow-up was 12 months; the median follow-up of the
      survivors was 48 months. Emergency presentation was associated with poorer 3-year
      cancer-specific survival in those patients aged 65 to 74 years (P < 0.01), in
      both males and females (P < 0.05), in the deprived (P < 0.01), in patients with
      tumor-node-metastasis (TNM) stage II disease (P < 0.01), in those who received no
      adjuvant therapy (P < 0.01), and in the mGPS 0 and 1 groups (P < 0.05) groups. On
      multivariate survival analysis of patients undergoing potentially curative
      surgery for TNM stage II colon cancer, emergency presentation (P < 0.05) and mGPS
      (P < 0.05) were independently associated with cancer-specific survival.
      CONCLUSIONS: These results suggest that emergency presentation and the presence
      of systemic inflammatory response prior to surgery are linked and account for
      poorer cancer-specific survival in patients undergoing potentially curative
      surgery for colon cancer. Both emergency presentation and an elevated mGPS should
      be taken into account when assessing the likely outcome of these patients.

PMID- 18614140
TI  - Intrahepatic Glissonian approach for laparoscopic right segmental liver
      resections.
AB  - BACKGROUND: Experience with laparoscopic procedures and recent advances in
      laparoscopic devices have created an evolving interest in the application of
      these techniques to liver resection. However, laparoscopic liver resection has
      not been widely developed and anatomical segmental liver resection is not
      currently performed due to difficulty to control segmental Glissonean pedicles
      laparoscopically. METHODS: Seven consecutive patients underwent laparoscopic
      liver resection using an intrahepatic Glissonian approach from April 2007 to
      September 2007. Three patients underwent laparoscopic bisegmentectomy 6-7 and 4
      patients underwent laparoscopic right hemihepatectomy. RESULTS: Blood transfusion
      was required in 1 patient. Mean operation time was 460 minutes (range 300-630
      minutes). The median hospital stay was 5 days (range 3-8 days). One patient
      developed bile leakage that was treated conservatively. No patient had
      postoperative signs of liver failure. No postoperative mortality was observed.
      CONCLUSIONS: The main advantage over other techniques is the possibility to gain
      a rapid and precise access to the right posterior and anterior sheaths
      facilitating right hemihepatectomy, and right anterior and posterior
      sectionectomies. We believe that the described technique facilitates laparoscopic
      liver resection by reducing the technical difficulties in pedicle control and may
      increase the development of segment-based laparoscopic liver resections.

PMID- 18614141
TI  - Are mastectomy rates a reasonable quality measure of breast cancer surgery?
AB  - BACKGROUND: Quality measures of breast cancer clinical management adopted by the
      National Quality Forum do not address the quality of surgical performance. We
      evaluated mastectomy rate as one potential quality indicator. METHODS: We
      reviewed the surgical management of small (stage T1; < or =2 cm) invasive breast
      tumors in patients treated from April 2003 through April 2007 at our institution.
      For patients undergoing mastectomy, factors leading to the selection of
      mastectomy were analyzed. RESULTS: We identified 496 patients with invasive
      breast cancer: 433 did not undergo neoadjuvant chemotherapy, and 319 of these had
      pathologic tumors < or =2 cm in size. Of these, 55 (17.2%) underwent initial
      mastectomy. Medical contraindications to breast conservation were identified in
      42 of 319 (13.2%) patients, whereas the selection of mastectomy was attributed to
      patient choice in 13 of 319 (4.1%) patients. CONCLUSIONS: Medical
      contraindications to breast-conserving therapy were much more common than patient
      choice as the indication for mastectomy. Institution- or surgeon-specific
      mastectomy rates are unlikely to reflect the complexity of decision making in the
      surgical management of patients with breast cancer.

PMID- 18614142
TI  - Competency assessment in simulation-based procedural education.
AB  - The field of simulation-based procedural education in medicine is undergoing
      rapid development, with significant improvements in both graphic and tactile
      fidelity. As a consequence, the use of simulation for competency assessment and
      credentialing is evolving rapidly. Establishing the conceptual framework for
      developing such assessments using simulation is becoming critical to the
      expansion of simulation-based education and assessment in medicine. Although
      medical literature explores the educational theories in other aspects of medical
      education, the applicability of those concepts to the simulation of time-critical
      and clinically dangerous procedures has not been addressed explicitly. In
      particular, the issue of how one establishes standards for simulation-based
      procedures is central to how simulation would be used for competency assessment.
      This article briefly reviews the current medical education theories and discusses
      their applicability to simulation-based education. An alternative methodology of
      standards setting involving the use of benchmarking may be more appropriate to
      assessing critical procedural skills. Although much of the existing simulation
      literature (and practice) implicitly uses benchmarking methods, the conceptual
      framework that justifies its use has not been discussed explicitly. Finally, the
      development of clinical benchmarks as the standards-setting mechanism for
      procedural simulation-based learning, feedback, and assessment will be critical
      to establishing the clinical relevance of simulation.

PMID- 18614143
TI  - A review of the management of gallstone disease and its complications in
      pregnancy.
AB  - BACKGROUND: Symptomatic gallstone disease is the second most common abdominal
      emergency in pregnant women. There have been significant developments in the
      management of gallstone disease, but risk to the fetus has prevented their
      routine application in pregnant women. We reviewed the literature to find the
      current best evidence for the management of gallstones and its complications in
      pregnancy. DATA SOURCES: MEDLINE and PubMed literature searches were performed to
      identify original studies. RESULTS AND CONCLUSIONS: Six studies comparing
      conservative with surgical management of cholecystitis showed no significant
      difference in incidence of preterm delivery (3.5% vs 6.0%, P = .33) or fetal
      mortality (2.2% vs 1.2%, P = .57). There was no maternal or fetal mortality in 20
      reports of laparoscopic cholecystectomy and 9 reports of endoscopic retrograde
      cholangiopancreatography, thus indicating their safety when performed with
      necessary precautions. Laparoscopic cholecystectomy is a safe procedure in all
      trimesters. In 12 reports of gallstone pancreatitis, fetal mortality was 8.0%
      versus 2.6% (P = .28) in conservative and surgical groups, respectively,
      suggesting the need for earlier surgical intervention.

PMID- 18614144
TI  - Laparoscopic versus open repair of incisional/ventral hernia: a meta-analysis.
AB  - BACKGROUND: The aim of this article is to analyze laparoscopic versus open repair
      of incisional/ventral hernia (IVH). METHODS: A systematic review of the
      literature was undertaken to analyze clinical trials on IVH. RESULTS: Five
      randomized controlled trials involving a total of 366 patients were analyzed.
      There were 183 patients in each group. Open repair of IVH was associated with
      significantly higher complication rates and longer hospital stays than
      laparoscopic repair. There was also some evidence that surgical times may be
      longer for open repair of IVH. However, statistically there was no difference in
      wound pain or recurrence rates. CONCLUSIONS: Laparoscopic repair of IVH is safe,
      with fewer complications and shorter hospital stays, and possibly a shorter
      surgical time. However, postoperative pain and recurrence rates are similar for
      both techniques. Hence, the laparoscopic approach may be considered for IVH
      repair if technically feasible, but more trials with longer follow-up evaluations
      are required to strengthen the evidence.

PMID- 18614145
TI  - Online spaced education to teach urology to medical students: a multi
      institutional randomized trial.
AB  - BACKGROUND: We investigated whether online spaced education could prospectively
      improve students' acquisition and retention of knowledge. METHODS: One hundred
      fifteen third-year medical students at 2 schools were randomized to receive
      weekly/biweekly spaced education e-mails on 2 of 4 urology topics: prostate
      cancer (PC) and prostate-specific antigen (PSA) screening, or benign prostatic
      hyperplasia (BPH) and erectile dysfunction (ED). E-mails began in month 1 of
      their third year. During their 3-month surgery clerkships, students completed a
      28-item validated pre-test on all 4 topics, 8 web-based teaching cases, and a 28
      item post-test. This test was administered again a mean of 280 days later to
      assess long-term retention. RESULTS: Under an intention-to-treat analysis,
      students who received the spaced education e-mails demonstrated significant,
      topic-specific increases in pre-test scores (P < .001 and P = .03 for PC/PSA and
      BPH/ED, respectively). Spaced education improved long-term retention of PC/PSA (P
      = .04) but not of BPH/ED (P = .60). CONCLUSIONS: Spaced education delivered
      prospectively can generate significant, topic-specific learning.

PMID- 18614146
TI  - The accuracy of preoperative core biopsy in determining histologic grade, hormone
      receptors, and human epidermal growth factor receptor 2 status in invasive breast
      cancer.
AB  - BACKGROUND: Proper determination of histologic type and biomarkers in a core
      biopsy specimen is important before preoperative systemic therapy. The purpose of
      this study was to determine the accuracy of preoperative core biopsy through
      comparative analysis of histologic grade (HG), hormone receptors, and human
      epidermal growth factor receptor 2 (HER-2) status in both the core biopsy and
      surgical specimens. METHODS: We identified 104 patients with invasive ductal
      cancer who underwent core biopsy and definitive surgery in our institution. The
      histologic type, HG, estrogen receptor (ER), progesterone receptor (PR), and HER
      2 status were determined in both the core biopsy and surgical specimens by one
      pathologist. RESULTS: The mean age of the 104 patients was 50 +/- 9.9 years and
      the mean number of core biopsies was 5.1 +/- .9. The concordance rates for
      histologic type, HG, ER, PR, and HER-2 status were 100%, 80.8%, 99%, 97.1%, and
      86.5%, respectively. CONCLUSIONS: Core biopsy can predict histologic type, HG,
      ER, PR and HER-2 status preoperatively in breast cancer when used properly.

PMID- 18614147
TI  - Approach to debridement in necrotizing fasciitis.
AB  - Aggressive debridement is a cornerstone intervention in necrotizing fasciitis.
      Our approach consists of 4 steps: (1) confirming the diagnosis and isolate the
      causative organism; (2) defining the extent of fasciitis; (3) surgical excision;
      and (4) post-excision wound care. The extent of the infection is defined by
      probing the wound bluntly. Systematic excision follows. Fascial excision must be
      complete and uncompromising with the full extent of the involved wound laid open.
      We classify the infected skin into zones 1, 2, and 3. Zone 1 is necrotic tissue.
      Zone 2 is infected but potentially salvageable soft tissue, and zone 3 is non
      infected skin. Zone 1 is completely excised. Zone 2 is meticulously assessed and
      cut back as necessary to remove nonviable tissue while maximally preserving
      salvageable tissue. Zone 3 is left alone. The aim of surgical debridement is to
      remove all infected tissue in a single operation. This halts the progression of
      the fasciitis and minimizes unnecessary returns to the operating room.

PMID- 18614148
TI  - An analysis of clinical features of pulmonary giant hydatid cyst in adult
      population.
AB  - BACKGROUND: We performed an analysis of giant hydatid cysts (GCHs) detected in
      the adult population by comparison with the features of other simple hydatid
      cysts (CHs) in the light of the relevant literature. METHODS: The records of 74
      adult patients who were operated on in our clinic for pulmonary CHs between 2001
      and 2005 were retrospectively evaluated. Cysts that were 10 cm or larger in
      diameter on any plane were considered GCHs. The cysts were classified into 2
      groups as GCHs (group A) and other (group B). The groups were then compared for
      age, sex, symptom, cyst location, preoperative complications, surgical procedure
      performed, operative morbidity, and mortality. RESULTS: Of 74 patients, 10
      (13.5%) were in group A and 64 were in group B. No differences were detected
      between the clinical presentation, gender distribution, surgical procedure
      performed, and postoperative morbidity and mortality rates of GCHs and other
      cysts in adults. In both groups, there were no significant differences between
      the rates of involvement of 2 lungs (P = .527). However, both groups had lower
      lobe involvement, more markedly in group A (81.8% and 45.5% respectively; P =
      .023). Two patients in group A (20%) and 18 patients in group B (28.1%) had
      complicated cysts. CONCLUSIONS: The tendency of GCH to involve the lower lobe of
      the lung compared to smaller cysts suggests underlying mechanisms other than lung
      elasticity in the late onset of the symptoms parallel to cyst growth.

PMID- 18614149
TI  - Radiofrequency energy delivery to the anal canal: is it a promising new approach
      to the treatment of fecal incontinence?
AB  - BACKGROUND: The present study was conducted to assess the efficacy and safety of
      the delivery of radiofrequency energy to the anal canal (the SECCA procedure).
      METHODS: Eight patients with fecal incontinence underwent the SECCA procedure.
      The Fecal Incontinence Severity Index (FISI) score and the Fecal Incontinence
      related Quality of Life (FIQL) scale were completed at baseline and after the
      procedure. Anorectal manometry and endoanal ultrasound also were conducted.
      RESULTS: Seven of the 8 patients were women, and the median age of the patients
      was 59 years (range, 28-73 y). The mean FISI score and all of the parameters in
      the FIQL scale with the exception of the embarrassment scale measured at 6 months
      after the procedure was not improved significantly. We observed no changes in the
      anal manometry and endoanal ultrasound parameters. Complications associated with
      the procedure developed in 7 of the 8 patients, including anal bleeding, anal
      pain, and anal mucosal discharge. CONCLUSIONS: The FISI score and FIQL scale were
      not improved significantly after the SECCA procedure, and considerable
      complications were associated with the procedure.

PMID- 18614150
TI  - Circulating thyroglobulin mRNA does not predict early and midterm recurrences in
      patients undergoing thyroidectomy for cancer.
AB  - BACKGROUND: The aim of the present study was to evaluate if serum Tg mRNA assay
      predicts recurrence in patients undergoing thyroidectomy for cancer. METHODS:
      Sixty-four consecutive patients undergoing surgery between April 1997 and July
      1999 were studied. One year after surgery, blood samples were taken for serum
      thyroglobulin (Tg) immunoassay and for Tg mRNA assay by reverse transcription
      polymerase chain reaction (RT-PCR). All patients underwent periodical clinical
      examination, including laboratory tests for serum Tg immunoassay, neck
      ultrasound, radioiodine scans, and treatment if indicated. Kaplan-Meier estimates
      of survival were calculated according to the presence or absence of circulating
      Tg mRNA and according to baseline Tg levels. RESULTS: Tg mRNA was detected in 14
      (21.8%) of 64 patients with thyroid carcinoma. After a median follow-up of 110
      months, 8 patients (12.5%) relapsed. Among patients with detectable Tg mRNA (n.
      14), only 1 distant metastasis occurred (7%), whereas lymph node metastases (n =
      3) or distant metastases (n = 4) were detected in 7 of 50 patients (14%) with
      undetectable Tg mRNA. Tumor relapse occurred in all 7 patients with increased
      serum Tg and only in 1 out of 57 patients (1.7%) with normal or undetectable
      serum Tg. The disease-free interval of patients positive at baseline for Tg mRNA
      was similar to that of patients with undetectable Tg mRNA at baseline. Similar
      results were obtained when we limited the analysis to only patients who received
      postsurgical radioiodine ablation. CONCLUSIONS: The results of present study
      suggest that detection of circulating Tg mRNA 1 year after thyroidectomy for
      cancer might be of no utility in predicting early and midterm local and distant
      recurrences.

PMID- 18614151
TI  - [Comparative study of exercise-induced ischaemia in coronaropathy and aortic
      stenosis].
AB  - OBJECTIVE: To compare exercise and recovery data between a population of patients
      with proven CAD and patients with pure aortic stenosis (AS). PATIENTS AND
      METHODS: Exercise testing results (bicycle ergometry) of 45 patients with AS (34
      men, 66+/-12 years, 56+/-20 mmHg peak-to-peak gradient and valve area 0.78+/
      0.48cm2) were compared to exercise testing results of 50 patients with CAD (41
      men, 65+/-9 years, greater or equal to 70% stenosis on one vessel in 62%, two
      vessels in 30%, three vessels in 8%). RESULTS: During exercise, 38% patients with
      AS and 82% patients with CAD had clinical symptoms. In the AS group, exercise
      duration was longer, heart rate (HR) was higher, maximal systolic and diastolic
      blood pressure were lower than in CAD group. The increase of systolic blood
      pressure was lower in the AS group (34+/-21 mmHg versus 47+/-27 mmHg, p<0.02).
      Maximal load achieved was not significantly different. Exercise ST depression
      appeared in 76% of AS group and 88% of CAD group (NS). No difference was found in
      ST depression, Detrano index and ST segment/HR slope. During recovery, no
      difference was found in HR variations. Clockwise rotation of the ST/HR recovery
      loop was more frequent in CAD group (35 patients versus 19 patients, p<0.001).
      CONCLUSION: Most of the exercise and recovery data are similar in patients with
      AS and CAD. Significant discriminating criteria were the increase of systolic
      blood pressure during exercise and ST/HR recovery loop.

PMID- 18614152
TI  - [Recurrent transient ischemic stroke in a young patient with papillary
      fibroelastoma of the mitral valve and hyperhomocysteinemia. A case report].
AB  - We describe a case of a young patient admitted for recurrent ischemic stroke
      caused by a papillary fibroelastoma of the mitral valve and a
      hyperhomocysteinemia. A papillary fibroelastoma is a benign cardiac tumor which
      can be associated with serious embolic complications. A moderate plasma level of
      hyperhomocysteinemia is considered as a risk factor of ischemic stroke. The
      authors suggest that this association increases the risk of ischemic stroke in
      their patient. The tumor was surgically removed to avoid new embolic events
      associated with a vitamin B supplementation. After surgery and acid folic
      supplementation, no recurrence was observed.

PMID- 18614153
TI  - [Chronic use of proton-pump inhibitors associated with giardiasis: A rare cause
      of hypomagnesemic hypoparathyroidism?].
AB  - Hypomagnesemia is a rare cause of hypoparathyroidism that can have a very serious
      clinical presentation. We report the case of a 62-year-old woman hospitalized for
      exploration of acute tetraparesis with vomiting and swallowing disorders
      associated with a severe hypocalcemia. Biological explorations revealed
      hypoparathyroidism (PTH=16ng/L) related to low plasma and erythrocyte magnesium
      (0.32 and 1.32mmol/L, respectively) as well as hypocalciuria and hypomagnesuria
      linked to gastrointestinal malabsorption. Etiologic investigations led to the
      discovery of Giardiasis lamblia on duodenal biopsies and a long-term treatment
      with proton pump inhibitors (PPI) (omeprazole followed by esomeprazole), both
      being recently described as causal factors of hypomagnesemic hypoparathyroidism.
      After treatment of the parasite (by metronidazole) and discontinuation of the
      PPI, both calcium and magnesium levels returned to normal. Selective
      malabsorption has been previously reported in patients with giardiasis. The
      specific mechanism of PPI participation in the genesis of hypomagnesemia remains
      a subject of debate.

PMID- 18614154
TI  - [Tracheopathia osteoplastica].
AB  - OBJECTIVES: Report a case of tracheopathia osteoplastica and describe from a
      literature analysis the main clinical, radiological, and therapeutic features of
      this rare disease based on literature review. MATERIAL AND METHODS: A 74-year-old
      patient suffering from a nasal polyposis that had been repeatedly operated was
      admitted for surgery of the frontal sinus. The day of surgery, the difficult
      intubation required a laryngotracheoscopy, which found a dystrophic trachea, with
      a sprinkling of whitish nodules, and hard swelling. The pathologic exams of a
      large biopsy specimen using a rigid bronchoscopy provided the diagnosis of
      tracheopathia osteoplastic. A complementary workup to search for the etiology was
      undertaken. The risk and the difficulty of the intubation led to suspending the
      surgery. RESULTS: The CT scan as well as the histological, bacteriological, and
      immunological tests showed nothing specific. The etiopathogenic hypothesis was
      the association of chronic disease of the upper airways such as the ozena or the
      chronic inflammation of the respiratory tract, an endocrine factor,
      dermatomyositis, exposure to toxic substances such as silica, or tracheobronchial
      amyloidosis. The bronchial microbiology test is positive in more than 50% of
      patients, and often Klebsiella ozaenae or Pseudomonas aeruginosa is found.
      CONCLUSION: Tracheopathia osteoplastica is a rare tumor, with unknown etiology
      and physiopathology. The discovery is most often incidental. Progession is slow
      and it does not compromise the vital prognosis. The treatment is symptomatic. Few
      surgical tracheal operations are described in the literature.

PMID- 18614155
TI  - Functions of acidic transmembrane residues in human melanocortin-3 receptor
      binding and activation.
AB  - The melanocortin-3 receptor (MC3R) is an important regulator of energy
      homeostasis, inflammation, and cardiovascular function. Inactivating mutations in
      MC3R gene are associated with childhood obesity. How MC3R binds to its ligands
      has rarely been studied. In the present study, we systematically mutated all ten
      acidic residues in transmembrane (TM) domains and measured the cell surface
      expression levels as well as ligand binding and signaling properties of these
      mutants. Our results showed that of the 19 mutants stably expressed in HEK293
      cells, all were expressed on the cell surface, although some mutants had
      decreased levels of cell surface expression. We showed that with the superpotent
      analog [Nle(4), D-Phe(7)]-alpha-melanocyte stimulating hormone (MSH), E92, E131,
      D154, D158, D178, and D332 are important for ligand binding. D121 and D332 are
      important for binding and signaling. Further experiments using other ligands such
      as D-Trp(8)-gamma-MSH, alpha-MSH and gamma-MSH showed that different ligands
      induce or select different conformations. In summary, we showed that acidic
      residues in TMs 1 and 3 are important for ligand binding whereas the acidic
      residues in TMs 2 and 7 are important for both ligand binding and signaling.

PMID- 18614156
TI  - Sentence processing in the visual and auditory modality: do comma and prosodic
      break have parallel functions?
AB  - Two Event-Related Potential (ERP) studies contrast the processing of locally
      ambiguous sentences in the visual and the auditory modality. These sentences are
      disambiguated by a lexical element. Before this element appears in a sentence,
      the sentence can also be disambiguated by a boundary marker: a comma in the
      visual modality, or a prosodic break in the auditory modality. Previous studies
      have shown that a specific ERP component, the Closure Positive Shift (CPS), can
      be elicited by these markers. The results of the present studies show that both
      the comma and the prosodic break disambiguate the ambiguous sentences before the
      critical lexical element, despite the fact that a clear CPS is only found in the
      auditory modality. Comma and prosodic break thus have parallel functions
      irrespective of whether they do or do not elicit a CPS.

PMID- 18614157
TI  - Eye movement preparation causes spatially-specific modulation of auditory
      processing: new evidence from event-related brain potentials.
AB  - To investigate whether saccade preparation can modulate processing of auditory
      stimuli in a spatially-specific fashion, ERPs were recorded for a Saccade task,
      in which the direction of a prepared saccade was cued, prior to an imperative
      auditory stimulus indicating whether to execute or withhold that saccade. For
      comparison, we also ran a conventional Covert Attention task, where the same cue
      now indicated the direction for a covert endogenous attentional shift prior to an
      auditory target-nontarget discrimination. Lateralised components previously
      observed during cued shifts of attention (ADAN, LDAP) did not differ
      significantly across tasks, indicating commonalities between auditory spatial
      attention and oculomotor control. Moreover, in both tasks, spatially-specific
      modulation of auditory processing was subsequently found, with enhanced
      negativity for lateral auditory nontarget stimuli at cued versus uncued
      locations. This modulation started earlier and was more pronounced for the Covert
      Attention task, but was also reliably present in the Saccade task, demonstrating
      that the effects of covert saccade preparation on auditory processing can be
      similar to effects of endogenous covert attentional orienting, albeit smaller.
      These findings provide new evidence for similarities but also some differences
      between oculomotor preparation and shifts of endogenous spatial attention. They
      also show that saccade preparation can affect not just vision, but also sensory
      processing of auditory events.

PMID- 18614158
TI  - Localization and cellular distribution of CPNE5 in embryonic mouse brain.
AB  - CPNE5 is one of the ubiquitous Ca(2+)-dependent, phospholipid-binding proteins
      that are highly conserved in animals. It was cloned in the fetal human brain with
      no exact functions identified yet. We have examined the distribution pattern of
      CPNE5 mRNA and protein in the developing murine brain by using in situ
      hybridization, western blotting and immunocytochemistry. Expression of CPNE5 mRNA
      remains high from embryonic day 9.5 (E9.5) to E15.5 in the developing murine
      brain. Whole-mount in situ hybridization with the E11.5 and E12.5 embryos showed
      the strong positive signals in the central nervous system. Western-blot analysis
      showed that CPNE5 protein is expressed in the developing but not in the adult
      murine brain. In situ hybridization and immunohistochemistry analysis on the
      embryonic brain sections indicated that both at RNA and protein levels CPNE5 is
      mainly expressed in frontal cortex, medial nasal prominence, ganglionic eminence
      and medulla, particularly in the ventricular zones. Further investigation
      revealed the co-localization of CPNE5 with Tuj1 and Nestin on embryonic brain
      sections. In addition to the slight expression in primary cultured neural
      progenitor cells, CPNE5 is found in soma and neurite projections of primary
      cultured neurons where Tuj1 is co-localized. Our results demonstrate that CPNE5
      is expressed in both neural progenitor cells and the differentiated neurons
      during the neural development, which suggests that CPNE5 might play an important
      role in the development of murine central nervous system.

PMID- 18614159
TI  - Role of orexin input in the diurnal rhythm of locus coeruleus impulse activity.
AB  - Activation of noradrenergic locus coeruleus (LC) neurons promotes wakefulness and
      behavioral arousal. In rats, LC neurons receive circadian inputs via a circuit
      that originates in the suprachiasmatic nucleus (SCN) and relays through the
      dorsomedial hypothalamus (DMH) to LC; this circuit input increases LC activity
      during the active period. DMH neurons expressing the peptide neurotransmitter
      orexin/hypocretin are ideally situated to act as a relay between SCN and LC due
      to their synaptic inputs from SCN and innervation of LC. Here, we examined the
      hypothesis that orexin is involved in transmitting circadian signals to LC using
      single-unit recordings of LC neurons in anesthetized rats maintained in 12:12
      light-dark housing. We replicated earlier findings from this lab that LC neurons
      fire significantly faster on average during the active compared to rest periods.
      Local microinjection of an orexin antagonist, SB-334867-A attenuated the impulse
      activities of the fastest firing population of LC neurons during the active
      period. We also found that DMH orexin neurons project preferentially to LC and
      express a diurnal rhythm of activation that correlates with LC neuronal firing
      frequency. Therefore, we propose that DMH orexin neurons play a role in
      modulating the day-night differences of LC impulse activity.

PMID- 18614160
TI  - Comparison processes in category learning: from theory to behavior.
AB  - Recent studies stressed the importance of comparing exemplars both for improving
      performance by artificial classifiers as well as for explaining human category
      learning strategies. In this report we provide a theoretical analysis for the
      usability of exemplar comparison for category-learning. We distinguish between
      two types of comparison -- comparison of exemplars identified to belong to the
      same category vs. comparison of exemplars identified to belong to two different
      categories. Our analysis suggests that these two types of comparison differ both
      qualitatively and quantitatively. In particular, in most everyday life scenarios,
      comparison of same-class exemplars will be far more informative than comparison
      of different-class exemplars. We also present behavioral findings suggesting that
      these properties of the two types of comparison shape the category-learning
      strategies that people implement. The predisposition for use of one strategy in
      preference to the other often results in a significant gap between the actual
      information content provided, and the way this information is eventually
      employed. These findings may further suggest under which conditions the reported
      category-learning biases may be overcome.

PMID- 18614162
TI  - The arcuate fasciculus and the disconnection theme in language and aphasia:
      history and current state.
AB  - Few themes have been more central to neurological models of aphasia than the
      disconnection paradigm and the role of the arcuate fasciculus. Introduced by
      luminaries of 19th Century neurology and resurrected by the charismatic work of
      Norman Geschwind, the disconnection theme has triggered spectacular advances of
      modern understanding of language and aphasia. But the disconnection paradigm had
      alternate fortunes, ranging from irrational exuberance to benign neglect, and its
      followers have not always shared the same view on its functional consequences and
      anatomical correlates. Our goal in this paper is, first, to survey the 19th
      Century roots of the connectionist approach to aphasia and, second, to describe
      emerging imaging technologies based on diffusion tensor imaging (DTI) that
      promise to consolidate and expand the disconnection approach to language and its
      disorders.

PMID- 18614163
TI  - Mix.1/2-dependent control of FGF availability during gastrulation is essential
      for pronephros development in Xenopus.
AB  - Although FGFs are known to affect mesoderm patterning, their influence on
      intermediate mesoderm specification during gastrulation is ignored. Here, we show
      that pronephros precursors are exposed to FGF, but a strict control of FGF
      signals is necessary to allow pronephros development. We provide evidence that
      this control is mediated by the paired-like homeobox genes Mix.1 and Mix.2.
      Morpholino-based Mix.1/2 knockdown, or repression of Mix.1 target genes with an
      enRMix.1 construct, causes an expansion of FGF4 and FGF8 expression in the
      lateral marginal zone at gastrula stage, together with an inhibition of
      pronephros development at neurula and tailbud stages. Expression of the
      nephrogenic mesoderm markers Xlim-1 and XPax-8 can be rescued in Mix.1/2
      morphants by intrablastocoelic injections of the FGFR inhibitor SU5402 at mid
      gastrula stage, showing that inhibition of pronephros development results from an
      increase of FGF signalling. We further show that Mix.1 overexpression results in
      the down-regulation of FGF3, 4, 8 and XmyoD, in addition to Xbra. However, cells
      overexpressing Mix.1 can normally populate somites, indicating that Mix.1 does
      not affect their fate cell autonomously. These data support the idea that Mix.1/2
      regulates levels and/or duration of FGF signals to which pronephros precursors
      are exposed during gastrulation.

PMID- 18614161
TI  - Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar
      systems.
AB  - Disconnection syndromes were originally conceptualized as a disruption of
      communication between different cerebral cortical areas. Two developments mandate
      a re-evaluation of this notion. First, we present a synopsis of our anatomical
      studies in monkey elucidating principles of organization of cerebral cortex.
      Efferent fibers emanate from every cortical area, and are directed with
      topographic precision via association fibers to ipsilateral cortical areas,
      commissural fibers to contralateral cerebral regions, striatal fibers to basal
      ganglia, and projection subcortical bundles to thalamus, brainstem and/or
      pontocerebellar system. We note that cortical areas can be defined by their
      patterns of subcortical and cortical connections. Second, we consider motor,
      cognitive and neuropsychiatric disorders in patients with lesions restricted to
      basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic
      deficits resulting from cortical lesions, with qualitative differences between
      the manifestations of lesions in functionally related areas of cortical and
      subcortical nodes. We consider these findings on the basis of anatomical
      observations from tract tracing studies in monkey, viewing them as disconnection
      syndromes reflecting loss of the contribution of subcortical nodes to the
      distributed neural circuits. We introduce a new theoretical framework for the
      distributed neural circuits, based on general, and specific, principles of
      anatomical organization, and on the architecture of the nodes that comprise these
      systems. We propose that neural architecture determines function, i.e., each
      architectonically distinct cortical and subcortical area contributes a unique
      transform, or computation, to information processing; anatomically precise and
      segregated connections between nodes define behavior; and association fiber
      tracts that link cerebral cortical areas with each other enable the cross-modal
      integration required for evolved complex behaviors. This model enables the
      formulation and testing of future hypotheses in investigations using evolving
      magnetic resonance imaging techniques in humans, and in clinical studies in
      patients with cortical and subcortical lesions.

PMID- 18614165
TI  - Distribution of polychlorinated biphenyls and organochlorine pesticides in human
      breast milk from various locations in Tunisia: levels of contamination,
      influencing factors, and infant risk assessment.
AB  - The concentrations of dichlorodiphenytrichloroethane and its metabolites (DDTs),
      hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), dieldrin, and 20
      polychlorinated biphenyls (PCBs) were determined in 237 human breast milk samples
      collected from 12 locations in Tunisia. Gas chromatography with electron capture
      detector (GC-ECD) was used to identify and quantify residue levels on a lipid
      basis of organochlorine compounds (OCs). The predominant OCs in human breast milk
      were PCBs, p,p'-DDE, p,p'-DDT, HCHs, and HCB. Concentrations of DDTs in human
      breast milk from rural areas were significantly higher than those from urban
      locations (p<0.05). With regard to PCBs, we observed the predominance of mid
      chlorinated congeners due to the presence of PCBs with high K(ow) such as PCB
      153, 138, and 180. Positive correlations were found between concentrations of OCs
      in human breast milk and age of mothers and number of parities, suggesting the
      influence of such factors on OC burdens in lactating mothers. The comparison of
      daily intakes of PCBs, DDTs, HCHs, and HCB to infants through human breast milk
      with guidelines proposed by WHO and Health Canada shows that some individuals
      accumulated OCs in breast milk close to or higher than these guidelines.

PMID- 18614164
TI  - Nuclear regulator Pygo2 controls spermiogenesis and histone H3 acetylation.
AB  - Mammalian spermiogenesis, a process where haploid male germ cells differentiate
      to become mature spermatozoa, entails dramatic morphological and biochemical
      changes including remodeling of the germ cell chromatin. Proteins that contain
      one or more plant homeodomain (PHD) fingers have been implicated in the
      regulation of chromatin structure and function. Pygopus 2 (Pygo2) belongs to a
      family of evolutionarily conserved PHD finger proteins thought to act as co
      activators of Wnt signaling effector complexes composed of beta-catenin and
      LEF/TCF transcription factor. Here we analyze mice containing hypomorphic alleles
      of pygopus 2 (Pygo2 or mpygo2) and uncover a beta-catenin-independent involvement
      of the Pygo2 protein in spermiogenesis. Pygo2 is expressed in elongating
      spermatids at stages when chromatin remodeling occurs, and block of Pygo2
      function leads to spermiogenesis arrest and consequent infertility. Analysis of
      spermiogenesis in Pygo2 mutants reveals reduced expression of select post-meiotic
      genes including protamines, transition protein 2, and H1fnt, all of which are
      required for germ cell chromatin condensation, and drastically altered pattern of
      histone H3 hyperacetylation. These findings suggest that Pygo2 is involved in the
      chromatin remodeling events that lead to nuclear compaction of male germ cells.

PMID- 18614166
TI  - Comparison of the involvement of protein kinase C in agonist-induced contractions
      in mouse aorta and corpus cavernosum.
AB  - Protein kinase C (PKC) is involved in the regulation of vascular smooth muscle
      contraction. However, the role of PKC in erectile function is poorly understood.
      This study investigated whether PKC mediates agonist-induced contractions in
      mouse penile tissue (corpora cavernosa). We also compared the effects of PKC
      activators and inhibitors on contractile responses in mouse corpus cavernosum
      with those in mouse aorta. Aortic rings and corpus cavernosal strips from
      C57BL/6J mice were mounted in the organ bath for isometric tension recording. Our
      data showed that a PKC(alpha/beta) selective inhibitor, G(o)6976 (10 microM),
      inhibited phenylephrine and 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin
      F(2alpha) (U46619, a thromboxane mimetic)-induced contractions in mouse aorta,
      reducing the maximum contraction by 94% and 17%, respectively. A non-selective
      PKC inhibitor, chelerythrine (30 microM), also significantly reduced
      phenylephrine- and U46619-induced maximum contractions in mouse aorta. However,
      G(o)6976 and chelerythrine had no significant effects on phenylephrine- and
      U46619-induced contractions in corpus cavernosum. Furthermore, a PKC activator,
      phorbol-12,13-dibutyrate (0.1 microM), significantly increased contractions in
      aorta (208+/-14% of KCl-induced maximum contraction) but failed to cause
      contractions in corpus cavernosum at 1 and 10 microM. Western blot analysis data
      suggested that protein expression of PKC was similar in aorta and corpus
      cavernosum. Taken together, our data indicate that PKC does not have a
      significant role in agonist-induced contractions in mouse corpus cavernosum,
      whereas it mediates the contractile response to agonists in the aorta.

PMID- 18614167
TI  - Reactivity of retinal blood flow to 100% oxygen breathing after
      lipopolysaccharide administration in healthy subjects.
AB  - Administration of low doses of Escherichia coli endotoxin (LPS) to humans enables
      the study of inflammatory mechanisms. The purpose of the present study was to
      investigate the retinal vascular reactivity after LPS infusion. In a randomized
      placebo-controlled cross-over study, 18 healthy male volunteers received 20 IU/kg
      LPS or placebo as an intravenous bolus infusion. Outcome parameters were measured
      at baseline and 4h after LPS/placebo administration. At baseline and at 4h after
      administration a short period of 100% oxygen inhalation was used to assess
      retinal vasoreactivity to this stimulus. Perimacular white blood cell velocity,
      density and flux were assessed with the blue-field entoptic technique, retinal
      branch arterial and venous diameters were measured with a retinal vessel analyzer
      and red blood cell velocity in retinal branch veins was measured with laser
      Doppler velocimetry. LPS is associated with peripheral blood leukocytosis and
      increased white blood cell density in ocular microvessels (p<0.001). In addition,
      retinal arterial (p=0.02) and venous (p<0.01) diameters were increased. All
      retinal hemodynamic parameters showed a decrease during 100% oxygen breathing.
      This decrease was significantly blunted by LPS for all retinal outcome parameters
      except venous diameter (p=0.04 for white blood cell velocity, p=0.0002 for white
      blood cell density, p<0.0001 for white blood cell flux, p=0.01 for arterial
      diameter, p=0.02 for red blood cell velocity and p=0.006 for red blood cell
      flux). These data indicate that LPS-induced inflammation induces vascular
      dysregulation in the retina. This may provide a link between inflammation and
      vascular dysregulation. Further studies are warranted to investigate whether this
      model may be suitable to study inflammation induced vascular dysregulation in the
      eye.

PMID- 18614168
TI  - Lens ion transport: from basic concepts to regulation of Na,K-ATPase activity.
AB  - In the late 1960s, studies by George Duncan explained many of the basic
      principles that underlie lens ion homeostasis. The experiments pointed to a
      permeability barrier close to the surface of the lens and illustrated the
      requirement for continuous Na,K-ATPase-mediated active sodium extrusion. Without
      active sodium extrusion, lens sodium and calcium content increases resulting in
      lens swelling and deterioration of transparency. Later, Duncan's laboratory
      discovered functional muscarinic and purinergic receptors at the surface of the
      lens. Recent studies using intact lens suggest purinergic receptors might be
      involved in short-term regulation of Na,K-ATPase in the epithelium. Purinergic
      receptor agonists ATP and UTP selectively activate certain Src family tyrosine
      kinases and stimulate Na,K-ATPase activity. This might represent part of a
      control mechanism capable of adjusting, perhaps fine tuning, lens ion transport
      machinery.

PMID- 18614170
TI  - Sticky chain model for shear response of red blood cells.
AB  - A sticky chain model has been proposed to describe the unfolding of spectrin
      network under applied mechanical loads. With the model, the response of a red
      blood cell (RBC) under static and cyclic shear loading has been predicted, which
      agrees qualitatively with relevant experimental results.

PMID- 18614169
TI  - Conditional deletion of the NMDA-NR1 receptor subunit gene in the central nucleus
      of the amygdala inhibits naloxone-induced conditioned place aversion in morphine
      dependent mice.
AB  - Preclinical behavioral pharmacological and neuropharmacological evidence
      indicates that the NMDA receptor plays an important role in opioid dependence,
      however, the neural substrates subserving these actions are poorly understood.
      The central nucleus of the amygdala (CeA) is a critical coordinator of autonomic,
      behavioral, and emotional systems impacted by opioids, however there is no
      evidence that the essential NMDA-NR1 (NR1) subunit gene in the amygdala plays a
      role in opioid dependence. To determine the role of the NR1 subunit gene in the
      amygdala with respect to physical and psychological opioid withdrawal, a spatial
      temporal deletion of this gene was produced by microinjecting a recombinant adeno
      associated virus (rAAV) expressing the GFP reporter and Cre recombinase (rAAV-GFP
      Cre) into the CeA of adult "floxed" NR1 mice (fNR1). Amygdala microinjection of
      rAAV-GFP-Cre produced a decrease in NR1 gene expression and protein
      immunolabeling in postsynaptic sites of neurons without signs of compromised
      ultrastructural neuronal morphology. Amygdala NR1 gene deletion also did not
      affect locomotor, somatosensory, or sensory-motor behaviors. In addition,
      bilateral local NR1 gene deletion did not impact somatic or visceral withdrawal
      symptoms precipitated by naloxone in morphine-dependent mice. However, there was
      a significant deficit in the expression of an opioid withdrawal-induced
      conditioned place aversion in mice with amygdala NR1 deletion. These results
      indicate that functional amygdala NMDA receptors are involved in aversive
      psychological processes associated with opioid withdrawal. More generally,
      spatial-temporal deletion of the NR1 subunit by Cre-loxP technology is an
      effective means to elucidate the neurogenetic substrates of complex phenotypes
      associated with drug abuse.

PMID- 18614171
TI  - Wear paths produced by individual hip-replacement patients--a large-scale, long
      term follow-up study.
AB  - Wear particle accumulation is one of the main contributors to osteolysis and
      implant failure in hip replacements. Altered kinematics produce significant
      differences in wear rates of hip replacements in simulator studies due to varying
      degrees of multidirectional motion. Gait analysis data from 153 hip-replacement
      patients 10-years post-operation were used to model two- and three-dimensional
      wear paths for each patient. Wear paths were quantified in two dimensions using
      aspect ratios and in three dimensions using the surface areas of the wear paths,
      with wear-path surface area correlating poorly with aspect ratio. The average
      aspect ratio of the patients wear paths was 3.97 (standard deviation=1.38),
      ranging from 2.13 to 10.86. Sixty percent of patients displayed aspect ratios
      between 2.50 and 3.99. However, 13% of patients displayed wear paths with aspect
      ratios >5.5, which indicates reduced multidirectional motion. The majority of
      total hip replacement (THR) patients display gait kinematics which produce
      multidirectional wear paths, but a significant minority display more linear
      paths.

PMID- 18614172
TI  - Numerical investigation of the three-dimensional flow in a human lung model.
AB  - The flow field at inspiration and expiration in the upper human airways
      consisting of the trachea down to the sixth generation of the bronchial tree is
      numerically simulated. The three-dimensional steady flow at a hydraulic diameter
      based Reynolds number Re(D)=1250 is computed via a lattice-Boltzmann method
      (LBM). The simulation is validated by the experimental data based on particle
      image velocimetry (PIV) measurements. The good agreement between numerical and
      experimental results is evidenced by comparing velocity contours and
      distributions in a defined reference plane. The results show the LBM to be an
      accurate tool to numerically predict flow structures in the human lung. Using an
      automatic Cartesian grid generator, the overall process time from meshing to a
      steady-state solution is <12h. Moreover, the numerical simulation allows a closer
      analysis of the secondary flow structures than in the experimental investigation.
      The three-dimensional streamline patterns reveal some insight on the air exchange
      mechanism at inspiration and expiration. At inspiration, the slower near-wall
      tracheal flow enters through the right principal bronchus into the right upper
      lobar bronchus. The bulk mass flux in the trachea is nearly evenly distributed
      over the left upper, center and lower lobar bronchi and the right center and
      lower bronchi. At expiration, the air from the right upper lobar bronchus enters
      the right center of the trachea and displaces the airflow from the lower and
      center right bronchi such that the tracheal positions of the streamlines at
      inspiration and expiration are switched. The flow in the left bronchi does not
      show this kind of switching. The findings emphasize the impact of the asymmetry
      of the lung geometry on the respiratory air exchange mechanism.

PMID- 18614173
TI  - First extant records of mermithid nematode parasitism of Auchenorrhyncha in
      Europe.
AB  - Parasitic nematodes of the family Mermithidae were found within four specimens of
      Auchenorrhyncha from two families (Cicadellidae and Delphacidae). This appears to
      be the the first extant example of mermithid parasitism of Auchenorrhyncha in
      Europe. The insect hosts were collected from agricultural grassland field margins
      at three locations in Ireland during a farmland biodiversity study in 2007.

PMID- 18614174
TI  - Discovery of a novel Bacillus thuringiensis Cry8D protein and the unique toxicity
      of the Cry8D-class proteins against scarab beetles.
AB  - A novel cry gene, cry8Db, highly toxic to scarab beetles such as the Japanese
      beetle, Popillia japonica Newman, was cloned from an isolate of Bacillus
      thuringiensis(Bt), BBT2-5. The cry8Db gene has 3525bp nucleotides and codes for a
      protein of 1174 amino acid residues. The protein, Cry8Db, has typical Bt
      characteristics such as the 8-block, conserved sequences and the three-domain 3D
      toxin structure as defined with Cry3Aa. When the amino acid sequence of Cry8Db
      was compared with that of Cry8Da whose gene was cloned and characterized in our
      laboratory earlier, substantial sequence diversities were found in their Domain
      III. The cry8Db gene was expressed in an acrystalliferous B. thuringiensis
      strain, BT51. BT51 expressing cry8Db formed a spherical crystal like the natural
      crystal of BBT2-5. The Cry8Db protein was assayed along with the other scarab
      active Cry8Da and Cry8Ca against the Japanese beetle. While Cry8Da and Cry8Db had
      toxicity against both adults and larvae of the Japanese beetle, Cry8Ca was toxic
      to only larvae. Cry8Ca showed no toxicity against the adult beetle up to 30
      microg per 1 cm(2) of leaf discs on which the protein was applied. The activation
      process of Cry8Db by adult and larval gut juice was compared in vitro with the
      processes of Cry8Da and Cry8Ca. All three proteins, Cry8Db, Cry8Da and Cry8Ca,
      produced a toxic core of approximately 70kDa equally indicating that the
      activation process does not inactivate the adult activity of Cry8Ca. We concluded
      that the adult activity of Cry8D proteins is encoded in Domain II. Further tests
      against other beetle species showed a significant difference between Cry8D's and
      Cry8Ca but no difference between Cry8Da and Cry8Db. Comparison of 3D structural
      models of Cry8Ca, Cry8Da and Cry8Db, which were constructed by using Cry3Bb as
      the structural template, indicated significant structural differences, especially
      between Cry8Ca and Cry8D proteins, in three major surface-exposed loops of Domain
      II that may be involved in determining the adult beetle activity.

PMID- 18614175
TI  - Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its
      binding to ERM proteins.
AB  - CD43/leukosialin/sialophorin is the major adhesion molecule in most hematopoietic
      cells and belongs to the sialomucin superfamily. In leukocyte emigration and
      activation, the exclusion of CD43 from the immunological synapse is an essential
      step. While the exclusion requires binding of the cytoplasmic region to ERM
      (ezrin/radixin/moesin) proteins, the detailed specific nature of the interaction
      between CD43 and ERM proteins is obscure. We have characterized the
      conformational properties of the CD43 cytoplasmic region, consisting of 124 amino
      acid residues, by hydrodynamic and spectroscopic measurements. Sedimentation
      equilibrium and velocity studies of ultracentrifugation revealed that the CD43
      cytoplasmic peptide exists in a monomeric and extended form in solution. The
      crystal structure of the complex between the radixin FERM (4.1 and ERM) domain
      and the CD43 juxtamembrane region peptide reveals that the nonpolar region of the
      peptide binds subdomain C of the FERM domain. CD43 lacks the Motif-1 sequence for
      FERM binding found in the FERM-intercellular adhesion molecule-2 complex but
      possesses two conserved leucine residues that dock into the hydrophobic pocket of
      subdomain C without forming a 3(10)-helix. The FERM-binding site on CD43 is
      overlapped with the functional nuclear localization signal sequence. Our
      structure suggests that regulation of ERM binding may be coupled with regulated
      intramembrane proteolysis of CD43 followed by the nuclear transfer of the
      cytoplasmic peptide.

PMID- 18614176
TI  - Uracil recognition in archaeal DNA polymerases captured by X-ray crystallography.
AB  - Archaeal family B DNA polymerases bind tightly to template-strand uracil and
      stall replication on encountering the pro-mutagenic base. This article describes
      an X-ray crystal structure, at 2.8 A resolution, of Thermococcus gorgonarius
      polymerase in complex with a DNA primer-template containing uracil in the single
      stranded region. The DNA backbone is distorted to position the uracil deeply
      within a pocket, located in the amino-terminal domain of the polymerase.
      Specificity arises from a combination of hydrogen bonds between the protein
      backbone and uracil, with the pocket shaped to prevent the stable binding of the
      four standard DNA bases. Strong interactions are seen with the two phosphates
      that flank the uracil and the structure gives clues concerning the coupling of
      uracil binding to the halting of replication. The importance of key amino acids,
      identified by the analysis of the structure and their conservation between
      archaeal polymerases, was confirmed by site-directed mutagenesis. The crystal
      structure of V93Q, a polymerase variant that no longer recognises uracil, is also
      reported, explaining the V93Q phenotype by the steric exclusion of uracil from
      the pocket.

PMID- 18614177
TI  - Structural polymorphism of oligomeric adiponectin visualized by electron
      microscopy.
AB  - Adiponectin, a macromolecular complex similar to the members of the C1q and other
      collagenous homologues, elicits diverse biological functions, including anti
      diabetes, anti-atherosclerosis, anti-inflammation and anti-tumor activities,
      which have been directly linked to the high molecular weight (HMW) oligomeric
      structures formed by multiples of adiponectin trimers. Here, we report the 3-D
      reconstructions of isolated full-length, recombinant murine C39A adiponectin
      trimer and hexamer of wild-type trimers (the major HMW form) determined by single
      particle analysis of electron micrographs. The pleiomorphic ensemble of collagen
      like stretches of the trimers leads to a dynamic structure of HMW that partition
      into two major classes, the fan-shaped (class I) and bouquet-shaped (class II).
      In both of these, while the N termini cluster into a compact ellipsoid-shaped
      (approximately 60 Ax45 Ax45 A) volume, the collagenous domains assume a variety
      of arrangements. The domains are splayed by up to approximately 90 degrees in
      class I, can form a close-packed, up to approximately 100x40 A cylindrical
      assembly in class II, which can house about half of the 66 putative collagen-like
      sequence and the rest, tethered to the trimeric globular domains at the C
      terminus, are highly dynamic. As a result, the globular domains elaborate a
      variety of arrangements, covering an area of up to approximately 4.9x10(5) A(2)
      and up to approximately 320 A apart, some of which were captured in
      reconstructions of class II. Our reconstructions suggest that the N-terminal
      structured domain, agreeing approximately with the expected volume for the
      octadecameric assembly of the terminal 27 amino acids, is crucial to the
      formation of the functionally active HMW. On the other hand, conformational
      flexibility of the trimers at the C terminus can allow the HMW to access and
      cluster disparate target ligands binding to the globular domains, which may be
      necessary to activate cellular signaling leading to the remarkable functional
      diversity of adiponectin.

PMID- 18614178
TI  - Weight gain in older adolescent females: the internet, sleep, coffee, and
      alcohol.
AB  - OBJECTIVES: To examine whether excessive recreational Internet time, insufficient
      sleep, regular coffee consumption, or alcoholic beverages promote weight gain.
      STUDY DESIGN: A longitudinal cohort of >5000 girls (Growing Up Today Study), from
      all over the United States and aged 14 to 21 years, returned surveys in 2001
      reporting typical past-year recreational Internet time, sleep, coffee (with
      caffeine), and alcohol consumption. We estimated correlations among these 4
      exposures. Each girl also reported her height and weight in 2000 and again in
      2001. Multivariate models investigated associations between 1-year change in body
      mass index and same-year exposures, adjusted for adolescent growth/development,
      activity, and inactivity. RESULTS: The exposures were highly (P < .0001)
      correlated with each other, except for coffee with Internet time (P > .50). More
      Internet time, more alcohol, and less sleep were all associated (P < .05) with
      same-year increases in body mass index. Females, aged 18+ years, who slept <or=5
      hours/night (P < .01) or who consumed alcohol 2+servings/week (P < .07) gained
      more body mass index from 2000 to 2001. For females in weight-promoting
      categories of all exposures, this translates to nearly 4 extra pounds gained over
      1 year. We found no evidence that drinking coffee promotes weight gain.
      CONCLUSIONS: Older girls may benefit from replacing recreational Internet time
      with sleep and by avoiding alcohol.

PMID- 18614180
TI  - Empathy and symptoms dimensions of patients with obsessive-compulsive disorder.
AB  - Patients with obsessive-compulsive disorder (OCD) often display cognitions and/or
      behaviors that may well reflect the existence of "hyper-attachment" to different
      environmental elements, including their offspring, family members, divine
      entities, or even inanimate objects. Based on the fact that both OCD symptoms and
      physiologic interpersonal attachment mechanisms involve overlapping ventral
      fronto-limbic circuits, we hypothesized that there is a relationship between
      empathy, evaluated with the Interpersonal Reactivity Index (IRI), and OCD symptom
      dimensions. We evaluated 53 patients with OCD and 53 age- and sex-matched
      individuals from the community with the Structured Clinical Interview for the
      Diagnosis of DSM-IV axis I disorders, the Saving Inventory-Revised, the IRI
      (composed of four sub-scales), the Obsessive-Compulsive Inventory - Revised, the
      Beck Depression Inventory, and the Beck Anxiety Inventory. Patients with OCD
      displayed greater levels of affective empathy (i.e., empathic concern (p=0.006)
      and personal discomfort (p<0.001)) than community controls. In bivariate
      analyses, the severity of hoarding symptoms of patients with OCD correlated with
      empathic concern (r=0.39; p<0.001), fantasy (r=0.36; p<0.01), and personal
      discomfort (r=0.39; p<0.001). In partial correlation analyses adjusting for
      comorbid depression and anxiety, only the association between hoarding and
      fantasy remained robust (r=0.41; p<0.001). A model that included severity of
      hoarding, depression, and anxiety symptoms predicted 33% of the variance on the
      fantasy scale. Our findings suggest that hoarding is linked to specific aspects
      of interpersonal reactivity. Comorbid depression and anxiety, however, explain a
      large proportion of the empathic profile exhibited by patients with OCD.

PMID- 18614179
TI  - Mental disorders and cardiovascular disease among adults in the United States.
AB  - OBJECTIVE: Numerous population-based studies have found an association between
      major depression and CVD, though these studies did not assess anxiety disorders.
      Patient samples have shown associations between anxiety disorders and
      cardiovascular disease (CVD), but without consideration of depressive disorders.
      Therefore, it remains unclear whether: (a) both anxiety and depressive disorder
      are associated with CVD; (b) these associations are generalizable to adults in
      the community. MATERIALS AND METHODS: Data were drawn from the National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally
      representative sample of 43,093 civilian non-institutionalized participants aged
      18 and older. RESULTS: CVD (total prevalence 3.3%) was associated with increased
      likelihood of any anxiety disorder (OR=1.43, (1.20, 1.71)), after adjusting for
      depressive disorders, as well as Generalized Anxiety Disorder (OR=1.48 (1.09,
      2.01)), Panic disorder (OR=1.46 (1.12, 1.91)), and specific phobia (OR=1.29
      (1.04, 1.59)). CVD was significantly associated with any mood disorder (OR=1.34
      (1.13, 1.58)) after adjusting for anxiety disorders, though neither the link with
      major depression, nor other specific mood disorders remained significant after
      adjustment. CONCLUSIONS: Our findings suggest that anxiety disorders, mood
      disorders, and CVD are highly comorbid among adults in the United States, and
      demonstrate the importance of including anxiety disorder assessment in studies of
      mental and physical comorbidity. These results reveal how the lack of
      investigation into specific relationships between CVD and the range of mental
      disorders in population-based studies of risk factors for CVD may obscure
      important relationships.

PMID- 18614181
TI  - Seasonal and spatial distribution of matrix-bound phosphine and its relationship
      with the environment in the Changjiang River Estuary, China.
AB  - Sediment is commonly considered as a source of phosphine, which is a highly toxic
      and reactive atmospheric trace gas. This study aims to investigate the seasonal
      and spatial distribution of matrix-bound phosphine (MBP) and its relationship
      with the environment in the Changjiang River Estuary. A total of 43 surface
      sediments were collected in four seasons of 2006, and concentrations of MBP and
      relative environmental factors were analyzed. MBP ranged from 1.93 to 94.86ng kg(
      1) dry weight (dw) with an average concentration of 17.14ng kg(-1)dw. The
      concentrations of MBP in the upper estuary were higher than those in the lower
      estuary, which could be attributed to greater pollutant inputs in the upper
      estuary. The concentrations of MBP also varied with season, with November >
      August > May > February. Significant correlations existed between MBP and total
      phosphorus (TP), organic phosphorus (OP), inorganic phosphorus (IP), organic
      carbon (OC), total nitrogen (TN), the grain size, and redox potential (Eh),
      suggesting that these sedimentary environmental characteristics played an
      important role in controlling the MBP levels in the sediments. Notably, there
      were positive linear relationships between the concentrations of soluble reactive
      phosphorus (SRP), TP, and chlorophyll a (Chl a) in bottom water and MBP in
      sediments. These relationships might be very complicated and need further
      exploration. This work is the first comprehensive study of the seasonal and
      spatial distribution of MBP in sediments and its relationships with environmental
      factors in a typical estuary, and will lead to deeper understanding of the
      phosphorus (P) biogeochemical cycle.

PMID- 18614182
TI  - Effects of fish farm waste on Posidonia oceanica meadows: synthesis and provision
      of monitoring and management tools.
AB  - This paper provides a synthesis of the EU project MedVeg addressing the fate of
      nutrients released from fish farming in the Mediterranean with particular focus
      on the endemic seagrass Posidonia oceanica habitat. The objectives were to
      identify the main drivers of seagrass decline linked to fish farming and to
      provide sensitive indicators of environmental change, which can be used for
      monitoring purposes. The sedimentation of waste particles in the farm vicinities
      emerges as the main driver of benthic deterioration, such as accumulation of
      organic matter, sediment anoxia as well as seagrass decline. The effects of fish
      farming on P. oceanica meadows are diverse and complex and detected through
      various metrics and indicators. A safety distance of 400 m is suggested for
      management of P. oceanica near fish farms followed by establishment of permanent
      seagrass plots revisited annually for monitoring the health of the meadows.

PMID- 18614183
TI  - Macrophages detoxify the genotoxic and cytotoxic effects of surgical cobalt
      chrome alloy particles but not quartz particles on human cells in vitro.
AB  - Particles of surgical cobalt chrome alloy are cytotoxic and genotoxic to human
      fibroblasts in vitro. In vivo orthopaedic patients are exposed to cobalt chrome
      particles as a result of wear of a joint replacement. Many of the wear debris
      particles that are produced are phagocytosed by macrophages that accumulate at
      the site of the worn implant and are disseminated to local and distant lymph
      nodes the liver and the spleen. In this study we have tested whether this process
      of phagocytosis could have altered the cytotoxic and genotoxic properties of the
      cobalt chrome particles. Quartz particles have been investigated as a control.
      Micron-sized particles of cobalt chrome alloy were internalised by either white
      cells of peripheral blood or by THP-1 monocytes for 1 week and 1 day,
      respectively. The particles were then extracted and presented at different doses
      to fibroblasts for 1 day. There was a reduction of the cytotoxicity and
      genotoxicity of the cobalt chrome particles after phagocytosis by white cells or
      THP-1 cells. Cobalt chrome particles that were internalised by fibroblasts also
      showed a reduction of their cytotoxicity but not their genotoxicity. In contrast
      the cytotoxicity and genotoxicity of quartz particles was increased after
      internalisation by THP-1 cells. The surface morphology of the cobalt chrome
      particles but not the quartz particles was changed after phagocytosis by THP-1
      cells. This study suggests that the genotoxic and cytotoxic properties of
      particles that fall within the size range for phagocytosis may be highly complex
      in vivo and depend on the combination of material type and previous phagocytosis.
      These results may have relevance for particle exposure from orthopaedic implants
      and from environmental or industrial pollution.

PMID- 18614184
TI  - Modelling human drug abuse and addiction with dedicated small animal positron
      emission tomography.
AB  - Drug addiction is a chronically relapsing brain disorder, which causes
      substantial harm to the addicted individual and society as a whole. Despite
      considerable research we still do not understand why some people appear
      particularly disposed to drug abuse and addiction, nor do we understand how
      frequently co-morbid brain disorders such as depression and attention-deficit
      hyperactivity disorder (ADHD) contribute causally to the emergence of addiction
      like behaviour. In recent years positron emission tomography (PET) has come of
      age as a translational neuroimaging technique in the study of drug addiction,
      ADHD and other psychopathological states in humans. PET provides unparalleled
      quantitative assessment of the spatial distribution of radiolabelled molecules in
      the brain and because it is non-invasive permits longitudinal assessment of
      physiological parameters such as binding potential in the same subject over
      extended periods of time. However, whilst there are a burgeoning number of human
      PET experiments in ADHD and drug addiction there is presently a paucity of PET
      imaging studies in animals despite enormous advances in our understanding of the
      neurobiology of these disorders based on sophisticated animal models. This
      article highlights recent examples of successful cross-species convergence of
      findings from PET studies in the context of drug addiction and ADHD and
      identifies how small animal PET can more effectively be used to model complex
      psychiatric disorders involving at their core impaired behavioural self-control.

PMID- 18614185
TI  - The effects of chronic ethanol administration on amygdala neuronal firing and
      ethanol withdrawal seizures.
AB  - Physical dependence on ethanol results in an ethanol withdrawal (ETX) syndrome
      including susceptibility to audiogenic seizures (AGS) in rodents after abrupt
      cessation of ethanol. Chronic ethanol administration and ETX induce functional
      changes of neurons in several brain regions, including the amygdala. Amygdala
      neurons are requisite elements of the neuronal network subserving AGS propagation
      during ETX induced by a subacute "binge" ethanol administration protocol.
      However, the effects of chronic ethanol administration on amygdala neuronal
      firing and ETX seizure behaviors are unknown. In the present study ethanol
      (5g/kg) was administered intragastrically in Sprague-Dawley rats once daily for
      28days [chronic intermittent ethanol (CIE) protocol]. One week later the rats
      began receiving ethanol intragastrically three times daily for 4days (binge
      protocol). Microwire electrodes were implanted prior to CIE or on the day after
      CIE ended to record extracellular action potentials in lateral amygdala (LAMG)
      neurons. The first dose of ethanol administered in the binge protocol following
      CIE treatment did not alter LAMG neuronal firing, which contrasts with firing
      suppression seen previously in the binge protocol alone. These data indicate that
      CIE induces neuroadaptive changes in the ETX network which reduce LAMG response
      to ethanol. LAMG neuronal responses to acoustic stimuli prior to AGS were
      significantly decreased during ETX as compared to those before ethanol treatment.
      LAMG neurons fired tonically throughout the tonic convulsions during AGS. CIE
      plus binge treatment resulted in a significantly greater mean seizure duration
      and a significantly elevated incidence of death than was seen previously with the
      binge protocol alone, indicating an elevated seizure severity following chronic
      ethanol administration.

PMID- 18614186
TI  - Delayed, context- and dopamine D1 receptor-dependent activation of ERK in
      morphine-sensitized mice.
AB  - Exposure to cues previously associated with intake of substances of abuse can
      promote drug related responses. In this study, we have examined the effect of
      exposure to a drug-associated context on the expression of morphine psychomotor
      sensitization. We show that sensitization is markedly increased in mice examined
      4 weeks after the last morphine injection. In addition, this incubation period
      confers to the environment paired with morphine the ability to increase ERK
      phosphorylation in the shell (but not the core) of the nucleus accumbens. Using
      transgenic mice with enhanced green fluorescent protein (EGFP) expression under
      the control of the dopamine D1 receptor (D1R) (Drd1a-EGFP) or D2 receptor
      promoter (Drd2-EGFP) we show that context-dependent ERK phosphorylation is
      restricted to D1R-expressing medium spiny neurons. Furthermore, this effect
      depends on D1R activation. These data show that, following repeated morphine
      injections, a drug-free period induces context-dependent phosphorylation of ERK
      in a specific population of neurons within the nucleus accumbens shell. This
      activation is associated to enhanced psychomotor sensitization and may be
      implicated in context-elicited drug seeking induced by repeated exposure to drugs
      of abuse.

PMID- 18614187
TI  - Hemispheric contribution to categorical and coordinate representational
      processes: a study on brain-damaged patients.
AB  - According to Kosslyn, two types of spatial relations can be used to arrange parts
      in mental imagery, i.e., categorical spatial relations and coordinate spatial
      relations, which are processed respectively by the left and right hemispheres. To
      investigate this possible hemispheric specialization in the imagery domain, we
      tested 34 left or right brain-damaged patients using both a categorical and a
      coordinate mental imagery task. The results show that left brain-damaged patients
      were selectively impaired on processing categorical representations, while right
      brain-damaged patients were more impaired on the processing the coordinate ones,
      regardless of the presence of visuo-spatial neglect. The present study partly
      support Kosslyn's theory and, despite data reported in previous studies of brain
      damaged patients, it also supports the hypothesis of a possible bilateral neural
      representation of mental imagery, with the two hemispheres taking part in this
      process in different ways.

PMID- 18614188
TI  - Xanthones with growth inhibition against HeLa cells from Garcinia
      xipshuanbannaensis.
AB  - Eight prenylated xanthones, bannaxanthones A-H (1-8), together with seven known
      compounds, were isolated from the acetone extract of the twigs of Garcinia
      xipshuanbannaensis. Their structures were elucidated by spectroscopic data
      interpretation. The cytotoxic activities of these compounds were evaluated using
      the MTT method. The results showed that xanthones with an unsaturated prenyl
      group had stronger cytotoxic activity against cancer cells, whereas those with
      hydroxylated prenyl groups had none.

PMID- 18614189
TI  - Plant cysteine proteinases: evaluation of the pharmacological activity.
AB  - Cysteine proteinases are involved in virtually every aspect of plant physiology
      and development. They play a role in development, senescence, programmed cell
      death, storage and mobilization of germinal proteins, and in response to various
      types of environmental stress. In this review, we focus on a group of plant
      defensive enzymes occurring in germinal tissue of Caricaceae. These enzymes
      elicit a protective response in the unripe fruit after physical stress. We
      propose that these enzymes follow a strategy similar to mammalian serine
      proteinases involved in blood clotting and wound healing. We show evidence for
      the pharmacological role of plant cysteine proteinases in mammalian wound
      healing, immunomodulation, digestive conditions, and neoplastic alterations.

PMID- 18614190
TI  - Acylated pregnane glycosides from Caralluma tuberculata and their antiparasitic
      activity.
AB  - Five pregnane glycosides were isolated from Caralluma tuberculata (1-5), in
      addition to a known one (russelioside E, 6). The structures of the isolated
      compounds were elucidated by the analysis of NMR data and FAB-MS experiments. All
      the isolated compounds were tested for their antimalarial and antitrypanosomal
      activities as well as their cytotoxicity against human diploid embryonic cell
      line (MRC5).

PMID- 18614191
TI  - Analysis of content about sexuality and human reproduction in school textbooks in
      Spain.
AB  - OBJECTIVES: The spread of sexually transmitted infections (STIs) inadolescents
      and teenage pregnancy rates are increasing. A decrease in the average age of
      youth's first sexual experience has also been noted. Sexual education programmes
      in schools have an important role to play in addressing these issues. The
      objective of this study was to analyse the content of textbooks in the areas of
      sexuality and human reproduction in order to evaluate the extent to which these
      textbooks promote healthy reproductive lifestyles, as well as avoidance of risk
      behaviour among adolescent students. STUDY DESIGN: Descriptive study of the
      content of school textbooks. METHODS: The study sample consisted of 12 textbooks
      (approximately 80% of all the textbooks used in Spanish secondary schools) which
      were edited in 2002. Content analysis evaluated the extent to which these books
      demonstrated reliable scientific information about: (a) condom effectiveness; (b)
      consequences, prevention and treatment of STIs; (c) family planning methods; (d)
      assisted reproductive technologies; and (e) the promotion of healthy reproductive
      lifestyles. RESULTS: All textbooks presented inaccurate information in the areas
      studied. One hundred and fifty one quotes were identified that facilitated
      incomplete perception of sexuality or risky behaviour. On average, 12.6 incorrect
      messages were identified in each textbook. CONCLUSIONS: The textbooks examined
      are neither appropriate nor sufficiently comprehensive for adolescent education
      on issues of sexuality. Results suggest a need for alternative textbooks based on
      better scientific evidence. It is essential that textbooks empower adolescents to
      make healthy decisions through the promotion of useful life skills that provide a
      more integrated concept of sexuality. There is a need for approaches to sexual
      education to integrate values commonly held by parents of the youth that use such
      texts.

PMID- 18614192
TI  - Potential role of ultra-sensitive estradiol assays in estimating the risk of
      breast cancer and fractures.
AB  - Radioimmunoassays (RIA) for the measurement of estradiol are sufficiently
      sensitive to assess the reproductive status of pre-menopausal women but lack
      sufficient sensitivity for low concentrations found in post-menopausal women.
      Bioassays have been used in the past to measure low estrogen levels but are
      impractical for handling high volumes of tests, particularly routine and non
      research specimens. In this study, we compared results for estradiol using
      several different methods including bioassay, RIA, and two tandem mass
      spectrometry methods. At the lower tertile of estradiol measurements by RIA, the
      overall excellent correlation with results obtained by tandem mass spectrometry
      (i.e. r=0.83) was lost (i.e. r=0.29). In addition, results were much lower with
      bioassay and mass spectrometry than with RIA suggesting that RIA measures
      undesired noise or estrogen metabolites. The mass spectrometry methods correlate
      best with isotopic kinetic methods when assessing aromatase inhibition. On this
      basis, we conclude that mass spectrometry assays are the best option for
      measurement of low estradiol concentrations. With such assays, greater
      discrimination should be achievable when using estradiol levels as a predictor of
      the risks for breast cancer and for fractures.

PMID- 18614193
TI  - RNA polymerase I-mediated expression of viral RNA for the rescue of infectious
      virulent and avirulent Rift Valley fever viruses.
AB  - Rift Valley fever virus (RVFV, Bunyaviridae, Phlebovirus) is a mosquito
      transmitted arbovirus that causes human and animal diseases in sub-Saharan Africa
      and was introduced into the Arabian Peninsula in 2000. Here, we describe a method
      of reverse genetics to recover infectious RVFV from transfected plasmids based on
      the use of the cellular RNA polymerase I promoter to synthesize viral
      transcripts. We compared its efficiency with a system using T7 RNA polymerase and
      found that both are equally efficient for the rescue of RVFV generating titers of
      approx. 10(7) to 10(8) pfu/ml. We used the RNA polymerase I-based system to
      rescue both attenuated MP12 and virulent ZH548 strains as well as chimeric MP12
      ZH548 viruses, and in addition RVFV expressing reporter proteins.

PMID- 18614195
TI  - Uptake rates of alkylphenols, PAHs and carbazoles in semipermeable membrane
      devices (SPMDs) and polar organic chemical integrative samplers (POCIS).
AB  - Passive sampling devices provide a useful contribution to the monitoring of
      contaminants in the aquatic environment. However, calibration data needed for the
      calculation of water concentrations from sampler accumulations are restricted to
      a limited number of compound classes. Thus uptake of a range of alkylated phenols
      (AP), polycyclic aromatic hydrocarbons (PAH) and carbazoles was determined for
      semipermeable membrane devices (SPMDs) and polar organic chemical integrative
      samplers (POCIS) using a flow through exposure system. Sampling rates ranged from
      0.02 to 0.26 l d(-1) for POCIS and 0.02 to 13.83 l d(-1) for SPMDs. Observed SPMD
      uptake was also compared to that predicted by an empirical model including the
      use of performance reference compounds (PRCs). Predicted sampling rates did not
      differ by more than a factor of 1.3 from experimental values for PAH, providing
      further evidence that the PRC approach can be successfully used to determine in
      situ sampling rates for these compounds. Experimental sampling rates for AP in
      SPMDs were, however, much lower than predicted. This discrepancy was too large to
      be explained by small uncertainties in the calibration system or in the
      calculations. Based on these data we conclude that while hydrophobic AP are
      accumulated by SPMDs their partitioning cannot be predicted from their logK(ow)
      using current methods. Due to this lower than expected uptake, sampling rates
      were only higher in SPMDs than POCIS in the range of logK(ow)>5.0. Simultaneous
      deployment of both sampler types allows the study of compounds with a broad range
      of physicochemical properties.

PMID- 18614196
TI  - Evaporative mass transfer behavior of a complex immiscible liquid.
AB  - A series of laboratory experiments was conducted with a multiple-component
      immiscible liquid, collected from the Picillo Farm Superfund Site in Rhode
      Island, to examine liquid-vapor mass-transfer behavior. The immiscible liquid,
      which comprises solvents, oils, pesticides, PCBs, paint sludges, explosives, and
      other compounds, was characterized using gas chromatography and gas
      chromatography/mass spectrometry to determine mole fractions of selected
      constituents. Batch experiments were conducted to evaluate equilibrium phase
      partitioning behavior. Two sets of air-stripping column studies were conducted to
      examine the mass-transfer dynamics of five selected target compounds present in
      the immiscible-liquid mixture. One set of column experiments was designed to
      represent a system with free-phase immiscible liquid present; the other was
      designed to represent a system with a residual phase of immiscible liquid.
      Initial elution behavior of all target components generally appeared to be ideal
      for both systems, as the initial vapor-phase concentrations were similar to vapor
      phase concentrations measured for the batch experiment and those estimated using
      Raoult's law (incorporating the immiscible-liquid composition data). Later-stage
      removal of 1,2-dichlorobenzene appeared to be rate limited for the columns
      containing free-phase immiscible liquid and no porous medium. Conversely,
      evaporative mass transfer appeared to be ideal throughout the experiment
      conducted with immiscible liquid distributed relatively uniformly as a residual
      phase within a sandy porous medium.

PMID- 18614194
TI  - Repression of human cytomegalovirus major immediate early gene expression by the
      cellular transcription factor CCAAT displacement protein.
AB  - Initiation of human cytomegalovirus (HCMV) productive infection is dependent on
      the major immediate early (MIE) genes ie1 and ie2. Several putative binding sites
      for CCAAT displacement protein (CDP or CUX1) were identified within the MIE
      promoter/regulatory region. Binding assays demonstrated binding of CUX1 to MIE
      region oligonucleotides containing the CUX1 core binding sequence ATCGAT and
      mutagenesis of this sequence abrogated CUX1 binding. Furthermore, CUX1 repressed
      expression of a luciferase reporter construct controlled by the MIE promoter, and
      mutation of CUX1 binding sites within the promoter diminished this repressive
      function of CUX1. In the context of virus infection of HEK293 cells transfected
      with the CUX1 expression vector, CUX1 showed evidence of association with the
      HCMV MIE regulatory region and inhibited the capacity of the virus to express ie1
      and ie2 transcripts, suggesting that this cellular factor regulates MIE gene
      expression following virus entry. These data identify a role for CUX1 in
      repressing HCMV gene expression essential for initiation of the replicative
      cycle.

PMID- 18614197
TI  - Toker cells of the breast. Morphological and immunohistochemical characterization
      of 40 cases.
AB  - Toker cells are epithelial cells with clear cytoplasm usually free of cytologic
      atypia localized within the nipple epidermis. Rarely, they can be so numerous and
      atypical as to require a careful distinction from malignant cells of Paget's
      disease. The purpose of this paper was to better define the prevalence of these
      atypical Toker cells and to investigate phenotypic markers that can be helpful in
      the differential diagnosis with Paget's disease. Forty cases containing Toker
      cells were identified in the nipples of 390 patients (10.2%) who underwent
      complete breast mastectomy. In 24 cases (60%), Toker cells were cytologically
      bland and benign, disappearing after a few consecutive sections ("normal Toker
      cells"). In 11 cases (27.5%), Toker cells were more numerous and persistent on
      serial sections, still retaining bland cytologic features ("hyperplastic Toker
      cells"). In 5 cases (12.5%), hyperplastic Toker cells also became cytologically
      atypical ("hyperplastic and atypical Toker cells"). On immunohistochemistry,
      Toker cells were positive for estrogen (25/25) and progesterone (20/23)
      receptors, and negative for CD138 (18/19) and p53 (14/14); some hyperplastic and
      atypical Toker cells (4 cases) and hyperplastic Toker cells (1 case) showed faint
      immunoreactivity for HER2/NEU. For comparison, Paget's disease were negative for
      estrogen (6/10) and progesterone (7/10) receptors, and positive for CD138 (7/10),
      p53 (6/10), and HER2/NEU (9/10). Both Toker cells and Paget's disease stained
      positive for cytokeratin 7 and epithelial membrane antigen, and negative for p63.
      In conclusion, Toker cells are detectable in 10% of the nipples and are usually
      cytologically bland, but in 10% of the cases they can be morphologically
      atypical. The combined use of CD138/p53 is very helpful in distinguishing these
      atypical Toker cells from those of Paget's disease.

PMID- 18614198
TI  - Primary diffuse large B-cell lymphomas of the bone: prognostic relevance of
      protein expression and clinical factors.
AB  - Diffuse large B-cell lymphomas can be considered primary bone tumors if they are
      monostotic or polyostotic, affecting multiple skeletal sites without visceral or
      lymph node involvement. They are rarely considered as extranodal lymphomas or as
      bone tumors, respectively. To elucidate the prognostic relevance of
      clinicopathologic characteristics in such disease, we collected a cohort of
      primary diffuse large B-cell lymphomas of the bone and retrospectively
      investigated 33 patients. The cohort encompassed the years 1975 to 2004. Protein
      expression patterns were identified by immunohistochemistry applied to a tissue
      microarray. The patients included 23 males (mean age, 37 years) and 10 females
      (mean age, 54 years). Disease stage was I and II in 30 and IV in 3 patients.
      Within the mean follow-up of 28 months, 6 patients died. Median overall survival
      was reached after 78 months. Clinical factors favoring a good prognosis were age
      younger than 53 and administration of chemotherapy. Of the phenotypic markers
      analyzed (CD10, CD44s, CD138, Bcl-2, Bcl-6, MUM1, and Ki-67), MUM1 expression in
      more than 10% of the tumor cells and CD10 expression in less than 55% as well as
      a nongerminal center signature substantiated adverse outcome in a univariate
      model. In summary, poor survival in PB-DLBCL was clearly predicted in patients
      older than 53, who had not received chemotherapy, and who demonstrated MUM1
      expression and nongerminal center phenotype.

PMID- 18614199
TI  - Elevated circulating fetal nucleated red blood cells and placental pathology in
      term infants who develop cerebral palsy.
AB  - An elevated circulating fetal nucleated red blood cell count has long been
      recognized as an indicator of significant intrauterine stress. However, the
      nature of the causative events and their timing remain controversial. In this
      study, subacute and chronic placental lesions known to be associated with
      neurodisability were used as surrogates for antenatal stress. Mother-infant pairs
      with complete blood counts within 2 hours of delivery (n = 81) were drawn from a
      larger database of 152 term infants with cerebral palsy. An elevated nucleated
      red blood cell count (2.5 x 10(3)/mm(3)) in these infants was associated with a
      significantly increased prevalence of subacute or chronic placental lesions,
      whereas clinical findings did not significantly differ. The number of nucleated
      red blood cells per 10 high-power fields of villous parenchyma was directly
      correlated with the nucleated red blood cell count, and a threshold of 10 or more
      nucleated red blood cells predicted a nucleated red blood cell count greater than
      2.5 x 10(3)/mm(3). Among individual placental lesions, multiple foci of avascular
      villi and chronic villitis were significantly associated with an elevated
      nucleated red blood cell count, whereas meconium-associated vascular necrosis
      showed a borderline association. Acute chorioamnionitis was the only placental
      lesion more common in the group without elevated nucleated red blood cell count.
      The presence of significant placental lesions was associated with an elevated
      nucleated red blood cell count in infants with or without either acidosis (cord
      pH <7.0) or birth asphyxia (American College of Obstetrics and Gynecology
      criteria). Acidosis and birth asphyxia were not significantly related to an
      elevated nucleated red blood cell count in infants without these placental
      lesions.

PMID- 18614200
TI  - Evaluation of 2 whole-slide imaging applications in dermatopathology.
AB  - Digitization of glass slides holds great promise for increasing workflow
      efficiency, but current applications have not gained widespread acceptance.
      Applications to date have not taken into consideration pathologists' workflow
      patterns, and as a result many find navigation cumbersome and interpretation more
      challenging when compared to glass slides. We observed 3 dermatopathologists
      evaluate a set of cases using 2 digital applications, one of which used a novel
      navigation method developed in-house. We then compared their approach to the
      digital slides with the gold standard traditional microscopy with glass slides.
      Common diagnoses were identified in 3 categories: inflammatory, nonmelanocytic,
      and melanocytic lesions. Forty-five cases were selected representing these
      diagnoses. Digital slides were captured on a commercially available scanner. Sign
      out was performed with a commercial viewer as well as with the in-house
      application. Sessions were captured on video and reviewed. Time to examine each
      slide, time spent at each magnification, and diagnostic concordance were
      measured. Average time spent per slide was least with the microscope (23 seconds)
      as compared with the in-house (34 seconds) or the vendor application (38
      seconds). This difference was most significant in the least complex cases.
      Pathologists reported difficulty interpreting mitotic figures, neutrophil
      lobules, and eosinophil granules by digital slides. These results suggest that
      current applications for viewing digital slides do not yet provide a more
      efficient means of evaluating dermatopathology cases and reinforce the need for
      improvement in both the capture process and the presentation of digital slides,
      with particular attention paid to the interface and navigation.

PMID- 18614202
TI  - Daily physicochemical, microbiological and ecotoxicological fluctuations of a
      hospital effluent according to technical and care activities.
AB  - The problem of hospital effluents falls into the framework of hazardous
      substances due to the specific substances used and discharged for the most part
      into urban drainage networks without prior treatment. This in-depth study has led
      to greater understanding of the effluents discharged by hospitals. The
      experimental program implemented consisted in carrying out parallel sampling of
      the effluents of one hospital: a 24 h-average sample and 5 periodic samples
      corresponding to fractions of times and hospital activities. The samples were
      characterized by physicochemical, microbiological and ecotoxicological analyses.
      The results highlight that the effluents contained very little bacterial flora
      and a moderate organic pollution. However, a numerous of specific pollutants were
      detected: AOX, glutaraldehyde, free chlorine, detergents, Freon 113 as well as
      alcohols, acetone, formaldehyde, acetaldehyde, ammonium, phenols and several
      metals. The battery of bioassays showed that the effluents had a high level of
      ecotoxicity partly linked to particles in suspension and, that pollution
      fluctuated greatly during the day in connection with hospital activities.
      Finally, the PNEC values compared to the concentrations of pollutants dosed in
      the effluents highlighted that their toxicity was mainly due to several major
      pollutants, in particular free chlorine. Some hypotheses require additional
      experiments to be carried out. They concern: reactions of fermentations likely to
      occur in the drainage network and to form secondary toxic compounds, retention of
      chlorine by particles and physicochemical characterization of suspended solids.

PMID- 18614201
TI  - Eosinophils and mast cells in chronic gastritis: possible implications in
      carcinogenesis.
AB  - Eosinophils and mast cells participate in the immune response against
      Helicobacter pylori, but their involvement in the gastric precancerous process is
      unclear. This study aimed to estimate eosinophil and mast cell density in antral
      mucosa in subjects from 2 Colombian populations with contrasting gastric cancer
      risks. Gastric mucosa biopsies were collected from 117 adult males (72 from a
      high-risk area and 45 from a low-risk area). A histopathology score was used to
      quantify severity of the lesions. Quantitation of eosinophils in hematoxylin
      eosin-stained sections and mast cells in immunostained sections for CD117/c-Kit
      was performed. Helicobacter pylori infection and genotyping were assessed in
      Steiner stain and polymerase chain reaction, respectively. Logistic regression
      models and semiparametric cubic smoothing splines were used for analysis of the
      results. Eosinophil density was significantly higher in subjects from the low
      risk area as compared with subjects from the high-risk area. In both populations,
      eosinophil density increased with the histopathology score in the progression of
      lesions from normal morphology to multifocal atrophic gastritis. Intestinal
      metaplasia and dysplasia specimens showed further increase in eosinophil density
      in the high-risk area but an abrupt decrease in the low-risk area. Mast cell
      density increased in parallel to the histopathology score in both populations.
      Our results suggest that eosinophils play a dual role in chronic gastritis. In
      the low-risk area, elevated eosinophil density represents a T helper 2-biased
      response that may down-regulate the effects of proinflammatory cytokines
      preventing cancer development. In contrast, in the high-risk area, eosinophils
      might promote a T helper 1-type response leading to progression of precancerous
      lesions.

PMID- 18614203
TI  - Application of the Spanish methodological approach for biosphere assessment to a
      generic high-level waste disposal site.
AB  - A methodological approach which includes conceptual developments, methodological
      aspects and software tools have been developed in the Spanish context, based on
      the BIOMASS "Reference Biospheres Methodology". The biosphere assessments have to
      be undertaken with the aim of demonstrating compliance with principles and
      regulations established to limit the possible radiological impact of radioactive
      waste disposals on human health and on the environment, and to ensure that future
      generations will not be exposed to higher radiation levels than those that would
      be acceptable today. The biosphere in the context of high-level waste disposal is
      defined as the collection of various radionuclide transfer pathways that may
      result in releases into the surface environment, transport within and between the
      biosphere receptors, exposure of humans and biota, and the doses/risks associated
      with such exposures. The assessments need to take into account the complexity of
      the biosphere, the nature of the radionuclides released and the long timescales
      considered. It is also necessary to make assumptions related to the habits and
      lifestyle of the exposed population, human activities in the long term and
      possible modifications of the biosphere. A summary on the Spanish methodological
      approach for biosphere assessment are presented here as well as its application
      in a Spanish generic case study. A reference scenario has been developed based on
      current conditions at a site located in Central-West Spain, to indicate the
      potential impact to the actual population. In addition, environmental change has
      been considered qualitatively through the use of interaction matrices and
      transition diagrams. Unit source terms of (36)Cl, (79)Se, (99)Tc, (129)I,
      (135)Cs, (226)Ra, (231)Pa, (238)U, (237)Np and (239)Pu have been taken. Two
      exposure groups of infants and adults have been chosen for dose calculations.
      Results are presented and their robustness is evaluated through the use of
      uncertainty and sensitivity analyses.

PMID- 18614204
TI  - The long pentraxin 3 and its role in autoimmunity.
AB  - OBJECTIVES: To review the physiological and physiopathological roles of pentraxin
      3 (PTX3), focusing on autoimmunity and vascular pathology. METHODS: A systematic
      literature review using the keywords "pentraxin 3," "innate immunity,"
      "apoptosis," "autoimmunity," and "endothelial dysfunction" from 1990 to 2007 was
      performed. All relevant articles and pertinent secondary references in English
      were reviewed. RESULTS: PTX3 has a large number of multiple functions in
      different contexts. PTX3 plays an important role in innate immunity,
      inflammation, vascular integrity, fertility, pregnancy, and also in the central
      nervous system. In innate immunity, its normal function is to increase the immune
      response to selected pathogens while also exerting control over potential
      autoimmune reactions. It maintains a tightly homeostatic equilibrium in the local
      immune microenvironment by avoiding an exaggerated immune response and
      controlling peripheral tolerance to self-antigens. In contrast, in some
      autoimmune diseases, PTX3 appears to be involved in the development of autoimmune
      phenomena. A possible explanation for these apparent paradoxical functions may be
      related to the highly polymorphic PTX3 gene. CONCLUSION: PTX3 is physiologically
      a protective molecule. However, in several autoimmune diseases PTX3 appears to
      facilitate the development of autoimmunity. The PTX3 gene could influence the
      development of autoimmune reactions and vascular involvement in human pathology.

PMID- 18614205
TI  - Prothrombotic changes with acute psychological stress: combined effect of
      hemoconcentration and genuine coagulation activation.
AB  - INTRODUCTION: Acute psychosocial stress accelerates blood coagulation and elicits
      hemoconcentration which mechanisms are implicated in acute coronary thrombotic
      events. We investigated the extent to which the change in prothrombotic measures
      with acute stress reflects hemoconcentration and genuine activation of
      coagulation. MATERIAL AND METHODS: Twenty-one middle-aged healthy men underwent
      three sessions of a combined speech and mental arithmetic task with one-week
      intervals. Coagulation and plasma volume were assessed at baseline, immediately
      post-stress, and 45 min post-stress at sessions one and three. Measures of both
      visits were aggregated to enhance robustness of individual biological stress
      responses. Changes in eight coagulation measures with and without adjustment for
      simultaneous plasma volume shift were compared. RESULTS: From baseline to
      immediately post-stress, unadjusted levels of fibrinogen (p=0.028), clotting
      factor VII activity (FVII:C) (p=0.001), FVIII:C (p<0.001), FXII:C (p<0.001), and
      von Willebrand factor (VWF) (p=0.008) all increased. Taking into account
      hemoconcentration, fibrinogen (p=0.020) and FVII:C levels (p=0.001) decreased,
      activated partial prothrombin time (APPT) shortened (p<0.001) and prothrombin
      time (PT) was prolonged (p<0.001). Between baseline and 45 min post-stress,
      unadjusted (p=0.050) and adjusted (p=0.001) FVIII:C levels increased, adjusted
      APTT was prolonged (p=0.017), and adjusted PT was shortened (p=0.033). D-dimer
      levels did not significantly change over time. CONCLUSIONS: Adjustment for stress
      hemoconcentration altered the course of unadjusted levels of several
      prothrombotic factors. After adjustment for hemoconcentration, APPT was shortened
      immediately post-stress, whereas 45 min post-stress, FVIII:C was increased and PT
      was shortened. Procoagulant changes to acute stress may reflect both
      hemoconcentration and genuine activation of coagulation molecules and pathways.

PMID- 18614206
TI  - Recent venous thromboembolism amongst adult individuals attending general
      practitioner ambulatory (the FAST study): prevalence of cardiovascular risk
      factors.

PMID- 18614207
TI  - Determination of nitric oxide synthase activity and apoptosis of germ cells in
      different obstruction models.
AB  - We aimed to determine the changes of inducible nitric oxide synthase (iNOS) and
      endothelial nitric oxide synthase (eNOS) immunoreactivity and apoptosis after
      proximal and distal obstruction models on ipsilateral and contralateral
      testicular tissues. Male albino Wistar rats were randomly divided into three
      groups (n=30): a control group which underwent sham operations (n=10), a
      unilateral vasal ligation (n=10) and a unilateral epididymal ligation group
      (n=10). iNOS and eNOS distribution and apoptosis were studied in both ipsilateral
      and contralateral testes using quantitative immunohistochemistry. Nitric oxide
      synthase activity was significantly affected in ipsilateral and contralateral
      testes cells after vasal and epididymal ligation. eNOS immunoreactivity increased
      markedly after ipsilateral vasal ligation (ILVL). Degeneration-related changes
      were also associated with changes in apoptotic rate. Analysis using the terminal
      dUTP nick end-labeling TUNEL method revealed that apoptotic cell numbers
      significantly increased after ILVL. p53 and bcl-2 immunoreactivity increased in
      both experimental groups compared with the sham-operated group. Changes in iNOS
      and eNOS immunolocalisation were strongly associated with cell damage, because
      germ cell degeneration was more prominent in the ILVL group. Altered p53
      immunolocalisation was also associated with cell degeneration, and a rise in bcl
      2 immunoreactivity might be considered to reflect a protective mechanism in the
      testis. These cellular changes could enlighten understanding of the interaction
      between testicular functioning and damage.

PMID- 18614208
TI  - Voltage-independent calcium influx in smooth muscle.
AB  - In smooth muscle cells, agonists such as neurotransmitters or hormones can induce
      an increase in [Ca(2+)](i) via a release of intracellular stored calcium or/and
      an influx of extracellular calcium. The calcium entry pathway operates through a
      variety of plasmalemmal calcium channels which involve voltage-dependent and
      voltage-independent calcium channels. Voltage-independent calcium channels
      include (1) receptor-operated channels (ROCs) activated by agonist-receptor
      interaction and, in the majority of cases, the downstream signal transduction
      proteins, (2) store-operated channels (SOCs) activated by the emptying of
      intracellular Ca(2+) store (mainly the sarcoplasmic reticulum), (3)
      mechanosensitive or stretch-activated channels (SACs) activated by membrane
      stretch. Generally, voltage-independent calcium channels are calcium permeable
      non-selective cation channels with electrophysiological differences, complex
      regulatory mechanisms and pharmacology. Although the molecular identity of
      voltage-independent calcium channels is not yet fully elucidated, there are
      growing evidences that these channels correspond to a new family of membrane
      proteins encoded by mammalian homologues of specific transient receptor potential
      (TRP) genes. Several types of TRP proteins are ubiquitously expressed in smooth
      muscle cells and variations in the expression depend on tissue and species. More
      recently, other proteins such as Orai1 and STIM1 proteins have been also proposed
      as participating in the molecular identity of voltage-independent calcium
      channels. These channels control phenomena such as smooth muscle cells
      proliferation and/or contraction.

PMID- 18614209
TI  - Re: Orbitozygomatic approach for excisions of orbital tumors with 1 piece of
      craniotomy bone flap: 2 case reports by Chi-Wen Chang et al. Surg Neurol
      2007;68(SI):58.

PMID- 18614210
TI  - Stereolithography in spine pathology: a 2-case report.
AB  - BACKGROUND: Solid plastic replicas of anatomical structures obtained by
      stereolithography from computed tomographic images and magnetic resonance imaging
      are being used as complementary tools for diagnostic purposes and therapy
      planning for diverse pathologies. CASE DESCRIPTIONS: Case 1--The spine mold of a
      62-year-old man with neurologic compromise secondary to degenerative cervical
      disease was used to study the pathologic features of his spine and to plan and
      simulate the approach to remove osteophytes before surgery. Also, by examining
      the replica of his spine, the unconvinced patient was able to understand the
      nature of his pathology and realize that his neurologic symptoms would disappear
      only through surgery, as they did. Case 2--A 27-year-old woman had uncontrolled
      back and leg pain possibly related to anxiety and depression. She had undergone
      one unsuccessful lumbo-sacral surgery and was now obsessed with the thought that
      her second surgery, performed by us, likewise had failed, even though her
      magnetic resonance images proved otherwise. It was not until she held a replica
      of her repaired spine in her hands that she was able to understand that her pain
      was unfounded. Once she was able to relax, her chronic pain and anxiety
      disappeared within a month, using the same antidepressive treatment that formerly
      had been ineffective. CONCLUSIONS: Spine replicas are useful devices for
      diagnosis, planning, and simulating surgery, and they enable patients to
      understand the nature of their pathologies and the surgical procedures at hand.

PMID- 18614211
TI  - Intracranial aneurysms in sickle cell patients: report of 2 cases and review of
      the literature.
AB  - BACKGROUND: The sickle cell disease has different neurologic complications,
      including cerebral aneurysms. This disease may lead to endothelial damage, which
      favors the development of cerebral aneurysms. Only a few cases demonstrated by
      cerebral angiography or surgery have been reported in the English literature
      referring to cerebral aneurysms in sickle cell patients. CASE DESCRIPTION: We
      report 2 patients with sickle cell disease whose cerebral aneurysms were
      successfully treated by open surgery. CONCLUSION: Sickle cell patients have a
      high occurrence of multiple aneurysms, and a high prevalence of posterior
      circulation aneurysms. This must be interpreted with caution, and further studies
      are needed to confirm this association.

PMID- 18614213
TI  - Re: Orbitozygomatic approach for excisions of orbital tumors with 1 piece of
      craniotomy bone flap: 2 case reports by Chi-Wen Chang et al. Surg Neurol
      2007;68(SI):58.

PMID- 18614214
TI  - Posterior fossa exploration in treatment of trigeminal neuralgia associated with
      multiple sclerosis.
AB  - BACKGROUND: The possible surgical options during PFE in treatment of TN in
      patients with MS are MVD and PSR. Only sporadic cases of PSR in treatment of TN
      patients with MS have been reported. METHODS: We retrospectively analyzed the
      outcome of surgical treatment in 8 patients with MS who underwent PFE due to
      surgical treatment of medically intractable TN. MVD was projected in severe
      neurovascular conflict, MVD + PSR in mild conflict, and PSR alone in cases
      without neurovascular conflict. RESULTS: There were no patients with severe
      neurovascular contact. In 5 patients with mild neurovascular contact and in 3
      without neurovascular contact, MVD + PSR and PSR alone were performed,
      respectively. An immediate BNI-score of I was achieved in all patients. There
      were 2 minor and 1 major recurrences. Nine years after surgery, 75% of the
      patients were free of pain. There was no immediate postoperative mortality.
      Postoperative cerebrospinal fluid rhinorrhea in 1 patient was resolved with
      spinal drainage. Two patients died during the follow-up period due to the
      complications of MS. CONCLUSION: In our experience, MVD + PSR or PSR alone are
      safe and effective surgical procedures in the management of TN complicating MS.
      In MVD + PSR patients, PSR seems to play more significant role than MVD in pain
      relief. Since there were not severe neurovascular conflicts in our patients with
      MS, MVD alone was never justified.

PMID- 18614215
TI  - RNA interference targeting EphA2 inhibits proliferation, induces apoptosis, and
      cooperates with cytotoxic drugs in human glioma cells.
AB  - BACKGROUND: Overexpression of EphA2 was detected in low- and high-grade glioma.
      To examine the role of EphA2 in human glioma cells, we studied its effects on
      proliferation and apoptosis using gene silencing through RNA interference.
      METHODS: One siRNA targeting EphA2 gene was synthesized in vitro and was
      transfected into the glioma U251n cells. Expression of EphA2 proteins was
      detected by Western blots and immunofluorescence. Cell apoptosis and
      mitochondrial membrane potential were analyzed by flow cytometry and annexin
      V/fluorescein isothiocyanate/propidium iodide, respectively. Caspase-3 activity
      was measured by a spectrofluorometer. MTT assay was used to examine changes in
      cell proliferation. RESULTS: After treatment with sequence-specific siRNA
      targeting EphA2, the protein level of the transfected group decreased
      significantly. As compared to non-siRNA transfected cells, the transfected group
      showed lower proliferation, higher apoptosis, and loss of mitochondrial membrane
      potential. Caspase-3 activity increased in cells treated with siRNA and
      downregulated when treated with caspase-3 inhibitor. And the effects were clearly
      additive when siRNA transfected cells treated with the anticancer agents.
      CONCLUSIONS: The results suggest that EphA2-siRNA inhibit U251n cell
      proliferation and induce their apoptosis. It is possible that EphA2 via
      mitochondrial and caspase-3 inhibits U251n cell apoptosis. And EphA2-siRNA
      transfection enhances U251n cells' sensitivity to chemotherapy. EphA2 may be an
      effective therapeutic target in patients with glioma. Silencing the receptor
      EphA2 gene is a novel approach for the containment of growth and migration of
      tumor in patients with malignant glioma.

PMID- 18614216
TI  - Hemodynamic changes in ipsi- and contralateral cerebral arterial territories
      after carotid endarterectomy using positron emission tomography.
AB  - BACKGROUND: The purpose of this study was to characterize ipsi- and contralateral
      cerebral hemodynamics before and after CEA. METHODS: Cerebral blood flow, CBV,
      and MVTT were measured in 10 patients before and after CEA using PET. Absolute
      and relative values of these parameters were calculated bilaterally for the
      entire arterial territories and hemispheres. RESULTS: For all territories in both
      hemispheres, the mean absolute postoperative CBF was significantly increased
      compared with preoperative CBF (P < .05). Only in MCA was this increase higher in
      the ipsilateral than in the contralateral hemisphere (P = .02). Cerebral blood
      volume was unaffected, whereas MVTT decreased in ipsilateral MCA (P = .05).
      CONCLUSIONS: The present findings suggest that, on the first day after CEA,
      absolute CBF is increased in all arterial territories on both ipsi- and
      contralateral sides, but that there are only minor changes in the relative
      distribution, whereas the CBV was unaffected.

PMID- 18614217
TI  - Allodynia corresponding to the levels of cervical cord injury treated by surgical
      decompression: a report of 3 cases.
AB  - BACKGROUND: The role and timing of surgical decompression for SCI remains
      controversial, when the surgical outcomes are evaluated only by neurologic
      recovery. Other than neurologic deficits, severe pain after SCI is a significant
      problem, deteriorating the patient's activity of daily living. In the present
      report, allodynia of patients' upper limbs caused by cervical SCI was treated
      successfully by surgical decompression. CASE DESCRIPTIONS: Three male patients
      received cervical SCI through minor accidents. They complained of allodynia and
      motor dysfunction at the spinal level compressed by preexisting lower cervical
      spondylosis, but they lacked symptoms or neurologic abnormalities below that
      spinal level. Severe pain was induced by soft touch or exposure to water at room
      temperature preoperatively. Surgical decompressions of the spinal cord and nerve
      roots were performed between 20 and 83 days (mean, 48.7 days) after the SCI.
      Allodynia was reduced in all patients immediately after surgery. Pain induced by
      soft touch disappeared within 4 days of operations, whereas pain by water
      exposure diminished within months. Recurrence of allodynia has not been observed
      in patients at least until the last follow-up, within periods ranging from 15 to
      39 months (average, 26 months). The mean preoperative VAS was 6.0, and this
      improved to 2.2 at 1 month and 0.8 at the final follow-up. CONCLUSION: We propose
      that patients with SCI with allodynia and motor dysfunction of the upper limbs
      related only to the compressed spinal levels are potentially treatable by
      surgical decompression.

PMID- 18614224
TI  - Blastocyst morphology, actin cytoskeleton quality and chromosome content are
      correlated with embryo quality in the pig.
AB  - Embryo survival rates obtained after transfer of in vitro produced porcine
      blastocysts are very poor. This is probably related to poor quality of the
      embryos. The aim of the present study was to determine markers for good quality
      blastocysts. Therefore, we tried to link blastocyst morphology to several
      morphological and cell biological properties, and evaluated the survival of in
      vitro produced, morphologically classified, blastocysts following non-surgical
      transfer. In vitro and in vivo produced blastocysts were allocated to two groups
      (classes A and B) on the basis of morphological characteristics. The quality of
      their actin cytoskeleton, their total cell number, their ability to re-expand
      after cytochalasin-B treatment and the occurrence of numerical chromosome
      aberrations were studied and compared. In vivo produced blastocysts were used as
      a control. Our results indicate that the ability of blastocysts to re-expand
      after cytochalasin-B-induced actin depolymerization was positively correlated
      with the morphology of the blastocyst, and associated with the quality of the
      actin cytoskeleton. Chromosome analysis revealed that mosaicism is inherent to
      the in vitro production of porcine embryos, but also that in vivo produced
      blastocysts contained some non-diploid cells. In non-surgical embryo transfer
      experiments more recipients receiving class A blastocysts were pregnant on Day 20
      than those receiving class B blastocysts. One recipient gave birth to six piglets
      from class A in vitro produced blastocysts, providing a verification of the
      enhanced viability of blastocysts that were scored as 'good' on the basis of
      their morphology.

PMID- 18614225
TI  - Effects of layering techniques on the micro-tensile bond strength to dentin in
      resin composite restorations.
AB  - OBJECTIVES: The purpose of this work was to investigate the effects of layering
      techniques in resin composite restorations on the micro-tensile bond strength to
      the dentin of the occlusal cavity. METHODS: Human premolars were extracted and
      randomly divided into four groups. The occlusal enamel was then removed to expose
      a flat superficial dentin surface. Cavities 3.5mm long and 3.5mm wide were
      prepared to a depth 3mm below the dentin surface. The adhesive Single Bond was
      applied according to the manufacturer's instructions. The teeth were then
      restored with Z100 resin composite as follows: Group 1 was restored in horizontal
      increments (three layers). Groups 2 and 3 were restored in different oblique
      increments (three layers). Group 4 was restored in oblique increments (four
      layers). After 24h storage at 37 degrees C in water, all the teeth were sectioned
      to obtain bar-shaped specimens with a bonded surface area of approximately 0.9 mm
      x 0.9 mm. Dentin micro-tensile bond strength was measured at a crosshead speed of
      0.5mm/min. The results obtained were statistically analyzed using one-way ANOVA
      and SNK test at a significance level of P=0.05. All fractures were then observed
      under a scanning electron microscope (SEM). RESULTS: The results showed that
      there is a significant difference between the strength of the micro-tensile bonds
      to the dentin of occlusal cavities depending on which of the four layering
      restorative techniques was used (P<0.01). SEM observation showed that failure
      patterns were most evidently interfacial cohesive failure. SIGNIFICANCE: Layering
      techniques in resin composite restorations affected the micro-tensile bond
      strength between the resin composite and the dentin. But the outcomes related to
      only Single Bond, as the same using other adhesives might have different
      outcomes.

PMID- 18614226
TI  - Polymerization shrinkage strain of interocclusal recording materials.
AB  - OBJECTIVES: The aim of this in vitro study was to investigate the polymerization
      shrinkage behavior and to measure the polymerization shrinkage-strain of
      interocclusal recording materials. METHODS: The materials investigated in this
      study were five polyvinylsiloxane (Imprint Bite, Silagum Automix Bite, O-Bite,
      Blu-Mousse Classic and Exabite II), one polyether (Ramitec) and one
      dimethacrylatebased (Luxabite) materials. The polymerization shrinkage values of
      ten specimens for each material were measured by the Bonded-disk method at 1, 3,
      5, 7 and 10 min after mixing at 37 degrees C. The amount of shrinkage-strain (%)
      was derived and all data were statistically analyzed by one-way ANOVA and the
      multiple comparison Scheffe test (alpha=0.05). RESULTS: The representative
      shrinkage-strain kinetic graphs showed that all specimens shrank immediately,
      except Luxabite which expanded for the initial few seconds. After that, the
      shrinkage-strain values increased in the magnitude up to 10 min, but its rate
      decreased gradually with time. The shrinkage-strain values (0.18+/-0.03-0.16+/
      0.03%) of O-Bite at 5, 7 and 10 min were significantly lower than the other
      materials, but Luxabite exhibited the highest values (3.10+/-0.17-3.30+/-0.16%).
      SIGNIFICANCE: The interocclusal recording materials investigated presented
      significantly different polymerization shrinkage-strain kinetics and showed
      dimensional changes even after the setting time indicated by respective
      manufacturers.

PMID- 18614227
TI  - The effect of platelet-rich plasma on healing in critical-size long-bone defects.
AB  - The role of platelet-rich plasma (PRP) as a promoter of bone healing remains
      controversial. The hypothesis investigated was that PRP improves bone healing of
      a critical-size diaphyseal radius defect in a rabbit model. The bone defect was
      filled with a high-surface ceramic scaffold, calcium-deficient hydroxyapatite
      (CDHA), with the addition of allogenic PRP, mesenchymal stem cells (MSC) or both.
      PRP yielded better bone formation than the empty CDHA scaffold as determined by
      both histology and micro-computer tomography (p<0.05) after 16 weeks, whereas no
      difference was observed on biomechanical testing. Similar behavior was found in
      samples with MSC; however, the combination of MSC and PRP did not further improve
      bone healing. Furthermore, the resorption of CDHA was improved by the addition of
      PRP, MSC and MSC/PRP, but there were no differences between the groups. The areas
      of bone formation were greater in areas adjacent to the bone resection areas and
      towards the intact ulna. In conclusion, PRP improves bone healing in a diaphyseal
      rabbit model on CDHA and the combination of CDHA. This study supports the
      allogenic use of PRP for bone healing as an off-the-shelf therapy.

PMID- 18614228
TI  - Regulation of cardiac Na+-Ca2+ exchanger activity by protein kinase
      phosphorylation--still a paradox?
AB  - The cardiac Na+-Ca2+ exchanger (NCX) is an important regulator of intracellular
      ion homeostasis and cardiac function. Gaining insight into modulation of the NCX
      is therefore important in order to understand ion handling in the heart under
      physiological and pathological conditions. Typically, the functional contribution
      of the NCX is often regarded as "secondary" to the changes in luminal Na+ and
      Ca2+. Whilst it is well accepted that the NCX can be regulated by various
      factors, including the concentrations of transported ions, direct receptor
      mediated modulation of the cardiac NCX is more controversial. Evidence from
      several different laboratories supports the notion that the cardiac NCX is a
      direct target of neurotransmitters and hormones and their downstream signalling
      pathways; however, the issue remains unresolved due to conflicting data showing a
      lack of direct modulation. The present review summarizes overall findings
      regarding the modulation of the cardiac NCX, in particular on molecular
      mechanisms of direct phosphorylation of NCX by beta-adrenergic/adenylate
      cyclase/protein kinase A and (for comparative purposes) on endothelin-1/protein
      kinase C signalling pathways. It also aims to consider whether it is currently
      possible to reconcile discrepancies between studies in the interpretation of the
      regulation of the cardiac NCX by agents stimulating the beta-adrenoceptor/PKA
      pathway.

PMID- 18614229
TI  - Bortezomib directly inhibits osteoclast function in multiple myeloma:
      implications into the management of myeloma bone disease.

PMID- 18614230
TI  - A pilot study of allogeneic cellular therapy for patients with advanced
      hematologic malignancies.
AB  - Allogeneic hematopoietic stem cell transplantation provides curative therapy for
      some patients with advanced hematologic malignancies. Disease response after
      allogeneic transplant is, at least in part, mediated by donor immune cells. In
      this report we describe a cellular therapy using haploidentical peripheral blood
      stem cells administered after very low dose total body irradiation (TBI)
      (100cGy). The donor cells were anticipated to be rejected, so no graft-versus
      host (GVHD) prophylaxis was used. Patients with persistent disease beyond 8 weeks
      could be further treated with infusions of irradiated haploidentical donor cells.
      Of the 10 patients enrolled in the study, durable engraftment of allogeneic cells
      was seen in one patient. Two patients with resistant relapsed acute myelogenous
      leukemia (AML) had a disease response. Analysis of T cell reactivity from one
      patient who achieved a complete response but did not have durable engraftment of
      donor cells indicated that disease response was associated with the generation of
      host-derived anti-leukemic cytotoxic CD8+ T cells that reacted with an AML
      associated proteinase 3 epitope. Results from this patient suggest that
      allogeneic therapy induced a host anti-tumor response associated with cytotoxic T
      cells reactive with a low affinity self-antigen.

PMID- 18614232
TI  - Assimilation and physiological effects of ferrocyanide on weeping willows.
AB  - Uptake, assimilation, and toxicity of exogenous iron cyanide complexes in plants
      were investigated. Pre-rooted young weeping willows (Salix babylonica L.) were
      exposed to hydroponic solutions spiked with potassium ferrocyanide at 24.0 +/- 1
      degrees C for 192 h. Transpiration rates, chlorophyll contents, soluble protein,
      and activities of superoxide dismutases (SOD), catalase (CAT), and peroxidase
      (POD) of the plants were monitored to determine toxicity to the cuttings. Of all
      selected parameters, POD activity in leaves was the most sensitive bioindicator
      to the increase of ferrocyanide concentrations. Between 11% and 19% of applied
      ferrocyanide in the solutions was removed by willows at the end of the incubation
      period. Only small amounts of ferrocyanide were recovered in different parts of
      the plant materials. Mass balance analysis showed that more than 90% of the
      ferrocyanide taken up from the hydroponic solutions was assimilated by plants.
      The assimilation of ferrocyanide by plants showed a dose-dependent manner. These
      findings suggest that phytoremediation of ferrocyanide-contaminating wastewater
      and soils can be possible for the environmental cleaning up.

PMID- 18614231
TI  - A population-based study of childhood sexual contact in China: prevalence and
      long-term consequences.
AB  - OBJECTIVES: This study provides national estimates of the prevalence of childhood
      sexual contact and its association with sexual well-being and psychological
      distress among adults in China. METHOD: A national stratified probability sample
      of 1,519 women and 1,475 men aged 20-64 years in urban China completed a computer
      administered survey in 1999-2000. The data from this survey on both adult-to
      child and peer-to-peer sexual contact before age 14 were subjected to descriptive
      and multivariate analyses that were adjusted for both sampling weights and
      sampling design. RESULTS: The overall prevalence of reported childhood sexual
      contact was 4.2%, with prevalence higher among men (5.1%) than among women (3.3%)
      and higher among those aged 20-29 years (8.3%). Childhood sexual contact was
      associated with multiplex consequences, including hyper-sexuality (high levels of
      masturbation, thoughts about sex, varieties of sexual practices, partner
      turnover), adult sexual victimization (unwanted sex, unwanted sexual acts, sexual
      harassment), sexual difficulties (genitor-urinary symptoms, sexually transmitted
      infections, sexual dysfunctions), and psychological distress. Psychological
      distress was largely mediated by adult sexual victimization, sexual difficulties,
      and hyper-sexuality. CONCLUSIONS: Despite the relatively modest prevalence of
      childhood sexual contact among Chinese adults, the association with multiplex
      adult outcomes suggests that much as in the West early sexual contact is a
      significant issue. PRACTICE IMPLICATIONS: The findings underscore the importance
      of public education about childhood sexual contact and abuse in China. The
      findings suggest a need for public health campaigns that tackle the stigma
      associated with being abused and encourage victims to report abusive behavior to
      proper sources. The findings are also consistent with new efforts to alleviate
      the negative long-term impact of childhood sexual abuse.

PMID- 18614233
TI  - The kappa immunoglobulin light chain repertoire of peripheral blood B cells in
      patients with juvenile rheumatoid arthritis.
AB  - The frequent appearance of antinuclear antibodies in patients with juvenile
      rheumatoid arthritis (JRA) indicates a loss of tolerance in B cell
      differentiation and/or activation. In this analysis, we were interested whether
      particular changes in the immunoglobulin light chain repertoire might exist in
      early-onset pauciarticular arthritis (EOPA) patients thereby potentially
      revealing distinct molecular patterns, which characterize defects in central
      tolerance mechanisms as well as an autoreactive peripheral B cell repertoire.
      Using single cell sorting and single cell PCR the distribution of Vkappa Jkappa
      rearrangements has been analyzed in individual naive B cells of patients with
      EOPA-JRA and healthy individuals. The immunoglobulin kappa light chain repertoire
      of peripheral blood B cells in EOPA patients seems to be skewed to a decreased
      use of downstream Vkappa gene segments indicating increased events of secondary
      V(D)J-recombination. Another prominent molecular pattern in JRA B cells seem to
      be a restricted combination of Vkappa Jkappa rearrangements based on the
      predominant utilization of the Jkappa 1 and 2 gene segment. The current study
      indicates disturbances in the peripheral B cell pool in juvenile rheumatoid
      arthritis. The peripheral blood B cell pool of JRA patients did show molecular
      changes in the kappa light chain repertoire which, in part, could be a sequel of
      secondary V(D)J-recombination and of a molecular bias during immunoglobulin
      rearrangement in the bone marrow. Thus, B cell tolerance might be broken by more
      than one pathogenic mechanism.

PMID- 18614234
TI  - Analysis and improvements to Kabat and structurally correct numbering of antibody
      variable domains.
AB  - In analysing protein sequence and structure, standardized numbering schemes allow
      comparison of features without explicit alignment. This has proved particularly
      valuable in the case of antibodies. The most widely used schemes (Kabat: sequence
      based; Chothia: structure-based) differ only in the numbering of the
      complementarity determining regions (CDRs). We have analyzed the numbered
      annotations in the widely used Kabat database and found that approximately 10% of
      entries contain errors or inconsistencies. Further analysis of sequence
      alignments in the context of structure suggest that the sites of the insertions
      in some framework regions in the Kabat and Chothia schemes are incorrect. We
      therefore propose a corrected version of the Chothia scheme which is structurally
      correct throughout the CDRs and frameworks. To perform this analysis, we have
      developed, and made available, a tool for the automatic application of Kabat,
      Chothia and modified-Chothia numbering schemes and have carefully benchmarked the
      performance of this tool.

PMID- 18614235
TI  - VHH, bivalent domains and chimeric Heavy chain-only antibodies with high
      neutralizing efficacy for scorpion toxin AahI'.
AB  - Many efforts aim at solving the serious problems encountered with immunotherapy
      against scorpion envenoming. The most attractive approach consists in generating
      single-chain antibody fragments (scFv) as their pharmaco-kinetic properties
      should match closely those of the scorpion toxins. Although high affinity scFv
      reagents have been generated in the past, their production level, stability, and
      toxin neutralizing capacity remain disappointingly poor. In the current study, we
      identified one Nanobody (Nb), a single-domain antigen-binding fragment of a
      dromedary Heavy-chain antibody (HCAb) that recognizes specifically the
      Androctonus australis hector AahI' toxin. This Nb has excellent production,
      stability and solubility characteristics. With this Nb we further manufactured a
      tandem linked bivalent construct and assembled a HCAb with improved antigen
      binding due to avidity effects. All these constructs were shown in mouse models
      to possess a scorpion toxin neutralization capacity that exceeds by far all
      previous attempts with scFv-based materials, even when used at lower doses. It is
      therefore clear that in the near future Nanobodies will be at the core of novel
      serotherapeutics as they combine multiple benefits over other reagents to treat
      scorpion envenomed patients.

PMID- 18614236
TI  - Characterisation of cathelicidin gene family members in divergent fish species.
AB  - Cathelicidins are antimicrobial peptides, well studied in mammals and found to be
      multifunctional proteins, important in the fight against bacterial invasion.
      Cathelicidins in fish have only recently been identified and little is known
      about their function and importance in the immune system of fish. In this study
      we have identified several novel cathelicidin proteins in far related fish
      species such as Atlantic cod (Gadus morhua) and Arctic charr (Salvelinus
      alpinus). Atlantic cod was found to have at least three cathelicidin genes of
      which two are nearly identical except for a nine-amino acid duplication in the
      antimicrobial peptide region. The predicted mature peptides of cod were found to
      be unusual peptides, made mainly of arginine, glycine and serine (RGS) residues
      and form a novel class of antimicrobial peptides. Cathelicidin in Arctic charr
      and brook trout (Salvelinus fontinalis) were found to have an exon deletion in
      the cathelin region of the protein, which would lead to the deletion of the
      predicted loop 2 of cathelin and its adjacent beta-strands. This is the first
      report of a deletion of a whole exon in the family of the cathelicidins.
      Infection of fish with pathogenic bacteria caused an upregulation of the
      expression of the cathelicidins in Arctic charr and Atlantic cod and indicates a
      role of these proteins in fish innate immunity.

PMID- 18614237
TI  - The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of
      dephosphorylating the TCR ITAMs and regulating NF-kappaB, is dispensable for T
      cell development and/or T cell effector functions.
AB  - T cell receptor signaling processes are controlled by the integrated actions of
      families of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases
      (PTPases). Several distinct cytosolic protein tyrosine phosphatases have been
      described that are able to negatively regulate TCR signaling pathways, including
      SHP-1, SHP-2, PTPH1, and PEP. Using PTPase substrate-trapping mutants and wild
      type enzymes, we determined that PTPN4/PTP-MEG1, a PTPH1-family member, could
      complex and dephosphorylate the ITAMs of the TCR zeta subunit. In addition, the
      substrate-trapping derivative augmented basal and TCR-induced activation of NF
      kappaB in T cells. To characterize the contribution of this PTPase in T cells, we
      developed PTPN4-deficient mice. T cell development and TCR signaling events were
      comparable between wild type and PTPN4-deficient animals. The magnitude and
      duration of TCR-regulated ITAM phosphorylation, as well as overall protein
      phosphorylation, was unaltered in the absence of PTPN4. Finally, Th1- and Th2
      derived cytokines and in vivo immune responses to Listeria monocytogenes were
      equivalent between wild type and PTPN4-deficient mice. These findings suggest
      that additional PTPases are involved in controlling ITAM phosphorylations.

PMID- 18614238
TI  - Synthesis, characterization, X-ray structure and in vitro antimycobacterial and
      antitumoral activities of Ru(II) phosphine/diimine complexes containing the
      "SpymMe2" ligand, SpymMe2=4,6-dimethyl-2-mercaptopyrimidine.
AB  - The reaction of cis-[RuCl(2)(dppb)(N-N)], dppb=1,4-bis(diphenylphosphino)butane,
      complexes with the ligand HSpymMe(2), 4,6-dimethyl-2-mercaptopyrimidine, yielded
      the cationic complexes [Ru(SpymMe(2))(dppb)(N-N)]PF(6), N-N=bipy (1) and Me-bipy
      (2), bipy=2,2'-bipyridine and Me-bipy=4,4'-dimethyl-2,2'-bipyridine, which were
      characterized by spectroscopic and electrochemical techniques and X-ray
      crystallography and elemental analysis. Additionally, preliminary in vitro tests
      for antimycobacterial activity against Mycobacterium tuberculosis H37Rv ATCC
      27264 and antitumor activity against the MDA-MB-231 human breast tumor cell line
      were carried out on the new complexes and also on the precursors cis
      [RuCl(2)(dppb)(N-N)], N-N=bipy (3) and Me-bipy (4) and the free ligands dppb,
      bipy, Me-bipy and SpymMe(2). The minimal inhibitory concentration (MIC) of
      compounds needed to kill 90% of mycobacterial cells and the IC(50) values for the
      antitumor activity were determined. Compounds 1-4 exhibited good in vitro
      activity against M. tuberculosis, with MIC values ranging between 0.78 and
      6.25microg/mL, compared to the free ligands (MIC of 25 to >50microg/mL) and the
      drugs used to treat tuberculosis. Complexes 1 and 2 also showed promising
      antitumor activity, with IC(50) values of 0.46+/-0.02 and 0.43+/-0.08microM,
      respectively, against MDA-MB-231 breast tumor cells.

PMID- 18614239
TI  - Data mining of metal ion environments present in protein structures.
AB  - Analysis of metal-protein interaction distances, coordination numbers, B-factors
      (displacement parameters), and occupancies of metal-binding sites in protein
      structures determined by X-ray crystallography and deposited in the PDB shows
      many unusual values and unexpected correlations. By measuring the frequency of
      each amino acid in metal ion-binding sites, the positive or negative preferences
      of each residue for each type of cation were identified. Our approach may be used
      for fast identification of metal-binding structural motifs that cannot be
      identified on the basis of sequence similarity alone. The analysis compares data
      derived separately from high and medium-resolution structures from the PDB with
      those from very high-resolution small-molecule structures in the Cambridge
      Structural Database (CSD). For high-resolution protein structures, the
      distribution of metal-protein or metal-water interaction distances agrees quite
      well with data from CSD, but the distribution is unrealistically wide for medium
      (2.0-2.5A) resolution data. Our analysis of cation B-factors versus average B
      factors of atoms in the cation environment reveals substantial numbers of
      structures contain either an incorrect metal ion assignment or an unusual
      coordination pattern. Correlation between data resolution and completeness of the
      metal coordination spheres is also found.

PMID- 18614240
TI  - Depression and anxiety through pregnancy and the early postpartum: an examination
      of prospective relationships.
AB  - BACKGROUND: The aim of this study was to explore the prospective relationship
      between depressive symptoms and anxiety across pregnancy and the early
      postpartum. METHODS: Participants (N=207) completed the State-Trait Anxiety
      Inventory Trait subscale, Beck Depression Inventory, and social support and sleep
      quality measures at two time points during pregnancy and once in the early
      postpartum period. RESULTS: After accounting for the relative stability of
      anxiety and depression over time, depressive symptoms earlier in pregnancy
      predicted higher levels of anxiety in late pregnancy and anxiety in late
      pregnancy predicted higher depressive symptomatology in the early postpartum. A
      bi-directional model of depression and anxiety in pregnancy was supported.
      LIMITATIONS: Data were based on self-reports and participating women were
      predominantly tertiary educated with high family incomes. CONCLUSION: Our
      findings suggest that depressive symptoms precede the development of higher
      levels of anxiety and that anxiety, even at non-clinical levels, can predict
      higher depressive symptoms. Clinicians are advised to screen for anxiety and
      depression concurrently during pregnancy.

PMID- 18614242
TI  - The impact of tonsillectomy with or without adenoidectomy on speech and voice.
AB  - OBJECTIVES: The aim of this study was to evaluate changes in acoustic features of
      speech and voice after tonsillectomy with or without adenoidectomy. METHODS:
      Before and 1 month after surgery the following parameters were estimated: average
      of fundamental frequency (Fo), Jitter percent (Jitt), Shimmer, noise-to-harmonics
      ratio (NHR), voice turbulence index (VTI), soft phonation index (SPI), degree of
      voiceless (DUV), degree of voice breaks (DVB) and peak amplitude variation (vAm);
      as an evaluation of nasal resonance, speech articulation and voice handicap index
      (VHI). RESULTS: The results were statistically evaluated using the unpaired t
      test. Probability values below 0.05 were regarded as significant. One month after
      surgery, our data showed significant (P<0.05) improvements of the acoustic and
      other parameters in the children submitted to adenotonsillectomy: Fo (176Hz vs.
      206Hz, after sustained vowels: 206Hz vs. 192Hz; 148Hz vs. 168Hz; 171Hz vs. 161Hz
      after balanced sentences), Jitt (0.85% vs. 1.81% to 0.82% vs. 1.81%), Shimmer
      (3.41% vs. 5.81% to 4.89% vs. 5.73%), NHR (0.16 vs. 0.42 to 0.29 vs. 0.39), VTI
      (0.05 vs. 0.38 to 0.28 vs. 0.37), SPI (14.78 vs. 21.14-19.89 vs. 21.89), DUV (0%
      vs. 0.44% to 0% vs. 0.48%), DVB (0% vs. 0.42% to 0% vs. 0.42%) and vAm (8.93% vs.
      23.89% to 8.89% vs. 24.25%). CONCLUSIONS: The results suggest the role of
      adenotonsillectomy in the improvement of voice and speech quality and of
      objective evaluation of speech and voice in the correct management of these
      children.

PMID- 18614241
TI  - The comparative validity of screening scales for postnatal common mental disorder
      in Kintampo, Ghana.
AB  - BACKGROUND: There have been few attempts formally to validate screening measures
      for postnatal common mental disorder in low income country settings. We have
      investigated the comparative validity of three different screening approaches in
      a community-based study in Kintampo, Ghana. METHOD: 160 women aged 15-45 years,
      and 5-11 weeks postpartum were first screened using the Self-Report Questionnaire
      (SRQ-20), with oversampling of higher scorers. The other test assessments were
      the Edinburgh Postnatal Depression Scale (EPDS) and the Patient Health
      Questionnaire (PHQ-9). Criterion validity was measured against the Comprehensive
      Psychopathological Rating Scale (CPRS), and concurrent validity against the WHO
      Disability Assessment Schedule. A sub-sample (n=40) was re-interviewed 2 weeks
      later for test-retest reliability. RESULTS: Internal consistency (Cronbach's
      Alpha) was equivalent across all three test scales; EPDS (0.79), SRQ-20 (0.78)
      and PHQ-9 (0.79). Test-retest reliability was better for PHQ-9 (ICC 0.75) than
      for the EPDS (0.51). For criterion validity the PHQ-9 (AUROC 0.90 (0.81-0.98)),
      was superior to the SRQ-20 (0.74 (0.62-0.86)) and the EPDS ((0.84 (0.76-0.92).
      Youden's Index was also superior for PHQ-9. Item analysis revealed that a mixture
      of somatic and cognitive symptoms best discriminated between cases and non-cases
      for all three scales. LIMITATIONS: Inability to ascertain inter-rater
      reliability, order effects and possible loss of technical equivalence due to item
      modifications. CONCLUSIONS: The evidence for the validity, reliability, and
      superiority of the PHQ-9 over other screening assessments has been extended. The
      PHQ-9 is short, easy to administer and acceptable to a largely illiterate
      population of Ghanaian women, 5 to 11 weeks post partum.

PMID- 18614243
TI  - A note on age-related comorbidity.
AB  - A few years ago a link was found between age-related maculopathy and senile
      dementia. A pointer to this might have been provided prospectively by a
      comparison of the partial correlation of the respective age-related prevalences.
      Here the question is asked whether this was an isolated example or whether it can
      be confirmed in a statistically significant number of comparisons. Published data
      on age-related prevalences of 15 conditions have been partially correlated in
      order to determine whether their correlations, if any, persist when the variable
      of age has been eliminated. This was the case in a significant fraction of the
      data, and, for a smaller, but still significant, fraction it was possible to find
      retrospective confirmatory evidence. The approach is held to provide a short-cut
      method for exploring possible, hitherto unestablished, links between existing
      studies, which, in turn, may lead to a better understanding of the nosology
      underlying them.

PMID- 18614244
TI  - The Biomaterialbank of the German Competence Network of Heart Failure (CNHF) is a
      valuable resource for biomedical and genetic research.
AB  - Genetic research on heart failure (HF) requires large cohorts of well-phenotyped
      patients. The German Competence Network of Heart Failure (CNHF) organized a
      biobank in 2004 to supply the necessary infrastructure and standard operating
      procedures (SOPs) for a centralized collection of blood specimen. We centralized
      data and collected serum, plasma and DNA of well characterized HF subjects all
      over Germany. Different pseudonyms were created automatically to address data
      safety and other concerns about privacy. Thus far, we have collected 85,000
      sample specimen from 9,500 prospectively evaluated patients with HF. Detailed
      medical data were prospectively acquired together with corresponding blood
      samples. In 2008 clinician-scientists can apply for access to the material. Our
      biobank represents a major facet of the CNHF and has already documented research
      and clinical utility.

PMID- 18614245
TI  - Left ventricular wall motion abnormality and myocardial dysfunction in stress
      cardiomyopathy: new pathophysiological aspects suggested by echocardiography.
AB  - We present our observations on 2 cases of stress cardiomyopathy in which, for the
      first time, wall motion and myocardial deformation analysis were performed by 2D
      strain imaging. Strikingly, in both patients, serial 2D-strain wall motion
      analysis revealed always synergic and synchronic longitudinal strain and strain
      rate patterns, even during the acute stress-induced episodes of left ventricular
      (LV) dysfunction, indicating uniform myocardial shortening, despite akinetic
      appearance of the LV apex in both conventional echocardiography and
      ventriculography. Another important observation was that during the acute stress
      induced episodes of severe LV dysfunction the end-systolic LV circumferential
      wall stress became in both patients several times higher in apical regions than
      at the LV base. These data suggest that the akinetic appearance of the apex can
      be related to the high systolic circumferential wall stress in this region, which
      opposes circumferential fiber shortening and thus apical akinesia and ballooning
      could be mainly the consequences of LV geometry-induced regional differences in
      wall stress, rather than a result of severely impaired myocardial contractility
      in apical regions.

PMID- 18614246
TI  - An accordion phenomenon with ST-segment elevation of electrocardiogram and
      anginal chest pain: a case report.
AB  - Tortuous coronary arteries frequently make percutaneous coronary intervention
      (PCI) difficult by causing less accessibility of guidewire toward the target
      lesion. After guidewire has been passed through the target lesion, it often
      assists a balloon catheter and stent system insertion along the stiff guidewire.
      However, artificial kinking and wrinkling might induce pseudo-narrowing of
      coronary arteries, which has been recognized as an "accordion phenomenon." We
      describe an educational case of an accordion phenomenon with ST-segment elevation
      of electrocardiogram and anginal chest pain when the stiff guidewire which had
      been withdrawn was advanced again into the distal site after deploying stents.

PMID- 18614247
TI  - Initial echocardiographic characteristics of pericardial effusion determine the
      pericardial complications.
AB  - BACKGROUND: Clinical implications of the initial echocardiographic
      characteristics of pericardial effusion (PE) have not been clearly demonstrated.
      We sought to evaluate the clinical significance of echogenic materials in PE.
      METHODS: Echocardiographic evaluation was performed in consecutive 178 patients
      with moderate to severe PE, and the etiology of PE was determined by clinical and
      pathologic studies. Echocardiography was repeated for 46 +/- 56 weeks. RESULTS:
      Echo-free PE was shown in 142 patients (80%, group A), while echogenic PE was
      found in 36 patients (20%, group B). In group B, intrapericardial fibrinous
      strands and/or exudative frond-like materials were detected in 29 patients and
      diffuse echogenic PE was shown in 7 patients. The prevalence of echogenic PE was
      the highest in tuberculosis (56.3%). All 49 patients with uremia or congestive
      heart failure showed clear echo-free PE. During the follow-up, the incidence of
      constrictive pericarditis and recurrent PE were highest in malignancy (38.6%) and
      tuberculosis (31.3%), respectively. The incidence of constrictive pericarditis
      (3.5 vs. 27.8%, p < 0.001) and recurrent PE (9.2 vs. 22.2%, p < 0.05) were
      significantly lower in group A than group B. The echogenic PE was the major
      independent predictor of the events by multiple stepwise logistic regression
      analysis (p < 0.01), regardless of the PE etiology. CONCLUSION: Echogenic
      materials in PE predict pericardial complications such as recurrence and
      constrictive pericarditis, irrespective of underlying diseases.

PMID- 18614248
TI  - Alcohol consumption and risk of coronary heart disease among Chinese men.
AB  - BACKGROUND: Observational studies suggest that moderate alcohol consumption may
      lower risk of myocardial infarction (MI) and coronary heart disease (CHD); yet,
      evidence for this comes almost entirely from Western populations. METHODS: We
      conducted a prospective cohort study in 64,597 Chinese men aged > or = 40 years
      who were free of clinical CHD at baseline examination. Data on frequency and type
      of alcohol consumed were collected at the baseline examination in 1991 using a
      standard protocol. Follow-up evaluation was conducted in 1999-2000, with a
      response rate of 94%. RESULTS: Over 494,084 person-years of follow-up, we
      documented 725 (361 fatal) incident MI and 976 (588 fatal) incident CHD events.
      After stratification by province to account for multi-stage sampling design and
      adjustment for age, education, physical activity, cigarette smoking, body mass
      index, systolic blood pressure, urbanization (urban vs. rural), geographic
      variation (north vs. south) and history of diabetes, relative risk (95%
      confidence interval) of MI was 0.93 (0.70-1.24) for participants consuming 1 to 6
      drinks/week, 0.66 (0.54-0.82) for those consuming 7 to 34 drinks/week, and 0.58
      (0.41-0.81) for those consuming > or = 35 drinks/week (p for linear trend
      <0.0001) compared to non-drinkers. The corresponding relative risks for CHD
      events were 0.99 (0.77-1.27), 0.67 (0.56-0.81), and 0.58 (0.44-0.78),
      respectively (p for linear trend <0.0001). CONCLUSION: Alcohol consumption may be
      related to lower risk of MI and CHD in middle-aged and older Chinese men.
      However, heavy alcohol consumption may lead to increased mortality from other
      causes; therefore, the implications of these findings should be interpreted
      cautiously.

PMID- 18614249
TI  - Coronary saddle embolism causing myocardial infarction in a patient with
      mechanical mitral valve prosthesis: treatment with thrombolytic therapy.
AB  - Coronary embolism is an uncommon cause for myocardial infarction in clinical
      practice and there is no consensus on the treatment of this subject. Thrombolytic
      agents and percutaneous intervention are up to date options and yet there are
      only a few case reports regarding thrombolytic therapy in this special subgroup
      of patients suffering from myocardial infarction. We reported a 37-year-old woman
      patient with non-ST elevation myocardial infarction due to coronary embolism who
      was successfully treated using intravenous thrombolytic therapy with tissue
      plasminogen activator.

PMID- 18614250
TI  - Association of plasma level of malondialdehyde-modified low-density lipoprotein
      with coronary plaque morphology in patients with coronary spastic angina:
      implication of acute coronary events.
AB  - BACKGROUND: Focal vasospasm is reportedly involved in a high incidence of acute
      coronary syndrome (ACS) as compared with diffuse vasospasm. No adequate studies
      have been conducted on the mechanism underlying the higher incidence of ACS
      involving focal vasospasm than of those involving diffuse vasospasm in patients
      with coronary spastic angina. METHODS AND RESULTS: Blood samples were collected
      from the aortic root (Ao) and the coronary sinus (CS) before provoking left
      coronary vasospasm using intracoronary administration of acetylcholine. After
      relief of vasospasm, volumetric analyses of vasospastic lesions were evaluated
      with 3-dimensional intravascular ultrasound in 64 patients. The percent plaque
      volume was more prominent in focal (n=31) than in diffuse vasospasm (n=33)
      (40.9+/-9.4 vs. 23.3+/-9.2%, p<0.0001). The Cs-Ao difference of malondialdehyde
      modified low-density lipoprotein (MDA-LDL) level, as a marker of
      atherothrombosis, in focal vasospasm increased significantly as compared with
      diffuse vasospasm (6.9+/-6.7 vs. 1.2+/-5.7 U/L, p=0.001). In a multiple-logistic
      regression analysis with the traditional risk factors, the Cs-Ao difference of
      MDA-LDL level was a variable differing independently between the 2 types of
      vasospasm. CONCLUSIONS: Higher MDA-LDL levels were observed in the coronary
      circulation in patients with focal vasospasm than in those with diffuse
      vasospasm. Under these conditions, the dramatically increased percent plaque
      volume in cases with focal vasoconstriction may play an important role in the
      development of acute coronary events.

PMID- 18614251
TI  - Early detection of coronary artery disease by 64-slice multidetector computed
      tomography in asymptomatic hypertensive high-risk patients.
AB  - BACKGROUND: The 64-slice multidetector-row computed tomography (MDCT) is an
      accurate noninvasive technique for assessing the degree of luminal narrowing in
      coronary arteries of patients with chronic ischemic disease. Aim of this study
      was to determine the value of MDCT in comparison to invasive coronary angiography
      (ICA) for detecting the presence and extent of coronary atherosclerotic plaques
      in a population of asymptomatic, hypertensive patients considered to be at high
      risk for cardiovascular events. METHODS: We studied 67 asymptomatic, hypertensive
      patients at high-risk (Euro Score >5%). All patients had negative or
      nondiagnostic findings at exercise stress testing and therefore underwent both
      MDCT and ICA. RESULTS: In the per-patient analysis, MDCT correctly identified
      16/17 (94%) patients with significant coronary artery disease involving at least
      1 vessel and 48/50 (96%) normal subjects. In the per-segment analysis, MDCT
      correctly detected 21/22 (95%) coronary segments with a stenosis >or=50% and
      856/868 (98%) normal segments, with a high negative predictivity of normal scans
      (100%). There was a good concordance between MDCT and ICA, with a high Pearson
      correlation coefficient between the coronary narrowings with the two techniques
      (r=0.84, p<0.01). Mean coronary calcium score was higher for the 17 patients with
      significant coronary artery disease on ICA than in the 50 patients without (422+/
      223 HU vs 72+/-21 HU p<0.001). The ROC curves identified 160 as the best calcium
      volumetric score cut-off value able to identify >or=1 significant coronary
      stenosis with sensitivity 88% and specificity 85%. CONCLUSIONS: MDCT is an
      excellent noninvasive technique for early identification of significant coronary
      stenoses in high risk asymptomatic hypertensive patients and might provide unique
      information for the screening of this broad population.

PMID- 18614252
TI  - Prevalence of VTEC O157 in dairy and veal herds and risk factors for veal herds.
AB  - The aim of this study was to determine the herd prevalence of veal and dairy
      herds and to identify risk factors for VTEC O157 positive veal herds. The study
      was based on monitoring data from November 1996 through July 2005 of 1051 dairy
      herds and 930 veal herds. The herd level prevalence (95% CI) was 8.0% (6.4-9.6)
      for dairy herds and 12.6% (10.5-14.7) for veal herds. Within the population of
      veal herds, a prevalence of 39.8% (33.9-45.6) was found for pink veal herds (n =
      269) and 1.5% (0.7-2.8) for white veal herds (n = 661). Multivariable logistic
      regression showed that the type of veal (pink vs. white; OR = 21.6; 95% CI: 10.4
      45.0), ventilation (mechanical vs. natural; OR = 0.4; 95% CI: 0.2-0.8), time
      between arrival in the herd and sampling (3-5 months vs. 0-2 months: OR = 2.33;
      95% CI: 1.1-5.1, > or = 6 months vs. 0-2 months: OR = 4.11; CI: 1.9-8.9), other
      feed than the 7 most common (yes vs. no; OR = 2.1; 95% CI: 1.2-3.7) and at least
      one dog present in the stable (yes vs. no; OR = 2.6; 95% CI: 1.5-4.6) were
      significantly (P < 0.05) associated with the presence of VTEC O157. The large
      difference in the VTEC O157 prevalences for pink veal and white veal production
      might have been caused by a very different management of these type of herds.
      However, this could not be studied with the data collected.

PMID- 18614253
TI  - Genetic variation of Listeria monocytogenes isolates from domestic and imported
      foods in Japan.
AB  - Phylogenetic analyses were carried out on a total of 118 Listeria monocytogenes
      isolates from foods or food processing environments, and 7 isolates from
      listeriosis patients in Japan to evaluate the genetic variation in the pathogen
      in this country. Isolates of serotypes 1/2a, 1/2b and 4b were mainly examined to
      assess the risk of exposure of humans to L. monocytogenes from foods in Japan.
      The nucleotide sequences of the part of the iap gene that contains the region
      encoding the threonine-asparagine repeat units were determined in order to
      construct phylogenetic trees of the isolates investigated. A phylogram showed
      high genetic diversity among lineage 2 isolates, while the lineage 1 isolates
      showed clonal characteristics. The results of the genetic analyses suggested the
      presence of rare putative lineage 3 isolates and epidemic clone I (ECI) isolates
      in foods in Japan. The results showed that ECI was also isolated from listeriosis
      patients. The genetic variation in L. monocytogenes in Japan reported here
      suggests the necessity of monitoring the pathogen in foods and environments in
      addition to surveillance of listeriosis patients.

PMID- 18614254
TI  - Subcellular compartment targeting of layered double hydroxide nanoparticles.
AB  - Current investigations show that layered double hydroxide (LDH) nanoparticles
      have high potential as effective non-viral agents for cellular drug delivery due
      to their low cytotoxicity, good biocompatibility, high drug loading, control of
      particle size and shape, targeted delivery and drug release control. Two types of
      Mg(2)Al-LDH nanoparticles with fluorescein isothiocyanate (FITC) were
      controllably prepared. One is morphologically featured as typical hexagonal
      sheets (50-150 nm laterally wide and 10-20 nm thick), while the other as typical
      rods (30-60 nm wide and 100-200 nm long). These LDH(FTIC) nanoparticles are
      observed to immediately transfect into different mammalian cell lines. We found
      that internalized LDH(FITC) nanorods are quickly translocated into the nucleus
      while internalized LDH(FITC) nanosheets are retained in the cytoplasm. Inhibition
      experiments show that the cellular uptake is a clathrin-mediated time- and
      concentration-dependent endocytosis. Endosomal escape of LDH(FITC) nanoparticles
      is suggested to occur through the deacidification of LDH nanoparticles. Since
      quick nuclear targeting of LDH(FITC) nanorods requires an active process, and
      although the exact mechanism is yet to be fully understood, it probably involves
      an active transport via microtubule-mediated trafficking processes. Targeted
      addressing of two major subcellular compartments by simply controlling the
      particle morphology/size could find a number of applications in cellular
      biomedicine.

PMID- 18614255
TI  - Stat3 downstream genes serve as biomarkers in human lung carcinomas and chronic
      obstructive pulmonary disease.
AB  - Smoking causes lung cancer and chronic obstructive pulmonary disease (COPD) that
      impose severe health problem to humans. Both diseases are related to each other
      and can be induced by chronic inflammation in the lung. To identify the molecular
      mechanism for lung cancer formation, a CCSP-rtTA/(teto)(7)Stat3C bitransgenic
      model was generated recently. In this model, persistent activation of the Stat3
      signaling pathway induced pulmonary inflammation and adenocarcinoma formation in
      the lung. A group of Stat3 downstream genes were identified by Affymetrix
      GeneChip microarray analysis that can be used as biomarkers for lung cancer
      diagnosis and prognosis. To determine which human lung cancers are related to the
      Stat3 pathway, multiple Stat3 downstream genes were screened in human lung
      cancers (adenocarcinomas and squamous cell carcinomas) and lung tissue with COPD.
      In both cancer and COPD, the Stat3 gene was up-regulated. A panel of Stat3-up
      regulated downstream genes in mice was up-regulated in human adenocarcinomas, but
      not in human squamous cell carcinomas. This panel of genes was also modestly up
      regulated in lung tissue with COPD from patients with a history of smoking and
      not up-regulated in those without histories of smoking. Several Stat3-down
      regulated downstream genes also showed differential expression patterns in
      carcinoma and COPD. These studies support a concept that Stat3 is a potent
      oncogenic molecule that plays a role in formation of lung adenocarcinomas in both
      mice and humans. The carcinogenesis of adenocarcinoma and squamous cell carcinoma
      is mediated by different molecular mechanisms and pathways in vivo. Stat3 and its
      downstream genes can serve as biomarkers for lung adenocarcinoma and COPD
      diagnosis and prognosis in mice and humans.

PMID- 18614258
TI  - Antimicrobial studies of some novel quinazolinones fused with [1,2,4]-triazole,
      [1,2,4]-triazine and [1,2,4,5]-tetrazine rings.
AB  - Three series of novel and new fused heterocyclic systems, viz. triazolo[4,3-a]
      quinazolin-7-ones (4), [1,2,4,5]-tetrazino[4,3-a]-quinazolin-8-ones (6) and
      indolo[2,3-c][1,2,4]-triazino[4,3-a]-quinazolin-8-ones (8) have been synthesized
      from the key intermediate 3-(substituted-phenyl)-2-hydrazino-quinazolin-4-ones
      (3). Thus, condensation of (3) with appropriate aromatic acids in the presence of
      DCC in dichloromethane afforded the fused system (4), while reaction of (3) with
      isatin in methanol gave the corresponding Schiff base (7) which on
      cyclodehydration furnished another fused heterocyclic system (8). The
      intermediate (3) on refluxing with substituted-phenylisothiocyanate gave the
      substituted-thiosemicarbazide (5), which on oxidative cyclization with bromine in
      CCl(4) furnished the novel fused system (6). The structures of intermediate and
      final compounds have been determined by means of IR, (1)H NMR, (13)C NMR, UV and
      elemental analysis. All the synthesized compounds have been screened for their
      antibacterial activity against gram-negative bacteria, Escherichia coli,
      Pseudomonas aeruginosa and gram-positive bacteria, Streptococcus pneumoniae,
      Bacillus subtilis, as well as demonstrated significant antifungal activity
      against fungi viz. Candida albicans, Aspergillus fumigatus, Aspergillus flavus,
      and Aspergillus niger.

PMID- 18614257
TI  - Effects of age on clock gene expression in the rhesus macaque pituitary gland.
AB  - Recent studies have shown that circadian clock genes are expressed in various
      peripheral tissues, raising the possibility that multiple clocks regulate
      circadian physiology. To study clock gene expression in the rhesus macaque
      pituitary gland we used gene microarray data and found that the pituitary glands
      of young and old adult males express several components of the circadian clock
      (Per1, Per2, Cry1, Bmal1, Clock, Rev-erbalpha and Csnk1varepsilon). Semi
      quantitative reverse-transcription polymerase chain reaction (sqRT-PCR) confirmed
      the presence of these core-clock genes and detected significant age-related
      differences in the expression of Per2. sqRT-PCR also showed differential
      expression of core-clock genes at two opposing time-points over the 24-h day,
      with greater expression of Per2 and Bmal1 (P<0.05) at 1300h as compared to 0100h.
      Immunohistochemistry revealed rhythmic expression of REV-ERBalpha in the
      pituitary glands of female macaques. These data provide evidence that the rhesus
      macaque pituitary gland expresses core-clock genes and their associated protein
      products in a 24-h rhythmic pattern, and that their expression is moderately
      impacted by aging processes.

PMID- 18614256
TI  - Menopause and the human hypothalamus: evidence for the role of
      kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback.
AB  - Menopause is characterized by depletion of ovarian follicles, a reduction of
      ovarian hormones to castrate levels and elevated levels of serum gonadotropins.
      Rather than degenerating, the reproductive neuroendocrine axis in postmenopausal
      women is intact and responds robustly to the removal of ovarian hormones. Studies
      in both human and non-human primates provide evidence that the gonadotropin
      hypersecretion in postmenopausal women is secondary to increased gonadotropin
      releasing hormone (GnRH) secretion from the hypothalamus. In addition, menopause
      is accompanied by hypertrophy of neurons in the infundibular (arcuate) nucleus
      expressing KiSS-1, neurokinin B (NKB), substance P, dynorphin and estrogen
      receptor alpha (ERalpha) mRNA. Ovariectomy in experimental animals induces nearly
      identical findings, providing evidence that these changes are a compensatory
      response to ovarian failure. The anatomical site of the hypertrophied neurons, as
      well as the extensive data implicating kisspeptin, NKB and dynorphin in the
      regulation of GnRH secretion, provide compelling evidence that these neurons are
      part of the neural network responsible for the increased levels of serum
      gonadotropins in postmenopausal women. We propose that neurons expressing KiSS-1,
      NKB, substance P, dynorphin and ERalpha mRNA in the infundibular nucleus play an
      important role in sex-steroid feedback on gonadotropin secretion in the human.

PMID- 18614259
TI  - Anti-HIV evaluation of benzo[d]isothiazole hydrazones.
AB  - The synthesis and the anti-HIV-1 activity of novel benzo[d]isothiazole hydrazones
      are reported. Target compounds tested in MT-4 cells cultures for their anti-HIV
      properties against wild type HIV-1 and HIV strains carrying clinically relevant
      mutations (EFV(R), Y181C and K103/Y181C) showed good activity against wild type
      HIV-1 and against the EFV(R) mutant. In terms of SAR the relevant result was
      that, in the class of benzisothiazole hydrazones, the benzo[d]isothiazol-3(2H)
      one moiety (compounds 1 and 4) is an essential structural requirement for the
      antiretroviral activity.

PMID- 18614260
TI  - [Diagnosis training].

PMID- 18614261
TI  - Deleterious effects of high-fat diet on perinatal and postweaning periods in
      adult rat offspring.
AB  - BACKGROUND & AIMS: Pre- and postnatal environmental changes can reset the
      developmental path during intrauterine development leading to obesity and
      cardiovascular and metabolic disorders later in life. The effects of high-fat
      diets on body mass, fat mass, the plasma level of glucose, insulin and leptin, as
      well as the insulin/glucose ratio and cardiovascular parameters in adult rat
      offspring were studied. METHODS: Pregnant Wistar rats in a standard chow group
      (SC) or high-fat chow group (HFC), at weaning their SC and HFC offspring were
      randomly divided into two postnatal groups: fed on SC or HFC. With euthanasia at
      6-month-old, three-way ANOVA there were three-factor interactions among gender,
      perinatal diet and postweaning diet to body mass (BM), BP, left ventricle (LV)
      thickness, carbohydrate metabolism, plasma corticosterone concentrations and
      leptin/fat mass/adipocyte size pattern. RESULTS: HFC/SC and SC/HFC offspring of
      both genders had high BM and BP, which were increased in HFC/HFC offspring. There
      was hyperinsulinism, hyperleptinemia, as well as high insulin/glucose ratio and
      high plasma corticosterone concentrations mainly in HFC/HFC offspring with
      adipocytes and LV hypertrophy. CONCLUSIONS: Postweaning HFC was deleterious to
      the health of adult offspring from dams fed HFC during pregnancy and then during
      the first half of lactation period. HFC administrated in both periods shows
      supplementary effects, elevating BP with consequent LV hypertrophy, altering
      carbohydrate metabolism, plasma corticosterone concentrations and disturbing
      leptin/fat mass/adipocyte size pattern.

PMID- 18614262
TI  - Comparison of self-reported and recorded vaccinations and health effects in
      Australian Gulf War veterans.
AB  - BACKGROUND: Vaccinations, and multiple vaccinations in particular, have been
      associated with adverse health effects in veterans of the 1990/1991 Gulf War.
      However, exposure assessment has usually been based on self-report and recall
      bias may have influenced the results. METHODS: We investigated agreement between
      self-reported and recorded vaccinations and the relationship with health status
      in Australian Gulf War veterans. RESULTS: Agreement between self-reported and
      recorded vaccinations was highest for plague (kappa=0.80), and kappa coefficients
      were greater than 0.60 for polio and 'other unlisted' vaccines, between 0.41 and
      0.60 for hepatitis B, hepatitis A, typhoid and pertussis, and less than 0.40 for
      the other listed vaccines. The associations of increasing number of self-reported
      vaccinations in dose response relationships with total number of symptoms,
      functional impairment, and poorer physical health were not observed when based on
      recorded vaccination data, although the actual difference in estimates was small
      and statistically significant only for total number of symptoms. CONCLUSIONS:
      Vaccinations were not associated with adverse health effects when exposure
      assessment was based on recorded vaccinations. It would be prudent that future
      research studies should be based on recorded vaccination data.

PMID- 18614263
TI  - The vicarious learning pathway to fear 40 years on.
AB  - Forty years on from the initial idea that fears could be learnt vicariously
      through observing other people's responses to a situation or stimulus, this
      review looks at the evidence for this theory as an explanatory model of clinical
      fear. First, we review early experimental evidence that fears can be learnt
      vicariously before turning to the evidence from both primate and human research
      that clinical fears can be acquired in this way. Finally, we review recent
      evidence from research on non-anxious children. Throughout the review we
      highlight problems and areas for future research. We conclude by exploring the
      likely underlying mechanisms in the vicarious learning of fear and the resulting
      clinical implications.

PMID- 18614264
TI  - Forty days and forty nights: a biocultural perspective on postpartum practices in
      the Amazon.
AB  - The immediate postpartum period is recognized as a special time in many societies
      and is commonly associated with food and work restrictions. The logic of food
      restrictions during a period of increased energy and protein needs has been
      challenged, but few data are available to test the impact of these practices on
      the diets of lactating women. In the eastern Amazon the immediate postpartum
      period is referred to as resguardo, lasts for 40-41 days and includes food taboos
      and work restrictions. Taking a biocultural perspective, this paper combines data
      on the beliefs and attitudes surrounding the practice of resguardo with
      quantitative data on the actual dietary intakes and activity patterns of a cohort
      of 23 lactating women followed from birth through 15 months postpartum. This
      paper addresses three topics: (1) shared ideals regarding resguardo; (2)
      adherence to food and work restrictions; and (3) the impact of these practices on
      women's dietary intakes and energy expenditure. The results show that the
      majority of women adhered to food taboos and work restrictions. During resguardo
      energy expenditure in physical activity was lower, reducing women's energy needs
      and allowing them to devote more time to infant care. However, energy intakes
      were also lower. The reduction in dietary intake was impacted more by work
      restrictions and the loss of women in subsistence tasks during resguardo than by
      adherence to food taboos. In addition to altering maternal energetic strategies,
      resguardo served an important social function by reinforcing bonds and, for young
      women, marking the transition to womanhood.

PMID- 18614265
TI  - Incidental retrieval of emotional contexts in post-traumatic stress disorder and
      depression: an fMRI study.
AB  - In the present study, we used fMRI to assess patients suffering from post
      traumatic stress disorder (PTSD) or depression, and trauma-exposed controls,
      during an episodic memory retrieval task that included non-trauma-related
      emotional information. In the study phase of the task neutral pictures were
      presented in emotional or neutral contexts. Participants were scanned during the
      test phase, when they were presented with old and new neutral images in a yes/no
      recognition memory task. fMRI results for the contrast between old and new items
      revealed activation in a predominantly left-sided network of cortical regions
      including the left middle temporal, bilateral posterior cingulate, and left
      prefrontal cortices. Activity common to all three groups when correctly judging
      pictures encoded in emotional contexts was much more limited. Relative to the
      control and depressed groups the PTSD group exhibited greater sensitivity to
      correctly recognised stimuli in the left amygdala/ventral striatum and right
      occipital cortex, and more specific sensitivity to items encoded in emotional
      contexts in the right precuneus, left superior frontal gyrus, and bilateral
      insula. These results are consistent with a substantially intact neural system
      supporting episodic retrieval in patients suffering from PTSD. Moreover, there
      was little indication that PTSD is associated with a marked change in the way
      negatively valenced information, not of personal significance, is processed.

PMID- 18614266
TI  - Current regulatory toxicology perspectives on the development of herbal medicines
      to prescription drug products in the United States.
AB  - Toxicological studies constitute an essential part of the effort in developing an
      herbal medicine into a drug product. The US food and drug administration (FDA)
      published a guidance to assist academic and industry sponsors in the development
      of this unique group of drug products, and has recently approved an new drug
      application (NDA) based on green tea extract (Veregen) for topical treatment of
      genital and perianal warts. In this article, current regulatory views on issues
      related to requirements and recommendations on various types of nonclinical
      toxicity studies in support of clinical trials and filing an NDA for a herbal
      medicine, including pharm/tox aspects of green tea extract (Veregen) NDA, are
      discussed. Topics include nonclinical pharmacology/toxicology perspectives on
      herbal nomenclature and its identification, previous human experience and initial
      clinical trial proposal, regulatory aspects of acute toxicity studies, chronic
      toxicity studies, mutagenicity studies, reproductive toxicity studies, and
      carcinogenicity studies on botanicals. Certain regulatory review-related issues
      are also presented. It is anticipated that through a proactive two-way
      communication between the Agency and the sponsor, toxicological development of
      botanical drug product can be significantly facilitated.

PMID- 18614268
TI  - A human dietary risk assessment associated with glycoalkaloid responses of potato
      to Colorado potato beetle defoliation.
AB  - A quantitative human dietary risk assessment was conducted using the
      glycoalkaloid concentrations measured from tubers of plants defoliated by
      Colorado potato beetles and undefoliated (control). There was a significantly
      greater production of glycoalkaloids for defoliated plants compared to control
      plants for both skin and inner tissue of tubers. The dietary risk posed to
      different human subgroups associated with the consumption of potatoes was
      estimated for the 50th, 95th, and 99.9th percentile US national consumption
      values. Exposures were compared to a toxic threshold of 1.0mg/kg body weight.
      Defoliation by Colorado potato beetles increased dietary risk by approximately
      48%. Glycoalkaloid concentrations within the inner tissue of tubers, including
      undefoliated controls, exceeded the toxic threshold for all human subgroups at
      less than the 99.9th percentile of exposure, but not the 95th percentile.

PMID- 18614267
TI  - Tissue distribution and proinflammatory cytokine gene expression following acute
      oral exposure to deoxynivalenol: comparison of weanling and adult mice.
AB  - The frequent presence of deoxynivalenol (DON) in cereal-based foods and the high
      intake of these foods by children raises particular concerns about the relative
      susceptibility of this subpopulation to adverse effects evoked by this mycotoxin.
      We tested the hypothesis that both toxicokinetics and proinflammatory cytokine
      gene expression following a oral DON exposure at 5mg/kg bw differ between
      weanling (3-4 wk) and young adult (8-10 wk) female mice. DON was rapidly taken up
      with maximum plasma concentrations reaching 1.0 microg/ml in adult mice at 15
      min, whereas DON levels were approximately twice as much in weanling mice at
      these times. DON was rapidly cleared in both weanling and adult mice with
      concentrations being reduced by 78% and 81% of the peak levels, respectively,
      after 2h. DON accumulation and clearance in spleen, liver, lung and kidney
      followed similar kinetics to that of plasma with tissue burdens also reaching
      twice that of adult mice. When TNF-alpha, IL-1beta and IL-6 mRNAs in spleens (a
      primary source of systemic proinflammatory cytokines) were used as biomarkers of
      the DON's effects, expression of these mRNAs was two to three times greater in
      weanling than adult mouse. However, differences in proinflammatory cytokine
      expression were less robust or not apparent in the liver or lung. Taken together,
      these data suggest that young mice are modestly more susceptible than adult mice
      to the adverse effects of DON and that this might result from a greater toxin
      tissue burden.

PMID- 18614269
TI  - Glycoalkaloid responses of potato to Colorado potato beetle defoliation.
AB  - Two experiments were conducted to measure the glycoalkaloid concentrations of
      potato tubers in response to Colorado potato beetle and manual defoliation. For
      plants defoliated by Colorado potato beetles, there was a significantly greater
      production of glycoalkaloids than in control plants and manually defoliated
      plants for both skin and inner tissue of tubers in experiment 1. In experiment 1,
      there was a 58.1% and 48.3% increase in glycoalkaloids in skin and inner tissue
      of tubers, respectively, from plants defoliated at high levels by Colorado potato
      beetles compared to control plants. In experiment 2, although a significant
      difference in glycoalkaloid concentration was not observed among the treatments,
      the skin and inner tissue of tubers from plants defoliated at high levels by
      Colorado potato beetles increased glycoalkaloid concentration by 23.4% and 14.5%,
      respectively, compared to tubers from control plants. In experiment 1, the
      concentration of tuber extract required to reduce Chinese hamster ovary (CHO)
      cellular proliferation by 50% was 10-fold less for the skin versus the inner
      tissue, indicating that skin tissue was more toxic under the in vitro conditions
      of this assay.

PMID- 18614270
TI  - Arsenic, cadmium and lead in medicinal herbs and their fractionation.
AB  - Arsenic, cadmium and lead were determined for quality control monitoring purposes
      of Bulgarian herbs and their infusions by inductively coupled plasma mass
      spectrometry and electrothermal atomic absorption spectrometry. Twelve samples of
      yarrow (Achillea millefolium), 18 of chamomile (Flores Chamomillae), 8 of
      bearberry leaves (Folia uvae ursi), 24 of peppermint (Mentha piperitae folium),
      10 of hibiscus (Hibiscus sabdariffa), 14 of oregano (Origanum vulgare) and 12 of
      thyme (Thymus serpyllum) were analyzed. The studied toxic elements were present
      in the medicinal plants (12-225 microg/kg As, 15-268 microg/kg Cd, 0.2-8.6 mg/kg
      Pb). Arsenic was found in all herbal infusions at levels up to 0.4 microg/l.
      Cadmium was present in infusions of chamomile, hibiscus, peppermint and thyme at
      levels up to 0.7 microg/l. Lead was detected only in hibiscus infusions (2-3
      microg/l). It was established that the major part of arsenic and lead in herbal
      infusions existed in biomacromolecular fraction. Cadmium appears to be present
      mainly in cationic form at pH 1 (stomach acidity), but at pH 7.6 (intestine
      acidity) there is a non-cationic fraction as well.

PMID- 18614271
TI  - An animal model to study health effects during continuous low-dose exposure to
      the nerve agent VX.
AB  - In the present study, we have developed an animal model to study long-term health
      effects of continuous exposure of toxic chemical agents, in awake, freely moving
      rats. The aim was to evaluate the effect of low-dose exposure of the nerve agent
      VX, and to find specific biomarkers for intoxication. To exclude the influence of
      stress, we used an implanted radio-telemetric device for online registration of
      physiological parameters, and an osmotic pump, implanted subcutaneously, for
      continuous exposure of the toxic agent. Our results showed that the lowest
      observable effect dose of VX in Wistar rats was 5 microg/kg/24 h, after
      continuous exposure by the osmotic pump. Although we observed significant
      inhibition of acetylcholinesterase (AChE) in blood and a significant decrease in
      body weight gain at this dose, no change in blood pressure, heart rate or
      respiratory rate was registered. However, a significant decrease in the thyroid
      hormone, free T4, was measured in blood after 8 weeks, indicating that low doses
      of VX might affect the thyroid function. Rats given repeated daily injections
      were more sensitive to VX and needed only 1/10 of the concentration to reach a
      similar level of AChE inhibition, compared to animals exposed by the osmotic
      pump. Moreover, the results showed that exposure of VX in our experimental
      design, does not induce an increase in corticosterone blood levels. Thus, the
      model used in this investigation renders minimal stress and will not cause
      unnecessary pain to the animals, indicating that this model could be a useful
      tool to study long-term effects of various toxic substances in freely moving
      rats.

PMID- 18614272
TI  - Predictive value of PET-CT imaging versus AGO-scoring in patients planned for
      cytoreductive surgery in recurrent ovarian cancer.
AB  - OBJECTIVE: To assess the predictive value of positron emission tomography
      computed tomography (PET-CT) imaging in comparison to AGO-scoring in patients
      planned for cytoreductive surgery in recurrent ovarian cancer. MATERIALS AND
      METHODS: 33 patients who had received a PET-CT for suspicion of recurrent ovarian
      cancer between 12/2003 and 08/2007 were included in the retrospective analysis.
      Indication for PET-CT was based on blood tumor markers Ca 125 or Ca 72-4 and
      clinical symptoms. Scanning was performed on a Philips Gemini System covering the
      body from the neck to the thighs one hour after administration of 200MBq
      fluorodesoxyglucose. PET-CT, surgery and the patient records were reviewed to
      analyze the predictive value of PET-CT in comparison to an AGO-scoring system
      based on clinical parameters with regard to the prediction of full resectability
      of abdominal tumor spread. RESULTS: The statistical analysis of this data showed
      a sensitivity of 73% (95% C.I., 39-94%) and specificity of 80% (95% C.I., 29-97%)
      for AGO-scoring with a positive predictive value of 89% and a negative predictive
      value of 57%. PET-CT achieved a sensitivity of 100% (95% C.I., 72-100%) and
      specificity of 60% (95% C.I. 15-94%), with a positive predictive value of 85% and
      negative predictive value of 100%. Further analysis of the data of operated
      patients with concordant PET-CT and AGO-score (12/16) showed a very good
      prediction of full resectability with a sensitivity of 100% (95% C.I., 63-100%),
      specificity of 75% (95% C.I., 20-96%), positive predictive value of 89% and
      negative predictive value of 100%. CONCLUSION: PET-CT and the AGO-score offer
      good tools to determine patients for full resectability in recurrent ovarian
      cancer. PET-CT has a higher negative and the AGO score a higher positive
      predictive value, and the combination of both improves the diagnostic accuracy.

PMID- 18614273
TI  - The effectiveness of market-based conservation in the tropics: forest
      certification in Ecuador and Bolivia.
AB  - During the last decade, forest certification has gained momentum as a market
      based conservation strategy in tropical forest countries. Certification has been
      promoted to enhance forest management in countries where governance capacities
      are insufficient to adequately manage natural resources and enforce pertinent
      regulations, given that certification relies largely on non-governmental
      organisations and private businesses. However, at present there are few tropical
      countries with large areas of certified forests. In this study, we conducted semi
      structured stakeholder interviews in Ecuador and Bolivia to identify key
      framework conditions that influence the costs and benefits for companies to
      switch from conventional to certified forestry operations. Bolivia has a much
      greater relative area under certified forest management than Ecuador and also
      significantly more certified producers. The difference in the success of
      certification between both countries is particularly notable because Bolivia is a
      poorer country with more widespread corruption, and is landlocked with less
      access to export routes. Despite these factors, several characteristics of the
      Bolivian forest industry contribute to lower additional costs of certified forest
      management compared to Ecuador. Bolivia has stronger government enforcement of
      forestry regulations a fact that increases the cost of illegal logging,
      management units are larger, and vertical integration in the process chain from
      timber extraction to markets is higher. Moreover, forestry laws in Bolivia are
      highly compatible with certification requirements, and the government provides
      significant tax benefits to certified producers. Results from this study suggest
      that certification can be successful in countries where governments have limited
      governance capacity. However, the economic incentives for certification do not
      only arise from favourable market conditions. Certification is likely to be more
      successful where governments enforce forestry laws, provide financial incentives
      for certified forestry, and provide land tenure security, and where large-scale
      and vertically integrated forestry operations are commercially feasible. For this
      reason, at present, there are few developing countries where forest certification
      is likely to achieve widespread success.

PMID- 18614274
TI  - PSA doubling time versus PSA velocity to predict high-risk prostate cancer: data
      from the Baltimore Longitudinal Study of Aging.
AB  - BACKGROUND: Our group has previously shown that prostate-specific antigen (PSA)
      velocity (PSAV) is associated with the presence of life-threatening prostate
      cancer. Less is known about the relative utility of pretreatment PSA doubling
      time (PSA DT) to predict tumor aggressiveness. OBJECTIVE: To compare the utility
      of PSAV and PSA DT for the prediction of life-threatening prostate cancer.
      DESIGN, SETTING, AND PARTICIPANTS: From the Baltimore Longitudinal Study of
      Aging, we identified 681 men with serial PSA measurements. MEASUREMENTS: Receiver
      operating characteristic analysis was used to evaluate the relationship between
      PSAV, PSA DT, and the presence of high-risk disease. RESULTS AND LIMITATIONS:
      Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among
      men with high-risk or fatal prostate cancer than men without it. By contrast, PSA
      DT was not significantly associated with high-risk or fatal disease. On
      multivariate analysis, including age, date of diagnosis, and PSA, the addition of
      PSAV significantly improved the concordance index from 0.85 to 0.88 (p<0.001),
      whereas PSA DT did not. CONCLUSIONS: These data suggest that PSAV is more useful
      than PSA DT in the pretreatment setting to help identify those men with life
      threatening disease.

PMID- 18614275
TI  - Pregnant woman presenting with a gross retroperitoneal mass: surgical treatment
      with caval replacement.
AB  - A 40-year-old woman in the twenty-fifth week of pregnancy presented with a gross
      retroperitoneal mass. At the end of the pregnancy, the patient was submitted to
      surgery, and the gross infiltration of the inferior vena cava wall required the
      resection of the vena cava with its prosthetic substitution. The
      histopathological examination demonstrated the presence of a leiomyosarcoma of
      the inferior vena cava. An electronic video supplement showing the most important
      intraoperative passages is available online at doi:10.1016/j.eururo.2008.06.074.

PMID- 18614276
TI  - Regulation of breast cancer-associated aromatase promoters.
AB  - By converting androstenedione to estrone, or testosterone to estradiol, aromatase
      is a key enzyme in estrogen biosynthesis. Encoded by a single gene CYP19,
      aromatase is expressed in various tissues, including ovary, placenta, bone,
      brain, skin, and adipose tissue, via partially tissue-specific promoters, and is
      essential for normal estrogen-dependent physiological functions. In disease-free
      breast tissue, aromatase mRNA is primarily transcribed from the weak promoter I.4
      and maintained at low levels in breast adipose stromal fibroblasts. In breast
      cancer a distinct set of aromatase promoters, i.e. I.3, II, and I.7, is
      activated, leading to a marked increase in aromatase expression in breast tumors
      and breast adipose tissue adjacent to a breast tumor, and a consequent local
      overproduction of estrogen that promotes growth and progression of breast cancer.
      In addition, the total amount of promoter I.4-specific aromatase transcript in
      breast adipose fibroblasts may also be increased due to both cytokine-induced
      desmoplastic reaction and cytokine-stimulated promoter I.4 activity in breast
      cancer. Targeting aromatase has proven beneficial in treating breast cancer,
      since aromatase inhibitors are the most effective endocrine treatment of breast
      cancer to date. However, aromatase inhibitors cause major side effects such as
      bone loss and abnormal lipid metabolism, due to indiscriminate reduction of
      aromatase activity in all expression sites of the body. Therefore, inhibition of
      aromatase expression via breast cancer-associated aromatase promoters is a useful
      strategy to selectively block local aromatase production, and hence estrogen
      synthesis, in breast cancer. This review will summarize the significant findings
      on regulation of the breast cancer-associated aromatase promoters, and highlight
      the discovery of chemical compounds and nuclear receptor ligands that
      specifically inhibit activation of these aromatase promoters. Clinical side
      effects of these agents require development of new drugs with better specificity
      and efficacy, and epigenetic therapies with breast cancer tissue-selective
      aromatase siRNA-conjugated nanoparticles.

PMID- 18614277
TI  - Heterogeneous photo-Fenton degradation of polyacrylamide in aqueous solution over
      Fe(III)-SiO(2) catalyst.
AB  - This article presents preparation, characterization and evaluation of
      heterogeneous Fe(III)-SiO(2) catalysts for the photo-Fenton degradation of
      polyacrylamide (PAM) in aqueous solution. Fe(III)-SiO(2) catalysts are prepared
      by impregnation method with two iron salts as precursors, namely Fe(NO(3))(3) and
      FeSO(4), and are characterized by Brunauer-Emmett-Teller (BET), X-ray diffraction
      (XRD) and X-ray photoelectron spectroscopy (XPS) methods. The irradiated Fe(III)
      SiO(2) is complexed with 1,10-phenanthroline, then is measured by UV-vis-diffuse
      reflectance spectroscopy (UV-vis-DRS) and XPS to confirm the oxidation state of
      Fe in solid state. By investigating the photo-Fenton degradation of PAM in
      aqueous solution, the results indicate that Fe(III)-SiO(2) catalysts exhibit an
      excellent photocatalytic activity in the degradation of PAM. Moreover, the
      precursor species and the OH(-)/Fe mole ratio affect the photocatalytic activity
      of Fe(III)-SiO(2) catalysts to a certain extent. Finally, the amount of Fe ions
      leaching from the Fe(III)-SiO(2) catalysts is much low.

PMID- 18614278
TI  - Evaluation of the distribution patterns of Pb, Cu and Cd from MSWI fly ash during
      thermal treatment by sequential extraction procedure.
AB  - Municipal solid waste incinerator (MSWI) fly ash was frequently classified as
      hazardous materials as the metals' concentration of toxicity characteristic
      leaching procedure (TCLP) exceeded regulations. Many studies have focused on
      reducing the concentration of TCLP using thermal treatment and increasing the
      application of thermally treated slag. However, the metal patterns in MSWI fly
      ash with or without thermal treatment have seldom been addressed. The main
      objective of this study was evaluation of the distribution patterns of Pb, Cu and
      Cd from MSWI fly ash during thermal treatment by sequential extraction procedure.
      The experimental parameters included the form of pretreatment, the proportion of
      bottom ash (bottom ash/fly ash, B/F=0, 0.1 and 1) and the retention time. The
      results indicated that (1) In comparison to raw fly ash, the distribution
      patterns of Pb, Cu and Cd become stable in thermally treated slag. (2) Washing
      pretreatment caused the Pb pattern to become stable, while the influence on Cu
      and Cd were not significant. (3) The distribution patterns of Pb, Cu, and Cd
      became more stable as the retention time increased. (4) Adding bottom ash could
      make the distribution patterns of Pb and Cd more stable.

PMID- 18614279
TI  - Photochemical removal of NO(2) by using 172-nm Xe(2) excimer lamp in N(2) or air
      at atmospheric pressure.
AB  - Photochemical removal of NO(2) in N(2) or air (5-20% O(2)) mixtures was studied
      by using 172-nm Xe(2) excimer lamps to develop a new simple photochemical
      aftertreatment technique of NO(2) in air at atmospheric pressure without using
      any catalysts. When a high power lamp (300 mW/cm(2)) was used, the conversion of
      NO(2) (200-1000 ppm) to N(2) and O(2) in N(2) was >93% after 1 min irradiation,
      whereas that to N(2)O(5), HNO(3), N(2), and O(2) in air (10% O(2)) was 100% after
      5s irradiation in a batch system. In a flow system, about 92% of NO(2) (200 ppm)
      in N(2) was converted to N(2) and O(2), whereas NO(2) (200-400 ppm) in air (20%
      O(2)) could be completely converted to N(2)O(5), HNO(3), N(2), and O(2) at a flow
      rate of 1l/min. It was found that NO could also be decomposed to N(2) and O(2)
      under 172-nm irradiation, though the removal rate is slower than that of NO(2) by
      a factor of 3.8. A simple model analysis assuming a consecutive reaction NO(2)-
      >NO-->N+O indicated that 86% of NO(2) is decomposed directly into N+O(2) and the
      rest is dissociated into NO+O under 172-nm irradiation. These results led us to
      conclude that the present technique is a new promising catalyst-free
      photochemical aftertreatment method of NO(2) in N(2) and air in a flow system.

PMID- 18614280
TI  - Degradation of nitrobenzene using titania photocatalyst co-doped with nitrogen
      and cerium under visible light illumination.
AB  - A type of nitrogen and cerium co-doped titania photocatalyst, which could degrade
      nitrobenzene under visible light irradiation, was prepared by the sol-gel route.
      Titanium isopropoxide, ammonium nitrate, and cerium nitrate were used as the
      sources of titanium, nitrogen, and cerium, respectively. X-ray diffraction (XRD),
      X-ray photoelectron spectroscopy (XPS), UV-vis diffusive reflectance spectroscopy
      (DRS), scanning electron microscopy (SEM), and N(2) adsorption-desorption
      isotherm were employed to characterize the as-prepared photocatalyst. The
      degradation of nitrobenzene under visible light illumination was taken as probe
      reaction to evaluate the photoactivity of the co-doped photocatalyst. The
      commercial TiO(2) photocatalyst (Degussa P25), which was thought as a high active
      photocatalyst, was chosen as standard photocatalyst to contrast the photoactivity
      of the nitrogen and cerium co-doped titania photocatalyst. The results showed
      that the photocatalytic performance of the nitrogen and cerium co-doped titania
      was related with the calcination temperature and the component. The nitrogen
      atoms were incorporated into the crystal of titania and could narrow the band gap
      energy. The doping cerium atoms existed in the forms of Ce(2)O(3) and dispersed
      on the surface of TiO(2). The improvement of the photocatalytic activity was
      ascribed to the synergistic effects of the nitrogen and cerium co-doping.

PMID- 18614281
TI  - Detoxification of simulated textile wastewater using a membraneless
      electrochemical reactor with immobilized peroxidase.
AB  - Simulated textile wastewater was degraded using a membraneless electrochemical
      reactor with immobilized peroxidase on the porous Celite. The optimal current
      density was 10 A m(-2), at which the highest amount of hydrogen (H(2)O(2)) could
      be generated. The decolorization efficiencies of the simulated wastewater using
      the electrochemical and electroenzymatic methods were 35% and 92%, respectively.
      Biodegradability, the ratio of 5-day biochemical oxygen demand to chemical oxygen
      demand (BOD(5)/COD), was enhanced about 1.88 times when using the
      electroenzymatic treatment rather than raw wastewater, which could not be
      achieved by the electrochemical treatment. The toxic unit (TU), calculated using
      the lethal concentration (LC(50)) of Daphnia magna (D. Magna), of effluent
      treated by electroenzymatic method was below 1, whereas those of simulated
      textile wastewater and effluent treated by electrochemical method were 11.4 and
      3.9, respectively.

PMID- 18614282
TI  - Effects of low-molecular-weight organic acids on Cu(II) adsorption onto
      hydroxyapatite nanoparticles.
AB  - Adsorption kinetics and adsorption isotherms of Cu(II) onto a nanosized
      hydroxyapatite (HAP) in the absence and presence of different low-molecular
      weight organic acids are studied in batch experiments. The results show that the
      adsorption kinetics of Cu(II) onto the HAP are best described by pseudo-second
      order model, and the adsorption isotherms of Cu(II) onto the HAP fit Dubinin
      Radushkevich model very well with high correlation coefficient (R(2)=0.97-0.99).
      The amount adsorbed of Cu(II) onto the HAP at pH 5.5 was much higher than that at
      pH 4.5. The presence of organic acids significantly decreased the adsorption
      quantity of Cu(II), clarifying the lower sorption affinities of Cu(II)-organic
      acid complexes onto the HAP rather than Cu(II) ion. The decreased maximal
      adsorption quantity of Cu(II) onto the HAP increased with the increasing
      logarithm of cumulative formation constants of Cu(II) and organic acids. The
      stronger coordination of organic acid with Cu(II), the more decreased Cu(II)
      adsorption quantity onto the HAP.

PMID- 18614283
TI  - Characteristics and mechanisms of phosphate adsorption onto basic oxygen furnace
      slag.
AB  - The adsorption characteristics of phosphate adsorption on the basic oxygen
      furnace (BOF) slag were identified as a function of pH and ion strengths in
      solution. In addition, adsorption mechanisms were investigated by conducting
      batch tests on both the hydrolysis and phosphate adsorption process of the BOF
      slag, and making a comparative analysis to gain newer insights into understanding
      the adsorption process. Results show that the adsorption capacity from 4.97 to
      3.71 mgP/g slag when the solution pH was increased from 2.0 to 13.0 and phosphate
      initial concentration was 50 mg/L, indicating that adsorption capacity is largely
      dependent upon the pH of the system. The results of the competitive adsorption
      between phosphate and typical anions found in wastewater, such as NO(3)(-),
      SO(4)(2-) and Cl(-), onto BOF slag reveal that BOF slag can selectively adsorb
      phosphate ions. The insignificant effect of NO(3)(-), SO(4)(2-) and Cl(-) on
      phosphate adsorption capacity indicates that phosphate adsorption is through a
      kind of inner-sphere complex reaction. During the adsorption process, the
      decrease of phosphate concentration in solution accompanied with an increase in
      pH values and concentrations of NO(3)(-), SO(4)(2-) and Cl(-) suggests that
      phosphate replaced the functional groups from the surface of BOF slag which
      infers that ligand exchange is the dominating mechanism for phosphate removal. At
      the same time, the simultaneous decreases in PO(4)(3-) and total calcium,
      magnesium and aluminum concentration in solution indicate that chemical reaction
      and precipitation are other mechanisms of phosphate removal.

PMID- 18614284
TI  - Durability of class C fly ash belite cement in simulated sodium chloride
      radioactive liquid waste: influence of temperature.
AB  - This work is a continuation of a previous durability study of class C fly ash
      belite cement (FABC-2-W) in simulated radioactive liquid waste (SRLW) that is
      very rich in sulphate salts. The same experimental methodology was applied in the
      present case, but with a SRLW rich in sodium chloride. The study was carried out
      by testing the flexural strength of mortars immersed in simulated radioactive
      liquid waste that was rich in chloride (0.5M), and demineralised water as a
      reference, at 20 and 40 degrees C over a period of 180 days. The reaction
      mechanism of chloride ions with the mortar was evaluated by scanning electron
      microscopy (SEM), porosity and pore-size distribution, and X-ray diffraction
      (XRD). The results showed that the FABC mortar was stable against simulated
      chloride radioactive liquid waste (SCRLW) attack at the two chosen temperatures.
      The enhancement of mechanical properties was a result of the formation of non
      expansive Friedel's salt inside the pores; accordingly, the microstructure was
      refined.

PMID- 18614285
TI  - Removal of hexachlorobenzene from soil by electrokinetically enhanced chemical
      oxidation.
AB  - This study investigates the feasibility of enhanced electrokinetic Fenton process
      for the remediation of hexachlorobenzene (HCB) in low permeable soil. Laboratory
      scale experiments were carried out in two different type of experimental setup to
      evaluate the influence of electrode positions in the system. Kaolin was
      artificially contaminated with HCB and treated by electrokinetic Fenton process.
      beta-Cyclodextrin was used to enhance the solubility of HCB in pore fluid.
      Results show that the position of electrodes in the system and the way in which
      Fenton's reagent was added to the system has a significant influence on the
      treatment efficiency.

PMID- 18614286
TI  - Utilization of bog iron ores as sorbents of heavy metals.
AB  - Sorption properties of bog iron ores with respect to Pb, Cu, Zn, Cr are evaluated
      at various pH. Maximum sorption determined in the experiments equals to 97.0,
      25.2, 25.5, 55.0mg/g for lead(II), copper(II), zinc(II), and chromium(III),
      respectively. Chromium(VI) is bound in the amount of up to 10.0mg/g. The values
      of desorption indicate that most of the metals remain stably bound to the surface
      of bog iron ores, indicating that the chemisorption process prevails. The metals
      are sorbed as cations at the pH values from 4 to 9. Within this pH range up to
      100% of the initial metal amount is immobilized. 90-100% of Cr(VI) is sorbed at
      pH between 3 and 5. Such properties, combined with favorable conditions of
      shallow mining and resultant low costs, may be regarded as an incentive for local
      utilization of bog iron ores in the environmental protection practice.

PMID- 18614287
TI  - No association between polymorphisms in the FACL4 (fatty acid-CoA ligase 4) gene
      and nonspecific mental retardation in Qin-Ba mountain region of China.
AB  - Mental retardation (MR) is a common form of cognitive impairment among children.
      The underlying causes of mental retardation are extremely heterogeneous and
      include significant genetic factors. Long chain fatty acid-CoA ligase 4 is the
      first gene shown to be involved in mental retardation and fatty-acid metabolism.
      FACL4 gene mutations in three Italian MR pedigrees have been reported as causing
      non-specific mental retardation. To investigate the possible genetic contribution
      of the FACL4 gene to non-specific mental retardation children of the Qin-Ba
      mountain region in China we performed an association study of 556 subjects (118
      NSMR, 116 borderline NSMR, and 322 controls) from the Han children of
      northwestern China using five common SNPs (rs5943427, rs12856122, rs5943418,
      rs7886473, and rs10126612) in the gene. No significant differences of genotypes
      and alleles frequencies from each single SNP between NSMR and controls were
      observed. Pairwise linkage disequilibrium analysis showed that four SNPs
      rs5943427, rs12856122, rs5943418, and rs7886473 were in strong linkage
      disequilibrium; therefore, a haplotype analysis was performed. However, there
      were no any significant differences in haplotype distributions between cases and
      controls. In conclusion, we have found no evidence for the FACL4 gene conferring
      susceptibility on non-specific mental retardation children of the Qin-Ba mountain
      region in China.

PMID- 18614288
TI  - The bite-raised condition in aged SAMP8 mice induces dendritic spine changes in
      the hippocampal region.
AB  - The present study examined the effect of the bite-raised condition on the number
      of dendritic spines on hippocampal pyramidal cells in SAMP8 mice and related the
      results with learning ability in a water maze test. Aged mice in the bite-raised
      condition had reduced learning ability and a lower number of CA1 pyramidal cell
      dendritic spines. The results suggest that the bite-raised condition exacerbates
      the age-related spatial learning impairment, and that this may be due to the
      degeneration of hippocampal dendritic spines.

PMID- 18614289
TI  - Fast non-genomic effects of progesterone-derived neurosteroids on nociceptive
      thresholds and pain symptoms.
AB  - Fast Inhibitory controls mediated by glycine (GlyRs) and GABAA receptors
      (GABAARs) play an important role to prevent the apparition of pathological pain
      symptoms of allodynia and hyperalgesia. The use of positive allosteric modulators
      of these receptors, specifically expressed in the spinal cord, may represent an
      interesting strategy to limit or block pain expression. In this study, we have
      used stereoisomers of progesterone metabolites, acting only via non-genomic
      effects, in order to evaluate the contribution of GlyRs and GABAARs for the
      reduction of mechanical and thermal heat hypernociception. We show that 3alpha
      neurosteroids were particularly efficient to elevate nociceptive thresholds in
      naive animal. It also reduced mechanical allodynia and thermal heat hyperalgesia
      in the carrageenan model of inflammatory pain. This effect is likely to be
      mediated by GABAA receptors since 3beta isomer was inefficient. More
      interestingly, 3alpha5beta neurosteroid was only efficient on mechanical
      allodynia while having no effect on thermal heat hyperalgesia. We characterized
      these paradoxical effects of 3alpha5beta neurosteroid using the strychnine and
      bicuculline models of allodynia. We clearly show that 3alpha5beta neurosteroid
      exerts an antinociceptive effect via a positive allosteric modulation of GABAARs
      but, at the same time, is pronociceptive by reducing GlyR function. This
      illustrates the importance of the inhibitory amino acid receptor channels and
      their allosteric modulators in spinal pain processing. Moreover, our results
      indicate that neurosteroids, which are synthesized in the dorsal horn of the
      spinal cord and have limited side effects, may be of significant interest in
      order to treat pathological pain symptoms.

PMID- 18614290
TI  - Central representation of cold-evoked pain relief in capsaicin induced pain: an
      event-related fMRI study.
AB  - The termination of an unpleasant or painful somatic condition can produce a
      rewarding sense of relief, even if the stimulus that causes the termination is
      itself unpleasant or painful under normal circumstances. We aimed to identify
      central neural mechanisms of pain relief from capsaicin-elicited heat
      hyperalgesia by administering cold stimuli. We hypothesized that cooling might
      facilitate endogenous descending inhibitory mechanisms. We compared
      intraindividual neural responses of 15 healthy male volunteers to cold (20, 0
      degrees C), intermediate (30 degrees C) and heat stimuli (43 degrees C) on
      untreated vs. capsaicin-treated skin using event-related fMRI in a 2 x 4
      factorial design. Thermal stimuli were applied at the right hand in two separate
      imaging sessions using a Peltier-element. Psychophysical ratings of the perceived
      valence and intensity (VAS: 1-100) were obtained after each stimulus. The 43
      degrees C-stimulus was perceived as excessively painful on capsaicin-treated skin
      as opposed to an unpleasant sensation on normal skin. In contrast, the 0 degrees
      C-stimulus was perceived unpleasant when applied on untreated skin while subjects
      rated the same stimulus pleasant in the capsaicin-treated condition. When neural
      responses to the 0 degrees C-stimulus were compared between the untreated and
      capsaicin-treated skin condition there were stronger BOLD-responses in prefrontal
      cortex (PFC) and periaqueductal grey (PAG) which correlated with increasing
      perceived pleasantness (VAS). Based on a connectivity analysis which identified
      cold-dependent contributions of PFC activity with PAG in heat-hyperalgesia we
      propose that cold-induced pain relief partly results from activation of
      endogenous descending inhibition of nociception. The data illustrate that
      perception of nociceptive input may largely be determined by competing aversive
      appetitive motivational states.

PMID- 18614291
TI  - Intranasal anticonvulsive treatment: a prospective management of intractable
      epilepsy?
AB  - As a common human disorder, epilepsy affects about 0.5% of the population. In
      many patients with epilepsy, seizures are well-controlled with currently
      available anti-epileptic drugs, but around 35% of patients with epilepsy continue
      to have seizures despite carefully optimized drug treatment. Recently, intrinsic
      or acquired overexpression of multidrug transporters in the blood-brain barrier
      has been suggested to result in producing pharmacoresistance in epilepsy, for
      anti-epileptic drugs concentrations would be reduced to the level that is
      insufficient to cause anti-epileptic activity. Intranasal administration provides
      a direct transport pathway to brain tissue that circumvents the blood-brain
      barrier for many drugs and neuropeptides. These significant conditions support
      the hypothesis that intranasal anticonvulsive treatment may be a prospective
      management of intractable epilepsy. Unfortunately, there are few studies on
      intranasal anticonvulsive treatment conducted in the field of intractable
      epilepsy. Our hypothesis provides not only a new alternative treatment for
      intractable epilepsy but also has potential for investigating the mechanisms
      underlying the development of pharmacoresistance in epilepsy.

PMID- 18614292
TI  - Induced hypothermia as a new approach to bronchopulmonary dysplasia.

PMID- 18614293
TI  - How to prevent immunological reactions in leprosy patients and interrupt
      transmission of Mycobacterium leprae to healthy subjects: two hypotheses.
AB  - The basis of World Health Organization strategy for leprosy elimination is that
      the only source and reservoir for infection are patients with the disease. It was
      assumed that multi drug therapy (MDT) would reduce transmission of Mycobacterium
      leprae, but there is no convincing evidence for this. Furthermore, even if MDT
      has been proved to be extremely effective against the infectious disease, a
      noticeable proportion of leprosy patients can suffer from immunologic
      hypersensitivity reactions which are now the most significant issue in the
      managements of the disease. In endemic areas it was found that: M. leprae
      survives outside human body; healthy individuals harbor M. leprae bacilli in
      nasal cavity and shed micro-organisms in environment; there is widespread
      subclinical transmission of M. leprae with transient infection of the nose
      resulting in the development of a mucosal immune response. This disparate
      clinical, epidemiologic, and microbiologic evidence leads to the first
      hypothesis: that antigenic load in local tissues, sufficient to trigger the
      immune response, comes from external supply of M. leprae organisms. The
      hypothiocyanite anion (OSCN-) is generated in vivo by the reaction of thiocyanate
      with hydrogen peroxide catalyzed by lactoperoxidase. OSCN- is an antimicrobial
      oxidizing agent that prevents growth of bacteria, fungi, and viruses. OSNC-
      exists in lower airway secretions and lung has never been reported to be affected
      by leprosy. There is a sufficient concentration of OSCN- in the saliva, and
      accordingly mouth is rarely affected by leprosy. By contrast, the concentration
      of this compound is low or nil in nasal and lacrimal secretions and leprosy very
      often affects nose and eyes. The second hypothesis is that OSCN- may also protect
      from leprosy. Recently a method of OSCN- production, not involving enzymatic
      steps or use of toxic heavy-metal salts, has been patented. Studies on the
      susceptibility of M. leprae to hypothiocyanite could be carried out and, in case
      of positive results, the substance might be used in order to sterilize the nasal
      cavity of healthy carriers and prevent transmission of M. leprae to healthy
      subjects and to leprosy patients in whom it may trigger an immune response.

PMID- 18614294
TI  - Keloid and hypertrophic scarring may result from a mechanoreceptor or
      mechanosensitive nociceptor disorder.
AB  - Keloid and hypertrophic scars (HSs) are fibroproliferative diseases (FPDs) of the
      skin. It is well known that stretching tension of skin, in other words mechanical
      force (mechanical loading, mechanical stress) on the skin, is an important factor
      that promotes their growth. Currently, the widely held view is that while
      mechanical force is a factor that aggravates keloid/HS growth after their
      induction, it is not a causative factor. However, there is no evidence that
      supports this view and recent observations from studies of keloids/HSs suggest
      that mechanical force in fact not only promotes the growth of such scars, it also
      drives their generation. Here, I hypothesize that FPDs of the skin, including
      keloids and HSs, are the result of an excessive responsiveness or functional
      failure of either dermal cell mechanoreceptors (mechanosensors) or
      mechanosensitive nociceptors of sensory fibers in the skin. In other words, FPDs
      of the skin are mechanoreceptor/mechanosensor or mechanosensitive nociceptor
      (mechanosensory) disorders, respectively. Moreover, by examining the site
      specificity of keloids, I show that stretching tension may be a major mechanical
      force that drives their generation. While further experimental studies of
      signaling pathways related to mechanotransduction, mechanosensitive (MS)
      channels, cell adhesion molecules, and cytoskeleton dynamics are needed, this
      hypothesis may provide new insights into the etiology and pathology of FPDs of
      the skin such as keloids and HSs.

PMID- 18614295
TI  - A role for neurological memory feedback loops in psychiatric depression.
AB  - This hypothesis proposes a neurological system model of memory feedback loops
      which demonstrates the difference in specific memory processing between depressed
      and non-depressed people. It is suggested that non-depressed people have a
      functioning neurological memory feedback loop system which enables them to re
      appraise and be more circumspect with given situations. In contrast to this, it
      is suggested that depressed people do not have a functioning memory feedback loop
      and it is this that leads to the deficit of circumspect and considered thinking.
      This could explain why depressed people commonly exhibit instantaneous negative
      reactions to events that pre-morbidity were considered to be pleasurable or
      interesting.

PMID- 18614296
TI  - [On the article "Syphilis et grossesse" J Gynecol Obstet Biol Reprod 2008;37,
      hors-serie 1:F29-F33].

PMID- 18614298
TI  - [Fetal pulse oximetry: clinical practice].
AB  - OBJECTIVE: To assess in current practice the application of our protocol of using
      fetal pulse oximetry during labor, to evaluate whether fetal scalp blood sampling
      can be reduced and to determinate reliability of fetal pulse oximetry on the
      prediction of poor neonatal outcomes. STUDY DESIGN: Prospective observational
      unicenter cohort including 449 patients during two years. All pregnancies were
      singleton, greater than or equal to 37 weeks' gestation, cephalic presentation,
      and had non reassuring fetal heart rate. The poor neonatal outcome was defined by
      one of the followings: arterial umbilical cord pH<or=7.15, umbilical cord base
      deficit greater than or equal to 12 mmol/l, 5 min Apgar score less than or equal
      to 7, transfer in neonatal intensive care unit, secondary respiratory distress
      and death. RESULTS: The use of fetal pulse oximetry was concordant with our
      protocol in more than 80% of cases. The frequency of fetal scalp blood sampling
      was significantly reduced from 9.9 to 8.6% after the introduction of our
      protocol. With a 30% threshold, diagnostical values of fetal oximetry for a poor
      neonatal outcome were 9.1% for sensitivity, 93.1% for specificity, 79.4% for
      negative predictive value and 25.9% for positive predictive value. With a 40%
      threshold, the diagnostic values were 74, 51.6, 88.2 and 28.9% respectively.
      CONCLUSION: The strict application of our protocol allow a less aggressive
      management of labor with a significant decrease in fetal scalp blood sampling.
      This study shows that with a 40% threshold, fetal pulse oximetry could be
      considered as a reliable tool for the management of labor with no increase of
      poor neonatal outcomes. On the other hand, the threshold which could determine
      whether an abnormal fetal heart rate needs immediate intervention still remains
      unclear.

PMID- 18614297
TI  - [Painful perineum in all its forms. Contribution of manual medicine and
      osteopathy. Clinical study].
AB  - No satisfactory therapy has yet been found to relieve many chronic pelviperineal
      pains such as Dyspareunia, Vulvodynia, Coccygodynia and other various pelvic
      pains, although these can be highly disruptive in everyday life. They may be
      brought on by an osteo-myo-fascial disorder, often undetected despite the
      possibility to effectively treat, this condition using manual medicine in the
      gynaecologist's office. A framed clinical examination protocol as well as a
      therapeutic one are offered in this novel approach still rarely implemented in
      gynaecology. Such treatment is documented in six typical clinical cases and a
      global study on 86 patients with disruptive chronic pelviperineal pain, showing
      71% satisfactory results following two manual medicine sessions. These very
      encouraging results need to be confirmed on a larger scale in order to establish
      an appropriate teaching protocol.

PMID- 18614299
TI  - Characterization of pairwise and multiple sequence alignment errors.
AB  - We characterize pairwise and multiple sequence alignment (MSA) errors by
      comparing true alignments from simulations of sequence evolution with
      reconstructed alignments. The vast majority of reconstructed alignments contain
      many errors. Error rates rapidly increase with sequence divergence, thus, for
      even intermediate degrees of sequence divergence, more than half of the columns
      of a reconstructed alignment may be expected to be erroneous. In closely related
      sequences, most errors consist of the erroneous positioning of a single indel
      event and their effect is local. As sequences diverge, errors become more complex
      as a result of the simultaneous mis-reconstruction of many indel events, and the
      lengths of the affected MSA segments increase dramatically. We found a systematic
      bias towards underestimation of the number of gaps, which leads to the
      reconstructed MSA being on average shorter than the true one. Alignment errors
      are unavoidable even when the evolutionary parameters are known in advance.
      Correct reconstruction can only be guaranteed when the likelihood of true
      alignment is uniquely optimal. However, true alignment features are very
      frequently sub-optimal or co-optimal, with the result that optimal albeit
      erroneous features are incorporated into the reconstructed MSA. Progressive MSA
      utilizes a guide-tree in the reconstruction of MSAs. The quality of the guide
      tree was found to affect MSA error levels only marginally.

PMID- 18614300
TI  - A meta-analysis on experimental infections with porcine circovirus type 2 (PCV2).
AB  - A meta-analysis was performed with the aim to identify factors with a relevant
      influence on the expression of clinical postweaning multisystemic wasting
      syndrome (PMWS) under experimental conditions. Data from 44 studies were included
      in the analysis. Several variables were studied: number of pigs in the
      experiment, intake of colostrum, serological status against porcine circovirus
      type 2 (PCV2), strain of PCV2 used for inoculation, the route and dose of
      inoculation, and use of potential triggering factors (such as co-infections,
      vaccinations, or immunomodulator products). Multiple correspondence analysis and
      log-linear regression methods were used to establish the relationships between
      the studied variables and the number of PCV2 infected pigs that developed PMWS.
      Based on the results of the meta-analysis, the most successful animal experiment
      aimed to develop PMWS should include: (1) colostrum-deprived pigs, (2) age of
      inoculation below 3 weeks, (3) high doses of PCV2 inoculum, (4) PCV2 strain from
      genotype 1, and (5) co-infection with another swine pathogen as a triggering
      factor.

PMID- 18614301
TI  - Neurological examination of preterm infants at term equivalent age.
AB  - BACKGROUND: We previously reported the neurological findings of the Dubowitz
      neonatal examination in a cohort of 157 low-risk preterms born between 25 and 33
      weeks gestational age (GA) and examined at term equivalent age (TEA). Median and
      range of scores were wider than those found in term-born infants and preterms
      showed a different neurological behaviour in specific items. However, the cohort
      number was too small to draw any definitive conclusion about the distribution of
      findings. AIMS: We provide normative data from a low-risk cohort of 380 preterm
      infants; we also assess the findings and their relationship to motor outcome in
      preterms with major cranial ultrasound (US) abnormality. STUDY DESIGN: We
      assessed, at TEA, 380 low-risk preterms born <35 weeks gestation (range 25-34.9,
      median 29) with normal 2 year motor outcome and 85 preterm infants with major US
      abnormality. RESULTS: At TEA low-risk preterms had less flexor limb tone, poorer
      head control but better visual following than term-born infants. For 28/34 of the
      neurological items the range and median scores were similar across gestational
      ages. In infants with major US lesions the range and median scores differed from
      low-risk preterms in 20/34 items; 40% of infants developing a diplegia and 80%
      developing a tetraplegia had >7 items outside the 90th centile; all infants with
      >12 items outside the 90th centile developed a tetraplegia. CONCLUSIONS: We
      provide reference values for the neurological examination of low-risk preterms at
      TEA. In infants with major US abnormality the number of items outside the 90th
      centile was an indicator of outcome severity.

PMID- 18614302
TI  - Porcine Aurora A accelerates Cyclin B and Mos synthesis and promotes meiotic
      resumption of porcine oocytes.
AB  - Full-grown oocytes arrested at germinal vesicle stage contain many dormant
      maternal mRNAs, and Aurora A has been reported to play a key role for the
      translation of these maternal mRNAs in Xenopus oocytes. Although the presence of
      Aurora A has been reported in mammals, the functions of Aurora A on the protein
      synthesis and the meiotic resumption have never been elucidated in mammalian
      oocytes. In the present study, the effects of porcine Aurora A on meiotic
      resumption of porcine oocytes were examined. At first, we cloned porcine Aurora A
      from total RNA of immature porcine oocytes by RT-PCR and obtained full-length
      cDNA that was 77%, 86% and 54% homologous with mouse, human and Xenopus Aurora A,
      respectively. The Aurora A mRNA and large amounts of protein were present
      throughout maturation period in porcine oocytes. The overexpression of porcine
      Aurora A by the mRNA injection into immature porcine oocytes had no effects on
      Cyclin B synthesis and meiotic resumption. Therefore we constructed a mutated
      Aurora A (AA-Aurora A), which was replaced the expecting inhibitory
      phosphorylation sites, serines 283 and 284, to non-phosphorylatable alanines. The
      oocytes expressed AA-Aurora A were accelerated their Cyclin B synthesis and Rsk
      phosphorylation, an indicator of Mos synthesis, then their meiotic resumption was
      promoted significantly. These results suggest for the first time in mammalian
      oocytes that mammalian Aurora A stimulates the protein synthesis and promotes the
      meiotic resumption. In addition, we identified the inhibitory phosphorylation
      sites of porcine Aurora A, and indicate the presence of phosphorylation-dependent
      regulation mechanisms in mammalian Aurora A.

PMID- 18614303
TI  - Biopharmaceutics classification systems for new molecular entities (BCS-NMEs) and
      marketed drugs (BCS-MD): theoretical basis and practical examples.
AB  - The aim of this work is to develop biopharmaceutics classification systems for
      new molecular entities (BCS-NMEs) and marketed drugs (BCS-MD). The kinetics of
      gastrointestinal (GI) wall permeation and dissolution were re-considered
      theoretically. The relationships between the solubility/dose ratio and the
      fractions of dose dissolved and absorbed, were also examined. Mean time
      calculations for drug dissolution (MDT) and permeation (MPT) of the GI wall were
      analyzed in respect to the mean intestinal transit time (MITT) to identify a
      cutoff point for drug dissolution and GI wall permeation. Dissolution experiments
      for marketed drugs were carried out. NMEs were classified into four classes of
      BCS-NMEs, based on solubility/dose ratio and apparent permeability estimates. A
      physiologically based cutoff time point for dissolution and permeation was used
      to differentiate rapidly from slowly dissolving-permeating marketed drugs, which
      were classified into four classes of BCS-MD using their dissolution index
      (DI=MITT/MDT) and permeation index (PI=MITT/MPT) values as follows: I (DI>or=3,
      PI>or=3), II (DI<3, PI>or=3), III (DI>or=3, PI<3) and IV (DI<3, PI<3). In
      conclusion, two classification systems were developed, one for NMEs based on
      solubility/dose ratio and permeability estimates and one for marketed drugs based
      on MDT and MPT estimates.

PMID- 18614304
TI  - A solitary fibrous tumor arising in the parapharyngeal space, with MRI and FDG
      PET findings.
AB  - We present the imaging and pathological features of a 38-year-old man in whom a
      large parapharyngeal solitary fibrous tumor (SFT) on the left side was found. On
      MRI, the tumor showed a nodule-in-nodule appearance. The inner nodule revealed
      high signal intensities both on T1- and T2-weighted MR images. The entire tumor
      showed heterogeneous enhancement on gadolinium-enhanced T1-weighted images. (18)F
      fluorodeoxyglucose (FDG) positron emission tomography (PET) identified
      heterogeneous radiotracer uptake of FDG in the inner nodule of the tumor.
      Histologic examinations revealed an admixture of growth patterns, including a
      "patternless pattern" and "haemangiopericytoma-like pattern". The tumor was
      positive for CD34. Imaging features of SFT arising in the parapharyngeal space
      are discussed with a review of literatures. This is the first report of FDG-PET
      finding of SFT arising in the head and neck. More cases are needed to achieve
      diagnostic significance from FDG-PET findings of parapharyngeal SFTs.

PMID- 18614305
TI  - Undifferentiated sarcoma of the maxillary sinus: report of a rare case in an
      adult.
AB  - A 51-year-old man complained of left facial swelling and recurrent nasal
      bleeding. A giant solid tumor in the left maxillary sinus was detected on head CT
      and MRI, and this tumor was destroying the maxilla and extending into the orbit,
      pterygoid muscle and posterior paranasal sinuses. The resected specimen consisted
      of spindle cells containing necrotic material. Histological examination revealed
      immature tumor cells, and immunohistological study of the tumor showed staining
      was only positive for vimentin. We accordingly diagnosed undifferentiated sarcoma
      in the maxillary sinus. Combination chemotherapy with vincristine, doxorubicin,
      cyclophosphamide/ifosfamide with mesna and etoposide was administered; however,
      the tumor was unresponsive and the patient died after around 3 months.

PMID- 18614307
TI  - Tinnitus after cochlear implantation.
AB  - OBJECTIVE: The purpose of this study was to investigate properties of tinnitus
      which starts after cochlear implantation. Of the 17 adult patients in our
      cochlear implant group, four (23.5%) who had no pre-implantation tinnitus were
      eligible for the study. METHODS: Each patient was requested to complete a short
      questionnaire regarding his or her experience with tinnitus. Tinnitus match test
      was performed for each patient by using an Interacoustic Clinical Audiometer
      (model AC40; Assens, Denmark). RESULTS: Tinnitus match test revealed a tinnitus
      frequency of a 4KHz for three and of a 6KHz for one patient. Mean value of the
      loudness score was calculated as 17.5dB SL. CONCLUSIONS: The results of this
      study emphasize the importance of counseling patients regarding risks of tinnitus
      after cochlear implantation.

PMID- 18614306
TI  - Vestibular type of Mondini anomalies with BPPV and Meniere's disease-like
      symptoms.
AB  - An extremely rare case with labyrinthine anomaly with normal hearing was
      demonstrated. This case firstly showed transient positioning vertigo like benign
      paroxysmal positional vertigo (BPPV) and subsequently episodic vertigo like
      Meniere's disease. A 55-year-old male attended our hospital, complaining of
      transient but persistent positioning vertigo in 2004. The apogeotropic
      positioning nystagmus was observed in spine position. In 2005, he came to feel
      episodic vertigo continuously for more than 30min like Meniere's disease. We
      examined CT scan and 3D-MRI, indicating the hypoplastic lateral semicircular
      canal (L-SCC) fused together with enlarged vestibule on the left side. We finally
      diagnosed this case as Mondini anomaly on the left side. The imaging analysis is
      the most useful for differential diagnosis of Mondini anomalies, because symptoms
      in these patients are actually various due to the individual inner ear condition.
      The mechanism of generation of BPPV-like vertigo: the otolith in deformed utricle
      might be transferred into the fused space with vestibule and L-SCC, resulting in
      the irrigation of the hypoplastic cupula. The mechanism of generation of
      Meniere's disease-like vertigo: neuro-otologic findings with furosemide test
      implied endolymphatic hydrops on the left side. Meniere's disease-like episodic
      vertigo could be due to subsequently generated endolymphatic hydrops.

PMID- 18614308
TI  - [Refractory ascites in patients with cirrhosis].

PMID- 18614309
TI  - Comparison of MRI fast SPGR single slice scan and continuous dynamic scan in
      patients with obstructive sleep apnea-hypopnea syndrome.
AB  - OBJECTIVE: To evaluate the application value of MRI fast SPGR single slice scan
      in patients with obstructive sleep apnea-hypopnea syndrome when comparing the
      images between fast SPGR single slice scan and continuous dynamic scan. METHODS:
      Eighteen patients with obstructive sleep apnea-hypopnea syndrome were examined by
      fast SPGR single slice scan and continuous dynamic scan in turn. Fast SPGR single
      slice scans were conducted when the phases of apnea, inspiration and expiration
      appeared on the respiratory wave of the subjects. Fast SPGR continuous dynamic
      scans were conducted when the patients were awake and apneic. The scan planes
      were median sagittal plane and axial planes (the slice of middle part of palate,
      the slice of inferior part of palate, the slice of middle part of lingual root
      and the slice of 0.5cm beneath the free margin of epiglottis). The obstructed
      sites and the cross-sectional areas of upper airway were compared between the two
      scan methods. RESULTS: Seven cases showed complete obstruction at the narrowest
      sites of upper airway when apnea appeared; eleven cases showed marked decrease in
      cross-sectional areas at the narrowest sites compared with the areas when the
      patients were awake; two cases manifested multiple narrowness. The obstructed
      sites showed by the two scan methods were same. The difference of the cross
      sectional areas of upper airway between the two scan methods was insignificant
      (P>0.05). CONCLUSION: Fast SPGR single slice scan can accurately reflect the
      obstructed sites of upper airway when the breath breaks off and is the
      complementary method of continuous dynamic scan. Sometimes, single slice scan can
      replace continuous dynamic scan.

PMID- 18614311
TI  - Update: Complications and management of infrarenal EVAR.
AB  - Endovascular aortic aneurysm repair (EVAR) is now an established technique for
      treating many patients with infrarenal abdominal aortic aneurysm. Familiarity
      with the complications associated with this technique and understanding treatment
      options are crucial for the lifelong performance of stent graft. This pictorial
      review article describes the currant role of different imaging modalities in
      surveillance and discusses the complications and its management strategies.

PMID- 18614310
TI  - Elemental distribution mapping on breast tissue samples.
AB  - The main of this work is to determine the elemental and absorption distribution
      map in breast tissue samples by X-ray fluorescence and X-ray transmission
      microtomography. The experiments were performed at the X-ray fluorescence
      beamline (D09B-XRF) in the Brazilian Synchrotron Light Source (LNLS), Campinas,
      Brazil. A quasi-monochromatic beam produced by a multilayer monochromator was
      used as an incident beam. The sample was placed on a high precision goniometer
      and translation stages that allow rotating as well as translating it
      perpendicularly to the beam. The fluorescence photons were collected with an
      energy dispersive HPGe detector placed at 90 degrees to the incident beam, while
      transmitted photons were detected with a fast Na(Tl) scintillation counter ()
      placed behind the sample on the beam direction. All the tomographic images were
      reconstructed using a filtered-back projection algorithm. In the breast tissue
      samples, it was possible to determine the distribution of Zn, Cu and Fe in
      healthy tissue and tumor.

PMID- 18614312
TI  - Memory and survival after microbeam radiation therapy.
AB  - BACKGROUND: Disturbances of memory function are frequently observed in patients
      with malignant brain tumours and as adverse effects after radiotherapy to the
      brain. Experiments in small animal models of malignant brain tumour using
      synchrotron-based microbeam radiation therapy (MRT) have shown a promising
      prolongation of survival times. MATERIALS AND METHODS: Two animal models of
      malignant brain tumour were used to study survival and memory development after
      MRT. Thirteen days after implantation of tumour cells, animals were submitted to
      MRT either with or without adjuvant therapy (buthionine-SR-sulfoximine=BSO or
      glutamine). We used two orthogonal 1-cm wide arrays of 50 microplanar
      quasiparallel microbeams of 25 microm width and a center-to-center distance of
      about 200 microm, created by a multislit collimator, with a skin entrance dose of
      350 Gy for each direction. Object recognition tests were performed at day 13
      after tumour cell implantation and in monthly intervals up to 1 year after tumour
      cell implantation. RESULTS: In both animal models, MRT with and without adjuvant
      therapy significantly increased survival times. BSO had detrimental effects on
      memory function early after therapy, while administration of glutamine resulted
      in improved memory.

PMID- 18614313
TI  - Bone diagnosis by X-ray techniques.
AB  - In this work, two X-ray techniques used were 3D microcomputed tomography (micro
      CT) and X-ray microfluorescence (micro-XRF) in order to investigate the internal
      structure of the bone samples. Those two techniques work together, e.g. as a
      complement to each other, to characterize bones structure and composition.
      Initially, the specimens were used to do the scan procedure in the microcomputer
      tomography system and the second step consists of doing the X-ray
      microfluorescence analysis. The results show that both techniques are powerful
      methods for analyzing, inspecting and characterizing bone samples: they are
      alternative procedures for examining bone structures and compositions and they
      are complementary.

PMID- 18614314
TI  - USAXS and SAXS from cancer-bearing breast tissue samples.
AB  - USAXS and SAXS patterns from cancer-bearing human breast tissue samples were
      recorded at beamline ID02 of the ESRF using a Bonse-Hart camera and a pinhole
      camera. The samples were classified as being ductal carcinoma, grade II, and
      ductal carcinoma in situ, partly invasive. The samples included areas of healthy
      collagen, invaded collagen, necrotic ducts with calcifications, and adipose
      tissue. The scattering patterns were analyzed in different ways to separate the
      scattering contribution and the direct beam from the observed rocking curve (RC)
      of the analyzer. It was found that USAXS from all tissues was weak, and the
      effects on the analyzer RC were observed only in the low-intensity tails of the
      patterns. The intrinsic RC was convolved with different model functions for the
      impulse response of the sample, and the best fit with experiment was obtained by
      the Pearson VII function. Significantly different distributions for the Pearson
      exponent m were obtained in benign and malignant regions of the samples. For a
      comparison with analyzer-based imaging (ABI) or diffraction enhanced imaging
      (DEI) a "long-slit" integration of the patterns was performed, and this
      emphasized the scattering contribution in the tails of the rocking curve.

PMID- 18614315
TI  - Newly defined in vitro quality control ranges for oritavancin broth microdilution
      testing and impact of variation in testing parameters.
AB  - A 9-laboratory M23-A2 quality control (QC) study was performed to evaluate
      reproducibility of oritavancin MICs against reference strains of Staphylococcus
      aureus, Enterococcus faecalis, and Streptococcus pneumoniae using broth
      microdilution assays in the presence of polysorbate 80. Polysorbate 80 has
      previously been shown to be required for accurate measurement of oritavancin
      broth microdilution MICs. Greater than 95% of replicate results (n =
      270/organism) fell within the following QC ranges (in micrograms per milliliter):
      S. aureus ATCC 29213, 0.015 to 0.12; E. faecalis ATCC 29212, 0.008 to 0.03; and
      S. pneumoniae ATCC 49619, 0.001 to 0.004. Oritavancin MIC QC ranges were, thus,
      narrow and reproducible. Parameters affecting testing results in the presence of
      polysorbate 80 were also evaluated. Oritavancin MICs were equivalent to or within
      1 doubling dilution of those obtained under standard Clinical and Laboratory
      Standards Institute testing conditions, regardless of incubation time (18, 24, or
      48 h), Ca(2+) concentration, pH, or frozen panel storage time (up to 6 months).

PMID- 18614316
TI  - Emphysematous pyelonephritis with emphysematous pancreatitis.

PMID- 18614317
TI  - Lumbosacral plexopathy due to common iliac artery aneurysm misdiagnosed as
      intervertebral disc herniation.
AB  - We report a case of lumbosacral plexopathy caused by an isolated aneurysm in the
      common iliac artery. The patient presented with low back and buttock pain
      radiating to the right leg and numbness in the L5 and S1 dermatomes. A computed
      tomography scan showed an aneurysm of the right common iliac artery. This case
      serves to increase awareness of the possibility of lumbosacral plexopathy in
      patients with symptoms of a prolapsed intervertebral disc.

PMID- 18614318
TI  - Stevens-Johnson syndrome after mycoplasma pneumoniae infection.

PMID- 18614319
TI  - Point-of-care testing at triage decreases time to lactate level in septic
      patients.
AB  - Early recognition of elevated lactate levels may hasten the detection of time
      sensitive illness. We studied a method to measure lactate levels in septic
      patients using a point-of-care (POC) device at Emergency Department triage. A
      convenience sample of adult patients with sepsis was enrolled. Consenting
      patients received a fingertip lactate measurement using a POC device. Treating
      clinicians were blinded to study and POC test results. Whole blood lactate levels
      were drawn at the discretion of the treating physician. A total of 238 patients
      were eligible; 154 (65%) consented, 5 left without treatment after consenting. Of
      the remaining 149, 44 (30%) patients received both POC and whole blood lactates.
      Median time from triage to POC lactate result was 21 min (interquartile range
      [IQR] 14-25). Median time from triage to whole blood lactate result was 172 min
      (IQR 119-256). The time difference between POC test result and whole blood
      lactate result was 151 min (IQR 101-247). Triage POC fingertip lactate is a
      feasible method for reducing time to identification of lactate levels in patients
      with sepsis. Larger studies are needed to determine the ability of POC lactate
      measurement to aid in the risk stratification of septic patients.

PMID- 18614320
TI  - An unusual upper airway foreign body.

PMID- 18614321
TI  - Whole bowel irrigation and the hemodynamically unstable calcium channel blocker
      overdose: primum non nocere.
AB  - Sustained-release calcium channel blocker (CCB SR) overdoses are potentially life
      threatening ingestions. These patients may not become hemodynamically unstable
      until many hours after ingestion. On theoretical grounds, some have suggested
      that whole bowel irrigation (WBI) with polyethylene glycol electrolyte lavage
      solution may be of value in the management of these cases. We report two cases
      with poor outcome (including one fatality) that were complicated by the use of
      WBI. Both cases were treated with WBI beginning before and continuing after
      developing hypotension. WBI should be avoided in the setting of the
      hemodynamically unstable CCB SR overdose.

PMID- 18614322
TI  - Emergency ultrasound in cervical ectopic pregnancy.

PMID- 18614323
TI  - Cerebral venous thrombosis.

PMID- 18614324
TI  - The mangled extremity.
AB  - The management of patients with severe extremity injuries involves focused
      efforts at limb salvage and mitigation of potential infectious complications. An
      in-depth understanding of the proper approach to initial management is essential,
      as it may impact eventual outcome. The use of established scoring systems may
      predict those at greater risk and enable expeditious utilization of appropriate
      consultation services. This case-based review highlights critical aspects of
      patient care and provides a framework for the role of the Emergency Physician.

PMID- 18614325
TI  - Left ventricular bullet embolus: a case report and review of the literature.
AB  - Missile embolization to the heart occurs infrequently in penetrating trauma. The
      lack of a concentrated experience at any single institution contributes to the
      controversies pertaining to diagnostic and therapeutic approaches to management.
      The objective of this study was to describe a case of a left ventricular bullet
      embolus and provide a detailed diagnostic and therapeutic framework for
      management of intracardiac projectiles. Initial management of a patient with
      suspected intracardiac projectiles is dictated by his or her hemodynamic status.
      Unstable patients generally require operative intervention. In the stable
      patient, associated injuries must be sought. Localization of the projectile can
      be aided by echocardiogram, fluoroscopy, or angiography. Definitive management is
      individualized, and can range from observation to percutaneous or operative
      extraction. The decision depends on the cardiac chamber involved, the patients'
      symptoms, and the projectile's size, shape, and location within the chamber.
      Missile embolus to the heart is an infrequent occurrence, but when found presents
      a diagnostic and therapeutic challenge. Management strategies should be
      individualized. A detailed management algorithm is provided.

PMID- 18614326
TI  - Ruptured abdominal aortic aneurysm presenting as painless testicular ecchymosis:
      the scrotal sign of Bryant revisited.
AB  - The diagnosis of ruptured abdominal aortic aneurysm (AAA) is often missed as a
      result of an atypical presentation, resulting in increased mortality. Here we
      present an unusual case of painless scrotal ecchymosis as a presentation of
      ruptured AAA. We review the origin of the scrotal sign of Bryant and emphasize
      the importance of this uncommon finding as a diagnostic aid in atypical cases of
      ruptured AAA.

PMID- 18614327
TI  - Ultrasound can accurately guide gastrostomy tube replacement and confirm proper
      tube placement at the bedside.
AB  - BACKGROUND: Malfunctioning or dislodged gastrostomy tubes (G-tubes) often require
      urgent replacement and reinsertion in the Emergency Department (ED). Few data
      exist regarding the best technique for bedside catheter replacement and
      verification, and individual operator preferences vary. Although a few reports
      have described the use of ultrasound guidance during the initial percutaneous
      insertion, no data are available concerning its role during subsequent G-tube
      replacements. OBJECTIVE: We sought to investigate the utility of bedside
      ultrasonography during G-tube replacements in the ED. METHODS: This was a
      prospective pilot study conducted at a Level 1 Trauma Center with an annual
      census of 90,000 patients. Seven adults and three children with malfunctioning G
      tubes were enrolled. Three tubes were cracked and leaking, and seven tubes had
      been dislodged. Under ultrasound, a new G-tube was inserted through the
      previously fashioned tract. After insertion, color Doppler was applied over the
      catheter tip to enhance visualization during gentle tube oscillation. RESULTS:
      Ultrasound successfully visualized G-tube replacement in all 10 patients.
      Application of color Doppler over the G-tube tip during catheter oscillation
      enhanced placement confirmation. Sonographic findings were corroborated with
      gastric content aspiration, contrast-enhanced radiographs, and successful use of
      the new G-tubes. No false tracts were identified during ultrasound-guided
      insertion, post-procedure sonographic confirmation, or subsequent radiographs.
      CONCLUSION: The improper replacement of a G-tube can lead to devastating
      consequences. Verifying appropriate placement through aspirate evaluation can be
      misleading, and post-procedure radiographs increase radiation exposure and ED
      wait times. Bedside ultrasonography can be used to guide catheter insertion while
      providing a safe and quick adjunct to confirm proper G-tube placement.

PMID- 18614328
TI  - Eschar with cellulitis as a clinical predictor in community-acquired methicillin
      resistant Staphylococcus aureus (MRSA) skin abscess.
AB  - This study was designed to determine the validity of a central eschar with
      surrounding cellulitis as a clinical predictor for CA-MRSA infection. In this 10
      month prospective observational study, patients with a chief complaint or
      clinical findings of skin infection with abscess had study data sheets placed on
      their chart. All abscesses were treated with incision and drainage, and wound
      cultures were obtained. Exclusionary criteria included patient age under 18
      years, recently incarcerated within 14 days, and hospitalized or in a nursing
      home within 10 days. Correlation of wound culture results with recorded physical
      examination determined the sensitivity, specificity, and positive/negative
      predictive values. A total of 224 patients with abscesses were enrolled; 18
      patients met exclusion criteria. An additional 78 patients were excluded because
      no wound cultures had been obtained, study data form was incomplete, or there was
      no evidence of wound cellulitis. Of the 128 remaining patients, 91 wound cultures
      grew MRSA (71% prevalence). Of these 91 cases, 50 tested positive for central
      black eschar, yielding a sensitivity of 55% (95% confidence interval [CI] 0.45
      0.65). Thirty-seven patients had abscesses that grew non-MRSA bacteria. Three of
      these were positive for central black eschar, yielding a specificity of 92% (95%
      CI 0.83-1.01). The positive predictive value was 94% (95% CI 0.88-1.01) and the
      negative predictive value was 45% (95% CI 0.32-0.59). A central black eschar with
      cellulitis has good specificity and high positive predictive value in diagnosing
      CA-MRSA infection.

PMID- 18614329
TI  - [Effects of sedative agents on metabolic demand].
AB  - Literature about the effects of sedative drugs on the metabolic demand of
      critically ill patients is relatively old and of relatively poor quality. Most
      are experimental or observational studies. Level of evidence is therefore
      relatively low corresponding to "expert opinion". The effects of analgesics and
      hypnotics on tissue metabolic demand associated remain difficult to be adequately
      quantified. They are essentially related to a decreased neuro-humoral response to
      stress. This response involves principally the sympathetic system, which could be
      effectively blocked by most of the anesthetic agents. Other factors could
      participate to the observed reduction in tissue metabolic demand, as a decrease
      in spontaneous muscular activity, a reduction in work of breathing and/or a
      decrease in body temperature. The relative contribution of these different
      factors will depend on the clinical situation of the patient. Proper effects of
      anesthetic agents on cellular metabolism are limited as they can only decrease
      the functional component of this metabolism especially at the level of the heart
      and to some extent, at the level of the brain. Although the control of the
      sympathetic activity may be beneficial in critically ill patient, complete
      sympathetic blockade could be detrimental. Indeed, when oxygen transport to the
      tissues is acutely reduced, the sympathetic system plays an important role in the
      redistribution of blood flow according of local metabolic demand. The complete
      blunting of the neuro-humoral response to stress and therefore of the sympathetic
      system alters this physiological mechanism and results in a decrease in tissue
      oxygen extraction capabilities. An imbalance between tissue oxygen demand and
      delivery could appear with the development of cellular hypoxia. The institution
      of sedation in a critically ill patient requires careful evaluation of the
      sedation level using an appropriate scale. In patients in whom a reduction in
      metabolic demand is specifically requested, but also in patients with limited
      oxygen transport, the effects of sedative agents on the oxygen consumption-oxygen
      delivery relationship must also be monitored. The choice of the different agents
      to be administered will depend on the predefined objectives. As far as
      intravenous agents are concerned, there is no evidence than one association is
      more efficient in reducing patient's metabolic demand.

PMID- 18614330
TI  - [Sedation and analgesia in the paediatric intensive care unit].
AB  - Sedation and analgesia are a constant challenging issue in paediatric intensive
      care units, for ethical reasons among others. Basically, goals and available
      treatments in that context do not differ from those in adults. For instance,
      while we propose midazolam as the first choice benzodiazepine, there is no
      evidence for encouraging the use of one morphinomimetic rather than others in
      children. On the other hand, numerous paediatric specificities do exist:
      understanding and expression of pain both different and difficult, presence and
      involvement of the parents, pain assessment methods, pharmacology, pathologies.
      It is therefore mandatory to know these specificities to ensure a proper use of
      evaluation tools and therapeutics. The paucity of strong evidence from the
      literature does not allow producing definitive consensus guidelines. However,
      some practices can be highlighted such as the use of written protocol on
      pain/sedation evaluation and therapeutics adapted to children, literature data
      and local habits, the training of medical/nursing staff and the constitution of
      local referring team. A particular attention should be paid to propofol: its use
      longer than several hours should be strongly discouraged in infants and children
      due to the risk of Propofol Infusion Syndrome. Further clinical studies should be
      conducted in an attempt to provide answers to routine, daily issues and
      questions, for example, how to tailor the level of sedation to the needs of the
      patient, how to stop it, which drug must be preferred or what place for non
      pharmacological approaches.

PMID- 18614331
TI  - A disruption of ctpA encoding carboxy-terminal protease attenuates Burkholderia
      mallei and induces partial protection in CD1 mice.
AB  - Burkholderia mallei is the etiologic agent of glanders in solipeds (horses, mules
      and donkeys), and incidentally in carnivores and humans. Little is known about
      the molecular mechanisms of B. mallei pathogenesis. The putative carboxy-terminal
      processing protease (CtpA) of B. mallei is a member of a novel family of
      endoproteases involved in the maturation of proteins destined for the cell
      envelope. All species and isolates of Burkholderia carry a highly conserved copy
      of ctpA. We studied the involvement of CtpA on growth, cell morphology,
      persistence, and pathogenicity of B. mallei. A sucrose-resistant strain of B.
      mallei was constructed by deleting a major portion of the sacB gene of the wild
      type strain ATCC 23344 by gene replacement, and designated as strain
      23344DeltasacB. A portion of the ctpA gene (encoding CtpA) of strain
      23344DeltasacB was deleted by gene replacement to generate strain
      23344DeltasacBDeltactpA. In contrast to the wild type ATCC 23344 or the sacB
      mutant 23344DeltasacB, the ctpA mutant 23344DeltasacBDeltactpA displayed altered
      cell morphologies with partially or fully disintegrated cell envelopes.
      Furthermore, relative to the wild type, the ctpA mutant displayed slower growth
      in vitro and less ability to survive in J774.2 murine macrophages. The expression
      of mRNA of adtA, the gene downstream of ctpA was similar among the three strains
      suggesting that disruption of ctpA did not induce any polar effects. As with the
      wild type or the sacB mutant, the ctpA mutant exhibited a dose-dependent
      lethality when inoculated intraperitoneally into CD1 mice. The CD1 mice
      inoculated with a non-lethal dose of the ctpA mutant produced specific serum
      immunoglobulins IgG1 and IgG2a and were partially protected against challenge
      with wild type B. mallei ATCC 23344. These findings suggest that CtpA regulates
      in vitro growth, cell morphology and intracellular survival of B. mallei, and a
      ctpA mutant protects CD1 mice against glanders.

PMID- 18614332
TI  - Partial characterization of deltamethrin metabolism catalyzed by chymotrypsin.
AB  - Deltamethrin degradation was assessed by measuring deltamethrin reduction with GC
      MS and UV-Vis spectrophotometry following incubation of various concentrations
      (4.96-24.80 microM) of deltamethrin with alpha-chymotrypsin from bovine pancreas.
      The retention times of crude products of deltamethrin metabolic reactions were
      37.968 min, 37.415 min, 36.490 min, and 35.895 min. The UV-Vis spectrophotometric
      peak absorbance of deltamethrin was at 264 nm, and the peak absorbance of
      deltamethrin metabolic products were at 250 nm and 296 nm, respectively.
      Michaelis-Menten metabolic rate constants (V(max) and K(m)) were calculated by
      nonlinear regression for chymotrypsin using GraphPad Prism 4.0, the V(max) was
      97.97+/-26.57 nmol/L/min and K(m) was 7.84+/-3.83 microM. The larvicidal bioassay
      tests indicated that the mixture from the degradation reaction showed LC(50)
      increased significantly (P<0.05). This is the first report demonstrating
      deltamethrin metabolism by chymotrypsin.

PMID- 18614333
TI  - Biopsychosocial characteristics and neurocognitive test performance in National
      Football League players: an initial assessment.
AB  - The use of neurocognitive testing in the assessment of professional athletes
      sustaining sports-related concussions has become widespread over the past decade.
      Baseline neurocognitive testing is now a requirement for athletes in the National
      Football League (NFL). We present preliminary normative data on a computer based
      neurocognitive test (Immediate Post Concussion Assessment and Cognitive Testing;
      ImPACT) for 159 NFL athletes. Also included are summary data on basic
      biopsychosocial characteristics, including medical, psychiatric, chemical
      dependency, concussion, learning disability/attention deficit disorder, and
      symptom variables, and the relevance of each to baseline neurocognitive test
      scores.

PMID- 18614334
TI  - Neurolinguistic approach to natural language processing with applications to
      medical text analysis.
AB  - Understanding written or spoken language presumably involves spreading neural
      activation in the brain. This process may be approximated by spreading activation
      in semantic networks, providing enhanced representations that involve concepts
      not found directly in the text. The approximation of this process is of great
      practical and theoretical interest. Although activations of neural circuits
      involved in representation of words rapidly change in time snapshots of these
      activations spreading through associative networks may be captured in a vector
      model. Concepts of similar type activate larger clusters of neurons, priming
      areas in the left and right hemisphere. Analysis of recent brain imaging
      experiments shows the importance of the right hemisphere non-verbal
      clusterization. Medical ontologies enable development of a large-scale practical
      algorithm to re-create pathways of spreading neural activations. First concepts
      of specific semantic type are identified in the text, and then all related
      concepts of the same type are added to the text, providing expanded
      representations. To avoid rapid growth of the extended feature space after each
      step only the most useful features that increase document clusterization are
      retained. Short hospital discharge summaries are used to illustrate how this
      process works on a real, very noisy data. Expanded texts show significantly
      improved clustering and may be classified with much higher accuracy. Although
      better approximations to the spreading of neural activations may be devised a
      practical approach presented in this paper helps to discover pathways used by the
      brain to process specific concepts, and may be used in large-scale applications.

PMID- 18614335
TI  - Medical image analysis of 3D CT images based on extension of Haralick texture
      features.
AB  - PURPOSE: A new approach to the segmentation of 3D CT images is proposed in an
      attempt to provide texture-based segmentation of organs or disease diagnosis. 3D
      extension of Haralick texture features was studied calculating co-occurrences of
      all voxels in a small cubic region around the voxel. RESULTS: For verification,
      the proposed method was tested on a set of abdominal 3D volumes of patients.
      Statistically, the improvement in segmentation was significant for most of the
      organs considered herein. CONCLUSIONS: The proposed method has potential
      application in medical image segmentation, including diagnosis of diseases.

PMID- 18614336
TI  - Variation in the purinergic P2RX(7) receptor gene and schizophrenia.
AB  - INTRODUCTION: The purinergic receptor gene P2RX(7) is located in a major linkage
      hotspot for schizophrenia and bipolar disorders, 12q21-33. It has previously been
      associated with bipolar disorder but has never been analysed in relation to
      schizophrenia, although it is involved in several neuronal processes associated
      with schizophrenia. METHODS: Nine functionally characterised variants in P2RX(7)
      were genotyped in 389 patients diagnosed with schizophrenia, each matched on sex,
      birth-year and month with two healthy controls. RESULTS: We did not find
      association between P2RX(7) and schizophrenia and stratification on gender did
      not change this result. The high ethnic and diagnostic homogeneity of the sample
      adds credibility to this finding. CONCLUSION: P2XR(7) was not associated with
      schizophrenia in this study.

PMID- 18614337
TI  - First report of clinical and epidemiological characterisation of vancomycin
      resistant enterococci from mainland China.

PMID- 18614338
TI  - Drug utilisation 90% (DU90%) profiles of antibiotics in five Chinese children's
      hospitals (2002-2006).
AB  - This study surveyed the pattern of inpatient antibiotic use in five Chinese
      children's hospitals between 2002 and 2006, focusing on the antibiotics
      accounting for 90% of the volume utilised as well as the level of adherence to
      guidelines. The Anatomical Therapeutical Chemical Classification/Defined Daily
      Doses (ATC/DDD) and the drug utilisation 90% (DU90%) methodologies were used. In
      October 2004, national antibiotic guidelines were issued that divided antibiotics
      into non-restricted, restricted and special use grades. In five children's
      hospitals, a total of 56 different systemic antibiotics were used during the
      study period. Antibiotics that could be injected accounted for 59.0-99.8%. beta
      Lactam antibacterials (ATC codes J01C and J01D) were the most used subgroups. The
      numbers of antimicrobial agents and non-restricted antibiotics within the DU90%
      segment were 11-20 and 5-9, respectively. The proportion of non-restricted
      antibiotic consumption was ca. 40% in 2006 in four hospitals, which varied among
      hospitals during the period 2002-2005. There was considerable variation both in
      the pattern and amount of antibiotics used in the five hospitals, with
      amoxicillin/clavulanic acid, cefuroxime and cefazolin being the most commonly
      used substances. We also observed a decrease in the ranks of some restricted and
      special use antibiotics after the guidelines were issued in one hospital. The
      DU90% profiles were proven to be useful in studying the pattern of antibiotic use
      in hospitals. Finally, the study observed the effectiveness of guidelines for
      antibiotic use in some hospitals, although injectable antibiotics were widely
      used in children's hospitals in China.

PMID- 18614339
TI  - Region-dependent absorption of faropenem shared with foscarnet, a phosphate
      transporter substrate, in the rat small intestine.
AB  - Faropenem, a penem antibiotic, is orally active despite its hydrophilic nature.
      However, its intestinal absorption has not yet been characterised in detail. This
      study was undertaken to determine the factors regulating faropenem absorption
      using intestinal loops prepared in the rat duodenum, jejunum and terminal ileum.
      Faropenem disappearance was much greater than that of cefotaxime and meropenem,
      and faropenem disappeared more extensively from the terminal ileum than from the
      jejunum or duodenum. In contrast to faropenem, the disappearance of ceftibuten
      was much greater from the duodenum and jejunum than from the terminal ileum. As
      the accumulation and enzymatic degradation of faropenem was minimal in the
      intestinal mucosa, faropenem was considered to enter the portal vein smoothly
      after its disappearance from the intestinal loops. Faropenem disappearance was
      not significantly influenced by the presence of monocarboxylic acids, amino acids
      or bile acid. Dipeptides such as L-carnosine and glycylglycine slightly but
      significantly lowered faropenem disappearance from the terminal ileum. On the
      other hand, foscarnet exerted a marked inhibitory effect on faropenem
      disappearance, but the antiviral agent did not modulate ceftibuten absorption.
      The present results suggest that faropenem is in part absorbed via a phosphate
      transporter present in the rat small intestine.

PMID- 18614340
TI  - Further evidence for a functional role of the glutamate receptor gene GRM3 in
      schizophrenia.
AB  - In recent years, evidence has been accumulating indicating a major role of
      glutamate in the pathogenesis and pathophysiology of schizophrenia. Of particular
      importance in this regard are the metabotropic glutamate receptors (GRM). Thus, a
      recently published trial of the amino acid analogue LY2140023, which exerts its
      effects through the activation of the glutamate receptors GRM3/GRM2, showed an
      improvement of positive and negative symptoms comparable to treatment with
      olanzapine. A functional variant of GRM3 has been described which modulates
      synaptic glutamate levels. We assessed whether this functional variant rs6465084
      is related to schizophrenia in a large sample of patients and controls. We found
      an increased frequency of the A allele (p=0.027) and the AA genotype (p=0.024) in
      schizophrenia patients. Moreover, in an assessment of schizophrenia
      endophenotypes, patients of the AA genotype performed poorly in the digit symbol
      test, a measure of attention (p=0.008). Our results provide further evidence for
      the potential importance of the glutamate receptor GRM3 in schizophrenia, and
      indicate that the novel antipsychotic LY2140023 may actually be targeting a
      pathogenic pathway of schizophrenia.

PMID- 18614341
TI  - Binding of Ricinus communis agglutinin to a galactose-carrying polymer brush on a
      colloidal gold monolayer.
AB  - A polymer with many pendent galactose residues was prepared by atom-transfer
      radical polymerization (ATRP) of galactose-carrying vinyl monomer, 2
      lactobionamidoethyl methacrylate (LAMA), with a disulfide-carrying ATRP
      initiator, 2-(2'-bromoisobutyroyl)ethyl disulfide (DT-Br). The galactose-carrying
      polymer obtained (DT-PLAMA) was accumulated as a polymer brush via Au-S bond on a
      colloidal gold monolayer deposited on a cover glass. For comparison, a disulfide
      which carried one galactose residue at both ends (2-lactobionamidoethyl
      disulfide, Cys-Lac) was accumulated as a self-assembled monolayer (SAM) on the
      colloidal gold monolayer, too. The association and dissociation processes of
      galactose residues on the colloidal gold with a lectin, Ricinus communis
      agglutinin (RCA(120)), were observed by the increase and decrease in absorbance
      at 550nm corresponding to localized surface plasmon resonance (LSPR) phenomena.
      The Cys-Lac SAM-carrying glass chip showed a strong non-specific adsorption of
      the lectin, whereas the DT-PLAMA brush-carrying one reversibly associated with
      the lectin, indicating reusability of the latter device. The apparent association
      constant of the lectin with the galactose residues in the DT-PLAMA brush was much
      larger than the association constant for free galactose, and the detection limit
      of RCA(120) by the glycopolymer brush-modified device was satisfactorily low.
      Furthermore, a microscopic observation clearly indicated that the DT-PLAMA brush
      could reversibly associate with a HepG2 cell having galactose receptors, though
      these processes could not be observed spectrophotometrically due to a gigantic
      size of the cell.

PMID- 18614342
TI  - Locally advanced non-metastatic pancreatic cancer--can we do more?

PMID- 18614343
TI  - Reversible lipidization of somatostatin analogues for the liver targeting.
AB  - Tyr(3)-octreotide (TOC), a somatostatin analogue, is reversibly lipidized for
      passive delivery to the liver with the aim of increasing its association with
      hepatocytes. The reversibly lipidized TOC (REAL-TOC) was formed by the
      conjugation of the N-palmitoyl cysteinyl moiety to the cysteinyl residues of
      reduced TOC through disulfide linkages and characterized by matrix-assisted laser
      desorption/ionization (MALDI)-time of flight (TOF) analysis. The measured mass of
      REAL-TOC (M+H)(+) is 1752.31 Da (calculated mass: 1752.78), confirming that two
      molecules of N-palmitoyl cysteines are linked to TOC via disulfide bonds. TOC and
      REAL-TOC were radioiodinated and administered to mice. Their biodistribution and
      intrahepatic distribution were subsequently investigated. The area under the
      curve (AUC) of (125)I-REAL-TOC in the liver was 3.8-fold greater than that of
      (125)I-TOC, with 20.5% and 5.8% of the injected dose (ID)/g of (125)I-REAL-TOC
      remaining in the liver at 2 and 24h post injection, respectively. Within the
      liver, TOC was primarily distributed to parenchymal cells (PC). Nevertheless, TOC
      was quickly excreted out and only 2.4% ID per 100mg protein remained in the PC at
      2h post injection. (125)I-REAL-TOC was retained in PC for up to 2h with a
      constant concentration of around 6% ID/100mg protein. (125)I-REAL-TOC was also
      highly associated with nonparenchymal cells (NPC) at significantly higher levels
      than (125)I-TOC at 10min, 1h and 2h post injection. Since somatostatin analogues
      have been evaluated for treating late-stage hepatocellular carcinoma (HCC), the
      reversibly lipidized conjugates may possess enhanced therapeutic efficacy due to
      the liver-targeting effect.

PMID- 18614344
TI  - Dietary fish oil associated with increased apoptosis and modulated expression of
      Bax and Bcl-2 during 7,12-dimethylbenz(alpha)anthracene-induced mammary
      carcinogenesis in rats.
AB  - The present study investigated the chemopreventive effect of dietary fish oil
      (Maxepa), rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on
      induction of apoptosis in mammary carcinogenesis model. Mammary carcinogenesis
      was initiated by a single, tail vein injection of 7,12
      dimethylbenz(alpha)anthracene (DMBA) (0.5mg/0.2ml corn oil/100g body weight) at 7
      weeks of animal age. Ninety female Sprague-Dawley rats were divided into two
      parts: part one was used for histology and immunohistochemical study and part two
      for morphological analysis. Each part consists of three experimental groups
      having 15 animals, i.e., Group A (DMBA control), Group B (DMBA+fish oil) and
      Group C (DMBA+corn oil). Rats were fed either fish oil or corn oil
      (0.5ml/day/rat) by oral gavage, 2 weeks prior to DMBA injection. Treatment was
      continued 25 weeks, studying histopathology, expression of Bax and Bcl-2 proteins
      by immunohistochemistry and apoptosis by TUNEL assay and morphological study at
      36 weeks. Results showed that the fish oil-treated group exhibited a substantial
      increase in Bax (p<0.05) immunolabelling and a reduction of Bcl-2
      immunopositivity (p<0.05), and increased TUNEL-positive apoptotic cells (p<0.05);
      however, corn oil treatment did not show these beneficial effects toward mammary
      preneoplasia. We conclude that fish oil has the potential to play a significant
      role in limiting mammary tumourigenesis in vivo.

PMID- 18614345
TI  - Clinical usefulness of fractional exhaled nitric oxide for diagnosing prolonged
      cough.
AB  - BACKGROUND: Prolonged cough is one of the troublesome symptoms commonly seen in
      daily practice. Especially, detection of allergic cough such as bronchial asthma
      (BA), cough variant asthma (CVA) and eosinophilic bronchitis without asthma (EB)
      is important because the prevalence of these disorders are high. We previously
      reported fractional exhaled nitric oxide (FeNO) can be a non-invasive marker of
      allergic airway inflammation. We examined whether FeNO could be applicable for
      the proper diagnosis of prolonged cough. METHOD: About 71 consecutive subjects
      complaining prolonged cough who gave informed consent for the study were
      enrolled. FeNO, pulmonary function tests, bronchial hyperresponsiveness (BHR),
      IgE, and eosinophils in induced sputum and peripheral blood were measured. Final
      diagnosis of the subjects was 30 with BA, 18 with CVA, 8 with EB, and 15 with
      other respiratory disorders (Others). RESULT: FeNO had significant correlations
      with non-specific IgE, mite-specific IgE, FEV/FVC, BHR, and eosinophils. The
      level of cedar-specific IgE was significantly higher in subjects with EB than
      CVA. FeNO levels in BA and CVA were significantly higher than those in EB and
      Others. The optimal cutoff level of FeNO was 38.8 ppb with sensitivity of 79.2%
      and specificity of 91.3% for distinguishing BA and CVA from EB and Others.
      CONCLUSION: FeNO could be used as a diagnostic marker of prolonged cough,
      especially for the differential diagnosis BA and CVA from EB and others.

PMID- 18614346
TI  - Clinico-pathologic study of pulmonary carcinoid tumours--a retrospective analysis
      and review of literature.
AB  - OBJECTIVE: To determine the characteristic clinico-pathologic features of
      pulmonary carcinoid tumours in India. METHODS: Retrospective analysis of the
      clinico-pathologic and radiologic data of patients with pulmonary carcinoid
      tumours from the department of Pulmonary Medicine of the Christian Medical
      College, a tertiary care teaching hospital in Southern India, over a study period
      of 3 years (2001-2004). RESULTS: There were 25 cases of pulmonary carcinoid
      tumours: typical 22 (88%) and atypical 3 (12%). The ratio of female to male was
      0.8:1. There were 3 smokers (all of whom were males) in the typical carcinoid
      group and none in the atypical carcinoid group. Haemoptysis and cough were the
      commonest presenting symptoms. The common radiologic findings were post
      obstructive pneumonitis or atelectasis, and mass lesion. Carcinoid syndrome was
      not present in any patient. Most of the tumours were central (n=23; 92%) and in
      the main bronchi (n=13; 52%). The most common site was the right main bronchus
      (n=9; 36%). Diagnosis was made by flexible bronchoscopy and bronchial biopsy in
      23 patients (92%). The tumour bled significantly following biopsy in most
      patients; however, there was no mortality, and only 1 patient required blood
      transfusion. Surgical option was offered to most; 13 patients (52%) had
      pneumonectomy and 4 patients (16%) had lobectomy. A review of large series from
      the literature is also presented. CONCLUSION: The clinico-pathologic and
      radiologic features of pulmonary carcinoid tumours are presented. We report the
      first series of pulmonary carcinoid tumours from India.

PMID- 18614347
TI  - Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50
      microg) on COPD exacerbations.
AB  - OBJECTIVES: COPD exacerbations are associated with significant morbidity and
      mortality. This randomized, double-blind, parallel-group, multicenter study
      evaluated the effect of fluticasone propionate/salmeterol 250/50 and salmeterol
      50 microg twice daily on moderate to severe exacerbations. METHODS: Patients
      received standardized treatment with fluticasone propionate/salmeterol 250/50
      during a 1-month run-in, followed by randomization to fluticasone
      propionate/salmeterol 250/50 or salmeterol for 12 months. Moderate to severe
      exacerbations were defined as worsening symptoms of COPD requiring treatment with
      oral corticosteroids, antibiotics, or hospitalization. RESULTS: In 782 patients
      with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with
      fluticasone propionate/salmeterol 250/50 significantly reduced (1) the annual
      rate of moderate to severe exacerbations by 30.5% compared with salmeterol (1.06
      and 1.53 per subject per year, respectively, p<0.001), (2) the risk of time to
      first exacerbation by 25% (hazard ratio=0.750, p=0.003) and (3) the annual rate
      of exacerbations requiring oral corticosteroids by 40% (p<0.001). Clinical
      improvements observed during run-in treatment with fluticasone
      propionate/salmeterol 250/50 were better maintained over 12 months with
      fluticasone propionate/salmeterol 250/50 than salmeterol. Adverse events were
      reported for a similar percentage of subjects across groups. A higher reporting
      of pneumonia was observed with fluticasone propionate/salmeterol 250/50 than
      salmeterol (7% vs. 4%). CONCLUSIONS: We conclude that fluticasone
      propionate/salmeterol 250/50 is more effective than salmeterol at reducing the
      rate of moderate to severe exacerbations over 1 year. The benefits of this
      reduction relative to the risk of a higher incidence of reported pneumonia should
      be considered. This study supports the use of fluticasone propionate/salmeterol
      250/50 for the reduction of COPD exacerbations in patients with COPD.

PMID- 18614348
TI  - Co-combustion of agricultural residues with coal in a fluidized bed combustor.
AB  - Power generation from biomass is an attractive technology that utilizes
      agricultural residual waste. In order to explain the behavior of biomass-fired
      fluidized bed incinerator, biomass sources from agricultural residues (rice husk
      and palm kernel) were co-fired with coal in a 0.15m diameter and 2.3m high
      fluidized bed combustor. The combustion efficiency and carbon monoxide emissions
      were studied and compared with those for pure coal combustion. Co-combustion of a
      mixture of biomass with coal in a fluidized bed combustor designed for coal
      combustion increased combustion efficiency up to 20% depending upon excess air
      levels. Observed carbon monoxide levels fluctuated between 200 and 900 ppm with
      the addition of coal. It is evident from this research that efficient co-firing
      of biomass with coal can be achieved with minimal modifications to existing coal
      fired boilers.

PMID- 18614349
TI  - Angiogenesis as a target in neuroblastoma.
AB  - Several research investigations on neuroblastoma (NB) have shown the important
      dependency of this embryonic tumour on angiogenesis, especially in the advanced
      and aggressive stages. However, the first pre-clinical data on anti-angiogenic
      drugs in NB have not been published until recently and clinical trials with anti
      angiogenic agents in NB treatment protocols are still missing. Here, we summarise
      current knowledge on the important role and mechanisms of angiogenesis in NB, and
      report available pre-clinical results of anti-angiogenic agents used to treat NB.
      This review clearly shows that angiogenesis is a target in NB and that clinical
      trials are urgently needed to bring forward promising anti-angiogenesis treatment
      strategies into NB therapy.

PMID- 18614350
TI  - Overexpression of CEACAM6 promotes migration and invasion of oestrogen-deprived
      breast cancer cells.
AB  - Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an
      intercellular adhesion molecule that is overexpressed in a wide variety of human
      cancers, including colon, breast and lung and is associated with tumourigenesis,
      tumour cell adhesion, invasion and metastasis. In this study, we showed that
      CEACAM6 was overexpressed in a panel of oestrogen receptor (ERalpha)-positive
      human breast cancer cell lines (MCF-7:5C and MCF-7:2A) that have acquired
      resistance to oestrogen deprivation, and this overexpression was associated with
      a more aggressive invasive phenotype in vitro. Expression array analysis revealed
      that MCF-7:5C and MCF-7:2A cells overexpressed CEACAM6 mRNA by 27-fold and 12
      fold, respectively, and were 6-15-times more invasive compared to non-invasive
      wild-type MCF-7 cells which expressed low levels of CEACAM6. Suppression of
      CEACAM6 expression using small interfering RNA (siRNA) completely reversed
      migration and invasion of MCF-7:5C and MCF-7:2A cells and it significantly
      reduced phosphorylated Akt and c-Src expression in these cells. In conclusion,
      our findings establish CEACAM6 as a unique mediator of migration and invasion of
      drug resistant oestrogen-deprived breast cancer cells and suggest that this
      protein could be an important biomarker of metastasis.

PMID- 18614351
TI  - Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence?
      What clinicians need to know.
AB  - Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking
      plant compounds called phytoestrogens can bind to oestrogen receptors and exert
      weak oestrogenic effects. Despite this activity, epidemiological studies suggest
      that the incidence of breast cancer is lower in countries where the intake of
      phytoestrogens is high, implying that these compounds may reduce breast cancer
      risk, and possibly have an impact on survival. Isoflavones and lignans are the
      most common phytoestrogens in the diet. In this article, we present findings from
      human observational and intervention studies related to both isoflavone and
      lignan exposure and breast cancer risk and survival. In addition, the clinical
      implications of these findings are examined in the light of a growing dietary
      supplement market. An increasing number of breast cancer patients seek to take
      supplements together with their standard treatment in the hope that these will
      either prevent recurrence or treat their menopausal symptoms. Observational
      studies suggest a protective effect of isoflavones on breast cancer risk and the
      case may be similar for increasing lignan consumption although evidence so far is
      inconsistent. In contrast, short-term intervention studies suggest a possible
      stimulatory effect on breast tissue raising concerns of possible adverse effects
      in breast cancer patients. However, owing to the dearth of human studies
      investigating effects on breast cancer recurrence and survival the role of
      phytoestrogens remains unclear. So far, not enough clear evidence exists on which
      to base guidelines for clinical use, although raising patient awareness of the
      uncertain effect of phytoestrogens is recommended.

PMID- 18614353
TI  - Growth kinetics of Chlorella vulgaris and its use as a cathodic half cell.
AB  - The kinetics of growth of the algal species Chlorella vulgaris has been
      investigated using CO(2) as the growth substrate. The growth rate was found to
      increase as the dissolved CO(2) increased to 150 mg/L, but fell dramatically at
      higher concentrations. Increasing the radiant flux also increased growth rate.
      With a radiant flux of 32.3 mW falling directly on the 500 mL culture media, the
      growth rate reached up to 3.6 mg of cells/L-h. Both pH variation (5.5-7.0) and
      mass transfer rate of CO(2) (K(L)a between 6h(-1) and 17 h(-1)) had little effect
      on growth rate. Growing on glucose, the yeast Saccharomyces cerevisiae produced a
      stable 160 mV potential difference when acting as a microbial fuel cell anode
      with ferricyanide reduction at the cathode. The algal culture was observed to be
      a workable electron acceptor in a cathodic half cell. Using an optimum methylene
      blue mediator concentration, a net potential difference of 70 mV could be
      achieved between the growing C. vulgaris culture acting as a cathode and a 0.02 M
      potassium ferrocyanide anodic half cell. Surge current and power levels of 1.0
      microA/mg of cell dry weight and 2.7 mW/m(2) of cathode surface area were
      measured between these two half cells.

PMID- 18614352
TI  - Impact of whole-body 18F-FDG PET on diagnostic and therapeutic management of
      Medical Oncology patients.
AB  - AIM: Most studies evaluating positron-emission tomography (PET) impact on
      decision making are based on questionnaires sent to referring physicians, with
      low response rates and potential bias. Studies directly evaluating influence of
      PET on routine management of Medical Oncology patients are scarce. PATIENTS AND
      METHODS: We retrospectively studied all patients evaluated by whole-body (18)F
      FDG PET during 1 year in a Haematology/Oncology Department. We collected
      information regarding indication, PET results, modification of diagnostic and
      therapeutic management and adequacy of therapeutic changes. RESULTS: One hundred
      consecutive patients having PET were evaluated. Diagnostic strategy was modified
      in 63% of patients (30% avoiding biopsy). Therapeutic management was modified by
      PET in 34% of cases: changes were classified as adequate in 30% and as inadequate
      in 4% of patients. CONCLUSIONS: Our study shows a major impact of PET in the
      diagnostic and therapeutic management of cancer patients and supports its
      introduction as a routine diagnostic tool in Medical Oncology.

PMID- 18614354
TI  - A site-specific slurry application technique on grassland and on arable crops.
AB  - There is evidence that unequal slurry application on agricultural land
      contributes to N losses to the environment. Heterogeneity within fields demands
      adequate response by means of variable rate application. A technique is presented
      which allows site-specific application of slurry on grassland and arable land
      based on pre-defined application maps. The system contains a valve controlling
      flow rate by an on-board PC. During operation, flow rate is measured and scaled
      against set point values given in the application map together with the
      geographic position of the site. The systems worked sufficiently precise at a
      flow rate between 0 and 25 l s(-1) and an offset of actual slurry flow from set
      point values between 0.33 and 0.67 l s(-1). Long-term experimentation is required
      to test if site-specific application de facto reduces N surplus within fields and
      so significantly contributes to the unloading of N in agricultural areas.

PMID- 18614355
TI  - Continuous thorium biosorption--dynamic study for critical bed depth
      determination in a fixed-bed reactor.
AB  - The objective of the work was to evaluate the biosorption of thorium by the
      seaweed Sargassum filipendula in a dynamic system. Different bed depths were
      tested with the purpose of evaluating the critical bed depth for total uptake of
      the radioactive element. Several bed depths were tested, ranging from 5.0 to 40.0
      cm. Bed depths tested presented distinct capacities to accumulate thorium. An
      increase in biosorption efficiency was observed with an increase in bed depth.
      The 30.0 cm bed produced an effluent still containing detectable levels of
      thorium. The critical bed depth suitable for a complete removal of thorium by
      S.filipendula biomass was equal to 40.0 cm.

PMID- 18614356
TI  - Proteolytic activity in stored aerobic granular sludge and structural integrity.
AB  - Aerobic granules lose stability during storage. The goal of this work was to
      highlight the main cause of stability loss for stored granules as intracellular
      protein hydrolysis. The quantity of extracellular proteins was noted to be
      significantly lower during granule storage, and protease enzyme activities were
      correspondingly higher in the cores of stored granules. The proteolytic bacteria,
      which secrete highly active protease enzymes, were for the first time isolated
      and characterized by analyzing 16S rDNA sequences. The proteolytic bacteria
      belonged to the genera Pseudomonas, Raoultella, Acinetobacter, Pandoraea,
      Klebsiella, Bacillus and uncultured bacterium, and were grouped into
      Proteobacteria, Enterobacteria and Firmicutes. The PB1 (Pseudomonas aeruginosa)
      strain, which exhibited very high proteolytic activity during the skim milk agar
      test, was located at the core regime with active protease enzymes, and was close
      to the obligate anaerobic strain Bacteroides sp. Hence, the extracellular
      proteins in stored granules were proposed to be hydrolyzed by enzymes secreted by
      proteolytic bacteria with the hydrolyzed products ultimately being used by nearby
      anaerobic strains. This process gradually digests the protein core, and
      eventually consumes the entire granule.

PMID- 18614357
TI  - The effect of glycerol as a sole and secondary substrate on the growth and fatty
      acid composition of Rhodotorula glutinis.
AB  - Rhodotorula glutinis is a yeast that produces copious quantities of lipids in the
      form of triacylglycerols (TAG) and can be used to make biodiesel via a
      transesterification process. The ester bonds in the TAG are broken leaving behind
      two products: fatty acid methyl esters and glycerol that could provide an
      inexpensive carbon source to grow oleaginous yeast R. glutinis. Described here
      are the effects of different growth substrates on TAG accumulation and fatty
      acids produced by R. glutinis. Yeast cultured 24h on medium containing dextrose,
      xylose, glycerol, dextrose and xylose, xylose and glycerol, or dextrose and
      glycerol accumulated 16, 12, 25, 10, 21, and 34% TAG on a dry weight basis,
      respectively. Lipids were extracted from R. glutinis culture and transesterified
      to form fatty acid methyl esters. The results show a difference in the degree of
      saturation for the carbon sources tested. Cells cultivated on glycerol alone had
      the highest degree of unsaturated fatty acids at 53% while xylose had the lowest
      at 25%. R. glutinis can be cultivated on all sugars tested as single carbon
      substrates or in mixtures. Glycerol may be used as secondary or primary carbon
      substrate.

PMID- 18614358
TI  - Flow injection analysis-based methodology for automatic on-line monitoring and
      quality control for biodiesel production.
AB  - An automated on-line approach based on determination of free and bound glycerol
      was here proposed to monitor biodiesel production. The method was based on liquid
      liquid extraction of glycerol from the biodiesel to an aqueous ethanolic phase in
      which glycerol is oxidized to formaldehyde with meta periodate with subsequent
      reaction with acetylacetone. The reaction product was photometrically measured at
      410 nm. Free and bound glycerol were differentiated by glycerides hydrolysis with
      potassium ethylate. The experimental set-up consisted of a flow-injection
      manifold for liquid-liquid extraction without phase separation and iterative
      change of the flow direction that enabled: (a) filling the flow manifold with a
      meta periodate-acetylacetone acceptor phase; (b) sampling of small amounts
      (microl) from the reactor; (c) determination of free glycerol by extraction from
      biodiesel to the aqueous phase with simultaneous oxidation-reaction with
      acetylacetone in the acceptor phase; (d) continuous monitoring of the aqueous
      phase by passage through a photometric detector; (e) filling the flow manifold
      with a potassium ethylate-meta periodate-acetylacetone new acceptor phase; (d)
      repetition of steps b-to-d to determine total glycerol after saponification of
      the bound glycerol by potassium ethylate; and (f) determination of bound glycerol
      by difference between the second and first analyses. The results showed that the
      proposed automated on-line method is a suitable option in routine analysis during
      biodiesel production.

PMID- 18614359
TI  - A conceptual comparison of bioenergy options for using mountain pine beetle
      infested wood in Western Canada.
AB  - Biomass is nearly carbon neutral and can be used for the production of various
      liquid fuels and chemicals. Decisions on biomass utilization should be based on
      the most economical and mature route. This study analyzes mountain pine beetle
      (MPB) killed wood as the feedstock for production of bio-ethanol and bio-oil and
      compares it with the direct combustion route to produce electricity. The MPB
      infestation of British Columbia's (BC), a western province of Canada, forest has
      reached an epidemic proportion and is spread over an area of 10 millionha.
      According to the current estimates of BC's Ministry of Forests and Range, about 1
      billion m(3) of trees would be killed by MPB by 2013. This infestation would
      result in large scale loss of jobs and the standing dead trees are a fire hazard
      and if left unharvested will decay and release carbon back to the atmosphere. The
      cost of bio-ethanol production from a 2100dry tonne/day plant using the infested
      wood for two locations (one remote and other near the industry) in BC is in the
      range of C$0.37-C$0.40/l (C$1.40-C$1.51/gallon). Similarly, cost of bio-oil
      production from a 220dry tonne/day plant using the infested wood for same two
      locations in BC is in the range of C$0.27-C$0.29/l (C$1.02-C$1.09/gallon). The
      cost of producing electricity using this bio-oil is above C$100/MWh which is
      higher than the current power price in BC. This cost is also higher than the cost
      of production of electricity by direct combustion of infested wood in a boiler
      (C$68-C$74/MWh).

PMID- 18614360
TI  - Accurate quantitative determination of monoaromatic compounds for the monitoring
      of bioremediation processes.
AB  - This work demonstrated that the protocol for sample treatment, necessary to
      remove the microbial biomass prior to an analysis, is a critical issue for
      obtaining accurate results when volatile compounds are present. Two phenomena
      were observed, solute adsorption and stripping in the gas phase in contact with
      the liquid. It was demonstrated that the best protocol involved centrifugation
      using poly tetra fluoro ethylene (PTFE) capped tubes completely filled with the
      liquid suspension, i.e. without any gas phase inside it. This approach allowed a
      solute loss lower than 1%. The results also indicated that the optimum
      centrifugation conditions were 10000g at 10 degrees C for 10 min. Alternatively,
      it was found that the centrifugation technique developed could be used for the
      experimental determination of the activity coefficient of solubilized volatile
      compounds. This study additionally highlighted the fact that polyvinylidene
      fluoride micro filters (PVDF) and propylene GH polypro membranes (GHP) with a
      pore size of 0.45 microm could be used for biomass separation, although 10-12%
      monoaromatic adsorption by membrane was still present. In addition, a simple and
      sensitive method using high performance liquid chromatography (HPLC) with a UV
      detector set at the optimum point of 208 nm was developed for assessing the
      concentrations of BTX in samples taken from bioremediation processes. Minimum
      detection limits of 5, 4 and 10 microg L(-1) were obtained for benzene, toluene
      and mixed xylenes, respectively.

PMID- 18614361
TI  - Antimutagenic and antioxidant activities of quebracho phenolics (Schinopsis
      balansae) recovered from tannery wastewaters.
AB  - Quebracho extracts are used in tannery due to their high concentration of
      phenolics. The Mexican tannery industry uses around 450 kg/m(3) of which, 150
      kg/m(3) remains in wastewaters and are discharged in drain pipe systems or
      rivers. The quebracho phenolics recovered from tannery wastewater (QPTW) was
      characterized by HPLC. The antimutagenic and antioxidant activities as well as
      the microbiological quality were evaluated. Total phenolic content of QPTW was
      621mg catechin equivalent/g sample. Gallic and protocatechuic acids were the
      major components characterized by HPLC. QPTW showed an inhibition range on
      aflatoxin B(1) mutagenicity from 16 to 60% and was dose-dependent. Antioxidant
      activity (defined as beta-carotene bleaching) of QPTW (64.4%) at a dose of
      12.3mg/mL was similar to that of BHT (68.7%) at a dose of 0.33 mg/mL, but lower
      than Trolox (90.8% at a dose of 2.5mg/mL); meanwhile antiradical activity
      (measured as reduction of DPPH) (60.8%) was higher than that of BHT (50.8%) and
      Trolox (34.2%). Quebracho residues were demonstrated to be an outstanding source
      of phenolic acids and for research and industrial uses.

PMID- 18614362
TI  - Application of three methods used for the evaluation of polycyclic aromatic
      hydrocarbons (PAHs) bioaccessibility for sewage sludge composting.
AB  - Three chemical approaches were compared to assess the bioaccessibility of PAHs
      during four sewage sludge composting. In the present study solid phase extraction
      with Tenax-TA and two non-exhaustive/mild-solvent extraction techniques with n
      butanol (BtOH) and hydroxypropyl[beta]cyclodextrin (HPCD) have been applied. The
      content of the PAHs sum in individual sludges ranged from 2.83 to 9.95 mg/kg.
      Mainly 4-ring PAHs predominated in all sludges. The content of the bioaccessible
      fraction of PAHs determined using the BtOH and HPCD methods was usually twice
      higher than with the use of Tenax-TA adsorbent. The share of the bioaccessible
      fraction depended on the method applied and sewage sludge type. In the case of
      the PAH sums it ranged from 28.1% to 54.5% (Tenax-TA), from 25.7% to 80.9% (BtOH)
      and from 60.2% to 83.5% (HPCD). As a result of composting, the share of the
      bioaccessible fraction decreased by about 50% in most of the sludges examined.
      The reliable prediction of individual PAHs losses was observed for many of the
      PAHs; however, for a number of them, this was confirmed in more than two of the
      sludges examined.

PMID- 18614363
TI  - Adsorptive removal of copper and nickel ions from water using chitosan coated PVC
      beads.
AB  - A new biosorbent was developed by coating chitosan, a naturally and abundantly
      available biopolymer, on to polyvinyl chloride (PVC) beads. The biosorbent was
      characterized by FTIR spectra, porosity and surface area analyses. Equilibrium
      and column flow adsorption characteristics of copper(II) and nickel(II) ions on
      the biosorbent were studied. The effect of pH, agitation time, concentration of
      adsorbate and amount of adsorbent on the extent of adsorption was investigated.
      The experimental data were fitted to Langmuir and Freundlich adsorption
      isotherms. The data were analyzed on the basis of Lagergren pseudo first order,
      pseudo-second order and Weber-Morris intraparticle diffusion models. The maximum
      monolayer adsorption capacity of chitosan coated PVC sorbent as obtained from
      Langmuir adsorption isotherm was found to be 87.9 mg g(-1) for Cu(II) and 120.5
      mg g(-1) for Ni(II) ions, respectively. In addition, breakthrough curves were
      obtained from column flow experiments. The experimental results demonstrated that
      chitosan coated PVC beads could be used for the removal of Cu(II) and Ni(II) ions
      from aqueous medium through adsorption.

PMID- 18614364
TI  - Discovery of imidazole carboxamides as potent and selective CCK1R agonists.
AB  - High-throughput screening revealed diaryl pyrazole 3 as a selective albeit modest
      cholecystokinin 1 receptor (CCK1R) agonist. SAR studies led to the discovery and
      optimization of a novel class of 1,2-diaryl imidazole carboxamides. Compound 44,
      which was profiled extensively, showed good in vivo mouse gallbladder emptying
      (mGBE) and lean mouse overnight food intake (ONFI) reduction activities.

PMID- 18614365
TI  - Successful kinase bypass with new acyclovir phosphoramidate prodrugs.
AB  - Novel phosphoramidates of acyclovir have been prepared and evaluated in vitro
      against acyclovir-sensitive and -resistant herpes simplex virus (HSV) types 1 and
      2 and varicella-zoster virus (VZV). Unlike the parent nucleoside these novel
      phosphate prodrugs retain antiviral potency versus the ACV-resistant virus
      strain, suggesting an efficient bypass of the viral thymidine kinase.

PMID- 18614366
TI  - Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo
      activity.
AB  - The biphenyl amides (BPAs) are a novel series of p38alpha MAP kinase inhibitor.
      The optimisation of the series to give compounds that are potent in an in vivo
      disease model is discussed. SAR is presented and rationalised with reference to
      the crystallographic binding mode.

PMID- 18614367
TI  - Exploring 9-benzyl purines as inhibitors of glutamate racemase (MurI) in Gram
      positive bacteria.
AB  - An early SAR study of a screening hit series has generated a series of 9-benzyl
      purines as inhibitors of bacterial glutamate racemase (MurI) with micromolar
      enzyme potency and improved physical properties. X-ray co-crystal EI structures
      were obtained.

PMID- 18614368
TI  - Role of myeloid cells in tumor angiogenesis and growth.
AB  - Cells of the innate immune system have a key role in maintaining homeostasis by
      providing the first line of defense against many pathogens. Innate immunity can
      also modulate the activity of acquired immunity by several mechanisms. However,
      subsets of myeloid cells can facilitate tumor growth, because these cells produce
      angiogenic factors and can also prevent the immune system from attacking tumor
      cells. Recent studies also emphasize the role of myeloid cells in mediating
      refractoriness to anti-VEGF treatments. This function of myeloid cells occurs
      through a proangiogenic pathway that is, at least in part, driven by the secreted
      protein Bv8. This review summarizes recent findings on the complex role of bone
      marrow-derived cells in tumor growth.

PMID- 18614369
TI  - Rib-head osteotomies for posterior placement of expandable cages in the treatment
      of metastatic thoracic spine tumors.
AB  - Metastatic spine tumors commonly affect the thoracic spine, and effective tumor
      control often requires corpectomy with reconstruction. In some instances,
      anterior approaches for corpectomy may be difficult or less than ideal because of
      medical co-morbidities, pulmonary disease or difficult access behind the
      mediastinum. Thus, posterior approaches are commonly used for corpectomies with
      anterior column reconstruction in the thoracic spine. Expandable cages have the
      advantage of restoring height, correcting kyphosis, and providing secure wedging
      between the vertebral bodies. However, the spinal cord and thorax may prevent
      direct, easy access for placement of expandable cages. Reconstruction has been
      performed with different materials; however, expandable cages have hitherto been
      less frequently used because of their size and difficulty expanding the cages
      posteriorly. We describe a technical note that may facilitate the placement of an
      expandable cage in the thoracic spine after posterior transpedicular
      corpectomies.

PMID- 18614370
TI  - Cerebral phaeohyphomycosis mimics high-grade astrocytoma.
AB  - The incidence of cerebral phaeohyphomycosis, an infection caused by a dark
      pigmented fungus, is increasing. The infection may mimic a high-grade glioma
      clinically and radiographically. Magnetic resonance spectroscopy may be helpful
      in differentiating the two. We report two cases to increase the awareness of
      cerebral phaeohyphomycosis in the clinical neurosciences. Early biopsy
      establishing the diagnosis, followed by aggressive combined surgical and medical
      management is necessary for a good outcome.

PMID- 18614371
TI  - Intravascular lymphoma presenting as progressive paraparesis.
AB  - We present a patient with subacute progressive paraparesis secondary to
      intravascular lymphoma restricted to the spinal cord where initial laboratory and
      imaging studies were inconclusive. We emphasise the importance of a systematic
      approach to the diagnosis and highlight the utility of spinal cord biopsy to
      establish the definitive diagnosis of this rare but treatable illness.

PMID- 18614372
TI  - HRTEM and TEM studies of amorphous structures in ZrNiTiCu base alloys obtained by
      rapid solidification or ball milling.
AB  - Amorphous structure of Ti(25)Zr(17)Ni(29)Cu(29) composition was studied. Alloys
      were prepared either by rapid solidification using melt spinning or by high
      energy ball milling. The composition of multi-component eutectic in slowly cooled
      samples of ZrNiTiCu alloy was determined using EDS measurements in scanning
      microscope of slowly cooled cast samples. The alloys of eutectic composition were
      melt-spun or ball-milled. Transmission electron microscopy (TEM) studies of melt
      spun ribbons from alloys near eutectic composition did not show presence of
      nanocrystals within the amorphous structure. TEM studies of ball-milled powders
      showed presence of nanocrystallites of size 2-5 nm. The electron diffraction
      pattern showed intense diffused ring due to the presence of the amorphous phase
      and a weak spot due to crystalline phases which were difficult to identify. The
      high temperature high-pressure compaction in vacuum of amorphous ball-milled
      powders resulted in a similar structure like in the powders showing nanocrystals
      embedded in the amorphous matrix. The crystallites were imaged using HREM.
      Interplanar distances were measured in pictures obtained by inverse fast Fourier
      transform (IFFT) of atomic planes to obtain better contrast. Analysis of the IFFT
      from high-resolution micrographs allowed to identify Cu(10)Zr(7) phase. Point
      analysis and elemental mapping performed using nondispersive X-ray energy
      spectroscopy showed uniform elements distribution indicating that chemical
      segregation to nanocrystals is within measurement error.

PMID- 18614373
TI  - Polyamine metabolism in maize tumors induced by Ustilago maydis.
AB  - Alterations occurring in polyamine metabolism of maize in tumors formed during
      the interaction with the biotrophic pathogenic fungus Ustilago maydis were
      analyzed. During the process, a striking increase in maize polyamine
      biosynthesis, mainly free and conjugated putrescine occurred in the tumors
      induced by the fungus, and in the neighbor plant tissues. This increase
      correlated with an activation mainly of Adc, Samdc1, Zmsamdc2 and Zmsamdc3, but
      not of Zmodc, Zmspds1 and Zmspds2 genes, and an elevation in arginine
      decarboxylase activity, confirming a predominant role of this enzyme in the
      process. Evidences for a possible contribution of spermidine and spermine
      degradation by polyamine oxidase activity, probably related to cell wall
      stiffening or lignification during tumor growth, were also obtained. It is
      suggested that polyamines, mainly putrescine, might play an active role in the
      pathosystem maize-U. maydis.

PMID- 18614374
TI  - An oxidative and salinity stress induced peroxisomal ascorbate peroxidase from
      Avicennia marina: molecular and functional characterization.
AB  - APX (EC, 1.11.1.11) has a key role in scavenging ROS and in protecting cells
      against their toxic effects in algae and higher plants. A cDNA encoding a
      peroxisomal ascorbate peroxidase, Am-pAPX1, was isolated from salt stressed
      leaves of Avicennia marina (Forsk.) Vierh. by EST library screening and its
      expression in the context of various environmental stresses was investigated. Am
      pAPX1 contains an ORF of 286 amino acids coding for a 31.4 kDa protein. The C
      terminal region of the Am-pAPX1 ORF has a putative transmembrane domain and a
      peroxisomal targeting signal (RKKMK), suggesting peroxisomal localization. The
      peroxisomal localization of Am-pAPX1 was confirmed by stable transformation of
      the GFP-(Ala)(10)-Am-pAPX1 fusion in tobacco. RNA blot analysis revealed that Am
      pAPX1 is expressed in response to salinity (NaCl) and oxidative stress (high
      intensity light, hydrogen peroxide application and excess iron). The isolated
      genomic clone of Am-pAPX1 was found to contain nine exons. A fragment of 1616bp
      corresponding to the 5' upstream region of Am-pAPX1 was isolated by TAIL-PCR. In
      silico analysis of this sequence reveals the presence of putative light and
      abiotic stress regulatory elements.

PMID- 18614375
TI  - Review of gene-expression profiling and its clinical use in breast cancer.
AB  - Despite advances in the treatment of early-stage breast cancer, physicians still
      lack the ability to accurately predict which individual patients will relapse and
      would benefit from adjuvant chemotherapy. Traditional clinicopathologic factors
      are important in helping to determine risk of relapse, but do not fully account
      for the biologic complexity of breast cancer. Gene-expression profiling has
      provided us with insight into the heterogeneity of breast cancer and led to the
      development of prognostic and predictive molecular gene signature models designed
      to aid in clinical decision-making. However, it remains to be determined how much
      refinement in prognosis genomic models provide over standard clinicopathologic
      features and whether these refinements translate into improvements in clinical
      practice. On-going large prospective multi-center clinical trials will provide us
      with information regarding the clinical utility of two of these assays, but for
      now, implementation of these models into widespread clinical practice remains
      limited.

PMID- 18614376
TI  - Development and validation of an ATP method for rapid estimation of viable units
      in lyophilised BCG Danish 1331 vaccine.
AB  - An assay for quantifying viability in BCG vaccine by determining intracellular
      ATP content was developed and validated. ATP content was determined by measuring
      bioluminescence in the presence of luciferin/luciferase. During development and
      validation the ATP method was compared to the conventional viable count method. A
      key step to obtain correlation between ATP content and CFU was found to be a
      period of pre-incubation in a growth medium before ATP determination. During the
      validation, the robustness, linearity, accuracy, precision, and range were
      studied. The method validation study showed that the method applied was robust
      and applicable to determine ATP content in lyophilised BCG for estimating
      viability in the BCG samples. By comparison with a conventional viable count
      method, a high correlation between ATP content and the viable count was found;
      this relationship can be applied in routine quality control to estimate viable
      count from the ATP content determined in a sample.

PMID- 18614377
TI  - What transmission electron microscopes can visualize now and in the future.
AB  - Our review concentrates on the progress made in high-resolution transmission
      electron microscopy (TEM) in the past decade. This includes significant
      improvements in sample preparation by quick-freezing aimed at preserving the
      specimen in a close-to-native state in the high vacuum of the microscope.
      Following advances in cold stage and TEM vacuum technology systems, the
      observation of native, frozen hydrated specimens has become a widely used
      approach. It fostered the development of computer guided, fully automated low
      dose data acquisition systems allowing matched pairs of images and diffraction
      patterns to be recorded for electron crystallography, and the collection of
      entire tilt-series for electron tomography. To achieve optimal information
      transfer to atomic resolution, field emission electron guns combined with
      acceleration voltages of 200-300 kV are now routinely used. The outcome of these
      advances is illustrated by the atomic structure of mammalian aquaporin-O and by
      the pore-forming bacterial cytotoxin ClyA resolved to 12 A. Further, the Yersinia
      injectisome needle, a bacterial pseudopilus and the binding of phalloidin to
      muscle actin filaments were chosen to document the advantage of the high contrast
      offered by dedicated scanning transmission electron microscopy (STEM) and/or the
      STEM's ability to measure the mass of protein complexes and directly link this to
      their shape. Continued progress emerging from leading research laboratories and
      microscope manufacturers will eventually enable us to determine the proteome of a
      single cell by electron tomography, and to more routinely solve the atomic
      structure of membrane proteins by electron crystallography.

PMID- 18614378
TI  - Sharpening high resolution information in single particle electron
      cryomicroscopy.
AB  - Advances in single particle electron cryomicroscopy have made possible to
      elucidate routinely the structure of biological specimens at subnanometer
      resolution. At this resolution, secondary structure elements are discernable by
      their signature. However, identification and interpretation of high resolution
      structural features are hindered by the contrast loss caused by experimental and
      computational factors. This contrast loss is traditionally modeled by a Gaussian
      decay of structure factors with a temperature factor, or B-factor. Standard
      restoration procedures usually sharpen the experimental maps either by applying a
      Gaussian function with an inverse ad hoc B-factor, or according to the amplitude
      decay of a reference structure. EM-BFACTOR is a program that has been designed to
      widely facilitate the use of the novel method for objective B-factor
      determination and contrast restoration introduced by Rosenthal and Henderson
      [Rosenthal, P.B., Henderson, R., 2003. Optimal determination of particle
      orientation, absolute hand, and contrast loss in single-particle electron
      cryomicroscopy. J. Mol. Biol. 333, 721-745]. The program has been developed to
      interact with the most common packages for single particle electron
      cryomicroscopy. This sharpening method has been further investigated via EM
      BFACTOR, concluding that it helps to unravel the high resolution molecular
      features concealed in experimental density maps, thereby making them better
      suited for interpretation. Therefore, the method may facilitate the analysis of
      experimental data in high resolution single particle electron cryomicroscopy.

PMID- 18614379
TI  - The effect of short-term changes in body mass distribution on feed-forward
      postural control.
AB  - It was recently shown that short-term changes in the whole body mass and
      associated changes in the vertical position of the center of mass (COM) modify
      anticipatory postural adjustments (APAs) [Li X, Aruin AS. The effect of short
      term changes in the body mass on anticipatory postural adjustments. Exp Brain Res
      2007;181:333-46]. In this study, we investigated whether changes in the body mass
      distribution and related changes in the anterior-posterior COM position affect
      APA generation. Fourteen subjects were instructed to catch a 2.2 kg load with
      their arms extended while standing with no additional weight or while carrying a
      9.08 kg weight. Adding weight to a backpack, front pack or belly pocket was
      associated with an increase of the whole body mass, but it also involved changes
      in the anterior-posterior (A/P) and vertical positions of the COM.
      Electromyographic activity of leg and trunk muscles, body kinematics, and ground
      reaction forces were recorded and quantified within the typical time intervals of
      APAs. APAs were modified in conditions with changed body mass distribution:
      increased magnitude of anticipatory EMG activity in leg and trunk muscles, as
      well as co-activation of leg muscles and decreased anticipatory displacement of
      the COM in the vertical direction, were seen in conditions with increased body
      mass. Changes in the COM position induced in both A/P and vertical directions
      were associated with increased anticipatory EMG activity. In addition, they were
      linked to a co-activation of muscles at the ankle joints and significant changes
      in the center of pressure (COP) position. Modifications of the COM position
      induced in the A/P direction were related to increased anticipatory EMG activity
      in the leg and trunk muscles. At the same time, no significant differences in
      anticipatory EMG activity or displacement of COP were observed when changes of
      COM position were induced in the vertical direction. The study outcome suggests
      that the CNS uses different strategies while generating APAs in conditions with
      changes in the COM position induced in the anterior-posterior and vertical
      directions.

PMID- 18614380
TI  - Pernicious anemia in a patient with Type 1 diabetes mellitus and alopecia areata
      universalis.
AB  - A 27-year-old male, who had developed diabetes mellitus type 1 (DMT1) since the
      age of eighteen and alopecia areata universalis nine months later, attended the
      outpatient clinics complaining of general fatigue and shortness of breath. A
      Schilling test was indicative of pernicious anemia. Antigastric parietal cell
      (AGPA) and anti-intrinsic factor antibodies were positive, confirming diagnosis
      of pernicious anemia. Thyroid and Addison's disease were excluded. Gastroscopy
      revealed atrophic gastritis without any evidence of carcinoid tumors. The aim of
      this case, which, to our knowledge, is the first one to describe a correlation
      between diabetes mellitus Type 1 (DMT1), pernicious anaemia, and alopecia areata
      universalis, is to remind the clinician of the increased risk of pernicious
      anaemia and gastric carcinoids in DMT1 patients. Screening for AGPA followed by
      serum gastrin and vitamin B(12) levels constitute the most evidence-based
      diagnostic approach.

PMID- 18614381
TI  - Comparison of MR-arthrography and CT-arthrography in hyaline cartilage-thickness
      measurement in radiographically normal cadaver hips with anatomy as gold
      standard.
AB  - OBJECTIVE: To compare magnetic resonance (MR)-arthrography and multidetector
      spiral-computed-tomography (MDSCT)-arthrography in cartilage-thickness
      measurement, in hips without cartilage loss, with coronal anatomic slices as gold
      standard. METHOD: Institutional review board permission to study cadavers of
      individuals who willed their bodies to science was obtained. Two independent
      observers measured femoral and acetabular cartilage thicknesses of 12
      radiographically normal hips (six women, five men; age range, 52-98 years; mean
      age, 76.5 years), on MDSCT-arthrographic and MR-arthrographic reformations, and
      on coronal anatomic slices, excluding regions of cartilage loss. Inter- and
      intraobserver reproducibilities were determined. Analysis of variance (ANOVA) was
      used to test differences between MR-arthrographic and MDSCT-arthrographic
      measurement errors compared to anatomy. RESULTS: By MR-arthrography, cartilage
      was not measurable at approximately 50% of points on sagittal and transverse
      sections, compared to 0-6% of the points by MDSCT-arthrography. In the coronal
      plane, the difference between MDSCT-arthrographic and MR-arthrographic
      measurement errors was not significant (P=0.93). CONCLUSION: In the coronal
      plane, MR-arthrography and MDSCT-arthrography were similarly accurate for
      measuring hip cartilage thickness.

PMID- 18614383
TI  - Reversible disconnection of the hippocampal-prelimbic cortical circuit impairs
      spatial learning but not passive avoidance learning in rats.
AB  - Wistar rats, treated with the GABA(A) receptor agonist muscimol, were used to
      investigate the role of the hippocampal-prelimbic cortical (Hip-PLC) circuit in
      spatial learning in the Morris water maze task, and in passive avoidance learning
      in the step-through task. In the water maze task, animals were trained for three
      consecutive days and tested 24 h after the end of training. In the step-through
      task, the animals were trained once and tested 24h after training. On the
      training days, daily infusion of muscimol (0.5 microg/0.25 microl) was given (1)
      bilaterally to the ventral hippocampus (vHip), (2) bilaterally to the prelimbic
      cortex (PLC), (3) to the unilateral vHip and the ipsilateral PLC, or (4) for
      disconnecting the Hip-PLC circuit, to both the unilateral vHip and the
      contralateral PLC 30 min before training. The results showed that inhibition of
      the vHip resulted in disruption of performance in both tasks. Inhibition of the
      PLC produced impaired water maze performance, but had no effect on the step
      through task. Disconnection of the Hip-PLC circuit produced similar effects to
      PLC inhibition. However, simultaneous inhibition of the unilateral vHip and the
      ipsilateral PLC had little effect on performance of the water maze task. The
      results suggested that spatial learning depends on the Hip-PLC circuit, whereas
      passive avoidance learning is independent of this circuit.

PMID- 18614384
TI  - A role for yeast glutaredoxin genes in selenite-mediated oxidative stress.
AB  - Since the double Deltagrx1Deltagrx2 mutant is hypersensitive to selenite we
      decided to evaluate mechanisms underlying this phenomenon and establish the roles
      of other components of yeast glutaredoxin system, in particular glutaredoxin 5 in
      the selenite resistance. We found elevation in the intracellular and
      mitochondrial superoxide production in the Deltagrx1Deltagrx2 and Deltagrx5
      mutants after Se(IV) treatment. The last effect was more pronounced for cells
      lacking the mitochondrial Grx5 protein. We also recorded selenite-induced
      increase in the peroxide production in all strains tested. Nonfermentable carbon
      sources, glycerol and ethanol, augmented selenite toxicity. Hypo- and anoxia
      protected against the harmful effects of Se(VI). Augmentation of the
      intracellular levels of two endogenous antioxidants, erythroascorbic acid and
      glutathione confers resistance to selenite. We recorded a strain-unspecific,
      selenite-mediated decrease in the level of acid-soluble thiols. Collectively, our
      data demonstrate that hypersensitivity to the Deltagrx1Deltagrx2 and Deltagrx5
      disruptants to selenite is mediated by altered intracellular redox equilibrium.

PMID- 18614385
TI  - Parametric characterization of spinal motions in osteoporotic vertebral fracture
      at level T12 with fluoroscopy.
AB  - Vertebral fractures due to osteoporosis are a common skeletal disorder affecting
      the mobility of the patients, although little is known about the relationship
      between spinal kinematics and osteoporotic fracture. The purpose of this study
      was to characterize the motions of the thoracolumbar spine affected by
      osteoporotic vertebral fracture at level T12 and compare the results with those
      of non-fracture osteoporosis subjects. We examined the continuous segmental
      kinematics of the vertebrae, and describe the segmental motion of the spine when
      a fracture at T12 is present. Fluoroscopy sequences of the thoracolumbar spines
      during sagittal and lateral flexion were collected from 16 subjects with
      osteoporosis of their spine (6 with vertebral fractures at T12, 10 without a
      fracture). Vertebrae T10-L2 in each frame of the sequences were landmarked.
      Kinematic parameters were calculated based on the landmarks and motion graphs
      were constructed. Compared to the control subjects who did not have a fracture,
      fracture subjects had a more asymmetric lateral range of motion (RoM) and
      required a longer time to complete certain phases of the motion cycle which are
      parameterized as lateral flexion ratio and percentage of motion cycle,
      respectively. Prolonged deflection was more frequently found from the fracture
      group. Characterizing the motions of the fractured vertebra together with its
      neighboring vertebrae with these kinematic parameters is useful in quantifying
      the dysfunction and may be a valuable aid to tracking progress of treatment.

PMID- 18614386
TI  - Rheological properties of the tissues of the central nervous system: a review.
AB  - Knowledge of the biomechanical properties of central nervous system (CNS) tissues
      is important for understanding mechanisms and thresholds for injury, and aiding
      development of computer or surrogate models of these tissues. Many investigations
      have been conducted to estimate the properties of CNS tissues including under
      shear, compressive and tensile loading, however there is much variability in this
      body of literature, making it difficult to separate the material properties from
      effects that result from a given experimental protocol. This review summarises
      previous studies of brain and spinal cord properties; discussing their main
      findings and points of difference, and displays the reported data on comparable
      scales. Additionally, based on the observed effects of methodological choices on
      reported tissue properties, recommendations for future studies of brain and
      spinal cord properties are made.

PMID- 18614387
TI  - Down on main street: drugs and the small-town vortex.
AB  - Ethnographic research on social networks-especially that which focuses on rural
      or small-town drug use-is relatively rare. Drawing on qualitative interviews and
      focus groups conducted with illicit drug users residing in three counties in west
      central Ohio, this article examines perceptions of small-town life and the
      influence of local social networks on drug-using practices. Since chronic drug
      use is often driven by associations with other users, the combination of small
      social circles, a limited scope of acquaintances and economic opportunities,
      inadequate drug treatment, and abundant drug supplies can create a "vortex"
      effect and magnify drug use in small towns.

PMID- 18614388
TI  - Life-course socioeconomic environment and health risk behaviours. A multilevel
      small-area analysis of young-old persons in an urban neighbourhood in Lausanne,
      Switzerland.
AB  - With a life expectancy at the age of 65 of around 20 years, damaging health risk
      behaviours of young-old adults have become a target for preventive actions. Such
      risk factors necessitate an accurate understanding of the present and past
      socioeconomic conditions associated with health risk behaviours. The aim of our
      study is to assess the impact of certain life events as well as economic and
      environmental factors on health risk behaviours. We included 1309 participants of
      the Lausanne Cohort Lc65+ aged 65-70 years and employed logistic regression
      analyses, with individuals nested within areas. The results illustrate the
      influences of socioeconomic factors from childhood to young-old age. Life
      experiences in adulthood and economic resources in young-old age are both
      associated with unfavourable health behaviours. Neighbourhood is a modest
      determinant as well, particularly regarding alcohol consumption. Therefore,
      prevention against health risk behaviours should focus on population subgroups
      defined on the basis of their socioeconomic and living contexts.

PMID- 18614389
TI  - Chemically modified siRNA: tools and applications.
AB  - Chemical modification provides solutions to many of the challenges facing siRNA
      therapeutics. This review examines the various siRNA modifications available,
      including every aspect of the RNA structure and siRNA duplex architecture. The
      applications of chemically modified siRNA are then examined, with a focus on
      specificity (elimination of immune effects and hybridization-dependent off-target
      effects) and delivery. We also discuss improvement of nuclease stability and
      potency.

PMID- 18614390
TI  - Decision making, movement planning and statistical decision theory.
AB  - We discuss behavioral studies directed at understanding how probability
      information is represented in motor and economic tasks. By formulating the
      behavioral tasks in the language of statistical decision theory, we can compare
      performance in equivalent tasks in different domains. Subjects in traditional
      economic decision-making tasks often misrepresent the probability of rare events
      and typically fail to maximize expected gain. By contrast, subjects in
      mathematically equivalent movement tasks often choose movement strategies that
      come close to maximizing expected gain. We discuss the implications of these
      different outcomes, noting the evident differences between the source of
      uncertainty and how information about uncertainty is acquired in motor and
      economic tasks.

PMID- 18614391
TI  - Phosphate starvation signaling: a threesome controls systemic P(i) homeostasis.
AB  - Systemic signaling between roots and shoots is required to maintain mineral
      nutrient homeostasis for optimal metabolism under varying environmental
      conditions. Recent work has revealed molecular components of a signaling module
      that controls systemic phosphate homeostasis, modulates uptake and transport in
      Arabidopsis. This module comprises PHO2, a protein that controls protein
      stability, the phloem-mobile microRNA-399 and a ribo-regulator that squelches the
      activity of miR399 towards PHO2 by a novel mechanism. This advance is a
      significant step for the design of future rational approaches to improve crop
      phosphate use efficiency.

PMID- 18614392
TI  - Genomes, free radicals and plant cell invasion: recent developments in plant
      pathogenic fungi.
AB  - This review describes current advances in our understanding of fungal-plant
      interactions. The widespread application of whole genome sequencing to a diverse
      range of fungal species has allowed new insight into the evolution of fungal
      pathogenesis and the definition of the gene inventories associated with important
      plant pathogens. This has also led to functional genomic approaches to carry out
      large-scale gene functional analysis. There has also been significant progress in
      understanding appressorium-mediated plant infection by fungi and its underlying
      genetic basis. The nature of biotrophic proliferation of fungal pathogens in host
      tissue has recently revealed new potential mechanisms for cell-to-cell movement
      by invading pathogens.

PMID- 18614393
TI  - Systemic acquired resistance: the elusive signal(s).
AB  - Systemic acquired resistance (SAR) is a form of inducible resistance that is
      triggered in systemic healthy tissues of locally infected plants. The nature of
      the mobile signal that travels through the phloem from the site of infection to
      establish systemic immunity has been sought after for decades. Several candidate
      signaling molecules have emerged in the past two years, including the methylated
      derivative of a well-known defense hormone (methyl salicylate), the defense
      hormone jasmonic acid, a yet undefined glycerolipid-derived factor, and a group
      of peptides that is involved in cell-to-cell basal defense signaling. Systemic
      SAR signal amplification increasingly appears to parallel salicylic acid
      dependent defense responses, and is concomitantly fine-tuned by auxin.

PMID- 18614394
TI  - Many different tumor types have polyclonal tumor origin: evidence and
      implications.
AB  - Few ideas have gained such strong acceptance in the scientific community as the
      monoclonal origin of tumors; the idea that tumors start with a single mutated
      cell (or a single clone of cells) that go on to accumulate additional mutations
      as a tumor develops. The certainty with which this concept is held by the
      scientific community reflects the length of time it has been unchallenged and the
      experimental difficulty in obtaining direct evidence to the contrary. Yet, recent
      findings regarding X chromosome inactivation patch size indicate that the X
      linked marker data previously interpreted as evidence of monoclonal tumor origin
      is actually more consistent with polyclonal tumor origin, a situation where two
      or more cells or clones of cells interact to initiate a tumor. Although most
      tumors show homotypy for X-linked markers (as expected given the bias conferred
      by X chromosome inactivation patch size), the literature contains numerous
      examples of tumors with X-linked marker heterotypy, examples of which encompass
      24 different tumor types. Chimeric models have yielded direct unequivocal
      demonstrations of polyclonality in rodent and human tumors. Also, mutational data
      are consistent with polyclonal tumor origin. Methods that analyze levels of tumor
      associated oncogene and tumor suppressor gene mutations demonstrate that
      initiated cells are much more common in normal tissues than previously realized.
      Also, while tumors have higher levels of mutation than normal tissues, oncogenic
      mutations frequently are present as subpopulations within tumors, rather than as
      the pure mutant populations expected to develop from a single initiated cell.
      Understanding the mutational basis of tumor etiology has important practical
      significance for assessing cancer risk, as well as in modeling and treating
      cancer. Therefore, the scientific community needs to re-examine this issue and
      consider the implications of polyclonal origin for, perhaps, a majority of
      tumors, encompassing many different tumor types.

PMID- 18614395
TI  - Implementation of a query interface for a generic record server.
AB  - INTRODUCTION: This paper presents work to define a representation for clinical
      research queries that can be used for the design of generic interfaces to
      electronic healthcare record (EHR) systems. Given the increasing prevalence of
      EHR systems, with the potential to accumulate life-long health records,
      opportunities exist to analyse and mine these for new knowledge. This potential
      is presently limited by many factors, one of which is the challenge of extracting
      information from them in order to execute a research query. METHOD: There is
      limited pre-existing work on the generic specification of clinical queries. Sets
      of example queries were obtained from published studies and clinician reference
      groups. These were re-represented as structured logical expressions, from which a
      generalisable pattern (information model) was inferred. An iterative design and
      implementation approach was then pursued to refine the model and evaluate it.
      RESULTS: This paper presents a set of requirements for the generic representation
      of clinical research queries, and an information model to represent any arbitrary
      such query. A middleware component was implemented as an interface to an existing
      system that holds 20,000 anonymised cancer EHRs in order to validate the model.
      This component was interfaced in turn to a query design and results presentation
      tool developed by the Open University, to permit end user demonstrations and
      feedback as part of the evaluation. CONCLUSION: Although it is difficult to
      separate cleanly the evaluation of a theoretical model from its implementation,
      the empirical evaluation of the query-execution interface revealed that clinical
      queries of the kinds studied could all be represented and executed successfully.
      However, performance was a problem and this paper outlines some of the challenges
      faced in building generic components to handle specialised data structures on a
      large scale. The limitations of this work are also discussed. The work
      complements many years of European research and standardisation on the
      interoperable communication of electronic health records, by proposing a way in
      which one or more EHR systems might be queried in a standardised way.

PMID- 18614396
TI  - Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti
      TNFalpha therapy.
AB  - BACKGROUND: Cytomegalovirus infection and disease is associated with poor
      prognosis and steroid refractoriness in inflammatory bowel disease patients. The
      unfavourable effect of steroids and immunosuppressive therapy on CMV infection is
      well known but few data are available concerning anti-TNFalpha therapy
      (Infliximab). Aim of the study was to evaluate the presence and severity of CMV
      infection and disease in Infliximab-treated IBD patients. PATIENTS AND METHODS:
      The severity of active CMV infection and disease was assessed in 11 consecutive
      patients with ileocolonic/colonic disease and 4 patients with ulcerative colitis
      before and after a standard 3-infusion course of Infliximab. Active CMV infection
      was evaluated by serology and diagnosed by means of pp65-antigenemia (pp65 AG),
      and quantification of CMV DNA isolated from biopsy specimens of colonic tissue.
      CMV disease was assessed on haematoxylin/eosin-stained colonic biopsies and
      immunohistochemical stains. RESULTS: Of the 11 patients, nine were CMV
      seropositive. As far as concerns CMV infection, only one patient had positive
      pp65 AG, before and after Infliximab. CMV DNA was detected in the colonic
      biopsies of three patients. In 2, CMV DNA persisted also after therapy with 410
      and 1300 copies/microg of DNA, respectively, albeit with no evidence of worsening
      of the colonic disease. In the remaining patient, CMV DNA load became
      undetectable. Conventional histology and immunohistochemical stains were negative
      for CMV in all the patients, without evidence of CMV disease. CONCLUSIONS: Active
      CMV infection did not progress to disease following Infliximab therapy. Although
      these preliminary observations require confirmation, the response to Infliximab
      therapy does not appear to be influenced by, or influence the course of, CMV
      infection/disease.

PMID- 18614397
TI  - Type D personality and depressive symptoms are independent predictors of impaired
      health status in chronic heart failure.
AB  - OBJECTIVE: To examine whether Type D personality exerts a stable, independent
      effect on health status in CHF over time, adjusted for depressive symptoms.
      SUBJECTS: CHF outpatients (n=166; 75% men; mean age 66 years) completed the Type
      D Scale and Beck Depression Inventory (baseline) and the Minnesota Living with
      Heart Failure Questionnaire and Short-Form Health Survey (baseline and 12
      months). RESULTS: There was a general improvement in disease-specific physical
      (p=.029) and mental (p<.001) health over time, but Type D patients scored
      significantly lower on both outcomes (p<or=.001). The interaction effects Type D
      x time were not significant, indicating stability of the personality effect. Type
      D patients also scored significantly lower on all generic physical (p values
      between .001 and .04) and mental (all p values <.001) health status subdomains;
      these effects were also stable over time. Type D was an independent predictor of
      disease-specific mental health (p<.001), social functioning (p=.04), role
      emotional functioning (p<.001), bodily pain (p=.05), and general health (p=.04),
      adjusted for depressive symptoms, baseline health status and clinical
      characteristics. Depressive symptom was an independent predictor of role physical
      functioning and bodily pain. CONCLUSIONS: Type D personality and depressive
      symptoms were independent predictors of impaired health status in CHF.

PMID- 18614398
TI  - Sleep disordered breathing in patients with acutely decompensated heart failure.
AB  - OBJECTIVE: The purpose of this study is to systematically characterize sleep
      disordered breathing (SDB) during acute heart failure (HF) decompensation.
      BACKGROUND: SDB, both Cheyne-Stokes breathing (CSB) and obstructive sleep apnea,
      is common in stable congestive HF patients, but its presence and characteristics
      in decompensated HF is unknown. METHODS: Eighteen men and 11 women (mean age 57+/
      17 years, plasma brain-natriuretic peptide 1660+/-1179pg/ml, left ventricular
      ejection fraction 20+/-6%) admitted with decompensated systolic HF without other
      active cardiorespiratory morbidity underwent echocardiography and overnight
      bedside polysomnography within 48h of admission. Ten patients underwent follow-up
      polysomnography just before or immediately after hospital discharge. RESULTS:
      Twenty-eight of 29 patients demonstrated an apnea+hypopnea index (AHI)>5 events/h
      (mean AHI 41+/-29/h); 22 patients had an AHI>15/h. SDB was predominantly CSB
      (central events 39+/-29/h; obstructive events 2+/-2/h, p<0.001). Time in CSB was
      51+/-33% of total sleep time (TST); nadir oxygen saturation (SaO2) was 81+/-10%.
      SDB was similar on admission vs. follow-up polysomnography (mean AHI 44+/-39/h
      vs. 38+/-31/h; CSB 53+/-38% vs. 46+/-37% TST). Follow-up polysomnography showed a
      higher nadir SaO2 than admission (84+/-11% vs. 79+/-12%, p=0.05), but TST with
      SaO2<90% was not reduced. CONCLUSIONS: CSB is common and severe in patients
      hospitalized with decompensated HF. Acute treatment of HF does not consistently
      improve CSB. The effect of CSB on ventricular function and prognosis in
      decompensated HF remains to be demonstrated.

PMID- 18614399
TI  - New dimensions in tumor immunology: what does 3D culture reveal?
AB  - Experimental models indicate that tumor cells in suspension, unlike solid tumor
      fragments, might be unable to produce life-threatening cancer outgrowth when
      transferred to animal models, irrespective of the number of cells transferred,
      although they induce specific immune responses. Human tumor cells cultured in
      three dimensions display increased pro-angiogenic capacities and resistance to
      interferons, chemotherapeutic agents or irradiation, as compared with cells
      cultured in two-dimensional (2D) monolayers. Tumor cells cultured in three
      dimensions were also shown to be characterized by defective immune recognition by
      cytotoxic T lymphocytes (CTLs) specific for tumor-associated antigens (TAAs) and
      by a capacity to inhibit CTL proliferation and dendritic cell (DC) functions.
      Downregulation of human leukocyte antigen (HLA) or TAA expression and high
      production of lactic acid might play a role in the elicitation of these effects.
      Here, we propose that growth in 3D architectures might provide new insights into
      tumor immunology and could represent an integral missing component in
      pathophysiological tumor immune escape mechanisms.

PMID- 18614400
TI  - IFN-gamma treated monocyte/macrophage phagocytosis of red cells sensitized with
      IgG1 and IgG3 Anti-D containing identical immunoglobulin variable region genes.
AB  - Cytokines play a major role in the immune response by activating mononuclear
      phagocytes. The aim of this study was to determine the effects of cytokines on Fc
      gamma receptor (FcgammaR)-mediated phagocytosis of IgG1- or IgG3-sensitized red
      blood cells (RBCs). The results show a large variation in human monocyte
      phagocytosis independent of IgG subclass. The work suggests that current markers
      used to predict immune-mediated extravascular hemolysis (e.g. ITP or HDN), such
      as antibody amount/titre or immunoglobulin subclass, fail to take into account
      the immune environment. Of the cytokines studied, monocytes displayed a clear
      dose-dependant increased phagocytic response to interferon-gamma (IFN-gamma).
      More importantly, using anti-D with identical immunoglobulin variable region
      genes, but either IgG1 or IgG3 heavy chain isotopes, the change in phagocytosis
      can increase fourfold after cytokine treatment. Previous studies have shown an
      important role of FcgammaR II and III recruitment in phagocytosis and the
      importance of IgG subclass interactions with FcgammaR allotypic variants. There
      is an increased interest in effects of IFN-gamma on monocyte phagocytosis in the
      context of proinflammatory disease states. Future aims are directed towards
      identifying cytokine variants that regulate monocyte phagocytosis.

PMID- 18614401
TI  - The six questions of pathogen reduction technology: an overview of current
      opinions.
AB  - The current measures to ensure blood safety include: donor selection,
      conventional serology testing for infectious markers by ELISA and NAT,
      leukoreduction, UV/Gamma irradiation and pathogen reduction technologies (PRT).
      These measures offer some conceptual assurance on continual improvement in blood
      safety, but with respect to PRT, there are at least six unresolved questions [6
      Qs] that still need to be addressed to make them universally acceptable. The
      current status of PRT for plasma, platelets and red blood cells is explored
      through comparative analyses, in tabulated format, to help in answering the
      questions posed by the authors of this overview.

PMID- 18614403
TI  - Antihypertensive treatment and dementia prevention.

PMID- 18614404
TI  - Disruption of Nrf2 enhances susceptibility to airway inflammatory responses
      induced by low-dose diesel exhaust particles in mice.
AB  - To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative
      stress and host antioxidant responses play a key role in the development of DEP
      induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related
      factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose
      DEP for 7 h/day, 5 days/week, for 8 weeks. Nrf2(-/-) mice exposed to low-dose DEP
      showed significantly increased airway hyperresponsiveness and counts of
      lymphocytes and eosinophils, together with increased concentrations of IL-12 and
      IL-13, and thymus and activation-regulated chemokine (TARC), in BAL fluid than
      wild-type mice. In contrast, expression of antioxidant enzyme genes was
      significantly higher in wild-type mice than in Nrf2(-/-) mice. We have first
      demonstrated that disruption of Nrf2 enhances susceptibility to airway
      inflammatory responses induced by inhalation of low-dose DEP in mice. These
      results strongly suggest that DEP-induced oxidative stress and host antioxidant
      responses play some role in the development of DEP-induced airway inflammation.

PMID- 18614405
TI  - How to prevent, recognize, and manage complications of lead extraction. Part III:
      Procedural factors.

PMID- 18614406
TI  - An electro-catalytic biosensor fabricated with Pt-Au nanoparticle-decorated
      titania nanotube array.
AB  - A Gold-Platinum nanoparticle-decorated titania nanotubular electrode is
      fabricated by electrochemically depositing Au and Pt nanoparticles onto a highly
      oriented titania nanotube array. The prepared electrode, characterized by SEM and
      EDX, shows remarkably improved catalytic activities in the oxidation of hydrogen
      peroxide. By modifying the electrode with glucose oxidase (GOx) the resultant
      glucose biosensor exhibits a high sensitivity to glucose in the range of 0 to 1.8
      mM with a response time of 3 s and detection limit of 0.1 mM.

PMID- 18614402
TI  - Incident dementia and blood pressure lowering in the Hypertension in the Very
      Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Observational epidemiological studies have shown a positive
      association between hypertension and risk of incident dementia; however, the
      effects of antihypertensive therapy on cognitive function in controlled trials
      have been conflicting, and meta-analyses of the trials have not provided clear
      evidence of whether antihypertensive treatment reduces dementia incidence. The
      Hypertension in the Very Elderly trial (HYVET) was designed to assess the risks
      and benefits of treatment of hypertension in elderly patients and included an
      assessment of cognitive function. METHODS: Patients with hypertension (systolic
      pressure 160-200 mm Hg; diastolic pressure <110 mm Hg) who were aged 80 years or
      older were enrolled in this double-blind, placebo-controlled trial. Participants
      were randomly assigned to receive 1.5 mg slow release indapamide, with the option
      of 2-4 mg perindopril, or placebo. The target systolic blood pressure was 150 mm
      Hg; the target diastolic blood pressure was 80 mm Hg. Participants had no
      clinical diagnosis of dementia at baseline, and cognitive function was assessed
      at baseline and annually with the mini-mental state examination (MMSE). Possible
      cases of incident dementia (a fall in the MMSE score to <24 points or a drop of
      three points in 1 year) were assessed by standard diagnostic criteria and expert
      review. The trial was stopped in 2007 at the second interim analysis after
      treatment resulted in a reduction in stroke and total mortality. Analysis was by
      intention to treat. The trial is registered with ClinicalTrials.gov, number
      NCT00122811. FINDINGS: 3336 HYVET participants had at least one follow-up
      assessment (mean 2.2 years) and were included: 1687 participants were randomly
      assigned to the treatment group and 1649 to the placebo group. Only five reports
      of adverse effects were attributed to the medication: three in the placebo group
      and two in the treatment group. The mean decrease in systolic blood pressure
      between the treatment and placebo groups at 2 years was systolic -15 mm Hg,
      p<0.0001; and diastolic -5.9 mm Hg, p<0.0001. There were 263 incident cases of
      dementia. The rates of incident dementia were 38 per 1000 patient-years in the
      placebo group and 33 per 1000 patient-years in the treatment group. There was no
      significant difference between treatment and placebo groups (hazard ratio [HR]
      0.86, 95% CI 0.67-1.09); however, when these data were combined in a meta
      analysis with other placebo-controlled trials of antihypertensive treatment, the
      combined risk ratio favoured treatment (HR 0.87, 0.76-1.00, p=0.045).
      INTERPRETATION: Antihypertensive treatment in elderly patients does not
      statistically reduce incidence of dementia. This negative finding might have been
      due to the short follow-up, owing to the early termination of the trial, or the
      modest effect of treatment. Nevertheless, the HYVET findings, when included in a
      meta-analysis, might support antihypertensive treatment to reduce incident
      dementia.

PMID- 18614407
TI  - Tetrodotoxin poisoning evidenced by solid-phase extraction combining with liquid
      chromatography-tandem mass spectrometry.
AB  - The toxicity and toxin component of gastropod Niotha clathrata implicated to a
      food paralytic poisoning incident in Kaohsiung, Taiwan in November 2006 were
      studied. The highest scores of average toxicity in the digestive gland and other
      portions from collected gastropods were 62+/-24 (mean+/-S.D.) and 32+/-16
      microg/g according to tetrodotoxin (TTX) bioassay, respectively. The toxin from
      these gastropods was large amount and easily identified as tetrodotoxin by
      traditional method of HPLC-FLD. The toxin of patient's blood serum was trace
      amount and analyzed by a new developed method LC-MS/MS. LC-MS/MS was contracted
      by the LC system interfaced with the MS/MS system with a turbo ion spray
      interface. Positive ion detection and multiple reaction monitoring mode were used
      for TTX of patient serum. It was found that linearity in serum was observed
      within concentration ranged of 1-100 ng/ml and limit of detection was 0.1 ng/ml.
      The LOQ was reproducible at 1 ng/ml in serum. The blood serum showed to contain
      TTX of 3.30+/-0.08 ng/ml. It indicated that LC-MS/MS was more lower detectable
      and believable method for TTX determination than LC-MS reported previously.
      Furthermore, the causative agent of gastropod food poisoning was identified as
      TTX.

PMID- 18614409
TI  - NOTES: The next surgical revolution?

PMID- 18614408
TI  - Liquid chromatography/tandem mass spectrometry method for simultaneous evaluation
      of activities of five cytochrome P450s using a five-drug cocktail and application
      to cytochrome P450 phenotyping studies in rats.
AB  - A reliable liquid chromatography/tandem mass spectrometry has been developed for
      simultaneous evaluation of the activities of five cytochrome P450s (CYP1A2,
      CYP2C9, CYP2C19, CYP2D6, and CYP3A) in rat plasma and urine. The five-specific
      probe substrates/metabolites include phenacetin/paracetamol (CYP1A2),
      tolbutamide/4-hydroxytolbutamide and carboxytolbutamide (CYP2C9), mephenytoin/4'
      hydroxymephenytoin (CYP2C19), dextromethorphan/dextrorphan (CYP2D6), and
      midazolam/1'-hydroxymidazolam (CYP3A). Internal standards were brodimoprim (for
      phenacetin, paracetamol, midazolam and 1'-hydroxymidazolam), ofloxacin (for 4'
      hydroxymephenytoin, dextromethorphan and dextrorphan) and meloxicam (for
      tolbutamide, 4-hydroxytolbutamide and carboxytolbutamide). Sample preparation was
      conducted with solid-phase extraction using Oasis HLB cartridges. The
      chromatography was performed using a C(18) column with mobile phase consisting of
      methanol/0.1% formic acid in 20 mM ammonium formate (75:25). The triple
      quadrupole mass spectrometric detection was operated in both positive mode (for
      phenacetin, paracetamol, midazolam, 1'-hydroxymidazolam, brodimoprim, 4'
      hydroxymephenytoin, dextromethorphan, dextrorphan and ofloxacin) and negative
      mode (for tolbutamide, 4-hydroxytolbutamide, carboxytolbutamide and meloxicam).
      Multiple reaction monitoring mode was used for data acquisition. Calibration
      ranges in plasma were 2.5-2500 ng/mL for phenacetin, 2.5-2500 ng/mL for
      paracetamol, 5-500 ng/mL for midazolam, and 0.5-500 ng/mL for 1'
      hydroxymidazolam. In urine calibration ranges were 5-1000 ng/mL for
      dextromethorphan, 0.05-10 microg/mL for dextrorphan and 4'-hydroxymephenytoin, 5
      2000 ng/mL for tolbutamide, 0.05-20 microg/mL for 4-hydroxytolbutamide and 0.025
      10 microg/mL for carboxytolbutamide. The intra- and inter-day precision were 4.3
      12.4% and 1.5-14.8%, respectively for all of the above analytes. The intra- and
      inter-day accuracy ranged from -9.1 to 8.3% and -10 to 9.2%, respectively for all
      of the above analytes. The lower limits of quantification were 2.5 ng/mL for
      phenacetin and paracetamol, 5 ng/mL for midazolam, 0.5 ng/mL for 1'
      hydroxymidazolam, 5 ng/mL for dextromethorphan, 50 ng/mL for dextrorphan and 4'
      hydroxymephenytoin, 5 ng/mL for tolbutamide, 50 ng/mL for 4-hydroxytolbutamide
      and 25 ng/mL for carboxytolbutamide. All the analytes were evaluated for short
      term (24 h, room temperature), long-term (3 months, -20 degrees C), three freeze
      thaw cycles and autosampler (24 h, 4 degrees C) stability. The stability of urine
      samples was also prepared with and without beta-glucuronidase incubation (37
      degrees C) and measured comparatively. No significant loss of the analytes was
      observed at any of the investigated conditions. The current method provides a
      robust and reliable analytical tool for the above five-probe drug cocktail, and
      has been successfully verified with known CYP inducers.

PMID- 18614410
TI  - Reverse dorsolateral proximal phalangeal island flap: a new versatile technique
      for coverage of finger defects.
AB  - All flaps described for the reconstruction of finger defects have limited
      indications and many disadvantages. In this study, I successfully developed a
      reverse digital artery flap raised from the overall side and dorsal aspects of
      the proximal phalanx, excluding the digital nerve, for closure of fingertip and
      middle phalangeal defects, and called this the 'reverse dorsolateral proximal
      phalangeal island flap'. The donor site defect was covered by another flap called
      the 'dorsal metacarpal V-Y island flap'. The method was used for 12 complicated
      phalangeal defects in 11 patients. Flap sizes ranged from 2 x 1.5 cm to 3 x
      2.5cm. The flap was applied with versatile designs including distal
      interphalangeal (DIP) (9) or proximal interphalangeal (PIP) anastomoses-based
      flaps (3); homodigital (10) or heterodigital flaps (2) from the injuries or
      adjacent finger, respectively; multiple flaps from the two distinct fingers in
      the same hand (1); and a sensate flap (1). The average follow-up time was 11.5
      months. All reverse flaps and V-Y donor site flaps survived completely. Finger
      lengths and motions were satisfactory with favourable aesthetic results in all
      cases. The mean value of static two-point discrimination was 9.3mm. I strongly
      advocate this new flap, as a single versatile flap, for repair of different-sized
      or complex phalangeal defects. By means of this 'dual-flap manoeuvre', any defect
      distal to the PIP joint in various dimensions can safely be covered without using
      a skin graft in the donor area. I also suggest the dorsal metacarpal V-Y island
      flap alone for dorsal phalangeal defects proximal to this point.

PMID- 18614411
TI  - Sternal wound dehiscence complicated by macromastia: report of two cases with
      discussion of literature.
AB  - Sternal wound dehiscence complicated by macromastia can be difficult to treat by
      standard musculocutaneous flaps alone. We present our experience with two cases
      of sternal wound dehiscence complicated by macromastia, and their subsequent
      healing with a combination of reduction mammoplasty and local musculocutaneous
      flaps. Reduction mammoplasty is a useful adjunctive procedure in patients with
      macromastia complicating sternal wound dehiscence.

PMID- 18614412
TI  - [Doppler US of the urinary system and renal vessels in normal and pathologic
      conditions].
AB  - The interest of Doppler ultrasound (US) in urinary tract investigation has
      dramatically increased during the past 10 years. It can provide useful diagnostic
      informations in pedicular and intrarenal vascular disorders, some medical
      nephropathies, in the assessment of renal tumors and urinary tract disorders
      including urolithiasis, acute obstruction and ureteral reflux. Recent technical
      improvements including the development of US contrast agents (microbubbles) have
      contributed to increase the diagnostic accuracy of the technique.

PMID- 18614413
TI  - Cardioprotective effects and mechanism of action of polyphenols extracted from
      propolis against doxorubicin toxicity.
AB  - Propolis is one of the major hive products of bees and is rich in flavonoids,
      which are known for antioxidant activities. It is well known that the chemical
      properties of phenolic acids or flavonoids, in terms of the availability of the
      phenolic hydrogens as hydrogen donating radical scavengers, predict their
      antioxidant properties. In this study, the flavonoids scavenging activity of
      propolis has been exploited to obtain protection against the peroxidative damage
      in rat heart mitochondria which was induced by the administration of an acute
      dose of doxorubicin (20 mg kg(-1), i.p). The peroxidative lesions were evaluated
      biochemically and biophysically, 24 H after DXR administration. Abnormal
      biochemical changes in heart mitochondria from DXR treated rats including a
      marked increase in both malondialdehyde (MDA) and anion superoxide production;
      decrease both of respiratory chain ratio (RCR= V3/V4) and P/O. Pretreatment of
      rats with propolis extract, given per os (100 mg/kg/day) during four days prior
      to DXR injection, substantially reduced the peroxidative damage in the heart
      mitochondria: we showed significant reducing both of mitochondrial MDA formation
      and production of superoxide anion, restoration of RCR and P/O and reducing of
      rate and the amplitude of mitochondrial swelling. The data demonstrate that
      antioxidants from natural sources may be useful in the protection of
      cardiotoxicity in patients who receive doxorubicin and as reported for its
      claimed beneficial effect on human health by biomedical literature.

PMID- 18614414
TI  - Antibacterial activity of Thymus daenensis methanolic extract.
AB  - Medicinal plants are potential of antimicrobial compounds. The present study
      deals with the antibacterial activity of methanolic extract of Thymus daenensis.
      Aerial parts of the plant were collected from Alvand mountainside (Hamadan, Iran)
      in May 2005, air-dried and extracted by methanol. The dried extract was
      redissolved in methanol to make a 100 mg/ml solution and then filtered.
      Antibacterial activity of the extract was evaluated against various Gram-positive
      and Gram-negatives bacteria using disk diffusion technique. Blank paper disks
      were loaded with 40 microl of the methanol solution and then dried up. The
      impregnated disks were placed on Mueller-Hinton agar inoculated with bacterial
      suspension equal to 0.5 McFarland. The extract inhibited the growth Gram-positive
      bacteria, i.e., Staphylococcus aureus, Micrococcus luteus, Entrococcus faecalis,
      Streptococcus pyogenes, but it showed no activity against Gram-negative bacteria.
      The most significant effect was seen against S.aureus including MRSA, which are
      important nosocomial pathogens. MIC90 of the extract was determined against Gram
      positive bacteria (3.12 mg/ml) and 11 MRSA strain (1.56 mg/ml).

PMID- 18614415
TI  - Chemometric determination of rabeprazole sodium in presence of its acid induced
      degradation products using spectrophotometry, polarography and anodic voltammetry
      at a glassy carbon electrode.
AB  - Chemometric stability indicating methods are presented for the determination of
      rabeprazole sodium in presence of its acid induced degradation products using
      spectrophotometry, differential pulse polarography and differential pulse anodic
      voltammetry at a glassy carbon electrode. The applied chemometric techniques are
      multivariate ones including classical least squares (CLS), principal component
      regression (PCR) and partial least squares (PLS). A difference spectrophotometric
      (DeltaA) method has also been applied. To develop the multivariate calibrations,
      a training set was used, consisting of 20 mixture solutions of rabeprazole sodium
      and its degradation products. These mixtures show percentage degradation ranging
      from 0.5-65%, 0.5-95% and 0.6-75% for the spectrophotometric, polarographic and
      anodic voltammetric calibrations, respectively. The UV absorbances were recorded
      in 0.1 M NaOH within the wavelength range 220-340 nm at 2 nm intervals. The
      polarograms and anodic voltammograms were recorded in Britton-Robinson buffer (pH
      8.0) within the potential range -500 to -1508 and 400 to 1192 mV at 6 mV
      intervals with a pulse amplitude of -100 and 50 mV, sweep rate of 15 and 10 mV s(
      1) and pulse interval of 0.4 and 0.6 s for the polarographic and anodic
      voltammetric methods, respectively. All the studied methods have been validated
      and successfully applied to the determination of rabeprazole sodium in tablet
      dosage form. The results were statistically compared to those obtained using a
      published HPLC method. No significant difference has been found.

PMID- 18614416
TI  - Pharmacokinetics of ciprofloxacin in normal rabbits and changes observed in
      induced dehydrated state.
AB  - The pharmacokinetics of ciprofloxacin following oral administration of a single
      dose of 20 mg/kg body weight was investigated in normal rabbits and changes were
      observed in water-deprived rabbits. High performance liquid chromatographic
      method was employed for the determination of plasma concentration of
      ciprofloxacin. The mean plasma concentration and AUC (0-t) and AUC (0-inf) were
      significantly different between normal and dehydrated rabbits (P<0.05), but the
      absorption rate, distribution rate, and elimination rate did not show any
      statistically significant difference. The results reflect a need for monitoring
      toxicity of ciprofloxacin in the water-deprived condition.

PMID- 18614417
TI  - A comparative study of dissolution characteristics of polymeric and wax
      granulations of theophylline and their tablets.
AB  - Matrix (non disintegrating) granules of theophylline have been formed and their
      dissolution characteristics investigated for sustained release application. The
      polymeric granulations were formed by massing the drug powder with a concentrated
      (40% w/w) ethanolic solution of an acrylatemethacrylate copolymer (ERS100R). Wax
      granulations were also formed by massing the drug powder with previously melted
      carnuba wax followed by screening and drying. The content of polymer or wax in
      the resulting granules was 16.7% w/w. Conventional granules of theophylline were
      formed by massing the drug powder with starch mucilage (20% w/v). Resulting
      granules were subjected to particle size analysis and in vitro dissolution tests.
      The granules were further compressed to tablets (weight 500+/-4.2 mg each) at a
      constant load (30 arbitrary units on the load scale). The tablets were subjected
      to hardness, disintegration and dissolution tests. The dissolution kinetics were
      also considered. The mean granule size was 646.5+/-4.3 microm (conventional),
      821.4+/-4.8 microm (polymeric granulations) and 892.7+/-5.4 microm (wax
      granulations), the matrix granules were therefore larger than the conventional
      granules. Dissolution of the granules generally followed a first order rate
      kinetic. The rate constant (k(1)) for the conventional, polymeric and wax
      granulations were (h(-1)): 0.53, 0.31 and 0.27 respectively. Thus, the wax
      granulations appeared to be more effective than the polymeric granulations in
      retarding drug release from the granules but the difference was not statistically
      significant (p>0.05). The tensile strength of tablets derived from the
      conventional, polymeric and wax granulations were (MNm(-2)) 0.85, 1.68 and 1.96
      respectively, indicating that the matrix granules (compared with the conventional
      granules) produced harder tablets at the same compression load. The corresponding
      first order dissolution rate constants were (h(-1)): 0.46, 0.28 and 0.21. Thus,
      tableting of the matrix granules produced a slight but significant decrease in
      dissolution rates, attributable to the disintegration of the tablets to more
      compact particles.

PMID- 18614418
TI  - The effect of magnesium supplementation on glucose and insulin levels of tae-kwan
      do sportsmen and sedentary subjects.
AB  - This study was performed to determine how the magnesium supplementation for a 4
      week period affects the glucose and insulin levels at rest and at exhaustion in
      sportsmen. This is a 4 week study performed on 30 healthy male subjects varying
      between 18-22 ages. Subjects were separated into 3 groups. 1st group; group
      supplemented with magnesium, 2nd group; Magnesium supplementations exercise
      group, 3rd group; training group. Glucose and insulin parameters of the groups
      were measured 4 times; at rest and exhaustion in the beginning of the research
      and at rest and exhaustion after the end of 4 weeks application period. Glucose
      levels in exhaustion measurements both before and after the supplementation
      significantly increased compared to resting levels (p<0.05). Significant
      difference was determined in the glucose values of 1st and 2nd groups
      supplemented with magnesium in comparison to their first measurements (p<0.05).
      Insulin values a decrease in all of the 3 groups occurred with exercise both
      before and after the supplementation (p<0.05). Magnesium supplementation has an
      important effect on glucose levels whereas it has no effect on insulin levels.

PMID- 18614420
TI  - Evaluation of antioxidant properties of silymarin and its potential to inhibit
      peroxyl radicals in vitro.
AB  - Silymarin (milk thistle) has been used for centuries as a natural remedy for
      diseases of liver and biliary tract. The present study was carried out to
      evaluate the in vitro free radical scavenging activity and antioxidant properties
      of silymarin. Antioxidant properties of silymarin were evaluated by four methods:
      1) FARP assay for total antioxidant capacity; 2) DPPH radical scavenging assay;
      3) the inhibitory effect on RBC hemolysis induced by peroxyl radicals from APPH;
      4) the inhibitory effect on plasma oxidation induced by Cu(2+). But total
      phenolic compound was evaluated by Folin-Ciocalteu method. Total polyphenol
      compounds of silymarin was 0.484+/-0.017 mg Gallic acid equivalent per mg in
      comparison to that of green tea which is 0.313+/-0.095. High Antioxidant
      properties and significant protective effect of silymarin were in a concentration
      dependent manner in all methods. Therefore, silymarin is a powerful antioxidant
      herbal drug which can protect biological systems against the oxidative stress. It
      is suggested that silymarin may be used in preventing free radical-related
      diseases as a dietary natural antioxidant supplement.

PMID- 18614419
TI  - Design and in vivo evaluation of carvedilol buccal mucoadhesive patches.
AB  - The buccal region offers an attractive route of administration for systemic drug
      delivery. Carvedilol (dose, 3.125-25 mg) is beta-adrenergic antagonist. Its oral
      bioavailability is 25-35% because of first pass metabolism. Buccal absorption
      studies of a carvedilol solution in human volunteers showed 32.86% drug
      absorption. FTIR and UV spectroscopic methods revealed that there was no
      interaction between carvedilol and polymers. Carvedilol patches were prepared
      using HPMC, carbopol 934, eudragit RS 100, and ethylcellulose. The patches were
      evaluated for their thickness uniformity, folding endurance, weight uniformity,
      content uniformity, swelling behaviour, tensile strength, and surface pH. In
      vitro release studies were conducted for carvedilol-loaded patches in phosphate
      buffer (pH, 6.6) solution. Patches exhibited drug release in the range of 86.26
      to 98.32% in 90 min. Data of in vitro release from patches were fit to different
      equations and kinetic models to explain release profiles. Kinetic models used
      were zero and first-order equations, Hixon-Crowell, Higuchi, and Korsmeyer-Peppas
      models. In vivo drug release studies in rabbits showed 90.85% of drug release
      from HPMC-carbopol patch while it was 74.63 to 88.02% within 90 min in human
      volunteers. Good correlation among in vitro release and in vivo release of
      carvedilol was observed.

PMID- 18614421
TI  - Protective effect of captopril against cisplatin-induced nephrotoxicity in rats.
AB  - This study has been initiated to determine whether captopril, an angiotensin
      converting enzyme (ACE) inhibitor containing sulfhydryl (-SH) group can protect
      against cisplatin-induced nephrotoxicity in rats. A single dose of cisplatin (7.5
      mg/kg bwt) injected i.p. caused a significant increase in blood urea nitrogen
      (BUN) and creatinine levels amounting to 402% and 573%, respectively with a
      marked elevation in lipid peroxides measured as malondialdehyde (MDA) content
      (54%), accompanied by a significant decrease in reduced glutathione (GSH) content
      (27%) of kidney tissue as compared to control group. In addition, there were
      marked increases in kidney tissue content of nitric oxide (NO) (43%) and plasma
      endothelin-1(ET-1) (37%). On the other hand, administration of captopril (60
      mg/kg bwt, i.p.) 1 h before cisplatin protected the kidney as indicated by
      restoration of BUN, creatinine, MDA, GSH, NO and ET-1. These results indicate
      that captopril, an ACEI, has a protective effect against cisplatin-induced damage
      to kidney. This reflects the beneficial role of captopril in treatment of
      renovascular hypertention and congestive heart failure; an effect that may be
      related to its free radicals scavenging and antioxidant effects which are
      sulfhydryl dependent.

PMID- 18614422
TI  - Behavioral effects of 1-(m-chlorophenyl)piperazine (m-CPP) in a rat model of
      tardive dyskinesia.
AB  - The present study was designed to monitor the responsiveness of 5-hydroxy
      tryptamine (5-HT)-2C receptor in rats treated with haloperidol exhibiting tardive
      dyskinesia (TD). Results show that haloperidol injected at a dose of 1 mg/kg
      twice a day for two weeks elicited vacuous chewing movements (VCMs). Which
      increased in a time dependent manner following the drug administration for 3-5
      weeks. The behavioral effects of 1-(m-chlorophenyl)piperazine (m-CPP) a 5-HT-2C
      and 5-HT-1B agonist were monitored 2 days after 5 weeks of saline or haloperidol
      administration. The results show that hypophagic as well as anxiogenic-like
      effects of m-CPP are greater in repeated haloperidol than repeated saline
      injected animals, while hypolocomotive effects of m-CPP are not different in
      repeated saline and haloperidol injected animals. Results are discussed in the
      context of role of 5-HT-2C receptors in the regulation of the activity of
      dopaminergic neuron and its possible impact on elicitation of TD.

PMID- 18614423
TI  - Hepatotoxicity of carbon tetrachloride: protective effect of Gongronema
      latifolium.
AB  - The protective effect of the ethanolic extract of Gongronema latifolium (GLE) on
      carbon tetrachloride (CCI4) induced hepatic toxicity was studied. Liver enzymes
      studied included alanine aminotransferase (ALT), aspartate aminotraferase (AST),
      and alkaline phosphates (ALP). Hepatic injuries involved with possible necrosis
      which may have contributed to its possible pathogenesis was explored.
      Administration of toxicant only showed that the ALT level was significantly
      (P<0.05) increased to 345.83% when compared to control. Pretreatment with
      Gongronema latifolium extract (GLE) non-significantly (P<0.05) decreased to
      13.08% when compared to those treated with toxicant only. Also under experimental
      conditions, increasing the concentration of Gongronema latifoluim extract (GLE)
      non-significantly (P<0.05) decreased dose-dependently the level of ALT to 18.20%.
      The AST level was non-significantly (P<0.05) increased to 41.55% on treatment
      with toxicant only. Pretreatment with GLE decreased the AST level non
      significantly (P<0.05) to 25.76%. No evident increase or decrease in the level of
      ALP was observed. Treatments with toxicant showed liver cells filled with
      uniformly distributed dense small fat droplets, large nuclei, inflamed cells and
      evidence of necrosis and fibrosis. Pretreatment with 100mg/kg of the extract
      showed microvesicular fatty change with no evidence of inflammation, necrosis or
      fibrosis. The protective effect of the GLE was more pronounced in ALT and AST.
      However, the GLE has a strong modulatory effect against the hepatocellular damage
      induced by carbon tetrachloride.

PMID- 18614424
TI  - Effectiveness of sildenafil citrate (Viagra) and tadalafil (Cialis) on sexual
      responses in Saudi men with erectile dysfunction in routine clinical practice.
AB  - Satisfaction with the sexual experience is considered important when evaluating
      the impact of treatments for erectile dysfunction, yet enhanced satisfaction has
      been infrequently assessed in the sexual trials. We evaluated the efficacy of
      sildenafil vs. tadalafil, in Saudi men with erectile dysfunction and determined
      the self-based rating of medicinal preference. Sildenafil citrate (Viagra) is a
      potent inhibitor of the electrolytic enzyme type V phosphodiesterase (PDE5), in
      the corpus cavernosum and therefore increases the penile response to sexual
      stimulation. Tadalafil (Cialis) is also a PDE5 inhibitor that increases the level
      of cyclic guanosine monophosphate (cGMP) in cavernous smooth muscle cells.
      Whereas cGMP is a second messenger for the vasodilator effects of nitric oxide
      causing smooth muscle relaxation, which in turn leads to penile erection; however
      the mechanism by which cGMP stimulates relaxation of the smooth muscles remains
      to be elucidated. Both sildenafil and tadalafil have a rapid onset with the
      effectiveness up to 4 hours and 36 hours respectively. In this study subjects
      treated with 100 mg oral dose of sildenafil / 20 mg tadalafil were found to be
      associated with higher mean scores for the questions of the International Index
      of Erectile Function (IIEF). Frequency of penetration and maintenance of erection
      after sexual penetration and/or during masturbation were found to be enhanced
      significantly (p<0.001) in both sildenafil/tadalafil treated men. Similarly mean
      domain of erectile function, orgasmic function, and intercourse satisfaction also
      showed a significantly positive improvement (p/0.001) in both the treated groups
      in comparison with their age matched untreated controls. Interestingly in all the
      cases, tadalafil group showed considerably greater positive responses than the
      sildenafil group but within the same significant levels. Strikingly the sexual
      desire domain in sildenafil treated men with respect to their aged matched
      controls showed a non-significant difference, where as this difference was found
      to be highly significant in tadalafil treated group. Similarly mean scores for
      the overall satisfaction domains of the IIEF in comparison with the untreated
      subjects showed a significant positive response in the sildenafil treated group
      (p<0.001), where as tadalafil treated group showed a highly significant positive
      response (p<0.005). These findings suggest that both sildenafil and tadalafil may
      assist an individual in extending/enhancing the excitement phase or prolonging
      the sexual interaction. These studies further conclude that there is a major
      point of difference between the short-acting agent sildenafil and the longer
      acting tadalafil. This probably allows more choice about the onset of sexual
      responses with tadalafil than with sildenafil.

PMID- 18614425
TI  - Simultaneous estimation of atorvastatin and ramipril by RP-HPLC and spectroscopy.
AB  - A number of analytical methods were reported for the estimation of atorvastatin
      and ramipril from their individual dosage forms or in combination with other
      drugs (Valiyare, 2004; Vachareau and Neirinck, 2000). Here successful reverse
      phase-high performance liquid chromatographic method and spectroscopic methods
      developed then validated for the analysis of combined dosage form of atorvastatin
      and ramipril. Individual lambda-max for atorvastatin is 247 n.m and that of
      ramipril is 208 n.m. They intercept at 215 n.m which is fixed as wavelength for
      reverse phase-high performance liquid chromatographic method.

PMID- 18614426
TI  - Peripheral injection of dexamethasone modulates anxiety related behaviors in
      mice: an interaction with opioidergic neurons.
AB  - Stress and anxiety initiates a cascade of biochemical and endocrine event which
      results in behavioral and electrophysiological effects in both animals and
      humans. In this study, we investigated the effects of dexamethasone (DEX), as a
      synthetic glucocorticoid, and its interaction with opioidergic system on anxiety
      related behavior in mice. Young adult male mice were used in this study. A
      standard elevated plus-maze was used to determine anxiety levels in animal.
      Different doses of DEX (0.1, 0.5, 1, 2 and 10 mg/kg, SC) or vehicle was injected
      30 min before of evaluation. Naloxone (1 and 2 mg/kg, IP) was injected 5 min
      before the DEX (0.5 and 1 mg/kg) administration. Results indicated that DEX at
      doses of 0.5 and 1 reduced and in dose of 10 mg/kg increased anxiety related
      behaviors significantly (P<0.05 in all cases). Also pretreatment of naloxone at
      doses of 1 and 2 mg/kg attenuated the effects of lower doses of DEX on anxiety
      related behaviors. Finding above indicated that peripheral administration of
      glucocorticoids induces biphasic effects on anxiety related behaviors: anxiolytic
      effects in lower doses and anxiogenic effects in a high dose. Data also revealed
      an involvement of opioidergic system in anxiolytic effects of glucocorticoids.

PMID- 18614427
TI  - Nasal carriage of staphylococci in health care workers: antimicrobial
      susceptibility profile.
AB  - One year prospective study was evaluated to ascertain the prevalence of nasal
      carriage of potentially pathogenic bacteria in health care workers and the
      antibiotic susceptibility profile. The bacterial strains were identified by
      conventional method and the antibiotic resistance was carried out by disc
      diffusion method. The prevalence of Staphylococcus aureus, coagulase negative
      staphylococci and methicillin resistant Staphylococcus aureus were 48%, 46% and
      14% respectively. The antibiotic susceptibility pattern of these isolates
      revealed that Staphylococcus aureus were more resistant towards antibiotics than
      coagulase negative staphylococci. The most effective antibiotic for S. aureus was
      found to be vancomycin with 100% efficacy, then cephalothin 92%, ciprofloxacin
      91%, amikacin 77% and erythromycin 55%, ampicillin 11% and penicillin 3%.
      Coagulase negative staphylococci were 100% sensitive to vancomycin and
      cephalothin. Oxacillin showed 78% effectiveness; while ampicillin and penicillin,
      demonstrated 64% and 59% respectively. Doxycycline (93%), amikacin (93%), fusidic
      acid (90%) and erythromycin (92%) were effective antimicrobials.

PMID- 18614429
TI  - Assessment of bioequivalence of ciprofloxacin in healthy male subjects using
      HPLC.
AB  - Pharmacokinetics and bioequivalence studies of two brands of ciprofloxacin 500 mg
      (Ciprofloxacin & Ciproxin) were evaluated in 14 healthy male volunteers after
      oral administration. The drug was analyzed in plasma samples by using HPLC. The
      peak plasma concentrations of (2.28+/-0.04 mg/L) and (1.9+/-0.02 mg/L) was
      attained in about 1.71 hours and 2.00 hours for both Test and Reference
      ciprofloxacin, respectively. The mean +/- SE values for total area under the
      curve (AUC) were 11.91+/-0.26 and 13.11+/-0.27 h.mg/L for both test and reference
      tablets respectively. This study indicated that all the differences in
      bioequivalence parameters for both ciprofloxacin formulations are statistically
      non-significant, hence both formulations are bioequivalent.

PMID- 18614428
TI  - Anti-inflammatory activity of indanyltetrazole derivatives.
AB  - A number of indanyl tetrazolederivatives namely 5-(6'-chloroindan-1'-yl)tetrazole
      (CIT), 5-(6'-bromoindan-1'-yl)tetrazole (BIT), 5-(6'-chloroindan-1'
      yl)methyltetrazole (CIMT), 5-(6'-bromoindan-1'-yl)methyl-tetrazole (BIMT) were
      evaluated for the anti-inflammatory activity in carragennan induced rat paw edema
      in Swiss albino Wister rats for 24-hour period at the dose of 100 mg/kg of body
      weight by intraperitoneal route where phenylbutazone (PBZ) was used as the
      standard. All of these compounds exhibited inhibition on rat paw edema with peak
      actions observed following 3 hours after administration. Moreover, compounds CIMT
      and BIMT were further evaluated at dose of 50 mg/kg of body weight. Among the
      compounds, CIMT showed higher activity than others and was very close to standard
      phenylbutazone.

PMID- 18614430
TI  - A sensitive HPLC method for simultaneous estimation of tamsulosin hydrochloride
      and its impurity.
AB  - Tamsulosin hydrochloride is used to treat the symptoms of an enlarged prostate, a
      condition technically known as benign prostatic hyperplasia or BPH. The analyte
      was resolved by using mobile phase (potassium dihydrogen orthophosphate and
      acetonitrile) at the flow rate of 1.2 Ml/Min. on isocratic HPLC system consisting
      of Jasco Make UV visible detector of model UV 1575 and Jasco make HPLC pump of
      model PU 1580. An ODS C-8 RP column (4.6 mm ID, 250 mm L, particle size 5 micron,
      at wavelength of 280 Nm. The linearity range was found to be 0.4 Ml/Ml for
      tamsulosin and 0.12 mg/ml to 2.0 mg/ml for its impurity. The proposed method is
      simple, accurate, rapid and selective. Percent relative standard deviation was
      found to be very low, below 2.0%, which indicates that method is highly precise
      and specific. Short analysis time (<10 min.) coupled with simplicity and ease of
      operation warrants use of the given method for analysis of tamsulosin
      hydrochloride along with its impurity as stated above in bulk. Therefore, method
      can be useful in routine quality control analysis in bulk drugs.

PMID- 18614431
TI  - Report: prevalence and resistance pattern of Pseudomonas aeruginosa against
      various antibiotics.
AB  - A prospective study on various clinical isolates from patients admitted from
      various parts of NWFP and Afghanistan at Post Graduate Medical Institute (PGMI)
      Hayatabad Medical Complex, Peshawar was conducted from January 2000 to December
      2004 to ascertain the prevalence and antimicrobial susceptibility of Pseudomonas
      aeruginosa infections. Among 4709 positive isolates, 314 (6.67%) were Pseudomonas
      aeruginosa. The highest rate of infection due to Pseudomonas aeruginosa was
      observed in orthopedic ward (24.61%) and OPD (20%), in other wards the infection
      was between 13% to 1.5%. Gender-wise prevalence showed 61.78% male and 38.22%
      females were infected by Pseudomonas aeruginosa. The highest percentage of
      Pseudomonas aeruginosa isolates were observed in pus (57.64%) and urine (24.2%)
      samples. Maximum Pseudomonas aeruginosa isolates were found between March to
      August and the highest percentage 13.846% was observed in June. Using the disc
      diffusion method, the resistance patterns of 314 isolates against 14
      antimicrobial agents were determined. The highest resistance was observed against
      ampicillin (> or = 98.4%), ampicillin/sulbactam (85.3%), co-amoxiclave (83.8%)
      and ofloxacin (68.4%) and least resistance was observed against amikacin (24%).
      Similarly the MIC for ampicillin (4 to >2048 microg/ml), ampicillin/sulbactam (1
      to 2048 microg/ml) and co-amoxiclave (1 to >2048 microg/ml) against clinical
      isolates of Pseudomonas aeruginosa was also high. High resistance of Pseudomonas
      aeruginosa against various commonly used antibiotics showed the alarming
      situation. The control of drug resistant Pseudomonas aeruginosa required rational
      prescribing and proper use of antibiotics.

PMID- 18614432
TI  - Report: quantitative estimation of beta-sitosterol, lupeol, quercetin and
      quercetin glycosides from leaflets of Soymida febrifuga using HPTLC technique.
AB  - Soymida febrifuga (Meliaceae) dried leaflets (10 gm) were extracted with
      petroleum ether. Unsaponifiable matter quantitatively used for sample
      preparation, labeled as SF-U. Another 10 gm leaflet powder was extracted with
      methanol and quantitatively used for sample preparation labeled as SF-A. Sample
      and standard solution were dosage on three different plates and developed in its
      respective mobile phase plates were scanned using TLC scanner III and estimated
      using integration software CATs 4.05. Calculations for percentage were done
      considering standard and sample R(f), AUC and dilution factor. Estimation of beta
      Sitosterol, Lupeol, Quercetin, Quercetin-3-O-galactoside, Quercetin-3-O-xyloside
      and Quercetin-3-O-rutinoside were determined as 0.02146% w/w, 0.0377% w/w,
      0.4079% w/w, 0.6197% w/w, 2.974% w/w and 3.235% w/w respectively with the help of
      HPLC techniques.

PMID- 18614433
TI  - Aromatase and estrogens in man reproduction: a review and latest advances.
AB  - The mammalian testis is a complex organ which produces spermatozoa and
      synthesizes steroids. The transformation of androgens into estrogens is catalyzed
      by aromatase, an enzymatic complex encoded by a single copy-gene (cyp19) which
      contains 18 exons, 9 of them being translated. In man besides Leydig cells, we
      have demonstrated the existence of a biologically active aromatase in immature
      germ cells and in ejaculated spermatozoa. In addition the presence of estrogen
      receptors (ERalpha and ERss) in immature germ cells and in spermatozoa has been
      reported. Concerning aromatase, a 30% decrease of the amount of mRNA is observed
      in immotile compared to motile sperm fraction from the same sample. In
      asthenoteratozoospermic, teratozoospermic and asthenozoospermic patients, the
      aromatase gene expression is decreased respectively by 67%, 52% and 44%, when
      compared to normospermic controls. Statistical analyses between the sperm
      morphology and the aromatase/GAPDH ratio have revealed a high degree of
      correlation (r=-0.64) between that ratio and the percentage of abnormal
      spermatozoa (especially microcephaly). In men genetically deficient in aromatase
      diminutions of sperm number and motility have been published. Therefore besides
      gonadotrophins and testosterone, estrogens are likely playing a relevant role in
      spermiogenesis and human male gamete maturation.

PMID- 18614434
TI  - Detection of Chlamydia trachomatis and Mycoplasma hominis, genitalium and
      Ureaplasma urealyticum by polymerase chain reaction in patients with sterile
      pyuria.
AB  - PURPOSE: Chlamydia trachomatis and Mycoplasma hominis, Mycoplasma genitalium, and
      Ureaplasma urealyticum are associated with various diseases of the urogenital
      tract, but they are usually not detected by routine microbiological diagnosis. To
      determine the occurrence of Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma
      genitalium, and Ureaplasma urealyticum in patients with sterile pyuria.
      MATERIAL/METHODS: Sterile pyuria urine samples collected during the period from
      February 2006 to April 2007 were tested by polymerase chain reaction (PCR) for
      the presence of C. trachomatis, M. hominis, M. genitalium, and U. urealyticum
      using specific primers for each species. A total of 200 sterile pyuria samples
      selected from about 2400 urine samples attending the genitourinary clinic at Al
      Shifa hospital, Gaza, during the period February 2006 to April 2007 and were
      analyzed for routine urine examination and cultured on MacConkey agar, blood
      agar, and sabouraud agar to detect the presence of bacteria and Candida. The 200
      samples (96 male, 104 female; aged >or=18 years) containing more than 10
      leukocytes / HPF and negative for culture (showing no significant growth after 24
      hr) were tested by PCR for C. trachomatis and M. hominis, M. genitalium, and U.
      urealyticum. RESULTS: C. trachomatis was detected in 20 samples (10%), U.
      urealyticum in 10 samples (5%), M. hominis in 6 samples (3%) and M. genitalium in
      2 samples (1%). The difference in occurrence of C. trachomatis was statistically
      insignificant between males and females (P=0.509), but it was significant
      (P=0.008) for U. urealyticum. M. hominis was detected only in samples collected
      from female patients. On the other hand, M. genitalium was detected only in men.
      CONCLUSION: PCR testing of sterile pyuria showed a significant number of C.
      trachomatis, Mycoplasma, and Ureaplasma infections. Consequently, PCR is
      recommended for the detection of those microorganisms in the urine samples of
      sterile pyuria patients.

PMID- 18614435
TI  - Factors contributing to weight loss, nutrition-related concerns and advice
      received by adults undergoing cancer treatment.
AB  - PURPOSE: The opinions and perceptions of patients are crucial throughout the
      cancer treatment process, as treatment is more effective when patient concerns
      are addressed. The present study was designed to identify history of weight loss
      since initiation of cancer treatment, specific nutrition-related problems and
      concerns (including food aversions, factors contributing to poor food intake and
      perceived nutrition-related problems), nutrition advice received by cancer
      treatment patients, and relations between items studied and reported
      unintentional weight loss. MATERIAL AND METHODS: A 23-item survey was completed
      by a convenience sample of 79 patients from treatment centers at a community
      hospital and oncologist office, of which 66 were included in the final analysis.
      Descriptive statistics included means, standard error, 95% confidence intervals,
      and frequency distributions. ANOVA and Pearson chi2 were used to evaluate
      differences in responses by treatment type and relations between items studied
      and reported unintentional weight loss. Twenty-seven (41%) of the 66 (27 males,
      39 females) were receiving radiation, 20 (30%) chemotherapy, and 19 (29%) both.
      RESULTS: Unintentional weight loss occurred for 41% since initiation of treatment
      (13% deficit), 27% had food aversions, 52% reported factors contributing to poor
      food intake, 50% had nutrition-related problems since initiation of treatment,
      and 89% had received nutrition advice. The prevalence of unintentional weight
      loss was significantly greater among patients who reported having food aversions,
      factors that had contributed to poor food intake, or nutrition-related problems.
      CONCLUSIONS: This study demonstrates that adults commonly present with factors
      that contribute to poor food intake and perceive nutrition-related problems
      resulting from cancer treatment. Further, there is a greater prevalence of
      unintentional weight loss among those who report food aversions and perceive
      nutrition-related problems. The findings provide a framework that may aid
      healthcare providers in recognizing nutrition-related concerns and needs of
      cancer patients.

PMID- 18614436
TI  - The effect of granulocyte colony-stimulating factor (G-CSF) on the activity of
      granulocyte enzymes in children with cancer who developed neutropenia after
      chemotherapy.
AB  - PURPOSE: G-CSF is a cytokine that stimulates the proliferation and maturation of
      granulocyte precursor cells. The results of in vitro and in vivo investigations
      conducted on animal models revealed that this cytokine influences the functions
      of mature granulocytes increasing the activities of the granulocyte enzymes
      participating in phagocytosis. MATERIAL AND METHODS: The investigation was
      conducted on a group of 26 children (age: 1.5-17 years) with cancer who developed
      neutropenia after chemotherapy and were treated with G-CSF. The control group
      included 29 healthy children (age: 5-17 years). The heparinized blood samples
      were taken before the injection of the stimulator (time 0) and after the 2nd and
      5th injection of G-CSF (on day 3 and 6). Activities of granulocyte enzymes
      involved in the process of phagocytosis (myeloperoxidase, acid and alkaline
      phosphatase and esterase) in blood smears were evaluated. RESULTS: It has been
      found that G-CSF affects the activity of granulocyte enzymes by the normalization
      of decreased values of myeloperoxidase, acid phosphate and increasing the normal
      values of alkaline phosphate activity. The enzyme activities increased during the
      following days of treatment. CONCLUSION: Based on the obtained results, we can
      conclude that G-CSF activates the formation of fully competent granulocytes in
      cytostatic-treated children with various neoplastic diseases.

PMID- 18614437
TI  - Expression of MUC1 mucin in full-term pregnancy human placenta.
AB  - PURPOSE: MUC1 mucin is a component of glycocalyx in human endometrium and may
      play an important role in generation of "receptive window" at embryo
      implantation. Considering that MUC1 expression in human placenta is changed
      during pregnancy, and that MUC1 structure and function are not completely known
      in this organ, we have undertaken isolation of this mucin and detection of glycan
      epitopes, since they are crucial for its properties. MATERIAL AND METHODS:
      Samples of human placenta were homogenized and MUC1 was extracted in different
      conditions with the use of ionic or non-ionic detergents. Identification of this
      glycoprotein was performed by Western and lectin blotting, after its purification
      on Sepharose 4B column. RESULTS: The best extraction of MUC1 glycoprotein was
      achieved with a non-ionic detergent, Triton X-100. Reactions with anti-MUC1
      antibody showed a few glycoforms with molecular weights between 116 and 205 kDa,
      with the most visible glycoform approximating 205 kDa. Reactions with lectins
      enabled detection of carbohydrate antigens, such as T and Tn with sialic acid
      linked by alpha2, 3 and to a lesser extent by alpha2, 6 bond. CONCLUSION: MUC1
      mucin is present in several glycoforms on the maternal side of human placenta
      after term delivery. They contain short glycan structures, similar to some tumor
      carbohydrate antigens.

PMID- 18614438
TI  - Spontaneous rupture of splenic artery aneurysm in pregnancy: a case report.
AB  - Splenic artery aneurysms (SAA) occur predominantly in women, and the majority of
      them are asymptomatic until rupture. Over half of those that rupture occur during
      pregnancy. Spontaneously ruptured SAA during pregnancy is always a life
      threatening surgical entity for both the mother and the fetus. We report the case
      of a 29-year-old woman at 34 weeks' gestation with spontaneous rupture of SAA who
      underwent emergency exploratory laparotomy and splenectomy. This case illustrates
      the need to consider ruptured SAA as part of important differential diagnosis in
      haemodynamically unstable pregnant women.

PMID- 18614439
TI  - Fas expression in primary breast cancer is related to neoplastic infiltration of
      perilymphatic fat.
AB  - PURPOSE: Various studies have revealed that both Fas and its ligand play an
      important role in cancer biology. The aim of our study was to determine if there
      is a relationship between the expression of Fas or Fas-ligand in breast cancer
      and the presence of malignant cells in perilymphatic fat. MATERIAL/METHODS: Tumor
      samples from 147 consecutive breast cancer patients, aged 35-81 (median, 59),
      were subjected to analysis. The expressions of Fas and Fas-ligand were determined
      immunohistochemically. RESULTS: The expression of Fas, but not Fas-ligand, was
      significantly less frequent in breast cancer patients in whom malignant cells
      infiltrated through the perilymphatic fat (p=0.042). The infiltration of
      paranodal fatty tissue occurred more often in cases of ductal carcinomas
      (p=0.008), larger primary tumors (pT>or=2, p=0.030) and regional lymph node
      involvement (pN>or=1, p=0.021). Univariate analysis revealed that perilymphatic
      fat infiltration shortened overall survivals in breast cancer patients (p=0.05),
      similarly to postmenopausal status (p=0.034), age >60 years (p=0.05) and regional
      lymph node involvement (p=0.05). None of the aforementioned factors, however, was
      revealed as an independent predictor of survival in multivariate analysis.
      CONCLUSIONS: The study showed that lack of Fas in primary breast cancer is
      associated with perilymphatic fat infiltration. Consequently, both the absence of
      Fas in the primary tumor and the occurrence of neoplatic cells in paranodal fatty
      tissue should be considered in the prognosis, complementing existing conventional
      factors.

PMID- 18614440
TI  - BAL fluid cells and pulmonary function in different radiographic stages of newly
      diagnosed sarcoidosis.
AB  - PURPOSE: Sarcoidosis affected lungs detected in more than 90% of patients. The
      relationship between different stages of pulmonary sarcoidosis and pulmonary
      function tests (PFT) as well as bronchoalveolar lavage fluid (BALF) cells can be
      established. Geographic and ethnic factors are known to be linked to the specific
      characteristics of patients with sarcoidosis. The purpose of the study was to
      evaluate peculiarities of BALF cells pattern and pulmonary function tests at the
      time of the diagnosis of different radiographic types of sarcoidosis in a large
      group of Lithuanian sarcoid patients. MATERIAL AND METHODS: This is the
      prospective study of BALF cells and PFT of patients with newly diagnosed
      sarcoidosis. The study population consisted of 221 non-treated non-smoker
      patients. All patients underwent BAL and the majority of them underwent PFT.
      RESULTS: Comparing Stage I to Stage III groups, a slight increase in the
      macrophage and neutrophil count and a decrease of lymphocyte count was apparent.
      However, the leukocyte population difference was not statistically significant.
      We have observed significant increase of CD8 cell count, as well as a decrease of
      both the CD4 cell count and the CD4/CD8 ratio from Stage I to Stage III. We have
      determined statistically significant differences in all PFT parameters among the
      patient groups with different radiographic stages of sarcoidosis. The values of
      FVC, VC and TLC tended to decrease with an elevation of BALF neutrophils and/or
      eosinophils count. However BALF cells did not correlate well with PFT indices.
      CONCLUSIONS: In newly diagnosed sarcoid patients, BALF cell and PFT markers
      depend on the sarcoidosis stage.

PMID- 18614441
TI  - A case of Gianotti Crosti syndrome with HBV infection.
AB  - Gianotti-Crosti syndrome (papular acrodermatitis of childhood), which was first
      described in 1955, is a nonspecific rash that usually consists of the abrupt
      onset of pink flesh coloring, smooth or lichenoid, flat-topped papules. It was
      first related to hepatitis B virus (HBV) infection; however, cases not associated
      with HBV infection were reported as well. Although a type of delayed
      hypersensitivity reaction is speculated as a cause, exact pathogenesis still
      remains unclear. The prognosis is favorable and successful management relies upon
      general supportive and symptomatic care. We report a seven-year-old boy diagnosed
      with Gianotti-Crosti syndrome with monomorphous papules on his cheeks, buttocks
      and extremities associated with hepatitis B virus infection.

PMID- 18614442
TI  - Abnormalities in tooth morphology, structure and dentition in two children with
      chromosome aberrations. Translocation trisomy 13 and trisomy 21.
AB  - PURPOSE: Dental malformations due to chromosomal trisomies are rarely described
      and need an intensive cooperation between pediatricians, orthodonticians and
      human geneticists to enable the collection of data and to extend the
      investigations on specific parameters of the teeth. RESULTS: Here we present
      tooth studies of two children with trisomies 13 (Patau-syndrome) and 21 (Down
      syndrome): the dentition, the tooth morphology and the structure as well as the
      composition were investigated over a period of six years. Both male patients
      showed a delayed and abnormal dentition. Morphologic and structural changes
      compared to the general population were also detectable; whereas, the composition
      of the teeth was unchanged in enamel, dentin, and the border between them.
      CONCLUSIONS: The abnormalities in all parameters investigated were more
      pronounced in the patient with Patau-syndrome than in the child with Down
      syndrome.

PMID- 18614443
TI  - Significance of bronchoscopic lung biopsy in clinical practice.
AB  - PURPOSE: At present bronchoscopic lung biopsy (BLB) is widely used to diagnose
      various lung diseases. However placing of BLB in the diagnostic sequence of
      various clinical situations is not so clear. The purpose of the study was to
      evaluate the diagnostic value of BLB in a daily clinical practice. MATERIAL AND
      METHODS: The data obtained from the case records of all 304 patients who had
      undergone BLB since January 1996 to December 2007 at the Centre of Pulmonology
      and Allergology of Vilnius University Hospital Santariskiu klinikos (Vilnius,
      Lithuania) were examined. RESULTS: Most of indications for BLB were a peripheral
      lung nodule (40% of all the cases), dissemination in the lung (24% of all BLBs)
      and non-resolving pulmonary infiltrates (16.3% of all biopsies). Adequate lung
      tissue for histological examination was obtained in 85% of the cases. Based on
      the pathological diagnosis and findings of other diagnostic methods the final
      clinical diagnosis was verified for most of the patients. However, at least in 8%
      of the cases, the final clinical diagnosis was yet syndromic. Of all the BLBs,
      serious complications occurred in 8 (2.6%) patients. Clinically significant
      pneumothorax requiring chest tube treatment occurred in 5 (1.6%) of 304 patients.
      Severe bleeding occurred in 3 (1%) out of all BLBs. CONCLUSION: BLB is a
      relatively effective and safe method for diagnosing lung diseases. In most cases
      of the lung infiltrate, nodule, dissemination and diffuse changes, BLB is
      suitable to choose method for lung biopsy.

PMID- 18614444
TI  - The virtues of dissent and dialogue.

PMID- 18614445
TI  - Understanding how clinician-patient relationships and relational continuity of
      care affect recovery from serious mental illness: STARS study results.
AB  - OBJECTIVE: Recommendations for improving care include increased patient-clinician
      collaboration, patient empowerment, and greater relational continuity of care.
      All rely upon good clinician-patient relationships, yet little is known about how
      relational continuity and clinician-patient relationships interact, or their
      effects on recovery from mental illness. METHODS: Individuals (92 women, 85 men)
      with schizophrenia, schizoaffective disorder, affective psychosis, or bipolar
      disorder participated in this observational study. Participants completed in
      depth interviews detailing personal and mental health histories. Questionnaires
      included quality of life and recovery assessments and were linked to records of
      services used. Qualitative analyses yielded a hypothesized model of the effects
      of relational continuity and clinician-patient relationships on recovery and
      quality of life, tested using covariance structure modeling. RESULTS: Qualitative
      data showed that positive, trusting relationships with clinicians, developed over
      time, aid recovery. When "fit" with clinicians was good, long-term relational
      continuity of care allowed development of close, collaborative relationships,
      fostered good illness and medication management, and supported patient-directed
      decisions. Most valued were competent, caring, trustworthy, and trusting
      clinicians who treated clinical encounters "like friendships," increasing
      willingness to seek help and continue care when treatments were not effective and
      supporting "normal" rather than "mentally ill" identities. Statistical models
      showed positive relationships between recovery-oriented patient-driven care and
      satisfaction with clinicians, medication satisfaction, and recovery. Relational
      continuity indirectly affected quality of life via satisfaction with clinicians;
      medication satisfaction was associated with fewer symptoms; fewer symptoms were
      associated with recovery and better quality of life. CONCLUSIONS: Strong
      clinician-patient relationships, relational continuity, and a caring,
      collaborative approach facilitate recovery from mental illness and improved
      quality of life.

PMID- 18614446
TI  - Correlates of insider and outsider conceptualizations of recovery.
AB  - OBJECTIVE: The concept of recovery can be based on the self report of the
      individual experiencing the phenomenon ("insider" perspective) or objectively
      measured by clinicians and researchers ("outsider perspective"). The purpose of
      this study was to examine the relations among insider (hope and empowerment) and
      outsider (symptoms and cognition) variables of recovery. METHODS: 66 individuals
      with schizophrenia, bipolar disorder or major depression were administered the
      Brief Psychiatric Rating Scale, a battery of cognitive measures, The Hope Scale
      and The Empowerment Scale. RESULTS: For symptoms, depression and anxiety had the
      strongest relationships with hope and empowerment. Cognition was associated with
      a subset of activist oriented empowerment subscales. There were strong
      relationships among the hope and empowerment measures but few relationships among
      symptoms and cognition. CONCLUSIONS: Relationships exist between insider and
      outsider conceptualizations of recovery in that symptoms and cognition are
      associated with some aspects of hope and empowerment.

PMID- 18614447
TI  - Building life around foster home versus moving on: the competing needs of people
      living in foster homes.
AB  - OBJECTIVE: This article reports findings on the competing needs of people living
      in psychiatric foster homes in Montreal, Canada. METHODS: Semi-structured
      interviews were conducted with 33 residents. Consumers describe the tensions
      associated with foster home life. RESULTS: Two overall competing needs emerged:
      the need to build their lives around the foster home and the need to build life
      beyond the foster home. Residents describe their need for security and support
      versus their need for greater personal autonomy, the dilemmas associated with
      communal living, and their struggle to envisage a positive future. CONCLUSIONS:
      These findings have important implications for mental health professionals
      mandated to dismantle foster homes for more autonomous housing.

PMID- 18614448
TI  - A two-year longitudinal study of the Kansas consumers as providers training
      program.
AB  - OBJECTIVE: This study reports student outcomes for the Kansas Consumers as
      Providers (CAP) training program. Graduates provide mental health services to
      other consumers in the community. CAP is a semester-long class plus a 104-hour
      internship in a social service agency. METHODS: This paper reports on the results
      of a two-year quantitative, longitudinal study of people with psychiatric
      disabilities who completed the program. RESULTS: Graduates had statistically
      significant pre-post differences in employment and post-secondary education
      enrollment at all three follow-up points. CONCLUSION: Results suggest that CAP
      graduates can and do provide valuable mental health services to other consumers.

PMID- 18614449
TI  - The work and recovery project: changing organizational culture and practice in
      New York City outpatient services.
AB  - TOPIC: Complex and multiple barriers confront out-patient programs in promoting
      recovery and addressing mental health recipients' work-related goals. This
      article describes a focused organizational change project utilizing intensive
      consultation and technical assistance within five New York City outpatient
      psychiatric services. PURPOSE: The project aimed to increase staff exposure to,
      understanding and use of work-related and recovery-based concepts to promote
      consumers' recovery and attainment of employment goals. SOURCES USED: Tailored
      assessment, curriculum delivery, and identification and implementation of change
      objectives were useful strategies in promoting change. CONCLUSIONS: This change
      model can serve to assist programs in their efforts to integrate new approaches
      and to better understand changes among leadership, staff and consumers, and
      changes in organizational culture and practice required to support a work and
      recovery-oriented service paradigm. The project experience suggests that adopting
      and embracing new practices takes time. Varied and incremental steps toward
      programmatic and operational changes can be significant and can reap authentic
      sustainable change occurring in the process of learning, experiencing,
      internalizing and adjusting to new methods of practice.

PMID- 18614450
TI  - Participant evaluation of a CBT program for enhancing work function in
      schizophrenia.
AB  - OBJECTIVES: While much has been written about the benefits of CBT for persons
      with schizophrenia, little has been published to date exploring participant
      evaluations of these programs. This paper reports on participant evaluations of
      such a program. METHODS: Forty-four participants with schizophrenia or
      schizoaffective disorder were surveyed regarding their satisfaction with a 6
      month weekly group and individual CBT intervention developed as an adjunct to
      work therapy or the control condition support group during a randomized
      controlled feasibility study. RESULTS: Results suggest that all participants,
      those receiving the CBT intervention and the support group, were satisfied with
      their program, on average rating the program between "good" and "excellent."
      However, in comparison, the CBT intervention was associated with greater
      participant satisfaction than support alone, particularly the perception of the
      overall quality of services and assistance with problem-solving. CONCLUSIONS: It
      appears that participant evaluations can function as a source of useful data for
      evaluation of CBT interventions for persons who have schizophrenia. However,
      further study is needed to more fully identify and understand aspects of CBT that
      participants with schizophrenia evaluate as particularly positive or negative and
      to explore acceptable trade-offs among them.

PMID- 18614452
TI  - The challenge of integrating employment services with public mental health
      services in Australia: progress at the first demonstration site.
AB  - OBJECTIVE: Integrating vocational services into public mental health services is
      a key component of evidence-based supported employment for people with severe
      mental illness. While this approach has been developed in the USA, it has only
      recently been attempted internationally and in Australia. This report summarizes
      the early implementation challenges at the first Australian demonstration site.
      METHOD: ORYGEN Youth Health (OYH) in Melbourne established an evidence-based
      supported employment research project in December 2005. Challenges to service
      integration and fidelity were documented descriptively in order to inform other
      international sites attempting to implement similar evidence-based practices.
      RESULTS: Experiences at this demonstration site identify the major barriers to
      integration and suggest how these can be overcome. CONCLUSION: Successful
      integration of employment with youth mental health services is feasible in
      Australia within six months.

PMID- 18614451
TI  - The meaning and importance of employment to people in recovery from serious
      mental illness: results of a qualitative study.
AB  - OBJECTIVE: Given the high rates of unemployment and underemployment among
      individuals with psychiatric disabilities, only a small number of studies have
      investigated the role work has in the lives of people who have been successful
      vocationally during their recovery from serious mental illness. This study sought
      to add to existing literature by determining how individuals perceive work and
      its effect on their recovery. METHODS: We purposefully recruited self-referred
      participants at moderate to advanced levels of recovery and qualitatively
      analyzed semi-structured interviews conducted with 23 individuals to identify
      themes related to work in the context of recovery from serious mental illness.
      RESULTS: Participants described myriad positive benefits associated with paid
      employment, which conceptually fell across two main domains: work has personal
      meaning and work promotes recovery. Participants discussed the ways in which work
      fostered pride and self-esteem, offered financial benefits, provided coping
      strategies for psychiatric symptoms, and ultimately facilitated the process of
      recovery. Participants also discussed the importance and benefits associated with
      working in a helper-role and as consumer providers. CONCLUSIONS: Overall,
      individuals reported that employment conferred significant benefits in their
      process of recovery from mental illness and that work played a central role in
      their lives and identities. The themes from this study should be considered when
      developing employment or other recovery-oriented programs for people with serious
      mental illness.

PMID- 18614453
TI  - The educational goals of people with psychiatric disabilities.
AB  - OBJECTIVE: Many people with psychiatric disability have educational goals. In
      this paper, we survey a sample to describe the frequency of academic interests,
      specific goals related to this interest, and barriers that undermine education.
      METHODS: One hundred and four people from a large Midwestern mental health center
      completed the Educational Goals Survey (EGS) which was developed with feedback
      from two consumer focus groups. RESULTS: Almost two thirds of respondents never
      got beyond high school education. Of this group, 54.5% wanted to go back to
      school. Reasons for returning to school included improving one's job status and
      enhancing personal growth. CONCLUSIONS: Two sets of barriers emerged from the
      data; those which are consistent with any adult student and those which must be
      addressed because of disability. We make sense of these data by comparing results
      with the U.S. Census where appropriate.

PMID- 18614454
TI  - Student supervision from a PSR perspective.

PMID- 18614457
TI  - IL-18 levels in nasal lavage after inhalatory challenge test with flour in bakers
      diagnosed with occupational asthma.
AB  - OBJECTIVES: The authors discuss the outcomes of a study on IL-18 concentration in
      nasal washings after the inhalatory challenge test with flour allergens (ICHT-F)
      in bakers with flour-induced occupational airway allergy (OAA). METHODS: We
      measured IL-18 concentration using ELISA kit and assessed morphological changes
      in nasal lavage fluid (NLF) before, and 4 h and 24 h after ICHT-F in three groups
      of subjects: Group A - 9 patients with diagnosed OAA (occupational asthma and
      rhinitis), Group B - 10 patients with atopic asthma and rhinitis, and Group C - 9
      healthy volunteers. RESULTS: In Group A, significant differences in the basophil
      proportion in NLF were noted only 24 h after ICHT-F. Both the basophil proportion
      and total eosinophil count were higher in Group A than in Group C at this time
      point. Group A also showed a statistically significant increase in IL-18 levels 4
      h after the challenge. A significant relationship was noted between the
      proportion of basophils 4 h after ICHT-F and IL-18 level at 24 h after the test.
      CONCLUSIONS: This is the first study demonstrating an increased expression of IL
      18 in nasal washings of subjects diagnosed with OAA to flour allergens. The
      observed higher concentrations of IL-18 in nasal washings after ICHT as well as
      the increase in the proportion of basophils provide evidence for the important
      role of IL-18 in persistent allergic inflammation.

PMID- 18614459
TI  - Prenatal and childhood exposure to pesticides and neurobehavioral development:
      review of epidemiological studies.
AB  - OBJECTIVES: Conventional pesticides comprise a diverse group of substances
      intended to destroy, repel or control organisms identified as pests. Compared to
      the studies on lead, mercury, and PCBs, few epidemiological studies have assessed
      the developmental neurotoxicity of pesticides. MATERIALS AND METHODS:
      Epidemiological studies focused on the neurobehavioural development of children
      exposed to pesticides were identified by searching the PubMed, Medline, EBSCO,
      Agricola and TOXNET databases. RESULTS: The findings of the studies reviewed
      imply that children's exposure to pesticides may bring about impairments in their
      neurobehavioral development. Children exposed to organophosphate pesticides (OP),
      both prenatally and during childhood, may have difficulties performing tasks that
      involve short-term memory, and may show increased reaction time, impaired mental
      development or pervasive developmental problems. In newborns, the effects of OP
      exposure are manifested mainly by an increased number of abnormal reflexes, while
      in adolescents, by mental and emotional problems. The studies investigating
      association between exposure to organochlorine pesticides and neurodevelopmental
      effects show inconsistent results. While some studies report impairments in
      mental and psychomotor functions, other studies do not confirm the above.
      CONCLUSION: The information deriving from epidemiological studies indicate a need
      to increase awareness among people and children exposed to pesticides about the
      association between the use of pesticides and neurodevelopmental impairments.
      Therefore, the principle of prudence should become a rule.

PMID- 18614461
TI  - The problem in setting research priorities: a layman's experience.

PMID- 18614463
TI  - Giant cell arteritis causing aortic dissection and acute hypertension.

PMID- 18614460
TI  - Occupational exposures and risk of oesophageal cancer by histological type: a
      case-control study in eastern Spain.
AB  - OBJECTIVE: To explore the relationship between occupations and specific
      occupational exposures and oesophageal cancer (OC) by histological type. METHODS:
      A multicentre hospital-based case-control study was conducted in two
      Mediterranean provinces of Spain. Occupational, sociodemographic and lifestyle
      information was collected from 185 newly diagnosed male oesophageal cancer
      patients (147 squamous cell, 38 adenocarcinoma) and 285 frequency matched
      controls. Occupation was coded according to the Spanish National Classification
      of Occupations 1994. Occupational exposure to a selection of carcinogenic
      substances was assessed by the FINJEM job exposure matrix. Odds ratios were
      calculated by unconditional logistic regression adjusting for age, education,
      alcohol intake and cigarette smoking. RESULTS: For the squamous cell variety,
      statistically significant associations were found for waiters and bartenders (OR
      8.18, 95% CI 1.98 to 33.75) and miners, shotfirers, stone cutters and carvers (OR
      10.78, 95% CI 1.24 to 93.7) in relation to other occupations. For the
      adenocarcinoma variety, statistically significant associations were observed for
      carpenters and joiners (OR 9.69), animal producers and related workers (OR 5.61)
      and building and related electricians (OR 8.26), although these observations were
      based on a low number of cases. Regarding specific exposures, the study found a
      statistically significant increased risk of squamous cell carcinoma for ionising
      radiation, and of adenocarcinoma for high exposure to volatile sulphur compounds
      (OR 3.12) and lead (OR 5.30). For all histological types of OC combined, a three
      fold increase in risk was found with a significant trend for asbestos exposure
      (OR 3.46, 95% CI 0.99 to 12.10). CONCLUSIONS: The data suggest that some
      occupational exposures may specifically increase the risk of oesophageal squamous
      cell carcinoma or adenocarcinoma, while other exposures such as asbestos may
      increase the overall risk of OC.

PMID- 18614462
TI  - Management of breast cancer--part I.

PMID- 18614466
TI  - Globalisation of anti-doping: the reverse side of the medal.

PMID- 18614468
TI  - Anyone for club med?

PMID- 18614469
TI  - GMC calls for greater safeguards when doctors and patients move across EU
      borders.

PMID- 18614472
TI  - Lords committee comes down against presumed consent for organ donation.

PMID- 18614473
TI  - Prognosis in patients with recent onset low back pain in Australian primary care:
      inception cohort study.
AB  - OBJECTIVE: To estimate the one year prognosis and identify prognostic factors in
      cases of recent onset low back pain managed in primary care. DESIGN: Cohort study
      with one year follow-up. SETTING: Primary care clinics in Sydney, Australia.
      PARTICIPANTS: An inception cohort of 973 consecutive primary care patients (mean
      age 43.3, 54.8% men) with non-specific low back pain of less than two weeks'
      duration recruited from the clinics of 170 general practitioners,
      physiotherapists, and chiropractors. MAIN OUTCOME MEASURES: Participants
      completed a baseline questionnaire and were contacted six weeks, three months,
      and 12 months after the initial consultation. Recovery was assessed in terms of
      return to work, return to function, and resolution of pain. The association
      between potential prognostic factors and time to recovery was modelled with Cox
      regression. RESULTS: The follow-up rate over the 12 months was more than 97%.
      Half of those who reduced their work status at baseline had returned to previous
      work status within 14 days (95% confidence interval 11 to 17 days) and 83% had
      returned to previous work status by three months. Disability (median recovery
      time 31 days, 25 to 37 days) and pain (median 58 days, 52 to 63 days) took much
      longer to resolve. Only 72% of participants had completely recovered 12 months
      after the baseline consultation. Older age, compensation cases, higher pain
      intensity, longer duration of low back pain before consultation, more days of
      reduced activity because of lower back pain before consultation, feelings of
      depression, and a perceived risk of persistence were each associated with a
      longer time to recovery. CONCLUSIONS: In this cohort of patients with acute low
      back pain in primary care, prognosis was not as favourable as claimed in clinical
      practice guidelines. Recovery was slow for most patients. Nearly a third of
      patients did not recover from the presenting episode within a year.

PMID- 18614474
TI  - Genetic engineering in athletes.

PMID- 18614475
TI  - New contract pushes up cost of GP care in Scotland.

PMID- 18614477
TI  - Junior doctors' desire to practise falls in first year of training.

PMID- 18614478
TI  - Southall cleared of conducting trial without parents' consent.

PMID- 18614479
TI  - BMA calls for ban on smoking images that "keep the habit cool" among children.

PMID- 18614482
TI  - Routine care of peripheral intravenous catheters versus clinically indicated
      replacement: randomised controlled trial.
AB  - OBJECTIVE: To compare routine replacement of intravenous peripheral catheters
      with replacement only when clinically indicated. DESIGN: Randomised controlled
      trial. SETTING: Tertiary hospital in Australia. PARTICIPANTS: 755 medical and
      surgical patients: 379 allocated to catheter replacement only when clinically
      indicated and 376 allocated to routine care of catheter (control group). MAIN
      OUTCOME MEASURE: A composite measure of catheter failure resulting from phlebitis
      or infiltration. RESULTS: Catheters were removed because of phlebitis or
      infiltration from 123 of 376 (33%) patients in the control group compared with
      143 of 379 (38%) patients in the intervention group; the difference was not
      significant (relative risk 1.15, 95% confidence interval 0.95 to 1.40). When the
      analysis was based on failure per 1000 device days (number of failures divided by
      number of days catheterised, divided by 1000), no difference could be detected
      between the groups (relative risk 0.98, 0.78 to 1.24). Infusion related costs
      were higher in the control group (mean $A41.02; pound19.71; euro24.80; $38.55)
      than intervention group ($A36.40). The rate of phlebitis in both groups was low
      (4% in intervention group, 3% in control group). CONCLUSION: Replacing peripheral
      intravenous catheters when clinically indicated has no effect on the incidence of
      failure, based on a composite measure of phlebitis or infiltration. Larger trials
      are needed to test this finding using phlebitis alone as a more clinically
      meaningful outcome. REGISTRATION NUMBER: Australian New Zealand Clinical Trials
      Registry ACTRN12605000147684.

PMID- 18614483
TI  - Improving the safety of peripheral intravenous catheters.

PMID- 18614485
TI  - UN warns of millions at risk of starvation in drought stricken Ethiopia, Somalia,
      and Afghanistan.

PMID- 18614486
TI  - US doctors display "No drug reps" signs.

PMID- 18614488
TI  - Enhancing the quality and transparency of health research.

PMID- 18614489
TI  - German watchdog investigates drug company's online education courses.

PMID- 18614490
TI  - Double standards in obtaining consent for piercings.

PMID- 18614491
TI  - Health and regulation issues for body piercing.

PMID- 18614492
TI  - Role of alpha agonists in treating anaphylaxis.

PMID- 18614493
TI  - Attitudes to NICE guidance on refeeding syndrome.

PMID- 18614494
TI  - Virtual congress of general practice is thriving.

PMID- 18614495
TI  - Surgeons have held conferences in Second Life.

PMID- 18614496
TI  - National cancer director responds on top-up payments.

PMID- 18614497
TI  - Pfizer stops funding medical education provided by profit making companies.

PMID- 18614498
TI  - Project seeks to improve dancers' health.

PMID- 18614502
TI  - NICE recommendations have had little effect on multiple sclerosis services five
      years on.

PMID- 18614503
TI  - Psychiatric patients less violent when smoking restricted.

PMID- 18614504
TI  - Sexuality and older people.

PMID- 18614505
TI  - Secular trends in self reported sexual activity and satisfaction in Swedish 70
      year olds: cross sectional survey of four populations, 1971-2001.
AB  - OBJECTIVE: To study secular trends in self reported sexual behaviour among 70
      year olds. DESIGN: Cross sectional survey. Settings Four samples representative
      of the general population in Gothenburg, Sweden. PARTICIPANTS: 1506 adults (946
      women, 560 men) examined in 1971-2, 1976-7, 1992-3, and 2000-1. MAIN OUTCOME
      MEASURES: Sexual intercourse, attitudes to sexuality in later life, sexual
      dysfunctions, and marital satisfaction. RESULTS: From 1971 to 2000 the proportion
      of 70 year olds reporting sexual intercourse increased among all groups: married
      men from 52% to 68% (P=0.002), married women from 38% to 56% (P=0.001), unmarried
      men from 30% to 54% (P=0.016), and unmarried women from 0.8% to 12% (P<0.001).
      Men and women from later birth cohorts reported higher satisfaction with
      sexuality, fewer sexual dysfunctions, and more positive attitudes to sexuality in
      later life than those from earlier birth cohorts. A larger proportion of men (57%
      v 40%, P<0.001) and women (52% v 35%, P<0.001) reported very happy relationships
      in 2000-1 compared with those in 1971-2. Sexual debut before age 20 increased in
      both sexes: in men from 52% to 77% (P<0.001) and in women from 19% to 64%
      (P<0.001). CONCLUSION: Self reported quantity and quality of sexual experiences
      among Swedish 70 year olds has improved over a 30 year period.

PMID- 18614506
TI  - New model of health promotion and disease prevention for the 21st century.

PMID- 18614507
TI  - Has the time come to take on time itself?

PMID- 18614508
TI  - Should disadvantaged people be paid to take care of their health? Yes.

PMID- 18614509
TI  - Should disadvantaged people be paid to take care of their health? No.

PMID- 18614510
TI  - New York's road to health.

PMID- 18614511
TI  - Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK:
      population based cohort study.
AB  - OBJECTIVE: To determine the incidence of and mortality from bullous pemphigoid
      and pemphigus vulgaris in the United Kingdom. DESIGN: Retrospective historical
      cohort study. SETTING: Computerised medical records from the health improvement
      network, a large population based UK general practice database. PARTICIPANTS:
      Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age,
      sex, and practice matched controls. MAIN OUTCOME MEASURES: Incidence and
      mortality compared with the control population by calendar period, age group,
      sex, geographical region, and degree of social deprivation. RESULTS: 869 people
      with bullous pemphigoid and 138 people with pemphigus vulgaris were identified.
      The median age at presentation for bullous pemphigoid was 80 (range 23-102)
      years, and 534 (61%) patients were female. The median age at presentation for
      pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female.
      Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence
      interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence
      of bullous pemphigoid increased over time; the average yearly increase was 17%
      (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly
      increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0
      to 1.2) occurred. The risk of death for patients with bullous pemphigoid was
      twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence
      interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times
      greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2). CONCLUSIONS:
      Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The
      reasons for the changes in incidence are not clearly understood but have
      implications for identifying causative factors. Both disorders are associated
      with a high risk of death. Previous estimates may have underestimated the risk of
      death associated with these diseases.

PMID- 18614512
TI  - Incidence of bullous pemphigoid and pemphigus vulgaris.

PMID- 18614514
TI  - Internet crawler uses unconventional information sources to track infectious
      disease outbreaks.

PMID- 18614517
TI  - Antipsychotics for people with dementia.

PMID- 18614519
TI  - Investigating painless haematuria.

PMID- 18614520
TI  - Social determinants of health and the design of health programmes for the poor.

PMID- 18614521
TI  - Prophylaxis with co-trimoxazole for HIV infected adults in Africa.

PMID- 18614522
TI  - Left atrial linear lesions are required for successful treatment of persistent
      atrial fibrillation.
AB  - AIMS: This study evaluates the clinical outcome and incidence of left atrial (LA)
      macro re-entrant atrial tachycardia (AT) in patients in whom persistent atrial
      fibrillation (AF) terminated during catheter ablation without the need of roof
      and mitral lines. METHODS AND RESULTS: Persistent AF was terminated by ablation
      in 154 of 180 consecutive patients. AF history was 60 months including 11 months
      of continuous AF. Patients were divided into two groups: those who had not
      required both LA linear lesions to terminate AF (group A, 85 patients), and those
      who had (group B, 69 patients). There was no difference in clinical and
      echocardiographic characteristics between both groups except for a shorter
      duration of continuous AF in group A (9 vs.12 months, respectively) (P = 0.03).
      After 28 months of follow-up, the incidence of LA macro re-entrant AT
      necessitating linear ablation was higher in group A (76%) compared with group B
      (33%) (P = 0.002). When complete linear block could not be achieved during the
      index procedure, the incidence of subsequent roof (P = 0.008) or mitral isthmus
      (P = 0.010) dependent macro re-entrant AT was higher. CONCLUSION: Although
      persistent AF can be terminated by catheter ablation without linear lesions, the
      majority will require linear lesions for macro re-entrant AT.

PMID- 18614523
TI  - Plasma tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9:
      novel indicators of left ventricular remodelling and prognosis after acute
      myocardial infarction.
AB  - AIMS: Matrix metalloproteinase (MMP) activity is central to the development of
      left ventricular (LV) remodelling and dysfunction after acute myocardial
      infarction (AMI). We assessed the relationships with LV structure and function
      and outcome, of tissue inhibitors of metalloproteinase-1 (TIMP-1) and MMP-9, and
      compared with N-terminal pro-B-type natriuretic peptide (NTproBNP). METHODS AND
      RESULTS: We studied 404 patients with AMI. Primary outcome measures were the
      associations of TIMP-1, MMP-9, and NTproBNP with death or heart failure, and with
      LV dimensions, function and remodelling (DeltaLVEDV, change in LV end-diastolic
      volume between discharge and follow-up). Cut-off concentrations for prediction of
      death or heart failure were identified from receiver operator characteristic
      (ROC) curves. In multivariable analysis, TIMP-1 and NTproBNP had predictive value
      for LV ejection fraction pre-discharge (TIMP-1 P = 0.023; N-BNP P = 0.007) and at
      follow-up (TIMP-1 P = 0.001; N-BNP P = 0.003). MMP-9, TIMP-1, and NTproBNP
      correlated directly with LV volumes. MMP-9 (P = 0.005) and TIMP-1 (P = 0.036),
      but not NTproBNP, correlated with DeltaLVEDV. For the combined endpoint of death
      or heart failure the area under the ROC curve was 0.640 for MMP-9, 0.799 for
      NTproBNP and 0.811 for TIMP-1. Patients with TIMP-1 > 135 ng/mL (P < 0.001) or
      NTproBNP >1472 fmol/mL (P < 0.001) had increased risk of endpoint. Consideration
      of both NTproBNP and TIMP-1 further improved risk stratification. CONCLUSION:
      TIMP-1 and MMP-9 correlate with echocardiographic parameters of LV dysfunction
      and remodelling after AMI and may identify patients at risk of subsequent LV
      remodelling and adverse prognosis.

PMID- 18614524
TI  - Analysis of tetracycline resistance tet(W) genes and their flanking sequences in
      intestinal Bifidobacterium species.
AB  - OBJECTIVES: The tet(W) gene provides tetracycline resistance to a wide range of
      anaerobic intestinal and ruminal bacteria, but little is known about the
      molecular organization of the tet(W) gene. The aim of this study was to gain new
      insights into the molecular organization of the tet(W) gene in bifidobacteria
      strains from humans. METHODS: A segment of DNA encompassing the whole tet(W) gene
      and its immediate upstream and downstream sequences was analysed in 10
      representative strains of four Bifidobacterium species, of which two have been
      shown to be tetracycline-susceptible. The non-conserved flanking regions of the
      tet(W) gene were further analysed in six strains. RESULTS: All 10 strains share a
      core DNA domain of 2154 bp [starting 250 bp upstream of the tet(W) gene start
      codon and ending 13 bp before the stop codon] with 98% to 100% DNA identity.
      Except for Bifidobacterium animalis E43, all other strains further share 408 bp
      upstream and 70 bp downstream of the tet(W) gene. An insertion-like element of
      736 bp was found to interrupt the tet(W) coding sequence in Bifidobacterium
      longum M21, which may be the reason for its tetracycline susceptibility. However,
      genetic events explaining the susceptible phenotype of B. longum LMG 13197(T)
      were not observed. CONCLUSIONS: The tet(W) genes from all 10 strains shared 98%
      to 100% DNA and amino acid identity, though large variation was found in their
      flanking regions.

PMID- 18614525
TI  - Halogenase genes in nonribosomal peptide synthetase gene clusters of Microcystis
      (cyanobacteria): sporadic distribution and evolution.
AB  - Cyanobacteria of the genus Microcystis are known to produce secondary metabolites
      of large structural diversity by nonribosomal peptide synthetase (NRPS) pathways.
      For a number of such compounds, halogenated congeners have been reported along
      with nonhalogenated ones. In the present study, chlorinated cyanopeptolin- and/or
      aeruginosin-type peptides were detected by mass spectrometry in 17 out of 28
      axenic strains of Microcystis. In these strains, a halogenase gene was identified
      between 2 genes coding for NRPS modules in respective gene clusters, whereas it
      was consistently absent when the strains produced only nonchlorinated
      corresponding congeners. Nucleotide sequences were obtained for 12 complete
      halogenase genes and 14 intermodule regions of gene clusters lacking a halogenase
      gene or containing only fragments of it. When a halogenase gene was found absent,
      a specific, identical excision pattern was observed for both synthetase gene
      clusters in most strains. A phylogenetic analysis including other bacterial
      halogenases showed that the NRPS-related halogenases of Microcystis form a
      monophyletic group divided into 2 subgroups, corresponding to either the
      cyanopeptolin or the aeruginosin peptide synthetases. The distribution of these
      peptide synthetase gene clusters, among the tested Microcystis strains, was found
      in relative agreement with their phylogeny reconstructed from 16S-23S rDNA
      intergenic spacer sequences, whereas the distribution of the associated
      halogenase genes appears to be sporadic. The presented data suggest that in
      cyanobacteria these prevalent halogenase genes originated from an ancient
      horizontal gene transfer followed by duplication in the cyanobacterial lineage.
      We propose an evolutionary scenario implying repeated gene losses to explain the
      distribution of halogenase genes in 2 NRPS gene clusters that subsequently
      defines the seemingly erratic production of halogenated and nonhalogenated
      aeruginosins and cyanopeptolins among Microcystis strains.

PMID- 18614526
TI  - The complete nucleotide sequences of the 5 genetically distinct plastid genomes
      of Oenothera, subsection Oenothera: II. A microevolutionary view using
      bioinformatics and formal genetic data.
AB  - A unique combination of genetic features and a rich stock of information make the
      flowering plant genus Oenothera an appealing model to explore the molecular basis
      of speciation processes including nucleus-organelle coevolution. From
      representative species, we have recently reported complete nucleotide sequences
      of the 5 basic and genetically distinguishable plastid chromosomes of subsection
      Oenothera (I-V). In nature, Oenothera plastid genomes are associated with 6
      distinct, either homozygous or heterozygous, diploid nuclear genotypes of the 3
      basic genomes A, B, or C. Artificially produced plastome-genome combinations that
      do not occur naturally often display interspecific plastome-genome
      incompatibility (PGI). In this study, we compare formal genetic data available
      from all 30 plastome-genome combinations with sequence differences between the
      plastomes to uncover potential determinants for interspecific PGI. Consistent
      with an active role in speciation, a remarkable number of genes have high Ka/Ks
      ratios. Different from the Solanacean cybrid model Atropa/tobacco, RNA editing
      seems not to be relevant for PGIs in Oenothera. However, predominantly sequence
      polymorphisms in intergenic segments are proposed as possible sources for PGI. A
      single locus, the bidirectional promoter region between psbB and clpP, is
      suggested to contribute to compartmental PGI in the interspecific AB hybrid
      containing plastome I (AB-I), consistent with its perturbed photosystem II
      activity.

PMID- 18614527
TI  - Phylogenetic analysis of nitrite, nitric oxide, and nitrous oxide respiratory
      enzymes reveal a complex evolutionary history for denitrification.
AB  - Denitrification is a facultative respiratory pathway in which nitrite (NO2(-)),
      nitric oxide (NO), and nitrous oxide (N2O) are successively reduced to nitrogen
      gas (N(2)), effectively closing the nitrogen cycle. The ability to denitrify is
      widely dispersed among prokaryotes, and this polyphyletic distribution has raised
      the possibility of horizontal gene transfer (HGT) having a substantial role in
      the evolution of denitrification. Comparisons of 16S rRNA and denitrification
      gene phylogenies in recent studies support this possibility; however, these
      results remain speculative as they are based on visual comparisons of phylogenies
      from partial sequences. We reanalyzed publicly available nirS, nirK, norB, and
      nosZ partial sequences using Bayesian and maximum likelihood phylogenetic
      inference. Concomitant analysis of denitrification genes with 16S rRNA sequences
      from the same organisms showed substantial differences between the trees, which
      were supported by examining the posterior probability of monophyletic constraints
      at different taxonomic levels. Although these differences suggest HGT of
      denitrification genes, the presence of structural variants for nirK, norB, and
      nosZ makes it difficult to determine HGT from other evolutionary events.
      Additional analysis using phylogenetic networks and likelihood ratio tests of
      phylogenies based on full-length sequences retrieved from genomes also revealed
      significant differences in tree topologies among denitrification and 16S rRNA
      gene phylogenies, with the exception of the nosZ gene phylogeny within the data
      set of the nirK-harboring genomes. However, inspection of codon usage and G + C
      content plots from complete genomes gave no evidence for recent HGT. Instead, the
      close proximity of denitrification gene copies in the genomes of several
      denitrifying bacteria suggests duplication. Although HGT cannot be ruled out as a
      factor in the evolution of denitrification genes, our analysis suggests that
      other phenomena, such gene duplication/divergence and lineage sorting, may have
      differently influenced the evolution of each denitrification gene.

PMID- 18614528
TI  - Structural and functional analysis of the human HDAC4 catalytic domain reveals a
      regulatory structural zinc-binding domain.
AB  - Histone deacetylases (HDACs) regulate chromatin status and gene expression, and
      their inhibition is of significant therapeutic interest. To date, no biological
      substrate for class IIa HDACs has been identified, and only low activity on
      acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and
      inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd)
      and of an HDAC4cd active site mutant with enhanced enzymatic activity toward
      acetylated lysines. The structures presented, coupled with activity data, provide
      the molecular basis for the intrinsically low enzymatic activity of class IIa
      HDACs toward acetylated lysines and reveal active site features that may guide
      the design of class-specific inhibitors. In addition, these structures reveal a
      conformationally flexible structural zinc-binding domain conserved in all class
      IIa enzymes. Importantly, either the mutation of residues coordinating the
      structural zinc ion or the binding of a class IIa selective inhibitor prevented
      the association of HDAC4 with the N-CoR.HDAC3 repressor complex. Together, these
      data suggest a key role of the structural zinc-binding domain in the regulation
      of class IIa HDAC functions.

PMID- 18614529
TI  - 15-deoxy-Delta12,14-prostaglandin J2 impairs phosphatidylcholine synthesis and
      induces nuclear accumulation of thiol-modified cytidylyltransferase.
AB  - Synthesis of phosphatidylcholine, the major phospholipid of animal cell
      membranes, requires the key enzyme cytidylyltransferase (CCTalpha). Cysteine
      sulfhydryls within CCTalpha are needed for full catalytic activity. Here we show
      that prostaglandin 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) inactivates CCTalpha by
      inducing generation of reactive oxidant species and the appearance of a cross
      linked CCTalpha dimer in cells. N-Acetyl-l-cysteine reduced oxidative stress,
      prevented CCTalpha cross-linking, and restored CCT function in 15d-PGJ2-treated
      cells. 15d-PGJ2 modified critical cysteine residues within CCTalpha as determined
      by mutagenesis studies and by incorporation of biotin-15d-PGJ2 into CCTalpha.
      These effects of 15d-PGJ2 were associated with CCTalpha accumulation within the
      nucleus. The data indicate that bioactive prostanoids significantly impair
      membrane phospholipid production by promoting cysteine cross-bridging within
      CCTalpha.

PMID- 18614530
TI  - Mutational analysis of the helicase-like domain of Thermotoga maritima reverse
      gyrase.
AB  - Reverse gyrase is a unique type IA topoisomerase that is able to introduce
      positive supercoils into DNA in an ATP-dependent process. ATP is bound to the
      helicase-like domain of the enzyme that contains most of the conserved motifs
      found in helicases of the SF1 and SF2 superfamilies. In this paper, we have
      investigated the role of the conserved helicase motifs I, II, V, VI, and Q by
      generating mutants of the Thermotoga maritima reverse gyrase. We show that
      mutations in motifs I, II, V, and VI completely eliminate the supercoiling
      activity of reverse gyrase and that a mutation in the Q motif significantly
      reduces this activity. Further analysis revealed that for most mutants, the DNA
      binding and cleavage properties are not significantly changed compared with the
      wild type enzyme, whereas their ATPase activity is impaired. These results
      clearly show that the helicase motifs are tightly involved in the coupling of ATP
      hydrolysis to the topoisomerase activity. The zinc finger motif located at the N
      terminal end of reverse gyrases was also mutated. Our results indicate that this
      motif plays an important role in DNA binding.

PMID- 18614531
TI  - Identification and functional characterization of adipose-specific phospholipase
      A2 (AdPLA).
AB  - Phospholipases A(2) (PLA(2)s) catalyze hydrolysis of fatty acids from the sn-2
      position of phospholipids. Here we report the identification and characterization
      of a membrane-associated intracellular calcium-dependent, adipose-specific PLA(2)
      that we named AdPLA (adipose-specific phospholipase A(2)). We found that AdPLA
      was highly expressed specifically in white adipose tissue and was induced during
      preadipocyte differentiation into adipocytes. Clearance of AdPLA by
      immunoprecipitation significantly decreased PLA activity in white adipose tissue
      lysates but had no effect on liver lysates, where expression was hardly
      detectable. In characterizing AdPLA, we employed radiochemical assays with TLC
      analysis of the enzyme activity of lysates from COS-7 cells overexpressing AdPLA.
      For kinetic studies, we produced purified recombinant AdPLA for use in a
      lipoxidase-coupled spectrophotometric assay. AdPLA generated free fatty acid and
      lysophospholipid from phosphatidylcholine with a preference for hydrolysis at the
      sn-2 position. Although we found low but detectable lysophospholipase activity,
      AdPLA showed no significant activity against a variety of other lipid substrates.
      Calcium was found to activate AdPLA but was not essential for activity. Studies
      with known phospholipase inhibitors, including bromoenolactone, methyl
      arachidonyl fluorophosphate, AACOCF(3), 7,7-dimethyl-5,8-eicosadienoic acid, and
      thioetheramide, supported that AdPLA is a phospholipase. Mutational studies
      showed that His-23 and Cys-113 are critical for activity of AdPLA and suggested
      that AdPLA is likely a His/Cys PLA(2). Overall, although AdPLA is similar to
      other histidine phospholipases in pH and calcium dependence, AdPLA showed
      different characteristics in many regards, including predicted catalytic
      mechanism. AdPLA may therefore represent the first member of a new group of
      PLA(2)s, group XVI.

PMID- 18614532
TI  - Multiple cyclin kinase inhibitors promote bile acid-induced apoptosis and
      autophagy in primary hepatocytes via p53-CD95-dependent signaling.
AB  - Previously, using primary hepatocytes residing in early G1 phase, we demonstrated
      that expression of the cyclin-dependent kinase (CDK) inhibitor protein p21Cip
      1/WAF1/mda6 (p21) enhanced the toxicity of deoxycholic acid (DCA) + MEK1/2
      inhibitor. This study examined the mechanisms regulating this apoptotic process.
      Overexpression of p21 or p27(Kip-1) (p27) enhanced DCA + MEK1/2 inhibitor
      toxicity in primary hepatocytes that was dependent on expression of acidic
      sphingomyelinase and CD95. Overexpression of p21 suppressed MDM2, elevated p53
      levels, and enhanced CD95, BAX, NOXA, and PUMA expression; knockdown of
      BAX/NOXA/PUMA reduced CDK inhibitor-stimulated cell killing. Parallel to cell
      death processes, overexpression of p21 or p27 profoundly enhanced DCA + MEK1/2
      inhibitor-induced expression of ATG5 and GRP78/BiP and phosphorylation of PKR
      like endoplasmic reticulum kinase (PERK) and eIF2alpha, and it increased the
      numbers of vesicles containing a transfected LC3-GFP construct. Incubation of
      cells with 3-methyladenine or knockdown of ATG5 suppressed DCA + MEK1/2 inhibitor
      induced LC3-GFP vesicularization and enhanced DCA + MEK1/2 inhibitor-induced
      toxicity. Expression of dominant negative PERK blocked DCA + MEK1/2 inhibitor
      induced expression of ATG5, GRP78/BiP, and eIF2alpha phosphorylation and
      prevented LC3-GFP vesicularization. Knock-out or knockdown of p53 or CD95
      abolished DCA + MEK1/2 inhibitor-induced PERK phosphorylation and prevented LC3
      GFP vesicularization. Thus, CDK inhibitors suppress MDM2 levels and enhance p53
      expression that facilitates bile acid-induced, ceramide-dependent CD95 activation
      to induce both apoptosis and autophagy in primary hepatocytes.

PMID- 18614533
TI  - A block in endoplasmic reticulum-to-Golgi trafficking inhibits phospholipid
      synthesis and induces neutral lipid accumulation.
AB  - Seeking to better understand how membrane trafficking is coordinated with
      phospholipid synthesis in yeast, we investigated lipid synthesis in several Sec(
      ) temperature-sensitive mutants, including sec13-1. Upon shift of sec13-1 cells
      to the restrictive temperature of 37 degrees C, phospholipid synthesis decreased
      dramatically relative to the wild type control, whereas synthesis of neutral
      lipids, especially triacylglycerol (TAG), increased. When examined by
      fluorescence microscopy, the number of lipid droplets appeared to increase and
      formed aggregates in sec13-1 cells shifted to 37 degrees C. Electron microscopy
      confirmed the increase in lipid droplet number and revealed that many were
      associated with the vacuole. Analysis of lipid metabolism in strains lacking TAG
      synthase genes demonstrated that the activities of the products of these genes
      contribute to accumulation of TAG in sec13-1 cells after the shift to 37 degrees
      C. Furthermore, the permissive temperature for growth of the sec13-1 strain
      lacking TAG synthase genes was 3 degrees C lower than sec13-1 on several
      different growth media, indicating that the synthesis of TAG has physiological
      significance under conditions of secretory stress. Together these results suggest
      that following a block in membrane trafficking, yeast cells channel lipid
      metabolism from phospholipid synthesis into synthesis of TAG and other neutral
      lipids to form lipid droplets. We conclude that this metabolic switch provides a
      degree of protection to cells during secretory stress.

PMID- 18614534
TI  - On the oxygen reactivity of flavoprotein oxidases: an oxygen access tunnel and
      gate in brevibacterium sterolicum cholesterol oxidase.
AB  - The flavoprotein cholesterol oxidase from Brevibacterium sterolicum (BCO)
      possesses a narrow channel that links the active center containing the flavin to
      the outside solvent. This channel has been proposed to serve for the access of
      dioxygen; it contains at its "bottom" a Glu-Arg pair (Glu-475-Arg-477) that was
      found by crystallographic studies to exist in two forms named "open" and
      "closed," which in turn was suggested to constitute a gate functioning in the
      control of oxygen access. Most mutations of residues that flank the channel have
      minor effects on the oxygen reactivity. Mutations of Glu-311, however, cause a
      switch in the basic kinetic mechanism of the reaction of reduced BCO with
      dioxygen; wild-type BCO and most mutants show a saturation behavior with
      increasing oxygen concentration, whereas for Glu-311 mutants a linear dependence
      is found that is assumed to reflect a "simple" second order process. This is
      taken as support for the assumption that residue Glu-311 finely tunes the Glu-475
      Arg-477 pair, forming a gate that functions in modulating the access/reactivity
      of dioxygen.

PMID- 18614535
TI  - KIF1Bbeta functions as a haploinsufficient tumor suppressor gene mapped to
      chromosome 1p36.2 by inducing apoptotic cell death.
AB  - Deletion of the distal region of chromosome 1 frequently occurs in a variety of
      human cancers, including aggressive neuroblastoma. Previously, we have identified
      a 500-kb homozygously deleted region at chromosome 1p36.2 harboring at least six
      genes in a neuroblastoma-derived cell line NB1/C201. Among them, only KIF1Bbeta,
      a member of the kinesin superfamily proteins, induced apoptotic cell death. These
      results prompted us to address whether KIF1Bbeta could be a tumor suppressor gene
      mapped to chromosome 1p36 in neuroblastoma. Hemizygous deletion of KIF1Bbeta in
      primary neuroblastomas was significantly correlated with advanced stages (p =
      0.0013) and MYCN amplification (p < 0.001), whereas the mutation rate of the
      KIF1Bbeta gene was infrequent. Although KIF1Bbeta allelic loss was significantly
      associated with a decrease in KIF1Bbeta mRNA levels, its promoter region was not
      hypermethylated. Additionally, expression of KIF1Bbeta was markedly down
      regulated in advanced stages of tumors (p < 0.001). Enforced expression of
      KIF1Bbeta resulted in an induction of apoptotic cell death in association with an
      increase in the number of cells entered into the G2/M phase of the cell cycle,
      whereas its knockdown by either short interfering RNA or by a genetic suppressor
      element led to an accelerated cell proliferation or enhanced tumor formation in
      nude mice, respectively. Furthermore, we demonstrated that the rod region unique
      to KIF1Bbeta is critical for the induction of apoptotic cell death in a p53
      independent manner. Thus, KIF1Bbeta may act as a haploinsufficient tumor
      suppressor, and its allelic loss may be involved in the pathogenesis of
      neuroblastoma and other cancers.

PMID- 18614536
TI  - Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin
      proteasome-dependent degradation of rhodopsin during retinal inflammation.
AB  - Inflammatory cytokines cause tissue dysfunction. We previously reported that
      retinal inflammation down-regulates rhodopsin expression and impairs visual
      function by an unknown mechanism. Here, we demonstrate that rhodopsin levels were
      preserved by suppressor of cytokine signaling 3 (SOCS3), a negative feedback
      regulator of STAT3 activation. SOCS3 was expressed mainly in photoreceptor cells
      in the retina. In the SOCS3-deficient retinas, rhodopsin protein levels dropped
      sooner, and the reduction was more profound than in the wild type. Visual
      dysfunction, measured by electroretinogram, was prolonged in retina-specific
      SOCS3 conditional knock-out mice. Visual dysfunction and decreased rhodopsin
      levels both correlated with increased STAT3 activation enhanced by SOCS3
      deficiency. Interleukin 6, one of the inflammatory cytokines found during retinal
      inflammation, activated STAT3 and decreased rhodopsin protein in adult retinal
      explants. This was enhanced by inhibiting SOCS3 function in vitro, indicating
      that rhodopsin reduction was not a secondary effect in the mutant mice.
      Interestingly, in the inflamed SOCS3-deficient adult retina, rhodopsin decreased
      post-transcriptionally at least partly through ubiquitin-proteasome-dependent
      degradation accelerated by STAT3 activation and not transcriptionally as in the
      developing retina, on which we reported previously. A STAT3-dependent E3
      ubiquitin ligase, Ubr1, was responsible for rhodopsin degradation and was up
      regulated in the inflamed SOCS3-deficient retinas. These results indicate that in
      wild-type animals, a decrease in rhodopsin during inflammation is minimized by
      endogenous SOCS3. However, when STAT3 activation exceeds some threshold beyond
      the compensatory activity of endogenous SOCS3, rhodopsin levels decrease. These
      findings suggest SOCS3 as a potential therapeutic target molecule for protecting
      photoreceptor cell function during inflammation.

PMID- 18614537
TI  - Diacylglycerol specifically blocks spontaneous integration of membrane proteins
      and allows detection of a factor-assisted integration.
AB  - We recently found that the spontaneous integration of M13 procoat is blocked by
      diacylglycerol (DAG) (Nishiyama, K., Ikegami, A., Moser, M., Schiltz, E., Tokuda,
      H., and Muller, M. (2006) J. Biol. Chem. 281, 35667-35676). Here, we demonstrate
      that the spontaneous integration of Pf3 coat, another membrane protein that has
      been thought to be integrated spontaneously into liposomes, can be blocked by DAG
      at physiological concentrations. Moreover, the spontaneous integration of the
      membrane potential-independent version of Pf3 coat (3L-Pf3 coat), which is
      independent of YidC, was also blocked by DAG. To clarify the mechanism by which
      DAG blocks spontaneous integration, we examined lipid compounds similar to DAG
      and DAG derivatives. The blockage of spontaneous integration was specific to DAG,
      as fatty acids, monoacylglycerol, and phosphatidic acids were not effective for
      the blockage. When the acyl chains in DAG were shortened even to octanoyl
      residues, it still blocked spontaneous integration, whereas diheptanoylglycerol
      did not block it at all. Triacylglycerol was more effective than DAG. However,
      the lipid A-derivative-dependent integration of M13 procoat could not be
      reconstituted when triacylglycerol was included in the liposomes. On the other
      hand, when DAG was included in the liposomes, we found that the integration of 3L
      Pf3 coat was strictly dependent on the lipid A-derived integration factor. We
      propose that the bulky structure of DAG rather than changes in membrane curvature
      is essential for the blockage of spontaneous integration. We also demonstrated
      that the blockage of spontaneous integration by DAG is also operative in native
      membrane vesicles.

PMID- 18614538
TI  - Kinetic mechanism for assembly of the m7GpppG.eIF4E.eIF4G complex.
AB  - Interaction of the mRNA cap with the translational machinery is a critical and
      early step in the initiation of protein synthesis. To better understand this
      process, we determined kinetic constants for the interaction of m(7)GpppG with
      human eIF4E by stopped-flow fluorescence quenching in the presence of a 90-amino
      acid fragment of human eIF4G that contains the eIF4E-binding domain (eIF4G(557
      646)). The values obtained, k(on) = 179 x 10(6) m(-1) s(-1) and k(off) = 79 s(
      1), were the same as reported previously in the absence of an eIF4G-derived
      peptide. We also used surface plasmon resonance to determine kinetic constants
      for the binding of eIF4E to eIF4G(557-646), both in the presence and absence of
      m(7)GpppG. The results indicated that eIF4G(557-646) binds eIF4E and
      eIF4E.m(7)GpppG at the same rate, with k(on) = 3 x 10(6) m(-1) s(-1) and k(off) =
      0.01 s(-1). Our data represent the first full kinetic description of the
      interaction of eIF4E with its two specific ligands. The results demonstrate that
      the formation of the m(7)GpppG.eIF4E.eIF4G(557-646) complex obeys a sequential,
      random kinetic mechanism and that there is no preferential pathway for its
      formation. Thus, even though eIF4G(557-646) binds eIF4E tightly, it does not
      increase the affinity of eIF4E for m(7)GpppG, as has been claimed in several
      previous publications. We did, in fact, observe increased binding to m(7)GTP
      Sepharose in the presence of eIF4G(557-646), but only with recombinant eIF4E that
      was prepared from inclusion bodies.

PMID- 18614539
TI  - Rho Family GTPase modification and dependence on CAAX motif-signaled
      posttranslational modification.
AB  - Rho GTPases (20 human members) comprise a major branch of the Ras superfamily of
      small GTPases, and aberrant Rho GTPase function has been implicated in
      oncogenesis and other human diseases. Although many of our current concepts of
      Rho GTPases are based on the three classical members (RhoA, Rac1, and Cdc42),
      recent studies have revealed the diversity of biological functions mediated by
      other family members. A key basis for the functional diversity of Rho GTPases is
      their association with distinct subcellular compartments, which is dictated in
      part by three posttranslational modifications signaled by their carboxyl-terminal
      CAAX (where C represents cysteine, A is an aliphatic amino acid, and X is a
      terminal amino acid) tetrapeptide motifs. CAAX motifs are substrates for the
      prenyltransferase-catalyzed addition of either farnesyl or geranylgeranyl
      isoprenoid lipids, Rce1-catalyzed endoproteolytic cleavage of the AAX amino
      acids, and Icmt-catalyzed carboxyl methylation of the isoprenylcysteine. We
      utilized pharmacologic, biochemical, and genetic approaches to determine the
      sequence requirements and roles of CAAX signal modifications in dictating the
      subcellular locations and functions of the Rho GTPase family. Although the
      classical Rho GTPases are modified by geranylgeranylation, we found that a
      majority of the other Rho GTPases are substrates for farnesyltransferase. We
      found that the membrane association and/or function of Rho GTPases are
      differentially dependent on Rce1- and Icmt-mediated modifications. Our results
      further delineate the sequence requirements for prenyltransferase specificity and
      functional roles for protein prenylation in Rho GTPase function. We conclude that
      a majority of Rho GTPases are targets for pharmacologic inhibitors of
      farnesyltransferase, Rce1, and Icmt.

PMID- 18614540
TI  - Design of the artificial acellular feeder layer for the efficient propagation of
      mouse embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent-undifferentiated cells that have a
      great interest for the investigation of developmental biology. Murine ES cells
      maintain their pluripotency by the supplementation of the leukemia inhibitory
      factor (LIF). LIF is reported to act as a matrix-anchored form, and immobilized
      cytokines are useful to sustain their signaling on target cells. In this study,
      we used the immobilizable fusion protein composed of LIF and IgG-Fc region, which
      was used as a model of the matrix-anchored form of LIF to establish a novel
      system for ES cell culture and to investigate the effect of immobilized LIF on
      maintenance of ES cell pluripotency. Mouse ES cells maintained their
      undifferentiated state on the surface coated with LIF-Fc. Furthermore, when
      cultured on the co-immobilized surface with LIF-Fc and E-cadherin-Fc, mouse ES
      cells showed characteristic scattering morphologies without colony formation, and
      they could maintain their undifferentiated state and pluripotency without
      additional LIF supplementation. The activation of LIF signaling was sustained on
      the co-immobilized surface. These results indicate that immobilized LIF and E
      cadherin can maintain mouse ES cells efficiently and that the immobilizable LIF
      Fc fusion protein is useful for the investigation of signaling pathways of an
      immobilized form of LIF in the maintenance of ES cell pluripotency.

PMID- 18614541
TI  - Transforming growth factor-beta requires its target plasminogen activator
      inhibitor-1 for cytostatic activity.
AB  - The cytokine transforming growth factor beta (TGFbeta) has strong
      antiproliferative activity in most normal cells but contributes to tumor
      progression in the later stages of oncogenesis. It is not fully understood which
      TGFbeta target genes are causally involved in mediating its cytostatic activity.
      We report here that suppression of the TGFbeta target gene encoding plasminogen
      activator inhibitor-1 (PAI-1) by RNA interference leads to escape from the
      cytostatic activity of TGFbeta both in human keratinocytes (HaCaTs) and primary
      mouse embryo fibroblasts. Consistent with this, PAI-1 knock-out mouse embryo
      fibroblasts are also resistant to TGFbeta growth arrest. Conversely, we show that
      ectopic expression of PAI-1 in proliferating HaCaT cells induces a growth arrest.
      PAI-1 knockdown does not interfere with canonical TGFbeta signaling as judged by
      SMAD phosphorylation and induction of bona fide TGFbeta target genes. Instead,
      knockdown of PAI-1 results in sustained activation of protein kinase B.
      Significantly, we find that constitutive protein kinase B activity leads to
      evasion of the growth-inhibitory action of TGFbeta. Our data are consistent with
      a model in which induction of PAI-1 by TGFbeta is critical for the induction of
      proliferation arrest.

PMID- 18614542
TI  - The structure of the GAF A domain from phosphodiesterase 6C reveals determinants
      of cGMP binding, a conserved binding surface, and a large cGMP-dependent
      conformational change.
AB  - The photoreceptor phosphodiesterase (PDE6) regulates the intracellular levels of
      the second messenger cGMP in the outer segments of cone and rod photoreceptor
      cells. PDE6 contains two regulatory GAF domains, of which one (GAF A) binds cGMP
      and regulates the activity of the PDE6 holoenzyme. To increase our understanding
      of this allosteric regulation mechanism, we present the 2.6A crystal structure of
      the cGMP-bound GAF A domain of chicken cone PDE6. Nucleotide specificity appears
      to be provided in part by the orientation of Asn-116, which makes two hydrogen
      bonds to the guanine ring of cGMP but is not strictly conserved among PDE6
      isoforms. The isolated PDE6C GAF A domain is monomeric and does not contain
      sufficient structural determinants to form a homodimer as found in full-length
      PDE6C. A highly conserved surface patch on GAF A indicates a potential binding
      site for the inhibitory subunit Pgamma. NMR studies reveal that the apo-PDE6C GAF
      A domain is structured but adopts a significantly altered structural state
      indicating a large conformational change with rearrangement of secondary
      structure elements upon cGMP binding. The presented crystal structure will help
      to define the cGMP-dependent regulation mechanism of the PDE6 holoenzyme and its
      inhibition through Pgamma binding.

PMID- 18614543
TI  - The 5q31 variants associated with psoriasis and Crohn's disease are distinct.
AB  - Predisposition to psoriasis is known to be affected by genetic variation in HLA
      C, IL12B and IL23R, but other genetic risk factors also exist. We recently
      reported three psoriasis-associated single nucleotide polymorphisms (SNPs) in the
      5q31 locus, a region of high linkage disequilibrium laden with inflammatory
      pathway genes. The aim of this study was to assess whether other variants in the
      5q31 region are causal to these SNPs or make independent contributions to
      psoriasis risk by genotyping a comprehensive set of tagging SNPs in a 725 kb
      region bounded by IL3 and IL4 and testing for disease association. Ninety SNPs,
      capturing 86.4% of the genetic diversity, were tested in one case-control sample
      set (467 cases/460 controls) and significant markers (P(allelic) < 0.05) (n = 9)
      were then tested in two other sample sets (981 cases/925 controls). All nine SNPs
      were significant in a meta-analysis of the combined sample sets. Pair-wise
      conditional association tests showed rs1800925, an intergenic SNP located just
      upstream of IL13 (Mantel-Haenszel P(combined) = 1.5 x 10(-4), OR = 0.77 [0.67
      0.88]), could account for observed significant association of all but one other
      SNP, rs11568506 in SLC22A4 [Mantel-Haenszel P(combined) = 0.043, OR = 0.68 (0.47
      0.99)]. Haplotype analysis of these two SNPs showed increased significance for
      the two common haplotypes (rs11568506-rs1800925: GC, P(combined) = 5.67 x 10(-6),
      OR = 1.37; GT, P(combined) = 6.01 x 10(-5), OR = 0.75; global haplotype P = 8.93
      x 10(-5)). Several 5q31-region SNPs strongly associated with Crohn's disease (CD)
      in the recent WTCCC study were not significant in the psoriasis sample sets
      tested here. These results identify the most significant 5q31 risk variants for
      psoriasis and suggest that distinct 5q31 variants contribute to CD and psoriasis
      risk.

PMID- 18614545
TI  - First evidence for an association of a functional variant in the microRNA-510
      target site of the serotonin receptor-type 3E gene with diarrhea predominant
      irritable bowel syndrome.
AB  - Diarrhea predominant irritable bowel syndrome (IBS-D) is a complex disorder
      related to dysfunctions in the serotonergic system. As cis-regulatory variants
      can play a role in the etiology of complex conditions, we investigated the
      untranslated regions (UTRs) of the serotonin receptor type 3 subunit genes HTR3A
      and HTR3E. Mutation analysis was carried out in a pilot sample of 200 IBS
      patients and 100 healthy controls from the UK. The novel HTR3E 3'-UTR variant
      c.*76G>A (rs62625044) was associated with female IBS-D (P = 0.033, OR = 8.53).
      This association was confirmed in a replication study, including 119 IBS-D
      patients and 195 controls from Germany (P = 0.0046, OR = 4.92). Pooled analysis
      resulted in a highly significant association of c.*76G>A with female IBS-D (P =
      0.0002, OR = 5.39). In a reporter assay, c.*76G>A affected binding of miR-510 to
      the HTR3E 3'-UTR and caused elevated luciferase expression. HTR3E and miR-510 co
      localize in enterocytes of the gut epithelium as shown by in situ hybridization
      and RT-PCR. This is the first example indicating micro RNA-related expression
      regulation of a serotonin receptor gene with a cis-regulatory variant affecting
      this regulation and appearing to be associated with female IBS-D.

PMID- 18614544
TI  - Neurofibromin regulates somatic growth through the hypothalamic-pituitary axis.
AB  - To study the role of the neurofibromatosis-1 (NF1) gene in mammalian brain
      development, we recently generated mice in which Nf1 gene inactivation occurs in
      neuroglial progenitor cells using the brain lipid binding protein (BLBP)
      promoter. We found that Nf1(BLBP)CKO mice exhibit significantly reduced body
      weights and anterior pituitary gland sizes. We further demonstrate that the small
      anterior pituitary size reflects loss of neurofibromin expression in the
      hypothalamus, leading to reduced growth hormone releasing hormone, pituitary
      growth hormone (GH) and liver insulin-like growth factor-1 (IGF1) production.
      Since neurofibromin both negatively regulates Ras activity and positively
      modulates cAMP levels, we examined the signaling pathway responsible for these
      abnormalities. While BLBP-mediated expression of an activated Ras molecule did
      not recapitulate the body weight and hypothalamic/pituitary defects, treatment of
      Nf1(BLBP)CKO mice with rolipram to increase cAMP levels resulted in a partial
      restoration of the body weight phenotype. Furthermore, conditional expression of
      the Ras regulatory GAP domain of neurofibromin also did not rescue the body
      weight or Igf1 mRNA defects in Nf1(BLBP)CKO mice. Collectively, these data
      demonstrate a critical role for neurofibromin in hypothalamic-pituitary axis
      function and provide further insights into the short stature and GH deficits seen
      in children with NF1.

PMID- 18614546
TI  - Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2:
      rapamycin triggers dephosphorylation and delocalization of the mTORC2 components
      rictor and sin1.
AB  - The mammalian target of rapamycin (mTOR) is part of two distinct complexes,
      mTORC1, containing raptor and mLST8, and mTORC2, containing rictor, mLST8 and
      sin1. Although great endeavors have already been made to elucidate the function
      and regulation of mTOR, the cytoplasmic nuclear distribution of the mTOR
      complexes is unknown. Upon establishment of the proper experimental conditions,
      we found mTOR, mLST8, rictor and sin1 to be less abundant in the nucleus than in
      the cytoplasm of non-transformed, non-immortalized, diploid human primary
      fibroblasts. Although raptor is also high abundant in the nucleus, the
      mTOR/raptor complex is predominantly cytoplasmic, whereas the mTOR/rictor complex
      is abundant in both compartments. Rapamycin negatively regulates the formation of
      both mTOR complexes, but the molecular mechanism of its effects on mTORC2
      remained elusive. We describe that in primary cells short-term treatment with
      rapamycin triggers dephosphorylation of rictor and sin1 exclusively in the
      cytoplasm, but does not affect mTORC2 assembly. Prolonged drug treatment leads to
      complete dephosphorylation and cytoplasmic translocation of nuclear rictor and
      sin1 accompanied by inhibition of mTORC2 assembly. The distinct cytoplasmic and
      nuclear upstream and downstream effectors of mTOR are involved in many cancers
      and human genetic diseases, such as tuberous sclerosis, Peutz-Jeghers syndrome,
      von Hippel-Lindau disease, neurofibromatosis type 1, polycystic kidney disease,
      Alzheimer's disease, cardiac hypertrophy, obesity and diabetes. Accordingly,
      analogs of rapamycin are currently tested in many different clinical trials. Our
      data allow new insights into the molecular consequences of mTOR dysregulation
      under pathophysiological conditions and should help to optimize rapamycin
      treatment of human diseases.

PMID- 18614547
TI  - NOTES: transvaginal for cancer diagnostic staging: preliminary clinical
      application.
AB  - Laparoscopy is now a reliable method for staging gastrointestinal cancer,
      orienting the therapy, and avoiding unnecessary laparotomy. Natural orifice
      transluminal endoscopic surgery (NOTES) is an emerging concept with potential
      advantages for patient recovery. The first case of clinical diagnostic
      application of transvaginal NOTES for diagnostic cancer staging is presented.
      Informed consent and Institutional Commission approval were obtained for
      transvaginal clinical trials. On February 28, 2007, a patient with elective
      surgical indication for diagnostic cancer staging was submitted to transvaginal
      NOTES procedure, and intra- and postoperative parameters were documented. In a 50
      year-old female patient presenting with ascitis, diffuse abdominal pain, and
      weight loss for 2 months, diagnosis of peritoneal carcinomatosis was suspected,
      which was also found when a CT scan was performed. Transvaginal NOTES was used
      for diagnostic staging of the patient, using a colonoscope introduced into the
      abdomen through a small incision in the vagina. Biopsies of liver, diaphragm,
      ovaries, and peritoneum were successfully performed. Operative time was 105 min,
      vaginal access and closure was obtained in 15 min. Abdominal inventory was
      reliable, and all 16 biopsies taken were positive for ovarian adenocarcinoma. The
      patient was dismissed 48 hours after the procedure without complications. Recent
      literature and experience of the study group suggest possibilities for
      preliminary clinical applications by transvaginal natural orifice surgery for
      diagnostic purposes.

PMID- 18614548
TI  - MicroRNAs: components of an integrated system controlling cardiac development,
      physiology, and disease pathogenesis.

PMID- 18614549
TI  - Control of cardiac excitability by microRNAs.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in
      developed countries. The pathological process of the heart is associated with an
      altered expression profile of genes that are important for cardiac function.
      MicroRNAs (miRNAs) have recently emerged as one of the central players of gene
      expression regulation. The implications of miRNAs in the pathological process of
      the cardiovascular system have recently been recognized, and research on miRNAs
      in relation to cardiovascular disease has now become a most rapidly evolving
      field. In this review, we focus on miRNAs and control of cardiac excitability,
      aiming to provide a comprehensive overview on the available experimental data on
      regulation of cardiac conduction, repolarization, and automaticity by miRNAs.
      Aberrant expression of miRNAs in the diseased state of the heart and their
      arrhythmogenic or anti-arrhythmic potential will be discussed. Finally, the
      innovative miRNA-interference technologies developed lately for manipulating the
      action of miRNAs by interfering with their expression, stability, and function as
      new approaches for miRNA research and gene therapy will be introduced.

PMID- 18614550
TI  - Amplatzer occlusion of paravalvular leak of mitral mechanical prosthesis
      following a reoperation for thrombosed mitral mechanical prosthesis.
AB  - We describe a case of a 46-year-old woman with dehiscence and paravalvular leak
      of a second-time replaced mitral mechanical prosthesis, successfully treated with
      Amplatzer occlusion of the paravalvular leak, thus avoiding a second reoperation
      and improving the patient's symptoms.

PMID- 18614551
TI  - Incidence of atrial fibrillation after extrapleural pneumonectomy vs. pleurectomy
      in patients with malignant pleural mesothelioma.
AB  - Extrapleural pneumonectomy (EPP) and pleurectomy are the surgical procedures for
      the treatment of pleural mesothelioma. However, EPP increases the risk for
      postoperative atrial fibrillation (AF). We conducted a retrospective chart review
      of 130 patients who underwent EPP or pleurectomy. Seventy patients (excluding
      three patients with a prior history of AF) underwent EPP and 57 patients
      underwent pleurectomy. The mean ages were 60+/-11 and 63+/-13 years, and the male
      to female ratios were 50/20 and 44/13, respectively. Postoperative AF was
      observed in 45 patients with 36 (51%) of these cases occurring after EPP and 9
      (17%) after pleurectomy (P<0.0001). There were no significant differences between
      the two treatment groups for gender, age, side of affected lung, preoperative
      heart rate, history of beta-blocker use, coronary heart disease, and chronic
      obstructive pulmonary disease. Through logistic regression, EPP (OR=7.1, 95% CI:
      2.9, 17.8) and age over 65 years (OR=2.9, 95% CI: 1.2, 6.8) were found to be risk
      factors for AF. We conclude that EPP vs. pleurectomy and age over 65 years are
      risk factors for postoperative AF. The increased odds of having AF after EPP
      could be due to right heart stress caused by pneumonectomy.

PMID- 18614552
TI  - Spontaneous left main coronary artery dissection.
AB  - Spontaneous coronary artery dissection is a rare and generally fatal disease. A
      review of the literature demonstrates that the aetiopathogenesis of the disease
      is unknown and that the histology is rarely described. It usually occurs in young
      women during the post-partum period or while taking oral contraceptives. The
      treatment depends on the clinical presentation and the results of the
      angiography. We report here a case of spontaneous dissection of the left main
      stem coronary artery, with extension into the left coronary territory which which
      occurred in a 43-year-old woman.

PMID- 18614553
TI  - Biventricular pacing for end-stage heart failure: early experience in surgical
      vs. transvenous left ventricular lead placement.
AB  - Transvenous coronary sinus lead placement is currently the standard approach for
      left ventricular pacing. The aim of this study is to assess whether a mini
      thoracotomy approach would be feasible and safe when used for cases in which
      transvenous procedures were ineffective or judged unlikely to succeed.
      Biventricular pacing was performed in 138 consecutive patients with 47 patients
      undergoing a mini-thoracotomy procedure. NYHA status, quality of life, electrical
      and echocardiographic data were assessed in the two groups over a follow-up
      period of 17.6+/-4.2 weeks. There was no significant difference in the
      preoperative characteristics in both groups other than a greater prevalence of
      renal failure and previous cardiac surgery among the surgical patients. The mean
      procedure time was significantly longer in the transvenous group. No significant
      differences were noted in the immediate or long-term pacing parameters. Two
      mortalities were observed in the surgical group >2 weeks following the procedure.
      During the follow-up period, we noted a comparable improvement in the
      echocardiographic parameters, QRS duration and NYHA status with both approaches.
      Our results suggest that even when performed on high-risk patients, epicardial
      lead placement through a mini-thoracotomy is beneficial and feasible as a
      'rescue' procedure after a failed transvenous approach.

PMID- 18614554
TI  - Treatment of tinnitus with a customized, dynamic acoustic neural stimulus:
      underlying principles and clinical efficacy.
AB  - Tinnitus has been challenging to treat with consistently positive results. The
      Neuromonics Tinnitus Treatment is a newly available approach to the treatment of
      clinically significant, problematic tinnitus (and reduced sound tolerance) that
      was developed with the intention of simultaneously addressing the auditory,
      attentional, and emotional processes underlying the condition. It uses a
      prescribed acoustic stimulus, customized for each patient's individual
      audiometric profile, which provides a broad frequency stimulus to address the
      effects of auditory deprivation, promotes relief and relaxation with the
      intention of reducing engagement of the limbic system/amygdala and autonomic
      nervous system, and applies the principles of systematic desensitization to
      address the attentional processes. This article describes the underlying
      principles behind this approach. It also summarizes evidence for clinical
      efficacy from controlled clinical studies and from a private practice clinical
      setting, where it has been shown to provide consistently positive outcomes for
      patients meeting suitability criteria.

PMID- 18614555
TI  - Pleural drainage and pleurodesis: implementation of guidelines in four hospitals.
AB  - The aim of the present study was to evaluate the implementation of the 2003 Dutch
      guideline on the diagnosis and treatment of malignant pleural effusions, and the
      potential effect of the implementation on the clinical outcome of pleurodesis.
      All patients with malignant pleural effusion who had a pleural drain placed with
      the intention of performing pleurodesis were registered prospectively in four
      centres. Details of the procedure and fluid recurrence and survival data were
      noted. Patients with a proven malignancy (n = 100) were entered into the
      registration database. Diagnostic guideline recommendations were followed in 60
      70% of the patients. Surprisingly, pleurodesis was performed in only 75% of the
      patients, mainly due to the presence of a trapped lung. All pleurodeses were
      performed using talc, according to the guideline. Follow-up revealed fluid
      recurrence in 27 (36%) patients after a mean follow-up of 17 days (range 2-285
      days); 14 patients with successful pleurodesis died with a median survival of 61
      days (range 13-174 days). Systemic treatment following pleurodesis and good
      apposition of the pleural surfaces during drainage were good prognostic factors.
      Despite reasonable-to-good adherence to the guideline, the number of successful
      pleurodeses was low. Better predictors of a good pleurodesis outcome are needed.

PMID- 18614556
TI  - Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury
      in mice.
AB  - Reactive oxygen species play an important role in the pathogenesis of acute lung
      injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a
      free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury
      in mice by decreasing oxidative stress. Lung injury was induced in female ICR
      mice by intratracheal instillation of 5 mg x kg(-1) of BLM. Edaravone (300 mg x
      kg(-1)) was administered by intraperitoneal administration 1 h before BLM
      challenge. Edaravone significantly improved the survival rate of mice treated
      with BLM from 25 to 90%, reduced the number of total cells and neutrophils in
      bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations
      of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the
      lung on day 28 was ameliorated by edaravone, as evaluated by histological
      examination and measurement of hydroxyproline contents. In addition, edaravone
      significantly increased the prostaglandin E(2) concentration in BALF on day 2. In
      summary, edaravone was shown to inhibit lung injury and fibrosis via the
      repression of lipid hydroperoxide production and the elevation of prostaglandin
      E(2) production in the present experimental murine system.

PMID- 18614557
TI  - Frequency and peak stretch magnitude affect alveolar epithelial permeability.
AB  - The present study measured stretch-induced changes in transepithelial
      permeability to uncharged tracers (1.5-5.5 A) using cultured monolayers of
      alveolar epithelial type-I like cells. Cultured alveolar epithelial cells were
      subjected to uniform cyclic (0, 0.25 and 1.0 Hz) biaxial stretch from 0% to 12,
      25 or 37% change in surface area (DeltaSA) for 1 h. Significant changes in
      permeability of cell monolayers were observed when stretched from 0% to 37%
      DeltaSA at all frequencies, and from 0% to 25% DeltaSA only at high frequency (1
      Hz), but not at all when stretched from 0% to 12% DeltaSA compared with
      unstretched controls. At stretch oscillation amplitudes of 25 and 37% DeltaSA,
      imposed at 1 Hz, tracer permeability increased compared with that at 0.25 Hz.
      Cells subjected to a single stretch cycle at 37% DeltaSA (0.25 Hz), to simulate a
      deep sigh, were not distinguishable from unstretched controls. Reducing stretch
      oscillation amplitude while maintaining a peak stretch of 37% DeltaSA (0.25 Hz)
      via the application of a simulated post-end-expiratory pressure did not protect
      barrier properties. In conclusion, peak stretch magnitude and stretch frequency
      were the primary determining factors for epithelial barrier dysfunction, as
      opposed to oscillation amplitude.

PMID- 18614558
TI  - Happiness to be gained in paediatric asthma care.
AB  - The aim of the present study was to establish the efficacy in terms of morbidity
      and health-related quality of life (HRQoL) of a group asthma education-exercise
      programme to children with low (below 10th percentile value) quality-of-life
      scores. A controlled, randomised, open, clinical trial was conducted. In total,
      36 out of 53 unhappy children, among 204 (68%) respondents, treated in four
      paediatric practices, enrolled (mean age 10 yrs; range: 8-12 yrs), after random
      allocation in control and intervention groups (child, parent, teacher).
      Measurements were taken at baseline (T0) and after 3, 6 (T6) and 9 months (T9;
      intervention group only at 9 months). All but four controls completed the study.
      From T0-T6, changes (Delta) in HRQoL were clinically important and significantly
      greater in the intervention group than in the control group, both for generic
      HRQoL (effect size (ES) 0.95; Delta 16%+/-12% versus -1+/-4%) and for asthma
      specific HRQoL (ES 0.58; Delta 15%+/-17% versus 1.5+/-14%). T9 measurements were
      consistent with T6 findings. Changes in sick days (ES 0.78), oral prednisone
      courses (ES 0.71) and doctor visits (ES 0.74) over a 6-month period were greater
      in the intervention group than in the control group. Changes could not be
      ascribed to change in lung function or medication. In unhappy children, quality
      of life and morbidity may improve with a low intensity asthma education-exercise
      programme, even without gains in pulmonary function or exercise tolerance.

PMID- 18614559
TI  - Pulmonary tuberculosis with acute respiratory failure.
AB  - The aim of the present study was to evaluate the clinical characteristics,
      prognoses and predictors of mortality of patients with pulmonary tuberculosis
      (TB) with acute respiratory failure (ARF), and to investigate the adjunctive use
      of corticosteroids in such cases. TB patients with ARF requiring mechanical
      ventilation (n = 90) were enrolled retrospectively during 1989-2006. The patients
      were divided into two groups: tuberculous pneumonia (TBP; n = 66), and miliary TB
      (MTB; n = 24). The TBP patients were older than the MTB patients (mean age 68.0
      versus 54.5 yrs), and the mean+/-SD interval from hospital admission to start of
      anti-TB treatment was longer for the TBP than for the MTB group (5.0+/-7.0 versus
      2.8+/-2.5 days). However, there was no difference in in-hospital mortality rate
      between the two groups (68.2 versus 58.3%). In the TBP patients, multivariate
      analysis showed that advanced age and shock unrelated to sepsis were associated
      with poor outcomes. Even though corticosteroid use was a predictor of survival in
      TBP patients, it was difficult to conclusively determine the efficacy of
      corticosteroids in TBP with ARF because of the retrospective study design. The
      present study reveals the need for randomised controlled trials to clarify the
      role of corticosteroids as adjunctive therapy in the management of tuberculous
      pneumonia with acute respiratory failure.

PMID- 18614560
TI  - Genetic variants of microsomal epoxide hydrolase and glutamate-cysteine ligase in
      COPD.
AB  - The genetic factors that contribute to the development of chronic obstructive
      pulmonary disease (COPD) are poorly understood. Many candidate genes have been
      proposed, including enzymes that protect the lung against oxidative stress, such
      as microsomal epoxide hydrolase (EPHX1) and glutamate-cysteine ligase (GCL). To
      date, most reported findings have been for EPHX1, particularly in relation to
      functional variants associated with fast and slow metabolism of epoxide
      intermediates. The present study aimed to identify any association of variation
      in these genes with COPD susceptibility or severity. In total, 1,017 white COPD
      patients and 912 nondiseased age and sex matched smoking controls were genotyped
      for six single nucleotide polymorphisms (SNPs) in EPHX1 (including the fast and
      slow variants and associated haplotypes), and eight SNPs in the two genes
      encoding GCL. GCL is a rate-limiting enzyme in the synthesis of glutathione, a
      major contributor to anti-oxidant protection in the lung. No association of
      variation was found in EPHX1 or GCL with susceptibility to COPD or disease
      severity. This is the largest reported study to date and is well powered to
      detect associations that have been previously suggested. The current data
      indicate that these genetic variants are unlikely to be related to susceptibility
      or disease severity in white chronic obstructive pulmonary disease patients.

PMID- 18614561
TI  - GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a
      meta-analysis.
AB  - The global extensively drug-resistant tuberculosis (TB) response plan calls for
      implementation of rapid tests to screen patients at risk of drug-resistant TB.
      Currently, two line probe assays exist, the INNO-LiPA(R)Rif.TB assay
      (Innogenetics, Ghent, Belgium) and the GenoType MTBDR assay (Hain LifeScience
      GmbH, Nehren, Germany). While LiPA studies have been reviewed, the accuracy of
      GenoType assays has not been systematically reviewed. The present authors carried
      out a systematic review and used meta-analysis methods appropriate for diagnostic
      accuracy. After the literature searches, 14 comparisons for rifampicin and 15
      comparisons for isoniazid were identified in 10 articles that used GenoType MTBDR
      assays. Accuracy results were summarised in forest plots and pooled using
      bivariate random-effects regression. The pooled sensitivity (98.1%, 95%
      confidence interval (CI) 95.9-99.1) and specificity (98.7%, 95% CI 97.3-99.4)
      estimates for rifampicin resistance were very high and consistent across all
      subgroups, assay versions and specimen types. The accuracy for isoniazid was
      variable, with lower sensitivity (84.3%, 95% CI 76.6-89.8) and more inconsistent
      than specificity (99.5%, 95% CI 97.5-99.9). GenoType MDTBR assays demonstrate
      excellent accuracy for rifampicin resistance, even when used on clinical
      specimens. While specificity is excellent for isoniazid, sensitivity estimates
      were modest and variable. Together with data from demonstration projects, the
      meta-analysis provides evidence for policy making and clinical practice.

PMID- 18614562
TI  - Properties of a store-operated nonselective cation channel in airway smooth
      muscle.
AB  - Passive depletion of internal Ca(2+) stores in airway smooth muscle (ASM)
      activates nonselective cation channels (NSCCs) that mediate capacitative Ca(2+)
      entry. However, the single channel properties of these cation channels have yet
      to be resolved and their regulation by cytosolic Ca(2+) levels ([Ca(2+)](i))
      still remains unclear. NSCC currents and changes in [Ca(2+)](i) during passive
      depletion of internal Ca(2+) stores were monitored in isolated bovine tracheal
      myocytes. Loading cells with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetracetic
      acid acetyl methyl ester (BAPTA-AM) to reduce [Ca(2+)](i) and thereby deplete the
      store augmented a basal Gd(3+)- and La(3+)-sensitive, Ca(2+)-permeable NSCC
      current. This current mimics that which is evoked by store depletion using the
      sarcoplasmic reticulum Ca(2+) pump inhibitor cyclopiazonic acid (which
      concurrently and transiently elevates [Ca(2+)](i)). Both interventions activated
      an approximately 25-pS NSCC with properties identical to both spontaneous (basal)
      and BAPTA-AM-evoked single channel currents. In summary, the present study
      provides novel evidence that a lanthanide-sensitive, 25-pS nonselective cation
      channel underlies both basal and store depletion-evoked membrane currents in
      airway smooth muscle and that this conductance likely contributes to the
      regulation of resting [Ca(2+)](i) and capacitative Ca(2+) entry.

PMID- 18614563
TI  - Gene expression in CD4+ T-cells reflects heterogeneity in infant wheezing
      phenotypes.
AB  - Although a marked increase in the reporting of wheezing symptoms since the mid
      1970s has been described, the underlying immunopathology of the different
      wheezing phenotypes has not been clarified. Since differences in gene expression
      might be involved, the objective of the present study was to identify gene
      expression profiles in CD4+ T-cells from two distinct infant wheezing phenotypes.
      The gene expression profiles of peripheral CD4+ T-cells were compared by means of
      microarray analysis of six transient wheezers, six persistent wheezers and seven
      healthy controls. The differentially expressed genes were subsequently validated
      by RT-PCR. The differential gene expression profiles reflected common
      immunological pathways involved in apoptosis or proliferation of T-cells.
      Furthermore, both wheezing phenotypes showed decreased expression of the
      complement component 5 receptor 1 gene, a gene involved in the regulation of
      bronchial responsiveness. Moreover, differences in gene expression profiles were
      found in genes involved in the immune response against respiratory syncytial
      virus, such as those encoding signal transducer and activator of transcription 1
      and an inflammatory mediator showing enhanced production in asthma (prostaglandin
      E(2) receptor 2). The present findings suggest that clinical symptoms of wheeze
      are reflected in common immunological pathways, whereas differences between
      wheezing phenotypes are, in part, reflected in distinct gene expression profiles.

PMID- 18614564
TI  - Proteomics analysis identifies phosphorylation-dependent alpha-synuclein protein
      interactions.
AB  - Mutations and copy number variation in the SNCA gene encoding the neuronal
      protein alpha-synuclein have been linked to familial Parkinson disease (Thomas,
      B., and Beal, M. F. (2007) Parkinson's disease. Hum. Mol. Genet. 16, R183-R194).
      The carboxyl terminus of alpha-synuclein can be phosphorylated at tyrosine 125
      and serine 129, although only a small fraction of the protein is phosphorylated
      under normal conditions (Okochi, M., Walter, J., Koyama, A., Nakajo, S., Baba,
      M., Iwatsubo, T., Meijer, L., Kahle, P. J., and Haass, C. (2000) Constitutive
      phosphorylation of the Parkinson's disease associated alpha-synuclein. J. Biol.
      Chem. 275, 390-397). Under pathological conditions, such as in Parkinson disease,
      alpha-synuclein is a major component of Lewy bodies, a pathological hallmark of
      Parkinson disease, and is mostly phosphorylated at Ser-129 (Anderson, J. P.,
      Walker, D. E., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J.,
      Barbour, R., Huang, J. P., Kling, K., Lee, M., Diep, L., Keim, P. S., Shen, X.
      F., Chataway, T., Schlossmacher, M. G., Seubert, P., Schenk, D., Sinha, S., Gai,
      W. P., and Chilcote, T. J. (2006) Phosphorylation of Ser-129 is the dominant
      pathological modification of alpha-synuclein in familial and sporadic Lewy body
      disease. J. Biol. Chem. 281, 29739-29752). Controversy exists over the extent to
      which phosphorylation of alpha-synuclein and/or the visible protein aggregation
      in Lewy bodies are steps in disease pathogenesis, are protective, or are neutral
      markers for the disease process. Here we used the combination of peptide pulldown
      assays and mass spectrometry to identify and compare protein-protein interactions
      of phosphorylated and non-phosphorylated alpha-synuclein. We showed that non
      phosphorylated alpha-synuclein carboxyl terminus pulled down protein complexes
      that were highly enriched for mitochondrial electron transport proteins, whereas
      alpha-synuclein carboxyl terminus phosphorylated on either Ser-129 or Tyr-125 did
      not. Instead the set of proteins pulled down by phosphorylated alpha-synuclein
      was highly enriched in certain cytoskeletal proteins, in vesicular trafficking
      proteins, and in a small number of enzymes involved in protein serine
      phosphorylation. This targeted comparative proteomics approach for unbiased
      identification of protein-protein interactions suggests that there are functional
      consequences when alpha-synuclein is phosphorylated.

PMID- 18614565
TI  - Extensive analysis of the cytoplasmic proteome of human erythrocytes using the
      peptide ligand library technology and advanced mass spectrometry.
AB  - The erythrocyte cytoplasmic proteome is composed of 98% hemoglobin; the remaining
      2% is largely unexplored. Here we used a combinatorial library of hexameric
      peptides as a capturing agent to lower the signal of hemoglobin and amplify the
      signal of low to very low abundance proteins in the cytoplasm of human red blood
      cells (RBCs). Two types of hexapeptide library beads have been adopted: amino
      terminal hexapeptide beads and beads in which the peptides have been further
      derivatized by carboxylation. The amplification of the signal of low abundance
      and suppression of the signal of high abundance species were fully demonstrated
      by two-dimensional gel maps and nano-LC-MSMS analysis. The effect of this new
      methodology on quantitative information also was explored. Moreover using this
      approach on an LTQ-Orbitrap mass spectrometer, we could identify with high
      confidence as many as 1578 proteins in the cytoplasmic fraction of a highly
      purified preparation of RBCs, allowing a deep exploration of the classical RBC
      pathways as well as the identification of unexpected minor proteins. In addition,
      we were able to detect the presence of eight different hemoglobin chains
      including embryonic and newly discovered globin chains. Thus, this extensive
      study provides a huge data set of proteins that are present in the RBC cytoplasm
      that may help to better understand the biology of this simplified cell and may
      open the way to further studies on blood pathologies using targeted approaches.

PMID- 18614566
TI  - Outcomes of 23- and 25-gauge transconjunctival sutureless vitrectomies for
      idiopathic macular holes.
AB  - BACKGROUND/AIMS: To assess the outcomes of 23-gauge sutureless transconjunctival
      vitrectomies (TSV), as compared with 25-gauge TSV in macular hole surgeries.
      METHODS: A retrospective, consecutive, interventional case series of 47 eyes with
      idiopathic macular holes treated by 23- or 25-gauge TSV were analysed. RESULTS:
      The operative time was 37.2 (SD 8.9) min with 23-gauge TSV and 34.2 (8.7) min
      with 25-gauge TSV (p = 0.388). The anatomical success rate was 96% with 23-gauge
      TSV and 92% with 25-gauge TSV (p>0.999). The logarithm of the minimum angle of
      resolution of best-corrected visual acuity (BCVA) at the sixth postoperative
      month was 0.19 (0.16) with 23-gauge TSV and 0.19 (0.25) with 25-gauge TSV (p =
      0.521). Postoperative improvement in BCVA was comparable between the two TSVs.
      IOP on postoperative day 1 was lower with 25-gauge TSV (12.3 (4.9) mm Hg) than
      with 23-gauge TSV (17.4 (5.8) mm Hg) (p = 0.036). Complications included retinal
      break, intraoperative bleeding and slippage of the infusion cannula with 23-gauge
      TSV, while retinal detachment and postoperative hypotony occurred in the 25-gauge
      TSV group (p = 0.570). CONCLUSION: 23-gauge TSV appears to be as safe and
      effective as 25-gauge TSV in macular hole surgery.

PMID- 18614567
TI  - Correlation of spectral optical coherence tomography with fluorescein and
      indocyanine green angiography in multiple evanescent white dot syndrome.
AB  - AIMS: To determine the spatial location of lesions in multiple evanescent white
      dot syndrome (MEWDS) with the aid of spectral optical coherence topography
      (SOCT), fluorescein angiography (FA) and indocyanine green angiography (ICGA).
      METHODS: A novel method of three-dimensional SOCT data analysis called
      reflectivity maps was introduced. The reflectivity maps display the distribution
      of a back-reflected intensity taken only from individual retinal layers located
      at specific distance from the reference plane. Reflectivity maps of the inner
      retina, the junction between photoreceptor inner and outer segments (IS/OS),
      retinal pigment epithelium and choroid of the patient with MEWDS were created and
      correlated with FA and ICGA. RESULTS: During the acute stage of MEWDS, the
      reflectivity map of the IS/OS junction displayed areas of reduced reflectivity
      that showed a strong positive correlation with hypofluorescent ICGA spots and a
      weaker but positive correlation with hyperfluorescent FA dots. SOCT examination
      did not reveal any pathological changes involving either any other retinal layers
      or the inner choroid. CONCLUSION: Disseminated disruptions of the IS/OS junction
      seen on SOCT cross-sectional images in the acute stage of MEWDS form the pattern
      of spots that can be correlated with those revealed by ICGA. This suggests that
      hypofluorescent ICGA spots indicate alternations in the retinal pigment
      epithelium-photoreceptor complex and do not represent inflammatory choroidal
      lesions.

PMID- 18614568
TI  - Vision screening for frail older people: a randomised trial.
AB  - AIM: To assess the effects of vision screening, and subsequent management of
      visual impairment, on visual acuity and vision-related quality of life among
      frail older people. DESIGN: Randomised controlled trial. SETTING: Community in
      Sydney, Australia. PARTICIPANTS: 616 men and women aged 70 years and over (mean
      age 81 years) recruited mainly from people attending outpatient aged care
      services. CONTROL: No vision assessment or intervention INTERVENTIONS:
      Comprehensive vision and eye examinations conducted by an optometrist. Three
      hundred subjects were seen by the study optometrist, with 146 judged to need
      treatment for a vision or eye problem. The optometrist arranged new glasses for
      92 subjects; 24 were referred for a home visit by an occupational therapist; 17
      were referred for glaucoma management; and 15 were referred for cataract surgery.
      MAIN OUTCOME MEASURE: Distance and near visual acuity (logMAR) and composite
      scores on the 25-item version of the National Eye Institute Visual Function
      Questionnaire, both assessed at a 12-month follow-up home visit. RESULTS: After
      12 months' follow-up, the mean (logMAR) distance visual acuity was 0.27 in the
      intervention group and 0.25 in the control group (p = 0.32). The mean (logMAR)
      near visual acuities were -0.01 in the intervention group and -0.03 in the
      control group (p = 0.26). The mean composite score on the National Eye Institute
      Visual Function Questionnaire was 84.3 in the intervention group and 86.4 in the
      control group (p = 0.49). CONCLUSIONS: Vision screening by an optometrist for
      frail older people living in the community in Australia does not lead to
      improvements in vision or vision-related quality of life after 1 year's follow
      up.

PMID- 18614569
TI  - Retinal microvascular abnormalities and cognitive dysfunction: a systematic
      review.
AB  - OBJECTIVE: To examine the evidence for an association between cognitive
      impairment or dementia and the presence of retinal microvascular abnormalities.
      METHODS: A systematic review of observational studies identified through
      searching five electronic databases and reference lists. Studies were required to
      have both a recognised cognitive function assessment (either a structured
      neuropsychological test or a clinical evaluation of dementia), and assessment of
      the retinal microvasculature (either characteristics associated with generalised
      retinopathy or changes specific to arterioles or venules). RESULTS: 6 studies
      were included. Studies were clinically and methodologically heterogeneous and of
      variable quality. Some degree of cognitive impairment was found to be associated
      with the presence of retinal microvascular abnormalities in all studies, although
      the extent of the association varied. The presence of retinal vascular signs was
      mostly associated with poorer verbal memory, mental speed and executive function
      in the general population, but not consistently associated with other cognitive
      modalities. CONCLUSIONS: There is some evidence suggesting a positive association
      between retinal microvascular abnormalities and cognitive impairment or dementia
      in elderly people and in patients with diabetes. Findings are inconclusive, and
      further better designed studies are required, with standardised and objective
      retinal vascular assessment and a range of sensitive cognitive tests.

PMID- 18614570
TI  - Pegaptanib sodium for neovascular age-related macular degeneration: third-year
      safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION)
      trial.
AB  - AIMS: To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the
      treatment of neovascular age-related macular degeneration (NV-AMD). METHODS: Two
      concurrent, prospective, multicentre, double-masked studies randomised subjects
      with all angiographic lesion compositions of NV-AMD to receive intravitreous
      pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54
      weeks. Those initially assigned to pegaptanib were rerandomised to continue or
      discontinue therapy for 48 more weeks; sham-treated subjects continued sham,
      discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib
      0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who
      did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg
      for year 3. RESULTS: As in years 1 and 2, pegaptanib was well tolerated in year
      3. Adverse events were mainly ocular in nature, mild, transient and injection
      related. Serious adverse events were rare. No evidence of systemic safety signals
      attributed to vascular endothelial growth factor inhibition arose in year 3.
      There were no findings in relation to vital signs or electrocardiogram results
      suggesting a relationship to pegaptanib treatment. CONCLUSION: The 3-year safety
      profile of pegaptanib sodium was favourable in patients with NV-AMD.

PMID- 18614571
TI  - Development of distant stereoacuity in visually normal children as measured by
      the Frisby-Davis distance stereotest.
AB  - AIMS: To establish the range of normal distance stereoacuity and evaluate its
      development in visually normal children by using the Frisby-Davis distance
      stereotest (FD2). METHODS: The distance stereoacuity of visually normal children
      aged less than 11 years and of adults was measured with FD2 using a standard
      testing protocol. RESULT: This study involved 94 visually normal children aged 36
      131 months and 46 visually normal adults aged 20-49 years. The distance
      stereoacuity of the children aged 36-59 months was 40.61 (SD 9.823) seconds of
      arc; that of the children aged 60-119 months, 14.18 (8.152) seconds of arc; and
      that of the adults, 12.50 (4.802) seconds of arc. The FD2 distance stereoacuity
      of the children aged 36-59 months differed significantly from that of the older
      subjects (p = 0.000), and the FD2 distance stereoacuity of the children aged more
      than 59 months did not differ significantly from that of the adults (p = 0.813).
      CONCLUSION: Distance stereoacuity reaches adult levels at approximately 5 years
      of age. These data of the age-related normal values could represent a reference
      frame for the comparison of data obtained for clinical populations.

PMID- 18614572
TI  - Tuberculous orbital apex syndromes.
AB  - AIMS: To describe the clinical and radiological features of orbital apex
      syndromes caused by presumed tuberculosis (TB). METHODS: A review of the
      discharge summaries of all patients seen in the Medical Eye Unit (MEU), St
      Thomas' Hospital between 1975 and 2006 identified seven patients with a diagnosis
      of orbital apex syndrome or optic neuropathy attributable to TB. Case notes and
      radiology were reviewed retrospectively for each patient. RESULTS: All of the
      patients were born outside the UK and were HIV-negative. Four presented during
      2005-6. Six of the seven patients presented with a visual acuity (VA) of less
      than counting fingers (CF), but all achieved a VA of 6/9 or better after a median
      3 weeks of treatment with antituberculous treatment and systemic corticosteroids.
      All patients had constitutional symptoms. Chest x ray and CSF were normal in each
      case, but MRI was abnormal in six. CONCLUSIONS: We report a recent cluster of
      tuberculous orbital apex syndromes, in the context of an increasing incidence of
      TB in the UK. The condition is difficult to diagnose, but the combination of high
      dose corticosteroids and anti-TB medication was rapidly effective and achieved a
      good outcome in all cases.

PMID- 18614573
TI  - Retinal nerve fibre layer thickness measurements using optical coherence
      tomography in migraine patients.
AB  - AIM: To compare the retinal nerve fibre layer (RNFL) thickness in eyes of
      migraine patients with age-matched healthy subjects using optical coherence
      tomography. METHODS: The study was designed as an observational cross-sectional
      study. 70 eyes of 70 patients (mean age 28.2 (SD 7.9) years) with migraine with
      or without aura according to the criteria of the Headache International Society
      and 53 eyes of 53 age-matched healthy controls (mean age 28.0 (8.1) years) were
      included. Optical coherence tomography was performed with the Stratus OCT (model
      3000, software ver. 4.0.2; Carl Zeiss Meditec, Dublin, CA) after pupillary
      dilation. The fast RNFL thickness (3.4) scan acquisition protocol was used.
      RESULTS: In the migraine group, the mean Migraine Disability Assessment Score
      (MIDAS), the mean number of attacks per 3 months, and the length of migraine
      history were 34.3 (15.2), 17.0 (6.7) and 14.8 (5.6), respectively. The RNFL
      average thickness in the migraine was within the normal range, but the temporal
      quadrant RNFL thickness in the migraine patients was significantly lower than
      that of the control group, 62.2 (10.8) mum vs 70.8 (12.4) mum, respectively (p =
      0.0001). However, there was no difference between migraineurs and controls in the
      superior, inferior, and nasal quadrants, p = 0.8810, p = 0.1531, and p = 0.8300,
      respectively. Within the migraine group, the average RNFL thickness was
      significantly correlated with the MIDAS disability score (r = -0.93, p<0.0001)
      and the frequency of migraine attacks (r = -0.86, p<0.0001). There were no
      statistically significant differences, between study groups, in disc area or
      cup/disc area ratio, p = 0.8102 and p = 0.7236, respectively. Considering the
      clinical examination, RNFL, and optic disc parameters, no one in the migraine
      group was qualified as having glaucomatous damage. CONCLUSION: The RNFL in the
      temporal quadrant was found to be thinner in migraine patients. In addition, we
      found a strong correlation between migraine severity and the RNFL average
      thickness parameters.

PMID- 18614574
TI  - Foveal contrast processing of increment and decrement targets is equivalently
      reduced in glaucoma.
AB  - BACKGROUND: Psychophysical measurement of the function of individual precortical
      visual pathways (magnocellular, parvocellular and koniocellular) has enabled the
      development of sensitive tests for glaucoma and has enhanced understanding of its
      pathophysiology. Such pathways can be further subdivided into their "On" and
      "Off" components, which have anatomical and physiological asymmetries. This study
      investigated whether On and Off subdivisions of the magnocellular (M) pathway are
      differentially affected by glaucoma. METHODS: 20 participants with glaucoma and
      20 controls underwent two psychophysical procedures that have been shown to
      assess the M pathway (steady pedestal task) and its On and Off subdivisions
      (pedestal-delta-pedestal task) respectively. Luminance discrimination thresholds
      were measured foveally, using both increment and decrement stimuli. RESULTS: The
      steady pedestal (undifferentiated M-pathway) task separated the glaucoma and
      control groups (p = 0.04) with equivalent outcomes for increment and decrement
      targets. The pedestal-delta-pedestal task (isolated On and Off M-pathway
      subdivisions) also differentiated between groups (p = 0.025), but the outcome was
      not dependent on which subdivision was isolated. CONCLUSIONS: This study found
      that increment and decrement targets can be used with equal effectiveness for
      detecting contrast processing deficits in early glaucoma. Outcomes further
      suggested that glaucoma affects On and Off subdivisions of the M-pathway
      equivalently.

PMID- 18614575
TI  - Maternal depletion of CTCF reveals multiple functions during oocyte and
      preimplantation embryo development.
AB  - CTCF is a multifunctional nuclear factor involved in epigenetic regulation.
      Despite recent advances that include the systematic discovery of CTCF-binding
      sites throughout the mammalian genome, the in vivo roles of CTCF in adult tissues
      and during embryonic development are largely unknown. Using transgenic RNAi, we
      depleted maternal stores of CTCF from growing mouse oocytes, and identified
      hundreds of misregulated genes. Moreover, our analysis suggests that CTCF
      predominantly activates or derepresses transcription in oocytes. CTCF depletion
      causes meiotic defects in the egg, and mitotic defects in the embryo that are
      accompanied by defects in zygotic gene expression, and culminate in apoptosis.
      Maternal pronuclear transfer and CTCF mRNA microinjection experiments indicate
      that CTCF is a mammalian maternal effect gene, and that persistent
      transcriptional defects rather than persistent chromosomal defects perturb early
      embryonic development. This is the first study detailing a global and essential
      role for CTCF in mouse oocytes and preimplantation embryos.

PMID- 18614577
TI  - The Ecdysone-inducible zinc-finger transcription factor Crol regulates Wg
      transcription and cell cycle progression in Drosophila.
AB  - The steroid hormone Ecdysone is crucial for developmental cell death,
      proliferation and morphogenesis in Drosophila. Herein, we delineate a molecular
      pathway linking Ecdysone signalling to cell cycle regulation in the Drosophila
      developing wing. We present evidence that the Ecdysone-inducible zinc-finger
      transcription factor Crol provides a crucial link between the Ecdysone steroid
      hormone pathway and the Wingless (Wg) signalling pathway in Drosophila. We
      identified Crol as a strong enhancer of a wing phenotype generated by
      overexpression of the Wg-inducible cell cycle inhibitor Hfp. We demonstrate that
      Crol is required for cell cycle progression: crol mutant clones have reduced cell
      cycles and are removed by apoptosis, while upregulation of Crol overrides the Wg
      mediated developmental cell cycle arrest in the zone of non-proliferating cells
      in the wing disc. Furthermore, we show that Crol acts to repress wg
      transcription. We also show that overexpression of crol results in downregulation
      of Hfp, consistent with the identification of the crol mutant as a dominant
      enhancer of the Hfp overexpression phenotype. Taken together, our studies have
      revealed a novel mechanism for cell cycle regulation, whereby Crol links steroid
      hormone signals to Wg signalling and the regulation of crucial cell cycle
      targets.

PMID- 18614576
TI  - Dap160/intersectin binds and activates aPKC to regulate cell polarity and cell
      cycle progression.
AB  - The atypical protein kinase C (aPKC) is required for cell polarization of many
      cell types, and is upregulated in several human tumors. Despite its importance in
      cell polarity and growth control, relatively little is known about how aPKC
      activity is regulated. Here, we use a biochemical approach to identify Dynamin
      associated protein 160 (Dap160; related to mammalian intersectin) as an aPKC
      interacting protein in Drosophila. We show that Dap160 directly interacts with
      aPKC, stimulates aPKC activity in vitro and colocalizes with aPKC at the apical
      cortex of embryonic neuroblasts. In dap160 mutants, aPKC is delocalized from the
      neuroblast apical cortex and has reduced activity, based on its inability to
      displace known target proteins from the basal cortex. Both dap160 and aPKC
      mutants have fewer proliferating neuroblasts and a prolonged neuroblast cell
      cycle. We conclude that Dap160 positively regulates aPKC activity and
      localization to promote neuroblast cell polarity and cell cycle progression.

PMID- 18614578
TI  - Hedgehog and Wingless stabilize but do not induce cell fate during Drosophila
      dorsal embryonic epidermal patterning.
AB  - A fundamental concept in development is that secreted molecules such as Wingless
      (Wg) and Hedgehog (Hh) generate pattern by inducing cell fate. By following
      markers of cellular identity posterior to the Wg- and Hh-expressing cells in the
      Drosophila dorsal embryonic epidermis, we provide evidence that neither Wg nor Hh
      specifies the identity of the cell types they pattern. Rather, they maintain pre
      existing cellular identities that are otherwise unstable and progress stepwise
      towards a default fate. Wg and Hh therefore generate pattern by inhibiting
      specific switches in cell identity, showing that the specification and the
      patterning of a given cell are uncoupled. Sequential binary decisions without
      induction of cell identity give rise to both the groove cells and their posterior
      neighbors. The combination of independent progression of cell identity and arrest
      of progression by signals facilitates accurate patterning of an extremely plastic
      developing epidermis.

PMID- 18614579
TI  - Hedgehog signaling is involved in development of the neocortex.
AB  - Sonic hedgehog (Shh) function is essential for patterning and cell fate
      specification, particularly in ventral regions of the central nervous system. It
      is also a crucial mitogen for cerebellar granule neuron precursors and is
      important in maintenance of the stem cell niche in the postnatal telencephalon.
      Although it has been reported that Shh is expressed in the developing dorsal
      telencephalon, functions of Shh in this region are unclear, and detailed
      characterization of Shh mRNA transcripts in situ has not been demonstrated. To
      clarify the roles of Shh signaling in dorsal pallium (neocortex primordium)
      development, we have knocked out the Shh and Smo genes specifically in the early
      developing dorsal telencephalon by using Emx1cre mice. The mutants showed a
      smaller dorsal telencephalon at E18.5, which was caused by cell cycle kinetics
      defects of the neural progenitor/stem cells. The cell cycle length of the
      progenitor/stem cells was prolonged, and the number of cycle-exiting cells and
      neurogenesis were decreased. Birth-date analysis revealed abnormal positioning of
      neurons in the mutants. The characteristics of the subventricular zone,
      ventricular zone and subplate cells were also affected. Weak immunoreactivity of
      Shh was detected in the dorsal telencephalon of wild types. Reduced Shh
      immunoreactivity in mutant dorsal telencephalons supports the above phenotypes.
      Our data indicate that Shh signaling plays an important role in development of
      the neocortex.

PMID- 18614580
TI  - The C. elegans F-spondin family protein SPON-1 maintains cell adhesion in neural
      and non-neural tissues.
AB  - The F-spondin family of extracellular matrix proteins has been implicated in axon
      outgrowth, fasciculation and neuronal cell migration, as well as in the
      differentiation and proliferation of non-neuronal cells. In screens for mutants
      defective in C. elegans embryonic morphogenesis, we identified SPON-1, the only
      C. elegans member of the spondin family. SPON-1 is synthesized in body muscles
      and localizes to integrin-containing structures on body muscles and to other
      basement membranes. SPON-1 maintains strong attachments of muscles to epidermis;
      in the absence of SPON-1, muscles progressively detach from the epidermis,
      causing defective epidermal elongation. In animals with reduced integrin
      function, SPON-1 becomes dose dependent, suggesting that SPON-1 and integrins
      function in concert to promote the attachment of muscles to the basement
      membrane. Although spon-1 mutants display largely normal neurite outgrowth, spon
      1 synergizes with outgrowth defective mutants, revealing a cryptic role for SPON
      1 in axon extension. In motoneurons, SPON-1 acts in axon guidance and
      fasciculation, whereas in interneurons SPON-1 maintains process position. Our
      results show that a spondin maintains cell-matrix adhesion in multiple tissues.

PMID- 18614581
TI  - Identification of a tumor-initiating stem cell population in human renal
      carcinomas.
AB  - The purpose of the present study was to search for the presence of a tumor
      initiating stem cell population in renal carcinomas. Based on the recent
      identification of mesenchymal stem cells in normal kidneys, we sorted cells
      expressing the mesenchymal stem cell marker CD105 from 5 human renal carcinomas.
      Because the CD105(+) but not the CD105(-) population showed enhanced
      tumorigenicity when injected in severely compromised immunodeficient (SCID) mice,
      we cloned and characterized CD105(+) cells and evaluated their stemness,
      differentiative ability, and serial tumor generation. Characterization of the
      phenotype of CD105(+) clones revealed several stem cell properties: 1) clonogenic
      ability, 2) expression of nestin, Nanog, Oct4 stem cell markers, and lack of
      differentiative epithelial markers, 3) ability to grow in nonadhesive spheroids,
      4) in vitro differentiation into epithelial and endothelial cell types, and 5)
      generation in vivo of serially transplantable carcinomas containing an
      undifferentiated CD105(+) tumorigenic and a differentiated CD105(-)
      nontumorigenic population. In addition, some vessels present in carcinomas
      generated from CD105(+) clones were of human origin, suggesting the capability of
      tumor-initiating stem cells to in vivo differentiate also in endothelial cells.
      In conclusion, we demonstrate that CD105(+) cells and clones derived from renal
      carcinomas were enriched in tumor-initiating cells with stem characteristics.

PMID- 18614583
TI  - Dynamical modeling and multi-experiment fitting with PottersWheel.
AB  - MOTIVATION: Modelers in Systems Biology need a flexible framework that allows
      them to easily create new dynamic models, investigate their properties and fit
      several experimental datasets simultaneously. Multi-experiment-fitting is a
      powerful approach to estimate parameter values, to check the validity of a given
      model, and to discriminate competing model hypotheses. It requires high
      performance integration of ordinary differential equations and robust
      optimization. RESULTS: We here present the comprehensive modeling framework
      Potters-Wheel (PW) including novel functionalities to satisfy these requirements
      with strong emphasis on the inverse problem, i.e. data-based modeling of
      partially observed and noisy systems like signal transduction pathways and
      metabolic networks. PW is designed as a MATLAB toolbox and includes numerous user
      interfaces. Deterministic and stochastic optimization routines are combined by
      fitting in logarithmic parameter space allowing for robust parameter calibration.
      Model investigation includes statistical tests for model-data-compliance, model
      discrimination, identifiability analysis and calculation of Hessian- and Monte
      Carlo-based parameter confidence limits. A rich application programming interface
      is available for customization within own MATLAB code. Within an extensive
      performance analysis, we identified and significantly improved an integrator
      optimizer pair which decreases the fitting duration for a realistic benchmark
      model by a factor over 3000 compared to MATLAB with optimization toolbox.
      AVAILABILITY: PottersWheel is freely available for academic usage at
      http://www.PottersWheel.de/. The website contains a detailed documentation and
      introductory videos. The program has been intensively used since 2005 on Windows,
      Linux and Macintosh computers and does not require special MATLAB toolboxes.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 18614582
TI  - Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA
      binding, oligomerization, and vaccine design.
AB  - The threat of a pandemic outbreak of influenza virus A H5N1 has become a major
      concern worldwide. The nucleoprotein (NP) of the virus binds the RNA genome and
      acts as a key adaptor between the virus and the host cell. It, therefore, plays
      an important structural and functional role and represents an attractive drug
      target. Here, we report the 3.3-A crystal structure of H5N1 NP, which is composed
      of a head domain, a body domain, and a tail loop. Our structure resolves the
      important linker segments (residues 397-401, 429-437) that connect the tail loop
      with the remainder of the molecule and a flexible, basic loop (residues 73-91)
      located in an arginine-rich groove surrounding Arg150. Using surface plasmon
      resonance, we found the basic loop and arginine-rich groove, but mostly a
      protruding element containing Arg174 and Arg175, to be important in RNA binding
      by NP. We also used our crystal structure to build a ring-shaped assembly of nine
      NP subunits to model the miniribonucleoprotein particle previously visualized by
      electron microscopy. Our study of H5N1 NP provides insight into the
      oligomerization interface and the RNA-binding groove, which are attractive drug
      targets, and it identifies the epitopes that might be used for universal vaccine
      development.

PMID- 18614584
TI  - Yale Image Finder (YIF): a new search engine for retrieving biomedical images.
AB  - Yale Image Finder (YIF) is a publicly accessible search engine featuring a new
      way of retrieving biomedical images and associated papers based on the text
      carried inside the images. Image queries can also be issued against the image
      caption, as well as words in the associated paper abstract and title. A typical
      search scenario using YIF is as follows: a user provides few search keywords and
      the most relevant images are returned and presented in the form of thumbnails.
      Users can click on the image of interest to retrieve the high resolution image.
      In addition, the search engine will provide two types of related images: those
      that appear in the same paper, and those from other papers with similar image
      content. Retrieved images link back to their source papers, allowing users to
      find related papers starting with an image of interest. Currently, YIF has
      indexed over 140 000 images from over 34 000 open access biomedical journal
      papers. AVAILABILITY: http://krauthammerlab.med.yale.edu/imagefinder/

PMID- 18614585
TI  - Synchronous versus asynchronous modeling of gene regulatory networks.
AB  - MOTIVATION: In silico modeling of gene regulatory networks has gained some
      momentum recently due to increased interest in analyzing the dynamics of
      biological systems. This has been further facilitated by the increasing
      availability of experimental data on gene-gene, protein-protein and gene-protein
      interactions. The two dynamical properties that are often experimentally testable
      are perturbations and stable steady states. Although a lot of work has been done
      on the identification of steady states, not much work has been reported on in
      silico modeling of cellular differentiation processes. RESULTS: In this
      manuscript, we provide algorithms based on reduced ordered binary decision
      diagrams (ROBDDs) for Boolean modeling of gene regulatory networks. Algorithms
      for synchronous and asynchronous transition models have been proposed and their
      corresponding computational properties have been analyzed. These algorithms allow
      users to compute cyclic attractors of large networks that are currently not
      feasible using existing software. Hereby we provide a framework to analyze the
      effect of multiple gene perturbation protocols, and their effect on cell
      differentiation processes. These algorithms were validated on the T-helper model
      showing the correct steady state identification and Th1-Th2 cellular
      differentiation process. AVAILABILITY: The software binaries for Windows and
      Linux platforms can be downloaded from http://si2.epfl.ch/~garg/genysis.html.

PMID- 18614586
TI  - Is there an optimal chemotherapy regimen for the treatment of advanced gastric
      cancer that will provide a platform for the introduction of new biological
      agents?
AB  - Globally, gastric cancer is the second most common cause of cancer-related death.
      The majority of gastric cancer patients will have at presentation or will
      ultimately develop overt metastatic disease. Meta-analysis has demonstrated not
      only that systemic chemotherapy can improve survival in patients with advanced
      disease but also that the best survival results in earlier randomized studies
      have been achieved with three-drug regimens containing a fluoropyrimidine, an
      anthracycline, and cisplatin. Although there has been little progress
      historically in improving median overall survival times beyond the 9-month
      plateau achievable with the standard epirubicin-cisplatin-infusional 5
      fluoropyrimidine (ECF) combination, the availability of newer cytotoxic
      anticancer agents has provided some measure of optimism that current outcomes can
      be improved. A number of new triplet and doublet combinations incorporating
      docetaxel, oxaliplatin, irinotecan, capecitabine, and S-1 have been explored in
      randomized trials. Although some combinations, such as epirubicin-oxaliplatin
      capecitabine, have been shown to be as effective as (or perhaps more effective
      than) ECF, and although promising early data have been derived for S-1 in
      combination with cisplatin, a lack of studies in which direct comparisons have
      been made currently hinders the identification of the optimal regimen in this
      setting. One factor that might contribute to the lack of clear progress is the
      absence of consensus on the utility of second-line cytotoxic treatments. It can
      therefore be concluded that, although there is no first-line regimen that is
      clearly the most appropriate platform for the investigation of biological agents,
      there are a number of combinations that have been shown to be effective and
      therefore good candidates.

PMID- 18614587
TI  - Central nervous system metastases in HER-2-overexpressing metastatic breast
      cancer: a treatment challenge.
AB  - With improvements in diagnostic and therapeutic options and a corresponding
      improvement in survival, central nervous system (CNS) metastasis is becoming a
      more frequent diagnosis in breast cancer patients. It can be assumed that up to
      30% of metastatic breast cancer (MBC) patients may experience CNS metastasis
      during the course of their disease. Moreover, it has been reported that patients
      with human epidermal growth factor receptor (HER)-2-overexpressing MBC are at a
      higher risk for CNS involvement. Whereas locoregional treatment modalities such
      as surgery, radiosurgery, and whole-brain radiotherapy still must be considered
      as the treatment of first choice, the armamentarium of systemic treatment
      modalities has been expanded by the introduction of small molecules such as the
      tyrosine kinase inhibitors. Rather than analyzing the risk factors for the
      development of CNS metastasis and reviewing the standard diagnostic and
      therapeutic approaches in patients with CNS involvement, this review focuses
      specifically on systemic treatment modalities in patients suffering from CNS
      metastasis from HER-2-overexpressing MBC.

PMID- 18614588
TI  - Gemcitabine pulmonary toxicity in ovarian cancer.
AB  - BACKGROUND: A case of gemcitabine-induced lung toxicity is reported in a woman
      with stage IIIc ovarian papillary serous carcinoma. CASE: An 83-year-old woman
      with stage IIIc ovarian serous papillary carcinoma diagnosed in 2001 underwent
      suboptimal cytoreductive surgery followed by carboplatin-paclitaxel chemotherapy.
      Initially in remission following chemotherapy, the disease subsequently
      progressed over the next 5 years. The patient received gemcitabine palliative
      chemotherapy. She developed significant pulmonary toxicity consistent with drug
      induced interstitial pneumonitis, which improved with steroid therapy.
      CONCLUSION: Gemcitabine, a second-line chemotherapy agent for the treatment of
      ovarian cancer, may rarely cause a serious or even fatal condition of pulmonary
      lung toxicity.

PMID- 18614589
TI  - Evaluation of vitamin D deficiency in breast cancer patients on bisphosphonates.
AB  - BACKGROUND: Bisphosphonates are very effective in treating osteoporosis and
      metastatic bone disease; however, unfavorable outcomes can occur when they are
      given to patients with occult vitamin D deficiency. No clear consensus exists on
      the assessment of vitamin D status in cancer patients undergoing bisphosphonate
      therapy. This study examines the prevalence of vitamin D deficiency among breast
      cancer patients treated with bisphosphonates for osteoporosis or metastatic bone
      disease, and observes the use of calcium and vitamin D supplementation in these
      patients. METHODS: This retrospective study reviewed the electronic records of
      321 breast cancer patients treated with bisphosphonates. Information on age,
      race, and serum levels of 25-hydroxyvitamin D (25-OHD), parathyroid hormone, and
      calcium were collected, and intakes of calcium and vitamin D supplements were
      queried in an outpatient pharmacy database. RESULTS: Of the 321 patients treated
      with bisphosphonates, 209 (65.1%) had their 25-OHD levels checked at least once.
      Of these patients, 57 (27.3%) had a serum 25-OHD level <20 ng/ml. Of the 209
      patients with a known 25-OHD level, only eight (3.8%) received >600 IU of vitamin
      D per day, and 41 (19.6%) patients received 400-600 IU of vitamin D daily.
      CONCLUSION: Especially in the setting of metastatic bone disease in breast cancer
      patients, we advocate routine 25-OHD concentration screening for vitamin D
      deficiency in general. Clear guidelines for the diagnosis of vitamin D deficiency
      in cancer patients would be extremely beneficial to have, as would identification
      of the proper dose of vitamin D supplementation. We recommend 1,000 IU daily to
      our metastatic cancer patients.

PMID- 18614590
TI  - Malignancy after solid organ transplantation: an overview.
AB  - With improving survival following solid organ transplantation, clinicians must be
      aware of post-transplant complications. One increasingly frequent complication is
      the development of malignancy after transplantation. The most common malignancies
      encountered in the post-solid organ transplant setting are nonmelanoma skin
      cancers, post-transplant lymphoproliferative disorders, and Kaposi's sarcoma
      (KS). The pathogenesis of these tumors is likely related to the immunosuppressive
      drugs used post-transplantation and subsequent viral infection. Treatment
      involves modification of the immunosuppressive drug regimen, resection of
      localized disease, and chemotherapy. We present the second reported case of a
      patient with lung transplantation who developed KS in the lung graft.

PMID- 18614591
TI  - The CYP19 TTTA repeat polymorphism is related to the prognosis of premenopausal
      stage I-II and operable stage III breast cancers.
AB  - PURPOSE: Given the critical role of the CYP19 gene, encoding aromatase, in
      estrogen synthesis and the association of the estrogen level with its TTTA repeat
      polymorphism, the potential influence of this polymorphism on breast cancer
      survival, and hence management, deserves further study. METHODS: Genotyping for
      the CYP19 TTTA repeat polymorphism was performed on 482 stage I-II and operable
      stage III Taiwanese breast cancer patients. Patients with more than seven TTTA
      repeats in either allele of CYP19 were defined as having the long allele. We
      correlated clinical variables and CYP19 genotypic polymorphism with outcome.
      RESULTS: In hormone receptor (HR)-positive breast cancers, premenopausal patients
      with the long allele of the CYP19 polymorphism had a significantly higher overall
      survival (OS) rate (8-year, 89% versus 68%; p= .003) than those without it. This
      difference was further demonstrated by a multivariate analysis (OS hazard ratio,
      1.53; p= .041). In postmenopausal women or patients with HR-negative breast
      cancer, there was no significant difference in OS between patients with or
      without the long allele. In premenopausal women with HR-positive cancers,
      adequate intensity adjuvant chemotherapy did not achieve a greater OS rate than
      suboptimal chemotherapy in patients with the long allele, but it resulted in a
      significantly higher OS rate (p= .011) than suboptimal chemotherapy in women
      without the long allele. CONCLUSIONS: The CYP19 TTTA repeat polymorphism is
      associated with survival in premenopausal women, but not in postmenopausal women,
      with HR-positive breast cancers. Premenopausal women with the long allele have a
      greater survival rate and may not gain benefit from adjuvant chemotherapy.

PMID- 18614593
TI  - A novel mutation in the SLC19A2 gene in a Turkish female with thiamine-responsive
      megaloblastic anemia syndrome.
AB  - Reported here is a 2-year-old girl who was diagnosed to have thiamine-responsive
      megaloblastic anemia during evaluations for her bilateral neurosensorial
      deafness. Besides reporting a new mutation on the gene SLC19A2 for the first time
      in the literature, we highlight the recognition of this syndrome--when
      megaloblastic anemia and diabetes mellitus coexists--and the role of thiamine
      replacement for the treatment of both disorders.

PMID- 18614592
TI  - Cytokine profiles in peripheral, placental and cord blood in an area of unstable
      malaria transmission in eastern Sudan.
AB  - BACKGROUND: Understanding the cytokine interactions that underlie both control
      and disease should be helpful when investigating the pathogenesis of malaria
      during pregnancy. Few data exists concerning pathogenesis of malaria during
      pregnancy in areas of unstable malaria transmission. OBJECTIVES: The study was
      conducted in New Halfa hospital, eastern Sudan, which is characterized by
      unstable malaria transmission to investigate the cytokine profiles in peripheral,
      placental and cord blood in parturient women. METHODS: Enzyme-linked
      immunosorbent assay was used to measure the concentrations of three cytokines,
      interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-10, in sera from
      peripheral, placental and cord blood of 87 Sudanese women. RESULTS: The
      concentrations of these cytokines were significantly higher in peripheral,
      placental sera from uninfected women than in sera from infected women. IFN-gamma
      concentrations were significantly lower in the cord sera from uninfected women in
      comparison to the infected ones. The levels of these cytokines were not
      significantly different between the primiparae and multipare. Cord sera in all
      groups showed lower levels of these cytokines. Strong positive correlations were
      observed between peripheral and placental cytokines. CONCLUSION: The immune
      responses that occur in placental, peripheral and cord blood were influenced by
      the malaria infections, irrespective of the parity. The immune response during
      Plasmodium falciparum infection is not different in the peripheral and placental
      compartments, further studies are required.

PMID- 18614594
TI  - Epidemiological and molecular analysis of astrovirus gastroenteritis in Dhaka
      City, Bangladesh.

PMID- 18614596
TI  - Perioperative beta-blockade, 2008: what does POISE tell us, and was our earlier
      caution justified?

PMID- 18614597
TI  - Continuous peripheral nerve blocks and anticoagulation.

PMID- 18614598
TI  - Performance of a minimally invasive cardiac output monitoring system
      (Flotrac/Vigileo).

PMID- 18614599
TI  - Patients scheduled for admission to intensive care unit: satisfaction with the
      information and frame of mind.

PMID- 18614600
TI  - Drug-eluting stent thrombosis in patients undergoing non-cardiac surgery.

PMID- 18614601
TI  - Significance of tricuspid valve dysfunction as a consequence of one-lung
      ventilation.

PMID- 18614602
TI  - A LMA CTrach for large patients.

PMID- 18614603
TI  - A patient with severe central core disease.

PMID- 18614604
TI  - Thrombolysis for massive pulmonary tumour embolism in a patient with cavoatrial
      renal carcinoma.

PMID- 18614605
TI  - A functional selection of viral genetic elements in cultured cells to identify
      hepatitis C virus RNA translation inhibitors.
AB  - We developed a functional selection system based on randomized genetic elements
      (GE) to identify potential regulators of hepatitis C virus (HCV) RNA translation,
      a process initiated by an internal ribosomal entry site (IRES). A retroviral HCV
      GE library was introduced into HepG2 cells, stably expressing the Herpes simplex
      virus thymidine kinase (HSV-TK) under the control of the HCV IRES. Cells that
      expressed transduced GEs inhibiting HSV-TK were selected via their resistance to
      ganciclovir. Six major GEs were rescued by PCR on the selected cell DNA and
      identified as HCV elements. We validated our strategy by further studying the
      activity of one of them, GE4, encoding the 5' end of the viral NS5A gene. GE4
      inhibited HCV IRES-, but not cap-dependent, reporter translation in human hepatic
      cell lines and inhibited HCV infection at a post-entry step, decreasing by 85%
      the number of viral RNA copies. This method can be applied to the identification
      of gene expression regulators.

PMID- 18614606
TI  - Dissection of reverse gyrase activities: insight into the evolution of a
      thermostable molecular machine.
AB  - Reverse gyrase is a peculiar DNA topoisomerase, specific of thermophilic
      microorganisms, which induces positive supercoiling into DNA molecules in an ATP
      dependent reaction. It is a modular enzyme and comprises an N-terminal helicase
      like module fused to a C-terminal topoisomerase IA-like domain. The exact
      molecular mechanism of this unique reaction is not understood, and a fundamental
      mechanistic question is how its distinct steps are coordinated. We studied the
      cross-talk between the components of this molecular motor and probed
      communication between the DNA-binding sites and the different activities (DNA
      relaxation, ATP hydrolysis and positive supercoiling). We show that the isolated
      ATPase and topoisomerase domains of reverse gyrase form specific physical
      interactions, retain their own DNA binding and enzymatic activities, and when
      combined cooperate to achieve the unique ATP-dependent positive supercoiling
      activity. Our results indicate a mutual effect of both domains on all individual
      steps of the reaction. The C-terminal domain shows ATP-independent topoisomerase
      activity, which is repressed by the N-terminal domain in the full-length enzyme;
      experiments with the isolated domains showed that the C-terminal domain has
      stimulatory influence on the ATPase activity of the N-terminal domain. In
      addition, the two domains showed a striking reciprocal thermostabilization
      effect.

PMID- 18614607
TI  - Intramolecularly folded G-quadruplex and i-motif structures in the proximal
      promoter of the vascular endothelial growth factor gene.
AB  - A polyguanine/polycytosine (polyG/polyC) tract in the proximal promoter of the
      vascular endothelial growth factor (VEGF) gene is essential for transcriptional
      activation. The guanine-rich (G-rich) and cytosine-rich (C-rich) strands on this
      tract are shown to form specific secondary structures, characterized as G
      quadruplexes and i-motifs, respectively. Mutational analysis of the G-rich strand
      combined with dimethyl sulfate (DMS) footprinting, a polymerase stop assay, and
      circular dichroism (CD) spectroscopy revealed that the G-quadruplex containing a
      1:4:1 double-chain reversal loop is the most thermodynamically stable
      conformation that this strand readily adopts. These studies provide strong
      evidence that the size of loop regions plays a critical role in determining the
      most favored folding pattern of a G-quadruplex. The secondary structure formed on
      the complementary C-rich strand was also determined by mutational analysis
      combined with Br(2) footprinting and CD spectroscopy. Our results reveal that at
      a pH of 5.9 this strand is able to form an intramolecular i-motif structure that
      involves six C-C(+) base pairs and a 2:3:2 loop configuration. Taken together,
      our results demonstrate that the G-quadruplex and i-motif structures are able to
      form on the G- and C-rich strands, respectively, of the polyG/polyC tract in the
      VEGF proximal promoter under conditions that favor the transition from B-DNA to
      non-B-DNA conformations.

PMID- 18614608
TI  - Cardiac rehabilitation: health characteristics and socio-economic status among
      those who do not attend.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is well documented, in randomised trials,
      to reduce mortality risk after myocardial infarction (MI). Selection of healthy
      patients for CR is a relatively unexplored problem. Our aims were to identify
      predictors of CR-attendance and to describe the prognosis as concerns mortality,
      re-admission and invasive treatment among CR-attendees as compared to CR-non
      attendees. METHODS: From a cohort of 138 290 persons aged 30-69 years, we
      identified consecutive MI patients, between 1 April 2000 and 31 March 2002. There
      were 206 MI patients, who survived until admission, and among the 200 who
      survived 30 days, 145 (72.5%) attended a comprehensive CR programme. Data were
      obtained from patient charts and from Danish population registers, and as a
      result we had no non-participation for the study. RESULTS: The 2-year mortality
      proportions for patients surviving the first 30 days of admission were 2.8 and
      21.8% among CR-attendees and CR-non-attendees, respectively (P < 0.0001). Among
      CR-non-attendees, there was a smaller fraction having an invasive treatment
      performed as compared with CR-attendees. By multiple logistic regression
      controlling for age and sex, CR-attendance was associated with chest pain,
      whereas CR-non-attendance was associated with low gross income, single living and
      inverted T-wave in the electrocardiogram. CONCLUSION: CR attendance rate was
      72.5%. Non-attendees have a higher mortality risk, which in part may be
      attributed to selection of healthy patients. Non-attendees are older and more
      likely to have atypical symptoms at admission, a low socioeconomic status and to
      live alone. Special attention is needed to improve CR attendance among such
      patients.

PMID- 18614609
TI  - Keep them in school: the importance of education as a protective factor against
      HIV infection among young South African women.
AB  - OBJECTIVE: To identify risk factors for HIV infection among young women aged 15
      24 years reporting one lifetime partner in South Africa. Design In 2003, we
      conducted a nationally representative household survey of sexual behaviour and
      HIV testing among 11 904 young people aged 15-24 years in South Africa. This
      analysis focuses on the subset of sexually experienced young women with only one
      reported lifetime sex partner (n = 1708). METHODS: Using the proximate
      determinants framework and the published literature we identified factors
      associated with HIV in young women. The associations between these factors and
      HIV infection were explored in multivariable logistic regression models. RESULTS:
      Of the young women, 15% reporting one lifetime partner were HIV positive. In
      multivariable analyses, young women who had not completed high school were more
      likely to be infected with HIV compared with those that had completed high school
      (AOR 3.75; 95% CI 1.34-10.46). CONCLUSIONS: Young South African women in this
      population were at high risk of HIV infection despite reporting only having one
      lifetime partner. Few individual level factors were associated with HIV
      infection, emphasizing the importance of developing HIV prevention interventions
      that address structural and partner level risk factors.

PMID- 18614611
TI  - Comments: The non-cancer mortality experience of male workers at British Nuclear
      Fuels plc, 1946-2005.

PMID- 18614612
TI  - Variation in bone morphogenetic protein 15 is not associated with spontaneous
      human dizygotic twinning.
AB  - BACKGROUND: Spontaneous dizygotic (DZ) twinning in humans is under genetic
      control. In sheep, heterozygous loss of function mutations in bone morphogenetic
      protein 15 (BMP15) increase ovulation and hence twinning rates. METHODS: To
      investigate the role of BMP15 in human twinning, we typed 14 common variants, 4
      rare novel variants initially detected by sequencing 279 mothers of DZ twins
      (MODZT) and 17 variants previously associated with premature ovarian failure
      (POF) in 933 DZ twinning families. We also typed five additional POF associated
      GDF9 variants. RESULTS: There was some evidence for association between DZ
      twinning and a common intronic BMP15 variant (rs3897937), but this was not
      significant after correction for multiple testing. Three of the four novel
      variants (p.Pro174Ser, p.Ala311Thr and p.Arg392Thr) occurred in 1-5 MODZT but
      were not detected in 1512 controls. We also detected three POF associated
      mutations in both BMP15 and GDF9 at low frequencies in MODZT and controls.
      CONCLUSIONS: We conclude that neither rare nor common BMP15 variants play a
      significant role in the variation in human DZ twinning.

PMID- 18614613
TI  - High levels of anandamide, an endogenous cannabinoid, block the growth of sheep
      preimplantation embryos by inducing apoptosis and reversible arrest of cell
      proliferation.
AB  - BACKGROUND: The process of implantation is mediated by various molecules, one of
      which is anandamide (AEA), a lipid signalling ligand belonging to the family of
      endocannabinoids. AEA exerts its effects on implantation by binding to the Type 1
      Cannabinoid Receptor (CB1-R), expressed in both blastocysts and uterus. We wanted
      to know whether the endocannabinoid signalling system was present also in the
      sheep reproductive tract and which kind of effect(s) AEA had on the development
      of sheep blastocysts in vitro. METHODS: We analysed the expression and activity
      of the endocannabinoid system in sheep reproductive tracts and blastocysts.
      Hatched sheep blastocysts were then exposed to AEA and its effect(s) were
      determined by TUNEL assay and by measuring the rate of necrosis and 5-bromo
      deoxyuridine incorporation. RESULTS: We show that the AEA signalling system is
      present in sheep and that high concentrations of AEA induce apoptosis and inhibit
      cell proliferation via a CB1-R-dependent mechanism. Indeed, AEA effects were
      blocked when sheep blastocysts were cultured in the presence of the CB1-R
      antagonist SR161417A. Moreover, AEA inhibition of cell proliferation was
      reversible, as arrested embryos resumed a normal growth rate upon AEA removal
      from the medium. CONCLUSIONS: Our results suggest that disturbed regulation of
      AEA signalling via CB1-R may be associated with pregnancy failure. AEA could
      lower the quality of blastocysts by inducing apoptosis and inhibiting cell
      proliferation, thus making them incompetent for implantation.

PMID- 18614614
TI  - Novel needle immersed vitrification: a practical and convenient method with
      potential advantages in mouse and human ovarian tissue cryopreservation.
AB  - BACKGROUND: Ovarian tissue cryopreservation may be a potential method of
      preserving fertility in women who have experienced gonadotoxic treatments. To
      improve the efficiency of existing cryopreservation, we developed a practical and
      convenient vitrification method named needle immersed vitrification (NIV), which
      required a less concentrated and minimum volume of vitrification solution.
      METHODS: Mouse ovaries and human ovarian cortex fragments were vitrified using
      the NIV method, the slow-freezing method or the dropping vitrification method.
      Their morphology, ultrastructure and viability were analyzed and compared with
      fresh group. RESULTS: Primordial follicles in human and mouse ovarian tissues
      vitrified by NIV were well preserved. In mice, the percentages of normal
      morphological primary and secondary follicles were greater in the NIV group than
      that in the slow-freezing group or dropping vitrification group (P < 0.001).
      Ultrastructure of the stromal cells was preserved better in the NIV group than
      the slow-freezing or the dropping vitrification group in both human (P = 0.039, P
      = 0.023, respectively) and mouse (both P < 0.001) models. The viability
      assessment on frozen-thawed human ovarian tissue strips revealed that the
      follicles and the stroma had a satisfactory viability in the NIV group. In mouse
      model, the ovarian functional restoration in the NIV group was the best among
      three freezing groups, which was demonstrated by follicle counting in grafts
      after transplantation (P = 0.009 and P = 0.010 versus slow freezing and dropping
      vitrification, respectively). The cleavage rate of oocytes from grafts of the NIV
      group was most similar to that observed in the fresh group. CONCLUSIONS: The NIV
      method could facilitate vitrification process, maximize the cooling rate and
      reduce the toxicity of the vitrification solution with a minimal volume of less
      concentrated cryoprotectants. NIV was practical and convenient for
      cryopreservation of ovarian tissues.

PMID- 18614615
TI  - Do doctors discuss fertility issues before they treat young patients with cancer?
AB  - BACKGROUND: Many children treated for cancer are at risk of infertility, but for
      girls and prepubertal boys, all fertility preservation techniques remain
      experimental. We have assessed UK practice relating to information provision
      about the effects of cancer treatment on fertility and options for fertility
      preservation. METHODS: Paediatric oncologists prospectively completed a data form
      for each new patient registered over a 12 month period. RESULTS: Data were
      available on 1030 patients (68% of total registered). The effect of cancer
      treatment on fertility was discussed with 63% of patients. Of these, 61% were
      judged to be at high or medium risk of fertility problems. Discussions took place
      more commonly with boys than girls; the commonest reason for discussion not
      occurring was young age. The majority (83%) of post-pubertal boys assessed as
      high/medium risk of infertility were referred for semen cryopreservation. This
      rate fell to 39% of those in early puberty. Only 1% (n=4) of girls were referred
      to an assisted conception unit. CONCLUSIONS: These data indicate a high awareness
      of the potential adverse effects of therapy on fertility among UK paediatric
      oncologists. High referral rates for older boys indicate that current guidelines
      are followed, but there is a need for fertility preservation techniques for girls
      and younger boys.

PMID- 18614616
TI  - What next for preimplantation genetic screening? Randomized clinical trial in
      assessing PGS: necessary but not sufficient.
AB  - The randomized clinical trial (RCT) is a powerful experimental design that when
      properly executed produces generalizable results. Conducting a RCT becomes
      complex when technical skills are required. Without requisite skills, a RCT may
      yield misleading results, an elegant RCT unwittingly generating spurious results
      due to technical inexperience. This pitfall is applicable to procedures used to
      evaluate assisted reproductive technologies. RCTs assessing the value of
      preimplantation genetic screening, also called preimplantation genetic diagnosis
      for aneuploidy testing--require three general prerequisites--proper study design,
      skilled operators (embryo biopsy), and skilled laboratory cytogeneticists
      (diagnosis). Lacking either of the latter two, even an elegantly designed RCT is
      not necessarily valid.

PMID- 18614617
TI  - Oxidative stress-induced renal angiotensin AT1 receptor upregulation causes
      increased stimulation of sodium transporters and hypertension.
AB  - Reactive oxygen species have emerged as important molecules in cardiovascular
      dysfunction such as diabetes and hypertension. Recent work has shown that
      oxidative stress and angiotensin II signaling mutually regulate each other by
      multiple mechanisms and contribute to the development of hypertension. Most of
      the known biological actions of angiotensin II can be attributed to AT1
      receptors. The present study was carried out to investigate the role of renal AT1
      receptor signaling in oxidative stress-mediated hypertension. Male Sprague-Dawley
      rats received tap water (control) or 30 mM L-buthionine sulfoximine (BSO), an
      oxidant, with and without 1 mM tempol (an antioxidant) for 2 wk. Compared with
      control rats, BSO-treated rats exhibited increased oxidative stress and reduced
      antioxidant levels and developed hypertension. BSO treatment also caused
      increased renal proximal tubular AT1 receptor protein abundance, message levels,
      and ligand binding. In these rats, angiotensin II caused significantly higher
      accumulation of inositol trisphosphate (IP3) and phospholipase C (PLC) activation
      which was sensitive to blockade by AT1 but not to AT2 antagonist. Also,
      angiotensin II-mediated, AT1-dependent MAP kinase, Na-K-ATPase, and Na/H
      exchanger 3 activation was higher in BSO-treated rats than in control rats.
      Tempol supplementation of BSO-treated rats restored redox status, normalized AT1
      receptor expression, and decreased blood pressure. Tempol also normalized the
      angiotensin II-mediated, AT1-dependent IP3 accumulation and PLC, MAP kinase, Na-K
      ATPase, and Na/H exchanger 3 stimulation. These data suggest that oxidative
      stress leads to AT1 receptor upregulation, which in turn causes overstimulation
      of sodium transporters and subsequently contributes to sodium retention and
      hypertension. Tempol, while reducing oxidative stress, normalizes AT1 receptor
      signaling and decreases blood pressure.

PMID- 18614618
TI  - Characterization of the Hoechst 33342 side population from normal and malignant
      human renal epithelial cells.
AB  - The fundamental changes which predispose for renal cell carcinoma (RCC) are
      poorly characterized. It is hypothesized that "cancer stem cells" may be
      influential in carcinogenesis, and the epithelial side population (SP) is
      enriched for stemlike cells in other epithelial cancers. In this study, we have
      isolated and characterized the SP and non-SP (NSP) populations from normal (NK)
      and malignant (RCC) human kidney tissue. NK specimens were taken from patients
      undergoing non-renal cancer surgery and paired malignant and macroscopically
      normal tissue samples were taken from patients undergoing surgery for RCC. The
      Hoechst 33342 dye efflux technique was used to isolate epithelial SP and NSP from
      normal and malignant human renal tissue. Cellular subpopulations were phenotyped
      for lineage, cell cycle, and putative stem cell markers, and functionally
      characterized using in vitro colony-forming and proliferation assays. The SP
      constituted 3.8 +/- 0.4 and 5.9 +/- 0.9% of epithelial cells in NK and RCC,
      respectively, of which 14.1 +/- 3.5 and 13.2 +/- 3.6% were shown to be in G(0).
      SP cells demonstrated greater proliferative potential in colony-forming
      efficiency, long-term culture, and spheroids assays and were shown to be
      maintained upon tissue culture passage. We have shown that the renal SP is
      enriched for quiescent cells, with a high proliferative capacity and stemlike
      properties. The population is, however, heterogeneous, confirming that the terms
      "SP cell" and "stem cell" cannot be used interchangeably.

PMID- 18614619
TI  - Reduction of chronic allograft nephropathy by inhibition of extracellular signal
      regulated kinase 1 and 2 signaling.
AB  - Chronic allograft nephropathy (CAN), the most common cause of late kidney
      allograft failure, is not effectively prevented by immunosuppressive regimens.
      Activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) via MEK
      mediates actions of various growth factors, including transforming growth factor
      (TGF)-beta1, which plays a key role in CAN. Hence, we tested the therapeutic
      potential of MEK-ERK1/2 signaling disruption to prevent CAN. Kidneys from
      C57BL/6J (H-2(b)) mice were transplanted to bilaterally nephrectomized BALB/c (H
      2(d)) mice. At 14 days after transplantation, the recipients were subjected to 28
      days of treatment with the MEK inhibitor CI-1040. All six CI-1040-treated
      allografts survived, while two of seven grafts in the vehicle-treated group were
      lost. At the end of the experiment, the function and structure of grafts in the
      CI-1040-treated group were significantly preserved, as indicated by lower levels
      of serum creatinine or blood urea nitrogen than in the vehicle-treated group [30
      +/- 6 vs. 94 +/- 39 microM creatinine (P = 0.0015) and 22 +/- 8 vs. 56 +/- 25 mM
      BUN (P = 0.0054)] and reduced CAN in the CI-1040-treated group compared with
      vehicle controls (CAN score = 4.2 vs. 10.3, P = 0.0119). The beneficial effects
      induced by CI-1040 were associated with reduction of ERK1/2 phosphorylation and
      TGFbeta1 levels in grafts. Also, CI-1040 potently suppressed not only TGFbeta
      biosynthesis in kidney cell cultures but also antiallograft immune responses in
      vitro and in vivo. Our data suggest that interference of MEK-ERK1/2 signaling
      with a pharmacological agent (e.g., CI-1040) has therapeutic potential to prevent
      CAN in kidney transplantation.

PMID- 18614620
TI  - Nicotinic acetylcholine receptor expression and regulation in the rat kidney
      after ischemia-reperfusion injury.
AB  - The cholinergic anti-inflammatory pathway is a mechanism whereby local
      inflammation is modulated by the brain via the vagus nerve and nicotinic
      acetylcholine receptors (nAChRs). The nAChR family are ligand-gated ion channels
      that consist of many different subtypes formed by the specific assembly of five
      polypeptide subunits including alpha1-10, beta1-4, gamma, delta, and epsilon. The
      alpha7 receptor (alpha7nAChR) mediates the anti-inflammatory effects of
      cholinergic stimulation. We recently demonstrated that cholinergic agonists
      attenuate renal ischemia-reperfusion (I/R) injury in rats. We also showed that
      tubular epithelial cells express functional nAChRs in vitro. The current studies
      report the expression, localization, and regulation of the alpha7nAChR in the rat
      kidney after I/R injury. We also examined, in this model, potential interactions
      between cholinergic stimulation and the STAT3 pathway, a key signaling cascade
      that has been linked to alpha7nAChR activation. RT-PCR and immunohistochemistry
      showed constitutive expression of many nAChR subunits. Immunohistochemistry
      localized basal alpha7nAChR expression to the endothelium of cortical peritubular
      capillaries, and its distribution was upregulated after I/R injury. Western
      blotting also showed an increase in alpha7nAChR subunit protein after renal I/R
      injury. Interestingly, pretreatment with nicotine, which improves the outcome
      after renal I/R injury, reduced the alpha7nAChR protein after I/R injury.
      Finally, we found that I/R injury stimulated the STAT3 pathway, whereas
      pretreatment with nicotine downregulated its activation. These results suggest
      that the alpha7nAChR plays an important role in the pathophysiology of renal I/R
      injury.

PMID- 18614621
TI  - Expression profiling of hepatic genes associated with lipid metabolism in
      nephrotic rats.
AB  - Hyperlipidemia is one of the major features of nephrotic syndrome (NS). Although
      many factors have been implicated in the pathogenesis of NS-related dyslipidemia,
      the underlying mechanisms remain largely uncharacterized. The present study was
      designed to examine the gene profile associated with lipid metabolism in the
      livers of nephrotic rats. NS was created in male Sprague-Dawley rats (n = 6)
      receiving sequential intraperitoneal injections of puromycin aminonucleoside.
      Analysis by Affymetrix assay, quantitative RT-PCR, and Northern and Western
      blotting revealed 21 genes associated with cholesterol and fatty acid metabolism.
      Eight genes involved in cholesterol metabolism, Apo A-I, Acly, Acat, Mpd, Fdps,
      Ss, Lss, and Nsdhl, were significantly upregulated under NS. Four genes involved
      in fatty acid biosynthesis, Acc, FAS, ELOVL 2, and ELOVL6, and three critical for
      triglyceride biosynthesis, Gpam, Agpat 3, and Dgat 1, were significantly
      upregulated, whereas two genes involved in fatty acid oxidation, Dci and MCAD,
      were downregulated. Expression of several genes in sterol-regulatory element
      binding protein (SREBP)-1 activation was also aberrantly altered in nephrotic
      livers. The expression and transcriptional activity of SREBP-1 but not SREBP-2
      were increased in nephrotic rats as assessed by real-time PCR, immunoblotting,
      and gel shift assays. The upregulation of hepatic genes involved in cholesterol
      biosynthesis may play an important role in the pathogenesis of
      hypercholesterolemia, whereas upregulation of genes participating in hepatic
      fatty acid and triglyceride biosynthesis and downregulation of genes involved in
      hepatic fatty acid oxidation may contribute to hypertriglyceridemia in nephrotic
      rats. Activation of SREBP-1 transcription factor may represent an underlying
      molecular mechanism of hyperlipidemia in NS.

PMID- 18614622
TI  - G418-mediated ribosomal read-through of a nonsense mutation causing autosomal
      recessive proximal renal tubular acidosis.
AB  - Autosomal recessive proximal renal tubular acidosis is caused by mutations in the
      SLC4A4 gene encoding the electrogenic sodium bicarbonate cotransporter NBCe1-A.
      The mutations that have been characterized thus far result in premature
      truncation, mistargeting, or decreased function of the cotransporter. Despite
      bicarbonate treatment to correct the metabolic acidosis, extrarenal
      manifestations persist, including glaucoma, cataracts, corneal opacification, and
      mental retardation. Currently, there are no known therapeutic approaches that can
      specifically target mutant NBCe1-A proteins. In the present study, we tested the
      hypothesis that the NBCe1-A-Q29X mutation can be rescued in vitro by treatment
      with aminoglycoside antibiotics, which are known for their ability to suppress
      premature stop codons. As a model system, we cloned the NBCe1-A-Q29X mutant into
      a vector lacking an aminoglycoside resistance gene and transfected the mutant
      cotransporter in HEK293-H cells. Cells transfected with the NBCe1-A-Q29X mutant
      failed to express the cotransporter because of the premature stop codon.
      Treatment of the cells with G418 significantly increased the expression of the
      full-length cotransporter, as assessed by immunoblot analysis. Furthermore,
      immunocytochemical studies demonstrated that G418 treatment induced cotransporter
      expression on the plasma membrane whereas in the absence of G418, NBCe1-A-Q29X
      was not expressed. In HEK293-H cells transfected with the NBCe1-A-Q29X mutant not
      treated with G418, NBCe1-A-mediated flux was not detectable. In contrast, in
      cells transfected with the NBCe1-A-Q29X mutant, G418 treatment induced Na(+)- and
      HCO(3)(-)-dependent transport that did not differ from wild-type NBCe1-A
      function. G418 treatment in mock-transfected cells was without effect. In
      conclusion, G418 induces ribosomal read-through of the NBCe1-A-Q29X mutation in
      HEK293-H cells. These findings represent the first evidence that in the presence
      of the NBCe1-A-Q29X mutation that causes proximal renal tubular acidosis, full
      length functional NBCe1-A protein can be produced. Our results provide the first
      demonstration of a mutation in NBCe1-A that has been treated in a targeted and
      specific manner.

PMID- 18614623
TI  - Channels for water efflux and influx involved in volume regulation of murine
      spermatozoa.
AB  - The nature of the membrane channels mediating water transport in murine
      spermatozoa adjusting to anisotonic conditions was investigated. The volume of
      spermatozoa subjected to physiologically relevant hypotonic conditions either
      simultaneously, or after isotonic pre-incubation, with putative water transport
      inhibitors was monitored. Experiments in which quinine prevented osmolyte efflux,
      and thus regulatory volume decrease (RVD), revealed whether water influx or
      efflux was being inhibited. There was no evidence that sodium-dependent solute
      transporters or facilitative glucose transporters were involved in water
      transport during RVD of murine spermatozoa since phloretin, cytochalasin B and
      phloridzin had no effect on volume regulation. However, there was evidence that
      Hg(2+)- and Ag(+)-sensitive channels were involved in water transport and the
      possibility that they include aquaporin 8 is discussed. Toxic effects of these
      heavy metals were ruled out by evidence that mitochondrial poisons had no such
      effect on volume regulation.

PMID- 18614624
TI  - Effects of Kaempferia parviflora extracts on reproductive parameters and
      spermatic blood flow in male rats.
AB  - Krachaidum (KD, Kaempferia parviflora Wall. Ex. Baker), a native plant of
      Southeast Asia, is traditionally used to enhance male sexual function. However,
      only few scientific data in support of this anecdote have been reported. The
      present study investigated the effects of feeding three different extracts of KD
      (alcohol, hexane, and water extracts) for 3-5 weeks on the reproductive organs,
      the aphrodisiac activity, fertility, sperm motility, and blood flow to the testis
      of male rats. Sexual performances (mount latency, mount frequency, ejaculatory
      latency, post-ejaculatory latency) and sperm motility were assessed by a video
      camera and computer-assisted sperm analysis respectively, while blood flow to the
      testis was measured by a directional pulsed Doppler flowmeter. The results showed
      that all extracts of KD had virtually no effect on the reproductive organ weights
      even after 5 weeks. However, administration of the alcohol extract at a dose of
      70 mg/kg body weight (BW)/day for 4 weeks significantly decreased mount and
      ejaculatory latencies when compared with the control. By contrast, hexane and
      water extracts had no influence on any sexual behavior parameters. All types of
      extracts of KD had no effect on fertility or sperm motility. On the other hand,
      alcohol extract produced a significant increase in blood flow to the testis
      without affecting the heart rate and mean arterial blood pressure. In a separate
      study, an acute effect of alcohol extract of KD on blood flow to the testis was
      investigated. Intravenous injection of KD at doses of 10, 20, and 40 mg/kg BW
      caused dose-dependent increases in blood flow to the testis. The results indicate
      that alcohol extract of KD had an aphrodisiac activity probably via a marked
      increase in blood flow to the testis.

PMID- 18614625
TI  - Novel immunocontraceptive targets in mammals: uterine secretions and the
      conceptus; a marsupial approach.
AB  - We report the first immunocontraceptive trial in mammals using a uterine-secreted
      protein, the marsupial shell coat protein 4 (CP4). The marsupial shell coat,
      which surrounds the conceptus for 60-80% of gestation, is secreted by the uterine
      epithelium. Following immunization against glutathione S-transferase (GST)-CP4,
      the fertility of female common brushtail possums (n=6) was significantly reduced
      (P=0.000), and this reduction in fertility was positively correlated with the
      maximum GST-CP4 humoral immune response (P=0.025). Ultrastructural examination of
      the reproductive tract indicated that the cell-mediated immune response against
      GST-CP4 targeted the shell coat, the shell-free conceptus and the uterine
      glandular epithelium, thus preventing normal conceptus development and uterine
      secretion of shell coat proteins and nutrients. These results show that uterine
      secreted proteins are promising immunocontraceptive targets, especially in pest
      mammal species, e.g. possum, rabbit and horse, that have uterine-secreted
      additions to embryonic coats, or that have late implantation requiring uterine
      nutrient provisioning from secretions.

PMID- 18614626
TI  - A reappraisal of the factors involved in in vitro initiation of the acrosome
      reaction in chicken spermatozoa.
AB  - Chicken spermatozoa may remain in the female oviduct for a prolonged period
      before induction of the acrosome reaction on contact with the inner perivitelline
      layer (IPVL). By contrast, the acrosome reaction may be induced very rapidly in
      vitro in the presence of IPVL and Ca(2+). In the present study, we examined the
      extent to which the chicken acrosome reaction can be induced in media of various
      compositions in the presence or absence of IPVL and/or Ca(2+) and other factors
      known to be efficient in mammals. We also compared the efficacy of perivitelline
      layer (PL) taken at various states of oocyte maturation in initiating the
      reaction. The acrosome reaction was induced in less than 5 min in the presence of
      Ca(2+) and IPVL. Incubation of spermatozoa in different saline media (Beltsville
      poultry semen extender (BPSE); Dulbecco's modified eagle medium; NaCl-TES buffer)
      without IPVL showed a significant induction of acrosome reaction in BPSE
      supplemented with 5 mM Ca(2+) and in the three media after supplementation with
      Ca(2+) and Ca(2+) ionophore A23187. By contrast, the acrosome reaction was never
      induced without Ca(2+). BSA, NaHCO(3), and progesterone did not stimulate the
      acrosome reaction. Ca(2+) plus PL taken at various physiological states (follicle
      IPVL, ovulated IPVL, oviposited IPVL, and/or outer perivitelline layer) strongly
      stimulated the acrosome reaction, the latest states being the most efficient.
      Although PL induced the acrosome reaction in the presence of extracellular
      Ca(2+), it was not possible to induce hyperactivation in chicken spermatozoa.
      Taken together, these results emphasize the central role of Ca(2+) in the in
      vitro initiation of the acrosome reaction in chickens and show specific features
      of this induction in birds.

PMID- 18614627
TI  - Comparing the risk of work-related injuries between immigrants to Canada and
      Canadian-born labour market participants.
AB  - OBJECTIVES: To examine the burden of work-related injuries among immigrants to
      Canada compared to Canadian-born labour force participants. METHODS: Using data
      from the 2003 and 2005 Canadian Community Health Surveys (n = 99,115), two
      nationally representative population samples, we examined the risk of self
      reported, activity limiting work-related injuries among immigrants with varying
      time periods since arrival in Canada. Models were adjusted for hours of work in
      the last 12 months as well as various demographic and work-related variables.
      RESULTS: Immigrant men in their first 5 years in Canada reported lower rates of
      activity limiting injuries compared to Canadian-born respondents. Surprisingly,
      the percentage of injuries that required medical attention was much higher among
      recent immigrants compared to Canadian-born respondents, resulting in an
      increased risk of activity limiting injuries requiring medical attention among
      immigrant men compared to Canadian-born labour force participants. No excess risk
      was found among female immigrants compared to Canadian-born female labour market
      participants. CONCLUSIONS: Immigrant men in their first 5 years in Canada are at
      increased risk of work-related injuries that require medical attention. A similar
      risk is not present among immigrant women. Further, given differences in the
      number of activity limiting injuries requiring medical attention across immigrant
      groups, we believe this excess risk among immigrant men may be underestimated in
      the current data source. Future research should attempt to fully capture the
      barriers faced by immigrants in obtaining safe employment, the number of injuries
      that are sustained by immigrants while working, and the consequences of these
      injuries.

PMID- 18614628
TI  - The NY-1 hantavirus Gn cytoplasmic tail coprecipitates TRAF3 and inhibits
      cellular interferon responses by disrupting TBK1-TRAF3 complex formation.
AB  - Pathogenic hantaviruses replicate within human endothelial cells and cause two
      diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary
      syndrome. In order to replicate in endothelial cells pathogenic hantaviruses
      inhibit the early induction of beta interferon (IFN-beta). Expression of the
      cytoplasmic tail of the pathogenic NY-1 hantavirus Gn protein is sufficient to
      inhibit RIG-I- and TBK1-directed IFN responses. The formation of TBK1-TRAF3
      complexes directs IRF-3 phosphorylation, and both IRF-3 and NF-kappaB activation
      are required for transcription from the IFN-beta promoter. Here we report that
      the NY-1 virus (NY-1V) Gn tail inhibits both TBK1-directed NF-kappaB activation
      and TBK1-directed transcription from promoters containing IFN-stimulated response
      elements. The NY-1V Gn tail coprecipitated TRAF3 from cellular lysates, and
      analysis of TRAF3 deletion mutants demonstrated that the TRAF3 N terminus is
      sufficient for interacting with the NY-1V Gn tail. In contrast, the Gn tail of
      the nonpathogenic hantavirus Prospect Hill virus (PHV) failed to coprecipitate
      TRAF3 or inhibit NF-kappaB or IFN-beta transcriptional responses. Further,
      expression of the NY-1V Gn tail blocked TBK1 coprecipitation of TRAF3 and
      infection by NY-1V, but not PHV, blocked the formation of TBK1-TRAF3 complexes.
      These findings indicate that the NY-1V Gn cytoplasmic tail forms a complex with
      TRAF3 which disrupts the formation of TBK1-TRAF3 complexes and downstream
      signaling responses required for IFN-beta transcription.

PMID- 18614629
TI  - Human parainfluenza virus type 1 C proteins are nonessential proteins that
      inhibit the host interferon and apoptotic responses and are required for
      efficient replication in nonhuman primates.
AB  - Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create
      rHPIV1-P(C-), a virus in which expression of the C proteins (C', C, Y1, and Y2)
      was silenced without affecting the amino acid sequence of the P protein.
      Infectious rHPIV1-P(C-) was readily recovered from cDNA, indicating that the four
      C proteins were not essential for virus replication. Early during infection in
      vitro, rHPIV1-P(C-) replicated as efficiently as wild-type (wt) HPIV1, but its
      titer subsequently decreased coincident with the onset of an extensive cytopathic
      effect not observed with wt rHPIV1. rHPIV1-P(C-) infection, but not wt rHPIV1
      infection, induced caspase 3 activation and nuclear fragmentation in LLC-MK2
      cells, identifying the HPIV1 C proteins as inhibitors of apoptosis. In contrast
      to wt rHPIV1, rHPIV1-P(C-) and rHPIV1-C(F170S), a mutant encoding an F170S
      substitution in C, induced interferon (IFN) and did not inhibit IFN signaling in
      vitro. However, only rHPIV1-P(C-) induced apoptosis. Thus, the anti-IFN and
      antiapoptosis activities of HPIV1 were separable: both activities are disabled in
      rHPIV1-P(C-), whereas only the anti-IFN activity is disabled in rHPIV1-C(F170S).
      In African green monkeys (AGMs), rHPIV1-P(C-) was considerably more attenuated
      than rHPIV1-C(F170S), suggesting that disabling the anti-IFN and antiapoptotic
      activities of HPIV1 had additive effects on attenuation in vivo. Although rHPIV1
      P(C-) protected against challenge with wt HPIV1, its highly restricted
      replication in AGMs and in primary human airway epithelial cell cultures suggests
      that it might be overattenuated for use as a vaccine. Thus, the C proteins of
      HPIV1 are nonessential but have anti-IFN and antiapoptosis activities required
      for virulence in primates.

PMID- 18614630
TI  - Epstein-Barr virus BART microRNAs are produced from a large intron prior to
      splicing.
AB  - Latent Epstein-Barr virus (EBV) infection is associated with several
      lymphoproliferative disorders, including posttransplant lymphoma, Hodgkin's
      disease, and Burkitt's lymphoma, as well as nasopharyngeal carcinoma (NPC).
      Twenty-nine microRNAs (miRNAs) have been identified that are transcribed during
      latent infection from three clusters in the EBV genome. Two of the three clusters
      of miRNAs are made from the BamHI A rightward transcripts (BARTs), a set of
      alternatively spliced transcripts that are highly abundant in NPC but have not
      been shown to produce a detectable protein. This study indicates that while the
      BART miRNAs are located in the first four introns of the transcripts, processing
      of the pre-miRNAs from the primary transcript occurs prior to completion of the
      splicing reaction. Additionally, production of the BART miRNAs correlates with
      accumulation of a spliced mRNA in which exon 1 is joined directly to exon 3,
      suggesting that this form of the transcript may favor production of miRNAs.
      Sequence variations and processing of pre-miRNAs to the mature form also may
      account for various differences in miRNA abundance. Importantly, residual
      intronic pieces that result from processing of the pre-miRNAs were detected in
      the nucleus. The predicted structures of these pieces suggest there is a bias or
      temporal pattern to the production of the individual pre-miRNAs. These findings
      indicate that multiple factors contribute to the production of the BART miRNAs
      and to the apparent differences in abundance between the individual miRNAs of the
      cluster.

PMID- 18614632
TI  - An insect virus-encoded microRNA regulates viral replication.
AB  - MicroRNAs (miRNAs) are small ( approximately 22 nucleotides) noncoding RNAs which
      play an essential role in gene regulation and affect a wide range of processes,
      including development, differentiation, and oncogenesis. Here we report the
      identification of the first miRNA from an insect virus, derived from the major
      capsid protein (MCP) gene in Heliothis virescens ascovirus (HvAV) (HvAV-miR-1).
      Although MCP was abundantly expressed at all time points 24 h after infection,
      HvAV-miR-1 expression was strictly regulated and specifically detected from 96 h
      postinfection. HvAV-miR-1 expression coincided with a marked reduction of the
      expression of HvAV DNA polymerase I, which is a predicted target. Ectopic
      expression of full-length and truncated versions of MCP retaining the miRNA
      sequence significantly reduced DNA polymerase I transcript levels and inhibited
      viral replication. Our results indicate that HvAV-miR-1 directs transcriptional
      degradation of DNA polymerase I and regulates HvAV replication. These findings
      are congruent with recent reports that miR-BART-2 regulates Epstein-Barr virus
      DNA polymerase expression and suggest that virus-encoded miRNA regulation of
      virus replication may be a general phenomenon.

PMID- 18614631
TI  - Marked epitope- and allele-specific differences in rates of mutation in human
      immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes
      in acute/early HIV-1 infection.
AB  - During acute human immunodeficiency virus type 1 (HIV-1) infection, early host
      cellular immune responses drive viral evolution. The rates and extent of these
      mutations, however, remain incompletely characterized. In a cohort of 98
      individuals newly infected with HIV-1 subtype B, we longitudinally characterized
      the rates and extent of HLA-mediated escape and reversion in Gag, Pol, and Nef
      using a rational definition of HLA-attributable mutation based on the analysis of
      a large independent subtype B data set. We demonstrate rapid and dramatic HIV
      evolution in response to immune pressures that in general reflect established
      cytotoxic T-lymphocyte (CTL) response hierarchies in early infection. On a
      population level, HLA-driven evolution was observed in approximately 80% of
      published CTL epitopes. Five of the 10 most rapidly evolving epitopes were
      restricted by protective HLA alleles (HLA-B*13/B*51/B*57/B*5801; P = 0.01),
      supporting the importance of a strong early CTL response in HIV control.
      Consistent with known fitness costs of escape, B*57-associated mutations in Gag
      were among the most rapidly reverting positions upon transmission to non-B*57
      expressing individuals, whereas many other HLA-associated polymorphisms displayed
      slow or negligible reversion. Overall, an estimated minimum of 30% of observed
      substitutions in Gag/Pol and 60% in Nef were attributable to HLA-associated
      escape and reversion events. Results underscore the dominant role of immune
      pressures in driving early within-host HIV evolution. Dramatic differences in
      escape and reversion rates across codons, genes, and HLA restrictions are
      observed, highlighting the complexity of viral adaptation to the host immune
      response.

PMID- 18614633
TI  - A hepatitis C virus cis-acting replication element forms a long-range RNA-RNA
      interaction with upstream RNA sequences in NS5B.
AB  - The genome of hepatitis C virus (HCV) contains cis-acting replication elements
      (CREs) comprised of RNA stem-loop structures located in both the 5' and 3'
      noncoding regions (5' and 3' NCRs) and in the NS5B coding sequence. Through the
      application of several algorithmically independent bioinformatic methods to
      detect phylogenetically conserved, thermodynamically favored RNA secondary
      structures, we demonstrate a long-range interaction between sequences in the
      previously described CRE (5BSL3.2, now SL9266) with a previously predicted
      unpaired sequence located 3' to SL9033, approximately 200 nucleotides upstream.
      Extensive reverse genetic analysis both supports this prediction and demonstrates
      a functional requirement in genome replication. By mutagenesis of the Con-1
      replicon, we show that disruption of this alternative pairing inhibited
      replication, a phenotype that could be restored to wild-type levels through the
      introduction of compensating mutations in the upstream region. Substitution of
      the CRE with the analogous region of different genotypes of HCV produced
      replicons with phenotypes consistent with the hypothesis that both local and long
      range interactions are critical for a fundamental aspect of genome replication.
      This report further extends the known interactions of the SL9266 CRE, which has
      also been shown to form a "kissing loop" interaction with the 3' NCR (P. Friebe,
      J. Boudet, J. P. Simorre, and R. Bartenschlager, J. Virol. 79:380-392, 2005), and
      suggests that cooperative long-range binding with both 5' and 3' sequences
      stabilizes the CRE at the core of a complex pseudoknot. Alternatively, if the
      long-range interactions were mutually exclusive, the SL9266 CRE may function as a
      molecular switch controlling a critical aspect of HCV genome replication.

PMID- 18614634
TI  - A single amino acid residue change in the P protein of parainfluenza virus 5
      elevates viral gene expression.
AB  - Parainfluenza virus 5 (PIV5) is a prototypical paramyxovirus. The V/P gene of
      PIV5 encodes two mRNA species through a process of pseudotemplated insertion of
      two G residues at a specific site during transcription, resulting in two viral
      proteins, V and P, whose N termini of 164 amino acid residues are identical.
      Previously it was reported that mutating six amino acid residues within this
      identical region results in a recombinant PIV5 (rPIV5-CPI-) that exhibits
      elevated viral protein expression and induces production of cytokines, such as
      beta interferon and interleukin 6. Because the six mutations correspond to the
      shared region of the V protein and the P protein, it is not clear whether the
      phenotypes associated with rPIV5-CPI- are due to mutations in the P protein
      and/or mutations in the V protein. To address this question, we used a minigenome
      system and recombinant viruses to study the effects of mutations on the functions
      of the P and V proteins. We found that the P protein with six amino acid residue
      changes (Pcpi-) was more efficient than wild-type P in facilitating replication
      of viral RNA, while the V protein with six amino acid residue changes (Vcpi-)
      still inhibits minigenome replication as does the wild-type V protein. These
      results indicate that elevated viral gene expression in rPIV5-CPI- virus-infected
      cells can be attributed to a P protein with an increased ability to facilitate
      viral RNA synthesis. Furthermore, we found that a single amino acid residue
      change at position 157 of the P protein from Ser (the residue in the wild-type P
      protein) to Phe (the residue in Pcpi-) is sufficient for elevated viral gene
      expression. Using mass spectrometry and (33)P labeling, we found that residue
      S157 of the P protein is phosphorylated. Based on these results, we propose that
      phosphorylation of the P protein at residue 157 plays an important role in
      regulating viral RNA replication.

PMID- 18614637
TI  - Natural killer cells regulate T-cell proliferation during human parainfluenza
      virus type 3 infection.
AB  - Human parainfluenza virus type 3 (HPIV3) is a major respiratory pathogen in
      humans. Failure to induce immunological memory associated with HPIV3 infection
      has been attributed to inhibition of lymphocyte proliferation. We demonstrate
      that the inability of mixed lymphocytes to respond to virally infected antigen
      presenting cells is due to an interleukin-2-dependent, nonapoptotic mechanism
      involving natural killer (NK) cells and their influence is exerted in a contact
      dependent manner. These results suggest a novel regulatory mechanism for NK cells
      during HPIV3 infection, offering an explanation for viral persistence and poor
      memory responses.

PMID- 18614636
TI  - Common marmosets (Callithrix jacchus) as a nonhuman primate model to assess the
      virulence of eastern equine encephalitis virus strains.
AB  - Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral
      disease in North America (NA) and is a potential biological weapon. However,
      genetically and antigenically distinct strains from South America (SA) have
      seldom been associated with human disease or mortality despite serological
      evidence of infection. Because mice and other small rodents do not respond
      differently to the NA versus SA viruses like humans, we tested common marmosets
      (Callithrix jacchus) by using intranasal infection and monitoring for weight
      loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected
      animals either died or were euthanized on day 4 or 5 after infection due to
      anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy
      and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8
      to 3.1 log(10) PFU/ml on day 2 or 4 after infection, but there was no detectable
      viremia in the NA EEEV-infected animals. In contrast, virus was detected in the
      brain, liver, and muscle of the NA EEEV-infected animals at the time of
      euthanasia or death. Similar to the brain lesions described for human EEE, the NA
      EEEV-infected animals developed meningoencephalitis in the cerebral cortex with
      some perivascular hemorrhages. The findings of this study identify the common
      marmoset as a useful model of human EEE for testing antiviral drugs and vaccine
      candidates and highlight their potential for corroborating epidemiological
      evidence that some, if not all, SA EEEV strains are attenuated for humans.

PMID- 18614635
TI  - Distinct requirements of adenovirus E1b55K protein for degradation of cellular
      substrates.
AB  - The E1b55K and E4orf6 proteins of adenovirus type 5 (Ad5) assemble into a complex
      together with cellular proteins including cullin 5, elongins B and C, and Rbx1.
      This complex possesses E3 ubiquitin ligase activity and targets cellular proteins
      for proteasome-mediated degradation. The ligase activity has been suggested to be
      responsible for all functions of E1b55K/E4orf6, including promoting efficient
      viral DNA replication, preventing a cellular DNA damage response, and stimulating
      late viral mRNA nuclear export and late protein synthesis. The known cellular
      substrates for degradation by E1b55K/E4orf6 are the Mre11/Rad50/Nbs1 DNA repair
      complex, the tumor suppressor p53, and DNA ligase IV. Here we show that the
      degradation of individual targets can occur independently of other substrates.
      Furthermore, we identify separation-of-function mutant forms of E1b55K that can
      distinguish substrates for binding and degradation. Our results identify distinct
      regions of E1b55K that are involved in substrate recognition but also imply that
      there are additional requirements beyond protein association. These mutant
      proteins will facilitate the determination of the relevance of specific
      substrates to the functions of E1b55K in promoting infection and inactivating
      host defenses.

PMID- 18614638
TI  - Influenza A virus matrix protein 1-specific human CD8+ T-cell response induced in
      trivalent inactivated vaccine recipients.
AB  - Among 17 HLA-A2-positive healthy adults, CD8+ T-cell responses against an HLA-A2
      restricted matrix protein 1 (M1) epitope increased after immunization with
      trivalent inactivated influenza vaccine (TIV) in two individuals. The presence of
      M1 in TIV was confirmed by Western blotting. T-cell cytotoxicity assays showed
      that TIV is processed and the epitope is presented by antigen-presenting cells to
      an M1 epitope-specific CD8+ T-cell line for specific lysis. These data show that
      TIV, which is formulated to contain surface glycoproteins to induce serotype
      specific antibody responses, also contains M1, capable of inducing subtype cross
      reactive CD8+ T-cell responses in some vaccinees.

PMID- 18614639
TI  - Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola
      mediated endocytosis.
AB  - Foot-and-mouth disease virus (FMDV) utilizes different cell surface
      macromolecules to facilitate infection of cultured cells. Virus, which is
      virulent for susceptible animals, infects cells via four members of the alpha(V)
      subclass of cellular integrins. In contrast, tissue culture adaptation of some
      FMDV serotypes results in the loss of viral virulence in the animal, accompanied
      by the loss of virus' ability to use integrins as receptors. These avirulent
      viral variants acquire positively charged amino acids on surface-exposed
      structural proteins, resulting in the utilization of cell surface heparan sulfate
      (HS) molecules as receptors. We have recently shown that FMDV serotypes utilizing
      integrin receptors enter cells via a clathrin-mediated mechanism into early
      endosomes. Acidification within the endosome results in a breakdown of the viral
      capsid, releasing the RNA, which enters the cytoplasm by a still undefined
      mechanism. Since there is evidence that HS internalizes bound ligands via a
      caveola-mediated mechanism, it was of interest to analyze the entry of FMDV by
      cell-surface HS. Using a genetically engineered variant of type O(1)Campos
      (O(1)C3056R) which can utilize both integrins and HS as receptors and a second
      variant (O(1)C3056R-KGE) which can utilize only HS as a receptor, we followed
      viral entry using confocal microscopy. After virus bound to cells at 4 degrees C,
      followed by a temperature shift to 37 degrees C, type O(1)C3056R-KGE colocalized
      with caveolin-1, while O(1)C3056R colocalized with both clathrin and caveolin-1.
      Compounds which either disrupt or inhibit the formation of lipid rafts inhibited
      the replication of O(1)C3056R-KGE. Furthermore, a caveolin-1 knockdown by RNA
      interference also considerably reduced the efficiency of O(1)C3056R-KGE
      infection. These results indicate that HS-binding FMDV enters the cells via the
      caveola-mediated endocytosis pathway and that caveolae can associate and traffic
      with endosomes. In addition, these results further suggest that the route of FMDV
      entry into cells is a function solely of the viral receptor.

PMID- 18614640
TI  - Nontemplated terminal nucleotidyltransferase activity of double-stranded RNA
      bacteriophage phi6 RNA-dependent RNA polymerase.
AB  - The replication and transcription of double-stranded RNA (dsRNA) viruses occur
      within a polymerase complex particle in which the viral genome is enclosed
      throughout the entire life cycle of the virus. A single protein subunit in the
      polymerase complex is responsible for the template-dependent RNA polymerization
      activity. The isolated polymerase subunit of the dsRNA bacteriophage phi6 was
      previously shown to replicate and transcribe given RNA molecules. In this study,
      we show that this enzyme also catalyzes nontemplated nucleotide additions to
      single-stranded and double-stranded nucleic acid molecules. This terminal
      nucleotidyltransferase activity not only is a property of the isolated enzyme but
      also is detected to take place within the viral nucleocapsid. This is the first
      time terminal nucleotidyltransferase activity has been reported for a dsRNA virus
      as well as for a viral particle. The results obtained together with previous high
      resolution structural data on the phi6 RNA-dependent RNA polymerase suggest a
      mechanism for terminal nucleotidyl addition. We propose that the activity is
      involved in the termination of the template-dependent RNA polymerization reaction
      on the linear phi6 genome.

PMID- 18614641
TI  - Frequency and spectrum of genomic integration of recombinant adeno-associated
      virus serotype 8 vector in neonatal mouse liver.
AB  - Neonatal injection of recombinant adeno-associated virus serotype 8 (rAAV8)
      vectors results in widespread transduction in multiple organs and therefore holds
      promise in neonatal gene therapy. On the other hand, insertional mutagenesis
      causing liver cancer has been implicated in rAAV-mediated neonatal gene transfer.
      Here, to better understand rAAV integration in neonatal livers, we investigated
      the frequency and spectrum of genomic integration of rAAV8 vectors in the liver
      following intraperitoneal injection of 2.0 x 10(11) vector genomes at birth. This
      dose was sufficient to transduce a majority of hepatocytes in the neonatal
      period. In the first approach, we injected mice with a beta-galactosidase
      expressing vector at birth and quantified rAAV integration events by taking
      advantage of liver regeneration in a chronic hepatitis animal model and following
      partial hepatectomy. In the second approach, we performed a new, quantitative
      rAAV vector genome rescue assay by which we identified rAAV integration sites and
      quantified integrations. As a result, we find that at least approximately 0.05%
      of hepatocytes contained rAAV integration, while the average copy number of
      integrated double-stranded vector genome per cell in the liver was approximately
      0.2, suggesting concatemer integration. Twenty-three of 34 integrations (68%)
      occurred in genes, but none of them were near the mir-341 locus, the common rAAV
      integration site found in mouse hepatocellular carcinoma. Thus, rAAV8 vector
      integration occurs preferentially in genes at a frequency of 1 in approximately
      10(3) hepatocytes when a majority of hepatocytes are once transduced in the
      neonatal period. Further studies are warranted to elucidate the relationship
      between vector dose and integration frequency or spectrum.

PMID- 18614642
TI  - Presence of the adenovirus IVa2 protein at a single vertex of the mature virion.
AB  - Assembly of adenovirus particles is thought to be similar to that of
      bacteriophages, in which the double-stranded DNA genome is inserted into a
      preformed empty capsid. Previous studies from our and other laboratories have
      implicated the viral IVa2 protein as a key component of the encapsidation
      process. IVa2 binds to the packaging sequence on the viral chromosome in a
      sequence-specific manner, alone and in conjunction with the viral L4 22K protein.
      In addition, it interacts with the viral L1 52/55-kDa protein, which is required
      for DNA packaging. Finally, a mutant virus that does not produce IVa2 is unable
      to produce any capsids. Therefore, it has been proposed that IVa2 nucleates
      capsid assembly. A prediction of such a model is that the IVa2 protein would be
      found at a unique vertex of the mature virion. In this study, the location of
      IVa2 in the virion has been analyzed using immunogold staining and electron
      microscopy, and the copy number of IVa2 in virions was determined using three
      independent methods, quantitative mass spectrometry, metabolic labeling, and
      Western blotting. The results indicate that it resides at a unique vertex and
      that there are approximately six to eight IVa2 molecules in each particle. These
      findings support the hypothesis that the IVa2 protein plays multiple roles in the
      viral assembly process.

PMID- 18614643
TI  - Importance of NKT cells in resistance to herpes simplex virus, fate of virus
      infected neurons, and level of latency in mice.
AB  - Herpes simplex virus type 1 (HSV-1) produces acute mucocutaneous infections,
      spread to sensory ganglia, and establishment of latency. In addition,
      neurovirulent strains have potential to invade the central nervous system (CNS),
      with potentially a lethal outcome. Early activation of defenses at all stages is
      essential to limit virus load and reduce the risk of neuronal damage, extensive
      zosteriform skin lesions, and catastrophic spread to the CNS. NKT cells respond
      rapidly, and we have shown previously that CD1d-deficient mice are compromised in
      controlling a neuroinvasive isolate of HSV-1. We now compare infection in
      Jalpha18 GKO and CD1d GKO mice, allowing direct assessment of the importance of
      invariant Valpha14(+) NKT cells and deduction of the role of the CD1d-restricted
      NKT cells with diverse T-cell receptors. The results indicate that both subsets
      of NKT cells contribute to virus control both in the afferent phase of infection
      and in determining the mortality, neuroinvasion, loss of sensory neurons, size of
      zosteriform, lesions and levels of latency. In particular, both are crucial
      determinants of clinical outcome, providing protection equivalent to a 1-log dose
      of virus. These NKT cells can be expected to provide protection at doses of virus
      that might be encountered naturally.

PMID- 18614644
TI  - Immune response in the absence of neurovirulence in mice infected with m protein
      mutant vesicular stomatitis virus.
AB  - Matrix (M) protein mutants of vesicular stomatitis virus (VSV), such as rM51R-M
      virus, are less virulent than wild-type (wt) VSV strains due to their inability
      to suppress innate immunity. Studies presented here show that when inoculated
      intranasally into mice, rM51R-M virus was cleared from nasal mucosa by day 2
      postinfection and was attenuated for spread to the central nervous system, in
      contrast to wt VSV, thus accounting for its reduced virulence. However, it
      stimulated an antibody response similar to that in mice infected with the wt
      virus, indicating that it has the ability to induce adaptive immunity in vivo
      without causing disease. These results support the use of M protein mutants of
      VSV as vaccine vectors.

PMID- 18614645
TI  - Novel genospecies of Borrelia burgdorferi sensu lato from rodents and ticks in
      southwestern China.
AB  - By using multilocus sequence analysis, five Borrelia valaisiana-related strains
      isolated from rodents and ticks in southwestern China were eventually classified
      as a new genospecies of B. burgdorferi sensu lato rather than B. valaisiana. The
      finding explained the differences in transmission cycle and phenotype between B.
      valaisiana strains from Europe and B. valaisiana-related strains from eastern
      Asia.

PMID- 18614646
TI  - MVPlex assay for direct detection of methicillin-resistant Staphylococcus aureus
      in naris and other swab specimens.
AB  - We evaluated the MVPlex assay (Geneco Biomedical Products), which uses target
      enriched multiplex PCR amplification followed by liquid array identification, for
      the detection of methicillin-resistant Staphylococcus aureus (MRSA) from 307 dual
      swab specimens. By using a combination of culture (Trypticase soy agar-5% sheep
      blood agar and Columbia CNA agar-5% sheep blood) and an FDA-approved MRSA PCR
      assay as the "gold standard," the MVPlex MRSA assay and culture were found to
      have sensitivities of 97.8% and 84.4% (P = 0.002) and specificities of 95.8% and
      98.6% (P < 0.05), respectively.

PMID- 18614647
TI  - Comparison of conventional, nested, and real-time PCR assays for rapid and
      accurate detection of Vibrio vulnificus.
AB  - We conducted a prospective study to target toxR in the blood of patients with
      skin and soft tissue infections who were admitted to four tertiary hospitals to
      assess the clinical usefulness of real-time quantitative PCR (Q-PCR) as a
      diagnostic technique. We performed conventional PCR (C-PCR), nested PCR (N-PCR),
      and Q-PCR assays and compared the results to those obtained using the "gold
      standard" of microbiological culture. The lower detection limit for the Q-PCR
      assay was 5 x 10(0) copies/microl. By use of blood samples of patients with skin
      and soft tissue infections, the sensitivities of the C-PCR and N-PCR assays
      against the target toxR gene of V. vulnificus as diagnostic tools were determined
      to be 45% and 86%, respectively. The C-PCR and N-PCR assays had specificities of
      100% and 73%, respectively. When we adopted a crossing-point (cp) cutoff value of
      <38 cp as a positive result, the Q-PCR assay had 100% sensitivity and
      specificity. Q-PCR to detect V. vulnificus-specific genes is not only the most
      sensitive and specific of the techniques but also the most rapid diagnostic
      method. Therefore, the appropriate application of the Q-PCR assay using blood is
      useful for the rapid diagnosis and subsequent treatment of V. vulnificus sepsis.

PMID- 18614648
TI  - Viability of Trichomonas vaginalis in Copan universal transport medium and eSwab
      transport medium.
AB  - We compared the use of universal transport medium and eSwab transport medium held
      at room temperature or 37 degrees C to bedside inoculation and immediate
      incubation of culture media for the detection of Trichomonas vaginalis. There
      were no significant culturable differences in the sensitivity of either of the
      transport media to that of bedside inoculation.

PMID- 18614649
TI  - Pharmacoeconomic analysis of microbiologic techniques for differentiating
      staphylococci directly from blood culture bottles.
AB  - Differentiating staphylococci in blood cultures is a critical issue, particularly
      when only one of two cultures is positive by Gram staining for staphylococci. New
      tests for the identification of Staphylococcus aureus allow faster results and
      definitive treatment compared to the tube coagulase test interpreted at 24 h
      (TCT24). These newer tests, peptide nucleic acid fluorescence in situ
      hybridization (PNA-FISH) and real-time PCR (RT-PCR), offer improved sensitivity
      at higher cost. Data suggest that the tube coagulase test may be interpreted at 4
      h (TCT4) with little loss of sensitivity. The impact of variability in turnaround
      time, sensitivity, specificity, and cost on comparative cost-effectiveness is
      unknown. Our aim was to establish the cost-effectiveness of TCT24, PNA-FISH, RT
      PCR, and TCT4 for direct identification of staphylococci in blood cultures.
      Decision analysis comparing these strategies was done from the institutional
      perspective. Besides test variables, other variables included patient risk
      factors, empirical treatment, and follow-up cultures. Probability and cost
      estimates came from the literature and institutional data. Base case estimates
      were derived from institutional rates of 73% contamination when coagulase
      negative staphylococci were identified, 67.6% prevalence of risk factors, and
      12.4% prevalence of S. aureus when one of two cultures yielded staphylococci.
      Sensitivity analysis was done across a range of probabilities and costs. In the
      base case, TCT4 and TCT24 were more cost-effective than RT-PCR and PNA-FISH ($78
      versus $120 versus $165 per patient, respectively). The advantage of TCT4 and
      TCT24 remained robust upon sensitivity analysis. TCT4 should be further evaluated
      as a rapid, cost-effective means for identification of S. aureus in blood
      cultures.

PMID- 18614650
TI  - Sensitivities of nasal and rectal swabs for detection of methicillin-resistant
      Staphylococcus aureus colonization in an active surveillance program.
AB  - All medical and high-risk surgical patients were screened for methicillin
      resistant Staphylococcus aureus colonization over 3.5 years. The sensitivities of
      nasal and rectal swabs were 68% and 62%, respectively. Naris and open-skin-site
      swabs detected 467 (74%) of 627 adult carriers identified. Rectal swabs detected
      an additional 160 (26%) carriers.

PMID- 18614651
TI  - Utility of new 24-locus variable-number tandem-repeat typing for discriminating
      Mycobacterium tuberculosis clinical isolates collected in Bulgaria.
AB  - The present study evaluated new markers for molecular typing of Mycobacterium
      tuberculosis with a collection of strains circulating in Bulgaria. A study sample
      included 133 strains from epidemiologically unlinked patients from different
      regions of the country. Spoligotyping was used as a primary typing tool; it
      subdivided these strains into 37 types, including 15 clusters and 22 singletons.
      Traditional IS6110-restriction fragment length polymorphism (RFLP) typing and
      novel 24-locus variable number tandem-repeat (VNTR) typing methods were applied
      to the selection of 73 strains. Discriminatory power (Hunter-Gaston index [HGI])
      of these methods was found to be 0.983 and 0.997, respectively. The 73 strains
      were subdivided into 66 types by a 24-locus mycobacterial interspersed repetitive
      unit (MIRU)-VNTR scheme, 62 types by a classical 12-locus MIRU-VNTR scheme, 51
      types by IS6110-RFLP typing, and 31 types by spoligotyping. A combination of the
      five most polymorphic loci (MIRU40, Mtub04, Mtub21, QUB-11b, and QUB-26) was
      shown to achieve a high discrimination (HGI = 0.984). To conclude, a complete 24
      locus scheme excellently differentiated strains in our study, whereas a reduced 5
      locus set provided a sufficiently high differentiation and may be preliminarily
      suggested for the first-line typing of M. tuberculosis isolates in Bulgaria.

PMID- 18614652
TI  - Internally controlled triplex quantitative PCR assay for human polyomaviruses JC
      and BK.
AB  - We have developed a triplex TaqMan-based quantitative PCR assay for the human
      polyomaviruses JC (JCPyV) and BK (BKPyV). The assay simultaneously detects and
      quantifies both JCPyV and BKPyV in human clinical samples, and it includes an
      internal amplification control consisting of murine polyomavirus (MuPyV) plasmid
      DNA. We developed the assay for the Roche LightCycler 480 platform with the
      reporter dyes VIC, 6-FAM, and Cy5 for MuPyV, BKPyV, and JCPyV, respectively. The
      assay had a high specificity for BKPyV and JCPyV when either viral genome was
      present alone or in mixed samples over a range of 10(1) to 10(7) copy numbers per
      reaction. The analytical sensitivity was 50 copies for BKPyV and 10 copies for
      JCPyV. The use of the MuPyV internal control ensured monitoring of the quality of
      the extraction and of PCR inhibition, even in samples such as cerebrospinal fluid
      and plasma in which controls based on host genes cannot be effectively used. In
      addition, we developed a similar assay using a different dye configuration (6
      FAM, VIC, and NED) that could be used on an ABI 7500 Fast platform. This assay
      had sensitivities similar to those of the LightCycler 480 configuration for BKPyV
      and JCPyV when either viral genome was present alone, but the sensitivity of
      detection of BKPyV was greatly decreased when an excess of JCPyV (>100-fold) was
      present in the sample. This internally controlled combined assay offers greater
      convenience and cost-effectiveness compared to separate assays for each virus and
      can also detect unexpected PyV activations by testing for both viruses in all
      samples.

PMID- 18614653
TI  - Prevalence of human parechovirus in the Netherlands in 2000 to 2007.
AB  - Infection with human parechovirus 3 (HPeV3) was described for the first time in
      Japan in 2004 and reportedly is more often associated with severe disease than
      infection with HPeV1 or HPeV2. In 2004, infections with HPeV3 were observed for
      the first time in The Netherlands. Genetic analysis showed several different
      lineages, suggesting endemic circulation. We analyzed 163 cell culture isolates
      from the same number of patients tested in routine virological laboratories as
      part of the national enterovirus surveillance program. Isolates were collected
      between 2000 and 2007 and could not be characterized by routine methods. In
      total, 155 isolates (95%) were found positive for HPeV by a reverse transcription
      PCR assay targeting the 5' untranslated region, explaining the majority of the
      diagnostic deficit in enterovirus surveillance for these years. Typing of the
      isolates by use of partial genome sequencing of the VP1/2A region revealed the
      presence of 55 HPeV1, 2 HPeV2, 89 HPeV3, 1 HPeV4, and 8 HPeV5 isolates. We
      compared isolation dates, age groups affected, and clinical pictures, which were
      reported as part of the routine surveillance. Clear differences in epidemiology
      were observed, with HPeV3 occurring at intervals of 2 years and in the spring
      summer season, whereas HPeV1 was observed in small numbers throughout each year,
      with a low in the summer months. HPeV3 infection affected younger children than
      HPeV1 infection and was significantly more often associated with fever,
      meningitis, and viremia.

PMID- 18614654
TI  - Molecular epidemiology of methicillin-resistant and methicillin-susceptible
      Staphylococcus aureus isolates from global clinical trials.
AB  - Determining the genetic characteristics of Staphylococcus aureus is important for
      better understanding of the global and dynamic epidemiology of this organism as
      we witness the emergence and spread of virulent and antibiotic-resistant clones.
      We genotyped 292 S. aureus isolates (105 methicillin resistant and 187
      methicillin susceptible) using a combination of pulsed-field gel electrophoresis,
      multilocus sequence typing, and SCCmec typing. In addition, S. aureus isolates
      were tested for the presence of the Panton-Valentine leukocidin (PVL) genes.
      Isolates were recovered from patients with uncomplicated skin infections in 10
      different countries during five phase III global clinical trials of retapamulin,
      a new topical antibiotic agent. The most common methicillin-resistant clone had
      multilocus sequence type 8, pulsed-field type USA300, and SCCmec type IV and
      possessed the PVL genes. This clone was isolated exclusively in the United
      States. The most common PVL-positive, methicillin-susceptible clone had
      multilocus sequence type 121 and pulsed-field type USA1200. This clone was found
      primarily in South Africa and the Russian Federation. Other clones were found at
      lower frequencies and were limited in their geographic distribution. Overall,
      considerable genetic diversity was observed within multilocus sequence type
      clonal complexes and pulsed-field types.

PMID- 18614655
TI  - Comprehensive study of strains previously designated Streptococcus bovis
      consecutively isolated from human blood cultures and emended description of
      Streptococcus gallolyticus and Streptococcus infantarius subsp. coli.
AB  - Modern taxonomy has delineated Streptococcus gallolyticus subsp. gallolyticus, S.
      gallolyticus subsp. pasteurianus, Streptococcus infantarius subsp. coli, and S.
      infantarius subsp. infantarius within the heterogenous group of previously
      designated clinical Streptococcus bovis bacteria. In the present study, 58
      consecutive blood culture isolates initially designated S. bovis were further
      characterized by applying phenotypic and molecular genetic methods, and possible
      disease associations were investigated by studying the patients' records.
      Published phenotypic characteristics of S. gallolyticus and S. infantarius were
      not unequivocal and did not allow an unambiguous phenotypic differentiation of
      the 58 clinical isolates. However, full-length 16S rRNA gene sequences clearly
      assigned the strains to S. gallolyticus subsp. gallolyticus (n = 29), S.
      gallolyticus subsp. pasteurianus (n = 12), and S. infantarius subsp. coli (n =
      17). Only 28% of the patients with available records presented with endocarditis
      and 7% presented with colon carcinoma, whereas 37% of the patients had altered
      liver parenchyma and 28% had gall bladder disease as underlying diseases.
      Detailed antimicrobial susceptibility data on both S. gallolyticus subspecies and
      S. infantarius subsp. coli are given for the first time. As a result of the
      extensive characterization of the largest number of S. gallolyticus and S.
      infantarius human clinical isolates published so far, emended species
      descriptions are given. It is recommended that both clinical microbiologists and
      infectious disease specialists avoid the designation S. bovis for true S.
      gallolyticus and S. infantarius strains in the future in order to get a clearer
      picture of the possible disease associations of these species.

PMID- 18614656
TI  - Contamination of the hospital environment with gastroenteric viruses: comparison
      of two pediatric wards over a winter season.
AB  - The aims of this study were to examine the extent of gastroenteric virus
      contamination in a pediatric primary immunodeficiency (PPI) ward and a general
      pediatric ward over a winter season and to determine whether changes to hospital
      infection control interventions would have an impact on environmental
      contamination levels within pediatric units. Environmental swabs were collected
      weekly from 11 sites in both wards from 15 December 2005 to 3 March 2006 and
      examined for the presence of norovirus (NoV), astrovirus, and rotavirus (RV) by
      reverse transcriptase PCR. Viruses were detected in 17% and 19% of swabs from
      both wards. Virus contamination for NoV and RV decreased from 20% to 6% and 15%
      to 10% of swabs, respectively, in the PPI ward from the 2004 study by Gallimore
      et al. (C. I. Gallimore, C. Taylor, A. R. Gennery, A. J. Cant, A. Galloway, M.
      Iturriza-Gomara, and J. J. Gray, J. Clin. Microbiol. 44:395-399, 2006). Overall,
      changes to cleaning protocols were deemed to have reduced the level of
      environmental contamination with gastroenteric viruses, but contamination still
      occurred due to a breakdown in infection control procedures indicated by
      contamination in areas frequented by parents but used only occasionally by staff.

PMID- 18614657
TI  - Rapid detection of blaKPC carbapenemase genes by real-time PCR.
AB  - Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide.
      Klebsiella pneumoniae carbapenemase (bla(KPC)) enzymes are among the most common
      beta-lactamases described. In this study, we report the development and
      validation of a real-time PCR (q-PCR) assay for the detection of bla(KPC) genes
      using TaqMan chemistry. The q-PCR amplification of bla(KPC) DNA was linear over 7
      log dilutions (r(2) = 0.999; slope, 3.54), and the amplification efficiency was
      91.6%. The q-PCR detection limit was 1 CFU, and there was no cross-reaction with
      DNA extracted from several multidrug-resistant bacteria. Perianal/rectal swabs (n
      = 187) collected in duplicate from 128 patients admitted to Sheba Medical Center
      surgical intensive care units were evaluated for the presence of carbapenem
      resistant bacteria by culturing on MacConkey agar-plus-carbapenem disks and for
      bla(KPC) genes by q-PCR. Carbapenem-resistant organisms, all K. pneumoniae, were
      isolated from 47 (25.1%) of the 187 samples collected, while bla(KPC) genes were
      detected in 54 (28.9%) of the patient samples extracted by the NucliSENS easyMAG
      system. Of these, seven samples were positive for bla(KPC) genes by q-PCR but
      negative for carbapenem resistance by culture, while all samples in which no
      carbapenem-resistant bacteria were detected by culture also tested negative by q
      PCR. Thus, the sensitivity and specificity of the q-PCR assay after extraction by
      the NucliSENS easyMAG system were 100% and 95%, respectively. Similar values were
      obtained after DNA extraction by the Roche MagNA Pure LC instrument: 97.9%
      sensitivity and 96.4% specificity. Overall, the bla(KPC) q-PCR assay appears to
      be highly sensitive and specific. The utilization of q-PCR will shorten the time
      to bla(KPC) detection from 24 h to 4 h and will help in rapidly isolating
      colonized or infected patients and assigning them to cohorts.

PMID- 18614658
TI  - Kocuria rhizophila adds to the emerging spectrum of micrococcal species involved
      in human infections.
AB  - We describe the first case of a Kocuria rhizophila infection in a boy with
      methylmalonic aciduria. A single clone was isolated from blood samples drawn
      through a port system and from peripheral veins during septic episodes within a 2
      year period. K. rhizophila expands the emerging number of "micrococci" considered
      to be etiologically relevant.

PMID- 18614659
TI  - Molecular diagnosis of Old World cutaneous leishmaniasis and species
      identification by use of a reverse line blot hybridization assay.
AB  - Reverse line blot hybridization assays (RLB) have been used for the rapid
      diagnosis and genotyping of many pathogens. The leishmaniases are caused by a
      large number of species, and rapid, accurate parasite characterization is
      important in deciding on appropriate therapy. Fourteen oligonucleotide probes, 2
      genus specific and 12 species specific (2 specific for Leishmania major, 3 for L.
      tropica, 1 for L. infantum, 3 for L. donovani, and 3 for L. aethiopica), were
      prepared by using DNA sequences in the internal transcribed spacer 1 (ITS1)
      region of the rRNA genes. Probe specificity was evaluated by amplifying DNA from
      21 reference strains using biotinylated ITS1 PCR primers and the RLB. The genus
      specific probes, PP and PP3', recognized all Leishmania species examined, while
      the species-specific probes were able to distinguish between all the Old World
      Leishmania species. Titrations using purified parasite DNA showed that the RLB is
      10- to 100-fold more sensitive than ITS1 PCR and can detect <0.1 pg DNA. The RLB
      was compared to kinetoplast DNA (kDNA) and ITS1 PCR by using 67 samples from
      suspected cutaneous leishmaniasis (CL) patients in Israel and the West Bank. The
      RLB accurately identified 58/59 confirmed positive samples as CL, a result
      similar to that found by kDNA PCR (59/59) and better than that by ITS1 PCR
      (50/59). The positive predictive value and negative predictive value of the RLB
      were 95.1% and 83.3%, respectively. L. major or L. tropica was identified by the
      RLB in 55 of the confirmed positive cases, a level of accuracy better than that
      of ITS1 PCR with restriction fragment length polymorphism (42/59). Thus, RLB can
      be used to diagnose and characterize Old World CL.

PMID- 18614660
TI  - Diminished human immunodeficiency virus type 1 DNA yield from dried blood spots
      after storage in a humid incubator at 37 degrees C compared to -20 degrees C.
AB  - Collecting whole blood on filter paper simplifies the processing, transport, and
      storage of specimens used for the diagnosis of human immunodeficiency virus type
      1 (HIV-1) and other tests. Specimens may be collected in tropical or rural areas
      with minimal facilities for handling specimens. To compare simulated tropical
      conditions with freezer storage, we examined the stability of HIV-1 DNA in dried
      blood spots (DBS) stored in humid heat and at -20 degrees C. DBS were created by
      spotting 50-microl aliquots of whole blood on 903 filter paper. DNA was extracted
      from DBS at baseline and after 2, 6, or 12 months of storage at -20 degrees C or
      at 37 degrees C with approximately 85% humidity. The DNA was tested undiluted or
      diluted using the Amplicor HIV-1 DNA PCR (Roche), version 1.5. Each reaction was
      scored positive, negative, or indeterminate based on optical density. Results
      were compared between storage conditions and over time. A total of 1,832
      reactions from 916 DBS were analyzed, including 100 DBS at baseline, 418 stored
      at -20 degrees C, and 398 stored at 37 degrees C. A chi-square test showed fewer
      positive reactions for DBS stored at 37 degrees C (55%) than for those stored at 
      20 degrees C (78%) (P < 0.0001). Samples stored at -20 degrees C showed little
      change in the probability of detection of HIV-1 DNA over time; the odds ratio
      (OR) was 0.93 after storage for 1 year. Samples stored at 37 degrees C
      demonstrated a significant change in detection at 1 year (OR, 0.29). We conclude
      that exposure of DBS to 37 degrees C and high humidity impaired the recovery of
      HIV-1 DNA from DBS, whereas DNA recovery was preserved when DBS were stored
      frozen.

PMID- 18614661
TI  - Comparative study of nasopharyngeal aspirate and nasal swab specimens for
      diagnosis of acute viral respiratory infection.
AB  - Paired nasopharyngeal aspirate (NPA) and nasal swab (NS) samples from 475
      children hospitalized for acute respiratory infection were studied for the
      detection of influenza virus, parainfluenza virus, respiratory syncytial virus,
      and adenovirus by immunofluorescence test, viral culture, and multiplex PCR
      assay. The overall sensitivity of viral detection with NPA specimens was higher
      than that obtained with NS specimens.

PMID- 18614662
TI  - Countrywide molecular survey of methicillin-resistant Staphylococcus aureus
      strains in Poland.
AB  - The present investigation was undertaken to assess the proportion of methicillin
      resistant Staphylococcus aureus (MRSA) strains among hospital-acquired isolates
      and to determine the clones of MRSA currently circulating in Poland by using a
      number of molecular techniques. Between January and May 2005, methicillin
      resistance was investigated among a total of 915 S. aureus isolates collected
      from 39 hospitals. A total of 208 (22.7%) isolates were positive for the mecA
      gene by PCR. The molecular characterization of MRSA isolates was carried out by
      the multiple-locus variable-number tandem repeat fingerprinting, pulsed-field gel
      electrophoresis, multilocus sequence typing, and staphylococcal chromosomal
      cassette mec (SCCmec) typing methods. The Hungarian (PFGE B; ST239, SCCmec type
      III [ST239-III]), Iberian (ST247-I), and Berlin (ST45-IV) clones were
      predominant, representing approximately 52.9, 11.5, and 10.0% of the MRSA
      isolates, respectively. A decline in the proportion of earlier MRSA clones, such
      as ST5-IV (a Pediatric clone), ST80-IV) (a Mediterranean clone), ST239-III (a
      Polish and Brazilian clone), and ST30-IV (a southwest Pacific clone) was
      observed. Additionally, the emergence of an MRSA clone with SCCmec type V,
      possibly representing a community-acquired strain, was observed in two hospitals
      during this study.

PMID- 18614663
TI  - Evaluation of three real-time PCR assays for detection of Mycoplasma pneumoniae
      in an outbreak investigation.
AB  - We compared the performances of three recently optimized real-time PCR assays
      derived from distinct genomic regions of Mycoplasma pneumoniae during an
      outbreak. Comprehensive evaluation established that a newly described toxin gene
      represents a superior target for detecting M. pneumoniae DNA in clinical
      specimens, although use of multiple targets may increase testing confidence.

PMID- 18614664
TI  - Changing patterns in frequency of recovery of five methicillin-resistant
      Staphylococcus aureus clones in Portuguese hospitals: surveillance over a 16-year
      period.
AB  - A total of 629 nonduplicate methicillin-resistant Staphylococcus aureus MRSA
      isolates were recovered between June and November 2006 from 11 hospitals located
      in different areas of Portugal. Selected isolates (n = 271, 43%) were typed by
      pulsed-field gel electrophoresis (PFGE), representatives of which were
      additionally characterized by spa typing, multilocus sequence typing,
      staphylococcal cassette chromosome mec (SCCmec) typing, and the presence of
      Panton-Valentine leukocidin (PVL). The 271 isolates were classified into 13
      different clonal types. Three pandemic clones included the majority (n = 241,
      88%) of the isolates and were observed in several hospitals: (i) EMRSA-15 (54%)
      PFGE type A, ST22, spa type t022, SCCmec IV-was found in the 11 hospitals studied
      and was identified as the major clone in seven of them; (ii) the New York/Japan
      clone (17%)-PFGE B, ST5, spa type t067, SCCmec II-was identified in nine
      hospitals and represented the major clone in four; and (iii) the Brazilian MRSA
      (17%)-PFGE C, ST239, spa type t037, SCCmec IIIA-was also detected in nine
      hospitals but never as the main clone. All isolates tested were PVL negative.
      Clone EMRSA-15 is currently the predominant MRSA clonal type circulating in
      Portuguese hospitals, but a new wave of MRSA has emerged in the country with the
      recent introduction and spread of the New York/Japan clone. The Brazilian MRSA
      that was the leading clone in Portugal in the late 1990s is declining and being
      progressively replaced by the two former clones. We report the first isolate
      SCCmec type V (ST45) in Portugal.

PMID- 18614665
TI  - New Erwinia-like organism causing cervical lymphadenitis.
AB  - The first case of cervical lymphadenitis due to infection by a new Erwinia-like
      organism is reported. The organism was identified initially as Pantoea sp. by a
      Vitek 2-based assessment but was finally identified as a member of the genus
      Erwinia by 16S rRNA gene sequence analysis. The isolate displayed 98.9% 16S rRNA
      gene sequence similarity to that of E. tasmaniensis and showed phenotypic
      characteristics that were different from other Erwinia species.

PMID- 18614666
TI  - Nocardia cyriacigeorgica--an established rather than an emerging pathogen.

PMID- 18614667
TI  - Clinical rationale for treatment of endocarditis caused by methicillin
      susceptible Staphylococcus aureus developing nonsusceptibility to daptomycin.

PMID- 18614668
TI  - Neisseria meningitidis PorB, a Toll-like receptor 2 ligand, improves the capacity
      of Francisella tularensis lipopolysaccharide to protect mice against experimental
      tularemia.
AB  - Francisella tularensis causes severe pneumonia that can be fatal if it is left
      untreated. Due to its potential use as a biological weapon, research is being
      conducted to develop an effective vaccine and to select and study adjuvant
      molecules able to generate a better and long-lasting protective effect. PorB, a
      porin from Neisseria meningitidis, is a well-established Toll-like receptor 2
      ligand and has been shown to be a promising vaccine adjuvant candidate due to its
      ability to enhance the T-cell costimulatory activity of antigen-presenting cells
      both in vitro and in vivo. BALB/c mice were immunized with lipopolysaccharide
      (LPS) isolated from the F. tularensis subsp. holarctica live vaccine strain
      (LVS), with or without PorB from N. meningitidis, and the antibody levels induced
      during the vaccination regimen and the level of protection against intranasal
      challenge with LVS were determined. Antigen administered alone induced a specific
      F. tularensis LPS immunoglobulin M (IgM) response that was not maintained over
      the weeks and that conferred protection to only 25% of the mice. In contrast, F.
      tularensis LPS given in combination with neisserial PorB induced consistent
      levels of specific IgM throughout the immunization and increased the proportion
      of surviving mice to 70%. Postchallenge cytokine analysis showed that interleukin
      6 (IL-6), monocyte chemoattractant protein 1, and gamma interferon were markers
      of mortality and that IL-1beta was a correlate of survival, independent of the
      presence of PorB as an adjuvant. These data indicate that neisserial PorB might
      be an optimal candidate adjuvant for improving the protective effect of F.
      tularensis LPS and other subunit vaccines against tularemia, but there is still a
      need to test its efficacy against virulent type A and type B F. tularensis
      strains.

PMID- 18614669
TI  - A FLEX switch targets Channelrhodopsin-2 to multiple cell types for imaging and
      long-range circuit mapping.

PMID- 18614670
TI  - Training-induced brain structure changes in the elderly.
AB  - It has been suggested that learning is associated with a transient and highly
      selective increase in brain gray matter in healthy young volunteers. It is not
      clear whether and to what extent the aging brain is still able to exhibit such
      structural plasticity. We built on our original study, now focusing on healthy
      senior citizens. We observed that elderly persons were able to learn three-ball
      cascade juggling, but with less proficiency compared with 20-year-old
      adolescents. Similar to the young group, gray-matter changes in the older brain
      related to skill acquisition were observed in area hMT/V5 (middle temporal area
      of the visual cortex). In addition, elderly volunteers who learned to juggle
      showed transient increases in gray matter in the hippocampus on the left side and
      in the nucleus accumbens bilaterally.

PMID- 18614671
TI  - Emotion-induced retrograde amnesia is determined by a 5-HTT genetic polymorphism.
AB  - A polymorphism in the human serotonin transporter (5-HTT) gene is implicated in
      susceptibility to anxiety and depression and in enhanced emotion-induced
      activation in the amygdala. A role for 5-HTT polymorphism in the emotional
      modulation of human episodic memory has yet to be demonstrated. Here, we
      demonstrate that whereas emotional memory for aversive events per se is not
      influenced by 5-HTT polymorphism, an emotion-induced retrograde amnesia is
      expressed solely in the presence of the short allele. The findings indicate a
      critical role for the serotonin system in emotion-mediated memory disruption.

PMID- 18614672
TI  - Anomalous dopamine release associated with a human dopamine transporter coding
      variant.
AB  - Dopamine (DA) signaling at synapses is tightly coordinated through opposing
      mechanisms of vesicular fusion-mediated DA release and transporter-mediated DA
      clearance. Altered brain DA signaling is suspected to underlie multiple brain
      disorders, including schizophrenia, Parkinson's disease, bipolar disorder, and
      attention-deficit hyperactivity disorder (ADHD). We identified a pedigree
      containing two male children diagnosed with ADHD who share a rare human DA
      transporter (DAT; SLC6A3) coding variant, Ala559Val. Among >1000 control and
      affected subjects, the Val559 variant has only been isolated once previously, in
      a female subject with bipolar disorder. Although hDAT Ala559Val supports normal
      DAT protein and cell surface expression, as well as normal DA uptake, the variant
      exhibits anomalous DA efflux from DA-loaded cells. We also demonstrate that hDAT
      Ala599Val exhibits increased sensitivity to intracellular Na(+), but not
      intracellular DA, and displays exaggerated DA efflux at depolarized potentials.
      Remarkably, the two most common ADHD medications, amphetamine and
      methylphenidate, both block hDAT Ala559Val-mediated DA efflux, whereas these
      drugs have opposite actions at wild-type hDAT. Our findings reveal that DA
      efflux, typically associated with amphetamine-like psychostimulants, can be
      produced through a heritable change in hDAT structure. Because multiple gene
      products are known to coordinate to support amphetamine-mediated DA efflux, the
      properties of hDAT Ala559Val may have broader significance in identifying a new
      mechanism through which DA signaling disorders arise. Additionally, they suggest
      that block of inappropriate neurotransmitter efflux may be an unsuspected
      mechanism supporting the therapeutic actions of existing transporter-directed
      medications.

PMID- 18614673
TI  - Erbin controls dendritic morphogenesis by regulating localization of delta
      catenin.
AB  - The LAP [leucine-rich and postsynaptic density-95/Discs large/zona occludens-1
      (PDZ)] protein erbin and delta-catenin, a component of the cadherin-catenin cell
      adhesion complex, are highly expressed in neurons and associate through PDZ
      mediated interaction, but have incompletely characterized neuronal functions. We
      show that short hairpin RNA-mediated knockdown of erbin and knockdown or genetic
      ablation of delta-catenin severely impaired dendritic morphogenesis in
      hippocampal neurons. Simultaneous loss of erbin and delta-catenin does not
      enhance severity of this phenotype. The dendritic phenotype observed after erbin
      depletion is rescued by overexpression of delta-catenin and requires a domain in
      delta-catenin that has been shown to regulate dendritic branching. Knockdown of
      delta-catenin cannot be rescued by overexpression of erbin, indicating that erbin
      is upstream of delta-catenin. delta-Catenin-null neurons have no alterations in
      global levels of active Rac1/RhoA. Knockdown of erbin results in alterations in
      localization of delta-catenin. These results suggest a critical role for erbin in
      regulating dendritic morphogenesis by maintaining appropriate localization of
      delta-catenin.

PMID- 18614674
TI  - Bone morphogenetic proteins, eye patterning, and retinocollicular map formation
      in the mouse.
AB  - Patterning events during early eye formation determine retinal cell fate and can
      dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward
      central brain targets. The temporally and spatially regulated expression of bone
      morphogenetic proteins (BMPs) and their receptors in the retina are thought to
      play a key role in this process, initiating gene expression cascades that
      distinguish different regions of the retina, particularly along the dorsoventral
      axis. Here, we examine the role of BMP and a potential downstream effector, EphB,
      in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior
      colliculus (SC). RGC axon behaviors during retinotopic map formation in wild-type
      mice are compared with those in several strains of mice with engineered defects
      of BMP and EphB signaling. Normal RGC axon sorting produces axon order in the
      optic tract that reflects the dorsoventral position of the parent RGCs in the
      eye. A dramatic consequence of disrupting BMP signaling is a missorting of RGC
      axons as they exit the optic chiasm. This sorting is not dependent on EphB. When
      BMP signaling in the developing eye is genetically modified, RGC order in the
      optic tract and targeting in the LGN and SC are correspondingly disrupted. These
      experiments show that BMP signaling regulates dorsoventral RGC cell fate, RGC
      axon behavior in the ascending optic tract, and retinotopic map formation in the
      LGN and SC through mechanisms that are in part distinct from EphB signaling in
      the LGN and SC.

PMID- 18614675
TI  - P0 protein is required for and can induce formation of schmidt-lantermann
      incisures in myelin internodes.
AB  - Axons in the PNS and CNS are ensheathed by multiple layers of tightly compacted
      myelin membranes. A series of cytoplasmic channels connect outer and inner
      margins of PNS, but not CNS, myelin internodes. Membranes of these Schmidt
      Lantermann (S-L) incisures contain the myelin-associated glycoprotein (MAG) but
      not P(0) or proteolipid protein (PLP), the structural proteins of compact PNS
      (P(0)) and CNS (PLP) myelin. We show here that incisures are present in MAG-null
      and absent from P(0)-null PNS internodes. To test the possibility that P(0)
      regulates incisure formation, we replaced PLP with P(0) in CNS myelin. S-L
      incisures formed in P(0)-CNS myelin internodes. Furthermore, axoplasm ensheathed
      by 65% of the CNS incisures examined by electron microscopy had focal
      accumulations of organelles, indicating that these CNS incisures disrupt axonal
      transport. These data support the hypotheses that P(0) protein is required for
      and can induce S-L incisures and that P(0)-induced CNS incisures can be
      detrimental to axonal function.

PMID- 18614676
TI  - Roles of endocannabinoids in heterosynaptic long-term depression of excitatory
      synaptic transmission in visual cortex of young mice.
AB  - Tetanic stimulation of one of two afferent pathways converging to neurons in the
      visual cortex induces long-term depression (LTD) of synaptic transmission in the
      other, nonactivated pathway under a certain condition. This form of synaptic
      plasticity called heterosynaptic LTD (hetero-LTD) was not systematically
      investigated in previous studies, whereas homosynaptic LTD has been extensively
      studied. To determine whether hetero-LTD is induced in visual cortical slices of
      mice and, if so, through what mechanisms, we recorded EPSPs evoked in layer
      II/III neurons by alternating test stimulation of two sites in layer IV at 0.05
      Hz. After theta-burst stimulation of one site, EPSPs evoked by test stimulation
      of the other site were depressed for a long time in most of the neurons, whereas
      homosynaptic long-term potentiation was induced at activated synapses. Such a
      hetero-LTD was induced in most mice at postnatal day 7-20 (P7-P20), but not
      induced in mice at P35-P41. Tests using the paired-pulse stimulation protocol and
      coefficient of variation analysis suggested that hetero-LTD was expressed at
      presynaptic sites. Pharmacological analysis indicated that this form of LTD was
      induced through activation of the type 5 of metabotropic glutamate receptors, not
      through the NMDA type of glutamate receptors. Additional analysis using a
      cannabinoid type 1 receptor agonist and an antagonist suggested that
      endocannabinoids (eCBs) are involved in this type of LTD. Moreover, results
      suggest that brain-derived neurotrophic factor, which may be released from
      strongly activated presynaptic sites, prevents eCBs from suppressing the release
      of transmitters from these sites.

PMID- 18614677
TI  - Translocation of GluR1-containing AMPA receptors to a spinal nociceptive synapse
      during acute noxious stimulation.
AB  - Potentiation of spinal nociceptive transmission by synaptic delivery of AMPA
      receptors, via an NMDA receptor- and Ca(2+)/calmodulin-dependent protein kinase
      II (CaMKII)-dependent pathway, has been proposed to underlie certain forms of
      hyperalgesia, the enhanced pain sensitivity that may accompany inflammation or
      tissue injury. However, the specific synaptic populations that may be subject to
      such plasticity have not been identified. Using neuronal tracing and
      postembedding immunogold labeling, we show that a model of acute inflammatory
      hyperalgesia is associated with an elevated density of GluR1-containing AMPA
      receptors, as well as an increased synaptic ratio of GluR1 to GluR2/3 subunits,
      at synapses established by C-fibers that lack the neuropeptide substance P. A
      more subtle increase in GluR1 immunolabeling was noted at synapses formed by
      substance P-containing nociceptors. No changes in either GluR1 or GluR2/3
      contents were observed at synapses formed by low-threshold mechanosensitive
      primary afferent fibers. These results contrast with our previous observations in
      the same pain model of increased and decreased levels of activated CaMKII at
      synapses formed by peptidergic and nonpeptidergic nociceptive fibers,
      respectively, suggesting that the observed redistribution of AMPA receptor
      subunits does not depend on postsynaptic CaMKII activity. The present
      ultrastructural evidence of topographically specific, activity-dependent
      insertion of GluR1-containing AMPA receptors at a central synapse suggests that
      potentiation of nonpeptidergic C-fiber synapses by this mechanism contributes to
      inflammatory pain.

PMID- 18614678
TI  - Altered neuron excitability and synaptic plasticity in the cerebellar granular
      layer of juvenile prion protein knock-out mice with impaired motor control.
AB  - Although the role of abnormal prion protein (PrP) conformation in generating
      infectious brain diseases (transmissible spongiform encephalopathy) has been
      recognized, the function of PrP in the normal brain remains mostly unknown. In
      this investigation, we considered the effect of PrP gene knock-out (PrP(0/0)) on
      cerebellar neural circuits and in particular on granule cells, which show intense
      PrP expression during development and selective affinity for PrP. At the third
      postnatal week, when PrP expression would normally attain mature levels, PrP(0/0)
      mice showed low performance in the accelerating rotarod and runway tests and the
      functioning of 40% of granule cells was abnormal. Spikes were slow,
      nonovershooting, and nonrepetitive in relation with a reduction in transient
      inward and outward membrane currents, and also the EPSPs and EPSCs had slow
      kinetics. Overall, these alterations closely resembled an immature phenotype.
      Moreover, in slow-spiking PrP(0/0) granule cells, theta-burst stimulation was
      unable to induce any long-term potentiation. This profound impairment in synaptic
      excitation and plasticity was associated with a protracted proliferation of
      granule cells and disappeared at P40-P50 along with the recovery of normal motor
      behavior (Bueler et al., 1992). These results suggest that PrP plays an important
      role in granule cell development eventually regulating cerebellar network
      formation and motor control.

PMID- 18614679
TI  - Behavioral impact of neurotransmitter-activated G-protein-coupled receptors:
      muscarinic and GABAB receptors regulate Caenorhabditis elegans locomotion.
AB  - Neurotransmitter released from presynaptic terminals activates both ligand-gated
      ion channels (ionotropic receptors) and a variety of G-protein-coupled receptors
      (GPCRs). These neurotransmitter receptors are expressed on both presynaptic and
      postsynaptic cells. Thus, each neurotransmitter acts on multiple receptor
      classes, generating a large repertoire of physiological responses. The impact of
      many ionotropic receptors on neuronal activity and behavior has been clearly
      elucidated; however, much less is known about how neurotransmitter-gated GPCRs
      regulate neurons and circuits. In Caenorhabditis elegans, both acetylcholine
      (ACh) and GABA are released in the nerve cord and mediate fast neuromuscular
      excitation and inhibition during locomotion. Here we identify a muscarinic
      receptor (GAR-2) and the GABA(B) receptor dimer (GBB-1/2) that detect
      synaptically released ACh and GABA, respectively. Both GAR-2 and GBB-1/2
      inhibited cholinergic motor neurons when ACh and GABA levels were enhanced. Loss
      of either GPCR resulted in movement defects, suggesting that these receptors are
      activated during locomotion. When the negative feedback provided by GAR-2 was
      replaced with positive feedback, animals became highly sensitive to ACh levels
      and locomotion was severely impaired. Thus, conserved GPCRs act in the nematode
      motor circuit to provide negative feedback and to regulate locomotory behaviors
      that underlie navigation.

PMID- 18614680
TI  - Differences between dorsal and ventral striatum in Drd1a dopamine receptor
      coupling of dopamine- and cAMP-regulated phosphoprotein-32 to activation of
      extracellular signal-regulated kinase.
AB  - Dopamine receptor signaling exhibits prominent plasticity that is important for
      the pathogenesis of both addictive and movement disorders. Psychoactive
      stimulants that activate the dopamine D(1) receptor (Drd1a) induce the rapid
      phosphorylation and activation of extracellular signal-regulated kinase 1/2
      (ERK1/2) in neurons of the nucleus accumbens and ventral striatum. This response
      is known to be dependent on the phosphatase inhibitor dopamine- and cAMP
      regulated phosphoprotein-32 (DARPP-32) and appears critical for the sensitization
      of Drd1a responses that contributes to addiction. Loss of dopamine input to the
      striatum, as in models of Parkinson's disease (PD), also results in a
      sensitization of responses to dopamine agonists that is manifest by increased
      activation of ERK1/2 in the dorsal striatum. Here, we test whether DARPP-32 is
      required for sensitization of Drd1a responses in a PD model. In the normal dorsal
      striatum, there is minimal Drd1a-mediated activation of ERK1/2; however, in the
      PD model there is robust Drd1a-mediated activation of ERK1/2. In both wild-type
      and DARPP-32 knock-out mice, Drd1a robustly induces pERK1/2 throughout the
      dopamine-depleted striatum. These findings indicate that Drd1a sensitization
      relevant for PD occurs by a novel mechanism that does not require DARPP-32.

PMID- 18614681
TI  - A new Drosophila POU gene, pdm3, acts in odor receptor expression and axon
      targeting of olfactory neurons.
AB  - Olfaction depends on the differential activation of olfactory receptor neurons
      (ORNs) and on the proper transmission of their activities to the brain. ORNs
      select individual receptors to express, and they send axons to particular targets
      in the brain. Little is known about the molecular mechanisms underlying either
      process. We have identified a new Drosophila POU gene, pdm3, that is expressed in
      ORNs. Genetic analysis shows that pdm3 is required for odor response in one class
      of ORNs. We find that pdm3 acts in odor receptor expression in this class, and
      that the odor response can be rescued by the receptor. Another POU gene, acj6, is
      required for receptor expression in the same class, and we find a genetic
      interaction between the two POU genes. The results support a role for a POU gene
      code in receptor gene choice. pdm3 is also expressed in other ORN classes in
      which it is not required for receptor expression. For two of these classes, pdm3
      is required for normal axon targeting. Thus, this mutational analysis, the first
      for a POU class VI gene, demonstrates a role for pdm3 in both of the processes
      that define the functional organization of ORNs in the olfactory system.

PMID- 18614682
TI  - Caspase inhibitor infusion protects an avian song control circuit from seasonal
      like neurodegeneration.
AB  - Sex steroids such as androgens and estrogens have trophic effects on the brain
      and can ameliorate neurodegeneration, and the withdrawal of circulating steroids
      induces neurodegeneration in several hormone-sensitive brain areas. Very little
      is known about the underlying molecular mechanisms that mediate neuronal
      regression caused by hormone-withdrawal, however. Here we show that reduction of
      programmed cell death by local infusion of caspase inhibitors rescues a
      telencephalic nucleus in the adult avian song control system from
      neurodegeneration that is induced by hormone withdrawal. This treatment also has
      trans-synaptic effects that provide some protection of an efferent target region.
      We found that unilateral infusion of caspase inhibitors in vivo in adult white
      crowned sparrows rescued neurons within the hormone-sensitive song nucleus HVC
      (used as a proper name) from programmed cell death for as long as seven days
      after withdrawal of testosterone and a shift to short-day photoperiod and that
      the activation of caspase-3 was reduced by 59% on average in the ipsilateral HVC
      compared with the unmanipulated contralateral HVC. Caspase inhibitor infusion
      near HVC was sufficient to preserve neuron size ipsilaterally in a downstream
      nucleus, the robust nucleus of the arcopallium. This is the first report that
      sustained local application of caspase inhibitors can protect a telencephalic
      brain area from neurodegeneration in vivo and that a degenerating neural circuit
      rescued with caspase inhibitors produces sufficient trophic support to protect
      attributes of a downstream target that would otherwise degenerate. These results
      strengthen the case for the possible therapeutic use of caspase inhibitors under
      certain neurodegenerative conditions.

PMID- 18614683
TI  - Mecp2 organizes juvenile social behavior in a sex-specific manner.
AB  - Methyl-CpG-binding protein 2 (MeCP2) binds methylated DNA and recruits
      corepressor proteins to modify chromatin and alter gene transcription. Mutations
      of the MECP2 gene can cause Rett syndrome, whereas subtle reductions of MeCP2
      expression may be associated with male-dominated social and neurodevelopmental
      disorders. We report that transiently decreased amygdala Mecp2 expression during
      a sensitive period of brain sexual differentiation disrupts the organization of
      sex differences in juvenile social play behavior. Interestingly, neonatal
      treatment with Mecp2 small interfering RNA within the developing amygdala reduced
      juvenile social play behavior in males but not females. Reduced Mecp2 expression
      did not change juvenile sociability or anxiety-like behavior, suggesting that
      this disruption is associated with subtle behavioral modification. This suggests
      that Mecp2 may have an overlooked role in the organization of sexually dimorphic
      behaviors and that male juvenile behavior is particularly sensitive to Mecp2
      disruption during this period of development.

PMID- 18614684
TI  - Evidence for segregated and integrative connectivity patterns in the human Basal
      Ganglia.
AB  - Detailed knowledge of the anatomy and connectivity pattern of cortico-basal
      ganglia circuits is essential to an understanding of abnormal cortical function
      and pathophysiology associated with a wide range of neurological and
      neuropsychiatric diseases. We aim to study the spatial extent and topography of
      human basal ganglia connectivity in vivo. Additionally, we explore at an
      anatomical level the hypothesis of coexistent segregated and integrative cortico
      basal ganglia loops. We use probabilistic tractography on magnetic resonance
      diffusion weighted imaging data to segment basal ganglia and thalamus in 30
      healthy subjects based on their cortical and subcortical projections. We
      introduce a novel method to define voxel-based connectivity profiles that allow
      representation of projections from a source to more than one target region. Using
      this method, we localize specific relay nuclei within predefined functional
      circuits. We find strong correlation between tractography-based basal ganglia
      parcellation and anatomical data from previously reported invasive tracing
      studies in nonhuman primates. Additionally, we show in vivo the anatomical basis
      of segregated loops and the extent of their overlap in prefrontal, premotor, and
      motor networks. Our findings in healthy humans support the notion that
      probabilistic diffusion tractography can be used to parcellate subcortical gray
      matter structures on the basis of their connectivity patterns. The coexistence of
      clearly segregated and also overlapping connections from cortical sites to basal
      ganglia subregions is a neuroanatomical correlate of both parallel and
      integrative networks within them. We believe that this method can be used to
      examine pathophysiological concepts in a number of basal ganglia-related
      disorders.

PMID- 18614685
TI  - Sound-intensity-dependent compensation for the small interaural time difference
      cue for sound source localization.
AB  - Interaural time difference (ITD) is a major cue for sound source localization.
      However, animals with small heads experience small ITDs, making ITD detection
      difficult, particularly for low-frequency sound. Here, we describe a sound
      intensity-dependent mechanism for compensating for the small ITD cues in the
      coincidence detector neurons in the nucleus laminaris (NL) of the chicken aged
      from 3 to 29 d after hatching. The hypothesized compensation mechanisms were
      confirmed by simulation. In vivo single-unit recordings revealed an improved
      contrast of ITD tuning in low-best-frequency (<1 kHz) NL neurons by suppressing
      the firing activity at the worst ITD, whereas the firing rate was increased with
      increasing sound intensity at the best ITD. In contrast, level-dependent
      suppression was so weak in the middle- and high-best-frequency (> or =1 kHz) NL
      neurons that loud sounds led to increases in firing rate at both the best and the
      worst ITDs. The suppression of firing activity at the worst ITD in the low-best
      frequency neurons required the activation of the superior olivary nucleus (SON)
      and was eliminated by electrolytic lesions of the SON. The frequency-dependent
      suppression reflected the dense projection from the SON to the low-frequency
      region of NL. Thus, the small ITD cues available in low-frequency sounds were
      partly compensated for by a sound-intensity-dependent inhibition from the SON.

PMID- 18614686
TI  - Induction of high-frequency oscillations in a junction-coupled network.
AB  - Rhythmic oscillations of up to 600 Hz in grouped neurons frequently occur in the
      brains of animals. These high-frequency oscillations can be sustained in calcium
      free conditions and may be blocked by gap junction blockers, implying a key role
      for electrical synapses in oscillation generation. Mathematical theories have
      been developed to demonstrate oscillations mediated by electrical synapses
      without chemical modulation; however, these models have not been verified in
      animals. Here we report that oscillations of up to 686 Hz are induced by paired
      spikes of short spike intervals (SIs) in a junction-coupled network. To initiate
      oscillations, it was essential that the second spike was elicited during the
      relative refractory period. The second spike suffered from slow propagation speed
      and failure to transmit through a low-conductance junction. Thus, at the spike
      initiation site, paired spikes of short SIs triggered one transjunctional spike
      in the postsynaptic neuron. At distant synaptic sites, two transjunctional spikes
      were produced as the SI increased during spike propagation. Consequently, spike
      collision of these asymmetrical transjunctional spikes occurred in the
      interconnected network. The remaining single spike reverberated in a network
      serving as an oscillator center. Paired-spike-induced oscillations were modeled
      by computer simulation and verified electrophysiologically in a network that
      mediates the tail-flip escape response of crayfish.

PMID- 18614687
TI  - Constitutively active Akt induces enhanced myelination in the CNS.
AB  - The serine/threonine kinase Akt regulates multiple cellular functions. The
      current studies identify a new role for Akt in CNS myelination. In earlier
      studies on cultured oligodendrocytes, we showed that neuregulin signals through
      phosphatidylinositol-3'-OH kinase and Akt to enhance survival of
      oligodendrocytes. However, when transgenic animals were generated that
      overexpressed constitutively active Akt in oligodendrocytes and their progenitor
      cells, no enhanced survival of oligodendrocytes or progenitors was found. No
      alteration in the proliferation or death of progenitors was noted. In contrast,
      the major impact of Akt overexpression in oligodendrocytes was enhanced
      myelination. Most interestingly, oligodendrocytes in these mice continued
      actively myelinating throughout life. Thus, expression of constitutively active
      Akt in oligodendrocytes and their progenitor cells generated no more
      oligodendrocytes, but dramatically more myelin. The increased myelination
      continued as these mice aged, resulting in enlarged optic nerves and white matter
      areas. In older animals with enlarged white matter areas, the density of
      oligodendrocytes was reduced, but because of the increased area, the total number
      of oligodendrocytes remained comparable with wild-type controls. Interestingly,
      in these animals, overexpression of Akt in Schwann cells did not impact
      myelination. Thus, in vivo, constitutively active Akt enhances CNS myelination
      but not PNS myelination and has no impact developmentally on oligodendrocyte
      number. Understanding the unique aspects of Akt signal transduction in
      oligodendrocytes that lead to myelination rather than uncontrolled proliferation
      of oligodendrocyte progenitor cells may have important implications for
      understanding remyelination in the adult nervous system.

PMID- 18614688
TI  - Mesolimbic dopamine in desire and dread: enabling motivation to be generated by
      localized glutamate disruptions in nucleus accumbens.
AB  - An important issue in affective neuroscience concerns the role of
      mesocorticolimbic dopamine systems in positive-valenced motivation (e.g., reward)
      versus negative-valenced motivation (e.g., fear). Here, we assessed whether
      endogenous dopamine receptor stimulation in nucleus accumbens contributes to both
      appetitive behavior and fearful behavior that is generated in keyboard manner by
      local glutamate disruptions at different sites in medial shell. 6,7
      Dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) microinjections (450 ng) locally
      disrupt glutamate signals in <4 mm(3) of nucleus accumbens, and generate either
      desire or fear (or both) depending on precise rostrocaudal location in medial
      shell. At rostral shell sites, local AMPA/kainate blockade generates positive
      ingestive behavior, but the elicited motivated behavior becomes incrementally
      more fearful as the same microinjection is moved caudally. A dopamine-blocking
      mixture of D(1) and D(2) antagonists (raclopride and SCH-23390 [R(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine hydrochloride])
      was combined here in the same microinjection with DNQX to assess the role of
      endogenous local dopamine in mediating the DNQX-motivated behaviors. We report
      that local dopamine blockade prevented DNQX microinjections from generating
      appetitive behavior (eating) in rostral shell, and equally prevented DNQX from
      generating fearful behavior (defensive treading) in caudal shell. We conclude
      that local dopamine is needed to enable disruptions of corticolimbic glutamate
      signals in shell to generate either positive incentive salience or negative
      fearful salience (valence depending on site and other conditions). Thus, dopamine
      interacts with localization of valence-biased glutamate circuits in medial shell
      to facilitate keyboard stimulation of both appetitive and fearful motivations.

PMID- 18614689
TI  - Sleep deprivation effects on circadian clock gene expression in the cerebral
      cortex parallel electroencephalographic differences among mouse strains.
AB  - Sleep deprivation (SD) results in increased electroencephalographic (EEG) delta
      power during subsequent non-rapid eye movement sleep (NREMS) and is associated
      with changes in the expression of circadian clock-related genes in the cerebral
      cortex. The increase of NREMS delta power as a function of previous wake duration
      varies among inbred mouse strains. We sought to determine whether SD-dependent
      changes in circadian clock gene expression parallel this strain difference
      described previously at the EEG level. The effects of enforced wakefulness of
      incremental durations of up to 6 h on the expression of circadian clock genes
      (bmal1, clock, cry1, cry2, csnk1epsilon, npas2, per1, and per2) were assessed in
      AKR/J, C57BL/6J, and DBA/2J mice, three strains that exhibit distinct EEG
      responses to SD. Cortical expression of clock genes subsequent to SD was
      proportional to the increase in delta power that occurs in inbred strains: the
      strain that exhibits the most robust EEG response to SD (AKR/J) exhibited
      dramatic increases in expression of bmal1, clock, cry2, csnkIepsilon, and npas2,
      whereas the strain with the least robust response to SD (DBA/2) exhibited either
      no change or a decrease in expression of these genes and cry1. The effect of SD
      on circadian clock gene expression was maintained in mice in which both of the
      cryptochrome genes were genetically inactivated. cry1 and cry2 appear to be
      redundant in sleep regulation as elimination of either of these genes did not
      result in a significant deficit in sleep homeostasis. These data demonstrate
      transcriptional regulatory correlates to previously described strain differences
      at the EEG level and raise the possibility that genetic differences underlying
      circadian clock gene expression may drive the EEG differences among these
      strains.

PMID- 18614690
TI  - The role of hypothalamic mammalian target of rapamycin complex 1 signaling in
      diet-induced obesity.
AB  - The mammalian target of rapamycin (mTOR) kinase is a key regulator of several
      cellular functions, including cell growth and differentiation. Because
      hypothalamic mTOR complex 1 (mTORC1) signaling has been implicated as a target of
      leptin in the regulation of energy balance, we investigated its role in obesity
      induced leptin resistance. In contrast to rats maintained on a low-fat (LF) diet
      for 3 weeks, rats maintained on a high-fat (HF)-diet had no anorexic response to
      intracerebroventricular leptin. Western blot analysis revealed that leptin was
      unable to modulate hypothalamic mTORC1 signaling in the HF group, whereas it
      significantly induced phosphorylation of both S6 kinase 1 (S6K1) and S6 ribosomal
      protein (S6) in the LF group. Similar to leptin, the cytokine ciliary
      neurotrophic factor (CNTF) induces hypophagia and increases signal transduction
      activator of transcription 3 phosphorylation. However, CNTF and its analog
      CNTF(Ax15) activate leptin-like pathways in the hypothalamus, even in leptin
      resistant states, including diet-induced obesity. Intracerebroventricular
      CNTF(Ax15) decreased 24 h food intake and body weight in rats on HF or LF diets
      and increased the phosphorylation of hypothalamic S6K1 and S6 in a comparable way
      in both diets. Importantly, mice lacking the expression of S6K1 (S6K1(-/-)) did
      not respond to the anorectic action of either leptin or CNTF(Ax15), implying a
      crucial role for S6K1 in modulating the actions of these two cytokines. Finally,
      exposure to HF diet decreased mTORC1 signaling within the hypothalamus. Overall,
      these findings point strongly to the possibility that reduced hypothalamic mTORC1
      signaling contributes to the development of hyperphagia, weight gain, and leptin
      resistance during diet-induced obesity.

PMID- 18614691
TI  - Role for subthalamic nucleus neurons in switching from automatic to controlled
      eye movement.
AB  - The subthalamic nucleus (STN) of the basal ganglia is an important element of
      motor control. This is demonstrated by involuntary movements induced by STN
      lesions and the successful treatment of Parkinson's disease by STN stimulation.
      However, it is still unclear how individual STN neurons participate in motor
      control. Here, we report that the STN has a function in switching from automatic
      to volitionally controlled eye movement. In the STN of trained macaque monkeys,
      we found neurons that showed a phasic change in activity specifically before
      volitionally controlled saccades which were switched from automatic saccades. A
      majority of switch-related neurons were considered to inhibit no-longer-valid
      automatic processes, and the inhibition started early enough to enable the animal
      to switch. We suggest that the STN mediates the control signal originated from
      the medial frontal cortex and implements the behavioral switching function using
      its connections with other basal ganglia nuclei and the superior colliculus.

PMID- 18614694
TI  - Effect of a classroom-based behavioral intervention package on the improvement of
      children's sitting posture in Japan.
AB  - The present study evaluates the effect of a classroom-based behavioral
      intervention package to improve Japanese elementary school children's sitting
      posture in regular classrooms (N=68). This study uses a multiple-baseline design
      across two classrooms with a modified repeated reversal within each class. The
      article defines appropriate sitting posture as behavior composed of four
      components (feet, buttocks, back, and a whole body). The intervention package
      includes modeling, correspondence training, prompt, and reinforcement, among
      others. The authors counted the number of children with appropriate sitting
      posture in each classroom across all 28 sessions throughout the study.
      Interobserver agreement of appropriate sitting posture ranged from 80% to 100%.
      As a result of the intervention, the mean proportion of children with appropriate
      posture increased from approximately 20% to 90%. In addition, their academic
      writing productivity increased with the improved sitting posture. Teachers'
      acceptance of the intervention program proved to be excellent.

PMID- 18614693
TI  - STAT3 is a critical regulator of astrogliosis and scar formation after spinal
      cord injury.
AB  - Signaling mechanisms that regulate astrocyte reactivity and scar formation after
      spinal cord injury (SCI) are not well defined. We used the Cre recombinase (Cre)
      loxP system under regulation of the mouse glial fibrillary acidic protein (GFAP)
      promoter to conditionally delete the cytokine and growth factor signal
      transducer, signal transducer and activator of transcription 3 (STAT3), from
      astrocytes. After SCI in GFAP-Cre reporter mice, >99% of spinal cord cells that
      exhibited Cre activity as detected by reporter protein expression were GFAP
      expressing astrocytes. Conditional deletion (or knock-out) of STAT3 (STAT3-CKO)
      from astrocytes in GFAP-Cre-loxP mice was confirmed in vivo and in vitro. In
      uninjured adult STAT3-CKO mice, astrocytes appeared morphologically similar to
      those in STAT3+/+ mice except for a partially reduced expression of GFAP. In
      STAT3+/+ mice, phosphorylated STAT3 (pSTAT3) was not detectable in astrocytes in
      uninjured spinal cord, and pSTAT3 was markedly upregulated after SCI in
      astrocytes and other cell types near the injury. Mice with STAT3-CKO from
      astrocytes exhibited attenuated upregulation of GFAP, failure of astrocyte
      hypertrophy, and pronounced disruption of astroglial scar formation after SCI.
      These changes were associated with increased spread of inflammation, increased
      lesion volume and partially attenuated motor recovery over the first 28 d after
      SCI. These findings indicate that STAT3 signaling is a critical regulator of
      certain aspects of reactive astrogliosis and provide additional evidence that
      scar-forming astrocytes restrict the spread of inflammatory cells after SCI.

PMID- 18614695
TI  - Effects of an informational brochure, lottery-based financial incentive, and
      public posting on absenteeism of direct-care human services employees.
AB  - Chronic absenteeism is a problem encountered by many human services
      organizations. Large-scale intervention projects to reduce staff absences have
      incorporated applied behavior analysis methods but there are few studies in the
      extant literature. In the present study, the authors record staff absenteeism at
      a specialized school for students with developmental disabilities during a
      baseline phase and following implementation of a systems-change intervention that
      included distribution of an informational brochure, lottery-based financial
      incentive, and public posting. Intervention is found to be associated with
      improved staff attendance and reduced "lost wages." Practice and research
      implications are discussed.

PMID- 18614692
TI  - Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking
      uracil DNA glycosylase.
AB  - Folate deficiency and resultant increased homocysteine levels have been linked
      experimentally and epidemiologically with neurodegenerative conditions like
      stroke and dementia. Moreover, folate deficiency has been implicated in the
      pathogenesis of psychiatric disorders, most notably depression. We hypothesized
      that the pathogenic mechanisms include uracil misincorporation and, therefore,
      analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase
      (Ung-/-) versus wild-type controls. Folate depletion increased nuclear mutation
      rates in Ung-/- embryonic fibroblasts, and conferred death of cultured Ung-/-
      hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months
      induced degeneration of CA3 pyramidal neurons in Ung-/- but not Ung+/+ mice along
      with decreased hippocampal expression of brain-derived neurotrophic factor
      protein and decreased brain levels of antioxidant glutathione. Furthermore, FD
      induced cognitive deficits and mood alterations such as anxious and despair-like
      behaviors that were aggravated in Ung-/- mice. Independent of Ung genotype, FD
      increased plasma homocysteine levels, altered brain monoamine metabolism, and
      inhibited adult hippocampal neurogenesis. These results indicate that impaired
      uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction
      induced by experimental folate deficiency.

PMID- 18614696
TI  - Understanding clinical anger and violence: the anger avoidance model.
AB  - Although anger is a primary emotion and holds clear functional necessities, the
      presence of anger and its behavioral manifestations of aggression/violence can
      have serious emotional, health, and social consequences. Despite such
      consequences, the construct of clinical anger has to date suffered from few
      theoretical and treatment advancements and has received insufficient research
      attention. Thus, the purpose of this article is to introduce the Anger Avoidance
      Model, which is a new conceptualization of clinical anger and its behavioral
      manifestations. The Anger Avoidance Model suggests that among anger patients, a
      chronic early aversive history leads to information processing biases and emotion
      regulation deficits, which in turn result in intense efforts to avoid the
      experience of anger. This avoidance takes the form of hostile rumination
      (cognitive avoidance) and aggressive and violent behavior (behavioral avoidance).
      This model holds clear implications for research and treatment of this
      challenging clinical phenomenon.

PMID- 18614697
TI  - Testing the construct validity of Dixon and Johnson's (2007) Gambling Functional
      Assessment.
AB  - The Gambling Functional Assessment (GFA; Dixon & Johnson, 2007) is a 20-item self
      report inventory identifying four potential consequences maintaining gambling
      behavior. Exploratory and confirmatory factor analyses are performed for two
      large, nonclinical samples of university undergraduates. For the exploratory
      analysis, the optimal model yields two factors: Positive Reinforcement
      (correlated with GFA Sensory, Attention, and Tangible scores) and Negative
      Reinforcement (correlated with GFA Escape scores). One GFA item fails to load on
      either factor adequately. Factor loadings are confirmed using structural equation
      modeling for the second sample. The resulting model yields a mix of adequate and
      suboptimal fit indicators. Although the 2-factor model of the GFA has great
      theoretical utility and shows significant promise, confirmation within clinical
      samples of gamblers will be necessary to further validate the model. GFA Escape
      scores are uniquely distributed in the two samples and may represent functions
      most likely to maintain pathological gambling.

PMID- 18614698
TI  - Posttraumatic stress disorder and social support in female victims of sexual
      assault: the impact of spousal involvement on the efficacy of cognitive
      behavioral therapy.
AB  - The goal of this study is to enhance the efficacy of CBT with victims of sexual
      assault suffering from PTSD by getting the spouse involved. Thus, in addition to
      attempting to reduce PTSD symptoms, the therapy focuses on improving the support
      offered by the spouse and favors management of the impact of the traumatic event
      within the couple. A single-case, multiple-baseline across-subjects design is
      used. Three victims of sexual assault with a diagnosis of PTSD participated in
      the study. Results at posttreatment and at 3-month follow-up are promising. None
      of the participants presents a diagnosis of PTSD, and all report a significant
      improvement in their satisfaction with the support received from their spouses.

PMID- 18614699
TI  - The emergence and loss of gonadotropin-releasing hormone in protostomes:
      orthology, phylogeny, structure, and function.
AB  - Gonadotropin-releasing hormone (GNRH) is a neuropeptide critical for reproductive
      activation and maintenance in vertebrates. The recent elucidation of molluscan
      GNRH-like sequences led to several important questions regarding the evolution of
      the GNRH family. For instance, are molluscan and chordate GNRHs true orthologs?
      Has GNRH been retained in most protostomian lineages? What was the function of
      the ancestral GNRH? The goal of this review is to provide a critical analysis of
      GNRH evolution based on data available from the known forms of protostomian GNRH.
      Judging from the orthology between chordate and protostomian GNRH receptors,
      conservation of several structural motifs on the GNRH peptide, and exon/intron
      arrangement conserved between protostomian and chordate GNRH genomic sequences,
      we conclude that chordate and protostomian GNRHs likely share a common ancestor.
      Based on our analysis of phylogenetic distribution, we also hypothesize that GNRH
      may have been lost in the ecdysozoan lineage but preserved in lophotrochozoans.
      Lastly, we propose that the ancestral function of GNRH is to serve as a general
      neural regulator, and its considerable specialization in reproduction seen in
      chordates is a consequence of neofunctionalization following gene duplication.

PMID- 18614701
TI  - Stage-specific gene expression during fish spermatogenesis as determined by laser
      capture microdissection and quantitative-PCR in sea bass (Dicentrarchus labrax)
      gonads.
AB  - The role of genes implicated in the regulation of spermatogenesis and their
      patterns of expression is still poorly understood. In this study, we took
      advantage of the cystic arrangement of the teleost testis to set up a laser
      capture microdissection procedure to isolate cells from cysts containing
      spermatogonia, spermatocytes, spermatids, or spermatozoa. We then used
      quantitative PCR to determine the stage-specific expression patterns of the germ
      cell marker vasa; gonadal aromatase (cyp19a); estrogen receptors (ers) alpha,
      beta1, and beta2 (era, erb1, and erb2, respectively); 11beta-hydroxylase
      (cyp11b1); androgen receptor beta (arb); insulinlike growth factor 1 (igf1); and
      sox17. vasa had the highest mRNA levels, followed by genes involved in androgen
      metabolism (cyp11b1 and arb). Most genes associated with estrogen metabolism
      (cyp19a, era, and erb1) had a lower expression, whereas igf1 and sox17 exhibited
      the lowest mRNA levels. Comparison of changes in mRNA levels revealed five
      patterns of gene expression, in general with progressively lower expression seen
      as spermatogenesis advanced. igf1 and sox17 were exclusively expressed in
      spermatogonia-containing cysts, suggesting effects during the proliferative
      stage. Genes involved in androgen synthesis (cyp11b1) and action (arb) peaked
      during the early stages of spermatogenesis and then sharply decreased. In
      contrast, genes associated with estrogen action, particularly erb2 and era,
      showed a more gradual decrease. Together, these results demonstrate the
      usefulness of fish models and suggest that whereas androgens are required at high
      levels and may exert their major actions at the initial stages of
      spermatogenesis, estrogens are also essential, albeit required at lower levels,
      and with a more generalized influence.

PMID- 18614700
TI  - Expression of type-1 cannabinoid receptor during rat postnatal testicular
      development: possible involvement in adult leydig cell differentiation.
AB  - Endocannabinoids are lipidic modulators able to bind cannabinoid receptors
      (CNRs). Two types of CNRs have been cloned, CNR1 (central) and CNR2 (peripheral).
      The objectives of the present study were to investigate the expression pattern of
      CNR1 in the rat testis during prepubertal development and to define the CNR1
      spatiotemporal pattern. From 31 to 60 days of age, CNR1 was immunolocalized in
      round elongating spermatids and spermatozoa, suggesting an important role for
      this receptor in spermatogenesis. From 14 to 60 days of age, adult Leydig cells
      (ALCs) at different developmental stages were positive for CNR1. In particular,
      CNR1 expression in differentiating ALCs was negatively correlated to cell
      division. Bromodeoxyuridine uptake experiments on serial sections showed that
      immature Leydig cells in mitosis were negative for CNR1; in contrast, immature
      nonmitotic Leydig cells were positive for CNR1. A further observation of few ALCs
      in CNR1KO mice validates the role of CNR1 during proliferative activity involved
      in ALC differentiation. In addition, starting from 41 days of age, a faint CNR1
      signal was also observed in Sertoli cells. Taken together, these results
      demonstrate the first clear evidence (to our knowledge) of CNR1 in mammalian
      germinal epithelium, ALCs, and Sertoli cells and indicate that differentiation of
      ALCs may depend on the endocannabinoid system.

PMID- 18614703
TI  - Vertebrate extracellular preovulatory and postovulatory egg coats.
AB  - Extracellular egg coats deposited by maternal or embryonic tissues surround all
      vertebrate conceptuses during early development. In oviparous species, the time
      of hatching from extracellular coats can be considered equivalent to the time of
      birth in viviparous species. Extracellular coats must be lost during gestation
      for implantation and placentation to occur in some viviparous species. In the
      most recent classification of vertebrate extracellular coats, Boyd and Hamilton
      (Cleavage, early development and implantation of the egg. In: Parkes AS (ed.),
      Marshall's Physiology of Reproduction, vol. 2, 3rd ed. London: Longmans, Green &
      Co; 1961:1-126) defined the coat synthesized by the oocyte during oogenesis as
      primary and the coat deposited by follicle cells surrounding the oocyte as
      secondary. Tertiary egg coats are those synthesized and deposited around the
      primary or secondary coat by the maternal reproductive tract. This classification
      is difficult to reconcile with recent data collected using modern molecular
      biological techniques that can accurately establish the site of coat precursor
      synthesis and secretion. We propose that a modification to the classification by
      Boyd and Hamilton is required. Vertebrate egg coats should be classed as
      belonging to the following two broad groups: the preovulatory coat, which is
      deposited during oogenesis by the oocyte or follicle cells, and the postovulatory
      coats, which are deposited after fertilization by the reproductive tract or
      conceptus. This review discusses the origin and classification of vertebrate
      extracellular preovulatory and postovulatory coats and illustrates what is known
      about coat homology between the vertebrate groups.

PMID- 18614702
TI  - Role of caspase 2 in apoptotic signaling in primate and murine germ cells.
AB  - This study investigates the role of caspase 2 in apoptotic signaling of nonhuman
      primate male germ cells triggered by mild testicular hyperthermia, testosterone
      (T(e)) implants, or by combined interventions. Mean incidence of germ cell
      apoptosis increased significantly by Day 3 in the heat (H(e)) alone group and by
      Day 8 in the Te alone group but peaked at Day 3 in H(e) + T(e) group. We found
      activation of caspase 2 in both germ cells and Sertoli cells after induction of
      apoptosis. Most notably, active caspase 2 immunoreactivity was detected only in
      those germ cells susceptible to apoptosis compared with controls, where little or
      no such staining is detected. To further explore the role of caspase 2 in
      regulating male germ cell death, we next evaluated the efficacy of caspase 2
      inhibition in preventing or attenuating heat-induced germ cell apoptosis in rats.
      Caspase 2 inhibition significantly (P < 0.05) prevented such heat-induced germ
      cell apoptosis. The protection offered by the caspase 2 inhibitor occurred
      upstream of mitochondria, involving suppression of mitogen-activated protein
      kinase (MAPK) 14 activation and inducible nitric oxide synthase (NOS2) induction
      and, in turn, suppression of cytochrome c-mediated death pathway. Together, our
      results show that caspase 2 is activated in male germ cells undergoing apoptosis
      in nonhuman primates after heat stress, hormonal deprivation, or after combined
      interventions. Blockade of caspase 2 activation prevents heat-induced germ cell
      apoptosis in rats by suppressing the MAPK14- and NO-mediated intrinsic pathway
      signaling.

PMID- 18614704
TI  - Mammary gland development in transforming growth factor beta1 null mutant mice:
      systemic and epithelial effects.
AB  - The cytokine-transforming growth factor beta1 (TGFB1) is implicated in
      development of the mammary gland through regulation of epithelial cell
      proliferation and differentiation during puberty and pregnancy. We compared
      mammary gland morphogenesis in virgin Tgfb1(+/+), Tgfb1(+/-), and Tgfb1(-/-) mice
      and transplanted Tgfb1(+/+) and Tgfb1(-/-) epithelium to determine the impact of
      TGFB1 deficiency on development. When mammary gland tissue was evaluated relative
      to the timing of puberty, invasion through the mammary fat pad of the ductal
      epithelium progressed similarly, irrespective of genotype, albeit fewer terminal
      end buds were observed in mammary glands from Tgfb1(-/-) mice. The terminal end
      buds appeared to be normal morphologically, and a comparable amount of epithelial
      proliferation was evident. When transplanted into wild-type recipients, however,
      Tgfb1(-/-) epithelium showed accelerated invasion compared with Tgfb1(+/+)
      epithelium. This suggests that the normal rate of ductal extension in Tgfb1(-/-)
      null mutant mice is the net result of impaired endocrine or paracrine support
      acting to limit the consequences of unrestrained epithelial growth. By adulthood,
      mammary glands in cycling virgin Tgfb1(-/-) mice were morphologically similar to
      those in Tgfb1(+/+) and Tgfb1(+/-) animals, with a normal branching pattern, and
      the tissue differentiated into early alveolar structures in the diestrous phase
      of the ovarian cycle. Transplanted mammary gland epithelium showed a similar
      extent of ductal branching and evidence of secretory differentiation of luminal
      cells in pregnancy. These results reveal two opposing actions of TGFB1 during
      pubertal mammary gland morphogenesis: autocrine inhibition of epithelial ductal
      growth, and endocrine or paracrine stimulation of epithelial ductal growth.

PMID- 18614705
TI  - Enhanced tolerance to oxidative stress in transgenic Arabidopsis plants
      expressing proteins of unknown function.
AB  - Over one-quarter of all plant genes encode proteins of unknown function that can
      be further classified as proteins with obscure features (POFs), which lack
      currently defined motifs or domains, or proteins with defined features, which
      contain at least one previously defined domain or motif. Although empirical data
      in the form of transcriptome and proteome profiling suggest that many of these
      proteins play important roles in plants, their functional characterization
      remains one of the main challenges in modern biology. To begin the functional
      annotation of proteins with unknown function, which are involved in the oxidative
      stress response of Arabidopsis (Arabidopsis thaliana), we generated transgenic
      Arabidopsis plants that constitutively expressed 23 different POFs (four of which
      were specific to Arabidopsis) and 18 different proteins with defined features.
      All were previously found to be expressed in response to oxidative stress in
      Arabidopsis. Transgenic plants were tested for their tolerance to oxidative
      stress imposed by paraquat or t-butyl hydroperoxide, or were subjected to
      osmotic, salinity, cold, and heat stresses. More than 70% of all expressed
      proteins conferred tolerance to oxidative stress. In contrast, >90% of the
      expressed proteins did not confer enhanced tolerance to the other abiotic
      stresses tested, and approximately 50% rendered plants more susceptible to
      osmotic or salinity stress. Two Arabidopsis-specific POFs, and an Arabidopsis and
      Brassica-specific protein of unknown function, conferred enhanced tolerance to
      oxidative stress. Our findings suggest that tolerance to oxidative stress
      involves mechanisms and pathways that are unknown at present, including some that
      are specific to Arabidopsis or the Brassicaceae.

PMID- 18614706
TI  - Sensitive to freezing6 integrates cellular and environmental inputs to the plant
      circadian clock.
AB  - The sensitive to freezing6 (sfr6) mutant of Arabidopsis (Arabidopsis thaliana) is
      late flowering in long days due to reduced expression of components in the
      photoperiodic flowering pathway in long-day photoperiods. Microarray analysis of
      gene expression showed that a circadian clock-associated motif, the evening
      element, was overrepresented in promoters of genes down-regulated in sfr6 plants.
      Analysis of leaf movement rhythms found sfr6 plants showed a sucrose (Suc)
      dependent long period phenotype; unlike wild-type Arabidopsis, the clock in sfr6
      plants did not have a shorter rhythm in the presence of Suc. Other developmental
      responses to Suc were unaltered in sfr6 plants, suggesting insensitivity to Suc
      is restricted to the clock. We investigated the effect of sfr6 and Suc upon clock
      gene expression over 24 h. The sfr6 mutation resulted in reduced expression of
      the clock components CIRCADIAN CLOCK ASSOCIATED1, GIGANTEA, and TIMING OF CAB1.
      These changes occurred independently of Suc supplementation. Wild-type plants
      showed small increases in clock gene expression in the presence of Suc; this
      response to Suc was reduced in sfr6 plants. This study shows that large changes
      in level and timing of clock gene expression may have little effect upon clock
      outputs. Moreover, although Suc influences the period and accuracy of the
      Arabidopsis clock, it results in relatively minor changes in clock gene
      expression.

PMID- 18614707
TI  - A novel type of thioredoxin dedicated to symbiosis in legumes.
AB  - Thioredoxins (Trxs) constitute a family of small proteins in plants. This family
      has been extensively characterized in Arabidopsis (Arabidopsis thaliana), which
      contains six different Trx types: f, m, x, and y in chloroplasts, o in
      mitochondria, and h mainly in cytosol. A detailed study of this family in the
      model legume Medicago truncatula, realized here, has established the existence of
      two isoforms that do not belong to any of the types previously described. As no
      possible orthologs were further found in either rice (Oryza sativa) or poplar
      (Populus spp.), these novel isoforms may be specific for legumes. Nevertheless,
      on the basis of protein sequence and gene structure, they are both related to
      Trxs m and probably have evolved from Trxs m after the divergence of the higher
      plant families. They have redox potential values similar to those of the
      classical Trxs, and one of them can act as a substrate for the M. truncatula NADP
      Trx reductase A. However, they differ from classical Trxs in that they possess an
      atypical putative catalytic site and lack disulfide reductase activity with
      insulin. Another important feature is the presence in both proteins of an N
      terminal extension containing a putative signal peptide that targets them to the
      endoplasmic reticulum, as demonstrated by their transient expression in fusion
      with the green fluorescent protein in M. truncatula or Nicotiana benthamiana
      leaves. According to their pattern of expression, these novel isoforms function
      specifically in symbiotic interactions in legumes. They were therefore given the
      name of Trxs s, s for symbiosis.

PMID- 18614708
TI  - Two Arabidopsis ADP-glucose pyrophosphorylase large subunits (APL1 and APL2) are
      catalytic.
AB  - ADP-glucose (Glc) pyrophosphorylase (ADP-Glc PPase) catalyzes the first committed
      step in starch biosynthesis. Higher plant ADP-Glc PPase is a heterotetramer
      (alpha(2)beta(2)) consisting of two small and two large subunits. There is
      increasing evidence that suggests that catalytic and regulatory properties of the
      enzyme from higher plants result from the synergy of both types of subunits. In
      Arabidopsis (Arabidopsis thaliana), two genes encode small subunits (APS1 and
      APS2) and four large subunits (APL1-APL4). Here, we show that in Arabidopsis,
      APL1 and APL2, besides their regulatory role, have catalytic activity.
      Heterotetramers formed by combinations of a noncatalytic APS1 and the four large
      subunits showed that APL1 and APL2 exhibited ADP-Glc PPase activity with
      distinctive sensitivities to the allosteric activator (3-phosphoglycerate).
      Mutation of the Glc-1-P binding site of Arabidopsis and potato (Solanum
      tuberosum) isoforms confirmed these observations. To determine the relevance of
      these activities in planta, a T-DNA mutant of APS1 (aps1) was characterized. aps1
      is starchless, lacks ADP-Glc PPase activity, APS1 mRNA, and APS1 protein, and is
      late flowering in long days. Transgenic lines of the aps1 mutant, expressing an
      inactivated form of APS1, recovered the wild-type phenotype, indicating that APL1
      and APL2 have catalytic activity and may contribute to ADP-Glc synthesis in
      planta.

PMID- 18614709
TI  - Mobilization of rubisco and stroma-localized fluorescent proteins of chloroplasts
      to the vacuole by an ATG gene-dependent autophagic process.
AB  - During senescence and at times of stress, plants can mobilize needed nitrogen
      from chloroplasts in leaves to other organs. Much of the total leaf nitrogen is
      allocated to the most abundant plant protein, Rubisco. While bulk degradation of
      the cytosol and organelles in plants occurs by autophagy, the role of autophagy
      in the degradation of chloroplast proteins is still unclear. We have visualized
      the fate of Rubisco, stroma-targeted green fluorescent protein (GFP) and DsRed,
      and GFP-labeled Rubisco in order to investigate the involvement of autophagy in
      the mobilization of stromal proteins to the vacuole. Using immunoelectron
      microscopy, we previously demonstrated that Rubisco is released from the
      chloroplast into Rubisco-containing bodies (RCBs) in naturally senescent leaves.
      When leaves of transgenic Arabidopsis (Arabidopsis thaliana) plants expressing
      stroma-targeted fluorescent proteins were incubated with concanamycin A to
      inhibit vacuolar H(+)-ATPase activity, spherical bodies exhibiting GFP or DsRed
      fluorescence without chlorophyll fluorescence were observed in the vacuolar
      lumen. Double-labeled immunoelectron microscopy with anti-Rubisco and anti-GFP
      antibodies confirmed that the fluorescent bodies correspond to RCBs. RCBs could
      also be visualized using GFP-labeled Rubisco directly. RCBs were not observed in
      leaves of a T-DNA insertion mutant in ATG5, one of the essential genes for
      autophagy. Stroma-targeted DsRed and GFP-ATG8 fusion proteins were observed
      together in autophagic bodies in the vacuole. We conclude that Rubisco and stroma
      targeted fluorescent proteins can be mobilized to the vacuole through an ATG gene
      dependent autophagic process without prior chloroplast destruction.

PMID- 18614710
TI  - The binding of auxin to the Arabidopsis auxin influx transporter AUX1.
AB  - The cellular import of the hormone auxin is a fundamental requirement for the
      generation of auxin gradients that control a multitude of plant developmental
      processes. The AUX/LAX family of auxin importers, exemplified by AUX1 from
      Arabidopsis (Arabidopsis thaliana), has been shown to mediate auxin import when
      expressed heterologously. The quantitative nature of the interaction between AUX1
      and its transport substrate indole-3-acetic acid (IAA) is incompletely
      understood, and we sought to address this in the present investigation. We
      expressed AUX1 to high levels in a baculovirus expression system and prepared
      membrane fragments from baculovirus-infected insect cells. These membranes proved
      suitable for determination of the binding of IAA to AUX1 and enabled us to
      determine a K(d) of 2.6 mum, comparable with estimates for the K(m) for IAA
      transport. The efficacy of a number of auxin analogues and auxin transport
      inhibitors to displace IAA binding from AUX1 has also been determined and can be
      rationalized in terms of their physiological effects. Determination of the
      parameters describing the initial interaction between a plant transporter and its
      hormone ligand provides novel quantitative data for modeling auxin fluxes.

PMID- 18614711
TI  - Functional characterization of an unusual phytochelatin synthase, LjPCS3, of
      Lotus japonicus.
AB  - In plants and many other organisms, phytochelatin synthase (PCS) catalyzes the
      synthesis of phytochelatins from glutathione in the presence of certain metals
      and metalloids. We have used budding yeast (Saccharomyces cerevisiae) as a
      heterologous system to characterize two PCS proteins, LjPCS1 and LjPCS3, of the
      model legume Lotus japonicus. Initial experiments revealed that the metal
      tolerance of yeast cells in vivo depends on the concentrations of divalent
      cations in the growth medium. Detailed in vivo (intact cells) and in vitro
      (broken cells) assays of PCS activity were performed with yeast expressing the
      plant enzymes, and values of phytochelatin production for each metal tested were
      normalized with respect to those of cadmium to correct for the lower expression
      level of LjPCS3. Our results showed that lead was the best activator of LjPCS1 in
      the in vitro assay, whereas, for both assays, arsenic, iron, and aluminum were
      better activators of LjPCS3 and mercury was similarly active with the two
      enzymes. Most interestingly, zinc was a powerful activator, especially of LjPCS3,
      when assayed in vivo, whereas copper and silver were the strongest activators in
      the in vitro assay. We conclude that the in vivo and in vitro assays are useful
      and complementary to assess the response of LjPCS1 and LjPCS3 to a wide range of
      metals and that the differences in the C-terminal domains of the two proteins are
      responsible for their distinct expression levels or stabilities in heterologous
      systems and patterns of metal activation.

PMID- 18614712
TI  - GR24, a synthetic analog of strigolactones, stimulates the mitosis and growth of
      the arbuscular mycorrhizal fungus Gigaspora rosea by boosting its energy
      metabolism.
AB  - Arbuscular mycorrhizal (AM) fungi are obligate biotrophs that participate in a
      highly beneficial root symbiosis with 80% of land plants. Strigolactones are
      trace molecules in plant root exudates that are perceived by AM fungi at
      subnanomolar concentrations. Within just a few hours, they were shown to
      stimulate fungal mitochondria, spore germination, and branching of germinating
      hyphae. In this study we show that treatment of Gigaspora rosea with a
      strigolactone analog (GR24) causes a rapid increase in the NADH concentration,
      the NADH dehydrogenase activity, and the ATP content of the fungal cell. This
      fully and rapidly (within minutes) activated oxidative metabolism does not
      require new gene expression. Up-regulation of the genes involved in mitochondrial
      metabolism and hyphal growth, and stimulation of the fungal mitotic activity,
      take place several days after this initial boost to the cellular energy of the
      fungus. Such a rapid and powerful action of GR24 on G. rosea cells suggests that
      strigolactones are important plant signals involved in switching AM fungi toward
      full germination and a presymbiotic state.

PMID- 18614713
TI  - Immunolocalization of solanaceous SUT1 proteins in companion cells and xylem
      parenchyma: new perspectives for phloem loading and transport.
AB  - Leaf sucrose (Suc) transporters are essential for phloem loading and long
      distance partitioning of assimilates in plants that load their phloem from the
      apoplast. Suc loading into the phloem is indispensable for the generation of the
      osmotic potential difference that drives phloem bulk flow and is central for the
      long-distance movement of phloem sap compounds, including hormones and signaling
      molecules. In previous analyses, solanaceous SUT1 Suc transporters from tobacco
      (Nicotiana tabacum), potato (Solanum tuberosum), and tomato (Solanum
      lycopersicum) were immunolocalized in plasma membranes of enucleate sieve
      elements. Here, we present data that identify solanaceous SUT1 proteins with high
      specificity in phloem companion cells. Moreover, comparisons of SUT1 localization
      in the abaxial and adaxial phloem revealed higher levels of SUT1 protein in the
      abaxial phloem of all three solanaceous species, suggesting different
      physiological roles for these two types of phloem. Finally, SUT1 proteins were
      identified in files of xylem parenchyma cells, mainly in the bicollateral veins.
      Together, our data provide new insight into the role of SUT1 proteins in
      solanaceous species.

PMID- 18614714
TI  - Manganese efficiency in barley: identification and characterization of the metal
      ion transporter HvIRT1.
AB  - Manganese (Mn) deficiency is an important plant nutritional disorder in many
      parts of the world. Barley (Hordeum vulgare) genotypes differ considerably in
      their ability to grow in soils with low Mn(2+) availability. Differential
      genotypic Mn efficiency can be attributed to differences in Mn(2+) uptake
      kinetics in the low nanomolar concentration range. However, the molecular basis
      for these differences has not yet been clarified. We present here the
      identification and characterization of the first barley gene encoding a plasma
      membrane-localized metal transport protein able to transport Mn(2+). The gene is
      designated HvIRT1 (for IRON-REGULATED TRANSPORTER1) because it belongs to the ZIP
      gene family and has a high similarity to rice (Oryza sativa) OsIRT1. A novel
      yeast uptake assay based on inductively coupled plasma-mass spectrometry analysis
      of 31 different metal and metalloid ions showed that the HvIRT1 protein, in
      addition to Mn(2+), also transported Fe(2+)/Fe(3+), Zn(2+), and Cd(2+). Both Mn
      and iron deficiency induced an up-regulation of HvIRT1 in two barley genotypes
      differing in Mn efficiency, but the expression levels in all cases were highest
      (up to 40%) in the Mn-efficient genotype. The higher expression of HvIRT1
      correlated with an increased Mn(2+) uptake rate. We conclude that HvIRT1 is an
      important component controlling Mn(2+) uptake in barley roots and contributes to
      genotypic differences in Mn(2+) uptake kinetics.

PMID- 18614715
TI  - Serum leptin concentrations and markers of immune function in overweight or obese
      postmenopausal women.
AB  - Experimental studies and case reports suggest a multifunctional role of leptin in
      immune function. However, clinical studies of leptin in healthy individuals with
      a comprehensive assessment of immunity are lacking. This study investigated
      associations between serum leptin concentrations and multiple biomarkers of
      cellular immunity and inflammation among 114 healthy postmenopausal, overweight,
      or obese women. Leptin was measured by RIA. C-reactive protein (CRP) and serum
      amyloid A (SAA) were measured by nephelometry. Flow cytometry was used to measure
      natural killer (NK) cell cytotoxicity and to enumerate and phenotype lymphocyte
      subsets. T-lymphocyte proliferation was assessed in response to
      phytohemagluttinin, as well as to anti-CD3 antibodies by the flow cytometric cell
      division tracking method. Multiple linear regression analysis with adjustment for
      confounding factors and log transformation, where appropriate, was used. Serum
      leptin concentrations were positively associated with serum CRP, SAA, and
      interleukin 6 (IL6) (P<0.0001, P=0.01, and P=0.04 respectively), more strongly
      among women with a body mass index (BMI) <30 kg/m(2). The associations were
      attenuated after adjustment for measured body composition, yet remained
      significant for CRP and SAA. No statistically significant associations were
      observed between leptin and NK cytotoxicity, lymphocyte subpopulations, or T
      lymphocyte proliferation. This study fills an important gap in knowledge about
      the relationship between leptin concentrations and immune function in healthy
      individuals. Findings support an association between serum leptin and the
      inflammatory proteins CRP and SAA, which appears to be mediated only partly by
      adipose tissue. Our study does not support a link between leptin and other immune
      parameters among overweight or obese, but otherwise healthy postmenopausal women,
      perhaps because such effects are only present at low or deficient leptin
      concentrations.

PMID- 18614717
TI  - Flavonoids and cardiovascular health: which compounds, what mechanisms?

PMID- 18614716
TI  - Alternatives for macronutrient intake and chronic disease: a comparison of the
      OmniHeart diets with popular diets and with dietary recommendations.
AB  - BACKGROUND: Enhancements to current dietary advice to prevent chronic disease are
      of great clinical and public health importance. The OmniHeart Trial compared 3
      diets designed to reduce cardiovascular disease (CVD) risk-one high in
      carbohydrate and 2 that replaced carbohydrate with either unsaturated fat or
      protein. The lower carbohydrate diets improved the CVD risk factors. Several
      popular diets claiming health benefits emphasize carbohydrate, fat, or protein or
      various combined approaches. OBJECTIVE: The objective of this study was to
      compare the macronutrient contents of the OmniHeart trial diets to those of
      several popular diets and to evaluate each diet for consistency with national
      health guidelines. DESIGN: The macronutrient contents of 7-d menu plans from the
      OmniHeart Study, Dietary Approaches to Stop Hypertension (DASH), Zone, Atkins,
      Mediterranean, South Beach, and Ornish diets were evaluated for consistency with
      the US Food and Nutrition Board's Acceptable Macronutrient Distribution Ranges
      (AMDRs) and with the dietary recommendations of several health organizations.
      RESULTS: The OmniHeart diets fulfilled the major AMDRs, but, of the popular
      diets, only the Zone diet did. The OmniHeart diets were generally consistent with
      national guidelines to prevent cancer, diabetes, and heart disease, whereas most
      popular diets had limitations for fulfilling one or more guidelines. CONCLUSIONS:
      Although the OmniHeart protein and unsaturated fat diets were superior to the
      carbohydrate diet in improving CVD risk, all 3 study diets were consistent with
      national guidelines to reduce chronic disease risk, which suggests that the
      guidelines might now be fine-tuned to optimize disease prevention. Popular diets
      vary in their nutritional adequacy and consistency with guidelines for risk
      reduction.

PMID- 18614718
TI  - Defining dietary consumption: is the sum greater than its parts?

PMID- 18614719
TI  - Relation between alanine aminotransferase concentrations and visceral fat
      accumulation among nondiabetic overweight Korean women.
AB  - BACKGROUND: Alanine aminotransferase (ALT) is used as a surrogate marker for
      nonalcoholic fatty liver disease (NAFLD), which is frequently observed among
      obese subjects. Reported data were scanty about the relation between ALT
      concentrations and visceral fat accumulation measured by computed tomographic
      (CT) scanning in a large sample. OBJECTIVE: We investigated the association
      between ALT concentrations and visceral fat accumulation measured by CT scanning,
      among nondiabetic overweight Korean women. DESIGN: A cross-sectional study was
      performed in 903 nondiabetic overweight [body mass index (BMI; in kg/m(2)) > or =
      25] Korean women aged 20-80 y. The area of abdominal visceral adipose tissue
      (VAT) was measured by CT scan. Anthropometric and cardiometabolic variables were
      measured. RESULTS: Elevated ALT (> 40 IU/L) concentrations were found in 14.9% of
      the subjects. ALT concentrations were significantly correlated with all
      anthropometric and cardiometabolic variables after adjustment for age and alcohol
      consumption (P < 0.05). The adjusted odds ratios for elevated ALT concentrations
      according to the quartiles of VAT were 1.51 (95% CI: 0.83, 2.76), 3.16 (95% CI:
      1.55, 6.49), and 15.15 (95% CI: 4.57, 50.00) in the second (76.9-102.6 cm(2)),
      the third (102.7-135.0 cm(2)), and the fourth (135.1-382.7 cm(2)) quartiles,
      respectively, compared with the first quartile (23.0-76.8 cm(2)) (P for trend <
      0.001). In the multiple linear regression model, the VAT was significantly
      positively associated with ALT concentrations (standardized beta = 0.206, P <
      0.001), whereas the regression coefficients of other anthropometric and
      cardiometabolic variables were not significant. CONCLUSIONS: ALT concentrations
      have a strong association with visceral fat accumulation, and VAT is the main
      predictor of elevated ALT concentrations in the context of NAFLD among
      nondiabetic overweight Korean women.

PMID- 18614720
TI  - Appetite and adiposity in children: evidence for a behavioral susceptibility
      theory of obesity.
AB  - BACKGROUND: Pressures from the "obesogenic" environment are driving up obesity
      rates, but adiposity still varies widely within the population. Appetitive
      characteristics could underlie differences in susceptibility to the environment.
      OBJECTIVE: We examined associations between adiposity and 2 appetitive traits:
      satiety responsiveness and food cue responsiveness in children. DESIGN: Parents
      of 2 groups of children, 8-11-y-olds (n = 10 364) from a population-based twin
      cohort and 3-5-y-olds (n = 572) from a community sample, completed the Child
      Eating Behavior Questionnaire. Adiposity was indexed with body mass index (BMI;
      in kg/m(2)) SD scores. For the 8-11-y-olds, waist circumference was also recorded
      and used to derive waist SD scores. RESULTS: In both samples, higher BMI SD
      scores were associated with lower satiety responsiveness (8-11-y-olds: r = -0.22;
      3-5-y-olds: r = -0.19; P <0.001) and higher food cue responsiveness (r = 0.18 and
      0.18; P <0.001). In the twin sample, waist SD scores were associated with satiety
      responsiveness (r = -0.23, P < 0.001) and food cue responsiveness (r = 0.20, P <
      0.001). By analyzing the data by weight categories, children in higher weight and
      waist categories had lower satiety responsiveness and higher responsiveness to
      food cues in both samples (8-11-y-olds: both P < 0.001; 3-5-y-olds: both P <
      0.05), but the effect was more strongly linear in the older children. All
      associations remained significant, controlling for child age and sex and parental
      education and BMI. CONCLUSIONS: Associations between appetite and adiposity are
      consistent with a behavioral susceptibility model of obesity. Assessing appetite
      in childhood could help identify higher-risk children while they are still at a
      healthy weight, enabling targeted interventions to prevent obesity.

PMID- 18614721
TI  - Postprandial triglyceride responses to aerobic exercise and extended-release
      niacin.
AB  - BACKGROUND: Aerobic exercise and niacin are frequently used strategies for
      reducing serum triglycerides, and, yet, there is no information regarding the
      combined effects of these strategies on postprandial triglycerides. OBJECTIVE: We
      compared the effects of aerobic exercise and 6 wk of extended-release niacin on
      postprandial triglycerides in men with the metabolic syndrome. DESIGN: Fifteen
      participants underwent each of 4 conditions: control--high-fat meal only (100 g
      fat); exercise--aerobic exercise performed 1 h before a high-fat meal; niacin-
      high-fat meal consumed after 6 wk of niacin; and niacin + exercise--high-fat meal
      consumed after 6 wk of niacin and 1 h after aerobic exercise. Temporal responses
      for triglyceride and insulin concentrations were measured and total (AUC(T)) and
      incremental (AUC(I)) areas under the curve were calculated. Differences were
      determined by using a 2-factor repeated-measures analysis of variance (P < 0.05
      for all). RESULTS: Exercise lowered the triglyceride AUC(I) by 32% compared with
      control (724 +/- 118 and 1058 +/- 137, respectively). Niacin had no influence on
      the triglyceride AUC(I) and attenuated the triglyceride-lowering effect of
      exercise when combined. Niacin + exercise had no effect on the triglyceride
      AUC(I) but decreased the insulin AUC(I) after niacin administration. CONCLUSIONS:
      Aerobic exercise lowers the postprandial triglyceride response to a high-fat
      meal. Niacin lowers fasting but not postprandial triglycerides and appears to
      influence the triglyceride-lowering effect of aerobic exercise when combined.
      However, exercise decreases postprandial insulin concentrations after niacin
      administration, which illustrates the potential metabolic benefits of exercise in
      persons taking niacin.

PMID- 18614722
TI  - Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: The beneficial effects of flavonoid consumption on cardiovascular
      risk are supported by mechanistic and epidemiologic evidence. OBJECTIVE: We aimed
      to systematically review the effectiveness of different flavonoid subclasses and
      flavonoid-rich food sources on cardiovascular disease (CVD) and risk factors--ie,
      lipoproteins, blood pressure, and flow-mediated dilatation (FMD). DESIGN: Methods
      included a structured search strategy on MEDLINE, EMBASE, and Cochrane databases;
      formal inclusion or exclusion, data extraction, and validity assessment; and meta
      analysis. RESULTS: One hundred thirty-three trials were included. No randomized
      controlled trial studied effects on CVD morbidity or mortality. Significant
      heterogeneity confirmed differential effects between flavonoid subclasses and
      foods. Chocolate increased FMD after acute (3.99%; 95% CI: 2.86, 5.12; 6 studies)
      and chronic (1.45%; 0.62, 2.28; 2 studies) intake and reduced systolic (-5.88 mm
      Hg; -9.55, -2.21; 5 studies) and diastolic (-3.30 mm Hg; -5.77, -0.83; 4 studies)
      blood pressure. Soy protein isolate (but not other soy products or components)
      significantly reduced diastolic blood pressure (-1.99 mm Hg; -2.86, -1.12; 9
      studies) and LDL cholesterol (-0.19 mmol/L; -0.24, -0.14; 39 studies). Acute
      black tea consumption increased systolic (5.69 mm Hg; 1.52, 9.86; 4 studies) and
      diastolic (2.56 mm Hg; 1.03, 4.10; 4 studies) blood pressure. Green tea reduced
      LDL (-0.23 mmol/L; -0.34, -0.12; 4 studies). For many of the other flavonoids,
      there was insufficient evidence to draw conclusions about efficacy. CONCLUSIONS:
      To date, the effects of flavonoids from soy and cocoa have been the main focus of
      attention. Future studies should focus on other commonly consumed subclasses (eg,
      anthocyanins and flavanones), examine dose-response effects, and be of long
      enough duration to allow assessment of clinically relevant endpoints.

PMID- 18614723
TI  - Endothelial function after high-sugar-food ingestion improves with endurance
      exercise performed on the previous day.
AB  - BACKGROUND: Endothelial function deteriorates after glucose ingestion. This may
      be attributed to hyperglycemia-induced oxidative stress. Acute endurance exercise
      might improve postprandial endothelial function by enhancing glucoregulation and
      reducing postprandial hyperglycemia. OBJECTIVE: The objective was to determine
      whether endurance exercise performed 17 h before high-sugar-food ingestion
      attenuates postprandial impairment in endothelial function. DESIGN: Healthy men
      and women (n = 13; age: 48 +/- 17 y) were studied on 2 occasions: after > or = 48
      h with no exercise and 17 h after a 60-min bout of endurance exercise. During
      each trial, brachial artery flow mediated dilation (FMD) was used to assess
      endothelial function before and after the ingestion of a candy bar and soft
      drink. Glucose, insulin, and thiobarbituric acid-reactive substances (TBARS), a
      marker of oxidative stress, were measured in blood obtained during each FMD
      measurement. The insulin sensitivity index was calculated from the glucose and
      insulin data. RESULTS: FMD decreased significantly after food ingestion in both
      trials. However, prior exercise shifted the entire FMD curve upward (main
      treatment effect: P = 0.0002), which resulted in a greater area under the curve
      for FMD (774 +/- 122%.min) than did no exercise (607 +/- 122%.min) (P = 0.01).
      Prior exercise shifted the glucose and insulin curves downward (main treatment
      effects: P = 0.05 and P = 0.0007, respectively) and resulted in a significantly
      greater insulin sensitivity index (10.8 +/- 0.7) than did no exercise (9.2 +/-
      0.7) (P = 0.01). TBARS did not differ significantly between trials. CONCLUSION:
      Postprandial endothelial function was improved by endurance exercise performed
      approximately 17 h earlier. This effect was accompanied by exercise-induced
      improvements in insulin action and reductions in glycemia, but did not correspond
      with reductions in oxidative stress, as assessed by TBARS.

PMID- 18614724
TI  - Acute dark chocolate and cocoa ingestion and endothelial function: a randomized
      controlled crossover trial.
AB  - BACKGROUND: Studies suggest cardioprotective benefits of dark chocolate
      containing cocoa. OBJECTIVE: This study examines the acute effects of solid dark
      chocolate and liquid cocoa intake on endothelial function and blood pressure in
      overweight adults. DESIGN: Randomized, placebo-controlled, single-blind crossover
      trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)):
      30]. In phase 1, subjects were randomly assigned to consume a solid dark
      chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar
      (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to
      consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa
      (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder).
      RESULTS: Solid dark chocolate and liquid cocoa ingestion improved endothelial
      function (measured as flow-mediated dilatation) compared with placebo (dark
      chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P < 0.001; sugar-free and
      sugared cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P <
      0.001). Blood pressure decreased after the ingestion of dark chocolate and sugar
      free cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg
      compared with 2.7 +/- 6.6 mm Hg; P < 0.001; and diastolic, -1.4 +/- 3.9 mm Hg
      compared with 2.7 +/- 6.4 mm Hg; P = 0.01; sugar-free cocoa: systolic, -2.1 +/-
      7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P < 0.001; and diastolic: -1.2 +/- 8.7
      mm Hg compared with 2.8 +/- 5.6 mm Hg; P = 0.014). Endothelial function improved
      significantly more with sugar-free than with regular cocoa (5.7 +/- 2.6% compared
      with 2.0 +/- 1.8%; P < 0.001). CONCLUSIONS: The acute ingestion of both solid
      dark chocolate and liquid cocoa improved endothelial function and lowered blood
      pressure in overweight adults. Sugar content may attenuate these effects, and
      sugar-free preparations may augment them.

PMID- 18614726
TI  - Selenium status of term infants fed selenium-supplemented formula in a randomized
      dose-response trial.
AB  - BACKGROUND: The optimal form and dose of selenium supplementation required to
      achieve indicators of selenium status equivalent to those in breastfed infants
      are unclear. OBJECTIVE: The objective was to evaluate the effect of fortifying
      infant formula (6 microg Se/L) with 2 concentrations of selenate (7 and 15
      microg/L) on biochemical indicators of selenium status and growth at 16 wk in
      term infants. DESIGN: A randomized dose-response trial was conducted in 3 groups
      of term infants fed formula with different selenium concentrations [6 microg/L,
      F+0 (control); 13 microg/L, F+7; and 21 microg/L, F+15] and in a parallel
      breastfed reference group (BF; 11 +/- 2 microg Se/L). RESULTS: One hundred sixty
      one (47% males) infants completed the 16-wk study. Baseline plasma selenium was
      0.3 +/- 0.1 micromol/L. At 16 wk, plasma selenium had increased in all groups (P
      < 0.001) and was greater (P < 0.01) in the F+7 and F+15 groups and lower (P <
      0.05) in the F+0 group than in the BF group. Plasma glutathione peroxidase
      increased in the F+15 group, decreased in the F+0 group, and, at 16 wk, was lower
      in the F+0 group than in the other groups (all P < 0.05). Erythrocyte selenium
      and glutathione peroxidase decreased in all groups (P < 0.05), but the magnitude
      of the change was greater in the F+0 than in the F+15 group (P < 0.05). There was
      no effect of selenium supplementation on growth. CONCLUSIONS: Selenate
      fortification of formula resulted in an increase in plasma indicators of selenium
      status relative to indicators observed in infants fed low-selenium-containing
      formula. Although the erythrocyte indicators decreased in all groups, the 21
      microg/L dose (F+15 group) resulted in a smaller decrease and in higher
      erythrocyte selenium than did the standard formula. Supplementation of low
      selenium formula to provide a net selenium concentration close to that found in
      the breast milk of US women (18 microg/L) may be justified.

PMID- 18614725
TI  - Modifications to the Healthy Eating Index and its ability to predict obesity: the
      Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: The Healthy Eating Index (HEI) is a measure of diet quality developed
      based on the Dietary Guidelines for Americans (DGA). OBJECTIVE: The objective was
      to assess the diet quality of a multi-ethnic population using and comparing the 2
      HEIs, the updated HEI (HEI-05) based on the 2005 DGA and the original 1990 HEI
      (HEI-90), with the objective of predicting obesity outcomes. DESIGN: A
      longitudinal analysis of survey and clinical data from 6236 middle-aged and
      elderly white, African American, Hispanic, and Chinese participants of the Multi
      Ethnic Study of Atherosclerosis (MESA) was conducted. Baseline diet quality was
      assessed with the use of HEI-90 and HEI-05. Baseline and 18-mo follow-up body
      mass index (BMI) and waist circumference (WC) data were predicted by using z
      score multiple regression models, and categorical obesity status was predicted by
      using multinomial logistic regression. RESULTS: Overall, the HEI-05 had larger z
      score beta coefficients than did the HEI-90 (eg, in whites, -0.53 compared with 
      0.48 in baseline BMI, -0.54 compared with -0.47 in follow-up BMI, -1.67 compared
      with -1.56 in baseline WC, and -1.57 compared with -1.44 in follow-up WC). Among
      whites only, both HEIs were significant predictors of BMI and WC (all P < 0.001).
      The odds of being obese rather than normal weight were inversely related to HEI z
      scores primarily in whites (P < 0.05). CONCLUSIONS: The changes to the 2005 DGA,
      as reflected by HEI-05, appear to better predict obesity outcomes in this multi
      ethnic population, primarily in whites. Additional research on ethnic-specific
      DGA adherence and its relation to health outcomes is needed.

PMID- 18614727
TI  - Bolus tube feeding suppresses food intake and circulating ghrelin concentrations
      in healthy subjects in a short-term placebo-controlled trial.
AB  - BACKGROUND: Previous investigations suggest continuous tube feeding (TF)
      schedules do not suppress appetite and food intake, but bolus TF has been little
      studied. OBJECTIVE: We tested the hypothesis that 1) bolus TF does not suppress
      appetite and food intake and 2) there is no interrelation between food intake and
      appetite mediators (including ghrelin). DESIGN: A single-blind, placebo
      controlled trial within which 6 healthy men [body mass index (in kg/m(2)): 21.1
      +/- 1.61] received 3 d of bolus TF (6.93 +/- 0.38 MJ/d of 4.18 kJ/mL
      multinutrient feed). For 2 d before and after TF, placebo boluses (<0.4 MJ/d)
      were given by tube. Hourly tracking of appetite, weighed measurements of daily ad
      libitum food intake, and metabolic and hormonal (including ghrelin) measurements
      were undertaken. RESULTS: Total energy intake was significantly increased with
      bolus TF (18.2 +/- 1.86 MJ; P = 0.0005) despite a partial reduction in food
      intake compared with placebo periods (P = 0.013) and during the TF period (by
      15%; P = 0.007). There was little change in hunger and fullness with bolus TF,
      and within-day temporal patterns did not differ whether TF or placebo was given.
      Changes in fasting concentrations of ghrelin (1003.6-756.0 pmol/L; P = 0.013) and
      other mediators (including leptin, insulin, and glucose) were significantly
      related to subsequent daily food intake (eg, ghrelin: r(2) = 0.81, P = 0.022).
      CONCLUSIONS: In this short-term study, subjects maintained appetite ratings
      during bolus TF by a significant reduction in food intake and changes in ghrelin
      and some appetite mediators related to subsequent daily food intake. Longer-term
      studies are required to fully ascertain the effect of TF on appetite, food
      intake, and appetite mediators.

PMID- 18614728
TI  - Effects of energy density and feeding frequency of complementary foods on total
      daily energy intakes and consumption of breast milk by healthy breastfed
      Bangladeshi children.
AB  - BACKGROUND: Information is needed on the minimum energy density and feeding
      frequency of complementary foods that can provide adequate energy intakes (EIs)
      for healthy breastfed children. OBJECTIVES: The objectives of the study were to
      evaluate the effects of various energy densities and feeding frequencies of
      complementary foods on EI from these foods, breast milk consumption, and total EI
      from both sources. DESIGN: During 9 separate, randomly ordered dietary periods
      lasting 3-6 d each, we measured intakes of food and breast milk by 18 healthy
      breastfed children 8-11 mo of age who, 3, 4, or 5 times/d, were fed porridge with
      a coded energy density of 0.5, 1.0, or 1.5 kcal/g. Food intake was measured by
      weighing the feeding bowl before and after meals, and breast milk intake was
      measured by test weighing. RESULTS: The mean amounts of complementary foods
      consumed were inversely related to their energy density and positively related to
      the number of meals/d (P < 0.001 for both); EIs from foods were positively
      related to both factors. Breast milk intake decreased slightly but progressively,
      with greater energy density and feeding frequency of complementary foods; total
      EIs (kcal/d) increased in relation to both factors (P < 0.001 for both).
      CONCLUSIONS: The energy density and feeding frequency of complementary foods
      affect infants' total daily EI and breast milk consumption. Recommendations can
      be developed for the appropriate combinations of these dietary factors that are
      compatible with adequate EI, although longer-term effects of complementary
      feeding practices on breast milk intake and breastfeeding duration need further
      community-based studies.

PMID- 18614729
TI  - Lifestyle factors associated with age-related differences in body composition:
      the Florey Adelaide Male Aging Study.
AB  - BACKGROUND: Age-related change in body composition is associated with adverse
      health outcomes, including functional decline, disability, morbidity, and early
      mortality. Prevention of age-related changes requires a greater understanding of
      the associations among age, lifestyle factors, and body composition. OBJECTIVE:
      We aimed to comprehensively determine lifestyle factors associated with age
      related differences in body composition assessed by using dual-energy X-ray
      absorptiometry. DESIGN: We analyzed baseline (cross-sectional) data collected
      from 2002 to 2005 for approximately 1200 men in the Florey Adelaide Male Aging
      Study, a regionally representative cohort of Australian men aged 35-81 y.
      RESULTS: Mean values for whole-body lean mass (LM) and areal bone mineral density
      (aBMD) decreased, whereas mean values for abdominal fat mass (FM) and whole-body
      and abdominal percentage FM (%FM) increased with age. No significant age-related
      differences were found for whole-body FM. Multiple adjusted odds of being in the
      highest tertiles for whole-body and abdominal %FM decreased for smokers (63-71%)
      but increased with age group and for lowest energy (43-50%), carbohydrate (92
      107%), and fiber (107%) intake tertiles. Multiple adjusted odds of being in the
      highest aBMD tertile decreased for lowest body mass (92%) and carbohydrate intake
      (63%) tertiles and for men aged > or = 75 y (78%) but increased for Australian
      birth (58%) and for participation in vigorous physical activities (82%).
      CONCLUSIONS: Age-related differences in body composition indicate that whole-body
      FM remains stable but increases viscerally and that whole-body %FM is confounded
      by LM, whereas aBMD decreases with age. Age-related differences in %FM and aBMD
      are associated with demographic and lifestyle factors.

PMID- 18614730
TI  - Folate and cobalamin status in relation to breastfeeding and weaning in healthy
      infants.
AB  - BACKGROUND: Folate and cobalamin status changes markedly during infancy.
      OBJECTIVE: We aimed to examine the influence of breastfeeding on folate and
      cobalamin status in healthy infants. DESIGN: In a longitudinal study, we measured
      serum folate, cobalamin, holotranscobalamin, holohaptocorrin, methylmalonic acid,
      and homocysteine at birth and at ages 6, 12, and 24 mo (n = 361, 262, 244, and
      224, respectively). Breastfeeding status and nutrient intake were assessed by
      using questionnaires and 7-d weighed-food records (at 12 mo). RESULTS: All
      indexes changed significantly from birth to age 24 mo (P < 0.001). Folate was
      high until age 6 mo and then declined. At age 6 mo, folate was positively
      correlated with duration of exclusive breastfeeding (rho = 0.29; P < 0.001).
      Cobalamin status declined after birth in breastfed but increased in nonbreastfed
      infants. Thus, holotranscobalamin (pmol/L) was lower in breastfed than in
      nonbreastfed children at age 6 mo [geometric mean: 37 (95% CI: 33, 40) and 74
      (64, 86), respectively], at 12 mo [51 (46, 56) and 76 (70, 82), respectively],
      and at 24 mo [65 (50, 83) and 90 (85, 97), respectively; P < 0.05 for all].
      Complementary feeding did not increase (6 mo) or modestly increased (12 mo)
      cobalamin status in breastfed children. At 12 mo, cobalamin intake (microg/d),
      excluding breast milk cobalamin, was lower in breastfed than in nonbreastfed
      infants [geometric mean: 1.4 (1.3, 1.6) and 2.4 (2.1, 2.6), respectively; P <
      0.001]. However, after adjustment for total cobalamin intake, cobalamin status
      (ie, holotranscobalamin) remained significantly lower in breastfed than in
      nonbreastfed infants [54 (49, 59) and 70 (64, 78), respectively; P < 0.001].
      CONCLUSIONS: Low cobalamin status is a characteristic finding in breastfed
      children. Reference limits according to age and breastfeeding status should be
      considered in early childhood.

PMID- 18614731
TI  - Total sulfur amino acid requirement and metabolism in parenterally fed
      postsurgical human neonates.
AB  - BACKGROUND: Except for tyrosine, the amino acid requirements of human neonates
      receiving parenteral nutrition (PN) have not been experimentally derived.
      OBJECTIVES: The objectives were to determine the total sulfur amino acid (TSAA)
      requirement (methionine in the absence of cysteine) of postsurgical, PN-fed human
      neonates by using the indicator amino acid oxidation (IAAO) technique with L-[1
      (13)C]phenylalanine as the indicator. DESIGN: Fifteen postsurgical neonates were
      randomly assigned to receive 1 of 18 methionine intakes ranging from 10 to 120 mg
      x kg(-1) x d(-1), delivered in a customized, cysteine-free amino acid solution.
      Breath and urine samples were collected for the measurement of (13)CO(2) and
      amino acid enrichment. Blood samples were collected at baseline and after the
      test methionine infusion for the measurement of plasma methionine, homocysteine,
      cystathionine, and cysteine concentrations. RESULTS: Breakpoint analysis
      determined the mean TSAA requirements to be 47.4 (95% CI: 38.7, 56.1) and 49.0
      (95% CI: 39.9, 58.0) mg x kg(-1) x d(-1) with the use of oxidation and
      F(13)CO(2), respectively. CONCLUSIONS: This is the first study to report the TSAA
      requirement of postsurgical, PN-fed human neonates. The estimated methionine
      requirement expressed as a proportion of the methionine content of current
      commercial pediatric PN solutions was 90% (range: 48-90%) of that found in the
      lowest methionine-containing PN solution.

PMID- 18614732
TI  - Gene expression profiling of human skeletal muscle in response to stabilized
      weight loss.
AB  - BACKGROUND: Diet-induced weight reduction promotes a decrease in resting energy
      expenditure that could partly explain the difficulty in maintaining reduced body
      mass. Whether this reduction remains after stabilized weight loss is still
      controversial, and the molecular mechanisms are unknown. OBJECTIVE: The objective
      was to investigate the effect of a stabilized 10% weight loss on body
      composition, metabolic profile, and skeletal muscle gene expression profiling.
      DESIGN: Obese women were assigned to a 4-wk very-low-calorie diet, a 3-6-wk low
      calorie diet, and a 4-wk weight-maintenance program to achieve a 10% weight loss.
      Resting energy expenditure, body composition, plasma variables, and skeletal
      muscle transcriptome were compared before weight loss and during stabilized
      weight reduction. RESULTS: Energy restriction caused an 11% weight loss.
      Stabilization to the new weight was accompanied by an 11% decrease in the resting
      metabolic rate normalized to the body cellular mass. A large number of genes were
      regulated with a narrow range of regulation. The main regulated genes were
      slow/oxidative fiber markers, which were overexpressed, and the gene encoding the
      glucose metabolism inhibitor PDK4, which tended to be down-regulated. The
      knowledge-based approach gene set enrichment analysis showed that a set of genes
      related to long-term calorie restriction was up-regulated, whereas sets of genes
      related to insulin, interleukin 6, and ubiquitin-mediated proteolysis were down
      regulated. CONCLUSIONS: Weight loss-induced decreases in resting metabolic rate
      persist after weight stabilization. Changes in skeletal muscle gene expression
      indicate a shift toward oxidative metabolism.

PMID- 18614734
TI  - Relation between pyridoxal and pyridoxal phosphate concentrations in plasma, red
      cells, and white cells in patients with critical illness.
AB  - BACKGROUND: Evidence suggests that the relation between plasma and red cell
      vitamin B-6 concentrations is perturbed as part of the systemic inflammatory
      response in critically ill patients. OBJECTIVE: The aim was to examine the cross
      sectional and longitudinal interrelations between pyridoxal (PL) and pyridoxal
      phosphate (PLP) concentrations in plasma and red and white cells in patients with
      critical illness. DESIGN: PLP and PL concentrations were measured by HPLC in
      plasma and red and white cells in normal subjects (n = 126) and critically ill
      patients (n = 96) on admission and on follow-up. RESULTS: On admission, compared
      with the controls, median plasma PLP and PL (P < 0.001 and < 0.01, respectively)
      and red cell PLP and PL (P < 0.001 and < 0.05, respectively) and their ratio
      (PLP:PL) in plasma and red cells (P < 0.001 and < 0.01, respectively) were
      significantly lower in the critically ill. In critically ill patients, plasma
      PLP:PL was significantly lower than red cell PLP:PL (P = 0.001) and white cell
      PLP:PL (P = 0.008). Plasma PL concentration was directly associated with both red
      cell PL (r(s) = 0.73, P < 0.001) and white cell PL (r(s) = 0.68, P < 0.001). Red
      cell PL and white cell PL were directly associated with red cell PLP (r(s) =
      0.82, P < 0.001) and white cell PLP (r(s) = 0.68, P < 0.001), respectively.
      Longitudinal measurements (n = 48) were similar. CONCLUSIONS: The relation
      between plasma PLP and PL was significantly perturbed in critical illness. This
      effect was less pronounced in red and white cells. Therefore, these results
      confirm the hypothesis that intracellular PLP concentrations are more likely to
      be a reliable measure of status than are plasma measurements in the critically
      ill patient.

PMID- 18614733
TI  - Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors.
AB  - BACKGROUND: Little is known about vitamin D status in breast cancer survivors.
      This issue is important because vitamin D influences pathways related to
      carcinogenesis. OBJECTIVE: The objective of this report was to describe and
      understand vitamin D status in a breast cancer survivor cohort. DESIGN: Data are
      from the Health, Eating, Activity, and Lifestyle study. With the use of a cross
      sectional design, we examined serum concentrations of 25-hydroxyvitamin D
      [25(OH)D] in 790 breast cancer survivors from western Washington state, New
      Mexico, and Los Angeles County. Cancer treatment data were obtained from
      Surveillance, Epidemiology, and End Results registries and medical records.
      Fasting blood, anthropometry, and lifestyle habits were collected after diagnosis
      and treatment. We examined distributions of 25(OH)D by race-ethnicity, season,
      geography, and clinical characteristics. Multivariate regression tested
      associations between 25(OH)D and stage of disease. RESULTS: Five hundred ninety
      seven (75.6%) of the women had low serum 25(OH)D, suggesting vitamin D
      insufficiency or frank deficiency. The overall mean (+/-SD) was 24.8 +/- 10.4
      ng/mL, but it was lower for African Americans (18.1 +/- 8.7 ng/mL) and Hispanics
      (22.1 +/- 9.2 ng/mL). Women with localized (n = 424) or regional (n = 182) breast
      cancer had lower serum 25(OH)D than did women with in situ disease (n = 184) (P =
      0.05 and P = 0.03, respectively). Multivariate regression models controlled for
      age, body mass index (in kg/m(2)), race-ethnicity, geography, season, physical
      activity, diet, and cancer treatments showed that stage of disease independently
      predicted serum 25(OH)D (P = 0.02). CONCLUSIONS: In these breast cancer
      survivors, the prevalence of vitamin D insufficiency was high. Clinicians might
      consider monitoring vitamin D status in breast cancer patients, together with
      appropriate treatments, if necessary.

PMID- 18614735
TI  - Association between short interpregnancy intervals and term birth weight: the
      role of folate depletion.
AB  - BACKGROUND: Maternal folate depletion has been proposed as a primary explanation
      for the excess risk of fetal growth restriction associated with short
      interpregnancy intervals. OBJECTIVE: We aimed to evaluate the folate depletion
      hypothesis in a community-based cohort of pregnant women. DESIGN: Using a
      subsample of the cohort (multiparous participants who delivered a liveborn
      singleton infant, n = 3153), we investigated the relation between an increase in
      the interpregnancy interval (from 1 to 24 mo, natural log transformation) and
      birth weight and the risk of small-for-gestational-age (SGA) in 3 strata of
      maternal periconceptional folic acid use: nonuse, late use (begun after
      conception), and early use (begun before conception). RESULTS: Each increase in
      the interpregnancy interval on the natural log (ln) scale was associated with a
      mean (+/-SE) increase of 63.1 +/- 20.3 g in birth weight (P = 0.002). This
      relation was mitigated by folic acid use: the change in birth weight was
      increases of 165.2 +/- 39.6 g for nonuse (P < 0.001) and 33.5 +/- 35.6 g for late
      use (P = 0.347) and a decrease of 5.9 +/- 33.6 g for early use (P = 0.861). The
      birth weight differences were directly translated into SGA risk. Odds ratios per
      1-mo increase in ln(interpregnancy interval) were significant for the total group
      (0.61; 95% CI: 0.46, 0.82) and for nonuse (0.38; 0.24, 0.60) and nonsignificant
      for late (0.83; 0.48, 1.44) and early (1.28; 0.58, 2.84) use. CONCLUSIONS: Folate
      depletion apparently contributes to the excess risk of fetal growth restriction
      that is associated with short interpregnancy intervals. As a preventive option,
      postnatal supplementation may be beneficial, but confirmation is needed.

PMID- 18614736
TI  - Maternal zinc supplementation and growth in Peruvian infants.
AB  - BACKGROUND: Little is known about how maternal zinc intake influences growth in
      utero and in postnatal life in humans. OBJECTIVE: We aimed to assess the effect
      of maternal zinc supplementation during pregnancy on infant growth through age 1
      y. DESIGN: A double-blind, randomized controlled trial of prenatal zinc
      supplementation was conducted from 1995 to 1997 in Lima, Peru. Women (n = 1295)
      were enrolled at 15.6 +/- 4.6 wk gestation and assigned to receive daily
      supplements with zinc (15 mg Zn + 60 mg Fe + 250 microg folic acid) or without
      zinc (60 Fe + 250 microg folic acid) through pregnancy to 1 mo after delivery. At
      birth, 546 infants were followed for 12 mo to assess growth. Anthropometric
      measures of body size and composition were collected monthly, and morbidity and
      dietary intake surveillance was carried out weekly. RESULTS: No differences in
      maternal socioeconomic characteristics by treatment group or follow-up period
      were found. Infants born to mothers prenatally supplemented with zinc had
      significantly (P < 0.05) larger average growth measures beginning in month 4 and
      continuing through month 12. In longitudinal regression modeling, prenatal zinc
      was associated with greater weight (by 0.58 +/- 0.12 kg; P < 0.001), calf
      circumference (by 1.01 +/- 0.21 cm; P < 0.001), chest circumference (by 0.60 +/-
      0.20 cm; P = 0.002), and calf muscle area (by 35.78 +/- 14.75 mm(2); P = 0.01)
      after adjustment for a range of covariates. No effect was observed for linear
      growth. CONCLUSION: Maternal zinc supplementation in this population was
      associated with offspring growth, which is suggestive of lean tissue mass
      accretion.

PMID- 18614737
TI  - Classification of malnutrition in cystic fibrosis: implications for evaluating
      and benchmarking clinical practice performance.
AB  - BACKGROUND: In 2005, the Cystic Fibrosis Foundation (CFF) revised the nutrition
      classification guidelines to eliminate the use of percentage of ideal body weight
      (%IBW) to define "nutritional failure"; the CFF also recommended that children
      with cystic fibrosis maintain a body mass index percentile (BMIp) > or = 50th.
      OBJECTIVE: We assessed the effect of the 2005 CFF nutrition classification
      guidelines on evaluating the performance of nutritional care practices. DESIGN:
      Data from 14,702 children reported to the 2002 CFF Patient Registry were analyzed
      to compare malnutrition rates in 113 cystic fibrosis centers in the United
      States. Nutritional failure was defined according to the 2002 CFF criteria--ie,
      height < 5th percentile, %IBW < 90%, or BMIp < 10th. "Below BMI goal" was defined
      according to the 2005 CFF criterion, ie BMIp < 50th. RESULTS: Eliminating %IBW
      resulted in a 6% reduction (from 33% to 27%) in the nutritional failure rate in
      the United States. The use of BMIp < 50th led to the classification of 57% of
      children as below the BMI goal. Misclassification of nutritional failure
      according to %IBW ranged from 1% to 16% among 113 centers and was greater in the
      centers with a larger proportion of tall patients. After the elimination of %IBW,
      one-third of centers changed to a different tertile ranking for nutritional
      failure rates (kappa = 0.50, moderate-to-poor agreement). More than half the
      centers changed to a different tertile ranking, from nutritional failure to below
      BMI goal (kappa = 0.22, poor agreement). CONCLUSION: Eliminating
      misclassification by %IBW and implementing the new BMI goal led to profound and
      unequal changes in malnutrition rates across cystic fibrosis centers.

PMID- 18614738
TI  - Fish oil intake compared with olive oil intake in late pregnancy and asthma in
      the offspring: 16 y of registry-based follow-up from a randomized controlled
      trial.
AB  - BACKGROUND: Evidence suggests that asthma is rooted in the intrauterine
      environment and that intake of marine n-3 polyunsaturated fatty acids (n-3 PUFAs)
      in pregnancy may have immunomodulatory effects on the child. OBJECTIVE: Our aim
      was to examine whether increasing maternal intake of n-3 PUFAs in pregnancy may
      affect offspring risk of asthma. DESIGN: In 1990, a population-based sample of
      533 women with normal pregnancies were randomly assigned 2:1:1 to receive four 1
      g gelatin capsules/d with fish oil providing 2.7 g n-3 PUFAs (n = 266); four 1-g,
      similar-looking capsules/d with olive oil (n = 136); or no oil capsules (n =
      131). Women were recruited and randomly assigned around gestation week 30 and
      asked to take capsules until delivery. Among 531 live-born children, 528 were
      identified in registries and 523 were still alive by August 2006. Diagnoses from
      the International Coding of Diseases version 10 were extracted from a mandatory
      registry that recorded diagnoses reported from hospital contacts. RESULTS: During
      the 16 y that passed since childbirth, 19 children from the fish oil and olive
      oil groups had received an asthma-related diagnosis; 10 had received the
      diagnosis allergic asthma. The hazard rate of asthma was reduced by 63% (95% CI:
      8%, 85%; P = 0.03), whereas the hazard rate of allergic asthma was reduced by 87%
      (95% CI: 40%, 97%; P = 0.01) in the fish oil compared with the olive oil group.
      CONCLUSION: Under the assumption that intake of olive oil in the dose provided
      here was inert, our results support that increasing n-3 PUFAs in late pregnancy
      may carry an important prophylactic potential in relation to offspring asthma.

PMID- 18614739
TI  - Dietary patterns as identified by factor analysis and colorectal cancer among
      middle-aged Americans.
AB  - BACKGROUND: Although diet has long been suspected as an etiological factor for
      colorectal cancer, studies of single foods and nutrients have provided
      inconsistent results. OBJECTIVE: We used factor analysis methods to study
      associations between dietary patterns and colorectal cancer in middle-aged
      Americans. DESIGN: Diet was assessed among 293,615 men and 198,767 women in the
      National Institutes of Health-AARP Diet and Health Study. Principal components
      factor analysis identified 3 primary dietary patterns: a fruit and vegetables, a
      diet foods, and a red meat and potatoes pattern. State cancer registries
      identified 2151 incident cases of colorectal cancer in men and 959 in women
      between 1995 and 2000. RESULTS: Men with high scores on the fruit and vegetable
      pattern were at decreased risk [relative risk (RR) for quintile (Q) 5 versus Q1:
      0.81; 95% CI: 0.70, 0.93; P for trend = 0.004]. Both men and women had a similar
      risk reduction with high scores on the diet food factor: men (RR: 0.82; 95% CI:
      0.72, 0.94; P for trend = 0.001) and women (RR: 0.87; 95% CI: 0.71, 1.07; P for
      trend = 0.06). High scores on the red meat factor were associated with increased
      risk: men (RR: 1.17; 95% CI: 1.02, 1.35; P for trend = 0.14) and women (RR: 1.48;
      95% CI: 1.20, 1.83; P for trend = 0.0002). CONCLUSIONS: These results suggest
      that dietary patterns characterized by a low frequency of meat and potato
      consumption and frequent consumption of fruit and vegetables and fat-reduced
      foods are consistent with a decreased risk of colorectal cancer.

PMID- 18614741
TI  - Relations between dietary sodium and potassium intakes and mortality from
      cardiovascular disease: the Japan Collaborative Cohort Study for Evaluation of
      Cancer Risks.
AB  - BACKGROUND: Limited evidence is available about the relations between sodium and
      potassium intakes and cardiovascular disease in the general population.
      OBJECTIVE: The objective was to investigate relations between sodium and
      potassium intakes and cardiovascular disease in Asian populations whose mean
      sodium intake is generally high. DESIGN: Between 1988 and 1990, a total of 58,730
      Japanese subjects (n = 23,119 men and 35,611 women) aged 40-79 y with no history
      of stroke, coronary heart disease, or cancer completed a lifestyle questionnaire
      including food intake frequency under the Japan Collaborative Cohort Study for
      Evaluation of Cancer Risk sponsored by the Ministry of Education, Sports and
      Science. RESULTS: After 745,161 person-years of follow-up, we documented 986
      deaths from stroke (153 subarachnoid hemorrhages, 227 intraparenchymal
      hemorrhages, and 510 ischemic strokes) and 424 deaths from coronary heart
      disease. Sodium intake was positively associated with mortality from total
      stroke, ischemic stroke, and total cardiovascular disease. The multivariable
      hazard ratio for the highest versus the lowest quintiles of sodium intake after
      adjustment for age, sex, and cardiovascular disease risk factors was 1.55 (95%
      CI: 1.21, 2.00; P for trend < 0.001) for total stroke, 2.04 (95% CI: 1.41, 2.94;
      P for trend < 0.001) for ischemic stroke, and 1.42 (95% CI: 1.20, 1.69; P for
      trend < 0.001) for total cardiovascular disease. Potassium intake was inversely
      associated with mortality from coronary heart disease and total cardiovascular
      disease. The multivariable hazard ratio for the highest versus the lowest
      quintiles of potassium intake was 0.65 (95% CI: 0.39, 1.06; P for trend = 0.083)
      for coronary heart disease and 0.73 (95% CI: 0.59, 0.92; P for trend = 0.018) for
      total cardiovascular disease, and these associations were more evident for women
      than for men. CONCLUSIONS: A high sodium intake and a low potassium intake may
      increase the risk of mortality from cardiovascular disease.

PMID- 18614740
TI  - A priori-defined dietary patterns and markers of cardiovascular disease risk in
      the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: The level of detail regarding the dietary intake necessary to
      characterize associations between diet and cardiovascular disease (CVD) risk is
      uncertain. OBJECTIVE: We evaluated a unique a priori-defined dietary pattern in
      relation to several traditional and novel CVD risk factors. DESIGN: At the
      baseline examination, diet (by food-frequency questionnaire), markers of
      inflammation, subclinical atherosclerosis, renal disease, vascular compliance,
      and other traditional risk factors were measured in 5089 men and women aged 45-84
      y without clinical CVD or diabetes from the Multi-Ethnic Study of Atherosclerosis
      (MESA). We defined a Comprehensive Healthy Dietary Pattern by summing weighted
      categorical ranks of 36 narrowly defined food groups (21 rated favorably with
      categorical ranks x +1.0 and 15 rated unfavorably with categorical ranks x -1.0).
      We also defined a Simplified Healthy Dietary Pattern composed of 3 favorable
      (whole grains, fruit, and seeds and nuts) and 3 unfavorable (added fats and oils,
      processed meats, and fried potatoes) food groups using similar scoring techniques
      and determined the difference between the comprehensive and simplified scores.
      RESULTS: The Comprehensive Healthy Dietary Pattern was associated with lower
      urinary albumin:creatinine ratios, common carotid intima-media thickness,
      measures of adiposity, and inflammatory marker, triacylglycerol, and insulin
      concentrations. The magnitudes of most of the associations were similar between
      the 2 dietary patterns, but some differences were observed between scores.
      Dietary patterns were not associated with blood pressure, coronary artery
      calcification, internal carotid intima-media thickness, or the ankle brachial
      index. CONCLUSIONS: Many food groups contribute to the characterization of
      relations with a variety of CVD risk markers, although only 6 food groups
      contribute much of the information in MESA.

PMID- 18614742
TI  - Markers of dietary fat quality and fatty acid desaturation as predictors of total
      and cardiovascular mortality: a population-based prospective study.
AB  - BACKGROUND: Desaturase indexes, as markers of endogenous fatty acid desaturation,
      and a characteristic serum fatty acid (FA) composition are related to
      cardiovascular and metabolic diseases, but the relation to mortality is poorly
      investigated. OBJECTIVE: The objective was to evaluate the relation between
      dietary fat biomarkers, desaturase indexes, and mortality. DESIGN: In this
      community-based prospective sample, 50-y-old men were followed for a maximum of
      33.7 y. Cox proportional hazard analysis was conducted to investigate desaturase
      indexes (stearoyl-CoA-desaturase and Delta(6)- and Delta(5)-desaturase) and the
      relation of individual serum esterified fatty acids (FAs) in relation to total
      and cardiovascular mortality in the total study sample (n = 2009) and in a
      healthy subsample (n = 1885). Desaturase indexes were estimated as product-to
      precursor FA ratios. RESULTS: During follow-up, 1012 men in the total sample died
      and 931 men in the healthy subsample died. Desaturase indexes predicted both
      total and cardiovascular mortality. The relations were independent of smoking
      status, physical activity, BMI, total cholesterol, and hypertension. The adjusted
      and standardized (per SD) hazard ratios (HRs) and 95% CIs for cardiovascular
      mortality were 1.15 (1.04, 1.27) for stearoyl-CoA-desaturase, 1.12 (1.0, 1.24)
      for Delta(6)-desaturase, and 0.88 (0.80, 0.98) for Delta(5)-desaturase,
      respectively. The proportion of serum linoleic acid was inversely related,
      whereas serum FAs associated with saturated fat intake (palmitic, palmitoleic,
      and dihomo-gamma-linolenic acids) were directly related to total and
      cardiovascular mortality. CONCLUSIONS: Altered endogenous FA desaturation might
      contribute to mortality risk because we observed independent associations between
      desaturase activity indexes and mortality. The proportion of linoleic acid was
      inversely related, and FAs reflecting saturated fat intake were directly related
      to mortality.

PMID- 18614743
TI  - Phylloquinone intake, insulin sensitivity, and glycemic status in men and women.
AB  - BACKGROUND: Limited evidence suggests that vitamin K may have a beneficial role
      in glucose homeostasis. No observational data exist on the associations between
      vitamin K intake and insulin sensitivity. OBJECTIVE: We aimed to examine
      associations between vitamin K intake and measures of insulin sensitivity and
      glycemic status in men and women aged 26-81 y. DESIGN: We assessed the cross
      sectional associations of self-reported phylloquinone (vitamin K(1)) intake with
      insulin sensitivity and glycemic status in the Framingham Offspring Cohort.
      Dietary and supplemental phylloquinone intakes were assessed by using a food
      frequency questionnaire. Insulin sensitivity was measured by fasting and 2-h post
      oral-glucose-tolerance test (OGTT) insulin, the homeostasis model assessment of
      insulin resistance (HOMA-IR), and the insulin sensitivity index (ISI(0,120)).
      Glycemic status was assessed by fasting and 2-h post-OGTT glucose and glycated
      hemoglobin (HbA(1c)). RESULTS: Higher phylloquinone intake was associated with
      greater insulin sensitivity and glycemic status, as measured by 2-h post-OGTT
      insulin and glucose and ISI(0,120), after adjustment for age, sex, waist
      circumference, lifestyle characteristics, and diet quality [2-h post-OGTT
      insulin: lowest and highest quintile, 81.0 and 72.7 microU/mL, respectively (P
      for trend = 0.003); 2-h post-OGTT glucose: 106.3 and 101.9 mg/dL, respectively (P
      for trend = 0.009); ISI(0,120): 26.3 and 27.3 mg L(2)/mmol mU min (P for trend =
      0.009)]. Phylloquinone intake was not associated with fasting insulin and glucose
      concentrations, HOMA-IR, or HbA(1c). CONCLUSION: Our findings support a potential
      beneficial role for phylloquinone in glucose homeostasis in men and women.

PMID- 18614744
TI  - Blood concentrations of individual long-chain n-3 fatty acids and risk of
      nonfatal myocardial infarction.
AB  - BACKGROUND: Whereas dietary intake of long-chain n-3 fatty acids has been
      associated with risk of nonfatal myocardial infarction (MI), few studies have
      examined the relation for blood concentrations. OBJECTIVE: We aimed to
      investigate the effect of long-chain n-3 fatty acids in blood on the risk of
      nonfatal MI. DESIGN: Baseline blood samples were collected from 32 826
      participants of the Nurses' Health Study in 1989-1990, among whom 146 incident
      cases of nonfatal MI were ascertained during 6 y of follow-up and matched with
      288 controls. RESULTS: After multivariate adjustment, the relative risks (95% CI)
      comparing the highest with the lowest quartiles in plasma were 0.23 (0.09, 0.55;
      P for trend = 0.001) for eicosapentaenoic acid (EPA), 0.40 (0.20, 0.82; P for
      trend = 0.004) for docosapentaenoic acid (DPA), and 0.46 (0.18, 1.16; P for trend
      = 0.07) for docosahexaenoic acid (DHA). The associations for these fatty acids in
      erythrocytes were generally weaker and nonsignificant. In contrast to EPA and
      DHA, blood concentrations of DPA were not correlated with dietary consumption of
      n-3 fatty acids. Higher plasma concentrations of EPA, DPA, and DHA were
      associated with higher plasma concentrations of HDL cholesterol and lower
      concentrations of triacylglycerol and inflammatory markers. CONCLUSIONS: Higher
      plasma concentrations of EPA and DPA are associated with a lower risk of nonfatal
      MI among women. These findings may partly reflect dietary consumption but,
      particularly for DPA, may indicate important risk differences based on metabolism
      of long-chain n-3 fatty acids.

PMID- 18614745
TI  - Tea consumption and cognitive impairment and decline in older Chinese adults.
AB  - BACKGROUND: Laboratory research suggests that tea has potential neurocognitive
      protective effects, but this is not established in humans. OBJECTIVE: We aimed to
      examine the relation between tea intake and cognitive impairment and decline.
      DESIGN: Among community-living Chinese adults aged > or = 55 y in the Singapore
      Longitudinal Ageing Studies cohort, we measured tea consumption at baseline and
      administered the Mini-Mental State Examination (MMSE) at baseline and 1-2 y
      later. Cognitive impairment was defined as an MMSE score < or = 23 and cognitive
      decline as a drop in MMSE score of > or = 1 point. We performed cross-sectional
      analysis of baseline data from 2501 participants and longitudinal analysis of
      data from 1438 cognitively intact participants. Odds ratios (ORs) of association
      were calculated in logistic regression models that adjusted for potential
      confounders. RESULTS: Total tea intake was significantly associated with a lower
      prevalence of cognitive impairment, independent of other risk factors. Compared
      with the ORs for rare or no tea intake, the ORs for low, medium, and high levels
      of tea intake were 0.56 (95% CI: 0.40, 0.78), 0.45 (95% CI: 0.27, 0.72), and 0.37
      (95% CI: 0.14, 0.98), respectively (P for trend < 0.001). For cognitive decline,
      the corresponding ORs were 0.74 (95% CI: 0.54, 1.00), 0.78 (95% CI: 0.55, 1.11),
      and 0.57 (95% CI: 0.32, 1.03), respectively (P for trend = 0.042). These effects
      were most evident for black (fermented) and oolong (semi-fermented) teas, the
      predominant types consumed by this population. In contrast, no association
      between coffee intake and cognitive status was found. CONCLUSION: Regular tea
      consumption was associated with lower risks of cognitive impairment and decline.

PMID- 18614746
TI  - Prevalence and effects of gene-gene and gene-nutrient interactions on serum
      folate and serum total homocysteine concentrations in the United States: findings
      from the third National Health and Nutrition Examination Survey DNA Bank.
AB  - BACKGROUND: Abnormalities of folate and homocysteine metabolism are associated
      with a number of pediatric and adult disorders. Folate intake and genetic
      polymorphisms encoding folate-metabolizing enzymes influence blood folate and
      homocysteine concentrations, but the effects and interactions of these factors
      have not been studied on a population-wide basis. OBJECTIVE: The objective was to
      assess the prevalence of these genetic polymorphisms and their relation to serum
      folate and homocysteine concentrations. DESIGN: DNA samples from 6793
      participants in the third National Health and Nutrition Examination Survey
      (NHANES III) during 1991-1994 were genotyped for polymorphisms of genes coding
      for folate pathway enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-
      >T and 1298A-->C, methionine synthase reductase (MTRR) 66A-->G, and cystathionine
      beta-synthase 844ins68. The influence of these genetic variants on serum folate
      and homocysteine concentrations was analyzed by age, sex, and folate intake in 3
      race-ethnicity groups. RESULTS: For all race-ethnicity groups, serum folate and
      homocysteine concentrations were significantly related to the MTHFR 677C-->T
      genotype but not to the other polymorphisms. Persons with the MTHFR 677 TT
      genotype had a 22.1% (95% CI: 14.6%, 28.9%) lower serum folate and a 25.7% (95%
      CI: 18.6%, 33.2%) higher homocysteine concentration than did persons with the CC
      genotype. Moderate daily folic acid intake (mean: 150 microg/d; 95% CI: 138, 162)
      significantly reduced the difference in mean homocysteine concentrations between
      those with the MTHFR 677 CC and TT genotypes. We found a significant interaction
      between MTHFR 677C-->T and MTRR 66A-->G on serum homocysteine concentrations
      among non-Hispanic whites. CONCLUSIONS: The MTHFR 677C-->T polymorphism was
      associated with significant differences in serum folate and homocysteine
      concentrations in the US population before folic acid fortification. The effect
      of MTHFR 677C-->T on homocysteine concentrations was reduced by moderate daily
      folic acid intake.

PMID- 18614747
TI  - Dietary betaine and inflammation.

PMID- 18614748
TI  - Triglyceride concentrations and endotoxemia.

PMID- 18614749
TI  - Tigecycline for the treatment of Acinetobacter infections: a case series.
AB  - BACKGROUND: Acinetobacter infections resistant to multiple classes of antibiotics
      have become prevalent in many institutions. Tigecycline has in vitro activity
      against Acinetobacter spp. and has been suggested as a therapeutic option in
      these infections. OBJECTIVE: To describe the clinical and microbiologic outcomes
      of patients who received tigecycline for the treatment of infections caused by
      Acinetobacter spp. at our institution. METHODS: A retrospective review was
      conducted of the medical records of 29 sequential patients who received
      tigecycline for treatment of Acinetobacter infections. The outcomes assessed for
      efficacy were clinical improvement or cure and microbiologic cure in evaluable
      patients. RESULTS: Patients received tigecycline a median of 30 days into
      hospitalization for a median of 11 days. Common indications were pneumonia (15
      pts.), bacteremia (6), and urinary tract infection (3). Positive clinical
      outcomes (clinical cure or improvement) were seen in 8 (28%) of 29 patients. Of
      the 25 microbiologically evaluable patients, 11 (44%) had resolution of their
      cultures. Eleven patients had susceptibility testing performed, and the median
      minimum inhibitory concentration was 4 microg/mL (range 3-8). CONCLUSIONS: In
      this case series, most patients did not have clinically or microbiologically
      favorable outcomes with tigecycline therapy. No patient had an isolate that was
      fully susceptible to tigecycline. Data from more studies are needed before
      tigecycline can be recommended for the treatment of Acinetobacter infections.

PMID- 18614750
TI  - Physical and chemical stability of esomeprazole sodium solutions.
AB  - BACKGROUND: Esomeprazole sodium (Nexium IV, AstraZeneca) is the S-isomer of
      omeprazole and acts as a proton pump inhibitor gastric antisecretory agent
      indicated for the short-term treatment of gastroesophageal reflux disease in
      patients with a history of erosive esophagitis. Currently, there is no
      information on the long-term stability of esomeprazole sodium in infusion
      solutions beyond 12 hours. OBJECTIVE: To evaluate the stability of esomeprazole
      sodium in 5% dextrose, 0.9% sodium chloride, and lactated Ringer's injection, at
      2 concentrations, at room temperature and when refrigerated. METHODS: Triplicate
      samples of esomeprazole 0.4 and 0.8 mg/mL as the sodium salt were prepared in the
      solutions required. Stability evaluations were performed initially, over 2 days
      stored at 23 degrees C, and over 5 days stored at 4 degrees C. Physical stability
      was assessed using turbidimetric and particulate measurement, as well as visual
      observation. Chemical stability was evaluated by stability-indicating high
      performance liquid chromatography. RESULTS: The samples in all 3 infusion
      solutions were physically stable throughout the study. None of the samples had
      evidence of visible haze or particulates. Most samples developed a slight yellow
      discoloration within 24 hours, but this discoloration was not accompanied by an
      excessive loss of drug content. The esomeprazole sodium samples in all 3 infusion
      solutions exhibited less than 7% loss over 2 days at 23 degrees C and over 5 days
      at 4 degrees C. CONCLUSIONS: Esomeprazole 0.4 and 0.8 mg/mL as the sodium salt in
      the infusion solutions tested is chemically and physically stable for at least 2
      days at room temperature and 5 days under refrigeration.

PMID- 18614751
TI  - The Medium-Chain Dehydrogenase/reductase Engineering Database: a systematic
      analysis of a diverse protein family to understand sequence-structure-function
      relationship.
AB  - The Medium-Chain Dehydrogenase/Reductase Engineering Database (MDRED,
      http://www.mdred.uni-stuttgart.de) has been established to serve as an analysis
      tool for a systematic investigation of sequence-structure-function relationships.
      It includes sequence and structure information of 2684 and 42 medium-chain
      dehydrogenases/reductases (MDRs), respectively. Although MDRs are very diverse in
      sequence, they have a conserved tertiary structure. MDRs are assigned to 199
      homologous families and 29 superfamilies. For each family, annotated multiple
      sequence alignments are provided, and functionally relevant residues are
      annotated. Twenty-five superfamilies were classified as zinc-containing MDRs,
      four as non-zinc-containing MDRs. For the zinc-containing MDRs, three subclasses
      were identified by systematic analysis of a variable loop region, the quaternary
      structure determining loop (QSDL): the class of short, medium, and long QSDL,
      which include 11, 3, and 5 superfamilies, respectively. The length of the QSDL is
      predictive for tetramer (short QSDL) and dimer (long QSDL) formation. The class
      of medium QSDL includes both tetrameric and dimeric MDRs. The shape of the
      substrate-binding site is highly conserved in all zinc-containing MDRs with the
      exception of two variable regions, the substrate recognition sites (SRS): two
      residues located on the QSDL (SRS1) and, for the class of long QSDL, one residue
      located in the catalytic domain (SRS2). The MDRED is the first online-accessible
      resource of MDRs that integrates information on sequence, structure, and
      function. Annotation of functionally relevant residues assist the understanding
      of sequence-structure-function relationships. Thus, the MDRED serves as a
      valuable tool to identify potential hotspots for engineering properties such as
      substrate specificity.

PMID- 18614752
TI  - Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'
      seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes.
AB  - Massively parallel sequencing of millions of < 30-nt RNAs expressed in mouse
      ovary, embryonic pancreas (E14.5), and insulin-secreting beta-cells (betaTC-3)
      reveals that approximately 50% of the mature miRNAs representing mostly the mmu
      let-7 family display internal insertion/deletions and substitutions when compared
      to precursor miRNA and the mouse genome reference sequences. Approximately, 12%
      20% of species associated with mmu-let-7 populations exhibit sequence
      discrepancies that are dramatically reduced in nucleotides 3-7 (5'-seed) and 10
      15 (cleavage and anchor sites). This observation is inconsistent with sequencing
      error and leads us to propose that the changes arise predominantly from post
      transcriptional RNA-editing activity operating on miRNA:target mRNA complexes.
      Internal nucleotide modifications are most enriched at the ninth nucleotide
      position. A common ninth base edit of U-to-G results in a significant increase in
      stability of down-regulated let-7a targets in inhibin-deficient mice (Inha-/-).
      An excess of U-insertions (14.8%) over U-deletions (1.5%) and the presence of
      cleaved intermediates suggest that a mammalian TUTase (terminal uridylyl
      transferase) mediated dUTP-dependent U-insertion/U-deletion cycle may be a
      possible mechanism. We speculate that mRNA target site-directed editing of mmu
      let-7a duplex-bulges stabilizes "loose" miRNA:mRNA target associations and
      functions to expand the target repertoire and/or enhance mRNA decay over
      translational repression. Our results also demonstrate that the systematic study
      of sequence variation within specific RNA classes in a given cell type from
      millions of sequences generated by next-generation sequencing (NGS) technologies
      ("intranomics") can be used broadly to infer functional constraints on specific
      parts of completely uncharacterized RNAs.

PMID- 18614754
TI  - The representation of amplitude modulations in the mammalian auditory midbrain.
AB  - Temporal modulations in stimulus amplitude are essential for recognizing and
      categorizing behaviorally relevant acoustic signals such as speech. Despite this
      behavioral importance, it remains unclear how amplitude modulations (AMs) are
      represented in the responses of neurons at higher levels of the auditory system.
      Studies using stimuli with sinusoidal amplitude modulations (SAMs) have shown
      that the responses of many neurons are strongly tuned to modulation frequency,
      leading to the hypothesis that AMs are represented by their periodicity in the
      auditory midbrain. However, AMs in general are defined not only by their
      modulation frequency, but also by a number of other parameters (duration, duty
      cycle, etc.), which covary with modulation frequency in SAM stimuli. Thus the
      relationship between modulation frequency and neural responses as characterized
      with SAM stimuli alone is ambiguous. In this study, we characterize the
      representation of AMs in the gerbil inferior colliculus by analyzing neural
      responses to a series of pulse trains in which duration and interpulse interval
      are systematically varied to quantify the importance of duration, interpulse
      interval, duty cycle, and modulation frequency independently. We find that,
      although modulation frequency is indeed an important parameter for some neurons,
      the responses of many neurons are also strongly influenced by other AM
      parameters, typically duration and duty cycle. These results suggest that AMs are
      represented in the auditory midbrain not only by their periodicity, but by a
      complex combination of several important parameters.

PMID- 18614753
TI  - Behavioral states, network states, and sensory response variability.
AB  - We review data demonstrating that single-neuron sensory responses change with the
      states of the neural networks (indexed in terms of spectral properties of local
      field potentials) in which those neurons are embedded. We start with broad
      network changes--different levels of anesthesia and sleep--and then move to
      studies demonstrating that the sensory response plasticity associated with
      attention and experience can also be conceptualized as functions of network state
      changes. This leads naturally to the recent data that can be interpreted to
      suggest that even brief experience can change sensory responses via changes in
      network states and that trial-to-trial variability in sensory responses is a
      nonrandom function of network fluctuations, as well. We suggest that the CNS may
      have evolved specifically to deal with stimulus variability and that the coupling
      with network states may be central to sensory processing.

PMID- 18614755
TI  - Locomotor and reflex adaptation after partial denervation of ankle extensors in
      chronic spinal cats.
AB  - This work investigates the capacity of the spinal cord to generate locomotion
      after a complete spinal section and its ability to adapt its locomotor pattern
      after a peripheral nerve lesion. To study this intrinsic adaptive capacity, the
      left lateral gastrocnemius-soleus (LGS) nerve was sectioned in three cats that
      expressed a stable locomotion following a complete spinal transection. The
      electromyograph (EMG) of multiple hindlimb muscles and reflexes, evoked by
      stimulating the left tibial (Tib) nerve at the ankle, were recorded before and
      after denervation during treadmill locomotion. Following denervation, the mean
      amplitude of EMG bursts of multiple hindlimb muscles increased during locomotion,
      similar to what is found after an identical denervation in otherwise intact cats.
      Reflex changes were noted in ipsilateral flexors, such as semitendinosus and
      tibialis anterior, but not in the ipsilateral knee extensor vastus lateralis
      following denervation. The present results demonstrate that the spinal cord
      possesses the circuitry necessary to mediate increased EMG activity in multiple
      hindlimb muscles and also to produce changes in reflex pathways after a muscle
      denervation. The similarity of changes following LGS denervation in cats with an
      intact and transected spinal cord suggests that spinal mechanisms play a major
      role in the locomotor adaptation.

PMID- 18614756
TI  - Ethanol effects on dopaminergic ventral tegmental area neurons during block of
      Ih: involvement of barium-sensitive potassium currents.
AB  - The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) are
      important for the rewarding and reinforcing properties of drugs of abuse,
      including ethanol. Ethanol increases the firing frequency of DA VTA neurons from
      rats and mice. Because of a recent report on block of ethanol excitation in mouse
      DA VTA neurons with ZD7288, a selective blocker of the hyperpolarization
      activated cationic current Ih, we examined the effect of ZD7288 on ethanol
      excitation in DA VTA neurons from C57Bl/6J and DBA/2J mice and Fisher 344 rats.
      Ethanol (80 mM) caused only increases in firing rate in mouse DA VTA neurons in
      the absence of ZD7288, but in the presence of ZD7288 (30 microM), ethanol
      produced a more transient excitation followed by a decrease of firing. This same
      biphasic phenomenon was observed in DA VTA neurons from rats in the presence of
      ZD7288 only at very high ethanol concentrations (160-240 mM) but not at lower
      pharmacologically relevant concentrations. The longer latency ethanol-induced
      inhibition was not observed in DA VTA neurons from mice or rats in the presence
      of barium (100 microM), which blocks G protein-linked potassium channels (GIRKs)
      and other inwardly rectifying potassium channels. Ethanol may have a direct
      effect to increase an inhibitory potassium conductance, but this effect of
      ethanol can only decrease the firing rate if Ih is blocked.

PMID- 18614757
TI  - Detecting neural-state transitions using hidden Markov models for motor cortical
      prostheses.
AB  - Neural prosthetic interfaces use neural activity related to the planning and
      perimovement epochs of arm reaching to afford brain-directed control of external
      devices. Previous research has primarily centered on accurately decoding movement
      intention from either plan or perimovement activity, but has assumed that
      temporal boundaries between these epochs are known to the decoding system. In
      this work, we develop a technique to automatically differentiate between
      baseline, plan, and perimovement epochs of neural activity. Specifically, we use
      a generative model of neural activity to capture how neural activity varies
      between these three epochs. Our approach is based on a hidden Markov model (HMM),
      in which the latent variable (state) corresponds to the epoch of neural activity,
      coupled with a state-dependent Poisson firing model. Using an HMM, we demonstrate
      that the time of transition from baseline to plan epochs, a transition in neural
      activity that is not accompanied by any external behavior changes, can be
      detected using a threshold on the a posteriori HMM state probabilities. Following
      detection of the plan epoch, we show that the intended target of a center-out
      movement can be detected about as accurately as that by a maximum-likelihood
      estimator using a window of known plan activity. In addition, we demonstrate that
      our HMM can detect transitions in neural activity corresponding to targets not
      found in training data. Thus the HMM technique for automatically detecting
      transitions between epochs of neural activity enables prosthetic interfaces that
      can operate autonomously.

PMID- 18614758
TI  - Smooth pursuit eye movements to isoluminant targets.
AB  - At slow speeds, chromatic isoluminant stimuli are perceived to move much slower
      than comparable luminance stimuli. We investigated whether smooth pursuit eye
      movements to isoluminant stimuli show an analogous slowing. Beside pursuit speed
      and latency, we studied speed judgments to the same stimuli during fixation and
      pursuit. Stimuli were either large sine wave gratings or small Gaussians blobs
      moving horizontally at speeds between 1 and 11 degrees /s. Targets were defined
      by luminance contrast or color. Confirming prior studies, we found that speed
      judgments of isoluminant stimuli during fixation showed a substantial slowing
      when compared with luminance stimuli. A similarly strong and significant effect
      of isoluminance was found for pursuit initiation: compared with luminance targets
      of matched contrasts, latencies of pursuit initiation were delayed by 50 ms at
      all speeds and eye accelerations were reduced for isoluminant targets. A small
      difference was found between steady-state eye velocities of luminance and
      isoluminant targets. For comparison, we measured latencies of saccades to
      luminance and isoluminant stimuli under similar conditions, but the effect of
      isoluminance was only found for pursuit. Parallel psychophysical experiments
      revealed that different from speed judgments of moving isoluminant stimuli made
      during fixation, judgments during pursuit are veridical for the same stimuli at
      all speeds. Therefore information about target speed seems to be available for
      pursuit eye movements and speed judgments during pursuit but is degraded for
      perceptual speed judgments during fixation and for pursuit initiation.

PMID- 18614759
TI  - Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic
      endothelium reveals endothelial-specific molecule-1 as a novel mediator of
      lymphangiogenesis.
AB  - Lymphatic vessel growth and activation, mediated by vascular endothelial growth
      factor (VEGF)-C and/or VEGF-A, have important roles in metastasis and in chronic
      inflammation. We aimed to comprehensively identify downstream molecular targets
      induced by VEGF-A or VEGF-C in lymphatic endothelium by analyzing the time-series
      transcriptional profile of treated human dermal lymphatic endothelial cells
      (LECs). We identified a number of genes, many not previously known to be involved
      in lymphangiogenesis, that were characterized either as early response genes,
      transiently induced genes, or progressively induced genes. Endothelial-specific
      molecule-1 (ESM-1) was one of the genes that were most potently induced by both
      VEGF-A and VEGF-C. Whereas ESM-1 induction by VEGF-A was mainly dependent on
      activation of VEGFR-2, VEGF-C-mediated induction depended on the activity of both
      VEGFR-2 and VEGFR-3. Incubation of LECs with ESM-1 increased the stimulatory
      effects of both VEGF-A and VEGF-C on LEC proliferation and migration, whereas ESM
      1 alone had no effect. Importantly, VEGF-A (or VEGF-C) induction of LEC
      proliferation and migration were significantly inhibited by siRNA-mediated
      silencing of ESM-1 in vitro and in vivo. These studies reveal ESM-1 as a novel
      mediator of lymphangiogenesis and as a potential target for the inhibition of
      pathologic lymphatic vessel activation.

PMID- 18614760
TI  - TLR agonists regulate alloresponses and uncover a critical role for donor APCs in
      allogeneic bone marrow rejection.
AB  - Cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODNs) are synthetic
      ODNs with unmethylated DNA sequences that mimic viral and bacterial DNA and
      protect against infectious agents and tumor challenge. We show that CpG ODNs
      markedly accelerated graft-versus-host disease (GVHD) lethality by Toll-like
      receptor 9 (TLR9) ligation of host antigen-presenting cells (APCs), dependent
      upon host IFNgamma but independent of host IL-12, IL-6, or natural killer (NK)
      cells. Imaging studies showed significantly more green fluorescent protein
      positive (GFP(+)) effector T cells in lymphoid and nonlymphoid organs. In
      engraftment studies, CpG ODNs promoted allogeneic donor bone marrow (BM)
      rejection independent of host IFNgamma, IL-12, or IL-6. During the course of
      these studies, we uncovered a previously unknown and critical role of donor BM
      APCs in modulating the rejection response. CpG ODNs promoted BM rejection by
      ligation of donor BM, but not host, TLR9. CpG ODNs did not impair engraftment of
      TLR9(-/-) BM unless wild-type myeloid (CD11b(+)) but not B-lineage (CD19(+)) BM
      cells were added to the donor inoculum. The importance of donor BM APCs in
      modulating the strength of the host antidonor rejection response was underscored
      by the finding that B7-1/B7-2(-/-) BM was less likely than wild-type BM to be
      rejected. Collectively, these data offer new insight into the mechanism of
      alloresponses regulating GVHD and BM rejection.

PMID- 18614761
TI  - High-density lipoprotein cholesterol and venous thromboembolism in the
      Longitudinal Investigation of Thromboembolism Etiology (LITE).
AB  - We determined prospectively the risk of venous thromboembolism (VTE) in relation
      to baseline high-density lipoprotein cholesterol (HDL-c) in 19 049 participants
      of the Longitudinal Investigation of Thromboembolism Etiology (LITE), which was
      composed of 14 490 participants of the Atherosclerosis Risk in Communities (ARIC)
      study and 4559 participants of the Cardiovascular Health Study (CHS). In
      addition, we determined the risk of VTE in relation to baseline subfractions of
      HDL (HDL(2) and HDL(3)) and apolipoprotein A-I (apoA-I) in 14 488 participants of
      the ARIC study. Age-adjusted incidence rates of VTE by HDL-c quartile ranged from
      1.64 to 1.91 per 1000 person-years in men and 1.40 to 1.94 per 1000 person-years
      in women; however, there was no apparent trend of VTE incidence across HDL-c
      quartiles for either sex. The multivariate adjusted hazard ratios of VTE by HDL-c
      quartiles (with quartile 4 as the reference) were nonsignificant for both sexes
      and ranged between 0.91 and 0.99 for men and 0.78 and 1.22 for women. Results did
      not differ in separate evaluations of idiopathic and secondary VTE. In the ARIC
      study, there was no trend of VTE hazard ratios across quartiles of HDL(2),
      HDL(3), or apoA-I. Low HDL-c does not appear to be an important VTE risk factor.

PMID- 18614763
TI  - Prokineticin 2 influences subfornical organ neurons through regulation of MAP
      kinase and the modulation of sodium channels.
AB  - Prokineticin 2 (PK2) is a neuropeptide that acts as a signaling molecule
      regulating circadian rhythms in mammals. We have previously reported PK2 actions
      on subfornical organ (SFO) neurons, identifying this circumventricular organ as a
      target at which PK2 acts to influence autonomic control (Cottrell GT, and
      Ferguson AV. J. Neurosci. 24: 2375-2379, 2004). In this study, we have examined
      the cellular mechanisms by which PK2 increases the excitability of SFO neurons.
      Whole cell patch recordings from dissociated rat SFO neurons demonstrated that
      the mitogen-activated protein (MAP) kinase inhibitor PD-98059 prevented PK2
      induced depolarization and decreases in delayed rectifier K(+) current. PK2 also
      increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in 39% of dissociated
      SFO neurons (mean increase = 20.8 +/- 5.5%), effects that were maintained in the
      presence of thapsigargin but abolished by both nifedipine, or the absence of
      extracellular Ca(2+), suggesting that PK2-induced [Ca(2+)](i) transients resulted
      from Ca(2+) entry through voltage-gated Ca(2+) channels. Voltage-clamp recordings
      showed that PK2 was without effects on Ca(2+) currents evoked by voltage ramps,
      suggesting that PK2-induced Ca(2+) influx was secondary to PK2-induced increases
      in action potential frequency, an hypothesis supported by data showing that
      tetrodotoxin abolished effects of PK2 on [Ca(2+)](i). These observations
      suggested PK2 modulation of voltage-gated Na(+) currents, a possibility confirmed
      by voltage-clamp experiments showing that PK2 increased the amplitude of both
      transient and persistent Na(+) currents in 29% of SFO neurons (by 34 and 38%,
      respectively). These data indicate that PK2 influences SFO neurons through the
      activation of a MAP kinase cascade, which, in turn, modulates Na(+) and K(+)
      conductances.

PMID- 18614762
TI  - Interruption of the Ras/MEK/ERK signaling cascade enhances Chk1 inhibitor-induced
      DNA damage in vitro and in vivo in human multiple myeloma cells.
AB  - The role of the Ras/MEK/ERK pathway was examined in relation to DNA damage in
      human multiple myeloma (MM) cells exposed to Chk1 inhibitors in vitro and in
      vivo. Exposure of various MM cells to marginally toxic concentrations of the Chk1
      inhibitors UCN-01 or Chk1i modestly induced DNA damage, accompanied by Ras and
      ERK1/2 activation. Interruption of these events by pharmacologic (eg, the
      farnesyltransferase inhibitor R115777 or the MEK1/2 inhibitor PD184352) or
      genetic (eg, transfection with dominant-negative Ras or MEK1 shRNA) means induced
      pronounced DNA damage, reflected by increased gammaH2A.X expression/foci
      formation and by comet assay. Increased DNA damage preceded extensive apoptosis.
      Notably, similar phenomena were observed in primary CD138(+) MM cells. Enforced
      MEK1/2 activation by B-Raf transfection prevented R115777 but not PD184352 from
      inactivating ERK1/2 and promoting Chk1 inhibitor-induced gammaH2A.X expression.
      Finally, coadministration of R115777 diminished UCN-01-mediated ERK1/2 activation
      and markedly potentiated gammaH2A.X expression in a MM xenograft model,
      associated with a striking increase in tumor cell apoptosis and growth
      suppression. Such findings suggest that Ras/MEK/ERK activation opposes whereas
      its inhibition dramatically promotes Chk1 antagonist-mediated DNA damage.
      Together, these findings identify a novel mechanism by which agents targeting the
      Ras/MEK/ERK pathway potentiate Chk1 inhibitor lethality in MM.

PMID- 18614764
TI  - Astrocyte responses to injury: VEGF simultaneously modulates cell death and
      proliferation.
AB  - Hypoxia is linked to changes in blood-brain barrier (BBB) permeability, and loss
      of BBB integrity is characteristic of many pathological brain diseases including
      stroke. In particular, astrocytes play a central role in brain homeostasis and
      BBB function. We investigated how hypoxia affects astrocyte survival and assessed
      whether VEGF release through hypoxia-inducible factor-1alpha (HIF-1alpha)
      induction plays a role in tolerance of these cells to insult. Thus primary
      astrocytes were subjected to normoxic (21% O(2)), hypoxic (1% O(2)), or near
      anoxic (<0.1% O(2)) conditions in the presence or absence of glucose. Cell death
      was significantly initiated after combined oxygen glucose deprivation, and,
      surprisingly, astrocyte proliferation increased concomitantly. Near anoxic, but
      not hypoxic, conditions stabilized HIF-1alpha protein and provoked DNA binding
      activity, whereas oxygen and glucose deprivation accelerated HIF-1alpha
      accumulation. Unexpectedly, Hif-1alpha knockdown studies showed that elevated
      VEGF levels following increased insult was only partially due to HIF-1alpha
      induction, suggesting alternative mechanisms of VEGF regulation. Notably,
      endogenous VEGF signaling during insult was essential for cell fate since VEGF
      inhibition appreciably augmented cell death and reduced proliferation. These data
      suggest Hif-1 only partially contributes to VEGF-mediated astrocyte responses
      during chronic injury (as occurs in clinical hypoxic/ischemic insults) that may
      ultimately be responsible for disrupting BBB integrity.

PMID- 18614765
TI  - Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in
      renal arterioles.
AB  - Vascular conducted responses are believed to play a central role in controlling
      the microcirculatory blood flow. The responses most likely spread through gap
      junctions in the vascular wall. At present, four different connexins (Cx) have
      been detected in the renal vasculature, but their role in transmission of
      conducted vasoconstrictor signals in the preglomerular arterioles is unknown.
      Connexin mimetic peptides were previously reported to target and inhibit specific
      connexins. We, therefore, investigated whether conducted vasoconstriction in
      isolated renal arterioles could be blocked by the use of mimetic peptides
      directed against one or more connexins. Preglomerular resistance vessels were
      microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The
      vessels were stimulated locally by applying electrical current through a
      micropipette, and the conducted calcium response was measured 500 mum from the
      site of stimulation. Application of connexin mimetic peptides directed against
      Cx40, 37/43, 45, or a cocktail with equimolar amounts of each, did not inhibit
      the propagated response, whereas the nonselective gap junction uncoupler
      carbenoxolone completely abolished the propagated response. However, the connexin
      mimetic peptides were able to reduce dye coupling between rat aorta endothelial
      cells shown to express primarily Cx40. In conclusion, we did not observe any
      attenuating effects on conducted calcium responses in isolated rat interlobular
      arteries when exposed to connexin mimetic peptides directed against Cx40, 37/43,
      or 45. Further studies are needed to determine whether conducted vasoconstriction
      is mediated via previously undescribed pathways.

PMID- 18614766
TI  - Dietary sodium manipulation during critical periods in development sensitize
      adult offspring to amphetamines.
AB  - This study examined critical periods in development to determine when offspring
      were most susceptible to dietary sodium manipulation leading to amphetamine
      sensitization. Wistar dams (n = 6-8/group) were fed chow containing low (0.12%
      NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal
      or early postnatal period (birth to 5 wk). Offspring were fed normal chow
      thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid
      intake, salt preference, response to amphetamine, open field behavior, plasma
      adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal
      gland weight were measured. BW was similar for all offspring. Offspring from the
      prenatal and postnatal HN group had increased BP, NaCl intake, and salt
      preference and decreased water intake relative to NN offspring. Prenatal HN
      offspring had greater BP than postnatal HN offspring. In response to amphetamine,
      both prenatal and postnatal LN and HN offspring had increased locomotor behavior
      compared with NN offspring. In a novel open field environment, locomotion was
      also increased in prenatal and postnatal LN and HN offspring compared with NN
      offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland
      weight measurement were greater in LN and HN offspring compared with NN
      offspring. These results indicate that early life experience with low- and high
      sodium diets, during the prenatal or early postnatal period, is a stress that
      produces long-term changes in responsiveness to amphetamines and to subsequent
      stressors.

PMID- 18614768
TI  - Absolute spike frequency predicts surgical outcome in TLE with unilateral
      hippocampal atrophy.
AB  - OBJECTIVE: To assess the prognostic implications of both the absolute spike
      frequency over the affected temporal lobe and the relative spike distribution
      between the two temporal lobes (i.e., uni- vs bitemporal spike distribution) for
      postoperative seizure control in a series of consecutive patients with medically
      refractory mesial temporal lobe epilepsy (MTLE) and MRI evidence of unilateral
      hippocampal atrophy (HA). METHODS: In this study we included 55 patients (26
      women; 29 men) with medically refractory MTLE and unilateral HA on high
      resolution MRI who underwent a comprehensive noninvasive presurgical evaluation
      including prolonged video-EEG monitoring. Patients were classified both according
      to absolute interictal spike frequency and to relative spike distribution between
      the two temporal lobes as follows: first, we distinguished between patients with
      frequent spikes (>/=60 spikes/hour over the affected temporal lobe) and patients
      with nonfrequent spikes (<60 spikes/hour over the affected temporal lobe).
      Second, we categorized patients in a unitemporal group (>/=90% of spikes over the
      affected temporal lobe) and a bitemporal group (<90% of spikes over the affected
      temporal lobe). In all patients first-time epilepsy surgery was performed with a
      minimum postoperative follow-up of 1 year. RESULTS: One year following surgery we
      found that only 4 of 14 patients (28.6%) in the frequent spikes group remained
      completely seizure free since surgery compared to 33 of 41 patients (80.5%) in
      the nonfrequent spikes group (p = 0.001). Relative spike distribution did not
      show any significant implication for postoperative outcome. CONCLUSIONS: This
      study identified absolute preoperative spike frequency as a strong predictor for
      surgical outcome, while relative spike distribution had no significant influence
      on postoperative seizure control.

PMID- 18614769
TI  - Active vitamin D and survival.

PMID- 18614767
TI  - Kv1.3 channels in postganglionic sympathetic neurons: expression, function, and
      modulation.
AB  - Kv1.3 channels are known to modulate many aspects of neuronal function. We tested
      the hypothesis that Kv1.3 modulates the function of postganglionic sympathetic
      neurons. RT-PCR, immunoblot, and immunohistochemical analyses indicated that
      Kv1.3 channels were expressed in these neurons. Immunohistochemical analyses
      indicated that Kv1.3 protein was localized to neuronal cell bodies, processes,
      and nerve fibers at sympathetic neurovascular junctions. Margatoxin (MgTX), a
      specific inhibitor of Kv1.3, was used to assess the function of the channel.
      Electrophysiological analyses indicated that MgTX significantly reduced outward
      currents [P < 0.05; n = 18 (control) and 15 (MgTX)], depolarized resting membrane
      potential, and decreased the latency to action potential firing [P < 0.05; n = 11
      (control) and 13 (MgTX)]. The primary physiological input to postganglionic
      sympathetic neurons is ACh, which activates nicotinic and muscarinic ACh
      receptors. MgTX modulated nicotinic ACh receptor agonist-induced norepinephrine
      release (P < 0.05; n >or= 6), and MgTX-sensitive current was suppressed upon
      activation of muscarinic ACh receptors with bethanechol (P < 0.05; n = 12). These
      data indicate that Kv1.3 affects the function of postganglionic sympathetic
      neurons, which suggests that Kv1.3 influences sympathetic control of
      cardiovascular function. Our data also indicate that modulation of Kv1.3 is
      likely to affect sympathetic control of cardiovascular function.

PMID- 18614770
TI  - Hemoglobin in the kidney: breaking with traditional dogma.

PMID- 18614771
TI  - Fenestrated glomerular capillaries are unique.

PMID- 18614772
TI  - Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome.
AB  - Classically, infants with mutations in NPHS1, which encodes nephrin, present with
      nephrotic syndrome within the first 3 mo of life (congenital nephrotic syndrome
      of the Finnish-type), and children with mutations in NPHS2, which encodes
      podocin, present later with steroid-resistant nephrotic syndrome. Recently,
      however, NPHS2 mutations have been identified in children with congenital
      nephrotic syndrome. Whether NPHS1 mutations similarly account for some cases of
      childhood steroid-resistant nephrotic syndrome is unknown. In this study, 160
      patients who belonged to 142 unrelated families and presented with nephrotic
      syndrome at least 3 mo after birth were screened for NPHS1 variants once
      mutations in NPHS2 had been excluded. Compound heterozygous NPHS1 mutations were
      identified in one familial case and nine sporadic cases. Mutations included
      protein-truncating nonsense and frameshift mutations, as well as splice-site and
      missense variants. Mutations were classified as "severe" or "mild" using
      prediction algorithms and functional assays. Most missense variants trafficked
      normally to the plasma membrane and maintained the ability to form nephrin
      homodimers and to heterodimerize with NEPH1, suggesting retained function. The
      presence of at least one "mild" mutation in these patients likely explains the
      later onset and milder course of disease. These results broaden the spectrum of
      renal disease related to nephrin mutations.

PMID- 18614773
TI  - Cost-effectiveness of frequent in-center hemodialysis.
AB  - Published evidence suggests that frequent hemodialysis (more than three times per
      week) for patients with ESRD may improve health-related quality of life and has
      the potential to increase longevity and reduce hospitalization and other
      complications. Here, a Monte Carlo simulation model was used to compare varying
      combinations of in-center hemodialysis frequency (three to six treatments per
      week) and session length (2 to 4.5 h per session) with regard to unadjusted and
      quality-adjusted life-years and total lifetime costs for a cohort of 200,000
      patients, representing the prevalent ESRD population. The incremental cost
      effectiveness ratio was calculated for the various regimens relative to a
      conventional hemodialysis regimen (three treatments per week, 3.5 h per session).
      Using conservative assumptions of the potential effects of more frequent
      hemodialysis on outcomes, most strategies achieved a cost-effectiveness ratio of
      <$125,000, although all had a cost-effectiveness ratio of >$75,000. The cost
      effectiveness ratio increased with the frequency of hemodialysis. More frequent
      in-center hemodialysis strategies could become cost-neutral if the cost per
      hemodialysis session could be reduced by 32 to 43%. No other change in model
      assumptions achieved cost neutrality. In conclusion, given the extraordinarily
      high costs of the ESRD program, the viability of more frequent hemodialysis
      strategies depends on significant improvements in the economic model underlying
      the delivery of hemodialysis.

PMID- 18614775
TI  - Associations of kidney function with cardiovascular medication use after
      myocardial infarction.
AB  - BACKGROUND AND OBJECTIVES: It is unknown whether adherence to recommended
      medications after myocardial infarction (MI) differs by kidney function. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective cohort study of
      older patients who were discharged after MI in two Eastern states between 1995
      and 2004. Patients were categorized as having ESRD, having chronic kidney disease
      (CKD), and being free from diagnosed CKD. Use of angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers (ACEI/ARB), beta blockers (BB), and
      statins was assessed within 30 d after discharge. Good adherence was defined as
      proportion of days covered >80% during the first year after discharge. RESULTS:
      Compared with patients with no CKD, patients with CKD had 22% lower adjusted use
      of ACEI/ARB but similar rates of BB and statin use. Patients with ESRD
      experienced 43% lower ACEI/ARB and 17% lower statin use. Only 64% (BB), 57%
      (statins), and 54% (ACEI/ARB) of patients had good 1-yr adherence. Adherence was
      similar between patients with CKD and with no CKD for all study drugs. Fewer
      patients with ESRD had good adherence to BB. CONCLUSIONS: With the exception of
      lower ACEI/ARB use in patients with CKD, we found no differences between patients
      with CKD and with no CKD in their use of and adherence to these cardiovascular
      medications after MI. Patients with ESRD experienced lower use of ACEI/ARB and
      statins and lower adherence to BB regimens. Postulated differences in medication
      use after MI across levels of kidney function are unlikely to explain the
      observed differences in long-term outcomes.

PMID- 18614774
TI  - Macrophage stimulating protein may promote tubular regeneration after acute
      injury.
AB  - Macrophage-stimulating protein (MSP) exerts proliferative and antiapoptotic
      effects, suggesting that it may play a role in tubular regeneration after acute
      kidney injury. In this study, elevated plasma levels of MSP were found both in
      critically ill patients with acute renal failure and in recipients of renal
      allografts during the first week after transplantation. In addition, MSP and its
      receptor, RON, were markedly upregulated in the regenerative phase after glycerol
      induced tubular injury in mice. In vitro, MSP stimulated tubular epithelial cell
      proliferation and conferred resistance to cisplatin-induced apoptosis by
      inhibiting caspase activation and modulating Fas, mitochondrial proteins, Akt,
      and extracellular signal-regulated kinase. MSP also enhanced migration,
      scattering, branching morphogenesis, tubulogenesis, and mesenchymal de
      differentiation of surviving tubular cells. In addition, MSP induced an embryonic
      phenotype characterized by Pax-2 expression. In conclusion, MSP is upregulated
      during the regeneration of injured tubular cells, and it exerts multiple biologic
      effects that may aid recovery from acute kidney injury.

PMID- 18614777
TI  - Guns and health.

PMID- 18614776
TI  - Pulmonary hypertension, right ventricular failure, and kidney: different from
      left ventricular failure?
AB  - In this article, the pathophysiology of left ventricular failure is reviewed. By
      contrast, the paucity of information about pulmonary arterial hypertension and
      right ventricular failure is acknowledged. The potential mechanisms whereby renal
      sodium and water retention in right ventricular failure secondary to pulmonary
      arterial hypertension can occur, despite normal left ventricular function, are
      discussed. With right ventricular failure as the primary cause of death in
      patients with pulmonary hypertension, more information about the mechanisms of
      renal sodium and water retention in these patients is direly needed.
      Specifically, studies to examine the activation of the neurohumoral axis at
      various stages of pulmonary arterial hypertension and right ventricular failure,
      including inhibition of mineralocorticoid and V2 vasopressin receptors, are
      indicated.

PMID- 18614778
TI  - Images in clinical medicine. Bifid uvula and aortic aneurysm.

PMID- 18614779
TI  - Shuffling toward parity--bringing mental health care under the umbrella.

PMID- 18614780
TI  - The (slowly) vanishing prescription pad.

PMID- 18614781
TI  - Noninvasive ventilation in acute cardiogenic pulmonary edema.
AB  - BACKGROUND: Noninvasive ventilation (continuous positive airway pressure [CPAP]
      or noninvasive intermittent positive-pressure ventilation [NIPPV]) appears to be
      of benefit in the immediate treatment of patients with acute cardiogenic
      pulmonary edema and may reduce mortality. We conducted a study to determine
      whether noninvasive ventilation reduces mortality and whether there are important
      differences in outcome associated with the method of treatment (CPAP or NIPPV).
      METHODS: In a multicenter, open, prospective, randomized, controlled trial,
      patients were assigned to standard oxygen therapy, CPAP (5 to 15 cm of water), or
      NIPPV (inspiratory pressure, 8 to 20 cm of water; expiratory pressure, 4 to 10 cm
      of water). The primary end point for the comparison between noninvasive
      ventilation and standard oxygen therapy was death within 7 days after the
      initiation of treatment, and the primary end point for the comparison between
      NIPPV and CPAP was death or intubation within 7 days. RESULTS: A total of 1069
      patients (mean [+/-SD] age, 77.7+/-9.7 years; female sex, 56.9%) were assigned to
      standard oxygen therapy (367 patients), CPAP (346 patients), or NIPPV (356
      patients). There was no significant difference in 7-day mortality between
      patients receiving standard oxygen therapy (9.8%) and those undergoing
      noninvasive ventilation (9.5%, P=0.87). There was no significant difference in
      the combined end point of death or intubation within 7 days between the two
      groups of patients undergoing noninvasive ventilation (11.7% for CPAP and 11.1%
      for NIPPV, P=0.81). As compared with standard oxygen therapy, noninvasive
      ventilation was associated with greater mean improvements at 1 hour after the
      beginning of treatment in patient-reported dyspnea (treatment difference, 0.7 on
      a visual-analogue scale ranging from 1 to 10; 95% confidence interval [CI], 0.2
      to 1.3; P=0.008), heart rate (treatment difference, 4 beats per minute; 95% CI, 1
      to 6; P=0.004), acidosis (treatment difference, pH 0.03; 95% CI, 0.02 to 0.04;
      P<0.001), and hypercapnia (treatment difference, 0.7 kPa [5.2 mm Hg]; 95% CI, 0.4
      to 0.9; P<0.001). There were no treatment-related adverse events. CONCLUSIONS: In
      patients with acute cardiogenic pulmonary edema, noninvasive ventilation induces
      a more rapid improvement in respiratory distress and metabolic disturbance than
      does standard oxygen therapy but has no effect on short-term mortality. (Current
      Controlled Trials number, ISRCTN07448447.)

PMID- 18614782
TI  - Familial myeloma.
AB  - We describe a family with five cases of multiple myeloma, three cases of
      monoclonal gammopathy of undetermined significance (MGUS), and five cases of
      prostate cancer in two generations. The putative progenitor had progeny with two
      female partners. The progeny had prostate cancer, multiple myeloma, and MGUS.

PMID- 18614784
TI  - Clinical practice. Initial management of epilepsy.

PMID- 18614783
TI  - Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia that is hereditary in a small subgroup
      of patients. In a family with 11 clinically affected members, we mapped an atrial
      fibrillation locus to chromosome 1p36-p35 and identified a heterozygous
      frameshift mutation in the gene encoding atrial natriuretic peptide. Circulating
      chimeric atrial natriuretic peptide (ANP) was detected in high concentration in
      subjects with the mutation, and shortened atrial action potentials were seen in
      an isolated heart model, creating a possible substrate for atrial fibrillation.
      This report implicates perturbation of the atrial natriuretic peptide-cyclic
      guanosine monophosphate (cGMP) pathway in cardiac electrical instability.

PMID- 18614785
TI  - Images in clinical medicine. Digital verrucae.

PMID- 18614786
TI  - Case records of the Massachusetts General Hospital. Case 21-2008. An 11-month-old
      boy with fever and pulmonary infiltrates.

PMID- 18614787
TI  - Wellness programs and lifestyle discrimination--the legal limits.

PMID- 18614788
TI  - Quality of life and satisfaction with outcome among prostate-cancer survivors.

PMID- 18614789
TI  - Coronary calcium and events in four ethnic groups.

PMID- 18614790
TI  - VEGF inhibition and renal thrombotic microangiopathy.

PMID- 18614791
TI  - Case 11-2008: Mental-status changes after liver transplantation.

PMID- 18614792
TI  - Shifts in health information.

PMID- 18614793
TI  - Duration of survival in patients with myeloma treated with thalidomide.

PMID- 18614794
TI  - Coordinated lipid transfer between the endoplasmic reticulum and the Golgi
      complex requires the VAP proteins and is essential for Golgi-mediated transport.
AB  - Lipid transport between intracellular organelles is mediated by vesicular and
      nonvesicular transport mechanisms and is critical for maintaining the identities
      of different cellular membranes. Nonvesicular lipid transport between the
      endoplasmic reticulum (ER) and the Golgi complex has been proposed to affect the
      lipid composition of the Golgi membranes. Here, we show that the integral ER
      membrane proteins VAP-A and VAP-B affect the structural and functional integrity
      of the Golgi complex. Depletion of VAPs by RNA interference reduces the levels of
      phosphatidylinositol-4-phosphate (PI4P), diacylglycerol, and sphingomyelin in the
      Golgi membranes, and it leads to substantial inhibition of Golgi-mediated
      transport events. These effects are coordinately mediated by the lipid
      transfer/binding proteins Nir2, oxysterol-binding protein (OSBP), and ceramide
      transfer protein (CERT), which interact with VAPs via their FFAT motif. The
      effect of VAPs on PI4P levels is mediated by the
      phosphatidylinositol/phosphatidylcholine transfer protein Nir2, which is required
      for Golgi targeting of OSBP and CERT and the subsequent production of
      diacylglycerol and sphingomyelin. We propose that Nir2, OSBP, and CERT function
      coordinately at the ER-Golgi membrane contact sites, thereby affecting the lipid
      composition of the Golgi membranes and consequently their structural and
      functional identities.

PMID- 18614795
TI  - The yeast Aac2 protein exists in physical association with the cytochrome bc1-COX
      supercomplex and the TIM23 machinery.
AB  - The ADP/ATP carrier (AAC) proteins play a central role in cellular metabolism as
      they facilitate the exchange of ADP and ATP across the mitochondrial inner
      membrane. We present evidence here that in yeast (Saccharomyces cerevisiae)
      mitochondria the abundant Aac2 isoform exists in physical association with the
      cytochrome c reductase (cytochrome bc(1))-cytochrome c oxidase (COX) supercomplex
      and its associated TIM23 machinery. Using a His-tagged Aac2 derivative and
      affinity purification studies, we also demonstrate here that the Aac2 isoform can
      be affinity-purified with other AAC proteins. Copurification of the Aac2 protein
      with the TIM23 machinery can occur independently of its association with the
      fully assembled cytochrome bc(1)-COX supercomplex. In the absence of the Aac2
      protein, the assembly of the cytochrome bc(1)-COX supercomplex is perturbed,
      whereby a decrease in the III(2)-IV(2) assembly state relative to the III(2)-IV
      form is observed. We propose that the association of the Aac2 protein with the
      cytochrome bc(1)-COX supercomplex is important for the function of the OXPHOS
      complexes and for the assembly of the COX complex. The physiological implications
      of the association of AAC with the cytochrome bc(1)-COX-TIM23 supercomplex are
      also discussed.

PMID- 18614796
TI  - Drosophila Sec16 mediates the biogenesis of tER sites upstream of Sar1 through an
      arginine-rich motif.
AB  - tER sites are specialized cup-shaped ER subdomains characterized by the focused
      budding of COPII vesicles. Sec16 has been proposed to be involved in the
      biogenesis of tER sites by binding to COPII coat components and clustering
      nascent-coated vesicles. Here, we show that Drosophila Sec16 (dSec16) acts
      instead as a tER scaffold upstream of the COPII machinery, including Sar1. We
      show that dSec16 is required for Sar1-GTP concentration to the tER sites where it
      recruits in turn the components of the COPII machinery to initiate coat assembly.
      Last, we show that the dSec16 domain required for its localization maps to an
      arginine-rich motif located in a nonconserved region. We propose a model in which
      dSec16 binds ER cups via its arginine-rich domain, interacts with Sar1-GTP that
      is generated on ER membrane by Sec12 and concentrates it in the ER cups where it
      initiates the formation of COPII vesicles, thus acting as a tER scaffold.

PMID- 18614797
TI  - Casein kinase 2 binds to the C terminus of Na+/H+ exchanger 3 (NHE3) and
      stimulates NHE3 basal activity by phosphorylating a separate site in NHE3.
AB  - Na(+)/H(+) exchanger 3 (NHE3) is the epithelial-brush border isoform responsible
      for most intestinal and renal Na(+) absorption. Its activity is both up- and down
      regulated under normal physiological conditions, and it is inhibited in most
      diarrheal diseases. NHE3 is phosphorylated under basal conditions and Ser/Thr
      phosphatase inhibitors stimulate basal exchange activity; however, the kinases
      involved are unknown. To identify kinases that regulate NHE3 under basal
      conditions, NHE3 was immunoprecipitated; LC-MS/MS of trypsinized NHE3 identified
      a novel phosphorylation site at S(719) of the C terminus, which was predicted to
      be a casein kinase 2 (CK2) phosphorylation site. This was confirmed by an in
      vitro kinase assay. The NHE3-S719A mutant but not NHE3-S719D had reduced NHE3
      activity due to less plasma membrane NHE3. This was due to reduced exocytosis
      plus decreased plasma membrane delivery of newly synthesized NHE3. Also, NHE3
      activity was inhibited by the CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H
      benzimidazole DMAT when wild-type NHE3 was expressed in fibroblasts and Caco-2
      cells, but the NHE3-S(719) mutant was fully resistant to DMAT. CK2 bound to the
      NHE3 C-terminal domain, between amino acids 590 and 667, a site different from
      the site it phosphorylates. CK2 binds to the NHE3 C terminus and stimulates basal
      NHE3 activity by phosphorylating a separate single site on the NHE3 C terminus
      (S(719)), which affects NHE3 trafficking.

PMID- 18614798
TI  - Phosphatidylinositol (4,5)-bisphosphate modulates Nox5 localization via an N
      terminal polybasic region.
AB  - Nox5, an EF-hand-containing reactive oxygen species (ROS)-generating NADPH
      oxidase, contains two conserved polybasic regions: one N-terminal (PBR-N),
      located between the fourth EF-hand and the first transmembrane region, and one C
      terminal (PBR-C), between the first and second NADPH-binding subregions. Here, we
      show that phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)], a major
      phosphoinositide in plasma membrane, binds to human Nox5 causing Nox5 to localize
      from internal membranes to the plasma membrane. Enzymatic modulation of
      PtdIns(4,5)P(2) levels in intact cells altered cell surface localization of Nox5
      in parallel with extracellular ROS generation. Mutations in PBR-N prevented
      PtdIns(4,5)P(2)-dependent localization of Nox5 to the plasma membrane and
      decreased extracellular ROS production. A synthetic peptide corresponding to PBR
      N bound to PtdIns(4,5)P(2), but not to PtdIns, whereas mutations in the PBR-N
      peptide abrogated the binding to PtdIns(4,5)P(2). Arginine-197 in PBR-N was a key
      residue to regulate subcellular localization of Nox5 and its interaction with
      PtdIns(4,5)P(2). In contrast, mutation in PBR-C did not affect localization.
      Thus, extracellular ROS production by Nox5 is modulated by PtdIns(4,5)P(2) by
      localizing Nox5 to the plasma membrane.

PMID- 18614799
TI  - Effect of 27nt small RNA on endothelial nitric-oxide synthase expression.
AB  - We have reported previously that the 27nt repeat polymorphism in endothelial
      nitric-oxide synthase (eNOS) intron 4--a source of 27nt small RNA--inhibits eNOS
      expression. In the current study, we have investigated how 27nt small RNA
      suppresses eNOS expression. Using a chromatin immunoprecipitation assay, we
      examined histone acetylation in the 27nt repeat element of eNOS intron 4, the
      promoter region up to -1486 bp, and the 5' enhancer region (-4583/-4223bp) in
      human aortic endothelial cells (HAECs) treated with 27nt RNA duplex. 27nt RNA
      duplex induced hyperacetylation in H3 (lysine8, 12, and 23) and H4 (lysine 9 and
      12) at the 27nt repeat element, which then interacted with nuclear actin, histone
      deacetylase 3 (HDAC3), and NonO proteins. In contrast, the histone H3 and H4
      became hypoacetylated at the eNOS core promoter. HAECs treated with 27nt RNA
      duplex had reduced eNOS expression, but treatment with either HDAC3 small
      interfering RNA or NonO siRNA significantly attenuated the 27nt small RNA-induced
      suppression. We further found that 27nt small RNA induced DNA methylation in a
      region approximately 750nt upstream of the intron 4 repeats, and a
      methyltransferase inhibitor reversed the effect on methylation and eNOS
      expression. Our study demonstrates that 27nt small RNA may suppress eNOS
      expression by altering histone acetylation and DNA methylation in regions
      adjacent to the 27nt repeat element and core promoter.

PMID- 18614801
TI  - Automatic recognition of corneal nerve structures in images from confocal
      microscopy.
AB  - PURPOSE: To devise a method for automatically tracing corneal nerves in confocal
      microscopy images. METHODS: Images were acquired with a confocal microscope. They
      were normalized and enhanced in luminosity and contrast. The nerves were
      recognized by applying a novel tracing algorithm, which includes Gabor filtering
      to enhance nerve visibility and postprocessing procedures to remove false
      recognitions and to link sparse segments into continuous structures. A prototype
      of the algorithm was implemented in commercial software and run on a personal
      computer. RESULTS: A retrospective evaluation of the automatic procedure was
      performed on a data set containing 90 images, from normal and non-normal
      subjects. The average percentage of correctly recognized nerves length with
      respect to total manually traced lengths of visible nerves was 80.4% in normal
      subjects and 83.8% on non-normal subjects; the average rate of false nerve length
      recognition (with respect to the total automatically traced length) was 6.5% in
      normal subjects and 9.1% in non-normal subjects. Correlation coefficients between
      manual and automatic lengths on the same image were 0.94, 0.95, and 0.86 in all,
      normal, and non-normal subjects, respectively. A further evaluation was performed
      on an independent set of 80 normal subject images, resulting in a correlation
      coefficient of 0.89 between manual and automatic nerve lengths. CONCLUSIONS:
      Automatic and manual length estimations on the same image were very well
      correlated, indicating that the automatic procedure is capable of correctly
      reproducing the differences in nerve length between different subjects.

PMID- 18614800
TI  - Myosin IIC: a third molecular motor driving neuronal dynamics.
AB  - Neuronal dynamics result from the integration of forces developed by molecular
      motors, especially conventional myosins. Myosin IIC is a recently discovered
      nonsarcomeric conventional myosin motor, the function of which is poorly
      understood, particularly in relation to the separate but coupled activities of
      its close homologues, myosins IIA and IIB, which participate in neuronal
      adhesion, outgrowth and retraction. To determine myosin IIC function, we have
      applied a comparative functional knockdown approach by using isoform-specific
      antisense oligodeoxyribonucleotides to deplete expression within neuronally
      derived cells. Myosin IIC was found to be critical for driving neuronal process
      outgrowth, a function that it shares with myosin IIB. Additionally, myosin IIC
      modulates neuronal cell adhesion, a function that it shares with myosin IIA but
      not myosin IIB. Consistent with this role, myosin IIC knockdown caused a
      concomitant decrease in paxillin-phospho-Tyr118 immunofluorescence, similar to
      knockdown of myosin IIA but not myosin IIB. Myosin IIC depletion also created a
      distinctive phenotype with increased cell body diameter, increased vacuolization,
      and impaired responsiveness to triggered neurite collapse by lysophosphatidic
      acid. This novel combination of properties suggests that myosin IIC must
      participate in distinctive cellular roles and reinforces our view that closely
      related motor isoforms drive diverse functions within neuronal cells.

PMID- 18614802
TI  - Suppression of activation and induction of apoptosis in RAW264.7 cells by
      amniotic membrane extract.
AB  - PURPOSE: Macrophages play a pivotal role in initiating, maintaining, and
      resolving host inflammatory/immune responses but may cause recalcitrant
      inflammation and tissue damage if not controlled. Clinically, amniotic membrane
      (AM) transplantation suppresses inflammation in ocular surface reconstruction.
      Experimentally, the authors and others have reported that AM facilitates
      macrophage apoptosis. However, it remains unclear whether such anti-inflammatory
      activity is retained in AM extract (AME). METHODS: Herein the authors demonstrate
      in resting and activated (by interferon [IFN]-gamma, lipopolysaccharide [LPS], or
      IFN-gamma/LPS) murine monocyte/macrophage RAW264.7 cells that AME suppresses cell
      spreading and reduces actin filaments determined by phalloidin staining and
      Western blotting of Triton X-100 extracted cell lysate. RESULTS: Western blot and
      immunocytochemistry staining showed AME downregulates the expression of such cell
      surface markers as CD80, CD86, and major histocompatibility complex class 2
      antigen. Cell growth/viability is inhibited whereas cell apoptosis is enhanced by
      AME. Accordingly, secreted proinflammatory cytokines such as TNF-alpha and IL-6
      are reduced, but anti-inflammatory cytokine IL-10 is upregulated. CONCLUSIONS:
      Collectively, these results suggest that, similar to amniotic membrane, AME
      retains anti-inflammatory activities and does so by downregulating activation and
      inducing apoptosis in macrophages.

PMID- 18614803
TI  - Basic fibroblast growth factor impact on retinoblastoma progression and survival.
AB  - PURPOSE: Chemotherapy resistance is a problem in the treatment of advanced
      retinoblastoma (RB). Since basic fibroblast growth factor (bFGF) is a survival
      factor for neural precursor cells, bFGF was evaluated as a growth and
      chemoresistance factor in RB. METHODS: bFGF expression was analyzed in the LH
      betaTag transgenic mouse model of RB and human RB cell lines by
      immunofluorescence, RT-PCR, and Western blot. Proliferation and apoptosis (TUNEL)
      assays were performed. RESULTS: bFGF levels significantly increased during
      tumorigenesis in transgenic RB, as a function of tumor status (P = 0.005). PCR
      and confocal microscopy confirmed that the human cell lines and primary tumors
      expressed bFGF. bFGF was localized to vascular and tumor cells and rarely to
      glial cells. Exogenous 18-kDa bFGF induced proliferation in two RB cell lines
      (WERI and Y79). Western blot analysis demonstrated 34-, 22-, and 18-kDa isoforms
      in transgenic RB and both cell lines. In TUNEL assays, chemoresistance to
      carboplatin-induced apoptosis was observed in the Y79 line, which expressed a
      higher ratio of high (34 kDa)- to low-molecular-weight bFGF isoforms, compared
      with the WERI line. Similar to other bFGF tumor studies, exogenous low-molecular
      weight (18 kDa) bFGF (1 ng) significantly enhanced carboplatin-induced apoptosis
      in the more chemosensitive WERI, but not the chemoresistant Y79 line.
      CONCLUSIONS: RB tumors produce significant amounts of bFGF, and the differential
      production and response to isoforms of bFGF may have implications for invasive
      tumor growth and chemoresistance.

PMID- 18614804
TI  - Specific metabolic properties of rat oculorotatory extraocular muscles can be
      linked to their low force requirements.
AB  - PURPOSE: To gain insight into the metabolic pathways of oculorotatory extraocular
      muscle (EOM) fiber types at the cellular level to explain their high fatigue
      resistance, rapid contraction, and low force output. METHODS: In consecutive
      sections of adult rat EOMs, the cross-sectional area (CSA) was calculated, and
      the activities of succinate-dehydrogenase (SDH) and alpha-glycerophosphate
      dehydrogenase (GPDH) were measured by quantitative histochemistry of different
      fiber types classified by the myofibrillar adenosine triphosphatase (mATPase)
      staining pattern. RESULTS: In the orbital regions, type 1 (fast) fibers were
      present, showing small CSA, medium SDH, and low GPDH activity. The type 2 (slow)
      fibers exhibited extremely small CSA and low SDH and GPDH activity. In the global
      region, fast types 3 to 5 fibers were found, forming a continuum with an inverse
      correlation between CSA and enzyme activity. SDH and GPDH activity showed an
      unusual positive relationship in contrast to the skeletal muscle fiber types. The
      type 6 fibers were slow forming a close and clearly separated group with medium
      CSA and extremely low SDH and low GPDH activity. CONCLUSIONS: Muscle fibers in
      adult rat EOMs show unique metabolic properties not seen in other skeletal
      muscles, covering their extraordinary functional demands. It can be speculated
      that the EOMs embedded within the orbit material do not need to perform with high
      force, and therefore they could develop extensive systems that ensure both
      fatigue resistance (many mitochondria) and fast contraction with high mATPase
      activity (a well-developed sarcotubular system).

PMID- 18614805
TI  - Progressive morphological and functional defects in retinas from alpha1 integrin
      null mice.
AB  - PURPOSE: The role of integrin/cell matrix interactions between the RPE and the
      basement membrane in retinal maintenance and function is not well characterized.
      In this study the functional importance of alpha1beta1 integrin for retinal
      pigment epithelial cell homeostasis and retinal health was assessed by comparing
      alpha1 integrin knockout mice with strain- and age-matched wild-type mice.
      METHODS: Immunolocalization and Western blot analysis of retinas and ARPE19 cells
      were performed to examine the expression of alpha1beta1 integrin in the RPE.
      Retinal abnormality was assessed by funduscopy, histology, and transmission
      electron microscopy. Progressive retinal damage was quantified by direct counting
      of rod photoreceptors. Light-induced translocation of arrestin and alpha
      transducin was documented by immunohistochemical analysis of retinal
      cryosections. RESULTS: Integrin alpha1beta1 localizes to the basal aspect of
      retinal pigment epithelial cells colocalizing with the basal lamina of the RPE.
      Integrin alpha1-null mice have delayed-onset progressive retinal degeneration
      associated with thickening of the basement membrane, dysmorphology of basal
      processes, synaptic malformations, and funduscopic abnormalities. Integrin alpha1
      null mice display marked delays in transducin translocation compared with dark
      adapted wild-type mice after exposure to light. CONCLUSIONS: Collectively, these
      data suggest an essential role for alpha1beta1 integrin/basement membrane
      interactions in the RPE in basement membrane metabolism and translocation of
      transducin in photoreceptors. This is the first report describing evidence
      supporting an essential role for integrin/basement membrane interaction in the
      RPE. Further, this report demonstrates a direct link between integrin alpha1beta1
      function in retinal pigment epithelial and molecular defects in photoreceptor
      cell function before retinal abnormality is apparent.

PMID- 18614806
TI  - The myosin II ATPase inhibitor blebbistatin prevents thrombin-induced inhibition
      of intercellular calcium wave propagation in corneal endothelial cells.
AB  - PURPOSE: Thrombin inhibits intercellular Ca(2+) wave propagation in bovine
      corneal endothelial cells (BCECs) through a mechanism dependent on myosin light
      chain (MLC) phosphorylation. In this study, blebbistatin, a selective myosin II
      ATPase inhibitor, was used to investigate whether the effect of thrombin is
      mediated by enhanced actomyosin contractility. METHODS: BCECs were exposed to
      thrombin (2 U/mL) for 5 minutes. MLC phosphorylation was assayed by
      immunocytochemistry. Ca(2+) waves were visualized by confocal microscopy with
      Fluo-4AM. Fluorescence recovery after photobleaching (FRAP) was used to
      investigate intercellular communication (IC) via gap junctions. ATP release was
      measured by luciferin-luciferase assay. Lucifer yellow (LY) uptake was used to
      investigate hemichannel activity, and Fura-2 was used to assay thrombin- and ATP
      mediated Ca(2+) responses. RESULTS: Pretreatment with blebbistatin (5 microM for
      20 minutes) or its nitro derivative prevented the thrombin-induced inhibition of
      the Ca(2+) wave. Neither photo-inactivated blebbistatin nor the inactive
      enantiomers prevented the thrombin effect. Blebbistatin also prevented thrombin
      induced inhibition of LY uptake, ATP release and FRAP, indicating that it
      prevented the thrombin effect on paracrine and gap junctional IC. In the absence
      of thrombin, blebbistatin had no significant effect on paracrine or gap
      junctional IC. The drug had no influence on MLC phosphorylation or on [Ca(2+)](i)
      transients in response to thrombin or ATP. CONCLUSIONS: Blebbistatin prevents the
      inhibitory effects of thrombin on intercellular Ca(2+) wave propagation. The
      findings demonstrate that myosin II-mediated actomyosin contractility plays a
      central role in thrombin-induced inhibition of gap junctional IC and of
      hemichannel-mediated paracrine IC.

PMID- 18614807
TI  - Mitochondrial defects and dysfunction in calcium regulation in glaucomatous
      trabecular meshwork cells.
AB  - PURPOSE: Disruption in intracellular calcium ion (Ca(2+)) homeostasis has major
      effects on health. Persistent Ca(2+) overload induces mitochondrial permeability
      transition pore (MPTP) opening, which prompts mitochondrial release of calcium
      (mCICR) and reactive oxygen species (ROS) into the cytosol which, in turn,
      compromises mitochondrial function. This study was conducted to examine
      intracellular Ca(2+) levels and mitochondrial vulnerability to Ca(2+) stress in
      trabecular meshwork (TM) of individuals with primary open-angle glaucoma (POAG).
      METHODS: Primary cultures of TM cells from POAG (GTM) and age-matched,
      nondiseased (NTM) eyes, obtained from postmortem donors eyes by standard surgical
      trabeculectomy, were treated with the following calcium regulators: the
      mitochondrial respiratory chain I inhibitor rotenone (ROT); the mitochondrial
      permeability transition pore (MPTP) inhibitors cyclosporine (Cys) and
      aristolochic acid (ArA); the Ca(2+) chelators BAPTA/AM or EDTA; the mitochondrial
      Ca(2+) uniporter inhibitor ruthenium red (RR); the Ca(2+)/Na(+) exchanger
      inhibitor trifluoperazine; and the inositol 1,4,5-triphosphate receptor type 3
      (IP3R) inhibitors 2-aminoethoxydiphenyl borane (2-APB) and xestospongin C (Xe-C).
      Ca(2+) concentrations in the cytoplasm ([Ca(2+)](c)) and mitochondria
      ([Ca(2+)](m)) were determined by confocal microscopy and flow cytometry with the
      fluorescent Ca(2+) indicators fluo-3/AM and rhod-2/AM, respectively.
      Mitochondrial membrane potential (DeltaPsim) was examined with the fluorescent
      probe tetramethylrhodamine ethyl ester (TMRE). The expression of cyclophilin D, a
      protein that induces MPTP opening was also measured. RESULTS: There was increased
      [Ca(2+)](c), [Ca(2+)](m), mCICR, MPTP opening, and expression of cyclophilin D
      and decreased DeltaPsim in POAG TM cells compared with control cells. ROT
      artificially exacerbated these conditions in GTM cells. Chelation of [Ca(2+)](c)
      and inhibition of IP3R and MPTP opening suppressed mitochondrial dysfunction and
      reduced the additional effects of ROT in GTM cells. CONCLUSIONS: POAG TM cells
      have defective mitochondrial function, which causes them to be abnormally
      vulnerable to Ca(2+) stress. The dysfunction in calcium regulation by these cells
      may contribute to the failure of this tissue to control IOP. Pharmacologic
      inhibitors of IP3R, MPTP opening, and cyclophilin D could have clinical
      implications for primary open-angle glaucoma.

PMID- 18614808
TI  - The human ubiquitin conjugating enzyme, UBE2E3, is required for proliferation of
      retinal pigment epithelial cells.
AB  - PURPOSE: Cell cycle progression is governed by the coordinated activities of
      kinases, phosphatases, and the ubiquitin system. The entire complement of
      ubiquitin pathway components that mediate this process in retinal pigment
      epithelial (RPE) cells remains to be identified. This study was undertaken to
      determine whether the human ubiquitin-conjugating enzyme, UBE2E3, is essential
      for RPE cell proliferation. METHODS: UBE2E3 expression and localization in
      telomerase-immortalized, human RPE cells was determined with a UBE2E3-specific
      antibody. The necessity for UBE2E3 in RPE proliferation was determined using
      small interfering (si)RNA to target the expression of the enzyme. Cell counts and
      immunolabeling for the proliferation marker Ki-67 and the cyclin-dependent kinase
      inhibitor p27(Kip1) were performed to assess the consequences of UBE2E3
      depletion. A mouse strain harboring a disrupted allele of UbcM2 (the mouse
      counterpart of UBE2E3) with the coding sequence for beta-galactosidase was used
      to track the developmental expression of the enzyme in murine RPE cells. RESULTS:
      UBE2E3 localized in the nucleus of the immortalized RPE cells. Depletion of the
      enzyme by siRNA resulted in a cell-cycle exit accompanied by a loss of Ki-67, an
      increase in p27(Kip1), and a doubling in cell area. Rescue experiments confirmed
      the specificity of the RNA interference. In vivo, UbcM2 was transcriptionally
      downregulated during RPE development in the mouse. CONCLUSIONS: UBE2E3 is
      essential for the proliferation of RPE-1 cells and is downregulated during RPE
      layer maturation in the developing mouse eye. These findings indicate that UBE2E3
      is a major enzyme in modulating the balance between RPE cell proliferation and
      differentiation.

PMID- 18614809
TI  - Ex vivo model of cerebrospinal fluid outflow across human arachnoid granulations.
AB  - PURPOSE: The brain's arachnoid membrane with granulations is an important
      biological barrier whose responsibilities include the transmission of
      cerebrospinal fluid (CSF) and the regulation of pressure. Membrane disturbance
      may cause changes that are difficult to replicate with animal models, suggesting
      the need for a model using human arachnoid membrane with granulations for the
      study of conditions such as Alzheimer disease, hydrocephalus, and pseudotumor
      cerebri. The authors detail the development and validation of an ex vivo model of
      CSF outflow across human arachnoid granulations (AGs) as an approximation of in
      vivo conditions. METHODS: Human AGs were perfused at normal physiological
      pressure in physiological and nonphysiological directions for permeability data.
      Fluorescent particle perfusion with electron microscopy identified outflow
      pathways through the AGs. RESULTS: This human ex vivo model demonstrated in vivo
      properties of unidirectionality, particle transport, and ultrastructure, similar
      to our 2005 in vitro model. The average baseline hydraulic conductivity in the
      physiological direction (n = 20) was 1.05 +/- 0.15 microL/min/mm Hg/cm(2)
      compared with 0.11 +/- 0.03 microL/min/mm Hg/cm(2) in the nonphysiological
      direction (n = 3) under statistically equivalent (P = 0.46) average normal
      physiological pressures (5.88 +/- 0.22 mm Hg and 6.14 +/- 0.23 mm Hg,
      respectively). CONCLUSIONS: The ex vivo model is feasible and herein
      demonstrated. These findings agree with in vivo CSF outflow. This model increases
      understanding of the clearance not only of CSF but also of metabolites through
      the arachnoid membrane. Additional evidence suggests, but does not yet prove,
      that CSF outflow may occur in a similar manner in the arachnoid membrane adjacent
      to the granulations, in addition to the flow through the AGs. This is a topic for
      further investigation.

PMID- 18614810
TI  - Screening tests for detecting open-angle glaucoma: systematic review and meta
      analysis.
AB  - PURPOSE: To assess the comparative accuracy of potential screening tests for open
      angle glaucoma (OAG). METHODS: Medline, Embase, Biosis (to November 2005),
      Science Citation Index (to December 2005), and The Cochrane Library (Issue 4,
      2005) were searched. Studies assessing candidate screening tests for detecting
      OAG in persons older than 40 years that reported true and false positives and
      negatives were included. Meta-analysis was undertaken using the hierarchical
      summary receiver operating characteristic model. RESULTS: Forty studies enrolling
      over 48,000 people reported nine tests. Most tests were reported by only a few
      studies. Frequency-doubling technology (FDT; C-20-1) was significantly more
      sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0-62) and Goldmann
      applanation tonometry (GAT; 45, 95% CrI 17-68), whereas threshold standard
      automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both
      more sensitive than GAT (41, 95% CrI 14-64 and 39, 95% CrI 3-64, respectively).
      GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP
      (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT,
      oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP,
      retinal photography, and GAT had relatively poor performance as single tests.
      These findings are based on heterogeneous data of limited quality and as such are
      associated with considerable uncertainty. CONCLUSIONS: No test or group of tests
      was clearly superior for glaucoma screening. Further research is needed to
      evaluate the comparative accuracy of the most promising tests.

PMID- 18614811
TI  - Retinal peripapillary nerve fiber layer thickness in neuromyelitis optica.
AB  - PURPOSE: To measure the thickness of retinal peripapillary nerve fibers
      throughout the course of neuromyelitis optica (NMO). METHODS: This study was of a
      cross-sectional design, examining the thickness of the retinal peripapillary
      nerve fiber layer by optical coherence tomography, in patients with NMO (n = 15;
      30 eyes), patients with multiple sclerosis (MS; n = 15; 30 eyes), and a control
      group (n = 23; 46 eyes). The thicknesses were acquired according to protocol with
      the fast RNFL (Retinal Nerve Fiber Layer) procedure. The study of visual function
      includes for each eye a determination of refraction, measurement of visual
      acuity, measurement of contrast vision, an analysis of color vision, and a
      frequency-doubling technology perimetry (FDTP). The main outcome measurements
      were the thickness of the retinal peripapillary nerve fibers, visual acuity, and
      scores of contrast vision. RESULTS: The average thickness of retinal
      peripapillary nerve fibers was respectively in the NMO, MS, and control group:
      65.44 +/- 24.19, 83.85 +/- 24.12, and 106.24 +/- 12.46 microm (P = 0.01). The
      average thickness of retinal peripapillary nerve fibers correlated to visual
      acuity, the scores of contrast vision, the scores of FDTP, and the number of
      episodes per patient (r = -0.58, P = 0.03). CONCLUSIONS: This is the first study
      to produce measurements of the thickness of retinal peripapillary nerve fibers
      during optic neuropathies of NMO. The optic neuropathies of NMO are also
      accompanied by an acute and chronic axonal loss, as clearly illustrated by the
      OCT.

PMID- 18614812
TI  - Hypothermia increases the gain of excitation-contraction coupling in guinea pig
      ventricular myocytes.
AB  - Components of excitation-contraction (EC)-coupling were compared at 37 degrees C
      and 22 degrees C to determine whether hypothermia altered the gain of EC coupling
      in guinea pig ventricular myocytes. Ca(2+) concentration (fura-2) and cell
      shortening (edge detector) were measured simultaneously. Hypothermia increased
      fractional shortening (8.3+/-1.7 vs. 2.6+/-0.3% at 37 degrees C), Ca(2+)
      transients (157+/-33 vs. 35+/-5 nM at 37 degrees C), and diastolic Ca(2+) (100+/
      9 vs. 60+/-6 nM at 37 degrees C) in field-stimulated myocytes (2 Hz). In
      experiments with high-resistance microelectrodes, the increase in contractions
      and Ca(2+) transients was accompanied by a twofold increase in action potential
      duration (APD). When voltage-clamp steps eliminated changes in APD, cooling still
      increased contractions and Ca(2+) transients. Hypothermia increased sarcoplasmic
      reticulum (SR) Ca(2+) stores (83+/-17 at 37 degrees C to 212+/-50 nM, assessed
      with caffeine) and increased fractional SR Ca(2+) release twofold. In contrast,
      peak Ca(2+) current was much smaller at 22 degrees C than at 37 degrees C (1.3+/
      0.4 and 3.5+/-0.7 pA/pF, respectively). In cells dialyzed with sodium-free
      pipette solutions to inhibit Ca(2+) influx via reverse-mode Na(+)/Ca(2+)
      exchange, hypothermia still increased contractions, Ca(2+) transients, SR stores,
      and fractional release but decreased the amplitude of Ca(2+) current. The rate of
      SR Ca(2+) release per unit Ca(2+) current, a measure of EC-coupling gain, was
      increased sixfold by hypothermia. This increase in gain occurred regardless of
      whether cells were dialyzed with sodium-free solutions. Thus an increase in EC
      coupling gain contributes importantly to positive inotropic effects of
      hypothermia in the heart.

PMID- 18614813
TI  - Affinity for MgADP and force of unbinding from actin of myosin purified from
      tonic and phasic smooth muscle.
AB  - Smooth muscle is unique in its ability to maintain force at low MgATP
      consumption. This property, called the latch state, is more prominent in tonic
      than phasic smooth muscle. Studies performed at the muscle strip level have
      suggested that myosin from tonic muscle has a greater affinity for MgADP and
      therefore remains attached to actin longer than myosin from phasic muscle,
      allowing for cross-bridge dephosphorylation and latch-bridge formation. An
      alternative hypothesis is that after dephosphorylation, myosin reattaches to
      actin and maintains force. We investigated these fundamental properties of smooth
      muscle at the molecular level. We used an in vitro motility assay to measure
      actin filament velocity (nu(max)) when propelled by myosin purified from phasic
      or tonic muscle at increasing [MgADP]. Myosin was 25% thiophosphorylated and 75%
      unphosphorylated to approximate in vivo conditions. The slope of nu(max) versus
      [MgADP] was significantly greater for tonic (-0.51+/-0.04) than phasic muscle
      myosin (-0.15+/-0.04), demonstrating the greater MgADP affinity of myosin from
      tonic muscle. We then used a laser trap assay to measure the unbinding force from
      actin of populations of unphosphorylated tonic and phasic muscle myosin. Both
      myosin types attached to actin, and their unbinding force (0.092+/-0.022 pN for
      phasic muscle and 0.084+/-0.017 pN for tonic muscle) was not statistically
      different. We conclude that the greater affinity for MgADP of tonic muscle myosin
      and the reattachment of dephosphorylated myosin to actin may both contribute to
      the latch state.

PMID- 18614814
TI  - Regulation of cell surface expression of functional pacemaker channels by a motif
      in the B-helix of the cyclic nucleotide-binding domain.
AB  - Previous studies have suggested that a portion of the cyclic nucleotide-binding
      domain (CNBD) of the hyperpolarization-activated cyclic nucleotide-gated channel
      2 (HCN2) "pacemaker" channel, composed of the A- and B-helices and the
      interceding beta-barrel, confers two functions: inhibition of channel opening in
      response to hyperpolarization and promotion of cell surface expression. The
      sequence determinants required for each of these functions are unknown. In
      addition, the mechanism underlying plasma membrane targeting by this subdomain
      has been limitedly explored. Here we identify a four-amino acid motif (EEYP) in
      the B-helix that strongly promotes channel export from the endoplasmic reticulum
      (ER) and cell surface expression but does not contribute to the inhibition of
      channel opening. This motif augments a step in the trafficking pathway and/or the
      efficiency of correct folding and assembly.

PMID- 18614815
TI  - Replacement of dietary saturated FAs by PUFAs in diet and reverse cholesterol
      transport.
AB  - Dietary intervention is the first and usually successful approach in the
      treatment of high LDL cholesterol (LDL-C) concentration, but it is frequently
      accompanied by a decrease in HDL concentration. We studied 14 male volunteers on
      two different diets, high saturated fatty acid (SFA) and high PUFA, in a
      crossover design to test whether a decrease in HDL can affect reverse cholesterol
      transport from relabeled macrophages. A significant decrease of LDL-C (in mmol/l)
      after a PUFA diet compared with an SFA diet from 3.15 +/- 0.65 to 2.80 +/- 0.56
      (P < 0.01) was accompanied by a significant decrease of HDL cholesterol (HDL-C)
      (in mmol/l) from 1.21 +/- 0.30 to 1.10 +/- 0.32 (P < 0.05). These changes did not
      affect cholesterol efflux (CHE) from macrophages (9.74 +/- 1.46% vs. 9.53 +/-
      1.41%). There was no correlation between individual changes of HDL-C and changes
      of CHE. It is concluded that the decrease of HDL-C after successful dietary
      intervention of LDL-C is not accompanied by a decrease of CHE.

PMID- 18614817
TI  - Influence of drugs and comorbidity on serum potassium in 15 000 consecutive
      hospital admissions.
AB  - BACKGROUND: Drug trials often exclude subjects with relevant comorbidity or
      comedication. Nevertheless, after approval, these drugs will be prescribed to a
      much broader collective. Our goal was to quantify the impact of drugs and
      comorbidity on serum potassium in unselected patients admitted to the hospital.
      METHODS: This was a retrospective pharmacoepidemiologic study in 15 000
      consecutive patients admitted to the medical department of the Kantonsspital St.
      Gallen, a 700-bed tertiary hospital in eastern Switzerland. Patients with
      'haemolytic' plasma and patients on dialysis or with an estimated glomerular
      filtration rate (GFR) <10 mL/min/1.73 m(2) were excluded. For the remaining 14
      146 patients, drug history on admission, age, sex, body weight, physical
      findings, comorbidity (ICD-10 diagnoses) and laboratory information (potassium
      and creatinine) were extracted from electronic sources. RESULTS: Estimated GFR
      was the strongest predictor of serum potassium (P < 0.0001). Angiotensin
      converting enzyme inhibitors, cyclosporine, loop diuretics and potassium-sparing
      diuretics all showed a significant effect modification with decreasing GFR (P <
      0.001). Similarly, in patients with liver cirrhosis a significantly stronger
      effect on potassium was found for angiotensin receptor blockers, betablockers and
      loop diuretics (P < 0.01). Several significant drug-drug interactions were
      identified. Diabetes, male sex, older age, lower blood pressure and higher body
      weight were all independently associated with higher serum potassium levels (P <
      0.001). The model explained 14% of the variation of serum potassium. CONCLUSIONS:
      The effects of various drugs on serum potassium are highly influenced by
      comorbidity and comedication. Although the presented model cannot be used to
      predict potassium in individual patients, we demonstrate that clinical databases
      could evolve as a powerful tool for industry-independent analysis of
      postmarketing drug safety.

PMID- 18614816
TI  - Cannabinoid (CB2) receptor deficiency reduces the susceptibility of macrophages
      to oxidized LDL/oxysterol-induced apoptosis.
AB  - Macrophage apoptosis is an important process in the pathophysiology of
      atherosclerosis. Oxidized low-density lipoproteins (OxLDL) are a major component
      of lesions and potently induce macrophage apoptosis. Cannabinoid receptor 2
      (CB2), the predominant macrophage cannabinoid receptor, modulates several
      macrophage processes associated with ongoing atherosclerosis; however, the role
      of CB2 in macrophage apoptosis is unknown. To determine if CB2 influences a
      macrophage apoptotic pathway relevant to atherosclerosis, we examined the effect
      of CB2 deficiency on OxLDL-induced macrophage apoptosis. In situ terminal
      transferase-mediated dUTP nick end labeling (TUNEL) analysis of resident
      peritoneal macrophages detected significantly fewer apoptotic CB2(-/-)
      macrophages than CB2(+/+) macrophages after incubation with OxLDL (27.9 +/- 4.7%
      vs. 61.9 +/- 8.5%, P < 0.001) or 7-ketocholesterol (7KC) (18.9 +/- 10.5% vs. 54.1
      +/- 6.9%, P < 0.001), an oxysterol component of OxLDL. Caspase-3 activity;
      proteolytic conversion of procaspase-3; and cleavage of a caspase-3 substrate,
      PARP, were also diminished in 7KC-treated CB2(-/-) macrophages. Furthermore, the
      deactivation of the prosurvival kinase, Akt, in response to 7KC was impaired in
      CB2(-/-) macrophages. These results suggest that CB2 expression increases the
      susceptibility of macrophages to OxLDL-induced apoptosis, in part, by modulating
      the effect of oxysterols on the Akt survival pathway and that CB2 may influence
      atherosclerosis by modulating lesional macrophage apoptosis.

PMID- 18614819
TI  - Expanding X-ray analysis.

PMID- 18614818
TI  - Preservation of peritoneal morphology and function by pentoxifylline in a rat
      model of peritoneal dialysis: molecular studies.
AB  - BACKGROUND: High-glucose (HG) content of dialysate accelerated peritoneal
      fibrosis. We investigated in vitro mechanisms and the in vivo potential of
      pentoxifylline (PTX) to prevent this fibrogenic process. METHODS: For human
      peritoneal mesothelial cell (HPMC) culture, a normal-glucose (NG, 5.5 mM) or HG
      (138 mM) medium was established through pilot experiments. The rat peritoneal
      dialysis (PD) model consists of four groups (n = 8): group 1, intraperitoneal
      (IP) HG (4.25%) solution; group 2, as group 1 plus daily IP PTX (4 mg/in 1 h);
      group 3, IP PTX and group 4 as control. RESULTS: In HPMC culture, PTX
      significantly prevented HG-stimulated gene and protein production of collagen and
      transforming growth factor-beta1 (TGF-ss1) (reduction rate of 72-81%). The p38
      mitogen-activated protein kinase (MAPK) pathway was activated significantly in HG
      treated HPMCs. Blockade of p38 MAPK by SB203580 (25 microM) or PTX (300
      microg/ml) resulted in an effective suppression of collagen and TGF-ss1 gene
      expression in HG-cultured HPMCs. In PD experimental animals, peritoneal thickness
      and collagen expression in the peritoneum were significantly increased in HG
      treated rats, and was attenuated by PTX (P < 0.01). Impaired peritoneal
      ultrafiltration (1.9 +/- 0.5 ml versus 2.4 +/- 0.4 ml, P < 0.05) and stimulated
      proinflammatory IL-6, MCP-1 and TGF-beta1 activation were observed in HG-treated
      rats. PTX well preserved the functional characteristics of peritoneum and
      cytokine profiles. CONCLUSIONS: These in vitro and in vivo data suggest that PTX
      may have therapeutic benefits for the prevention or retardation of peritoneal
      fibrosis.

PMID- 18614820
TI  - Chemical analysis of impurity boron atoms in diamond using soft X-ray emission
      spectroscopy.
AB  - To analyze the local structure and/or chemical states of boron atoms in boron
      doped diamond, which can be synthesized by the microwave plasma-assisted chemical
      vapor deposition method (CVD-B-diamond) and the temperature gradient method at
      high pressure and high temperature (HPT-B-diamond), we measured the soft X-ray
      emission spectra in the CK and BK regions of B-diamonds using synchrotron
      radiation at the Advanced Light Source (ALS). X-ray spectral analyses using the
      fingerprint method and molecular orbital calculations confirm that boron atoms in
      CVD-B-diamond substitute for carbon atoms in the diamond lattice to form covalent
      B-C bonds, while boron atoms in HPT-B-diamond react with the impurity nitrogen
      atoms to form hexagonal boron nitride. This suggests that the high purity diamond
      without nitrogen impurities is necessary to synthesize p-type B-diamond
      semiconductors.

PMID- 18614821
TI  - Characterization of calcium carbonate polymorphs with Ca K edge X-ray absorption
      fine structure spectroscopy.
AB  - Ca K edge X-ray absorption fine structure (XAFS) spectroscopy was utilized for
      the characterization and quantification of calcium carbonate polymorphs and their
      mixtures. The advantage of the XAFS is the small sample quantity required for
      measurements, and a flexible sample environment. The near-edge XAFS spectra of
      calcite, aragonite and vaterite were measured with the conversion electron yield
      (CEY) method, and the obtained spectra showed characteristic features that can be
      utilized as fingerprints. The quantification of mixed polymorphs was examined by
      using a linear combination fitting of reference XAFS spectra. Though the quality
      of the fits was satisfactory, discrepancies in the evaluated values were observed
      between those with X-ray diffraction (XRD) and XAFS. The nonuniformity of samples
      may be enhanced by the surface sensitivity of the CEY method.

PMID- 18614823
TI  - X-ray energy dependence of the properties of the focused beams produced by
      polycapillary X-ray lens.
AB  - We investigated X-ray energy distribution in an X-ray microbeam produced by a
      polycapillary X-ray lens in combination with a sealed-type X-ray tube. This
      polycapillary X-ray lens has an output focal distance (OFD) of approximately 15
      mm. The size of the X-ray microbeam and its OFD were estimated by using a wire
      scanning method. In our case, the sizes of the X-ray microbeams at the output
      focal distance were 49 microm for Mo L(alpha), 36 microm for W L(alpha), and 28
      microm for Mo K(alpha). The spot sizes depend on the energy of the X-ray
      fluorescence. The reason for the energy dependence is that X-ray capillary optics
      is based on the principle of propagation through glass capillaries by means of X
      ray total external reflection. The evaluated OFD values of Mo L(alpha) and Mo
      K(alpha) were slightly changed in 17 microm. However, a deviation of 100 microm
      from the OFD caused only a 3% increase of the focal spot size. Therefore, we
      concluded that the OFD showed no significant dependence on X-ray energy.

PMID- 18614822
TI  - Topographic trace-elemental analysis in the brain of Wistar rats by X-ray
      microfluorescence with synchrotron radiation.
AB  - Knowledge about the spatial distribution and the local concentration of trace
      elements in tissues is of great importance, since trace elements are involved in
      many biological functions of living organisms. However, there are few methods
      available to measure the spatial (two (three)-dimensional) elemental distribution
      in animal brain. X-ray microfluorescence with synchrotron radiation is a
      multielemental mapping technique, which was used in this work to determine the
      topographic of iron, zinc and copper in coronal sections of female Wistar rats of
      different ages. Young (14 days old) and middle-aged (20 months old) rats (n = 8)
      were analyzed. The measurements were carried out at the XRF beam line at the
      Synchrotron Light National Laboratory (Campinas, Brazil). Two-dimensional
      scanning was performed in order to study the tendency of elemental concentration
      variation. The acquisition time for each pixel was 10 s/step and the step size
      was 300 microm/step in both directions. It was observed that the iron
      distribution was more conspicuous in the cortical area, thalamus and bellow the
      thalamus. On the other hand, the zinc distribution was more pronounced in the
      hippocampus. The iron, copper and zinc levels increased with advancing age.
      Therefore, this study reinforces the idea that these elements are involved in the
      chemical mechanisms of the brain that induce some neurological diseases, since
      they are also present in high levels in specific areas of the brain, such as the
      hippocampus and the substantia nigra of patients with these disorders.

PMID- 18614824
TI  - Spatially resolved X-ray fluorescence analysis with a pyroelectric X-ray emitter.
AB  - A portable instrument for two-dimensional X-ray fluorescence imaging was
      assembled with an X-ray source using a pyroelectric crystal, which was driven by
      a 9-V dry battery, a Si-PIN detector, a slit, and pulse motors. Line scanning for
      a mug and a knife-edge-scan of an iron sheet were carried out using this
      spectrometer. The sensitivity of the spectrometer was sufficient for elemental
      analysis of a mug using a 1 mm(2) slit, and several elements, such as Co, Ni, Zn,
      Pb and Zr, were detected. The estimated spatial resolution using a 0.8-mm pinhole
      was 3.5 mm.

PMID- 18614825
TI  - K(alpha)/K(beta) ratios of fluorescence X-rays as an information source on the
      depth distribution of iron in a low Z matrix.
AB  - This paper describes how the K(alpha)/K(beta) count rate ratio of the
      characteristic X-rays of a given element can be applied to determine the depth at
      which a layer or a grain of that element is located. The theoretical background
      and a basic description of the K(alpha)/K(beta) technique are given in the
      introduction. The experimental part of the paper deals with measurements of thick
      standard pure iron, intermediately thick iron foils, and layers prepared with a
      powder of Prussian blue. All these specimens were analyzed alone, and they were
      also analyzed overlaid with a low Z matrix. The light matrix consisted of sheets
      of paper of known thickness. Paper was chosen, because we take into account the
      subsequent application of this technique to surveys of historical monuments. The
      relation between the K(alpha) count rate, the K(alpha)/K(beta) count rate ratio,
      and the distribution of iron in the paper matrix are presented here.

PMID- 18614826
TI  - Advancement of flow-based analysis with alternative chemical reactions and new
      devices for environmental and biological samples.
AB  - This review includes our researches and other methodologies related to flow-based
      techniques, such as flow injection analysis (FIA) and sequential injection
      analysis (SIA). The methods will demonstrate semi-and full automated FIA and SIA,
      including liquid-liquid and liquid-solid extraction. FIA using alternative
      chemical reactions in the aqueous solution was applied to the trace analysis of
      metals in biological and environmental samples. For durable liquid-liquid
      extraction, several phase separators were designed. Moreover, multi-channel FIA
      with newly designed flow cells and SIA with lab-on-valve devices have been used
      for the simultaneous and successive determination of metals and organic
      compounds. On-line solid phase extraction (SPE) has also been proposed for highly
      sensitive analysis of organic and inorganic compounds.

PMID- 18614827
TI  - HPLC separation of triacylglycerol positional isomers on a polymeric ODS column.
AB  - A polymeric ODS column was applied to the resolution of triacylglycerol
      positional isomers (TAG-PI), i.e. 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and 1,2
      dioleoyl-3-palmitoyl-rac-glycerol (OOP), with a recycle HPLC system. To
      investigate the ODS column species and the column temperatures for the resolution
      of a TAG-PI pair, a mixture of OPO and OOP was subjected to an HPLC system
      equipped with a non-endcapped polymeric, endcapped monomeric, endcapped
      intermediate, or non-endcapped monomeric ODS column at three different column
      temperatures (40, 25, or 10 degrees C). Only the non-endcapped polymeric ODS
      column achieved the separation of OPO and OOP, and the lowest column temperature
      (10 degrees C) showed the best resolution for them. The other pair of TAG-PI, a
      mixture of 1,3-dipalmitoyl-2-oleoyl-glycerol (POP) and 1,2-dipalmitoyl-3-oleoyl
      rac-glycerol (PPO) was also subjected to the system equipped with a non-endcapped
      polymeric or monomeric ODS column at five different column temperatures (40, 32,
      25, 17, and 10 degrees C). Thus, POP and PPO were also separated on only the non
      endcapped polymeric ODS column at 25 degrees C. However, no clear peak appeared
      at 10 degrees C. These results would indicate that the polymeric ODS stationary
      phase has an ability to recognize the structural differences between TAG-PI
      pairs. Also, the column temperature is a very important factor for separating the
      TAG-PI pair, and the optimal temperature would relate to the solubility of TAG-PI
      in the mobile phase. Furthermore, the recycle HPLC system provided measurements
      for the separation and analysis of TAG-PI pairs.

PMID- 18614828
TI  - Flow-injection spectrophotometric determination of azithromycin in pharmaceutical
      formulations using p-chloranil in the presence of hydrogen peroxide.
AB  - A flow-injection (FI) spectrophotometric procedure exploiting merging zones is
      proposed for the determination of azithromycin in pharmaceutical formulations.
      The method is based on the reaction of azithromycin with tetrachloro-p
      benzoquinone (p-chloranil) accelerated by hydrogen peroxide and conducted in a
      methanol medium, producing a purple-red color compound (lambda(max) = 540 nm).
      The FI system and the experimental conditions were optimized using a multivariate
      method. Beer's law is obeyed in a concentration range of 50 - 1600 microg mL(-1)
      with an excellent correlation coefficient (r = 0.9998). The detection limit and
      the quantification limit were 6.6 and 22.1 microg mL(-1), respectively. No
      interference was observed from the common excipients, and the recoveries were
      within 98.6 to 100.4%. The procedure was applied to the determination of
      azithromycin in pharmaceuticals with a high sampling rate (65 samples h(-1)). The
      results obtained by the proposed method were in good agreement with those
      obtained by the comparative method at 95% confidence level.

PMID- 18614829
TI  - Optimization of a flow injection system with amperometric detection for arsenic
      determination.
AB  - A selective and sensitive analytical procedure for rapid arsenic determination by
      gas-diffusion flow injection analysis with amperometric detection was developed.
      The method is based on the arsenite reduction by NaBH(4). Derived arsine diffuses
      through a PTF membrane into the acceptor flow stream and is amperometrically
      determined on a platinum working electrode. The limit of detection (3 sigma) at
      room temperature was 5 microg/dm(3) of As(III). The relative standard deviation
      for a 1 mg/dm(3) As(III) standard was 1.96% for six repetitive injections.
      Arsenic(V) was determined after its prereduction with potassium iodide. Arsenic
      determination was not interferred with by 1 mg/dm(3) Sb(III), 5 mg/dm(3) Sn(II),
      10 mg/dm(3) Se(IV), 1 mg/dm(3) As(V), 1 mg/dm(3) hydrasine, 1 mg/dm(3) Fe(II) or
      0.5 mg/dm(3) Fe(III) solution. The throughput of this method was 60 analyses per
      hour. This method was successfully applied to arsenic determination in some power
      plant waste water samples.

PMID- 18614830
TI  - Organic-inorganic composite cation-exchanger: poly-o-toluidine Zr(IV) phosphate
      based ion-selective membrane electrode for the potentiometric determination of
      mercury.
AB  - A new heterogeneous precipitate of an organic-inorganic composite cation
      exchanger poly-o-toluidine Zr(IV) phosphate was utilized for the preparation of a
      Hg(II) ion-sensitive membrane electrode for the determination of Hg(II) ions in
      real aqueous as well as in real samples. The electrode showed good potentiometric
      response characteristics, and displayed a linear log[Hg(2+)] versus EMF response
      over a wide concentration range of 1 x 10(-1) - 1 x 10(-6) M with a Nernstian
      slope of 30 mV per decade change in concentration with a detection limit of 1 x
      10(-6). The membrane electrode showed a very fast response time of 5 s and could
      be operated well in the pH range 2 - 8. The selectivity coefficients were
      determined by the mixed-solution method, and revealed that the electrode was
      selective in the presence of interfering cations; however most of these did not
      show significant interference in the concentration range of 1 x 10(-1) - 1 x 10(
      4) M. The lifetime of the membrane electrode was observed to be 120 days. The
      analytical utility of this electrode was established by employing it as an
      indicator electrode in the potentiometric titrations of Hg(2+) ions from a
      synthetic mixture as well as drain water.

PMID- 18614831
TI  - Atropine-selective membrane electrodes and relative selectivity concept.
AB  - TFPB was introduced as a charged ionophore for atropine selective electrodes.
      Typical Nernstian responses were found (57.78, 58.95 and 58.41 mV/decade) for PVC
      membrane electrodes incorporating NPOE, DOS, and DDP as plasticizers. They
      exhibited practical linear ranges of 9.1 x 10(-3) - 10(-6), 9.1 x 10(-3) - 10(-6)
      and 9.1 x 10(-3) - 10(-7) M, respectively. It works in the sub-micro scale of
      atropine concentrations. The optimum pH-range was 3.18 - 8.97. The selectivity
      coefficient values were estimated for different organic and inorganic cations.
      They were interpreted by using the "Relative Selectivity Concept", which was
      introduced for the first time. The new concept was applied for comparing the
      selectivity properties of previously reported electrodes. The effect of the
      presence of ephedrine, caffeine, glucose, Na(+), Ca(2+), and Mg(2+) on the
      calibration graphs of the electrodes was studied.

PMID- 18614832
TI  - An amperometric horseradish peroxidase inhibition biosensor for the determination
      of phenylhydrazine.
AB  - An amperometric horseradish peroxidase (HRP) inhibition biosensor has been
      substantially constructed by the help of N,N-dicyclohexylcarbodiimide (DCC), N
      hydroxysuccinimide (NHS). The preparation steps and the biosensor response to
      phenylhydrazine were monitored by electrochemical impedance spectroscopy (EIS),
      cyclic voltammetry, and chronoamperometry. The proposed biosensor could be
      applied to determine phenylhydrazine in a 0.10 M phosphate buffer solution
      containing 1.2 mM hydroquinone and 0.50 mM H(2)O(2) by phenylhydrazine,
      inhibiting the catalytic activity of the HRP enzyme in the reduction of H(2)O(2).
      The system was optimized to realize a reliable determination of phenylhydrazine
      in the range of 2.5 x 10(-7) to 1.1 x 10(-6) M with a detection limit of 8.2 x
      10(-8) M and a correlation coefficient of 0.999. The modified electrode displayed
      good reproducibility, sensitivity and stability for the determination of
      phenylhydrazine.

PMID- 18614833
TI  - Electrochemical aspects of the reverse micelle extraction of proteins.
AB  - The mechanism of the solvent extraction of cytochrome c (Cyt c) via reverse
      micelle formation was studied from an electrochemical point of view.
      Potentiometric measurements showed that the Galvani potential difference of the
      oil/water (O/W) interface played a crucial role in the spontaneous extraction of
      Cyt c with bis(2-ethylhexyl)sulfosuccinate (AOT). However, the dependence of the
      extraction efficiency on the concentration of an aqueous electrolyte (KCl) could
      be explained not by the effect of the interfacial potential, but by the change in
      the interfacial tension (gamma). Electrocapillary measurements showed that the
      adsorption of AOT anions to the O/W interface resulted in a significant decrease
      of gamma in a higher potential range, where reverse micelles were formed. The
      bottom level of gamma in the higher potential range was increased with [KCl]. The
      lower extraction efficiency for higher [KCl]'s was elucidated by a "size
      exclusion effect". This was also supported by water-content measurements by the
      Karl Fisher method.

PMID- 18614835
TI  - Characterization and quantification of fluoxymesterone metabolite in horse urine
      by gas chromatography/mass spectrometry.
AB  - Fluoxymesterone, an anabolic steroid with the 17alpha-methyl,17beta-hydroxy
      group, has been developed as an oral formulation for therapeutic purposes.
      However, it is also used illegally in racehorses to enhance racing performance.
      In this study, we detected 9alpha-fluoro-17,17-dimethyl-18-norandrostane-4,13
      dien-11beta-ol-3-one by gas chromatography/mass spectrometry (GC/MS), which has
      not been reported as a fluoxymesterone metabolite so far in horse. It was
      synthesized for use as a reference standard, and characterized on the basis of
      (1)H NMR and (13)C NMR spectra, as well as GC/MS EI mass spectra of TMS
      derivatives. It was excreted as the main metabolite in horse urine, and its
      reference standard could be synthesized easily. Therefore, this metabolite could
      be a useful target for a doping test of fluoxymesterone in racehorses.

PMID- 18614834
TI  - Gold nanoparticle-based surface enhanced Raman scattering spectroscopic assay for
      the detection of protein-protein interactions.
AB  - In the present work, a sensitive spectroscopic assay based on surface-enhanced
      Raman spectroscopy (SERS) using gold nanoparticles as substrates was developed
      for the rapid detection protein-protein interactions. Detection is achieved by
      specific binding biotin-modification antibodies with protein-stabilized 30 nm
      gold nanoparticles, followed by the attachment of avidin-modification Raman
      active dyes. As a proof-of-principle experiment, a well-known biomolecular
      recognition system, IgG with protein A, was chosen to establish this new
      spectroscopic assay. Highly selective recognition of IgG down to 1 ng/ml in
      solution has been demonstrated.

PMID- 18614836
TI  - Pulsed NMR study of the curing process of epoxy resin.
AB  - To analyze a curing process of epoxy resin in terms of molecular motion, we
      adapted a pulsed NMR method. Three kinds of (1)H spin-spin relaxation times
      (T(2L) (long), T(2S) (short) and T(2M) (intermediate)) were estimated from
      observed solid echo train signals as the curing process proceeded. A short T(2S)
      value below 20 micros suggests the existence of a motion-restricted chain, that
      is, cured elements of resin, and its fraction, P(S), sigmoidally increased with
      the curing time. On the other hand, the fraction of T(2L), P(L), decreased with
      the reaction time reciprocally against P(S), suggesting the disappearance of
      highly mobile molecules raised from pre-cured resin. The spin-lattice relaxation
      time, T(1), was also measured to check another aspect of molecular motion in the
      process. T(1) of the mixed epoxy resin and curing agent gradually increased just
      after mixing both of them. This corresponds to an increment of a less-mobile
      fraction, of which the correction time is more than 10(-6) s, and also means that
      the occurrence of a network structure whose mobility is strongly restricted by
      chemically bonded bridges between the epoxy resin and curing agent. The time
      courses of these parameters coincided with those of IR peaks pertinent to the
      curing reaction. Therefore, pulsed NMR is a useful tool to monitor the hardening
      process of epoxy resin in real time non-distractively in terms of the molecular
      motion of protons.

PMID- 18614837
TI  - Uptake of iodine and bromine by ion-exchange resins in aqueous solution.
AB  - The uptakes of molecular iodine and bromine by both strong acid cation (Dowex 50W
      X4 and X8) and strong base anion (Dowex 1-X4 and X8) exchange resins have been
      studied in aqueous solutions at 25 degrees C. An empirical formula for the amount
      of solute taken up by the resin in mmol per gram of dry resin, Q, as a function
      of the solute concentration in M (mol dm(-3)), C, was derived. Direct
      proportional relationships between Q and C have been found, except for the
      bromine-anion exchanger system. In contrast to the cation-exchange resin, the
      anion exchanger exhibits extremely high affinity for I(2) and Br(2).

PMID- 18614838
TI  - Formation of a liquid organic ion associate in aqueous solution and its
      application to the GF-AAS determination of trace cadmium in environmental water
      as a complex with 2-(5-bromo-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino)phenol.
AB  - The formation of a liquid organic ion associate in an aqueous sample was applied
      to the concentration and determination of cadmium in environmental water samples.
      Cadmium was converted into a complex with 2-(5-bromo-2-pyridylazo)-5-(N-propyl-N
      sulfopropylamino)phenol (5-Br-PAPS) in a 40-mL sample solution, and was extracted
      into a liquid ion associate of phenolsulfonate and benzethonium during phase
      formation. More than 400-fold enrichment was easily attained by this technique,
      because the volume of the liquid organic phase formed was very small, ca. 2
      microL. After dilution of the organic phase with a small volume of 2
      methoxyethanol, the cadmium in the solution was determined by GF-AAS. The
      detection limit was 0.09 ng/L (3sigma(b)). This method was applied to the
      determination of cadmium in river water and seawater.

PMID- 18614839
TI  - Signal enhancement for gene detection based on a redox reaction of [Fe(CN)(6)](4
      ) mediated by ferrocene at the terminal of a peptide nucleic acid as a probe with
      hybridization-amenable conformational flexibility.
AB  - Electrochemically enhanced DNA detection was demonstrated by utilizing the couple
      of a synthesized ferrocene-terminated peptide nucleic acid (PNA) with a cysteine
      anchor and a sacrificial electron donor [Fe(CN)(6)](4-). DNA detection sensors
      were prepared by modifying a gold electrode surface with a mixed monolayer of the
      probe PNA and 11-hydroxy-1-undecanethiol (11-HUT), protecting [Fe(CN)(6)](4-)
      from any unexpected redox reaction. Before hybridization, the terminal ferrocene
      moiety of the probe was subject to a redox reaction due to the flexible probe
      structure and, in the presence of [Fe(CN)(6)](4-), the observed current was
      amplified based on regeneration of the ferrocene moiety. Hybridization decreased
      the redox current of the ferrocene. This occurred because hybridization
      rigidified the probe structure: the ferrocene moiety was then removed from the
      electrode surface, and the redox reaction of [Fe(CN)(6)](4-) was again prevented.
      The change in the anodic current before and after hybridization was enhanced 1.75
      fold by using the electron donor [Fe(CN)(6)](4-). Sequence-specific detection of
      the complementary target DNA was also demonstrated.

PMID- 18614840
TI  - On-line liquid chromatography and circular dichroism detection of stereo-isomers
      of alpha-tocopherol derivatives generated by an electrochemical reaction.
AB  - The electrochemical oxidation of (+/-)-alpha-tocopherol on a porous graphite
      electrode was performed in the presence of methanol, and successive separation
      and detection of the products were performed by an on-line liquid
      chromatography/mass spectrometry system. Three products were identified, one of
      which was determined to be alpha-tocopheryl quinone, because its m/z was 469
      [M+Na](+). The other two products showed identical mass and UV spectra, and were
      suspected to be diastereomers of 9-methoxy-alpha-tocopheron, because their
      molecular weights were m/z 483 [M+Na](+), and also because it is known that the
      chemical oxidation of alpha-tocopherol by benzoyl peroxide or N-bromosuccinimide
      in the presence of methanol should provide 9-methoxy-alpha-tocopheron. To confirm
      that these two compounds were diastereomers, a circular dichroism detector was
      used. The signs of both peaks detected by the circular dichroism detector at 230
      nm were opposite. In addition to observations of identical mass and ultraviolet
      spectra, these results indicated that the two products were diastereomers of 9
      methoxy-alpha-tocopheron, whose stereochemistry is different at the newly
      generated chiral center of the 9-position. The on-line use of a circular
      dichroism detector with an electrochemical cell/liquid chromatography system may
      expand the utility of the system to study the metabolism of a chiral drug.

PMID- 18614841
TI  - Determination of particle size by using incidence-angle dependence of spectral
      intensity for particle-size-measurement method by applying infrared attenuated
      total-reflection technique and its simulations by using algebraic-simultaneous
      equations.
AB  - A method using an incidence-angle dependence of the spectral intensity was
      proposed to determine a particle size in a particle-size measurement by applying
      an infrared attenuated-total-reflection (ATR) technique. A formula, which is
      proportional to the infrared ATR-spectral intensity, was constructed as a
      function of the particle size, amount of particles, and incidence angle, psi. Its
      psi dependences were calculated for SiO(2) particles of less than a mono layer on
      a Ge prism, and differed at every particle size. Some simulations of determining
      both particle size and particle amount were carried out for the samples of
      particles with sizes of 1 to 3 kinds by using algebraic-simultaneous equations
      with the software of Mathematica 5.2, and resulted in showing its usefulness.

PMID- 18614842
TI  - Use of radial basis function networks and near-infrared spectroscopy for the
      determination of total nitrogen content in soils from Sao Paulo State.
AB  - Total nitrogen has been determined by using a model developed between the
      conventional chemical measurements and diffuse reflectance spectra in the near
      infrared region. Samples (244) from different types of soils with total nitrogen
      contents ranging from 0.20 to 13.60% (m/m) were modeled by partial least-squares
      regression (PLS), multi-layer perceptron feed-forward networks (MLP) and radial
      basis function networks (RBFN). The RBFN model produced a better square error of
      prediction (SEP) of 0.048 and R(2) = 0.93 in a procedure that is simpler, faster
      and less dependent on the initial conditions.

PMID- 18614844
TI  - A new murine model of allergic rhinitis by repeated intranasal Cry j 1 challenge.
AB  - To evaluate the long-lasting effects of new therapeutic approaches to allergies,
      we established a new model of allergic rhinitis by repeated challenges with
      intranasal Cry j 1, a common Japanese cedar (Cryptomeria japonica) pollen
      allergen, in B10.S mice. We sensitized B10.S mice subcutaneously with Cry j
      1/alum three times at 1-week intervals. Five weeks after the final sensitization,
      we challenged the mice by instilling Cry j 1 intranasally for 5 consecutive days
      starting 1 day after intranasal histamine pretreatment (challenge-1). We
      challenged the mice by instilling histamine and Cry j 1 intranasally again 12
      weeks later (challenge-2). There were significantly more sneezes after challenge
      2 than challenge-1. Cry j 1-specific IgE levels in serum were significantly
      increased in both challenge-1 and 2 after continuous nasal antigen challenge.
      Serum levels of anti-Cry j 1 IgE in challenge-2 was 2.3 times higher than after
      challenge-1. Thus, we have established a new model of seasonal allergic rhinitis
      in B10.S mice by repeated intranasal antigen challenge, and this model may help
      elucidate mechanisms of allergic rhinitis and the development of new drugs.

PMID- 18614845
TI  - Association between salivary levels of chromogranin A and periodontitis in older
      Japanese.
AB  - The relationship between periodontitis and stress-related hormones is poorly
      understood. In this cross-sectional study we investigated the associations
      between the stress-related hormone, chromogranin A (CgA) and periodontitis in
      healthy community-dwelling elderly subjects aged 60 years old and older. A total
      of 171 subjects (85 males, 86 females; mean age of 68.4 +/- 4.46 (SD) years old)
      participated, all of whom were living independently. Stimulated whole saliva
      samples were collected and CgA levels were determined, while a medical
      questionnaire regarding medical conditions and lifestyle was also administered.
      Clinical examinations included probing depth (PD), bleeding on probing (BOP), and
      clinical attachment loss (CAL). When the subjects were divided into two groups
      based on periodontitis severity, the salivary CgA levels were significantly
      higher in subjects with severe PD or CAL. Multiple regression analysis showed
      that higher CgA level was significantly associated with greater numbers of teeth
      with severe PD or CAL, after adjusting for confounding variables. In this first
      known report of the association between CgA level and periodontitis, our results
      suggest a close relationship between the extent and severity of periodontitis and
      salivary level of CgA in healthy elderly subjects.

PMID- 18614846
TI  - Involvement of cytoskeletal integrity in the regulation of Cl- and amylase
      secretion from rat parotid acinar cells.
AB  - The cytoskeleton serves as a signal modulator for Ca2+ and cAMP-regulated cell
      functions including the secretion of ions and granule contents. The interaction
      between Ca2+ and cAMP signaling systems potentiates amylase secretion and
      suppresses Cl- secretion in the parotid glands. In this study, we investigated
      the role of the cytoskeleton in the modulation of Cl- and amylase secretion from
      rat parotid acinar cells upon activation of each intracellular signaling system
      and their interaction. Cytochalasin D markedly inhibited the Ca2+-activated
      outwardly rectifying Cl- current at positive membrane potentials and carbachol
      (CCh)-induced Cl- currents in the whole-cell configuration at -80 mV, whereas
      colchicine enhanced Cl- currents. Cytochalasin D, but not colchicine, markedly
      inhibited CCh-induced Cl- secretion. Synergistic actions of CCh and forskolin on
      Cl- and amylase secretion were observed even in the presence of cytochalasin D.
      These results suggest that the synergistic effects of Ca2+ and cAMP signaling
      systems on amylase and Cl- secretion do not require actin filament integrity but
      that secretion by the two signals themselves does require actin filament
      integrity.

PMID- 18614847
TI  - Differentiation-associated alteration in gene expression of importins and
      exportins in human leukemia HL-60 cells.
AB  - Employing the DNA microarray technique, we previously reported the alteration in
      gene expression of nucleocytoplasmic transport factors, importins and exportins,
      induced by 1,25-dihydroxyvitamin D3 (DVD) in human leukemia HL-60 cells. Here, we
      used the quantitative reverse transcription-polymerase chain reaction method to
      confirm such previous findings, and compared them with those from the cells
      treated with all-trans-retinoic acid (ATRA). The results indicated that the gene
      expression of the transport factors examined was mostly down-regulated following
      differentiation induced by DVD and ATRA, but importin alpha5 gene expression was
      up-regulated in either case. The differences were found in the gene expression of
      importin alpha3 and exportin 6 between the cells after treatments with DVD and
      ATRA. These variations may be related to the difference between HL-60 cell
      lineages differentiating into monocytes/macrophages and granulocytes. The present
      findings provide further evidence to support the important roles of importins and
      exportins in cell differentiation.

PMID- 18614848
TI  - Brain-derived neurotrophic factor (BDNF) prevents the development of diabetes in
      prediabetic mice.
AB  - We previously reported that peripheral injection of brain-derived neurotrophic
      factor (BDNF) exhibits hypophagic and hypoglycemic effects in obese hyperglycemic
      animals, indicating its antiobesity and antidiabetic effects. Since previous
      studies were focused on the effect of BDNF on overt diabetic animals with severe
      hyperglycemia, there was no evidence whether BDNF is effective or not for the
      development of diabetes in prediabetic animal models. Therefore, we evaluated the
      effect of BDNF on preventing the development of diabetes in db/db mice. First, we
      characterized age-related changes in the pathophysiology of diabetes in db/db
      mice. We chose 8 week-old db/db mice as the early diabetic stage (early
      intervention study) and 4 week-old db/db mice as the prediabetic stage
      (prevention study). Next, we examined the effects of BDNF on the progression of
      diabetes in early diabetic db/db mice. In the early intervention study using 8
      week-old db/db mice, intermittent treatment with BDNF prevented the deterioration
      in hyperglycemia. Lastly, we examined the preventive effects of BDNF on the
      development of diabetes in prediabetic db/db mice. In the prevention study using
      4 week-old db/db mice, treatment with BDNF prevented the age-related increase in
      blood glucose concentration. These results showed for the first time that BDNF
      prevents the development of diabetes in prediabetic db/db mice.

PMID- 18614849
TI  - Possible role of the RhoC/ROCK pathway in progression of clear cell renal cell
      carcinoma.
AB  - To clarify the role of the Rho small GTP-binding protein (Rho) and its major
      downstream target, ROCK (Rho-associated serine-threonine protein kinase), in
      progression of renal cell carcinoma (RCC), we examined mRNA expression for Rho
      and ROCK genes in surgical specimen of RCC tissues from 78 Japanese patients and
      in the corresponding non-tumor tissues originating from the same patient using a
      real-time reverse transcription polymerase chain reaction (RT-PCR). Expression of
      mRNA for RhoA did not differ between tumor and non-tumor tissues. RhoB mRNA
      expression was higher in the tumor (P < 0.05), but expression was not associated
      with tumor grade, stage, or prognosis. However, degree of RhoC and ROCK mRNA
      expression was related to tumor grade (P < 0.05) and stage (P < 0.0001). A
      positive relationship was seen between expression of mRNA for RhoC and that for
      ROCK in tumor tissues (P < 0.0001). Kaplan-Meier plots showed high RhoC and ROCK
      mRNA expression to be negatively associated with overall survival (P < 0.0001).
      Multivariate analysis showed mRNA expression of RhoC and ROCK to be independent
      poor prognostic factors concerning overall survival. Our findings implicate the
      RhoC/ROCK pathway in carcinogenesis and progression of RCC, indicating that
      RhoC/ROCK may be a useful prognostic marker and a possible molecular target for
      treatment of the disease.

PMID- 18614850
TI  - Effects of estrogens on proliferation and differentiation of neural
      stem/progenitor cells.
AB  - We investigated the effect of the female hormone 17beta-estradiol (E2) and the
      hormone mimic bisphenol A (BPA) on the proliferation and differentiation of rat
      neural stem/progenitors cells (NS/PCs) cultured from the telencephalon of
      embryonic day-15 rats. Basic fibroblast growth factor (FGF-2) is a potent mitogen
      of early generated NS/PCs, and is used for the proliferation of NS/PCs in vitro.
      Administration of E2 or BPA alone to the NS/PCs stimulated their proliferation in
      the absence but not in the presence of FGF-2. E2- or BPA-treatment increased the
      ratio of the oligodendrocytes generated from the NS/PCs to total cells; however,
      this ratio did not change when the cells were stimulated with platelet-derived
      growth factor (PDGF), a mitogen for oligodendrocyte precursors, or with
      neurotrophin-3, an oligogenic factor for glial progenitor cells. These results
      suggest that estrogens would influence the fate of NS/PCs when the cells are
      poorly supplied with mitogens or differentiation factors during the early stages
      of neurogenesis.

PMID- 18614851
TI  - Time-suppression test using a colorimetric probe (alamarBlue) that measures
      bacterial metabolic activity.
AB  - We developed a time-suppression test using alamarBlue, which will allow
      estimation of the cidal or static nature of antimicrobials very easily and
      quickly. As an example, the effects of vancomycin, linezolid, and daptomycin on a
      representative strain of Staphylococcus aureus were estimated.

PMID- 18614852
TI  - PGC-1alpha Gly482Ser polymorphism is associated with the plasma adiponectin level
      in type 2 diabetic men.
AB  - Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha)
      is a multifunctional transcriptional regulator for the pathways controlling
      mitochondrial biogenesis, oxidative metabolism, and glucose homeostasis. Genetic
      studies have suggested that Gly482Ser polymorphism of the PGC-1alpha gene is
      associated with a higher risk of type 2 diabetes, obesity, and hypertension.
      Adiponectin is an antidiabetic and antiatherogenic adipocytokine that is
      specifically produced by adipose tissue, and the transcription of the adiponectin
      gene is regulated by PPARgamma. In this study, we examined the effect of
      Gly482Ser polymorphism on the plasma adiponectin level in Japanese type 2
      diabetics. The Gly482Ser genotype was associated with a lower plasma adiponectin
      level in type 2 diabetic men, but not in type 2 diabetic women. The impact of
      this variation on the adiponectin promoter was also assessed by a reporter gene
      assay, but there was no significant difference between activation by the wild
      type and Gly482Ser- PGC-1alpha proteins, indicating that this variation itself
      has no functional effect. Evaluation of the pattern of linkage disequilibrium
      revealed that the Gly482Ser polymorphism is located in the largest linkage
      disequilibrium block of the PGC-1alpha gene. Therefore the observed gender
      specific association between PGC-1alpha and the plasma adiponectin level may
      reflect linkage disequilibrium of Gly482Ser polymorphism with other causative
      variations.

PMID- 18614853
TI  - Insulin enhancement of cytokine-induced coagulation/inflammation-related gene
      transcription in hepatocytes.
AB  - Hyperinsulinemia is a known risk factor for cardiovascular events, but its
      molecular basis is not completely understood. In this study, we examined the
      effects of insulin alone, or insulin and proinflammatory cytokines, on the
      expression of inflammation/coagulation-related genes in hepatocytes. We found
      that, in the HepG2 human hepatocyte cell line, insulin stimulated the
      transcriptional activity of plasminogen activator inhibitor 1 (PAI-1), fibrinogen
      gamma and C-reactive protein (CRP) genes in time- and dose-dependent manners.
      These effects were completely inhibited by MAP kinase inhibitor PD98059, but not
      by PI3 kinase inhibitor wortmannin. As previously reported, proinflammatory
      cytokines like interleukin 1beta and interleukin 6 showed stimulatory effects on
      the expression of these genes, and we now found that the combination of insulin
      and the cytokines showed more than additive effects in most cases. Interleukin
      1beta and insulin also cooperatively increased the endogenous mRNA level of PAI
      1. These results suggest that the coexistence of high insulin and cytokines may
      induce inflammation and hypercoagulation in a synergistic manner. This may partly
      explain why the accumulation of multiple risk factors, especially
      hyperinsulinemia caused by insulin resistance and enhanced production of
      proinflammatory cytokines, results in inflammation, thrombosis, and
      cardiovascular events in metabolic syndrome.

PMID- 18614854
TI  - Hypercalcemia during pregnancy, puerperium, and lactation: review and a case
      report of hypercalcemic crisis after delivery due to excessive production of PTH
      related protein (PTHrP) without malignancy (humoral hypercalcemia of pregnancy).
AB  - Hypercalcemia during pregnancy or after delivery is uncommon, and mostly
      associated with primary hyperparathyroidism (PHPT). If unrecognized, it may
      increase maternal and fetal morbidity. In a very few patients with PHPT,
      hypercalcemic crisis develops during pregnancy and particularly after delivery,
      since calcium transport from the mother to the fetus is abruptly disrupted.
      Hypercalcemia may also develop in pregnant women due to PTH-related protein
      (PTHrP)-producing malignant tumors (humoral hypercalcemia of malignancy). Since
      PTHrP is produced physiologically in fetal and maternal tissues, hypercalcemia
      may occasionally develop during pregnancy, puerperium, and lactation due to
      excessive production of PTHrP in the placenta and/or mammary glands. PTHrP may
      also be involved in milk-alkali syndrome that develops during pregnancy. Although
      non-malignant hypercalcemia is usually mild, we report a 28-years-old pregnant
      woman who developed hypercalcemic crisis after normal delivery of an infant. On
      the first postpartum day, the corrected serum calcium concentration increased to
      19.4 mg/dl with a markedly increased serum level of PTHrP (28.4 pmol/L) (normal
      <1.1 pmol/L). After administration of saline and pamidronate, the serum levels of
      calcium and PTHrP rapidly normalized. Extensive examination revealed no malignant
      lesion, suggesting that the placenta may have been producing an excessive amount
      of PTHrP (humoral hypercalcemia of pregnancy). We review case reports of non
      malignant hypercalcemic crisis associated with pregnancy indexed in PubMed in
      which serum levels of intact PTH and/or PTHrP were described, and stress that
      rapid control of hypercalcemia is mandatory to save the life of the mother and
      the infant.

PMID- 18614855
TI  - Metronomic chemotherapy and tumor immunomodulation.

PMID- 18614856
TI  - Somatic mutations to CSMD1 in colorectal adenocarcinomas.
AB  - The short arm of chromosome 8 is frequently deleted in advanced human colorectal
      cancers, suggesting the presence of one or more tumor suppressor genes having a
      major role in tumor progression and metastasis. Comprehensive sequencing of over
      18,000 genes in colon and breast cancers identified somatic mutations in CUB and
      Sushi Multiple Domains 1 Gene (CSMD1)which is located on the p arm of chromosome
      8. In this report, we describe a novel, robust, high-throughput gene mutation
      profiling strategy based on massively parallel picotiter plate pyrosequencing and
      have used this approach to identify additional somatic mutations to CSMD1 in
      early and late stage colorectal cancers. Using this strategy, we identified five
      nonsynonymous somatic mutations in CSMD1 among 26 colorectal cancers.
      Interestingly, these mutations occurred predominantly in advanced colorectal
      tumors,suggesting a role for CSMD1 in the development of late-stage metastatic
      disease.

PMID- 18614857
TI  - Broken beyond repair. Damaging DNA in glioblastoma cells with radiation  and
      camptothecin.

PMID- 18614858
TI  - Cancer gene therapy of adenovirus-mediated anti-4-1BB scFv  in immunocompetent
      mice.
AB  - The use of immunostimulatory molecule genes aiming at enhancing anti-tumor
      immunity has emerged as a new approach to treat cancers. 4-1BB signaling, an
      important costimulatory pathway delivering a signal for T cell activation,
      survival and growth, has become one of the most promising targets for cancer
      immunotherapy. In this work, a recombinant nonreplicative adenovirus (Ad.4-1BB
      scFv) carrying a single-chain Fv fragments (scFv) specific for 4-1BB gene (anti-4
      1BB scFv) was generated, haracterized and explored for its stimulation of anti
      tumor immunity in immunocompetent C57BL/6 mice. Ad.4-1BB scFv could efficiently
      infect murine hepatoma Hepa 1-6 cells and induce anti-4-1BB scFv expression on
      the cell surface. Moreover, Ad.4-1BB scFv did not cause obvious cytotoxicity
      effect on human and murine tumor cell lines (A549, PLC/PRF/5, Hepa 1-6 and TC-1)
      even at a high MOI, which suggested Ad.4-1BB scFv had no direct effect on tumor
      cells. Intratumoral injection of Ad.4-1BB scFv to established Hepa 1-6 tumors
      significantly suppressed the tumor growth in C57BL/6 mice. The anti-tumor effect
      might be mainly attributed to the anti-4-1BB scFv-mediated immune activity, as
      evidenced by enhanced interferon-gamma-producing splenic cells and increased
      lymphocytes infiltration in the tumor microenvironment. These results indicated
      that nonreplicative adenovirus carrying the anti-4-1BB scFv gene possessed
      powerful in vivo anti-tumor efficacy and might be a valuable tool for cancer
      immunotherapy.

PMID- 18614859
TI  - Shining the spotlight on shed KRAS in pancreatic cancer.

PMID- 18614861
TI  - Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir
      in treatment-naive HIV-1-infected patients at week 48.
AB  - BACKGROUND: The present primary analysis of AntiRetroviral Therapy with TMC114
      ExaMined In naive Subjects (ARTEMIS) compares the efficacy and safety of once
      daily darunavir/ritonavir (DRV/r) with that of lopinavir/ritonavir (LPV/r) in
      treatment-naive patients. METHODS: Patients with HIV-1 RNA at least 5000
      copies/ml were stratified by HIV-1 RNA and CD4 cell count in a phase III, open
      label trial, and randomized to receive DRV/r 800/100 mg qd or LPV/r 800/200 mg
      total daily dose (bid or qd) plus fixed-dose tenofovir and emtricitabine for 192
      weeks. The primary objective was to demonstrate non-inferiority of DRV/r as
      compared with LPV/r in HIV-1 RNA less than 50 copies/ml per-protocol time-to-loss
      of virologic response at 48 weeks. RESULTS: Six hundred and eighty-nine patients
      were randomized and treated; mean baseline HIV-1 RNA: 4.85 log10 copies/ml and
      median CD4 count: 225 cells/microl. At 48 weeks, 84% of DRV/r and 78% of LPV/r
      patients achieved HIV-1 RNA less than 50 copies/ml (estimated difference = 5.6
      [95% confidence interval -0.1-11]%), demonstrating non-inferiority of DRV/r as
      compared with LPV/r (P < 0.001; per-protocol time-to-loss of virologic response).
      Patients with HIV-1 RNA at least 100 000 copies/ml had a significantly higher
      response rate with DRV/r (79%) versus LPV/r (67%; P < 0.05). Median CD4 cell
      count increases (non-completer = failure; cells/mul) were 137 for DRV/r and 141
      for LPV/r. DRV/r had a lower incidence of possibly treatment-related grade 2-4
      gastrointestinal-related adverse events (7 versus 14%) and treatment-related
      moderate-to-severe diarrhea (4 versus 10%) than LPV/r. Adverse events leading to
      discontinuation were DRV/r: 3% and LPV/r: 7%. CONCLUSION: DRV/r 800/100 mg qd was
      non-inferior to LPV/r 800/200 mg at 48 weeks, with a more favorable safety
      profile. Significantly higher response rates were observed with DRV/r in patients
      with HIV-1 RNA at least 100 000 copies/ml. DRV/r 800/100 mg offers a new
      effective and well tolerated once-daily, first-line treatment option for
      treatment-naive patients.

PMID- 18614862
TI  - Care of HIV patients with chronic hepatitis B: updated recommendations from the
      HIV-Hepatitis B Virus International Panel.
AB  - Nearly 10% of the estimated 36 million people having HIV worldwide suffer from
      chronic hepatitis B virus (HBV) infection. The advent of new antiviral agents
      against HBV and the recent availability of improved molecular diagnostic tools
      have revolutioned the management of HIV/HBV coinfected patients. The present
      study represents an update of the current knowledge about HBV/HIV coinfection and
      an intent to provide practical advise about how to give the best care to HIV
      infected persons with chronic hepatitis B.

PMID- 18614863
TI  - Massively parallel pyrosequencing in HIV research.

PMID- 18614864
TI  - Transmission of HIV-1 minority-resistant variants and response to first-line
      antiretroviral therapy.
AB  - BACKGROUND: The transmission of drug-resistant HIV-1 can impair the virological
      response to antiretroviral therapy. Minority-resistant variants have been
      detected in acute seroconverters. We investigated the clinical relevance of the
      detection of majority and minority-resistant variants in an observational study
      in antiretroviral therapy naive, recently infected patients. METHODS: We included
      patients infected between 1996 and 2005, with a plasma sample obtained less than
      18 months after seroconversion and prior to antiretroviral therapy initiation.
      Majority-resistant variants were determined by direct population sequencing.
      Minority-resistant variants were searched by allele-specific PCR for the
      mutations K103N and M184V in reverse transcriptase and L90M in protease. The
      association between resistance and viroimmunological response to antiretroviral
      therapy was estimated by using a piecewise linear mixed model. RESULTS: Majority
      resistant variants were detected in 23/172 (13.4%) patients. Patients with
      majority-resistant variants had a lower mean plasma viral load and higher mean
      CD4 cell count at baseline compared with those without resistance. The decrease
      in viral load between 1 and 6 months on antiretroviral therapy was significantly
      steeper in patients with sensitive viruses compared with those with majority
      resistant variants (P = 0.029). Minority-resistant variants were detected in
      21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence
      of minority-resistant variants did not modify baseline viral load and CD4 cell
      count and did not affect the changes in viral load and CD4 cell count.
      CONCLUSION: The transmission of majority-resistant variants, but not minority
      resistant variants, influenced the response to antiretroviral therapy in this
      prospective study. The detection of the transmission of minority-resistant
      variants warrants further clinical validation.

PMID- 18614865
TI  - Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic
      HIV from the plasma of drug-naive individuals.
AB  - OBJECTIVE: HIV-1 utilizes CD4 and either chemokine (C-C motif) receptor 5 (CCR5)
      or chemokine (C-X-C motif) receptor 4 (CXCR4) to gain entry into host cells.
      Small molecule CCR5 antagonists are currently being developed for the treatment
      of HIV-1 infection. Because HIV-1 may also use CXCR4 for entry, the use of CCR5
      entry inhibitors is controversial for patients harboring CCR5-using and CXCR4
      using (dual/mixed-tropic) viruses. The goal of the present study was to determine
      the proportion of CCR5-tropic and CXCR4-tropic viruses in dual/mixed-tropic virus
      isolates from drug-naive patients and the phenotypic and genotypic relationships
      of viruses that use CCR5 or CXCR4 or both. DESIGN: Fourteen antiretroviral-naive
      HIV-1-infected patients were identified as having population coreceptor tropism
      readout of dual/mixed-tropic viruses. Intrapatient comparisons of coreceptor
      tropism and genotype of env clones were conducted on plasma virus from each
      patient. METHODS: Population HIV-1 envelope tropism and susceptibility to the
      CCR5 entry inhibitor, aplaviroc, were performed using the Monogram Biosciences
      Trofile Assay. Twelve env clones from each patient were analyzed for coreceptor
      tropism, aplaviroc sensitivity, genotype, and intrapatient phylogenetic
      relationships. RESULTS: Viral populations from antiretroviral-naive patients with
      dual/mixed-tropic virus are composed primarily of CCR5-tropic env clones mixed
      with those that use both coreceptors (R5X4-tropic) and, occasionally, CXCR4
      tropic env clones. Interestingly, the efficiency of CXCR4 use by R5X4-tropic env
      clones varied with their genetic relationships to CCR5-tropic env clones from the
      same patient. CONCLUSION: These data show that the majority of viruses in these
      dual/mixed-tropic populations use CCR5 and suggest that antiretroviral-naive
      patients may benefit from combination therapy that includes CCR5 entry
      inhibitors.

PMID- 18614866
TI  - Identification of novel markers for liver fibrosis in HIV/hepatitis C virus
      coinfected individuals using genomics-based approach.
AB  - OBJECTIVE: The degree of liver fibrosis is a determinant for initiation of
      therapy for hepatitis C virus. Liver biopsy is invasive, risky and costly, but is
      required to assess fibrosis. This study intended to identify novel noninvasive
      markers to accurately assess fibrosis in HIV/hepatitis C virus coinfection.
      METHODS: Using 100 biopsies from 68 HIV/hepatitis C virus coinfected patients, we
      developed a predictive model consisting of six serum markers along with age and
      antiretroviral therapy experience. DNA microarray analysis of peripheral blood
      mononuclear cells associated with a subset of 51 biopsies obtained from 28
      patients was performed and incorporated into a second model. RESULTS: The eight
      marker model yielded an area under the receiver operating characteristic curve of
      0.904. Combined analysis of clinical and DNA microarray data in the 51-biopsy
      subset identified two genes (alanine amino peptidase-N and mitogen-activated
      protein kinase kinase-3) that predicted fibrosis with high significance. The four
      marker model that included the two genes and two serum markers had an area under
      the receiver operating characteristic curve of 0.852, which did not differ
      significantly from the eight-marker model on this subset (area under the receiver
      operating characteristic curve = 0.856, P = 0.96). CONCLUSION: Both models
      accurately predicted fibrosis with an accuracy of 87.9%, thereby sparing 83% of
      patients from obtaining a biopsy. DNA microarray analysis can be invaluable in
      identifying novel biomarkers of liver fibrosis.

PMID- 18614867
TI  - CD4 deficits and disease course acceleration can be driven by a collapse of the
      CD8 response in rhesus macaques infected with simian immunodeficiency virus.
AB  - OBJECTIVES: Defects in memory CD4+ T cells correlate with development of AIDS in
      monkeys infected with simian immunodeficiency virus, but the early events leading
      to these deficits are unknown. We explored the role of cells specific to simian
      immunodeficiency virus and CD8 cells in the determination of CD4 failure and
      rapid disease course. DESIGN AND METHODS: Using MamuA*01-restricted Gag and Tat
      epitope tetramers, we compared the kinetics of specific response in animals with
      regular (REG) and rapid (RAP) progression. Expressions of memory, activation and
      proliferation markers were examined on the global CD8 pool, as well as on CD4 T
      cells in those animals. In-vivo CD8 depletion in non-MamuA*01 animals was used to
      investigate CD8 collapse as an event leading to disease progression and CD4
      deficits. RESULTS: In animals with a rapid disease course, an initial development
      of cytotoxic T lymphocytes specific to simian immunodeficiency virus is followed
      by collapse accompanied by global changes in CD8 cells and occurs in synchrony
      with the characteristic CD4 deficiencies. Antibody-mediated depletion of CD8
      cells early after infection with simian immunodeficiency virus induces similar
      changes in the CD4 cells and rapid development of AIDS. CONCLUSION: CD8 collapse
      at acute time points may result in uncontrolled viral load and development of a
      defective and insufficient CD4 population. Our results indicate that early
      breakdown in CD8 cells leads to CD4 deficits and rapid progression to AIDS and
      suggest that therapeutic approaches should aim at strengthening CD8 T cells early
      after viral infection.

PMID- 18614868
TI  - Cytomegalovirus and Epstein-Barr virus in breast milk are associated with HIV-1
      shedding but not with mastitis.
AB  - BACKGROUND: Breast milk HIV-1 load is associated with clinical and subclinical
      mastitis, and both milk viral load and mastitis are associated with increased
      mother-to-child-transmission of HIV-1 through breastfeeding. Bacterial infections
      may cause clinical mastitis, but whether other copathogens common in HIV-1
      infection are associated with subclinical mastitis or HIV-1 shedding is unknown.
      DESIGN: A cross-sectional study of HIV-1-infected breastfeeding women in Zimbabwe
      was performed to examine the relationship between a wide range of breast
      coinfections, mastitis, and HIV-1 shedding. METHODS: Breast milk was cultured for
      bacteria and fungi and tested by PCR for mycobacteria, mycoplasmas, human
      herpesvirus (HHV)-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, and HIV-1
      RNA and DNA. Symptoms of clinical mastitis were documented and subclinical
      mastitis was identified by breast milk sodium concentration (Na) and leukocyte
      counts. RESULTS: Coinfections of milk were not associated with clinical or
      subclinical mastitis in the 217 women studied. Detection of HIV-1 RNA, but not
      DNA, in breast milk was associated with cytomegalovirus concentration (odds ratio
      = 1.8, P = 0.002) and detection of Epstein-Barr virus (odds ratio = 3.8, P =
      0.0003) but not other coinfections in multivariate analysis. CONCLUSION:
      Coinfection of breast milk with bacteria, fungi, or herpes viruses was not
      associated with mastitis. The associations between shedding of cytomegalovirus
      and Epstein-Barr virus with HIV-1 in milk suggest a local interaction between
      herpes virus infection and HIV-1 independent of mastitis. Cytomegalovirus and
      Epstein-Barr virus infections may impact HIV-1 shedding in breast milk and the
      risk of MTCT.

PMID- 18614869
TI  - Immune responses that correlate with HIV-1 protection?

PMID- 18614870
TI  - Response to combination antiretroviral therapy: variation by age.
AB  - OBJECTIVE: To provide information on responses to combination antiretroviral
      therapy in children, adolescents and older HIV-infected persons. DESIGN AND
      SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS: : Forty-nine
      thousand nine hundred and twenty-one antiretroviral-naive individuals starting
      combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from
      combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml
      (virological response), CD4 increase of more than 100 cells/microl (immunological
      response) and new AIDS/death were analysed using survival methods. Ten age strata
      were chosen: less than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40
      49, 50-54, 55-59 and 60 years or older; those aged 6 years or more were included
      in multivariable analyses. RESULTS: The four youngest age groups had 223, 184,
      219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613
      individuals. Precombination antiretroviral therapy CD4 cell counts were highest
      in young children and declined with age. By 12 months, 53.7% (95% confidence
      interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and
      immunological response. The probability of virological response was lower in
      those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was
      higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The
      probability of immunological response was higher in children and younger adults
      and reduced in those 60 years or older. Those aged 55-59 and 60 years or older
      had poorer clinical outcomes after adjusting for the latest CD4 cell count.
      CONCLUSION: Better virological responses but poorer immunological responses in
      older individuals, together with low precombination antiretroviral therapy CD4
      cell counts, may place this group at increased clinical risk. The poorer
      virological responses in children may increase the likelihood of emergence of
      resistance.

PMID- 18614871
TI  - HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent
      mother-to-child transmission.
AB  - BACKGROUND: The effects of short-course antiretrovirals given to reduce mother-to
      child transmission (MTCT) on temporal patterns of cell-associated HIV-1 RNA and
      DNA in breast milk are not well defined. METHODS: Women in Kenya received short
      course zidovudine (ZDV), single-dose nevirapine (sdNVP), combination ZDV/sdNVP or
      short-course highly active antiretroviral therapy (HAART). Breast milk samples
      were collected two to three times weekly for 4-6 weeks. HIV-1 DNA was quantified
      by real-time PCR. Cell-free and cell-associated RNA levels were quantified by the
      Gen-Probe HIV-1 viral load assay. RESULTS: Cell-free HIV-1 RNA levels in breast
      milk were significantly suppressed by sdNVP, ZDV/sdNVP or HAART therapy compared
      with ZDV between day 3 and week 4 postpartum (P < or = 0.03). Breast milk HIV-1
      DNA levels (infected cell levels) were not significantly different between
      treatment arms at any timepoint during the 4-6-week follow-up. At 3 weeks
      postpartum, when the difference in cell-free RNA levels was the greatest
      comparing HAART directly with ZDV (P = 0.0001), median log10 HIV-1 DNA copies per
      1 x 10 cells were 2.78, 2.54, 2.69, and 2.31 in the ZDV, sdNVP, ZDV/sdNVP and
      HAART arms, respectively (P = 0.23). Cell-associated HIV-1 RNA levels were
      modestly suppressed in HAART versus ZDV/sdNVP during week 3 (3.37 versus 4.02, P
      = 0.04), as well as over time according to a linear mixed-effects model.
      CONCLUSION: Cell-free and, to a lesser extent, cell-associated HIV-1 RNA levels
      in breast milk were suppressed by antiretroviral regimens used to prevent MTCT.
      However, even with HAART, there was no significant reduction in the reservoir of
      infected cells, which could contribute to breast milk HIV-1 transmission.

PMID- 18614872
TI  - A combined genotype of KIR3DL1 high expressing alleles and HLA-B*57 is associated
      with a reduced risk of HIV infection.
AB  - OBJECTIVES: Coexpression of certain combinations of natural killer cell receptor
      KIR3DL1 and HLA-B alleles is associated with slower time to AIDS. The strongest
      protection in terms of disease outcome in KIR3DL1 homozygotes (3DL1 hmz) is
      coexpression of HLA-B*57 and a set of KIR3DL1 genotypes (3DL1*h/*y) lacking
      alleles expressed at low levels on natural killer cells. We questioned whether
      this allele combination could also influence resistance to infection. DESIGN: The
      genetic distribution of 3DL1*h/*y and HLA-B*57 was compared in 41 HIV-exposed
      uninfected and 186 recently HIV-infected 3DL1 hmz. METHODS: KIR3DL1 subtyping was
      performed by sequencing the exons 3, 4, 5, 7-9. The major histocompatibility
      complex class IB locus was typed by sequence specific oligonucleotide PCR and
      sequencing to resolve Bw4 and Bw6 alleles and the amino acid present at position
      80. RESULTS: Percentage carriers of HLA-B*57 in HIV-exposed uninfected and
      individuals in a primary infection cohort was 12.2 and 4.3%, respectively (P =
      0.0631), whereas that of 3DL1*h/*y was similar in both populations (P = 0.221).
      The 3DL1*h/*y-HLA-B*57 combined genotype was more frequent in exposed uninfected
      individuals (12.2%) than individuals in primary infection (2.7%) (P = 0.019; odds
      ratio, 5.03; 95% confidence intervals, 1.38-18.3). CONCLUSION: Coexpression of
      3DL1*h/*y and B*57, which has been associated with a reduced risk of progressing
      to AIDS in HIV-infected individuals also lowers the risk of HIV infection in
      exposed uninfected individuals.

PMID- 18614873
TI  - Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies.
AB  - OBJECTIVES: To assess and summarize the published literature on the extent to
      which bacterial vaginosis may increase the risk of HIV acquisition. DESIGN: Meta
      analysis of published studies. METHODS: Medline and other electronic databases
      were systematically searched for eligible publications. The association between
      bacterial vaginosis and incident HIV was separately analyzed from that between
      bacterial vaginosis and prevalent HIV. The latter was further analyzed,
      stratified by bacterial vaginosis diagnostic method, HIV risk profile of the
      study population, and whether or not adjusted estimates were presented. RESULTS:
      Twenty-three eligible publications were identified, including a total of 30,739
      women. Bacterial vaginosis was associated with an increased risk of HIV
      acquisition in HIV-incidence studies (relative risk = 1.6, 95% confidence
      interval: 1.2, 2.1). All but one of 21 HIV-prevalence studies reported estimates
      above the null. The latter results were heterogeneous and showed some evidence of
      funnel plot asymmetry, precluding the estimation of a single summary measure. The
      association between bacterial vaginosis and HIV in prevalence studies appeared
      stronger for women without high-risk sexual behavior. CONCLUSION: Bacterial
      vaginosis was consistently associated with an increased risk of HIV infection.
      High bacterial vaginosis prevalence may result in a high number of HIV infections
      being attributable to bacterial vaginosis. More prospective studies are needed to
      accurately evaluate the role of bacterial vaginosis in HIV acquisition in low
      risk versus high-risk women. Furthermore, randomized clinical trials may be worth
      considering to determine the effect of bacterial vaginosis control measures on
      HIV acquisition.

PMID- 18614875
TI  - Serum alpha-fetoprotein predicts virologic response to hepatitis C treatment in
      HIV coinfected patients.
AB  - We explored the link between serum alpha-fetoprotein levels and virologic
      response in 383 HIV-hepatitis C virus coinfected patients. A low alpha
      fetoprotein level (<5.0 ng/ml) was an independent predictor of sustained
      virologic response (odds ratio = 1.83; 95% confidence interval 1.05-3.20). Serum
      alpha-fetoprotein measurement should be integrated in the pretreatment assessment
      of prognostic factors of a virologic response.

PMID- 18614876
TI  - Single-nucleotide polymorphisms in human beta-defensin-1 gene in Mozambican HIV-1
      infected women and correlation with virologic parameters.
AB  - We analyzed single nucleotide polymorphisms in the 5'-untranslated region (-44C/G
      and -52G/A) of the beta-defensin-1 gene in 78 Mozambican HIV-1-infected mothers.
      We observed significantly lower levels of HIV-1 RNA in breast milk, but not in
      plasma, in women with the -52GG genotype versus women with the -52GA and -52AA
      genotypes, supporting the hypothesis that different expression of beta-defensins
      could have an impact on viral replication in breast milk.

PMID- 18614874
TI  - Prevention of mother-to-child HIV transmission: similar access for sub-Sahara
      African immigrants and for French women?
AB  - OBJECTIVE: : To investigate whether mother-to-child transmission (MTCT)
      management and rate differed between African immigrants and French-born women
      delivering in France. METHODS: : MTCT strategies were studied among human
      immunodeficiency virus type 1-infected women delivering between 1984 and 2007 in
      the multicenter French Perinatal Cohort, according to geographical origin.
      RESULTS: : Among 9245 pregnancies (in 7090 women), the proportion of African
      mothers increased from 12% in 1984-1986 to 64% in 2003-2004. African women had
      later access to care than French women, even in recent years (1997-2004). They
      more often discovered their HIV infection during pregnancy (40.6 vs. 11.5%, P <
      0.001), started prenatal care in the third trimester (14.1 vs. 9.8%, P < 0.001)
      and started antiretroviral therapy after 32 weeks gestation (7.6 vs. 4.1%, P <
      0.001). The association with late treatment initiation disappeared when adjusted
      for late HIV diagnosis and prenatal care (adjusted odds ratio 1.0, 95% confidence
      interval 0.7-1.4). African and French women did not differ in terms of access to
      highly active antiretroviral therapy, nor for substandard management such as
      vaginal delivery with uncontrolled viral load, lack of intrapartum and postpartum
      treatment or breastfeeding. The MTCT rate was higher for African than for French
      women receiving antiretroviral therapy (1.8 vs. 0.8%, P = 0.02), but the
      difference was no longer significant after adjustment for main transmission risk
      factors (adjusted odds ratio = 1.7, 95% confidence interval 0.8-3.7, P = 0.17).
      MTCT did not differ among 2110 term deliveries with maternal viral load less than
      400 copies/ml, (0.8 vs. 0.6%, P = 0.5). CONCLUSION: : African immigrants more
      often had late HIV screening in pregnancy than French-born women, but had similar
      access to MTCT prevention, once the infection was diagnosed.

PMID- 18614877
TI  - Significant differences in DNA viral load between HIV-1 and HIV-2 infected
      patients.

PMID- 18614878
TI  - An unusual abacavir reaction.

PMID- 18614879
TI  - Severe abacavir hypersensitivity reaction in a patient tested HLA-B*5701
      negative.

PMID- 18614880
TI  - Fatal disseminated toxoplasmosis with congenital transmission in an African
      migrant.

PMID- 18614881
TI  - Mononucleosis and athletic participation: an evidence-based subject review.
AB  - Infectious mononucleosis (IM) is a common medical condition that afflicts
      thousands of young athletes each year. Despite the self-limited nature of this
      disorder, the variability of the clinical presentation and the rare risk of
      splenic rupture routinely present sports medicine clinicians with difficult
      return-to-play decisions. Currently there are no evidence-based guidelines
      regarding the management of the athlete with IM. This review discusses the
      available research data pertaining to the management of IM in young athletes and
      develops questions for future clinical research.

PMID- 18614882
TI  - Biomechanical analysis of football neck collars.
AB  - OBJECTIVE: To determine the load-limiting capabilities of protective neck collars
      used in football through dynamic impact testing. DESIGN: A 50th-percentile male
      Hybrid III dummy was used in 48 dynamic impact tests comparing The Cowboy Collar,
      Bullock Collar, and Kerr Collar. A control and each collar were tested at two
      velocities (5 m/s and 7 m/s), three impact locations (front, top, and side of the
      helmet), and two shoulder pad positions (normal and raised). SETTING: Research
      laboratory. PATIENTS: None. INTERVENTIONS: None. Independent variables were the
      neck collars, impact velocity, and shoulder pad position. MAIN OUTCOME
      MEASUREMENTS: In addition to range of motion, upper and lower neck forces and
      moments were measured. RESULTS: With the top impact location, it was found that
      the Kerr Collar and Bullock Collar reduced head accelerations and force
      transmission through the neck. With the front impact location, all the collars
      reduced lower neck moment. The Kerr Collar was also capable of reducing the lower
      neck force and upper neck moment. With the side impact location, the Kerr Collar
      substantially reduced lower neck moment. CONCLUSIONS: These reductions in loads
      correlate with the degree to which each collar restricted the motion of the head
      and neck. By restricting the range of motion of the neck and redistributing load
      to the shoulders, neck loads can be effectively lowered.

PMID- 18614883
TI  - Does the apolipoprotein epsilon 4 allele predispose varsity athletes to
      concussion? A prospective cohort study.
AB  - OBJECTIVE: To determine the association between the apolipoprotein epsilon 4
      allele and concussion. We hypothesized that apolipoprotein epsilon 4 carriers may
      be more likely to sustain a concussion. DESIGN: Prospective cohort study.
      SETTING: University of Toronto varsity athletics. PARTICIPANTS: Included 318 of
      822 collegiate student athletes who participated in University of Toronto varsity
      sports from September 2002 to April 2006. ASSESSMENT OF RISK FACTORS: The
      presence of apolipoprotein epsilon 4 was described dichotomously after genotyping
      blood samples collected from participants. MAIN OUTCOME MEASUREMENTS: Concussions
      were identified by sport-medicine professionals present on the sidelines using on
      field assessment forms. All concussion diagnoses were verified by a sports
      medicine physician. Survival analysis was used to determine the association
      between apolipoprotein epsilon 4 and first concussion. RESULTS: The unadjusted
      hazard ratio for concussion in the apolipoprotein epsilon 4 carriers was 1.18
      (95% CI: 0.52, 2.69) compared to noncarriers. Adjustment for sex, weight, height,
      and team type resulted in a hazard ratio of 1.06 (95% CI: 0.41, 2.72), indicating
      little effect from confounding factors. CONCLUSIONS: There is no important
      association between carrying the apolipoprotein epsilon 4 allele and sustaining a
      concussion. At this time, we do not recommend preseason genetic testing for
      varsity athletes as a mechanism for targeting prevention strategies.

PMID- 18614884
TI  - The effects of neuromuscular training on knee joint motor control during
      sidecutting in female elite soccer and handball players.
AB  - OBJECTIVE: The project aimed to implement neuromuscular training during a full
      soccer and handball league season and to experimentally analyze the neuromuscular
      adaptation mechanisms elicited by this training during a standardized sidecutting
      maneuver known to be associated with non-contact anterior cruciate ligament (ACL)
      injury. DESIGN: The players were tested before and after 1 season without
      implementation of the prophylactic training and subsequently before and after a
      full season with the implementation of prophylactic training. PARTICIPANTS: A
      total of 12 female elite soccer players and 8 female elite team handball players
      aged 26 +/- 3 years at the start of the study. INTERVENTION: The subjects
      participated in a specific neuromuscular training program previously shown to
      reduce non-contact ACL injury. METHODS: Neuromuscular activity at the knee joint,
      joint angles at the hip and knee, and ground reaction forces were recorded during
      a sidecutting maneuver. Neuromuscular activity in the prelanding phase was
      obtained 10 and 50 ms before foot strike on a force plate and at 10 and 50 ms
      after foot strike on a force plate. RESULTS: Neuromuscular training markedly
      increased before activity and landing activity electromyography (EMG) of the
      semitendinosus (P < 0.05), while quadriceps EMG activity remained unchanged.
      CONCLUSIONS: Neuromuscular training increased EMG activity for the medial
      hamstring muscles, thereby decreasing the risk of dynamic valgus. This observed
      neuromuscular adaptation during sidecutting could potentially reduce the risk for
      non-contact ACL injury.

PMID- 18614885
TI  - Short- and long-term influences of a custom foot orthotic intervention on lower
      extremity dynamics.
AB  - OBJECTIVE: The objective of the current study was to analyze the influence of a
      short-term and long-term custom foot orthotic (CFO) intervention on the lower
      extremity dynamics in a group of female runners with a history of overuse running
      knee injury. DESIGN: Descriptive laboratory study. SETTING: University of
      Massachusetts Biomechanics Laboratory, Amherst, MA. PARTICIPANTS: This study
      included a group of female recreational runners (15 to 40 km per week) who had a
      history of overuse running knee injury in the 6 months leading up to the study.
      INTERVENTION: Semi-rigid, custom foot orthoses manufactured from a neutral
      suspension cast and designed to meet the specific needs of each subject. Subjects
      wore the custom foot orthoses during all running activities for a period of 6
      weeks. MAIN OUTCOME MEASURES: Three-dimensional ankle and knee dynamics were
      collected while subjects performed over-ground running trials with and without a
      CFO intervention. Data were collected before and after a 6-week CFO intervention
      during all running activities. RESULTS: For ankle parameters, short-term
      intervention led to significant decreases in maximum values for rearfoot eversion
      angle and velocity, impact peak, and loading rate. Ankle inversion impulse was
      also significantly decreased during the loading phase. At the knee, maximum knee
      external rotation moment was significantly increased when subjects wore the
      custom foot orthoses. CONCLUSIONS: The 6-week intervention led to subjective
      changes, including a significant decrease in pain. An improvement in symptoms did
      occur with the 6-week intervention. In addition, dynamic results revealed that
      custom foot orthoses have an immediate effect on dynamics and that this influence
      occurs only when orthoses are worn in the footwear. The short-term CFO
      intervention led to significant decreases in rearfoot kinematics (maximum
      eversion angle and velocity) but no changes observed in knee kinematics. The
      kinetic analysis revealed that these subjects exhibited significant decreases in
      maxima for ankle inversion moment and angular impulse during the loading phase,
      impact peak, and vertical loading rate with short-term, CFO intervention. At the
      knee, the CFO condition led to increases in knee external rotation moment maxima
      and angular impulse.

PMID- 18614886
TI  - Hyponatremia among runners in the Zurich Marathon.
AB  - OBJECTIVE: Hyperhydration and exercise-associated hyponatremia (EAH) are critical
      issues during endurance events. We studied a cohort of marathon runners to
      examine EAH's prevalence in a marathon with a short time limit and to investigate
      underlying mechanisms that may be responsible for its development. DESIGN:
      Observational cohort study. SETTING: 2006 Zurich Marathon (cool and rainy
      weather, time limit of 5 hours). PARTICIPANTS: 167 marathon runners were
      recruited the month before the race. MAIN OUTCOME MEASURES: Body mass, plasma
      sodium, and osmolality were measured just before the start and immediately after
      the race. Fluid intake during the race was ascertained by a recall questionnaire.
      RESULTS: Five subjects (3 %) developed asymptomatic EAH, and no symptomatic EAH
      was found. Body mass change during the race correlated similarly with postrace
      sodium levels (r = -0.72, P < 0.0001) and with sodium change during the race (r =
      -0.66, P < 0.0001). Postrace sodium levels correlated significantly with sodium
      change during the race (r = 0.74, P < 0.0001). Fluid intake correlated
      significantly (r = -0.43, P < 0.0001) with plasma sodium change between the start
      and finish of the race. Postrace sodium levels and postrace osmolality were
      significantly correlated (r = 0.68, P < 0.0001). CONCLUSION: In this study we
      observed a relatively low incidence of EAH in subjects running the marathon in
      around 2.5 to 5 hours and in a cool environment. Plasma sodium change during the
      race and postrace sodium levels correlated with body mass change. There was also
      a direct correlation between fluid intake and plasma sodium change during the
      race.

PMID- 18614887
TI  - Practical management of exercise-associated hyponatremic encephalopathy: the
      sodium paradox of non-osmotic vasopressin secretion.
AB  - Exercise-associated hyponatremia (EAH) is a potentially fatal fluid imbalance
      largely resulting from sustained fluid intake beyond the capacity for fluid
      excretion during endurance exercise. Common symptoms include vomiting, confusion,
      altered mental status, and seizures; however, these symptoms can also be seen
      with hypernatremic encephalopathy, making measurement of plasma sodium
      concentration imperative when athletes present with these symptoms. Recent
      evidence supports the inappropriate secretion of the antidiuretic hormone,
      arginine vasopressin (AVP), as the primary pathophysiological mechanism
      underlying the development of dilutional EAH. It appears that AVP is stimulated
      normally during prolonged endurance running by non-osmotic factors such as an
      exercise-induced plasma volume decrease; therefore, any excess fluid intake will
      likely be retained, and sodium will likely be excreted. The capacity for a small
      concentrated bolus of a hypertonic saline solution to rapidly reverse cerebral
      edema and remove any decreased plasma volume stimulus to AVP secretion is the
      most efficacious treatment for acute EAH encephalopathy to date. The prompt
      administration of an intravenous (IV) bolus of hypertonic saline in the field or
      hospital setting can be lifesaving once EAH is documented. Conversely, oral
      sodium supplementation will not prevent the development of EAH encephalopathy if
      exuberant fluid intake combined with non-osmotic secretion of AVP occurs during
      prolonged physical activity. As a result, the seemingly paradoxical use of sodium
      supplementation as the most effective practical management therapy (IV bolus) and
      ineffective preventive strategy can be reconciled through a more complete
      understanding of the pathophysiological mechanisms underlying EAH.

PMID- 18614888
TI  - Effects of modern ski equipment on the overall injury rate and the pattern of
      injury location in Alpine skiing.
AB  - OBJECTIVE: To identify whether the introduction of carving skis and related
      equipment has altered the overall injury rate and/or the pattern of injury
      location. DESIGN: Comparative case series. SETTING: In the winter season of 1997
      98, when carving skis began to appear on the ski market, all injured skiers
      requiring evacuation or medical treatment in 70 Austrian ski areas were recorded.
      Five years later, when most skiers were using carving skis, ski injury data were
      collected in a representative sample consisting of 5 ski areas from the first
      study. ASSESSMENT OF RISK FACTORS: Data collection on injured skiers included
      subject demographics, weather and snow conditions, mechanism of the skiing
      accident, the type of ski used, injury location, and in the second study,
      additionally the date of the last ski binding adjustment. MAIN OUTCOME
      MEASUREMENTS: Frequency of injured body parts. RESULTS: In 1997-98, 1.43 injuries
      per 1000 skier days were calculated. Out of 17,914 injured alpine skiers, 29.5%
      of the injured men and 53.0% of the injured women suffered knee injuries. Five
      years later with the introduction of carving skis, the overall injury rate
      decreased by 9% but the gender-specific percentages of knee injuries did not
      change. Female carving skiers not using newly adjusted bindings had a higher risk
      of knee injury than those with newly adjusted bindings. CONCLUSION: The
      maintenance of adequate binding adjustment is especially important for the
      prevention of knee injuries in female carving skiers.

PMID- 18614889
TI  - MRI-demonstrated outcome of subchondral stress fractures of the knee after
      treatment with iloprost or tramadol: observations in 14 patients.
AB  - OBJECTIVE: To investigate the outcome of subchondral stress fractures (SSF) of
      the knee after treatment with the prostacyclin analogue Iloprost or the opioid
      analgesic Tramadol. DESIGN: Case series/retrospective review. SETTING: Tertiary
      care center. PATIENTS: Fourteen patients with at least a single subchondral
      stress fracture of the knee, surrounded by bone marrow edema, visible on T1
      weighted and short tau inversion recovery magnetic resonance images.
      INTERVENTIONS: Nine patients had been treated with oral Iloprost (group 1; 11
      SSF) and 5 patients with Tramadol (group 2; 5 SSF) for 4 weeks in the course of a
      double-blind, randomized clinical trial. MR images were obtained at baseline (1
      day before the start of treatment), after 3 months, and after 1 year. MAIN
      OUTCOME VARIABLES: SSF volumes and their rates of change between baseline and
      follow-up examinations, as determined on T1-weighted images by computer-assisted
      quantification. RESULTS: After three months, the SSF volumes had decreased by a
      median of 42.2% in group 1 and increased by a median of 2.2% in group 2 (P =
      0.008). After 1 year, the median decrease in SSF volumes was 100.0% in group 1
      and 65.7% in group 2 (P = 0.017). CONCLUSION: This small case series suggests
      that healing of SSF is more pronounced after Iloprost treatment.

PMID- 18614890
TI  - Aerobic exercise with relaxation: influence on pain and psychological well-being
      in female migraine patients.
AB  - OBJECTIVE: The objective of this pilot study was to address the influence of an
      aerobic exercise program combined with relaxation on pain and psychological
      variables in migraine patients. DESIGN: Controlled, randomised design with half
      of the group receiving an intervention (aerobic exercise group) in addition to
      standard medical care received by all patients. SETTING/PATIENTS/OUTCOME
      MEASUREMENT: Thirty female migraine outpatients completed a range of
      psychological questionnaires measuring sensational and affective dimensions of
      pain, body image, depression, and quality of life. INTERVENTION: The aerobic
      exercise group (n = 15) participated in a 6-week, twice-weekly, indoor exercise
      program (45 minutes of gymnastics with music and 15 minutes of progressive muscle
      relaxation). RESULTS/CONCLUSION: The program led to a significant reduction of
      self-rated migraine pain intensity. Although there was an improvement in
      depression-related symptoms within the aerobic exercise group, no significant
      differences in psychological variables between groups were found.

PMID- 18614891
TI  - Exertional rhabdomyolysis in seven division-1 swimming athletes.

PMID- 18614892
TI  - The diagnosis and management of psoriatic arthritis in a professional football
      player presenting with a knee effusion: a case report.

PMID- 18614893
TI  - Complex strain injury involving an intercostal hematoma in a professional
      baseball player.

PMID- 18614894
TI  - Early determinants of physical activity levels in children.

PMID- 18614895
TI  - Is physical activity protective against functional impairment in later life in
      obese as well as normal weight persons?

PMID- 18614896
TI  - Immobilization versus functional treatment for ankle sprains: a systematic
      review.

PMID- 18614897
TI  - MRI vs clinical examination for diagnosing meniscus tears: a review.

PMID- 18614899
TI  - Is there a role for sodium bicarbonate in treating lactic acidosis from shock?
AB  - PURPOSE OF REVIEW: Bicarbonate therapy for severe lactic acidosis remains a
      controversial therapy. RECENT FINDINGS: The most recent 2008 Surviving Sepsis
      guidelines strongly recommend against the use of bicarbonate in patients with pH
      at least 7.15, while deferring judgment in more severe acidemia. We review the
      mechanisms causing lactic acidosis in the critically ill and the scientific
      rationale behind treatment with bicarbonate. SUMMARY: There is little rationale
      or evidence for the use of bicarbonate therapy for lactic acidosis due to shock.
      We agree with the Surviving Sepsis guidelines recommendation against the use of
      bicarbonate for lactic acidosis for pH at least 7.15 and we further recommend a
      lower target pH of 7.00 or less. If bicarbonate is used, consideration must be
      given to slow infusion and a plan for clearing the CO2 that is produced and
      measuring and correcting ionized calcium as the resultant 10% drop may decrease
      cardiac and vascular contractility and responsiveness to catecholamines. When
      continuous renal replacement therapy is used during severe acidosis, we recommend
      bicarbonate-based replacement fluid over citrate as citrate may increase the
      strong ion gap. Effective therapy of lactic acidosis due to shock is to reverse
      the cause.

PMID- 18614900
TI  - Should we abandon corticosteroids during septic shock? No.
AB  - PURPOSE OF REVIEW: With the publication of the results of the recent CORTICUS
      trial, stress ('low') doses of corticosteroids for the treatment of vasopressor
      dependent septic shock in adults can still be considered controversial. The
      purpose of this narrative review is to elaborate the pros and cons of this
      treatment in clinical practice and to formulate clinical and research directions.
      RECENT FINDINGS: The recent CORTICUS study only shows a beneficial effect of
      stress doses of corticosteroids in the time interval to shock reversal and not on
      mortality, potentially explained by an increased risk for superinfection. The
      mortality in the placebo arm was relatively low and lower than in earlier
      randomized studies in which stress doses of corticosteroids had a favorable
      hemodynamic effect and conferred a survival benefit in septic shock. SUMMARY:
      Treatment by stress doses of corticosteroids should not be abandoned during
      septic shock. Additional studies are needed, however, to better delineate the
      patient group with the highest likelihood to benefit from this therapy, as a
      function of severity of illness, response to adrenocorticotrophic hormone testing
      or both. For now, results of the CORTICUS study should not change current
      clinical practice of administering 200-300 mg of hydrocortisone daily (in divided
      doses) in case of fluid and vasopressor-insensitive septic shock and rapid
      tapering of this treatment on the basis of a hemodynamic response.

PMID- 18614901
TI  - Better outcomes through continuous infusion of time-dependent antibiotics to
      critically ill patients?
AB  - PURPOSE OF REVIEW: Increasing interest is being directed toward possible benefits
      associated with continuous infusion of time-dependent antibiotics such as beta
      lactams and vancomycin to critically ill patients. The background, emerging
      evidence and practical considerations associated with continuous infusions are
      discussed. RECENT FINDINGS: One large retrospective cohort study has found
      clinical outcome benefits of administering a beta-lactam antibiotic by extended
      infusion compared with bolus administration. This complements a smaller
      randomized controlled trial comparing continuous infusion and intermittent bolus
      administration. For vancomycin, clinical outcome benefits have only been shown in
      a ventilator-associated pneumonia cohort of critically ill patients. No clinical
      outcome studies have been conducted for other time-dependent antibiotics.
      SUMMARY: Continuous infusion of vancomycin and beta-lactam antibiotics enables
      faster and more consistent attainment of therapeutic levels compared with
      intermittent bolus dosing. Although the clinical benefits have not been
      conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic
      support for continuous infusion nevertheless exists. Given that critically ill
      patients may develop very large volumes of distribution as well as supranormal
      drug clearances, individualized therapy through the use of therapeutic drug
      monitoring is required. A definitive determination of the relative clinical
      efficacy of intermittent bolus and continuous administration of beta-lactams or
      vancomycin will only be achieved after a large-scale multicenter randomized
      controlled trial has been performed.

PMID- 18614902
TI  - Hypoglycemia and strict glycemic control in critically ill patients.
AB  - PURPOSE OF REVIEW: In contrast to patients with diabetes mellitus, data on
      consequences of hypoglycemia in critically ill patients are sparse. The purpose
      of this review is to summarize available data on prevalence of hypoglycemia, risk
      factors, and possible consequences of hypoglycemia in critically ill patients.
      RECENT FINDINGS: There is strong evidence that strict glycemic control is
      beneficial for critically ill patients. Recent attempts to confirm these findings
      have not succeeded. Instead, they have increased the fear for negative
      consequences of hypoglycemia. Hypoglycemia is four to seven times more frequent
      in patients treated with strict glycemic control. Risk factors for hypoglycemia
      are a change in nutrition without adjustment of insulin treatment, diabetes
      mellitus, sepsis, shock, liver failure, and the need for renal replacement
      therapy. Consequences of hypoglycemia in critically ill patients are not well
      defined, but overall current evidence suggests that beneficial effects of strict
      glycemic control outweigh possible negative effects of hypoglycemia. SUMMARY:
      Hypoglycemia should be avoided in critically ill patients, but not at the cost of
      less stringent glycemic control. Strict glycemic control with a low incidence of
      hypoglycemia can be achieved with a validated (computerized) algorithm and
      increased surveillance in patients with an increased risk for hypoglycemia.

PMID- 18614903
TI  - The pharmacology of oversedation in mechanically ventilated adults.
AB  - PURPOSE OF REVIEW: To review pharmacological-related factors that affect the
      incidence of oversedation in mechanically ventilated adults. RECENT FINDINGS:
      Recent epidemiologic studies have identified a high frequency of oversedation in
      the ICU that is attributable, in part, to a number of pharmacokinetic,
      pharmacogenetic, and pharmacodynamic factors. New evidence suggests that the
      administration of benzodiazepines, even when dosed intermittently, will lead to
      more oversedation than either propofol or dexmedetomidine and is associated with
      greater healthcare costs. Based on this data, clinicians should limit the use of
      benzodiazepines to those patients with anxiety, seizures, alcohol withdrawal, or
      in whom a deeper level of sedation or therapeutic paralysis is required. SUMMARY:
      Recognition of these new advances will help liberate patients from mechanical
      ventilation sooner, without compromising patient comfort.

PMID- 18614904
TI  - Enteral vs. parenteral nutrition for the critically ill patient: a combined
      support should be preferred.
AB  - PURPOSE OF REVIEW: Current recommendations suggest starting enteral feeding as
      soon as possible whenever the gastrointestinal tract is functioning. The
      disadvantage of enteral support is that insufficient energy and protein coverage
      can occur. This review focuses on some recent findings regarding the nutritional
      support of critically ill patients and evaluates the data presented. RECENT
      FINDINGS: An increasing nutritional deficit during a long ICU stay is associated
      with increased morbidity (infection rate, wound healing, mechanical ventilation,
      length of stay, duration of recovery), and costs. Evidence shows that enteral
      nutrition can result in underfeeding and that nutritional goals are frequently
      reached only after 1 week. Contrary to former beliefs, recent meta-analyses of
      ICU studies showed that parenteral nutrition is not related to a surplus
      mortality and may even be associated with improved survival. SUMMARY: Early
      enteral nutrition is recommended for critically ill patients. Supplemental
      parenteral nutrition combined with enteral nutrition can be considered to cover
      the energy and protein targets when enteral nutrition alone fails to achieve the
      caloric goal. Whether such a combined nutritional support provides additional
      benefit on the overall outcome has to be proven in further studies on clinical
      outcome, including physical and cognitive functioning, quality of life, cost
      effectiveness, and cost-utility.

PMID- 18614905
TI  - Ultrasound in the surgical intensive care unit.
AB  - PURPOSE OF REVIEW: Critically ill patients are subjected to a variety of
      diagnostic and therapeutic procedures. It is desirable to make these
      interventions as timely, safe, and effective as possible. Bedside ultrasound and
      echocardiography are tools that allow for diagnosis of many conditions, without
      subjecting the patient to radiation, dye, and the risks of transport. In
      addition, ultrasound guidance of procedures may improve safety and efficacy. This
      review analyzes the literature on ultrasound and echocardiography use in the ICU.
      RECENT FINDINGS: There is evidence supporting the use of bedside echocardiography
      and ultrasound for the diagnosis of chest, abdominal, and other pathologic
      conditions in the ICU. There is also evidence to support ultrasound guidance of
      vascular access and other procedures. There are multiple reports of novel uses of
      bedside echocardiography and ultrasound in the ICU. SUMMARY: There is substantial
      literature supporting ultrasound and bedside limited echocardiography in the
      critical care setting. In addition, there are frequent reports of new
      applications for these technologies in the literature. The role of ultrasound and
      bedside limited echocardiography in the critical care setting is likely to expand
      in the future and become a part of daily care in every surgical intensive care
      unit.

PMID- 18614906
TI  - When is faster better? Operative timing in acute care surgery.
AB  - PURPOSE OF REVIEW: Evaluation and treatment of the acute abdomen is the expertise
      of the general surgeon. Still, early and accurate diagnosis of this condition
      remains a dilemma and is particularly challenging in critically ill patients.
      This review examines recent literature regarding optimal timing of operation for
      common acute gastrointestinal conditions. RECENT FINDINGS: No conclusive evidence
      exists to guide surgeons in the decision of when to operate on common
      gastrointestinal problems. Recent data support changes in traditional views of
      treating these conditions: the debate surrounding emergent appendectomy for acute
      appendicitis is more active than ever, but interval appendectomy appears to be
      unnecessary in asymptomatic patients, laparoscopic cholecystectomy for acute
      cholecystitis is safe, regardless of the duration of symptoms; sigmoid colectomy
      for acute diverticulitis is no longer required after two episodes; and surgeon
      experience with developing diagnostic and therapeutic technologies continues to
      evolve. SUMMARY: A combination of physical findings, laboratory data, and
      directed imaging studies help establish a diagnosis and predict the benefit of
      surgical intervention in common acute abdominal problems. Advanced imaging
      technology and critical care support have facilitated changes in operative timing
      in acute care surgery.

PMID- 18614907
TI  - Prevention and treatment of pressure ulcers in the surgical intensive care unit.
AB  - PURPOSE OF REVIEW: To review recent work on pressure ulcer prevention and
      treatment in the intensive care unit within the context of previous work. RECENT
      FINDINGS: Although pressure ulcerations are an age-old and relatively common
      problem, their pathophysiology, risk factors for their development, and treatment
      options lack complete understanding. Most of the available literature is based on
      noncritical care patient clinical experience in noncritical care journals.
      Previous estimates of pressure ulcer underestimate the problem in high-acuity
      intensive care units. Available risk factors in previously validated tools may
      not be accurate in the intensive care unit patient population. However, the
      current literature provides an initial footing for intensivists to improve their
      pressure ulcer prevention and treatment methods that will become increasingly
      important for clinical certification as well as research. SUMMARY: Preventing and
      treating pressure ulcers will continue to be a troublesome problem for
      intensivists. Accurate assessments and comparisons remain problematic across a
      heterogeneous intensive care unit population. Risk stratification schema need
      tailoring to the problems of intensive care unit patients. Treatment modalities
      may not prevent all pressure ulcer development or extension. Available data
      support dedicated training of nurses and physicians to maximize local intensive
      care unit resources to minimize the impact of pressure ulceration.

PMID- 18614908
TI  - Feeding the injured intestine: enteral nutrition in the critically ill patient.
AB  - PURPOSE OF REVIEW: The utilization of enteral nutrition in critically ill
      patients is frequently suboptimal. This may be due, in part, to ongoing
      controversies regarding appropriate use of enteral support, but there are also
      perceived barriers to its use even when there is good evidence that it can be
      given. This review was undertaken to outline some of these controversies and
      barriers to use of enteral nutrition in the ICU. RECENT FINDINGS: Although the
      advantages of enteral nutrition may have been overstated, it remains preferable
      to parenteral nutrition for support of critically ill patients. Early initiation
      of enteral support is a reasonable approach. Many patients with perceived
      contraindications to enteral therapy are actually good candidates for its use.
      Frequent interruptions in enteral nutrition lead to suboptimal nutrient delivery,
      but might be overcome by use of specific protocols emphasizing safe and effective
      utilization of enteral support. SUMMARY: Use of enteral nutritional support is
      recommended for critically ill patients requiring specialized nutritional
      support. Barriers to its use could be overcome by better educating providers
      about indications for use and by developing methods to avoid undue interruption
      of therapy.

PMID- 18614909
TI  - Is there a role for growth hormone therapy in refractory critical illness?
AB  - PURPOSE OF REVIEW: Protein catabolism is common among critically ill patients,
      contributing to organ dysfunction, muscle weakness, prolonged mechanical
      ventilation and length of stay in the ICU, with adverse impact on patient
      prognosis and resource utilization. Neither adequate enteral nutrition nor
      parenteral nutrition stems this catabolism. Recombinant growth hormone
      supplementation in surgical trauma and burn injury patients has demonstrated
      nitrogen retention, increased insulin-like growth factor-1 levels, decreased
      length of stay and improved survival. As a result, growth hormone became widely
      used in the ICU, until two large randomized trials in 1999 noted increased
      mortality associated with infection and organ dysfunction. RECENT FINDINGS: Small
      clinical trials have revisited growth hormone supplementation in prolonged
      critical illness, demonstrating nitrogen conservation and increased serum levels
      of insulin-like growth factor-1 and insulin-like growth factor-1 binding protein
      in patients receiving adequate nutrition support. These trials suggest growth
      hormone supplementation may be safe and more efficacious in a subclass of chronic
      critically ill patients. SUMMARY: Prior to proposing new prospective randomized
      clinical trials, case reports describing anecdotal experience with growth hormone
      in selected chronically critically ill patients may provide insight into
      redefining the ICU population most likely to benefit from growth hormone
      supplementation. Current guidelines continue to recommend against the use of
      growth hormone in critical illness.

PMID- 18614910
TI  - Trauma rehabilitation outcome scoring.
AB  - PURPOSE OF REVIEW: Appropriate measurements of success in trauma systems are
      evolving. We review the rationale behind prior trauma and rehabilitation outcomes
      measures, and how they have led to the current rehabilitation tools in use today.
      In addition, we review the difficulties with current methods and future
      improvements that need to occur. RECENT FINDINGS: As medicine marches toward
      improved used of clinical evidence, trauma practitioners have worked for improved
      outcomes research. A major part of this is that outcomes such as functional
      status and quality of life are as important as mortality statistics. Trauma
      rehabilitation outcomes are thus more important, yet in the past all such tools
      have had major impediments to implementation across a heterogeneous trauma
      population. Newly recognized major domains such as quality of life, preinjury
      status, patient perceptions, and actual function at work have not been adequately
      addressed with current rehabilitation measures. At this time, no clinically
      applicable trauma rehabilitation score exists. SUMMARY: Trauma rehabilitation
      outcomes are an important measurement of trauma system effectiveness. A more
      effective, easily applied rehabilitation score is needed to adequately assess all
      appropriate domains of clinical improvement in the injured patient.

PMID- 18614911
TI  - From rehabilitation to optimal function: role of clinical exercise therapy.
AB  - PURPOSE OF REVIEW: Increasing numbers of critically ill and injured patients are
      surviving their initial hospitalization. The immobilization associated with long
      term critical care can lead to deterioration of the musculoskeletal system within
      6 h of bed rest, and muscle strength can decline by as much as 40% within a week
      of immobilization. RECENT FINDINGS: The physical, emotional, and social deficits
      consequent to immobilization persist despite current rehabilitation, and a
      substandard quality of life following the event ensues for as long as 7 years
      post-trauma. The cause of decline in quality of life is believed to stem most
      directly from the physical impact of illness, resulting in such impairments as
      weakness, fatigue, and difficulty in mobilization. SUMMARY: Physical therapy is a
      necessary component of the rehabilitation process. Although physical therapy
      often succeeds in restoration of the activities of daily life, patients are often
      unequipped to resume their pretrauma level of activity or functional capacity,
      including return to work or school. We opine that a vigorous program of physical
      training implemented soon after discharge from physical therapy is a logical and
      cost-effective extension of the continuum of rehabilitation after critical
      illness. Such extension, supervised by an advanced exercise specialist, addresses
      many physical limitations that persist after critical illness and limit
      functional recovery.

PMID- 18614912
TI  - New perspectives on error in critical care.
AB  - PURPOSE OF REVIEW: Despite unprecedented attention on the issue of medical error
      over the last 8 years, there is little evidence of widely available improvements
      in patient safety. The present review addresses some alternative approaches to
      the study of human error, and their implications for the characterization of
      medical error. RECENT FINDINGS: The complex nature of healthcare work has been
      proposed as a primary barrier to the implementation of effective safety measures.
      Approaches to error, based on individual accountability, cannot address this
      complexity. Strategies to eradicate error fail to appreciate that error detection
      and recovery are integral to the function of complex cognitive systems. Through
      investigation of the emergence of and recovery from error, one can identify new
      approaches for error management. SUMMARY: The present review discusses
      contemporary approaches to error that are able to address the complex nature of
      critical care work. Instead of producing situation-specific 'quick fixes', they
      are more likely to reveal generalizable mechanisms of error that can support
      widely applicable solutions.

PMID- 18614913
TI  - The science of implementation: changing the practice of critical care.
AB  - PURPOSE OF REVIEW: Few would disagree that evidence from clinical research should
      be brought to the bedside in an efficient and equitable manner. Unfortunately,
      this common agreement does not result in practice change at the bedside where
      delayed and variable implementation is common. Recognition of this gap has
      resulted in a new discipline called implementation science that seeks to
      understand the reasons for slow adoption of clinical therapeutics and to discover
      effective strategies that accelerate practice change. This article reviews
      implementation theory and strategies and their effectiveness and relevance to
      critical care. RECENT FINDINGS: The absence of a proven effective framework for
      implementing clinical practice change has resulted in a patchwork of
      interventions in ambulatory and acute care medicine. There is an increasing
      appreciation that interventions should be undertaken only after careful, theory
      based examination of the source and strength of the evidence, the organizational
      and professional context in which the change will be made, and the availability
      of facilitating methods. Barriers to implementing sepsis management programs have
      been identified and, in some cases, overcome. SUMMARY: Changing clinical practice
      is sometimes as difficult as the basic science and clinical trials work that led
      to the discovery of beneficial therapies. Investigators are now beginning to
      develop and test more theory-based implementation models that are relevant to the
      clinical environment. A proportion of the resources used in developing an ICU
      guideline or protocol must be dedicated to the implementation strategy for
      successful adoption. ICUs are ideal organizations to test new approaches in
      implementation science. Intensive care professionals should insist that their
      practice environment have both a culture that is supportive of adopting new
      practices and adequate resources to implement them into patient care.

PMID- 18614914
TI  - Bibliography. Current world literature. Pharmacology, metabolism and nutrition.

PMID- 18614915
TI  - Optimization of the oligonucleotide ligation assay, a rapid and inexpensive test
      for detection of HIV-1 drug resistance mutations, for non-North American
      variants.
AB  - OBJECTIVE: We evaluated the feasibility of the oligonucleotide ligation assay
      (OLA), a specific, sensitive, and economical ligase-based point mutation assay
      designed to detect HIV-1 drug-resistance mutations at 12 codons of HIV-1 subtype
      B pol, for potential use in resource-poor settings. METHODS: Specimens from HIV-1
      infected individuals collected by 7 international laboratories, including
      subtypes A, B, C, D, F, G, J, and recombinants AE and AG, were tested by the OLA
      developed for HIV-1 subtype B. Common polymorphisms that interfered with
      reactivity of the OLA were identified and modified probes designed and evaluated.
      RESULTS: 92.5% (2,410) of 2,604 codons in specimens from 217 individuals were
      successfully genotyped by the subtype B OLA. A high rate (range 8.3%-31.2%) of
      indeterminate results (negative OLA reaction for both mutant and wild type) was
      observed for 5 codons. Modified probes at reverse transcriptase codons 151 and
      184 and protease codon 90 increased the rate of valid OLA to 96.1%. CONCLUSIONS:
      The OLA designed for HIV-1 subtype B genotyped most pol codons in non-B subtypes
      from Asia and Africa but was improved by addition of several modified probes.
      International laboratories experienced in molecular techniques were able to
      perform the OLA.

PMID- 18614916
TI  - Effect of HAART on incident cancer and noncancer AIDS events among male HIV
      seroconverters.
AB  - OBJECTIVE: To explore the impact of highly active antiretroviral therapy (HAART)
      on the prevention of AIDS-defining cancers relative to other AIDS-defining
      events. DESIGN: Prospective cohort study using 2,121 HIV+ male seroconverters
      (median age: 28 years, 51% white/non-Hispanic) in the Tri-Service AIDS Clinical
      Consortium (n = 1694) and the Multicenter AIDS Cohort Study (n = 427). METHODS:
      Poisson regression models, with calendar periods to represent antiretroviral
      therapy, were extended to analyze first incident AIDS-defining cancers and other
      first AIDS-defining events as competing risks. RESULTS: Eighty-one AIDS-defining
      cancers (64 Kaposi sarcomas; 17 non-Hodgkin lymphomas) and 343 other AIDS events
      occurred during 14,483 person-years in 1990-2006. The rate ratio of AIDS-defining
      cancers during the HAART calendar period was 0.26 (95% confidence limits: 0.15,
      0.46) and of other AIDS-defining events was 0.28 (95% confidence limits: 0.21,
      0.36) compared with the monotherapy/combination therapy calendar period,
      adjusting for age, infection duration, race, and cohort. The association of HAART
      with decreased AIDS incidence seemed to be equal (interaction ratio = 0.95 (95%
      confidence limits: 0.51, 1.74) for AIDS-defining cancers and other AIDS-defining
      events. CONCLUSIONS: In human immunodeficiency virus-infected men, HAART seems
      equally protective against first AIDS-defining cancers and other first AIDS
      defining events.

PMID- 18614917
TI  - Low prevalence of detectable HIV plasma viremia in patients treated with
      antiretroviral therapy in Burkina Faso and Mali.
AB  - BACKGROUND: Sub-Saharan Africa has seen dramatic increases in the numbers of
      people treated with antiretroviral therapy (ART). Although standard ART regimens
      are now universally applied, viral load measurement is not currently part of
      standard monitoring protocols in sub-Saharan Africa. METHODS: We describe the
      prevalence of inadequate virological response (IVR) to ART (viral load >or= 500
      copies/mL) and identify factors associated with this outcome in 606 HIV-positive
      patients treated for at least 6 months. Recruitment took place in 7 hospitals and
      community-based sites in Bamako and Ouagadougou, and information was collected
      using medical charts and interviews. RESULTS: The overall prevalence of IVR in
      treatment-naive patients was 12.3% and 24.4% for pretreated patients. There were
      no differences in rates of IVR according to ART delivery sites and time on
      treatment. Patients living farther away [odds ratio (OR) = 2.48; 95% confidence
      interval (CI) 1.40 to 4.39], those on protease inhibitor or nucleoside reverse
      transcriptase inhibitor regimens (OR = 3.23; 95% CI 1.79 to 5.82) and those
      reporting treatment interruptions (OR = 2.36; 95% CI 1.35 to 4.15), had increased
      odds of IVR. Immune suppression (OR = 3.32, 95% CI 1.94 to 5.70) and poor self
      rated health (OR = 2.00; 95% CI 1.17 to 3.41) were also associated with IVR.
      CONCLUSIONS: Sufficient expertise and dedication exist in public hospital and
      community-based programs to achieve rates of treatment success comparable to
      better-resourced settings.

PMID- 18614919
TI  - Burden of depression among impoverished HIV-positive women in Peru.
AB  - OBJECTIVES: In resource-poor settings, the mental health burden among HIV
      positive women is exacerbated by poverty. We sought to describe the extent, risk
      factors, and experience of depression among impoverished HIV-positive women
      living in Lima, Peru. METHODS: This is a case series of 78 HIV-positive women in
      Lima, Peru. We measured depression, stigma, and social support and performed a
      multivariable analysis to identify factors associated with depression. RESULTS:
      Among 78 HIV-positive patients, 68% were depressed. Depression and suicidal
      ideation were rarely diagnosed by providers. In multivariable analysis, HIV
      related stigma and food scarcity were associated with depression. CONCLUSIONS: In
      our cohort of HIV-positive women in Lima, Peru, poverty and socioeconomic
      vulnerability contributed to depression. Findings highlight the heavy burden of
      depression in this cohort of poor women and the need to incorporate mental health
      services as an integral component of HIV care.

PMID- 18614921
TI  - Chronic kidney disease prevalence and risk factors among HIV-infected patients.

PMID- 18614918
TI  - Patterns of individual and population-level adherence to antiretroviral therapy
      and risk factors for poor adherence in the first year of the DART trial in Uganda
      and Zimbabwe.
AB  - BACKGROUND: Good adherence is essential for successful antiretroviral therapy
      (ART) provision, but simple measures have rarely been validated in Africa.
      METHODS: This was an observational analysis of an open multicenter randomized
      HIV/AIDS management trial in Uganda and Zimbabwe. At 4-weekly clinic visits, ART
      drugs were provided and adherence measured through pill usage and questionnaire.
      Viral load response was assessed in a subset of patients. Drug possession ratio
      (percentage of drugs taken between visits) defined complete (100%) and good
      (>or=95%) adherence. RESULTS: In 2,957 patients, 90% had pill counts at every
      visit. Good adherence increased from 87%, 4 weeks after ART initiation, to 94% at
      48 weeks, but only 1,454 (49%) patients achieved good adherence at every visit in
      the first year. Complete adherence was associated with 0.32 greater reduction in
      log10 viral load (95% confidence interval 0.05, 0.60 P = 0.02) and was
      independently associated with higher baseline CD4 count, starting ART later in
      the trial, reporting a single regular sexual partner, clinical center, and time
      on ART. CONCLUSIONS: Population level adherence improved over time suggesting an
      association with clinical experience. Most patients had at least one visit in the
      year on which they reported not having good adherence, showing the need for
      continued adherence interventions.

PMID- 18614920
TI  - Vitamin content of breast milk from HIV-1-infected mothers before and after flash
      heat treatment.
AB  - BACKGROUND: World Health Organization advocates heat treatment of expressed
      breastmilk (EBM) as one method to reduce postnatal transmission of human
      immunodeficiency virus (HIV) in developing countries. Flash-heat is a simple heat
      treatment method shown to inactivate cell-free HIV. OBJECTIVE: To determine the
      effect of flash-heat on vitamin content of milk. METHODS: Fresh EBM was collected
      from 50 HIV+ mothers in Durban, South Africa. Mothers washed their hands and then
      manually expressed 75-150 mL EBM into sterile jars. Milk was aliquoted to
      unheated controls or flash-heat (50 mL EBM in a glass jar heated in a 450-mL
      water jacket in an aluminum pan until water boiled, then EBM removed) simulating
      field conditions with an open flame. Samples were stored at -70 degrees C and
      then analyzed for the effect of flash-heat on vitamins [A, ascorbic acid,
      riboflavin (B2), pyridoxal-5-phosphate (B6), folate, and B12]. RESULTS: Vitamin A
      was not significantly affected by flash-heat and vitamins B12 and C and folate
      increased significantly. Vitamins B2 and B6 were decreased to 59% (95% confidence
      interval 44 to 81) and 96% (95% confidence interval 92 to 99), respectively, of
      that found in unheated milk. CONCLUSIONS: The percentage remaining after flash
      heat suggests that most vitamin concentrations are retained after heating. Flash
      heat may be a practical and nutritious infant feeding method for mothers in
      developing countries.

PMID- 18614922
TI  - The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the
      replication defect associated with the K65R mutation.
AB  - BACKGROUND: The K65R mutation in human immunodeficiency virus type 1 reverse
      transcriptase can be selected by abacavir, didanosine, tenofovir, and stavudine
      in vivo resulting in reduced susceptibility to these drugs and decreased viral
      replication capacity. In clinical isolates, K65R is frequently accompanied by the
      A62V and S68G reverse transcriptase mutations. METHODS: The role of A62V and S68G
      in combination with K65R was investigated using phenotypic, viral growth
      competition, pre-steady-state kinetic, and excision analyses. RESULTS: Addition
      of A62V and S68G to K65R caused no significant change in human immunodeficiency
      virus type 1 resistance to abacavir, didanosine, tenofovir, or stavudine but
      partially restored the replication defect of virus containing K65R. The triple
      mutant K65R+A62V+S68G still showed some replication defect compared with wild
      type virus. Pre-steady-state kinetic analysis demonstrated that K65R resulted in
      a decreased rate of incorporation (kpol) for all natural dNTPs, which were
      partially restored to wild-type levels by addition of A62V and S68G. When added
      to K65R and S68G, the A62V mutation seemed to restore adenosine triphosphate
      mediated excision of tenofovir to wild-type levels. CONCLUSIONS: A62V and S68G
      serve as partial compensatory mutations for the K65R mutation in reverse
      transcriptase by improving the viral replication capacity, which is likely due to
      increased incorporation efficiency of the natural substrates.

PMID- 18614925
TI  - Efavirenz in human breast milk, mothers', and newborns' plasma.
AB  - BACKGROUND AND METHODS: Highly active antiretroviral therapy with efavirenz (EFV)
      has been prescribed to HIV-positive pregnant women in Rwanda (HIV status 1 and
      CD4 cell count > 350 cells/mm) during the last trimester of pregnancy and for 6
      months after delivery. The EFV concentrations in maternal plasma, breast milk and
      in newborns' plasma of 13 women and their children between 6 weeks and 6 months
      post partum are reported. RESULTS: Results show a mean EFV plasma concentration
      of 6.55 mg/L in maternal plasma, 3.51 mg/L in skim milk, and 0.85 mg/L in infant
      plasma. Significant linear correlations between maternal plasma and skim milk (r
      = 0.8666, P < 0.0001) and between skim milk and infant plasma (r = 0.6646, P <
      0.02) were found, but no significant correlation was observed between maternal
      and infant plasma concentrations (P > 0.05). CONCLUSIONS: After 6 months of
      breast-feeding, no child out of the 13 had been infected with HIV and all had
      good psychomotor and growth development. Our results suggest that EFV may be an
      alternative to nevirapine (NVP) during the third trimester of pregnancy and
      during the breast-feeding period. Further studies on larger groups of newborns
      will be necessary to get a better understanding of possible prophylactic
      protection of the newborns by highly active antiretroviral therapy with EFV given
      to the mothers.

PMID- 18614924
TI  - Insulin-like growth factor-1 and lean body mass in HIV-infected children.
AB  - OBJECTIVES: To describe insulin-like growth factor-1 (IGF-1) and insulin-like
      growth factor-1-binding protein-1 (IGFBP-1) and IGFBP-3 in HIV+ children before
      and after initiating or changing antiretroviral therapy and to evaluate
      association of growth and body composition to growth factors at baseline and over
      time. METHODS: Ninety-seven prepubertal HIV+ children aged 1 month to younger
      than 13 years were observed over 48 weeks after beginning or changing
      antiretroviral therapy. Serum IGF-1, IGFBP-1, and IGFBP-3 were measured and
      compared with age- and sex-specific norms. Anthropometric measures were compared
      as follows: subjects vs matched children from (a) the National Health and
      Nutrition Examination Survey to generate z scores and (b) HIV-exposed, uninfected
      children from Women and Infants Transmission Study; and subjects with normal vs
      abnormal IGF-1 and IGFBP concentrations at baseline. Anthropometric changes were
      compared for children whose IGF-1 level normalized vs remaining subjects.
      Multivariate analysis adjusting for sex, race, and baseline age evaluated
      associations between anthropometry and IGF-1 and IGFBP concentrations. RESULTS:
      In multivariate analysis, lower baseline IGF-1 and IGFBP-3 were associated with
      lower mean weight, height, mid-arm muscle circumference, and mid-thigh
      circumference z scores. Twenty-four percent of children had a low IGF-1 level at
      baseline, 50% of whom normalized IGF-1 on study. Children whose IGF-1 normalized
      had greater increases in mean mid-arm muscle circumference z score (1.00 vs 
      0.03, P = 0.029), but a trend toward lesser mean height increase (P = 0.082) than
      remaining subjects. Likewise, in comparison to controls from Women and Infants
      Transmission Study, mean mid-arm muscle circumference also increased more in
      children whose IGF-1 normalized (P = 0.024) but mean height changed less (P =
      0.003). Fifty-five percent of children had elevated IGFBP-1 at baseline, 69% of
      whom normalized. CONCLUSIONS: IGF-1 increases and IGFBP-1 decreases in HIV
      infected children upon initiation or change in antiretroviral therapy. Improved
      muscle mass, but not linear growth, is associated with normalized IGF-1
      concentration. These findings suggest that IGF-1 may merit evaluation as a
      potential therapeutic strategy to improve lean body mass in HIV-infected
      children.

PMID- 18614926
TI  - Lipid and apoprotein profile in HIV-1-infected patients after CD4-guided
      treatment interruption.
AB  - OBJECTIVES: The aims of the present study were to determine if metabolic
      abnormalities and cytokine derangements are modified in HIV-1-infected patients
      after 12 months on treatment interruption (TI). DESIGN: The design of this study
      was prospective randomized study. METHODS: Longitudinal multicenter study in HIV
      1-infected patients with a 12-month follow-up. Patients on stable highly active
      antiretroviral therapy, with CD4 count >600/microL and HIV RNA <50 copies/mL for
      at least 6 months, were randomized to interrupt therapy or continue ongoing
      highly active antiretroviral therapy. Lipids (total cholesterol, triglycerides),
      apoproteins (A1, B, and E), and adipocytokines (leptin, adiponectin, plasminogen
      activator inhibitor-1, monocyte chemotactic protein-1, Interleukin-6, Interleukin
      8, and tumor necrosis factor-alpha) were measured at baseline and at month 12.
      Multiplex suspension bead array immunoassay was performed using the Luminex 100
      analyzer to identify protein expression in plasma. RESULTS: Patients who
      underwent TI (n = 19) had a significant decrease in median cholesterol levels (P
      < 0.001), while median triglyceride levels remained unchanged. There was a
      significant decrease in Apo-A1 levels (P = 0.048) and Apo-B levels (P < 0.001)
      and an increase in tumor necrosis factor-alpha levels (P = 0.034). Given the
      greater decrease in Apo-B, the ratio Apo-A1/Apo-B increased after 12 months of TI
      (from 3.4 to 5.1, P = 0.008). We did not find significant variations in leptin or
      adiponectin levels. In patients who continued on highly active antiretroviral
      therapy (n = 18), there were no significant changes in any of the measured
      parameters. CONCLUSION: The lipid profile and apoproteins levels change toward a
      less atherogenic profile after TI, arguing against a lipid-mediated mechanism to
      explain the increased cardiovascular risk in patients who interrupt treatment.

PMID- 18614923
TI  - Adherence to antiretrovirals among US women during and after pregnancy.
AB  - BACKGROUND: Antiretrovirals (ARVs) are recommended for maternal health and to
      reduce HIV-1 mother-to-child transmission, but suboptimal adherence can
      counteract its benefits. OBJECTIVES: To describe antepartum and postpartum
      adherence to ARV regimens and factors associated with adherence. METHODS: We
      assessed adherence rates among subjects enrolled in Pediatric AIDS Clinical
      Trials Group Protocol 1,025 from August 2002 to July 2005 on tablet formulations
      with at least one self-report adherence assessment. Perfectly adherent subjects
      reported no missed doses 4 days before their study visit. Generalized estimating
      equations were used to compare antepartum with postpartum adherence rates and to
      identify factors associated with perfect adherence. RESULTS: Of 519 eligible
      subjects, 334/445 (75%) reported perfect adherence during pregnancy. This rate
      significantly decreased 6, 24, and 48 weeks postpartum [185/284 (65%), 76/118
      (64%), and 42/64 (66%), respectively (P < 0.01)]. Pregnant subjects with perfect
      adherence had lower viral loads. The odds of perfect adherence were significantly
      higher for women who initiated ARVs during pregnancy (P < 0.01), did not have
      AIDS (P = 0.02), never missed prenatal vitamins (P < 0.01), never used marijuana
      (P = 0.05), or felt happy all or most of the time (P < 0.01). CONCLUSIONS:
      Perfect adherence to ARVs was better antepartum, but overall rates were low.
      Interventions to improve adherence during pregnancy are needed.

PMID- 18614928
TI  - Using modeling to explore the degree to which a microbicide's sexually
      transmitted infection efficacy may contribute to the HIV effectiveness measured
      in phase 3 microbicide trials.
AB  - BACKGROUND: Several microbicide candidates show activity against pathogens that
      cause sexually transmitted infections (STIs). This may increase a microbicide's
      impact on HIV in phase 3 trials. Modeling is used to estimate the degree to which
      a microbicide's STI efficacy contributes to the HIV effectiveness of a phase 3
      microbicide trial. METHODS: An expression is derived and coupled with an STI
      model to estimate how much a microbicide's STI efficacy contributes to a trial's
      HIV effectiveness. The STI model estimates the decrease in STI prevalence that
      may occur in the trial's active gel arm for microbicides of different STI
      efficacy. Projections are produced for different STI cofactors and
      epidemiological settings. RESULTS: The model projects that if a microbicide is
      active against curable STIs with a combined prevalence of >or=10% among trial
      participants and the reduction in HIV incidence is <50%, then the STI activity
      could have substantially contributed to the trial's HIV effectiveness (>50% in
      some cases) if the per exposure multiplicative STI cofactor is 2.5 or greater.
      However, if the STI prevalence is <10% or the STI cofactor is <2.5 or if the
      reduction in HIV incidence is >50%, then the trial's HIV effectiveness will be
      mainly due to its direct HIV efficacy. CONCLUSIONS: In high STI settings, phase 3
      trials documenting a moderate impact on HIV incidence may partially result from a
      gel's activity against curable STI. Care should be taken generalizing these trial
      results to other settings. This is less important for trials documenting large
      reductions in HIV incidence.

PMID- 18614927
TI  - Incidence and epidemiology of anal cancer in the multicenter AIDS cohort study.
AB  - OBJECTIVE: To examine the incidence and risk factors for anal cancer in a
      multicenter cohort of human immunodeficiency virus (HIV) positive and HIV
      negative men who have sex with men followed between 1984 and 2006 (Multicenter
      AIDS Cohort Study). METHODS: Prospective analysis using Poisson regression and
      Cox proportional hazard models and a nested case-control study using conditional
      logistic regression. RESULTS: There were 28 cases of anal cancer among the 6,972
      men who were evaluated. The incidence rate was significantly higher in HIV
      positive men than in HIV-negative men (incidence rate = 69 vs 14 per 100,000
      person-years). Among HIV-positive men, anal cancer incidence was higher in the
      highly active antiretroviral therapy (HAART) era than the pre-HAART era
      (incidence rate = 137 vs 30 per 100,000 person-years). In multivariate analysis
      restricted to the HAART era, anal cancer risk increased significantly with HIV
      infection (relative hazard = 4.7, 95% confidence interval = 1.3 to 17) and
      increasing number of unprotected receptive anal sex partners at the first 3 study
      visits (P trend = 0.03). Among HIV-positive men, current HAART use did not
      decrease anal cancer risk. CONCLUSIONS: HIV-positive men had increased risk of
      anal cancer. Improved survival of HIV-positive individuals after HAART initiation
      may allow for sufficient time for human papillomavirus-associated anal dysplasias
      to develop into malignancies, thus explaining the increased incidence of anal
      cancer in the HAART era.

PMID- 18614929
TI  - CD4 independent binding of HIV gp120 to mannose receptor on human spermatozoa.
AB  - OBJECTIVE: To characterize the CD4-independent HIV-binding protein of 160 kDa on
      human spermatozoa. METHODS: The N-terminal amino acid sequence of the 160 kDa
      protein and its peptide obtained by tryptic digestion were determined. Polymerase
      chain reaction amplification of human testicular cDNA was performed using
      degenerate primers corresponding to peptide sequences of the 160 kDa protein.
      Localization of 160 kDa protein on sperm was performed using fluorescently
      labeled gp120, followed by inhibition experiments using antagonists to determine
      the specificity. RESULTS: The partial cDNA sequence of the 160 kDa protein
      demonstrated 99% identity with human macrophage mannose receptor. Sequence of
      testicular mannose receptor was obtained and exhibited 99% identity with that of
      macrophage mannose receptor. Furthermore, mannose receptor protein from sperm
      extract was found to have a molecular weight of 160 kDa, congruent with that of
      160 kDa HIV-binding protein. gp120 binding and mannose receptor expression were
      localized to the equatorial segment in 10% of ejaculated sperm, which increased
      after capacitation. Mannan at molar excess concentrations completely inhibited
      gp120 binding to sperm. CONCLUSIONS: The 160 kDa, CD4-independent HIV-binding
      sperm protein has been identified as the human mannose receptor protein. The role
      of mannose receptor in HIV transmission and association with risk of sexual
      transmission merit further investigation.

PMID- 18614930
TI  - Lymphocyte mitochondrial depolarization and apoptosis in HIV-1-infected HAART
      patients.
AB  - BACKGROUND: Efavirenz (EFV) and nevirapine (NVP), unlike nucleoside reverse
      transcriptase inhibitor drugs, do not inhibit mitochondrial (mt) polymerase gamma
      (Pol-gamma), although EFV has been shown to induce mt depolarization (Deltapsim)
      in vitro at supratherapeutic concentrations. However, the capacity of
      nonnucleoside reverse transcriptase inhibitor drugs to induce mt toxicity in vivo
      remains undetermined. OBJECTIVE: To determine the influence of EFV and NVP on
      peripheral lymphocyte mt transmembrane potential (Deltapsim) and apoptosis in HIV
      1-infected patients treated with these nonnucleoside reverse transcriptase
      inhibitors. METHODS: Thirty-two HIV-1-infected patients on highly active
      antiretroviral therapy (HAART) between 4 and 24 months (12 on EFV, 20 on NVP) and
      16 HAART-naive HIV-1-infected patients were enrolled into this study. All
      participants were black South African patients. Spontaneous peripheral lymphocyte
      apoptosis and Deltapsim were measured ex vivo by flow cytometry for all patients.
      RESULTS: : CD4 T-helper apoptosis for the EFV and NVP cohorts was 19.38% +/-
      2.62% and 23.35% +/- 1.51% (mean +/- SEM), respectively, whereas total lymphocyte
      Deltapsim was 27.25% +/- 5.05% and 17.04% +/- 2.98%, respectively. Both
      parameters for each cohort were significantly lower (P < 0.05) than that of the
      HAART-naive patients. The NVP cohort exhibited both a significant time-dependent
      increase in peripheral lymphocyte Deltapsim (P = 0.038) and correlation between T
      helper apoptosis and Deltapsim (P = 0.0005). These trends were not observed in
      the EFV cohort. CONCLUSIONS: This study provides evidence that both EFV and NVP
      induce peripheral lymphocyte Deltapsim in HIV-1-infected patients on
      nonnucleoside reverse transcriptase inhibitor-based HAART, which in the case of
      NVP is sufficient to induce the apoptosis cascade.

PMID- 18614931
TI  - Candida albicans-induced DC activation partially restricts HIV amplification in
      DCs and increases DC to T-cell spread of HIV.
AB  - Dendritic cells (DCs) are central to the innate and adaptive responses needed to
      control pathogens, yet HIV exploits DCs to promote infection. The influence of
      other pathogens on DC-HIV interplay has not been extensively studied. We used
      Candida albicans (Candida) as a model pathogen which elicits innate DC responses
      that are likely important in controlling Candida by healthy immune systems. HIV
      did not impede Candida-specific DC activation. Candida-induced CD80 and CD83
      upregulation was greater in DCs that had captured HIV, coinciding with increased
      amplification in presence of T cells and reduced but persistent low-level DC
      infection. In contrast, HIV-infected DCs matured normally in response to Candida,
      but this did not shut down HIV replication in DCs, and again Candida augmented
      HIV amplification in DC-T-cell mixtures. HIV-infected DCs secreted more IL-10 and
      IL-1beta earlier than uninfected DCs and initially induced a higher frequency of
      CD4CD25FoxP3 T-regulatory cells in response to Candida. Elevated early IL-10
      production in cocultures was evident only when azidothymidine (AZT) was included
      to limit T-regulatory cell infection and destruction. Therefore, HIV manipulates
      the DC's innate and adaptive responses to Candida to further augment HIV spread,
      ultimately destroying the cells needed to limit candidiasis.

PMID- 18614932
TI  - Interaction of hepatitis B and C viruses in patients infected with HIV.

PMID- 18614933
TI  - Mortality rate of early versus deferred initiation of antiretroviral therapy in
      HIV-1-infected patients with cryptococcal meningitis.

PMID- 18614934
TI  - Intermittent versus continuous exercise: effects of perceptually lower exercise
      in obese women.
AB  - INTRODUCTION: Exercise has beneficial effects on obesity and diabetes treatments.
      However, obese subjects do not closely adhere to training programs probably
      because of the monotony of the continuous exercise that is frequently proposed.
      To increase adherence to training programs, intermittent exercise, which is less
      monotonous, may be more appropriate. PURPOSE: The purposes of this study were to
      determine the perceptually less hard exercise (continuous vs intermittent
      exercise) and to analyze the impact of a training program on the basis of this
      exercise in obese women with and without type 2 diabetes. METHODS: Twenty type 2
      diabetic obese women and 20 obese women without diabetes were recruited. In each
      group, 10 patients integrated a training program (i.e., training groups), whereas
      the remaining patients were untrained (i.e., control groups). The training groups
      performed a continuous exercise and an intermittent exercise to determine the
      perceptually less hard exercise thanks to lower ratings of perceived exertion
      (RPE). Then, a training program that included 32 min (3 d x wk(-1) x 10 wk(-1))
      of the perceptually less hard exercise was proposed to training groups. RESULTS:
      RPE were significantly lower during the intermittent exercise compared to the
      continuous exercise in the obese women with or without diabetes (RPE = 12.3 +/-
      2.3 vs 13.7 +/- 2.3 and RPE = 11.9 +/- 1.1 vs 13.2 +/- 1.6, respectively). After
      the training program, significant beneficial effects on the glycosylated
      hemoglobin (6.8 +/- 1.4% vs 6.5 +/- 1.2%), body mass (97.1 +/- 16.9 vs 95.2 +/-
      16.2 kg), body mass index (37.6 +/- 6.1 vs 36.8 +/- 6.0 kg x m(-2)), and on the
      HR and the walked distance limit were noticed in the training groups. CONCLUSION:
      The obese women with or without diabetes perceived the intermittent exercise as
      being less hard than the continuous exercise, and a training program based on
      intermittent exercises produced beneficial effects on obesity and type 2
      diabetes.

PMID- 18614935
TI  - Occupational relevance and body mass bias in military physical fitness tests.
AB  - Recent evidence makes a compelling case that US Army, Navy, and Air Force health
      related physical fitness tests penalize larger, not just fatter, service members.
      As a result, they tend to receive lower scores than their lighter counterparts,
      the magnitude of which can be explained by biologic scaling laws. Larger
      personnel, on the other hand, tend to be better performers of work-related
      fitness tasks such as load carriage, heavy lifting, and materiel handling. This
      has been explained by empirical evidence that lean body mass and lean body mass
      to dead mass ratio (dead mass = fat mass and external load to be carried/lifted)
      are more potent determinants of performance of these military tasks than the
      fitness test events such as push-ups, sit-ups, or 2-mile-distance run time.
      Because promotions are based, in part, on fitness test performance, lighter
      personnel have an advancement advantage, although they tend to be poorer
      performers on many tests of work-related fitness. Several strategies have been
      proposed to rectify this incongruence including balanced tests, scaled scores,
      and correction factors--yet most need large-scale validation. Because nearly all
      subjects in such research have been men, future investigations should focus on
      women and elucidate the feasibility of universal physical fitness tests for all
      that include measures of health- and work-related fitness while imposing no
      systematic body mass bias.

PMID- 18614936
TI  - Do practical durations of stretching alter muscle strength? A dose-response
      study.
AB  - PURPOSE: To examine the time course (immediate, 10, 20, and 30 min) for the acute
      effects of 2, 4, and 8 min of passive stretching (PS) on isometric peak torque
      (PT), percent voluntary activation (%VA), EMG amplitude, peak twitch torque
      (PTT), rate of twitch torque development (RTD), and range of motion (ROM) of the
      plantarflexors. METHODS: Thirteen volunteers (mean +/- SD age, 22 +/- 3 yr)
      participated in four randomly ordered experimental trials: control (CON) with no
      stretching, 2 min (PS2), 4 min (PS4), and 8 min (PS8) of PS. Testing was
      conducted before (pre), immediately after (post), and at 10, 20, and 30 min
      poststretching. The PS trials involved varied repetitions of 30-s passive
      stretches, whereas the CON trial included 15 min of resting. PT, %VA, EMG
      amplitude, PTT, and RTD were assessed during the twitch interpolation technique,
      whereas ROM was quantified as the maximum tolerable angle of passive
      dorsiflexion. RESULTS: PT decreased (P < or = 0.05) immediately after all
      conditions [CON (4%), PS2 (2%), PS4 (4%), and PS8 (6%)] but returned to baseline
      at 10, 20, and 30 min poststretching. %VA and EMG amplitude were unaltered (P >
      0.05) after all conditions. PTT and RTD decreased (P < or = 0.05) immediately
      after the PS4 (7%) and the PS8 (6%) conditions only; however, these changes were
      not sufficient to alter voluntary force production. There were also increases (P
      < or = 0.05) in ROM after the PS2 (8%), the PS4 (14%), and the PS8 (13%)
      conditions that returned to baseline after 10 min. CONCLUSION: Practical
      durations of stretching (2, 4, or 8 min) of the plantarflexors did not decrease
      isometric PT compared with the CON but caused temporary improvements in the ROM,
      thereby questioning the overall detrimental influence of PS on performance.

PMID- 18614937
TI  - Biomechanics of ankle instability. Part 2: Postural sway-reaction time
      relationship.
AB  - PURPOSE: To test the hypothesis that ankles with functional instability will
      demonstrate greater single-limb postural sway (PS) than their contralateral
      stable joint and stable healthy controls and to examine the relationship between
      single-limb postural sway and muscular reaction time to a simulated ankle sprain
      mechanism. METHODS: Nineteen male volunteers with a history of unilateral ankle
      sprain and functional ankle instability (FAI) and 19 healthy male controls
      performed 12 single-limb PS tests, 3 on each leg with and without vision.
      Participants provided informed consent. Postural sway data are reported on the
      FAI group's unstable (UA) and stable ankles (SA), and the control group's
      dominant (DA) and nondominant ankles (NDA). RESULTS: With vision, the UA and SA
      revealed similar postural control; however, the UA showed greater (P < 0.05)
      anteroposterior PS than the DA (0.46 cm) and the NDA (0.51 cm). Without vision,
      the UA showed greater (P < 0.05) medial (2.41 cm) and lateral (2.59 cm) PS than
      the SA and also showed greater (P < 0.05) medial (2.05 and 2.10 cm, respectively)
      and lateral (2.28 and 2.26 cm, respectively) than the DA and NDA. The
      relationship between PS and muscle reaction times, derived from the previous
      article was calculated. Significant correlations (P < 0.05) were found between
      the unstable ankle peroneus longus (PL) and peroneus brevis (PB) reaction time
      and lateral (r = 0.63 and r = 0.81, respectively), medial (r = 0.74 and r = 0.76,
      respectively), and anterior PS (r = 0.56 and r = 0.55, respectively; P < 0.01).
      CONCLUSIONS: Results reveal postural sway deficits in ankles with FAI. They also
      demonstrate a significant relationship between PL and PB reaction times and
      postural sway in UA. Individuals who sustain an acute ankle sprain and those with
      FAI require rehabilitation that improves proprioception, strengthens the evertors
      and dorsiflexors, and restores peroneal reaction time.

PMID- 18614938
TI  - Energetic costs of incidental visual coupling during treadmill running.
AB  - PURPOSE: To determine the role of visual-spatial information in stabilizing
      movement during treadmill locomotion. METHODS: Physiological, biomechanical, and
      psychological indices of coordination stability were recorded while participants
      were visually coupled with a whole-body image of themselves during treadmill
      locomotion. Ten participants ran on a treadmill under three visual conditions:
      two dynamic images (symmetrical, mirror image; asymmetrical, reversed mirror
      image) and one static. Performance was examined at two speeds. RESULTS:
      Participants ran more economically (mL x kg x min(-1)) when they were visually
      coupled with a symmetrical rather than with an asymmetrical or static image. An
      asymmetrical coupling resulted in increased variability in footfall position at
      the faster speed, in comparison to the symmetrical and static conditions.
      However, at slower speeds, footfall variability and frequency were higher under
      both dynamic visual conditions in comparison to the static control. Changes in
      metabolic economy (mL x kg x min(-1)) were only partially mediated by movement
      kinematics. CONCLUSION: Visual information influences treadmill locomotion and
      associated measures of stability even when there is no intention to coordinate
      with external stimuli.

PMID- 18614939
TI  - Energy expenditure of the physical activity across the curriculum intervention.
AB  - Physical activity is frequently a component of interventions designed to diminish
      weight gain in children. It is essential to determine whether the energy
      expenditure (EE) elicited by these interventions is sufficient to reduce the rate
      of weight gain. PURPOSE: To quantify the EE of the Physical Activity across the
      Curriculum (PAAC) intervention. This intervention involved two 10-min physically
      active academic lessons per day, taught by classroom teachers. METHODS: We
      assessed EE of PAAC in 19 males and 19 females using both an indirect calorimeter
      (IC) (COSMED K4b(2)) and an accelerometer (ActiGraph) (AC). Independent t-tests
      were used to evaluate gender differences. Dependent t-tests were used to examine
      the difference between EE assessed by IC and AC. The agreement between EE
      measured by IC and estimated by AC was evaluated using a Bland-Altman plot. A
      Pearson correlation between EE measured by IC and estimated by AC was calculated.
      RESULTS: There were no significant gender differences for age, BMI, or EE;
      therefore, analyses by gender were not performed. The mean EE measured by IC was
      3.1 +/- 1.0 kcal x min(-1) (3.4 METs). Mean EE estimated by AC (1.8 +/- 0.9 kcal
      x min(-1)) was significantly lower (P < 0.05) than EE measured by IC (mean
      underestimation = 1.3 kcal x min(-1)). The Bland-Altman plot suggested increased
      underestimation with increased levels of EE. The 95% limits of agreement were
      large (-2.8 to +0.3 kcal x min(-1)). The correlation between EE measured by IC
      and estimated by AC was r = 0.68 (P < 0.001). CONCLUSION: PAAC elicited a level
      of EE that may prevent excessive weight gain in children. AC significantly
      underestimated the EE of PAAC lessons and may not provide useful EE estimates in
      this context.

PMID- 18614940
TI  - Effects of high altitude on substrate use and metabolic economy: cause and
      effect?
AB  - In a variety of experimental models, hypoxia causes a shift in substrate use to
      favor increased dependence on glucose. One explanation for this phenomenon is a
      selective advantage derived from the increased metabolic economy (more ATP
      derived per unit oxygen consumed) that results when glucose is oxidized rather
      than lipid. In support of this hypothesis, after acclimatization to hypoxia,
      lower oxygen consumption at a given submaximal workload has often been reported.
      However, evidence from several experimental models is inconsistent with the idea
      that the increase in glucose use is causally related to greater metabolic
      economy.

PMID- 18614941
TI  - Acute exercise does not cause sustained elevations in AMPK signaling or
      expression.
AB  - PURPOSE: No study has examined the response of skeletal muscle AMP-activated
      protein kinase (AMPK) signaling beyond the first 3 h after an acute exercise bout
      in humans. The purpose of this study was to assess AMPK signaling in human
      skeletal muscle immediately after a single bout of moderate-intensity endurance
      exercise and 3 and 24 h after the exercise bout. METHODS: We examined AMPK
      signaling, and protein expression of AMPK alpha, ACC-beta, and nNOS mu in
      untrained individuals (four females and four males) during the 24-h period after
      a 60-min bout of moderate-intensity (63 +/- 1% VO2peak) cycling endurance
      exercise. RESULTS: AMPK alpha2 activity, AMPK alpha2 Thr172 phosphorylation, and
      ACC-beta Ser222 phosphorylation were increased immediately after exercise. These
      increases had all returned to basal levels at 3 and 24 h after exercise.
      Furthermore, an acute bout of exercise did not alter AMPK alpha1, AMPK alpha2,
      ACC-beta, or nNOS mu protein expression during the 24-h period after exercise.
      CONCLUSION: Although an acute bout of exercise elicits increases in AMPK
      signaling, this alone is not sufficient to induce sustained increases in either
      AMPK signaling or protein expression during the postexercise period.

PMID- 18614942
TI  - Favorable and prolonged changes in blood lipid profile after muscle-damaging
      exercise.
AB  - PURPOSE: To examine the effect of repeated muscle-damaging exercise on the time
      course changes in blood lipid and lipoprotein profile and compare them with
      changes in indices of muscle function and damage. METHODS: Twelve women underwent
      an isokinetic exercise session consisting of 75 eccentric knee flexions, which
      was repeated after 3 wk. Triacylglycerols (TG), total cholesterol (TC), and high
      density lipoprotein cholesterol (HDLC) in plasma were measured before,
      immediately, 1, 2, 3, 4, and 7 d after muscle-damaging exercise. Low-density
      lipoprotein cholesterol (LDLC) and TC/HDLC were also calculated. RESULTS: The
      largest changes in TG and lipoproteins appeared 3 d after exercise, returning
      toward baseline thereafter. The magnitudes of these changes at 3 d compared with
      rest were -18% and -8% for TG, -14% and -10% for TC, 8% and 7% for HDLC, -25% and
      -18% for LDLC, and -20% and -15% for TC/HDLC after sessions 1 and 2,
      respectively. In addition, the incremental or decremental area under the curve
      for the TG and lipoproteins measured after the first session was higher than that
      after the second session--except for HDLC concentration. CONCLUSION: These
      findings reveal that lipid and lipoprotein profile was favorably affected by both
      sessions of muscle-damaging exercise but relatively less so after a repeated
      session of muscle-damaging exercise.

PMID- 18614943
TI  - Serum S-100beta response to exercise-heat strain before and after acclimation.
AB  - Exercise alone or in combination with environmental heat stress can elevate blood
      S-100beta protein concentrations. However, the explanatory power of exercise with
      marked environmental heat stress on the appearance of S-100beta is questionable.
      It is possible that the process of heat acclimation might afford additional
      insight. PURPOSE: Determine the S-100beta response to moderate-intensity exercise
      with heat strain before and after heat acclimation. METHODS: Nine healthy male
      volunteers completed 10 consecutive days of heat acclimation consisting of up to
      100 min of treadmill walking (1.56 m x s(-1), 4% grade) in the heat (45 degrees
      C, 20% relative humidity). Changes in HR, rectal temperature (T(re)), and sweat
      rate (SR) were examined to determine successful acclimation. Area under the curve
      (AUC) for T(re) greater than 38.5 degrees C was calculated to assess cumulative
      hyperthermia. Blood samples were taken before and after exercise on days 1 and 10
      and were analyzed for serum osmolality and S-100beta concentration. RESULTS: All
      subjects displayed physiological adaptations to heat acclimation including a
      significant (P < 0.05) reduction in final HR (161 to 145 bpm) and T(re) (39.0 to
      38.4 degrees C), as well as a modest (approximately 10%) increase in SR (1.10 to
      1.20 L x h(-1); P = 0.09). No differences were observed in pre- to postexercise
      serum S-100beta concentrations on day 1 or 10, and no differences were observed
      in S-100beta values between days 1 and 10. No significant correlations were found
      between S-100beta values and any variable of interest. CONCLUSIONS: S-100beta
      concentrations do not necessarily increase in response to exercise-heat strain,
      and no effect of heat acclimation on S-100beta could be observed despite other
      quantifiable physiological adaptations.

PMID- 18614944
TI  - Fractional exhaled NO and serum pneumoproteins after swimming in a chlorinated
      pool.
AB  - PURPOSE: The purpose of this study was to examine whether a swimming session
      performed in a pool sanitized with chlorine-based agents induces lung
      inflammation, modifies lung epithelium permeability, and alters lung function.
      METHODS: Eleven volunteers performed two standardized swimming sessions: one in a
      nonchlorinated indoor swimming pool and the other one in a chlorinated indoor
      pool. Lung inflammation was assessed by fractional exhaled nitric oxide (FE(NO)).
      Changes in lung epithelium permeability were estimated by measuring the
      surfactant-associated proteins Type A and Type B (SP-A and SP-B), the Clara cell
      protein (CC16), and the Krebs von den Lungen-6 protein (KL-6). Lung function
      tests were also performed. All measurements were carried out in basal conditions,
      after training completion and 3 h postexercise. Nitrogen trichloride (NCl3), the
      most concentrated gas derived from pool water chlorination, was measured in each
      pool during the swimming sessions. RESULTS: NCl3 ranged from 160 to 280 microg x
      m(-3) in the air of the chlorinated pool and was undetectable in the
      nonchlorinated one. Lung function was affected neither by the exercise session
      nor by the type of sanitation. Serum pneumoproteins were unchanged excepted SP-A
      which decreased by 8% after exercise in the chlorinated pool (P < 0.05). FE(NO)
      increased by 34% (P < 0.05) after exercise in the nonchlorinated pool, whereas it
      was unaffected in the chlorinated one. CONCLUSIONS: At concentrations lower than
      300 microg x m(-3), NCl3 in an indoor chlorinated pool, does not produce short
      term changes in lung function or in epithelial permeability. The unchanged FE(NO)
      found in the chlorinated pool after exercise suggests that chlorination might
      inhibit NO-induced vasodilation observed during exercise.

PMID- 18614945
TI  - Beta-glucan, immune function, and upper respiratory tract infections in athletes.
AB  - PURPOSE: This study investigated the effects of oat beta-glucan (BG)
      supplementation on chronic resting immunity, exercise-induced changes in immune
      function, and self-reported upper respiratory tract infection (URTI) incidence in
      human endurance athletes. METHODS: Trained male cyclists were randomized to BG (N
      = 19) or placebo (P; N = 17) groups and under double-blind procedures received BG
      (5.6 g x d(-1)) or P beverage supplements for 2 wk before, during, and 1 d after
      a 3-d period in which subjects cycled for 3 h x d(-1) at approximately 57%
      maximal watts. URTI symptoms were monitored during BG supplementation and for 2
      wk afterward. Blood samples were collected before and after 2 wk of
      supplementation (both samples, 8:00 a.m.), immediately after the 3-h exercise
      bout on day 3 (6:00 p.m.), and 14 h after exercise (8:00 a.m.) and were assayed
      for natural killer cell activity (NKCA), polymorphonuclear respiratory burst
      activity (PMN-RBA), phytohemagglutinin-stimulated lymphocyte proliferation (PHA
      LP), plasma interleukin 6 (IL-6), IL-10, IL-1 receptor agonist (IL-1ra), and IL
      8, and blood leukocyte IL-10, IL-8, and IL-1ra mRNA expression. RESULTS: Chronic
      resting levels and exercise-induced changes in NKCA, PMN-RBA, PHA-LP, plasma
      cytokines, and blood leukocyte cytokine mRNA did not differ significantly between
      BG and P groups. URTI incidence during the 2-wk postexercise period did not
      differ significantly between groups. CONCLUSIONS: An 18-d period of BG versus P
      ingestion did not alter chronic resting or exercise-induced changes in immune
      function or URTI incidence in cyclists during the 2-wk period after an
      intensified exercise.

PMID- 18614946
TI  - Exercise-induced oxidative DNA damage and lymphocytopenia in sedentary young
      males.
AB  - Post high-intensity exercise lymphocytopenia is well documented, but its
      underlying mechanisms have not been fully elucidated. A possible mechanism is a
      reactive oxygen species-induced DNA damage after high-intensity exercise.
      Furthermore, lymphocyte apoptosis related to DNA damage might contribute to
      exercise-induced lymphocytopenia. PURPOSE: This study examined lymphocytopenia,
      lymphocyte oxidative DNA damage, and apoptosis in young healthy sedentary males
      after acute high-intensity exercise. METHOD: Fifteen subjects exercised on
      bicycle ergometers for 1 h at 75% of their VO2max. Venous blood samples were
      taken before exercise (PRE) and hourly after exercise until 4 h (P0-P4).
      Lymphocyte counts, oxidative DNA damage evaluated using the Comet assay with
      human 8-oxoguanine DNA glycosylase, and serum lipid peroxide (LPO) concentration
      were measured. Furthermore, lymphocyte superoxide, Fas receptor (CD95), and
      Annexin-V-positive lymphocyte apoptosis cells were measured in 10 subjects who
      exercised and gave blood samples as described above. RESULTS: Lymphocyte counts
      became significantly lower than the PRE value (P < 0.05): 20.4% at P1, 24.3% at
      P2, and 16.3% at P3. Moreover, LPO significantly increased by P2 (P < 0.05): 1.6
      fold. The % DNA in tail, indicating oxidative DNA damage, was significantly
      higher at P3 (54.3 +/- 12.8%) than at PRE (42.6 +/- 11.1%, P < 0.05). The
      lymphocyte superoxide level was significantly higher (51.3%) than the PRE value
      (P < 0.05). Neither CD95 nor Annexin-V-positive cells were significantly
      different than the PRE value. CONCLUSION: Results of this study suggest that
      lymphocyte oxidative DNA damage can relate to lymphocytopenia, although DNA
      damage was not associated with apoptosis in healthy young sedentary males.

PMID- 18614947
TI  - Neutrophil death induced by a triathlon competition in elite athletes.
AB  - INTRODUCTION/PURPOSE: The effect of a triathlon competition on death of
      neutrophils from elite athletes was investigated. METHODS: Blood was collected
      from 11 sedentary volunteers and 12 triathletes under rest and after a Half
      Ironman triathlon competition (2-km swimming, 80-km cycling, and 20-km running).
      RESULTS: The triathlon competition increased DNA fragmentation,
      phosphatidylserine externalization, and reactive oxygen species production in
      neutrophils when compared to the results at rest. The proportion of neutrophils
      with mitochondrial transmembrane depolarization was increased in the triathletes
      at rest and after competition as compared with sedentary volunteers. Plasma
      levels of thiobarbituric acid reactive substances were increased in triathletes
      after competition. Expression of bcl-xL (antiapoptotic) was decreased and that of
      bax (proapoptotic) was increased, whereas intracellular neutral lipid content was
      lowered in neutrophils after the triathlon. A positive correlation was found
      between the proportion of neutrophils with DNA fragmentation and the plasma free
      fatty acid levels (r = 0.688, P< 0.05), which was elevated by threefold after
      competition. Plasma levels of oleic, linoleic, and stearic acids were increased
      in triathletes after the competition when compared with sedentary volunteers. The
      plasma concentration of these three fatty acids, measured after the triathlon
      competition, was toxic for 3-h cultured neutrophils obtained from sedentary
      volunteers. The maximal tolerable (nontoxic) concentration of the fatty acids by
      3-h cultured neutrophils was 100 micromol x L(-1) for oleic and linoleic acids
      and 200 micromol x L(-1) for stearic acid. CONCLUSION: The triathlon competition
      induced neutrophil death possibly by apoptosis as indicated by DNA fragmentation
      and phosphatidylserine externalization. The increase in plasma levels of oleic,
      linoleic, and stearic acids induced by the competition may be involved in the
      neutrophil death observed possibly by increasing the production of reactive
      oxygen species and by decreasing the accumulation of intracellular neutral lipid.

PMID- 18614948
TI  - Assigning energy costs to activities in children: a review and synthesis.
AB  - PURPOSE: Compendia of energy costs are often used to assign energy expenditures
      (EE) to self-reported and observed activity. As there is a lack of data on the
      energy cost of children's everyday activities, adult values are often used as
      surrogates. However, the best way to adjust adult values for use with children
      remains unclear. Various strategies have been used to estimate rates of EE in
      children. METHODS: To evaluate these existing methods for assigning EE to
      children, a literature search reviewed all English-language studies that measured
      energy costs in healthy 6.0-17.9 yr olds using criterion EE measures. Data were
      combined using the Monte Carlo simulation procedure, with walking and running
      forming separate data sets. RESULTS: The resultant data set (excluding walking
      and running) contained 5592 data points encompassing 51 activities. Analyses
      revealed using adults METs, combined with child resting metabolic rates, as the
      best existing technique to assign EE to children when measured values are not
      available. Prediction equations for the energy cost of walking and running were
      calculated using multiple regression. CONCLUSION: This study has provided a
      literature base and analytical support for a compendium of energy costs for use
      with children with energy costs expressed as METs.

PMID- 18614949
TI  - Effects of weather on pedometer-determined physical activity in children.
AB  - The effects of weather conditions on children's physical activity have not been
      well described. PURPOSE: To evaluate the effects of meteorological variables on
      the number of pedometer steps accumulated by children. METHODS: Between August
      and December 2004 (winter to summer), 1115 Auckland children (536 boys, 579
      girls; aged 5-12 yr) from 27 socioeconomically and ethnically diverse schools
      wore sealed multiday memory pedometers for five consecutive days (three weekdays
      and two weekend days). Values of daily (7 a.m. to 7 p.m.) mean ambient
      temperature, mean wind speed, precipitation, and duration of bright sunshine were
      obtained from local meteorological stations. The independent effects of each of
      these variables on step counts were estimated using composite mixed linear
      models. Effects were standardized for interpretation of magnitudes. RESULTS:
      Weekday and weekend-day step counts for boys were 16,100 +/- 5000 and 12,900+/-
      5900 (mean +/- SD), whereas those for girls were 14,200 +/- 4200 and 11,300 +/-
      4800. A 10 degrees C rise in mean ambient temperature was associated with a small
      increase in weekday steps [1700; 90% confidence intervals (CI) +/-1300] and a
      moderate increase in weekend-day steps (3400; 90% CI +/-1500) for boys, whereas
      for girls the effects were small (2300; 90% CI +/-1000) and unclear (-300; 90% CI
      +/-1200), respectively. There were substantial decreases in weekday and weekend
      day steps during moderate rainfall (1.1-4.9 mm) for both sexes. Most effects of
      day length, wind speed, and hours of bright sunshine on step counts were trivial
      or unclear. CONCLUSIONS: Ambient temperature and rainfall have substantial
      effects on children's daily step counts and should therefore be considered when
      comparing physical activity across different locations or periods. Strategies to
      increase activity on cold or rainy days may also be appropriate.

PMID- 18614950
TI  - The longitudinal effects of physical activity history on metabolic syndrome.
AB  - PURPOSE: To examine the relationship of physical activity and its changes over a
      9-yr follow-up to the prevalence of metabolic syndrome (MetS) in 2060 young
      adults (24-39 yr) enrolled in the Cardiovascular Risk in Young Finns Study.
      METHODS: Leisure-time physical activity (LTPA) was assessed using a self-report
      questionnaire completed in connection with a medical examination at two
      consecutive measurements in 1992 and 2001. By summing the LTPA items, a physical
      activity index (PAI) was formed for both measurement points according to which
      the participants were divided into tracking groups: persistently active,
      increasingly active, decreasingly active, and persistently inactive. MetS in 2001
      was defined by the guidelines of the European Group for the Study of Insulin
      Resistance (EGIR), the National Cholesterol Education Program Adult Treatment
      Panel III (NCEP-ATP III), and the International Diabetes Federation (IDF). A
      continuous metabolic risk score was also calculated by summing the z-scores for
      the metabolic risk factors. RESULTS: There was a significant linear relationship
      between MetS and LTPA at baseline in men and at follow-up in both sexes according
      to all three definitions. Persistent physical activity during 9 yr was associated
      with a lower prevalence of MetS than persistent physical inactivity on all
      definitions (all P < 0.05). Similar results were found for increasingly active
      women (all P < 0.05). All of these associations remained significant after
      adjustment for potential confounders. In both men and women, the 9-yr change in
      LTPA was related to the metabolic risk score after adjustments for baseline LTPA,
      age, smoking, and education. CONCLUSIONS: A physically active lifestyle across
      the lifespan may prevent or delay the onset of metabolic syndrome in young male
      and female adults.

PMID- 18614951
TI  - Clinical significance of cardiac damage and changes in function after exercise.
AB  - Acute bouts of ultraendurance exercise may result in the appearance of biomarkers
      of cardiac cell damage and a transient reduction in left ventricular function.
      The clinical significance of these changes is not fully understood. There seems
      to be two competing issues to be resolved. First, could prolonged endurance
      exercise produce a degree of cardiac stress and/or damage that results, during
      the short or long term, in deleterious consequences for cardiac health. Second,
      there is a clear need to educate those responsible for the medical care of
      endurance athletes about the possibility of a transient reduction in cardiac
      function and the appearance of cTnT/cTnI after an exercise. Minor elevations in
      cardiac troponins are commonplace after an endurance exercise in elite and
      recreational athletes and may occur alongside exercise-associated collapse.
      Misdiagnosis of myocardial injury and subsequent mismanagement can be
      unnecessarily expensive and psychologically damaging to the athlete. Diagnosis of
      myocardial injury after prolonged exercise should be made on the basis of all
      available information and not blood tests alone. The clinical significance of
      chronic exposure to endurance exercise is unknown. The development of myocardial
      fibrosis has been suggested as a long-term outcome to chronic exposure to
      repetitive bouts of endurance exercise and has been linked to an exercise-induced
      inflammatory process observed in an animal model. This hypothesis is supported by
      a limited number of studies reporting postmortem studies in athletes and an
      increased prevalence of complex arrhythmia in veteran athletes. Care is warranted
      in promoting this hypothesis without further detailed work, given the unequivocal
      link between exercise and mortality and morbidity. It would seem erroneous,
      however, to assume that a linear relationship exists between exercise volume and
      cardiac health.

PMID- 18614952
TI  - Exercise-associated increases in cardiac biomarkers.
AB  - At present, the risk of myocardial damage by endurance exercise is under debate
      because of reports on exercise-associated increases in cardiac biomarkers
      troponin and B-type natriuretic peptide (BNP); these markers are typically
      elevated in patients with acute myocardial infarction and chronic heart failure,
      respectively. Exercise-associated elevations of cardiac biomarkers can be present
      in elite and in recreational athletes, especially after prolonged and strenuous
      endurance exercise bouts (e.g., marathon and ultratriathlon). However, in
      contrast to cardiac patients, it is still unclear if the exercise-associated
      appearance or increase in cardiac biomarkers in obviously healthy athletes
      represents clinically significant cardiac insult or is indeed part of the
      physiological response to endurance exercise. In addition, elevations in cardiac
      biomarkers in athletes after exercise may generate difficulties for clinicians in
      terms of differential diagnosis and may result in inappropriate consequences.
      Therefore, the aim of this article is to provide an overview of exercise
      associated alterations of the cardiac biomarkers troponin T and I, ischemia
      modified albumin, BNP, and its cleaved inactive fragment N-terminal pro BNP for
      the athlete, coach, scientist, and clinician.

PMID- 18614953
TI  - Mechanisms underpinning exercise-induced changes in left ventricular function.
AB  - Despite a growing body of evidence suggesting that prolonged strenuous exercise
      (PSE) is associated with a transient reduction in right (RV) and left ventricular
      (LV) performance, the exact mechanism(s) responsible for this phenomenon is not
      fully understood. As such, the primary objective of this article was to
      critically review the available literature (both animal and human) to provide
      insight into the potential mechanism(s) responsible for the development of
      "exercise-induced cardiac fatigue." We pay particular attention to the major
      mechanisms that have been linked to transient changes in systolic function after
      PSE including altered loading conditions, myocardial ischemia/damage, altered
      beta-receptor responsiveness, and altered cardiac autonomic modulation. We also
      examine the potential mechanisms that may contribute to transient changes in
      diastolic function often observed after PSE including changes in LV pressure
      gradients and alterations in intrinsic myocardial relaxation. Although further
      mechanistic investigations are clearly warranted, several key mechanisms have
      received support for at least a partial contribution to the transient changes in
      myocardial performance often observed after PSE.

PMID- 18614954
TI  - Postexercise changes in left ventricular function: the evidence so far.
AB  - Whether prolonged exercise results in a transient depression in left ventricular
      (LV) function has been the focus of numerous studies since the 1960s. This review
      attempts to summarize the findings of this growing body of research.
      Understanding in this area has followed the advances in imaging techniques and
      specifically in echocardiographic technology. As such, the review focuses on
      evidence from the traditional echocardiographic technology (two-dimensional and
      Doppler measures), the more advanced technique of tissue Doppler imaging (TDI),
      and finally the assessment of myocardial strain and strain rate. Although many of
      the studies have adopted a similar cross-sectional pre- to postexercise design,
      there are often significant differences in terms of subject characteristics,
      exercise duration, and exercise modality. Accordingly, we draw together the
      common findings from this growing body of research in an attempt to reach a
      consensus regarding the influence of prolonged exercise on LV function.

PMID- 18614955
TI  - Exercise and the heart: can you have too much of a good thing?
AB  - Reports that participation in prolonged exercise can lead to a transient
      depression in ventricular function and/or a minor increase in biomarkers of
      cardiomyocyte insult have stimulated significant media and scientific attention
      in the last few years. Despite being of relevance to the scientist, the
      clinician, and a broad spectrum of athletes, these phenomena are poorly defined
      and controversial. Specifically, the definition and the description of these
      topics are quite limited, and conflicting data are available. Further, the
      mechanisms underpinning these events are not clear. Finally, a clear message
      related to the short- and the long-term impact on cardiovascular health and/or
      sports performance is lacking. The symposium "Exercise and the heart: Can you
      have too much of a good thing?" was presented at the ACSM Annual Meeting in New
      Orleans on June 1, 2007 to specifically address these issues. This initial
      introduction sets out the background to the main articles that will document our
      current understanding of these problems as well as suggest important avenues for
      further research.

PMID- 18614956
TI  - Effect of resistance training on blood oxidative stress in Parkinson disease.
AB  - Oxidative stress seems to be involved in the pathogenesis of Parkinson disease
      (PD). Exercise training can increase endogenous antioxidant protection and
      decrease the production of reactive oxygen and nitrogen species. PURPOSE: To
      investigate the effect of exercise training on oxidative status in persons with
      PD. METHODS: Sixteen subjects with PD were match-randomly assigned to resistance
      exercise (n = 8) or a no-exercise control group (n = 8) on the basis of disease
      stage (Hoehn and Yahr stages I and II) and sex. Supervised exercise was performed
      twice weekly for 8 wk, consisting of three sets each of the leg press, leg curl,
      and calf press. Resting blood samples were taken from subjects before and after
      the intervention and assayed for markers of oxidative stress [malondialdehyde
      (MDA) and hydrogen peroxide (H2O2)] and antioxidant capacity (superoxide
      dismutase, catalase, glutathione peroxidase, and trolox-equivalent antioxidant
      capacity). RESULTS: The exercise program was well-tolerated and associated with
      modest trends toward decreased oxidative stress and increased antioxidant
      capacity. The two biomarkers of oxidative stress were decreased after exercise
      training [MDA (15%) and H2O2 (16%)]. With these changes, a postintervention
      difference was apparent between the resistance exercise training and control
      groups for H2O2 (P = 0.007), with a trend for difference noted for MDA (P =
      0.06). The mean increases in superoxide dismutase (9%) and glutathione peroxidase
      (15%) noted in the exercise training group were not statistically significant (P
      > 0.05). CONCLUSIONS: Short-term resistance training may be associated with
      reduced oxidative stress in subjects with PD. Future studies with larger samples,
      inclusive of a higher volume of resistance exercise, are needed to extend these
      findings.

PMID- 18614957
TI  - Resistance training for medial compartment knee osteoarthritis and malalignment.
AB  - PURPOSES: 1) To evaluate the effects of a 12-wk high-intensity knee extensor and
      flexor resistance training program on strength, pain, and adherence in patients
      with advanced knee osteoarthritis and varus malalignment and 2) to generate pilot
      data for change in dynamic knee joint load, patent-reported outcomes, and self
      efficacy after training. METHODS: Fourteen patients (48.35 +/- 6.51 yr) with
      radiographically confirmed medial compartment knee osteoarthritis and varus
      malalignment of the lower limb were recruited from a surgical waiting list for
      high tibial osteotomy. Participants completed a high-intensity isokinetic
      resistance training program three times per week for 12 wk. Knee extensor and
      flexor strength were assessed every third week, whereas pain and adherence were
      recorded at every training session. The external knee adduction moment during the
      gait, the 6-min-walk test, the Knee Injury and Osteoarthritis Outcome Score
      (KOOS), and the Arthritis Self-Efficacy Scale (ASES) were also evaluated before
      and after training. RESULTS: Significant improvements in knee extensor and flexor
      strength were observed without increases in pain during or after training.
      Adherence to the high-intensity program was high. No significant changes were
      observed for dynamic knee joint load or the KOOS. There was a significant
      increase in the function subscale of the ASES only. CONCLUSIONS: These findings
      suggest that patients with advanced knee osteoarthritis and malalignment can
      experience substantial gains in strength after a high-intensity resistance
      training program without concomitant increases in pain, adverse events, or
      compromised adherence. These findings provide support for future clinical trials
      with longer-term outcomes.

PMID- 18614958
TI  - Temporal artery temperature measurements do not detect hyperthermic marathon
      runners.
AB  - INTRODUCTION: Exertional heat stroke is a cause of collapse in marathon runners.
      Rectal temperature (T(rectal)) measurement is the usual method of estimating core
      temperature in collapsed runners, and temporal artery thermometer (TAT)
      measurement is untested for field use in marathon runners and other athletes. The
      objective of this study is to compare TAT measurement with T(rectal) measurement
      in collapsed marathon runners. METHODS: TAT-500i (Exergen Corp, Wellesley, MA)
      temperature measurements were obtained using the manufacturer's instruction
      manual on 60 collapsed marathon runners who had T(rectal) measurements in the
      finish area medical tent during two consecutive annual races. RESULTS: The TAT
      temperatures identified only 2 of 17 hyperthermic runners (T(rectal) > 39.4
      degrees C (103 degrees F)), a sensitivity of only 0.12, and a Pearson'
      correlation coefficient of 0.374 (r = 0.14). Among the 17 hyperthermic runners,
      the correlation of T(rectal) to TAT temperatures was 0.526 (r = 0.28) with a mean
      +/- SD T(rectal) of 40.7 +/- 0.94 degrees C (105.1 +/- 1.7 degrees F) and a mean
      +/- SD TAT temperature of 37.4+/- 1.3 degrees C (99.4 +/- 2.4 degrees F). Among
      the 43 collapsed normothermic runners, there was no correlation between the
      rectal and the TAT measurements (r = -0.142, P = 0.37). CONCLUSIONS: These
      findings indicate that there is little association between the temperatures
      obtained by temporal artery measurement and T(rectal) measurement in collapsed
      marathon runners and that TAT temperature is unable to identify hyperthermic
      runners. Based on these findings, TAT measurement should not be used to assess
      core body temperature or make treatment decisions for marathon runners with
      potential exertional heat stroke.

PMID- 18614959
TI  - Predictive value of orthopedic evaluation and injury history at the NFL combine.
AB  - PURPOSE: The National Football League (NFL) holds an annual combine to evaluate
      college football athletes likely to be drafted for physical skills, to review
      their medical history, and to perform a physical examination. The athletes
      receive an orthopedic grade on their ability to participate in the NFL. The
      purpose of this study was to test the hypothesis that this orthopedic rating at
      the combine predicts the percent of athletes who play in the NFL and the length
      of their careers. METHODS: A database for all athletes reviewed at the combine by
      the medical staff of one team from 1987 to 2000 was created and linked to a data
      set containing the number of seasons and the games played in the NFL for each
      athlete. Players were grouped by orthopedic grade: high, low, and orthopedic
      failure. The percent of players who played in the NFL and the mean length of
      their careers was calculated and compared for these groups. RESULTS: The
      orthopedic grade assigned at the NFL combine correlated with the probability of
      playing in the league. Whereas 58% of athletes with a high grade and 55% of
      athletes with a low grade played at least one game, only 36% of athletes given a
      failing grade did so (P < 0.001). Players with a high grade had a mean career of
      41.5 games compared with 34.2 games for players with a low grade and 19.0 games
      for orthopedic failures. CONCLUSION: This is the first study to report on the
      predictive value of a grading system for college athletes before participation in
      professional sports. Other professional sports may benefit from using a similar
      grading system for the evaluation of potential players.

PMID- 18614960
TI  - Methicillin-resistant Staphylococcus aureus infections in collegiate football
      players.
AB  - PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) has been recognized
      as a serious skin infection in the athletic population. Literature in reference
      to football players has been sparse. We sought to better elucidate circumstances
      surrounding such infections in collegiate football players. METHODS: Data from
      three Division-I collegiate football programs were consolidated and analyzed.
      Variables included presence of MRSA infection, timing of occurrence, body
      location involved, lesion morphology, need for surgical treatment, and antibiotic
      route. Data were analyzed statistically to evaluate player position, body
      location, and timing of occurrences. RESULTS: Of the 491 collegiate football
      players, 33 (6.7%) were diagnosed with MRSA infections. Cutaneous manifestations
      included abscess (70%), cellulitis (16%), folliculitis, impetigo, and necrotizing
      fasciitis. Of the infections, 90% underwent surgical drainage, whereas 27%
      received intravenous antibiotics. Extremity infections (n = 30) greatly exceeded
      truncal infections (n = 7); the most common locations were the elbow (n = 11),
      knee (n = 6), leg (n = 4), and forearm (n = 4). There was no difference in
      occurrence by player position. Infections occurred predominantly in the first
      third of the season (P < 0.001, chi-square test) and significantly decreased as
      the season progressed. CONCLUSION: MRSA infections involving football players are
      becoming more common. This study documents player positions involved, timing of
      occurrence in the season, location and type of infections, and required
      treatment. Exposed extremities may predispose to infection due to risk for minor
      trauma and direct contact with bacteria. As infection risk seems to be
      independent of position, all players should observe protective measures. Although
      most infections occur earlier in the season, physicians should remain alert for
      infection occurrences throughout the season.

PMID- 18614961
TI  - Differentiation of RVOT-VT and ARVC in an elite athlete.
AB  - BACKGROUND: Differentiation of right ventricular outflow tract-ventricular
      tachycardia (RVOT-VT) and arrhythmogenic right ventricular cardiomyopathy (ARVC)
      can be problematic in athletes. The high incidence of sudden death as the first
      clinical manifestation in ARVC highlights the importance of correct diagnosis and
      treatment. We report on the case of RVOT-VT in an elite female sprinter, and we
      review the literature on ventricular tachycardia (VT) in the absence of
      structural heart disease and ARVC. DISCUSSION: Of patients who present with VT,
      10% have no obvious structural disease. In the case of idiopathic VT from the
      RVOT and LVOT, the arrhythmia is monomorphic and generally not familial. In both
      disorders, the resting ECG has no identifiable abnormalities, and the
      echocardiogram and coronary angiography are usually normal. ARVC is a heart
      muscle disorder characterized by structural and functional abnormalities of the
      right ventricle due to a fibro-fatty replacement of the myocardium. The natural
      history of ARVC is considered to include four distinct phases. The early
      concealed phase of ARVC demonstrates ECG abnormalities concomitant to right and
      left ventricular dyskinesias. Differential diagnosis during this phase is
      problematic due to the presence of left bundle branch block morphology VT
      together with ECG anomalies commonly observed in athletes in RVOT-VT.
      Furthermore, long-standing VT in RVOT-VT may result in ventricular wall motion
      abnormalities mimicking ARVC. Radiofrequency ablation may be a valuable tool in
      the differential diagnosis, because this technique is highly effective in the
      treatment of RVOT-VT and of limited value in ARVC. Continued follow-up evaluation
      is an important for the confirmation of disease status after the diagnosis of
      idiopathic RVOT-VT.

PMID- 18614962
TI  - Genetic risk factors of bronchopulmonary dysplasia.
AB  - The aim of the study was to assess the association between bronchopulmonary
      dysplasia (BPD) and polymorphisms of genes coding for vascular endothelial growth
      factor (VEGF), transforming growth factor (TGF-[beta]1), insulin-like growth
      factor (IGF-1), and 5,10-methylenetetrahydrofolate reductase (MTHFR). A sample of
      181 newborns with mean gestational age of 28 wk was prospectively evaluated.
      Molecular analysis of TGF-[beta]1 -800G>A, -509C>T, 10T>C, 25G>C, VEGF -460T>C
      and 405G>C and MTHFR 677C>T polymorphisms were performed and the number of CA
      repeats in the promoter region of IGF-1 gene was assessed. The frequency of all
      TGF-[beta]1, IGF-1, and MTHFR polymorphisms, as well as the frequency of VEGF
      405G>C polymorphism was similar in all groups. The newborns with -460TT and 
      460CT genotypes were significantly overrepresented in the BPD groups compared
      with the no BPD group. Multivariate analysis revealed that carrying T allele
      increased the risk of BPD by 9% (95%CI: 2-14%) above the baseline risk
      established for given gestational age, length of oxygen therapy, and sex. Based
      on our data from a single center, we propose that VEGF -460T>C polymorphism may
      influence the risk of BPD.

PMID- 18614963
TI  - A mouse model for juvenile doxorubicin-induced cardiac dysfunction.
AB  - Doxorubicin (DOX) is a potent antitumor agent. DOX can also induce
      cardiotoxicity, and high cumulative doses are associated with recalcitrant heart
      failure. Children are particularly sensitive to DOX-induced heart failure. The
      ability to genetically modify mice makes them an ideal experimental system to
      study the molecular basis of DOX-induced cardiotoxicity. However, most mouse DOX
      studies rely on acute drug administration in adult animals, which typically are
      analyzed within 1 wk. Here, we describe a juvenile mouse model of chronic DOX
      induced cardiac dysfunction. DOX treatment was initiated at 2 wk of age and
      continued for a period of 5 wk (25 mg/kg cumulative dose). This resulted in a
      decline in cardiac systolic function, which was accompanied by marked atrophy of
      the heart, low levels of cardiomyocyte apoptosis, and decreased growth velocity.
      Other animals were allowed to recover for 13 wk after the final DOX injection.
      Cardiac systolic function improved during this recovery period but remained
      depressed compared with the saline injected controls, despite the reversal of
      cardiac atrophy. Interestingly, increased levels of cardiomyocyte apoptosis and
      concomitant myocardial fibrosis were observed after DOX withdrawal. These data
      suggest that different mechanisms contribute to cardiac dysfunction during the
      treatment and recovery phases.

PMID- 18614965
TI  - Clinical, electrophysiological, and serum biochemical measures of progressive
      neurological and hepatic dysfunction in feline Niemann-Pick type C disease.
AB  - Niemann-Pick type C (NP-C) disease is a neurovisceral lysosomal storage disease
      characterized by neurologic dysfunction, hepatosplenomegaly, and early death.
      Natural history studies are very difficult to perform due to the low incidence
      and high heterogeneity of disease in the human population. Sixteen cats with a
      spontaneously occurring missense mutation in NPC1 were evaluated over time to
      define the progression of neurologic and hepatic disease. Affected cats had
      remarkably regular onsets of specific signs of cerebellar and vestibular system
      dysfunction with progressive severity of dysfunction quantified by postrotatory
      nystagmus and brain stem auditory evoked response measures. NP-C disease cats
      also showed increasing serum activity of alanine aminotransferase, asparate
      aminotransferase, and cholesterol with advancing age. Affected cats lived to a
      mean age of 20.5 +/- 4.8 wk. CNS and hepatic lesions were similar to those
      described in human patients. These data are the first to document progressive
      hepatic disease in the feline model and demonstrate the importance of liver
      disease as part of the NP-C disease phenotype. Both neurologic and hepatic
      measures of disease onset and severity can be used as a baseline with which to
      assess the efficacy of experimental therapies of NP-C disease in the feline
      model.

PMID- 18614964
TI  - Branched chain fatty acids are constituents of the normal healthy newborn
      gastrointestinal tract.
AB  - Vernix suspended in amniotic fluid is normally swallowed by the late term fetus.
      We hypothesized that branched chain fatty acids (BCFA), long known to be major
      vernix components, would be found in meconium and that the profiles would differ
      systematically. Vernix and meconium were collected from term newborns and
      analyzed. BCFA-containing lipids constituted about 12% of vernix dry weight, and
      were predominantly saturated, and had 11-26 carbons per BCFA. In contrast,
      meconium BCFA had 16-26 carbons, and were about 1% of dry weight. Meconium BCFA
      were mostly in the iso-configuration, whereas vernix BCFA contained dimethyl and
      middle chain branching, and five anteiso-BCFA. The mass of BCFA entering the
      fetal gut as swallowed vernix particles is estimated to be 180 mg in the last
      month of gestation whereas the total mass of BCFA found in meconium is estimated
      to be 16 mg, thus most BCFA disappear from the fetal gut. The BCFA profiles of
      vernix and meconium show that BCFA are major components of normal healthy term
      newborn gastrointestinal tract. BCFA are candidates for agents that play a role
      in gut colonization and should be considered a nutritional component for the
      fetus/newborn.

PMID- 18614966
TI  - Functional studies of the T295M mutation causing Glut1 deficiency: glucose efflux
      preferentially affected by T295M.
AB  - Glucose transporter type 1 (Glut1) deficiency syndrome (Glut1 DS, OMIM: #606777)
      is characterized by infantile seizures, acquired microcephaly, developmental
      delay, hypoglycorrhachia (CSF glucose <40 mg/dL), and decreased erythrocyte
      glucose uptake (56.1 +/- 17% of control). Previously, we reported two patients
      with a mild Glut1 deficiency phenotype associated with a heterozygous GLUT1 T295M
      mutation and normal erythrocyte glucose uptake. We assessed the pathogenicity of
      T295M in the Xenopus laevis oocyte expression system. Under zero-trans influx
      conditions, the T295M Vmax (590 pmol/min/oocyte) was 79% of the WT value and the
      Km (14.3 mM) was increased compared with WT (9.6 mM). Under zero-trans efflux
      conditions, both the Vmax (1216 pmol/min/oocyte) and Km (8.8 mM) in T295M mutant
      Glut1 were markedly decreased in comparison to the WT values (7443
      pmol/min/oocyte and 90.8 mM). Western blot analysis and confocal studies
      confirmed incorporation of the T295M mutant protein into the plasma membrane. The
      side chain of M295 is predicted to block the extracellular "gate" for glucose
      efflux in our Glut-1 molecular model. We conclude that the T295M mutation
      specifically alters Glut1 conformation and asymmetrically affects glucose flux
      across the cell by perturbing efflux more than influx. These findings explain the
      seemingly paradoxical findings of Glut1 DS with hypoglycorrhachia and "normal"
      erythrocyte glucose uptake.

PMID- 18614967
TI  - Role of microsomal prostaglandin E synthase-1 (mPGES1)-derived PGE2 in patency of
      the ductus arteriosus in the mouse.
AB  - Prostaglandin E2 (PGE2) plays a key role in the ductus arteriosus, prenatally by
      maintaining patency and postnatally by promoting tissue remodeling for closure.
      Here, by using near-term mouse fetuses with (wild-type, WT) and without
      microsomal PGE synthase-1 (mPGES1-/-), we have examined the importance of this
      enzyme for PGE2 formation and function. mPGES1-/- ductus, unlike WT ductus,
      contracted little, or not all, to indomethacin in vitro. Coincidentally, as
      evident from responses to NG-nitro-L-arginine methyl ester and zinc
      photoporphyrin, the mutant showed no significant enhancement of nitric oxide (NO)
      and carbon monoxide (CO)-based relaxation. mPGES1 suppression differs,
      therefore, from cyclooxygenase (COX) suppression, whether genetically or
      pharmacologically induced, where NO is markedly up-regulated. In vivo, the ductus
      was patent, albeit occasionally with a narrowed lumen, in all mPGES1-/- fetuses.
      Conversely, postnatal closure progressed regularly in mPGES1-/- animals thanks to
      residual PGE2 originating via mPGES2. We conclude that mPGES1 is critical for
      PGE2 formation in the ductus but its loss does not entail compensatory up
      regulation of other relaxing mechanisms. Accordingly, an mPGES1 inhibitor stands
      out as a prospective better tool, compared with the currently used COX
      inhibitors, for the management of premature infants with persistent ductus.

PMID- 18614968
TI  - Myocardial hypertrophy and the maturation of fatty acid oxidation in the newborn
      human heart.
AB  - After birth dramatic decreases in cardiac malonyl CoA levels result in the rapid
      maturation of fatty acid oxidation. We have previously demonstrated that the
      decrease in malonyl CoA is due to increased activity of malonyl CoA decarboxylase
      (MCD), and decreased activity of acetyl CoA carboxylase (ACC), enzymes which
      degrade and synthesize malonyl CoA, respectively. Decreased ACC activity
      corresponds to an increase in the activity of 5'-AMP activated protein kinase
      (AMPK), which phosphorylates and inhibits ACC. These alterations are delayed by
      myocardial hypertrophy. As rates of fatty acid oxidation can influence the
      ability of the heart to withstand an ischemic insult, we examined the expression
      of MCD, ACC, and AMPK in the newborn human heart. Ventricular biopsies were
      obtained from infants undergoing cardiac surgery. Immunoblot analysis showed a
      positive correlation between MCD expression and age. In contrast, a negative
      correlation in both ACC and AMPK expression and age was observed. All ventricular
      samples displayed some degree of hypertrophy, however, no differences in enzyme
      expression were found between moderate and severe hypertrophy. This indicates
      that increased expression of MCD, and the decreased expression of ACC and AMPK
      are important regulators of the maturation of fatty acid oxidation in the newborn
      human heart.

PMID- 18614969
TI  - [Differentiation of Staphylococcus aureus isolates based on phenotypical
      characters].
AB  - Typing of Staphylococcus aureus isolates is a necessary procedure for monitoring
      the transmission of S. aureus among carriers and in epidemiology. Evaluation of
      the range of relationship among isolates rely on epidemiological markers and is
      possible because of the clonal character of S. aureus species. Effective typing
      shows the scheme of transmission of infection in a selected area, enables
      identifying the reservoir of the microorganism, and may enhance effective
      eradication. A set of typing methods for use in analyses of epidemiological
      correlations and the identification of S. aureus isolates is presented. The
      following methods of typing are described: biotyping, serotyping, antibiogram,
      protein electrophoresis, cell protein profiles (proteom), immunoblotting,
      multilocus enzyme electrophoresis (MLEE), zymotyping, and standard species
      identification of S. aureus in the diagnostic laboratory. Phenotyping methods for
      S. aureus isolates used in the past and today in epidemiological investigations
      and in analyses of correlations among S. aureus isolates are presented in this
      review. The presented methods use morphological characteristics, physiological
      properties, and chemical structures of the bacteria as criteria for typing. The
      precision of these standard methods is not always satisfactory as S. aureus
      strains with atypical biochemical characters have evolved recently. Therefore it
      is essential to introduce additional typing procedures using molecular biology
      methods without neglecting phenotypic methods.

PMID- 18614970
TI  - [Metalloproteinases. Structure and function].
AB  - Matrix metalloproteinases (MMPs) belong to a large family of multidomain zinc
      endopeptidases. They are one of the most important proteolitic enzymes which
      digest components of the extracellular matrix and abundant macromolecules on cell
      surface and take part in many physiological processes, such as apoptosis or
      angiogenesis. MMPs are also engaged in the pathogenesis of many diseases such as
      arthritis and cancer. The development of effective inhibitors and discovery of
      their mechanisms of action can have significant influence on therapeutic
      strategy.

PMID- 18614971
TI  - Combined butyric acid/mesalazine treatment in ulcerative colitis with mild
      moderate activity. Results of a multicentre pilot study.
AB  - AIM: The short-chain fatty acid, acetate, propionate and butyrate are end
      products of fermentation by intestinal microflora of the indigestible material,
      mainly carbohydrates, reaching the colon and are essential for the vital function
      of the colonic cells. Butyric acid furnishes energy to the cells of the colon and
      may play an anti-inflammatory role in pathologies of large bowel. Low
      concentrations of butyrate and of short-chain fatty acids have been found in the
      colon of patients with ulcerative colitis and this may justify therapy with
      butyrate and mesalazine in this disease. The aim of the paper was to evaluate the
      efficacy of treatment with butyric acid and mesalazine in reducing relapse of
      mild to moderate ulcerative colitis in affected patients. METHODS: An open study
      was conducted by 19 Italian Gastrointestinal Units, forming part of the GISDI
      study Group, in 216 patients with ulcerative colitis who showed an incomplete
      response to standard mesalazine treatment. The treatment proposed is mesalazine
      (800 mg x3) + 3 butyrate 0.3 g + 0.250 inulin tablets, in a formulation resistant
      to intestinal absorption (ZACOL NMX, Bioactival). RESULTS: The results obtained
      indicate that the addition of 3 tablets/die of ZACOL-MNX is effective in reducing
      disease activity, with a marked improvement of symptoms and in the endoscopic
      appearance of mucosa. CONCLUSION: These findings prompt a further double-blind
      investigation to better define the efficacy of the proposed treatment.

PMID- 18614972
TI  - Use of corticosteroids, immunomodulators, and infliximab at a third-level Day
      Hospital Service of Gastro-Hepatology.
AB  - AIM: Third-level Day-Hospital Services of Gastro-Hepatology are likely to recruit
      patients with an increased disease severity. The burden of request for
      immunomodulation drugs is presently unclear. METHODS: The charts of 1 012
      consecutive patients who underwent day-hospital admission were reviewed. Among
      them, 975 were admitted for several reasons (percutaneous liver biopsies,
      abdominal fluid aspirations, infiltrations of hepatic nodules, gastrointestinal
      endoscopies with specific treatments). Data of the remaining 37 patients were
      elaborated. RESULTS: Of them, 31 (83%) suffered from ulcerative colitis (UC) or
      Crohn's disease (CD) (17 and 14, respectively) and 6 from autoimmune type 1
      hepatitis (AIH). Of the 14 non-operated UC patients, 12 were taking azathioprine
      (AZA) and 2 infliximab (IFX). Among CD patients, the majority received AZA (N=6)
      or IFX (N=6). Of the AIH patients, 5 were treated with AZA and 2 had also
      cyclosporine. Overall, corticosteroids (32%) and IFX (21%) ranked first and
      second among the induction drugs, and AZA ranked first (62%) as maintenance
      option. Of the 4 CD patients under IFX treatment, 2 were switched to
      leukapheresis for incomplete response, the third one developed thrombotic
      complications, and the last one achieved disease remission after 12 months. Of
      the 2 cases of UC, one lost response soon and was colectomized, the other is
      maintaining moderately active disease, requiring scheduled injections every 8
      weeks. CONCLUSION: Despite the caution imposed by the very small numbers, this
      analysis confirms that the potent available options are difficult to be correctly
      positioned in the therapeutic algorithm of inflammatory bowel disease.

PMID- 18614973
TI  - Evaluation of nutritional status and dietary intake in patients with advanced
      cancer on palliative care.
AB  - AIM: Cancer cachexia and malnutrition are very common in patients receiving
      palliative care. They cause a deterioration in the quality of life. METHODS: We
      studied 144 patients (52 females, 92 males) admitted to our Palliative Care Unit.
      Anthropometric measurements, food and nutritional intake, and plasma levels of
      few serum proteins were determined. Basal metabolic rate (BMR) was calculated.
      RESULTS: A body mass index (BMI) below 18.5 kg/m2 was observed in 23% of females
      and in 13% of males (P = NS). Twenty females (44%) and 52 males (63%) showed a
      weight loss of more than 10% over the 6-month period (P = 0.073). Ten females
      (19%) and 58 males (63%) had an arm muscle area (AMA) below the 5th percentile (P
      < 0.001), while 20 females (38%) and 21 males (23%) had an arm fat area (AFA)
      below the 5th percentile (P = 0.071). The daily calorie intake was below the BMR
      in 22 females (42%) and in 53 males (58%) (P = NS). Plasma levels of prealbumin,
      transferrin, and albumin were found below the normal range in more than 70% in
      both sexes. CONCLUSION: Protein energy malnutrition can be easily detected by
      anthropometric and laboratory indexes. The larger percentage of males with a
      reduction in lean body mass compared to females could signify an advantage for
      females since lean body mass is preserved for longer in them. Patients with
      advanced cancer receiving palliative care should thus be evaluated routinely to
      assess their nutritional status in order to plan an adequate nutritional program
      when appropriate.

PMID- 18614974
TI  - 2008 Clinical approach to irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS), as defined by Rome III diagnostic criteria,
      affects 10-20% of the general population, with women 20-40 years old accounting
      for the majority of patients. Although variable and intermittent, IBS symptoms
      may persist for many years. Repeated referrals for medical consultation and
      diagnostic studies generate huge healthcare costs. Since there is no evidence
      that IBS leads to more severe gastrointestinal disorders, in absence of alarm
      symptoms or signs, an invasive diagnostic algorithm is not indicated. Optimal
      treatment for IBS still needs to be defined. The clinical approach is based on
      treatment of the prevalent symptom. When pain predominates, antispasmodics are
      the first choice. In case of diarrhea, loperamide is useful for reducing bowel
      frequency. Soluble fiber represents the first option in subjects with IBS and
      constipation or mixed IBS. Dietary integrators composed of probiotics and
      serotonin precursors are a promising therapeutic option.

PMID- 18614975
TI  - Nephrotoxicity of intravenous immunoglobulin in the setting of liver
      transplantation or HBV-related cirrhosis: an undervalued topic.
AB  - It is well recognized that acute and/or chronic renal failure is a frequent
      complication after orthotopic liver transplantation (OLT). The multifactorial
      nature of the etiology of early as well as late renal failure in patients
      affected by HBV-related cirrhosis is not adequately appreciated by the transplant
      community, since renal dysfunction has mainly attributed to calcineurin inhibitor
      toxicity, alone or in combination with potentially nephrotoxic drugs. In the
      meanwhile the potential nephrotoxicity of some intravenous immunoglobulin (IVIg)
      preparations that more than other could affect the renal function was completely
      unattended. The use of polyvalent immunoglobulins has been associated in the past
      with several unresolved issues, including potential nephrotoxicity. Pathologic
      examination of the kidneys generally reveals changes typical of the osmotic
      nephrosis. The hypothesis of osmotic nephrosis is further supported by the fact
      that in most cases, acute renal failure has been associated, in the past, with
      the sucrose-containing IVIg products. In patients who underwent OLT for hepatitis
      B virus(HBV)-related liver disease the use of anti HBV immunoglobulins (HBIg) to
      avoid HBV-recurrence is highly effective and has really changed the outcome of
      this transplantation procedure. Nevertheless, the inappropriate use of HBIg could
      increase the risk of renal dysfunction, particularly in combination with
      nephrotoxic drugs.

PMID- 18614976
TI  - Achalasia.
AB  - Achalasia is a rare motor disorder of the esophagus, characterized by the absence
      of peristalsis and impaired swallow-induced relaxation. These motor abnormalities
      result in stasis of ingested food in the esophagus, leading to clinical symptoms,
      such as dysphagia, regurgitation of food, retrosternal pain and weight loss.
      Etiology is unknown. Some familial cases have been reported, but the rarity of
      familial occurrence does not support the hypothesis that genetic inheritance is a
      significant etiologic factor. Association of achalasia with viral infections and
      auto-antibodies against myenteric plexus has been reported, but the causal
      relationship remains unclear. In terms of diagnosis, esophageal manometry is the
      gold standard to diagnose achalasia. Still, its role in post-treatment
      surveillance remains controversial. Radiological studies support the initial
      diagnosis of achalasia and have been proposed for detecting preclinical
      symptomatic recurrence. Although endoscopy is considered to have a poor
      sensitivity and specificity in the diagnosis of achalasia, it has an important
      role in ruling out secondary causes of achalasia. Treatment is strictly
      palliative. Current medical and surgical therapeutic options (pneumatic dilation,
      surgical myotomy, and pharmacologic agents) aimed at reducing the lower
      esophageal sphincter (LES) pressure and facilitating esophageal emptying by
      gravity and hydrostatic pressure of retained food and liquids.

PMID- 18614977
TI  - New insights into Lactobacillus and functional intestinal disorders.
AB  - Intestinal microflora can be considered as a ''dynamic system'' that actively
      interacts with the intestinal epithelium and the local immune system. It
      synthesizes antimicrobial substances (bacteriocins), vitamins (PP, B1, B6, B12),
      it produces a major intestinal nutrient (butyric acid) and interacts in a
      competitive fashion with the pathogens. Lactobacilli concentration (Gram+, Gram
      variable, facultative anaerobes) is generally decreased in irritable bowel
      syndrome (IBS) patients. This syndrome has, until recently been considered to be
      ''functional'', whereas, in fact, it may result from previous enteritis (in up to
      31% of patients), featuring a persistent low-grade intestinal inflammation and a
      reduction in interleukin-10 (IL-10) concentration. Some Lactobacilli strains
      (e.g. L. paracasei subsp. paracasei) in vitro lead to normalisation of the
      hypercontractility of the smooth muscle cells. A growing body of clinical
      findings indicates that some ''genetically stable'' strains of Lactobacilli may
      be useful in the treatment, even long term, of IBS, and reduce the postoperative
      infection rate, especially in critically ill patients (orthotopic liver
      transplant, severe pancreatitis). However, some Lactobacilli, ''not genetically
      stable'', used in the treatment of neutropenic patients during chemotherapy and
      in pediatric patients submitted to gastrojejunostomy, have been reported to lead
      to bacteremia and endocarditis. These effects may be due to transfer of bacteria
      and genetic material. Therefore, the confirmed genetic stability and the fact
      that no antibiotic resistance occurs are fundamental requisites for the use of
      Lactobacilli in certain disorders of the gastrointestinal tract, such as, for
      instance, IBS. In conclusion, ''genetically stable'' Lactobacilli (L. paracasei
      subsp. Paracasei F19) have recently become available, representing an exiting new
      field in clinical studies and for treatment purposes, offering guarantees of
      safety also for long-term use. Careful personalized evaluation, as always in
      medical practice, is necessary in order to gain further insight into, and to
      validate with additional studies, the role of ''genetically stable'' Lactobacilli
      in the treatment of IBS.

PMID- 18614978
TI  - Nutritional assessment of elderly people.
AB  - Since today's society is characterised by an increase in the number of elderly
      persons, who are subject more than any other group to an alteration in their
      state of nutrition, in this review we propose the possible methods that can be
      used for an accurate nutritional diagnosis in this age group. Considering that
      malnutrition, sarcopenia and motor disability are factors that are more likely to
      occur with aging, it is extremely important for certain clinical anamnestic
      parameters, such as biohumoral and anthropometric indicators, but also specific
      tables and questionnaires, to become standard routine practice in health care in
      order to facilitate the diagnosis of these possible events.

PMID- 18614979
TI  - Ciprofloxacin-induced acute cholestatic liver injury and associated renal
      failure. Case report and review.
AB  - Ciprofloxacin, a commonly prescribed fluoroquinolone antibiotic, has generally
      been well-tolerated; however, there are rare reports of associated hepatic
      failure or renal failure. We describe a case of a 65 year-old man with a history
      of ischemic cardiomyopathy who was treated with ciprofloxacin 500 mg twice daily
      for cellulitis. Six days into his treatment course, he developed acute
      cholestatic jaundice and acute anuric renal failure. Clinical, laboratory, and
      pathologic data suggest that the patient had developed reversible, severe
      ciprofloxacin-induced cholestatic liver injury and acute tubular necrosis
      requiring hemodialysis. Within two months of stopping the ciprofloxacin, the
      patient was off dialysis and back to his baseline creatinine in three months.
      Liver tests normalized by five months. This report illustrates a case of
      cholestatic liver injury and renal failure involving ciprofloxacin use. We review
      the literature regarding hepatic and renal injury as it relates to ciprofloxacin.
      To our knowledge, this represents the first case report of simultaneous acute
      cholestatic liver injury and renal failure secondary to ciprofloxacin.

PMID- 18614980
TI  - A case of infectious esophagitis caused by human papilloma virus.
AB  - Esophageal infections may be caused by diverse pathogens that alter the mucosal
      lining and produce mild symptoms or sometimes critical clinical diseases with a
      high risk of mortality, particularly among the immunocompromised. The most common
      causes of infectious esophagitis are: herpes virus, candida, cytomegalovirus
      (CMV), and human immunodeficiency virus (HIV); human papilloma virus (HPV)
      infections are rare in Western countries. Endoscopic features of infectious
      esophagitis are specific for different agents; nonetheless, differential
      diagnosis is difficult and requires biopsy, cultures and brushing. We present the
      clinical case of a young woman admitted to the Department of General Surgery of
      A.O.U. Federico II, Naples, for a large, deep ulcerative lesion of the esophagus
      caused by HPV infection.

PMID- 18614981
TI  - Temporal trends in baseline characteristics and peri-procedural complications of
      percutaneous drug-eluting stent implantation for unprotected left main disease: a
      single high-volume center experience.
AB  - AIM: Percutaneous drug-eluting stent (DES) implantation is commonly used in
      patients with unprotected left main (ULM) disease. As this procedure has been
      performed routinely in Turin Center since 2002, this article aimed to summarize a
      five year-experience in DES implantation in the ULM. METHODS: Baseline,
      procedural and in-hospital outcome data of all patients with ULM undergoing
      percutaneous coronary intervention (PCI) with DES between July 2002 and October
      2006 at Turin Center have been collected. Patients were randomized into four
      groups: A (patients treated between July 2002 and December 2003), B (treated in
      2004), C (treated in 2005) and D (treated in 2006). The baseline surgical risk
      features was to be compared with the European System for Cardiac Operative Risk
      Evaluation, disease location in the ULM, and in-hospital major adverse cerebro
      cardiovascular events (MACCE), defined as death, myocardial infarction, repeat
      percutaneous revascularization, coronary artery bypass grafting, stroke, or stent
      thrombosis. RESULTS: Out of a total of 4 432 coronary interventional procedures
      198 patients treated with DES in the ULM were identified. There was a significant
      increase in the number of patients treated (P=0.00095), but no difference in
      EuroSCORE across groups (P=0.14). Conversely, there was a significant temporal
      trend in the incidence of bifurcational ULM being treated with DES (P=0.03).
      Intriguingly, despite this increase in adverse lesion characteristics, no
      significant increase was found in the rate of in-hospital MACCE (P=0.93).
      CONCLUSION: In this single-center study, the number of patients being treated
      with DES for ULM disease has risen across the years, although keeping a similar
      surgical risk profile. Distal ULM involvement is no longer considered an absolute
      contraindication to PCI, as testified by the increasing frequency of such lesion
      among patients undergoing DES implantation at this Institution, with remarkably
      low rates of adverse events.

PMID- 18614982
TI  - The long QT syndrome in pediatric age: prognosis and risk factor.
AB  - AIM: Long QT syndrome is a rare arrhythmic disease with a low incidence in the
      general population. There are no sure clinical or electrocardiographic parameters
      that could lead to a correct prognostic stratification in patients affected by
      this syndrome. The correlation between the incidence of a sudden death or
      dangerous ventricular arrhythmias and the duration of QTc interval is still a
      controversial topic. METHODS: Twenty nine children affected by QT long syndrome
      were admitted to the Division of Pediatric Cardiology of the Casa del Sole
      Hospital of Palermo (Italy). Their diagnosis was made by electrocardiogram (ECG).
      The average age of the patients was 7.6 years. The average follow-up was 4 years
      and three months. A therapy with beta-blocker was administered to all the
      children. During the follow-up of 4 year and three months, patients were
      genotyped. Twenty-three out of 29 children had at least one relative affected by
      the syndrome. Three of them had a familiar dead because of this syndrome and
      everyone had a duration of maximum QTc higher than the cut off (P=0.0002). All
      the people who died had not followed the therapy with beta-blocker. Patients with
      a maximum QTc recorded <500 had not familiar death by this syndrome. RESULTS:
      Holter and echocardiogram recorded periodically during the observation did not
      show dangerous arrhythmic events. All children maintained a good health during
      the follow-up. CONCLUSION: Although conducted on a small study population, the
      data analysis recorded during this study suggests that in patients affected by QT
      long syndrome younger than 16 years old undergoing a beta-blocker therapy the
      prognosis is excellent. The duration of QTc interval appears as a negative
      prognostic factor, although the beta-blocker therapy has been reduced
      considerably the incidence of sudden death.

PMID- 18614983
TI  - Use of Impella Recover 2.5 left ventricular assist device in patients with
      cardiogenic shock or undergoing high-risk percutaneous coronary intervention
      procedures: experience of a high-volume center.
AB  - AIM: Percutaneous coronary interventions are increasingly applied to high-risk
      patients. The availability of hemodynamic support devices offers a promising
      option to prevent and treat low-output syndrome in these patients. The aim of
      this study was to evaluate the feasibility, safety and efficacy of the Impella
      Recover'' LP 2.5 left ventricular assist device in patients with cardiogenic
      shock or undergoing high-risk percutaneous coronary interventions. METHODS:
      Eleven patients presenting cardiogenic shock (N=6) or scheduled for high-risk
      percutaneous revascularization (N=5) were evaluated. The Impella pump was
      successfully implanted in all patients, except one. When implanted, the device
      was correctly positioned in the left ventricle and remained in a stable position.
      RESULTS: Bleedings occurred in 7 patients (5 of them presented cardiogenic
      shock), while renal failure and severe thrombocytopenia were observed in 4 and 1
      patients respectively, all with cardiogenic shock. During high-risk procedures,
      the Impella pump succeeded in obtaining hemodynamic stability, while in only two
      patients with cardiogenic shock the device determined a significant improvement
      of hemodynamic variables. All elective patients and two patients with cardiogenic
      shock were discharged from the hospital and were still alive at 30-day follow-up.
      CONCLUSION: These data, although preliminary due to the limited sample size,
      demonstrated the feasibility, safety and efficacy of the Impella Recover LP 2.5
      during high-risk percutaneous procedures, even though the benefits of
      prophylactic deployment of such a system have to be further investigated. The use
      of Impella Recover LP 2.5 in patients with cardiogenic shock is feasible and
      safe, however it maybe insufficient in reversing an advanced cardiogenic shock
      which, probably, has to be treated with more powerful left ventricular assist
      devices.

PMID- 18614984
TI  - Experimental-clinical study on the effects of hydromassage with Thermae Oasis's
      salsobromoiodine water in chronic venous stasis disease of the lower extremities.
AB  - AIM: The aim of this study was to evaluate the efficacy of thermal therapy, in
      particular hydromassage therapy with the ''Ca' Rossa'' salsobromoiodic water of
      the Thermae Oasis (Ferrara, Italy), in patients with chronic venous insufficiency
      (CVI) of the inferior limbs. METHODS: Fourty-four patients with primary varices
      of the legs were enrolled. The anamnestic symptomatologic indicators of disease
      were: pain, perception of heaviness or paresthesias, nocturnal cramps, ''restless
      leg'' syndrome, pruritus. The symptoms were evaluated for both intensity and
      frequency. An additional clinical indicator was the centimetric measurement of
      the leg diameters at 3 levels: supramalleolar, mid-calf and mid-thigh. The
      patients were subdivided in two groups: patients submitted to a cycle of
      hydromassage with salsobromoiodic water and patients treated with compressive
      elastic stocking (12 mmHg). At the end of the treatment cycle, symptomatologic
      and clinical data were reassessed, in addition to morphological and velocimetric
      parameters related to the function of the peripheral vascular system. RESULTS:
      The results showed in Group A (thermal water hydromassage) an improved reduction
      of subjective and objective symptoms as compared to the control Group B,
      demonstrating a superior efficacy of thermal therapy. CONCLUSION: The efficacy of
      hydromassage therapy is due not only to the favourable action of hydrostatic
      pressure upon venous flow of the inferior limbs, but also to the peculiar
      chemical and physical characteristics of the thermal water utilized in this
      study. The elevated osmotic power of hydromassage is responsible for the
      significant intrinsic antiedematous properties.

PMID- 18614985
TI  - Proteases and chronic leg ulcers.
AB  - AIM: The aim of this study was to compare the effect of cadexomer on reducing
      wound surface area of leg ulcers compared to that obtained in a group patients
      whose ulcers were treated by compression therapy. METHODS: For each ulcer group,
      wound surface area was calculated at day 0 and after 28 days of treatment: this
      allowed to calculate the average wound surface area reduction, the percent
      reduction in wound size, as well as the weekly wound size reduction index.
      RESULTS: In the cadexomer-treated ulcers the total wound area reduction was 9.67
      cm(2)/week, with a weekly wound size reduction index per patient of 0.96 cm(2);
      in the controls (compression therapy-treated patients) the total wound area
      reduction was 6.11 cm(2)/week, with a weekly reduction index per patient of 0.61
      cm(2). At the end of treatment, in the group of patients whose ulcers were
      treated with cadexomer ointment the average wound size reduction was 43%, whereas
      in the control-treated patient group the average wound size reduction was 28%.
      CONCLUSION: These data suggest that cadexomer can play an important role in the
      healing of chronic leg ulcers.

PMID- 18614986
TI  - Cardiovascular autonomic neuropathy in HIV-positive African patients.
AB  - AIM: HIV infection causes cardiac autonomic neuropathy (CAN); little is known
      about the relevance of CAN in sub-Sahara African patients, in spite of the
      highest prevalence of AIDS in that population. The authors assessed prevalence
      rates of CAN in HIV-positive treatment-naive African patients and investigated
      the correlation between degree of immunodeficiency and CAN. METHODS: Thirty HIV
      positive patients and 11 HIV-negative controls underwent a battery of
      cardiovascular autonomic function tests; the Ewing-Clarke score was calculated
      along with the stage of severity of CAN. The patients' immunological status was
      evaluated by CD4 T-lymphocytes counts. RESULTS: During paced respiration of
      normal depth, the patients showed shorter baseline RR intervals (739.2+/-136.0 vs
      846.2+/-88.7 ms; P<0.05), with an inverse correlation with CD4 counts, and lower
      heart rate variability (85.3+/-73.0 vs 123.0+/-46.2 ms; P<0.02). Although
      patients with lower CD4 counts tended to present blunted response to hand-grip
      and cold-face tests, no linear correlation was found between results of
      cardiovascular reflex tests and CD4 counts. Eight patients (27%) obtained
      borderline Ewing-Clarke scores; 9 patients resulted affected by early (6 pts,
      20%) or intermediate (3 pts, 10%) stage of CAN. CONCLUSION: Signs of HIV-related
      CAN are present in 30% of the African HIV+ patients observed, with no direct
      correlation to their immunological status. Based on the relevance of the problem
      and the presence of signs of CAN even in newly diagnosed and treatment-naive
      patients, the authors suggest that all HIV-patients should be screened for the
      presence of the complication, in view of the possible serious events associated
      with it.

PMID- 18614987
TI  - Volatile anesthetics for periprocedural cardiac protection. A review.
AB  - All volatile anesthetics have cardiac depressant effects that decrease myocardial
      oxygen demand and may, therefore, have a beneficial role on the myocardial oxygen
      balance during ischemia. Recently, experimental evidence has clearly demonstrated
      that in addition to these indirect protective effects, volatile anesthetic agents
      also have direct protective properties against ischemic myocardial damage. The
      implementation of these properties during clinical anesthesia can provide an
      additional tool in the treatment or prevention, or both, of ischemic cardiac
      dysfunction in the perioperative period. A recent meta-analysis showed that
      desflurane and sevoflurane reduce postoperative mortality and incidence of
      myocardial infarction following cardiac surgery with significant advantages in
      terms of postoperative cardiac troponin release, need for inotrope support, time
      on mechanical ventilation, intensive care unit and overall hospital stay.
      Multicenter, randomized clinical trials had previously demonstrated that the use
      of desflurane can reduce the postoperative release of cardiac troponin I, the
      need for inotropic support, and the number of patients requiring prolonged
      hospitalization, following coronary artery bypass graft surgery, either with and
      without cardiopulmonary bypass. Evidence in non-coronary surgical settings is
      contradictory and will be reviewed in this paper together with the mechanism of
      cardiac protection by volatile agents.

PMID- 18614988
TI  - Thrombolytic treatment of acute myocardial infarction in the presence of
      ventricular paced rhythm.
AB  - Usually, therapeutic decisions in patients with acute chest pain are based on the
      12-lead electrocardiogram because ST-segment elevation is highly specific for
      myocardial infarction, but the presence of pacing-induced repolarization changes
      makes electrocardiogram interpretation difficult. The authors report an acute
      myocardial infarction patient with ventricular paced rhythm successfully treated
      by thrombolytic therapy. The aim of this work aims to highlight the difficulty
      with electrocardiographic diagnosis and timely treatment of myocardial infarction
      in the presence of ventricular pacing.

PMID- 18614989
TI  - Double access technique for left anterior descending PTCA in a mammary graft
      recipient.

PMID- 18614990
TI  - Growth hormone deficiency and increased coronary risk.

PMID- 18614991
TI  - Populations receiving optimally fluoridated public drinking water--United States,
      1992-2006.
AB  - Water fluoridation has been identified by CDC as one of 10 great public health
      achievements of the 20th century. The decline in the prevalence and severity of
      dental caries (tooth decay) in the United States during the past 60 years has
      been attributed largely to the increased use of fluoride. Community water
      fluoridation is an equitable and cost-effective method for delivering fluoride to
      the community. A Healthy People 2010 objective is to increase to 75% the
      proportion of the U.S. population served by community water systems who receive
      optimally fluoridated water. To update and revise previous reports on
      fluoridation in the United States and describe progress toward the Healthy People
      2010 objective, CDC analyzed fluoridation data for the period 1992-2006 from the
      50 states and District of Columbia (DC). The results indicated that the
      percentage of the U.S. population served by community water systems who received
      optimally fluoridated water increased from 62.1% in 1992, to 65.0% in 2000, and
      69.2% in 2006, and those percentages varied substantially by state. Public health
      officials and policymakers in states with lower percentages of residents
      receiving optimal water fluoridation should consider increasing their efforts to
      promote fluoridation of community water systems to prevent dental caries.

PMID- 18614992
TI  - Monitoring health effects of wildfires using the biosense system--San Diego
      County, California, October 2007.
AB  - During October 21-26, 2007, wildfires consumed hundreds of thousands of acres and
      forced the evacuation of more than 300,000 persons in San Diego County,
      California. During large-scale emergencies, data are needed to assess health
      effects, plan response, and evaluate response adequacy. This report describes
      some of the health effects of the wildfires based on data from the CDC BioSense
      system, which receives emergency department (ED) patient chief complaint
      information and physician diagnosis codes from six hospitals in San Diego County.
      Analysis of these data indicated that ED visits for respiratory disease,
      especially those associated with dyspnea and asthma, increased during a 5-day
      fire period compared with the preceding 20 weekdays. For the six hospitals
      combined, visits for dyspnea increased from 48.6 to 72.6 per day, and visits with
      diagnoses of asthma increased from 21.7 to 40.4 per day. Local, state, and
      federal public health personnel should continue collaborative efforts to expand
      and

PMID- 18614993
TI  - Disparities in secondhand smoke exposure--United States, 1988-1994 and 1999-2004.
AB  - No level of exposure to secondhand smoke (SHS) is safe. Breathing SHS can cause
      heart disease and lung cancer in nonsmoking adults and increases the risk for
      sudden infant death syndrome, acute respiratory infections, middle-ear disease,
      and exacerbation of asthma in children. In the United States, exposure to SHS
      declined approximately 70% from the late 1980s through 2002, most likely
      reflecting widespread implementation of laws and policies prohibiting smoking in
      indoor workplaces and public places during this period. Although the major
      sources of SHS exposure for nonsmoking adults are the home and workplace, the
      primary source of SHS exposure for children is the home; therefore, eliminating
      smoking in workplaces and public places is less likely to reduce children's
      exposure to SHS. This report examines changes in the prevalence of self-reported
      SHS exposure at home and changes in any exposure, as measured by serum cotinine
      (a biologic indicator of SHS exposure), in nonsmoking children, adolescents, and
      adults. The analysis was conducted using data from the 1988-1994 and 1999-2004
      National Health and Nutrition Examination Surveys (NHANES). The results indicated
      that self-reported SHS exposure at home and SHS exposure as measured by serum
      cotinine declined significantly (i.e., by 51.2% and 44.7%, respectively) in the
      U.S. population from 1988-1994 to 1999-2004; however, the decline was smaller for
      persons aged 4-11 years and 12-19 years. These results underscore the need to
      continue surveillance of SHS exposure and to focus on strategies to reduce
      children's SHS exposure.

PMID- 18614994
TI  - Integrins mediate adherence and migration of T lymphocytes on human peritoneal
      mesothelial cells.
AB  - We previously showed that a local immune response largely composed of type 1 T
      cells correlated with a favorable outcome of the peritonitis associated with
      peritoneal dialysis. To clarify how these subsets are recruited to the peritoneal
      cavity during inflammation, we measured integrin-mediated interactions between
      the T cells and human peritoneal mesothelial cells. Direct microscopy showed that
      lipopolysaccharide or peritoneal dialysis effluent stimulated the adherence of T
      cells to mesothelial cells, a process mediated by the integrins alpha6beta1 and
      alpha4beta1. Further, the migration of Th1 cell across human mesothelial cell
      monolayers grown on transwell surfaces was reduced by anti-alpha6beta1 integrin
      antibody while that of Th2 cell was inhibited by an anti-alpha4 integrin
      antibody. Pretreatment with either lipopolysaccharide or rapid response
      peritoneal dialysis effluent stimulated T cell migration and this was
      significantly decreased by the alpha6beta1 compared to the alpha4 antibody. These
      results suggest that integrins may play an important role in mediating selective
      T cell subset adhesion and migration across human peritoneal mesothelial cell
      monolayers and differential integrin expression and selective T cell subset
      recruitment during peritonitis may affect outcome.

PMID- 18614995
TI  - Differential distribution of the Sodium-vitamin C cotransporter-1 along the
      proximal tubule of the mouse and human kidney.
AB  - Vitamin C is reabsorbed from the renal lumen by one isoform of sodium-vitamin C
      co-transporters that mediate high affinity sodium-dependent L-ascorbic acid
      transport. Sodium-vitamin C cotransporter-1 mRNA has been detected in intestine
      and liver and the S3 segment of the renal proximal tubule. Here, we found that
      its distribution was broader and all three proximal tubule segments of mouse and
      human expressed the transporter but the S3 segment had the highest expression.
      Sodium-vitamin C co-transporter-1 expression was also found in the renal
      epithelial-derived LLC-PK1 cell line. Ascorbic acid transport in these cells was
      regulated by a single kinetic component that depended on the sodium
      concentration, pH and temperature. Reducing ascorbate concentration increased the
      apical expression of the transporter suggesting the presence of a feedback system
      for regulation of transporter abundance at the luminal membrane.

PMID- 18614996
TI  - The aging kidney.
AB  - Renal aging, by itself, is associated with alterations in renal morphology and a
      decline in renal function, which is accelerated and/or accentuated by diseases
      such as diabetes mellitus and hypertension. The aging-related renal insufficiency
      has important implications with regards to body homeostasis, drug toxicity, and
      renal transplantation. An understanding of renal aging and its distinction from
      renal insufficiency secondary to diseases is essential for individualized care of
      the elderly. Toward this end, investigations are underway to elucidate the
      molecular mechanisms of renal aging. This review summarizes the structural and
      functional changes of the aging kidney and highlights the advances made in our
      understanding of the renal aging process.

PMID- 18614997
TI  - High osmolality induces the kidney-specific chloride channel CLC-K1 by a serum
      and glucocorticoid-inducible kinase 1 MAPK pathway.
AB  - The kidney-specific chloride channels CLC-K1/2 and their functionally important
      subunit barttin, by mediating solute transport in medulla, contribute to the
      osmotic gradient. We sought to determine whether they themselves are regulated by
      variations of osmolality. The expression of CLC-K1 and barttin mRNA and protein
      was significantly increased in a distal convoluted tubule cell line after a shift
      to high osmolar medium. This upregulation paralleled that of serum and
      glucocorticoid-inducible kinase 1 (SGK1), a gene known to be upregulated by cell
      shrinkage. Specific knockdown of SGK1 or addition of the p38 MAPK pathway
      inhibitor SB203580 abolished the induction of SGK1, CLC-K1 and barttin by high
      osmolarity suggesting that a functional MAPK pathway is required to mediate
      osmotic-driven induction of all three genes. The physiological relevance of our
      in vitro data was confirmed by water deprivation of male C57BL6 mice, which
      caused a significant increase in serum osmolality along with induction of CLC-K1,
      barttin and SGK1. Our study shows that change in intracellular volume, because of
      high osmolality, result in SGK1 upregulation and the subsequent increase of CLC
      K1/barttin expression in distal renal tubular cells in vivo and in vitro.

PMID- 18614998
TI  - Antiretroviral therapy improves renal function among HIV-infected Ugandans.
AB  - Renal dysfunction is a severe complication of advanced HIV disease. We evaluated
      the impact of highly active antiretroviral therapy (HAART) on renal function
      among HIV-infected Ugandans in the Home-Based AIDS Care clinical trial. The
      patients presented with symptomatic HIV disease or CD4 cell count < or = 250
      cells/mm(3) and creatinine clearances above 25 ml/min determined by the Cockcroft
      Gault equation. Of the 508 patients at baseline, 8% had a serum creatinine over
      133 micromol/l and about 20% had reduced renal function evidenced by a creatinine
      clearance between 25 and 50 ml/min. After 2 years of HAART, the median serum
      creatinine was significantly decreased by 16% while the median creatinine
      clearance significantly increased 21%. The median creatinine clearance of
      patients with renal dysfunction at baseline, increased by 53% during 2 years of
      treatment. In multivariable analysis, a baseline creatinine above 133 micromol/l,
      a weight gain of more than 5 kg over the 2 years, female gender and a WHO stage 4
      classification were all associated with greater improvements in creatinine
      clearance on HAART. Our study shows that renal dysfunction was common with
      advanced HIV disease in Uganda but this improved following 2 years of HAART.

PMID- 18615000
TI  - Expansion of cytolytic CD4+CD28- T cells in end-stage renal disease.
AB  - Cytomegalovirus (CMV) seropositivity is associated with increased risk for
      atherosclerotic disease in patients with end-stage renal disease. This
      association is due to a unique peripheral blood CD4(+) T cell population which
      lack CD28 (CD4(+)CD28(-) T cells). Here we found that this patient population has
      a significant age-dependent increase of CD4(+)CD28(-) T cells that comprise over
      half of the circulating CD4 T cells in some. Patients over 50 years of age have a
      50-fold higher percentage of CD4(+)CD28(-) T cells compared to seronegative
      patients and a 5-fold higher percentage when compared to seropositive healthy
      controls. Stimulation by CMV-antigen or by polyclonal stimulation using PMA and
      ionomycin showed that CD4(+)CD28(-) cells in patients with end stage renal
      disease degranulated and secreted interferon gamma thus indicating that they are
      cytolytic. The average anti-CMV IgG titer displayed a remarkable age-dependent
      increase only in patients with end stage renal disease. These findings are highly
      suggestive of repetitive antigenic stimulation of the immune system in patients
      with end stage disease by subclinical CMV reactivation which might contribute to
      increased atherosclerotic risk.

PMID- 18614999
TI  - HIV-1 Vpr inhibits cytokinesis in human proximal tubule cells.
AB  - Transgenic mouse models of HIV-associated nephropathy (HIVAN) show that
      expression of HIV-1 genes in kidney cells produces collapsing focal segmental
      glomerulosclerosis and microcystic tubular disease typical of the human disease.
      HIV-1 vpr plays an important role in the glomerulosclerosis of HIVAN, especially
      when it is associated with nef expression in podocytes. Further, Vpr is reported
      to exacerbate tubular pathology. Here we determined effects of vpr expression on
      renal tubular epithelial cell function by transducing them with a pseudotyped
      lentivirus vector carrying HIV-1 vpr and control genes. Vpr expression in the
      cultured cells impaired cytokinesis causing cell enlargement and multinucleation.
      This profound in vitro phenotype caused us to reexamine the HIVAN mouse model and
      human HIVAN biopsies to see if similar changes occur in vivo. Both showed
      abundant hypertrophic tubule cells similar to the in vitro finding that
      represents a previously unappreciated aspect of the human disease. Additionally,
      multinucleated tubular cells were identified in the murine HIVAN model and
      increased chromosome number was detected in tubular cells of human HIVAN
      biopsies. Our study provides evidence of a new clinical phenotype in HIVAN that
      may result from the ability of Vpr to impair cytokinesis.

PMID- 18615001
TI  - A case of nephrocalcinosis.

PMID- 18615002
TI  - The role of ethnicity in variability in response to drugs: focus on clinical
      pharmacology studies.
AB  - Ethnicity is one factor that may account for the observed differences in both
      pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, resulting in
      variability in response to drug therapy. Given that the applicability of clinical
      study results to the treatment of an individual patient is a critical
      consideration in a physician's choice of drug therapy, drug development should
      seek to ensure that a clinical pharmacologic evaluation includes a population
      that is representative of the target therapeutic population. Ethnic diversity in
      drug response with respect to safety and efficacy and the resulting differences
      in recommended doses have been well described for some drugs. Some of these
      differential responses may be related to the pharmacogenomics of a particular
      drug. Pharmacogenomic techniques have recently enjoyed widespread use in studies
      of drug exposure and response. The clinical relevance of variability in drug
      response due to pharmacogenomics of drug-metabolizing enzymes was considered at a
      September 2004 workshop cosponsored by the US Food and Drug Administration (FDA),
      Johns Hopkins University, and the Pharmaceutical Research and Manufacturers of
      America (http://www.fda.gov/cder/Offices/OCPB/workshops.htm).

PMID- 18615003
TI  - Lack of evidence for an effect of lopinavir/ritonavir on tenofovir renal
      clearance.

PMID- 18615005
TI  - Finding the right research question: quality science depends on quality careers.
AB  - When making the transition from trainee to principal investigator, there are few
      steps more important than selecting the first independent research project. The
      project must synthesize the excitement and idealism of contributing to the well
      being of humankind and the practical realities of an area of inquiry that is
      likely to lead to a successful career.

PMID- 18615004
TI  - beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes
      in hypertension.
AB  - Numerous studies have demonstrated that beta(1)- and beta(2)-adrenergic receptor
      gene (ADRB1 and ADRB2) variants influence cardiovascular risk and beta-blocker
      responses in hypertension and heart failure. We evaluated the relationship
      between ADRB1 and ADRB2 haplotypes, cardiovascular risk (death, nonfatal
      myocardial infarction (MI), and nonfatal stroke), and atenolol-based vs.
      verapamil sustained-release (SR)-based antihypertensive therapy in 5,895 coronary
      artery disease (CAD) patients. After an average of 2.8 years, death rates were
      higher in patients carrying the ADRB1 Ser49-Arg389 haplotype (hazard ratio (HR)
      3.66, 95% confidence interval (95% CI) 1.68-7.99). This mortality risk was
      significant in patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06
      35.8) but not atenolol (HR 2.31, 95% CI 0.82-6.55), suggesting a protective role
      for the beta-blocker. ADRB2 haplotype associations were divergent within the
      treatment groups but did not remain significant after adjustment for multiple
      comparisons. ADRB1 haplotype variation is associated with mortality risk, and
      beta-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2
      polymorphisms.

PMID- 18615006
TI  - Availability and choice of antimalarials at medicine outlets in Ghana: the
      question of access to effective medicines for malaria control.
AB  - Although national and international efforts to combat malaria have intensified
      over the years, problems with availability, distribution, and choice of
      antimalarials at medicine outlets in Africa continue to exist. This article
      presents the results of an indicator-based assessment of availability and choice
      of antimalarials at 130 licensed medicine outlets in Ghana. We also discuss how
      the choice of an antimalarial to dispense conforms to recommendations of the
      national policy for malaria therapy. Data were obtained through face-to-face
      interviews, by reviewing facility records, and by observing the practices of
      dispensing staff in the medicine outlets. Antimalarials recommended in the policy
      were not readily available in the most accessible medicine outlets. Few outlets
      adhered to the policy when choosing antimalarials. Interventions targeting
      medicine outlets should be initiated to improve availability and access to
      effective medicines in order to support the national program for malaria control.

PMID- 18615007
TI  - Identification of information flow-modulating drug targets: a novel bridging
      paradigm for drug discovery.
AB  - Our objective in this study was to identify novel metrics for efficient
      identification of drug targets using biological network topology data. We
      developed a novel paradigm and metric, namely, bridging centrality, capable of
      identifying nodes critically involved in connecting or bridging modular
      subregions of a network. The topological and biological characteristics of
      bridging nodes were delineated in a diverse group of published yeast networks and
      in three human networks: those involved in cardiac arrest, C21-steroid hormone
      biosynthesis, and steroid biosynthesis. The bridging centrality metric was highly
      selective for bridging nodes. Bridging nodes differed distinctively from nodes
      with high degree and betweenness centrality. Bridging nodes had lower lethality,
      and their gene expression was consistent with independent regulation. Analysis of
      biological correlates indicated that bridging nodes are promising drug targets
      from the standpoints of efficacy and side effects. The bridging centrality method
      is a promising computational systems biology tool to aid target identification in
      drug discovery.

PMID- 18615010
TI  - Early parental deprivation in the marmoset monkey produces long-term changes in
      hippocampal expression of genes involved in synaptic plasticity and implicated in
      mood disorder.
AB  - In mood disorder, early stressors including parental separation are vulnerability
      factors, and hippocampal involvement is prominent. In common marmoset monkeys,
      daily parental deprivation during infancy produces a prodepressive state of
      increased basal activity and reactivity in stress systems and mild anhedonia that
      persists at least to adolescence. Here we examined the expression of eight genes,
      each implicated in neural plasticity and in the pathophysiology of mood disorder,
      in the hippocampus of these same adolescent marmosets, relative to their normally
      reared sibling controls. We also measured hippocampal volume. Early deprivation
      led to decreases in hippocampal growth-associated protein-43 (GAP-43) mRNA,
      serotonin 1A receptor (5-HT(1A)R) mRNA and binding ([3H]WAY100635), and to
      increased vesicular GABA transporter mRNA. Brain-derived neurotrophic factor
      (BDNF), synaptophysin, vesicular glutamate transporter 1 (VGluT1), microtubule
      associated protein-2, and spinophilin transcripts were unchanged. There were some
      correlations with in vivo biochemical and behavioral indices, including VGluT1
      mRNA with reward-seeking behavior, and serotonin 1A receptor mRNA with CSF
      cortisol. Early deprivation did not affect hippocampal volume. We conclude that
      early deprivation in a nonhuman primate, in the absence of subsequent stressors,
      has a long-term effect on the hippocampal expression of genes implicated in
      synaptic function and plasticity. The reductions in GAP-43 and serotonin 1A
      receptor expressions are comparable with findings in mood disorder, supporting
      the possibility that the latter reflect an early developmental contribution to
      disease vulnerability. Equally, the negative results suggest that other features
      of mood disorder, such as decreased hippocampal volume and BDNF expression, are
      related to different aspects of the pathophysiological process.

PMID- 18615011
TI  - Tiagabine increases [11C]flumazenil binding in cortical brain regions in healthy
      control subjects.
AB  - Accumulating evidence indicates that synchronization of cortical neuronal
      activity at gamma-band frequencies is important for various types of perceptual
      and cognitive processes and that GABA-A receptor-mediated transmission is
      required for the induction of these network oscillations. In turn, the
      abnormalities in GABA transmission postulated to play a role in psychiatric
      conditions such as schizophrenia might contribute to the cognitive deficits seen
      in this illness. We measured the ability to increase GABA in eight healthy
      subjects by comparing the binding of [(11)C]flumazenil, a positron emission
      tomography (PET) radiotracer specific for the benzodiazepine (BDZ) site, at
      baseline and in the presence of an acute elevation in GABA levels through the
      blockade of the GABA membrane transporter (GAT1). Preclinical work suggests that
      increased GABA levels enhance the affinity of GABA-A receptors for BDZ ligands
      (termed 'GABA shift'). Theoretically, such an increase in the affinity of GABA-A
      receptors should be detected as an increase in the binding of a GABA-A BDZ
      receptor site-specific PET radioligand. GAT1 blockade resulted in significant
      increases in mean (+/- SD) [(11)C]flumazenil-binding potential (BP(ND)) over
      baseline in brain regions representing the major functional domains of the
      cerebral cortex: association cortex +15.2+/-20.2% (p=0.05), sensory cortex
      +13.5+/-15.5% (p=0.03) and limbic (medial temporal lobe, MTL) +16.4+/-20.2%
      (p=0.03). The increase in [(11)C]flumazenil-BP(ND) was not accounted for by
      differences in the plasma-free fraction (f(P); paired t-test p=0.24) or changes
      in the nonspecific binding (pons V(T), p=0.73). Moreover, the ability to increase
      GABA strongly predicted (r=0.85, p=0.015) the ability to entrain cortical
      networks, measured through EEG gamma synchrony during a cognitive control task in
      these same subjects. Although additional studies are necessary to further
      validate this technique, these data provide preliminary evidence of the ability
      to measure in vivo, with PET, acute fluctuations in extracellular GABA levels and
      provide the first in vivo documentation of a relationship between GABA
      neurotransmission and EEG gamma-band power in humans.

PMID- 18615012
TI  - Diffusion tensor tractography in mesencephalic bundles: relation to mental
      flexibility in detoxified alcohol-dependent subjects.
AB  - Components of the corticocerebellar circuit and the midbrain individually play a
      central role in addictive processes and have been associated with altered volumes
      and impairment of cognitive flexibility in alcohol-dependent subjects. The
      microstructure of white matter bundles composing the corticocerebellar network
      and passing through the midbrain was studied using diffusion tensor imaging in a
      group of detoxified alcohol-dependent men (n=20) and a group of healthy men
      (n=24). The relationship between properties of these white matter bundles and
      cognitive flexibility performance was investigated in alcohol-dependent subjects.
      Bundles connecting two regions of interest were analyzed using a fiber-tracking
      quantitative approach, which provided estimates of the fractional anisotropy and
      the apparent diffusion coefficient, as well as the number of tracked fibers
      normalized by the volume of regions of interest. Within the bundles running
      between the midbrain and pons, a mean of 18% fewer fibers per unit volume were
      tracked in alcohol-dependent men than in healthy controls. In addition, the
      normalized number of these fibers correlated with the performance in the Trail
      Making Test part-B. Even though the alcohol-dependent subjects were detoxified
      and apparently neurologically intact, their earlier excessive use of alcohol
      seems to be associated with altered neural microstructure of mesencephalic white
      matter bundles, which may contribute to their cognitive flexibility impairment.

PMID- 18615013
TI  - Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery.
AB  - Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple
      aspects of the cell division process. Activation of PLK1 requires phosphorylation
      of a conserved threonine residue (Thr 210) in the T-loop of the PLK1 kinase
      domain, but the kinase responsible for this has not yet been affirmatively
      identified. Here we show that in human cells PLK1 activation occurs several hours
      before entry into mitosis, and requires aurora A (AURKA, also known as STK6)
      dependent phosphorylation of Thr 210. We find that aurora A can directly
      phosphorylate PLK1 on Thr 210, and that activity of aurora A towards PLK1 is
      greatly enhanced by Bora (also known as C13orf34 and FLJ22624), a known cofactor
      for aurora A (ref. 7). We show that Bora/aurora-A-dependent phosphorylation is a
      prerequisite for PLK1 to promote mitotic entry after a checkpoint-dependent
      arrest. Importantly, expression of a PLK1-T210D phospho-mimicking mutant
      partially overcomes the requirement for aurora A in checkpoint recovery. Taken
      together, these data demonstrate that the initial activation of PLK1 is a primary
      function of aurora A.

PMID- 18615014
TI  - Amygdala intercalated neurons are required for expression of fear extinction.
AB  - Congruent findings from studies of fear learning in animals and humans indicate
      that research on the circuits mediating fear constitutes our best hope of
      understanding human anxiety disorders. In mammals, repeated presentations of a
      conditioned stimulus that was previously paired to a noxious stimulus leads to
      the gradual disappearance of conditioned fear responses. Although much evidence
      suggests that this extinction process depends on plastic events in the amygdala,
      the underlying mechanisms remain unclear. Intercalated (ITC) amygdala neurons
      constitute probable mediators of extinction because they receive information
      about the conditioned stimulus from the basolateral amygdala (BLA), and
      contribute inhibitory projections to the central nucleus (CEA), the main output
      station of the amygdala for conditioned fear responses. Thus, after extinction
      training, ITC cells could reduce the impact of conditioned-stimulus-related BLA
      inputs to the CEA by means of feed-forward inhibition. Here we test the
      hypothesis that ITC neurons mediate extinction by lesioning them with a toxin
      that selectively targets cells expressing micro-opioid receptors (microORs).
      Electron microscopic observations revealed that the incidence of microOR
      immunoreactive synapses is much higher in ITC cell clusters than in the BLA or
      CEA and that microORs typically have a post-synaptic location in ITC cells. In
      keeping with this, bilateral infusions of the microOR agonist dermorphin
      conjugated to the toxin saporin in the vicinity of ITC neurons caused a 34%
      reduction in the number of ITC cells but no significant cell loss in surrounding
      nuclei. Moreover, ITC lesions caused a marked deficit in the expression of
      extinction that correlated negatively with the number of surviving ITC neurons
      but not CEA cells. Because ITC cells exhibit an unusual pattern of receptor
      expression, these findings open new avenues for the treatment of anxiety
      disorders.

PMID- 18615015
TI  - Switching on and off fear by distinct neuronal circuits.
AB  - Switching between exploratory and defensive behaviour is fundamental to survival
      of many animals, but how this transition is achieved by specific neuronal
      circuits is not known. Here, using the converse behavioural states of fear
      extinction and its context-dependent renewal as a model in mice, we show that bi
      directional transitions between states of high and low fear are triggered by a
      rapid switch in the balance of activity between two distinct populations of basal
      amygdala neurons. These two populations are integrated into discrete neuronal
      circuits differentially connected with the hippocampus and the medial prefrontal
      cortex. Targeted and reversible neuronal inactivation of the basal amygdala
      prevents behavioural changes without affecting memory or expression of behaviour.
      Our findings indicate that switching between distinct behavioural states can be
      triggered by selective activation of specific neuronal circuits integrating
      sensory and contextual information. These observations provide a new framework
      for understanding context-dependent changes of fear behaviour.

PMID- 18615016
TI  - Drosophila RNAi screen identifies host genes important for influenza virus
      replication.
AB  - All viruses rely on host cell proteins and their associated mechanisms to
      complete the viral life cycle. Identifying the host molecules that participate in
      each step of virus replication could provide valuable new targets for antiviral
      therapy, but this goal may take several decades to achieve with conventional
      forward genetic screening methods and mammalian cell cultures. Here we describe a
      novel genome-wide RNA interference (RNAi) screen in Drosophila that can be used
      to identify host genes important for influenza virus replication. After modifying
      influenza virus to allow infection of Drosophila cells and detection of influenza
      virus gene expression, we tested an RNAi library against 13,071 genes (90% of the
      Drosophila genome), identifying over 100 for which suppression in Drosophila
      cells significantly inhibited or stimulated reporter gene (Renilla luciferase)
      expression from an influenza-virus-derived vector. The relevance of these
      findings to influenza virus infection of mammalian cells is illustrated for a
      subset of the Drosophila genes identified; that is, for three implicated
      Drosophila genes, the corresponding human homologues ATP6V0D1, COX6A1 and NXF1
      are shown to have key functions in the replication of H5N1 and H1N1 influenza A
      viruses, but not vesicular stomatitis virus or vaccinia virus, in human HEK 293
      cells. Thus, we have demonstrated the feasibility of using genome-wide RNAi
      screens in Drosophila to identify previously unrecognized host proteins that are
      required for influenza virus replication. This could accelerate the development
      of new classes of antiviral drugs for chemoprophylaxis and treatment, which are
      urgently needed given the obstacles to rapid development of an effective vaccine
      against pandemic influenza and the probable emergence of strains resistant to
      available drugs.

PMID- 18615017
TI  - High-resolution mapping of meiotic crossovers and non-crossovers in yeast.
AB  - Meiotic recombination has a central role in the evolution of sexually reproducing
      organisms. The two recombination outcomes, crossover and non-crossover, increase
      genetic diversity, but have the potential to homogenize alleles by gene
      conversion. Whereas crossover rates vary considerably across the genome, non
      crossovers and gene conversions have only been identified in a handful of loci.
      To examine recombination genome wide and at high spatial resolution, we generated
      maps of crossovers, crossover-associated gene conversion and non-crossover gene
      conversion using dense genetic marker data collected from all four products of
      fifty-six yeast (Saccharomyces cerevisiae) meioses. Our maps reveal differences
      in the distributions of crossovers and non-crossovers, showing more regions where
      either crossovers or non-crossovers are favoured than expected by chance.
      Furthermore, we detect evidence for interference between crossovers and non
      crossovers, a phenomenon previously only known to occur between crossovers. Up to
      1% of the genome of each meiotic product is subject to gene conversion in a
      single meiosis, with detectable bias towards GC nucleotides. To our knowledge the
      maps represent the first high-resolution, genome-wide characterization of the
      multiple outcomes of recombination in any organism. In addition, because non
      crossover hotspots create holes of reduced linkage within haplotype blocks, our
      results stress the need to incorporate non-crossovers into genetic linkage
      analysis.

PMID- 18615018
TI  - Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza
      H5N1 virus.
AB  - The recent emergence of highly pathogenic avian influenza A virus strains with
      subtype H5N1 pose a global threat to human health. Elucidation of the underlying
      mechanisms of viral replication is critical for development of anti-influenza
      virus drugs. The influenza RNA-dependent RNA polymerase (RdRp) heterotrimer has
      crucial roles in viral RNA replication and transcription. It contains three
      proteins: PA, PB1 and PB2. PB1 harbours polymerase and endonuclease activities
      and PB2 is responsible for cap binding; PA is implicated in RNA replication and
      proteolytic activity, although its function is less clearly defined. Here we
      report the 2.9 angstrom structure of avian H5N1 influenza A virus PA (PA(C),
      residues 257-716) in complex with the PA-binding region of PB1 (PB1(N), residues
      1-25). PA(C) has a fold resembling a dragon's head with PB1(N) clamped into its
      open 'jaws'. PB1(N) is a known inhibitor that blocks assembly of the polymerase
      heterotrimer and abolishes viral replication. Our structure provides details for
      the binding of PB1(N) to PA(C) at the atomic level, demonstrating a potential
      target for novel anti-influenza therapeutics. We also discuss a potential
      nucleotide binding site and the roles of some known residues involved in
      polymerase activity. Furthermore, to explore the role of PA in viral replication
      and transcription, we propose a model for the influenza RdRp heterotrimer by
      comparing PA(C) with the lambda3 reovirus polymerase structure, and docking the
      PA(C) structure into an available low resolution electron microscopy map.

PMID- 18615019
TI  - A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA.
AB  - Structured RNAs embedded in the untranslated regions (UTRs) of messenger RNAs can
      regulate gene expression. In bacteria, control of a metabolite gene is mediated
      by the self-cleaving activity of a ribozyme embedded in its 5' UTR. This
      discovery has raised the question of whether gene-regulating ribozymes also exist
      in eukaryotic mRNAs. Here we show that highly active hammerhead ribozymes are
      present in the 3' UTRs of rodent C-type lectin type II (Clec2) genes. Using a
      hammerhead RNA motif search with relaxed delimitation of the non-conserved
      regions, we detected ribozyme sequences in which the invariant regions, in
      contrast to the previously identified continuous hammerheads, occur as two
      fragments separated by hundreds of nucleotides. Notably, a fragment pair can
      assemble to form an active hammerhead ribozyme structure between the translation
      termination and the polyadenylation signals within the 3' UTR. We demonstrate
      that this hammerhead structure can self-cleave both in vitro and in vivo, and is
      able to reduce protein expression in mouse cells. These results indicate that an
      unrecognized mechanism of post-transcriptional gene regulation involving
      association of discontinuous ribozyme sequences within an mRNA may be modulating
      the expression of several CLEC2 proteins that function in bone remodelling and
      the immune response of several mammals.

PMID- 18615020
TI  - Do female hyaenas choose mates based on tenure?
AB  - In their investigation into whether female mate-choice drives male dispersal,
      Honer et al. argue that female spotted hyaenas (Crocuta crocuta) prefer mates
      whose tenure in the social group is less than the females' age, to avoid paternal
      incest, and suggest that male dispersal reflects this preference. However, we are
      not persuaded that females choose mates on the basis of tenure because Honer et
      al. overlook the alternative hypothesis that dispersal status itself is important
      in female mate-choice, such that females prefer immigrants over natal males. Like
      mate-choice based on tenure, choice based on dispersal status reduces the risk of
      incest.

PMID- 18615025
TI  - An unnecessary battle.

PMID- 18615026
TI  - The long war against flu.

PMID- 18615027
TI  - A social contract.

PMID- 18615034
TI  - A biologist despairs over the difficulty of demonstrating heritability of
      chromatin states.

PMID- 18615039
TI  - Leaders still vague on emissions targets.

PMID- 18615040
TI  - Scientists rally to Mexican researchers' plea.

PMID- 18615041
TI  - Researcher battles CNRS reforms.

PMID- 18615042
TI  - When there's no room to grow.

PMID- 18615044
TI  - A Spanish revival. Cristina Garmendia interviewed by Cristina Jimenez.

PMID- 18615045
TI  - Super-sensitive tool key to dark-matter claim.

PMID- 18615046
TI  - Shock tactics point to risk after quake.

PMID- 18615047
TI  - Boyz 2 pipettemen.

PMID- 18615055
TI  - Archaeology: The lost world.

PMID- 18615056
TI  - Psychiatric genetics: The brains of the family.

PMID- 18615057
TI  - Genetic testing must recognize impact of bad news on recipient.

PMID- 18615058
TI  - Future of open access could be online and peer-reviewed.

PMID- 18615059
TI  - International law should govern release of GM mosquitoes.

PMID- 18615061
TI  - Cuddly animals don't persuade poor people to back conservation.

PMID- 18615062
TI  - Action needed to prevent extinctions caused by disease.

PMID- 18615063
TI  - The contents of the syringe.

PMID- 18615064
TI  - Ready for avian flu?

PMID- 18615070
TI  - Behind the looking-glass.

PMID- 18615071
TI  - Palaeontology: Squint of the fossil flatfish.

PMID- 18615072
TI  - Planetary science: The early Moon was rich in water.

PMID- 18615075
TI  - Asteroids: How to make a flying saucer.

PMID- 18615074
TI  - Cancer: An unexpected addiction.

PMID- 18615076
TI  - Solid-state chemistry: New order for lithium bromide.

PMID- 18615078
TI  - Rotational breakup as the origin of small binary asteroids.
AB  - Asteroids with satellites are observed throughout the Solar System, from
      subkilometre near-Earth asteroid pairs to systems of large and distant bodies in
      the Kuiper belt. The smallest and closest systems are found among the near-Earth
      and small inner main-belt asteroids, which typically have rapidly rotating
      primaries and close secondaries on circular orbits. About 15 per cent of near
      Earth and main-belt asteroids with diameters under 10 km have satellites. The
      mechanism that forms such similar binaries in these two dynamically different
      populations was hitherto unclear. Here we show that these binaries are created by
      the slow spinup of a 'rubble pile' asteroid by means of the thermal YORP
      (Yarkovsky-O'Keefe-Radzievskii-Paddack) effect. We find that mass shed from the
      equator of a critically spinning body accretes into a satellite if the material
      is collisionally dissipative and the primary maintains a low equatorial
      elongation. The satellite forms mostly from material originating near the
      primary's surface and enters into a close, low-eccentricity orbit. The properties
      of binaries produced by our model match those currently observed in the small
      near-Earth and main-belt asteroid populations, including 1999 KW(4) (refs 3, 4).

PMID- 18615077
TI  - Structure of the Ebola virus glycoprotein bound to an antibody from a human
      survivor.
AB  - Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate
      attachment and fusion of viral and host membranes. Here we report the crystal
      structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to
      a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit
      outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled
      by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like
      domain restrict access to the conserved receptor-binding site sequestered in the
      chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion
      and may explain why survivors have insignificant neutralizing antibody titres.
      KZ52 recognizes a protein epitope at the chalice base where it clamps several
      regions of the pre-fusion GP2 to the amino terminus of GP1. This structure
      provides a template for unravelling the mechanism of EBOV GP-mediated fusion and
      for future immunotherapeutic development.

PMID- 18615079
TI  - Volatile content of lunar volcanic glasses and the presence of water in the
      Moon's interior.
AB  - The Moon is generally thought to have formed and evolved through a single or a
      series of catastrophic heating events, during which most of the highly volatile
      elements were lost. Hydrogen, being the lightest element, is believed to have
      been completely lost during this period. Here we make use of considerable
      advances in secondary ion mass spectrometry to obtain improved limits on the
      indigenous volatile (CO(2), H(2)O, F, S and Cl) contents of the most primitive
      basalts in the Moon-the lunar volcanic glasses. Although the pre-eruptive water
      content of the lunar volcanic glasses cannot be precisely constrained, numerical
      modelling of diffusive degassing of the very-low-Ti glasses provides a best
      estimate of 745 p.p.m. water, with a minimum of 260 p.p.m. at the 95 per cent
      confidence level. Our results indicate that, contrary to prevailing ideas, the
      bulk Moon might not be entirely depleted in highly volatile elements, including
      water. Thus, the presence of water must be considered in models constraining the
      Moon's formation and its thermal and chemical evolution.

PMID- 18615080
TI  - Quadrupole transitions revealed by Borrmann spectroscopy.
AB  - The Borrmann effect-a dramatic increase in transparency to X-ray beams-is
      observed when X-rays satisfying Bragg's law diffract through a perfect crystal.
      The minimization of absorption seen in the Borrmann effect has been explained by
      noting that the electric field of the X-ray beam approaches zero amplitude at the
      crystal planes, thus avoiding the atoms. Here we show experimentally that under
      conditions of absorption suppression, the weaker electric quadrupole absorption
      transitions are effectively enhanced to such a degree that they can dominate the
      absorption spectrum. This effect can be exploited as an atomic spectroscopy
      technique; we show that quadrupole transitions give rise to additional structure
      at the L(1), L(2) and L(3) absorption edges of gadolinium in gadolinium gallium
      garnet, which mark the onset of excitations from 2s, 2p(1/2) and 2p(3/2) atomic
      core levels, respectively. Although the Borrmann effect served to underpin the
      development of the theory of X-ray diffraction, this is potentially the most
      important experimental application of the phenomenon since its first observation
      seven decades ago. Identifying quadrupole features in X-ray absorption
      spectroscopy is central to the interpretation of 'pre-edge' spectra, which are
      often taken to be indicators of local symmetry, valence and atomic environment.
      Quadrupolar absorption isolates states of different symmetries to that of the
      dominant dipole spectrum, and typically reveals orbitals that dominate the
      electronic ground-state properties of lanthanides and 3d transition metals,
      including magnetism. Results from our Borrmann spectroscopy technique feed into
      contemporary discussions regarding resonant X-ray diffraction and the nature of
      pre-edge lines identified by inelastic X-ray scattering. Furthermore, because the
      Borrmann effect has been observed in photonic materials, it seems likely that the
      quadrupole enhancement reported here will play an important role in modern
      optics.

PMID- 18615081
TI  - A multi-component Fermi surface in the vortex state of an underdoped high-Tc
      superconductor.
AB  - To understand the origin of superconductivity, it is crucial to ascertain the
      nature and origin of the primary carriers available to participate in pairing.
      Recent quantum oscillation experiments on high-transition-temperature (high-T(c))
      copper oxide superconductors have revealed the existence of a Fermi surface akin
      to that in normal metals, comprising fermionic carriers that undergo orbital
      quantization. The unexpectedly small size of the observed carrier pocket,
      however, leaves open a variety of possibilities for the existence or form of any
      underlying magnetic order, and its relation to d-wave superconductivity. Here we
      report experiments on quantum oscillations in the magnetization (the de Haas-van
      Alphen effect) in superconducting YBa(2)Cu(3)O(6.51) that reveal more than one
      carrier pocket. In particular, we find evidence for the existence of a much
      larger pocket of heavier mass carriers playing a thermodynamically dominant role
      in this hole-doped superconductor. Importantly, characteristics of the multiple
      pockets within this more complete Fermi surface impose constraints on the
      wavevector of any underlying order and the location of the carriers in momentum
      space. These constraints enable us to construct a possible density-wave model
      with spiral or related modulated magnetic order, consistent with experimental
      observations.

PMID- 18615082
TI  - Preseismic velocity changes observed from active source monitoring at the
      Parkfield SAFOD drill site.
AB  - Measuring stress changes within seismically active fault zones has been a long
      sought goal of seismology. One approach is to exploit the stress dependence of
      seismic wave velocity, and we have investigated this in an active source cross
      well experiment at the San Andreas Fault Observatory at Depth (SAFOD) drill site.
      Here we show that stress changes are indeed measurable using this technique. Over
      a two-month period, we observed an excellent anti-correlation between changes in
      the time required for a shear wave to travel through the rock along a fixed
      pathway (a few microseconds) and variations in barometric pressure. We also
      observed two large excursions in the travel-time data that are coincident with
      two earthquakes that are among those predicted to produce the largest coseismic
      stress changes at SAFOD. The two excursions started approximately 10 and 2 hours
      before the events, respectively, suggesting that they may be related to pre
      rupture stress induced changes in crack properties, as observed in early
      laboratory studies.

PMID- 18615083
TI  - The evolutionary origin of flatfish asymmetry.
AB  - All adult flatfishes (Pleuronectiformes), including the gastronomically familiar
      plaice, sole, turbot and halibut, have highly asymmetrical skulls, with both eyes
      placed on one side of the head. This arrangement, one of the most extraordinary
      anatomical specializations among vertebrates, arises through migration of one eye
      during late larval development. Although the transformation of symmetrical larvae
      into asymmetrical juveniles is well documented, the evolutionary origins of
      flatfish asymmetry are uncertain because there are no transitional forms linking
      flatfishes with their symmetrical relatives. The supposed inviability of such
      intermediates gave pleuronectiforms a prominent role in evolutionary debates,
      leading to attacks on natural selection and arguments for saltatory change. Here
      I show that Amphistium and the new genus Heteronectes, both extinct spiny-finned
      fishes from the Eocene epoch of Europe, are the most primitive pleuronectiforms
      known. The orbital region of the skull in both taxa is strongly asymmetrical, as
      in living flatfishes, but these genera retain many primitive characters unknown
      in extant forms. Most remarkably, orbital migration was incomplete in Amphistium
      and Heteronectes, with eyes remaining on opposite sides of the head in post
      metamorphic individuals. This condition is intermediate between that in living
      pleuronectiforms and the arrangement found in other fishes. Amphistium and
      Heteronectes indicate that the evolution of the profound cranial asymmetry of
      extant flatfishes was gradual in nature.

PMID- 18615084
TI  - Social diversity promotes the emergence of cooperation in public goods games.
AB  - Humans often cooperate in public goods games and situations ranging from family
      issues to global warming. However, evolutionary game theory predicts that the
      temptation to forgo the public good mostly wins over collective cooperative
      action, and this is often also seen in economic experiments. Here we show how
      social diversity provides an escape from this apparent paradox. Up to now,
      individuals have been treated as equivalent in all respects, in sharp contrast
      with real-life situations, where diversity is ubiquitous. We introduce social
      diversity by means of heterogeneous graphs and show that cooperation is promoted
      by the diversity associated with the number and size of the public goods game in
      which each individual participates and with the individual contribution to each
      such game. When social ties follow a scale-free distribution, cooperation is
      enhanced whenever all individuals are expected to contribute a fixed amount
      irrespective of the plethora of public goods games in which they engage. Our
      results may help to explain the emergence of cooperation in the absence of
      mechanisms based on individual reputation and punishment. Combining social
      diversity with reputation and punishment will provide instrumental clues on the
      self-organization of social communities and their economical implications.

PMID- 18615088
TI  - Growth and neurodevelopment at 16 to 24 months of age for infants born with
      gastroschisis.
AB  - OBJECTIVE: To examine growth, neurodevelopment and morbidity in infants with
      gastroschisis. STUDY DESIGN: We enrolled all infants with gastroschisis treated
      at the North Carolina Children's Hospital from March 2003 through June 2005.
      Neonatal data were collected. Medical history, growth and neurodevelopment were
      assessed at 16 to 24 months. RESULT: Of 24 infants, 17 completed follow-up.
      Weight and length were below the 10th percentile for five and six infants,
      respectively. Three infants scored less than 85 on the Bayley Scales of Infant
      Development, second edition. Small for gestational age (SGA) infants were smaller
      and had lower neurodevelopmental scores. Fourteen experienced continued bowel
      dysfunction; nine were rehospitalized. CONCLUSION: One-third of infants with
      gastroschisis experience growth delay. Infants who are SGA are at higher risk,
      suggesting that postnatal growth may be influenced by fetal phenomena, and may
      not be modifiable. Neurodevelopment is not delayed. Continued bowel dysfunction
      is common.

PMID- 18615090
TI  - Increased carotid artery intima-media thickness following venoarterial
      extracorporeal membrane oxygenation in the neonatal period.
AB  - OBJECTIVE: To compare left carotid intima-media thickness (CIMT) and biochemical
      markers for atherogenesis in neonatal venoarterial extracorporeal membrane
      oxygenation (ECMO) survivors with normal controls during childhood. METHODS:
      Venoarterial ECMO survivors and healthy patients between 12 and 18 years of age
      were enrolled in a matched control prospective study. ECMO survivors were matched
      to controls based on chronological age and percentage of body mass index (BMI).
      Measured CIMT of the posterior left carotid artery and CIMT values corrected for
      carotid artery size were used for data analysis. RESULTS: Thirty-one neonatal
      venoarterial ECMO survivors were matched to 31 healthy controls. No significant
      differences were found between ECMO survivors and controls for age, weight,
      percentage of BMI, total fat composition, lipid profiles, ultrasensitive C
      reactive protein or homocysteine levels. Significant differences between ECMO and
      controls patients were found in systolic, diastolic and mean left CIMT.
      CONCLUSION: Compared with controls, the thickness of the left carotid intima
      media is significantly increased at the age of 12 to 18 years in neonatal
      venoarterial ECMO survivors. The clinical significance of this increased CIMT is
      unknown. ECMO centers may want to incorporate assessment of CIMT in their follow
      up protocols.

PMID- 18615091
TI  - Postoperative cardiorespiratory instability following ligation of the preterm
      ductus arteriosus is related to early need for intervention.
AB  - OBJECTIVE: To investigate the effect of postnatal age at patent ductus arteriosus
      (PDA) ligation on postoperative need for cardiotropic support. STUDY DESIGN: A
      significant proportion of premature infants with a hemodynamically significant
      ductus arteriosus (HSDA) require surgical intervention. The relationship of
      postnatal maturation to postoperative cardiorespiratory stability is poorly
      understood. All preterm neonates who underwent PDA ligation between October 2002
      and September 2004 were identified and divided according to postnatal age at
      ductal ligation, into early (<or=4 weeks, n=29) and late (>4 weeks, n=36) groups.
      Neonatal birth demographics and morbidities, characteristics of the HSDA and
      reason for ligation were reviewed. Indices of cardiorespiratory stability (for
      example heart rate, mean arterial pressure) were recorded before and 1, 4, 8, 12
      and 24 h following ligation. Details of perioperative cardiovascular
      interventions (for example crystalloid boluses, cardiotropic agents) were
      recorded. RESULT: There were no differences in baseline neonatal demographics
      between the groups although a greater number of babies requiring early ligation
      had contraindication to indomethacin as the main reason for ligation. Early PDA
      ligation was associated with increased postoperative cardiotrope requirement
      (27.6 vs 5.6%, P=0.02) and decreased systolic blood pressure 8 h after
      intervention (P<0.05). Although increased oxygenation index was observed in both
      groups during the first 12 h it was only sustained to 24 h in the early group
      (P<0.05). Age at ligation remained a significant risk factor for postoperative
      cardiotrope requirement on multiple logistic regression analysis. CONCLUSION:
      Surgical ligation of the ductus arteriosus in preterm infants less than 28 days
      old is associated with oxygenation difficulties, decreased systolic arterial
      pressure and an increased need for cardiotropic support in the initial 24
      postoperative hours. These data suggest the need to prospectively characterize
      perioperative cardiovascular physiology and identify predictive factors of
      clinical deterioration.

PMID- 18615089
TI  - Can magnetic resonance spectroscopy predict neurodevelopmental outcome in very
      low birth weight preterm infants?
AB  - OBJECTIVE: To determine if metabolite ratios at near-term age predict outcome in
      very low birth weight preterm infants at 18 to 24 months adjusted age. STUDY
      DESIGN: Thirty-six infants (birth weight <or=1510 g, gestational age <or=32
      weeks) were scanned at a postmenstrual age (PMA) of 35 to 43 weeks from July 2001
      to September 2003. Multivoxel proton spectroscopic data were acquired and
      metabolite ratios were calculated in regions of the thalamus and basal ganglia.
      Bayley Scales of Infant Development were assessed between 18 and 24 months
      corrected age. RESULT: Metabolic ratios showed no significant correlation with
      developmental outcome. A correlation was seen between N-acetylaspartate
      (NAA)/choline (Ch) and PMA in thalamus and basal ganglia. CONCLUSION: Metabolite
      ratios from near-term proton magnetic resonance spectroscopy (MRS) were not
      predictive of Bayley scores at 18 to 24 months adjusted age. There was a positive
      correlation between NAA/Ch and PMA, which supports previous work by others for
      the importance of developmental changes in the MRS with age.

PMID- 18615092
TI  - Epigenetic regulation and nucleosome positioning in the human TATA-less IL-1
      alpha promoter.
AB  - Interleukin-1 alpha (IL-1 alpha) is secreted by a variety of cell types and is a
      major player in immune and inflammatory processes. Genes involved in
      immunological processes are known to be strictly regulated; however, how
      epigenetic mechanisms contribute to this regulation in not understood. To gain
      insight into the epigenetic regulation of the human TATA-less IL-1A gene, we show
      that active and silent chromatin modifications characterize the regulatory
      regions of IL-1 alpha in expressing and non-expressing cells, respectively, and
      that the DNA methylation in the proximal promoter is associated with the
      expression status of the cells. Interestingly, although nucleosome depletion in
      active promoters is found in yeast and fly genes, now it has been reported in
      human promoters. We here show on the level of single DNA molecules that in
      expressing cells, a nucleosome is absent in about half of the proximal IL-1 alpha
      promoters. This observation might reflect a more subtle regulation of nucleosome
      positioning in TATA-less genes or human genes in general.

PMID- 18615093
TI  - HLA-DRB1*15 allele influences the later course of relapsing remitting multiple
      sclerosis.
AB  - Most of the published works so far have aimed at finding genes associated with
      multiple sclerosis (MS) susceptibility. Very few studies have attempted to
      correlate disease features with DNA variants. In a well-characterized sample (651
      patients) representative of multiple sclerosis natural history, we engaged a
      comprehensive study of the role of human leukocyte antigen (HLA) in the course of
      the disease. We investigated the role of HLA-DRB1*15 allele in samples stratified
      according to severity evaluated by the Multiple Sclerosis Severity Score (MSSS),
      time to reach EDSS 6.0 and disease type. We found that HLA-DRB1*15 genotype does
      not influence MS severity even among patients presenting with a given type of the
      disease. However, we show for the first time that HLA-DRB1*15 allele modulates
      the course of MS for relapsing-remitting (RR) onset patients likely by
      precipitating the secondary progressive (SP) phase.

PMID- 18615094
TI  - A novel insertion variant of the human IL-23 receptor-alpha chain transcript.
AB  - Alternative splicing of mRNA is an important mechanism for organisms to enhance
      protein diversity from a limited number of genes. In this report, we described a
      novel exon insertion in the interleukin 23 (IL-23) receptor between exons 9 and
      10, denoted as exon 9a. This 162 base-pair insertion was the only insertion
      variant discovered in more than 20 IL23R deletion variants found in the mRNA of
      mitogen-stimulated peripheral blood mononuclear cells (PBMC). Sequence analysis
      revealed that a pair of GT/AG splice donor-acceptor site and several putative cis
      acting sequences were present; the insertion was identified throughout the genome
      and found to contain homology to the L1 retrotransposon protein. This report
      describes an insertion in the IL-23 receptor and due to consequent early
      termination within the intracellular region, causing a possible non-responsive
      receptor isoform.

PMID- 18615095
TI  - A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case
      control and a family study in Tunisia.
AB  - Asthma is a complex genetic disorder characterized by chronic airway
      inflammation. We hypothesized that genetic polymorphisms in chemokines and their
      receptors alter leukocyte mobilization and may thus influence the risk and
      severity of childhood asthma. Distributions of the chemokine CCL2-2578G, CCL2
      927C, CCR2-V64I, CX3CR1-V249I and CX3CR1-T280M receptor polymorphisms were
      examined in a case-control study of 121 children with asthma and 226 age-matched
      healthy controls and then replicated in a family study of 99 simplex families
      (297 individuals). The case-control study revealed that the CCL2-2578G allele was
      less frequent in children with than in those without asthma (P=0.0012). No
      association with asthma was found for the CCL2-927, CCR2 or CX3CR1 polymorphisms.
      The finding in the family study that the CCL2-2578G allele was transmitted less
      often by heterozygous parents to their children with asthma (P=0.0016) confirms
      the association of CCL2-2578G with asthma risk. Biochemical studies indicated
      that plasma CCL2 concentrations were higher in both patients (P=0.0214) and
      controls (P=0.001) carrying the G allele than in subjects with other
      polymorphisms. Both case-control and family-based studies suggest a protective
      effect of allele CCL2-2578G in Tunisian asthmatic children.

PMID- 18615096
TI  - Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde
      transport in neurons.
AB  - The transport of vesicles in neurons is a highly regulated process, with vesicles
      moving either anterogradely or retrogradely depending on the nature of the
      molecular motors, kinesins and dynein, respectively, which propel vesicles along
      microtubules (MTs). However, the mechanisms that determine the directionality of
      transport remain unclear. Huntingtin, the protein mutated in Huntington's
      disease, is a positive regulatory factor for vesicular transport. Huntingtin is
      phosphorylated at serine 421 by the kinase Akt but the role of this modification
      is unknown. Here, we demonstrate that phosphorylation of wild-type huntingtin at
      S421 is crucial to control the direction of vesicles in neurons. When
      phosphorylated, huntingtin recruits kinesin-1 to the dynactin complex on vesicles
      and MTs. Using brain-derived neurotrophic factor as a marker of vesicular
      transport, we demonstrate that huntingtin phosphorylation promotes anterograde
      transport. Conversely, when huntingtin is not phosphorylated, kinesin-1 detaches
      and vesicles are more likely to undergo retrograde transport. This also applies
      to other vesicles suggesting an essential role for huntingtin in the control of
      vesicular directionality in neurons.

PMID- 18615097
TI  - The Tat system proofreads FeS protein substrates and directly initiates the
      disposal of rejected molecules.
AB  - The twin-arginine translocation (Tat) system transports folded proteins across
      the bacterial plasma membrane, including FeS proteins that receive their
      cofactors in the cytoplasm. We have studied two Escherichia coli Tat substrates,
      NrfC and NapG, to examine how, or whether, the system exports only correctly
      folded and assembled FeS proteins. With NrfC, substitutions in even one of four
      predicted FeS centres completely block export, indicating an effective
      proofreading activity. The FeS mutants are rapidly degraded but only if they
      interact with the Tat translocon; they are stable in a tat deletion strain and
      equally stable in wild-type cells if the signal peptide twin-arginine motif is
      removed to block targeting. Basically similar results are obtained with NapG. The
      Tat apparatus thus proofreads these substrates and directly initiates the
      turnover of rejected molecules. Turnover of mutated FeS substrates is completely
      dependent on the TatA/E subunits that are believed to be involved in the late
      stages of translocation, and we propose that partial translocation triggers
      substrate turnover within an integrated quality control system for FeS proteins.

PMID- 18615099
TI  - Does psychosocial stress cause hypertension? A systematic review of observational
      studies.
AB  - Acute stress promotes transient elevation of blood pressure, but there is no
      consistent evidence that this effect results in hypertension. In this systematic
      review of cohort and case-control studies that investigated the association
      between psychosocial stress and hypertension, we conducted a complete search up
      to February 2007 in MEDLINE, EMBASE, PSYCINFO and LILACS, through a search
      strategy that included eight terms to describe the exposure, six related to the
      design of the studies and one term for outcome. The quality was assessed by the
      Newcastle-Ottawa Quality Assessment Scale. The selection was done in duplicate by
      two teams of independent reviewers. Among 82 studies selected in the second
      phase, only 14 (10 cohort studies and 4 case-control studies), totalling 52,049
      individuals, fulfilled the selection criteria. The average quality of the studies
      was 6.6+/-1.3 in a 9-point scale. Acute life events were associated with
      hypertension in one and were not associated in two studies. Five out of seven
      studies found a significant and positive association between measures of chronic
      stress and hypertension, with risk ratios ranging from 0.8 to 11.1. Three out of
      five studies reported high and significant risks of affective response to stress
      for hypertension, one a significant risk close to a unit and one reported absence
      of risk. Acute stress is probably not a risk factor for hypertension. Chronic
      stress and particularly the non-adaptive response to stress are more likely
      causes of sustained elevation of blood pressure. Studies with better quality are
      warranted.

PMID- 18615098
TI  - Nuclear import of CaMV P6 is required for infection and suppression of the RNA
      silencing factor DRB4.
AB  - Replication of Cauliflower mosaic virus (CaMV), a plant double-stranded DNA
      virus, requires the viral translational transactivator protein P6. Although P6 is
      known to form cytoplasmic inclusion bodies (viroplasms) so far considered
      essential for virus biology, a fraction of the protein is also present in the
      nucleus. Here, we report that monomeric P6 is imported into the nucleus through
      two importin-alpha-dependent nuclear localization signals, and show that this
      process is mandatory for CaMV infectivity and is independent of translational
      transactivation and viroplasm formation. One nuclear function of P6 is to
      suppress RNA silencing, a gene regulation mechanism with antiviral roles,
      commonly counteracted by dedicated viral suppressor proteins (viral silencing
      suppressors; VSRs). Transgenic P6 expression in Arabidopsis is genetically
      equivalent to inactivating the nuclear protein DRB4 that facilitates the activity
      of the major plant antiviral silencing factor DCL4. We further show that a
      fraction of P6 immunoprecipitates with DRB4 in CaMV-infected cells. This study
      identifies both genetic and physical interactions between a VSR to a host RNA
      silencing component, and highlights the importance of subcellular
      compartmentalization in VSR function.

PMID- 18615100
TI  - Initial combination therapy for rapid and effective control of moderate and
      severe hypertension.
AB  - Moderate (grade 2) and severe (grade 3) hypertension are important public health
      problems associated with high cardiovascular risk. Blood pressure (BP) control
      becomes more difficult to achieve as hypertension progresses. Therefore, early
      and effective treatment is essential to prevent hypertensive urgencies and
      emergencies and reduce cardiovascular risk. Currently, less than 50% of patients
      being treated for moderate or severe hypertension in the United States achieve
      their BP goal as recommended by treatment guidelines. This review examines the
      cardiovascular risk and physician inertia associated with moderate and severe
      hypertension, and concludes that increased use of initial combination therapy can
      overcome many of the barriers to effective BP control. Furthermore, initial
      combination therapy with a renin-angiotensin system (RAS) inhibitor and diuretic
      has the potential to rapidly and effectively reduce BP across a range of baseline
      BPs, with a comparable adverse event profile to monotherapy.

PMID- 18615102
TI  - High-throughput mutational screen of the tyrosine kinome in chronic
      myelomonocytic leukemia.

PMID- 18615101
TI  - The expression of 16 genes related to the cell of origin and immune response
      predicts survival in elderly patients with diffuse large B-cell lymphoma treated
      with CHOP and rituximab.
AB  - Gene expression profiles have been associated with clinical outcome in patients
      with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-containing
      chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma
      transcriptional profile of 30 patients treated with CHOP (cyclophosphamide,
      doxorubicin, vincristine, prednisone) and 23 patients treated with rituximab (R)
      CHOP in the Groupe d'Etude des Lymphomes de l'Adulte clinical centers. We used
      this data set to select transcripts showing an association with progression-free
      survival in all patients or showing a differential effect in the two treatment
      groups. We performed real-time quantitative reverse transcription-PCR in the 23 R
      CHOP samples of the screening set and an additional 44 R-CHOP samples set to
      evaluate the prognostic significance of these transcripts. In these 67 patients,
      the level of expression of 16 genes and the cell-of-origin classification were
      significantly associated with overall survival, independently of the
      International Prognostic Index. A multivariate model comprising four genes of the
      cell-of-origin signature (LMO2, MME, LPP and FOXP1) and two genes related to
      immune response, identified for their differential effects in R-CHOP patients
      (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of
      patients, suggesting that both features affect outcome in DLBCL patients
      receiving immunochemotherapy.

PMID- 18615103
TI  - Coding polymorphisms in CD33 and response to gemtuzumab ozogamicin in pediatric
      patients with AML: a pilot study.

PMID- 18615104
TI  - Kinetics of humoral response to ALK and its relationship with minimal residual
      disease in pediatric ALCL.

PMID- 18615105
TI  - Absolute quantitative detection of ABL tyrosine kinase domain point mutations in
      chronic myeloid leukemia using a novel nanofluidic platform and mutation-specific
      PCR.

PMID- 18615106
TI  - Combining SDF-1/CXCR4 antagonism and chemotherapy in relapsed acute myeloid
      leukemia.

PMID- 18615107
TI  - Highly sensitive and quantitative detection of BCR-ABL kinase domain mutations by
      ligation PCR.

PMID- 18615108
TI  - Dic(9;20)(p13;q11) in childhood acute lymphoblastic leukaemia is related to low
      cellular resistance to asparaginase, cytarabine and corticosteroids.

PMID- 18615109
TI  - Spontaneous and Fas-induced apoptosis of low-grade MDS erythroid precursors
      involves the endoplasmic reticulum.
AB  - Spontaneous apoptosis of bone marrow erythroid precursors accounts for the anemia
      that characterizes most low-grade myelodysplastic syndromes (MDS). We have shown
      that death of these precursors involved the Fas-dependent activation of caspase
      8. To explore the pathway leading from caspase-8 activation to apoptosis, we
      transduced MDS bone marrow CD34(+) cells with a lentivirus encoding wild-type
      (WT) or endoplasmic reticulum (ER)-targeted Bcl-2 protein before inducing their
      erythroid differentiation. Both WT-Bcl-2 and ER-targeted Bcl-2 prevented
      spontaneous and Fas-dependent apoptosis in MDS erythroid precursors. ER-targeted
      Bcl-2 inhibited mitochondrial membrane depolarization and cytochrome c release in
      MDS erythroid precursors undergoing apoptosis, indicating a role for the ER in
      the death pathway, upstream of the mitochondria. MDS erythroid precursors
      demonstrated elevated ER Ca(2+) stores and these stores remained unaffected by ER
      targeted Bcl-2. The ER-associated protein Bcl-2-associated protein (BAP) 31 was
      cleaved by caspase-8 in MDS erythroid precursors undergoing apoptosis. The
      protective effect of ER-targeted Bcl-2 toward spontaneous and Fas-induced
      apoptosis correlated with inhibition of BAP31 cleavage. A protective effect of
      erythropoietin against Fas-induced BAP31 cleavage and apoptosis was observed. We
      propose that apoptosis of MDS erythroid precursors involves the ER, downstream of
      Fas and upstream of the mitochondria, through the cleavage of the ER-associated
      BAP31 protein.

PMID- 18615110
TI  - Overexpression of IL-1alpha in skin differentially modulates the immune response
      to scarification with vaccinia virus.
AB  - Transepidermal inoculation of vaccinia virus (VV), or scarification, has been
      used effectively for the induction of specific and long-lasting immunity to
      smallpox and is superior to other routes of immunization. Scarification of
      individuals with atopic skin disease or immune deficiency, however, can lead to
      persistent viral replication and result in significant morbidity and mortality.
      These effects of scarification presumably reflect the unique immunological
      properties of skin and the immune cells resident in, or recruited to, the site of
      inoculation. To explore these phenomena, we utilized transgenic mice engineered
      to overexpress IL-1alpha, a critical mediator of cutaneous inflammation, in the
      epidermis. Following scarification with VV, both transgenic and wild-type mice
      develop local pox. At high doses of VV, IL-1alpha transgenic mice recruited
      immune cells to the inoculation site more rapidly and demonstrated enhanced T
      cell and humoral immune responses. At limiting doses, however, IL-1alpha
      transgenic mice could effectively control virus replication without formation of
      pox lesions or activation of a memory response. This study suggests that IL-1
      might be useful as an adjuvant to enhance antiviral immunity and promote safer
      vaccination strategies; however, understanding the balance of IL-1 effects on
      innate and adaptive immune functions will be critical to achieve optimal results.

PMID- 18615111
TI  - Overseas sun exposure, nevus counts, and premature skin aging in young English
      women: a population-based survey.
AB  - A large number of melanocytic nevi is the strongest known risk factor for
      melanoma in whites, but its relationship to sun exposure overseas among young
      white women living in temperate climates is unclear. A total of 754 white English
      women aged 18-46 years were recruited into a cross-sectional study in 1997-2000
      to investigate the effect of ultraviolet exposures on numbers of nevi and
      atypical nevi, and on skin aging as measured by microtopography. Having ever
      holidayed in hotter countries was associated with a greater age- and phenotype
      adjusted mean number of whole-body nevi (percent increase=74; 95% confidence
      interval: 24, 144; P=0.001), particularly for holidays taken at ages 18-29 years
      and for counts of the trunk and lower limbs. Having ever lived overseas was not
      associated with nevus counts, but was inversely associated with number of
      atypical nevi (P=0.02). Skin aging was not associated with residence or holidays
      abroad. The association of holidays overseas with an increased nevus count in
      young white women, which was stronger in the anatomical sites intermittently
      exposed to sunlight, supports the hypothesis that intermittent sun exposure is of
      relevance in the etiology of nevi and, hence, melanoma. The findings are of
      public health relevance given the growing popularity of foreign holidays.

PMID- 18615112
TI  - Recent trends in incidence of cutaneous melanoma among US Caucasian young adults.

PMID- 18615113
TI  - Semaphorin3A alleviates skin lesions and scratching behavior in NC/Nga mice, an
      atopic dermatitis model.
AB  - Topical steroids and antihistamines are commonly used for the treatment of atopic
      dermatitis (AD). However, in a substantial number of patients with AD, these
      treatments are not sufficiently effective. In AD patients, C-fibers in the
      epidermis increase and sprout, inducing hypersensitivity, which is considered to
      aggravate the disease. Semaphorin3A (Sema3A), an axon guidance molecule, is a
      potent inhibitor of neurite outgrowth of sensory neurons. To investigate the
      effect of Sema3A on AD, we administered recombinant Sema3A intracutaneously into
      the skin lesions of NC/Nga mice, an animal model of AD. Sema3A dose-dependently
      improved skin lesions and attenuated the scratching behavior in NC/Nga mice.
      Histological examinations revealed a decrease in: (a) epidermal thickness; (b)
      the density of invasive nerve fibers in the epidermis; (c) inflammatory
      infiltrates, including mast cells and CD4+ T cells; and (d) the production of IL
      4 in the Sema3A-treated lesions. Because the interruption of the itch-scratch
      cycle likely contributes to the improvement of the AD-like skin lesions, Sema3A
      is promising in the treatment of patients with refractory AD, as well as overall
      itching dermatosis.

PMID- 18615114
TI  - Patients with chronic mucocutaneous candidiasis exhibit reduced production of
      Th17-associated cytokines IL-17 and IL-22.
AB  - Chronic mucocutaneous candidiasis (CMC) constitutes a selective inability to
      clear infection with the yeast Candida, resulting in persistent debilitating
      inflammation of skin, nails, and mucous membranes. The underlying defect is
      unknown. Only recently, IL-17-producing T cells have been reported to be involved
      in clearing Candida infections. In order to characterize T cellular immune
      response to Candida, we analyzed T-cell cytokine secretion to Candida antigen and
      mitogenic stimuli in CMC patients, immunocompetent patients suffering from acute
      Candida infection, and healthy volunteers. Peripheral blood mononuclear cells
      (PBMCs) from CMC patients produced significantly lower amounts of IL-17 and IL-22
      mRNA and protein when stimulated with Candida albicans or mitogen in vitro
      compared with that in matched healthy individuals. Additionally, PBMCs from
      immunocompetent Candida-infected patients secreted more IL-17 and IL-22 than
      those of both CMC patients and healthy, non-infected controls. Flow cytometry
      revealed a decreased number of CCR6+ IL-17-producing T cells in CMC patients,
      whereas the amount of CCR6+/CCR4+ cells was not altered. Levels of
      differentiating cytokines for human Th17 cells, IL-1beta and IL-6, tended to be
      higher in CMC patients. The inability to clear C. albicans in CMC patients could
      be due to a defect in the immune response of IL-17-producing T cells.

PMID- 18615115
TI  - Complex interactions with several arms of the complement system dictate innate
      and humoral immunity to adenoviral vectors.
AB  - The complement system is known to play critical roles in pathogen identification,
      initiation of innate immune responses and facilitation of adaptive immune
      responses. Several studies have suggested that recombinant adenoviruses (rAds)
      interact with proteins of the complement system within minutes of administration.
      In this study, we assessed the roles of the alternative (Factor B), classical
      (C1q and C4) and common (C3) arms of the complement system in the innate and
      humoral response to systemic rAd administration using mice genetically deficient
      for each of these functions. Although most plasma cytokines and chemokines
      induced by Ads appeared to be elicited in a C3-dependent manner, we found that
      rAd-induced thrombocytopenia was dependent on Factor B and C3, implicating the
      alternative pathway as responsible for this response. Alteration of the
      complement-dependent transcriptome response after rAd-induced liver gene
      expression was also found to be Factor B- and C3-dependent. Ad interactions with
      the classical and alternative arms of the complement system can also be
      redundant, as many complement-dependent, Ad-induced innate immune responses
      appeared to be primarily C3-dependent. We also identified a C3 dependence of Ad
      mediated induction of the nuclear factor-kappaB (NF-kappaB) activation pathway.
      Finally, we confirmed that humoral immune responses to the vector capsid, and the
      transgene it encodes, are also complement-dependent.

PMID- 18615116
TI  - Augmentation of AAV-mediated cardiac gene transfer after systemic administration
      in adult rats.
AB  - Adeno-associated virus (AAV)-6 or -9-pseudotyped vectors are suitable for
      efficient cardiac gene transfer after intravenous injection in mice. However, a
      systemic application in larger animals or humans would require very high doses of
      viral particles. Therefore, the aim of our study was to test if ultrasound
      targeted microbubble destruction could augment cardiac transduction of AAV
      vectors after intravenous administration in rats. To analyze efficiency and
      specificity of gene transfer, microbubbles loaded with AAV-6 or -9 harboring a
      luciferase or enhanced green fluorescent protein (EGFP) reporter gene were
      infused into the jugular vein of adult Sprague-Dawley rats. During the infusion,
      high mechanical index ultrasound was administered to the heart. Control rats
      received the same amount of virus without microbubbles, but with ultrasound.
      After 4 weeks, organs were harvested and analyzed for reporter gene expression.
      In contrast to low cardiac expression after systemic transfer of the vector
      solution without microbubbles, ultrasound-targeted destruction of microbubbles
      significantly increased cardiac reporter activities between 6- and 20-fold.
      Analysis of spatial distribution of transgene expression using an AAV-9 vector
      encoding for EGFP revealed transmural expression predominantly in the left
      ventricular anterior wall. In conclusion, ultrasound targeted microbubble
      destruction augments cardiac transduction of AAV vectors in rats. This approach
      may be suitable for efficient, specific and noninvasive AAV-mediated gene
      transfer in larger animals or humans.

PMID- 18615117
TI  - Microbial contributions to climate change through carbon cycle feedbacks.
AB  - There is considerable interest in understanding the biological mechanisms that
      regulate carbon exchanges between the land and atmosphere, and how these
      exchanges respond to climate change. An understanding of soil microbial ecology
      is central to our ability to assess terrestrial carbon cycle-climate feedbacks,
      but the complexity of the soil microbial community and the many ways that it can
      be affected by climate and other global changes hampers our ability to draw firm
      conclusions on this topic. In this paper, we argue that to understand the
      potential negative and positive contributions of soil microbes to land-atmosphere
      carbon exchange and global warming requires explicit consideration of both direct
      and indirect impacts of climate change on microorganisms. Moreover, we argue that
      this requires consideration of complex interactions and feedbacks that occur
      between microbes, plants and their physical environment in the context of climate
      change, and the influence of other global changes which have the capacity to
      amplify climate-driven effects on soil microbes. Overall, we emphasize the urgent
      need for greater understanding of how soil microbial ecology contributes to land
      atmosphere carbon exchange in the context of climate change, and identify some
      challenges for the future. In particular, we highlight the need for a multifactor
      experimental approach to understand how soil microbes and their activities
      respond to climate change and consequences for carbon cycle feedbacks.

PMID- 18615119
TI  - Effect of HIV infection on the course of syphilis.
AB  - Syphilis has been a public health problem for centuries. Syphilis and HIV form a
      dangerous combination: syphilis significantly increases the risk of contracting
      HIV infection, and HIV can alter the natural course of syphilis. Despite a better
      understanding of the interaction between these two diseases, many controversies
      persist. The incidence of syphilis has increased among HIV-infected patients both
      in Europe and in the USA, and especially in the homosexual/bisexual transmission
      group. We discuss the interaction between HIV/AIDS and syphilis in a review of
      the most recent literature, focusing particularly on the diagnosis, treatment,
      and follow-up of HIV-infected patients with syphilis. Early diagnosis of syphilis
      in HIV-infected patients requires awareness among both patients and clinicians.
      Early treatment of syphilis is crucial as it reduces the risk of transmission.

PMID- 18615120
TI  - Minority report: hidden memory genomes in HIV-1 quasispecies and possible
      clinical implications.
AB  - The RNA viruses replicate as complex distributions of closely related genomes
      termed viral quasispecies. The behavior of the evolving quasispecies and its
      response to selective pressures such as antiviral treatment is influenced by the
      ensemble of mutants that compose the viral population. One such influence is the
      presence of minority subpopulations in the mutant spectra of viral quasispecies.
      Biologically relevant mutants have long been known to be present as minority
      components of replicating viral populations. However, experiments designed with
      specific mutants of the animal pathogen foot-and-mouth disease virus in cell
      culture explained the presence of a class of minority genomes termed memory
      genomes. They descend from those variants that were dominant at an earlier phase
      of quasispecies evolution, and arise as a consequence of quasispecies dynamics,
      when viral populations are subjected to discontinuous selective pressures. The
      presence of memory genomes has also been documented during intrahost evolution of
      HIV-1 in vivo. The analysis of sequential viral samples of different HIV-1
      infected patients showed that two distinct types of memory can operate in
      retroviruses: a replicative memory analogous to that observed in foot-and-mouth
      disease virus, as well as a reservoir memory derived from the integrative phase
      of the retroviral lifecycle. Despite being hidden as minority components of the
      HIV-1 viral population (ranging from about 0.1 to 20% of the total number of
      genomes in the quasispecies analyzed), memory genomes can drive the evolution of
      the virus during HIV-1 infections under antiviral therapy. The limited
      availability of current experimental data on minority HIV-1 subpopulations in
      vivo implies that further studies are required in order to define the cutoffs of
      clinically relevant minority genomes. Nevertheless, it is already evident that
      such low-abundance genomes remain undetectable by traditional genotyping methods
      such as consensus sequencing or conventional hybridization techniques. Several
      experimental systems are currently available for the detection and
      characterization of minority components of the mutant spectra of viral
      quasispecies including HIV, hepatitis C virus and hepatitis B virus. Some of
      these biotechnological approaches could, in the near future, be taken over and
      exploited in the clinical setting as useful biosensors with which to improve the
      management of HIV-infected patients.

PMID- 18615122
TI  - Restorative interventions for HIV facial lipoatrophy.
AB  - Facial lipoatrophy is a common and distressing manifestation of HIV
      lipodystrophy. The changes in facial appearance can reduce quality of life, self
      esteem and antiretroviral adherence. Apart from the modest benefits of thymidine
      based nucleoside analog cessation, there are no proven therapies for lipoatrophy.
      Management of established fat loss can be challenging as restoration of lost fat
      mass is extremely gradual. Plastic surgery and cosmetic procedures can restore
      lost facial volume. Both biodegradable and permanent filling agents have been
      investigated for HIV facial lipoatrophy. Biodegradable products offer a good
      safety profile, but maintenance of aesthetic benefits necessitates reinjection
      over time. Although permanent products offer longevity and lower treatment costs,
      adverse events should they occur can be serious and of long duration. Despite the
      substantial increase in options for soft-tissue augmentation in recent years,
      well-performed clinical studies in HIV-infected adults with facial lipoatrophy
      are scarce, and long-term clinical safety data are lacking. This review will
      summarize available efficacy and safety data of the biodegradable and permanent
      agents utilized for soft-tissue augmentation in this population. Difficulties
      associated with comparing treatment efficacy data, assessment of facial
      lipoatrophy presence and severity, and measurement of facial fat will be
      discussed. Available data indicate that in HIV-infected adults, most filling
      agents have short-term clinically safety, and can provide aesthetic improvement
      and improve well-being, social functioning and quality of life. However, well
      designed studies with objectively assessed endpoints are needed to elucidate
      optimal treatments for this distressing condition.

PMID- 18615121
TI  - Risk for immune-mediated liver reactions by nevirapine revisited.
AB  - Implementation of combination antiretroviral therapies has transformed the
      prognosis of HIV infection during the past decade. Because of its low-pill
      burden, convenient administration once or twice daily without food restrictions
      and, in the case of nevirapine, favorable metabolic profile and proven safety in
      pregnant women and newborns, nonnucleoside reverse transcriptase inhibitors have
      been shown to be often superior to protease inhibitors as third agents in
      combination with a backbone of two nucleoside reverse transcriptase inhibitors.
      Therefore, two nucleoside reverse transcriptase inhibitors plus one nonnucleoside
      reverse transcriptase inhibitor are currently the most popular used first-line
      therapies. Hepatotoxicity during the first weeks of therapy with nevirapine,
      particularly when initiated in women with CD4 counts > 250 cells/mm3, has
      prompted changes in guidelines and led to a modification in the product label.
      Recent data, however, suggest that virologically suppressed patients under any
      other antiretroviral drug combination may safely switch to nevirapine as a part
      of a simplification strategy, regardless of their current CD4 count. This subset
      of patients does not show an increased risk of hepatotoxicity or rash with
      elevated CD4 counts, as has been reported in drug-naive HIV persons. This
      information is important and may expand the number of candidates who could
      benefit from nevirapine use, since a substantial proportion of HIV patients show
      metabolic abnormalities (dyslipidemia, insulin resistance, liver steatosis) and
      are at increased cardiovascular risk. Fortunately, many of these conditions may
      ameliorate or improve using nevirapine.

PMID- 18615123
TI  - AIDS-related malignancies--a new approach.

PMID- 18615124
TI  - Understanding the changing prevalence of K65R.

PMID- 18615125
TI  - New resistance score for tipranavir.

PMID- 18615118
TI  - HIV-1 drug resistance mutations: an updated framework for the second decade of
      HAART.
AB  - More than 200 mutations are associated with antiretroviral resistance to drugs
      belonging to six licensed antiretroviral classes. More than 50 reverse
      transcriptase mutations are associated with nucleoside reverse transcriptase
      inhibitor resistance including M184V, thymidine analog mutations, mutations
      associated with non-thymidine analog containing regimens, multi-nucleoside
      resistance mutations, and several recently identified accessory mutations. More
      than 40 reverse transcriptase mutations are associated with nonnucleoside reverse
      transcriptase inhibitor resistance including major primary and secondary
      mutations, non-polymorphic minor mutations, and polymorphic accessory mutations.
      More than 60 mutations are associated with protease inhibitor resistance
      including major protease, accessory protease, and protease cleavage site
      mutations. More than 30 integrase mutations are associated with the licensed
      integrase inhibitor raltegravir and the investigational inhibitor elvitegravir.
      More than 15 gp41 mutations are associated with the fusion inhibitor enfuvirtide.
      CCR5 inhibitor resistance results from mutations that promote gp120 binding to an
      inhibitor-bound CCR5 receptor or CXCR4 tropism; however, the genotypic correlates
      of these processes are not yet well characterized.

PMID- 18615126
TI  - Peripheral neuropathy induced by paclitaxel: recent insights and future
      perspectives.
AB  - Paclitaxel is an antineoplastic agent derived from the bark of the western yew,
      Taxus brevifolia, with a broad spectrum of activity. Because paclitaxel promotes
      microtubule assembly, neurotoxicity is one of its side effects. Clinical use of
      paclitaxel has led to peripheral neuropathy and this has been demonstrated to be
      dependent upon the dose administered, the duration of the infusion, and the
      schedule of administration. Vehicles in the drug formulation, for example
      Cremophor in Taxol, have been investigated for their potential to induce
      peripheral neuropathy. A variety of neuroprotective agents have been tested in
      animal and clinical studies to prevent paclitaxel neurotoxicity. Recently, novel
      paclitaxel formulations have been developed to minimize toxicities. This review
      focuses on recent advances in the etiology of paclitaxel-mediated peripheral
      neurotoxicity, and discusses current and ongoing strategies for amelioration of
      this side effect.

PMID- 18615127
TI  - Neuronal cell death in Alzheimer's disease and a neuroprotective factor, humanin.
AB  - Brain atrophy caused by neuronal loss is a prominent pathological feature of
      Alzheimer's disease (AD). Amyloid beta (Abeta), the major component of senile
      plaques, is considered to play a central role in neuronal cell death. In addition
      to removal of the toxic Abeta, direct suppression of neuronal loss is an
      essential part of AD treatment; however, no such neuroprotective therapies have
      been developed. Excess amount of Abeta evokes multiple cytotoxic mechanisms,
      involving increase of the intracellular Ca(2+) level, oxidative stress, and
      receptor-mediated activation of cell-death cascades. Such diversity in cytotoxic
      mechanisms induced by Abeta clearly indicates a complex nature of the AD-related
      neuronal cell death. We have identified a 24-residue peptide, Humanin (HN), which
      suppresses in vitro neuronal cell death caused by all AD-related insults,
      including Abeta, so far tested. The anti-AD effect of HN has been further
      confirmed in vivo using mice with Abeta-induced amnesia. Altogether, such potent
      neuroprotective activity of HN against AD-relevant cytotoxicity both in vitro and
      in vivo suggests the potential clinical applications of HN in novel AD therapies
      aimed at controlling neuronal death.

PMID- 18615128
TI  - Serotonin as a modulator of glutamate- and GABA-mediated neurotransmission:
      implications in physiological functions and in pathology.
AB  - The neurotransmitter serotonin (5-HT), widely distributed in the central nervous
      system (CNS), is involved in a large variety of physiological functions. In
      several brain regions 5-HT is diffusely released by volume transmission and
      behaves as a neuromodulator rather than as a "classical" neurotransmitter. In
      some cases 5-HT is co-localized in the same nerve terminal with other
      neurotransmitters and reciprocal interactions take place. This review will focus
      on the modulatory action of 5-HT on the effects of glutamate and gamma-amino
      butyric acid (GABA), which are the principal neurotransmitters mediating
      respectively excitatory and inhibitory signals in the CNS. Examples of
      interaction at pre-and/or post-synaptic levels will be illustrated, as well as
      the receptors involved and their mechanisms of action. Finally, the physiological
      meaning of neuromodulatory effects of 5-HT will be briefly discussed with respect
      to pathologies deriving from malfunctioning of serotonin system.

PMID- 18615129
TI  - The role of beta-amyloid protein in synaptic function: implications for
      Alzheimer's disease therapy.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive and irreversible loss of memory and other cognitive functions.
      Substantial evidence based on genetic, neuropathological and biochemical data has
      established the central role of beta-amyloid protein (betaAP) in this pathology.
      Although the precise etiology of AD is not well understood yet, strong evidence
      for some of the molecular events that lead to progressive brain dysfunction and
      neurodegeneration in AD has been afforded by identification of biochemical
      pathways implicated in the generation of betaAP, development of transgenic models
      exhibiting progressive disease pathology and by data on the effects of betaAP at
      the neuronal network level. However, the mechanisms by which betaAP causes
      cognitive decline have not been determined, nor is it clear if the degree of
      dementia correlates in time with the degree of neuronal loss. Hence, it is of
      interest to understand the biochemical processes involved in the mechanisms of
      betaAP-induced neurotoxicity and the mechanisms involved in electrophysiological
      effects of this protein on different parameters of synaptic transmission and on
      neuronal firing properties. In this review we analyze recent evidence suggesting
      a complex role of betaAP in the molecular events that lead to progressive loss of
      function and eventually to neurodegeneration in AD as well as the therapeutic
      implications based on betaAP metabolism inhibition.

PMID- 18615130
TI  - Heterotrimeric g proteins: insights into the neurobiology of mood disorders.
AB  - Mood disorders such as major depression and bipolar disorder are common, severe,
      chronic and often life-threatening illnesses. Suicide is estimated to be the
      cause of death in up to approximately 10-15% of individuals with mood disorders.
      Alterations in the signal transduction through G protein-coupled receptor (GPCR)
      pathways have been reported in the etiopathology of mood disorders and the
      suicidal behavior. In this regard, the implication of certain GPCR subtypes such
      as alpha(2A)-adrenoceptor has been repeatedly described using different
      approaches. However, several discrepancies have been recently reported in density
      and functional status of the heterotrimeric G proteins both in major depression
      and bipolar disorder. A compilation of the most relevant research topics about
      the implication of heterotrimeric G proteins in the etiology of mood disorders
      (i.e., animal models of mood disorders, studies in peripheral tissue of
      depressive patients, and studies in postmortem human brain of suicide victims
      with mood disorders) will provide a broad perspective of this potential
      therapeutic target field. Proposed causes of the discrepancies reported at the
      level of G proteins in postmortem human brain of suicide victims will be
      discussed.

PMID- 18615131
TI  - On the origin of cortical dopamine: is it a co-transmitter in noradrenergic
      neurons?
AB  - Dopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate
      superior cognitive functions, and are involved in the aetiology of depressive and
      psychotic symptoms. Moreover, microdialysis studies in rats have shown how
      pharmacological treatments that induce modifications of extracellular NA in the
      medial PFC (mPFC), also produce parallel changes in extracellular DA.To explain
      the coupling of NA and DA changes, this article reviews the evidence supporting
      the hypothesis that extracellular DA in the cerebral cortex originates not only
      from dopaminergic terminals but also from noradrenergic ones, where it acts both
      as precursor for NA and as a co-transmitter.Accordingly, extracellular DA
      concentration in the occipital, parietal and cerebellar cortex was found to be
      much higher than expected in view of the scarce dopaminergic innervation in these
      areas.Systemic administration or intra-cortical perfusion of alpha(2)
      adrenoceptor agonists and antagonists, consistent with their action on
      noradrenergic neuronal activity, produced concomitant changes not only in
      extracellular NA but also in DA in the mPFC, occipital and parietal
      cortex.Chemical modulation of the locus coeruleus by locally applied carbachol,
      kainate, NMDA or clonidine modified both NA and DA in the mPFC.Electrical
      stimulation of the locus coeruleus led to an increased efflux of both NA and DA
      in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone
      was enhanced.Atypical antipsychotics, such as clozapine and olanzapine, or
      antidepressants, including mirtazapine and mianserine, have been found to
      increase both NA and DA throughout the cerebral cortex, likely through blockade
      of alpha(2)-adrenoceptors. On the other hand, drugs selectively acting on
      dopaminergic transmission produced modest changes in extracellular DA in mPFC,
      and had no effect on the occipital or parietal cortex.Acute administration of
      morphine did not increase DA levels in the PFC (where NA is diminished), in
      contrast with augmented dopaminergic neuronal activity; moreover, during morphine
      withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic
      activity, both increases being antagonised by clonidine but not quinpirole
      administration.Extensive 6-hydroxy dopamine lesion of the ventral tegmental area
      (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC
      in the nucleus accumbens, but only partially or not significantly in the mPFC and
      parietal cortex.The above evidence points to a common origin for NA and DA in the
      cerebral cortex and suggests the possible utility of noradrenergic system
      modulation as a target for drugs with potential clinical efficacy on cognitive
      functions.

PMID- 18615132
TI  - Physiology and pharmacology of the vanilloid receptor.
AB  - The identification and cloning of the vanilloid receptor 1 (TRPV1) represented a
      significant step for the understanding of the molecular mechanisms underlying the
      transduction of noxious chemical and thermal stimuli by peripheral nociceptors.
      TRPV1 is a non-selective cation channel gated by noxious heat, vanilloids and
      extracellular protons. TRPV1 channel activity is remarkably potentiated by pro
      inflammatory agents, a phenomenon that is thought to underlie the peripheral
      sensitisation of nociceptors that leads to thermal hyperalgesia. Cumulative
      evidence is building a strong case for the involvement of this receptor in the
      etiology of both peripheral and visceral inflammatory pain, such as inflammatory
      bowel disease, bladder inflammation and cancer pain. The validation of TRPV1
      receptor as a key therapeutic target for pain management has thrust intensive
      drug discovery programs aimed at developing orally active antagonists of the
      receptor protein. Nonetheless, the real challenge of these drug discovery
      platforms is to develop antagonists that preserve the physiological activity of
      TRPV1 receptors while correcting over-active channels. This is a condition to
      ensure normal pro-prioceptive and nociceptive responses that represent a safety
      mechanism to prevent tissue injury. Recent and exciting advances in the function,
      dysfunction and modulation of this receptor will be the focus of this review.

PMID- 18615133
TI  - Mitochondrial toxins in Basal Ganglia disorders: from animal models to
      therapeutic strategies.
AB  - Current knowledge of the pathogenesis of basal ganglia disorders, such as
      Huntington's disease (HD) and Parkinson's disease (PD) appoints a central role to
      a dysfunction in mitochondrial metabolism. The development of animal models,
      based upon the use of mitochondrial toxins has been successfully introduced to
      reproduce human disease, leading to important acquisitions. Most notably,
      experimental evidence supports the existence, within basal ganglia, of a peculiar
      regional vulnerability to distinct mitochondrial toxins. MPTP and rotenone, both
      selective inhibitors of mitochondrial complex I have been extensively used to
      mimic PD. Accordingly, in human PD, a specific dysfunction of complex I activity
      was found in vulnerable dopaminergic neurons of the substantia nigra. Conversely,
      in HD a selective impairment of mitochondrial succinate dehydrogenase, key enzyme
      in complex II activity was found in medium spiny neurons of the caudate-putamen.
      The relevance of such finding is further demonstrated by the evidence that toxins
      able to primarily target mitochondrial complex II, such as malonic acid and 3
      nitropropionic acid (3-NP), strikingly reproduce the main phenotypic and
      pathological features of HD.Despite the advances obtained from these experimental
      models, a deeper understanding of the molecular and cellular mechanisms
      underlying such neuronal vulnerability is lacking.The present review provides a
      brief survey of currently utilized animal models of mitochondrial intoxication,
      in attempt to address the cellular mechanisms triggered by energy metabolism
      failure and to identify potential therapeutic targets.

PMID- 18615134
TI  - Metabotropic glutamate receptors in the trafficking of ionotropic glutamate and
      GABA(A) receptors at central synapses.
AB  - The trafficking of ionotropic glutamate (AMPA, NMDA and kainate) and GABA(A)
      receptors in and out of, or laterally along, the postsynaptic membrane has
      recently emerged as an important mechanism in the regulation of synaptic
      function, both under physiological and pathological conditions, such as
      information processing, learning and memory formation, neuronal development, and
      neurodegenerative diseases. Non-ionotropic glutamate receptors, primarily group I
      metabotropic glutamate receptors (mGluRs), co-exist with the postsynaptic
      ionotropic glutamate and GABA(A) receptors. The ability of mGluRs to regulate
      postsynaptic phosphorylation and Ca(2+) concentration, as well as their
      interactions with postsynaptic scaffolding/signaling proteins, makes them well
      suited to influence the trafficking of ionotropic glutamate and GABA(A)
      receptors. Recent studies have provided insights into how mGluRs may impose such
      an influence at central synapses, and thus how they may affect synaptic signaling
      and the maintenance of long-term synaptic plasticity. In this review we will
      discuss some of the recent progress in this area: i) long-term synaptic
      plasticity and the involvement of mGluRs; ii) ionotropic glutamate receptor
      trafficking and long-term synaptic plasticity; iii) the involvement of
      postsynaptic group I mGluRs in regulating ionotropic glutamate receptor
      trafficking; iv) involvement of postsynaptic group I mGluRs in regulating GABA(A)
      receptor trafficking; v) and the trafficking of postsynaptic group I mGluRs
      themselves.

PMID- 18615135
TI  - Animal models for the development of new neuropharmacological therapeutics in the
      status epilepticus.
AB  - Status epilepticus (SE) is a major medical emergency associated with significant
      morbidity and mortality. SE is best defined as a continuous, generalized,
      convulsive seizure lasting > 5 min, or two or more seizures during which the
      patient does not return to baseline consciousness. The relative efficacy and
      safety of different drugs in the treatment of human SE should be determined in a
      prospective, randomized, blinded study. However, complementary animal models of
      SE are required to answer important questions concerning the treatment of SE
      because of the obvious difficulties of setting up such studies in clinical
      emergency conditions. This review offers an overview of the implementation and
      characteristics of some of the most prevalent animal models of SE currently in
      use. A description is also provide about how animal models of SE may facilitate
      the use of neurobiological techniques to successfully address critical questions
      in the drug treatment of SE. In particular, the experience with recently
      introduced drugs such as intravenous valproate will be addressed. Finally, the
      importance of some animal models and pharmacological approaches is explained and
      we discuss their impact in the development of therapeutic strategies to improve
      pharmacological treatment for SE is discussed.

PMID- 18615136
TI  - Emotion, decision-making and substance dependence: a somatic-marker model of
      addiction.
AB  - Similar to patients with orbitofrontal cortex lesions, substance dependent
      individuals (SDI) show signs of impairments in decision-making, characterised by
      a tendency to choose the immediate reward at the expense of severe negative
      future consequences. The somatic-marker hypothesis proposes that decision-making
      depends in many important ways on neural substrates that regulate homeostasis,
      emotion and feeling. According to this model, there should be a link between
      abnormalities in experiencing emotions in SDI, and their severe impairments in
      decision-making in real-life. Growing evidence from neuroscientific studies
      suggests that core aspects of substance addiction may be explained in terms of
      abnormal emotional guidance of decision-making. Behavioural studies have revealed
      emotional processing and decision-making deficits in SDI. Combined
      neuropsychological and physiological assessment has demonstrated that the poorer
      decision-making of SDI is associated with altered reactions to reward and
      punishing events. Imaging studies have shown that impaired decision-making in
      addiction is associated with abnormal functioning of a distributed neural network
      critical for the processing of emotional information, including the ventromedial
      cortex, the amygdala, the striatum, the anterior cingulate cortex, and the
      insular/somato-sensory cortices, as well as non-specific neurotransmitter systems
      that modulate activities of neural processes involved in decision-making. The aim
      of this paper is to review this growing evidence, and to examine the extent of
      which these studies support a somatic-marker model of addiction.

PMID- 18615137
TI  - The action of prostaglandins on ion channels.
AB  - Prostaglandins, in particular PGE(2) and prostacyclin PGI(2) have diverse
      biological effects. Most importantly, they are involved in inflammation and pain.
      Prostaglandins in nano- and micromolar concentrations sensitize nerve cells, i.e.
      make them more sensitive to electrical or chemical stimuli. Sensitization arises
      from the effect of prostaglandins on ion channels and occurs both at the
      peripheral terminal of nociceptors at the site of tissue injury (peripheral
      sensitization) and at the synapses in the spinal cord (central sensitization).
      The first step is the binding of prostaglandins to receptors in the cell
      membrane, mainly EP and IP receptors. The receptors couple via G proteins to
      enzymes such as adenylate cyclase and phospholipase C (PLC). Activation of
      adenylate cyclase leads to increase of cAMP and subsequent activation of protein
      kinase A (PKA) or PKA-independent effects of cAMP, e.g. mediated by Epac
      (=exchange protein activated by cAMP). Activation of PLC causes increase of
      inositol phosphates and increase of cytosolic calcium. This article summarizes
      the effects of PGE(2), PGE(1), PGI2 and its stable analogues on non-selective
      cation channels and sodium, potassium, calcium and chloride channels. It
      describes the mechanism responsible for the facilitatory or inhibitory
      prostaglandin effects on ion channels. Understanding these mechanisms is
      essential for the development of useful new analgesics.

PMID- 18615140
TI  - Painful peripheral neuropathies.
AB  - Peripheral neuropathies are a heterogeneous group of diseases affecting
      peripheral nerves. The causes are multiple: hereditary, metabolic, infectious,
      inflammatory, toxic, traumatic. The temporal profile includes acute, subacute and
      chronic conditions. The majority of peripheral neuropathies cause mainly muscle
      weakness and sensory loss, positive sensory symptoms and sometimes pain. When
      pain is present, however, it is usually extremely intense and among the most
      disabling symptoms for the patients. In addition, the neurological origin of the
      pain is often missed and patients receive inadequate or delayed specific
      treatment. Independently of the disease causing the peripheral nerve injury, pain
      originating from axonal pathology or ganglionopathy privileges neuropathies
      affecting smaller fibres, a clinical observation that points towards abnormal
      activity within nociceptive afferents as a main generator of pain. Natural
      activation of blood vessels or perineurial nociceptive network by pathology also
      causes intense pain. Pain of this kind, i.e. nerve trunk pain, is among the
      heralding symptoms of inflammatory or ischemic mononeuropathy and for its
      intensity represents itself a medical emergency. Neuropathic pain quality
      rekindles the psychophysical experience of peripheral nerves intraneural
      microstimulation i.e. a combination of large and small fibres sensation
      temporally distorted compared to physiological perception evoked by natural
      stimuli. Pins and needles, burning, cramping mixed with numbness, and tingling
      are the wording most used by patients. Nociceptive pain instead is most often
      described as aching, deep and dull. Good command of peripheral nerve anatomy and
      pathophysiology allows timely recognition of the different pain components and
      targeted treatment, selected according to intensity, type and temporal profile of
      the pain.

PMID- 18615138
TI  - Cerebral arachidonate cascade in dementia: Alzheimer's disease and vascular
      dementia.
AB  - Phospholipase A(2) (PLA(2)), cyclooxygenase (COX) and prostaglandin (PG) synthase
      are enzymes involved in arachidonate cascade. PLA(2) liberates arachidonic acid
      (AA) from cell membrane lipids. COX oxidizes AA to PGG(2) followed by an
      endoperoxidase reaction that converts PGG(2) into PGH(2). PGs are generated from
      astrocytes, microglial cells and neurons in the central nervous system, and are
      altered in the brain of demented patients. Dementia is principally diagnosed into
      Alzheimer's disease (AD) and vascular dementia (VaD). In older patients, the
      brain lesions associated with each pathological process often occur together.
      Regional brain microvascular abnormalities appear before cognitive decline and
      neurodegeneration. The coexistence of AD and VaD pathology is often termed mixed
      dementia. AD and VaD brain lesions interact in important ways to decline
      cognition, suggesting common pathways of the two neurological diseases.
      Arachidonate cascade is one of the converged intracellular signal transductions
      between AD and VaD. PLA(2) from mammalian sources are classified as secreted
      (sPLA(2)), Ca(2+)-dependent, cytosolic (cPLA(2)) and Ca(2+)-independent cytosolic
      PLA(2) (iPLA(2)). PLA(2) activity can be regulated by calcium, by
      phosphorylation, and by agonists binding to G-protein-coupled receptors. cPLA(2)
      is upregulalted in AD, but iPLA(2) is downregulated. On the other hand, sPLA(2)
      is increased in animal models for VaD. COX-2 is induced and PGD(2) are elevated
      in both AD and VaD. This review presents evidences for central roles of PLA(2)s,
      COXs and PGs in the dementia.

PMID- 18615139
TI  - Modulation of midbrain dopamine neurotransmission by serotonin, a versatile
      interaction between neurotransmitters and significance for antipsychotic drug
      action.
AB  - Schizophrenia has been associated with a dysfunction of brain dopamine (DA).
      This, so called, DA hypothesis has been refined as new insights into the
      pathophysiology of schizophrenia have emerged. Currently, dysfunction of
      prefrontocortical glutamatergic and GABAergic projections and dysfunction of
      serotonin (5-HT) systems are also thought to play a role in the pathophysiology
      of schizophrenia. Refinements of the DA hypothesis have lead to the emergence of
      new pharmacological targets for antipsychotic drug development. It was shown that
      effective antipsychotic drugs with a low liability for inducing extra-pyramidal
      side-effects have affinities for a range of neurotransmitter receptors in
      addition to DA receptors, suggesting that a combination of neurotransmitter
      receptor affinities may be favorable for treatment outcome.This review focuses on
      the interaction between DA and 5-HT, as most antipsychotics display affinity for
      5-HT receptors. We will discuss DA/5-HT interactions at the level of receptors
      and G protein-coupled potassium channels and consequences for induction of
      depolarization blockade with specific attention to DA neurons in the ventral
      tegmental area (VTA) and the substantia nigra zona compacta (SN), neurons
      implicated in treatment efficacy and the side-effects of schizophrenia,
      respectively. Moreover, it has been reported that electrophysiological
      interactions between DA and 5-HT show subtle, but important, differences between
      the SN and the VTA which could explain (in part) the effectiveness and lower
      propensity to induce side-effects of the newer atypical antipsychotic drugs. In
      that respect the functional implications of DA/5-HT interactions for
      schizophrenia will be discussed.

PMID- 18615142
TI  - L-acetylcarnitine: a proposed therapeutic agent for painful peripheral
      neuropathies.
AB  - During the past two decades, many pharmacological strategies have been
      investigated for the management of painful neuropathies. However, neuropathic
      pain still remains a clinical challenge. A combination of therapies is often
      required, but unfortunately in most cases adequate pain relief is not achieved.
      Recently, attention has been focused on the physiological and pharmacological
      effects of L-acetylcarnitine in neurological disorders. There are a number of
      reports indicating that L-acetylcarnitine can be considered as a therapeutic
      agent in neuropathic disorders including painful peripheral neuropathies. In this
      review article, we will examine the antinociceptive and the neuroprotective
      effects of Lacetylcarnitine as tested in clinical studies and in animal models of
      nerve injury.

PMID- 18615141
TI  - The emerging role of TRP channels in mechanisms of temperature and pain
      sensation.
AB  - Pain is universal and vital to survival. It is an essential component of our
      sense of touch; together, touch and pain have evolved to enable our awareness of
      the intricacies of our environment and to warn us of danger and possible injury.
      There is a clear link between temperature sensation and pain-painful temperature
      sensations occur acutely and are a hallmark of inflammatory and chronic pain
      disorders of the nervous system. Mounting evidence suggests a subset of Transient
      Receptor Potential (TRP) ion channels activated by temperature (thermoTRPs) are
      important molecular players in acute, inflammatory and chronic pain states.
      Varying degrees of heat activate four of these channels (TRPV1-4), while cooling
      temperatures ranging from pleasant to painful activate two distantly related
      thermoTRP channels (TRPM8 and TRPA1). ThermoTRP channels are also chemosensitive,
      being activated and or modulated by plant-derived small molecules and endogenous
      inflammatory mediators. All thermoTRPs are expressed in tissues essential to
      cutaneous thermal and pain sensation. This review examines the contribution of
      thermoTRP channels to our understanding of temperature and pain transduction at
      the molecular level.

PMID- 18615143
TI  - Modulators of pain: Bv8 and prokineticins.
AB  - Bv8 is a small protein secreted by frog skin. Mammalian homologues of Bv8, the
      prokineticins PK1 and PK2, and their G-protein coupled receptors PKR1 and PKR2
      have been identified and linked to several biological effects. Bv8 elicits a dose
      dependent reduction in nociceptive threshold to thermal and mechanical stimuli
      applied to the skin of tail and paw of rats and mice and increases the
      sensitivity to nociceptive mediators as capsaicin and prostaglandins. The
      receptors for Bv8/PKs are present in a fraction of peptidergic population of C
      fibre neurons, and in a fraction of A myelinated-fibre neurons. In mouse and rat
      dorsal root ganglia, PKR-expressing neurons also express TRPV1 and the activation
      of PKRs sensitises TPRV1 to the action of capsaicin. Mice lacking PKR1 gene
      exhibit impaired Bv8-induced hyperalgesia, develop deficient responses to noxious
      heat, capsaicin and protons and show reduced thermal and mechanical
      hypersensitivity to paw inflammation, indicating a requirement for PKR1
      signalling associated with activation and sensitisation of primary afferent
      fibres. PKs are highly expressed by neutrophils and other inflammatory cells and
      must be considered as new pronociceptive mediators in inflammatory tissues. Bv8
      like hyperalgesic activity was demonstrated in extracts of rat inflammatory
      granulocytes. Bv8 stimulate macrophage and T lymphocyte to differentiate between
      an inflammatory and Th1 profile indicating that Bv8/PK proteins play a role in
      immuno-inflammatory responses. Blockade of PKRs may represent a novel therapeutic
      strategy in acute and inflammatory pain conditions.

PMID- 18615144
TI  - Role of the cannabinoid system in pain control and therapeutic implications for
      the management of acute and chronic pain episodes.
AB  - Cannabis extracts and synthetic cannabinoids are still widely considered illegal
      substances. Preclinical and clinical studies have suggested that they may result
      useful to treat diverse diseases, including those related with acute or chronic
      pain. The discovery of cannabinoid receptors, their endogenous ligands, and the
      machinery for the synthesis, transport, and degradation of these retrograde
      messengers, has equipped us with neurochemical tools for novel drug design.
      Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit
      release of pro-inflammatory molecules, and display synergistic effects with other
      systems that influence analgesia, especially the endogenous opioid system.
      Cannabinoid receptor agonists have shown therapeutic value against inflammatory
      and neuropathic pains, conditions that are often refractory to therapy. Although
      the psychoactive effects of these substances have limited clinical progress to
      study cannabinoid actions in pain mechanisms, preclinical research is progressing
      rapidly. For example, CB(1)mediated suppression of mast cell activation
      responses, CB(2)-mediated indirect stimulation of opioid receptors located in
      primary afferent pathways, and the discovery of inhibitors for either the
      transporters or the enzymes degrading endocannabinoids, are recent findings that
      suggest new therapeutic approaches to avoid central nervous system side effects.
      In this review, we will examine promising indications of cannabinoid receptor
      agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa
      extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have
      granted approval in Canada for the relief of neuropathic pain in multiple
      sclerosis. Further double-blind placebo-controlled clinical trials are needed to
      evaluate the potential therapeutic effectiveness of various cannabinoid agonists
      based medications for controlling different types of pain.

PMID- 18615145
TI  - PDZ domains at excitatory synapses: potential molecular targets for persistent
      pain treatment.
AB  - Persistent pain, a common clinical condition, could be caused by inflammation,
      tissue injury secondary to trauma or surgery, and nerve injuries. It is often
      inadequately controlled by current treatments, such as opioids and nonsteroidal
      anti-inflammatory drugs. The PDZ (Postsynaptic density 95, Discs large, and
      Zonula occludens-1) domains are ubiquitous protein interaction modules often
      found among multi-protein signaling complexes at neuronal synapses. Recent
      preclinical research shows that targeted disruption of PDZ domain-mediated
      protein interaction among N-methyl-Daspartate (NMDA) receptor signaling complexes
      significantly attenuates the development and maintenance of persistent pain
      without affecting nociceptive responsiveness to acute pain. PDZ domains at
      excitatory synapses may be new molecular targets for prevention and treatment of
      persistent pain. Here, we illustrate expression and distribution of the PDZ
      domain-containing proteins associated with NMDA receptors in the pain-related
      regions of the central nervous system, review the evidence for their roles in
      persistent pain states, and discuss potential mechanisms by which these PDZ
      domain-containing proteins are involved in persistent pain.

PMID- 18615147
TI  - Editorial.

PMID- 18615146
TI  - Inflammatory pain: the cellular basis of heat hyperalgesia.
AB  - Injury or inflammation release a range of inflammatory mediators that increase
      the sensitivity of sensory neurons to noxious thermal or mechanical stimuli. The
      heat- and capsaicin-gated channel TRPV1, which is an important detector of
      multiple noxious stimuli, plays a critical role in the development of thermal
      hyperalgesia induced by a wide range of inflammatory mediators. We review here
      recent findings on the molecular mechanisms of sensitisation of TRPV1 by
      inflammatory mediators, including bradykinin, ATP, NGF and prostaglandins. We
      describe the signalling pathways believed to be involved in the potentiation of
      TRPV1, and our current understanding of how inflammatory mediators couple to
      these pathways.

PMID- 18615148
TI  - Metabotropic glutamate and cannabinoid receptor crosstalk in periaqueductal grey
      pain processing.
AB  - Metabotropic glutamate (mGlu) and cannabinoid receptors are G-protein coupled
      receptors which have shown synaptic co-operation through small lipid messengers
      in the central nervous system (CNS). A functional interaction between these two
      receptor families could have a relevant potential in the treatment of CNS
      disorders, including chronic pain. Indeed, both mGlu and cannabinoid receptors
      play a crucial role in the neurobiology of pain and their simultaneous
      manipulation could lead to novel strategies in pain management. In particular, as
      both mGlu and cannabinoid receptors have been found in the periaqueductal gray
      (PAG), a crucial station in the pain modulatory system, these receptors could be
      a substrate for producing analgesia at this level. In this review we aim to
      briefly illustrate the role of mGlu and can-nabinoid receptors in controlling
      nociceptive processes, some points of convergence, and their functional
      interaction in pain processing. Further insights into this functional linkage
      between the mGlu and cannabinoid receptors could pave the way to a new strategy
      for pain relief, such as a drug cocktail acting on cannabinoid/metabotropic
      glutamate receptors.

PMID- 18615149
TI  - Sulfur mustard research--strategies for the development of improved medical
      therapy.
AB  - OBJECTIVE: Sulfur mustard (SM) is a bifunctional alkylating substance being used
      as chemical warfare agent (vesicant). It is still regarded as a significant
      threat in chemical warfare and terrorism. Exposure to SM produces cutaneous
      blisters, respiratory and gastrointestinal tract injury, eye lesions, and bone
      marrow depression. Victims of World War I as well as those of the Iran-Iraq war
      have suffered from devastating chronic health impairment. Even decades after
      exposure, severe long-term effects like chronic obstructive lung disease, lung
      fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal
      pigmentation of the skin, and different forms of cancer have been diagnosed.
      METHODS: This review briefly summarizes the scientific literature and own results
      concerning detection, organ toxicity of SM, its proposed toxicodynamic actions,
      and strategies for the development of improved medical therapy. RESULTS: Despite
      extensive research efforts during the last century, efficient antidotes against
      SM have not yet been generated because its mechanism of action is not fully
      understood. However, deeper insights into these mechanisms gained in the last
      decade and promising developments of new drugs now offer new chances to minimize
      SM-induced organ damage and late effects. CONCLUSION: Polymerase inhibitors, anti
      inflammatory drugs, antioxidants, matrix metalloproteinase inhibitors, and
      probably regulators of DNA damage repair are identified as promising approaches
      to improve treatment.

PMID- 18615150
TI  - Modelling anxiety in humans for drug development.
AB  - Animal behavioural profiles are commonly employed to investigate new therapeutic
      agents to treat anxiety disorders as well as to investigate the mechanism of
      action of anxiolytic drugs. However, many clinically important symptoms of
      anxiety can not be modelled directly in animals. Human models of anxiety should
      bridge between animal models and anxiety disorders. Experimental anxiety states
      in humans can be induced by either pharmacological means such as CO(2) inhalation
      or psychological means such as aversive conditioning of skin conductance
      responses to tones. Investigation of these models may contribute to a better
      understanding of anxiety disorders, both from a biological and behavioural point
      of view. In a comprehensive review existing models of human experimental anxiety
      states are summarized and validity is discussed.

PMID- 18615151
TI  - Brain slices as models for neurodegenerative disease and screening platforms to
      identify novel therapeutics.
AB  - Recent improvements in brain slice technology have made this biological
      preparation increasingly useful for examining pathophysiology of brain diseases
      in a tissue context. Brain slices maintain many aspects of in vivo biology,
      including functional local synaptic circuitry with preserved brain architecture,
      while allowing good experimental access and precise control of the extracellular
      environment, making them ideal platforms for dissection of molecular pathways
      underlying neuronal dysfunction. Importantly, these ex vivo systems permit direct
      treatment with pharmacological agents modulating these responses and thus provide
      surrogate therapeutic screening systems without recourse to whole animal studies.
      Virus or particle mediated transgenic expression can also be accomplished
      relatively easily to study the function of novel genes in a normal or injured
      brain tissue context.In this review we will discuss acute brain injury models in
      organotypic hippocampal and co-culture systems and the effects of pharmacological
      modulation on neurodegeneration. The review will also cover the evidence of
      developmental plasticity in these ex vivo models, demonstrating emergence of
      injury-stimulated neuronal progenitor cells, and neurite sprouting and axonal
      regeneration following pathway lesioning. Neuro-and axo-genesis are emerging as
      significant factors contributing to brain repair following many acute and chronic
      neurodegenerative disorders. Therefore brain slice models may provide a critical
      contextual experimental system to explore regenerative mechanisms in vitro.

PMID- 18615152
TI  - Agonism of Peroxisome Proliferator Receptor-Gamma may have Therapeutic Potential
      for Neuroinflammation and Parkinson's Disease.
AB  - Evidence suggests inflammation, mitochondria dysfunction, and oxidative stress
      play major roles in Parkinson's disease (PD), where the primary pathology is the
      significant loss of dopaminergic neurons in the substantia nigra (SN). Current
      methods used to treat PD focus mainly on replacing dopamine in the nigrostriatal
      system. However, with time these methods fail and worsen the symptoms of the
      disease. This implies there is more to the treatment of PD than just restoring
      dopamine or the dopaminergic neurons, and that a broader spectrum of factors must
      be changed in order to restore environmental homeostasis. Pharmacological agents
      that can protect against progressive neuronal degeneration, increase the level of
      dopamine in the nigrostriatal system, or restore the dopaminergic system offer
      various avenues for the treatment of PD. Drugs that reduce inflammation, restore
      mitochondrial function, or scavenge free radicals have also been shown to offer
      neuroprotection in various animal models of PD. The activation of peroxisome
      proliferator receptor- gamma (PPAR-gamma ) has been associated with altering
      insulin sensitivity, increasing dopamine, inhibiting inflammation, altering
      mitochondrial bioenergetics, and reducing oxidative stress - a variety of factors
      that are altered in PD. Therefore, PPAR-gamma activation may offer a new
      clinically relevant treatment approach to neuroinflammation and PD related
      neurodegeneration. This review will summarize the current understanding of the
      role of PPAR-gamma agonists in neuroinflammation and discuss their potential for
      the treatment of PD.

PMID- 18615154
TI  - Synaptic transmission at functionally identified synapses in the enteric nervous
      system: roles for both ionotropic and metabotropic receptors.
AB  - Digestion and absorption of nutrients and the secretion and reabsorption of fluid
      in the gastrointestinal tract are regulated by neurons of the enteric nervous
      system (ENS), the extensive peripheral nerve network contained within the
      intestinal wall. The ENS is an important physiological model for the study of
      neural networks since it is both complex and accessible. At least 20 different
      neurochemically and functionally distinct classes of enteric neurons have been
      identified in the guinea pig ileum. These neurons express a wide range of
      ionotropic and metabotropic receptors. Synaptic potentials mediated by ionotropic
      receptors such as the nicotinic acetylcholine receptor, P2X purinoceptors and 5
      HT(3) receptors are seen in many enteric neurons. However, prominent synaptic
      potentials mediated by metabotropic receptors, like the P2Y(1) receptor and the
      NK(1) receptor, are also seen in these neurons. Studies of synaptic transmission
      between the different neuron classes within the enteric neural pathways have
      shown that both ionotropic and metabotropic synaptic potentials play major roles
      at distinct synapses within simple reflex pathways. However, there are still
      functional synapses at which no known transmitter or receptor has been
      identified. This review describes the identified roles for both ionotropic and
      metabotropic neurotransmission at functionally defined synapses within the guinea
      pig ileum ENS. It is concluded that metabotropic synaptic potentials act as
      primary transmitters at some synapses. It is suggested identification of the
      interactions between different synaptic potentials in the production of complex
      behaviours will require the use of well validated computer models of the enteric
      neural circuitry.

PMID- 18615155
TI  - Plasminogen activator inhibitor-1 4G/5G gene polymorphism and primary open-angle
      glaucoma.
AB  - PURPOSE: Alterations of the plasmin system have been suggested to participate in
      the multifactorial pathogenesis of primary open-angle glaucoma (POAG). The main
      physiological inhibitor of the plasmin system is plasminogen activator inhibitor
      1 (PAI-1), which leads to decreased degradation of extracellular material.
      Interestingly, elevated PAI-1 levels in the aqueous humor of patients with POAG
      have been reported. A common polymorphism within the promoter region (PAI-1
      4G/5G) has previously been shown to reduce the gene transcription rate of PAI-1.
      The purpose of the present study was to investigate a hypothesized association
      between PAI-1 4G/5G and the presence of POAG in a Caucasian population. METHODS:
      The present case-control study comprised 212 unrelated patients with POAG and 212
      healthy control subjects, matched for age and sex. Genotyping of PAI-1 4G/5G
      polymorphisms was done using polymerase chain reaction. RESULTS: Allelic
      frequencies and genotype distributions of PAI-1 4G/5G did not significantly
      differ between patients with POAG and control subjects (PAI-1 4G/5G: 29.7% versus
      29.7%). Presence of the PAI-1 4G-allele was associated with a nonsignificant odds
      ratio of 0.98 (95% confidence interval: 0.74-1.30) for POAG. CONCLUSIONS: Our
      data suggest that PAI-1 4G/5G itself is unlikely to be a major risk factor among
      Caucasian patients with POAG.

PMID- 18615153
TI  - GABA and neuroactive steroid interactions in glia: new roles for old players?
AB  - In recent years it has becoming clear that glial cells of the central and
      peripheral nervous system play a crucial role from the earliest stages of
      development throughout adult life. Glial cells are important for neuronal
      plasticity, axonal conduction and synaptic transmission. In this respect, glial
      cells are able to produce, uptake and metabolize many factors that are essential
      for neuronal physiology, including classic neurotransmitters and neuroactive
      steroids. In particular, neuroactive steroids, which are mainly synthesized by
      glial cells, are able to modulate some neurotransmitter receptors affecting both
      glia and neurons. Among the signaling systems that are specialized for neuron
      glial communication, we can include neurotransmitter GABA.The main focus of this
      review is to illustrate the cross-talk between neurons and glial cells in terms
      of GABA neurotransmission and actions of neuroactive steroids. To this purpose,
      we will review the presence of the different GABA receptors in the glial cells of
      the central and peripheral nervous system. Then, we will discuss their modulation
      by some neuroactive steroids.

PMID- 18615156
TI  - Genome-wide association scan identifies candidate polymorphisms associated with
      differential response to anti-TNF treatment in rheumatoid arthritis.
AB  - The prediction of response (or non-response) to anti-TNF treatment for rheumatoid
      arthritis (RA) is a pressing clinical problem. We conducted a genome-wide
      association study using the Illumina HapMap300 SNP chip on 89 RA patients
      prospectively followed after beginning anti-TNF therapy as part of Autoimmune
      Biomarkers Collaborative Network (ABCoN [Autoimmune Bio-markers Collaborative
      Network]) patient cohort. Response to therapy was determined by the change in
      Disease Activity Score (DAS28) observed after 14 wks. We used a two-part analysis
      that treated the change in DAS28 as a continuous trait and then incorporated it
      into a dichotomous trait of "good responder" and "nonresponder" by European
      League Against Rheumatism (EULAR) criteria. We corrected for multiple tests by
      permutation, and adjusted for potential population stratification using
      EIGENSTRAT. Multiple single nucleotide polymorphism (SNP) markers showed
      significant associations near or within loci including: the v-maf
      musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene on chromosome 20;
      the type I interferon gene IFNk on chromosome 9; and in a locus on chromosome 7
      that includes the paraoxonase I (PON1) gene. An SNP in the IL10 promoter
      (rs1800896) that was previously reported as associated with anti-TNF response was
      weakly associated with response in this cohort. Replications of these results in
      independent and larger data sets clearly are required. We provide a reference
      list of candidate SNPs (P < 0.01) that can be investigated in future
      pharmacogenomic studies.

PMID- 18615158
TI  - No fun being picked on.

PMID- 18615159
TI  - Keeping cancer in perspective.

PMID- 18615157
TI  - Burn injury-induced alterations in wound inflammation and healing are associated
      with suppressed hypoxia inducible factor-1alpha expression.
AB  - A major complication associated with burn injury is delayed wound healing. While
      healing of the burn injury site is essential, healing of distal injury sites
      caused by surgical interventions and other processes also is important. The
      impact of burn injury on healing of these distal wound sites is not understood
      clearly. To study this, mice were subjected to major burn injury or a sham
      procedure. Immediately following, excisional wounds were made on the dorsal
      surface caudal to the burn site and wound closure was monitored over a 7-d period
      by planimetry. In a second series of experiments, plasma and excisional wounds
      were collected for in vitro analysis of cyto- and chemokine levels, L-arginine
      metabolism, and hypoxia-inducible factor (HIF)-1alpha expression. At 1-7 d post
      injury, a significant inflammatory response was evident in both groups, but the
      healing process was delayed in the burn-injured mice. At 3 d post-injury, wound
      levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
      keratinocyte-derived chemokine were suppressed in the burn group. This difference
      in the wound inflammatory response was independent of changes in L-arginine
      metabolism (nitrate levels, inducible nitric oxide synthase expression, arginase
      activity), but correlated with a marked reduction in HIF-1alpha protein levels.
      In conclusion, these findings suggest that HIF-1alpha and the inflammatory
      response play a significant role in wound healing, and reduced levels of HIF
      1alpha contribute to the impaired healing response post-burn.

PMID- 18615160
TI  - Small doses of aripiprazole augmentation of antidepressant treatment: a report of
      3 cases.

PMID- 18615161
TI  - Hyperosmolar hyperglycemic state in a patient taking risperidone.

PMID- 18615162
TI  - Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and
      depression: a review.
AB  - OBJECTIVE: To review the literature on the co-occurrence of anxiety with
      depressive disorders and the rationale for and use of combination treatment with
      benzodiazepines and selective serotonin reuptake inhibitors/serotonin
      norepinephrine reuptake inhibitors (SSRIs/SNRIs) for treating comorbid anxiety
      and depression. DATA SOURCES: PubMed and PsycINFO were searched using terms
      identified as relevant based on existing practice guidelines. The primary search
      terms were anxiety, anxiety disorders, depression, depressive disorders,
      comorbidity, epidemiology, benzodiazepines, antidepressants, pharmacology,
      clinical trials, and pharmacotherapy. Reference lists of identified articles were
      also reviewed to ensure capture of relevant literature. STUDY SELECTION:
      Publications were selected for inclusion in the review if they applied to adult
      populations and specifically addressed the comorbidity of anxiety and depression,
      their epidemiology, or their management. Case reports and case series were not
      considered for inclusion. DATA EXTRACTION: Each author assessed the publications
      independently for content related to the review topics. Findings considered
      relevant to the clinical understanding and management of comorbid anxiety and
      depression were incorporated into the review. DATA SYNTHESIS: Comorbidity is very
      common among patients with anxiety and depressive disorders, and, even when full
      criteria for 2 separate disorders are not met, subsyndromal symptoms are often
      present. Little controlled research has explored how benzodiazepines and
      SSRIs/SNRIs may be usefully combined, yet their combination is frequently
      employed in clinical practice. Patients with comorbidities are likely to have
      poorer treatment outcomes and have greater utilization of health care resources.
      Currently SSRIs/SNRIs are considered first-line therapy and are effective in both
      anxiety and depressive states. Nevertheless, many patients have only a partial
      response or have difficulty tolerating efficacious doses of antidepressant
      monotherapy. Benzodiazepines appear to improve treatment outcomes when an anxiety
      disorder co-occurs with depression or for depression characterized by anxious
      features. Specifically, they may provide benefits both in terms of speed of
      response and overall response. CONCLUSIONS: Long-term management plans for
      anxiety disorder with or without comorbid depression should include strategies
      for acute or short-term care, long-term maintenance, and episodic or breakthrough
      symptoms. Combination therapy with benzodiazepines and antide-pressants in
      appropriate clinical settings may improve outcomes over monotherapy in some
      patients.

PMID- 18615163
TI  - Diagnosing and managing complicated ADHD.

PMID- 18615164
TI  - Transdermal nicotine in adult ADHD with depression and anxiety.

PMID- 18615165
TI  - Improvement in depressive symptoms with felbamate: a case report.

PMID- 18615166
TI  - Efficacy and safety of antidepressant augmentation with lamotrigine in patients
      with treatment-resistant depression: a randomized, placebo-controlled, double
      blind study.
AB  - OBJECTIVE: This study reports a clinical trial evaluating lamotrigine safety and
      efficacy as an antidepressant augmentation agent in treatment-resistant
      depression, therefore adding more empirical evidence to the limited number of
      studies on the use of lamotrigine. METHOD: A double-blind pilot study was
      conducted between March 2004 and January 2006 with 34 nonbi-polar, nonpsychotic
      patients who had DSM-IV major depressive disorder and were resistant to at least
      2 anti-depressants. The subjects were taking antidepressant therapy and were
      randomly assigned to receive placebo or lamotrigine as an adjunct therapy for 8
      weeks. They were evaluated on a biweekly basis in order to assess the efficacy
      and the safety of the drug. Efficacy was measured with the Montgomery-Asberg
      Depression Rating Scale (MADRS) and the Clinical Global Impressions (CGI) scale.
      Response was defined as a decrease of at least 50% from baseline on the MADRS and
      a final score <= 2 on the CGI. Safety was assessed by keeping record of treatment
      emergent adverse events. RESULTS: The results of the adjunct treatment with
      lamotrigine did not reveal a significant difference according to the MADRS (p =
      .45). No differences between the 2 treatment groups were revealed by the repeated
      measures analysis of variance or by the analysis based on the CGI (p = .45). More
      than 50% of the patients had been treated with at least 3 different anti
      depressants. The most frequent adverse events were nausea, rash, and dyspepsia in
      the lamotrigine group and dizziness and headache in the placebo group.
      CONCLUSIONS: In this study, although it was safe, lamotrigine was not found to be
      an efficient augmentation agent in treatment-resistant depression. Small sample
      size, higher chronicity, and refractoriness may be related to treatment failure.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00652171.

PMID- 18615167
TI  - A survey of primary care provider attitudes and behaviors regarding treatment of
      adult depression: what changes after a collaborative care intervention?
AB  - OBJECTIVE: To assess primary care provider (PCP) attitudes and self-reported
      behavior with regard to identifying and managing depression in adult patients
      before and after a chronic disease/collaborative care intervention. METHOD: A
      self-administered cross-sectional survey was conducted in 6 targeted practices
      among 39 family practice physicians, family nurse practitioners, and residents
      before and after implementation of a depression in primary care project. In this
      project, the sites received tools and training in depression screening and
      guideline-concordant treatment, facilitated referral services for patients to
      access mental health providers, psychiatric phone consultation, patient education
      materials, and services of a depression care manager. The project was conducted
      from June 2003 through June 2006. RESULTS: Comparison of responses prior to and
      after the intervention showed that significantly or nearly significantly larger
      proportions of PCPs endorsed the importance of depression as a patient presenting
      problem (p = .000), increased provision of supportive counseling (p = .13), more
      often identified counseling or therapy as effective (p = .07), and more often
      referred patients to mental health services (p = .001). PCPs also reduced their
      perception that treating depression is time consuming (p = .000). CONCLUSIONS:
      After a chronic disease/collaborative care approach to depression treatment in
      primary care was implemented, PCP attitudes and behaviors about depression
      treatment were significantly modified. More guideline-concordant care, and
      increased collaboration with mental health services, was reported. Implications
      for future primary care depression intervention activities and research are
      discussed.

PMID- 18615169
TI  - Pregabalin augmentation to sertraline-risperidone combination in the treatment of
      obsessive-compulsive disorder.

PMID- 18615168
TI  - Multiple neurologic, psychiatric, and endocrine complaints in a young woman: a
      case discussion and review of the clinical features and management of
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke.

PMID- 18615170
TI  - Substance use disorders in children and adolescents with attention
      deficit/hyperactivity disorder: implications for treatment and the role of the
      primary care physician.
AB  - OBJECTIVES: Review the association between attention-deficit/hyperactivity
      disorder (ADHD) and substance use disorder (SUD) in children and adolescents.
      Discuss treatment implications and the role of the primary care physician in the
      management of this comorbidity. DATA SOURCES: Articles published from 1991 to
      2007 were identified through a MEDLINE search using the search terms attention
      deficit/hyperactivity disorder and substance use disorder. STUDY SELECTION:
      Publications cited include reviews of substance use disorders in children and
      adolescents with ADHD, manuals of diagnostic tests, and 69 studies of substance
      use disorders in children and adolescents with ADHD. No non-English-language
      publications were identified. DATA SYNTHESIS: Recent reports identify SUD in a
      high proportion of respondents with ADHD and ADHD in a high proportion of
      respondents with many types of SUD. Factors that appear to increase the risk for
      SUD include comorbid psychiatric disorders, particularly conduct disorder.
      Pharmacotherapy for ADHD appears not to increase the risk for subsequent SUD.
      Guidelines for the evaluation and treatment of patients with comorbid ADHD and
      SUD are outlined. Psycho-stimulants carry the risk for misuse by both patients
      and family members through diversion. Although nonstimulants such as atomoxetine
      have low abuse potential, they appear to be less efficacious than stimulants.
      Formulations that have the potential to lower the abuse liability of stimulants
      are being developed. These include a transdermal form of methylphenidate that has
      been shown to be efficacious in the treatment of ADHD and a prodrug stimulant,
      lisdexamfetamine, recently approved for the treatment of ADHD. Clinical data
      indicate that lisdexamfetamine is efficacious, and significantly lower likability
      scores were seen with lisdexamfetamine than with equivalent oral doses of d
      amphetamine sulfate. CONCLUSIONS: Pharmacotherapy may reduce the risk for SUD in
      patients with ADHD. Psycho-stimulants remain the first-line therapy for the core
      symptoms of ADHD. New formulations of pharmacologic agents with a reduced
      potential for abuse are being developed.

PMID- 18615171
TI  - Pain complaints in latino adults of mexican origin with and without major
      depressive episode: a cross-sectional study.
AB  - BACKGROUND: The aim of this retrospective, cross-sectional study was to determine
      the prevalence of 5 pain complaints among Latino adults of Mexican origin meeting
      the criteria for major depressive episode (MDE). METHOD: In a mental health
      clinic for the indigent, consecutively evaluated Latino adults of Mexican origin
      received structured diagnostic psychiatric interviews based on modules extracted
      from the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinical
      Version. All were specifically asked whether they had experienced headache,
      backache, abdominal pain, myalgia, or arthralgia "in the last week." Patients
      meeting the criteria for MDE were compared to patients without MDE from the same
      clinic. Associations and statistical significance of the differences between
      groups were determined using logistic regression models. The data were collected
      between August 2003 and November 2004. RESULTS: Two hundred ten patients had an
      MDE, and 35 individuals without an MDE comprised the comparison group. Eighty
      eight percent of the patients with MDE versus 53% of the controls had at least 1
      pain complaint (p < .0001). Patients with MDE were 8.3 times more likely to have
      1 or more pain complaints than the comparison patients (p < .0001). The
      significant relationship between depression and pain applied when we examined
      those with >= 2, >= 3, and >= 4 pain complaints. Twenty-eight percent of the MDE
      subjects had all 5 pain complaints compared to 3% of subjects without MDE (p =
      .013). CONCLUSIONS: The method of assessment of the presence of pain led to the
      detection of a remarkably high prevalence of pain complaints. The findings
      presented have important implications not only for the practice of those who are
      widely recognized as being primary care physicians but also for practitioners of
      all clinical disciplines.

PMID- 18615172
TI  - An open-label, rater-blinded, flexible-dose, 8-week trial of escitalopram in
      patients with major depressive disorder with atypical features.
AB  - OBJECTIVES: Although selective serotonin reuptake inhibitors (SSRIs) have become
      the standard of care for the treatment of major depressive disorder (MDD),
      limited data exist to support their use in MDD with atypical features. The
      current study investigates the efficacy of the SSRI escitalopram in an 8-week,
      open-label, flexible-dose, rater-blinded trial. METHOD: Seventeen DSM-IV MDD
      subjects aged from 18 through 65 years completed screening procedures, provided
      informed consent, and went through a minimum 2-week washout from preexisting
      antide-pressants except fluoxetine (a minimum 4-week wash-out). They subsequently
      received escitalopram (10-20 mg/day) for 8 weeks. The primary efficacy measure
      was a change in score from baseline to end of treatment on the Structured
      Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective
      Disorder version (SIGH-SAD), which includes a set of items for atypical symptoms.
      Secondary efficacy measures were defined as changes from baseline to end of
      treatment in scores on the SIGH-SAD atypical symptoms subscale (consisting of 8
      items specific to atypical features), Beck Depression Inventory-II, Beck Anxiety
      Inventory, Sheehan Disability Scale, and Epworth Sleepiness Questionnaire. The
      study was conducted from October 2005 to November 2006. RESULTS: The mean age was
      43.9 years, and 70.6% of subjects were women. The dropout rate was 11.8% (N =
      2/17). The mean dose of escitalopram was 18.3 mg/day. The total SIGH-SAD score
      (mean +/- SD) reduced by 53.8% from baseline (33.3 +/- 8.2) to end of treatment
      (15.4 +/- 9.4) (t = 4.24, p < .001). The atypical symptoms subscale score reduced
      by 44.5% from baseline (11.0 +/- 4.3) to end of treatment (6.1 +/- 2.8) (t =
      5.26, p = .001). Ten subjects (62.5%) were classified as responders at end of
      treatment as defined by >= 50% reduction in SIGH-SAD total score. Overall,
      escitalopram was well tolerated. CONCLUSIONS: Our preliminary study indicates
      that escitalopram may be beneficial in the treatment of MDD with atypical
      features. Adequately powered, randomized, double-blind, placebo-controlled trials
      are necessary to determine the efficacy of escitalopram in this disorder. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00610506.

PMID- 18615173
TI  - Case report of oculogyric crisis with ziprasidone in a minor.

PMID- 18615174
TI  - Case report of olanzapine-associated elevation of serum creatine kinase in a 16
      year-old boy with heat stroke.

PMID- 18615175
TI  - A case of lamotrigine-associated anticonvulsant hypersensitivity syndrome.

PMID- 18615176
TI  - Implications of pain in generalized anxiety disorder: efficacy of duloxetine.
AB  - OBJECTIVE: To conduct a post hoc evaluation of the prevalence of clinically
      significant pain and the efficacy of duloxetine in patients with generalized
      anxiety disorder (GAD) and concurrent pain. METHOD: Data from two 9- to 10-week
      double-blind, placebo-controlled, randomized clinical trials of duloxetine (60 to
      120 mg) in DSM-IV-defined GAD were analyzed (study 1 was conducted from July 2004
      to September 2005; study 2 was conducted from August 2004 to June 2005). Efficacy
      was assessed with the Hamilton Rating Scale for Anxiety (HAM-A), visual analog
      scales (VAS) for pain, the Hospital Anxiety Depression Scale (HADS), the Clinical
      Global Impressions-Improvement of Illness (CGI-I) scale, the Patient Global
      Impressions-Improvement (PGI-I) scale, and the Sheehan Disability Scale (SDS)
      global functional impairment scale. RESULTS: Of 840 patients randomly assigned to
      treatment, 61.3% (302 duloxetine, 213 placebo) had VAS scores >= 30 mm on at
      least 1 of the pain scales, indicating clinically significant pain. Among those
      patients with concurrent pain at baseline, change from baseline to endpoint in
      the HAM-A total score (42.9% change in mean scores for duloxetine, 31.4% for
      placebo), HADS anxiety scale (40.3% vs. 22.8%), HADS depression scale (36.1% vs.
      20.5%), HAM-A psychic factor (45.9% vs. 29.9%), and SDS global functional
      improvement score (45.5% vs. 22.1%) was significantly (all p's < .001) greater
      for duloxetine compared with placebo. Improvement on the CGI-I (p = .003) and PGI
      I (p < .001) was also significantly greater for duloxetine. Response (HAM-A total
      score decrease >= 50%) (49% vs. 29%) and remission (HAM-A total score <= 7 at
      endpoint) (29% vs. 18%) rates were significantly greater for duloxetine compared
      with placebo (p < .001 and p = .041, respectively). Duloxetine demonstrated
      statistically significantly greater reduction in pain on all 6 VAS pain scales
      (all p's < .001 except headaches with p < .002) (for duloxetine, percent change
      in means from baseline to endpoint ranged from 40.1% to 45.2% across the 6 VAS
      scales; for placebo, 22.0% to 26.3%). CONCLUSION: Duloxetine, relative to
      placebo, improves anxiety symptoms, pain, and functional impairment among
      patients with GAD with concurrent clinically significant pain. TRIAL
      REGISTRATION: clinicaltrials.gov Identifiers: NCT00122824 (study 1) and
      NCT00475969 (study 2).

PMID- 18615177
TI  - The cannabinoid CB2 receptor as a target for inflammation-dependent
      neurodegeneration.
AB  - Endocannabinoids are released following brain injury and may protect against
      excitotoxic damage during the acute stage of injury. Brain injury also activates
      microglia in a secondary inflammatory phase of more widespread damage. Most drugs
      targeting the acute stage are not effective if administered more than 6 hours
      after injury. Therefore, drugs targeting microglia later in the neurodegenerative
      cascade are desirable. We have found that cannabinoid CB2 receptors are up
      regulated during the activation of microglia following brain injury.
      Specifically, CB2-positive cells appear in the rat brain following both hypoxia
      ischemia (HI) and middle cerebral artery occlusion (MCAO). This may regulate post
      injury microglial activation and inflammatory functions. In this paper we review
      in vivo and in vitro studies of CB2 receptors in microglia, including our results
      on CB2 expression post-injury. Taken together, studies show that CB2 is up
      regulated during a process in which microglia become primed to proliferate, and
      then become fully reactive. In addition, CB2 activation appears to prevent or
      decrease microglial activation. In a rodent model of Alzheimer's disease
      microglial activation was completely prevented by administration of a selective
      CB2 agonist. The presence of CB2 receptors in microglia in the human Alzheimer's
      diseased brain suggests that CB2 may provide a novel target for a range of
      neuropathologies. We conclude that the administration of CB2 agonists and
      antagonists may differentially alter microglia-dependent neuroinflammation. CB2
      specific compounds have considerable therapeutic appeal over CB1 compounds, as
      the exclusive expression of CB2 on immune cells within the brain provides a
      highly specialised target, without the psychoactivity that plagues CB1 directed
      therapies.

PMID- 18615178
TI  - The neurobiological bases for development of pharmacological treatments of
      aggressive disorders.
AB  - Violence and aggression are major causes of death and injury, thus constituting
      primary public health problems throughout much of the world costing billions of
      dollars to society. The present review relates our understanding of the
      neurobiology of aggression and rage to pharmacological treatment strategies that
      have been utilized and those which may be applied in the future. Knowledge of the
      neural mechanisms governing aggression and rage is derived from studies in cat
      and rodents. The primary brain structures involved in the expression of rage
      behavior include the hypothalamus and midbrain periaqueductal gray. Limbic
      structures, which include amygdala, hippocampal formation, septal area,
      prefrontal cortex and anterior cingulate gyrus serve important modulating
      functions. Excitatory neurotransmitters that potentiate rage behavior include
      excitatory amino acids, substance P, catecholamines, cholecystokinin,
      vasopressin, and serotonin that act through 5-HT(2) receptors. Inhibitory
      neurotransmitters include GABA, enkephalins, and serotonin that act through 5
      HT(1) receptors. Recent studies have demonstrated that brain cytokines, including
      IL-1beta and IL-2, powerfully modulate rage behavior. IL-1-beta exerts its
      actions by acting through 5-HT(2) receptors, while IL-2 acts through GABAA or
      NK(1) receptors. Pharmacological treatment strategies utilized for control of
      violent behavior have met with varying degrees of success. The most common
      approach has been to apply serotonergic compounds. Others included the
      application of antipsychotic, GABAergic (anti-epileptic) and dopaminergic drugs.
      Present and futures studies on the neurobiology of aggression may provide the
      basis for new and novel treatment strategies for the control of aggression and
      violence as well as the continuation of existing pharmacological approaches.

PMID- 18615179
TI  - Cell and gene therapies for refractory epilepsy.
AB  - Despite recent advances in the development of antiepileptic drugs, refractory
      epilepsy remains a major clinical problem affecting up to 35% of patients with
      partial epilepsy. Currently, there are few therapies that affect the underlying
      disease process. Therefore, novel therapeutic concepts are urgently needed. The
      recent development of experimental cell and gene therapies may offer several
      advantages compared to conventional systemic pharmacotherapy: (i) Specificity to
      underlying pathogenetic mechanisms by rational design; (ii) specificity to
      epileptogenic networks by focal delivery; and (iii) avoidance of side effects. A
      number of naturally occurring brain substances, such as GABA, adenosine, and the
      neuropeptides galanin and neuropeptide Y, may function as endogenous
      anticonvulsants and, in addition, may interact with the process of
      epileptogenesis. Unfortunately, the systemic application of these compounds is
      compromised by limited bioavailability, poor penetration of the blood-brain
      barrier, or the widespread systemic distribution of their respective receptors.
      Therefore, in recent years a new field of cell and gene-based neuropharmacology
      has emerged, aimed at either delivering endogenous anticonvulsant compounds by
      focal intracerebral transplantation of bioengineered cells (ex vivo gene
      therapy), or by inducing epileptogenic brain areas to produce these compounds in
      situ (in vivo gene therapy). In this review, recent efforts to develop GABA-,
      adenosine-, galanin-, and neuropeptide Y- based cell and gene therapies are
      discussed. The neurochemical rationales for using these compounds are discussed,
      the advantages of focal applications are highlighted and preclinical cell
      transplantation and gene therapy studies are critically evaluated. Although many
      promising data have been generated recently, potential problems, such as long
      term therapeutic efficacy, long-term safety, and efficacy in clinically relevant
      animal models, need to be addressed before clinical applications can be
      contemplated.

PMID- 18615180
TI  - Current experimental therapy for Alzheimer's disease.
AB  - In the past decade, enormous efforts have been devoted to understand the genetics
      and molecular pathogenesis of Alzheimer's disease (AD), which has been
      transferred into extensive experimental approaches aimed at reversing disease
      progression. The trend in future AD therapy has been shifted from traditional
      anti-acetylcholinesterase treatment to multiple mechanisms-based therapy
      targeting amyloid plaques formation and amyloid peptides (Abeta)-mediated
      cytotoxicity, and neurofibrillary tangles generation. This review will cover
      current experimental studies with the focus on secretases-based drug development,
      immunotherapy, and anti-neurofibrillary tangles intervention. The outcome of
      these on-going studies may provide high hope that AD can be cured in the future.

PMID- 18615182
TI  - The Role of PPAR-gamma and Its Interaction with COX-2 in Pancreatic Cancer.
AB  - In recent years, the study of the peroxisome proliferators activated receptor
      gamma (PPAR-gamma) as a potential target for cancer prevention and therapy has
      gained a strong interest. However, the overall biological significance of PPAR
      gamma in cancer development and progression is still controversial. While many
      reports documented antiproliferative effects in human cancer cell and animal
      models, several studies demonstrating potential tumor promoting actions of PPAR
      gamma ligands raised considerable concerns about the role of PPAR-gamma in human
      cancers. Controversy also exists about the role of PPAR-gamma in human pancreatic
      cancers. The current review summarizes the data about PPAR-gamma in pancreatic
      cancer and highlights the biologically relevant interactions between the
      cyclooxygenase and PPAR system.

PMID- 18615184
TI  - PPARgamma and Apoptosis in Cancer.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand binding
      transcription factors which function in many physiological roles including lipid
      metabolism, cell growth, differentiation, and apoptosis. PPARs and their ligands
      have been shown to play a role in cancer. In particular, PPARgamma ligands
      including endogenous prostaglandins and the synthetic thiazolidinediones (TZDs)
      can induce apoptosis of cancer cells with antitumor activity. Thus, PPARgamma
      ligands have a potential in both chemoprevention and therapy of several types of
      cancer either as single agents or in combination with other antitumor agents.
      Accordingly, the involvement of PPARgamma and its ligands in regulation of
      apoptosis of cancer cells have been extensively studied. Depending on cell types
      or ligands, induction of apoptosis in cancer cells by PPARgamma ligands can be
      either PPARgamma-dependent or -independent. Through increasing our understanding
      of the mechanisms of PPARgamma ligand-induced apoptosis, we can develop better
      strategies which may include combining other antitumor agents for PPARgamma
      targeted cancer chemoprevention and therapy. This review will highlight recent
      research advances on PPARgamma and apoptosis in cancer.

PMID- 18615181
TI  - Parkinson's disease: genetics and beyond.
AB  - Parkinson's disease (PD) is characterized clinically by resting tremor, rigidity,
      bradykinesia and postural instability due to progressive and selective loss of
      dopamine neurons in the ventral substantia nigra, with the presence of
      ubiquitinated protein deposits called Lewy bodies in the neurons. The
      pathoetiology of cell death in PD is incompletely understood and evidence
      implicates impaired mitochondrial complex I function, altered intracellular redox
      state, activation of proapoptotic factors and dysfunction of ubiquitinproteasome
      pathway. Now it is believed that genetic aberration, an environmental toxin or
      combination of both leads to a cascade of events culminating in the destruction
      of myelinated brainstem catecholaminergic neurons. Also the role of production of
      significant levels of abnormal proteins, which may misfold, aggregate and
      interfere with intracellular processes causing cytotoxicity has recently been
      hypothesized. In this article, the diverse pieces of evidence that have linked
      the various factors responsible for the pathophysiology of PD are reviewed with
      special emphasis to various candidate genes and proteins. Furthermore, the
      present therapeutic strategies and futuristic approaches for the pharmacotherapy
      of PD are critically discussed.

PMID- 18615185
TI  - Vesicoureteral reflux in the child with lazy bladder syndrome: the infrequent
      voider.
AB  - The Infrequent Voider Syndrome or Lazy Bladder Syndrome in children is
      characterized by a large capacity bladder, frequently associated with a
      significant volume of residual urine. Usually these patients arrive at medical
      examination with a history of recurrent urinary infections but without anomalies
      in the upper urinary tract. We report about a young girl affected by one-sided 2
      degrees degree vesico-ureteral reflux due to Lazy Bladder Syndrome that had never
      been diagnosed before. This patient has been submitted to a prompt bladder
      training and seems presently to have at last gained a physiological micturition
      after 9 months of follow-up, without actual evidence of vesicoureteral reflux.
      Therefore we must stress that it is prominently important considering about
      infrequent micturition in a paediatric case history or a large capacity bladder,
      possible presence of bladder dysfunction and vesicoureteral reflux too.

PMID- 18615183
TI  - The PPAR-gamma Agonist 15-Deoxy-Delta-Prostaglandin J(2) Attenuates Microglial
      Production of IL-12 Family Cytokines: Potential Relevance to Alzheimer's Disease.
AB  - Accumulation of amyloid-beta peptide (Abeta) appears to contribute to the
      pathogenesis of Alzheimer's disease (AD). Therapeutic hope for the prevention or
      removal of Abeta deposits has been placed in strategies involving immunization
      against the Abeta peptide. Initial Abeta immunization studies in animal models of
      AD showed great promise. However, when this strategy was attempted in human
      subjects with AD, an unacceptable degree of meningoencephalitis occurred. It is
      generally believed that this adverse outcome resulted from a T-cell response to
      Abeta. Specifically, CD4(+) Th1 and Th17 cells may contribute to severe CNS
      inflammation and limit the utility of Abeta immunization in the treatment of AD.
      Interleukin (IL)-12 and IL-23 play critical roles in the development of Th1 and
      Th17 cells, respectively. In the present study, Abeta(1-42) synergistically
      elevated the expression of IL-12 and IL-23 triggered by inflammatory activation
      of microglia, and the peroxisome proliferator-activated receptor (PPAR)-gamma
      agonist 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) effectively blocked the
      elevation of these proinflammatory cytokines. Furthermore, 15d-PGJ(2) suppressed
      the Abeta-related synergistic induction of CD14, MyD88, and Toll-like receptor 2,
      molecules that play critical roles in neuroinflammatory conditions. Collectively,
      these studies suggest that PPAR-gamma agonists may be effective in modulating the
      development of AD.

PMID- 18615186
TI  - Use of a smartphone for improved self-management of pulmonary rehabilitation.
AB  - Patients suffering from chronic respiratory disease need to follow a
      rehabilitative exercise programme, in order to self-manage their illness and
      improve quality of life. Adherence to the programme is highly dependent on
      professional support from a physiotherapist and hence declines when patients seek
      to self-manage in the home. A number of requirements were identified for a
      Smartphone-based application in which patients are supported remotely and given
      automatic feedback during exercise. An application is described which will
      improve adherence during pulmonary rehabilitation.

PMID- 18615188
TI  - A Novel Mechanism of PPARgamma Regulation of TGFbeta1: Implication in Cancer
      Biology.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) and retinoic acid X
      receptor (RXR) heterodimer, which regulates cell growth and differentiation,
      represses the TGFbeta1 gene that encodes for the protein involved in cancer
      biology. This review will introduce the novel mechanism associated with the
      inhibition of the TGFbeta1 gene by PPARgamma activation, which regulates the
      dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of
      TGFbeta1 by PPARgamma activators can be applied for treating TGFbeta1-induced
      pathophysiologic disorders such as cancer metastasis and fibrosis. In this
      article, we will discuss the opposing effects of TGFbeta on tumor growth and
      metastasis, and address the signaling pathways regulated by PPARgamma for tumor
      progression and suppression.

PMID- 18615187
TI  - Macrophages, PPARs, and Cancer.
AB  - Mononuclear phagocytes often function as control switches of the immune system,
      securing the balance between pro- and anti-inflammatory reactions. For this
      purpose and depending on the activating stimuli, these cells can develop into
      different subsets: proinflammatory classically activated (M1) or anti
      inflammatory alternatively activated (M2) macrophages. The expression of the
      nuclear peroxisome proliferator-activated receptors (PPARs) is regulated by M1-
      or M2-inducing stimuli, and these receptors are generally considered to
      counteract inflammatory M1 macrophages, while actively promoting M2 activation.
      This is of importance in a tumor context, where M1 are important initiators of
      inflammation-driven cancers. As a consequence, PPAR agonists are potentially
      usefull for inhibiting the early phases of tumorigenesis through their
      antagonistic effect on M1. In more established tumors, the macrophage phenotype
      is more diverse, making it more difficult to predict the outcome of PPAR agonism.
      Overall, in our view current knowledge provides a sound basis for the clinical
      evaluation of PPAR ligands as chemopreventive agents in chronic inflammation
      associated cancer development, while cautioning against the unthoughtful
      application of these agents as cancer therapeutics.

PMID- 18615189
TI  - Bioinformatic tools for inferring functional information from plant microarray
      data II: Analysis beyond single gene.
AB  - While it is possible to interpret microarray experiments a single gene at a time,
      most studies generate long lists of differentially expressed genes whose
      interpretation requires the integration of prior biological knowledge. This prior
      knowledge is stored in various public and private databases and covers several
      aspects of gene function and biological information. In this review, we will
      describe the tools and places where to find prior accurate biological information
      and how to process and incorporate them to interpret microarray data analyses.
      Here, we highlight selected tools and resources for gene class level ontology
      analysis (Section 2), gene coexpression analysis (Section 3), gene network
      analysis (Section 4), biological pathway analysis (Section 5), analysis of
      transcriptional regulation (Section 6), and omics data integration (Section 7).
      The overall goal of this review is to provide researchers with tools and
      information to facilitate the interpretation of microarray data.

PMID- 18615190
TI  - Effect of semen on vaginal fluid cytokines and secretory leukocyte protease
      inhibitor.
AB  - The presence of semen in vaginal fluid, as identified by an acid phosphatase spot
      test, does not influence vaginal proinflammatory cytokine concentrations.
      OBJECTIVE: Determine whether semen, as detected by acid phosphatase, influences
      vaginal cytokines or secretory leukocyte protease inhibitor concentrations.
      METHODS: 138 pregnant women had vaginal fluid collected for Gram stain, acid
      phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin
      6, interleukin-8, and secretory leukocyte protease inhibitor measurement by
      enzyme immunoassay. Results for women with and without acid phosphatase were
      compared by Mann-Whitney test. RESULTS: Of 138 subjects, 28 (20%) had acid
      phosphatase detected; of these, only 19 (68%) reported recent intercourse and 3
      (11%) had sperm seen on Gram stain. There were no significant differences in
      proinflammatory cytokine concentrations; however, secretory leukocyte protease
      inhibitor concentrations were significantly higher among women with acid
      phosphatase. CONCLUSIONS: Proinflammatory cytokine measurement does not appear to
      be affected by the presence of semen, but secretory leukocyte protease inhibitor
      is significantly higher when semen is present. Detection of semen by acid
      phosphatase was associated with higher vaginal SLPI concentrations, however, the
      presence of semen did not appear to influence vaginal proinflammatory cytokine
      concentrations.

PMID- 18615191
TI  - A survey of insulin-dependent diabetes-part I: therapies and devices.

PMID- 18615192
TI  - Pathophysiological Roles of PPARgamma in Gastrointestinal Epithelial Cells.
AB  - Although the highest levels of PPARgamma expression in the body have been
      reported in the gastrointestinal epithelium, little is known about the
      physiological functions of that receptor in the gut. Moreover, there is
      considerable controversy concerning the effects of thiazolidinedione PPARgamma
      agonists on the two major diseases of the gastrointestinal track: colorectal
      cancer and inflammatory bowel disease. We will undertake to review both
      historical and recently published data with a view toward summarizing what is
      presently known about the roles of PPARgamma in both physiological and
      pathological processes in the gastrointestinal epithelium.

PMID- 18615193
TI  - Advances in nonnegative matrix and tensor factorization.

PMID- 18615194
TI  - Anxiety in children undergoing VCUG: sedation or no sedation?
AB  - BACKGROUND: Voiding cystourethrograms are distressing for children and parents.
      Nonpharmacological methods reduce distress. Pharmacological interventions for
      VCUG focus on sedation as well as analgesia, anxiolysis, and amnesia. Sedation
      has cost, time, and safety issues. Which agents and route should we use? Are we
      sure that sedation does not influence the ability to diagnose vesicoureteric
      reflux? METHODS: Literature search of Medline, EMBASE, and the Cochrane Database.
      Review of comparative studies found. RESULTS: Seven comparative studies including
      two randomised controlled trials were reviewed. Midazolam given orally (0.5-0.6
      mg/kg) or intranasally (0.2 mg/kg) is effective with no apparent effect on
      voiding dynamics. Insufficient evidence to recommend other sedating agents was
      found. Deeper sedating agents may interfere with voiding dynamics. CONCLUSION:
      Midazolam reduces the VCUG distress, causes amnesia, and does not appear to
      interfere with voiding dynamics. Midazolam combined with simple analgesia is an
      effective method to reduce distress to children undergoing VCUG.

PMID- 18615195
TI  - The fetal allograft revisited: does the study of an ancient invertebrate species
      shed light on the role of natural killer cells at the maternal-fetal interface?
AB  - Human pregnancy poses a fundamental immunological problem because the placenta
      and fetus are genetically different from the host mother. Classical
      transplantation theory has not provided a plausible solution to this problem.
      Study of naturally occurring allogeneic chimeras in the colonial marine
      invertebrate, Botryllus schlosseri, has yielded fresh insight into the primitive
      development of allorecognition, especially regarding the role of natural killer
      (NK) cells. Uterine NK cells have a unique phenotype that appears to parallel
      aspects of the NK-like cells in the allorecognition system of B. schlosseri. Most
      notably, both cell types recognize and reject "missing self" and both are
      involved in the generation of a common vascular system between two individuals.
      Chimeric combination in B. schlosseri results in vascular fusion between two
      individual colonies; uterine NK cells appear essential to the establishment of
      adequate maternal-fetal circulation. Since human uterine NK cells appear to de
      emphasize primary immunological function, it is proposed that they may share the
      same evolutionary roots as the B. schlosseri allorecognition system rather than a
      primary origin in immunity.

PMID- 18615197
TI  - Anticancer Activity of Ag(I) N-Heterocyclic Carbene Complexes Derived from 4,5
      Dichloro-1H-Imidazole.
AB  - A class of Ag(I) N-heterocyclic carbene silver complexes, 1-3, derived from 4,5
      dichloro-1H-imidazole has been evaluated for their anticancer activity against
      the human cancer cell lines OVCAR-3 (ovarian), MB157 (breast), and Hela
      (cervical). Silver complexes 1-3 are active against the ovarian and breast cancer
      cell lines. A preliminary in vivo study shows 1 to be active against ovarian
      cancer in mice. The results obtained in these studies warrant further
      investigation of these compounds in vivo.

PMID- 18615196
TI  - The Role of PPAR Ligands in Controlling Growth-Related Gene Expression and their
      Interaction with Lipoperoxidation Products.
AB  - Peroxisome proliferators-activated receptors (PPARs) are ligand-activated
      transcription factors that belong to the nuclear hormone receptor superfamily.
      The three PPAR isoforms (alpha, gamma and beta/delta) have been found to play a
      pleiotropic role in cell fat metabolism. Furthermore, in recent years, evidence
      has been found regarding the antiproliferative, proapoptotic, and differentiation
      promoting activities displayed by PPAR ligands, particularly by PPARgamma
      ligands. PPAR ligands affect the expression of different growth-related genes
      through both PPAR-dependent and PPAR-independent mechanisms. Moreover, an
      interaction between PPAR ligands and other molecules which strengthen the effects
      of PPAR ligands has been described. Here we review the action of PPAR on the
      control of gene expression with particular regard to the effect of PPAR ligands
      on the expression of genes involved in the regulation of cell-cycle,
      differentiation, and apoptosis. Moreover, the interaction between PPAR ligands
      and 4-hydroxynonenal (HNE), the major product of the lipid peroxidation, has been
      reviewed.

PMID- 18615198
TI  - Do PPARgamma Ligands Suppress the Growth of Cholangiocarcinoma or the
      Cholangiohepatitis Induced by the Tumor?
AB  - Cholangiocarcinoma is a predominantly fatal cancer, which can be difficult to
      treat. It has been reported that the administration of pioglitazone temporarily
      improved not only diabetic control, but also bile duct carcinoma-induced
      cholangiohepatitis. Pioglitazone is considered to have both direct and indirect
      mechanisms of action on the tumor-related hepatitis. Several molecules induced by
      thiazolidinedione, including Smad pathway-related molecules, adipokines, and
      other lipid metabolism-related proteins, may directly or indirectly suppress
      tumor development and/or tumor-induced cholangiohepatitis. Although the most
      frequent and critical side effect of thiazolidinedione is drug-induced hepatitis,
      it can probably be avoided by careful monitoring of serum hepatic enzyme levels.
      Thiazolidinedione should be considered for management of tumor-induced hepatitis
      in the presence of diabetes unless severe side effects occur.

PMID- 18615200
TI  - A tamper-resistant and portable healthcare folder.
AB  - Electronic health record (EHR) projects have been launched in most developed
      countries to increase the quality of healthcare while decreasing its cost. The
      benefits provided by centralizing the healthcare information in database systems
      are unquestionable in terms of information quality, availability, and protection
      against failure. Yet, patients are reluctant to give to a distant server the
      control over highly sensitive data (e.g., data revealing a severe or shameful
      disease). This paper capitalizes on a new hardware portable device, associating
      the security of a smart card to the storage capacity of a USB key, to give back
      to the patient the control over his medical data. This paper shows how this
      device can complement a traditional EHR server to (1) protect and share highly
      sensitive data among trusted parties and (2) provide a seamless access to the
      data even in disconnected mode. The proposed architecture is experimented in the
      context of a medicosocial network providing medical care and social services at
      home for elderly people.

PMID- 18615199
TI  - Complementary roles of hippocampus and medial entorhinal cortex in episodic
      memory.
AB  - Spatial mapping and navigation are figured prominently in the extant literature
      that describes hippocampal function. The medial entorhinal cortex is likewise
      attracting increasing interest, insofar as evidence accumulates that this area
      also contributes to spatial information processing. Here, we discuss recent
      electrophysiological findings that offer an alternate view of hippocampal and
      medial entorhinal function. These findings suggest complementary contributions of
      the hippocampus and medial entorhinal cortex in support of episodic memory,
      wherein hippocampal networks encode sequences of events that compose temporally
      and spatially extended episodes, whereas medial entorhinal networks disambiguate
      overlapping episodes by binding sequential events into distinct memories.

PMID- 18615201
TI  - Disturbed alpha-cell function in mice with beta-cell specific overexpression of
      human islet amyloid polypeptide.
AB  - Exogenous administration of islet amyloid polypeptide (IAPP) has been shown to
      inhibit both insulin and glucagon secretion. This study examined alpha-cell
      function in mice with beta-cell specific overexpression of human IAPP (hIAPP)
      after an oral protein gavage (75 mg whey protein/mouse). Baseline glucagon levels
      were higher in transgenic mice (41 +/- 4.0 pg/mL, n = 6) than in wildtype animals
      (19 +/- 5.1 pg/mL, n = 5, P = .015). In contrast, the glucagon response to
      protein was impaired in transgenic animals (21 +/- 2.7 pg/mL in transgenic mice
      versus 38 +/- 5.7 pg/mL in wildtype mice at 15 minutes; P = .027). Baseline
      insulin levels did not differ between the groups, while the insulin response, as
      the glucagon response, was impaired after protein challenge (P = .018). Glucose
      levels were not different between the groups and did not change significantly
      after protein gavage. Acetaminophen was given through gavage to the animals (2
      mg/mouse) to estimate gastric emptying. The plasma acetaminophen profile was
      similar in the two groups of mice. We conclude that disturbances in glucagon
      secretion exist in mice with beta-cell specific overexpression of human IAPP,
      which are not secondary to changes in gastric emptying. The reduced glucagon
      response to protein challenge may reflect a direct inhibitory influence of hIAPP
      on glucagon secretion.

PMID- 18615202
TI  - Microarray analysis of host gene expression for comparison between naive and HSV
      1 latent rabbit trigeminal ganglia.
AB  - PURPOSE: To analyze the rabbit host global gene expression patterns in uninfected
      and herpes simplex virus type 1 (HSV-1) latent trigeminal ganglia (TG) for
      identification of host response-initiated transcriptional changes during the
      maintenance of viral latency. METHODS: The corneas of eight-week-old New Zealand
      White rabbits were scarified and inoculated with HSV-1 strain McKrae, 5x10(5)
      plaque forming units/eye. Corneal infection was verified by slit-lamp
      examination. Prior to sacrifice at 30 days post infection, ocular swabs confirmed
      no infectious virus was present. TG were aseptically removed from rabbits and
      placed in RNA stabilization solution. Host RNA was isolated from two groups of
      TG, uninfected and HSV-1 latent infected, and used to create labeled cRNA.
      Labeled cRNA was hybridized to two new and novel custom oligonucleotide rabbit
      arrays, containing a total of 3,123 probes for rabbit genes. RESULTS: The rabbit
      TG expressed approximately 80% of genes out of a total of 3,123. A one-way ANOVA
      performed on the log2 transformed signal ratios showed 611 genes were
      significantly altered (p< or =0.05) in HSV-1 latent TG. These genes, if
      annotated, were separated by biologic process categories. Five broad categories
      were most heavily represented: protein processing, carbohydrate processing, cell
      adhesion, apoptosis, and host defense and immune response. Sixty of the
      significantly altered genes were found to be altered by more than 2 fold, and
      five were altered by more than 4 fold. The genes altered by more than 4 fold were
      all upregulated and related to host defense and immune response. Viral latency
      had a large effect on protein processing. Of the differentially expressed genes
      with an assigned biologic process, 90/349 (25.7%) were associated with protein
      processing. The next most populated categories were carbohydrate metabolism
      39/349 (11.1%) and host defense and immune response 17/349 (4.9%). CONCLUSIONS:
      The results of this microarray study demonstrate that host gene expression is
      altered in the HSV-1 latent rabbit TG. The shift in molecular processes at a
      pathway level reveals the presence of potential therapeutic significance inherent
      in the maintenance of HSV-1 latency. This is the first large-scale rabbit gene
      expression study, using microarray analysis, that documents the involvement of
      host immunity in maintaining HSV-1 latency.

PMID- 18615203
TI  - Patterns of crystallin distribution in porcine eye lenses.
AB  - PURPOSE: To measure the protein distribution patterns in single young porcine
      lenses. METHODS: Twenty fresh porcine lenses from 5 to 6 months old animals were
      fractionated into 8-10 concentric fractions by controlled dissolution in
      phosphate buffer. Proportions of soluble and insoluble protein were determined by
      Bradford assay. Water-soluble proteins in all layers were separated into HMW,
      MMW, and LMW fractions by size-exclusion HPLC and constituents of each class
      further characterized by SDS gel electrophoresis, as were the water-insoluble
      proteins. Size-exclusion fractions were further separated by reverse-phase HPLC
      and the molecular masses of each peak determined by MALDI-TOF mass spectrometry.
      RESULTS: The major soluble proteins in the porcine lens are beta-crystallins.
      They comprise around 45% of the total protein in the outer lens decreasing
      gradually to 35% in the central region. Soluble alpha-crystallins vary from 35%
      to 22% from outer to inner lens. The proportion of soluble gamma-crystallin
      levels, substantially lower than that of the other protein classes, increases
      gradually with progression into the lens center. Insoluble protein levels also
      increase from outer to inner lens layers. CONCLUSIONS: In the young porcine lens,
      there is relative constancy in the levels of all three crystallin classes in the
      outer lens with alpha- and beta-crystallins representing the predominant protein
      classes. The increase in gamma-crystallin in the inner lens may contribute to the
      refractive index gradient.

PMID- 18615204
TI  - Mitomycin C induces apoptosis in cultured corneal fibroblasts derived from type
      II granular corneal dystrophy corneas.
AB  - PURPOSE: The present study investigated the effect of mitomycin C (MMC) on cell
      viability, apoptosis, and transforming growth factor beta-induced protein
      (TGFBIp) expression in cultured normal corneal fibroblasts and heterozygote or
      homozygote granular corneal dystrophy type II (GCD II) corneal fibroblasts.
      METHODS: Keratocytes were obtained from normal cornea or from heterozygote or
      homozygote GCD II patients after lamellar or penetrating keratoplasty. To measure
      cell viability, corneal fibroblasts were incubated with 0.02% MMC for 3 h, 6 h,
      and 24 h or with 0%, 0.01%, 0.02%, and 0.04% MMC for 24 h and then tested using
      lactate dehydrogenase (LDH) and 3-[4,5-demethylthiazol-2,5-diphenyl-2H
      tetrazolium bromide] (MTT) assays. To measure apoptosis, cells were analyzed by
      FACS analysis and annexin V staining. Bcl-xL, Bax, and TGFBI mRNA expression was
      measured using reverse transcription polymerase chain reaction (RT-PCR) assays.
      Cellular and media levels of TGFBIp protein were measured by immunoblotting.
      RESULTS: MTT and LDH assays showed that MMC reduced cell viability in all three
      cell types in a dose-dependent and time-dependent manner (p<0.05). FACS analysis
      and annexin V staining showed that MMC caused apoptosis with GCD II homozygote
      cells being most affected. RT-PCR analysis showed that MMC decreased Bcl-xL mRNA
      expression and increased Bax mRNA expression in all cell types. RT-PCR and
      immunoblotting analysis showed that MMC reduced TGFBI mRNA levels and cellular
      and media TGFBIp protein levels in all cell types. CONCLUSIONS: MMC induced
      apoptosis, and the effects of MMC were greatest in GCD II homozygote cells. MMC
      also reduced the production of TGFBIp in all three types of corneal fibroblasts.
      These findings may explain the additional therapeutic effect of MMC in GCD II
      patients.

PMID- 18615205
TI  - Late-onset bilateral lens dislocation and glaucoma associated with a novel
      mutation in FBN1.
AB  - PURPOSE: To describe the clinical and genetic findings in one Chinese family with
      late-onset bilateral lens dislocation and secondary glaucoma. METHODS: One family
      including three affected members and 16 unaffected family members was examined
      clinically. After informed consent was obtained, genomic DNA was extracted from
      venous blood of all participants. Linkage analysis was performed with two
      microsatellite markers around the fibrillin-1 (FBN1) gene (D15S992 and D15S126).
      Mutation screening was performed using direct DNA sequence analysis and single
      strand conformation polymorphism (SSCP). RESULTS: Clinical examination and
      pedigree analysis revealed that four members in three generations were affected
      by late-onset lens dislocation and secondary glaucoma but had no signs of
      cardiovascular abnormality or abnormal skeletal features. By genotyping, the
      family showed the linkage to FBN1 on 15q21.1. After mutation screening analysis
      on 65 exons of FBN1, a novel heterozygous missense mutation, c.2860C>T (R954C),
      was detected. This mutation cosegregated with the disease phenotype in the family
      and was not found in 100 normal controls. CONCLUSIONS: Late-onset isolated
      ectopia lentis with secondary glaucoma is consistent with a novel mutation in
      FBN1. Our finding expands the spectrum of FBN1 mutations and is useful for
      further genetic consultation and genetic diagnosis.

PMID- 18615206
TI  - An R124C mutation in TGFBI caused lattice corneal dystrophy type I with a
      variable phenotype in three Chinese families.
AB  - PURPOSE: A genetic and clinical study of three unrelated Chinese pedigrees with a
      variable phenotype of lattice corneal dystrophy type I (LCD I). METHODS: The eyes
      of the patients were examined by slit lamp microscopy, and other clinical records
      were also collected. Genomic DNA was extracted from peripheral leukocytes of the
      affected patients and their family members. Exons of the transforming growth
      factor beta induced TGFBI gene were amplified by polymerase chain reaction and
      directly sequenced to verify the mutation. Fifty healthy volunteers were analyzed
      as normal controls. RESULTS: Variable atypical clinical features of LCD I were
      found by slit lamp microscopy in these three Chinese pedigrees. A heterozygous
      single base-pair transition from C to T (C417T), leading to amino acid
      substitution (R124C) in the encoded TGFBI protein, was detected in all of the
      affected patients. No mutation was found in unaffected family members and 50
      normal controls. CONCLUSIONS: Clinical features of Chinese patients with the same
      R124C mutation are quite variable even within the same family. Molecular genetic
      analysis of TGFBI can offer a rapid, accurate diagnosis of patients with atypical
      corneal dystrophies.

PMID- 18615207
TI  - The coordination chemistry of nitrosyl in cyanoferrates. An exhibit of
      bioinorganic relevant reactions.
AB  - Sodium nitroprusside (SNP, Na(2)[Fe(CN)(5)(NO)].2H(2)O) is a widely used NO-donor
      hypotensive agent, containing the formally described nitrosonium (NO(+)) ligand,
      which may be redox-interconverted to the corresponding one-electron (NO) and two
      electron (NO(-)/HNO) reduced bound species. Thus, the chemistry of the three
      nitrosyl ligands may be explored with adequate, biologically relevant substrates.
      The nitrosonium complex, [Fe(CN)(5)(NO)](2-), is formed through a reductive
      nitrosylation reaction of [Fe(III)(CN)(5)(H(2)O)](2-) with NO, or, alternatively,
      through the coordination of NO(2)(-) to [Fe(II)(CN)(5)(H(2)O)](3-) and further
      proton-assisted dehydration. It is extremely inert toward NO(+)-dissociation, and
      behaves as an electrophile toward different bases: OH(-), amines, thiolates, etc.
      Also, SNP releases NO upon UV-vis photo-activation, with formation of
      [Fe(III)(CN)(5)(H(2)O)](2-). The more electron rich [Fe(CN)(5)(NO)](3-) may be
      prepared from [Fe(II)(CN)(5)(H(2)O)](3-) and NO, and is also highly inert toward
      the dissociation of NO (k = 1.6 x 10(-5) s(-1), 25.0 degrees C, pH 10.2). It
      reacts with O(2) leading to SNP, with the intermediacy of a peroxynitrite adduct.
      The [Fe(CN)(5)(NO)](3-) ion is labile toward the release of trans-cyanide,
      forming the [Fe(CN)(4)(NO)](2-) ion. Both complexes exist in a pH-dependent
      equilibrium, and decompose thermally in the hours time scale, releasing cyanides
      and NO. The latter may further bind to [Fe(CN)(4)(NO)](2-) with formation of a
      singlet dinitrosyl species, [Fe(CN)(4)(NO)(2)](2-), which in turn is unstable
      toward disproportionation into SNP and N(2)O, and toward the parallel formation
      of a tetrahedral paramagnetic dinitrosyl compound, [Fe(CN)(2)(NO)(2)]. Emerging
      studies with the putative nitroxyl complex, [Fe(CN)(5)(HNO)](3-), should allow
      for a complete picture of the three nitrosyl ligands in the same pentacyano
      fragment. The present Perspective, based on an adequate characterization of
      structural and spectroscopic properties, will focus on the kinetic and
      mechanistic description of the above mentioned reactions, which display a
      versatile scenario, fundamentally related to the biologically relevant processes
      associated with NO reactivity.

PMID- 18615208
TI  - Pd-catalyzed diarylation of aniline--a way to a non-linear bis(terpyridyl) ligand
      providing increased electronic communication.
AB  - An amine-linked bis(terpyridyl) ligand, prepared via Pd-catalyzed diarylation of
      aniline, mediates unusually strong metal-metal interaction in its Ru(2)
      polypyridyl complex.

PMID- 18615209
TI  - Assembly of a two-dimensional oxalate-bridged heterometallic Co(II)(3)Cr(III)(2)
      coordination polymer.
AB  - Reaction of CoCl(2).4H(2)O with Ag(3)[Cr(ox)(3)] (3 : 2 mol/mol) in methanol
      gives rise to an oxalate-bridged complex [Co(MeOH)(2)](3)[Cr(ox)(3)](2).6MeOH
      that consists of a rare cloverleaf-like layered structure (12,3-net).
      Ferromagnetic coupling is operative between the adjacent metal ions through the
      oxalate bridges.

PMID- 18615210
TI  - Heterogeneous catalysts for the controlled ring-opening polymerisation of rac
      lactide and homogeneous silsesquioxane model complexes.
AB  - In this communication we report, for the first time, the ring-opening
      polymerisation in the melt of rac-lactide with heterogeneous catalysts.
      Homogeneous model systems based on silsesquioxanes have been prepared for
      comparison.

PMID- 18615211
TI  - Cyano-bridged coordination polymer nanoparticles with high nuclear relaxivity:
      toward new contrast agents for MRI.
AB  - New water-soluble paramagnetic Gd-containing cyano-bridged metallic coordination
      polymer nanoparticles with a chitosan shell show high nuclear relaxivity in
      acidic water which is up to six times higher than that of the actually used Gd
      chelates.

PMID- 18615212
TI  - Towards inert and preorganized d-block-containing receptors for trivalent
      lanthanides: the synthesis and characterization of triple-helical monometallic
      Os(II) and bimetallic Os(II)-Ln(III) complexes.
AB  - The mononuclear Os(II) complex [Os()(3)](PF(6))(2) ( = 5-methyl(1
      methylbenzimidazol-2-yl)pyridine) is an obvious candidate for the design of an
      inert d-block-based tripodal receptor capable of binding and photosensitizing
      trivalent lanthanides (Ln(III)). It has thus been prepared and its two
      enantiomeric meridional (Delta-mer and Lambda-mer) and facial (rac-fac) isomers
      have been separated by ion-exchange chromatography. The optical isomers have been
      characterized by CD spectroscopy and assignments of absolute configuration
      confirmed by an X-ray crystallographic study of Lambda-mer
      [Os()(3)](PF(6))(2).1.5MeCN (monoclinic, P2(1), Z = 4). Comparison of the latter
      structure with that of racemic fac-[Os()(3)](PF(6))(2) (monoclinic, C2/c, Z = 8)
      and [Os(bipy)(3)](PF(6))(2) (where bipy = 2,2'-bipyridine) shows minimal
      structural variations, but differences are observed in the photophysical and
      electrochemical properties of the respective compounds. Luminescence emissions
      from Os(II) complexes of are typically lower in energy, with shorter lifetimes
      and lower quantum yields than their bipy analogues, whilst metal-centred
      oxidation processes are more facile due to the enhanced pi-donor ability of . The
      key relationships between these parameters are discussed. Finally, though
      challenged by (i) the low reactivity of many osmium precursors and (ii) the
      irreversible formation of competing side products, the synthesis and purification
      of the heterobimetallic triple-stranded helicate HHH-[OsLu()(3)](CF(3)SO(3))(5)
      has been realised, in which is a segmental ligand containing the same bidentate
      unit as that found in further connected to a tridentate binding site adapted for
      complexing Ln(III). Its solid-state structure has been established by X-ray
      crystallography (triclinic, P1, Z = 2).

PMID- 18615213
TI  - Synthesis, structure and isomerization of arylphosphoranes with anti-apicophilic
      bonding modes using a novel bidentate ligand with two C(2)F(5) groups.
AB  - A series of anti-apicophilic pentacoordinate phosphoranes (with one chelating
      substituent in an O-equatorial, C-apical bonding mode at pentacoordinated
      phosphorus atom) bearing a para-substituted aryl group (-C(6)H(4)(p-X); X = H,
      CF(3), F, OMe) or a mesityl (2,4,6-trimethylphenyl) group were isolated using a
      novel bulky bidentate ligand with two C(2)F(5) groups. These phosphoranes were
      stable to isomerization at room temperature, and quantitatively converted into
      the corresponding more stable isomers (O-apical) at elevated temperatures in
      solution. On the basis of a kinetic study, the free energy of activation
      (DeltaG(double dagger)) of the stereomutation of the O-equatorial
      mesitylphosphorane to its O-apical isomer was higher than that of the CF(3)
      derivative by 2.6 kcal mol(-1), giving rise to a further example of the steric
      effect of the C(2)F(5) group to freeze the isomerization of the pentacoordinate
      phosphorus compounds. Kinetic measurements of the isomerization of the O
      equatorial ortho-unsubstituted derivatives (-C(6)H(4)(p-X)) to the corresponding
      O-apical isomers suggested that the O-equatorial isomers were stabilized by the
      pi --> sigma*(P-O) interaction in the ground state.

PMID- 18615214
TI  - A decagallane(6) cluster Ga(10)[Si(CMe(3))(3)](6) with an unprecedented
      structure.
AB  - The decagallane(6) Ga(10)R'(6) [R' = Si(CMe(3))(3)] adopts a quite unusual
      structure, which might be described as being derived from a pentagonal
      bipyramidal core, which is threefold capped. An alternative description is that
      of a conjuncto-cluster. The structure of the anionic cluster [Ga(10)R'(6)](-) as
      well as that of Ga(10)R''(6) [R'' = Si(SiMe(3))(3)] are described as being built
      of fused octahedra. Thus, this family of decagallanes is unique in showing
      structural isomers in the cluster core, giving hints to the pathways of formation
      of these clusters, too. The novel cluster compound is characterized by X-ray
      crystallography. Isomeric decagallanes(6) and structural changes on reduction are
      studied by DFT methods.

PMID- 18615215
TI  - Imidazolium-based macrocycles as multisignaling chemosensors for anions.
AB  - A series of structurally novel anion receptors , , and in which a ferrocene unit
      and a fluorescent moiety are linked to two imidazolium rings have been designed
      and prepared from 1,1'-bis(imidazolylmethyl)ferrocene. Their crystal structures
      revealed that these receptors are capable of incorporating anions such as PF(6)(
      ) and Br(-). Consequently, the anion binding studies were carried out using
      various techniques including electrochemistry (CV and OSWV), fluorescence, UV
      vis, and (1)H NMR spectroscopy. All the receptors showed a special
      electrochemical response to the F(-) anion with a remarkable cathodic shift of
      more than 260 mV and displayed a unique selectivity for F(-) and AcO(-) anions
      with fluorescence enhancement over various other anions of present interest (Cl(
      ), Br(-), I(-), HSO(4)(-), H(2)PO(4)(-)). In addition, for receptor , obvious
      absorption changes were observed when the H(2)PO(4)(-) anion was added while
      other anions (F(-), Cl(-), Br(-), I(-), AcO(-), HSO(4)(-)) showed only a minor
      influence on the UV-vis spectra. (1)H NMR titrations demonstrated that receptors
      and can bind anions through (C-H)(+)X(-) hydrogen bonds and showed strong
      affinity and high selectivity for the AcO(-) anion in acetonitrile.

PMID- 18615216
TI  - Spectroscopic, electrochemical and computational study of Pt-diimine-dithiolene
      complexes: rationalising the properties of solar cell dyes.
AB  - A series of [Pt(ii)(diimine)(dithiolate)] complexes of general formula [Pt{X,X'
      (CO(2)R)(2)-bpy}(mnt)] (where X = 3, 4 or 5; R = H or Et, bpy = 2,2'-bipyridyl
      and mnt = maleonitriledithiolate), have been spectroscopically, electrochemically
      and computationally characterised and compared with the precursors [Pt{X,X'
      (CO(2)R)(2)-bpy}Cl(2)] and X,X'-(CO(2)R)(2)-bpy. The study includes cyclic
      voltammetry, in situ EPR spectroelectrochemical studies of fluid solution and
      frozen solution samples, UV/Vis/NIR spectroelectrochemistry, hyrid DFT and TD-DFT
      calculations. The effect of changing the position of the bpy substituents from
      3,3' to 4,4' and 5,5' is discussed with reference to electronic changes seen
      within the different members of the family of molecules. The performance of the
      mnt complexes in dye-sensitised solar cells has been previously described and the
      superior performance of [Pt{3,3'-(CO(2)R)(2)-bpy}(mnt)] is now explained in terms
      of decreased electronic delocalisation through twisting of the bipyridyl ligand
      as supported by the EPR and computational results.

PMID- 18615217
TI  - Structure determination and characterization of two rare-earth molybdenum borate
      compounds: LnMoBO(6) (Ln = La, Ce).
AB  - The structural, optical, and electronic properties of two rare-earth molybdenum
      borate compounds, LnMoBO(6) (Ln = La, Ce), have been investigated by means of
      single-crystal X-ray diffraction, elemental analyses, and spectral measurements,
      as well as calculations of energy band structures, density of states, and optical
      response functions by the density functional method. The title compounds, which
      crystallize in monoclinic space group P2(1)/c, possess a similar network of
      interconnected [Ce(2)(MoO(4))(2)](2+) chains and [BO(2)](-) wavy chains. Novel 1D
      molybdenum oxide chains are contained in their three-dimensional (3D) networks.
      The calculated results of crystal energy band structure by the density functional
      theory (DFT) method show that the solid-state compound LaMoBO(6) is a
      semiconductor with indirect band gaps.

PMID- 18615218
TI  - Mixed amido/imido/guanidinato complexes of niobium: potential precursors for
      MOCVD of niobium nitride thin films.
AB  - Novel mixed amido/imido/guanidinato complexes of niobium are reported. The
      complexes were synthesized by insertion of two equivalents of di
      isopropylcarbodiimide (i-Pr-cdi) or bis-cyclohexylcarbodiimide (Cy-cdi)
      respectively, into the niobium-amido bonds of [Nb(NR(2))(3)(N-t-Bu)] (, R = Me; ,
      R = Et) starting out from [NbCl(3)(N-t-Bu)(py)(2)] and the respective LiNR(2)
      reagent (py = pyridine). Four representative examples of these mixed ligand
      amido/imido/guanidinato compounds were synthesized and were characterized by (1)H
      NMR, (13)C-NMR, (15)N-NMR, CHN-analysis, mass spectrometry and infra-red
      spectroscopy. The molecular structures of [Nb(NR(2)){eta(2)-(i-Pr
      N)(2)C(NR(2))}(2)(N-t-Bu)] (, R = Me; , R = Et) in the solid state were
      determined by single-crystal X-ray diffraction studies and are discussed together
      with the molecular structure of the starting compound [Nb(NMe(2))(3)(N-t-Bu)] ().
      The thermal properties of the new compounds depend on the substitution at the
      guanidinato ligand. Complexes of i-Pr-cdi are significantly more volatile than
      complexes of Cy-cdi as revealed by thermogravimetric analysis. Preliminary
      experiments using as a single-molecule source for metal-organic chemical vapour
      deposition (MOCVD) in the absence of ammonia indicate the formation of the
      stoichiometric, and surprisingly carbon-free, cubic niobium nitride phase.

PMID- 18615219
TI  - Structural, (197)Au Mossbauer and solid state (31)P CP/MAS NMR studies on bis
      (cis-bis(diphenylphosphino)ethylene) gold(I) complexes [Au(dppey)(2)]X for X =
      PF(6), I.
AB  - (197)Au Mossbauer spectra for the d(10) gold(i) phosphine complexes,
      [Au(dppey)(2)]X (X = PF(6), I; dppey = (cis-bis(diphenylphosphino)ethylene), and
      the single crystal X-ray structure and solid state (31)P CPMAS NMR spectrum of
      [Au(dppey)(2)]I are reported here. In [Au(dppey)(2)]I the AuP(4) coordination
      geometry is distorted from the approximately D(2) symmetry observed for the
      PF(6)(-) complex with Au-P bond lengths 2.380(2)-2.426(2) A and inter-ligand P-Au
      P angles 110.63(5)-137.71(8) degrees . Quadrupole splitting parameters derived
      from the Mossbauer spectra are consistent with the increased distortion of the
      AuP(4) coordination sphere with values of 1.22 and 1.46 mm s(-1) for the PF(6)(-)
      and I(-) complexes respectively. In the solid state (31)P CP MAS NMR spectrum of
      [Au(dppey)(2)]I, signals for each of the four crystallographically independent
      phosphorus nuclei are observed, with the magnitude of the (197)Au quadrupole
      coupling being sufficiently large to produce a collapse of (1)J(Au-P) splitting
      from quartets to doublets. The results highlight the important role played by the
      counter anion in the determination of the structural and spectroscopic properties
      of these sterically crowded d(10) complexes.

PMID- 18615220
TI  - Controlling the binding of dihydrogen using ruthenium complexes containing N-mono
      functionalised 1,4,7-triazacyclononane ligand systems.
AB  - Pendant arm macrocycles derived from 1,4,7-triazacyclononane were reacted with
      RuHCl(CO)(PPh(3))(3) and RuHCl(PPh(3))(3) to yield air-stable cationic ruthenium
      hydrides that were characterised by a variety of techniques, including X-ray
      crystallography. Protonation of the metal hydride complexes with a proton source
      yielded eta(2)-dihydrogen complexes. The lifetime of the dihydrogen ligand was
      effected by a judicious choice of ancillary ligands.

PMID- 18615221
TI  - Magnesium amido N-heterocyclic carbene complexes.
AB  - Magnesium dications bind strongly to a tridentate anionic dicarbene ligand L =
      [N{CH(2)CH(2)(CNCHCHNMes)}(2)] forming dinuclear and trinuclear Mg complexes with
      some particularly short Mg-C bonds. Treatment of the proligand H(4)LCl(3) with
      three equivalents of methyl magnesium chloride or benzyl magnesium chloride
      affords Mg(3)(HL)Cl(6) in high yield. A suspension of in thf was heated to 80
      degrees C for 2 h to afford Mg(2)(L)Cl(3), consistent with the loss of one
      equivalent of MgCl(2), and the deprotonation of the remaining acidic NH, lost as
      HCl gas. Treatment of Mg(3)(HL)Cl(6) with one equivalent of KC(8) results in
      deprotonation of the ligand amine NH to afford Mg(3)(L)Cl(5); treatment with a
      second equivalent forms the radical anion of the complex, K[Mg(3)(L)Cl(5)], which
      decomposes upon storage, precluding its structural characterisation. The acidic
      NH proton of the ligand in Mg(3)(HL)Cl(6) can also be removed by deprotonation
      with Li{N(SiMe(3))(2)}; additional equivalents of which also exchange the
      magnesium-bound chlorides for silylamido ligands, affording Mg(2)(L)Cl(2)N'' and
      Mg(2)(L)Cl(N'')(2), which have both been characterised by single-crystal X-ray
      diffraction studies.

PMID- 18615222
TI  - O(2) activation and hydrolysis of Salan rare-earth metal alkyl complexes.
AB  - Salan ligated yttrium alkyl complex , L(1)Y(CH(2)SiMe(3))(THF) (Salan = L(1): [2
      O-3,5-tBu(2)-C(6)H(2)CH(2)N(CH(3))CH(2)](2)), was exposed to an oxygen/nitrogen
      atmosphere to give a bimetallic alkoxide complex , [L(1)Y(mu-OCH(2)SiMe(3))](2).
      Whilst the lutetium counterparts (L(1)Lu(CH(2)SiMe(3))(THF)) and
      (L(2)Lu(CH(2)SiMe(3))(THF); L(2): [2-O-3-tBu-C(6)H(2)CH(2)N(CH(3))CH(2)](2)) were
      hydrolysed with moist nitrogen to afford mixed hydroxy/silyloxy complexes and
      ([L(1,2)Lu(mu-OSiMe(3))(mu-OH)LuL(1,2)]), respectively.

PMID- 18615223
TI  - Promotion of phosphaalkyne cyclooligomerisation by a Sb(v) to Sb(iii) redox
      process.
AB  - A high yield of the tetraphosphaladderene, anti
      tetraphosphatricyclo[4.2.0.0(2,5)]octa-3,7-diene, is obtained from reaction of
      the zirconocene 1,3-diphosphabicyclo[1.1.0]butane with Ph(2)SbCl(3) in THF or
      CH(2)Cl(2). Exploration of the reaction pathway using density functional theory
      suggests that an envelope-type adduct of Ph(2)SbCl and 1,3
      diphosphabicyclo[1.1.0]butane plays a pivotal role in the reaction. The
      zwitterionic character of this intermediate species allows it to act
      simultaneously as both an ene and an eneophile, and a symmetry-allowed
      bimolecular reaction leads to the tetraphosphaladderene species via a spirocyclic
      intermediate.

PMID- 18615224
TI  - The developmental origins of sarcopenia.

PMID- 18615226
TI  - Sarcopenia: diagnosis and treatment.

PMID- 18615227
TI  - Physical activity, dementia, and BPSD.

PMID- 18615228
TI  - Dietary intervention in older adults with early-stage Alzheimer dementia: early
      lessons learned.
AB  - In older adults, an adequate diet depends on their ability to procure and prepare
      food and eat independently or the availability of dietary assistance when needed.
      Inadequate food intake or increased nutritional requirements lead to poor
      nutritional status, which is considered a key determinant of morbidity, increased
      risk of infection, and mortality in elderly individuals. Weight loss among
      seniors also heralds increased morbidity and mortality. Dietary behaviour
      disorders affecting food consumption, nutrition status and maintenance of body
      weight are common in older adults, and have a substantial impact on nutritional
      status and quality of life among older adults with Alzheimer Dementia (AD). The
      Nutrition Intervention Study (NIS) is ongoing. It employs a quasi-experimental
      pre-post intervention design in physically-well, community-dwelling early stage
      AD patients aged 70 y or older. To date, 34 intervention group patients and 25
      control group participants have been recruited with their primary caregivers (CG)
      from 6 hospital-based memory and geriatric clinics in Montreal. The NIS uses
      clinical dietetics principles to develop and offer tailored dietary strategies to
      patients and their CG. This paper reports on the application of dietary
      intervention strategies in two intervention group participants; one was deemed
      successful while the other was considered unsuccessful. The report documents
      challenges encountered in assessing and counselling this clientele, and seeks to
      explain the outcome of intervention in these patients.

PMID- 18615225
TI  - Sarcopenia: its assessment, etiology, pathogenesis, consequences and future
      perspectives.
AB  - Sarcopenia is a loss of muscle protein mass and loss of muscle function. It
      occurs with increasing age, being a major component in the development of
      frailty. Current knowledge on its assessment, etiology, pathogenesis,
      consequences and future perspectives are reported in the present review. On-going
      and future clinical trials on sarcopenia may radically change our preventive and
      therapeutic approaches of mobility disability in older people.

PMID- 18615229
TI  - Target population for clinical trials on sarcopenia.
AB  - The term "sarcopenia" describes the progressive decline of muscle mass, strength
      and function occurring with aging. It is not considered a disease, but the direct
      consequence of the aging process on the skeletal muscle. Multiple demographic
      (e.g. gender, race), biological (e.g. inflammatory status) and clinical (e.g.
      diabetes, metabolic syndrome, congestive heart failure, medications) factors are
      able to influence (positively or negatively) the skeletal muscle quality and
      quantity. The extreme paucity of clinical trials on sarcopenia in literature is
      mainly due to difficulties in designing studies able to isolate the aging process
      from its multiple and interconnected consequences. In the present review, we
      present the major factors to consider as potential sources of biased results when
      evaluating potential candidates for clinical trials on sarcopenia. The
      development of clinical trials exploring the nature of the sarcopenia process is
      urgent, but several controversial issues on this hallmark of aging still need
      clarification.

PMID- 18615230
TI  - Ace inhibitors as a therapy for sarcopenia - evidence and possible mechanisms.

PMID- 18615231
TI  - The danger of weight loss in the elderly.
AB  - Aging is generally accompanied by weight loss made up of both fat mass and fat
      free mass. As more people, including elderly, are overweight or obese, weight
      loss is recommended to improve health. Health risks are decreased in overweight
      children and adults by dieting and exercise, but the health benefits of weight
      loss in elderly, particularly by calorie restriction, are uncertain. Rapid
      unintentional weight loss in elderly is usually indicative of underlying disease
      and accelerates the muscle loss which normally occurs with aging. Intentional
      weight loss, even when excess fat mass is targeted also includes accelerated
      muscle loss which has been shown in older persons to correlate negatively with
      functional capacity for independent living. Sarcopenic obesity, the coexistence
      of diminished lean mass and increased fat mass, characterizes a population
      particularly at risk for functional impairment since both sarcopenia (relative
      deficiency of skeletal muscle mass and strength) and obesity have been shown to
      predict disability. However, indices of overweight and obesity such as body mass
      index (BMI) do not correlate as strongly with adverse health outcomes such as
      cardiovascular disease in elderly as compared to younger individuals. Further,
      weight loss and low BMI in older persons are associated with mortality in some
      studies. On the other hand, studies have shown improvement in risk factors after
      weight loss in overweight/obese elderly. The recent focus on pro-inflammatory
      factors related to adiposity suggest that fat loss could ameliorate some
      catabolic conditions of aging since some cytokines may directly impact muscle
      protein synthesis and breakdown. Simply decreasing weight may also ease
      mechanical burden on weak joints and muscle, thus improving mobility. However,
      until a strategy is proven whereby further loss of muscle mass can be prevented,
      weight loss by caloric restriction in individuals with sarcopenic obesity should
      likely be avoided.

PMID- 18615232
TI  - Lower extremity muscle mass predicts functional performance in mobility-limited
      elders.
AB  - OBJECTIVES: This study examined the influence of lower extremity body composition
      and muscle strength on the severity of mobility-disability in community-dwelling
      older adults. METHODS: Fifty-seven older males and females (age 74.2 +/- 7 yrs;
      BMI 28.9 +/- 6 kg/m2) underwent an objective assessment of lower extremity
      functional performance, the Short Physical Performance Battery test (SPPB).
      Participants were subsequently classified as having moderate (SPPB score 7: n =
      38) or severe mobility impairments (SPPB score <or= 7: n = 19). Body composition
      was assessed using dual-energy X-ray absorptiometry and provided measures of bone
      mineral density (BMD), total leg lean mass (TLM) and total body fat. Maximal hip
      extensor muscle strength was estimated using the bilateral leg press exercise.
      Multiple logistic regression analysis was utilized to identify the significant
      independent variables that predicted the level of mobility-disability. RESULTS:
      TLM was a strong independent predictor of the level of functional impairment,
      after accounting for chronic medical conditions, BMD, body fat, body weight and
      habitual physical activity. In a separate predictive model, reduced muscle
      strength was also a significant predictor of severe functional impairment. The
      severity of mobility-disability was not influenced by gender (p = 0.71). A strong
      association was elicited between TLM and muscle strength (r = 0.78, p < 0.01).
      CONCLUSIONS: These data suggest that lower extremity muscle mass is an important
      determinant of physical performance among functionally-limited elders. Such
      findings may have important implications for the design of suitable strategies to
      maintain independence in older adults with compromised physical functioning.
      Additional studies are warranted to assess the efficacy of lifestyle, exercise or
      therapeutic interventions for increasing lean body mass in this population.

PMID- 18615234
TI  - Microelectrode findings and topographic reorganisation of kinaesthetic cells
      after gamma knife thalamotomy.
AB  - A 64-year-old woman with Parkinson is disease had a severe resting tremor that
      was not completely relieved by right-sided gamma knife thalamotomy (GKT). We
      performed bilateral staged thalamic deep brain stimulation (DBS) and compared the
      right and left ventral intermediate nucleus (Vim) of the thalamus including the
      frequency of single units recorded with microelectrodes, and also the
      somatotopical distribution of kinaesthetic cells (Ki). The average frequency of
      units for the presumed left Vim exceeded that of the right (22.6 +/- 19.2 Hz vs.
      14.3 +/- 8.8 Hz). Regarding the somatotopic distribution of Ki, the receptive
      field for the leg, which is usually situated in the dorsolateral Vim, was more
      widely scattered in the right Vim than the non-lesioned left side. Our findings
      raise the possibility that the specific properties of the neurons changed due to
      partial coagulation by GKT within both the coagulated and the surrounding
      thalamic lesions.

PMID- 18615233
TI  - Bacterial diversity of a consortium degrading high-molecular-weight polycyclic
      aromatic hydrocarbons in a two-liquid phase biosystem.
AB  - High-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs) are
      pollutants that persist in the environment due to their low solubility in water
      and their sequestration by soil and sediments. Although several PAH-degrading
      bacterial species have been isolated, it is not expected that a single isolate
      would exhibit the ability to degrade completely all PAHs. A consortium composed
      of different microorganisms can better achieve this. Two-liquid phase (TLP)
      culture systems have been developed to increase the bioavailability of poorly
      soluble substrates for uptake and biodegradation by microorganisms. By combining
      a silicone oil-water TLP system with a microbial consortium capable of degrading
      HMW PAHs, we previously developed a highly efficient PAH-degrading system. In
      this report, we characterized the bacterial diversity of the consortium with a
      combination of culture-dependent and culture-independent methods. Polymerase
      chain reaction (PCR) of part of the 16S ribosomal RNA gene (rDNA) sequences
      combined with denaturing gradient gel electrophoresis was used to monitor the
      bacterial population changes during PAH degradation of the consortium when
      pyrene, chrysene, and benzo[a]pyrene were provided together or separately in the
      TLP cultures. No substantial changes in bacterial profiles occurred during
      biodegradation of pyrene and chrysene in these cultures. However, the addition of
      the low-molecular-weight PAHs phenanthrene or naphthalene in the system favored
      one bacterial species related to Sphingobium yanoikuyae. Eleven bacterial strains
      were isolated from the consortium but, interestingly, only one-IAFILS9 affiliated
      to Novosphingobium pentaromativorans-was capable of growing on pyrene and
      chrysene as sole source of carbon. A 16S rDNA library was derived from the
      consortium to identify noncultured bacteria. Among 86 clones screened, 20 were
      affiliated to different bacterial species-genera. Only three strains were
      represented in the screened clones. Eighty-five percent of clones and strains
      were affiliated to Alphaproteobacteria and Betaproteobacteria; among them,
      several were affiliated to bacterial species known for their PAH degradation
      activities such as those belonging to the Sphingomonadaceae. Finally, three genes
      involved in the degradation of aromatic molecules were detected in the consortium
      and two in IAFILS9. This study provides information on the bacterial composition
      of a HWM PAH-degrading consortium and its dynamics in a TLP biosystem during PAH
      degradation.

PMID- 18615235
TI  - Localization of stilbene synthase in Vitis vinifera L. during berry development.
AB  - The localization of stilbene synthase (STS) (EC 2.3.1.95) in grape berry (Vitis
      vinifera L.) was investigated during fruit development. The berries were
      collected at 2, 4, 7, 11, and 15 weeks postflowering from the cultivar Nebbiolo
      during the 2005 and 2006 growing seasons. High-performance liquid chromatography
      analysis showed that berries accumulated cis- and trans-isomers of resveratrol
      mainly in the exocarp throughout fruit development. Immunodetection of STS
      protein was performed on berry extracts and sections with an antibody
      specifically developed against recombinant grape STS1. In agreement with
      resveratrol presence, STS was found in berry exocarp tissues during all stages of
      fruit development. The labeled epidermal cells were few and were randomly
      distributed, whereas nearly all the outer hypodermis cells were STS-positive. The
      STS signal decreased gradually from exocarp to mesocarp, where the protein was
      detected only occasionally. At the subcellular level, STS was found predominantly
      within vesicles (of varying size), along the plasma membrane and in the cell
      wall, suggesting protein secretion in the apoplast compartment. Despite the
      differences in fruit size and structure, the STS localization was the same before
      and after veraison, the relatively short developmental period during which the
      firm green berries begin to soften and change color. Nevertheless, the amount of
      protein detected in both exocarp and mesocarp decreased significantly in ripe
      berries, in agreement with the lower resveratrol content measured in the same
      tissues. The location of STS in exocarp cell wall is consistent with its role in
      synthesizing defense compounds and supports the hypothesis that a differential
      localization of phenylpropanoid biosynthetic machinery regulates the deposition
      of specific secondary products at different action sites within cells.

PMID- 18615236
TI  - Are histones, tubulin, and actin derived from a common ancestral protein?
AB  - Histones and the cytoskeletal components tubulin and actin all act as thermal
      ratchets, using the energy present in Brownian motion to do work. All three also
      bind to nucleotides. Here we suggest that histones, tubulin, and actin derive
      from a common ancestral protein. There is some sequence similarity between
      histone 2A and the bacterial tubulin homologue FtsZ. Histones and actin also
      share some sequence similarity in the nucleotides and at phosphate-binding sites.
      Thus, actin and tubulin may also be related, although this is not obvious from
      sequence analysis. Indeed, actin and tubulin are closely functionally related and
      cooperate in many cellular processes. Interestingly, recent advances in
      nanotechnology suggest that thermal ratchets may be able to impart lifelike
      properties; thus, the evolution of the ancestral histone, tubulin, and actin
      thermal ratchet may have been crucial in the development of complexity in living
      organisms.

PMID- 18615237
TI  - Transcriptional activity and distribution of splicing machinery elements during
      Hyacinthus orientalis pollen tube growth.
AB  - The localization of newly formed transcripts and molecules participating in pre
      mRNA splicing, i.e., small nuclear ribonucleoproteins (snRNPs) and SC35 protein,
      in growing pollen tubes of Hyacinthus orientalis L. were analyzed in vitro and in
      vivo. The results indicated that the restart of RNA synthesis occurred first in
      the vegetative and then in the generative nucleus of both in vitro and in vivo
      growing pollen tubes. Changes in RNA synthesis were accompanied by the
      redistribution of splicing machinery elements in both vegetative and generative
      nuclei of the growing pollen tube. At stages of pollen tube growth when the
      vegetative and generative nuclei were transcriptionally active, clear differences
      in the distribution pattern of the splicing system components were observed in
      both pollen nuclei. While both small nuclear RNA with a trimethylguanosine cap on
      the 5' end and SC35 protein were diffusely distributed in the nucleoplasm in the
      vegetative nucleus, the studied antigens were only present in the areas between
      condensed chromatin in the generative nucleus. When the transcriptional activity
      of both pollen nuclei could no longer be observed at later stages of pollen tube
      growth, snRNPs and SC35 protein were still present in the vegetative nuclei but
      not in the generative nuclei. We, therefore, investigated potential differences
      in the spatial organization of splicing system elements during pollen tube
      growth. They clearly reflect differences in gene expression patterns in the
      vegetative and the generative cells, which may be determined by the different
      biological roles of angiosperm male gametophyte cells.

PMID- 18615238
TI  - Cytological investigation of Haplopappus gracilis (Nutt.) Gray: 5-methylcytosine
      rich regions, fluorochrome banding and chromatin sensitivity to DNase I
      digestion.
AB  - Haplopappus gracilis (Nutt.) Gray, one of the five known higher plants with a
      chromosome number of 2n = 4, was studied from a cytological point of view. The
      chromosome complement of this species was characterized by means of automated
      karyotype analysis. Moreover, the DNA methylation pattern and fluorochrome
      banding were determined and compared with cytological data present in the
      literature. DNA methylation distribution along metaphase chromosomes involved all
      chromosome territories evidenced by C-banding. Other methylated bands correlated
      positively with aceto-orcein-positive heterochromatic portions and/or with late
      replicating bands and/or fluorochrome bands. Some methylated bands showed
      differences between homologous chromosomes. These bands belonged partly to
      certain heterochromatic domains and partly to intercalary sites not defined by
      other standard banding techniques. Differences between the homologues were also
      indicated by our DNA content data obtained after DNase I digestion.

PMID- 18615239
TI  - INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese.
AB  - The single nucleotide polymorphism (SNP) rs7566605 in the upstream region of the
      insulin-induced gene 2 (INSIG2) is associated with the obesity phenotype in many
      Caucasian populations. In Japanese, this association with the obesity phenotype
      is not clear. To investigate the relationship between rs7566605 and obesity in
      Japanese, we genotyped rs7566605 from severely obese subjects [n = 908, body mass
      index (BMI) > or = 30 kg/m2] and normal-weight control subjects (n = 1495, BMI <
      25 kg/m2). A case-control association analysis revealed that rs7566605 was
      significantly associated with obesity in Japanese. The P value in the minor
      allele recessive mode was 0.00020, and the odds ratio (OR) adjusted for gender
      and age was 1.61 [95% confidential interval (CI) = 1.24-2.09]. Obesity-associated
      phenotypes, which included the level of BMI, plasma glucose, hemoglobin A1c,
      total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and
      blood pressure, were not associated with the rs7566605 genotype. Thus, rs7566605
      in the upstream region of the INSIG2 gene was found to be associated with
      obesity, i.e., severe obesity, in Japanese.

PMID- 18615240
TI  - Blood loss and short-term outcome of infants undergoing brain tumour removal.
AB  - OBJECTIVE: To evaluate perioperative management, early outcomes and
      hemocoagulative disorders in infants up to 1 year old, undergoing neurosurgery
      for brain tumors removal. DESIGN: Retrospective evaluation of prospectively
      collected data regarding all infants aged <1 year admitted to PICU from 1994 to
      2004, following intracranial mass removal. INTERVENTIONS: none. SETTING:
      University Hospital PICU in a tertiary neurosurgical referral centre. PATIENTS
      AND PARTICIPANTS: All eligible infants were enrolled in the study. Population was
      constituted by 43 infants and subdivided in two groups, according to their intra
      operative blood loss. Babies having blood loss exceeding the preoperative
      estimated volemia were classified in group A; the remaining babies were included
      in group B. RESULTS: Intraoperative transfusions, PICU length of stay, need for
      post-operative mechanical ventilation and cardiovascular support were all
      significantly higher in group A than in group B. No early postoperative mortality
      occurred. ROC analysis and multiple logistic regression showed the age as the
      only variable independently associated with blood loss exceeding preoperative
      volemia (cut-off 60.3 days; OR = 0.11, CI 0.02-0.55, sensitivity 82.4%;
      specificity 67%). Postoperatively, platelet count, prothrombin activity and
      fibrinogen resulted significantly depressed in group A, representing a dilutional
      coagulopathy. A marked dispersion of aPTT values was recorded in group B, where
      most infants exhibit aPTT shortening, suggesting a hypercoagulability status.
      Three episodes of clinical disseminated intravascular coagulation (DIC) were
      registered in group B. CONCLUSIONS: We illustrated the relationships between
      intraoperative blood loss, transfusions and haemostatic impairment in babies
      following brain tumor removal. Youngest infants had the higher risk to experience
      hemocoagulative disorders. These infants showed significantly higher impact on
      the global PICU burden of care, as represented by the need of mechanical
      ventilation, cardiovascular support and PICU length of stay.

PMID- 18615241
TI  - Superior keratoconus with hydrops.
AB  - Superior keratoconus is a rare form of keratoconus, in which the corneal apex is
      atypically superior. We report a 32-year-old man who presented with corneal
      hydrops in his right eye. Ophthalmic examination revealed corneal edema with
      Descemet's break involving the superior part of his right cornea. Superior
      steepening in the left cornea demonstrated by corneal topography was consistent
      with subclinical keratoconus.

PMID- 18615242
TI  - Production of human T-cell clones.
AB  - The study of monoclonal human T-cell populations has had a fundamental impact on
      our current knowledge of the function, specificity, and mechanisms of activation
      of these cells. The frequency of antigen-specific T cells in peripheral blood is
      low, necessitating several enrichment steps prior to the isolation of individual
      clones. Two different methods of limiting dilution cloning are described in this
      chapter, the choice of which depends on the availability of starting materials.
      After isolation, T-cell clones are expanded and then tested for specificity and
      cryopreserved, both of which are described.Recently, time-saving variations to
      the above methods have emerged. However, they require the use of sophisticated
      equipment and reagents, making them less economical than the established
      techniques.

PMID- 18615243
TI  - Mapping of human T-cell epitopes of allergens.
AB  - Allergens are characterized by their ability to be bound by gE. The Swiss-Prot
      protein database currently lists a partial or complete amino acid sequence of in
      excess of about 350 allergens. It is not clear how allergens participate in the
      process of allergic sensitization, the generation of specific T-helper type 2
      (Th2) lymphocytes, which play a crucial role in stimulating B lymphocytes to
      produce allergen-specific IgE.T-helper (Th) cells play a key role in the
      regulation of immune responses. The recognition of antigen by T cells is complex
      and it can trigger qualitatively differential signaling. Therefore, it is
      conceivable that epitopes or antigenic determinants recognized by Th cells may
      influence the quality of immune response. The aim of this chapter is to describe
      the way in which T-cell epitopes can be identified (mapped). This is particularly
      important because knowledge of the precise T-cell epitopes of allergens can give
      important information on the pathogenesis of allergy and can help to develop
      better preparations for the diagnostics and/or immunotherapy of allergy.

PMID- 18615244
TI  - Determining MHC restriction of T-cell responses.
AB  - T-cell receptors (TcR) recognize short linear peptides (9-15 amino acid long),
      which have been processed by an 'antigen-presenting cell' and complexed to
      products of the major histocompatibility complex (MHC). Peptides of the
      appropriate shape and charge are able to bind within the groove of the MHC
      molecule and it is this complex which is recognized by the TcR. The MHC molecules
      are highly polymorphic, but each individual will only express one maternal and
      one paternal allele of HLA Class 1 molecule A, B, and C and HLA Class II DR, DP,
      and DQ. As a result of TcR specificity and MHC restriction, a clone of T cells
      will bear a specific receptor which has a very limited repertoire of targets
      (peptide-MHC complexes). When sufficient numbers of TcR are engaged on a T-cell
      surface, a cascade of signal transduction events is initiated which results in
      cellular activation. When investigating the immune response, it may be
      advantageous to be able to identify which MHC molecules bind a particular peptide
      well and give rise to a vigorous T-cell response. Such information may be useful
      in generating effective vaccines. In this chapter, we provide examples of Epstein
      Barr virus-transformed lymphoid cell lines and fibroblast cell lines to determine
      MHC restriction elements.

PMID- 18615245
TI  - Short-term culture of CD8 cells and intracellular cytokine staining.
AB  - CD8 T cells play an important role in the regulation of allergic disease. Human
      and murine CD8 T cells have been shown to be capable of differentiating into
      distinct subsets defined by cytokine profiles analogous to the Th1 and Th2
      subsets and termed T cytotoxic 1 (Tc1, IFN-gamma producing) and 2 (Tc2, IL-4
      producing). Effector cell phenotype can be analyzed in vitro on a single cell
      basis using intracellular cytokine staining and flow cytometry or analysis of
      other phenotypic markers. Human PBMC usually contain only very low percentages of
      effector cells which produce relatively high levels of cytokines required for
      this kind of analysis. It is therefore necessary to activate the T cells to
      induce rapid accumulation of cytoplasmic cytokines before analysis. This makes it
      difficult to analyze the antigen specificity of responding T cells but will
      indicate the type 1/type 2 bias of the population, reflecting previous exposures
      to antigen. In this chapter, we provide protocols for the generation of polarized
      populations of CD8 T effector cells using polyclonal stimulation and for their
      subsequent analysis by intracellular cytokine staining.

PMID- 18615246
TI  - Isolation, flow cytometric analysis, and suppression assay of CD4+ CD25+ T
      regulatory cells.
AB  - Allergy and asthma are characterized by airway hyperresponsiveness and chronic
      mucosal inflammation mediated by CD4+ Th2 lymphocytes and their cytokines. It is
      unclear why allergic individuals make a Th2-type T-cell response whereas other
      (non-allergic) individuals do not. Recently, attention has focused on regulatory
      mechanisms, such as T-regulatory cells, preventing IgE responses to allergens in
      nonatopic individuals. Regulatory CD4+CD25+ T cells have been described in both
      mice and humans. The suppressive phenotype of these cells has been associated
      with the expression of the forkhead transcription factor, Foxp3. It has been
      suggested that allergic disease may arise from an inappropriate balance between
      allergen activation of regulatory CD4+CD25+ T cells and effector Th2 cells or
      from the impairment in the suppressive activity of these so-called T-regulatory
      cells. The isolation of these T-regulatory cells is described in order to further
      our understanding of the role of these cells in allergic disease and asthma and
      allow us to design novel therapies.

PMID- 18615247
TI  - Monocyte-derived dendritic cells as antigen-presenting cells in T-cell
      proliferation and cytokine production.
AB  - Dendritic cells (DC) are widely considered to be the major antigen-presenting
      cell (APC) type in immune responses. These cells are obtained from adherent cells
      or are purified CD14(+) monocytes from peripheral blood mononuclear cells (PBMC)
      by in vitro stimulation with granulocyte, macrophage-colony-stimulating factor
      (GM-CSF) plus interleukin (IL)-4. They express high levels of MHC class II and
      costimulatory molecules, internalize Ag rapidly via Fc receptors and mannose
      receptors, and, by macropinocytosis, produce large amounts of IL-12 on CD40
      ligation, and are potent in presenting soluble Ag and in stimulating allogeneic
      mixed-leukocyte reactions. To study primary T-cell responses and cytokine
      production in allergy patients, we have developed an in vitro system by using
      highly purified T cells as responder cells and monocyte-derived DC (MDC) as the
      APC. MDC provide a convenient and potent APC source for T-cell response studies.

PMID- 18615248
TI  - [Confluent indurated facial nodules and pustules in a 55-year-old man].

PMID- 18615249
TI  - [Pulmonary mass suspected as malignant tumour. Thoracic wall abscess and fistula
      after pulmonary segmental resection].
AB  - A 31-year-old patient presented with chronic cough and thoracic pain. A pulmonary
      mass was seen on chest x-ray, and pulmonary segmental resection was done.
      Histopathologically, a pulmonary abscess cavity due to actinomycosis was found.
      Three months later, recurrence of actinomycosis at the thoracic wall was
      observed. Antibiotic therapy with penicillin was administered. Five months later,
      with the patient receiving continued antibiotic therapy, a thoracic wall abscess
      and fistula was diagnosed. Four weeks after abscess drainage and repeat
      intravenous antibiotic therapy, the patient was symptom-free and had remained
      symptom-free at 10 months of follow-up.

PMID- 18615250
TI  - Response to hypercapnic challenge is associated with successful weaning from
      prolonged mechanical ventilation due to brain stem lesions.
AB  - OBJECTIVE: We propose that higher airway occlusion pressure (P0.1) responses to
      hypercapnic challenge (HC) indicate less severe injury. The study aim was to
      determine whether P0.1 responses to HC were associated with successful weaning
      after prolonged mechanical ventilation (PMV) in patients with brainstem lesions
      and to determine a reference value for clinical use. DESIGN AND SETTING: Forty
      two patients with brainstem lesions on PMV were recruited. Breathing parameters
      and P0.1 were measured before HC. Three-minute HC challenges with increasing
      CO(2) concentrations were initiated and P0.1, respiratory rate, minute
      ventilation (V (e)), tidal volume (V (t)) and end tidal CO(2) were measured.
      MEASUREMENTS AND RESULTS: Patients were classified into high (group I) and low
      (group II) response groups on the basis of P0.1 responses to HC. Increases in V
      (e) and V (t) after HC were significantly greater in group I patients (12.22 +/-
      8.22 vs. 3.08 +/- 4.84 L/min, P < 0.001 and 399.11 +/- 278.18 vs. 110.54 +/-
      18.275 ml, P < 0.001). P0.1 levels were significantly higher in group I compared
      to group II before HC (2.69 +/- 1.81 vs. 1.28 +/- 1.04 cmH(2)O, P = 0.003). The
      increase in P0.1 following HC was significantly greater in group I compared to
      group II patients (11.05 +/- 4.06 vs. 2.90 +/- 2.53 cmH(2)O, P < 0.001). Weaning
      success was significantly higher in group I compared to group II patients (72.2%
      vs. 33.3%, P = 0.02). A P0.1 increase of >6 cmH(2)O following HC was
      significantly associated with successful weaning. CONCLUSIONS: Assessing the P.01
      response to serial increases in the level of HC may be a safe means to ascertain
      whether patients with brainstem lesions are ready for ventilator weaning.

PMID- 18615251
TI  - Phase 0 clinical trials in oncology: a paradigm shift for early drug development?
AB  - PURPOSE: To review the potential impact of Phase 0 trials conducted under the
      United States Food and Drug Administration (FDA) exploratory IND guidance on
      oncology drug development. METHODS: The FDA's exploratory IND guidance document
      is examined in detail and its practical application to specific first-in-human
      proof of concept clinical studies called Phase 0 trials is discussed. RESULTS:
      Phase 0 trials represent a novel strategy for accelerating the development of the
      next generation of anticancer treatments. Phase 0 studies are conducted prior to
      conventional toxicity-defined dose-escalation studies and these trials do not
      explore maximum toxicity levels and by definition are devoid of any therapeutic
      or diagnostic intent. They require less extensive formulation and non-clinical
      toxicity testing than conventional first-in-human Phase I trials. This pathway
      may be valuable in reducing the time and resources required to initiate clinical
      testing and it may also be useful in guiding the later stages of drug
      development. Alternatively, the early termination of a less than promising lead
      compounds could help in selecting the best agents for later clinical development.
      Possible disadvantages include the ethical challenge of testing non-therapeutic
      drug regimens in cancer patients and the need to conduct standard dose-escalation
      Phase I studies later in development. CONCLUSIONS: The potential of this novel
      pathway to accelerate drug development makes it worthy of further exploration,
      and National Cancer Institute has recently completed a Phase 0 trial
      demonstrating its applicability to targeted anticancer agents.

PMID- 18615252
TI  - Lipofibromatous hamartoma of the median nerve in patients with macrodactyly:
      diagnosis and treatment of a rare disease causing carpal tunnel syndrome.
AB  - Lipofibromatous hamartoma is a very rare benign peripheral nerve tumour. It is
      mostly encountered in the proximal extremities of young adults, involving the
      median nerve in the majority of cases. We present two patients with macrodactyly
      and carpal tunnel syndrome caused by lipofibromatous hamartoma of the median
      nerve and discuss diagnosis and treatment of the disease. A 10-year-old girl with
      a congenital progressive macrodactyly of her right index finger presented with a
      slowly growing mass in her right palm and pain and numbness, along with motor and
      sensory deficits in the median nerve distribution. Treatment consisted of carpal
      tunnel release, epineurolysis and partial excision of the fibrofatty tissue. The
      second patient, a 25-year-old man presented with a swelling in his left palm and
      findings compatible with carpal tunnel syndrome. Intraoperatively, the lesion
      presented as sausage-shaped enlargement of the median nerve by fibrofatty tissue.
      After carpal tunnel release, a partial excision of the mass with epineurolysis
      was performed. In both patients, histology showed nerve bundles separated by
      abundant fibrofatty tissue. In the girl, a proliferation of dysplastic
      perineurial cells could be observed. The suspected diagnosis for patients with
      macrodactyly and clinical signs of carpal tunnel syndrome should be
      lipofibromatous hamartoma. A carefully taken history, physical examination, X
      ray, and MRI are important for its correct diagnosis. The surgical management
      remains controversial. Treatment should include decompression of the median nerve
      at points of compression, partial excision of the fibrofatty tissue, and
      debulking of soft tissue. In some cases, an epineurolysis can be additionally
      performed.

PMID- 18615253
TI  - Association between tumor necrosis factor-alpha gene promoter polymorphism at
      position -308 and acne in Turkish patients.
AB  - Acne is a multifactorial, chronic inflammatory disease of pilosebaceous unit in
      which cytokines have been implicated in the pathogenesis. Although it is thought
      to be an inherited disease, there are limited data supporting the relevant
      genetic elements. Tumor necrosis factor-alpha (TNF-alpha) is one of the
      proinflammatory cytokines involved in the acne pathogenesis. Several single
      nucleotide polymorphisms (SNPs) have been identified in the human TNF-alpha gene
      promoter. The polymorphism at position -308, which involves substituting guanine
      (G) for adenine (A) (TNFA-308 G/A) has been linked to increased susceptibility to
      several chronic inflammatory diseases. The aim of this study was to determine the
      TNFA-308 G/A polymorphism in acne and to examine whether there is a relationship
      between this polymorphism and disease susceptibility. Exactly, 113 patients with
      acne and 114 healthy control subjects were included in the study. Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used
      for analysis of the TNFA-308 G/A polymorphism. We found that the frequency of the
      TNFA-308 GA genotype was statistically significantly increased in patients
      compared with healthy controls (P < 0.001). There was no association between TNFA
      genotypes and severity of acne (P > 0.05). There was also no significant
      difference between male and female patients. Our results suggest that TNFA-308
      G/A polymorphism may contribute to a predisposition to acne in Turkish
      population.

PMID- 18615254
TI  - Density and proportions of the epidermal T cell population in human sun-exposed
      skin differ from those in sun-protected skin: preliminary immunohistochemical
      study.
AB  - Epidermal T cells, which are found in clinically normal human skin, show
      topographic differences in density and proportions; however, the mechanisms and
      the biological consequences of such differences are still unknown. In a previous
      work, we showed that epidermal T cells are altered in number and composition
      after a single exposure to solar-simulated radiation (SSR). The purposes of the
      present investigation were, first, to compare the density of epidermal T cells
      and the proportion of T cell subpopulations in habitually sun-exposed versus sun
      protected sites; second, to determine the effects of repetitive exposures to SSR
      on the latter cell populations. Biopsies from habitually sun-exposed, sun
      protected and solar-simulated-exposed skin of 28 healthy volunteers were taken
      and immunohistochemistry was performed on cryostat sections. Compared with sun
      protected sites, epidermal CD3(+) T cell numbers of habitually sun-exposed sites
      were significantly lower. Double staining showed that the number of CD3(+)CD8(+)
      T cells was significantly lower in sun-exposed than in sun-protected skin,
      whereas the numbers of CD3(+)CD4(+) T cells were similar in both sites.
      Therefore, the CD4/CD8 ratio was markedly higher in sun-exposed compared to sun
      protected sites. Moreover, repeated exposures of sun-protected skin to SSR
      induced a significant reduction in number of epidermal CD3(+) T cells. The mean
      number of epidermal CD3(+)CD8(+) double stained cells significantly decreased
      after such exposures, while the epidermal CD3(+)CD4(+) T cell subpopulation was
      not significantly changed. In conclusion, both chronically sun-exposed skin and
      repeatedly SSR-exposed skin show a decrease in density of epidermal CD3(+) and
      CD3(+)CD8(+) T cells. We hypothesize that such sun-induced changes may weaken the
      immunosurveillance capacity of the skin and therefore increase the occurrence of
      skin cancer.

PMID- 18615256
TI  - Computational identification of transcription frameworks of early committed
      spermatogenic cells.
AB  - It is known that transcription factors (TFs) work in cooperation with each other
      to govern gene expression and thus single TF studies may not always reflect the
      underlying biology. Using microarray data obtained from two independent studies
      of the first wave of spermatogenesis, we tested the hypothesis that co-expressed
      spermatogenic genes in cells committed to differentiation are regulated by a set
      of distinct combinations of TF modules. A computational approach was designed to
      identify over-represented module combinations in the promoter regions of genes
      associated with transcripts that either increase or decrease in abundance between
      the first two major spermatogenic cell types: spermatogonia and spermatocytes. We
      identified five TFs constituting four module combinations that were correlated
      with expression and repression of similarly regulated genes. These modules were
      biologically assessed in the context that they represent the key transcriptional
      mediators in the developmental transition from the spermatogonia to spermatocyte.

PMID- 18615255
TI  - Pilot sequencing of onion genomic DNA reveals fragments of transposable elements,
      low gene densities, and significant gene enrichment after methyl filtration.
AB  - Sequencing of the onion (Allium cepa) genome is challenging because it has one of
      the largest nuclear genomes among cultivated plants. We undertook pilot
      sequencing of onion genomic DNA to estimate gene densities and investigate the
      nature and distribution of repetitive DNAs. Complete sequences from two onion
      BACs were AT rich (64.8%) and revealed long tracts of degenerated retroviral
      elements and transposons, similar to other larger plant genomes. Random BACs were
      end sequenced and only 3 of 460 ends showed significant (e < -25) non-organellar
      hits to the protein databases. The BAC-end sequences were AT rich (63.4%),
      similar to the completely sequenced BACs. A total of 499,997 bp of onion genomic
      DNA yielded an estimated mean density of one gene per 168 kb, among the lowest
      reported to date. Methyl filtration was highly effective relative to random
      shotgun reads in reducing frequencies of anonymous sequences from 82 to 55% and
      increasing non-organellar protein hits from 4 to 42%. Our results revealed no
      evidence for gene-dense regions and indicated that sequencing of methyl-filtered
      genomic fragments should be an efficient approach to reveal genic sequences in
      the onion genome.

PMID- 18615258
TI  - Percutaneous pedicle screws significantly decrease muscle damage and operative
      time: surgical technique makes a difference!

PMID- 18615259
TI  - The labor supply of registered nurses in Finland: the effect of wages and working
      conditions.
AB  - Many countries report, to varying degrees, of suffering from a shortage of
      nurses. We examined both pecuniary and non-pecuniary factors that may be
      associated with nurses' labor supply. We approximated a classical labor supply
      model and calculated the wage elasticities of hours of work and participation.
      Even though the wage elasticity was quite small, the effect on the hours supplied
      was significant. However, wages alone may not sufficiently increase the labor
      supply from the current stock of nurses; other elements, such as contractual
      conditions, seem to play an important role as well.

PMID- 18615257
TI  - Dopamine, kidney, and hypertension: studies in dopamine receptor knockout mice.
AB  - Dopamine is important in the pathogenesis of hypertension because of
      abnormalities in receptor-mediated regulation of renal sodium transport. Dopamine
      receptors are classified into D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3),
      D(4)) subtypes, all of which are expressed in the kidney. Mice deficient in
      specific dopamine receptors have been generated to provide holistic assessment on
      the varying physiological roles of each receptor subtype. This review examines
      recent studies on these mutant mouse models and evaluates the impact of
      individual dopamine receptor subtypes on blood pressure regulation.

PMID- 18615260
TI  - Lower extremity edema and pulmonary hypertension in morbidly obese patients with
      obstructive sleep apnea.
AB  - INTRODUCTION: In 70 consecutive male patients with obstructive sleep apnea (OSA)
      diagnosed at the Northport VA Medical Center Sleep Disorders Center, we have
      characterized the association between obesity, OSA, and pulmonary hypertension
      (PH). MATERIALS AND METHODS: By including anthropometric, pulmonary function, and
      sleep study parameters in a multivariate logistic regression model, we found that
      a BMI of >40 kg/m(2) and the minimum oxygen saturation in non-rapid eye movement
      (NREM) sleep predicted the presence of pretibial edema in this sleep apnea
      population. We then characterized the hemodynamics of those OSA patients that had
      lower extremity edema. Twenty-nine of the 70 consecutive patients with sleep
      apnea (41%) had pretibial edema, and right heart catheterization data was
      obtained for 28 (97%) of these patients. RESULTS AND DISCUSSION: Ninety-three
      percent (26/28) of the patients had right heart failure (mean RAP > 5 mm Hg; RAP
      range = 0-32 mmHg) and PH (PA mean >or= 20 mm Hg) was present in 86% (24/28.) The
      OSA patients with lower extremity edema had an increased cardiac output (7.0 +
      1.4 l/min) with a normal cardiac index (2.9 + 0.5 l/min/m(2)) in the setting of
      an elevated pulmonary capillary wedge pressure (PCWP 17 +/- 7 mmHg) and a normal
      pulmonary vascular resistance (122 + 70 dynes s cm(-5)). While PCWP, FEV(1)%
      predicted, and the minimum oxygen saturation in NREM sleep all independently
      predicted PH, PCWP was the most important predictor of PH. CONCLUSION: We
      conclude that pulmonary hypertension is commonly seen in patients with OSA with
      pretibial edema and that pretibial edema is a highly specific sign of PH in OSA
      patients. Pulmonary hypertension appears to result from an elevated back pressure
      and diastolic dysfunction with contributions from lung function and nocturnal
      oxygen saturation.

PMID- 18615261
TI  - Dietary n-3 HUFA affects mitochondrial fatty acid beta-oxidation capacity and
      susceptibility to oxidative stress in Atlantic salmon.
AB  - Atlantic salmon (Salmo salar) (90 g) were fed four different diets for 21 weeks
      (final weight 344 g). The levels of n-3 highly unsaturated fatty acids (HUFA)
      ranged from 11% of the total fatty acids (FA) in the low n-3 diet to 21% in the
      intermediate n-3 diet, to 55 and 58% in the high n-3 diets. The high n-3 diets
      were enriched with either docosahexaenoic acid (DHA) or eicosapentaenoic acid
      (EPA). Increasing dietary levels of n-3 HUFA led to increasing percentages (from
      31 to 52%) of these FA in liver lipids. The group fed the highest level of DHA
      had higher expressions of peroxisome proliferator-activated receptor (PPAR) beta
      and the FA beta-oxidation genes acyl-CoA oxidase (ACO) and carnitine
      palmitoyltransferase (CPT)-II, compared to the low n-3 groups. The high n-3
      groups had reduced activity of mitochondrial cytochrome c oxidase and beta
      oxidation capacity, together with increased activities of superoxide dismutase
      (SOD) and caspase-3 activities. In the group fed the highest level of n-3 HUFA,
      decreased percentages of major phospholipids (PL) in the mitochondrial and
      microsomal membranes of the liver were also apparent. The percentage of
      mitochondrial cardiolipin (Ptd(2)Gro) was 3.1 in the highest n-3 group compared
      to 6.6 in the intermediate group. These data clearly show an increased incidence
      of oxidative stress in the liver of fish fed the high n-3 diets.

PMID- 18615262
TI  - Physico-chemical characterisation of lipids from Mytilus galloprovincialis (L.)
      and Rapana venosa and their healing properties on skin burns.
AB  - Black Sea molluscs and gastropods are the most studied organisms from the
      Romanian littoral zone. In particular, those from the Mytilidae species are of
      great interest because biochemical investigations have shown that they can be
      sources of biological active substances which can have different applications
      (e.g. food additives). We report here the extraction of lipids from two different
      species of molluscs (Mytilus galloprovincialis L., Mediterranean mussel) and
      gastropods (Rapana venosa, hard-shell clam). The extracts were evaluated in terms
      of antioxidant and composition properties and their healing properties were
      tested on skin burns in Wistar rats. Our studies proved that the two lipid
      extracts contained a relatively complex distribution of compounds, in terms of
      characteristic indices, polyunsaturated fatty acids (PUFA) and vitamins E and D.
      The presence of such compounds rendered the extracts very efficient in healing
      induced skin burns in Wistar rats. The histological analysis showed a reduction
      in the time of healing (12-13 and 13-15 days for the Mytilus galloprovincialis
      (L.) Rapana venosa extracts, respectively) compared to 20-22 for untreated
      animals, based on results from tissues and blood samples. Our investigations have
      been proved to be promising in terms of future potential applications of the
      extracts as skin-care products, cosmetics and/or pharmaceutical preparations
      owing to their dermorestitutive properties.

PMID- 18615263
TI  - pH and expansin action on single suspension-cultured tomato (Lycopersicon
      esculentum) cells.
AB  - The aim of this study was to measure key material properties of the cell walls of
      single suspension-cultured plant cells and relate these to cell-wall
      biochemistry. To this end, micromanipulation was used to compress single tomato
      cells between two flat surfaces until they ruptured, and force-deformation data
      were obtained. In addition to measuring the bursting force, we also determined
      the elastic (Young's) modulus of the cell walls by matching low strain (< or =
      20% deformation) experimental data with a cell compression model, assuming linear
      elastic cell walls. The walls were most elastic at pH 4.5, the pH optimum for
      expansin activity, with an elastic modulus of 2.0 +/- 0.1 GPa. Following the
      addition of exogenous expansins, cell walls became more elastic at all pH values.
      Western blot analysis of proteins from walls of cultured cells revealed the
      presence of expansin epitopes, suggesting that the inherent pH dependence of
      elasticity and other compression phenomena is related to the presence of
      endogenous expansin proteins and their wall-loosening ability. Although strict
      application of the linear-elastic model could not be applied to large
      deformations-for example, up to cell bursting-because of irreversible behaviour,
      the deviation of the data from the model was generally small enough to allow
      estimation of the strain in the cell wall at failure. This strain was greater at
      pH 4.5 and when expansins were added to the suspension. The changes in elasticity
      are consistent with suggestions about the mode of expansin action. The estimated
      strains at failure are compatible with data on the failure of Acetobacter-derived
      cellulose-xyloglucan composites and proposed mechanisms of such failure. Through
      the measurement of cell-wall material properties using micromanipulation, it may
      be possible to understand more fully how cell-wall composition, structure and
      biochemistry lead to cell mechanical behaviour.

PMID- 18615264
TI  - Pollen morphology of the genus Skimmia (Rutaceae) and its taxonomic implications.
AB  - Pollen morphology of the genus Skimmia was studied. Of six species of the genus,
      five species were investigated by light microscopy and scanning electron
      microscopy. Pollen grains of Skimmia had striate to striate-reticulate sculpture
      and variable aperture number (3-7), and these characters differed from even the
      phylogenetically closest relatives such as Dictamnus and Casimiroa which have 3
      colporate pollen grains with reticulate exine. In Skimmia laureola, pollen
      dimorphism is suggested in the aperture number in accordance with the floral
      system. Pollen grains of Skimmia japonica, a morphologically very variable
      species, were extensively surveyed covering its whole distribution area. The
      grains were also striate to striate-reticulate, and the exine sculpture was not
      different between varieties. However, the aperture number of S. japonica showed a
      geographical variation ranging from 4 to 6; in Sakhalin, Hokkaido, most part of
      Honshu and Taiwan, grains with 4-5 apertures were dominant, while in the southern
      part of Japan, including the Ryukyu Islands and the Izu Islands, those with 5-6
      apertures were common.

PMID- 18615265
TI  - Large rivers do not always act as species barriers for Lepilemur sp.
AB  - Sportive lemurs constitute a highly diverse endemic lemur family (24 species) for
      which many biogeographic boundaries are not yet clarified. Based on recent
      phylogeographic models, this study aims to determine the importance of two large
      rivers (the Antainambalana and Rantanabe) in northeastern Madagascar as species
      barriers for Lepilemur seali. The Antainambalana River was previously assumed to
      act as the southern border of its distribution. A total of 1,038 bp of the mtDNA
      of four individuals stemming from two adjacent inter-river systems south of the
      Antainambalana River was sequenced and compared to sequences of 22 described
      Lepilemur species. The phylogenetic reconstruction did not find support for
      either of the two rivers as species barrier for Lepilemur, as all captured
      individuals clustered closely with and therefore belonged to L. seali. However, a
      previously published sequence of an individual from a site south of our study
      sites belongs to a separate species. The southern boundary of L. seali must
      therefore be one of two large rivers further south of our study sites. The
      results suggest that L. seali may possess a relatively large altitudinal range
      that enabled this species to migrate around the headwaters of the Antainambalana
      and Rantanabe Rivers. Previous phylogeographic models need to be refined in order
      to incorporate these findings, and more species-specific altitudinal range data
      are urgently needed in order to fully understand the biogeographic patterns of
      lemurs on Madagascar.

PMID- 18615268
TI  - CAL3JHH: a Java program to calculate the vicinal coupling constants (3J H,H) of
      organic molecules.
AB  - Here, we present a free web-accessible application, developed in the JAVA
      programming language for the calculation of vicinal coupling constant (3J(H,H))
      of organic molecules with the H-Csp3-Csp3-H fragment. This JAVA applet is
      oriented to assist chemists in structural and conformational analyses, allowing
      the user to calculate the averaged 3J(H,H) values among conformers, according to
      its Boltzmann populations. Thus, the CAL3JHH program uses the Haasnoot-Leeuw
      Altona equation, and, by reading the molecule geometry from a protein data bank
      (PDB) file format or from multiple pdb files, automatically detects all the
      coupled hydrogens, evaluating the data needed for this equation. Moreover, a
      "Graphical viewer" menu allows the display of the results on the 3D molecule
      structure, as well as the plotting of the Newman projection for the couplings.

PMID- 18615267
TI  - Differential genetic and environmental influences on reactive and proactive
      aggression in children.
AB  - While significant heritability for childhood aggression has been claimed, it is
      not known whether there are differential genetic and environmental contributions
      to proactive and reactive forms of aggression in children. This study quantifies
      genetic and environmental contributions to these two forms of aggression in an
      ethnically diverse urban sample of 9-10 year old twins (N = 1219), and compares
      results across different informants (child self-report, mother, and teacher
      ratings) using the Reactive-Proactive Aggression Questionnaire (RPQ).
      Confirmatory factor analysis of RPQ items indicated a significant and strong fit
      for a two-factor proactive-reactive model which was significantly superior to a
      one-factor model and which replicated across gender as well as the three
      informant sources. Males scored significantly higher than females on both self
      report reactive and proactive aggression, findings that replicated on mother and
      teacher versions of the RPQ. Asian-Americans scored lower than most ethnic groups
      on reactive aggression yet were equivalent to Caucasians on proactive aggression.
      African-Americans scored higher than other ethnic groups on all measures of
      aggression except caregiver reports. Heritable influences were found for both
      forms of aggression across informants, but while boys' self-reports revealed
      genetic influences on proactive (50%) and reactive (38%) aggression, shared and
      non-shared environmental influences almost entirely accounted for girls' self
      report reactive and proactive aggression. Although genetic correlations between
      reactive and proactive aggression were significant across informants, there was
      evidence that the genetic correlation was less than unity in boys self reported
      aggression, indicating that genetic factors differ for proactive and reactive
      aggression. These findings provide the first evidence for varying genetic and
      environmental etiologies for reactive and proactive aggression across gender, and
      provide additional support for distinction between these two forms of aggression.

PMID- 18615269
TI  - On the ability of 8-bromoadenosine triphosphate to support contractility of
      vertebrate skeletal muscle fibers.
AB  - Previous studies using solubilized fragments of myosins have shown that an ATP
      analogue, 8-bromoadenosine triphosphate (8-Br-ATP) is a poor substrate for fast
      skeletal myosin isoform. We further characterized the analogue by using
      vertebrate skeletal muscle fibers. In the absence of calcium, the rate of 8-Br
      ATP hydrolysis by fibers was higher than that for ATP, but it kept the fibers
      relaxed. The X-ray diffraction patterns of fibers relaxed by 8-Br-ATP were also
      indistinguishable from those of fibers relaxed by ATP, but higher concentrations
      were needed to keep the fibers relaxed. In the presence of calcium, the fibers
      exhibited force development and active shortening to varying extents. Although
      some of the energy for the observed contractility could be ascribed to the trace
      ATP in the reagents, the fibers activated in 8-Br-ATP performed much more
      mechanical work than expected from the energy of the trace ATP alone. The results
      suggest that most of the hydrolytic products of 8-Br-ATP dissociate from myosin
      prematurely, but a small fraction of myosin with these products does enter the
      calcium-dependent work-producing pathway and complete the normal process of chemo
      mechanical conversion.

PMID- 18615271
TI  - Separating gains and losses in health when calculating the minimum important
      difference for mapped utility measures.
AB  - OBJECTIVE: To estimate the minimum important difference (MID) for a variety of
      mapped utility measures and to determine whether patients perceiving gains and
      losses in health status should be treated equally when calculating the MID.
      METHODS: A longitudinal study within a California managed care population of
      6,932 patients was retrospectively analyzed. Utilities were derived from the SF
      36 short-form health survey using multiple validated mapping methods. Absolute
      utility changes for patients who considered their current health as 'somewhat
      better' or 'somewhat worse' in the prior year were compared to determine if gains
      and losses in utility values could be combined. The MIDs were calculated and
      compared using anchor- and distribution-based methods. RESULTS: Two thousand one
      hundred patients reported 'somewhat better' or 'somewhat worse' health in the
      first year. When combining these patients, the average MID for all mapped utility
      measures was 0.03 (SD=0.1), a magnitude similar to that identified by Walters.
      However, when separated, the mean MID utility change for those reporting
      'somewhat better' and 'somewhat worse' health was 0.02 (SD=0.1) and -0.06
      (SD=0.1), respectively (P<0.0001). CONCLUSIONS: Researchers should consider the
      effects of combining gains and losses when determining utility MID values.

PMID- 18615270
TI  - Left ventricular ejection fraction measurements: accuracy and prognostic
      implications in a large population of patients with known or suspected ischemic
      heart disease.
AB  - We sought to compare the reliability and prognostic implications of left
      ventricular (LV) ejection fraction (EF) measurements obtained in routine clinical
      practice. We retrospectively selected from our clinical database a group of 422
      patients with known or suspected ischemic heart disease, studied by two
      dimensional echocardiography, gated single-photon emission computed tomography
      (SPECT) and left ventriculography (LVG) for clinical purposes. In each diagnostic
      procedure LVEF was measured as done routinely. The LVEF values obtained by the
      three methods were similar and closely related. The correlation coefficient r was
      equal to 0.83 between echocardiographic and LVG, to 0.75 between gated SPECT and
      LVG and to 0.81 between echocardiographic and SPECT. During follow-up (median 41
      months), 31 patients died. The values of LVEF obtained by echocardiography, gated
      SPECT and LVG were all powerful predictors of all-cause mortality: chi(2) = 12.3
      for echocardiography, 14.4 for gated SPECT and 14.5 for LVG. However, including
      LVEF values into a model based on patient age, sex, history of angina, evidence
      of previous infarction and number of stenotic coronary arteries, the ability to
      predict patient survival significantly increased only including LVEF values
      measured by gated SPECT (chi(2) = 40.6, P = 0.039). Thus, in a large cohort of
      unselected patients with known or suspected ischemic heart disease, the values of
      LVEF routinely measured by echocardiography, gated SPECT and LVG were closely
      correlated, and provided a powerful prognostic information, that was incremental
      to clinical variables for gated SPECT.

PMID- 18615272
TI  - MLPA mutation detection in Argentine HNPCC and FAP families.
AB  - Colorectal cancer (CC) is the secondary cause of death in the Western countries
      of which approximately 15% are considered to be hereditary. The hereditary forms
      are Familial Adenomatous Polyposis (FAP) and Hereditary Non Polyposis Colorectal
      Cancer (HNPCC) which is the commonest form. The detection of mutations in the MMR
      and apc related genes, allows the development of health prevention strategies.
      Different molecular diagnostic strategies are available for the detection of
      mutations in these genes, i.e. DGGE, SSCP and direct sequencing. However,
      deletions and duplications of one or more consecutive exons, which account for
      around 50% of the total alterations in MMR genes, cannot be detected by PCR based
      methodologies due to the non quantitative nature of these techniques. The aim of
      our work has been the standardization of a methodology, called Multiplex Ligation
      Dependent Probe Amplification, which allows the detection of genomic deletions
      and duplications as primary analysis in HNPCC and FAP patients in Argentina. In
      this case, we inform that the application of MLPA allowed the detection of a
      missence mutation, without the need for direct sequencing of the complete genes
      involved. A PCR/RFLP strategy was afterwards designed to detect the C<T change on
      codon 718 of mlh1 gene in members of the family. For a developing country like
      Argentina, which has limited resources for genetic diagnosis, this MLPA
      application has avoided an unaffordable cost as the complete sequencing of all
      the involved genes. The application of MLPA in our country contributes to
      improvement in the diagnosis of hereditary CC and allows the development of
      preventive health interventions.

PMID- 18615273
TI  - Allosteric modulation of adenosine receptors.
AB  - Allosteric modulators for adenosine receptors may have potential therapeutic
      advantage over orthosteric ligands. Allosteric enhancers at the adenosine A(1)
      receptor have been linked to antiarrhythmic and antilipolytic activity. They may
      also have therapeutic potential as analgesics and neuroprotective agents. A(3)
      allosteric enhancers are postulated to be useful against ischemic conditions or
      as antitumor agents. In this review, we address recent developments regarding the
      medicinal chemistry of such compounds. Most efforts have been and are directed
      toward adenosine A(1) and A(3) receptors, whereas limited or no information is
      available for A(2A) and A(2B) receptors. We also discuss some findings, mostly
      receptor mutation studies, regarding localization of the allosteric binding sites
      on the receptors.

PMID- 18615274
TI  - Mentoring and research misconduct: an analysis of research mentoring in closed
      ORI cases.
AB  - We are reporting on how involved the mentor was in promoting responsible research
      in cases of research misconduct. We reviewed the USPHS misconduct files of the
      Office of Research Integrity. These files are created by Institutions who
      prosecute a case of possible research misconduct; ORI has oversight review of
      these investigations. We explored the role of the mentor in the cases of trainee
      research misconduct on three specific behaviors that we believe mentors should
      perform with their trainee: (1) review source data, (2) teach specific research
      standards and (3) minimize stressful work situations. We found that almost three
      quarters of the mentors had not reviewed the source data and two thirds had not
      set standards. These two behaviors are positively correlated. We did not see
      convincing evidence in the records that mentors were causing stress, but it was
      apparent in the convicted trainees' confessions that over 50% experienced some
      kind of stress. Secondary data, while not created for this research purpose,
      allows us to look at concrete research behaviors that are otherwise not very
      researchable. We believe it is important for mentors and institutions to devote
      more attention to teaching mentors about the process of education and their
      responsibilities in educating the next generation of scientists. This becomes a
      critical issue for large research groups who need to determine who is in charge
      educating, supervising and assuring data integrity.

PMID- 18615275
TI  - [Gender-related differences in functional assessment of serotonergic system in
      healthy young subjects].
AB  - INTRODUCTION: Prolactin stimulation test with serotonergic stimulants has been
      widely used in the study of diverse psychiatric disorders. However, the
      characterization of this response in normal subjects is still incomplete.
      OBJECTIVE: To compare the response to serotonin stimulation using
      dexfenfluramine, a specific serotonergic agent, in young healthy men and women,
      controlling the menstrual cycle. METHODS: A total of 10 women and 9 men, who were
      given 30 mg of dexfenfluramine orally, were studied and their levels of prolactin
      were measured on an hourly basis for a five-hour period. Baseline, maximum and
      delta values of prolactin were compared for both groups. RESULTS: According to
      the age groups studied (mean age for men: 19.9 +/- 2.5 years old; mean age for
      women: 20 +/- 1.5 years old), the prolactin maximum level and the response to
      prolactin (DPRL) were significantly higher in women (p-values: 0.02 and 0.04,
      respectively). CONCLUSIONS: Young healthy women show a greater response to
      stimulation with dexfenfluramine than young healthy men. Clinical and biological
      implications of this observation are discussed in the context of the currently
      available research papers.

PMID- 18615276
TI  - Reply to "steroids for caustic ingestions".

PMID- 18615277
TI  - Toxigenic fungi and mycotoxins in outdoor, recreational environments.
AB  - INTRODUCTION: Some epidemiological studies of damp buildings have focused on
      health risks from indoor exposure to toxigenic fungi and mycotoxins. Most of
      these studies have not considered assessment of these hazards in outdoor
      environments. The purpose of this investigation was to assess for toxigenic
      fungal species in outdoor recreational environments through the microbial
      analysis of locations representing opportunities for human exposure. A screening
      assessment was also conducted using commercially available ELISA kits to assess
      for trichothecene mycotoxins in outdoor samples. METHODS: Ten swab and tape-lift
      samples were obtained from a city park. Swabs were cultured and identified by a
      trained mycologist. Bulk samples of grasses were screened for deoxynivalenol
      using a commercial ELISA assay. A pilot study of 6 bulk samples was screened for
      macrocyclic trichothecenes using a commercial ELISA assay. RESULTS: Tape-lift
      samples contained trace to moderate spores. Penicillium and Aspergillus-like
      spores were identified in 50% of tape-lift samples. 50% of swab samples contained
      potentially toxigenic species of Penicillium (P. citrinum, P. brevicompactum, P.
      chrysogenum). None of the bulk samples tested positive for deoxynivalenol. 3 of 6
      (50%) bulk samples were positive for macrocyclic trichothecenes (> 0.2 ppb),
      however both negative control samples also tested positive. CONCLUSIONS:
      Potentially toxigenic fungi were commonly encountered in an outdoor, recreational
      environment. Future epidemiological studies need to consider outdoor activities
      in hazard and exposure assessment. Further work is needed to define the accuracy
      of commercially developed ELISA kits that are being used for the detection of
      mycotoxins in environmental samples.

PMID- 18615278
TI  - Antimicrobial activities of Gloriosa superba Linn (Colchicaceae) extracts.
AB  - The methanol extract of the rhizomes of Gloriosa superba Linn (Colchicaceae) and
      its subsequent fractions in different solvent systems were screened for
      antibacterial and antifungal activities. Excellent antifungal sensitivity was
      expressed by the n-butanol fraction against Candida albicans and Candida
      glaberata (up to 90%) and against Trichophyton longifusus (78%) followed by the
      chloroform fraction against Microsporum canis (80%). In the antibacterial
      bioassay, the crude extract and subsequent fractions showed mild to moderate
      antibacterial activities. Chloroform fraction displayed highest antibacterial
      sensitivity against Staphylococcus aureous (88%) followed by the crude extract
      (59%). The total phenol content of the crude extract and fractions of the plant
      expressed no significant correlation with the antimicrobial activities.

PMID- 18615279
TI  - New diterpenoid alkaloids from Aconitum heterophyllum Wall: Selective
      butyrylcholinestrase inhibitors.
AB  - Two new diterpenoid alkaloids, heterophyllinine-A (1) and heterophyllinine-B (2),
      along with two known alkaloids dihydroatisine (3) and lycoctonine (4) were
      isolated from the roots of Aconitum heterophyllum Wall. The structure of (1) and
      (2), were deduced on the basis of spectral data. Compounds 1-2 inhibited
      acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC
      3.1.1.8) enzymes in a concentration-dependent manner with percent inhibition
      ranging between 4.24% and 6.94 % and 79.1 % and 82.75 % for AChE and BChE,
      respectively indicating that compounds 1 and 2 are about thirteen times more
      specific to BChE than AChE.

PMID- 18615280
TI  - alpha-Glucosidase inhibitory activity of cyanidin-3-galactoside and synergistic
      effect with acarbose.
AB  - Cyanidin-3-galactoside, a natural anthocyanin, was investigated for its alpha
      glucosidase inhibitory activity. The IC(50) value of cyanidin-3-galactoside was
      0.50 +/- 0.05 mM against intestinal sucrase. A low dose of cyanidin-3-galactoside
      showed a synergistic inhibition on intestinal alpha-glucosidase (maltase and
      sucrase) when combined with acarbose. A kinetic analysis showed that cyanidin-3
      galactoside gave a mixed type inhibition against intestinal sucrase. The results
      indicated that cyanidin-3-galactoside was an alpha-glucosidase inhibitor and
      could be used in combination with acarbose for treatment of diabetes.

PMID- 18615281
TI  - Synthesis, spectral analysis, antibacterial and antifungal activities of some 4,6
      diaryl-4,5-dihydro-3-hydroxy-2[H]-indazole-a novel fused indazole derivative.
AB  - A novel class of 4,6-diaryl-4,5-dihydro-3-hydroxy-2[H]-indazoles 25-32 were
      synthesized and evaluated for their in vitro antibacterial and antifungal
      activities. Four Compounds, which all possessed electron withdrawing functional
      groups (-Cl, -NO(2), -Br) 27, 28, 30 and 32 were more potent against the tested
      bacterial/fungal strains than the standard bacterial and fungal drugs
      ciprofloxacin and fluconazole respectively.

PMID- 18615282
TI  - Synthesis, physico-chemical characterization and antimicrobial activity of
      cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes with some
      acyldihydrazones.
AB  - Complexes of the type [M(bssdh)]Cl and [M(dspdh)]Cl, where M = Co(II), Ni(II),
      Cu(II), Zn(II) and Cd(II); Hbssdh = benzil salicylaldehyde succinic acid
      dihydrazone, Hdspdh = diacetyl salicylaldehyde phthalic acid dihydrazone have
      been synthesized and characterized with the help of elemental analyses,
      electrical conductance, magnetic susceptibility measurements, electronic, ESR and
      IR spectra and X-ray diffraction studies. Magnetic moment values and electronic
      spectral transitions indicate a spin free octahedral structure for Co(II), Ni(II)
      and Cu(II) complexes. IR spectral studies suggest that both the ligands behave as
      monobasic hexadentate ligands coordinating through three > C = O, two > C = N-
      and a phenolate group to the metal. ESR spectra of Cu(II) complexes are axial
      type and suggest d(x(2)-y(2)) as the ground state. X-ray powder diffraction
      parameters for [Co(bssdh)]Cl and [Co(dspdh)]Cl complexes correspond to an
      orthorhombic crystal lattice. The ligands as well as their metal complexes show a
      significant antifungal and antibacterial activity against various fungi and
      bacteria. The metal complexes are more active than the parent ligands.

PMID- 18615283
TI  - Photometric microplate assay for estimation of the efficacy of paraoxon-inhibited
      acetylcholinesterase reactivation.
AB  - Photometric microplate assay was performed for testing of paraoxon-inhibited
      acetylcholinesterase (AChE) using three reactivators for reactivation purposes:
      obidoxime, pralidoxime, and HI-6. 3-D graphs (percent of reactivation vs.
      concentration of reactivator and vs. time of reactivator effecting) were
      constructed for each reactivator to compare their efficacy. The best results were
      obtained using obidoxime where reactivation was near to 80%. Suitability of
      photometric microplates for following of reactivation procedures is discussed.

PMID- 18615284
TI  - Design and synthesis of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4
      ones as a novel class of analgesic and anti-inflammatory agents.
AB  - A new series of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones were
      synthesized by reacting the amino group of 2-hydrazino-3-(4-ethylphenyl)-3H
      quinazolin-4-one from 4-ethyl aniline with a variety of aldehydes and ketones.
      The title compounds were investigated for analgesic, anti-inflammatory and
      ulcerogenic index activities. The compound 2-(N'-3-pentylidene-hydrazino)-3-(4
      ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound of the
      series and was moderately more potent than the reference standard diclofenac
      sodium. Interestingly the test compounds showed only mild ulcerogenic potential
      when compared to aspirin.

PMID- 18615285
TI  - Chlorpromazine oligomer is a potentially active substance that inhibits human D
      amino acid oxidase, product of a susceptibility gene for schizophrenia.
AB  - D-amino acid oxidase (DAO), a potential risk factor for schizophrenia, has been
      proposed to be involved in the decreased glutamatergic neurotransmission in
      schizophrenia. Here we show the inhibitory effect of an antipsychotic drug,
      chlorpromazine, on human DAO, which is consistent with previous reports using
      porcine DAO, although human DAO was inhibited to a lesser degree (K(i) = 0.7 mM)
      than porcine DAO. Since chlorpromazine is known to induce phototoxic or
      photoallergic reactions and also to be transformed into various metabolites, we
      examined the effects of white light-irradiated chlorpromazine on the enzymatic
      activity. Analytical methods including high-resolution mass spectrometry revealed
      that irradiation triggered the oligomerization of chlorpromazine molecules. The
      oligomerized chlorpromazine showed a mixed type inhibition with inhibition
      constants of low micromolar range, indicative of enhanced inhibition. Taken
      together, these results suggest that oligomerized chlorpromazine could act as an
      active substance that might contribute to the therapeutic effects of this drug.

PMID- 18615286
TI  - Lipoxygenase inhibition by novel fatty acid ester from Annona squamosa seeds.
AB  - Studies on the seeds of Annona squamosa yielded a novel lipoxygenase inhibitor
      fatty acid ester, (+) - annonlipoxy (1). Compound 1 was screened for its enzyme
      inhibitory activity against lipoxygenase (E.C.1.14.18.1), exhibiting activity
      with IC(50) 69.05 +/- 5.06 microm. Baicalein (IC(50) 22.6 +/- 0.5 microm) was
      used as a positive control. Crude extracts of Annona squamosa fruit pulp and
      seeds were screened for its enzyme inhibitory activity against lipoxygenase and
      acetylcholinesterase. The crude ethanolic extract of fruit pulp and seeds of
      Annona squamosa also exhibited lipoxygenase activity with 22.2 and 26.7%
      inhibition, while the pet.ether extract of seeds of A. squamosa exhibited 52.7%
      inhibition at a concentration of 40 microg/200 ml. The crude ethanolic extract of
      seeds of Annona squamosa was also bioassayed for acetylcholinesterase inhibition
      and it was found inactive.

PMID- 18615287
TI  - Urease and serine protease inhibitory alkaloids from Isatis tinctoria.
AB  - Phytochemical investigations on the alkaloidal fraction of the whole plant of the
      Isatis tinctoria led to the isolation of the alkaloids 1-6., 3'
      Hydroxyepiglucoisatisin (3), Epiglucoisatisin (2) were found to be potent urease
      inhibitors in a concentration-dependent manner with IC(50) values 25.63 +/- 0.74,
      37.01 +/- 0.41 and 31.72 +/- 0.93, 47.33 +/- 0.31 microM against Bacillus
      pasteurii & Jack bean urease, respectively. Compounds 3 and 2 also showed potent
      inhibitory potential against alpha-chymotrypsin with IC(50) values of 23.40 +/-
      0.21 and 27.45 +/- 0.23 microM, respectively.

PMID- 18615288
TI  - Alkaline phosphatase inhibition by vanadyl-beta-diketone complexes: electron
      density effects.
AB  - A series of systematically modified vanadyl-beta-diketone complexes, VO(beta
      diketone)(2), bearing substituent groups with different electron inductive
      properties were synthesized and evaluated as inhibitors against calf-intestine
      alkaline phosphatase (APase). A combination of biochemical and quantum mechanical
      techniques were employed to identify structure-activity relationships relevant
      for rational design of phosphatase inhibitors. Kinetic parameters and activation
      free energy, enthalpy, and entropy for calf-intestine APase-catalyzed
      dephosphorylation of para-nitrophenylphosphate were also determined along with
      the inhibition constants (K(i)) for the VO(beta-diketone)(2) complexes. Increased
      positive charge on the vanadyl group increases the inhibition potency of the
      complex while the absence of an available coordination site on the complex
      decreases its inhibition potency. These findings correlate well with the results
      of ab initio electron density calculations for the complexes.

PMID- 18615289
TI  - Effect of alginate-pectin composition on drug release characteristics of
      microcapsules.
AB  - Microencapsulation of model drug, acetylsalicylic acid into bio-based polymer,
      alginate-pectin matrix has been undertaken in this work to characterize the
      microcapsules based on their composition. Different proportions of the alginate
      pectin solutions prepared with drug were homogenized and atomized using nitrogen
      gas into 1.0 M calcium chloride solution to form sol-gel microcapsules. Drug
      loaded microcapsules were dried using microwave energy under vacuum at low
      temperature. Average particle size of the microcapsules was found to be 90
      micron. Scanning electron microscopy graphs and Fourier Transform Infrared
      Spectroscopy analysis on the microcapsules confirm the presence of drug in the
      polymer matrix. X-ray diffraction pattern showed that the microstructure was more
      like an amorphous pattern. Drug release of the microcapsules was tested in three
      different pH levels of 1.2, 7.4 and 8.2. Slow and controlled release of drug was
      observed at all the pH levels. Increase in pectin increased the drug release and
      also the release was more in acidic pH (1.2) as 75.6% for alginate: pectin-20:80.

PMID- 18615290
TI  - Occupational exposures associated with petroleum-derived products containing
      trace levels of benzene.
AB  - Benzene may be present as a trace impurity or residual component of mixed
      petroleum products due to refining processes. In this article, the authors review
      the historical benzene content of various petroleum-derived products and
      characterize the airborne concentrations of benzene associated with the typical
      handling or use of these products in the United States, based on indoor exposure
      modeling and industrial hygiene air monitoring data collected since the late
      1970s. Analysis showed that products that normally contained less than 0.1% v/v
      benzene, such as paints and paint solvents, printing solvents and inks, cutting
      and honing oils, adhesives, mineral spirits and degreasers, and jet fuel
      typically have yielded time-weighted average (TWA) airborne concentrations of
      benzene in the breathing zone and surrounding air ranging on average from <0.01
      to 0.3 ppm. Except for a limited number of studies where the benzene content of
      the product was not confirmed to be <0.1% v/v, airborne benzene concentrations
      were also less than current occupational exposure limits (e.g., threshold limit
      value of 0.5 ppm and permissible exposure limit of 1.0 ppm) based on exceedance
      fraction calculations. Exposure modeling using Monte Carlo techniques also
      predicted 8-hr TWA near field airborne benzene concentrations ranging from 0.002
      to 0.4 ppm under three hypothetical solvent use scenarios involving mineral
      spirits. The overall weight-of-evidence indicates that the vast majority of
      products manufactured in the United States after about 1978 contained <0.1% v/v
      benzene, and 8-hr TWA airborne concentrations of benzene in the workplace during
      the use of these products would not have been expected to exceed 0.5 ppm under
      most product use scenarios. [Supplementary materials are available for this
      article. Go to the publisher's online edition of Journal of Occupational and
      Environmental Hygiene for the following free supplemental resource: a document
      containing exposure modeling scenarios and results, historical benzene content of
      petroleum-derived products, and air monitoring results.].

PMID- 18615291
TI  - Comparison of task-based exposure metrics for an epidemiologic study of
      isocyanate inhalation exposures among autobody shop workers.
AB  - Because many occupational epidemiologic studies use exposure surrogates rather
      than quantitative exposure metrics, the UMass Lowell and Yale study of autobody
      shop workers provided an opportunity to evaluate the relative utility of
      surrogates and quantitative exposure metrics in an exposure response analysis of
      cross-week change in respiratory function. A task-based exposure assessment was
      used to develop several metrics of inhalation exposure to isocyanates. The
      metrics included the surrogates, job title, counts of spray painting events
      during the day, counts of spray and bystander exposure events, and a quantitative
      exposure metric that incorporated exposure determinant models based on task
      sampling and a personal workplace protection factor for respirator use, combined
      with a daily task checklist. The result of the quantitative exposure algorithm
      was an estimate of the daily time-weighted average respirator-corrected total NCO
      exposure (microg/m(3)). In general, these four metrics were found to be variable
      in agreement using measures such as weighted kappa and Spearman correlation. A
      logistic model for 10% drop in FEV(1) from Monday morning to Thursday morning was
      used to evaluate the utility of each exposure metric. The quantitative exposure
      metric was the most favorable, producing the best model fit, as well as the
      greatest strength and magnitude of association. This finding supports the reports
      of others that reducing exposure misclassification can improve risk estimates
      that otherwise would be biased toward the null. Although detailed and
      quantitative exposure assessment can be more time consuming and costly, it can
      improve exposure-disease evaluations and is more useful for risk assessment
      purposes. The task-based exposure modeling method successfully produced estimates
      of daily time-weighted average exposures in the complex and changing autobody
      shop work environment. The ambient TWA exposures of all of the office workers and
      technicians and 57% of the painters were found to be below the current U.K.
      Health and Safety Executive occupational exposure limit (OEL) for total NCO of 20
      microg/m(3). When respirator use was incorporated, all personal daily exposures
      were below the U.K. OEL.

PMID- 18615292
TI  - Predicting benzene vapor concentrations with a near field/far field model.
AB  - Published data on benzene vapor concentrations in work simulation settings were
      used to examine the predictive ability of a near field/far field vapor dispersion
      model with an exponentially decreasing vapor emission rate. A given simulation
      involved two 15-min periods of applying a known volume of benzene-containing
      liquid to equipment on a worktable in a room with a measured air exchange rate.
      Replicate personal breathing zone (15-min time-weighted average, TWA) and room
      area (1-hr TWA) air samples were collected. In our modeling, the benzene vapor
      concentration in the near field zone (at the worktable) represented the personal
      breathing zone exposure level, and the benzene vapor concentration in the far
      field zone represented the room area concentration. Across 10 simulation
      combinations of two factors (the mass of benzene applied and the room air
      exchange rate), the mean of the personal breathing zone exposure levels ranged
      from 0.2 to 9.9 mg m(-3), and the mean of the room area concentrations ranged
      from 0.05 to 5.05 mg m(-3). Our model provided reasonably accurate estimates of
      the measured benzene vapor concentrations. Linear regression of the mean measured
      personal breathing zone exposure versus the predicted near field concentration
      yielded slope = 0.93 and r(2) = 0.94; the null hypothesis that the true slope
      equals one was not rejected (p-value = 0.39). Linear regression of the mean
      measured room area concentration versus the predicted far field concentration
      yielded slope = 0.90 and r(2) = 0.94; the null hypothesis that the true slope
      equals one was not rejected (p-value = 0.20). Other statistical tests showed no
      significant differences between measured and predicted values. In addition, most
      predicted concentrations fell within an approximate range of one-half to twofold
      the respective measured concentrations.

PMID- 18615293
TI  - Do fears of malpractice litigation influence teaching behaviors?
AB  - BACKGROUND: Medical malpractice is prominently positioned in the consciousness of
      American physicians, and the perceived threat of malpractice litigation may push
      physicians to practice defensively and alter their teaching behaviors. PURPOSE:
      The purposes of this study were to characterize the attitudes of academic medical
      faculty toward malpractice litigation and to identify teaching behaviors
      associated with fear of malpractice litigation. METHODS: We surveyed 270 full
      time clinically active physicians in the Department of Medicine at a large
      academic medical center. The survey assessed physicians' attitudes toward
      malpractice issues, fear of malpractice litigation, and self-reported teaching
      behaviors associated with concerns about litigation. RESULTS: Two hundred and
      fifteen physicians responded (80%). Faculty scored an average of 25.5 +/- 6.9
      (range = 6-42, higher scores indicate greater fear) on a reliable malpractice
      fear scale. Younger age (Spearman's rho = 0.19, p = .02) and greater time spent
      in clinical activities (rho = 0.26, p < .001) were correlated with higher scores
      on the Malpractice Fear Scale. Faculty reported that because of the perceived
      prevalence of lawsuits and claims made against physicians, they spend more time
      writing clinical notes for patients seen by learners (74%), give learners less
      autonomy in patient care (44%), and limit opportunities for learners to perform
      clinical procedures (32%) and deliver bad news to patients (33%). Faculty with
      higher levels of fear on the Malpractice Fear Scale were more likely to report
      changing their teaching behaviors because of this perceived threat (rho = 0.38, p
      < .001). CONCLUSIONS: Physicians report changes in teaching behaviors because of
      concerns about malpractice litigation. Although concerns about malpractice may
      promote increased supervision and positive role modeling, they may also limit
      important educational opportunities for learners. These results may serve to
      heighten awareness to the fact that teaching behaviors and decisions may be
      influenced by the malpractice climate.

PMID- 18615294
TI  - Simpler standards for local performance examinations: the Yes/No Angoff and whole
      test Ebel.
AB  - BACKGROUND: The whole-test Ebel and Yes/No Angoff methods offer the possibility
      of faster and easier standard-setting exercises for local, medium-stakes
      performance exams. PURPOSE: We sought to establish if these less demanding
      methods might be substituted for the traditional but complex case-level Ebel.
      METHODS: Six faculty judges each used all three methods to set standards for six
      standardized-patient checklists used for 178 fourth-year medical students. We
      compared the cut scores, passing rates, reliability, ease of use, and credibility
      of the three methods. RESULTS: The three methods produced roughly equivalent cut
      scores. Generalizability of judgments was .94 and .96 for the case-level and
      whole-test Ebel, and .76 for the Yes/No Angoff. Judges found the simplified
      methods more credible than the case-level Ebel. The Yes/No Angoff method was
      preferred by five of six judges. CONCLUSIONS: The whole-test Ebel and the Yes/No
      Angoff may be simple and realistic options for setting standards for local
      performance exams.

PMID- 18615295
TI  - A randomized controlled study comparing educational outcomes of examination room
      versus conference room staffing.
AB  - BACKGROUND: This prospective randomized controlled study examined outpatient
      clinical teaching in the presence of the patient. METHODS: In 2006, patients in
      ambulatory internal medicine clinics at the University of Iowa were randomized to
      have faculty-learner presentations either in their presence or in the conference
      room. Staffing encounters were timed and faculty, learners and patients completed
      postencounter surveys. RESULTS: Participation included 254 patients and 12
      faculty. Comparison of patient encounters randomized to exam room (n = 120) or
      conference room (n = 134) staffing demonstrated increased time spent with the
      patient in exam room staffing (91% vs. 54% of total staffing time; p < .0001) but
      no significant differences in mean total staffing time. Patients, learners, and
      faculty preferred exam room staffing. CONCLUSIONS: Concerns about time efficiency
      and patient and learner satisfaction during exam room staffing were not
      supported. This approach may allow attending physicians to maximize billing
      levels while increasing learner/patient involvement.

PMID- 18615296
TI  - Scores from riding's cognitive styles analysis have poor test-retest reliability.
AB  - BACKGROUND: The Cognitive Styles Analysis (CSA) purports to assess two cognitive
      style dimensions, wholist-analytic (WA) and verbalizer-imager (VI). CSA score
      reliability has not been studied in medical education. PURPOSE: The objective of
      this study was to evaluate test-retest reliability and learner-perceived accuracy
      of CSA scores. METHOD: CSA scores were measured twice and perceived accuracy of
      classifications once among 89 family medicine residents, internal medicine
      residents, and medical students. RESULTS: Mean +/- standard deviation interval
      between tests was 564 +/- 136 days. Test-retest correlation for WA scores was
      0.30, and for VI scores was 0.12. Upon retesting 44 learners (49%) were
      classified under a different WA style, and 56 learners (63%) were classified
      under a different VI style. There were 58 of 73 learners (79%) who agreed or
      strongly agreed with their WA classification, whereas 51 of 76 (67%) agreed with
      their VI classification. CONCLUSIONS: CSA scores have poor test-retest
      reliability. Educators may wish to avoid using the CSA and should exercise
      caution when interpreting CSA scores.

PMID- 18615297
TI  - Career guidance and the Web: bridging the gap between the AAMC careers in
      Medicine Web site and local career guidance programs.
AB  - BACKGROUND: Medical students face a difficult challenge choosing a specialty. The
      Web offers several advantages in guiding students in the decision-making process.
      DESCRIPTION: The Vanderbilt University School of Medicine created a school
      specific Web site to complement the Association of American Medical College's
      Careers in Medicine program. The goals were: connecting students with institution
      specific resources, providing students with information on specialty choices and
      residency preparation, and promoting an interactive Web-based tool. A student
      team developed the Web site over several months. The site incorporates tracking
      tools to assess usage. During the first 240 days of use, the Web site has had
      3,782 sessions viewing 29,864 Web pages. Monthly usage has trended upward.
      CONCLUSIONS: Using the Web to provide school-specific career information can
      guide students in the difficult process of specialty selection. Future studies
      are required to assess the Web site's overall effectiveness and overall student
      satisfaction.

PMID- 18615298
TI  - Debate preparation/participation: an active, effective learning tool.
AB  - BACKGROUND: Passive educational techniques (such as lectures) are thought to be
      less productive than active learning. PURPOSE: We examined whether preparing for
      and participating in a debate would be an effective, active way to learn about a
      controversial topic. METHODS: We compared quiz performance in residents who
      attended a lecture to residents who prepared for/participated in a debate. Twelve
      residents each participated in one lecture session and one debate session.
      Learning was evaluated via a quiz. Quizzes were given twice: before the
      debate/lecture and 1 week after the debate/lecture. Quiz scores were compared
      using repeated measures analysis of variance, with a p value of < .05 considered
      significant. A survey evaluating the usefulness of debating was given to all
      participants. RESULTS: There was a statistically significant difference in the
      pretest mean quiz score between the debate and lecture groups: 78.3% and 52.5%,
      respectively (p = .02). Similarly, on posttest quizzes, the average debater
      scored 85.8%, versus 61.7% for the lecture group (p = .003). Although no one in
      the debate group scored lower on a follow-up quiz, 3 residents in the lecture
      group did worse on follow-up. CONCLUSIONS: When learning about a controversial
      topic, residents who prepared for/participated in a debate achieved higher quiz
      scores and were better at retaining information than those who attended a
      lecture. When faced with teaching a controversial topic, organizing a debate may
      be more effective than giving a lecture.

PMID- 18615299
TI  - Do different pairings of teaching styles and learning styles make a difference?
      Preceptor and resident perceptions.
AB  - BACKGROUND: Certain teaching style (TS) and learning style (LS) combinations may
      enhance learning. PURPOSE: The objective was to examine the effects of
      combinations of TS and LS in preceptor-resident (PR-RE) dyads in a long-term
      teaching-learning environment. METHODS: Forty-four pediatric PR-RE pairs
      responded to Grasha's TS and LS inventories, the Clinical Teacher Characteristics
      Instrument (CTCI) and the Preceptor-Resident Relationship Inventory (PRPRI).
      Combined CTCI and PRRI means were compared using the t test. RESULTS: The
      facilitator or personal model TS and collaborative LS pairs supported a healthy
      teaching-learning environment. Independent learners rated their preceptors'
      teaching characteristics positively. Competitive LS residents rated the
      relationship with the preceptor and preceptor teaching effectiveness less
      favorably. Residents overall indicated a less favorable relationship and clinical
      teaching characteristics than preceptors. CONCLUSIONS: Certain combinations of TS
      with LS are perceived by preceptors and residents as more positive than others.
      This suggests TS and LS should be considered when pairing residents and
      preceptors.

PMID- 18615300
TI  - A critical intervention in lesbian, gay, bisexual, and transgender health:
      knowledge and attitude outcomes among second-year medical students.
AB  - BACKGROUND: Lesbian, gay, bisexual, and transgender (LGBT) persons represent an
      underserved population susceptible to health care disparities. DESCRIPTION: In
      February 2004, we implemented an LGBT health curriculum for students at the
      University of California at San Francisco. Confidential matched questionnaires
      elicited students' knowledge, attitudes, and beliefs about LGBT health issues
      before and after the intervention. EVALUATION: The surveyed population (52%
      response rate) was demographically similar to the entire class. There was
      statistically significant change in the responses to 4 of 16 questionnaire items
      (p <or= .001; largest absolute change was 0.57 on a 5-point scale). Students
      demonstrated increased knowledge about access to health care and LGBT
      relationships, increased willingness to treat patients with gender identity
      issues, and enhanced awareness that sexual identity and practices are clinically
      relevant. CONCLUSIONS: Our simple curricular intervention led to significant
      short-term changes in a small number of survey items assessing students'
      knowledge and beliefs about LGBT persons.

PMID- 18615301
TI  - A departmental experience in promoting oral and poster presentations.
AB  - BACKGROUND: Residency programs must demonstrate resident and faculty involvement
      in scholarly activity. One acceptable method is delivering presentations at
      scientific meetings. DESCRIPTION: A prospective database and retrospective search
      of all prior presentations. EVALUATION: Prior to 1997, residents made less than 5
      presentations per year. After inception, they made an average of 35, increasing
      from 12 in 1998 to 80 in 2006; 180 submissions were presented 335 times (1.9
      presentations per unique work). The majority were based on case reports, whereas
      11% were research. In the last 2 years, 36% were accepted as oral presentations,
      the remaining as posters. Total program cost for 2006 was $39,184 ($490 per
      presentation). CONCLUSION: The program has succeeded in increasing scholarly
      activity for faculty and residents at an acceptable cost. Most secondary goals
      were also met, including increasing the number of departmental publications.

PMID- 18615302
TI  - Clinical location and student learning: outcomes from the LCAP program in
      Queensland, Australia.
AB  - BACKGROUND: Three students in the 3rd year of a graduate entry medical program
      self-selected to participate in a 1-year clinical placement, each with a rural
      general practitioner in central western Queensland, Australia. DESCRIPTION:
      Students completed 32 weeks in a rural generalist community immersion medical
      program and were compared with matched students who completed their year in urban
      tertiary hospitals. Evaluations included teaching and learning opportunities,
      assessment of clinical competencies, and semistructured interviews. Views of
      preceptors, spouses, and community were also evaluated. EVALUATION: All outcome
      measures were positive and many were greater for the rural immersion students
      than for the matched urban group. Students were able to achieve the requirements
      of their medical program in a nontraditional placement. Views of preceptors
      indicated satisfaction with long-term medical student placements including
      enjoyment, negligible time or financial impact, and beneficial professional and
      collegial support. CONCLUSIONS: Long-term immersion placements benefited student
      learning and had a favorable impact on the preceptors.

PMID- 18615303
TI  - Does student promotions committee appearance predict below-average performance
      during internship? A seven-year study.
AB  - BACKGROUND: Medical educators grapple with predicting performance of graduates
      identified as struggling during medical school. Students appear before student
      promotions committees (SPCs) for multiple cognitive and noncognitive reasons and
      performance outcomes for this cohort have not been well defined in the
      literature. PURPOSE: To determine the predictive validity of SPC appearance with
      respect to performance on a Program Director's (PD's) Evaluation Form completed
      at the end of internship (PGY-1). METHOD: Residents were classified as "below
      average," "average," or "above average" based on PD Evaluation Form ratings. This
      PD instrument has been shown to be feasible, reliable, and valid. Below-average
      residents were defined as having a below-average rating on any question on the PD
      Evaluation Form. We compared SPC and non-SPC cohorts with respect to these PD
      Evaluation Form ratings. The t test was used for statistical analysis. RESULTS:
      Seven years of graduating classes from our institution were included. Of students
      who graduated from our institution, 119 of 856 students (14%) were presented at
      our SPC during medical school during our study period. There were 196 residents
      (23%) identified as below average. The PD Evaluation Form response rate for this
      period was 77%. Students who appeared at our SPC were significantly more likely
      to have below-average scores for almost all PD Evaluation Form questions with
      small to moderate effect sizes. CONCLUSIONS: Students who appear before SPCs are
      at higher risk of below-average performance as rated by a PD Evaluation Form at
      the end of PGY-1. However, only a minority of trainees that appeared before our
      SPC received below-average ratings during internship. These data provide
      predictive validity evidence that SPC appearance during medical school does
      identify below average performance during internship. Our data support that SPC
      appearance during medical school, regardless of cause, is a risk for below
      average performance during internship.

PMID- 18615304
TI  - Gender and academic medicine: a good pipeline of women graduates is not
      advancing.
AB  - BACKGROUND: Women are underrepresented in the higher levels of appointment in
      academic medicine, despite the so-called feminization of medicine. PURPOSE: A 27
      year (1979-2006) retrospective study was conducted regarding the success and
      advancement of women and men at the University of Split School of Medicine in
      Croatia. METHODS: Data were collected from the school's archive, including number
      of women and men among applicants, enrollees, graduates, teachers, department
      chairs and the school management: high school grade averages and admission tests
      scores by applicant gender and gender-based graduation grade averages. The number
      and gender patterns of all employed and unemployed physicians in the Split
      Dalmatia county were also collected. RESULTS: Men represent the minority among
      applicants, enrollees, and graduates, whereas women were in the minority among
      faculty, department chairs, and the school management across all 27 years.
      Graduation grades from high school and medical school showed that women were
      statistically better students, although the difference was slight. In the same
      geographic area, women are more often unemployed and less likely to specialize.
      CONCLUSIONS: More women are applying, enrolling and graduating from the
      University of Split School of Medicine. Women also perform statistically better
      on entrance exam and have better graduation grades, yet they remain a minority in
      faculty and leadership positions. A review of county-wise employment statistics
      revealed that women were more frequently unemployed and less likely to specialize
      in this study.

PMID- 18615305
TI  - Changes in medical students' emotional intelligence: an exploratory study.
AB  - BACKGROUND: The ability to recognize and adapt to affective states in one's self
      and others, emotional intelligence is thought to connote effective, compassionate
      doctor-patient communication. Unfortunately, medical training has been shown to
      erode some of the very attributes it purports to instill in students. PURPOSE:
      The objective is to examine changes in students' emotional intelligence and
      empathy across an undergraduate medical curriculum. METHODS: During M1
      orientation and again following M3 clerkship training, students in the University
      of Kentucky College of Medicine Class of 2004 completed the Trait Meta-Mood Scale
      (TMMS) and Davis' Interpersonal Reactivity Index (IRI). Baseline changes in
      specific dimensions were examined for both male and female students. RESULTS:
      Reliability of subscales was generally acceptable (alpha >or= .70). Sixty-four
      students provided data at both time points. Compared to baseline, two of three
      TMMS dimensions--attention to feelings and mood repair--were significantly (p
      <or= .05) lower at follow-up. One IRI dimension--empathic concern--was also
      significantly lower at Time 2, whereas another, Personal Distress, was
      significantly higher. However, differences generally reflected only small effect
      sizes. No significant gender interactions were noted. CONCLUSIONS: Despite quite
      modest effect sizes, findings suggest that students' abilities to effectively
      manage affective states may be subject to some minor fluctuation across the
      undergraduate educational continuum. However, whether these observed declines
      constitute meaningful, clinically relevant changes remains unclear.

PMID- 18615308
TI  - An assessment of anxiolytic drug screening tests: hormetic dose responses
      predominate.
AB  - This article provides a comprehensive assessment of dose response relationships
      for anxiolytic (i.e., anxiety-reducing) agents within a broad representation of
      the animal model screening tests. These screening tests include the elevated plus
      maze test, light-dark test, hole board test, open field test, four plates test,
      social interaction test, Vogel's conflict test, staircase test, freeze behavior
      test, forced swimming test, tail suspension test, communication box test, and
      immobilization/cold stress test. The analysis revealed that hormetic-like
      biphasic dose responses were commonly observed across all screening tests,
      independent of the animal model, the conditions of the test, modifications of
      tests by investigators, and the chemical class of agents tested. The quantitative
      features of the dose response, as measured by the magnitude and width of the
      stimulation at low doses, were similar across all screening tests and
      experimental conditions, regardless of the mechanism and receptor activation
      pathway identified. These findings, which add more support to the perspective
      that the hormetic dose response represents the most fundamental and common dose
      response model in the biomedical and toxicological sciences, have important
      implications for the process of drug discovery/development, clinical evaluation,
      and quantitative expectation of drug treatment effects.

PMID- 18615309
TI  - Modulation of the epileptic seizure threshold: implications of biphasic dose
      responses.
AB  - Considerable evidence has emerged that hormetic-like biphasic dose-response
      relationships are common in the biomedical sciences. Consequently, this article
      assesses dose-response relationships of agents known to modulate epileptic-like
      seizure thresholds in screening tests with animal models. Biphasic dose responses
      have been commonly reported as measured by changes in seizure threshold
      concentrations across a broad dose-response continuum of chemically diverse
      agents that act via different receptor-based mechanisms. Despite such differences
      in chemical structure and modes of actions, the quantitative features of these
      dose responses are quite similar, being consistent with the hormetic dose
      response model with respect to the magnitude and width of the stimulatory
      responses. The hormetic responses were also independent of the animal model
      employed as well as type of seizure-related endpoint measured. These findings
      support the generalizability of the hormetic dose-response concept and may have
      important implications for the discovery of antiseizure drugs and their clinical
      evaluation.

PMID- 18615310
TI  - Drug therapies for stroke and traumatic brain injury often display U-shaped dose
      responses: occurrence, mechanisms, and clinical implications.
AB  - This article explores the occurrence of U-shaped dose responses induced by
      neuroprotective agents in animal stroke and traumatic brain injury (TBI)
      screening/preclinical studies. The assessment was stimulated by suggestions that
      U-shaped dose responses may be common for neuroprotective agents in stroke and
      TBI models, and its lack of both recognition and understanding may be a factor
      contributing to the failure of many promising drugs to be protective in clinical
      trials. Over 30 agents with neuroprotective properties in animal stroke/TBI
      models were identified that act via U-shaped dose responses in a broad range of
      experimental protocols. These findings suggest that U-shaped dose responses in
      animal stroke/TBI models may be a general occurrence and have significant
      implications for drug discovery, drug development, and clinical practice.

PMID- 18615311
TI  - Surgical revolutions.
AB  - Many surgical revolutions distinguish the history and evolution of surgery. They
      come in different sizes and exert a variable effect on the development and
      practice of the discipline. As science and technology rapidly evolve, so too does
      the creation of new paradigms, ideas and innovations or discoveries for the
      improvement of the surgical sciences. Surgical revolutions are not new, and have
      existed for centuries even though they have been more frequently recognized since
      the middle of the 19th century, 20th century and down to the present. Surgical
      revolutionaries are indispensable in the conception and completion of any
      surgical revolution. However, scientific and technological advances have
      supported the culmination of each revolution.

PMID- 18615312
TI  - Hans Jurgen Bretschneider: German surgical research pioneer.

PMID- 18615313
TI  - Resterilized mesh in repair of abdominal wall defects in rats.
AB  - A variety of negative opinions about repeated usage of relatively expensive
      resterilized synthetic meshes have been considered. It had been stated that
      resterilized polypropylene meshes inhibits fibroblastic activity, decreases
      proliferative activity, and increases apoptosis in human fibroblast culture, in
      vitro. The purpose of this study is the in vivo evaluation of the resterilized
      mesh repairs of abdominal hernia defects in rat models of incisional hernia by
      comparing primer repair and original mesh repairs. The rats (n = 22) were
      separated into three groups. While the abdominal defect was repaired by primary
      suture in the control group (CG), the defects were repaired by original mesh (OG)
      or resterilized mesh (RG) in mesh-repaired groups. After 21 days, the rats were
      evaluated for tissue tensile strengths, tissue hydroxyproline levels, tissue
      inflammation, fibrosis, and apoptosis. Although the tensile strengths in OG and
      RG were significantly higher than those of CG (p < .05 and p < .05), there was no
      significant difference between two groups. The tissue hydroxyproline levels in OG
      and RG were also higher than those of CG. The difference was not significant
      between the two groups. The inflammation and fibrosis indexes in OG and RG were
      significantly higher than those of CG (p < .0001 for both), but there was no
      difference between groups. While the apoptosis index in OG and RG was also higher
      than that of CG (p < .0001 for both), there was no significant difference between
      OG and RG. The usage of resterilized mesh in abdominal wall repair did not reduce
      the tissue tensile strength, did not affect the tissue hydroxyproline levels, did
      not decrease the fibrosis, and did not increase the tissue inflammation and
      apoptosis. In conclusion, usage of resterilized meshes in abdominal wall defects
      was as safe as sterilized meshes.

PMID- 18615314
TI  - The effects of duration of CO2 pneumoperitoneum on colonic anastomosis.
AB  - The aim of this study is to evaluate the effects of duration of carbon dioxide
      (CO(2)) pneumoperitoneum on experimental colonic anastomosis. Forty-eight male
      Sprague-Dawley rats were used. The rats were divided into three groups. The rats
      in group 1 (n = 16) underwent laparotomy and colonic anastomosis without
      pneumoperitoneum. The rats in group 2 (n = 16) and group 3 (n = 16) were
      subjected to 2 and 4 hours of 12 mm Hg pneumoperitoneum, respectively, before
      laparotomy and colonic anastomosis. Half of the rats were sacrified on the third
      postoperative day; and the other half, on the seventh postoperative day. A
      colonic segment including anastomosis site was resected for histopathologic and
      biochemical evaluation. On day 3, hydroxyproline levels of the three groups were
      similar. The edema score of group 2 was significantly higher than that of group
      1, and the necrosis score was higher in group 2 than in group 3. The scores of
      the other histopathologic parameters were similar. On day 7, group 3 showed
      significantly higher hydroxyproline levels than group 1, and group 1 showed a
      higher necrosis score than group 3. In conclusion, CO(2) pneumoperitoneum of 12
      mm Hg for 2 and 4 hours did not result in impaired healing of experimental
      colonic anastomosis.

PMID- 18615315
TI  - Nitric oxide administration restores the hepatic artery buffer response during
      porcine endotoxemia.
AB  - The hepatic artery buffer response, which is lost during endotoxemia, plays a
      central role in the autoregulation of liver perfusion. A temporarily decreased
      synthesis of nitric oxide during early endotoxemia might be responsible for this
      dysfunction; hence exogenous administration of nitric oxide could reestablish the
      autoregulation of hepatic blood flow and help prevent hepatic damage later in
      septic shock. Fifteen pigs were treated with lipopolysaccharide +/- the nitric
      oxide donor nitroprusside-sodium via the portal vein. Hemodynamics were measured,
      and serum chemistry and liver biopsies for nitric oxide synthase expression were
      obtained. Lipopolysaccharide decreased arterial liver perfusion after 5 hours by
      38% (p = .012), which was reversed by addition of nitroprusside (8%).
      Administration of nitroprusside preserved an increase of 28% in hepatic arterial
      upon portal vein flow reduction (p < .001). Nitroprusside maintained mRNA levels
      of constitutive nitric oxide synthase in liver tissue which were decreased by
      lipopolysaccharide (p = .026 vs. p = .114) and tempered the burst in inducible
      nitric oxide synthase expression at t = 3 hours. The early administration of the
      nitric oxide donor sodium nitroprusside during endotoxemia is able to reestablish
      the autoregulatory response of the hepatic artery following reduction of hepatic
      blood flow. This beneficial effect might help to prevent subsequent hepatic
      damage in the course of abdominal sepsis.

PMID- 18615316
TI  - The effects of hyperbaric oxygen therapy on colonic anastomosis in rats with
      peritonitis.
AB  - The aim of this study is to investigate the healing effect of hyperbaric oxygen
      (HBO) on colonic anastomoses in the presence of experimentally induced
      peritonitis. Thirty-two rats were allocated randomly into short-term anastomosis
      (STA), short-term anastomosis + HBO treatment (STA+HBO), long-term anastomosis
      (LTA), and long-term anastomosis + HBO (LTA+HBO) treatment groups. The STA and
      LTA groups were administered fluid resuscitation and antibiotics for 3 and 7
      days, respectively, whereas the HBO treatment groups received additional HBO
      therapy for 3 and 7 days, respectively. The rats were reoperated on the third and
      the seventh days of anostomoses for evaluation. The bursting pressures in STA+HBO
      and LTA+HBO therapy groups were significantly higher than those in groups with
      anastomoses alone (p < .001 and p < .01). HBO therapy did not affect the fibrotic
      index neither in STA nor in LTA groups (p > .05 for both); however, it was
      significantly higher in LTA+HBO group than that in STA+HBO group (p < .05). The
      hydroxyproline level was significantly higher in LTA group than in STA group (p <
      .05), yet HBO therapy did not affect the hydroxyproline levels in STA or LTA
      groups (p > .05 for both). It is concluded that hyperbaric oxygen treatment has
      positive effects on colonic anastomotic healing in case of peritonitis.

PMID- 18615317
TI  - Cyclosporin A-induced lipid and protein oxidation in human B-cells and in Epstein
      Barr virus-infected B-cells is prevented by antioxidants.
AB  - The incidence of post-transplant lymphoproliferative disorder (PTLD) has
      increased since cyclosporin A (CsA) became the mainstay of transplant
      immunosuppression. We have previously shown that, in addition to its potent
      immunosuppressive property, CsA-induced oxidative stress plays an important role
      in Epstein-Barr virus (EBV)-related PTLD. Using lipid hydroperoxide and
      malondialdehyde as markers of lipid oxidation, and protein carbonyls as markers
      of protein oxidation, we further investigated the in vitro effect of CsA on human
      B cells and EBV-infected human B cells. We found that CsA at 500 ng/ml, a
      relatively safe and effective blood concentration in organ transplant recipients,
      induced the highest lipid hydroperoxide and malondialdehyde after 10 min of
      treatment in time- and concentration-related kinetic studies. We also found that
      treatment with CsA at 500 ng/ml for 10 min increased the EBV-infected B cell
      protein carbonyl formation as assayed by immunoblot method. CsA-induced lipid and
      protein oxidation could be inhibited by vitamin E, N-acetyl cysteine, and
      pyrollidine dithiocarbamate. CsA significantly promoted the EBV-B cell
      transformation as assayed by colony counting, cell counting, and (3)H-thymidine
      incorporation. Our recent study provides further evidence to support the
      hypothesis that CsA exerts direct oxidative stress in EBV-infected as well as non
      EBV-infected human B cells. A greater understanding of these cellular and
      molecular mechanisms may benefit the clinical practice and prevention of PTLD.

PMID- 18615318
TI  - Ischemic preconditioning to prevent lethal ischemic spinal cord injury in a swine
      model.
AB  - OBJECTIVE: Paraplegia is a serious complication of thoracic and thoracoabdominal
      aortic operations and is the result of ischemic spinal cord injury induced by low
      perfusion pressure during cross-clamping of the aorta. Ischemic preconditioning
      (IPC) of the heart or brain with reversible sublethal ischemic injury induces
      resistance to subsequent lethal ischemia. The aim of this study is to investigate
      whether ischemic tolerance can be induced by IPC of the spinal cord in a swine
      model. STUDY DESIGN: The animals were randomly divided into three groups: the
      sham group (n = 3), control group (n = 6) and IPC group (n = 8). In the sham
      group, we performed a left thoracotomy without any ischemic injury. In the IPC
      group, the swine received a reversible ischemic spinal cord injury by aortic
      clamping for 20 min, whereas in the control group, no aortic cross-clamping was
      performed. Forty-eight hours later, the animals in both the IPC and control
      groups underwent aortic clamping for 30 min. Neurological examination was done 24
      h later, and then the animals were euthanized for histopathology and a
      malonedialdehyde spectrophotometry assay of the spinal cord tissue. RESULTS: A
      statistically significant difference in neurological outcome was observed between
      the control and IPC groups at 24 h after ischemic injury. The incidence of
      paraplegia and severe paresis was 100% in the control group and 62.5% in the IPC
      group (p = .028). Between control and IPC groups, there was no statistically
      significant difference in histopathology and only a borderline statistical
      difference in the malonedialdehyde assay of the ischemic spinal cord (p = .0745).
      CONCLUSION: In this study, IPC induced protection against a 30-min ischemic
      insult of the spinal cord, although complete recovery was not achieved (standing
      up or walking). We expect that combining this IPC with other existing protective
      methods might lead to a synergistic effect, which warrants further investigation.

PMID- 18615319
TI  - Protein kinases in organ ischemia and reperfusion.
AB  - There is ample evidence of the role that protein kinases play in the signaling
      pathways secondary to ischemia and reperfusion (I/R). The protein kinases
      initiate several interconnected downstream cascades regulated by phosphorylation
      and dephosphorylation reactions. The signaling transduction pathways ultimately
      initiate the nuclear transcription of the inflammatory and anti-inflammatory
      genes to repair and assist in the recovery of damaged cells. Although some of the
      I/R mechanisms are well identified, there is still a lack of general application
      of this knowledge in clinical practice and particularly in the role that their
      induction or inhibition can play in disease treatment or improving illness
      management. This is a review of the current understanding of the role that
      protein kinases play in the phosphoregulatory mechanisms, which mediate the
      complex processes of signal transduction secondary to organ I/R injury. Under
      ischemic conditions, diverse families of protein kinases, including tyrosine
      kinases, receptor serine kinases, and mitogen-activated protein (MAP) kinases,
      catalyze the phosphorylation of several proteins that initiate the cascade of
      events regulated by phosphorylation reactions and subsequent inflammatory gene
      expression. This phosphorylation catalyzed by protein kinases can nevertheless be
      reversed by a second group of enzymes, called protein phosphatases, which remove
      the phosphate and in that way modulate the activity of the protein kinases. The
      potential role that protein kinase inhibitors play is discussed on the basis of a
      new understanding of the mechanisms modulating phosphoregulated pathways.

PMID- 18615320
TI  - Religiosity as a protective factor against the use of drugs.
AB  - Although many studies have suggested that risk and protective factors are related
      to the use of drugs, their role has not been given due importance. More attention
      to protective factors could make them a fundamental tool in prevention programs.
      Since low socioeconomic level and adolescence are known as risk factors, the aim
      of this study was to identify which factors would prevent Brazilian adolescents
      from low-income families from using drugs. A qualitative method and an
      intentional sample selected by criteria were adopted for this investigation.
      During 2003, sixty-two youngsters, ages 16 to 24 years old, 30 drug users, and 32
      nonusers were administered a semistructured interview. The subjects perceived
      family and religiosity as important protective factors in their lives. With
      regard to religiosity, 81% of nonusers believed in and practiced a religion,
      whereas only 13% of users considered themselves as being religious. The belief in
      and practice of a religion were also more evident among family members of
      nonusers (74%) than those of users (33%). These results indicated that religion
      may be a relevant protective factor for the sample studied, helping the family
      unit in keeping youth away from drugs. The study's limitations were noted.

PMID- 18615321
TI  - Effectiveness of an outreach treatment program for inner city crack abusers:
      compliance, outcome, and client satisfaction.
AB  - In a randomized controlled trial the effectiveness of an outreach treatment
      program (OTP) was compared with standard addiction care services for hard-drug
      addicts in Rotterdam (The Netherlands). The study aimed at chronic, high-risk
      crack abusers who were insufficiently engaged in standard addiction treatment
      services. Data were collected from February 2000 to December 2001. A total of 124
      subjects participated in the study at baseline. Follow-up data were available for
      94 subjects. Outcome measures included treatment compliance, outcome, and
      satisfaction. Data were collected by means of monthly registrations, EuropAsi
      interviews and an evaluation form. There was a high compliance with OTP in the
      treatment group; the average length-of-stay was 6 months, with visits three times
      a week. Although both groups were well represented in standard care,
      participation was mainly based on methadone maintenance. Subjects treated in OTP
      showed significant improvements in physical health, general living conditions,
      and psychiatric status, but no change in employment, substance abuse, and legal
      status. The control group remained almost unchanged. Clients of OTP reported
      feeling very satisfied with their treatment. On-the-spot incentives and a
      positive relationship with the care provider were directly associated with
      treatment retention. An outreach treatment program, as conducted in this study,
      is associated with high compliance, general improvement, and treatment
      satisfaction. Characteristics of this treatment modality are (1) assertive
      outreach, (2) a mixed program with incentives, and (3) a strong focus on
      individual-bound therapy. Further research is needed with larger groups and
      similar conditions at baseline assessment.

PMID- 18615322
TI  - Amelogenesis imperfecta - a systematic literature review of associated dental and
      oro-facial abnormalities and their impact on patients.
AB  - OBJECTIVE: Amelogenesis imperfecta (AI) is a disease primarily affecting
      amelogenesis, but other aberrations have been reported. The purposes of this
      review were: (1) to identify other anomalies associated with AI, and (2) to
      describe the impact of the disease and its associated conditions on the oral
      health-related quality of life of patients, and the economic consequences.
      MATERIAL AND METHODS: A literature search was conducted in the following
      databases: PubMed, EMBASE, Bibliotek.dk, The Cochrane Library, Web of Science,
      and OMIM, supplemented by a search for selected authors. Based on titles and
      abstracts, 137 papers were identified. RESULTS: Most articles were case reports
      or case series with few cases. Aberrations were reported in the eruption process,
      in the morphology of the crown, in the pulp-dentine organ, and in the number of
      teeth. Gingival conditions and oral hygiene were usually reported to be poor, and
      calculus was a common finding. Open bite was the most commonly reported
      malocclusion. A negative impact on patients' oral health-related quality of life
      was described, but information was scarce. No information was found on the
      economic impact. CONCLUSIONS: A number of aberrations associated with AI have
      been reported, but not sufficiently systematic to allow for a secondary analysis
      and synthesis of the findings. The impact on patients in terms of reduced quality
      of life and economic burden needs to be studied.

PMID- 18615323
TI  - Opalescence and fluorescence properties of indirect and direct resin materials.
AB  - OBJECTIVE: To measure the opalescence and fluorescence properties of indirect and
      direct resin materials before and after polymerization, and to determine the
      influence of the material and shade group combination on these properties.
      MATERIAL AND METHODS: BelleGlass NG (BG, indirect resin) and Estelite Sigma (ES,
      direct resin), each composed in 3 shade groups (EN, OD and TL for BG; BS, AS and
      OP for ES) out of a total of 16 shades were investigated. Resin material was
      packed into a mold (the BEC condition) and polymerized with a light
      polymerization unit (CWL). Secondary polymerization (CIC) was performed for BG.
      Color was measured in the BEC, CWL, and CIC conditions, and the opalescence
      parameter (OP) and fluorescence parameter (FL) were calculated. RESULTS: For the
      OP, the mean for BG material was 24.3 before polymerization, which changed to
      19.9 after polymerization (CIC). In the case of ES, the mean OP before
      polymerization was 25.6, which changed to 12.4 after polymerization (CWL). For
      the FL, the mean FL for BG was 2.5 before polymerization, which changed to 0.7
      after polymerization. In the case of ES, the mean FL before polymerization was
      1.2, which did not change after polymerization. Material and shade group
      combination influenced the OP and FL values (p<0.05). CONCLUSIONS: The
      opalescence and fluorescence properties of resin materials varied depending on
      the material, shade group, and polymerization. Clinically, these properties
      should be considered when neighboring teeth are restored with different types of
      material.

PMID- 18615324
TI  - Characteristics of collagenase-2 from gingival crevicular fluid and peri-implant
      sulcular fluid in periodontitis and peri-implantitis patients: pilot study.
AB  - OBJECTIVE: To compare collagenase activity and collagenolytic matrix
      metalloproteinase (MMP) levels in gingival crevicular fluid (GCF) and in peri
      implant sulcular fluid (PISF) in gingivitis (G), chronic periodontitis (CP), and
      peri-implantitis (PI) human subjects. MATERIAL AND METHODS: GCF and PISF were
      collected on filter paper strips, volume was determined, and samples were
      extracted in buffer containing general proteinase but not MMP inhibitors.
      Collagenase activity was measured using a DNP-synthetic octapeptide, and
      molecular and activation forms of collagenase-2 by Western immunoblotting.
      RESULTS: GCF from CP and G sites exhibited elevated collagenase activity and
      flow, but collagenase concentrations expressed per microl were not significantly
      different between the healthy and G sites. Minimal fluid was obtained from
      healthy PISF, and collagenase concentration was the same or lower than in healthy
      GCF. Although PISF flow was 34% lower than GCF flow in CP subjects, collagenase
      concentration in CP and in PI sites was 78% and 971% greater, respectively, than
      in the appropriate healthy sites. Western immunoblot revealed MMP-8 in both PISF
      and GCF; fibroblast-type MMP-8 was not detected in healthy GCF and PISF.
      Immunoreactivity level and inactive and activated forms of PMN-type MMP-8 in GCF
      and PISF increased with the severity of periodontitis and peri-implantitis.
      Enhanced levels of fibroblast-type MMP-8 in active form were detected only in
      severe CP GCF and PI PISF. CONCLUSIONS: Peri-implantitis PISF contained higher
      collagenase-2 levels and activity than GCF from similar deep CP sites. GCF and
      PISF from severe CP and PI exhibited the highest activation of MMP-8 isoenzymes
      species (PMN and fibroblast-type).

PMID- 18615325
TI  - Shear bond strength of one etch-and-rinse and five self-etching dental adhesives
      when used by six operators.
AB  - OBJECTIVE: To test the hypothesis that some single-bottle self-etching adhesives
      bond as well to enamel and dentin as a typical two-bottle etch-and-rinse
      adhesive. MATERIAL AND METHODS: Six operators used one two-bottle etch-and-rinse
      dentin adhesive (Scotchbond MP) and five all-in-one self-etching adhesives (iBond
      Gluma Inside, Clearfil S(3) Bond, iBond Experimental, Xeno IV, and G-BOND). Each
      operator carried out six bondings to enamel and six bondings to dentin with each
      adhesive. After 24 h of storage in water at 37 degrees C, bond strength was
      determined in shear. RESULTS: The pooled results of all the adhesives revealed no
      significant difference (p>0.05) in bond strength between dentin and enamel.
      However, there were significant differences (p<0.0001) between the different
      adhesives. The etch-and-rinse adhesive did better than the self-etching adhesives
      when substrate was not an issue (pooled enamel and dentin results). On comparing
      the performance of the different adhesives, it became clear that there were
      significant interactions (p<0.0001) between substrates and products. There were
      also significant differences (p<0.0001) between operators, and the interaction
      between operators and products was significant (p<0.0002). CONCLUSIONS: The
      tested etch-and-rinse adhesive did better than the tested self-etching adhesives.
      The shear bond strength results were also strongly affected by the operator as
      well as by the interaction between operator and used product. The pooled bond
      strength values of the different adhesives revealed no difference in bond
      strength to dentin versus enamel.

PMID- 18615326
TI  - Irreversible ototoxicity associated with the use of erlotinib in a patient with
      pancreatic cancer.

PMID- 18615327
TI  - Effects of eccentric rotation on the human pitch vestibulo-ocular reflex.
AB  - CONCLUSION: The pitch plane vestibulo-ocular reflex (VOR) gain and symmetry at
      low frequencies (< or =0.3 Hz) are enhanced by otoliths and/or somatosensory
      sensory cues during combined angular and linear stimuli. We conclude that neural
      processing of these linear motion cues is used to improve the VOR when stimulus
      frequencies are below the optimal range for the canals. OBJECTIVE: The purpose of
      this study was to examine the effects of eccentric rotation on the passive pitch
      VOR responses in humans. SUBJECTS AND METHODS: Eleven subjects were placed on
      their left sides (90 degrees roll position) and rotated in the pitch plane about
      an earth-vertical axis at 0.13, 0.3, and 0.56 Hz. The inter-aural axis was either
      aligned with the axis of rotation (no modulation of linear acceleration) or
      offset from it by 50 cm (centripetal linear acceleration directed feet-ward). The
      modulation of pitch VOR responses was measured in the dark with a binocular
      videography system. RESULTS: The pitch VOR gain was significantly increased and
      the VOR asymmetry was significantly reduced at the lowest stimulus frequencies
      during eccentric rotation. There was no effect of eccentric rotation on the pitch
      gain or asymmetry at the highest frequency tested.

PMID- 18615328
TI  - Effect of inner ear blood flow changes in Meniere's model mice.
AB  - CONCLUSIONS: The endolymphatic sac (ES) is important for inner ear fluid
      homeostasis. A dysfunctional ES can cause vertigo attacks following additional
      stress such as a sudden change in endolymphatic volume and/or pressure, or
      restricted inner ear blood flow. OBJECTIVE: The purpose of this study was to
      elucidate the mechanism of vertigo attacks in Meniere's disease. MATERIALS AND
      METHODS: Adult CBA/J mice were given an intratympanic injection of
      lipopolysaccharide and an intraperitoneal injection of aldosterone. These 'model'
      animals had epinephrine or sodium nitroprusside (SNP) instilled into the middle
      ear cavity. Cochleae, vestibules, and endolymphatic sacs were studied
      morphologically by light microscopy. RESULTS: The injection of epinephrine into
      the model animals reduced the endolymphatic hydrops in the cochlea, but also
      produced mild hydrops in the vestibule, which was never observed in untreated
      (control) animals. The ES did not react to epinephrine in the normal way.
      Injection of SNP did not cause any changes.

PMID- 18615329
TI  - Increased expression of p63 and survivin in cholesteatomas.
AB  - CONCLUSION: This study showed increased expression of p63 and survivin in
      cholesteatoma. Our finding indicates a putative role of p63 and survivin in the
      development of certain cholesteatomas. OBJECTIVES: Keratinocytes in cholesteatoma
      demonstrate uncoordinated hyperproliferation, migration, and invasion properties.
      p63 is a p53 homologue and a marker expressed in replicating keratinocytes.
      Survivin is an inhibitor of apoptosis protein that is abundantly expressed in
      most solid and hematologic malignancies. The purpose of this study was to
      investigate the differential expression of p63 and survivin in human middle ear
      cholesteatoma epithelium. MATERIALS AND METHODS: The expression levels of p63 and
      survivin protein were examined by immunohistochemical analysis of 40
      cholesteatomas and 5 skin tissues obtained from patients during ear surgery.
      RESULTS: Expression of p63 protein was diffusely observed in entire samples of
      cholesteatoma, especially in acquired cholesteatoma, compared with the control
      group. Congenital cholesteatoma showed variable p63 reactivity in a basal cell
      like pattern. Primary and recurrent cholesteatomas showed no significant
      difference in p63 expression. Survivin was detected in 31 of 40 cholesteatoma
      samples. Acquired cholesteatomas showed especially increased survivin expression
      compared with congenital cases. The expression of p63 was correlated with
      survivin expression.

PMID- 18615330
TI  - MASPIN tumour-suppressing activity in head and neck squamous cell carcinoma:
      emerging evidence and therapeutic perspectives.
AB  - CONCLUSIONS: A large series confirmation may suggest elective neck dissection in
      cN0 MASPIN-negative oral squamous cell carcinomas (SCCs). Re-activated nuclear
      MASPIN in association with anti-angiogenic or cytotoxic drugs may be extremely
      effective in the treatment of laryngeal SCC. OBJECTIVES: MASPIN is a serpin
      showing a unique tumour-suppressing activity. Despite the significant incidence
      of head and neck SCC (HNSCC), a limited number of studies has considered MASPIN's
      role in these malignancies. This review focuses on the attempts to translate
      MASPIN's HNSCC suppressive properties toward a diagnostic/prognostic tool and a
      novel carcinoma therapy. METHODS: A systematic literature review was performed to
      investigate available evidence about MASPIN subcellular localization and
      biological role in HNSCC. RESULTS: Five studies have investigated MASPIN's
      expression in oral SCC. Most of them concluded that low or absent MASPIN
      cytoplasmic expression was more frequent in oral carcinomas with lymph node
      metastases. Only our group evaluated MASPIN's role in laryngeal SCC. Higher
      nuclear MASPIN expression was found in patients without SCC recurrence and was
      significantly associated with longer disease-free survival. Micro-vascular
      density was lower in laryngeal carcinomas with MASPIN nuclear staining. The
      relation between MASPIN and M30-assessed apoptosis in laryngeal SCC supports the
      hypothesis of an important apoptosis-sensitizing effect of nuclear MASPIN.

PMID- 18615331
TI  - Effects of semicircular canal electrode implantation on hearing in chinchillas.
AB  - CONCLUSION: Implantation of vestibular prosthesis electrodes in chinchilla
      semicircular canal ampullae can be accomplished without significant loss of
      cochlear function; however, the risk of hearing loss with the current surgical
      technique is high. OBJECTIVES: To determine if it is possible to implant
      vestibular prosthesis electrodes into the labyrinth without damaging hearing, and
      to quantify the extent of hearing loss due to implantation. MATERIALS AND
      METHODS: The left semicircular canals of six chinchillas were implanted with
      three bipolar pairs of electrodes using a transmastoid approach. Right ears,
      which served as controls, were subjected to the same mastoid approach without
      fenestration and implantation. Auditory brainstem response hearing thresholds to
      free-field clicks and tone pips at 2, 4, 6, and 8 kHz were measured bilaterally 3
      9 weeks after implantation. Hearing thresholds were compared between sides and
      against data from six normal chinchillas. RESULTS: Four implanted ears suffered
      severe hearing loss, with thresholds ranging from 5 to 11 SD above the mean
      threshold of sham surgery control ears across all tested stimuli. Two implanted
      ears had preserved hearing, with thresholds remaining within 1 SD of the mean
      threshold of sham surgery control ears across nearly all stimulus frequencies.

PMID- 18615332
TI  - Comparable efficacy and tolerability between twice daily and three times daily
      betahistine for Meniere's disease.
AB  - CONCLUSION: Betahistine at oral doses of 16 mg tid and 24 mg bid provides similar
      efficacy and tolerability in the treatment of vertigo in patients with Meniere's
      disease. OBJECTIVE: To compare the efficacy and tolerability of betahistine 16 mg
      tid and 24 mg bid in the treatment of vertigo in patients with Meniere's disease.
      PATIENTS AND METHODS: This was a randomized, open-label study of 120 consecutive
      patients with well-established Meniere's disease treated with betahistine 16 mg
      tid or 24 mg bid for 24 weeks. Treatment efficacy, assessed by clinical outcome
      level in terms of severity, frequency and duration of vertigo spells, was
      evaluated at baseline and at weeks 4, 12 and 24. Between-group comparisons of
      outcome data (Wilcoxon, Mann-Whitney U test) and adverse events (chi-squared
      test) were made. RESULTS: Betahistine 16 mg tid or 24 mg bid showed a significant
      improvement in clinical outcome level from baseline to week 24 (p < 0.01). There
      was no significant difference between dosage groups regarding improvement in
      vertigo at any time point during the study. There was no significant difference
      between groups in the incidence of adverse events, which was low (maximum:
      headache, 16 mg tid, 16.7% of patients at week 4; 6.7% at week 24). The number of
      patients reporting adverse events diminished with time.

PMID- 18615333
TI  - Expression of PTEN and phosphorylated Akt in human cholesteatoma epithelium.
AB  - CONCLUSION: We found a reduced PTEN and an increased phosphorylated Akt (p-Akt)
      expression in cholesteatoma epithelium when compared with retro-auricular (RA)
      skin. The negative correlation between cholesteatoma PTEN and p-Akt may suggest
      that cellular survival mechanisms may be involved in cholesteatoma epithelial
      hyperplasia. OBJECTIVES: The tumor suppressor PTEN regulates the
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and modulates cell
      cycle progression and cell survival. We hypothesized that PTEN might be involved
      in this pathway mechanism in cholesteatoma. MATERIALS AND METHODS: Western
      blotting and immunohistochemistry were used to examine the expression of PTEN and
      p-Akt in 16 cases of cholesteatoma and paired cases of RA skin. RESULTS: In
      cholesteatoma, p-Akt expression was significantly higher than in RA skin, whereas
      PTEN expression was significantly lower in cholesteatoma when compared with skin
      (p < 0.05). Immunohistochemical analysis showed that weak PTEN immunoreactivity
      was observed in the nuclei of cholesteatoma epithelium, whereas strong PTEN
      immunoreactivity was detected in the nuclei of skin. Also, strong p-Akt
      immunoreactivity was observed in the cytoplasm of cholesteatoma epithelium,
      whereas very weak or no p-Akt immunoreactivity was observed in the RA skin.
      Furthermore, we found that a significant inverse correlation exists between PTEN
      and p-Akt expression (r = -0.796).

PMID- 18615334
TI  - Hypertonic saline injections to enhance the radiofrequency thermal ablation
      effect in the treatment of base of tongue in obstructive sleep apnoea patients: a
      pilot study.
AB  - CONCLUSION: Hypertonic saline (HS) infiltration in the base of the tongue (BOT)
      in multilevel radiofrequency ablation (RFA) treatment was followed by significant
      acute complications in terms of soft tissue swelling. Three patients were defined
      as cured. No significant changes in the measured parameters were encountered,
      although, several of them showed a clear trend. New treatment modalities are
      needed to keep multilevel RFA treatment as a minimally invasive procedure.
      OBJECTIVES: To assess the efficacy and morbidity of RFA of the soft palate (SP)
      and BOT infiltrated with HS in obstructive sleep apnoea in a prospective, non
      randomized clinical study. PATIENTS AND METHODS: The inclusion criteria were age
      between 30 and 65 years, habitual snoring and excessive daytime sleepiness, a
      body mass index < or =33, and an apnoea-hypopnoea index > or =20. RFA of the SP
      and the BOT was delivered under local anaesthesia. HS solution was injected
      before the treatment into the BOT. The morbidity of the procedure was assessed
      with a visual analogue scale, and efficacy by separate questionnaires and sleep
      registration. The volume changes induced by the procedure were evaluated with
      cephalometric radiographs (CRs). RESULTS: Twelve males and one female with a
      median age of 50 years (range 41-62) entered the study. Six patients (46%) had
      more postoperative swelling in the upper airway than expected. Three patients
      were defined as cured. The trend in the questionnaires was clear, but not
      significant. In the soft tissue airway CR measurements no significant changes
      were encountered, although a trend towards volume reduction was seen in the
      posterior airway space measure.

PMID- 18615335
TI  - Differential diagnosis between osteomyelitis and bone tumors.
AB  - BACKGROUND: Hematogenous osteomyelitis is often difficult to distinguish from a
      bone tumor because clinical findings are noncontributory and radiological
      features can mimic a bone tumor. Recently, the penumbra sign, a higher signal
      intensity feature of the thin layer of granulation tissue which lines the abscess
      cavity on T1-weighted magnetic resonance (MR) images, has been reported to be
      helpful for discriminating subacute osteomyelitis. PURPOSE: To determine helpful
      findings for distinguishing osteomyelitis from bone tumors. MATERIAL AND METHODS:
      The laboratory and imaging findings of a consecutive series of 244 patients
      referred to our institution with a suspected bone tumor were reviewed. There were
      15 cases of osteomyelitis, 160 bone tumors, and 69 tumor-like lesions. RESULTS:
      In osteomyelitis, the C-reactive protein (CRP) level increased in nine patients
      and the penumbra sign was seen in 11 patients. In bone tumors and tumor-like
      lesions, a high CRP level was observed in 21 patients and the penumbra sign was
      seen in two patients. The sensitivity of the penumbra sign for osteomyelitis was
      73.3%, with a specificity of 99.1%. CONCLUSION: The penumbra sign and a high CRP
      level support the diagnosis of osteomyelitis and may help to exclude the presence
      of a tumor.

PMID- 18615336
TI  - Quantitative renal cortical perfusion in human subjects with magnetic resonance
      imaging using iron-oxide nanoparticles: influence of T1 shortening.
AB  - BACKGROUND: Using conventional contrast agents, the technique of quantitative
      perfusion by observing the transport of a bolus with magnetic resonance imaging
      (MRI) is limited to the brain due to extravascular leakage. PURPOSE: To perform
      quantitative perfusion measurements in humans with an intravascular contrast
      agent, and to estimate the influence of the T1 relaxivity of the contrast agent
      on the first-pass response. MATERIAL AND METHODS: Renal cortical perfusion was
      measured quantitatively in six patients with unilateral renal artery stenosis
      using a rapid gradient double-echo sequence in combination with an intravenous
      bolus injection of NC100150 Injection, an intravascular contrast agent based on
      iron-oxide nanoparticles. The influence of T1 relaxivity was measured by
      comparing perfusion results based on single- and double-echo data. RESULTS: The
      mean values of cortical blood flow, cortical blood volume, and mean transit time
      in the normal kidneys were measured to 339+/-60 ml/min/100 g, 41+/-8 ml/100 g,
      and 7.3+/-1.0 s, respectively, based on double-echo data. The corresponding
      results based on single-echo data, which are not compensated for the T1
      relaxivity, were 254+/-47 ml/min/100 g, 27+/-3 ml/100 g, and 6+/-1.2 s,
      respectively. CONCLUSION: The use of a double-echo sequence enabled elimination
      of confounding T1 effects and consequent systematic underestimation of the
      perfusion.

PMID- 18615337
TI  - Triple A syndrome mimicking ALS.
AB  - We report a 22-year-old female who presented with distal muscular atrophy and
      weakness in all limbs for two years. Reflexes were symmetrically brisk and
      electrodiagnostic studies were consistent with upper and lower motor neuron
      involvement. A diagnosis of juvenile ALS was considered. However, surgery for
      achalasia in childhood and identification of alacrima and adrenal insufficiency
      suggested Triple A syndrome accompanied by neurological symptoms. Sequencing of
      the AAAS gene identified compound heterozygous mutations confirming the clinical
      diagnosis and demonstrating that Triple A syndrome can mimic juvenile ALS.

PMID- 18615338
TI  - Enteral and parenteral nutrition in the later stages of ALS: an observational
      study.
AB  - Current practice guidelines state that enteral feeding should be proposed and
      provided whenever ALS patients show significant dysphagia and/or weight loss.
      Percutaneous endoscopic gastrostomy (PEG) is usually available at ALS centres,
      but this method is not indicated in the case of patients with severe respiratory
      impairment. We undertook a study to assess the feasibility of applying home
      parenteral nutrition (PN) to ALS patients with respiratory insufficiency, to
      assess the complications and survival times after the procedure. PN was provided,
      via an implanted port, to 30 ALS patients with respiratory insufficiency
      requiring nutritional support. Nutritional and neurological follow-up were
      carried out. The results were compared with those obtained on a group of 35
      patients who underwent PEG, who were subdivided into patients with respiratory
      insufficiency and those without respiratory insufficiency at the time of the PEG.
      Post-procedure survival of PEG patients with respiratory insufficiency was
      similar to those of the PN group. The results of the study suggest that PN is a
      safe and effective method, which improves the patients' nutritional status and
      stabilizes their weight in most cases. Home PN could be applied to patients with
      advanced ALS and poor respiratory function as an alternative to enteral feeding.

PMID- 18615339
TI  - The epidemiology of amyotrophic lateral sclerosis in Reggio Emilia, Italy.
AB  - Incidence and mortality rates of amyotrophic lateral sclerosis (ALS) vary between
      countries, and in some studies appear to increase over time. We performed a study
      to assess ALS incidence in a northern Italy area over a 10-year period. We
      identified the new cases of probable or definite ALS diagnosed among residents in
      Reggio Emilia province between 1996 and 2005 using several sources of data, such
      as death certificates, clinical records, hospital discharge registers and drug
      prescriptions. A total of 94 newly-diagnosed patients were identified. The
      average standardized incidence in the period was 2.0 and 1.0 cases/100,000/year,
      using the Italian and the world population, respectively, as reference. There was
      no variation in rates over time. Incidence was 1.3 in males and 0.8 in females.
      No cases were observed in patients under 35 years of age. Incidence increased
      after the age of 55 years, reaching a peak in the group aged 70-74 years and
      declining thereafter. We concluded that ALS incidence in this population was
      similar to that observed in other Italian regions and European countries, and no
      variation was identified during the study period.

PMID- 18615340
TI  - Birthplace predicts risk for prehospital sudden cardiac death in middle-aged men
      who migrated to metropolitan area: The Helsinki Sudden Death Study.
AB  - BACKGROUND: Eastern-born male Finns, irrespective of their place of residence,
      have high mortality from coronary heart disease (CHD), and half of such deaths
      are sudden. AIM: To study whether eastern birthplace alone or combined with life
      style factors predicts risk for prehospital sudden cardiac death (SCD) in the new
      (west) low-mortality area of residence. METHOD: Prospective case-control autopsy
      study of all (700) out-of-hospital deaths of men aged 35-69 years in metropolitan
      Helsinki during 1981-82 and 1991-92. Data on CHD risk factors were obtained for
      405, of whom 149 died of SCD (cases) and 256 of other causes (controls). RESULTS:
      A birthplace-by-age interaction with SCD (P=0.024) and with myocardial infarction
      (P=0.005) appeared. Men < or =54 years born in the east were more often victims
      of SCD (odds ratio 2.99, 95% confidence interval 1.38-6.49, P=0.006) than were
      men born in the west, independently of CHD risk factors. SCD was predicted also
      by alcohol consumption, age, smoking, and hypertension. Amongst older (>54 years)
      men no association with birthplace was any longer evident, but alcohol and socio
      economic status predicted SCD. CONCLUSIONS: Birthplace-based risk for SCD
      suggests the contribution of early life environment or genetic east-west
      differences, reflecting Finns' two-phase settlement history.

PMID- 18615341
TI  - A model for consultation with Aboriginal stakeholders about young people's mental
      health and wellbeing: the NSW School-Link Training Program.
AB  - OBJECTIVE: The aim of this paper is to describe a model for consultation with
      Aboriginal stakeholders used in the development of a training course, by the NSW
      Institute of Psychiatry, about young people's mental health and wellbeing.
      Historical, social and political factors contribute to the elevated rates of
      mental distress and disorder experienced by many Aboriginal young people.
      However, these young people often do not receive the help they need. Knowledge,
      skills and attitudes of clinicians are associated with the uptake of services.
      Therefore, a training course for clinicians was developed utilizing a detailed
      consultation process with Aboriginal stakeholders. CONCLUSIONS: The course was
      delivered as part of an ongoing comprehensive interagency training program for
      2000 clinicians. The course was positively evaluated by participants and
      stakeholders, suggesting that the course development, including the consultation
      process with Aboriginal stakeholders, was effective in meeting participant and
      stakeholder needs. Agencies may be interested in the application of this model to
      consultation processes with Aboriginal communities and with other populations.

PMID- 18615342
TI  - Expensive detour or a way forward? The experience of routine outcome measurement
      in an aged care psychiatry service.
AB  - OBJECTIVE: This paper describes and reflects upon the experience of a small,
      integrated aged care psychiatry service that has utilized the National Outcomes
      Casemix Collection (NOCC) routine outcome measurements within clinical practice,
      service management and evaluation. The goals of the NOCC initiative are reviewed
      in light of this experience. CONCLUSION: Routine outcome measurement has the
      potential to significantly improve aged care psychiatric service delivery. The
      service described has developed a model that the authors believe demonstrates the
      potential for routine outcome measures to improve the monitoring of patient
      progress, care planning, team communication, management and the understanding of
      service effectiveness - goals that are consistent with NOCC philosophy. However,
      this requires both ongoing development of infrastructure support and the
      willingness of clinicians to explore their utility.

PMID- 18615343
TI  - The employment of consumers in mental health services: politically correct
      tokenism or genuinely useful?
AB  - OBJECTIVE: The aim of this paper is to examine the role of consumers as service
      providers and to describe the successful employment of peer support workers in a
      public mental health service. CONCLUSIONS: The Peer Support Worker program in
      Adelaide, South Australia is consistent with evidence obtained from previous
      research in demonstrating the successful training and employment of consumers as
      peer workers in a public mental health service.

PMID- 18615344
TI  - The history and future prospective of haplo-identical stem cell transplantation.
AB  - Initial attempts at haplo-identical transplantation with T-cell replete bone
      marrow (BM) were associated with a high transplant-related mortality (TRM),
      mainly caused by severe graft-versus-host disease (GvHD), and previous efforts to
      prevent GvHD by ex vivo T-cell depletion of haplo-identical BM were associated
      with a high risk of graft failure and other complications. Improvements in large
      scale T-cell depletion techniques of haplo-identical peripheral mobilized stem
      cells (PBSC) have overcome the human leukocyte antigen (HLA) barrier by using
      megadose numbers of stem cells obtained by either highly purified CD34(+)
      selection or negative depletion of T cells. In addition, recent insights into the
      role of graft-facilitating and anti-leukemic alloreactive natural killer (NK)
      cells, the permanent availability of the haplo-identical donor post-transplant
      and continuous improvements in graft-engineering techniques for the generation of
      effector cells for post-transplant adoptive transfer, have facilitated the
      development of strategies to decrease regimen-related toxicity through the use of
      less intensive preparative regimens, prevent severe infections by rebuilding the
      immune system and decrease the risk of relapse by exploiting the alloreactivity
      of donor NK cells and other donor-derived effector cells.

PMID- 18615345
TI  - Treatment of chronic spinal cord injured patients with autologous bone marrow
      derived hematopoietic stem cell transplantation: 1-year follow-up.
AB  - BACKGROUND: Transplanted bone marrow (BM) cells have been found to improve
      neurologic disease in central nervous system (CNS) injury models by generating
      neural cells or myelin-producing cells. The results in treated patients and
      animal models suggest that BM cells could potentially be used as a therapy for
      spinal cord injury (SCI) patients. METHODS: Nine patients with chronic complete
      SCI with American Spinal Injury Association (ASIA) Impairment Scale (ASIA) grade
      A were included in this study. They were treated with autologous BM-derived
      hematopoietic progenitor stem cell transplantation without any serious
      complications. All patients completed the protocols successfully. RESULTS: Three
      weeks after the operation all patients' movements and sensations were improved.
      All patients had ASIA grade B or C after the operation. DISCUSSION: We used
      autologous hematopoietic progenitor stem cells in order to avoid the problems
      associated with immunologic rejection and graft-versus-host (GvH) reactions,
      which are frequently caused by allografts. The advantage of this type of cell
      therapy is that it is not associated with carcinogenesis, which sometimes occurs
      with embryogenic stem cell therapy. To evaluate the patients we used neurologic
      impairment scales (ASIA scores), pre- and post-operative Somato Sensorial Evoked
      Potential (SSEP) assessments and pre- and post-operative Magnetic Resonance
      Imaging (MRI). All the data showed that BM-derived autologous stem cell therapy
      is effective and safe for the treatment of chronic SCI.

PMID- 18615346
TI  - Effects of dextran on proliferation and osteogenic differentiation of human bone
      marrow-derived mesenchymal stromal cells.
AB  - BACKGROUND: Bioreactors have been used extensively to construct tissue-engineered
      bone. However, mass transport and flow shear stress, the two main factors
      contributing to the construction of tissue-engineered bone, cannot be studied
      separately when changing the perfusing rate. A tackifier needs to be added into
      the medium to separate the two factors. This study investigated the feasibility
      of using dextran as a tackifier in the study of individual effects of mass
      transport and flow shear stress on the construction of tissue-engineered bone.
      METHODS: Human bone marrow-derived mesenchymal stromal cells (hBMSC) were
      isolated and cultured in media containing 1%, 3%, 5%, 7% and 9% dextran
      [molecular weight (MW) 70000]. Cell proliferation and osteogenic differentiation
      were observed in vitro. hBMSC cultured without dextran provided a control group.
      RESULTS: Cell proliferation was found to have no significant statistical
      difference (P>0.05) with a dextran concentration range of 1-7%. No significant
      difference in alkaline phosphatase (ALP) activity (P>0.05) was found among the
      different groups. Alizarin red staining showed no difference in mineralized
      extracellular matrix among the groups with a concentration of dextran less than
      9%. Expression of collagen, ALP, osteopontin (OPN) and osteocalcin (OC) genes did
      not show any difference with a concentration range of 1-7%. DISCUSSION: When
      using a bioreactor to construct tissue-engineered bone, it is feasible to add a 1
      7% dextran (MW 70000) concentration into the medium in order to study the effects
      of mass transport and flow shear stress.

PMID- 18615347
TI  - Ageing, remembering, and executive function.
AB  - This study was designed to investigate the relationship between executive
      functions and the age-related decline in episodic memory through the states-of
      awareness approach. Following the presentation of a word list, a group of younger
      adults and a group of older adults undertook a recognition test in which they
      classified their responses according to the Remember-Know-Guess procedure
      (Gardiner & Richardson-Klavehn, 2000). In order to operationalise the executive
      function hypothesis, we investigated three specific executive functions
      (updating, shifting, and inhibition of a prepotent response) described in Miyake
      et al.'s (2000) theoretical model, and a complex executive task. The results
      revealed that fewer "R" responses were made during the recognition test by the
      older than the younger group, whereas there was no difference between the groups
      in the number of "K" responses. In addition, correlations indicated that
      remembering depended on executive function measures, whereas knowing did not. The
      hierarchical regression analyses showed that controlling for executive function,
      and particularly for the 2-back test, largely removed the age-related variance in
      remembering. These findings support the notion that executive dysfunction, and
      specifically updating decline, plays a central role in age-related memory loss.

PMID- 18615348
TI  - Fatal gas embolism during ureteroscopic holmium: yttrium-aluminium-garnet laser
      lithotripsy under spinal anesthesia - a case report.
AB  - Ureteroscopic holmium: yttrium-aluminium-garnet (Ho:YAG) laser lithotripsy is an
      excellent treatment modality, especially for a large impacted ureteral stone. The
      treatment is efficient and safe. It helps surgeons to carry out a minimally
      invasive lithotripsy instead of an open surgery in patients with ureteral
      calculi. Here, we present the first report of a fatal gas embolism that occurred
      during ureteroscopic Ho:YAG laser lithotripsy under spinal anesthesia. When this
      complication occurs, the correct crisis resolution protocols, such as prevention
      of further air entry, reduction in the volume of air entrained, well-hydration,
      and rapid initiation of cardiopulmonary resuscitation with administering
      inotropic drugs, are highly effective in the critical period.

PMID- 18615349
TI  - A new minimally invasive method for the transtubal, microendoscopic application
      of fluids to the middle ear.
AB  - The Eustachian (or auditory) tube is of central importance for the regulation of
      ambient air pressure changes within the middle ear spaces. Dysfunction of the
      Eustachian tube usually leads to chronic inflammatory changes of the middle ear.
      The aim of the present feasibility study was to investigate an alternative,
      minimally invasive approach for the application of fluids to the middle ear via
      the Eustachian tube. This so-called transtubal application (TTA) was conducted in
      a prospective, non-randomized study with a total of ten subjects. The TTA
      approach consisted of placing a microendoscope within the Eustachian tube under
      local anaesthesia via its epipharyngeal opening. Subsequently, fluids were
      applied through an additional working channel after microendoscopic evaluation.
      Therefore the subjects were positioned supine-laterally and had to swallow
      actively. The successful fluid application into the middle ear was evidenced by
      microendoscopy of the tympanic membrane (visualization of the fluid level). In
      all cases, a successful application could be evidenced. Side effects (e.g. pain,
      mucosal injuries, microbleedings) were not observed. This new technique (TTA)
      offers the opportunity of a minimally invasive approach to treat tubal
      dysfunction and possibly other middle ear diseases by local fluid and/or drug
      application.

PMID- 18615350
TI  - Nicotine and alcohol use in adolescent psychiatric inpatients: associations with
      diagnoses, psychosocial factors, gender and age.
AB  - The aim of the survey was to describe the proportion of smokers and alcohol users
      in a group of children and adolescents admitted to a German department of child
      and adolescent psychiatry and psychotherapy. In addition, the proportion of
      smokers in this group of patients was compared with the proportion in the general
      population of the same age. The sample was composed of all children and
      adolescent inpatients (n=432, 8-17 years old meeting inclusion criteria) admitted
      to a German department of child and adolescent psychiatry between May 2001 and
      June 2003. A shortened adaptation of the questionnaire on legal and illegal drug
      use, developed by the Swiss Professional Service for Alcohol Problems, Lausanne,
      was used. Initiation, frequency and quantity of drug use, and parental substance
      use were assessed. The results showed an association between conduct disorder
      (CD) and attention-deficit/hyperactivity disorder (ADHD) and an early initiation
      of nicotine and alcohol use. Girls and boys with CD and ADHD were significantly
      more likely to be involved in higher levels of nicotine use compared with the
      general population. Parental nicotine use was associated with smoking in girls,
      while maternal nicotine use was associated with smoking in boys. Furthermore,
      regular alcohol use in both girls and boys was associated with nicotine use. To
      conclude, early initiation and elevated rates of nicotine and alcohol use are a
      particular risk for adolescents with CD and ADHD.

PMID- 18615351
TI  - Gender aspects on survival among patients admitted to hospital with suspected or
      diagnosed heart failure.
AB  - OBJECTIVES AND DESIGN: There are conflicting data on gender differences in
      survival among heart failure (HF) patients. We prospectively assessed gender
      differences in survival among 930 consecutive patients (464 [49.9%] women, mean
      age 76.1+/-10.1 years), admitted to hospital with suspected or diagnosed HF.
      RESULTS: Overall, women had lower unadjusted mortality hazard ratio (HR) than
      men: HR 0.827; 95% confidence interval (CI) 0.690-0.992; p=0.040. Adjusted HR was
      0.786; 95% CI 0.601-1.028; p=0.079. Unadjusted mortality was significantly higher
      among patients with a discharge HF diagnosis, compared to those without: HR
      1.330; 95% CI 1.107-1.597; p=0.002; adjusted p=0.289. Women and men with a
      discharge HF diagnosis had similar survival: unadjusted HR 1.052; 95% CI 0.829
      1.336; p=0.674; adjusted HR 0.875; 95% CI 0.625-1.225; p=0.437. Women had lower
      mortality risk among patients without a discharge HF diagnosis: HR 0.630, 95% CI
      0.476-0.833, p=0.001; adjusted HR 0.611, p=0.036. CONCLUSION: Prognosis was poor
      among patients hospitalised with suspected or diagnosed HF. Among all patients,
      women had better survival, whereas both sexes had similar survival when the HF
      diagnosis was certified.

PMID- 18615352
TI  - The fallacies of the lipid hypothesis.
AB  - Most researchers to-day consider that a high intake of saturated fat and elevated
      LDL cholesterol are the most important causes of atherosclerosis and coronary
      heart disease. The lipid hypothesis has dominated cardiovascular research and
      prevention for almost half a century although the number of contradictory studies
      may exceed those that are supportive. The harmful influence of a campaign that
      ignores much of the science extends to medical research, health care, food
      production and human life. There is an urgent need to draw attention to the most
      striking contradictions, many of which may be unknown to most doctors and
      researchers.

PMID- 18615353
TI  - YKL-40 a new biomarker in patients with acute coronary syndrome or stable
      coronary artery disease.
AB  - BACKGROUND: YKL-40 is involved in remodelling and angiogenesis in non-cardiac
      inflammatory diseases. Aim was to quantitate plasma YKL-40 in patients with ST
      elevation myocardial infarction (STEMI) or stable chronic coronary artery disease
      (CAD), and YKL-40 gene activation in human myocardium. METHODS AND RESULTS: We
      included 73 patients: I) 20 patients with STEMI; II) 28 patients with stable CAD;
      III) 15 CAD patients referred for coronary by-pass surgery. YKL-40 mRNA
      expression was measured in myocardium subtended by stenotic or occluded arteries
      and areas with no apparent disease; and IV) 10 age-matched healthy controls.
      Plasma YKL-40 was significantly increased in patients with STEMI (88 microg/l,
      median) and CAD (66 microg/l) compared to controls (16 microg/l, p<0.01 for
      both). Plasma YKL-40 correlated with CRP at baseline in STEMI (r=0.53, p=0.02)
      and CAD patients (r=0.41, p=0.031).YKL-40 gene expression was similar in ischemic
      and non-ischemic myocardium. CONCLUSIONS: Plasma YKL-40 was significantly
      increased in patients with STEMI and stable CAD. Further studies will define the
      role of YKL-40 as a clinically useful marker for myocardial ischemia, remodelling
      and maybe prognosis.

PMID- 18615354
TI  - Cholesterol lowering, sudden cardiac death and mortality.
AB  - Sudden cardiac death is the main cause of cardiac mortality. Is blood cholesterol
      a determinant of sudden cardiac death? Does cholesterol lowering result in fewer
      sudden cardiac deaths? Answering these two questions may shed a new light on the
      epidemiology of coronary heart disease and on prevention options. In fact,
      careful analysis of the available data, including randomised trials, indicates
      that, contrary to a widespread opinion, cholesterol lowering does not appear to
      be a very effective way of reducing cardiac and overall mortality in the general
      population.

PMID- 18615355
TI  - Forearm vessel atherosclerosis. A harbinger of carotid disease?
AB  - OBJECTIVES: Atherosclerosis is a systemic disease affecting several vessels of
      the body. Coronary artery patients requiring bypass surgery have increased
      prevalence of carotid artery atherosclerosis which is known to increase operative
      risk in coronary artery bypass surgery (CABG). Radial artery is often screened
      for grafting purposes preoperatively. Our aim was to find out whether
      atherosclerotic changes in forearm vessels are correlated and could reveal risk
      to carotid artery disease. DESIGN: Eighty-five patients planned for elective CABG
      were examined with ultrasonography preoperatively. Biplane ultrasonographic
      scanning was performed on forearm arteries and both carotid arteries. RESULTS:
      Eleven patients had pathologic changes in the wall of forearm vessels. Carotid
      artery disease was found on 19 patients. Forearm vessel pathology was found to
      have correlation to carotid artery disease. When forearm arteries show
      atherosclerotic pathology the risk of having carotid disease is at least five
      fold, in subgroups even higher. CONCLUSIONS: Forearm arterial pathology is
      correlated to carotid artery disease. When forearm vessel pathology is evident in
      preoperative examination, scanning of the carotid vessels should be considered.

PMID- 18615356
TI  - Electrocardiographic ventricular repolarization during cardiovascular autonomic
      function testing in patients with arrhythmogenic right ventricular
      cardiomyopathy.
AB  - OBJECTIVES: Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC)
      experience exercise-related malignant arrhythmias possibly based on delayed
      repolarization in the diseased right ventricle (RV). Autonomic interventions
      might unveil repolarization abnormalities in RV. DESIGN: We recorded 25-lead
      electrocardiograms from nine symptomatic ARVC patients and nine controls during
      rest, Valsalva maneuver, mental stress, handgrip and supine exercise.
      Interventricular repolarization gradient was defined as difference of QT
      intervals between left ventricular (LV) and RV type leads. T-wave peak to T-wave
      end interval (TPE) was defined as the electrocardiographic (ECG) equivalent of
      transmural dispersion of repolarization. RESULTS: ARVC patients showed longer QT
      and TPE intervals in RV than in LV whereas control subjects showed the opposite.
      Valsalva strain reversed the interventricular repolarization gradient from -5+/
      13 to 4+/-20 ms (p<0.02) and induced fluctuation of TPE in ARVC patients.
      CONCLUSIONS: ARVC patients show ECG interventricular repolarization gradient from
      RV to LV and increased ECG transmural dispersion of repolarization in RV.
      Valsalva strain induces fluctuation of interventricular repolarization gradient
      and of transmural dispersion of repolarization in RV possibly modifying the
      substrate for arrhythmias.

PMID- 18615357
TI  - Regression of cirrhosis of the liver detected by elastiometry.

PMID- 18615358
TI  - Pegylated interferon and ribavirin combination therapy for chronic hepatitis C
      virus infection in patients with Child-Pugh Class A liver cirrhosis.
AB  - OBJECTIVE: Pegylated interferon (peg-IFN) and ribavirin (RBV) treatment is less
      effective in patients with hepatitis C virus (HCV) and liver cirrhosis than in
      non-cirrhotic patients. Many patients with advanced liver disease have been
      excluded from the pivotal randomized controlled studies. The aim of this study
      was to investigate the efficacy and tolerability of combination therapy in
      unselected patients with Child-Pugh Class A liver cirrhosis at a Swedish
      university clinic. MATERIAL AND METHODS: The virologic response and adverse
      events were retrospectively analyzed in 104 patients with HCV-associated Child
      Pugh Class A liver cirrhosis who had been treated with peg-IFN and RBV. RESULTS:
      Overall sustained virologic response (SVR) was achieved in 13% genotype 1-, 60%
      genotype 2-, and 31% genotype 3-infected patients. In treatment-naive patients,
      the corresponding rates were 13%, 82%, and 38%, respectively. In 46% of patients,
      treatment was discontinued prematurely owing to lack of virologic response in the
      majority. CONCLUSIONS: SVR rates found in our study, in particular for genotype 1
      patients (13%), were lower than those generally found in randomized controlled
      studies. For cirrhotic patients, new treatment alternatives are urgently needed
      to improve treatment outcome.

PMID- 18615359
TI  - Clinical outcomes and costs among patients with Staphylococcus aureus bacteremia
      and orthopedic device infections.
AB  - We evaluated costs and outcomes of patients with S. aureus bacteremia and
      orthopedic device infections (ODI). Patients with ODI had higher relapse of S.
      aureus infection, compared to bacteremic patients without ODI. Costs and outcomes
      were similar among ODI patients undergoing device removal and those treated with
      debridement and retention.

PMID- 18615360
TI  - High diagnostic yield by CSF-PCR for entero- and herpes simplex viruses and TBEV
      serology in adults with acute aseptic meningitis in Stockholm.
AB  - Acute aseptic meningitis (AAM) affects 10-20/100,000 inhabitants per years in
      Sweden. Up to the beginning of the 1980s the diagnoses were made by virus
      isolation and/or determination of viral antibodies in serum. The development of
      PCR for detection of viruses in CSF samples has increased the sensitivity and
      diagnostic efficiency considerably. We investigated the aetiology of AAM and the
      diagnostic efficiency in an adult population in Stockholm, using a limited first
      line combination of microbiological assays. CSF and serum samples, consecutively
      collected in 419 patients with clinical symptoms of AAM in northern Stockholm
      during 1999-2004, were included. PCR assays for herpes simplex virus (HSV) DNA
      and enterovirus (EV) RNA in the CSF as well as ELISA for IgM in serum to tick
      borne encephalitis virus (TBEV) were performed routinely. A viral diagnosis was
      obtained in 255 of the 419 cases (62%) with these routinely performed assays.
      Clinical findings in combination with additional diagnostic tests resulted in an
      overall aetiological yield of 72%. EV was the major causative agent (27%)
      followed by TBEV (21%) and HSV-2 (19%). We conclude that consistent use of CSF
      PCR for EV and HSV and TBEV serology established a diagnosis in the majority of
      AAM patients.

PMID- 18615362
TI  - Taking a doctorate in family medicine in the Nordic countries.

PMID- 18615361
TI  - Bacterial superinfection in upper respiratory tract infections estimated by
      increases in CRP values: a diagnostic follow-up in primary care.
AB  - OBJECTIVE: The aim of this study was to estimate the rate of bacterial
      superinfection in patients with URTI by using on-site determination of C-reactive
      protein (CRP). DESIGN: A prospective cohort study. SETTING: A total of 30 primary
      care practices. SUBJECTS: Patients with URTI. INTERVENTION: The CRP value was
      determined at the first consultation and at a follow-up within 3-5 days. CRP
      values of 30 units (mg) or higher were considered to be an indication of
      bacterial involvement. MAIN OUTCOME MEASURES: CRP values during follow-up and
      duration of illness. RESULTS: Among the 506 patients included, 73.1% exhibited a
      CRP value below the defined limit at their first visit and were considered to
      suffer from URTI of viral origin. The rate of subsequent bacterial superinfection
      was 8.1%. Compared with patients suffering from URTI of bacterial or viral origin
      the duration of illness in patients with bacterial superinfection was
      significantly longer. CONCLUSION: During follow-up of patients with URTI, the
      prevalence of bacterial superinfection detected by using a near patient CRP
      determination is surprisingly low. This result should help to reduce the
      prescription rate of antibiotics in primary care.

PMID- 18615363
TI  - An update on the medical therapy of advanced metastatic renal cell carcinoma.
AB  - The effectiveness of multikinase inhibitors in first- and second-line therapy of
      metastatic renal cell carcinoma (RCC) has been evaluated in various clinical
      studies. Initial results indicate an increased response rate and a prolonged
      progression-free survival compared with cytokine-containing therapeutic
      approaches. The new multitargeted kinase inhibitors sorafenib (Nexavar/BAY 43
      9006) and sunitinib (Sutent/SUO 11248) interfere mainly with vascular endothelial
      growth factor and platelet-derived growth factor pathways. Recently,
      temsirolimus, a specific inhibitor of mammalian target of rapamycin, demonstrated
      activity in RCC patients with poor prognosis. This review discusses the
      effectiveness of the most frequently used substances for systemically progressive
      RCC in consideration of the currently available clinical data.

PMID- 18615364
TI  - Chronic abacterial prostatitis: Living with a troublesome disease affecting many
      aspects of life.
AB  - OBJECTIVE: Chronic abacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS)
      is a disease of yet not clarified aetiology where the symptoms, voiding
      dysfunction and pelvic pain are difficult to alleviate. The aim of this study is
      to arrive at an understanding of how it influences the individual afflicted.
      MATERIALS AND METHODS: Ten men with CP/CPPS were interviewed about their
      situation. The interviews were transcribed and analysed using a phenomenological
      perspective. RESULTS: The often severe symptoms influence well-being and a life
      in more or less constant fear of a relapse is described. A majority manages,
      despite the problems, to endure and conceal the problems. The situation can,
      however, become unbearable and force the man to seek solitude or lose his temper.
      Social isolation and restrictions at work and during recreational activities were
      thus reported by those more severely afflicted. Confirmation from the healthcare
      system that the disease is not life threatening and affirmation that they are not
      unwanted and neglected are essential. CONCLUSIONS: Men with CP/CPPS are mostly
      able to live a normal life, although it is often difficult and the people around
      them are rarely given an insight into their world, where their existence is
      focused on attempts to obtain confirmation, control abrupt mood fluctuations and
      develop coping strategies. They have much in common with other patient groups
      afflicted by chronic pain, such as difficulties in performing at work and severe
      fatigue. More specific for CP/CPPS is the presence of additional symptoms, which
      individually can severely impair quality of life. Accepting the situation and
      developing coping strategies are consequently challenges for a man with CP/CPPS.

PMID- 18615365
TI  - Urinary incontinence: Evaluation of an information campaign directed towards the
      general public.
AB  - OBJECTIVE: To study and evaluate the effect of an information campaign in the
      form of a brochure on urinary incontinence (UI) directed towards the general
      public, concerning knowledge, individual health behaviour, self-reported
      healthcare utilization and how the information was perceived. MATERIAL AND
      METHODS: Within a community in central Sweden a random sample of the population,
      in age groups from 18 years upwards, was selected from the population registry,
      resulting in a total sample of 3,658 people. The study group was sent the
      brochure "Treatment of urinary incontinence", produced by SBU (Swedish Council on
      Technology Assessment in Health Care) in March 2003 and a questionnaire 1-2
      months after the brochure was received. RESULTS: The overall response rate was
      47.5%. Eighty per cent of the responders stated UI as an important health problem
      in society and 66% that they had gained new knowledge on UI. Twenty-eight per
      cent of the responders reported a current or previous history of UI, of whom 49%
      felt that they had received useful information for self-treatment and 21% had
      begun self-treatment. CONCLUSION: This population-based study found that the
      distribution of a brochure on UI to the general public was well received and can
      be an efficient method to spread knowledge and encourage self-management.

PMID- 18615367
TI  - Revised Korean medication algorithm for bipolar disorder.
AB  - The rapid progress in treatments for bipolar disorder makes it necessary to
      revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP)
      published in 2002. This study was performed to timely revise KMAP-BP 2002. A
      questionnaire comprising 37 questions and 645 treatment options was developed for
      surveying the opinions of Korean experts. We classified the opinions into three
      categories: first-, second-, and third-line treatments. Fifty-three (75.7%) of
      the 70 selected experts answered the questionnaire. For an acute manic episode,
      the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) was
      the preferred first-line treatment. Most experts recommended divalproex and
      lithium as MSs, and olanzapine, quetiapine, and risperidone as AAPs. For
      moderately to severely depressed bipolar patients, MS monotherapy and a
      combination of an MS and an antidepressant (AD) were considered to be preferred
      treatments respectively. A combination of an MS and an AD was the preferred
      strategy in severe nonpsychotic depression. Most ADs were rated as second-line
      drugs. Overall, the preference for lamotrigine and AAPs was higher than in KMAP
      BP 2002. The algorithm was developed mainly using consensus among experts
      supplemented with findings of recent clinical trials to ensure that our algorithm
      was both up to date and balanced. These results suggest that the medication
      strategies of KMAP-BP are changing rapidly, reflecting recent studies and
      clinical experiences.

PMID- 18615368
TI  - Quetiapine-associated dysphagia.
AB  - We report a case of quetiapine-induced dysphagia in a geriatric patient which
      improved with discontinuation of the antipsychotic. The patient had developed
      dysphagia while being treated with antipsychotics for bipolar disorder. The
      patient's dysphagia showed significant improvement when she was taken off
      quetiapine. We review the available literature on antipsychotic-related dysphagia
      and suggest that clinicians need to be aware of the potential for this syndrome
      even with lower potency antipsychotics.

PMID- 18615369
TI  - Off-pump coronary artery bypass surgery may reduce the incidence of stroke in
      patients with significant left main stem disease.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery in patients with left
      main stem (LMS) disease remains controversial. This meta-analysis compares early
      outcomes of OPCAB surgery with on-pump coronary artery bypass (ONCAB) surgery in
      patients with significant LMS disease, focusing on the outcomes stroke and
      transient ischemic attack (TIA). METHODS: This is a meta-analysis of non
      randomized comparative peer-reviewed publications sourced from a systematic
      search of Embase, Medline, Cochrane, Google Scholar and CINAHL (1965-2007). A
      random effects model was used and heterogeneity was assessed. RESULTS: Nine
      studies (4411 patients) dating from 2000-2007, of whom 1036 (23.5 %) underwent
      OPCAB and 3375 (76.5 %) ONCAB, were included. The incidence of stroke was lower
      in the OPCAB group (OR 0.17 [95 % CI 0.05 to 0.60]). Early mortality, length of
      hospital stay, blood loss and inotropic requirements were significantly favored
      by OPCAB surgery. CONCLUSIONS: OPCAB may offer a neurological benefit in patients
      with significant LMS disease undergoing coronary artery bypass grafting.

PMID- 18615370
TI  - Epicardial versus transvenous left ventricular lead placement in patients
      receiving cardiac resynchronization therapy: results from a randomized
      prospective study.
AB  - BACKGROUND: The aim of this prospective study was to determine the differences in
      left ventricular (LV) lead positioning for cardiac resynchronization therapy
      (CRT): comparing a percutaneous transvenous approach via the coronary sinus
      versus epimyocardial placement via a left lateral mini-thoracotomy. METHODS:
      Eighty consecutive patients with symptomatic left ventricular dysfunction and an
      indication for CRT were randomized to receive either a transvenous (n = 40) or
      epicardial (n = 40) LV-lead placement. Postoperative follow-up included
      assessment of NYHA functional class, ECG and echocardiography. RESULTS: The
      transvenous group had a shorter ICU stay (0.66 vs. 3.8 days) and shorter
      ventilation times (0.34 vs. 3.2 h). The epicardial group had less exposure to
      radiation (7.4 vs. 23 min) and required less use of contrast medium (3.24 vs. 61
      ml). At 6 months follow-up, no major differences in LV-lead parameters
      (threshold, sensing, and impedance) were observed. CONCLUSION: Both epicardial
      and transvenous LV-lead placement for CRT therapy are safe and effective. The
      transvenous approach is less invasive and should be considered the standard
      procedure for patients without renal insufficiency. However, in a case of
      difficult coronary venous anatomy with the inability to position the lead as
      desired, epicardial LV-lead placement remains an alternative option.

PMID- 18615371
TI  - Early and late results of restrictive mitral valve annuloplasty in 121 patients
      with cardiomyopathy and chronic mitral regurgitation.
AB  - OBJECTIVE: This study investigated the early and late results of restrictive
      mitral valve (MV) annuloplasty in patients with chronic mitral regurgitation (MR)
      and advanced ischemic (ICM) or dilated cardiomyopathy (DCM). METHODS: From
      October 2001 to September 2006, 121 patients (age: 69 +/- 9 years) with a left
      ventricular ejection fraction (LVEF) of 30 +/- 9 % and chronic MR grade 3 - 4
      (ICM: n = 102, DCM: n = 19) underwent restrictive prosthetic ring annuloplasty
      (downsizing of 2.7 +/- 0.8 ring sizes). Eighty-five ICM-patients had indications
      for concomitant coronary artery bypass grafting (CABG). All patients were
      restudied at 7 +/- 1 days, 3 +/- 1 and 30 +/- 12 months after surgery to assess
      survival, residual MR, New York Heart Association (NYHA) class and left
      ventricular (LV) function (end-systolic/end-diastolic dimensions/volume indexes
      and LVEF). Data were analyzed exploratively. RESULTS: 30-day mortality was 3.3 %;
      survival at follow-up was 95 % and 91 %, respectively. Postoperative recurrence
      of significant MR (> grade 2) was absent in all patients. NYHA class, LV
      dimensions/volume indexes and LVEF improved significantly after surgery in both
      groups ( P < 0.0005). A prediction of continuous postoperative improvement of
      myocardial function in the sense of reverse remodeling could be demonstrated by
      univariate logistic regression for ischemic etiology and concomitant CABG ( P =
      0.0001). In DCM-patients or ICM-patients without CABG, the postoperative benefit
      on myocardial function was limited. CONCLUSION: Restrictive mitral valve (MV)
      annuloplasty corrected chronic MR in cardiomyopathy patients with low mortality
      and improved contractility. Surgery also prevented recurrence of significant MR,
      although the phenomenon of postoperative continuous reverse myocardial remodeling
      could not be verified in cases with a non-ischemic etiology or ICM without
      concomitant CABG.

PMID- 18615372
TI  - Therapeutic optimization of atrioventricular delay in cardiosurgical ICU patients
      by noninvasive cardiac output measurements versus pulse contour analysis.
AB  - BACKGROUND: Optimizing atrioventricular (AV) delay improves cardiac output and
      postoperative outcome. Impedance cardiography (ICG) is a non-invasive method for
      CO measurement. This study evaluates the ability of two ICG methods to determine
      the optimal AV delay (OAVD) and to compare ICG with invasive PICCO measurements.
      METHODS: In 14 cardiosurgical ICU patients (age 70.4 +/- 12.0 yrs) with temporary
      pacing wires, OAVD was determined by pulse contour analysis (PICCO) and ICG
      (conventional ICG [CI] and electrical velocimetry [EV] ICG monitors). Cardiac
      output (CO) and stroke volume (SV) were measured during DDD pacing with AVD
      varying from 70 to 270 ms in 20-ms increments. RESULTS: Measured OAV showed a
      linear correlation between PICCO and ICG: CI (r = 0.82, P < 0.0002) and EV (r =
      0.84, P < 0.0002). The mean OAVD deviation between PICCO and ICG was 15.7 +/-
      21.0 ms (CI) and 17.1 +/- 20.5 ms (EV). Hemodynamic parameters (SV increase OAVD
      against worst case) improved significantly (+ 11.7 +/- 7.2 %, P < 0.0001).
      CONCLUSION: Inappropriate selection of AVD can compromise the hemodynamic
      situation of cardiosurgical patients. As it is totally noninvasive, ICG is a
      reliable and effective tool for tailoring AVD. Both systems (CI and EV) offer
      valid OAV determination.

PMID- 18615373
TI  - Proton pump inhibitors may increase the risk of delayed bleeding complications
      after open heart surgery if used concomitantly with warfarin.
AB  - OBJECTIVES: The American Food and Drug Administration has suggested that proton
      pump inhibitors increase the international normalized ratio (INR) when used
      concomitantly with warfarin, by being metabolized by cytochrome P450 2C19. We
      therefore reviewed patients taking warfarin. METHODS AND RESULTS: Two hundred and
      forty patients who took warfarin after surgery were divided into two groups:
      Group I (n = 114) had rabeprazole (10 mg/day) and Group II (n = 126) had
      lansoprazole (15 mg/day). The initial dose of warfarin was 3 mg and INR was
      initially assessed on postoperative day 4. Initial INR was significantly lower in
      Group I (1.66 +/- 0.87) than in Group II (2.06 +/- 1.03, P = 0.0011). Delayed
      cardiac tamponade and hemothorax occurred as complications in 6 and 1 patients,
      respectively, in Group II from 5 days to 3 months postoperatively. At the time of
      the occurrence of complications, the average INR increased to 3.95 (range from
      3.11 to 5.86). There were no patients with delayed bleeding in Group I ( P =
      0.015). CONCLUSIONS: These results suggest that lansoprazole emphasizes the
      effects of warfarin. Rabeprazole could be safely used concomitantly with
      warfarin.

PMID- 18615374
TI  - Videothoracoscopic excision of mediastinal tumors and cysts using the harmonic
      scalpel.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and reliability of
      the harmonic scalpel for performing VATS excisions of mediastinal tumors and
      cysts. METHODS: We have prospectively studied 19 cases presenting with a
      mediastinal tumor or cyst operated on consecutively since January 2003. RESULTS:
      We performed 10 left-sided and 9 right-sided VATS procedures; the mean age at
      operation was 50 +/- 15 years. Two masses were in the anterior mediastinum, 5 in
      the middle mediastinum and 12 in the posterior mediastinum. One patient required
      conversion to a minithoracotomy for bleeding. The maximum tumor diameter was 38
      +/- 14 mm and the maximum cyst dimension was 55 +/- 20 mm. The mean operating
      time was 66 +/- 28 min. Three patients experienced minor complications. The
      postoperative hospital stay was 3.5 +/- 1.7 days, and we had no mortality.
      Histopathology revealed 1 esophageal leiomyosarcoma, 1 Langerhans cell
      histiocytosis X, 1 hamartoma, 5 schwannomas, 1 neurofibroma, 1 malignant
      peripheral nerve sheath tumor, 1 reactive lymphadenopathy, 1 tuberculous
      lymphadenopathy, 1 cystic hygroma, 2 bronchogenic cysts, 2 foregut cysts, 1
      thymic cyst, and 1 pleuropericardial cyst. There has been no recurrence of tumor
      or cyst on follow-up. CONCLUSIONS: Videothoracoscopic excision of mediastinal
      tumors and cysts can be safely performed using the harmonic scalpel with a low
      morbidity and mortality.

PMID- 18615375
TI  - Clinical experience of Nuss procedure for pectus excavatum in adult female
      patients.
AB  - BACKGROUND: Pectus excavatum (PE) repair by Nuss procedure is well established in
      pediatrics, but studies of adult female patients are rare. We analyzed the
      efficacy of the Nuss procedure in adult, female PE patients. METHODS: We
      retrospectively reviewed adult patients who underwent Nuss repair of PE from
      April 2005 to November 2007. Precise morphologic characterization of the pectus
      allowed an appropriate shaping of the bars to achieve a symmetric repair.
      RESULTS: Out of 126 consecutive adult patients who underwent the Nuss procedure
      at our institution, 15 women with a mean age of 24.6 +/- 4.01 years were enrolled
      in the study. Their preoperative Haller index had a mean of 5.72 +/- 2.38. Seven
      patients (46.67 %) underwent repair with the insertion of double pectus bars.
      Complications included transient bilateral pneumothorax (n = 1) and right-sided
      pleural effusion (n = 1). One patient received a subsequent breast augmentation,
      which yielded a better thoracic contour. CONCLUSIONS: The Nuss procedure offers a
      high satisfaction rate and an acceptable complication rate for PE repair in adult
      female patients. A subsequent surgery for breast augmentation can be considered
      after the Nuss repair has stabilized.

PMID- 18615376
TI  - Solitary fibrous tumor of the pleura.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical behavior of
      solitary fibrous tumors of the pleura and consider the optimal surgical approach
      for these rare tumors. MATERIAL AND METHODS: We retrospectively reviewed the
      records of nine patients who underwent thoracotomy for tumor resection in our
      clinic between 1997 and 2006. RESULTS: Nine patients were operated in this period
      and their median age was 46 years. None of them had been exposed to asbestos.
      Symptoms were present in 8 patients. All patients underwent thoracotomy. The
      tumor originated from the visceral pleura in 7 patients and was parietal in 2.
      All tumors were totally excised. The median diameter of the tumors was 9 cm
      (range 4-24 cm). Pathological investigation reported the tumors to be a benign
      solitary fibrous tumor of the pleura in all 9 patients. Resection was complete in
      all patients. There was no postoperative mortality and no major complications. No
      recurrence was observed during a median follow-up of 74 months. CONCLUSIONS:
      Solitary fibrous tumors of the pleura are rare neoplasms and can have giant
      diameters. Complete surgical resection is the optimal treatment. The risk of
      malignant transformation of such large masses should be borne in mind.

PMID- 18615377
TI  - Solitary fibrous tumors of the pleura: clinicopathological characteristics,
      immunohistochemical profiles, and surgical outcomes with long-term follow-up.
AB  - BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) are rare. The aims of
      this study were (1) to characterize their clinicopathological features more
      precisely; (2) to determine whether an immunohistochemical (IHC) study can be
      helpful in distinguishing benign from malignant SFTPs; and (3) to provide more
      complete information to better predict prognosis. METHODS: Microscopic
      examinations of tumorous specimens from 15 patients were repeated and the tumors
      were reclassified. In addition to evaluating clinicopathological variables,
      expressions of p16, p53, Ki-67, CD-117, estrogen receptor (ER), and progesterone
      receptor (PR) biomarkers were studied and their clinicopathological and
      prognostic significance analyzed. RESULTS: Of the 15 enrolled patients (mean age
      57 years; 8 men and 7 women), 8 were symptomatic when diagnosed. Eight patients
      underwent CT-guided needle biopsies before surgery and two had positive findings.
      All cytologic studies of pleural effusion were negative for malignant cells.
      Complete pleural resection with adequate safe margins was performed for all
      patients. Eleven cases proved to have benign tumors and 4 had malignancies. Local
      recurrence occurred in 3 cases and distant metastasis in one. Conventional
      factors, including tumor size, tumor shape, symptomatic presentation, and
      histological type did not affect prognosis. Interestingly, p16 expression was
      significantly associated with tumor recurrence ( P = 0.009). CONCLUSION: Complete
      pleural resection with adequate safe margins can achieve satisfactory outcomes in
      a majority of cases, but long-term follow-up for all patients is recommended due
      to the potential for late tumor recurrence. Conventional clinicopathological
      variables do not affect prognosis. However, IHC studies of the CD-34 and bcl-2
      biomarkers can be important for further differential diagnosis, and p16
      expression can be used to predict tumor recurrence.

PMID- 18615378
TI  - ICU controlled delay for acute type a aortic dissection repair after intervention
      for total visceral malperfusion: a way out of a dilemma?
AB  - Despite immediate surgical repair of the entry site in acute thoracic aortic
      dissection with visceral malperfusion, the results are poor. Primary restitution
      of visceral flow by intervention might be one way to cope with this problem, but
      probably causes ischemia/reperfusion associated problems after prolonged complete
      visceral ischemia. In this report, we demonstrate a successful attempt of
      controlled delay of thoracic aortic surgical repair after visceral flow
      restitution with stable hemodynamics.

PMID- 18615379
TI  - Mini-sternotomy approach for aortic valve replacement in the patient with
      retrosternal gastric tube.
AB  - This case report details our experience of aortic valve replacement(AVR)
      following esophagectomy for esophageal cancer.The route of the retrosternal
      gastric tube was clearly visualized by esophagogram and CT. A mini-sternotomy was
      performed safely, resulting in minimal dissection of the retrosternal adhesion
      and a good exposure to institute extracorporeal circulation and perform the AVR.
      The patient was discharged uneventfully and was in NYHA class I at three months
      after surgery. A ministernotomy is a safe alternative approach for good exposure
      of the heart when performing AVR in patients with a retrosternal gastric tube.

PMID- 18615380
TI  - Pseudoaneurysm of brachiocephalic artery caused by blunt chest trauma.
AB  - Traumatic aneurysms of the brachiocephalic artery may cause mostly nonspecific
      symptoms, which may lead to a misdiagnosis with serious complications. This
      report describes a 27-year-old woman with a traumatic aneurysm of the
      brachiocephalic artery,suffering from lung symptoms. Brachiocephalic aneurysm and
      bronchiectasis were diagnosed by chest CT scan. A bypass from the ascending aorta
      to the distal brachiocephalic artery with a prosthetic graft and aneurysmectomy
      were performed without the use of cardiopulmonary bypass. The patient had an
      uneventful recovery.

PMID- 18615381
TI  - Giant mass due to Castleman's disease causing superior vena cava syndrome.
AB  - Castleman's disease is an uncommon disorder occurring mostly in patients
      presenting with localized mediastinal lymphadenopathy.It is usually asymptomatic.
      With localized disease, surgical excision is curative. Castleman's disease can
      very rarely present as superior vena cava syndrome. We describe a case of
      mediastinal Castleman's disease which presented as vena cava superior syndrome;
      it is the largest mediastinal mass from Castleman's disease reported in the
      literature.

PMID- 18615382
TI  - Primary chylopericardium with pulmonary lymphedema.
AB  - Primary chylopericardium is an uncommon entity, and its association with
      pulmonary lymphedema has been rarely reported.We describe a case of primary
      chylopericardium with pulmonary lymphedema developing into hypoxemia. The
      pulmonary lesions were histologically diagnosed as pulmonary lymphangiectasis and
      lymphedema on lung biopsies. Lymphedema seems to suggest the existence of chylous
      reflux with pulmonary lymphangiectasis. The patient underwent pericardial
      fenestration and resection of the thoracic duct. After the operation, the chylous
      accumulation in the pericardial cavity had disappeared,and hypoxemia improved
      following the disappearance of the pulmonary lesions.

PMID- 18615383
TI  - Askin's tumor: a rare chest wall neoplasm. Case report and short review.
AB  - Askin's tumor is a rare neoplasm of the chest wall with a dismalprognosis. We
      report the case of 16-year-old girl presenting with a painful mass on the right
      anterolateral chest wall. The patient underwent radical mass resection.
      Histopathology revealed an Askin's tumor infiltrating the 5th ipsilateral rib and
      pleura. The girl subsequently received postoperative chemo-radio therapy with a
      satisfactory response. This is the first reported case of Askin's tumor in Greece
      and we focus on the clinical, radiological,pathological and therapeutic aspects
      of this rare entity.

PMID- 18615384
TI  - Awake endoscopic thymectomy via an infrasternal approach using sternal lifting.
AB  - Recently, thoracic epidural anesthesia (TEA) has been employed to perform awake
      thoracic surgery procedures. This is the first report that describes an awake
      endoscopic thymectomy through an infrasternal approach using sternal lifting.
      This procedure allows the patient to eat, drink, and walk on the day of surgery.
      TEA can also be used for postoperative analgesia. Our experiences have shown that
      it is safe and beneficial to apply this procedure.

PMID- 18615385
TI  - Another disastrous outcome following aortic root replacement with the Shelhigh No
      react aortic valved tube.

PMID- 18615386
TI  - Interrupted vs. uninterrupted training on BMD during growth.
AB  - This study compared a resistance training program where the exercise was
      uninterrupted (UT, i.e., continuous repetitions) against a resistance training
      program where the exercise was interrupted (IT, i.e., 3 exercise sessions during
      a training day) for enhancing bone modeling and bone mineral density (BMD) in
      maturating animals. The total volume of work performed between the two resistance
      training programs was equivalent by design. 24 young male rats were randomly
      divided into Control (Con, n = 8), UT (n = 8) and IT (n = 8) resistance trained
      groups. The UT and IT groups were conditioned to climb a vertical ladder with
      weights appended to their tail 3 days/wk for 6 wks. After the 6-wk program, serum
      osteocalcin was not significantly different between groups, whereas the adjusted
      urinary deoxypyridinoline (DPD) was significantly lower for both UT (81.03 +/-
      5.53) and IT (88.30 +/- 7.29) compared to Con (128.13 +/- 9.99). Tibial BMD
      (assessed via DXA) was significantly greater for UT (0.222 +/- 0.005 g/cm (2))
      and IT (0.219 +/- 0.003 g/cm (2)) when compared to Con (0.205 +/- 0.004 g/cm
      (2)). There was no significant difference in DPD or BMD between UT and IT groups.
      The results indicate that both interrupted and continuous, uninterrupted
      resistance training programs were equally effective in stimulating bone modeling.

PMID- 18615387
TI  - Upright MRI of the shoulder demonstrates labrum dynamics.
AB  - Conservative treatment of anterior shoulder luxation includes immobilization in
      internal rotation. This has been increasingly debated, but imaging techniques in
      supine position do not reflect the influence of gravity. To examine glenoid
      labrum dynamics, the shoulders of 15 healthy subjects were imaged in standing
      position at different (0, 15, 30) degrees of external rotation using the Upright
      MRI. The functional length of the anterior labrum was measured. Due to an
      increasing tension of the anterior capsule, functional labrum length increased
      the more, the more the humerus was externally rotated. The results underline the
      usefulness of the Upright MRI and support the concept of immobilization in the
      position of external rotation.

PMID- 18615389
TI  - Prevention and treatment of thrombosis in microvascular surgery.
AB  - Microvascular free tissue transfer is associated with a 1 to 5% failure rate,
      most commonly as a result of thrombosis in the region of the vascular anastomosis
      or the distal flap microcirculation. Although many laboratory and clinical
      studies have been performed, there is no consensus on the efficacy and optimal
      dosage of various pharmacological agents available for the prevention and
      treatment of thrombosis in microvascular surgery. Some agents have potentially
      serious side effects; and all agents carry the risks of undesirable bleeding and
      hematoma formation. We review the current experimental and clinical evidence
      regarding the agents commonly used to prevent and treat thrombosis in
      microvascular surgery and make practical recommendations for the management of
      vascular compromise in free flaps.

PMID- 18615388
TI  - Pre-exercise carbohydrate status influences carbohydrate-mediated attenuation of
      post-exercise cytokine responses.
AB  - Most studies investigating the effects of acute carbohydrate (CHO) ingestion on
      post-exercise cytokine responses have involved fasted athletes. This study
      characterised the effects of acute CHO beverage ingestion preceded by consumption
      of a CHO-containing pre-exercise meal. Sixteen highly-trained male
      cyclists/triathletes (age: 30.6 +/- 5.6 y; V O (2max): 64.8 +/- 4.7 ml . kg . min
      (-1) [mean +/- SD]) undertook two cycle ergometry trials involving randomised
      consumption of a 10 % CHO beverage (15 mL . kg (-1) . hr (-1)) or water (H (2)O).
      Trials were undertaken 2 h after a breakfast providing 2.1 g CHO . kg (-1) body
      mass (BM) (48 kJ . kg (-1) BM) and consisted of 100 min steady state cycle
      ergometry at 70 % V O (2max) followed by a time trial of approximately 30 min
      duration. Blood samples were collected pre-, post- and 1 h post-exercise for
      measurement of Interleukin (IL)-6, IL-8, IL-10 and IL-1ra. Time-trial performance
      was not substantially different between CHO and H (2)O trials (4.5 %, p = 0.42).
      Neither IL-6 nor IL-8 responses were substantially reduced in the CHO compared to
      the H (2)O trial. There was a substantial reduction in IL-10 (32 %, p = 0.05) and
      IL-1ra (43 %, p = 0.02) responses at 1 h post-exercise with CHO compared to H
      (2)O ingestion. In conclusion, the previously shown attenuating effects of CHO
      ingestion during exercise on cytokine responses appear reduced when athletes
      consume a CHO-containing pre-exercise meal.

PMID- 18615390
TI  - [Technology in the operating room of the future--integration of imaging into
      image guided surgery].

PMID- 18615391
TI  - [Intraoperative neuromonitoring of the recurrent laryngeal nerve--informing the
      patient about the possibility of neuromonitoring in difficult thyroid
      operations].

PMID- 18615392
TI  - Somatostatin receptors in GH-secreting pituitary adenomas--their relationship to
      the response to octreotide.
AB  - Twenty pituitary adenomas, surgically removed from patients suffering from
      acromegaly, were studied. The tumours were immunostained with anti-GH and anti
      PRL antibodies and with antibodies raised against particular subtypes of
      somatostatin receptors (rsst1-5). Expression of rsst immunoreactivity was scored
      using the following scale: 0--negative reaction, 1--weak reaction, 2--moderate
      reaction, 3--strong reaction. In 15 patients in whom the GH response to the acute
      administration of 200 ug octreotide was tested the correlation between the
      expression of rsst and the percentage of GH drop was estimated. All the tumours
      were GH-immunopositive and in the majority (14/20) co-expression of PRL was also
      found. All the adenomas examined expressed rsst2A (20/20) and rsst5 (12/12)
      receptor proteins. Receptors sst2B and rsst3 were found in all but one of the
      tumours examined (19/20 and 11/12, respectively). None of tumours investigated
      presented rsst4 immunopositivity. The mixed (GH/PRL) adenomas showed a tendency
      to a higher expression of rsst2A + + rsst2B and a greater response to octreotide
      administration. A significant positive correlation was found between rsst2A +
      rsst2B expressions and a drop in GH after octreotide. To conclude, the GH
      inhibiting effect of octreotide depends on the intensity of expression of both
      rsst2A and rsst2B. Both isoforms of rsst2 mediate the same biological response
      (inhibition of GH secretion) in GH-secreting and GH/PRL-secreting adenomas.

PMID- 18615393
TI  - The effects of melatonin on glutathione peroxidase activity in serum and
      erythrocytes after adriamycin in normal and pinealectomised rats.
AB  - INTRODUCTION: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in
      the treatment of leukaemias, lymphomas and many solid tumours. However, its
      clinical usage is often limited by cardiotoxicity, induced by oxygen radical
      damage of the membrane lipids. Melatonin (MEL) is a well-known antioxidant. It
      has been shown that MEL can scavenge free radicals, both directly and indirectly,
      stimulating the activity of antioxidative enzymes such as glutathione peroxidase
      (GSH-Px). THE AIM OF THE STUDY: The aim of the study was to examine the effect of
      MEL on serum and erythrocyte GSH-Px activity after ADR in normal and
      pinealectomised rats. MATERIAL AND METHODS: Wistar rats were divided into the
      three groups: control animals (Intact), sham-operated (Sham-PX) and
      pinealectomised (Px). Each of the groups was divided into four subgroups,
      injected with: 1--saline, 2--MEL, 3--ADR and 4--ADR + MEL. ADR was administered 2
      months after Px as a single dose (15 mg/kg, i.p.) 1 hour after the fourth
      melatonin injection. Melatonin (5 mg/kg, i.p.) was administered for 4 days before
      and 2 days after ADR. After 6 days of treatment, the rats were killed by
      decapitation. Their blood was collected for measurements. RESULTS: In serum GSH
      Px activity decreased in all the groups after ADR. Pinealectomy decreased the
      activity of the enzyme in all the groups of animals examined. In erythrocytes GSH
      Px decreased after ADR in the Px-animals. The effect of pinealectomy on
      erythrocyte GSH-Px activity was not as strongly expressed as serum GSH-Px
      activity. MEL did not change GSH-Px activity after ADR. CONCLUSION: Melatonin, in
      pharmacological concentrations, did not influence the activity of GSH-Px, either
      in normal or in pinealectomised rats after ADR. A deficiency of endogenous
      melatonin production may inhibit GSH-Px activity.

PMID- 18615394
TI  - Ghrelin as a potential blood pressure reducing factor in obese women during
      weight loss treatment.
AB  - BACKGROUND: In animal models ghrelin reduces cardiac afterload and increases
      cardiac output via receptors in the cardiovascular system. The aim of our study
      was to evaluate a potential relationship between weight loss treatment, blood
      pressure and serum ghrelin concentrations in obese women. MATERIAL AND METHODS: A
      group of 37 obese premenopausal women with no previous history of hypertension
      (BMI: 36.5 +/- 5 kg/m2) were involved in the study. Blood pressure and serum
      ghrelin levels were assessed before and after a three-month weight reduction
      treatment, which consisted of a diet of 1000 kcal/day and physical exercise. Body
      composition was determined by impedance analysis using Bodystat. RESULTS:
      Following weight loss (mean 8.9 +/- 4.8 kg) SBP decreased (120 +/- 13 vs. 115 +/-
      14 mm Hg, p = 0.01) and serum ghrelin levels increased significantly (66.9 +/-
      13.7 vs. 73.9 +/- 15.4 pg/ml; p = 0.005). There were significant correlations
      between values for ghrelin levels after weight loss and SBP (r = -0.45, p =
      0.02), DBP (r = -0.41, p < 0.05), and between Deltaghrelin levels and DeltaSBP (r
      = 0.52, p = 0.006), DeltaDBP (r = 0.53, p = 0.005). There was a positive
      correlation between an increase in ghrelin and a decrease in percentage body fat
      during weight loss (r = 0.51; p = 0.002). CONCLUSION: The results seem to provide
      evidence that weight loss may decrease blood pressure in obese patients via a
      ghrelin-dependent mechanism.

PMID- 18615395
TI  - The polymorphism in insulin receptor substrate-1 gene and birth weight in
      neonates at term.
AB  - BACKGROUND: The mutation of the IRS-1 gene is one of the genetic risk factors
      which, it is speculated, is associated with insulin resistance or predisposition
      to type 2 diabetes. The aim of our study was to evaluate the association between
      the Gly972Arg polymorphism in the IRS-1 gene and birth weight in newborn children
      with adequate gestational age. MATERIAL AND METHODS: 100 newborn children with
      adequate gestational age (38-42 weeks), whose mother had no disorders during
      pregnancy, were studied. Genomic DNA was extracted from umbilical cord blood
      leukocytes, and Gly972Arg polymorphism in the IRS-1 gene was genotyped using the
      PCR-based method. RESULTS: Birth weight was significantly lower in the newborn
      with the IRS-1 Gly972Arg polymorphism compared with a control group (3161.75 +/-
      380.86 g vs. 3427.92 +/- 468.86 g). Body length and head circumference at birth
      were also lower in the neonates with that polymorphism (54.38 +/- 3.13 cm vs.
      52.69 +/- 2.91 cm, and 34.08 +/- 1.47 vs. 33.63 +/- 0.81, respectively).
      CONCLUSIONS: The results suggest that the Gly972Arg genotype is associated with
      lower birth weight, body length and head circumference in neonates with adequate
      gestational age.

PMID- 18615396
TI  - [Obesity and bone metabolism].
AB  - Both bone and adipose tissue change their size, shape and distribution during the
      whole human being's life. Many factors, including genetic factors, hormones and
      activity of nervous system are responsible for these changes. It is generally
      accepted that obesity has a protective effect on bone tissue. On the other hand
      some authors present an opposite results--the lack of beneficial effect of
      obesity on development of osteoporosis fractures. The aim of this article was to
      present and discuss the relations between adipose tissue and bone metabolism.

PMID- 18615397
TI  - [Does type 2 diabetes predispose to osteoporotic bone fractures?].
AB  - Chronic complications of diabetes are associated mainly with changes in major and
      small arterial vessels as well as in peripheral and autonomic fibers of the
      nervous system. For years it has been suggested that DM2 does not predispose to
      osteoporosis because bone mineral density (BMD) in DM2 patients is commonly
      normal or even increased. However, results of recent large cross-sectional
      studies have indicated that patients with DM2 have significantly increased risk
      of bone fractures, predominantly hip fractures (by 70%). Results of these studies
      suggest that the increased risk of fractures in DM2 is independent of BMD. In
      this group of patients is frequently associated the loss of vision caused by
      diabetic eye disease, peripheral neuropathy, arterial hypertension, orthostatic
      hypotonia (caused by autonomic neuropathy or/and by concomitant antihypertensive
      treatment), and ischemic disease of the brain, heart and lower extremities-
      conditions that predispose to falls. There are no specific methods of prophylaxis
      and treatment of osteoporosis associated with diabetes; therefore they should be
      based on widely accepted principles as in non-diabetic populations. It seems that
      in DM2 patients the most purposeful strategy could be the popularization of
      healthy attitudes aiming the elimination of unfavorable dietetic and
      environmental factors, such as low physical activity, smoking, and low vitamin D
      intake, as well as education against falls.

PMID- 18615398
TI  - A rare association of hyperparathyroidism and Turner's syndrome--a case report.
AB  - We present the clinical, laboratory, radiological and pathological findings in
      the case and review the literature. Our patient, a 37-year-old woman of short
      stature, was referred because of musculoskeletal pain. After primary evaluation,
      she underwent treatment with calcium and vitamin D supplement with the diagnosis
      of osteomalacia in Turner's syndrome. The rise of serum calcium during medical
      therapy, which was an unusual finding, attracted the clinician's attention to
      another underlying disorder. Further evaluation revealed primary
      hyperparathyroidism due to an adenoma of the parathyroid gland. Even though this
      is a rare diagnosis, its presence should be considered in any patient with
      Turner's syndrome presenting with severe osteoporosis and a rise in serum calcium
      during treatment.

PMID- 18615399
TI  - [131I-MIBG therapy in the treatment of pheochromocytoma in children--own
      experiences].
AB  - Three cases of pheochromocytoma in children/adolescents or young adults treated
      by 131I-MIBG are presented in this study. In one patient 131I-MIBG was
      administrated after ineffective surgical treatment and chemotherapy of a benign
      retroperitoneal tumor, whereas in two other patients 131I-MIBG therapy was
      carried out because of malignant pheochromocytoma dissemination. In a child with
      retroperitoneal paraganglioma decrease of tumor size and its fibrosis after 131I
      MIBG therapy allowed radical surgery and complete recovery. In two other cases
      partial remission was achieved. All patients showed a good subjective response
      with improvement of the general condition and better blood pressure control. In
      two children adverse reactions such as leucopenia, hypothyroidism or hypogonadism
      were observed. The presented data confirm effectiveness and acceptable tolerance
      of 131I-MIBG treatment in pheochromocytoma, what is very important in pediatric
      patients.

PMID- 18615400
TI  - [Acromegaly--from myths to facts].
AB  - The authors present numerous historical descriptions of persons who might
      suffered from gigantism or acromegaly. The oldest medical data of patients,
      initial attempts of causal neurosurgical treatment, history of growth hormone,
      insulin-like growth factor-1, growth hormone releasing hormone and somatostatin
      discovery is reported. The highest contemporary living persons are also listed.

PMID- 18615401
TI  - [New developments in the treatment and monitoring of type 1 diabetes mellitus].
AB  - In recent years, insulin analogues are the benefits of the use in functional
      intensive insulin therapy for the treatment of diabetes. Shortacting insulin
      (lispro, aspart and glulisine) and long-acting insulin (glargine and detemir)
      have been developed for the management of diabetes. Short-acting insulin
      analogues are an alternative to regular human insulin before meals. These new
      short-acting insulin analogues show more rapid onset of activity and a shorter
      duration of action. As a result of these pharmacokinetic differences, an improved
      postprandial glycemic control is achieved, without increasing the risk of
      hypoglycemia. In addition, these insulin analogues can be administered
      immediately before a meal. The long-acting insulin analogues provide basal
      insulin levels for 24 h when administered once (glargine) or two (detemir) daily.
      Compared with previous intermediate- or long-acting conventional insulin, these
      insulins shows a flat profile of plasma insulin levels . The use of these long
      acting insulin analogues appears to be associated with a reduced incidence of
      hypoglycemia, especially at night. The availability of these new insulin
      analogues has the potential to significantly improve long-term control over blood
      glucose in diabetic patients. In recent years more and more frequently the method
      of multiple daily injections (MDI) of insulin is being replaced by the method of
      continuous subcutaneous insulin infusion (CSII). It is the most physiological way
      to administer insulin. In recent years treatment with insulin pumps has been used
      more frequently in the pediatric patients and in the treatment of diabetes in
      pregnancy. Use of continuous glucose monitoring systems enables detection of
      glycemia fluctuations unrevealed by selfmonitoring of blood glucose, such as
      night hypoglycemias and early postprandial hyperglycemias. Real-time systems
      allow to reduce HbA1c levels and limit number of excursions. Non-invasive glucose
      measurement devices are introduced. Fully automated continuous glucose monitoring
      systems integrated with insulin pumps operating in closed-loop model, requiring
      no patient assistance, are still being researched. Commercially available systems
      operate in open-loop model, where the patient has to decide on administration and
      dose of insulin.

PMID- 18615402
TI  - Perspectives on the endocrine society clinical practice guideline for the
      evaluation and treatment of women with hirsutism.

PMID- 18615403
TI  - [Abstracts of the 3rd Polish National Scientific Conference on neuroendocrine
      tumors of the gastroinestinal system and pulmonary endocrine tumors, 2008].

PMID- 18615406
TI  - Dispersion in the Mott insulator UO2: A comparison of photoemission spectroscopy
      and screened hybrid density functional theory.
AB  - We present a comparison between the screened hybrid density functional theory of
      Heyd, Scuseria, and Enzerhof (HSE06) and high-resolution photoemission (PES)
      measurement on a single crystal of UO(2). Angle-resolved photoemission data show
      a slight dispersion in the f-orbital derived bands in good agreement with the HSE
      band structure. The effect of spin-orbit coupling on the HSE band gap has also
      been calculated and found to be negligible.

PMID- 18615407
TI  - Global dynamics and transition state theories: Comparative study of reaction rate
      constants for gas-phase chemical reactions.
AB  - In this review article, we present a systematic comparison of the theoretical
      rate constants for a range of bimolecular reactions that are calculated by using
      three different classes of theoretical methods: quantum dynamics (QD), quasi
      classical trajectory (QCT), and transition state theory (TST) approaches. The
      study shows that the difference of rate constants between TST results and those
      of the global dynamics methods (QD and QCT) are seen to be related to a number of
      factors including the number of degrees-of-freedom (DOF), the density of states
      at transition state (TS), etc. For reactions with more DOF and higher density of
      states at the TS, it is found that the rate constants from TST calculations are
      systematically higher than those obtained from global dynamics calculations,
      indicating large recrossing effect for these systems. The physical insight of
      this phenomenon is elucidated in the present review.

PMID- 18615408
TI  - Regarding paper: "robustness of shrunken predictors in stratified population".

PMID- 18615410
TI  - Controlling the mechanics and nanotopography of biocompatible scaffolds through
      dielectrophoresis with carbon nanotubes.
AB  - Creating a biocompatible carbon-nanotube polymer scaffold is an area that has a
      number of potential applications. Herein, a dielectrophoretic approach was
      pursued to integrate carbon nanotubes into a polymeric material for fabricating a
      nanoscale composite scaffold with increased and controllable mechanical strength.
      The adhesion force, which combines the surface energy of the sample and the
      interfacial energy between the tip and sample, was estimated to be 55.39 +/- 6.72
      nN away from the center of the protrusions at a distance of 0.5 microm while
      being 24.01 +/- 4.45 nN at the center. The adhesion force for the center of the
      cavities was 42.47 +/- 6.91 and 88.21 +/- 15.05 nN at 0.5 microm away from the
      center. NIH 3T3 fibroblast cells were then utilized to test the cellular
      biocompatibility of this multiwalled carbon nanotubes (MWCNTs) film. Cells were
      cultured on the surface and then their attachment, spreading, and proliferation
      behaviors were observed. This nanotube-polymer scaffolding approach has a wide
      range of potential applications including in complex device fabrication as well
      as in developing biomimetic and tissue engineering scaffolds, and artificial
      organs.

PMID- 18615411
TI  - An age-stratified poisson model for comparing trends in cancer rates across
      overlapping regions.
AB  - The annual percent change (APC) has been used as a measure to describe the trend
      in the age-adjusted cancer incidence or mortality rate over relatively short time
      intervals. The yearly data on these age-adjusted rates are available from the
      Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer
      Institute. The traditional methods to estimate the APC is to fit a linear
      regression of logarithm of age-adjusted rates on time using the least squares
      method or the weighted least squares method, and use the estimate of the slope
      parameter to define the APC as the percent change in the rates between two
      consecutive years. For comparing the APC for two regions, one uses a t-test which
      assumes that the two datasets on the logarithm of the age-adjusted rates are
      independent and normally distributed with a common variance. Two modifications of
      this test, when there is an overlap between the two regions or between the time
      intervals for the two datasets have been recently developed. The first
      modification relaxes the assumption of the independence of the two datasets but
      still assumes the common variance. The second modification relaxes the assumption
      of the common variance also, but assumes that the variances of the age-adjusted
      rates are obtained using Poisson distributions for the mortality or incidence
      counts. In this paper, a unified approach to the problem of estimating the APC is
      undertaken by modeling the counts to follow an age-stratified Poisson regression
      model, and by deriving a corrected Z -test for testing the equality of two APCs.
      A simulation study is carried out to assess the performance of the test and an
      application of the test to compare the trends, for a selected number of cancer
      sites, for two overlapping regions and with varied degree of overlapping time
      intervals is presented.

PMID- 18615412
TI  - Bayesian analysis of severe acute respiratory syndrome: the 2003 Hong Kong
      epidemic.
AB  - This paper analyzes data arising from a Severe Acute Respiratory Syndrome (SARS)
      epidemic in Hong Kong in 2003 involving 1755 cases. A discrete time stochastic
      model that uses a back-projection approach is proposed. Markov Chain Monte Carlo
      (MCMC) methods are developed for estimation of model parameters. The algorithm is
      further extended to integrate numerically over unobserved variables of the model.
      Applying the method to SARS data from Hong Kong, a value of 3.88 with a posterior
      standard deviation of 0.09 was estimated for the basic reproduction number. An
      estimate of the transmission parameter at the beginning of the epidemic was also
      obtained as 0.149 with a posterior standard deviation of 0.003. A reduction in
      the transmission parameter during the course of the epidemic forced the effective
      reproduction number to cross the threshold value of one, seven days after control
      interventions were introduced. At the end of the epidemic, the effective
      reproduction number was as low as 0.001 suggesting that the epidemic was brought
      under control by the intervention measures introduced.

PMID- 18615413
TI  - Design of long-term HIV dynamic studies using semiparametric mixed-effects
      models.
AB  - Studies of HIV dynamics in AIDS research are very important in understanding the
      pathogenesis of HIV-1 infection and also in assessing the effectiveness of
      antiviral therapies. There are many AIDS clinical trials on HIV dynamics
      currently in development worldwide, giving rise to many design issues yet to be
      addressed. For example, most studies are focused on short-term viral dynamics and
      the existing models may not be applicable to describe long-term virologic
      response. In this paper, we use a simulation-based approach to study the designs
      of long-term viral dynamics under semiparametric nonlinear mixed-effects models.
      These models not only can preserve the meaningful interpretation of the short
      term HIV dynamics, but also characterize the long-term virologic responses to
      antiretroviral (ARV) treatment. We investigate a number of feasible clinical
      protocol designs similar to those currently used in AIDS clinical trials. In
      particular, we evaluate whether earlier samplings can result in more useful
      information about the viral response trajectory; we also evaluate the
      effectiveness of two strategies: more frequent samplings per subject with fewer
      subjects versus fewer samplings per subject with more subjects while keeping the
      total number of samplings constant. The results of our investigation provide
      quantitative guidance for designing and selecting ARV therapy.

PMID- 18615414
TI  - Energetic nitrogen-rich derivatives of 1,5-diaminotetrazole.

PMID- 18615415
TI  - Phosphorescent, terdentate, liquid-crystalline complexes of platinum(II):
      stimulus-dependent emission.

PMID- 18615416
TI  - Reversible self-assembly of carboxylated peptide-functionalized gold
      nanoparticles driven by metal-ion coordination.
AB  - Carboxylated peptide-functionalized gold nanoparticles (peptide-GNPs) self
      assemble into two- and three-dimensional nanostructures in the presence of
      various heavy metal ions (i.e. Pb(2+), Cd(2+), Cu(2+), and Zn(2+)) in aqueous
      solution. The assembly process is monitored by following the changes in the
      surface plasmon resonance (SPR) band of gold nanoparticles in a UV/Vis
      spectrophotometer, which shows the development of a new SPR band in the higher
      wavelength region. The extent of assembly is dependent on the amount of metal
      ions present in the medium and also the time of assembly. TEM analysis clearly
      shows formation of two- and three-dimensional nanostructures. The assembly
      process is completely reversible by addition of alkaline
      ethylenediaminetetraacetic acid (EDTA) solution. The driving force for the
      assembly of peptide-GNPs is mainly metal ion/carboxylate coordination. The color
      and spectral changes due to this assembly can be used for detection of these
      heavy-metal ions in solution.

PMID- 18615417
TI  - Influence of solvent polarity and hydrogen bonding on the electronic transition
      of coumarin 120: a TDDFT study.
AB  - The characteristics of the electronic transition energy of Coumarin 120 (C120)
      and its H-bonded complexes in various solvents have been examined by time
      dependent density functional theory (TDDFT) in combination with a polarizable
      continuum solvent model (PCM). Molecular structures of C120 and its H-bonded
      complexes are optimized with the B3LYP method in PCM solution, and the dihedral
      angle H14-N13-C7-H15 is dependent on solvent polarity and the type of H-bond. A
      linear correlation of the absorption maximum of C120 with the solvent polarity
      function is revealed with the PCM model for all solvents except DMSO. The
      experimental absorption maximum of C120 in nine solvents is well described by a
      PCM-TDDFT scheme augmented with explicit inclusion of a few H-bonded solvent
      molecules, and quantitative agreement between our calculated results and
      experimental measurements is obtained with an average error of less than 2 nm. H
      bonding at three different sites shifts the absorption wavelength of C120 either
      to the blue or to the red, that is, a significant role is played by solvent
      molecules in the first solvation shell in determining the electronic transition
      energy of C120. The dependence on the H-bonding site and solvent polarity is
      examined by using the Kamlet-Taft equation for solvatochromism.

PMID- 18615418
TI  - Fabrication of ZnO nanowires using nanoscale spacer lithography for gas sensors.

PMID- 18615419
TI  - Quantum chemistry in parallel with PQS.
AB  - This article describes the capabilities and performance of the latest release
      (version 4.0) of the Parallel Quantum Solutions (PQS) ab initio program package.
      The program was first released in 1998 and evolved from the TEXAS program package
      developed by Pulay and coworkers in the late 1970s. PQS was designed from the
      start to run on Linux-based clusters (which at the time were just becoming
      popular) with all major functionality being (a) fully parallel; and (b) capable
      of carrying out calculations on large-by ab initio standards-molecules, our
      initial aim being at least 100 atoms and 1000 basis functions with only modest
      memory requirements. With modern hardware and recent algorithmic developments,
      full accuracy, high-level calculations (DFT, MP2, CI, and Coupled-Cluster) can be
      performed on systems with up to several thousand basis functions on small (4-32
      node) Linux clusters. We have also developed a graphical user interface with a
      model builder, job input preparation, parallel job submission, and post-job
      visualization and display. 

PMID- 18615420
TI  - Modeling the structure-property relationships of nanoneedles: A journey toward
      nanomedicine.
AB  - Innovative biomedical techniques operational at the nanoscale level are being
      developed in therapeutics, including advanced drug delivery systems and targeted
      nanotherapy. Ultrathin needles provide a low invasive and highly selective means
      for molecular delivery and cell manipulation. This article studies the geometry
      and the stability of a family of packed carbon nanoneedles (CNNs) formed by units
      of 4, 6, and 8 carbons, by using quantum chemistry computational modeling
      methods. At the limit of infinite-length, these CNNs might act as semiconductors,
      especially when the number of terminal units is increased. CNNs are also
      potentially able to stabilize ions around their structure. Therefore, due to the
      apolar characteristics of CNNs and their ability to carry ionic species, they
      would be suitable to act as drug carriers through nonpolar biologic media.

PMID- 18615421
TI  - Accelerating molecular dynamic simulation on the cell processor and Playstation
      3.
AB  - Implementation of molecular dynamics (MD) calculations on novel architectures
      will vastly increase its power to calculate the physical properties of complex
      systems. Herein, we detail algorithmic advances developed to accelerate MD
      simulations on the Cell processor, a commodity processor found in PlayStation 3
      (PS3). In particular, we discuss issues regarding memory access versus
      computation and the types of calculations which are best suited for streaming
      processors such as the Cell, focusing on implicit solvation models. We conclude
      with a comparison of improved performance on the PS3's Cell processor over more
      traditional processors.

PMID- 18615422
TI  - A novel method for enzyme design.
AB  - Rational design of enzymes is a stringent test of our understanding of protein
      structure and function relationship, which also has numerous potential
      applications. We present a novel method for enzyme design that can find good
      candidate protein scaffolds in a protein-ligand database based on vector matching
      of key residues. Residues in the vicinity of the active site were also compared
      according to a similarity score between the scaffold protein and the target
      enzyme. Suitable scaffold proteins were selected, and the side chains of residues
      around the active sites were rebuilt using a previously developed side-chain
      packing program. Triose phosphate isomerase (TIM) was used as a validation test
      for enzyme design. Selected scaffold proteins were found to accommodate the
      enzyme active sites and successfully form a good transition state complex. This
      method overcomes the limitations of the current enzyme design methods that use
      limited number of protein scaffold and based on the position of ligands. As there
      are a large number of protein scaffolds available in the Protein Data Band, this
      method should be widely applicable for various types of enzyme design.

PMID- 18615423
TI  - Robust tris-cyclometalated iridium(III) phosphors with ligands for effective
      charge carrier injection/transport: synthesis, redox, photophysical, and
      electrophosphorescent behavior.
AB  - With the target to design and develop new functionalized green triplet light
      emitters that possess distinctive electronic properties for robust and highly
      efficient phosphorescent organic light-emitting diodes (PHOLEDs), a series of
      bluish-green to yellow-green phosphorescent tris-cyclometalated homoleptic
      iridium(III) complexes [Ir(ppy-X)(3)] (X=SiPh(3), GePh(3), NPh(2), POPh(2), OPh,
      SPh, SO(2)Ph, Hppy=2-phenylpyridine) have been synthesized and fully
      characterized by spectroscopic, redox, and photophysical methods. By chemically
      manipulating the lowest triplet-state character of Ir(ppy)(3) with some
      functional main-group 14-16 moieties on the phenyl ring of ppy, a new family of
      metallophosphors with high-emission quantum yields, short triplet-state
      lifetimes, and good hole-injection/hole-transporting or electron
      injection/electron-transporting properties can be obtained. Remarkably, all of
      these Ir(III) complexes show outstanding electrophosphorescent performance in
      multilayer doped devices that surpass that of the state-of-the-art green-emitting
      dopant Ir(ppy)(3). The devices described herein can reach the maximum external
      quantum efficiency (eta(ext)) of 12.3 %, luminance efficiency (eta(L)) of 50.8 cd
      A(-1), power efficiency (eta(p)) of 36.9 Lm W(-1) for [Ir(ppy-SiPh(3))(3)], 13.9
      %, 60.8 cd A(-1), 49.1 Lm W(-1) for [Ir(ppy-NPh(2))(3)], and 10.1 %, 37.6 cd A(
      1), 26.1 Lm W(-1) for [Ir(ppy-SO(2)Ph)(3)]. These results provide a completely
      new and effective strategy for carrier injection into the electrophosphor to
      afford high-performance PHOLEDs suitable for various display applications.

PMID- 18615424
TI  - Quantitative proteomic analysis to discover potential diagnostic markers and
      therapeutic targets in human renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is relatively resistant to chemotherapy and
      radiotherapy. Recent advances in drug development are providing novel agents for
      the treatment of RCC, but the effects are still minimal. In addition, there is an
      urgent need to identify diagnostic markers for RCC. In this report, to discover
      potential diagnostic markers and therapeutic targets, we subjected RCC samples to
      a quantitative proteomic analysis utilizing 2-nitrobenzenesulfenyl (NBS) reagent.
      Proteins were extracted from RCC and adjacent normal tissue, obtained surgically
      from patients, and labeled with NBS reagent containing six (12)C or (13)C. This
      was followed by trypsin digestion and the enrichment of labeled peptides. Samples
      were then subjected to analysis by MALDI-TOF MS. NBS-labeled peptides with a 6 Da
      difference were identified by MS/MS. Thirty-four proteins were upregulated in
      more than 60% of the patients of which some were previously known, and some were
      novel. The identity of a few proteins was confirmed by Western blotting and
      quantitative real time RT-PCR. The results suggest that NBS-based quantitative
      proteomic analysis is useful for discovering diagnostic markers and therapeutic
      targets for RCC.

PMID- 18615425
TI  - Proteomic and transcriptomic study on the action of a cytotoxic saponin
      (Polyphyllin D): induction of endoplasmic reticulum stress and mitochondria
      mediated apoptotic pathways.
AB  - Polyphyllin D (PD) is a potent cytotoxic saponin found in Paris polyphylla. In
      the present study, bioinformatic, proteomic and transcriptomic analyses were
      performed to study the mechanisms of action of PD on human nonsmall cell lung
      cancer (NSCLC) cell line (NCI-H460). Using a gene expression-based bioinformatic
      tool (connectivity map), PD was identified as a potential ER stress inducer. Our
      proteomic and transcriptomic analyses revealed that PD treatment led to
      upregulation of typical ER stress-related proteins/genes including glucose
      regulated protein 78 (BiP/GRP78) and protein disulfide isomerase (PDI). In
      particular, elevated expression of C/EBP homologous transcription factor (chop)
      and activation of caspase-4 occurred at early time point (8 h) of PD treatment,
      signifying an initial ER stress-mediated apoptosis. Induction of tumor suppressor
      p53, disruption of mitochondrial membrane, activation of caspase-9 and caspase-3
      were detected upon prolonged PD treatment. Collectively, these data revealed that
      PD induced the cytotoxic effect through a mechanism initiated by ER stress
      followed by mitochondrial apoptotic pathway. The ability of activating two major
      pathways of apoptosis makes PD an attractive drug lead for anticancer
      therapeutics.

PMID- 18615426
TI  - Validation of reverse phase protein array for practical screening of potential
      biomarkers in serum and plasma: accurate detection of CA19-9 levels in pancreatic
      cancer.
AB  - The current study analyzed reverse phase protein arrays (RPPA) as a means to
      experimentally validate biomarkers in blood samples. One microliter samples of
      sera (n = 71), and plasma (n = 78) were serially diluted and printed on NC-coated
      slides. CA19-9 levels from RPPA results were compared with identical patient
      samples as measured by ELISA. There was a strong correlation between RPPA and
      ELISA (r = 0.87) as determined by scatter plots. Sample reproducibility of CA19-9
      levels was excellent (interslide correlation r = 0.88; intraslide correlation r =
      0.83). The ability of RPPA to accurately distinguish CA19-9 levels between cancer
      and noncancer samples were determined using receiver operating characteristic
      curves and compared with ELISA. The AUC for RPPA and ELISA was comparable (0.87
      and 0.86, respectively). When the mean CA19-9 levels of normal samples was used
      as a cutoff for RPPA and compared with the standard clinical ELISA cutoff,
      comparable specificities (71% for both) were observed. Notably, RPPA samples
      normalized to albumin showed increased sensitivity compared to ELISA (90% vs.
      75%). As RPPA is a high-throughput method that shows results comparable to that
      of ELISA, we propose that RPPA is a viable technique for rapid experimental
      screening and validation of candidate biomarkers in blood samples.

PMID- 18615427
TI  - Rerouting of pyruvate metabolism during acid adaptation in Lactobacillus
      bulgaricus.
AB  - Lactic acid bacteria (LAB) gradually acidify their environment through the
      conversion of pyruvate to lactate, an essential process to regenerate NAD(+) used
      during glycolysis. A clear demonstration of acidification can be found in yogurt,
      the product of milk fermentation by the LAB Lactobacillus delbrueckii ssp.
      bulgaricus (L. bulgaricus) and Streptococcus thermophilus, where the pH falls to
      4.2. Acid adaptation therefore plays an important role in the physiology of LAB.
      Here we present the results of a proteomic approach to reveal cellular changes
      associated with acid adaptation in L. bulgaricus. These results were complemented
      with transcription data for selected genes to show three major effects: (i)
      induction of the chaperones GroES, GroEL, HrcA, GrpE, DnaK, DnaJ, ClpE, ClpP, and
      ClpL, and the repression of ClpC; (ii) induction of genes involved in the
      biosynthesis of fatty acids (fabH, accC, fabI); (iii) repression of genes
      involved in the mevalonate pathway of isoprenoid synthesis (mvaC, mvaS). Together
      with changes in the expression of other genes from the local metabolic network,
      these results for the first time show a coherent picture of changes in gene
      expression expected to result in a rerouting of pyruvate metabolism to favor
      fatty acid biosynthesis, and thereby affect membrane fluidity.

PMID- 18615428
TI  - A novel wavelet-based thresholding method for the pre-processing of mass
      spectrometry data that accounts for heterogeneous noise.
AB  - In recent years there has been an increased interest in using protein mass
      spectroscopy to discriminate diseased from healthy individuals with the aim of
      discovering molecular markers for disease. A crucial step before any statistical
      analysis is the pre-processing of the mass spectrometry data. Statistical results
      are typically strongly affected by the specific pre-processing techniques used.
      One important pre-processing step is the removal of chemical and instrumental
      noise from the mass spectra. Wavelet denoising techniques are a standard method
      for denoising. Existing techniques, however, do not accommodate errors that vary
      across the mass spectrum, but instead assume a homogeneous error structure. In
      this paper we propose a novel wavelet denoising approach that deals with
      heterogeneous errors by incorporating a variance change point detection method in
      the thresholding procedure. We study our method on real and simulated mass
      spectrometry data and show that it improves on performances of peak detection
      methods.

PMID- 18615429
TI  - Comprehensive proteome analysis of Mycobacterium ulcerans and quantitative
      comparison of mycolactone biosynthesis.
AB  - Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rapidly emerging
      human disease in which mycolactone, a cytotoxic and immunosuppressive macrocyclic
      polyketide, is responsible for massive skin destruction. The genome sequencing of
      M. ulcerans has recently been accomplished (http://genolist.pasteur.fr/BuruList/)
      enabling the first proteome study of this important human pathogen. Here, we
      present a comprehensive proteome analysis of different subcellular fractions and
      culture supernatant of in vitro grown M. ulcerans. By a combination of gel-based
      and gel-free techniques for protein and peptide separation with subsequent
      analysis by MS, we identified 1074 different proteins, corresponding to 25% of
      the protein-coding DNA sequence. Interestingly, new information was obtained
      about central metabolism and lipid biosynthesis, and as many as 192 conserved
      hypothetical proteins were found. Comparative analysis of the wild-type strain
      and an isogenic mycolactone-deficient mutant, by 2-DE and iTRAQ labeling of the
      cytoplasmic fraction, revealed differences in the expression profiles of proteins
      involved in lipid metabolism and information pathways, as well as stress
      responses.

PMID- 18615430
TI  - Optimization of evanescent-field fluorescence-assisted lectin microarray for high
      sensitivity detection of monovalent oligosaccharides and glycoproteins.
AB  - Lectin microarray is an emerging technique, which will accelerate glycan
      profiling and discovery of glycan-related biomarkers. One of the most important
      stages in realizing the potential of the technique is to achieve sufficiently
      high sensitivity to detect even the low concentrations of some target
      glycoproteins which occur in sera or tissues. Previously, we developed a lectin
      microarray based on an evanescent-field fluorescence-assisted detection principle
      that allows rapid profiling of glycoproteins. Here, we report optimization of
      procedures for lectin spotting and immobilization to improve the sensitivity and
      reproducibility of the lectin microarray. The improved microarray allows high
      sensitivity detection of even monovalent oligosaccharides that generally have a
      low affinity with lectins (K(d)>10(-6) M). The LOD observed for RCA120, a
      representative plant lectin, with asialofetuin, and an asialo-biantennary N
      glycan probe were determined to be 100 pg/mL and 100 pM, respectively. With the
      improved lectin microarray system, closely related structural isomers, i.e.,
      Le(a) and Le(x), were clearly differentiated by the difference in signal patterns
      on relevant multiple lectins, even though specific lectins to detect these glycan
      structures were not available. The result proved a previously proposed concept of
      lectin-based glycan profiling.

PMID- 18615431
TI  - Chemical proteomic study of isoprenoid chain interactome with a synthetic
      photoaffinity probe.
AB  - A chemical proteomic approach was developed for profiling the noncovalent
      interactome of isoprenoid chain in the yeast proteome. A chemical probe that
      harbors a biotin moiety and a photoreactive benzophenone group linked to the
      terminal of geranyl group was synthesized. Photoaffinity labeling was performed
      by incubating the Saccharomyces cerevisiae proteome and the probe under 365 nm UV
      light. Thirty proteins were identified by immobilized NeutraAvidin enrichment, on
      bead digestion, online 2-D nano-LC/MS/MS identification and semi-quantitative
      proteomic analysis. As noted by Gene Ontology annotation, the identified proteins
      demonstrate a wide range of catalytic activity in several biological processes,
      especially in metabolism and biosynthesis. Further data analysis shows that
      hydrophobic binding of the synthetic probe is potentially the major interaction
      force leading to covalent labeling. These results argue that intracellular
      allosteric interactions conferred by the isoprenoid chain of the corresponding
      chemical structures may be widespread at an interactomic level.

PMID- 18615433
TI  - A parallel affinity purification method for selective isolation of
      polyubiquitinated proteins.
AB  - We developed a parallel affinity purification (PAP) procedure, in which
      ubiquitinated proteins are purified from the cells that coexpress two affinity
      tagged ubiquitins by sequential use of affinity chromatography specific to each
      tag. In contrast with previous procedures using a single affinity-tagged
      ubiquitin, the PAP eliminates highly abundant ubiquitin monomers and
      monoubiquitinated proteins to selectively enrich proteins bearing both affinity
      tags, or poly- and multiubiquitinated proteins. Accordingly, it would serve as a
      powerful method to facilitate mass-spectrometric identification of ubiquitinated
      proteins.

PMID- 18615432
TI  - Separation of phosphoprotein isotypes having the same number of phosphate groups
      using phosphate-affinity SDS-PAGE.
AB  - Herein, we demonstrate the separation of phosphoprotein isotypes having the same
      number of phosphate groups using phosphate-affinity SDS-PAGE. The phosphate
      affinity site is a polyacrylamide-bound Phos-tag that enables the mobility shift
      detection of phosphoproteins from their nonphosphorylated counterparts. As the
      first practical example of the separation, we characterized the
      monophosphorylated Tau isotypes by each of three tyrosine kinases, c-Abl, MET,
      and Fyn. Each monophosphoisotype phosphorylated at the Tyr-394, Tyr-197, or Tyr
      18 was detected as three distinct migration bands. As a further application, we
      extended this technique to the mobility shift analysis of His and Asp
      phosphoisotypes in the Sinorhizobium meliloti FixL/FixJ two-component system.
      FixL is autophosphorylated at the His-285 with ATP, and the phosphate group is
      transferred to the Asp-54 of FixJ and subsequently removed by the FixL
      phosphatase activity. Using this method, we first performed simultaneous
      detection of the phosphorylated and nonphosphorylated isotypes of FixL and FixJ
      generated in their phosphotransfer reaction in vitro. As a result, a
      monophosphoisotype of FixL containing the phosphorylated His residue was
      confirmed. As for FixJ, on the other hand, two monophosphoisotypes were detected
      as two distinct migration bands. One is a well-known isotype phosphorylated at
      the Asp-54. The other is a novel isotype phosphorylated at the His-84.

PMID- 18615434
TI  - Molecular mechanics models for tetracycline analogs.
AB  - Tetracyclines (Tcs) are an important family of antibiotics that bind to the
      ribosome and several proteins. To model Tc interactions with protein and RNA, we
      have developed a molecular mechanics force field for 12 tetracyclines, consistent
      with the CHARMM force field. We considered each Tc variant in its zwitterionic
      tautomer, with and without a bound Mg(2+). We used structures from the Cambridge
      Crystallographic Data Base to identify the conformations likely to be present in
      solution and in biomolecular complexes. A conformational search by simulated
      annealing was undertaken, using the MM3 force field, for tetracycline,
      anhydrotetracycline, doxycycline, and tigecycline. Resulting, low-energy
      structures were optimized with an ab initio method. We found that Tc and its
      analogs all adopt an extended conformation in the zwitterionic tautomer and a
      twisted one in the neutral tautomer, and the zwitterionic-extended state is the
      most stable in solution. Intermolecular force field parameters were derived from
      a standard supermolecule approach: we considered the ab initio energies and
      geometries of a water molecule interacting with each Tc analog at several
      different positions. The final, rms deviation between the ab initio and force
      field energies, averaged over all forms, was 0.35 kcal/mol. Intramolecular
      parameters were adopted from either the standard CHARMM force field, the ab
      initio structure, or the earlier, plain Tc force field. The model reproduces the
      ab initio geometry and flexibility of each Tc. As tests, we describe MD and free
      energy simulations of a solvated complex between three Tcs and the Tet repressor
      protein.

PMID- 18615436
TI  - Facilitated transport of lactic acid in a stirred transfer cell.
AB  - The application of liquid membrane extraction to the recovery of lactic acid from
      model systems and fermentation media was investigated. An experimental study of
      the facilitated transport of lactic acid using ALIQUAT 336 as a mobile carrier in
      a stirred transfer cell is reported. The effect of stirring speed, initial lactic
      acid concentration, carrier concentration, and NaCl as a reagent in the acceptor
      phase are considered. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615437
TI  - A near-infrarod spectroscopy technique for the control of fermentation processes:
      An application to lactic acid fermentation.
AB  - A near-infrared (NIR) spectroscopy technique for the control of lactic acid
      fermentation process has been proposed. Lactic acid, glucose, and biomass
      concentrations were determined by the NIR spectroscopy method. The three
      parameters examined were closely correlated to the results obtained with
      classical laboratory procedures. Moreover, the conditions for the on-line
      utilization of the NIR spectroscopy measurement system were pointed out. The
      great versatility of the NIR spectroscopy should permit its use for other
      fermentation processes. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615438
TI  - Importance of solute partitioning in biphasic oxidation of benzyl alcohol by free
      and immobilized whole cells of pichia pastoris.
AB  - Using free and immobilized whole cells of Pichia pastoris, the biocatalytic
      oxidation of benzyl alcohol was investigated in different two-phase systems. This
      reaction was strongly influenced by both the substrate and product inhibitions,
      and the production rate of benzaldehyde in the aqueous system became maximum at
      the initial substrate concentration of ca. 29 g/L with the aldehyde formation
      less than 4 to 5 g/L even after a longer reaction period. The reaction rates in
      the two-liquid phase systems were predominantly determined by the partitioning
      behaviors of the substrate and product between the two phases rather than by
      enzyme deactivation by the organic solvents. In the two-liquid phase systems,
      consequently, the organic solvent acted as a reservior to reduce these inhibitory
      effects, and it was essential to select the organic solvent providing the optimal
      partitioning of the substrate into the aqueous phase as well as the preferential
      extraction of the product into the organic phase. The whole cells immobilized in
      a mixed matrix composed of silicone polymer [>50% (v/v)] and Ca alginate gel
      (<50%) worked well in the xylene and decane media, providing comparable
      activities with the free cells. The production rate of aldehyde was also
      influenced by the solute partitioning into the hydrophilic alginate phase where
      the cells existed. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615439
TI  - Growth of recombinant fibroblasts in alginate microcapsules.
AB  - To develop a novel strategy of nonautologous somatic gene therapy, we now
      demonstrate the feasibility of culturing genetically modified fibroblasts within
      an immunoprotective environment and the optimal conditions required for their
      continued survival in vitro. When mouse Ltk(-) fibroblasts transfected with the
      human growth hormone gene were enclosed within permselective microcapsules
      fabricated from alginate-polylysine-alginate, they continued to secrete human
      growth hormone at the same rates as the nonencapsulated cells. They also
      continued to proliferate in vitro for at least 1 month even though their
      viability gradually declined to about 50%. The viability can be improved by
      controlling for (a) temperature during encapsulation, (b) duration of treatment
      with polylysine, (c) duration of liquefying the core alginate with sodium
      citrate, and (d) cell density at the time of encapsulation. The best conditions
      leading to improved survival and maximum proliferation of cells within the
      microcapsules were obtained by encapsulating the cells at 4 to 10 degrees C
      instead of room temperature, coating the microspheres with polylysine for 6 to 10
      min instead of 20 min, liquefying the core alginate by treating with citrate for
      20 min instead of 6 to 10 min, and using a concentration of 2 x 10(6) cells/mL of
      alginate for encapsulation. Under such conditions, normally adherent and
      genetically engineered mouse fibroblasts survived and proliferated optimally
      within the microcapsule environment. The encapsulated fibroblasts maintained
      their level of transgene expression while recombinant gene products such as human
      growth hormone could diffuse through the microcapsule membrane without
      impediment. The demonstration that genetically modified fibroblasts can survive
      and continue to deliver recombinant gene products from within these microcapsules
      and the optimization for their maximal viability and growth within microcapsules
      should increase the potential for success in using such microencapsulated
      recombinant cells for somatic gene therapy. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615440
TI  - Blueprint for a lipase support: Use of hydrophobic controlled-pore glasses as
      model systems.
AB  - For the commercial exploitation of lipase biocatalysis to be successful, it is
      essential that effective supports are selected for lipase immobilization. In this
      study hydrophobic controlled-pore glasses have been used as model systems for the
      immobilization of Rhizomucor miehei lipase. The effect of pore diameter and
      surface chemistry on enzyme efficiency in a typical esterification reaction under
      essentially nonaqueous conditions has been examined. It has been found that pore
      diameters of at least 35 nm are needed for the lipase to be able to utilize the
      internal volume of the support particles in the immobilization process. Despite
      the small size of the substrates in the esterification reaction, even larger
      pores (>100 nm) are required for the lipase efficiency to become independent of
      pore diameter; below 100 nm lipase activity and efficiency are markedly reduced.
      It has also been shown that the chemical nature of the hydrophobic surface plays
      an important part in catalyst design. Although lipase will adsorb readily to a
      wide range of hydrophobic groups, the highest catalyst activities are obtained
      when the glass surface is derivatized to give long alkyl chains; the presence of
      unsaturated derivatives gonerally leads to a reduction in activity. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18615441
TI  - Kinetics of adhesion and spreading of animal cells.
AB  - The adhesion and spreading of cells at surfaces are well established phenomena
      which have been extensively observed using light or electron microscopy. The
      kinetics of both processes can be quantitatively measured by allowing the cells
      to attach themselves to the surface of a planar waveguide allows the number of
      cells per unit area and a parameter uniquely characterizing their shape, such as
      the area in contact with the surface, to be determined. Cells suspended in
      nutrient medium or pure phosphate buffer were allowed to attach to and spread on
      a metal oxide surface or a layer of fibronectin, and the kinetics of attachment
      and spreading have been measured. Attachment kinetics are the same in all cases,
      but spreading on the metal oxide requires nutrient medium, without which it does
      not occur. Spreading of cells attached to a layer of fibronectin in the absence
      of nutrient medium occurs at about a tenth of the rate of cells spreading on
      metal oxide in the presence of nutrient. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615442
TI  - Biodegradation of pesticides in nonionic water-in-oil microemulsions of tween 85:
      Relationship between micelle structure and activity.
AB  - Water-in-oil microemulsion systems have been studied in recent years for a number
      of applications in protein separation and enzymology. Although it is well
      established that reversed micelle systems provide an excellent medium for
      nonaqueous biocatalytic studies, there is still much speculation as to the
      interaction of the enzyme with the surfactant interface. Polyoxyethylene sorbitan
      trioleate (Tween 85) is a nonionic surfactant which has some interesting
      properties for microemulsion formation and protein solubilization. In conjunction
      with a separate article describing the structural features of Tween 85 reversed
      micelles in hexane with isopropanol as a cosurfactant, this work describes the
      activity of an enzyme, organophosphorus hydrolase, for degrading organophosphorus
      pesticides in this microemulsion system. Ternary phase diagrams were constructed
      to outline the phase boundaries at different temperatures and isopropanol
      concentrations, which elucidate the role of the cosurfactant alcohol, as well as
      some features of micelle structure. Kinetic and stability studies with
      organophosphorus hydrolase show the effect of enzyme partitioning between the
      micelle surfactant layer and aqueous core. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615443
TI  - Effect of solution pH and ionic strength on the separation of albumin from
      immunoglobulins (IgG) by selective filtration.
AB  - Although protein fractionation by selective membrane filtration has numerous
      potential applications in both the downstream processing of fermentation broths
      and the purification of plasma proteins, the selectivity for proteins with only
      moderately different molecular weights has generally been quite poor. We have
      obtained experimental data for the transport of bovine serum albumin (BSA) and
      immunoglobulins (IgG) through 100,000 and 300,000 molecular weight cutoff
      polyethersulfone membranes in a stirred ultrafiltration device at different
      solution pH and ionic strength. The selectivity was a complex function of the
      flux due to the simultaneous convective and diffusive solute transport through
      the membrane and the bulk mass transfer limitations in the stirred cell. Under
      phsioligical conditions (pH 7.0 and 0.15 M NaCI) the maximum selectivity for the
      BSA-IgG separation was only about 2.0 due primarily to the effects of protein
      adsorption. In contrast, BSA-IgG selectivities as high as 50 were obtained with
      the same membranes when the protein solution was at pH 4.8 and 0.0015 M NaCl.
      This enhanced selectivity was a direct result of the electrosatatic contributions
      to both bulk and membrane transport. The membrane selectivity could actually be
      reversed, with higher passage of the larger IgG molecules, by using a 300,000
      molecular weight cutoff membrane at pH 7.4 and an ionic strength of 0.0015 M
      NaCl. These results clearly demonstrate that the effectiveness of selective
      protein filtration can be dramatically altered by appropriately controlling
      electrostatic interactions through changes in pH and/or ionic strength. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18615444
TI  - Extraction of rIL-2 inclusion bodies from Escherichia coli using cross-flow
      filtration.
AB  - A cross-flow membrane filtration process was developed for the recovery of rIL-2
      inclusion bodies from homogenized Escherichia coli. The membrane extraction
      process was comprised of a two-step diafiltration followed by an extraction with
      7 M GuHCl and a 40-fold dilution of the solubilized inclusion bodies into 0.01 M
      Tris-HCl, 0.035 M NaCl, pH 7.9. The first diafiltration was with a 0.03 M Tris
      HCl, 5 mM ethylenediaminetetraacetic acid (EDTA), pH 8, followed by a
      diafiltration with 1.75 M GuHCl. All of the insoluble rIL-2 was retained behind
      the membrane, whereas a GuHCl wash solubilized approximately 15% of the rIL-2.
      The membrane process increased the yield of rIL-2 in the diluted extract by
      threefold as compared to a similar centrifuge process with a significant increase
      in purity as determined by reverse-phase high-performance liquid chromatography
      (HPLC). (c) 1994 John Wiley & Sons, Inc.

PMID- 18615445
TI  - Pervaporative butanol fermentation by Clostridium acetobutylicum B18.
AB  - Extractive acetone-butanol-ethanol (ABE) fermentation was carried out
      successfully using pervaporation and a low-acid-producing Clostridium
      acetobutylicum B18. A pervaporation module with 0.17 m(2) of surface area was
      made of silicone membrane of 240 mum thickness. Pervaporation experiments using
      make-up solutions showed that butanol and acetone fluxes increased linearly with
      their concentrations in the aqueous phase. Fickian diffusion coefficients were
      constants for fixed air flow rates, and increased at higher sweep air flow rates.
      During batch and fed-batch fermentations, pervaporation at an air flow rate of 8
      L/min removed butanol and acetone efficiently. Butanol concentration was
      maintained below 4.5 g/L even though Clostridium acetobutylicum B18 produced
      butanol steadily. Pervaporation could not remove organic acids efficiently, but
      organic acids did not accumulate because strain B18 produced little organic acid
      and recycled added organic acids efficiently. With pervaporation, glucose
      consumption rate increased compared to without pervaporation, and up to 160 g/L
      of glucose was consumed during 80 h. Cell growth was not inhibited by possible
      salt accumulation or oxygen diffusion through the silicone tubing. The culture
      volume was maintained relatively constant during fed-batch operation because of
      an offsetting effect of water and product removal by pervaporation and addition
      of nutrient supplements. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615446
TI  - Polymer-polymer organic solvent two-phase system: A new type of reaction medium
      for bioorganic synthesis.
AB  - Mixing solutions of polymers dissolved in chloroform resulted in turbid solutions
      that parted into two separate phases upon standing. Each phase consisted
      primarily of one of the two polymers and contained only small amounts of the
      other. An enzyme (alpha-chymotrypsin) added to the two-phase system partitioned
      preferentially to one of the phases; this was observed with native enzyme and
      with enzyme associated with one of the polymers through non-convalent
      interactions. Under the conditions studied, alpha-chymotrypsin was active and
      expressed even higher activity and stability than native enzyme added to the
      organic solvent without polymer. An emulsion was easily formed on mixing with
      small droplets of one of the phases suspended in the other phase. By operating
      with the enzyme in the emulsion, a very attractive system for carrying out enzyme
      catalyzed conversions was created. Short diffusion distances and minimized steric
      hindrance are two characteristics of such systems. At the conclusion of the
      reaction, stirring/mixing was ceased and, after phase separation, it was possible
      to recover the enzyme as well as the product, under ideal conditins, from
      different phases. The enzyme was then reused. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615447
TI  - Fed-batch operation of recombinant Escherichia coli containing trp promoter with
      controlled specific growth rate.
AB  - A feb-batch operation for the production of bovine somatotropin (bST) under the
      control of tryptophan promoter in Escherichia coli was investigated. The plasmid
      used contains a two-cistron system and altered codon usage for higher expression
      of bST. Specific growth rate is an important parameter in the fermentation,
      because it affects the production of growth-inhibitory organic acids and the
      expression of recombinant protein. The feeding rate was adjusted to keep the
      specific growth rate constant in this study. The variable growth yield expressed
      as a function of time was used for the calculation of the feeding rate. The
      growth yield decreases during the fermentation as product expression is induced.
      The specific growth rate was well controlled; however, intracellular bST
      concentration decreased at high cell concentrations. This is considered to be due
      to degradation by proteases. The decrease was prevented by an exponential feeding
      of the yeast extract as an organic nitrogen source. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615448
TI  - Depressive symptoms and suicidal ideation among older adults receiving home
      delivered meals.
AB  - OBJECTIVE: Homebound older adults may be vulnerable to the deleterious impact of
      untreated depression. Yet because these elders are difficult to reach, there is
      little data on the rates of depressive symptoms and suicidal ideation among this
      group. The objective of this study is to document the rates of depression and
      correlates among a population of homebound elders. METHODS: Using a community
      based participatory research partnership, we implemented a routine screening for
      depressive symptoms and suicidal ideation among older recipients of Westchester
      County's home meal program. Older adults enrolled in the home delivered meal
      program were administered the Physician Health Questionnaire-9 (PHQ-9), and
      questions to assess pain, falls, alcohol abuse and perceived emotional distress.
      RESULTS: In our sample of 403 meal recipients, 12.2% of older adults reported
      clinically significant depression (PHQ-9 > 9) and 13.4% reported suicidal
      thoughts. One-third of recipients with significant depressive symptoms were
      currently taking an antidepressant. Almost one-third of older adults who endorsed
      suicide ideation did not report clinically significant depressive symptoms. Among
      men, suicidal thoughts were associated with chronic pain and greater depression
      severity, whereas pain was not a predictor of suicidal thoughts among women.
      CONCLUSION: More than one in nine elders suffer from depression; most are
      untreated with one-third undertreated. Through partnerships between public
      agencies that provide age related services and academic investigators there is an
      opportunity for improved detection of unmet mental health needs. Future research
      should explore innovative models to improve access to mental health services once
      unmet need is detected.

PMID- 18615449
TI  - Adenovirus-mediated inhibition of SPARC attenuates liver fibrosis in rats.
AB  - BACKGROUND: The interaction between fibrogenic cells and extracellular matrix
      plays a role in liver fibrosis, yet the mechanisms are largely unknown. Secreted
      protein, acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that
      is expressed by hepatic stellate cells and is overexpressed in fibrotic livers.
      We investigated the in vivo role of SPARC in experimentally induced liver
      fibrosis in rats. METHODS: A recombinant adenovirus carrying antisense SPARC was
      constructed (AdasSPARC). Advanced liver fibrosis was induced in Sprague-Dawley
      rats by prolonged intraperitoneal administration of thioacetamide. Animals
      received injections of AdasSPARC or Ad beta gal (control adenovirus) via the tail
      vein and directly into the liver 1 week after the first dose. The pathological
      changes in liver tissues and indices of fibrosis were assessed at eight weeks.
      Expression of SPARC, transforming growth factor (TGF)-beta and alpha-smooth
      muscle actin were evaluated by quantitative real-time polymerase chain reaction,
      western blotting, enzyme-linked immunosorbent assay and immunohistochemistry.
      RESULTS: Hepatic SPARC expression significantly increased during the development
      of liver fibrosis. AdasSPARC markedly attenuated the development of hepatic
      fibrosis in rats treated with thiocetamide, as assessed by decreased collagen
      deposition, lower hepatic content of hydroxyproline and less advanced
      morphometric stage of fibrosis. AdasSPARC treatment reduced inflammatory activity
      (Knodell score) and suppressed transdifferentiation of hepatic stellate cell to
      the myofibroblasts like phenotype in vivo. Furthermore, in vitro inhibition of
      SPARC on hepatic stellate cells decreases the production of TGF-beta.
      CONCLUSIONS: This is the first study to demonstrate that knockdown of hepatic
      SPARC expression ameliorates thioacetamide-induced liver fibrosis in rats with
      chronic liver injury. SPARC is a potential target for gene therapy in liver
      fibrosis.

PMID- 18615450
TI  - Compound heterozygosity of non-deletional hereditary persistence of fetal
      hemoglobin and deltabeta-thalassemia.

PMID- 18615451
TI  - Prospects and perils of retrospective risk assessment of erythropoiesis
      stimulating agents.

PMID- 18615452
TI  - The association between non-Hodgkin lymphoma and renal cell carcinoma in an HIV
      positive patient: clinico-pathological features and pathogenic implications.

PMID- 18615454
TI  - Notice of retraction. Alteration of p73 in acute myelogenous leukemia.

PMID- 18615455
TI  - Correlation between chemical and solid-state structures and enzymatic hydrolysis
      in novel biodegradable polyesters. The case of poly(propylene
      alkanedicarboxylate)s.
AB  - A series of seven fast-biodegrading aliphatic polyesters were prepared from 1,3
      propanediol and aliphatic diacids with increasing number of methylene units (x).
      Melting points decreased from PPSu to PPAd and then increased again to PPAz and
      PPSeb. Crystallization rates and thermal stability increased steadily with
      increasing x. Glass transition temperatures decreased steadily to PPPim and
      subsequently increased. Enzymatic degradation of the polymers in the presence of
      a mixture of Rhizopus delemar and Pseudomonas cepacia lipases was much faster
      than that of poly(epsilon-caprolactone). All the polyester specimens were almost
      disintegrated within 36 h. PPSub exhibited the fastest enzymatic hydrolysis
      rates, PPAd and PPSuc the slowest.

PMID- 18615456
TI  - Nanocomposites of genipin-crosslinked chitosan/silver nanoparticles--structural
      reinforcement and antimicrobial properties.
AB  - This study investigates the feasibility of a novel nanocomposite (GC/Ag) of a
      genipin-crosslinked chitosan (GC) film in which was embedded various amounts of
      Ag nanoparticles for wound-dressing applications. In situ UV-vis results revealed
      that adding chitosan solution did not affect the characteristics of Ag
      nanoparticles. The water uptake ratios and surface hydrophilicity of the GC/Ag
      nanocomposite were better and the degradation rates slightly lower than those of
      the pure GC film. The presence of Ag nanoparticles enhanced L929 cell attachment
      and growth. Its function as an anti-microbial agent in a GC/Ag nanocomposite was
      assessed for Ag contents of over 100 ppm. In conclusion, silver ions had dual
      functions--structural reinforcement and provision of antimicrobial properties to
      a biocompatible polymer.

PMID- 18615457
TI  - Advanced semiconductor diagnosis by multidimensional electron-beam-induced
      current technique.
AB  - We present advanced semiconductor diagnosis by using electron-beam-induced
      current (EBIC) technique. By varying the parameters such as temperature,
      accelerating voltage (V(acc)), bias voltage, and stressing time, it is possible
      to extend EBIC application from conventional defect characterization to advanced
      device diagnosis. As an electron beam can excite a certain volume even beneath
      the surface passive layer, EBIC can be effectively employed to diagnose
      complicated devices with hybrid structure. Three topics were selected to
      demonstrate EBIC applications. First, the recombination activities of grain
      boundaries and their interaction with Fe impurity in photovoltaic
      multicrystalline Si (mc-Si) are clarified by temperature-dependent EBIC. Second,
      the detection of dislocations between strained-Si and SiGe virtual substrate are
      shown to overcome the limitation of depletion region. Third, the observation of
      leakage sites in high-k gate dielectric is demonstrated for the characterization
      of advanced hybrid device structures.

PMID- 18615459
TI  - Peaceful post-conflict interactions between aggressors and bystanders in captive
      lowland gorillas (Gorilla gorilla gorilla).
AB  - We observed a colony of lowland gorillas in order to assess the occurrence of
      Peaceful Post-Conflict Interactions between Aggressors and Bystanders (PPIAB). We
      compared the dynamics of PPIAB with those of Peaceful Post-Conflict Interactions
      between Victims and Bystanders (PPIVB), which are directed toward victims. We
      confirmed the occurrence of PPIAB (mean Triadic Contact Tendency: 41.7%+/-16.2%
      SEM) at frequencies comparable to PPIVB. Immature gorillas were responsible for
      most PPIAB. PPIAB occurred when the bystander was unrelated to either the
      aggressor or the victim, and when it was a relative of the aggressor. However,
      affinitive contact rates were higher in the former case. Unlike PPIVB, PPIAB
      significantly reduced the likelihood of further aggressions within the group,
      suggesting that they work at an immediate level. Our data also suggest that
      bystanders decide when a peaceful contact may be too risky; in fact, neither
      PPIAB nor PPIVB occurred after high-intensity aggressions.

PMID- 18615458
TI  - Androgen-dependent activation of human cytomegalovirus major immediate-early
      promoter in prostate cancer cells.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) major immediate early (MIE) promoter,
      which is involved in viral reactivation, is specifically activated by androgen in
      LNCaP prostate cancer cells. METHODS: Androgen-dependent transcriptional
      activities of the HCMV MIE promoter were measured by transient transfection
      assay. Expression levels of genes related to protein kinase A (PKA)-signaling
      pathway was measured by RT-PCR. RESULTS: Activation of the HCMV MIE promoter by
      androgen results from an increase in PKA activities. The expression level of PKA
      catalytic (C) subunit beta transcript variant 2 (PKA-C beta 2) was decreased by
      serum deprivation and was increased by R1881 treatment, in a pattern similar to
      changes of the HCMV MIE promoter activities. Furthermore the exogenous expression
      of PKA-C beta 2 strongly activated the HCMV MIE promoter, indicating that
      regulation of the PKA-C beta 2 expression might be a direct upstream factor in
      the HCMV MIE promoter regulation by androgen in LNCaP cells. CONCLUSIONS: The
      data elucidated the mechanisms by which androgen activates PKA in androgen
      dependent prostate cancer cells, resulting in activation of the HCMV MIE
      promoter. These results support the possibility that activation of the HCMV MIE
      promoter by androgen in the prostate could cause the productive infection, which
      might contribute to oncomodulation in prostate cancers.

PMID- 18615460
TI  - Food transfer in common marmosets: parents change their tolerance depending on
      the age of offspring.
AB  - Food transfer is considered to provide infants with additional nutrients during
      weaning, and in fact, its frequency peaks around this time. However, the
      mechanisms underlying such food transfer remain unclear. In this study, we
      investigated whether adult common marmosets (Callithrix jacchus) change their
      tolerance to offspring begging for food depending on the offspring's age. We used
      four families consisting of breeding pairs, older offspring (29-49 weeks old),
      and younger offspring (7-15 weeks old). To directly compare the responses of a
      parent with its older and younger offspring, we placed one parent and one
      offspring in a testing space at one time. We presented foods where only the
      parent could reach them to ensure that the foods were transferred from the parent
      to offspring. Younger offspring showed more interest in food being held by the
      parents than older offspring. Parents refused older offspring more frequently
      than younger offspring and transferred food more often to younger offspring than
      to older offspring. There was no difference in all behavioral categories between
      fathers and mothers. These results suggest that both fathers and mothers are more
      tolerant to weanlings, but their tolerance decreases as offspring mature.

PMID- 18615461
TI  - Angioarchitecture of the ventral surface of the tongue from Wistar rats.
AB  - The goal of this study was to describe the angioarchitecture of the ventral
      surface of the tongue from Wistar rats using a vascular corrosion casting
      technique associated with scanning electron microscopy (SEM). Six Wistar rats
      were used for the vascular casting method with Mercox resin. Following the resin
      polymerization, the tongue of each animal was dissected and corroded in a 5%
      sodium hydroxide solution. Once the corrosion and drying of the specimens were
      completed, the specimens were mounted on aluminum stubs, coated with carbon and
      gold and analyzed under SEM. The results showed that the ventral surface of the
      tongue presents simple, even and abundant vasculature constituted by a vascular
      plexus consisting of a superficial vascular network and by the ranine veins. The
      superficial vascular network, made up of the ascending and descending branches,
      presents as a loose network, with little morphological variation between the
      capillary loops.

PMID- 18615462
TI  - The acute temperature tolerance of green sturgeon (Acipenser medirostris) and the
      effect of environmental salinity.
AB  - We investigated the effect of environmental salinity on the upper thermal
      tolerance of green sturgeon (Acipenser medirostris), a threatened species whose
      natural habitat is vulnerable to temperature and salinity variation as a result
      of global climate change. Freshwater (FW)-reared sturgeon were gradually
      acclimated to salinities representing FW, estuary water (EST), or San Francisco
      Bay water (BAY) at 18 degrees C, and their critical thermal maximum (CTMax) was
      measured by increasing temperature 0.3 degrees C/min until branchial ventilation
      ceased. CTMax was 34.2+/-0.09 degrees C in EST-acclimated fish, with FW- and BAY
      acclimated fish CTMax at 33.7+/-0.08 and 33.7+/-0.1 degrees C, respectively.
      Despite the higher CTMax in EST-acclimated fish, FW-acclimated sturgeon
      ventilation rate reached a peak that was 2 degrees C higher than EST- and BAY
      acclimated groups and had a greater range of temperatures within which they
      exhibited normal ventilatory function as assessed by Q10 calculation. The
      osmoregulatory consequences of exposure to near-lethal temperatures were assessed
      by measuring plasma osmolality and hematocrit, as well as white muscle, brain,
      and heart tissue water contents. Hematocrit was increased following CTMax
      exposure, most likely owing to the elevated metabolic demands of temperature
      increase, and plasma osmolality was significantly increased in EST- and BAY
      acclimated fish, which was likely the result of a greater osmotic gradient across
      the gill as metabolism increased. To our knowledge, this represents the first
      evidence for an effect of salinity on the upper thermal tolerance of sturgeon, as
      well as the first investigation of the osmoregulatory consequences of exposure to
      near-lethal temperatures.

PMID- 18615463
TI  - The influence of Young's modulus of loaded implants on bone remodeling: an
      experimental and numerical study in the goat knee.
AB  - The aim of this study was to examine the influence of the Young's modulus of the
      implant material on the bone remodeling in a loaded condition. A combined animal
      experimental and computational study was set up. The animal experimental group
      comprised of 16 Saanen goats, each receiving one titanium implant (Young's
      modulus 110 GPa) and one high-density polyethylene (HDPE) implant (Young's
      modulus 1 GPa) in the left femoral condyle. Both types of implants received a
      titanium coating of 100 nm thickness. The implants protruded in the knee joint
      space and were directly weight bearing. The first group of eight goats was
      sacrificed after 6 weeks of loading and the second group of eight goats after 6
      months of loading. The 16 femoral condyles with the 32 implants were prepared for
      microfocus computed tomography (micro-CT) scanning and histological sectioning.
      Three-dimensional trabecular bone parameters were calculated on the micro-CT
      images for the zones neck, middle, and apex of the implant. The percent of bone
      contact with the implant was measured on longitudinal histological sections. An
      axisymmetric finite element (FE) model was created to compare peri-implant bone
      strains and relative motion between a titanium and a HDPE implant for the
      experimental loading condition, and to assess the influence of different bone
      implant interface (contact) conditions. From the statistical analysis of the 3D
      bone parameters, the difference between the titanium and HDPE implants was not
      significantly different (p > 0.05) between the zones (neck, middle, and apex) for
      both groups of goats. The implants could be considered in their entirety. After 6
      weeks of loading, the PE implant presented lower connectivity and smaller marrow
      spaces in the circular region of 0-500 microm. In the region 500-1500 microm more
      bone volume was present for the PE implant. After 6 months, the PE implants
      showed more bone volume and thicker trabeculae than the titanium implants for the
      entire length of the implant. This effect was already present in the smallest
      region of interest, 0-500 microm. After 6 months more fibrous encapsulation was
      found around titanium implants. FE results demonstrated a substantial influence
      of the interface conditions on peri-implant strains and relative motion. For
      interface conditions that were representative for the early postoperative
      situation (involving press-fit and friction), differences in peri-implant bone
      strain distributions between titanium and HDPE could be related to the
      experimentally observed differences in amounts of bone and fibrous encapsulation.
      In contrast, differences in relative motion did not seem to play a role. Both the
      experimental and computational results suggest that implant stiffness can affect
      the peri-implant tissue response, which may be related to differences in peri
      implant strains.

PMID- 18615464
TI  - Synthesis, characterization, and biocompatibility of novel injectable,
      biodegradable, and in situ crosslinkable polycarbonate-based macromers.
AB  - A series of novel self-crosslinkable and biodegradable polymers,
      poly(hexamethylene carbonate-fumarate) and poly(hexamethylene carbonate)
      diacrylate, and their amphiphilic copolymers with polyethylene glycol,
      poly(ethylene glycol fumarate-co-hexamethylene carbonate-fumarate) (PEGF-co
      PHMCF), were developed for tissue engineering using propylene oxide as an acid
      scavenger. The synthesized polymers are white, which makes them more suitable for
      self-crosslinking via photopolymerization. These novel polymers were fully
      characterized using nuclear magnetic resonance spectroscopy, Fourier-transform
      infrared spectroscopy, gel permeation chromatography, differential scanning
      calorimetry, and rheometry. The cytocompatibility of the photocrosslinked
      networks were evaluated by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] assay. These polymers can be used as precursors to prepare polymer
      networks and scaffolds with controlled hydrophilicity, biodegradability, and
      mechanical characteristics. Results obtained suggest that these polymers are
      potentially useful as injectable and photocrosslinkable materials for cell
      delivery, tissue engineering, and drug delivery applications.

PMID- 18615465
TI  - Pulsed electric field as a potential new method for microbial inactivation in
      scaffold materials for tissue engineering: the effect on collagen as a scaffold.
AB  - Hybrid scaffolds for tissue engineering are becoming increasingly complex through
      incorporation of biologically active biomacromolecules. There is a need to
      develop a compatible sterilization method that is capable of killing
      microorganisms, without adversely affecting the labile scaffold biomaterials or
      biomacromolecular components. Pulsed electric field (PEF) treatment has been
      successful as a nonthermal microbial inactivation-pasteurization method within
      the food industry. We have previously demonstrated that PEF treatment inactivates
      E. coli seeded in collagen gels. Here, we show that PEF treatment does not affect
      the structural integrity of the collagen molecule or its adsorption to
      polystyrene and hydroxyapatite surfaces. Moreover, osteoblast cells cultured on
      PEF-treated collagen, which was coated onto two- and three-dimensional scaffolds,
      retained their normal morphology, growth rate, and functionality. PEF treatment,
      therefore, shows great potential to be used as a sterilization method for
      collagen-based biomaterials.

PMID- 18615466
TI  - Regional variations in the viscoelastic compressive properties of the
      temporomandibular joint disc and implications toward tissue engineering.
AB  - Evidence from experimental and finite element studies have shown that the
      temporomandibular joint disc is heavily loaded during normal physiological
      function. Several studies have been carried out to investigate the response of
      the disc to tensile and static compressive forces. However, there is limited
      information that elucidates the dynamic characteristics of the disc under in vivo
      loading conditions. These investigations assessed the effect of physiologically
      relevant applied strain amplitudes and frequencies to determine regional
      mechanical properties of the disc. Cyclic tests on porcine TMJ discs were carried
      out over a period of 15 cycles, and the resultant compressive moduli and energy
      dissipation properties of the disc were reported. Results showed that modulus
      values were more dependent on strain amplitude than on frequency, and modulus
      values exhibited a strong regional variation. Clear hysteresis loops were evident
      in each set of testing parameters, and the only statistically significant
      regional variation in energy dissipation was between the central and medial
      regions. From these investigations, a more detailed understanding of the spatial
      mechanical properties of the TMJ disc has been achieved under physiologically
      relevant loading conditions. Combined with studies on other loading modalities of
      the disc, these results will serve as a benchmark for future TMJ disc tissue
      engineering endeavors.

PMID- 18615467
TI  - Cellular responses to degradable cyclic acetal modified PEG hydrogels.
AB  - In this study, high viability of bone marrow stromal stem cells (BMSCs)
      encapsulated in a synthetic, poly[poly(ethylene glycol)-co-cyclic acetal] (PECA)
      hydrogel has been reported. This novel degradable hydrogel, which contains cyclic
      acetal as degradable segments and poly(ethylene glycol) (PEG) as hydrophilic
      segments, has been designed to limit the release of acidic products during
      hydrolytic degradation. PECAs with three different molecular weights (PECA 600,
      1000, and 2000) were prepared to evaluate the effect of polymer main chain
      molecular weight on the viability and morphology of BMSCs embedded in PECA
      hydrogels as well as the viability of BMSCs exposed to PECA degradation products.
      Results demonstrated high BMSC viability when incubated in control media with
      PECA, while a significant decrease in viability was noted after 4 days when
      incubated in media augmented with PEG diacrylate. There was no effect of PECA
      molecular weight on the differentiation and cytotoxicity of degradation products
      up to 4 days, indicating that the degradation products' terminal carbonyl groups
      do not significantly affect cell viability and differentiation. BMSC viability
      when embedded on PECA hydrogels was evaluated by a LIVE/DEAD assay, and confirmed
      high viability up to 14 days. Gene expression analysis confirmed that BMSCs
      embedded in PECA hydrogels undergo osteogenic differentiation. Histological
      analysis also showed that cell morphology was significantly influenced by
      hydrogel swelling degree, which is itself controllable by the molecular weights
      of PECA main chains. These results indicate that PECA hydrogels may be utilized
      as scaffolds for regeneration of bone-like tissues.

PMID- 18615468
TI  - Tissue response and orbital floor regeneration using cyclic acetal hydrogels.
AB  - Orbital floor injuries are a common form of traumatic craniofacial injury that
      may not heal properly through the body's endogenous response. Reconstruction is
      often necessary, and an optimal method does not exist. We propose a tissue
      engineering approach for orbital bone repair based upon a cyclic acetal
      biomaterial formed from 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane
      2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The EHD
      monomer and PEGDA polymer may be fabricated into an EH-PEG hydrogel by radical
      polymerization. The objectives of this work were to study (1) the tissue response
      to EH-PEG hydrogels in an orbital bone defect and (2) the induction of bone
      formation by delivery of bone morphogenetic protein-2 (BMP-2) from EH-PEG
      hydrogels. EH-PEG hydrogels were fabricated and implanted into an 8-mm rabbit
      orbital floor defect. Experimental groups included unloaded EH-PEG hydrogels, and
      EH-PEG hydrogels containing 0.25 microg and 2.5 microg BMP-2/implant. Results
      demonstrated that the unloaded hydrogel was initially bordered by a fibrin clot
      and then by fibrous encapsulation. BMP-2 loaded EH-PEG hydrogels, independent of
      concentration, were surrounded by fibroblasts at both time points. Histological
      analysis also demonstrated that significant bone growth was present at the 2.5
      microg BMP-2/implant group at 28 days. This work demonstrates that the EH-PEG
      construct is a viable option for use and delivery of BMP-2 in vivo.

PMID- 18615469
TI  - Novel apatite fiber scaffolds can promote three-dimensional proliferation of
      osteoblasts in rodent bone regeneration models.
AB  - We have successfully synthesized hydroxyapatite fibers via a homogenous
      precipitation method. Using these hydroxyapatite fibers, we have produced the
      apatite fiber scaffolds (AFS) with well-controlled pore sizes (porosity above
      95%). The AFS is relatively simple to synthesize, and its porosity and pore size
      are controllable. The usefulness of AFS as a scaffold for bone regeneration was
      evaluated by (1) seeding and culturing cells in the AFS in vitro, (2) implanting
      the AFS seeded with cells inside the subcutaneous tissue of mice. The AFS had
      biocompatibility to support cell adhesion, proliferation, and differentiation.
      Ectopic bone formation could be formed in the AFS at 12 weeks after implantation
      into the subcutaneous tissue. Because of its high interpore connection, pore
      diameters, and porosity, it was believed that AFS was an effective scaffold that
      provided a three-dimensional cell culture environment. In both in vitro and in
      vivo environments, the more porous AFS was more advantageous in cell
      proliferation, cell adhesion, proliferating capacity, robust cell
      differentiation, ultimately inducing bone ingrowth inside the scaffolds.

PMID- 18615470
TI  - In vitro osteogenic potential of human bone marrow stromal cells cultivated in
      porous scaffolds from mineralized collagen.
AB  - Porous 3D structures from mineralized collagen were fabricated applying a
      procedure in which collagen fibril reassembly and precipitation of
      nanocrystalline hydroxyapatite (HA) occur simultaneously. The resulting matrices
      were evaluated in vitro with respect to their suitability as scaffolds for bone
      tissue engineering. We found a high capacity of the material to bind serum
      proteins as well as to absorb Ca2+ ions, which could be advantageous to promote
      cell attachment, growth, and differentiation. Human bone marrow stromal cells
      (hBMSCs) were seeded onto the 3D scaffolds and cultivated for 4 weeks in the
      presence and absence of osteogenic supplements. We studied viability,
      proliferation, and osteogenic differentiation in terms of total lactate
      dehydrogenase (LDH) activity, DNA content, and alkaline phosphatase (ALP)
      activity. Furthermore, the expression for bone-related genes (ALP, bone sialo
      protein II (BSP II), and osteocalcin) was analyzed. In our investigation we found
      a 2.5-fold to 5-fold raise in DNA content and an increase of ALP activity for
      osteogenic induced hBMSC on collagen HA scaffolds. The expression of ALP and BSP
      II in these cells was also stimulated in the course of cultivation; however, we
      did not detect an upregulation of osteocalcin gene expression. These data
      suggest, that porous collagen HA scaffolds are suitable for the expansion and
      osteogenic differentiation of hBMSC and are therefore promising candidates for
      application as bone grafts.

PMID- 18615471
TI  - Inverted human umbilical arteries with tunable wall thicknesses for nerve
      regeneration.
AB  - Tubular nerve guides have shown a potential to bridge nerve defects, by directing
      neuronal elongation, localizing growth factors, and inhibiting fibrotic cellular
      ingrowth. These investigations describe a novel acellular scaffold derived from
      the human umbilical cord artery that aims to enhance nerve regeneration by
      presenting a unique mechanical and chemical environment to the damaged nerve
      ends. A rapid, semiautomated dissection technique is described that isolates the
      human umbilical artery (HUA) from the umbilical cord, after which the vessel is
      decellularized using sodium dodecyl sulfate (SDS). The artery is turned inside
      out to produce a 3D scaffold, that unlike previous vessels for nerve repair, is
      more resistant to collapse. The scaffold has the potential as either an acellular
      bridge-implant, or for in vitro nerve regeneration. Stress-strain relationships
      and suture retention were assessed to determine whether the material had similar
      mechanical properties to native nerves. A dual process-flow perfusion bioreactor
      was developed to assess glucose mass transfer, and to investigate the culture of
      neuronal-like PC12 cells within the scaffold. These investigations have shown the
      automated dissecting method yields a smooth tubular scaffold, where wall
      thickness can be tuned to alter the mechanical behavior of the scaffold.
      Inverting the scaffold prevents collapse, with the decellularized iHUA having
      comparable mechanical properties to native nerves. Bioreactor cultures with PC12
      cells seeded within iHUA lumenal void were shown to adhere and migrate into the
      preexisting ECM after 11 days of culture. These investigations show the potential
      of the iHUA as a unique 3D scaffold that may enhance nerve regeneration.

PMID- 18615472
TI  - A prospective consecutive study of instrumented posterolateral lumbar fusion
      using synthetic hydroxyapatite (Bongros-HA) as a bone graft extender.
AB  - A prospective, single institution, clinical case-matched, radiographic study was
      undertaken. Thirty-two patients underwent posterior lumbar interbody fusion with
      cages containing laminectomized bone chips and posterolateral lumbar fusion with
      pedicle screws. Autogenous bone graft (3 mL) plus 3 mL of hydroxyapatite was
      placed in one side of a posterolateral gutter, and 6 mL of autogenous iliac bone
      graft was placed on the other side. Bony union, volumes of fusion mass, and bone
      absorption rates were postoperatively evaluated using simple radiographs and 3D
      CT scans. Average postoperative Lenke scores at 3 and 6 months in the
      hydroxyapatite group were statistically higher than in the autograft group, but
      at 12 months no difference was found between the hydroxyapatite and autograft
      groups in terms of fusion rate. Complete fusion rates by 3D-CT were 86.7% in the
      hydroxyapatite group and 88.9% in the autograft group, which are not
      significantly different. Volumes of fusion mass and bone absorption rates at 12
      months were 2.35 mL in the hydroxyapatite group and 1.31 mL in the autograft
      group. The mean fusion mass volume was greater in the hydroxyapatite group than
      in the autograft group. Lumbar posterolateral fusion using a mixture of
      hydroxyapatite artificial bone and autogenous bone graft showed good bony union
      similar to that shown with autogenous bone only. This study suggests that
      hydroxyapatite bone chips could be used usefully as a bone-graft extender in
      short-segment posterolateral spinal fusion.

PMID- 18615473
TI  - Current developments and future prospects for heart valve replacement therapy.
AB  - Valve replacement is the most common surgical treatment in patients with advanced
      valvular heart disease. Mechanical and bio-prostheses have been the traditional
      heart valve replacements in these patients. However, currently the heart valves
      for replacement therapy are imperfect and subject patients to one or more ongoing
      risks, including thrombosis, limited durability, and need for re-operations due
      to the lack of growth in pediatric populations. Furthermore, they require an open
      heart surgery, which is risky for elderly and young children who are too weak or
      ill to undergo major surgery. This article reviews the current state of the art
      of heart valve replacements in light of their potential clinical applications. In
      recent years polymeric materials have been widely studied as potential prosthetic
      heart valve material being designed to overcome the clinical problems associated
      with both mechanical and bio-prosthetic valves. The review also addresses the
      advances in polymer materials, tissue engineering approaches, and the development
      of percutaneous valve replacement technology and discusses the future prospects
      in these fields.

PMID- 18615474
TI  - Recellularization of biological heart valves with human vascular cells: in vitro
      hemocompatibility assessment.
AB  - Coverage of cardiovascular bioprostheses with autologous endothelium is used for
      the purpose of improving blood compatibility. The aim of our study was to analyze
      endothelialization potential of glutaraldehyde-fixed heart valves, cellular
      functions of seeded endothelial cells (EC), and the impact of a two-stage seeding
      protocol using human vascular fibroblasts (FB) and EC from saphenous veins
      (HSVEC) on cellular functional properties in vitro. Adherence and morphology of
      adhered cells were assessed by scanning electronic microscopy and
      immunohistochemistry. Reproducible, complete surface coverage with EC was
      established on decellularized and glutaraldehyde-fixed bovine pericardium.
      Analyzing functional properties of cells directly adhered to biomaterial revealed
      nonproliferative cells, which were capable of inflammatory stimulation in terms
      of TNF-induced increase in interleukin-6 secretion and adhesion of inflammatory
      cells. Furthermore, EC showed sustained antithrombotic properties quantified by
      platelet adhesion onto EC and prostacyclin secretion by EC. Preseeding with
      vascular fibroblasts using a two-stage seeding protocol induced EC proliferation
      and improved inflammatory and anti-thrombotic functions. Cardiovascular
      biomaterials differ significantly in their potential to allow for adhesion of
      human EC. Successfully endothelialized biomaterial, however, revealed cellular
      properties which are likely to be favorable to improving performance of
      biomaterials. Two-stage seeding adds regenerative potential and improves cell
      functions of adherent EC.

PMID- 18615475
TI  - Structure and surface reactivity of novel nanoporous alumina fillers.
AB  - Recent studies have shown that the particle size of fillers used for the
      reinforcement of dental resin composites should be multimodally distributed, in
      which micron-sized fillers are mixed with nanoparticles so as to achieve a higher
      filler level in the resin, and should be kept well dispersed so as to be
      functionalized by a silane. In this study, porous alumina monoliths with high
      specific surface area, measured by the Brunauer-Emmett-Teller (BET) method, were
      obtained using a novel preparation method. Structure and surface reactivity have
      been investigated as functions of temperature and chemical treatments. The
      impregnation of the as-prepared material by trimethyletoxysilane (TMES)
      stabilized alumina with high specific surface area at higher temperature. FTIR
      study has described the effect of TMES treatment and temperature on the structure
      of the material. The use of allyldimethoxysilane (ADMS), as a probe molecule for
      measuring the surface reactivity, has allowed us to show that the treatment of
      samples with TMES and their reheating at 1300 degrees C results in adsorption
      sites which give stronger chemical bonds. This preliminary study has, therefore,
      allowed us to optimize the structural and surface treatment of experimental
      fillers before their use in the reinforcement of resin composites or resin
      modified glass ionomer cements.

PMID- 18615476
TI  - Novel de novo SHANK3 mutation in autistic patients.
AB  - A number of studies have confirmed that genetic factors play an important role in
      autism spectrum disorder (ASD). More recently de novo mutations in the SHANK3
      gene, a synaptic scaffolding protein, have been associated with the ASD
      phenotype. As part of our gene discovery strategy, we sequenced the SHANK3 gene
      in a cohort of 427 ASD subjects and 190 controls. Here, we report the
      identification of two putative causative mutations: one being a de novo deletion
      at an intronic donor splice site and one missense transmitted from an epileptic
      father. We were able to confirm the deleterious effect of the splice site
      deletion by RT-PCR using mRNA extracted from cultured lymphoblastoid cells. The
      missense mutation, a leucine to proline at amino acid position 68, is perfectly
      conserved across all species examined, and would be predicted to disrupt an alpha
      helical domain. These results further support the role of SHANK3 gene disruption
      in the etiology of ASD.

PMID- 18615477
TI  - Urea production capacity in the wood frog (Rana sylvatica) varies with season and
      experimentally induced hyperuremia.
AB  - Wood frogs (Rana sylvatica) can accumulate substantial amounts of urea during
      fall and winter. In this study, maximal urea production capacity was examined in
      R. sylvatica collected at various times of the year and in response to
      experimental hyperuremia and dehydration. Activity and expression of carbamoyl
      phosphate synthetase I (CPS I), the hepatic regulatory enzyme of the urea cycle,
      were used as indicators of urea production capacity. The high levels of CPS I
      activity in summer frogs were maintained through much of winter, a time when many
      metabolic processes are downregulated, suggesting that urea production is
      important during hibernation. In laboratory experiments, hyperuremia in fully
      hydrated frogs caused CPS I activity to decrease by approximately 41%, suggesting
      that urea functions as a feedback inhibitor. In contrast, CPS I activity was
      maintained in hyperuremic, dehydrated frogs. The significance of this response is
      unclear, although perhaps urea functions to counteract inhibitory effects of
      concentrated salts. Generally, changes in CPS I activity were not reflected by
      corresponding changes in CPS I quantity, indicating that this enzyme is not
      primarily regulated through transcription and translation; rather, control may be
      achieved by posttranslational modifications and/or feedback inhibition. Our
      findings suggest that maintenance of urea production capacity in hibernating R.
      sylvatica facilitates accumulation of this osmolyte, which has important roles in
      the winter biology of this species.

PMID- 18615478
TI  - DRD2 C32806T modifies the effect of child-rearing environment on adulthood
      novelty seeking.
AB  - Preliminary evidence suggests that there may be longitudinal interactions between
      environmental and genetic factors in predicting Novelty seeking. We have
      previously found in small and selected subsample from the Cardiovascular Risk in
      Young Finns study, that an association between the polymorphism of dopamine
      receptor D4 was moderated by the childhood environment, as indexed by hostile
      maternal child-rearing. We wanted to replicate this finding in a population based
      sample of 1,114 men and women using another candidate gene of dopaminergic
      system, that is, the dopamine receptor D2 (DRD2). The child-rearing environment
      of the participants was assessed by their mothers when the participants were
      children or adolescents, and adulthood Novelty seeking was self-rated by the
      participants 17 and 21 years later at the ages of 24-39. Genotyping of DRD2
      C32806T (rs 1800497) was performed using TaqMan 5'nuclease assay. DRD2 was not
      directly associated with Novelty seeking, but there was a significant DRD2 x
      strict maternal disciplinary style interaction in predicting Novelty seeking (F =
      7.08, P = 0.008). The interaction showed that when the child-rearing environment
      was punitive, participants carrying any A1 allele of the DRD2 gene had higher
      scores on Novelty seeking than carriers of the A2/A2 genotype. The genotype had
      no effect on Novelty seeking when the childhood environment was more favorable.
      The findings suggest that the DRD2 may have an environmentally moderated impact
      on Novelty seeking and that the origins of such an association may lie already in
      childhood.

PMID- 18615479
TI  - COMT val158met modulates association between brain white matter architecture and
      IQ.
AB  - The intelligence quotient (IQ) is typically associated with the architecture of
      gray and white matter in specific brain regions, and this association appears to
      be genetically based. However, specific sources of genetic variation for the
      association have not been studied extensively. Using diffusion tensor imaging in
      15 mental retardation patients and 80 healthy volunteers, we studied the
      association between white matter architecture and IQ and also investigated the
      effects of COMT val158met on this association. The results showed that fractional
      anisotropy (FA) values in the prefrontal lobe and the hippocampus formation were
      associated with IQ and that val158met may affect this association. Subjects who
      were val homozygous showed steeper slopes for regression of the FA value on IQ
      than met carriers. Our findings suggest that COMT val158met may contribute to
      intelligence by affecting the association between IQ and the white matter
      architecture in the prefrontal lobe and the hippocampal formation.

PMID- 18615480
TI  - Association of ERCC1 polymorphisms and susceptibility to nasopharyngeal
      carcinoma.
AB  - The normal function of excision repair cross complementing group 1 (ERCC1) is
      essential for maintaining genomic integrity and preventing cellular neoplastic
      transformation, and multiple studies have reported an association between ERCC1
      polymorphisms and increased risk of cancers. To test whether the genetic variants
      of ERCC1 gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the
      8092 C > A and 19007 C > T single nucleotide polymorphisms (SNPs) and the
      haplotypes of ERCC1 between 267 patients with NPC and 304 healthy controls.
      Linkage disequilibrium was observed between the two SNPs loci (D' = 0.861).
      Significant differences of allele frequencies were found for ERCC1 8092C > A
      between the cases and controls. Individuals with 8092 C allele showed 1.411-fold
      (OR = 1.411, 95% CI, 1.076-1.850, P = 0.014) increased risk of developing NPC,
      and the CC haplotype was associated with a significantly increased risk of NPC
      (OR = 1.712; 95% CI, 1.211-2.421; P = 0.013). No interactions were found between
      8092C > A polymorphism and genders, smoking status and alcohol consumption. These
      results suggested that the polymorphism of ERCC1 8092 C > A might be a
      contributing factor in the development of NPC in Chinese population.

PMID- 18615481
TI  - The impact of T and N stage on long-term survival of rectal cancer patients in
      the community.
AB  - BACKGROUND AND OBJECTIVES: Use of the TNM staging system has been encouraged for
      rectal cancer patients. This study examined the impact of T and N stages on long
      term survival as well as the performance of associated risk classification
      systems. METHODS: Patients who underwent surgery for rectal adenocarcinoma from
      1988 to 2004 were identified in the Surveillance, Epidemiology, and End Results
      (SEER) database. Kaplan-Meier survival analysis was performed for subgroups of
      patients defined by T and N stage. RESULTS: For the overall population of 30,826
      patients, both T and N stage significantly impacted overall survival (P < 0.001).
      N stage variably affected survival for subgroups of patients based on T stage,
      whereas T stage significantly affected survival regardless of N stage. A
      previously developed risk classification system that assigns one of four risk
      levels outperformed AJCC group staging in this cohort. Based on long-term
      outcomes, a modified risk classification system was constructed which was highly
      prognostic for long-term overall survival (P < 0.001). CONCLUSIONS: Rectal cancer
      patients experience widely varying survival rates based on extent of disease. A
      new risk classification system is proposed that provides better prognostic
      information than AJCC group staging, suggesting current rectal cancer staging
      systems may be improved with appropriate revisions.

PMID- 18615483
TI  - T40214/PEI complex: a potent therapeutics for prostate cancer that targets STAT3
      signaling.
AB  - BACKGROUND: Prostate cancer (PC) is the most common cancer among men in American
      and the second leading cause of cancer death. The treatment options employed for
      patients with advanced and metastatic PC are limited. As a critical mediator of
      oncogenic signaling, STAT3 is active in 82% of patients with PC. STAT3 has become
      a very important molecular target for PC therapy since it upregulates the
      oncogenes encoding apoptosis inhibitors, cell cycle regulators, and inducers of
      angiogenesis. However, no anti-tumor drug whose primary mode of action is to
      target STAT3 has yet reached the clinic. To this end, we have laid the initial
      groundwork to develop the STAT3-inhibiting G-quartet oligodeoxynucleotide (GQ
      ODN), T40214, for treatment of PCs. METHODS: We employed in vitro and in vivo
      assays, including Western blots, EMSA, cell cycle analysis, TUNEL and xenograft
      models, to determine the drug efficacy and mechanism of T40214/PEI complex.
      RESULTS: The results demonstrated that (i) T40214 significantly inhibited STAT3
      activation and induced apoptosis in both androgen-dependent and androgen
      independent PC cells; (ii) T40214 delivered by ployethylenimine (PEI)
      significantly suppressed prostate tumor growth in tumor-bearing nude mice due to
      that T40214 inhibited STAT3 activation and then greatly promoted apoptosis,
      reduced angiogenesis and cell proliferation in prostate tumors. CONCLUSION: Our
      studies suggested that STAT3 is a critical oncogenic signal, which strongly
      influences the progression of PCs and that T40214/PEI complex is a promising
      candidate for treatment of patients with prostate tumors and represents a novel
      strategy for PC therapy.

PMID- 18615484
TI  - Failure to confirm the association between the PIK4CA gene and schizophrenia in a
      Japanese population.

PMID- 18615482
TI  - Depletion of intracellular zinc increases expression of tumorigenic cytokines
      VEGF, IL-6 and IL-8 in prostate cancer cells via NF-kappaB-dependent pathway.
AB  - BACKGROUND: Zinc accumulation diminishes early in the course of prostate
      malignancy and continues to decline during progression toward hormone-independent
      growth. In contrast, constitutive levels of NF-kappaB activity increase during
      progression of prostate cells toward greater tumorigenic potential. We have
      reported previously that physiological levels of zinc suppress NF-kappaB activity
      in prostate cancer cells and reduce expression of pro-angiogenic and pro
      metastatic cytokines VEGF, IL-6, IL-8, and MMP-9 associated with negative
      prognostic features in prostate cancer. METHODS: Intracellular zinc levels were
      examined by atomic absorption spectroscopy. NF-kappaB activity was examined by
      TransAm and Luciferase reporter assays, and Western blot analysis of p50 nuclear
      translocation. VEGF, IL-6 and IL-8 levels were assessed by ELISA. RESULTS:
      Selective zinc deficiency induced by the membrane-permeable zinc chelator
      N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN) increases activation
      of NF-kappaB and up-regulates expression of the NF-kappaB controlled pro
      angiogenic and pro-metastatic cytokines VEGF, IL-6 and IL-8 in androgen
      independent PC-3 and DU-145 prostate cancer cells. Pre-incubation with I kappaB
      alpha dominant mutant adenovirus efficiently blocks expression of these cytokines
      in zinc deficient cells indicating that the observed effects are NF-kappaB
      dependent. CONCLUSIONS: Our findings suggest that zinc deficiency may contribute
      to the tumor progression via augmented expression of the NF-kappaB-dependent pro
      tumorigenic cytokines.

PMID- 18615485
TI  - Taste difference thresholds for monosodium glutamate and sodium chloride in
      pigtail macaques (Macaca nemestrina) and spider monkeys (Ateles geoffroyi).
AB  - The purpose of this study was to determine taste difference thresholds for
      monosodium glutamate (MSG) and sodium chloride (NaCl) in pigtail macaques (Macaca
      nemestrina) and spider monkeys (Ateles geoffroyi). Using a two-bottle preference
      test of brief duration, three animals of each species were presented with four
      different reference concentrations of 50, 100, 200, and 400 mM of a tastant and
      tested for their ability to discriminate these from lower concentrations of the
      same tastant. The just noticeable differences (JNDs), expressed as Weber ratios
      (DeltaI/I), were found to range from 0.1 to 0.5 for MSG and 0.2 to 0.45 for NaCl
      in the pigtail macaques, with a significant tendency for higher Weber ratios with
      higher reference concentrations. In the spider monkeys, JNDs ranged from 0.15 to
      0.4 for MSG and 0.1 to 0.25 for NaCl, with Weber ratios staying fairly constant
      across the reference concentrations tested. Thus, the JNDs were found to be
      generally similar in both species and to be at least as low as those found in
      humans for MSG and NaCl, as well as those found in spider monkeys for sucrose.
      The results support the assumption that both pigtail macaques and spider monkeys
      may use differences in perceived intensity of MSG and NaCl as a criterion for
      food selection.

PMID- 18615486
TI  - Androgen regulation of multidrug resistance-associated protein 4 (MRP4/ABCC4) in
      prostate cancer.
AB  - BACKGROUND: MRP4/ABCC4 is an ATP-binding cassette transporter expressed in normal
      prostate. This study aimed to define the pattern of MRP4/ABCC4 expression in
      normal and malignant prostate tissue and the relationship of MRP4/ABCC4
      expression and function in response to androgen signaling. METHODS: Eighty-four
      radical prostatectomy specimens from patients with localized prostate cancer (PC)
      (22 neoadjuvant androgen ablation, AA, 62 no AA), 42 non-cancer and 16 advanced
      PCs were assessed for MRP4/ABCC4 mRNA/protein expression. The effect of DHT and
      bicalutamide on LNCaP cells was assessed by immunoblotting. HEK293 cells (+/
      MRP4/ABCC4) were assessed for the ability to efflux androgens and anti-androgens.
      RESULTS: MRP4/ABCC4 mRNA/protein levels were higher in localized PC compared to
      non-cancer (P = 0.006). MRP4/ABCC4 levels were significantly decreased in PCs
      treated with AA compared to cancers exposed to normal testosterone levels (P <
      0.0001). MRP4/ABCC4 expression in normal human tissues was limited to the
      prostate and the renal tubules. MRP4/ABCC4 protein levels increased in LNCaP
      cells after DHT which was partially blocked by bicalutamide. However, DHT did not
      alter the activation of the MRP4/ABCC4 promotor in luciferase reporter assays and
      testosterone, DHT, flutamide and hydroxy-flutamide were not substrates for
      MRP4/ABCC4. DISCUSSION: Elevated MRP4/ABCC4 expression is found in malignant
      compared to benign prostate tissue while lower MRP4/ABCC4 expression is seen
      after AA. Furthermore, MRP4/ABCC4 is upregulated by androgen and downregulated by
      anti-androgen treatment in vitro potentially through an indirect mode of action.
      These data strongly suggest that MRP4/ABCC4 is an androgen-regulated gene
      important in the progression to PC and may be a potential drug target.

PMID- 18615487
TI  - Influence of different air-abrasive powders on cell viability at biologically
      contaminated titanium dental implants surfaces.
AB  - Studies have indicated that oral biofilm formation at structured titanium
      surfaces interferes with cell adhesion and proliferation, and its removal by
      means of conventional treatment procedures may not be sufficient to render these
      surfaces biologically acceptable. Therefore, the aim of the study was to evaluate
      the influence of different air-abrasive powders on cell viability at biologically
      contaminated titanium dental implant surfaces. Intraoral splints were used to
      collect an in vivo biofilm on sandblasted and acid-etched titanium discs for 48
      h. A single (1x) and repeated (2x) use of four different powders (amino acid
      glycine or sodium bicarbonate particles; range of mean particle size (d(v50)):20
      75 microm) was applied at two distances (1 and 2 mm) and angles (30 degrees and
      90 degrees) to the surfaces. Specimens (2x) were incubated with SaOs-2 cells for
      7 days. Residual biofilm (RB) areas (%), and surface alterations (SEM) (1x and
      2x), as well as SaOs-2 cell viability, expressed as mitochondrial cell activity
      (MA) (counts/second) (2x specimens), were assessed. Comparable mean RB areas were
      observed within and between groups after both 1x (RB: 0.0% +/- 0.0% to 5.7% +/-
      5.7%) and 2x (RB: 0.0% +/- 0.0%) treatments. All surface treatments did not lead
      to MA (2x) values comparable to the sterile control group. However, sodium
      bicarbonate particles resulted in significantly higher MA (2x) values than amino
      acid glycine powders of different sizes. This was associated with pronounced
      alterations of the surface morphology (2x). Within the limits of the present
      study, it was concluded that SaOs-2 cell viability at biologically contaminated
      titanium surfaces was mainly influenced by the particle type of the powder.

PMID- 18615488
TI  - Surface topography of zirconia implants does not alter action potentials of
      isolated rat sciatic nerves.
AB  - The purpose of this study was to explore the effects of airborne-particle
      abrasion and selective infiltration etching of a yttrium-partially stabilized
      tetragonal zirconia polycrystal (Y-TZP) implant surfaces on nerve conduction.
      Particle-abraded Y-TZP (P/Y-TZP), selective infiltration etched Y-TZP (SIE/Y
      TZP), and commercially pure titanium (CP-Ti) were used in the study (n = 5).The
      compound action potentials of the right and left sciatic nerves of eight
      sacrificed rats were quantified at the in vitro level. The implants were brought
      into intimate contact with the nerves and the time required for initiation of
      compound action potentials (TcAP), depolarization (Dp), repolarization (Rp), and
      amplitude of evoked compound action potentials (cAPs) were recorded before and
      after contact with the implants. The difference in cAPs between the basal
      response and after contact with CP-Ti implant was significant (p < 0.05). Time
      dependent changes in cAPs of P/Y-TZP and SIE/Y-TZP groups and their basal nerve
      responses were similar (p > 0.05). Within- and between-subject comparisons
      revealed that TcAP, Dp, and Rp values for all groups were similar (p > 0.05).
      Particle-abraded and selective infiltration-etched zirconia implant surfaces do
      not alter nerve conduction beyond physiologic limits.

PMID- 18615489
TI  - Comparative study of the in vitro interaction of two fibroblast cell lines with a
      polyalkyl-imide hydrogel.
AB  - The in vitro effects of polyalkyl-imide hydrogel (PAI) containing 96% pyrogen
      free water on the viability, apoptosis, cell shape and metabolic activities of
      murine 3T3 and human Detroit 555 fibroblasts were investigated. Analysis of the
      viscous-elastic properties and the ultrastructure of PAI, performed by rheometer
      and AFM respectively, showed that the material has the typical characteristics of
      hydrogel, including a three-dimensional configuration of molecules arranged in a
      regular network with many discrete caveolae where most of the water is captured.
      Hydrogel biocompatibility was found to be high for both cell lines, with some
      differences. Cell viability decreased more in 3T3 cells than Detroit 550
      fibroblasts when cultured in the presence of 100 mg/ml hydrogel but not at
      concentrations of 25 and 50 mg/ml hydrogel. The period of incubation with PAI (24
      and 48 h) only partially affected cell viability. Apoptosis, most likely due to
      cells' inability to adhere to the polymer, was the only type of cell death
      observed. Fibroblasts grown in the presence of polymer were always metabolically
      active since they continued to synthesize collagen. In conclusion, PAI hydrogel,
      even at high concentrations, was biocompatible for both fibroblasts, but in
      particular for human cells, thus encouraging its use as a dermal filler.

PMID- 18615490
TI  - Image signal-to-noise ratio estimation using Shape-Preserving Piecewise Cubic
      Hermite Autoregressive Moving Average model.
AB  - We propose to cascade the Shape-Preserving Piecewise Cubic Hermite model with the
      Autoregressive Moving Average (ARMA) interpolator; we call this technique the
      Shape-Preserving Piecewise Cubic Hermite Autoregressive Moving Average
      (SP2CHARMA) model. In a few test cases involving different images, this model is
      found to deliver an optimum solution for signal to noise ratio (SNR) estimation
      problems under different noise environments. The performance of the proposed
      estimator is compared with two existing methods: the autoregressive-based and
      autoregressive moving average estimators. Being more robust with noise, the
      SP2CHARMA estimator has efficiency that is significantly greater than those of
      the two methods.

PMID- 18615491
TI  - Measuring satisfaction with nursing care among hospitalized patients: refinement
      of a Spanish version.
AB  - This study was designed to improve the psychometrics of English and Spanish
      measures of hospitalized patients' satisfaction with nursing care. One hundred
      Spanish-speaking participants in the northeastern and southwestern United States
      completed a new 20-item Spanish version; 64 of the same participants also
      completed the English version. Correlations between item pairs (p < .001, r = .56
      .96) and total scores of both versions (r = .92, p < .01), and similar factor
      structures support equivalence of the two versions. Evidence for construct
      validity is also presented. Results surpass standards for new instruments and
      support the utility of this much needed, bilingual measure of inpatient
      satisfaction with nursing care.

PMID- 18615492
TI  - Bombesin-modified 6-14 C-terminal fragments adsorption on silver surfaces:
      influence of a surface substrate.
AB  - Surface-enhanced Raman scattering (SERS) spectroscopy has been applied to
      investigate the interaction with a silver colloidal surface of following seven 6
      14 fragments of bombesin (BN) C-terminus: cyclo[D-Phe(6),His(7),Leu(14)]BN(6-14),
      [D-Phe(6),Leu-NHEt(13),des-Met(14)]BN(6-14), [D-Phe(6),Leu(13)-(R)-p-chloro
      Phe(14)]BN(6-14), [D-Phe(6),beta-Ala(11),Phe(13),Nle(14)]BN(6-14), [D-Tyr(6),beta
      Ala(11),Phe(13),Nle(14)]BN(6-14), [D-Tyr(6),beta-Phe(11),Phe(13),Nle(14)OH]BN(6
      14), and [D-Cys(6),Asn(7),D-Ala(11),Cys(14)]BN(6-14), potent r-GRP-R receptor
      antagonists used in chemotherapy and potential effective drugs in cancer
      treatment. The adsorption active sites and molecular orientations on the
      colloidal silver surface have been determined on the basis of SERS "surface
      selection rules" subsequent to a detailed SERS analysis. In addition, the
      similarities and differences of these spectra with the SERS spectra of the
      peptides immobilized on a roughened silver electrode surface have been examined.
      From the data, suggestion has been made about structural properties of these
      peptides on the colloidal surface.

PMID- 18615493
TI  - Inactivation of N-TIMP-1 by N-terminal acetylation when expressed in bacteria.
AB  - The high-affinity binding of tissue inhibitors of metalloproteinases (TIMPs) to
      matrix metalloproteinases (MMPs) is essential for regulation of the turnover of
      the extracellular matrix during development, wound healing, and progression of
      inflammatory diseases, such as cancer, atherosclerosis, and arthritis.
      Bacterially expressed N-terminal inhibitory domains of TIMPs (N-TIMPs) have been
      used extensively for biochemical and biophysical study of interactions with MMPs.
      Titration of N-TIMP-1 expressed in E. coli indicates, however, that only about
      42% of the protein is active as an MMP inhibitor. The separation of inactive from
      fully active N-TIMP-1 has been achieved both by MMP affinity and by high
      resolution cation exchange chromatography at an appropriate pH, based on a slight
      difference of charge. Purification by cation exchange chromatography with a Mono
      S column enriches the active portion of N-TIMP-1 to >95%, with K(i) of 1.5 nM for
      MMP-12. Mass spectra reveal that the inactive form differs from active N-TIMP-1
      in being N-terminally acetylated, underscoring the importance of the free alpha
      NH(2) of Cys1 for MMP inhibition. N(alpha)-acetylation of the CTCVPP sequence
      broadens the N-terminal sequence motifs reported to be susceptible to alpha-amino
      acetylation by E. coli N-acetyl transferases.

PMID- 18615494
TI  - STa peptide analogs for probing guanylyl cyclase C.
AB  - Guanylyl cyclase C (GC-C), universally overexpressed on primary and metastatic
      colorectal carcinoma cells, is activated by endogenous ligands, guanylin, and
      uroguanylin, and by exogenous 18-residue heat-stable enterotoxins (STa) produced
      by diarrheagenic bacteria. Two 12-residue STa analogs with alternate combinations
      of two interlocked disulfide bonds, peptides 3 and 6, were synthesized by
      orthogonal solid phase synthesis routes. Peptides 3 and 6 bound GC-C with a rank
      order potency of STa > peptide 3 > peptide 6. Peptides 3 and 6 behaved as
      agonists in stimulating cGMP production. The results reveal that the toxic domain
      of STa can be reduced to 12 amino acids.

PMID- 18615495
TI  - In vivo and in vitro characterization of CCK8 bearing a histidine-based chelator
      labeled with 99mTc-tricarbonyl.
AB  - The development of receptor targeting radiolabeled ligands has gained much
      interest in recent years for diagnostic and therapeutic applications in nuclear
      medicine. Cholecystokinin (CCK) receptors have been shown to be overexpressed in
      a subset of neuroendocrine and other tumors. We are evaluating binding and
      biodistribution properties of a CCK8 peptide derivative labeled with (99m)Tc(I)
      tricarbonyl. The CCK8 peptide was modified at its N-terminus by adding to its N
      terminus two lysine-histidine modules (KH), where histidine is coupled to the
      side chain of the lysine ((KH)(2)-CCK8). (99m)Tc(I)-tricarbonyl was generated
      with the IsoLinktrade mark kit. A431 cells stably transfected with a cDNA
      encoding for the human CCK2 receptor were utilized to determine binding affinity,
      internalization, and retention of the labeled peptide, in comparison with wild
      type A431 cells. A nude mouse tumor model was obtained by generating A431-CCK2R
      and A431-control tumors in opposite flanks of the animals. High specific activity
      labeling with (99m)Tc was achieved. In A431-CCK2R cells, specific saturable
      binding was observed as well as evident internalization of the radiolabeled
      peptide after binding. Biodistribution experiments showed rapid, specific
      localization of (KH)(2)-CCK8 on A431-CCK2R xenografts compared with control
      tumors, although absolute uptake values were not markedly higher compared with
      background activity. Clearance of unbound radioactivity was both urinary and
      hepatobiliary. In imaging experiments, while targeting to CCK2R positive tumors
      could be appreciated, there was poor contrast between target and nontarget areas.
      (KH)(2)-CCK8 shows adequate in vitro and in vivo properties for CCK2R targeting
      although improvement of biodistribution warrant further development.

PMID- 18615496
TI  - Confocal Raman microscopy on single living young and old erythrocytes.
AB  - Raman confocal microscopy, including the techniques of point Raman spectra, line
      mapping, 2D mapping, and time-dependent spectrum monitoring performed with 514.5
      nm excitation light, was used in a comparative study on the distribution and
      oxidation states of hemoglobin (Hb) in young and old mature erythrocytes. It is
      demonstrated that in contrast to the homogeneous distribution of the Hb in young
      cells, there are more Hb distribution around the cell membrane in old
      erythrocyte. The proteins exhibit some extent of aggregation and conformational
      change, present less ability of oxidation, and lower oxygenation speed than the
      Hb in young erythrocytes. Our results also provide the first direct evidence of
      some intermediate oxygenated states of Hb between the two fully oxygenated (R)
      and deoxygenated (T) states in living erythrocyte, and give detail information
      about the conformational change of the intracellular Hb with time during the
      reoxygenation process.

PMID- 18615497
TI  - A pilot randomised controlled trial of a brief cognitive behavioural group
      intervention to reduce recurrence rates in late life depression.
AB  - OBJECTIVES: To standardise the delivery of a brief group cognitive behaviour
      therapy intervention (CBT-G). To apply the intervention in a research setting and
      to estimate its effect on recurrence rates in recently depressed older adults, in
      preparation for a definitive study. METHOD: A CBT-G therapy manual was produced
      and the Cognitive Therapy Rating Scale (CTS-R) modified to assess therapy
      delivery. Forty-five adults aged 60 and over who had met ICD-10 criteria for
      major depression in the previous year and were still taking antidepressant
      medication were randomly allocated to CBT-G/antidepressant combination or
      antidepressant alone. Depression severity was measured at baseline, randomisation
      and 6 and 12 months after start of CBT-G using the Montgomery Asberg Rating Scale
      for Depression (MADRS). RESULTS AND CONCLUSION: One-year recurrence rates on the
      MADRS were encouragingly lower in participants receiving CBT-G [5/18 (27.8%)]
      compared with controls [8/18 (44.4%)] although this did not achieve statistical
      significance (adjusted RR 0.70 [95% CI 0.26-1.94]). In contrast, overall scores
      on the secondary outcome measure, the Beck Depression Inventory, increased in
      participants receiving CBT-G. The CBT-G manual was successfully implemented and
      therapy delivery achieved an overall satisfactory level of competence. We believe
      that evaluation of this promising intervention in a full-scale trial is
      warranted.

PMID- 18615498
TI  - Participation of mu-opioid, GABA(B), and NK1 receptors of major pain control
      medullary areas in pathways targeting the rat spinal cord: implications for
      descending modulation of nociceptive transmission.
AB  - Several brain areas modulate pain transmission through direct projections to the
      spinal cord. The descending modulation is exerted by neurotransmitters acting
      both at spinally projecting neurons and at interneurons that target the
      projection neurons. We analyzed the expression of mu-opioid (MOR), gamma
      aminobutyric acid GABA(B), and NK1 receptors in spinally projecting neurons of
      major medullary pain control areas of the rat: rostroventromedial medulla (RVM),
      dorsal reticular nucleus (DRt), nucleus of the solitary tract, ventral reticular
      nucleus, and lateralmost part of the caudal ventrolateral medulla. The retrograde
      tracer cholera toxin subunit B (CTb) was injected into the spinal dorsal horn,
      and medullary sections were processed by double immunocytochemistry for CTb and
      each receptor. The RVM contained the majority of double-labeled neurons followed
      by the DRt. In general, high percentages of MOR- and NK1-expressing neurons were
      retrogradely labeled, whereas GABA(B) receptors were mainly expressed in neurons
      that were not labeled from the cord. The results suggest that MOR and NK1
      receptors play an important role in direct and indirect control of descending
      modulation. The co-localization of MOR and GABA(B) in DRt neurons also
      demonstrated by the present study suggests that the pronociceptive effects of
      this nucleus may be controlled by local opoidergic and GABAergic inhibition of
      the pronociception increased during chronic pain.

PMID- 18615499
TI  - Scientific method, abduction, and clinical reasoning.
AB  - This special issue of the Journal of Clinical Psychology comprises six
      theoretical papers that are concerned with the interconnected topics of
      scientific method, abductive inference, and clinical reasoning. The first four
      papers deal with the nature and limitations of a broad abductive theory of
      scientific method, and its application to clinical reasoning and case
      formulation. These are followed by three papers which in turn consider the
      prospects of using explanatory criteria to appraise competing models of
      psychopathy, examine the merits of a number of different psychometric
      perspectives on the assessment of psychopathology, and reject a core supposition
      of the orthodox approach to hypothesis testing.

PMID- 18615500
TI  - Requirement of the cyclic adenosine monophosphate response element-binding
      protein for hepatitis B virus replication.
AB  - The cyclic adenosine monophosphate-response element (CRE)-transcription factor
      complex participates in the regulation of viral gene expression and pathologic
      processes caused by various viruses. The hepatitis B virus (HBV) enhancer I
      directs liver-specific transcription of viral genes and contains a CRE sequence
      (HBV-CRE); however, whether the HBV-CRE and CRE-binding protein (CREB) are
      required for the HBV life cycle remains to be determined. This study was designed
      to investigate the role of CREB in HBV replication and gene expression. Sequence
      comparison analysis of 984 HBVs reported worldwide showed that the HBV-CRE
      sequence is highly conserved, indicating the possibility that it plays an
      important role in the HBV life cycle. The binding of CREB to the HBV-CRE site was
      markedly inhibited by oligonucleotides containing HBV-CRE and consensus CRE
      sequences in vitro and in vivo. The HBV promoter activity was demonstrated to be
      dependent upon the transactivation activity of CREB. Treatment with CRE decoy
      oligonucleotides reduced HBV promoter activity, and this was reversed by CREB
      overexpression. The levels of viral transcripts, DNA, and antigens were
      remarkably decreased in response to the overexpression of CREB mutants or
      treatment with the CRE decoy oligonucleotides, whereas enhancing CREB activity
      increased the levels of viral transcripts. In addition, introduction of a three
      base mutation into the HBV-CRE led to a marked reduction in HBV messenger RNA
      synthesis. CONCLUSION: Taken together, our results demonstrate that both
      replication and gene expression of HBV require a functional CREB and HBV-CRE. We
      have also demonstrated that CRE decoy oligonucleotides and the overexpression of
      CREB mutants can effectively block the HBV life cycle, suggesting that
      interventions against CREB activity could provide a new avenue to treat HBV
      infection.

PMID- 18615502
TI  - Temporal squama shape in fossil hominins: relationships to cranial shape and a
      determination of character polarity.
AB  - In 1943, Weidenreich described the squamosal suture of Homo erectus as long, low,
      and simian in character and suggested that this morphology was dependent upon the
      correlation between the size of the calvarium and the face. Many researchers now
      consider this character to be diagnostic of H. erectus. The relationship between
      cranial size and shape and temporal squama morphology, however, is unclear, and
      several authors have called for detailed measurements of squamosal variation to
      be collected before any conclusions are drawn regarding the nature of the
      morphology observed in H. erectus. Thirteen fossil and extant taxa were examined
      to address two questions: 1) Are size and shape of the temporal squama correlated
      with cranial vault morphology? and 2) Is the H. erectus condition plesiomorphic?
      To answer these questions, measurements were collected and indices were
      calculated for squamosal suture height, length, and area in relation to metric
      variables describing cranial size and shape. A two-dimensional morphometric study
      was also completed using High Resolution-Polynomial Curve Fitting (HR-PCF) to
      investigate correlations between curvature of the squamosal suture and curvature
      of the cranial vault. Results of both analyses indicate that squamosal suture
      form is related to cranial size and shape. Furthermore, the plesiomorphic
      condition of the squamosal suture for hominins was identified as high and
      moderately arched; this condition is retained in H. erectus and is distinct from
      the great ape condition. It is suggested that this similarity is the result of
      increased cranial length without a corresponding increase in cranial height.

PMID- 18615501
TI  - Ultrastructural examination of diffuse and specific tectopulvinar projections in
      the tree shrew.
AB  - Two pathways from the superior colliculus (SC) to the tree shrew pulvinar nucleus
      have been described, one in which the axons terminate in dense (or specific)
      patches and one in which the axon arbors are more diffusely organized (Luppino et
      al. [1988] J. Comp. Neurol. 273:67-86). As predicted by Lyon et al. ([2003] J.
      Comp. Neurol. 467:593-606), we found that anterograde labeling of the diffuse
      tectopulvinar pathway terminated in the acetylcholinesterase (AChE)-rich dorsal
      pulvinar (Pd), whereas the specific pathway terminated in the AChE-poor central
      pulvinar (Pc). Injections of retrograde tracers in Pd labeled non-gamma
      aminobutyric acid (GABA)-ergic wide-field vertical cells located in the lower
      stratum griseum superficiale and stratum opticum of the medial SC, whereas
      injections in Pc labeled similar cells in more lateral regions. At the
      ultrastructural level, we found that tectopulvinar terminals in both Pd and Pc
      contact primarily non-GABAergic dendrites. When present, however, synaptic
      contacts on GABAergic profiles were observed more frequently in Pc (31% of all
      contacts) compared with Pd (16%). Terminals stained for the type 2 vesicular
      glutamate transporter, a potential marker of tectopulvinar terminals, also
      contacted more GABAergic profiles in Pc (19%) compared with Pd (4%). These
      results provide strong evidence for the division of the tree shrew pulvinar into
      two distinct tectorecipient zones. The potential functions of these pathways are
      discussed.

PMID- 18615503
TI  - Basics in paleodemography: a comparison of age indicators applied to the early
      medieval skeletal sample of Lauchheim.
AB  - Recent advances in the methods of skeletal age estimation have rekindled interest
      in their applicability to paleodemography. The current study contributes to the
      discussion by applying several long established as well as recently developed or
      refined aging methods to a subsample of 121 adult skeletons from the early
      medieval cemetery of Lauchheim. The skeletal remains were analyzed by 13
      independent observers using a variety of aging techniques (complex method and
      other multimethod approaches, Transition Analysis, cranial suture closure,
      auricular surface method, osteon density method, tooth root translucency
      measurement, and tooth cementum annulation counting). The age ranges and mean age
      estimations were compared and results indicate that all methods showed smaller
      age ranges for the younger individuals, but broader age ranges for the older age
      groups.

PMID- 18615504
TI  - Genetic history of Southeast Asian populations as revealed by ancient and modern
      human mitochondrial DNA analysis.
AB  - The 360 base-pair fragment in HVS-1 of the mitochondrial genome were determined
      from ancient human remains excavated at Noen U-loke and Ban Lum-Khao, two Bronze
      and Iron Age archaeological sites in Northeastern Thailand, radio-carbon dated to
      circa 3,500-1,500 years BP and 3,200-2,400 years BP, respectively. These two
      neighboring populations were parts of early agricultural communities prevailing
      in northeastern Thailand from the fourth millennium BP onwards. The nucleotide
      sequences of these ancient samples were compared with the sequences of modern
      samples from various ethnic populations of East and Southeast Asia, encompassing
      four major linguistic affiliations (Altaic, Sino-Tibetan, Tai-Kadai, and
      Austroasiatic), to investigate the genetic relationships and history among them.
      The two ancient samples were most closely related to each other, and next most
      closely related to the Chao-Bon, an Austroasiatic-speaking group living near the
      archaeological sites, suggesting that the genetic continuum may have persisted
      since prehistoric times in situ among the native, perhaps Austroasiatic-speaking
      population. Tai-Kadai groups formed close affinities among themselves, with a
      tendency to be more closely related to other Southeast Asian populations than to
      populations from further north. The Tai-Kadai groups were relatively distant from
      all groups that have presumably been in Southeast Asia for longer-that is, the
      two ancient groups and the Austroasiatic-speaking groups, with the exception of
      the Khmer group. This finding is compatible with the known history of the Thais:
      their late arrival in Southeast Asia from southern China after the 10th-11th
      century AD, followed by a period of subjugation under the Khmers.

PMID- 18615505
TI  - The influence of serial prostate-specific antigen (PSA) screening on the PSA
      velocity at diagnosis.
AB  - BACKGROUND: A prostate-specific antigen (PSA) velocity (PSAV) >2 ng/mL during the
      year before diagnosis has been associated with an increased risk of prostate
      cancer-specific mortality (PCSM) after radical prostatectomy (RP) or radiation
      therapy. The objective of the current study was to examine whether the proportion
      of men with a PSAV >2 ng/mL per year has changed significantly during the PSA
      era. METHODS: The authors evaluated 1095 men from a prospective prostate cancer
      screening study who underwent RP between 1989 and 2002. For the purposes of this
      analysis, clinicopathologic features were compared between men who were treated
      during the following 3 periods: before 1995, from 1995 to 1998, and after 1998.
      Logistic regression analysis was used to evaluate for an association between the
      year of diagnosis and the proportion of men with a PSAV >2 ng/mL per year.
      RESULTS: Two hundred sixty-two of 1095 men (24%) had a PSAV >2 ng/mL per year.
      There was a statistically significant reduction in the proportion of men
      presenting with a PSAV >2 ng/mL per year over the study period. Specifically, 35%
      of men presented with a PSAV >2 ng/mL per year in the early period compared with
      only 22% and 12% in the middle and late periods, respectively (P < .001). Over
      the studied periods, there also was a significantly greater proportion of men
      with >2 PSA values obtained before diagnosis (P < .001). CONCLUSIONS: Men who
      were screened serially with PSA were less likely to present with a PSAV >2 ng/mL
      per year. This association lends support to the hypothesis that serial PSA-based
      screening may lead to a decrease in PCSM.

PMID- 18615506
TI  - Incidence trends of mantle cell lymphoma in the United States between 1992 and
      2004.
AB  - BACKGROUND: Mantle cell lymphoma (MCL) is a distinct subtype of B-cell non
      Hodgkin's lymphoma. To the authors' knowledge, little is known regarding its
      incidence patterns and associated factors. The purpose of the current study was
      to examine the incidence of MCL over a period of 13 years and to identify the
      factors associated with the incidence patterns. METHODS: Patients diagnosed with
      MCL between 1992 and 2004 were identified from the Surveillance, Epidemiology,
      and End Results (SEER) Tumor registries. SEER*Stat statistical software was used
      for analysis. RESULTS: Of the 87,166 patients diagnosed with non-Hodgkin's
      lymphoma during the 13-year period between 1992 and 2004, 2459 (2.8%) had
      confirmed MCL. The overall incidence of MCL (per 100,000) was 0.55, which
      increased with age: 0.07 in patients aged <50 years, 2.97 in patients aged 70 to
      79 years, and 2.78 in those aged > or =80 years. The age-adjusted incidence rate
      increased from 0.27 of 100,000 in 1992 to 0.69 of 100,000 in 2004, and the annual
      percent change was 5.87% (P < .05). The median age at diagnosis was 68 years. The
      incidence of MCL was higher in men (0.84 of 100,000) than in women (0.34 of
      100,000) (P < .05), and was higher in Caucasians (0.61 of 100,000) than in
      African Americans (0.32 of 100,000). Late-stage (III-IV) MCL was diagnosed in
      74.6% of patients. There were significant geographic variations noted (P < .05).
      CONCLUSIONS: The incidence of MCL increased from 1992 to 2004, and was
      significantly higher in men, in Caucasians, and patients aged > or =50 years.
      Most patients were diagnosed with late-stage MCL, and there also were
      considerable geographic variations observed in incidence rate.

PMID- 18615508
TI  - High elevated ferritin levels and the diagnosis of HLH/Sepsis/SIRS/MODS/MAS.

PMID- 18615507
TI  - Vincristine pharmacokinetics in children with Down syndrome.
AB  - Children with Down syndrome (DS), who represent about 2% of childhood acute
      lymphoblastic leukemia, have inferior prognosis compared to non-DS children. For
      vincristine (and many other anticancer agents) pharmacokinetic data are scant or
      missing, and there is considerable uncertainty about the optimal dosing of drugs
      to patients with DS. We studied vincristine pharmacokinetics on treatment day one
      in six children with DS and compared to 92 non-DS children. No differences were
      found. Thus, we found no rationale for dose reduction of vincristine in DS
      children from a strictly pharmacokinetic point of view.

PMID- 18615510
TI  - Biosorption of lead and nickel by biomass of marine algae.
AB  - Screening tests of different marine algae biomas types revealed a high passive
      biosorptive uptake of lead up to 270 mg Pb/g of biomass in some brown marine
      algae. Members of the order Fucales perfomed particularly well in this descending
      sequence: Fucus > Ascophyllum > Sargassum. Although decreasing the swelling of
      wetted biomass particles, their reinforcement by crosslinking may significantly
      affect the biosorption performance. Lead uptakes up to 370 mg Pb/g were observed
      in crosslinked Fucus vesiculosus and Ascophyllum nodosum. At low equilibrium
      residual concentrations of lead in solution, however, ion exchange resin
      Amberlite IR-120 had a higher lead uptake than the biosorbent materials. An order
      of-magnitude lower uptake of nickel was observed in all of the sorbent materials
      examined. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615511
TI  - Cadmium removal in a biosorption column.
AB  - New biosorbent material derived from a ubiquitous brown marine alga Ascophyllum
      nodosum has been examined in packed-bed flow-through sorption columns. It
      effectively removed 10 mg/L of cadmium down to 1.5 ppb levels in the effluent,
      representing 99.985% removal. The experimental methodology used was based on the
      early Bohart and Adams sorption model, resulting in quantitative determination of
      the characteristic process parameters which can be used for performance
      comparison and process design. An average metal loading of the biosorbent (N(0))
      determined was 30 mg Cd/g, corresponding closely to that observed for the batch
      equilibrium metal concentration of 10 mg Cd/L. The critical bed depth (D(min))
      for the potable water effluent quality standard (0.005 mgg Cd/L) varied with the
      column feed flow rate (2.4 to 9.6 L/h . cm(2)) from 20 to 50 cm. The sorption
      column mass transfer and dispersion coefficients were determined, which are also
      required for solving the sorption model equations. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615512
TI  - Enzymatic catalysis in heterogenous mixtures of substrates: The role of the
      liquid phase and the effects of "Adjuvants".
AB  - The physicochemical mechanism of protease-catalyzed peptide synthesis in
      heterogenous etuectic mixtures of substrates has been examined by a combination
      of microscopic techniques. Using a number of model reactions of dipeptide amide
      synthesis, it was determined that liquid phase catalysis was mostly, if not
      exclusively, responsible for the observed conversion of substrates. Furthermore,
      the formation of liquid or semiliquid eutectics was an important requirement for
      the occurrence of those reactions where both substrates were solids in the pure
      state. The addition of small quantities of hydrophilic solvents (adjuvants) often
      resulted in significat improvements in the rates and yields of the reactions.
      This was due to the ability of these adjuvants to promote the formation of
      eutectics, thereby increasing the proportion, as well as affecting the
      composition the properties, as well as affecting the composition and properties
      of the liquid phase. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615513
TI  - Protease-catalyzed synthesis of oligopeptides in heterogenous substrate mixtures.
AB  - A systematic study of enzymatic peptide synthesis in heterogeneous substrate
      mixtures was carried out, with the aim of establishing the preparative scope of
      this methodology. Semiliquid eutectics were obtained with various combinations of
      neutral, acidic, and basic amino acid derivatives, in the presence or absence of
      adjuvants. A range of serine cysteine, and metalloproteases readily catalyzed the
      formation of the required dipeptides under these conditions. The synthetic
      usefulness of the approach was demonstrated by the sequential and convergent
      synthesis of derivatives of a number of bioactive di-, tri-, and pentapeptides,
      including aspartame, sweet lysine peptide, kyotorphin amide, ACE-inhibiting and 
      immunoactive tripeptides, and Leu-enkephalin amide, with overallyields of 21% to
      84% and productivities of 0.13 to 0.75 g/g being obtained. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18615514
TI  - Synthesis of AcPheLeuNH(2) by alpha-chymotrypsin in TTAB reversed micelles:
      Application of response surface methodology to the optimization of the system.
AB  - The influence of the long chain alcohols, hexanol, octanol, and decanol, as
      cosurfactants of the reverse micellar system of tetradecyltrimethylammonium
      bromide on the alpha-chymotrypsin-mediated AcPheLeuNH(2) synthesis was studied.
      The effect of temperature, buffer molarity, pH, and substrate concentration was
      also evaluated. The enzyme was chemically modified and the effect of this
      modification upon the enzyme activity was also analyzed. Octanol allowed a higher
      activity for both enzyme forms. The peptide synthesis/substrate hydrolysis ratio
      is independent of the long chain alcohol used. The chemical modification
      decreases the alpha-chymotrypsin activity under the system conditions studied,
      but increases the initial velocity of peptide synthesis relative to the ester
      substrate hydrolysis. The response surface methodology was applied to optimize
      the dipeptide synthesis in the system containing octanol as cosurfactant. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18615515
TI  - Cybernetic model for synthesis of poly-beta-hydroxybutyric acid in Alcaligenes
      eutrophus.
AB  - The pathway of poly-beta-hydroxybutyric acid (PHB) exhibits a mode of
      transcriptional control induced by environmental stress. A new cybernetic model
      for coordinated regulation of stress-induced metabolism was developed to predict
      the growth and the synthesis of PHB in Alcaligenes eutrophus. A plausible
      objective for this control is optimization of acetyl-CoA utilization so that the
      cells have a high degree of flexibility in their catabolism. The state equation
      for key protein synthesis was assumed to have a dependence on the nonlinear
      control variable. The proposed model can demonstrate the mixed-growth-associated
      synythesis of PHB. Reported unstructured models were compared statistically with
      the result of the simulation derived from the proposed model using the
      experimental data of this study and the literature. The proposed model appeared
      to provide an excellent description for the overall fermentation range. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18615516
TI  - The effects of pH and ionic strength on the partitioning of four proteins in
      reverse micelle systems.
AB  - Four proteins with different physicochemical properties have been partitioned in
      reversed micelle systems: thaumatin, ribonuclease A, soybean trypsin inhibitor,
      and alpha-lactalbumin. The organic phase was formed by sodium salt (AOT) in
      isooctane, and the aqueous phase contained KCl, KBr, MgCl(2), or NaCl. Aqueous
      phase pH was varied between 2 and 13 and ionic strength from 0.1 to 1.0 M. Small
      changes in pH [around the isoelecric point (pl)] were found to influence the
      solubilization of ribonuclease A and trypsin inhibitor, but for thaumatin the pH
      change necessary to affect partition was much greater as a consequence of the
      difference in net charge (titration curves) of these protein molecules as pH
      changes. The type of ions present in the system was also a determining factor for
      partition; the larger ions (K(+)) produced more electrostatic screening and hence
      less protein solubilization than the smaller ions (Na(+)). With changes in ionic
      strength surface hydrophobicity was a dominant factor affecting solubilization of
      thaumatin in NaCl-containing systems at high pH. Charge distribution and
      hydrophobicity are thought to be important parameters when partitioning the
      protein alpha-lactalbumin. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615517
TI  - Quantitative in vivo nuclear magnetic resonance studies of hybridoma metabolism.
AB  - Carbon-13 nuclear magnetic resonance (NMR) spectroscopy was used to study the
      metabolism of a murine hybridoma cell line at two feed glutamine concentrations,
      4.0 and 1.7 mM. Carbon-13 labeling patterns were used in conjunction with
      nutrient uptake rates to calculate the metabolic fluxes through the glycolytic
      pathway, the pentose shunt, the malate shunt, lipid biosynthesis, and the
      tricarboxylic acid (TCA) cycle. Decreasing the feed glutamine concentration
      significantly decreased glutamine uptake but had little effect on glucose
      metabolism. A significant incrase in antibody productivity occurred upon
      decreasing the feed glutamine level. The increased antibody productivity in
      concert with decreased glutamine uptake and no apparent change in glucolytic
      metabolism suggests that antibody production was not energy limited. Metabolic
      flux calculations indicate that (1) approximately 92% of the glucose consumed
      proceeds directly through glycolysis with 8% channeled through the pentose shunt;
      (2) lipid biosynthesis appears to be greater than malate shunt activity; and (3)
      considerable exchange occurs between TCA cycle intermediates and amino acid
      metabolic pools, leading to substantial loss of (13)C label from the TCA cycle.
      These results illustrate that (13)NMR spectroscopy is a powerfulf tool in the
      calculation of metabolic fluxes, particularly for exchange pathways where no net
      flux occurs. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615518
TI  - Enzymatic synthesis of alkyl beta-D-xylosides by transxylosylation and reverse
      hydrolysis.
AB  - The Trichoderma reesei beta-xylosidase (EC 3.2.1.37) is used to catalyze the
      production of alkyl beta-D-xyloside. Two general methods of production are tested
      and compared using the same enzyme: transglycosylation and reverse hydrolysis.
      Using both methods, primary, secondary, and tertiary alcohols are studied as
      acceptors. In kinetically controlled process (transglycosylation), the chosen
      donor is methyl beta-D-xyloside and primary, secondary, and tertiary alkyl
      alcohols are accepted. In the equilibrium-controlled synthesis, the donor is
      xylose whereas acceptors are only primary and secondary alcohols. The influence
      of the donor concentration is investigated in both processes. The yields of the
      kinetically controlled reactions are higher compared with those of the
      equilibrium-controlled synthesis. The specificity of the beta linkage is
      confirmed by proton nuclear magnetic resonance ((1)H NMR) analysis. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18615519
TI  - Solvation of CBZ-amino acid nitrophenyl esters in organic media and the kinetics
      of their transesterification by subtilisin.
AB  - Subtilisin Carlsberg adsorbed on silica particles has been used to catalyze the
      transesterification of CBZ-Ala-ONp and CBZ-Leu-ONp with 1-butanol in organic
      systems preequilibrated to water activity of 0.93. Initial reaction rates are
      conveniently followed by extraction of the released nitrophenol into an alkaline
      aqueous phase. Kinetic parameters were determined for varied ester concentrations
      in toluene, isopropyl ether, and hexane. The effect of solvent on substrate
      solvation was determined by solubility measurements. Much of the observed effect
      of solvent on V(m)/K(m) may be accounted for by solvation differences. The
      residual effect of solvent on K(m), after discounting solvation differences, is
      completely opposite to the apparent trend. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615520
TI  - Adsorption of BSA on strongly basic chitosan: Equilibria.
AB  - Equilibrium isotherms for adsorption of bovine serum albumin (BSA) on a new
      adsorbent, a strongly basic crosslinked chitosan (Chitopearl 2503), which is hard
      and is not compressed by pressure in a column, have been presented and compared
      with diethylaminoethyl (DEAE) Sepharose Fast Flow (hard gel). In Chitopearl 2503,
      when only buffer existed in the BSA solution, the isotherm was not affected by
      the initial concentration of BSA but it was affected by pH considerably. The
      isotherm was favorable when pH >/= pl ( congruent with 4.8). When NaCl existed in
      the BSA solution, the amount of BSA absorbed on the resin decreased with
      increasing concentration of NaCl. When the concentration of NaCl was 200
      mol/m(3), the resin did not adsorb BSA at all. The equilibrium data were
      correlated by the Langmuir equation reasonably well. The BSA may be adsorbed
      mainly by electrostatic attraction between negatively charged BSA and positively
      charged quanternary ammonium groups at pH > pl and by protonation reaction of the
      primary ammonium groups by weak acid groups of BSA at pH = pl. These are
      confirmed by measuring the amount of inorganic ion exchanged for BSA. In DEAE
      Sepharose Fast Flow, the isotherm was favorable when pH > pl but unfavorable ar
      pH = pl. The saturation capacity of BSA on Chitopearl 2503 is about 1.3 to 2.2
      times larger than that on DEAE Sepharose Fast Flow. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615521
TI  - Crossflow filtration of yeast broth cultivated in molasses.
AB  - A broth of yeast cells cultivated in molasses was crossfiltered with a thin
      channel module. The permeation flux gradually decreased at a constant cell
      concentration. The flux was much lower than that obtained for yeast broth
      cultivated in yeast extract, polypeptone, and dextrose (YPD) medium during the
      filtration. The flux did not depend on the membrane pore size (0.45 to 5 mum).
      The steady-state flux was one-twentieth that calculated for a cake filtration
      mode from the amount of cake per unit filtration area and the specific resistance
      of the cake measured in a dead-end filtration apparatus. The lower flux was due
      to small particles (most of which were less than 1 mum in diameter) in the
      molasses. The mehanism of crossflow filtration of broths of yeast cells
      cultivated in molasses was clarified by analysis of the change in flux with time
      and observations with scanning electron microscopy. At the initial stage of
      crossflow filtration the yeast cells and particles from the molasses were
      deposited on the membrane to form the molasses were deposited on the membrane to
      form a cake in a similar way to dead-end filtration. After the deposition of
      cells onto the membrane ceased, the fine particles from molasses formed a thin
      layer, which had higher resistance than the cake formed next to the membrane. The
      backwashing method was effective to increase the flux. The flux increased low
      when the pore size was 0.45 to 0.08 mum, but using larger pores of 3 to 5 mum it
      returned almost to the bases line. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615522
TI  - Stabilizing effect of amphiphilic excipients on the freeze-thawing and freeze
      drying of lactate dehydrogenase.
AB  - The effects of amphiphilic excipients on the inactivation of lactate
      dehydrogenase (LDH) during freeze-thawing and freeze-drying were studied. Some
      amphiphilic excipients such as hydroxypropyl-beta-cyclodextrin (HP-beta-CD),
      CHAPS, polyethylene glycol (PEG) 3350, and sucrose fatty acid monoester prevented
      LDH inactivation during freeze-thawing and freeze-drying at a lower concentration
      than sugars and amino acids. Polyoxyethylene 9 lauryl ether and PEG 400 protected
      LDH during freeze-thawing but not during freeze-drying. The buffer concentration
      of the solution to be freeze-dried (10, 50, and 200 mM) affected the stabilizing
      effect of trehalose, but not that of HP-beta-CD. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615523
TI  - Synthesis of dipeptide precursors with an immobilized thermolysin in ethyl
      acetate.
AB  - N-(Benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-AspPheOMe), a
      precursor of the aspartame, and N-(benzyloxycarbonyl)-L-phenylalanyl
      Lphenylalanine methyl ester (Z-PhePheOMe) were synthesized from the respective
      amino acid derivatives with an immobilized thermolysin (EC 3.4.24.4) in ethyl
      acetate. Various factors affecting the synthesis of these dipeptide precursors
      were clarified. The initial synthetic rate was the highest at the water content
      of 3.5% for both reactions. The substrate concentration dependencies of the
      initial synthetic rate of Z-AspkPheOMe and Z-PhePheOMe with the immobilized
      enzyme in ethyl acetate were different from those in an aqueous buffer solution
      saturated with ethyl acetate but similar to those in the aqueous/organic biphasic
      system using the free enzyme. Particularly, the initial synthetic rate of Z
      AspPhOMe increased in order higher than first order with respect to the
      concentration of L-phenylalanine methyl ester (PheOMe), whereas it decreased
      sharply with the concentration of N-(benzyloxycarbonyl)-L-aspartic acid (Z-Asp).
      Such kinetic behavior could be explained by regarding the inside of the
      immobilized enzyme as being a biphasic mode composed from the organic phase and
      aqueous phase where the enzymatic reaction takes place. The reaction in the
      aqueous/organic biphasic system using the free enzyme could be simulated by
      taking into consideration the partition of the substrate and the initial rate of
      synthesis in the aqueous buffer saturated with ethyl acetate. Based on this
      analysis, the rate of reaction with the immobilized enzyme in ethyl acetate could
      also be predicted. Z-AsPheOMe and Z-PhePheOMe were synthesized by the fed-batch
      method where the acid component of the substrate was intermittently added during
      the course of reaction and by the batch method. In the synthesis of Z-AspPheOMe,
      the synthetic rate and maximum yield of reaction as well as the stability of the
      immobilized enzyme were higher in the fed-batch reaction than those in the batch
      reaction. In the synthesis of Z-PhePheOMe, the results obtained by both methods
      were similar. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615524
TI  - Synthesis of aspartame precursor with an immobilized thermolysin in tert-amyl
      alcohol.
AB  - N-(Benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-AspPheOMe), a
      precursor of the synthetic sweetner asparatame, was synthesized from N
      (benzyloxycarbolyl)-L-aspartic acid (Z-Asp) and L-phenylalanine methyl ester
      (PheOMe) with an immobilized thermolysin in various organic solvents. We found
      that in tert-amyl alcohol containing a small amount of water the immobilized
      enzyme showed a high activity comparble to that in ethyl acetate with quite a
      high stability. The immobilized enzyme was fully stable up to 70 degrees C in
      tert-amyl alcohol in the absence of the subatrate, and up to 50 degrees C in the
      presence of the substrate. The high stability in the presence of the substrate
      was found due to the fact that the release of calcium ions, the stabilizing
      factor of thermolysin, is suppressed.The substrate concentration dependence of
      the initial synthetic rate with the immobilized enzyme was quite different from
      that with the free enzyme in the biphasic system, in contrast to that in ethyl
      acetate. Finally, Z-AspPheOMe was continuously synthesized in a column reactor
      using 200 mM PheOMe and 120 mM Z-Asp as the substrate for over 300 h at 45
      degrees C and a space velocity of 1 h(-1) without any loss of acivity. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18615525
TI  - Continuous propionate production from whey permeate using a novel fibrous bed
      bioreactor.
AB  - Continuous production of propionate from whey lactose by Propionibacterium
      acidipropionici immobilized in a novel fibrous bed bioreactor was studied. In
      conventional batch propionic acid fermentation, whey permeate without nutrient
      supplementation was unable to support cell growth and failed to give satisfactory
      fermentation results for over 7 days. However, with the fibrous bed bioreactor, a
      high fermentation rate and high conversion were obtained with plain whey permeate
      and de-lactose whey permeate. About 2% (wt/vol) propionic acid was obtained from
      a 4.2% lactose feed at a retention time of 35 to 45 h. The propionic acid yield
      was approximately 46% (wt/vol) from lactose. The optimal pH for fementation was
      6.5, and lower fermentation rates and yields were obtained at lower pH values.
      The optimal temperature was 30 degrees C, but the temperature effect was not
      dramatic in the range of 25 to 35 degrees C. Addition of yeast extract and
      trypticase to whey permeate hastened reactor startup and increased the
      fermentation rate and product yields, but the addition was not required for long
      term reactor performance. The improved fermentation results with the immobilized
      cell bioreactor can be attributed to the high cell density, approximately 50 g/L,
      attained in the bioreactor, Cells were immobilized by loose attachement to fiber
      surfaces and entrapment in the void spaces within the fibrous matrix, thus
      allowing constant renewal of cells. Consequently, this bioreactor was able to
      operate continuously for 6 months without encountering any clogging,
      degeneration, or contamination problems. Compared to conventional batch
      fermentors, the new bioreactor offers many advantages for industrial
      fermentation, including a more than 10-fold increase in productivity, acceptance
      of low-nutrient feedstocks such as whey permeate, and resistance to
      contamination. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615526
TI  - Effects of biofilm structures on oxygen distribution and mass transport.
AB  - Aerobic biofilms were found to have a complex structure consisting of microbial
      cell clusters (discrete aggregates of densely packed cells) and interstitial
      voids. The oxygen distribution was strongly correlated with these strutures. The
      voids facilitated oxygen transport from the bulk liquid through the biofilm,
      supplying approximately 50% of the total oxygen consumed by the cells. The mass
      transport rate from the bulk liquid is influenced by the biofilm structure; the
      observed exchange surface of the biofilm is twice that calculated for a simple
      planar geometry. The oxygen diffusion occurred in the direction normal to the
      cluster surfaces, the horizontal and vertical components of the oxygen gradients
      were of equal importance. Consequently, for calculations of mass transfer rates a
      three-dimensional model is necessary. These findings imply that to accurately
      describe biofilm activity, the relation between the arrangement of structural
      components and mass transfer must be undrstood. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615527
TI  - Phase fluorometric sterilizable optical oxygen sensor.
AB  - We report here on a low-cost, optical oxygen sensor as an attractive alternative
      to the widely used amperometric Clark-type oxygen electrode for measuring
      dissolved oxygen tensions in cell cultures and bioreactor. Our sensor is based on
      the defferential quenching of the fluorescence lifetime of chromophore in
      response to the partial pressure of oxygen. This is measured as a phase shift in
      fluorescence emission from the chromophore due to oxygen quenching when excited
      by an intensity modulated beam of light. In this article we demonstrate the
      advantages of lifetime-based optical methods over both intensity based optical
      methods and amperometric electrodes. Our sensor is particularly suitable for
      measuring dissolved oxygen in bioreactors. It is autoclavable, is free of
      maintenance requirements, and solvents the problems of long-term stability,
      calibration drifts, and reliable measurement of low oxygen tensions in dense
      microbial cultures that limit the utility of Clark-type elcectordes. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18615528
TI  - Metabolic engineering of Pseudomonas putida for the simultaneous biodegradation
      of benzene, toluene, and p-xylene mixture.
AB  - For the complete biodegradation of a mixture of benzene, toluene, and p-xylene
      (BTX), a critical metabolic step that can connect two existing metabolic pathways
      of aromatic compounds (the tod and the tol pathways) was determined. Toluate-cis
      glycol dehydrogenase in the tol pathway was found to attack benzene-cis-glycol,
      toluene-cis-glycol, and p-xylene-cis-glycol, which are metabolic intermediates of
      the tod pathway. Based on this observation, a hybrid strain, Pseudomonase putida
      TB101, was constructed by introduction of the TOL plasmid pWW0 into P. putida
      F39/D, a derivative of P. putida F1, which is unable to transform cis-glycol
      compounds to corresponding catechols. The metabolic flux of BTX into the tod
      pathway was redirected to the tol pathway at the level of cis-glycol compounds by
      the action of toluate-cis-glycol dehydrogenase in P. putida TB101, resulting in
      the simultaneous mineralization of BTX mixture without accumulation of any
      metabolic intermediates. The profile of specific degradation rates showed a
      similar pattern as that of the specific growth rate of the microorganism, and the
      maximum specific degradation rates of benzene, toluene, and p-xylene were
      determined to be about 0.27, 0.86, and 2.89 mg/mg biomass/h, respectively. P.
      putida TB101 is the first reported microorganism that mineralizes BTX mixture
      simultaneously. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615529
TI  - Co-immobilized Nitrosomonas europaea and Nitrobacter agilis cells: validation of
      a dynamic model for simultaneous substrate conversion and growth in kappa
      carrageenan gel beads.
AB  - A dynamic model for two microbial species immobilized in a gel matrix is
      presented and validated with experiments. The model characterizes the
      nitrification of ammonia with Nitrosomonas europaea and Nitrobacter agilis co
      immobilized in K-carrageenan gel beads. The model consists of kinetic equations
      for the microorganisms and mass transfer equations for the substrates and
      products inside and outside the gel beads. The model predicts reactor bulk
      concentrations together with the substrate consumption rate, product formation,
      and biomass growth inside the gel beads as a function of time. A 50-day
      experiment with immobilized cells in a 3.3-dm(3) air-lift loop reactor was
      carried out to validate the model. The parameter values for the model were
      obtained from literature and separate experiments. The experimentally determined
      reactor bulk concentrations and the biomass distribution of the two
      microorganisms in the gel beads were well predicted by the model. A sensitivity
      analysis of the model for the given initial values indicated the most relevant
      parameters to be the maximum specific growth rate of the microorganisms, the
      diffusion coefficient of oxygen, and the radius of the beads. The dynamic model
      provides a useful tool for further study and possible control of the
      nitrification process. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615530
TI  - Stoichiometric analysis of animal cell growth and its application in medium
      design.
AB  - Animal cell cultivation in vitro has been studied for more than 40 years.
      However, the culture medium composition has not been designed on the basis of the
      stoichiometric nutritional demands for animal cell growth. In this article, a
      model was developed to study the stoichiometric demands for nutrients (including
      glucose, 20 amino acids, and 10 vitamins)for the synthesis of cell mass and
      product. The coefficients for these nutrients in the stoichiometric equation
      governing animal cell growth were determined based on cell composition. In
      addition, a detailed analysis of the nutrients' roles in the synthesis of cell
      mass and product was also performed. Applications of the stoichiometric analysis
      in animal cell cultivation, such as culture medium design, supplemental medium
      formulation, and feeding strategy will also be discussed. The stoichiometric
      analysis can be potentially employed to analyze results from animal cell
      cultures, to improve the performance of culture processes, and to design new
      process rationally. It can also help to provide a better understanding of animal
      cell metabolism. Simplifications on the cellular energy metabolism were made in
      order to simplify the model and to provide the preliminary bases to test the
      process performance. However, this could introduce inaccuracies for the model and
      results in errors in the calculations of glucose and glutamine concentrations
      when employed in medium design. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615531
TI  - Fed-batch cultivation of animal cells using different medium design concepts and
      feeding strategies.
AB  - In animal cell cultivation, cell density and product concentration are often low
      due to the accumulation of toxic end-products such as ammonia and lactate and/or
      the depletion of essential nutrients. A hybridoma cell line (CRL-1606) was
      cultivated in T-flasks using a newly devised medium feeding strategy. The goals
      were to decrease ammonia and lactate formation by the design of an initial medium
      which would provide a starting environment to achieve optimal cell growth. This
      was followed by using a stoichiometric equation governing animal cell growth and
      then designing a supplemental medium for feeding strategy used to control the
      nutritional environment. The relationship between the stoichiometric demands for
      glutamine and nonessential amino acids was also studied. Through stoichiometric
      feeding, nutrient concentrations were controlled reasonably well. Consequently,
      the specific production rate of lactate was decreased by fourfold compared with
      conventional fed-batch culture and by 26-fold compared with conventional batch
      culture. The specific production rate of ammonia was decreased by tenfold
      compared with conventional fed-batch culture and by 50-fold compared with
      conventional batch culture. Most importantly, total cell density and monoclonal
      antibody concentration were increased by five- and tenfold respectively, compared
      with conventional batch culture. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615532
TI  - Communication to the editor. Application of the cross-regulation system as a
      metabolic switch.
AB  - The ability to switch metabolic flow from one pathway to another at a desired
      point in a bioprocess expands the horizons of metabolic engineering. Such an
      externally inducible switch can be realized by embedding synthetic operons behind
      tow corss-regulated promoters. This results in coordinated cessation of
      transcription of one operon while transcription of a second operon is
      simultaneously activated. The ability to effect such coordinated and inverse
      control of transcription of two operons has been illustrated experimentally using
      a model construct containing two different reporter genes, Vitreoscilla
      hemoglobin (VHb) and chloramphenicol acetyltransferase (CAT), fused to lambdaP(L)
      and tac promoters, respectively, along with corresponding repressor genes in a
      cross-regulation configuration. Only VHb production was observed preinduction,
      and postinduction only CAT was produced. The framework presented here and its
      obvious extensions can be used with different combinations of promoter systems
      and synthetic operon constructs to achieve complicated metabolic flux regulation
      in diverse host. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615533
TI  - Structure-activity relationships for hepatocyte toxicity and electrophilic
      reactivity of alpha,beta-unsaturated esters, acrylates and methacrylates.
AB  - Covalent binding of reactive electrophiles to cellular targets is a molecular
      interaction that has the potential to initiate severe adverse biological effects.
      Therefore, electrophile reactivity towards biological nucleophiles could serve as
      an important correlate for toxic effects such as hepatocyte death. To determine
      if reactivity correlates with rat hepatotoxicity, alpha,beta-unsaturated esters,
      consisting of acrylates and methacrylates, that are inherently electrophilic and
      exhibit widely varying degrees of reactivity were investigated. Reactivity was
      measured using simple assays with glutathione and butylamine as surrogates for
      soft thiol and hard amino biological nucleophile targets. A linear relationship
      was observed between hepatotoxicity and thiol reactivity only, while no amine
      reactivity was observed. Structure-activity relationships were also investigated,
      with results showing toxicity was well modeled by electronic parameters E(LUMO)
      and partial charge of the carbon atoms in the reactive center. No relationship
      was observed between toxicity and logP. These results suggest that differences in
      hepatocyte toxicity of acrylates and methacrylates can be related to their
      electrophilic reactivity which corresponds to their ability to deplete GSH and
      protein thiols.

PMID- 18615535
TI  - Spatiotemporal distribution of proteoglycans in the developing rat's barrel field
      and the effects of early deafferentation.
AB  - The isolectin Vicia villosa B(4) (VV) selectively recognizes N-acetyl
      galactosamine-terminal glycoconjugates that form perineuronal nets (PNNs) around
      a subset of neurons in the cerebral cortex. PNNs are thought to participate in
      the guidance of incoming thalamic axons and in the posterior stabilization and
      maintenance of synaptic contacts. Here we examine the spatial and temporal
      distribution of biotinylated VV in tangential sections through layer IV of the
      posteromedial barrel subfield in the primary somatosensory cortex (PMBSF) of rats
      ranging from postnatal day (P)3 to P60, which underwent unilateral
      deafferentation of whiskers at birth. In the afferented hemisphere, labeling
      first appears at P5, with a diffuse distribution, probably associated with
      neuropil, inside PMBSF barrels. VV distribution remains diffuse during the
      following week, and declines around P17. From P24 onward, however, proteoglycans
      form PNNs around cell bodies preferentially localized in septal regions of the
      PMBSF. In the contralateral, deafferented PMBSF the diffuse labeling also appears
      on P5, but first develops into elongated, homogeneous stripes, which disappear
      after P24, leaving only scattered cell bodies along layer IV. Our results
      indicate that proteoglycans appear simultaneous to barrel formation in the
      developing rat while segregation of PNNs to septal cells might be driven by
      afferent activity.

PMID- 18615536
TI  - A modern regimen of pre-operative concurrent chemo-radiation therapy in locally
      advanced rectal cancer.
AB  - PURPOSE: To evaluate the efficacy and toxicity of preoperative concurrent
      capecitabine and radiotherapy in the treatment of resectable locally advanced
      rectal cancer (LARC). MATERIALS AND METHODS: We conducted a phase II trial to
      assess pathological complete response, tumor downstaging, toxicity and survival
      of capecitabine (825 mg/m(2) orally, twice daily) with radiotherapy (50.4 Gy/28
      fractions) in 31 patients with LARC (cT3/T4 or N+) staged by endoscopic
      ultrasound (EUS). RESULTS: Median age was 53 years; with M:F ratio of 1:1.58;
      77.4% had Eastern Cooperative Oncology Group performance status of 1. EUS showed
      that 67.7% of tumors were T3, 19.4% were T4, and 58% were node positive. Of 30
      patients who had surgery, 6.5% achieved pathological complete remission (pCR).
      Tumor and nodal downstaging were achieved in 53.9% and 50% of patients,
      respectively. Grade 3/4 toxicities were mainly diarrhea (35.5%) and proctitis
      (32.3%). Sphincter preservation was achieved in 4/21 (15%) of patients initially
      planned for abdominoperineal resection. The median follow-up was 46 months
      (Range: 1.47-63.9), and the 3-year disease-free and overall survival were 59.8%
      and 76.6%, respectively. CONCLUSION: Capecitabine given concurrently with
      radiation therapy is generally well tolerated, and proved to be an effective
      radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer,
      yielding results comparable to those reported with 5-FU.

PMID- 18615534
TI  - Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2
      expression after spinal contusion in rats.
AB  - Demyelination and oligodendrocyte loss following spinal cord injury (SCI) are
      well documented. Recently, we showed oligodendrocyte progenitor cell (OPC)
      accumulation and robust oligodendrocyte genesis occurring along SCI lesion
      borders. We have since begun investigating potential mechanisms for this
      endogenous repair response. Here, we examined ciliary neurotrophic factor (CNTF)
      and fibroblast growth factor-2 (FGF-2) expression, because both factors alter
      progenitor proliferation and differentiation and are increased in several CNS
      disorders. We hypothesized that CNTF and FGF-2 would increase after SCI,
      especially in regions of enhanced oligogenesis. First, CNTF protein was
      quantified using Western blots, which revealed that CNTF protein continually rose
      through 28 days post injury (dpi). Next, by using immunohistochemistry, we
      examined the spatiotemporal expression of CNTF in cross-sections spanning the
      injury site. CNTF immunoreactivity was observed on astrocytes and
      oligodendrocytes in naive and contused spinal cords. Significantly increased CNTF
      was detected in spared white and gray matter between 5 and 28 dpi compared with
      uninjured controls. By 28 dpi, CNTF expression was significantly higher along
      lesion borders compared with outlying spared tissue; a similar distribution of
      phosphorylated STAT3, a transcription factor up-regulated by CNTF and to a lesser
      extent FGF-2, was also detected. Because CNTF can potentiate FGF-2 expression, we
      examined the distribution of FGF-2+ cells. Significantly more FGF-2+ cells were
      noted along lesion borders at 7 and 28 dpi. Thus, both CNTF and FGF-2 are present
      in regions of elevated OPC proliferation and oligodendrocyte generation after SCI
      and therefore may play a role in injury-induced gliogenesis.

PMID- 18615537
TI  - A dual system of intercellular calcium signaling in glial nets associated with
      lanceolate sensory endings in rat vibrissae.
AB  - The lanceolate sensory endings that form palisades around the hair follicle
      associate with networks of branched Schwann cells. To define the properties of
      these glial networks as possible conduits of Ca2+ signals, lanceolate endings
      isolated from rat vibrissae were observed by confocal microscopy while the
      signaling was locally activated by mechanical stimulation. Intercellular coupling
      by gap junctions was also assessed by a technique employing fluorescence recovery
      after photobleaching (FRAP) and by transmission electron microscopy (TEM).
      Results showed that the glial Ca2+ signals can spread among the arrays of
      lanceolates in two forms: rapid signals that originate in individual Schwann
      processes covering the lanceolate axon terminals around the locus of mechanical
      stimulation, and delayed ones that travel from the stimulation locus through
      cytoplasmic arborization of the primarily activated cell to the adjacent cell
      processes. The former signaling was suppressed by the antipurinergic agents
      suramin and apyrase, whereas the latter was sensitive to the gap junction blocker
      carbenoxolon. FRAP experiments and TEM observations corroborated the presence of
      gap junction communications between the Schwann processes of different cell
      origins. These findings show that, in the Schwann networks, purinergically
      induced Ca2+ signals and those dependent on gap junctions are propagated in their
      own spatiotemporal patterns to constitute two distinct forms of communication
      among the mechanoreceptor palisades.

PMID- 18615538
TI  - No association between a polymorphic variant of the IRS-1 gene and prostate
      cancer risk.
AB  - OBJECTIVE: Insulin receptor substrate-1 (IRS-1) acts as a docking protein between
      the insulin-like growth factor-1 (IGF-1) receptor and intracellular signaling
      molecules in the IGF-1 signaling pathway. Accumulating data support a role of IGF
      1 in prostate carcinogenesis. We assessed the influence of the most common IRS-1
      gene polymorphism (Gly972Arg) on prostate cancer risk, alone and in combination
      with IGF-1 and other components in the IGF-1 signaling pathway. MATERIALS AND
      METHODS: In a nested case-control study within the Physicians' Health Study, the
      IRS-1 polymorphism was assayed from prospectively collected samples from 564
      incident prostate cancer cases and 758 controls matched on age and smoking. We
      calculated relative risks (RR) and 95% confidence intervals (CI) using
      conditional logistic regression. RESULTS: Among the controls, 0.8% were
      homozygous (AA) and 12% were heterozygous (GA) for the polymorphic allele. There
      was no association between carriage of the A allele and total prostate cancer
      risk (RR = 1.1 95% CI = 0.8-1.5), advanced disease (stage C or D or lethal
      prostate cancer, RR = 1.3 95% CI = 0.8-2.3), or plasma IGF-1 levels. We explored
      possible interactions with body mass index and components in the IGF-1 pathway
      including IGFBP3, PI3k, and PTEN but none of these factors influenced the
      relation between IRS-1 genotype and prostate cancer risk. CONCLUSIONS: Our data
      do not support an association between carriage of the variant IRS-1 gene and
      prostate cancer risk.

PMID- 18615540
TI  - Misgenotyping of dopamine receptor D1 gene -48A/G polymorphism.

PMID- 18615539
TI  - Contralateral corticothalamic projections from MI whisker cortex: potential route
      for modulating hemispheric interactions.
AB  - Rat whisking behavior is characterized by high amounts of bilateral coordination
      in which whisker movements on both sides of the face are linked. To elucidate the
      neural substrate that might mediate this bilateral coordination, neuronal tracers
      were used to characterize the bilateral distribution of corticothalamic
      projections from primary motor (MI) cortex. Some rats received tracers in the MI
      whisker region, whereas others received tracers in the MI forepaw region. The MI
      whisker region projects bilaterally to the anteromedial (AM), ventromedial (VM),
      and ventrolateral (VL) nuclei, and to parts of the intralaminar nuclei. By
      contrast, the MI forepaw region sends virtually no projections to the
      contralateral thalamus. Consistent with these findings, bilateral injections of
      different tracers into the MI whisker region of each hemisphere produced tracer
      overlap on both sides of the thalamus. Furthermore, MI whisker projections to the
      contralateral thalamus terminate in close proximity to the thalamocortical
      neurons that project to the MI whisker region of that contralateral hemisphere.
      The terminal endings of the contralateral corticothalamic projections contain
      small synaptic varicosities and other features that resemble the modulator
      pathways described for other corticothalamic projection systems. In addition,
      tracer injections into AM, VM, and VL revealed dense clusters of labeled neurons
      in layer VI of the medial agranular (Agm) zone, which corresponds to the MI
      whisker region. These results suggest that projections from the MI whisker region
      to the contralateral thalamus may modulate the callosal interactions that are
      presumed to play a role in coordinating bilateral whisking behavior.

PMID- 18615542
TI  - Comparative study of the distribution of the alpha-subunits of voltage-gated
      sodium channels in normal and axotomized rat dorsal root ganglion neurons.
AB  - We compared the distribution of the alpha-subunit mRNAs of voltage-gated sodium
      channels Nav1.1-1.3 and Nav1.6-1.9 and a related channel, Nax, in histochemically
      identified neuronal subpopulations of the rat dorsal root ganglia (DRG). In the
      naive DRG, the expression of Nav1.1 and Nav1.6 was restricted to A-fiber neurons,
      and they were preferentially expressed by TrkC neurons, suggesting that
      proprioceptive neurons possess these channels. Nav1.7, -1.8, and -1.9 mRNAs were
      more abundant in C-fiber neurons compared with A-fiber ones. Nax was evenly
      expressed in both populations. Although Nav1.8 and -1.9 were preferentially
      expressed by TrkA neurons, other alpha-subunits were expressed independently of
      TrkA expression. Actually, all IB4(+) neurons expressed both Nav1.8 and -1.9, and
      relatively limited subpopulations of IB4(+) neurons (3% and 12%, respectively)
      expressed Nav1.1 and/or Nav1.6. These findings provide useful information in
      interpreting the electrophysiological characteristics of some neuronal
      subpopulations of naive DRG. After L5 spinal nerve ligation, Nav1.3 mRNA was up
      regulated mainly in A-fiber neurons in the ipsilateral L5 DRG. Although previous
      studies demonstrated that nerve growth factor (NGF) and glial cell-derived
      neurotrophic factor (GDNF) reversed this up-regulation, the Nav1.3 induction was
      independent of either TrkA or GFRalpha1 expression, suggesting that the induction
      of Nav1.3 may be one of the common responses of axotomized DRG neurons without a
      direct relationship to NGF/GDNF supply.

PMID- 18615541
TI  - Suggestive linkage on chromosome 2, 8, and 17 for lifetime major depression.
AB  - It is well established that major depressive disorder (MDD) is partly heritable.
      We present a genome-wide linkage study aiming to find regions on the genome that
      influence the vulnerability for MDD. Our sample consists of 110 Australian and 23
      Dutch pedigrees with two or more siblings affected with MDD (total N = 278).
      Linkage analysis was carried out in MERLIN. Three regions showed suggestive
      linkage signals. The highest LOD-score of 2.1 was found on chromosome 17 at 52.6
      cM along with LOD scores of 1.9 and 1.7 on chromosome 8 at 2.7 cM and chromosome
      2 at 90.6 cM, respectively. The result on chromosome 8 seems most promising as
      two previous studies also found linkage in this region, once suggestive and once
      significant. The linkage peak on chromosome 17 harbors the serotonin transporter
      gene. In the Australian and Dutch sample, the serotonin transporter length
      polymorphism did not show evidence for association, thus other genes in this
      region or other polymorphisms in the serotonin transporter gene might be
      associated with MDD. Further replication is needed to establish the relevance of
      our linkage finding on chromosome 2.

PMID- 18615543
TI  - Female social dynamics in a provisioned free-ranging band of the Sichuan snub
      nosed monkey (Rhinopithecus roxellana) in the Qinling Mountains, China.
AB  - Little information is available on the social dynamics of the Sichuan snub-nosed
      monkeys (Rhinopithecus roxellana). Here, we provide 5-year observational data on
      a provisioned free-ranging band in the Qinling Mountains, central China, from
      October 2001 to December 2005. The results of this study suggested that females
      place a high priority on maintaining long-term relationships with other female in
      their one-male units (OMUs). Females had more social interactions with unit
      members than with nonunit individuals. They showed relatively high rates of
      affiliation with their unit females, intermediate levels with the resident males,
      and low levels with individuals outside the unit. Females had few interactions
      with other resident males. Social interactions, especially affiliative
      interactions, were more symmetrical between focal females and their unit females
      than between focal females and the resident males. Thus female social
      interactions appeared to resemble those of other female-bonded primate societies.
      On the other hand, female transfers occurred sometimes. We recorded 11 cases of
      female immigration and 5 cases of female disappearance, 1 case of female
      intraband shift, and 2 cases of "merging of OMUs," which suggested that unit
      females might be loose-knit in this species. We discussed influencing factors on
      female Sichuan snub-nosed monkey social dynamics, by comparing them with those of
      Hamadryas and gelada baboons that also have multilevel societies.

PMID- 18615544
TI  - Maternal serum screening in cases of mosaic and translocation Down syndrome.
AB  - OBJECTIVES: To determine if the second-trimester maternal serum markers (MSM)
      screening for Down syndrome (DS) is efficient in DS mosaicism or structural
      rearrangement cases. METHOD: DS mosaic or translocation cases were reviewed from
      databases of routine MSM DS screening. The control group consisted of 977 trisomy
      21 cases included in a series of 854 902 patients (routine screening). DS risk
      was calculated by combination of maternal age and MSM [alpha-fetoprotein (AFP)
      and human choriogonadotrophin (hCG) or free beta-hCG and/or uE3] expressed in
      multiples of median (MoM). Mosaic DS cases were divided into three groups, < 10%,
      10-49%, and >or= 50% trisomy 21 cells. Translocation DS cases were divided into
      three groups, isochromosome, Robertsonian, or reciprocal translocation. Detection
      rate (DR) and MoMs were evaluated in each group. RESULTS: As many as 76 cases of
      nonstandard trisomy 21 were collected. For mosaic DS cases (n = 43) DR was 69.8%
      (not significantly different from the 70.8% of control group). When mosaicism was
      less than 10%, the DR dropped to 25%. For translocation DS cases (n = 33) DR was
      75.7% (not significantly different from control group) whatever the types of
      translocation. CONCLUSION: In the nonstandard DS cases, second-trimester MSMs
      gave the same detection rate as for standard trisomy 21, except the cases with
      low-level mosaicism (<10%).

PMID- 18615545
TI  - Prenatal diagnosis of a de novo partial trisomy 10p12.1-12.2 pter originating
      from an unbalanced translocation onto 15qter and confirmed with array CGH.

PMID- 18615546
TI  - Molecular prenatal diagnosis of Hb H hydrops fetalis caused by haemoglobin Adana
      and the implications to antenatal screening for alpha-thalassaemia.

PMID- 18615547
TI  - Second-trimester maternal serum free-beta-human chorionic gonadotropin and alpha
      fetoprotein levels in normal twin and singleton pregnancies: a report of local
      Chinese population.
AB  - OBJECTIVES: The study evaluated the differences between Chinese normal twin and
      singleton pregnancies in the levels of maternal serum free-beta-human chorionic
      gonadotropin (free beta-hCG) and alpha-fetoprotein (AFP) used in second-trimester
      Down syndrome (DS) screening. METHODS: The concentrations of maternal serum
      markers of 456 twin pregnancies and 12 067 singleton controls in gestational 15
      to 20 weeks were measured by time-resolved fluoroimmunoassay, and the levels of
      markers were compared between the twins and singletons. RESULTS: Significant
      differences were found between the levels of free beta-hCG in twins and twice of
      those in singletons in 16, 17 and 19 gestational weeks (p < 0.05 for all); while
      considering AFP, significant differences were found in 16 and 19 gestational
      weeks (p < 0.05 for both). No correlations were found in twins between the levels
      of markers and maternal weights in most gestational weeks (Free beta-hCG: p >
      0.05 for 15 to 18 and 20 gestational weeks; AFP: p > 0.05 for 16 to 20
      gestational weeks). CONCLUSIONS: The Chinese gestational age-specific levels of
      maternal serum markers in normal twins are not twice as those in singletons. The
      current weight-correction model for DS screening may be not feasible for twins.

PMID- 18615549
TI  - Camouflaged sampling and contacting of people from administrative databases:
      reaching target patients without knowing who they are.
AB  - BACKGROUND: Methods are needed for using confidential data to select and reach
      patients without compromising their health privacy. METHODS: (a) SAMPLING: we
      created (1) an anonymous list of encrypted personal health numbers (EPHNs) of
      target patients (e.g., users of the medications of interest) and (2) an anonymous
      list of EPHNs of people randomly sampled from the general population of non
      users. The two lists were merged and randomly ordered to make a camouflaged list.
      People on the second list were called camouflagers. Then EPHNs were matched to
      names and contact information, and the EPHNs were removed from the contact list.
      (b) Contacting: when we contacted patients by mail or telephone, we told them
      their names were selected from one of two lists, and their health status was
      unknown to us. We invited respondents to answer (1) a short survey for the
      general population or (2) a longer survey concerning the target condition.
      RESULTS: In five studies, the percentage of camouflagers--equal to one minus the
      positive predictive value of the camouflaged list--has varied from 10 to over
      50%. This depended on the psychosocial sensitivity of the target medications or
      health conditions, the natural camouflaging by the population's heterogeneity or
      inaccuracy of the data on the target characteristic, the degree of stratification
      of the sample, and the cost of contacting. CONCLUSION: Camouflaging enables
      administrative data to be used for contacting target patients in selected
      populations while adhering to current data privacy laws and ethics principles.

PMID- 18615550
TI  - The availability and usage frequency of real time ultrasound by physiotherapists
      in South Australia: an observational study.
AB  - BACKGROUND AND PURPOSE: Real time ultrasound (RTUS) is an emerging imaging
      modality in physiotherapy. Anecdotal evidence suggests that it is being used as
      an assessment and biofeedback tool for various deep core stabilizing muscles.
      However, how and why physiotherapists use RTUS in the clinical setting has not
      yet been reported. Therefore, this study aimed to establish the availability and
      usage frequency of RTUS by physiotherapists in South Australia. In addition, the
      study aimed to describe how physiotherapists were using RTUS and how they were
      educated in its use. METHOD: A questionnaire was developed and mailed to all
      physiotherapists registered with the Physiotherapy Board of South Australia (n =
      1328) between February and March 2007. RESULTS: A response rate of 50% was
      achieved with 664 completed usable questionnaires returned. At the current time,
      only a small proportion of respondents used RTUS (11.6%), while slightly more had
      access to a machine (19.4%). RTUS was used most commonly for assessment (88.3%)
      and biofeedback (87.0%) of the abdominal (94.7%), pelvic floor (72.7%) and
      multifidus (54.5%) muscles. Of all respondents, 26.7% had trained in its use with
      most completing two hours or less of training. CONCLUSIONS: This is the first
      published study to describe how and why physiotherapists are using RTUS in
      clinical practice. RTUS appears to be a relatively uncommon modality potentially
      limited by insufficient access to equipment and educational opportunities. The
      findings highlight a greater need for education and training in the use of RTUS
      for physiotherapy practice.

PMID- 18615551
TI  - Philadelphia-negative acute myeloid leukemia with new chromosomal abnormalities
      developing after first-line imatinib treatment for chronic phase chronic myeloid
      leukemia.

PMID- 18615552
TI  - Pure red-cell aplasia associated with pegylated interferon-alpha-2b plus
      ribavirin.

PMID- 18615553
TI  - Elevated serum ferritin in patients with a myelodysplastic syndrome: how much of
      a problem?

PMID- 18615555
TI  - Induction of integrin beta1 expression in bone marrow cells after chemotherapy
      correlates with the overexpression of lung resistance protein and poor outcome in
      patients with multiple myeloma.

PMID- 18615554
TI  - Successful use of the anti-CD25 antibody daclizumab in an adult patient with
      hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe inflammatory
      disorder marked by abnormal cytotoxic T and natural killer cell activity,
      resulting in impaired clearance of pathogen, excessive cytokine production, and
      continued immune system activation. Soluble IL-2 receptor (sIL-2R or sCD25) is
      typically elevated in HLH and can serve as a marker of disease activity, although
      its role in the pathophysiology of the disease is unclear. Here we present a case
      of an adult patient with steroid-dependent HLH who was treated successfully with
      daclizumab, a monoclonal anti-CD25 antibody, allowing successful withdrawal of
      steroid therapy without an increase in symptoms.

PMID- 18615556
TI  - Hydroxyurea therapy lowers circulating DNA levels in sickle cell anemia.
AB  - Hydroxyurea reduces the frequency of acute pain in sickle cell disease (SCD). We
      sought to determine if hydroxyurea therapy affects cell free DNA (cfDNA) levels
      in SCD. cfDNA levels fell in all 10 patients studied; before hydroxyurea, mean
      was 1,879 (95% CI 1,104-3,199) GE/mL; after hydroxyurea, mean was 780 (95% CI,
      634-959) GE/mL (P = 0.002). Mean cfDNA level in the 10 HbSS adults prior to
      starting hydroxyurea was also significantly higher than that in 115 HbSS case
      controls who had never taken hydroxyurea (1,879 vs 975 GE/mL, P = 0.02). cfDNA
      levels may be useful in monitoring response to hydroxyurea therapy in SCD.

PMID- 18615558
TI  - Factors affecting fecal glucocorticoid levels in semi-free-ranging female
      mandrills (Mandrillus sphinx).
AB  - Subordinate female cercopithecine primates often experience decreased
      reproductive success in comparison with high-ranking females, with a later age at
      sexual maturity and first reproduction and/or longer interbirth intervals. One
      explanation that has traditionally been advanced to explain this is high levels
      of chronic social stress in subordinates, resulting from agonistic and aggressive
      interactions and leading to higher basal levels of glucocorticoids. We assessed
      the relationships among fecal cortisol levels and reproductive condition,
      dominance rank, degree of social support, and fertility in female mandrills
      (Mandrillus sphinx) living in a semi-free-ranging colony in Franceville, Gabon.
      Lower-ranking females in this colony have a reproductive disadvantage relative to
      higher-ranking females, and we were interested in determining whether this
      relationship between dominance rank and reproductive success is mediated through
      stress hormones. We analyzed 340 fecal samples from 19 females, collected over a
      14-month period. We found that pregnant females experienced higher fecal cortisol
      levels than cycling or lactating females. This is similar to results for other
      primate species and is likely owing to increased metabolic demands and
      interactions between the hypothalamus-pituitary-adrenal axis, estrogen, and
      placental production of corticotrophin releasing hormones during pregnancy. There
      was no influence of dominance rank on fecal cortisol levels, suggesting that
      subordinate females do not suffer chronic stress. This may be because female
      mandrills have a stable social hierarchy, with low levels of aggression and high
      social support. However, we found no relationship between matriline size, as a
      measure of social support, and fecal cortisol levels. Subordinates may be able to
      avoid aggression from dominants in the large enclosure or may react only
      transiently to specific aggressive events, rather than continuously expecting
      them. Finally, we found no relationship between fecal cortisol levels and
      fertility. There was no difference in fecal cortisol levels between conceptive
      and nonconceptive cycles, and no significant relationship between fecal cortisol
      level and either the length of postpartum amenorrhea or the number of cycles
      before conception. This suggests that the influence of dominance rank on female
      reproductive success in this population is not mediated through chronic stress in
      subordinate females, and that alternative explanations of the relationship
      between social rank and reproduction should be sought.

PMID- 18615557
TI  - Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal
      functions.
AB  - Cell-cell interactions through adhesion molecules play key roles in the
      development of the nervous system. Synaptic cell adhesion molecules (SynCAMs)
      comprise a group of four immunoglobulin (Ig) superfamily members that mediate
      adhesion and are prominently expressed in the brain. Although SynCAMs have been
      implicated in the differentiation of neurons, there has been no comprehensive
      analysis of their expression patterns. Here we examine the spatiotemporal
      expression patterns of SynCAMs by using reverse transcriptase-polymerase chain
      reaction, in situ hybridization, and immunohistological techniques. SynCAMs 1-4
      are widely expressed throughout the developing and adult central nervous system.
      They are prominently expressed in neurons throughout the brain and are present in
      both excitatory and inhibitory neurons. Investigation of different brain regions
      in the developing and mature mouse brain indicates that each SynCAM exhibits a
      distinct spatiotemporal expression pattern. This is observed in all regions
      analyzed and is particularly notable in the cerebellum, where SynCAMs display
      highly distinct expression in cerebellar granule and Purkinje cells. These unique
      expression profiles are complemented by specific heterophilic adhesion patterns
      of SynCAM family members, as shown by cell overlay experiments. Three prominent
      interactions are observed, mediated by the extracellular domains of SynCAMs 1/2,
      2/4, and 3/4. These expression and adhesion profiles of SynCAMs together with
      their previously reported functions in synapse organization indicate that SynCAM
      proteins contribute importantly to the synaptic circuitry of the central nervous
      system.

PMID- 18615561
TI  - Dental crown size and sex hormone concentrations: another look at the development
      of sexual dimorphism.
AB  - Previous researchers hypothesized that tooth types forming during early childhood
      should be less sexually dimorphic than those forming during later childhood, if
      sex hormone concentration differences between males and females increase
      progressively throughout childhood and can affect tooth size. Descriptive tooth
      size data have recently been cited in support of this hypothesis, particularly
      with respect to differences in sexual dimorphism among the tooth types of tooth
      classes. The present study tests this hypothesis for the mesiodistal dimension of
      human permanent teeth using published data for incisor, premolar, and molar tooth
      classes from seven diverse populations. The sample size for each tooth type per
      population was at least 50. This study also tests a modification of this
      hypothesis which takes into account the postnatal testosterone surge in males and
      the low levels of sex hormones in both sexes prior to puberty. Predictions are
      developed for both the original and modified hypotheses. The "D" statistic, the
      total area of nonoverlap between the phenotypic distributions of males and
      females, is used to quantify sexual dimorphism. Comparison of D values for
      different tooth types within tooth classes across these seven populations does
      not strongly support either hypothesis. These results suggest that gross changes
      in sex hormone concentrations during development are not related to population
      wide patterns of sexual dimorphism among the tooth types of human permanent tooth
      classes, as recent studies indicate. This finding is consistent with other
      studies which suggest that sex hormones have only a minor role in generating
      crown size sexual dimorphism.

PMID- 18615559
TI  - Anatomical and neurochemical characterization of dopaminergic interplexiform
      processes in mouse and rat retinas.
AB  - Dopaminergic (DA) neurons of mouse and rat retinas are of the interplexiform
      subtype (DA-IPC), i.e., they send processes distally toward the outer retina,
      exhibiting numerous varicosities along their course. The primary question we
      addressed was whether distally located DA-IPC varicosities, identified by
      tyrosine hydroxylase (TH) immunoreactivity, had the characteristic presynaptic
      proteins associated with calcium-dependent vesicular release of neurotransmitter.
      We found that TH immunoreactive varicosities in the outer retina possessed
      vesicular monoamine transporter 2 and vesicular GABA transporter, but they lacked
      immunostaining for any of nine subtypes of voltage-dependent calcium channel.
      Immunoreactivity for other channels that may permit calcium influx such as
      certain ionotropic glutamate receptors and canonical transient receptor potential
      channels (TRPCs) was similarly absent, although DA-IPC varicosities did show
      ryanodine receptor immunoreactivity, indicating the presence of intracellular
      calcium stores. The synaptic vesicle proteins sv2a and sv2b and certain other
      proteins associated with the presynaptic membrane were absent from DA-IPC
      varicosities, but the vesicular SNARE protein, vamp2, was present in a fraction
      of those varicosities. We identified a presumed second class of IPC that is
      GABAergic but not dopaminergic. Outer retinal varicosities of this putative
      GABAergic IPC did colocalize synaptic vesicle protein 2a, suggesting they
      possessed a conventional vesicular release mechanism.

PMID- 18615560
TI  - Regional and cellular localization of the CXCl12/SDF-1 chemokine receptor CXCR7
      in the developing and adult rat brain.
AB  - The chemokine stromal cell-derived factor-1 (SDF-1) regulates neuronal
      development via the chemokine receptor CXCR4. In the adult brain the SDF-1/CXCR4
      system was implicated in neurogenesis, neuromodulation, brain inflammation, tumor
      growth, and HIV encephalopathy. Until the recent identification of RDC1/CXCR7 as
      the second SDF-1 receptor, CXCR4 was considered to be the only receptor for SDF
      1. Here we provide the first map of CXCR7 mRNA expression in the embryonic and
      adult rat brain. At embryonic stages, CXCR7 and CXCR4 were codistributed in the
      germinative zone of the ganglionic eminences, caudate putamen, and along the
      routes of GABAergic precursors migrating toward the cortex. In the cortex, CXCR7
      was identified in GABAergic precursors and in some reelin-expressing Cajal
      Retzius cells. Unlike CXCR4, CXCR7 was abundant in neurons forming the cortical
      plate and sparse in the developing dentate gyrus and cerebellar external germinal
      layer. In the adult brain, CXCR7 was expressed by blood vessels, pyramidal cells
      in CA3, and mature dentate gyrus granule cells, which is reminiscent of the SDF-1
      pattern. CXCR7 and CXCR4 overlapped in the wall of the four ventricles. Further
      neuronal structures expressing CXCR7 comprised the olfactory bulb, accumbens
      shell, supraoptic and ventromedial hypothalamic nuclei, medial thalamus, and
      brain stem motor nuclei. Also, GLAST-expressing astrocytes showed signals for
      CXCR7. Thus, CXCR4 and CXCR7 may cooperate or act independently in SDF-1
      dependent neuronal development. In mature neurons and blood vessels CXCR7 appears
      to be the preponderant SDF-1-receptor.

PMID- 18615562
TI  - Cryo-X-ray analysis-A novel tool to better understand the physicochemical
      reactions at the bioglass/biological fluid interface.
AB  - The present study deals with the short-term physicochemical reactions at the
      interface between bioactive glass particles [55SiO(2)-20CaO-9P(2)O(5)-12Na(2)O
      4MgO. mol%] and biological fluid (Dulbecco Modified Eagle's Medium (DMEM)). The
      physicochemical reactions within the interface are characterized by scanning
      transmission electron microscopy (TEM) (STEM) associated with Energy-dispersive X
      ray spectroscopy (EDXS). Microanalysis of diffusible ions such as sodium,
      potassium, or oxygen requires a special care. In the present investigation the
      cryo-technique was adopted as a suitable tool for the specimen preparation and
      characterization. Cryosectioning is essential for preserving the native
      distribution of ions so that meaningful information about the local
      concentrations can be obtained by elemental microanalysis. The bioglass particles
      immersed in biological fluid for 24 h revealed five reaction stages: (i)
      dealkalization of the surface by cationic exchange (Na(+), Ca(2+) with H(+) or
      H(3)O(+)); (ii) loss of soluble silica in the form of Si(OH)(4) to the solution
      resulting from the breakdown of Si--O--Si bonds (iii); repolymerization of
      Si(OH)(4) leading to condensation of SiO(2)); (iv) migration of Ca(2+) and PO(4)
      (3-) to the surface through the SiO(2)-rich layer to form CaO-P(2)O(5) film; (v)
      crystallization of the amorphous CaO-P(2)O(5) by incorporating OH-- or CO(3) (2-)
      anions with the formation of three different surface layers on the bioactive
      glass periphery. The thickness of each layer is approximately 300 nm and from the
      inner part to the periphery they consist of Si--OH, which permits the diffusion
      of Ca(2+) and PO(4) (3-) ions and the formation of the middle Ca--P layer, and
      finally the outer layer composed of Na--O, which acts as an ion exchange layer
      between Na(+) ions and H(+) or H(3)O(+) from the solution.

PMID- 18615563
TI  - Chitosan/poly(L-lactic acid) multilayered membrane for guided tissue
      regeneration.
AB  - A chitosan/poly(L-lactic acid) (PLLA) multilayered membrane was prepared for the
      purpose of guided tissue regeneration (GTR). The membrane was composed of the
      outer layers of chitosan mesh and the middle layer of nanoporous PLLA membrane.
      The outer membranes of chitosan fibrous mesh present a highly biocompatible and
      rough surface for ease of cell adherence. The PLLA membrane is intended to
      provide mechanical strength to the membrane, thereby preventing epithelial
      invasion. The PLLA membrane was applied as a local drug delivery carrier for
      growth factors. Regular pores in PLLA membrane were generated through phase
      inversion of polymer solution. The membrane retained its integrity during the
      degradation process in vitro (for up to 8 weeks), which is a requirement for
      providing enough space in vivo in the GTR procedure. Osteoblasts firmly attached
      to broad cytoplasmic extensions along with the microfibers of the membrane. The
      phenotypic expression of cultured osteoblasts on the membrane was measured by a
      reverse transcriptase-polymerase chain reaction. New bone had formed beneath the
      chitosan/PLLA membrane. These results suggested that the chitosan/PLLA membranes
      properly functioned as biocompatible and mechanically stable barriers for GTR.

PMID- 18615564
TI  - Mitotic catastrophe and apoptosis induced by docetaxel in hormone-refractory
      prostate cancer cells.
AB  - Studies performed in different experimental and clinical settings have shown that
      Docetaxel (Doc) is effective in a wide range of tumors and that it exerts its
      activity through multiple mechanisms of action. However, the sequence of events
      induced by Doc which leads to cell death is still not fully understood. Moreover,
      it is not completely clear how Doc induces mitotic catastrophe and whether this
      process is an end event or followed by apoptosis or necrosis. We investigated the
      mechanisms by which Doc triggers cell death in hormone-refractory prostate cancer
      cells by analyzing cell cycle perturbations, apoptosis-related marker expression,
      and morphologic cell alterations. Doc induced a transient increase in G2/M phase
      followed by the appearance of G0/1 hypo- and hyperdiploid cells and increased p21
      expression. Time- and concentration-dependent apoptosis was induced in up to 70%
      of cells, in concomitance with Bcl-2 phosphorylation, which was followed by
      caspase-2 and -3 activation. In conclusion, Doc would seem to trigger apoptosis
      in hormone-refractory prostate cancer cells via mitotic catastrophe through two
      forms of mitotic exit, in concomitance with increased p21 expression and caspase
      2 activation.

PMID- 18615565
TI  - Assessing mandibular shape variation within Gigantopithecus using a geometric
      morphometric approach.
AB  - This study provides a survey of mandibular shape in a sample of extant hominoids
      (Pan, Gorilla, Pongo, and Hylobates), as well as extinct Asian and Eurasian taxa
      (Ouranopithecus, Sivapithecus, and Gigantopithecus) in order to compare overall
      shape similarity. Results presented call into question differences in mandible
      shape recently used to distinguish Gigantopithecus giganteus from Gigantopithecus
      blacki and to justify resurrecting a different generic designation,
      "Indopithecus," for the former. It is concluded that while the two large-bodied
      Asian taxa may have been adapted to slightly different dietary niches with
      different geographic and temporal ranges, the unique mandibular/dental characters
      that the two taxa share should not be viewed as independent evolutionary
      developments.

PMID- 18615566
TI  - Confocal imaging and tracking of the exocytotic routes for D-serine-mediated
      gliotransmission.
AB  - D-Serine is an astrocyte-derived regulator for N-methyl-D-aspartate receptors,
      but the intracellular routes of its trafficking are still largely unknown. Here,
      we combined confocal microscopy with colocalization quantification to track the
      astrocytic organelles that store D-serine. We report that D-serine colocalizes
      with the transfected eGFP-synaptobrevin/VAMP2 and eGFP-cellubrevin/VAMP3, two v
      SNAREs of the regulated secretory pathway. No significant colocalization was
      found with markers of the endosomal sorting and recycling system: EEA1, eGFP
      endobrevin/VAMP8, eGFP-TI-VAMP/VAMP7, LAMP1, and CD63. Blockade of vesicular
      budding with colchicine shows that secretory vesicles import D-serine downstream
      to the Golgi apparatus. Finally, treatment of astrocytes with the Ca2+-ionophore
      A23187, glutamate agonists, or bradykinin trigger translocation of
      synaptobrevin/VAMP2 to the plasma membrane with a concomitant disappearance of D
      serine from the regulated secretory pathway. Our results provide morphological
      evidence for a vesicular storage of D-serine in the regulated secretory pathway
      and the possible recruitment of these stores by Ca2+ mobilization to release D
      serine.

PMID- 18615567
TI  - Comparative gene expression profiling of olfactory ensheathing glia and Schwann
      cells indicates distinct tissue repair characteristics of olfactory ensheathing
      glia.
AB  - Olfactory ensheathing glia (OEG) are a specialized type of glia that support the
      growth of primary olfactory axons from the neuroepithelium in the nasal cavity to
      the brain. Transplantation of OEG in the injured spinal cord promotes sprouting
      of injured axons and results in reduced cavity formation, enhanced axonal and
      tissue sparing, remyelination, and angiogenesis. Gene expression analysis may
      help to identify the molecular mechanisms underlying the ability of OEG to
      recreate an environment that supports regeneration in the central nervous system.
      Here, we compared the transcriptome of cultured OEG (cOEG) with the
      transcriptomes of cultured Schwann cells (cSCs) and of OEG directly obtained from
      their natural environment (nOEG), the olfactory nerve layer of adult rats.
      Functional data mining by Gene Ontology (GO)-analysis revealed a number of
      overrepresented GO-classes associated with tissue repair. These classes include
      "response to wounding," "blood vessel development," "cell adhesion," and GO
      classes related to the extracellular matrix and were overrepresented in the set
      of differentially expressed genes between both comparisons. The current screening
      approach combined with GO-analysis has identified distinct molecular properties
      of OEG that may underlie their efficacy and interaction with host tissue after
      implantation in the injured spinal cord. These observations can form the basis
      for studies on the function of novel target molecules for therapeutic
      intervention after neurotrauma.

PMID- 18615568
TI  - Glial TLR4 receptor as new target to treat neuropathic pain: efficacy of a new
      receptor antagonist in a model of peripheral nerve injury in mice.
AB  - Neuropathic pain remains a prevalent clinical problem because it is often poorly
      responsive to the currently used analgesics, thus it is crucial the
      identification of new potential targets and drugs. Recent evidence indicated that
      microglial cells in the spinal cord are critically involved in the development
      and maintenance of neuropathic pain, with a pivotal role of toll-like receptor 4
      (TLR4). Binding of an endogenous ligand to TLR4 might be considered an important
      step in the regulation of microglia activity in pain facilitation, suggesting
      that a mechanism aimed to inhibit such a binding could be effective against
      neuropathic pain. We have synthesized new ligands to TLR4 with antagonistic
      activity. In the present work we evaluated the efficacy of the most potent TLR4
      antagonist synthesized by us (FP-1), administered in mice with painful
      neuropathy. The repeated treatment of neuropathic mice with FP-1 (5-10 mg/kg,
      i.p.) evoked a relief of both thermal hyperalgesia and mechanical allodynia,
      whereas the administration of the highest dose to TLR4 knockout neuropathic mice
      revealed that in the absence of TLR4 receptor, the compound lost its efficacy. As
      consequence of TLR4 binding, the repeated treatment with FP-1 prevented the
      activation of the transcription factor NF-kB and the TNFalpha overproduction in
      the spinal cord. Together, our findings support the previous evidence indicative
      for a contribution of glial TLR4 to the initiation of neuropathic pain, suggest
      it as potential innovative target to treat this debilitating disease, and propose
      FP-1 as lead compound for the development of new effective drugs.

PMID- 18615569
TI  - GLT-1 expression and Glu uptake in rat cerebral cortex are increased by
      phencyclidine.
AB  - Using western blottings, microdialysis, and functional assays we tested the
      hypothesis that phencyclidine (PCP) modifies the expression and function of
      glutamate (Glu) transporters in the rat frontal cortex. Western blotting studies
      revealed that administration of PCP (10 mg/kg/day; 7 days) increased
      significantly the expression of the astrocytic Glu transporter GLT-1/EAAT2.
      Functional studies showed that PCP increased significantly Na+-dependent Glu
      uptake in slices and in neuron/astrocyte co-cultures, and microdialysis studies
      evidenced that PCP treatment reduced basal Glu output. In our experimental
      conditions, PCP did not induce toxicity. These studies show that PCP increases
      the expression of GLT-1 in the cerebral cortex, thereby increasing Glu uptake and
      reducing extracellular [Glu].

PMID- 18615570
TI  - Precis of 'an abductive theory of scientific method'.
AB  - This short article is a precis of the author's (2005a) abductive theory of
      scientific method. This theory of method assembles a complex of specific
      strategies and methods of relevance to psychology that are employed in the
      detection of empirical phenomena and the subsequent construction of explanatory
      theories. A characterization of the nature of phenomena is given, and the process
      of their detection is briefly described in terms of a multistage model of data
      analysis. The construction of explanatory theories is shown to involve their
      generation through abductive, or explanatory, reasoning, their development
      through analogical modeling, and their fuller appraisal in terms of judgments of
      the best of competing explanations. The nature and limits of this theory of
      method are discussed in the light of relevant developments in scientific
      methodology.

PMID- 18615571
TI  - Obituary: Daris R. Swindler (1925-2007).

PMID- 18615572
TI  - Brief Communication: Latent toxoplasmosis and salivary testosterone concentration
      -important confounding factors in second to fourth digit ratio studies.
AB  - A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D
      ratio), has been shown to reflect the prenatal concentration of sex steroid
      hormones and to correlate with many personality, physiological, and life history
      traits. The correlations are usually stronger for the right than the left hand.
      Most studies have shown that the 2D:4D ratio does not vary with age or postnatal
      concentration of sex steroid hormones. Recently, a strong association between
      left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has
      been reported. We hypothesized that the confounding effect of Toxoplasma
      infection on left hand 2D:4D ratio could be responsible for the stronger
      association between different traits and right hand rather than left hand 2D:4D
      ratio. This confounding effect of toxoplasmosis could also be responsible for the
      difficulty in finding an association between 2D:4D ratio and age or postnatal
      steroid hormone concentration. To test this hypothesis, we analyzed the
      association between sex and age and 2D:4D ratio in a population of 194 female and
      106 male students with and without controlling for the confounding variables of
      Toxoplasma infection and testosterone concentration. Our results showed that the
      relationship between age and sex and 2D:4D ratio increased sharply when
      Toxoplasma infection and testosterone concentration were controlled. These
      results suggest that left hand 2D:4D ratio is more susceptible to postnatal
      influences and that the confounding factors of Toxoplasma infection, testosterone
      concentration and possibly also age, should be controlled in future 2D:4D ratio
      studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than
      Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right
      hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high
      prevalence of Toxoplasma infection than in those with a low prevalence.

PMID- 18615573
TI  - Isotopic and dental evidence for infant and young child feeding practices in an
      imperial Roman skeletal sample.
AB  - This study integrates isotopic, palaeopathological, and historical evidence to
      investigate infant and young child feeding practices in a Roman period (1st to
      3rd centuries AD) skeletal sample from the Isola Sacra necropolis (Rome, Italy).
      Stable isotope analysis of bone collagen from 37 rib samples indicates that
      transitional feeding began by the end of the first year and weaning occurred by 2
      2.5 years of age. Both delta(15)N and delta(13)C data clearly show the trophic
      level effect associated with breastfeeding. Childhood diet is investigated using
      dental pathology data in the deciduous dentitions of 78 individuals aged between
      1 and 12 years. The presence of calculus, caries, and tooth wear in young
      children suggests that individuals were provided complementary foods and other
      items that impacted their dental health at an early age. The isotopic and dental
      data are generally consistent with the historical evidence from the Roman period
      with respect to the general timetable of weaning and the character of
      complementary foods. This is the first study to integrate isotopic and deciduous
      dental pathology data to explore infant and young child feeding practices in the
      Roman world.

PMID- 18615574
TI  - Craniometric variation of the Ainu: an assessment of differential gene flow from
      northeast Asia into northern Japan, Hokkaido.
AB  - In and after the latest Neolithic period in Japan (approximately B.P. 2,300
      years), there were two distinct waves of migration from eastern Asia. One is well
      known as successive episodes in which indigenous inhabitants of main-island Japan
      were intruded on by new arrivals with advanced technology, and of a different
      genetic stock. Another migration of people and culture, identified as the Okhotsk
      culture, reached the northeastern part of Hokkaido. As opposed to main-island
      Japan, the morphological continuity from the Neolithic to recent inhabitants in
      Hokkaido (Ainu) is notable, so that the evidence of admixture easily could have
      escaped notice. In this study, the effects of gene flow from an outside source on
      the pattern of among-group variation of Hokkaido Ainu are examined by means of
      two models. One is the R-matrix model comparing observed and expected
      craniometric variation for estimating differential external gene flow into a
      region. The other is a simple simulation model that estimates admixture in a
      population with two parental populations. The two approaches give similar
      results. The results suggest the possibility of admixture between the migrants
      from Northeast Asia, the Okhotsk culture people, and the indigenous inhabitants
      in Hokkaido during the 5th to 12th centuries A.D., at least in northeastern
      Hokkaido. Such gene flow may have a certain degree of effect on the genetic
      structure of recent Ainu. The findings further suggest morphological
      heterogeneity in Northeast Asia during the Holocene that has relevance for
      understanding the morphological heterogeneity seen through time in the New World.

PMID- 18615575
TI  - What is it going to be? Pattern and potential function of natal coat change in
      sexually dichromatic redfronted lemurs (Eulemur fulvus rufus).
AB  - In some primate species, pelage colorations at birth contrast with adult
      colorations. The intensity of natal coats and their phylogenetic distribution is
      highly variable within primates. Natal coat coloration seems to change to adult
      coloration in most species when infants become independent from their mothers,
      but an accepted functional explanation for natal coats is not available. Here we
      describe pelage coloration change in sexually dichromatic redfronted lemurs
      (Eulemur fulvus rufus) in Kirindy Forest, and propose a new functional hypothesis
      for this phenomenon. In this species, infants are born with adult male coloration
      and female infants subsequently undergo a change in coloration. Using digital
      pictures and behavioral data collected on eight mother-offspring dyads from birth
      until the end of the coloration change, we 1) described timing and pattern of
      pelage developmentin redfronted lemur infants and 2) examined behavioral
      developmental correlates of the coloration change. The color change took place
      between 7 and 17 weeks of age and coincided with advanced physical independence;
      a pattern also found in monochromatic primate species with natal coats. No
      behavioral differences between male and female infants were found. Hypotheses
      about the ultimate function of natal coats focusing on enhanced infant care or
      reduced infanticide risk did not explain the pelage change in redfronted lemurs.
      The natal pelage pattern in this species may instead serve as sexual mimicry.
      Accordingly, female infants may mimic males during the most vulnerable
      developmental phase to avoid sex-specific aggression by adult females in a
      species with intense female-female aggression and competition.

PMID- 18615576
TI  - Brief communication: Skeletal biology past and present: Are we moving in the
      right direction?
AB  - In 1982, Spencer's edited volume A History of American Physical Anthropology:
      1930-1980 allowed numerous authors to document the state of our science,
      including a critical examination of skeletal biology. Some authors argued that
      the first 50 years of skeletal biology were characterized by the descriptive
      historical approach with little regard for processual problems and that
      technological and statistical analyses were not rooted in theory. In an effort to
      determine whether Spencer's landmark volume impacted the field of skeletal
      biology, a content analysis was carried out for the American Journal of Physical
      Anthropology from 1980 to 2004. The percentage of skeletal biology articles is
      similar to that of previous decades. Analytical articles averaged only 32% and
      are defined by three criteria: statistical analysis, hypothesis testing, and
      broader explanatory context. However, when these criteria were scored
      individually, nearly 80% of papers attempted a broader theoretical explanation,
      44% tested hypotheses, and 67% used advanced statistics, suggesting that the
      skeletal biology papers in the journal have an analytical emphasis. Considerable
      fluctuation exists between subfields; trends toward a more analytical approach
      are witnessed in the subfields of age/sex/stature/demography, skeletal
      maturation, anatomy, and nonhuman primate studies, which also increased in
      frequency, while paleontology and pathology were largely descriptive. Comparisons
      to the International Journal of Osteoarchaeology indicate that there are
      statistically significant differences between the two journals in terms of
      analytical criteria. These data indicate a positive shift in theoretical
      thinking, i.e., an attempt by most to explain processes rather than present a
      simple description of events.

PMID- 18615578
TI  - Pregabalin and gabapentin inhibit substance P-induced NF-kappaB activation in
      neuroblastoma and glioma cells.
AB  - Pregabalin and gabapentin are lipophilic amino acid derivatives of gamma-amino
      butyric acid that show anticonvulsant and analgesic activity against neuropathic
      pain. In this study, we investigated their actions on substance P-induced NF
      kappaB activation in human neuroblastoma and rat glioma cells. Pregabalin and
      gabapentin decreased substance P-induced NF-kappaB activation in these cells.
      These drugs also inhibited NF-kappaB activation in rat spinal dorsal root ganglia
      cells pre-treated in vitro with substance P. These results suggest a previously
      undefined role of pregabalin and gabapentin in the regulation of inflammation
      related intracellular signaling in both neuronal and glial cells.

PMID- 18615577
TI  - Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell
      polarization and enhanced motility.
AB  - Focal adhesion kinase (FAK) plays key roles in cell adhesion and migration. We
      now report that the delayed rectifier Kv2.1 potassium channel, through its LD
      like motif in N-terminus, may interact with FAK and enhance phosphorylation of
      FAK(397) and FAK(576/577). Overlapping distribution of Kv2.1 and FAK was observed
      on soma and proximal dendrites of cortical neurons. FAK expression promotes a
      polarized membrane distribution of the Kv2.1 channel. In Kv2.1-transfected CHO
      cells, formation of the Kv2.1-FAK complex was stimulated by fibronectin/integrin
      and inhibited by the K(+) channel blocker tetraethylammonium (TEA). FAK
      phosphorylation was minimized by shRNA knockdown of the Kv2.1 channel, point
      mutations of the N-terminus, and TEA, respectively. Cell migration morphology was
      altered by Kv2.1 knockdown or TEA, hindering cell migration activity. In wound
      healing tests in vitro and a traumatic injury animal model, Kv2.1 expression and
      co-localization of Kv2.1 and FAK significantly enhanced directional cell
      migration and wound closure. It is suggested that the Kv2.1 channel may function
      as a promoting signal for FAK activation and cell motility.

PMID- 18615579
TI  - The mesenchymal stromal cell contribution to homeostasis.
AB  - Adult mesenchymal stromal cells (MSCs) are undifferentiated multi-potent cells
      predominantly residing in the bone marrow (BM), but also present with similar but
      not identical features in many other tissues such as blood, placenta, dental
      pulp, and adipose tissue. MSCs have the potential to differentiate into multiple
      skeletal phenotypes like osteoblasts, chondrocytes, adipocytes, stromal cells,
      fibroblasts, and possibly tendons. MSCs differentiation potential, ex vivo
      expansion capacity, nurturing and immunomodulatory proficiencies oriented these
      versatile cells in several areas of ongoing clinical applications. However, the
      absence of MSC-specific markers for isolation and characterization together with
      the lack of a comprehensive view of the molecular pathways governing their
      particular biological properties, remains a primary obstacle to their research
      and application. In this review we discuss some areas of growing interest in MSCs
      biology: their contribution to the hematopoietic stem cell (HSC) niche, to
      regenerative medicine, their role in cancer and in therapy as delivery tools and
      their micro-RNA (miRNA) signatures. Despite rapid progress in the MSC field, it
      is generally thought that only a fraction of their full potential has been
      realized thus far.

PMID- 18615580
TI  - 15-deoxy-delta 12,14-prostaglandin J(2) inhibits the synthesis of the acute phase
      protein SIP24 in cartilage: Involvement of COX-2 in resolution of inflammation.
AB  - We previously demonstrated that, in the MC615 cartilage cell line, the p38/NF-kB
      pathway is activated both during differentiation and in response to an
      inflammatory stimulus. In both cases, the p38/NF-kB pathway activation leads to
      the expression of the lipocalin SIP24 and of COX-2. Given the fact that, in the
      same cells, the COX-2 expression is sustained during the inflammation resolution,
      at the same time that the SIP24 expression is suppressed, in the present study we
      tested the hypothesis that COX-2 products play a role in SIP24 repression. Taken
      together, our results suggest that, during the resolution of inflammation, COX-2
      represses the acute phase protein SIP24 and restores physiological conditions,
      possibly through a pathway involving PPARgamma. Experimental evidences being the
      following: (1) 15-deoxy-delta 12,14-prostaglandin J(2), but not PGE(2): (i)
      inhibits the expression of SIP24 in the inflammatory phase and induces COX-2
      synthesis; (ii) represses NF-kB activation induced by LPS; (iii) represses the
      synthesis of microsomal PGE Synthase-1 induced by LPS. (2) PPARgamma and
      PPARalpha are present in MC615 cells in both proliferating and hyperconfluent
      cultures. (3) PPARgamma ligand GW7845, but not PPARalpha ligand GW7647: (i)
      represses the expression of SIP24 induced by LPS; (ii) induces COX-2 expression.
      (4) p38 is involved in the PPARgamma mediated induction of COX-2. In fact 15
      deoxy-delta 12,14-prostaglandin J(2) activates p38 and the cell pretreatment with
      the p38 specific inhibitor SB203580 represses the expression of COX-2 induced by
      both the 15-deoxy-delta12,14-prostaglandin J(2) and the PPARgamma ligand GW7845.

PMID- 18615581
TI  - Low-power laser irradiation activates Src tyrosine kinase through reactive oxygen
      species-mediated signaling pathway.
AB  - Low-power laser therapy in medicine is widespread but the mechanisms are not
      fully understood. It has been suggested that low-power laser irradiation (LPLI)
      could induce photochemical reaction and activate several intracellular signaling
      pathways. Reactive oxygen species (ROS) are considered to be the key secondary
      messengers produced by LPLI. Here, we studied the signaling pathway mediated by
      ROS upon the stimulation of LPLI. Src tyrosine kinases are well-known targets of
      ROS and can be activated by oxidative events. Using a Src reporter based on
      fluorescence resonance energy transfer (FRET) and confocal laser scanning
      microscope, we visualized the dynamic Src activation in Hela cells immediately
      after LPLI. Moreover, Src activation by LPLI was in a dose-dependent manner. The
      increase of Src phosphorylation at Tyr416 was detected by Western blotting. In
      the presence of vitamin C, catalase alone, or the combination of catalase and
      superoxide dismutase (SOD), the activation of Src by LPLI is significantly
      abolished. In contrast, Go6983 loading, a PKC inhibitor, did not affect this
      response. Treatment of Hela cells with exogenous H(2)O(2) also resulted in a
      concentration-dependent activation of Src. These results demonstrated that it was
      ROS that mediated Src activation by LPLI. Cellular viability assay revealed that
      laser irradiation of low doses (</=25 J/cm(2)) promoted Hela cells viability
      while high doses impaired. Therefore, LPLI induces ROS-mediated Src activation
      which may play an important role in biostimulatory effect of LPLI.

PMID- 18615582
TI  - S10 phosphorylation of p27 mediates atRA induced growth arrest in ovarian
      carcinoma cell lines.
AB  - All trans retinoic acid (atRA) has been shown to inhibit the growth of CAOV3
      ovarian carcinoma cells and to elevate the level of p27 cyclin-dependent kinase
      inhibitor. We report here that phosphorylation at S10 residue is an important
      event in mediating p27 role in atRA induced growth arrest. atRA treatment of atRA
      sensitive CAOV3 cells increases the levels of S10 phospho-p27 in both nuclear and
      cytoplasmic cell compartments. This increase is accompanied by a decrease in the
      levels of skp2 protein. This effect was not observed in SKOV3 cells which are
      resistant to atRA growth inhibitory effect. An A10-p27 mutant that cannot be
      phosphorylated at S10 induces a dominant negative effect on the atRA effect on
      the levels and activity of endogenous p27. Overexpression of A10-p27 mutant
      renders CAOV3 cells more resistant to atRA treatment and reverses the effect that
      atRA has on p27 binding to CDKs, on CDK activity, and on the expression of S
      phase genes.

PMID- 18615583
TI  - Sex steroid hormones induce acylation stimulating protein resistance in 3T3-L1
      adipocytes.
AB  - Acylation stimulating protein (ASP) stimulates triglyceride synthesis and glucose
      transport via its receptor C5L2. In human studies, ASP is increased in insulin
      resistant states such as obesity, diabetes, polycystic ovary syndrome and late
      pregnancy (the latter two associated with altered sex hormones). The aims were
      (i) to evaluate ASP response and C5L2 expression following treatment with sex
      steroid hormones and (ii) to identify mechanisms of ASP resistance using 3T3-L1
      adipocytes and preadipocytes. Overnight incubation with physiological
      progesterone (PROG) concentrations induced dose-dependent inhibition of ASP
      stimulated glucose transport in adipocytes (188 +/- 11% +ASP, 100 +/- 4% control,
      129 +/- 18% to 85 +/- 7% [ASP + PROG 10(-8) to 10(-6) M] and preadipocytes (263
      +/- 18% +ASP, 100 +/- 3% control, 170 +/- 11% to 167 +/- 4% [ASP + PROG 10(-8) to
      10(-6) M]), while estradiol and testosterone (TEST) were effective only at the
      highest concentration (10(-6) M). In adipocytes, dose-dependent maximal C5L2 mRNA
      decreases were 39-75% (P = 0.003), with decreased cell-surface C5L2 of -22% and 
      27% (10(-6) M PROG and TEST, respectively) with no change in preadipocytes.
      Adipocytes treated with PROG displayed decreases in G proteins: Gbeta (-55%),
      Galphaq/11 (-56%) as well as complete inhibition of ASP stimulation. PROG
      significantly decreased basal levels of phosphorylated PKCalpha (p-PKCalpha)
      while there was no change in p- PKCzeta. ASP increased p-PKCalpha and PKCzeta to
      161% (P < 0.0.001) and 160% (P < 0.01), a stimulation effectively blocked by PROG
      (10(-8) and 10(-6) M) and TEST (10(-6) M). Sex steroid hormone-induced ASP
      resistance via C5L2 may contribute to altered adipose tissue function and insulin
      resistance phenotype in humans.

PMID- 18615584
TI  - Induction of serum- and glucocorticoid-induced kinase-1 (SGK1) by cAMP regulates
      increases in alpha-ENaC.
AB  - Alpha-ENaC expression and activity is regulated by a variety of hormones
      including beta-adrenergic agonists via the second messenger cAMP. We evaluated
      the early intermediate pathways involved in the up-regulation of SGK1 by DbcAMP
      and whether SGK1 is a prerequisite for induction of alpha-ENaC expression.
      Submandibular gland epithelial (SMG-C6) cells treated with DbcAMP (1 mM) induced
      both SGK1 mRNA and protein expression. DbcAMP-stimulated SGK1 mRNA expression was
      decreased by actinomycin D and mRNA and protein expressions were attenuated by
      PKA inhibitors (H-89 and KT5720). Inhibition of PI3-K with either LY294002 or
      dominant negative PI3-K reduced DbcAMP-stimulated SGK1 protein and mRNA levels,
      attenuated the phosphorylation of CREB (a cAMP-activated transcription factor)
      and decreased alpha-ENaC protein levels and Na(+) transport. In addition, the
      combination of PKA inhibitors with dominant negative PI3-K synergistically
      inhibited DbcAMP-induced Na(+) transport. Inhibition of SGK1 expression by siRNA
      decreased but did not obliterate DbcAMP-induced alpha-ENaC expression. Thus, in a
      cell line which endogenously exhibits minimal alpha-ENaC expression, induction of
      SGK1 by DbcAMP occurs via the PI3-K and PKA pathways. Increased alpha-ENaC levels
      and function are partly dependent upon the early induction of SGK1 expression.

PMID- 18615585
TI  - Age-related differences in insulin-like growth factor-1 receptor signaling
      regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cells.
AB  - Advanced age is a major risk factor for atherosclerosis, but how aging per se
      influences pathogenesis is not clear. Insulin-like growth factor-1 receptor (IGF
      1R) promotes aortic vascular smooth muscle cell (VSMC) growth, migration, and
      extracellular matrix formation, but how IGF-1R signaling changes with age in VSMC
      is not known. We previously found age-related differences in the activation of
      Akt/FOXO3a and ERK1/2 pathways in VSMC, but the upstream signaling remains
      unclear. Using explanted VSMC from Fischer 344/Brown Norway F1 hybrid rats shown
      to display age-related vascular pathology similar to humans, we compared IGF-1R
      expression in early passages of VSMC and found a constitutive activation of IGF
      1R in VSMC from old compared to young rats, including IGF-1R expression and its
      tyrosine kinase activity. The link between IGF-1R activation and the Akt/FOXO3a
      and ERK pathways was confirmed through the induction of IGF-1R with IGF-1 in
      young cells and attenuation of IGF-1R with an inhibitor in old cells. The effects
      of three kinase inhibitors: AG1024, LY294002, and TCN, were compared in VSMC from
      old rats to differentiate IGF-1R from other upstream signaling that could also
      regulate the Akt/FOXO and ERK pathways. Genes for p27kip-1, catalase and MnSOD,
      which play important roles in the control of cell cycle arrest and stress
      resistance, were found to be FOXO3a-targets based on FOXO3a-siRNA treatment.
      Furthermore, IGF-1R signaling modulated these genes through activation of the
      Akt/FOXO3a pathway. Therefore, activation of IGF-1R signaling influences VSMC
      function in old rats and may contribute to the increased risk for
      atherosclerosis.

PMID- 18615587
TI  - Wnt5a induces homodimerization and activation of Ror2 receptor tyrosine kinase.
AB  - Wnts are secreted glycoproteins that control vital biological processes,
      including embryogenesis, organogenesis and tumorigenesis. Wnts are classified
      into several subfamilies depending on the signaling pathways they activate, with
      the canonical subfamily activating the Wnt/beta-catenin pathway and the non
      canonical subfamily activating a variety of other pathways, including the
      Wnt/calcium signaling and the small GTPase/c-Jun NH2-terminal kinase pathway.
      Wnts bind to a membrane receptor Frizzled and a co-receptor, the low-density
      lipoprotein receptor related protein. More recently, both canonical and non
      canonical Wnts were shown to bind the Ror2 receptor tyrosine kinase. Ror2 is an
      orphan receptor that plays crucial roles in skeletal morphogenesis and promotes
      osteoblast differentiation and bone formation. Here we examine the effects of a
      canonical Wnt3a and a non-canonical Wnt5a on the signaling of the Ror2 receptor.
      We demonstrate that even though both Wnt5a and Wnt3a bound Ror2, only Wnt5a
      induced Ror2 homo-dimerization and tyrosine phosphorylation in U2OS human
      osteoblastic cells. Furthermore, Wnt5a treatment also resulted in increased
      phosphorylation of the Ror2 substrate, 14-3-3beta scaffold protein, indicating
      that Wnt5a binding causes activation of the Ror2 signaling cascade. Functionally,
      Wnt5a recapitulated the Ror2 activation phenotype, enhancing bone formation in
      the mouse calvarial bone explant cultures and potentiating osteoblastic
      differentiation of human mesenchymal stem cells. The effect of Wnt5a on
      osteoblastic differentiation was largely abolished upon Ror2 down-regulation.
      Thus we show that Wnt5a activates the classical receptor tyrosine kinase
      signaling cascade through the Ror2 receptor in cells of osteoblastic origin.

PMID- 18615586
TI  - Single-molecule analysis of chromatin: changing the view of genomes one molecule
      at a time.
AB  - Wrapping DNA into chromatin provides a wealth of regulatory mechanisms that
      ensure normal growth and development in eukaryotes. Our understanding of
      chromatin structure, including nucleosomes and non-histone protein-DNA
      interactions, has benefited immensely from nuclease and chemical digestion
      techniques. DNA-bound proteins, such as histones or site-specific factors,
      protect DNA against nuclease cleavage and generate large nucleosomal or small
      regulatory factor footprints. Chromatin subject to distinct modes of regulation
      often coincides with sites of nuclease hypersensitivity or nucleosome
      positioning. An inherent limitation of cleavage-based analyses has been the
      inability to reliably analyze regions of interest when levels of digestion depart
      from single-hit kinetics. Moreover, cleavage-based techniques provide views that
      are averaged over all the molecules in a sample population. Therefore, in cases
      of occupancy of multiple regulatory elements by factors, one cannot define
      whether the factors are bound to the same or different molecules in the
      population. The recent development of DNA methyltransferase-based, single
      molecule MAP-IT technology overcomes limitations of ensemble approaches and has
      opened numerous new avenues in chromatin research. Here, we review the strengths,
      limitations, applications and future prospects of MAP-IT ranging from structural
      issues to mechanistic questions in eukaryotic chromatin regulation.

PMID- 18615589
TI  - Glycogen synthase kinase-3beta regulates DeltaNp63 gene transcription through the
      beta-catenin signaling pathway.
AB  - Overexpression of DeltaNp63 has been observed in a number of human cancers,
      suggesting a role for DeltaNp63 in carcinogenesis. In the present study, we show
      that inhibition of glycogen synthase kinase-3beta (GSK-3beta) by lithium chloride
      (LiCl) elicited a stimulatory effect on DeltaNp63 promoter activity in HEK 293T
      cells. Exposure to LiCl induced DeltaNp63 promoter activation as well as
      DeltaNp63 protein expression in the cells. The effect of GSK-3beta on DeltaNp63
      expression was further confirmed by the use of two highly specific GSK-3beta
      inhibitors, SB216763 and SB415286. Further study showed the presence of a
      putative beta-catenin responsive element (beta-catenin-RE) in the DeltaNp63
      promoter region, and the stimulation of DeltaNp63 promoter activity by GSK-3beta
      inhibitor is markedly abolished by mutation or deletion of the putative beta
      catenin-RE. Data are also presented to show that beta-catenin acts together with
      Lef-1 to influence DeltaNp63 promoter activity and protein expression.

PMID- 18615588
TI  - Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR)
      and induces lower teratogenicity in MTHFR deficiency.
AB  - Valproate (VPA) treatment in pregnancy leads to congenital anomalies, possibly by
      disrupting folate or homocysteine metabolism. Since methylenetetrahydrofolate
      reductase (MTHFR) is a key enzyme of folate interconversion and homocysteine
      metabolism, we addressed the possibility that VPA might have different
      teratogenicity in Mthfr(+/+) and Mthfr(+/-) mice and that VPA might interfere
      with folate metabolism through MTHFR modulation. Mthfr(+/+) and Mthfr(+/-)
      pregnant mice were injected with VPA on gestational day 8.5; resorption rates and
      occurrence of neural tube defects (NTDs) were examined on gestational day 14.5.
      We also examined the effects of VPA on MTHFR expression in HepG2 cells and on
      MTHFR activity and homocysteine levels in mice. Mthfr(+/+) mice had increased
      resorption rates (36%) after VPA treatment, compared to saline treatment (10%),
      whereas resorption rates were similar in Mthfr(+/-) mice with the two treatments
      (25-27%). NTDs were only observed in one group (VPA-treated Mthfr(+/+)). In HepG2
      cells, VPA increased MTHFR promoter activity and MTHFR mRNA and protein (2.5- and
      3.7-fold, respectively). Consistent with cellular MTHFR upregulation by VPA,
      brain MTHFR enzyme activity was increased and plasma homocysteine was decreased
      in VPA-treated pregnant mice compared to saline-treated animals. These results
      underscore the importance of folate interconversion in VPA-induced
      teratogenicity, since VPA increases MTHFR expression and has lower teratogenic
      potential in MTHFR deficiency.

PMID- 18615590
TI  - Genetic and epigenetic regulation in nuclear microenvironments for biological
      control in cancer.
AB  - The regulatory machinery that governs genetic and epigenetic control of gene
      expression is compartmentalized in nuclear microenvironments. Temporal and
      spatial parameters of regulatory complex organization and assembly are
      functionally linked to biological control and are compromised with the onset and
      progression of tumorigenesis providing a novel platform for cancer diagnosis and
      treatment.

PMID- 18615591
TI  - Placenta growth factor, PLGF, influences the motility of lung cancer cells, the
      role of Rho associated kinase, Rock1.
AB  - Placenta growth factor (PlGF) is a member of the VEGF family and has been
      implicated in the aggressive capacity of solid tumours, partly via its impact on
      angiogenesis. The present study determined the direct biological function of
      endogenous PlGF in lung cancer cells. From the human non-small cell lung cancer
      cell line A549 which expressed good level of PlGF, we created sublines within
      which PlGF expression was knockdown by way of anti-PlGF ribozyme transgenes.
      Remarkable reductions of both PlGF mRNA and protein by the ribozyme transgenes
      were revealed in A549 transfectants (A549(DeltaPlGF)) using RT-PCR and Western
      blotting respectively. A549(DeltaPlGF) cells exhibited significantly reduced
      migration and adhesion compared with the wild-type (A549(WT)) and the empty
      plasmid control (A549(pEF/His)) cells. Immunocytochemistry and Western blotting
      further revealed that the expression of ROCK1, Rho associated kinase, was also
      reduced in A549(DeltaPlGF) cells, in comparison with wild-type and control cells.
      In addition, A549(DeltaPlGF) cells lost its response to a ROCK inhibitor, which
      otherwise strongly inhibited the motility of A549(WT) and A549(pEF/His) cells.
      These data indicate that PlGF directly regulates the motility of human lung
      cancer cells and that this regulation critically dependent on ROCK-1. The study
      further indicates that PlGF is a potential therapeutic target in lung cancer.

PMID- 18615593
TI  - Couple therapy with combat veterans and their partners.
AB  - Service members returning from Iraq and Afghanistan face psychological challenges
      that can exert profound effects on families and couples, but can also be treated
      within a systemic context. Couple therapy offers a means of increasing social
      support, decreasing interpersonal conflict, and addressing the experiential
      avoidance that maintains posttraumatic symptoms. For combat veterans and their
      partners, we present an adaptation of integrative behavioral couple therapy
      (IBCT) that reduces conflict and encourages intimacy through acceptance and
      skills strategies. By doing so, IBCT exposes service members in couple therapy to
      emotions, interpersonal situations, and activities that facilitate recovery from
      combat-related distress. We illustrate common presenting problems in this
      population and the utilization of IBCT with a case example.

PMID- 18615592
TI  - Modulation of integrin antagonist signaling by ligand binding of the heparin
      binding domain of vitronectin to the alphaVbeta3 integrin.
AB  - The interaction between the arginine glycine and aspartic acid motif (RGD) of
      integrin ligands such as vitronectin and the integrin receptor alphaVbeta3 in
      mediating cell attachment has been well described. Similarly, the ability of
      disintegrins, small RGD containing peptides, to inhibit cell attachment and other
      cellular processes has also been studied extensively. Recently, we characterized
      a second site of interaction between vitronectin and its integrin partner. We
      determined that amino acids within the heparin-binding domain of vitronectin bind
      to a cysteine loop (C-loop) region of beta3 and that this interaction is required
      for the positive effects of alphaVbeta3 ligand occupancy on IGF-I signaling in
      smooth muscle cells. In this study we examine the signaling events activated
      following ligand binding of disintegrins to the alphaVbeta3 and the ability of
      these signals to be regulated by binding of the heparin-binding domain of
      vitronectin. We demonstrate that disintegrin ligand binding activates a series of
      events including the sequential activation of the tyrosine kinases c-Src and Syk.
      This leads to the activation of calpain and the cleavage of the beta3 cytoplasmic
      tail. Addition of vitronectin or a peptide homologous to the heparin-binding
      domain inhibited activation of this pathway. Our results suggest that the
      signaling events that occur following ligand binding to the alphaVbeta3 integrin
      reflects a balance between the effects mediated through the RGD binding site
      interaction and the effects mediated by the heparin binding site interaction and
      that for intact vitronectin the effect of the heparin-binding domain
      predominates.

PMID- 18615594
TI  - The mineralized osteocyte: a living fossil.
AB  - We report here on an enigmatic and biologically mysterious event in which a
      single cell, the osteocyte, mineralizes in vivo and in this process the cell's
      organelles, cytoskeleton and membrane, are mineralized in a dying state. That the
      bony lacuna in which the lone osteocyte resides becomes infilled with mineral in
      vivo is not a new observation and was noted by early microscopists. This study
      has applied scanning and transmission electron microscopy to modern,
      archaeological, and fossil bone to investigate the mineral and organic structure
      and content of this cell. The results from this study revealed that within this
      mineral lies a visibly identifiable cell, which has an apoptotic-like morphology.
      The mechanisms by which this cell mineralizes are so intimate chemically that
      remnant cell organelles, membranes, cytoskeleton, and potentially nucleic bodies
      are morphologically identifiable. We have further identified mineralized
      osteocytes surviving in archaeological and fossil mammal bone up to 5 million
      years BP. The significance of our findings demonstrates that a single cell may
      itself mineralize in vivo via an unknown set of biochemical events. Importantly,
      the location and survival of extra cellular and cellular proteins, including
      nuclear and mitochondrial DNA in bone after death, has been an area of some
      speculation, and this unique fossil cell provides a preservation locus within
      human and mammalian bone, which might be fruitfully targeted in future
      biomolecular studies.

PMID- 18615595
TI  - Dexamethasone and corticosterone induce similar, but not identical, muscle
      wasting responses in cultured L6 and C2C12 myotubes.
AB  - Dexamethasone-treated L6 (a rat cell line) and C2C12 (a mouse cell line) myotubes
      are frequently used as in vitro models of muscle wasting. We compared the effects
      of different concentrations of dexamethasone and corticosterone (the naturally
      occurring glucocorticoid in rodents) on protein breakdown rates, myotube size,
      and atrogin-1 and MuRF1 mRNA levels in the two cell lines. In addition, the
      expression of the glucocorticoid receptor (GR) and its role in glucocorticoid
      induced metabolic changes were determined. Treatment with dexamethasone or
      corticosterone resulted in dose-dependent increases in protein degradation rates
      in both L6 and C2C12 myotubes accompanied by 25-30% reduction of myotube
      diameter. The same treatments increased atrogin-1 mRNA levels in L6 and C2C12
      myotubes but, surprisingly, upregulated the expression of MuRF1 in L6 myotubes
      only. Both cell types expressed the GR and treatment with dexamethasone or
      corticosterone downregulated total cellular GR levels while increasing nuclear
      translocation of the GR in both L6 and C2C12 myotubes. The GR antagonist RU38486
      inhibited the dexamethasone- and corticosterone-induced increases in atrogin-1
      and MuRF1 expression in L6 myotubes but not in C2C12 myotubes. Interestingly,
      RU38486 exerted agonist effects in the C2C12, but not in the L6 myotubes. The
      present results suggest that muscle wasting-related responses to dexamethasone
      and corticosterone are similar, but not identical, in L6 and C2C12 myotubes. Most
      notably, the regulation by glucocorticoids of MuRF1 and the role of the GR may be
      different in the two cell lines. These differences need to be taken into account
      when cultured myotubes are used in future studies to further explore mechanisms
      of muscle wasting.

PMID- 18615596
TI  - Flow cytometry histograms: transformations, resolution, and display.
AB  - Flow cytometry data analysis routinely includes the use of one- or two-parameter
      histograms to visualize the data. These histograms have traditionally been
      plotted with either a linear or logarithmic scale. However, the recent trend of
      performing the logarithmic conversion in software has made apparent some
      limitations of the traditional visual presentation of logarithmic data. This
      review discusses the mathematics of presenting data on a histogram and emphasizes
      the difference between scaling and binning. The review introduces the concept of
      an effective resolution to describe how the bin width changes in a variable bin
      width histogram. The change in effective resolution is used to explain the
      commonly observed valley and picket fencing artifacts. These result from the
      effective resolution of the display histogram being too high for the data being
      presented. Recently, several different binning transformations have been
      described that are becoming more popular because they allow one to view a large
      dynamic range of data on a single plot, while allowing the display of negative
      data values. While each of the transforms is based upon different equations, they
      all exhibit very similar properties. All of the transforms bin the data
      logarithmically at high channel values and linearly at low channel values. The
      linear scaling of the lower channels serves to limit the effective resolution of
      the histogram, thus minimizing the valley and picket fencing artifacts. The newer
      transformations are not without their own limitations and recommendations for the
      appropriate manner of presenting flow cytometry data using these newer
      transformations are discussed.

PMID- 18615597
TI  - Flow cytometric detection of perforin upregulation in human CD8 T cells.
AB  - Perforin and granzymes work synergistically to induce apoptosis in target cells
      recognized by cytotoxic T lymphocytes. While perforin is readily detectable by
      flow cytometry in resting CD8 T cells, upregulation of perforin in activated
      cells is thought to require proliferation. However, perforin undergoes numerous
      conformational changes during its maturation, which may affect the ability of
      conventional antibodies to recognize newly synthesized perforin. Polychromatic
      flow cytometry was used to detect perforin and cytokine production following
      stimulation of ex vivo human CD8 T cells. Two different anti-perforin antibodies,
      clones B-D48 and deltaG9, were used to discriminate various forms of perforin
      after cellular activation. We provide evidence for the rapid upregulation of
      perforin protein, which may contribute to the ability of CD8 T cells to kill
      multiple targets over time. The deltaG9 clone recognizes the granule-associated
      conformation of perforin, while the B-D48 clone is able to detect perforin in
      multiple forms. Finally, we show there is variability in the ability of CD8 T
      cells to upregulate perforin. Human CD8 T cells are capable of new perforin
      production immediately following activation. This work defines a novel flow
      cytometric procedure that can be used to more completely assess the cytotoxic
      capacity of human CD8 T cells.

PMID- 18615598
TI  - Development of an automated analysis system for data from flow cytometric
      intracellular cytokine staining assays from clinical vaccine trials.
AB  - Intracellular cytokine staining (ICS) by multiparameter flow cytometry is one of
      the primary methods for determining T-cell immunogenicity in HIV-1 clinical
      vaccine trials. Data analysis requires considerable expertise and time. The
      amount of data is quickly increasing as more and larger trials are performed, and
      thus there is a critical need for high-throughput methods of data analysis. A web
      based flow cytometric analysis system, LabKey Flow, was developed for the
      analyses of data from standardized ICS assays. Using a gating template created
      manually in commercially available flow cytometric analysis software, the system
      automatically compensates and analyzes all data sets. Quality control queries
      were designed to identify potentially incorrect sample collections. Comparison of
      the semiautomated analysis performed by LabKey Flow and the manual analysis
      performed using FlowJo software demonstrated excellent concordance (concordance
      correlation coefficient > 0.990). Manual inspection of the analyses performed by
      LabKey Flow for eight-color ICS data files from several clinical vaccine trials
      indicated that template gates can appropriately be used for most data sets. Thus,
      the semiautomated LabKey Flow analysis system can accurately analyze large ICS
      data files. Routine use of the system does not require specialized expertise.
      This high-throughput analysis will provide great utility for rapid evaluation of
      complex multiparameter flow cytometric measurements collected from large clinical
      trials.

PMID- 18615599
TI  - Comparative study of human erythrocytes by digital holographic microscopy,
      confocal microscopy, and impedance volume analyzer.
AB  - Red blood cell (RBC) parameters such as morphology, volume, refractive index, and
      hemoglobin content are of great importance for diagnostic purposes. Existing
      approaches require complicated calibration procedures and robust cell
      perturbation. As a result, reference values for normal RBC differ depending on
      the method used. We present a way for measuring parameters of intact individual
      RBCs by using digital holographic microscopy (DHM), a new interferometric and
      label-free technique with nanometric axial sensitivity. The results are compared
      with values achieved by conventional techniques for RBC of the same donor and
      previously published figures. A DHM equipped with a laser diode (lambda = 663 nm)
      was used to record holograms in an off-axis geometry. Measurements of both RBC
      refractive indices and volumes were achieved via monitoring the quantitative
      phase map of RBC by means of a sequential perfusion of two isotonic solutions
      with different refractive indices obtained by the use of Nycodenz (decoupling
      procedure). Volume of RBCs labeled by membrane dye Dil was analyzed by confocal
      microscopy. The mean cell volume (MCV), red blood cell distribution width (RDW),
      and mean cell hemoglobin concentration (MCHC) were also measured with an
      impedance volume analyzer. DHM yielded RBC refractive index n = 1.418 +/- 0.012,
      volume 83 +/- 14 fl, MCH = 29.9 pg, and MCHC 362 +/- 40 g/l. Erythrocyte MCV,
      MCH, and MCHC achieved by an impedance volume analyzer were 82 fl, 28.6 pg, and
      349 g/l, respectively. Confocal microscopy yielded 91 +/- 17 fl for RBC volume.
      In conclusion, DHM in combination with a decoupling procedure allows measuring
      noninvasively volume, refractive index, and hemoglobin content of single-living
      RBCs with a high accuracy.

PMID- 18615600
TI  - Temozolomide for recurrent low-grade spinal cord gliomas in adults.
AB  - BACKGROUND: There is no standard therapy for surgery- and radiotherapy-resistant,
      recurrent, low-grade spinal cord gliomas. Therefore, a retrospective study of
      temozolomide (TMZ) in adults with recurrent low-grade spinal cord gliomas with a
      primary objective of determining progression-free survival (PFS) was performed.
      METHODS: Twenty-two patients (11 men and 11 women) aged 20 years to 55 years
      (median, 35 years) with recurrent spinal cord gliomas (World Health Organization
      grade 2 astrocytoma in 19 patients and oligoastrocytoma in 3 patients) were
      treated. All had previously been treated with surgery and involved-field
      radiotherapy. Thirteen patients underwent repeat surgery. All patients were
      chemotherapy-naive. TMZ was administered at a dose of 150-200 mg/m(2)/day for 5
      consecutive days every 4 weeks (operationally defined as a single cycle).
      Neurologic and neuroradiographic evaluations were performed every 8 weeks.
      RESULTS: All patients were evaluable for toxicity and response. A total of 266
      cycles of TMZ (median, 14 cycles; range, 2 cycles-24 cycles) was administered.
      TMZ-related toxicity included constipation (9 patients, 1 with grade 3),
      lymphopenia (9 patients, 1 with grade 3), fatigue (7 patients, 1 with grade 3),
      neutropenia (6 patients, 2 with grade 3), and thrombocytopenia (6 patients, 2
      with grade 3). Four (18%) patients demonstrated a partial radiographic response,
      12 (55%) demonstrated stable disease, and 6 (27%) had progressive disease after 2
      cycles of TMZ. Time to tumor progression ranged from 2 months to 28 months
      (median, 14.5 months). Survival ranged from 4 months to 39 months (median, 23
      months). PFS at 6 months, 12 months, 18 months, and 24 months was 64%, 64%, 41%,
      and 27%, respectively. CONCLUSIONS: TMZ demonstrated modest efficacy with
      acceptable toxicity in this cohort of adult patients with recurrent low-grade
      spinal cord gliomas.

PMID- 18615601
TI  - Pilot clinical trial of localized concurrent chemoradiation therapy for locally
      advanced hepatocellular carcinoma with portal vein thrombosis.
AB  - BACKGROUND: Patients with advanced hepatocellular carcinoma (HCC) with portal
      vein thrombosis (PVT) have a particularly grave prognosis. In the current study,
      an attempt was made to localize chemoradiation therapy (CCRT) followed by hepatic
      arterial infusion chemotherapy (HAIC) in patients with locally advanced HCC with
      PVT and good reserve liver function. The objective of the current study was to
      evaluate the therapeutic effect of localized CCRT followed by HAIC as a new
      treatment modality for these patients. METHODS: Between January 1998 and December
      2003, 40 patients were recruited. Concurrent regional chemotherapy using an intra
      arterial implanted port plus localized external beam radiotherapy was performed
      with a total of 45 gray (Gy) over 5 weeks with conventional fractionation and
      hepatic arterial infusion of 5-fluorouracil (5-FU), which was administered during
      the first and fifth weeks of radiotherapy. One month after localized CCRT, HAIC
      with 5-FU and cisplatin was administered every 4 weeks. RESULTS: One month after
      localized CCRT, an objective response was observed on the intention-to-treat
      analysis in 18 of 40 patients (45%). The actuarial 3-year overall survival rate
      was 24.1% and the median survival time was 13.1 months from the start of
      radiation treatment. Responders after localized CCRT demonstrated significantly
      better survival (P = .033) than nonresponders. CONCLUSIONS: The substantial
      response rate as well as median survival time noted in the current study
      encourages the use of this new approach in patients with locally advanced HCC
      with PVT.

PMID- 18615603
TI  - The influence of polyalcohols and carbohydrates on the thermostability of alpha
      amylase.
AB  - The influence of polyhydric alcohols and carbohydrates on the thermostability,
      i.e., the heat inactivation kinetics, of Bacillus licheniformis alpha-amylase was
      studied in the temperature range 96 degrees to 130 degrees C. High concentrations
      (from 9 to 60 weight percent) of glycerol, sorbitol, mannitol, sucrose, or starch
      can markedly decrease the inactivation rate constant, k, and in the studied
      cases, this stabilizing effect grows stronger with increasing additive
      concentration. Statements about stabilization should, however, be specified
      carefully with respect to temperature, because E(A) is mostly altered likewise.
      For dissolved enzyme E(A) was almost always decreased in the presence of polyol
      or carbohydrate, whereas for immobilized enzyme it was augmented in each studied
      instance. The inactivation of dissolved enzyme can, in all the studied cases, be
      adequately described as a first-order process. Immobilized enzyme, however, shows
      biphasic then first-order inactivation kinetics, depending on the additive
      concentration and temperature.

PMID- 18615604
TI  - Effect of solution environment on the permeability of red blood cells.
AB  - The cell membrane permeability governs the rate of solute transport into and out
      of the cell, significantly affecting the cell's metabolic processes, viability,
      and potential usefulness in both biotechnological applications and physiological
      systems. Most previous studies of the cell membrane permeability have neglected
      the possible effects of suspending medium on membrane transport, even though
      there is extensive experimental evidence that suspending phase composition can
      significantly affect other properties related to the cell membrane (e.g., cell
      deformability, fragility, and aggregation rate). This study examined the effects
      of suspending phase composition (both proteins and electrolytes) on the
      permeability of human red blood cells to the metabolites creatinine and uric
      acid. Data were obtained using a stirred ultrafiltration device with direct cell-
      and proteinfree sampling through a semipermeable membrane. Both the uric acid and
      creatinine permeabilities were strongly affected by the suspending phase
      composition, with the permeabilities in different buffer solutions varying by as
      much as a factor of three. The predominant factors affecting the permeability
      were the presence (or absence) of chloride, phosphate/adenine, and proteins,
      although the magnitude and even the direction of these effects were significantly
      different for creatinine and uric acid transport. The dramatic differences in
      behavior for uric acid and creatinine reflect the different transport mechanisms
      for these solutes, with uric acid transported by a carrier-mediated mechanism and
      creatinine transported by passive diffusion through the lipid bilayer. These
      results provide important insights into the effects of solution environment on
      cell membrane transport and other cell membrane-mediated properties.

PMID- 18615605
TI  - Mass transfer effects in solvent-free fat interesterification reactions:
      influences on catalyst design.
AB  - The use of solvent-free systems in the oil and fats industry is commonplace.
      Initial studies on interesterification were carried out in solvent systems
      because the lipase was immobilized solely by adsorption onto particles of
      diatomaceous earth. In this study, the mass transfer characteristics associated
      with the continuous interesterification of olive oil in a solvent-free system
      have been examined, for lipase immobilized on the three ion-exchange materials:
      Duolite ES562, Duolite ES568, and Spheroil DEA. The process of immobilization is
      influenced by the internal structure of the material and this in turn influences
      the interesterification activity of the catalyst. Individually prepared catalysts
      for the three support materials have shown that external mass transfer
      limitations are unlikely even at low flowrates.In the case of Spherosil DEA, with
      a mean pore diameter of 1480 A, the wide pores would be expected to reduce
      internal mass transfer limitations; however, it is more likely that the reduction
      in activity with increased catalyst loading is due to the lipase molecules being
      immobilized in a tightly packed monolayer. In such a situation, some active sites
      of the lipase molecules would become inaccessible to substrate molecules leading
      to an observed reduction in activity. For Duolite ES568, the observed results are
      very similar to those seen for Spherosil DEA, however, the pore structure of this
      support material indicate that some internal mass transfer limitations may also
      be occurring. Yet the contribution of the individual effects cannot be
      determined. The results observed for the support Duolite ES562 are different than
      those observed for the other materials and reflect the heterogeneity of Duolite
      ES562. The large proportion of narrow pores in the support mean that, for the
      catalysts examined, immobilization is most likely to have occurred in the
      external pores of the particles, and as such no internal mass transfer limitation
      is observed.It is clear that for interesterification the material chosen for
      enzyme immobilization will have an important role in determining the catalyst
      efficiency. External mass transfer limitations are very minor and observed
      internal mass transfer limitations may be caused by both internal mass transfer
      and the manner in which the immobilization process occurs.

PMID- 18615606
TI  - Oxygen uptake and citric acid production by Candida lipolytica Y 1095.
AB  - The rates of oxygen uptake and oxygen transfer during cell growth and citric acid
      production by Candida lipolytica Y 1095 were determined. The maximum cell growth
      rate, 1.43 g cell/L x h, and volumetric oxygen uptake rate, 343 mg O(2)/L x h,
      occurred approximately 21 to 22 h after inoculation. At the time of maximum
      oxygen uptake, the biomass concentration was 1.3% w/v and the specific oxygen
      uptake rate was slightly greater than 26 mg O(2)/g cell x h. The specific oxygen
      uptake rate decreased to approximately 3 mg O(2)/g cell x h by the end of the
      growth phase.During citric acid production, as the concentration of dissolved
      oxygen was increased from 20% to 80% saturation, the specific oxygen uptake and
      specific citric acid productivity (mg citric acid/g cell x h) increased by 160%
      and 71%, respectively, at a biomass concentration of 3% w/v. At a biomass
      concentration of 5% w/v, the specific oxygen uptake and specific citric acid
      productivity increased by 230% and 82%, respectively, over the same range of
      dissolved oxygen concentrations.The effect of dissolved oxygen on citric acid
      yields and productivities was also determined. Citric acid yields appeared to be
      independent of dissolved oxygen concentration during the initial production
      phase; however, volumetric productivity (g citric acid/L x h) increased sharply
      with an increase in dissolved oxygen. During the second or subsequent production
      phase, citric acid yields increased by approximately 50%, but productivities
      decreased by roughly the same percentage due to a loss of cell viability under
      prolonged nitrogen-deficient conditions.

PMID- 18615607
TI  - Toward a self-similar theory of microbial populations.
AB  - A fresh quest is made of segregated cell models of microbial populations with a
      view to determine whether the multivarite distribution of physiological states,
      during transient growth, can attain self-similar forms (i.e., become time
      invariant) when each physiological state variable is scaled with respect to its
      population average. Such self-similar growth situations are believed to be more
      general than those of balanced growth. The conditions under which self-similarity
      is possible are investigated. Thus conditions are stipulated on the synthesis
      rates of different physiological entities, cell division rate, and the
      partitioning of the parent cell's components among the daughter cells (assuming
      binary division) in order for self-similar growth to be attained. Subject to the
      attainment of self-similar growth, it is shown that cytometric data can be
      analyzed systematically to determine how the rates of syntheses of various
      biochemical entities and cell division rates vary with the physiological entities
      that are measured. Inverse problems, represented by algebraic systems, are
      identified which will potentially allow flow cytometric data to be inverted to
      yield quantitative information on the absolute rates of cellular growth and
      reproductory processes as a function of the cell states chosen for measurement.
      It is suggested that the methods become more effective when cytometry can be used
      to make direct observations on dividing cells so that the number of unknowns in
      the inverse problem can be reduced, thus facilitating its more complete solution.
      Preliminary analysis of cytometric data obtained in the literature show promise
      of self-similarity and thus the possibility of application of the methods
      discussed here.

PMID- 18615608
TI  - A method for simultaneous determination of solubility and transfer coefficient of
      oxygen in aqueous media using off-gas mass spectrometry.
AB  - A static method was developed that simultaneously determined the solubility of
      oxygen and the oxygen-transfer coefficient in a stirred bioreactor. It was based
      on the static method developed by van Sonsbeek et al. to determine the ka in a
      liquid-impelled loop reactor. Only physical properties of the liquid were used to
      determine both parameters using a mass spectrometer. Data about the solubility of
      oxygen in water are available from the literature. Therefore, the solubility of
      oxygen in water was used to compare our data with published data. Furthermore,
      the solubility of oxygen in trypticase soy broth was compared to literature data.
      No significant deviations between our data and literature data could be observed.
      Our static method and the commonly applied dynamic method to determine the oxygen
      transfer coefficient yielded similar results. The effect of temperature on the
      oxygen-transfer coefficient could be expressed as the activation energy needed
      for the transition of oxygen from the gas to the water phase. This was verified
      using the Arrhenius equation.

PMID- 18615609
TI  - Differences in response of Zymomonas mobilis and Saccharomyces cerevisiae to
      change in extracellular ethanol concentration.
AB  - In high cell density batch fermentations, Zymomonas mobilis produced 91 g L(-1)
      ethanol in 90 min but culture viability fell significantly. Similar viability
      losses in rapid fermentations by yeast have recently been shown to be
      attributable in part to the high rate of change of the extracellular ethanol
      concentration. However, in simulated rapid fermentations in which ethanol was
      pumped continuously to low cell density Z. mobilis suspensions, increases in the
      rate of change of ethanol concentration in the range 21-83 g L(-1) h(-1) did not
      lead to accelerated viability losses. The lag phase of Zymomonas cultures exposed
      to a 30-g L(-1) step change in ethanol concentration was much shorter than that
      of Saccharomyces cerevisiae, providing evidence that the comparative
      insensitivity of Zymomonas to high rates of change of ethanol concentration is
      due to its ability to adapt to changes in ethanol concentration more rapidly than
      yeast.

PMID- 18615610
TI  - Scaleup of spinfilter perfusion bioreactor for mammalian cell retention.
AB  - A spinning cylindrical filter, known as a spinfilter, permits the mammalian cell
      bioreactor operation at high perfusion rates leading to very high cell densities
      (10(7) mL(-1)). Filter screens with openings (25 mum) slightly larger than the
      average cell size have been used to retain single cells in suspension over a long
      period of operation without clogging. We have previously shown why it is
      necessary to optimize the rotational speed of the spinfilter in order to achieve
      efficient cell retention and avoid potential screen clogging. Effects of bulk
      mixing and perfusion rate on screen fouling and cell retention were also
      investigated. Based on this analysis, in this article, we suggest strategies for
      scaleup of spinfilters. Experimental data from 12- and 175-L (working volume)
      bioreactors is shown in support of the scaleup analysis.

PMID- 18615611
TI  - A new visualization chamber to study the transient volumetric response of yeast
      cells submitted to osmotic shifts.
AB  - A visualization chamber has been developed to analyze potential correlations
      between osmotic step increase on yeasts and the resultant cell volume decreases.
      Image analysis was used to characterize the step increases in the center of the
      chamber and to measure the changes in the cell volume. Step increases of
      different intensities have been performed on the yeast Saccharomyces cerevisiae.
      This device has allowed the kinetics of the volumetric evolution of the cells to
      be observed. The water exit flow rate from the cell was found to occur in the
      first 10 s following the hypertonic step change. Comparison of the time constants
      of the chamber and of the cell volume variations allowed to conclude that the
      time constant of the water transfer across the membrane was short (about 1 s).

PMID- 18615612
TI  - Kinetic modeling of interesterification reactions catalyzed by immobilized
      lipase.
AB  - Kinetic data for lipase-catalyzed interesterification reactions between free
      fatty acids and triglycerides were collected and the dynamics of the
      interesterification reactions were successfully modeled using tow rate
      experssions requiring a total of five adjustable parameters. One rate expression
      describes the disappearance of the free fatty acid (octanoic or linolenic acid),
      and the second describes the rate of release of fatty acid residues from the
      triglycerides (olive oil or milkfat). This model is able to account for the
      effects of the concentration of all chemical species participating in
      interesterification throughout the entire reaction. When the data for both
      milkfat and olive oil were subjected to nonlinear regression analyses using the
      same mathematical model, the parameter estimates for both systems were
      comparable. In addition to reproducing the tendencies observed experimentally,
      simulations of the interesterification system under a variety of initial
      conditions provided insight into the effects of several reaction variables which
      could not be examined experimentally. Among the most significant findings of the
      simulation work are (1) there is a limit beyond which increasing the initial
      concentration of water produces no further increase in the initial rate of the
      interesterification reaction; (2) an increase in the initial concentration of
      lower glycerides produces a concomitant increase in the rate of the
      interesterification reaction; (3) the free fatty acids inhibit the rate of
      hydrolysis of the fatty acid residues of the triglycerides; (4) there is a limit
      beyond which increasing the initial concentration of triglycerides produces no
      significant increase in the rate of either the hydrolysis reaction or the
      interesterification reaction.

PMID- 18615613
TI  - Diffusivity of Cu2+ in calcium alginate gel beads.
AB  - The diffusivity of Cu(2+) in calcium alginate beads calculated by the shrinking
      core model (SCM) was reevaluated in this work. The results obtained in this work
      were significantly different than those by the original authors. There were
      excellent agreements between the results obtained by the SCM in this work and
      those by the more rigorous linear absorption model (LAM) by the original authors.

PMID- 18615614
TI  - Diffusivity of Cu2+ in calcium alginate gel beads: recalculation.
AB  - Calculations of the diffusivity of Cu(2+) in calcium alginate gel beads using the
      shrinking core model were checked by us. Corrected results are reported here.
      Diffusivity was still found to increase with increasing alginate concentration,
      but at a lower rate than reported in the cited paper. The diffusivity increased
      by a factor of 2 over the range of alginate concentrations studied rather than
      10. The original data is included with sample calculations.

PMID- 18615615
TI  - Genomic organization of the para-sodium channel alpha-subunit genes from the
      pyrethroid-resistant and -susceptible strains of the diamondback moth.
AB  - We examined the genomic organization of the para-sodium channel alpha-subunit
      gene of the diamondback moth, Plutella xylostella (L.). The nucleotide sequence
      contained 34 putative exons, which covered almost the entire coding region of the
      gene producing 1,889 amino acid residues. Deduced amino acid identity to the hscp
      locus of Heliothis virescens was 84%. Comparison of deduced amino acid sequences
      of the permethrin-resistant and -susceptible strains showed two substitutions
      other than kdr and super-kdr-like substitutions. They were Ala to Thr (A1060T)
      and Pro to Ser (P1836S) at the linker region of the domains II-III and the
      carboxyl terminus, respectively. Furthermore, we developed PCR amplification
      protocols for the rapid detection of both substitutions.

PMID- 18615616
TI  - Characterization of Anopheles minimus CYP6AA3 expressed in a recombinant
      baculovirus system.
AB  - Metabolism by cytochrome P450 monooxygenases is a major mechanism implicated in
      resistance of insects to insecticides, including pyrethroids. We previously
      isolated the cytochrome P450 CYP6AA3 from deltamethrin-selected resistant strain
      of Anopheles minimus mosquito, a major malaria vector in Thailand. In the present
      study, we further investigated the role of CYP6AA3 enzyme in deltamethrin
      metabolism in vitro. The CYP6AA3 was expressed in Spodoptera frugiperda (Sf9)
      insect cells via baculovirus-mediated expression system. The enzymatic activity
      of CYP6AA3 in deltamethrin metabolism was characterized after being reconstituted
      with An. minimus NADPH-cytochrome P450 reductase and a NADPH-regenerating system.
      The contribution of CYP6AA3 responsible for deltamethrin metabolism was
      determined by measurement of deltamethrin disappearance following the incubation
      period and deltamethrin-derived compounds were detected using combined gas
      chromatography mass spectrometry analysis. 3-Phenoxybenzaldehyde was a major
      product of CYP6AA3-mediated deltamethrin metabolism. Deltamethrin degradation and
      formation of metabolites were NADPH-dependent and inhibited by piperonyl
      butoxide. Deltamethrin was catalyzed by CYP6AA3 with an apparent K(m) of 80.0 +/-
      2.0 and V(max) of 60.2 +/- 3.6 pmol/min/pmol P450. Furthermore, deltamethrin
      cytotoxicity assays by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) and trypan blue dye exclusion were examined in Sf9 insect cells,
      with and without expression of CYP6AA3. Results revealed that CYP6AA3 could play
      a role in detoxifying deltamethrin in the cells. Thus, the results of this study
      support the role of CYP6AA3 in deltamethrin metabolism.

PMID- 18615617
TI  - Cloning and characterization of Bmrunt from the silkworm Bombyx mori during
      embryonic development.
AB  - Pair-rule genes (genes that are expressed only in alternate segments, odd or
      even) play an important role in translating the broad gradients of upstream genes
      into dual segment periodicity for body plan patterning in Drosophila. However,
      homologues of pair-rule genes show a remarkable diversity of expression patterns
      and functions in other insects. We cloned the homologue of runt in the silkworm
      Bombyx mori, an intermediate germband-type insect. Whole-mount in situ
      hybridization revealed three stripes arose one by one before gastrulation at the
      blastoderm stage. Five additional stripes were then generated sequentially as the
      growth zone elongated. Eight stripes appeared in a pair-rule manner with two
      segment periodicity, each of which was confined to the posterior of an odd
      numbered parasegment. The weaker segmental secondary stripes emerged de novo in
      even-numbered parasegments. The Bmrunt transcript vanished before blastokinesis
      and was then expressed again in the whole embryo. RNA interference for Bmrunt
      caused severely truncated, almost completely asegmental defects. This cadual-like
      phenotype suggests that Bmrunt does not function as a pair-rule gene in silkworm
      segmentation. Bmrunt is required for formation of most body segments and axis
      elongation in B. mori.

PMID- 18615618
TI  - Aflatoxin B1 detoxification by CYP321A1 in Helicoverpa zea.
AB  - The polyphagous corn earworm Helicoverpa zea frequently encounters aflatoxins,
      mycotoxins produced by the pathogens Aspergillus flavus and A. parasiticus, which
      infect many of this herbivore's host plants. While aflatoxin B1 metabolism by
      midgut enzymes isolated from fifth instars feeding on control diets was not
      detected, this compound was metabolized by midgut enzymes isolated from larvae
      consuming diets supplemented with xanthotoxin, coumarin, or indole-3-carbinol,
      phytochemicals that are likely to co-occur with aflatoxin in infected host
      plants. Of the two metabolites generated, the main derivative identified in
      midguts induced with these chemicals and in reactions containing heterologously
      expressed CYP321A1 was aflatoxin P1 (AFP1), an O-demethylated product of AFB1. RT
      PCR gel blots indicated that the magnitude of CYP321A1 transcript induction by
      these chemicals is associated with the magnitude of increase in the metabolic
      activities of induced midgut enzymes (coumarin>xanthotoxin>indole 3-carbinol).
      These results indicate that induction of P450s, such as CYP321A1, plays an
      important role in reducing AFB1 toxicity to H. zea. Docking of AFB1 in the
      molecular models of CYP321A1 and CYP6B8 highlights differences in their proximal
      catalytic site volumes that allow only CYP321A1 to generate the AFP1 metabolite.

PMID- 18615620
TI  - HSPB2/MKBP, a novel and unique member of the small heat-shock protein family.
AB  - Although proteins belonging to the sHSP superfamily are diverse in sequence and
      size, most share characteristic features, including 1) a small molecular mass of
      12-43 kDa, 2) a conserved alpha-crystallin domain of 80-100 residues, 3)
      formation of large oligomers, 4) a dynamic quaternary structure, and 5) induction
      by stress conditions and chaperone activity in suppressing protein aggregation.
      HSPB2/MKBP (myotonic dystrophy kinase-bind-protein) retains the structural motif
      of the alpha-crystallin family of HSPs but shows a unique nature compared with
      canonical family members, characterized by gene allocation, specific binding
      partners in skeletal muscle, and unique stress responsiveness. MKBP may be
      involved in the pathogenesis of myotonic dystrophy and contribute to the
      neuropathology in both Alzheimer's disease and hereditary cerebral hemorrhage
      with amyloidosis, Dutch type.

PMID- 18615619
TI  - Combined treatment with pegylated interferon-alpha-2a and dacarbazine in patients
      with advanced metastatic melanoma: a phase 2 study.
AB  - BACKGROUND: Dacarbazine (DTIC) and pegylated interferon (IFN)-alpha-2a have both
      demonstrated some efficacy as single agents in metastatic melanoma. To the
      authors' knowledge, the current study is the first to test a combination of these
      2 agents in a phase 2 trial. METHODS: Twenty-eight patients with stage IV
      melanoma without brain metastases were treated with DTIC (at a dose of 850
      mg/m(2) every 3 weeks) combined with weekly pegylated IFN-alpha-2a at a dose of
      180 microg. The study was initiated to evaluate the efficacy and tolerability of
      the combination. The primary study endpoint was objective response. RESULTS:
      Twenty-five patients were evaluable for response. Two patients (8.0%) achieved a
      complete response that continued for >480 days and 746 days, respectively. Four
      patients (16.0%) demonstrated a partial response, and another patient experienced
      stable disease. Six of 7 nonprogressive patients had either not received
      treatment or had not developed disease progression during adjuvant IFN treatment
      for stage II/III disease. The median duration of response was 236 days, the
      median progression-free survival was 56 days, and the overall survival time was
      403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed
      (according to National Cancer Institute Common Toxicity Criteria). CONCLUSIONS:
      The combination of DTIC and pegylated IFN-alpha-2a was found to be well tolerated
      in patients with metastatic melanoma. The response rate of 24%, including 2 long
      lasting complete responses, is encouraging, but must be confirmed in larger
      trials.

PMID- 18615621
TI  - A partial least-square approach for modeling gene-gene and gene-environment
      interactions when multiple markers are genotyped.
AB  - Genetic association studies achieve an unprecedented level of resolution in
      mapping disease genes by genotyping dense single nucleotype polymorphisms (SNPs)
      in a gene region. Meanwhile, these studies require new powerful statistical tools
      that can optimally handle a large amount of information provided by genotype
      data. A question that arises is how to model interactions between two genes.
      Simply modeling all possible interactions between the SNPs in two gene regions is
      not desirable because a greatly increased number of degrees of freedom can be
      involved in the test statistic. We introduce an approach to reduce the genotype
      dimension in modeling interactions. The genotype compression of this approach is
      built upon the information on both the trait and the cross-locus gametic
      disequilibrium between SNPs in two interacting genes, in such a way as to
      parsimoniously model the interactions without loss of useful information in the
      process of dimension reduction. As a result, it improves power to detect
      association in the presence of gene-gene interactions. This approach can be
      similarly applied for modeling gene-environment interactions. We compare this
      method with other approaches, the corresponding test without modeling any
      interaction, that based on a saturated interaction model, that based on principal
      component analysis, and that based on Tukey's one-degree-of-freedom model. Our
      simulations suggest that this new approach has superior power to that of the
      other methods. In an application to endometrial cancer case-control data from the
      Women's Health Initiative, this approach detected AKT1 and AKT2 as being
      significantly associated with endometrial cancer susceptibility by taking into
      account their interactions with body mass index.

PMID- 18615622
TI  - Triplet combination of gemcitabine, paclitaxel, and carboplatin followed by
      maintenance 5-fluorouracil and folinic acid in patients with metastatic
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a disease that is highly responsive
      to various chemotherapeutic agents. In the metastatic setting, 2-drug combination
      chemotherapy generally provides a response rate of 55% to 75%, and median
      survival of 10 to 12 months. The objective of the current study was to assess the
      efficacy of a 3-drug combination followed by maintenance treatment in patients
      with metastatic NPC. METHODS: Patients with metastatic NPC were treated with a
      combination of gemcitabine at a dose of 1,000 mg/m(2), paclitaxel at a dose of 70
      mg/m(2), and carboplatin at an area under the concentration-time-curve (AUC) of
      2.5 on Days 1 and 8 every 21 days. Patients who achieved partial or complete
      response continued to receive weekly 5-fluorouracil at a dose of 450 mg/m(2) and
      leucovorin at a dose of 30 mg/m(2) for 48 weeks. RESULTS: Twenty-eight patients
      were recruited. Twenty-two (79%) patients had >or=2 sites of disease. Toxicities
      were mainly from bone marrow suppression, with 79% grade 3/4 neutropenia, 32%
      grade 3/4 anemia, and 29% grade 3/4 thrombocytopenia (according to the National
      Cancer Institute Common Toxicity Criteria). The overall response rate to the 3
      drug regimen was 86%, with a complete response rate of 11%. The median duration
      of response was 8 months and the median overall survival was 22 months.
      CONCLUSIONS: This regimen of a 3-drug combination followed by maintenance is
      feasible and has demonstrated an encouraging response rate and overall survival.

PMID- 18615623
TI  - The phosphorylated membrane estrogen receptor and cytoplasmic signaling and
      apoptosis proteins in human breast cancer.
AB  - BACKGROUND: Estrogens play a central role in breast cancer development, and the
      estrogen receptor-alpha (ERalpha) remains the single most important predictor of
      breast cancer prognosis. Therefore, it is crucial to elucidate pathways that may
      contribute to ER signaling in clinical specimens. METHODS: Using extracts of
      fresh invasive ERalpha-positive invasive breast carcinomas, ductal carcinoma in
      situ, and normal glandular breast tissue, the authors performed Western blot
      analyses of the membrane-bound ER, 1 of its phosphorylated isoforms, and
      cytosolic fractions from the same specimens, examining associated proteins
      (Akt/mitogen-activated protein kinase pathways). Western blot analysis and
      immunocapture for the apoptosis and survival factors Bcl-2 agonist of death
      (BAD)/Bcl-2 and BAD/Bcl-xL were also performed. RESULTS: To the authors'
      knowledge, this is the first study to report that ERalpha was phosphorylated in
      the plasma membrane fractions derived from patients' invasive breast carcinomas.
      This was associated with a predominance of phosphorylated BAD and a relative
      reduction in Bcl-2 compared with both normal tissue and ductal carcinoma in situ,
      although such studies in fresh tissue did not corroborate these findings. The
      authors also demonstrated that the BAD/Bcl-2 and BAD/Bcl-xL complexes
      characterized the invasive carcinoma state. CONCLUSIONS: A phosphorylated form of
      the membrane ER was found to characterize the invasive cancer state. This was
      associated with a reduction in BAD/Bcl-2 and BAD/Bcl-xl. These data implicate the
      membrane ERalpha as the in vivo receptor responsible for transcription
      independent cellular responses to estrogens.

PMID- 18615624
TI  - Structural and spectral assignments of six anthraquinone derivatives from the
      mangrove fungus (ZSUH-36).
AB  - A new natural product named 6,8,1'-tri-O-methyl averantin (1) has been isolated
      together with five known anthraquinones 1'-O-methyl averantin (2), 6,8-di-O
      methyl averufin (3) averufin (4), versicolorin C (5) and 6,8-di-O-methyl
      averufanin (6) from a mangrove endophytic fungus ZSUH-36 collected from the South
      China Sea. NMR techniques including COSY, HMQC, and HMBC were used to elucidate
      the structures of these compounds. We report the unambiguous assignments of the
      (1)H and (13)C NMR spectra of the new compound 6,8,1'-tri-O-methyl averantin(1).

PMID- 18615625
TI  - Sensitivity of redox reactions of dyes to variations of conditions created in
      mass spectrometric experiments.
AB  - Redox behaviour of four imidazophenazine dye derivatives under mass spectrometric
      conditions of matrix-assisted laser desorption/ionization (MALDI), laser
      desorption/ionization (LDI) from metal and graphite surface, electrospray, low
      temperature secondary ion mass spectrometry (LT SIMS) and fast atom bombardment
      (FAB) was studied and distinctions in the reduction-dependent spectral patterns
      were analyzed from the point of view of different quantities of protons and
      electrons available for reduction in different techniques. The reduction products
      [M + 2H](+*), [M + 3H](+) and M(-*), [M + H](-) were observed in the positive and
      negative ion modes, respectively, which permitted to suggest independent
      occurrence of reduction and protonation/deprotonation processes. LDI from
      graphite substrate was the only technique that allowed us to obtain abundant
      negative ions of all dye derivatives. The yield of field ionization (FI) or field
      desorption (FD) mechanism to ion formation under LDI from rough graphite surface
      has been addressed. The sensitivity of reduction of the dyes to variation of
      reduction-initiating agents confirms high redox activity of the dyes essential
      for their functioning in natural and artificial systems.

PMID- 18615626
TI  - NMR spectral assignments of isoprenylated flavanones from Sophora tonkinensis.
AB  - The phytochemical investigation of extracts from the roots of Sophora tonkinensis
      yielded three new isoprenylated flavanones, the tonkinochromanes F (2), G (3),
      and H (5), along with four known compounds. Structural elucidation of the
      compounds were established on the basis of spectral data, particularly by the use
      of 1D NMR and several 2D shift-correlated NMR pulse sequences ((1)H-(1)H COSY,
      HSQC, HMBC, and ROESY).

PMID- 18615627
TI  - Kinase domain point mutations in Philadelphia chromosome-positive acute
      lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors.
AB  - BACKGROUND: BCR-ABL kinase domain (KD) mutations are detected in approximately
      45% of patients with imatinib-resistant chronic myeloid leukemia. Patterns of KD
      mutations in Philadelphia chromosome (Ph)-positive acute lympho- blastic leukemia
      (ALL) are less well studied. METHODS: The authors assessed KD mutations in
      patients with recurrent Ph-positive ALL after treatments that included 1 or more
      kinase inhibitors (n = 24 patients) or no prior kinase inhibitor (KI) therapy (n
      = 12 patients). RESULTS: ABL KD mutations were detected by direct sequencing in
      15 of 17 patients (88%) who had recurrent Ph-positive ALL and received prior
      imatinib (n = 16) or dasatinib (n = 1) treatment and in 6 of 7 patients (86%) who
      had resistant/recurrent tumors treated with >or=2 KIs compared with 0 of 12
      patients with recurrent Ph-positive ALL who never received KIs. A restricted set
      of mutations was observed, mostly Y253H and T315I, and were detected on average
      10 months after KI initiation, and mutations were not detected in the initial
      tumor samples before KI therapy in 12 patients who were assessed. Using a more
      sensitive pyrosequencing method, mutations were not detected at codons 315 and
      253 in the diagnostic samples from those 12 patients or in 30 patients with Ph
      positive ALL who never developed recurrent disease. CONCLUSIONS: ABL KD
      mutations, especially at codons 315 and 253, emerged at the time of disease
      recurrence in the vast majority of patients who had Ph-positive ALL and received
      maintenance KI therapy. Thus, the authors concluded that ongoing KI exposure may
      alter the patterns of recurrence and favor the outgrowth of clones with KI
      resistant mutations.

PMID- 18615628
TI  - Increased expression of transketolase-like-1 in papillary thyroid carcinomas
      smaller than 1.5 cm in diameter is associated with lymph-node metastases.
AB  - BACKGROUND: Patients with small papillary thyroid carcinoma (PTC) may have a high
      incidence of regional lymph-node (LN) metastases at presentation, and these are
      considered to be an independent risk factor for tumor recurrence. A mutated
      transketolase transcript (TKTL1) has been found up-regulated in different human
      malignancies, and strong TKTL1 protein expression has been associated with
      aggressiveness and poor patient survival in several epithelial cancers. METHODS:
      TKTL1 protein expression was analyzed in 256 consecutive cases of PTCs <or=1.5 cm
      by immunohistochemistry with a specific anti-TKTL1 antibody. RNA analysis was
      performed by real-time polymerase chain reaction (PCR) in all cases for which
      frozen material was available, which resulted in 55 fragments of PTC. RESULTS:
      Increased levels of TKTL1 transcript were detected in 50 of 55 analyzed tumors
      compared with their corresponding normal tissues. Significant differences in
      TKTL1 transcript levels were found between cases of PTC with and without LN
      metastases. In primary tumors, immunoreactivity for TKTL1 was detected in the
      majority of cases, ranging from 0% to 95.0% (mean, 50.11% +/- 27.75%). A
      significant association was found between TKTL1 protein expression and the
      presence of multifocality, bilaterality, extrathyroidal extension, vascular
      invasion, sclerosis, and LN metastases. In cases with LN metastases, a positive
      correlation was found between the TKTL1 protein expression in primary tumors and
      the number of metastatic LNs as well as the diameter of the largest metastatic
      area in LNs. CONCLUSIONS: These findings suggest that TKTL1 overexpression in PTC
      <or=1.5 cm may be considered a factor that facilitates tumor growth and
      progression.

PMID- 18615629
TI  - Making links: introduction to the special issue.

PMID- 18615631
TI  - Living microlens arrays.
AB  - Both individual cells and sheets of cells exert traction forces on the substrate
      and these forces have been investigated using a wide range of methods. Here we
      compare the mechanical properties of fibroblasts and epithelial cells using a
      novel surface geometry. Living cells are added to a thin film of polystyrene [PS]
      attached to a substrate of crosslinked poly(dimethyl siloxane) [PDMS] microwells.
      The contractile nature of the cells attached to the surface and the compliance of
      the PDMS surface geometry allows the PS thin film to buckle, forming arrays of
      convex microlenses. The resulting curvature of the microlenses allows us to
      determine the applied strain of growing cell sheets. We report that a monolayer
      of epithelial cells exerts more stress on the substrate than fibroblasts and
      attribute this to the collective behavior of the epithelium. By subsequently
      adding different chemical triggers to the system, the contractile nature of the
      cells changes, thus modifying the focal length of the microlenses. Together,
      these findings demonstrate the importance of studying the mechanics of cell
      sheets and also introduce a new design paradigm for advanced materials, offering
      great promise for a range of applications.

PMID- 18615630
TI  - Cortactin branches out: roles in regulating protrusive actin dynamics.
AB  - Since its discovery in the early 1990's, cortactin has emerged as a key signaling
      protein in many cellular processes, including cell adhesion, migration,
      endocytosis, and tumor invasion. While the list of cellular functions influenced
      by cortactin grows, the ability of cortactin to interact with and alter the
      cortical actin network is central to its role in regulating these processes.
      Recently, several advances have been made in our understanding of the interaction
      between actin and cortactin, providing insight into how these two proteins work
      together to provide a framework for normal and altered cellular function. This
      review examines how regulation of cortactin through post-translational
      modifications and interactions with multiple binding partners elicits changes in
      cortical actin cytoskeletal organization, impacting the regulation and formation
      of actin-rich motility structures.

PMID- 18615632
TI  - Role of nonmuscle myosin IIB and N-RAP in cell spreading and myofibril assembly
      in primary mouse cardiomyocytes.
AB  - We investigated the role of nonmuscle myosin heavy chain (NMHC) IIB in cultured
      embryonic mouse cardiomyocytes by specific knockdown using RNA interference. NMHC
      IIB protein levels decreased 90% compared with mock-transfected cells by 3 days
      post transfection. NMHC IIB knockdown resulted in a slow decrease in N-RAP
      protein levels over 6 days with no change in N-RAP transcript levels. N-RAP is a
      scaffold for alpha-actinin and actin assembly during myofibrillogenesis, and we
      quantitated myofibril accumulation by morphometric analysis of alpha-actinin
      organization. Between 3 and 6 days, NMHC IIB knockdown was accompanied by the
      abolishment of cardiomyocyte spreading. During this period the rate of myofibril
      accumulation steadily decreased, correlating with the slowly decreasing levels of
      N-RAP. Between 6 and 8 days NMHC IIB and N-RAP protein levels recovered, and
      cardiomyocyte spreading and myofibril accumulation resumed. Inhibition of
      proteasome function using MG132 led to accumulation of excess N-RAP, and the
      secondary decrease in N-RAP that otherwise accompanied NMHC IIB knockdown was
      abolished. The results show that NMHC IIB knockdown led to decreased N-RAP levels
      through proteasome-mediated degradation. Furthermore, these proteins have
      distinct functional roles, with NMHC IIB playing a role in cardiomyocyte
      spreading and N-RAP functioning in myofibril assembly.

PMID- 18615633
TI  - The four-and-a-half-LIM protein 2 (FHL2) is overexpressed in gliomas and
      associated with oncogenic activities.
AB  - Four-and-a-half-LIM protein 2 (FHL2) is a member of FHL protein family, which
      plays a crucial role in regulating gene expression, cell survival, and migration.
      Although its function in oncogenesis appears to be tumor type-specific, its roles
      in glioma formation and development are yet to be elucidated. In the present
      study, we demonstrated that the mRNA level of FHL2 was elevated in both low- and
      high-grade glioma samples. Overexpression of FHL2 stimulated the proliferation,
      anchorage-independent growth, and migration of human glioblastoma cells.
      Conversely, FHL2 knockdown by short hairpin RNA (shRNA-FHL2) inhibited
      glioblastoma cell proliferation and migration. Overexpression of FHL2 increased
      the tumorigenicity of glioblastoma cells in nude mice and decreased the mRNA
      levels of p53 and its downstream proapoptotic genes, including p21, Bcl2
      associated protein X (Bax), and p53-upregulated modulator of apoptosis. It also
      enhanced the promoter activities of activator protein-1 (AP-1), human telomerase
      reverse transcriptase, and survivin genes. Together, these results provide the
      first evidence that FHL2 contributes to glioma carcinogenesis.

PMID- 18615634
TI  - NMR characterization of the host-guest inclusion complex between beta
      cyclodextrin and doxepin.
AB  - The interaction between doxepin, a member of the tricyclic antidepressant (TCA)
      class of drugs, with beta-cyclodextrin (beta-CD) was investigated using NMR.
      Several TCAs have been reported to form a complex with beta-CD having 1:1
      stoichiometry. Previous results from UV-visible spectroscopy, fluorescence
      measurements, and molecular modeling indicated that for imipramine, desipramine,
      and amitriptyline, the TCA aliphatic tail is included in the cyclodextrin cavity
      with apparently no interaction of the tricyclic ring. An alternative view of the
      doxepin-beta-CD complex is presented in this work using analysis of complexation
      induced chemical shifts (CICSs), the method of continuous variation (Job's
      analysis), and analysis of ROESY spectra. The Job's plot derived from the NMR
      spectral data confirms that the complex formed has 1:1 stoichiometry. The largest
      changes in the CICS data were observed for the aromatic protons of one of the
      doxepin rings, with much smaller chemical shift changes observed for the protons
      of the other aromatic ring and the doxepin tail. Perhaps the most significant
      evidence for inclusion of the doxepin tricyclic ring is the strong ROESY cross
      peaks between the doxepin aromatic resonances and the protons located inside the
      beta-CD cavity. Changes in the doxepin (1)H NMR spectrum and the behavior of
      ROESY exchange cross peaks suggest that inclusion complex formation decreases the
      rate of internal motions of doxepin.

PMID- 18615635
TI  - A 3-year analysis of plateletpheresis donor deferral pattern in a tertiary health
      care institute: assessing the current donor selection criteria in Indian
      scenario.
AB  - INTRODUCTION: This study reports the frequency and nature of plateletpheresis
      deferrals and evaluates donors with low platelet count and hemoglobin levels so
      as to assess the possibility of reentry without hampering donor safety. MATERIALS
      AND METHODS: Three-year retrospective data of plateletpheresis deferral was
      collected. Data from actual procedures was also reviewed to analyze the safety of
      performing plateletpheresis in donors with low hemoglobin and platelet values.
      RESULTS: Four hundred sixteen donors were deferred for various reasons among
      1,515 screened (27.5%), of which 69.7% deferrals were because of low platelet
      count (55.8%) and less hemoglobin levels. Among the low platelet count donor
      group, 20.3% had a count between 141 and 149 x 10(9)/L and 41.8% below 120 x
      10(9)/L. Of the 14% donors deferred for low hemoglobin, 62.1% had values in the
      range of 11.5-12.4 g/dL with normal mean corpuscular volume and red cell
      distribution width in most (86.2%) of them. Expected blood loss in each procedure
      varied between 20 and 30 mL, whereas RBC contamination in the product varied from
      0 to 1.6 mL in 538 procedures. There were 176 donations with predonation platelet
      count <180 x 10(9)/L (32.7%). None of the 14 procedures performed on donors with
      platelet count of 150 x 10(9)/L showed evidence of thrombocytopenia or donor
      reaction. CONCLUSION: Lowering the cut-off value for plateletpheresis from 12.5
      g/dL to 11.5 g/dL has no deleterious effect on donor safety as the blood loss is
      minimal. One-fifth deferrals can be reconsidered if the criteria of
      plateletpheresis donor selection are relaxed for hemoglobin and platelet count.

PMID- 18615636
TI  - Morphogenesis and regulation of Bergmann glial processes during Purkinje cell
      dendritic spine ensheathment and synaptogenesis.
AB  - Astrocytes have an important role in synaptic formation and function but how
      astrocytic processes become associated with synaptic structures during
      development is not well understood. Here we analyzed the pattern of growth of the
      processes extending off the main Bergmann glial (BG) shafts during synaptogenesis
      in the cerebellum. We found that during this period, BG process outgrowth was
      correlated with increased ensheathment of dendritic spines. In addition, two
      photon time-lapse imaging revealed that BG processes were highly dynamic, and
      processes became more stable as the period of spine ensheathment progressed.
      While process motility was dependent on actin polymerization, activity of
      cytoskeletal regulators Rac1 and RhoG did not play a role in glial process
      dynamics or density, but was critical for maintaining process length. We extended
      this finding to probe the relationship between process morphology and
      ensheathment, finding that shortened processes result in decreased coverage of
      the spine. Furthermore, we found that areas in which BG expressed dn-Rac1, and
      therefore had a lower level of synaptic ensheathment, showed an overall increase
      in synapse number. These analyses reveal how BG processes grow to surround
      synaptic structures, elucidate the importance of BG process structure for proper
      development of synaptic ensheathment, and reveal a role for ensheathment in
      synapse formation.

PMID- 18615637
TI  - Galectin-3/MAC-2, Ras and PI3K activate complement receptor-3 and scavenger
      receptor-AI/II mediated myelin phagocytosis in microglia.
AB  - The removal of degenerated myelin is essential for repair in Wallerian
      degeneration that follows traumatic injury to axons and in autoimmune
      demyelinating diseases (e.g., multiple sclerosis). Microglia can remove
      degenerated myelin through phosphatidylinositol-3-kinase (PI3K)-dependent
      phagocytosis mediated by complement receptor-3 (CR3/MAC-1) and scavenger receptor
      AI/II (SRAI/II). Paradoxically, these receptors are expressed in microglia after
      injury but myelin is not phagocytosed. Additionally, Galectin-3/MAC-2 is
      expressed in microglia that phagocytose but not in microglia that do not
      phagocytose, suggesting that Galectin-3/MAC-2 is instrumental in activating
      phagocytosis. S-trans, trans-farnesylthiosalicylic (FTS), which inhibits Galectin
      3/MAC-2 dependent activation of PI3K through Ras, inhibited phagocytosis. K-Ras
      GTP levels and PI3K activity increased during normal phagocytosis and decreased
      during FTS-inhibited phagocytosis. Galectin-3/MAC-2, which binds and stabilizes
      active Ras, coimmunoprecipitated with Ras and levels of the coimmunoprecipitate
      increased during normal phagocytosis. A role for Galectin-3/MAC-2 dependent
      activation of PI3K through Ras, mostly K-Ras, is thus suggested. An explanation
      may thus be offered for deficient phagocytosis by microglia that express CR3/MAC
      1 and SRAI/II without Galectin-3/MAC-2 and efficient phagocytosis when CR3/MAC-1
      and SRAI/II are co-expressed with Galectin-3/MAC-2.

PMID- 18615638
TI  - Pyramidal cell responses to gamma-aminobutyric acid differ in type I and type II
      cortical dysplasia.
AB  - Abnormalities in the gamma-aminobutyric acid (GABA)-ergic system could be
      responsible for seizures in cortical dysplasia (CD). We examined responses of
      pyramidal neurons to exogenous application of GABA, as well as alterations of
      GABAergic interneuron number and size in pediatric epilepsy surgery patients with
      non-CD, type I CD, and type II CD pathologies. We used the dissociated cell
      preparation for electrophysiology along with immunohistochemistry to identify
      number and size of GABAergic cells. Pyramidal neurons from type I CD tissue
      showed increased EC(50) and faster kinetics compared with cells from non-CD and
      type II CD tissue. Cytomegalic pyramidal neurons showed increased GABA peak
      currents and decreased peak current densities, longer kinetics, and decreased
      sensitivity to zolpidem and zinc compared with normal pyramidal cells from non-CD
      and type I CD. There were fewer but larger glutamic acid decarboxylase (GAD)
      containing cells in type II CD tissue with cytomegalic neurons compared with non
      CD, type I CD, and type II CD without cytomegalic neurons. In addition, GABA
      transporters (VGAT and GAT-1) showed increased staining surrounding cytomegalic
      neurons in type II CD tissue. These results indicate that there are differences
      in GABA(A) receptor-mediated pyramidal cell responses in type I and type II CD.
      Alterations in zolpidem and zinc sensitivities also suggest that cytomegalic
      neurons have altered GABA(A) receptor subunit composition. These findings support
      the hypothesis that patients with type I and type II CD will respond differently
      to GABA-mediated antiepileptic drugs and that cytomegalic neurons have features
      similar to immature neurons with prolonged GABA(A) receptor open channel times.

PMID- 18615640
TI  - High concentrations of cannabinoids activate apoptosis in human U373MG glioma
      cells.
AB  - Cannabinoids bind to two G-protein-coupled receptors, CB1 and CB2, expressed by
      neurons and cells of the immune system, respectively. Glioma cells (astrocyte
      derived brain tumor cells) express cannabinoid receptors, and numerous in vitro
      and in vivo studies performed in rodents have concluded that apoptosis could be
      induced by cannabinoids in these cells. Whether this also applies to human cells
      is controversial; we, therefore, assessed the effect of cannabinoids on human
      glioma cell viability with the human astrocytoma cell line U373MG. We report here
      that U373MG human glioma cells are sensitive only to high concentrations of
      cannabinoids (>5 microg/ml for Delta(9)-THC). Similar concentrations of the
      compounds promoted a rapid activation of extracellular-regulated kinase and c-Jun
      NH2-terminal kinase, suggesting that cannabinoid receptors are functional in
      U373MG cells. Nevertheless, these kinases are not involved in cannabinoid-induced
      cell death in U373MG cells, insofar as blocking their activation with specific
      inhibitors does not reduce cell death. CB1 is expressed in U373MG cells and is
      involved in cannabinoid-induced cell death, in that blocking its activation with
      a specific antagonist (AM251) almost totally prevented cell death following
      incubation of the cells with Delta(9)-THC. In addition, as already reported, some
      cannabinoids may have modest proproliferative properties in U373MG cells. Human
      U373MG glioma cells are sensitive only to very high, pharmacologically irrelevant
      concentrations of cannabinoids, so it seems unlikely that cannabinoids would
      constitute promising molecules for treating malignant astrocytoma; they do not
      induce glioma cell death at doses that could be applied safely to humans.

PMID- 18615639
TI  - Functional contribution of alpha3L8' to the neuronal nicotinic alpha3 receptor.
AB  - The role of position L8', located in transmembrane domain 1 of the neuronal
      nicotinic alpha3 subunit, was characterized by using two-electrode voltage clamp
      in Xenopus oocytes. Four amino acids (Ala, Ser, Phe, and Tyr) were inserted at
      this conserved position, and the mutant subunit was coexpressed with either wild
      type beta2 or beta4 subunits. These substitutions led to significant alterations
      in the pharmacodynamic parameters of cholinergic agents, resulting in loss of
      function. Ala and Ser substitutions resulted in losses in agonist (ACh, nicotine,
      and DMPP) potency and intrinsic activity at both alpha3beta2 and alpha3beta4
      receptors. Similarly, significant changes in antagonist potency were produced by
      the Ala and Ser substitutions. Phe and Tyr mutations did not alter the receptor's
      EC(50) for ACh or nicotine but reduced the EC(50) for DMPP at both receptors. The
      Phe mutation also reduced the intrinsic activity of all agonists tested at both
      receptors. The Tyr mutation, though, led to a decrease in intrinsic activity for
      all agonists at the alpha3beta2 receptor, yet resulted in no changes for DMPP, a
      decrease for nicotine, and an increase for ACh at the alpha3beta4 receptor. The
      most dramatic changes in the receptor's functional properties were produced by
      substitutions that introduced the largest changes in amino acid volume.
      Additional replacements (Gly, Thr, and Val) suggested an inverse correlation
      between amino acid volume at position alpha3L8' and EC(50) for alpha3beta4
      nAChRs; however, alpha3beta2 nAChRs displayed a nonlinear correlation. These data
      demonstrate that structural alterations at position alpha3L8' could propagate to
      the agonist-binding site.

PMID- 18615641
TI  - Comparative study of the influence of Thy1 deficiency and dietary iron deficiency
      on dopaminergic profiles in the mouse striatum.
AB  - Thy-1, a glycosyl-phosphatidylinositol (GPI)-linked integral membrane protein,
      may play a role in stabilizing synapses. Thy1 was identified in a gene expression
      analysis as iron responsive, and subsequent cell culture and animal models of
      iron deficiency expanded this finding to the protein. The importance of Thy1 in
      influencing neurotransmitter feedback mechanisms led to this study to determine
      the relative effects of Thy1 deficiency and dietary iron deficiency on the
      dopaminergic system in the mouse striatum. The model for this analysis was the
      Thy1 null mutant mouse in the presence or absence of dietary iron deficiency. The
      results revealed significant differences in dopaminergic profiles associated with
      Thy1 and iron deficiency and also a sex effect. For example, both iron deficiency
      and the absence of Thy1 are associated with increased dopamine in both sexes, but
      the dopamine transporter is increased in these experimental groups only in female
      mice. In male mice, the increase in dopamine transporter is found only in the
      Thy1 null mutants. Increases in vesicular monoamine transporter and
      phosphorylated tyrosine hydroxlyase are found only in iron-deficient mice. In
      contrast decreased release of dopamine from synaptosomes is found only in the
      Thy1 null mutant animals. In general, these results indicate that a loss of Thy1
      can influence the dopaminergic profile in the striatum. Furthermore, the results
      reveal consistent differences in the dopaminergic profile in Thy1 knockout mice
      compared with iron-deficient mice, indicating that the effects of iron deficiency
      are not due only to a change in Thy1 expression.

PMID- 18615642
TI  - Okadaic acid increases autophagosomes in rat neurons: implications for
      Alzheimer's disease.
AB  - Autophagosomes are accumulated in Alzheimer's disease (AD), but the regulatory
      pathway of autophagy in AD remains largely unknown. By using electron microscopy,
      Western blotting, and immunocytochemistry, here we show that autophagosomes are
      accumulated in rat neurons by okadaic acid (OA), a protein phosphatase-2A
      inhibitor known to enhance tau phosphorylation, beta-amyloid (Abeta) deposition,
      and neuronal death, which are the pathological hallmarks of AD. Autophagy can be
      generally induced via several distinct pathways, such as inhibition of mTOR or
      activation of beclin-1. Interestingly, OA increased both mTOR and beclin-1
      pathways simultaneously, which suggests that autophagy in OA-treated neurons is
      induced mainly via the beclin-1 pathway, and less so via mTOR inhibition.
      Finally, inhibition of autophagy by 3MA reduced cytotoxicity in OA-treated
      neurons. Our novel findings provide new insights into the pathology of and
      therapeutic intervention for AD.

PMID- 18615643
TI  - Reduced brain injury in CD18-deficient mice after experimental intracerebral
      hemorrhage.
AB  - Many studies have indicated leukocytes are a major contributor to brain injuries
      caused by intracerebral hemorrhage (ICH). Leukocyte-expressed CD18 is important
      for neutrophil-endothelial interactions in the vasculature, and CD18 deficiency
      protects against ischemia-reperfusion injury. We investigated whether CD18
      deficiency provides protection against ICH-induced brain injury. Male wild-type
      (WT) CD18(+/+) mice and CD18(-/-) -knockout mice were used in this study. ICH was
      induced by a collagenase injection. Mortality, neurological function, brain
      edema, and myeloperoxidase (MPO) activity as well as tissue expression of
      nitrotyrosine and MPO were evaluated 24 hr after ICH. We discovered significantly
      reduced brain edema and diminished mortality with a concomitant decrease in MPO
      and nitrotyrosine immunoreactivity in brains of CD18-knockout mice.

PMID- 18615644
TI  - Peripheral nerve regeneration is delayed in neuropilin 2-deficient mice.
AB  - Peripheral nerve transection or crush induces expression of class 3 semaphorins
      by epineurial and perineurial cells at the injury site and of the neuropilins
      neuropilin-1 and neuropilin-2 by Schwann and perineurial cells in the nerve
      segment distal to the injury. Neuropilin-dependent class 3 semaphorin signaling
      guides axons during neural development, but the significance of this signaling
      system for regeneration of adult peripheral nerves is not known. To test the
      hypothesis that neuropilin-2 facilitates peripheral-nerve axonal regeneration, we
      crushed sciatic nerves of adult neuropilin-2-deficient and littermate control
      mice. Axonal regeneration through the crush site and into the distal nerve
      segment, repression by the regenerating axons of Schwann cell p75 neurotrophin
      receptor expression, remyelination of the regenerating axons, and recovery of
      normal gait were all significantly slower in the neuropilin-2-deficient mice than
      in the control mice. Thus, neuropilin-2 facilitates peripheral-nerve axonal
      regeneration.

PMID- 18615645
TI  - Effect of chronic gestational treatment with the adenosine A1 receptor agonist R
      phenylisopropyladenosine on metabotropic glutamate receptors/phospholipase C
      pathway in maternal and fetal brain.
AB  - Pregnant Wistar rats were orally treated with the adenosine receptor agonist R
      phenylisopropyladenosine (R-PIA) throughout the gestational period, and the
      status of the metabotropic glutamate (mGlu) receptor/phospholipase C transduction
      pathway from maternal and fetal brain was analyzed. In mothers' brains,
      radioligand binding assays revealed a significant decrease in the Bmax value,
      without any significant alteration in Kd value. Similar results were observed in
      the steady-state level of mGlu(1) and mGlu(5) receptors assayed by Western blot,
      suggesting that both receptor subtypes were modulated by chronic R-PIA treatment.
      mRNA coding mGlu(1) or mGlu(5) receptors was not altered, suggesting a
      posttranscriptional modulation as a possible mechanism of the loss of mGlu(1) and
      mGlu(5) receptors at the membrane surface. Moreover, phospholipase C stimulated
      by (R,S)-3,5-dihydroxyphenylglycine (DHPG), a selective agonist of group I mGlu
      receptors, was also significantly decreased after R-PIA treatment, suggesting a
      heterologous desensitization of group I mGlu/PLC pathway in maternal brain.
      Western blot and RT-PCR assays showed that neither alphaG(q/11) nor PLCbeta(1)
      was affected by R-PIA treatment. In fetal brain, no significant differences in
      mGlu receptors/PLC transduction pathway were observed after R-PIA treatment.
      These results suggest that chronic R-PIA intake during pregnancy modulates group
      I mGlu receptor signalling pathway in maternal brain, promoting a down-regulation
      of mGlu(1) and mGlu(5) receptors and a heterologous desensitization of the
      mGlu/PLC system.

PMID- 18615646
TI  - A technological platform to optimize combinatorial treatment design and discovery
      for chronic spinal cord injury.
AB  - Chronic spinal cord injury (SCI) is associated with the development of serious
      medical concerns. In fact, it is increasingly well documented that most SCI
      patients who survive the first 24 hr will rapidly develop, within a few months to
      a few years, cardiovascular problems, type II diabetes, muscle wasting,
      osteoporosis, immune deficiencies, and other life-threatening problems. The
      cellular mechanisms underlying these so-called secondary health complications
      remain unclear, and no drug or standard approach has been developed to
      specifically treat these complications. To investigate the cellular and metabolic
      changes associated with chronic SCI and functional recovery, work mainly from our
      laboratory recently has led to the characterization of a mouse model of chronic
      paraplegia. This review reports cellular, systemic, and metabolic changes
      (associated mainly with secondary health complications) occurring within a few
      days to a few weeks after SCI in low-thoracic spinal cord-transected mice. We
      also describe our research platform developed to ease technological transfer and
      to accelerate drug-screening studies in animals. A global understanding of the
      many chronic changes occurring after SCI together with efficient tools and
      approaches for testing new or existing drug candidates is likely to yield the
      design of innovative treatments against secondary complications that combine
      cellular plasticity-modulating agents, locomotor network-activating drugs,
      hormonal therapy, and exercise training.

PMID- 18615647
TI  - Regeneration of nigrostriatal dopaminergic axons after transplantation of
      olfactory ensheathing cells and fibroblasts prevents fibrotic scar formation at
      the lesion site.
AB  - The fibrotic scar formed after central nervous system injury has been considered
      an obstacle to axonal regeneration. The present study was designed to examine
      whether cell transplantation into a damaged central nervous system can reduce
      fibrotic scar formation and promote axonal regeneration. Nigrostriatal
      dopaminergic axons were unilaterally transected in rats and cultures of olfactory
      ensheathing cells (OECs), and olfactory nerve fibroblasts were transplanted into
      the lesion site. In the absence of transplants, few tyrosine hydroxylase
      immunoreactive axons extended across the lesion 2 weeks after the transection.
      Reactive astrocytes increased around the lesion, and a fibrotic scar containing
      type IV collagen deposits developed in the lesion center. The immunoreactivity of
      chondroitin sulfate side chains and core protein of NG2 proteoglycan increased in
      and around the lesion. One and 2 weeks after transection and simultaneous
      transplantation, dopaminergic axons regenerated across the transplanted tissues,
      which consisted of p75-immunoreactive OECs and fibronectin-immunoreactive
      fibroblasts. Reactive astrocytes and chondroitin sulfate immunoreactivity
      increased around the transplants, whereas the deposition of type IV collagen and
      fibrotic scar formation were completely prevented at the lesion site.
      Transplantation of meningeal fibroblasts similarly prevented the formation of the
      fibrotic scar, although its effect on regeneration was less potent than
      transplantation of OECs and olfactory nerve fibroblasts. The present results
      suggest that elimination of the inhibitory fibrotic scar is important for neural
      regeneration.

PMID- 18615650
TI  - Ethanol production from nonsterilized carob pod extract by free and immobilized
      Saccharomyces cerevisiae cells using fed-batch culture.
AB  - The production of ethanol from carob pod extract by free and immobilized
      Saccharomyces cerevisiae cells in batch and fed-batch culture was investigated.
      Fed-batch culture proved to be a better fermentation system for the production of
      ethanol than batch culture. In fed-batch culture, both free and immobilized S.
      cerevisiae cells gave the same maximum concentration (62 g/L) of final ethanol at
      an initial sugar concentration of 300 g/L and F = 167 mL/h. The maximum ethanol
      productivity (4.4 g/L h) was obtained with both free and immobilized cells at a
      substrate concentration of 300 g/L and F = 334 mL/h. In repeated fed-batch
      culture, immobilized S. cerevisiae cells gave a higher overall ethanol
      concentration compared with the free cells. The immobilized S. cerevisiae cells
      in Ca-alginate beads retained their ability to produce ethanol for 10 days. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18615648
TI  - Interaction of mitochondrial respiratory inhibitors and excitotoxins potentiates
      cell death in hippocampal slice cultures.
AB  - The broad-spectrum insecticide rotenone, an inhibitor of complex I of the
      mitochondrial electron transport chain (ETC), gives rise to oxidative stress and
      bioenergetic failure. Pesticides including rotenone have been implicated in human
      neurodegenerative diseases, including Parkinson's disease. Another intensively
      investigated hypothesis of neurodegenerative disease involves the toxic action of
      the excitatory neurotransmitter glutamate. In the present study, we determined
      whether concomitant exposure of rotenone plus tetraethylammonium chloride (TEA)
      or the specific glutamate receptor agonists N-methyl-D-aspartate (NMDA) or alpha
      amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) would cause greater
      cell death in organotypic hippocampal slice cultures than when given separately.
      Low, sublethal rotenone (100 nM), TEA (0.5-2.0 mM), NMDA (1.0-10 microM), and
      AMPA (1.0-10 microM) alone resulted in little cell death as determined by
      propidium iodide fluorescence. However, cell death was significantly to
      dramatically potentiated when the hippocampal slices were coincubated with
      comparable concentrations of rotenone plus TEA, NMDA, or AMPA. Similarly, in the
      presence of 10 microM NMDA, ETC inhibitors blocking other mitochondrial complexes
      also potentiated cell death. Immunohistochemical analysis using glial fibrillary
      acidic protein antibody determined that the cell death was preferentially
      neuronal. These results demonstrate that two different classes of toxicants can
      interact, resulting in potentiation of neurotoxicity, and further suggest that a
      combinatorial therapeutic approach may be required to ameliorate the potentiated
      cell death.

PMID- 18615651
TI  - Scale-up on basis of structured mixing models: A new concept.
AB  - A new scale-up concept based upon mixing models for bioreactors equipped with
      Rushton turbines using the tanks-in-series concept is presented. The physical
      mixing model includes four adjustable parameters, i.e., radial and axial
      circulation time, number of ideally mixed elements in one cascade, and the volume
      of the ideally mixed turbine region. The values of the model parameters were
      adjusted with the application of a modified Monte-Carlo optimization method,
      which fitted the simulated response function to the experimental curve. The
      number of cascade elements turned out to be constant (N = 4). The model parameter
      radial circulation time is in good agreement with the one obtained by the pumping
      capacity. In case of remaining parameters a first or second order formal equation
      was developed, including four operational parameters (stirring and aeration
      intensity, scale, viscosity). This concept can be extended to several other types
      of bioreactors as well, and it seems to be a suitable tool to compare the
      bioprocess performance of different types of bioreactors. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18615652
TI  - Selective protein transport through a thin cellulose coated porous membrane.
AB  - A new composite membrane was designed and studied for permselectivity of various
      molecular weight proteins. The membrane is composed of a porous substrate
      membrane [Durapore; poly(vinylidene fluoride)] coated with a thin dense layer of
      regenerated cellulose. This composite membrane was fabricated by spin coating a
      cellulose acetate solution onto the membrane, followed by alkaline hydrolysis of
      the cellulose acetate coating to regenerate cellulose. The coated layer was
      physically characterized by scanning electron microscopy (SEM) and infrared (IR)
      spectroscopy. In addition, the water uptake into and permeation properties of
      macromolecules across the coated and uncoated membranes were studied. A typical
      composite membrane coating was 0.8 +/- 0.2 mum thick, resulting in a molecular
      weight cutoff of approximately 40,000 daltons. This composite membrane also
      demonstrated negligible diffusional lag time for permeants, due to the
      diffusional barrier. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615653
TI  - EPR characterizations of alpha-chymotrypsin active site dynamics in reversed
      micelles at enhanced gas pressures and after subjection to clathrate formation
      conditions.
AB  - Electron paramagnetic resonance spectroscopy is used to characterize the active
      site dynamics of alpha-chymotrypsin solubilized in reversed micelles. Of
      particular interest is the behavior of the enzyme when the micellar system is
      subjected to enhanced gas pressures and low temperatures. At specific
      thermodynamic conditions, clathrate hydrates from from the intramicellar water,
      reducing the micelle size and water content. Also, beyond a critical pressure,
      micellar instbility results. The EPR spectra under these conditions indicate that
      the rotational correlation times increase appreciably only when the water-to
      surfactant molar ratio, W(0), is reduced to values lower than 10. The EPR
      characterization also reveals a remarkable resilience of the enzyme when
      subjected to pressure-induced changes; when returned to ambient conditions,
      activity and active site dynamics are fully restored. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615654
TI  - Immobilization of a proteinase from the extremely thermophilic organism Thermus
      Rt41A.
AB  - An extracellular proteinase from Thermus strain Rt41A was immobilized to
      controlled pore glass (CPG) beads. The properties of the free and CPG-immobilized
      enzymes were compared using both a large (azocasein) and a small (peptidase)
      substrate. The specific activity of the immobilized proteinase was 5284 azoU/mg
      with azocasein and 144 sucU/mg for SucAAPFpNA. The percentage recovery of enzyme
      activity was unaffected by pore size when it was immobilized at a fixed level of
      activity/g of beads, whereas it increased with increasing pore size when added at
      a fixed level/m(2) of support. Saturation of the CPG beads was observed at 540
      azoU/m(2) of 105-nm beads. Lower levels (50 azoU/m(2) of 50-nm beads) were used
      in characterization experiments. The pH optimum of the immobilized Rt41A
      proteinase was 8.0 for azocasein and 9.5 for SucAAPFpNA, compared with the free
      proteinase which was 10.5 for both substrates. The immobilized enzyme retained
      65% of its maximum activity against azocasein at pH 12, whereas the free
      proteinase retained less than 10% under the same conditions. Stability at 80
      degrees C increased on immobilization at all pH values between 5 and 11, the
      greatest increase in half-life being approximately 12-fold at pH 7.0. Temperature
      activity profiles for both the free and immobilized enzymes were similar for both
      substrates. The stability of the immobilized proteinase, however, was higher than
      that of the free enzyme in the absence and presence of CaCl(2). Overall, the
      results show that low levels of calcium (10 muM) protect against thermal
      denaturation, but that high calcium or immobilization are required to protect
      against autolysis. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615655
TI  - Two-Step biocatalytic conversion of an ester to an aldehyde in reverse micelles.
AB  - Lipases from Candida cyclindracea (L-1754) and wheat germ (L-3001) have been used
      to hydrolyze esters to their corresponding alcohols and acids in reverse
      micelles. Alcohol dehydrogenase from baker's yeast (YADH) was subsequently used
      to reduce the alcohol products to aldehydes. Cofactor recycling in the redox
      reaction was achieved using a sacrificial cosubstrate, as described previously.
      Four surfactants (sodium dioctylsulfosuccinate, Nonidet P-40 with Triton X-35,
      polyoxyethylene, 10-cetyl-ether, polyoxyethylene sorbitan trioleate) were
      employed to determine the effect of amphiphile on ester hydrolysis and redox
      reaction rates separately. The effect of type of organic solvent, W(0)
      [(water]/[surfactant)], and substrate concentration on separte enzyme activity
      were also investigated. A brief investigation of a single phase, two-step
      reaction catalyzed by the combination of lipase and YADH in reverse micelles is
      also reported. The activities of the enzymes are significantly different when
      used together instead of independently. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615656
TI  - Modeling the regulation of bacterial genes producing proteins that strongly
      influence growth.
AB  - A theoretical method for comparing the performance of rival models of bacterial
      genetic regulation is presented. The particukar difficulties involved in
      describing the regulated synthesis of proteins that strongly influence cell
      growth are identiied, and the method is specifically designed to treat such
      cases. The method employs a mathematical description of intrinsic perturbations
      occurring during exponential growth to test the performance of regulatory models.
      Specific models of transcriptional and translational regulation are inserted into
      a general gene-expression framework in order to determine their control
      responses. Applying thhis approach to examine the regulation of RNA polymerase
      synthesis in Eschericia coli provides support for the hypothesis that rpoB
      translation is regulated by cooperative binding of multiple RNA polymerase
      molecules to the mRNA. The framework is of a sufficiently general form that the
      method can be used to study mechanisms involved in controlling synthesis of any
      bacterial protein. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615657
TI  - Continuous culture of Methanococcus jannaschii, an extremely thermophilic
      methanogen.
AB  - Methanococcus jannaschii, an extremely thermophilic methanogen isolated from a
      deep-sea hydrothermal vent, was grown at 80 degrees C in continuous culture on a
      mineral salts medium gassed with H(2) and CO(2) at three different flow rates.
      The maximum specific growth rate was 0.56 h(-1), and the maximum specific methane
      productivity was 0.32 (mol g(-1) h(-1)). Uncoupling of growth and methane
      production was evidenced by an increase in teh non-growth-associated rate of
      methane formation, beta, with increasing gaseous input. The specific hydrogenase
      activity exhibited growth-assiciated behaviour at low growth rates, but showed no
      dependence on growth at higher growth rates. The growth dependence of hydrogenase
      activity is consistent with the pressure dependence of hydrogenase activity
      measured in previous experiments. In contrast, the specific protease activity was
      independent of the growth rate over the entire range of dilution rates studied.
      (c) 1994 John Wiley & Sons, Inc.

PMID- 18615658
TI  - Biosensor for continuos glucose monitoring.
AB  - A potentially implantable glucose biosensor for continuous monitoring of glucose
      levels in diabetic patients has been developed. The glucose biosensor is based on
      an amperometric oxygen electrode and glucose oxidase immobilized on carbon powder
      held in a form of a liquid suspension. The enzyme material can be replaced (the
      sensor recharged) without sensor disassembly. Recharging of the biosensor is
      achieved by injecting fresh immobilized enzyme into the sensor using a septum.
      Diffusion membranes made of silastic latex-rubber coatings over a microporous
      polycarbonate membrane are used. Calibration curves of the amperometric signal
      show linearity over a wide range of glucose concentrations-up to 500 mg/dL (28
      mM), covering hypoglycemic, normoglycemic, and hyperglycemic conditions.
      Preliminary in vitro studies of the biosensor show stable performance during
      several recharge cycles (of 14 days each) over a period of 4 months. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18615659
TI  - The role of weakly polar and H-bonding interactions in the stabilization of the
      conformers of FGG, WGG, and YGG: an aqueous phase computational study.
AB  - The energetics of intramolecular interactions on the conformational potential
      energy surface of the terminally protected N-Ac-Phe-Gly-Gly-NHMe (FGG), N-Ac-Trp
      Gly-Gly-NHMe (WGG), and N-Ac-Tyr-Gly-Gly-NHMe (YGG) tripeptides was investigated.
      To identify the representative conformations, simulated annealing molecular
      dynamics (MD) and density functional theory (DFT) methods were used. The
      interaction energies were calculated at the BHandHLYP/aug-cc-pVTZ level of
      theory. In the global minima, 10%, 31%, and 10% of the stabilization energy come
      from weakly polar interactions, respectively, in FGG, WGG, and YGG. In the
      prominent cases 46%, 62%, and 46% of the stabilization energy is from the weakly
      polar interactions, respectively, in FGG, WGG, and YGG. On average, weakly polar
      interactions account for 15%, 34%, and 9% of the stabilization energies of the
      FGG, WGG, and YGG conformers, respectively. Thus, weakly polar interactions can
      make an important energetic contribution to protein structure and function.

PMID- 18615660
TI  - Nucleic acids absorbance in Mid IR and its effect on diagnostic variates during
      cell division: a case study with lymphoblastic cells.
AB  - The differences in the absorbance in the mid infrared region (Mid IR) between
      normal and abnormal tissues have been shown to be a possible criterion for the
      detection of different forms of cancer. The present work aimed to study the
      effects of cell growth and DNA synthesis on the RNA/DNA ratio, which is a
      promising parameter for cancer diagnosis by inducing synthesis of DNA.
      Lymphoblastic cell lines were synchronized by methotrexate and harvested for
      Fourier transform infrared microscopy (FTIR-MSP) at 30-min interval after
      thymidine addition. The distribution of DNA in the cells/nuclei and variation of
      nuclear size was studied using the fluorescent dye propidium iodide (PI) and the
      nuclear volume was calculated from microscopy. We analyzed the ratio of RNA and
      DNA to quantify the relative amounts during the process by taking the ratios
      I(1121)/I(1020) (symmetric) and the I(1244)/I(1230) (antisymmetric) phosphate
      vibrations. The pattern of changes in the ratios overtime obtained in the
      symmetric and antisymmetric vibrations were similar though the magnitudes were
      different. Only a minor effect on the RNA/DNA ratio (due to nuclear volume
      changes) was observed. The effect due to the unfolding of DNA is greatly masked
      due to RNA absorbance. The effectiveness of this ratio may lie in the increased
      transcriptional levels in carcinogenic tissues rather than changes occurring due
      to unfolding and folding of DNA.

PMID- 18615661
TI  - Investigations of thermotropic phase behavior of newly developed synthetic
      PEGylated lipids using Raman spectro-microscopy.
AB  - In this article, a temperature-controlled Raman spectro-microscopic technique has
      been utilized to detect and analyze the phase behaviors of two newly developed
      synthetic PEGylated lipids trademarked as QuSomes, which spontaneously form
      liposomes upon hydration in contrast to conventional lipids. The amphiphiles
      considered in this study differ in their hydrophobic hydrocarbon chain length and
      contain different units of polyethylene glycol (PEG) hydrophilic headgroups.
      Raman spectra of these new artificial lipids have been recorded in the spectral
      range of 500-3100 cm(-1) by using a Raman microscope system in conjunction with a
      temperature-controlled sample holder. The gel to liquid phase transitions of the
      sample lipids composed of pure 1,2-dimyristoyl-rac-glycerol-3-dodecaethylene
      glycol (GDM-12) and 1,2-distearoyl-rac-glycerol-3-triicosaethylene glycol (GDS
      23) have been revealed by plotting peak intensity ratios in the C-H stretching
      region as a function of temperature. From this study, we have found that the main
      phase transitions occur at a temperature of approximately 5.2 and 21.2 degrees C
      for pure GDM-12 and GDS-23, respectively. Furthermore, the lipid GDS-23 also
      shows a postphase transition temperature at 33.6 degrees C. To verify our
      results, differential scanning calorimetry (DSC) experiments have been conducted
      and the results are found to be in an excellent agreement with Raman scattering
      data. This important information may find application in various studies
      including the development of lipid-based novel substances and drug delivery
      systems.

PMID- 18615662
TI  - Computational analysis of glycoside hydrolase family 1 specificities.
AB  - Glycoside hydrolase family 1 consists of beta-glucosidases, beta-galactosidases,
      6-phospho-beta-galactosidases, myrosinases, and other enzymes having similar
      primary and tertiary structures but diverse specificities. Among these enzymes,
      beta-glucosidases hydrolyze cellobiose to glucose, and therefore they are key
      players in any cellulose to glucose process. All family members attack beta
      glycosidic bonds between a pyranosyl glycon and an aglycon, but most have little
      specificity for the aglycon or for the bond configuration. Furthermore, glycon
      specificity is not absolute. Sixteen family members (six beta-glucosidases, two
      cyanogenic beta-glucosidases, one 6-phospho-beta-galactosidase, two myrosinases,
      and five beta-glycosidases) have known tertiary structures. We have used
      automated docking to computationally bind disaccharides with allopyranosyl,
      galactopyranosyl, glucopyranosyl, mannopyranosyl, 6-phosphogalactopyranosyl, and
      6-phosphoglucopyranosyl glycons, all linked by beta-(1,2), beta-(1,3), beta
      (1,4), and beta-(1,6)-glycosidic bonds to beta-glucopyranoside aglycons, along
      with beta-(1,1-thio)-allopyranosyl, -galactopyranosyl, -glucopyranosyl, and 
      mannopyranosyl) beta-glucopyranosides, into all of these structures to
      investigate the structural determinants of their enzyme specificities. The
      following are the eight active-site residues: Glu191, Thr194, Phe205, Asn285,
      Arg336, Asn376, Trp378, and Trp465 (Zea mays beta-glucosidase numbering), that
      control a significant amount of glycon specificity.

PMID- 18615663
TI  - Advanced bladder cancer: so many drugs, so little progress : what's wrong with
      this picture?

PMID- 18615664
TI  - The power of prediction.

PMID- 18615665
TI  - Can bronchodilator response predict bronchial response to methacholine in
      preschool coughers?
AB  - The aim of the present study was to determine the relationship between
      bronchodilator response, assessed by interrupter resistance (Rint), and bronchial
      reactivity in preschool children with chronic cough. Thirty-eight children
      coughers (median age 5.0 years, range 2.8-6.4) were tested. Bronchodilator
      response was recorded within 4 months before methacholine challenge. Response to
      the latter was assessed using transcutaneous partial pressure of oxygen and Rint.
      Children were considered responders if a 20% fall in transcutaneous partial
      pressure of oxygen occurred during the bronchial challenge. Bronchodilator
      response was not different between responders (n = 24) and nonresponders (n = 14)
      [median (range) -0.11 (-0.44-0.09) vs. -0.08 (-0.21-0.10) kPa L(-1) sec;
      respectively]. However, none of the nonresponders had a bronchodilator response
      larger than -0.21 kPa L(-1) sec, this cutoff had a 100% positive and a 44%
      negative predictive value to predict a positive methacholine challenge. The
      relationship between bronchodilator response and bronchial methacholine
      responsiveness reached the limit of significance (P = 0.048). Furthermore, the
      magnitude of the bronchodilator response was correlated to the level of
      methacholine-induced level of bronchoconstriction (P = 0.01), and to the
      postchallenge bronchodilation (P = 0.04), all values expressed as % predicted.
      Moreover, the postbronchodilator Rint value obtained with preceding methacholine
      challenge was lower than the postbronchodilator value without preceding
      methacholine challenge in 71.4% (10/14) of the nonresponders and in only 33.3%
      (8/24) of the responders. Conclusions in preschool coughers bronchodilator
      response, assessed by the interrupter technique, was correlated to the bronchial
      responsiveness to methacholine. Non responders had a bronchodilator response not
      larger than -0.21 kPa L(-1) sec.

PMID- 18615666
TI  - Percent true calcium absorption, mineral metabolism, and bone mineralization in
      children with cystic fibrosis: effect of supplementation with vitamin D and
      calcium.
AB  - OBJECTIVE: To assess whether percent true calcium absorption (alpha) is normal in
      children with cystic fibrosis (CF) and to assess whether supplementation with
      2,000 IU vitamin D(3), 1 g calcium, or both will alter alpha, mineral metabolism,
      and/or bone mass in children with CF. STUDY DESIGN: Fifteen children ages 7-13
      were randomly assigned to one of four different orders to receive all four 6
      month treatments including placebos. Change in 25-hydroxyvitamin D (25-OHD), 1,25
      dihydroxyvitamin D (1,25(OH)(2)D), PTH, bone turnover markers, and minerals after
      6 months, and bone mineral content (Hologic 1000W) after 9 months was measured.
      alpha was measured by a dual stable isotope method using (48)Ca intravenously and
      (46)Ca orally and measuring (48)Ca, (46)Ca, and (42)Ca in a 24-hr urine using
      High Resolution Inductively Coupled Mass Spectroscopy (HR-ICP-MS). Analysis used
      Wilcoxon Sign Ranks. RESULTS: alpha was in the normal range and did not differ by
      treatment (P 35 +/- 10%, Ca 38 +/- 23%, D 36 +/- 11%, D + Ca 46 +/- 21%). One
      gram calcium did not increase serum or urine calcium. Two thousand IU D(3) did
      not increase 25-OHD or change 1,25(OH)(2)D. Serum and urine minerals, markers of
      bone turnover and bone mineral gains did not differ by treatment. CONCLUSIONS:
      alpha is normal in children with CF. One gram calcium and/or 2,000 IU D(3) does
      not change alpha or increase 25-OHD, serum calcium, or mineralization. Longer
      trials of a significantly higher dose of vitamin D(3) shown to increase serum 25
      OHD are needed to assess effects on mineral metabolism and bone mass accrual.
      However, study of therapeutic options other than calcium and vitamin D should be
      encouraged.

PMID- 18615667
TI  - Effect of secondhand cigarette smoke, RSV bronchiolitis and parental asthma on
      urinary cysteinyl LTE4.
AB  - Cysteinyl leukotrienes promote airway inflammation, bronchoconstriction and mucus
      hypersecretion. Cigarette smoking and respiratory syncytial virus (RSV)
      bronchiolitis are known to increase urinary cysteinyl leukotriene E4 (uLTE4), the
      end product of the cysteinyl leukotriene biosynthetic pathway. We tested the
      following hypotheses: (1) Secondhand smoke (SHS) exposure increases uLTE4 in well
      infants and in those hospitalized for RSV bronchiolitis; (2) Length of hospital
      stay for those with RSV bronchiolitis correlates with uLTE4; and (3) Infants with
      parent(s) with asthma will have higher uLTE4. Parental asthma for infants
      hospitalized with RSV bronchiolitis (n = 79) and Well babies (n = 31) was
      determined by questionnaire. Urine was analyzed for LTE4, cotinine, and
      creatinine. SHS exposure was determined by cotinine to creatinine ratio. Chi
      square, or t-tests were used to determine significant differences between two
      groups. A three-way analysis of variance compared the effects of SHS exposure and
      parental asthma on uLTE4 in Well versus RSV babies. Independent variables
      predicting length of hospital stay were determined by stepwise multiple
      regression. High SHS exposure and RSV significantly increased uLTE4. The SHS
      induced increase in uLTE4 was seen in infants with no parental asthma but not in
      those with parental asthma. Length of hospital stay positively correlated with
      uLTE4. We concluded that SHS exposure may increase the severity of bronchiolitis
      in RSV-infected infants by enhancing production of cysLTs in infants with no
      parental asthma.

PMID- 18615668
TI  - Pediatric inflammatory myofibroblastic tumor of the trachea: a case report and
      review of the literature.
AB  - Inflammatory myofibroblastic tumors (IMTs) are relatively rare entities of a
      distinct histologic appearance and benign clinical course. Although these lesions
      have been described in virtually every anatomic location, there are few
      documented reports with tracheal localization. We add to the short list of
      pediatric IMTs of the trachea, a 13-year-old boy that was referred to our
      pediatric respiratory unit for evaluation of his respiratory distress. In
      particular, we describe the clinical and pathologic features of this patient and
      present a review of all reported lesions in the available literature.

PMID- 18615669
TI  - Socioeconomic factors and asthma control in children.
AB  - OBJECTIVES: The objective of this study was to evaluate the association between
      socioeconomic factors and asthma control in children, as defined by the Canadian
      Pediatric Asthma Consensus Guidelines. PATIENTS AND METHODS: Cross-sectional data
      from a completed study of 879 asthmatic children between the ages of 1 and 18
      residing in the Greater Toronto Area were used. The database included data on
      demographics, health status, asthma control, and health-related quality of life.
      Stepwise forward modeling multiple regression was used to investigate the impact
      of socioeconomic status on asthma control, based on six control parameters from
      the 2003 Canadian Pediatric Asthma Consensus Guidelines. RESULTS: Only 11% of
      patients met the requirements for acceptable control, while 20% had intermediate
      control, and 69% had unacceptable asthma control. Children from families in lower
      income adequacy levels had poorer control. CONCLUSIONS: Disparities in asthma
      control between children from families of different socio-economic strata
      persist, even with adjustment for utilization of primary care services and use of
      controller medications.

PMID- 18615670
TI  - Effects of betamethasone on peripheral arterial development in term fetal rabbit.
AB  - Glucocorticoids are given antenatally to promote pulmonary epithelial maturation
      and prevent respiratory distress syndrome in premature newborns. In contrast to
      airway changes, effects on vessels are less documented. We hypothesized that
      antenatal betamethasone (BM) administration promotes vascular development. Does
      received either a course of BM = 0.05 mg/kg/day (18 does, 70 fetuses), BM = 0.1
      mg/kg/day (20 does, 75 fetuses), or saline (11 does, 92 fetuses) starting on d25,
      26 (canalicular stage), d27, d28 (saccular stage), and d29 (alveolar stage) of
      gestation. In total 236 fetuses from 49 does were examined at term (d31) in terms
      of vascular development. Lung specimens were weighed and formalin fixed for
      morphometry. We determined differences in fetal body, liver and lung weight,
      proportionate medial thickness, muscularization of intra-acinar vessels, number
      of vessels under 100 microm, as well as immunoreactivity to Flk-1 in vascular
      smooth muscle and endothelial cells. A dose-dependent reduction in neonatal body
      and organ weight was observed in fetuses exposed to BM at d25. In contrast, term
      liver weight increased after late administration of BM (d28, 29). There was a
      dose- and time-dependent thinning of the pulmonary arterial media, which
      coincided with a decreased proportion of intra- and pre-acinar muscularized
      arteries (ED <or= 60 microm) and increased microvascularization (ED <or= 30), as
      well as increased endothelial immunoreactivity for Flk-1. Analyzing our data
      using a purpose designed geometrical model, the results suggest that maternal
      administration of BM promotes changes in vascular morphology, which may be
      compatible with remodeling and vessel formation.

PMID- 18615672
TI  - A 67-year-old male with hypercalcemia and an unrevealing splenectomy.

PMID- 18615671
TI  - Extremely slow methotrexate elimination in a patient with t(9;22) positive acute
      lymphoblastic leukemia treated with imatinib.

PMID- 18615673
TI  - Detection of microembolic signals using power M-mode Doppler sonography in acute
      stroke patients with intracranial artery stenosis.
AB  - PURPOSE: Microembolic signals (MES) can be detected in a variety of clinical
      situations using conventional transcranial Doppler (TCD) sonography. We studied
      the prevalence of positive MESs in acute stroke patients with intracranial artery
      stenosis using power M-mode Doppler (PMD) sonography and also tested the
      feasibility of this new technique. METHOD: Thirty-three consecutive acute
      ischemic stroke or transient ischemic attack patients with intracranial large
      artery occlusive disease were enrolled. PMD/TCD monitoring for 30 minutes was
      used for MES detection downstream of the stenotic artery within 1 week after
      stroke onset. Clinical risk factors in emboli-positive and emboli-negative
      patients were assessed. RESULTS: MESs were detected in 21% (7/33) of patients. No
      significant differences were found in clinical risk factors between emboli
      positive and emboli-negative patients. CONCLUSION: PMD sonography to detect MESs
      in acute stroke patients is feasible and may be used in future clinical trials
      regarding MES detection.

PMID- 18615674
TI  - Prenatal diagnosis of ectopic intrathoracic kidney in a fetus with a left
      diaphragmatic hernia.
AB  - Intrathoracic renal ectopia as a result of a congenital diaphragmatic hernia
      (CDH) is a rare congenital anomaly. We present a case in which the prenatal
      diagnosis of an ectopic intrathoracic kidney was made on routine anatomical
      survey at 28 weeks' gestation. Color doppler sonography imaging revealed the
      renal artery coursing into the infant's thorax and was consistent with CDH, but
      fetal MRI suggested an intact diaphragm. However, neonatal evaluation confirmed
      the diagnosis of intrathoracic kidney with posterior CDH, which was repaired
      without complication. In contrast to diaphragmatic hernia with liver or bowel
      herniation, infants with intrathoracic ectopic kidneys generally do well.

PMID- 18615675
TI  - High-resolution molecular cytogenetic analysis of Wilms tumors highlights
      diagnostic difficulties among small round cell kidney tumors.
AB  - Many solid tumors exhibit characteristic gene fusions, which are reflected by
      balanced translocations at the cytogenetic level. These changes might be useful
      diagnostic and prognostic tools. In Wilms tumor (WT, nephroblastoma) no fusions
      genes or recurrent balanced translocations have been described thus far. To
      screen for cryptic balanced translocations, we have analyzed 17 renal neoplasms,
      histopathologically classified as WT, by a combination of G-banding, multicolor
      FISH, and subtelomeric FISH. This approach revealed several submicroscopic
      chromosomal aberrations and three different seemingly balanced translocations,
      resulting in a heterozygous deletion of HACE1, an EWSR1/ERG fusion, and an
      EWSR1/FLI1 fusion, respectively. As EWSR1 rearrangements are known to be a
      characteristic of Ewing tumors (ET), our findings illustrate the diagnostic
      problems regarding small cell kidney tumors and strongly argue for the need of
      adjuvant diagnostic techniques in this group of neoplasms. In summary, our
      genomic screening approach proved efficient in finding structural chromosomal
      aberrations. The fact that no recurrent translocations were found in the WTs of
      this study argues against the presence of a frequent pathognomonic translocation
      in this disease entity.

PMID- 18615676
TI  - Permeability changes of the cell-contained microcapsules visualized by confocal
      laser scanning microscope.
AB  - Microencapsulation of recombinant cells is a novel means for gene therapy.
      However, one of the major concerns is the relationship between the permeability
      of microcapsule and cell growth. Many studies have focused on the permeability of
      empty microcapsule, but little is known about the effect of the cell growth on
      the permeability of a cell-contained microcapsule. A combination of fluorescence
      labeled protein and confocal laser scanning microscope (CLSM) provides the
      information about the permeability changes during the cell growth. A decrease of
      membrane permeability was detected on the 14th day. Meanwhile, membrane surface
      protein fouling was also investigated. A significant increase of membrane surface
      protein content was detected on the 21st day. In order to study the effect of the
      permeability changes on the cell viability, the membrane of cell-contained
      microcapsules with different permeability was set up by incubating gel beads in
      poly-L-lysine for 5 and 30 min, respectively, to mimic the bovine serum albumin
      cutoff, and a retard of cell growth was found in 7 days' culture. These results
      showed that the protein fouling of the microcapsule membrane caused by the cell
      growth may be an important factor to influence cell viability.

PMID- 18615677
TI  - Stably transfected common fragile site sequences exhibit instability at ectopic
      sites.
AB  - Common fragile sites (CFSs) are loci that are especially prone to forming gaps
      and breaks on metaphase chromosomes under conditions of replication stress.
      Although much has been learned about the cellular responses to gaps and breaks at
      CFSs, less is known about what makes these sites inherently unstable. CFS
      sequences are highly conserved in mammalian evolution and contain a number of
      sequence motifs that are hypothesized to contribute to their instability. To
      examine the role of CFS sequences in chromosome breakage, we stably transfected
      two BACs containing FRA3B sequences and two nonCFS control BACs containing
      similar sequence content into HCT116 cells and isolated cell clones with BACs
      integrated at ectopic sites. Integrated BACs were present at just a few to
      several hundred contiguous copies. Cell clones containing integrated FRA3B BACs
      showed a significant, three to sevenfold increase in aphidicolin-induced gaps and
      breaks at the integration site as compared to control BACs. Furthermore, many
      FRA3B integration sites displayed additional chromosome rearrangements associated
      with CFS instability. Clones were examined for replication timing and it was
      found that the integrated FRA3B sequences were not dependent on late replication
      for their fragility. This is the first direct evidence in human cells that
      introduction of CFS sequences into ectopic nonfragile loci is sufficient to
      recapitulate the instability found at CFSs. These data support the hypothesis
      that sequences at CFSs are inherently unstable, and are a major factor in the
      formation of replication stress induced gaps and breaks at CFSs.

PMID- 18615678
TI  - Comprehensive analysis of 20q13 genes in ovarian cancer identifies ADRM1 as
      amplification target.
AB  - Approximately 25,000 ovarian cancers are diagnosed in the US annually, and 75% of
      cases are in the advanced stage when they are largely incurable. There is a
      critical need for improved early detection tools and development of novel
      treatments. Because chromosome band 20q13 is a commonly DNA amplified region in
      ovarian cancer and increase in 20q13 copy number may be an early event, we
      examined the DNA amplification and RNA expression pattern of 239 microarray
      probes mapping to this region with the goal of identifying gene(s) associated
      with ovarian cancer. Using Agilent expression microarray analysis and FISH to
      tumor tissue arrays, we narrowed the candidates to 19 genes that were
      consistently overexpressed in a subset of tumors amplified for both ZNF217 and
      TPD54, although, interestingly the candidates do not include these two amplified
      genes. Unsupervised clustering of 225 ovarian samples with respect to RNA
      expression of these 19 genes allowed identification of a 20q-amplified subset of
      51 (23%) tumors and this subset was significantly correlated with poor outcome.
      Of the 19 candidate genes in this subset, ADRM1 overexpression was the most
      highly correlated with amplification, was amplified in a higher percentage of
      tumors than ZNF217 and TPD54, and was significantly upregulated with respect to
      stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlates
      significantly with shorter time to recurrence and overall survival. Functional
      analysis is now warranted to determine whether ADRM1 is a target for early
      screening and/or therapy for ovarian cancer.

PMID- 18615679
TI  - Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant
      gastrointestinal stromal tumors.
AB  - BRAF and NRAS are commonly mutated in cancer and represent the most frequent
      genetic events in malignant melanoma. More recently, a subset of melanomas was
      shown to overexpress KIT and harbor KIT mutations. Although most gastrointestinal
      stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA,
      about 10% of the cases lack mutations in these genes. It is our hypothesis
      following the melanoma model that mutations in BRAF or NRAS may play a role in
      wild-type GIST pathogenesis. Alterations in RAS/MEK/ERK pathway may also be
      involved in development of imatinib resistance in GIST, particularly in tumors
      lacking secondary KIT or PDGFRA mutations. Imatinib-naive wild-type GISTs from 61
      patients, including 15 children and 28 imatinib-resistant tumors without
      secondary KIT mutations were analyzed. Screening for hot spots mutations in BRAF
      (exons 11 and 15) and NRAS (exons 2 and 3) was performed. A BRAF exon 15 V600E
      was identified in 3 of 61 GIST patients, who shared similar clinical features,
      being 49- to 55-years-old females and having their tumors located in the small
      bowel. The tumors were strongly KIT immunoreactive and had a high risk of
      malignancy. An identical V600E BRAF mutation was also identified in one of 28
      imatinib resistant GIST lacking a defined mechanism of drug resistance. In
      conclusion, we identified a primary BRAF V600E mutations in 7% of adult GIST
      patients, lacking KIT/PDGFRA mutations. The BRAF-mutated GISTs show predilection
      for small bowel location and high risk of malignancy. A secondary V600E BRAF
      mutation could represent an alternative mechanism of imatinib resistance. Kinase
      inhibitors targeting BRAF may be effective therapeutic options in this molecular
      GIST subset.

PMID- 18615681
TI  - Chronic phase of ETV6-ABL1 positive CML responds to imatinib.

PMID- 18615680
TI  - The MLH1 -93 G>A promoter polymorphism and genetic and epigenetic alterations in
      colon cancer.
AB  - The MLH1 -93 G>A promoter polymorphism has been reported to be associated with an
      increased risk of microsatellite unstable colorectal cancer. Other than
      microsatellite instability, however, the genetic and most epigenetic changes of
      tumors associated with this polymorphism have not been studied. We evaluated
      associations between the -93 G>A polymorphism and CpG island methylator phenotype
      (CIMP), BRAF V600E mutations, and MLH1 methylation in tumors from a sample of
      1,211 individuals with colon cancer and 1,968 controls from Utah, Northern
      California, and Minnesota. The -93 G>A polymorphism was determined by the five
      prime nuclease assay. CIMP was determined previously by methylation-specific PCR
      of CpG islands in MLH1, methylated in tumors (MINT)1, MINT2, MINT31, and CDKN2A
      (p16). The BRAF V600E mutation was determined by sequencing exon 15. The MLH1 -93
      G>A promoter polymorphism was associated with CIMP (odds ratio (OR) 3.44, 95%
      confidence interval (CI) 1.85, 6.42), MLH1 methylation (OR 4.16, 95%CI 2.20,
      7.86), BRAF mutations (OR 4.26, 95%CI 1.83, 9.91), and older age at diagnosis (OR
      3.65, 95%CI 2.08, 6.39) in microsatellite unstable tumors. These associations
      were not observed in stable tumors. Increased age at diagnosis and tumor
      characteristics of microsatellite unstable tumors associated with MLH1 -93 G>A
      suggests the polymorphism is acting at a relatively late stage of colorectal
      carcinogenesis to drive CIMP+ tumors down the microsatellite instability pathway.

PMID- 18615682
TI  - Chronic myeloproliferative disorder with t(8;22)(p11;q11) can mime clonal
      cytogenetic evolution of authentic chronic myelogeneous leukemia.

PMID- 18615683
TI  - Comparison of new bone formation, implant integration, and biocompatibility
      between RGD-hydroxyapatite and pure hydroxyapatite coating for cementless joint
      prostheses--an experimental study in rabbits.
AB  - This is the first work to report on additional Arginin-Glycin-Aspartat (RGD)
      coating on precoated hydroxyapatite (HA) surfaces regarding new bone formation,
      implant bone contact, and biocompatibility compared to pure HA coating and
      uncoated stainless K-wires. There were 39 rabbits in total with 6 animals for the
      RGD-HA and HA group for the 4 week time period and 9 animals for each of the 3
      implant groups for the 12 week observation. A 2.0 K-wire either with RGD-HA or
      with pure HA coating or uncoated was placed into the intramedullary canal of the
      tibia. After 4 and 12 weeks, the tibiae were harvested and three different areas
      of the tibia were assessed for quantitative and qualitative histology for new
      bone formation, direct implant bone contact, and formation of multinucleated
      giant cells. Both RGD-HA and pure HA coating showed statistically higher new bone
      formation and implant bone contact after 12 weeks than the uncoated K-wire. There
      were no significant differences between the RGD-HA and the pure HA coating in new
      bone formation and direct implant bone contact after 4 and 12 weeks. The number
      of multinucleated giant did not differ significantly between the RGD-HA and HA
      group after both time points. Overall, no significant effects of an additional
      RGD coating on HA surfaces were detected in this model after 12 weeks.

PMID- 18615684
TI  - Combining a symptoms index with CA 125 to improve detection of ovarian cancer.
AB  - BACKGROUND: The current study sought to examine whether an index based on the
      specific pattern of symptoms commonly reported by women with ovarian cancer could
      be used in combination with CA 125 to improve the sensitivity or specificity of
      experimental methods of screening for ovarian cancer. METHODS: A prospective case
      control study design was used. Participants included 254 healthy women at high
      risk for disease because of family history, and 75 women with ovarian cancer.
      Logistic regression analysis was used to determine whether the symptom index
      predicted cancer. RESULTS: Symptom index information was found to make a
      significant independent contribution to the prediction of ovarian cancer after
      controlling for CA 125 levels (P<.05). The combination of CA 125 and the symptom
      index identified 89.3% of the women with cancer, 80.6% of the early-stage
      cancers, and 95.1% of the late-stage cancers. The symptom index identified cancer
      in 50% of the affected women who did not have elevated CA 125 levels.
      Unfortunately, 11.8% of the high-risk women without cancer also received a
      positive symptom index score. CONCLUSIONS: The addition of a symptom index to CA
      125 created a composite index with a greater sensitivity for the detection of
      ovarian cancer than CA 125 alone and identified >80% of women with early-stage
      disease. A composite marker such as this could serve as a first screen in a
      multistep screening program in which false-positive findings are identified via
      transvaginal sonography before referral for surgery, leading to an adequate
      positive predictive value for the multistep program.

PMID- 18615685
TI  - Quantification of microvessels in canine lymph nodes.
AB  - Quantification of microvessels in tumors is mostly based on counts of vessel
      profiles in tumor hot spots. Drawbacks of this method include low reproducibility
      and large interobserver variance, mainly as a result of individual differences in
      sampling of image fields for analysis. Our aim was to test an unbiased method for
      quantifying microvessels in healthy and tumorous lymph nodes of dogs. The
      endothelium of blood vessels was detected in paraffin sections by a combination
      of immunohistochemistry (von Willebrand factor) and lectin histochemistry (wheat
      germ agglutinin) in comparison with detection of basal laminae by laminin
      immunohistochemistry or silver impregnation. Systematic uniform random sampling
      of 50 image fields was performed during photo-documentation. An unbiased counting
      frame (area 113,600 microm(2)) was applied to each micrograph. The total area
      sampled from each node was 5.68 mm(2). Vessel profiles were counted according to
      stereological counting rules. Inter- and intraobserver variabilities were tested.
      The application of systematic uniform random sampling was compared with the
      counting of vessel profiles in hot spots. The unbiased estimate of the number of
      vessel profiles per unit area ranged from 100.5 +/- 44.0/mm(2) to 442.6 +/-
      102.5/mm(2) in contrast to 264 +/- 72.2/mm(2) to 771.0 +/- 108.2/mm(2) in hot
      spots. The advantage of using systematic uniform random sampling is its
      reproducibility, with reasonable interobserver and low intraobserver variance.
      This method also allows for the possibility of using archival material, because
      staining quality is not limiting as it is for image analysis, and artifacts can
      easily be excluded. However, this method is comparatively time-consuming.

PMID- 18615687
TI  - Quantitative analysis and localization of mRNA transcripts of type I collagen,
      osteocalcin, MMP 2, MMP 8, and MMP 13 during bone healing in a rat calvarial
      experimental defect model.
AB  - The study examined the expression of matrix metalloproteinases (MMPs), type I
      collagen and osteocalcin during bone healing in a rat calvarial experimental
      defect model. Twelve-week-old male Wistar rats were used. A full-thickness
      standardized trephine defect was made in the parietal bone, with the rat under
      anesthesia. RNA was extracted from tissue that filled the original bone defect on
      days 1 and 3 and in weeks 1, 2, 3, 5, 8, 10, 12, 18, and 24 and processed for
      quantitative analysis of expression of type I collagen, osteocalcin and matrix
      metalloproteinases (MMPs) 2, 8, and 13 by using real-time polymerase chain
      reaction. Alternatively, the rats were fixed by perfusion through the aorta and
      resected calvaria were processed for in situ hybridization for these molecules.
      The expression of type I collagen, osteocalcin and MMPs 2 and 13 increased toward
      week 2 and decreased thereafter, whereas the expression of MMP 8 was the highest
      on day 1. The mRNA transcripts of type I collagen and osteocalcin were localized
      in osteoblasts and osteocytes, some of which expressed MMPs 2, 8, and 13.
      Osteoblasts and osteocytes may play a role in the remodeling of extracellular
      matrices with MMPs during healing of a defect in bone.

PMID- 18615689
TI  - Kinetic analysis of microbial sulfate reduction by desulfovibrio desulfuricans in
      an anaerobic upflow porous media biofilm reactor.
AB  - An anaerobic upflow porous media biofilm reactor was designed to study the
      kinetics and stoichiometry of hydrogen sulfide production by the sulfate-reducing
      bacterium (SRB) Desulfovibrio desulfuricans (ATCC 5575) as the first step for the
      modeling and control of formation souring (H(2)S) in oil field porous media. The
      reactor was a packed bed (50 x 5.5 cm) tubular reactor. Sea sand (140 to 375 mum)
      was used as the porous media. The initial indication of souring was the
      appearance of well-separated black spots (precipitates of iron sulfide) in the
      sand bed. The blackened zones expanded radially and upward through the column.
      New spots also appeared and expanded into the cone shapes. Lactate (substrate)
      was depleted and hydrogen sulfide appeared in the effluent.Analysis of the pseudo
      steady state column shows that there were concentration gradients for lactate and
      hydrogen sulfide along the column. The results indicate that most of the lactate
      was consumed at the front part of the column. Measurements of SRB biomass on the
      solid phase (sand) and in the liquid phase indicate that the maximum
      concentration of SRB biomass resided at the front part of the column while the
      maximum in the liquid phase occurred further downstream. The stoichiometry
      regarding lactate consumption and hydrogen sulfide production observed in the
      porous media reactor was different from that in a chemostat. After analyzing the
      radial dispersion coefficient for the SRB in porous media and kinetics of
      microbial growth, it was deduced that transport phenomena dominate the souring
      process in our porous media reactor system. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615690
TI  - Predictions for oxygen supply control to enhance population stability of
      engineered production strains.
AB  - The simultaneous growth and product formation in a microbial culture is an
      important feature of several laboratory, industrial, and environmental
      bioprocesses. Metabolic burden associated with product formation in these
      bioprocesses may lead to growth advantage of a nonproducing mutant leading to a
      loss of the producing population over time. A simple population dynamics model
      demonstrates the extreme sensitivity of population stability to the engineered
      productivity of a strain. Here we use flux balance analysis to estimate the
      effects of the metabolic burden associated with product secretion on optimal
      growth rates. Comparing the optimal growth rates of the producing and
      nonproducing strains under a given processing condition allows us to predict the
      population stability. In order to increase stability of an engineered strain, we
      determine processing conditions that simultaneously maximize the growth rate of
      the producing population while minimizing the growth rate of a nonproducing
      population. Using valine, tryptophan, and lysine production as specific examples,
      we demonstrate that although an appropriate choice of oxygenation may increase
      culture longevity more than twofold, total production as governed by economic
      criterion can be increased by several orders of magnitude. Choice of optimal
      nutrient and oxygen supply rates to enhance stability is important both for
      strain screening as well as for culture of engineered strains. Appropriate design
      of the culture environment can thus be used to enhance the productivity of
      bioprocesses that use engineered production strains. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615691
TI  - Screening of concanavalin A-bead cellulose conjugates using an enzyme thermistor
      with immobilized invertase as the reporter catalyst.
AB  - Screening and design of immobilized biocatalysts (IMBs) is a time-consuming
      process. An ideal process should be universal, fast, convenient, precise, and
      reproducible. Many of these requirements are met by enzymic flow
      microcalorimeters, also known as enzyme thermistors (ETs) or thermal assay probes
      (TAPs). Adaptation of ETs to real measurements of reaction rates requires
      coupling of the mathematical description of the reaction-diffusion phenomena in
      the ET column with heat balance and, subsequently, experimental verification of
      the mathematical model. This article presents such a process developed as an
      adaptation of ETs for the characterization of the microkinetic properties of IMBs
      and their further application for screening of IMBs. The IMBs characterized were
      the preparations of invertase, biospecificaly adsorbed on concanavalin A
      conjugated to activated bead cellulose. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615692
TI  - Modeling hexavalent chromium reduction in Escherichia coli 33456.
AB  - A model based on te analysis of the mechanism of enzymatic reactions was
      developed to characterize the rate and extent of microbial reduction of
      hexavalent chromium in Escherichia coli 33456. A finite reduction capacity (R(c))
      was proposed and incorporated into the enzymatic model to regulate the toxicity
      effect on cells due to the oxidizing power of Cr(VI). The parameter values were
      determined by nonlinear least-square analysis using experimental data of
      anaerobic cultures. The obtained parameters were then used to predict Cr(VI)
      reduction in aerobic cultures along with a modification term of uncompetitive
      inhibition from molecular oxygen. The applicability of the developed model was
      demonstrated through excellent prediction of the results of batch studies
      conducted over range of initial Cr(VI) concentrations, initial cell densities,
      and DO levels. A sensitivity analysis revealed that the parameters obtained using
      the experimental data were unique, and neither change in K(c), the half-velocity
      constant, at high initial Cr(VI) concentrations nor change in R(c), the reduction
      capacity, at low initial Cr(VI) concentrations was sensitive to model prediction.
      (c) 1994 John Wiley & Sons, Inc.

PMID- 18615693
TI  - Surfactant pretreatment of a polysulfone ultrafilter for reduction of antifoam
      fouling.
AB  - Effectiveness of surfactant precoat treatment of the polysulfone ultrafilter was
      first investigated for reduction of membrane fouling in ultrafiltration of
      antifoam. Fifteen different surfactants, including alcohols and synthetic
      nonionic surfactants, were tested. In general, pretreatment with nonionic
      surfactant gave a larger flux than that with alcohol did. The flux increase by
      pretreatment with nonionic surfactant depended on a hydrophile lipophile balance
      (HLB) value and type of hydrophobic tail. The most effective surfactant for
      reducing antifoam fouling among the 15 surfactants was Brij-58 which has an HLB
      value of 16 and a straight alkyl hydrophobic chain. The ultrafiltration flux of
      the membrane treated with Brij-58 was almost three times larger than that of
      untreated membrane. The precoat treatment with Brij-58 was the most effective for
      reducing antifoam fouling in terms of rejection properties.Furthermore, flux was
      also improved by the surfactant pretreatment in ultrafiltration of model process
      streams, such as fermentation media, broth, and yeast suspension with or without
      antifoam. The surfactant Brij-58 was found to be more effective for reducing
      membrane fouling in ultrafiltration of model stream YG compared with ethanol or
      Brij-35. The mean flux increase by the pretreatment with Brij-58 was about 80% in
      ultrafiltration of the model stream without antifoam. When antifoam was added to
      the model stream, flux was almost doubled by the pretreatment with Brij-58. The
      effectiveness of surfactant precoat treatment for reducing membrane fouling was
      also confirmed in terms of rejection properties. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615694
TI  - Separation of penicillin G from phenylacetic acid in a supported liquid membrane
      system.
AB  - The separation of penicillin G (Pen G) from phenylacetic acid (PAA) by use of a
      supported liquid membrane (SLM) system with Amberlite LA-2 dissolved in 1
      decanol, supported on a microporous polypropylene membrane, was studied. The
      results show that the individual permeability of each component in mixture was
      lower than that in a single compartment system and, it suggests a strong
      transport competition between Pen G and PAA. The SLM system in this study proved
      to be a promising process for the selective separation of Pen G from PAA. The
      maximum separation factor was found to be 1.8 under a liquid membrane resistance
      controlled mechanism. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615695
TI  - Optimization of an industrial microalgae fermentation.
AB  - Optimization of cellular productivity of an industrial microalgae fermentation
      was investigated. The fermentation was carried out at Coors Biotech Products
      Company, Fort Collins, Colorado. A mathematical model was developed based on the
      data collected from pilot plant test runs at different operating conditions.
      Pontryagin's maximum principle was used for determining the optimal feed policy.
      A feedback control algorithm was also studied for maximizing the cellular
      productivity. During continuous operation, the optimum dilution rate was
      determined by an adaptive optimization scheme based on the steepest descent
      technique and a recursive least squares estimation of model parameters. A direct
      search algorithm was also applied to determine the optimum feed rate. Comparison
      of the theoretical results of the different optimization schemes revealed that
      the direct search algorithm was preferable because of its simplicity. The
      experimental results of real time application of the feedback algorithm agreed
      fairly well with those of the theoretical analyses. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615696
TI  - Novel protein a affinity matrix prepared from two-dimensional protein crystals.
AB  - In this article, we describe a novel type of affinity matrix which was prepared
      by covalently binding Protein A to crystalline cell surface layers (S-layers)
      from the gram-positive Clostridium thermohydrosulfuricum L111-69. S-layers were
      used in the form of cell wall fragments, which were obtained by breaking whole
      cells by ultrasonification and removing the cell content and the plasma membrane.
      In these thimble shaped structures, revealing a size of 1 to 2 mum, the
      peptidoglycan-containing layer was covered on both faces with a hexagonally
      ordered S-layer lattice composed of identical glycoprotein subunits. After
      crosslinking the S-layer protein with glutaraldehyde, carboxyl groups from acidic
      amino acids were activated with carbodiimide and used for immobilization of
      Protein A. Quantitative determination confirmed that up to two Protein A
      molecules were bound per S-layer subunit leading to a dense monomolecular
      coverage of the immobilization matrix with the ligand.Affinity microparticles
      were capable of adsorbing lgG from solutions of purified preparations, from
      artificial lgG-albumin mixtures, and from serum. The amount of lgG bound to
      affinity microparticles corresponded to the theoretical saturation capacity.
      Under appropriate conditions, up to 95% of the adsorbed lgG could be eluted
      again. Affinity microparticles were found to have an extremely low Protein A
      leakage and a high stability toward mechanical forces. Because pores in the S
      layer lattice revealed a size of 4 to 5 nm, immobilization of Protein A and
      adsorption of lgG was restricted to the outermost surface area. This excludes
      mass transfer problems usually encountered with affinity matrices prepared from
      amorphous polymers where more than 90% of the ligands are immobilized in the
      interior. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615697
TI  - Inactivation of enzymes by organic solvents: New technique with well-defined
      interfacial area.
AB  - A liquid-liquid bubble column apparatus allows exposure of enzyme solutions to
      water-immiscible organic solvents with a known total interfacial area and
      welldefined time scales and flow. It allows clear distinction of the different
      classes of inactivation mechanism. With urease as a model enzyme, octan-2-one and
      butylbenzene act only through the effects of solvent molecules dissolved in the
      aqueous phase, giving first-order inactivation at 0.34 and 0.21 h(-1),
      respectively. Hexane and tridecane act only through exposure to the interface.
      The amount of urease inactivated is proportional to the total area of interface
      exposed, rather than to elapsed time, and may be characterized by a rate of about
      0.5 mukat m(-2). This is consistent with the formation and (partial) inactivation
      of a complete adsorbed monolayer of protein. With butan-1-ol, both mechanisms
      contribute significantly to the observed inactivation. The presence of O(2)
      increases the rate of interfacial inactivation, but not that by dissolved
      solvent. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615698
TI  - Studies of on-line viable yeast biomass with a capacitance biomass monitor.
AB  - A commercially available biomass monitor has been employed in a number of
      applications. For capacitance monitors, a relationship between capacitance
      measurement and cell counts or colony forming units has been reported in the
      literature. However, for use as an online instrument, a more practical
      correlation with the biomass concentration is needed. In this study, we followed
      the batch growth of brewer's yeast and a correlation with viable biomass
      concentration (g DW/L) was demonstrated. This correlation was utilized with the
      capacitance biomass monitor in a control loop to maintain setpoint biomass levels
      in a cyclic reactor under perturbations. Not only did the system demonstrate the
      capability of the biomass monitor to control biomass in such a system, but it
      also confirmed the correlation reported in our earlier work. (c) 1994 John Wiley
      & Sons, Inc.

PMID- 18615699
TI  - High pressure EPR studies of protein mobility in reversed micelles.
AB  - We have investigated the effect of pressure on structural properties of
      subtilisin solubilized in reversed micelles of Tween-85/isopropanol in hexane.
      Electron paramagnetic resonance (EPR) spectra of spin-labeled enzyme indicate a
      reduction in spin-label mobility when the enzyme is transferred from aqueous
      solution to the microemulsion. One explanation for the spectral broadening is a
      change in the protein's active-site conformation and/or dynamics. However, over a
      W(0) range of 80 to 180, EPR spectroscopy could detect no change in the enzyme's
      environment, conformation, or molecular dynamics. The EPR spectra also contained
      a contribution from free spin label located in an environment with a polarity
      roughly between that of propanol and bulk water. No changes in the polarity
      surrounding the free spin label nor in the enzyme's structural properties were
      evident at pressures up to 10,000 psi. Previous work has demonstrated that
      pressure can be used to manipulate the size of some reversed micelles, and the
      EPR data indicated that for this system such pressure tuning of micellar
      properties will not adversely affect the structure of solubilized enzyme. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18615700
TI  - Nasal fossa of mouse and dwarf lemurs (primates, cheirogaleidae).
AB  - Dimensions of the external midface in mammals are sometimes related to olfactory
      abilities (e.g., "olfactory snouts" of strepsirrhine primates). This association
      hinges on the largely unexplored relationship between the protruding midface and
      internal topography of the nasal fossae. Herein, serially sectioned heads of
      embryonic to adult cheirogaleid primates (mouse and dwarf lemurs) and a
      comparative sample were studied. To assess the anteroposterior distribution of
      olfactory epithelium (OE) within the nasal fossa, the surface area of OE and non
      OE was measured in two mouse lemurs (one adult, one infant). Prenatally,
      ethmoturbinal projections appear in an anteroposterior sequence. Fetal mouse
      lemurs, tenrecs, voles, and flying lemurs have four ethmoturbinals that project
      toward the nasal septum. Major distinctions among these mammals include the
      number of turbinals in recesses and the extent of the olfactory recess. Surface
      area measurements in the adult mouse lemur reveal that 31% of the entire nasal
      fossa is lined with OE. The majority is sequestered in a posterior recess (70%
      OE). Anterior to this space, only 28% of the nasal fossa is lined with OE.
      Ethmoturbinal I is lined with relatively less OE (35%) compared with more
      posterior ethmoturbinals (46-57%). Age comparisons support the idea that OE
      increases less than non-OE between ages. Regionally, results suggest that most
      growth in surface area occurs in turbinals. But in all ethmoturbinals, surface
      area of non-OE differs between ages more than that of OE. This study shows that
      the anterior part of the nasal fossa is mostly nonolfactory in Microcebus
      murinus.

PMID- 18615701
TI  - Regulation of polarity in cells devoid of actin bundle system after treatment
      with inhibitors of myosin II activity.
AB  - Interplay of two cytoskeletal systems--microfilaments and microtubules is
      essential for directional cell movement. To better understand the role of those
      cytoskeletal systems in polarization of cells, rat fibroblasts were incubated
      with drugs inhibiting activity of myosin II: blebbistatin and Y-27632. Both drugs
      led to disappearance of actin-myosin bundles and mature focal cell-matrix
      adhesions but did not affect polarization and directional motility. The rate of
      motility even increased after inhibitor treatment. The characteristic feature of
      inhibitor-treated fibroblasts was collapse of the cytoplasm accompanied by
      bundling of microtubules that led to transformation of lamellae into long
      immobile tails. The only exception was the leading anterior lamella which was not
      transformed into the tail and supported directional movement of the cell. The
      tail at the cell rear determined the position of anterior lamella and direction
      of locomotion. Depolymerization of microtubules by colcemid stopped directional
      locomotion of inhibitor-treated cells. These data show that integrity of the
      microtubular system provides the basic mechanism of polarization and orientation
      which is only modified by interactions with actin-myosin system and cell
      substrate adhesions. We suggest that the position of bundled tail microtubules
      and dispersed microtubules in leading lamella determine polarization in cells
      lacking stress fibers and focal adhesions. Thus, polarization is based on
      microtubule-dependent mechanisms both in non-contractile and contractile cells.
      These mechanisms could switch dependent on circumstances as fibroblasts may
      acquire non-contractile phenotype, not only after direct inhibition of myosin II
      but also in certain conditions of microenvironment.

PMID- 18615702
TI  - Memantine leads to behavioral improvement and amyloid reduction in Alzheimer's
      disease-model transgenic mice shown as by micromagnetic resonance imaging.
AB  - Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to
      improve learning and memory in several preclinical models of Alzheimer's disease
      (AD). Memantine has also been shown to reduce the levels of amyloid beta (A beta)
      peptides in human neuroblastoma cells as well as to inhibit A beta oligomer
      induced synaptic loss. In this study, we assessed whether NMDA receptor
      inhibition by memantine in transgenic mice expressing human amyloid-beta
      precursor protein (APP) and presenilin 1 (PS1) is associated with cognitive
      benefit and amyloid burden reduction by using object recognition, micromagnetic
      resonance imaging (micro MRI), and histology. APP/PS1 Tg mice were treated either
      with memantine or with vehicle for a period of 4 months starting at 3 months of
      age. After treatment, the mice were subjected to an object recognition test and
      analyzed by ex vivo micro MRI, and histological examination of amyloid burden.
      micro MRI was performed following injection with gadolinium-DTPA-A beta(1-40). We
      found that memantine-treated Tg mice performed the same as wild-type control
      mice, whereas the performance of vehicle-treated Tg mice was significantly
      impaired (P = 0.0081, one-way ANOVA). Compared with vehicle-treated animals,
      memantine-treated Tg mice had a reduced plaque burden, as determined both
      histologically and by micro MRI. This reduction in amyloid burden correlates with
      an improvement in cognitive performance. Thus, our findings provide further
      evidence of the potential role of NMDA receptor antagonists in ameliorating AD
      related pathology. In addition, our study shows, for the first time, the utility
      of micro MRI in conjunction with gadolinium-labeled A beta labeling agents to
      monitor the therapeutic response to amyloid-reducing agents.

PMID- 18615703
TI  - Tumor immune surveillance defect of X-linked severe combined immunodeficiency is
      not Epstein-Barr virus specific.
AB  - Immunodeficient patients are at an increased risk of developing Epstein-Barr
      virus (EBV) associated lymphomas. We report a patient with X-linked severe
      combined immunodeficiency (X-SCID), who presented with an EBV-negative, B-cell
      non-Hodgkin lymphoma. The tumor did not resolve with chemotherapy or rituximab,
      but only after recovery of functional donor T-cells cell following hematopoietic
      stem cell transplantation (HSCT). This case illustrates that the cancer
      predilection associated with immunodeficient hosts may not be a specific immune
      defect in the recognition of viral specific antigens, and it could be a defect in
      immune surveillance necessary for elimination of cells with abnormalities in
      proliferation, function and/or apoptosis.

PMID- 18615704
TI  - Sensitive periods for developmental toxicity of orally administered artesunate in
      the rat.
AB  - BACKGROUND: Artesunate has been reported to cause embryolethality and
      malformations when administered orally to rats during organogenesis. The purpose
      of this study was to determine the most sensitive period(s) for the induction of
      these effects in order to provide clues about possible mechanisms and to identify
      a short treatment regimen for further studies. METHODS: Pregnant rats were orally
      administered artesunate (10, 17 or 30 mg/kg/day) on single or multiple days of
      gestation. Cesarean sections and fetal evaluations were conducted on Day 21
      postcoitum (pc). RESULTS: Embryolethality, cardiovascular malformations and a
      syndrome of skeletal defects were observed after single doses on days 10 to 14
      pc, while no developmental effects were observed before (day 9 pc) or after (days
      16 or 17 pc) that period. The most sensitive day for embryo lethality was day 11
      pc, where lethality occurred with a very steep dose response (postimplantation
      loss was approximately 15% at 10 mg/kg and 100% at 17 mg/kg/day). The most
      sensitive day for the induction of malformations was day 10 pc. Malformations
      tended to occur in partially resorbed litters and included cardiovascular defects
      and bent and misshapen long bones and scapulae. CONCLUSIONS: The sensitive window
      for developmental toxicity of artesunate in the rat was identified as days 10 to
      14 pc. Single oral doses produced embryolethality and similar cardiovascular and
      skeletal malformations as previously reported in longer term dosing experiments.
      These single dose treatment regimens could be useful to further investigate the
      mechanistic basis for artesunate-induced developmental toxicity.

PMID- 18615705
TI  - Mechanisms of organophosphate resistance in a field population of oriental
      migratory locust, Locusta migratoria manilensis (Meyen).
AB  - The susceptibilities to three organophosphate (OP) insecticides (malathion,
      chlorpyrifos, and phoxim), responses to three metabolic synergists [triphenyl
      phosphate (TPP), piperonyl butoxide (PBO), and diethyl maleate (DEM)], activities
      of major detoxification enzymes [general esterases (ESTs), glutathione S
      transferases (GSTs), and cytochrome P450 monooxygenases (P450s)], and sensitivity
      of the target enzyme acetylcholinesterase (AChE) were compared between a
      laboratory-susceptible strain (LS) and a field-resistant population (FR) of the
      oriental migratory locust, Locusta migratoria manilensis (Meyen). The FR was
      significantly resistant to malathion (57.5-fold), but marginally resistant to
      chlorpyrifos (5.4) and phoxim (2.9). The malathion resistance of the FR was
      significantly diminished by TPP (synergism ratio: 16.2) and DEM (3.3), but was
      unchanged by PBO. In contrast, none of these synergists significantly affected
      the toxicity of malathion in the LS. Biochemical studies indicated that EST and
      GST activities in the FR were 2.1- to 3.2-fold and 1.2- to 2.0-fold,
      respectively, higher than those in the LS, but there was no significant
      difference in P450 activity between the LS and FR. Furthermore, AChE from the FR
      showed 4.0-fold higher activity but was 3.2-, 2.2-, and 1.1-fold less sensitive
      to inhibition by malaoxon, chlorpyrifos-oxon, and phoxim, respectively, than that
      from the LS. All these results clearly indicated that the observed malathion
      resistance in the FR was conferred by multiple mechanisms, including increased
      detoxification by ESTs and GSTs, and increased activity and reduced sensitivity
      of AChE to OP inhibition.

PMID- 18615706
TI  - Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of
      brain ischemia/reperfusion in rats.
AB  - Although dapsone (4,4'-diaminodiphenylsulfone) has been described as a
      neuroprotective agent in occlusive focal ischemia in rats, its mechanism of
      action is still unknown. To explore this mechanism, oxidative, inflammatory and
      apoptotic processes were evaluated in the striatum of adult rats using a model of
      ischemia-reperfusion (I/R), either with or without dapsone treatment. Male Wistar
      rats were submitted to transient middle cerebral artery occlusion for 2 hr,
      followed by reperfusion. Rats were dosed either with dapsone (12.5 mg/kg i.p.) or
      vehicle 30 min before or 30 min after the ischemia onset. Lipid peroxidation (LP)
      and nitrotyrosine contents were measured 22 hr after reperfusion, and
      myeloperoxidase activity was evaluated 46 hr after I/R. Different markers for
      apoptosis and necrosis were also evaluated both at 24 and 72 hr after I/R
      experimental procedure. LP increased by 37% in ischemic animals vs controls, and
      this effect was reversed by dapsone treatments. A similar effect was observed
      regarding nitrotyrosine striatal contents. Myeloperoxidase activity, a marker of
      inflammatory response, increased 3.7-fold in ischemic animals vs. control rats,
      and dapsone treatment antagonized that effect. Although apoptosis was increased
      by the effect of ischemia at both evaluation times, dapsone antagonized that
      effect only at 72 hr after surgery. Dapsone antagonized all of the I/R end points
      measured, showing a remarkable ability to decrease markers of damage through
      antioxidant, antiinflammatory, and anti-apoptotic effects.

PMID- 18615707
TI  - Up-regulation of lysozyme gene expression during metamorphosis and immune
      challenge of the cotton bollworm, Helicoverpa armigera.
AB  - Lysozymes act as crucial bacteriolytic enzymes in insect immune system by
      hydrolyzing the beta (1-->4) bonds between N-acetylglucosamine and N
      acetylmuramic acid in the peptidoglycan of prokaryotic cell walls. We have
      isolated and characterized a Helicoverpa armigera cDNA encoding an insect
      lysozyme named HaLyz. We amplified a fragment by PCR, using degenerate primers
      derived from the conservative amino acid sequences for performing 5' and 3' RACE.
      The full-length cDNA was 661 base pairs. The theoretical pI and molecular weight
      of the protein were computed to be 9.08 and 15.6 kDa, respectively. Prokaryotic
      expression of the HaLyz ORF by Escherichia coli confirmed the calculated
      molecular weight of the protein. The deduced 135 amino acids showed high homology
      with known lysozymes from other insects, ranging from 47% to 89% by BLASTp search
      in NCBI. Analyses revealed that this protein has a typical lysozyme C signature
      among amino acids 93-111, CNVTCAEMLLDDITKASTC. An interesting relation between
      immunity and larva to pupa metamorphosis in insects was discovered. Real time-PCR
      showed that HaLyz gene expression was transiently enhanced at the onset of
      metamorphosis of the cotton bollworm, Helicoverpa armigera. The gene expression
      was up-regulated after the injection of E. coli or entomopathogenic fungi,
      Beauveria bassiana, but showed different expression patterns.

PMID- 18615709
TI  - Psychological services for returning veterans and their families: evolving
      conceptualizations of the sequelae of war-zone experiences.
AB  - The provision of effective and timely behavioral health care for veterans
      returning from the conflicts in Iraq and Afghanistan has become the focus of
      national attention. In this special issue, attempts to provide psychological care
      for service members and their families are examined in light of three key
      constructs. First, it is contended that at no other time in history has more
      attention been paid to the psychological consequences of engaging in combat.
      Second, for the first time in recorded warfare, psychological morbidity is likely
      to far outstrip physical injury associated with combat. Finally, although
      posttraumatic stress disorder and traumatic brain injury are serious concerns,
      most service members return without significant physical or psychological injury
      and will be able to return to functioning without notable problems. Accurate
      diagnosis, a focus on resilience, and the expectation of readjustment are
      essential precepts that should guide clinical efforts and resource allocation.

PMID- 18615708
TI  - CD8+ cutaneous T-cell lymphoma successfully treated with bexarotene: a case
      report and review of the literature.
AB  - CD8+ cutaneous T-cell lymphoma (CTCL) is a relatively rare subset of the non
      Hodgkins lymphomas. Bexarotene has been FDA-approved for the treatment of CTCL,
      but previous studies have been conducted on CD4+ CTL and there have been no
      reports about its use in CD8+ CTCL. Herein, we report on a patient whose CD8+
      CTCL completely responded to treatment with bexarotene.

PMID- 18615710
TI  - Generation and characterization of a Gdf1 conditional null allele.
AB  - Growth differentiation factor-1 (GDF1), a TGF-beta superfamily member,
      participates in early embryo patterning. Later functions are implied by the Gdf1
      expression in the peripheral and central nervous system. Such roles of the gene
      have been difficult to study, because Gdf1 null mice die during late
      embryogenesis. Here, we report the production of a mouse carrying a conditional
      Gdf1 allele, with exon 2 flanked by loxP sites. Crossing these mice with
      CaMKIIalpha-Cre mice resulted in Gdf1 ablation in the forebrain postnatally. Such
      mice displayed no behavioral changes or altered expression levels in a set of
      hippocampal genes examined. However, excision of the floxed Gdf1 exon caused
      increased expression of the remaining part of the bicistronic Uog1-Gdf1
      transcript in the hippocampus. This indicates that the transcript level is
      regulated by a negative feedback-loop, sensing presence of either the protein or
      the mRNA region encoded by Gdf1 exon 2.

PMID- 18615711
TI  - Potential for efficacy of the oncolytic Herpes simplex virus 1716 in patients
      with oral squamous cell carcinoma.
AB  - BACKGROUND: : Herpes simplex virus (HSV) 1716 is a selectively replicating
      oncolytic virus. Our objective was to assess the potential efficacy of HSV1716 in
      patients with oral squamous cell carcinoma (SCC) by intratumoral injection.
      METHODS: : Twenty patients with oral SCC had a single intratumoral injection of
      HSV1716 at a dose of 105 pfu (plaque forming unit) or 5 x 105 pfu. Injections
      were done at 1, 3, or 14 days before surgical resection. The tumors were assessed
      for evidence of viral replication and necrosis. Immunologic response to virus and
      toxicity was also assessed. RESULTS: : Intratumoral injections were well
      tolerated with no adverse effects. Evidence of biological activity was lacking,
      with no increase in detectable virus in tumor samples. CONCLUSION: : Intratumoral
      injection of HSV1716 is safe but with little evidence for viral replication or
      efficacy. Further studies at higher doses are required to determine the potential
      efficacy of this virus in head and neck cancer.

PMID- 18615712
TI  - Analysis of electrostatic contributions to the selectivity of interactions
      between RING-finger domains and ubiquitin-conjugating enzymes.
AB  - The zinc-coordinated protein motifs known as RING-finger domains, present on a
      class of ubiquitin ligases (E3's), recruit ubiquitin-conjugating enzymes (E2s),
      tethering them to substrate proteins for covalent modification with ubiquitin.
      Each RING-finger domain can recruit different E2s, and these interactions are
      frequently selective, in that certain RING-finger domains associate
      preferentially with certain E2s. This selectivity acquires particular biological
      relevance when the recruited E2s exert specialized functions. We have explored
      the determinants that specify the presence or absence of experimentally
      detectable interaction between two RING-finger domains, those on RNF11 and
      RNF103, and two E2s, UBC13, a specialized E2 that catalyzes ubiquitin chain
      elongation through Lys63 of ubiquitin, and UbcH7, which mediates
      polyubiquitylation through Lys48. Through the iterative use of computational
      predictive tools and experimental validations, we have found that these
      interactions and their selectivity are partly governed by the combinations of
      electrostatic interactions linking specific residues of the contact interfaces.
      Our analysis also predicts that the main determinants of selectivity of these
      interactions reside on the RING-finger domains, rather than on the E2s. The
      application of some of these rules of interaction selectivity has permitted us to
      experimentally manipulate the selectivity of interaction of the RING-finger
      domain-E2 pairs under study.

PMID- 18615713
TI  - A novel binding pocket of cyclin-dependent kinase 2.
AB  - The cyclin-dependent kinase 2 (cdk2) is a serine/threonine protein kinase that
      plays a key role in the cell cycle control system of all eukaryotic organisms. It
      has been a much studied drug target for potential anticancer therapy. Most cdk2
      inhibitors in clinical development target almost exclusively the catalytic ATP
      binding pocket of cdk2. However, several five amino-acid peptide inhibitors that
      are directed towards a noncatalytic binding pocket of cdk2 are reported here.
      Upon binding to this new pocket located at the cdk2 and cyclin interface, these
      peptide inhibitors are found to disrupt the cdk2/cyclin E complex partially and
      diminish its kinase activity in vitro.

PMID- 18615714
TI  - Human FEZ1 has characteristics of a natively unfolded protein and dimerizes in
      solution.
AB  - The fasciculation and elongation protein Zeta 1 (FEZ1) is the mammalian
      orthologue of the Caenorhabditis elegans protein UNC-76, which is necessary for
      axon growth. Human FEZ1 interacts with Protein Kinase C (PKC) and several
      regulatory proteins involved in functions ranging from microtubule associated
      transport to transcriptional regulation. Theoretical prediction, circular
      dichroism, fluorescence spectroscopy, and limited proteolysis of recombinant FEZ1
      suggest that it contains disordered regions, especially in its N-terminal region,
      and that it may belong to the group of natively unfolded proteins. Small angle X
      ray scattering experiments indicated a mainly disordered conformation, proved
      that FEZ1 is a dimer of elongated shape and provided overall dimensional
      parameters for the protein. In vitro pull down experiments confirmed these
      results and demonstrated that dimerization involves the N-terminus. Ab-initio 3D
      low resolution models of the full-length conformation of the dimeric constructs
      6xHis-FEZ1(1-392) and 6xHis-FEZ1(1-227) were obtained. Furthermore, we performed
      in vitro phosphorylation assays of FEZ1 with PKC. The phosphorylation occurred
      mainly in its C-terminal region, and does not cause any significant
      conformational changes, but nonetheless inhibited its interaction with the FEZ1
      interacting domain of the protein CLASP2 in vitro. The C terminus of FEZ1 has
      been reported to bind to several interacting proteins. This suggests that FEZ1
      binding and transport function of interacting proteins may be subject to
      regulation by phosphorylation.

PMID- 18615715
TI  - Solution structure of the GUCT domain from human RNA helicase II/Gu beta reveals
      the RRM fold, but implausible RNA interactions.
AB  - Human RNA helicase II/Gu alpha (RH-II/Gu alpha) and RNA helicase II/Gu beta (RH
      II/Gu beta) are paralogues that share the same domain structure, consisting of
      the DEAD box helicase domain (DEAD), the helicase conserved C-terminal domain
      (helicase_C), and the GUCT domain. The N-terminal regions of the RH-II/Gu
      proteins, including the DEAD domain and the helicase_C domain, unwind double
      stranded RNAs. The C-terminal tail of RH-II/Gu alpha, which follows the GUCT
      domain, folds a single RNA strand, while that of RH-II/Gu beta does not, and the
      GUCT domain is not essential for either the RNA helicase or foldase activity.
      Thus, little is known about the GUCT domain. In this study, we have determined
      the solution structure of the RH-II/Gu beta GUCT domain. Structural calculations
      using NOE-based distance restraints and residual dipolar coupling-based angular
      restraints yielded a well-defined structure with beta-alpha-alpha-beta-beta-alpha
      beta topology in the region for K585-A659, while the Pfam HMM algorithm defined
      the GUCT domain as G571-E666. This structure-based domain boundary revealed false
      positives in the sequence homologue search using the HMM definition. A structural
      homology search revealed that the GUCT domain has the RRM fold, which is
      typically found in RNA-interacting proteins. However, it lacks the surface
      exposed aromatic residues and basic residues on the beta-sheet that are important
      for the RNA recognition in the canonical RRM domains. In addition, the overall
      surface of the GUCT domain is fairly acidic, and thus the GUCT domain is unlikely
      to interact with RNA molecules. Instead, it may interact with proteins via its
      hydrophobic surface around the surface-exposed tryptophan.

PMID- 18615717
TI  - Purification of a recombinant protein produced in a baculovirus expression system
      by immobilized metal affinity chromatography.
AB  - Over the past 10 years, the baculovirus-insect cell system has become a powerful
      and versatile tool for the expression of a variety of heterologous proteins. In
      order to simplify separation of a cloned protein from the baculovirus-insect
      expression system, we have cloned a gene encoding for the protein of interest, a
      structural protein (VP2) of a strain (E/DEL) of infectious bursal disease virus
      (IBDV), with a metal ion binding site (His)(5) at its C-terminus. This chimeric
      protein (VP2H) has been expressed and one-step affinity purified with immobilized
      metal ions (Ni(+2)). With antigen capture-enzyme-linked immunosorbent assay (AC
      ELISA), we determined that the conformation of this chimeric protein was no
      different from the recombinant wild-type VP2 protein. However, the two proteins
      (VP2 and VP2H) can be distinguished and resolved by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and detected immunologically
      following Western blotting. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615718
TI  - A mathematical model for the bacterial oxidation of a sulfide ore concentrate.
AB  - The effect of dilution rate and feed solids concentration on the bacterial
      leaching of a pyrite/arsenopyrite ore concentrate was studied. A mathematical
      model was developed for the process based on the steady-state data collected over
      the range of dilution rates (20 to 110 h) and feed solids concentrations (6 to
      18% w/v) studied. A modified Monod model with inhibition by arsenic was used to
      model bacterial ferrous ion oxidation rates. The model assumes that (i) pyrite
      and arsenopyrite leaching occurs solely by the action of ferric iron produced
      from the bacterial oxidation of ferrous iron and (ii) bacterial growth rates are
      proportional to ferrous ion oxidation rate. The equilibrium among the various
      ionic species present in the leach solution that are likely to have a significant
      effect on the bioleach process were included in the model. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18615719
TI  - Partition coefficients of substrates and products and solvent selection for
      biocatalysis under nearly anhydrous conditions.
AB  - The effect of solvent on the activity of mushroom tyrosinase toward three
      substrates was studied at a constant water activity of either 0.74 or 0.86. No
      simple correlation was observed between enzyme activity and log P, but partition
      coefficients of substrate (P(s)) and product (P(p)) gave systematic relations
      with enzyme activity. When initial reaction rates were considered, there was a
      bellshaped relationship between enzyme activity and P(s) with an optimal P(s) for
      each substrate. This can be explained by assuming that the solvent affected the
      enzyme activity primarily by affecting the substrate concentration in the aqueous
      layer around the catalyst where the enzymic reaction occurs. When long-term
      reaction rates were considered, a high P(p)/P(s) ratio was consistent with
      preservation of enzyme activity. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615720
TI  - Feeding heterogeneity in ciliate populations: Effects of culture age and
      nutritional state.
AB  - We have used a novel approach in conjunction with flow cytometry to quantify the
      biological heterogeneity of populations of the ciliate Tetrahymena pyriformis. It
      was found that the rate of particle uptake of exponentially growing cells is not
      uniform among cells and partially correlated with cell size. The physiological
      state and growth history of the culture was found to affect to a large degree the
      population's feeding heterogeneity. Stationary phase populations exhibited more
      uniform feeding behavior, as cell aging affects all cells and effectively reduces
      their ability to feed. Cells that were removed from the growth medium and
      resuspended in nonnutritive medium exhibited a more heterogeneous feeding
      behavior. The starved cells were stimulated to feed at considerably higher rates,
      and the stimulatory effect was more pronounced for larger cells. It is therefore
      demonstrated that population heterogeneity has to be evaluated in conjunction
      with the populations growth state as it is determined by the history of the
      population's growth and nutritional state. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615721
TI  - Cellulose morphology and enzymatic reactivity: A modified solute exclusion
      technique.
AB  - An expeditious and accurate simplification of Stone and Scallan's solute
      exclusion technique was developed, thereby avoiding several sources of
      experimental error coupled with the determination of cellulose pore volume. Using
      this method, it is shown that cellulolytic enzymes do not enter into the
      micropores of five studied celluloses. These results suggestes that hydrolysis
      occurs initially at the external surface of the fibers. This surface area was
      calculated with the help of adsorption isotherms of bovine serum albumin. The
      obtained values for the different samples agree with the microscopically observed
      cellulose morphology. The correlation obtained by several authors relating
      cellulose porosity and its digestibility is explained as a consequence of the
      lower crystallinity and easier fragmentation of the more porous celluloses during
      hydrolysis. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615722
TI  - Ribosomal protein limitations in Escherichia coli under conditions of high
      translational activity.
AB  - Details of the mechanism for ribosome synthesis have been incorporated in the
      single-cell Escherichia coli model, which enable us to predict the amount of
      protein synthesizing machinery under different environmental conditions. The
      predictions agree quite well with available experimental data. The model predicts
      that ribosomal protein limitations are important when the translational apparatus
      is in high demand. Ribosomal RNA synthesis is induced by an increase in
      translational activity, which, in turn, stimulates ribosomal protein synthesis.
      However, as the demand increases still more, the ribosomal protein mRNA must
      compete with the plasmid mRNA for ribosomes, and the efficiency of translation of
      ribosomal proteins is reduced. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615723
TI  - Structured model of genetic control via the lac promoter in Escherichia coli.
AB  - A model that describes induction of protein synthesis from lac-based promoters
      has been developed and incorporated into the single-cell model of Escherichia
      coli with transcriptional and translational modifications. Unlike previous models
      of lac-based promoters, this model allows a priori prediction of the
      intracellular parameters controlling transcription from lac-based promoters with
      only the extracellular levels of substrate and inducer as inputs. Because of the
      structural detail of the model, it is possible to simulate different genetic
      constructions for comparison, such as Lacl(q) strains versus wild-type cells, or
      including lacl on a multicopy plasmid. Expression from lac to tac promoters is
      predicted to yield 5% and 30% of the total cellular protein, respectively, with a
      pBR322-type plasmid. The model predicts the experimental observation that the
      Lacl(q) strain is not as fully induced as the wild-type strains, even at higher
      inducer concentrations. Additionally, the model predicts the right order of
      magnitude of protein production from lac and tac promoters when mechanisms for
      attenuation of transcription at lower translational efficiency are considered.
      Finally, the model predicts that for high copy number systems ribosomes become
      limiting in the synthesis of plasmid-encoded proteins. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18615724
TI  - Kinetic analysis of enzymatic chiral resolution by progress curve evaluation.
AB  - The present study deals with kinetic modeling of enzyme-catalyzed reactions by
      integral progress curve analysis, and shows how to apply this technique to
      kinetic resolution of enantiomers. It is shown that kinetic parameters for both
      enantiomers and the enantioselectivity of the enzyme may be obtained from the
      progress curve measurement of a racemate only.A parameter estimation procedure
      has been established and it is shown that the covariance matrix of the obtained
      parameters is a useful statistical tool in the selection and verification of the
      model structure. Standard deviations calculated from this matrix have shown that
      progress curve analysis yields parameter values with high accuracies.Potential
      sources of systematic errors in (multiple) progress curve analysis are addressed
      in this article. Amongst these, the following needed to be dealt with: (1) the
      true initial substrate concentrations were obtained from the final amount of
      product experimentally measured (mass balancing); (2) systematic errors in the
      initial enzyme concentration were corrected by incorporating this variable in the
      fitting procedure as an extra parameter per curve; and (3) enzyme inactivation is
      included in the model and a first-order inactivation constant is
      determined.Experimental verification was carried out by continuous monitoring of
      the hydrolysis of ethyl 2-chloropropionate by carboxylesterase NP and the alpha
      chymotrypsin-catalyzed hydrolysis of benzoylalanine mathyl ester in a pH-stat
      system. Kinetic parameter values were obtained with high accuracies and model
      predictions were in good agreement with independent measurements of enantiomeric
      excess values or literature data. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615725
TI  - Glycosidase activities of the 293 and NS0 cell lines, and of an antibody
      producing hybridoma cell line.
AB  - We have previously demonstrated that Chinese hamster ovary (CHO) cell lysates
      harbor sialidase, beta-galactosidase, beta-hexosaminidase, and fucosidase
      activities that can accumulate extracellularly in CHO cell culture, thereby
      potentially leading to extracellular modification of glycoprotein
      oligosaccharides. The sialidase activity in CHO cell lysates was surprisingly
      active and stable at pH 7.5, with a half-life of 57 h at 37 degrees C.We have
      extended this work to determine whether 293, NS0, or hybridoma cell lysates
      contain similar glycosidase activities. The pH-activity profiles of beta
      galactosidase and beta-hexosaminidase in lysates of these three cell lines
      resemble the pH-activity profiles for these enzymes in CHO cell lysate, whereas
      the pH-activity profiles of sialidase and fucosidase appear to be cell-type
      dependent. Sialidase activities were relatively stable at pH 4.5 in 293, NS0, and
      hybridoma cell lysates. However, the activities in 293 and NS0 cell lysates were
      unstable at pH 7.5, with no activity remaining after a 2-h incubation at 37
      degrees C. The sialidase activity in hybridoma cell lysate was moderately stable
      at pH 7.5 with 30% of the activity remaining after a 2-h incubation at 37 degrees
      C. We conclude that the sialidase activites from 293, NS0, and hybridoma cells
      have characteristics similar to the vast majority of reported mammalian sialidase
      activities, and that these activities are markedly differant from the CHO cell
      sialidase activity.Finally, sialidase, beta-galactosidase, beta-hexosaminidase,
      and fucosidase activities were measured at pH 7 in cell-free bioreactor
      supernatants of the hybridoma cell line. As previously observed in CHO cell
      culture, all four glycosidase activities were present in the hybridoma
      supernatants. However, the sialidase activity in hybridoma supernatant was an
      order of magnitude lower than in CHO cell culture supernatant despite the fact
      that the hybridoma cell lysis rate was an order of magnitude higher. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18615726
TI  - Electrochemical disinfection of bacteria in drinking water using activated carbon
      fibers.
AB  - A novel electrochemical reactor employing activated carbon fiber (ACF) electrodes
      was constructed for disinfecting bacteria in drinking water. Escherichia coli
      adsorbed preferentially onto ACF rather than to carbon-cloth or granular
      activated carbon. E. coli cells, which adsorbed onto the ACF, were killed
      electrochemically when a potential of 0.8 V vs. a saturated calomel electrode
      (SCE) was applied. Drinking water was passed through the reactor in stop-flow
      mode: 2mL/min for 12 h, o L/min for 24 h, and 1 mL/min for 6 h. At an applied
      potential of 0.8 V vs, SCE, viable cell concentration reamined below 30 cells/mL.
      In the absence of an applied potential, bacteria grew to a maximum concentration
      of 9.5 x 10(3) cells/mL. After continuous operation at 0.8 V vs. SCE, cells
      adsorbed onto the ACF could not be observed by scanning electron microscopy. In
      addition, chlorine in drinking water was completely removed by the reactor.
      Therefore, clean and efficient inactivation of bacteria in drinking water was
      successfully performed. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615727
TI  - Ammonia inhibition of hybridomas propagated in batch, fed-batch, and continuous
      culture.
AB  - The nature and temporal development of ammonia inhbition were investigated in
      batch, fed-batch, and continuous cultures. Significant inhibition was observed
      when cells were inoculated in serum-containing or chemically defined medium
      containing more than 2 mM of ammonia. In contrast, no inhibition was observed at
      greater than 10 mM when the ammonia concentration was gradually increased over
      the span of a batch culture by feeding ammonium chloride. Strong growth
      inhibition was observed after each of five step changes (2.8 --> 3.7 --> 4.0 -->
      4.9 --> 7.7 --> 13.5 mM) in continuous culture. Following a period of adaptation
      at each higher value, the viable cell density stabilized at a new lower value.
      The lowering in viable cell density was caused by an increase in specific death
      rate and a decreased cell yield on glucose, glutamine, and oxygen. Increased
      ammonia concentration had little or no effect on the steady-state specific growth
      kinetics or specific antibody productivity. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615728
TI  - Conditional activation of a single-copy L1 transgene in mice by Cre.
AB  - The synthetic L1 retrotransposon, ORFeus, is useful for probing mechanisms of L1
      retrotransposition in vivo and for genome-wide mouse mutagenesis because of its
      high level of activity. To achieve controlled activation of ORFeus in mice, we
      constructed ORFeus(LSL), in which ORFeus coding sequences were separated from the
      promoter by a loxP-beta-geo-stop-loxP (LSL) cassette, and derived transgenic
      mouse lines containing single-copy ORFeus(LSL). We observed tissue-specific
      ORFeus activation by crossing ORFeus(LSL) to various Cre-expressing lines,
      specifically in the germ line or the pancreas, providing definite evidence that
      all host factors and machinery required posttranscriptionally for L1
      retrotransposition are available in somatic tissues in living animals. Notably,
      the single-copy ORFeus transgene is about threefold more active per copy than a
      previously described multicopy ORFeus transgene in the germ line and even more
      active somatically. This conditional transgenic ORFeus mouse model should allow
      further exploration of posttranscriptional cellular requirements for L1
      retrotransposition and facilitate the development of ORFeus mouse lines suitable
      for in vivo mutagenesis.

PMID- 18615729
TI  - Real time monitoring of BMP Smads transcriptional activity during mouse
      development.
AB  - SUMMARY: Bone morphogenetic protein (BMP) signaling is a key pathway in the
      patterning and development of organisms as diverse as fruit fly and humans.
      However, the determination of net BMP signaling, paramount to understanding
      organogenesis, is limited to the analysis of fixed material. We generated a
      transgenic mouse that reports the transcriptional response of BMP Smad activation
      by coupling a well established BMP response element (BRE), isolated from the Id1
      promoter, to green fluorescent protein (BRE:gfp). We monitored BMP Smad
      transcriptional activity in fresh and fixed BRE:gfp embryos. GFP expression was
      observed where expected on the basis of known signaling sites, but also in
      specific cell populations in which BMP signaling had been implicated but not
      directly demonstrated. Deletion of Smad5 reduced GFP in vivo as expected. The
      BRE:gfp transgenic mice are a novel tool, which will facilitate the
      identification of specific BMP Smad responsive cell types and allow BMP Smad
      signaling to be monitored in real time, supporting studies in development and
      disease.

PMID- 18615730
TI  - Development of a gene-trap vector with a highly sensitive fluorescent protein
      reporter system for expression profiling.
AB  - SUMMARY: Combining high-content screening (HCS) with random gene-trap mutagenesis
      could be a powerful tool to investigate transcriptional networks, cell signaling,
      chemical genetics, and developmental processes. However, a critical limitation
      has been poor quantification of reporter expression per cell. To overcome this
      hurdle, we generated a variety of Gtx-based expression cassettes and re-evaluated
      translational enhancement of arrayed Gtx segments in tandem by HCS. We then
      modified the cassette into a new polyA trap vector, which consists of a variant
      of yellow fluorescent protein, Venus, in combination with the Gtx segments.
      Expression of Venus was detected in about 60% of trapped genes assayed in
      embryonic stem cell (ESC) cultures, comparable to expression screening of LacZ
      based vectors. Furthermore, tetraploid aggregations using a clone encoding a gene
      trap insertion into Twist2 demonstrated identical spatiotemporal expression
      between Venus and Twist2. This highly sensitive reporter system is amenable to
      high-throughput expression-based real-time HCS including single cell analyses.

PMID- 18615731
TI  - Microsatellite instability and loss of heterozygosity in squamous cell carcinoma
      of the head and neck.
AB  - BACKGROUND: Microsatellite instability (MSI) in head and neck squamous cell
      carcinoma (HNSCC) has been reported with a wide range of frequencies. The aim of
      our study was to disclose the frequency and basis of MSI in HNSCC and to
      correlate MSI and findings on loss of heterozygosity (LOH) with the clinical
      data. METHODS: We analyzed MSI and LOH in 91 tumors. All tumors presenting
      instability were analyzed for the expression of mismatch repair genes (MMR)
      proteins. RESULTS: Low-level microsatellite instability (MSI-L) was seen in 7.7%
      of the HNSCC. None of the MSI-L tumors had aberrant MMR protein expression. LOH
      rates up to 57% were identified for different regions on chromosome 3p. For the
      marker D10S197, we found a significant correlation between LOH and tumor stage
      IV. CONCLUSION: Our results indicate that MMR gene inactivation is rare among
      primary HNSCC. In contrast, the MSI-L phenotype plays a role in a small subset of
      tumors. LOH on chromosome arm 3p and 10p12 seems to be involved in tumorigenesis
      and progression HNSCC, respectively.

PMID- 18615732
TI  - Definitive radiation therapy for squamous cell carcinoma of the soft palate.
AB  - BACKGROUND: We report the University of Florida experience with soft-palate
      carcinoma treated with radiotherapy alone or combined with adjuvant chemotherapy
      and/or neck dissection for residual disease in the neck. METHODS: A total of 145
      patients treated with curative intent from 1963 to 2004 were included. Potential
      follow-up was > or =2 years. RESULTS: Local control rates at 5 years were: T1,
      90%; T2, 91%; T3, 67%; T4, 57%. Nodal control rates at 5 years were: N0, 90%; N1,
      82%; N2, 68%; N3, 71%. Ultimate local-regional control rates at 5 years were:
      stage I, 89%; stage II, 88%; stage III, 96%; stage IVA, 63%; stage IVB, 43%. In
      multivariate analysis, overall treatment time significantly affected local and
      ultimate local-regional control, and nodal stage significantly affected overall
      survival. Overall survival rate at 5 years was 44%. Cause-specific survival rate
      at 5 years was 73%. CONCLUSIONS: The likelihood of cure after definitive
      radiotherapy is relatively high and is impacted by disease extent and overall
      treatment time.

PMID- 18615733
TI  - Deletion of GAD67 in dopamine receptor-1 expressing cells causes specific motor
      deficits.
AB  - The medium spiny neurons (MSNs), which comprise the direct and indirect output
      pathways from the striatum, use gamma-aminobutyric acid (GABA) as their major
      fact-acting neurotransmitter. We generated mice carrying a conditional allele of
      the Gad1 gene, which encodes GAD67, one of the two enzymes responsible for GABA
      biosynthesis, and bred them to mice expressing Cre recombinase at the dopamine D1
      receptor locus (Drd1a) to selectively reduce GABA synthesis in the direct output
      pathway from the striatum. We show that these mice are deficient in some types of
      motor skills, but normal for others, suggesting a differential role for GABA
      release from D1 receptor-containing neurons.

PMID- 18615734
TI  - A balanced chromosomal translocation disrupting ARHGEF9 is associated with
      epilepsy, anxiety, aggression, and mental retardation.
AB  - Clustering of inhibitory gamma-aminobutyric acid(A) (GABA(A)) and glycine
      receptors at synapses is thought to involve key interactions between the
      receptors, a "scaffolding" protein known as gephyrin and the RhoGEF collybistin.
      We report the identification of a balanced chromosomal translocation in a female
      patient presenting with a disturbed sleep-wake cycle, late-onset epileptic
      seizures, increased anxiety, aggressive behavior, and mental retardation, but not
      hyperekplexia. Fine mapping of the breakpoint indicates disruption of the
      collybistin gene (ARHGEF9) on chromosome Xq11, while the other breakpoint lies in
      a region of 18q11 that lacks any known or predicted genes. We show that defective
      collybistin transcripts are synthesized and exons 7-10 are replaced by cryptic
      exons from chromosomes X and 18. These mRNAs no longer encode the pleckstrin
      homology (PH) domain of collybistin, which we now show binds phosphatidylinositol
      3-phosphate (PI3P/PtdIns-3-P), a phosphoinositide with an emerging role in
      membrane trafficking and signal transduction, rather than phosphatidylinositol
      3,4,5-trisphosphate (PIP3/PtdIns-3,4,5-P) as previously suggested in the
      "membrane activation model" of gephyrin clustering. Consistent with this finding,
      expression of truncated collybistin proteins in cultured neurons interferes with
      synaptic localization of endogenous gephyrin and GABA(A) receptors. These results
      suggest that collybistin has a key role in membrane trafficking of gephyrin and
      selected GABA(A) receptor subtypes involved in epilepsy, anxiety, aggression,
      insomnia, and learning and memory.

PMID- 18615735
TI  - Dock4 regulates dendritic development in hippocampal neurons.
AB  - Dendrite development is required for establishing proper neuronal connectivity.
      Rho-family small GTPases have been reported to play important roles in the
      regulation of dendritic growth and morphology. However, the molecular mechanisms
      that control the activities of Rho GTPases in developing dendrites are not well
      understood. In the present study we found Dock4, an activator of the small GTPase
      Rac, to have a role in regulating dendritic growth and branching in rat
      hippocampal neurons. Dock4 is highly expressed in the developing rat brain,
      predominantly in hippocampal neurons. In dissociated cultured hippocampal
      neurons, the expression of Dock4 protein is up-regulated after between 3 and 8
      days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4
      results in reduced dendritic growth and branching. Conversely, overexpression of
      Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and
      dendritic branches. These morphological effects elicited by Dock4 and ELMO2
      require Rac activation and the C-terminal Crk-binding region of Dock4. Indeed,
      Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings
      demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis
      in hippocampal neurons.

PMID- 18615737
TI  - Antioxidants partially restore glutamate transport defect in leber hereditary
      optic neuropathy cybrids.
AB  - Leber hereditary optic neuropathy (LHON) is a mitochondrial disease characterized
      by visual loss resulting from retinal ganglion cell degeneration. Despite the
      important role of respiratory chain deficiency and oxidative stress induced by
      mtDNA point mutations affecting complex I, excitotoxic injury has been postulated
      as a concurrent pathogenic factor. We used transmitochondrial cybrid cell lines
      constructed using enucleated fibroblasts from three LHON probands carrying the
      most severe 3460/ND1 mutation and three controls as mitochondria donors, and the
      osteosarcoma-derived mtDNA-less cells, to study the possible efficacy of two
      selected antioxidant compounds in preventing glutamate uptake reduction
      previously observed in LHON cybrids. We demonstrated that two antioxidants,
      Trolox and decylubiquinone, partially restore glutamate transport impairment
      occurring in LHON cybrids. Rotenone, a classic complex I inhibitor, did not
      worsen the glutamate uptake defect present in LHON cybrids under basal conditions
      but significantly reduced glutamate transport in control cybrids. Furthermore, we
      observed that LHON cybrids showed an increased protein carbonylation under basal
      conditions, not further affected by rotenone and partially counteracted by
      antioxidants. Our findings strengthen the hypothesis that the complex I defect
      associated with LHON causes free radical overproduction, which is responsible for
      glutamate transport inhibition. We suggest that selected antioxidants may be
      clinically tested in LHON patients and relatives to restore glutamate uptake
      defect caused by LHON-associated free radical overproduction.

PMID- 18615736
TI  - Opposing effects of P2X(7) and P2Y purine/pyrimidine-preferring receptors on
      proliferation of astrocytes induced by fibroblast growth factor-2: implications
      for CNS development, injury, and repair.
AB  - Extracellular nucleotides play important trophic roles in development and central
      nervous system (CNS) injury, but the functions of distinct purinergic receptors
      and related signaling pathways have not been fully elucidated. In the present
      study we identified opposing effects of P2X and P2Y receptors on the ability of
      FGF2 to induce proliferation in primary cultures of rat cortical astrocytes. Low
      concentrations of ATP enhanced DNA synthesis induced by FGF2, whereas high
      concentrations inhibited FGF2-induced proliferation. Comparison of concentration
      response experiments with ATP and 2',3'-O-(4-benzoyl)-benzoyl-ATP (BzATP)
      indicated that the inhibitory effect was mediated by P2X(7) receptors.
      Interestingly, activation of P2X(7) receptors led to a state of reversible growth
      arrest rather than cell death. Selectivity studies showed that proliferation
      evoked by epidermal growth factor and platelet-derived growth factor was also
      inhibited by P2X(7) receptors, but P2X(1) or P2X(3) receptors did not inhibit
      proliferation induced by FGF2. A marker of mitosis, phosphohistone-3, was reduced
      by BzATP and increased by UTP, suggesting that the enhancing effect of ATP on
      FGF2-induced proliferation was mediated by P2 purine/pyrimidine receptors.
      Phosphorylation of the growth arrest-related protein kinases p38/MAPK and
      SAPK/JNK was strongly increased by BzATP but only weakly affected by UTP. We
      conclude that P2Y purine/pyrimidine receptors enhance proliferation induced by
      FGF2 in astrocytes, whereas stimulation of P2X(7) receptors inhibits
      proliferation by shifting cells to a state of reversible growth arrest that may
      be mediated by protein kinase signaling. These trophic actions of P2X(7) and P2Y
      purine/pyrimidine receptors may contribute to the regulation of CNS development,
      adult neurogenesis, and the response of astrocytes to injury.

PMID- 18615739
TI  - Extraction of cephalosporin C from whole broth and separation of desacetyl
      cephalosporin C by aqueous two-phase partition.
AB  - Cephalosporin C was extracted from diluted or whole broth by PEG/salt aqueous two
      phase systems. Parameters such as PEG molecular weight, salt type, pH, and salt
      concentration were investigated for finding a suitable extraction system. In PEG
      600/ammonium sulfate or phosphate systems, K(c) (partition coefficienct of
      cephalosporin C) was observed to be larger than 1, with K(d) (partition
      coefficient of desacetyl cephalosporin C) being smaller than 1. The particular
      values of these coefficients would imply that the difficult separation of
      cephalosporin C and desacetyl cephalosporin C could possibly be achieved via the
      aqueous two-phase extraction. The addition of surfactants, water-miscible
      solvents, and neutral salts for enhancement of the separation efficiency was also
      investigated. The addition of surfactants to the system did not affect the
      separation efficiency substantially. K(c) would increase whereas K(d) decreased
      as a result of the addition of acetone, MeOH, EtOH, IPA, and n-BuOH. Meanwhile
      both K(c) and K(d) would decrease whenever neutral salts, NaCl, KCl, Kl, or KSCN,
      were added. The partitioning behavior of cephalosporin C and desacetyl
      cephalosporin C in filtered, whole, and different batches of broth was notably
      quite similar to that of diluted broth. The recovery yield of cephalosporin C in
      whole broth extraction was observed to be a function of centrifugal force used in
      phase separation. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615740
TI  - Interactions between animal cells and gas bubbles: The influence of serum and
      pluronic F68 on the physical properties of the bubble surface.
AB  - We describe a method by which the degree of bubble saturation can be determined
      by measuring the velocity of single bubbles at different heights from the bubble
      source in pure water containing increasing concentrations of surfactants. The
      highest rising velocities were measured in pure water. Addition of surfactants
      caused a concentration-dependent and height-dependent decrease in bubble
      velocity; thus, bubbles are covered with surfactants as they rise, and the
      distance traveled until saturation is reached decreases with increased
      concentration of surfactant. Pluronic F68 is a potent effector of bubble
      saturation, 500 times more active than serum. At Pluronic F68 concentrations of
      0.1% (w/v), bubbles are saturated essentially at their source. The effect of
      bubble saturation on the interactions between animal cells and gas bubbles was
      investigated by using light microscopy and a micromanipulator. In the absence of
      surfactants, bubbles had a killing effect on cells; hybridoma cells and Chinese
      hamster ovary (CHO) cells were ruptured when coming into contact with a bubble.
      Bubbles only partially covered by surfactants adsorbed the cells. The adsorbed
      cells were not damaged and they also could survive subsequent detachment.
      Saturated bubbles, on the other hand, did not show any interactions with cells.
      It is concluded that the protective effect of serum and Pluronic F68 in sparged
      cultivation systems is based on covering the medium-bubble interface with
      surfaceactive components and that cell death occurs either after contact of cells
      with an uncovered bubble or by adsorption of cells through partially saturated
      bubbles and subsequent transport of cells into the foam region. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18615741
TI  - Monitoring recombinant inclusion body recovery in an industrial disc stack
      centrifuge.
AB  - A simple and rapid spectrophotometric method for measuring recombinant inclusion
      body concentrations in the presence of Escherichia coli cell debris has been
      applied to monitoring the performance of an industrial disc stack centrifuge.
      Turbidimetric measurements were made at two wavelengths, i.e., 600 nm and 420 nm,
      and the ratios of OD(600nm)/OD(420nm) related to the particle composition in
      suspension. The principle behind the technique is that inclusion body particles
      scatter light at 600 nm more effectively than do smaller cell debris particles
      when compared with the degree of light scatter at 420 nm. This technique may have
      broad potential application in developing an automatic monitoring and control
      system for industrial-scale inclusion body recovery. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615742
TI  - Model of the anaerobic metabolism of the biological phosphorus removal process:
      Stoichiometry and pH influence.
AB  - In the anaerobic phase of a biological phosphorus removal process, acetate is
      taken up and converted to PHB utilizing both energy generated in the degradation
      of polyphosphate to phosphate, which is released, and energy generated in the
      conversion of glycogen to poly-beta-hydroxy butyrate (PHB). The phosphate/acetate
      ratio cannot be considered a metabolic constant, because the energy requirement
      for the uptake of acetate is strongly influenced by the pH value. The observed
      phosphate/acetate ratio shows a variation of 0.25 to 0.75 P-mol/C-mol in a pH
      range of 5.5 to 8.5. It is shown that stored glycogen takes part in the
      metabolism to provide reduction equivalents and energy for the conversion of
      acetate to PHB. A structured metabolic model, based on glycogen as the source of
      the reduction equivalents in the anaerobic phase and the effect of the pH on the
      energy requirement of the uptake of acetate, is developed. The model explains the
      experimental results satisfactorily. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615743
TI  - Studies on microbial chromate reduction by Pseudomonas Sp. In aerobic continuous
      suspended growth cultures.
AB  - Reduction of hexavalent chromium was studied in three bench-scale continuous
      stirred tank reactors. The inoculum was a culture of Pseudomonas sp., capable of
      giving 83% to 87% chromate reduction in 72-h batch assays with 60 mg Cr(VI) L(-1)
      in synthetic medium. The continuous culture studies were conducted for about 100
      days using synthetic feed containing different levels of chromate (5 to 124 mg L(
      1)) at 28 degrees to 30 degrees C and pH 6.8. The feed rate was varied over the
      range 0.5 to 1 L d(-1) to obtain hydraulic retention time of 36 to 72 h. Chromate
      reduction efficiency was 81% to 91% and 100% for influent Cr(VI) concentrations
      of 15 to 124 and 5 mg L(-1), respectively, with a hydraulic retention time of 72
      h. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615744
TI  - Measurement of k(L)a by dynamic pressure method in pilot-plant fermentor.
AB  - The dynamic pressure method (DPM) is used for measurement of k(L)a in a 1-m(3)
      pilot scale fermentor in coalescing (distilled water) and noncoalescing (0.3 M
      Na(2)SO(4) aqueous solution) batches. The method consists in recording oxygen
      concentration in a batch after a small pressure change (20 kPa) in the fermentor.
      The upward pressure change is brought about by temporary closing and subsequent
      throttling of outlet gas stream and the downward change by full reopening of the
      gas outlet. Absorption of pure oxygen yields the same k(L)a values as absorption
      of air. In noncoalescing batch, the downward k(L)a values are always higher than
      the upward values owing to spontaneous nucleation of bubbles. The experiments
      performed in a stirred cell confirm this behavior. Thus, only upward pressure
      change should be used for measurement. The correlation of k(L)a data measured in
      small (18-L) and large (1000-L) vessels based on power dissipated and superficial
      gas velocity are in a good agreement. Unlike the DPM, the classical dynamic
      methods yield, under the same conditions, excessively low values of k(L)a (the
      dynamic startup method) or fail to produce data at all (the dynamic method with
      interchange of air for N(2)). (c) 1994 John Wiley & Sons, Inc.

PMID- 18615746
TI  - Multifactorial experimental design for optimizing transformation: Electroporation
      of Streptococcus thermophilus.
AB  - A multifactorial process was used to optimize transformation of Streptococcus
      thermophilus by electroporation. Simple experimental designs were applied to
      study three, four, or five factors in eight experiments. Four qualitative
      factors, growth and recovering media, and plasmid and bacterial strains, were
      studied empirically. Eight quantitative factors, including electrical,
      physiological, and chemical parameters, were studied by fractional factorial
      designs. Effects of individual parameters as well as interactions between them
      were investigated and optimized. Optimization was performed for one S.
      thermophilus strain, ST11, and proved to work for all other tested strains of the
      same species. Transformation efficiencies of 9 x 10(2) to 6 x 10(5) transformants
      per microgram DNA were achieved, depending on the strains and vectors used. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18615745
TI  - A prototype neural network supervised control system for Bacillus thuringiensis
      fermentations.
AB  - This article discusses the development of a prototype neural network-based
      supervisory control system for Bacillus thuringiensis fermentations. The input
      pattern to the neural network included the type of inoculum, operation
      temperature, pH value, accumulated process time, optical density in fermentation
      medium, and change in optical density. The output from the neural network was the
      predicted optical density for the next sampling time. The control system has been
      implemented in both a computer simulation and a laboratory fermentation
      experiment with promising results. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615747
TI  - Continuous reaction-separation process for enzymatic esterification in
      supercritical carbon dioxide.
AB  - The study of enzymatic esterification by an immobilized lipase in supercritical
      carbon dioxide (SCCO(2)) and in n-hexane, described in our previous works, was
      extended to continuous operation in a tubular fixed bed. The modeling of the
      reaction vessel operation was achieved through the use of the simple plug flow
      model coupled with the appropriate kinetic equation. Comparison with experiments
      proved to be satisfactory. The study of the postreactional separation, an
      important feature when using SCCO(2), was undertaken experimentally and good
      selectivities and product recovery were obtained. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18615748
TI  - Ammonia affects the glycosylation patterns of recombinant mouse placental
      lactogen-I by chinese hamster ovary cells in a pH-dependent manner.
AB  - The N-linked glycosylation of the recombinant protein mouse placental lactogen-I
      (mPL-I) expressed by Chinese hamster ovary (CHO) cells under nongrowth conditions
      was inhibited by increasing levels of ammonium chloride (3 and 9 mM) in a serum
      free, protein expression medium. The effect of ammonia on glycosylation was
      dependent on the extracellular pH (pH(e)). In media containing 0 and 9 mM
      ammonium chloride, the percentage of the most heavily glycosylated forms of
      secreted mPL-I decreased from ca. 90% to ca. 25% at pH(e) 8.0, and from ca. 90%
      to ca. 65% at pH(e) 7.6, respectively. However, at pH(e) 7.2, the most heavily
      glycosylated forms of secreted mPL-I decreased from ca. 90% to ca. 80% in media
      containing 0 and 9 mM ammonium chloride, respectively. Inhibition of mPL-I
      glycosylation was found to correlate with the calculated concentrations of the
      ammonia species (NH(3)). Control experiments showed that the ammonia effect on
      mPL-I glycosylation could not be attributed to increased chloride concentration
      or osmolarity, or to extracellular events after secretion of the recombinant
      protein into the supernatant. Ammonium chloride, 9 mM, inhibited the expression
      rate of MPL-I by CHO cells at low pH(e). (c) 1994 John Wiley & Sons, Inc.

PMID- 18615749
TI  - Transition state stabilization of subtilisins in organic media.
AB  - Electrostatic forces are among the stabilizing interactions that contribute to
      the high degree of enzyme-transition state complementarity. The active-site
      polarity, which can differ substaintially from that of water, is thus an
      important determinant of transition state stabilization. Here we pose the
      question of whether the rate of an enzymatic reaction proceeding through a
      charged transition state can be increased by increasing the active-site polarity
      in an organic solvent. The active-site polarity of subtilisin has been reduced by
      dehydration and suspension in a nonpolar solvent (tetrahydrofuran), and then
      increased by adding water to the solvent. Enhancing the local polarity
      substantially increasing the rate of catalysis, implicating polarity as an
      important factor in stabilizing the charged tetrahedral transition state. Studies
      with subtilisins whose active sites have been modified by site-directed
      mutagenesis support the role of polarity in transition state stabilization. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18615750
TI  - Biological destruction of CCl(4): I. Experimental design and data.
AB  - A denitrifying consortium capable of transforming carbon tetrachloride (CCl(4))
      was cultured from aquifer sediment from the U.S. Department of Energy's Hanford
      Site in southeastern Washington State. To understand the kinetics of the
      biological destruction of CCl(4) by these microbes, a set of experiments, the
      conditions of which were chosen according to a fractional factorial experimental
      design, were completed. This article reports on the experimental design along
      with the results for CCl(4), biomass, acetate, nitrate, and nitrite
      concentrations. These data indicate that growth is inhibited by high nitrite
      concentrations, whereas CCl(4) degradation is slowed by the presence of nitrate
      and/or nitrite. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615753
TI  - Preface. Tissue engineering and cell therapies.

PMID- 18615751
TI  - Mechanism of extraction of chymotrypsin into isooctane at very low concentrations
      of aerosol OT in the absence of reversed micelles.
AB  - Chymotrypsin is easily extracted from an aqueous solution into isooctane
      containing the anionic surfactant aerosol OT (AOT). The concentration of AOT
      needed to efficiently extract 0.5 mg/mL CMT is as low as 1 mM and as low as 0.2
      mM AOT was sufficient to extract the protein into isooctane. The extraction
      process was unaffected by 10% (v/v) ethyl acetate in the isooctane phase.
      Moreover, spectroscopic analysis by electron paramagnetic resonance indicated
      that CMT did not exist inside a discreet water pool of a reversed micelle.
      Calculations of the number of AOT molecules associated per extracted CMT molecule
      indicate that only ca. 30 surfactant molecules interact with the protein, a value
      too low for reversed micellar incorporation of the protein in isooctane. These
      studies suggested that reversed micelles do not need to be involved in the actual
      transfer of the protein from the aqueous to the organic phase and protein
      solubilization in the organic phase is possible in the absence of reversed
      micelles. Based on these findings, a new mechanism has been proposed herein for
      protein extraction via the phase transfer method involving ionic surfactants. The
      central theme of this mechanism is the formation of an electrostatic complex
      between CMT and AOT at the aqueous/organic interface between AOT and CMT, thereby
      leading to the formation of a hydrophobic species that partitions into the
      organic phase. Consistent with this mechanism, the efficiency of extraction is
      dependent on the interfacial mass transfer, the concentrations of CMT and AOT in
      the aqueous and organic phases, respectively; the ionic strength of the aqueous
      phase; and the presence of various cosolvents. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615754
TI  - Review: Tissue engineering in the nervous system.
AB  - The nervous system presents a challenge to the field of tissue engineering
      because some of its complex neurochemical and neuroanatomical architecture is
      just beginning to be understood. A combination of advances in molecular
      neurobiology, gene transfer techniques, and the concomitant advances in the
      engineering of biomaterials at a molecular level, are making tissue engineering
      in the nervous system possible. Due to the vast range of fields that this highly
      interdisciplinary task spans, any review is bound to be somewhat limited. Given
      that, this review attempts to cover some solutions engineered for: (a) the
      functional replacement of a missing neuroactive component; (b) the rescue or
      regeneration of degenerated neural tissue; and (c) the building of intelligent
      neural cell-based biosensors and simple in vitro neural circuits based on
      controlled neural cell attachment to electrically relevant substrates. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18615755
TI  - Cell aggregation and neurite growth in gels of extracellular matrix molecules.
AB  - Components of the extracellular matrix are believed to guide both nerve cells and
      neurites to their targets during embryogenesis and, therefore, might be useful
      for controlling regeneration of nervous tissue in adults. To study the influence
      of extracellular conditions on neurite outgrowth and cell motility, PC12 cells
      were suspended in three-dimensional gels containing (i) collagen (0.4 to 2
      mg/mL), (ii) collagen (1 mg/mL) with added fibronectin or laminin (1 to 100
      mug/mL), and (iii) agarose (7 mg/mL) with added collagen (0.001 to 1 mg/mL).
      Neurite outgrwoth was stimulated with nerve growth factor (NGF) and both the
      extent of neurite outgrowth ad cell aggregation were quantitated over 10 to 12
      days in culture. The extent of neurite outgrowth was greatest at the lowest
      collagen concentration tested (0.4 mg/mL) and decreased with increasing
      concentration. The addition of laminin or fibronectin altered the extent of
      neurite outgrowth in collagen gels, but the differences were small. Although no
      neurite growth was observed in pure agarose gels, considerable neurite outgrowth
      occurred with the addition of small amounts (>/=0.01 mg/mL) of collagen. Mean
      aggregate size increased more quickly in gels with lower concentrations of
      collagen. For cells in 1.0 mg/mL collagen, a four- to fivefold increase in
      aggregate volume was seen between days 2 and 10 o the culture period, whereas the
      increase in DNA content during this same period was less than twofold, suggesting
      that the cells were aggregating, not multiplying. These results suggest that the
      composition of the matrix supporting nerve cells has a significant effect on both
      neurite outgrowth and cell motility. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615756
TI  - Poly(ethylene oxide)-grafted thermoplastic membranes for use as cellular hybrid
      bio-artificial organs in the central nervous system.
AB  - Poly(acrylonitrile-co-vinyl chloride) (PAN/VC) anisotropic membranes were
      chemically modified with poly(ethylene oxide) (PEO) (5000 and 20,000 g/mol) by
      one of two aqueous reactions: (a) acid hydrolysis of the nitrile group to a
      carboxylic acid with which amine-terminated PEO (PEO-NH(2)) reacted or (b) base
      reduction of the nitrile group to an amine with which PEO-succinimide (PEO-SC)
      reacted. Approximately 1.3% of the bulk material was modified with PEO-NH(2)
      whereas 1.8 to 3.5% was modified with PEO-SC as determined by proton nuclear
      magnetic resonance ((1)H NMR) and attenuated total reflectance Fourier transform
      infrared (ATR FTIR) spectra. Approximately 50 to 75% less bovine serum albumin
      (BSA) adsorbed to PEO-grafted single skin fibers than to unmodified PAN/VC.
      Transport properties of modified and unmodified fibers were compared by passive
      diffusion, convective nominal molecular weight cutoff, and hydraulic
      permeability. Neither hydraulic permeability nor nominal molecular weight cutoff
      of BSA changed appreciably after surface modification with PEO indicating that
      pore structure was not adversely affected by the chemistry involved in grafting
      poly(ethylene oxide). However, in the absence of any membrane conditioning, the
      apparent diffusion of alpha-chymotrypsinogen (24,000 g/mol) was enhanced in PEO
      grafted PAN/VC fibers possibly as a result of reduced sorption of the permeating
      protein. In vivo biocompatibility in the brain tissue of rats was judged by
      histological assessment of the host's cellular response to fibers implanted for
      30 days; biocompatibility of both PAN/VC and PAN/VC-g-PEO was satisfactory but
      improved slightly with PEO grafting. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615757
TI  - Mini-review: Osteoblasts: An in vitro model of bone-implant interactions.
AB  - Well-characterized osteoblasts provide a successful in vitro model to study bone
      biomaterial interactions. Knowledge of the events occurring at this tissue
      biomaterial interface could lead to the design of improved orthopedic/dental
      biomaterials which elicit specific and desirable responses from surrounding
      cells/tissues, optimize function of osteoblasts (the boneforming cells), and
      enhance long-term bone-implant bonding. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615758
TI  - Homogenization theory and digital imaging: A basis for studying the mechanics and
      design principles of bone tissue.
AB  - Bone tissue is a complex multilevel composite which has the ability to sense ad
      respond to its mechanical environment. It is believed that bone cells called
      osteocytes within the bone matrix sense the mechanical environment and determine
      whether structural alterations are needed. At present it is not known, however,
      how loads are transferred from the whole bone level to cells. A computational
      procedure combining representative volume element (RVE) based homogenization
      theory with digital imaging is proposed to estimate strains at various levels of
      bone structure. Bone tissue structural organization and RVE based analysis are
      briefly reviewed. The digital image based computational procedure was applied to
      estimate strains in individual trabeculae (first-level microstructure).
      Homogenization analysis of an idealized model was used to estimate strains at one
      level of bone structure around osteocyte lacunae (second-level trabecular
      microstructure). The results showed that strain at one level of bone structure is
      amplified to a broad range at the next microstructural level. In one case, a zeor
      level tensile principal strain of 495 muE engendered strains ranging between 
      1000 and 7000 muE in individual trabeculae (first-level microstructure).
      Subsequently, a first-level tensile principal strains of 1325 muE within an
      inidividual trabecula engendered strains ranging between 782 and 2530 muE around
      osteocyte lacunae. Lacunar orientation was found to influence strains around
      osteocyte lacunae much more than lacunar ellipticity. In conclusion, the
      computational procedure combining homogenization theory with digital imaging can
      proveide estimates of cell level strains within whole bones. Such results may be
      used to bridge experimental studies of bone adaptation at the whole bone and cell
      culture level. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615759
TI  - Kinetics of chondrocyte growth in cell-polymer implants.
AB  - In vitro cultivation of cartilage cells (chondrocytes) on biodegradable
      polyglycolic acid (PGA) scaffolds resulted in implants which could potentially be
      used to repair damaged joint cartilage or for reconstructive surgery. Cell growth
      kinetics were studied to define conditions under which the cellularity of
      implants made from isolated calf chondrocytes reached that of the parent calf
      cartilage. In static cultures, condrocyte growth rates decreased as either
      implant thickness or implant cell density increased. Over 4 weeks of cultivation,
      implant permeability to glucose decreased to 3% that of the plain polymer
      scaffold; this effect was attributed to the decrease in effective implant
      porosity associated with cartilage tissue regeneration.In a well-mixed culture,
      implants 1 cm in diameter by 0.3 cm thick maintained high cell growth rates over
      7 weeks and hard normal cell densities. Regenerated cartilage with these
      dimensions is large enough to resurface small joints such as the trapezium bone
      at the base of the human thumb. Such implants could not be grown statically,
      since cell growth stopped at 3-4 weeks and cell densities remained below normal.
      Optimization of the tissue culture environment is thus essential in order to
      cultivate clinically useful cartilage implants in vitro. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18615760
TI  - Composition of cell-polymer cartilage implants.
AB  - Cartilage implants for potential in vivo use for joint repair or reconstructive
      surgery can be created in vitro by growing chondrocytes on biodegradable polymer
      scaffolds. Implants 1 cm in diameter by 0.176 cm thick were made using isolated
      calf chondrocytes and polyglucolic acid (PGA). By 6 weeks, the total amount of
      glycosaminoglycan (GAG) and collagen (types I and II) increased to 46% of the
      implant dry weight; there was a corresponding decrease in the mass of PGA.
      Implant biochemical and histological compositions depended on initial cell
      density, scaffold thickness, and the methods of cell seeding and implant culture.
      Implants seeded at higher initial cell densities reached higher GAG contents
      (total and per cell), presumably due to cooperative cell-to-cell interactions.
      Thicker implants had lower GAG and collagen contents due to diffusional
      limitations.Implants that were seeded and cultured under mixed conditions grew to
      be thicker and more spatially uniform with respect to the distribution of cells,
      matrix, and remaining polymer than those seeded and/or cultured statically.
      Implants from mixed cultures had a 20-40-mum thick superficial zone of flat cells
      and collagen oriented parallel to the surface and a deep zone with perpendicular
      columns of cells surrounded by GAG Mixing during cell seeding and culture
      resulted in a more even cell distribution ad enhanced nutrient diffusion which
      could be related to a more favorable biomechanical environment for
      chondrogenesis. Cartilage with appropriate for and function for in vivo
      implantation ca thus be created by selectively stimulating the growth and
      differentiated function of chondrocytes (i.e., GAG and collagen synthesis)
      through optimization of the in vitro culture environment. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18615761
TI  - Modulation of secretion of vasoactive materials from human and bovine endothelial
      cells by cyclic strain.
AB  - The effects of cyclical expansion and elaxation of the vessel wall on endothelial
      cell metabolism have been modeled using a uniaxial strain device and cultured
      endothelial cell monolayers. Also, the effects of stopping and then restarting
      cyclic strain on metabolite secreation rates were determined. Secretion rates of
      prostacyclin (PGI(2)), endothelin, tissue plasminogen activator (t-PA), and
      plasminogen activator inhibitor-type 1 (PaI-1) by endothelial cells were constant
      over24-h periods The secreation of both PGI(2) and endothelin was enhanced in
      cells exposed to high physiological levels of cyclical strain (10% at 1Hz)
      compared with controls, while tPA production was unaltered. These results were
      true for both human and bovine endothelial cells. Characterization of the
      response of human endothelial cells to cyclical strain made evaluation of stretch
      effects on PAl-1 secretion possible. A nearly twofold increase in PAl-1 secretion
      by cells exposed to arterial levels of strain was observed. Endothelin secretion
      remained elevated even after strain was stopped for 12 h, while PGl(2) secretion
      returned to control values upon cessation of cyclic stretch. These results
      indicate that physiological levels of cyclic mechanical strain ca significantly
      modulate secretion of vasoactive metabolited form endothelial cells. The changes
      sen secretion are, in some cases, quite different from those caused by arterial
      levels of fluid shear stress exposure. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615762
TI  - Analysis of endothelial cell locomotion: Differential effects of motility and
      contact inhibition.
AB  - Video microscopy and digital time-lapse recording were used to monitor locomotion
      and proliferation of bovine pulmonary artery endothelial (BPAE) cells cultured
      with varying concentrations of basic fibroblast growth factor (bFGF). Cell
      trajectories were reconstructed using a generalized nearest-neighbor algorithm
      and analyzed to determine how cell motility is affected by cell-cell collisions,
      cell divisions, and increasing cell density. The temporal evolution patterns of
      the average speed of locomotion for all cells in a culture were computed and the
      effects of varying bFGF concentrations were analyzed. Intermediate concentrations
      of bFGF (30 and 50 ng/mL) significantly increased the speed of locomotion above
      the levels we observed with 0 and 100 ng/mL concentrations of bFGF. Increases in
      cell density due to proliferation were immediately accompanied by a decrease in
      the average speed of locomotion of the cell population. Finally, the effect of
      bFGF concentration on the overall cell proliferation rates was assessed. With the
      addition of 30 or 50 ng/mL of bFGF to the culture media, the observed cell
      proliferation rates increased significantly. The proliferation rates decreased
      when the bFGF concentration increased to 100 ng/mL. These results show that bFGF
      concentrations that increase the motility of BPAE cells also increase the
      observed cell proliferation rates. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615763
TI  - Long-Term continuous culture of hepatocytes in a packed-bed reactor utilizing
      porous resin.
AB  - As part of our attempt to develop a hybrid artificial liver support system using
      cultured hepatocytes, we investigated the long-term metabolic function of
      hepatocytes incubated in a packed-bed type reactor using reticulated polyvinyl
      formal (PVF) resin as a supporting material. Long-term (up to 1 week) perfusion
      culture experiments using the packed-bed reactor (20 mm i.d.) loaded with 500 PVF
      resin cubes (mean pore size 250 mum, 2 x 2 x 2 mm), together with conventional
      monolayer culture experiments as controls, were performed in serum-free or serum
      containing medium. Ammonium metabolism and urea synthesis activities were
      evaluated quantitatively based on reaction kinetic analyses. Initial rates of
      ammonium metabolism and urea-N synthesis, as well as GPT enzyme activities, were
      adopted as indexes of the metabolic performance of the reactor and activities of
      the cultured hepatocytes.When serum-free medium was used in the perfusion
      cultures, ammonium metabolic and urea-N synthetic rates showed significant decay
      with elapse of the culture period, being less than 10% of those measured on day
      1. This loss of activity was more prominent in the perfusion culture than in the
      monolayer cultures using this medium. In contrast, when serum-containing medium
      was used, approximately 50% of these activities obtained on day 1 were maintained
      even at the end of the cultures both in the perfusion and monolayer culture
      experiments.We concluded that the packed-bed reactor using PVF resin enabled high
      density culture of hepatocytes, and showed a satisfactory ability to maintain the
      metabolic function of immobilized hepatocytes for relatively long periods of up
      to 1 week. This type of reactor is thus considered to represent a breakthrough in
      overcoming the difficulties involved in the development of a hybridtype
      artificial liver support system. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615764
TI  - Isolated hepatocytes in a bioartificial liver: A single group view and
      experience.
AB  - Despite recent advances in medical supportive therapy, patients with severe
      fulminant hepatic failure (FHF) have mortality rate approaching 90%.
      Investigators have attempted to improve survival by using various extracorporeal
      liver support systems loaded with sorbents and liver tissue preparations. None of
      them succeeded in gaining clinical acceptance and orthotopic liver
      transplantation (OLT) remains a primary therapeutic option for patients with FHF.
      In this study, authors discuss the systems which utilize isolated hepatocytes.
      Most of these devices were tested in vitro and in animals with chemically and
      surgically induced liver failure. In some studies, signficant levels of
      detoxification and liver functions were achieved. The authors describe their own
      hepatocyte-based artificial liver (BAL). It is based on plasma perfusion through
      a hollow-fiber module seeded with matrix-anchored porcine hepatocytes. The BAL
      was used 14 times to treat 9 patients with acute liver failure. On 10 occasions,
      a charcoal column was included in the plasma circuit. Each treatment lasted 7 +/-
      1 h. All procedures were tolerated well and 8 patients (including 6 patients with
      FHF) underwent OLT. Five patients with increased intracranial pressure (ICP) and
      evidence of decerebration had normalization of ICP and enjoyed full neurologic
      recovery after OLT. Laboratory data showed evidence for bilirubin conjugation,
      decrease in blood ammonia, maintenance of low lactic acid levels, and increase in
      the ration between the branched chain and aromatic amino acids. No allergic
      reactions to xenogeneic hepatocytes were observed. The authors conclude that BAL
      treatment with porcine hepatocytes appears to be safe and can help maintain
      patients alive and neurologically intact until a liver becomes available for
      transplantation. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615765
TI  - Oxygen is a factor determining in vitro tissue assembly: Effects on attachment
      and spreading of hepatocytes.
AB  - Many recent studies related to the development of bioartificial liver devices
      have utilized hepatocytes cultured within devices of various geometries. Because
      hepatocytes are anchorage-dependent cells, they need to attach and spread onto
      the extracellular matrix to be able to function, a process that requires energy.
      Thus, it is important to deliver enough oxygen to hepatocytes contained within
      bioartificial liver devices during the early phase of cellular organization while
      the cells interact with the extracellular matrix. In this study, we investigated
      the effect of oxygen on the attachment and spreading of hepatocytes. Increasing
      the gas phase oxygen from 0 to 160 mmHg resulted in an increase in the percentage
      of cells attaching from 43.0 +/- 5.8% to 103.6 +/- 29%, 1 h after seeding. In a
      similar manner, increasing the gas phase oxygen from 0 to 160 mmHg resulted in an
      increase of the projected surface area from 310 +/- 35 to 827 +/- 127 mum(2), 24
      h after seeding. Furthermore, the partial pressure of oxygen at the cell level
      was estimated using a diffusion-reaction model. The model indicated that a cell
      surface oxygen partial pressure of 0.064 mmHg was required for the half-maximal
      (K(m) (a)) attachment of hepatocytes to collagen-based substrate. On the other
      hand, the K(m) (s) value of the spreading process was predicted to be 0.13 mmHg.
      The results of this study demonstrate the importance of oxygen during the initial
      stages of attachment and spreading of hepatocytes, and it has important
      implications in the design of hepatocyte-based bioartificial liver devices. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18615766
TI  - Engineering organ perfusion protocols: NMR analysis of hepatocyte isolation from
      perfused rat liver.
AB  - The development and use of an extracorporeal liver support device depends upon
      the isolation of a large number of viable, functioning hepatocytes from whole or
      partial livers. Current practice, however, produces nonoptimal yields, given that
      a large percentage of hepatocytes initially present are not successfully
      isolated. The normal hepatocyte isolation protocol consists of sequential
      perfusion with calcium chelating and collagenase buffers, and then separation of
      viable hepatocytes from non-viable and nonparenchymal cells, usually on the basis
      of cell density. In order to improve understanding regarding the metabolic and
      perfusion state of the liver during this perfusion protocol, ATP, pH, and tissue
      perfusion were evaluated using nuclear magnetic resonance (NMR). Perfusion with
      calcium chelating buffer was found to have minimal effect on the metabolic and
      perfusion parameters, whereas subsequent perfusion with collagenase buffer
      produced large declines in ATP, pH, and homogeneity of perfusion within 3 min.
      Perfusion with calcium-chelating buffer alone, or perfusion with calcium
      chelating buffer followed by a short period of ischemia to mimic the perfusion
      disruption of collagenase, did not produce the same decline in metabolic
      parameters. This NMR data suggested that enhancing the early perfusion and
      penetration of collagenase or prolonging the nontoxic calcium-chelation step may
      improve the yield and/or functionality of isolated cells. Therefore, several
      altered perfusion protocols were evaluated in terms of yield of viable
      parenchymal hepatocytes and hepatocyte albumin production. Although increasing
      the perfusion flow rate and initial perfusion with inactive (cold) collagenase
      did not produce significant improvements when compared with the control protocol
      (control cell yield 226 +/- 42 x 10(6) viable hepatocytes for 10- to 14-week-old
      female Lewis rat), prolonging and enhancing the calcium-chelating perfusion step
      or increasing the collagenase concentration did yield a significantly great
      number of viable parenchymal hepatocytes (393 +/- 44 and 328 +/- 39 x 10(6)
      viable hepatocytes, respectively) with no change in albumin production per seeded
      viable cell. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615767
TI  - Mini-review: Islet transplantation to create a bioartificial pancreas.
AB  - Donor scarcity precludes the use of pancreatic transplantation to treat type I
      diabetes. Xenogeneic islet transplantation offers the possibility of overcoming
      this problem; however, it entails the use of immunoisolation devices to prevent
      immune rejection of the transplanted islets. These devices consist of a
      semipermeable membrane, which surrounds the islets and isolates them from the
      host's immune system, while allowing the passage of insulin and essential
      nutrients, including glucose. Problems associated with proposed device designs
      include diffusion limitations, biocompatibility, device retrieval in the event of
      failure, and mechanical integrity. Microencapsulation appears to be the most
      promising system of immunoisolation, however, the design of a device suitable for
      human clinical use remains a challenge. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615768
TI  - Tissue engineering of a bioartificial kidney.
AB  - Tissue engineering is a rapidly growing field in biotechnology. The use and
      packaging of synthetic materials, biologic compounds, and cellular components of
      specific tissues can be envisioned to replace physiologic function of diseased
      organs. Long-term ex vivo therapy for kidney failure has been achieved, so that
      the kidney may be the first solid organ in which tissue engineering concepts can
      produce an implantable device for long-term in vivo replacement therapy. To
      replace the kidney's excretory function, an implantable bioartificial kidney
      requires both a device to replace blood ultrafiltration performed by renal
      glomeruli and a device to replace transport regulatory function of the renal
      tubule. The initial concepts for these devices are just beginning to be
      considered and developed. (c) 1994 John Wiley & Sons, Inc.

PMID- 18615769
TI  - Semiconductor wires and ribbons for high-performance flexible electronics.
AB  - This article reviews the properties, fabrication and assembly of inorganic
      semiconductor materials that can be used as active building blocks to form high
      performance transistors and circuits for flexible and bendable large-area
      electronics. Obtaining high performance on low temperature polymeric substrates
      represents a technical challenge for macroelectronics. Therefore, the fabrication
      of high quality inorganic materials in the form of wires, ribbons, membranes,
      sheets, and bars formed by bottom-up and top-down approaches, and the assembly
      strategies used to deposit these thin films onto plastic substrates will be
      emphasized. Substantial progress has been made in creating inorganic
      semiconducting materials that are stretchable and bendable, and the description
      of the mechanics of these form factors will be presented, including circuits in
      three-dimensional layouts. Finally, future directions and promising areas of
      research will be described.

PMID- 18615770
TI  - Clinical-grade preparation of human natural regulatory T-cells encoding the
      thymidine kinase suicide gene as a safety gene.
AB  - BACKGROUND: Human CD4+CD25+FOXP3+ natural regulatory T-cells (nTreg) have a great
      therapeutic potential for the induction of tolerance in allo-transplanted
      patients or for the control of severe auto-immune diseases. However, clinical
      grade production of nTreg remains difficult to achieve because of the absence of
      a truly specific surface marker and of their low frequency that implies a need
      for their ex vivo expansion. Furthermore, safety issues should be taken into
      consideration due to the risk of either uncontrolled nTreg-induced
      immunosuppression or uncontrolled proliferation of autoreactive contaminating T
      cells particularly in an auto-immune context. METHODS: We compared different
      clinical-grade conditions for immuno-magnetic selection and ex vivo expansion of
      nTreg. For safety, expanded cells were genetically modified with retroviral
      vectors co-expressing human CD90 and HSV1 thymidine kinase. The CD90 surface
      marker and thymidine kinase allow for selection and elimination of transduced
      cells by ganciclovir, respectively. RESULTS: We showed that (i) nTreg could be
      enriched in a one step using CD25 microbeads, were functionally suppressive and
      mainly FOXP3+; (ii) using anti-CD28- and anti-CD3-coated beads, interleukin-2 and
      rapamycin, nTreg were expanded 150-200-fold after 3 weeks. Under these clinical
      grade conditions, they remained suppressive, and no major alteration of the TCR
      repertoire was observed; (iii) after efficient retroviral transduction and CD90
      selection, nTreg maintained their suppressive activity; (iv) transduced nTreg
      could be eliminated by ganciclovir upon activation. CONCLUSIONS: The efficient
      procedure reported here for the preparation of nTreg, whose safety has been
      ensured, is now applicable for further clinical trials.

PMID- 18615771
TI  - Live single-cell video-mass spectrometry for cellular and subcellular molecular
      detection and cell classification.
AB  - The molecular content from the cytoplasm of a live, single mammalian cell and its
      organelle were trapped with a nano-electrospray ionization (ESI) tip acting as a
      micropipette under a video microscope, and hundreds of small molecular peaks were
      detected by direct nano-ESI mass spectrometry (MS). Granule- or cytoplasm
      specific peaks in a mast cell (RBL 2H3) model were extracted by paired t-test to
      demonstrate their specific localization. Some of the typical and specific
      molecules were successfully identified by MS/MS analysis. This method was also
      applied to the cell classification of seven types of cell lines at the single
      cellular level by principal component analysis (PCA), revealing seven clusters in
      the multivariate score plot.

PMID- 18615772
TI  - The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene
      therapy of the prostate?
AB  - BACKGROUND: Radiation therapy is a treatment modality routinely used in cancer
      management so it is not unexpected that radiation-inducible promoters have
      emerged as an attractive tool for controlled gene therapy. The human tissue
      plasminogen activator gene promoter (t-PA) has been proposed as a candidate for
      radiogenic gene therapy, but has not been exploited to date. The purpose of this
      study was to evaluate the potential of this promoter to drive the expression of a
      reporter gene, the green fluorescent protein (GFP), in response to radiation
      exposure. METHODS: To investigate whether the promoter could be used for prostate
      cancer gene therapy, we initially transfected normal and malignant prostate
      cells. We then transfected HMEC-1 endothelial cells and ex vivo rat tail artery
      and monitored GFP levels using Western blotting following the delivery of single
      doses of ionizing radiation (2, 4, 6 Gy) to test whether the promoter could be
      used for vascular targeted gene therapy. RESULTS: The t-PA promoter induced GFP
      expression up to 6-fold in all cell types tested in response to radiation doses
      within the clinical range. CONCLUSIONS: These results suggest that the t-PA
      promoter may be incorporated into gene therapy strategies driving therapeutic
      transgenes in conjunction with radiation therapy.

PMID- 18615773
TI  - Adaptive or maladaptive response to adenoviral adrenomedullin gene transfer is
      context-dependent in the heart.
AB  - BACKGROUND: Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide
      produced in the heart, but controversy persists regarding its cardiac effects. We
      explored the potential role of AM on cardiac function and remodeling by direct
      recombinant adenoviral AM gene delivery into the anterior wall of the left
      ventricle (LV). METHODS: AM was overexpressed in healthy rat hearts and in hearts
      during the remodeling process in response to pressure overload and myocardial
      infarction. The AM effects were analysed with echocardiography and in an isolated
      perfused rat heart preparation. The expression of AM and the activation of
      underlying signaling pathways were also investigated. RESULTS: AM mRNA increased
      by 20.9-fold (p < 0.001) in healthy rat heart and improved fractional shortening
      by 14% (p < 0.05) and ejection fraction by 8% (p < 0.05). In isolated perfused
      hearts, an increase (p < 0.05) in the first derivative of isovolumic LV pressure
      rise (dP/dt(max)) without alteration in diastolic properties was noted. The
      overexpression of AM activated protein kinase Cepsilon and Cdelta isoforms in the
      LV, whereas p38 mitogen-activated protein kinase activity decreased. Angiotensin
      II-induced LV hypertrophy was significantly attenuated by AM (p < 0.01) without
      compromising cardiac contractility. By contrast, AM enhanced LV dilatation (p <
      0.01) and anterior wall thinning (p < 0.001) and augmented the deterioration of
      LV function (p < 0.05) post-infarction. CONCLUSIONS: The results obtained in the
      present study show that AM overexpression improves LV systolic function without
      altering cardiac diastolic properties in the normal heart. Moreover, AM is a
      potent context-dependent modulator of LV remodeling because it promotes an
      adaptive response in pressure overload-induced LV hypertrophy and triggers a
      maladaptive process in post-infarction remodeling.

PMID- 18615775
TI  - Theoretical and experimental study of tropylium formation from substituted
      benzylpyridinium species.
AB  - Fragmentation pathways of unsubstituted and substituted benzylpyridinium
      compounds were investigated using mass-analysed kinetic energy (MIKE) technique
      in combination with high level of quantum chemical calculations in the gas phase.
      Fast atom bombardment (FAB) source was used for ionisation of the studied
      compounds. The formation of both benzylium and tropylium species were
      investigated. Hybrid Hartree-Fock/Density Functional Theory calculations have
      been performed to assess the geometries and the energies of the transition states
      and intermediates. For each cases, different reaction pathways were investigated,
      and particularly in the case of the formation of tropylium species, the formation
      of the seven-membered ring before or after the loss of pyridine were studied. The
      effect of para-methyl and para-methoxy substituents on the activation energy of
      the rearrangement process to form thermodynamically stable tropylium compounds
      has been studied. Theoretical calculations showed competition between direct bond
      cleavage and rearrangement reactions to form benzylium and tropylium compounds,
      respectively. Experimental results also suggested that the rearrangement process
      takes place to yield stable tropylium under "soft ionisation techniques", such as
      FAB.

PMID- 18615776
TI  - The neuropsychological profile in dementia with Lewy bodies and Alzheimer's
      disease.
AB  - OBJECTIVE: To demonstrate the exact nature of the cognitive profile of dementia
      with Lewy bodies (DLB) on standardized neuropsychological tests including the
      Wechsler Adult Intelligence Scale--Revised (WAIS-R) and the Wechsler Memory Scale
      -Revised (WMS-R). DESIGN: We examined the WAIS-R and the WMS-R of 26 patients
      with probable DLB (based on the Consensus Criteria for the clinical diagnosis of
      DLB) and of 78 patients with probable Alzheimer's disease (AD) (based on criteria
      of the National Institute for Neurological and Communicative Disorders and Stroke
      Alzheimer's disease and Related Disorders Association) who were matched to the
      patients with DLB 3:1 by Mini-Mental State Examination score. RESULTS: The DLB
      group scored significantly lower on the Block Design, Object Assembly and Digit
      Symbol of WAIS-R and significantly higher on the Logical Memory I, Verbal Paired
      Associates I, Logical Memory II, Visual Paired Associates II, Verbal Paired
      Associates II and Visual Reproduction II of WMS-R (p < 0.0016 to p < 0.0001). In
      a comparison between the DLB group and the AD group, a logistic regression
      analysis revealed that the weighted sum score of the Object Assembly and the
      Logical Memory II may differentiate DLB from AD with a sensitivity of 0.81 [95%
      Confidence Intervals (CI) = 0.66-0.96] and a specificity of 0.76 (95% CI = 0.66
      0.85). CONCLUSIONS: The WAIS-R and the WMS-R can help to differentiate DLB from
      AD.

PMID- 18615774
TI  - New approaches to the treatment of human herpesvirus 8-associated disease.
AB  - Human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus
      or KSHV) is the etiologic agent of Kaposi sarcoma (KS) and primary effusion
      lymphoma (PEL), as well as many cases of Castleman disease. Despite significant
      advances in understanding the biology and natural history of these diseases,
      current treatment options have important limitations, and strategies to prevent
      their development in high-risk individuals are lacking. This article reviews the
      scope of HHV-8-associated disease, as well as the efficacy of current treatment
      options. Finally, novel approaches to treatment and prevention are described,
      including antiviral agents, targeted molecular therapy and a combination of these
      modalities.

PMID- 18615777
TI  - Reproducible methodology for the isolation of mesenchymal stem cells from human
      umbilical cord and its potential for cardiomyocyte generation.
AB  - Mesenchymal stem cells (MSCs) are considered to be a source of stem cells in
      tissue regeneration and therapeutics, due to their ability to undergo
      proliferation and differentiation. Complications associated with bone marrow
      derived MSCs has prompted researchers to explore alternative sources of MSCs. The
      human umbilical cord is one such source; it is easily available and its
      collection is non-invasive. The sources of MSCs are non-controversial and thus
      they are not subjected to ethical constraints, as in the case of embryonic stem
      cells. MSCs are multipotent stem cells and has the ability to differentiate into
      various cell types of the mesodermal lineage. The aim of this study was to
      establish a reproducible method for the isolation of MSCs from human umbilical
      cord, as the few methods published till date gave inconsistent results and had a
      mixed population of contaminating endothelial cells. In our isolation strategy,
      we isolated a pure population of MSCs from Wharton's jelly of the human umbilical
      cord, which is very rich in collagen, and we used a high concentration of
      collagenase enzyme in the isolation of MSCs. Extensive phenotypic
      characterization analysis of these cells, using flow cytometry and antibody
      staining methods, have shown that we were able to isolate a pure population of
      the mesenchymal lineage cells that is devoid of haematopoietic and endothelial
      cell contaminants. When these MSCs were subjected to cardiomyocyte
      differentiation, we observed a change in the morphological characteristics, which
      was accompanied by the formation of myotube structures and spontaneous beating
      after 21 days.

PMID- 18615778
TI  - Chitosan microparticles as injectable scaffolds for tissue engineering.
AB  - The use of chitosan microparticles as injectable carriers for cell
      transplantation represents a promising alternative to avoid the drawbacks of the
      implantation of other forms of three-dimensional (3D) scaffolds seeded with
      cells. In this study, a 3D construct is obtained in vitro by combining chitosan
      microparticles crosslinked with genipin and goat bone marrow stromal cells
      (GBMCs). Cell viability and the morphology of GBMCs were evaluated after culture
      for 7 and 14 days. Our results show the feasibility of chitosan microparticles as
      potential injectable scaffolds for tissue engineering and regenerative medicine.

PMID- 18615780
TI  - Validation of the Arabic version of the 5-item WHO Well Being Index in elderly
      population.

PMID- 18615779
TI  - Validity and reliability of the Simpson-Angus Scale (SAS) in drug induced
      parkinsonism in the elderly.
AB  - BACKGROUND: Quantification of drug induced parkinsonism (DIP) for study purposes
      is difficult. The most often used Simpson Angus Scale (SAS) lacks proper
      clinimetric evaluation. The newer Schedule for Assessment of Drug-Induced
      Movement Disorders (SADIMoD) shows good clinimetric characteristics, but has not
      been used in published clinical studies, probably due to the complexity of the
      scale. OBJECTIVES: To evaluate internal consistency and inter-rater reliability
      of the SAS and the correlation ot f the SAS with the parkinsonism subscale of the
      SADIMoD in elderly. METHOD: Fifteen elderly diagnosed with DIP were recruited.
      The patients were assessed three times with the SAS by three independent
      investigators. The resident also performed the SADIMoD. Internal consistency was
      measured by Cronbach's alpha-coefficient, inter-rater variability was examined
      with weighted kappa values and percentage of agreement and correlation to SADIMoD
      by Spearman's correlation coefficient. RESULTS: SAS demonstrated good internal
      consistency reliability (Cronbach's alpha coefficients 0.83). Inter-rater
      reliability for sum score was good. For individual items slight agreement on the
      item salivation and moderate to very good agreement on remaining items calculated
      by weighted kappa values was reached. We found 87-100% agreement on the
      individual items with acceptance of 1 point difference between raters. The SAS
      demonstrated acceptable correlation with the SADIMoD parkinsonism subscale scores
      (Spearman's rho = 0.66; p < 0.01). CONCLUSION: The SAS appears to be a valid and
      by different instructed health care professionals easy to perform research tool
      to evaluate DIP.

PMID- 18615781
TI  - Effects of Alzheimer's disease and mild cognitive impairment on driving ability:
      a controlled clinical study by simulated driving test.
AB  - OBJECTIVE: To assess the effects of Alzheimer's disease (AD) and Mild Cognitive
      Impairment (MCI) on simulated car driving ability. METHODS: Twenty patients with
      a probable AD of mild severity (Clinical Dementia Rating, CDR = 1) were compared
      with 20 subjects with MCI (CD = 0.5), and a group of age-matched neurologically
      normal controls on a driving simulation task. Measures of driving competence
      included the length of run, the number of infractions (omission of stop at
      pedestrian crossings, speed limits violation), the number of stops at traffic
      lights, the mean time to collision, and the number of off-road events. Results in
      the driving competence measures were correlated with scores obtained from simple
      visual reaction times and mini-mental state examination (MMSE). RESULTS: The
      patients with mild AD performed significantly worse than MCI subjects and
      controls on three simulated driving measures, length of run and mean time to
      collision (p < 0.001), and number of off-road events (p < 0.01). MCI subjects had
      only a significantly shorter time-to-collision than healthy controls (p < 0.001).
      Simple visual reaction times were significantly longer (p < 0.001) in patients
      with AD, compared to MCI and healthy controls, and showed a borderline
      significant relation (p = 0.05) with simulated driving scores. Driving
      performance in the three groups did not significantly correlate with MMSE score
      as measure of overall cognitive function. CONCLUSIONS: Mild AD significantly
      impaired simulated driving fitness, while MCI limitedly affected driving
      performance. Unsafe driving behaviour in AD patients was not predicted by MMSE
      scores.

PMID- 18615782
TI  - The enigma of yellow fever in East Africa.
AB  - Despite a safe and effective vaccine, there are approximately 200,000 cases,
      including 30,000 deaths, due to yellow fever virus (YFV) each year, of which 90%
      are in Africa. The natural history of YFV has been well described, especially in
      West Africa, but in East Africa yellow fever (YF) remains characterised by
      unpredictable focal periodicity and a precarious potential for large epidemics.
      Recent outbreaks of YF in Kenya (1992-1993) and Sudan (2003 and 2005) are
      important because each of these outbreaks have involved the re-emergence of a YFV
      genotype (East Africa) that remained undetected for nearly 40 years and was
      previously unconfirmed in a clinically apparent outbreak. In addition, unlike
      West Africa and South America, YF has yet to emerge in urban areas of East Africa
      and be vectored by Aedes (Stegomyia) aegypti. This is a significant public health
      concern in a region where the majority of the population remains unvaccinated.
      This review describes historical findings, highlights a number of disease
      indicators, and provides clarification regarding the natural history, recent
      emergence and future risk of YF in East Africa.

PMID- 18615784
TI  - Surface modification of polymer microfluidic devices using in-channel atom
      transfer radical polymerization.
AB  - In-channel atom transfer radical polymerization (ATRP) was used to graft a PEG
      layer on the surface of microchannels formed in poly(glycidyl methacrylate)-co
      (methyl methacrylate) (PGMAMMA) microfluidic devices. The patterned and cover
      plates were first anchored with ATRP initiator and then thermally bonded
      together, followed by pumping a solution containing monomer, catalyst, and ligand
      into the channel to perform ATRP. A PEG-functionalized layer was grafted on the
      microchannel wall, which resists protein adsorption. X-ray photoelectron
      spectroscopy (XPS) was used to investigate the initiator-bound surface, and EOF
      was measured to evaluate the PEG-grafted PGMAMMA microchannel. Fast, efficient,
      and reproducible separations of amino acids, peptides, and proteins were obtained
      using the resultant microdevices. Separation efficiencies were higher than
      1.0x10(4) plates for a 3.5 cm separation microchannel. Compared with microdevices
      modified using a previously reported ATRP technique, these in-channel modified
      microdevices demonstrated better long-term stability.

PMID- 18615785
TI  - Calculation of the isoelectric point of tryptic peptides in the pH 3.5-4.5 range
      based on adjacent amino acid effects.
AB  - Current algorithms for the calculation of peptide or protein pI, based on the
      charge associated with individual amino acids, can calculate pI values to within
      +/-0.2 pI units. Here, we present a new pI calculation algorithm that takes into
      account the effect of adjacent amino acids on the pI value. The algorithm
      accounts for the effect of adjacent amino acids+/-3 residues away from a charged
      aspartic or glutamic acid, as well as effects on the free C terminus, and applies
      a correction term to the corresponding pK values. The correction increments are
      derived from a 5000-peptide training set using a genetic optimization approach.
      The accuracy of the new pI values obtained with this method approaches the error
      associated with the manufacture of the IPG strip (<+/-0.03 pI units). The
      approach is demonstrated for cytosolic cell extracts derived from the breast
      cancer cell line DU4475, and from membrane preparations from human lung-tissue
      samples. One potential application of a more highly accurate pI calculation is
      data filtering of MS/MS outputs that will allow for more complex database
      searches including gene finding, and validation, and detection of coding single
      nucleotide polymorphisms in their expressed form.

PMID- 18615787
TI  - Protein separation using preparative-scale dynamic field gradient focusing.
AB  - Dynamic field gradient focusing uses an electric field gradient to separate and
      concentrate proteins in native buffers. A prototype preparative-scale dynamic
      field gradient focusing apparatus reproducibly separated hemoglobin and bovine
      serum albumin with a mean resolution of 2.64+/-0.503. Run-to-run variations in
      the hemoglobin's focal point and peak width appeared to be related to
      fluctuations in the shape of the electric field, rather than the 5% accuracy of
      the pump that provided the counter-flow in the separation annulus. The variation
      in the electric field gradient was probably due to the formation and expansion of
      an ion-depleted region at the top of the separation annulus.

PMID- 18615789
TI  - Floral attractants for the female soybean looper, Thysanoplusia orichalcea
      (Lepidoptera: Noctuidae).
AB  - BACKGROUND: The soybean looper, Thysanoplusia orichalcea (F.), is a polyphagous
      insect pest of vegetable crops. Indonesian in origin, it has spread to Europe,
      India, Africa, Australia and New Zealand. The identification of an attractant for
      female T. orichalcea could enable the development of alternative pest management
      strategies to those provided by insecticides or sex pheromones, which are often
      only attractive to males. RESULTS: Traps baited with synthetic lures derived from
      Canada thistle, Cirsium arvense (L.) Scop., floral volatiles attracted female T.
      orichalcea. Phenylacetaldehyde, a floral compound attractive to many Lepidoptera
      and present in C. arvense, was tested alone as an attractant for the soybean
      looper and caught significantly more female than male T. orichalcea. Trap catch
      was greatest when phenylacetaldehyde was combined with five prevalent volatiles
      present in C. arvense headspace collections: 2-phenylethyl alcohol, methyl
      salicylate, dimethyl salicylate, benzaldehyde and benzyl alcohol. Twice as many
      female moths as males were collected. CONCLUSION: Successful trapping of female
      T. orichalcea in either a lure-and-kill or a mass trapping system may offer an
      effective way to manage its population size.

PMID- 18615791
TI  - Preface: Tissue engineering and cell therapies: II.

PMID- 18615792
TI  - Population dynamics of human activated natural killer cells in culture.
AB  - The growth kinetics and population dynamics of recombinent interleukin-2 (rlL-2)
      stimulated human natural killer (NK) cell-enriched populations were studied in
      vitro. The NK-enriched populations was obtained from normal peripheral blood
      mononuclear cells (PBMNC) by immunomagnetic bead depletion of CD3(+) and CD5(+) T
      cells. The growth kinetics of NK cells, T cells, monocytes, and total cells are
      shown. In the absence of PBMNC accessory cells, the NK-enriched population showed
      limited expansion. In the presence of PBMNC accessory cells, the NK-enriched
      population expanded threefold more than in the absence of accessory cells due to
      increased NK cell growth rate and increased duration of exponential growth. Using
      a Transwell system, which separates two cell population by a polycarbonate
      membrane, the accessory cells were shown to act on the NK-enriched population via
      a diffusible factor. Accessory cell conditioned media was able to replace the
      accessory cell population to stimulate NK cell expansion. A monocyte-enriched
      population prepared by sheep red blood cell rosetting of T cells was extensively
      phenotyped and compared with the NK-enriched populations. Although the final
      cultured cells were phenotypically homogeneous for CD56(+)/CD3(-) NK cells, the
      initial NK precusor populations appear to be different. Namely, the NK cell
      precursors in the monocyte-enriched population were predominantly CD56(+)/CD2(-).
      Kinetic equations were formulated for this culture system and the effects of
      major culture variables are investigated.

PMID- 18615793
TI  - A 3-year experience of quality control and quality assurance in the multisite
      delivery of a lymphocyte-based cellular therapy for renal cell carcinoma.
AB  - Autolymphocyte therapy (ALT) is outpatient-based adoptive immunotherapy using ex
      vivo-activated memory T-cells. To support the safe and reproducible delivery of
      ALT at three cell processing facilities (Boston, MA; Atlanta, GA; Orange, CA) we
      created a comprehensive quality assurance/quality control program compliant with
      recent FDA guidance relevant to activated lymphocytes and somatic cell therapies.
      Each facility performed extensive QC testing to ensure sterility, viability, and
      proper cell yield. Additionally, several QC tests were performed at Cellocr's
      centralized reference laboratory to monitor cell potency and identity of the ex
      vivo-processed lymphocytes. We report here the successful implementation of this
      QA/QC program for ALT which has resulted in the safe preparation and delivery of
      cell infusion products amounting to over 3600 treatments at seven clinical sites
      nationwide. We believe this program will serve as a model for other cellular
      therapies.

PMID- 18615794
TI  - Preliminary validation of an activation assay for ex vivo activated T cells
      utilized in cancer immunotherapy.
AB  - An in vitro assay that measures the activation level of ex vivo activated (EVA) T
      cells currently being used in the adoptive immunotherapy of metastatic renal cell
      carcinoma has been developed. This assay is based on the ability of activated,
      but not resting. T cells to proliferate in response to the protein kinase C
      activator, phorbol myristate (PMA). To utilize this assay for in-process
      monitoring and control, we have begun an initial validation of the overall
      reproducibility of this assay. The proliferation of activated T cells in response
      to PMA, as measured by the mean cpm values of (3)H-thymidine incorporated, was
      demonstrated to have intra-assay coefficients of variation (cv's) for individual
      analysts that were typically less than 10% and rarely exceeded 20%. Activated T
      cells could be frozen and stored for at least 6 weeks with little or no
      deterioration in their ability to proliferate in response to PMA. Using these
      cells, inter-assay cv's that were typically less than 15% were obtained by
      individual analysts, and overall cv's of 10% to 25% were obtained for different
      samples assayed by different analysts at different times. This level of
      variability is very reasonable for a cellular assay. Further validation of this
      assay will address the issues of sensitivity, linearity and selectivity. To date,
      this assay has been used to analyze over 90 patient EVA cell samples and has
      revealed a broad range of proliferative responses to PMA. Taken together, these
      results suggest that this assay may be useful in defining the potency of the
      activated T cell used therapeutically.

PMID- 18615795
TI  - Serum-free media for cultures of primitive and mature hematopoietic cells.
AB  - The in vitro culture of human hematopoietic cells has many research and
      therapeutic applications. Traditionally, human hematopoietic cultures have been
      conducted using serum-containing media. The disadvantages inherent in the use of
      serum could be eliminated by the use of serum-free media. In this review, we
      summarize and discuss the current status of serum-free media for both mature and
      immature human hematopoietic cells. The mature hematopoietic cells discussed are
      of lymphoid (e.g., lymphokine activated killer cells and tumor infiltrating
      lymphocytes) and myeloid origin (e.g., monocytes/macrophages). The cultures of
      immature hematopoietic cells discussed are clonogenic and long-term cultures. In
      addition, we briefly review the types of human hematopoietic cells, their
      clinical applications, and the basic strategies and components used to formulate
      serum-free media, Finally, we outline future requirements and directions in the
      development of serum-free media for primitive hematopoietic cells.

PMID- 18615796
TI  - Microencapsulated human bone marrow cultures: a potential culture system for the
      clonal outgrowth of hematopoietic progenitor cells.
AB  - Currently the most successful methods for culturing human hematopoietic cells
      employ some form of perfused bioreactor system. However, these systems do not
      permit the clonal outgrowth of single progenitor cells. Therefore, we have
      investigated the use of alginate-poly-L-lysine microencapsulation of human bone
      marrow, combined with rapid medium exchange, as a system that may overcome this
      limitation for the purpose of studying the kinetics of progenitor cell growth. We
      report that a 12 to 24-fold multilineage expansion of adult human bone marrow
      cells was achieved in about 16 to 19 days with this system and that visually
      identifiable colonies within the capsules were responsible for the increase in
      cell number. The colonies that represented the majority of cell growth originated
      from cells that appeared to be present in a frequency of about 1 in 4000 in the
      encapsulated cell population. These colonies were predominantly granulocytic and
      contained greater than 40,000 cells each. Large erythroid colonies were also
      present in the capsules, and they often contained over 10,000 cells each. Time
      profiles of the erythroid progenitor cell density over time were obtained. Burst
      forming units erythroid (BFU-E) peaked around day 5, and the number of
      morphologically identifiable erythroid cells (erythroblasts through
      reticulocytes) peaked on day 12. We also report the existence of a critical
      inoculum density and how growth was improved with the use of conditioned medium
      derived from a microcapsule culture initiated above the critical inoculum
      density. Taken together, these results suggest that microencapsulation of human
      hematopoietic cells allows for outgrowth of progenitor, and possible
      preprogenitor, cells and could serve as a novel culture system for monitoring the
      growth and differentiation kinetics of these cells.

PMID- 18615797
TI  - The in vitro growth of a three-dimensional human dermal replacement using a
      single-pass perfusion system.
AB  - A human dermal replacement has been developed by seeding human neonatal dermal
      fibroblasts onto a biosorbable polyglactin (polyglycolide/polylactide) mesh and
      culturing in a bioreactor. The mesh provides the proper environment for the cells
      to attach, grow in a three-dimensional array, and establish a tissue matrix over
      a 2- to 3-week culture period. The dermal replacement has been characterized and
      found to contain a variety of naturally occurring dermal matrix proteins,
      including fibronectin, glycosaminoglycans, and collagen types I and III. To
      efficiently and reproducibly produce this dermal tissue equivalent, a closed,
      single-pass perfusion system was developed and compared with a static process. In
      the single-pas perfusion system, growth medium (containing ascorbic acid) was
      perfused around the 4 x 6 in. pieces of mesh at specific flow rates determined by
      nutrient consumption and waste production rates. The flow rates used for this
      system indicate that a diffusion-limited regime exists with a mean residence time
      greater than 1 h for essential nutrients and factors. By controlling glucose
      concentrations in the system to a delta of 0.70 g/L from the inlet to the outlet
      of the bioreactor, it took 6 fewer days to grow a tissue similar to that produced
      by the static system.

PMID- 18615798
TI  - Development of a bilayered living skin construct for clinical applications.
AB  - An in vitro construct of human skin (living skin equivalent, LSE) has been
      engineered using serially passaged human epidermal keratinocytes and human dermal
      fibroblasts with a matrix of type I collagen. Cells are obtained from neonatal
      foreskin. LSE is cast, cultured, and shipped in a single culture insert. The size
      and shape of the insert determines the size and shape of the LSE. The dermal
      matrix consists of dermal fibroblasts within a condensed collagen lattice. The
      overlying epidermis is developed at the air-liquid interface to generate a
      protective cornified layer. Serum was not necessary for development of the
      epidermis. LSE for graft (Graftskin) has handling characteristics similar to
      split-thickness skin allowing it to be meshed, stapled, and sutured. LSE was
      cryopreserved using 65% glycerol an rapid freezing. Viability and in vivo
      performance on athymic mice were similar to fresh LSE. Cells derived from human
      eccrine gland were able to invade and form tubules rudimentary appendages may be
      possible.

PMID- 18615799
TI  - Review: Whole skeletal muscle transplantation: mechanisms responsible for
      functional deficits.
AB  - One aspect of tissue engineering of skeletal muscle involves the transposition
      and transplantation of whole muscles to treat muscles damaged by injury or
      disease. The transposition of whole muscles has been used for many decades, but
      since 1970, the development of techniques for microneurovascular repair has
      allowed the transplantation of muscles invariably result in structural and
      functional deficits. The deficits are of the greatest magnitude during the first
      month, and then a gradual recovery results in the stabilization of structural and
      functional variables between 90 and 120 days. In stabilized vascularized grafts
      ranging from 1 to 3 g in rats to 90 g in dogs, the major deficits are
      approximately 25% decrease in muscle mass and in most grafts approximately 40%
      decrease in maximum force. The decrease in power is more complex because it
      depends on both the average shortening force and the velocity of shortening. As a
      consequence, the deficit in maximum power may be either greater or less than the
      deficit in maximum force. Tenotomy and repair are the major factors responsible
      for the deficits.Although the data are limited, skeletal muscle grafts appear to
      respond to training stimuli in a manner no different from that of control
      muscles. The training stimuli include traditional methods of endurance and
      strength training, as well as chronic electrical stimulation. Transposed and
      transplanted muscles develop sufficient force and power to function effectively
      to: maintain posture; move limbs; sustain the patency of sphincters; partially
      restore symmetry in the face; or serve as, or drive, assist devices in parallel
      or in series with the heart.

PMID- 18615800
TI  - Effects of substratum morphology on cell physiology.
AB  - Among the host of substratum properties that affect animal cell behavior, surface
      morphology has received relatively little attention. The earliest effect of
      surface morphology on animal cells was discovered almost a century ago when it
      was found that cells became oriented in response to the underlying topography.
      This phenomenon is now commonly known as contact guidance. From then until very
      recently, little progress has been made in understanding the role of surface
      morphology on cell behavior, primarily due to a lack of defined surfaces with
      uniform morphologies. This problem has been solved recently with the development
      of photolithographic techniques to prepare substrata with well defined and
      uniform surface morphologies. Availability of such surfaces has facilitated
      systematic in vitro experiments to study influence of surface morphology on
      diverse cell physiological aspects such as adhesion, growth, and function. For
      example, these studies have shown that surfaces with uniform multiples parallel
      grooves can enhance cell adhesion by confining cells in grooves and by
      mechanically interlocking them. Several independent studies have demonstrated
      that cell shape is a major determinant of cell growth and function. Because
      surface morphology has been shown to modulate the extent of cell spreading and
      cell shape, its effects on cell growth and function appear to be mediated via
      this biological coupling between cell shape and function. New evidence in the
      cell biology literature is emerging to suggest that surface morphology could
      affect other cell behavioral properties such as post-translational modifications.
      Further elucidation of such effects will enable better designs for implant and
      cell culture substrata.

PMID- 18615801
TI  - Multifunctional poly(ethylene glycol) semi-interpenetrating polymer networks as
      highly selective adhesive substrates for bioadhesive peptide grafting.
AB  - Novel artificial extracellular matrices were synthesized in the form of semi
      interpenetrating polymer networks containing copolymers of poly(ethylene glycol)
      and acrylic acid (PEG-co-AA) grafted with synthetic bioadhesive peptides onto
      exposed carboxylic acid moieties. These substrates were very resistant to cell
      adhesion, but when they were grafted with adhesive peptides they were highly
      biospecific in their ability to support cell adhesion. Extensive preadsorption of
      adhesive proteins or peptides did not render these materials cell adhesive; yet
      covalent grafting of adhesive peptides did render these materials highly cell
      adhesive even in the absence of serum proteins. Polymer networks containing
      immobilized PEG-co-AA were grafted with peptides at densities of 475 +/- 40
      pmol/cm(2). Polymer networks containing immobilized PEG-co-AA N-terminally
      grafted with GRGDS supported cell adhesion efficiencies of 42 +/- 4% 4 h after
      seeding and became confluent after 12 h. These cells displayed cell spreading and
      cytoskeletal grafted with inactive control peptides (GRDGS, GRGES, or no peptide)
      supported cell adhesion efficiencies of 0 +/- 0%, even when challenged with high
      seeding densities (to 100,000 cell/cm(2)) over 14 days. These polymer networks
      are suitable substrates to investigate in vitro cell-surface interactions in the
      presence of serum proteins without nonspecific protein adsorption adhesion
      signals other than those immobilized for study.

PMID- 18615802
TI  - Collagen fabrics as biomaterials.
AB  - Tissue-engineered implants require appropriate biomaterials to serve the required
      physical function of the tissue being repaired or replaced while facilitating
      remodeling of the implant. We report on the development of implantable fabrics
      manufactured from continuous collagen threads. The collagen threads are formed by
      extrusion of native, acid-extracted bovine collagen into a buffered solution of
      polyethylene glycol, followed by rinsing and air drying. The high manufacturing
      rate of such threads permits the production of collagen fabrics of various
      configurations. The fiber diameter can be controlled, and threads with dry
      diameters as low as 25 microm have been produced. Braids and bundles of collagen
      threads implanted as a replacement of the anterior cruciate ligament in a dog
      model were completely remodeled into host tissue by 12 weeks. Knitted collagen
      fabrics implanted in a rat abdominal repair model prevented herniation, and
      connective tissue ingrowth was observed within the fabric by 12 weeks.

PMID- 18615803
TI  - Spatial distribution of mammalian cells dictated by material surface chemistry.
AB  - Anisotropic cell culture surfaces patterned with amino and alkylsilanes can guide
      cell distribution and provide an approach to study important processes involved
      in tissue engineering, such as cell attachment and locomotion. By combining
      photolithographic and silane coupling techniques, glass coverslips were patterned
      with either n-octadecyldimethylchlorosilane (ODDMS) or dimethyldichlorosilane
      (DMS), and N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS). The
      alkylsilanes, theoretically, have similar methyl and methylene groups exposed at
      the surface but different structures, with DMS being amorphous and ODDMS ordered.
      Neuroblastoma cells, osteosarcoma cells, and fibroblasts plated on surfaces
      patterned with EDS/ODDMS and EDS/DMS specifically localized on the EDS regions,
      but distributed randomly on ODDMS/DMS patterned surfaces. The preferential
      assembly of cells onto EDS regions did not depend on the structure of the
      adjacent alkylsilane regions and was a time-dependent process. Angle dependent x
      ray photoelectron spectroscopy (XPS) and contact angle measurements indicated
      that EDS was immobilized on glass as a fractional hydrophilic monolayer, and
      ODDMS and DMS were bound as patchy amorphous hydrophobic multilayers. Neither
      surface coverage nor thickness of the overlayer seemed to be as important as
      surface chemistry, or charge, in guiding mammalian cell distribution. These
      results are consistent with the concept that mammalian cells attach to and are
      guided by positively charged surfaces.

PMID- 18615804
TI  - N-acetylglucosamine and adenosine derivatized surfaces for cell culture: 3T3
      fibroblast and chicken hepatocyte response.
AB  - 3T3 fibroblasts and primary chicken hepatocytes were cultured on derivatized
      polystyrene surfaces to examine the effect of cell-specific ligands on cellular
      morphology and growth. Surfaces were prepared by derivatizing chloromethylated
      polystyrene with N-acetylglucosamine (GlcNAc; recognized by the chicken
      asialoglycoprotein receptor) and adenosine (not recognized by adult hepatocytes).
      These surfaces were compared with tissue culture polystyrene (TCPS), acid-cleaned
      glass, and the unmodified chloromethylated polystyrene. The spreading,
      cytoskeletal structure and growth of the fibroblasts following attachment to
      these surfaces were examined. The extent of attachment, total protein levels, and
      DNA contents for surfaces-attached chicken hepatocytes were also measured.
      Fibroblast spreading was greatest on polymer surfaces derivatized with GlcNAc,
      whereas cytoskeletal structure and growth rate were independent of surface
      chemistry. Although chicken hepatocytes attached most efficiently to the GlcNAc
      derivatized polymer, the total protein and DNA levels of the surface-attached
      cells were not affected. In anticipation of the application of these polymers for
      cell culture and hybrid artificial organ design, the GlcNAc-derivatized
      polystryrene was fabricated into porous microcarriers. Fibroblasts grew avidly on
      the microcarriers, whereas chicken hepactocytes adhered well to the formed large
      aggregates around the microcarriers.

PMID- 18615805
TI  - Stereotypic culture systems for liver and bone marrow: evidence for the
      development of functional tissue in vitro and following implantation in vivo.
AB  - Stromal cell-associated liver cell and bone marrow (BM) culture on three
      dimensional nylon screen or polyglycolic acid (PGA) felt templates conveys
      certain functional advantages to the parenchyma of these tissues. Hepatic
      parenchymal cells (PC) manifest long-term ( approximately 2 month) expression of
      liver-specific activities including cytochrome P450 enzyme activity and the
      synthesis of albumin, fibrinogen, transferrin, and other proteins. PC also
      undergo proliferation in association with stromal cells that were pre-established
      on these templates. PC mitoses are directly proportional to available space
      within the template for their expansion indication that geometric or sterotypic
      parameters influence the growth of these cells in vitro. BM cultured on a similar
      template exhibits long-term multilineage hematopoietic expression and limited
      expansion of progenitor cell numbers. Progenitor cell concentration within the
      cultures can be substantially enhanced if these cells are liberated from co
      culture and reseeded onto a template containing fresh stromal cells. BM and liver
      cel cultures established on felt composed of bioresorbable PGA filaments was
      grafted into various sites in rats. Liver co-cultures generated sinusoids and
      other liver-like structures in situ; active hematopoietic blasts were observed at
      sites of BM co-culture grafts. Biodegradable polymer constructs may prove useful
      for certain clinical applications as vehicles for the delivery of tissues that
      were engineered in culture.

PMID- 18615806
TI  - Cerebral neurons, skeletal myoblasts, and cardiac muscle cells cultured on
      macroporous beads.
AB  - Biodegradable macroporous spherical microcarriers (MCs) offer a suitable
      substrate for adhesion, growth, and differentiation of cerebral neurons, skeletal
      myoblasts, and cardiac cells. The cavernous structure of these gelatin beads
      supplies a large surface and a tridimensional habitat for cell propagation.
      Within hours from their seeding, all three cell types became firmly attached to
      the MCs, forming cell-MC aggregates, which remained floating in the medium.
      Neuronal aggregates were composed mainly of single or groups of perikarya, and
      their sprouted nerve processes formed a ramified network. In skeletal muscle
      aggregates, fusion of myoblasts into myotubes occurred within 5 days. The
      myotubes, arranged in bundles having the same orientation, became striated and
      the whole aggregate, or parts of it, contracted spontaneously. Cardiac cells
      divided in the aggregate to form one or more layers of flat cells, which
      exhibited single microvilli. The cells were interconnected at uneven intervals
      and the whole aggregate contracted actively. Morphological and biochemical
      analysis of sampled aggregates ensured that cells reached the proper stage of
      maturation and could be used for either physiological and pharmacological studies
      or implantation into injured or dystrophic tissue.

PMID- 18615807
TI  - Hyphenation in sample preparation: advancement from the micro to the nano world.
AB  - Analysis at trace levels, an ideal area of application for hyphenated techniques,
      is steadily gaining importance. Many sample pre-concentration and clean-up
      methods have been hyphenated with core analytical techniques to accomplish the
      task of low level detection. The present article describes the state of the art
      of hyphenation of various techniques such as solid phase extraction, micro-solid
      phase extraction, dialysis, and chromatographic modalities etc. with liquid
      chromatography, gas chromatography, capillary electrophoresis, and spectroscopic
      methods. Besides, attempts have been made to address the hyphenation approach in
      microfluidic devices.

PMID- 18615808
TI  - Multi-residue methods for confirmatory determination of antibiotics in milk.
AB  - The prevalent use of antibiotics, e. g. sulphonamides, tetracyclines, beta
      lactams, macrolides, aminoglycosides, etc., in dairy farming to prevent and treat
      microbial infections e. g. mastitis, can be a potential source of veterinary drug
      residues in milk. Antibiotic residues constitute a risk to human health, since
      they can cause allergic reactions in hypersensitive individuals or they may lead
      to the appearance of drug-resistant bacteria. Analysis of these residues plays a
      key role in ensuring food safety. Regulatory agencies in the European Union and
      in other countries have established maximum residue limits and requirements
      concerning the performance of analytical methods and the interpretation of the
      results. This review describes the state of the art in the analytical strategies
      concerning the multi-class as well as the multi-residue analysis of antibiotics
      in milk. Since milk is a complex matrix due to its high protein and fat content,
      which often interfere in analytical procedures, special focus has been placed on
      sample preparation: extraction and clean-up. Confirmation of antibiotic residues
      according to European Decision 657/2002/EC has been also discussed.

PMID- 18615809
TI  - Traditional Chinese medicine and separation science.
AB  - Traditional Chinese medicines (TCMs) are getting more and more popular nowadays
      in the whole world for improving health condition of human beings as well as
      preventing and healing diseases. TCM is a multi-component system with components
      mostly unknown, and only a few compounds are responsible for the pharmaceutical
      and/or toxic effects. The large numbers of other components in the TCM make the
      screening and analysis of the bioactive components extremely difficult. So,
      separation and analysis of the desired chemical components in TCM are very
      important subjects for modernization research of TCM. Thus, many novel separation
      techniques with significant advantages over conventional methods were introduced
      and applied to separation and analysis of the chemical constituents in TCM. This
      review presents just a brief outline of the applications of different separation
      methods for the isolation and analysis of TCM constituents.

PMID- 18615813
TI  - Methacrylate-based short monolithic columns: enabling tools for rapid and
      efficient analyses of biomolecules and nanoparticles.
AB  - This review describes the novel chromatography stationary phase--a porous
      monolithic methacrylate-based polymer--in terms of the design of the columns and
      some of the features that make these columns attractive for the purification of
      large biomolecules. We first start with a brief summary of the characteristics of
      these large molecules (more precisely large proteins like immunoglobulins G and
      M, plasmid deoxyribonucleic acid (DNA), and viral particles), and a list of some
      of the problems that were encountered during the development of efficient
      purification processes. We then briefly describe the structure of the
      methacrylate-based monolith and emphasize the features which make them more than
      suitable for dealing with large entities. The highly efficient structure on a
      small scale can be transferred to a large scale without the need of making column
      modifications, and the various approaches of how this is accomplished are briefly
      presented in this paper. This is followed by presenting some of the examples from
      the bioprocess development schemes, where the implementation of the methacrylate
      based monolithic columns has resulted in a very efficient and productive process.
      Following this, we move back to the analytical scale and demonstrate the
      efficiency of the monolithic column--where the mass transfer between the
      stationary and mobile phase is greatly enhanced--for the in-process and final
      control of the new therapeutics. The combination of an efficient structure and
      the appropriate hardware results in separations of proteins with residence time
      less than 0.1 s.

PMID- 18615814
TI  - Porous polymer monoliths for extraction: diverse applications and platforms.
AB  - Polymer monoliths are becoming increasingly popular as sorbent materials, and,
      along with silica monoliths, they are sometimes touted as replacements for the
      particulate stationary phases used in HPLC. This critical and prospective review
      shows how polymer monoliths are in fact finding numerous extraction roles that do
      not resemble HPLC. They are showing great promise as extractors in a remarkable
      range of platforms, formats and hyphenated systems with functions ranging from
      chromatographic preconcentration to large-scale preparative extraction. Monolith
      surface chemistry, morphology and the approaches to monolith synthesis are
      discussed with regards to these emerging roles.

PMID- 18615815
TI  - Stationary phases for chromatography prepared by ring opening metathesis
      polymerization.
AB  - The chemistry of metathesis polymerization-derived stationary phases is
      summarized. Since both ring-opening metathesis and 1-alkyne polymerization
      triggered by well-defined transition metal alkylidenes are living polymerization
      methods, they allow for the controlled and highly reproducible synthesis of
      stationary phases in terms of both the nature and total content of the functional
      group(s) of interest. In addition, the high functionality tolerance of these
      polymerization techniques allows for creating chromatographic supports with an
      unprecedented diversity in terms of functional groups that may be introduced.
      Their applications in various areas of separation science such as SPE, ion
      chromatography, RP chromatography, chiral chromatography, and the high
      performance liquid chromatographic separation of biomolecules are summarized.
      Within the context of the latter topic, special attention will be given to
      metathesis polymerization-derived monolithic supports. Consideration will also be
      given to those aspects of polymer chemistry that are relevant to the separation
      performance of these supports.

PMID- 18615816
TI  - Use of polymer fiber stationary phases for liquid chromatography separations:
      Part I--Physical and chemical rationale.
AB  - The idea of using polymer fibers as stationary phases for LC is not a new one.
      There are in fact a number of good reasons for which they should be considered.
      To this point though, they have not produced sufficiently good performance to
      garner much commercial interest. Presented here are the physical and chemical
      rationale by which they should show enhanced performance relative to conventional
      stationary phases. Most notably, the mass transport and hydrodynamic
      characteristics suggest applications in areas of macromolecule and prep-scale
      separations. Additionally, there exists an incredible wealth of polymer surface
      chemistries and potential derivatization pathways that greatly exceed what is
      practical on conventional silica supports. The potential for important impact
      suggests further research into polymer fiber phases.

PMID- 18615817
TI  - Multidimensional liquid phase separations for mass spectrometry.
AB  - Large part of the current research in biology, medicine, and biotechnology
      depends on the analysis of DNA (genomics), proteins (proteomics), or metabolites
      (metabolomics). The advances in biotechnology also command development of
      adequate analytical instrumentation capable to analyze minute amounts of samples.
      The analysis of the content of single cells may serve as an example of ultimate
      analytical applications. Most of the separation techniques have been developed in
      the last three decades and alternative approaches are being investigated. At
      present, the main protocols for analyses of complex mixtures include 2-DE (IEF)
      followed by electrophoresis in SDS polyacrylamide gel (SDS-PAGE) and
      chromatographic techniques. Information-rich techniques such as MS and NMR are
      essential for the identification and structure analysis of the analyzed
      compounds. High resolution separation of the individual sample components is
      often a prerequisite for success. High resolution proteomic analysis in the
      majority of laboratories still relies on the time consuming and laborious offline
      methods. This review highlights some of the important aspects of 2-D separations
      including microfluidics.

PMID- 18615818
TI  - Considerations on HILIC and polar organic solvent-based separations: use of
      cyclodextrin and macrocyclic glycopetide stationary phases.
AB  - There is a natural tendency in science to prefer straightforward, logical
      classification systems. The use of mobile phase-stationary phase combinations
      that do not fit neatly into the standard "normal phase" or "reversed-phase"
      categories has been going on for over 50 years. The term "hydrophilic interaction
      chromatography" (HILIC) is sometimes being used as a general category for these
      "other" separations. In some cases, it may be appropriate and in others, not.
      Indeed the mechanistic constrains used to define the method seem to be varying
      with time. Given the name HILIC, it is assumed that water is not only present in
      the mobile phase, but also plays an essential role in the retention mechanism.
      However, there is residual water present in all organic solvents. Regardless, the
      number of reported separations in this alternative mode has increased
      tremendously in the last two decades. This is due to the advent of new stationary
      phases and an emphasis on polar, biologically important molecules. We discuss the
      relationships between HILIC and other chromatographic modes. We then examine two
      classes of stationary phases that have played a major role in these separations.
      These particular stationary phases can be used to provide appreciable mechanistic
      information as well.

PMID- 18615819
TI  - Optimizing protein extraction from plant tissues for enhanced proteomics
      analysis.
AB  - Plant tissues usually contain high levels of proteases and secondary metabolites
      that severely interfere with protein extraction, separation, and identification.
      Preparation of high-quality protein samples from plant tissues for proteomic
      analysis represents a great challenge. This article briefly describes the
      critical points in protein separation, especially secondary metabolites in plant
      tissues, and removal strategy. It provides an updated overview of three total
      protein extraction methods and their applications in proteomic analysis of
      various recalcitrant tissues.

PMID- 18615820
TI  - Human periosteum-derived cells from elderly patients as a source for cartilage
      tissue engineering?
AB  - The aim of this study was to establish the potential of human periosteum-derived
      cells from elderly patients as a cell source for cartilage tissue engineering by
      optimizing culture conditions for both proliferation and differentiation.
      Periosteum was obtained from the tibiae of nine patients. Biopsies were prepared
      for routine histological examination. Periosteum-derived cells were allowed to
      grow out from the remaining tissue, and were expanded in minimum essential medium
      containing D-valine (MEM-DV). Fetal bovine serum (FBS) or substitutes, fibroblast
      growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1) and non-essential
      amino acids were added to study proliferation. For differentiation of cells,
      serum-free medium was used supplemented with one or more isoforms of transforming
      growth factor-beta (TGFbeta) and/or IGF-1. Samples were analysed for expression
      of collagens type I, II and X by competitive RT-PCR, immunohistochemically, and
      histologically using Alcian blue staining. In all samples the cambium layer could
      hardly be detected. Periosteum-derived cells proliferated in serum-containing MEM
      DV. Optimal proliferation was found when this medium was supplemented with 100
      ng/ml FGF-2 and non-essential amino acids. Chondrogenesis was detected in 59% of
      micromasses that were cultured with TGFbeta isomers, and in 83% of the samples
      cultured in media to which two TGFbeta isoforms were added. Periosteum from
      elderly humans (mean age 66, range 41-76 years) has chondrogenic potential and
      remains an attractive cell source for cartilage tissue engineering. By expanding
      cells in MEM-DV, the selection of progenitor cells might be favoured, which would
      result in a higher cartilage yield for tissue engineering applications.

PMID- 18615821
TI  - Engineering microporosity in bacterial cellulose scaffolds.
AB  - The scaffold is an essential component in tissue engineering. A novel method to
      prepare three-dimensional (3D) nanofibril network scaffolds with controlled
      microporosity has been developed. By placing paraffin wax and starch particles of
      various sizes in a growing culture of Acetobacter xylinum, bacterial cellulose
      scaffolds of different morphologies and interconnectivity were prepared. Paraffin
      particles were incorporated throughout the scaffold, while starch particles were
      found only in the outermost area of the resulting scaffold. The porogens were
      successfully removed after culture with bacteria and no residues were detected
      with electron spectroscopy for chemical analysis (ESCA) or Fourier transform
      infra-red spectroscopy (FT-IR). Resulting scaffolds were seeded with smooth
      muscle cells (SMCs) and investigated using histology and organ bath techniques.
      SMC were selected as the cell type since the main purpose of the resulting
      scaffolds is for tissue engineered blood vessels. SMCs attached to and
      proliferated on and partly into the scaffolds.

PMID- 18615825
TI  - Application of the iodine-azide postcolumn reaction in RP-HPLC for the
      determination of thioguanine in urine.
AB  - The study focuses on the analysis of a sensitive, selective, and simple
      postcolumn detection method for thioguanine determination, based on the
      sensitizing induction of thioguanine on iodine-azide reaction and the combination
      technique of HPLC. The analysis was accomplished in the optimum conditions for
      iodine-azide detection system and HPLC separation. The values for the linear
      range, the LOD, and DOQ amounted to 0.8-1.7, 0.4, and 0.5 nmol/mL urine,
      respectively.

PMID- 18615826
TI  - Analysis of yohimbine alkaloid from Pausinystalia yohimbe by non-aqueous
      capillary electrophoresis and gas chromatography-mass spectrometry.
AB  - In the present work, the qualitative and quantitative analysis of Pausinystalia
      yohimbe-type alkaloids in the barks of Rubiaceae species is presented using
      different analytical approaches. Extracts of P. yohimbe were first examined by GC
      MS and the major alkaloids were identified. The quantitation of yohimbine was
      then accomplished by non-aqueous CE (NACE) with diode array detection. This
      approach was selected in order to use a running buffer fully compatible with
      samples in organic solvent. In particular, a mixture of methanol containing
      ammonium acetate (20 mM) and glacial acetic acid was used as a BGE. The same
      analytical sample was subjected to GC-MS and NACE analysis; the different
      selectivity displayed by these techniques allowed different separation profiles
      that can be useful in phytochemical characterization of the extracts. The linear
      calibration ranges were all 10-1000 microg/mL for yohimbine by GC-MS and NACE
      analysis. The recovery of yohimbine was 91.2-94.0% with RSD 1.4-4.3%. The LOD for
      yohimbine were 0.6 microg/mL by GC-MS and 1.0 microg/mL by NACE, respectively.
      The GC-MS and NACE methods were successfully validated and applied to the
      quantitation of yohimbine.

PMID- 18615827
TI  - Poisson's effects in electrical field flow fractionation.
AB  - Recent and earlier models of electrical field flow fractionation (ELFFF) have
      assumed that the electric field within the fluid domain is governed by Laplace's
      equation. This assumption results in a linear potential and a spatially constant
      field across the channel and is generally true for very dilute systems and
      relatively high effective potentials. Experimental studies show, however, that
      the effective potential within the channel may be less than 1% of the applied
      potential; this is apparently due to double layer formation and charge buildup at
      the poles. In such cases, local analyte concentrations can, nonetheless, be
      orders of magnitude higher than the bulk mean and the local potential small, both
      of which can lead to a nonlinear spatial distribution of the field strength. In
      such cases Poisson's equation must be used rather than Laplace's equation. Steady
      state ELFFF simulations were performed using a Poisson's equation-based model.
      The domain in which Laplace's equation is valid was identified and the effects of
      concentration and effective field strength on device performance were explored.

PMID- 18615828
TI  - Molecularly imprinted polymers for bisphenol A for HPLC and SPE from water and
      milk.
AB  - Molecularly imprinted polymers (MIPs) for bisphenol A (BPA) were prepared by two
      synthetic routes: semi-covalent and noncovalent methodology. The molecular
      imprinting effect was evaluated using the polymers in HPLC and SPE. Polymers
      prepared with noncovalent mode were proven more effective. These polymers were
      applied in SPE facilitating selective retention of BPA from bottled water and
      milk. The developed sample preparation was simple and efficient comprising only
      dilution of milk and MISPE prior to LC-MS analysis. Overall MISPE enhanced sample
      clean-up. Compared with control nonimprinted polymers and conventional C18 SPE
      cartridges, the MIPs exhibited selective analyte recognition. The method provided
      quantitative BPA recoveries, very good reproducibility (% RSDs lower than 7%),
      and low LOD (0.2 ng/g). MIP interacts similarly with deuterated BPA allowing its
      use as internal standard in LC-MS. The most critical parameters of MISPE were the
      organic content in loading-washing medium and the washing volume. Low flow rates
      in the elution step enhanced extraction recovery. Important advantages of the MIP
      were: the high breakthrough volumes (> 500 mL of water), high mass capacity (> 10
      ng/mg of MIP sorbent), good linearity, and good stability in performance for over
      35 cycles of use.

PMID- 18615829
TI  - Liquid-phase microextraction for rapid AP-MALDI and quantitation of nortriptyline
      in biological matrices.
AB  - A liquid-phase microextraction (LPME) method using a micropipette with disposable
      tips was demonstrated for coupling to atmospheric pressure MALDI-MS (AP-MALDI/MS)
      as a concentrating probe for rapid analysis and quantitative determination of
      nortriptyline drug from biological matrices including human urine and human
      plasma. This technique was named as micropipette extraction (MPE). The best
      optimized parameters of MPE coupled to AP-MALDI/MS experiments were extraction
      solvent, toluene; extraction time, 5 min; sample agitation rate, 480 rpm; sample
      pH, 7; salt concentration, 30%; hole size of micropipette tips, 0.61 mm (id); and
      matrix concentration, 1000 ppm using alpha-cyano-4-hydroxycinnamic acid (CHCA) as
      a matrix. Three detection modes of AP-MALDI/MS analysis including full scan,
      selective ion monitor (SIM), and selective reaction monitor (SRM) of MS/MS were
      also compared for the MPE performance. The results clearly demonstrated that the
      MS/MS method provides a wider linear range and lower LODs but poor RSDs than the
      full scan and SIM methods. The LOD values for the MPE under SIM and MS/MS modes
      in water, urine, and plasma were 6.26, 47.5, and 94.9 nM, respectively. The
      enrichment factors (EFs) of this current approach were 36.5-43.0 fold in water.
      In addition, compared to single drop microextraction (SDME) and LPME using a dual
      gauge microsyringe with a hollow fiber (LPME-HF) technique, the LODs acquired by
      the MPE method under MS/MS modes were comparable to those of LPME-HF and SDME but
      it is more convenient than both methods. The advantages of this novel method are
      simple, easy to use, low cost, and no contamination between experiments since
      disposable tips were used for the micropipettes. The MPE has the potential to be
      widely used in the future because it only requires a simple micropipette to
      perform all extraction processes. We believe that this technique can be a
      powerful tool for MALDI/MS analysis of biological samples and clinical
      applications.

PMID- 18615830
TI  - Dynamic liquid phase nanoextraction coupled to GC/MS for rapid analysis of
      methoxyacetophenone and anisaldehyde isomers in urine.
AB  - This study introduces a novel extraction technique in the nanoscale and
      challenges the limits of solvent extraction in the GC/MS using electronic
      ionization (EI) method for quantitative determination of six methoxyacetophenone
      (MAP) and anisaldehye (AAH) isomers in one drop of water and urine. This
      technique is termed as dynamic liquid phase nanoextraction (DLPNE). The optimum
      parameters for the DLPNE technique were: selection of solvent, toluene; sampling
      volume, 0.44 microL; dwell time, 2 s; number of sampling, 15; extraction time,
      1.5 min; volume of extraction solvent, 60 nL; and no salt addition. The LODs for
      this technique were 5-20 ng/mL. The RSDs were in the range of 9.7-12.6% (n = 6).
      The linear dynamic range of the calibration curve of DLPNE is from 0.02 to 0.5
      microg/mL with correlation coefficient (r(2)) >0.9705. The advantages of the
      DLPNE technique are rapidity, ease of operation, simple device, and extremely
      little solvent and sample consumption. This technique was also compared with the
      static liquid phase nanoextraction (SLPNE) while the SLPNE failed to detect any
      signal for the six isomers. We believe that this technique can be very useful for
      the detection of volatile organic compounds in environmental science from
      microscale of water or it can be applied to clinical or pharmaceutical
      application such as diagnosis of microamount of urine or blood samples by GC/MS.

PMID- 18615831
TI  - Efficient enrichment of alpha,beta-unsaturated bovine insulins-(C12)n using
      tweezing adsorptive bubble separation (TABS) with bovine serum albumin.
AB  - Alkyl-substituted insulin molecules are depository preparations used in the
      treatment of diabetes. The isolation and purification of these active compounds
      is performed on the hand of several complicated separation steps. In this work,
      nonmodified and new synthesized alpha,beta-unsaturated bovine insulins-(C12)(n)
      were selectively isolated from aqueous solution using tweezing adsorptive bubble
      separation (TABS) with BSA, which enabled reversible binding with the unpolar
      side chains of bovine insulin and its derivates. The bovine insulin/serum albumin
      complex could be efficiently transferred into the foam phase at pH 8 with an
      enrichment factor of 2.6 and a recovery of 89.7%. Experiments with alkylated
      alpha,beta-unsaturated bovine insulins-(C12)(n) performed at pH 9 enriched even
      quantitatively the complex under equal experimental conditions, accompanied with
      an enrichment factor of 3.3. Additionally performed radio immunoassay tests
      revealed that the immunological activity of alpha,beta-unsaturated bovine
      insulins-(C12)(n) remained unchanged after foaming.

PMID- 18615833
TI  - A cation-exchange material for protein separations based on grafting of thiol
      terminated sulfopropyl methacrylate telomers onto hydrophilized monodisperse
      divinylbenzene particles.
AB  - A strong cation-exchange separation material has been prepared from monodisperse
      divinylbenzene particles modified by a "grafting to" approach, utilizing as
      anchoring points epoxy groups introduced onto the surface of the particles via
      oxidation of residual vinyl groups. The grafted chains consisted of thiol
      terminated telomers of sulfopropyl methacrylate prepared by iniferter mediated
      polymerization, and grafting was performed by reaction of the corresponding
      thiolate anion with the surface epoxy groups. Attachment through epoxy moieties
      that were subsequently converted into 2,3-propanediol groups increased the
      hydrophilicity of the polymeric particles and incubation experiments showed no
      signs of the proteins denaturing on the column during an extended contact time of
      1 h at room temperature. The performance of the grafted material was demonstrated
      by the chromatographic separation of cytochrome C, lysozyme, myoglobin, and
      ribonuclease A, in a cation-exchange mode.

PMID- 18615834
TI  - Analysis of native carotenoid composition in orange juice using C30 columns in
      tandem.
AB  - In the present contribution, a novel analytical approach based on using serial
      coupled conventional LC columns is proposed to the study of the native carotenoid
      composition of orange juice. The great difficulties that are found when analyzing
      complex carotenoid samples, due to the high natural variability of these
      compounds as well as to the presence of carotenoid esters are well documented. To
      overcome some of these limitations, we have developed a methodology including the
      study of both the saponified and the intact sample by means of two different LC
      DAD/APCI-MS methods. The increase in the resolution and separation power obtained
      when using two serial coupled C(30) columns is demonstrated, and significant
      increases in peak capacity have been achieved. By using this new methodology, 44
      different carotenoids have been tentatively identified. Among them, several
      violaxanthin diesters have been directly identified in orange juice for the first
      time. The main carotenoids in orange juice were violaxanthin, lutein,
      luteoxanthin, 9-cis-antheraxanthin, and beta-cryptoxanthin. Some of them were
      found in both their free and esterified forms. To the best of our knowledge, this
      is the first application of serial couplings of C(30) columns for the
      identification of the native carotenoid composition of natural matrices.

PMID- 18615835
TI  - The impact of using different costing methods on the results of an economic
      evaluation of cardiac care: microcosting vs gross-costing approaches.
AB  - BACKGROUND: Published guidelines on the conduct of economic evaluations provide
      little guidance regarding the use and potential bias of the different costing
      methods. OBJECTIVES: Using microcosting and two gross-costing methods, we (1)
      compared the cost estimates within and across subjects, and (2) determined the
      impact on the results of an economic evaluation. METHODS: Microcosting estimates
      were obtained from the local health region and gross-costing estimates were
      obtained from two government bodies (one provincial and one national). Total
      inpatient costs were described for each method. Using an economic evaluation of
      sirolimus-eluting stents, we compared the incremental cost-utility ratios that
      resulted from applying each method. RESULTS: Microcosting, Case-Mix-Grouper (CMG)
      gross-costing, and Refined-Diagnosis-Related grouper (rDRG) gross-costing
      resulted in 4-year mean cost estimates of $16,684, $16,232, and $10,474,
      respectively. Using Monte Carlo simulation, the cost per QALY gained was $41,764
      (95% CI: $41,182-$42 346), $42,538 (95% CI: $42 167-$42 907), and $36,566 (95%
      CI: $36,172-$36,960) for microcosting, rDRG-derived and CMG-derived estimates,
      respectively (P<0.001). CONCLUSIONS: Within subject, the three costing methods
      produced markedly different cost estimates. The difference in cost-utility values
      produced by each method is modest but of a magnitude that could influence a
      decision to fund a new intervention.

PMID- 18615836
TI  - Genetic information, obesity, and labor market outcomes.
AB  - Economists have argued that obesity may lead to worse labor market outcomes,
      especially for women. Empirical methods to test this hypothesis have not thus far
      adequately controlled for the endogeneity of obesity. We use variation in
      genotype to predict variation in phenotype (obesity). Genetic information from
      specific genes linked to obesity in the biomedical literature provides strong
      exogenous variation in the body mass index and thus can be used as instrumental
      variables. These genes predict swings in weight of between 5 and 20 pounds for
      persons between five and six feet tall. We use additional genetic information to
      control for omitted variables correlated with both obesity and labor market
      outcomes. We analyzed data from the third wave of the Add Health data set, when
      respondents are in their mid-twenties. Results from our preferred models show no
      effect of lagged obesity on the probability of employment or on wages, for either
      men or women. This paper shows the potential of using genetic information in
      social sciences.

PMID- 18615837
TI  - Formation of b(1)-1 and the corresponding a(1)-1 product ions in the mass spectra
      of N-{para-(ferrocenyl)benzoyl} dipeptide esters.

PMID- 18615838
TI  - Fractionation of free and conjugated steroids for the detection of boldenone
      metabolites in calf urine with ultra-performance liquid chromatography/tandem
      mass spectrometry.
AB  - For over a decade there has been an intensive debate on the possible natural
      origin of boldenone (androst-1,4-diene-17beta-ol-3-one, 17beta-boldenone) in calf
      urine and several alternative markers to discriminate between endogenously formed
      boldenone and exogenously administered boldenone have been suggested. The
      currently approved method for proving illegal administration of beta
      boldenone(ester) is the detection of beta-boldenone conjugates. In the presented
      method the sulphate, glucuronide and free fractions are separated from each other
      during cleanup on a SAX column to be able to determine the conjugated status of
      the boldenone metabolites. The sulphate and glucuronide fractions are submitted
      to hydrolysis and all three fractions are further cleaned up on a combination of
      C18/NH2 solid-phase extraction (SPE) columns. Chromatographic separation of the
      boldenone metabolites was achieved with a Waters Acquity UPLC instrument using a
      Sapphire C18 (1.7 microm; 2x50 mm) column within 5 min. Detection of the analytes
      was achieved by electrospray ionisation tandem mass spectrometry. The decision
      limits of this method, validated according to Commission Decision 2002/657/EC,
      were 0.08 ng mL(-1) for androsta-1,4-diene-3,17-dione, 0.13 ng mL(-1) for androst
      4-ene-3,17-dione, 0.11 ng mL(-1) for 17alpha-boldenone, 0.07 ng mL(-1) for 17beta
      boldenone, 0.24 ng mL(-1) for 5beta-androst-1-en-17beta-ol-3-one and 0.58 ng mL(
      1) for 6beta-hydroxy-17beta-boldenone. Because of the fractionation approach used
      in this method there is no need for conjugated reference standards which often
      are not available. The disadvantage of needing three analytical runs to determine
      the conjugated status of each of the metabolites was overcome by using fast
      chromatography.

PMID- 18615839
TI  - The administration of an adenoviral thymidine kinase suicide gene to the uterine
      artery of rabbits does not affect fertility: a safety study of pregnant and
      nonpregnant rabbits and their offspring.
AB  - BACKGROUND: Adenoviral gene therapy, based on herpes simplex virus thymidine
      kinase (AdvTK) is being developed for clinical use but no safety data are
      available with respect to the effects on female germ cells should the virus
      accidentally be released into systemic circulation. We studied the effects of
      AdvTK gene therapy on ovaries and germ cells in pregnant and nonpregnant rabbits
      and also the potential transmission of a transgene to offspring. METHODS: To
      mimic the severest of conditions, gene transfer was made by direct catheter
      mediated injection into the uterine artery of pregnant and nonpregnant rabbits.
      AdvTK or AdvLacZ at 1 x 10(10) pfu were used for gene transfer. Ganciclovir was
      administered to AdvTK-treated rabbits to induce gene therapy. The rabbits were
      mated 6 and 12 weeks following gene transfer and the surviving young (89 from a
      total of 114) were analysed. RESULTS: No change in fertility was observed in the
      two matings after the gene transfer. In addition, no change was observed in
      ovarian histology between the AdvTK group, the AdvLacZ group and the nontreated
      controls. Southern blotting analysis showed no genomic integration of the
      transgene. However, in PCR analysis, transgene DNA was found in 9.3% of the
      litter samples. This was not the case for results from the reverse transcription
      PCR assay. CONCLUSIONS: Although AdvTK gene therapy may initially affect ovarian
      cells, the influence appears to be transient. However, after direct exposure of
      the ovarian cells in high concentration of adenoviruses, transmission of a
      transgene in the offspring cannot be excluded.

PMID- 18615840
TI  - The absorption, distribution, metabolism and elimination of bevirimat in rats.
AB  - Bevirimat is the first drug in the class of maturation inhibitors, which treat
      HIV infection by disrupting the activity of HIV protease enzyme with a mechanism
      of action distinct from that of conventional protease inhibitors. The absorption,
      distribution, metabolism and elimination characteristics of single intravenous
      (25 mg/kg) and oral (25 mg/kg and 600 mg/kg) doses of 14C-bevirimat were studied
      in male Sprague Dawley and Long Evans rats. Pharmacokinetic and mass-balance
      studies revealed that bevirimat was cleared rapidly (within 12-24 h) after
      dosing, although plasma radioactivity was quantifiable up to 168 h. Radioactive
      metabolites of bevirimat were responsible for approximately 60-80% of plasma
      radioactivity. Systemically available bevirimat was predominantly (97%) excreted
      via bile in the faeces, with <or=1% of the dose excreted renally. Less than 0.1%
      of the dose was excreted in expired air. Quantitative whole-body autoradiography
      detected high quantities of radioactivity in the bile and liver soon after
      intravenous dose administration, and evidence of biliary excretion present during
      the 8 h following oral dosing. Oral bioavailability for the 25 mg/kg dose of
      bevirimat was estimated at 22-24% by pharmacokinetic and mass-balance methods,
      with bioavailability decreasing disproportionately with increasing dose for the
      600 mg/kg group.

PMID- 18615841
TI  - Carcinogenic chromium(VI)-induced protein oxidation and lipid peroxidation:
      implications in DNA-protein crosslinking.
AB  - Hexavalent chromium [Cr(VI)] compounds are Group-I human carcinogens. Cr(VI)
      induced DNA-protein crosslinks (DPCs) have been implicated in the mutagenic and
      carcinogenic effects of Cr(VI). Although multiple mechanisms have been suggested
      for Cr(VI)-induced DNA-protein crosslinking, the mechanism of formation of DNA
      protein crosslinks is not well understood. In this study, we explored the
      hypothesis that Cr(VI)-induced DPCs could be formed via generation of protein
      carbonyls and malonaldehyde (MDA) through protein oxidation and lipid
      peroxidation, respectively. Treatment of human leukemic T-lymphocyte MOLT4 cells
      with potassium chromate induced the formation of protein carbonyls and DPCs
      within 2 h, but increased the level of MDA only after 4 h, in a dose-dependent
      manner. Chromate treatment of MOLT4 cell homogenates also resulted in increased
      formation of MDA and protein carbonyls in a dose-dependent manner. EPR
      spectrometry in combination with spin trapping techniques revealed that reaction
      of Cr(VI) with biological reductants such as NADPH, glutathione reductase or
      H(2)O(2) generates Cr(V) and (*)OH radicals. Pretreatment of cells with
      antioxidants such as alpha-tocopherol or Tiron inhibited chromate-induced
      increase in formation of protein carbonyls, MDA and DPCs, but pretreatment of
      cells with riboflavin or 3-aminotriazole, a catalase inhibitor, had the opposite
      effect. Our results, for the first time, demonstrate that Cr(VI) exposure
      increases the cellular level of protein carbonyls and that Cr(VI)-induced DPCs
      may be formed, at least in part, via generation of protein carbonyls.

PMID- 18615842
TI  - Comparison of two extraction procedures for determination of drugs of abuse in
      human saliva by high-performance liquid chromatography.
AB  - High performance liquid chromatography in combination with diode array detection
      (HPLC-DAD) was used to determine morphine, 6-acetylmorphine, cocaine,
      benzoylecgonine, cocaethylene, methadone and 2-ethylene-1,5-dimethyl-3,3,
      diphenylpyrrolidine in human saliva. For comparison, samples were prepared by
      either liquid-liquid extraction in Toxitubes A or microwave-assisted extraction
      (MAE), by mixing 1 ml of saliva with 10 ml of chloroform and operating at 100
      degrees C for 10 min. Acetonitrile and 0.02 m phosphate buffer at pH 6.5 were
      used as mobile phase in HPLC in gradient mode. The detector response was linear
      over the drug concentration range of 0.05-2.0 microg ml(-1) in human saliva. The
      analytical method was validated by determining its precision and accuracy (n =
      5), which were lower than 5% as relative standard deviation and 6% as relative
      error. Limits of detection ranged from 10 to 35 ng ml(-1); mean recoveries of
      drugs were from 53 to 95% with Toxitubes A and from 83 to 100% with MAE at two
      different concentrations (0.1 and 1.0 microg ml(-1)). The proposed method was
      applied to 24 saliva samples from individuals poisoned with opiates and/or
      cocaine.

PMID- 18615843
TI  - Personal standards, self-evaluation and perceived benefits of thinness in girls
      and young women with disturbed eating.
AB  - The aim of this study was to examine personal standards, self-evaluation and
      perceived benefits of thinness in Swedish females 14-21 years with disturbed
      eating (DE) and to compare these to a group with other psychosocial problems and
      to a symptom free group. Seventy subjects with DE-group, 65 subjects with
      psychosocial problems and 70 symptom free subjects were compared regarding items
      selected from four questionnaires. High personal standards expressed in a
      competitive way were specific for the DE-group. In comparison with the other
      groups the DE-group also reported significantly more perceived benefits of
      thinness and they more frequently believed that thinness would make them more
      popular. The DE-group also reported a more negative self-evaluation, although
      this was a trait shared with the subjects with other psychosocial problems and
      consequently not specific for the DE-group. Identifying specific factors that
      perpetuate DE habits is important in order to improve our understanding and
      enhance the treatment of eating disorders.

PMID- 18615844
TI  - Modality of physical exercise and cognitive function in Hong Kong older Chinese
      community.
AB  - OBJECTIVE: We reported the association between modality of Physical Exercise and
      cognitive function in 782 older Chinese adults assessed in the second phase of a
      population survey for dementia in Hong Kong. METHODS: Profiles of physical
      exercise was measured by a questionnaire (no exercise, stretching, aerobic and
      mind-body exercise). Cognitive Assessments included the CMMSE, ADAS-Cog, and
      Category Verbal Fluency Test (CVFT). RESULTS: The aerobic and mind body exercise
      groups with longer exercise habits (>5 years) had higher scores in most cognitive
      tests (Kruskal Wallis tests, p < 0.01). Beneficial effects were more significant
      in the young old group from 65- 75 years. CONCLUSIONS: Possible age related
      specific effects of aerobic and mind body exercise on cognitive reserve are
      worthy of further exploration.

PMID- 18615847
TI  - Specialization and competition in dental health services.
AB  - The number of specialists within dental health services has increased over the
      last few years. This raises the issue of how the services should be organized and
      funded. We describe the effect of one way of organizing the services, which is by
      relying on competition. In Norway, some oral specialists face real competition
      with general dental practitioners for the same patients (prosthetists,
      periodontists and endodontists), while other specialists do not (orthodontists
      and oral surgeons). The latter specialists have skills that give them exclusive
      possibilities to practice their profession. We find that competition can be
      effective for the specialists who experience real competition with general dental
      practitioners for patients. In situations where real competition does not exist,
      specialists can obtain market power and raise their fees. Our results are based
      on an analysis of a representative set of data from general dental practitioners
      and specialists in Norway. The specialities in which practitioners can exercise
      market power raise challenges related to the type of public policy that can
      reduce this market power in an appropriate way, and without involving too large
      costs for the authorities.

PMID- 18615848
TI  - Role of heterochromatin in suppressing subtelomeric recombination in fission
      yeast.
AB  - Telomere length is regulated by a complex interplay of several factors, including
      telomerase, telomere-binding proteins, DNA replication machinery and
      recombination. In yeast, DNA polymerase alpha is required for de novo synthesis
      of telomeres from broken ends of DNA, and it also suppresses the elongation of
      normal telomeric repeats. Heterochromatin proteins Clr1-Clr4 and Swi6 and DNA
      polalpha organize heterochromatin structure at mating type, centromere, rDNA and
      telomere regions that are refractory to transcription and recombination in
      Schizosaccharomyces pombe. Here, we have addressed the role of heterochromatin
      structure in regulating the integrity and organization of telomeric regions.
      Here, we show that subtelomeric duplication and rearrangements occur in polalpha
      and heterochromatin mutants and find that some of the putative duplication events
      are dependent on the Rad50 pathway. Thus, our study shows a role of
      heterochromatin in maintaining the integrity of the subtelomeric regions by
      suppressing their recombination in Sz. pombe.

PMID- 18615849
TI  - Impact of APOE status on cognitive maintenance in healthy elderly persons.
AB  - OBJECTIVE: The epsilon4 allele, a variant of the apolipoprotein E (ApoE) gene, is
      the most prominent genetic risk factor for sporadic, non-familial Alzheimer's
      disease (AD) currently known. We investigated the impact of the ApoE-epsilon4
      status on cognitive performance at repeated test administration in elderly non
      symptomatic persons, with a specific focus on practice effects. METHODS: Three
      hundred and fifty-five physically and mentally healthy participants of the Basel
      Study on the Elderly (119 F, 236 M; age 68.3 +/- 7.6; years of education 12.7 +/-
      3.1; Mini-Mental State scores 29.0 +/- 1.0) were grouped into ApoE epsilon4
      carriers and ApoE epsilon4 non-carriers (36.9% and 63.1% of the sample,
      respectively). Participants were assessed at the beginning of the longitudinal
      study and on average two years later by means of the California Verbal Learning
      Test (CVLT) and the Consortium to Establish a Registry for Alzheimer's Disease
      Neuropsychological Assessment Battery (CERAD-NAB), a multidimensional cognitive
      test battery. Baseline and change scores were analyzed with multiple regression
      procedures and adjusted for age, education and gender; change scores were also
      adjusted for baseline performance. RESULTS: The ApoE epsilon4 non-carriers showed
      slightly better performance with regard to most cognitive parameters at baseline.
      Mean practice effects of the ApoE epsilon4 non-carriers in 12 out of 13 CVLT
      variables and in five out of the nine main CERAD-NAB variables were above the
      50th percentile, while those of the ApoE epsilon4 carriers were below the 50th
      percentile in the respective distributions of test-retest change scores.
      CONCLUSIONS: The epsilon4 allele of the ApoE gene has a negative impact on
      cognitive performance, notably on episodic memory functions, in physically and
      mentally healthy aged persons. Practice effects seen in carriers of the ApoE
      epsilon4 were inferior in most areas tested to the effects seen in ApoE epsilon4
      non-carriers. Further follow-up of these subjects will help to determine the
      clinical significance of these findings.

PMID- 18615850
TI  - Globular adiponectin stimulates glucose transport in type 2 diabetic muscle.
AB  - BACKGROUND: Adiponectin acts as an insulin sensitizer in rodent models. The
      direct effect of adiponectin in intact type 2 diabetic muscle is unknown. We
      examined whether adiponectin stimulates glucose transport in isolated skeletal
      muscle strips from type 2 diabetic men. METHODS: We obtained open muscle biopsies
      from 12 men with type 2 diabetes (56 +/- 1 years, 30.5 +/- 1.1 kg/m(2)), and from
      15 non-diabetic men (59 +/- 1 years, 28.0 +/- 1.0 kg/m(2)). Skeletal muscle
      strips were isolated and exposed to globular adiponectin (2.5 microg/mL), insulin
      (120 nM) and/or AICAR (1 mM) in vitro for 1 h. Glucose transport was analysed by
      accumulation of intracellular 3-O-methyl [(3)H] glucose, phosphorylation of Akt
      Ser(473) and Akt-Thr(308) was determined using phosphospecific antibodies, and
      adiponectin receptor 1 and 2 content was measured using specific antibodies.
      RESULTS: Globular adiponectin increased glucose transport rate by 1.3-fold (P <
      0.01) in type 2 diabetic, but not in non-diabetic muscle. Insulin-stimulated
      glucose transport rate was unaltered by exposure to globular adiponectin in
      either group. AICAR increased glucose transport and enhanced insulin-stimulated
      glucose transport in type 2 diabetic and non-diabetic muscles. Insulin-stimulated
      phosphorylation of Akt-Ser(473) or Akt-Thr(308) was comparable in type 2 diabetic
      and non-diabetic muscles, and unaltered by the addition of globular adiponectin
      in either group. Adiponectin receptor expression was similar in skeletal muscle
      from type 2 diabetic and non-diabetic men. CONCLUSIONS: Globular adiponectin
      directly increases glucose transport in skeletal muscle from type 2 diabetic
      patients. This may occur via Akt-independent signalling routes.

PMID- 18615851
TI  - Effects of androgens on insulin action in women: is androgen excess a component
      of female metabolic syndrome?
AB  - Hyperinsulinemia as a consequence of insulin resistance causes hyperandrogenemia
      in women. The objective was to review evidence for the converse situation, i.e.
      whether androgens adversely influence insulin action. Androgen excess could
      potentially contribute to the pathogenesis of insulin resistance in women with
      polycystic ovary syndrome (PCOS), metabolic syndrome/type 2 diabetes, and in
      obese peripubertal girls. An Entrez-PubMed search was conducted to identify
      studies addressing the relationship of androgens with metabolic syndrome/type 2
      diabetes in women. Studies reporting outcomes of androgen administration,
      interventions to reduce androgen effects in hyperandrogenemic women, and basic
      studies investigating androgen effects on insulin target tissues were reviewed.
      Multiple studies showed associations between serum testosterone and insulin
      resistance or metabolic syndrome/type 2 diabetes risk in women, but their cross
      sectional nature did not allow conclusions about causality. Androgen
      administration to healthy women was associated with development of insulin
      resistance. Intervention studies in women with hyperandrogenism were limited by
      small subject numbers and use of indirect methods for assessing insulin
      sensitivity. However, in three of the seven studies using euglycemic
      hyperinsulinemic clamps, reduction of androgen levels or blockade of androgen
      action improved insulin sensitivity. Testosterone administration to female rats
      caused skeletal muscle insulin resistance. Testosterone induced insulin
      resistance in adipocytes of women in vitro. In conclusion, the metabolic
      consequences of androgen excess in women have been under-researched. Studies of
      long-term interventions that lower androgen levels or block androgen effects in
      young women with hyperandrogenism are needed to determine whether these might
      protect against metabolic syndrome/type 2 diabetes in later life.

PMID- 18615852
TI  - Saturation transfer double-difference NMR spectroscopy using a dual solenoid
      microcoil difference probe.
AB  - An experiment designed to collect a saturation transfer double difference (STDD)
      NMR spectrum using a solenoid microcoil NMR difference probe is reported. STDD
      NMR allows the investigation of ligand-biomolecule binding, with moderate
      concentration requirements for unlabeled molecular targets and the ability to
      discern binding events in the presence of non-binding ligands. The NMR difference
      probe acquires the signals from two different samples at once, and cancels common
      signals automatically through a mechanism of switching between parallel
      excitation and serial acquisition of the sample signals. STDD spectra were
      acquired on a system consisting of human serum albumin and two ligands, octanoic
      acid and glucose. The non-binding ligand, glucose, was cancelled internally
      through phase cycling, while the protein signal was subtracted automatically by
      the difference probe. The proton NMR resonance signal from octanoic acid remained
      in the double difference spectrum. This work demonstrates that the double
      difference can be performed both internally and automatically through the
      utilization of the solenoid microcoil NMR difference probe and STDD-NMR pulse
      sequence, resulting in a clean signal from the binding ligand with good protein
      background subtraction and an overall favorable result when compared to the
      conventional approach.

PMID- 18615853
TI  - Genetic variants in protein kinase C zeta gene and type 2 diabetes risk: a case
      control study of a Chinese Han population.
AB  - BACKGROUND: Previous investigations of the protein kinase C zeta (PRKCZ) gene, a
      susceptibility factor for type 2 diabetes mellitus (T2DM), have focussed on its
      single nucleotide polymorphisms (SNPs). In a departure from these earlier
      studies, we tested six tagging markers of PRKCZ based on the Hapmap database to
      evaluate their association with T2DM. METHODS: PCR-RFLP was performed to test the
      genotypes in type 2 diabetes patients (n = 343) and normal controls (n = 429).
      Insulin-related indexes were calculated from levels of fasting plasma insulin
      (FPI) and fasting plasma glucose (FPG). RESULTS: The variant genotypes,
      rs3753242TT, rs2503706CT, rs2503706CT/ TT and rs262654TT were associated with
      T2DM. And the significance remained for rs3753242 TT (p < 0.001) after the false
      discovery rate (FDR) correction. There was a doubling in the prevalence of the
      TTGCCC haplotype in the case subjects (14.2%) compared with the control subjects
      (6.9%) [OR (95% CI) = 2.19(1.49-3.22)]. In the control group, none of the
      haplotypes studied was associated with insulin-related indexes. CONCLUSIONS: The
      PRKCZ gene variants associated with the development of T2DM in this study must be
      investigated in a larger population to reveal any potential effects on
      metabolism.

PMID- 18615854
TI  - The valuation of prenatal life in economic evaluations of perinatal
      interventions.
AB  - Perinatal interventions delivered during the prenatal period have the potential
      to directly impact prenatal life. The decision on when to begin 'counting' the
      life of an infant in the calculus has received little attention in previous
      economic evaluations of perinatal interventions. We illustrate, using data from a
      recent trial-based economic evaluation of magnesium sulphate given to women with
      pre-eclampsia to prevent eclampsia, how different definitions of when human life
      commences can have a significant impact upon cost-effectiveness estimates based
      on composite outcome measures such as life years or quality-adjusted life years
      gained or disability-adjusted life years averted. Further, we suggest ways in
      which methods in this area can be improved.

PMID- 18615855
TI  - Understanding care of people with dementia in Spain: cohabitation arrangements,
      rotation and rejection to long term care institution.
AB  - BACKGROUND: Most people with dementia in Spain live at home with their families.
      Current changes in the family structure are transforming the care of people with
      dementia through new cohabitation arrangenments and rotation practices.
      OBJECTIVE: To describe the cohabitation arrangements of families of people with
      dementia in Spain and to understand the caregivers' characteristics related to
      rotation and the rejection of long term care institutions. METHODS: A cross
      sectional study -NEDICES study- was conducted using both quantitative and
      qualitative methodologies.150 caregivers of people with dementia from two
      communities from Madrid, Spain, were surveyed using a questionnaire designed to
      describe cohabitation arrangements and care. Qualitative methods included: 13
      caregivers participating in focus groups, and 3 caregivers in Semi Structured
      Interviews aimed to understand rotation practices and rejection to long term care
      institution. RESULTS: Characteristics related with rotation were: sex of persons
      with dementia, widowhood, socio-economic status, caregiver relationship and
      burden of the caregiver. The qualitative study showed that the use of the
      rotation was related to normative behaviors and with obligation feelings, along
      with a change in the role of women in the current Spanish family. The use of long
      term care institutions was related to geographical distance of the family.
      CONCLUSIONS: The results of this study suggest that rotation has appeared in
      Spain as a new mechanism of care for people with dementia, and its related to the
      rejection of long term care institutions.

PMID- 18615856
TI  - 1H and 13C NMR assignments for new heterocyclic TAM leuco dyes, (2Z,2'E)-2,2'-(2
      phenyl propane-1,3-diylidene) bis(1,3,3-trimethylindoline) derivatives. Part II.
AB  - The (1)H and (13)C NMR spectra of the novel heterocyclic Leuco-TAM dyes, (2Z,
      2'E)-2,2'-(2-phenyl propane-1,3-diylidene) bis(1,3,3-trimethylindoline)
      derivatives 1-4 as precursors of triarylmethane (TAM)(+) (Malachite Green FB
      analog) dyes were completely assigned by 1D and 2D NMR experiments, including
      DEPT, COSY, HSQC, HMBC, and NOESY. Especially, the diastereotopic gem-dimethyl
      protons at the C3 and C3' positions of the FB rings were definitively assigned.
      The (Z,E) isomers adopt the energetically favored three-bladed propeller
      conformation in solution.

PMID- 18615858
TI  - Sequence requirements for Nalpha-terminal acetylation of yeast proteins by NatA.
AB  - NatA is the major N-terminal acetyltransferase of the yeast Saccharomyces
      cerevisiae. In this study, we took advantage of our recent data on N-terminal
      acetylation of proteins of the yeast protein map to update the list of proteins
      with known NatA-dependent acetylation status. Furthermore, using the information
      available on the acetylation status of 100 novel proteins, we re-examined the
      rules for acetylation by NatA. The results refine our previous knowledge on NatA
      substrate specificity depending on the N-terminal and penultimate residues. In
      particular, we found that the acetylation frequencies of Ser-, Thr- and Ala-, the
      three residues most often acetylated by NatA, are higher than previously
      reported. In addition, comparison of the N-terminal region of acetylated and non
      acetylated proteins revealed differences in amino acid composition that extend
      over the 25 first amino acid residues: acetylated proteins are characterized by a
      higher frequency of glutamate and glutamine and a lower frequency of lysine,
      arginine and histidine. We suggest that the particularities in amino acid
      composition of the N-terminal region of acetylated proteins facilitate its
      interaction with the Nat1p subunit of NatA and its guidance to the catalytic
      subunit Ard1p.

PMID- 18615857
TI  - Diffusion tensor quantification of the macrostructure and microstructure of human
      midsagittal corpus callosum across the lifespan.
AB  - The midsagittal cross-sectional area of the human corpus callosum (CC) has been
      used by many researchers as a marker of development, natural aging, and
      neurodegenerative and acquired pathologies. The availability of non-invasive MRI
      methods for quantifying the macrostructural and microstructural organization of
      the CC would help to clarify the CC contribution to behavior and cognition in
      both health and disease. In this report, we extended and validated the ability of
      a recently described semi-automated diffusion tensor imaging tissue segmentation
      method to utilize the high orientation contrast of the CC on diffusion tensor
      imaging. Using a cohort of healthy right-handed children and adults aged 7-59
      years, we show gender-independent non-linear (quadratic) and strongly correlated
      growth trends in the CC area and the corresponding diffusion tensor fractional
      anisotropy (r = 0.67; P < 1 x 10(-10)). Our results provide preliminary evidence
      that diffusion tensor anisotropy in the living CC may be related to the number of
      small myelinated fibers.

PMID- 18615859
TI  - Diabetes classification: grey zones, sound and smoke: Action LADA 1.
AB  - Diseases gain identity from clinical phenotype as well as genetic and
      environmental aetiology. The definition of type 1 diabetes is clinically
      exclusive, comprising patients who are considered insulin dependent at diagnosis,
      whilst the definition of type 2 diabetes is inclusive, only excluding those who
      are initially insulin dependent. Ketosis-prone diabetes (KPD) and latent
      autoimmune diabetes in adults (LADA) are each exclusive forms of diabetes which
      are, at least initially, clinically distinct from type 2 diabetes and type 1
      diabetes, and each have a different natural history from these major types of
      diabetes.KPD can be diagnosed unequivocally as diabetes presenting with the
      categorical clinical feature, ketoacidosis. In contrast, LADA can be diagnosed by
      the co-occurrence of three traits, not one of which is categorical or exclusive
      to the condition: adult-onset non-insulin-requiring diabetes, an islet
      autoantibody such as glutamic acid decarboxylase autoantibodies (GADA) or
      cytoplasmic islet cell autoantibodies (ICA), and no need for insulin treatment
      for several months post-diagnosis. But while some would split diabetes into
      distinct subtypes, there is a strong case that these subtypes form a continuum of
      varying severity of immune and metabolic dysfunction modified by genetic and non
      genetic factors. This article discusses the nature of disease classification in
      general, and KPD and LADA in particular, emphasizing the potential value and
      pitfalls in classifying diabetes and suggesting a need for more research in this
      area.

PMID- 18615860
TI  - Mitochondrial inheritance and fermentative : oxidative balance in hybrids between
      Saccharomyces cerevisiae and Saccharomyces uvarum.
AB  - Breeding between Saccharomyces species is a useful tool for obtaining improved
      wine yeast strains, combining fermentative features of parental species. In this
      work, 25 artificial Saccharomyces cerevisiae x Saccharomyces uvarum hybrids were
      constructed by spore conjugation. A multi-locus PCR-restriction fragment length
      polymorphism (PCR-RFLP) analysis, targeting six nuclear gene markers and the
      ribosomal region including the 5.8S rRNA gene and the two internal transcribed
      spacers, showed that the hybrid genome is the result of two chromosome sets, one
      coming from S. cerevisiae and the other from S. uvarum. Mitochondrial DNA (mtDNA)
      typing showed uniparental inheritance in all hybrids. Furthermore, sibling
      hybrids, obtained by repeated crosses between the same parental strains, showed
      the same mtDNA, suggesting that the mitochondrial transmission is not stochastic
      or species-specific, but dependent on the parental strains. Finally four hybrids,
      two of which with S. cerevisiae mtDNA and two with S. uvarum mtDNA, were
      subjected to transcriptome analysis. Our results showed that the hybrids bearing
      S. cerevisiae mtDNA exhibited less expression of genes involved in
      glycolysis/fermentation pathways and in hexose transport compared to hybrids with
      S. uvarum mtDNA. Respiration assay confirmed the increased respiratory activity
      of hybrids with the S. cerevisiae mtDNA genome. These findings suggest that mtDNA
      type and fermentative : respiratory performances are correlated in S. cerevisiae
      x S. uvarum hybrids and the mtDNA type is an important trait for constructing new
      improved hybrids for winemaking.

PMID- 18615861
TI  - Assessment of blood volume, vessel size, and the expression of angiogenic factors
      in two rat glioma models: a longitudinal in vivo and ex vivo study.
AB  - Assessment of angiogenesis may help to determine tumor grade and therapy follow
      up. In vivo imaging methods for non-invasively monitoring microvasculature
      evolution are therefore of major interest for tumor management. MRI evaluation of
      blood volume fraction (BVf) and vessel size index (VSI) was applied to assess the
      evolution of tumor microvasculature in two rat models of glioma (C6 and RG2). The
      results show that repeated MRI of BVf and VSI - which involves repeated injection
      of an iron-based MR contrast agent - does not affect either the physiological
      status of the animals or the accuracy of the MR estimates of the microvascular
      parameters. The MR measurements were found to correlate well with those obtained
      from histology. They indicate that microvascular evolution differs significantly
      between the two glioma models, in good agreement with expression of angiogenic
      factors (vascular endothelial growth factor, angiopoietin-2) and with activities
      of matrix metalloproteinases, also assessed in this study. These MRI methods thus
      provide considerable potential for assessing the response of gliomas to anti
      angiogenic and anti-vascular agents, in preclinical studies as well as in the
      clinic. Furthermore, as differences between the fate of tumor microvasculature
      may underlie differences in therapeutic response, there is a need for preclinical
      study of several tumor models.

PMID- 18615862
TI  - Relatedness of medically important strains of Saccharomyces cerevisiae as
      revealed by phylogenetics and metabolomics.
AB  - Ten medically important Saccharomyces strains, comprising six clinical isolates
      of Saccharomyces cerevisiae and four probiotic strains of Saccharomyces
      boulardii, were characterized at the genetic and metabolic level and compared
      with non-medical, commercial yeast strains used in baking and wine-making.
      Strains were compared by genetic fingerprinting using amplified fragment length
      polymorphism (AFLP) analysis, by ribosomal DNA ITS1 sequencing and by metabolic
      footprinting using both direct injection mass spectrometry (DIMS) and gas
      chromatography-time of flight-mass spectrometry (GC-ToF-MS). Overall, the
      clinical isolates fell into different groupings when compared with the non
      medical strains, with good but not perfect correlation amongst strains at both
      the genetic and metabolic levels. Probiotic strains of S. boulardii that are used
      therapeutically to treat human gastro-intestinal tract disorders showed tight
      clustering both genetically and metabolically. Metabolomics was found to be of
      value both as a taxonomic tool and as a means to investigate anomalous links
      between genotype and phenotype. Key discriminatory metabolites were identified
      when comparing the three main groups of clinical, probiotic and non-medical
      strains and included molecules such as trehalose, myo-inositol, lactic acid,
      fumaric acid and glycerol 3-phosphate. This study confirmed the link between a
      subset of clinical isolates and baking or probiotic strains but also highlighted
      that in general the clinical strains were more diverse at both the genomic and
      metabolic levels.

PMID- 18615863
TI  - Marine yeasts-a review.
AB  - Yeasts are ubiquitous in their distribution and populations mainly depend on the
      type and concentration of organic materials. The distribution of species, as well
      as their numbers and metabolic characteristics were found to be governed by
      existing environmental conditions. Marine yeasts were first discovered from the
      Atlantic Ocean and following this discovery, yeasts were isolated from different
      sources, viz. seawater, marine deposits, seaweeds, fish, marine mammals and sea
      birds. Near-shore environments are usually inhabited by tens to thousands of
      cells per litre of water, whereas low organic surface to deep-sea oceanic regions
      contain 10 or fewer cells/litre. Aerobic forms are found more in clean waters and
      fermentative forms in polluted waters. Yeasts are more abundant in silty muds
      than in sandy sediments. The isolation frequency of yeasts fell as the depth of
      the sampling site is increased. Major genera isolated in this study were Candida,
      Cryptococcus, Debaryomyces and Rhodotorula. For biomass estimation ergosterol
      method was used. Classification and identification of yeasts were performed using
      different criteria, i.e. morphology, sexual reproduction and
      physiological/biochemical characteristics. Fatty acid profiling or molecular
      sequencing of the IGS and ITS regions and 28S gene rDNA ensured accurate
      identification.

PMID- 18615864
TI  - Structure elucidation of an unprecedented alkaloid and a new limonoid from
      Xylocarpus granatum.
AB  - An unprecedented new limonoid-based alkaloid, granatoine (1), and a new
      phragmalin, xylocarpin L (2), along with xyloccensin Y were isolated as minor
      components from the fruits of the Chinese mangrove plant Xylocarpus granatum.
      Their structures were elucidated by extensive spectroscopic data (1D and 2D NMR)
      analysis. A possible biogenetic pathway for granatoine was also depicted.

PMID- 18615865
TI  - A preliminary study of soft cheese degradation in different packaging conditions
      by 1H-NMR.
AB  - This preliminary work deals with the influence of packaging on the degradation of
      an Italian soft cheese studied by NMR. The NMR profiles of aqueous cheese
      extracts were acquired as a function of time during storage of cheese inside and
      outside the original package. From the NMR spectra 15 metabolites are quantified
      and used in a kinetic degradation model and in a multivariate algorithm in order
      to evaluate the changes in the metabolic composition of cheese stored under
      different conditions.

PMID- 18615868
TI  - [Alpha blockers and 5-alpha reductase inhibitors].

PMID- 18615870
TI  - [New impetus for telomerase research].

PMID- 18615871
TI  - Monitoring coping style moderates emotional reactions to genetic testing for
      hereditary nonpolyposis colorectal cancer: a longitudinal study.
AB  - OBJECTIVES: The emotional effects of genetic testing for hereditary nonpolyposis
      colorectal cancer (HNPCC) provided within a counseling program were assessed
      among 253 individuals. METHODS: Assessments were scheduled at baseline before
      testing, and again after 6 and 12 months post-test. Negative emotional reactions
      were evaluated using the Revised Impact of Event Scale and the Center for
      Epidemiological Studies-Depression Scale. Monitoring coping style was assessed at
      baseline using the Miller Behavioral Style Scale. RESULTS: Mean reductions were
      indicated in distress and depression levels within the first 6 months after
      counseling and testing. High monitors were generally more distressed than low
      monitors, specifically if they had indeterminate or positive results.
      CONCLUSIONS: Genetic counseling and testing for HNPCC do not result in long-term
      distress for most people. Of the variables investigated, only time and coping
      style have main effects on emotional reactions, and the impacts of mutation
      status are moderated by coping style. Psychological interventions, aimed to
      alleviate adverse emotional effects, were suggested for certain participants,
      i.e. recipients of positive or indeterminate results who are high monitors.

PMID- 18615873
TI  - Investigation on different levels of in vitro-in vivo correlation: gemfibrozil
      immediate release capsule.
AB  - Gemfibrozil is a practically water-insoluble, high-dose drug. It represents a
      typical drug with dissolution rate controlled bioavailability. The aim of this
      study was to select a dissolution condition for gemfibrozil immediate release
      capsules, resulting in the best in vitro/in vivo correlation (IVIVC). Five 300 mg
      gemfibrozil products, including the innovator and four generic products were
      selected. In vitro dissolution test methods with a standard paddle, round
      bottomed vessel of 1 l capacity, and potassium phosphate buffer as the
      dissolution medium (referred to as conditions I, II and III, respectively) were
      developed. The products were administered to 12 healthy volunteers and thereby
      different pharmacokinetic parameters were calculated. Correlations between the in
      vitro and in vivo calculated parameters were investigated. Of the single point
      parameters investigated, the best results were seen in the relation between the
      percent dissolved in 10, 20 and 45 min and the time to 90% dissolution from the
      in vitro side and the AUCs and C(max) from the in vivo side. The correlation
      between MRT and MDT was also investigated, and no significant correlation was
      found in the three above-mentioned conditions. The Wagner-Nelson method was used
      to calculate the percent remaining to be absorbed. Superimposition of the percent
      in vivo absorption and the in vitro dissolution curves was used to investigate a
      multiple point correlation. A remarkable superimposition between in vivo and in
      vitro curves in conditions I and II was observed.

PMID- 18615872
TI  - First-trimester uterine artery Doppler indices in term and preterm pre-eclampsia.
AB  - OBJECTIVES: To assess the relationship between first-trimester uterine artery
      Doppler measurements and the development of term and preterm pre-eclampsia.
      METHODS: This prospective study of uterine artery Doppler findings at 11-14 weeks
      in 3058 singleton pregnancies included 57 and 33 cases of term and preterm pre
      eclampsia, respectively. RESULTS: The first-trimester uterine artery resistance
      index (RI) was significantly higher in women who subsequently developed preterm
      pre-eclampsia (mean RI, 0.79) than in those with a normal outcome (mean RI, 0.70;
      P = 0.0001) or those who developed pre-eclampsia at term (mean RI, 0.72; P =
      0.002). There were no significant differences in first-trimester mean uterine
      artery RI (P = 0.136) or prevalence of bilateral notches (P = 0.459) between
      women who had a normal pregnancy outcome and those who developed pre-eclampsia at
      term. The receiver-operating characteristics curves for the prediction of term
      and preterm pre-eclampsia by uterine artery Doppler imaging demonstrated a
      significant association with development of preterm pre-eclampsia (P = 0.0001;
      area under the curve (AUC), 0.76; 95% CI, 0.66-0.86) but not term pre-eclampsia
      (P = 0.25; AUC, 0.54; 95% CI, 0.46-0.63). CONCLUSIONS: The uterine artery Doppler
      data in this study suggest that preterm pre-eclampsia is strongly associated with
      defective invasion of the spiral arteries, in contrast to the findings in term
      pre-eclampsia which may be a consequence of placental deterioration at term. Our
      study findings support, but do not prove, a rigid separation between the etiology
      of early- and late-onset pre-eclampsia. Although there is a strong relationship
      between first-trimester uterine artery Doppler indices and the subsequent
      development of preterm pre-eclampsia, our data do not support its routine
      introduction into clinical practice.

PMID- 18615874
TI  - Biomaterials and biofunctionality in layered macromolecular assemblies.
AB  - Recent research in the field of LbL assembly is summarized and categorized as
      fabrication, sensing, drug release/delivery, and cell technology. Special
      emphasis is given to topics such as cell-membrane-mimic assembly, fabrication of
      free-standing biomolecular structures including protein microtubes, detection of
      DNA adducts and reactive metabolites, DNA hybridization analysis, sensing of
      toxic and bio-active chemicals, entrapment of proteins and DNA, biocomponent
      carriers with barcode encoding, release and delivery of DNA plasmids, multiagent
      delivery, smart defense capsules and oxidation-resistant films, vector
      introduction to cells, patterned cell culturing and microfluidic microreactors,
      stem cell differentiation, cellular uptake and degradation, and control of
      cellular apoptosis.

PMID- 18615876
TI  - Filtration-based perfusion of hybridoma cultures in protein-free medium:
      Reduction of membrane fouling by medium supplementation with DNase I.
AB  - In this study, a filtration-based perfusion process was developed for the
      production of monoclonal antibodies (IgM) by suspended hybridoma cells grown in
      protein-free medium. It was found that the use of protein-free medium for
      perfusion culture generated the formation of numerous visible suspended particles
      consisting of dead cells and cellular debris aggregated into fibrous material.
      Surprisingly high apparent viabilities were observed in such protein-free
      cultures. In addition, membrane fouling occurred more rapidly in protein-free
      medium than in conventional serum-supplemented medium. By the addition of
      deoxyribonuclease I (DNase I) to the protein-free medium, it was possible to
      prevent the formation of aggregates and to follow the evolution of the total cell
      population more accurately. Moreover, DNase I significantly reduced the fouling
      of filtration membranes, and that, for two different types of separation systems
      (cross-flow and vortex-flow filtration) and two different types of membranes
      (polycarbonate and hydrophilized polysultone). From these results, it is clear
      that the presence of DNA fragments liberated following cellular death is playing
      an important role in membrane fouling. Longevity of filtration membranes was
      found to be considerably greater using a vortex-flow filtration module than with
      a static plate-and-frame cross-flow filtration module. The use of vortex-flow
      filtration of conjuction with DNase I allowed maintenance of perfusion cultures
      for more than 1 month without membrane fouling or antibody retention and with a
      constant permeate IgM concentration of 250 mg/L. Hybridomacells appeared to
      gradually adapt to increasing rotational speed in the vortex-flow filtration
      module.

PMID- 18615877
TI  - A metabolic model of cellular energetics and carbon flux during aerobic
      Escherichia coli fermentation.
AB  - An integrated metabolic model for the production of acetate by Escherichia coli
      growing on glucose under aerobic conditions was presented previously (Ko et al.,
      1993). The resulting model equations can be used to explain phenomena often
      observed with industrial fermentations, i.e., increased acetate production which
      follows from high glucose uptake rate, a low dissolved oxygen concentration, a
      high specific growth rate, or a combination of these conditions. However, several
      questions still need to be addressed. First, cell composition is growth rate and
      media dependent. Second, the macromolecular composition varied between E. coli
      strains. And finally, a model that represents the carbon fluxes between the
      Embden-Meyerhof-Parnas (EMP) and the hexose monophosphate (HMP) pathways when
      cells are subject to internal and/or external stresses is still not well defined.
      In the present work, we have made an effort to account for these effects, and the
      resulting model equations show good agreement for wild-type and recombinant E.
      coli experimental data for the acetate concentration, the onset of acetate
      secretion, and cell yield based on glucose. These results are useful for
      optimizing aerobic E. coli fermentation processes. More specifically, we have
      determined the EMP pathway carbon flux profiles required by the integrated
      metabolic model for an accurate fit of the acetic acid profile data from a wild
      type E. coli strain ML308. These EMP carbon flux profiles were correlated with a
      dimensionless measurement of biomass and then used to predict the acetic acid
      profiles for E. coli strain F-122 expressing human immunodeficiency virus
      (HIV(528)) beta-galactosidase fusion protein. The effect of different
      macromolecular compositions and growth rates between these two E. coli strains
      required a constant scaling factor for improved quantitative predictions.

PMID- 18615878
TI  - Kinetics of leucrose formation from sucrose by dextransucrase.
AB  - Leucrose formation from sucrose and fructose by dextransucrase is of practical
      interest. It has been investigated at different experimental conditions,
      including the influence of temperature on reaction rate and selectivity. Under
      appropriate conditions high product yield can be obtained. Furthermore, a model
      is presented that allows interpretation of the experimental data.

PMID- 18615879
TI  - Leuconostoc mesenteroides growth kinetics with application to bacterial profile
      modification.
AB  - Bacterial profile modification (BPM) is being developed as an oil recovery
      technique that uses bacteria to selectively plug oil depleted zones within a
      reservoir to divert displacing fluids (typically water) into oil-rich zones.
      Leuconostoc mesenteroides, which produces dextran when supplied with sucrose, is
      a bacterium that is technically feasible for use in profile modification.
      However, the technique requires controlled bacterial growth to produce selective
      plugging.A kinetic model for the production of cells and polysaccharides has been
      developed for L. mesenteroides bacteria. This model, based on data from batch
      growth experiments, predicts saccharide utilization, cell generation, and dextran
      production. The underlying mechanism is the extracellular breakdown of sucrose
      into glucose and fructose and the subsequent production of polysaccharide
      (dextran). The monosaccharides are then available for growth. Accompanying
      sucrose consumption is the utilization of yeast extract. The cell requires a
      complex media that is provided by yeast extract as a source of vitamins and amino
      acids. Varying the concentration ratio of yeast extract to sucrose in the growth
      media provides a means of controlling the amount of polymer produced per cell.
      Consequently, in situ bacteria growth can be controlled by the manipulation of
      nutrient media composition, thereby providing the ability to create an overall
      strategy for the use of L. mesenteroides bacteria for profile modification.

PMID- 18615880
TI  - Sorption and precipitation of metals in activated sludge.
AB  - A conceptual model describing the relative roles of sorption and precipitation
      processes for metals in solid-solution suspensions is presented. The model
      performance is demonstrated using experimental data on sorption and precipitation
      of metals in samples of activated sludge mixed liquor. Based on the experimental
      results presented here, it appears that, at total metal and mixed liquor
      suspended solids concentrations and pH values generally encountered in full-scale
      municipal (or combined municipal/industrial) activated sludge systems, metals are
      primarily removed by sorption processes.

PMID- 18615881
TI  - Baculovirus expression system scaleup by perfusion of high-density Sf-9 cell
      cultures.
AB  - A perfusion system based on a 4-L stirred tank bioreactor and a custom-designed
      tangential (cross-flow) filter was assembled to realize a scaleup of the
      Baculovirus Expression Vector System (BEVS). When perfused with 1 to 1.5 vol/day,
      Spodoptera frugiperda (Sf-9) insect cell cultures grew from 4 x 10(6) to 15 x
      10(6) cells/mL over 3 to 4 days. The possibility of maintaining high specific
      production of recombinant VP6 protein (from bovine rotavirus) after baculovirus
      infection of the high-density cultures was then assessed. The process consisted
      of a growth phase in TNMFH + 10% FBS, followed by infection with Bac-BRV6L
      recombinant baculovirus and a shift to a low-serum (0 to 1%) medium for perfusion
      during the production phase. Multiple runs were executed, each including a
      battery of shaker flask controls at various cell densities and serum
      concentrations. On average, specific rVP6 production in the bioreactor amounted
      to 76% of that found in 20-mL shaker cultures simulatingthe bioreactor's high
      cell density, low serum concentration, and medium renewal rate. Mechanical stress
      generated by cell/medium separation in theperfusion process reduced cell growth
      rate but had minimal effect on rVP6production. Our results also indicated that
      serum concentration during the infection phase affected the rVP6 specific
      production in a cell density-dependent fashion. Although the feasibility of the
      cell density scale up was demonstrated, optimization is still needed to achieve a
      truly cost-effective process.

PMID- 18615882
TI  - Production of poly(3-hydroxybutyric acid) by fed-batch culture of Alcaligenes
      eutrophus with glucose concentration control.
AB  - Alcaligenes eutrophus NCIMB 11599 was cultivated to produce poly(3-hydroxybutyric
      acid) (PHB) from glucose by the automatic fed-batch culture technique. The
      glucose concentration of the culture broth was controlled at 10 to 20 g/L by two
      methods: using exit gas data obtained from a mass spectrometer and using an on
      line glucose analyzer. The effect of ammonium limitation on PHB synthesis at
      different culture phases was studied. The final cell concentration, PHB
      concentration, and PHB productivity increased as ammonia feeding was stopped at a
      higher cell concentration. High concentrations of PHB (121 g/L) and total cells
      (164 g/L) were obtained in 50 h when ammonia feeding was stopped at the cell
      concentration of 70 g/L. The maximum PHB content reached 76% of dry cell weight
      and the productivity was 2.42 g/L h with the yield of 0.3 g PHB/g glucose.

PMID- 18615883
TI  - Mammalian cell damage in a novel membrane bioreactor.
AB  - The experimental study has assessed a novel membrane bioreactor for mammalian
      cell culture. In the absence of a gas phase, the key features of cell damage
      associated with laminar and turbulent flow have been identified. The bioreactor
      employs a dimpled membrane in order to enhance transverse mixing in a narrow
      channel, but a fall in viable cell density has been observed at Reynolds numbers
      above Re = 83. In the laminar flow regime wall shear is the critical mechanism
      and an accurate calculation of shear rate in a complex channel has been achieved
      using the Reynolds analogy. Flow generating a wall shear rate in excess of 3000
      s(-1) has been shown to cause damage. Power dissipation measurements have been
      used to distinguish between laminar and turbulent flow and also to predict
      Kolmogorov eddy lengths. An additional turbulent bulk stress damage mechanism at
      higher Reynolds numbers (Re > 250) results in a very rapid fall in viable cell
      density.

PMID- 18615884
TI  - Funding. Illinois launches nation's first lottery to benefit HIV/AIDS.

PMID- 18615885
TI  - Wrongful death.  Dismissal of death suit of HIV-positive offender affirmed.

PMID- 18615886
TI  - Exposure.  Physical injury absent in HIV-exposure claim.

PMID- 18615887
TI  - Disability benefits denied HIV-positive worker.

PMID- 18615888
TI  - Exposure.  Jury to reconsider disease potential from man's bite.

PMID- 18615889
TI  - Calls for further investigation into occupational exposure.

PMID- 18615890
TI  - Benefits blues.

PMID- 18615891
TI  - False aneurysm of a brachial artery in a very premature newborn.
AB  - The authors reported a case of false aneurysm in the lower third of the right
      brachial artery in a premature newborn (25 weeks of amenorrhea) subsequent to
      puncture performed 48 hours before. The treatment was surgical: resection of the
      false aneurysm and anastomosis (Monobrin 11-0 sutures) to restore the continuity
      of the brachial artery. After 6 months of follow-up, the course is favorable,
      with improvement in healing and absence of any functional disorder of the arm.

PMID- 18615892
TI  - Research from the National Institutes of Health, National Institute of Diabetes
      and Digestive and Kidney Diseases, and Charles R. Drew University of Medicine and
      Science 2007 High School Student Summer Research Program.

PMID- 18615893
TI  - Expanding the minority biomedical pipeline--the way foreward.

PMID- 18615894
TI  - Additional information on dental chew treats.

PMID- 18615895
TI  - Covering the uninsured.

PMID- 18615896
TI  - China's latest health reforms: a conversation with Chinese health minister Chen
      Zhu. Interview by Tsung-Mei Cheng.

PMID- 18615897
TI  - Does Medicare save lives?

PMID- 18615898
TI  - Poverty and health in developing countries.

PMID- 18615899
TI  - Sir Alexander Fleming.

PMID- 18615900
TI  - Soluble RAGE, diabetic nephropathy and genetic variability in the AGER gene.
AB  - Diabetes mellitus, especially when complicated with decline of renal function due
      to diabetic nephropathy (DN), is associated with accumulation of advanced
      glycation end products (AGEs) exerting their adverse effects via receptor of AGE
      (RAGE). Soluble RAGE (sRAGE) is a truncated form of RAGE functioning as an
      inhibitor of AGE-mediated signalling. We studied relationships between sRAGE,
      renal function and genetic variability in the AGER gene in diabetic subjects.
      Study comprised a total of 265 diabetics (type 1 or 2 or LADA) with
      normoalbuminuria (n = 94) or DN (n = 171). sRAGE (assessed by ELISA) was
      significantly higher in DN than normoalbuminuria subjects (P = 0.007) and
      positively correlated with age, S-urea, S-creatinine and albuminuria and AGEs
      (determined spectrofluorimetrically), negatively with GFR (all P < 0.05);
      however, multivariate regression revealed that GFR was the only independent
      variable associated with sRAGE (P = 0.047). sRAGE did not correspond with carrier
      state of risk-haplotype copies (RAGE2) (P > 0.05). In conclusion, GFR is a
      principal determinant of sRAGE concentration and gradual sRAGE increase in
      subjects with advancing impairment of renal function is paralleled by AGEs.

PMID- 18615901
TI  - Childhood obesity in Massachusetts: costs, consequences and opportunities for
      change.

PMID- 18615902
TI  - Tetanus in the equine species: a retrospective study of 31 cases.
AB  - BACKGROUND: Few studies exist about factors affecting the outcome of horses with
      tetanus. ANIMALS: 31 equids (30 horses and 1 donkey) with a clinical diagnosis of
      tetanus admitted to the Equine Clinic of the University of Liege between 1991 and
      2006. The cases were divided into two groups according to the outcome (survivors
      and non-survivors). METHODS: The clinical data of survivors and non-survivors
      were compared using an ANOVA (continuous data) or a Fisher's test (discrete
      data). RESULTS: The survival rate was 32%. Most animals were 5 years or younger,
      and none had been appropriately vaccinated. The non-survivors were significantly
      younger than the survivors. The development of dyspnoea, recumbency, and the
      combination of dysphagia, dyspnoea, and recumbency was observed significantly
      more in the non-survivors than in the survivors. The timing of tetanus antitoxin
      administration (either immediately after the onset of suggestive signs or after a
      delay) was not different between the two groups. The time between the occurrence
      of a wound and the first signs ranged from 2 days to 2 months and was not
      significantly different between groups. All non-survivors died within 8 days of
      the first signs. CONCLUSIONS & CLINICAL IMPORTANCE: This study suggests that
      young animals are affected more often and more severely by tetanus than older
      animals. Dyspnoea, recumbency, and the combination of dysphagia, dyspnoea, and
      recumbency can be considered as indicators of a poor prognosis in equids
      suffering from tetanus.

PMID- 18615903
TI  - [Prognosis, mitotic index and cell proliferation markers of mastocytoma in a
      dog].

PMID- 18615904
TI  - [Aso].

PMID- 18615905
TI  - [Ethics in practice: antibiotics in poultry].

PMID- 18615906
TI  - [Mammary health improves after participation in study groups].

PMID- 18615907
TI  - ["Breeding legislation improves the health of the entire breed"].

PMID- 18615908
TI  - [Consultation].

PMID- 18615909
TI  - Federal government delivers on their pre-election commitment to the reform of
      Australia's health care system.

PMID- 18615910
TI  - Practice nurse pap test numbers wrong.

PMID- 18615911
TI  - Indigenous demography and the regional and remote nursing workforce.

PMID- 18615912
TI  - Eight into one. National registration by 2010.

PMID- 18615913
TI  - Superannuation explained.

PMID- 18615914
TI  - Pressure ulcers--management of pressure related tissue damage.

PMID- 18615915
TI  - Nurse hits the road with new RFDS program in WA.

PMID- 18615916
TI  - Public health, ethics and HIV.

PMID- 18615917
TI  - Quality & safety in health care.

PMID- 18615918
TI  - Infection control in paediatrics.

PMID- 18615919
TI  - Nursing central line service prevents catheter related infections.

PMID- 18615920
TI  - First human transmission of bird flu.

PMID- 18615921
TI  - Nurses face challenge in flu message.

PMID- 18615922
TI  - A consumer's journey through a prostate cancer research project.

PMID- 18615923
TI  - The International Classification of Functioning, Disability and Health (ICF) is
      emerging as the principal framework for the description of health and health
      related status.

PMID- 18615924
TI  - Occupational integrity: another perspective on "life balance".
AB  - BACKGROUND: An underlying premise of occupational science and occupational
      therapy is that humans do better with a balanced lifestyle. What life balance
      means, how to design it, and to recognize when one has it have not been defined.
      PURPOSE: Our intention is to offer another perspective on life balance, one that
      we believe is at the root of what the term means. KEY ISSUES: We suggest the
      notion underlying life balance is the extent to which a person designs and lives
      in integrity with his or her own personal values, strengths and what has meaning
      for them. The term we propose is occupational integrity and that it be regarded
      as an essential precondition to life balance. IMPLICATIONS: Occupational
      integrity expands the focus of therapy beyond "doing" to interventions at the
      level of the person and identity, helping clients to identify their strengths,
      values and purpose, what is meaningful and satisfying for them, and then
      designing and living their lives in congruence with that.

PMID- 18615925
TI  - Cultural and gender effects on Israeli children's preferences for activities.
AB  - BACKGROUND: Knowledge about factors that affect participation, as preference of
      activities, has major intervention implications. PURPOSE: To evaluate culture and
      gender effects on Israeli Jewish and Druze children's preference of activities
      performed outside mandated school. This study used the "Preference Assessment of
      Children" (PAC) (King et al., 2004). FINDINGS: On most scales, the Jewish
      children showed significantly less interest in activities than the Druze
      children. Among the Jews, girls showed higher preference in most PAC scales than
      boys while among the Druze girls showed higher preference than the boys only in
      social skills. IMPLICATIONS: Culture and gender may influence children's
      preference of activity. More studies should elaborate the knowledge about
      individuals' preferred activities; understanding the factors that affect these
      preferences may enhance occupational therapy evaluation and intervention
      processes. Canadian occupational therapists, as health care professionals in a
      multicultural society, must develop cultural competency and explore people's
      experience as cultural beings.

PMID- 18615926
TI  - Living with parental multiple sclerosis: children's experiences and clinical
      implications.
AB  - BACKGROUND: Health professionals need to understand how chronic illness affects
      all family members. PURPOSE: This study explored the everyday experiences of
      children who have a parent with multiple sclerosis. METHODS: Exploratory, semi
      structured interviews were conducted with eight Queensland children, aged 7 to 14
      years. Videotapes were transcribed verbatim and analysed inductively. FINDINGS:
      Themes were labelled changing roles and responsibilities, emotional impact, and
      things that helped. Participants described taking on additional roles and
      responsibilities that restricted their participation in developmentally
      appropriate occupations, the emotional and practical impact of having a parent
      with MS and different methods they employed to cope with this impact.
      IMPLICATIONS: The findings emphasise the need for therapists to look beyond the
      diagnosed individual and see MS as a chronic illness affecting the whole family.
      Occupational therapists might assist parents and children to maintain their
      occupations through the provision of appropriate interventions and connection to
      referral networks.

PMID- 18615927
TI  - Life experiences of young adults who have coordination difficulties.
AB  - BACKGROUND: Little is known about the impact of developmental coordination
      disorder (DCD) during adolescence and young adulthood. PURPOSE: This study
      explored the lived experiences of a nonclinical sample of nine university
      students who reported having significant coordination difficulties. METHODS: A
      phenomenological approach was used that included two in-depth interviews asking
      participants to recall retrospectively their experiences throughout adolescence.
      Transcripts were coded to identify themes, and member-checking supported the
      credibility of findings. FINDINGS: Strong pathways of resilience were found with
      participants who employed cognitive and behavioural strategies to manage their
      motor differences. Key themes emerged related to managing coordination
      differences including avoidance/withdrawal/adaptation, seeking compatible
      activities, using humour, and persevering. As adolescents matured, changing
      social contexts affected their self-efficacy and others' perceptions of them.
      IMPLICATIONS: The findings of this study challenge occupational therapists to
      move beyond impairment-based interventions to ecological interventions that
      facilitate social and community participation.

PMID- 18615929
TI  - Through the eyes of students: ethical tensions in occupational therapy practice.
AB  - BACKGROUND: Many researchers have expressed concerns about ethical tensions in
      occupational therapy practice; yet little research has considered this topic from
      the perspective of students. PURPOSE: The purpose of this study was to examine
      the nature of ethical tensions witnessed or experienced by occupational therapy
      students during practice education. METHOD. A phenomenological approach was used,
      and in-depth interviews were conducted at a Canadian university with 25
      occupational therapy students. FINDINGS: Four major themes emerged from analysis
      of the data. These include systemic constraints, conflicting values, witnessing
      questionable behaviour, and failure to speak up. IMPLICATIONS: The findings of
      this study raise awareness about ethical tensions in occupational therapy
      practice witnessed or experienced by students. Critical reflection on the
      findings highlights implications for professional practice and education and
      points to the need for further research, particularly in the area of policy and
      practice.

PMID- 18615928
TI  - The wheelchair procurement process: perspectives of clients and prescribers.
AB  - BACKGROUND: Increasing choices in assistive technology have made the process of
      procuring a wheelchair more complex and challenging. PURPOSE: To explore the
      intricacies of the procurement process from the perspectives of clients and
      therapists. METHODS: Thirty-four participants were interviewed, including 13
      wheelchair prescribers, 14 wheelchair users, and 7 wheelchair associates (family
      members and caregivers). FINDINGS: Analysis revealed five main themes. "Who
      decides?" described varying degrees of client involvement in the procurement
      process. "Expert knowledge" reflected the expert knowledge that all parties
      possessed. "Form versus function"captured the primary and, at times, conflicting
      outcomes that participants wanted to achieve. "Fitting in" depicted the
      environmental factors that affected wheelchair procurement. "(Re)solutions"
      illustrated strategies that participants felt improved the process. IMPLICATIONS:
      This study reveals clients' experiences with wheelchair procurement, identifies
      potential issues therapists may encounter, and suggests possible remedies they
      might consider when prescribing wheelchairs within a client-centred framework.

PMID- 18615930
TI  - Occupational well-being: rethinking occupational therapy outcomes.
AB  - BACKGROUND: Outcomes in occupational therapy focus largely on increasing and
      enhancing the quality of clients' occupational performance, and thus, the
      importance of clients'subjective experiences of their occupations are often
      overshadowed. PURPOSE: In this paper, the concept of occupational well-being is
      introduced. Our intent is to extend the focus beyond occupational performance and
      draw attention to individuals' subjective occupational experiences. KEY ISSUES:
      We contend that occupational well-being is enhanced when individuals'
      occupational needs, including their needs for accomplishment, affirmation,
      agency, coherence, companionship, pleasure, and renewal are consistently met.
      IMPLICATIONS: Occupational therapists can play a vital role in enabling clients
      to compose or re-orchestrate their occupational lives so they are able to meet
      their occupational needs more consistently. This role may be fulfilled by
      intervening directly with clients or by indirectly influencing clients'
      occupational lives or society at large to effect changes at an environmental or
      organizational level.

PMID- 18615931
TI  - Exploring the impact of a new translation process on the performance of French
      form writers of the Canadian Certification Exam.

PMID- 18615932
TI  - Putting health promotion and prevention centre stage.

PMID- 18615933
TI  - Violence, Canadian style.

PMID- 18615934
TI  - Tobacco promotions at point-of-sale: the last hurrah.
AB  - OBJECTIVES: The retail environment provides important opportunities for tobacco
      industry communication with current, former, and potential smokers. This study
      documented the extent of tobacco promotions at the retail point-of-sale and
      examined associations between the extent of tobacco promotions and relevant city
      and store characteristics. METHODS: In each of 20 Ontario cities, 24
      establishments were randomly selected from lists of convenience stores, gas
      stations, and grocery stores. Trained observers captured the range, type and
      intensity of tobacco promotions from April to July 2005. The extent of tobacco
      promotions was described using weighted descriptive statistics. Weighted t-tests
      and ANOVAs, and hierarchical linear modeling, were used to examine the
      relationships between tobacco promotions and city and store characteristics.
      RESULTS: Extensive tobacco promotions were found in Ontario stores one year prior
      to the implementation of a partial ban on retail displays, particularly in chain
      convenience stores, gas station convenience stores and independent convenience
      stores. The multivariate hierarchical linear model confirmed differences in the
      extent of tobacco promotions by store type (p < 0.01); in addition, tobacco
      promotions were found to be higher among stores close to a school (p = 0.01) and
      in neighbourhoods with lower median household incomes (p < 0.01). Independent
      convenience stores with a greater number of employees had more tobacco
      promotions; however, the relationship was reversed for grocery stores.
      DISCUSSION: Tobacco promotions were extensive at the point-of-sale. Public health
      messages about the harms of tobacco use may be compromised by the pervasiveness
      of these promotions.

PMID- 18615935
TI  - A meta-analysis of marijuana and alcohol use by socio-economic status in
      adolescents aged 10-15 years.
AB  - OBJECTIVES: A majority of population-based studies suggest prevalence of drug and
      alcohol risk behaviour increases during late adolescence to early adulthood. The
      purpose of this systematic literature review is to clarify if socio-economic
      status (SES) is a determinant of marijuana and alcohol risk behaviour in
      adolescents between the ages of 10-15 years. METHODS: We performed a meta
      analysis to identify published or unpublished papers between January 1, 1980 and
      February 9, 2007 that reviewed marijuana and alcohol risk behaviour by SES in
      adolescents aged 10-15 years. SYNTHESIS: We found nine studies that fulfilled our
      inclusion criteria and passed the methodological quality review. The prevalence
      of marijuana and alcohol risk behaviour was 22% higher (RR = 1.22; 95% CI 1.14
      1.31) in adolescents with low SES in comparison to adolescents with higher SES.
      Stratification by country of origin revealed that American and New Zealand
      studies had statistically significant variability in the reported effects as
      compared to European and UK studies. DISCUSSION: The evidence suggests that low
      SES has an inverse association with the prevalence of marijuana and alcohol risk
      behaviour in adolescents between the ages of 10-15 years. Higher rates of
      marijuana and alcohol risk behaviour among lower SES adolescents may impact
      emotional development, limit future educational and occupational achievement, and
      increase the likelihood for adult marijuana and alcohol addiction. CONCLUSION:
      Lower SES adolescents have higher rates of marijuana and alcohol risk behaviour
      than higher SES adolescents.

PMID- 18615936
TI  - Increasing prevalence of cocaine as the primary detoxification diagnosis among
      admissions presenting with current intravenous drug use: a review of
      detoxification records from northern British Columbia, 1999-2005.
AB  - OBJECTIVES: This study sought to document the trends in drug use among
      intravenous drug users (IDUs) in northern British Columbia, and to discuss the
      public health implications. METHOD: We conducted a 7-year medical-chart review of
      all IDU-related admissions (n = 2072) to an inpatient alcohol and drug
      detoxification centre in Prince George, British Columbia. Primary detoxification
      diagnosis was modeled onto year of admission using generalized estimating
      equations (GEE). RESULTS: Our study demonstrated an increasing prevalence of
      cocaine as the primary detoxification diagnosis in IDU-related admissions in
      northern BC, from 32% of all IDU admissions in 1999 to 64% in 2001, and then a
      relatively steady elevated rate of approximately 60% between 2001-2005.
      CONCLUSIONS: Given that needle exchange programs and other harm reduction
      services for IDUs in British Columbia are not readily available in many northern
      and rural areas, the risks associated with intravenous cocaine use among northern
      IDUs represent a serious public health challenge. Tailored harm reduction
      strategies should take into account the prominence of intravenous cocaine use as
      an HIV risk factor. In areas without well-established intravenous drug use
      monitoring programs, such as rural and remote areas, detoxification treatment
      records may serve as important sentinels for changing drug use patterns among
      IDUs.

PMID- 18615937
TI  - Non-medical use of prescription opioids and public health in Canada: an urgent
      call for research and interventions development.
AB  - While the public health problem of psychoactive drug use is well recognized, the
      emerging phenomenon of non-medical use of prescription opioids has been largely
      ignored in Canada. Most evidence on this issue and related harms in North America
      to date come from the United States (US), where the prevalence of non-medical
      opioid use in key populations, as well as related morbidity and mortality,
      recently have risen substantially. Also, given the increases in the overall
      consumption of prescription opioids similar to those in the US, a substantial
      expansion of problems related to non-medical opioid use appears to be occurring
      in Canada. For example, recent major increases in the use of prescription opioids
      -rather than heroin--are documented for street drug users in Canadian cities.
      However, a comprehensive assessment of the problem of non-medical prescription
      opioid use is hindered by the spotty--or absent--nature of crucial indicators and
      data. We urge that the necessary efforts and resources for systematic assessment
      of the evolving phenomenon of non-medical opioid use and its key facets be
      established in Canada, and that policy-makers implement sensible intervention
      strategies targeting this problem within a public health framework, specifically
      avoiding unintended negative consequences (e.g., undermining access to pain
      treatment).

PMID- 18615938
TI  - Seeking sexual partners on the internet: a marker for risky sexual behaviour in
      men who have sex with men.
AB  - OBJECTIVE: In order to generate a generalizable estimate regarding risk for STI
      and HIV acquisition in men who have sex with men (MSM) who seek partners on the
      internet, we examined the sexual practices of MSM who seek partners on the
      internet compared to MSM who do not, using a community-based sample of MSM from
      British Columbia. METHODS: 'Sex Now', a questionnaire that was developed to
      examine trends in sexual behaviour in gay men, was offered to men attending Gay
      Pride events throughout the province of British Columbia, Canada between May and
      August 2004. Logistic regression analysis was used to model the association
      between seeking sexual partners online and other variables of interest, using
      odds ratio as the measure of association. RESULTS: Of the 2,312 MSM who completed
      the survey, 766 (33.1%) had used the internet to find a partner in the past year.
      In logistic regression analyses, MSM who found partners on the internet were more
      likely to have had more than 10 sexual partners in the past year (overall,
      insertive and receptive), and to engage in sexual activities in public venues.
      They were also more likely to agree with the statement "I think most guys in
      relationships have condom-free sex." MSM who sought partners on the net were more
      likely to be from specific geographic regions, including non-urban regions.
      Demographic characteristics, HIV status, and use of drugs were not significantly
      different between men who found partners on the internet and those who did not in
      multivariable modeling. DISCUSSION: MSM who sought to meet partners online had
      significantly more sexual partners, were more likely to be from specific
      geographic regions of the province and to have participated in seeking sexual
      partners in venues known to be associated with HIV and STI acquisition. This
      study confirms from a community-based sample of MSM that programming for
      prevention and treatment of HIV and STI need to be available and offered in the
      cyber setting, to ensure effective messaging and interventions reach this
      population.

PMID- 18615939
TI  - Understanding HIV viral load: implications for counselling.
AB  - This paper provides an overview of HIV viral loads in blood and genital fluids
      and how these relate to HIV transmission during sexual activity. Current
      knowledge around HIV viral loads and transmission are then discussed in relation
      to HIV disclosure laws in Canada. HIV counsellors and health care workers should
      ensure that their clients/patients are aware that blood viral load is not
      necessarily equivalent to genital tract viral load and that the development of
      drug resistance within the two compartments may be unrelated. This is an
      important factor in preventing the spread of HIV as well as for HIV-positive
      individuals in not unintentionally exposing themselves to potential legal
      repercussions.

PMID- 18615940
TI  - What's public? What's private? Policy trade-offs and the debate over mandatory
      annual influenza vaccination for health care workers.
AB  - Policy decisions about public health services differ from those for personal
      health services. Both require trade-offs between such policy goals as liberty,
      security, efficiency, and equity. In public health, however, decisions about who
      will approve, pay for, and deliver services are often accompanied by decisions on
      when and how to compel individual behaviour. Policy becomes complex because
      different stakeholders interpret evidence differently: stakeholders may assign
      different weights to policy goals and may even define the same goals differently.
      In the debate over mandatory annual influenza vaccination for health care
      workers, for example, proponents as well as opponents of mandatory vaccination
      may convey arguments in security terms. Those in favour of mandatory vaccination
      emphasize subclinical infections and duty of care (public security) while those
      opposed emphasize risk of adverse events (personal security). Proponents assert
      less worker absenteeism (efficiency) while opponents stress coercion and
      alternate personal infection control measures (liberty and individual
      rights/responsibilities). Consequently, stakeholders talk past each other.
      Determining the place of mandatory influenza vaccination for health care workers
      thus demands reconciling policy trade-offs and clarifying the underlying disputes
      hidden in the language of the policy debate.

PMID- 18615941
TI  - Long-term employment and health inequalities in Canadian communities.
AB  - OBJECTIVES: This study examines the long-term unemployment rate and various
      health outcomes across Canadian communities to estimate employment-related health
      inequalities in these communities. METHODS: The study uses cross-sectional
      community-level health data along with data on the long-term employment rate for
      various communities across Canada to quantify health inequalities among these
      communities. The health outcomes that are considered in this study include total
      and disease specific mortality rates; health conditions such as high blood
      pressure, diabetes, injuries, and self rated health; and life expectancies at
      birth and at age 65. Health inequalities are estimated using the concentration
      index, which is used to measure health inequalities along socioeconomic
      dimensions. The concentration index is estimated by a regression of weighted
      relative health (ill health) over weighted cumulative relative rank of the
      populations. All the estimates are provided separately for males and females.
      RESULTS: The findings of the study support the existence of inequalities in
      community health outcomes as related to the long-term employment rates in those
      communities. Communities with lower long term employment rates (higher
      unemployment rates) have poorer health outcomes in terms of higher mortality
      rates, worse health conditions, and shorter life expectancies. CONCLUSION: Health
      inequalities related to long-term employment have important policy implications.
      They call for policies that would increase and maintain long term employment
      rates as part of a broader socioeconomic approach to health. Long term employment
      ensures income security and prevents the psychosocial experiences leading to
      mental and physical ill health.

PMID- 18615942
TI  - Employment patterns and work injury experience among Canadian 12 to 14 year olds.
AB  - BACKGROUND: Work participation is a common activity for young adolescents. Yet it
      may impact upon other aspects of their lives and their health. We sought to
      provide some of the first Canadian population-based estimates of 12 to 14 year
      olds' employment and work injury experiences, a group typically excluded from
      labour force statistics. METHODS: Secondary data analysis of school-based surveys
      in Ontario (ON) in 2003 and British Columbia (BC) in 2005. Questions provided
      information on participation in formal and informal work during the school year,
      number of hours worked, and the occurrence of a medically attended work injury
      for students 12 to 14 years old. Different sampling strategies were accounted for
      in the analyses, including the calculation of 95% confidence intervals (CI) on
      prevalence estimates. RESULTS: Overall, 52.9% (95% CI 48.7-57.1) of ON and 41.5%
      (39.7-43.3) of BC 12 to 14 year olds reported working during the school year.
      Mean hours per week ranged from 3.3 (2.5-4.0) among Ontario 12 year olds engaged
      in non-formal work up to 11.7 (10.0-13.3) among British Columbia 14 year olds
      engaged in formal work. Work injuries were reported by 6% (4.0-8.9) of ON young
      workers and 3.5% (2.6-4.8) of BC workers. INTERPRETATION: Our findings point to
      the active presence of young adolescents in the labour market. Systematic
      approaches to active surveillance of work participation and work health and
      safety for young adolescents across Canada should be developed. Differences in
      work injury patterns by province may be worthy of further investigation.

PMID- 18615943
TI  - Public health nurses' (Phns) perceptions of their role in early postpartum
      discharge.
AB  - OBJECTIVES: Following the introduction of hospital early postpartum discharge
      (EPD), public health nurses (PHNs) have provided large-scale in-home follow-up to
      promote the safety and well-being of mothers and babies. Given high numbers of
      births per year, this program has affected PHNs' practice. This descriptive
      qualitative study aimed to explore PHNs' perceptions of EPD and its effects on
      their practice. METHODS: Data were collected in focus groups (n = 24) consisting
      of PHNs in four community health areas (CHAs) in the Winnipeg Regional Health
      Authority (WRHA). Audiotaped data were transcribed, entered into Microsoft Word
      XP, and analyzed using constant comparison. RESULTS: The female participants had
      a mean of 10 years of PHN experience. Three main themes and 10 subthemes were
      identified. The main themes were: passion for the PHN role, influence of EPD on
      practice, and building a PHN future. The subthemes included: valuing public
      health nursing, building capacity and developing relationships, changes in
      practice, erosion of health promotion, a new role, proper tools, continuity of
      care, relationships with community partners, and resources to support public
      health programs. CONCLUSION: The PHNs indicated the introduction of EPD altered
      their practice by reducing their role in community-level intervention and health
      promotion activities. Although they identified benefits from undertaking EPD
      activities, they wanted resources and funding shifted into the public health
      system to better support PHNs' increase in scope of practice and historical roles
      in promoting the health of individuals, families and communities.

PMID- 18615944
TI  - [The factors facilitating and constraining the continuation of breastfeeding in
      women in Estrie (Quebec)].
AB  - OBJECTIVE: To document breastfeeding rates from birth to six months as well as
      the factors facilitating and constraining the continuation of breastfeeding in
      women in the Eastern Townships of Quebec and to compare these to the results
      obtained in 1999. METHOD: Postal questionnaire sent to 374 mothers who had
      breastfed and analysis of archival data. RESULTS: Breastfeeding rates were 86.3%
      at birth and 75% at discharge from hospital in all mothers who gave birth to a
      child in 2004-2005. Breastfeeding rates in the 272 mothers who answered the
      questionnaire were reported to be 67.3% and 47.4% at three and six months
      respectively. Results indicate that 8.9% of infants were still receiving breast
      milk exclusively after the third month. However, 27.9% of the mothers had stopped
      breastfeeding during the infant's first week. Support from the nurses was the
      primary factor facilitating breastfeeding. The main reasons the mothers gave for
      stopping breastfeeding were problems with breastfeeding and fatigue. CONCLUSION:
      Breastfeeding rates in this area of Quebec have increased significantly in the
      past five years and are comparable with those in the rest of Canada.
      Breastfeeding exclusively up to six months is rare, and initiatives to support
      breastfeeding mothers in the hospital and in the community are having success.

PMID- 18615945
TI  - Retention of screened women in the Manitoba Breast Screening Program.
AB  - BACKGROUND: The retention rate or the percentage of women who return to screening
      within 30 months of a previous screening is an important measure of screening
      success and the acceptability of the screening program to women. The objective of
      this study was to investigate variables associated with the retention of women 50
      to 68 years of age who were screened by the Manitoba Breast Screening Program
      (MBSP) during 2002 and 2003. METHODS: All women screened by the MBSP in 2002 and
      2003 who were eligible for rescreening in 2 years were included in the study.
      Data were extracted from the MBSP database which contains demographic, screening,
      diagnostic follow-up, and diagnosis information for all women screened by the
      program. Contingency tables, chi2 tests, and logistic regression were used to
      investigate variables that were associated with retention. RESULTS: Retention was
      related to screen type (first or return), screen result (normal or abnormal),
      family history of breast cancer (risk or no risk), education (less than grade 9
      or some high school or more), and ethnicity (Asian, First Nations, other).
      Retention was not related to residence (rural or urban). CONCLUSIONS: Overall
      screening retention at the MBSP was 80% which meets national standards. However,
      additional efforts may be required to improve the retention rate of Asian and
      First Nations women as well as women who had an abnormal screening result or less
      than a grade 9 level of education.

PMID- 18615946
TI  - Are there regional differences in gynecologic cancer outcomes in the context of a
      single-payer, publicly-funded health care system? A population-based study.
AB  - BACKGROUND: Canada has a single-payer, publicly-funded health care system that
      provides comprehensive health care, and therefore significant disparities in
      health outcomes are not expected in our population. The objective of this study
      was to determine if differences exist in endometrial cancer outcomes across
      regions in Ontario. METHODS: This was a population-based study of all endometrial
      (uterine) cancer cases diagnosed from 1996 to 2000 in Ontario and linked to
      various administrative databases. Univariate analyses examined trends in
      demographics (age, income, co-morbidities), treatment (surgical staging and
      adjuvant pelvic radiotherapy), and pathology (grade, histology, stage) across 14
      geographic regions defined by local health integration networks (LHINs) in
      Ontario. Primary outcome was 5-year overall survival among LHINs, which were
      compared in a multilevel Cox regression model to account for clustering of
      patient data at the hospital level. RESULTS: There were 3,875 evaluable cases
      with complete information on demographics, treatment, pathology, and outcomes.
      There was significant variation in patient demographics, treatment, and pathology
      across the 14 LHINs. Low income level and surgery at a low-volume, community
      hospital without gynecologic oncologists were not associated with a higher risk
      of death. There was a trend towards clustering of patients within hospitals.
      After adjustment for covariates, there was no significant difference in survival
      across LHINs. CONCLUSIONS: In the context of a single-payer, publicly-funded
      health care system, we did not find significant regional differences in
      endometrial cancer outcomes.

PMID- 18615947
TI  - Health-related behaviours in adults with diabetes: associations with health care
      utilization and costs.
AB  - OBJECTIVES: The primary objective of this study was to examine whether physical
      activity, diet, and smoking behaviours are associated with health resource
      utilization and costs in the Canadian context. A secondary objective was to
      evaluate demographic and health behavioural characteristics of the participants
      of the study to assess the degree of respondent bias. METHODS: Self-reported
      physical activity, diet and smoking status were obtained from a large population
      based sample of adults with diabetes (N = 2311). Resource utilization and cost
      information was obtained by linking these data to the provincial government's
      administrative database. Multiple regression models examined predictors of
      resource utilization and costs for individuals with type 1 (T1D) and type 2 (T2D)
      diabetes separately. To assess the degree of responder bias, characteristics of
      individuals who consented to link data were compared with those who did not
      consent. RESULTS: Various measures of health care utilization and costs were
      negatively associated with physical activity behaviour in both T1D and T2D
      groups. Ever having smoked cigarettes was associated with higher resource
      utilization in individuals with T2D when controlling for demographic and health
      variables. Significant differences in demographic and health behavioural
      characteristics of the participants who provided consent for data linkage and
      those who did not were also found. CONCLUSION: These findings are of interest
      considering that PA is a critical but understudied component of individuals with
      diabetes, and this appears to be one of the first studies to directly examine the
      relationship between health-related behaviours and health care utilization and
      costs. The findings may be useful in guiding targeted health promotion programs
      for individuals with diabetes. The results also indicate that studies involving
      linkage of administrative and survey data could be over-represented by healthy
      individuals.

PMID- 18615948
TI  - Knowledge and behaviour regarding heart disease prevention in Chinese Canadian
      immigrants.
AB  - OBJECTIVE: Although Chinese are one of the fastest growing minorities in Canada,
      there is little information about heart disease prevention behaviour in Chinese
      immigrants. Our objective was to examine the knowledge and practices of Chinese
      immigrants regarding heart disease prevention. METHODS: 504 randomly selected
      Chinese adult immigrants participated in a community-based, in-person survey in
      Vancouver during 2005. The survey included questions on heart disease prevention
      knowledge and practices. RESULTS: Although respondents were quite knowledgeable
      about heart disease risk factors, their behaviours to reduce heart disease risk
      were generally low. Thirteen percent of respondents consumed five or more
      servings of fruit/vegetables per day; 37% engaged in regular physical activity;
      54% never used tobacco; 81% had received a blood pressure check in the past 2
      years; and 54% had received a cholesterol test in the past 5 years. Differences
      were found in these behaviours by gender, age, English fluency, birth country and
      duration of residence in North America. The associations are presented between
      these demographic variables and heart disease prevention behaviours. CONCLUSION:
      Heart disease prevention programs are needed in Chinese immigrant populations,
      especially aimed at increasing fruit/vegetable consumption and regular physical
      activity. Efforts are also needed to decrease tobacco use and to increase
      cholesterol testing.

PMID- 18615954
TI  - [How to improve the screening for malnutrition in elderly persons?].

PMID- 18615955
TI  - [Coordinator of an information center. Interview by Catherine Desmet].

PMID- 18615956
TI  - [Making sense of observation].

PMID- 18615957
TI  - [Is geriatrics the new Eldorado of care?].

PMID- 18615958
TI  - [Practising in geriatrics, a vocation with hazards].

PMID- 18615959
TI  - [From thinking about care to the challenges with dependent aged persons].

PMID- 18615960
TI  - [Geriatrics, a sector to support and value].

PMID- 18615961
TI  - [Valuing professional practice in geriatrics, a difficult but not impossible
      mission].

PMID- 18615962
TI  - [Continuing education in geriatrics, a privileged tool for acquiring and
      reinforcing its competences].

PMID- 18615963
TI  - [Continuing education, an opportunity to take a beneficial breath].

PMID- 18615964
TI  - [Different views of young nurses about nursing care of elderly persons. Interview
      by Tristan Cudennec].

PMID- 18615965
TI  - [3/6 -- The nurse's aide in geriatrics].

PMID- 18615966
TI  - [The Charter of the Rights and Liberties of Aged Dependent Persons].

PMID- 18615967
TI  - [Preventing falls].

PMID- 18615968
TI  - [3/6 -- Care of the painful mouth].

PMID- 18615969
TI  - Courage and character, leaders and legends: an interview with William DeVries,
      MD.

PMID- 18615970
TI  - Comparing organ donation practices and rates.

PMID- 18615971
TI  - The clinical utility of the Stress Process Model in family caregivers of liver
      transplant candidates.
AB  - This article describes the important relationship between theory and practice and
      demonstrates the application of Pearlin and colleagues' Stress Process Model to
      family caregivers of liver transplant candidates. Theory enhances the use of
      specific nursing interventions. This connection of theory to practice is
      especially important in the current health care environment, where the nursing
      shortage demands efficient and effective patient care. The Stress Process Model
      is a specific and concrete middle-range theory, which makes it simple to apply in
      clinical practice and research. This model is particularly useful for nurses who
      support the family caregivers of clients on the liver transplant list. The model
      identifies characteristics that predispose caregivers to stress that can
      interfere with completion of caregiving roles and tasks before and after
      patients' liver transplantation.

PMID- 18615972
TI  - Relationships between sex, race, and social class and social support networks in
      kidney, liver, and pancreas transplant recipients.
AB  - CONTEXT: The contribution of social support networks to the recovery of
      transplant recipients is an important assessment in measuring improved physical
      and psychosocial well-being. Social support networks are described by structure,
      type, and function. OBJECTIVES: (1) To describe the levels of structure (size,
      formal and informal support), type (concrete, emotional, and informational), and
      function (criticalness, direction, closeness, frequency, and duration) of the
      social support network and (2) to examine the relationships between individual
      characteristics of sex, race, and social class and social support networks.
      METHODS: This exploratory-descriptive study was done in a Mid-south transplant
      center. A total of 258 kidney, liver, and pancreas transplant recipients
      participated, 61% of whom were less than 50-years-old. Instruments included a
      demographic questionnaire, the social support network pie chart, and the social
      support network grid. Descriptive statistics and analysis of variance were used
      with a .05 significance level. RESULTS: The social support network comprised
      extended family (67%), with a mean of 13.68 members. Emotional support was the
      most prevalent type of support reported. The mean (SD) duration of support was
      7.9 (4.9) years. Sex, race, and social class had no main relationships with
      structure and type of support. However, women had a main effect with closeness (F
      = 4.98, P < .03) and African Americans had significantly higher levels of
      frequency of support (F = 7.51, P < .01) and longer duration of support (F =
      9.07, P < .01) than did whites. Social and nursing intervention may improve the
      network closeness in males and may also augment support frequency and duration
      for whites.

PMID- 18615973
TI  - The influence of psychosocial evaluation on candidacy for liver transplantation.
AB  - CONTEXT: Although medical factors clearly dominate the evaluation of
      appropriateness for liver transplant, psychosocial factors are an important
      dimension in the evaluation process. OBJECTIVE: To understand more about the
      weight assigned to psychosocial factors in the decision to list patients for
      liver transplant and about whether such differences create hidden inequities in
      the transplant allocation system. DESIGN: We conducted a mail survey of liver
      transplant surgeons and psychosocial evaluators at busy transplant centers
      assessing the importance these professionals assigned to psychosocial factors in
      evaluations for liver transplant candidacy. PARTICIPANTS: Liver transplant
      surgeons and psychosocial evaluators from the highest volume liver transplant
      centers in the United States. INTERVENTION: Mail survey. RESULTS: Psychosocial
      evaluators assigned greater importance to availability of transportation,
      adaptation to stress, and coping skills than did surgeons. Transplant
      psychosocial evaluators were less likely than transplant surgeons to recommend
      that a patient with a history of poor social support be listed for liver
      transplant. We found no correlation between relative weight assigned to
      psychosocial factors and median wait times at transplant centers. These
      differences suggest that the relationship between the factors identified by
      psychosocial evaluators as important and transplant outcomes should be studied.
      Overall, more research into the predictive and ethical aspects of psychosocial
      evaluation for liver transplant is needed.

PMID- 18615974
TI  - Infection, rejection, and hospitalizations in transplant recipients using
      telehealth.
AB  - CONTEXT: Telehealth technology serves individuals who live in geographical areas
      that prohibit easy access to specialized health care and can provide transplant
      recipients with access to transplant center personnel for adjunctive follow-up
      care. OBJECTIVE: To compare infection, rejection, and hospitalization events in
      subjects randomized to telehealth or to standard posttransplant care. STUDY
      DESIGN, STUDY PARTICIPANTS, SETTING AND RESEARCH PROCEDURE: This longitudinal
      prospective study compared transplant outcomes (infections, rejections, and
      hospitalizations) of 106 subjects who were randomized to either the telehealth (n
      = 53) or standard care (n = 53) group and met the 6-month study end point. Sex,
      race, and transplant type were evenly distributed within the 2 groups. Subjects
      received primary follow-up care from nurse practitioners. The telehealth visits
      were conducted via live interactive sessions with digitized equipment used to
      perform physical examinations. MAIN OUTCOMES: Infections, rejections, and
      hospitalizations were summarized for each of the groups. Subgroup analyses were
      performed by sex, transplant type, and time since transplant. RESULTS: No
      differences were found between the telehealth and standard care groups for
      infections, rejections, or hospitalizations at the 6-month data end point.
      Overall, females had twice as many infections as males (P = .01). In this
      analysis, group assignment did not affect study outcomes. CONCLUSIONS: The rates
      of infection, rejection, and hospitalization in a sample of primarily long-term
      transplant patients did not differ between patients who received telehealth
      follow-up and patients who received standard care, indicating that this delivery
      system can be used to provide follow-up care after transplant.

PMID- 18615975
TI  - An educational intervention on organ and tissue donation for first-year medical
      students.
AB  - CONTEXT: Medical students and medical professionals have knowledge deficits
      related to organ and tissue transplantation. OBJECTIVE: To implement and evaluate
      a medical education intervention on organ and tissue donation designed for first
      year medical students. STUDY DESIGN: Independent sample pretest and posttest
      design. SETTING AND PARTICIPANTS: First-year medical students attending
      University at Buffalo School of Medicine during fall 2005 and fall 2006 terms.
      INTERVENTION: A 1-hour lecture on the background of organ donation, donor
      eligibility (eg, living vs deceased donation), policies and roles during
      transplantation (eg, role of physician and organ procurement organization), and
      the organ-matching process. After the lecture, students participated in a small
      group interaction that used standardized patients who role-played 1 of 2
      scenarios designed to test students' knowledge and communication about organ and
      tissue donation. OUTCOME MEASURES: Knowledge, self-efficacy, family discussion,
      and enrollment into state organ and tissue registry. RESULTS: Significant
      increases from pretest to posttest in medical students' knowledge, self-efficacy,
      and family notification of donation intentions were found. The intervention was
      successful in increasing students' knowledge and awareness about organ and tissue
      donation. Future research should implement and evaluate a course-long curriculum
      on donation.

PMID- 18615976
TI  - Factors predictive of signed consent for posthumous organ donation.
AB  - CONTEXT: The shortage of organs for transplantation has led public health
      authorities to invest significant efforts in the promotion of organ donation.
      OBJECTIVE: To identify factors predictive of signed consent for posthumous organ
      donation by using the theory of planned behavior. PARTICIPANTS AND DESIGN: A
      random sample of 602 adults completed a questionnaire at baseline, and behavior
      was self-reported 15 months later. RESULTS: Logistic regression indicated that
      intention, perceived behavioral control, moral norm, and past behavior were
      factors predictive of consent for posthumous organ donation. Participants'
      perceived behavioral control, past behavior, and moral norm were also predictive
      of intention to sign, but attitude and perceived barriers were 2 additional
      determinants. Finally, anticipated regret and knowledge of persons who had made
      an organ donation were 2 moderators of the intention-behavior relationship.
      CONCLUSION: Overall, the results showed that intention is an important
      determinant of signing the organ donor's consent sticker and also highlighted
      that moral consideration and perceived difficulties could be 2 potential avenues
      for designing interventions.

PMID- 18615977
TI  - What does a diagnosis of brain death mean to family members approached about
      organ donation? A review of the literature.
AB  - BACKGROUND: What a diagnosis of brain stem death (the term used in the United
      Kingdom) or brain death (the term used in the United States) means to the family
      members of potential organ donors is an important issue to explore as biomedicine
      moves to expand the range of end-of-life technologies that, potentially, blur the
      demarcation between life and death. OBJECTIVE: To provide some insights into how
      a diagnosis of brain stem death or brain death may be perceived by family members
      approached about organ donation. METHODS: A review of the literature regarding
      organ donation was carried out. RESULTS: Although most publications do not focus
      specifically on the concept of brain death, those that do so made a valuable
      contribution, offering potential theoretical frameworks to aid our understanding
      of what the diagnosis of death by brain-based criteria means to family members of
      potential organ donors. The diagnosis of brain death is intricately linked to the
      issue of organ donation and may influence family members' decision making. Also,
      the perception that death has occurred differs from one person to another.
      CONCLUSIONS: A sustained increase in the number of organs available for
      transplantation may never be achieved until the concepts of brain death, brain
      stem death, and now non-heart-beating death (1) are debated more widely within
      society; (2) a greater degree of consensus is reached within health care; and (3)
      bereaved family members approached to donate the organs of their deceased
      relative have a better understanding of what these diagnoses mean.

PMID- 18615978
TI  - Intermittent antegrade cardioplegia: isolated heart preservation with the Asporto
      heart preservation device.
AB  - BACKGROUND: A major problem in procurement of donor hearts is the limited time a
      donor heart remains viable. After cardiectomy, ischemic hypoxia is the main cause
      of donor heart degradation. The global myocardial ischemia causes a cascade of
      oxygen radical formation that cumulates in an elevation in hydrogen ions
      (decrease in pH), irreversible cellular injury, and potential microvascular
      changes in perfusion. OBJECTIVE: To determine the changes of prolonged storage
      times on donor heart microvasculature and the effects of intermittent antegrade
      perfusion. MATERIALS AND METHODS: Using porcine hearts flushed with a Ribosol
      based cardioplegic solution, we examined how storage time affects microvascular
      myocardial perfusion by using contrast-enhanced magnetic resonance imaging at a
      mean (SD) of 6.1 (0.6) hours (n = 13) or 15.6 (0.6) hours (n = 11) after
      cardiectomy. Finally, to determine if administration of cardioplegic solution
      affects pH and microvascular perfusion, isolated hearts (group 1, n = 9) given a
      single antegrade dose, were compared with hearts (group 2, n = 8) given
      intermittent antegrade cardioplegia (150 mL, every 30 min, 150 mL/min) by a heart
      preservation device. Khuri pH probes in left and right ventricular tissue
      continuously measured hydrogen ion levels, and perfusion intensity on magnetic
      resonance images was plotted against time. RESULTS: Myocardial perfusion measured
      via magnetic resonance imaging at 6.1 hours was significantly greater than at
      15.6 hours (67% vs 30%, P = .00008). In group 1 hearts, the mean (SD) for pH at
      the end of 6 hours decreased to 6.2 (0.2). In group 2, hearts that received
      intermittent antegrade cardioplegia, pH at the end of 6 hours was higher at 6.7
      (0.3) (P = .0005). Magnetic resonance imaging showed no significant differences
      between the 2 groups in contrast enhancement (group 1, 62%; group 2, 40%) or in
      the wet/dry weight ratio. CONCLUSION: Intermittent perfusion maintains a
      significantly higher myocardial pH than does a conventional single antegrade
      dose. This difference may translate into an improved quality of donor hearts
      procured for transplantation, allowing longer distance procurement, tissue
      matching, improved outcomes for transplant recipients, and ideally a decrease in
      transplant-related costs.

PMID- 18615979
TI  - Psychiatric differences between liver transplant candidates with familial amyloid
      polyneuropathy and those with alcoholic liver disease.
AB  - BACKGROUND: Psychiatric diagnoses are very common in liver transplant candidates,
      and such diagnoses are predictive of a poor clinical evolution and quality of
      life after transplantation. Also, nonadherence before the transplant is
      predictive of nonadherence after the transplant. METHODS: We studied the
      psychiatric and psychosocial profiles of 85 liver transplant candidates,
      comprising consecutive patients attending outpatient clinics of a liver
      transplantation unit at a public hospital. Interviews and questionnaires were
      used to measure personality traits, symptoms of anxiety and depression, social
      support, and adherence. These patients were broken into 3 groups: patients with
      familial amyloid polyneuropathy (n = 20), patients with alcoholic liver disease
      (n = 33), and patients with other liver diseases (n = 32). RESULTS: About 58% of
      patients had a current psychiatric diagnosis (24.8%, major depressive disorder,
      22.3% generalized anxiety disorder, 8.3% adaptive disorder, 2.3% abuse of or
      dependence on substances other than alcohol). Current psychiatric diagnosis did
      not differ between patients with familial amyloid polyneuropathy and patients
      with alcoholic liver disease. Patients with alcoholic liver disease showed lower
      scores for 2 protective personality traits, social support and adherence to
      medication, than other patients. Patients with familial amyloid polyneuropathy
      showed higher scores for those traits. CONCLUSIONS: All patients waiting for a
      liver transplant should undergo psychiatric and psychological assessment. Some
      psychological characteristics such as personality traits and social support
      differ between clinical groups, so it may be useful to design different
      approaches for each group. Patients with alcoholic liver disease may require a
      special approach to improve adherence to medication.

PMID- 18615980
TI  - Health care professionals: what do they know about organ donation?
AB  - BACKGROUND: Although donor detection is influenced by the legal system and family
      refusal, underreporting due to erroneous knowledge of donation criteria and a
      lack of familiarity with the procedure among medical professionals is also a
      contributing factor. OBJECTIVE: To investigate the outlook of critical health
      professionals participating in our postgraduate courses (2001 to 2006) about
      organ donation. METHODS: We administered an in-depth survey, evaluating
      attitudes, knowledge, roles, and experiences related to organ and tissue donation
      and transplantation, to 350 participants before and after the postgraduate
      courses. RESULTS: We collected 690 surveys from 350 attendees. In the first
      survey, 280 (80%) of them showed a positive attitude toward organ donation, 210
      (60%) toward tissue donation, and 24 (7%) declared lack of knowledge about the
      subject. Only 175 (50%) had relatives who had donated organs. Sixty-three
      participants (18%) believed brain death is not equivalent to death, 176 (50%)
      claimed a lack of adequate training in this area, and 211 (60%) felt
      uncomfortable approaching families for donation. Only 88 (25%) were able to state
      the percentage of people receiving an organ in Spain, and 36 (10%) reported the
      correct number. After the course, the participants declared progress in attitudes
      toward and comfort levels with donation. Furthermore, family refusal in our
      hospital decreased from 33% to 8% to 11%. CONCLUSION: Continuous training of
      health care professionals about transplant, the legal system, and communication
      skills are crucial for successful organ and tissue donation.

PMID- 18615981
TI  - Living donors: personal perspective of a nontraditional living donor.

PMID- 18615982
TI  - AAPD and AAE symposium overview: emerging science in pulp therapy--new insights
      into dilemmas and controversies.

PMID- 18615983
TI  - The caries process and its effect on the pulp: the science is changing and so is
      our understanding.
AB  - The understanding of the caries process and its effect on the pulp is presented
      in the context that caries does develop in various rates of progression. Early in
      the caries process, the pulp reflects changes within lesion activity. Thus, the
      early pulp response is reversible. Later, the rate of caries progression is
      reflected by the quality of the tertiary dentin. Slowly progressing lesions
      create tertiary dentin resembling normal tubular dentin. Rapidly progressing
      lesions lead to the production of a tubular dentin or complete absence of
      tertiary dentin, as well as pulp necrosis and apical pathology Finally, the
      nature of the untreated deep carious lesion is on ecosystem that might undergo
      significant changes. The untreated lesion is temporarily converted from an active
      and closed lesion environment into one that is open and slowly progressing. The
      analysis of untreated carious lesions has transformed the treatment philosophy of
      deep carious lesions.

PMID- 18615984
TI  - Diagnosis dilemmas in vital pulp therapy: treatment for the toothache is
      changing, especially in young, immature teeth.
AB  - The literature is almost devoid of scientific studies of diagnosis of pulpal
      pathology in primary and permanent teeth with open apices. Most reports are
      empirical or retrospective studies without adequate prior knowledge of
      preexisting conditions or histologic findings leading to the necessity of pulpal
      procedures. Appropriate diagnostic tests and their effectiveness are documented
      for both groups. This article reviews the available literature and current
      techniques of indirect pulp therapy, pulp capping, and pulpotomy for primary
      teeth and permanent teeth with open apex. The apical barrier with mineral
      trioxide aggregate followed by root strengthening with bonded composite is
      reviewed.

PMID- 18615985
TI  - Regenerative potential of dental pulp.
AB  - The regenerative potential of dental pulp, particularly in mature teeth, has been
      considered extremely limited. However, our improved understanding of pulpal
      inflammation and repair and improved dental materials and technologies make vital
      pulp therapy a viable alternative to root canal treatment. This article explores
      our knowledge in this regard and the future potential of saving or even
      regenerating the pulp as a routine dental procedure.

PMID- 18615986
TI  - Vital pulp therapy with new materials for primary teeth: new directions and
      Treatment perspectives.
AB  - Vital pulp therapy aims to treat reversible pulpal injury and includes 2
      therapeutic approaches: (1) indirect pulp treatment for deep dentinal cavities
      and (2) direct pulp capping or pulpotomy in cases of pulp exposure. Indirect pulp
      treatment is recommended as the most appropriate procedure for treating primary
      teeth with deep caries and reversible pulp inflammation, provided that this
      diagnosis is based on a good history, a proper clinical and radiographic
      examination, and that the tooth has been sealed with a leakage-free restoration.
      Formocresol has been a popular pulpotomy medicament in the primary dentition and
      is still the most universally taught pulp treatment for primary teeth. Concerns
      have been raised over the use of formocresol in humans, and several alternatives
      have been proposed. Controlled clinical studies have been critically reviewed,
      and mineral trioxide aggregate and ferric sulfate have been considered
      appropriate alternatives to formocresol for pulpotomies in primary teeth with
      exposed pulps. In most of the studies reviewed, the caries removal method has not
      been described. The use of a high-speed handpiece or laser might result in an
      exposure of a "normal" pulp that would otherwise not be exposed.

PMID- 18615987
TI  - Vital pulp therapy with new materials: new directions and treatment perspectives-
      permanent teeth.
AB  - Pulp necrosis in immature teeth subsequent to caries has a major impact on long
      term tooth retention. The aim of vital pulp therapy is to maintain pulp viability
      by eliminating bacteria from the dentin-pulp complex and to establish an
      environment in which apexogenesis can occur. A complicating factor in treating
      immature teeth is the difficulty predicting the degree of pulpal damage. The
      ability of the clinician to manage the health of the remaining pulpal tissue
      during the procedure is paramount. Currently, the best method appears to be the
      ability to control pulpal hemorrhage by using sodium hypochlorite. Mineral
      trioxide aggregate (MTA) currently is the optimum material for use in vital pulp
      therapy. Compared with the traditional material of calcium hydroxide, it has
      superior long-term sealing ability and stimulates a higher quality and greater
      amount of reparative dentin. In the medium-term clinical assessment, it has
      demonstrated a high success rate. Thus, MTA is a good substitute for calcium
      hydroxide in vital pulp procedures.

PMID- 18615988
TI  - Indirect pulp therapy and stepwise excavation.
AB  - Various treatment concepts have been suggested to solve the deep carious lesion
      dilemma. Recent systematic reviews are presented. Their conclusions are based on
      very few studies, and the main message is that optimal randomized clinical
      studies are lacking. Observational studies on indirect pulp treatment and
      stepwise excavation demonstrate that these treatments avoid pulp exposures, but
      it cannot be said which approach is best. A less invasive modified stepwise
      excavation approach is described, focusing on changing on active lesion into on
      arrested lesion even without performing an excavation close to the pulp. In
      Denmark and Sweden a randomized clinical multi-center trial is currently taking
      place, the Caries and Pulp (CAP) trial. This trial is investigating the effects
      of stepwise excavation over 2 visits versus 1 complete excavation of deep caries
      in permanent teeth. Guidelines for treatment are presented.

PMID- 18615989
TI  - Indirect pulp capping and primary teeth: is the primary tooth pulpotomy out of
      date?
AB  - Formocresol pulpotomy (FP) in the United States is most frequently used to treat
      asymptomatic caries near the pulp in primary teeth. Indirect pulp therapy (IPT)
      is also indicated and has a significantly higher long-term success. Pulpotomy is
      thought to be indicated for primary teeth with carious pulp exposures, but
      research shows the majority of such teeth are nonvital or questionable for
      treatment with vital pulp therapy. IPT has a significantly higher success in
      treating all primary first molars, but especially those with reversible pulpitis
      compared with FP. The purpose of this article was to review the dental literature
      and new research in vital pulp therapy to determine the following: (1) Is a
      pulpotomy indicated for a true carious pulp exposure? (2) Is there a diagnostic
      method to reliably identify teeth that are candidates for vital pulp therapy? (3)
      Is primary tooth pulpotomy out of date, and should indirect pulp therapy replace
      pulpotomy? )

PMID- 18615990
TI  - Is formocresol obsolete? A fresh look at the evidence concerning safety issues.
AB  - Concern has been expressed about the safety of formocresol use in pediatric
      dentistry Formaldehyde, a primary component in formocresol, is a hazardous
      substance and is considered a probable human carcinogen by the International
      Agency for Research on Cancer, Health Canada, the Agency for Toxic Substances and
      Disease Registry in the U.S. Department of Health and Human Services, and the
      U.S. Environmental Protection Agency Humans inhale and ingest formaldehyde daily
      however, and produce formaldehyde during cellular metabolism. The human body is
      physiologically equipped to handle formaldehyde through multiple conversion
      pathways. The resultant single carbon atom released during metabolism is
      deposited in the "1-carbon pool," which, in turn, is used for the biosynthesis of
      macromolecules including DNA and RNA. Reevaluation of earlier research that
      examined potential health risks associated with formaldehyde exposure has shown
      that this research was based on flawed assumptions, which resulted in erroneous
      conclusions. The purpose of this review was to examine more recent research about
      formaldehyde metabolism, phormacokinetics, and corcinogenicity. These results
      indicated that formaldehyde is probably not a potent human carcinogen under low
      exposure conditions. Extrapolation of these research results to pediatric
      dentistry suggests an inconsequential risk associated with formaldehyde use in
      pediatric pulp therapy/

PMID- 18615991
TI  - "New age" pulp therapy: personal thoughts on a hot debate.
AB  - This article outlines the counterpoint delivered in the debate "Is Formocresol
      Obsolete?" It addresses the opinion supporting the need to move away from
      formaldehyde-containing preparations in the dental care of children. It is
      suggested that such a move should be made not just because of concerns relating
      to the possible toxicity of formaldehyde but to reflect a more contemporary,
      biologic approach to pulp therapy in the primary dentition.

PMID- 18615992
TI  - Regeneration potential of the young permanent tooth: what does the future hold?
AB  - During the last 10-15 years, there has been a tremendous increase in our clinical
      "tools" (ie, materials, instruments, and medications) and knowledge from the
      trauma and tissue engineering fields that can be applied to regeneration of a
      functional pulp-dentin complex. In addition, recent case reports indicate that
      biologically based endodontic therapies can result in continued root development,
      increased dentinal wall thickness, and apical closure when treating cases of
      necrotic immature permanent teeth. The purpose of this review was to summarize
      these findings and illustrate a path forward for the development and evaluation
      of regenerative endodontic therapies.

PMID- 18615993
TI  - Contemporary perspectives on vital pulp therapy: views from the endodontists and
      pediatric dentists.
AB  - The purpose of this study was to determine the level of agreement between
      pediatric dentists and endodontists at a pulp therapy symposium conjointly
      sponsored by the American Association of Endodontists (AAE) and the American
      Academy of Pediatric Dentistry (AAPD) on November 2-3, 2007. Presymposium and
      postsymposium tests were administered, and respondent answers were compared
      between pediatric dentists and endodontists. Opinions on 3 areas were sought:
      pulp therapy for cariously involved primary teeth; indirect pulp treatment (IPT)
      for cariously involved immature permanent teeth; and innovative treatment options
      including pulpal revascularization and regeneration. Results were analyzed with
      chi2 tests. Comparisons of presymposium and postsymposium responses and between
      the 2 groups of attendees indicated that the pediatric dentistry and endodontic
      communities agree that formocresol will be replaced as a primary tooth pulpotomy
      agent, that mineral trioxide is the first choice to take its place, that IPT in
      primary teeth holds hope as a replacement for pulpotomy, and that IPTis an
      acceptable pulp therapy technique for cariously involved young permanent teeth.
      Both groups believe that pulp revascularization and regeneration will be viable
      treatment modalities in the future. The AAE and the AAPD are positioned to begin
      preparation of best practice guidelines that share common language and treatment
      recommendations for pulp therapies performed by both specialties.

PMID- 18615994
TI  - Winners and losers in the 2009 budget.

PMID- 18615995
TI  - Independence for group practices: is it possible and desirable?
AB  - Technological advances, patient demands, pressures from payors, and change driven
      by hospitals or competing group practices combine to create a very dynamic
      practice management environment. For practice executives, these changes are
      focusing more attention on strategic and long-term planning, raising the question
      of continuing as independent private practices or considering other alternatives.
      There are several macro trends that impact the future of group practice.
      Understanding these general trends can serve as a starting point for practices to
      develop their specific roadmap to the future.

PMID- 18615996
TI  - What you do not know about disease management: a new ally in the pay-for
      performance era.
AB  - Disease management is relatively new, and many medical practices have
      misconceptions about how it works. Far from being a burden to busy medical
      practices, disease management programs can reduce hassles for physicians and
      office managers by coaching patients to be more compliant, better prepared, and
      less likely to make unnecessary phone calls. Disease management programs cost the
      medical practices nothing. They can even help practices make money by providing
      data needed for bonuses from the growing number of pay-for-performance programs.

PMID- 18615997
TI  - Not documented, not done: Medicare myth or rule?

PMID- 18615998
TI  - Lean healthcare.
AB  - As healthcare organizations look for new and improved ways to reduce costs and
      still offer quality healthcare, many are turning to the Toyota Production System
      of doing business. Rather than focusing on cutting personnel and assets, "lean
      healthcare" looks to improve patient satisfaction through improved actions and
      processes.

PMID- 18615999
TI  - Keep a pulse on practice finances.

PMID- 18616000
TI  - Primary care: life in the pressure cooker.
AB  - Primary care practices are under constant pressure of increased demand for their
      services, even as their numbers decrease. They are often scheduled to see too
      many patients in a day. Government and other third-party payors continue to
      reimburse them at a comparatively low level, despite evidence that more PCPs in
      an area improves care. Groups that want to stay in practice need to run their
      practice like a business.

PMID- 18616002
TI  - Computer briefs: the EMR, PHR, and you.

PMID- 18616001
TI  - The art of mastering the doctor-spouse work team.
AB  - An increasing number of healthcare practices are owned, managed, and staffed by
      married couples. As doctors and their spouses merge their talents to work
      together, we see a frequent outcome. While the professional alliance is
      financially and strategically sound, the nonstop reality of living and working
      together 24 hours a day, 7 days a week is putting a strain on the personal
      relationship. Following are five steps to make the alliance succeed-at work and
      at home.

PMID- 18616003
TI  - Congestive heart failure admissions: factors related to hospital length of stay.
AB  - Congestive heart failure (CHF) is an illness that affects millions of Americans
      each year; the cost associated with treatment and care is extensive. This study
      was based on a total of 480 patients admitted to the Mercy Hospital in Miami,
      Florida, during 2005. Average length of stay was significantly different based
      upon type of health insurance, race/ethnicity, marital status, admission source,
      attending physician specialty, discharge disposition, number of consultations
      while admitted, surgical procedure, and illness severity. The study results
      provide hospital executives with vital information for clinical and
      administrative CHF-related admissions management.

PMID- 18616004
TI  - Polishing your professional image: eight rules for medical practice employees.
AB  - Dress, accessories, and grooming are hugely important factors in the medical
      practice employee's professional image. But what, exactly, is professional when
      it comes to one's image, and how, specifically, can one convey professionalism to
      others? This article offers eight very specific strategies the medical practice
      employee can use to polish his or her professional image. It suggests that it is
      vital to understand what appearance says to others about you. This article offers
      guidance for practice employees wearing uniforms and those wearing business
      attire. It offers tips for being professional yet expressing one's individuality.
      Finally, this article reveals the classic signs when lack of professional attire
      is hurting one's career and provides specific tips for practice managers and
      administrators and the medical practice staff.

PMID- 18616005
TI  - Physician transition plans: planning for physician slowdown.
AB  - Transition is a natural progression for physicians in a medical practice. At some
      point, at least one physician will seek to deviate from the work norm of the
      group, either due to retirement, need for part-time status, or other reason.
      Medical practices that have a formal transition plan in place have a competitive
      advantage over other practices in terms of physician recruitment and retention.
      Not only do the formal transition plans permit physicians to proactively plan for
      work slowdown, but they also permit the medical practice to ensure its financial
      health and effectively position itself for the future. Key issues addressed in
      physician transition plans include governance, continuity of care, eligibility,
      time limits, on-call schedules, practice overhead, and physician compensation.

PMID- 18616006
TI  - It took two decades for private payor contracts to erode the bottom line: plan on
      a 2+ year comeback--here's how, part II.
AB  - In preparing to renegotiate your payor contracts, there is a series of steps to
      be followed to ensure success. In this article, we will discuss the financial
      analysis, the ever-so-important timeline that you must set and adhere to, and the
      specifics in the notice to payors that indicate that you mean business.

PMID- 18616007
TI  - Implications of Good Samaritan laws for physicians.
AB  - Good Samaritan laws are designed to encourage individuals, including physicians,
      to gratuitously render medical care in emergency situations. Through these laws,
      immunity from civil liability is provided to physicians who act in good faith to
      provide emergency care gratis. Historically, emergency care involved medical
      assistance given to persons in motor vehicle crashes or other emergency
      situations in which bystanders were present. Protection of physicians from
      allegations of negligence was a tactic of the legislative and judicial systems to
      encourage active clinical participation, rather than cautious nonparticipation,
      in emergency care. In some states and under defined circumstances, the immunity
      may apply in the hospital setting, as well as in the physician's office.
      Legislatures have continued to amend the statutes to expand the protection
      provided to physicians who offer emergency care. Judicial construction of the
      nature and scope of physician immunity has similarly expanded.

PMID- 18616008
TI  - Trends in the consumer price index.

PMID- 18616009
TI  - Triumphs and tribulations of an EMR go-live.
AB  - With customization of the electronic medical record (EMR) system winding down,
      ENT and Allergy Associates took the plunge with implementation of the system in
      its first practice location. Was the Implementation Team comfortable that the
      current status of the development was good enough to use? This article discusses
      what was learned as the EMR was unveiled for the first time.

PMID- 18616010
TI  - Financial and utilization trends in 2006.

PMID- 18616011
TI  - Inside the black box.

PMID- 18616012
TI  - No easy fix.

PMID- 18616013
TI  - Driving change.

PMID- 18616014
TI  - Easy pill to swallow.

PMID- 18616015
TI  - Not just for adults.

PMID- 18616016
TI  - MMA vision shapes health care reform.

PMID- 18616017
TI  - Gut response.

PMID- 18616018
TI  - Approach to acute, recurrent, and chronic pancreatitis.
AB  - Pancreatitis can manifest as a one-time episode, recurring attacks, or chronic
      pain. It is caused by numerous factors ranging from alcohol consumption to
      gallstones to subtle obstructive causes and occult autoimmune disorders. As a
      result, determining the etiology and effectively treating the causes and
      consequences of pancreatitis can be challenging. This article reviews the
      diagnosis and management of acute, acute recurrent, and chronic pancreatitis,
      focusing on more challenging scenarios.

PMID- 18616019
TI  - Surgeons without scalpels. A review of natural orifice translumenal endoscopic
      surgery.
AB  - Natural orifice translumenal endoscopic surgery (NOTES) is a new technique that
      allows access to the peritoneal cavity without passing through the anterior
      abdominal wall. This article reviews the evolution of NOTES and describes how it
      is currently being evaluated in animal models. It also discusses the potential
      benefits of the technique as well as the challenges it faces.

PMID- 18616020
TI  - Endoscopic ultrasound.
AB  - Endoscopic ultrasound (EUS) is being used to diagnose and evaluate a number of
      conditions of the gastrointestinal tract. This article describes the type of EUS
      equipment that is being used in clinical practice, the type of conditions for
      which it is used to diagnose and evaluate, and its therapeutic uses.

PMID- 18616021
TI  - The safety of biologic agents in the treatment of inflammatory bowel disease.
AB  - In the last decade, a new class of drugs referred to as biologics has been used
      successfully for treating patients with inflammatory bowel disease (IBD). Drugs
      such as infliximab, adalimumab, and certolizumab have been important treatment
      advancements because they allow the direct targeting of the inflammatory cytokine
      tumor necrosis factor alpha (TNF-alpha), which is elevated in the blood, stool,
      and tissue of patients with IBD. Evidence about the benefits of these drugs is
      accumulating. However, they are not risk-free, and evidence of their risks-
      primarily infection and malignancy--is also mounting. This article reviews that
      body of research and offers advice for physicians who must counsel patients about
      whether the benefits of these treatments outweigh the risks.

PMID- 18616022
TI  - Bias in the design, interpretation, and publication of industry-sponsored
      clinical research.

PMID- 18616023
TI  - Perspectives on disability.

PMID- 18616024
TI  - Nurses learn how working smarter creates time for care.

PMID- 18616025
TI  - Where is the greatest illness and disability in England?

PMID- 18616026
TI  - Partners in crime.
AB  - Working with men wh have learning disabilities and are sexual offenders can be
      gruelling. But two nurses have risen to the challenge and been named RCN Northern
      IIreland nurses of the year.

PMID- 18616027
TI  - Casualties of conflict.
AB  - Injured service personnel receive a hig stantard of rehabilitation at Headley
      Court--and nurses play a crucial role.

PMID- 18616028
TI  - Look at it this way.

PMID- 18616029
TI  - Lifting the clouds.

PMID- 18616030
TI  - The nightmare world of my coma.

PMID- 18616031
TI  - Nursing interventions to minimise undernutrition in older patients in hospital.
AB  - This information on best practice examines the evidence on effective
      interventions for use with undernourished older patients in hospital. It is based
      on an evidence synthesis of research published by Blackwell Publishing Asia and
      conducted by the Australian Centre for Evidence Based Nutrition and Dietetics
      (Vanderkroft et al 2007). The article has been reproduced with the permission of
      the Joanna Briggs Institute (JBI). The primary references are available online
      at: www.blackwell-synergy.com and to members of the JBI via the website:
      www.joannabriggs.edu.au.

PMID- 18616032
TI  - Respiratory assessment.
AB  - This article, part of Nursing Standards clinical skills series, discusses the
      'look, listen and feel' approach to respiratory assessment. This will assist
      nurses to carry out a basic respiratory assessment of the patient.

PMID- 18616033
TI  - An overview of molluscum contagiosum: a viral skin condition.
AB  - Molluscum contagiosum is a virus that causes characteristic pearly lesions on the
      surface of the skin. Small clusters of mollusca are a nuisance rather than a
      serious health problem. However, the mollusca can be more widespread and
      disfiguring in people with impaired cell-mediated immunity. Molluscum contagiosum
      virus is common in children. In adults it can also be contracted during sexual
      activity and might indicate a need for diagnostic testing for other, more serious
      sexually transmitted infections in young, sexually active adults.

PMID- 18616034
TI  - Using emollients to restore and maintain skin integrity.
AB  - Emollients are an essential treatment option for the reduction of dry skin
      conditions and the maintenance of healthy skin. These functions are dependent on
      complex interactions within the upper layers of the epidermis, designed to
      maintain the skin's dynamic but intact barrier function. Choice of emollient is
      dependent on several factors, including the variability of skin by location and
      age, as well as individual choice regarding the patient's preferred emollient
      routine.

PMID- 18616035
TI  - Academic writing.

PMID- 18616036
TI  - A love of learning.

PMID- 18616037
TI  - Keeping fit for practice.

PMID- 18616038
TI  - An end to indifference.

PMID- 18616039
TI  - Morphine: axon regeneration, neuroprotection, neurotoxicity, tolerance, and
      neuropathic pain.
AB  - Opioids have been used medicinally for millennia for their potent effects on
      nociception. However, the past 20 years have led to important insights into the
      influences and mechanisms of opioid actions, which are more extensive than merely
      analgesia, including human synthesis of opioids, critical roles of opioids during
      development and following nerve injury, and actions of different opiate alkaloids
      and their receptors. Due to the vast literature on opioids, the scope of this
      review has been limited to opioid actions in maintaining neuron viability during
      development, promoting neurological function following nerve injuries, in
      inflammation, disease and against ischemia; alleviating neuropathic pain; raising
      and lowering cellular immunity; and mechanisms modifying morphine tolerance.

PMID- 18616040
TI  - Development and validation of a questionnaire about the attitude and exposure of
      aged-Puerto Ricans to abuse and neglect.
AB  - BACKGROUND: Most studies about abuse, mistreatment and neglect of the aged have
      relied upon definitions provided by professionals and not the aged themselves
      whereas studies point out that definitions given by the aged do not correspond
      with those of professionals. Limited attention has been given to this topic in
      Puerto Rico and no studies to date have relied upon a validated and reliable
      questionnaire in Spanish for the Puerto Rican aged. OBJECTIVES: To develop and
      validate an instrument in Spanish in order to measure the opinion, attitude and
      exposure of aged Puerto Ricans to abuse, mistreatment and neglect. METHODS: A 107
      item questionnaire was developed using as a guide definitions and examples of
      abuse, mistreatment and neglect provided by the National Center on Elder Abuse of
      the United States. The sample was made up of 430 aged residing in community who
      were willing to participate. Interviews were carried out from August to December
      2004. The questionnaire scale of response was "yes" "no" and "neutral". Item
      analysis, internal consistency reliability using Cronbach's alfa index and factor
      analysis using maximum likelihood estimation technique were performed. RESULTS:
      Results showed adequate estimations of validity and reliability. The final form
      of the questionnaire was made up of 57 items of these 34 are related to attitude
      and 23 to exposure of the aged to abuse, mistreatment and neglect. CONCLUSIONS:
      The validity of the constructed instrument has been documented as least
      preliminarily. Thus this pilot study makes a contribution to the field of
      psychometric evaluation, social gerontology and related disciplines.

PMID- 18616041
TI  - Evidence-based medicine as a tool for clinical decision-making in Puerto Rico.
AB  - Evidence-based medicine (EBM) is defined as "the process of systematically
      finding, appraising and using contemporaneous research findings as the basis for
      clinical decisions". Although EBM has been extensively described across the
      Americas and Europe, no study has looked at the practice of EBM in Puerto Rico. A
      cross-sectional analysis based on a 23-item questionnaire was employed. We showed
      that there is a high use (88%) and familiarity (93%) with EBM, and that
      physicians keep a positive attitude towards EBM (80%) in Puerto Rico. There is an
      over-representation of academicians (58.9% vs. 34.6%, p = 0.02) and an under
      representation of solo office practitioners (10.5% vs. 26.9%, p = 0.03) among EBM
      users. Additionally, patient workload (48%), time constraints (36%), and limited
      access to the Internet (28%) were the most frequently cited obstacles to the
      practice of EBM in Puerto Rico. Taken together, these results help create a cross
      sectional profile of EBM practice among Puerto Rican physicians.

PMID- 18616042
TI  - Rate of weight gain in very-low birth weight Puerto Rican neonates.
AB  - BACKGROUND: Small for gestational age neonates have a higher risk of growth
      delay. The purpose of the study is to determine if there are differences in their
      early weight gain patterns that persist after adjusting for confounding
      variables. METHODS: Two-hundred sixteen neonates born between 1999 and 2003 were
      included. The group for analysis was derived by matching all the SGA infants with
      AGA infants by sex, year of birth, and birth weight. The period of observation
      was from birth to date of discharge. Weight gain rate was defined as grams gained
      per kilogram of birth weight per day. Two sample T-test was used to determine the
      difference in growth rate between the groups. Simple regression was used to
      establish the effect of morbidities on weight gain rate. RESULTS: The total mean
      birth weight was 1105 g (+/- 223 g), the mean gestational age was 30 weeks (+/-
      2.7 weeks), and the mean weight gain rate was 13.4 g/kg/d (+/- 6.8 g/kg/d). The
      mean weight gain rate for the adequate for gestational age group was lower (11.9
      g/kg/d +/- 7.6g versus 14.9 g/kg/d +/- 5.5 g) (P < 0.001). When all variables
      were analyzed using the lineal regression model, only having a low APGAR score (P
      = 0.02) and being small for gestational age (P = 0.0004) were significant.
      CONCLUSIONS: We conclude that the growth patterns of very low birth weight
      neonates are different based on the adequacy of their birth weight, and that the
      disparity in growth rate is not explained by the differences in the incidence of
      morbidities that affect growth.

PMID- 18616043
TI  - AIDS stigma combinations in a sample of Puerto Rican health professionals:
      qualitative and quantitative evidence.
AB  - The HIV/AIDS epidemic continues to impact Puerto Rico and the Caribbean region
      with growing numbers of cases each year. The stigma that surrounds the epidemic
      has harmful implications on the health of people living with the disease and
      public health in general, fostering health deterioration and new infections. When
      this stigma emanates from health professionals it can severely hinder access to
      health services, which are crucial for those living with the virus. Still, AIDS
      stigma has been previously explored among this population as a separate
      phenomenon from other pre-existing stigmas. This has yielded a limited
      perspective on the complexity of how AIDS stigma is manifested. In light of this
      limitation, the main objectives of this study were: 1) to document AIDS stigma
      among a sample of Puerto Rican health professionals and health professionals in
      training and 2) to explore the combination of other stigmas (sexism, homophobia,
      and negative attitudes towards drug users) with that associated to HIV/AIDS.
      Through an exploratory design, using a mixed method approach (qualitative in
      depth interviews and quantitative questionnaires), we explored the objectives in
      a sample of 501 health professionals and health professionals in training. The
      results evidenced the combinations of other stigmas with that of HIV/AIDS.
      Homophobia yielded the strongest correlation and was the best predictor of AIDS
      stigma. These results evidence the need to develop interventions to reduce AIDS
      stigma and its combinations among this population.

PMID- 18616044
TI  - Prevalence of overweight and obesity in a group of children between the ages of 2
      to 12 years old in Puerto Rico.
AB  - BACKGROUND: Obesity in children has been related with co-morbid conditions being
      an important risk factor in adult morbidity and mortality. The objective of this
      study was to identify the prevalence of overweight /obesity in a group of
      children in Puerto Rico. METHODS: Participants included 158 children receiving
      pediatric care at the San Juan City Hospital and a primary care clinic. Body mass
      index (BMI) was calculated in children and parents. RESULTS: Fifty-six percent of
      children were overweight/obese as well as 61% of mothers and 75% of fathers.
      Using weight-height percentiles graphs, 49% of children were overweight.
      CONCLUSIONS: This study shows the high prevalence of overweight and obesity in
      children and their parents. Using the BMI for evaluating weight identified more
      children at risk than the traditionally used graphs. Identifying risk factors
      will help health care professionals and parents intervene to improve the health
      of these families.

PMID- 18616045
TI  - Analysis of cross-reactivity between group 1 allergens from mites.
AB  - Mite allergen exposure can lead to sensitization in genetically predisposed
      individuals, and the development of asthma in previously sensitized individuals.
      The major allergens of mites belong to Dermatophagoides spp. and Blomia
      tropicalis (Bt). Various allergens of Bt have been cloned and sequenced. Some of
      them show homology sequence with purified allergens from Dermatophagoides
      pteronissynus (Dp). Recently, the allergen group 1 from Bt, Blo t 1, was cloned
      and sequenced at our laboratory. Recombinant Blo t 1 showed 35 % of identity and
      50% of similarity with group 1 allergens as Der p 1 (from Dp), Der f 1 (from D.
      farinae) and Eur m 1 (from Euroglyphus maynei) at amino acid level. This would
      suggest that cross-reactivity between allergens of different mite species could
      exist. Here, we analyzed the crossreactivity between group 1 allergens from mites
      using recombinant proteins and monoclonal antibodies against them. ELISA
      inhibition assay showed that crossreactivity between homologous allergens from
      Dermatophagoides spp. is high, but it is low to moderate between mites from
      different species. IgE-reactivity analysis using serum samples from allergic
      individuals revealed a strong reactivity of rBlo t 1 for serum samples from
      subjects with highly positive reaction to Bt extract in skin test, but lack of
      reactivity of this protein with serum samples from individuals with highly
      positive reaction to house dust mite extract in the skin test. These results
      suggest that it is important to include Bt allergens in routine skin test in
      order to improve the diagnostic accuracy and precision of allergies.

PMID- 18616046
TI  - The cerebrospinal fluid lactate is decreased in early stages of multiple
      sclerosis.
AB  - BACKGROUND: The purpose of this study was to investigate if the concentration of
      lactate can provide additional information for pathologies that need examination
      of the cerebrospinal fluid (CSF) in their diagnostic controls or protocols.
      METHODS: A prospective study carried out in the year 2001 at the University
      Hospital of Bellvitge (Barcelona), on 92 samples of CSF from patients who needed
      this examination. The concentration of lactate, glucose, and the cell count was
      determined. One year later, the diagnosis revealed from the previous analyzed
      samples were sorted into groups according to the diagnosis. RESULTS: In the group
      with multiple sclerosis (MS) (n = 30), there was a significant decrease in
      lactate concentration (1.52 +/- 0.19 mmol/L) compared to the control group (1.89
      +/- 0.11 mmol/L) (p < 0.001). The glucose concentration remained within the
      normal range and the cell count was < 4 cell/microL even in the relapses.
      CONCLUSIONS: In the early stages of MS, the lactate concentration in CSF is
      decreased and this could be related to alterations in sensitivity observed in
      those patients. Further studies are needed to evaluate if this lactate
      concentration is a prognostic indicator of the disease.

PMID- 18616047
TI  - Elimination of a pressure ulcer with electrical stimulation--a case study.
AB  - Pressure ulcers, also called decubitus ulcers, are a common challenge of humanity
      and are exceptionally difficult to heal. They are wounds that are initiated by
      relatively short periods of pressure on the skin that blocks blood circulation
      causing the skin and underlying tissues to die, leading to an open wound.
      Pressure release can prevent further tissue degeneration, and some ulcers heal
      and disappear by themselves. However, many pressure ulcers never heal and
      continue to grow in diameter and depth. By one year, such unhealing ulcers are
      referred to as chronic ulcers. Chronic ulcers frequently jeopardize the life of
      the patient due to infections that become increasingly deep until they invade
      bones and the circulatory system. We report on a patient with a chronic pressure
      ulcer at his coccyx prominence. Fourteen months after the ulcer had appeared, a
      surface pulse electromagnetic force (PEMF) stimulator was applied over T7-T8, 45
      cm cephalic to the ulcer, as part of a nerve stimulation study. Although the
      ulcer had continued to grow both in diameter and depth for 14 months and showed
      no signs of healing, within 6 days of applying the PEMF stimulator, the ulcer
      began to heal and was fully eliminated after 3 months. We concluded that the
      electrical stimulation induced the healing of the pressure ulcer. The ulcer
      elimination is quite surprising due to the exceptionally low electric field-force
      being generated by the stimulator at a distance of 45 cm.

PMID- 18616048
TI  - Flow-volume loops: clinical correlation.
AB  - Flow volume loops are an essential part of spirometry testing. Their appearance
      can give information that can be helpful in the differential diagnosis of a
      patient's clinical condition. We present two clinical scenarios in which careful
      evaluation of the flow-volume loop gives an insight into the cause of the disease
      process.

PMID- 18616049
TI  - Breast mass or sternalis muscle?
AB  - This is the first description of the sternalis muscle being found among the
      cadavers used during the last two decades in the dissection laboratories of the
      San Juan Bautista School of Medicine.

PMID- 18616050
TI  - Changing the world with words.

PMID- 18616051
TI  - Public perceptions of nursing careers: the influence of the media and nursing
      shortages.
AB  - The high public regard for nurses has not necessarily translated into an adequate
      supply of individuals who are willing to be nurses. The expected future demand
      for nurse labor challenges us to look more closely at the public's perceptions of
      nursing and nursing careers, and consider how they are shaped by personal
      experience, media messages, and socio-demographic factors. As part of ongoing
      efforts to examine factors shaping the future of the nursing workforce, a
      national survey of Americans was conducted to probe attitudes toward the nursing
      profession and their experiences with nurses. The data in this national survey of
      the public about nursing demonstrate that the nursing profession is highly
      respected and that the vast majority of the general public would recommend
      nursing careers to qualified students. If the profession is so well thought of
      and so highly recommended, why are there persistent concerns that not enough
      people are becoming RNs to avoid or at least slow down the development of future
      shortages? A prolonged and persistent effort is needed to educate people about
      nursing careers, to stimulate the expanded production of nursing faculty, and to
      bring creative approaches to financing nursing education and workforce
      improvements to convert the large number of seriously interested candidates into
      the nursing profession.

PMID- 18616053
TI  - Factors influencing work productivity and intent to stay in nursing.
AB  - The researchers document the individual and workplace characteristics associated
      with decreased work productivity and intent to stay in nursing for nurses
      employed in direct patient care in the hospital setting. Factors associated with
      decreased work productivity were age, total years worked as a RN, quality of care
      provided, job stress score, having had a job injury, and having a health problem.
      Nurse leaders must place additional efforts on changes needed to improve the
      hospital workplace environment to decrease job stress, improve RNs' ability to
      provide quality care, and to assure the health and safety of nurses. Reducing job
      stress and providing adequate staffing so quality of care can be provided will
      enhance job satisfaction which will also encourage RNs to stay at the bedside.
      Improved work environments may delay older RNs' retirement from the workforce.

PMID- 18616052
TI  - Evidence-based staffing: potential roles for informatics.
AB  - Over the last 15 years, evidence has been accumulating relating higher levels of
      nurse staffing in both quantity and experience to lower rates of adverse patient
      outcomes. Consequently, to promote quality patient outcomes efficiently, making
      staffing decisions based in evidence is of increasing importance. However, there
      is still limited data to help decide how to effectively allocate scarce nurse
      resources in practice. Existing principles, frameworks, and guidelines provide a
      foundation for nurse staffing decisions but face poor adoption. To determine
      optimal nurse staffing practices and provide evidence-based recommendations for
      policy, and integration into operations, comprehensive data are necessary.
      Information technology can assist nurse staffing decisions. Four informatics
      processes that may support evidence-based nurse staffing are described: (a) Data
      acquisition from multiple data sources, (b) Representation of data in a way it
      can be re-used for multiple purposes, (c) Sophisticated data processing and
      mining, and (d) Presentation of data in standardized and user-configurable ways.

PMID- 18616054
TI  - Localization of a demand for nursing model at the grassroots level.
AB  - A major obstacle to the development of a usable demand model for nursing is the
      standardization of the definition for "demand." The lack of standardization of
      economic terms which are utilized in the state demand models is contributing to
      the failure of the long-range forecasting process for nursing nationwide. Any
      state that chooses to utilize U.S. Department of Health and Human Services'
      Health Resources and Services Administration data has selected a model which is
      invalid due to failure to include all members of the nursing population since
      this definition excludes LPNs completely. Likewise, state nursing demand models
      in California, Pennsylvania, North Dakota, New Jersey, and the District of
      Columbia have similar disadvantages. Only at a localized county-by-county
      grassroots level can a nursing demand model be translated into an equation which
      would actually calculate demand for nursing.

PMID- 18616055
TI  - Where health care dollars are spent when pediatric palliative care is provided.
AB  - Although pediatric palliative care has become more accessible over the past
      decade, little research has been performed that focuses on the financial impact
      of providing palliative care in an inpatient hospital setting. Using a case
      controlled methodology, health care costs and the distribution of these costs
      were compared between children who received palliative care to those who did not.
      In comparing children who received palliative services to case controls, the
      similarities are striking, and the differences may have clinical significance.
      Children receiving care coordinated by the palliative care program underwent
      fewer radiology procedures and received greater assistance from pharmacologic
      services. This reflects greater attention and interventions provided to treat
      pain and provide comfort.

PMID- 18616056
TI  - Nurses' solutions to prevent inpatient falls in hospital patient rooms.
AB  - Patient fall rates are perceived as the indicator that could be most improved
      through nurse-led safety strategies or interventions. A safety-driven design with
      a goal to prevent inpatient fall-related injuries should be a hospital design
      principle. In this qualitative study, researchers used inductive and deductive
      methods to understand the clinically accessible solutions to minimize the
      extrinsic risk factors of inpatient falls. The findings from the nurse interviews
      were compared with the intervention strategies toward the five primary root
      causes of fatal falls as suggested by the Joint Commission (2005b). Twenty-four
      solutions were identified from the nurse interview transcriptions: five were
      related to the dimension of inadequate caregiver communication, none was
      associated with the dimension of inadequate staff orientation and training, three
      were related to inadequate assessment and reassessment, 15 were associated with
      unsafe care environment, and one was related to inadequate care planning and
      provision.

PMID- 18616057
TI  - How technology solutions can impact nursing retention.
AB  - In the high-tech industry, technology is at the forefront of almost all
      innovation. In health care, things move a little slower. A look at several large,
      as well as small, diverse organizations provides a snapshot of technology and its
      effect on nursing retention. Electronic medical records/computer provider order
      entry, communication via technology, facility design, staffing software, and a
      nursing innovation center are examined.

PMID- 18616058
TI  - Hospitality and service: leading real change.
AB  - A patient's decision to recommend a health care organization and the patient's
      loyalty scores are largely determined by the interaction patients and their
      families have with the nurses. Hospitality is how the delivery of that product
      makes the person feel and is a dialogue that requires the server to be "on the
      guest's side" throughout the experience. The challenge for health care is to help
      our patients and their families transcend the usual routine care of our health
      care world and to experience an emotional connection that provides that sense of
      affiliation and emotional kinship with the organization and the staff. Moving
      from the service mindset in health care to the hospitality mindset that engages
      people positively and emotionally is what healing is all about.

PMID- 18616059
TI  - The Magnet view: celebrating the Magnet way.
AB  - The Annual ANCC Magnet Conferences provide an atmosphere of learning,
      celebration, and recognition. At the 11th Annual Conference in 2007, those
      attending could choose from a variety of programs, visit exhibits, watch film
      clips from different organizations, view art displays, connect with 4,700 others
      and most of all, celebrate. Capturing the culture of this celebration and
      channeling the energy of nurses into creating solutions and a new view of nursing
      are vital to our recruitment and retention efforts.

PMID- 18616060
TI  - Making nursing-sensitive quality indicators real in ambulatory care.
AB  - Pay-for-performance initiatives are changing the quality landscape. Gaps exist in
      quantifying and linking ambulatory care quality indicators to care provided by
      nurses in ambulatory care. Ambulatory care quality indicators that are sensitive
      to nursing care, standardized, and tested need to be identified and adopted by
      ambulatory care nurses, ambulatory care provider organizations, professional
      organizations, and endorsed by a consensus organization.

PMID- 18616061
TI  - Call to arms: time to fight an epidemic.
AB  - According to the National Institutes of Health (2008), 108 million Americans are
      overweight and/or obese. In 1997, the World Health Organization noted that this
      was a major public health problem and it is no longer just an American problem.
      Clinically, nurses must find ways to have conversations with clients about weight
      and healthy lifestyles in ways that do blame the victim. Take a look at the
      vending machines for patients and their families in waiting rooms. Is there
      anything in those machines that we could consider healthy? Nurse leaders are in
      the ideal position to help their organizations consider the development and
      implementation of a wellness program. Most importantly, we have to start talking
      about the issue and find ways to develop multi-pronged approaches to confront the
      obesity epidemic.

PMID- 18616062
TI  - Medication administration: the implementation process of bar-coding for
      medication administration to enhance medication safety.
AB  - Approximately 1.5 million Americans are injured each year because of medication
      errors. In hospitals alone medication errors cost the health system well over
      $3.5 billion per year. Nurses are at the frontline of medication administration
      accountability. A Bar Code Medication Administration application was implemented
      at a 300-bed community hospital. The creation of the process was spearheaded by a
      taskforce consisting of staff nurses, nursing and pharmacy administrators, and an
      IT representative. This group planned the implementation process, which included
      changes to medication policies and procedures, downtime procedures, workflow
      designs, planning for nursing training, and changes to medication delivery. The
      results from the pilot indicated that the bar-cod technology reduced medication
      errors by 80%.

PMID- 18616063
TI  - Despite Americans' high regard, nursing shortage still looms.

PMID- 18616064
TI  - Functional diagnostics: redefining disease.

PMID- 18616065
TI  - The importance of functional biomarkers in the management of chronic illness.

PMID- 18616066
TI  - The efficacy of healing touch in coronary artery bypass surgery recovery: a
      randomized clinical trial.
AB  - CONTEXT: The use of complementary therapies in conjunction with conventional care
      has great potential to address patient pain, complication rates, and recovery
      time. Few studies of such therapies have been conducted in hospital settings
      where some of the most stressful procedures are performed on a regular basis.
      OBJECTIVE: We hypothesized that patients receiving healing touch (HT) would see
      improved outcomes. DESIGN: Patients were randomized into 1 of 3 treatment groups:
      no intervention, partial intervention (visitors), and an HT group. SETTING: This
      study was conducted in an acute-care hospital in a large metropolitan area.
      PATIENTS OR OTHER PARTICIPANTS: Patients undergoing first-time elective coronary
      artery bypass surgery were invited to participate. There were 237 study subjects.
      INTERVENTION: HT is an energy-based therapeutic approach to healing that arose
      out of nursing in the early 1980s. HT aids relaxation and supports the body's
      natural healing process. MAIN OUTCOME MEASURES: This study consisted of 6 outcome
      measures: postoperative length of stay, incidence of postoperative atrial
      fibrillation, use of anti-emetic medication, amount of narcotic pain medication,
      functional status, and anxiety. RESULTS: Analysis was conducted for all patients
      and separately by inpatient/outpatient status. Though no significant decrease in
      the use of pain medication, anti-emetic medication, or incidence of atrial
      fibrillation was observed, significant differences were noted in anxiety scores
      and length ofstay. All HT patients showed a greater decrease in anxiety scores
      when compared to the visitor and control groups. In addition, there was a
      significant difference in outpatient HT length of stay when compared to the
      visitor and control groups.

PMID- 18616067
TI  - The role of modified citrus pectin as an effective chelator of lead in children
      hospitalized with toxic lead levels.
AB  - CONTEXT: Lead toxicity is an ongoing concern worldwide, and children, the most
      vulnerable to the long-lasting effects of lead exposure, are in urgent need of a
      safe and effective heavy metal chelating agent to overcome the heavy metals and
      lead exposure challenges they face day to day. OBJECTIVE: This clinical study was
      performed to determine if the oral administration of modified citrus pectin (MCP)
      is effective at lowering lead toxicity in the blood of children between the ages
      of 5 and 12 years. METHOD: Hospitalized children with a blood serum level greater
      than 20 microg/dL, as measured by graphite furnace atomic absorption spectrometry
      (GFAAS), who had not received any form of chelating and/or detoxification
      medication for 3 months prior were given 15 g of MCP (PectaSol) in 3 divided
      dosages a day. Blood serum and 24-hour urine excretion collection GFAAS analysis
      were performed on day 0, day 14, day 21, and day 28. RESULT: This study showed a
      dramatic decrease in blood serum levels of lead (P = .0016; 161% average change)
      and a dramatic increase in 24-hour urine collection (P = .0007; 132% average
      change). CONCLUSION: The need for a gentle, safe heavy metal-chelating agent,
      especially for children with high environmental chronic exposure, is great. The
      dramatic results and no observed adverse effects in this pilot study along with
      previous reports of the safe and effective use of MCP in adults indicate that MCP
      could be such an agent. Further studies to confirm its benefits are justified.

PMID- 18616068
TI  - Is health services research the Holy Grail of complementary and alternative
      medicine research?
AB  - In a 2006 article in Alternative Therapies in Health and Medicine, Herman et al
      argued cogently that adopting a health services research (HSR) paradigm would
      help resolve some of the issues that the complementary and alternative medicine
      (CAM) community and those researching CAM face with randomized controlled trials.
      Although the article makes a strong case for HSR and CAM, it fails to discuss
      some of the work in HSR that is uniquely relevant to CAM or to provide a critique
      of the view one gets from HSR about CAM. There is within the studies of
      chiropractic a sufficient body of HSR, which can help to assess what the
      contribution of HSR has been in the past and also what its limitations are today.
      It provides a cautionary tale for CAM. This article looks at HSR in relationship
      to evidence-based practice and will discuss the limitations and dangers of the
      view of CAM from the perspective of HSR using chiropractic studies as an
      exemplar.

PMID- 18616069
TI  - Benefit of reducing whole blood viscosity for patients with angina and dementia
      symptoms.

PMID- 18616070
TI  - Melatonin for the treatment of gastroesophageal reflux disease.
AB  - The enterochromaffin cells of the gastrointestinal (GI) tract secrete 400 times
      as much melatonin as the pineal gland; therefore, it is not surprising that
      research is finding that this indole plays an important role in GI functioning.
      In animal studies, it protects against GI ulcerations, and randomized clinical
      trials suggest its efficacy in treating functional dyspepsia and irritable bowel
      syndrome. Melatonin administration has been shown to protect against esophageal
      lesions in animals. Moreover, in a randomized, single-blind clinical trial of
      subjects with gastroesophageal reflux disease (GERD), the combination of
      melatonin with other natural supplements was found to be superior to omeprazole,
      a proton pump inhibitor (PPI). Its administration as a single treatment for GERD
      has not been previously reported. A 64-year-old Caucasian female who required
      treatment with a PPI for symptoms of GERD wished to substitute a natural
      treatment because of the risk of worsening her osteoporosis. She experienced a
      return of symptoms following each of three 20-day trials of a proprietary blend
      of D-limonene when attempts were made to discontinue the PPI. She then underwent
      a trial of a natural formula consisting of melatonin 6 mg, 5-hydroxytryptophan
      100 mg, D,L-methionine 500 mg, betaine 100 mg, L-taurine 50 mg, riboflavin 1.7
      mg, vitamin B6 0.8 mg, folic acid 400 microg, and calcium 50 mg. After 40 days,
      the PPI was withdrawn without a return of symptoms. Subsequently, an attempt to
      reduce melatonin to 3 mg resulted in symptoms, while all other ingredients were
      withdrawn with minimal symptoms during 10 months of follow-up.

PMID- 18616071
TI  - Chiropractic treatment of temporomandibular disorders.

PMID- 18616072
TI  - Tracy Gaudet, MD: Turning the promise of truly integrative medicine into reality.

PMID- 18616073
TI  - Force required to luxate a newly placed dental implant in bone: an in vitro pilot
      study.
AB  - Immediate loading of newly placed dental implants is a consideration when
      attempting to meet patients' demands. However, immediate loading may induce
      implant failure to osseointegrate, particularly in the case of a patient who can
      generate a biting force that can reach approximately 1300 Newtons (N) in the
      posterior jaws. The range of biting forces that prevent osseointegration of newly
      placed implants is currently unknown. However, it is suspected that
      osseointegration may fail if an implant is luxated in bone more than 50 microm,
      in which case fibrous tissue will be formed instead of bone. This pilot study was
      focused on finding the amount of horizontal off-axial force required to move a
      nonosseointegrated 4.3 x 13-mm implant 50 microm. The initial data show that the
      amount of horizontal force required to displace such an implant by 50 microm was
      on the order of 150 N. Assuming that the angle between the direction of the
      biting force and the vertical lies between 0 degrees and 20 degrees, our data
      show that a 4.3 x 13-mm implant may fail to osseointegrate for biting forces that
      are as low as 440 N. One implication of our study is that implants having smaller
      diameters may move and fail to osseointegrate for even lower biting forces.

PMID- 18616074
TI  - Three-year analysis of tapered screw vent implants placed into maxillary sinuses
      grafted with mineralized bone allograft.
AB  - With an increase in the number of patients presenting for dental implant
      treatment, it is becoming more common for clinicians to encounter inadequate bone
      volume. Several surgical techniques have been advocated for placing dental
      implants in the posterior maxilla, including the lateral window sinus elevation
      technique. This article reports the results of implants placed into maxillary
      sinuses grafted with particulate mineralized cancellous bone allograft alone or
      in combination with resorbable hydroxyapatite over a 3-year period. A total of 56
      sinuses were grafted, and 136 dental implants were placed into the grafted sites
      after a 4- to 8-month healing period. All reentries revealed a bony hard
      structure acceptable for osteotomy preparation. Of these implants, 124 have been
      restored with fixed prosthesis and 12 with removable overdentures for a total of
      136 loaded implants. A total of 3 implants required removal (failure) resulting
      in a 97.7% implant success rate (2.3% failure rate). A conclusion was made that
      mineralized human allograft, placed into lateral window sinus elevations, is a
      clinically predicable method acceptable for implant placement and restoration.

PMID- 18616075
TI  - Technical tips for constructing a maxillary implant-supported overdenture by
      using a double-impression technique.
AB  - Implant-supported overdentures have become a popular treatment option for
      completely edentulous patients. Functional loads should be optimally distributed
      to the mucosa and the abutments. This article describes a functional double
      impression technique for fabricating a maxillary implant-supported overdenture.

PMID- 18616076
TI  - Esthetic evaluation of materials used to fill access holes of screw-retained
      implant crowns.
AB  - The access hole of screw-retained dental implant crowns presents an esthetic
      obstacle for the restorative dentist. Few if any studies have compared the
      different materials used for access hole restoration. Our objective was to
      investigate the esthetic value and acceptability of both commonly used and
      innovative access hole filling materials from the perspectives of both the
      patient and the dentist. One cement-retained crown and 5 screw-retained crowns
      were prepared on maxillary models. Access hole filling materials included dentin
      composite, resilient composite (F), enamel composite, dentin composite with
      opaquer, and resilient composite with opaquer (FO). Subjects for this study were
      recruited from a convenience sample of laypersons (n = 50) and dentists (n = 25).
      All subjects evaluated the 6 restorations on a visual analog scale (VAS) and
      determined the acceptability of each. Dentists yielded equal or higher mean
      acceptability ratings compared to laypersons for all casts; dentist ratings were
      an average of 18% more acceptable. Dentists also yielded higher mean VAS esthetic
      values on all casts, with an average value that was 7.5 points higher than that
      of laypersons. Resilient composite coupled with opaquer, compared to resilient
      composite alone, yielded improved values. Visual analog scale esthetic values
      increased from 13.8 and 24.6 (F) to 63.5 and 65.6 (FO) between laypersons and
      dentists, respectively. Acceptability improved from 12% and 36% (F) to 76% and
      88% (FO) between laypersons and dentists, respectively. Both laypersons and
      dentists are able to detect significant esthetic differences in the materials
      used to fill the access holes of screw-retained dental implants. The data showed
      that using a small amount of opaquer in combination with filling materials makes
      a significant esthetic improvement in the implant restoration.

PMID- 18616077
TI  - Retrospective clinical evaluation of tapered screw-vent implants: results after
      up to eight years of clinical function.
AB  - Uncertainty about the causes of peri-implant bone loss and difficulties in
      measuring it often have resulted in omission of bone loss data from published
      long-term implant studies. This nonrandomized, uncontrolled, retrospective study
      evaluated the clinical outcomes of treatment with tapered, multithreaded implants
      with a special emphasis on peri-implant crestal bone status. Chart reviews were
      conducted of 60 patients who had been treated with 267 implants for the placement
      of 1 or more missing and/or unsalvageable teeth, and who met general inclusion
      criteria for dental implant therapy. In all cases, marginal bone changes were
      calculated from the cementoenamel junction (CEJ) or the implant neck to the
      crestal bone level with standardized radiographs taken at implant placement
      (baseline) and during annual follow-up. After a mean followup of 7.5 years,
      implant survival was 98.5% (263/267) for all implants placed, and implant success
      was 96.2% (253/263) for all surviving implants. No discernible bone loss was
      evident in 88% of surviving implants. Crestal bone loss was observed in 25%
      (15/60) of total study subjects and in 12% (32/263) of all surviving implants: 29
      implants exhibited 1 mm of bone loss and 3 implants lost 2 mm of bone. Low
      density maxillary jawbone and more extensive bone remodeling, which were required
      around implants immediately placed into extraction sockets, were the probable
      causes of observed bone loss in this study. Implants exhibited excellent long
      term outcomes with little or no bone loss.

PMID- 18616078
TI  - Reconstruction of edentulous maxillary and mandibular arches with implant
      supported fixed restorations using a digital treatment planning technique: a
      clinical report.
AB  - This article reports on the treatment of edentulous maxillary and mandibular
      arches with implant-supported fixed partial dentures. Treatment planning and
      surgical and restorative techniques are reviewed. Preoperative computerized
      tomography was obtained and computer software was used to determine the final
      position of the implants and restorations. The outcome has been favorable both
      for the patient and the clinicians.

PMID- 18616079
TI  - Gabapentin and tinnitus relief.

PMID- 18616080
TI  - About the impact of modern knowledge, science, and medicine on neurootology.

PMID- 18616081
TI  - The role of the insula cortex in the final common pathway for tinnitus:
      experience using ultra-high-frequency therapy.
AB  - The insula cortex (Brodmann's 13-16) has distinct auditory and multisensory areas
      that have been identified through imaging to be active or hypoactive in cases of
      severe tinnitus. As such, the insula is a candidate for inclusion in the final
      common pathway (FCP) for tinnitus. The insula has connection with the prefrontal
      and auditory cortices, amygdala, thalamus, parabrachial nucleus, orbitofrontal
      cortex, striate, cuneus, and cerebellum. The insula, as part of the medial
      temporal lobe system-which also includes the amygdala and the hippocampus
      modulates its metabolic activity after high-frequency stimulation. The FCP is
      characterized by numerous areas in the lemniscal and extralemniscal pathways,
      including the auditory regions in the thalamus, the cortex, and the cerebellum.
      It is suggested that elements of the FCP, formulated into a general model of
      tinnitus, should be considered as beads on a string in designing treatment
      strategies. This view is the direct result of our past and recent new experiences
      using ultra-high-frequency sound therapy in cases of severe disabling tinnitus,
      presented at this time. Behaviorally, tinnitus symptoms decrease by self-report
      and changes in minimal masking levels with high-frequency sound therapy. The use
      of multisensory vibration stimulation (somatosensory and high-frequency jointly)
      should also be explored to maintain or reprogram the auditory cor tical map and
      induce activity in the FCP circuit, including the parabrachial nucleus and the in
      sula, which may be the physiological substrate of tinnitus behavioral tests.

PMID- 18616082
TI  - Tinnitus treatment with customized sounds.
AB  - Recent studies have indicated that the pathophysiological basis for tinnitus may
      be abnormal activity in the auditory areas of the brain rather than aberrant
      activity in the periphery. Tinnitus-related activity leads to changes in
      tonotopic representation in auditory cortex. However, such reorganization can be
      reversed through training-induced changes in the response pattern of cortical
      neurons. We address this problem by using customized sounds that reproduce the
      subjective experience to reduce overactive auditory circuits. The results of two
      preliminary studies indicate that customized sound therapy (CST*) aimed at this
      central dysfunction reduces tinnitus quickly and safely. Participants described
      immediate relief, showed changes on the Tinnitus Handicap Questionnaire, and
      reported changes in hearing threshold within 3 weeks. We also saw changes in the
      intensity dependence of the auditory N100 in tinnitus patients, supporting the
      idea that tinnitus reflects a reorganization of tonotopic maps in the auditory
      cortex. The main correlate of this reorganization was the enhanced contrast
      between responses to the perceived tinnitus pitch and tones approximately one
      octave lower. After 3 weeks of CST, the intensity dependence to the tinnitus
      pitch decreased, making these responses more similar to those from normal
      subjects responding to tones in the same frequency.

PMID- 18616083
TI  - The THI questionnaire: psychometric data for reliability and validity of the
      Italian version.
AB  - The main objective of this study was to determine reliability, validity, and
      reproducibility of the Italian version of the Tinnitus Handicap Inventory (THI)
      self-administered questionnaire aimed at evaluating the impact of tinnitus on the
      quality of life of subjects affected by this symptom. The questionnaire was
      presented to a sample of 443 subjects (285 men and 158 women; ages 19-86; mean
      age, 53) who were referred to our Tinnitus Centre in Rome and came from the
      entire national territory. All subjects reported as their main problem a tinnitus
      that had persisted for at least 6 months. Statistical analysis carried out on THI
      questionnaire results showed high internal consistency and reliability for the
      total scale (Cronbach's alpha = .94). Despite the poor number of items, the THI
      proved useful for the functional scale (0.86), the emotional scale (0.89), and
      the catastrophic scale (0.75).

PMID- 18616084
TI  - Digital craniocorpography and peripheral vestibular diseases.
AB  - Peripheral vestibular diseases (PVDs) often produce many symptoms but few or no
      measurable signs. Tests that capture and measure signs permit the comparison
      between normal and vertiginous populations. The aim of our research was to find
      movement patterns that could identify PVD patients, using a motion analysis
      laboratory. The results from 21 asymptomatic volunteers who underwent the
      Unterberger-Fukuda stepping test were compared to those of 38 PVD patients. We
      established diagnosis after a complete otoneurological workup prior to the
      stepping test. The VICON 370 (Oxford Metrics Ltd, Oxford, UK) was used for
      digital capture and analysis of the stepping tests. Lateral sway, linear and
      total displacement, shoulder height oscillation, and torticollis angle were the
      same for individuals in both groups, but stepping time, body spin, and angular
      deviation were statistically greater in those in the patient group and might help
      in the diagnosis of PVDs.

PMID- 18616085
TI  - Tinnitus: a philosophical problem.
AB  - Anatomical, physiological and metabolic properties of tinnitus have been
      identified and a comprehensive theory is immerging. The key elements and their
      interaction are presented in a general fashion highlighting areas of concern such
      as needed details of individual biosusceptibility and the need for continued
      tinnitus modeling for predictions as an aid in the development of effective
      treatment modalities. Nonetheless, there remains something of the uniqueness of
      tinnitus as a personal experience. The use of the final common pathway (FCP) as a
      unifying principle in diagnosis and treatment is presented.

PMID- 18616087
TI  - Computed tomography-based workup of conductive hearing loss with normal middle
      ear: don't forget superior semicircular canal dehiscence.
AB  - Patients with superior semicircular canal dehiscence (SSCD) may have conductive
      hearing loss (CHL) with normal middle ear (ME). A patient with CHL and normal
      tympanic membrane at otoscopy underwent tympanotomy for presumed otosclerosis but
      had negative intraoperative findings. A high-resolution computed tomography (CT)
      scan of the temporal bone performed a few years later showed the absence of
      middle-ear disorder (especially the absence of imaging signs of otosclerosis) and
      revealed a bony dehiscence of the superior semicircular canal. High-resolution CT
      scan is the test of choice for diagnosing SSCD; it mimics otosclerosis by
      manifesting itself as CHL with a normal ME. The aim of this study is to remind
      radiologists and otolaryngologists that SSCD should be systematically considered
      among the etiologies of CHL with normal ME.

PMID- 18616086
TI  - Central nervous system neurodegeneration and tinnitus: a clinical experience.
      Part II: translational neurovascular theory of neurodegenerative CNS disease and
      tinnitus.
AB  - The translation of a neurovascular hypothesis for Alzheimer's disease to
      subjective idiopathic tinnitus (SIT) is presented as a challenge to the
      predominantly sensorineural view of SIT and its clinical application for tinnitus
      treatment. The concept of neurovascular dysfunction and neurodegeneration (ND) in
      SIT patients has been proposed and reported as an etiology in a particular subset
      of tinnitus patients with a diagnosis of medical-audiological tinnitus, through a
      medical-audiological tinnitus patient protocol, to be a predominantly central
      type, severe, disabling SIT (n = 54 of 96). A medical-audiological ND tinnitus
      profile was the basis for selection of 18 SIT patients (n = 18 of 54) for nuclear
      medicine brain imaging (i.e., single-photon emission computed tomography or
      positron emission tomography, or both). Objective findings were reported in 16 of
      this cohort of 18 SIT patients selected for nuclear medicine imaging (88.9%).
      Classification of central nervous system (CNS) ND and tinnitus differentiated
      between (1) ND, nonspecific and of unknown etiology; (2) ND manifested by
      perfusion asymmetries in brain associated with ischemia (n = 11 of 18); and (3)
      ND CNS disease consistent with nuclear medicine criteria for senile dementia
      Alzheimer's-type disease (n = 5 of 18). The diagnosis was associated with
      cerebrovascular disease (n = 16 of 18). The identification of pathological
      processes of inflammation and ischemia, linked to ND, in a particular cohort of
      SIT patients may provide a basis for establishing the medical significance and
      treatment of SIT and influence the clinical course of the tinnitus.

PMID- 18616088
TI  - Treatment of vertebrobasilar insufficiency--associated vertigo with a fixed
      combination of cinnarizine and dimenhydrinate.
AB  - Thirty-seven patients suffering from vertigo associated with vertebrobasilar
      insufficiency participated in our prospective, single-center, double-blind,
      comparative study. Patients were randomly allocated to treatment with placebo;
      betahistine (12 mg betahistine dimesylate, one tablet three times daily); or the
      fixed combination of 20 mg cinnarizine and 40 mg dimenhydrinate (one tablet three
      times daily) for 4 weeks. The primary efficacy end point was the decrease of the
      mean vertigo score (S(M)), which was based on the patients' assessments of 12
      individual vertigo symptoms after 4 weeks of treatment. Patients treated with the
      fixed combination showed significantly greater reductions of S(M) as compared to
      patients receiving placebo (p < .001) or the reference therapy betahistine (p <
      .01). The vestibulospinal parameter lateral sway (Unterberger's test) improved to
      a significantly greater extent in patients taking the fixed combination as
      compared to those receiving placebo (p < .001). No serious adverse event was
      reported in any therapy group. The tolerability of the fixed combination was
      judged as very good or good by 91% (betahistine, 73%; placebo, 82%). In
      conclusion, the fixed combination proved to be statistically more effective than
      the common antivertiginous drug betahistine in reducing vertebrobasilar
      insufficiency-associated vertigo symptoms.

PMID- 18616089
TI  - Multimodal therapy for chronic tinnitus.
AB  - From 2001 to 2006, we performed a retrospective study of patients suffering from
      chronic unilateral or bilateral tinnitus that was previously ineffectively
      treated by oral drugs [betahistine (Betaserc), extract of Ginkgo biloba (EGb
      761), tanakan (Tebokan), and cinnarizine-dimenhydrinate (Arlevert), singly or in
      combination]. We divided 150 tinnitus patients (80 men, 70 women) into seven
      treatment groups. Treatments consisted of application of intravenous
      pentoxifylline, lidocaine, or vinpocetine (Cavinton) and combination of these
      agents with physiotherapy and soft laser. Mean duration (+/- standard deviation)
      of tinnitus in these patients was 7.4 +/- 6.0 years; their mean age was 55.6 +/-
      12.5 years. The aim of our study was to compare treatment modalities and define
      their effectiveness for tinnitus relief. The most effective treatment was defined
      as a combination of Cavinton and physiotherapy. We evaluated pure lidocaine
      infusion therapy as ineffective. None of the treatment modalities had an
      objective correlate of improvement, though improvement was reported by a visual
      analog scale.

PMID- 18616090
TI  - Differential outcome of a multimodal cognitive-behavioral inpatient treatment for
      patients with chronic decompensated tinnitus.
AB  - We examined 179 inpatients with severe chronic tinnitus for tinnitus-related
      distress and psychological dysfunction after treatment. We conducted a
      prospective, nonrandomized, noncontrolled study. We calculated treatment outcome
      in tinnitus-related distress, depression, and somatic complaints by analysis of
      variance with repeated measurement at admission, at discharge, and at 3, 6, and
      12 months after treatment. Additionally, on the basis of reduction in tinnitus
      related distress, responders and nonresponders were determined. We compared the
      effects of treatment for both groups on tinnitus-related distress, depression,
      and somatic complaints. In our entire sample, tinnitus-related distress,
      depression, and somatic complaints decreased significantly at discharge. After
      discharge, all patients showed improvement for up to 12 months as compared to
      their condition at admission. Of the 179 severely distressed patients, 67% were
      found to have improved clinically at discharge, and 47% still benefited after 12
      months. In comparison to the nonresponders, the responders displayed less
      depression, fewer physical complaints, and fewer body-related anxieties at each
      measuring point. The only distinguishing factors between responders and
      nonresponders were their age and the extent of their psychosocial stress.
      Limitations of the study and consequences for treatment of chronic tinnitus
      patients are discussed.

PMID- 18616091
TI  - Course of hearing recovery according to frequency in patients with acute acoustic
      sensorineural hearing loss.
AB  - Through pure-tone audiometry, we studied the course of hearing recovery in 24
      ears of 20 men (ages 18-48 years) who had acute acoustic sensorineural hearing
      loss (ASHL). All subjects were members of the Japanese Self-Defense Force. The
      hearing level in 5 ears returned to normal, the hearing level of 13 ears
      recovered but was not within the normal range, and the hearing level of 6 ears
      was unchanged. The time from noise exposure to presentation was longer in
      patients with unchanged hearing than in other patients. Recovery of hearing was
      poorest at 4,000 Hz, followed by 8,000 and 2,000 Hz. We concluded that hearing in
      patients with acute ASHL is likely to return to normal when the hearing level at
      4,000 Hz recovers gradually; partial recovery of hearing is expected when the
      hearing level at 4,000 Hz reaches an early plateau.

PMID- 18616092
TI  - [Indication for limited surgery on small lung cancer tumors measuring 1cm or less
      in diameter on preoperative computed tomography and long-term results].
AB  - OBJECTIVE: Non-invasive lung cancers showed a good prognosis after limited
      surgery. But it is still uncertain about invasive lung cancers. We investigated
      the indications for limited surgery for small lung cancer tumors measuring 1 cm
      or less in diameter on preoperative computed tomography (CT). METHODS: This study
      retrospectively analyzed of 1,245 patients who underwent complete resection of
      lung cancer between 1989 and 2004 in our hospital. Sixty-two patients (5%) had
      tumors measuring 1 cm or less in diameter. The probability of survival was
      calculated using the Kaplan-Meier method. RESULTS: All diseases were detected by
      medical checkup, 52 % of the patients were not definitively diagnosed with lung
      cancer before surgery. Adenocarcinoma was histologically diagnosed in 49 patients
      (79%). Other histologic types included squamous cell carcinoma (8), large cell
      carcinoma (1), small cell carcinoma (1), carcinoid (2), and adenosquamous cell
      carcinoma (1). Fifty-seven patients (92%) showed pathologic stage IA. The other
      stages were IB (2), IIA (1), and IIIB (2). There were 14 bronchioloalveolar
      carcinomas (25% of IA diseases). The 5-year survival rates of IA patients were
      90%. The 5-year survival rate of patients with tumors measuring 1cm or less
      diameter was 91% after lobectomy or pneumonectomy, and 90% after wedge resection
      or segmentectomy. There were 3 deaths from cancer recurrence, while there were no
      deaths in 14 patients with bronchioloalveolar carcinoma CONCLUSION: After limited
      surgery, non-invasive cancer showed good long-term results, while invasive cancer
      showed a recurrence rate of 2.3% to 79% even though the tumor measured 1 cm or
      less in diameter on preoperative CT.

PMID- 18616093
TI  - [Indication and timing of surgical intervention for cardiovascular disease in
      hemodialysis dependent patients].
AB  - Surgical intervention on cardiovascular disorders in patients with hemodialysis
      dependent renal failure improves their life expectancy, but carries high surgical
      mortality. Decision on the indication of surgery as well as on its timing has
      crucial impact on surgical outcome. We retrospectively analyzed the data of 21
      hemodialysis dependent patients who had undergone cardiovascular surgery in our
      institution from May 2001 to May 2005 to elucidate the appropriate indication and
      timing of surgical intervention. The study revealed early mortality (< 30 days)
      of 4.8% and 5 year survival rate of 83.5%. Risk factors for poor prognosis were
      older age, and longer hemodialysis history. Despite the opinions advocating early
      surgery in these patients, we adopted a surgical strategy to wait until patients'
      condition is optimized. Low surgical mortality and high long-term survival of our
      surgical series indicated appropriateness of our strategy on the timing of
      surgery. However, extremely low long-term mortality rate raised the concern that
      our surgical indication might have been too conservative.

PMID- 18616094
TI  - [Evaluation of a new portable device for measuring prothrombin time-internatinal
      normalized ratio; comparison between the conventional method and the new
      CoagCheck XS].
AB  - We evaluated a new portable device (CoaguCheck XS) for measuring the prothrombin
      time-international normalized ratio (PT-INR) in 63 patients after cardiac
      surgery, and compared the results with those of the conventional method. There
      was a good correlation between the PT-INR values measured conventionally and
      those obtained with the CoaguCheck XS. This new device was easy to use, data were
      obtained rapidly, and the results were reliable. The CoaguCheck XS will be
      particularly useful for outpatients. PT-INR self-management is expected to be
      introduced as soon as health insurance coverage is obtained.

PMID- 18616095
TI  - [Atrial rupture due to blunt chest trauma].
AB  - Atrial rupture by blunt trauma is lethal and one of controversial problems for
      cardiovascular surgeons, because of complexed conditions due to multiple organ
      injuries. Some papers recommend strategy of early diagnosis and treatment at an
      acute phase for better clinical course, but high mortality rate has not been
      improved yet, especially that of left atrial rupture. Three patients were
      reffered to our hospital by blunt chest trauma, one of whom died due to
      hemorrhagic shock before receiving surgical or interventional treatment. The
      remaining 2 patients had surgical operations at an early phase and were
      discharged without severe complications. We review our strategy of atrial rupture
      of blunt chest trauma. At an acute phase, atrial rupture alone should be repaired
      urgently unless use of cardiopulmonary bypass is contraindicated by severe
      hemorrhage of the other organs.

PMID- 18616096
TI  - [Congenital bronchoesophageal fistula in an adult; an undiscribed mechanism of
      symptom tolerance].
AB  - We present a case of a congenital bronchoesophageal fistula in a 61-year-old
      woman. She was referred to hospital because of postprandial heart burn. Three
      dimensional (3D) computed tomography (CT) demonstrated an anastomosis between her
      right intermediate bronchus and esophagus. In spite of direct communication
      between her bronchus and esophagus, she has never suffered severe infection. We
      visualized the orifice of fistula closed with mucosal flap in swallowing by means
      of a bronchofiberscope. The delay of a diagnosis was explained by symptom
      tolerance. Some theories as to the symptom tolerance are found in literatures,
      but we supposed to find an undiscribed mechanism; closure of the orifice in
      swallowing. The fistula was surgically closed.

PMID- 18616097
TI  - [Pulmonary metastasis of metachronous triple cancer occurring in a young
      patient].
AB  - A 24-year-old patient who developed pulmonary metastasis of metachronous triple
      cancer was presented. She had undergone surgery and combined chemotherapy for
      osteosarcoma of the right humerus in 1993. Then, she was followed-up without any
      sign of recurrence. She felt accidentally a lump of the right breast so she had
      visited a hospital for a work-up in 2004. The detailed examination proved that
      the right breast mass was primary breast cancer so the right mastectomy was
      carried out. Moreover, the left mastectomy was also carried out for the primary
      breast cancer in 2005. Additionally, a solitary nodule shadow was detected by
      computed tomography in 2007 so she had thoracoscopic partial resection of right
      middle lobe. Histopathologically, the tumor was diagnosed metastasis from the
      left breast cancer. It is unlikely that familial cancer disease was the
      underlying cause because she had no family history of cancer. A more likely
      explanation is that there is the influence of combined chemotherapy during
      puberty.

PMID- 18616098
TI  - [Reoperation due to failure of a Freestyle bioprosthesis].
AB  - We report re-do aortic valve and ascending aorta replacements by using the valve
      on-valve technique for primary tissue failure of a Freestyle bioprosthesis. A 74
      year-old male, who had had a 25 mm Freestyle bioprosthetic valve implanted by the
      sub-coronary method 5 years previously for aortic valve regurgitation due to
      congenital bicuspid valve, was referred to our hospital for dyspnea and
      palpitation. He presented with heart failure secondary to aortic regurgitation
      due to primary tissue failure, and computed tomography demonstrated an enlarged
      ascending aorta (5 cm in diameter). The operative findings revealed that the
      Freestyle bioprosthetic valve had a leaflet tear at the left coronary cusp. We
      replaced the degenerated Freestyle bioprosthesis with a 19 mm Mosaic aortic
      bioprosthesis by using the valve-on-valve technique, and ascending aorta
      replacement was performed simultaneously. This technique can be useful for re-do
      surgery for degenerated stentless valves to avoid potential risks of complete
      excision of the bioprosthesis.

PMID- 18616099
TI  - [Aortic valve replacement through right anterolateral thoracotomy for aortic
      stenosis after mediastinal radiation therapy].
AB  - A 76-year-old woman had severe aortic stenosis on transthoracic echocardiography
      [aortic valve area (AVA): 0.7 cm2, max pressure gradient (PG): 108 mmHg]. Since
      she was on radiation therapy for breast cancer, we considered that median
      sternotomy was a risk factor for mediastinitis, and right thoracotomy was chosen
      for aortic valve replacement. The operation was performed through a right
      anterolateral thoracotomy. Cardiopulmonary bypass was established with right
      femoral artery cannulation, right atrial cannulation, and right superior
      pulmonary vein cannulation for venting. The patient's postoperative course was
      uneventful. This method appears to be an alternative approach for aortic valve
      replacement in patients that are not suitable candidates for median sternotomy.

PMID- 18616100
TI  - [A method for determining an appropriate length of gastroepiploic artery graft in
      off-pump coronary artery bypass grafting].
AB  - The gastroepiploic artery (GEA) is available as a graft to the right coronary
      artery (RCA). However, it is hard to determine an optimal anastomotic site and
      GEA graft length after upsetting the heart in off-pump coronary artery bypass
      grafting (OPCAB). To solve these problems, we traced a target coronary tree on
      the diaphragm and marked an optimal anastomotic site by skin markers. A small
      incision was made on the diaphragm at the proximal site of the optimal
      anastomotic position. Appropriate length of GEA graft was determined according to
      the schema on the diaphragm. By postoperative coronary angiogram performed in 22
      cases (25 anastomoses), 22 anastomoses proved patent (88.0%). Flow competition of
      GEA-4 posterior descending artery (PD) was observed in 2 anastomoses (8.0%).
      Occlusion of 4PD-4 atrioventricular node artery (AV) sequential portion was
      observed in 1 anastomosis (4.0%). There was no angulated, redundant or tense
      graft in any of the patent grafts. This method was suggested to be useful in
      determining an optimal anastomotic site and GEA graft length.

PMID- 18616101
TI  - [Complete thoracoscopic lobectomy with systematic nodal dissection via 5 ports
      for lung cancer].
AB  - We herein report a procedure for thoracoscopic lobectomy with mediastinal
      dissection for primary lung cancer using 5 access ports. A thoracoscope is
      inserted through an access port on the mid-axillary line in the 6th intercostal
      space. The availability of 4 instruments through 4 ports makes it easy to divide
      bronchus and pulmonary vessels and to dissect mediastinal lymph nodes. Between
      April 2005 and March 2007, 88 patients with clinical stage I/II primary lung
      cancer underwent this thoracoscopic procedure. Mean (+/- SD) operation time was
      148 +/- 42 minutes and mean (+/- SD) blood loss was 166 +/- 148 ml. No local
      recurrence was found in patients with pathologic stage I/II diseases, whereas
      ipsilateral mediastinal lymphadenopathy occurred in 2 with pathologic stage III A
      disease during the mean post-opetrative period of 518 +/- 200 days. The
      thoracoscopic surgery for lung cancer presented here was seen to be a feasible
      procedure and has the advantage of reducing operative time.

PMID- 18616102
TI  - [Pleural covering method of polyglycolic acid felt with sodium alginate water
      solution for prevention of postoperative pulmonary fistula].
AB  - Sodium alginate is the main ingredient of the seaweed, and its water solution has
      moderate viscosity. The areas of the pleural defect and around the suture line
      were covered with polyglycolic acid felt by using 5% sodium alginate water
      solution in 41 patients who underwent pulmonary resection from November 2006 to
      April 2007. 28 patients were lung cancer, 6 patients were pulmonary metastasis,
      and 7 patients were pneumothorax. The duration of the postoperative air leakage
      was 0.7 days on average. Neither side effect nor complication was observed. This
      method is cheap, safe, and effective for prevention for postoperative pulmonary
      fistula.

PMID- 18616103
TI  - [Efficacy of antero-lateral thoracotomy with partial sternotomy for type B aortic
      dissection after ascending aortic replacement].
AB  - The patient was a 41-year-old man. He had undergone ascending aortic replacement
      due to type A acute aortic dissection 3 years before. He was diagnosed with de
      novo type B aortic dissection, and therefore given conservative treatment.
      Extension of the false lumen was detected in the discending aorta (56 mm in
      diameter). Computed tomography (CT) showed that discending aortic dissection had
      4 lumens and their entries were not clear. Under selective cerebral
      extracorporeal circulation, we performed ascending-arch-descending aortic
      replacement using antero-lateral thoracotomy with partial sternotomy (ALPS
      method). He was discharged on the postoperative day 16. In conclusion, ALPS
      method guarantees wider surgical field and is useful for diffuse thoracic aortic
      disease, especially for aortic dissection with obscure entry which needs broad
      aortic replacement.

PMID- 18616104
TI  - [Emphysematous giant bulla that was difficult to differetiated from
      pneumothorax].
AB  - We experienced 2 patients who admitted to our hospital becaus of acute onset of
      dyspnea and chest pain. Chest X-ray and chest computed tomography showed severe
      atelectasisi of hemilateral lung. After intathoracic drainage under local
      anesthesia, we diagnosed a emphysematous giant bulla. We resected the giant
      bulla.

PMID- 18616105
TI  - [Idiopathic esophageal rupture (Boerhaave syndrome)].
AB  - The idiopathic esophageal rupture, Boerhaave syndrome, is very rare disease.
      Early diagnosis and treatment will produce good clinical course. We experienced a
      case of Boerhaave syndrome with good clinical prognosis because of the prompt
      diagnosis and surgical repair by thoracotomy. A 58-year-old man complained sudden
      chest pain after vomiting. Esophageal rupture was diagnosed by chest computed
      tomography, and the operation was performed after 5 hours from the onset. The
      lesion of the esophageal rupture was on the left side of esophagus just above the
      diaphragm 3 cm in length, which was detected by the combination of thoracoscopy
      and upper gastrointestinal endoscopy. The postoperative clinical course was
      uneventful and he discharged from our hospital 17 days after the thoracotomy.
      Further development of imaging techniques and surgery, such as intraoperative
      endoscopy and thoracoscopy, are useful for the treatment and diagnosis of
      Boerhaave syndrome.

PMID- 18616106
TI  - [Risk management for congenital heart surgery].
AB  - There have been recent improvements in the outcome of congenital heart surgery.
      However, much risk still remains because cardiac surgery itself is not always
      safe and because the postoperative care of children is very complicated. Accurate
      risk evaluation is therefore crucial for effective risk management. This study
      focuses on the database in relation to risk management. A database is essential
      for assessing the risk of each procedure and for providing patients with accurate
      information. Two well-known indices based on the databases of congenital heart
      surgery in the United States and Europe exist for predicting preoperative risk;
      risk adjustment for congenital heart surgery 1 (RACHS 1) and the Aristotle score.
      They offer reliable preoperative assessments of the risks of each procedure, but
      there is still room for improvement. No database for congenital heart surgery
      existed in Japan until this year.

PMID- 18616107
TI  - [Pacemaker implantation in a patient with sick sinus syndrome, complicated with
      persistent left superior vena cava and absent right superior vena cava; report of
      a case].
AB  - A 78-year-old man was referred to our hospital with syncope and palpitation. A
      Holter electrocardiography (ECG) revealed sick sinus syndrome (SSS), and an
      enhanced chest computed tomography (CT) scan showed persistent left superior vena
      cava (PLSVC) and absent right superior vena cava. Myocardial leads and a
      pacemaker implantation were peformed through left anterior thoracotomy approach.
      There were only 10 reports of pacemaker implantation in a patient with SSS
      complicated with PLSVC and absent right superior vena cava in Japan. Open
      thoracotomy approach was thought to be usuful for these patients.

PMID- 18616108
TI  - [Surgical repair of type A aortic dissection with severe atherosclerosis; report
      of a case].
AB  - We report a case of type A aortic dissection with severe atherosclerosis. An 81
      year-old man with acute type A aortic dissection was referred to our hospital.
      Computed tomography revealed DeBakey type II dissection with severe
      atherosclerosis. Ascending aortic replacement was performed urgently, and an
      autologous pericardium strip was placed in the lumen to prevent
      atheroembolization and to reinforce the friable atherosclerotic intima This
      technique was useful for avoiding cerebral vascular accidents. The patient was
      discharged on the 24th operative day with no complications.

PMID- 18616109
TI  - [Pulmonary staple granuloma mimicking lung cancer; report of a case].
AB  - A 67-year-old man was referred to our hospital with chief complaints of bloody
      sputum and an abnormal chest shadow. He had a history of chronic renal failure
      and surgery for right pneumothorax. During dialysis treatment 2 years ago, an
      examination revealed a mass shadow with spiculation in the apex of the right
      lung. Subsequently, he noted bloody sputum, and the shadow became larger. Serum
      Progastrin-releasing-peptide (GRP) levels remained within the range of 70-80
      pg/ml at the previous clinic, but were elevated to 109 pg/ml on admission to our
      hospital. These findings suggested lung cancer developing around the scar due to
      pneumothorax surgery, and we performed an operation. The resected tumor was a
      granuloma formed around a staple with a polytetra-fluoroethylene (PTFE) sheet,
      showing no evidence of malignancy. The patient's postoperative course was
      uneventful, and the serum Pro-GRP level fell to 60 pg/ml.

PMID- 18616110
TI  - [Metastatic lung tumor from uterine leiomyosarcoma; report of a case].
AB  - Endometrial leimyosarcoma is rare neoplasm of all the uterine malignancies. We
      herein present a case of metastatic pulmonary tumor derived from endometrial
      leiomyosarcoma She had undergone hysterectomy for leiomyosarcoma. About 10 years
      after the hysterectomy, metastatic hepatic tumors and peritoneal dissemination
      were pointed out. Following chemotherapy of cisplatin, ifomide and pirarubicine,
      right hepatectomy was performed. About 12 years after the hysterectomy, a
      metastatic lesion appeared in the right lower lung field and right S6
      segmentectomy was performed. About 15 months after the pulmonary resection,
      another metastatic lesion appeared in the remaining right lower lobe. The mass
      grew so rapidly with involvement to adjacent organs that pericardial resection
      was necessary with completion right lower lobectomy. Postoperative chemotherapy
      was performed with the same regimen as previously performed. About 10 months
      after the second pulmonary resection, she died due to dissemination in the right
      haemithorax and malignant pericardial effusion. Careful follow up after the
      surgery for the uterine leiomyosarcoma is recommended because metastatic
      leiomyosarcoma possibly appears even after a long interval, and its progress can
      be so intensive that adjuvant chemotherapy is necessary if it can not be treated
      surgically alone.

PMID- 18616111
TI  - [True thymic hyperplasia which was difficult to distinguish from malignancy in
      adult; report of a case].
AB  - We report a case of 45-year-old man with true thymic hyperplasia. Three years
      earlier he had undergone operation for carcinoma of the floor of mouth. He had no
      symptoms but had been pointed out an anterior mediastinal mass on chest computed
      tomography (CT). Chest CT revealed a well defined solid mass in front of the
      ascending aorta. The mass showed sail sign. The size of this mass did not
      increase on a follow-up chest CT. The signal intensity of this mass was slightly
      inhomogeneous on chest magnetic resonance imaging (MRI). No invasion of the
      surround tissues was observed. Since the possibility of thymoma or other
      malignancy, extended thymectomy under median sternotomy was performed. His
      postoperative course was uneventful. Histopathological examination revealed true
      thymic hyperplasia.

PMID- 18616112
TI  - [Small intestine: development, structure, function].

PMID- 18616113
TI  - [Current status of diagnosis of the small intestinal disease].

PMID- 18616114
TI  - [Algorithm for the diagnosis of small intestinal disease].
AB  - This article describes algorithm for the diagnosis of small intestinal disease.
      In case of massive small intestinal bleeding, angiography or double balloon
      endoscopy should be done firstly under the observation of vital sign and general
      condition. On the other hand, we have to select capsule endoscopy as a first-line
      examination in patients with mild or moderate small intestinal bleeding, and
      thereafter, double balloon endoscopy would be done for the decision of the
      diagnosis. If the patients are suspected of having stricture of the small
      intestine, they will initially undergo small intestinal radiography associated
      with or without abdominal ultrasonography and computed tomography. In addition,
      small intestinal radiography will be performed as a first-line examination in
      patients having abdominal symptom or occult blood stool without overt
      gastrointestinal bleeding, and as a subsequent examination, double balloon
      endoscopy and capsule endoscopy may be done.

PMID- 18616115
TI  - [Endoscopic examination for the small bowel--video capsule endoscopy and double
      balloon enteroscopy].
AB  - In 2001, the new endoscopic procedures for small bowel, video capsule endoscopy
      (VCE) and double balloon enteroscopy (DBE), were introduced in clinical routine.
      Those devices were the breakthrough for the imaging examination of small bowel.
      And each device has many different characteristics as the approach into the
      target organ. But the characteristic common to both is the ability having a total
      observation of small bowel with the high rate. The understanding of the small
      bowel disease is being deeper by diagnosis in collaboration with VCE and DBE
      recently. VCE is superior as the first examination for small bowel and DBE is
      useful for detailed examination and endoscopic therapy.

PMID- 18616116
TI  - [X-ray examination of small intestine--conventional enteroclysis and CT
      enterography].
AB  - We gave an outline while showing the image about conventional enteroclysis and CT
      enterography as X-ray examination of small intestine. Recently a double balloon
      enteroscopy and wireless capsule endoscopy have been used as new procedure for
      small intestinal examination. The former is high invasive examination for a
      patient and has a risk of perforation for the patients with intestinal adhesion
      and consequently it is unsuitable as screening examination. And for the latter,
      the stoppage to stenosis locus of a capsule becomes a problem for a patient
      having intestinal stenosis. Therefore, a conventional enteroclysis is still
      necessary at present. On the other hand, CT enterography which is new small
      intestinal examination procedure is attracting attention as the examination of
      low invasiveness except the exposure to radiation and equally taking very short
      time during examination. CT enterography will be it with more and more useful
      examination for the small intestine in a diagnosis of intestinal neoplasia, ileus
      and inflammatory bowel disease such as Crohn's disease in future.

PMID- 18616117
TI  - [Endoscopic therapy using double balloon endoscopy].
AB  - Double balloon endoscopy (DBE) was developed as a new technique for visualization
      and intervention of the entire small intestine. It has been world-widely reported
      that DBE is very useful for not only diagnosis but also endoscopic therapy. In
      this chapter, hemostatic procedure, polypectomy, dilation therapy for benign
      strictures, reduction of intussusception, removal of foreign bodies, and
      therapeutic ERCP in long-limb surgical bypass patients are described
      introductively. Diagnostic DBE is thought to be safe with a low complication
      rate, but it is reported that the complication rate in therapeutic DBE is higher
      than that associated with colonoscopy. The thin wall of the small intestine can
      explain this. Endoscopic therapy in the small intestine should be performed with
      special care to avoid complications such as bleeding and perforation.

PMID- 18616118
TI  - [New therapy in inflammatory bowel disease (infliximab)].
AB  - In inflammatory bowel disease, such as Crohn's disease, certain immunological
      abnormalities are considered as its cause, but the fundamental mechanism remains
      unclear. However, recent researches revealed that inflammatory cytokines and
      adhesion molecules, such as TNFalpha, IL-6, IL-12 and alpha4 integrin, play an
      important role in the pathogenesis of Crohn's disease. This led to the
      development of anti-cytokine therapy and anti-adhesion molecules therapy using
      monoclonal antibodies to theses cytokines and adhesion molecules. Among them,
      infliximab, a chimeric monoclonal antibody to TNFalpha, is most clinically
      applied and marked therapeutic effect is seen in Crohn's disease. Moreover
      various anti-cytokine therapy was introduced in clinical fields.

PMID- 18616119
TI  - [Primary small intestinal malignant tumors].
AB  - Small intestinal primary adenocarcinomas, carcinoids, gastrointestinal stromal
      tumors (GISTs) were cleared up inadequately because it was hard to examine for
      small intestine by modalities in the 20th century. Obscure gastrointestinal
      bleeding (OGIB) is often caused by these tumors. In future, these tumors will be
      more diagnosed in patients with OGIB by new modalities such as capsule endoscopy
      and double balloon endoscopy. We attempt to present these small intestinal
      malignant tumors using by capsule endoscopy and double balloon endoscopy.

PMID- 18616120
TI  - [Malignant lymphoma of the small intestine].
AB  - The clinicopathologic features of malignant lymphoma of the small intestine were
      reviewed. Genetically, characteristic chromosomal translocations have been
      identified in several B-cell lymphomas, such as t (11 ; 18)/API2-MALT1 in MALT
      lymphoma, t (14 ; 18)/IGH-BCL2 in follicular lymphoma, or t (3 ; 14)/BCL6-IGH in
      diffuse large B-cell lymphoma (DLBCL). Histologically, DLBCL is most frequently
      observed, and T-cell lymphoma and follicular lymphoma are more frequent in small
      intestinal cases than in gastric cases. Macroscopically, small intestinal
      lymphomas are classified as polypoid, ulcerative (including stricturing, non
      stricturing and aneurysmal forms on radiography), multiple lymphomatous
      polyposis, diffuse, or other types. A significant correlation is observed between
      these macroscopic/radiographic and histologic types. The therapeutic strategy,
      such as surgery, chemotherapy, antibiotics or watch-and-wait, should be
      determined based on the disease extent, histologic type, and clinical stage.

PMID- 18616121
TI  - [Diagnosis and treatment for benign small bowel tumor].
AB  - Even if small bowel tumors are benign, they need to be treated when they cause
      symptoms, such as gastrointestinal bleeding or enteric intussusception. It became
      possible to perform endoscopic treatment for small bowel lesions using DBE.
      Therefore for preventing surgical operation, it became important to detect small
      bowel tumors while endoscopic treatment is possible. CE has potential to survey
      small bowel tumors, especially in patients with polyposis.

PMID- 18616122
TI  - [Diagnosis and treatment of Crohn's disease and intestinal tuberculosis].
AB  - Both Crohn's disease and intestinal tuberculosis often have small bowel lesions.
      Morphological findings are very important for correct diagnosis of these disease.
      In this manuscript, we described their characteristics of morphological findings
      including new modality. And as for the treatment of Crohn's disease, we mainly
      mentioned about new medical treatments such as anti-TNFalpha antibody.

PMID- 18616123
TI  - [Nonsteroidal anti-inflammatory drug-induced enteropathy and chronic nonspecific
      multiple ulcers of the small intestine].
AB  - With the development of double balloon endoscopy and video-capsule endoscopy, it
      has become inevitable for gastroenterologist to diagnose small intestinal ulcers
      accurately. Chronic nonspecific multiple ulcers of the small intestine (CNSU) and
      nonsteroidal antiinflammatory drugs-induced enteropathy (NSAIDs-enteropathy)
      share common clinicopathologic features characterized by histologically
      nonspecific ulcers and persistent blood loss. In addition, the two disorders had
      common enteroscopic findings, namely, circular ulcers and concentric stenoses.
      However, CNSU is distinctive of NSAIDs-enteropathy with respect to intractable
      ulcers of various configurations. In consideration of widespread use of NSAIDs, a
      strategy for the prevention of NSAIDs-enteropathy should be examined. Also, much
      more cases of CNSU should be analyzed to establish the pathophysiology of the
      disease.

PMID- 18616124
TI  - [Ischemic enteritis].
AB  - Ischemic enteritis is a rare disease, but its mortality is high, whether it is
      caused by anatomic occlusion of the mesenteric macrovasculature or
      pathophysiologic vasospasm at the microvascular level. Despite advances in the
      management of the critical ill patient, a large proportion of the patients
      recognized with this diagnosis succumb acutely to their condition. Lesser degrees
      of mesenteric ischemia (particularly, in small intestine), even when not manifest
      overtly as the classic clinical syndrome, may contribute to the development of
      systemic sepsis and the multiple organ failure syndrome, which leads to death.
      Therefore, the understanding, recognition, and proper management of mesenteric
      vascular insufficiency has become very important.

PMID- 18616125
TI  - [Vascular lesions of the small intestine].
AB  - Small-intestinal vascular lesions accounted for the bleeding source in a large
      percentage of the patients with mid-GI-bleeding. The progress of enteroscopy has
      been changing the diagnostic and therapeutic algorithm for them. There are 3
      pathological conditions of vascular lesions. Angioectasia is characterized by
      venous/capillary lesions, Dieulafoy' s lesion is characterized by arterial
      lesions, and AVM is a condition in which arteries and veins are directly
      connected without capillary beds. We classified vascular lesions with
      consideration of the presence or absence of pulsatility. The presence or absence
      of arterial components provides important information in understanding the
      pathological conditions. This classification will be useful for selecting
      hemostatic procedure and outcome studies.

PMID- 18616126
TI  - [Meckel's diverticulum and duplication of the alimentary tract].
AB  - Meckel's diverticulum and duplication of the alimentary tract are very important
      as the congenital anomalies of ileum. As these two diseases have the common
      clinical characteristics such as sex, age, symptoms and complications, it is
      often difficult to diagnose before surgery. This report describes and compared
      the clinical aspects of Meckel's diverticulum and duplication of the alimentary
      tract, which were experienced at Nagoya University Hospital and Kariya Toyota
      General Hospital.

PMID- 18616127
TI  - [Gastrointestinal manifestations in Henoch-Schonlein purpura].
AB  - Henoch-Schonlein purpura (HSP) is a systemic, generalized vasculitis.
      Gastrointestinal (GI) symptoms occur in about 80% of patients. GI symptoms
      precede other manifestations in 14% of patients. Delay of diagnosis may lead to
      severe problems such as intestinal perforation. Therefore we need to know the
      characteristics of HSP in case of GI involvement. Although the second part of
      duodenum has been reported to be affected predominantly, our data demonstrate
      that total sites of small intestine are affected and the endoscopic findings of
      small intestine do not differ from other GI tract. Double balloon endoscopy (DBE)
      and capsule endoscopy (CE) have enabled to observe total sites of small
      intestine. We expect that DBE and CE will elucidate the endoscopic
      characteristics of GI tract in HSP in the future.

PMID- 18616128
TI  - [Enteric muco-submucosal elongated polyp].
AB  - The exist of long and slender polypoid lesion like colonic muco-submucosal
      elongated polyp (CMSEP) in gastrointestinal tract except colon is rare. We
      experienced a case of enteric muco-submucosal elongated polyp (EMSEP) in jejunum.
      After the judgment that EMSEP was bleeding source, we performed endoscopic
      polypectomy with double balloon enteroscopy (DBE). Histological findings of
      resected specimen were almost compatible for the feature of CMSEP. According to
      the development of enteroscopy, the chance of detection for EMSEP should be
      increased. The further investigation of CMSEP and EMSEP is necessary for their
      similarity and differences.

PMID- 18616129
TI  - [A newly-developed capsule endoscope in Japan].
AB  - A new video capsule endoscope (VCE) developed by Olympus Medical Systems provides
      upgrade resolution, depth of the field, and brightness of the image, by improving
      the optical system, contained with the new function to adjust the level of
      lighting automatically coordinate with the brightness around, and the original
      handy displayed real-time viewer. Clinical trial using this capsule demonstrated
      the significantly higher diagnostic yield compared with barium contrast
      radiography of small bowel, especially for vascular involvement. Real-time viewer
      could be useful for detecting the gastric transit abnormality as well as for
      increasing the likelihood of a complete small-bowel examination with
      metoclopramide administration. Together with balloon-equipped enteroscopy, VCE is
      a new device which contributes to the diagnosis and the treatment of the small
      bowel lesion.

PMID- 18616130
TI  - [Single-balloon enteroscopy].
AB  - Double-balloon enteroscope (DBE) requires a long preparation time and scope
      insertion is often confused because balloons have to be attached to both the
      endoscope and the overtube. Single-balloon enteroscope (SBE) is a new model
      endoscope produced by Olympus Medical Systems, and SBE does not require a balloon
      to be attached to the scope and has only sliding tube. Therefore, examination,
      preparations and scope insertion are easier than with DBE. SBE provides high
      quality 'Q' type endoscopic images, and narrow-band-imaging can be performed. A
      prototype ultrasonic probe for SBE is now available. We underwent enteroscopy
      with SBE in 40 patients, and the total number of sessions was 50. Total
      enteroscopy was possible in 3 of 5 patients, in whom SBE was inserted deeply
      through both mouth and anus. There were no serious complications. This newly
      developed enteroscopy is useful for the diagnosis and treatment of small
      intestinal bleeding, intestinal stricture and protruding lesions. We believe that
      the single-balloon enteroscope will be more widely used clinically in the near
      future.

PMID- 18616131
TI  - [Diagnosis and pathogenesis in functional dyspepsia].
AB  - Functional gastrointestinal disorders (FGID) such as functional dyspepsia (FD)
      and irritable bowel syndrome are common gastrointestinal diseases in clinical
      practice. FGID is not life-threatened disease, but it is an important disease
      because the patients with FGID have a poor QOL. Recently the Rome criteria for
      the diagnosis of FGID has been established in Western countries, however, whether
      the criteria is suitable for clinical practice in Japan or not has not fully
      discussed. Many factors including gastrointestinal dysmotility, abnormality of
      acid secretion, visceral hypersensitivity, Helicobacter pylori infection or
      stress might play in the pathogenesis of FD. Our previous studies using
      ultrasonography indicate the decrease in gastric emptying and antral motility and
      the increase in duodenogastric reflux in patients with FD. In the treatment of
      FD, prokinetic agents, acid-suppressive drugs and antidepressants have been
      widely used.

PMID- 18616132
TI  - [The efficacy of probiotics in gastrointestinal disease].
AB  - Probiotics are live microbial feed supplement which beneficially affects the host
      animals by improving its microbial balance. Probiotics have been used in the
      treatment of bacterial or viral induced acute intestinal infection. In recent
      years, some clinical studies have shown the therapeutic effects of probiotics in
      the treatment of chronic inflammatory bowel disease (IBD) or prevention of
      allergic disease. Evidence exists for therapeutic use of probiotics in acute
      infectious diarrhea, Clostridium difficile colitis and antibiotic-associated
      diarrhea. Their exact role in IBD, irritable bowel syndrome and prevention of
      cancer has not to be determined. This review summarized the data about probiotics
      in gastrointestinal diseases and examine the mechanisms of action related to
      their therapeutic effects.

PMID- 18616133
TI  - [Generation of artificial lymph nodes (aLNs) and their immunological function].
AB  - We demonstrated that artificial lymph nodes (aLNs) could be generated by the
      transplantation of stromal cell-embedded biocompatible scaffolds into the renal
      subcapsular space in mice. T and B cell domains that form in the aLNs have a
      similar function in the immune response as the follicles of normal lymphoid
      tissue. The aLNs were transplantable to naive normal as well as to severe
      combined immunodeficient (SCID) or RAG deficient mice where aLNs efficiently
      induced secondary immune responses. Antigen-specific secondary responses were
      strongly induced in aLNs even four weeks after their transplantation. The antigen
      specific antibody responses in the lymphocyte-deficient SCID or RAG KO mice
      carrying aLNs were enormous, reaching 7-8mg/mL in serum. The cells from the aLNs
      migrated to the SCID or RAG KO mouse spleen and bone marrow where they expanded
      to generate large numbers of antigen-specific IgG-class antibody-forming cells.
      Secondary responses were maintained with time after antigen challenge, indicating
      that aLNs can support memory B cells and long lived plasma cells. To our
      surprise, memory type CD4+ T cells (CD44(hi), CD62L(lo)) were highly enriched in
      the aLNs as well as in spleens of SCID mice carrying the aLNs. These data
      indicate that the lymph node-like lymphoid tissues which were generated on
      stromal cell-embedded biocompatible scaffolds were easily transplantable and
      could mount a strong antigen specific humoral as well as cellular immune
      responses.

PMID- 18616134
TI  - [Latest overview of type 1 diabetes mellitus].
AB  - Type 1 diabetes mellitus (T1DM) was defined as a heterogeneous disorder
      characterized by severe beta-cell loss. The subtype 1A is characterized by
      abnormal autoimmue-mediated response and 1B is idiopathic etiology, and most of
      patients with T1DM are classified in 1A. There are three subtypes characterized
      by onset, fulminant, acute onset and slowly progressive in T1DM. Among these
      three subtypes, there are differences in genetic etiology, pathogenesis and
      prevalence of autoantibodies. Glutamic acid decarboxylase-65 (GAD65), insulinoma
      associated antigen-2 (IA-2) and insulin are major autoantigens in T1DM and
      autoantibodies for former two are frequently used for clinical diagnosis. Also
      novel autoantibodies for T1DM have been found and clinical characteristics of the
      patients with each antibody will be made clearer. There have been eager efforts
      to develop immunotherapies to prevent islet destruction and to cure the disorder
      with islet transplantation, and new treatment with inhaled insulin regimen.
      Continuous glucose monitoring system(CGMS) has been established to make clearer
      the daily profile of blood glucose of the patients and to improve the metabolic
      control. Most efficient treatment for T1DM is a still insulin injection. However,
      the development of new medical devices and novel treatment rather than insulin
      injection has been done and the progression will promise improved prognosis of
      vascular complications.

PMID- 18616135
TI  - [Health check up and health care advice with a particular focus on the metabolic
      syndrome--background and overview].
AB  - Along with the socio-economic development, the Japanese disease structure has
      changed form the acute diseases dominant to the lifestyle-related chronic
      diseases dominant pattern. Lifestyle-related diseases are defined as the group of
      diseases in which such lifestyle as the habits of eating, exercise, rest, smoking
      and drinking contribute to their outbreak and development. Today the lifestyle
      related diseases account for two third of death, one third of health expenditures
      in Japan. According to the Health Care Reform 2006, health check up and health
      care advice with a particular focus on the Metabolic syndrome will be introduced
      from April, 2008. All citizens between 40 and 74 years old have to participate to
      this program. In this article, the author explains the background and overview of
      this new program.

PMID- 18616136
TI  - [Is this national project effective to keep and promote our health?].

PMID- 18616137
TI  - [Significance of standardizing electronic data in the national program for health
      checkups and guidance].
AB  - The government has started the new national program for health checkups and
      guidance. The author developed the standard electronic format based on HL7CDA-R2.
      2 and XML for the electronic transfer from health checkups institutions and
      guidance institutions to the health insurers. In this format, items to be
      reported and the item codes, unique number for institutions, and the
      specification for describing results of checkups are defined in detail. This is
      the first nationwide standard health-document-exchange based on HL7CDA-R2 and the
      estimated number of participants is between 10 million and 50 million citizens.

PMID- 18616138
TI  - [AGML due to stressor and acid secretion].
AB  - AGML is produced by various causes. Major causes are stressor and drugs, for
      example, NSAIDs. However, it contains various causes: hypovolemic shock, burning,
      and accident of central nervous system. In this chapter, pathological conditions
      of AGML, especially, acid secretion and defence mechanism are discussed.

PMID- 18616139
TI  - [Expanding role of the nucleocytoplasmic transport system during mitosis revealed
      by analyzing the mechanism to load Kid onto mitotic chromosomes].

PMID- 18616140
TI  - ["Flexible" stem cell-niche system in mouse spermatogenesis].

PMID- 18616141
TI  - [Genome of a green alga, Chlamydomonas reinhardtii, lights up key functions of
      plant and animal cells].

PMID- 18616142
TI  - [Identification of novel nuclear innate immune factor Akirin].

PMID- 18616143
TI  - [Molecular basis for peptide-bond formation by aminoacyl-tRNA protein
      transferase].

PMID- 18616144
TI  - [Sex determination in the teleost medaka, Oryzias latipes].

PMID- 18616145
TI  - [Recent progress in flower color modification by biotechnology].

PMID- 18616146
TI  - [Molecular mechanisms of boron transport in plants and its modification for plant
      growth improvement].

PMID- 18616147
TI  - [Photosynthesis and light environment].

PMID- 18616148
TI  - [On the release of a full text search service of PNE back issues].

PMID- 18616149
TI  - [Chronic dizziness in elderly people: its clinical characteristics and magneto
      encephalographic findings].
AB  - Many elderly people complain dizziness which may continue occasionally for months
      or years. According to epidemiological studies, 25-29% of subjects with more than
      60 years of age have the experience of dizziness. Dizziness occurs most commonly
      during head positional changes or walking. Clinical studies have indicated that
      causes of dizziness are nonspecific and multi-factorial; cerebrovascular
      diseases, cervical spondylosis, depressive state, poor vision, orthostatic
      hypotension, whiplash injury, or low cerebrospinal fluid syndrome may play a role
      in the development of dizziness. Patients with dizziness commonly have
      neck/shoulder pain, insomnia, left-right imbalance of visual acuity, scoliosis,
      white matter lesions on head MRI. Little, however, has yet been known as to how
      these symptoms and radiological findings are related to mechanisms of dizziness.
      During the last several years, we performed cerebral functional studies using
      auditory-evoked magneto-encephalography (MEG) in elderly people with chronic
      dizziness. Two types of functional abnormalities were found in dizziness
      patients. One is a rotational abnormality of MEG signals at the temporal cortex
      (Type A) which can be detected by current arrow mapping analysis. This
      abnormality is similar to that detected by non-evoked MEG in temporal lobe
      epilepsy patients. In patients with Type A abnormality, administration of
      anticonvulsants brought about dramatic improvement of dizziness in association
      with disappearance of rotational abnormalities. The other is abnormal
      prolongation of interhemispheric neural conduction time (INCT) between the left
      and right temporal cortices (Type B) which can be estimated from the difference
      of left and right N100 m peak latencies. The INCT was found to be prolonged
      correlating with the grade of white matter lesions on MRI. The INCT also seems to
      be prolonged by lack of sleep. Patients with Type B abnormality commonly have the
      asymmetry of body, such as left-right imbalance of visual acuity, left-right neck
      pain, or remarkable scoliosis, in association with insomnia and/or depressive
      state. According to the study of Penfield, dizziness or vertigo is manifested by
      stimulation of upper temporal cortex and lower parietal cortex. Mechanisms of
      dizziness can be hypothecated on the basis of MEG findings as follows:
      Presumably, there are head-position recognizing (HPR) centers in the left and
      right cerebral hemispheres. The HPR centers may correspond to the vestibular
      cortex or the combined system of vestibular, visual and somatosensory cortices.
      The HPR centers in two hemispheres are receiving head-position signals from
      vestibular, visual and somatosensory corices and are readjusting the dissociation
      of information which may exist between each other through rapid interhemispheric
      neural conduction. In patients with Type A abnormality, dizziness may be caused
      by abnormal neuronal excitements in left or right HPR center. In patients with
      Type B abnormalities, dizziness may be caused by the combined factors, one the
      abnormal prolongation of INCT between left and right HPR centers and the other
      the large dissociation of head position signals between the left and right HPR
      centers due to the body asymmetry, such as scoliosis or left-right neck pain
      imbalance.

PMID- 18616150
TI  - [Case report of nocardia brain abscess that needs to be distinguished from
      metastatic brain tumor].
AB  - We report a 62-year-old woman presenting with nocardia brain abscess that mimics
      metastatic brain tumor. Six months before admission to our hospital, she
      presented with persistent hemoptysis, and a friable endobronchial mass was
      detected at another hospital. However, a definite diagnosis had not been made,
      and then she presented with hemianopia. Her laboratory analysis results showed
      that she had no immunological abnormalities. T1-weighted magnetic resonance
      images of the brain with Gd-DTPA revealed hyperintensive multiple masses with
      surrounding edema. We suspected this case as metastatic brain tumor of unknown
      origin, and the patient underwent biopsy of the supraclavicular lymph node.
      Histopathology results indicated abscess, and gram staining of material obtained
      from the abscess showed Gram-variable rods, which were determined upon culture as
      acid-fast Gram-positive branching rods and identified as Nocardia asteroides.
      Accordingly, we diagnosed the patient as having nocardia brain abscess, and she
      was treated with an oral antibiotic (TMP-SMX). Four months later, the abscesses
      disappeared. The patient recovered after prolonged TMP-SMX therapy with no
      recurrence in over 9 months.

PMID- 18616151
TI  - [Late-onset leukoencephalopathy without hypertension in a case of young-adult
      onset alopecia and spondylosis: a variant of CARASIL?].
AB  - We report herein a 61-year-old man with diffuse leukoencephalopathy, subcortical
      infarcts and cervical and lumbar spondylosis. Medical history included baldness
      and lumbar spondylosis at young-adult onset. His parents were consanguineous
      (cousin). He had been experiencing severe lumbago since 20-years-old, with hair
      loss starting around the same time. He noticed dysarthria and gait disturbance at
      59-years-old. He was admitted to our hospital at 61-years-old with aggravation of
      gait disturbance. On admission, no abnormalities were evident on physical
      examination except for diffuse baldness. Neurological findings included mild
      dementia, bilateral hyperreflexia, paraparesis, right Babinski's sign, and
      pseudobulbar palsy. Blood pressure was normal. T2-weighted imaging of the brain
      revealed diffuse high-intensity in the periventricular white matter and
      subcortical infarcts in the brainstem and bilateral basal ganglia. Marked lumbar
      deformations were observed on spinal MRI. Clinical features in this case met the
      criteria for cerebral autosomal recessive arteriopathy with subcortical
      infarctions and leukoencephalopathy (CARASIL), apart from late onset of cerebral
      infarction.

PMID- 18616152
TI  - [Case of antiamphiphysin antibody-positive stiff-person syndrome with breast
      cancer diagnosed by FDG-PET].
AB  - We report a case of antiamphiphysin antiboddy-positive stiff-person syndrome
      associated with breast cancer, which was detected only by FDG-PET. A 46-year-old
      woman was admitted to our hospital because of painful muscle cramp and stiffness
      of both legs. Laboratory results were negative for anti-GAD antibody, but highly
      positive for antiamphiphysin antibody (1: 61,440). She had been diagnosed as
      having paraneoplastic stiff-person syndrome. However, mammogram, thoracic CT,
      breast MRI and ultrasonic echography showed no abnormal findings. A whole-body
      fluorodeoxyglucose (FDG) PET was performed, showing an increased uptake in the
      left axillary lymph nodes. Then, the left axillary lymph nodes were resected and
      immunohistochemically diagnosed as breast adenocarcinoma. Treatment of stiff
      person syndrome was initiated with corticosteroids followed by chemotherapy
      against breast cancer, which led to a remarkable improvement of her neurological
      symptoms. If there is possibility of paraneoplastic syndromes like stiff-person
      syndrome, FDG-PET is very useful for detecting the occult carcinoma.

PMID- 18616153
TI  - [Case of primary intraocular central nervous system lymphoma with high
      interleukin 10 level and positive cytology in cerebrospinal fluid].
AB  - A 73-year-old woman was admitted to the surgical department of our hospital for
      endoscopic resection of a colonic polyp. The day after endoscopic resection, she
      became drowsy and dysphasic. Two days later, left hemiparesis and gait difficulty
      developed. The next day, hemiparesis progressed bilaterally and dyspnea developed
      due to upper airway stenosis. The most prominent signs were those of bulbar
      palsy. Blood analysis revealed mild inflammatory responses and hyponatremia. T2
      weighted magnetic resonance imaging showed high-intensity lesions in the swollen
      medulla and cervical spinal cord. Those areas and the meninges of the posterior
      fossa were enhanced by gadolinium. Steroid pulse therapy was administered,
      resulting in rapid recovery of bulbar and paretic symptoms with decreased
      enhanced area. At this point, concentration of cerebrospinal fluid interleukin
      (IL)-10 was markedly elevated at 146 pg/ml (normal,< 5 pg/ml), suggesting
      malignant lymphoma. Cytology of the cerebrospinal fluid was repeatedly examined,
      eventually revealing atypical lymphocytes with hyperlobulated nuclei and clear
      nucleoli. Lymphocytes stained with anti-CD20 antibody. These findings strongly
      suggested a diagnosis of primary intraocular and central nervous system lymphoma.
      In the present case, repeated cytology of cerebrospinal fluid was highly
      important for diagnosis in this case of high IL-10 level in cerebrospinal fluid.

PMID- 18616154
TI  - [Case of Charcot-Marie-Tooth disease type 1A with increased cerebrospinal fluid
      proteins and nerve root hypertrophy].
AB  - We report herein a 54-year-old man who first noticed muscle weakness of the hands
      and legs and hypesthesia of the legs at 20-years-old. Symptoms gradually
      worsened. Charcot-Marie-Tooth disease type 1A (CMT 1A) was diagnosed on the basis
      of a nerve conduction study and PMP22 gene duplication. Increased levels of
      cerebrospinal fluid proteins were identified and cervical and lumbosacral nerve
      root hypertrophy was evident on magnetic resonance imaging (MRI). CMT 1A with
      increased CSF proteins and nerve root hypertrophy was carefully evaluated
      clinically and electrophysiologically to rule out other motor sensory
      neuropathies such as CIDP. Increased levels of CSF proteins in this case might
      have resulted from circulatory disturbance of CSF in hypertrophic nerve roots.

PMID- 18616155
TI  - [Case of juvenile stroke caused by methylenetetrahydrofolate reductase
      deficiency].
AB  - The patient had suffered from left hemiparesis at the age of thirteen months, and
      acute ischemic stroke of unknown etiology had been diagnosed at that time. His
      hemiparesis gradually disappeared and he was discharged two weeks after the onset
      without disability. At the age of 17 years, MRI following minor head trauma
      revealed cerebral infarctions located at the right corona radiata and basal
      ganglia. Laboratory findings showed hyperhomocysteinemia. Genetic study disclosed
      methylenetetrahydrofolate reductase deficiency (MTHFRD) (valine/valine type).
      MTHFRD is not detected by the routine infantile mass screening test for
      congenital amino acid metabolic disease, and should be considered in any patient
      with ischemic stroke at under two years of age.

PMID- 18616156
TI  - [Chronic inflammatory demyelinating polyradiculoneuropathy and hyponatremia in a
      patient with chronic graft versus host disease].
AB  - A 54-year-old woman, who was treated with chemotherapy for acute lymphoblastic
      leukemia, developed dysesthesia in her hands and feet at the age of 50 in 2003.
      The following year she underwent hematopoietic stem cell transplantation. In
      2005, she was diagnosed with chronic graft versus host disease (cGVHD). In
      December 2006, she developed dysesthesia in her face and tongue (onset). 50 days
      after the onset, she had a respiratory infection. 10 days later, she was
      hospitalized for muscle weakness of four extremities and progression of
      dysesthesia. Nerve conduction studies and superficial peroneal nerve biopsy
      revealed demyelination. After high-dose immunoglobulin therapy, her muscle
      strength recovered. Hyponatremia was resolved by restriction of fluid intake and
      administration of NaCl. We suggest immunological mechanisms such as cGVHD may
      cause chronic inflammatory demyelinating polyradiculoneuropathy and hyponatremia.

PMID- 18616157
TI  - [Idiopathic intracranial hypertension without headache detected during a routine
      health check].
AB  - A 47-year-old woman was admitted to our hospital with an optic disc edema
      detected during a routine health check. On admission, she exhibited bilateral
      optic disc edema without headache and no visual disturbance. Her cerebrospinal
      pressure was 440 mmH2O, but we detected no abnormalities in the CSF, blood tests,
      brain MRI or MRV. Therefore, she was diagnosed with idiopathic intracranial
      hypertension (IIH). Treatment with acetazolamide reduced the cerebrospinal
      pressure. We suggest that examination of the optic fundi is sufficient to
      diagnose both IIH without headache and IIH with atypical symptoms.

PMID- 18616158
TI  - [Recent advances in the production of heterologous proteins in filamentous
      fungi].
AB  - Filamentous fungi can secrete large amounts of proteins, glycosylate proteins and
      grow faster than plant, insect or mammalian cells. With the advances in fungal
      molecular genetics, strain improvement, and especially fungal genomics,
      filamentous fungi are developed as microbial cell factories for the production of
      heterologous proteins. This review focuses on recent developments of filamentous
      fungi as production hosts, such as protein quality control mechanisms, the
      secretion pathways, protein modification, strain stability, and most importantly
      the application of functional genomics in protein expression. At the same time,
      the strategies for improving heterologous protein production were also discussed
      in details.

PMID- 18616159
TI  - [Comparison of commercialization of transgenic crops in China and world-wide].
AB  - Currently, transgenic crops create huge economic, social and ecological benefits
      with the development of its commercial production. For China, the speed of
      development and commercialization of transgenic crops is a strategic issue for
      the sustainable agriculture development and the international competitiveness of
      our agricultural products. In this paper, we compared and analyzed the status of
      commercialization of transgenic crops in China and world-wide.

PMID- 18616160
TI  - [Generation of mouse UBE2W antibody and analysis of UBE2W expression in mouse
      tissues].
AB  - Ubiquitin conjugating enzyme functions as the second enzyme required for protein
      ubiquitination and plays an important role in ubiquitin transferring and
      substrate specific recognition. UBE2W, a newly described member of E2 family, was
      formerly reported probably involving in phototransduction or retinal degeneration
      in Drosophila. In this study, we report that murine UBE2W harbors a typical UBC
      domain and is highly conserved in different vertebrate homologues. GST-tagged
      UBE2W was expressed in E. coli BL21 (DE3) and purified with GST affinity
      chromatography. Using this antigen, we generated and further separated rabbit
      polyclonal antibody of UBE2W, of which the activity and specificity were
      confirmed by immunoblotting of transiently expressed myc-UBE2W fusion protein.
      Wide expression of UBE2W was found in brain, muscle, heart, lung, liver, spleen,
      kidney and testis of mouse with the generated antibody, indicating the functional
      importance of this novel protein. Furthermore, the UBE2W highly expression was
      confined to the adult testis and was developmental stage-specific.

PMID- 18616161
TI  - [Expression and activity analysis of catalytic domain of PTP1B].
AB  - The amino acid sequence (1-301aa) coding the human PTP1B catalytic domain
      (PTP1Bc) was obtained from the GenBank. The PTP1Bc gene was constructed by
      overlapping PCR, then was inserted into vector pET-22b(+) and expressed
      efficiently in E. coli BL21(DE3) under optimum condition after IPTG induction.
      The proteins were expressed mainly as inclusion bodies with the yield of more
      than 30% of total bacterial proteins. The expressed products were purified
      through Ni(2+)-affinity chromatographic column. After purification, the purity of
      the proteins was more than 95%. Western blotting analysis suggested that the
      purified proteins could specially combine with anti-PTP1B antibody. Enzyme
      activity assay showed that the protein has phosphatase activities.

PMID- 18616162
TI  - [Secretory expression and biological function of IGFBP-3 in eukaryotic cells].
AB  - The cDNA of Insulin-like growth factor binding protein 3 was subcloned into a
      eukaryotic secretory expression vector pSectagA to construct pSectag-IGFBP3.
      Human renal cell carcinoma (RCC) 786-0 cells were transfected with pSectag-IGFBP3
      using lipofectamine 2000. After 48 h, the secretory IGFBP-3 was tested and
      identified by western blotting. Meanwhile, Annexin V-EGFP stain was used to
      analyze the apoptosis of 786-0 cells induced by IGFBP-3. Secretory IGFBP-3
      protein could express successfully in the 786-0 cells and the expressed IGFBP-3
      directly displayed an apoptotic effect on the host cells. This work provides a
      basis for further study on the apoptosis-inducing mechanism of IGFBP-3 and the
      development of a new anti-tumor drug.

PMID- 18616163
TI  - [RAPD genetic analysis on etiological factor of mink self-biting disease].
AB  - Self-biting is a chronic disease, which cause wound to take effect on mink growth
      and pelt quality. In this study, we firstly adopted RAPD (random amplification
      polymorphism DNA) technique based on the reproducible 26 polymorphism primers
      screened from 100 random primers to analyze hereditary constitution of the
      samples from healthy minks and self-biting minks, respectively, at molecular
      level to aim to discuss the causes of self-biting. The results showed that 29
      straps showed polymorphism among amplified 105 straps, of which the polymorphism
      rate is 27.62%. Between healthy and sick mink groups, the amplified DNA fragment
      through different primers indicated different distribution frequency. The
      similarity coefficient of mink groups is 0.8471 and genetic distance (variation)
      index is 0.1529. Through primer S356 (whose sequence is CTGCTTAGGG), we amplified
      different straps between healthy and sick mink. The amplified 1000 bp DNA
      fragment in the sick mink groups can preliminarily serve as molecular genetic
      label to distinguish from healthy and sick mink groups to gradually remove the
      mink individual of self-biting, achieve to purify mink groups and reduce economy
      loss of mink breeding industry. This work provide theoretical basis for further
      study on molecular breeding and disease prevention of mink.

PMID- 18616164
TI  - [Construction of Marek's disease virus serotype 814 strain as an infectious
      bacterial artificial chromosome].
AB  - The aim of this study was to construct the complete genome of Marek's disease
      virus serotype 814 strain as an infectious bacterial artificial chromosome (BAC).
      Using self-designed selection marker Eco-gpt (1.3 kb) and BAC vector pBeloBAC11
      (7.5 kb), we constructed the transfer plasmid pUAB-gpt-BAC11. The plasmid pUAB
      gpt-BAC11 and MDV total-DNA were cotransfected into secondary CEFs; we put the
      virus-containing cells in selection medium for eight rounds and obtained purified
      recombinant viruses. Recombinant viral genomes were extracted and electroporated
      into E. coli, BAC clones were identified by restriction enzyme digestion and PCR
      analysis. Finally, we obtained 38 BAC clones, DNA from various MDV-1 BACs was
      transfected into CEFs, and recombinant virus was reconstituted by transfection of
      MDV-BAC2 DNA. We successfully cloned the complete genome of MDV-1814 strain as an
      infectious bacterial artificial chromosome. With these cloned genomes, a
      revolutionary MDV-DNA engineering platform utilizing RED/ET recombination system
      was constructed successfully, which can help the understanding of MDV gene
      functions and promote the using of MDV as a vector for expressing foreign genes.
      In addition, it opens the possibility to generate novel MDV-1 vaccines based on
      the BACs.

PMID- 18616165
TI  - [Heterologous genes expression on Escherichia coli chromosome lac operon using
      Red recombination].
AB  - To achieve efficient and stable expression of heterologous exogenetic protein or
      antigen in E. coli chromosome, the luciferase report gene was knocked in lacZ
      site of chromosome lac operon by using Red recombination system and selection
      counterselection kan/sacB technology. The quantitative analysis of exogenous gene
      expression indicated that the target gene could be efficiently expressed at lacZ
      site of lac operon. The results confirmed the efficient screening and stable
      expression of heterologous protein or antigen on chromosome by using the
      recombinant engineering technique. This study demonstrated that the chromosome
      could be used as a vector for heterologous protein or antigen and the stable
      expression of exogenous gene on E. coli chromosome had no side effect on the
      bacterial growth and propagation.

PMID- 18616166
TI  - [Rapid detection of Pseudomonas aernginosa by the fluorescence quantitative
      TaqMan PCR assay targetting ETA gene].
AB  - Pseudomonas aernginosa (PA) is one of the most universal pathogens in clinical
      diagnosis, and conventional detection assay has many disadvantages. In this
      research, a pair of specific primers and a TaqMan fluorescent probe were designed
      in the conservative region of ETA gene by the method of bioinformatics analysis,
      the detection method for PA was successfully developed. Different gradient
      concentrations of PA DNA and various pathogen DNA were amplified by fluorescence
      quantitative PCR (FQ-PCR) to confirm the specificity and sensitivity of the
      developed method. Results showed that the developed detection assay is more
      sensible and specific by comparison to the conventional FQ-PCR method, and it is
      valuable for research and application prospects.

PMID- 18616167
TI  - [Analysis of outer membrane proteins of Riemerella antipestifer].
AB  - An isolated virulence Riemerella anatipestifer strain passaged 200 times on TSB
      agar were used for the virulent to avirulent conversion. The effects of passage
      on biological properties of outer membrane proteins (OMPs) were investigated
      using the virulent and avirulent strains. Transmission electron microscopy
      demonstrated that the avirulent strain produced lower amounts of outer membrane
      vesicles and the outer membrane decreased, the cytoplasmic appearance jumbled.
      The OMPs of the virulent strain agglutinated only in RA serotype 2 antisera,
      whereas the OMPs of the avirulent strain agglutinated in antisera of RA 1, 2, 10
      and 11. SDS-PAGE Analysis showed the OMPs profiles of both strains were similar
      but the immunoblotting profiles were different. The protective immunity against
      Riemerella anatipestifer infection was investigated by immunizations with OMPs in
      ducks. ELISA results showed that the OMPs induced the production of antibodies in
      immunized ducks, but the OMPs of virulence strain induced higher antibody titers
      than the attenuated strain (P < 0.05). RA2 group showed significantly higher
      survival rates (100%) than RA200 group (0%) after challenged with the homologous
      virulent strain. The ompA gene of both stains were also amplified by PCR,
      nucleotide homology was 99.9%. In conclusion, OMPs of virulent RA strain are
      suitable candidates for vaccine development. Biological properties of OMPs
      undergoes significant changes during serial passage and suggest that vigilance
      should be used when extrapolating data obtained from the study of high-passage
      strains.

PMID- 18616168
TI  - [Expression, purification and characterization of N-glycanase from
      Schizosaccharomyces pombe in Escherichia coli].
AB  - One pair of primers were designed and synthesized on the base of the cDNA
      sequence encoding Schizosaccharomyces pombe N-glycanase reported on the GenBank.
      The cDNA sequence encoding Peptide N-glycanase was cloned from the
      Schizosaccharomyces pombe by RT-PCR. And then the RT-PCR product was cloned into
      the expression vector pET-15b. The expression vector pET-15b(+)/Png1p was
      transformed into E. coli BL21(DE3). The results showed that the relative
      molecular weight of the enzyme was determined to be approximately 39 kD using SDS
      PAGE. The expression products after induction and purification can catalyze the
      cleavage of N-linked oligosaccharides from glycoprotein coped with heat, but have
      no action on the native glycoprotein with the help of DTT. The percentage of
      deglycosylated RNase B treated with equate Png1p in different reaction
      temperature, pH, concentration of DTT and denatured temperature showed that the
      optimum temperature, the optimum pH is 30 degrees C; the optimum concentration of
      DTT is 10 mmol/L and the optimum denatured temperature is 100 degrees C.

PMID- 18616169
TI  - [Promoter activity of different promoters in recombinant baculovirus-infected Sf9
      cells].
AB  - To compare the activity of different promoter in baculovirus-insect system, a
      series of recombinant baculoviruses were generated harboring the E-GFP reporter
      gene under the control of one of 5 promoters, including the ie1 promoter of
      shrimp white spot syndrome virus (WSSV), the truncated ie1 (mie1) promoter, the
      ETL promoter of the baculovirus, the elongated ETL (mETL) promoter, and the
      polyhedron promoter (P(PH)) of the baculovirus. The expression efficiency of the
      E-GFP reporter gene in the recombinant baculovirus-infected Sf9 cells was
      determined by flow cytometry. The results showed that both ie1 and mETL promoters
      had a strong promoter activity at early phase, while P(PH) showed a strong
      promoter activity at late phase. The ie1 promoter suggested the strongest
      promoter activity. The homologous region 1 (hr1) was also found to enhance the
      ETL promoter activity.

PMID- 18616170
TI  - [Cell lineage tracing of regenerating cells after partial pancreatectomy using
      pseudo-type retrovirus].
AB  - Pancreas is an important mixed gland having both endocrine and exocrine
      functions, and has been proven regeneration after injury. To explore the cell
      lineage tracing methods in pancreas in vivo and the regenerate cells source, we
      used pseudo-type retrovirus to transfect adult mouse pancreas which had been
      partially pancreatectomized by rubbing the kerf using a cotton stick saturated
      with retrovirus suspension then injecting 100 microL retrovirus suspension into
      pancreas, injecting 100 microL retrovirus by caudal vein, or interperitoneally
      injecting retrovirus respectively. The results showed that the method of rubbing
      the kerf then injection of retrovirus suspension into pancreas could more
      effectively mark the pancreatic cells than the caudal vein injection and the
      intraperitoneal injection did in vivo. Furthermore, this study also found that
      some acinus cells could accept injury stimulus signals to regenerate through
      resuming mitosis after pancreatic injury. This study establishes a cell lineage
      tracing method in pancreas in vivo using retrovirus and offers a clue for gene
      therapy of pancreatic diseases using retrovirus vectors.

PMID- 18616171
TI  - [Intravascular biocompatibility of decellularized xenogenic vascular
      scaffolds/PHBHHx hybrid material for cardiovascular tissue engineering].
AB  - Poly (3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHHx) has superior mechanical
      and biocompatibility that may enable it to meet cardiovascular tissue engineering
      applications. We developed hybrid materials based on decellularized xenogenic
      vascular scaffolds that were coated with PHBHHx to investigate the intravascular
      biocompatibility. The hybrid patches were implanted in the rabbit abdominal aorta
      (hybrid patch, n = 12). Only decellularized xenogenic vascular scaffolds were
      implanted without coating as control (uncoated patch, n = 12). The patches were
      explanted and examined histologically, and biochemically at 1, 4 and 12 weeks
      after the surgery. The hybrid patches maintained original shapes, covered by
      confluent layer of cells and had less calcification than uncoated control. The
      results indicated that PHBHHx coating reduced calcification, promoted the
      repopulation of hybrid patch with recipients cells. In conclusion, PHBHHx showed
      remarkable intravascular biocompatibility and would benefit endothelization which
      would be a useful candidate for lumen of cardiovascular tissue engineering.

PMID- 18616172
TI  - [Research on the orientedly immobilized urease via concanavalin A].
AB  - Concanavalin A (ConA) is immobilized on a pre-activated chitosan microspheres,
      and then oriented immobilization of urease is carried out based on the strong
      interaction between ConA and glycoprotein. The optimum immobilization conditions
      are as follows: glutaraldehyde concentration is 3.5%, ConA concentration 1 mg/mL,
      ConA pH 7.0 and urease concentration 0.4 mg/mL. For orientedly immobilized
      urease, the highest activity was allowed at pH 5.0-6.0 and temperature 77 degrees
      C, and the Michaelis constant (Km) was disclosed to be 11.76 mmol/L by Lineweaver
      Burk plot. Compared with the free urease and the randomly immobilized urease, the
      optimum pH of the orientedly immobilized urease becomes smaller and the pH domain
      wider. Orientedly immobilized urease presents higher temperature resistance,
      higher affinity to the substrate, and higher stability of operation.

PMID- 18616173
TI  - [Purification and characterization of a bromoperoxidase from Gracilaria
      lemaneiformis].
AB  - A bromoperoxidase from Gracilaria lemaneiformis was purified to homogeneity using
      a multi-step process of ammonium sulfate precipitation (AS), dialysis, and DEAE
      cellulose 52 anion exchange chromatography. The bromoperoxidase activity was
      unstable or undetectable in crude extract solution. However, it became stable
      with electrophoretic purity after this multiple purification process. The anion
      exchange chromatography purification was a critical step in the purification
      process, which effectively eliminated the phycobiliprotein and smucilaginous
      polysaccharides. The purified bromoperoxidase was a monomeric enzyme with the
      relative molecular masses of 66 kD as determined by denaturing and native
      gradient gel electrophoresis. The optimal pH for bromoination was 6.0 and
      bromoperoxidase activity was stable as stored at a broad pH range of 3.0-9.0. Of
      a range of compounds tested, only vanadium enhanced bromoperoxidase activity.
      Kinetic studies for the bromination of monochlorodimedone (MCD) showed that the
      Km values of Br- and H2O2 are 53.5 micromol/L, 38 micromol/L respectively.

PMID- 18616174
TI  - [Response of bacillus sp. F26 to different reactive oxygen species stress
      characterized by antioxidative enzymes synthesis].
AB  - The oxidative response of Bacillus sp F26 to different forms of reactive oxygen
      species (ROS) stress including H2O2, O2- * and OH * were investigated by using
      diverse generating source of ROS, which were characterized by synthesis of
      antioxidative enzymes. It was shown that the responses of cells to oxidative
      stress are largely dependent on species, mode (instantaneous and continual) and
      intensity of stress. Higher synthesis rate of catalase (CAT) is crucial for
      Bacillus sp F26 to resist H2O2 stress. The damage of H2O2 to cell was minor if
      CAT can efficiently decompose H2O2 entering into cell, furthermore, the response
      can stimulate cell growths and sugar consumption. Conversely, cell growth and
      synthesis of antioxidative enzymes are greatly inhibited when the intensity of
      H2O2 stress overwhelms the cell capability of clearing H2O2. Due to the
      difference in mode and effect on cells between O2- * and H2O2, higher synthesis
      rates of CAT and superoxide dismutase (SOD) couldn't guarantee cells to eliminate
      H2O2 and O2- * efficiently. Therefore, the toxicity to cells induced by
      intracellular O2- * is more severe than H2O2 stress. Unlike response to H2O2 and
      O2- *, OH stress significantly inhibited cell growth and synthesis of
      antioxidative enzymes due to the fact OH * is most active ROS. Our results
      indicated that Bacillus sp F26 will show diverse biological behaviour in response
      to H2O2, O2- * and OH * of stress due to the discrepancy in chemical property. In
      order to survive in oxidative stress, cells will timely adjust their metabolism
      to adapt to new environment including regulating synthesis level of antioxidative
      enzymes, changing rates of cells growth and substrate consumption.

PMID- 18616175
TI  - [High-level production of alkaline polygalacturonate lyase in recombinant Pichia
      pastoris].
AB  - In order to increase the production of alkaline polygalacturonate lyase (PGL) by
      recombinant Pichia pastoris GS115, the effect of cell and methanol concentration
      on the PGL production was carefully investigated by single factor experiment. The
      optimum conditions were listed as follows: the cell concentration 122 g/L, the
      methanol concentration 20 g/L, and the ratio of methanol and cell concentration
      0.16-0.20 g/g (methanol/cell). With the glycerol and methanol feeding strategies,
      the ratio of methanol and cell concentration could be controlled at the range of
      0.171 to 0.195 g/g. And the highest PGL activity (430 u/mL) and highest PGL
      productivity (4.34 u/mL/h) were achieved.

PMID- 18616176
TI  - [Improved efficacy of P277 fused to heat shock protein 65 of Mycobacterium
      tuberculosis against diabetes in nonobese diabetic mice].
AB  - To improve the efficacy of peptide P277 in preventing autoimmune diabetes, heat
      shock protein 65 kD (HSP65) of Mycobacterium tuberculosis var. bovis was fused
      with linear polypeptide epitope of P277 and expressed as soluble protein in
      Escherichia coli. The fusion protein HSP65-P277 was purified by anion exchange
      column chromatography and then used to immunize prediabetic NOD mice with three
      ip inoculations in absence of adjuvants. Serum samples from the immunized mice
      were collected monthly and the concentration of blood glucose was measured. The
      study showed that administration of HSP65-P277 to NOD mice could prevent the
      development of diabetes more efficiently than the peptide P277 itself or HSP65.
      Fused to heat shock protein 65 of Mycobacterium tuberculosis could improve the
      efficacy of diabetes prevention of P277 in nonobese diabetic mice. The results
      suggest the fusion protein of HSP65-P277 would be useful for treating insulin
      dependent diabetes mellitus.

PMID- 18616177
TI  - Microcalorimetric studies of the action on four organic acids in Radix isatidis
      on the growth of microorganisms.
AB  - The actions of four organic acids in Radix isatidis, a traditional Chinese
      medicinal (TCM) herb, on Escherichia coli, Staphylococcus aureus and Shigella
      dysenteriae growth were investigated by microcalorimetry. The four organic acids
      were syringic acid, 2-amino-benzoic acid, salicylic acid and benzoic acid. The
      power-time curves of Escherichia coli, Staphylococcus aureus and Shigella
      dysenteriae growth with and without organic acids were acquired, meanwhile the
      extent and duration of inhibitory effects on the metabolism were evaluated by
      growth rate constants (k1, k2), maximum heat-output[0] power (P(m)) and peak time
      (t(m)). The inhibitory activity varied with different drugs. The sequences of
      anti-microbial activity of the four organic acids on Escherichia coli,
      Staphylococcus aureus and Shigella dysenteriae were all: syringic acid > 2-amino
      benzoic acid > salicylic acid > benzoic acid. And benzoic acid promoted the
      growth of Staphylococcus aureus and Shigella dysenteriae. This study provides a
      basis for the further study on Radix Isatidis.

PMID- 18616178
TI  - [Prediction of outer membrane proteins using support vector machine with combined
      features].
AB  - Outer membrane proteins (OMPs) are embedded in the outer membrane of Gram
      negative bacteria, mitochondria, and chloroplasts. The cellular location and
      functional diversity of OMPs makes them an important protein class. Researches on
      prediction of OMPs by bioinformatics methods can bring helpful methodologies for
      identifying OMPs from genomic sequences and for the successful prediction of
      their secondary and tertiary structures. In this paper, three feature classes
      were calculated from protein sequences: amino acid compositions, dipeptide
      compositions and weighted amino acid index correlation coefficients. Then, three
      feature classes were combined and inputted into a support vector machine (SVM)
      based predictor to identify OMPs from other folding types of proteins. The
      results of discrimination using several combined features including four amino
      acid index categories were calculated, and the influence on discrimination
      accuracy using different correlation coefficients with different orders and
      weights was discussed. In cross-validated tests and independent tests for
      identifying OMPs from a dataset of 1087 proteins belonging to all different types
      of globular and membrane proteins, the method using combined features obtains an
      overall accuracy of 96.96% and 97.33% respectively. And these results outperform
      that of other methods in the literature. Using this method, high specificities
      are shown from the results of identifying OMPs in five bacterial genomes, and
      over 99% OMPs with known three-dimensional structures in the PDB database are
      correctly discriminated. These results indicate that the method is a powerful
      tool for OMPs discrimination in genomes.

PMID- 18616179
TI  - [Predicting RNA secondary structures including pseudoknots by covariance with
      stacking and minimum free energy].
AB  - Prediction of RNA secondary structures including pseudoknots is a difficult topic
      in RNA field. Current predicting methods usually have relatively low accuracy and
      high complexity. Considering that the stacking of adjacent base pairs is a common
      feature of RNA secondary structure, here we present a method for predicting
      pseudoknots based on covariance with stacking and minimum free energy. A new
      score scheme, which combined stacked covariance with free energy, was used to
      assess the evaluation of base pair in our method. Based on this score scheme, we
      utilized an iterative procedure to compute the optimized RNA secondary structure
      with minimum score approximately. In each interaction, helix of high covariance
      and low free energy was selected until the sequences didn't form helix, so two
      crossing helixes which were selected from different iterations could form a
      pseudoknot. We test our method on data sets of ClustalW alignments and structural
      alignments downloaded from RNA databases. Experimental results show that our
      method can correctly predict the major portion of pseudoknots. Our method has
      both higher average sensitivity and specificity than the reference algorithms,
      and performs much better for structural alignments than for ClustalW alignments.
      Finally, we discuss the influence on the performance by the factor of covariance
      weight, and conclude that the best performance is achieved when lambda1 : lambda2
      = 5 : 1.

PMID- 18616180
TI  - [Developmental expression changes of specific genes in adipose tissue for
      different pig breeds by using pathway-focused microarray].
AB  - The expression changes of genes associated with adipose metabolism and regulation
      of cell growth in backfat tissue at five growth stages (1, 2, 3, 4 and 5 months)
      of Landrace (a leaner Western breed) and Taihu pigs (a fatty indigenous Chinese
      breed) were measured by using pathway-focused Oligo microarray. The comparative
      results between two pig breeds of change ratios showed that the fold changes of
      10, 6, 11, 8 and 19 genes were over two times at same month from 1 to 5 months
      respectively. Variance analysis (ANOVA) revealed that 25 genes in Landrace pigs
      showed significantly altered in expression among five growth stages (P < 0.05).
      Principal components analysis (PCA) revealed that angiopoietin-like 4 (ANGPTL4),
      cathepsin K (CTSK), isocitrate dehydrogenase 2(NADP+) (IDH2), lipoprotein lipase
      (LPL), malic enzyme 1 (ME1), stearoyl-CoA desaturase (SCD) and uncoupling protein
      2 (UCP2) displayed distinctive expression patterns from other genes, which
      suggested that these genes may be subject to special regulation during the period
      from 1 to 5 months. K-means clustering analysis revealed that genes in Landrace
      pigs which showed up-regulation were mainly related to the positive regulation of
      fatty acid metabolism and genes in Taihu pigs which showed slight fluctuation
      were mainly related to the regulation of cell growth. Quantitative real-time RT
      PCR was used to verify the microarray data for five modulated genes, and a good
      positive correlation between the two measures of expression was observed for both
      two pig breeds at different growth stages. These results highlight some possible
      candidate genes for porcine carcass and meat quality traits, reveal the
      expressional disciplinarian of correlative genes and provide some data on which
      to base further study of the dynamic balance process for fatty acid biogynthesis
      and hydrolyzation.

PMID- 18616181
TI  - [Expression of Candida antarctica lipase B on yeast surface and synthesis of
      ethyl hexanoate catalyzed by CALB].
AB  - Short-chain esters play a significant role in the food industry as flavor and
      aroma constituents. Candida antarctica lipase B (CALB) is one of the most
      effective catalysts for organic synthesis. We constructed a CALB-displaying yeast
      whole-cell biocatalyst and applied it to esterification from caproic acid and
      ethanol. CALB was fused with the alpha-agglutinin C-terminal and the signal
      peptide of Glucoamylase in pICAS, a yeast surface display vector, to construct
      plasmid pICAS-CALB. An extremely Asn-rich linker, named celAL was inserted in the
      Xho I of pICAS-CALB to construct plasmid pICAS-celAL-CALB. The fused gene was
      under the control of GAPDH promoter. After incubated at 30 degrees C for 96 h the
      lipase hydrolytic activity of the yeast whole cells reached a plateau, 26.26 u/(g
      x dry cell). In nonaqeous media, the yield of 98.0% ethyl hexanoate was obtained
      after 24 h esterification from caproic acid and ethanol (the molar ratio of
      caproic acid : ethanol = 1 : 1.25) using lyophilized CALB displaying yeast whole
      cells.

PMID- 18616182
TI  - [Expression of PPDK from Microbispora rosea subsp. aerata in Escherichia coli and
      its application in pyrosequencing].
AB  - Pyruvate phosphate dikinase (PPDK; EC 2.7.9.1) is found in certain microorganisms
      and plants, and catalyzes the conversion of AMP, PPi and phosphoenolpyruvate
      (PEP) to ATP, Pi and pyruvate. Using the genomic DNA of Microbispora rosea subsp.
      aerata as the template, a DNA fragment encoding the gene PPDK was amplified by
      PCR and inserted into the expression vector pET28a(+), yielding pET28a (+)-PPDK.
      The E. coli BL21 (DE3) was transformed with the pET28a (+)-PPDK. After inducing
      with IPTG, the E. coli BL21 (DE3) [pET28a (+)-PPDK] expressed recombinant PPDK
      fused to an N-terminal sequence of 6-His Tag. The molecular weight of PPDK was
      estimated to be 101 kD by SDS-PAGE. The PPDK was purified by His * Bind Resin
      affinity chromatography and ultrafiltration using 10 kD cut-off membrane. The
      successful application of PPDK in pyrosequencing was also demonstrated.

PMID- 18616184
TI  - [Construction and immunogenicity analysis of antigenic epitopes of swine
      influenza virus].
AB  - Several antigen epitopes were designed according to the sequences of Swine
      influenza virus hemagglutinin (HA) genes and lined with the interval. The gene
      was amplified by PCR and sub cloned into pET30a (+) vector. The fusion protein
      was expressed in E. coli BL21 (DE3) by induced with IPTG and purified by affinity
      chromatography. The molecular weight of the protein was about 20 kD in SDS-PAGE.
      Immunological activity of the fusion protein was analyzed by Western blot. The
      results showed that the fusion protein could interact with anti-His antibody and
      the rabbit antiserum against SIV. The immunized mouse can produced antibodies
      against the target peptide and HI antibody against SIV H1N1 or H3N2. This study
      provides a new vaccine candidate for SIV.

PMID- 18616185
TI  - [A modified TAIL-PCR and its application in isolating gene promoter of wheat].
AB  - Using a modified TAIL-PCR technique, the 5' -flanking region of the X gene in
      wheat was successfully isolated. Two novel modifications of the TAIL-PCR were
      introduced here: using a battery of random 10-mers as the short arbitrary primers
      instead of three degenerate 16-mers; using 29 degrees C instead of 44 degrees C
      as the annealing temperature for the low-stringency cycle; increasing five high
      stringency cycles and reducing five low-stringency cycles; and using single
      primers for the third round of product identification. Isolated 5' -flanking
      region was fused to the GUS gene, and tested for expression in Arabidopsis
      plants. Histochemical analysis of the transgenic plants showed the report gene
      was driven by isolated 5'-flanking region. Modified TAIL-PCR technique could
      isolate rapidly the promoter of any gene from organisms with large genomes.

PMID- 18616183
TI  - [Yeast surface display of HIV-1 gp41 and expression enhancement].
AB  - HIV-1 gp41 has been successfully anchored on the cell surface of yeast
      Saccharomyces cerevisiae by yeast cell-surface display systems using His-tag for
      the detection of protein expression. Gp41 activity has been detected by gp41
      monoclonal antibody. The vector for gp41 yeast display has been constructed as
      follows: the gene-encoding gp41 was amplified by PCR using pMD18T-gp41 as a
      template, and then inserted into shuttle vector pICAS-His by restriction enzyme
      digestion. Next, the vectors were introduced into Saccharomyces cerevisiae MT8-1.
      After cultivation, recombinant cells were immunofluorescence labelled. The bright
      green cells were observed by the microscopy indicating the proteins have been
      displayed on the cell surface successfully, flow cytometry convinced that gp41
      has been folded correctly on the cell surface. Then different concentrations of
      initial glucose were used to enhance the expression of protein. gp41 has been
      expressed by 82.46% yeast cells as the concentration of glucose was 1%. Protein
      expression was depressed when the concentration was increased.

PMID- 18616186
TI  - [Establishment and evaluation of brain adenosine A2A receptors inactivation model
      of mice].
AB  - To establish a model of inactivation adenosine A2A receptors in brain tissues of
      mice, we transplanted bone marrow cells (BMCs) from wild type (WT) C57BL/6 mice
      into A2A receptor knockout (A2A KO) C57BL/6 mice which were previously
      fractionated total body irradiation of 6.2 Gyx2. Six weeks later, we identified
      and evaluated the model. The results showed that the sexual chromagene pattern on
      white blood cells of recipient mice changed from female pattern to male pattern
      and there were 95.9% of A2AR+ cells in peripheral white blood cells of recipient
      mice, whereas there was no significant difference of A2AR mRNA level in brains
      between these recipient mice and A2AR KO mice. Furthermore, there was no
      significant difference of breathing frequency, brain water content and level of
      glutamate between the model mice and WT mice. These results indicated that we
      established successfully a mouse model of inactivation adenosine A2A receptors in
      brain tissues. This may provide a new and efficient strategy to study the effect
      of adenosine A2A receptors in disease and injuries of central nervous system.

PMID- 18616187
TI  - Pay attention to radiation doses.

PMID- 18616188
TI  - Radiology.

PMID- 18616189
TI  - A 3-year-old girl with intermittent fever and abdominal pain.

PMID- 18616190
TI  - A 3-month-old infant with gingival hypertrophy and hepatosplenomegaly.
      Osteopetrosis.

PMID- 18616191
TI  - Radiation protection and safety in pediatric imaging.

PMID- 18616192
TI  - Fetal magnetic resonance imaging: the basics.

PMID- 18616193
TI  - Advances in magnetic resonance imaging of the injured neonatal brain.

PMID- 18616194
TI  - Positron emission tomography/computed tomography (PET/CT) in children.
AB  - Although PET imaging has been available for more than two decades, its use has
      greatly increased lately due to the advent of PET/CT, readily available sources
      of commercially supplied FDG, and mobile scanners. These features have enabled
      PET scanning to expand beyond select major university medical centers, with on
      site cyclotron facilities to smaller institutions including free- standing
      children's hospitals. In these settings, imaging is generally limited to FDG,
      which suffices for most applications, with the majority of studies performed for
      tumor imaging. FDGI is being used for evaluation of many tumors in children, with
      its use in lymphoma being the most established. In lymphoma, it has proven quite
      useful in determining whether active tumor is present in residual masses
      following treatment, which may otherwise contain only residual fibrous tissue.
      For brain tumors, FDGI has some relation to tumor grade, although its more
      important role is distinguishing recurrent or residual tumor from the effects of
      treatment, particularly radiation necrosis. For neurological evaluation,
      interictal FDGI is helpful in localizing potential seizure foci for subsequent
      subdural EEG monitoring. Because of the relatively long uptake time of FDG, true
      ictal studies cannot be performed with FDG, and these remain within the domain of
      SPECT imaging of tracers such as Tc-99m HMPAO. Examinations utilizing
      radiopharmaceuticals other than FDG are significantly more limited in their
      availability and are limited to PET centers with on-site cyclotrons. However,
      these additional agents open the door to many additional studies, including more
      specific tumor-imaging agents of certain tumors such as neuroblastoma. Another
      neurotransmitter, F-18-fluoro-L-dopa, is of benefit outside of the central
      nervous system for evaluating infantile hyperinsulism. The use of PET/CT in
      children is increasing quickly, particularly FDGI imaging of tumors. It is
      expected that over the next few years, its role will become increasingly better
      defined.

PMID- 18616195
TI  - Pediatric vascular anomalies: the role of imaging and interventional radiology.

PMID- 18616196
TI  - Advances in computed tomography.

PMID- 18616197
TI  - Imaging of suspected appendicitis: appropriateness of various imaging modalities.

PMID- 18616198
TI  - An offence to ODPs?

PMID- 18616200
TI  - Evolving perioperative roles: nicety or necessity?
AB  - In recent years we have experienced considerable interest in new roles but since
      the demise of the National Practitioner Programme (England) in 2007, much has
      gone quiet. NHS Education Scotland (NES) continues with the Physician Assistant
      pilots and there is evidence of developments at individual SHA level, but nothing
      like the activity we observed through 2005-2007. However the commitment to secure
      significant service transformation is predicated on the future workforce engaging
      differently and in new ways.

PMID- 18616201
TI  - Surgical site infection, preoperative body washing and hair removal.
AB  - Estimates suggest one in 20 patients develop an infection following surgery,
      costing the NHS around pounds 1bn each year (SSHAIP 2004). This article discusses
      surgical site infections and the commonest bacteria which cause them. It then
      explores two practices, preoperative body washing and preoperative hairremoval,
      and their effect on bacterial reduction and surgical site infection.

PMID- 18616202
TI  - International networking: extending the perioperative potential.
AB  - The theme of last year's Congress was Realising Potential. The road to success is
      always under construction, and there are many choices that we make along the way,
      such as our partner in life, career, or how we spend spare time. A fortuitous
      choice of mine was to get involved with the Education Committee of NATN in 1994,
      as many of my lasting friendships have come as a result of my involvement with
      this organisation. Much of the richness and variety of life comes from the people
      we engage with and the networks which we develop.

PMID- 18616204
TI  - The first ligation of the abdominal aorta.
AB  - To operate on the abdominal aorta is difficult enough today, even with all the
      appurtenances of the modern operating theatre. Yet the first time this was
      performed, as an emergency by Astley Cooper of Guy's Hospital in 1817, it was
      carried out without any form of anaesthetic, in the patient's bed, at night and
      therefore, presumably, by lamp light.

PMID- 18616203
TI  - Errors in medicine administration: how can they be minimised?
AB  - Errors in medicine administration often go unnoticed and unreported. This article
      describes three medicine-related errors and provides recommendations to reduce
      risk. All medicine-related errors should be reported locally and to the National
      Patient Safety Agency (NPSA) so that they can be collated and trends identified.
      Electronic prescribing and patient/medicine identification by bar codes, double
      checking and using colour coded syringes for intravenous and enteral
      administration, employing more clinical pharmacists and regular education may
      reduce medicine-related errors.

PMID- 18616205
TI  - [Oncogeriatrics: essential partner in postgraduate education].

PMID- 18616206
TI  - [New developments in cancer immunotherapy].
AB  - Recent progress unveiling the cellular and molecular basis of the immune response
      allows nowadays the design of novel therapies for tumor immunotherapy. These
      recent approaches translate into response rates that often surpass what can be
      obtained by conventional chemotherapies or targeted therapies. Here we present
      the main current developments with an accent on the Lausanne experience in the
      treatment of melanoma. First, the new developments of peptide-based vaccination
      are presented. Second, approaches related to adoptive transfer are illustrated
      with a particular attention for the patient conditioning using lymphodepletion.
      Finally, the Lausanne project of rational lymphocyte TCR optimization is
      described.

PMID- 18616207
TI  - [Systemic treatment of metastatic colorectal cancer].
AB  - Colorectal cancer is the 2nd cause of cancer related death in industrialised
      countries. 20% of all patients present with metastatic disease at diagnosis and
      need systemic treatment. Since the introduction of irinotecan and oxaliplatin as
      part of standard chemotherapy, and recently the new targeted agents bevacizumab,
      cetuximab and panitumumab, the overall survival for patients suffering from
      metastatic colorectal cancer (mCRC) has increased significantly and nearly
      reaches 2 years nowadays. Surgery or radiofrequency ablation has become central
      in the care of metastatic disease. This article resumes recent therapeutic
      advances in the field and emphasizes the multidisciplinary concertation between
      specialists to obtain the best outcome.

PMID- 18616208
TI  - [Surveillance following curative therapy for breast cancer].
AB  - Surveillance following curative therapy for localised breast cancer has two major
      aims: 1) diagnosis of recurrence or a second tumor: regular interviews and
      physical examinations with a frequency adapted to each case, and yearly
      mammography (+/- ultrasonography), are the only recommended procedure. Additional
      screening is not indicated in asymptomatic patient. 2) Screening for
      complications and side effects due to treatment: tamoxifen treatment should be
      stopped one week prior to any surgery or long trip to avoid thromboembolic
      events, and any metrorrhagia should be investigated due to the risk for
      endometrial cancer. Osteoporosis and arthralgia are frequently observed with
      aromatase inhibitors.

PMID- 18616209
TI  - [Complementary medicine use in oncology patients].
AB  - Through an anonymized questionnaire we assessed the prevalence of complementary
      and alternative medicine (CAM) use in a series of cancer patients treated at the
      Geneva University Hospitals. 152 among the 300 sollicitated patients responded
      and 39 (26.5%) recognized to use CAM, particularly young, and moderate to highly
      educated patients. Patients justify their use of CAM to maximize caring
      ressources, to achieve physical or psychic relief. Most of them recognize to
      share these therapeutic options with their doctor. Satisfaction with traditional
      medicine as well as ignorance of CAM are the main arguments provided by non
      users. The specificity of our hospital context in which results were collected
      and the lack of a common and popular definition of CAM remain the main
      limitations of our enquiry.

PMID- 18616210
TI  - [Acute leukemias].

PMID- 18616211
TI  - [Dr. Google. Google search engine for medicine].

PMID- 18616212
TI  - [The various roles of the physician].

PMID- 18616213
TI  - [The thoughtful questions of Plato].

PMID- 18616214
TI  - [Obesity and inequality, a picture of France today].

PMID- 18616215
TI  - [On the cutting edge of treatment for myopathies].

PMID- 18616216
TI  - [The first public transgenic human embryo in the US].

PMID- 18616217
TI  - [Post Don-Juanism].

PMID- 18616218
TI  - [Synapses].

PMID- 18616219
TI  - Infrared spectra of HC[triple bond]C-MH and M-eta2-(C2H2) from reactions of laser
      ablated group- 4 transition-metal atoms with acetylene.
AB  - Reactions of laser-ablated group 4 transition-metal atoms with acetylene have
      been carried out. The ethynyl metal hydrides (HC[triple bond]C-MH) and
      corresponding pi complexes (M-eta(2)-(C2H2)) are identified in the matrix
      infrared spectra. The observed M-H and C-M stretching absorptions show that
      oxidative C-H insertion readily occurs during codeposition and photolysis
      afterward. The absorptions from the pi complex, on the other hand, are relatively
      weak in the original deposition spectrum but increase dramatically in the process
      of annealing. The vinylidene complex, another plausible product, is not
      identified in this study. The observed spectra and DFT calculations both show
      that the back-donations from the group 4 metals to the antibonding pi* orbital of
      C2H2 are extensive such that the group 4 metals form unusually strong pi
      complexes. Thus, it is the formation of two Ti-C bonds in the group 4 systems
      than leads to the stronger bonding than that in the group 8 systems. While bonds
      form, the Ti atom is weakly bound to C2H2, and we still refer to it as a pi
      complex. Evidence of relativistic effects is also observed in frequency trends
      for the Ti, Zr, and Hf products.

PMID- 18616220
TI  - High-resolution STM imaging of novel single G4-DNA molecules.
AB  - The molecular morphology of long G4-DNA wires made by a novel synthetic method
      was, for the first time, characterized by high-resolution scanning tunneling
      microscopy (STM). The STM images reveal a periodic structure seen as repeating
      "bulbs" along the molecules. These bulbs reflect the helix morphology of the
      wires. The STM measurements were supported by a statistical morphology analysis
      of the DNA pitch length and apparent height relative to the surface. In the
      absence of X-ray and NMR data for these wires, the STM measurements provide a
      unique alternative to characterize the helix morphology.

PMID- 18616221
TI  - Sesquiterpenes from Celastrus vulcanicola as photosynthetic inhibitors.
AB  - Three new sesquiterpenoids (1- 3) with a dihydro-beta-agarofuran skeleton were
      isolated from Celastrus vulcanicola. Their structures were elucidated on the
      basis of spectroscopic analysis, including homonuclear and heteronuclear
      correlation NMR experiments (COSY, ROESY, HSQC, and HMBC), and the absolute
      configurations were determined by circular dichroism and chemical correlations.
      Their effects on photosynthesis were tested. Sesquiterpene 1 (50 microM) inhibits
      both light-dependent synthesis of ATP and the electron flow in chloroplasts,
      whereas at high concentrations the electron flow inhibition was partially
      reversed. Therefore, 1 behaves as a Hill reaction inhibitor and a weak energy
      transfer inhibitor and has two targets of interaction: one located at the oxygen
      evolving complex, and the other located at the light-activated Mg (2+)-ATPase.
      Compound 2 was inactive, whereas 3 acts with the same mechanisms as 1 but was
      less active. Celastrus vulcanicola J. Donnell Smith (Celastraceae) is a
      subtropical woody vine distributed in Central America and the Caribbean. Its
      chemical constituents and biological activity have not yet been investigated.

PMID- 18616223
TI  - X-ray photoelectron emission microscopy and time-of-flight secondary ion mass
      spectrometry analysis of ultrathin fluoropolymer coatings for stent applications.
AB  - Fluoropolymer plasma coatings have been investigated for application as stent
      coatings due to their chemical stability, conformability, and hydrophobic
      properties. The challenge resides in the capacity for these coatings to remain
      adherent, stable, and cohesive after the in vivo stent expansion, which can
      generate local plastic deformation of up to 25%. Plasma-coated samples have been
      prepared by a multistep process on 316L stainless steel substrates, and some
      coated samples were plastically deformed to mimic a stent expansion. Analyses
      were then performed by X-ray photoelectron spectroscopy (XPS), X-ray
      photoelectron emission microscopy (X-PEEM), and time-of-flight secondary ion mass
      spectrometry (TOF-SIMS) to determine the chemical and physical effects of such a
      deformation on both the coating and the interfacial region. While XPS analyses
      always showed a continuous coating with no significant effect of the deformation,
      TOF-SIMS and near-edge X-ray absorption fine structure (derived from X-PEEM) data
      indicated the presence of a certain density of porosity and pinholes in all
      coatings as well as sparse fissures and molecular fragmentation in the deformed
      ones. The smallness of the area fraction affected by the defects and the subtlety
      of the chemical changes could only be evidenced through the higher chemical
      sensitivity of these latter techniques.

PMID- 18616222
TI  - Bio-orthogonal phosphatidylserine conjugates for delivery and imaging
      applications.
AB  - The syntheses of phosphatidylserine (PS) conjugates are described, including
      fluorescent derivatives for potential cellular delivery and bioimaging
      applications. Installation of terminal functional groups (amine, thiol, or
      alkyne) onto the sn-2 chain provides reactive sites for bio-orthogonal
      conjugation of cargo with suitably protected PS derivatives. An amine-containing
      PS forms amide bonds with peptidic cargo, a thiol derivative is designed for
      conjugation to cargo that contain alpha-halo carbonyls or Michael acceptors, and
      the terminal alkyne PS analogue permits "click" conjugation with any azide-tagged
      molecule. This latter conjugation method is quite versatile as it can be
      performed without PS headgroup protection, in aqueous media, and with acid-labile
      cargo.

PMID- 18616224
TI  - Surface stress-charge response of a (111)-textured gold electrode under
      conditions of weak ion adsorption.
AB  - We report a cantilever bending investigation into the variation of surface
      stress, f, with surface charge density, q, for (111)-textured thin films of gold
      in aqueous NaF and HClO 4. The graphs of f(q) are highly linear, and the surface
      stress-charge coefficients, d f/d q, are -1.95 V for 7 mM NaF and -2.0 V for 10
      mM HClO 4 near the potential of zero charge. These values exceed some previously
      published experimental data by a factor of 2, but they agree with recent ab
      initio calculations of the surface stress-charge response of gold in vacuum.

PMID- 18616225
TI  - Separation of CO2 from CH4 using mixed-ligand metal-organic frameworks.
AB  - The adsorption of CO2 and CH4 in a mixed-ligand metal-organic framework (MOF) Zn
      2(NDC) 2(DPNI) [NDC = 2,6-naphthalenedicarboxylate, DPNI = N, N'-di-(4-pyridyl)
      1,4,5,8-naphthalene tetracarboxydiimide] was investigated using volumetric
      adsorption measurements and grand canonical Monte Carlo (GCMC) simulations. The
      MOF was synthesized by two routes: first at 80 degrees C for two days with
      conventional heating, and second at 120 degrees C for 1 h using microwave
      heating. The two as-synthesized samples exhibit very similar powder X-ray
      diffraction patterns, but the evacuated samples show differences in nitrogen
      uptake. From the single-component CO2 and CH4 isotherms, mixture adsorption was
      predicted using the ideal adsorbed solution theory (IAST). The microwave sample
      shows a selectivity of approximately 30 for CO2 over CH4, which is among the
      highest selectivities reported for this separation. The applicability of IAST to
      this system was demonstrated by performing GCMC simulations for both single
      component and mixture adsorption.

PMID- 18616226
TI  - Study of the evaporation of colloidal suspension droplets with the quartz crystal
      microbalance.
AB  - In this Article, we report the application of the quartz crystal microbalance
      (QCM) to study the evaporation of colloidal suspension droplets. Droplets of
      alumina particle suspensions with varying particle size and solid concentration
      have been investigated. Characteristic responses of the resonance frequency of
      the QCM associated with the different evaporation stages have been established.
      Quantitative analysis of the experimental results has been performed by the
      proposed QCM models. An interesting finding is that frequency increase after
      complete drying has been observed in some cases. Interpretation of the frequency
      increase has been developed in terms of the contact stiffness. The possible
      physical mechanisms are also discussed and quantified in terms of various
      interparticle forces.

PMID- 18616227
TI  - Nanostructured ultrathin films of alternating sexithiophenes and
      electropolymerizable polycarbazole precursor layers investigated by
      electrochemical surface plasmon resonance (EC-SPR) spectroscopy.
AB  - Nanostructured ultrathin films of linear and dendrimeric cationic sexithiophenes,
      6TNL and 6TND, respectively, alternated with anionic polycarbazole precursor,
      poly(2-( N-carbazolyl) ethyl methacrylate- co-methacrylic acid) or PCEMMA32, were
      successfully fabricated using the layer-by-layer self-assembly deposition
      technique. The two electro-optically active oligomers exhibited distinct optical
      properties and aggregation behavior in solution and films as studied by UV-vis
      and fluorescence spectroscopy. The stepwise increase of the 6TNL/PCEMMA32 and
      6TND/PCEMMA32 layers was confirmed by UV-vis spectroscopy and in situ surface
      plasmon resonance (SPR) spectroscopy. The intralayer electrochemical
      polymerization and cross-linking behavior of the carbazole functionalized
      PCEMMA32 layers were then investigated using cyclic voltammetry (CV) and
      electrochemical surface plasmon resonance (EC-SPR) spectroscopy. The increase in
      current with each cycle confirmed intralayer cross-linking followed by the doping
      dedoping process within these films. The two types of films differed with respect
      to dielectric constant and thickness changes before and after
      electropolymerization, indicating the influence of the oligothiophene layers.
      This demonstrated for the first time the preparation of highly ordered organic
      semiconductors alternated with in situ electropolymerizable layers in ultrathin
      films.

PMID- 18616228
TI  - Single-step dispersion of functionalities on a silica surface.
AB  - A new process for coating a mesoporous silica gel with a mixture of the grafting
      reagents para-aminophenyltrimethoxysilane and phenyltrimethoxysilane is
      thoroughly analyzed. The dilution of para-aminophenylsilane with phenylsilane at
      different ratios allows the density of the functional amino groups present on the
      silica surface to be controlled, while keeping constant the overall number of
      grafts. Furthermore, the choice of a rigid linker prevents undesirable
      interactions between the active function and the inorganic support that could
      alter the function reactivity. This simple and new method, which results in the
      improvement of the dispersion of a functionality in a one-pot synthesis, could be
      particularly interesting in the field of supported catalysis and molecular
      recognition. The dispersion of the functional groups of the synthesized hybrid
      solids is investigated using a pyrene derivative covalently linked to the free
      amino groups of the para-aminophenylsilanes by analyzing the excimer and monomer
      fluorescence properties of the probe.

PMID- 18616229
TI  - Influence of steric, electric, and dielectric effects on membrane potential.
AB  - The membrane potential arising through nanofiltration membranes separating two
      aqueous solutions of the same electrolyte at identical hydrostatic pressures but
      different concentrations is investigated within the scope of the steric,
      electric, and dielectric exclusion model. The influence of the ion size and the
      so-called dielectric exclusion on the membrane potential arising through both
      neutral and electrically charged membranes is investigated. Dielectric phenomena
      have no influence on the membrane potential through neutral membranes, unlike ion
      size effects which increase the membrane potential value. For charged membranes,
      both steric and dielectric effects increase the membrane potential at a given
      concentration but the diffusion potential (that is the high-concentration limit
      of the membrane potential) is affected only by steric effects. It is therefore
      proposed that membrane potential measurements carried out at high salt
      concentrations could be used to determine the mean pore size of nanofiltration
      membranes. In practical cases, the membrane volume charge density and the
      dielectric constant inside pores depend on the physicochemical properties of both
      the membrane and the surrounding solutions (pH, concentration, and chemical
      nature of ions). It is shown that the Donnan and dielectric exclusions affect the
      membrane potential of charged membranes similarly; namely, a higher salt
      concentration is needed to screen the membrane fixed charge. The membrane volume
      charge density and the pore dielectric constant cannot then be determined
      unambiguously by means of membrane potential experiments, and additional
      independent measurements are in need. It is suggested to carry out rejection rate
      measurements (together with membrane potential measurements).

PMID- 18616230
TI  - Self-assembly of perfunctionalized beta-cyclodextrins on a quartz crystal
      microbalance for real-time chiral recognition.
AB  - This study reports the development of novel chiral sensors based on the self
      assembly of perfunctionalized beta-cyclodextrins (beta-CD) on a quartz crystal
      microbalance transducer for real time chiral recognition. Ten chiral sensors
      immobilized with mercaptyl perfunctionalized beta-cyclodextrins were found to
      exhibit promising enantioselectivity in the gas phase. Well-defined sizes of
      molecular cavities of the modified beta-CDs associated with cooperative weak
      interactions with the host molecules afforded enhanced chiral discrimination.
      This study contributes to the realization of novel chiral sensors applicable for
      real-time recognition and analysis of enantiomeric alcohols and lactates.

PMID- 18616231
TI  - Nonplanarity of adenine: vibrational transition moment angle studies in helium
      nanodroplets.
AB  - Mid-infrared spectra are reported for adenine monomer in helium nanodroplets. We
      show that there is only one tautomer of adenine, the global minimum structure,
      observed in helium nanodroplets and characterized by using ab initio calculations
      and the measurement of vibrational transition moment angles (VTMAs) for the
      various vibrational modes of the adenine monomer. On the basis of the VTMA
      analysis on the amino group of the global minimum tautomer, which gives insights
      into its nonplanarity, a detailed VTMA study of three lowest-energy amino
      tautomers of adenine is discussed in this study.

PMID- 18616232
TI  - Kinetics of metal ion binding by polysaccharide colloids.
AB  - The dynamics of metal sorption by a gel-like polysaccharide is investigated by
      means of the electrochemical technique of stripping chronopotentiometry (SCP).
      The measured response reflects the diffusive flux properties of the metallic
      species in the dispersion. The colloidal ligand studied here is a functionalized
      carboxymethyldextran. Its complexation with Pb(II) reveals a time dependence that
      identifies strong differences in the dynamic nature of the successive metal
      complexes formed. Apparently, the formation of intramolecular bidentate complexes
      requires a slow conformational reorganization of the macromolecule that becomes
      the rate-limiting step in the complexation reaction. The relevant parameters for
      metal binding and release kinetics are computed and thus provide knowledge of the
      time-dependent stability and lability of metal polysaccharide complexes.

PMID- 18616233
TI  - Vibrational spectra of the boron halides and their molecular complexes. Part 11.
      Complexes of boron trifluoride with phosphine and its methyl derivatives. An ab
      initio study.
AB  - Ab initio calculations, at the second-order level of Moller-Plesset perturbation
      theory, using a triple-zeta Gaussian basis set with polarization and diffuse
      functions on all atoms, have been carried out on the donor-acceptor complexes of
      boron trifluoride with phosphine and its mono-, di-, and trimethyl derivatives.
      The structures, interaction energies, and vibrational spectra of the complexes
      were determined. The preferred conformer was found to be the staggered species in
      each case. The computed data were compared with those for some similar complexes
      containing boron trifluoride and a series of related oxygen, sulfur, and nitrogen
      bases, and the effect of successive methyl substitution in each series was
      investigated.

PMID- 18616234
TI  - Excitation energies from spin-restricted ensemble-referenced Kohn-Sham method: a
      state-average approach.
AB  - A time-independent density functional approach to the calculation of excitation
      energies from the ground states of molecules typified by the strong nondynamic
      electron correlation is suggested. The new method is based on the use of the spin
      restricted ensemble-referenced Kohn-Sham formalism [Filatov, M.; Shaik, S. Chem.
      Phys. Lett. 1999, 304, 429] for the calculation of the ground state. In the new
      method, the average energy of the ground state and a state created by a single
      excitation thereof is minimized with respect to the Kohn-Sham orbitals and their
      fractional occupation numbers. The lowest singlet excitation energies obtained
      with the help of the new formalism for a number of model systems, such as the
      hydrogen molecule with stretched bond, twisted ethylene, and twisted hexa-1,3,5
      triene, are compared with the results of the time-dependent density functional
      theory, with the results of ab initio CASSCF/CASPT2 calculations, and with the
      experimental data. Applicability of the new method to the description of
      photochemical reactions is discussed.

PMID- 18616235
TI  - Tetragonal distortion of structural defects in Cr3+ doped in several perovskites
      calculated from the EPR and optical data: a complete energy matrix study.
AB  - This paper describes a novel application of a ligand field model in the study of
      the local molecular structure of the (CrF 6) (3-) coordination complex. Based on
      the ligand field model, the complete energy matrix which contains the electron
      electron repulsion interaction, the ligand field interaction, the spin-orbit
      coupling interaction, and the Zeeman interaction, has been constructed for a d
      (3) configuration ion in a tetragonal ligand field. In order to study the
      relation between the EPR, the optical spectra, and the local lattice structures
      around the centers with tetragonal symmetry in AMF 3 codoped with Cr (3+) and Li
      (+) ions, a three-layer-ligand model is proposed. By diagonalizing the complete
      energy matrix and employing the three-layer-ligand model, the variational ranges
      of the local structural parameters around the Cr (3+) ions are determined,
      respectively. The results show that the local lattice structures around the Cr
      (3+) ions in AMF 3 exhibit a compressed distortion, and the magnitude of
      distorted parameter Delta R 1 of the Cr (3+)-V M center is different from that of
      the Cr (3+)-Li (+) center in AMF 3. The compressed distortion is ascribed to the
      fact that the radius of the Cr (3+) ion is smaller than those of M (2+) (M = Cd,
      Mg, Zn). Moreover, a linear correlation between the difference in the magnitude
      of distortion parameterDelta R for two different defect centers and the
      difference in the corresponding values of the zero-field-splitting parameter
      Delta D are found first.

PMID- 18616236
TI  - Chemical proteomics-based drug design: target and antitarget fishing with a
      catechol-rhodanine privileged scaffold for NAD(P)(H) binding proteins.
AB  - Drugs typically exert their desired and undesired biological effects by virtue of
      binding interactions with protein target(s) and antitarget(s), respectively.
      Strategies are therefore needed to efficiently manipulate and monitor cross
      target binding profiles (e.g., imatinib and isoniazid) as an integrated part of
      the drug design process. Herein we present such a strategy, which reverses the
      target --> lead rational drug design paradigm. Enabling this approach is a
      catechol-rhodanine privileged scaffold for dehydrogenases, which is easily tuned
      for affinity and specificity toward desired targets. This scaffold crosses
      bacterial (E. coli) cell walls, and proteome-wide studies demonstrate it does
      indeed bind to and identify NAD(P)(H)-binding proteins that are potential drug
      targets in Mycobacterium tuberculosis and antitargets (or targets) in human
      liver. This approach to drug discovery addresses key difficulties earlier in the
      process by only pursuing targets for which a chemical lead and optimization
      strategy are available, to permit rapid tuning of target/antitarget binding
      profiles.

PMID- 18616237
TI  - Methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo
      [3',4':1,2]pyridin[3,4-b]indol-2-substituted acetates: synthesis and three
      dimensional quantitative structure-activity relationship investigation as a class
      of novel vasodilators.
AB  - To find selective inhibitor of phosphodiesterase type 5 (PDE5), the essential
      structure elements of clinically used drugs sildenafil, vardenafil, and tadalafil
      were combined and a tetracyclic parent was constructed to which in 2-positions
      substituted acetic acid methylesters were introduced to form 17 novel
      vasodilators, methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H
      imidazo[3',4':1,2]- pyridin[3,4-b]indol-2-substituted acetates. By molecular
      field analysis (MFA), an equation of three-dimensional quantitative structure
      activity relationship (3D QSAR) was established, which not only revealed the
      dependence of the in vitro vasorelaxation activities on the structures but also
      pointed out the way to design new lead compounds properly. Docking these novel
      vasodilators into the hydrophobic pocket of phosphodiesterase type 5 (PDE5)
      revealed that their adaptabilities to this pocket did significantly affect on
      their vasorelaxation activity. Actually, the docking adaptabilities of these
      novel vasodilators to PDE5 were consistent with the conformational requirements
      of them to MFA and with the crystal conformation of two representatives.

PMID- 18616238
TI  - Temperature- and stoichiometry-controlled dimensionality in a magnesium 4,5
      imidazoledicarboxylate system with strong hydrophilic pore surfaces.
AB  - 1D, 2D, and 3D three metal-organic hybrid frameworks of Mg (II) have been
      synthesized using 4,5-imidazoledicarboxylic acid (H 3idc) with control of the
      temperature and stoichiometry in a hydrothermal technique. All of the frameworks
      show high thermal stability, and frameworks 1D and 3D provide highly hydrophilic
      pore surfaces, correlated by the selective sorption of water molecules over the
      organic vapor and other gases like N 2 and CO 2.

PMID- 18616239
TI  - Biphasic hydrogenation over PVP stabilized Rh nanoparticles in hydroxyl
      functionalized ionic liquids.
AB  - Polyvinyl pyrrolidone stabilized rhodium nanoparticles are highly soluble in
      hydroxyl-functionalized ionic liquids, providing an effective and highly stable
      catalytic system. In hydrogenation reactions, excellent results were obtained,
      and transmission electron microscopy, solubility determinations, and leaching
      experiments were employed to quantify the advantages of this catalytic system.

PMID- 18616240
TI  - Europium(III) reduction and speciation within a Wells-Dawson heteropolytungstate.
AB  - The redox speciation of Eu(III) in the 1:1 stoichiometric complex with the alpha
      1 isomer of the Wells-Dawson anion, [alpha-1-P 2W 17O 61] (10-), was studied by
      electrochemical techniques (cyclic voltammetry and bulk electrolysis), in situ
      XAFS (X-ray absorption fine structure) spectroelectrochemistry, NMR spectroscopy
      ( (31)P), and optical luminescence. Solutions of K 7[(H 2O) 4Eu(alpha-1-P 2W 17O
      61)] in a 0.2 M Li 2SO 4 aqueous electrolyte (pH 3.0) show a pronounced
      concentration dependence to the voltammetric response. The fully oxidized anion
      and its reduced forms were probed by Eu L 3-edge XANES (X-ray absorption near
      edge structure) measurements in simultaneous combination with controlled
      potential electrolysis, demonstrating that Eu(III) in the original complex is
      reduced to Eu(II) in conjunction with the reduction of polyoxometalate (POM)
      ligand. After exhaustive reduction, the heteropoly blue species with Eu(II) is
      unstable with respect to cluster isomerization, fragmentation, and recombination
      to form three other Eu-POMs as well as the parent Wells-Dawson anion, alpha-[P 2W
      18O 62] (6-). EXAFS data obtained for the reduced, metastable Eu(II)-POM before
      the onset of Eu(II) autoxidation provides an average Eu-O bond length of 2.55(4)
      A, which is 0.17 A longer than that for the oxidized anion, and consistent with
      the 0.184 A difference between the Eu(II) and Eu(III) ionic radii. The reduction
      of Eu(III) is unusual among POM complexes with Lindqvist and alpha-2 isomers of
      Wells-Dawson anions, that is, [Eu(W 5O 18) 2] (9-) and [Eu(alpha-2-As 2W 17O 61)
      2] (17-), but not to the Preyssler complex anion, [EuP 5W 30O 110] (12-), and
      fundamental studies of materials based on coupling Eu and POM redox properties
      are still needed to address new avenues of research in europium hydrometallurgy,
      separations, and catalysis sciences.

PMID- 18616241
TI  - Ternary rare-earth titanium antimonides RE2Ti(11-x)Sb(14+x) (RE = Sm, Gd, Tb,
      Yb).
AB  - The isostructural rare-earth titanium antimonides RE 2Ti 11 - x Sb 14 + x ( RE =
      Sm, Gd, Tb, Yb) have been synthesized by arc-melting reactions of the elements.
      Single-crystal X-ray diffraction revealed that they adopt a new structure type
      (Pearson symbol oP54, space group Pnma, Z = 2; a = 15.8865(6)-15.9529(9) A, b =
      5.7164(2)-5.7135(3) A, c = 12.9244(5)-12.9442(7) A for RE = Sm-Yb). The structure
      consists of titanium-centered octahedra (CN6) and pentagonal bipyramids (CN7)
      connected to form a 3D framework whose cavities are filled with RE atoms. 1D
      linear skewers of titanium atoms, within face-sharing octahedral chains, and
      similar skewers of antimony atoms, associated with the titanium-centered
      pentagonal bipyramids, extend along the b direction. On proceeding from Sm 2Ti
      11Sb 14 to Tb 2Ti 10.41(1)Sb 14.59(1) and Yb 2Ti 10.58(1)Sb 14.42(1), antimony
      atoms are disordered within some of the titanium sites. Resistivity measurements
      on the samarium and ytterbium members indicated metallic behavior.

PMID- 18616242
TI  - A valence bond modeling of trends in hydrogen abstraction barriers and transition
      states of hydroxylation reactions catalyzed by cytochrome P450 enzymes.
AB  - The paper outlines the fundamental factors that govern the mechanisms of alkane
      hydroxylation by cytochrome P450 and the corresponding barrier heights during the
      hydrogen abstraction and radical rebound steps of the process. This is done by a
      combination of density functional theory calculations for 11 alkanes and valence
      bond (VB) modeling of the results. The energy profiles and transition states for
      the various steps are reconstructed using VB diagrams (Shaik, S. S. J. Am. Chem.
      Soc. 1981, 103, 3692-3701. Shaik, S.; Shurki, A. Angew. Chem. Int. Ed. 1999, 38,
      586-625.) and the DFT barriers are reproduced by the VB model from raw data based
      on C-H bond energies. The model explains a variety of other features of P450
      hydroxylations: (a) the nature of the polar effect during hydrogen abstraction,
      (b) the difference between the activation mechanisms leading to the Fe(IV) vs the
      Fe(III) electromers, (c) the difference between the gas phase and the enzymatic
      reaction, and (d) the dependence of the rebound barrier on the spin state. The VB
      mechanism shows that the active species of the enzyme performs a complex reaction
      that involves multiple bond making and breakage mechanisms by utilizing an
      intermediate VB structure that cuts through the high barrier of the principal
      transformation between reactants and products, thereby mediating the process at a
      low energy cost. The correlations derived in this paper create order and organize
      the data for a process of a complex and important enzyme. This treatment can be
      generalized to the reactivity patterns of nonheme systems and synthetic iron-oxo
      porphyrin reagents.

PMID- 18616244
TI  - Electronic properties of conjugated polyelectrolyte thin films.
AB  - The electronic properties of conjugated polyelectrolytes (CPEs) with
      poly(fluorene-co-phenylene) backbones and different counterions and charges have
      been investigated using absorption and ultraviolet photoelectron spectroscopy
      (UPS). The optical energy band gap of CPEs depends mainly on their conjugated
      backbone and are nearly insensitive to the charges or counterions. UPS
      measurements reveal that electron injection from Au to polymers with cationic
      groups is more efficient than for the neutral and anionic counterparts. The
      vacuum levels of CPEs were also shifted toward higher or lower binding energy,
      relative to that of Au, depending on the charge and counterion presence, and
      provide insight into the general alignment of dipoles at the metal/organic
      interface.

PMID- 18616245
TI  - Enantio- and diastereoselective catalytic alkylation reactions with aziridines.
AB  - The first asymmetric phase transfer catalyzed alkylation reaction of a range of
      carbon acids with N-sulfonyl aziridines is reported. When 10 mol % of a cinchona
      derived quaternary ammonium salt was employed as the catalyst under mildly basic
      conditions, N-o-(trifluoromethane)benzenesulfonyl aziridine was efficiently ring
      opened to afford the amino ethylene products in consistently high yields and high
      enantioselectivities (up to 97% ee). By employing substituted aziridines in
      single enantiomeric form, the corresponding enantiopure alkylation products could
      be obtained with a range of pronucleophiles in high yields and moderate to high
      diastereoselectivities (up to 30:1 dr).

PMID- 18616246
TI  - Carbon-fluorine reductive elimination from a high-valent palladium fluoride.
AB  - We have observed two high-valent arylpalladiumfluoride complexes that afford
      carbon-fluorine bond formation upon thermolysis.

PMID- 18616247
TI  - A heterobimetallic complex with an unsupported uranium(III)-aluminum(I) bond:
      (CpSiMe3)3U-AlCp* (Cp* = C5Me5).
AB  - A heterobimetallic complex with the first unsupported bond between an actinide
      and a group 13 element, (CpSiMe3)3U-AlCp* (Cp* = C5Me5) (1), was synthesized by
      reaction of (CpSiMe3)3U and 1/4(Cp*Al)4 in toluene. Density functional theory
      calculations indicate that the U-Al bond exhibits some covalent character
      resulting from a Cp*Al-->U charge-transfer.

PMID- 18616248
TI  - Cyclic 1,3-dipoles or acyclic phosphonium ylides? Electronic characterization of
      "Montrealones".
AB  - The structural features of a recently introduced class of 1,3-dipolar reagents
      have been computed by density functional theory and ab initio methods. The
      reagents are formally derived from Munchnones by replacement of the C O group
      with a PR3 unit. The parent species (PR3 = PH3) shows a long P...O interaction
      (2.55 A at the B3LYP/6-31+G(d) level), together with a nonplanar ring, and is
      best described as a weakly chelated acylamino-phosphonium ylide. The
      corresponding acyclic form, in which the P...O interaction is absent, is
      predicted to be 2-3 kcal mol-1 higher in enthalpy. Variation of the phosphorus
      substituents exerts a marked effect on the P...O distance, with electron
      withdrawing groups favoring a covalent interaction [P...O 1.97 A for PR3 =
      PPh(catechyl)] and electron-donating groups favoring a weak interaction [P...O
      3.92 A for PR3 = PPh3]. However, this variation has little effect on the relative
      energies of the cyclic and acyclic forms. The barriers for concerted
      cycloadditions with ethylene are 22.8 kcal mol-1 (PH3), 31.7 kcal mol-1 (PPh3),
      and 16.2 kcal mol-1 [PPh(catechyl) with axial O], which correspond with
      experimental observations and follow the same trend as the energies required to
      distort the dipole to the TS geometry.

PMID- 18616249
TI  - Rational design of a minimal size sensor array for metal ion detection.
AB  - The focus of this study was to demonstrate that, in the luminescent sensors, the
      signal transduction may possibly be the most important part in the sensing
      process. Rational design of fluorescent sensor arrays for cations utilizing
      extended conjugated chromophores attached to 8-hydroxyquinoline is reported. All
      of the optical sensors utilized in the arrays comprise the same 8
      hydroxyquinoline (8-HQ) receptor and various conjugated chromophores to yield a
      different response to various metal cations. This is because the conjugated
      chromophores attached to the receptor are partially quenched in their resting
      state, and upon the cation coordination by the 8-HQ, the resulting
      metalloquinolinolate complex displays a change in fluorescence. A delicate
      balance of conjugation, fluorescence enhancement, energy transfer, and a heavy
      metal quenching effect results in a fingerprint-like pattern of responses for
      each sensor-cation complex. Principal component analysis (PCA) and linear
      discriminant analysis (LDA) are used to demonstrate the contribution of
      individual sensors within the array, information that may be used to design
      sensor arrays with the smallest number of sensor elements. This approach allows
      discriminating between 10 cations by as few as two or even one sensor element.
      Examples of arrays comprising various numbers of sensor elements and their
      utility in qualitative identification of Ca(2+), Mg(2+), Cd(2+), Hg(2+), Co(2+),
      Zn(2+), Cu(2+), Ni(2+), Al(3+), and Ga(3+) ions are presented. A two-member array
      was found to identify 11 analytes with 100% accuracy. Also the best two of the
      sensors were tested alone and both were found to be able to discriminate among
      the samples with 99% and 96% accuracy, respectively. To illustrate the utility of
      this approach to a real-world application, identification of enhanced soft drinks
      based on their Ca(2+), Mg(2+), and Zn(2+) cation content was performed. The same
      approach to reducing array elements was used to construct three- and two-member
      arrays capable of identifying these complex analytes with 100% accuracy.

PMID- 18616250
TI  - A platinum supramolecular square as an effective G-quadruplex binder and
      telomerase inhibitor.
AB  - In this contribution, we report that a self-assembled platinum molecular square
      [Pt(en)(4,4'-dipyridyl)]4 can act as an efficient G-quadruplex binder and
      telomerase inhibitor. Molecular modeling studies show that the square arrangement
      of the four bipyridyl ligands, the highly electropositive nature of the overall
      complex, as well as hydrogen bonding interactions between the ethylenediamine
      ligands and phosphates of the DNA backbone all contribute to the observed strong
      binding affinity to the G-quadruplex. Through thermal denaturation studies with
      duplex and quadruplex FRET probes and enzymatic assays, we demonstrate that this
      platinum square strongly binds to G-quadruplexes and can act as an inhibitor of
      telomerase. This study thus shows the potential of supramolecular self-assembly
      to readily generate scaffolds of unique geometries for effective targeting of G
      quadruplexes and for the ultimate development of selective antitumor therapies.

PMID- 18616251
TI  - Energetics of cyclohexene adsorption and reaction on Pt(111) by low-temperature
      microcalorimetry.
AB  - The heat of adsorption and sticking probability of cyclohexene on Pt(111) were
      measured as a function of coverage using single-crystal adsorption calorimetry in
      the temperature range from 100 to 300 K. At 100 K, cyclohexene adsorbs as intact
      di-sigma bonded cyclohexene on Pt(111), and the heat of adsorption is well
      described by a second-order polynomial (130 - 47 theta - 1250 theta(2)) kJ/mol,
      yielding a standard enthalpy of formation of di-sigma bonded cyclohexene on
      Pt(111) at low coverages of -135 kJ/mol and a C-Pt sigma bond strength of 205
      kJ/mol. At 281 K, cyclohexene dehydrogenates upon adsorption, forming adsorbed 2
      cyclohexenyl (c-C6H(9,a)) and adsorbed hydrogen, and the heat of adsorption is
      well described by another second-order polynomial (174 - 700 theta + 761
      theta(2)) kJ/mol. This yields a standard enthalpy of formation of adsorbed 2
      cyclohexenyl on Pt(111) at a low coverage of -143 kJ/mol. At coverages below 0.10
      ML, the sticking probability of cyclohexene on Pt(111) is close to unity (>0.95),
      independent of temperature.

PMID- 18616252
TI  - Insight into the mechanism of the asymmetric ring-opening aminolysis of 4,4
      dimethyl-3,5,8-trioxabicyclo[5.1.0]octane catalyzed by titanium/BINOLate/water
      system: evidence for the Ti(BINOLate)2-bearing active catalyst entities and the
      role of water.
AB  - The mechanism of the enantioselective ring-opening aminolysis of 4,4-dimethyl
      3,5,8-trioxabicyclo[5.1.0]octane with benzylamine, catalyzed by the titanium
      BINOLate species generated in situ from a mixture of enantiopure BINOL (1,1'-bi-2
      naphthol), Ti(OiPr)4, and H2O in the presence of benzylamine in toluene, was
      investigated in detail using a combination of reaction profile measurements,
      nonlinear effect (NLE) studies, solution (1)H NMR analysis, electrospray
      ionization mass spectrometry (ESI-MS), as well as the results obtained from
      screening of dynamic catalyst library of complexes L(a)/Ti/L(b) (L(a) or L(b) =
      chiral diol ligands). The BINOL-to-titanium ratio and the presence or absence of
      water in the catalytic system were found to exert profound influences on both
      reactivity and enantioselectivity of the reaction. The NLE studies revealed that
      the titanium species involved in the catalysis should contain more than one BINOL
      unit, either within or at the periphery of the catalytic cycle. ESI-MS analysis
      of the catalytic systems provided strong support in favor of the mechanistic
      proposal that titanium complexes bearing the Ti(BINOLate)2 moiety should be the
      active species responsible for the catalysis, which was further confirmed by the
      observation of synergistic effect of the heteroligand combinations during
      screening of the dynamic catalyst library. ESI-MS analysis of the reaction system
      indicated that water does not take part in the catalyst generation, which is an
      unprecedented finding in contrast to the previous mechanistic understandings in
      the titanium catalytic chemistry involving the participation of water. Most
      probably, water functions as a proton shuttle in the catalysis, facilitating the
      proton transfer between the reactants. Furthermore, the origin of (+)-NLE
      observed in the present catalytic system is rationalized on the basis of the ESI
      MS analysis of the catalyst system prepared from a 1:1 pseudoracemic mixture of
      (S)-BINOL and (R)-3,3',6,6'-D4-BINOL. Finally, the reactivity differences between
      several couples of epoxide/amine combinations were tentatively rationalized on
      the basis of the arguments on their relative coordination preferences, and
      several other aliphatic amines were also found to efficiently ring-open the
      titled epoxide in excellent enantioselectivities. The results from this study are
      expected to shed some light on the often elusive chemistry of Ti(IV)-based
      catalytic systems where water or molecular sieves (or alcohols, etc.) are found
      to play an important yet inexplicable role and may help the search for effective
      asymmetric Ti(IV) catalysts for other types of reactions.

PMID- 18616253
TI  - Reactions of a metallacyclobutene complex with alkenes.
AB  - The first productive reactions of a characterized metallacyclobutene complex with
      alkenes are reported. Thus, the metallacyclobutene complex (eta5
      C5H5)(PPh3)Co[kappa2-(C,C)-C(SO2Ph) C(Si(CH3)3)CH(CO2CH2CH3)] (2) undergoes
      reaction with alkenes to give 1,4-diene complexes with a high degree of regio-
      and stereoselectivity. A mechanism is proposed in which the metallacyclobutene
      generates a cyclic vinylcarbene intermediate that undergoes [4 + 2]-cycloaddition
      reactions with activated alkenes. A model of the vinylcarbene intermediate has
      been examined using quantum mechanical methods.

PMID- 18616254
TI  - Pi-dimer formation as the driving force for calix[4]arene-based molecular
      actuators.
AB  - Stable pi-dimers are formed upon oxidation of the model units of proposed
      calix[4]arene-based molecular actuators in a solvent of low dielectric constant
      (CH 2Cl 2) at room temperature. Evidence from UV-vis, EPR, and DPV are all in
      agreement with the pi-dimer formation. In addition, pi-dimer formation is
      dependent upon the conformational flexibility of the calix[4]arene hinge.

PMID- 18616255
TI  - Novel N,N,P-tridentate ligands for the highly enantioselective copper-catalyzed
      1,4-addition of dialkylzincs to enones.
AB  - Use of 0.25 mol % of the N, N, P-tridentate ligand containing the 2-quinolyl
      moiety ( 1 and 2) and 0.1 mol % of Cu(OTf) 2 enabled the enantioselective 1,4
      addition of dialkylzincs to cyclic enones to produce 1,4-adducts in up to 99% ee.

PMID- 18616256
TI  - Structure revision and synthesis of a novel labdane diterpenoid from Zingiber
      ottensii.
AB  - The structure of ottensinin, a recently reported constituent of the medicinal
      plant Zingiber ottensii, was revised by re-evaluation of available NMR data from
      alpha-ylidenebutenolide 1 to gamma-pyrone 2, whose rearranged labdane skeleton is
      unprecedented. Structure 2 was proven by synthesis from (+)-sclareolide (nine
      steps, 27% overall yield) and was further validated by X-ray diffraction analysis
      of our synthetic sample. A plausible biosynthesis of 2 is proposed.

PMID- 18616257
TI  - Catalytic enantioselective intermolecular cycloaddition of 2-diazo-3,6
      diketoester-derived carbonyl ylides with alkynes and styrenes using chiral
      dirhodium(II) carboxylates.
AB  - Dirhodium(II) tetrakis[ N-tetrachlorophthaloyl-( S)- tert-leucinate], Rh 2( S
      TCPTTL) 4, is an exceptionally effective catalyst for enantioselective tandem
      carbonyl ylide formation-cycloaddition reactions of 2-diazo-3,6-diketoesters with
      arylacetylene, alkoxyacetylene, and styrene dipolarophiles, providing
      cycloadducts in good to high yields and with enantioselectivities of up to 99% ee
      as well as with perfect exo diastereoselectivity for styrenes.

PMID- 18616258
TI  - Highly regioselective isomerization-hydroformylation of internal olefins to
      linear aldehyde using rh complexes with tetraphosphorus ligands.
AB  - A series of new pyrrole-based tetraphosphorus ligands were synthesized and used
      for Rh-catalyzed isomerization-hydroformylation of internal olefins. It was found
      that the substituents at the 3,3',5,5'-positions of the biphenyl greatly effected
      the linear selectivity, and the alkyl-substituted tetraphosphorus ligands gave
      the best results (for 2-octene, n: i up to 207, for 2-hexene, n: i up to 362).

PMID- 18616259
TI  - Expedient synthesis of pyrrolo[1,2-a]indoles: preparation of the core of
      yuremamine.
AB  - Pyrrolo[1,2- a]indoles are conveniently prepared from tetrahydro-1,2-oxazines,
      which in turn are generated through the reaction of nitrones with 1,1
      cyclopropanediesters. The synthetic route proves to be highly diastereoselective
      and provides access to the core of the recently discovered pyrrolo[1,2- a]indole
      natural product yuremamine.

PMID- 18616261
TI  - Neuroprotective effects of resveratrol on MPTP-induced neuron loss mediated by
      free radical scavenging.
AB  - Resveratrol is a natural polyphenol and possesses many biological functions such
      as anti-inflammatory activity and protection against atherosclerosis and
      myocardial infraction. Parkinson's disease is a common progressive
      neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is
      the most useful neurotoxin to induce Parkinsonism. The present study was carried
      out to elucidate the neuroprotective effect and possible mechanism of resveratrol
      on MPTP-induced striatal neuron loss. Sixty adult Balb/c mice were divided into
      four groups: sham operation, MPTP treatment (30 mg/kg, i.p.), MPTP combined with
      resveratrol administration (20 mg/kg, i.v.), and resveratrol treatment alone.
      Microdialysis and high-performance liquid chromatography were used to analyze
      dihydroxybenzoic acid (DHBA) that reflected the hydroxyl radical level. In the
      present study, we found MPTP chronic administration significantly induced motor
      coordination impairment in mice. After MPTP administration, the hydroxyl radical
      levels in substantia nigra were also significantly elevated and animals displayed
      severe neuronal loss. Resveratrol administration significantly protected mice
      from MPTP-induced motor coordination impairment, hydroxyl radical overloading,
      and neuronal loss. Our results demonstrated that resveratrol could elicit
      neuroprotective effects on MPTP-induced Parkinsonism through free radical
      scavenging.

PMID- 18616260
TI  - Phenolic compound concentration and antioxidant activities of edible and
      medicinal mushrooms from Korea.
AB  - A study was conducted to determine the content of phenolic compounds and the
      antioxidative activity of five edible and five medicinal mushrooms commonly
      cultivated in Korea. Phenolic compounds were analyzed using high performance
      liquid chromatography, and antioxidant activity was evaluated by 1,1-diphenyl-2
      picrylhydrazyl radical scavenging activity and superoxide dismutase activity. A
      total of 28 phenolic compounds were detected in the mushrooms studied. The
      average total concentration of phenolic compounds was 326 microg/g, the average
      being of 174 microg/g in edible mushrooms and 477 microg/g in medicinal
      mushrooms. The average total flavonoids concentration was 49 microg/g, with
      averages of 22 and 76 microg/g in edible and medicinal mushrooms, respectively.
      The DPPH radical scavenging activities ranged between 15 (Pleurotus eryngii) and
      70% (Ganoderma lucidum) when reaction time was for 1 min. When reaction time was
      30 min, the values ranged between 5 (Pleurotus eryngii) and 78% (Agaricus
      bisporus). The SOD activity averaged 28% among the 10 mushroom species, averages
      for edible and medicinal mushrooms being comparable. DPPH activities was
      significantly correlated (p < 0.01) with total content of phenolic compounds in
      edible mushrooms, while in medicinal mushrooms there was a significant
      correlation (p < 0.01) between SOD activity and total concentration of phenolic
      compounds. Numerous significant positive correlations were observed between
      phenolic compounds detected and antioxidative potential.

PMID- 18616262
TI  - Organic acid contents in onion cultivars (Allium cepa L.).
AB  - The following organic acids (glutamic, oxalic, pyruvic, malic, tartaric, citric,
      and fumaric), pungency, Brix degree, acidity, and pH were determined in onion
      cultivars (Texas, Guayonje, San Juan de la Rambla, Carrizal Alto, Carrizal Bajo,
      and Masca) harvested in the same agroclimatic conditions. Glutamic acid was the
      most abundant organic acid (325 +/- 133 mg/100 g) followed by citric acid (48.5
      +/- 24.1 mg/100 g) and malic acid (43.6 +/- 10.4 mg/100 g). There were
      significant differences between the onion cultivars in the mean concentrations of
      all of the analyzed parameters. The San Juan de la Rambla and Masca cultivars
      presented, in general, higher concentrations of the organic acids than the other
      cultivars. Significant differences in most of the analyzed parameters were
      observed between the two seed origins for the Masca and San Juan de la Rambla
      cultivars. The onion samples tended to be classified according to the cultivar
      and, in the case of San Juan de la Rambla cultivar, according to the precedence
      of the seeds after applying discriminant analysis.

PMID- 18616263
TI  - Targeting key aromatic substances on the typical aroma of sherry vinegar.
AB  - Two gas chromatography-olfactometry (GC-O) techniques were used to screen
      targeting compounds with an impact on the perceived quality of Sherry vinegar:
      detection frequency and aroma extract dilution analysis (AEDA). The GC-O study
      revealed the presence of 108 aromatic notes, of which 64 were identified.
      Diacetyl, isoamyl acetate, acetic acid, and sotolon reached the highest frequency
      and flavor dilution (FD) factors. Ethyl acetate accounted for the maximum
      frequency but only a FD factor of 4. To test the sensory impact of these
      odorants, they were added to a 7% (w/v) acetic acid solution. We determined
      similarity values (SV) between solutions and the Sherry vinegar. The highest
      value from the similarity test was observed when diacetyl, ethyl acetate, and
      sotolon were added simultaneously. The profile of this model solution and a
      representative Sherry vinegar showed good similarity in the general impression
      descriptor, which emphasizes the important contribution of these three compounds
      to the global aroma of this vinegar.

PMID- 18616264
TI  - Transfer and accumulation of persistent organochlorine compounds from bovine dams
      to newborn and suckling calves.
AB  - The maternal-fetal and neonatal transfers of polychlorinated dibenzo- p-dioxins
      (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated
      biphenyls (PCBs) were measured in the blood and milk of dams and in the blood of
      newborn and suckling calves. Calf blood toxic equivalent quantities (TEQs) were
      drastically increased by suckling. Blood concentrations of individual congeners
      were greater in suckling calves than in newborn calves, excluding
      octachlorodibenzo- p-dioxin (O 8CDD); O 8CDD did not readily transfer to milk but
      was readily absorbed by the gastrointestinal tract and remained in systemic
      circulation longer than other congeners. Congener concentrations in milk were
      correlated with maternal blood levels, and those in suckling calf blood were
      dependent on their concentrations in milk. These results suggest that neonatal
      calves absorb more lipophilic organochlorine compounds than prenatal fetuses,
      that those compounds that are transferred from dams to calves are associated not
      only with lipid transport but also with other carriers, and that the distribution
      of congeners is structure-dependent.

PMID- 18616266
TI  - Effects of hydrophilic and lipophilic beta-sitosterol derivatives on cholesterol
      absorption and plasma cholesterol levels in rats.
AB  - The effects of two phytosterol derivatives of beta-sitosterol, a lipophilic
      derivative (LPSS) and a hydrophilic derivative (HPSS), on cholesterol uptake and
      blood lipoprotein levels in rats were compared with those of beta-sitosterol.
      LPSS and HPSS have solubilities of up to 0.05 g/mL in edible oil and 0.15 g/mL in
      water at 25 degrees C, respectively. The intragastric administration of either 30
      or 50 mg of phytosterols with 10 mg of [4- (14)C]-cholesterol per kg of body
      weight once a day for 3 consecutive days reduced cholesterol uptake by
      approximately 30% compared to controls that received cholesterol alone. Feeding a
      cholesterol-enriched diet containing 1% or 3% beta-sitosterol, LPSS, or HPSS for
      2 and 4 weeks resulted in lowered levels of total blood cholesterol and reduced
      the atherogenic index in all groups. These results indicate that LPSS and HPSS
      have comparable effects to beta-sitosterol in lowering blood cholesterol levels
      but they differ from beta-sitosterol in having a solubility advantage.

PMID- 18616265
TI  - Design, synthesis, and fungicidal activity of macrolactones and macrolactams with
      a sulfonamide side chain.
AB  - Four series of novel macrolactones and macrolactams12-alkylsulfonamido-1,15
      pentadecanlactones ( 5), 12-alkylsulfonamido-15-methyl-1,15-pentadecanlactones (
      6), 12-alkylsulfonamido-1,15-pentadecanlactams ( 7), and N
      (alkylsulfonamidoethyl)-1,12-dodecanlactams ( 8)were designed and synthesized
      from readily available 2-nitrocyclododecanone or cyclododecanone. Their
      structures were confirmed by (1)H NMR, IR, and elemental analysis. The bioassay
      showed that these compounds displayed fair to excellent fungicidal activity
      against Rhizoctonia solani Kuhn and have a gradual increase of fungicidal
      activity in the order of 6, 7, 8, and 5. Among them, compounds 5a, 5b, and 5c
      displayed excellent fungicidal activity against R. solani comparable with the
      commercial fungicide carbendazim. Above results illustrated that the rule on the
      relationship between the activity and hydrogen-bonding, namely the macrocyclic
      compounds with a hydrogen-bonding acceptor and a hydrogen-bonding donor on the
      ring and having a three methylenes distance between two polarizable groups have
      the best fungicidal activity against R. solani, has a general suitability to the
      macrocyclic compounds, and pesticide molecules may combine with a target enzyme
      by hydrogen-bonding. The facts, which compound 6 has a much lower fungicidal
      activity against R. solani than compound 5 but their difference in chemical
      structure is only that there is a methyl group on the C15 for compound 6 and none
      but hydrogen atom on the C15 for compound 5, indicated that a methyl group plays
      an inhibitory role to the fungicidal activity. It suggests that the existence of
      a methyl group with a great volume between two polarizable groups would interfere
      in the interaction of pesticide molecules and the target enzyme.

PMID- 18616267
TI  - Changes in the fatty acid and triacylglycerol profiles in the subcutaneous fat of
      Iberian ham during the dry-curing process.
AB  - In this study, we have evaluated the changes that occur in the profiles of total
      fatty acids and triacylglycerols during the dry-curing process (730 days) of
      Iberian ham. The subcutaneous adipose tissues of six hams obtained from three
      Iberian pigs fed on acorns were analyzed periodically during the processing time
      (from the raw to the dry-cured samples), including postsalting, drying, and
      ripening stages. The environmental conditions were also registered. The curing
      process significantly decreased (p < 0.01) the relative percentages of total
      polyunsaturated fatty acids, including C18:2n-6 and C18:3n-3 and, therefore,
      significantly increased (p < 0.05) the level of monounsaturated fatty acids. The
      triglycerides containing 0-2 double bonds showed an increase during the curing
      process. On the contrary, the more unsaturated ones (3-5 double bonds) suffered a
      significant decrease. We have postulated that these changes could also be due to
      polymerization and oxidation reactions that affect the triacylglycerols and
      besides the fatty acids. In general, most fatty acids and triacylglycerols
      reversed the trend by about 500-600 days of processing.

PMID- 18616268
TI  - Multi-level approach for the analysis of water effects in corn flakes.
AB  - The purpose of this work was to analyze the effect of water on thermal
      transitions, mechanical properties, and molecular mobility in corn flakes (CF),
      and their relationships. Commercial common (CCF) and sugar-frosted (SCF) corn
      flakes were studied in a water content (wc) range from 5 to 20 (% dry basis). The
      slope of (1)H NMR spin-spin relaxation time T 2* (determined by FID) versus
      temperature plot changed close to T g. Compression force showed a maximum at wc
      of ca. 12 and 16% (db) for SCF and CCF, respectively. (1)H NMR complemented DSC
      data in determining the temperature dependence of water and solid mobility, in
      order to assess quality of laminated corn products. The results of the present
      work indicate that while the compression force showed a maximum value as a
      function of water content, T g values determined by DSC or by spin-spin
      relaxation decreased progressively with increasing water content.

PMID- 18616269
TI  - The xanthophyll composition of biofortified maize (Zea mays Sp.) does not
      influence the bioefficacy of provitamin a carotenoids in Mongolian gerbils
      (Meriones unguiculatus).
AB  - Maize has been targeted for biofortification with provitamin A carotenoids
      through traditional breeding. Two studies were conducted in gerbils to evaluate
      factors that may affect provitamin A activity. Maize diets had equal theoretical
      concentrations of vitamin A (VA) assuming 100% bioefficacy. Study 1 ( n = 57)
      varied the ratio of beta-cryptoxanthin and beta-carotene but maintained the same
      theoretical VA. Study 2 ( n = 67) varied lutein and zeaxanthin. Other treatments
      were oil, VA, or beta-carotene doses. Serum and livers were analyzed for VA and
      carotenoids. In study 1, total liver VA did not differ among the maize groups. In
      study 2, total liver VA of the VA and maize groups were higher than controls ( P
      < 0.05). Conversion factors were 2.1-3.3 mug beta-carotene equivalents to 1 mug
      retinol. Twice the molar amount of beta-cryptoxanthin was as efficacious as beta
      carotene and the proportion of beta-cryptoxanthin or xanthophylls did not
      appreciably change the VA value of biofortified maize.

PMID- 18616270
TI  - Determination of coenzyme Q10 and Q9 in vegetable oils.
AB  - A new sensitive and selective method has been developed for the quantification of
      the total coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) concentration in vegetable
      oil samples. The coenzyme Q fraction is isolated by solid-phase extraction (SPE)
      on amino phase eluting with a mixture of heptane:ethyl ether. The organic solvent
      is evaporated under nitrogen, and the residue is dissolved in a mixture of
      acetonitrile:tetrahydrofuran and finally is analyzed by reverse-phase high
      performance liquid chromatography with a mass detector. The sensitivity of the
      method is based on the high efficient formation of the radical anions [M (-.)] of
      CoQ9 and CoQ10 by negative atmospheric pressure ionization. Interferences are
      minimized by using mass detection of the [M (-.)] ions ( m/ z = 797.5 for CoQ9
      and m/ z = 862.5 for CoQ10) in selective reaction monitoring mode ( m/ z = 797.5 
      -> m/ z = 779.5 and m/ z = 862.5 --> m/ z = 847.5) using a triple-quadrupole mass
      spectrometer. The method was successfully applied to sunflower, soybean, and
      rapeseed oils, with a limit of quantification of 0.025 mg/kg for both compounds.

PMID- 18616271
TI  - Detection of SNPs in fish DNA: application of the fluorogenic ribonuclease
      protection (FRIP) assay for the authentication of food contents.
AB  - The fluorogenic ribonuclease protection (FRIP) assay was used to detect single
      nucleotide polymorphisms (SNPs) in commercially produced fish products. By using
      fluorescence resonance energy transfer (FRET) between fluorophore and quencher
      labeled probes, the species-specific cleavage of sample RNA was detected by
      measuring the fluorescence intensity during the FRIP assay. We were able to
      discriminate raw and thermally processed eel and tuna species using the FRIP
      based SNP detection method. Furthermore, the intensity of fluorescence was
      correlated with the mutant/wild-type ratio. These results suggest that the FRIP
      assay is a useful method for the in situ confirmation of labels of fishery foods
      during food production.

PMID- 18616272
TI  - Genetic and environmental factors affecting allergen-related gene expression in
      apple fruit (Malus domestica L. Borkh).
AB  - Freshly consumed apples can cause allergic reactions because of the presence of
      four classes of allergens, namely, Mal d 1, Mal d 2, Mal d 3, and Mal d 4, and
      their cross-reactivity with sensitizing allergens of other species. Knowledge of
      environmental and endogenous factors affecting the allergenic potential of apples
      would provide important information to apple breeders, growers, and consumers for
      the selection of hypoallergenic genotypes, the adoption of agronomical practices
      decreasing the allergenic potential, and the consumption of fruits with reduced
      amount of allergens. In the present research, expression studies were performed
      by means of real-time PCR for all the known allergen-encoding genes in apple.
      Fruit samples were collected from 15 apple varieties and from fruits of three
      different trials, set up to assess the effect of shadowing, elevation, storage,
      and water stress on the expression of allergen genes. Principal components
      analysis (PCA) was performed for the classification of varieties according to
      gene expression values, pointing out that the cultivars Fuji and Brina were two
      good hypoallergenic candidates. Shadowing, elevation, and storage significantly
      affected the transcription of the allergen-encoding genes, whereas water stress
      slightly influenced the expression of only two genes, in spite of the dramatic
      effect on both fruit size and vegetative growth of the trees. In particular,
      shadowing may represent an important cultural practice aimed at reducing apple
      cortex allergenicity. Moreover, elevation and storage may be combined to reduce
      the allergenic potential of apple fruits. The possible implications of the
      results for breeders, growers, and consumers are discussed critically.

PMID- 18616273
TI  - LC-MS analysis of solanidane glycoalkaloid diversity among tubers of four wild
      potato species and three cultivars (Solanum tuberosum).
AB  - Secondary metabolites in potato tubers include both phytonutrients and plant
      defense compounds. The extent these small molecules vary among different potato
      genotypes is not well characterized. LC-MS analysis of tuber extracts from seven
      potato genotypes showed that one large source of small molecule variation is the
      glycoalkaloids. Glycoalkaloids are involved in the resistance of potatoes to
      pathogens and pests, but they also have implications for human health and
      nutrition. This study focused on glycoalkaloids with solanidane or solanidane
      like aglycones, of which over 50 were tentatively identified, many of which
      appeared to be novel glycoalkaloids. Results suggested the variety of
      glycoalkaloids in potatoes is considerably greater than previously thought.
      Dissecting the role of these many glycoalkaloids in human health or pest and
      pathogen resistance will be a formidable undertaking.

PMID- 18616274
TI  - Extraction of up to 95% of wheat (Triticum aestivum) flour protein using warm
      sodium dodecyl sulfate (SDS) without reduction or sonication.
AB  - Extraction of glutenin polymers without sonication is an essential prerequisite
      for accurate determination of their composition and molecular size distribution.
      Sequential fractionation of wheat flour with 0.1 M KCl and 0.25% sodium dodecyl
      sulfate (SDS) at 21 degrees C and 2% SDS at 60 degrees C extracted up to 95% of
      total protein. We propose that 2% SDS at 60 degrees C disrupts hydrogen bonds in
      glutenin and gliadin aggregates, reduces hydrophobic interactions, and
      facilitates solubilization. Analysis by size-exclusion high-performance liquid
      chromatography (SE-HPLC), reverse-phase (RP)-HPLC, and SDS-polyacrylamide gel
      electrophoresis (PAGE) revealed that partitioning of gliadins and glutenins among
      the extracts differed for two flours with good baking quality (Butte 86 and
      Jagger) and one with poor baking quality (Chinese Spring). More gliadin was
      associated with the 0.25% SDS extract for Chinese Spring, whereas more gliadin
      was associated with the 2% SDS extract for Butte 86 and Jagger. Unextractable
      glutenin polymer was only 4-5% of total protein for Butte 86 and Chinese Spring
      and 14% for Jagger.

PMID- 18616275
TI  - DNA damage after acute and chronic treatment with malathion in rats.
AB  - Malathion is an insecticide widely used in agriculture and in public health
      programs that when used indiscriminately in large amounts can cause environmental
      pollution and risk to human health. However, it is possible that during the
      metabolism of malathion, reactive oxygen species can be generated, and malathion
      may produce oxidative stress in intoxicated rats that can be responsible for
      alterations in DNA molecules related in some studies. As a result, the present
      study aimed to investigate the DNA damage of cerebral tissue and peripheral blood
      in rats after acute and chronic malathion exposure. We used single cell gel
      electrophoresis (Comet assay) to measure early damage in hippocampus and
      peripheral blood and the Micronucleus test in total erythrocytes samples.
      Malathion was administered intraperitoneally once a day for one day (acute) or
      for 28 days (chronic) protocols (in both protocols, malathion was administered at
      25, 50, 100, and 150 mg/kg). Our results showed that malathion (100 and 150
      mg/kg) increased the DNA damage index in the peripheral blood and in the
      hippocampus after both chronic and acute treatment. Malathion increased the
      frequency of micronuclei only in chronic treatment at 150 mg/kg dose, and induced
      a cytotoxic dose-dependent decrease in the frequency of polychromatic
      erythrocytes in the peripheral blood of rats. In conclusion, since malathion
      increased both the peripheral blood and hippocampus DNA damage index using the
      Comet assay and increased the frequency of micronuclei in the total peripheral
      blood, it can be regarded as a potential mutagen/carcinogenic agent.

PMID- 18616276
TI  - ELISA for sulfonamides and its application for screening in water contamination.
AB  - Two enzyme-linked immunosorbent assays (ELISAs) were tested for their suitability
      for detecting sulfonamides in wastewater from various stages in wastewater
      treatment plants (WWTPs), the river into which the wastewater is discharged, and
      two swine-rearing facilities. The sulfamethoxazole ELISA cross-reacts with
      several compounds, achieving detection limits of <0.04 microg/L for
      sulfamethoxazole (SMX), sulfamethoxypyridine, sulfachloropyridine, and
      sulfamethoxine, whereas the sulfamethazine (SMZ) ELISA is more compound specific,
      with a detection limit of <0.03 microg/L. Samples from various stages of
      wastewater purifications gave 0.6-3.1 microg/L by SMX-ELISA, whereas river
      samples were approximately 10-fold lower, ranging from below detection to 0.09
      microg/L. Swine wastewater samples analyzed by the SMX-ELISA were either at or
      near detectable limits from one facility, whereas the other facility had
      concentrations of approximately 0.5 microg/L, although LC-MS/MS did not confirm
      the presence of SMX. Sulfamethazine ELISA detected no SMZ in either WWTP or river
      samples. In contrast, wastewater samples from swine facilities analyzed by SMZ
      ELISA were found to contain approximately 30 microg/L [piglet (50-100 lb)
      wastewater] and approximately 7 microg/L (market-weight hog wastewater).
      Sulfamethazine ELISA analyses of wastewater from another swine facility found
      concentrations to be near or below detection limits. A solid phase extraction
      method was used to isolate and concentrate sulfonamides from water samples prior
      to LC-MS/MS multiresidue confirmatory analysis. The recoveries at 1 microg/L
      fortification ranged from 42 +/- 4% for SMZ to 88 +/- 4% for SMX ( n = 6). The
      ELISA results in the WWTPs were confirmed by LC-MS/MS, as sulfonamide
      multiresidue confirmatory analysis identified SMX, sulfapyridine, and
      sulfasalazine to be present in the wastewater. Sulfamethazine presence at one
      swine-rearing facility was also confirmed by LC-MS/MS, demonstrating the
      usefulness of the ELISA technique as a rapid and high-throughput screening
      method.

PMID- 18616277
TI  - Antioxidant effects of phlorotannins isolated from Ishige okamurae in free
      radical mediated oxidative systems.
AB  - Three phlorotannins, including phloroglucinol, diphlorethohydroxycarmalol, and
      6,6'-bieckol, were isolated from Ishige okamurae by column chromatography. The
      structures of the phlorotannins were determined on the basis of spectroscopic
      analysis, including NMR and mass spectrometry (MS) techniques. Antioxidant
      effects of phlorotannins were measured by direct free radical scavenging
      activities using the electron spin resonance spectrometry (ESR) technique and
      cellular systems in vitro. The results indicated that diphlorethohydroxycarmalol
      and 6,6'-bieckol showed potential radical scavenging activities against the 2,2
      diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, alkyl, and superoxide radicals.
      Moreover, no cytotoxicities of the phlorotannins on human fetal lung fibroblasts
      cell line (MRC-5), mouse macrophages cell line (RAW264.7), and human leukemic
      cell line (HL-60) were observed. In addition, diphlorethohydroxycarmalol and 6,6'
      bieckol significantly reduced the intracellular reactive oxygen species level
      assessed by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay in RAW264.7
      cells, and myeloperoxide (MPO) activity in HL-60 cells and radical-mediated
      oxidation of cell membrane proteins in RAW264.7 cells were dose-dependently
      inhibited in the presence of diphlorethohydroxycarmalol and 6,6'-bieckol. In
      conclusion, these results suggested that phlorotannins could be used as novel
      functional foodstuffs or antioxidants in the cosmetic and drug industries.

PMID- 18616279
TI  - Strategy for determination of in vitro protein acetylation sites by using isotope
      labeled acetyl coenzyme A and liquid chromatography-mass spectrometry.
AB  - Acetylation of proteins on specific lysine residues by acetyltransferase enzymes
      is a post-translational modification for biologically relevant regulation. In
      this study, we proposed a strategy to determine the in vitro acetylation sites of
      proteins by tracing isotope-labeled acetyl groups using mass spectrometry.
      Isotope-labeled and unlabeled acetyl groups transferred onto the substrates in
      vitro result in a specific "mass difference" that can be measured by MS analysis
      and utilized for localization of potential acetylated peptide signals. The
      identification of acetylation site is facilitated by conducting MS/MS experiments
      on those selected signals. Acetylation reactions of substrates were performed in
      the presence of acetyltransferase and equal molar of isotope-labeled acetyl
      coenzyme A ([(13)C2-2-D3]-acetyl-CoA) and unlabeled acetyl-CoA. After enzymatic
      digestion, the resulting peptide mixture was fractionated by off-line, reversed
      phase high-pressure liquid chromatography and the accurate mass measurement of
      peptides was achieved by a quadrupole/time-of-flight mass spectrometer. Signals
      with 5-Da (or their multiples) mass differences and equal responses were selected
      out by program computation. Those potential acetylated peptide signals were
      subjected to MS/MS analyses for determination of acetylation sites. We have used
      histone H3 peptide (aa 1-20), histone H2B peptide (aa 1-21), histone H2A, and
      histone H2B proteins as the model compounds to demonstrate the applicability of
      this analytical scheme for the characterization of in vitro acetylation sites.

PMID- 18616278
TI  - Biodistribution and pharmacokinetic analysis of Paclitaxel and ceramide
      administered in multifunctional polymer-blend nanoparticles in drug resistant
      breast cancer model.
AB  - In this study, we have investigated the biodistribution and pharmacokinetic
      analysis of paclitaxel (PTX) and the apoptotic signaling molecule, C6-ceramide
      (CER), when administered in a multifunctional polymer-blend nanoparticle
      formulation to female nude mice bearing an orthotopic drug sensitive MCF7 and
      multidrug resistant MCF7 TR (MDR-1 positive) human breast adenocarcinoma. A
      polymer-blend nanoparticle system was engineered to incorporate temporally
      controlled sequential release of the combination drug payload. Hereby, PTX was
      encapsulated in the pH-responsive rapid releasing polymer, poly(beta-amino ester)
      (PbAE), while CER was present in the slow releasing polymer, poly(D,L-lactide-co
      glycolide) (PLGA) within these blend nanoparticles. When particle formulations
      were administered intravenously to MCF7 and MCF7 TR tumor bearing mice, higher
      concentrations of PTX were found in the blood due to longer retention time and an
      enhanced tumor accumulation relative to administration of free drug. In addition,
      the PLGA/PbAE blend nanoparticles were effective in enhancing the residence time
      of both drugs at the tumor site by reducing systemic clearance. Overall, these
      results are highly encouraging for development of multifunctional polymer-blend
      nanoparticle formulations that can be used for temporal-controlled administration
      of two drugs from a single formulation.

PMID- 18616280
TI  - Bacterial ApbC can bind and effectively transfer iron-sulfur clusters.
AB  - The metabolism of iron-sulfur ([Fe-S]) clusters requires a complex set of
      machinery that is still being defined. Mutants of Salmonella enterica lacking
      apbC have nutritional and biochemical properties indicative of defects in [Fe-S]
      cluster metabolism. ApbC is a 40.8 kDa homodimeric ATPase and as purified
      contains little iron and no acid-labile sulfide. An [Fe-S] cluster was
      reconstituted on ApbC, generating a protein that bound 2 mol of Fe and 2 mol of S
      (2-) per ApbC monomer and had a UV-visible absorption spectrum similar to known
      [4Fe-4S] cluster proteins. Holo-ApbC could rapidly and effectively activate
      Saccharomyces cerevisiae apo-isopropylmalate isolomerase (Leu1) in vitro, a
      process known to require the transfer of a [4Fe-4S] cluster. Maximum activation
      was achieved with 2 mol of ApbC per 1 mol of apo-Leu1. This article describes the
      first biochemical activity of ApbC in the context of [Fe-S] cluster metabolism.
      The data herein support a model in which ApbC coordinates an [4Fe-4S] cluster
      across its dimer interface and can transfer this cluster to an apoprotein acting
      as an [Fe-S] cluster scaffold protein, a function recently deduced for its
      eukaryotic homologues.

PMID- 18616281
TI  - Functional characterization of the Shigella dysenteriae heme ABC transporter.
AB  - The heme ATP binding cassette (ABC) transporter, ShuUV, of Shigella dysenteriae
      has been incorporated into proteoliposomes. Functional characterization of ShuUV
      revealed that ATP hydrolysis and transport of heme from the periplasmic binding
      protein, ShuT, to the cytoplasmic binding protein, ShuS, are coupled. Site
      directed mutagenesis of ShuT residues proposed to be required for stabilization
      of the complex abolished heme transport. Furthermore, residues His-252 and His
      262, located in the translocation channel of ShuU, were required for the release
      of heme from ShuT and translocation to ShuS. The initial functional
      characterization of an in vitro heme uptake system provides a platform for future
      spectroscopic studies.

PMID- 18616282
TI  - Brucella abortus MFP: a trimeric coiled-coil protein with membrane fusogenic
      activity.
AB  - The bacterial genus Brucella consists of a group of facultative intracellular
      pathogens which produces abortion and infertility in animals and a chronic
      debilitating febrile illness in humans. BMFP is a basic protein of Brucella
      abortus that belongs to a highly conserved group of homologue proteins of unknown
      structure and function in proteobacteria (COG2960). In this study, we report the
      structural and biochemical characterization of this protein. We found that BMFP
      has two structural domains: a carboxyl-terminal coiled-coil domain through which
      the protein self-associates as a trimer and a natively disordered amino-terminal
      domain which has propensity to adopt an amphipathic alpha-helical structure. This
      natively unfolded domain undergoes a structural rearrangement from unfolded to
      alpha-helix in the presence of high ionic strength, acidic pH, detergents, and
      phospholipid vesicles. Moreover, we demonstrated that the interaction of BMFP
      with phospholipid vesicles promotes in vitro membrane fusion. These results
      contribute to the elucidation of the structural and functional properties of this
      protein and its homologues present in most proteobacteria.

PMID- 18616283
TI  - Remarkable stabilization of a psychrotrophic RNase HI by a combination of
      thermostabilizing mutations identified by the suppressor mutation method.
AB  - Ribonuclease HI from the psychrotrophic bacterium Shewanella oneidensis MR-1 (So
      RNase HI) is much less stable than Escherichia coli RNase HI (Ec-RNase HI) by
      22.4 degrees C in T m and 12.5 kJ mol (-1) in Delta G(H 2O), despite their high
      degrees of structural and functional similarity. To examine whether the stability
      of So-RNase HI increases to a level similar to that of Ec-RNase HI via
      introduction of several mutations, the mutations that stabilize So-RNase HI were
      identified by the suppressor mutation method and combined. So-RNase HI and its
      variant with a C-terminal four-residue truncation (154-RNase HI) complemented the
      RNase H-dependent temperature-sensitive (ts) growth phenotype of E. coli strain
      MIC3001, while 153-RNase HI with a five-residue truncation could not. Analyses of
      the activity and stability of these truncated proteins suggest that 153-RNase HI
      is nonfunctional in vivo because of a great decrease in stability. Random
      mutagenesis of 153-RNase HI using error-prone PCR, followed by screening for the
      revertants, allowed us to identify six single suppressor mutations that make 153
      RNase HI functional in vivo. Four of them markedly increased the stability of the
      wild-type protein by 3.6-6.7 degrees C in T m and 1.7-5.2 kJ mol (-1) in Delta
      G(H 2O). The effects of these mutations were nearly additive, and combination of
      these mutations increased protein stability by 18.7 degrees C in T m and 12.2 kJ
      mol (-1) in Delta G(H 2O). These results suggest that several residues are not
      optimal for the stability of So-RNase HI, and their replacement with other
      residues strikingly increases it to a level similar to that of the mesophilic
      counterpart.

PMID- 18616284
TI  - Helix mutations stabilize a late productive intermediate on the folding pathway
      of ubiquitin.
AB  - We have investigated the relative placement of rate-limiting energy barriers and
      the role of productive or obstructive intermediates on the folding pathway of
      yeast wild-type ubiquitin ( wt-Ub) containing the F45W mutation. To manipulate
      the folding barriers, we have designed a family of mutants in which stabilizing
      substitutions have been introduced incrementally on the solvent-exposed surface
      of the main alpha-helix (residues 23-34), which has a low intrinsic helical
      propensity in the native sequence. Although the U --> I and I --> N transitions
      are not clearly delineated in the kinetics of wt-Ub, we show that an intermediate
      becomes highly populated and more clearly resolved as the predicted stability of
      the helix increases. The observed acceleration in the rate of folding correlates
      with helix stability and is consistent with the I-state representing a productive
      rather than misfolded state. A Leffler analysis of the effects on kinetics of
      changes in stability within the family of helix mutants results in a biphasic
      correlation in both the refolding and unfolding rates that suggest a shift from a
      nucleation-condensation mechanism (weakly stabilized helix) toward a diffusion
      collision model (highly stabilized helix). Through the introduction of helix
      stabilizing mutations, we are able to engineer a well-resolved I-state on the
      folding pathway of ubiquitin which is likely to be structurally distinct from
      that which is only weakly populated on the folding pathway of wild-type
      ubiquitin.

PMID- 18616285
TI  - QacR-cation recognition is mediated by a redundancy of residues capable of charge
      neutralization.
AB  - The Staphylococcus aureus multidrug binding protein QacR binds to a broad
      spectrum of structurally dissimilar cationic, lipophilic drugs. Our previous
      structural analyses suggested that five QacR glutamic acid residues are critical
      for charge neutralization and specification of certain drugs. For example, E57
      and E58 interact with berberine and with one of the positively charged moieties
      of the bivalent drug dequalinium. Here we report the structural and biochemical
      effects of substituting E57 and E58 with alanine and glutamine. Unexpectedly,
      individual substitutions of these residues did not significantly affect QacR drug
      binding affinity. Structures of QacR(E57Q) and QacR(E58Q) bound to dequalinium
      indicated that E57 and E58 are redundant for charge neutralization. The most
      significant finding was that berberine was reoriented in the QacR multidrug
      binding pocket so that its positive charge was neutralized by side chain oxygen
      atoms and aromatic residues. Together, these data emphasize the remarkable
      versatility of the QacR multidrug binding pocket, illustrating that the capacity
      of QacR to bind myriad cationic drugs is largely governed by the presence in the
      pocket of a redundancy of polar, charged, and aromatic residues that are capable
      of electrostatic neutralization.

PMID- 18616286
TI  - Role of sequence bias in the topology of the multidrug transporter EmrE.
AB  - EmrE is the prototype of small multidrug resistance transporters and has emerged
      as a model of membrane protein evolution. Analysis of the distances separating
      symmetry-related site-specific spin labels, correlation of topological sequence
      bias to C-terminal orientation, to membrane insertion efficiency, and to
      resistance to ethidium bromide collectively demonstrate that EmrE monomers adopt
      a parallel topology in the functional dimer. We propose a coupled insertion and
      assembly model for EmrE in which the favorable energetics of the parallel dimer
      interface override topological constraints arising from weak asymmetry in
      positive charge distribution.

PMID- 18616287
TI  - A small molecule, Lys-Ala-7-amido-4-methylcoumarin, facilitates RNA dimer
      maturation of a stem-loop 1 transcript in vitro: structure-activity relationship
      of the activator.
AB  - The type 1 human immunodeficiency virus (HIV-1), like all retroviruses, contains
      two copies of the RNA genome as a dimer. A dimer initially forms via a self
      complementary sequence in the dimer initiation site (DIS) of the genomic RNA, but
      that dimer is converted to a mature dimer in a process generally promoted by the
      viral nucleocapsid (NC) protein. Formation of the mature dimer is correlated with
      infectivity. Study of genomic dimerization has been facilitated by discovery of
      short RNA transcripts containing the DIS stem-loop 1 (SL1), which can dimerize
      spontaneously without any protein factors in vitro as well as via the NC protein.
      On the basis of the palindromic nature of the apical loop of SL1, a kissing loop
      model has been proposed. First, a metastable kissing dimer is formed via a loop
      loop interaction and then converted into a more stable extended dimer by the NC
      protein. This dimerization process in vitro is believed to mimic the in vivo RNA
      maturation. During experimental screening of potential inhibitors, we discovered
      a small molecule, Lys-Ala-7-amido-4-methylcoumarin (KA-AMC), which facilitates
      the in vitro conversion from kissing dimer to extended dimer. Here we report the
      structure-activity relationship for KA-AMC for promoting dimer maturation.
      Guanidino groups and increasing positive charge on the side chain enhance
      activity. For activity, the charged side chain is preferred on the benzene ring,
      and O 1 in the coumarin scaffold is essential. NMR studies show that the coumarin
      derivatives stack with aromatic bases of the RNA. The coumarin derivatives may
      aid in the investigation of some aspects of dimer maturation and serve as a
      scaffold for design of maturation inhibitors or of activators of premature
      maturation, either of which can lead to a potential HIV therapeutic.

PMID- 18616288
TI  - AFM: a nanotool in membrane biology.
AB  - Cellular membranes are vital for life. They confine cells and cytosolic
      compartments and are involved in virtually every cellular process. Cellular
      membranes form cellular contacts and focal adhesions, anchor the cytoskeleton,
      generate energy gradients, transform energy, transduce signals, move cells, and
      actively form compartments to assemble different membrane proteins into
      functional entities. But how do cellular membranes perform these tasks? What do
      the machineries of cellular membranes look like, and how are they controlled and
      guided? Atomic force microscopy (AFM) allows the observation of biological
      surfaces in their native environment at a signal-to-noise ratio superior to that
      of any optical microscopic technique. With a spatial resolution approaching
      approximately 1 nm, AFM can identify the supramolecular assemblies,
      characteristic structure, and functional conformation of native membrane
      proteins. In recent years, AFM has evolved from imaging applications to a
      multifunctional "laboratory on a tip" that allows observation and manipulation of
      the machineries of cellular membranes. In the force spectroscopy mode, AFM
      detects interactions between two single cells at molecular resolution. Force
      spectroscopy can also be used to probe the local elasticity, chemical groups, and
      receptor sites of live cells. Other applications locate molecular interactions
      driving membrane protein folding, assembly, and their switching between
      functional states. It is also possible to examine the energy landscape of
      biomolecular reactions, as well as reaction pathways, associated lifetimes, and
      free energy. In this review, we provide a flavor of the fascinating opportunities
      offered by the use of AFM as a nanobiotechnological tool in modern membrane
      biology.

PMID- 18616289
TI  - Formation of purine-purine mispairs by Sulfolobus solfataricus DNA polymerase IV.
AB  - DNA damage that stalls replicative polymerases can be bypassed with the Y-family
      polymerases. These polymerases have more open active sites that can accommodate
      modified nucleotides. The lack of protein-DNA interactions that select for Watson
      Crick base pairs correlate with the lowered fidelity of replication. Interstrand
      hydrogen bonds appear to play a larger role in dNTP selectivity. The mechanism by
      which purine-purine mispairs are formed and extended was examined with Solfolobus
      solfataricus DNA polymerase IV, a member of the RAD30A subfamily of the Y-family
      polymerases, as is pol eta. The structures of the purine-purine mispairs were
      examined by comparing the kinetics of mispair formation with adenine versus 1
      deaza- and 7-deazaadenine and guanine versus 7-deazaguanine at four positions in
      the DNA, the incoming dNTP, the template base, and both positions of the terminal
      base pair. The time course of insertion of a single dNTP was examined with a
      polymerase concentration of 50 nM and a DNA concentration of 25 nM with various
      concentrations of dNTP. The time courses were fitted to a first-order equation,
      and the first-order rate constants were plotted against the dNTP concentration to
      produce k pol and K d (dNTP) values. A decrease in k pol/ K d (dNTP) associated
      with the deazapurine substitution would indicate that the position is involved in
      a crucial hydrogen bond. During correct base pair formation, the adenine to 1
      deazaadenine substitution in both the incoming dNTP and template base resulted in
      a >1000-fold decrease in k pol/ K d (dNTP), indicating that interstrand hydrogen
      bonds are important in correcting base pair formation. During formation of purine
      purine mispairs, the k pol/ K d (dNTP) values for the insertion of dATP and dGTP
      opposite 7-deazaadenine and 7-deazaguanine were decreased >10-fold with respect
      to those of the unmodified nucleotides. In addition, the rate of incorporation of
      1-deaza-dATP opposite guanine was decreased 5-fold. These results suggest that
      during mispair formation the newly forming base pair is in a Hoogsteen geometry
      with the incoming dNTP in the anti conformation and the template base in the syn
      conformation. These results indicate that Dpo4 holds the incoming dNTP in the
      normal anti conformation while allowing the template nucleotide to change
      conformations to allow reaction to occur. This result may be functionally
      relevant in the replication of damaged DNA in that the polymerase may allow the
      template to adopt multiple configurations.

PMID- 18616290
TI  - The Asp285 variant of DNA polymerase beta extends mispaired primer termini via
      increased nucleotide binding.
AB  - Endogenous DNA damage occurs at a rate of at least 20,000 lesions per cell per
      day. Base excision repair (BER) is a key pathway for maintaining genome
      stability. Several pol beta variants were identified as conferring resistance to
      3'-azido-3'-deoxythymidine (AZT) in Escherichia coli (Kosa et al. (1999) J. Biol.
      Chem. 274, 3851-3858). Detailed biochemical studies on one of these AZT-resistant
      variants, His285 to Asp, have shown that the H285D variant of pol beta possesses
      pre-steady-state kinetics that are similar to the wild-type polymerase. In gap
      filling assays with 5-bp gapped DNA, H285D showed a slight mutator phenotype. In
      depth single turnover kinetic analysis revealed that H285D is much more efficient
      than wild-type pol beta at extending mispaired primer termini. This mispair
      extension property of H285D is attributed to a greatly increased binding to the
      next correct nucleotide in the presence of a mispair. This change in K
      d(dNTP),app is not accompanied by a change in k pol; values for k pol are the
      same for both H285D and wild-type. Close examination of available structural
      data, as well as molecular modeling, has shown that residue 285 is able to make
      several stabilizing contacts in the fingers domain of the polymerase, and the
      introduction of a negatively charged side chain could have important effects on
      the enzyme. It is postulated that the loss of the contact between His285, Lys289,
      and Ile323 is responsible for the ability of H285D to extend mispairs through
      disruption of contacts near the C-terminal end of pol beta and propagation into
      the nucleotide binding pocket.

PMID- 18616291
TI  - Leukotriene A4 metabolites are endogenous ligands for the Ah receptor.
AB  - In addition to orchestrating an adaptive metabolic response to xenobiotic
      compounds, the aryl hydrocarbon receptor (AHR) also plays a necessary role in the
      normal physiology of mice. The AHR is activated by a structurally diverse group
      of chemicals ranging from carcinogenic environmental pollutants to dietary
      metabolites and a number of endogenous molecules. Leukotriene A 4 (5,6-LTA 4)
      metabolites were identified in DRE-driven luciferase reporter assays as
      activators of AHR signaling. Various LTA 4 metabolites, including several 5,6-
      and 5,12-DiHETE products, were screened for AHR activity with 6- trans-LTB 4, 6-
      trans-12- epi-LTB 4, 5( S),6( S)-DiHETE, and 5( S),6( R)-DiHETE eliciting a
      significant level of AHR transcriptional activity. However, electrophoretic
      mobility shift assays (EMSAs) revealed that only 5,6-DiHETE isomers were capable
      of directly binding and activating the AHR to a DNA-binding species in vitro.
      Furthermore, ligand competition binding experiments confirm the ability of these
      compounds to directly bind to the AHR. Interestingly, "aged" preparations of 5,6
      DiHETE isomers produced an enhanced level of AHR activation while demonstrating
      an increase in binding affinity for the receptor. Although the reason for this
      has not been fully determined, the formation of geometric isomers in the
      conjugated triene region of these molecules may play a role in the observed
      increase in AHR-mediated transcriptional activity. This work suggests a
      connection between AHR activation and inflammatory signaling molecules produced
      by the 5-lipoxygenase pathway.

PMID- 18616292
TI  - Structural transitions of the RING1B C-terminal region upon binding the polycomb
      cbox domain.
AB  - Polycomb group (PcG) proteins are required for maintaining cell identity and stem
      cell self-renewal. RING1B and Polycomb (Pc) are two components of a multiprotein
      complex called polycomb repression complex 1 (PRC1) that is essential for
      establishing and maintaining long-term repressed gene states. Here we
      characterize the interaction between the C-terminal region of RING1B (C-RING1B)
      and the Pc cbox domain. The C-RING1B-cbox interaction displays a 1:1
      stoichiometry with dissociation constants ranging from 9.2 to 180 nM for the
      different Pc orthologues. NMR analysis of C-RING1B alone reveals line broadening.
      However, when it is in complex with the cbox domain, there is a striking change
      to the NMR spectrum indicative of conformational tightening. This conformational
      change may arise from the organization of the C-RING1B subdomains. The C-terminal
      regions of all PcG RING1 proteins are composed of two stretches of conserved
      sequences separated by a variable linker sequence. While the entire C-RING1B
      region is required for cbox binding, the N- and C-terminal halves of C-RING1B can
      be separated and are able to interact, suggesting the presence of an
      intramolecular interaction within C-RING1B. The flexibility within the C-RING1B
      structure allowing transitions between the intramolecular bound and unbound
      states may cause the broadened peaks of the C-RING1B NMR spectrum. Binding the
      cbox domain stabilizes C-RING1B, whereby broadening is eliminated. The presence
      of flexible regions could allow C-RING1B to bind a variety of different factors,
      ultimately recruiting RING1B and its associated PcG proteins to different genomic
      loci.

PMID- 18616294
TI  - Mutational specificity of gamma-radiation-induced guanine-thymine and thymine
      guanine intrastrand cross-links in mammalian cells and translesion synthesis past
      the guanine-thymine lesion by human DNA polymerase eta.
AB  - Comparative mutagenesis of gamma- or X-ray-induced tandem DNA lesions G[8,5-Me]T
      and T[5-Me,8]G intrastrand cross-links was investigated in simian (COS-7) and
      human embryonic (293T) kidney cells. For G[8,5-Me]T in 293T cells, 5.8% of
      progeny contained targeted base substitutions, whereas 10.0% showed semitargeted
      single-base substitutions. Of the targeted mutations, the G --> T mutation
      occurred with the highest frequency. The semitargeted mutations were detected up
      to two bases 5' and three bases 3' to the cross-link. The most prevalent
      semitargeted mutation was a C --> T transition immediately 5' to the G[8,5-Me]T
      cross-link. Frameshifts (4.6%) (mostly small deletions) and multiple-base
      substitutions (2.7%) also were detected. For the T[5-Me,8]G cross-link, a similar
      pattern of mutations was noted, but the mutational frequency was significantly
      higher than that of G[8,5-Me]T. Both targeted and semitargeted mutations occurred
      with a frequency of approximately 16%, and both included a dominant G --> T
      transversion. As in 293T cells, more than twice as many targeted mutations in COS
      cells occurred in T[5-Me,8]G (11.4%) as in G[8,5-Me]T (4.7%). Also, the level of
      semitargeted single-base substitutions 5' to the lesion was increased and 3' to
      the lesion decreased in T[5-Me,8]G relative to G[8,5-Me]T in COS cells. It
      appeared that the majority of the base substitutions at or near the cross-links
      resulted from incorporation of dAMP opposite the template base, in agreement with
      the so-called "A-rule". To determine if human polymerase eta (hpol eta) might be
      involved in the mutagenic bypass, an in vitro bypass study of G[8,5-Me]T in the
      same sequence was carried out, which showed that hpol eta can bypass the cross
      link incorporating the correct dNMP opposite each cross-linked base. For G[8,5
      Me]T, nucleotide incorporation by hpol eta was significantly different from that
      by yeast pol eta in that the latter was more error-prone opposite the cross
      linked Gua. The incorporation of the correct nucleotide, dAMP, by hpol eta
      opposite cross-linked T was 3-5-fold more efficient than that of a wrong
      nucleotide, whereas incorporation of dCMP opposite the cross-linked G was 10-fold
      more efficient than that with dTMP. Therefore, the nucleotide incorporation
      pattern by hpol eta was not consistent with the observed cellular mutations.
      Nevertheless, at and near the lesion, hpol eta was more error-prone compared to a
      control template. The in vitro data suggest that translesion synthesis by another
      Y-family DNA polymerase and/or flawed participation of an accessory protein is a
      more likely scenario in the mutagenesis of these lesions in mammalian cells.
      However, hpol eta may play a role in correct bypass of the cross-links.

PMID- 18616293
TI  - Subdividing repressor function: DNA binding affinity, selectivity, and allostery
      can be altered by amino acid substitution of nonconserved residues in a LacI/GalR
      homologue.
AB  - Many mutations that impact protein function occur at residues that do not
      directly contact ligand. To understand the functional contributions from the
      sequence that links the DNA-binding and regulatory domains of the LacI/GalR
      homologues, we have created a chimeric protein (LLhP), which comprises the LacI
      DNA-binding domain, the LacI linker, and the PurR regulatory domain. Although DNA
      binding site residues are identical in LLhP and LacI, thermodynamic measurements
      of DNA binding affinity show that LLhP does not discriminate between alternative
      DNA ligands as well as LacI. In addition, small-angle scattering experiments show
      that LLhP is more compact than LacI. When DNA is released, LacI shows a 20 A
      increase in length that was previously attributed to unfolding of the linker.
      This change is not seen in apo-LLhP, even though the linker sequences of the two
      proteins are identical. Together, results indicate that long-range functional and
      structural changes are propagated across the interface that forms between the
      linker and regulatory domain. These changes could be mediated via the side chains
      of several linker residues that contact the regulatory domains of the naturally
      occurring proteins, LacI and PurR. Substitution of these residues in LLhP leads
      to a range of functional effects. Four variants exhibit altered affinity for DNA,
      with no changes in selectivity or allosteric response. Another two result in
      proteins that bind operator DNA with very low affinity and no allosteric
      response, similar to LacI binding nonspecific DNA sequences. Two more
      substitutions simultaneously diminish affinity, enhance allostery, and profoundly
      alter DNA ligand selectivity. Thus, positions within the linker can be varied to
      modulate different aspects of repressor function.

PMID- 18616295
TI  - A second SARS-CoV S2 glycoprotein internal membrane-active peptide. Biophysical
      characterization and membrane interaction.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S)
      glycoprotein, a class I viral fusion protein, is responsible for the fusion
      between the membranes of the virus and the target cell. The S2 domain of protein
      S has been suggested to have two fusion peptides, one located at its N-terminus,
      downstream of the furin cleavage, and another, more internal, located immediately
      upstream of the HR1. Therefore, we have carried out a study of the binding and
      interaction with model membranes of a peptide corresponding to segment 873-888 of
      the SARS-CoV S glycoprotein, peptide SARS IFP, as well as the structural changes
      taking place in both the phospholipid and the peptide induced by the binding of
      the peptide to the membrane. We demonstrate that SARS IFP peptide binds to and
      interacts with phospholipid model membranes and shows a higher affinity for
      negatively charged phospholipids than for zwitterionic ones. SARS IFP peptide
      specifically decreases the mobility of the phospholipid acyl chains of negatively
      charged phospholipids and adopts different conformations in the membrane
      depending upon their composition. These data support its role in SARS-mediated
      membrane fusion and suggest that the regions where this peptide resides might
      assist the fusion peptide and/or the pretransmembrane segment of the SARS-CoV
      spike glycoprotein in the fusion process.

PMID- 18616296
TI  - Structure-immune response relationships of hapten-modified collagen II peptides
      in a T-cell model of allergic contact dermatitis.
AB  - Allergic contact dermatitis (ACD) is mediated by T cells that specifically
      recognize hapten-modified peptides. T cells are known to recognize antigens as
      short processed peptides bound to major histocompatibility complex (MHC)
      molecules on the surface of antigen-presenting cells (APC). It has previously
      been demonstrated that T cells can specifically recognize carbohydrates on the
      lysine at position 264 of the immunodominant (256-273) sequence from type II
      collagen (CII) and that such recognition is critical for the development of
      arthritis in mice and may play a role in rheumatoid arthritis in humans. In the
      present study, we have used this approach in modeling ACD, but instead of the
      carbohydrate, the strong sensitizer 2,4-dinitrofluorobenzene (DNFB) is bound to
      the epsilon-amine of the lysine at position 264. Specific T-cell hybridomas of
      this antigenic peptide, with dinitrophenyl (Dnp) on the epsilon-amine of lysine
      at position 264 (CIILysDnp 3), were established from mice immunized with
      CIILysDnp 3. In an immune response assay, these T-cell hybridomas were tested
      with a series of new synthetic hapten-modified peptides, all chemically identical
      except for the stereochemimistry (D, L) and the length of the position-264 amino
      acid side chain bonding the hapten. The T-cell hybridomas recognized the
      CIILysDnp 3 peptide used for immunization; interestingly, they also recognized
      the CII peptide with a one-carbon-longer side chain (homolysine), CIIhLysDnp 6,
      and CIIAlaPipDnp 11, having a ring structure analogous to that of lysine with the
      same number of carbons in the bonding chain as in the CIILysDnp 3 peptide used
      for immunization. Dnp-modified CII peptides with a shorter bonding chain produced
      no immune response. These data demonstrate that the T-cell recognition of the Dnp
      modified peptides is highly specific and moreover dependent on the length of the
      amino acid side chain that bonds the Dnp.

PMID- 18616297
TI  - Ceragenins: cholic acid-based mimics of antimicrobial peptides.
AB  - The prevalence of drug-resistant bacteria drives the quest for new
      antimicrobials, including those that are not expected to readily engender
      resistance. One option is to mimic Nature's most ubiquitous means of controlling
      bacterial growth, antimicrobial peptides, which have evolved over eons. In
      general, bacteria remain susceptible to these peptides. Human antimicrobial
      peptides play a central role in innate immunity, and deficiencies in these
      peptides have been tied to increased rates of infection. However, clinical use of
      antimicrobial peptides is hampered by issues of cost and stability. The
      development of nonpeptide mimics of antimicrobial peptides may provide the best
      of both worlds: a means of using the same mechanism chosen by Nature to control
      bacterial growth without the problems associated with peptide therapeutics. The
      ceragenins were developed to mimic the cationic, facially amphiphilic structures
      of most antimicrobial peptides. These compounds reproduce the required morphology
      using a bile-acid scaffolding and appended amine groups. The resulting compounds
      are actively bactericidal against both gram-positive and gram-negative organisms,
      including drug-resistant bacteria. This antimicrobial activity originates from
      selective association of the ceragenins with negatively charged bacterial
      membrane components. Association has been studied with synthetic models of
      bacterial membrane components, with bacterial lipopolysaccharide, with vesicles
      derived from bacterial phospholipids, and with whole cells. Comparisons of the
      antimicrobial activities of ceragenins and representative antimicrobial peptides
      suggest that these classes of compounds share a mechanism of action. Rapid
      membrane depolarization is caused by both classes as well as blebbing of
      bacterial membranes. Bacteria express the same genes in response to both classes
      of compounds. On the basis of the antibacterial activities of ceragenins and
      preliminary in vivo studies, we expect these compounds to find use in augmenting
      or replacing antimicrobial peptides in treating human disease.

PMID- 18616298
TI  - One-dimensional self-assembly of planar pi-conjugated molecules: adaptable
      building blocks for organic nanodevices.
AB  - In general, fabrication of well-defined organic nanowires or nanobelts with
      controllable size and morphology is not as advanced as for their inorganic
      counterparts. Whereas inorganic nanowires are widely exploited in optoelectronic
      nanodevices, there remains considerable untapped potential in the one-dimensional
      (1D) organic materials. This Account describes our recent progress and
      discoveries in the field of 1D self-assembly of planar pi-conjugated molecules
      and their application in various nanodevices including the optical and electrical
      sensors. The Account is aimed at providing new insights into how to combine
      elements of molecular design and engineering with materials fabrication to
      achieve properties and functions that are desirable for nanoscale optoelectronic
      applications. The goal of our research program is to advance the knowledge and
      develop a deeper understanding in the frontier area of 1D organic nanomaterials,
      for which several basic questions will be addressed: (1) How can one control and
      optimize the molecular arrangement by modifying the molecular structure? (2) What
      processing factors affect self-assembly and the final morphology of the
      fabricated nanomaterials; how can these factors be controlled to achieve the
      desired 1D nanomaterials, for example, nanowires or nanobelts? (3) How do the
      optoelectronic properties (e.g., emission, exciton migration, and charge
      transport) of the assembled materials depend on the molecular arrangement and the
      intermolecular interactions? (4) How can the inherent optoelectronic properties
      of the nanomaterials be correlated with applications in sensing, switching, and
      other types of optoelectronic devices? The results presented demonstrate the
      feasibility of controlling the morphology and molecular organization of 1D
      organic nanomaterials. Two types of molecules have been employed to explore the
      1D self-assembly and the application in optoelectronic sensing: one is perylene
      tetracarboxylic diimide (PTCDI, n-type) and the other is arylene ethynylene
      macrocycle (AEM, p-type). The materials described in this project are uniquely
      multifunctional, combining the properties of nanoporosity, efficient exciton
      migration and charge transport, and strong interfacial interaction with the guest
      (target) molecules. We see this combination as enabling a range of important
      technological applications that demand tightly coupled interaction between
      matter, photons, and charge. Such applications may include optical sensing,
      electrical sensing, and polarized emission. Particularly, the well-defined
      nanowires fabricated in this study represent unique systems for investigating the
      dimensional confinement of the optoelectronic properties of organic
      semiconductors, such as linearly polarized emission, dimensionally confined
      exciton migration, and optimal pi-electronic coupling (favorable for charge
      transport). Combination of these properties will make the 1D self-assembly ideal
      for many orientation-sensitive applications, such as polarized light-emitting
      diodes and flat panel displays.

PMID- 18616299
TI  - Gold supported on thin oxide films: from single atoms to nanoparticles.
AB  - [Figure: see text]. Historically, people have prized gold for its beauty and the
      durability that resulted from its chemical inertness. However, even the ancient
      Romans had noted that finely dispersed gold can give rise to particular optical
      phenomena. A decade ago, researchers found that highly dispersed gold supported
      on oxides exhibits high chemical activity in a number of reactions. These
      chemical and optical properties have recently prompted considerable interest in
      applications of nanodispersed gold. Despite their broad use, a microscopic
      understanding of these gold-metal oxide systems lags behind their application.
      Numerous studies are currently underway to understand why supported nanometer
      sized gold particles show catalytic activity and to explore possible applications
      of their optical properties in photonics and biology. This Account focuses on a
      microscopic understanding of the gold-substrate interaction and its impact on the
      properties of the adsorbed gold. Our strategy uses model systems in which gold
      atoms and clusters are supported on well-ordered thin oxide films grown on metal
      single crystals. As a result, we can investigate the systems with the rigor of
      modern surface science techniques while incorporating some of the complexity
      found in technological applications. We use a variety of different experimental
      methods, namely, scanning probe techniques (scanning tunneling microscopy and
      spectroscopy, STM and STS), as well as infrared (IR), temperature-programmed
      desorption (TPD), and electron paramagnetic resonance (EPR) spectroscopy, to
      evaluate these interactions and combine these results with theoretical
      calculations. We examined the properties of supported gold with increasing
      complexity starting from single gold atoms to one- and two-dimensional clusters
      and three-dimensional particles. These investigations show that the binding of
      gold on oxide surfaces depends on the properties of the oxide, which leads to
      different electronic properties of the Au deposits. Changes in the electronic
      structure, namely, the charge state of Au atoms and clusters, can be induced by
      surface defects such as color centers. Interestingly, the film thickness can also
      serve as a parameter to alter the properties of Au. Thin MgO films (two to three
      monolayer thickness) stabilize negatively charged Au atoms and two-dimensional Au
      particles. In three dimensions, the properties of Au particles bigger than 2-3 nm
      in diameter are largely independent of the support. Smaller three-dimensional
      particles, however, showed differences based on the supporting oxide. Presumably,
      the oxide support stabilizes particular atomic configurations, charge states, or
      electronic properties of the ultrasmall Au aggregates, which are in turn
      responsible for this distinct chemical behavior.

PMID- 18616300
TI  - Direct functionalization of nitrogen heterocycles via Rh-catalyzed C-H bond
      activation.
AB  - [Reaction: see text]. Nitrogen heterocycles are present in many compounds of
      enormous practical importance, ranging from pharmaceutical agents and biological
      probes to electroactive materials. Direct functionalization of nitrogen
      heterocycles through C-H bond activation constitutes a powerful means of
      regioselectively introducing a variety of substituents with diverse functional
      groups onto the heterocycle scaffold. Working together, our two groups have
      developed a family of Rh-catalyzed heterocycle alkylation and arylation reactions
      that are notable for their high level of functional-group compatibility. This
      Account describes our work in this area, emphasizing the relevant mechanistic
      insights that enabled synthetic advances and distinguished the resulting
      transformations from other methods. We initially discovered an intramolecular Rh
      catalyzed C-2 alkylation of azoles by alkenyl groups. That reaction provided
      access to a number of di-, tri-, and tetracyclic azole derivatives. We then
      developed conditions that exploited microwave heating to expedite these
      reactions. While investigating the mechanism of this transformation, we
      discovered that a novel substrate-derived Rh- N-heterocyclic carbene (NHC)
      complex was involved as an intermediate. We then synthesized analogous Rh-NHC
      complexes directly by treating precursors to the intermediate [RhCl(PCy 3)2] with
      N-methylbenzimidazole, 3-methyl-3,4-dihydroquinazoline, and 1-methyl-1,4
      benzodiazepine-2-one. Extensive kinetic analysis and DFT calculations supported a
      mechanism for carbene formation in which the catalytically active RhCl(PCy 3) 2
      fragment coordinates to the heterocycle before intramolecular activation of the C
      H bond occurs. The resulting Rh-H intermediate ultimately tautomerizes to the
      observed carbene complex. With this mechanistic information and the discovery
      that acid cocatalysts accelerate the alkylation, we developed conditions that
      efficiently and intermolecularly alkylate a variety of heterocycles, including
      azoles, azolines, dihydroquinazolines, pyridines, and quinolines, with a wide
      range of functionalized olefins. We demonstrated the utility of this methodology
      in the synthesis of natural products, drug candidates, and other biologically
      active molecules. In addition, we developed conditions to directly arylate these
      heterocycles with aryl halides. Our initial conditions that used PCy 3 as a
      ligand were successful only for aryl iodides. However, efforts designed to avoid
      catalyst decomposition led to the development of ligands based on 9
      phosphabicyclo[4.2.1]nonane (phoban) that also facilitated the coupling of aryl
      bromides. We then replicated the unique coordination environment, stability, and
      catalytic activity of this complex using the much simpler tetrahydrophosphepine
      ligands and developed conditions that coupled aryl bromides bearing diverse
      functional groups without the use of a glovebox or purified reagents. With
      further mechanistic inquiry, we anticipate that researchers will better
      understand the details of the aforementioned Rh-catalyzed C-H bond
      functionalization reactions, resulting in the design of more efficient and robust
      catalysts, expanded substrate scope, and new transformations.

PMID- 18616301
TI  - Fulvic acid sorption on muscovite mica as a function of pH and time using in situ
      X-ray reflectivity.
AB  - Interfacial structures of the basal surface of muscovite mica in 100 mg kg (-1)
      Elliott Soil Fulvic Acid II solutions were investigated using in situ X-ray
      reflectivity. Molecular-scale variations in the thickness and internal structure
      of the fulvic acid (FA) film were observed and quantified as a function of pH (2
      12) and reaction time (3-500 h at pH 3.7). At pH < or =6, the electron-density
      profile of the FA layer sorbed on the muscovite surface was composed of one near
      surface peak followed by a broad peak that diminished in electron density with
      distance from the surface. The presence of the near-surface peak is attributed to
      condensation of FA molecules during sorption. The apparent thickness of the FA
      layer decreased from 12.3 to 7.2 to 6.4 A as pH increased from 2 to 3.7 to 6,
      respectively. At pH > or =8.5, a distinct interfacial structure was observed,
      consisting of sharper peaks similar to those previously observed for muscovite in
      the absence of FA. These peaks are most likely composed of smaller aqueous
      species, such as H 2O molecules, metal ion impurities from FA, and Na (+) from
      NaOH. The FA sorbed on the muscovite surface at pH 3.7 maintained a relatively
      constant thickness after 3 hours. However, the electron density of the near
      surface FA peak increased by about 24% from 3 to 12 hours, and remained
      relatively constant from 12 to 500 hours. The electron density of the more
      distant part of the sorbed FA layer increased slightly after 12-50 hours of
      reaction but then decreased, and the broad peak flattened by 500 hours. Internal
      structural changes are possibly due to the slow sorption rate of FA molecules, or
      a fractionation effect, i.e., continuous subsitution of smaller FA molecules by
      larger FA molecules.

PMID- 18616302
TI  - Increasing efficiency of photoelectronic conversion by encapsulation of
      photosynthetic reaction center proteins in arrayed carbon nanotube electrode.
AB  - The construction of efficient light energy converting (photovoltaic and
      photoelectronic) devices is a current and great challenge in science and
      technology and one that will have important economic consequences. Here we show
      that the efficiency of these devices can be improved by the utilization of a new
      type of nano-organized material having photosynthetic reaction center proteins
      encapsulated inside carbon nanotube arrayed electrodes. In this work, a
      generically engineered bacterial photosynthetic reaction center protein with
      specifically synthesized organic molecular linkers were encapsulated inside
      carbon nanotubes and bound to the inner tube walls in unidirectional orientation.
      The results show that the photosynthetic proteins encapsulated inside carbon
      nanotubes are photochemically active and exhibit considerable improvement in the
      rate of electron transfer and the photocurrent density compared to the material
      constructed from the same components in traditional lamella configuration.

PMID- 18616303
TI  - A biomimetic alternative to poly(ethylene glycol) as an antifouling coating:
      resistance to nonspecific protein adsorption of poly(L-lysine)-graft-dextran.
AB  - Poly( L-lysine)- graft-dextran (PLL- g-dex), graft copolymers with dextran side
      chains grafted onto a poly( L-lysine) backbone, previously shown to be effective
      as stabilizers of DNA triple helices and as carriers of functional genes to
      target cells or tissues, were employed in this work to prevent nonspecific
      adsorption of proteins, as determined by means of optical waveguide lightmode
      spectroscopy. PLL- g-dex copolymers readily adsorb from aqueous solution onto
      negatively charged oxide surfaces and significantly reduce nonspecific protein
      adsorption onto bare silica-titania surfaces. While effective and equivalent
      surface adsorption and antifouling properties were observed for PLL- g-dex
      copolymers in a variety of architectures, nanotribological analysis by atomic
      force microscopy was able to distinguish between the different brush densities
      produced.

PMID- 18616305
TI  - Inkjet-printed thiol self-assembled monolayer structures on gold: quality control
      and microarray electrode fabrication.
AB  - Laterally structured, self-assembled monolayers (SAMs) of different thiols (HS-R
      X, R = (CH 2) 3-16, X = -CH 3, -COOH, -NH 2) on gold have been prepared by inkjet
      printing. The printer is a modified, low-cost desktop printer (Epson Stylus Photo
      R200), the ink is a 1 mM solution of the thiol in ethanol/glycerol (6:1). The
      quality of inkjet-printed large area SAMs obtained in this study is between that
      of a layer self-assembled from a thiol solution and that obtained by soft
      lithography, according to cyclic voltammetry, electrochemical impedance
      spectroscopy, scanning electrochemical microscopy (SECM), and polarization
      modulated Fourier transform infrared reflection-absorption spectroscopy (PM
      IRRAS). For the first time, simultaneous printing of two different thiols in a
      single print job as an alternative to sequential printing and backfilling is
      demonstrated. The smallest structures consisting of conductive disks of 40 microm
      diameter were analyzed as single spots by SECM and as random array electrodes
      with different average disk-disk distance. Conductive band electrodes with
      variable bandwidth (300 microm to 1 cm) are presented, as well as a pH switchable
      band structure. As compared to stamping, inkjet printing allows for simultaneous
      multiple thiol printing in a single print job with the resolution limited only by
      the droplet size and the precision of the translation stage.

PMID- 18616307
TI  - Enhancement at the junction of silver nanorods.
AB  - The enhancement of surface enhanced Raman scattering (SERS) at the junction of
      linearly joined silver nanorods (31 nm in diameter) deposited in the pores of
      anodic aluminum oxide templates was studied systematically by excitation with a
      632.8 nm laser line. The single and joined silver nanorod arrays showed a similar
      extinction spectrum when their length was the same. Maximum enhancement was
      observed from the junction system of two nanorods of the same size with a total
      length of 62 nm. This length also corresponded to the optimum length of single
      nanorods for SERS by excitation with a 632.8 nm laser line. The enhancement at
      the junction was approximately 40 times higher than that of the 31 nm single
      nanorod, while it was 4 times higher than that of the 62 nm single nanorod. The
      enhancement factor at the junction after oxide removal was approximately 3.9 x 10
      (9).

PMID- 18616306
TI  - Probing molecular-level surface structures of polyethersulfone/pluronic F127
      blends using sum-frequency generation vibrational spectroscopy.
AB  - We blended Pluronic F127 into polyethersulfone (PES) to improve surface
      properties of PES, which has been extensively used in biomaterial and other
      applications. The molecular surface structures of PES/Pluronic F127 blends have
      been investigated by sum-frequency generation (SFG) vibrational spectroscopy. The
      molecular orientation of surface functional groups of PES changed significantly
      when blended with a small amount of Pluornic F127. Pluronic F127 on the blend
      surface also exhibited different features upon contacting with water. The
      entanglement of PES chains with Pluronic F127 molecules rendered the blends with
      long-term surface stability in water in contrast to the situation where a layer
      of Pluronic F127 adsorbed on the PES surface. Atomic force microscopy (AFM) and
      quartz crystal microbalance (QCM) measurements were included to determine the
      relative amount of protein that adsorbed to the blend surfaces. The results
      showed a decreased protein adsorption amount with increasing Pluronic F127 bulk
      concentration. The correlations between polymer surface properties and detailed
      molecular structures obtained by SFG would provide insight into the designing and
      developing of biomedical polymers and functional membranes with improved fouling
      resistant properties.

PMID- 18616308
TI  - Interrogating interfacial organization in planar bilayer structures.
AB  - The field of biomimetic planar lipid membranes is finding increased importance as
      the need to devise sensing systems for biologically important species increases.
      We approach this area with an eye toward understanding how to interrogate local
      organization in these complex media. Our primary tools for this purpose are
      spectroscopy and electrochemistry, where imbedded reporter molecules serve as the
      information transducers. We use Langmuir-Blodgett (LB) and Langmuir-Schaefer (LS)
      methods to construct planar lipid membranes on hydrophilic solid substrates (Au
      for electrochemistry, SiO x for spectroscopy). Pyrene tethered to the substrate
      acts as our probe and AC voltammetry was used to evaluate its redox kinetics,
      showing slow, distance independent electron transfer between the pyrene moieties
      and the electrode for both monolayer and bilayer systems. Time-resolved
      fluorescence data indicate that tethered pyrene resides in a highly rigid
      environment and that the addition of the top lipid leaflet improves the
      organization of the bottom lipid leaflet. These data point to the cooperative
      effect of the bilayer leaflets in creating a system that is comparatively rigid
      on short length scales, and capable of mediating motion and accessibility of
      imbedded species.

PMID- 18616310
TI  - Silica passivation efficiency monitored by a surface-bound fluorescent dye.
AB  - A new method for evaluating surface passivation of silicon surfaces using a
      strongly adsorbing and fluorescing perylenediimide (PDI) dye is reported. Silanes
      containing differing reactive groups delivering a trimethylsilyl moiety were
      investigated for their ability to passivate glass surfaces, both from solution
      and in the vapor phase, as a function of temperature and concentration. Among the
      silanizing agents used in this study were 1,1,1,3,3,3-hexamethyldisilazane (
      HMDS), allyltrimethylsilane ( TMS-A), chlorotrimethylsilane ( TMS-Cl), N
      (trimethylsilyl)imidazole ( TMS-Im), and N, N-dimethylaminotrimethylsilane ( TMS
      DMA). Surface coverage was determined using fluorescence intensity. The highest
      surface coverage films were obtained on glass treated with HMDS vapor at 280
      degrees C or with solutions of TMS-Im or TMS-DMA at 105 degrees C. These studies
      provide important insight into the optimal methods for surface passivation.

PMID- 18616309
TI  - Assembly of dithiocarbamate-anchored monolayers on gold surfaces in aqueous
      solutions.
AB  - Dithiocarbamates (DTCs) can be formed by the in situ condensation of polar
      alkylamines with CS 2, and assembled into dithiocarbamate-anchored monolayers
      (DAMs) on Au substrates in aqueous solutions. Primary and secondary amines can
      both be used to prepare DTCs, but have significant differences in their
      reactivities and product stabilities. Ultraviolet absorption spectroscopy
      provides a convenient method for monitoring in situ DTC formation as well as the
      formation of potential byproducts. The kinetics of DAM assembly on Au substrates
      as measured by second harmonic generation (SHG) indicated first-order rate
      processes and saturation coverages similar to those of alkanethiols on Au.
      However, the rate of adsorption did not change with DTC concentration in a manner
      expected of Langmuir kinetics, and is attributed to the competitive adsorption of
      alkylammonium counterions to the freshly oxidized Au substrate. These analyses
      establish a practical range of conditions for preparing DAMs from polar amines
      using in situ DTC formation.

PMID- 18616311
TI  - Measuring the time-dependent functional activity of adsorbed fibrinogen by atomic
      force microscopy.
AB  - In this work, we measured time-dependent functional changes in adsorbed
      fibrinogen by measuring antigen-antibody debonding forces with atomic force
      microscopy (AFM). AFM probes were functionalized with monoclonal antibodies
      recognizing fibrinogen gamma 392-411, which includes the platelet binding
      dodecapeptide region. These probes were used to collect force measurements
      between the antibody and fibrinogen on mica substrates and the probability of
      antigen recognition was calculated. Statistical analysis showed that the
      probability of antibody-antigen recognition peaked at approximately 45 min
      postadsorption and decreased with increasing residence time. Macroscale platelet
      adhesion measurements on these mica substrates were determined to be greatest at
      fibrinogen residence times of approximately 45 min, which correlated well with
      the functional activity of adsorbed fibrinogen as measured by the modified AFM
      probes. These results demonstrate the utility of this approach for measuring
      protein function at or near the molecular scale and offers new opportunities for
      improved insights into the molecular basis for the biological response to
      biomaterials.

PMID- 18616313
TI  - Synthesis and gene transfection efficacies of PEI-cholesterol-based lipopolymers.
AB  - Nine lipopolymers based on low molecular weight polyethyleneimines (PEI) and
      cholesterol via an ether linkage between the polymer amine and the cholesterol
      backbone have been synthesized. Different percentage of cholesterol moieties have
      been grafted on three types of PEI of molecular weights 800, 1200, and 2000.
      These lipopolymers were studied for gene transfection activities in HeLa cells.
      All the lipopolymers were first optimized for enhanced transfection efficacies as
      coliposomes with DOPE. All lipopolymers are better transfecting agents and highly
      serum compatible than commercially available PEI-25KDa. Transfection efficacies
      and serum compatibility of lipopolymers were found to be dependent upon the MW of
      PEI used for lipopolymer synthesis and percentage of cholesterol grafting on
      lipopolymers. Cell viability assay showed that PEI-25KDa is highly toxic as
      compared to all the lipopolymers. Lipopolyplexes were characterized by
      transmission electron microscopy, which showed the presence of spherical
      aggregates.

PMID- 18616312
TI  - Synthesis of high aspect ratio quantum-size CdS nanorods and their surface
      dependent photoluminescence.
AB  - Colloidal CdS nanorods with diameters near 4 nm and narrow size distributions (
      approximately +/-10%) were synthesized up to 300 nm long by a sequential reactant
      injection technique that utilizes phosophonic acids as capping ligands. The
      phosphonic acid strongly passivates the nonpolar CdS surfaces and sequential
      reactant injection provides controlled CdS formation kinetics to enable
      heterogeneous and facet-selective CdS deposition on the more reactive {002}
      surfaces. With this process, the nanorod length can be systematically increased
      by increasing reactant addition to extend nanorod growth. The phosphonic acid
      concentration, however, is quite important, as "low" concentrations allow radial
      deposition and branching to occur. These high aspect ratio (>100) CdS nanorods
      luminesce with relatively high efficiencies of 10.8% quantum yield at room
      temperature. The luminescence, however, mostly arises from trap-related
      recombination, and the emission is significantly red-shifted from the absorption
      edge. Various surface passivation treatments were explored to eliminate trap
      emission and increase the luminescence quantum yield. Thiol and amine passivation
      both significantly reduced trap emission and enhanced band-edge emission, but the
      total luminescence quantum yields dropped significantly, with a maximum measured
      value of 1.5% for the amine-passivated CdS nanorods.

PMID- 18616314
TI  - Computer simulations of the refolding of sperm whale apomyoglobin from high
      temperature denaturated state.
AB  - The refolding mechanism of apomyoglobin (apoMb) subsequent to high-temperature
      unfolding has been examined using computer simulations with atomic level detail.
      The folding of this protein has been extensively studied experimentally,
      providing a large database of folding parameters which can be probed using
      simulations. In the present study, 4-folding trajectories of apoMb were computed
      starting from coiled structures. A crystal structure of sperm whale myoglobin
      taken from the Protein Data Bank was used to construct the final native
      conformation by removal of the heme group followed by energy optimization. The
      initial unfolded conformations were obtained from high-temperature molecular
      dynamics simulations. Room-temperature refolding trajectories at neutral pH were
      obtained using the stochastic difference equation in length algorithm. The
      folding trajectories were compared with experimental results and two previous
      molecular dynamics studies at low pH. In contrast to the previous simulations, an
      extended intermediate with large helical content was not observed. In the present
      study, a structural collapse occurs without formation of helices or native
      contacts. Once the protein structure is more compact (radius of gyration<18 A)
      secondary and tertiary structures appear. These results suggest that apoMb
      follows a different folding pathway after high-temperature denaturation.

PMID- 18616315
TI  - Effect of the air-water interface on the structure of lysozyme in the presence of
      guanidinium chloride.
AB  - We report observations of the changes in the surface structure of lysozyme
      adsorbed at the air-water interface produced by the chemical denaturant
      guanidinium chloride. A primary result is the durability of the adsorbed surface
      layer to denaturation, as compared to the molecule in the bulk solution. Data on
      the surface film were obtained from X-ray and neutron reflectivity measurements
      and modeled simultaneously. The behavior of lysozyme in G.HCl solutions was
      determined by small-angle X-ray scattering. For the air-water interface,
      determination of the adsorbed protein layer dimensions shows that at low to
      moderate denaturant concentrations (up to 2 mol L(-1)), there is no significant
      distortion of the protein's tertiary structure at the interface, as changes in
      the orientation of the protein are sufficient to model data. At higher denaturant
      concentrations, time-dependent multilayer formation occurred, indicating
      molecular aggregation at the surface. Methodologies to predict the protein
      orientation at the interface, based on amino acid residues' surface affinities
      and charge, were critiqued and validated against our experimental data.

PMID- 18616316
TI  - pH-dependent behaviors of electroactive myoglobin loaded into layer-by-layer
      films assembled with alginate and hydroxyethyl cellulose ethoxylate.
AB  - In the present work, strong polybase quaternized hydroxyethyl cellulose
      ethoxylate (HECE) and weak polyacid alginate (AA) were assembled into {HECE/AA} n
      layer-by-layer (LBL) films on electrodes by electrostatic interaction between
      them, and the films were then immersed in myoglobin (Mb) solution to load Mb into
      the films, designated as {HECE/AA}n-Mb. The {HECE/AA}n-Mb films showed a nearly
      reversible cyclic voltammetric (CV) peak pair at about -0.34 V vs SCE in pH 7.0
      buffers for Mb heme Fe(III)/Fe(II) redox couple, and the surface concentration of
      electroactive Mb in the films (Gamma*) was affected significantly by the pH of Mb
      loading solution and testing solution. The amount of Mb loaded from pH 5.0
      solution was much larger than that from pH 9.0 solution, which is mainly
      attributed to the higher degree of swelling, porosity, and permeability of
      {HECE/AA}n films at pH 5.0 than at pH 9.0. In addition, the electrostatic
      interaction between Mb and the AA component in the films might also play an
      important role in Mb loading. The pH of the testing solution where {HECE/AA}n-Mb
      films were tested by CV also influenced the Gamma* value, showing that the
      fraction of electroactive Mb among the total Mb loaded into the films increased
      remarkably as the pH of the testing solution decreased. This result is
      rationalized in terms of the pH-dependent film permeability toward counterions
      and the electron-hopping mechanism in electron transfer of redox proteins in the
      film phase. This model system may provide a general and effective approach to
      control the electroactivity of immobilized redox proteins in the multilayer
      assembly containing weak polyions by adjusting pH and may guide us to develop the
      new kind of controllable electrochemical biosensors based on the direct
      electrochemistry of enzymes.

PMID- 18616317
TI  - Structural analysis of bioengineered alpha-D-glucan produced by a triple mutant
      of the Glucansucrase GTF180 enzyme from Lactobacillus reuteri strain 180:
      generation of (alpha1-->4) linkages in a native (1-->3)(1-->6)-alpha-D-glucan.
AB  - Site-directed mutagenesis of the glucansucrase gtf180 gene from Lactobacillus
      reuteri strain 180 was used to transform the active site region. The alpha-D
      glucan ( mEPS-PNNS) produced by the triple mutant V1027P:S1137N:A1139S differed
      in structure from that of the wild-type alpha-D-glucan ( EPS180). Besides (alpha1
      ->3) and (alpha1-->6) linkages, as present in EPS180, mEPS-PNNS also contained
      (alpha1-->4) linkages. Linkage analysis, periodate oxidation, and 1D/2D (1)H NMR
      spectroscopy of the intact mEPS-PNNS, as well as MS and NMR analysis of
      oligosaccharides obtained by partial acid hydrolysis of mEPS-PNNS afforded a
      composite model, which includes all identified structural features.

PMID- 18616318
TI  - Aromatic nitration in liquid Ag0.51K0.42Na0.07NO3.
AB  - Aromatic molecules have a strong affinity for silver(I) and dissolve to a limited
      extent in Ag 0.51K 0.42Na 0.07NO 3, a low-melting eutectic mixture of silver,
      potassium, and sodium nitrates. Aromatic nitration in this inorganic ionic liquid
      leads to products which arise from nonelectrophilic substitution pathways.

PMID- 18616319
TI  - Convenient synthesis of 3-alkoxy-3-aryloxindoles by intramolecular arylation of
      mandelic amides.
AB  - Medicinally important 3-alkoxy-3-aryloxindoles are conveniently prepared by the
      rapid microwave-promoted palladium-catalyzed intramolecular enolate arylation of
      mandelate-derived anilides.

PMID- 18616320
TI  - Enantioselective BINOL-phosphoric acid catalyzed Pictet-Spengler reactions of N
      benzyltryptamine.
AB  - Optically active tetrahydro-beta-carbolines were synthesized via an ( R)-BINOL
      phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction of N
      benzyltryptamine with a series of aromatic and aliphatic aldehydes. The
      tetrahydro-beta-carbolines were obtained in yields ranging from 77% to 97% and
      with ee values up to 87%. The triphenylsilyl-substituted BINOL-phosphoric acid
      proved to be the catalyst of choice for the reaction with aromatic aldehydes. For
      the aliphatic aldehydes, 3,5-bistrifluoromethylphenyl-substituted BINOL
      phosphoric acid was identified as the best catalyst.

PMID- 18616321
TI  - Studies on the mechanism of allylic coupling reactions: a hammett analysis of the
      coupling of aryl silicate derivatives.
AB  - Hammett analysis of the palladium-catalyzed allyl-aryl coupling reaction has
      demonstrated that the rate of the coupling reaction is enhanced by electron
      withdrawing groups on the aryl siloxane. The positive slope of the Hammett plot
      indicated involvement of a charged transition state in which negative charge on
      the aryl ring is stabilized inductively. This result is consistent with either
      transmetalation or reductive elimination being the rate-determining step in the
      coupling process. Furthermore, the influence of ligand on the metal site has been
      assessed from competition studies as a function of ligand type, cone angle, and
      electronic effects. From the relative ratios of coupling products produced in the
      Hammett study, it is possible to gather insight into the role of the electronic
      as well as the steric effects of ligands on the mechanism of the coupling
      reaction.

PMID- 18616322
TI  - 1,5-Asymmetric induction in boron-mediated aldol reactions of beta-alkoxy
      methylketones.
AB  - Good levels of substrate-controlled, 1,5- syn-stereoinduction are obtained in
      boron-mediated aldol reactions of beta-trichloromethyl-beta-alkoxy and beta
      trifluoromethyl-beta-alkoxy methylketones with achiral aldehydes, independent of
      the nature of the beta-alkoxy protecting group (TBS or PMB). In the case of boron
      aldol reactions of beta-aryl-beta-alkoxy methylketones, the 1,5- anti-adducts
      were obtained with high levels of diastereoselectivity only with a beta-OPMB
      group.

PMID- 18616323
TI  - CuH-catalyzed reactions.

PMID- 18616324
TI  - Ag-mediated reactions: coupling and heterocyclization reactions.

PMID- 18616325
TI  - Spin-dependent tunneling transport into CrO2 nanorod devices with nonmagnetic
      contacts.
AB  - Single-crystal nanorods of half-metallic chromium dioxide (CrO2) were synthesized
      and structurally characterized. Spin-dependent electrical transport was
      investigated in individual CrO2 nanorod devices contacted with nonmagnetic
      metallic electrodes. Negative magnetoresistance (MR) was observed at low
      temperatures due to the spin-dependent direct tunneling through the contact
      barrier and the high spin polarization in the half-metallic nanorods. The
      magnitude of this negative magnetoresistance decreases with increasing bias
      voltage and temperature due to spin-independent inelastic hopping through the
      barrier, and a small positive magnetoresistance was found at room temperature. It
      is believed that the contact barrier and the surface state of the nanorods have
      great influence on the spin-dependent transport limiting the magnitude of MR
      effect in this first attempt at spin filter devices of CrO2 nanorods with
      nonmagnetic contacts.

PMID- 18616326
TI  - In-situ TEM observation of repeating events of nucleation in epitaxial growth of
      nano CoSi2 in nanowires of Si.
AB  - The formation of CoSi and CoSi2 in Si nanowires at 700 and 800 degrees C,
      respectively, by point contact reactions between nanodots of Co and nanowires of
      Si have been investigated in situ in a ultrahigh vacuum high-resolution
      transmission electron microscope. The CoSi2 has undergone an axial epitaxial
      growth in the Si nanowire and a stepwise growth mode was found. We observed that
      the stepwise growth occurs repeatedly in the form of an atomic step sweeping
      across the CoSi2/Si interface. It appears that the growth of a new step or a new
      silicide layer requires an independent event of nucleation. We are able to
      resolve the nucleation stage and the growth stage of each layer of the epitaxial
      growth in video images. In the nucleation stage, the incubation period is
      measured, which is much longer than the period needed to grow the layer across
      the silicide/Si interface. So the epitaxial growth consists of a repeating
      nucleation and a rapid stepwise growth across the epitaxial interface. This is a
      general behavior of epitaxial growth in nanowires. The axial heterostructure of
      CoSi2/Si/CoSi2 with sharp epitaxial interfaces has been obtained. A discussion of
      the kinetics of supply limited and source-limited reaction in nanowire case by
      point contact reaction is given. The heterostructures are promising as high
      performance transistors based on intrinsic Si nanowires.

PMID- 18616327
TI  - Facile synthesis of bimetallic nanoplates consisting of Pd cores and Pt shells
      through seeded epitaxial growth.
AB  - Pd-Pt core-shell nanoplates with hexagonal and triangular shapes were synthesized
      through the heterogeneous, epitaxial growth of Pt on Pd nanoplates. The Pd
      nanoplates were synthesized by reducing Na2PdCl4 precursor with PVP as a reducing
      agent, which then served as seeds for the nucleation of Pt atoms formed by
      reducing H2PtCl6 with citric acid. Characterization of the as-prepared Pd-Pt
      nanoplates by scanning transmission electron microscopy and high-resolution
      transmission electron microscopy reveals that a thin, uniform Pt shell was formed
      around the Pd nanoplate, demonstrating the layer-by-layer epitaxial growth of Pt
      on Pd surface in this approach. The close lattice match between Pd and Pt
      (lattice mismatch of only 0.77%) and the slow reduction rate associated with the
      mild reducing power of citric acid play key roles in achieving the epitaxial
      growth of Pt shells on Pd nanoplates.

PMID- 18616328
TI  - Polarization driven covalently-bonded octahedral-twinning and backbone-peripheral
      helical nanoarchitectures.
AB  - We report the novel superstructural chiral polar-surface induced backbone
      peripheral-helical (BPH) hierarchical architecture of zincblende SiC made
      possible by precise helical epitaxy. We show by direct image that this
      architecture has the mother-daughter relationship. The center of the BPH consists
      of periodic octahedral modular units with chiral sidewalls. By forming Si-C
      covalent bonds at the sidewalls, a daughter SiC wire spontaneously vine-grows in
      a peripherally helical way on the mother wire. All of the information of the
      mother wire, including twinning, polarity and even stacking fault, are completely
      copied and inherited by the daughter wire one-by-one at the atomic level. Our
      findings thus provide a simple growth method and the necessary atomistic
      mechanism for novel polar surface driven superstructural twinning and subsequent
      BPH growth, which should be universal for zincblende semiconductors and even
      could be true for other noncentral-symmetric compounds.

PMID- 18616329
TI  - Nanomechanical assay to investigate the selectivity of binding interactions
      between volatile benzene derivatives.
AB  - Understanding the interactions between aromatic gas molecules and various simple
      aromatic receptor molecules is important in developing selective receptors for
      volatile organic compounds (VOCs). Here, five benzene thiols with different
      functional end groups were used to investigate the weak binding of aromatic
      vapors such as dinitrotolouene (DNT) and toluene. A multiplexed microcantilever
      array in conjunction with a very low concentration vapor generation system was
      developed to study multiple receptor-target interactions simultaneously.
      Differential nanomechanical responses of such devices provided insight into the
      influence of various chemical and structural features of such molecules.

PMID- 18616330
TI  - Coalescence and interface diffusion in linear CdTe/CdSe/CdTe heterojunction
      nanorods.
AB  - Colloidal nanorods with linear CdTe/CdSe/CdTe heterojunctions were synthesized by
      sequential reactant injection. After CdTe deposition at the ends of initially
      formed CdSe nanorods, continued heating in solution leads to Se-Te interdiffusion
      across the heterojunctions and coalescence to decreased aspect ratio. The Se-Te
      interdiffusion rates were measured by mapping the composition profile using
      nanobeam energy dispersive X-ray spectroscopy (EDS) along the lengths of
      individual nanorods aged in hot solvent for different amounts of time. The rate
      of nanorod coalescence was also measured and compared to model predictions using
      a continuum viscous flow model, which appears to provide a reasonable estimate of
      the coalescence rate.

PMID- 18616331
TI  - Photophysics and nonlinear absorption of peripheral-substituted zinc
      phthalocyanines.
AB  - The photophysical properties, such as the UV-vis absorption spectra, triplet
      transient difference absorption spectra, triplet excited-state extinction
      coefficients, quantum yields of the triplet excited state, and lifetimes of the
      triplet excited state, of 10 novel zinc phthalocyanine derivatives with mono- or
      tetraperipheral substituents have been systematically investigated in DMSO
      solution. All these complexes exhibit a wide optical window in the visible
      spectral range and display long triplet excited-state lifetimes (140-240 mus). It
      has been found that the complexes with tetrasubstituents at the alpha-positions
      exhibit a bathochromic shift in their UV-vis absorption spectra, fluorescence
      spectra, and triplet transient difference absorption spectra and have larger
      triplet excited-state absorption coefficients. The nonlinear absorption of these
      complexes has been investigated using the Z-scan technique. It is revealed that
      all complexes exhibit a strong reverse saturable absorption at 532 nm for
      nanosecond and picosecond laser pulses. The excited-state absorption cross
      sections were determined through a theoretical fitting of the experimental data
      using a five-band model. The complexes with tetrasubstituents at the alpha
      positions exhibit larger ratios of triplet excited-state absorption to ground
      state absorption cross sections (sigma T/sigma g) than the other complexes. In
      addition, the wavelength-dependent nonlinear absorption of these complexes was
      studied in the range of 470-550 nm with picosecond laser pulses. All complexes
      exhibit reverse saturable absorption in a broad visible spectral range for
      picosecond laser pulses. Finally, the nonlinear transmission behavior of these
      complexes for nanosecond laser pulses was demonstrated at 532 nm. All complexes,
      and especially the four alpha-tetrasubstituted complexes, exhibit stronger
      reverse saturable absorption than unsubstituted zinc phthalocyanines due to the
      larger ratio of their excited-state absorption cross sections to their respective
      ground-state absorption cross sections.

PMID- 18616332
TI  - The effect and influence of cis-ligands on the electronic and oxidizing
      properties of nonheme oxoiron biomimetics. A density functional study.
AB  - Density functional theory studies on the nature of the cis effect and cis
      influence of ligands on oxoiron nonheme complexes have been performed. A detailed
      analysis of the electronic and oxidizing properties of [Fe(IV)O(TPA)L](+) with L
      = F(-), Cl(-), and Br(-) and TPA = tris-(2-pyridylmethyl)amine are presented and
      compared with [Fe(IV)O(TPA)NCCH(3)](2+). The calculations show that the
      electronic cis effect is determined by favorable orbital overlap between first
      row elements with the metal, which are missing between the metal and second- and
      third-row elements. As a consequence, the metal 3d block is split into a one
      below-two set of orbitals with L = Cl(-) and Br(-), and the HOMO/LUMO energy gap
      is widened with respect to the system with L = F(-). However, this larger
      HOMO/LUMO gap does not lead to large differences in electron affinities of the
      complexes. Moreover, a quantum mechanical analysis of the binding of the ligand
      shows that it is built up from a large electric field effect of the ligand on the
      oxoiron species and a much smaller quantum mechanical effect due to orbital
      overlap. These contributions are of similar strength for the three tested halogen
      cis ligands and result in similar reactivity patterns with substrates. The
      calculations show that [Fe(IV)O(TPA)L](+) with L = F(-), Cl(-), and Br(-) have
      closely lying triplet and quintet spin states, but only the quintet spin state is
      reactive with substrates. Therefore, the efficiency of the oxidant will be
      determined by the triplet-quintet spin state crossing of the reaction. The
      reaction of styrene with a doubly charged reactant, that is, [Fe(V)O(TPA)L](2+)
      with L = F(-), Cl(-), and Br(-) or [Fe(V)O(TPA)NCCH(3)](3+), leads to an initial
      electron transfer from the substrate to the metal followed by a highly exothermic
      epoxidation mechanism. These reactivity differences are mainly determined by the
      overall charge of the system rather than the nature of the cis ligand.

PMID- 18616333
TI  - Thermodynamics and biological properties of the aqueous solutions of new
      glucocationic surfactants.
AB  - Thermodynamic properties of aqueous solutions of newly synthesized compounds,
      namely, N-[2-(beta-D-glucopyranosyl)ethyl]-N,N-dimethyl-N-alkylammonium bromides
      with hydrophobic tails of 12 (C12DGCB) and 16 (C16DGCB) carbon atoms, determined
      as a function of concentration by means of direct methods, are reported here.
      Dilution enthalpies, densities, and sound velocities were measured at 298 K,
      allowing for the determination of apparent and partial molar enthalpies, volumes,
      and compressibilities. Changes in thermodynamic quantities upon micellization
      were derived using a pseudophase-transition approach. From a comparison with the
      corresponding acetylated compounds N-[2-(2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranosyl)ethyl]-N,N-dimethyl-N-dodecylammonium bromide (C12AGCB) and N-[2
      (2,3,4,6-tetra-O-acetyl-beta-D-glucopyanosyl)ethyl]-N,N-dimethyl-N
      hexadecylammonium bromide (C16AGCB), the role played in the micellization process
      by the acetylated glycosyl moiety was inferred: it enhances the hydrophobic
      character of the molecule and lowers the change in enthalpy of micelle formation
      by about 1.5 kJ mol(-1). By comparing the volume of C12DGCB with those of DEDAB
      and DTAB, the volumes taken up by the (beta- d-glucopyranosyl)ethyl and beta- d
      glucopyranosyl groups were found to be 133 and 99 cm3 mol(-1), respectively.
      Regarding the interaction with DPPC membranes, it seems that the sugar moiety of
      the hexadecyl deacetylated compound gives rise to hydrogen bonds with the oxygen
      atoms of the lipid phosphates, shifting the phase transition of DPPC from a
      bilayer gel to a bilayer liquid crystal to lower temperatures. C16AGCB induces
      significantly greater changes than C16DGCB in the structure of liposomes,
      suggesting the formation of domains. The interaction is strongly enhanced by the
      presence of water. Neither compound interacts strongly with DNA or compacts it,
      as shown by EMSA assays and AFM images. Only C16AGCB is able to deliver little
      DNA inside cells when coformulated with DOPE, as shown by the transient
      transfection assay. This might be related to the ability of C16AGCB to form
      surfactant-rich domains in the lipid structure.

PMID- 18616334
TI  - Electromagnetic functionalized cage-like polyaniline composite nanostructures.
AB  - Novel cage-like and electromagnetic functional polyaniline (PANI)/CoFe2O4
      composite nanostructures, in which the self-assembled PANI nanofibers
      (approximately 15 nm in diameter) entwined around the octahedral CoFe2O4 magnet
      acting as the nucleation site or template, were successfully prepared by FeCl3 as
      either oxidant and dopant via a self-assembly process. The coordination effect of
      the magnet as a nucleation site or template and the magnetic interaction between
      the PANI nanofibers and CoFe2O4 as a driving force results in such cage-like
      nanostructures. The cage-like composite nanostructures not only have high
      conductivity (sigmamax approximately 5.2 S/cm), but also show a typical
      ferromagnetic behavior.

PMID- 18616335
TI  - A new case of induced helical chirality in a bichromophoric system: absolute
      configuration of transparent and flexible diols from the analysis of the
      electronic circular dichroism spectra of the corresponding di(1-naphthyl)ketals.
AB  - Di(1-naphthyl)ketals of 1, n-diols show couplet effects allied to the (1)B
      naphthalene transition in their CD spectra. This means that they assume a
      conformation with a prevailing sense of twist of the naphthalene rings, imposed
      by the absolute configuration (AC) of the starting diols and by the nature of the
      R 1 groups. A positive couplet for aliphatic diols is a probe of ( R, R), AC
      while the opposite sign is found for ( R, R) aromatic diols.

PMID- 18616336
TI  - Electronic modulation of fused oligothiophenes by chemical oxidation.
AB  - The reaction of pentathienoacene (f-5T) with mCPBA produced a series of oxidized
      derivatives containing one or two thiophene- S, S-dioxide rings. The
      regioselectivity of the oxidation reflects the aromaticity of each thiophene ring
      in the f-5T skeleton, and the extent of the oxidation significantly affects the
      fluorescence and redox properties.

PMID- 18616337
TI  - Protecting group free glycosidations using p-toluenesulfonohydrazide donors.
AB  - N'-Glycopyranosylsulfonohydrazides are introduced as glycosyl donors for
      protecting group free synthesis of O-glycosides, glycosyl azides, and oxazolines.
      Mono- and disaccharides containing a reducing terminal N-acetylglucosamine
      residue were condensed with p-toluenesulfonylhydrazide to give the desired beta-
      d-pyranose donors. These donors can be activated with NBS and then glycosidated
      with the desired alcohol or transformed to the oxazoline or glycosyl azide.

PMID- 18616338
TI  - A new H2O2/acid anhydride system for the iodoarene-catalyzed C-C bond-forming
      reactions of phenols.
AB  - We have succeeded in the first versatile iodoarene-catalyzed C-C bond-forming
      reactions by development of a new reoxidation system at low temperatures using
      stoichiometric bis(trifluoroacetyl) peroxide A in 2,2,2-trifluoroethanol (TFE).
      The catalytic system supplies a wide range of substrates and functional
      availabilities sufficient to be used in the key synthetic process of producing
      biologically important Amaryllidaceae alkaloids.

PMID- 18616339
TI  - Control of four stereocenters in an organocatalytic domino double Michael
      reaction: efficient synthesis of multisubstituted cyclopentanes.
AB  - A highly enantioselective and diastereoselective domino organocatalytic double
      Michael reaction which provides expedited access to multifunctionalized five
      membered rings catalyzed by 9-amino-9-deoxyepiquinine (V) has been developed.
      Simple operational procedures, high yields (81-92%), excellent enantioselectivity
      (90-97% ee), diastereoselectivities (95:5->99:1 dr), and immense potential of
      synthetic versatility of the products render this new methodology highly
      appealing for asymmetric synthesis.

PMID- 18616340
TI  - Synthesis, electronic properties, and X-ray structural characterization of
      tetrarylbenzo[1,2-b:4,5-b']difuran cation radicals.
AB  - Electroactive tetraarylbenzo[1,2- b:4,5- b']difuran (BDF) and model
      diarylbenzofuran derivatives are synthesized and their structures are established
      by X-ray crystallography. Isolation and X-ray crystallographic characterization
      of the robust cation-radical salts of BDF derivatives confirm that a single
      charge in the BDFs is stabilized largely by the benzodifuran and coplanar alpha
      aryl groups lying on the longitudinal axis. These findings suggest that the
      linear arrays of BDFs may allow the construction of molecular wires suitable for
      long-range electron transport.

PMID- 18616341
TI  - A concise total synthesis of largazole, solution structure, and some preliminary
      structure activity relationships.
AB  - A total synthesis of largazole that proceeds in 8 steps from commercial materials
      is reported, along with some structure-activity relationships. A combination of
      NMR studies and molecular modeling have also provided a preliminary picture of
      the conformation of largazole.

PMID- 18616343
TI  - New MCR-Heck-isomerization cascade toward indoles.
AB  - The use of ortho-iodonitrophenol in Ugi-Smiles reaction coupled with Heck
      cyclization gives new access to indole scaffolds. The sequence can be performed
      in a one-pot reaction if the residual isocyanide is neutralized prior to the
      addition of the palladium catalyst.

PMID- 18616342
TI  - Concise synthesis of indole-fused 1,4-diazepines through copper(I)-catalyzed
      domino three-component coupling-cyclization-N-arylation under microwave
      irradiation.
AB  - Indole-fused benzo-1,4-diazepines were synthesized by copper-catalyzed domino
      three-component coupling-indole formation- N-arylation under microwave
      irradiation from a simple N-mesyl-2-ethynylaniline. This method was also
      applicable to the formation of heterocycle-fused 1,4-diazepines.

PMID- 18616344
TI  - Fluorescent sensing of IP3 with a Trifurcate Zn(II)-containing chemosensing
      ensemble system.
AB  - A trifurcate receptor containing Zn(II)-dipicolylamine ligands is developed for
      the fluorescent sensing of IP 3, myo-inositol 1,4,5-tris(phosphate), through an
      indicator displacement approach. The chemosensing ensemble containing the Zn(II)
      complex and eosin Y as indicator shows the maximum fluorescence restoration for
      IP 3 among various other anions including phosphate derivatives in water buffered
      at pH = 7.

PMID- 18616345
TI  - Nanodiscs for immobilization of lipid bilayers and membrane receptors: kinetic
      analysis of cholera toxin binding to a glycolipid receptor.
AB  - Nanodiscs are self-assembled soluble discoidal phospholipids bilayers
      encirculated by an amphipathic protein that together provide a functional
      stabilized membrane disk for the incorporation of membrane-bound and membrane
      associated molecules. The scope of the present work is to investigate how
      nanodiscs and their incorporated membrane receptors can be attached to surface
      plasmon resonance sensorchips and used to measure the kinetics of the interaction
      between soluble molecules and membrane receptors inserted in the bilayer of
      nanodiscs. Cholera toxin and its glycolipid receptor G(M1) constitute a system
      that can be considered a paradigm for interactions of soluble proteins with
      membrane receptors. In this work, we have investigated different technologies for
      capturing nanodiscs containing the glycolipid receptor G(M1) in lipid bilayers,
      enabling measurements of binding of its soluble interaction partner cholera toxin
      B subunit to the receptor with the sensorchip-based surface plasmon resonance
      (SPR) technology. The measured stoichiometric and kinetic values of the
      interaction are in agreement with those reported by previous studies, thus
      providing proof-of-principle that nanodiscs can be employed for kinetic SPR
      studies.

PMID- 18616346
TI  - SDS-PAGE of proteins using a chameleon-type of fluorescent prestain.
AB  - A new prestaining method for protein SDS-PAGE was developed using the fluorogenic
      amino-reactive label Py-1. This resulted in one of the fastest, most sensitive,
      and environmentally friendly protocols available. It is mainly due to the unique
      optical properties of Py-1, which is blue and virtually nonfluorescent but turns
      to red and becomes much more strongly fluorescent once it is conjugated to the
      amino group of a protein. Staining times of 30 min are adequate to visualize
      subnanogram quantities of proteins because pre-electrophoretic labeling Py-1 does
      not require the time-consuming steps of washing or fixation of gels. LODs as low
      as 16 pg of protein are found which is better than the best (commercial)
      poststains and comparable to the best (commercial) prestains. In addition,
      prestaining requires marginal amounts of staining solution. The change in
      electrophoretic mobility and band broadening is at a low level because Py-1
      causes a mass shift of 288 Da per bound molecule only. By virtue of the small
      mass shift it causes, this stain is compatible with mass spectrometric protein
      analysis even though it acts as a covalent label.

PMID- 18616347
TI  - Detection and relative quantification of siRNA double strands by MALDI mass
      spectrometry.
AB  - While MALDI-MS is widely accepted for quality control of synthetic
      oligonucleotides, this method has been regarded as not applicable for a control
      of the purity and correct annealing of double strands. The results presented here
      show that the double-strand intensities measured by MALDI-MS maintain and reflect
      the solution conditions. Using a single-stranded RNA as internal standard, the
      double-strand intensity can be determined by measuring the intensity ratio of the
      single strands to the standard under "native" conditions and after denaturation
      with formic acid. For siRNAs with fully matched 20-21 base pairs, relative
      intensities of the double strands are between 94 and 97.2%. The stability
      determined by MALDI-MS for different RNA duplexes correlates well with calculated
      T m values and the content of G-C pairs. Furthermore, the quantification method
      enables one to determine an excess of one single strand and the contribution of
      duplex formation by truncated strands. The results show that MALDI-MS is a fast
      and reliable method for quality control of synthetic siRNA.

PMID- 18616348
TI  - A combinatorial H4 tail library for exploring the histone code.
AB  - Histone modifications modulate chromatin structure and function. A
      posttranslational modification-randomized, combinatorial library based on the
      first 21 residues of histone H4 was designed for systematic examination of
      proteins that interpret a histone code. The 800-member library represented all
      permutations of most known modifications within the N-terminal tail of histone
      H4. To determine its utility in a protein binding assay, the on-bead library was
      screened with an antibody directed against phosphoserine 1 of H4. Among the hits,
      59 of 60 sequences were phosphorylated at S1, while 30 of 30 of those selected
      from the nonhits were unphosphorylated. A 512-member version of the library was
      then used to determine the binding specificity of the double tudor domain of
      hJMJD2A, a histone demethylase involved in transcriptional repression. Global
      linear least-squares fitting of modifications from the identified peptides (40
      hits and 34 nonhits) indicated that methylation of K20 was the primary
      determinant for binding, but that phosphorylation and acetylation of neighboring
      sites attenuated the interaction. To validate the on-bead screen, isothermal
      titration calorimetry was performed with 13 H4 peptides. Dissociation constants
      ranged from 1 mM to 1 microM and corroborated the screening results. The general
      approach should be useful for probing the specificity of any histone-binding
      protein.

PMID- 18616349
TI  - Input-dependent wave propagations in asymmetric cellular automata: possible
      behaviors of feed-forward loop in biological reaction network.
AB  - Dynamical aspects of the asymmetric cellular automata were investigated to
      consider the signaling processes in biological systems. As a meta-model of the
      cascade of feed-forward loop type network motifs in biological reaction networks,
      we consider the one dimensional asymmetric cellular automata where the state of
      each cell is controlled by a trio of cells, the cell itself, the nearest upstream
      cell and the next nearest upstream cell. Through the systematic simulations, some
      novel input-dependent wave propagations were found in certain asymmetric CA,
      which may be useful for the signaling processes like the distinction, the
      filtering and the memory of external stimuli.

PMID- 18616350
TI  - The effect of patterns of infectiousness on epidemic size.
AB  - In the course of an infectious disease in a population, each infected individual
      presents a different pattern of progress through the disease, producing a
      corresponding pattern of infectiousness. We postulate a stochastic infectiousness
      process for each individual with an almost surely finite integral, or total
      infectiousness. Individuals also have different contact rates. We show that the
      distribution of the final epidemic size depends only on the contact rates and the
      integrated infectiousness. As a particular case, zero infectiousness on an
      initial time interval corresponds to a period of latency, which does not affect
      the final epidemic size in general stochastic and deterministic epidemic models,
      as is well known from the literature.

PMID- 18616351
TI  - Existence of multiple-stable equilibria for a multi-drug-resistant model of
      Mycobacterium tuberculosis.
AB  - The resurgence of multi-drug-resistant tuberculosis in some parts of Europe and
      North America calls for a mathematical study to assess the impact of the
      emergence and spread of such strain on the global effort to effectively control
      the burden of tuberculosis. This paper presents a deterministic compartmental
      model for the transmission dynamics of two strains of tuberculosis, a drug
      sensitive (wild) one and a multi-drug-resistant strain. The model allows for the
      assessment of the treatment of people infected with the wild strain. The
      qualitative analysis of the model reveals the following. The model has a disease
      free equilibrium, which is locally asymptotically stable if a certain threshold,
      known as the effective reproduction number, is less than unity. Further, the
      model undergoes a backward bifurcation, where the disease-free equilibrium
      coexists with a stable endemic equilibrium. One of the main novelties of this
      study is the numerical illustration of tri-stable equilibria, where the disease
      free equilibrium coexists with two stable endemic equilibrium when the
      aforementioned threshold is less than unity, and a bi-stable setup, involving two
      stable endemic equilibria, when the effective reproduction number is greater than
      one. This, to our knowledge, is the first time such dynamical features have been
      observed in TB dynamics. Finally, it is shown that the backward bifurcation
      phenomenon in this model arises due to the exogenous re-infection property of
      tuberculosis.

PMID- 18616352
TI  - Mathematical analysis of a HIV model with frequency dependence and viral
      diversity.
AB  - We consider the effect of viral diversity on the human immune system with the
      frequency dependent proliferation rate of CTLs and the elimination rate of
      infected cells by CTLs. The model has very complex mathematical structures such
      as limit cycle, quasi-periodic attractors, chaotic attractors, and so on. To
      understand the complexity we investigate the global behavior of the model and
      demonstrate the existence and stability conditions of the equilibria. Further we
      give some theoretical considerations obtained by our mathematical model to HIV
      infection.

PMID- 18616353
TI  - Permanence for two-species Lotka-Volterra cooperative systems with delays.
AB  - In this paper, a two-species Lotka-Volterra cooperative delay system is
      considered, and the relationships between the delays and the permanence are
      obtained. Some sufficient conditions for the permanence under the assumption of
      smallness of the delays are obtained. Two examples are given to illustrate the
      theorems.

PMID- 18616354
TI  - Modelling the immunopathogenesis of HIV-1 infection and the effect of multidrug
      therapy: the role of fusion inhibitors in HAART.
AB  - There is currently tremendous effort being directed at developing potent, highly
      active antiretroviral therapies that can effectively control HIV- 1 infection
      without the need for continuous, lifelong use of these drugs. In the ongoing
      search for powerful antiretroviral agents that can affect sustained control for
      HIV infection, mathematical models can help in assessing both the correlates of
      protective immunity and the clinical role of a given drug regimen as well as in
      understanding the efficacy of drug therapies administered at different stages of
      the disease. In this study, we develop a new mathematical model of the immuno
      pathogenesis of HIV-1 infection, which we use to assess virological responses to
      both intracellular and extracellular antiretroviral drugs. We first develop a
      basic mathematical model of the immuno-pathogenesis of HIV-1 infection that
      incorporates three distinct stages in the infection cycle of HIV-1: entry of HIV
      1 into the cytoplasm of CD4+ T cells, transcription of HIV-1 RNA to DNA within
      CD4+ T cells, and production of HIV-1 viral particles within CD4+ T cells. Then
      we extend the basic model to incorporate the effect of three major categories of
      anti-HIV-1 drugs: fusion/entry inhibitors (FIs), reverse transcriptase inhibitors
      (RTIs), and protease inhibitors (PIs). Model analysis establishes that the actual
      drug efficacy of FIs, gamma and of PIs, kappa is the same as their effective
      efficacies while the effective drug efficacy for the RTIs, gamma (upsilon ) , is
      dependent on the rate of transcription of the HIV-1 RNA to DNA, and the lifespan
      of infected CD4+ T cells where virions have only entered the cytoplasm and that
      this effective efficacy is less than the actual efficacy, upsilon. Our studies
      suggest that, of the three anti-HIV drug categories (FIs, RTIs, and PIs), any
      drug combination of two drugs that includes RTIs is the weakest in the control of
      HIV-1 infection.

PMID- 18616355
TI  - A deterministic model of schistosomiasis with spatial structure.
AB  - It has been observed in several settings that schistosomiasis is less prevalent
      in segments of river with fast current than in those with slow current. Some
      believe that this can be attributed to flush-away of intermediate host snails.
      However, free-swimming parasite larvae are very active in searching for suitable
      hosts, which indicates that the flush-away of larvae may also be very important.
      In this paper, the authors establish a model with spatial structure that
      characterizes the density change of parasites following the flush-away of larvae.
      It is shown that the reproductive number, which is an indicator of prevalence of
      parasitism, is a decreasing function of the river current velocity. Moreover,
      numerical simulations suggest that the mean parasite load is low when the
      velocity of river current flow is sufficiently high.

PMID- 18616356
TI  - Modeling the rapid spread of avian influenza (H5N1) in India.
AB  - Controlling the spread of avian bird flu has become a challenging tasks for
      Indian agriculture and health administrators. After the first evidence and
      control of the virus in 2006, the virus attacked five states by January 2008.
      Based on the evidence of rapid spread of the avian bird flu type H5N1 among the
      Indian states of Maharashtra, Manipur, and West Bengal, and in the partially
      affected states of Gujarat and Madhya Pradesh, a model is developed to understand
      the spread of the virus among birds and the effect of control measures on the
      dynamics of its spread. We predict that, in the absence of control measures, the
      total number of infected birds in West Bengal within ten and twenty days after
      initial discovery of infection were 780,000 and 2.1 million, respectively. When
      interventions are introduced, these values would have ranged from 65,000 to
      225,000 after ten days and from 16,000 to 190,000 after twenty days. We show that
      the farm and market birds constitute the major proportion of total infected
      birds, followed by domestic birds and wild birds in West Bengal, where a severe
      epidemic hit recently. Culling 600,000 birds in ten days might have reduced the
      current epidemic before it spread extensively. Further studies on appropriate
      transmission parameters, contact rates of birds, population sizes of poultry and
      farms are helpful for planning.

PMID- 18616357
TI  - Biological control of the chemostat with nonmonotonic response and different
      removal rates.
AB  - We show the global stabilization of the chemostat with nonmonotonic growth,
      adding a new species as a "biological" control, in presence of different removal
      rates for each species. This result is obtained by an extension of the
      Competitive Exclusion Principle in the chemostat, for the case of two species
      with different removal rates and at least one nonmonotonic response.

PMID- 18616358
TI  - An extension of the Beretta-Kuang model of viral diseases.
AB  - A model for the complete life cycle of marine viruses is presented. The Beretta
      Kuang model introduces an explicit equation for viral particles but the
      replication process of viral particles in their hosts is not considered. The
      extended model keeps the structure of the original model. This makes it possible
      to estimate the growth parameters of the viruses for a given parametrisation of
      the Beretta-Kuang model.

PMID- 18616359
TI  - Stabilization due to predator interference: comparison of different analysis
      approaches.
AB  - We study the influence of the particular form of the functional response in two
      dimensional predator-prey models with respect to the stability of the nontrivial
      equilibrium. This equilibrium is stable between its appearance at a transcritical
      bifurcation and its destabilization at a Hopf bifurcation, giving rise to
      periodic behavior. Based on local bifurcation analysis, we introduce a
      classification of stabilizing effects. The classical Rosenzweig-MacArthur model
      can be classified as weakly stabilizing, undergoing the paradox of enrichment,
      while the well known Beddington-DeAngelis model can be classified as strongly
      stabilizing. Under certain conditions we obtain a complete stabilization,
      resulting in an avoidance of limit cycles. Both models, in their conventional
      formulation, are compared to a generalized, steady-state independent two
      dimensional version of these models, based on a previously developed
      normalization method. We show explicitly how conventional and generalized models
      are related and how to interpret the results from the rather abstract stability
      analysis of generalized models.

PMID- 18616360
TI  - Calculation of R0 for age-of-infection models.
AB  - We consider age-of-infection epidemic models to describe multiple- stage epidemic
      models, including treatment. We derive an expression for the basic reproduction
      number R0 in terms of the distributions of periods of stay in the various
      compartments. We find that, in the model without treatment, R0 depends only on
      the mean periods in compartments, and not on the form of the distributions. In
      treatment models, R0 depends on the form of the distributions of stay in
      infective compartments from which members are removed for treatment, but the
      dependence for treatment compartments is only on the mean stay in the
      compartments. The results give a considerable simplification in the calculation
      of the basic reproduction number.

PMID- 18616361
TI  - Folate and clefts of the lip and palate--a U.K.-based case-control study: Part I:
      Dietary and supplemental folate.
AB  - OBJECTIVES: We sought to determine the associations between nonsyndromic cleft
      lip with or without cleft palate (CL-P) and cleft palate only (CP) and maternal
      intake of dietary folate and supplemental folic acid, in an area where the
      prevalence at birth of neural tube defects has been high and flour is not
      fortified with folic acid. METHODS: Interviews regarding periconceptional dietary
      intake and supplement use were completed with the mothers of 112 CL-P cases, 78
      CP cases, and 248 unaffected infants. The data were analyzed by logistic
      regression methods. RESULTS: There was no overall association between CL-P and CP
      and either energy-adjusted total folate intake or supplemental folic acid use,
      irrespective of dosage. CONCLUSION: Overall, higher intakes of total folate do
      not appear to prevent oral clefts in this population.

PMID- 18616362
TI  - Folate and clefts of the lip and palate--a U.K.-based case-control study: Part
      II: Biochemical and genetic analysis.
AB  - OBJECTIVE: To investigate associations between nonsyndromic oral clefts and
      biochemical measures of folate status and the MTHFR C677T variant in the United
      Kingdom, where there has been no folic acid fortification program. METHOD:
      Dietary details were obtained from the mothers of 112 cases of cleft lip with or
      without cleft palate (CL+/-P), 78 cleft palate only (CP) cases, and 248
      unaffected infants. Infant and parental MTHFR C677T genotype was determined. Red
      blood cell (RBC) and serum folate and homocysteine levels were assessed in 12
      month postpartum blood samples from a subset of mothers. The data were analyzed
      by logistic and log-linear regression methods. RESULTS: There was an inverse
      association between CL+/-P and maternal MTHFR CT (odds ratio [OR] = 0.5, 95%
      confidence interval [CI] = 0.31-0.95) and TT (OR = 0.6, 95% CI = 0.21-1.50)
      genotypes, with similar risk estimates for CP. There was no clear association
      with infant MTHFR genotype. Higher levels of maternal postpartum RBC and serum
      folate were associated with a lower risk for CL+/-P and an increased risk for CP.
      Higher levels of serum homocysteine were associated with a slightly increased
      risk for both CL+/-P and CP. CONCLUSION: While the inverse relation between the
      mother's having the MTHFR C677T variant and both CL+/-P and CP suggests
      perturbation of maternal folate metabolism is of etiological importance,
      contrasting relations between maternal postpartum levels of RBC and serum folate
      by type of cleft are difficult to explain.

PMID- 18616363
TI  - Clicks produced as compensatory articulations in two adolescents with
      velocardiofacial syndrome.
AB  - OBJECTIVE: To report perceptual and dynamic articulatory electropalatography data
      on clicks produced as compensatory articulations by two adolescents (S1 and S2)
      with velocardiofacial syndrome and velopharyngeal dysfunction. RESULTS: The
      perceptual analysis showed that both speakers produced click substitutions for
      English targets /t/, /d/, /k/, /g/, and S2 additionally produced clicks for /p/,
      /b/, and /tintegral/, //. The adolescents produced a range of clicks, which
      varied in placement (bilabial, dental, alveolar, palatal), voicing (voiced,
      voiceless), and nasality (nasal, nonnasal). Measurements from the
      electropalatography data for lingual clicks revealed two articulatory closures,
      one in the anterior and another in the posterior region of the hard palate. The
      data revealed how the two closures were timed precisely to produce the click
      sound. The clicks involved a complex and highly coordinated sequence of tongue
      maneuvers similar to clicks in some southern African languages. CONCLUSIONS:
      Clicks are interpreted as compensatory articulations enabling some speakers with
      velopharyngeal dysfunction to produce plosive and affricate sounds with
      perceptually salient acoustic bursts in the oral cavity. Clicks as compensatory
      articulations merit further systematic investigation, and the procedures reported
      in this study are considered appropriate for such research.

PMID- 18616364
TI  - A comparison of Shepard's osteotome versus trapdoor flap technique to harvest
      iliac crest bone for secondary alveolar bone grafting.
AB  - OBJECTIVE: To compare the postoperative donor site morbidity and alveolar bone
      graft results following two different techniques for iliac crest bone graft
      harvest: a closed (Shepard's osteotome) and an open (trapdoor flap) technique.
      DESIGN: A retrospective review of two cohorts of alveolar bone grafts performed
      from 1998 to 2004 in Birmingham Children's Hospital by two surgeons using
      different harvest techniques. Medical and nursing anesthetic notes and medication
      charts were reviewed. Alveolar bone graft results were assessed using
      preoperative and postoperative radiographic studies. PATIENTS: A total of 137
      patients underwent an operation. Of these, 109 patients were compatible with the
      inclusion criteria (data available, first operation, no multiple comorbidities).
      Sixty-four patients had iliac bone harvested using the open trapdoor technique,
      while 45 had the same procedure using the closed osteotomy technique. RESULTS:
      Maximum bone graft volumes harvested were similar with both techniques. The mean
      length of hospital stay was 50.9 hours for the osteotome and 75.5 hours for the
      open technique group (p < .0001). The postoperative analgesia requirement was
      higher and the postoperative mobilization was delayed and more difficult for the
      open technique patients (p < .0005). Kindelan scores performed by two independent
      orthodontists were similar for both techniques. CONCLUSION: The findings
      demonstrate that harvesting bone from the iliac crest using an osteotome
      technique reduces time in hospital, analgesia requirements, and postoperative
      donor site morbidity with no detrimental outcome.

PMID- 18616365
TI  - Long-term effects of pharyngeal flaps on the upper airways of subjects with
      velopharyngeal insufficiency.
AB  - OBJECTIVES: To investigate the long-term effects of pharyngeal flap surgery (PFS)
      on nasal and nasopharyngeal dimensions of patients with velopharyngeal
      insufficiency (VPI) and to correlate the findings with the onset of respiratory
      complaints after surgery. DESIGN/PARTICIPANTS: Prospective study in 58
      nonsyndromic patients with repaired cleft palate and VPI, evaluated 2 days before
      and 5 months (POST1) and 1 year (POST2) after PFS, on average. Patients were
      divided into two groups: one consisting of patients with postoperative
      respiratory complaints (RC group) and the other without complaints (NRC group).
      INTERVENTIONS: Superiorly based PFS. MAIN OUTCOME MEASURES: Respiratory
      complaints (self reports of mouth breathing, snoring, and other sleep obstructive
      events) assessed at POST1 and POST2, and minimum nasal (NCSA) and nasopharyngeal
      (NPA) cross-sectional areas assessed by rhinomanometry at POST2. RESULTS:
      Respiratory complaints were reported by 55% and 36% of the patients evaluated at
      POST1 and POST2, respectively. Posterior rhinomanometry showed a significant
      postoperative reduction of mean NCSA in the RC and NRC groups (p < .05), to
      subnormal levels in some of them. The decrease was more pronounced in the RC
      group. No significant changes in NCSA were observed by anterior rhinomanometry.
      Similar results were obtained when NPA was assessed by modified anterior
      rhinomanometry. CONCLUSION: In the long-term, PFS yielded a significant reduction
      in upper airways dimensions beyond what should be expected and associated with
      persistent respiratory complaints in some cases.

PMID- 18616366
TI  - Midface osteotomy versus distraction: the effect on speech, nasality, and
      velopharyngeal function in craniofacial dysostosis.
AB  - OBJECTIVE: To assess speech outcomes following midface advancement and to explore
      whether the type of advancement surgery affects speech differently in patients
      with craniofacial dysostosis. DESIGN: Prospective, before-after group design.
      SUBJECTS: Fifteen consecutive patients were included in the study. Eight
      underwent advancement by osteotomy and seven by distraction. All patients were
      seen preoperatively and at least once postoperatively. MAIN OUTCOME MEASURES:
      Percentage of consonants correct, nature and type of articulation errors,
      nasalance score, severity ratings of resonance and of velopharyngeal function
      using nasendoscopy and lateral videofluoroscopy, and amount of forward
      advancement. RESULTS: No statistically significant differences were found between
      groups for pre- and postoperative changes of percentage of consonants correct (p
      = .755, median difference 3.0, 95% confidence interval for median difference [
      14.22, 20.22]) and nasalance (p = .171, median difference = -12.00, 95%
      confidence interval for median differences [-30.46, 6.46]). There was no
      statistically significant correlation between amount of forward advancement and
      nasalance (r = .87, p = .799) and percentage of consonants correct (r = -.550, p
      = .064). Findings from lateral videofluoroscopy and nasendoscopy are described.
      Individual changes of speech outcomes are reported. CONCLUSIONS: In view of the
      small sample size, results need to be interpreted with caution. However, the
      study adds to current limited knowledge with this clinical group. Further
      research with bigger sample sizes and randomization of patients into the
      different surgical groups is warranted.

PMID- 18616367
TI  - Effect of infant orthopedics on facial appearance of toddlers with complete
      unilateral cleft lip and palate (Dutchcleft).
AB  - OBJECTIVE: To evaluate the effect of infant orthopedics (IO) on facial appearance
      of 54 patients with unilateral cleft lip and palate (UCLP), aged 4 and 6 years.
      DESIGN: Prospective two-arm randomized controlled clinical trial in three Cleft
      Palate Centers in the Netherlands (Dutchcleft-trial). INTERVENTIONS: Patients
      were divided randomly into two groups. Half of the patients (IO+) had a plate
      until surgical closure of the soft palate at the age of +/- 52 weeks; the other
      half (IO-) received no intervention. MAIN OUTCOME MEASURES: Facial appearance at
      4 and 6 years of age assessed on full face photographs and photographs showing
      only nose and mouth. Ratings were performed on a VAS-scale by professionals and
      laymen. RESULTS: At 4 years of age the full face pictures of IO+ children were
      scored to be more attractive than those of IO- children. However, this difference
      had disappeared at 6 years of age. At the age of 6, only professionals saw a
      significant difference on nasolabial photographs between IO+ and IO-. Regression
      analysis showed a minor effect of occlusion, lip revision, or type of nose
      reconstruction on the esthetic results. CONCLUSIONS: IO had a positive effect on
      full facial appearance of UCLP children at the age of 4 years, but at the age of
      6, only professionals saw a positive effect of IO on the nasolabial photographs.
      This is irrelevant for UCLP patients since they deal with laymen in their daily
      life.

PMID- 18616368
TI  - Anatomy and growth of the fetal soft palate: a cadaveric study to improve its
      ultrasonographic observation.
AB  - OBJECTIVE: To determine the anatomy of the soft and hard palate during fetal
      growth in order to improve its ultrasonographic prenatal visualization. DESIGN:
      Anatomic study in human formalin-fixed fetus. METHODS: The heads of 18 second and
      third trimester fetuses were studied in the median sagittal plan. Measurements of
      the soft palate, the velopharynx, the root of the tongue, and the oral floor were
      taken. The hard palate/soft palate angle and the anterior cranial base/soft
      palate angle were measured. RESULTS: The growth of the hard palate was linear,
      and the growth of the soft palate was polynomial (second order) during the period
      studied. The hard palate/soft palate angle was 150.33 degrees +/- 7.62 and 150.20
      degrees +/- 6.67 in the second and third trimester, respectively. The anterior
      position of the soft palate in relation to the anterior cranial base was 48.8
      degrees +/- 3.13 in the second trimester and 52.26 degrees +/- 3.31 in the third
      trimester. Its posterior position was 89.66 degrees +/- 5.51 in the second
      trimester and 92.97 degrees +/- 4.01 in the third trimester. Throughout the fetal
      period, the soft palate moved downward relative to the clivus and cervical spine.
      CONCLUSIONS: Despite the nonlinear growth and downward displacement of the soft
      palate during fetal life, its position remains stable. These results may be
      useful to explore the fetal soft palate using 2D and 3D ultrasonography and to
      improve the prenatal diagnosis of isolated cleft palate.

PMID- 18616369
TI  - Crossmodal temporal processing acuity in children with oral clefts.
AB  - OBJECTIVE: We have previously found that, in children with certain oral clefts,
      the rate of sequential information processing is significantly impaired in vision
      and tactile somatosensation but not so clearly in audition. Here, we studied
      crossmodal functions by investigating temporal processing acuity of cleft
      children with audiovisual, audiotactile, and visuotactile tasks. PARTICIPANTS:
      Temporal processing acuity was studied in 10-year-old children, 19 with cleft lip
      with or without cleft palate and 38 with cleft palate or submucous cleft palate.
      DESIGN: Children estimated whether brief stimuli of two concurrent three-stimulus
      sequences, each in a different modality, were simultaneous or not when the
      stimulus interval varied adaptively. The 8-millisecond stimuli were flashes in
      vision, tone bursts in audition, and solenoid touches of a finger in
      somatosensation. RESULTS: The group with cleft lip with or without cleft palate
      performed better than the group with cleft palate or submucous cleft palate in
      audiovisual temporal processing acuity, but the group's superiority was not
      statistically significant in audiotactile or visuotactile temporal processing
      acuity. CONCLUSIONS: Audiovisual crossmodal sequential information processing is
      probably impaired in some cleft children in the group with cleft palate or
      submucous cleft palate. Our results suggest further studies on the audiovisual
      capacities of children with cleft.

PMID- 18616370
TI  - Dental anomalies as part of the cleft spectrum.
AB  - OBJECTIVE: The aim of this study was to determine subphenotypes of clefts based
      on tooth development. Dental phenotypes (tooth agenesis, supernumerary and
      impacted teeth, transposition, and structural anomalies) outside the cleft area
      in the permanent dentition of oral cleft individuals were investigated. DESIGN:
      Evaluation of dental records of cleft patients. SETTING: National Museum of
      Health and Medicine, Washington, D.C. PATIENTS, PARTICIPANTS: A collection of
      dental casts, radiographic and clinical records of 146 patients with oral clefts
      was evaluated. MAIN OUTCOME MEASURE: Association of dental anomalies with
      preferential subtypes of clefts. RESULTS: Forty-seven individuals (32.19%)
      presented at least one dental anomaly outside the cleft area. Individuals with
      complete cleft lip and palate (CLP) presented more dental anomalies than
      individuals with incomplete CLP (p = .04). Cleft palate individuals presented
      more dental anomalies than CLP individuals (p = .048). Maxillary lateral incisors
      and premolars were the most affected teeth. High incidence of maxillary second
      premolar agenesis was observed in individuals with bilateral CLP (p = .04). In
      cases with unilateral CLP, 12.5% presented dental anomalies of the maxillary
      lateral incisors on the noncleft side. Cleft palate individuals presented a high
      incidence of mandibular premolar anomalies (p = .004). CONCLUSION: Future studies
      should consider the inclusion of a complete dental description to aid in the
      definition of cleft subphenotypes to be studied.

PMID- 18616371
TI  - Evaluation of the presence or absence of papilla between tooth and implant.
AB  - OBJECTIVE: The purpose of this study was to evaluate the papilla level adjacent
      to single-tooth implants in the maxillary anterior region in individuals with
      cleft lip, alveolus, and palate to verify whether there is correlation among the
      vertical distance, horizontal distance, dental/prosthetic crown shape, and
      periodontal/peri-implant biotype with the presence of interproximal papilla.
      DESIGN: Cross-sectional. SETTING: Hospital for Rehabilitation of Craniofacial
      Anomalies, University of Sao Paulo (HRAC/USP). PATIENTS: 77 papillae in 40
      patients. INTERVENTIONS: The periodontal/peri-implant biotype was clinically
      evaluated and characterized as thin or thick. Intraoral photographs were used to
      evaluate the presence or absence of papilla. MAIN OUTCOME MEASURES:
      Classification in scores (0 to 3) and determination of length (CL) and width (CW)
      of crowns adjacent to papillae. The CW/CL ratio was calculated for each crown in
      order to characterize it as square-shaped or triangular-shaped. The vertical and
      horizontal distances were obtained by radiographic evaluation. RESULTS: The
      correlations between vertical distance and papilla score and horizontal distance
      and papilla score were statistically significant (p = .02 and p = .01). There was
      no significant difference between crown shape and periodontal/peri-implant
      biotype in distinct correlations with the papilla score (p = .41 and p = .07).
      CONCLUSION: The results suggest that the vertical and horizontal distances may
      have independent or combined relationship with the existence of interproximal
      papilla; the periodontal/peri-implant biotype (phenotype) was not correlated with
      the presence or absence of papilla, as well as the shape of the dental/prosthetic
      crown.

PMID- 18616372
TI  - Maxillary segmental distraction in a patient with bilateral cleft lip and
      alveolus with subsequent tooth transplantation: a preliminary case report.
AB  - Segmental distraction osteogenesis in the maxillary alveolar process makes it
      possible to close alveolar clefts in patients with cleft lip and alveolus
      successfully. Dental spaces occurring in the lateral segment can subsequently be
      fully closed by transplanting teeth into this area. This new method of treatment
      is advantageous for patients with broad clefts and multiple missing teeth in the
      maxilla.

PMID- 18616373
TI  - Academic and clinical training in cleft palate for speech-language pathologists.
AB  - OBJECTIVE: The purpose of this study was to obtain information about academic and
      clinical training of speech-language pathology students in cleft palate (CP).
      METHODS: Representatives of 232 accredited graduate programs in speech-language
      pathology were invited via e-mail to complete a web-based 32-item questionnaire.
      Questions focused on the type and nature of courses offered related to CP,
      availability of clinical practica, and number of hours of clinical experience by
      students. An item-by-item analysis was conducted and descriptive statistics
      obtained. RESULTS: A total of 127 (54.7%) of the programs responded. Sixty-seven
      percent offered coursework exclusively devoted to CP, and for 53% of these it was
      a required course. For the programs that did not offer an exclusive course on CP,
      35% indicated that CP was covered in other courses such as articulation, voice,
      or anatomy and physiology. Fifty-four percent of the programs offered clinical
      practica in CP. For these, a median of five students of a median graduate speech
      language pathology class of 43 were enrolled in practica involving CP (range = 0
      21), and students spent a median of 2 hours in practica involving CP (range = 0
      100). CONCLUSIONS: Cleft palate is a complex disorder to which many students have
      limited exposure and for which more graduate training is unlikely since the 1993
      American Speech-Language-Hearing Association (ASHA) certification changes. As a
      result, there is a need to look towards alternative methods to enhance the
      educational and clinical experiences of students and practitioners in cleft
      palate.

PMID- 18616374
TI  - Henningsson G, Kuehn D, Sell D, Sweeney T, Trost-Cardamone J, Whitehill T.
      Universal parameters for reporting speech outcomes in individuals with cleft
      palate. Cleft Palate Craniofac J. 2008;45:1-17.

PMID- 18616377
TI  - Wastewater-contaminated groundwater as a source of endogenous hormones and
      pharmaceuticals to surface water ecosystems.
AB  - Increasing residential development in watershed recharge areas increases the
      likelihood of groundwater and surface water contamination by wastewater effluent,
      particularly where on-site sewage treatment is employed. This effluent contains a
      range of compounds including those that have been demonstrated to mimic or
      interfere with the function of natural hormones in aquatic organisms and humans.
      To explore whether groundwater contaminated by discharge from on-site septic
      systems affects water quality in surface water ecosystems, we measured steroidal
      hormones, pharmaceuticals, and other organic wastewater compounds (OWCs) in water
      collected from six aquifer-fed ponds in areas of higher and lower residential
      density on Cape Cod (Massachusetts, USA). We detected both a greater number and
      higher concentrations of OWCs in samples collected from ponds located in higher
      residential density areas. Most often detected were the steroidal hormones
      androstenedione, estrone, and progesterone and the pharmaceuticals carbamazepine,
      pentoxifylline, sulfamethoxazole, and trimethoprim. Of particular concern,
      estrogenic hormones were present at concentrations approaching those that induce
      physiological responses in fish. While a number of papers have reported on
      surface water contamination by OWCs from wastewater treatment plants, our results
      show that surface water ecosystems in unconfined aquifer settings are susceptible
      to contamination by estrogenic and other biologically active OWCs through
      recharge from aquifers contaminated by residential septic systems.

PMID- 18616378
TI  - Effects of bisphenol a on fecundity, egg hatchability, and juvenile growth of
      Marisa cornuarietis.
AB  - Recent work on the snail Marisa cornuarietis has claimed to show endocrine
      disruption in response to bisphenol A (BPA). The present experimental design was
      optimized to detect effects of BPA on fecundity, egg hatchability, and juvenile
      growth, with an emphasis on reproduction, since previous studies suggested this
      to be a sensitive endpoint. No differences in eggs/female/ month between
      unexposed snails and snails exposed to nominal concentrations of 0.1, 1, 25, and
      640 microg BPA/L during six months of exposure were found. No effect of BPA on
      the percentage of eggs hatching successfully was found, as was no difference in
      time to hatching between the control and any BPA treatment. We observed a
      significant decrease in female growth and a marginal effect on female wet weight
      in the 640-microg/L treatment compared to the control and a significant increase
      in male growth rate and a marginal increase in male wet weight in the 1-microg/L
      treatment compared to the control. However, a much greater proportion of the
      variability in juvenile growth was explained by variation between pairs and
      between siblings from the same pair than by BPA treatment. We conclude that
      effects of BPA in the nominal exposure range 0.1 to 640 microg/L (measured range
      0.062-696 microg/L) are unlikely to be of significance for field populations of
      this species. An additional adult fecundity trial at 22 degrees C (in contrast to
      all other experiments that were conducted at 25 degrees C) found no evidence to
      suggest that snails are more sensitive to BPA at the lower temperature, as has
      been previously claimed. The present results indicate that the sensitivity of M.
      cornuarietis to BPA is similar to that of other aquatic invertebrates for which
      data are available.

PMID- 18616379
TI  - First report of the introduction of an Australian temnocephalidan into the New
      World.
AB  - One of the preferred freshwater crayfish species in astaciculture is the large
      parastacid Cherax quadricarinatus, a native to Australia. This crayfish yields
      good production in warm water, and, therefore, it has been translocated from
      Australia to other countries. One such country is Uruguay, where the initial
      attempt in astaciculture is being conducted. In a Uruguayan crayfish farm, a
      large number of Diceratocephala boschmai (Platyhelminthes, Temnocephalida) were
      found on the body surface and branchial chamber of C. quadricarinatus. This is
      the first report of an introduced temnocephalidan in the New World, and of D.
      boschmai in a locality outside Australia/New Guinea. The original description of
      D. boschmai was based on a few characters that separated this species from the
      other Temnocephalida; therefore, a detailed description of the Uruguayan
      population of D. boschmai is also provided. The conditions in which D. boschmai
      is found in Uruguay are suitable for its development and reproduction. This
      raises concern about the effect that its release into the environment might have.

PMID- 18616380
TI  - Clutch morphology and the timing of exposure impact the susceptibility of aquatic
      insect eggs to esfenvalerate.
AB  - We investigated Baetis spp. (mayfly), Hesperoperla pacifica (stonefly), and
      Brachycentrus americanus (caddisfly) susceptibility at the egg stage to
      esfenvalerate, a synthetic pyrethroid insecticide. Eggs were obtained from the
      field or from field-collected gravid females at sites near Corvallis (OR, USA)
      and the Metolius River at Camp Sherman (OR, USA) for static exposures under
      controlled conditions for temperature and light. Eggs were exposed to
      esfenvalerate for 48 h at concentrations ranging from 0.025 to 4.0 microg/L. No
      effect on mortality or posthatch growth was detected in H. pacifica eggs exposed
      to esfenvalerate concentrations up to 1.0 microg/L. Exposure to 0.07 microg/L of
      esfenvalerate, however, caused a significant increase in Baetis spp. egg
      mortality, and exposure of near-eclosion eggs to lower concentrations (0.025 and
      0.05 microg/L) resulted in behavioral effects and reduced survivorship in newly
      hatched Baetis nymphs. Early stage B. americanus eggs were 10-fold more sensitive
      to esfenvalerate when removed from the gelatinous clutch before exposure, an
      indication that the gelatin affords protection from toxicant exposure. Exposures
      of near-hatch B. americanus clutches to esfenvalerate concentrations ranging
      between 0.035 and 0.2 microg/L, however, resulted in significant clutch death
      within clutches resulting from behavioral aberrations of first-instar larvae. The
      results of the present study suggest that aquatic insect egg clutch morphology
      can be a strong influence on susceptibility of embryos to esfenvalerate exposure.

PMID- 18616381
TI  - Impact of aquatic insect life stage and emergence strategy on sensitivity to
      esfenvalerate exposure.
AB  - We investigated the impact of aquatic insect life stage and emergence strategy on
      sensitivity to esfenvalerate, a synthetic pyrethroid insecticide, using field
      collected Brachycentrus americanus Banks (Trichoptera: Brachycentridae) and
      Cinygmula reticulata McDunnough (Ephemeroptera: Heptageniidae) insects. Final
      instar C. reticulata emergence was observed for one week following three
      environmentally relevant, 48-h esfenvalerate exposures (0.005, 0.01, and 0.015
      microg/L). Emergence was significantly depressed following exposure to
      esfenvalerate and resulted from an increase in nymph mortality during the
      emergence process. This experiment was duplicated for late-instar C. reticulata
      nymphs, which were similar in size to the final-instar nymphs but were not near
      emergence. Late-instar C. reticulata mayflies were approximately fivefold less
      sensitive to esfenvalerate exposures as gauged by one-week mortality rates.
      Brachycentrus americanus pupal mortality was significantly increased over that in
      controls following 48-h esfenvalerate exposures of 0.1 and 0.2 microg/L. These
      response concentrations correlated closely with those for case-abandonment rates
      of fourth-instar B. americanus larvae (a sublethal effect of esfenvalerate
      exposure). Pupal mortality rates were approximately 16-fold higher than those
      observed in larvae. Adult female egg weight as a percentage of total body weight
      was significantly decreased following pupal esfenvalerate exposures of 0.05, 0.1,
      and 0.2 microg/L. These findings suggest that exposure to esfenvalerate may
      impair hemimetabolous insect emergence behaviors and may decrease fecundity in
      holometabolous aquatic insects.

PMID- 18616382
TI  - Effects of dietary esfenvalerate exposures on three aquatic insect species
      representing different functional feeding groups.
AB  - Given the chemical properties of synthetic pyrethroids, it is probable that
      compounds, including esfenvalerate, that enter surface waters may become
      incorporated into aquatic insect food sources. We examined the effect of dietary
      esfenvalerate uptake in aquatic insects representing different functional feeding
      groups. We used three field-collected aquatic insect species: A grazing scraper,
      Cinygmula reticulata McDunnough (Ephemeroptera: Heptageniidae); an omnivorous
      filter feeder, Brachycentrus americanus Banks (Trichoptera: Brachycentridae); and
      a predator, Hesperoperla pacifica Banks (Plecoptera: Perlidae). Laboratory
      cultured algae were preexposed for 24 h to esfenvalerate concentrations of 0,
      0.025, 0.05, and 0.1 microg/L and provided to two C. reticulata age classes
      (small and final-instar nymphs). Reduction in small nymph growth was observed
      following three weeks of feeding on algae exposed to 0.05 and 0.1 microg/L of
      esfenvalerate, and the highest dietary exposure reduced egg production in final
      instar nymphs. The diet for B. americanus and H. pacifica consisted of dead third
      instar Chironomus tentans larvae preexposed for 24 h to esfenvalerate
      concentrations ranging between 0.1 and 1.0 microg/L. Consumption of larvae
      exposed to 0.5 to 1.0 microg/L of esfenvalerate caused case abandonment and
      mortality in B. americanus caddisfly larvae. Although H. pacifica nymphs readily
      consumed esfenvalerate-exposed larvae, no adverse effects were observed during
      the present study. Furthermore, no evidence of esfenvalerate-induced feeding
      deterrence was found in any of the species tested, suggesting that aquatic
      insects may not be able to distinguish between pyrethroid-contaminated and
      uncontaminated food sources. These findings indicate that feeding deterrence is
      not a factor in regulating aquatic insect dietary exposures to synthetic
      pyrethroids.

PMID- 18616383
TI  - Development of a new assay for evaluation of l-3,4-dihydroxyphenylalanine
      cytotoxicity in catalase-mutant Escherichia coli.
AB  - The present study aimed to assess whether a newly constructed, catalase-deficient
      Escherichia coli strain that express mammalian catalase gene could be used to
      identify oxidative stress-generating chemicals. We tested l-3,4
      dihydroxyphenylalanine (l-DOPA), a well-known agent that induces reactive oxygen
      species. We found that l-DOPA exposure reduced the survival of catalase-mutant E.
      coli in a dose-dependent manner, especially in the strains with lower catalase
      activities, implying the usefulness of these strains in assessment of oxidative
      chemicals.

PMID- 18616385
TI  - Derivation and characterization of two sibling human embryonic stem cell lines
      from discarded grade III embryos.
AB  - Human embryonic stem (hES) cells are a valuable tool for studying human
      development in addition to their potential applications in regenerative medicine
      and drug discovery. The role of genetic background and epigenetic influences in
      development as well as in response to external influences such as drugs and
      therapies is well recognized. The great ethnic diversity in the Indian
      subcontinent translates to interindividual variability in drug response and
      disease susceptibility. For these reasons, new hES cell lines representing Indian
      genetic diversity will be valuable in studies of tissue-differentiation, cellular
      function and for aspects of characterization of responses to drugs. We have
      derived two new hES cell lines, BJNhem19 and BJNhem20 from the inner cell mass
      (ICM) of discarded grade III human embryos that were not suitable for in vitro
      fertility treatment. Human leukocyte antigen (HLA) isotype analysis shows that
      they are genetically distinct from existing hES cell lines. Short tandem repeat
      (STR) analysis shows that the two cell lines are derived from sibling embryos.
      These cell lines show an undifferentiated phenotype in culture for more than 65
      passages, show normal karyotype and express pluripotency markers such as TRA-1
      60, TRA-1-81, stage-specific embryonic antigen-4 (SSEA-4), alkaline phosphatase,
      DNMT3B, GABRB3, GDF3, OCT4, NANOG, SOX2, TERF1, TDGF, LEFTA, THY1, and REX1.
      While both cell lines can differentiate into derivatives of all three germ layers
      in vitro, only BJNhem20 can form teratomas when transplanted into mice. We
      observe an increased frequency of cardiomyocyte differentiation from BJNhem20
      embryoid bodies in feeder-free cultures upon induction with DMSO. Cardiomyocytes
      purified from such cultures survive and show rhythmic contractions for several
      weeks in culture. These hES cell lines have been accepted for deposit in the U.K.
      Stem Cell Bank and will be a useful resource for the international stem cell
      community.

PMID- 18616387
TI  - Stage dynamics, period survival, and mortality plateaus.
AB  - Mortality plateaus at advanced ages have been found in many species, but their
      biological causes remain unclear. Here, we exploit age-from-stage methods for
      organisms with stage-structured demography to study cohort dynamics, obtaining
      age patterns of mortality by weighting one-period stage-specific survivals by
      expected age-specific stage structure. Cohort dynamics behave as a killed Markov
      process. Using as examples two African grasses, one pine tree, a temperate forest
      perennial herb, and a subtropical shrub in a hurricane-driven forest, we
      illustrate diverse patterns that may emerge. Age-specific mortality always
      reaches a plateau at advanced ages, but the plateau may be reached rapidly or
      slowly, and the trajectory may follow positive or negative senescence along the
      way. In variable environments, birth state influences mortality at early but not
      late ages, although its effect on the level of survivorship persists. A new
      parameter micro omega summarizes the risk of mortality averaged over the entire
      lifetime in a variable environment. Recent aging models for humans that employ
      nonobservable abstract states of "vitality" are also known to produce diverse
      trajectories and similar asymptotic behavior. We discuss connections, contrasts,
      and implications of our results to these models for the study of aging.

PMID- 18616388
TI  - Sexual size dimorphism predicts the frequency of sexual cannibalism within and
      among species of spiders.
AB  - Sexual cannibalism varies widely among spiders, but no general evolutionary
      hypothesis has emerged to explain its distribution across taxa. Sexual size
      dimorphism (SSD) also varies widely among spiders and could affect the
      vulnerability of males to cannibalistic attacks by females. We tested for a
      relationship between SSD and sexual cannibalism within and among species of
      spiders, using a broad taxonomic data set. For most species, cannibalism was more
      likely when males were much smaller than females. In addition, using
      phylogenetically controlled and uncontrolled analyses, there was a strong
      positive relationship between average SSD of a species and the frequency of
      sexual cannibalism. This is the first evidence that the degree of size difference
      between males and females is related to the phylogenetic distribution of sexual
      cannibalism among a broad range of spiders.

PMID- 18616390
TI  - Rapid antibacterial activity of 2 novel hand soaps: evaluation of the risk of
      development of bacterial resistance to the antibacterial agents.
AB  - OBJECTIVE: To evaluate the antimicrobial efficacy of and risk of organisms
      developing resistance to 2 novel hand soaps: (1) a soap containing triclosan,
      polyhexamethylene biguanide, and benzethonium chloride added to a soap base (TPB
      soap); and (2) a soap containing farnesol, polyhexamethylene biguanide, and
      benzethonium chloride added to a soap base (FPB soap). Tests also included soaps
      containing only triclosan. DESIGN: The risk of emergence of resistant bacterial
      mutants was investigated by determining the susceptibility changes after repeated
      exposure of bacteria to the drugs and soaps in vitro. The effectiveness of the
      soaps was evaluated using an in vitro tube dilution method, a volunteer method
      (the ASTM standard), and 2 pig skin methods. RESULTS: The minimum inhibitory
      concentration and minimum bactericidal concentration of triclosan against
      Staphylococcus aureus increased 8- to 62.5-fold, whereas those of TPB and FPB
      (both alone and in soap) were unchanged. In vitro, TPB and FPB soaps produced
      higher log(10) reductions in colony-forming units of all tested organisms (4.95
      8.58) than did soaps containing triclosan alone (0.29-4.86). In the test using
      the pig skin and volunteer methods, TPB soap produced a higher log(10) reduction
      in colony-forming units (3.1-3.3) than did the soap containing triclosan alone
      (2.6-2.8). CONCLUSION: The results indicate that TPB and FPB soaps may provide
      superior rapid and broad-spectrum efficacy with a lower risk of organisms
      developing resistance than do soaps containing triclosan alone. Pig skin methods
      may be used to predict the efficacy of antibacterial soaps in the rapid
      disinfection of contaminated hands. Hand washing with TPB and FPB soaps by
      healthcare workers and the general population may reduce the transmission of
      pathogens, with a lower risk of promoting the emergence of resistant organisms.

PMID- 18616389
TI  - A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and
      osteogenic differentiation of mesenchymal progenitor cells.
AB  - Pluripotent mesenchymal stem cells (MSCs) are bone marrow stromal progenitor
      cells that can differentiate into osteogenic, chondrogenic, adipogenic, and
      myogenic lineages. Several signaling pathways have been shown to regulate the
      lineage commitment and terminal differentiation of MSCs. Here, we conducted a
      comprehensive analysis of the 14 types of bone morphogenetic protein (BMPs) for
      their abilities to regulate multilineage specific differentiation of MSCs. We
      found that most BMPs exhibited distinct abilities to regulate the expression of
      Runx2, Sox9, MyoD, and PPARgamma2. Further analysis indicated that BMP-2, BMP-4,
      BMP-6, BMP-7, and BMP-9 effectively induced both adipogenic and osteogenic
      differentiation in vitro and in vivo. BMP-induced commitment to osteogenic or
      adipogenic lineage was shown to be mutually exclusive. Overexpression of Runx2
      enhanced BMP-induced osteogenic differentiation, whereas knockdown of Runx2
      expression diminished BMP-induced bone formation with a decrease in adipocyte
      accumulation in vivo. Interestingly, overexpression of PPARgamma2 not only
      promoted adipogenic differentiation, but also enhanced osteogenic differentiation
      upon BMP-2, BMP-6, and BMP-9 stimulation. Conversely, MSCs with PPARgamma2
      knockdown or mouse embryonic fibroblasts derived from PPARgamma2(-/-) mice
      exhibited a marked decrease in adipogenic differentiation, coupled with reduced
      osteogenic differentiation and diminished mineralization upon BMP-9 stimulation,
      suggesting that PPARgamma2 may play a role in BMP-induced osteogenic and
      adipogenic differentiation. Thus, it is important to understand the molecular
      mechanism behind BMP-regulated lineage divergence during MSC differentiation, as
      this knowledge could help us to understand the pathogenesis of skeletal diseases
      and may lead to the development of strategies for regenerative medicine.

PMID- 18616391
TI  - The renaissance of field experimentation in evaluating interventions.
AB  - Most experiments are done in laboratories. However, there is also a theory and
      practice of field experimentation. It has had its successes and failures over the
      past four decades but is now increasingly used for answering causal questions.
      This is true for both randomized and-perhaps more surprisingly-nonrandomized
      experiments. In this article, we review the history of the use of field
      experiments, discuss some of the reasons for their current renaissance, and focus
      the bulk of the article on the particular technical developments that have made
      this renaissance possible across four kinds of widely used experimental and quasi
      experimental designs-randomized experiments, regression discontinuity designs in
      which those units above a cutoff get one treatment and those below get another,
      short interrupted time series, and nonrandomized experiments using a
      nonequivalent comparison group. We focus this review on some of the key technical
      developments addressing problems that previously stymied accurate effect
      estimation, the solution of which opens the way for accurate estimation of
      effects under the often difficult conditions of field implementation-the
      estimation of treatment effects under partial treatment implementation, the
      prevention and analysis of attrition, analysis of nested designs, new analytic
      developments for both regression discontinuity designs and short interrupted time
      series, and propensity score analysis. We also cover the key empirical evidence
      showing the conditions under which some nonrandomized experiments may be able to
      approximate results from randomized experiments.

PMID- 18616392
TI  - Neuropsychological assessment of dementia.
AB  - Neuropsychological studies show that cognitive deficits associated with
      Alzheimer's disease (AD) are distinct from age-associated cognitive decline.
      Quantitative and qualitative differences are apparent across many cognitive
      domains, but are especially obvious in episodic memory (particularly delayed
      recall), semantic knowledge, and some aspects of executive functions. The
      qualitatively distinct pattern of deficits is less salient in very old AD
      patients than in younger AD patients. Although decline in episodic memory is
      usually the earliest cognitive change that occurs prior to the development of the
      AD dementia syndrome, asymmetry in cognitive abilities may also occur in this
      "preclinical" phase of the disease and predict imminent dementia. Discrete
      patterns of cognitive deficits occur in AD and several neuropathologically
      distinct age-associated neurodegenerative disorders. Knowledge of these
      differences helps to clinically distinguish among various causes of dementia and
      provides useful models for understanding brain-behavior relationships that
      mediate cognitive abilities affected in various neurodegenerative diseases.

PMID- 18616393
TI  - Novel method of murine embryonic stem cell-derived osteoclast development.
AB  - Murine embryonic stem (mES) cells are self-renewing pluripotent cells that bear
      the capacity to differentiate into ectoderm-, endoderm-, and mesoderm-derived
      tissues. In suspension culture, embryonic stem (ES) cells grow into spherical
      embryoid bodies (EBs) and are useful for the study of specific gene products in
      the development and function of various tissue types. Osteoclasts are
      hematopoietic stem cell-derived cells that participate in bone turnover by
      secreting resorptive molecules such as hydrochloric acid and acidic proteases,
      which degrade the bone extracellular matrix. Aberrant osteoclast function leads
      to dysplastic, erosive, and sclerosing bone diseases. Previous studies have
      reported the derivation of osteoclasts from mES cells; however, most of these
      protocols require coculture with stromal cell lines. We describe two simplified,
      novel methods of stromal cell-independent ES cell-derived osteoclast development.

PMID- 18616394
TI  - Osteopontin is increased in HIV-associated dementia.
AB  - Since the introduction of highly active antiretroviral therapy, survival rates
      for human immunodeficiency virus (HIV) infection have markedly improved, but less
      of an effect has been found for HIV-associated neurocognitive disorders. On the
      basis of our previous findings, we hypothesized that increased production of
      osteopontin might contribute to the persistence of central nervous system (CNS)
      dysfunctions. We found increased levels of osteopontin in the brains of humans
      with HIV encephalitis and monkeys with simian immunodeficiency virus (SIV)
      encephalitis. In cerebrospinal fluid, osteopontin levels were found to be
      elevated in HIV-infected individuals, regardless of their neuropsychological
      status. However, plasma osteopontin levels were significantly increased in
      individuals with HIV-associated dementia. In addition, a longitudinal study of
      monkeys revealed that plasma levels of osteopontin increased before the
      development of SIV-induced neurological and clinical abnormalities. Thus, plasma
      levels of osteopontin are significantly correlated with HIV-induced CNS
      dysfunction in the current era of efficacious antiviral treatment, and this
      finding suggests that the development of interventions to modulate osteopontin
      production or signaling might be beneficial in the prevention or treatment of HIV
      induced CNS disorders.

PMID- 18616395
TI  - Febrile Plasmodium falciparum malaria 4 years after exposure in a man with sickle
      cell disease.
AB  - We report a case of symptomatic Plasmodium falciparum malaria that manifested 4
      years after a visit to an area of endemicity in an 18-year-old male patient with
      sickle cell disease. The exceptionally long incubation time raises the questions
      of how and where P. falciparum parasites can reside for several years before
      suddenly causing disease.

PMID- 18616396
TI  - Extensively drug-resistant tuberculosis in california, 1993-2006.
AB  - BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a global public
      health emergency. We investigated the characteristics and extent of XDR TB in
      California to inform public health interventions. METHODS: XDR TB was defined as
      TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3
      injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre-XDR TB
      was defined as TB with resistance to isoniazid and rifampin and either a
      fluoroquinolone or second-line injectable agent but not both. We analyzed TB case
      reports submitted to the state TB registry for the period 1993-2006. Local health
      departments and the state TB laboratory were queried to ensure complete drug
      susceptibility reporting. RESULTS: Among 424 multidrug-resistant (MDR) TB cases
      with complete drug susceptibility reporting, 18 (4.2%) were extensively drug
      resistant, and 77 (18%) were pre-extensively drug resistant. The proportion of
      pre-XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 (P = .02)).
      Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were
      diagnosed in patients within 6 months after arrival in the United States. Mexico
      was the most common country of origin. Five cases (29%) of XDR TB were acquired
      during therapy in California. All patients with XDR TB had pulmonary disease, and
      most had prolonged infectious periods; the median time for conversion of sputum
      culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%)
      completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to
      receive treatment. CONCLUSIONS: XDR TB and pre-XDR TB cases comprise a
      substantial fraction of MDR TB cases in California, indicating the need for
      interventions that improve surveillance, directly observed therapy, and rapid
      drug susceptibility testing and reporting.

PMID- 18616397
TI  - The epidemiology, clinical features, and long-term prognosis of Japanese
      encephalitis in central sarawak, malaysia, 1997-2005.
AB  - BACKGROUND: Japanese encephalitis is a major public health problem in Asia.
      However, there is little data on the long-term outcome of Japanese encephalitis
      survivors. METHODS: We prospectively evaluated children with serologically
      confirmed Japanese encephalitis over an 8.3-year period. The patients were
      assessed and their outcomes were graded with a functional outcome score at
      hospital discharge and at follow-up appointments. We examined how patient outcome
      at hospital discharge compared with that at long-term follow-up visits, when
      changes in outcome occurred, and the prognostic indicators of the eventual
      outcome. RESULTS: One hundred and eighteen patients were recruited into the
      study, and 10 (8%) died during the acute phase of illness. At hospital discharge,
      44 (41%) of the 108 patients who survived had apparent full recovery; 3 (3%) had
      mild, 28 (26%) had moderate, and 33 (31%) had severe neurological sequelae.
      Eighty six of the 108 patients were followed up for a median duration of 52.9
      months (range, 0.9-114.9 months). During follow-up, 31 patients experienced
      improvement, but 15 patients experienced deterioration in their outcome grade. In
      most cases, assessment during the first 3-6 months after hospital discharge was
      predictive of the long-term outcome. More than one-half of the patients continued
      to experience neuropsychological sequelae and behavioral disorders. A combination
      of poor perfusion, Glasgow coma score < or =8, and > or =2 witnessed seizures
      predicted a poor long-term outcome with 65% sensitivity and 92% specificity.
      CONCLUSIONS: Neurological assessment of Japanese encephalitis survivors at
      hospital discharge does not predict long-term outcome. Seizures and shock are
      treatable risk factors for a poor outcome at hospital discharge and at long-term
      follow-up visits.

PMID- 18616398
TI  - Nicotiana benthamiana: its history and future as a model for plant-pathogen
      interactions.
AB  - Nicotiana benthamiana is the most widely used experimental host in plant
      virology, due mainly to the large number of diverse plant viruses that can
      successfully infect it. Additionally, N. benthamiana is susceptible to a wide
      variety of other plant-pathogenic agents (such as bacteria, oomycetes, fungi, and
      so on), making this species a cornerstone of host-pathogen research, particularly
      in the context of innate immunity and defense signaling. Moreover, because it can
      be genetically transformed and regenerated with good efficiency and is amenable
      to facile methods for virus-induced gene silencing or transient protein
      expression, N. benthamiana is rapidly gaining popularity in plant biology,
      particularly in studies requiring protein localization, interaction, or plant
      based systems for protein expression and purification. Paradoxically, despite
      being an indispensable research model, little is known about the origins, genetic
      variation, or ecology of the N. benthamiana accessions currently used by the
      research community. In addition to addressing these latter topics, the purpose of
      this review is to provide information regarding sources for tools and reagents
      that can be used to support research in N. benthamiana. Finally, we propose that
      N. benthamiana is well situated to become a premier plant cell biology model,
      particularly for the virology community, who as a group were the first to
      recognize the potential of this unique Australian native.

PMID- 18616399
TI  - Evaluation of constitutive viral promoters in transgenic soybean roots and
      nodules.
AB  - The efficiency of beta-glucuronidase (GUS) expression was evaluated with five
      viral promoters to identify the most suitable promoter or promoters for use in
      soybean hairy roots, including applications to study the symbiotic interaction
      with Bradyrhizobium japonicum. Levels of GUS activity were fluorimetrically and
      histochemically assayed when the GUS (uidA) gene was driven by the Cauliflower
      mosaic virus (CaMV) 35S promoter and enhanced 35S (E35S) promoter, the Cassava
      vein mosaic virus (CsVMV) promoter, the Figwort mosaic virus (FMV) promoter, and
      the Strawberry vein banding virus (SVBV2) promoter. We demonstrate that GUS
      activity was highest when driven by the FMV promoter and that the promoter
      activity of 35S and SVBV2 was significantly lower than that of the CsVMV and E35S
      promoters when tested in soybean hairy roots. In mature soybean root nodules,
      strong GUS activity was evident when the FMV, 35S, and CsVMV promoters were used.
      These results indicate that the FMV promoter facilitates the strong expression of
      target genes in soybean hairy roots and root nodules.

PMID- 18616401
TI  - A single amino acid of niapro of papaya ringspot virus determines host
      specificity for infection of papaya.
AB  - Most strains of Papaya ringspot virus (PRSV) belong to type W, causing severe
      loss on cucurbits worldwide, or type P, devastating papaya in tropical areas.
      While the host range of PRSV W is limited to plants of the families
      Chenopodiaceae and Cucuribitaceae, PRSV P, in addition, infects plants of the
      family Caricaceae (papaya family). To investigate one or more viral genetic
      determinants for papaya infection, recombinant viruses were constructed between
      PRSV P-YK and PRSV W-CI. Host reactions to recombinant viruses indicated that the
      viral genomic region covering the C-terminal region (142 residues) of NIaVPg,
      full NIaPro, and N-terminal region (18 residues) of NIb, is critical for papaya
      infection. Sequence analysis of this region revealed residue variations at
      position 176 of NIaVPg and positions 27 and 205 of NIaPro between type P and W
      viruses. Host reactions to the constructed mutants indicated that the amino acid
      Lys27 of NIaPro determines the host-specificity of PRSV for papaya infection.
      Predicted three-dimensional structures of NIaPros of parental viruses suggested
      that Lys27 does not affect the protease activity of NIaPro. Recovery of the
      infected plants from certain papaya-infecting mutants implied involvement of
      other viral factors for enhancing virulence and adaptation of PRSV on papaya.

PMID- 18616400
TI  - DsbB is required for the pathogenesis process of Xanthomonas campestris pv.
      campestris.
AB  - The DsbA/DsbB oxidation pathway is one of the two pathways that catalyze
      disulfide bond formation of proteins in the periplasm of gram-negative bacteria.
      It has been demonstrated that DsbA is essential for multiple virulence factors of
      several animal bacterial pathogens. In this article, we present genetic evidence
      to show that the open reading frame XC_3314 encodes a DsbB protein that is
      involved in disulfide bond formation in periplasm of Xanthomonas campestris pv.
      campestris, the causative agent of crucifer black rot disease. The dsbB mutant of
      X. campestris pv. campestris exhibited attenuation in virulence, hypersensitive
      response, cell motility, and bacterial growth in planta. Furthermore, mutation in
      the dsbB gene resulted in ineffective type II and type III secretion systems as
      well as flagellar assembly. These findings reveal that DsbB is required for the
      pathogenesis process of X. campestris pv. campestris.

PMID- 18616402
TI  - Role of ammonia secretion and pH modulation on pathogenicity of Colletotrichum
      coccodes on tomato fruit.
AB  - Colletotrichum coccodes was found to alkalinize the decaying tissue of tomato
      fruit via accumulation and secretion of ammonia. Alkalinization dynamics caused
      by ammonia secretion from growing hyphae was examined microscopically using the
      pH-sensitive fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein.
      Values of pH of 7.9 observed in the host tissue close to the hyphal tips declined
      to pH 6.0 at 10 mm away from the hyphal tip, which was a value that was still
      higher than that detected in the healthy tissue, pH 4.2. Ammonia accumulation at
      the infection site depended on the initial environmental pH. Treatments with low
      (4.0) pH buffer at the infection site resulted in high levels of ammonia
      secretion and increased virulence of C. coccodes compared with similar treatments
      with buffer at pH 7.0. Significantly, mutants of C. coccodes defective in
      nitrogen utilization, nit-, and areA- were impaired in ammonia secretion and
      showed reduced decay development. The reduced infection rate of nit- mutants
      could be complemented by adding glutamine at the infection site. Thus, ammonia
      accumulation is a critical factor contributing to C. coccodes pathogenicity on
      tomato fruit. The results show that the initial acidic pH of the fruit is
      conducive to ammonia secretion and the subsequent alkalinization of the infection
      site, and facilitates fungal virulence and the transformation from the quiescent
      biotrophic to active-necrotrophic state.

PMID- 18616403
TI  - 2R,3R-butanediol, a bacterial volatile produced by Pseudomonas chlororaphis O6,
      is involved in induction of systemic tolerance to drought in Arabidopsis
      thaliana.
AB  - Root colonization of plants with certain rhizobacteria, such as Pseudomonas
      chlororaphis O6, induces tolerance to biotic and abiotic stresses. Tolerance to
      drought was correlated with reduced water loss in P. chlororaphis O6-colonized
      plants and with stomatal closure, indicated by size of stomatal aperture and
      percentage of closed stomata. Stomatal closure and drought resistance were
      mediated by production of 2R,3R-butanediol, a volatile metabolite of P.
      chlororaphis O6. Root colonization with bacteria deficient in 2R,3R-butanediol
      production showed no induction of drought tolerance. Studies with Arabidopsis
      mutant lines indicated that induced drought tolerance required the salicylic acid
      (SA)-, ethylene-, and jasmonic acid-signaling pathways. Both induced drought
      tolerance and stomatal closure were dependent on Aba-1 and OST-1 kinase.
      Increases in free SA after drought stress of P. chlororaphis O6-colonized plants
      and after 2R,3R-butanediol treatment suggested a primary role for SA signaling in
      induced drought tolerance. We conclude that the bacterial volatile 2R,3R
      butanediol was a major determinant in inducing resistance to drought in
      Arabidopsis through an SA-dependent mechanism.

PMID- 18616404
TI  - Erwinia amylovora type three-secreted proteins trigger cell death and defense
      responses in Arabidopsis thaliana.
AB  - Erwinia amylovora is the bacterium responsible for fire blight, a necrotic
      disease affecting plants of the rosaceous family. E. amylovora pathogenicity
      requires a functional type three secretion system (T3SS). We show here that E.
      amylovora triggers a T3SS-dependent cell death on Arabidopsis thaliana. The
      plants respond by inducing T3SS-dependent defense responses, including salicylic
      acid (SA)-independent callose deposition, activation of the SA defense pathway,
      reactive oxygen species (ROS) accumulation, and part of the jasmonic
      acid/ethylene defense pathway. Several of these reactions are similar to what is
      observed in host plants. We show that the cell death triggered by E. amylovora on
      A. thaliana could not be simply explained by the recognition of AvrRpt2 ea by the
      resistance gene product RPS2. We then analyzed the role of type three-secreted
      proteins (T3SPs) DspA/E, HrpN, and HrpW in the induction of cell death and
      defense reactions in A. thaliana following infection with the corresponding E.
      amylovora mutant strains. HrpN and DspA/E were found to play an important role in
      the induction of cell death, activation of defense pathways, and ROS
      accumulation. None of the T3SPs tested played a major role in the induction of SA
      independent callose deposition. The relative importance of T3SPs in A. thaliana
      is correlated with their relative importance in the disease process on host
      plants, indicating that A. thaliana can be used as a model to study their role.

PMID- 18616405
TI  - Expression of the Bradyrhizobium japonicum type III secretion system in legume
      nodules and analysis of the associated tts box promoter.
AB  - In Bradyrhizobium japonicum, as in some other rhizobia, symbiotic efficiency is
      influenced by a type III secretion system (T3SS). Most genes encoding the
      transport machinery and secreted proteins are preceded by a conserved 30-bp
      motif, the type-three secretion (tts) box. In this study, we found that regions
      downstream of 34 tts boxes are transcribed. For nopB, nopL, and gunA2, the
      transcriptional start sites were found to be 12, 11, and 10 bp downstream of
      their tts boxes, respectively. The deletion of this motif or modification of two
      or more conserved residues strongly reduced expression of nopB. This indicates
      that the tts box is an essential promoter element. Data obtained with lacZ
      reporter gene fusions of five genes preceded by a tts box (gunA2, nopB, rhcV,
      nopL, and blr1806) revealed that they are expressed in 4-week-old nodules of
      Macroptilium atropurpureum. These data suggest that the T3SS is active in mature
      nitrogen-fixing nodules. The two-component response regulator TtsI is required
      for the expression of rhcV, nopL, and blr1806 in bacteroids. Staining of
      inoculated roots showed that nopB is also expressed in early infection stages.

PMID- 18616406
TI  - Quorum-sensing system affects gall development incited by Pantoea agglomerans pv.
      gypsophilae.
AB  - The quorum-sensing (QS) regulatory system of the gall-forming Pantoea agglomerans
      pv. gypsophilae was identified. Mass spectral analysis, together with signal
      specific biosensors, demonstrated that P. agglomerans pv. gypsophilae produced N
      butanoyl-l-homoserine lactone (C4-HSL) as a major and N-hexanoyl-l-homoserine
      lactone (C6-HSL) as a minor QS signal. Homologs of luxI and luxR regulatory
      genes, pagI and pagR, were characterized in strain P. agglomerans pv. gypsophilae
      Pag824-1 and shown to be convergently transcribed and separated by 14 bp. The
      deduced PagI (23.8 kDa) and PagR (26.9 kDa) show high similarity with SmaI (41%
      identity) and SmaR (43% identity), respectively, of Serratia sp. American Type
      Culture Collection 39006. PagR possesses characteristic autoinducer binding and a
      helix-turn-helix DNA-binding domain. Gall formation by P. agglomerans pv.
      gypsophilae depends on a plasmid-borne hrp/hrc gene cluster, type III effectors,
      and phytohormones. Disruption of pagI, pagR, or both genes simultaneously in
      Pag824-1 reduced gall size in gypsophila cuttings by 50 to 55% when plants were
      inoculated with 10(6) CFU/ml. Higher reductions in gall size (70 to 90%) were
      achieved by overexpression of pagI or addition of exogenous C4-HSL. Expression of
      the hrp/hrc regulatory gene hrpL and the type III effector pthG in the pagI
      mutant, as measured with quantitative reverse-transcriptase polymerase chain
      reaction, was reduced by 5.8 and 6.6, respectively, compared with the wild type,
      suggesting an effect of the QS system on the Hrp regulon.

PMID- 18616407
TI  - Phloem unloading of potato virus X movement proteins is regulated by virus and
      host factors.
AB  - To determine the requirements for viral proteins exiting the phloem, transgenic
      plants expressing green fluorescent protein (GFP) fused to the Potato virus X
      (PVX) triple gene block (TGB)p1 and coat protein (CP) genes were prepared. The
      fused genes were transgenically expressed from the companion cell (CC)-specific
      Commelina yellow mottle virus (CoYMV) promoter. Transgenic plants were selected
      for evidence of GFP fluorescence in CC and sieve elements (SE) and proteins were
      determined to be phloem mobile based on their ability to translocate across a
      graft union into nontransgenic scions. Petioles and leaves were analyzed to
      determine the requirements for phloem unloading of the fluorescence proteins. In
      petioles, fluorescence spread throughout the photosynthetic vascular cells
      (chlorenchyma) but did not move into the cortex, indicating a specific barrier to
      proteins exiting the vasculature. In leaves, fluorescence was mainly restricted
      to the veins. However, in virus-infected plants or leaves treated with a cocktail
      of proteasome inhibitors, fluorescence spread into leaf mesophyll cells. These
      data indicate that PVX contributes factors which enable specific unloading of
      cognate viral proteins and that proteolysis may play a role in limiting proteins
      in the phloem and surrounding chlorenchyma.

PMID- 18616408
TI  - Evidence for the involvement in nodulation of the two small putative regulatory
      peptide-encoding genes MtRALFL1 and MtDVL1.
AB  - Nod factors are key bacterial signaling molecules regulating the symbiotic
      interaction between bacteria known as rhizobia and leguminous plants. Studying
      plant host genes whose expression is affected by Nod factors has given insights
      into early symbiotic signaling and development. Here, we used a double
      supernodulating mutant line that shows increased sensitivity to Nod factors to
      study the Nod factor-regulated transcriptome. Using microarrays containing more
      than 16,000 70-mer oligonucleotide probes, we identified 643 Nod-factor-regulated
      genes, including 225 new Nod-factor-upregulated genes encoding many potential
      regulators. Among the genes found to be Nod factor upregulated, we identified and
      characterized MtRALFL1 and MtDVL1, which code for two small putative peptide
      regulators of 135 and 53 amino acids, respectively. Expression analysis confirmed
      that these genes are upregulated during initial phases of nodulation.
      Overexpression of MtRALFL1 and MtDVL1 in Medicago truncatula roots resulted in a
      marked reduction in the number of nodules formed and in a strong increase in the
      number of aborted infection threads. In addition, abnormal nodule development was
      observed when MtRALFL1 was overexpressed. This work provides evidence for the
      involvement of new putative small-peptide regulators during nodulation.

PMID- 18616409
TI  - Genome-scale mutagenesis and phenotypic characterization of two-component signal
      transduction systems in Xanthomonas campestris pv. campestris ATCC 33913.
AB  - The gram-negative bacterium Xanthomonas campestris pv. campestris is the causal
      agent of black rot disease of cruciferous plants. Its genome encodes a large
      repertoire of two-component signal transduction systems (TCSTSs), which consist
      of histidine kinases and response regulators (RR) to monitor and respond to
      environmental stimuli. To investigate the biological functions of these TCSTS
      genes, we aimed to inactivate all 54 RR genes in X. campestris pv. campestris
      ATCC 33913, and successfully generated 51 viable mutants using the insertion
      inactivation method. Plant inoculation identified two novel response regulator
      genes (XCC1958 and XCC3107) that are involved in virulence of this strain.
      Genetic complementation demonstrated that XCC3107, designated as vgrR (virulence
      and growth regulator), also affects bacterial growth and activity of
      extracellular proteases. In addition, we assessed the survival of these mutants
      under various stresses, including osmotic stress, high sodium concentration, heat
      shock, and sodium dodecyl sulfate exposure, and identified a number of genes that
      may be involved in the general stress response of X. campestris pv. campestris.
      Mutagenesis and phenotypic characterization of RR genes in this study will
      facilitate future studies on signaling networks in this important phytopathogenic
      bacterium.

PMID- 18616411
TI  - Novel biologic mechanisms of levosimendan and its effect on the failing heart.
AB  - BACKGROUND: Calcium sensitizers belong to a new class of cardiac enhancers that
      stimulate cardiac contractility without causing intracellular calcium overload or
      increasing myocardial oxygen demand. Levosimendan, the most well-studied calcium
      sensitizer in the real clinical practice, produces greater hemodynamic and
      symptomatic improvement in patients with acute heart failure than traditional
      inotropes. OBJECTIVE: To review the recent experimental and clinical evidence on
      novel biologic mechanisms explaining the pleiotropic effects of levosimendan on
      the failing heart. METHODS: A systematic search of peer-reviewed publications was
      performed on Medline and EMBASE from January 1995 to December 2007. The results
      of unpublished trials were obtained from presentations at national and
      international meetings. RESULTS: Levosimendan has a unique dual mechanism of
      action by enhancing cardiac contractility and causing peripheral vasodilatation.
      Immunomodulatory and antiapoptotic properties of levosimendan may be an
      additional biologic mechanism that prevents further cytotoxic and hemodynamic
      consequences of abnormal immune and neurohormonal responses in acute heart
      failure, leads to cardioprotection, and beneficially intervenes in the
      progression of syndrome. Experimental data show that levosimendan exerts its
      cardioprotective effects through its antioxidant properties and seems to be a
      potent inhibitor of H2O2-induced cardiomyocyte apoptotic cell death. Clinical
      data demonstrate that levosimendan does not increase markers of oxidative and
      nitrosative stress, in contrast to placebo treatment, in advanced chronic heart
      failure patients. Levosimendan has also been shown to activate mitoK(ATP)
      channels which are important mediators of ischemic preconditioning.
      Pharmacological modulation of K(ATP) channels may prove beneficial in patients at
      risk of myocardial ischemia, particularly those requiring inotropic support.
      CONCLUSION: Pleiotropic effects of levosimendan appear to have important clinical
      and prognostic implications in acute heart failure syndromes and ischemic heart
      disease.

PMID- 18616412
TI  - Plant histaminase as an investigational drug in splanchnic artery occlusion and
      reperfusion.
AB  - BACKGROUND: Amine oxidases are ubiquitous enzymes involved in the metabolism of
      biogenic amines. Copper amine oxidases catalyze the oxidative deamination of
      primary amine groups of several biogenic amines, such as putrescine, cadaverine
      and histamine. OBJECTIVE: In the present review the effects of a plant amine
      oxidase (histaminase, EC1.4.3.6), purified from pea seedlings, in the prevention
      of splanchnic postischemic reperfusion damage are reported. CONCLUSION: Various
      studies have clearly indicated that the use of histaminase will offer a good
      perspective for a novel therapeutic approach in the medical treatment of
      intestinal ischemia.

PMID- 18616413
TI  - Induced hypothermia in acute ischemic stroke.
AB  - BACKGROUND: Induced hypothermia is a promising neuroprotective treatment for
      acute ischemic stroke. Data from both global and focal ischemia animal models
      have been encouraging. However, only a few small clinical studies have
      investigated its use in humans. OBJECTIVE: To review the background, possible
      mechanisms of action, and the preclinical and clinical data supporting the
      neuroprotective role of induced hypothermia following acute ischemic stroke.
      METHODS: A literature search was performed using the PubMed database. Only papers
      in English were reviewed. RESULTS/CONCLUSIONS: Induced hypothermia is effective
      as a neuroprotectant in animal models of acute ischemic stroke. Its multimodal
      mechanism of action makes it a very attractive method of neuroprotection.
      Although human studies suggest it is safe and feasible, larger randomized
      controlled trials are necessary to address clinical efficacy and to refine the
      methods and parameters of induced hypothermia protocols.

PMID- 18616414
TI  - Carbamylated erythropoietin to treat neuronal injury: new development strategies.
AB  - BACKGROUND: Carbamylated erythropoietin (CEPO) is a modified erythropoietin
      molecule not affecting hematocrit. It is a potentially important pharmacological
      agent that may be applied to the treatment of several diseases affecting central
      and peripheral system neurons. OBJECTIVE: Carbamylated erythropoietin is a prime
      candidate for development because of its potent cell survival and function
      enhancing effects. This article reviews the preclinical development profile of
      CEPO in animal models to determine whether further clinical development is
      justified. METHODS: The review spans a detailed analysis of patents and
      scientific publications related to CEPO in animal models. RESULTS/CONCLUSIONS:
      Use of CEPO in treating diseases such as stroke and traumatic brain and spinal
      cord injuries is important because these conditions affect millions of patients
      every year. Extensive preclinical studies support further clinical studies of
      CEPO for acute ischemic stroke. However, further studies are required for testing
      CEPO in patients with many other indications.

PMID- 18616415
TI  - New drugs in development for the treatment of endometriosis.
AB  - Endometriosis is a common and enigmatic disease causing pelvic pain and
      infertility. Current treatment is mainly based on the use of surgery and ovarian
      suppressive agents. There is in particular the need for new therapeutic options
      able to allow a normal menstrual cycle to occur and also consent pregnancy. In
      the present review, we aimed to give a concise and practical overview in order to
      allow the clinician to clearly understand the level of development of these
      drugs. We have presented only treatments supported by in vivo researches with a
      special attention to studies in humans. Results show appealing new possibilities
      are emerging from agents counteracting the endometriosis-associated inflammation.
      Recent data also suggests that there is still the opportunity to refine the use
      of already available agents.

PMID- 18616416
TI  - Anti-TNF-alpha therapies in chronic obstructive pulmonary diseases.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma are chronic
      diseases in which inflammation of the airways leads to progressive transient
      airway obstruction and TNF-alpha plays an important pro-inflammatory role.
      OBJECTIVE: To assess the plausibility of anti-TNF-alpha therapies playing an anti
      inflammatory role in asthma and COPD. METHODS: Scientific rationale of TNF-alpha
      targeting in asthma and COPD was assessed individually and the available data on
      the use of anti-TNF-alpha in each disease were reviewed. RESULTS AND CONCLUSION:
      Anti-TNF-alpha therapies demonstrate different efficacies in asthma and COPD and
      further supportive preclinical and clinical data are needed, especially about
      subsets of certain diseases which could benefit the most from these therapies.

PMID- 18616417
TI  - Inflammatory lipids as a target for therapy in the rheumatic diseases.
AB  - As patients with autoimmune rheumatic diseases live longer due to improved
      therapies and preventive measures, death and disability from cardiovascular
      events are increasing. Patients with rheumatoid arthritis and systemic lupus
      erythematosus have an increased risk of atherosclerosis that persists even after
      accounting for traditional cardiac risk factors. Recent studies strongly suggest
      that the mechanism is due in part to increased levels of oxidized lipids (such as
      oxidized low density lipoprotein and pro-inflammatory high density lipoproteins)
      which cause the inflammatory cascade that ultimately leads to plaque formation.
      The objective of this review is to discuss how inflammatory lipids contribute to
      the increased risk of atherosclerosis in rheumatoid arthritis and systemic lupus
      erythematosus, as well as to propose that these oxidized lipids are a rational
      target for therapeutic intervention in autoimmune diseases. Published literature
      was examined to review treatments for pro-inflammatory lipids in autoimmune
      diseases such as rheumatoid arthritis and systemic lupus erythematosus. In
      conclusion, it is possible that these oxidized lipids may also contribute to
      increased disease manifestations in rheumatic conditions. Several new and
      existing therapies, including statins and high density lipoprotein-associated
      protein peptide mimetics such as D-4F (apoA-1) target these oxidized lipids and
      may be useful in both preventing atherosclerosis and treating inflammation in
      patients with rheumatic diseases.

PMID- 18616418
TI  - Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with
      promising activity for glioblastoma multiforme.
AB  - BACKGROUND: Glioblastoma multiforme (GBM), a highly invasive and vascular cancer,
      responds poorly to conventional cytotoxic therapy. Integrins, widely expressed in
      GBM and tumor vasculature, mediate cell survival, migration and angiogenesis.
      Cilengitide is a potent alphavbeta3 and alphavbeta5 integrin inhibitor.
      OBJECTIVE: To summarize the preclinical and clinical experience with cilengitide
      for GBM. METHODS: Preclinical studies and clinical trials evaluating cilengitide
      for GBM were reviewed. RESULTS/CONCLUSIONS: Cilengitide is active and synergizes
      with external beam radiotherapy in preclinical GBM models. In clinical trials for
      recurrent GBM, single-agent cilengitide has antitumor benefits and minimal
      toxicity. Among newly diagnosed GBM patients, single-arm studies incorporating
      cilengitide into standard external beam radiotherapy/temozolomide have shown
      encouraging activity with no increased toxicity and have led to a planned
      randomized Phase III trial.

PMID- 18616419
TI  - ZD4054: a specific endothelin A receptor antagonist with promising activity in
      metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: Overexpression of the endothelin A (ET(A)) receptor has been found in
      a number of human cancer cell lines. Activation of the ET(A) receptor by
      endothelin-1 (ET-1) promotes cell proliferation and survival in these tumors,
      whereas activation of the endothelin B (ET(B)) receptor results in an opposing
      effect. Therefore, blockade of ET(A) may have antitumor effects, while sparing
      ET(B)-mediated effects such as induction of apoptosis and clearance of ET-1.
      OBJECTIVE: ZD4054 is an orally bioavailable, specific ET(A) antagonist currently
      being investigated in prostate cancer. In receptor-binding studies, ZD4054 only
      bound to ET(A), with no binding detected towards ET(B). Prostate cancer cell
      lines are known to produce ET-1 and there is a relative increase in expression of
      ET(A) to ET(B) in these cancers. There is also an association of greater ET(A)
      expression in higher grade versus lower grade tumors, suggesting that ET(A) may
      be involved in the malignant transformation process. As ET-1 may also mediate
      nociceptive effects and osteoblastic effects, there is much interest in
      clinically assessing ZD4054 in prostate cancer. METHODS: The data describing the
      endothelin axis, the role of ET(A) and ET(B) in malignancy, and the effects of
      ET(A) antagonist ZD4054 in prostate cancer, as demonstrated in preclinical and
      clinical studies, are reviewed. RESULTS: Further investigation of ZD4054 in
      prostate cancer is warranted, and Phase III trials are already planned in
      patients with non-metastatic castrate-resistant prostate cancer (CRPC) with
      rising prostate specific antigen values, metastatic (asymptomatic) CRPC, and in
      metastatic CRPC in combination with docetaxel, assessing either differences in
      progression-free survival and overall survival or overall survival alone.

PMID- 18616420
TI  - Promising antitumor activity with MGCD0103, a novel isotype-selective histone
      deacetylase inhibitor.
AB  - BACKGROUND: Histone deacetylases (HDACs), which target histones as well as non
      histone proteins as substrates, have the potential to regulate aberrant gene
      expression and restore normal growth control in malignancies. OBJECTIVE: This
      review provides an updated summary of preclinical and clinical experience with
      the oral isotype-selective HDAC inhibitor MGCD0103 in cancer. METHODS: Data
      presented in abstract form from international conferences or journal articles
      found within a PubMed search of article up to May 2008 are described in this
      review. RESULTS/CONCLUSIONS: MGCD0103 appears tolerable and exhibits favorable
      pharmacokinetic and pharmacodynamic profiles with evidence of target inhibition
      in surrogate tissues. Clinical and pharmacodynamic data support a three-times
      weekly administration at a 90-mg fixed dose. MGCD0103 displays promising
      antitumor activity in hematological and lymphoproliferative diseases.

PMID- 18616421
TI  - Darusentan: a new perspective for treatment of resistant hypertension?
AB  - Despite multi-drug therapy, hypertension remains uncontrolled in a significant
      amount of patients, especially those with multiple cardiovascular risk factors.
      Endothelin-1 is a long lasting and very potent vasoconstrictor and plays a key
      role in cardiovascular hemostasis. Endothelin mediates its biological activity in
      humans through the endothelin A and B receptors. The selective endothelin--A
      receptor antagonist darusentan may be a new treatment option in patients with
      resistant hypertension. The objectives were that the clinical experience and the
      evidence for therapy with darusentan in resistant systemic hypertension were
      reviewed. The methods by the authors were that the leading journals which publish
      basic science and clinical research in the area of cardiovascular diseases and
      PubMed were scanned. In conclusion, early clinical results from Phase II studies
      suggest that darusentan may find a place in the treatment of resistant
      hypertension.

PMID- 18616423
TI  - Communication between the synapse and the nucleus in neuronal development,
      plasticity, and disease.
AB  - Sensory experience is critical for the proper development and plasticity of the
      brain throughout life. Successful adaptation to the environment is necessary for
      the survival of an organism, and this process requires the translation of
      specific sensory stimuli into changes in the structure and function of relevant
      neural circuits. Sensory-evoked activity drives synaptic input onto neurons
      within these behavioral circuits, initiating membrane depolarization and calcium
      influx into the cytoplasm. Calcium signaling triggers the molecular mechanisms
      underlying neuronal adaptation, including the activity-dependent transcriptional
      programs that drive the synthesis of the effector molecules required for long
      term changes in neuronal function. Insight into the signaling pathways between
      the synapse and the nucleus that translate specific stimuli into altered patterns
      of connectivity within a circuit provides clues as to how activity-dependent
      programs of gene expression are coordinated and how disruptions in this process
      may contribute to disorders of cognitive function.

PMID- 18616424
TI  - Replicative aging in yeast: the means to the end.
AB  - Progress in aging research is now rapid, and surprisingly, studies in a single
      celled eukaryote are a driving force. The genetic modulators of replicative life
      span in yeast are being identified, the molecular events that accompany aging are
      being discovered, and the extent to which longevity pathways are conserved
      between yeast and multicellular eukaryotes is being tested. In this review, we
      provide a brief retrospective view on the development of yeast as a model for
      aging and then turn to recent discoveries that have pushed aging research into
      novel directions and also linked aging in yeast to well-developed hypotheses in
      mammals. Although the question of what causes aging still cannot be answered
      definitively, that day may be rapidly approaching.

PMID- 18616425
TI  - Systems approaches to identifying gene regulatory networks in plants.
AB  - Complex gene regulatory networks are composed of genes, noncoding RNAs, proteins,
      metabolites, and signaling components. The availability of genome-wide
      mutagenesis libraries; large-scale transcriptome, proteome, and metabalome data
      sets; and new high-throughput methods that uncover protein interactions
      underscores the need for mathematical modeling techniques that better enable
      scientists to synthesize these large amounts of information and to understand the
      properties of these biological systems. Systems biology approaches can allow
      researchers to move beyond a reductionist approach and to both integrate and
      comprehend the interactions of multiple components within these systems.
      Descriptive and mathematical models for gene regulatory networks can reveal
      emergent properties of these plant systems. This review highlights methods that
      researchers are using to obtain large-scale data sets, and examples of gene
      regulatory networks modeled with these data. Emergent properties revealed by the
      use of these network models and perspectives on the future of systems biology are
      discussed.

PMID- 18616426
TI  - The epigenetics of rRNA genes: from molecular to chromosome biology.
AB  - In eukaryotes, the genes encoding ribosomal RNAs (rDNA) exist in two distinct
      epigenetic states that can be distinguished by a specific chromatin structure
      that is maintained throughout the cell cycle and is inherited from one cell to
      another. The fact that even in proliferating cells with a high demand of protein
      synthesis a fraction of rDNA is silenced provides a unique possibility to
      decipher the mechanism underlying epigenetic regulation of rDNA. This chapter
      summarizes our knowledge of the molecular mechanisms that establish and propagate
      the epigenetic state of rRNA genes, unraveling a complex interplay of DNA
      methyltransferases and histone-modifying enzymes that act in concert with
      chromatin remodeling complexes and RNA-guided mechanisms to define the
      transcriptional state of rDNA. We also review the critical role of the RNA
      polymerase I transcription factor UBF in the formation of active nucleolar
      organizer regions (NORs) and maintenance of the euchromatic state of rRNA genes.

PMID- 18616427
TI  - Sister chromatid cohesion: a simple concept with a complex reality.
AB  - In eukaryotes, the process of sister chromatid cohesion holds the two sister
      chromatids (the replicated chromosomes) together from DNA replication to the
      onset of chromosome segregation. Cohesion is mediated by cohesin, a four-subunit
      SMC (structural maintenance of chromosome) complex. Cohesin and cohesion are
      required for proper chromosome segregation, DNA repair, and gene expression. To
      carry out these functions, cohesion is regulated by elaborate mechanisms
      involving a growing list of cohesin auxiliary factors. These factors control the
      timing and position of cohesin binding to chromatin, activate chromatin-bound
      cohesin to become cohesive, and orchestrate the orderly dissolution of cohesion.
      The 45-nm ringlike architecture of soluble cohesin is compatible with
      dramatically different mechanisms for both chromatin binding and cohesion
      generation. Solving the mechanism of cohesion and its complex regulation presents
      significant challenges but offers the potential to provide important insights
      into higher-order chromosome organization and chromosome biology.

PMID- 18616428
TI  - The evolution, regulation, and function of placenta-specific genes.
AB  - A number of placenta-specific genes (e.g., Tpbp, Plac1, Syncytin, and
      retrotransposon-associated genes such as Peg10, Rtl1, Endothelin B receptor,
      Insl4, Leptin, Midline1, and Pleiotrophin), enhancer elements (e.g., glycoprotein
      hormone alpha-subunit) and gene isoforms (e.g., 3betaHSD, Cyp19), as well as
      placenta-specific members of gene families (e.g., Gcm1, Mash2, Rhox, Esx1,
      Cathepsin, PAG, TKDP, Psg, Siglec) have been identified. This review summarizes
      their evolution, regulation, and biochemical functions and discusses their
      significance for placental development and function. Strikingly, the number of
      unique, truly placenta-specific genes that have been discovered to date is very
      small. The vast majority of placenta-specific gene products have resulted from
      one of three mechanisms: evolution of placenta-specific promoters, evolution of
      large gene families with several placenta-specific members, or adoption of
      functions associated with endogenous retroviruses and retroelements.
      Interestingly, nearly all the examples of placenta-specific genes that have been
      discovered to date are not present in all placental mammals.

PMID- 18616429
TI  - Role of the domain encompassing Arg304-Ile328 in rat P2X2 receptor conformation
      revealed by alterations in complex glycosylation at Asn298.
AB  - The final 25 amino acids of the ectodomain of the P2X receptors, immediately
      prior to the second TM (transmembrane domain) (pre-TM2: Arg(304)-Ile(328) in rat
      P2X(2)), are highly conserved. Whole-cell patch clamp recordings showed that
      single cysteine substitutions in the N-terminal half of pre-TM2 (Arg(304)
      Ile(314)) led to loss of function at Arg(304), Leu(306), Lys(308) and Ile(312).
      Cysteine substitutions within this region also resulted in a significant
      reduction in the apparent molecular mass of receptors, due to loss of complex
      glycosylation at the nearby acceptor site Asn(298), which was not seen for the C
      terminal portion of pre-TM2 (Asp(315)-Ile(328)). The reduction in complex
      glycosylation was not due to reduced cell-surface presentation, demonstrating
      that glycosylation at Asn(298) was acting as a sensor of subtle changes in
      receptor conformation within the pre-TM2 region. When this N-glycan site was
      repositioned closer to the plasma membrane by mutagenesis (N298S together with
      G299N, T300N, T301N or T303N), glycosylation was restored at G299N and T300N, but
      was impaired for T301N and completely absent for T303N. These results suggest
      that the region in the vicinity of Asp(315) is at the plasma membrane interface
      and that the N-terminal portion of pre-TM2 (Arg(304)-Ile(314)) is important for
      the correct conformation of the receptor at the extracellular face of the
      membrane.

PMID- 18616430
TI  - Compartmentalized DCC signalling is distinct from DCC localized to lipid rafts.
AB  - BACKGROUND INFORMATION: Netrin-1 is a bi-functional cue that attracts or repels
      different classes of neurons during development. The netrin-1 receptor DCC
      (deleted in colorectal cancer) acts as a tyrosine kinase-associated receptor to
      mediate the attractive response towards netrin-1. The lipid raft-localized Src
      family kinase Fyn is required for DCC-mediated axon guidance. DCC functions are
      also dependent on lipid rafts, membrane microdomains corresponding to a low
      density, detergent-resistant membrane fraction. However, it remains unclear how
      the association of DCC with lipid rafts controls netrin-1 signalling. RESULTS:
      DCC targeted to lipid rafts represented a minor proportion of total DCC inside
      the cell, but predominated on the cell surface of both IMR-32 human neuroblastoma
      cells and embryonic cortical neurons. Netrin-1 accumulated in lipid rafts, but
      had no effect on the targeting of DCC to that compartment, with DCC remaining on
      the cell surface in lipid rafts through 60 min post-treatment. However, DCC was
      able to interact with Fyn, both in the lipid rafts and soluble compartments
      isolated from embryonic E19 rat brains, whereas early downstream signalling
      components such as Nck-1, and total and active focal adhesion kinase were mainly
      localized to the non-lipid raft compartment. CONCLUSIONS: Together, these results
      suggest that DCC can be found in raft and non-raft portions of the plasma
      membrane, with early signalling events propagated by non-raft associated DCC.

PMID- 18616432
TI  - Interpreting urine drug tests: prevalence of morphine metabolism to hydromorphone
      in chronic pain patients treated with morphine.
AB  - OBJECTIVE: Pain medicine practitioners frequently use urine drug testing (UDT) to
      monitor adherence to opioid therapy. It can be difficult to interpret a result as
      normal or abnormal in relation to which opioid compounds are expected to be found
      in the urine. We investigated whether hydromorphone may be a metabolite of
      morphine normally appearing in UDT of patients prescribed morphine. DESIGN: This
      is a retrospective case-control study of urine toxicology results in pain
      patients taking only morphine. Inclusion criteria included urine results positive
      for morphine only (controls) or morphine and hydromorphone (cases). Demographic
      and medical history variables, and any history of aberrant drug behavior were
      recorded and related to the presence or absence of hydromorphone in the urine.
      RESULTS: Hydromorphone was present in 21 of 32 cases (66%), none of whom had a
      history of aberrant drug behavior. Positive cases occurred more frequently in
      women, in those taking higher daily doses of morphine, and in those with higher
      urine morphine concentrations (P < 0.05). Only morphine urine concentration was a
      significant predictor of the hydromorphone metabolite in a logistic regression
      model (P < 0.05). CONCLUSIONS: Hydromorphone is likely a minor metabolite of
      morphine, normally appearing in the UDT of patients taking morphine. This finding
      assists in determining whether a UDT result is normal or abnormal, and
      subsequently whether a patient is compliant with opioid therapy. This observation
      should be confirmed by a prospective study in a controlled environment. Variables
      such as gender, morphine dose, morphine urine concentration, and genetic
      determinants of morphine metabolism should be investigated further.

PMID- 18616433
TI  - Systematic review of emergency physician-performed ultrasonography for lower
      extremity deep vein thrombosis.
AB  - OBJECTIVES: The authors performed a systematic review to evaluate published
      literature on diagnostic performance of emergency physician-performed
      ultrasonography (EPPU) for the diagnosis and exclusion of deep venous thrombosis
      (DVT). METHODS: Structured search criteria were used to query MEDLINE and EMBASE,
      followed by a hand search of published bibliographies. Relevance and inclusion
      criteria required prospective investigation of emergency department (ED)
      outpatients with suspected DVT; diagnostic evaluations had to consist of EPPU
      followed by criterion standard (radiology-performed) imaging. Two authors
      independently extracted data from included studies; study quality was assessed
      utilizing a validated tool for quality assessment of diagnostic accuracy studies
      (QUADAS). Pooled data were analyzed using an unweighted summary receiver
      operating-characteristic (SROC) curve; sensitivity and specificity were estimated
      using a random effects model. RESULTS: The initial search yielded 1,162
      publications. Relevance screening and selection yielded six articles including
      936 patients. Four of the six studies reported adequate blinding but a number of
      other methodologic flaws were identified. A random effects model yielded an
      overall sensitivity of 0.95 (95% confidence interval [CI] = 0.87 to 0.99) and
      specificity of 0.96 (95% CI = 0.87 to 0.99). CONCLUSIONS: Systematic review of
      six studies suggests that EPPU may be accurate for the diagnosis of DVT compared
      with radiology-performed ultrasound (US). However, given the methodologic
      limitations identified among the primary studies, the estimates of diagnostic
      test performance may be overly optimistic. Further research into EPPU for
      suspected DVT is needed before it can be adopted into routine clinical practice.

PMID- 18616434
TI  - Use of a standardized order set for achieving target temperature in the
      implementation of therapeutic hypothermia after cardiac arrest: a feasibility
      study.
AB  - OBJECTIVES: Induced hypothermia (HT) after cardiac arrest improved outcomes in
      randomized trials. Current post-cardiac arrest treatment guidelines advocate HT;
      however, utilization in practice remains low. One reported barrier to adoption is
      clinician concern over potential technical difficulty of HT. We hypothesized that
      using a standardized order set, clinicians could achieve HT target temperature in
      routine practice with equal or better efficiency than that observed in randomized
      trials. METHODS: After a multidisciplinary HT education program, we implemented a
      standardized order set for HT induction and maintenance including sedation and
      paralysis, intravenous cold saline infusion, and an external cooling apparatus,
      with a target temperature range of 33-34 degrees C. We performed a retrospective
      analysis of a prospectively compiled and maintained registry of cardiac arrest
      patients with HT attempted (intent-to-treat) over the first year of
      implementation. The primary outcome measures were defined a priori by
      extrapolating treatment arm data from the largest and most efficacious randomized
      trial: 1) successful achievement of target temperature for >or=85% of patients in
      the cohort and 2) median time from return of spontaneous circulation (ROSC) to
      achieving target temperature <8 hours. RESULTS: Clinicians attempted HT on 23
      post-cardiac arrest patients (arrest location: 78% out-of-hospital, 22% in
      hospital; initial rhythm: 26% ventricular fibrillation/tachycardia, 70% pulseless
      electrical activity or asystole) and achieved the target temperature in 22/23
      (96%) cases. Median time from ROSC to target temperature was 4.4 (interquartile
      range 2.8-7.2) hours. Complication rates were low. CONCLUSIONS: Using a
      standardized order set, clinicians can achieve HT target temperature in routine
      practice.

PMID- 18616435
TI  - Can the emergency department algorithm detect changes in access to care?
AB  - OBJECTIVES: The "emergency department algorithm" (EDA) uses emergency department
      (ED) diagnoses to assign probabilities that a visit falls into each of four
      categories: nonemergency, primary care-treatable emergency, preventable emergency
      needing ED care, and nonpreventable emergency. The EDA's developers report that
      it can evaluate the medical safety net because patients with worse access to care
      will use EDs for less urgent conditions. After the Oregon Health Plan (OHP,
      Oregon's expanded Medicaid program) underwent cutbacks affecting access to care
      in 2003, the authors tested the ability of the EDA to detect changes in ED use.
      METHODS: All visits to 22 Oregon EDs during 2002 were compared with visits during
      2004. For each payer category, mean probabilities that ED visits fell into each
      of the four categories were compared before versus after the OHP cutbacks.
      RESULTS: The largest change in mean probabilities after the cutbacks was 2%.
      Attempts to enhance the sensitivity of the EDA through other analytic strategies
      were unsuccessful. By contrast, ED visits by the uninsured increased from
      6,682/month in 2002 to 9,058/month in 2004, and the proportion of uninsured
      visits leading to hospital admission increased by 51%. CONCLUSIONS: The EDA was
      less useful in demonstrating changes in access to care than were other, simpler
      measures. Methodologic concerns with the EDA that may account for this limitation
      are discussed. Given the widespread adoption of the EDA among health policy
      researchers, the authors conclude that further refinement of the methodology is
      needed.

PMID- 18616436
TI  - Independent evaluation of an out-of-hospital termination of resuscitation (TOR)
      clinical decision rule.
AB  - OBJECTIVES: Recently, investigators described a clinical decision rule for
      termination of resuscitation (TOR) designed to help determine whether to
      terminate emergency medical services (EMS) resuscitative efforts for out-of
      hospital cardiac arrests (OOHCA). The authors sought to evaluate the hypothesis
      that TOR would predict no survival for patients in an independent cohort of
      patients with OOHCA. METHODS: This was a retrospective cohort analysis conducted
      in the state of Arizona. Consecutive, adult, OOHCA were prospectively evaluated
      from October 2004 through October 2006. A statewide OOHCA database utilizing
      Utstein-style reporting from 30 different EMS systems was used. Data were
      abstracted from EMS first care reports and hospital discharge records. The TOR
      guidelines predict that no survival to hospital discharge will occur if 1) an
      OOHCA victim does not have return of spontaneous circulation (ROSC), 2) no shocks
      are administered, and 3) the arrest is not witnessed by EMS personnel. Data were
      entered into a structured database. Continuous data are presented as means (+/
      standard deviations [SD]) and categorical data as frequency of occurrence, and
      95% confidence intervals (CIs) were calculated as appropriate. The primary
      outcome measure was to determine if any cohort member who met TOR criteria
      survived to hospital discharge. RESULTS: There were 2,239 eligible patients; the
      study group included 2,180 (97.4%) patients for whom the data were complete; mean
      age was 64 (+/-11) years, and 35% were female. The majority of patients in the
      study group met at least one or more of the TOR criteria. A total of 2,047
      (93.8%) patients suffered from cardiac arrest that was unwitnessed by EMS; 1,653
      (75.8%) had an unwitnessed arrest and no ROSC. With respect to TOR, 1,160 of
      2,180 (53.2%) patients met all three criteria; only one (0.09%; 95% CI = 0% to
      0.5%) survived to hospital discharge. CONCLUSIONS: The authors evaluated TOR
      guidelines in an independent, statewide OOHCA database. The results are
      consistent with the findings of the TOR investigation and suggest that this
      algorithm is a promising tool for TOR decision-making in the field.

PMID- 18616431
TI  - Role of peroxisome-proliferator-activated receptor beta/delta (PPARbeta/delta) in
      gastrointestinal tract function and disease.
AB  - PPARbeta/delta (peroxisome-proliferator-activated receptor beta/delta) is one of
      three PPARs in the nuclear hormone receptor superfamily that are collectively
      involved in the control of lipid homoeostasis among other functions.
      PPARbeta/delta not only acts as a ligand-activated transcription factor, but also
      affects signal transduction by interacting with other transcription factors such
      as NF-kappaB (nuclear factor kappaB). Constitutive expression of PPARbeta/delta
      in the gastrointestinal tract is very high compared with other tissues and its
      potential physiological roles in this tissue include homoeostatic regulation of
      intestinal cell proliferation/differentiation and modulation of inflammation
      associated with inflammatory bowel disease and colon cancer. Analysis of mouse
      epithelial cells in the intestine and colon has clearly demonstrated that ligand
      activation of PPARbeta/delta induces terminal differentiation. The PPARbeta/delta
      target genes mediating this effect are currently unknown. Emerging evidence
      suggests that PPARbeta/delta can suppress inflammatory bowel disease through
      PPARbeta/delta-dependent and ligand-independent down-regulation of inflammatory
      signalling. However, the role of PPARbeta/delta in colon carcinogenesis remains
      controversial, as conflicting evidence suggests that ligand activation of
      PPARbeta/delta can either potentiate or attenuate this disease. In the present
      review, we summarize the role of PPARbeta/delta in gastrointestinal physiology
      and disease with an emphasis on findings in experimental models using both high
      affinity ligands and null-mouse models.

PMID- 18616437
TI  - Children with bacterial meningitis presenting to the emergency department during
      the pneumococcal conjugate vaccine era.
AB  - BACKGROUND: The epidemiology of bacterial meningitis in children in the era of
      widespread heptavalent conjugate pneumococcal vaccination (PCV7) is unknown.
      OBJECTIVES: The objective was to describe the epidemiology of bacterial
      meningitis in children presenting to the emergency department (ED) during the era
      of widespread PCV7 vaccination. METHODS: The authors retrospectively reviewed the
      medical records of all children aged 1 month to 19 years with bacterial
      meningitis who presented to the EDs of 20 U.S. pediatric centers (2001-2004).
      Bacterial meningitis was defined by a positive cerebrospinal fluid (CSF) culture
      for a bacterial pathogen or CSF pleocytosis (CSF white blood cell [WBC] count
      >or=10 cells/mm(3)) in association with either a positive blood culture or a CSF
      latex agglutination study. RESULTS: A total of 231 children with bacterial
      meningitis were identified. The median age was 0.6 years (interquartile range
      [IQR] = 0.2-4.2). Eight patients (3% of all patients) died. The following
      bacterial pathogens were identified: Streptococcus pneumoniae (n = 77; 33.3%),
      Neisseria meningitidis (67; 29.0%), Group B Streptococcus (42; 18.2%),
      Escherichia coli (17; 7.4%), nontypeable Haemophilus influenzae (10; 4.3%), other
      Gram-negative bacilli (7; 3.0%), Listeria monocytogenes (5; 2.2%), Group A
      Streptococcus (5; 2.2%), and Moraxella catarrhalis (1; 0.4%). S. pneumoniae
      serotypes were determined in 37 of 77 patients; of these, 62% were due to
      nonvaccine serotypes (including 19A). CONCLUSIONS: Although now a rare infectious
      disease in United States, bacterial meningitis still causes substantial morbidity
      in affected children. Despite the introduction of PCV7, S. pneumoniae remains the
      most common cause of bacterial meningitis in U.S. children, with approximately
      half of cases due to nonvaccine serotypes.

PMID- 18616438
TI  - Untreated hypertension and the emergency department: a chance to intervene?
AB  - OBJECTIVES: Untreated hypertension (HTN) is a major public health problem.
      Screening for untreated HTN in the emergency department (ED) may lead to
      appropriate treatment of more patients. The authors investigated the accuracy of
      identifying HTN in the ED, the proportion of ED patients with untreated HTN,
      patient characteristics predicting untreated HTN, and provider documentation of
      untreated HTN. METHODS: The authors performed a retrospective cross-sectional
      study on a random sample of 2,061 adults treated at an urban academic ED. The
      validity of six candidate definitions of HTN in the ED was assessed in a
      subsample using outpatient clinic records as the reference standard. "Untreated
      HTN" was HTN without a HTN medication listed in the ED history. "Documentation of
      untreated HTN was documentation of HTN as a visit problem, specific referral for
      HTN, or ED discharge with a HTN" information sheet or a HTN medication.
      Multivariable logistic regression was used to determine associations. RESULTS:
      The preferred definition of HTN in the ED had sensitivity of 86% (95% confidence
      interval [CI] = 80% to 90%), specificity of 78% (95% CI = 69% to 85%), and
      accuracy of 83% (95% CI = 78% to 87%). Of the 42% (95% CI = 40% to 44%) of ED
      patients with HTN, 43% (95% CI = 39% to 46%) had untreated HTN. Patients who were
      younger and male, without primary care physicians, with fewer prior ED visits,
      and without cardiovascular comorbidities, had higher odds of untreated HTN. Of
      those with untreated HTN, 8% (95% CI = 5% to 11%) had their untreated HTN
      documented. CONCLUSIONS: Untreated HTN was common in the ED but rarely
      documented. Providers can use ED blood pressures along with patient
      characteristics to identify those with untreated HTN for referral to primary
      care.

PMID- 18616439
TI  - Predictive value of T-wave abnormalities at the time of emergency department
      presentation in patients with potential acute coronary syndromes.
AB  - OBJECTIVES: T-wave abnormalities on electrocardiograms (ECGs) are common, but
      their ability to predict 30-day cardiovascular outcomes at the time of emergency
      department (ED) presentation is unknown. The authors determined the association
      between T-wave abnormalities on the presenting ECG and cardiovascular outcomes
      within 30 days of presentation in patients with potential acute coronary
      syndromes (ACSs). METHODS: This was a secondary analysis of a prospective cohort
      study of ED patients that presented with a potential ACS. Patients were excluded
      if they had a prior myocardial infarction, ST-segment elevation or depressions,
      right or left bundle branch block, or Q-waves on the initial ECG. Data included
      demographics, medical and cardiac history, and ECG findings including the
      presence or absence of T-wave flattening, inversions of 1-5 mm, and inversions >5
      mm. Investigators followed the hospital course for admitted patients, and 30-day
      follow-up was performed on all patients. The main outcome was a composite of
      death, acute myocardial infarction, revascularization, coronary stenosis greater
      than 50%, or a stress test with reversible ischemia. RESULTS: Of 8,298 patient
      visits, 5,582 met criteria for inclusion: 4,166 (74.6%) had no T-wave
      abnormalities, 721 (12.9%) had T-wave flattening in two or more leads, 659
      (11.8%) had T-wave inversions of 1-5 mm, and 36 (0.64%) had T-wave inversions >5
      mm. The composite endpoint was more common in patients with T-wave flattening
      (8.2% vs. 5.7%; p = 0.0001; relative risk [RR] = 1.4; 95% confidence interval
      [CI] = 1.1 to 1.9), T-wave inversions 1-5 mm (13.2% vs. 5.7%; p = 0.0001; RR =
      2.4; 95% CI = 1.8 to 3.1), and T-wave inversions >5 mm (19.4% vs. 5.7%; p =
      0.0001; RR = 3.4; 95% CI = 1.7 to 6.1), or any T-wave abnormality (10.8% vs.
      5.7%; p = 0.0001; RR = 1.9; 95% CI = 1.6 to 2.3), even after adjustment for
      initial troponin. This association also existed in the subset of patients without
      known coronary artery disease. CONCLUSIONS: In patients with potential ACS
      presenting to the ED, T-wave abnormalities are associated with higher rates of 30
      day cardiovascular events.

PMID- 18616441
TI  - Impact of disaster drills on patient flow in a pediatric emergency department.
AB  - OBJECTIVES: Joint Commission on Accreditation of Healthcare Organizations (JCAHO)
      accredited hospitals must conduct disaster drills twice a year, with one
      incorporating a mass casualty incident to the emergency department (ED). The
      authors found no studies describing the potential negative impact on the quality
      of care real patients in the ED receive during these drills. The objective was to
      determine the impact that mass casualty drills have on the timeliness of care for
      nondisaster patients in a pediatric ED. METHODS: Since 2001, nine disaster drills
      involving mass casualties to the ED were conducted at the authors' institution.
      The authors studied 5-, 10-, and 24-hour blocks of time surrounding these events
      and defined quality measures as the timeliness of care in terms of length of stay
      (LOS) in ED, time-to-triage, and time-to-physician. Drill dates were compared
      with control dates (the same weekday on the following week). Paired t-tests were
      used to compare outcomes of interest between drill and control days. RESULTS:
      Nine drill days and nine control days were studied. There was no statistically
      significant difference between drill dates and control dates in average time-to
      triage and time-to-emergency physician and average ED LOS. Admitted patients
      spent less time in the ED during drill dates. CONCLUSIONS: Disaster drills at
      this institution do not appear to significantly affect the timeliness of care to
      nondisaster drill ED patients. Attention should be paid to the quality of care
      "real" patients receive to ensure that their care is not jeopardized during an
      artificial stress to the system during a disaster drill.

PMID- 18616442
TI  - Apoptosis and necrosis in the ischemic zone adjacent to third degree burns.
AB  - OBJECTIVES: Burns are characterized by a central zone of necrosis surrounded by a
      zone of potentially reversible ischemia. The authors explored the contribution of
      necrosis and apoptosis to cell death in the zone of ischemia. METHODS: A
      previously established rat contact thermal injury model that utilizes a brass
      comb to produce four distinctive burns sites separated by three "interspaces" of
      unburned skin was used. The interspaces represent the zone of stasis or ischemia
      while the burn sites represent the zone of coagulation. With this model, most
      unburned interspaces progress to necrosis over 2 to 3 days. Full-thickness 3-mm
      biopsies were obtained from the interspaces, burns, and normal skin controls at
      30 minutes, 24 hours, and 48 hours after injury. Slides were stained with
      hematoxylin and eosin as well as activated cleaved caspase-3 (CC3a) for evidence
      of apoptosis and high-mobility group box 1 (HMGB1) for evidence of necrosis.
      RESULTS: Necrosis was not seen at 30 minutes, but was found in a large number of
      cells within the epidermis, sebaceous glands, and follicles at 24 and 48 hours.
      Faint nuclear CC3a staining indicative of apoptosis was present in a minority of
      cells within the epidermis, dermal fibroblasts, dermal follicles, and dermal
      sebaceous glands at 30 minutes and to a lesser degree at 24 and 48 hours.
      CONCLUSIONS: Both early apoptosis and delayed necrosis are present in the zone of
      ischemia, contributing to injury progression. Necrosis appears to play a larger
      role than apoptosis in injury progression in the comb burn model.

PMID- 18616443
TI  - Technology-driven or patient outcome-driven use of emergency department
      ultrasound for deep vein thrombosis assessment.

PMID- 18616444
TI  - Hypothermia after cardiac arrest: we can do this.

PMID- 18616445
TI  - Productivity and career paths of previous recipients of Society for Academic
      Emergency Medicine research grant awards.
AB  - OBJECTIVES: The objective was to assess productivity of previous recipients of
      Society for Academic Emergency Medicine (SAEM) grant awards. METHODS: All
      previous recipients of SAEM Research Training Grants, Neuroscience Research
      Awards, Scholarly Sabbatical Awards, and Emergency Medical Services (EMS)
      Research Fellowship awards funded through 2004 were identified through SAEM's
      records and surveyed. Award categories assessed were those still offered by SAEM
      at the time of the survey and therefore excluded the Geriatric Research Award.
      The 2005-2006 SAEM Grants Committee developed a survey using previous
      publications assessing productivity of training grants and fellowship awards and
      refined it through consensus review and limited pilot testing. We assessed
      measures of academic productivity (numbers of publications and additional grants
      awarded), commitment to an academic career, satisfaction with the SAEM award, and
      basic demographic information. RESULTS: Overall response rate was 70%; usable
      data were returned by all seven Research Training Grant awardees, both
      Neuroscience awardees, four of five Scholarly Sabbatical awardees, and six of 14
      EMS Research Fellowship awardees. Of those who gave demographic information, 78%
      (14/18) were male and 94% (16/17) were non-Hispanic white. All the respondents
      remained in academics, and 14 of 19 felt that they will definitely be in
      academics 5 years from the time of the survey. They have a median of 1.8 original
      research publications per year since the end of their grant period, and 74%
      (14/19) have received subsequent federal funding. All found the SAEM award to be
      helpful or very helpful to their careers. CONCLUSIONS: Previous recipients of the
      SAEM grant awards show evidence of academic productivity in the form of
      subsequent grant funding and research publications, and the majority remain
      committed to and satisfied with their academic research careers.

PMID- 18616446
TI  - Scholarship in emergency medicine in an environment of increasing clinical
      demand: proceedings from the 2007 Association of American Medical Colleges annual
      meeting.
AB  - Academic emergency medicine can benefit by broadening the way in which
      scholarship is defined to include teaching, integration of knowledge, application
      of knowledge to practical clinical problems and as discovery of new knowledge. A
      broad view of scholarship will help foster innovation and may lead to new areas
      of expertise. The creation of a scholarly environment in emergency medicine faces
      the continued challenge of an increasing clinical demand. The solution to this
      dilemma will likely require a mix of clinical staff physicians and academic
      faculty who are appreciated, nurtured and rewarded in different ways, for the
      unique contributions they make to the overall success of the academic program.

PMID- 18616447
TI  - Informed consent for research: current practices in academic emergency medicine.
AB  - BACKGROUND: The emergency department (ED) environment presents unique barriers to
      the process of obtaining informed consent for research. OBJECTIVES: The objective
      was to identify commonalities and differences in informed consent practices for
      research employed in academic EDs. METHODS: Between July 1, 2006, and June 30,
      2007, an online survey was sent to the research directors of 142 academic
      emergency medicine (EM) residency training programs identified through the
      Accreditation Council for Graduate Medical Education (ACGME). RESULTS: Seventy
      one (50%) responded. The average number of simultaneous clinical ED-based
      research projects reported was 7.3 (95% confidence interval [CI] = 5.53 to 9.07).
      Almost half (49.3%) of respondents reported that EM residents are responsible for
      obtaining consent. Twenty-nine (41.4%) participating institutions do not require
      documentation of an individual resident's knowledge of the specific research
      protocol and consent procedure before he or she is allowed to obtain consent from
      research subjects. CONCLUSIONS: It is common practice in academic EDs for
      clinical investigators to rely on on-duty health care personnel to obtain
      research informed consent from potential research subjects. This practice raises
      questions regarding the sufficiency of the information received by research
      subjects, and further study is needed to determine the compliance of this consent
      process with federal guidelines.

PMID- 18616448
TI  - Multicenter study of limited health literacy in emergency department patients.
AB  - OBJECTIVES: The objective was to evaluate the prevalence of limited health
      literacy and its association with sociodemographic variables in emergency
      department (ED) patients. METHODS: This was a cross-sectional survey in three
      Boston EDs. The authors enrolled consecutive adult patients during two 24-hour
      periods at each site. They measured health literacy by the short version of the
      Test of Functional Health Literacy in Adults (S-TOFHLA). Using multivariate
      logistic regression, the authors evaluated associations between sociodemographic
      variables and limited health literacy, as classified by S-TOFHLA scores. RESULTS:
      The authors enrolled 300 patients (77% of eligible). Overall, 75 (25%; 95%
      confidence interval [CI] = 20% to 30%) of participants had limited health
      literacy. Limited health literacy was independently associated with older age
      (compared to 18-44 years, odds ratio [OR] 4.3 [95% CI = 2.0 to 9.2] for 45-64
      years and OR 3.4 [95% CI = 1.4 to 8.5] for >or=65 years), less education
      (compared to high school graduates, OR 2.7 [95% CI = 1.1 to 7.3] for some high
      school or lower and OR 0.43 [95% CI = 0.21 to 0.88] for some college or higher),
      and lower income (OR 2.8 [95% CI = 1.2 to 6.6] for <or=$40,000 compared to
      >$40,000). Although ethnicity, race, and language were associated with limited
      health literacy in unadjusted analyses, the associations were not significant on
      multivariate analysis. CONCLUSIONS: In this sample, one-quarter of ED patients
      would be expected to have difficulty understanding health materials and following
      prescribed treatment regimens. Advanced age and low socioeconomic status were
      independently associated with limited health literacy. The ability of a
      significant subgroup of ED patients to understand health information, especially
      during illness or injury, requires further study.

PMID- 18616449
TI  - Who can speak for the emergently ill? Testing a method to identify communities
      and their leaders.
AB  - OBJECTIVES: The Food and Drug Administration (FDA) requires researchers to
      consult with the community prior to conducting research with exception from
      informed consent, but little is known about whether people support this and, if
      they do, who researchers should consult. We sought to determine if people could
      identify communities and leaders of those communities who researchers should
      consult with to represent their views about research that requires an exception
      from informed consent. METHODS: We conducted a cross-sectional interview study
      using a convenience sample of patients seeking care in an urban emergency
      department (ED) to determine if people belonged to specific communities and, if
      they did, if they could identify communities and leaders appropriate for
      consultation. Descriptive statistics were used to represent our findings.
      RESULTS: Most of the 262 participants approached for the study completed the
      interview (199; 76%). Of those interviewed, 122 (61%) were African American, 54
      (27%) were white, 83 (42%) were male, and the mean (+/-standard deviation [SD])
      age was 36.2 +/- 14.4 years. Most, (194; 97%), identified that they belonged to a
      community and most (177; 89%), said that researchers could consult at least one
      of their communities for consultation about an exception from informed consent
      study. Participants typically named geographic and religious-affiliated
      communities and leaders as appropriate for consultation. CONCLUSION: Most
      participants identified a community and a leader of that community who
      researchers could consult about research with exception from informed consent.
      Geographic and faith-based organizations could play an important role in
      consultation.

PMID- 18616450
TI  - Diagnosis of ascending aortic dissection using emergency department bedside
      echocardiogram.

PMID- 18616451
TI  - Management of posterior epistaxis.

PMID- 18616460
TI  - Two CYP17 genes in the South African Angora goat (Capra hircus) - the
      identification of three genotypes that differ in copy number and steroidogenic
      output.
AB  - In mammals, cytochrome P450 17alpha-hydroxylase/17-20 lyase (CYP17), which is
      encoded by a single gene, plays a critical role in the production of
      mineralocorticoids, glucocorticoids and androgens by the adrenal cortex. Two
      CYP17 isoforms with unique catalytic properties have been identified in the South
      African Angora goat (Capra hircus), a subspecies that is susceptible to cold
      stress because of the inability of the adrenal cortex to produce sufficient
      levels of cortisol. A real-time-based genotyping assay was used in this study to
      identify the distribution of the two CYP17 alleles in the South African Angora
      population. These data revealed that the two CYP17 isoforms were not the product
      of two alleles of the same gene, but two separate CYP17 genes encoding the two
      unique CYP17 isoforms. This novel finding was subsequently confirmed by
      quantitative real-time PCR. Goats were divided into three unique genotypes which
      differed not only in the genes encoding CYP17, but also in copy number.
      Furthermore, in vivo assays revealed that the identified genotypes differed in
      their ability to produce cortisol in response to intravenous insulin injection.
      This study clearly demonstrates the presence of two CYP17 genes in the South
      African Angora goat, and further implicates CYP17 as the primary cause of the
      observed hypocortisolism in this subspecies.

PMID- 18616461
TI  - Regulation of ERK1/2 phosphorylation by acute and chronic morphine - implications
      for the role of cAMP-responsive element binding factor (CREB)-dependent and Ets
      like protein-1 (Elk-1)-dependent transcription; small interfering RNA-based
      strategy.
AB  - Extracellular signal-regulated kinases (ERKs) have been shown to be activated by
      opioids and functionally linked to addiction. Morphine-associated changes in ERK
      activity seem to be the characteristic features of opioid action. In this study,
      we observed a rapid and severe increase in ERK1/2 activity after a 5 min morphine
      treatment of HEK-MOR cells (transfected with the rat mu-opioid receptor MOR1)
      expressing mu-opioid receptor. Cellular adaptations to chronic (72 h) morphine
      treatment were manifested by a slight and sustained increase in ERK1/2 activity.
      Withdrawal caused by an opioid receptor antagonist - naloxone - attenuated
      phosphorylation of ERK1/2. Little information is available on the precise
      mechanism of ERK activity regulation. Using RNA interference technology, we
      generated stably transfected cells with silenced expression of cAMP-responsive
      element binding factor (CREB) and Ets-like protein-1 (Elk-1) transcription
      factors, which are known targets for activated ERK1/2. In these cells, ERK1/2
      activity regulation was altered. Silencing of CREB or Elk-1 significantly
      increased ERK activation observed after 5 min of morphine stimulation. The
      initial level of activated ERKs in these cells was also augmented. Moreover, the
      cellular response to withdrawal signals and chronic opioid treatment was
      diminished. These differences suggest that both CREB-dependent and Elk-1
      dependent transcription contribute to the expression of proteins regulating
      morphine-induced ERK activity (particular phosphatases, upstream kinases or their
      activatory proteins).

PMID- 18616462
TI  - The product chain length determination mechanism of type II geranylgeranyl
      diphosphate synthase requires subunit interaction.
AB  - The product chain length determination mechanism of type II geranylgeranyl
      diphosphate synthase from the bacterium, Pantoea ananatis, was studied. In most
      types of short-chain (all-E) prenyl diphosphate synthases, bulky amino acids at
      the fourth and/or fifth positions upstream from the first aspartate-rich motif
      play a primary role in the product determination mechanism. However, type II
      geranylgeranyl diphosphate synthase lacks such bulky amino acids at these
      positions. The second position upstream from the G(Q/E) motif has recently been
      shown to participate in the mechanism of chain length determination in type III
      geranylgeranyl diphosphate synthase. Amino acid substitutions adjacent to the
      residues upstream from the first aspartate-rich motif and from the G(Q/E) motif
      did not affect the chain length of the final product. Two amino acid insertion in
      the first aspartate-rich motif, which is typically found in bacterial enzymes, is
      thought to be involved in the product determination mechanism. However, deletion
      mutation of the insertion had no effect on product chain length. Thus, based on
      the structures of homologous enzymes, a new line of mutants was constructed in
      which bulky amino acids in the alpha-helix located at the expected subunit
      interface were replaced with alanine. Two mutants gave products with longer chain
      lengths, suggesting that type II geranylgeranyl diphosphate synthase utilizes an
      unexpected mechanism of chain length determination, which requires subunit
      interaction in the homooligomeric enzyme. This possibility is strongly supported
      by the recently determined crystal structure of plant type II geranylgeranyl
      diphosphate synthase.

PMID- 18616463
TI  - Salt-resistant homodimeric bactenecin, a cathelicidin-derived antimicrobial
      peptide.
AB  - The cathelicidin antimicrobial peptide bactenecin is a beta-hairpin molecule with
      a single disulfide bond and broad antimicrobial activity. The proform of
      bactenecin exists as a dimer, however, and it has been proposed that bactenecin
      is released as a dimer in vivo, although there has been little study of the
      dimeric form of bactenecin. To investigate the effect of bactenecin dimerization
      on its biological activity, we characterized the dimer's effect on phospholipid
      membranes, the kinetics of its bactericidal activity, and its salt sensitivity.
      We initially synthesized two bactenecin dimers (antiparallel and parallel) and
      two monomers (beta-hairpin and linear). Under oxidative folding conditions,
      reduced linear bactenecin preferentially folded into a dimer forming a ladder
      like structure via intermolecular disulfide bonding. As compared to the monomer,
      the dimer had a greater ability to induce lysis of lipid bilayers and was more
      rapidly bactericidal. Interestingly, the dimer retained antimicrobial activity at
      physiological salt concentrations (150 mm NaCl), although the monomer was
      inactivated. This salt resistance was also seen with bactenecin dimer containing
      one intermolecular disulfide bond, and the bactenecin dimer appears to undergo
      multimeric oligomerization at high salt concentrations. Overall, dimeric
      bactenecin shows potent and rapid antimicrobial activity, and resists salt
      induced inactivation under physiological conditions through condensation and
      oligomerization. These characteristics shed light on the features that a peptide
      would need to serve as an effective therapeutic agent.

PMID- 18616464
TI  - In vitro stimulatory effect of anti-apoptotic seminal vesicle protein 4 on
      purified peroxidase enzymes.
AB  - The enzymatic activities of purified horseradish peroxidase, selenium-dependent
      glutathione peroxidase, thyroid peroxidase and myeloperoxidase, but not that of
      lactoperoxidase, were markedly enhanced when added into a reaction mixture
      containing 5 mum native seminal vesicle protein 4, a major protein secreted from
      rat seminal vesicle epithelium. A further increase of horseradish peroxidase
      activity was obtained using Ser58-phosphorylated or acetylated seminal vesicle
      protein 4. The activating effect of native seminal vesicle protein 4 was highest
      (about 60-fold) on horseradish peroxidase when 4-chloro-1-naphtol was used as the
      electron donor substrate. The main kinetics parameters of the stimulatory effect
      on horseradish peroxidase were evaluated and the enzyme-electron donor substrate
      interaction was investigated by HPLC and electrospray-MS. A native seminal
      vesicle protein 4/4-chloro-1-naphtol noncovalent adduct was detected when the
      protein and 4-chloro-1-naphtol were present in the appropriate molar ratio in the
      horseradish peroxidase-catalyzed reaction. By contrast, no adducts were formed
      between native seminal vesicle protein 4 and horseradish peroxidase. This native
      seminal vesicle protein 4/4-chloro-1-naphtol interaction might underlie the
      native seminal vesicle protein 4-induced horseradish peroxidase stimulation.
      Furthermore, native seminal vesicle protein 4 was shown by spectrophotometric and
      electrospray-MS analysis to interact with NADPH, an electron donor substrate of
      the selenium-dependent glutathione peroxidase/glutathione reductase redox system,
      with formation of an adduct between them. Although further investigation is
      required to elucidate the mechanism of adduct formation, this interaction,
      probably by promoting the release of the NADPH electrons required for glutathione
      disulphide reduction, could explain the stimulatory effect of seminal vesicle
      protein 4 on mammalian peroxidases possibly involved in its physiological
      function on the selenium-dependent glutathione peroxidase/glutathione reductase
      system. The biological significance of these properties of native seminal vesicle
      protein 4 might be related to its ability to downregulate reactive oxygen species
      and oxidative stress-induced apoptosis.

PMID- 18616465
TI  - Structure-guided alteration of coenzyme specificity of formate dehydrogenase by
      saturation mutagenesis to enable efficient utilization of NADP+.
AB  - Formate dehydrogenase from Candida boidinii (CboFDH) catalyses the oxidation of
      formate anion to carbon dioxide with concomitant reduction of NAD(+) to NADH.
      CboFDH is highly specific to NAD(+) and virtually fails to catalyze the reaction
      with NADP(+). Based on structural information for CboFDH, the loop region between
      beta-sheet 7 and alpha-helix 10 in the dinucleotide-binding fold was predicted as
      a principal determinant of coenzyme specificity. Sequence alignment with other
      formate dehydrogenases revealed two residues (Asp195 and Tyr196) that could
      account for the observed coenzyme specificity. Positions 195 and 196 were
      subjected to two rounds of site-saturation mutagenesis and screening and enabled
      the identification of a double mutant Asp195Gln/Tyr196His, which showed a more
      than 2 x 10(7)-fold improvement in overall catalytic efficiency with NADP(+) and
      a more than 900-fold decrease in the efficiency with NAD(+) as cofactors. The
      results demonstrate that the combined polar interactions and steric factors
      comprise the main structural determinants responsible for coenzyme specificity.
      The double mutant Asp195Gln/Tyr196His was tested for practical applicability in a
      cofactor recycling system composed of cytochrome P450 monooxygenase from Bacillus
      subtilis, (CYP102A2), NADP(+), formic acid and omega-(p-nitrophenyl)dodecanoic
      acid (12-pNCA). Using a 1250-fold excess of 12-pNCA over NADP(+) the first order
      rate constant was determined to be equal to k(obs) = 0.059 +/- 0.004 min(-1).

PMID- 18616466
TI  - Glutathione peroxidase family - an evolutionary overview.
AB  - Glutathione peroxidases (EC 1.11.1.9 and EC 1.11.1.12) catalyze the reduction of
      H(2)O(2) or organic hydroperoxides to water or corresponding alcohols using
      reduced glutathione. Some glutathione peroxidase isozymes have a selenium
      dependent glutathione peroxidase activity and present a selenocysteine encoded by
      the opal TGA codon. In the present study, insights into the evolution of the
      whole glutathione peroxidase gene family were obtained after a comprehensive
      phylogenetic analysis using the improved number of glutathione peroxidase
      sequences recorded in the PeroxiBase database (http://peroxidase.isb
      sib.ch/index.php). The identification of a common ancestral origin for the
      diverse glutathione peroxidase clusters was not possible. The complex
      relationships and evolutionary rates of this gene family suggest that basal
      glutathione peroxidase classes, present in all kingdoms, have originated from
      independent evolutionary events such as gene duplication, gene losses, lateral
      gene transfer among invertebrates and vertebrates or plants. In addition, the
      present study also emphasizes the possibility of some members being submitted to
      strong selective forces that probably dictated functional convergences of
      taxonomically distant groups.

PMID- 18616467
TI  - Binding of berberine to human telomeric quadruplex - spectroscopic, calorimetric
      and molecular modeling studies.
AB  - This study examines the characteristics of binding of berberine to the human
      telomeric d[AG(3)(T(2)AG(3))(3)] quadruplex. By employing UV-visible
      spectroscopy, fluorescence spectroscopy and isothermal titration calorimetry, we
      found that the binding affinity of berberine to the human telomeric quadruplex is
      10(6). The complete thermodynamic profile for berberine binding to the
      quadruplex, at 25 degrees C, shows a small negative enthalpy (DeltaH) of -1.7
      kcal.mol(-1), an entropy change with TDeltaS of +6.5 kcal.mol(-1), and an overall
      favorable free energy (DeltaG) of -8.2 kcal.mol(-1) . Through the temperature
      dependence of DeltaH, we obtained a heat capacity (DeltaC(p)) of -94 (+/- 5)
      cal.mol(-1).K(-1). The osmotic stress method revealed that there is an uptake of
      13 water molecules in the complex relative to the free reactants. Furthermore,
      the molecular modeling studies on different quadruplex-berberine complexes show
      that berberine stacking at the external G-quartet is mainly aided by the pi-pi
      interaction and the stabilization of the high negative charge density of O6 of
      guanines by the positively charged N7 of berberine. The theoretical heat capacity
      (DeltaC(p)) values for quadruplex-berberine models are -89 and -156 cal.mol(
      1).K(-1).

PMID- 18616468
TI  - Plant-pathogen interactions: what is proteomics telling us?
AB  - Over the years, several studies have been performed to analyse plant-pathogen
      interactions. Recently, functional genomic strategies, including proteomics and
      transcriptomics, have contributed to the effort of defining gene and protein
      function and expression profiles. Using these 'omic' approaches, pathogenicity-
      and defence-related genes and proteins expressed during phytopathogen infections
      have been identified and enormous datasets have been accumulated. However, the
      understanding of molecular plant-pathogen interactions is still an intriguing
      area of investigation. Proteomics has dramatically evolved in the pursuit of
      large-scale functional assignment of candidate proteins and, by using this
      approach, several proteins expressed during phytopathogenic interactions have
      been identified. In this review, we highlight the proteins expressed during plant
      virus, plant-bacterium, plant-fungus and plant-nematode interactions reported in
      proteomic studies, and discuss these findings considering the advantages and
      limitations of current proteomic tools.

PMID- 18616469
TI  - Synchronous Ca(2+) oscillation emerges from voltage fluctuations of Ca(2+)
      stores.
AB  - Synchronous Ca(2+) oscillation occurs in various cell types to regulate cellular
      functions. However, the mechanism for synchronization of Ca(2+) increases between
      cells remains unclear. Recently, synchronous oscillatory changes in the membrane
      potential of internal Ca(2+) stores were recorded using an organelle-specific
      voltage-sensitive dye [Yamashita et al. (2006) FEBS J273, 3585-3597], and an
      electrical coupling model of the synchronization of store potentials and Ca(2+)
      releases has been proposed [Yamashita (2006) FEBS Lett580, 4979-4983]. This model
      is based on capacitative coupling, by which transient voltage changes can be
      synchronized, but oscillatory slow potentials cannot be communicated. Another
      candidate mechanism is synchronization of action potentials and ensuing Ca(2+)
      influx through voltage-dependent Ca channels. The present study addresses the
      question of whether Ca(2+) increases are synchronized by action potentials, and
      how oscillatory store potentials are synchronized across the cells.
      Electrophysiological and Ca(2+)-sensitive fluorescence measurements in early
      embryonic chick retina showed that synchronous Ca(2+) oscillation was caused by
      releases of Ca(2+) from Ca(2+) stores without any evidence of action potentials
      in retinal neuroepithelial cells or newborn neurons. High-speed fluorescence
      measurement of store membrane potential surprisingly revealed that the
      synchronous oscillatory changes in the store potential were periodic repeats of a
      burst of high-frequency voltage fluctuations. The burst coincided with a Ca(2+)
      increase. The present study suggests that synchronization of Ca(2+) release is
      mediated by the high-frequency fluctuation in the store potential. Close
      apposition of the store membrane and plasma membrane in an epithelial structure
      would allow capacitative coupling across the cells.

PMID- 18616470
TI  - New insights into the functions and N-glycan structures of factor X activator
      from Russell's viper venom.
AB  - The coagulation factor X activator from Russell's viper venom (RVV-X) is a
      heterotrimeric glycoprotein. In this study, its three subunits were cloned and
      sequenced from the venom gland cDNAs of Daboia siamensis. The deduced heavy chain
      sequence contained a C-terminal extension with four additional residues to that
      published previously. Both light chains showed 77-81% identity to those of a
      homologous factor X activator from Vipera lebetina venom. Far-western analyses
      revealed that RVV-X could strongly bind protein S, in addition to factors X and
      IX. This might inactivate protein S and potentiate the disseminated intravascular
      coagulation syndrome elicited by Russell's viper envenomation. The N-glycans
      released from each subunit were profiled and sequenced by MALDI-MS and MS/MS
      analyses of the permethyl derivatives. All the glycans, one on each light chain
      and four on the heavy chain, showed a heterogeneous pattern, with a combination
      of variable terminal fucosylation and sialylation on multiantennary complex-type
      sugars. Amongst the notable features were the presence of terminal Lewis and
      sialyl-Lewis epitopes, as confirmed by western blotting analyses. As these glyco
      epitopes have specific receptors in the vascular system, they possibly contribute
      to the rapid homing of RVV-X to the vascular system, as supported by the
      observation that slower and fewer fibrinogen degradation products are released by
      desialylated RVV-X than by native RVV-X.

PMID- 18616471
TI  - Rhodanese-thioredoxin system and allyl sulfur compounds.
AB  - Sodium 2-propenyl thiosulfate, a water-soluble organo-sulfane sulfur compound
      isolated from garlic, induces apoptosis in a number of cancer cells. The
      molecular mechanism of action of sodium 2-propenyl thiosulfate has not been
      completely clarified. In this work we investigated, by in vivo and in vitro
      experiments, the effects of this compound on the expression and activity of
      rhodanese. Rhodanese is a protein belonging to a family of enzymes widely present
      in all phyla and reputed to play a number of distinct biological roles, such as
      cyanide detoxification, regeneration of iron-sulfur clusters and metabolism of
      sulfur sulfane compounds. The cytotoxic effects of sodium 2-propenyl thiosulfate
      on HuT 78 cells were evaluated by flow cytometry and DNA fragmentation and by
      monitoring the progressive formation of mobile lipids by NMR spectroscopy. Sodium
      2-propenyl thiosulfate was also found to induce inhibition of the
      sulfurtransferase activity in tumor cells. Interestingly, in vitro experiments
      using fluorescence spectroscopy, kinetic studies and MS analysis showed that
      sodium 2-propenyl thiosulfate was able to bind the sulfur-free form of the
      rhodanese, inhibiting its thiosulfate:cyanide-sulfurtransferase activity by
      thiolation of the catalytic cysteine. The activity of the enzyme was restored by
      thioredoxin in a concentration-dependent and time-dependent manner. Our results
      suggest an important involvement of the essential thioredoxin-thioredoxin
      reductase system in cancer cell cytotoxicity by organo-sulfane sulfur compounds
      and highlight the correlation between apoptosis induced by these compounds and
      the damage to the mitochondrial enzymes involved in the repair of the Fe-S
      cluster and in the detoxification system.

PMID- 18616473
TI  - Suicide in Australian veterinarians.

PMID- 18616474
TI  - Effect of intrauterine treatment with cephapirin on the reproductive performance
      of seasonally calving dairy cows at risk of endometritis following periparturient
      disease.
AB  - OBJECTIVE: To determine the effect of intrauterine cephapirin (0.5 g) treatment
      on the reproductive performance of cows diagnosed as at risk of developing
      endometritis. METHODS: Cows (n = 1325) from 17 seasonal calving dairy herds were
      enrolled if they had been calved for more than 6 days and had a condition that
      placed them at risk of endometritis. Half were treated with intrauterine
      cephapirin at an examination performed 28-37 days prior to mating start date
      (MSD). Cows were scored for body condition, their vaginal discharge was scored
      using vaginoscopy (VV), and the uterus and ovaries were assessed by rectal
      palpation. RESULTS: Overall, there was no significant treatment effect on
      reproductive performance. In 945 modified at risk (MAR) cows the effect of
      treatment varied with the calving to treatment interval (CTI) and VV status. For
      the subset of 229 MAR cows with CTI < or = 28 days, treatment improved the
      proportions of first-service conception (OR 3.1; P < 0.01) and 6-week in-calf (OR
      2.1; P < 0.05), and reduced the mean MSD to conception interval by 20 days (P <
      0.05). The difference was greater in cows with a positive VV score (1-3). Treated
      VV-negative cows with CTI > 48 days had a reduced proportion of cows in-calf by 6
      weeks (OR 0.58; P = 0.056) compared with untreated cows. CONCLUSION: Intrauterine
      cephapirin infusion of MAR cows improved reproductive performance, depending on
      CTI. The greater treatment effect in VV-positive cows suggests that VV scoring is
      a useful tool for the diagnosis of endometritis.

PMID- 18616475
TI  - Radiometric pooled faecal culture for the detection of Mycobacterium avium subsp
      paratuberculosis in low-shedder cattle.
AB  - OBJECTIVE: To identify the optimum pooling rate for pooled faecal culture (PFC)
      as a diagnostic tool in bovine Johne's disease control, for detection of cattle
      shedding low concentrations of Mycobacterium avium subsp paratuberculosis (Map).
      METHOD: Thirteen target animals were selected by delayed growth of Map from
      initial individual radiometric faecal cultures (first growth index at 5 weeks or
      later). A procedure based on radiometric culture and IS900 polymerase chain
      reaction and restriction endonuclease analysis confirmation was then used for
      PFC. RESULTS: Eight samples (stored for up to 17 months at -80 degrees C) yielded
      Map on subsequent culture, either from undiluted faeces or those mixed with
      normal cattle faeces at dilution rates from 1 in 5 to 1 in 50. From a regression
      equation, culture-positive animals were considered to be shedding relatively low
      levels of Map (< 6 x 10(4)/g of faeces). Pooling dilutions of more than 1 in 5
      reduced PFC sensitivity. A minimum incubation period of 10 weeks at a dilution of
      1 in 5 is recommended to detect such infected cattle. This pooling rate in
      radiometric culture is probably capable of detecting cattle shedding < or = 5 x
      10(3) Map organisms/g of faeces, representing an estimated inoculum per culture
      vial of fewer than 20 viable organisms. CONCLUSION: Map was detected in more than
      50% of the stored faecal samples from cattle shedding low concentrations of the
      organism. A pooling rate of 5 samples per pool is required to reliably detect
      infected low-shedder cattle using PFC based on radiometric culture.

PMID- 18616479
TI  - Surgical treatment of uterine torsion using a ventral midline laparotomy in 19
      mares.
AB  - OBJECTIVE: To report on the outcome of surgical treatment of uterine torsion in
      preterm mares. DESIGN: Retrospective case series of pregnant mares with uterine
      torsion presented to the Clinic for Obstetrics, Gynaecology and Andrology of
      Large and Small Animals. METHODS: Hospital records of all pregnant mares that
      underwent ventral midline laparotomy for uterine torsion between 1998 and 2004
      were reviewed. The signalment, history, clinical signs, results of diagnostic
      procedures, direction and degree of the uterine twist, treatment and outcome were
      retrieved from each case record. RESULTS: This study comprised 19 mares between
      months 5 and 11 of pregnancy (8.7 +/- 1.9) and suffering from uterine torsion. In
      all cases ventromedian laparotomy was carried out under general anaesthesia.
      Gastrointestinal disorders were also present in 52.6% of horses. Postoperative
      complications included subcutaneous seromas (five mares), peritonitis (one mare)
      and abortion (two mares). In four mares (21%) the operation was unsuccessful
      (i.e. these mares had to be euthanased intra- or postoperatively). Of the
      surviving 15 mares, 13 (86.6%) gave birth to viable foals at full term. The foals
      developed normally. Only two mares aborted. CONCLUSIONS: Because of its
      versatility the ventral midline approach should be considered for correction of
      uterine torsion. The approach has many advantages, including rapid and clear
      access to the abdominal cavity, safety, visual assessment of uterine wall
      viability, correction of concomitant gastrointestinal tract problems, and
      performance of hysterotomy or hysterectomy, if indicated. In this study, managing
      uterine torsion in this way resulted in a high percentage of cases (86.6%) in
      which pregnancy was maintained, with the birth of a viable, mature foal.

PMID- 18616477
TI  - Blood culture isolates and antimicrobial sensitivities from 427 critically ill
      neonatal foals.
AB  - OBJECTIVE: To assist correct decision-making about antimicrobial treatment of
      equine neonates with septicaemia. DESIGN: Retrospective study of microbial blood
      culture results obtained from foals less than 7 days of age. METHODS: Microbial
      blood culture results from foals less than 7 days of age admitted to an intensive
      care unit between July 1999 and December 2004 were reviewed. Antimicrobial
      sensitivity was assessed by the Kirby Bauer disc diffusion method. Antimicrobials
      were defined as an effective first-line choice antimicrobial if greater than 70%
      of isolates were susceptible. Multiple drug resistance (MDR) was defined as
      resistance to at least three antimicrobials in different chemical classes or with
      different mechanisms of resistance. RESULTS: Of the 427 Thoroughbred foals
      included in the study, a positive blood culture was obtained in 110 foals and 124
      microorganisms were isolated. Gram-positive isolates, predominantly
      Streptococcus/Enterococcus spp, were obtained in 41% of foals. Gram-negative
      isolates were predominantly of the Enterobacteriaceae family, in particular
      Escherichia coli. The overall antimicrobial sensitivity of the isolates was low.
      The Gram-positive organisms had unpredictable sensitivity patterns. MDR was
      recorded in 32% of isolates. In total, 81% of foals were discharged from hospital
      and 74.5% of foals with a positive blood culture were discharged. CONCLUSION:
      With the increasing prevalence of Gram-positive microorganisms and their
      unpredictable sensitivity patterns, blood cultures remain important in the
      diagnosis and treatment of equine neonatal septicaemia.

PMID- 18616480
TI  - Bronchitis associated with Tracheomyia macropi in a red-necked wallaby (Macropus
      rufogriseus).

PMID- 18616481
TI  - Quantification of VEGF-C expression in canine mammary tumours.
AB  - BACKGROUND: Tumours release angiogenic factors such as vascular endothelium
      growth factor (VEGF), which induces growth of a capillary network around the
      tumour. Elevated concentrations of VEGF have been reported in human mammary gland
      tumours. METHODS: To evaluate the expression of VEGF-C mRNA in canine mammary
      tissue, 38 mammary gland tumours (including 15 benign and 23 malignant mammary
      tumours), and 4 normal mammary glands were investigated by real-time reverse
      transcriptase quantitative polymerase chain reaction. RESULTS: VEGF-C expression
      in the malignant mammary tumours was much higher than in the benign mammary
      tumours or normal mammary tissue (P < 0.001). The expression of VEGF-C in tumours
      with lymph node metastasis was much higher than in those without (P < 0.01).
      CONCLUSION: The level of expression of VEGF-C did not correlate with tumour size
      or the patient's age, but was significantly higher in malignant mammary tumours
      and related to lymph node metastasis, making it a candidate marker for predicting
      metastasis of canine mammary cancer.

PMID- 18616482
TI  - Number, distribution and concentration of Australian veterinarians in 2006,
      compared with 1981, 1991 and 2001.
AB  - OBJECTIVE: To determine the number, concentration and distribution of
      veterinarians working in Australia in 2006, and compare with data from 1981, 1991
      and 2001. Procedure Data on each veterinarian who was registered, resident and
      apparently working in each Australian state and territory were obtained from
      relevant veterinary board lists, entered into an Excel spreadsheet and analysed
      with SAS System for Windows 8. Other data were obtained from the Official
      Australian Postcode Map, and the Australian Bureau of Statistics. RESULTS: A
      total of 7510 veterinarians, of whom 46% were female, were working in Australia
      in 2006. The rate of increase (230/year) between 2001 and 2006 was greater than
      for the previous 20 years. The number per million people (360) was 73% higher
      than in 1981, and more than 30% higher than in the USA and UK. With the
      establishment of three new veterinary schools the number of graduates, and the
      total number of veterinarians, will increase further. By 2011 the number of
      veterinarians is likely to be three-fold greater, and the number per million
      people two-fold greater than in 1981. The number of veterinarians per million
      dogs and cats will increase at a greater rate if dog and cat numbers continue to
      fall. As more than 75% of Australian veterinary work involves dogs and cats this
      has serious implications for the profession. CONCLUSIONS: Progressively
      increasing numbers of veterinarians will compete for a constant or diminishing
      resource--the dogs and cats of Australia. It seems likely that overt signs of
      oversupply will appear before sufficient numbers of veterinarians enter
      alternative forms of employment.

PMID- 18616484
TI  - [Monophasic dermal filler based on hyaluronic acid: a new era of tissue
      augmentation--introduction to the topic].

PMID- 18616485
TI  - [Tissue augmentation with hyaluronic acid fillers--practical procedure].

PMID- 18616486
TI  - [Augmentation with a monophasic dermal filler--case reports from the study].

PMID- 18616487
TI  - [Minimally invasive combination treatments--proven strategy for a harmonious
      total esthetic picture].

PMID- 18616488
TI  - [Hyaluronic acid in esthetic medicine--history, development, current
      significance].

PMID- 18616489
TI  - [Hyaluronic acid filler for correction of nasolabial grooves--results of a
      clinical study].

PMID- 18616490
TI  - Vasopressin in paediatric practice.

PMID- 18616491
TI  - Determining the accuracy of caudal needle placement in children: a comparison of
      the swoosh test and ultrasonography.
AB  - BACKGROUND: The aim of the present study was to compare two confirmatory tests -
      the 'swoosh' test (auscultation during caudal injection) and real time ultrasound
      imaging (both transverse 2D imaging and color flow Doppler imaging) in pediatric
      patients receiving a caudal epidural block. METHODS/MATERIALS: This was a
      retrospective observational study of caudal injections administered to 83
      pediatric patients (0-11 years) presenting for elective surgery over a 4 month
      time period. While injecting small aliquots of local anesthetic, a standard
      stethoscope was placed over the lower lumbar spine to auscultate for the 'swoosh'
      test. An ultrasound machine (Sonosite Titan, Sonosite Inc., Bothell, WA, USA) was
      then utilized for real-time visualization of caudal injectate. Each test
      performed during the caudal injection (swoosh, turbulence on 2D imaging, or color
      flow on Doppler imaging) was recorded as positive, negative or equivocal.
      RESULTS: Eighty out of 83 patients (96.4%) had a successful caudal block based on
      minimal or no perioperative narcotic use, minimal or no response to surgical
      stimulation, the presence of motor blockade and patient comfort in the PACU.
      Ultrasound was significantly superior to 'swoosh' for sensitivity (96.3% vs
      57.5%), negative predictive (40% vs 5.6 value) % and likelihood ratio (2.89 vs
      1.73). Specificity and positive predictive value were not different between
      'swoosh' and ultrasound. Of the ultrasound tests, turbulence was more sensitive
      than color flow Doppler (95.0% vs 78.8%). CONCLUSION: Ultrasonography is superior
      to the 'swoosh' test as an objective confirmatory technique during caudal block
      placement in children. We found the presence or absence of turbulence during
      injection within the caudal space to be the best single indicator of caudal
      success. We think ultrasonography should be used, if available, when teaching
      this technique.

PMID- 18616492
TI  - Premedication with melatonin vs midazolam in anxious children.
AB  - AIM: Failure of dental treatment caused by anxiety is a common problem in
      children. Oral midazolam has been the most commonly used premedication for
      pediatric patient but the use of midazolam may be associated with paradoxical
      reactions in children. Melatonin may induce a natural sleepiness and improve
      sedation. We have investigated premedication with melatonin compared with
      midazolam in children under nitrous oxide/oxygen (N(2)O/O(2)) sedation for dental
      treatment. METHODS: In a randomized study, 60 children received either 3 mg of
      melatonin [Melatonina (3 mg(R)) 60 min before the procedure (n = 15); group I],
      0.5 mg.kg(-1) melatonin 60 min before the procedure (n = 15; group II), 0.75
      mg.kg(-1) midazolam [Dormicum (15 mg/3 ml (R)) 15 min before the procedure (n =
      15); group III] or 3 ml of 0.09 NaCl 15 min (n = 7) or 60 min before the
      procedure (n = 8; group IV) orally. The children were sedated with 40/60%
      N(2)O/O(2) inhalation. The heart rate and O(2) saturation were monitored during
      the treatment period. The level of sedation was assessed according to the Ramsay
      Sedation Scale. The children's sedation success during dental treatment was
      classified. The sedation success and other sedation-related events recorded.
      Comparisons among the four groups were made using one-way anova or Kruskal-Wallis
      test, and if any significant differences were noted, the Tukey's HSD or Mann
      Whitney U-test were used for intergroup comparisons. All differences were
      considered significant at P < 0.05. RESULTS: The evaluation of sedation success
      was as follows: group I: satisfactory (n = 1), average satisfactory (n = 4), and
      unsatisfactory (n = 10); group II: satisfactory (n = 2), average satisfactory (n
      = 3), and unsatisfactory (n = 10); group III: satisfactory (n = 9), average
      satisfactory (n = 6); and group IV: satisfactory (n = 1), average satisfactory (n
      = 3), and unsatisfactory (n = 11). CONCLUSION: In these doses and clinical
      conditions, melatonin was similar to that of placebo and did not contribute to
      N(2)O/O(2) sedation of anxious children.

PMID- 18616493
TI  - Intra-arterial access in pediatric patients.

PMID- 18616494
TI  - Spontaneous liver hemorrhage during laparotomy in a preterm infant.

PMID- 18616495
TI  - Myocarditis and anesthesia.

PMID- 18616496
TI  - Anesthetic management of a patient with Seckel syndrome and implanted pacemaker.

PMID- 18616497
TI  - In the vein but in vain.

PMID- 18616498
TI  - Unexpected vomiting during anesthesia induction in a patient with undiagnosed
      congenital esophageal stenosis.

PMID- 18616499
TI  - Difficult proseal laryngeal mask airway placement in a child: made easy by bougie
      guided technique.

PMID- 18616500
TI  - Did opioid sensitivity contribute to post-tonsillectomy arrest?

PMID- 18616501
TI  - Combined monitored anesthesia care and femoral nerve block for muscle biopsy in
      children with myopathies.

PMID- 18616504
TI  - The paradoxical image of chemotherapy: a phenomenological description of nurses'
      experiences of administering chemotherapy.
AB  - The paradoxical image of chemotherapy: a phenomenological description of nurses'
      experiences of administering chemotherapyA sample of nine nurses who were
      employed within a haematology ward, a bone marrow transplant unit and a
      chemotherapy outpatient department of a single hospital Trust in the UK, and who
      regularly administered cytotoxic chemotherapy were recruited to participate in
      the study. A qualitative phenomenological design was used with a semi-structured
      interview format. The findings revealed a 'Paradoxical image of chemotherapy'
      that was related to the overall damaging effects of chemotherapy where it both
      serves as a curative treatment and 'another chance of life' and also causes
      damage (morbidity) while it cures. The nurses administering chemotherapy were
      found to also experience 'damage' as a result of seeing the suffering of their
      patients and being involved in dilemmas regarding administering chemotherapy
      treatments. The patient experiences are described from the nurses' perspective.

PMID- 18616505
TI  - Basaloid carcinoma of the prostate: a case report and review of the literature.
AB  - Malignant tumours arising from the basal cells of the prostate gland are
      extremely rare, and the majority of reports in the literature suggest a
      relatively indolent clinical course. We report a case of infiltrative basaloid
      carcinoma of the prostate in a 68-year old man that did not respond to systemic
      chemotherapy. It is essential that this aggressive disease is differentiated from
      more indolent basaloid proliferations, as metastatic spread can occur and outcome
      may be poor.

PMID- 18616506
TI  - Prospective analysis of the long-term effect of teaching breast self-examination
      and breast awareness.
AB  - Breast cancer is the most common cancer in women in the industrialized world and
      a leading cause of death. Breast self-examination (BSE) is one of the methods for
      an early detection of breast cancer. In the present study the effectiveness of a
      campaign promoting BSE and breast awareness was analysed. Seminars were conducted
      in 2003 in Lower Saxony, Germany by a female gynaecologist and a social pedagogue
      and included a lecture, an individual training in BSE in a separate room and a
      talk about the importance of regular BSEs. Questionnaires were handed out
      immediately after the seminar and were sent by post 1 year later. Attendance of
      the seminar resulted in a significantly higher percentage of monthly BSEs (21.4%
      before vs. 61.9% after the teaching). Furthermore, 92.1% of the women who did not
      perform a monthly BSE stated that at least they examined their breasts more
      frequently after attending the seminar. The data demonstrate that the seminars in
      BSE had profound effects on the compliance of women in carrying out BSE regularly
      and correctly, without influence of age or education.

PMID- 18616507
TI  - Accumulation of MYH9 mRNA at leukocyte inclusion bodies in MYH9 disorders.

PMID- 18616509
TI  - Capillary gel electrophoresis: a simple method for identification of mutations
      and polymorphisms in the CEBPA gene in patients with acute myeloid leukaemia.
AB  - INTRODUCTION: The CEBPA gene encodes a transcription factor, CCAAT/enhancer
      binding protein (C/EBP)alpha. Expression of the wildtype protein is essential for
      the lineage specific differentiation of myelocytic haematopoietic precursors into
      mature neutrophils. Eight percentage of all AML patients harbour at least one
      mutation in this gene, increasing up to 15% in the group, where standard
      karyotypic analysis do not reveal chromosomal aberrations. OBJECTIVE: We designed
      a method, which discriminates as little as single base insertions or deletions
      accounting for 90% of all CEBPA mutations. The TAD2C length polymorphism was also
      identified using this set up. PATIENTS AND METHODS: Diagnostic bone marrow or
      peripheral blood from 446 adults and 39 children diagnosed with AML from 1980 to
      2006 was analysed for mutations by PCR and capillary gel electrophoresis.
      RESULTS: We analysed pretreatment samples from 485 AML patients and 57 healthy
      volunteers and identified sequence variations in 35/446 adults and 1/39 children.
      We were immediately able to distinguish N- and C-terminal insertions and
      deletions as well as normally occurring polymorphisms. Abnormal PCR products were
      reprocessed and analysed by direct sequencing. We found stringent accordance
      between the two methods and reached the same frequency of mutations and
      polymorphisms as known from the literature. CONCLUSION: We conclude that
      capillary gel electrophoresis can be used as an accurate and high throughput
      diagnostic procedure for mutational status in the CEBPA gene identifying not only
      the same mutational frequency as in the published reports but also the TAD2C
      polymorphism in addition.

PMID- 18616510
TI  - Homoharringtonine affects the JAK2-STAT5 signal pathway through alteration of
      protein tyrosine kinase phosphorylation in acute myeloid leukemia cells.
AB  - OBJECTIVES: Homoharringtonine (HHT) was efficient in therapying patients with
      acute myeloid leukemia (AML) in China, but little is known about the mechanism of
      its action. As the abnormal activation of JAK2 associated pathway is important to
      AML, we try to explore the effect of HHT on JAK2-STAT pathway in AML cells, thus
      supplying theoretical basis for wider use of HHT. METHODS: The cell viability was
      tested by MTT. Apoptosis was tested by flow cytometry. RT-PCR was used to measure
      the expression of JAK2, STAT5 and the effect gene Bcl-xL. The signal proteins
      such as p-JAK2, p-STAT5, p-AKT, p-ERK activated by abnormal activated JAK2 were
      tested by Western blotting. RESULTS: HHT obviously inhibited the viability of
      primary AML cells and AML cell lines HEL, K562 and HL-60 cells, AnnexinV-PI
      double staining confirmed early apoptosis in a dose-dependent manner. In
      immunoblotting analysis, when AML cells were affected by HHT for 6 h (much ahead
      of the time when apoptosis could be induced). The expressions of p-JAK2, p-STAT5,
      and p-AKT were down-regulated, while the total JAK2, STAT5 and AKT protein levels
      were stable. There were no changes in p-ERK and BcL-xL proteins. When it
      prolonged to 24 h, Bcl-xL decreased obviously. Similar results were obtained by
      using JAK2 specific inhibitor AG490. CONCLUSIONS: HHT possibly acts as a broad
      spectrum PTK inhibitor and inhibits the phosphorylation of the signal proteins
      caused by oncogenic proteins such as JAK2V617F, BCR/ABL, thus blocking the
      survival and proliferative signal pathway of malignant cells.

PMID- 18616511
TI  - Hematopoietic progenitor cell colony growth differentiates chronic myelomonocytic
      leukemia from reactive monocytosis.
AB  - In the absence of a cytogenetic abnormality or overt dysplasia, chronic
      myelomonocytic leukemia (CMML) may be difficult to be distinguished from reactive
      monocytosis. We have previously described a typical growth pattern in CMML
      patients, i.e., 'pseudonormal' colonies resembling granulocytic colonies but
      consisting entirely of monocytic cells when stained. To study the utility of the
      colony forming unit cell assay (CFU-C) as a diagnostic tool in patients with
      monocytosis, we analyzed a cohort of 48 consecutive patients referred to our
      institution with peripheral blood monocytosis. Thirty-six patients fulfilled the
      WHO criteria for CMML; 12 were diagnosed with reactive monocytosis. Of the
      patients with CMML, 28 showed pseudonormal growth with or without leukemic
      cluster growth, another four showed exclusively leukemic growth. None of the
      patients with reactive monocytosis showed either leukemic or pseudonormal growth.
      With a specificity of 100% and a sensitivity of 89%, the CFU-C assay has a unique
      potential to distinguish CMML from reactive monocytosis.

PMID- 18616512
TI  - Disease burden of chronic lymphocytic leukaemia within the European Union.
AB  - OBJECTIVE: Whilst Chronic lymphocytic leukaemia (CLL) is considered a rare
      disease, to our knowledge, the current prevalence of CLL within the European
      Union (EU) member states is not published. Understanding the number of
      individuals with CLL is vital to assess disease burden within the wider
      population. METHODS: Using 2002 data from the International Agency for Research
      on Cancer, we estimated the number of individuals with CLL (ICD-10 C91.1) from
      those reported for all leukaemias (C91-95) and extrapolated the figures by the
      population increase within the EU between 2002 and 2006, the last year with fully
      updated community population estimates. One- and 5-yr partial prevalence
      estimates are reported (i.e. the number of individuals still living 1-5 yr post
      diagnosis). We then applied proportional estimates from the literature to assess
      those requiring immediate treatment, those under observation and their likely
      progression rates. RESULTS: We found that within the 27 EU states plus Iceland,
      Norway and Lichtenstein, 1- and 5-yr CLL partial prevalence estimates totalled
      approximately 13,952 and 46,633 individuals respectively in 2006. By applying
      Binet staging to the 1-yr estimate, 40% of patients will be stage B/C and require
      immediate treatment. Thus, 5581 individuals may be treated within the first year
      of diagnosis. Of the 60% (8371) under observation, by 5 yr up to 33% (2763) may
      have more advanced disease with increased risk of mortality. CONCLUSION: Whilst
      CLL is a rare disease, the number of individuals burdened by the disease within
      the EU is considerable and thousands of patients require treatment and physician
      care, which has cost implications for member states.

PMID- 18616513
TI  - Prognostic significance of p53 and matrix metalloproteinase-9 expression in
      follicular lymphoma.
AB  - OBJECTIVES: p53 mutations and high protein expression are associated with adverse
      prognosis in several lymphoma subtypes. Matrix metalloproteinase-9 (MMP-9) has
      also been found to correlate with poor survival in all lymphomas studied. The
      data concerning the clinical role of protein expression of p53 or gelatinases and
      their inhibitors in follicular lymphoma are rare. The purpose of this study was
      to evaluate the prognostic and clinical implications of the immunoreactive
      proteins p53, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP
      1) and TIMP-2 in follicular lymphoma. METHODS: The material consisted of 67
      patients with primarily non-transformed follicular lymphoma. Diagnostic lymph
      node tissue sections of patients were stained by immunohistochemical method using
      specific monoclonal antibodies. RESULTS: p53 over-expression was detected in 8
      (12%) out of 67 cases. p53 over-expression correlated with high grade (P =
      0.011), bulky tumour (P = 0.031) and forthcoming transformation (P = 0.001). It
      also correlated with poor overall (P = 0.001) and cause-specific survival (P =
      0.010) in multivariate analysis and had a strong inverse correlation with time to
      transformation (P < 0.001). MMP-2, MMP-9 and TIMP-2 expression correlated with
      high grade. MMP-9 positivity in centroblasts correlated with good chemotherapy
      response (P = 0.019), but it was not prognostic for survival. MMP-2, TIMP-1 or
      TIMP-2 did not associate with survival, either. CONCLUSIONS: In this study, p53
      over-expression predicted both transformation to diffuse large B-cell lymphoma
      and poorer overall and cause-specific survival of patients with follicular
      lymphoma. Expression of gelatinases or their inhibitors did not have any
      significant correlations with prognosis, although MMP-9 predicted a good response
      to first-line chemotherapy.

PMID- 18616514
TI  - Myocardial infarction in thrombotic thrombocytopenic purpura: a single-center
      experience and literature review.
AB  - BACKGROUND: Several case reports and series have described myocardial infarctions
      (MIs) in patients hospitalized for thrombotic thrombocytopenic purpura (TTP). The
      exact magnitude and outcome of this complication are unknown. METHODS: Electronic
      medical records for patients admitted to Wake Forest University Baptist Medical
      Center were examined from 1996 to 2005. Those patients having a diagnosis of TTP
      during the hospitalization period were included in the analysis. Only patients'
      initial episodes of TTP were analyzed. Baseline cardiac and TTP risk factors were
      documented. Outcomes analyzed included MIs, arrhythmias, development of
      congestive heart failure and death. RESULTS: Eighty-five patients diagnosed with
      TTP were identified with 13 (15.3%) having MIs, as defined by an elevation of
      cardiac enzymes. Median troponin I value was 5.9 ng/mL (range 3.7-8.8 ng/mL).
      Twelve patients had non-ST segment elevation MIs and one had ST segment
      elevation. Two of 13 patients who had echocardiographic analysis had documented
      wall motion abnormalities. There was no difference between non-MI and MI patients
      in cardiac risk factors, prior cardiac events, history of thromboembolic disease
      or heart failure. There was no in-hospital mortality difference. CONCLUSION: MI
      is an important complication of TTP, identified in 15.3% of patients in our
      study. Routine cardiovascular evaluation with cardiac enzymes,
      electrocardiography, and telemetry is warranted in acute TTP patients.
      Appropriate intervention is yet to be determined.

PMID- 18616515
TI  - Successful treatment of a patient with lymphocyte-predominant Hodgkin's lymphoma
      with yttrium-90-ibritumomab tiuxetan.
AB  - Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is known to be radiosensitive,
      and radiotherapy often forms part of the treatment of patients with stage III or
      IV LPHL. In addition, as LPHL is thought to arise from a germinal centre B-cell,
      and LPHL cells express the B-cell marker CD20 there is a rationale for using anti
      CD20 therapies for the treatment of LPHL. We report a 42-yr-old man with stage
      III B LPLH who underwent successful treatment of LPHL with (90)Y-ibritumomab
      tiuxetan. To our knowledge, this is the first report on the use of an anti-CD20
      radiolabeled antibody for the treatment of LPHL.

PMID- 18616516
TI  - Clinical trial: Radiofrequency energy delivery in proton pump inhibitor-dependent
      gastro-oesophageal reflux disease patients.
AB  - BACKGROUND: Radiofrequency (RF) energy delivery is an endoscopic procedure
      developed for the treatment of gastro-oesophageal reflux disease. AIM: To compare
      RF and a proton pump inhibitor strategy (PPI) in PPI-dependent patients by
      carrying out a prospective, randomized trial. METHODS: Patients with PPI
      dependent typical reflux symptoms were randomly allocated to either RF or PPI
      regimen alone. The primary endpoint, evaluated at 6-month, was defined as the
      possibility for the patient to stop or to decrease PPI use to <50% of the
      effective dose required at baseline. RESULTS: In the RF group, 18/20 patients
      stopped (n = 3) or decreased (n = 15) PPI use as compared to eight of 16 in the
      PPI group (P = 0.01). None of the control patients could stop PPI. Health-related
      quality of life scores were not different between groups. No significant change
      in oesophageal acid exposure (OAE) was noted between baseline and 6-months after
      RF. No severe complication was reported. CONCLUSIONS: Radiofrequency energy
      delivery is a safe and effective therapeutic option, allowing reduction in or
      discontinuation of PPI therapy in patients with PPI-dependent symptoms, without
      loss of quality of life. However, in a majority of patients, PPI therapy cannot
      be completely stopped. The efficacy of RF does not seem to be related to a
      decrease in OAE.

PMID- 18616518
TI  - Prospective evaluation of the pharmacogenetics of azathioprine in the treatment
      of inflammatory bowel disease.
AB  - AIM: To investigate whether pharmacogenetic loci or metabolite concentrations
      explain clinical response or side effects to AZA. METHODS: Patients with IBD were
      given 2 mg/kg of AZA without dose escalation or adjustment. Serial clinical
      response, thiopurine methyl transferase (TPMT) activity and thioguanine
      nucleotide (TGN) concentrations were measured over 6 months. All patients were
      genotyped for inosine triphosphatase (ITPase) and TPMT. Clinical response and
      side effects were compared to these variables. RESULTS: Two hundred and seven
      patients were analysed. Thirty-nine per cent withdrew due to adverse effects.
      Heterozygous TPMT genotype strongly predicted adverse effects (79% heterozygous
      vs. 35% wild-type TPMT, P < 0.001). The ITPA 94C>A mutation was associated with
      withdrawal due to flu-like symptoms (P = 0.014). A baseline TPMT activity below
      35 pmol/h/mg/Hb was associated with a greater chance of clinical response
      compared with a TPMT above 35 pmo/h/mg/Hb (81% vs. 43% respectively, P < 0.001).
      Patients achieving a mean TGN level above 100 were significantly more likely to
      respond (P = 0.0017). CONCLUSIONS: TPMT testing predicts adverse effects and
      reduced chance of clinical response (TPMT >35 pmol/h/mg/Hb). ITPase deficiency is
      a predictor of adverse effects and TGN concentrations above 100 correlate with
      clinical response.

PMID- 18616521
TI  - Evaluation of the size 4 i-gel airway in one hundred non-paralysed patients.
AB  - We studied the i-gel in 100 elective, anaesthetised patients (55:45 male:female,
      median age 53 years) assessing: ease of use, airway quality, positioning, seal
      and complications. First insertion attempt was successful in 86 patients, second
      attempt in 11 patients, and third attempt in three patients. Fifty three
      manipulations were required in 26 patients (median 1) to achieve a clear airway.
      Median insertion time was 15 s. During ventilation, expired tidal volume of 7 ml
      x kg(-1) was achieved in 96 (96%) patients. Median airway leak pressure was 24
      cmH(2)O. On fibreoptic examination via the device, vocal cords were visible in 87
      patients (91%). During maintenance, six patients (6%) required 12 airway
      manipulations. There was one episode of regurgitation, without aspiration. Other
      complications and patient side-effects were mild and few. The i-gel is easily and
      rapidly inserted, providing a reliable airway in over 90% of cases. Further
      studies are indicated to assess safety and performance compared to other
      supraglottic airway devices.

PMID- 18616522
TI  - Effects of fentanyl pretreatment on the QTc interval during propofol induction.
AB  - Prolongation of the corrected QT (QTc) interval is associated with various
      anaesthetic drugs. The QTc prolongation may become more exacerbated during
      laryngoscopy and intubation, which is possibly caused by sympathetic stimulation.
      The aim of this study was to investigate the effects of fentanyl on the QTc
      interval during propofol induction in healthy patients. The patients were
      randomly allocated to receive either fentanyl (n = 25) or saline (n = 25) before
      induction. The QTc interval was significantly prolonged immediately after
      intubation in control group compared to preceding values, but it did not change
      in the fentanyl group. The number of patients with the prolonged QTc interval
      exceeding 20 ms immediately after intubation compared to the baseline values was
      14 in the control group and seven in the fentanyl group. In conclusion,
      pretreatment with fentanyl 2 microg x kg(-1) significantly attenuated QTc
      prolongation associated with laryngoscopy and tracheal intubation during propofol
      induction.

PMID- 18616523
TI  - An evaluation of conscious sedation using propofol and remifentanil for tension
      free vaginal tape insertion.
AB  - Tension-free vaginal tape insertion is a recommended treatment for stress
      incontinence. There is evidence that intra-operative testing of continence by
      asking patients to cough may improve outcomes, but an optimal sedation regimen
      has not been determined. We prospectively evaluated the effectiveness of propofol
      and remifentanil infusions in 25 patients using pre- and post-sedation peak cough
      pressures and pain scores. Patient satisfaction was assessed using the Iowa
      Satisfaction with Anaesthesia Score (ISAS). Post-sedation cough pressures were
      improved compared to baseline, with a mean peak pressure increase of 24 mmHg (95%
      CI 15.5-32.5; p < 0.001). Pain scores (median, IQR [range]) were low for local
      anaesthetic infiltration (0, [0-1]) and first (0, [0-1]) and second (0, [0-3.5])
      needle insertions. Of the 19 patients completing the ISAS, all felt safe and
      satisfied. Sedation using propofol and remifentanil provides acceptable
      analgesia, satisfaction and effective continence testing.

PMID- 18616524
TI  - Purple corn color suppresses Ras protein level and inhibits 7,12
      dimethylbenz[a]anthracene-induced mammary carcinogenesis in the rat.
AB  - Anthocyanins belong to the class of phenolic compounds collectively named
      flavonoids. Many anthocyanins are reported to have inhibitory effects on
      carcinogenesis. Purple corn color (PCC), an anthocyanin containing extract of
      purple corn seeds, is used as a food colorant. The major anthocyanin in PCC is
      cyanidin 3-O-beta-D-glucoside (C3-G). The present study was conducted to assess
      the influence of dietary PCC on 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      mammary carcinogenesis in rats. PCC significantly inhibited DMBA-induced mammary
      carcinogenesis in human c-Ha-ras proto-oncogene transgenic (Hras128) rats and in
      their non-transgenic counterparts. PCC and C3-G also inhibited cell viability and
      induced apoptosis in mammary tumor cells derived from Hras128 rat mammary
      carcinomas. At the molecular level, PCC and C3-G treatment resulted in a
      preferential activation of caspase-3 and reduction of Ras protein levels in tumor
      cells. It is proposed that C3-G could act as a chemopreventive and possibly
      chemotherapeutic agent for cancers with mutations in ras. Secondly, the in vitro
      in vivo system used in this study can be utilized for screening for cancer
      preventive compounds that act via Ras down-regulation.

PMID- 18616525
TI  - Periodic analysis of urethane-induced pulmonary tumors in living A/J mice by
      respiration-gated X-ray microcomputed tomography.
AB  - X-ray microcomputed tomography (micro-CT) with a respiratory gating system is a
      useful non-invasive approach to evaluate lung tumor development in living animal
      models. Here micro-CT was applied for the detection of lung lesions induced by a
      single intraperitoneal injection (250 mg/kg) of urethane in male A/J mice, at 2
      week intervals from 10 to 30 weeks after carcinogen exposure. In micro-CT cross
      sections, lung tumor images were easily distinguished from surrounding non
      tumorous tissues, the smallest detected tumor being approximately 0.5 mm in
      diameter. All of the urethane-treated mice (n = 15) developed lung tumors and the
      number of tumors developed in each mouse was 8.6 +/- 3.9. Six tumors, determined
      histopathologically to be adenocarcinomas, were detected, growing at different
      rates during the experimental period. The most aggressive carcinoma, increasing
      in diameter from 0.9 to 3.5 mm within 8 weeks, was a solid-type nodule with a
      clear tumor margin on the micro-CT imaging. Other tumors, histopathologically
      adenomas, grew slowly or moderately. The results provide evidence that micro-CT
      is a useful non-invasive imaging approach for evaluating the characteristics and
      growth of lung tumors in mice.

PMID- 18616526
TI  - High mobility group box-1-inducible melanoma inhibitory activity is associated
      with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma.
AB  - Melanoma inhibitory activity (MIA) is an 11-kDa secretory protein isolated from
      malignant melanoma cells that is correlated with invasion and metastasis in
      various human malignancies. We examined MIA expression in 62 oral squamous cell
      carcinomas (OSCC) by immunohistochemistry. MIA expression was significantly
      associated with nodal metastasis (P = 0.00018). MIA expression was also
      associated with expression of high mobility group box-1 (HMGB1) (P < 0.0001) and
      lymph vessel density (P < 0.0001). Expression levels of MIA, HMGB1, nuclear
      factor kB (NFkB) p65 and HMGB1-NFkB p65 binding were significantly higher in a
      metastatic human OSCC cell line (HSC3) than those in a non-metastatic OSCC cell
      line (HSC4). Treatment with receptor for advanced glycation end products (RAGE)
      antisense or small interfering RNA and human recombinant HMGB1 (hrHMGB1) did not
      affect MIA expression, whereas HMGB1 antisense or siRNA treatment decreased MIA
      expression in HSC3 cells. Then HMGB1 enhanced MIA expression as an NFkB cofactor
      but not as a RAGE ligand. MIA neutralization by MIA antibodies increased
      extracellular signal-related kinase 1/2 phosphorylation, but decreased p38
      phosphorylation and the expression of vascular epithelial growth factor (VEGF)-C
      and -D. Treatment with p38 inihibitor decreased VEGF-C and -D expression in HSC3
      cells. These results suggest that MIA expression is enhanced by the interaction
      of intracellular HMGB1 and NFkBp65 and MIA is closely involved in tumor
      progression and nodal metastasis by the increments of VEGF-C and VEGF-D in OSCC.

PMID- 18616527
TI  - Reactive oxygen species-mediated cyclin D1 degradation mediates tumor growth
      retardation in hypoxia, independently of p21cip1 and hypoxia-inducible factor.
AB  - Cell growth arrest is an adaptation process for tumor survival in hypoxic
      environments. As proliferation is a very complicated and dynamic process, hypoxic
      growth arrest is not considered to be simply determined by a few molecules.
      Recently, several research groups have demonstrated that hypoxia-inducible factor
      (HIF)-1alpha plays a crucial role in hypoxia-induced cell-cycle arrest by
      inhibiting c-Myc and subsequently inducing p21(cip1) expression. However, we
      found that hypoxic growth arrest could occur even in p21-null cancer cells, and
      addressed the p21-independent process of cell-cycle arrest. We show that cyclin
      D1 was downregulated in various cancer cell lines under hypoxic conditions, which
      was independent of p21 and HIF-1 and -2alpha expression. It was also found that
      cyclin D1 was destabilized by the ubiquitin-proteasome system and this
      degradation process was highly activated by hypoxia. Moreover, antioxidants
      prevented the hypoxic degradation of cyclin D1 and hydrogen peroxide destabilized
      cyclin D1 in normoxia. Finally, we demonstrated that ectopic expression of cyclin
      D1 rescued hypoxic growth arrest in both p21+/+ and p21-/- HCT116 cells. Given
      the results, we here propose that reactive oxygen species-mediated cyclin D1
      degradation contributes to tumor growth retardation in hypoxic environments.

PMID- 18616528
TI  - Phosphatidylinositol 3-kinase inhibitors: promising drug candidates for cancer
      therapy.
AB  - Phosphatidylinositol 3-kinases (PI3K) are a group of lipid kinases that
      phosphorylate phosphoinositides at the 3-hydroxyl group of the inositol ring to
      generate phosphatidylinositol 3,4,5-trisphosphate, a second messenger with key
      roles in fundamental cellular responses such as cell proliferation and
      metabolism. Frequent mutations found in or amplification of the PIK3CA gene and
      loss of phosphatase and tensin homolog deleted on chromosome 10 function in human
      tumors suggest that PI3K is a potential target for cancer therapy. During the
      last 5 years, several specific PI3K inhibitors were developed that were directed
      against various diseases. Some of them revealed potent anticancer efficacy and
      are now undergoing clinical trials. Some PI3K inhibitors showed antiangiogenic
      effects. Combined use of PI3K inhibitors with other chemotherapeutic agents or
      with radiotherapy produced synergistic therapeutic efficacies in treating cancer
      and showed reduced side effects. The rapid progress made in developing novel PI3K
      inhibitors in recent years promises bright prospects for finding a PI3K-targeted
      anticancer drug in the near future.

PMID- 18616529
TI  - Autophagy is activated in pancreatic cancer cells and correlates with poor
      patient outcome.
AB  - Because autonomous proliferating cancer cells are often exposed to hypoxic
      conditions, there must be an alternative metabolic pathway, such as autophagy,
      that allows them to obtain energy when both oxygen and glucose are depleted. We
      previously reported finding that autophagy actually contributes to cancer cell
      survival in colorectal cancers both in vitro and in vivo. Pancreatic cancer
      remains a devastating and poorly understood malignancy, and hypoxia in pancreatic
      cancers is known to increase their malignant potential. In the present study
      archival pancreatic cancer tissue was retrieved from 71 cases treated by curative
      pancreaticoduodenectomy. Autophagy was evaluated by immunohistochemical staining
      with anti-LC3 antibody, as LC3 is a key component of autophagy and has been used
      as a marker of autophagy. The results showed that strong LC3 expression in the
      peripheral area of pancreatic cancer tissue was correlated with a poor outcome (P
      = 0.0170) and short disease-free period (P = 0.0118). Two of the most significant
      correlations among the clinicopathological factors tested were found between the
      peripheral intensity level of LC3 expression and tumor size (P = 0.0098) or tumor
      necrosis (P = 0.0127). Activated autophagy is associated with pancreatic cancer
      cells, and autophagy is thought to be a response to factors in the cancer
      microenvironment, such as hypoxia and poor nutrient supply. This is the first
      study to report the clinicopathological significance of autophagy in pancreatic
      cancer.

PMID- 18616530
TI  - Mutation analysis of TMC1 identifies four new mutations and suggests an
      additional deafness gene at loci DFNA36 and DFNB7/11.
AB  - Hearing loss is the most frequent sensorineural disorder affecting 1 in 1000
      newborns. In more than half of these babies, the hearing loss is inherited.
      Hereditary hearing loss is a very heterogeneous trait with about 100 gene
      localizations and 44 gene identifications for non-syndromic hearing loss.
      Transmembrane channel-like gene 1 (TMC1) has been identified as the disease
      causing gene for autosomal dominant and autosomal recessive non-syndromic hearing
      loss at the DFNA36 and DFNB7/11 loci, respectively. To date, 2 dominant and 18
      recessive TMC1 mutations have been reported as the cause of hearing loss in 34
      families. In this report, we describe linkage to DFNA36 and DFNB7/11 in 1 family
      with dominant and 10 families with recessive non-syndromic sensorineural hearing
      loss. In addition, mutation analysis of TMC1 was performed in 51 familial Turkish
      patients with autosomal recessive hearing loss. TMC1 mutations were identified in
      seven of the families segregating recessive hearing loss. The pathogenic variants
      we found included two known mutations, c.100C>T and c.1165C>T, and four new
      mutations, c.2350C>T, c.776+1G>A, c.767delT and c.1166G>A. The absence of TMC1
      mutations in the remaining six linked families implies the presence of mutations
      outside the coding region of this gene or alternatively at least one additional
      deafness-causing gene in this region. The analysis of copy number variations in
      TMC1 as well as DNA sequencing of 15 additional candidate genes did not reveal
      any proven pathogenic changes, leaving both hypotheses open.

PMID- 18616531
TI  - MLPA and cDNA analysis improves COL4A5 mutation detection in X-linked Alport
      syndrome.
AB  - The X-linked form of Alport syndrome (AS) is caused by mutations in the COL4A5
      gene encoding the alpha5 chain of type IV collagen. Most COL4A5 mutations are
      individual, and mutation analysis is complicated by the size of the gene and the
      number of exons. Larger structural rearrangements account for 10-15% of
      mutations. We have established a method for mutation analysis of COL4A5 based on
      reverse transcriptase-polymerase chain reaction analysis of mRNA from cultured
      skin fibroblasts and multiplex ligation-dependent probe amplification (MLPA) on
      genomic DNA. One advantage of using skin biopsies for the mRNA analysis is the
      possibility of immunohistochemical staining for the alpha5(IV) chain on skin
      sections to support a diagnosis of X-linked AS. A mutation was detected in all
      five cases included. One patient presenting with AS and diffuse leiomyomatosis
      was found to have a COL4A5 deletion extending into and comprising COL4A6 exons 1,
      1', and 2. We have evaluated the MLPA assay on samples from 67 previously tested
      AS patients (45 males and 22 females) and 20 controls. We found that the
      combination of cDNA and MLPA analysis improves the mutation detection rate in
      COL4A5 and that MLPA should be the first step in genetic testing for X-linked AS.

PMID- 18616532
TI  - "Gloves-and-socks" melanoma: does histology make a difference?
AB  - BACKGROUND: Acral lentiginous melanoma (ALM) is associated with low survival.
      OBJECTIVE: The aim of the study was to compare the clinical course of ALM, non
      ALM hand and foot melanoma, and melanoma of the extremities in nonacral
      locations. METHODS: Data on 168 patients operated on for cutaneous melanoma of
      the extremities from 1993 to 2005 were examined. Twenty-nine had ALM, 16 non-ALM,
      and 123 other-extremity melanoma. All known melanoma prognosticators were
      analyzed for their impact on survival at a median of 53 months' follow-up.
      RESULTS: The ALM group was significantly older (p=.015). No differences between
      the ALM and non-ALM groups were noted in tumor characteristics, lymph node
      status, and survival. However, the other-extremity melanoma group presented with
      significantly thinner lesions, fewer positive sentinel lymph nodes, and lower
      tumor stage and, consequently, had significantly better disease-specific and
      disease-free survival (p=.006, p=.0001). The acral lesions were nearly free of
      peritumoral lymphocytic infiltration. Multivariate analysis identified only tumor
      thickness (p=.0127), stage (p=.00001), and patient age (p=.012) as independent
      prognosticators of disease-specific survival. CONCLUSION: Cutaneous melanomas in
      acral sites, regardless of histology, tend to be diagnosed at an advanced stage
      probably owing to older patient age, difficult-to-see sites, and biologic
      factors, leading to reduced patient survival.

PMID- 18616533
TI  - Nail unit tumors: a study of 234 patients in the dermatology department of the
      "Dr Manuel Gea Gonzalez" General Hospital in Mexico City.
AB  - BACKGROUND: The frequency of nail unit tumors is not well known because they are
      often misdiagnosed, and the clinical appearance of benign and malignant tumors is
      not characteristic. PATIENTS AND METHODS: A total of 234 patients from the
      dermatology department of a general hospital in Mexico City were included in this
      study, from January 1982 to November 2006. RESULTS: The tumors most frequently
      diagnosed were fibrous tumors (29.05%), osteocartilaginous tumors (21.79%), and
      myxoid pseudocysts (11.96%). Malignant melanoma occupied the fourth place
      (9.82%), and the second most frequent malignant tumor was squamous cell carcinoma
      (SCC; 4.70%). Among other tumors were glomus, neurofibromas, giant cell tumors of
      tendon sheath, and pyogenic granulomas. The nail plate was affected in 46.5% of
      the cases studied. CONCLUSION: This study in a Mexican population sheds light on
      the frequency and the alterations produced by nail unit tumors, which we must
      keep in mind for a more accurate diagnosis.

PMID- 18616534
TI  - Topical 10% zinc sulfate solution for treatment of melasma.
AB  - BACKGROUND: Multiple modalities have been used in the treatment of melasma, such
      as bleaching agents, chemical peels, and antioxidants. Topical zinc sulfate has
      peeling and antioxidant effects. OBJECTIVE: The objective was to evaluate the
      efficacy and safety of topical 10% zinc sulfate solution in the treatment of
      melasma. PATIENTS & METHODS: This study was conducted at the Department of
      Dermatology & Venereology, Baghdad Teaching Hospital. Twenty-eight patients with
      melasma were treated with 10% zinc sulfate solution. Every patient was instructed
      to apply the formula twice daily and to be seen every 2 weeks for 2 months. The
      severity of melasma was assessed before, during, and after treatment with the
      melasma area and severity index (MASI). All patients were instructed to apply a
      broad-spectrum sunscreen with SPF>30 before sun exposure during treatment and for
      the 3-month follow-up period. RESULTS: Fourteen patients were treated with 10%
      zinc sulfate solution. The mean MASI score before treatment was 9.45, which
      changed to 4.70 after therapy. This corresponds to a percentage improvement of
      49.78% and was statistically significant (p<.0005). No side effects were reported
      apart from a mild stinging sensation reported in a few patients. Most patients
      maintained improvement 3 months after cessation of therapy. CONCLUSION: Topical
      10% zinc sulfate solution is a new effective, safe, and noncostly formulation in
      the treatment of melasma.

PMID- 18616535
TI  - Chemical lumbar sympathetic block in the treatment of plantar hyperhidrosis: a
      study of 69 patients.
AB  - BACKGROUND: Plantar hyperhidrosis is a distressing problem that can affect a
      patient's quality of life. Although various conservative modalities have been
      suggested, severe plantar hyperhidrosis is often not sufficiently treated.
      OBJECTIVE: The aim of this study was to evaluate the safety and the effectiveness
      of a chemical lumbar sympathetic block (CLSB) with alcohol in patients with
      severe plantar hyperhidrosis. METHOD: Sixty-nine patients were treated by a
      neurolytic lumbar block. A single-needle or two-needle technique was used with
      patients in the prone position. RESULTS: Of 138 procedures, the number of
      successful blocks was 68 (49.3%) for L3 to L4 and 28 (20.3%) for L4 to L5. The
      degree of anhydrosis was excellent in 6 patients (8.7%), good in 32 patients
      (46.4%), fair in 32 patients (34.8%), and poor in 7 patients (10.1%). Of 69
      patients, 56 (81.1%) were partially or fully satisfied. Noted complications
      included temporary sexual dysfunction in 1 patient, compensatory hyperhidrosis in
      1 patient, and transient genitofemoral neuritis in 3 patients. Although 62
      patients (89.9%) recurred at 6 to 18 months, 3 patients (4.3%) remained stable
      until 18 to 24 months. CONCLUSION: The careful use of CLSB on an outpatient basis
      can be a safe, minimally invasive, and effective treatment for severe plantar
      hyperhidrosis.

PMID- 18616536
TI  - A prospective study of incidence of saphenous nerve injury after total great
      saphenous vein stripping.
AB  - BACKGROUND AND OBJECTIVES: Total stripping of the great saphenous vein (GSV) is a
      validated surgical strategy of treating patients with primary varicose veins
      (PVV). An often cited, but not well documented and studied, complication of total
      stripping is postoperative damage of the saphenous nerve (SN). OBJECTIVE: The
      objective was to evaluate the incidence of SN damage and to assess the
      therapeutic efficacy after total stripping of the GSV. MATERIALS AND METHODS:
      Patients undergoing total stripping of the GSV because of PVV in the entire lower
      limb were enrolled. Pre- and postoperative neurologic examination was performed
      to identify potential sensory neurologic deficits. RESULTS: Total stripping of
      the GSV in 69 limbs occurred because of pain (9%) or a tired feeling in the limbs
      (77%) or for cosmetic reasons (14%). The overall incidence of postoperative
      sensory neurologic deficits was 7 and 6%, respectively, after 6-week follow-up
      and both 3% after 3-month follow-up. In 99% of the patients, total stripping of
      the GSV resulted in reduction of the primary signs and symptoms. CONCLUSION: The
      incidence of SN damage after total stripping of the GSV is low. Thus, total
      stripping of the GSV resulted in improvement of the primary complaint in almost
      all patients. Total stripping of the GSV is an effective surgical strategy in
      treating PVV.

PMID- 18616537
TI  - Adipose-derived stem cells and their secretory factors as a promising therapy for
      skin aging.
AB  - BACKGROUND: Adipose-derived stem cells (ADSCs) and their secretory factors can
      stimulate collagen synthesis and migration of fibroblasts during the wound
      healing process. Conventional treatments for skin aging, such as lasers and
      topical regimens, induce new collagen synthesis via activation of dermal
      fibroblasts or growth factors. Considering the results of our previous study,
      ADSCs can also be used for the treatment of skin aging. OBJECTIVE: The aim was to
      verify the effectiveness of ADSCs for the treatment of skin aging. METHODS: We
      analyzed secretory factors of ADSCs and intradermally injected ADSCs (1 x 10(6)
      cells in 1 mL of Hanks' buffered salt solution) and conditioned media of ADSCs on
      the back of a micropig. In addition, as a pilot study, intradermal injections of
      purified autologous processed lipoaspirate (PLA) cells were tried with the
      photoaged skin of one patient. RESULTS: We demonstrated that ADSCs produce many
      useful growth factors, increase collagen production in animal study, and reverse
      skin aging in human trial. CONCLUSION: ADSCs and their secretory factors show
      promise for application in cosmetic dermatology, especially in the treatment of
      skin aging.

PMID- 18616538
TI  - Bleomycin in dermatology: a review of intralesional applications.
AB  - Intralesional bleomycin has been favorably used off-label to treat various skin
      conditions. These include warts, hemangiomas, vascular malformations,
      telangiectasias, several types of cutaneous malignancies, condyloma acuminata,
      and the lesions of leishmaniasis cutis. Currently, there is a limited amount of
      evidence from randomized placebo-controlled trials comparing intralesional
      bleomycin with other local treatments for these disorders. In this article, we
      review the pharmacodynamics, mechanism of action, safety profile, and clinical
      applications of intralesional bleomycin. Dosages, techniques for administration,
      and efficacy of intralesional bleomycin for each aforementioned clinical entity
      are also provided. Given its ease and safety in administration, efficacy, and
      availability, off-label use of intralesional bleomycin can be considered another
      primary and/or adjunctive therapy for various common cutaneous conditions by
      practitioners in dermatology today.

PMID- 18616539
TI  - Letter: creating preoperative images of subungual glomus tumors.

PMID- 18616540
TI  - Letter: pilonidal cyst of the scalp.

PMID- 18616541
TI  - Letter: weighing the anchor flap.

PMID- 18616542
TI  - Munchausen's syndrome: a rare self-mutilation syndrome.

PMID- 18616543
TI  - Bioengineered skin for aesthetic reconstruction of the tip of the nose: a case
      report.

PMID- 18616544
TI  - Nonrandom extinction leads to elevated loss of angiosperm evolutionary history.
AB  - The phylogenetic clustering of extinction may jeopardize the existence of entire
      families and genera, which can result in elevated reductions of evolutionary
      history (EH), trait diversity, and ecosystem functioning. Analyses of globally
      threatened birds and mammals suggest current extinction threats will result in a
      much higher loss of EH than random extinction scenarios, while the analyses of
      the taxonomical distribution of regionally rare plants find the opposite pattern.
      The disproportionately high number of rare plant species within species-rich
      families potentially suggests that lower losses of plant EH will be sustained
      than expected under random extinction. We show that at a global scale, this is
      not the case. Species-poor (especially monotypic) angiosperm families are more
      often at risk of extinction than expected. Because these high-risk species-poor
      families are as evolutionarily distinct as other families, the expected family
      level EH plausibly lost in the next 100 years exceeds that predicted from random
      extinction by up to approximately 1165 million years.

PMID- 18616545
TI  - Why equalising trade-offs aren't always neutral.
AB  - Equalising trade-offs, such as seed mass vs. number, have been invoked to
      reconcile neutral theory with observed differences between species. This is an
      appealing explanation for the dramatic seed size variation seen within guilds of
      otherwise similar plants: under size-symmetric competition, where resource
      capture is proportional to mass, the outcome of competition should be insensitive
      to whether species produce many small seeds or few large ones. However, under
      this assumption, stochastic variation in seed rain leads to exclusion of all but
      the smallest-seeded species. Thus stochasticity in seed arrivals, a process that
      was previously thought to generate drift, instead results in deterministic
      competitive exclusion. A neutral outcome is possible under one special case of a
      more general equalising framework, where seed mass affects survival but not
      competition. Further exploration of the feasibility of neutral trade-offs is
      needed to understand the respective roles of neutrality and niche structure in
      community dynamics.

PMID- 18616546
TI  - Beneficial acclimation and the Bogert effect.
AB  - Few studies have examined the extent to which phenotypic plasticity in a given
      trait might be influenced by behavioural responses to an environmental cue.
      Regulatory behaviour might eliminate environmental variation such that little
      selection for physiological change would take place. Here, to test this Bogert
      effect on acclimation, we use two life-stages of a kelp fly that inhabit the same
      habitat, but differ profoundly in their behaviour. We predicted that when denied
      opportunities for behavioural regulation, mobile, though brachypterous adults
      would show a performance advantage in most thermal environments following
      acclimation to their preferred temperature(s). By contrast, in the less mobile
      larvae, that have a broader thermal preference, beneficial acclimation would be
      more evident. Ordered factor anova with orthogonal polynomial contrasts revealed
      that adults recovered faster from chill coma following any one of six short-term
      temperature treatments if they had been acclimated at low temperature, whilst
      larvae showed beneficial acclimation.

PMID- 18616547
TI  - Challenging urban species diversity: contrasting phylogenetic patterns across
      plant functional groups in Germany.
AB  - Cities are hotspots of plant species richness, harboring more species than their
      rural surroundings, at least over large enough scales. However, species richness
      does not necessarily cover all aspects of biodiversity such as phylogenetic
      relationships. Ignoring these relationships, our understanding of how species
      assemblages develop and change in a changing environment remains incomplete.
      Given the high vascular plant species richness of urbanized areas in Germany, we
      asked whether these also have a higher phylogenetic diversity than rural areas,
      and whether phylogenetic diversity patterns differ systematically between species
      groups characterized by specific functional traits. Calculating the average
      phylogenetic distinctness of the total German flora and accounting for spatial
      autocorrelation, we show that phylogenetic diversity of urban areas does not
      reflect their high species richness. Hence, high urban species richness is mainly
      due to more closely related species that are functionally similar and able to
      deal with urbanization. This diminished phylogenetic information might decrease
      the flora's capacity to respond to environmental changes.

PMID- 18616548
TI  - Temporal dynamics within a contemporary latitudinal diversity gradient.
AB  - Poleward declines in species diversity [latitudinal diversity gradients (LDG)]
      remain among the oldest and most widespread of macroecological patterns. However,
      their contemporary dynamics remain largely unexplored even though changing
      ecological conditions, including global change, may modify LDG and their
      respective ecosystems. Here, we examine temporal variation within a temperate
      Northwest Atlantic LDG using 31 years of annual fisheries-independent surveys and
      explore its dynamics in relation to a dominant climate signal [the wintertime
      North Atlantic Oscillation (NAO)] that varies interannually and alters the
      latitudinal gradient of Northwest Atlantic continental shelf bottom water
      temperatures. We found that the slopes of the annual LDG vary dramatically due to
      changes in geographic distributions of 100+ species, variations that are
      concealed within the cumulative, static LDG. These changes are strongly
      associated with changes in NAO sign and strength. This is the first illustration
      of temporal dynamics in a contemporary LDG and the first demonstration of the
      speed at which local environmental variations can alter an LDG. Our findings
      underscore the need to investigate factors that modify LDG separately from those
      that contribute to their origins.

PMID- 18616549
TI  - Multiple modes in a coral species abundance distribution.
AB  - Species abundance distributions are an important measure of biodiversity and
      community structure. These distributions are affected by sampling, and
      alternative species-abundance models often make similar predictions for small
      sample sizes. Very large samples reveal the relative abundances of rare species,
      and thus provide information about species relative abundances that small samples
      cannot. Here, we present the species-abundance distribution for a sample of >
      40,000 coral colonies at a single site, exceeding existing samples of coral local
      assemblages by over an order of magnitude. This abundance distribution is
      multimodal when examined on a logarithmic scale. Four different model selection
      procedures all indicate that the underlying community abundance distribution has
      at least three modes. We show that the multiple modes are not caused by mixtures
      of species with different habitat preferences. However, spatial aggregation
      partially explains our results. We inspect published work on species abundance
      distributions, and suggest that multimodality may be a common feature of large
      samples.

PMID- 18616550
TI  - Diversity and disease: community structure drives parasite transmission and host
      fitness.
AB  - Changes in host diversity and community structure have been linked to disease,
      but the mechanisms underlying such relationships and their applicability to non
      vector-borne disease systems remain conjectural. Here we experimentally
      investigated how changes in host community structure affected the transmission
      and pathology of the multi-host parasite Ribeiroia ondatrae, which is a
      widespread cause of amphibian limb deformities. We exposed larval amphibians to
      parasites in monospecific or heterospecific communities, and varied host number
      to differentiate between density- and diversity-mediated effects on transmission.
      In monospecific communities, exposure to Ribeiroia significantly increased
      mortality (15%), malformations (40%) and time-to-metamorphosis in toads. However,
      the presence of tree frogs significantly reduced infection in toads, leading to
      fewer malformations and higher survival than observed in monospecific
      communities, providing evidence of parasite-mediated facilitation. Our results
      suggest that interspecific variation in parasite resistance can inhibit parasite
      transmission in multi-species communities, reducing infection and pathology in
      sensitive hosts.

PMID- 18616551
TI  - Increased susceptibility of white spot syndrome virus-infected Litopenaeus
      vannamei to Vibrio campbellii.
AB  - The concept of polymicrobial disease is well accepted in human and veterinary
      medicine but has received very little attention in the field of aquaculture. This
      study was conducted to investigate the synergistic effect of white spot syndrome
      virus (WSSV) and Vibrio campbellii on development of disease in specific pathogen
      free (SPF) shrimp Litopenaeus vannamei. The juvenile shrimp were first injected
      with WSSV at a dose of 30 SID(50) shrimp(-1) (SID(50) = shrimp infectious dose
      with 50% endpoint) and 24 h later with 10(6) colony-forming units (cfu) of V.
      campbellii shrimp(-1). Controls receiving just one of the pathogens or negative
      inocula were included. In the treatment with WSSV only, shrimp started to die at
      48-108 h post injection (hpi) and cumulative mortality reached 100% at 268-336
      hpi. In the treatment with only V. campbellii injection (10(6) cfu shrimp(-1)),
      cumulative mortality reached 16.7%. Shrimp in the dual treatment died very
      quickly after V. campbellii injection and 100% cumulative mortality was obtained
      at 72-96 hpi. When WSSV-injected shrimp were given sonicated V. campbellii
      instead of live V. campbellii, no synergistic effect was observed. Density of V.
      campbellii in the haemolymph of co-infected moribund shrimp collected 10 h after
      V. campbellii injection was significantly higher than in shrimp injected with V.
      campbellii only (P < 0.01). However, there was no difference in WSSV replication
      between shrimp inoculated with WSSV only compared with dually inoculated ones.
      This study revealed that prior infection with WSSV enhances the multiplication
      and disease inducing capacity of V. campbellii in shrimp.

PMID- 18616552
TI  - Factors influencing clinical features of absence seizures.
AB  - PURPOSE: The clinical features of absence seizures in idiopathic generalized
      epilepsy have been held to be syndrome-specific. This hypothesis is central to
      many aspects of epilepsy research yet has not been critically assessed. We
      examined whether specific factors such as epilepsy syndrome, age, and state
      determine the features of absence seizures. METHODS: Children with newly
      presenting absence seizures were studied using video electroencephalography (EEG)
      recording. We analyzed whether a child's epilepsy syndrome, age, state of
      arousal, and provocation influenced specific clinical features of their absence
      seizures: duration, eyelid movements, eye opening, and level of awareness during
      the seizure. RESULTS: Seizures (509) were evaluated in 70 children with the
      following syndromes: Childhood absence epilepsy (CAE), 37; CAE plus
      photoparoxysmal response (PPR), 10; juvenile absence epilepsy (JAE), 8; juvenile
      myoclonic epilepsy (JME), 6; unclassified, 9. Seizure duration was associated
      with epilepsy syndrome as children with JME had shorter seizures than in other
      syndromes, independent of age. Age independently influences level of awareness
      and eye opening. Arousal or provocation affected all features except level of
      awareness. Specific factors unique to the child independently influenced all
      features; the nature of these factors has not been identified. DISCUSSION: The
      view that the clinical features of absence seizures have syndrome-specific
      patterns is not supported by critical analysis. We show that confounding
      variables profoundly affect clinical features and that syndromes also show marked
      variation. Variation in clinical features of absence seizures results from a
      complex interaction of many factors that are likely to be genetically and
      environmentally determined.

PMID- 18616554
TI  - Case-control analysis of ambulance, emergency room, or inpatient hospital events
      for epilepsy and antiepileptic drug formulation changes.
AB  - PURPOSE: Although antiepileptic drugs (AEDs) with multisource generic
      alternatives are becoming more prevalent, no case-control studies have been
      published examining multisource medication use and epilepsy-related outcomes.
      This study evaluated the association between inpatient/emergency epilepsy care
      and the occurrence of a recent switch in AED formulation. METHODS: A case-control
      analysis was conducted utilizing the Ingenix LabRx Database. Eligible patients
      were 12-64 years of age, received >or=145 days of AEDs in the preindex period,
      had continuous eligibility for 6 months preindex, and no prior
      inpatient/emergency care. Cases received care between 7/1/2006 and 12/31/2006 in
      an ambulance, emergency room, or inpatient hospital with a primary epilepsy
      diagnosis. Controls had a primary epilepsy diagnosis in a physician's office
      during the same period. The index date was the earliest occurrence of care in
      each respective setting. Cases and controls were matched 1:3 by epilepsy
      diagnosis and age. Odds of a switch between "A-rated" AEDs within 6 months prior
      to index were calculated. RESULTS: Cases (n = 416) had 81% greater odds of having
      had an A-rated AED formulation switch [odds ratio (OR) = 1.81; 95% confidence
      interval (CI) = 1.25 to 2.63] relative to controls (n = 1248). There were no
      significant differences between groups regarding demographics or diagnosis.
      Significant differences were found with regard to medical coverage type (case
      Medicaid = 4.6%, control Medicaid = 1.8%, p = 0.002). Post hoc analysis results
      excluding Medicaid recipients remained significant and concordant with the
      original analysis. DISCUSSION: This analysis found an association between
      patients receiving epilepsy care in an emergency or inpatient setting and the
      recent occurrence of AED formulation switching involving A-rated generics.

PMID- 18616555
TI  - Idiopathic epilepsy with generalized tonic-clonic seizures only versus idiopathic
      epilepsy with phantom absences and generalized tonic-clonic seizures: one or two
      syndromes?
AB  - PURPOSE: To define the relationship between two syndromes of idiopathic
      generalized epilepsy (IGE) with apparently similar phenotypes: The form with
      generalized tonic-clonic seizures only (IGE-GTCS) and that with phantom absences
      (IGE-PA). METHODS: We compared the electroclinical features of 33 consecutive
      patients with GTCS and generalized spike wave (GSW); 18 had only GTCS and were
      diagnosed as IGE-GTCS, and 15 had hitherto unnoticed mild absences on the
      electroencephalography (EEG) and were diagnosed as IGE-PA. All patients were
      subjected to the same diagnostic workout, including video EEG during
      hyperventilation with breath counting (HBC). Patients with a clinical history of
      absences or myoclonic seizures were excluded. RESULTS: PA were easily identified
      with the first or second EEG in 14 of 15 patients with IGE-PA and always with
      sleep-deprived EEGs; conversely, PA did not occur in the IGE-GTCS patients
      despite using more EEGs. GTCS were twice as frequent in the IGE-GTCS group and
      tended to occur on awakening, whereas episodes of absence status affected twice
      as many patients with IGE-PA. The hereditary risk was 30% in the IGE-GTCS and
      6.7% in IGE-PA. GSW had a strong polyspike component in IGE-PA and were briefer
      in IGE-GTCS. There is no evidence for a maturational influence on the duration of
      GSW in either syndrome. CONCLUSION: Our findings clearly indicate that IGE-GTCS
      and IGE-PA are two distinct IGE syndromes and emphasize the role of PA for
      patients' diagnosis and management and for syndromic classification. They also
      appear to validate HBC as a simple, sensitive, and pragmatic method for the
      clinical identification of typical absences.

PMID- 18616553
TI  - Focal generation of paroxysmal fast runs during electrographic seizures.
AB  - PURPOSE: A cortically generated Lennox-Gastaut type seizure is associated with
      spike-wave/poly-spike-wave discharges at 1.0-2.5 Hz and fast runs at 7-16 Hz.
      Here we studied the patterns of synchronization during runs of paroxysmal fast
      spikes. METHODS: Electrographic activities were recorded using multisite
      intracellular and field potential recordings in vivo from cats anesthetized with
      ketamine-xylazine. In different experiments, the recording electrodes were
      located either at short distances (<1 mm) or at longer distances (up to 12 mm).
      The main experimental findings were tested in computational models. RESULTS: In
      the majority of cases, the onset and the offset of fast runs occurred almost
      simultaneously in different recording sites. The amplitude and duration of fast
      runs could vary by orders of magnitude. Within the fast runs, the patterns of
      synchronization recorded in different electrodes were as following: (1)
      synchronous, in phase, (2) synchronous, with phase shift, (3) patchy, repeated in
      phase/phase shift transitions, and (4) nonsynchronous, slightly different
      frequencies in different recording sites or absence of oscillatory activity in
      one of the recording sites; the synchronous patterns (in phase or with phase
      shifts) were most common. All these patterns could be recorded in the same pair
      of electrodes during different seizures, and they were reproduced in a
      computational network model. Intrinsically bursting (IB) neurons fired more
      spikes per cycle than any other neurons suggesting their leading role in the fast
      run generation. CONCLUSIONS: Once started, the fast runs are generated locally
      with variable correlations between neighboring cortical foci.

PMID- 18616556
TI  - Electroclinical features of epilepsy in patients with juvenile type dentatorubral
      pallidoluysian atrophy.
AB  - PURPOSE: To clarify the electroclinical characteristics of epileptic seizures in
      patients with juvenile type dentatorubral-pallidoluysian atrophy (DRPLA).
      METHODS: Seventeen patients with juvenile type DRPLA confirmed by genetic
      analysis were studied retrospectively. The clinical records of all 17 patients
      and the ictal video electroencephalography (EEG) recordings from 12 of the 17
      patients were reviewed. RESULTS: Electroclinical studies in 12 patients
      identified 11 habitual seizures in 6 patients as partial seizures on ictal video
      EEG recordings. Clinical manifestations composed mainly of versions of the head
      and loss of consciousness. These partial seizures were persistently recorded
      throughout the clinical course. Brief generalized seizures (atypical absence and
      myoclonic seizure) were observed in 6 of 12 patients at the early stage. In
      contrast, generalized tonic-clonic seizures (GTCS) were recorded in four advanced
      stage patients who were almost bedridden. Semiological studies in 17 patients
      showed that the prevalence of partial seizures was significantly higher in
      patients with younger epilepsy onset (below 10 years of age; chi(2) test, p <
      0.05) and that the age of epilepsy onset was significantly lower in patients with
      partial seizures than in those without partial seizures (Mann-Whitney U test, p =
      0.02). However, the number of CAG repeats and age at clinical onset were not
      significantly different between two groups. DISCUSSION: Partial seizure is one of
      the common epileptic features in juvenile type DRPLA, especially in patients with
      younger epilepsy onset. Seizure types may be affected in an age-dependent manner
      and change evolutionally during progression of the clinical stage.

PMID- 18616557
TI  - In utero exposure to vigabatrin: no indication of visual field loss.
AB  - The purpose of the study was to determine whether in utero exposure to vigabatrin
      caused visual field loss. Three mothers with four children who had been exposed
      to vigabatrin in utero and who were subsequently formula fed were identified. All
      seven individuals underwent perimetry and imaging of the retinal nerve fiber
      layer (RNFL). All individuals yielded reliable outcomes to perimetry and RNFL
      images of acceptable quality. Two of the three mothers exhibited vigabatrin
      attributed visual field loss and an abnormally attenuated RNFL. The third
      exhibited an upper left quadrantanopia, consistent with previous temporal lobe
      surgery, and a normal RNFL. All four children yielded normal visual fields and
      RNFL thicknesses. The presence of the normal findings for the children is
      reassuring and, if representative, suggests a lack of vigabatrin visual toxicity
      and therefore obviates the need for ophthalmological examination of those exposed
      to vigabatrin prenatally.

PMID- 18616558
TI  - Prolonged infusion of inhibitors of calcineurin or L-type calcium channels does
      not block mossy fiber sprouting in a model of temporal lobe epilepsy.
AB  - PURPOSE: It would be useful to selectively block granule cell axon (mossy fiber)
      sprouting to test its functional role in temporal lobe epileptogenesis. Targeting
      axonal growth cones may be an effective strategy to block mossy fiber sprouting.
      L-type calcium channels and calcineurin, a calcium-activated phosphatase, are
      critical for normal growth cone function. Previous studies have provided
      encouraging evidence that blocking L-type calcium channels or inhibiting
      calcineurin during epileptogenic treatments suppresses mossy fiber sprouting.
      METHODS: Rats were treated systemically with pilocarpine to induce status
      epilepticus, which lasted at least 2 h. Then, osmotic pumps and cannulae were
      implanted to infuse calcineurin inhibitors (FK506 or cyclosporin A) or an L-type
      calcium channel blocker (nicardipine) into the dorsal dentate gyrus. After 28
      days of continuous infusion, extent of mossy fiber sprouting was evaluated with
      Timm staining and stereological methods. RESULTS: Percentages of volumes of the
      granule cell layer plus molecular layer that were Timm-positive were similar in
      infused and noninfused hippocampi. CONCLUSIONS: These findings suggest inhibiting
      calcineurin or L-type calcium channels does not block mossy fiber sprouting in
      the pilocarpine-treated rat model of temporal lobe epilepsy.

PMID- 18616559
TI  - Mechanisms and consequences of bladder cell invasion by uropathogenic Escherichia
      coli.
AB  - Strains of uropathogenic Escherichia coli (UPEC) are the major cause of urinary
      tract infections worldwide. Multiple studies over the past decade have called
      into question the dogmatic view that UPEC strains act as strictly extracellular
      pathogens. Rather, bacterial expression of filamentous adhesive organelles known
      as type 1 pili and Afa/Dr fibrils enable UPEC to invade host epithelial cells
      within the urinary tract. Entry into bladder epithelial cells provides UPEC with
      a protected niche where the bacteria can persist quiescently for long periods,
      unperturbed by host defences and protected from many antibiotic treatments.
      Alternately, internalized UPEC can rapidly multiply, forming large intracellular
      inclusions that can contain several thousand bacteria. Initial work aimed at
      defining the host and bacterial factors that modulate the entry, intracellular
      trafficking, and eventual resurgence of UPEC suggests a high degree of host
      pathogen crosstalk. Targeted disruption of these processes may provide a novel
      means to prevent and treat recurrent, relapsing and chronic infections within the
      urinary tract.

PMID- 18616560
TI  - Near-nerve needle sensory and medial plantar nerve conduction studies in patients
      with small-fiber sensory neuropathy.
AB  - BACKGROUND AND PURPOSE: The aim of this prospective study was to show and compare
      the rate of large-fiber involvement with near-nerve needle sensory (NNNS) nerve
      conduction study (NCS) and with medial plantar NCS recorded with surface
      electrodes in a group of patients who had clinically pure small-fiber sensory
      neuropathy (SFSN) with reduced intra-epidermal nerve fiber density in skin biopsy
      and with normal routine NCS. METHODS AND RESULTS: The study included 19 patients
      with clinically pure SFSN with normal routine NCS results and 17 healthy
      volunteers. Routine NCS, skin biopsy, medial plantar NCS and NNNS NCS were
      performed. NNNS NCS data were evaluated both by using univariate analysis methods
      and by using a multivariate analysis method, principal components analysis (PCA).
      Eight patients (42%) had abnormal results for medial plantar NCS with surface
      electrodes. Seven patients (37%) had abnormal results for NNNS NCS with PCA,
      whilst only four patients with univariate analysis. We found a significant
      correlation between intra-epidermal nerve fiber densities, medial plantar NCS and
      PCA results of NNNS NCS. CONCLUSIONS: This study showed that large-nerve fibers
      are also involved in some patients with pure SFSN and medial plantar NCS can
      accurately diagnose neuropathy without a need for NNNS NCS in patients with
      normal routine NCS.

PMID- 18616561
TI  - Pathway-dependent modulation by P2-purinoceptors in the mouse retina.
AB  - Adenosine trisphosphate (ATP) activates purinoceptors and acts as a
      neurotransmitter in the nervous system. In the retina, we previously reported
      that the immunohistochemical distribution of the subset of P2-purinoceptors
      differs between the ON and OFF pathways. Here, we investigated whether ATP
      activates P2-purinoceptors and modulates the physiological function of the mouse
      retina. We also examined if signal processing by P2-purinoceptors is pathway
      specific. Results showed that ATP activated both ON- and OFF-cholinergic amacrine
      cells. However, responses in OFF-cholinergic amacrine cells were greater than
      those in ON-cholinergic amacrine cells. Pharmacological studies in OFF
      cholinergic amacrine cells showed that the response of OFF-cholinergic amacrine
      cells is mediated P2X(2)-purinoceptors. Further, ATP increased gamma-aminobutyric
      acid (GABA)ergic inhibitory postsynaptic currents (IPSCs) in OFF- but not ON
      cholinergic amacrine cells. The increase in GABAergic IPSCs was mediated by P2
      purinoceptors. P2-purinoceptor-mediated signals suppressed OFF ganglion cells but
      activated ON ganglion cells. Our findings indicate that ATP physiologically
      modulates signal processing of the ON and OFF pathways in a pathway-specific
      manner through P2-purinoceptors.

PMID- 18616562
TI  - Multiple functions of GABA A and GABA B receptors during pattern processing in
      the zebrafish olfactory bulb.
AB  - gamma-Aminobutyric acid (GABA)ergic synapses are thought to play pivotal roles in
      the processing of activity patterns in the olfactory bulb (OB), but their
      functions have been difficult to study during odor responses in the intact
      system. We pharmacologically manipulated GABA(A) and GABA(B) receptors in the OB
      of zebrafish and analysed the effects on odor responses of the output neurons,
      the mitral cells (MCs), by electrophysiological recordings and temporally
      deconvolved two-photon Ca2+ imaging. The blockade of GABA(B) receptors enhanced
      presynaptic Ca2+ influx into afferent axon terminals, and changed the amplitude
      and time course of a subset of MC responses, indicating that GABA(B) receptors
      have a modulatory influence on OB output activity. The blockade of GABA(A)
      receptors induced epileptiform firing, enhanced excitatory responses and
      abolished fast oscillations in the local field potential. Moreover, the
      topological reorganization and decorrelation of MC activity patterns during the
      initial phase of the response was perturbed. These results indicate that GABA(A)
      receptor-containing circuits participate in the balance of excitation and
      inhibition, the regulation of total OB output activity, the synchronization of
      odor-dependent neuronal ensembles, and the reorganization of odor-encoding
      activity patterns. GABA(A) and GABA(B) receptors are therefore differentially
      involved in multiple functions of neuronal circuits in the OB.

PMID- 18616563
TI  - The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory
      related activity of hypoglossal motoneurons in the adult rat.
AB  - Motoneurons integrate interneuronal activity into commands for skeletal muscle
      contraction and relaxation to perform motor actions. Hypoglossal motoneurons
      (HMNs) are involved in essential motor functions such as breathing, mastication,
      swallowing and phonation. We have investigated the role of the gaseous molecule
      nitric oxide (NO) in the regulation of the inspiratory-related activity of HMNs
      in order to further understand how neural activity is transformed into motor
      activity. In adult rats, we observed nitrergic fibers and bouton-like structures
      in close proximity to motoneurons, which normally lack the molecular machinery to
      synthesize NO. In addition, immunohistochemistry studies demonstrated that
      perfusion of animals with a NO donor resulted in an increase in the levels of
      cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble
      guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP
      pathway were micro-iontophoretically applied while performing single-unit
      extracellular recordings in the adult decerebrated rat. Application of a NO
      synthase inhibitor or a sGC inhibitor induced a statistically significant
      reduction in the inspiratory-related activity of HMNs. However, excitatory
      effects were observed by ejection of a NO donor or a cell-permeable analogue of
      cGMP. In slice preparations, application to the bath of a NO donor evoked
      membrane depolarization and a decrease in rheobase, which were prevented by co
      addition to the bath of a sGC inhibitor. These effects were not prevented by
      reduction of the spontaneous synaptic activity. We conclude that NO from afferent
      fibers anterogradely modulates the inspiratory-related activity of HMNs by a cGMP
      dependent mechanism in physiological conditions.

PMID- 18616565
TI  - Behavioural profile of a new mouse model for NPY deficiency.
AB  - The abundantly expressed neuropeptide Y (NPY) plays an important role in anxiety
      and stress reactivity, as exogenous NPY administration reduces anxiety-like
      behaviour in rodents. However, unlike the potent effects of NPY seen in
      pharmacological studies, two independent examinations of a genetic mouse model
      for NPY deficiency have shown only subtle, inconsistent and task-dependent
      anxiety-related phenotypes for male mutants. Here we present results of a newly
      developed germline NPY-knockout model, which has been characterized behaviourally
      using a comprehensive multi-tiered phenotyping strategy. Mice of both sexes were
      investigated in locomotion and exploration tasks, anxiety-related paradigms, a
      hippocampus-dependent memory test and a battery of basic tasks screening for
      sensory and motor functions. Male and female NPY-deficient mice consistently
      demonstrated suppressed levels of locomotion and exploration. Furthermore, mutant
      mice exhibited a pronounced anxiogenic-like phenotype when tested in
      spatiotemporal anxiety-relevant paradigms (i.e. elevated-plus maze, open field
      and light-dark task). Importantly, this phenotype was more pronounced in male NPY
      mutants, revealing a moderate sexually dimorphic impact of NPY deficiency on
      behaviour. Interestingly, lack of NPY did not result in impaired learning and
      memory in either sex. Our carefully selected comprehensive behavioural
      phenotyping strategy revealed a consistent hypolocomotive and sex-dependent
      anxious-like phenotype. This new NPY-knockout mouse model reveals the importance
      of sex-specific testing. It also offers a potent new model for research into
      anxiety-related disorders and suggests potential treatment options for these
      conditions via the NPY system.

PMID- 18616566
TI  - Spatial and temporal sensitivity degradation of primary visual cortical cells in
      senescent rhesus monkeys.
AB  - Human visual function declines with age. Much of this decline is mediated by
      changes in the central visual pathways. In this study we compared the spatial and
      temporal sensitivities of striate cortical cells in young and old paralysed
      macaque monkeys. Extracellular single-unit recordings were employed. Our results
      show that cortical neurons in old monkeys exhibit lower optimal spatial and
      temporal frequencies, lower spatial resolution and lower high temporal frequency
      cut-offs than do cells in young adult monkeys. These changes in old monkeys are
      accompanied by increased visually evoked responses, increased spontaneous
      activities and decreased signal-to-noise ratios. The increased excitability of
      cells in old animals is consistent with an age-related degeneration of
      intracortical inhibition. The degradation of spatial and temporal function in old
      striate cortex should contribute to the decline in visual function that
      accompanies normal aging.

PMID- 18616567
TI  - Bayesian estimation of speciation and extinction probabilities from (in)complete
      phylogenies.
AB  - Speciation and extinction probabilities can be estimated from molecular
      phylogenies of extant species that are complete at the species level. Because
      only a fraction of published phylogenies is complete at the species level,
      methods have been developed to estimate speciation and extinction probabilities
      also from incomplete phylogenies. However, due to different estimation
      techniques, estimates from complete and incomplete phylogenies are difficult to
      compare statistically. Here I show with some examples how existing likelihood
      functions can be used to obtain Bayesian estimates of speciation and extinction
      probabilities, and how this approach is applied to both complete and incomplete
      phylogenies.

PMID- 18616564
TI  - GDNF hyperalgesia is mediated by PLCgamma, MAPK/ERK, PI3K, CDK5 and Src family
      kinase signaling and dependent on the IB4-binding protein versican.
AB  - The function of the isolectin B4 (IB4+)-binding and GDNF-dependent Ret (Ret+)
      expressing non-peptidergic subpopulation of nociceptors remain poorly understood.
      We demonstrate that acute administration of GDNF sensitizes nociceptors and
      produces mechanical hyperalgesia in the rat. Intrathecal IB4-saporin, a selective
      toxin for IB4+/Ret+-nociceptors, attenuates GDNF but not NGF hyperalgesia.
      Conversely, intrathecal antisense to Trk A attenuated NGF but not GDNF
      hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides
      targeting mRNA for versican, the molecule that renders the Ret-expressing
      nociceptors IB4-positive (+), also attenuated GDNF but not NGF hyperalgesia, as
      did ADAMTS-4, a matrix metalloprotease known to degrade versican. Finally,
      inhibitors for all five signaling pathways known to be activated by GDNF at
      GFRa1/Ret: PLCc, CDK5, PI3K,MAPK/ERK and Src family kinases, attenuated GDNF
      hyperalgesia. Our results demonstrate a role of the non-peptidergic nociceptors
      in pain produced by the neurotrophin GDNF and suggest that the IB4-binding
      protein versican functions in the expression of this phenotype.

PMID- 18616568
TI  - Female preferences for aposematic signal components in a polymorphic poison frog.
AB  - Aposematic signals may be subject to conflicting selective pressures from
      predators and conspecifics. We studied female preferences for different
      components of aposematic coloration in the polymorphic poison frog Oophaga
      pumilio across several phenotypically distinct populations. This frog shows
      striking diversity in color and pattern between geographically isolated
      populations in western Panama. Results indicate that male dorsal color is the
      most important determiner of female preferences. We did not find consistent
      evidence for effects of other signal components, such as spotting pattern or
      ventral color. Females in two populations showed assortative preferences mediated
      by male dorsal coloration. In a third population we found incomplete color
      assortative preference behavior, with females exhibiting strong discrimination
      toward one novel color but not another. These results hint at a possible
      interaction between sexual and natural selection: female tolerance of unfamiliar
      coloration patterns could facilitate the establishment of novel phenotypes that
      are favored by other selective pressures (e.g., predator biases). Furthermore,
      our study suggests that specific components of the aposematic signal (i.e.,
      dorsal color, ventral color, and spotting pattern) are affected differently by
      natural and sexual selection.

PMID- 18616569
TI  - Effect of mutation on genetic differentiation among nonequilibrium populations.
AB  - The usefulness of GST and similar measures of genetic differentiation has been
      questioned repeatedly because of their dependence on the amount of heterozygosity
      within populations, creating problems when comparing degrees of divergence at
      loci with different mutation rates. Although the effect of mutation on GST is
      expected to be small in the early phases of divergence, it is unclear for how
      long after separation from a common ancestral population that GST is largely
      unaffected by mutation and by the resulting effect on heterozygosity. We address
      this question through analysis of the recursion equations for gene identity under
      the infinite allele model of mutation, and derive conditions describing when the
      effect of mutation on GST can be ignored under mutation-migration-drift
      equilibrium conditions and during the preceding transition phase. An important
      result is that during the transition phase GST is not only affected by mutation,
      but also by the heterozygosity in the base population from which the
      subpopulations diverged. The effect of mutation on GST is significant from the
      very start of the divergence process when initial heterozygosity is low, whereas
      GST is only weakly affected by mutation in the early phases of differentiation
      when initial heterozygosity is high. Thus, differentiation following a severe
      bottleneck is strongly dependent on mutation. The standardized measure of
      differentiation, G'ST, suggested by Hedrick (2005), may be helpful when comparing
      amounts of divergence at loci with different mutation rates under steady-state
      conditions, provided that migration is very low. In many other situations the use
      of G'ST might be misleading, however, and its application should be exercised
      with caution.

PMID- 18616570
TI  - Age-specific genetic and maternal effects in fecundity of preindustrial Finnish
      women.
AB  - A population's potential for evolutionary change depends on the amount of genetic
      variability expressed in traits under selection. Studies attempting to measure
      this variability typically do so over the life span of individuals, but theory
      suggests that the amount of additive genetic variance can change during the
      course of individuals' lives. Here we use pedigree data from historical Finns and
      a quantitative genetic framework to investigate how female fecundity, throughout
      an individual's reproductive life, is influenced by "maternal" versus additive
      genetic effects. We show that although maternal effects explain variation in
      female fecundity early in life, these effects wane with female age. Moreover,
      this decline in maternal effects is associated with a concomitant increase in
      additive genetic variance with age. Our results thus highlight that single over
      lifetime estimates of trait heritability may give a misleading view of a trait's
      potential to respond to changing selection pressures.

PMID- 18616571
TI  - "Hidden" reproductive conflict between mates in a wild bird population.
AB  - Environmental conditions experienced by a female prior to reproducing may be
      influenced by her mate. Part of such an indirect effect of a male on his
      partner's reproduction may be genetic (indirect genetic effect). However, a
      female's direct and a male's indirect genetic effects need not align. We analyzed
      10,652 records of seasonal timing of laying, an important reproductive trait in
      many organisms, of 1864 male and 1916 female common gulls Larus canus collected
      during 37 years. We show that there is both a direct (female) and an indirect
      (male) genetic effect (explaining 14.5% and 4.8% of the REML estimated variance
      in laying date, respectively), but these are significantly negatively correlated
      (-0.53+/-0.22 SE), indicating that genes for early laying in females are
      associated with genes for a delaying male effect on his partner's laying date
      (and vice versa). There is strong selection for laying early in this population,
      and these sexually antagonistic genetic effects may contribute in maintaining the
      variation in laying date. Our findings provide an empirical demonstration of a
      hitherto largely unstudied level of conflict between mates, with important
      ramifications for our understanding of evolutionary dynamics and mate choice in
      nature.

PMID- 18616573
TI  - Estimating nonlinear selection gradients using quadratic regression coefficients:
      double or nothing?
AB  - The use of regression analysis has been instrumental in allowing evolutionary
      biologists to estimate the strength and mode of natural selection. Although
      directional and correlational selection gradients are equal to their
      corresponding regression coefficients, quadratic regression coefficients must be
      doubled to estimate stabilizing/disruptive selection gradients. Based on a sample
      of 33 papers published in Evolution between 2002 and 2007, at least 78% of papers
      have not doubled quadratic regression coefficients, leading to an appreciable
      underestimate of the strength of stabilizing and disruptive selection. Proper
      treatment of quadratic regression coefficients is necessary for estimation of
      fitness surfaces and contour plots, canonical analysis of the gamma matrix, and
      modeling the evolution of populations on an adaptive landscape.

PMID- 18616574
TI  - Rapid antagonistic coevolution between primary and secondary sexual characters in
      horned beetles.
AB  - Different structures may compete during development for a shared and limited pool
      of resources to sustain growth and differentiation. The resulting resource
      allocation trade-offs have the potential to alter both ontogenetic outcomes and
      evolutionary trajectories. However, little is known about the evolutionary causes
      and consequences of resource allocation trade-offs in natural populations. Here,
      we explore the significance of resource allocation trade-offs between primary and
      secondary sexual traits in shaping early morphological divergences between four
      recently separated populations of the horned beetle Onthophagus taurus as well as
      macroevolutionary divergence patterns across 10 Onthophagus species. We show that
      resource allocation trade-offs leave a strong signature in morphological
      divergence patterns both within and between species. Furthermore, our results
      suggest that genital divergence may, under certain circumstances, occur as a
      byproduct of evolutionary changes in secondary sexual traits. Given the
      importance of copulatory organ morphology for reproductive isolation our findings
      begin to raise the possibility that secondary sexual trait evolution may promote
      speciation as a byproduct. We discuss the implications of our results on the
      causes and consequences of resource allocation trade-offs in insects.

PMID- 18616572
TI  - The loci of evolution: how predictable is genetic evolution?
AB  - Is genetic evolution predictable? Evolutionary developmental biologists have
      argued that, at least for morphological traits, the answer is a resounding yes.
      Most mutations causing morphological variation are expected to reside in the cis
      regulatory, rather than the coding, regions of developmental genes. This "cis
      regulatory hypothesis" has recently come under attack. In this review, we first
      describe and critique the arguments that have been proposed in support of the cis
      regulatory hypothesis. We then test the empirical support for the cis-regulatory
      hypothesis with a comprehensive survey of mutations responsible for phenotypic
      evolution in multicellular organisms. Cis-regulatory mutations currently
      represent approximately 22% of 331 identified genetic changes although the number
      of cis-regulatory changes published annually is rapidly increasing. Above the
      species level, cis-regulatory mutations altering morphology are more common than
      coding changes. Also, above the species level cis-regulatory mutations
      predominate for genes not involved in terminal differentiation. These patterns
      imply that the simple question "Do coding or cis-regulatory mutations cause more
      phenotypic evolution?" hides more interesting phenomena. Evolution in different
      kinds of populations and over different durations may result in selection of
      different kinds of mutations. Predicting the genetic basis of evolution requires
      a comprehensive synthesis of molecular developmental biology and population
      genetics.

PMID- 18616575
TI  - Adaptive sympatric speciation of polychromatic "roundfin" sailfin silverside fish
      in Lake Matano (Sulawesi).
AB  - The significance of sympatric speciation is one of the most controversial topics
      in evolutionary biology. Theory suggests that different factors can lead to
      speciation in full geographical contact, including selection and nonrandom
      mating. Strict criteria have been established for assessing sympatric speciation,
      which have been met in only a very few cases. Here, we investigate
      differentiation among sympatric morphospecies and color morphs of "roundfin"
      sailfin silversides (Telmatherinidae), small freshwater fish endemic to ancient
      Lake Matano in Central Sulawesi (Indonesia). Morphospecies are distinct according
      to body shape (geometric morphometrics), population structure (population-level
      amplified fragment length polymorphism [AFLP] markers), ecology, and mating
      behavior (habitat transects, stomach contents). Explorative genome scans based on
      AFLPs indicate that divergent selection affects only 1.3-4.2% of the analyzed
      loci, suggesting an early stage of speciation. Transect data demonstrate strong
      assortative mating and adaptive niche differentiation. However, we find no
      restrictions in gene flow among the conspicuous male color morphs. In summary,
      our data are consistent with a sympatric mode of divergence among three
      morphospecies under conditions effectively ruling out allopatric scenarios.
      Substantial, but incomplete, reproductive isolation suggests an early stage of
      speciation, most likely due to ecological selection pressure.

PMID- 18616576
TI  - Granulomatous rosacea and Crohn's disease in a patient homozygous for the Crohn
      associated NOD2/CARD15 polymorphism R702W.
AB  - NOD2/CARD15 belongs to the N-terminal caspase recruitment domain family of
      proteins involved in regulating NF-kB activation in response to inflammatory
      stimuli transduced through Toll-like receptors. Mutations and polymorphisms in
      the NOD2/CARD15 gene reduce antibacterial responses and are associated with
      granulomatous inflammatory conditions such as Blau syndrome and early-onset
      sarcoidosis. The polymorphism R702W (arginine to tryptophan) is strongly
      associated with susceptibility to Crohn's disease in Caucasian populations. Skin
      abnormalities (other than cutaneous manifestations of Crohn's disease) have not
      been previously associated with R702W. We report on a female patient homozygous
      for R702W who developed granulomatous rosacea at the age of 12 years old. From
      the occurrence in the context of Crohn associated with R702W, we speculate that
      granulomatous rosacea may be an entity distinct from other forms of rosacea,
      which are associated with increased production of antibacterial proteins such as
      cathelicidin.

PMID- 18616577
TI  - Photocarcinogenesis of topical tazarotene and isotretinoin alone and in
      combination with valproic acid in hairless mice.
AB  - Retinoids and the histone deacetylase inhibitor valproic acid have shown
      anticancer properties, but the photocarcinogenic or photoprotective effect is
      unclear. Therefore, we investigated whether a topical formulation of valproic
      acid is photocarcinogenic or photoprotective in hairless female C3.Cg/TifBomTac
      immunocompetent mice exposed to simulated solar radiation (SSR) and whether
      valproic acid changes the effect of the retinoids: tazarotene and isotretinoin.
      The products were applied on the dorsal skin of 400 mice (five times weekly)
      followed by SSR (three times weekly) 3-4 h after the application. This was
      performed during 12 months or until death. Tumors appeared sooner in groups
      treated with tazarotene and isotretinoin compared with that of the group treated
      with valproic acid and the control group. The present study shows that valproic
      acid alone is not photocarcinogenic or photoprotective in hairless mice. When
      valproic acid is combined with tazarotene or isotretinoin, it does not change
      their photocarcinogenicity significantly.

PMID- 18616578
TI  - Biosynthesis of isoprenoids: studies on the mechanism of 2C-methyl-D-erythritol-4
      phosphate synthase.
AB  - 2C-Methyl-D-erythritol-4-phosphate synthase, encoded by the ispC gene (also
      designated dxr), catalyzes the first committed step in the nonmevalonate
      isoprenoid biosynthetic pathway. The reaction involves the isomerization of 1
      deoxy-D-xylulose 5-phosphate, giving a branched-chain aldose derivative that is
      subsequently reduced to 2C-methyl-D-erythritol 4-phosphate. The isomerization
      step has been proposed to proceed as an intramolecular rearrangement or a
      retroaldol-aldol sequence. We report the preparation of (13)C-labeled substrate
      isotopologs that were designed to optimize the detection of an exchange of
      putative cleavage products that might occur in the hypothetical retroaldol-aldol
      reaction sequence. In reaction mixtures containing large amounts of 2C-methyl-D
      erythritol-4-phosphate synthase from Escherichia coli, Mycobacterium tuberculosis
      or Arabidopsis thaliana, and a mixture of [1-(13)C(1)]-2C-methyl-D-erythritol 4
      phosphate and [3-(13)C(1)]2C-methyl-D-erythritol 4-phosphate, the reversible
      reaction could be followed over thousands of reaction cycles. No fragment
      exchange could be detected by NMR spectroscopy, and the frequency of exchange, if
      any, is less than 5 p.p.m. per catalytic cycle. Hydroxyacetone, the putative
      second fragment expected from the retroaldol cleavage, was not incorporated into
      the enzyme product. In contrast to other reports, IspC did not catalyze the
      isomerisation of 1-deoxy-D-xylulose 5-phosphate to give 1-deoxy-L-ribulose 5
      phosphate under any conditions tested. However, we could show that the
      isomerization reaction proceeds at room temperature without a requirement for
      enzyme catalysis. Although a retroaldol-aldol mechanism cannot be ruled out
      conclusively, the data show that a retroldol-aldol reaction sequence would have
      to proceed with very stringent fragment containment that would apply to the
      enzymes from three genetically distant organisms.

PMID- 18616579
TI  - Microcin J25 induces the opening of the mitochondrial transition pore and
      cytochrome c release through superoxide generation.
AB  - Microcin J25, an antimicrobial lasso-structure peptide, induces the opening of
      mitochondrial permeability transition pores and the subsequent loss of cytochrome
      c. The microcin J25 effect is mediated by the stimulation of superoxide anion
      overproduction. An increased uptake of calcium is also involved in this process.
      Additional studies with superoxide dismutase, ascorbic acid and different
      specific inhibitors, such as ruthenium red, cyclosporin A and Mn(2+), allowed us
      to establish a time sequence of events starting with the binding of microcin J25,
      followed by superoxide anion overproduction, opening of mitochondrial
      permeability transition pores, mitochondrial swelling and the concomitant leakage
      of cytochrome c.

PMID- 18616580
TI  - Change of bacterial communities in sediments along Songhua River in Northeastern
      China after a nitrobenzene pollution event.
AB  - More than 100 tons of nitrobenzene and related compounds were released into
      Songhua River due to the explosion of an aniline production factory in November,
      2005. Sediment samples were taken from the heavily polluted drainage canal, one
      upstream and three downstream river sites. The change of bacterial community
      structures along the river was studied by denaturing gradient gel electrophoresis
      (DGGE) and cloning and sequencing of 16S rRNA genes with five clone libraries
      constructed and 101 sequences acquired representing 172 clones. Both DGGE
      profiles and sequences of 16S rRNA genes from clone libraries demonstrated that
      the contaminated drainage canal and three downstream river sites were similar in
      that all had Betaproteobacteria, mainly grouped into Comamonadaceae, as the
      dominant group of bacteria, and all had Firmicutes, primarily as Clostridium spp.
      These results suggest that these latter two groups of bacteria may play potential
      roles in degradation and detoxification of nitrobenzene in the present
      contaminated river environments.

PMID- 18616581
TI  - Patchy distribution of flexible genetic elements in bacterial populations
      mediates robustness to environmental uncertainty.
AB  - The generation and maintenance of genetic variation seems to be a general
      ecological strategy of bacterial populations. Thereby they gain robustness to
      irregular environmental change, which is primarily the result of the dynamic
      evolution of biotic interactions. A benefit of maintaining population
      heterogeneity is that only a fraction of the population has to bear the cost of
      not (yet) beneficial deviation. On evolutionary time frames, an added value of
      the underlying mechanisms is evolvability, i.e. the heritable ability of an
      evolutionary lineage to generate and maintain genetic variants that are
      potentially adaptive in the course of evolution. Horizontal gene transfer is an
      important mechanism that can lead to differences between individuals within
      bacterial populations. Broad host-range plasmids foster this heterogeneity
      because they are typically present in only a fraction of the population and
      provide individual cells with genetic modules newly acquired from other
      populations or species. We postulate that the benefit of robustness on population
      level could balance the cost of transfer and replication functions that plasmids
      impose on their hosts. Consequently, mechanisms that make a subpopulation
      conducive to specific conjugative plasmids may have evolved, which could explain
      the persistence of even cryptic plasmids that do not encode any traits.

PMID- 18616582
TI  - Influence of plant developmental stage on microbial community structure and
      activity in the rhizosphere of three field crops.
AB  - Seasonal shifts in rhizosphere microbial populations were investigated to follow
      the influence of plant developmental stage. A field study of indigenous microbial
      rhizosphere communities was undertaken on pea (Pisum satvium var. quincy), wheat
      (Triticum aestivum var. pena wawa) and sugar beet (Beta vulgaris var. amythyst).
      Rhizosphere community diversity and substrate utilization patterns were followed
      throughout a growing season, by culturing, rRNA gene density gradient gel
      electrophoresis and BIOLOG. Culturable bacterial and fungal rhizosphere community
      densities were stable in pea and wheat rhizospheres, with dynamic shifts observed
      in the sugar beet rhizosphere. Successional shifts in bacterial and fungal
      diversity as plants mature demonstrated that different plants select and define
      their own functional rhizosphere communities. Assessment of metabolic activity
      and resource utilization by bacterial community-level physiological profiling
      demonstrated greater similarities between different plant species rhizosphere
      communities at the same than at different developmental stages. Marked temporal
      shifts in diversity and relative activity were observed in rhizosphere bacterial
      communities with developmental stage for all plant species studied. Shifts in the
      diversity of fungal and bacterial communities were more pronounced in maturing
      pea and sugar beet plants. This detailed study demonstrates that plant species
      select for specialized microbial communities that change in response to plant
      growth and plant inputs.

PMID- 18616583
TI  - Two-dimensional mapping of photopigment distribution and activity of Chloroflexus
      like bacteria in a hypersaline microbial mat.
AB  - Pigment analysis in an intact hypersaline microbial mat by hyperspectral imaging
      revealed very patchy and spatially uncorrelated distributions of photopigments
      Chl a and BChl a/c, which are characteristic photopigments for oxygenic (diatoms
      and cyanobacteria) and anoxygenic phototrophs (Chloroflexaceae). This finding is
      in contrast to the expectation that these biomarker pigments should be spatially
      correlated, as oxygenic phototrophs are thought to supply the Chloroflexaceae
      members with organic substrates for growth. We suggest that the heterogeneous
      occurrence is possibly due to sulfide, whose production by sulfate-reducing
      bacteria may be spatially heterogeneous in the partially oxic photic zone of the
      mat. We furthermore mapped the near-infra-red-light controlled respiration of
      Chloroflexaceae under light and dark conditions and found that Chloroflexaceae
      are responsible for a major part of oxygen consumption at the lower part of the
      oxic zone in the mat. The presence of Chloroflexaceae was further confirmed by
      FISH probe and 16S rRNA gene clone library analysis. We assume that species
      related to the genera Oscillochloris and 'Candidatus Chlorothrix', in contrast to
      those related to Chloroflexus and Roseiflexus, depend less on excreted
      photosynthates but more on the presence of free sulfide, which may explain their
      presence in deeper parts of the mat.

PMID- 18616584
TI  - Spatial heterogeneity in sediment-associated bacterial and eukaryotic communities
      in a landfill leachate-contaminated aquifer.
AB  - Heterogeneity in eukaryotic and bacteria community structure in surface and
      subsurface sediment samples downgradient of the Banisveld landfill (The
      Netherlands) was studied using a culturing-independent molecular approach. Along
      a transect covering the part of the aquifer most polluted by landfill leachate,
      sediment was sampled at 1-m depth intervals, until a depth of 5.5 m, at four
      distances from the landfill. Two drillings were placed in a nearby clean area as
      a reference. Denaturing gradient gel electrophoresis banding patterns revealed
      high bacterial and eukaryotic diversity and complex community structures.
      Bacteria and eukaryotic community profiles in polluted samples grouped different
      from those in clean samples. Bacteria community profiles in surface samples
      clustered together and separately from subsurface community profiles. Subsurface
      bacteria profiles clustered in a location-specific manner. Eukaryotic community
      structure did not significantly relate to distance from the landfill or depth. No
      significant spatial autocorrelation of bacteria or eukaryotic communities was
      observed over 1-m depth intervals per sampling location. Spatial heterogeneity in
      sediment-associated bacterial communities appears to be much larger than in
      groundwater. We discuss how on the one hand, spatial heterogeneity may complicate
      the assessment of microbial community structure and functioning, while on the
      other it may provide better opportunities for natural attenuation.

PMID- 18616585
TI  - Functional robustness and gene pools of a wastewater nitrification reactor:
      comparison of dispersed and intact biofilms when stressed by low oxygen and low
      pH.
AB  - The functional robustness of biofilms in a wastewater nitrification reactor, and
      the gene pools therein, were investigated. Nitrosomonas and Nitrosospira spp.
      were present in similar amounts (cloning-sequencing of ammonia-oxidizing bacteria
      16S rRNA gene), and their estimated abundance (1.1 x 10(9) cells g(-1) carrier
      material, based on amoA gene real-time PCR) was sufficient to explain the
      observed nitrification rates. The biofilm also had a diverse community of
      heterotrophic denitrifying bacteria (cloning-sequencing of nirK). Anammox 16S
      rRNA genes were detected, but not archaeal amoA. Dispersed biofilms (DB) and
      intact biofilms (IB) were incubated in gas-tight reactors at different pH levels
      (4.5 and 5.5 vs. 6.5) while monitoring O(2) depletion and concentrations of NO,
      N(2)O and N(2) in the headspace. Nitrification was severely reduced by suboptimal
      O(2) concentrations (10-100 microM) and low pH (IB was more acid tolerant than
      DB), but the N(2)O/NO(3)(-) product ratio of nitrification remained low (<10(
      3)). The NO(2)(-) concentrations during nitrification were generally 10 times
      higher in DB than in IB. Transient NO and N(2)O accumulation at the onset of
      denitrification was 10-10(3) times higher in DB than in IB (depending on the pH).
      The contrasting performance of DB and IB suggests that the biofilm structure,
      with anoxic/micro-oxic zones, helps to stabilize functions during anoxic spells
      and low pH.

PMID- 18616586
TI  - Phylotypes related to Ruminococcus bromii are abundant in the large bowel of
      humans and increase in response to a diet high in resistant starch.
AB  - To further understand how diets containing high levels of fibre protect against
      colorectal cancer, we examined the effects of diets high in nonstarch
      polysaccharides (NSP) or high in NSP plus resistant starch (RS) on the
      composition of the faecal microbial community in 46 healthy adults in a
      randomized crossover intervention study. Changes in bacterial populations were
      examined using denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene
      fragments. Bacterial profiles demonstrated changes in response to the consumption
      of both RS and NSP diets [analysis of similarities (ANOSIM): R=0.341-0.507,
      P<0.01]. A number of different DGGE bands with increased intensity in response to
      dietary intervention were attributed to as-yet uncultivated bacteria closely
      related to Ruminococcus bromii. A real-time PCR assay specific to the R. bromii
      group was applied to faecal samples from the dietary study and this group was
      found to comprise a significant proportion of the total community when
      individuals consumed their normal diets (4.4+/-2.6% of total 16S rRNA gene
      abundance) and numbers increased significantly (+/-67%, P<0.05) with the RS, but
      not the NSP, dietary intervention. This study indicates that R. bromii-related
      bacteria are abundant in humans and may be significant in the fermentation of
      complex carbohydrates in the large bowel.

PMID- 18616587
TI  - Haloalkaliphilic diazotrophs in soda solonchak soils.
AB  - Nitrogen fixation (NF) potential was measured in more than 40 samples of soda
      solonchak soils with the pH of water extract between 9.5 and 11.0 collected in
      several locations of Central Asia and in Egypt, using the acetylene reduction
      method. NF was detected in most of the samples. Maximal rates were observed under
      microaerophilic-anaerobic conditions with glucose as a substrate. In most cases,
      the NF negatively correlated with salt content and alkalinity. Five enrichments
      at pH 10 under micro-oxic conditions with glucose resulted in stable
      haloalkaliphilic mixed cultures, with diazotrophic component(s) active up to 2.0
      3.0 M total Na(+). The cultures were dominated by Gram-positive spore-forming
      bacteria. Molecular cloning of nifH genes demonstrated the presence of two
      phylogenetic lineages of diazotrophs in the enrichments affiliated with the low
      GC Gram-positive bacteria (in rRNA groups 1 and 6 of bacilli and in
      Clostridiales). Isolation of pure cultures of haloalkaliphilic diazotrophs from
      micro-oxic enrichments yielded nine strains, comprising two phylogenetic
      lineages. Most of the isolates (eight) were affiliated with the aerotolerant
      fermentative haloalkaliphilic bacterium Amphibacillus tropicus and a single
      strain clustered with the obligately anaerobic haloalkaliphile Bacillus
      arseniciselenatis. Diazotrophy has never been recognized previously in these
      groups of Gram-positive bacteria. Overall, the results demonstrated the
      existence, in soda solonchak soils, of a novel group of free-living fermentative
      diazotrophic bacteria active at extremely haloalkaline conditions.

PMID- 18616588
TI  - Amino acid availability determines the ratio of microcystin variants in the
      cyanobacterium Planktothrix agardhii.
AB  - Cyanobacteria are capable of producing multiple microcystin variants
      simultaneously. The mechanisms that determine the composition of microcystin
      variants in cyanobacteria are still debated. [Asp(3)]microcystin-RR contains
      arginine at the position where the more toxic [Asp(3)]microcystin-LR incorporates
      leucine. We cultured the filamentous cyanobacterium Planktothrix agardhii strain
      126/3 with and without external addition of leucine and arginine. Addition of
      leucine to the growth medium resulted in a strong increase of the
      [Asp(3)]microcystin LR/RR ratio, while addition of arginine resulted in a
      decrease. This demonstrates that amino acid availability plays a role in the
      synthesis of different microcystin variants. Environmental changes affecting cell
      metabolism may cause differences in the intracellular availability of leucine and
      arginine, which can thus affect the production of microcystin variants. Because
      leucine contains one nitrogen atom while arginine contains four nitrogen atoms,
      we hypothesized that low nitrogen availability might shift the amino acid
      composition in favor of leucine, which might explain seasonal increases in the
      [Asp(3)]microcystin LR/RR ratio in natural populations. However, when a
      continuous culture of P. agardhii was shifted from nitrogen-saturated to a
      nitrogen-limited mineral medium, leucine and arginine concentrations decreased,
      but the leucine/arginine ratio did not change. Accordingly, while the total
      microcystin concentration of the cells decreased, we did not observe changes in
      the [Asp(3)]microcystin LR/RR ratio in response to nitrogen limitation.

PMID- 18616589
TI  - Use of bromodeoxyuridine immunocapture to identify psychrotolerant phenanthrene
      degrading bacteria in phenanthrene-enriched polluted Baltic Sea sediments.
AB  - The aim of this study was to enrich and identify psychrotolerant phenanthrene
      degrading bacteria from polluted Baltic Sea sediments. Polyaromatic hydrocarbon
      (PAH)-contaminated sediments were spiked with phenanthrene and incubated for 2
      months in the presence of bromodeoxyuridine that is incorporated into the DNA of
      replicating cells. The bromodeoxyuridine-incorporated DNA was extracted by
      immunocapture and analyzed by terminal-restriction fragment length polymorphism
      and 16S rRNA gene cloning and sequencing to identify bacterial populations that
      were growing. In addition, degradation genes were quantified in the
      bromodeoxyuridine-incorporated DNA by real-time PCR. Phenanthrene concentrations
      decreased after 2 months of incubation in the phenanthrene-enriched sediments and
      this reduction correlated to increases in copy numbers of xylE and phnAc
      dioxygenase genes. Representatives of Exiguobacterium, Schewanella, Methylomonas,
      Pseudomonas, Bacteroides and an uncultured Deltaproteobacterium and a
      Gammaproteobacterium dominated the growing community in the phenanthrene-spiked
      sediments. Isolates that were closely related to three of these bacteria (two
      pseudomonads and an Exiguobacterium sp.) could reduce phenanthrene concentrations
      in pure cultures and they all harbored phnAc dioxygenase genes. These results
      confirm that this combination of culture-based and molecular approaches was
      useful for identification of actively growing bacterial species with a high
      potential for phenanthrene degradation.

PMID- 18616590
TI  - Investigation of direct vs. indirect involvement of the c-type cytochrome MacA in
      Fe(III) reduction by Geobacter sulfurreducens.
AB  - The electron transfer pathway to Fe(III) reduction in Geobacter sulfurreducens
      has been hypothesized to consist of a series of c-type cytochromes. Previous
      genetic studies suggested that the inner membrane-associated, c-type cytochrome,
      MacA, was a component of the electron transfer chain leading to Fe(III) reduction
      in the dissimilatory Fe(III)-reducer, G. sulfurreducens. However, investigation
      of the expression of OmcB, an outer-membrane c-type cytochrome demonstrated
      previously to be critical for optimal Fe(III) reduction, revealed that both omcB
      transcript and protein levels were dramatically reduced in the MacA-deficient
      mutant. Expression of the omcB gene in trans enabled the MacA-deficient mutant to
      reduce Fe(III) at a rate that was proportional to the level of omcB expression.
      These results suggest that MacA is not directly involved in electron transfer to
      Fe(III) and further confirm the importance of OmcB in Fe(III) reduction by G.
      sulfurreducens.

PMID- 18616591
TI  - The role of proteases in the differentiation of Acanthamoeba castellanii.
AB  - Proteases are significant determinants of protozoan pathogenicity and cytolysis
      of host cells. However, there is now growing evidence of their involvement in
      cellular differentiation. Acanthamoeba castellanii of the T4 genotype elaborates
      a number of proteases, which are inhibited by the serine protease inhibitor
      phenylmethylsulphonyl fluoride. Using this and other selective protease
      inhibitors, in tandem with siRNA primers, specific to the catalytic site of
      Acanthamoeba serine proteases, we demonstrate that serine protease activity is
      crucial for the differentiation of A. castellanii. Furthermore, both encystment
      and excystment of A. castellanii was found to be dependent on serine protease
      function.

PMID- 18616592
TI  - Characterization of a quinol peroxidase mutant in Aggregatibacter
      actinomycetemcomitans.
AB  - Aggregatibacter actinomycetemcomitans is an oral pathogen causing localized
      aggressive periodontitis (LAP). Recently, we characterized for the first time a
      quinol peroxidase (QPO) that catalyzes peroxidase activity using quinol in the
      respiratory chain of A. actinomycetemcomitans for the reduction of hydrogen
      peroxide. In the present study, we characterized the phenotype of a QPO null
      mutant. The QPO null mutant shows an oxidative stress phenotype, suggesting that
      QPO plays a certain role in scavenging endogenously generated reactive oxygen
      species. Notably, we discovered that the QPO null mutant exhibits a production
      defect of leukotoxin (LtxA), which is a secreted bacterial toxin and is known to
      target human leukocytes and erythrocytes. This result suggests that QPO would be
      considered as a potential drug target to inhibit the expression of LtxA from A.
      actinomycetemcomitans for the treatment and prevention of LAP.

PMID- 18616593
TI  - Rhizobial secreted proteins as determinants of host specificity in the rhizobium
      legume symbiosis.
AB  - Rhizobia are Gram-negative bacteria than can elicit the formation of specialized
      organs, called root nodules, on leguminous host plants. Upon infection of the
      nodules, they differentiate into nitrogen-fixing bacteroids. An elaborate signal
      exchange precedes the symbiotic interaction. In general, both rhizobia and host
      plants exhibit narrow specificity. Rhizobial factors contributing to this
      specificity include Nod factors and surface polysaccharides. It is becoming
      increasingly clear that protein secretion is important in determining the outcome
      of the interaction as well. This paper discusses our current understanding of the
      symbiotic role played by rhizobial secreted proteins, transported both by
      secretion systems that are of general use, such as the type I secretion system,
      and by specialized, host-targeting secretion systems, such as the type III, type
      IV and type VI secretion systems.

PMID- 18616594
TI  - Degradation of fluorobiphenyl by Pseudomonas pseudoalcaligenes KF707.
AB  - The biphenyl-degrading bacterium Pseudomonas pseudoalcaligenes KF707 can use 2-
      and 4-fluorobiphenyl as sole carbon and energy sources. Accumulation of
      fluorinated catabolites was determined by fluorine-19 nuclear magnetic
      spectroscopy (19F NMR) and revealed that growth on 4-fluorobiphenyl yielded 4
      fluorobenzoate and 4-fluoro-1,2-dihydro-1,2-dihydroxybenzoate as major
      fluorometabolites; 2-fluorobenzoate and 2-fluoromuconic acid were observed in 2
      fluorobiphenyl-grown cultures. Pseudomonas pseudoalcaligenes KF707 was not able
      to use either 2- or 4-fluorobenzoate as a growth substrate. Thus, fluorobiphenyl
      is probably degraded via the classical Bph pathway to fluorobenzoate, which is
      partially transformed via the enzymes of benzoate catabolism. This is the first
      report of investigations on the growth of bacteria on fluorinated biphenyls and
      demonstrates that as with chlorobiphenyl degradation, mineralization of the
      compounds depends upon the bacterium's ability to effectively catabolize the
      halobenzoate intermediate.

PMID- 18616595
TI  - RpoS, H-NS, and DsrA influence EHEC hemolysin operon (ehxCABD) transcription in
      Escherichia coli O157:H7 strain EDL933.
AB  - Escherichia coli hemolysin, also termed alpha-hemolysin, is a virulence factor
      for extraintestinal E. coli. Hemolysin operon (hlyCABD) transcription is
      inhibited by the nucleoid-associated protein, H-NS. This inhibition is stronger
      at lower growth temperature. This study investigated transcription of the
      homologous EHEC hemolysin (enterohemolysin) operon (ehxCABD) in EHEC O157:H7
      strain EDL933. We examined the influence of H-NS, the sigma factor RpoS, and the
      small RNA DsrA, which is known to inhibit H-NS function and to stimulate RpoS
      synthesis. During growth at 30 degrees C, DsrA overexpression increased ehxA
      transcription in the wild type but not in an hns deletion mutant. During growth
      at 37 degrees C, DsrA overexpression increased ehxA transcription independent of
      hns genotype. This indicates that DsrA influences ehxCABD operon transcription by
      two different routes, one (at lower temperature) at least partially dependent on
      H-NS, and one (at higher temperature) independent of H-NS. An rpoS deletion
      mutant expressed nondetectable levels of ehxA mRNA regardless of growth
      temperature or DsrA overexpression, indicating that the RpoS sigma factor is
      essential for ehxCABD operon expression.

PMID- 18616596
TI  - Bioweathering of chrysotile by fungi isolated in ophiolitic sites.
AB  - Asbestos minerals are commonly found in serpentine rocks and because of the
      hazard to human health, research has recently focused on possible detoxification
      strategies. Some fungal species that inhabit serpentine sites (two disused
      chrysotile asbestos mines in the Western Alps) have been isolated and
      characterized in order to obtain data on their biodiversity and bioweathering
      abilities on chrysotile fibres. The three dominant species (Verticillium
      leptobactrum, Paecilomyces lilacinus and Aspergillus fumigatus) have proved to be
      able to actively remove iron from chrysotile fibres, V. leptobactrum being the
      most efficient. A wide range of serpentinicolous fungi release siderophores, iron
      chelating compounds, that could play a role in iron extraction from fibres. Iron
      removal had been correlated previously with a decrease in the toxic potential of
      fibres, and a biotechnological application of fungi can be envisaged for asbestos
      detoxification.

PMID- 18616597
TI  - Generating cell surface diversity in Candida albicans and other fungal pathogens.
AB  - The fungal cell surface contributes to pathogenesis by mediating interactions
      with host cells and eliciting host immune responses. This review focuses on the
      cell wall proteome of the major fungal pathogen Candida albicans and discusses
      how diversity at the cell surface can be introduced by altering the expression
      and structure of cell wall proteins. Remodelling the cell wall architecture is
      critical to maintain cellular integrity in response to different environments and
      stresses including challenge with antifungal drugs. In addition, the dynamic
      nature of the cell surface alters the physical properties of the fungal interface
      with host cells and thereby influences adhesion to the host and recognition by
      components of the host's immune system. Examples of the role of cell surface
      diversity in the pathogenesis of a number of microorganisms are described.

PMID- 18616598
TI  - Immunoproteomic assay of extracellular proteins in Streptococcus equi ssp.
      zooepidemicus.
AB  - A proteomic approach combining two-dimensional electrophoresis, Western blot and
      matrix-assisted laser desorption tandem time-of-flight mass spectrometry has been
      used to map the extracellular proteins of Streptococcus equi ssp. zooepidemicus
      (S. zooepidemicus) strain ATCC 35246. These bioinformatic technologies
      facilitated the identification of novel S. zooepidemicus vaccine candidate
      antigens and therapeutic agents. Despite the limitations posed by the
      unavailability of complete genome and proteome data for S. zooepidemicus, seven
      of 15 chosen immunogenic spots were successfully identified as streptococcal
      proteins (AE1 and AE4 c. 10) from homologous Streptococcus species. Among these,
      AE6 and AE7 were identified as S. zooepidemicus UDP-N-acetyl-glucosamine
      pyrophosphorylase and UDP-glucose pyrophosphorylase proteins. In addition, AE4
      was determined to be glyceraldehyde-3-phosphate dehydrogenase from Enterococcus
      faecalis. Following SIGNALIP 3.0 (http://www.cbs.dtu.dk/servicess/SignalIP)
      prediction, data suggested that AE5, AE7 and AE9 contained signal peptides. BLAST
      (http://www.sanger.ac.uk) results found that nucleotide sequences of all
      identified proteins shared high homology (> or = 65%) with S. zooepidemicus. The
      majority of proteins identified in our study remain formally unreported in S.
      zooepidemicus. However, these proteins serve a vital role in the immune system
      and reproduction of host species. Therefore, we further evaluated the proteins as
      vaccine candidates in this study.

PMID- 18616599
TI  - Demonstration of a cholesterol-dependent cytolysin in a noninsecticidal Bacillus
      sphaericus strain and evidence for widespread distribution of the toxin within
      the species.
AB  - During the course of screening Bacillus species from food and water in Norway, we
      isolated a strain of Bacillus sphaericus of DNA homology group V, not previously
      recognized to contain entomopathogenic strains, that was cytotoxic to Vero cell
      epithelia. Peptide mass fingerprinting of a protein purified from the culture
      supernatant of B. sphaericus B354 identified a cholesterol-dependent cytolysin
      (CDC) with high amino acid sequence identity with sphaericolysin, a CDC
      identified recently in B. sphaericus DNA homology group IIA. The toxin was
      haemolytic against erythrocytes from a range of species. Haemolysis was
      potentiated by dithiothreitol and inhibited by preincubation with cholesterol.
      The toxin induced lactate dehydrogenase release from Vero cells and formed pores
      in planar lipid bilayers. The distribution of CDC genes in B. sphaericus was
      examined, with CDC gene products obtained in 13 out of 17 strains representing
      four of the six DNA homology groups. Thus, we demonstrate the presence of a CDC
      in a nonentomopathogenic DNA homology group of B. sphaericus (group V) with
      typical CDC characteristics. CDCs appear to be present in a high proportion of B.
      sphaericus strains and are not restricted to group IIA insecticidal strains.

PMID- 18616600
TI  - Evidence for extracellular control of RpoS proteolysis in Escherichia coli.
AB  - The RpoS sigma factor is required for the transition of Escherichia coli into
      stationary phase, as well as adaptation to environmental stresses and nutrient
      depletion. In this study, we report that under nutrient poor conditions, RpoS
      protein accumulation in E. coli was strongly enhanced by a secreted factor.
      Expression of a single copy RpoS'-'LacZ translational fusion was activated 12
      fold by the signal, but a single copy rpoS-lacZ transcriptional fusion was only
      activated 1.6-fold. The extracellular signal activated the RpoS'-'LacZ
      translational fusion in dsrA, rprA or dsrA/rprA mutant backgrounds, but did not
      activate in an hfq mutant background. A RpoS379'-'LacZ translational fusion,
      missing the region of RpoS required for the RssB (SprE)/ClpXP-dependent
      proteolysis, was not activated by the extracellular signal. Furthermore, in a
      rssB(sprE)::Tn10 background, the presence of extracellular signal did not
      significantly activate expression above the already elevated levels. Western and
      Northern blot analysis demonstrated that the extracellular signal significantly
      increased the levels of RpoS protein, but not mRNA. The extracellular signal did
      not bind to reversed-phase C-18 columns, was dialyzable, and stable to pH 2, pH
      12 and heat. However, protease treatment drastically reduced signal activity.
      Extracellular signal activity was absent in an hldD (rfaD) mutant, but was
      present in cell lysates, suggesting that signal was unable to be exported in an
      hldD mutant.

PMID- 18616601
TI  - Lateral gene transfer of O1 serogroup encoding genes of Vibrio cholerae.
AB  - In Gram-negative bacteria, the O-antigen-encoding genes may be transferred
      between lineages, although mechanisms are not fully understood. To assess
      possible lateral gene transfer (LGT), 21 Argentinean Vibrio cholerae O-group 1
      (O1) isolates were examined using multilocus sequence typing (MLST) to determine
      the genetic relatedness of housekeeping genes and genes from the O1 gene cluster.
      MSLT analysis revealed that 4.4% of the nucleotides in the seven housekeeping
      loci were variable, with six distinct genetic lineages identified among O1
      isolates. In contrast, MLST analysis of the eight loci from the O1 serogroup
      region revealed that 0.24% of the 4943 nucleotides were variable. A putative
      breakpoint was identified in the JUMPstart sequence. Nine conserved nucleotides
      differed by a single nucleotide from a DNA uptake signal sequence (USS) also
      found in Pastuerellaceae. Our data indicate that genes in the O1 biogenesis
      region are closely related even in distinct genetic lineages, indicative of LGT,
      with a putative DNA USS identified at the defined boundary for the DNA exchange.

PMID- 18616602
TI  - Influence of BCG vaccine strain on the immune response and protection against
      tuberculosis.
AB  - The Bacille Calmette-Guerin (BCG) vaccine has been used for more than 80 years to
      protect against tuberculosis. Worldwide, over 90% of children are immunized with
      BCG, making it the most commonly administered vaccine, with more than 120 million
      doses used each year. Although new tuberculosis vaccines are under investigation,
      BCG will remain the cornerstone of the strategy to fight the worsening
      tuberculosis pandemic for the foreseeable future. The recent delineation of
      genetic differences between BCG vaccine strains has renewed interest in the
      influence of the vaccine strain on the protective efficacy against tuberculosis.
      This review critically examines the data from animal and human studies comparing
      BCG vaccine strains. Although there is good evidence to support the notion that
      the induced immune response and protection afforded against tuberculosis differs
      between BCG vaccine strains, currently, there are insufficient data to favour or
      recommend one particular strain. Identifying BCG strains with superior protection
      would have a dramatic effect on tuberculosis control at a population level: a
      small increment in protection provided by BCG immunization will prevent large
      numbers of cases of severe tuberculosis and deaths, particularly in children.

PMID- 18616603
TI  - DNA damage-induced gene expression in Saccharomyces cerevisiae.
AB  - After exposure to DNA-damaging agents, both prokaryotic and eukaryotic cells
      activate stress responses that result in specific alterations in patterns of gene
      expression. Bacteria such as Escherichia coli possess both lesion-specific
      responses as well as an SOS response to general DNA damage, and the molecular
      mechanisms of these responses are well studied. Mechanisms of DNA damage response
      in lower eukaryotes such as Saccharomyces cerevisiae are apparently different
      from those in bacteria. It becomes clear that many DNA damage-inducible genes are
      coregulated by the cell-cycle checkpoint, a signal transduction cascade that
      coordinates replication, repair, transcription and cell-cycle progression. On the
      other hand, among several well-characterized yeast DNA damage-inducible genes,
      their effectors and mechanisms of transcriptional regulation are rather
      different. This review attempts to summarize the current state of knowledge on
      the molecular mechanisms of DNA damage-induced transcriptional regulation in this
      model lower eukaryotic microorganism.

PMID- 18616604
TI  - Fermentation of cacao (Theobroma cacao L.) seeds with a hybrid Kluyveromyces
      marxianus strain improved product quality attributes.
AB  - Fermentation of Theobroma cacao (cacao) seeds is an absolute requirement for the
      full development of chocolate flavor precursors. An adequate aeration of the
      fermenting cacao seed mass is a fundamental prerequisite for a satisfactory
      fermentation. Here, we evaluated whether a controlled inoculation of cacao seed
      fermentation using a Kluyveromyces marxianus hybrid yeast strain, with an
      increased pectinolytic activity, would improve an earlier liquid drainage
      ('sweatings') from the fermentation mass, developing a superior final product
      quality. Inoculation with K. marxianus increased by one third the volume of
      drained liquid and affected the microorganism population structure during
      fermentation, which was detectable up to the end of the process. Introduction of
      the hybrid yeast affected the profile of total seed protein degradation evaluated
      by polyacrylamide gel electrophoresis, with improved seed protein degradation,
      and reduction of titrable acidity. Sensorial evaluation of the chocolate obtained
      from beans fermented with the K. marxianus inoculation was more accepted by
      analysts in comparison with the one from cocoa obtained through natural
      fermentation. The increase in mass aeration during the first 24 h seemed to be
      fundamental for the improvement of fermentation quality, demonstrating the
      potential application of this improved hybrid yeast strain with superior
      exogenous pectinolytic activity.

PMID- 18616607
TI  - Molecular phylogeny of basidiomycetous yeasts in the Cryptococcus luteolus
      lineage (Tremellales) based on nuclear rRNA and mitochondrial cytochrome b gene
      sequence analyses: proposal of Derxomyces gen. nov. and Hannaella gen. nov., and
      description of eight novel Derxomyces species.
AB  - Phylogenetic relationships among the hymenomycetous yeasts in the Cryptococcus
      luteolus lineage of the Tremellales were examined based on sequence analyses of
      the 18S rRNA gene, 26S rRNA gene D1/D2 domain, internal transcribed spacer (ITS)
      region including 5.8S rRNA gene and mitochondrial cytochrome b gene. In addition
      to the Dioszegia clade, two clades represented by Bullera mrakii and Bullera
      sinensis, respectively, were revealed to be well-separated monophyletic groups in
      the lineage. These clades also exhibited distinguishable colony characters. Two
      new genera, Derxomyces gen. nov. (type species: Derxomyces mrakii comb. nov.) and
      Hannaella gen. nov. (type species: Hannaella sinensis comb. nov.), are proposed
      to accommodate the species in the B. mrakii and B. sinensis clades, respectively.
      Mainly based on D1/D2 and ITS sequence comparison, eight novel Derxomyces species
      were recognized from ballistoconidium-forming strains isolated from plant leaves.
      The new species and their type strains are as follows: Derxomyces boekhoutii (AS
      2.3758(T)=CBS 10824(T)), Derxomyces hainanensis (AS 2.3467(T)=CBS 10820(T)),
      Derxomyces linzhiensis (AS 2.2668(T)=CBS 10827(T)), Derxomyces pseudocylindrica
      (AS 2.3778(T)=CBS 10826(T)), Derxomyces qinlingensis (AS 2.2446(T)=CBS 10818(T)),
      Derxomyces simaoensis (AS 2.3571(T)=CBS 10822(T)), Derxomyces wuzhishanensis (AS
      2.3760(T)=CBS 10825(T)) and Derxomyces yunnanensis (AS 2.3562(T)=CBS 10821(T)).

PMID- 18616605
TI  - Glucose induction pathway regulates meiosis in Saccharomyces cerevisiae in part
      by controlling turnover of Ime2p meiotic kinase.
AB  - Several components of the glucose induction pathway, namely the Snf3p glucose
      sensor and the Rgt1p and Mth1p transcription factors, were shown to be involved
      in inhibition of sporulation by glucose. The glucose sensors had only a minor
      role in regulating transcript levels of the two key regulators of meiotic
      initiation, the Ime1p transcription factor and the Ime2p kinase, but a major role
      in regulating Ime2p stability. Interestingly, Rgt1p was involved in glucose
      inhibition of spore formation but not inhibition of Ime2p stability. Thus, the
      glucose induction pathway may regulate meiosis through both RGT1-dependent and
      RGT1-independent pathways.

PMID- 18616606
TI  - Transcriptional profiling of the Candida albicans Ssk1p receiver domain point
      mutants and their virulence.
AB  - The Ssk1p response regulator of Candida albicans is required for oxidant
      adaptation, survival in human neutrophils, and virulence in a disseminated murine
      model of candidiasis. We have previously shown that the amino acid residues D556
      and D513 of the Ssk1p receiver domain are critical to the Ssk1p in oxidant stress
      adaptation and morphogenesis. Herein, transcriptional profiling is used to
      explain the oxidant sensitivity and morphogenesis defect of two point mutants
      (D556N and D513K, respectively) compared with a WT strain. In the D556N mutant,
      during oxidative stress (5 mM H(2)O(2)), a downregulation of genes associated
      with redox homeostasis and oxidative stress occurred, which accounted for about
      5% of all gene changes, including among others, SOD1 (superoxide dismutase), CAP1
      (required for some types of oxidant stress), and three genes encoding glutathione
      biosynthesis proteins (GLR1, GSH1, and GSH2). Mutant D513K was not sensitive to
      peroxide but was impaired in its yeast $/to hyphal transition. We noted
      downregulation of genes associated with morphogenesis and cell elongation.
      Virulence of each mutant was also evaluated in a rat vaginitis model of
      candidiasis. Clearance of an SSK1 null and the D556N mutants from the vaginal
      canal was significantly greater than wild type or the D513K mutant, indicating
      that a change in a single amino acid of the Ssk1p alters the ability of this
      strain to colonize the rat vaginal mucosa.

PMID- 18616608
TI  - Behavioral characterization of P311 knockout mice.
AB  - P311 is an 8-kDa protein that is expressed in many brain regions, particularly
      the hippocampus, cerebellum and olfactory lobes, and is under stringent
      regulation by developmental, mitogenic and other physiological stimuli. P311 is
      thought to be involved in the transformation and motility of neural cells;
      however, its role in normal brain physiology is undefined. To address this point,
      P311-deficient mice were developed through gene targeting and their behaviors
      were characterized. Mutants displayed no overt abnormalities, bred normally and
      had normal survival rates. Additionally, no deficiencies were noted in motor co
      ordination, balance, hearing or olfactory discrimination. Nevertheless, P311
      deficient mice showed altered behavioral responses in learning and memory. These
      included impaired responses in social transmission of food preference, Morris
      water maze and contextual fear conditioning. Additionally, mutants displayed
      altered emotional responses as indicated by decreased freezing in contextual and
      cued fear conditioning and reduced fear-potentiated startle. Together, these data
      establish P311 as playing an important role in learning and memory processes and
      emotional responses.

PMID- 18616609
TI  - Systematic analysis of emotionality in consomic mouse strains established from
      C57BL/6J and wild-derived MSM/Ms.
AB  - Consomic strains have recently attracted attention as an advantageous method to
      screen for genes related to developmental, physiological, and behavioral
      phenotypes. Recently, a new set of consomic strains was established from the
      Japanese wild-derived mouse strain MSM/Ms and C57BL/6JJcl. By analyzing the
      entire consomic panel, we were able to identify a number of chromosomes
      associated with anxiety-like behaviors in the open-field (OF) test, a light-dark
      box and an elevated plus maze. Detailed observation of the OF behavior allowed us
      to identify chromosomes associated with those ethological traits, such as stretch
      attend, rearing, and jumping. Repeated OF test trials have different meanings for
      animals, and we found that some chromosomes responded to only the first or second
      trial, while others were consistent across both trials. By examining both male
      and female mice, sex-dependent effects were found in several measurements.
      Principal component analysis of anxiety-like behaviors extracted five factors:
      'general locomotor activity', 'thigmotaxis', 'risk assessment', 'open-arm
      exploration' and 'autonomic emotionality'. We mapped chromosomes associated with
      these five factors of emotionality.

PMID- 18616610
TI  - Genetic susceptibility to obsessive-compulsive hoarding: the contribution of
      neurotrophic tyrosine kinase receptor type 3 gene.
AB  - Recent work suggests that neurotrophic factors may contribute to the genetic
      susceptibility to obsessive-compulsive disorder (OCD). Among other clinical
      dimensions, the presence of hoarding obsessions and compulsions has been shown to
      be correlated with a number of clinical and neuroimaging findings, as well as
      with a different pattern of genetic inheritance. We used a linkage disequilibrium
      (LD)-mapping approach to investigate whether neurotrophic tyrosine kinase
      receptor type 3 (NTRK3), the high-affinity receptor of neurotrophin 3 (NT-3),
      plays a role in increasing susceptibility to hoarding in OCD. We performed an
      association study of 52 tag single nucleotide polymorphisms (tagSNPs) covering
      the whole NTRK3 gene in a sample comprising 120 OCD patients and 342 controls.
      Single nucleotide polymorphism association and haplotype analysis were performed.
      Thirty-six of our patients (30%) exhibited significant hoarding obsessions and
      compulsions. A significant association of two SNPs in the 3' downstream region of
      NTRK3 gene and obsessive-compulsive hoarding was identified: rs1017412 [odds
      ratio (OR) = 2.16; P = 0.001] and rs7176429 (OR = 2.78; P = 0.0001), although
      only the latter remained significant after Bonferroni correction. Although the
      haplotype analysis did not show significant results, a more extended block of LD
      in the OCD hoarders with respect to the control group was observed, suggesting a
      lower haplotype diversity in these individuals. Our findings suggest that NTRK3
      may contribute to the genetic susceptibility to hoarding in OCD and may
      constitute an interesting gene to focus on in studies of the genetic basis of
      obsessive-compulsive hoarding.

PMID- 18616612
TI  - SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and
      altered emotional behaviors.
AB  - SK3 K(+) channels influence neuronal excitability and are present in 5
      hydroxytryptamine (5-HT) and dopamine (DA) nuclei in the brain stem. We therefore
      hypothesized that SK3 channels affect 5-HT and DA neurotransmission and
      associated behaviors. To explore this, we used doxycycline-induced conditional
      SK3-deficient (T/T) mice. In microdialysis, T/T mice had elevated baseline levels
      of striatal extracellular DA and the metabolites dihydroxyphenylacetic acid and
      homovanillic acid. While baseline hippocampal extracellular 5-HT was unchanged in
      T/T mice, the 5-HT response to the 5-HT transporter inhibitor citalopram was
      enhanced. Furthermore, baseline levels of the 5-HT metabolite 5
      hydroxyindoleacetic acid were elevated in T/T mice. T/T mice performed equally to
      wild type (WT) in most sensory and motor tests, indicating that SK3 deficiency
      does not lead to gross impairments. In the forced swim and tail suspension tests,
      the T/T mice displayed reduced immobility compared with WT, indicative of an
      antidepressant-like phenotype. Female T/T mice were more anxious in the zero
      maze. In contrast, anxiety-like behaviors in the open-field and four-plate tests
      were unchanged in T/T mice of both sexes. Home cage diurnal activity was also
      unchanged in T/T mice. However, SK3 deficiency had a complex effect on activity
      responses to novelty: T/T mice showed decreased, increased or unchanged activity
      responses to novelty, depending on sex and context. In summary, we report that
      SK3 deficiency leads to enhanced DA and 5-HT neurotransmission accompanied by
      distinct alterations in emotional behaviors.

PMID- 18616611
TI  - Savings and extinction of conditioned eyeblink responses in fragile X syndrome.
AB  - The fragile X syndrome (FRAXA) is the most widespread heritable form of mental
      retardation caused by the lack of expression of the fragile X mental retardation
      protein (FMRP). This lack has been related to deficits in cerebellum-mediated
      acquisition of conditioned eyelid responses in individuals with FRAXA. In the
      present behavioral study, long-term effects of deficiency of FMRP were
      investigated by examining the acquisition, savings and extinction of delay
      eyeblink conditioning in male individuals with FRAXA. In the acquisition
      experiment, subjects with FRAXA displayed a significantly poor performance
      compared with controls. In the savings experiment performed at least 6 months
      later, subjects with FRAXA and controls showed similar levels of savings of
      conditioned responses. Subsequently, extinction was faster in subjects with FRAXA
      than in controls. These findings confirm that absence of the FMRP affects
      cerebellar motor learning. The normal performance in the savings experiment and
      aberrant performance in the acquisition and extinction experiments of individuals
      with FRAXA suggest that different mechanisms underlie acquisition, savings and
      extinction of cerebellar motor learning.

PMID- 18616614
TI  - In vitro antibacterial activity of endotamponading gases.

PMID- 18616615
TI  - Pseudoexfoliation as a risk factor for prevalent open-angle glaucoma.
AB  - PURPOSE: To estimate the risk of open-angle glaucoma (OAG) associated with
      exposure to pseudoexfoliation (PEX) and increased intraocular pressure (IOP).
      METHODS: In 1984-86, a cross-sectional, population-based survey was conducted in
      the municipality of Tierp, central Sweden. Its target population comprised 2429
      residents aged 65-74 years. In addition to a sample of 760 people, patients
      previously diagnosed with glaucoma were examined. The prevalence of OAG in the
      target population was estimated from the prevalence in the sample and patients
      already diagnosed. A review of prevalent cases in 1984-86 was undertaken in 2006.
      RESULTS: Definite OAG was established in 77 cases, corresponding to a prevalence
      of 5.3% (95% confidence interval [CI] 4.4-6.2). Of these, 23 represented newly
      detected cases. The prevalence of PEX was 17.2% (95% CI 14.6-19.9), calculated
      from 134 cases in the population sample. When adjusting for gender, PEX was
      associated with a 4.7-fold (95% CI 2.2-9.4) increased risk of OAG. For clinical
      cases only, the risk was 16-fold (95% CI 4.8-56) greater in subjects with PEX,
      compared with those without PEX. In individuals without a previous diagnosis of
      glaucoma, an IOP > or = 20 mmHg was associated with a 9.7-fold (95% CI 3.7-27)
      increased risk, but PEX alone was not a risk factor for OAG (adjusted odds ratio
      = 0.96). CONCLUSIONS: Pseudoexfoliation was associated with OAG only in people
      previously diagnosed with the disease. In cases detected in the population-based
      survey, increased IOP was a serious risk factor.

PMID- 18616616
TI  - The relationship between Rarebit perimetry and OCT-derived retinal nerve fibre
      layer thickness in glaucoma.
AB  - PURPOSE: To examine the association between measures of neuroretinal matrix
      integrity as determined with Rarebit perimetry and optical coherence tomography
      (OCT)-derived retinal nerve fibre layer thickness. METHODS: One randomly selected
      eye of 30 White primary open-angle glaucoma patients (age: 60.9 +/- 11.7 years;
      MD: -3.2 +/- 5.1 dB) and 16 healthy White individuals (age: 33.2 +/- 6.4 years;
      MD: -0.8 +/- 0.8 dB) were included in the study. Participants underwent Rarebit
      perimetry testing (central field, software version 4) and an OCT fast retinal
      nerve fibre layer (RNFL) scan. Correlation was investigated between hemifield
      Rarebit scores and the corresponding RNFL values, as well as between global
      Rarebit scores and the respective RNFL measures. RESULTS: Statistically
      significant correlations of average hit rate (HR) < 90 and mean hit rate (MHR)
      were detected with Max-Min and average thickness (Pearson's r ranging from 0.393
      to 0.474). Number HR < 90 showed a moderate correlation only with Max-Min (r = 
      0.396, P = 0.030). Regarding the association between hemifield hit rates and the
      corresponding OCT thickness parameters, only inferior maximum correlated
      moderately with HR superior (r = 0.385, P = 0.035). A tendency was detected for
      the relationship of superior maximum with HR inferior (r = 0.345, P = 0.062). For
      the control group, no significant correlation was found for any of the global or
      hemifield indices and the corresponding thickness values. CONCLUSION: Although
      Rarebit perimetry is based on a physiological principle distinctly different from
      conventional perimetry, it provides global indicators of neuroretinal matrix
      integrity that correlate with some OCT-derived RNFL thickness measures.

PMID- 18616617
TI  - Colour Doppler imaging evaluation of blood flow parameters in the ophthalmic
      artery in acute and chronic phases of optic neuritis in multiple sclerosis.
AB  - PURPOSE: Optic neuritis (ON) is a common manifestation of multiple sclerosis
      (MS). It is caused by the immune-mediated inflammation of the optic nerve. Some
      vascular factors that may influence blood flow in the ophthalmic artery (OA) have
      also been suggested as factors in the pathogenesis of ON. The purpose of our
      study was to evaluate blood flow velocities and resistance (RI) and pulsatile
      (PI) indices in the OA in both orbits in patients in the acute and chronic phases
      of unilateral ON and to compare these with equivalent findings in healthy control
      subjects. METHODS: Orbital colour Doppler imaging (CDI) was performed in 40
      consecutive MS patients during acute unilateral ON prior to corticosteroid
      treatment. Optic neuritis was diagnosed on the basis of clinical presentation and
      facultative assessment of visual evoked potentials (VEPs). The peak systolic
      (PSV) and end-diastolic (EDV) velocities and RI and PI were measured in the OA in
      both eyes. We compared results from affected and unaffected orbits using the
      paired t-test. The same measurements were performed in 114 MS patients with a
      history of acute unilateral ON that occurred > 1 year prior to ultrasound
      examination. We also measured the same parameters in the middle cerebral arteries
      (MCAs) on both sides in all subjects in both groups. The same measurements were
      obtained in healthy controls. RESULTS: The PSV (p < 0.0001), RI (p < 0.0001) and
      PI (p < 0.0001) in the OA in the eye affected with acute ON were significantly
      higher than in the unaffected eye. There was no difference in EDV in the OA
      between affected and unaffected eyes (p > 0.05) in the group with acute ON. We
      did not observe any significant differences between eyes in either blood flow
      velocities or the RI or PI (p > 0.05) in the group in the chronic phase of ON or
      in the control group. All the parameters in the MCAs on both sides were normal in
      both the acute and chronic groups, as well as in the control group. CONCLUSIONS:
      Pathophysiological changes during acute unilateral ON influence orbital
      haemodynamics, as is indicated by increased PSV, RI and PI in the OA in eyes
      affected with ON. However, these changes do not persist over longer periods.

PMID- 18616618
TI  - A new autosomal dominant Peters' anomaly phenotype expanding the anterior segment
      dysgenesis spectrum.
AB  - PURPOSE: To test the association of genes involved in anterior segment
      development in a family with autosomal dominantly inherited Peters' anomaly (PA)
      with a unique ocular phenotype. METHODS: Six members of a five-generation family
      with PA were extensively phenotyped and linkage analysis of candidate genes,
      namely, PAX6, PITX2, FOXC1, CYP1B1 and MAF, was performed. RESULTS: The complete
      pedigree consisted of 38 members, 19 of whom were affected. The six probands
      examined had bilateral microcornea, corneal opacity, iridocorneal adhesions,
      nystagmus and strabismus, but cataract, keratolenticular adhesions, glaucoma and
      posterior embryotoxon were absent. PAX6 gene mutations had been previously
      excluded in one of the affected members. DNA markers for candidate genes CYP1B1
      on 2p22, PITX2 on 4q25, PAX6 on 11p13, MAF on 16q23 and FOXC1 on 6p25 were
      genotyped. Highly negative lod scores were obtained for all markers. CONCLUSIONS:
      The exclusion of these genes as likely candidates supports the hypothesis that
      the ocular phenotype associated with PA segregating in this family is a distinct,
      new, autosomal dominant entity in the anterior segment dysgenesis spectrum.

PMID- 18616619
TI  - Correlations between clinical and physiological consequences of the novel
      mutation R878C in a highly conserved pore residue in the cardiac Na+ channel.
AB  - AIM: We compared the clinical and physiological consequences of the novel
      mutation R878C in a highly conserved pore residue in domain II (S5-S6) of human,
      hNa(v)1.5, cardiac Na(+) channels. METHODS: Full clinical evaluation of pedigree
      members through three generations of a Chinese family combined with SCN5A
      sequencing from genomic DNA was compared with patch and voltage-clamp results
      from two independent expression systems. RESULTS: The four mutation carriers
      showed bradycardia, and slowed sino-atrial, atrioventricular and intraventricular
      conduction. Two also showed sick sinus syndrome; two had ST elevation in leads V1
      and V2. Unlike WT-hNa(v)1.5, whole-cell patch-clamped HEK293 cells expressing
      R878C-hNa(v)1.5 showed no detectable Na(+) currents (i(Na)), even with
      substitution of a similarly charged lysine residue. Voltage-clamped Xenopus
      oocytes injected with either 0.04 or 1.5 microg microL(-1) R878C-hNa(v)1.5 cRNA
      similarly showed no i(Na), yet WT-hNa(v)1.5 cRNA diluted to 0.0004-0.0008 ng
      microL(-1)resulted in expression of detectable i(Na). i(Na) was simply determined
      by the amount of injected WT-hNa(v)1.5: doubling the dose of WT-hNa(v)1.5 cRNA
      doubled i(Na). i(Na) amplitudes and activation and inactivation characteristics
      were similar irrespective of whether WT-hNa(v)1.5 cRNA was given alone or
      combined with equal doses of R878C-hNa(v)1.5 cRNA therefore excluding dominant
      negative phenotypic effects. Na(+) channel function in HEK293 cells transfected
      with R878C-hNa(v)1.5 was not restored by exposure to mexiletine (200 microM) and
      lidocaine (100 microM). Fluorescence confocal microscopy using E3-Nav1.5 antibody
      demonstrated persistent membrane expression of both WT and R878C-hNa(v)1.5.
      Modelling studies confirmed that such i(Na) reductions reproduced the SSS
      phenotype. CONCLUSION: Clinical consequences of the novel R878C mutation
      correlate with results of physiological studies.

PMID- 18616621
TI  - Impact of early surgery after aneurysmal subarachnoid haemorrhage.
AB  - OBJECTIVES: To investigate the effect of early aneurysm surgery (<72 h) on
      outcome in patients with subarachnoid haemorrhage (SAH). MATERIALS AND METHODS:
      We studied two consecutive series of patients with aneurysmal SAH [postponed
      surgery (PS) cohort, n = 118, 1989-1992: surgery was planned on day 12 and early
      surgery (ES) cohort, n = 85, 1996-1998: ES was performed only in patients with
      Glasgow Coma Scale (GCS) >13]. We used multivariable logistic regression analysis
      to assess outcome at 3 months. RESULTS: Favourable outcome (Glasgow Outcome Scale
      4 or 5) was similar in both cohorts. Cerebral ischemia occurred significantly
      more often in the ES cohort. The occurrence of rebleeds was similar in both
      cohorts. External cerebrospinal fluid (CSF) drainage was performed more often in
      the ES cohort (51% vs 19%). Patients with cisternal sum score (CSS) of
      subarachnoid blood <15 on admission [adjusted odds ratio (OR) for favourable
      outcome: 6.4, 95% confidence interval (CI) 1.0-39.8] and patients with both CSS
      <15 and GCS > 12 on admission benefited from the strategy including ES (OR 10.5,
      95% CI 1.1-99.4). CONCLUSIONS: Our results support the widely adopted practice of
      ES in good-grade SAH patients.

PMID- 18616622
TI  - Retention rates of new antiepileptic drugs in localization-related epilepsy: a
      single-center study.
AB  - OBJECTIVES: We evaluated long-term retention rates of newer antiepileptic drugs
      (AED) in adults with localization-related epilepsy retrospectively. METHODS: We
      estimated retention rates by Kaplan-Meier method in all 222 patients (age > or =
      16) with localization-related epilepsy exposed to new AED at the Tampere
      University Hospital. RESULTS: There were 141 patients exposed to lamotrigine, 78
      to levetiracetam, 97 to topiramate, 68 to gabapentin, and 69 to tiagabine. Three
      year retention rate for lamotrigine was 73.5%, levetiracetam 65.4%, topiramate
      64.2%, gabapentin 41.7%, and tiagabine 38.2%. The most common cause for
      withdrawal of these AED was lack of efficacy. CONCLUSIONS: Our study suggests
      that there are clinically significant differences among gabapentin, lamotrigine,
      levetiracetam, tiagabine, and topiramate as treatment for focal epilepsy in
      everyday practice. Gabapentin and tiagabine seem to be less useful than the other
      three AED. Furthermore, our study supports the value of retention rate studies in
      assessing outcome of the drugs in clinical practice.

PMID- 18616623
TI  - SCN1A variant in a Scandinavian GEFS+ family: a wolf in sheep's clothing?

PMID- 18616624
TI  - Stroke and cancer: a review.
AB  - Stroke is a disabling disease and can add to the burden of patients already
      suffering from cancer. Several major mechanisms of stroke exist in cancer
      patients, which can be directly tumour related, because of coagulation disorders,
      infections, and therapy related. Stroke can also occur as the first sign of
      cancer, or lead to its detection. The classical literature suggests that stroke
      occurs more frequently in cancer patients than in the average population. More
      recent studies report a very similar incidence between cancer and non-cancer
      patients. However, there are several cancer-specific types and causes of stroke
      in cancer patients, which need to be considered in each patient. This review
      classifies stroke into ischaemic, haemorrhagic, cerebral venous thrombosis and
      other rarer types of cerebrovascular disease. Its aim is to identify the types of
      stroke most frequently associated with cancer, and give a practical view on the
      most common and most specific types of stroke. The diagnosis of the cause of
      stroke in cancer patients is crucial for treatment and prevention. Management of
      different stroke types will be briefly discussed.

PMID- 18616625
TI  - The important role of deep attachment in the uniform drainage of breast milk from
      mammary lobe.
AB  - AIM: To determine if the degree of attachment affects uniformity in the drainage
      of breast milk from mammary lobe during breastfeeding. METHODS: Thirty-seven
      pairs of healthy breast-fed infants and mothers were the subjects. A total of 48
      measurements were obtained. Foremilk was obtained from three nipple openings.
      After the breastfeeding session, hindmilk was sampled from the same three nipple
      openings and creamatocrit (CrCt) was measured. The difference in CrCt values of
      hindmilk, which corresponds to the degree of emptying of the lobe, and the
      difference in CrCt values between fore- and hindmilk samples (delta CrCt), which
      corresponds to the change in the degree of emptying among the lobe were
      calculated. RESULTS: The maximum difference in the CrCt value of hindmilk samples
      among nipple ducts was 7.0 +/- 4.1% in the shallow attachment (S) group (n = 23)
      and 2.9 +/- 1.2% in the deep attachment (D) group (n = 25) in the left breast and
      5.4 +/- 2.2% in the S group (n = 21) and 3.6 +/- 1.9% in the D group (n = 27) in
      the right breast. The mean maximum difference in delta CrCt values among nipple
      ducts was 7.6 +/- 2.9% and 2.6 +/- 1.3% in the left and 5.8 +/- 2.3% and 3.4 +/-
      1.4% in the right breast, in the S group and D group, respectively. These
      differences were significantly smaller in the D group than the S group (p <
      0.01). CONCLUSION: The results revealed that deep attachment is helpful in
      draining milk from all mammary lobe uniformly, which may contribute to successful
      breastfeeding.

PMID- 18616626
TI  - Individualized developmental care improves the lives of infants born preterm.

PMID- 18616627
TI  - Hereditary urea cycle diseases in Finland.
AB  - AIM: To estimate the incidence of urea cycle diseases (UCDs) in Finland and
      determine the course of the various disorders as well as the outcome. METHODS:
      The original data were collected in the years 1998-2001. The diagnoses made after
      2001, as well as the current status of the patients, were updated by surveys in
      the spring of 2007. RESULTS: We found a total of 55 cases of UCDs in Finland by
      2007: 30 cases of ornithine transcarbamylase (OTC) deficiency, 20 of
      argininosuccinate lyase (ASL) deficiency, 3 of carbamyl phosphate synthetase (CPS
      I) deficiency, 1 of type 1 citrullinaemia and 1 of argininaemia. The estimated
      total incidence of UCDs was 1:39 000. The incidences of individual disorders
      were: OTC deficiency 1:62 000, ASL deficiency 1:144 000, CPS deficiency 1:539 000
      and citrullinaemia 1:1 616 000. Eighteen (33%) of the patients with a diagnosis
      of UCD have died, most during their first hyperammonaemic crisis. One patient
      with OTC deficiency has had a liver transplant. Neurological symptoms of varying
      severity are common among these patients, particularly those with ASL deficiency.
      CONCLUSION: The first survey on the incidence of UCDs in Finland shows some
      differences in the occurrence rates compared to other countries. Hyperammonaemia,
      and the neurological symptoms caused by it, can be avoided in most patients with
      late-onset UCDs with a standard treatment. However, in patients with ASL
      deficiency, the development of neurological symptoms seems to be inevitable in
      spite of careful treatment and avoidance of hyperammonaemia.

PMID- 18616628
TI  - Diagnosis on a positive fashion of nonorganic failure to thrive.
AB  - AIMS: To study the predictive value of predefined symptoms and signs for
      allocating children into one of two groups: nonorganic and organic failure to
      thrive. PATIENTS AND METHODS: Two hundred eight outpatients (6 months-14 years
      old) suffering from failure to thrive (FTT) were included in the study.
      Predefined symptoms and signs were considered as potential predictors of
      organic/nonorganic failure to thrive. All patients underwent an established
      diagnostic work up in order to exclude organic causes of FTT. RESULTS: The
      percentage of patients without any organic symptom (negative predictive value),
      who were diagnosed as NOFTT was 92%; the percentage of patients having nonorganic
      symptoms only (positive predictive value), who were diagnosed as NOFTT was 96%,
      while their absence does not exclude a NOFTT diagnosis as well (negative
      predictive value = 41%). CONCLUSION: The detection of at least one nonorganic
      symptom or sign, with the exclusion of any organic symptom, can support a
      diagnosis of nonorganic FTT and therefore only few laboratory investigations seem
      to be warranted.

PMID- 18616629
TI  - Intravenous immune globulin reduces the need for exchange transfusions in Rhesus
      and AB0 incompatibility.
AB  - AIM: To conduct a quality control review of a single institution experience with
      intravenous immune globulin in the treatment of Rhesus and AB0 incompatibility.
      METHODS: Intravenous immune globulin as treatment for Rhesus and AB0
      incompatibility was introduced in our hospital in 1998. We performed a chart
      review of 176 infants with Rhesus or AB0 incompatibility treated in our hospital
      between 1993 and 2003, divided into a historical control group (1993-1998) and a
      treatment group (1999-2003). The project was approved through institutional
      ethics procedures. RESULTS: The use of exchange transfusion as a therapeutic
      modality was significantly reduced in the cohort treated with intravenous immune
      globulin (OR 0.11; 95% CI 0.046-0.26, p < 0.001). We found no difference between
      the intravenous immune globulin group and the infants receiving only exchange
      transfusion as far as the duration of phototherapy. Infants with Rhesus
      incompatibility had a higher need for top-up transfusions than those with AB0
      incompatibility. CONCLUSION: This study supports the evidence from previous
      studies suggesting that intravenous immune globulin significantly reduces the
      need for exchange transfusion in infants with Rhesus and AB0 incompatibility.

PMID- 18616630
TI  - Congenital toxoplasmosis: the importance of the western blot method to avoid
      unnecessary therapy in potentially infected newborns.

PMID- 18616631
TI  - Male circumcision through the ages: the role of tradition.
AB  - AIM: In this study, we examine the evolution of tradition concerning infant male
      circumcision, utilizing evidence from classical medical texts as well as
      information from literature, legal sources and art. METHODS: We examined the
      differences in the representation of male circumcision between ancient times and
      the modern era. RESULTS: Through the ages, male circumcision has been differently
      represented, and at present an interesting representation is born following the
      natural evolution of society. CONCLUSION: Based on the fact that the foreskin is
      not a defect, the impact of male circumcision is on the child's rights and its
      role during first years of life still remains controversial.

PMID- 18616632
TI  - Does circumcision increase neonatal jaundice?
AB  - PURPOSE: The aim of this study was to evaluate the effects of circumcision done
      during the early newborn period on the baby's feeding frequency and therefore a
      possible effect on serum bilirubin values. METHODS: Sixty consecutive male
      patients, of whom 30 were circumcised, were comparatively followed. Babies born
      between 35 and 40 gestational weeks, weighing above 3000 g and who had no
      antenatal and/or perinatal problems were enrolled. Changes in weight, frequency
      of feeds, urination, stooling and the serum bilirubin levels were compared.
      RESULTS: There was no statistically significant difference between the two
      groups. CONCLUSION: In experienced hands, newborn circumcision on the second day
      of life is safe, does not affect babies' feeding frequency or bowel movements on
      day 3, and does not increase serum bilirubin on day 4, thus does not increase the
      risk of neonatal jaundice.

PMID- 18616633
TI  - Correlation between severity of disease and reimbursement of costs in neonatal
      and paediatric intensive care patients.
AB  - AIM: The aim of the present study was to investigate the correlation between
      neonatal, paediatric and adult disease severity scores and reimbursement by
      health insurances. METHODS: The setting was a university hospital's neonatal
      intensive care unit (NICU) and paediatric intensive care unit (PICU). We
      performed a prospective study of all patients admitted over the 3-month study
      period. Data collected included five scoring systems to predict mortality or to
      quantify disease severity (Paediatric Index of Mortality [PIM], Paediatric Risk
      of Mortality [PRISM], Simplified Acute Physiological Score [SAPS], Score for
      Neonatal Acute Physiology [SNAP], Therapeutic Intervention Scoring System [TISS])
      on a daily basis, the total reimbursement as calculated by the grouper according
      to the German diagnosis-related groups (DRG) system, age of the patient, length
      of stay (LOS), International Classification of Diseases (ICD)-10 and DRG
      diagnosis. Our intention was to determine the correlation between different
      neonatal, paediatric and adult scores (PIM, PRISM III, SAPS-II, SNAP, Core-10
      TISS), and reimbursement by the health insurance on the basis of the German DRG
      system in its 2005 and 2007 version. RESULTS: No positive correlation between any
      score applied and reimbursement by the health insurance could be identified.
      Reimbursement was positively correlated to the length of hospital stay. Positive
      correlations could also be shown for some of the scores among each other.
      CONCLUSION: We conclude that other scoring systems or measures of disease
      severity urgently need to be established to terminate the chronic underfunding of
      paediatric intensive care medicine in the developed countries.

PMID- 18616635
TI  - Over-expression of an S-adenosylmethionine-dependent methyltransferase leads to
      an extended lifespan of Podospora anserina without impairments in vital
      functions.
AB  - PaMTH1, a putative methyltransferase previously described to increase in
      abundance in total protein extracts during aging of Podospora anserina is
      demonstrated to accumulate in the mitochondrial cell fraction of senescent
      cultures. The protein is localized in the mitochondrial matrix and displays a
      methyltransferase activity utilizing flavonoids as substrates. Constitutive over
      expression of PaMth1 in P. anserina results in a reduced carbonylation of
      proteins and an extended lifespan without impairing vital functions suggesting a
      protecting role of PaMTH1 against oxidative stress.

PMID- 18616636
TI  - Repression of the SUMO-specific protease Senp1 induces p53-dependent premature
      senescence in normal human fibroblasts.
AB  - The proliferative lifespan of normal somatic human cells in culture terminates in
      a permanent growth-arrested state known as replicative senescence. In this study,
      we show that RNA interference-mediated repression of the genes encoding the small
      ubiquitin-related modifier (SUMO)-specific proteases, Senp1, Senp2, and Senp7,
      induced low passage primary human fibroblasts to senesce rapidly. Following Senp1
      repression, we observed a global increase in sumoylated proteins and in the
      number and size of nuclear SUMO-containing promyelocytic leukemia (PML) bodies.
      SUMO/PML bodies also increased during replicative senescence. p53 transcriptional
      activity was enhanced towards known p53 target genes following repression of
      Senp1, and inhibition of p53 function prevented senescence after Senp1
      repression. These data indicate that Senp1 repression induces p53-mediated
      premature senescence and that SUMO proteases may thus be required for
      proliferation of normal human cells.

PMID- 18616637
TI  - Dysfunction of astrocytes in senescence-accelerated mice SAMP8 reduces their
      neuroprotective capacity.
AB  - Early onset increases in oxidative stress and tau pathology are present in the
      brain of senescence-accelerated mice prone (SAMP8). Astrocytes play an essential
      role, both in determining the brain's susceptibility to oxidative damage and in
      protecting neurons. In this study, we examine changes in tau phosphorylation,
      oxidative stress and glutamate uptake in primary cultures of cortical astrocytes
      from neonatal SAMP8 mice and senescence-accelerated-resistant mice (SAMR1). We
      demonstrated an enhancement of abnormally phosphorylated tau in Ser(199) and
      Ser(396) in SAMP8 astrocytes compared with that of SAMR1 control mice. Gsk3beta
      and Cdk5 kinase activity, which regulate tau phosphorylation, was also increased
      in SAMP8 astrocytes. Inhibition of Gsk3beta by lithium or Cdk5 by roscovitine
      reduced tau phosphorylation at Ser(396). Moreover, we detected an increase in
      radical superoxide generation, which may be responsible for the corresponding
      increase in lipoperoxidation and protein oxidation. We also observed a reduced
      mitochondrial membrane potential in SAMP8 mouse astrocytes. Glutamate uptake in
      astrocytes is a critical neuroprotective mechanism. SAMP8 astrocytes showed a
      decreased glutamate uptake compared with those of SAMR1 controls. Interestingly,
      survival of SAMP8 or SAMR1 neurons cocultured with SAMP8 astrocytes was
      significantly reduced. Our results indicate that alterations in astrocyte
      cultures from SAMP8 mice are similar to those detected in whole brains of SAMP8
      mice at 1-5 months. Moreover, our findings suggest that this in vitro preparation
      is suitable for studying the molecular and cellular processes underlying early
      aging in this murine model. In addition, our study supports the contention that
      astrocytes play a key role in neurodegeneration during the aging process.

PMID- 18616638
TI  - Different rates of telomere attrition in peripheral lymphocytes in a pair of
      dizygotic twins with hematopoietic chimerism.
AB  - Hematopoietic chimerism in dizygotic twins is due to placental vascular
      anastomoses and arises when hematopoietic stem cells from one twin home to the
      bone marrow of the other. We report a case of hematopoietic chimerism in a pair
      of 27-year-old dizygotic twins who each had a mixture of 46,XX and 46,XY blood
      lymphocytes, both with 98% male (XY) lymphocytes and 2% female (XX) lymphocytes.
      Analysis of telomere length by T/C FISH revealed that the female twin generally
      had longer telomeres than the male twin. Moreover, in the male sibling, the
      telomeres within the female lymphocytes were shortened to 87% of their original
      length, while the telomeres within the male lymphocytes were 33% longer in the
      female sibling. Thus, telomere length attrition in peripheral lymphocytes is
      determined mainly by the environment of the cell and less by intracellular
      factors.

PMID- 18616639
TI  - RASSF1A, BLU, NORE1A, PTEN and MGMT expression and promoter methylation in
      gliomas and glioma cell lines and evidence of deregulated expression of de novo
      DNMTs.
AB  - Methylation of CpG islands in gene promoters can lead to gene silencing. Together
      with deletion or mutation, it may cause a loss of function of tumor suppressor
      genes. RASSF1A (3p21.3), NORE1A (1q32.1) and BLU (3p21.3) have been shown to be
      downregulated by methylation in cancer, and PTEN (10q23.3) and MGMT (10q26.1) are
      located in areas commonly deleted in astrocytomas. MGMT methylation predicts a
      better response and a longer overall survival in patients with glioblastomas
      treated with temozolomide. We analyzed 53 astrocytoma samples and 10 high-grade
      glioma cell lines. Gene expression was assessed by RT-PCR. Bisulfite sequencing,
      MSP and a melting curve analysis-based real-time PCR were performed to detect
      promoter methylation. Treatments with 5'-aza-2'-deoxicitidine were applied to
      restore gene expression in cell lines. Ninety-two percent of tumor samples were
      methylated for RASSF1A, 30%-57% for BLU and 47% for MGMT, suggesting promoter
      methylation of these genes to be a common event in glioma tumorigenesis. Only 4%
      of the tumors revealed a methylated promoter for NORE1A. No association between
      methylation and loss of expression could be established for PTEN. We identified
      de novo DNMTs overexpression in a subset of tumors which may explain the
      methylation phenotype of individual gliomas.

PMID- 18616640
TI  - Incorporating marginal covariate information in a nonparametric regression model
      for a sample of R x C tables.
AB  - SUMMARY: Nonparametric regression models are proposed in the framework of
      ecological inference for exploratory modeling of disease prevalence rates
      adjusted for variables, such as age, ethnicity/race, and socio-economic status.
      Ecological inference is needed when a response variable and covariate are not
      available at the subject level because only summary statistics are available for
      the reporting unit, for example, in the form of R x C tables. In this article,
      only the marginal counts are assumed available in the sample of R x C contingency
      tables for modeling the joint distribution of counts. A general form for the
      ecological regression model is proposed, whereby certain covariates are included
      as a varying coefficient regression model, whereas others are included as a
      functional linear model. The nonparametric regression curves are modeled as
      splines fit by penalized weighted least squares. A data-driven selection of the
      smoothing parameter is proposed using the pointwise maximum squared bias computed
      from averaging kernels (explained by O'Sullivan, 1986, Statistical Science 1, 502
      517). Analytic expressions for bias and variance are provided that could be used
      to study the rates of convergence of the estimators. Instead, this article
      focuses on demonstrating the utility of the estimators in a study of disparity in
      health outcomes by ethnicity/race.

PMID- 18616641
TI  - Meta-analysis: Helicobacter pylori'test and treat' compared with empirical acid
      suppression for managing dyspepsia.
AB  - BACKGROUND: Which of Helicobacter pylori'test and treat' or empirical acid
      suppression should be preferred for the initial management of uncomplicated
      dyspepsia is controversial. Aim To conduct an individual patient data meta
      analysis of randomized controlled trials (RCTs) of 'test and treat' vs. empirical
      acid suppression in adults with uncomplicated dyspepsia in primary care. METHODS:
      Investigators provided original data sets for analysis. Effect of management
      strategy on symptom status and dyspepsia-related resource use at 12-month follow
      up was examined by pooling symptom and cost data to obtain relative risk (RR) of
      remaining symptomatic at 12 months and weighted mean difference (WMD) in costs
      between the two strategies with 95% confidence intervals (CI). RESULTS: We
      identified three eligible RCTs containing 1547 patients, 791 (51%) of whom were
      assigned to 'test and treat'. There was no difference detected in symptom-cure at
      12 months (RR = 0.99; 95% CI: 0.95-1.03). There was a nonsignificant trend
      towards cost-savings with 'test and treat' (WMD in costs = - 28.91 pound; 95% CI:
      - 68.48 pound to 10.65 pound). CONCLUSIONS: There was little difference in
      symptom-resolution or costs between the two strategies. A combination of patient
      and physician preference should determine the initial approach to the management
      of uncomplicated dyspepsia.

PMID- 18616643
TI  - Clinical trial: randomized, double-blind, placebo-controlled study of
      nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C
      genotype 4.
AB  - BACKGROUND: Nitazoxanide, licensed in the US for treatment of Cryptosporidium
      parvum and Giardia lamblia, inhibits hepatitis C virus replication in replicon
      systems. AIM: To evaluate the safety and efficacy of nitazoxanide monotherapy for
      the treatment of chronic hepatitis C. METHODS: This multicentre, randomized,
      double-blind, placebo-controlled study randomized 50 adult patients with chronic
      hepatitis C genotype 4 at three centres in Egypt to nitazoxanide 500 mg tablet or
      placebo twice daily for 24 weeks. Patients were followed up every 4 weeks during
      treatment and for 24 weeks after therapy. RESULTS: Seven of 23 patients (30.4%)
      in the nitazoxanide group achieved undetectable serum HCV RNA compared to 0 of 24
      in the placebo group during therapy (P = 0.004). Each of the seven responders had
      baseline HCV RNA levels < or =400 000 IU/mL. Six of the seven virological
      responders were followed up for 24 weeks after the end of treatment, and four
      patients (17.4% of 23 treated) had a sustained virological response. Adverse
      events were similar in the nitazoxanide and placebo groups. CONCLUSION:
      Nitazoxanide monotherapy is safe and effective in achieving sustained virological
      response in a modest number of patients with chronic hepatitis C genotype 4,
      particularly in patients with low baseline serum HCV RNA levels.

PMID- 18616644
TI  - Proton pump inhibitors reduce the long-term risk of recurrent upper
      gastrointestinal bleeding: an observational study.
AB  - BACKGROUND: Between 3% and 40% of patients surviving an episode of upper
      gastrointestinal bleeding (UGIB) experience a recurrence within 1 year. Aim To
      characterize further the recurrence rate of UGIB and to investigate the role of
      long-term acid suppressive therapy in its secondary prevention. METHODS:
      Recurrent cases of UGIB were identified among patients registered in The Health
      Improvement Network in the UK. A nested case-control analysis provided relative
      risk (RR) estimates of factors associated with recurrence. RESULTS: Of 1287
      patients included, 67 (5.2%) were identified with a recurrent UGIB episode,
      corresponding to a recurrence rate of 17.5 per 1000 person-years during a mean
      follow-up of 3 years. The greatest risk of recurrence was in patients prescribed
      the oral anticoagulant warfarin (RR: 5.38; 95% confidence interval: 2.02-14.36).
      Use of a single proton pump inhibitor (PPIs) was associated with a reduced risk
      of recurrence (RR: 0.51; 95% confidence interval: 0.26-0.99), even in patients
      taking warfarin, while current use of H(2)-receptor antagonists was not. After
      the first episode of UGIB, use of nonsteroidal anti-inflammatory drugs and
      aspirin was greatly reduced, preventing estimation of the risk associated with
      these drugs. CONCLUSION: Long-term PPI therapy reduces the risk of UGIB
      recurrence.

PMID- 18616647
TI  - Ethnic variation in lower oesophageal sphincter pressure and length.
AB  - BACKGROUND: Oesophageal manometry (OM) is used to diagnose oesophageal motor
      disorders. Normal values of OM among United States ethnic groups are only
      available for Hispanic Americans (HA). AIM: To obtain normal values of OM in
      adult African American (AA) volunteers, compare these with those obtained in HA
      and non-Hispanic white (nHw) volunteers to determine if ethnic variation in
      normal oesophageal motor function exists. METHODS: Healthy AA, HA and nHw were
      recruited from the Jacksonville metropolitan area. Ethnicity was self-reported.
      Exclusion criteria were symptoms suggestive of oesophageal disease, medication
      use or concurrent illness affecting OM. All underwent OM using a solid-state
      system with wet swallows. Resting lower oesophageal sphincter (LOS) pressure and
      LOS length were measured at mid-expiration, while per cent peristaltic
      contractions, distal oesophageal contraction velocity, amplitude and duration
      were measured after 5 cc water swallows. RESULTS: Fifty-six AA, 20 HA and 48 nHw
      were enrolled. All completed OM. AA had significantly higher resting LOS
      pressure, LOS length and distal oesophageal contraction duration than nHw (P <
      0.05). CONCLUSIONS: Significant ethnic exist in OM findings between AA and nHw.
      These underscore the need for ethnic specific reference values for OM to allow
      for correct diagnosis of oesophageal motor disorders in AA.

PMID- 18616649
TI  - Venous air embolism during the use of a Nd YAG laser.
AB  - We report a case of a 47-year-old female who suffered a cardiac arrest during sub
      mucosal diathermy of the inferior turbinate using a Nd YAG laser. The possible
      causes of the cardiac arrest are discussed. Venous air embolism due to Nd YAG
      laser was thought to be the most likely cause in this case. Although venous air
      embolism has previously been reported during nasal sinus surgery and choanal
      atresia when using a Nd YAG laser, the occurrence of this complication during a
      relatively minor surgical procedure has not previously been reported. It is
      important, therefore, to raise the awareness of this life threatening
      complication during use of a Nd YAG laser regardless of the duration of surgery.
      We recommend the use of appropriate methods and techniques to avoid this life
      threatening complication during the use of Nd YAG laser even for relatively short
      procedures.

PMID- 18616651
TI  - Validation of the NAFLD fibrosis score in a Chinese population with low
      prevalence of advanced fibrosis.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence
      worldwide. This study aimed to validate the NAFLD fibrosis score in the Chinese
      population. METHODS: NAFLD patients were prospectively recruited for liver biopsy
      and blood tests. The NAFLD fibrosis score was calculated as -1.675 + 0.037 x age
      (yr) + 0.094 x BMI (kg/m(2)) + 1.13 x impaired fasting glucose/diabetes (yes = 1,
      no = 0) + 0.99 x AST/ALT ratio-0.013 x platelet (x10(9)/L)-0.66 x albumin (g/dL).
      Advanced fibrosis was defined as stage 3 to 4 fibrosis. RESULTS: One hundred
      sixty-two patients (age 46 +/- 10 yr, male 59%) were included in the study.
      Advanced fibrosis was found in 18 (11%) patients. Only 11 of 128 patients with
      the NAFLD fibrosis score below the proposed low cutoff point (<-1.455) were under
      staged, resulting in a high negative predictive value of 91%. Only two patients
      exceeded the proposed high cutoff point (>0.676), but neither had advanced
      fibrosis. If the NAFLD fibrosis score was implemented in the Chinese population,
      79% of liver biopsies could be avoided. CONCLUSIONS: The NAFLD fibrosis score has
      high negative predictive value in excluding advanced fibrosis in the Chinese
      population, and can reduce the burden of liver biopsy in the vast majority of
      cases. Since there were few cases of advanced fibrosis in this cohort, this study
      had limited power in validating the high cutoff point.

PMID- 18616655
TI  - Recurrence of hepatitis B-related hepatocellular carcinoma is associated with
      high viral load at the time of resection.
AB  - BACKGROUND/AIMS: To identify the risk factors for recurrence of hepatitis B virus
      (HBV)-related hepatocellular carcinoma (HCC) after resection. METHODS: Seventy
      two patients who underwent liver resection for HBV-related HCC were recruited.
      Demographic, biochemical, tumor, and viral factors at the time of resection were
      evaluated by univariate and multivariate analyses to identify risk factors
      associated with recurrence after resection. RESULTS: The median follow-up period
      was 18.9 months and the median age was 53 yr, with male-to-female ratio of 59:13.
      Age >60 yr, tumor size >5 cm, poorly differentiated tumor, lymphovascular
      permeation, the presence of microsatellite lesions, alpha-fetoprotein (AFP) level
      >1,000 ng/mL and HBV viral load >2,000 IU/mL (4 log(10) copies/mL) at the time of
      tumor resection, HBV genotype C, core promoter mutations, and patients with no
      antiviral treatment after tumor resection were associated with increased
      cumulative risk of HCC recurrence. By multivariate analysis, HBV viral load
      >2,000 IU/mL (4 log(10) copies/mL) (P= 0.001, odds ratio [OR] 22.3), AFP >1,000
      ng/mL (P= 0.02, OR 7.4), tumor size >5 cm (P= 0.02, OR 5.1), and age >60 yr (P=
      0.01, OR 4) at the time of tumor resection remained to be the independent risk
      factors. CONCLUSIONS: Viral load of >2,000 IU/mL (4 log(10) copies/mL) is the
      most important correctable risk factor for HCC recurrence after resection.
      Whether antiviral therapy in these patients can decrease tumor recurrence
      requires further investigations.

PMID- 18616656
TI  - Oral spherical adsorptive carbon for the treatment of intractable anal fistulas
      in Crohn's disease: a multicenter, randomized, double-blind, placebo-controlled
      trial.
AB  - OBJECTIVES: Anal fistulas are common in individuals with Crohn's disease (CD). We
      sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120)
      (Kremezin; Kureha Corporation, Tokyo, Japan) for the treatment of intractable
      anal fistulas in patients with CD. METHODS: In this multicenter, randomized,
      double-blind, placebo-controlled trial, patients with CD and at least one active
      anal fistula under treatment were assigned to receive either AST-120 or placebo
      for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in
      the number of draining fistulas observed at both 4 and 8 wk. Remission was
      defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal
      Disease Activity Index (PDAI) and Crohn's Disease Activity Index (CDAI) were also
      assessed. RESULTS: In total, 62 patients were randomized, of whom 57 received AST
      120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group
      (37.0%) was significantly greater than that in the placebo group (10.0%) (P=
      0.025). The corresponding remission rates were 29.6% and 6.7%, respectively (P=
      0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to
      placebo (P= 0.004 and P= 0.005, respectively). CDAI was also significantly
      improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group
      (P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and
      no life-threatening adverse events were observed. CONCLUSION: AST-120 is useful
      for the control of intractable anal fistulas in CD patients.

PMID- 18616657
TI  - Deleterious effect of cirrhosis on outcomes after motor vehicle crashes using the
      nationwide inpatient sample.
AB  - OBJECTIVES: Alcohol abuse and minimal hepatic encephalopathy may predispose
      cirrhotics to a higher motor vehicle crash (MVC) rate. Cirrhotics have poor post
      trauma outcomes on small-scale studies. The aim was to examine the effect of
      cirrhosis on mortality, charges, and length of stay (LOS) after MVCs using the
      Nationwide Inpatient Sample (NIS) 2004. METHODS: NIS 2004 was queried for
      cirrhotics with MVC (C-MVC), cirrhotics only, and MVC only for demographics,
      comorbidities, hospital characteristics, and the Injury Severity Score (ISS). C
      MVC patients were compared with the other groups. Weighted uni/multivariate
      regression was performed for all MVCs (with/without cirrhosis). RESULTS: There
      were 560,080 discharges for cirrhosis only, 262,244 for MVC only, and 1,565 for C
      MVC. C-MVC patients were significantly younger (49.8 yr vs 58.6 yr, P < 0.0005)
      and had less comorbidities than cirrhosis only, but had similar mortality (C-MVC
      10.8% vs cirrhosis only 9.9%, P= 0.23). C-MVC patients (49.8 yr) were older than
      MVC only patients (43.7 yr, P < 0.0005). C-MVC patients also had significantly
      higher mortality (10.8%) compared with MVC only (3.1%, P < 0.0005) despite
      similar ISS. C-MVC patients had significantly greater LOS (9.6 days) and charges
      ($67,119) compared with both MVC only (6.2 days, $43,314) and cirrhosis only (7.4
      days, $35,522). Cirrhosis (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.5
      5.5) and age >65 yr (OR 5.2, 95% CI 4.4-6.0) were most commonly associated with
      mortality. Male sex, high ISS, self-pay, teaching, and large and urban hospitals
      were also significantly associated with mortality. On multivariate regression,
      cirrhosis was associated with greater charges and LOS. CONCLUSION: Cirrhosis is
      associated with greater mortality, LOS, and charges after MVC despite controlling
      for injury severity, comorbidities, and age in NIS 2004.

PMID- 18616658
TI  - Tegaserod treatment for dysmotility-like functional dyspepsia: results of two
      randomized, controlled trials.
AB  - OBJECTIVES: Therapies for dysmotility-like functional dyspepsia (FD) are limited.
      We studied tegaserod, a selective serotonin type 4 receptor agonist, in patients
      with FD. METHODS: Two identical multicenter, double-blind, randomized, placebo
      controlled trials enrolled women >/=18 yr with recurring mid-upper abdominal
      discomfort characterized by postprandial fullness, early satiety, and/or
      bloating. Patients were randomized to tegaserod 6 mg b.i.d. or placebo. Two
      patient-reported primary variables were assessed: percentage of days with
      satisfactory symptom relief, and symptom severity using the composite average
      daily severity score (CADSS). RESULTS: In total, 2,667 women were randomized with
      no differences between trials in terms of recruitment method, Helicobacter pylori
      status, heartburn, or medication use. Mean percentage of days with satisfactory
      symptom relief for tegaserod versus placebo in Trial 1: 32.2%versus 26.6% (95% CI
      of treatment difference 2.82, 9.27; P < 0.01), Trial 2: 31.9%versus 29.4% (95% CI
      of treatment difference -0.21, 6.53; P= 0.066). Mean CADSS in Trial 1: 3.14
      versus 3.35 (95% CI of treatment difference -0.29, -0.10; P < 0.0001), Trial 2:
      3.15 versus 3.23 (95% CI of treatment difference -0.18, 0.01; P= 0.094). Meta
      analysis showed significant benefit for both end points: increase in days with
      satisfactory relief 4.6% (95% CI 2.29, 6.96); decrease in CADSS 0.14 (95% CI
      0.21, 0.07). Treatment effect was greater in patients with severe baseline
      symptoms. Diarrhea requiring study discontinuation was more common with tegaserod
      than placebo (4.1%vs 0.3%). CONCLUSIONS: Some improvement in dysmotility-like FD
      was observed with tegaserod treatment. The clinical implication of this
      improvement is uncertain.

PMID- 18616660
TI  - Preoperative steroid use and risk of postoperative complications in patients with
      inflammatory bowel disease undergoing abdominal surgery.
AB  - CONTEXT: Corticosteroids are the mainstay of medical therapies to induce
      remission in acute episodes of inflammatory bowel disease (IBD). However,
      evidence suggests that this may increase the risk of postoperative complications
      among patients with IBD who go on to have abdominal surgery. OBJECTIVE: To
      estimate the risk of postoperative complications following abdominal surgery in
      patients with IBD on steroids at the time of abdominal surgery. DESIGN: Meta
      analysis of observational studies. METHODS: We searched medical electronic
      databases for full journal articles published after 1965 reporting on
      postoperative complications in patients with IBD undergoing abdominal surgery
      provided they compared patients treated with steroids with those not on steroids.
      We hand searched the reference lists of all retrieved articles. Two independent
      reviewers extracted data from studies meeting the inclusion criteria and any
      discrepancies were resolved by discussion. We carried out fixed effects meta
      analysis, funnel plot and sensitivity analyses. RESULTS: A total of seven
      observational studies involving 1,532 patients met the inclusion criteria for
      risk of total complications, and five observational studies involving 1,714
      patients met the inclusion criteria for risk of infectious complications. Pooled
      analysis showed an increased risk of all postoperative complications (OR 1.41,
      95% confidence interval 1.07-1.87), as well as an increased risk of postoperative
      infectious complications (OR 1.68, 95% confidence interval 1.24-2.28) among
      patients on steroids. Patients who received higher doses of perioperative oral
      steroids (>40 mg) had a higher risk of total complications (OR 2.04 (95% CI 1.28
      3.26). CONCLUSIONS: There is an increased risk of total as well as infectious
      complications following the use of steroids in patients with IBD.

PMID- 18616661
TI  - A whole genome linkage scan identifies multiple chromosomal regions influencing
      adiposity-related traits among Samoans.
AB  - We conducted a genome-wide scan in 46 pedigrees, with 671 phenotyped adults, from
      the independent nation of Samoa to map quantitative trait loci (QTLs) for
      adiposity-related phenotypes, including body mass index (BMI), abdominal
      circumference (ABDCIR), percent body fat (%BFAT), and fasting serum leptin and
      adiponectin. A set of 378 autosomal and 14 X chromosomal microsatellite markers
      were genotyped in 572 of the adults. Significant genetic correlations (0.82-0.96)
      were detected between pairs of BMI, ABDCIR, %BFAT and leptin. Suggestive linkages
      were found on 13q31 (LOD = 2.30 for leptin, LOD = 2.48 for %BFAT, LOD = 2.04 for
      ABDCIR, and LOD = 2.09 for BMI) and on 9p22 (LOD = 3.08 for ABDCIR and LOD = 2.53
      for %BFAT). Furthermore, bivariate linkage analyses indicated that the genetic
      regions on 9p22 (bivariate LOD 2.35-3.10, LOD(eq) (1df) 1.88-2.59) and 13q31
      (bivariate LOD 1.96-2.64, LOD(eq) 1.52-2.21) might harbor common major genes with
      pleiotropic effects. Other regions showing suggestive linkage included 4q22 (LOD
      = 2.95) and 7p14 (LOD = 2.64) for %BFAT, 2q13 for adiponectin (LOD = 2.05) and
      19q12 for BMI-adjusted leptin (LOD = 2.03). Further fine mapping of these regions
      may help identify the genetic variants contributing to the development of obesity
      in Samoan adults.

PMID- 18616663
TI  - Assessment of alcohol use among methadone maintenance patients by direct ethanol
      metabolites and self-reports.
AB  - BACKGROUND: Heavy alcohol consumption may accelerate the progression of hepatitis
      C (HCV)-related liver disease and/or limit efforts at antiviral treatment. As
      most of the patients in methadone maintenance treatment (MMT) suffer from
      hepatitis C infection, this study was conducted to identify the alcohol intake
      among these patients at a Swiss Psychiatric University Clinic by self-reports and
      direct ethanol metabolites as biomarkers of ethanol consumption. PATIENTS AND
      METHODS: A convenience sample of 40 MMT patients (15 women, 25 men; median age 39
      years) of the total 124 patients was asked and consented to participate in this
      study. This sample was not different in age, gender distribution, and rate of
      hepatitis C infection from the total sample. The Alcohol Use Disorders
      Identification Test (AUDIT) and self-reported ethanol intake during the previous
      7 days were assessed. In addition, ethyl glucuronide (EtG) in urine, and fatty
      acid ethyl esters (FAEEs) and EtG in hair were determined using LC-MS/MS and gas
      chromatograph/mass spectrometer. The limit of quantitation for UEtG, HEtG, and
      FAEEs were 0.1 mg/l, 2.3 pg/mg, and 0.1 ng/mg, respectively. RESULTS: Fourteen
      participants reported abstinence from alcohol for the previous 7 days. AUDIT
      scores were > or =8 in 15 male and >5 in 5 female participants. Direct ethanol
      metabolites were as follows (median, min, max, standard deviation): UEtG (19
      positives; 9.91, 1.38 to 251, 62.39 mg/l); the values of HEtG were 17.65, 0 to
      513, 105.62 pg/mg [in 2 cases no material, 8 abstinent (up to 7 pg/mg), 15 social
      drinkers (up to 50 g per day), and 15 excessive users (>50/60 g/d)]. For the 13
      cases, where enough material for additional determination of HFAEEs was
      available, the values were 0.32, 0 to 1.32, 0.44 ng/mg. Among the 30 HEtG
      positive participants, 20 had not reported the corresponding ethanol intake using
      question 1 (frequency) and 2 (quantity) of the AUDIT. Of the 14 participants
      reporting no alcohol intake during the previous 7 days, 4 were UEtG-positive.
      HEtG and AUDIT correlated significantly (r = 0.622, p < 0.0001), but this was not
      the case for UEtG and self-reported ethanol intake during the previous 7 days.
      CONCLUSION: (1) HEtG identified 20 cases of daily ethanol intake of more than 20
      g, that would have been missed by the sole use of question 1 (frequency) and 2
      (quantity) of the AUDIT. (2) Using the total score of the AUDIT, HEtG confirmed
      10 more cases positive for alcohol intake. (3) Episodic heavy drinking is with
      22.5% more frequent than in general population, and (4) of the 14 participants
      who reported no alcohol intake during the previous 7 days, 4 were UEtG positive.
      Improved detection of alcohol consumption, which is hazardous or harmful in the
      context of HCV and opiate dependence, would allow for earlier intervention in
      this population which is at particular risk of liver disease and fatal
      respiratory-depressed overdose. The combined use of self-reports and direct
      ethanol metabolites seems promising.

PMID- 18616664
TI  - Craving for alcohol and food during treatment for alcohol dependence: modulation
      by T allele of 1519T>C GABAAalpha6.
AB  - BACKGROUND: Craving for alcohol and food has been studied in association with
      alcohol dependence and eating disorders, respectively. One subclass of the gamma
      aminobutyric acid (GABA) receptor, 1519T>C GABA(A)alpha6 has been reported to be
      associated with both alcohol dependence and weight gain. In this study, we
      hypothesized that patients being treated for alcohol dependence would report
      decreased craving for alcohol, but an increased craving for food during a 4-week
      treatment period. We further hypothesized that the T allele of the 1519T>C
      GABA(A)alpha6 gene would modulate the extent of changes in craving for alcohol
      and food. METHODS: This study included 98 male inpatients being treated for
      alcohol dependence. A 7-point visual analog scale was applied to evaluate
      relative levels of alcohol and food craving at baseline and again 4 weeks later.
      Body weight was also checked at the same periods. Genotyping of the 1519T>C SNP
      in GABA(A)alpha6 was carried out by restriction fragment length polymorphism.
      RESULTS: There were significant changes in craving for alcohol and food in all
      patients with alcohol dependence. During the treatment period, body weight
      increased in all patients with alcohol dependence. Changes in alcohol and food
      craving in T-allele carriers (CT + TT) of 1519T>C GABA(A)alpha6 were greater than
      those observed in CC homozygotes. In T-allele carriers, body weight significantly
      increased and the changes in weight showed a negative correlation with the change
      in the craving for alcohol and a positive correlation with the changes in craving
      for food. DISCUSSION: The current results suggest that in T-allele carriers the
      change in craving for alcohol during treatment for alcohol dependence is
      negatively associated with changes in craving for food. The T allele of the
      1519T>C GABA(A)alpha6 gene may be one of the modulating factors associated with
      changes in craving for alcohol and food during treatment of patients with alcohol
      dependence.

PMID- 18616665
TI  - Voluntary ethanol consumption differs in adolescent and adult male rats using a
      modified sucrose-fading paradigm.
AB  - BACKGROUND: Initiation of alcohol consumption during adolescence is high, which
      usually begins with consumption of highly concentrated sweetened alcoholic
      beverages in adolescent humans. Enhanced voluntary ethanol (EtOH) intake has been
      observed previously in adolescent relative to adult rats under continuous access
      conditions using sweetened EtOH solutions. The present set of experiments
      investigated patterns of voluntary EtOH intake in adolescent and adult rats using
      sweetened EtOH solutions in a limited access paradigm. METHODS: Rats were trained
      with modified sucrose-substitution protocols that ended at either 5% sucrose-20%
      EtOH (5S/20E) (Exp. 1) or 5% sucrose-10% EtOH (5S/10E) (Exp. 2). RESULTS:
      Voluntary EtOH consumption differences between the 2 age groups were apparent at
      higher (i.e., 10 and 20%), but not lower (i.e., 2 and 5%) EtOH concentrations.
      Adolescent rats consumed more EtOH on a g/kg basis only at 20% EtOH (Exp. 1).
      Adolescent rats voluntarily consumed more EtOH than adults when maintained at
      5S/10E (Exp. 2). To assess whether these age-related differences in voluntary
      EtOH intake were concentration dependent, rats were trained with 5S/20E and
      subsequently trained with decreasing EtOH concentrations (i.e., 5S/10E and
      5S/5E). Adolescents consumed more EtOH when initially presented with the 5S/10E
      and 5S/20E EtOH concentrations, and subsequently at the lower 5S/5E EtOH
      concentration (Exp. 3). There were no differences in preference for the sucrose
      only solution, however adolescents tended to consume more sucrose at the 5S
      sucrose concentration (Exp. 4). Given that adolescents consumed more EtOH at the
      5S/10E and 5S/20E, but not at the 5S/5E EtOH concentrations, preference for
      sucrose does not solely explain the age differences in voluntary EtOH intake
      observed. CONCLUSIONS: Overall, results replicate previous work, demonstrating
      adolescent rats consume more EtOH relative to adults. However, the present
      results were observed using sweetened EtOH solutions in a limited access
      paradigm. The present modified sucrose-substitution paradigm may serve as a valid
      model of human adolescent drinking behavior.

PMID- 18616666
TI  - Adjusting alcohol quantity for mean consumption and intoxication threshold
      improves prediction of nonadherence in HIV patients and HIV-negative controls.
AB  - BACKGROUND: Screening for hazardous drinking may fail to detect a substantial
      proportion of individuals harmed by alcohol. We investigated whether considering
      an individual's usual drinking quantity or threshold for alcohol-induced
      cognitive impairment improves the prediction of nonadherence with prescribed
      medications. METHOD: Cross-sectional analysis of participants in a large, multi
      site cohort study. We used the timeline followback to reconstruct 30-day
      retrospective drinking histories and the timeline followback modified for
      adherence to reconstruct 30-day medication adherence histories among 3,152
      individuals in the Veterans Aging Cohort Study, 1,529 HIV infected and 1,623
      uninfected controls. We categorized daily alcohol consumption by using quantity
      alone, quantity after adjustment for the individual's mean daily alcohol
      consumption, and self-reported level of impairment corresponding to each
      quantity. A standard drink was defined as 14 g of ethanol. Nonadherence was
      defined as the proportion of days with > or =1 medication doses missed or taken >
      or =2 hours late, and clinically significant nonadherence was defined as > or =5%
      absolute increase in the proportion of days with nonadherence. RESULTS: The mean
      adjusted- and impairment-based methods showed greater discrimination of
      nonadherence risk compared to the measure based on quantity alone (quantity-based
      categorization, 3.2-fold increase; quantity adjusted for mean daily consumption,
      4.6-fold increase, impairment-based categorization, 3.6-fold increase). The
      individualized methods also detected greater numbers of days with clinically
      significant nonadherence associated with alcohol. Alcohol was associated with
      clinically significant nonadherence at a lower threshold for HIV infected versus
      uninfected patients (2 standard drinks vs. 4 standard drinks) using quantity
      based categorization, but this difference was no longer apparent when
      individualized methods were used. CONCLUSIONS: Tailoring screening questions to
      an individual's usual level of alcohol consumption or threshold for impairment
      improves the ability to predict alcohol-associated medication nonadherence.

PMID- 18616668
TI  - Emerging role of epigenetics in the actions of alcohol.
AB  - This review deals with the recent developments on the epigenetic effects of
      ethanol. A large body of data have come from studies in liver and in neuronal
      systems and involve post-translational modifications in histones and methylations
      in DNA. Ethanol causes site selective acetylation, methylation, and
      phosphorylation in histone. With respect to methylations the methyl group
      donating system involving S-adenosyl methionine appears to play a central role.
      There is contrasting effect of acetylation versus methylation on the same site of
      histone, as it relates to the transcriptional activation. Epigenetic memory also
      appears to correlate with liver pathology and Mallory body formation.
      Experimental evidence supports transcriptional regulation of genes in the CNS by
      DNA methylations. These studies are contributing towards a better understanding
      of a novel epigenetic regulation of gene expression in the context of alcohol.
      The critical steps and the enzymes (e.g., histone acetyltransferase, histone
      deacetylase, DNA methyltransferase) responsible for the epigenetic modifications
      are prime targets for intense investigation. The emerging data are also beginning
      to offer novel insight towards defining the molecular actions of ethanol and may
      contribute to potential therapeutic targets at the nucleosomal level. These
      epigenetic studies have opened up a new avenue of investigation in the alcohol
      field.

PMID- 18616667
TI  - Insulin and insulin-like growth factor resistance in alcoholic neurodegeneration.
AB  - BACKGROUND: Chronic alcohol feeding of adult Long Evans rats causes major central
      nervous system abnormalities that link neuronal loss and impaired acetylcholine
      homeostasis to ethanol inhibition of insulin and insulin-like growth factor (IGF)
      signaling and increased oxidative stress. OBJECTIVES: We now characterize the
      integrity of insulin and IGF signaling mechanisms and assess molecular indices of
      neurodegeneration in the cerebellar vermis and anterior cingulate gyrus of human
      alcoholics. RESULTS: Alcoholic cerebella had increased neuronal loss, gliosis,
      lipid peroxidation, and DNA damage relative to control. Quantitative RT-PCR
      studies demonstrated reduced expression of insulin, insulin receptor and IGF-II
      receptor in the anterior cingulate, and reduced expression of insulin, IGF-I, and
      their corresponding receptors in the vermis. Competitive equilibrium binding
      assays revealed significantly reduced specific binding to the insulin, IGF-I, and
      IGF-II receptors in both the anterior cingulate and vermis of alcoholic brains.
      These effects of chronic alcohol abuse were associated with significantly reduced
      expression of choline acetyltransferase, which is needed for acetylcholine
      biosynthesis. CONCLUSIONS: The results suggest that alcoholic neurodegeneration
      in humans is associated with insulin and IGF resistance with attendant impairment
      of neuronal survival mechanisms and acetylcholine homeostasis.

PMID- 18616670
TI  - Glutamate export at the choroid plexus in health, thiamin deficiency, and ethanol
      intoxication: review and hypothesis.
AB  - INTRODUCTION: The earliest observed effect in the pathogenesis of experimental
      Wernicke's encephalopathy and of ethanol intoxication in rats is impairment of
      the blood cerebrospinal fluid (CSF) barrier at the choroid plexus (CP). For an
      explanation, these observations direct attention to the role of the CP in
      maintaining glutamate homeostasis in the CSF. METHODS: Characteristics of the CP
      epithelium (CPE) are reviewed, focusing on its role in removal of glutamate from
      the CSF and its potential for impairment by ethanol oxidation or by thiamin
      deficient glucose oxidation. RESULTS: The export of glutamate from CSF to blood
      at the CP is energy dependent, saturable, and stereospecific. However, the
      incapacity of the CP to convert glutamate to other metabolites makes it
      vulnerable to glutamate accumulation should alpha-ketoglutarate dehydrogenase
      activity be decreased. Elsewhere ethanol metabolism and thiamin-deficiency
      independently decrease the activity of this mitochondrial enzyme. We argue that
      they have the same effect within the mitochondria-rich CPE, thereby decreasing
      energy production necessary for export of glutamate from CSF to blood; diverting
      its energy metabolism to further glutamate production; and impairing its blood
      CSF barrier function. This impairment appears to be mediated by glutamate and is
      attenuated by MK801 but whether it involves one of the CPE glutamate receptors is
      yet uncertain. This impairment exposes the CSF and hence the paraventricular
      brain extracellular fluid to neuroactive substances from the blood, including
      further glutamate, explaining the paraventricular location of neuropathology in
      Wernicke's encephalopathy. Other organs normally protected from blood by a
      barrier are affected also by ethanol abuse and by thiamin deficiency, namely the
      eye, peripheral nerves, and the testis. Much less is known regarding the function
      of these barriers. CONCLUSIONS: Impairment of the CP by ethanol intoxication and
      by thiamin-deficient carbohydrate metabolism has a common, rational explanation
      that can guide future research.

PMID- 18616669
TI  - Chronic alcohol consumption generates a vulnerable immune environment during
      early SIV infection in rhesus macaques.
AB  - BACKGROUND: Alcohol consumption is a common problem in HIV-infected individuals,
      and the effects of alcohol may alter the efficiency of the immune response,
      potentially aggravating the disease as well as affecting end organs, such as the
      brain. However, the elements of the virus-host interaction that are modulated by
      ethanol are poorly dissected. METHODS: Ethanol intake was conditioned in rhesus
      macaques prior to SIV infection, in order to mimic this common human behavior,
      and allow the evaluation of aspects of the virus-immune system interactions
      during acute time-points, when important facets of the infection are set up and
      when virus reproducibly enters the brain. RESULTS: Although ethanol had a limited
      effect on the acute plasma viral load, it resulted in reduced circulating memory
      CD4(+) T cells and increased levels of monocytes expressing the viral coreceptor
      CCR5. In organs, ethanol consumption impacted immune cells in the liver as well
      as lymphoid and other nonlymphoid tissues, where CD4(+) T cells were
      predominantly affected. CONCLUSION: Overall, the consumption of alcohol causes
      immune cell alterations that can contribute to the generation of a disease
      susceptible environment upon SIV infection.

PMID- 18616671
TI  - Choroid plexus dysfunction: the initial event in the pathogenesis of Wernicke's
      encephalopathy and ethanol intoxication.
AB  - BACKGROUND: In both acute ethanol intoxication and in thiamin deficient glucose
      metabolism, previous studies have detected blood-brain barrier (BBB) and/or blood
      CSF-barrier (BCSFB) impairment but were unable to assess their significance in
      relation to other changes in the brain. METHODS: Contrast-enhanced, magnetic
      resonance imaging (MRI) was used to detect and time any impairment of the BBB or
      BCSFB in rats given an acute ethanol load or in rats made thiamin deficient to
      the point of mild ataxia and then given an acute glucose load. RESULTS: The BCSFB
      at the choroid plexus (CP) was impaired within 10 minutes by either (i) a single
      i.p. dose of glucose in thiamin-deficiency, an effect that was attenuated by
      prior MK801 and preceded the published onset of exacerbation of motor
      incoordination and elevation of brain glutamate derivatives; or (ii) a single
      i.p. dose of ethanol in thiamin-sufficiency, an effect that was proportional to
      the blood alcohol concentration and preceded the published onset of signs of
      intoxication. In contrast to the BCSFB, the BBB remained intact throughout the 90
      minutes period of these experiments. CONCLUSIONS: In both ethanol intoxication
      and thiamin-deficient glucose metabolism, BCSFB impairment exposes the CSF and
      hence the brain extracellular fluid to neuroactive substances from the blood. CP
      impairment is the earliest detected event in both these animal models; and
      explains the paraventricular location of WE neuropathology and why WE is
      associated with, but not dependent on, alcoholism.

PMID- 18616673
TI  - Specific reduction of alcohol's motivational properties by the positive
      allosteric modulator of the GABAB receptor, GS39783--comparison with the effect
      of the GABAB receptor direct agonist, baclofen.
AB  - BACKGROUND: Activation of the GABA(B) receptor--either by means of direct
      agonists (like baclofen) or positive allosteric modulators (like GS39783)--has
      been observed to suppress alcohol drinking and reinforcement in rats and mice.
      The present study was conducted to assess and compare the effect of baclofen and
      GS39783 on the motivational properties of alcohol. METHODS: Selectively bred
      Sardinian alcohol-preferring (sP) rats were initially trained to respond on a
      lever (on an fixed ratio 4 schedule of reinforcement) to orally self-administer
      alcohol (15%, v/v) or sucrose (3%, w/v) in daily 30-minute sessions. Once lever
      responding reached stable levels, rats were exposed to sessions with a
      progressive ratio schedule of reinforcement. The effect of nonsedative doses of
      baclofen (0, 1, and 3 mg/kg, i.p.) and GS39783 (0, 25, 50, and 100 mg/kg, i.g.)
      on breakpoint for alcohol and sucrose (defined as the lowest response requirement
      not achieved by each rat and used as index of the motivational strength of
      alcohol and sucrose) was determined. RESULTS: Baclofen administration resulted in
      a dose-dependent decrease in breakpoint for alcohol; this effect was not
      specific, as baclofen also reduced--to a comparable extent--breakpoint for
      sucrose. Conversely, GS39783 administration resulted in a dose-dependent and
      completely specific reduction in breakpoint for alcohol. CONCLUSIONS: The present
      results (i) confirm previous data on baclofen's capacity to suppress, although
      nonspecifically, alcohol's motivational properties, and (ii) extend to alcohol's
      motivational properties the capacity of GS39783 to inhibit alcohol drinking and
      reinforcement in rats.

PMID- 18616672
TI  - Acute alcohol intake induces SOCS1 and SOCS3 and inhibits cytokine-induced STAT1
      and STAT3 signaling in human monocytes.
AB  - BACKGROUND: Acute alcohol consumption is associated with induction of immuno
      inhibitory cytokines and down-regulation of pro-inflammatory responses to various
      pathogens. We previously reported that alcohol activates janus kinase/signal
      transducer and activator of transcription (JAK/STAT) signaling leading to IL-10
      induction. The JAK-STAT pathway also activates its own negative regulators,
      suppressors of cytokine signaling (SOCS) 1 and SOCS3. SOCS proteins are inducible
      inhibitors that negatively regulate STAT3/STAT1 signaling pathways induced by
      cytokines, IL-6 or IFNs. Here we aimed to explore the effect of acute alcohol on
      induction of SOCS1/SOCS3 and regulation of STAT3/STAT1 pathways induced by IL-6
      or IFNs in human monocytes. METHODS: Blood samples from normal volunteers were
      collected before and 24 hours after consumption of 2 ml vodka/kg body weight. For
      in vitro experiments human monocytes were pretreated with ethanol (EtOH) followed
      by stimulation with cytokines; proteins were analyzed by Western blot, nuclear
      protein binding to DNA by EMSA, and RNA by real time PCR. RESULTS: Acute in vivo
      or in vitro alcohol treatment increased both SOCS1 and SOCS3 RNA expression in
      monocytes. Alcohol treatment resulted in increased STAT3 and STAT1 DNA binding
      capacity. Activation of both STAT1 and STAT3 has been shown to induce SOCS1/3. We
      hypothesized that induction of SOCS proteins by alcohol in turn may lead to
      modulation of cytokine signaling through STAT1 and STAT3. Indeed, we observed
      significant down-regulation of IL-6-, IFNalpha- and IFNgamma-induced STAT1 DNA
      binding as well as inhibition of IL-6- and IFNgamma-induced STAT3 when alcohol
      was added to monocytes 3 hours prior to the cytokine stimulation. Consistent with
      inhibition of IL-6-induced STAT3 DNA binding in alcohol-pretreated cells, the
      levels of IL-6-dependent genes, MCP-1 and ICAM-1, was reduced after IL-6
      stimulation. Similar to EtOH alone, combined EtOH+IL-6 simulation resulted in
      increased expression of both SOCS3 and SOCS1 genes. CONCLUSION: While acute
      alcohol treatment alone activates STAT1/3 signaling pathways and induces SOCS3
      and SOCS1 levels in monocytes, alcohol also leads to down-regulation of IL-6-,
      IFNalpha-, and IFNgamma-induced signaling via STAT1/STAT3 pathways, likely
      through excessive SOCS activation.

PMID- 18616674
TI  - Alcohol content variation of bar and restaurant drinks in Northern California.
AB  - OBJECTIVE: To estimate the average of and sources of variation in the alcohol
      content of drinks served on premise in 10 Northern Californian counties. METHODS:
      Focus groups of bartenders were conducted to evaluate potential sources of drink
      alcohol content variation. In the main study, 80 establishments were visited by a
      team of research personnel who purchased and measured the volume of particular
      beer, wine, and spirit drinks. Brand or analysis of a sample of the drink was
      used to determine the alcohol concentration by volume. RESULTS: The average wine
      drink was found to contain 43% more alcohol than a standard drink, with no
      difference between red and white wine. The average draught beer was 22% greater
      than the standard. Spirit drinks differed by type with the average shot being
      equal to one standard drink while mixed drinks were 42% greater. Variation in
      alcohol content was particularly wide for wine and mixed spirit drinks. No
      significant differences in mean drink alcohol content were observed by county for
      beer or spirits but one county was lower than two others for wine. CONCLUSIONS:
      On premise drinks typically contained more alcohol than the standard drink with
      the exception of shots and bottled beers. Wine and mixed spirit drinks were the
      largest with nearly 1.5 times the alcohol of a standard drink on average.
      Consumers should be made aware of these substantial differences and key sources
      of variation in drink alcohol content, and research studies should utilize this
      information in the interpretation of reported numbers of drinks.

PMID- 18616675
TI  - Salivary acetaldehyde concentration according to alcoholic beverage consumed and
      aldehyde dehydrogenase-2 genotype.
AB  - BACKGROUND: Acetaldehyde is suspected of playing a critical role in cancer
      development in the upper aerodigestive tract (UADT). The high salivary
      acetaldehyde levels after alcohol drinking are partly due to acetaldehyde
      production by oral bacteria. Some alcoholic beverages, especially Calvados and
      shochu, contain very high levels of acetaldehyde. Inactive heterozygous aldehyde
      dehydrogenase-2 (ALDH2) increases the risk of UADT cancer in drinkers. METHODS:
      In a randomized cross-over design study, 19 healthy Japanese volunteers ingested
      0.6 g ethanol/kg body weight in the form of 13% ethanol Calvados, 13% ethanol
      shochu, 13% ethanol red wine, and 5% ethanol beer under the fasting conditions at
      3-week intervals. We monitored blood and salivary acetaldehyde concentrations
      immediately after drinking, and 30, 60, 90, 120, and 180 minutes after completion
      of drinking. RESULTS: The acetaldehyde concentration of each beverage was:
      Calvados 0.60 mM (1.86 mM in 40% undiluted solution), shochu 0.60 mM (1.16 mM in
      25% undiluted solution), red wine 0.25 mM, and beer 0.14 mM. The salivary
      acetaldehyde concentration immediately after drinking wine was significantly
      lower than the other beverages, and it was significantly lower immediately after
      drinking beer than Calvados. The acetaldehyde concentrations 30 to 180 minutes
      after drinking were unrelated to the beverage type. Throughout the observation
      period the salivary acetaldehyde concentrations were much higher than the blood
      acetaldehyde concentrations in all 12 active ALDH2 homozygotes (24 to 53 microM
      in saliva vs. 2 to 5 microM in blood) and in all 7 inactive ALDH2 heterozygotes
      (37 to 76 microM in saliva vs. 12 to 25 microM in blood), and they were 13 to 25
      microM higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes after
      adjusting for age, body weight, sex, smoking and drinking habits, and time since
      the last toothbrushing. The values after subtracting the blood acetaldehyde
      concentration from the salivary acetaldehyde concentration were also higher in
      the ALDH2 heterozygotes than in the ALDH2 homozygotes. CONCLUSIONS: There are
      differences in exposure of the UADT to high salivary acetaldehyde concentrations
      according to the type of alcoholic beverage and ALDH2 genotype, and the
      differences partly explain the differences in the cancer susceptibility of the
      UADT according to alcoholic beverage and ALDH2 genotype.

PMID- 18616676
TI  - Chronic inflammation in asthma: a contest of persistence vs resolution.
AB  - Recent investigations have highlighted that endogenous anti-inflammatory
      mediators and immune regulating mechanisms are important for the resolution of
      inflammatory processes. A disruption of these mechanisms can be causally related
      not only to the initiation of unnecessary inflammation, but also to the
      persistence of several chronic inflammatory diseases. In asthma, chronic Th-2
      driven eosinophilic inflammation of the airways is one of the central
      abnormalities. To date, elucidating the role of the different pro-inflammatory
      mediators involved in orchestrating the inflammatory processes in asthma has been
      the subject of intense research in both humans and animal models. However, the
      counter-regulatory mechanisms that co-determine the outcome in the contest of
      resolution vs persistence of the eosinophilic airway inflammation remain poorly
      understood. These are currently being investigated in animal models of chronic
      asthma. Elucidating these mechanisms is of relevance, since it can give rise to a
      new therapeutic approach in the treatment of chronic airway inflammation in
      asthmatics. This novel concept of treatment involves the stimulation of
      endogenous anti-inflammatory pathways, rather than solely antagonising the
      various pro-inflammatory mediators. Here, we review and discuss the current
      knowledge about these endogenous anti-inflammatory mediators in clinical and
      experimental asthma.

PMID- 18616677
TI  - Mouse allergen exposure, wheeze and atopy in the first seven years of life.
AB  - BACKGROUND: Little is known about mouse allergen exposure in home environments
      and the development of wheezing, asthma and atopy in childhood. OBJECTIVE: To
      examine the relation between mouse allergen exposure and wheezing, atopy, and
      asthma in the first 7 years of life. METHODS: Prospective study of 498 children
      with parental history of allergy or asthma followed from birth to age 7 years,
      with longitudinal questionnaire ascertainment of reported mouse exposure and dust
      sample mouse urinary protein allergen levels measured at age 2-3 months. RESULTS:
      Parental report of mouse exposure in the first year of life was associated with
      increased risk of transient wheeze and wheezing in early life. Current report of
      mouse exposure was also significantly associated with current wheeze throughout
      the first 7 years of life in the longitudinal analysis (P = 0.03 for overall
      relation of current mouse to current wheeze). However, early life mouse exposure
      did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to
      detectable levels of mouse urinary protein in house dust samples collected at age
      2-3 months was associated with a twofold increase in the odds of atopy
      (sensitization to >=1 allergen) at school age (95% confidence interval for odds
      ratio = 1.1-3.7; P = 0.03 in a multivariate analysis. CONCLUSIONS: Among children
      with parental history of asthma or allergies, current mouse exposure is
      associated with increased risk of wheeze during the first 7 years of life. Early
      mouse exposure was associated with early wheeze and atopy later in life.

PMID- 18616678
TI  - Targeted therapeutic approach for an anaplastic thyroid cancer in vitro and in
      vivo.
AB  - Anaplastic thyroid carcinoma (ATC) is among the most aggressive human
      malignancies, being responsible for the majority of thyroid cancer-related
      deaths. Despite multimodal therapy including surgery, chemotherapy, and
      radiotherapy, the outcome of ATC is poor. The human ATC cell line MB1, derived
      from tumor tissue of a 57-year-old man with thyroid cancer and pronounced
      neutrophilia, was established from surgically excised tumor tissue. The karyotype
      of the cell line shows many chromosomal abnormalities. Preclinical investigations
      have shown antitumor activity and effectiveness of the BRAF kinase inhibitor
      Sorafenib and the proteasome inhibitor Bortezomib. After establishment of the MB1
      cell line these agents were applied in vitro and, showing activity in a cell
      culture model, were also used for in vivo treatment. Sorafenib had some clinical
      effect, namely normalization of leucocytosis, but had no sustained impact on
      subsequent tumor growth and development of distant metastasis. Molecular
      diagnostics of the tumor demonstrated no BRAF mutations in exons 11 and 15
      concordant with a rather modest effect of Sorafenib on MB1 cell growth. Clinical
      benefit was seen with subsequent bortezomib therapy inducing a temporary halt to
      lymph node growth and a progression-free interval of 7 weeks. Our observations
      together with previous data from preclinical models could serve as a rationale
      for selecting those patients suffering from ATC most likely to benefit from
      targeted therapy. A prospective controlled randomized trial integrating kinase
      and proteasome inhibitors into a therapeutic regime for ATC is warranted.

PMID- 18616679
TI  - Significance of CXCR3 expression in gastric low-grade B-cell lymphoma of mucosa
      associated lymphoid tissue type for predicting responsiveness to Helicobacter
      pylori eradication.
AB  - Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct low-grade
      lymphoma that often regresses upon Helicobacter pylori eradication. It was
      reported that the chemokine receptor CXCR3 is expressed not only on activated T
      cells, but also on MALT lymphoma cells, and that CXCR3-positive B lymphocytes
      migrate or home to the MALT of MALT lymphoma. In the present study, we aimed to
      elucidate the correlation between CXCR3 expression and the clinicopathological
      features of gastric MALT lymphoma, and to determine whether CXCR3 expression was
      predictive of responsiveness to H. pylori eradication. Sixty-seven patients with
      gastric MALT lymphoma in a single-center study were treated with H. pylori
      eradication therapy. We evaluated the correlation of CXCR3 expression with
      response to H. pylori eradication therapy by logistic regression stratified
      according to potential confounders. Immunohistochemical analysis revealed that 28
      of 67 cases (42%) were positive for CXCR3 expression. CXCR3 expression was
      significantly more prevalent in those without H. pylori infection, advanced-stage
      disease, and in those with API2-MALT1 fusion. In overall analysis, those with
      CXCR3 expression showed a significantly increased risk of non-responsiveness to
      H. pylori eradication therapy (odds ratio = 28.6; 95% confidence interval 5.70
      143.4) compared to those without CXCR3 expression. This higher risk was observed
      consistently regardless of sex, API2-MALT1 fusion, H. pylori infection, or
      clinical stage. We showed that CXCR3 expression was an independent predictive
      factor for non-responsiveness to H. pylori eradication therapy in patients with
      gastric MALT lymphoma.

PMID- 18616680
TI  - TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine
      phosphorylation and its downstream signaling.
AB  - 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a key regulator of cell
      proliferation and survival signal transduction. PDK1 is known to be
      constitutively active and is further activated by Src-mediated phosphorylation at
      the tyrosine-9, -373, and -376 residues. To identify novel regulators of PDK1, we
      performed E. coli-based two-hybrid screening and revealed that tumor suppressor
      candidate 4 (TUSC4), also known as nitrogen permease regulator-like 2 (NPRL2),
      formed a complex with PDK1 and suppressed Src-dependent tyrosine phosphorylation
      and activation of PDK1 in vitro and in cells. The NH(2)-terminal 133 amino acid
      residues of TUSC4 were involved in binding to PDK1. The deletion mutant of TUSC4
      that lacked the NH(2)-terminal domain showed no inhibitory effects on PDK1
      tyrosine phosphorylation or activation. Thus, complex formation is indispensable
      for TUSC4-mediated PDK1 inactivation. The siRNA-mediated down-regulation of TUSC4
      induced cell proliferation, while ectopic TUSC4 expression inactivated the PDK1
      downstream signaling pathway, including Akt and p70 ribosomal protein S6 kinase,
      and increased cancer cell sensitivity to several anticancer drugs. Our results
      suggest that TUSC4/NPRL2, a novel PDK1-interacting protein, plays a role in
      regulating the Src/PDK1 signaling pathway and cell sensitivity to multiple cancer
      chemotherapeutic drugs.

PMID- 18616681
TI  - Epstein-Barr virus and gastric carcinoma: virus-host interactions leading to
      carcinoma.
AB  - Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) is a distinct subgroup
      of GC, comprising 10% of all cases of GC. EBV-associated carcinoma is the
      monoclonal growth of EBV-infected epithelial cells, and it represents a model of
      virus-host interactions leading to carcinoma. EBV-infected cells express several
      latent proteins (latency I program of viral latent gene expression) in EBV
      associated GC. However, latent membrane protein 2A (LMP2A) up-regulates the
      cellular survivin gene through the NFkB pathway, conferring resistance to
      apoptotic stimuli on the neoplastic cells. EBV-associated GC also shows
      characteristic abnormality, that is, global and non-random CpG island methylation
      of the promoter region of many cancer-related genes. Since the viral genes are
      also regulated by promoter methylation in the infected cells, the DNA methylation
      mechanism specific to EBV-associated GC may be an exaggeration of the cellular
      mechanism, which is primarily for defense against foreign DNA. Production of
      several immunomodulator molecules, inducing tumor-infiltrating lymphocyte and
      macrophages, serves to form the characteristic histologic pattern in EBV
      associated GC. The proposed sequence of events within the mucosa is as follows:
      EBV infection of certain gastric stem cells; expression of viral latent genes;
      abnormality of signal pathways caused by viral gene products; DNA methylation
      mediated repression of tumor suppressor genes; and monoclonal growth of EBV
      infected cells through interaction with other etiologic factors. Potentially
      useful therapeutic approaches to EBV-associated GC are those that utilize the
      virus-host interactions, such as bortezomib-induced and viral enzyme-targeted
      radiotherapy.

PMID- 18616682
TI  - beta-catenin is strongly elevated in rat colonic epithelium following short-term
      intermittent treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) and a high-fat diet.
AB  - Colon tumors expressing high levels of beta-catenin and c-myc have been reported
      in male F344 rats given three short cycles of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) alternating with a high-fat (HF) diet. Using
      the same experimental protocol, rats were euthanized 24 h after the last dose of
      PhIP so as to examine early changes in colonic crypt homeostasis and beta-catenin
      expression, before the onset of frank tumors. PhIP/HF dosing caused a significant
      increase in the bromodeoxyuridine labeling index throughout the entire colon, and
      within the colonic crypt column cleaved caspase-3 was elevated in the basal and
      central zones, but reduced in the luminal region. In vehicle/HF controls, beta
      catenin was immunolocalized primarily at the border between cells at the top of
      the crypt, whereas in rats given PhIP/HF diet there was strong cytoplasmic
      staining, which appeared as a gradient of increased beta-catenin extending from
      the base of the crypt column to the luminal region. Quantitative real-time PCR
      and immunoblot analyses confirmed that beta-catenin and c-myc were increased
      significantly in the colonic mucosa of rats given PhIP/HF diet. Collectively,
      these findings suggest that PhIP/HF cycling alters beta-catenin and c-myc
      expression in the colonic mucosa, resulting in expansion of the proliferative
      zone and redistribution of apoptotic cells from the lumen to the central and
      basal regions of the colonic crypt. Thus, during the early stages of colon
      carcinogenesis, alternating exposure to heterocyclic amines and a high-fat diet
      might facilitate molecular changes resulting in dysregulated beta-catenin and c
      myc expression.

PMID- 18616684
TI  - Long-term effect of deep brain stimulation for essential tremor on activities of
      daily living and health-related quality of life.
AB  - OBJECTIVES: To report long-term effects of thalamic deep brain stimulation (DBS)
      on activities of daily living (ADL) and health-related quality of life (HRQoL) in
      patients with essential tremor (ET). MATERIALS AND METHODS: Nineteen consecutive
      patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7
      years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy,
      Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and
      interview. RESULTS: There was a decrease of DBS efficacy on tremor between 1 and
      7 years post-operatively. The marked improvement in ADL at 1 year was no longer
      sustained at long-term, except for the ability to eat. Social life remained
      improved. CONCLUSION: Although there is a decrease of DBS effect on tremor at 7
      years, and even though further ageing and co-morbidities may impact on the well
      being of patients, there is still relevant benefit of DBS on few aspects of ADL
      and HRQoL in patients with ET.

PMID- 18616685
TI  - Purinergic activation of a leak potassium current in freshly dissociated myocytes
      from mouse thoracic aorta.
AB  - AIM: Exogenous ATP elicits a delayed calcium-independent K(+) current on freshly
      isolated mouse thoracic aorta myocytes. We investigated the receptor, the
      intracellular pathway and the nature of this current. METHODS: The patch-clamp
      technique was used to record ATP-elicited delayed K(+) current in freshly
      dissociated myocytes. RESULTS: ATP-elicited delayed K(+) current was not
      inhibited by a 'cocktail' of K(+) channel blockers (4-AP, TEA, apamin,
      charybdotoxin, glibenclamide). The amplitude of the delayed K(+) current
      decreased after the reduction of extracellular pH from 7.4 to 6.5. These two
      characteristics suggest that this current could be carried by the TASK subfamily
      of 'twin-pore potassium channels' (K2P). Purinergic agonists including dATP, but
      not ADP, activated the delayed K(+) current, indicating that P2Y(11) is the
      likely receptor involved in its activation. The PKC activator phorbol ester 12,13
      didecanoate stimulated this current. In addition, the PKC inhibitor Go 6850
      partially inhibited it. Real-time quantitative PCR showed that the genes encoding
      TASK-1 and TASK-2 are expressed. CONCLUSION: Our results indicate that blocker
      cocktail-insensitive delayed K(+) current in freshly dissociated aortic myocytes
      is probably carried by the TASK subfamily of twin-pore channels.

PMID- 18616686
TI  - One-per-occasion or less: are moderate-drinking postmenopausal women really
      healthier than their nondrinking and heavier-drinking peers?
AB  - BACKGROUND: While some reported benefits of moderate drinking are thought to be
      the direct results of physiological mechanisms associated with consumption, other
      effects may be attributable to mediating factors. Both explanations suggest that
      moderate drinkers may be healthier than nondrinking and heavier-drinking peers.
      The purpose of this study was to determine whether moderate-drinking
      postmenopausal women report healthier dietary and exercise patterns, and whether
      they demonstrate better physiological functioning compared with peers. This study
      also aimed to describe patterns of relationships between alcohol and measures of
      general health functioning in postmenopausal women. METHODS: One-hundred and
      fifteen women aged 50 to 65 participated. Participants completed alcohol
      interviews, diet and exercise questionnaires, and bone density examination. Blood
      pressure, height, and weight were assessed, and blood was collected to conduct
      basic chemistry and complete blood count tests. RESULTS: Postmenopausal moderate
      drinkers failed to demonstrate healthier dietary or exercise habits, and did not
      exhibit significantly better health-functioning compared with peers. They did
      evidence positive associations between drinking and healthy behavior, and between
      drinking and cardiovascular health. Relationships between alcohol and blood
      analytes differed between drinking groups, some of which suggested possible
      negative health consequences for higher-end drinkers in both drinking groups.
      CONCLUSIONS: These data suggested that moderate-drinking postmenopausal women are
      not significantly healthier than their non- or heavier-drinking peers, but may
      drink as part of a larger effort to take care of their health. Despite this, even
      1-drink-per-drinking-day moderate drinkers may have tendencies toward unhealthy
      conditions. Limitations include small sample size, inability to assess specific
      cardiac risk and socioeconomic status, small number of correlations, and clinical
      relevance of analyte values.

PMID- 18616688
TI  - Trazodone for sleep disturbance after alcohol detoxification: a double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Trazodone is a commonly prescribed off-label for sleep disturbance in
      alcohol-dependent patients, but its safety and efficacy for this indication is
      unknown. METHODS: We conducted a randomized, double-blind, placebo-control trial
      of low-dose trazodone (50 to 150 mg at bedtime) for 12 weeks among 173 alcohol
      detoxification patients who reported current sleep disturbance on a validated
      measure of sleep quality or during prior periods of abstinence. Primary outcomes
      were the proportion of days abstinent and drinks per drinking day over 6-months;
      sleep quality was also assessed. RESULTS: Urn randomization balanced baseline
      features among the 88 subjects who received trazodone and 85 who received
      placebo. The trazodone group experienced less improvement in the proportion of
      days abstinent during administration of study medication (mean change between
      baseline and 3 months: -0.12; 95% CI: -0.15 to -0.09), and an increase in the
      number of drinks per drinking day on cessation of the study medication (mean
      change between baseline and 6 months, 4.6; 95% CI: 2.1 to 7.1). Trazodone was
      associated with improved sleep quality during its administration (mean change on
      the Pittsburgh Sleep Quality Index between baseline and 3 months: -3.02; 95% CI: 
      3.38 to -2.67), but after it was stopped sleep quality equalized with placebo.
      CONCLUSIONS: Trazodone, despite a short-term benefit on sleep quality, might
      impede improvements in alcohol consumption in the postdetoxification period and
      lead to increased drinking when stopped. Until further studies have established
      benefits and safety, routine initiation of trazodone for sleep disturbance cannot
      be recommended with confidence during the period after detoxification from
      alcoholism.

PMID- 18616687
TI  - Relationship between medication adherence and treatment outcomes: the COMBINE
      study.
AB  - BACKGROUND: Within the alcoholism field, there is mounting evidence supporting an
      important relationship between medication adherence and drinking outcomes. Little
      is known however, about the complex relationships between medication and
      treatment variables and drinking outcomes. The present paper reports on the
      differential impact of medication adherence and treatment factors on drinking
      outcomes. Data derived from the COMBINE Study was used to investigate the
      interrelationships between medication adherence, combination treatments and
      drinking outcomes. METHODS: Twelve hundred and twenty-six patients were
      randomized to 1 of 8 different combination treatments involving 2 medications-
      naltrexone and acamprosate and placebo, and 2 behavioral treatments--medical
      management (MM) and combined behavioral intervention (CBI). Two primary drinking
      outcomes were percent days abstinent (PDA) and time to first heavy drinking day.
      Medication adherence was defined as a proportion that reflects the number of
      pills taken by the maximum number of pills expected to be taken over the course
      of the trial. A generalized linear mixed model was used to estimate the effects
      of adherence on PDA while proportional hazards model was used to examine similar
      co-variate effects on time to first heavy drinking day. RESULTS: Concerning time
      to first heavy drinking day, a significant three-way interaction was found
      between medication adherence, CBI and naltrexone (p = 0.0160). Within the MM only
      plus placebo group (no CBI), significant differences were found in "recovery"
      (i.e., no heavy drinking days) rates between adherers and nonadherers (40% vs.
      10%, p < 0.0001). Such differences became nonsignificant (p = 0.12) when CBI was
      introduced into the relationship. CBI did not add any such advantage to
      naltrexone-treated patients. CONCLUSIONS: CBI might serve a protective function
      for nonadherers in the placebo group; the median relapse time was reduced when
      these nonadherers were exposed to the alcohol specialty intervention. CBI offered
      little additional benefit to nonadherers in the naltrexone group. Among
      nonadherers in the naltrexone group, relapse rates appear to be more a function
      of inadequate exposure to the active medication and less influenced by CBI.

PMID- 18616689
TI  - Hazardous drinking: prevalence and associations in the Finnish general
      population.
AB  - BACKGROUND: Hazardous drinking, defined as consuming alcohol on a risky level and
      not meeting the diagnostic criteria of alcohol use disorders (AUDs), has been
      suggested for a new complementary nondependence diagnosis. This study aimed to
      investigate the prevalence and associations of hazardous drinking in comparison
      to AUDs, moderate drinking, and abstinence. METHODS: A national representative
      sample of Finns was examined in the Health 2000 Survey. For 4477 subjects aged 30
      to 64 years (76%, 2341 females), both the quantity frequency data about alcohol
      consumption and Composite International Diagnostic Interview (CIDI) data
      concerning AUD diagnoses were available. The nationally recommended limits for
      hazardous dinking were used (males: 24 drinks, females: 16 drinks/wk). Logistic
      regression models were used to analyze associations. RESULTS: The prevalence of
      hazardous drinking was 5.8%. Hazardous drinking was more prevalent among males
      than females (8.5% vs. 3.1%). It was most prevalent among the subjects aged 40 to
      49 years (7.3%), divorced or separated (8.3%), unemployed (8.2%) and subjects
      living in the southern (Helsinki) region (7.5%). AUDs versus hazardous drinking
      were more likely to be in males versus females and in the unemployed versus
      employed. Subjects aged 40 and over had higher odds for hazardous drinking versus
      AUDs. The odds for hazardous versus moderate drinking were higher for males
      versus females (adjusted odds ratio = 3.24), for subjects aged over 40 years,
      unemployed versus employed and cohabiting, divorced/separated or unmarried
      subjects versus married subjects. CONCLUSION: The high prevalence of hazardous
      drinking makes it an important public health concern. Hazardous drinkers have
      different sociodemographic characteristics as compared to people in other alcohol
      use categories.

PMID- 18616691
TI  - A review of adherence to drug therapy in patients with overactive bladder.
AB  - Drug therapy for overactive bladder (OAB) is associated with improvements in
      symptoms and quality of life, but the short- and long-term adherence and
      persistence is suboptimal. In this review we outline methods of measuring, and
      factors affecting, adherence to pharmacotherapy in patients with OAB. Clinical
      practice suggests that adherence rates reported in clinical trials are much
      greater than in real practice. Factors affecting adherence include psychological
      and social variables that might alter patients' perception of the benefits of
      taking medication, and the effect of comorbidity and polypharmacy. Whilst there
      is some evidence that lack of efficacy and side-effects are contributory, these
      additional factors are also important.

PMID- 18616692
TI  - The two homologous chaperonin 60 proteins of Mycobacterium tuberculosis have
      distinct effects on monocyte differentiation into osteoclasts.
AB  - Mycobacterium tuberculosis produces two homologous chaperonin (Cpn)60 proteins,
      Cpn60.1 and Cpn60.2 (Hsp65). Both proteins stimulate human and murine monocyte
      cytokine synthesis but, unlike Cpn60 proteins from other microbial species, fail
      to stimulate the breakdown of cultured murine bone. Here, we have examined the
      mechanism of action of these proteins on bone remodelling and osteoclastogenesis,
      induced in vitro in murine calvarial explants and the murine monocyte cell line
      RAW264.7. Additionally, we have determined their effect on bone remodelling in
      vivo in an animal model of arthritis. Recombinant Cpn60.1 but not Cpn60.2
      inhibited bone breakdown both in vitro, in murine calvaria and in vivo, in
      experimental arthritis. Analysis of the mechanism of action of Cpn60.1 suggests
      that this protein works by directly blocking the synthesis of the key osteoclast
      transcription factor, nuclear factor of activated T cells c1. The detection of
      circulating immunoreactive intact Cpn60.1 in a small number of patients with
      tuberculosis but not in healthy controls further suggests that the skeleton may
      be affected in patients with tuberculosis. Taken together, these findings reveal
      that M. tuberculosis Cpn60.1 is a potent and novel inhibitor of
      osteoclastogenesis both in vitro and in vivo and a potential cure for bone
      resorptive diseases like osteoporosis.

PMID- 18616693
TI  - Intracellular microbes and haemophagocytosis.
AB  - Haemophagocytosis (hemophagocytosis) is the phenomenon of activated macrophage
      consumption of red and white blood cells, including professional phagocytes and
      lymphocytes. It can occur in patients with severe cases of intracellular
      microbial infection, including avian influenza, leishmaniasis, tuberculosis and
      typhoid fever. While well-known to physicians since at least the mid-1800s,
      haemophagocytosis has been little studied due to a paucity of tractable animal
      and cell culture models. Recently, haemophagocytosis has been described in a
      mouse model of typhoid fever, and it was noted that the infectious agent,
      Salmonella enterica, resides within haemophagocytic macrophages in mice. In
      addition, a cell culture model for haemophagocytosis revealed that S. enterica
      preferentially replicate in haemophagocytic macrophages. This review describes
      how, at the molecular and cellular levels, S. enterica may promote and take
      advantage of haemophagocytosis to establish long-term systemic infections in
      mammals. The role, relevance and possible molecular mechanisms of
      haemophagocytosis are discussed within the context of other microbial infections
      and of genetic deficiencies in which haemophagocytosis occurs and is associated
      with morbidity.

PMID- 18616694
TI  - Haematopoietic lineage-committed bone marrow cells,  but not cloned cultured
      mesenchymal stem cells, contribute to  regeneration of renal tubular epithelium
      after HgCl  2  -induced  acute tubular injury.
AB  - OBJECTIVE: Our previous studies have demonstrated that endogenous bone arrow
      cells (BMCs) contribute to renal tubular regeneration after acute tubular injury.
      The aim of this study was to examine which fraction of BMCs, haematopoietic
      lineage marrow cells (HLMCs) or mesenchymal stem cells (MSCs), are effective.
      MATERIALS AND METHODS: Six-week-old female mice were lethally irradiated and were
      transplanted with female enhanced green fluorescent protein-positive (GFP(+)),
      plastic on-adherent marrow cells (as a source of HLMCs) plus cloned cultured male
      GFP(-) MSCs. Four weeks later, they were assigned into two groups: control mice
      with vehicle treatment and mice treated with HgCl2. Tritiated thymidine was given
      1 h before animal killing which occurred at intervals over 2 weeks. Kidney
      sections were stained for a tubular epithelial marker, cell origin indicated by
      GFP immunohistochemistry or Y chromosome in situ hybridization; periodic acid
      Schiff staining was performed, and samples were subjected to autoradiography. One
      thousand consecutive renal tubular epithelial cells per mouse, in S phase, were
      scored as either female (indigenous) GFP+(HLMC-derived) or male (MSC-derived).
      RESULTS: Haematopoietic lineage marrow cells and MSCs stably engrafted into bone
      marrow and spleen, but only HLMC-derived cells, not MSCs, were found in the renal
      tubules and were able to undergo DNA synthesis after acute renal injury. A few
      MSCs were detected in the renal interstitium, but their importance needs to be
      further explored. CONCLUSION: Haematopoietic lineage marrow cells, but not cloned
      cultured MSCs, can play a role not only in normal wear-and-tear turnover of renal
      tubular cells, but also in repair after tubular injury.

PMID- 18616696
TI  - Proteomic analysis of human bone marrow mesenchymal stem cells transduced with
      human telomerase reverse transcriptase gene during proliferation.
AB  - OBJECTIVES: Previous studies have reported immortalization and tumorigenicity of
      human mesenchymal stem cells (hMSCs) transduced with exogenous human telomerase
      reverse transcriptase (hTERT). We also have established a line of hMSCs
      transduced with hTERT (hTERT-hMSCs) and we have cultured these cells for 290
      population doublings (PDs) during which they demonstrated a large proliferation
      potential but with no tumorigenicity. The aim of this study was to investigate
      the protein expression profile of hTERT-hMSCs with two-dimensional gel
      electrophoresis and peptide mass fingerprinting by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, to be able to analyse the
      effects of exogenous hTERT on protein expression in hMSCs. MATERIALS AND METHODS:
      We generated proteome maps of primary hMSCs and hTERT-hMSCs at PD 95 and PD 275.
      RESULTS: A total of 1543 +/- 145 protein spots in gels of primary MSCs at PD 12,
      1611 +/- 186 protein spots in gels of hTERT-hMSCs at PD 95 and 1451 +/- 126
      protein spots in gels of hTERT-hMSCs at 275 PD were detected. One hundred of
      these were successfully identified, including 20 which were differentially
      expressed. CONCLUSIONS: The results suggest that sustaining levels of prohibitin
      and p53 expression along with differential expression of proteins in hTERT-hMSCs
      provide an insight into lack of transforming activity of hTERT-hMSCs during cell
      proliferation.

PMID- 18616695
TI  - Phospholipase C-delta extends intercellular signalling range and responses to
      injury-released growth factors in non-excitable cells.
AB  - OBJECTIVES: Intercellular communication in non-excitable cells is restricted to a
      limited range close to the signal source. Here, we have examined whether
      modification of the intracellular microenvironment could prolong the spatial
      proposition of signal generation and could increase cell proliferation. MATERIAL
      AND METHODS: Mathematical models and experimental studies of endothelial repair
      after controlled mechanical injury were used. The models predict the diffusion
      range of injury-released growth factors and identify important parameters
      involved in a signalling regenerative mode. Transfected human umbilical vein
      endothelial cells (HUVECs) were used to validate model results, by examining
      intercellular calcium signalling range, cell proliferation and wound healing
      rate. RESULTS: The models predict that growth factors have a limited capacity of
      extracellular diffusion and that intercellular signals are specially sensitive to
      cell phospholipase C-delta (PLCdelta) levels. As basal PLCdelta levels are
      increased by transfection, a significantly increased intercellular calcium range,
      enhanced cell proliferation, and faster wound healing rate were observed.
      CONCLUSION: Our in silico and in vitro studies demonstrated that non-excitable
      endothelial cells respond to stimuli in a complex manner, in which intercellular
      communication is controlled by physicochemical properties of the stimulus and by
      the cell microenvironment. Such findings may have profound implications for our
      understanding of the tight nature of autocrine cell growth control, compensation
      to stress states and response to altered microenvironment, under pathological
      conditions.

PMID- 18616697
TI  - Identification of osteo-adipo progenitor cells in fat tissue.
AB  - OBJECTIVES: In this study, a group of cells that expressed both osteogenic and
      adipogenic characters was identified from murine adipose stromal cells. MATERIALS
      AND METHODS: These cells could be enriched in the Sca-1-1 population and express
      both osteogenic and adipogenic genes. Osteogenic induction enhanced expression of
      osteogenic genes and inhibited expression of adipogenic genes, while adipogenic
      induction enhanced expression of adipogenic genes and inhibited expression of
      osteogenic genes. These cells have been called osteo-adipo progenitors (OAPs).
      RESULTS: OAPs expressed transcription factor runt-related transcription factor 2
      (RUNX2) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      proteins in cytoplasm. When OAPs were cultured in adipogenic medium, PPAR-gamma
      moved to the nucleus and the cells differentiated into adipocytes, while the
      RUNX2 remained in the cytoplasm. In contrast, when OAPs were cultured in
      osteogenic medium, RUNX2 moved to the nucleus and the cells differentiated to
      osteocytes, while the PPAR-gamma remained in the cytoplasm. CONCLUSIONS: These
      experiments suggest that osteoblasts and adipocytes share a common predecessor,
      the OAP, in murine adipose stromal cells.

PMID- 18616698
TI  - An efficient experimental strategy for mouse embryonic stem cell differentiation
      and separation of a cytokeratin-19-positive population of insulin-producing
      cells.
AB  - OBJECTIVES: Embryonic stem cells are a potential source for insulin-producing
      cells, but existing differentiation protocols are of limited efficiency. Here,
      the aim has been to develop a new one, which drives development of embryonic stem
      cells towards insulin-producing cells rather than to neuronal cell types, and to
      combine this with a strategy for their separation from insulin-negative cells.
      MATERIALS AND METHODS: The cytokeratin-19 (CK19) promoter was used to control the
      expression of enhanced yellow fluorescence protein in mouse embryonic stem cells
      during their differentiation towards insulin-producing cells, using a new
      optimized four-stage protocol. Two cell populations, CK19(+) and CK19(-) cells,
      were successfully fluorescence sorted and analysed. RESULTS: The new method
      reduced neuronal progeny and suppressed differentiation into glucagon- and
      somatostatin-producing cells. Concomitantly, beta-cell like characteristics of
      insulin-producing cells were strengthened, as documented by high gene expression
      of the Glut2 glucose transporter and the transcription factor Pdx1. This novel
      protocol was combined with a cell-sorting technique. Through the combined
      procedure, a fraction of glucose-responsive insulin-secreting CK19(+) cells was
      obtained with 40-fold higher insulin gene expression and 50-fold higher insulin
      content than CK19(-) cells. CK19(+) cells were immunoreactive for C-peptide and
      had ultrastructural characteristics of an insulin-secretory cell. CONCLUSION:
      Differentiated CK19(+) cells reflect an endocrine precursor cell type of ductal
      origin, potentially suitable for insulin replacement therapy in diabetes.

PMID- 18616699
TI  - Effect of separase depletion on ionizing radiation-induced cell cycle checkpoints
      and survival in human lung cancer cell lines.
AB  - OBJECTIVES: This study is to evaluate the effect of separase depletion on cell
      cycle progression of irradiated and non-irradiated cells through the G(2)/M
      phases and consecutive cell survival. MATERIALS AND METHODS: Separase was
      depleted with siRNA in two human non-small cell lung carcinoma (NSCLC) cell
      lines. Cell cycle progression, mitotic fraction, DNA repair, apoptotic and
      clonogenic cell death were determined. RESULTS: By depletion of endogenous
      separase with siRNA in NSCLCs, we showed that separase affects progression
      through the G(2) phase. In non-irradiated exponentially growing cells, separase
      depletion led to an increased G(2) accumulation from 17.2% to 29.1% in H460 and
      from 15.7% to 30.9% in A549 cells and a decrease in mitotic cells. Depletion of
      separase significantly (P < 0.01) increased the fraction of radiation-induced
      G(2) arrested cells 30-56 h after irradiation and led to decrease in the mitotic
      fraction. This was associated with increased double-strand break repair as
      measured by gamma-H2AX foci kinetics in H460 cells and to a lesser extent in A549
      cells. In addition, a decrease in the expression of mitotic linked cell death
      after irradiation was found. CONCLUSIONS: These results indicate that separase
      has additional targets involved in regulation of G(2) to M progression after DNA
      damage. Prolonged G(2) phase arrest in the absence of separase has consequences
      on repair of damaged DNA and cell death.

PMID- 18616700
TI  - Interleukin-10-592C/A, -819C/T and -1082A/G promoter variants affect the
      susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients.
AB  - BACKGROUND: The Interleukin (IL)-10 polymorphic variants -1082G/A, -819C/T and 
      592C/A were linked with obesity, metabolic syndrome, and type 2 diabetes (T2DM).
      We investigated the hypothesis that IL-10 promoter polymorphisms may be
      associated with the progression of diabetic nephropathy (DN). DESIGN: Case
      controlled study. PATIENTS: Study subjects comprised of 515 DN patients, and 402
      normoalbuminuric (DWN) T2DM patients. MEASUREMENTS: IL-10 genotyping was done by
      PCR-based assays, and the contributions of the IL-10 polymorphic variants to DN
      were analysed by haplotype analysis and multivariate regression analysis.
      RESULTS: Decreased prevalence of (mutant) -819T allele and -819C/T genotype was
      seen in DN patients; neither the -1082G/A nor the -592C/A polymorphism was
      associated with DN. Three-loci haplotype (-1082GA/-819CT/-592CA) analysis
      identified GTC as DN-protective haplotype. Multivariate regression analysis
      confirmed the association of GTC haplotype (P = 0.045; OR = 0.56, 95% CI: 0.31
      0.99), and in addition identified GTA haplotype (P = 0.044; OR = 0.54, 95% CI:
      0.30-0.98) as independent predictors of DN after controlling for a number of
      covariates (age, sex, BMI; hypertension, glucose, HbA1c, DN duration, total
      cholesterol, medications). CONCLUSION: This study suggests that IL-10 promoter
      polymorphism influence the risk of nephropathy in Tunisian T2DM patients.

PMID- 18616701
TI  - Variant rs9939609 in the FTO gene is associated with obesity in an adult
      population from Spain.
AB  - OBJECTIVE: Recently independent studies, including genome-wide scans, have shown
      that variation in the fat mass and obesity associated gene (FTO) were
      significantly associated with obesity in populations of European origin. DESIGN
      AND METHODS: In this study we examined the association between rs9939609 FTO
      variant and obesity related parameters in a population based-study of 732
      unrelated individuals (46.9% males and 53.1% females; ages 35-74 years) from the
      province of Segovia in Central Spain (Castille). RESULTS: The AA genotype was
      significantly more frequent in obese individuals (defined as body mass index >or=
      30 kg/m(2), n = 207; 80 males and 127 females) than in non-obese (19.9%vs. 13.7%,
      P = 0.026). In addition to increased obesity, AA homozygous individuals had
      higher waist circumference than individuals with AT heterozygous and TT
      homozygous genotypes. The minor A-allele of rs9939609 was associated with an
      increased odds ratio (OR) for obesity [OR 1.51, 95% confidence interval (CI) 1.10
      2.12] as compared to the TT genotype. This difference was also statistically
      significant even after the adjustment for sex and age (OR 1.46, 95% CI 1.02
      2.07). CONCLUSIONS: Our results support the association of FTO gene variants with
      obesity, including parameters of visceral (abdominal) obesity, in an adult
      general population from Spain. Overall we confirm the previously reported
      association studies between variants in FTO gene and the risk of obesity.

PMID- 18616702
TI  - Repeated transsphenoidal pituitary surgery (TS) via the    endoscopic technique:
      a good therapeutic option for recurrent    or persistent Cushing's disease (CD).
AB  - BACKGROUND: No data on results of repeated transsphenoidal surgery via the
      endoscopic technique for patients with persistent or recurrent Cushing's disease
      are available. DESIGN AND PATIENTS: We retrospectively evaluated the remission
      rates and complications of repeated transsphenoidal surgery via the endoscopic
      technique in 14 patients with persistent (N = 6) or recurrent (N = 8) Cushing's
      disease treated in our centre between 1999 and 2007. MAIN OUTCOMES: Remission was
      defined as the disappearance of symptoms of hypercortisolism with basal plasma
      cortisol level < or = 50 nmol/l 24-48 h after glucocorticoid withdrawal and/or
      suppression of plasma cortisol level < or = 50 nmol/l after 1 mg dexamethasone
      overnight within the first 3 months after transsphenoidal surgery. RESULTS: With
      repeated endoscopic transsphenoidal surgery a remission rate of 10/14 (71%) was
      achieved. No patient had a relapse during a median follow-up of 24 months.
      Cerebrospinal fluid leakage was the most frequent complication (6 patients) and
      11 patients required hormonal substitution after surgery. The success of repeated
      transsphenoidal surgery could not be predicted by visualization of an adenoma on
      MRI before first or second surgery, histopathological confirmation of an ACTH
      secreting adenoma after first or second surgery, treatment with cortisol lowering
      agents before first or second surgery, the operation technique used during the
      first surgery, persistent vs. recurrent disease after the first surgery, age,
      gender and interval between the two surgeries. CONCLUSION: Repeated
      transsphenoidal surgery via the endoscopic technique is a good treatment option
      for selected patients with recurrent or persistent Cushing's disease following
      primary pituitary surgery.

PMID- 18616703
TI  - Detection of enterovirus RNA in postoperative thyroid tissue specimens.
AB  - CONTEXT: Autoimmune thyroiditis is a very common disease. A genetic
      predisposition and environmental factors such as viruses are thought to
      contribute to the development of autoimmune thyroiditis. Enteroviruses, which are
      involved in other autoimmune diseases, are attractive candidates. OBJECTIVE: To
      investigate the presence of enteroviral genome sequences in postoperative thyroid
      tissues with lymphocytic infiltration, a common histological feature of
      thyroiditis. SUBJECTS AND METHODS: Postoperative thyroid specimens collected
      prospectively from 86 patients were blindly frozen at -80 degrees C. The presence
      of EV genome sequences in the samples was blindly investigated by real-time RT
      PCR. Clinical data, histological findings and levels of anti-TPO antibodies were
      collected. RESULTS: EV-RNA detection was positive (up to 36 cycles) or weakly
      positive (37-39 cycles) in 22 out of 86 patients (25%). EV-RNA (positive or
      weakly positive signal) was detected in 5 out of 27 (18.5%) thyroid specimens
      with lymphocytic infiltration, and in 17 out of 59 (29%) thyroid specimens
      without lymphocytic infiltration (P = 0.4). No correlation was observed between
      EV-RNA detection in thyroid and the presence of anti-TPOAb. EV-RNA was detected
      in 3 out of 11 patients histologically diagnosed as thyroiditis (27.3%) and in 18
      out of 74 patients (24.3%) with thyroid tumours (multinodular goitre, adenoma and
      carcinoma) (P = 0.5) and in one patient with a normal thyroid. CONCLUSION: EV-RNA
      can be detected in thyroid tissue from patients with various thyroid diseases,
      but there is no relationship between the presence of EV-RNA and thyroiditis.
      Further studies are needed to clarify the role of EV in thyroid diseases.

PMID- 18616704
TI  - Colostrum iodine and perchlorate concentrations in Boston-area women: a cross
      sectional study.
AB  - OBJECTIVE: To measure levels of colostrum iodine, which has not been previously
      measured, and perchlorate and cotinine (a surrogate for thiocyanate derived from
      cigarette smoke) in women up to 60 h postpartum. Perchlorate and thiocyanate are
      environmental inhibitors of iodide transport into the thyroid and lactating
      breast. DESIGN: Cross-sectional. PATIENTS: Ninety seven postpartum women in
      Boston, Massachusetts, USA. MEASUREMENTS: Colostrum iodine and perchlorate, and
      spot urine iodine, perchlorate, cotinine and creatinine concentrations were
      measured. RESULTS: Sufficient colostrum was obtained to measure iodine in 61
      samples and perchlorate in 46 samples. Median colostrum iodine content was 51.4
      micromol/l (range 21.3-304.2 microg/l). Perchlorate was detectable in 43 of 46
      colostrum samples (median 2.5 micromol/l; range, < 0.05-188.9 micromol/l). Median
      urine iodine in 97 samples was 82.2 micromol/l (range, 10.3-417.1 micromol/l).
      Perchlorate was detectable in all 97 urine samples (median 2.6 micromol/l; range,
      0.2-160.6 micromol/l). Colostrum iodine content was not significantly correlated
      with levels of colostrum perchlorate or concentrations per litre of urinary
      iodine, perchlorate, or cotinine. Colostrum perchlorate concentrations were not
      significantly associated with urinary iodine, perchlorate, or cotinine levels.
      Urinary cotinine levels were not significantly associated with urinary iodine or
      perchlorate levels. There was no association between maternal urinary iodine and
      urinary perchlorate levels. CONCLUSIONS: Iodine is present in human colostrum and
      thus available for breastfeeding infants immediately after birth. Perchlorate was
      also present in 93% of samples measured, but the concentrations did not correlate
      with colostrum iodine concentrations.

PMID- 18616705
TI  - Polycystic ovary syndrome (PCOS) trilogy: a translational and clinical review.

PMID- 18616706
TI  - Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of
      Italian patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal
      dystrophy (APECED) and in their relatives.
AB  - OBJECTIVE: Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy
      (APECED) is a rare syndrome characterized by chronic candidiasis, chronic
      hypoparathyroidism and Addison's disease. APECED has been associated with
      mutations in autoimmune regulator (AIRE) gene. Our aim is to perform a genetic
      analysis of the AIRE gene in Italian APECED patients and in their relatives.
      Design AIRE mutations were determined by DNA sequencing in all subjects. Patients
      were tested for clinical autoimmune or non-autoimmune diseases, or for organ and
      non-organ specific autoantibodies. PATIENTS: A total of 24 Italian patients with
      APECED (15 from the Venetian region, 2 from Southern-Tyrol, 4 from Apulia, 3 from
      Sicily), 25 relatives and 116 controls were studied. RESULTS: Ten out of the 15
      Venetian patients (66%) were homozygous for R257X or compound heterozygous with
      1094-1106del13. One patient was homozygous for 1094-1106del13 and another for
      R139X. A novel mutation (1032-1033delGT) in combination with 1094-1106del13 was
      identified in one patient. No mutations were found in two cases. Two patients
      from Southern Tyrol were homozygous for R257X and for 1094-1106del13bp. All
      patients from Apulia were homozygous or heterozygous for W78R combined with
      Q358X. The patients from Sicily were homozygous for R203X or compound
      heterozygous with R257X. The analysis of the genotype-phenotype revealed that
      patients carrying 1094-1106del13 at the onset of Addison's disease were
      significantly older than those carrying other mutations. The genetic study of 25
      relatives identified 20 heterozygous subjects. They suffered from various
      autoimmune and non-autoimmune diseases but no major disease of APECED was found.
      CONCLUSION: These data demonstrate the great genetic heterogeneity for the AIRE
      mutations in Italian APECED patients, and that the heterozygosity for AIRE
      mutations do not produce APECED.

PMID- 18616707
TI  - Well-differentiated endocrine pancreatic tumour and Wernicke's encephalopathy.

PMID- 18616708
TI  - Effects of aromatase inhibition in hypogonadal older men: a randomized, double
      blind, placebo-controlled trial.
AB  - OBJECTIVE: To assess the effects of sustained aromatase inhibition in older
      hypogonadal men. DESIGN AND PATIENTS: In a 1-year randomized, double-blind,
      placebo-controlled trial, 88 men, aged 60 and older with testosterone levels
      between 5.2 and 10.4 nmol/L on a single measure or between 10.4 and 12.1 nmol/L
      on two consecutive measures, and symptoms of hypogonadism were recruited.
      Subjects received either anastrozole 1 mg daily or placebo. MEASUREMENTS: Changes
      in gonadal steroid hormone levels, body composition (by computerized tomography
      (CT) and dual x-ray absorptiometry (DXA)), strength, prostate specific antigen
      (PSA), symptoms of benign prostatic hypertrophy (BPH), hematocrit and lipid
      levels were assessed. RESULTS: Testosterone levels increased from 11.2 +/- 3.3
      nmol/L at baseline to 18.2 +/- 4.8 nmol/L at month 3 (p < 0.0001 vs. placebo)
      while bioavailable testosterone levels increased from 2.7 +/- 0.8 nmol/L at
      baseline to 5.4 +/- 1.7 nmol/L at month 3 (p < 0.0001 vs. placebo). Testosterone
      and biotestosterone levels peaked at month 3 and then declined by month 12
      (though they remained significantly higher than baseline and greater than
      placebo). Estradiol levels decreased from 55.8 +/- 15.4 pmol/L at baseline to
      42.2 +/- 13.6 pmol/L at month 3 and then remained stable (p < 0.0001). Body
      composition and strength did not change, nor did PSA, BPH symptoms, hematocrit or
      lipid levels. CONCLUSIONS: Anastrozole administration normalized androgen
      production in older hypogonadal men and decreased estradiol production modestly.
      These alterations did not improve body composition or strength.

PMID- 18616710
TI  - Measurement of testosterone in the diagnosis of hypogonadism in the ageing male.

PMID- 18616711
TI  - Multiple endocrine neoplasia type 1 (MEN1): its manifestations and effect of
      genetic screening on clinical outcome.
AB  - OBJECTIVE: Effect of genetic screening on outcome in multiple endocrine neoplasia
      type 1 (MEN1) remains unclear. Expression of MEN1 is described using currently
      available diagnostic techniques. Manifestations and outcome are compared in
      patients diagnosed because of clinical expression with those diagnosed by genetic
      screening. DESIGN: Retrospective cohort study. Patients are divided into two
      groups: patients with a (i) clinical MEN1 diagnosis and (ii) MEN1 diagnosis by
      genetic screening. PATIENTS AND MEASUREMENTS: Demographic and clinical data were
      collected on MEN1 patients treated in the UMCU up to 1 January 2008. Results of
      mutation analysis were obtained from the Department of Medical Genetics. RESULTS:
      A total of 74 patients was included (median follow-up 5.5 year); 78% had
      hyperparathyroidism, 46% a pancreatic neuro-endocrine tumour (NET), 38% a
      pituitary abnormality, 8% a NET of other origin and 16% an adrenal adenoma at the
      end of follow-up. Of the patients 18% had no manifestation. All five MEN1-related
      tumours were seen as first manifestation. Compared with patients identified by
      genetic screening, patients with a clinical MEN1 diagnosis had significantly more
      manifestations at diagnosis (P < 0.001) and at end of follow-up (P = 0.002).
      Eleven of 30 patients with a genetic MEN1 diagnosis (mean age at diagnosis 30.0
      years) already had manifestations at diagnosis. No malignancy or death was seen
      in genetically diagnosed patients. CONCLUSIONS: MEN1 is a syndrome with high
      morbidity. Genetic diagnosis is associated with less morbidity at diagnosis and
      at follow-up. Early genetic diagnosis might therefore lead to improvement of long
      term outcome.

PMID- 18616713
TI  - Spinal volumetric trabecular bone mass in acromegalic patients: a longitudinal
      study.
AB  - OBJECTIVE: Data on trabecular bone mass in acromegaly are controversial. All the
      studies are cross-sectional and bone mineral density (BMD) has been evaluated
      largely by dual X-ray absorptiometry (DXA), which is influenced by bone
      enlargement. In this study we assessed in acromegalic patients the effects
      overtime of GH excess on trabecular bone mass measured by single-energy
      quantitative computed tomography (QCT) which is not influenced by bone size.
      DESIGN: Longitudinal retrospective study. PATIENTS: A total of 46 acromegalic
      patients followed-up for 48 months (median), subdivided into four groups: group A
      (eugonadal patients with active disease: n = 13), group B (hypogonadal patients
      with active disease; n = 9), group C (eugonadal patients with controlled disease;
      n = 10), group D (hypogonadal patients with controlled disease; n = 14).
      MEASUREMENTS: Serum GH and IGF-I levels, spinal trabecular BMD, and vertebral
      fractures were evaluated in all patients. BMD variations were reported as change
      (Delta) in Z-values (Z-QCT) measured at baseline and end of follow-up per year
      (Delta Z-QCT). RESULTS: Delta Z-QCT was greater in group A vs. group B and D (P
      =0.002 and P = 0.0001, respectively) and in group C vs. group D (P =0.009).
      Multivariate regression analysis showed that hypogonadal status (beta = -0.69; P
      = 0.001) and baseline duration of hypogonadism (beta = 0.44; P = 0.02) but not
      baseline duration of acromegaly, length of follow-up and disease activity, were
      significantly associated with Delta Z-QCT. CONCLUSIONS: This longitudinal study
      suggests that the effect of chronic GH excess on spinal trabecular bone mass
      seems to be anabolic in active eugonadal patients but not in hypogonadal ones.

PMID- 18616714
TI  - Ghrelin and the differential regulation of des-acyl (DSG) and oct-anoyl ghrelin
      (OTG) in human adipose tissue (AT).
AB  - OBJECTIVES: Ghrelin, an important central acting orexigenic hormone, is
      predominantly secreted in the gastrointestinal tract. However little is known
      about the action of ghrelin in human adipose tissue (AT). AIM: To study the
      expression of ghrelin in AT, the effects of octanoyl-(OTG) and des-acyl (DSG)
      ghrelin on lipolysis and lipogenesis, leptin release and potential peripheral
      signalling through the Y1 receptor. METHODS: Ex vivo human AT was obtained from
      women undergoing elective surgery (46 (mean +/- SD) 6.8 years, body mass index
      (BMI): 25.6 +/- 5.0 kg/m(2), n = 20). Abdominal-subcutaneous (AbdSc) adipocytes
      were isolated and treated with recombinant human (rh) OTG and DSG to assess lipid
      metabolism leptin release and the influence of Y1-receptor blocker. RESULTS:
      Ghrelin was expressed in AbdScAT and negatively correlated with BMI (lean: 3.6 +/
      0.74 optical-density-units (OD), obese: 1.64 +/- 0.45 OD, *P < 0.05). Only DSG
      significantly suppressed glycerol release (Control (C): 286 +/- 58 microl/l; DSG
      1 nm: 224 +/- 38 microl/l downward arrow*; DSG 100 nm: 172 +/- 13 microl/l
      downward arrow*,* downward arrow P < 0.05, n = 7) and reduced hormone sensitive
      lipase expression (C: 1.0 +/- 0.3 OD; DSG 1 nm: 0.8 +/- 0.3 OD downward arrow*;
      DSG 100 nm: 0.6 +/- 0.1 OD downward arrow*, n = 4). However, both isoforms
      increased lipoprotein lipase expression (C: 1.0 +/- 0.3OD; DSG 100 nm: 0.2 +/-
      0.4 OD upward arrow*; OTG 100 nm: 2.5 +/- 0.3 OD upward arrow*, n = 4), whilst
      blockade of Y1 eliminated this effect in both. Leptin was down-regulated by DSG
      only (DSG 1 nm: 5.3 +/- 0.7 ng/ml; DSG 100 nm: 4.1 +/- 0.7 ng/ml*) and was
      significant after BMI adjustment (P = 0.029). CONCLUSION: Ghrelin was expressed
      in human AbdSc AT. In vitro, both OGT and DSG appear to mediate fat deposition
      with the lipogenic effects in part mediated by the Y1 receptor, whilst the
      influence of DSG affected lipolysis, lipogenesis and leptin secretion. Taken
      together, these studies support a local action for ghrelin isoforms on lipid and
      adipokine metabolism that further supports a cross talk between organs.

PMID- 18616715
TI  - Influence of birth size on body composition in early adulthood: the programming
      factors for growth and metabolism (PROGRAM)-study.
AB  - BACKGROUND/OBJECTIVES: Several studies have investigated the relationship of
      birth size with fat mass and lean body mass (LBM), but the findings differed
      greatly due to different ways of measuring FM and LBM, different study
      populations and age groups. We hypothesized that birth size has no influence on
      adult body composition, whereas weight gain during childhood has. METHODS: In the
      programming factors for growth and metabolism (PROGRAM)-study, a cohort of 312
      young adults, aged 18-24 years, FM and LBM were determined by dual energy X-ray
      absorptiometry (DXA). Subsequently, differences in FM and LBM were analysed in
      four subgroups, young adults either born small for gestational age with short
      stature (SGA-S) or with catch-up growth (SGA-CU), or born appropriate for
      gestational age (AGA) with idiopathic short stature (ISS) or with normal stature
      (controls). RESULTS: Age, gender, adult height SDS and adult weight SDS were
      significant positive determinants of FM and LBM, whereas weight gain during
      childhood was positively significant for FM and negatively for LBM. Birth weight
      SDS tended to be significant and birth length SDS was not. Weight gain during
      childhood was positively correlated with waist : hip ratio and trunk fat : total
      fat ratio. SGA-CU subjects had significantly higher FM and significantly lower
      LBM than controls. CONCLUSION: Weight gain during childhood is an important
      determinant of body composition in young adulthood, whereas birth size is less
      important. In clinical practice, too much weight gain in childhood should be
      prevented as it results in a relatively high fat mass, especially in children
      with catch-up growth in weight, like SGA-CU subjects.

PMID- 18616716
TI  - Influence of ethnicity on IGF-I and procollagen III peptide (P-III-P) in elite
      athletes and its effect on the ability to detect GH abuse.
AB  - CONTEXT: A method based on the two GH dependent markers, IGF-I and procollagen
      III peptide (P-III-P) has been proposed to detect exogenously administered GH. As
      previous studies involved predominantly white European elite athletes, it is
      necessary to validate the method in other ethnic groups. OBJECTIVE: To examine
      serum IGF-I and P-III-P in elite athletes of different ethnicities within 2 h of
      competing at national or international events. DESIGN: Cross-sectional
      observational study. SETTING: National and International sporting events.
      SUBJECTS: 1085 elite athletes of different ethnicities. INTERVENTION: Serum IGF-I
      and P-III-P were measured and GH-2000 discriminant function score was calculated.
      Effect of ethnicity was assessed. RESULTS: In men, IGF-I was 21.7 +/- 2.6% lower
      in Afro-Caribbeans than white Europeans (P < 0.0001) but there were no
      differences between other ethnic groups. In women, IGF-I was 14.2 +/- 5.1% lower
      in Afro-Caribbeans (P = 0.005) and 15.6 +/- 7.0% higher in Orientals (P = 0.02)
      compared with white Europeans. P-III-P was 15.2 +/- 3.5%, 26.6 +/- 6.6% and 19.3
      +/- 5.8% lower in Afro-Caribbean (P < 0.0001), Indo-Asian (P < 0.0001) and
      Oriental men (P = 0.001), respectively, compared with white European men. In
      women, P-III-P was 15.7 +/- 4.7% lower in Afro-Caribbeans compared to white
      Europeans (P =0.0009) but there were no differences between other ethnicities.
      Despite these differences, most observations were below the upper 99% prediction
      limits derived from white European athletes. All GH-2000 scores lay below the cut
      off limit proposed for doping. CONCLUSIONS: The GH-2000 detection method based on
      IGF-I and P-III-P would be valid in all ethnic groups.

PMID- 18616717
TI  - Inflammatory markers and visceral fat are inversely associated with maximal
      oxygen consumption in women with polycystic ovary syndrome (PCOS).
AB  - BACKGROUND: We investigated whether several different inflammatory markers
      including C-reactive protein (CRP) and fibrinogen and white blood cells (WBCs)
      count, are associated with maximal oxygen consumption (VO(2 max)) in women with
      polycystic ovary syndrome (PCOS). METHODS: In PCOS women (n = 124, 24.1 +/- 4.5
      year-old) VO(2 max) was measured during symptom-limited cardiopulmonary exercise
      test. Abdominal fat distribution was determined by ultrasound. Physical activity
      level was assessed by a standardized questionnaire. CRP was measured by
      immunoassays, fibrinogen by the Clauss method, and WBCs count with a Coulter
      counter. RESULTS: Pearson's analysis showed a significant correlation between
      VO(2 max) and logCRP (r = -0.437, P < 0.001), fibrinogen (r = -0.479, P < 0.001),
      and WBCs count (r = -0.438, P < 0.001). Multivariable logistic regression model
      showed that age (beta = -0.127, P = 0.005), AUC(INS )(beta = -0.335, P < 0.001),
      HDL-C (beta = 0.390, P < 0.001), physical activity score (beta = 0.238, P =
      0.002), visceral fat (beta =-0.184), P = 0.023), FAI (beta = -0.291, P = 0.028);
      CRP (beta = -0.216, P = 0.011), fibrinogen (beta = -0.113, P = 0.008) and WBCs
      count (beta = -0.177, P < 0.001) were significantly associated with VO(2 max).
      CONCLUSIONS: Acute-phase reactants, such as CRP and fibrinogen, and WBCs count
      were independently and inversely associated with a direct measure of
      cardiorespiratory fitness (VO(2 max)) in women with PCOS, even after adjustment
      for physical activity level and other potential confounding factors. These
      findings add to the growing body of evidence linking inflammation to
      cardiorespiratory fitness in PCOS women.

PMID- 18616718
TI  - Relationships between vascular resistance and energy deficiency, nutritional
      status and oxidative stress in oestrogen deficient physically active women.
AB  - OBJECTIVE: Oestrogen deficiency contributes to altered cardiovascular function in
      premenopausal amenorrheic physically active women. We investigated whether other
      energy deficiency-associated factors might also be associated with altered
      cardiovascular function in these women. DESIGN: A prospective observational study
      was completed at a research facility at the University of Toronto. PARTICIPANTS:
      Thirty-two healthy premenopausal women (18-35 years old) were studied; 9
      sedentary and ovulatory; 14 physically active and ovulatory; and 8 physically
      active and amenorrheic. MEASUREMENTS: We measured calf vascular resistance,
      resting heart rate, dietary energy intake, resting energy expenditure and serum
      measures of homocysteine, high-sensitivity C-reactive protein, oxidized low
      density lipoproteins, total T(3), ghrelin, leptin and insulin. RESULTS: Groups
      were similar (P > 0.05) in age (25.1 +/- 0.8 years; mean +/- SEM), weight (57.3
      +/- 1.1 kg), and BMI (21.4 +/- 0.3 kg/m(2)). Resting vascular resistance and
      ghrelin were highest (P < 0.05, main effect), and total T(3) and energy
      expenditure adjusted for fat free mass lowest (P < 0.05, main effect) in
      oestrogen deficient women. Using pooled data for stepwise multiple regression
      modelling: ghrelin and resting energy expenditure adjusted for fat free mass were
      associated with resting vascular resistance (R(2) = 0.398, P = 0.018); adjusted
      dietary energy intake was associated with peak-ischaemic vascular resistance
      (R(2) = 0.231, P = 0.015). Adjusted resting energy expenditure (r = 0.624, P <
      0.001) and total T(3) correlated (r = 0.427, P = 0.019) with resting heart rate.
      Homocysteine, high-sensitivity C-reactive protein and oxidized low-density
      lipoproteins were similar (P > 0.05, main effect) among the groups, and were
      unrelated to cardiovascular measures. CONCLUSION: Altered resting vascular
      resistance in premenopausal oestrogen deficient physically active amenorrheic
      women is not associated with vascular inflammation or oxidative stress, but
      rather with parameters that reflect metabolic allostasis and dietary intake,
      suggesting a potential role for chronic energy deficiency in vascular regulation.

PMID- 18616719
TI  - Mycobacterium abscessus infection secondary to mesotherapy.

PMID- 18616720
TI  - Successful use of radiotherapy for radiation-induced basal cell carcinoma of the
      scalp.

PMID- 18616721
TI  - Retroauricular milia en plaque: a rare presentation of lupus erythematosus.
AB  - Milia en plaque is a term used to describe an aggregation of milia occurring on
      an erythematous base usually localized in the retroauricular area. In most
      reported cases, no aetiological factors have been identified. We report the first
      case of milia en plaque associated with discoid lupus erythematosus occurring in
      the retroauricular site.

PMID- 18616722
TI  - Gnatophyma: a rare variant of phyma.
AB  - We report a case of a 44-year-old woman with an 8-year history of gnatophyma.
      Rosacea is a facial dermatosis that may present as flushing, erythema,
      telangiectases, papules, pustules and phyma. Phyma is considered the final
      evolution stage of rosacea and is a rare variant. Treatment of phyma with
      atypical localization may be a challenge for dermatologists in clinical practice.

PMID- 18616723
TI  - Interdigital pilonidal sinus in the foot.

PMID- 18616724
TI  - The functional role of nuclear factor kappa-kappaB1 -94 ins/del ATTG promotor
      gene polymorphism in Behcet's disease: an exploratory study.
AB  - Behcet's Disease (BD) is a systemic immunoinflammatory disease. The pathogenesis
      of BD is unknown, although raised levels of several pro-inflammatory cytokines
      have been reported. Nuclear factor kappa B (NF-kappaB) is a family of critical
      transcriptional factors involved in the regulation of a large variety of
      inflammatory responses and apoptosis. In this study we investigated the -94
      insertion/deletion ATTG promoter polymorphism of the NF-kappaB1 gene (NFKB1) in
      86 patients with BD and 100 healthy controls. The frequency of the -94ins ATTG
      (I) allele was 61.6% in patients with BD and 59% in controls and the frequency of
      the -94 del ATTG (D) allele was 38.4% in patients with BD and 41% in controls.
      The frequency of the -94ins ATTG (I) allele was significantly higher in patients
      with ocular involvement (P = 0.03). In the genotype study, the overall
      frequencies of II, ID and DD were 40.7%, 41.9%, and 17.4% in the patient group
      and 30%, 58% and 12% in the control group (P: 0.08). The II genotype was
      significantly higher in patients with ocular involvement, genital ulcers or
      papulopustular lesions. The frequency of the II, ID and DD genotypes showed no
      marked difference in patients with erythema nodosum, pathergy positivity,
      arthritis or vascular involvement. No difference was found for gender, positive
      family history or age at disease onset. This study provides evidence that the 
      94ins/del ATTG promoter polymorphism of NFKB1 may have functional consequences in
      BD, especially in patients with ocular involvement.

PMID- 18616725
TI  - Immunohistochemical staining for the differentiation of subungual keratoacanthoma
      from subungual squamous cell carcinoma.
AB  - BACKGROUND: Subungual keratotic tumours are rare. The clinical and histological
      distinctions between subungual keratoacanthomas (SUKAs) and subungual squamous
      cell carcinomas (SCCs) are important, but often difficult. Adequate methods of
      differentiation between the two are required, both for the purpose of management
      and for assessment of prognosis. AIM: To establish the value of
      immunohistochemical staining patterns of proliferating cells to distinguish
      between SUKAs and subungual SCCs. METHODS: In total, 20 keratotic tumours from 20
      patients were examined with immunohistochemical staining techniques using bcl-2,
      Ki67 and p53. RESULTS: Of 20 patients, 4 had SUKAs, 5 had cutaneous KAs, 6 had
      subungual SCCs and 5 had cutaneous SCCs. Our results showed that a high index of
      staining of p53 favours the diagnosis of subungual SCC over SUKA. CONCLUSION:
      SUKAs do not express Ki67 strongly whereas some subungual SCCs do. Thus we
      conclude that immunohistochemistry for p53 and Ki67 may help distinguish between
      a subungual SCC and a SUKA.

PMID- 18616726
TI  - Topical diclofenac 3% gel plus cryotherapy for treatment of multiple and
      recurrent actinic keratoses.
AB  - This paper reviews retrospectively the results obtained in a case series of
      multiple refractory actinic keratoses (AKs), treated sequentially with topical
      diclofenac 3% gel followed by cryotherapy. In total, 29 patients were reviewed;
      all had >or= 5 lesions (mean 8.2; range 5-12) and a long-term history of
      recurrence after repeated cryotherapy. After a first-line, 12 week treatment
      phase with diclofenac 3% gel alone, the number of AKs per subject was reduced to
      an average of 1.5 AKs (range 0-5), with complete clearance of lesions in 21 cases
      (71%). Patients showing incomplete response to the above treatment (n = 8) then
      received liquid-nitrogen ablation for all residual lesions. This procedure
      resulted in complete clearance of all cases. Significantly, during the post
      treatment follow-up period, patients had no AK recurrences for an average of 10
      months (range 6-20). Sequential treatment with diclofenac 3% gel followed by
      cryotherapy may therefore represent an effective approach for the management of
      multiple refractory AKs.

PMID- 18616727
TI  - Disseminated Cryptococcus infection in a liver-transplant recipient presenting
      with a chronic scalp eruption.

PMID- 18616728
TI  - Roll with it: antiperspirant detection of axillary lymphadenopathy.

PMID- 18616729
TI  - Cutaneous mastocytosis in human immunodeficiency virus: an unfortunate
      coincidence?
AB  - We report the case of a young man who developed cutaneous mastocytosis on the
      trunk and limbs after an episode of severe sunburn. He was diagnosed with human
      immunodeficiency virus (HIV) shortly afterwards. We discuss this interesting and
      previously unreported temporal relationship between the development of
      mastocytosis and recent HIV infection, speculating on the potential pathogenetic
      mechanisms of association.

PMID- 18616730
TI  - Cutaneous dissemination of nasal NK/T-cell lymphoma in a young girl.
AB  - In Europe and the USA, the incidence of primary nasal natural killer (NK)/T-cell
      lymphoma is rare. The skin is one of the predilection sites for dissemination.
      Cutaneous dissemination is a poor prognostic sign and is consistently fatal. We
      describe the case of a 17-year-old white German girl with a primary nasal NK/T
      cell lymphoma and cutaneous dissemination. She presented with multiple
      maculopapular patches involving the trunk and thighs, and a 4-week history of
      headache, fever and fatigue. Biopsies of the skin and the nasal mucosa were
      taken. Pathological examination of both specimens revealed a NK/T-cell lymphoma.
      Epstein-Barr virus RNA was detected in the lymphoma cells by in situ
      hybridization. Unfortunately, the patient died of disease within 1 week.

PMID- 18616731
TI  - Acquired perforating dermatosis appearing as elastosis perforans serpiginosa and
      perforating folliculitis.

PMID- 18616732
TI  - Pyogenic granuloma-like lesions caused by capecitabine therapy.

PMID- 18616733
TI  - Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2
      encompassing LAF4.
AB  - Nievergelt syndrome (NS) is an autosomal dominant mesomelic dysplasia
      characterized by specific deformities of the radius, ulna, fibula and a rhomboid
      shape of the tibia. Phenotypically overlapping conditions such as mesomelic
      dysplasia, Savarirayan-type (MIM 605274), have been described, but their
      pathogenesis also remains unknown. We report on a girl with fibular agenesis,
      severely abnormal, triangular tibiae, urogenital tract malformations, failure to
      thrive, convulsions and recurrent apnoeas leading to respiratory arrest at the
      age of 4 months. Her skeletal findings correspond to those of the mesomelic
      dysplasia, Savarirayan-type recently described in two patients. In addition to
      the skeletal findings, our patient had central nervous system manifestations and
      developmental anomalies of the urogenital tract. In the patient described in this
      study, array comparative genomic hybridization (CGH) analysis revealed a de novo
      interstitial microdeletion of 500 kb on chromosome 2q11.1 containing the
      LAF4/AFF3 (lymphoid-nuclear-protein-related AF4) gene. In situ hybridization
      analysis of Laf4 in mouse embryos revealed expression in the developing brain, in
      the limb buds and in the zeugopod corresponding to the limb phenotype.
      Haploinsufficiency for LAF4/AFF3 is associated with limb, brain and urogenital
      malformations and specific changes of the tibia that are part of the NS spectrum.

PMID- 18616734
TI  - Attitudes antecedent to transition to self-management of a chronic genetic
      disorder.
AB  - Marfan syndrome (MFS) is the exemplar of chronic genetic disorders that require
      multiorgan system management by health care providers (HCPs) and lifelong self
      management by affected individuals. This article describes the ways to facilitate
      transition to self-management (TSM) by the adolescent with MFS. This thematic
      content analysis uses data collected for a larger grounded theory investigation
      of TSM of a chronic genetic disorder in adolescents and focuses on the system
      issues related to transition. A total sample of 107 included three groups of
      participants: parents (n = 39), adolescents (n = 37, ages 14-21 years) and young
      adults (n = 16, ages 22-34 years) with MFS, and HCPs (n = 15), including
      physicians, genetic counselors, and nurses. Data were derived from 180
      transcripts of audiotaped interviews and a sociodemographic survey. Frames of
      mind that are antecedent to transition were belief in the diagnosis, wanting to
      understand and appreciate the cause and effect of MFS, and willing to share
      responsibility in problem solving. These frames of mind occurred primarily within
      the context of the family relationship. Parents taught children self-surveillance
      as 'listening to one's body'. The parent's fears and need to stay involved in the
      child's health care slowed the child's independent work on self-management
      responsibilities. A systematic, institutionalized transition program for
      adolescents might involve parents and the child soon after diagnosis and
      incrementally build acknowledgment, understanding, and rapport.

PMID- 18616735
TI  - Phenotypic discordance in a pair of monozygotic twins with Huntington's disease.

PMID- 18616736
TI  - Rectal cancer in young adults: a series of 102 patients at a tertiary care centre
      in India.
AB  - OBJECTIVE: Rectal cancer in young patients is uncommon. There is little
      information on rectal cancer in young adults in India. The aim of this study was
      to determine the relative incidence of rectal cancer in young patients in India
      and identify any differences in histological grade and pathological stage between
      younger and older cohorts. METHOD: All adult patients presenting at a tertiary
      colorectal unit with primary rectal adenocarcinoma between September 2003 and
      August 2007 were included. Patients were divided into two groups: 40 years and
      younger, and older than 40 years. Details regarding patient demographics,
      preoperative assessment, management and tumour grade and stage were obtained from
      a prospectively maintained database. RESULTS: One hundred and two of 287 patients
      (35.5%) were 40 or younger at presentation. Younger patients were more likely to
      present with less favourable histological features (52.0% vs 20.5% (P < 0.001))
      and low rectal tumours (63.0% vs 50.0%) (P = 0.043), but were equally likely to
      undergo curative surgery compared to the older group (P = 0.629). Younger
      patients undergoing surgery had a higher pathological T stage (T0-2 18.9%, T3
      62.3%, T4 19.7% vs 34.5%, 56.0%, 9.5%) (P = 0.027) and more advanced pathological
      N stage (N0 31.1%, N1 41.0%, N2 27.9% vs 53.4%, 26.7%, 17.2%) (P = 0.014).
      CONCLUSION: The relative number of young patients with rectal cancer in this
      Indian series is higher than figures reported in western populations. The reasons
      for this are not clear. The histopathological features of rectal tumours in young
      patients in this study are consistent with similar studies in Western
      populations.

PMID- 18616737
TI  - Emergency laparoscopic surgery for complicated diverticular disease.
AB  - OBJECTIVE: The aim of this study was to analyse the outcome of emergency
      laparoscopic surgical management of complicated diverticular disease. METHOD: A
      prospectively collected electronic database of all colorectal laparoscopic
      procedures between April 2001 and September 2007 has been used to identify
      outcomes in patients presenting with complicated diverticular disease. RESULTS:
      Sixty-six patients (28 men), median age 69 years (23-95), ASA grade II (12), III
      (38), IV (16) have undergone emergency surgery for complicated diverticulitis-
      Hinchey grades I (27), II (29), III (7) and diverticular bleeding (3) over a
      6(1/2)-year period: 43 high anterior resections, 17 Hartmann's resections and
      seven low anterior resections. Diverticular fistulas were seen in 16 patients:
      colovaginal (7), colovesical (2), colo-fallopian (4), entero-colic (3). The
      median operation time was 110 min (45-195 min). There was one conversion to open
      surgery. Postoperative analgesia was provided by intravenous Paracetamol in 33
      patients (50%), patient-controlled analgesia in 24 (36%), oral Paracetamol and
      Oramorph (12%) and epidural opioid infusion (1.5%). The median time to normal
      diet was 24 h (4 h-6 days) and median hospital stay 5 days (2-30). There were two
      deaths (3.3%); anastomotic leak, ventricular fibrillation (VF) cardiac arrest.
      Other complications included: wound infection eight (12%), anastomotic leak four
      (8%), port-site hernia one and one case of Clostridium difficile colitis
      requiring colectomy. There were five (7.5%) returns to theatre and two
      readmissions (3%). CONCLUSION: Laparoscopic resectional surgery in complicated
      diverticular disease is a feasible, safe and a largely predictable operation that
      allows for early hospital discharge and, in our opinion, improved patient care.
      We are encouraged to continue to offer our patients the option of an emergency
      laparoscopic resection.

PMID- 18616738
TI  - Response of a group of Sichuan snub-nosed monkeys to commercial logging in the
      Qinling Mountains, China.
AB  - Habitat destruction is one of the greatest threats to primates worldwide. To
      understand the impact of forest logging on the habitat use of primates in
      temperate mixed forest, we compared the range, habitat used, population size, and
      diet of a troop (ERT) of Sichuan snub-nosed monkeys (Rhinopithecus roxellana) in
      the Qinling Mountains before (1989), during (1997), and after (2002-2003)
      commercial logging. Logging significantly changed the composition of the forest
      and the food supply for the troop. Some areas were heavily logged and formed
      patches in the forest that lacked canopy cover. The troop moved 7 km away from
      their original range when logging took place and returned to their original range
      after logging stopped, but they avoided heavily logged areas that lacked canopy
      cover. Their movement indicated some degree of site fidelity in this species.
      Diet and home range changed after logging, but the population size remained
      stable, which suggests that this species has some ability to adapt to habitat
      changes. Our results may reflect a natural flexibility in primates to adapt to
      the changing food resources in temperate areas with marked seasonal variations in
      food availability and distribution. This flexibility may have contributed to
      their higher degree of resilience to habitat alterations caused by human
      activities compared with tropical forest primates that have a more specialized
      diet. Our findings provide important baseline information that will help decision
      makers in their efforts to conserve primates, especially in temperate regions,
      and to sustainably manage primate habitat.

PMID- 18616739
TI  - Protection of mammal diversity in Central America.
AB  - Central America is exceptionally rich in biodiversity, but varies widely in the
      attention its countries devote to conservation. Protected areas, widely
      considered the cornerstone of conservation, were not always created with the
      intent of conserving that biodiversity. We assessed how well the protected-area
      system of Central America includes the region's mammal diversity. This first
      required a refinement of existing range maps to reduce their extensive errors of
      commission (i.e., predicted presences in places where species do not occur). For
      this refinement, we used the ecological limits of each species to identify and
      remove unsuitable areas from the range. We then compared these maps with the
      locations of protected areas to measure the habitat protected for each of the
      region's 250 endemic mammals. The species most vulnerable to extinction-those
      with small ranges-were largely outside protected areas. Nevertheless, the most
      strictly protected areas tended toward areas with many small-ranged species. To
      improve the protection coverage of mammal diversity in the region, we identified
      a set of priority sites that would best complement the existing protected areas.
      Protecting these new sites would require a relatively small increase in the total
      area protected, but could greatly enhance mammal conservation.

PMID- 18616740
TI  - Impacts of chronic anthropogenic noise from energy-sector activity on abundance
      of songbirds in the boreal forest.
AB  - The effects of human activities in forests are often examined in the context of
      habitat conversion. Changes in habitat structure and composition are also
      associated with increases in the activity of people with vehicles and equipment,
      which results in increases in anthropogenic noise. Anthropogenic noise may reduce
      habitat quality for many species, particularly those that rely on acoustic
      signals for communication. We compared the density and occupancy rate of forest
      passerines close to versus far from noise-generating compressor stations and
      noiseless well pads in the boreal forest of Alberta, Canada. Using distance-based
      sampling, we found that areas near noiseless energy facilities had a total
      passerine density 1.5 times higher than areas near noise-producing energy sites.
      The White-throated Sparrow (Zonotrichia albicollis), Yellow-rumped Warbler
      (Dendroica coronata), and Red-eyed Vireo (Vireo olivaceus) were less dense in
      noisy areas. We used repeat sampling to estimate occupancy rate for 23 additional
      species. Seven had lower conditional or unconditional occupancy rates near noise
      generating facilities. One-third of the species examined showed patterns that
      supported the hypothesis that abundance is influenced by anthropogenic noise. An
      additional 4 species responded negatively to edge effects. To mitigate existing
      noise impacts on birds would require approximately $175 million. The merits of
      such an effort relative to other reclamation actions are discussed. Nevertheless,
      given the $100 billion energy-sector investment planned for the boreal forest in
      the next 10 years, including noise suppression technology at the outset of
      construction, makes noise mitigation a cost-effective best-management practice
      that might help conserve high-quality habitat for boreal birds.

PMID- 18616741
TI  - Interspecific patterns of genetic diversity in birds: correlations with
      extinction risk.
AB  - Birds are frequently used as indicators of ecosystem health and are the most
      comprehensively studied class in the animal kingdom. Nevertheless, a
      comprehensive, interspecific assessment of the correlates of avian genetic
      diversity is lacking, even though indices of genetic diversity are of
      considerable interest in the conservation of threatened species. We used
      published data on variation at microsatellite loci from 194 bird species to
      examine correlates of diversity, particularly with respect to conservation status
      and population size. We found a significant decline in mean heterozygosity with
      increasing extinction risk, and showed, by excluding species whose heterozygosity
      values were calculated with heterospecific primers, that this relationship was
      not dependent on ascertainment bias. Results of subsequent regression analyses
      suggested that smaller population sizes of threatened species were largely
      responsible for this relationship. Thus, bird species at risk of extinction are
      relatively depauperate in terms of neutral genetic diversity, which is expected
      to make population recovery more difficult if it reflects adaptive genetic
      variation. Conservation policy will need to minimize further loss of diversity if
      the chances of saving threatened species are to be maximized.

PMID- 18616742
TI  - Calculating biologically accurate mitigation credits: insights from the
      California tiger salamander.
AB  - Current conservation mitigation plans often fail to ensure full in-kind habitat
      replacement for endangered species, which suggests the need for improved methods
      for calculating mitigation credits. A simple, yet biologically meaningful method
      for calculating mitigation credits would be to let the number of mitigation
      credits assigned to a parcel of land scale with the reproductive value of the
      individuals occupying that parcel. This can be accomplished by dividing the
      population into 2 or more subdivisions with different reproductive values,
      calculating the densities of these subdivisions as a function of one or more
      habitat parameters, and then forming a weighted sum of these densities such that
      each density distribution is weighted by the reproductive value of its respective
      subdivision of the population. This weighted sum is the density distribution of
      reproductive value, and by integrating it over a particular parcel, one can
      determine the mitigation value of that parcel. We carried out this procedure for
      a population of California tiger salamanders (Ambystoma californiense), with
      distance from breeding site as our habitat parameter and the 3 visually
      identifiable age classes (adults, juveniles, and metamorphs) as our population
      subdivisions. This led to a density distribution of reproductive value that
      decreased exponentially with increasing distance from a breeding site. Mitigation
      strategies derived from this function will be more likely to ensure the
      persistence of California tiger salamander populations than current approaches,
      which assign all land within 1.6 km of a breeding site the same mitigation value.
      Use of the density distribution of reproductive value as a basis for mitigation
      plans is a procedure that can be applied to all endangered species, and it should
      improve the quality of mitigation decisions.

PMID- 18616743
TI  - The importance of taboos and social norms to conservation in Madagascar.
AB  - Informal institutions governing the use of wild species are present in many
      societies. A system of prohibitions known as fady is central to Malagasy culture.
      We examined whether fady that relate to the use of natural resources in the
      eastern rainforests of Madagascar play an important conservation role.
      Prohibitions ranged from strict taboos in which a species or area was forbidden
      by the ancestors to social norms that concerned acceptable behavior when
      harvesting wild species. Strict taboos offered real protection to threatened
      species, such as the lemur Propithecus edwardsi and the carnivore Cryptoprocta
      ferox. Taboos also reduced pressure on some economically important endemic
      species by preventing their sale or limiting the harvest season. Despite their
      value for conservation, the taboos did not appear to originate from attempts to
      sustainably manage resources. Nevertheless, social norms, in which the sanction
      was social disapproval rather than supernatural retribution, encouraged
      sustainable harvesting practices for tenrecs (Tenrec ecudatus) and pandans
      (Pandanus spp.). Unfortunately, the social norms concerning methods of harvesting
      pandans appeared to be breaking down in villages surrounding Ranomafana National
      Park, and we suggest that the imposition of external conservation rules is
      weakening traditional management. Informal institutions are important to
      conservation because they suggest ways of improving cultural understanding and
      conservation communication. Food taboos influence societal preferences, which
      affect the wider demand for a species. Most important, where capacity to enforce
      external conservation rules is limited, informal institutions may provide the
      only effective regulations. Informal institutions should receive greater
      attention from conservation biologists so that local people's conservation roles
      can be acknowledged fairly and so that potential synergies with conservation
      objectives can be realized.

PMID- 18616744
TI  - Understanding trait-dependent community disassembly: dung beetles, density
      functions, and forest fragmentation.
AB  - Anthropogenic disturbances such as fragmentation are rapidly altering
      biodiversity, yet a lack of attention to species traits and abundance patterns
      has made the results of most studies difficult to generalize. We determined
      traits of extinction-prone species and present a novel strategy for classifying
      species according to their population-level response to a gradient of disturbance
      intensity. We examined the effects of forest fragmentation on dung beetle
      communities in an archipelago of 33 islands recently created by flooding in
      Venezuela. Species richness, density, and biomass all declined sharply with
      decreasing island area and increasing island isolation. Species richness was
      highly nested, indicating that local extinctions occurred nonrandomly. The most
      sensitive dung beetle species appeared to require at least 85 ha of forest, more
      than many large vertebrates. Extinction-prone species were either large-bodied,
      forest specialists, or uncommon. These explanatory variables were unrelated,
      suggesting at least 3 underlying causes of extirpation. Large species showed high
      wing loading (body mass/wing area) and a distinct flight strategy that may
      increase their area requirements. Although forest specificity made most species
      sensitive to fragmentation, a few persistent habitat generalists dispersed across
      the matrix. Density functions classified species into 4 response groups on the
      basis of their change in density with decreasing species richness. Sensitive and
      persistent species both declined with increasing fragmentation intensity, but
      persistent species occurred on more islands, which may be due to their higher
      baseline densities. Compensatory species increased in abundance following the
      initial loss of sensitive species, but rapidly declined with increasing
      fragmentation. Supertramp species (widespread habitat generalists) may be poor
      competitors but strong dispersers; their abundance peaked following the decline
      of the other 3 groups. Nevertheless, even the least sensitive species were
      extirpated or rare on the smallest and most isolated islands.

PMID- 18616745
TI  - Ecological and economic services provided by birds on Jamaican Blue Mountain
      coffee farms.
AB  - Coffee farms can support significant biodiversity, yet intensification of farming
      practices is degrading agricultural habitats and compromising ecosystem services
      such as biological pest control. The coffee berry borer (Hypothenemus hampei) is
      the world's primary coffee pest. Researchers have demonstrated that birds reduce
      insect abundance on coffee farms but have not documented avian control of the
      berry borer or quantified avian benefits to crop yield or farm income. We
      conducted a bird-exclosure experiment on coffee farms in the Blue Mountains,
      Jamaica, to measure avian pest control of berry borers, identify potential
      predator species, associate predator abundance and borer reductions with
      vegetation complexity, and quantify resulting increases in coffee yield. Coffee
      plants excluded from foraging birds had significantly higher borer infestation,
      more borer broods, and greater berry damage than control plants. We identified 17
      potential predator species (73% were wintering Neotropical migrants), and 3
      primary species composed 67% of migrant detections. Average relative bird
      abundance and diversity and relative resident predator abundance increased with
      greater shade-tree cover. Although migrant predators overall did not respond to
      vegetation complexity variables, the 3 primary species increased with proximity
      to noncoffee habitat patches. Lower infestation on control plants was correlated
      with higher total bird abundance, but not with predator abundance or vegetation
      complexity. Infestation of fruit was 1-14% lower on control plants, resulting in
      a greater quantity of saleable fruits that had a market value of US$44-$105/ha in
      2005/2006. Landscape heterogeneity in this region may allow mobile predators to
      provide pest control broadly, despite localized farming intensities. These
      results provide the first evidence that birds control coffee berry borers and
      thus increase coffee yield and farm income, a potentially important conservation
      incentive for producers.

PMID- 18616746
TI  - Captive breeding, reintroduction, and the conservation of amphibians.
AB  - The global amphibian crisis has resulted in renewed interest in captive breeding
      as a conservation tool for amphibians. Although captive breeding and
      reintroduction are controversial management actions, amphibians possess a number
      of attributes that make them potentially good models for such programs. We
      reviewed the extent and effectiveness of captive breeding and reintroduction
      programs for amphibians through an analysis of data from the Global Amphibian
      Assessment and other sources. Most captive breeding and reintroduction programs
      for amphibians have focused on threatened species from industrialized countries
      with relatively low amphibian diversity. Out of 110 species in such programs, 52
      were in programs with no plans for reintroduction that had conservation research
      or conservation education as their main purpose. A further 39 species were in
      programs that entailed captive breeding and reintroduction or combined captive
      breeding with relocations of wild animals. Nineteen species were in programs with
      relocations of wild animals only. Eighteen out of 58 reintroduced species have
      subsequently bred successfully in the wild, and 13 of these species have
      established self-sustaining populations. As with threatened amphibians generally,
      amphibians in captive breeding or reintroduction programs face multiple threats,
      with habitat loss being the most important. Nevertheless, only 18 out of 58
      reintroduced species faced threats that are all potentially reversible. When
      selecting species for captive programs, dilemmas may emerge between choosing
      species that have a good chance of surviving after reintroduction because their
      threats are reversible and those that are doomed to extinction in the wild as a
      result of irreversible threats. Captive breeding and reintroduction programs for
      amphibians require long-term commitments to ensure success, and different
      management strategies may be needed for species earmarked for reintroduction and
      species used for conservation research and education.

PMID- 18616747
TI  - A meta-analysis of the effects of ultraviolet B radiation and its synergistic
      interactions with pH, contaminants, and disease on amphibian survival.
AB  - Human alterations to natural systems have resulted in a loss of biological
      diversity around the world. Amphibian population losses have been more severe
      than those of birds and mammals. Amphibian population declines are likely due to
      many factors including habitat loss, disease, contaminants, introduced species
      and ultraviolet-B (UVB) radiation. The effect of UVB, however, varies widely
      among species and can vary within populations of the same species or at different
      life-history stages. This variation has often led to opposing conclusions about
      how UVB affects amphibians. We used meta-analysis techniques to explore the
      overall effects of UVB radiation on survival in amphibians. We also used recently
      developed factorial meta-analytic techniques to quantify potential interactions
      between UVB radiation and other stressors on amphibians. Ultraviolet-B radiation
      reduced survival of amphibians by 1.9-fold compared with shielded controls.
      Larvae were more susceptible to damage from UVB radiation compared with embryos,
      and salamanders were more susceptible compared with frogs and toads. Furthermore,
      UVB radiation interacted synergistically with other environmental stressors and
      resulted in greater than additive effects on survival when 2 stressors were
      present. Our results suggest that UVB radiation is an important stressor in
      amphibians, particularly in light of potential synergisms between UVB and other
      stressors in amphibian habitats.

PMID- 18616748
TI  - Dual nasal sidewall and lip defects combined into a single arcuate advancement
      flap.
AB  - The authors have indicated no significant interest with commercial supporters.

PMID- 18616749
TI  - Expression of Smad protein by normal skin fibroblasts and hypertrophic scar
      fibroblasts in response to transforming growth factor beta1.
AB  - BACKGROUND: Smad proteins are important intracellular mediators of transforming
      growth factor (TGF)-beta signaling. Little has been known about the specific
      relationship between TGF-beta and TGF-beta/Smad signaling in hypertrophic scars.
      OBJECTIVE: The objective was to investigate the expression of Smads and the
      specific relationship between TGF-beta and TGF-beta/Smad signaling in
      hypertrophic scars. METHODS: In this study, we initially determined the
      endogenous protein levels of Smad2 and Smad7 in hypertrophic scar fibroblast
      (HSFs) and normal skin fibroblast (NSFs). Second, we stimulated HSFs and NSFs
      with recombinant human TGF-beta1 for 24 hours to determine whether the TGF-beta1
      could potentiate its effect by further stimulating the production of Smad by
      reverse transcription-polymerase chain reaction and Western blot analysis.
      RESULTS: When compared with NSFs, the endogenous expression of Smad2 in HSFs was
      up-regulated and TGF-beta1 could further stimulate the production of Smad2.
      Although the levels of Smad7 were similar between HSFs and NSFs, TGF-beta1 up
      regulated the expression of Smad7 for NSFs only, with no discernible effect on
      HSFs. These changes were paralleled by a significant increase in cytoplasm-to
      nuclear translocation of Smad2. CONCLUSION: These data substantiated the model of
      an autocrine positive loop in hypertrophic scars pathogenesis. The authors have
      indicated no significant interest with commercial supporters.

PMID- 18616753
TI  - The red blood cell distribution width is associated with serum levels of thyroid
      stimulating hormone in the general population.

PMID- 18616754
TI  - Performance evaluation of the Sysmex XS-1000i automated haematology analyser.
AB  - The Sysmex XS-1000i is a compact new, fully automated haematology analyser,
      designed to generate complete blood counts with five-part leucocyte differential.
      In our study, a Sysmex XS-1000i instrument was evaluated according to Clinical
      Laboratory Standards Institute (CLSI) and International Council for
      Standardization in Haematology (ICSH) guidelines. Precision, carry-over and
      linearity were determined. Using a total of 700 patient samples, results from the
      Sysmex XS-1000i were compared with those from a Sysmex XE-2100, an Abbott Cell
      Dyn 4000 and the manual reference leucocyte differential. Using quality control
      material, total and within-run imprecision was less than 3% except for platelets.
      The system demonstrated good linearity over the entire reporting range and no
      carry-over (<0.5%). The Sysmex XS-1000i showed good correlation with XE-2100, CD
      4000 and the manual reference leucocyte differential. Overall flagging
      sensitivity and specificity were 91% and 48%, respectively. In conclusion, the
      Sysmex XS-1000i demonstrated good analytical performance, is able to generate a
      complete blood count with five-part differential on low blood volumes and has
      considerable back-up capacity.

PMID- 18616755
TI  - Expression level of lipoprotein lipase in Chinese patients with chronic
      lymphocytic leukemia and its correlation with other prognostic factors.
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult form of leukemia in
      the Western world, however, infrequent in the Eastern. It shows a remarkable
      heterogeneity, with some patients having an almost normal lifespan, others
      surviving only several years after diagnosis despite intensive therapy. To
      investigate lipoprotein lipase (LPL) expression level in Chinese patients with
      CLL and its correlation with other prognostic factors, including immunoglobulin
      heavy-chain variable region (IgVH) mutation status, Binet stages, ZAP-70 protein
      and CD38 expression level, semiquantitative RT-PCR was used to detect LPL
      expression in peripheral blood samples of 58 Chinese patients with CLL. LPL
      expression level was significantly correlated with IgVH mutational status (r =
      0.348, P = 0.010), Binet stages (r = 0.276, P = 0.036), ZAP-70 protein (r =
      0.431, P = 0.001) and CD38 (r = 0.546, P < 0.001). Patients with unmutated IgVH
      genes had higher expression of LPL than patients with IgVH mutations. The higher
      expression level of LPL was also associated with higher level of ZAP-70 and CD38,
      and more aggressive Binet stage. We also analyzed LPL expression in different
      cytogenetic subgroups. Higher LPL level was found in patients with unfavorable
      cytogenetic aberrations (deletion in 17p13 or 11q22) in contrast to lower level
      in good risk cytogenetics (deletion in 13q as the sole abnormality) (r = 0.404, P
      = 0.002). It was showed that LPL expression correlates with IgVH mutational
      status and other clinical or laboratory prognostic factors, and might be applied
      for the assessment of prognosis in patients with CLL.

PMID- 18616756
TI  - Orthodontic extraction of mandibular third molar to avoid nerve injury and
      promote periodontal healing.
AB  - AIM: Impacted mandibular third molar extraction is a common procedure in oral
      surgery, not without risk of nerve injury and periodontal defects on the distal
      aspect of the adjacent second molar. The "orthodontic extraction" is proposed as
      a method to avoid mandibular nerve injury during the extraction of a deeply
      embedded third molar and to prevent or limit such periodontal problems. MATERIAL
      AND METHODS: A 28-year-old man presented a deeply impacted left mandibular third
      molar that required extraction. Radiographs revealed a very slight quantity of
      bone at the distal surface of the adjacent second molar. The third molar was
      extruded according to the "orthodontic extraction" technique. A 3-month retention
      phase elapsed to ensure adequate bone maturation and the tooth was finally
      extracted. RESULTS: No neurological complications occurred. A minimal residual
      bone defect at the distal surface of the adjacent second molar was detected
      radiographically both post-operatively and at the 3-year follow-up. CONCLUSIONS:
      Orthodontic extraction makes third molar removal easier and has no neurological
      risk. This procedure, followed by a 3-month retention phase, appears to be
      effective in preventing or limiting the development of periodontal problems on
      the distal aspect of the adjacent second molar.

PMID- 18616757
TI  - Clonal stability of Porphyromonas gingivalis in untreated periodontitis.
AB  - OBJECTIVES: The objective of the present investigation was to study the clonal
      stability of Porphyromonas gingivalis in a population of Indonesian subjects,
      deprived of dental care and with varying degrees of periodontitis over a period
      of 8 years. MATERIAL AND METHODS: In 1994, 105 subjects and in 2002, 103 subjects
      were P. gingivalis culture positive. Multiple isolates from each of these
      subjects were used for amplified fragment length polymorphism (AFLP) typing.
      RESULTS: Sixty-six individuals were P. gingivalis culture positive at both time
      points. In 31 subjects (47%) an exact identical P. gingivalis genotype
      distribution was found in 1994 and in 2002. In 26 of these subjects one genotype,
      in eight subjects two identical genotypes were found at both time points. In 70%
      of the subjects at least one P. gingivalis genotype was found in 1994 and 2002,
      whereas other genotypes were either newly detected or were no longer detectable.
      Identical genotypes were found in 26% of the sibships. Clonal stability in
      siblings was 39%. Horizontal transmission of P. gingivalis was only found in 2002
      and was low (11%). In total, 56 P. gingivalis genotypes were identified in 1994
      and 61 in 2002. Twenty-four appeared unique, whereas other genotypes were found
      in multiple subjects within as well as without families. One genotype occurred in
      11 different subjects. CONCLUSIONS: The clonal stability of P. gingivalis under
      natural conditions is high. Complete different genotype distribution was found in
      only 27% of the subjects. Transmission of P. gingivalis occurred frequently among
      siblings but not among spouses.

PMID- 18616758
TI  - 5-year clinical experience with BTI dental implants: risk factors for implant
      failure.
AB  - OBJECTIVES: The aims of this study were to identify with appropriate statistical
      tests the risk factors associated with implant failure and to evaluate the long
      term survival of dental implants using implant loss as an outcome variable and
      performing an implant-, surgery- and patient-based analysis of failures. MATERIAL
      AND METHODS: A retrospective cohort study design was used. One thousand sixty
      patients received 5787 BTI implants during the years of 2001-2005 in Vitoria,
      Spain. The potential influence of demographic items, clinical items, surgery
      dependent items and prosthetic variables on implant survival was studied. Implant
      survival was analysed using a life-table analysis. Cox proportional hazards
      regression was used to identify risk factors related to implant failure. RESULTS:
      Smoking habits, implant position, implant staging (two-stage implants) and the
      implementation of special techniques were statistically correlated with lower
      implant survival rates. Two risk factors associated with implant failure were
      detected in this study: implant staging (two-stage implants) and the use of
      special techniques. Additionally, the overall survival rates of BTI implants were
      99.2%, 96.4% and 96% for the implant-, surgery- and patient-based analysis,
      respectively. Totally, 28 out from 5787 implants (0.48%) were lost during the
      observation period. Most of the patients with implant failure (69.6%) presented
      chronic or aggressive periodontitis. CONCLUSIONS: Implant staging and the use of
      special techniques are risk factors for implant failure.

PMID- 18616759
TI  - Comparison of CD23 staining patterns in Merkel cell carcinoma and non-cutaneous
      small cell carcinoma.
AB  - BACKGROUND: During our daily practice, we observed that cluster designation 23
      (CD23) (clone BU38) labels Merkel cells in normal skin. In this study, we
      examined the expression of CD23 in Merkel cell carcinoma (MCC) and assessed its
      usefulness in distinguishing MCC from non-cutaneous small cell carcinoma (SMCC).
      METHODS: Immunohistochemical staining of CD23 was performed on a total of 33
      MCCs, 22 SMCCs and 5 carcinoid tumors. RESULTS: CD23 reactivity was present in 32
      of 33 (97%) MCCs, 18 of 22 (82%) SMCCs and 5 of 5 (100%) carcinoid tumors. In
      MCC, 19 cases (59%) showed a predominance of perinuclear dot-like staining
      similar to cytokeratin 20, 3 (9%) showed mostly cytoplasmic staining and 10 (31%)
      displayed a combination of perinuclear dot-like and cytoplasmic staining. In
      contrast, all CD23-positive SMCCs and carcinoid tumors showed a diffuse
      cytoplasmic staining. There was a significant difference in the CD23 staining
      patterns between MCC and SMCC (p < 0.0001). CONCLUSION: CD23 is expressed in the
      majority of MCC, SMCC and carcinoid tumor irrespective of clinical outcome. The
      distinct punctate CD23 staining for MCC may be helpful in differentiating it from
      SMCC. To our knowledge, this is the first study to show the expression of CD23 in
      neuroendocrine tumors.

PMID- 18616760
TI  - Androgen receptor overexpression in Becker nevus: histopathologic and
      immunohistochemical analysis.
AB  - BACKGROUND: Becker nevus (BN) is a unilateral, hairy, pigmented cutaneous
      hamartoma that frequently appears in adolescence. Several features of BN suggest
      that increased androgen sensitivity plays a role in its pathogenesis. There have
      been only a few studies of histopathologic and immunohistochemical
      characteristics of BN, and the etiopathogenesis has not been fully established.
      METHODS: Two-millimeter punch biopsies were taken from lesional and perilesional
      normal skin of 30 patients diagnosed as having BN. Fifteen skin samples each of
      lentigo and cafe au lait spots were used as controls. The sections were stained
      with hematoxylin-eosin, Fontana-Masson, antibodies to NKI/beteb, MART-1 (Melanoma
      Antigen Recognized by T cells), S-100 protein and androgen receptor (AR).
      RESULTS: Histopathologic features of BN showed frequent acanthosis,
      papillomatosis, keratotic plugging, irregular rete ridge elongation and
      flattening in the epidermis. Especially, the shape of the rete ridges in BN had a
      relatively characteristic appearance, which was the fusion of more than two
      adjacent rete ridges. Melanocyte counts were significantly increased in BN skin.
      The extent of AR expression was significantly higher in the epidermis of BN.
      CONCLUSIONS: Our study indicates that there may be an association between AR and
      BN, but additional studies will be required to evaluate this further.

PMID- 18616761
TI  - Atrophoderma of Pasini and Pierini: a clinical and histopathological study.
AB  - BACKGROUND: Idiopathic atrophoderma of Pasini and Pierini (IAPP) usually
      manifests as one or multiple depressed and hyperpigmented patches, with a
      predilection to the trunk. No diagnostic changes are usually seen on histology.
      Elastic stains often reveal no abnormalities. OBJECTIVE: To review our cases of
      IAPP, describe their clinical and histological findings and compare them with the
      literature. METHODS: Retrospective review of IAPP cases who presented to our
      institution between 1994 and 2006. RESULTS: From a total of 16 patients, only 19%
      displayed hyperpigmented lesions, while 81% had either hypopigmented (9/16) or
      skin-colored (4/16) lesions. The sites predominantly affected were the lower
      extremities (62.5%), followed by the upper extremities and trunk. Only in one
      patient was IAPP co-existent with morphea. Histology revealed no diagnostic
      abnormalities; however, elastic stains showed a spectrum of changes ranging from
      normal to severe diminution and fragmentation of elastic fiber network.
      CONCLUSIONS: Our study shows several new aspects of IAPP. Clinically, the lesions
      were most commonly hypopigmented and involved predominantly the extremities.
      Histologically, IAPP exhibited a spectrum of alterations in elastic fibers. The
      most prevalent form of IAPP in our country seems to be unassociated with morphea.

PMID- 18616762
TI  - Large CD30-positive cells in benign, atypical lymphoid infiltrates of the skin.
AB  - BACKGROUND: Cutaneous infectious and inflammatory diseases may contain a
      significant number of CD30-positive cells, thus mimicking lymphomatoid papulosis
      (LyP) or anaplastic large cell lymphoma. METHODS: We reviewed our cases of non
      neoplastic skin conditions with large, CD30-positive cells and searched the
      literature for similar cases. RESULTS: A total of 28 cases were included in the
      study: Milker's nodule (n = 8), Herpes simplex virus infection (n = 7),
      lymphomatoid drug reaction (n = 3), molluscum contagiosum (n = 3), nodular
      scabies (n = 2), leishmaniasis (n = 1), syphilis (n = 1), pernio (n = 1),
      ruptured infundibular cyst (n = 1) and pseudolymphoma in a scar (n = 1). CD30
      positive cells were often arranged in clusters and revealed both Golgi and
      membrane positivity, similar to what was observed in LyP and CD30+ anaplastic
      large T-cell lymphoma. CONCLUSIONS: Analysis of our data and of those published
      in the literature shows that viruses and drugs are the most common cause for
      occurrence of large CD30-positive cells in cutaneous pseudolymphomatous
      infiltrates. Arrangement of these large, CD30-positive cells in small clusters is
      not unique to cutaneous CD30-positive lymphomas, and in many cases a precise
      diagnosis can be made only upon accurate clinicopathological correlation or using
      ancillary methods such as polymerase chain reaction analysis for viral DNA.

PMID- 18616763
TI  - Evaluation of skin biopsies for fungal infections: role of routine fungal
      staining.
AB  - BACKGROUND: The diagnosis of cutaneous fungal infection is usually made on
      clinical examination of the lesion and direct microscopic examination of skin
      scrapings with potassium hydroxide. Histopathological examination is rarely
      required to confirm dermatophytic infections. There is often a discord between
      the clinical and histopathological findings and many times clinical appearance
      can have a poor histopathological correlation. METHODS: This retrospective study
      was carried out on all skin biopsies received in a period of 1 year. The clinical
      details of all cases were retrieved and slides were reviewed. Routine fungal
      staining periodic acid-Schiff (PAS) stain was performed in all cases. RESULTS: Of
      403 skin biopsies received in 1 year, material for further staining was available
      in 338. On re-examining the slides stained with PAS stain, fungi were identified
      in 34 cases (10%), of which fungal infection had been suspected clinically in
      five cases. CONCLUSIONS: Use of routine stains like PAS can help to reach a
      correct diagnosis and initiate appropriate treatment. Fungal staining should be
      done in skin biopsies with non-specific clinical details and microscopic findings
      for best patient management.

PMID- 18616764
TI  - Granuloma annulare--a manifestation of infection with Borrelia?
AB  - BACKGROUND: Among the theories of origin of granuloma annulare (GA) are those of
      infection. Reports gave raise to the assumption that there is evidence for
      Borrelia as the causing agent. METHODS: To assess the evidence for infection with
      Borrelia in GA, tissue sections were stained with a polyclonal Borrelia antibody.
      With focus-floating microscopy (FFM), slides were scanned at a 200- to 400-fold
      magnification. Part of the material was also investigated with a Borrelia
      specific polymerase chain reaction (PCR). RESULTS: A total of 157 biopsies of GA
      have been investigated. Using FFM, Borrelia were detected in 127 cases of GA
      (80.9%). Borrelia were more prominent in localized (85.2%) than in diffuse GA
      (62.1%). In 27 cases of GA analysed by PCR, Borrelia-specific DNA could be
      detected in only one case (3.7%), but was positive in 21 cases by FFM (77.8%).
      About 93.3% of 15 control cases of borreliosis were positive with FFM and 46.7%
      with PCR, while all controls other than borreliosis remained negative for
      spirochetes. CONCLUSION: FFM is a reliable method to show Borrelia in tissue
      sections of GA, which is more sensitive than PCR. This underlines the possibility
      that Borrelia are involved specifically in the aetiology and pathogenesis of GA.

PMID- 18616765
TI  - Distribution of Malassezia species in patients with psoriasis and healthy
      individuals in Tehran, Iran.
AB  - BACKGROUND: Psoriasis is a non-contagious disorder that affects the skin as red
      scaly patches. Although the role of Malassezia species in the pathogenesis of
      psoriasis is still not fully understood, it is thought that these lipophilic
      yeasts might be a trigger factor in the exacerbation of psoriatic lesions.
      METHODS: Using culture in a specific medium followed by the polymerase chain
      reaction-restriction fragment length polymorphism method, the presence of
      Malassezia species in the skin of 110 patients with psoriasis was compared with
      that in a control group of 123 healthy patients. RESULTS: The recovery rate of
      Malassezia species from the skin of patients with psoriasis was significantly
      lower than that in the controls. In both psoriatic and healthy skin, Malassezia
      globosa was isolated as the predominant species. In psoriatic patients, the rate
      of colonization of Malassezia furfur and Malassezia restricta was almost twice
      that in the controls, whereas M. globosa was isolated more frequently from
      healthy individuals than from patients. CONCLUSIONS: Considering the higher
      lipase activity secretion by M. furfur in comparison with other Malassezia
      species, the enzymatic release of arachidonic acid and its metabolites by M.
      furfur may exacerbate the inflammatory and hyperproliferative changes observed in
      psoriasis.

PMID- 18616766
TI  - Follicular streamers (stelae) in scarring and non-scarring alopecia.
AB  - BACKGROUND: Follicular streamers are residual fibrovascular tracts representing
      the impermanent lower third of the hair follicle below the bulge region.
      Streamers are generally not counted in transverse alopecia samples as they may
      represent catagen/telogen (CT) follicles and vellus-like (VL) follicles, or be
      mistaken as follicular scars. DESIGN: We evaluated 22 non-scarring alopecia
      cases, including alopecia areata (AA) and androgenetic alopecia (AGA), and 22
      scarring alopecia cases, including follicular degeneration syndrome (FDS)/central
      centrifugal cicatricial alopecia and other scarring alopecia (OSA) disorders. We
      counted terminal follicular streamers found at a deep dermal level (L2) and
      followed them into a mid-dermal level at the central follicular unit (FU) to
      determine their precise derivation. RESULTS: We found streamers in 8/9 AA, 11/13
      AGA, 6/12 FDS and 3/10 OSA cases. We counted a total of 74 streamers at L2,
      including 61 in non-scarring alopecia cases (p < 0.001). At the more superficial
      FU level, 72% of streamers corresponded to CT follicles, 25% to VL follicles and
      3% to follicular scars. CONCLUSIONS: Follicular streamers are found predominantly
      in non-scarring alopecia cases. Streamers found at deep dermal or subcutaneous
      levels should be followed and identified at the FU level in order to obtain
      accurate follicular counts and follicular ratios needed for non-scarring alopecia
      diagnosis.

PMID- 18616767
TI  - Accuracy of clinical diagnosis of skin lesions.
AB  - BACKGROUND: Skin cancer is an increasing problem in fair-skinned populations
      worldwide. It is important that doctors are able to diagnose skin lesions
      accurately. OBJECTIVES: To compare the clinical with the histological diagnosis
      of excised skin lesions from a set of epidemiological data. We analysed
      diagnostic accuracy stratified by histological subtype and body site and examined
      the histological nature of misclassified diagnosis. METHODS: All excised and
      histologically confirmed skin cancers in Townsville/Thuringowa, Australia from
      December 1996 to October 1999 were recorded. Positive predictive values (PPVs)
      and sensitivities were calculated for the clinical diagnoses and stratified by
      histological subtype and body site. RESULTS: Skin excisions in 8694 patients were
      examined. PPVs for the clinical diagnoses were: basal cell carcinoma (BCC) 72.7%;
      squamous cell carcinoma (SCC) 49.4%; cutaneous melanoma (CM) 33.3%. Sensitivities
      for the clinical diagnosis were: BCC 63.9%; SCC 41.1%; CM 33.8%. For BCC, PPVs
      and sensitivities were higher for the trunk, the shoulders and the face and lower
      for the extremities. The reverse pattern was seen for SCCs. CONCLUSIONS:
      Diagnostic accuracy was highest for BCC, the most prevalent lesion. Most
      excisions were correctly diagnosed or resulted in the removal of malignant
      lesions. With nonmelanocytic lesions, doctors tended to misclassify benign
      lesions as malignant, but were less likely to do the reverse. Although a small
      number of clinically diagnosed common naevi subsequently proved to be melanoma
      (6.3%), a higher proportion of all melanomas had been classified as common naevi
      (20.9%). Accuracy of diagnosis was dependent on body site.

PMID- 18616768
TI  - A cautionary tale.

PMID- 18616769
TI  - Dermoscopy compared with naked eye examination for the diagnosis of primary
      melanoma: a meta-analysis of studies performed in a clinical setting.
AB  - BACKGROUND: Dermoscopy is a noninvasive technique that enables the clinician to
      perform direct microscopic examination of diagnostic features, not seen by the
      naked eye, in pigmented skin lesions. Diagnostic accuracy of dermoscopy has
      previously been assessed in meta-analyses including studies performed in
      experimental and clinical settings. OBJECTIVES: To assess the diagnostic accuracy
      of dermoscopy for the diagnosis of melanoma compared with naked eye examination
      by performing a meta-analysis exclusively on studies performed in a clinical
      setting. METHODS: We searched for publications from 1987 to January 2008 and
      found nine eligible studies. The selected studies compare diagnostic accuracy of
      dermoscopy with naked eye examination using a valid reference test on consecutive
      patients with a defined clinical presentation, performed in a clinical setting.
      Hierarchical summary receiver operator curve analysis was used to estimate the
      relative diagnostic accuracy for clinical examination with, and without, the use
      of dermoscopy. RESULTS: We found the relative diagnostic odds ratio for melanoma,
      for dermoscopy compared with naked eye examination, to be 15.6 [95% confidence
      interval (CI) 2.9-83.7, P = 0.016]; removal of two outlier studies changed this
      to 9.0 (95% CI 1.5-54.6, P = 0.03). CONCLUSIONS: Dermoscopy is more accurate than
      naked eye examination for the diagnosis of cutaneous melanoma in suspicious skin
      lesions when performed in the clinical setting.

PMID- 18616770
TI  - Caspase-1 activity of stratum corneum and serum interleukin-18 level are
      increased in patients with Netherton syndrome.

PMID- 18616771
TI  - Rapid diagnosis of monilethrix using dermoscopy.

PMID- 18616772
TI  - A multicentre randomized controlled trial of ion-exchange water softeners for the
      treatment of eczema in children: protocol for the Softened Water Eczema Trial
      (SWET) (ISRCTN: 71423189).
AB  - BACKGROUND: There is epidemiological evidence linking increased water hardness
      with increased eczema prevalence. A number of plausible mechanisms can be
      forwarded to suggest why hard water could exacerbate eczema. The most likely
      explanation is increased soap usage in hard water areas, the deposits of which
      can cause skin irritation in individuals with eczema. OBJECTIVES: To assess the
      cost and cost-effectiveness of ion-exchange water softeners for the treatment of
      eczema in children. PATIENTS/METHODS: Three hundred and ten children aged 6
      months to 16 years, with moderate to severe eczema. The children must live in
      hard water areas (>or= 200 mg L(-1) of calcium carbonate) and have a home that is
      suitable for the installation of a water softener. This is a single-blind,
      parallel-group, randomized controlled trial of 12 weeks duration followed by a 4
      week cross-over period. RESULTS/ANALYSIS PLAN: PRIMARY OUTCOME: difference in the
      mean change in disease severity (Six Area, Six Sign Atopic Dermatitis score) at
      12 weeks compared with baseline. SECONDARY OUTCOMES: (i) proportion of time spent
      moving during the night; (ii) self-reported global changes in eczema severity;
      (iii) amount of topical treatment used; (iv) Patient Oriented Eczema Measure; (v)
      number of totally controlled and well controlled weeks; (vi) impact on health
      related quality of life for the child (EQ-5D) and the family (Dermatitis Family
      Impact questionnaire); and (vii) cost-effectiveness. It is planned that
      recruitment will be completed by the end of 2008 and results will be available
      towards the end of 2009.

PMID- 18616773
TI  - Successful treatment of field cancerization of the scalp by surface mould
      brachytherapy.

PMID- 18616774
TI  - The autoimmune regulator gene (AIRE) is strongly associated with vitiligo.
AB  - BACKGROUND: Vitiligo is an autoimmune disorder that occurs with greatly increased
      frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune
      regulator (AIRE) gene on chromosome 21q22.3. We have previously detected an
      association between alopecia areata and single nucleotide polymorphisms (SNPs) in
      the AIRE gene. OBJECTIVES: To report the findings of an extended study including
      haplotype analysis on six AIRE polymorphisms (AIRE C-103T, C4144G, T5238C,
      G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease.
      METHODS: A case-control analysis was performed. RESULTS: Results showed a strong
      association between AIRE 7215C and vitiligo [P = 1.36 x 10(-5), odds ratio (OR)
      3.12, 95% confidence interval (CI) 1.87-5.46]. We found no significant
      association with the other polymorphisms individually. However, haplotype
      analysis revealed that the AIRE haplotype CCTGCC showed a highly significant
      association with vitiligo (P = 4.14 x 10(-4), OR 3.00, 95% CI 1.70-5.28). To
      select the most informative minimal haplotypes, we tagged the polymorphisms using
      SNP tag software. Using AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, the
      haplotype AIRE CGCC was associated with vitiligo (P = 0.003, OR 2.49, 95% CI 1.45
      4.26). CONCLUSIONS: The link between vitiligo and AIRE raises the possibility
      that defective skin peripheral antigen selection in the thymus is involved in the
      changes that result in melanocyte destruction in this disorder.

PMID- 18616775
TI  - A de novo missense mutation in the keratin 13 gene in oral white sponge naevus.

PMID- 18616776
TI  - Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes
      and restore the Th1/Th2 balance in patients with metastatic melanoma.
AB  - BACKGROUND: Patients with metastatic skin disease in malignant melanoma are
      difficult to treat, with unresectable lesions proving the biggest challenge. We
      have recently published data showing a significant clinical response in patients
      with multiple in-transit melanoma metastases treated with a combination of
      topical imiquimod and intralesional interleukin (IL)-2. Here we report the
      results of immunological analysis with the aim of highlighting correlations with
      our clinical findings. OBJECTIVES: To investigate the systemic effects of our
      localized combination treatment in patients with accessible metastases of
      melanoma, and to correlate this with their clinical responses. METHODS: The
      peripheral blood mononuclear cells of patients were collected at various time
      points throughout the treatment. Using antibodies to T-cell subsets we measured
      the changes in cell populations, and along with polyclonal stimulation, changes
      in cytokine production from these cells over a treatment course. RESULTS: We
      report an increase in the mean CD4/CD8 ratio from 2.78 to 3.54 with treatment (P
      < 0.01), and a rise in the percentage of CD25+ cells in the CD4+ population from
      14.52% to 38.56%. Furthermore, staining with activation and T-regulatory markers
      showed that the majority of this population is activated T cells. Cytokine
      analysis on polyclonally stimulated peripheral blood mononuclear cells showed an
      increase in the ability of cells to produce interferon (IFN)-gamma over the
      treatment course, with an initial rise in the IFN-gamma/IL-5 ratio in five of six
      patients. CONCLUSIONS: The results of this study provide evidence that, in the
      majority of patients with in-transit metastases of melanoma, therapy with a
      combination of topical imiquimod and intralesional IL-2 induces a systemic
      immunological effect by reversing some of changes noted in patients with
      malignant disease.

PMID- 18616777
TI  - Dynamics of pigmentation induction by repeated ultraviolet exposures: dose, dose
      interval and ultraviolet spectrum dependence.
AB  - BACKGROUND: The dynamics of ultraviolet (UV)-induced melanogenesis have been well
      characterized for single UV exposures. However, our knowledge of the effects of
      repeated UV exposures on the development of new pigmentation is limited.
      OBJECTIVES: To characterize the dynamics and dose dependence of pigmentation
      induction by repeated UV exposures using two different UV sources. METHODS: A
      total of 40 healthy subjects participated in the study: 21 were exposed to a 5%
      UVB/95% UVA source and 19 were exposed to a 2% UVB/98% UVA source. Skin
      phototypes 2-3 were represented. Subjects were exposed one to three times per
      week. The minimal erythemal dose and minimal melanogenic dose of all subjects
      were determined, and both visual and instrumental observations of the development
      of pigmentation and erythema were recorded. RESULTS: Dark-brown pigmentation
      could be produced by a cumulative UV dose of 4200 J m(-2) given as 10 exposures
      over 5 weeks. However, comparable pigmentation could also be induced by a
      cumulative dose of 2900 J m(-2) given as eight exposures over 4 weeks. The lowest
      cumulative dose of 1900 J m(-2) given over 4 weeks produced moderate
      pigmentation. The 2% UVB source led to earlier and darker pigmentation than the
      5% UVB source did for equally erythemogenic doses. CONCLUSIONS: These
      observations show that the dynamics of melanogenesis induced by repeated
      exposures depends on UV dose, dose interval and emission spectrum. They also
      indicate that increasing the UV dose above a certain level of cumulative exposure
      does not significantly increase the level of UV-induced pigmentation.

PMID- 18616778
TI  - Incidence of risk factors for myocardial infarction and other vascular diseases
      in patients with psoriasis.
AB  - BACKGROUND: Recent cross-sectional studies reported a higher prevalence of
      diabetes and other risk factors for cardiovascular disease in patients with
      psoriasis than in the general population. OBJECTIVES: To estimate the cumulative
      incidences of risk factors for myocardial infarction and other vascular diseases
      after a first recorded diagnosis of psoriasis and the hazard ratio (HR) for these
      conditions in patients with psoriasis compared with the general population.
      METHODS: We used the General Practice Research Database to conduct a cohort study
      of 44,164 patients with a first-time diagnosis of psoriasis and 219,784
      nonpsoriasis comparison subjects psoriasis-matched on age, sex and index date.
      RESULTS: HRs were increased among patients with psoriasis vs. the comparison
      cohort for incident diabetes [HR 1.33; 95% confidence interval (CI) 1.25-1.42],
      hypertension (HR 1.09; 95% CI 1.05-1.14), obesity (HR 1.18; 95% CI 1.14-1.23) and
      hyperlipidaemia (HR 1.17; 95% CI 1.11-1.23). Patients with psoriasis also had
      higher risks of incident myocardial infarction (HR 1.21; 95% CI 1.10-1.32),
      angina (HR 1.20; 95% CI 1.12-1.29), atherosclerosis (HR 1.28; 95% CI 1.10-1.48),
      peripheral vascular disease (HR 1.29; 95% CI 1.13-1.47) and stroke (HR 1.12; 95%
      CI 1.00-1.25). CONCLUSIONS: Risk factors for cardiovascular disease as well as
      myocardial infarction and other vascular diseases occur with higher incidence in
      patients with psoriasis than in the general population. Further work is needed to
      investigate whether these associations involve causal factors related to
      psoriasis or its treatment.

PMID- 18616779
TI  - Alopecia-mental retardation syndrome: clinical and molecular characterization of
      four patients.

PMID- 18616780
TI  - A randomized controlled trial of the efficacy and safety of a fixed triple
      combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%)
      compared with hydroquinone 4% cream in Asian patients with moderate to severe
      melasma.
AB  - BACKGROUND: Melasma is an acquired, chronic hypermelanosis for which therapy
      remains a challenge. OBJECTIVES: To compare the efficacy and safety of a triple
      combination [TC: fluocinolone acetonide 0.01%, hydroquinone (HQ) 4%, tretinoin
      0.05%] vs. HQ 4% after 8 weeks of treatment of moderate to severe facial melasma
      in Asian patients. METHODS: This was a multicentre, randomized, controlled,
      investigator-blinded, parallel comparison study. East and South-East Asian
      patients aged 18 years or older, with a clinical diagnosis of moderate to severe
      melasma, were enrolled in this study. Patients were enrolled at baseline and
      treated daily for 8 weeks with TC cream (one application at bedtime) or HQ cream
      (twice daily). There were four study visits: at baseline and weeks 2, 4 and 8.
      The primary efficacy variable was the melasma global severity score (GSS). Other
      outcome measures included Melasma Area and Severity Index, global improvement and
      patient satisfaction. Safety was assessed through the reporting of adverse
      events. RESULTS: TC had superior efficacy to HQ for the primary variable: 77/120
      patients (64.2%) on TC had GSS 'none' or 'mild' at week 8 vs. 48/122 patients
      (39.4%) on HQ (P < 0.001). The secondary efficacy variables confirmed these
      results. Patient satisfaction was in favour of TC (90/127, 70.8%, vs. 64/129,
      49.6%; P = 0.005). More patients had related adverse events on TC (63/129, 48.8%)
      than on HQ (18/131, 13.7%) but most were mild and none was severe. CONCLUSIONS:
      Efficacy in Asians and patient satisfaction were superior with the fixed TC than
      with HQ 4%.

PMID- 18616781
TI  - Is there a relationship between homocysteine and vitiligo? A pilot study.
AB  - BACKGROUND: Pigmentary dilution is observed in patients with homocystinuria.
      Therefore, it is possible that an increase of local homocysteine (Hcy) interferes
      with normal melanogenesis and plays a role in the pathogenesis of vitiligo.
      Vitamin B12 and folic acid, levels of which are decreased in vitiligo, are
      important cofactors in the metabolism of Hcy. Consequently, a nutritional
      deficiency in either of these two vitamins will result in an increase in
      homocysteine in the circulation, a finding that we expect to find in vitiligo.
      OBJECTIVE: To determine the level of Hcy in the blood of patients with vitiligo
      as a first step in revealing if it has any relationship with the pathogenesis of
      vitiligo and consequently if this will have an impact on the treatment of
      vitiligo. METHODS: Twenty-six patients of both sexes with vitiligo (age range 20
      50 years, mean 31.4 +/- 8.09) and 26 age-matched healthy controls were included
      in the study. After excluding factors that may affect serum Hcy levels, blood
      samples from patients and controls were obtained for homocysteine determination
      by enzyme immunoassay. RESULTS: The mean serum level of Hcy was significantly
      higher in patients with vitiligo than in controls (21.61 +/- 13.28 vs. 13.1 +/-
      4.88 micromol L(-1); P < 0.001). The Hcy level was significantly higher in male
      patients than in female patients (28.67 +/- 15.95 vs. 15.56 +/- 6.2 micromol L(
      1); P < 0.001) and in male controls compared with female controls (15.07 +/- 4.61
      vs. 12.05 +/- 4.82 micromol L(-1); P < 0.001). The homocysteine level was related
      to the activity of vitiligo and was significantly higher in patients with
      progressive disease than in controls (25.4 +/- 14.99 vs. 13.1 +/- 4.88 micromol
      L(-1); P < 0.001). No significant difference in Hcy levels was found between
      either untreated vitiligo patients (22.77 +/- 13.36 micromol L(-1)) or patients
      receiving ultraviolet therapy (20.45 +/- 13.73 micromol L(-1)) and the total
      patient group (21.62 +/- 13.28 micromol L(-1)). CONCLUSION: An elevated
      homocysteine level may be a precipitating factor for vitiligo in predisposed
      individuals. In view of the biological role of vitamin B(12) and folic acid in
      Hcy metabolism, we present our recommendations regarding the investigation and
      treatment of this common disease.

PMID- 18616783
TI  - Measuring the effects of topical moisturizers on changes in stratum corneum
      thickness, water gradients and hydration in vivo.
AB  - BACKGROUND: Moisturizers are the most commonly used topically applied product for
      the treatment of dry skin conditions. They affect many properties and functions
      of the stratum corneum but some moisturizers have been reported to be detrimental
      to barrier function. Stratum corneum barrier function is a composite of its total
      structure and thickness but few studies have taken this into account. As a
      biosensor, the stratum corneum (SC) will change its structure in response to
      treatment and a swelling effect has been clearly demonstrated by skin hydration.
      Recently several moisturizing agents have been shown to have an effect on SC
      swelling behaviour with conflicting results. However, there is a paucity of data
      reported for measuring the effects of long-term usage of moisturizers on SC
      thickness in vivo as, until recently, traditional techniques did not have the
      resolution to measure the effects of moisturizers on nonpalmoplantar body sites.
      The development of confocal Raman spectroscopy for use in human subjects provides
      noninvasive, real-time, in vivo measurement of SC water concentration profiles
      and we have also used this state of the art equipment to measure the effect of
      the long-term use of moisturizers on SC thickness for the first time. OBJECTIVES:
      To validate the use of confocal Raman spectroscopy (CRS) to measure SC thickness
      and then use it to investigate the short- and long-term effects of moisturizers
      (one of which is known to improve SC barrier function) on SC thickness, water
      gradients and hydration. METHODS: Two studies were conducted: (i) to validate the
      use of CRS for measuring SC thickness through comparison with optical coherence
      tomography (OCT); and (ii) once validated to use CRS to measure the long-term
      effects of three commercially available moisturizers (A, B, C) on SC thickness
      and water gradients, together with total hydration, over a 3-week period (2 weeks
      of treatment and 1 week regression) and compare the spectroscopy-derived
      hydration value with instrumentally derived capacitance hydration values.
      RESULTS: (i) A strong, positive correlation in SC thickness was obtained between
      CRS and OCT (OCT-derived thickness = 0.96 x CRS-derived thickness, r(2) = 0.93; P
      <0.0001). OCT was shown, however, to have a lower resolution than CRS in
      distinguishing SC thickness on thinner nonpalmoplantar body sites. Using the CRS
      method, differences in SC thickness were readily apparent on different body sites
      (cheek 12.8 +/- 0.9 microm, volar forearm 18.0 +/- 3.9 microm, leg 22.0 +/- 6.9
      microm). (ii) Examining the effects of moisturizers in a blinded, randomized 3
      week study in human volunteers (n = 14) demonstrated that only one commercially
      available formulation (A) changed SC water gradients, thickness and hydration as
      measured by CRS. These hydration data did not directly correlate with capacitance
      hydration values. CONCLUSIONS: (i) In vivo CRS was validated as a technique to
      measure SC thickness on both palmoplantar and, particularly, on nonpalmoplantar
      skin sites. (ii) Moisturizers improve skin moisturization but in this study only
      formulation A improved SC thickness, water gradients and hydration as measured by
      CRS. We hypothesize that this was due to compositional differences between the
      products. We believe that niacinamide (nicotinamide, vitamin B(3)) is probably
      contributing significantly to this effect, as it has been proven to increase
      epidermal lipogenesis and SC barrier function in other studies. These results
      show that by using CRS, we were able for the first time to determine the effect
      of moisturizer on multiple SC barrier endpoints including SC thickness, and water
      content as a function of depth and total SC water content.

PMID- 18616782
TI  - Comparison of the reliability and validity of outcome instruments for cutaneous
      dermatomyositis.
AB  - BACKGROUND: Reliable and validated measures of skin disease severity are needed
      for cutaneous dermatomyositis (DM). Cutaneous Dermatomyositis Disease Area and
      Severity Index (CDASI), Dermatomyositis Skin Severity Index (DSSI) and Cutaneous
      Assessment Tool (CAT) skin indices have been developed as outcome instruments.
      OBJECTIVES: We sought to demonstrate reliability and validity of the CDASI, and
      to compare the CDASI with other potential tools for use in measuring disease
      severity in cutaneous dermatomyositis. PATIENTS AND METHODS: CDASI has four
      activity and two damage measures, with scores from 0 to 148. DSSI assesses
      activity based on body surface area and severity on a scale of 0-72. CAT uses 21
      activity and damage items, for a range of 0-175 for activity and 0-33 for damage.
      Ten dermatologists used the instruments to score the same 12-16 patients in one
      session. Global validation measures were administered to physicians and patients.
      RESULTS: Global validation measures correlated with the three outcome instruments
      (P < 0.0001). CAT displayed lower inter- and intrarater reliability relative to
      the CDASI. All scales correlate better with physician than patient global skin
      measures. CONCLUSIONS: It appears that the CDASI may be a useful outcome measure
      for studies of cutaneous DM. Further testing to compare responsiveness of all
      three measures is necessary.

PMID- 18616784
TI  - Mortality in Danish patients with nonmelanoma skin cancer, 1978-2001.
AB  - BACKGROUND: Nonmelanoma skin cancer (NMSC) is a growing public health problem
      among Caucasians, thus mortality data that may provide insight into the clinical
      course and foster our understanding of NMSC are important. OBJECTIVES: We
      examined total and cause-specific mortality among patients with NMSC registered
      in the Danish Cancer Registry from 1978 to 2001. METHODS: A total of 82 837
      patients with basal cell carcinoma (BCC) and 13 453 patients with squamous cell
      carcinoma (SCC) were followed through the National Death Registry for specific
      causes of death. Standardized mortality ratios (SMRs) were computed based on
      mortality rates in the general population. RESULTS: Among patients with BCC, we
      found a slightly reduced total mortality [SMR 0.97, 95% confidence interval (CI)
      0.96-0.98] with decreased SMRs seen for chronic obstructive pulmonary disease
      (COPD), cardiovascular disease (CVD) and diabetes mellitus. The SMR for suicide
      was increased. Among patients with SCC, we found an increased total mortality
      (SMR 1.30, 95% CI 1.26-1.33) due primarily to excess deaths from cancers, COPD,
      CVD and infectious diseases. CONCLUSIONS: We found markedly different mortality
      patterns among patients with BCC and those with SCC, suggesting important
      differences in the clinical course of these patients.

PMID- 18616785
TI  - The risk of cardiomyopathy in inherited epidermolysis bullosa.
AB  - BACKGROUND: Case reports have suggested that cardiomyopathy may be a complication
      of recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVE: To determine the
      risk of congestive heart failure (CHF) or cardiomyopathy in each major EB
      subtype. METHODS: These data represent systematic case findings and data
      collection performed throughout the continental United States from 1986 through
      2002, by the National Epidermolysis Bullosa Registry. Study design is cross
      sectional (n = 3280) with a nested randomly sampled longitudinal subcohort (n =
      450). Frequencies of CHF and cardiomyopathy were determined by patient self
      reporting, medical histories and review of medical records. In those who died,
      death certificates were reviewed and histories obtained from surviving family.
      Cumulative risks were stratified by cause and EB subtype. RESULTS: Cardiomyopathy
      was reported as early as within the first year of life. In patients having no
      other known risk factors for CHF or cardiomyopathy, the highest risk of
      cardiomyopathy was seen among patients with Hallopeau-Siemens RDEB (RDEB-HS),
      with a cumulative risk of 4.51% on or after age 20 years. The cumulative risk of
      cardiomyopathy was only 1.14% and 0.40% in non-Herlitz junctional EB (JEB) and
      non-Hallopeau-Siemens RDEB, respectively, and was not observed in any other EB
      subtype. When patients with coexistent chronic renal failure were included, the
      cumulative risk for RDEB-HS rose to 18.86% by age 35 years. About 30% of our
      patients affected with RDEB-HS died of CHF or cardiomyopathy, even those with no
      other known risk factors. CONCLUSIONS: CHF and cardiomyopathy are uncommon
      complications in both major RDEB subtypes and non-Herlitz JEB, and may be fatal.

PMID- 18616786
TI  - Transforming growth factor-beta/Smad3 signalling regulates inflammatory responses
      in a murine model of contact hypersensitivity.
AB  - BACKGROUND: Transforming growth factor (TGF)-beta is an important modulator of
      immune functions and cellular responses, such as differentiation, proliferation,
      migration and apoptosis. The Smad proteins, which are intracellular TGF-beta
      signal transducers, mediate most actions of TGF-beta. OBJECTIVES: This study
      examines the role of Smad3 in a murine model of contact hypersensitivity (CHS).
      METHODS: The CHS response to oxazolone was studied in Smad3-deficient mice. The
      ear swelling response was measured and skin biopsies from oxazolone-sensitized
      skin areas were obtained for RNA isolation, immunohistochemical analyses and
      histology. Ear draining lymph nodes were collected for RNA isolation and
      proliferation tests. Quantitative real-time polymerase chain reaction was used to
      quantify mRNA expression of cytokines, chemokines and transcription factors.
      Results The expression of proinflammatory [interleukin (IL)-1beta, tumour
      necrosis factor-alpha, IL-6], Th2 (IL-4) and Th17 type cytokines (IL-17), as well
      as regulatory components (TGF-beta, Foxp3) increased significantly at the mRNA
      level in the skin of oxazolone-treated Smad3-/- mice when compared with wild-type
      controls. The expression of the Th1 type cytokine IFN-gamma and the chemokines
      CXCL9 and CXCL10 was, however, unaffected by the lack of Smad3. The number of
      neutrophils and expression of the chemokines CCL3 and CXCL5, which are both
      involved in neutrophil recruitment, were increased in mice lacking Smad3. Also
      Th2 type chemokines CCL24, CCL3 and CXCL5 were increased in the skin of Smad3-/-
      mice compared with wild-type mice. In the lymph nodes, mRNA of IL-1beta and IL
      17, but not IL-4, TGF-beta or Foxp3, was increased in Smad3-/- mice during the
      CHS response. CONCLUSIONS: The lack of intact TGF-beta signalling via Smad3
      results in an increased proinflammatory, Th2 and Th17 type response in the skin,
      as well as increased expression of regulatory elements such as TGF-beta and
      Foxp3. Understanding the role of Smad3 in the CHS response may offer treatment
      and prevention strategies in this often disabling disease.

PMID- 18616787
TI  - Lower serum dehydroepiandrosterone sulphate concentration in chronic idiopathic
      urticaria: a secondary transient phenomenon?

PMID- 18616788
TI  - Defects in DNA mismatch repair do not account for early-onset basal cell
      carcinoma.

PMID- 18616789
TI  - Molecular and biochemical testing in stage III melanoma: multimarker reverse
      transcriptase-polymerase chain reaction assay of lymph fluid after lymph node
      dissection and preoperative serum lactate dehydrogenase level.
AB  - BACKGROUND: There is a need for biomarkers to identify patients at risk for
      disease progression after resection of melanoma regional lymph node metastasis.
      OBJECTIVES: This study assessed the prognostic value of multimarker reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay in lymphatic drainage (LY)
      after lymph node dissection (LND) and of preoperative serum lactate dehydrogenase
      (LDH) levels in American Joint Committee on Cancer (AJCC) stage III melanoma
      patients. METHODS: We collected 24-h LY from 255 stage III melanoma patients
      after radical LND [114, completion LND after positive sentinel node biopsy
      (CLND); 141, therapeutic LND for clinically/cytologically detected regional nodal
      metastases (TLND)]. For detection of melanoma cells, RT-PCR assays with primers
      specific for tyrosinase, MART1 (MelanA) and uMAGE mRNA were conducted. The LY
      sample was deemed positive if at least one marker was detected. In 244 patients,
      the preoperative serum LDH level was available. Median follow-up time was 25
      months (range 5-60). RESULTS: The LY multimarker RT-PCR assay results were
      positive in 82 of 255 patients (32%). A significantly higher rate of melanoma
      recurrence was observed in patients with positive LY multimarker RT-PCR results
      (P = 0.01). Significant relationships were observed between positive LY
      multimarker RT-PCR results and shorter 3-year overall survival (OS) and disease
      free survival (DFS), both in univariate and multivariate analyses (P = 0.007).
      Preoperative serum LDH level was increased in 79 of 244 patients (32%) [40.5% in
      TLND group and 23.0% in CLND group (P = 0.003)]. There were significant
      differences in OS between patients with normal and high preoperative LDH levels
      (P = 0.007), and these differences were seen mainly in patients in the TLND
      group. CONCLUSIONS: The multimarker RT-PCR assay detected melanoma cells in
      approximately 32% of LY after LND, which correlated significantly with early
      melanoma recurrence and shorter survival. Increased pre-LND serum LDH level had
      an additional negative impact on OS of melanoma patients with palpable nodal
      metastases after TLND.

PMID- 18616790
TI  - Platelet lysate stimulates wound repair of HaCaT keratinocytes.
AB  - BACKGROUND: Platelets play a pivotal role in wound healing. Their beneficial
      effect is attributed to the release of bioactive substances, although the
      involved mechanisms are mostly unknown. OBJECTIVES: To investigate mechanisms
      underlying platelet-induced wound healing using HaCaT keratinocytes, representing
      an in vitro model of proliferating and migrating keratinocytes. METHODS: Cells
      were exposed to platelet lysate (PL) purified from whole blood samples. Cell
      metabolism and proliferation were assessed using MTS and crystal violet assays,
      respectively, wound healing was assessed by scratch wound assay and cell
      migration by transwell assay. Extracellular signal-regulated kinase (ERK) 1/2 and
      p38 activations were studied using Western immunoblotting and intracellular
      Ca(2+) dynamics by confocal imaging. RESULTS: Wound closure rates showed a
      significant increase at 6 and 24 h in cells exposed to nontoxic 20% PL. The cell
      migration assay showed a strong chemotactic effect toward PL. The intracellular
      Ca(2+) chelator BAPTA-AM induced 100% inhibition of the PL effect on wound
      closure rate, while among the kinase inhibitors, SB203580 exerted about 50%
      inhibition, and PD98059, wortmannin and LY294002 about 30% inhibition. SB203580
      and BAPTA-AM induced 100% inhibition of the PL effect on cell migration, PD98059
      about 50% inhibition, and wortmannin and LY294002 no significant inhibition.
      Confocal imaging allowed detection of a sustained Ca(2+) transient in PL-treated
      cells, while Western blot showed a more rapid activation of p38 than of ERK1/2.
      CONCLUSIONS: Data indicate that PL increases wound healing rate by stimulating
      keratinocyte migration through a calcium- and p38-dependent mechanism. ERK1/2 and
      phosphoinositide-3 kinase seem to play minor roles.

PMID- 18616791
TI  - Knowledge, attitudes and use of the guidelines for the treatment of moderate to
      severe plaque psoriasis among Dutch dermatologists.
AB  - BACKGROUND: In 2003, the Dutch psoriasis guidelines were among the first evidence
      based medicine guidelines in dermatology. Although pivotal, the implementation of
      dermatological guidelines has not been assessed. OBJECTIVES: To evaluate various
      aspects that affect implementation of clinical guidelines such as knowledge,
      attitudes and practices among dermatologists. METHODS: A cross-sectional
      anonymous postal survey was conducted among all Dutch dermatologists. In addition
      to questions about knowledge and practices, 24 items assessed guidelines
      attitudes. Factor analysis was applied to merge these items into attitudinal
      scales and multiple linear regression was used to identify predictors for these
      scales. RESULTS: Of the 353 dermatologists, 161 (46%) completed the
      questionnaire. Almost all respondents were aware of the guidelines and 60%
      reported to have a decent knowledge of their content. Factor analysis retained 22
      items divided into three scales: usefulness and content, barriers, and
      reliability. Apart from some disagreement on the user-friendliness and
      communication facilitating properties, the dermatologists' attitudes were
      generally positive. A larger volume of patients with psoriasis was associated
      with more frequent use of the guidelines [adjusted odds ratio (OR) = 2.42; 95%
      confidence interval (CI) 1.02-5.72]. Good familiarity predicted a more positive
      attitude towards the guidelines' usefulness and content (P < 0.001), perceived
      barriers (P < 0.001), and more frequent use in practice (adjusted OR = 8.38; 95%
      CI 3.08-22.81). CONCLUSIONS: Dutch dermatologists seem to know and appreciate
      their psoriasis guidelines and use them more often when they have a larger
      psoriasis population. Enhancing the familiarity of the guidelines among users may
      result in a more positive attitude towards them and a higher frequency of use.

PMID- 18616792
TI  - Tiling array-CGH for the assessment of genomic similarities among synchronous
      unilateral and bilateral invasive breast cancer tumor pairs.
AB  - BACKGROUND: Today, no objective criteria exist to differentiate between
      individual primary tumors and intra- or intermammary dissemination respectively,
      in patients diagnosed with two or more synchronous breast cancers. To elucidate
      whether these tumors most likely arise through clonal expansion, or whether they
      represent individual primary tumors is of tumor biological interest and may have
      clinical implications. In this respect, high resolution genomic profiling may
      provide a more reliable approach than conventional histopathological and tumor
      biological factors. METHODS: 32 K tiling microarray-based comparative genomic
      hybridization (aCGH) was used to explore the genomic similarities among
      synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was
      compared with histopathological and tumor biological parameters. RESULTS: Based
      on global copy number profiles and unsupervised hierarchical clustering, five of
      ten (p = 1.9 x 10-5) unilateral tumor pairs displayed similar genomic profiles
      within the pair, while only one of eight bilateral tumor pairs (p = 0.29)
      displayed pair-wise genomic similarities. DNA index, histological type and
      presence of vessel invasion correlated with the genomic analyses. CONCLUSION:
      Synchronous unilateral tumor pairs are often genomically similar, while
      synchronous bilateral tumors most often represent individual primary tumors.
      However, two independent unilateral primary tumors can develop synchronously and
      contralateral tumor spread can occur. The presence of an intraductal component is
      not informative when establishing the independence of two tumors, while vessel
      invasion, the presence of which was found in clustering tumor pairs but not in
      tumor pairs that did not cluster together, supports the clustering outcome. Our
      data suggest that genomically similar unilateral tumor pairs may represent a more
      aggressive disease that requires the addition of more severe treatment
      modalities, and underscores the importance of evaluating the clonality of
      multiple tumors for optimal patient management. In summary, our findings
      demonstrate the importance of evaluating the properties of both tumors in order
      to determine the most optimal patient management.

PMID- 18616793
TI  - Genetic heterogeneity of L-Zagreb mumps virus vaccine strain.
AB  - BACKGROUND: The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385,
      Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous
      analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous.
      RESULTS: We identified the heterogeneity of L-Zagreb throughout the entire
      genome. Two major variants were defined: variant A being identical to the
      consensus sequence of viral seeds and vaccine(s) and variant B which differs from
      variant A in three nucleotide positions. The difference between viral variants in
      L-Zagreb strain is insufficient for distinct viral strains to be defined. We
      demonstrated that proportion of variants in L-Zagreb viral population depends on
      cell substrate used for viral replication in vitro and in vivo. CONCLUSION: L
      Zagreb strain should be considered as a single strain composed of at least two
      variant viral genomes.

PMID- 18616794
TI  - Alternative medicines for AIDS in resource-poor settings: insights from
      exploratory anthropological studies in Asia and Africa.
AB  - The emergence of alternative medicines for AIDS in Asia and Africa was discussed
      at a satellite symposium and the parallel session on alternative and traditional
      treatments of the AIDSImpact meeting, held in Marseille, in July 2007. These
      medicines are heterogeneous, both in their presentation and in their geographic
      and cultural origin. The sessions focused on the role of these medications in
      selected resource poor settings in Africa and Asia now that access to anti
      retroviral therapy is increasing. The aims of the sessions were to (1) identify
      the actors involved in the diffusion of these alternative medicines for HIV/AIDS,
      (2) explore uses and forms, and the way these medicines are given legitimacy, (3)
      reflect on underlying processes of globalisation and cultural differentiation,
      and (4) define priority questions for future research in this area. This article
      presents the insights generated at the meeting, illustrated with some findings
      from the case studies (Uganda, Senegal, Benin, Burkina Faso, China and Indonesia)
      that were presented. These case studies reveal the wide range of actors who are
      involved in the marketing and supply of alternative medicines. Regulatory
      mechanisms are weak. The efficacy claims of alternative medicines often reinforce
      a biomedical paradigm for HIV/AIDS, and fit with a healthy living ideology
      promoted by AIDS care programs and support groups. The AIDSImpact session
      concluded that more interdisciplinary research is needed on the experience of
      people living with HIV/AIDS with these alternative medicines, and on the ways in
      which these products interact (or not) with anti-retroviral therapy at
      pharmacological as well as psychosocial levels.

PMID- 18616795
TI  - Adult nutrition and butterfly fitness: effects of diet quality on reproductive
      output, egg composition, and egg hatching success.
AB  - BACKGROUND: In the Lepidoptera it was historically believed that adult
      butterflies rely primarily on larval-derived nutrients for reproduction and
      somatic maintenance. However, recent studies highlight the complex interactions
      between storage reserves and adult income, and that the latter may contribute
      significantly to reproduction. Effects of adult diet were commonly assessed by
      determining the number and/or size of the eggs produced, whilst its consequences
      for egg composition and offspring viability were largely neglected (as is
      generally true for insects). We here specifically focus on these latter issues by
      using the fruit-feeding tropical butterfly Bicyclus anynana, which is highly
      dependent on adult-derived carbohydrates for reproduction. RESULTS: Adult diet of
      female B. anynana had pronounced effects on fecundity, egg composition and egg
      hatching success, with butterflies feeding on the complex nutrition of banana
      fruit performing best. Adding vitamins and minerals to a sucrose-based diet
      increased fecundity, but not offspring viability. All other groups (plain sucrose
      solution, sucrose solution enriched with lipids or yeast) had a substantially
      lower fecundity and egg hatching success compared to the banana group.
      Differences were particularly pronounced later in life, presumably indicating the
      depletion of essential nutrients in sucrose-fed females. Effects of adult diet on
      egg composition were not straightforward, indicating complex interactions among
      specific compounds. There was some evidence that total egg energy and water
      content were related to hatching success, while egg protein, lipid, glycogen and
      free carbohydrate content did not seem to limit successful development.
      CONCLUSION: The patterns shown here exemplify the complexity of reproductive
      resource allocation in B. anynana, and the need to consider egg composition and
      offspring viability when trying to estimate the effects of adult nutrition on
      fitness in this butterfly and other insects.

PMID- 18616796
TI  - Medication persistence rates and factors associated with persistence in patients
      following stroke: a cohort study.
AB  - BACKGROUND: Medication nonadherence can be as high as 50% and results in
      suboptimal patient outcomes. Stroke patients in particular can benefit from
      pharmacotherapy for thrombosis, hypertension, and dyslipidemia but are at high
      risk for medication nonpersistence. METHODS: Patients who were admitted to the
      Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, with stroke
      between January 1, 2001 and December 31, 2002 were analyzed. Data collected were
      pre-stroke function, stroke subtype, stroke severity, patient outcomes, and
      medication use at discharge, and six and 12 months post discharge. Medication
      persistence at six and 12 months and the factors associated with nonpersistence
      at six months were examined using multivariable stepwise logistic regression.
      RESULTS: At discharge, 420 patients (mean age 68.2 years, 55.7% male) were
      prescribed an average of 6.4 medications and mean prescription drug cost was $167
      monthly. Antihypertensive (91%) and antithrombotic (96%) drug use at discharge
      were frequent, antilipidemic (73%) and antihyperglycemic (25%) drug use were less
      common. Self-reported persistence at six and 12 months after stroke was high (>
      90%) for all categories. In the multivariable model of medication nonpersistence
      at six months, people aged 65 to 79 years were less likely to be nonpersistent
      with antihypertensive medications than people aged 80 years or more (Odds ratio
      (OR) 0.11, 95% Confidence Interval (CI) 0.03-0.39). Monthly drug costs of < $90
      or $90-199.99 were associated with greater nonpersistence, compared to monthly
      drug costs > or =$200 (OR 6.74, 95% CI 1.32-34.46 for < $90; OR 5.25, 95% CI 1.14
      24.25 for $90-199.99). For the antithrombotic drug category, people aged 65 to 79
      years were less likely to be nonpersistent than people aged 80 years or more (OR
      0.23, 95% CI 0.06-0.81), and people who were disabled before admission were more
      likely to be nonpersistent than those not disabled (OR 7.01, 95% CI 1.66-29.58).
      CONCLUSION: Patients reported high medication persistence rates six and 12 months
      after stroke. Identification of factors associated with nonpersistence (such as
      older age and prior disability) will help predict which patients are at higher
      risk for discontinuing their medications.

PMID- 18616797
TI  - Participants' perspective on maintaining behaviour change: a qualitative study
      within the European Diabetes Prevention Study.
AB  - BACKGROUND: The European Diabetes Prevention Study (EDIPS) is an RCT of diet and
      exercise interventions in people with impaired glucose tolerance. We undertook a
      qualitative study, nested within the EDIPS in Newcastle-upon-Tyne, UK, aiming to
      understand the experience of participants who maintained behaviour change, in
      order to inform future interventions. METHODS: Participants were purposively
      sampled, according to success criteria for diet and physical activity change
      maintenance, and invited to attend individual semi-structured interviews. Fifteen
      participants completed an interview and reflected on their experience over three
      to five years. We used the Framework method to analyse the transcribed data.
      RESULTS: Main themes were identified as factors that help (props) and those that
      hinder (burdens) behaviour change maintenance at different organisational levels:
      individual (both physical and psychological), social and environmental. Pre
      existing physical conditions (such as arthritis) and social demands (such as
      caring for an ageing relative) hindered, whereas the benefits of becoming fitter
      and of having social and professional support helped, participants in maintaining
      behaviour change. Participants' long term experiences highlighted the salience of
      the continuous change in their physical, social and environmental conditions over
      time. CONCLUSION: The construct of props and burdens facilitates a holistic view
      of participants' behaviour. Efforts to encourage behaviour change maintenance
      should take account of context and the way this changes over time, and should
      include strategies to address these issues. The experience of participants who
      maintain behaviour change highlights the challenges for the wider implementation
      of diabetes prevention strategies. TRIAL REGISTRATION: (ISRCTN 15670600).

PMID- 18616798
TI  - Validity of two physical activity questionnaires (IPAQ and PAQA) for Vietnamese
      adolescents in rural and urban areas.
AB  - BACKGROUND: Although physical activity is recognised to be an important
      determinant of health and nutritional status, few instruments have been developed
      to assess physical activity in developing countries. The aim of this study was to
      compare the validity of the short form of the International Physical Activity
      Questionnaire (IPAQ) and a locally adapted version of the Physical Activity
      Questionnaire for Adolescents (PAQA) for use in school going adolescents in rural
      and urban areas in Vietnam. METHODS: Sixteen year old adolescents from rural
      areas (n = 137) and urban areas (n = 90) completed the questionnaires in 2006.
      Test-retest reliability was assessed by comparing registrations after 2 weeks.
      Criterion validity was assessed by comparison with 7 days continuous
      accelerometer logging. Validity of the two methods was assessed using Spearman
      correlation coefficient, intra class correlation coefficients (ICC) and Kappa
      statistics. RESULTS: Reliability of both questionnaires was poor for both the
      IPAQ (ICC = 0.37) and the PAQA (ICC = 0.40). Criterion validity of both
      questionnaires was acceptable and similar for the IPAQ (rho = 0.21) and the PAQA
      (rho = 0.27) but a significantly lower validity was observed in rural areas. Both
      forms poorly estimated time spent on light, moderate and vigorous physical
      activity. Agreement of both questionnaires to classify individuals was also low
      but the IPAQ performed better than the PAQA. CONCLUSION: Both questionnaires have
      a similar and overall poor validity to be used as a population instrument in
      Vietnam. Low reliability and classification properties in rural areas call for
      further research for specific use in such settings.

PMID- 18616800
TI  - Male silver eels mature by swimming.
AB  - BACKGROUND: If European silver eels are prevented from reproductive migration,
      they remain in a prepubertal stage by dopaminergic inhibition of pituitary
      activity. Because this inhibition is likely a requirement for an extended female
      growth stage, we tested if it is sex-specific by subjecting both sexes to
      stimulation by GnRHa (Gonadotropin-Releasing Hormone agonist) - injection or 3
      months swimming in seawater. RESULTS: In contrast to females, males showed a two-
      to three-fold higher LHbeta (luteinising hormone beta subunit) - expression, a
      three- to five-fold higher GSI (Gonadosomatic index) and induced spermatogenesis
      when compared with the untreated control group. CONCLUSION: Dopaminergic
      inhibition is thus not effective in males and swimming results in natural
      maturation, probably via GnRH-release.

PMID- 18616799
TI  - Identification of genes influencing dendrite morphogenesis in developing
      peripheral sensory and central motor neurons.
AB  - BACKGROUND: Developing neurons form dendritic trees with cell type-specific
      patterns of growth, branching and targeting. Dendrites of Drosophila peripheral
      sensory neurons have emerged as a premier genetic model, though the molecular
      mechanisms that underlie and regulate their morphogenesis remain incompletely
      understood. Still less is known about this process in central neurons and the
      extent to which central and peripheral dendrites share common organisational
      principles and molecular features. To address these issues, we have carried out
      two comparable gain-of-function screens for genes that influence dendrite
      morphologies in peripheral dendritic arborisation (da) neurons and central RP2
      motor neurons. RESULTS: We found 35 unique loci that influenced da neuron
      dendrites, including five previously shown as required for da dendrite
      patterning. Several phenotypes were class-specific and many resembled those of
      known mutants, suggesting that genes identified in this study may converge with
      and extend known molecular pathways for dendrite development in da neurons. The
      second screen used a novel technique for cell-autonomous gene misexpression in
      RP2 motor neurons. We found 51 unique loci affecting RP2 dendrite morphology, 84%
      expressed in the central nervous system. The phenotypic classes from both screens
      demonstrate that gene misexpression can affect specific aspects of dendritic
      development, such as growth, branching and targeting. We demonstrate that these
      processes are genetically separable. Targeting phenotypes were specific to the
      RP2 screen, and we propose that dendrites in the central nervous system are
      targeted to territories defined by Cartesian co-ordinates along the antero
      posterior and the medio-lateral axes of the central neuropile. Comparisons
      between the screens suggest that the dendrites of peripheral da and central RP2
      neurons are shaped by regulatory programs that only partially overlap. We focused
      on one common candidate pathway controlled by the ecdysone receptor, and found
      that it promotes branching and growth of developing da neuron dendrites, but a
      role in RP2 dendrite development during embryonic and early larval stages was not
      apparent. CONCLUSION: We identified commonalities (for example, growth and
      branching) and distinctions (for example, targeting and ecdysone response) in the
      molecular and organizational framework that underlies dendrite development of
      peripheral and central neurons.

PMID- 18616801
TI  - Investigating selection on viruses: a statistical alignment approach.
AB  - BACKGROUND: Two problems complicate the study of selection in viral genomes:
      Firstly, the presence of genes in overlapping reading frames implies that
      selection in one reading frame can bias our estimates of neutral mutation rates
      in another reading frame. Secondly, the high mutation rates we are likely to
      encounter complicate the inference of a reliable alignment of genomes. To address
      these issues, we develop a model that explicitly models selection in overlapping
      reading frames. We then integrate this model into a statistical alignment
      framework, enabling us to estimate selection while explicitly dealing with the
      uncertainty of individual alignments. We show that in this way we obtain un
      biased selection parameters for different genomic regions of interest, and can
      improve in accuracy compared to using a fixed alignment. RESULTS: We run a series
      of simulation studies to gauge how well we do in selection estimation, especially
      in comparison to the use of a fixed alignment. We show that the standard practice
      of using a ClustalW alignment can lead to considerable biases and that estimation
      accuracy increases substantially when explicitly integrating over the uncertainty
      in inferred alignments. We even manage to compete favourably for general
      evolutionary distances with an alignment produced by GenAl. We subsequently run
      our method on HIV2 and Hepatitis B sequences. CONCLUSION: We propose that
      marginalizing over all alignments, as opposed to using a fixed one, should be
      considered in any parametric inference from divergent sequence data for which the
      alignments are not known with certainty. Moreover, we discover in HIV2 that
      double coding regions appear to be under less stringent selection than single
      coding ones. Additionally, there appears to be evidence for differential
      selection, where one overlapping reading frame is under positive and the other
      under negative selection.

PMID- 18616802
TI  - Isolation of specific and biologically active peptides that bind cells from
      patients with acute myeloid leukemia (AML).
AB  - PURPOSE: In a departure from conventional strategies to improve treatment outcome
      for myeloid malignancies, we report the isolation of leukemia-specific peptides
      using a phage display library screened with freshly obtained human myeloid
      leukemia cells. RESULTS: A phage display library was screened by 5 rounds of
      biopanning with freshly isolated human AML cells. Individual colonies were
      randomly picked and after purification, biologic activity (growth and
      differentiation) on fresh AML cells was profiled. Ten peptides were synthesized
      for further biological studies. Multiple peptides were found to selectively bind
      to acute myeloid leukemia (AML) cells. The peptides bound to leukemia cells, were
      internalized and could induce proliferation and/or differentiation in the target
      patient cells. Two of the peptides, HP-A2 and HP-G7, appeared to have a novel
      mechanism of inducing differentiation since they did not cause G1 arrest in
      cycling cells even as the expression of the differentiation marker CD11b
      increased. CONCLUSION: Peptide induced differentiation of leukemia cells offers a
      novel treatment strategy for myeloid malignancies, whereas their ability to
      induce proliferation could be harnessed to make cells more sensitive to
      chemotherapy. Conceptually, these leukemia specific peptides can also be used to
      refine diagnosis, document minimal residual disease, and selectively deliver
      toxins to malignant cells.

PMID- 18616804
TI  - Tau exon 10 alternative splicing and tauopathies.
AB  - Abnormalities of microtubule-associated protein tau play a central role in
      neurofibrillary degeneration in several neurodegenerative disorders that
      collectively called tauopathies. Six isoforms of tau are expressed in adult human
      brain, which result from alternative splicing of pre-mRNA generated from a single
      tau gene. Alternative splicing of tau exon 10 results in tau isoforms containing
      either three or four microtubule-binding repeats (3R-tau and 4R-tau,
      respectively). Approximately equal levels of 3R-tau and 4R-tau are expressed in
      normal adult human brain, but the 3R-tau/4R-tau ratio is altered in the brains in
      several tauopathies. Discovery of silence mutations and intronic mutations of tau
      gene in some individuals with frontotemporal dementia with Parkinsonism linked to
      chromosome 17 (FTDP-17), which only disrupt tau exon 10 splicing but do not alter
      tau's primary sequence, demonstrates that dysregulation of tau exon 10
      alternative splicing and consequently of 3R-tau/4R-tau balance is sufficient to
      cause neurodegeneration and dementia. Here, we review the gene structure,
      transcripts and protein isoforms of tau, followed by the regulation of exon 10
      splicing that determines the expression of 3R-tau or 4R-tau. Finally,
      dysregulation of exon 10 splicing of tau in several tauopathies is discussed.
      Understanding the molecular mechanisms by which tau exon 10 splicing is regulated
      and how it is disrupted in tauopathies will provide new insight into the
      mechanisms of these tauopathies and help identify new therapeutic targets to
      treat these disorders.

PMID- 18616803
TI  - Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L,
      urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA
      and CA 19-9 in colorectal cancer.
AB  - BACKGROUND: Cathepsin B and L (CATB, CATL), urokinase-type plasminogen activator
      (uPA) and its inhibitor PAI-1 play an important role in colorectal cancer
      invasion. The tumor marker utility and prognostic relevance of these proteases
      have not been evaluated in the same experimental setting and compared with that
      of CEA and CA-19-9. METHODS: Protease, CEA and CA 19-9 serum or plasma levels
      were determined in 56 patients with colorectal cancer, 25 patients with
      ulcerative colitis, 26 patients with colorectal adenomas and 35 tumor-free
      control patients. Protease, CEA, CA 19-9 levels have been determined by ELISA and
      electrochemiluminescence immunoassay, respectively; their sensitivity,
      specificity, diagnostic accuracy have been calculated and correlated with
      clinicopathological staging. RESULTS: The protease antigen levels were
      significantly higher in colorectal cancer compared with other groups. Sensitivity
      of PAI-1 (94%), CATB (82%), uPA (69%), CATL (41%) were higher than those of CEA
      or CA 19-9 (30% and 18%, respectively). PAI-1, CATB and uPA demonstrated a better
      accuracy than CEA or CA 19-9. A combination of PAI-1 with CATB or uPA exhibited
      the highest sensitivity value (98%). High CATB, PAI-1, CEA and CA 19-9 levels
      correlated with advanced Dukes stages. CATB (P = 0.0004), CATL (P = 0.02), PAI-1
      (P = 0.01) and CA 19-9 (P = 0.004) had a significant prognostic impact. PAI-1 (P
      = 0.001), CATB (P = 0.04) and CA 19-9 (P = 0.02) proved as independent prognostic
      variables. CONCLUSION: At the time of clinical detection proteases are more
      sensitive indicators for colorectal cancer than the commonly used tumor markers.
      Determinations of CATB, CATL and PAI-1 have a major prognostic impact in patients
      with colorectal cancer.

PMID- 18616805
TI  - A monoclonal antibody marker for the exclusion-zone filaments of Trypanosoma
      brucei.
AB  - BACKGROUND: Trypanosoma brucei is a haemoflagellate pathogen of man, wild
      animals and domesticated livestock in central and southern Africa. In all life
      cycle stages this parasite has a single mitochondrion that contains a uniquely
      organised genome that is condensed into a flat disk-like structure called the
      kinetoplast. The kinetoplast is essential for insect form procyclic cells and
      therefore is a potential drug target. The kinetoplast is unique in nature because
      it consists of novel structural proteins and thousands of circular, interlocking,
      DNA molecules (kDNA). Secondly, kDNA replication is critically timed to coincide
      with nuclear S phase and new flagellum biogenesis. Thirdly, the kinetoplast is
      physically attached to the flagellum basal bodies via a structure called the
      tripartite attachment complex (TAC). The TAC consists of unilateral filaments
      (within the mitochondrion matrix), differentiated mitochondrial membranes and
      exclusion-zone filaments that extend from the distal end of the basal bodies. To
      date only one protein, p166, has been identified to be a component of the TAC.
      RESULTS: In the work presented here we provide data based on a novel EM technique
      developed to label and characterise cytoskeleton structures in permeabilised
      cells without extraction of mitochondrion membranes. We use this protocol to
      provide data on a new monoclonal antibody reagent (Mab 22) and illustrate the
      precise localisation of basal body-mitochondrial linker proteins. Mab 22 binds to
      these linker proteins (exclusion-zone filaments) and provides a new tool for the
      characterisation of cytoskeleton mediated kinetoplast segregation. CONCLUSION:
      The antigen(s) recognised by Mab 22 are cytoskeletal, insensitive to extraction
      by high concentrations of non-ionic detergent, extend from the proximal region of
      basal bodies and bind to the outer mitochondrial membrane. This protein(s) is the
      first component of the TAC exclusion-zone fibres to be identified. Mab 22 will
      therefore be important in characterising TAC biogenesis.

PMID- 18616806
TI  - Comparative analysis reveals signatures of differentiation amid genomic
      polymorphism in Lake Malawi cichlids.
AB  - BACKGROUND: Cichlid fish from East Africa are remarkable for phenotypic and
      behavioral diversity on a backdrop of genomic similarity. In 2006, the Joint
      Genome Institute completed low coverage survey sequencing of the genomes of five
      phenotypically and ecologically diverse Lake Malawi species. We report a
      computational and comparative analysis of these data that provides insight into
      the mechanisms that make closely related species different from one another.
      RESULTS: We produced assemblies for the five species ranging in aggregate length
      from 68 to 79 megabase pairs, identified putative orthologs for more than 12,000
      human genes, and predicted more than 32,000 cross-species single nucleotide
      polymorphisms (SNPs). Nucleotide diversity was lower than that found among
      laboratory strains of the zebrafish. We collected around 36,000 genotypes to
      validate a subset of SNPs within and among populations and across multiple
      individuals of about 75 Lake Malawi species. Notably, there were no fixed
      differences observed between focal species nor between major lineages. Roughly 3%
      to 5% of loci surveyed are statistical outliers for genetic differentiation (FST)
      within species, between species, and between major lineages. Outliers for FST are
      candidate genes that may have experienced a history of natural selection in the
      Malawi lineage. CONCLUSION: We present a novel genome sequencing strategy, which
      is useful when evolutionary diversity is the question of interest. Lake Malawi
      cichlids are phenotypically and behaviorally diverse, but they appear genetically
      like a subdivided population. The unique structure of Lake Malawl cichlid genomes
      should facilitate conceptually new experiments, employing SNPs to identity
      genotype-phenotype association, using the entire species flock as a mapping
      panel.

PMID- 18616807
TI  - The origin and evolution of plant cystatins and their target cysteine proteinases
      indicate a complex functional relationship.
AB  - BACKGROUND: Cystatins and their putative targets, the families of cysteine
      proteinases C1A and C13 play key roles in plants. Comparative genomic analyses
      are powerful tools to obtain valuable insights into the conservation and
      evolution of the proteinases and their proteinaceous inhibitors, and could aid to
      elucidate issues concerning the function of these proteins. RESULTS: We have
      performed an evolutionary comparative analysis of cysteine proteinases C1A and
      C13 and their putative inhibitors in representative species of different
      taxonomic groups that appeared during the evolution of the Viridiplantae. The
      results indicate that whereas C1A cysteine proteinases are present in all
      taxonomic groups, cystatins and C13 cysteine proteinases are absent in some basal
      groups. Moreover, gene duplication events have been associated to the increasing
      structural and functional complexities acquired in land plants. CONCLUSION:
      Comparative genomic analyses have provided us valuable insights into the
      conservation and evolution of the cystatin inhibitory family and their putative
      targets, the cysteine proteinases from families C1A and C13. Functionality of
      both families of proteins in plants must be the result of a coevolutionary
      process that might have occurred during the evolution of basal and land plants
      leading to a complex functional relationship among them.

PMID- 18616808
TI  - Phylogeny and biogeography of African Murinae based on mitochondrial and nuclear
      gene sequences, with a new tribal classification of the subfamily.
AB  - BACKGROUND: Within the subfamily Murinae, African murines represent 25% of
      species biodiversity, making this group ideal for detailed studies of the
      patterns and timing of diversification of the African endemic fauna and its
      relationships with Asia. Here we report the results of phylogenetic analyses of
      the endemic African murines through a broad sampling of murine diversity from all
      their distribution area, based on the mitochondrial cytochrome b gene and the two
      nuclear gene fragments (IRBP exon 1 and GHR). RESULTS: A combined analysis of one
      mitochondrial and two nuclear gene sequences consistently identified and robustly
      supported ten primary lineages within Murinae. We propose to formalize a new
      tribal arrangement within the Murinae that reflects this phylogeny. The diverse
      African murine assemblage includes members of five of the ten tribes and clearly
      derives from multiple faunal exchanges between Africa and Eurasia. Molecular
      dating analyses using a relaxed Bayesian molecular clock put the first
      colonization of Africa around 11 Mya, which is consistent with the fossil record.
      The main period of African murine diversification occurred later following
      disruption of the migration route between Africa and Asia about 7-9 Mya. A second
      period of interchange, dating to around 5-6.5 Mya, saw the arrival in Africa of
      Mus (leading to the speciose endemic Nannomys), and explains the appearance of
      several distinctive African lineages in the late Miocene and Pliocene fossil
      record of Eurasia. CONCLUSION: Our molecular survey of Murinae, which includes
      the most complete sampling so far of African taxa, indicates that there were at
      least four separate radiations within the African region, as well as several
      phases of dispersal between Asia and Africa during the last 12 My. We also
      reconstruct the phylogenetic structure of the Murinae, and propose a new
      classification at tribal level for this traditionally problematic group.

PMID- 18616809
TI  - Systematic genetic array analysis links the Saccharomyces cerevisiae SAGA/SLIK
      and NuA4 component Tra1 to multiple cellular processes.
AB  - BACKGROUND: Tra1 is an essential 437-kDa component of the Saccharomyces
      cerevisiae SAGA/SLIK and NuA4 histone acetyltransferase complexes. It is a member
      of a group of key signaling molecules that share a carboxyl-terminal domain
      related to phosphatidylinositol-3-kinase but unlike many family members, it lacks
      kinase activity. To identify genetic interactions for TRA1 and provide insight
      into its function we have performed a systematic genetic array analysis (SGA) on
      tra1SRR3413, an allele that is defective in transcriptional regulation. RESULTS:
      The SGA analysis revealed 114 synthetic slow growth/lethal (SSL) interactions for
      tra1SRR3413. The interacting genes are involved in a range of cellular processes
      including gene expression, mitochondrial function, and membrane sorting/protein
      trafficking. In addition many of the genes have roles in the cellular response to
      stress. A hierarchal cluster analysis revealed that the pattern of SSL
      interactions for tra1SRR3413 most closely resembles deletions of a group of
      regulatory GTPases required for membrane sorting/protein trafficking. Consistent
      with a role for Tra1 in cellular stress, the tra1SRR3413 strain was sensitive to
      rapamycin. In addition, calcofluor white sensitivity of the strain was enhanced
      by the protein kinase inhibitor staurosporine, a phenotype shared with the Ada
      components of the SAGA/SLIK complex. Through analysis of a GFP-Tra1 fusion we
      show that Tra1 is principally localized to the nucleus. CONCLUSION: We have
      demonstrated a genetic association of Tra1 with nuclear, mitochondrial and
      membrane processes. The identity of the SSL genes also connects Tra1 with
      cellular stress, a result confirmed by the sensitivity of the tra1SRR3413 strain
      to a variety of stress conditions. Based upon the nuclear localization of GFP
      Tra1 and the finding that deletion of the Ada components of the SAGA complex
      result in similar phenotypes as tra1SRR3413, we suggest that the effects of
      tra1SRR3413 are mediated, at least in part, through its role in the SAGA complex.

PMID- 18616810
TI  - The influence of body composition on therapeutic hypothermia: a prospective
      observational study of patients after cardiac arrest.
AB  - INTRODUCTION: Patients after out-of-hospital cardiac arrest (OHCA) benefit from
      therapeutic hypothermia for 24 hours. The time needed to reach hypothermia
      (target temperature of 32 degrees C to 34 degrees C) varies widely. In this
      study, we explore the relation between measures of body composition and the time
      needed to reach target temperature with hypothermia. METHOD: We conducted a
      prospective observational study in patients treated with hypothermia after OHCA.
      Data collected included weight and height, body composition by anthropometric
      measures and by single-frequency body impedance, and waist-to-hip ratio. Analysis
      of concordance between impedance and anthropometric measures and hazard ratios of
      achieving target temperature (event) corrected for different body composition
      measures. RESULTS: Twenty-seven patients were included. The median (interquartile
      range) time to reach target temperature after admission to the intensive care
      unit was 191 (105 to 382) minutes. Intraclass correlation for total body fat
      (TBF) measures was 0.94 (95% confidence interval [CI] 0.89 to 0.97). Only TBF
      percentage (anthropometrics by the Durnin's table) appeared to be associated with
      time to reach target temperature: 0.93 (95% CI 0.87 to 0.99; P = 0.03).
      CONCLUSION: The body composition measures from single-frequency impedance and
      anthropometrics appear to be very concordant. Only TBF percentage
      (anthropometrics) showed a significant but clinically irrelevant influence on
      time needed to achieve target temperature with hypothermia. We conclude that
      there are no indications to adjust current cooling practice toward the body
      composition of patients.

PMID- 18616811
TI  - A single dose of pegfilgrastim compared with daily filgrastim for supporting
      neutrophil recovery in patients treated for low-to-intermediate risk acute
      myeloid leukemia: results from a randomized, double-blind, phase 2 trial.
AB  - BACKGROUND: Patients with acute myeloid leukemia (AML) are often neutropenic as a
      result of their disease. Furthermore, these patients typically experience
      profound neutropenia following induction and/or consolidation chemotherapy and
      this may result in serious, potentially life-threatening, infection. This
      randomized, double-blind, phase 2 clinical trial compared the efficacy and
      tolerability of pegfilgrastim with filgrastim for assisting neutrophil recovery
      following induction and consolidation chemotherapy for de novo AML in patients
      with low-to-intermediate risk cytogenetics. METHODS: Patients (n = 84) received
      one or two courses of standard induction chemotherapy (idarubicin + cytarabine),
      followed by one course of consolidation therapy (high-dose cytarabine) if
      complete remission was achieved. They were randomized to receive either single
      dose pegfilgrastim 6 mg or daily filgrastim 5 mug/kg, beginning 24 hours after
      induction and consolidation chemotherapy. RESULTS: The median time to recovery
      from severe neutropenia was 22.0 days for both pegfilgrastim (n = 42) and
      filgrastim (n = 41) groups during Induction 1 (difference 0.0 days; 95% CI: -1.9
      to 1.9). During Consolidation, recovery occurred after a median of 17.0 days for
      pegfilgrastim versus 16.5 days for filgrastim (difference 0.5 days; 95% CI: -1.1
      to 2.1). Therapeutic pegfilgrastim serum concentrations were maintained
      throughout neutropenia. Pegfilgrastim was well tolerated, with an adverse event
      profile similar to that of filgrastim. CONCLUSION: These data suggest no
      clinically meaningful difference between a single dose of pegfilgrastim and
      multiple daily doses of filgrastim for shortening the duration of severe
      neutropenia following chemotherapy in de novo AML patients with low-to
      intermediate risk cytogenetics. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00114764.

PMID- 18616812
TI  - Language and rigour in qualitative research: problems and principles in analyzing
      data collected in Mandarin.
AB  - In collaborative qualitative research in Asia, data are usually collected in the
      national language, and this poses challenges for analysis. Translation of
      transcripts to a language common to the whole research team is time consuming and
      expensive; meaning can easily be lost in translation; and validity of the data
      may be compromised in this process. We draw on several published examples from
      public health research conducted in mainland China, to highlight how language can
      influence rigour in the qualitative research process; for each problem we suggest
      potential solutions based on the methods used in one of our research projects in
      China. Problems we have encountered include obtaining sufficient depth and detail
      in qualitative data; deciding on language for data collection; managing data
      collected in Mandarin; and the influence of language on interpreting meaning. We
      have suggested methods for overcoming problems associated with collecting,
      analysing, and interpreting qualitative data in a local language, that we think
      help maintain analytical openness in collaborative qualitative research. We
      developed these methods specifically in research conducted in Mandarin in
      mainland China; but they need further testing in other countries with data
      collected in other languages. Examples from other researchers are needed.

PMID- 18616813
TI  - Effect of hydrocephalus on rat brain extracellular compartment.
AB  - BACKGROUND: The cerebral cortex may be compressed in hydrocephalus and some
      experiments suggest that movement of extracellular substances through the cortex
      is impaired. We hypothesized that the extracellular compartment is reduced in
      size and that the composition of the extracellular compartment changes in rat
      brains with kaolin-induced hydrocephalus. METHODS: We studied neonatal (newborn)
      onset hydrocephalus for 1 or 3 weeks, juvenile (3 weeks) onset hydrocephalus for
      3-4 weeks or 9 months, and young adult (10 weeks) onset hydrocephalus for 2
      weeks, after kaolin injection. Freeze substitution electron microscopy was used
      to measure the size of the extracellular compartment. Western blotting and
      immunohistochemistry with quantitative image densitometry was used to study the
      extracellular matrix constituents, phosphacan, neurocan, NG2, decorin, biglycan,
      and laminin. RESULTS: The extracellular space in cortical layer 1 was reduced
      significantly from 16.5 to 9.6% in adult rats with 2 weeks duration
      hydrocephalus. Western blot and immunohistochemistry showed that neurocan
      increased only in the periventricular white matter following neonatal induction
      and 3 weeks duration hydrocephalus. The same rats showed mild decorin increases
      in white matter and around cortical neurons. Juvenile and adult onset
      hydrocephalus was associated with no significant changes. CONCLUSION: We conclude
      that compositional changes in the extracellular compartment are negligible in
      cerebral cortex of hydrocephalic rats at various ages. Therefore, the functional
      change related to extracellular fluid flow should be reversible.

PMID- 18616814
TI  - Spinal cord compression by a solitary metastasis from a low grade leydig cell
      tumour: a case report and review of the literature.
AB  - BACKGROUND: Leydig tumour is rare and there are only three cases with metastatic
      disease reported. CASE PRESENTATION: A 52 year-old Caucasian male was admitted,
      on emergency basis to the Orthopaedic Department with six weeks history of
      increasing midthoracic back pain, change in gait, poor balance, subjective
      weakness and numbness of the lower trunk and legs. MRI scan showed change in the
      signal intensity of T4 and T5 vertebral body but their height were maintained.
      Urgent T4 and T5 corpectomies, decompression of the spinal cord and
      reconstruction of the vertebral bodies were performed followed by radiotherapy.
      Neurological status significantly improved with a mild residual numbness over the
      dorsum of the right foot. The histology of the excised tumour was identical to
      the primary. At 2 years follow-up visit the patient is neurologically stable and
      disease free without other organs metastases. CONCLUSION: This is the first case
      in English literature, which shows that spinal metastases could occur even in the
      early stage of Leydig cell tumour, without other organs involvement. Aggressive
      surgical management of spinal metastases combined with post operative
      radiotherapy can give a better chance for long survivorship.

PMID- 18616815
TI  - Complex myograph allows the examination of complex muscle contractions for the
      assessment of muscle force, shortening, velocity, and work in vivo.
AB  - BACKGROUND: The devices used for in vivo examination of muscle contractions
      assess only pure force contractions and the so-called isokinetic contractions. In
      isokinetic experiments, the extremity and its muscle are artificially moved with
      constant velocity by the measuring device, while a tetanic contraction is induced
      in the muscle, either by electrical stimulation or by maximal voluntary
      activation. With these systems, experiments cannot be performed at pre-defined,
      constant muscle length, single contractions cannot be evaluated individually and
      the separate examination of the isometric and the isotonic components of single
      contractions is not possible. METHODS: The myograph presented in our study has
      two newly developed technical units, i.e. a). a counterforce unit which can load
      the muscle with an adjustable, but constant force and b). a length-adjusting unit
      which allows for both the stretching and the contraction length to be infinitely
      adjustable independently of one another. The two units support the examination of
      complex types of contraction and store the counterforce and length-adjusting
      settings, so that these conditions may be accurately reapplied in later sessions.
      RESULTS: The measurement examples presented show that the muscle can be brought
      to every possible pre-stretching length and that single isotonic or complex
      isometric-isotonic contractions may be performed at every length. The applied
      forces act during different phases of contraction, resulting into different pre-
      and after-loads that can be kept constant - uninfluenced by the contraction.
      Maximal values for force, shortening, velocity and work may be obtained for
      individual muscles. This offers the possibility to obtain information on the
      muscle status and to monitor its changes under non-invasive measurement
      conditions. CONCLUSION: With the Complex Myograph, the whole spectrum of a
      muscle's mechanical characteristics may be assessed.

PMID- 18616816
TI  - Soluble histone H2AX is induced by DNA replication stress and sensitizes cells to
      undergo apoptosis.
AB  - BACKGROUND: Chromatin-associated histone H2AX is a key regulator of the cellular
      responses to DNA damage. However, non-nucleosomal functions of histone H2AX are
      poorly characterized. We have recently shown that soluble H2AX can trigger
      apoptosis but the mechanisms leading to non-chromatin-associated H2AX are
      unclear. Here, we tested whether stalling of DNA replication, a common event in
      cancer cells and the underlying mechanism of various chemotherapeutic agents, can
      trigger increased soluble H2AX. RESULTS: Transient overexpression of H2AX was
      found to lead to a detectable fraction of soluble H2AX and was associated with
      increased apoptosis. This effect was enhanced by the induction of DNA replication
      stress using the DNA polymerase alpha inhibitor aphidicolin. Cells manipulated to
      stably express H2AX did not contain soluble H2AX, however, short-term treatment
      with aphidicolin (1 h) resulted in detectable amounts of H2AX in the soluble
      nuclear fraction and enhanced apoptosis. Similarly, soluble endogenous H2AX was
      detected under these conditions. We found that excessive soluble H2AX causes
      chromatin aggregation and inhibition of ongoing gene transcription as evidenced
      by the redistribution and/or loss of active RNA polymerase II as well as the
      transcriptional co-activators CBP and p300. CONCLUSION: Taken together, these
      results show that DNA replication stress rapidly leads to increased soluble H2AX
      and that non-chromatin-associated H2AX can sensitize cells to undergo apoptosis.
      Our findings encourage further studies to explore H2AX and the cellular pathways
      that control its expression as anti-cancer drug targets.

PMID- 18616817
TI  - Altered behavior and digestive outcomes in adult male rats primed with minimal
      colon pain as neonates.
AB  - BACKGROUND: Neonatal colon irritation (CI; pain or inflammation) given for 2
      weeks prior to postnatal day 22 (PND22), causes long-lasting functional disorders
      in rats that can be seen 6 months after the initial insult. This study looked at
      the effect of varying the frequency and duration of neonatal CI on the rate of
      growth, digestive outcomes, exploratory activity, and colon and skin sensitivity
      in adult rats. METHODS: Male Sprague-Dawley rats were given CI using repeated
      colorectal distension (CRD) at different time intervals and for varying durations
      starting at PND 8, 10 or 14. Control rats were handled by the investigator
      without any intracolonic insertion. Further experiments were done on adult rats.
      Digestive outcomes (food and water consumption, fecal and urinary outputs) were
      measured using metabolic cages. Exploratory behavior was measured using digital
      video tracking in an open field. Cutaneous sensitivity was assessed by measuring
      the responses to mechanical and heat stimuli applied to the shaved abdomen or
      hind paws. Visceral sensitivity was measured by recording electromyographic
      responses, under light isoflurane anesthesia, from the external oblique muscles
      in response to CRD. RESULTS: No significant weight differences were observed
      between CI and control rats. Exploratory behavior was reduced in rats with
      neonatal CI compared to control. Digestive outputs and somatic and visceral
      sensitivity changed between different treatment groups with earlier and more
      frequent insults yielding a higher deviation from normal. CONCLUSION: The
      diversity of behavioral and digestive symptoms in these rats parallels the
      diversity of symptoms in patients with functional gastrointestinal disorders and
      is consistent with global plastic changes affecting more than one system in the
      organism.

PMID- 18616818
TI  - Methods for the thematic synthesis of qualitative research in systematic reviews.
AB  - BACKGROUND: There is a growing recognition of the value of synthesising
      qualitative research in the evidence base in order to facilitate effective and
      appropriate health care. In response to this, methods for undertaking these
      syntheses are currently being developed. Thematic analysis is a method that is
      often used to analyse data in primary qualitative research. This paper reports on
      the use of this type of analysis in systematic reviews to bring together and
      integrate the findings of multiple qualitative studies. METHODS: We describe
      thematic synthesis, outline several steps for its conduct and illustrate the
      process and outcome of this approach using a completed review of health promotion
      research. Thematic synthesis has three stages: the coding of text 'line-by-line';
      the development of 'descriptive themes'; and the generation of 'analytical
      themes'. While the development of descriptive themes remains 'close' to the
      primary studies, the analytical themes represent a stage of interpretation
      whereby the reviewers 'go beyond' the primary studies and generate new
      interpretive constructs, explanations or hypotheses. The use of computer software
      can facilitate this method of synthesis; detailed guidance is given on how this
      can be achieved. RESULTS: We used thematic synthesis to combine the studies of
      children's views and identified key themes to explore in the intervention
      studies. Most interventions were based in school and often combined learning
      about health benefits with 'hands-on' experience. The studies of children's views
      suggested that fruit and vegetables should be treated in different ways, and that
      messages should not focus on health warnings. Interventions that were in line
      with these suggestions tended to be more effective. Thematic synthesis enabled us
      to stay 'close' to the results of the primary studies, synthesising them in a
      transparent way, and facilitating the explicit production of new concepts and
      hypotheses. CONCLUSION: We compare thematic synthesis to other methods for the
      synthesis of qualitative research, discussing issues of context and rigour.
      Thematic synthesis is presented as a tried and tested method that preserves an
      explicit and transparent link between conclusions and the text of primary
      studies; as such it preserves principles that have traditionally been important
      to systematic reviewing.

PMID- 18616819
TI  - Pericardial cyst: an unusual cause of pneumonia.
AB  - INTRODUCTION: Pericardial cysts occur rarely with an incidence rate of 1 per
      100,000. They are usually detected by chance and are clinically silent in most
      cases. CASE PRESENTATION: We report the case of a 66 year old Irish male, with
      signs and symptoms of pneumonia. A chest X-Ray confirmed left lower lobe
      consolidation. Further imaging including a CT thorax identified a large
      pericardial cyst as the cause of the symptoms. CONCLUSION: Although pericardial
      cysts are usually asymptomatic, they can present with chest pain and symptoms of
      respiratory tract infection.

PMID- 18616820
TI  - Development of the knee quality of life (KQoL-26) 26-item questionnaire: data
      quality, reliability, validity and responsiveness.
AB  - BACKGROUND: This article describes the development and validation of a self
      reported questionnaire, the KQoL-26, that is based on the views of patients with
      a suspected ligamentous or meniscal injury of the knee that assesses the impact
      of their knee problem on the quality of their lives. METHODS: Patient interviews
      and focus groups were used to derive questionnaire content. The instrument was
      assessed for data quality, reliability, validity, and responsiveness using data
      from a randomised trial and patient survey about general practitioners' use of
      Magnetic Resonance Imaging for patients with a suspected ligamentous or meniscal
      injury. RESULTS: Interview and focus group data produced a 40-item questionnaire
      designed for self-completion. 559 trial patients and 323 survey patients
      responded to the questionnaire. Following principal components analysis and Rasch
      analysis, 26 items were found to contribute to three scales of knee-related
      quality of life: physical functioning, activity limitations, and emotional
      functioning. Item-total correlations ranged from 0.60-0.82. Cronbach's alpha and
      test retest reliability estimates were 0.91-0.94 and 0.80-0.93 respectively.
      Hypothesised correlations with the Lysholm Knee Scale, EQ-5D, SF-36 and knee
      symptom questions were evidence for construct validity. The instrument produced
      highly significant change scores for 65 trial patients indicating that their knee
      was a little or somewhat better at six months. The new instrument had higher
      effect sizes (range 0.86-1.13) and responsiveness statistics (range 1.50-2.13)
      than the EQ-5D and SF-36. CONCLUSION: The KQoL-26 has good evidence for internal
      reliability, test-retest reliability, validity and responsiveness, and is
      recommended for use in randomised trials and other evaluative studies of patients
      with a suspected ligamentous or meniscal injury.

PMID- 18616821
TI  - Identification of a panel of sensitive and specific DNA methylation markers for
      squamous cell lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death in men and women in
      the United States and Western Europe. Over 160,000 Americans die of this disease
      every year. The five-year survival rate is 15% - significantly lower than that of
      other major cancers. Early detection is a key factor in increasing lung cancer
      patient survival. DNA hypermethylation is recognized as an important mechanism
      for tumor suppressor gene inactivation in cancer and could yield powerful
      biomarkers for early detection of lung cancer. Here we focused on developing DNA
      methylation markers for squamous cell carcinoma of the lung. Using the sensitive,
      high-throughput DNA methylation analysis technique MethyLight, we examined the
      methylation profile of 42 loci in a collection of 45 squamous cell lung cancer
      samples and adjacent non-tumor lung tissues from the same patients. RESULTS: We
      identified 22 loci showing significantly higher DNA methylation levels in tumor
      tissue than adjacent non-tumor lung. Of these, eight showed highly significant
      hypermethylation in tumor tissue (p < 0.0001): GDNF, MTHFR, OPCML, TNFRSF25,
      TCF21, PAX8, PTPRN2 and PITX2. Used in combination on our specimen collection,
      this eight-locus panel showed 95.6% sensitivity and specificity. CONCLUSION: We
      have identified 22 DNA methylation markers for squamous cell lung cancer, several
      of which have not previously been reported to be methylated in any type of human
      cancer. The top eight markers show great promise as a sensitive and specific DNA
      methylation marker panel for squamous cell lung cancer.

PMID- 18616822
TI  - Design considerations in a sib-pair study of linkage for susceptibility loci in
      cancer.
AB  - BACKGROUND: Modern approaches to identifying new genes associated with disease
      allow very fine analysis of association and can be performed in population based
      case-control studies. However, the sibpair design is still valuable because it
      requires few assumptions other than acceptably high penetrance to identify
      genetic loci. METHODS: We conducted simulation studies to assess the impact of
      design factors on relative efficiency for a linkage study of colorectal cancer.
      We considered two test statistics, one comparing the mean IBD probability in
      affected pairs to its null value of 0.5, and one comparing the mean IBD
      probabilities between affected and discordant pairs. We varied numbers of parents
      available, numbers of affected and unaffected siblings, reconstructing the
      genotype of an unavailable affected sibling by a spouse and offspring, and
      elimination of sibships where the proband carries a mutation at another locus.
      RESULTS: Power and efficiency were most affected by the number of affected sibs,
      the number of sib pairs genotyped, and the risk attributable to linked and
      unlinked loci. Genotyping unaffected siblings added little power for low
      penetrance models, but improved validity of tests when there was genetic
      heterogeneity and for multipoint testing. The efficiency of the concordant-only
      test was nearly always better than the concordant-discordant test. Replacement of
      an unavailable affected sibling by a spouse and offspring recovered some linkage
      information, particularly if several offspring were available. In multipoint
      analysis, the concordant-only test was showed a small anticonservative bias at 5
      cM, while the multipoint concordant-discordant test was generally the most
      powerful test, and was not biased away from the null at 5 cM. CONCLUSION:
      Genotyping parents and unaffected siblings is useful for detecting genotyping
      errors and if allele frequencies are uncertain. If adequate allele frequency data
      are available, we suggest a single-point affecteds-only analysis for an initial
      scan, followed by a multipoint analysis of affected and unaffected members of all
      available sibships with additional markers around initial hits.

PMID- 18616824
TI  - Comparison of angiogenesis-related factor expression in primary tumor cultures
      under normal and hypoxic growth conditions.
AB  - BACKGROUND: A localized hypoxic environment occurs during tumor growth
      necessitating an angiogenic response or tumor necrosis results. Novel cancer
      treatment strategies take advantage of tumor-induced vascularisation by combining
      standard chemotherapeutic agents with angiogenesis-inhibiting agents. This has
      extended the progression-free interval and prolonged survival in patients with
      various types of cancer. We postulated that the expression levels of angiogenesis
      related proteins from various primary tumor cultures would be greater under
      hypoxic conditions than under normoxia. METHODS: Fifty cell sources, including
      both immortalized cell lines and primary carcinoma cells, were incubated under
      normoxic conditions for 48 hours. Then, cells were either transferred to a
      hypoxic environment (1% O2) or maintained at normoxic conditions for an
      additional 48 hours. Cell culture media from both conditions was collected and
      analyzed via an ELISA-based assay to determine expression levels of 11
      angiogenesis-related factors: VEGF, PDGF-AA, PDGF-AA/BB, IL-8, bFGF/FGF-2, EGF,
      IP-10/CXCL10, Flt-3 ligand, TGF-beta1, TGF-beta2, and TGF-beta3. RESULTS: A
      linear correlation between normoxic and hypoxic growth conditions exists for
      expression levels of eight of eleven angiogenesis-related proteins tested
      including: VEGF, IL-8, PDGF-AA, PDGF-AA/BB, TGF-beta1, TGF-beta2, EGF, and IP-10.
      For VEGF, the target of current therapies, this correlation between hypoxia and
      higher cytokine levels was greater in primary breast and lung carcinoma cells
      than in ovarian carcinoma cells or tumor cell lines. Of interest, patient cell
      isolates differed in the precise pattern of elevated cytokines. CONCLUSION: As
      linear correlations exist between expression levels of angiogenic factors under
      normoxic and hypoxic conditions in vitro, we propose that explanted primary cells
      may be used to probe the in vivo hypoxic environment. Furthermore, differential
      expression levels for each sample across all proteins examined suggests it may be
      possible to build a predictor for angiogenesis-related anticancer agents, as each
      sample has a unique expression profile. Further studies should be performed to
      correlate in vitro protein expression levels of angiogenesis-related factors with
      in vivo patient response.

PMID- 18616823
TI  - Select cognitive deficits in vasoactive intestinal peptide deficient mice.
AB  - BACKGROUND: The neuropeptide vasoactive intestinal peptide (VIP) is widely
      distributed in the adult central nervous system where this peptide functions to
      regulate synaptic transmission and neural excitability. The expression of VIP and
      its receptors in brain regions implicated in learning and memory functions,
      including the hippocampus, cortex, and amygdala, raise the possibility that this
      peptide may function to modulate learned behaviors. Among other actions, the loss
      of VIP has a profound effect on circadian timing and may specifically influence
      the temporal regulation of learning and memory functions. RESULTS: In the present
      study, we utilized transgenic VIP-deficient mice and the contextual fear
      conditioning paradigm to explore the impact of the loss of this peptide on a
      learned behavior. We found that VIP-deficient mice exhibited normal shock-evoked
      freezing behavior and increases in corticosterone. Similarly, these mutant mice
      exhibited no deficits in the acquisition or recall of the fear-conditioned
      behavior when tested 24-hours after training. The VIP-deficient mice exhibited a
      significant reduction in recall when tested 48-hours or longer after training.
      Surprisingly, we found that the VIP-deficient mice continued to express circadian
      rhythms in the recall of the training even in those individual mice whose wheel
      running wheel activity was arrhythmic. One mechanistic explanation is suggested
      by the finding that daily rhythms in the expression of the clock gene Period2
      continue in the hippocampus of VIP-deficient mice. CONCLUSION: Together these
      data suggest that the neuropeptide VIP regulates the recall of at least one
      learned behavior but does not impact the circadian regulation of this behavior.

PMID- 18616825
TI  - Logical Analysis of Data (LAD) model for the early diagnosis of acute ischemic
      stroke.
AB  - BACKGROUND: Strokes are a leading cause of morbidity and the first cause of adult
      disability in the United States. Currently, no biomarkers are being used
      clinically to diagnose acute ischemic stroke. A diagnostic test using a blood
      sample from a patient would potentially be beneficial in treating the disease.
      RESULTS: A classification approach is described for differentiating between
      proteomic samples of stroke patients and controls, and a second novel predictive
      model is developed for predicting the severity of stroke as measured by the
      National Institutes of Health Stroke Scale (NIHSS). The models were constructed
      by applying the Logical Analysis of Data (LAD) methodology to the mass peak
      profiles of 48 stroke patients and 32 controls. The classification model was
      shown to have an accuracy of 75% when tested on an independent validation set of
      35 stroke patients and 25 controls, while the predictive model exhibited superior
      performance when compared to alternative algorithms. In spite of their high
      accuracy, both models are extremely simple and were developed using a common set
      consisting of only 3 peaks. CONCLUSION: We have successfully identified 3
      biomarkers that can detect ischemic stroke with an accuracy of 75%. The
      performance of the classification model on the validation set and on cross
      validation does not deteriorate significantly when compared to that on the
      training set, indicating the robustness of the model. As in the case of the LAD
      classification model, the results of the predictive model validate the function
      constructed on our support-set for approximating the severity scores of stroke
      patients. The correlation and root mean absolute error of the LAD predictive
      model are consistently superior to those of the other algorithms used (Support
      vector machines, C4.5 decision trees, Logistic regression and Multilayer
      perceptron).

PMID- 18616826
TI  - Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in
      suboptimal oocyte maturation: a discussion of folate status, neural tube defects,
      schizophrenia, and vasculopathy.
AB  - Several conditions apparent at birth, e.g., neural tube defects (NTDs) and
      cardiac anomalies, are associated with polymorphisms in folate-related genes,
      such as the 677C --> T polymorphism of the methylenetetrahydrofolate reductase
      (MTHFR) gene. Similar associations have been established for several
      constitutional chronic diseases in adulthood, such as schizophrenia,
      cardiovascular diseases, dementia, and even neoplasias in different organ
      systems. This spectrum of developmental anomalies and constitutional diseases may
      be linked to high-risk conceptions related to preovulatory overripeness ovopathy
      (PrOO). Some developmental anomalies, such as NTDs, are to a large extent
      prevented by supplementation of folic acid before conception, but supplementation
      does not seem to prevent cardiovascular disease or cognitive decline. These
      diverging results can be elucidated by introduction of the PrOO concept, as MTHFR
      polymorphisms and inherent low folate levels induce both non-optimal maturation
      of the oocyte and unsuccessful DNA methylation and demethylation, i.e. epigenetic
      mutations. The PrOO concept is testable and predicts in a random population the
      following: (1) female carriers of specific genetic MTHFR variants exhibit more
      ovulatory disturbances and inherent subfecundity traits, (2) descendents from a
      carrier mother, when compared with those from a wild-type mother, are more
      frequently conceived in PrOO high-risk conditions and, thus, (3) disadvantaged in
      life expectancy. If so, some MTHFR polymorphisms represent a novel, genetically
      determined, PrOO high-risk conception category comparable to those which are
      environmentally and behaviorly influenced. These high-risk conditions may cause
      developmental anomalies and defective epigenetic reprogramming in progeny. The
      interaction between genetic and environmental factors is a plausible mechanism of
      multifactorial inheritance.

PMID- 18616827
TI  - MAID : an effect size based model for microarray data integration across
      laboratories and platforms.
AB  - BACKGROUND: Gene expression profiling has the potential to unravel molecular
      mechanisms behind gene regulation and identify gene targets for therapeutic
      interventions. As microarray technology matures, the number of microarray studies
      has increased, resulting in many different datasets available for any given
      disease. The increase in sensitivity and reliability of measurements of gene
      expression changes can be improved through a systematic integration of different
      microarray datasets that address the same or similar biological questions.
      RESULTS: Traditional effect size models can not be used to integrate array data
      that directly compare treatment to control samples expressed as log ratios of
      gene expressions. Here we extend the traditional effect size model to integrate
      as many array datasets as possible. The extended effect size model (MAID) can
      integrate any array datatype generated with either single or two channel arrays
      using either direct or indirect designs across different laboratories and
      platforms. The model uses two standardized indices, the standard effect size
      score for experiments with two groups of data, and a new standardized index that
      measures the difference in gene expression between treatment and control groups
      for one sample data with replicate arrays. The statistical significance of
      treatment effect across studies for each gene is determined by appropriate
      permutation methods depending on the type of data integrated. We apply our method
      to three different expression datasets from two different laboratories generated
      using three different array platforms and two different experimental designs. Our
      results indicate that the proposed integration model produces an increase in
      statistical power for identifying differentially expressed genes when integrating
      data across experiments and when compared to other integration models. We also
      show that genes found to be significant using our data integration method are of
      direct biological relevance to the three experiments integrated. CONCLUSION: High
      throughput genomics data provide a rich and complex source of information that
      could play a key role in deciphering intricate molecular networks behind disease.
      Here we propose an extension of the traditional effect size model to allow the
      integration of as many array experiments as possible with the aim of increasing
      the statistical power for identifying differentially expressed genes.

PMID- 18616828
TI  - Grammar-based distance in progressive multiple sequence alignment.
AB  - BACKGROUND: We propose a multiple sequence alignment (MSA) algorithm and compare
      the alignment-quality and execution-time of the proposed algorithm with that of
      existing algorithms. The proposed progressive alignment algorithm uses a grammar
      based distance metric to determine the order in which biological sequences are to
      be pairwise aligned. The progressive alignment occurs via pairwise aligning new
      sequences with an ensemble of the sequences previously aligned. RESULTS: The
      performance of the proposed algorithm is validated via comparison to popular
      progressive multiple alignment approaches, ClustalW and T-Coffee, and to the more
      recently developed algorithms MAFFT, MUSCLE, Kalign, and PSAlign using the
      BAliBASE 3.0 database of amino acid alignment files and a set of longer sequences
      generated by Rose software. The proposed algorithm has successfully built
      multiple alignments comparable to other programs with significant improvements in
      running time. The results are especially striking for large datasets. CONCLUSION:
      We introduce a computationally efficient progressive alignment algorithm using a
      grammar based sequence distance particularly useful in aligning large datasets.

PMID- 18616829
TI  - Monitoring of pre-frontal oxygen status in helicopter pilots using near-infrared
      spectrophotometers.
AB  - BACKGROUND: There are few in-flight studies of cognition-related cerebral oxygen
      status in helicopter pilots. METHODS: Four male helicopter pilots volunteered for
      nine sorties during visual flight in a BK117 and UH-60J. The pilots' pre-frontal
      oxy-hemoglobin (O2Hb) and deoxy-hemoglobin (HHb) concentration were continuously
      monitored from the right/left sections of the forehead using near-infrared
      spectrophotometers with a consideration of motion artifacts. RESULTS: The
      concentration of O2Hb progressively increased (13.98 micromol*L-1 as a maximum
      increased concentration) in both the right/left sections of the forehead from the
      basal level during the heightened cognitive demand of helicopter flight. There
      was comparatively little change (4.32 micromol*L-1 as a maximum increased
      concentration) in HHb concentration during measurement of helicopter flight. HHb
      changes were apparently not affected by a heightened cognitive demand of
      helicopter pilots. CONCLUSION: These results demonstrate that near-infrared
      spectroscopy, especially O2Hb measurements, provides a sensitive method for the
      monitoring of cognitive demand (maneuvers) in helicopter pilots.

PMID- 18616831
TI  - Epitope characterization of the protective monoclonal antibody VN04-2 shows
      broadly neutralizing activity against highly pathogenic H5N1.
AB  - The monoclonal antibody VN04-2 was previously shown to protect mice against
      lethal A/Vietnam/1203/04 H5N1 virus challenge when administered pre- and post
      infection. In this study, we characterized the binding requirements of this
      antibody using direct binding to hemagglutinin and neutralization assays with
      H5N1 virus-like particles (H5N1-VLP) of eight recent H5N1 strains representing
      the major mutations within the 140s antigenic loop. Binding was clade independent
      and 3 mutations within this antigenic region are required before escape is
      possible, suggesting that apart from the H5N1 viruses circulating in Indonesia,
      VN04-2 may provide protection against H5N1 viruses from all other regions.

PMID- 18616830
TI  - Low-intensity pulsed ultrasound activates the phosphatidylinositol 3 kinase/Akt
      pathway and stimulates the growth of chondrocytes in three-dimensional cultures:
      a basic science study.
AB  - INTRODUCTION: The effect of low-intensity pulsed ultrasound (LIPUS) on cell
      growth was examined in three-dimensional-cultured chondrocytes with a collagen
      sponge. To elucidate the mechanisms underlying the mechanical activation of
      chondrocytes, intracellular signaling pathways through the Ras/mitogen-activated
      protein kinase (MAPK) and the integrin/phosphatidylinositol 3 kinase (PI3K)/Akt
      pathways as well as proteins involved in proliferation of chondrocytes were
      examined in LIPUS-treated chondrocytes. METHODS: Articular cartilage tissue was
      obtained from the metatarso-phalangeal joints of freshly sacrificed pigs.
      Isolated chondrocytes mixed with collagen gel and culture medium composites were
      added to type-I collagen honeycomb sponges. Experimental cells were cultured with
      daily 20-minute exposures to LIPUS. The chondrocytes proliferated and a
      collagenous matrix was formed on the surface of the sponge. Cell counting,
      histological examinations, immunohistochemical analyses and western blotting
      analysis were performed. RESULTS: The rate of chondrocyte proliferation was
      slightly but significantly higher in the LIPUS group in comparison with the
      control group during the 2-week culture period. Western blot analysis showed
      intense staining of type-IX collagen, cyclin B1 and cyclin D1, phosphorylated
      focal adhesion kinase, and phosphorylated Akt in the LIPUS group in comparison
      with the control group. No differences were detected, however, in the MAPK,
      phosphorylated MAPK and type-II collagen levels. CONCLUSION: LIPUS promoted the
      proliferation of cultured chondrocytes and the production of type-IX collagen in
      a three-dimensional culture using a collagen sponge. In addition, the anabolic
      LIPUS signal transduction to the nucleus via the integrin/phosphatidylinositol 3
      OH kinase/Akt pathway rather than the integrin/MAPK pathway was generally
      associated with cell proliferation.

PMID- 18616832
TI  - Localization of hRad9 in breast cancer.
AB  - BACKGROUND: hRad9 is a cell cycle checkpoint gene that is up-regulated in breast
      cancer. We have previously shown that the mRNA up-regulation correlated with
      tumor size and local recurrence. Immunohistochemical studies were made to better
      define the role of hRad9 in breast carcinogenesis. METHODS: Localisation of hRad9
      protein were performed on paired tumor and normal breast tissues. Immunoblotting
      with and without dephosphorylation was used to define the protein isolated from
      breast cancer cells. RESULTS: Increased hRad9 protein was observed in breast
      cancer cells nucleus compared to non-tumor epithelium. This nuclear protein
      existed in hyperphosphorylated forms which may be those of the hRad9-hRad1-hHus1
      complex. CONCLUSION: Finding of hyperphosphorylated forms of hRad9 in the nucleus
      of cancer cells is in keeping with its function in ameliorating DNA instability,
      whereby it inadvertently assists tumor growth.

PMID- 18616833
TI  - Application of ecological momentary assessment in stress-related diseases.
AB  - Many physical diseases have been reported to be associated with psychosocial
      factors. In these diseases, assessment relies mainly on subjective symptoms in
      natural settings. Therefore, it is important to assess symptoms and/or
      relationships between psychosocial factors and symptoms in natural settings.
      Symptoms are usually assessed by self-report when patients visit their doctors.
      However, self-report by recall has an intrinsic problem; "recall bias". Recently,
      ecological momentary assessment (EMA) has been proposed as a reliable method to
      assess and record events and subjective symptoms as well as physiological and
      behavioral variables in natural settings. Although EMA is a useful method to
      assess stress-related diseases, it has not been fully acknowledged, especially by
      clinicians. Therefore, the present brief review introduces the application and
      future direction of EMA for the assessment and intervention for stress-related
      diseases.

PMID- 18616834
TI  - Articulation of three core metabolic processes in Arabidopsis: fatty acid
      biosynthesis, leucine catabolism and starch metabolism.
AB  - BACKGROUND: Elucidating metabolic network structures and functions in
      multicellular organisms is an emerging goal of functional genomics. We describe
      the co-expression network of three core metabolic processes in the genetic model
      plant Arabidopsis thaliana: fatty acid biosynthesis, starch metabolism and amino
      acid (leucine) catabolism. RESULTS: These co-expression networks form modules
      populated by genes coding for enzymes that represent the reactions generally
      considered to define each pathway. However, the modules also incorporate a wider
      set of genes that encode transporters, cofactor biosynthetic enzymes, precursor
      producing enzymes, and regulatory molecules. We tested experimentally the
      hypothesis that one of the genes tightly co-expressed with starch metabolism
      module, a putative kinase AtPERK10, will have a role in this process. Indeed,
      knockout lines of AtPERK10 have an altered starch accumulation. In addition, the
      co-expression data define a novel hierarchical transcript-level structure
      associated with catabolism, in which genes performing smaller, more specific
      tasks appear to be recruited into higher-order modules with a broader catabolic
      function. CONCLUSION: Each of these core metabolic pathways is structured as a
      module of co-expressed transcripts that co-accumulate over a wide range of
      environmental and genetic perturbations and developmental stages, and represent
      an expanded set of macromolecules associated with the common task of supporting
      the functionality of each metabolic pathway. As experimentally demonstrated, co
      expression analysis can provide a rich approach towards understanding gene
      function.

PMID- 18616835
TI  - Exhaustive identification of steady state cycles in large stoichiometric
      networks.
AB  - BACKGROUND: Identifying cyclic pathways in chemical reaction networks is
      important, because such cycles may indicate in silico violation of energy
      conservation, or the existence of feedback in vivo. Unfortunately, our ability to
      identify cycles in stoichiometric networks, such as signal transduction and
      genome-scale metabolic networks, has been hampered by the computational
      complexity of the methods currently used. RESULTS: We describe a new algorithm
      for the identification of cycles in stoichiometric networks, and we compare its
      performance to two others by exhaustively identifying the cycles contained in the
      genome-scale metabolic networks of H. pylori, M. barkeri, E. coli, and S.
      cerevisiae. Our algorithm can substantially decrease both the execution time and
      maximum memory usage in comparison to the two previous algorithms. CONCLUSION:
      The algorithm we describe improves our ability to study large, real-world,
      biochemical reaction networks, although additional methodological improvements
      are desirable.

PMID- 18616836
TI  - Hepatic metabolism of glucose and linoleic acid varies in relation to
      susceptibility to fatty liver in ad libitum-fed Muscovy and Pekin ducks.
AB  - The susceptibility to develop hepatic steatosis is known to differ between duck
      species, especially between Muscovy and Pekin ducks. This difference could be
      explained by either differential responses of species to overfeeding or genetic
      differences in hepatic lipid metabolism. The aim of the present study was to
      compare the intensities of the different hepatic pathways (oxidation,
      lipogenesis, esterification, secretion, etc.) of the two main nutrients (glucose
      and linoleic acid (LA)) reaching the liver of ad libitum-fed Muscovy (n 6) and
      Pekin (n 6) ducks using the ex vivo method of liver slices incubated for 16 h
      with [U-14C]glucose, [1-14C]LA and [35S]methionine added to the survival medium.
      In such experimental conditions, the lipogenesis pathway from glucose was 2-fold
      higher (P<0.05) in the liver of the Muscovy duck than in that of the Pekin duck.
      Furthermore, the hepatic uptake of LA was 2-fold higher (P<0.05) in the Muscovy
      duck than in the Pekin duck leading to a 2-fold higher (P<0.05) esterification of
      this fatty acid in the liver of the Muscovy duck. The hepatic secretion of VLDL
      was higher (P<0.01) in the Muscovy duck than in the Pekin duck but insufficient
      to prevent lipid accumulation in the liver of the Muscovy duck. In conclusion,
      these results show the influence of the species on the hepatic metabolism of
      ducks in relation to their susceptibility to develop fatty liver. These results
      should shed light on the metabolic regulations that might underlie susceptibility
      to hepatic steatosis in the the human liver.

PMID- 18616837
TI  - A novel method to remotely measure food intake of free-living individuals in real
      time: the remote food photography method.
AB  - The aim of the present study was to report the first reliability and validity
      tests of the remote food photography method (RFPM), which consists of camera
      enabled cell phones with data transfer capability. Participants take and transmit
      photographs of food selection and plate waste to researchers/clinicians for
      analysis. Following two pilot studies, adult participants (n 52; BMI 20-35 kg/m2
      inclusive) were randomly assigned to the dine-in or take-out group. Energy intake
      (EI) was measured for 3 d. The dine-in group ate lunch and dinner in the
      laboratory. The take-out group ate lunch in the laboratory and dinner in free
      living conditions (participants received a cooler with pre-weighed food that they
      returned the following morning). EI was measured with the RFPM and by directly
      weighing foods. The RFPM was tested in laboratory and free-living conditions.
      Reliability was tested over 3 d and validity was tested by comparing directly
      weighed EI to EI estimated with the RFPM using Bland-Altman analysis. The RFPM
      produced reliable EI estimates over 3 d in laboratory (r 0.62; P < 0.0001) and
      free-living (r 0.68; P < 0.0001) conditions. Weighed EI correlated highly with EI
      estimated with the RFPM in laboratory and free-living conditions (r>0.93; P <
      0.0001). In two laboratory-based validity tests, the RFPM underestimated EI by -
      4.7 % (P = 0.046) and - 5.5 % (P = 0.076). In free-living conditions, the RFPM
      underestimated EI by - 6.6 % (P = 0.017). Bias did not differ by body weight or
      age. The RFPM is a promising new method for accurately measuring the EI of free
      living individuals. Error associated with the method is small compared with self
      report methods.

PMID- 18616838
TI  - Echium oil is better than rapeseed oil in enriching poultry meat with n-3
      polyunsaturated fatty acids, including eicosapentaenoic acid and docosapentaenoic
      acid.
AB  - alpha-Linolenic acid (ALA; 18 : 3n-3) and stearidonic acid (SDA; 18 : 4n-3) are
      on the biosynthetic pathway of EPA (20 : 5n-3) and DHA (22 : 6n-3). The n-3 fatty
      acid in rapeseed oil is ALA while Echium oil contains both ALA and SDA. To
      determine the comparative efficacy of ALA- and SDA-rich oils in enriching broiler
      meat with n-3 PUFA, we offered diets supplemented with rapeseed oil (rapeseed
      group) or Echium oil (Echium group) for 35 d to two groups of chicks (age 21 d).
      There were no differences in carcass weight (2.20 (sem 0.06) v. 2.23 (sem 0.05)
      kg), boned, skinless thigh muscle (494 (sem 20.5) v. 507 (sem 16.7) g), boned,
      skinless breast muscle (553 (sem 13.4) v. 546 (sem 11.6) g) or organ weights
      (heart, liver and gizzard) between the two groups. The total intramuscular fat
      (IMF) percentage of thigh (8.0 (sem 0.64) v. 8.1 (sem 0.62) %) and breast muscles
      (2.3 (sem 0.24) v. 2.0 (sem 0.19) %) were also similar between the groups. In
      contrast, the concentrations of most of the individual n-3 fatty acids (ALA, SDA,
      EPA and docosapentaenoic acid) were all higher in the Echium than the rapeseed
      group (P < 0.05). However, differences in DHA concentrations were significant in
      breast but not thigh muscle IMF. The total n-3 yields/100 g serve thigh muscle
      were 265 and 676 mg for the rapeseed and Echium groups, respectively (P <
      0.0001). The corresponding values for equivalent breast muscles were 70 and 137
      mg, respectively (P < 0.01). We conclude that Echium oil is a better lipid
      supplement than rapeseed oil in changing the concentration and yield of n-3 fatty
      acids, except DHA, in broiler meat.

PMID- 18616839
TI  - Bioavailability of carotenoids and alpha-tocopherol from fruit juices in the
      presence of absorption modifiers: in vitro and in vivo assessment.
AB  - The food industry is playing an increasing role in the development and marketing
      of new products although little is known regarding the bioavailability of the
      phytochemicals they contain. Our aim was to assess the effect of the presence of
      absorption modifiers (milk and iron) on the in vitro bioaccessibility and the
      serum response in vivo of carotenoids and alpha-tocopherol from fruit juices.
      Thirty-two young women participated in a three-period (21 d each) supplementation
      study with a 2-week wash-out in between. Subjects consumed consecutively 2 x 250
      ml/d vitamin C-fortified juices supplied as fruit juice, fruit juice containing
      milk and fruit juice containing milk and iron. Fasting blood samples were
      collected before and after each supplementation period. In vitro bioaccessibility
      of carotenoids and alpha-tocopherol was assessed by a static digestion model.
      Vitamin E and carotenoids from both studies were determined by HPLC. In vitro,
      xanthophyll ester hydrolysis and transference of free xanthophylls and alpha
      tocopherol into the micellar phase were higher in the presence of absorption
      modifiers. In vivo, consumption of the fruit juices provoked significant
      increments (within-subject) of alpha-tocopherol and some carotenoids in serum.
      Dose-adjusted increments in serum of some carotenoids were higher when subjects
      consumed juices with milk and milk plus iron, although differences did not reach
      statistical significance. In conclusion, the presence of milk and milk plus iron
      do not influence the bioavailability of carotenoids and alpha-tocopherol from
      fruit juices in vivo. Our results support the use of in vitro models to assess
      food-related factors affecting bioavailability of carotenoids and tocopherols
      from foods.

PMID- 18616840
TI  - Ear, nose and throat manifestations of Behcet's disease: a review.
AB  - OBJECTIVE: To review Behcet's disease and to describe its clinical features in
      the head, neck and upper respiratory tract. METHOD: A literature review was
      undertaken, following a Medline search of publications over a 30-year period, and
      utilising the expert knowledge of one of the authors (RJM) with a specialist
      interest in Behcet's disease. RESULTS: Twenty-seven articles with ENT relevance
      were obtained. Otorhinolaryngological manifestations included symptoms and signs
      in the mouth, nose, sinus, larynx and ear. CONCLUSION: Behcet's disease is
      usually considered to be a condition affecting the oral cavity, eyes and
      genitals. This article shows that most patients will also exhibit other ENT
      symptoms, hearing loss in particular. Indeed, Behcet's disease may present with
      features other than the classic triad of symptoms. Raised awareness of the
      clinical features within the head and neck region will hopefully enable early
      diagnosis and treatment of this potentially serious condition.

PMID- 18616841
TI  - Familial Meniere's disease: clinical and genetic aspects.
AB  - BACKGROUND AND PURPOSE: Meniere's disease is not uncommon, with an incidence in
      Caucasians of about one in 2000. The incidence peaks in the fifth decade. Cases
      are usually isolated or sporadic, but in perhaps five per cent other family
      members are affected. We report here the clinical and genetic characteristics of
      a comprehensive set of familial Meniere's disease cases from the UK. METHODS:
      Forty-six affected families were studied. All cases were diagnosed using the
      American Academy of Otolaryngology-Head and Neck Surgery committee on hearing and
      equilibrium 1995, or more stringent, criteria. OUTCOMES AND RESULTS: Autosomal
      dominant inheritance with reduced penetrance was the most likely mode of
      inheritance overall. Apparent genetic anticipation was observed, but may also be
      a result of ascertainment bias given the collection strategy. There was also a
      slight tendency for cases to result from maternal transmission within the
      families in this set. The family pedigrees are presented, and the authors have
      also set up a website at which all the pedigrees may be viewed in greater detail.

PMID- 18616842
TI  - Oocyte activation procedures and influence of serum on porcine oocyte maturation
      and subsequent parthenogenetic and nuclear transfer embryo development.
AB  - The viability of SCNT embryos is poor, with an extremely low cloned piglet
      production rate. In the present work, we studied the effect of three activation
      protocols based on ionomycin treatment (5 microM ionomycin for 5 min and
      incubated in 2 mM 6-DMAP for 3.5 h) or electric stimuli (two square wave
      electrical DC pulses of 1.2 kV/cm for 30 micros) combined or not with 6-DMAP on
      parthenogenetic embryo development. Oocytes activated by ionomycin plus 6-DMAP
      showed lower cleavage (47.2 vs. 78.5-81.5; p < 0.05) and blastocyst rates (11.3
      vs. 29.2-32.1; p < 0.05) than those activated by electrical and electrical plus 6
      DMAP treatments. Also, we studied the effect of addition of serum to maturation
      medium (0% vs. 10%) on nuclear maturation and further parthenogenetic and SCNT
      embryo development. We observed in the parthenogenetic embryos that cleavage
      rates in the serum-free group were significantly higher than in the serum
      supplemented group (81.8 vs. 69.6% respectively; p < 0.05), although these
      differences were not detected in blastocyst rates or blastocyst nuclei numbers.
      Regarding SCNT embryos, no significant differences were observed in cleavage or
      blastocyst rates between different experimental groups of SCNT embryos. In
      conclusion, electrical pulse followed or not by 6-DMAP was found to be an
      efficient procedure to artificially activate MII porcine oocytes. Moreover, the
      addition of serum to oocyte maturation media did not seem to improve
      parthenogenetic or SCNT porcine embryo development.

PMID- 18616843
TI  - Primordial follicular assembly in humans--revisited.
AB  - Recent interest in the initial phases of ovarian follicular formation and
      development has lead to a number of publications in this area, most of which
      address the autocrine and paracrine factors involved in primordial follicle
      activation to primary follicle. Primordial follicle assembly (first step in
      follicle formation) determines the lifetime supply of primordial follicles and
      remains a poorly understood phenomenon. Despite a number of recent articles that
      are concentrating on immuno-histochemistry, basic steps in the process are not
      clear. Hence, we feel it is time to take a step back and see what is available in
      the literature and identify the gaps in which future research about primordial
      follicle assembly in humans needs to be directed.

PMID- 18616844
TI  - Activation of amphibian oocytes by sperm extracts.
AB  - In the fertilization of most animals, egg activation is accompanied by an
      increase in cytoplasmatic Ca2+; however, the mechanism through which the
      fertilizing sperm induce this phenomenon is still controversial. An increase in
      intracellular free Ca2+ is required to trigger egg activation events, a process
      that includes cortical granule exocytosis, resumption and completion of meiosis
      and DNA replication, and culminates in the first mitotic cleavage. In this work,
      we investigated the effect of microinjection and incubation of different
      fractions of homologous sperm extract on the activation of Bufo arenarum oocytes
      matured in vitro. Two heat treatment-sensitive fractions obtained by
      chromatography were able to induce oocyte activation. The sperm fraction, which
      contained a 24 kDa protein, induced 90% activation when it was microinjected into
      the oocytes. Whilst the sperm fraction, which contained a 36 kDa protein, was
      able to induce about 70% activation only when it was applied on the oocyte
      surface.

PMID- 18616845
TI  - Sex identification of pigs using polymerase chain reaction amplification of the
      amelogenin gene.
AB  - The amelogenin (AMEL) gene exists on both sex chromosomes of various mammalian
      species and the length and sequence of the noncoding regions differ between the
      two chromosome-specific alleles. Because both forms can be amplified using a
      single primer set, the use of AMEL in polymerase chain reaction (PCR)-based
      methods has facilitated sex identification in various mammalian species,
      including cattle, sheep and humans. In this study, we designed PCR primers to
      yield different-sized products from the AMEL genes on the X (AMELX) and Y (AMELY)
      chromosomes of pigs. PCR amplification of genomic DNA samples collected from
      various breeds of pigs (European breeds: Landrace, Large White, Duroc and
      Berkshire; Chinese breeds: Meishan and Jinhua and their crossbreeds) yielded the
      expected products. For all breeds, DNA from male pigs produced two bands (520 and
      350 bp; AMELX and AMELY, respectively), whereas samples from female pigs
      generated only the 520 bp product. We then tested the use of PCR of AMEL for sex
      identification of in vitro-produced (IVP) porcine embryos sampled at 2 or 5 to 6
      days after fertilization; germinal vesicle (GV)-stage oocytes and
      electroactivated embryos were used as controls. More than 88% of the GV-stage
      oocytes and electroactivated embryos yielded a single 520 bp single band and
      about 50% of the IVP embryos tested produced both bands. Our findings show that
      PCR analysis of the AMEL gene is reliable for sex identification of pigs and
      porcine embryos.

PMID- 18616846
TI  - Observation of the embryonic development in Pseudoplatystoma coruscans
      (Siluriformes: Pimelodidae) under light and scanning electron microscopy.
AB  - Pseudoplatystoma coruscans is a very popular species for tropical fish culture as
      it has boneless meat of delicate taste and firm texture. Few studies on fish
      reproductive biology refer to the morphological features of eggs. The goal,
      therefore, of this present work was to perform a structural and ultrastructural
      analysis of fertilization and embryonic development in P. coruscans. The
      incubation period, from fertilization to hatching, lasts 13 h at 28/29 degrees C
      and 18 h at 27 degrees C. The oocytes had a mean diameter of 0.95 mm and hatched
      larvae were 2.55 mm in diameter. Analysing their development, we observed round,
      yellow oocytes that bore a double chorion membrane and a single micropyle. At 10
      s after fertilization, several spermatozoa were detected attached to the oocyte
      surface. After 1 min of development, a fertilization cone that obstructed the
      micropyle could be observed. Segmentation started between 20 and 30 min after
      fertilization, when the egg cell was then formed. The first cleavage occurred
      between 30 and 45 min after fertilization, prior to reaching the morula stage (75
      and 90 min after fertilization). The epiboly movement started at 120 and 180 min
      after fertilization and ended at 360 and 480 min after fertilization.
      Differentiation between cephalic and caudal region was detected after 420 and 600
      min after fertilization and larvae hatched between 780 and 1080 min after
      fertilization. Seven main embryonic development stages were identified: egg cell,
      cleavage, morula, blastula, gastrula, segmentation with differentiation between
      cephalic and caudal regions, and hatching.

PMID- 18616847
TI  - Seasonal variation in food pattern but not in energy and nutrient intakes of
      rural Beninese school-aged children.
AB  - BACKGROUND: Inadequate energy and nutrient intakes are a major nutritional
      problem in developing countries. A recent study in Beninese school-aged children
      in different seasons revealed a high prevalence of stunting and poor iron status
      that might be related to the food pattern. OBJECTIVE: To analyse the food pattern
      and resulting energy and nutrient intakes of rural Beninese school-aged children
      in relation to season and school attendance. SUBJECTS AND METHODS: The study was
      performed in northern Benin in eighty randomly selected children aged 6-8 years.
      Dietary intake was assessed using observed weighed records. Food, energy and
      nutrient intakes were measured in post- and pre-harvest seasons. Complete food
      consumption data sets were available for seventy-five children. RESULTS: Food
      pattern showed seasonal variations. Cereals, roots and tubers were the main
      staple foods. Contributions of animal products to the diet were very small. The
      food pattern was not different for either boys v. girls or for children attending
      v. not attending school. Median daily energy intakes were 5.0 and 5.3 MJ in the
      post- and pre-harvest season, respectively. Only fat and vitamin C showed
      seasonal differences (P < 0.05). Energy and nutrient intakes were different for
      boys and girls but, unexpectedly, not for children attending v. not attending
      school. CONCLUSIONS: Seasonal variations in food pattern did not result in
      seasonality in energy and nutrient intakes. Because the children's diet was low
      in animal products, protein, fat and vitamin C and high in fibre, the absorption
      of fat, fat-soluble vitamins, carotenoids, Fe and Zn might be low. Fe and Zn
      bioavailability from such a diet needs further investigation.

PMID- 18616848
TI  - General parenting styles are not strongly associated with fruit and vegetable
      intake and social-environmental correlates among 11-year-old children in four
      countries in Europe.
AB  - OBJECTIVES: To investigate whether fruit and vegetable (F&V) intake in 11-year
      olds, and social-environmental correlates of F&V intake such as parental
      modelling and encouragement, family food rules and home availability, differ
      according to general parenting styles in Belgium, The Netherlands, Portugal and
      Spain. DESIGN: Cross-sectional study. SETTING: Primary schools in four countries.
      SUBJECTS: Pupils and one of their parents completed questionnaires to measure F&V
      intake, related social-environmental correlates and general parenting styles. The
      sample size was 4555 (49.3 % boys); 1180 for Belgium, 883 for The Netherlands,
      1515 for Portugal and 977 for Spain. Parenting styles were divided into
      authoritative, authoritarian, indulgent and neglectful. RESULTS: No differences
      were found in F&V intake across parenting styles and only very few significant
      differences in social-environmental correlates. The authoritarian (more parental
      encouragement and more demands to eat fruit) and the authoritative (more
      availability of fruit and vegetables) parenting styles resulted in more
      favourable correlates. CONCLUSION: Despite earlier studies suggesting that
      general parenting styles are associated with health behaviours in children, the
      present study suggests that this association is weak to non-existent for F&V
      intakes in four different European countries.

PMID- 18616849
TI  - Body size preference and body weight perception among two migrant groups of non
      Western origin.
AB  - OBJECTIVES: To evaluate body size preference, body weight perception and their
      relationship with actual weight in two migrant groups of non-Western origin,
      Turks and Moroccans; additionally, to study the association between body size
      preference and acculturation. DESIGN: Cross-sectional study. SETTING: Amsterdam,
      The Netherlands. SUBJECTS AND METHODS: Males and females (18-30 years) were
      randomly selected from the population registry (n 451); participants, or at least
      one of their parents, were born in Turkey or Morocco. Body size preference was
      assessed using seven silhouette drawings and body weight perception was assessed
      by asking participants' opinion of own weight. Acculturation variables were
      generation status and two scale measures, cultural orientation and social
      contacts. RESULTS: Participants showed preference for a thin body size. The
      discrepancy between ideal and current size was significant in women but not men
      (P < 0.001). Perceived current body size was correlated with BMI (Spearman's
      correlation coefficient 0.60, P < 0.001 (men) and 0.73, P < 0.001 (women)). Among
      overweight participants (BMI = 25.0-29.9 kg/m2), 63-82 % of men and 35 % of women
      perceived themselves as 'average'. Paying attention to own body weight was
      associated with a discrepancy between ideal and current size among women and with
      perceiving oneself as 'overweight' among men. Body size preference was not
      significantly associated with the three acculturation variables. CONCLUSION: We
      did not observe a preference for large body sizes in these two non-Western
      migrant groups. Similar to Western populations, most women wished to be thinner
      than they were. This was not the case among men, the majority of whom were also
      unaware of being overweight.

PMID- 18616850
TI  - Dietary habits mediate the relationship between socio-economic status and CVD
      factors among healthy adults: the ATTICA study.
AB  - BACKGROUND: The aims of the present work were to investigate whether dietary
      habits are associated with socio-economic status (SES), and if they modify the
      relationship between SES and CVD risk factors, in a sample of men and women free
      from known CVD. METHODS: This population-based study was carried out in the
      province of Attica, where Athens is a major metropolis. During 2001-2002,
      information from 1,528 men (18-87 years old) and 1,514 women (18-89 years old)
      was collected (75 % participation rate). Among several sociodemographic, clinical
      and biological factors, adherence to the Mediterranean diet was assessed by a
      special diet score (Mediterranean Diet Score, MDS) that incorporated the inherent
      characteristics of this traditional diet. CVD risk factors were examined across
      the participants' educational level and annual income that defined their SES.
      RESULTS: Low SES groups exhibited higher prevalence of CVD risk factors, such as
      obesity, hypertension, diabetes mellitus and hypercholesterolaemia (all P <
      0.001). Low SES groups also showed less adherence to the Mediterranean diet than
      high SES groups (MDS: 23.6 (sd 8.1) v. 25.6 (sd 5.6), P < 0.001). Higher SES
      index was associated with lower likelihood of having hypercholesterolaemia (OR =
      0.91; 95 % CI 0.83, 1.00) and diabetes (OR = 0.83; 95 % CI 0.72, 0.95), after
      adjusting for various potential confounders. However, the previously mentioned
      inverse relationship observed between SES and prevalence of CVD risk factors was
      mainly explained by the dietary habits of the participants. CONCLUSIONS: Low SES
      groups showed less adherence to the Mediterranean diet compared with high SES
      groups. This finding may, in part, explain the higher CVD risk factors profile
      observed among low SES participants.

PMID- 18616851
TI  - Identifying 'unhealthy' food advertising on television: a case study applying the
      UK Nutrient Profile model.
AB  - OBJECTIVES: To evaluate the feasibility of the UK Nutrient Profile (NP) model for
      identifying 'unhealthy' food advertisements using a case study of New Zealand
      television advertisements. DESIGN: Four weeks of weekday television from 15.30
      hours to 18.30 hours was videotaped from a state-owned (free-to-air) television
      channel popular with children. Food advertisements were identified and their
      nutritional information collected in accordance with the requirements of the NP
      model. Nutrient information was obtained from a variety of sources including food
      labels, company websites and a national nutritional database. RESULTS: From the
      60 h sample of weekday afternoon television, there were 1893 advertisements, of
      which 483 were for food products or retailers. After applying the NP model, 66 %
      of these were classified as advertising high-fat, high-salt and high-sugar (HFSS)
      foods; 28 % were classified as advertising non-HFSS foods; and the remaining 2 %
      were unclassifiable. More than half (53 %) of the HFSS food advertisements were
      for 'mixed meal' items promoted by major fast-food franchises. The advertising of
      non-HFSS food was sparse, covering a narrow range of food groups, with no
      advertisements for fresh fruit or vegetables. CONCLUSIONS: Despite the NP model
      having some design limitations in classifying real-world televised food
      advertisements, it was easily applied to this sample and could clearly identify
      HFSS products. Policy makers who do not wish to completely restrict food
      advertising to children outright should consider using this NP model for
      regulating food advertising.

PMID- 18616852
TI  - Preconceptional folic acid supplement use in Lebanon.
AB  - OBJECTIVE: The objective of the present study was to assess the prevalence and
      determinants of preconceptional folic acid supplement use among pregnant women in
      Lebanon. DESIGN/SETTING/SUBJECTS: The study was a descriptive epidemiological
      study. Analysis was performed on 5280 deliveries admitted to twelve member
      hospitals of the National Collaborative Perinatal Neonatal Network during the
      period September 2003-January 2005. Information on folic acid intake and maternal
      and neonatal characteristics were obtained from obstetric charts along with
      direct interviews performed by trained personnel. Logistic regression was
      performed to determine the predictors of preconceptional folic acid use. RESULTS:
      The overall use of preconceptional folic acid supplementation was 14.0 % (18.6 %
      in urban hospitals v. 2.7 % in rural hospitals). Higher socio-economic status,
      lower parity and having a history of previous spontaneous abortions were
      significantly associated with preconceptional folic acid use. CONCLUSION: Our
      study shows that Lebanon currently has a low rate of preconceptional folic acid
      supplement use. Intervention through the means of awareness campaigns needs to be
      implemented on a national level.

PMID- 18616853
TI  - Memory changes in normal and pathological aging.

PMID- 18616854
TI  - Aging and memory: a cognitive approach.
AB  - This article describes changes in memory during the normal aging process from the
      standpoint of cognitive psychology. There is now a great deal of evidence to show
      that memory is not one single function but may be described in terms of different
      memory systems that show differential effects of aging. For example, memory for
      procedures, and some perceptual memory functions, show few age-related changes,
      whereas working memory, episodic memory, and prospective memory decline
      substantially in the course of normal aging. Memory for facts and knowledge
      (semantic memory) holds up well in older individuals provided that the
      information is used frequently, although the ability to retrieve highly specific
      information (such as names) typically declines. The article discusses current
      theoretical accounts of the effects of aging; different theorists have attributed
      the changes in memory and cognition to mental slowing, declining attentional
      resources, an inability to inhibit unwanted information, and a decline in
      cognitive control. Other suggestions include the notion that memory performance
      in older adults is particularly vulnerable when the need for self-initiated
      processing is greatest; conversely, performance is greatly helped by the
      provision of environmental support. The practical implications of these research
      findings and ideas include the point that clinical memory assessments should
      incorporate tests designed to measure the different aspects of memory
      functioning.

PMID- 18616855
TI  - Memory and cognition in preclinical dementia: what we know and what we do not
      know.
AB  - This overview focuses on the cognitive transition between normal aging and
      dementia. Numerous studies indicate that individuals who will go on to develop
      dementia show cognitive deficits many years before the time at which a clinical
      diagnosis could be rendered. The degree of preclinical impairment is remarkably
      similar for tasks assessing episodic memory, executive functioning, and
      perceptual speed, consistent with the view that multiple brain alterations occur
      prior to clinical disease onset. Although most research in this area has dealt
      with Alzheimer disease (AD), several recent reports indicate that the pattern of
      preclinical impairment is very similar in the second largest dementia disorder,
      vascular dementia (VaD). This is important because currently the possibility for
      interventions to postpone disease onset is greater in VaD than in AD. Despite
      pronounced preclinical cognitive deficits in dementia, the performance
      distributions between cases and controls are largely overlapping, hampering the
      ability to identify high-risk individuals. To alleviate this problem, future
      research should evaluate hybrid models for the prediction of dementia. In such
      models, multiple indicators of cognitive functioning should be included along
      with markers from other domains that have been linked to subsequent dementia
      (such as brain imaging, genetics, and lifestyle variables). To the extent that
      these categories of variables add unique variance, classification accuracy will
      increase and the overlap in performance scores between incident cases and
      controls will decrease, thereby enhancing clinical usefulness. This approach
      would also facilitate the examination of interactive effects among classes of
      preclinical markers.

PMID- 18616856
TI  - Personality and differential treatment response in major depression: a randomized
      controlled trial comparing cognitive-behavioural therapy and pharmacotherapy.
AB  - OBJECTIVE: Effective treatments for major depressive disorder exist, yet some
      patients fail to respond, or achieve only partial response. One approach to
      optimizing treatment success is to identify which patients are more likely to
      respond best to which treatments. The objective of this investigation was to
      determine if patient personality characteristics are predictive of response to
      either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). METHOD:
      Depressed patients completed the Revised NEO Personality Inventory, which
      measures the higher-order domain and lower-order facet traits of the Five-Factor
      Model of Personality, and were randomized to receive either CBT or PHT. RESULT:
      Four personality traits--the higher-order domain neuroticism and 3 lower-order
      facet traits: trust, straightforwardness, and tendermindedness--were able to
      distinguish a differential response rate to CBT, compared with PHT. CONCLUSION:
      The assessment of patient dimensional personality traits can assist in the
      selection and optimization of treatment response for depressed patients.

PMID- 18616857
TI  - Work characteristics and social phobia in a nationally representative employed
      sample.
AB  - OBJECTIVE: Social phobia is associated with long-term impairment and disability.
      Environmental and genetic influences may be important in etiology and
      persistence. This is the first study to examine the association of work
      characteristics with social phobia in a representative nationally employed
      population. METHOD: Self-reported work characteristics were linked to 12-month
      social phobia diagnosed by the World Mental Health Composite International
      Diagnostic Interview in 24 324 employed individuals from the Canadian Community
      Health Survey. RESULTS: High job strain (OR = 1.62, 95%CI, 1.06 to 2.49) and job
      insecurity (OR = 2.47, 95%CI, 1.73 to 3.51) were associated with an increased
      risk of 12-month social phobia, adjusting for sociodemographic variables,
      prevalent depression, and other work characteristics. CONCLUSIONS: Work
      characteristics are associated with social phobia. Characteristics such as job
      insecurity may be a consequence of illness in employed populations, while high
      job strain may increase the risk of symptoms. More investigation is needed of the
      relation between work and social phobia to understand how to reduce occupational
      disability.

PMID- 18616858
TI  - Contact of mental and nonmental health care providers prior to suicide in Taiwan:
      a population-based study.
AB  - OBJECTIVE: Higher rates of health care service use prior to suicide were
      previously reported in Western countries; however, these studies have tended to
      suffer from small sample sizes. This nationwide, population-based study examines
      the distribution and patterns of health care service use among suicide victims in
      Taiwan. METHOD: A retrospective cohort study was conducted using linked
      population-based data to determine the proportion of health care service use
      among suicide victims aged 15 years and older within the 1-year and 1-month
      period prior to their deaths. After adjusting for demographic, socioeconomic and
      health care indices, the differences in health care service use patterns were
      assessed for age and sex. RESULTS: Among the 19 426 suicide victims in the
      sample, 83.1% had used nonmental health care services within the 1-year period
      prior to their death, while only 22.2% had used mental health care services. Men,
      and suicide victims aged 55 years and older, were less likely to have had any
      contact with mental health care professionals prior to their deaths (P < 0.001).
      CONCLUSIONS: In line with prior studies, similarly high rates and distinct
      patterns of health care service use were found in Taiwan prior to suicide. These
      findings will be of practical interest and should support designing appropriate
      methods of suicide intervention and effective preventive strategies.

PMID- 18616859
TI  - Predictive validity of the psychopathy checklist: screening version for
      intramural behaviour in violent offenders-a prospective study at a secure
      psychiatric hospital in Germany.
AB  - OBJECTIVE: To consider the extent to which the presence of psychopathy, as
      indicated by the psychopathy checklist: screening version (PCL:SV), can predict
      intramural behaviour in offenders with mental disorders serving compulsory
      treatment at a German forensic psychiatric hospital. METHOD: The PCL:SV was used
      with 48 offenders detained at a forensic psychiatric hospital in Germany. In a
      prospective design, objective and subjective measures of behaviour were compared
      for those identified as high and low scorers on the PCL:SV. Data were obtained
      from hospital records of disciplinary incidents (objective) and from interviews
      with case managers and therapists (subjective), according to predefined criteria
      and in standardized forms. RESULTS: The hospital records of the high scorers
      indicated they had been involved in significantly more disciplinary incidents
      than low scorers. Their behaviour was also rated significantly more negative by
      therapists than the low scorers. CONCLUSION: Numeorus studies found the
      psychopathy checklist (PCL) score to be a reliable predictor of recidivism in
      offenders after release. The present study has demonstrated that the PCL score
      has also predictive validity for intramural behaviour problems in individuals
      serving compulsory treatment at a forensic psychiatric hospital. As a result, we
      recommend the routine use of the PCL with offenders starting a period of
      compulsory detention to identify those at increased risk for problem behaviour.

PMID- 18616860
TI  - Mathematical learning disorder in school-age children with attention-deficit
      hyperactivity disorder.
AB  - OBJECTIVES: To explore the prevalence of mathematics disorder (MD) relative to
      reading disorders (RD) in school-age children with attention-deficit
      hyperactivity disorder (ADHD) and examine the effects of age, sex, cooccurring
      conduct disorder (CD), and ADHD subtype on this comorbidity. METHODS:
      Participants were school-age children (n = 476) with confirmed DSM-IV diagnosis
      of ADHD. The assessment included semistructured parent and teacher interviews and
      standardized measures of intelligence, academic attainment, and language
      abilities. Based on the presence or absence of concurrent learning disorders, we
      compared the emerging 4 groups: ADHD-only, ADHD + MD, ADHD + RD, and ADHD + MD +
      RD. RESULTS: Overall prevalence of comorbid ADHD + MD was 18.1%. Age, sex, ADHD
      subtypes, or comorbid CD did not affect the frequency of MD. Children with
      concurrent ADHD and either MD or RD attained lower IQ, language, and academic
      scores than those with ADHD alone. Children with ADHD + MD + RD were more
      seriously impaired and demonstrated distinct deficits in receptive and expressive
      language. CONCLUSION: MDs are relatively common in school-age children with ADHD
      and are frequently associated with RDs. Children with ADHD + MD + RD are more
      severely impaired. These deficits simply cannot be explained as consequences of
      ADHD and might have unique biological underpinnings, with implications for
      diagnostic classification and therapeutic interventions.

PMID- 18616861
TI  - Effect of olanzapine and risperidone on subjective well-being and craving for
      cannabis in patients with schizophrenia or related disorders: a double-blind
      randomized controlled trial.
AB  - OBJECTIVE: To examine whether subjective well-being and craving for cannabis were
      different in patients with schizophrenia or related disorders treated with either
      olanzapine or risperidone. METHOD: A 6-week, double-blind, randomized trial of
      olanzapine and risperidone was carried out in 128 young adults with recent onset
      schizophrenia or related disorders. Primary efficacy measures were the mean
      baseline-to-endpoint change in total scores on the Subjective Well-Being under
      Neuroleptics scale, the Obsessive-Compulsive Drug Use Scale, the Drug Desire
      Questionnaire, and the cannabis use self-report. An analysis of covariance was
      used to test between-group differences. RESULTS: Estimated D(2) receptor
      occupancy did not differ between olanzapine (n = 63) and risperidone (n = 65).
      Similar improvements in subjective well-being were found in both groups. In the
      comorbid cannabis-using group (n = 41, 32%), a similar decrease in craving for
      cannabis was found in both treatment conditions. CONCLUSIONS: Both olanzapine and
      risperidone were associated with improved subjective well-being. No evidence was
      found for a differential effect of olanzapine or risperidone on subjective
      experience or on craving for cannabis in dosages leading to comparable dopamine
      D(2) occupancy. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN46365995.

PMID- 18616862
TI  - Re: new developments in cognitive-behavioural therapy for mood disorders.

PMID- 18616863
TI  - Prescribing patterns in hypertension: the emerging role of fixed-dose
      combinations for attaining BP goals in hypertensive patients.
AB  - BACKGROUND: The attainment of clinical blood pressure (BP) goals can markedly
      reduce cardiovascular morbidity and mortality, yet approximately two-thirds of
      treated hypertensive patients in the United States have uncontrolled BP.
      Consequently, more aggressive management of hypertension, frequently involving
      combination therapy (e.g., fixed-dose combination [FDC] therapy), is needed to
      achieve the recommended BP goals of <140/90 mmHg for most patients, and <130/80
      mmHg for high-risk patients. SCOPE: This article, based on data from an extensive
      Medline search ('hypertension' AND 'prescribe', 'prescribing' OR 'prescription',
      date range: 1995-2007), focuses on prescribing patterns for antihypertensive
      medication, and on the emerging role of combination therapy, specifically FDC
      therapy, in treating hypertensive patients to target BP levels. FINDINGS:
      Although the use of antihypertensive combination therapy has increased
      substantially in US adults over the last 20 years, such therapy remains
      considerably underutilized. Numerous studies have shown that combination
      therapies, including FDCs, can markedly reduce BP and adverse events relative to
      monotherapies, and this paper overviews data for various combination therapies:
      angiotensin-receptor blocker (ARB) + diuretic; angiotensin-converting enzyme
      (ACE) inhibitor + diuretic; calcium-channel blocker (CCB) + ACE inhibitor; and
      CCB + ARB. Specifically, fixed-dose CCB/ARB combinations of amlodipine with
      losartan, valsartan, or olmesartan medoxomil have recently been developed, and
      combination therapy schedules of amlodipine plus one of these ARBs have shown
      greater BP-lowering efficacy compared with the constituent monotherapies.
      Furthermore, in two large studies in a total of >3000 patients, CCB + ARB
      combination therapy was associated with significantly lower incidences of
      headache and peripheral edema than CCB monotherapy. CONCLUSION: Guidelines for
      hypertension management clearly support the greater use of multidrug therapy,
      especially in high-risk patients. FDCs (e.g., various emerging CCB/ARB
      combinations) are a valuable option for such high-risk patients, as these
      combinations offer the potential to reduce adverse events, increase compliance,
      lower treatment costs, and improve BP goal-attainment rates.

PMID- 18616864
TI  - Obesity, disease burden, and prescription spending by community-dwelling Medicare
      beneficiaries.
AB  - OBJECTIVES: To assess drug utilization and cost patterns by body mass index (BMI)
      for Medicare beneficiaries including cohorts diagnosed with diseases resulting
      from, or aggravated by, obesity. RESEARCH DESIGN: We used data from the 2003
      Medicare Current Beneficiary Survey to characterize the community-dwelling
      Medicare population by BMI class and to assess the following outcomes: (1)
      prevalence of drugs recommended in treating obesity-related chronic diseases, (2)
      annual spending on these medications by disease cohort, and (3) spending for all
      medications for the full study sample. Linear regression techniques were used to
      assess the conditional association of BMI class with drug spending controlling
      for sociodemographic characteristics, prescription drug coverage, health status,
      and comorbidities. RESULTS: Annual drug spending in 2003 was significantly higher
      (p < 0.05) for obese class I ($2374) and class III ($2976) compared to normal
      weight beneficiaries ($1764). Obese individuals also had higher utilization rates
      for selected medications used to treat diabetes, hypertension, ischemic heart
      disease, heart failure, hyperlipidemia, and osteoarthritis. Regression results
      indicate that chronic disease is the main reason why drug spending is higher
      among the obese, but prescription drug coverage is also a significant factor.
      CONCLUSIONS: Obesity is associated with significantly higher drug spending among
      Medicare beneficiaries. The combination of growing numbers of obese
      beneficiaries, high rates of chronic disease, and greater than average
      prescription spending per condition will all contribute to higher future Part D
      and overall Medicare program costs. Limitations of the study include: self
      reported data on height, weight, and drug use/spending; small sample size; and
      pre-Part D data.

PMID- 18616865
TI  - Depletion of intracellular zinc down-regulates expression of Uch-L1 mRNA and
      protein, and CREB mRNA in cultured hippocampal neurons.
AB  - Zinc deficiency has been associated with impaired learning and memory function in
      animals and human beings. However, the molecular mechanisms remain obscure. In
      light of evidence that ubiquitin C-terminal hydrolase L1 (Uch-L1) and cAMP
      responsive element-binding protein (CREB) are required for synaptic and memory
      function and the possible regulation of CREB by Uch-L1, this present study was
      conducted to investigate the effect of zinc depletion on Uch-L1 protein
      expression and on Uch-L1 and CREB mRNA expression in cultured hippocampal
      neurons. Cultured hippocampal neurons were exposed to a cell membrane-permeant
      zinc chelator TPEN (2 microM), and to TPEN plus zinc sulphate (5 microM) for 24
      h. Cultures were then processed to detect neuronal injury by lactate
      dehydrogenase (LDH) assay, Uch-L1 protein levels by Western blot, and Uch-L1 and
      CREB mRNAs levels by RT-PCR. The LDH release rate in TPEN-incubated neurons was
      notably increased compared to non-treated controls. Significant down-regulation
      of Uch-L1 protein level and mRNA levels for Uch-L1 and CREB were observed in TPEN
      treated neurons. Co-addition of zinc almost completely reversed TPEN-induced
      neuronal injury and the alterations in Uch-L1 and CREB expression. The results
      demonstrated that zinc modulated the expression of Uch-L1 and CREB at the protein
      and/or transcription levels in hippocampal neurons, which implies that down
      regulation of both Uch-L1 and CREB might participate in memory dysfunction
      induced by zinc deficiency.

PMID- 18616866
TI  - Influence of phosphatidylserine on cognitive performance and cortical activity
      after induced stress.
AB  - The aim of this study was to investigate the effect of phosphatidylserine (PS) on
      cognition and cortical activity after mental stress. After familiarization, 16
      healthy subjects completed cognitive tasks after induced stress in a test-re-test
      design (T1 and T2). Directly after T1, subjects were assigned double-blind to
      either PS or placebo groups followed by T2 after 42 days. At T1 and T2, cortical
      activity was measured at baseline and immediately after stress with cognitive
      tasks using electro-encephalography (EEG). EEG was recorded at 17 electrode
      positions and fast Fourier transforms (FFT) determined power at Theta, Alpha-1,
      Alpha-2, Beta-1 and Beta-2. Statistics were calculated using ANOVA (group x trial
      x time). The main finding of the study was that chronic supplementation of
      phosphatidylserine significantly decreases Beta-1 power in right hemispheric
      frontal brain regions (F8; P < 0.05) before and after induced stress. The results
      for Beta-1 power in the PS group were connected to a more relaxed state compared
      to the controls.

PMID- 18616867
TI  - Brain endocannabinoid system is involved in fluoxetine-induced anorexia.
AB  - In order to describe the effects of chronic fluoxetine administration on the
      brain endocannabinoid system in lean and obese Zucker rats, brain immunostaining
      for the CB1 and CB1-phosphorylated cannabinoid receptors was carried out. Obese
      Zucker rats showed significantly increased the numbers of neural cells positively
      immunostained for the CB1-phosphorylated receptor in the striatum, compared to
      their lean litter-mates. Chronic fluoxetine administration decreased the number
      of neural cells immunostained for CB1-phosphorylated receptor in several striatal
      and hippocampal regions of obese Zucker rats, compared to controls treated with
      saline. In contrast, no change in CB1-phosphorylated receptor immunostaining was
      observed in fluoxetine-treated lean rats, with respect to controls. Taken
      together, these results suggest the involvement of the hippocampal and striatal
      endocannabinoid receptor system in fluoxetine-induced anorexia in lean and obese
      Zucker rats.

PMID- 18616868
TI  - Brain fatty acid profiles and spatial learning in malnourished rats: effects of
      nutritional intervention.
AB  - The aim of the present study was to determine the effects of malnutrition and
      nutritional rehabilitation on learning and memory performance and brain fatty
      acid composition. Pregnant and lactating Wistar rats were either fed ad libitum
      on a commercial laboratory chow or a multideficient diet from north-eastern
      Brazil (regional basic diet; RBD). After weaning, RBD offspring either continued
      on the multideficient diet (malnourished group) or switched to a control diet
      (rehabilitated group), until day 70. There was no difference in the passive
      avoidance test among the experimental groups, but malnourished rats showed
      important deficits in performance of the Morris water maze which were improved in
      the rehabilitated group. The hippocampus and cerebellum of the malnourished rats
      showed important changes in fatty acid profile obtained by gas-liquid
      chromatography, but the rehabilitated group had decreased n-3 polyunsaturated
      fatty acids and an increase in the proportion of arachidonic acid. The data
      suggest that nutritional rehabilitation results in partial restoration of fatty
      acid profiles and cognitive performance.

PMID- 18616869
TI  - Mini Nutritional Assessment in patients with Parkinson's disease: correlation
      between worsening of the malnutrition and increasing number of disease-years.
AB  - OBJECTIVE: To monitor the nutritional status of patients with Parkinson's disease
      using the Mini Nutritional Assessment (MNA) questionnaire. PATIENTS AND METHODS:
      This was a 3-year longitudinal study conducted in a national referral centre for
      Parkinson's disease and other movement disorders. The cohort included 61
      Parkinson's disease patients, 37 men and 24 women, mean age of 70.5 +/- 5.5
      years, mean duration of disease 9 +/- 6.3 years; 35 patients were followed-up
      after 3 years. RESULTS: MNA score diminished from 24.9 +/- 1.6 to 24 +/- 2.5 (P =
      0.02); the proportion of patients at risk of malnutrition increased from 22.9% to
      34.3%. A linear correlation was observed between MNA score and the duration of
      disease (P = 0.0096). The dietary assessment subscore significantly diminished
      (8.6 versus 8.1; P = 0.0009) as did body mass index (25.9 +/- 3.5 kg/m(2) versus
      27.1 +/- 3.1 kg/m(2); P = 0.001). CONCLUSIONS: The evaluation of nutritional
      status should be part of the routine work-up of a Parkinson's disease patient.
      Dietary education should be included amongst the therapeutic measures designed to
      improve the general conditions in Parkinson's disease.

PMID- 18616870
TI  - Perspectives from the symposium: The role of nutrition in infant and toddler
      brain and behavioral development.
AB  - This symposium examined current trends in neuroscience and developmental
      psychology as they apply to assessing the effects of nutrients on brain and
      behavioral development of 0-6-year-olds. Although the spectrum of nutrients with
      brain effects has not changed much in the last 25 years, there has been an
      explosion in new knowledge about the genetics, structure and function of the
      brain. This has helped to link the brain mechanistic pathway by which these
      nutrients act with cognitive functions. A clear example of this is linking of
      brain structural changes due to hypoglycemia versus hyperglycemia with cognitive
      functions by using magnetic resonance imaging (MRI) to assess changes in brain
      region volumes in combination with cognitive test of intelligence, memory and
      processing speed. Another example is the use of event-related potential (ERP)
      studies to show that infants of diabetic mothers have impairments in memory from
      birth through 8 months of age that are consistent with alterations in mechanistic
      pathways of memory observed in animal models of perinatal iron deficiency.
      However, gaps remain in the understanding of how nutrients and neurotrophic
      factors interact with each other in optimizing brain development and function.

PMID- 18616871
TI  - High prevalence of arterial thrombosis in JAK2 mutated essential
      thrombocythaemia: independence of the V617F allele burden.
AB  - Approximately half of the patients with essential thrombocythaemia (ET) harbor
      the JAK2 V617F mutation. Despite a phenotypic mimicry of JAK2 V617F positive ET
      and polycythaemia vera (PV), the data on thromboembolic risk and correlation to
      JAK2 mutation status are ambiguous. On a strictly WHO defined ET cohort we
      evaluated possible clinical correlations to the JAK2 mutation status including a
      history of previous thrombosis. We used a highly sensitive quantitative real-time
      PCR (qPCR) assay for JAK2 V617F detection and allele burden quantification in a
      single institution study of 55 patients. A significantly increased prevalence of
      arterial thrombosis was recorded in JAK2 positive ET (p=0.001). There was no
      association between the mutational load and thrombosis. As compared to their JAK2
      V617F negative counterparts, the JAK2 V617F positive patients had PV-like
      biochemical characteristics such as higher haemoglobin levels (p=0.02), lower
      platelet counts (p=0.002) and lower plasma EPO levels (p=0.04). The JAK2 V617F
      mutation per se but not the mutational load in patients with ET is associated
      with a PV-like phenotype and a higher prevalence of previous arterial thrombosis.
      This study adds further support to the contention of the JAK2 V617F mutation as a
      marker of increased risk of thrombosis.

PMID- 18616872
TI  - Long-term efficacy of oral deferiprone in management of iron overload in beta
      thalassemia major.
AB  - OBJECTIVE: Variable response to deferiprone has been observed in the management
      of iron overload in patients with thalassemia major. Our objective was to assess
      the long-term efficacy of deferiprone in patients with thalassemia major.
      METHODS: We analyzed the serum ferritin levels in fifty-eight patients who were
      on deferiprone therapy for at least three years. We divided patients into three
      groups based on the initial serum ferritin level: group 1, <2000 ng/ml; group 2,
      2000-4000 ng/ml; group 3, <4000 ng/ml. RESULTS: Repeated measurement analysis
      showed a fall in serum ferritin level in group 3 after 12 months but again
      increased after 24 months, whereas other groups showed an increase in serum
      ferritin after 12 months which was sustained for 3 years. The patients were
      divided into three groups depending on the comparison of serum ferritin at the
      beginning and at the end; response group I: patients remained in the same
      ferritin group (n=30), response group II: patients progressed to more severe
      group (n=17), response group III: serum ferritin decreased and patient shifted to
      the lower group of ferritin level (n=11). Comparing various factors which could
      affect the response to deferiprone among three groups, no factor other than serum
      ferritin at the beginning of the treatment showed significant effect. However,
      some patients with a serum ferritin value in the lower range also showed
      improvement. CONCLUSION: The major factor determining the response to deferiprone
      was initial serum ferritin. But some patients responded well even with relatively
      low initial serum ferritin.

PMID- 18616873
TI  - Osteomyelosclerosis with thalassemia trait: report of a rare association, study
      of platelet function tests and review of literature.
AB  - Idiopathic myelofibrosis is a chronic myeloproliferative disorder characterized
      by excessive connective tissue deposition in the bone marrow. It presents with
      leucoerythroblastic anemia and massive splenomegaly. It is termed
      osteomyelosclerosis in the presence of primitive bone formation in the bone
      marrow and radiological presence of osteosclerosis. A 40-year-old male, known
      case of thalassemia trait presented with fatigue and lump in the abdomen for two
      months. Physical examination showed splenomegaly 8.5 cm below costal margin. X
      ray examination revealed multiple osteosclerotic lesions involving the pelvis and
      long bones. Hemogram showed: hemoglobin 7.8 gm/dl, TLC 47,500/mm(3); DLC was
      polymorphs 49%, lymphocytes 7%, eosinophils 4%, basophils 4%, blasts 5%,
      promyelocytes 2%, myelocytes 14%, metamyelocytes 10%. Platelet count was
      60,000/mm(3). Peripheral blood film showed leucoerythroblastic blood picture with
      features of dysmyelopoiesis. Bone marrow aspiration was diluted with peripheral
      blood. Bone marrow biopsy showed replacement of marrow by grade III reticulin
      fibrosis. Bony trabaculae were wide and thick. Platelet function studies were
      abnormal. The clinical, radiological and hematological features suggested a
      diagnosis of osteomyelosclerosis. We present this case because no similar
      association of osteomyelosclerosis with thalassemia trait has been described in
      English literature to date. This is the first study from India, which describes
      platelet function tests in a patient with osteomyelosclerosis.

PMID- 18616874
TI  - Spectrum of pure red cell aplasia in adult population of north-west India.
AB  - Pure red cell aplasia (PRCA) is a rare haematological disorder characterised by
      selective inhibition of red cell precursors in the bone marrow. We conducted a
      retrospective analysis of nine cases of PRCA seen in our adult haematology clinic
      from January 2000 to December 2003. All patients had baseline hemogram, bone
      marrow examination, CT scan of chest, autoimmune and infectious disease markers.
      The diagnosis of PRCA was made on bone marrow examination showing normal
      granulocytic and megakaryocytic series with erythroblastopenia. The age range was
      14-68 years (median: 40 years) and a male to female ratio of 3 : 1. In five
      patients, the aetiology of PRCA could not be identified with available
      investigations and were labelled as primary PRCA. The secondary causes of PRCA
      included three cases of thymoma and one case of non-Hodgkin lymphoma. Out of nine
      patients, three patients had died and two lost to follow-up. At the last
      available follow-up till December 2006, three patients (one secondary and two
      primary PRCA) are maintaining normal haemoglobin and one patient still has active
      disease. The retrospective review shows that causes and outcome of PRCA in the
      developing world are different to those seen in the West.

PMID- 18616875
TI  - Tissue chimerism analysis after donor lymphocyte infusion: a case of deceptive
      evidence.
AB  - A 31-year-old female with refractory extramedullary myeloid leukemia relapse
      underwent peripheral blood stem-cell transplantation from her HLA-identical
      brother. Hematopoietic recovery followed disappearance of the lesions. Studies
      three-months post-transplant showed complete chimerism (CC). Fourteen months
      after transplantation, the patient presented with an increasing number of
      extramedullary sites of biopsy-proven disease relapse (as nodular skin lesions).
      Bone marrow was in remission with maintenance of CC. However, tissue chimerism
      analysis showed full recipient-cell population. After one course of conventional
      dose chemotherapy followed by mobilized donor-lymphocyte infusions (DLI), a
      complete response was achieved. DLI continued monthly but she developed new skin
      lesions accompanied by multiple cervical masses. Bone marrow and tissue chimerism
      revealed both recipient and donor cell population. We conclude that tissue
      chimerism analysis after DLI may not accurately document the cell origin.

PMID- 18616876
TI  - Elevated serum endostatin levels are associated with favorable outcome in acute
      myeloid leukemia.
AB  - BACKGROUND: Endostatin is the C-terminal antiangiogenic fragment of the
      extracellular matrix protein collagen XVIII, and is generated by tumor-derived
      proteases. The levels and the prognostic relevance of serum endostatin in acute
      myeloid leukaemia (AML) patient are not fully clear. OBJECTIVE: The aim of this
      study was to evaluate serum levels of endostatin in acute myeloid leukemia
      patients before chemotherapy and after achieving complete remission and to
      correlate endostatin levels with patient outcome. MATERIALS AND METHODS: Serum
      samples from 30 adult patients (22 males and eight females, median age 37, range
      19-66 years) with AML had been taken before chemotherapy was administered. In
      addition 25 out of 30 patients were reinvestigated again at complete remission
      (CR). Ten samples from healthy normal persons of matched age and sex were
      evaluated as a reference control group. Serum endostatin levels were determined
      using enzyme linked immune sorbent assay (ELISA). Endostatin serum levels were
      not significantly different in the pre-treatment AML patients as compared to that
      in normal controls (p>0.05). In AML patients the baseline endostatin levels were
      significantly lower than at CR (p=0.001). RESULTS: No significant relation were
      detected between pre-treatment serum endostatin levels and age, peripheral blood
      white cell counts, platelet counts, bone marrow blast cell counts, blast cell
      distribution ratio or cytogenetic findings. The prognostic value of serum
      endostatin (sE) was also evaluated by dividing AML patients into high and low sE
      groups using the 75 percentile sE levels of the patients group as cutoff. The
      authors found that patients group in the high sE group survived for significantly
      longer time than those patients in the low sE group. CONCLUSION: Elevated
      endostatin levels at AML diagnosis is a good prognostic marker for patients'
      outcome. Wide scale study is recommended in order to establish the clinical value
      of this study.

PMID- 18616877
TI  - Leukemic infiltration of the breast in acute lymphocytic leukemia (ALL).
AB  - Extramedullary leukemic infiltration of the breast in adult acute lymphocytic
      leukemia (ALL) is rare. We report two such cases here. One patient died of
      relapsed ALL and the other was cured with local radiation therapy and remains
      alive and in remission 30 years after relapsing in her breast. A literature
      review of reported cases of ALL with breast involvement is discussed.

PMID- 18616878
TI  - Modified IDARAM chemotherapy regimen for primary central nervous system lymphoma:
      experience of three cases.
AB  - The use of radiotherapy (RT) with chemotherapy has improved disease free survival
      and control in primary central nervous system lymphoma (PCNSL). We have
      encountered three patients with histologically documented central nervous system
      lymphoma. In all patients pathological diagnosis was B-cell lymphoma. We modified
      IDARAM regimen to R-IDARAM to enhance and optimize chemotherapeutic components
      for the treatment of PCNSL. We made three changes: (i) we added rituximab 375
      mg/m(2) day 1; (ii) increased dose of MTX from 2 to 3 g/m(2); and (iii)
      administered two additional courses of R-IDARAM after cranial RT. Following
      complete staging after course 2, radiotherapy was applied at a dosage of 3600
      4140 cGy in conventional schedule (180 or 200 cGy per day) to whole brain (with
      3600 cGy to eyes in one case because of eye involvement) and then 2 additional
      courses of R-IDARAM (totally four courses) chemotherapy regimen were applied.
      Complete remission (CR) was achieved after first two cycles of R-IDARAM in
      patient 1 and 3 and after four cycles in patient 2. Currently, three patients
      have been alive for 29, 10, 15 months respectively. Currently there is no
      standard treatment modality for PCNSL. Increased dosage of MTX, adding rituximab
      and consolidation of the IDARAM to R-IDARAM regimen may improve disease control
      and outcome in PCNSL patients.

PMID- 18616879
TI  - Detection of Epstein-Barr virus in children and adolescents with Burkitt's
      lymphoma by in situ hybridization using tissue microarrays.
AB  - In this retrospective study, we evaluated 53 patients diagnosed with Burkitt's
      lymphoma (BL). Patients were admitted to the Pediatric Department of Santa Casa
      de Sao Paulo, Brazil from August 1988 to September 2006. The male gender was
      found more frequently in the proportion of three males to one female. At the time
      of the diagnosis, the mean age was 6 years. The most frequent clinical
      presentation was abdominal (extra nodal) in 42 (79.2%) cases. The patients were
      treated with chemotherapy using two different treatment methods, 30 cases until
      September 1994 with BGLTI -87 and the other 23 until September of 2006 with BGLTI
      -96. According to Murphy's classification, 90.2% of the patients were diagnosed
      as stages III and VI showing an advanced disease at time of diagnosis. Using
      Tissue Microarrays (TMA); we searched for the expression of the Epstein-Barr
      virus (EBV) RNA in 50 patients. The presence of EBV using in situ hybridization
      was found in 33/50 (66%) and there was no association between the presence of the
      virus in the tumor cells or patient age, as well as the survival rate. There was
      74.5% global survival rate until September, 2005 of 12 years and 8 months. The
      disease free survival rate was 86.5%. The frequency of the EBV association with
      this neoplasia in Brazil is intermediate between the endemic and sporadic forms
      of disease.

PMID- 18616880
TI  - The outcome of haemopoietic stem cell transplantation in the treatment of
      lymphoplasmacytic lymphoma in the UK: a British Society Bone Marrow
      Transplantation study.
AB  - Lymphoplasmacytic lymphoma (LL) is incurable by standard therapy (median
      survival: 60 months). UK transplant registry data 1984-2003 identified 18 cases
      of histologically verified LL (median age: 50 years, range: 38-58 years). Nine
      patients received high dose chemotherapy [plus total body irradiation (TBI) in
      1/9] and autologous peripheral blood stem cells (PBSC). Disease status at
      transplant was complete remission (2), partial remission (5), primary refractory
      (1) or relapse (1). Transplant related mortality (TRM) at 12 months was 0%.
      Median follow-up is 44 months with 4 year disease free survival 43% and overall
      survival 73%. Karnofsky performance status (KPS) is 80-100%. The nine allografted
      patients (median age: 49 years, range: 39-56 years) were conditioned with
      standard TBI (2), BEAM (2) or FLU-MEL (5) and received PBSC from HLA-matched
      sibling (8) or unrelated (1) donors. Disease status at transplant was partial
      remission (7) or primary refractory (2). TRM at 12 months was 44%. Complications
      included graft failure (2), grades I-II acute graft versus host disease (aGVHD)
      (2), grades III-IV aGVHD (3) and chronic GVHD (4). Median follow-up is 32 months
      with 4 year disease free survival 44% and overall survival 56%. KPS is 70-100%.

PMID- 18616881
TI  - Diagnosis of multiple myeloma using enzyme immunoassay for detection of
      antibodies to N-acetyl glucosamine on microparticles.
AB  - Immunoassay on polymeric particles with covalently bound N-acetyl glucosamine was
      applied for detection of appropriate antibodies. Antibodies to N-acetyl
      glucosamine were detected in sera of patients with multiple myeloma. The assay
      was conducted on polymeric microparticles by enzyme immunoassay. The
      sensitivities of the assays on microparticles and on glass microtubes were
      compared. It was shown that the level of antibodies to N-acetyl glucosamine
      correlated with the number of myeloma cells. The comparison of assays on
      microparticles and glass tubes demonstrate the advantage of microparticle
      technology.

PMID- 18616882
TI  - The need for a father: mixed messages in the UK's new legislation on gamete
      donors?

PMID- 18616884
TI  - Relevance of basal serum FSH to IVF outcome varies with patient age.
AB  - Live birth rate (LBR), age and basal serum FSH values were analysed in 1589 women
      undergoing their first cycle of IVF. Four age groups (<30, 30-34, 35-38, 39-45
      years) and three FSH groups (<5, 5-9.9, > or =10 IU/l) were established. Logistic
      regression analysis was used to determine the effect of age and FSH on live
      birth. A model to predict the probability of a live birth suggests that an
      additional 10 years of age reduces the odds for live birth (OR = 0.66, 95% CI
      0.48-0.91); an increase of FSH by 5 IU/l reduces the probability of live birth
      (OR = 0.75, 95% CI 0.61-0.92); women > or =39 years have an additional reduction
      in probability of live birth (OR = 0.58, 95% CI 0.61-0.92). Analysis by age and
      FSH categories showed that pregnancy rate (PR) did not change significantly with
      rising FSH for women <35 years old. In cycles started with serum FSH <5 IU/l,
      increasing age did not effect PR and LBR. Cycles started with serum FSH > or =10
      IU/l had a PR and LBR of 23.6 and 16.9% respectively. The clinical relevance of
      elevated FSH varies according to age; younger women with elevated FSH and older
      women with low FSH still have an acceptable LBR.

PMID- 18616885
TI  - Ovulation induction with tamoxifen and alternate-day gonadotrophin in patients
      with thin endometrium.
AB  - Tamoxifen has been reported to be oestrogenic on the lower genital tract. To
      evaluate its potential positive effect on the endometrium, and consequently early
      miscarriage and ongoing pregnancy rate, a prospective study was employed in
      patients for intrauterine insemination who failed to develop an adequate
      endometrial thickness in a previous ovulatory cycle. Ovarian stimulation was
      initiated with tamoxifen 40 mg/day from day 3 of the menstrual cycle for 7 days
      or clomiphene 100 mg/day for 5 days, in combination with 150 IU of human
      menopausal gonadotrophin on alternate days starting on day 4. Human chorionic
      gonadotrophin (HCG) was administered when at least one leading follicle was
      larger than 20 mm. Intrauterine insemination was accomplished 24-36 h after HCG
      injection and luteal phase supplement was achieved with micronized progesterone
      200 mg transvaginally per day. It was found that tamoxifen-treated patients
      required more stimulation days and used more gonadotrophin, but recruited less
      follicles larger than 14 mm than clomiphene-treated patients. However, a
      significantly increased endometrial thickness (P < 0.001) and pregnancy rate (P =
      0.015), decreased early miscarriage rate (P = 0.001) and thus improved ongoing
      pregnancy (P < 0.001) rate were noted in tamoxifen-treated patients. These
      results suggest that although tamoxifen may not be a first-line treatment in
      patients with adequate endometrium, it may be a promising alternative for
      patients with thin endometrium.

PMID- 18616886
TI  - Molecular analysis of mutations and polymorphisms in the CFTR gene in male
      infertility.
AB  - Mutations of the cystic fibrosis transmembrane regulator (CFTR) gene and
      polymorphisms, such as the (TG)m and Tn polymorphic loci in intron 8 at the
      splice acceptor site of exon 9, can cause male infertility. The aim of this study
      was to investigate the frequency of the most prevalent cystic-fibrosis-causing
      mutations, the IVS8-Tn alleles and IVS8-TG12 variant in the presence of IVS8-5T
      in patients with altered semen parameters (group I with obstructive azoospermia,
      group II with secretory azoospermia and group III with severe oligozoospermia)
      compared with a control group with normozoospermia. CFTR mutations were found in
      26.5% and 14.3% of chromosomes of patients of group I and II respectively (P <
      0.001, P < 0.05). The frequency of the 5T allele was 23.5% in patients in group I
      (P < 0.01), and was linked exclusively with TG12 allele. The present study
      reports for the first time a high proportion of the 5T allele in patients in
      group III (9.2%, P < 0.05). These results underline the importance of performing
      molecular analysis of mutations and IVS8-Tn polymorphism in the CFTR gene and
      appropriate genetic counselling to all couples undergoing assisted reproductive
      technologies when the partner has azoospermia or severe oligozoospermia.

PMID- 18616887
TI  - ERCC1 and ERCC2 polymorphisms and risk of idiopathic azoospermia in a Chinese
      population.
AB  - The ERCC1 (excision repair cross complementation group 1) and ERCC2 (excision
      repair cross complementation group 2) genes are important in repairing DNA damage
      and genomic instability in germ cells, and are essential for normal
      spermatogenesis. It has been verified that polymorphisms of these two genes could
      alter DNA repair capacity in some phenotypic studies. However, little information
      is available on these polymorphisms in male infertility. This study was designed
      to examine whether ERCC1 polymorphisms 3 UTR (C8092A), Asn118Asn (G19007A) and
      ERCC2 polymorphisms Asp312Asn (G-->A), Lys751Gln (A-->C), which have been
      reported to contribute to some cancers, are associated with idiopathic
      azoospermia in the Chinese population. The four polymorphisms were genotyped
      using polymerase chain reaction-restriction fragment length polymorphism assay in
      a hospital-based case-control study, comprising 202 infertile patients with
      idiopathic azoospermia and 187 fertile controls. It was found that the ERCC1 8092
      CA + AA genotypes were significantly associated with an increased risk of
      idiopathic azoospermia (OR = 1.750, 95% CI = 1.170-2.618), while other
      polymorphisms appeared to show no significant differences between cases and
      controls. Further studies are needed to confirm the roles of these polymorphisms
      in idiopathic azoospermia.

PMID- 18616888
TI  - Significance of large nuclear vacuoles in human spermatozoa: implications for
      ICSI.
AB  - The aim of this study was to determine the extent of DNA fragmentation and the
      presence of denatured single-stranded or normal double-stranded DNA in
      spermatozoa with large nuclear vacuoles (LNV) selected by high magnification.
      Fresh semen samples from 30 patients were prepared by discontinuous isolate
      concentration gradient. Spermatozoa with normal nucleus (NN) and LNV were
      selected at x8400 magnification and placed on different slides. DNA fragmentation
      was determined by TUNEL assay. Denatured and double-stranded DNA was identified
      by the acridine orange fluorescence method. DNA fragmentation in spermatozoa with
      LNV (29.1%) was significantly higher (P < 0.001) than in spermatozoa with NN
      (15.9%). Therefore, cleavage of genomic DNA in low molecular weight DNA fragments
      (mono- and oligonucleosomes), and single-strand breaks (nicks) in high molecular
      weight DNA occur more frequently in spermatozoa with LNV. Similarly, the
      percentage of denatured-stranded DNA in spermatozoa with LNV (67.9%) was
      significantly higher (P < 0.0001) than in spermatozoa with NN (33.1%). The high
      level of denatured DNA in spermatozoa with LNV suggests precocious decondensation
      and disaggregation of sperm chromatin fibres. The results show an association
      between LNV and DNA damage in spermatozoa, and support the routine morphological
      selection and injection of motile spermatozoa at high magnification for ICSI.

PMID- 18616889
TI  - Comparison of ICSI and conventional IVF in patients with increased oocyte
      immaturity.
AB  - Using sibling oocytes, the objective of this study was to compare the
      intracytoplasmic sperm injection (ICSI) fertilization rates to those achieved
      with conventional IVF in patients with high rates of oocyte immaturity. This
      study was observational in nature, and included 91 patients who were treated
      using split insemination techniques. The fertilization rates for the ICSI group
      and the IVF group were 41.1 +/- 15.0% and 53.2 +/- 19.8%, respectively (P &lt:
      0.0001). There was no significant difference in day-3 embryo quality between the
      two groups. There was a significantly higher number of embryos frozen in the IVF
      group than in the ICSI group: 357 (84.8%) and 297 (76.7%), respectively (P =
      0.037). Furthermore, the number of embryos either transferred or frozen was
      significantly higher in the IVF group than the ICSI group: 459 of 1173 (39.1%)
      and 385 of 1268 (30.4%), respectively (P < 0.0001). These data indicate that
      conventional IVF results in a higher fertilization rate than ICSI. Furthermore,
      IVF provided more embryos available for transfer or cryopreservation when
      compared with ICSI, thereby optimizing the patient's cycle.

PMID- 18616891
TI  - Birth and follow-up of babies born following ICSI using SrCl2 oocyte activation.
AB  - This report describes six successful pregnancies (five healthy children from four
      deliveries and two miscarriages) with SrC1(2) oocyte activation using spermatozoa
      from nine patients with repeated fertilization failure. Oocytes were artificially
      activated by SrC1(2) 30 min after intracytoplasmic sperm injection (ICSI).
      Oocytes were placed in 10 mmol/l of SrC1(2) medium for 1 h, rinsed several times,
      and then cultured in Universal IVF medium. Developmental characteristics of five
      resulting children until 1 year old were assessed according to the maternal and
      children health hand book issued by Mothers' and Children's Health Organization
      in Japan. Mean fertilization rate, mean frequency of good cleaved embryos,
      pregnancy rate, and implantation rate after artificial activation in nine couples
      were increased from 21.7 to 64.5% (P < 0.001), from 0 to 15.4%, from 0 to 40.0%
      and from 0 to 25.0% respectively. Five healthy children were born following ICSI
      and artificial activation between February 2005 and March 2006. Physical and
      mental development of the children from birth to 12 months was normal. These
      suggest the utility and safety of SrCl(2) for patients with repeated failed
      fertilizations following ICSI and artificial activation.

PMID- 18616892
TI  - Comparison of in-vitro maturation cycles with and without in-vivo matured oocytes
      retrieved.
AB  - This study compared the embryological characteristics and clinical outcome of in
      vitro maturation (IVM) treatment cycles with and without in-vivo matured oocytes
      collected following human chorionic gonadotrophin (HCG) priming. The patients
      were administered 10,000 IU of HCG subcutaneously when endometrial thickness
      reached > or =6 mm and oocyte collection was performed 35-36 h after HCG
      administration. The clinical outcome and embryological aspects were analysed
      between IVM cycles with (group 1) and without (group 2) in-vivo matured oocytes.
      In group 1, three (range 1-12) in-vivo matured oocytes per patient were retrieved
      on average. The number of good quality embryos derived from in-vivo matured
      oocytes in group 1 was significantly higher than those derived from in-vitro
      matured oocytes in group 1 and group 2 (P < 0.05). However, there was no
      difference between the number of good quality embryos produced from in-vitro
      matured oocytes in the two groups. There were 12 clinical pregnancies (40.0%) in
      group 1, and seven pregnancies (23.3%) in group 2. These results suggest that IVM
      cycles with in-vivo matured oocytes resulted in a good clinical pregnancy rate,
      which could be explained by the superior quality of embryos derived from the in
      vivo matured oocytes.

PMID- 18616893
TI  - New options in assisted reproduction technology: the Cryotop method of oocyte
      vitrification.
AB  - The Cryotop vitrification method has been shown to be a very useful tool for
      oocyte cryopreservation, giving excellent results regarding survival and clinical
      outcome. There are several clinical situations in which oocyte cryopreservation
      provides solutions that have not been available to date. This report describes
      three of these situations: (i) a low-responder patient who needed a single gene
      diagnosis due to the presence of a genetic disease; (ii) a patient undergoing
      endometrial bleeding on the day of oocyte retrieval who was also affected by a
      genetic disorder; and (iii) a patient who failed to become pregnant after the
      donation of vitrified oocytes and subsequently had the re-vitrified surplus
      embryos transferred. The resolution of these cases provides evidence of the
      enormous potential of the Cryotop method as a tool within assisted reproduction
      technology.

PMID- 18616894
TI  - The Well-of-the-Well system: an efficient approach to improve embryo development.
AB  - Transfer of human embryos at the blastocyst stage may offer considerable benefits
      including an increased implantation rate and a decreased risk of multiple
      pregnancies; however, blastocyst culture requires an efficient and reliable in
      vitro embryo culture system. In this study, the effect of the Well-of-the-Well
      (WOW) system consisting of microwells formed on the bottom of the culture dish
      was tested in three mammalian species, including humans. The WOW system resulted
      in significant improvement when comparing the drops for culture of in-vitro
      matured and parthenogenetically activated porcine oocytes, and in-vivo-derived
      mouse zygotes. In human embryos, using a sibling oocyte design, embryos cultured
      in WOW developed to the blastocyst stage in a significantly higher proportion
      than did embryos cultured traditionally (55% in WOW and 37% in conventional
      culture; P < 0.05). In a separate study, also in human, a total of 48 patients
      with a cumulative 214 unsuccessful previous IVF cycles were selected for the
      trials. In subsequent intracytoplasmic sperm injection cycles, oocytes/embryos
      were cultured individually in the WOW system or in microdrops. Transferable
      quality blastocyst development (48.9% of cultured zygotes) was observed in the
      WOW system. Ninety-four blastocysts transferred to 45 patients resulted in
      clinical pregnancy rates of 48.9%, including nine twin pregnancies, seven single
      pregnancies, five miscarriages and one ectopic pregnancy. The results indicate
      that the WOW system provides a promising alternative for microdrop culture of
      mammalian embryos, including human embryos.

PMID- 18616895
TI  - Elective single embryo transfer versus double embryo transfer in assisted
      reproduction.
AB  - High numbers of embryos transferred during assisted reproduction have become
      implicated as the cause of higher than normal twinning and multiple gestation
      rates following this form of therapy. However, reducing the number to a single
      embryo transferred has been shown to carry unfavourable results in the first
      cycle, but with similar cumulative live birth rates. This study tested the theory
      by performing a randomized controlled trial of elective single embryo transfer
      (SET) versus double embryo transfer (DET) in young women, and follow them up for
      1 year to determine the result of cryo-embryo transfer cycles in the two cohorts.
      The results showed that the probability of a live birth was not significantly
      different between the two groups, but with a higher rate of twins in the DET
      group. In addition, during the 1-year follow-up period, the live birth, clinical
      pregnancy and multiple pregnancy rates were also similar, and in line with the
      results of the randomized trial. In conclusion, the results of this prospective
      randomized trial and 1-year follow-up show that in young women, elective SET
      should be the first line of choice. Even so, these results should be confirmed by
      larger randomized studies.

PMID- 18616896
TI  - Implantation, clinical pregnancy and miscarriage rates after introduction of
      ultrasound-guided embryo transfer.
AB  - The purpose of this study was to compare the reproductive outcome of ultrasound
      guided (USG) embryo transfers versus clinical touch embryo transfers. A
      statistically powered retrospective analysis of women undergoing fresh and frozen
      embryo transfers in a National Health Service-based tertiary referral centre in
      the Department of Reproductive Medicine, St Mary's Hospital, Manchester was
      carried out. A total of 1723 embryo transfers were included in the analysis. The
      implantation rate was significantly higher in the USG embryo transfer group
      compared with the non-USG embryo transfer group (fresh: 19.9 versus 9.5%, P <
      0.0001; frozen: 13.1 versus 7.3%, P < 0.0004). The clinical pregnancy rate was
      also significantly higher in the former group (fresh: 26.9 versus 12.5%, P <
      0.0001; frozen: 15.6 versus 8.9%, P < 0.0015). For the frozen embryos, the
      miscarriage rate was significantly elevated among the USG embryo transfer group
      [unadjusted rate ratio (RR) = 1.65, 95% CI: 1.04, 2.62], but this was of
      borderline significance when the model was adjusted for the potential confounders
      (adjusted RR = 1.56, 95% CI: 0.997, 2.45). There was no difference in the ectopic
      pregnancy rates between the two groups. The findings of this study show that the
      practice of USG embryo transfer is associated with statistically higher
      implantation and clinical pregnancy rates in IVF.

PMID- 18616897
TI  - Recipient age and pulsatility index affect uterine receptivity in oocyte donation
      programmes.
AB  - Successful embryo implantation depends on interactions between the embryo and the
      uterus. Investigating factors related to the recipients in an oocyte donation
      programme could therefore improve the overall pregnancy outcome. In this study,
      the factors that affect outcomes following IVF after oocyte donation were
      evaluated in a retrospective cohort study. A total of 143 cycles were evaluated.
      All oocyte donors were younger than 30 years of age. In the youngest recipients
      (< 34 years old) the implantation rate was higher (P = 0.042) and the abortion
      rate was apparently lower than in the recipients of more advanced age (> or =40
      years old). The implantation and pregnancy rates were higher when the pulsatility
      index was > or = 3.0. The pulsatility index on the day of embryo transfer in
      oocyte donation IVF cycles was an important determinant of successful pregnancy
      outcomes.

PMID- 18616898
TI  - Early risk factors for miscarriage: a prospective cohort study in pregnant women.
AB  - Many pregnancies are lost during early gestation, but clinicians still lack tools
      to recognize risk factors for miscarriage. Thus, the identification of risk
      factors for miscarriage during the first trimester in women with no obvious risk
      for a pregnancy loss was the aim of this prospective cohort trial. A total of
      1098 women between gestation weeks 4 and 12 in whom no apparent signs of a
      threatened pregnancy could be diagnosed were recruited. Demographic, anamnestic,
      psychometric and biological data were documented at recruitment and pregnancy
      outcomes were registered subsequently. Among the cases with sufficiently
      available data, 809 successfully progressing pregnancies and 55 subsequent
      miscarriages were reported. In this cohort, risk of miscarriage was significantly
      increased in women at higher age (>33 years), lower body mass index (< or =20 kg/
      m(2)) and lower serum progesterone concentrations (< or =12 ng/ml) prior to the
      onset of the miscarriage. Women with subsequent miscarriage also perceived higher
      levels of stress/demands (supported by higher concentrations of corticotrophin
      releasing hormone) and revealed reduced concentrations of progesterone-induced
      blocking factor. These risk factors were even more pronounced in the subcohort of
      women (n = 335) recruited between gestation weeks 4 and 7. The identification of
      these risk factors and development of an interaction model of these factors, as
      introduced in this article, will help clinicians to recognize pregnant women who
      require extra monitoring and who might benefit from therapeutic interventions
      such as progestogen supplementation, especially during the first weeks of
      pregnancy, to prevent a miscarriage.

PMID- 18616899
TI  - Mechanisms behind flare of renal lupus during murine pregnancy.
AB  - The outcome of pregnancy in systemic lupus erythematosus is still controversial.
      The authors recently reported the disappearance of the manifestation of the skin
      disease but a diminished survival rate in lupus-prone animals undergoing several
      pregnancies. It was postulated that lupus-prone animals must have subclinical
      renal symptoms at an early age and that immune and hormonal changes during
      pregnancy exacerbate immune reactions in the kidneys, leading to a shortened life
      span. Here, the authors analysed changes at day 14 of pregnancy in lupus-prone
      LPR (MRL/lpr) mice and MRL controls regarding cytokines, regulatory T (Treg)
      cells and deposition of immunocomplexes. Worsened kidney function was observed
      during pregnancy, even in the absence of lupus signs. This was accompanied by
      renal inflammation and higher interferon-gamma and interleukin-10 levels. C3 and
      immunoglobulin G deposition was enhanced in kidney and placenta from lupus-prone
      pregnant animals. Pregnancy enhanced the levels of Treg cells in control animals
      but not in lupus-prone animals. As pregnancy-induced Treg cells were shown to be
      specific for paternal antigens it is not to be expected that these Treg cells can
      help to destroy autoreactive cells. The authors conclude that early subclinical
      kidney disease in lupus-prone animals exacerbates during pregnancy. Albeit
      obtained with an experimental animal model, their data are potentially of
      importance for lupus patients of reproductive age.

PMID- 18616900
TI  - Efficient method for slow cryopreservation of human embryonic stem cells in xeno
      free conditions.
AB  - An effective, consistent and xeno-free cryopreservation technique is crucial for
      any human embryonic stem cell (hESC) laboratory with future perspectives for
      clinical application. This study presents a new slow freezing-rapid thawing
      method in serum-free conditions that allows the cryopreservation of a large
      number of colonies without the use of a programmable freezer. To test its
      efficacy, this method has been compared with two established vitrification
      methods and applied to three different hESC lines (H9, VAL-3 and VAL-5). The
      method is based on an increasing concentration of dimethylsulphoxide (1.0, 1.2,
      1.5 and 2.0 mol/l) with a slow or a rapid cooling system. Using this method,
      approximately 60 colonies per cryovial could be cryopreserved, the survival rate
      ranged between 15 and 68% depending on the cell line used, and the majority of
      the surviving colonies were grade A. Post-cryopreserved hESC have been cultured
      for 20 passages, re-cryopreserved and re-thawed with consistent results. After
      thawing, cells retained the inherent undifferentiated characteristics of hESC and
      growth rate curve, with a stable karyotype, telomerase activity and teratoma
      formation when injected into severe combined immunodeficient animals, which was
      comparable with the fresh lines. This method has been tested for 3 years in two
      different laboratories.

PMID- 18616902
TI  - Preservation of fertility in young cancer patients: contribution of transmission
      electron microscopy.
AB  - During the last decade, new technologies in reproductive medicine have emerged to
      preserve the fertility of women whose gonadal function is threatened by premature
      menopause or gonadotoxic treatments. To offer an individualized approach to these
      patients, different experimental procedures are under investigation, including
      oocyte cryopreservation and cryopreservation and transplantation of ovarian
      tissue in the form of cortical fragments, whole ovary or isolated follicles. This
      review shows that transmission electron microscopy (TEM), combined with other in
      vivo and in-vitro analysis techniques, is a valuable tool in the establishment of
      new experimental protocols to preserve female fertility. Ultrastructural studies
      allow in-depth evaluation of the oocyte's unique morpho-functional
      characteristics, which explain its low cryotolerance, and provide essential
      information on follicular, stromal and endothelial cell integrity, as well as
      cellular interactions crucial for normal folliculogenesis. In order to be able to
      offer appropriate and efficient options in every clinical situation, oocyte in
      vitro maturation and ovarian tissue transplantation need to be optimized. Further
      development of new approaches, such as follicular isolation and whole ovary
      transplantation, should be encouraged. Fine ultrastructural details highlighted
      by TEM studies will be useful for the further optimization of these emerging
      technologies.

PMID- 18616903
TI  - A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is
      associated with recurrent miscarriage. Despite the many studies that have
      investigated the prevalence of PCOS in recurrent miscarriage, the extent to which
      PCOS contributes remains highly uncertain. The majority of these studies have
      used the polycystic ovary morphology alone to define PCOS and the results are
      extremely variable due to a variety of diagnostic and selection criteria used.
      Only a very small number of studies have investigated the prevalence of
      hyperandrogenaemia in recurrent miscarriage. Most crucially, to the authors'
      knowledge, there is not yet a single publication which has investigated the true
      prevalence of the complete syndrome of PCOS in recurrent miscarriage using the
      Rotterdam criteria. Hence there is an urgent need to reappraise the prevalence of
      PCOS in recurrent miscarriage using the Rotterdam criteria. The possible
      mechanisms by which PCOS could cause recurrent miscarriage are considered:
      hyperandrogenaemia, obesity and hyperinsulinaemia are the most likely candidates,
      although further work is clearly needed. This paper also reviews the possible
      treatment options for women diagnosed with recurrent miscarriage associated with
      PCOS. There is some evidence to suggest that weight loss, ovarian drilling and
      metformin could help to reduce the rate of miscarriage.

PMID- 18616904
TI  - [Influence of microwave radiation on synapsin I expression in PC12 cells and its
      mechanism].
AB  - AIM: To investigate the effect of microwave radiation on expression and
      phosphorylation of synapsin I and to discover the mechanism by research on the
      change of expression of BDNF and its receptor, TrkB. METHODS: PC12 cells were
      exposed to microwave with average power density being 30 mW/cm(2). HPLC was used
      to detect the release of amino acids; RT-PCR, Western blot and
      immunocytochemistry were used to detect the expressions of synapsin I, BDNF and
      TrkB; immune co-precipitation was used to study the interaction of BDNF and TrkB.
      RESULTS: It resulted in the decrease of the release of Asp, Glu, GABA and Gly at
      1 h (P<0.01) after radiation. Protein of synapsin I was decreased in 9 h-2 d
      (P<0.01 or P<0.05); its mRNA was decreased in 3-9 h and increased at 1 d (P<0.01
      or P<0.05); its phosphorylation was decreased at 3 h, increased at 1 d, and
      decreased at 2 d again (P<0.01 or P<0.05) after radiation. Protein of BDNF was
      decreased at 3 h and increased in 1-2 d (P<0.01 or P<0.05); its mRNA were
      decreased in 3-9 h, increased at 1d, and decreased at 2 d again (P<0.01 or
      P<0.05) after radiation. Protein of TrkB was increased in 3 h-1 d (P<0.01 or
      P<0.05); its mRNA decreased at 3 h and 2 d (P<0.01) after radiation. The
      interaction between BDNF and TrkB was increased in 3-9 h, but decreased in 1-2 d
      (P<0.01 or P<0.05) after radiation. CONCLUSION: Microwave radiation can induce
      the decrease of the release of amino acids and the expression and phosphorylation
      of synapsin I, and the abnormality of expressions and interaction of BDNF and
      TrkB in PC12 cells. The factors might play a role in the injury and repair of
      information transmission in PC12 cells.

PMID- 18616905
TI  - [The role of RKIP mediated ERK pathway in hippocampus neurons injured by
      electromagnetic radiation].
AB  - AIM: To study the effects of electromagnetic radiation on RKIP and phosphorylated
      ERK in primary cultured hippocampus neurons. The inhibitor of MEK U0126 was
      applied to investigate the role of RKIP mediated ERK pathway in radiation injury.
      METHODS: Primary hippocampus neurons were cultured in vitro. X-HPM, S-HPM and EMP
      were taken as radiation source respectively to establish three cell models
      exposed to electromagnetic radiation. RKIP and phosphorylated ERK were measured
      by immunofluorescent labelling and laser scanning confocal microscope. Apoptosis
      and death fraction of the cells were detected by Annexin V-PI double labelling
      and flow cytometry. RESULTS: After three kinds of electromagnetic radiation, the
      expression of RKIP in hippocampus neurons decreased but the expression of
      phosphorylated ERK increased, and its nuclear translocation occurred. No
      significant differences were seen between radiation groups. Apoptosis and death
      fraction of the neurons in U0126 pretreatment groups was significantly lower than
      that in radiation groups but they were still higher than those in sham-radiation
      group. CONCLUSION: The excessive activation of RKIP mediated ERK pathway is one
      of the important mechanisms for the apoptosis and death of hippocampus neurons
      induced by electromagnetic radiation. U0126 have some protective effects on
      radiation injury.

PMID- 18616906
TI  - [Construction of codon-optimized HPV16 capsid genes in the eukaryotic co
      expression vector and transfection of cells].
AB  - AIM: To construct the eukaryotic co-expression vector pcDNA3.1-L1-IRES-L2 for
      harvesting sufficient amounts of infectious HPV16. METHODS: The amplified codon
      optimized HPV16 capsid genes from 988 plasmid by PCR were cloned into pCR-XL-TOPO
      vector and then subcloned into eukaryotic expressing vector pcDNA3.1(+). Thus,
      eukaryotic co-expression vector pcDNA3.1-L1-IRES-L2 capable of expressing HPV L1
      gene and L2 gene was constructed. This eukaryotic vector was verified by
      enzymolysis and sequencing. The transcription of capsid genes was observed in
      vivo and in vitro by hydrodynamics-based transfection and liposome-mediated
      transfection. The expression of L1 gene in 293T cells was examined by Western
      blot. RESULTS: The eukaryotic co-expression vector pcDNA3.1-L1-IRES-L2 was
      successfully constructed and verified by enzymolysis and sequencing.The
      recombinant plasmid L1 and L2 genes were transcripted in the livers of the rats
      and 293T cells.Cytopathic effect (CPE) occurred after the transfected with
      pcDNA3.1-L1-IRES-L2 into 293T cells, indicating that the two capsid genes were
      expressed.Western blot detection showed the recombinant plasmid L1 protein was
      expressed in 293T cells. CONCLUSION: The pcDNA3h1-L1-IRES-L2 has been constructed
      successfully, which lays a foundation for in-dept study on the infectious
      mechanism of HPV16.

PMID- 18616907
TI  - [Promoter methylation regulates KIR3DL1 gene expression in NK-92MI cell line].
AB  - AIM: To investigate the methylation pattern of KIR3DL1 promoter region in NK cell
      line NK-92MI and the effect of demethylation and histone acetylation on gene
      expression, and to study the possible regulation mechanism of KIR3DL1 expression.
      METHODS: The methylation status of KIR3DL1 promoter in NK-92MI cells was detected
      by bisulfite sequencing technique. Then NK-92MI cells were treated with the DNA
      demethylating compound 5-azacytidine and (or) the inhibitor of histone
      deacetylase trichostatin A, and the expression of KIR3DL1 gene was observed.
      RESULTS: The CpG dinucleotides surrounding promoter region of KIR3DL1 gene in NK
      92MI cells were consistently methylated with a frequency of 70%-100%. After 72 h
      treatment with 2.5 micromol/L and 5 micromol/L of 5-azacytidine, the mRNA
      expression of KIR3DL1 gene in NK-92MI cells increased 66.6% and 114.6%,
      respectively. However, after 72 h treatment with 50 nmol/L of trichostatin A, the
      mRNA expression of KIR3DL1 gene in NK-92MI cells did not increase. Additionally,
      combined treatment with 5-azacytidine and trichostatin A did not lead to a
      synergistic effect compared with 5-azacytidine alone. CONCLUSION: KIR3DL1
      expression in NK-92MI cells is regulated by promoter methylation.

PMID- 18616908
TI  - [FK228 promotes the IL-3 mediated proliferation and differentiation of human
      erythroid progenitor cells].
AB  - AIM: To investigate the role of histone deacetylases (HDACs) inhibitor FK228 in
      the IL-3 mediated proliferation and differentiation of human erythroid progenitor
      cells. METHODS: CD34(+) cells were separated from the granulocyte colony
      stimulating factor(G-CSF)-mobilized peripheral blood of cancer patients and
      cultured for 7 days with FK228 of different concentrations, stem cell factor(SCF)
      and interleukin 3 (IL-3) in serum-free medium. Flow cytometry was performed to
      analyze the expression of CD14, GPA, CD15 and CD36 on the cells and the colony
      assay of erythroid cells was conducted. Then the CD36(+)GPA(-) cells were
      enriched and cultured with with IL-3 and 0.5 microg/L FK228 supplemented serum
      free semisolid cultures and the formation test of erythroid colony was conducted.
      RESULTS: FK228 enhanced the generation of CD36(+) cells in a dose-dependent
      manner, in spite of that it displayed no influence on the generation of CD14(+)
      and CD15(+) cells. 0.5 g/L FK228 induced a remarkable increase in the cell number
      of CD36(+) cells cultured with IL-3; FK228 also significantly increased the
      number and size of CD36(+) cells colony cultured with IL-3 containing semisolid
      cultures. Moreover, FK228 augmented the formation of CD36(+) cells colony from
      CD36(+)GPA(-) cells cultured with IL-3. CONCLUSION: FK228 can promote the IL-3
      mediated proliferation and differentiation of human erythroid progenitor cells.

PMID- 18616909
TI  - [Effects of LH analogs on the secretion of NGF in submaxillary gland cells of
      rats in vitro].
AB  - AIM: To investigate the effects of luteinizing hormone (LH) analogs on the
      secretion of nerve growth factor (NGF) in submandibular gland cells of rats in
      vitro. METHODS: The submandibular gland cells of rats were incubated in vitro and
      LH analogs at various concentration were added to the medium. The never growth
      factor (NGF) was detected by enzyme-link immunoassay (ELISA). RESULTS: When LH
      analogs were at the concentration of 10(-6), 10(-4), 10(-2) U/L respectively, the
      secretion of NGF was gradually increased. However, when LH analogs were at the
      concentration of 10(-2), 10(0), 10(2) U/L respectively, the secretion of NGF was
      gradually decreased. When LH analogs (10(-5) IU/mL) were incubated at different
      time, the secretion of NGF was different. NGF reached the peak value when it was
      incubated for 8 h and then decreased gradually. CONCLUSION: LH analogs may
      regulate the secretion of NGF in the submaxillary gland cells of rats.

PMID- 18616910
TI  - [Establishment of B16-HLA-MAGE-3 melanoma cell line coexpressing HLA-A 0201/K(b)
      and MAGE-3 and its role in tumor vaccine evaluation].
AB  - AIM: To establish a tumor model in HLA-A2.1 transgenic mice to examine the
      efficacy of MAGE-3 vaccine, a cell line coexpressing HLA-A 0201/K(b) and MAGE-3
      is established. METHODS: B16-HLA-MAGE-3 melanoma was obtained by means of
      cotransfection of HLA-A 0201/K(b) and MAGE-3 to B16 melanoma. RT-PCR, FCM
      analysis and Western blot were used to detect the mRNA or protein of HLA-A
      0201/K(b) or MAGE-3 expression in B16-HLA-MAGE-3. The ability of MAGE-3 antigen
      to be processed and presented in the B16-HLA-MAGE-3 cell line were observed by
      CTL activity detection and tumor challenge test. RESULTS: Transcription and
      protein expression of HLA-A 0201/H-2k(b) and MAGE-3 were demonstrated in B16-HLA
      MAGE-3 cells. CTL activity of splenocytes in immunized mice against B16-HLA-MAGE
      3 was detected and the growth of B16-HLA-MAGE-3 in immunized mice was also
      inhibited. CONCLUSION: MAGE-3 antigen is able to be processed and presented
      efficiently by B16-HLA-MAGE-3 melanoma cells and this cell can be employed to
      test HLA-A2 restricted epitope immunogenicity in the A2-transgenic mice.

PMID- 18616911
TI  - [Effect of yupingfengsan on the growth of tumor and immunological function in
      tumor-bearing mice].
AB  - AIM: To explore the effect of yupingfengsan on the growth of tumor and
      immunological function in tumor-bearing mice. METHODS: The models of tumor
      bearing mice were established by inoculating the healthy mice with S180 tumor
      carneus cells cultured in vitro. Then the ratio of tumor restriction was
      calculated. The phagocytosis activity of phagocytes, the level of NO secreted by
      phagocytes, the proliferating activity of T lymphocytes and the level of IL-2
      were detected in the mice after being treated with yupingfengsan 12 days.
      RESULTS: yupingfengsan elevated the phagocytosis of phagocytes and the level of
      NO secreted by phagocytes. It promoted T lymphocytes to transform, and increased
      the level of IL-2 and the activity of NK cells. CONCLUSION: yupingfengsan can
      increase the immunological function of tumor-bearing mice and suppress the
      development of tumor in mice.

PMID- 18616912
TI  - [Immune response induced by Rpf domain from Micrococcus luteus in mice].
AB  - AIM: To investigate the immunobiology of Rpf domain from Micrococcus luteus.
      METHODS: BALB/c mice were immunized with Rpf domain three times at 2-week
      interval. ELISA was used to detect the title of the anti-Rpf domain antibody
      titer in the immunized mice sera. The spleen lymphocytes of the immunized mice
      were separated and the stimulation index (SI) was measured by MTT colorimetry.
      The levels of secreted IFN-gamma, IL-10 and IL-12 upon specific antigen
      stimulation was detected by ELISA. The Rpf domain immunized BALB/c mice were
      intravenously infected with 10(5) CFU MTB H37Rv. The number of CFU in the spleens
      was determined four weeks after final injection. RESULTS: The titer of the
      specific antibody in sera of the immunized BALB/c mice was 1:128 000. The SI of
      Rpf domain immunized group (2.10+/-0.12) was significantly higher than that of
      saline immunized group (0.90+/-0.21). The lever of IFN-gamma, IL-10 and IL-12
      levels in culture supernatant of spleen lymphocytes from the fusion protein
      immunized mice was (1 126+/-36) ng/L, (368+/-13) ng/L and (289+/-14) ng/L,
      respectively, which was markedly higher than that of saline immunized group
      (P<0.01). Compared with normal saline immunized mice (6.64+/-0.13) four weeks
      after final injection, dramatic reduction in MTB replication was observed in the
      spleen (5.03+/-0.11) from the BALB/c mice immunized with fusion proteins.
      CONCLUSION: Rpf domain can be used as a candidate for a new TB vaccine.

PMID- 18616913
TI  - [Construction of multi-epitope DNA vaccine for Toxoplasma gondii and the study on
      protective immunity response in mice].
AB  - AIM: To construct multi-epitope DNA vaccine for Toxoplasma gondii and study its
      protective immunity response. METHODS: The gene encoding six polypeptides of T.
      gondii, which consists of plenty of T and B epitopes, was cloned into the
      eucaryotic expression vector pcDNA3.1(+). BALB/c mice were vaccinated by this
      multi-epitope based DNA vaccine (intramuscular needle injection). The specific
      antibody and T cell proliferation were determined. Meanwhile, the DNA-vaccinated
      mice were challenged with a lethal dose of T. gondii tachyzoites for further
      observation. RESULTS: The eukaryotic expression plasmid (pcDNA3.1/T-ME) encoding
      plenty of T. gondii epitopes was constructed successfully. pcDNA3.1/T-ME
      immunization induced T. gondii specific humoral and cellular immunity in mice.
      The mice immunized with pcDNA3.1/T-ME survived significantly longer than the mice
      in control after challenged by T. gondii RH strain infection. CONCLUSION: The
      multi-epitope DNA vaccine can induce the protective immunity against T. gondii
      infection effectively in vivo, which is a potential strategy to control T. gondii
      infection.

PMID- 18616914
TI  - [The effects of Lysophospholipase from Clonorchis sinensis on the hepatic
      stellate cells and oval cells of rat].
AB  - AIM: To clarify the effects of the recombinant protein of Lysophospholipase from
      Clonorchis sinensis (CsLysoPLA) on the hepatic stellate cells (HSC) and oval
      cells of rat. METHODS: Binding of the recombinant CslysoPLA protein to the
      membrane of HSC and oval cells was identified by immunofluorescent staining. The
      HSC and oval cells were cultured and treated with the recombinant protein at
      different doses, and proliferation was quantified by MTT method. Cell cycle
      analysis was performed by flow cytometry. RESULTS: The recombinant CslysoPLA
      protein could bind to the membrane of HSC and oval cells. Compared to control, 2
      mg/L and 20 mg/L the recombinant protein could promote HSC and oval cells growth
      (P<0.05), whereas 200 mg/L the recombinant protein could induce the cells
      necrosis, which associated with overt plasma membrane disruption. Oval cell
      number in G(2) phase of the recombinant protein 20 mg/L treated group was higher
      than that of control group. CONCLUSION: In vitro, the recombinant protein could
      induce HSC and oval cells proliferation at low concentrations (2 mg/L and 20
      mg/L), whereas it also could induce the cells necrosis at high concentration (200
      mg/L). These results suggested that CslysoPLA might play a role in the
      pathogenicity of C. sinensis.

PMID- 18616915
TI  - [Preparation and preliminary application of rabbit anti-human PON2
      antibodies(paraoxonase-2)].
AB  - AIM: To preparation and characterize the rabbit polyclonal antibodies against
      human PON2 (paraoxonase-2). METHODS: A fragment of human PON2 gene which was of
      low homology with rabbits but of higher hydrophilicity and immunogenicity was
      selected for recombinant expression in prokaryotic expression system. The rabbits
      were immunized with the purified GST fusion protein 3 times. The specificity and
      sensitivity of the anti-human PON2 polyclonal antibodies were detected by Western
      blot and indirect immunofluorescence. RESULTS: The GST-PON2 fusion protein was
      highly expressed in Ecoli with a molecular weight of 46 kDa. Western blot
      analysis proved the rabbit polyclonal antibodies could specifically recognize 39
      kDa native PON2 protein expressed in several cells and tissues, such as HeLa
      cells, U937 cells, and human liver tissue. Indirect immunofluorescence analysis
      confirmed that PON2 protein was located in the cytoplasm of SY5Y cells.
      CONCLUSION: The rabbit polyclonal antibodies against human PON2 can specifically
      recognize natural protein expressed in human cells and tissues, Which can be used
      for further study and clinical detection of human PON2.

PMID- 18616916
TI  - [Preparation of hen egg yolk immunoglobulin and partial plasma high abundant
      protein depletion by prepared chicken immunoglobulin coupled on GoldMag carrier].
AB  - AIM: To prepare specific egg yolk immunoglobulin (IgY) against HSA and IgG and to
      make HSA and IgG depletion research in human plasma by binding it to the surface
      of GoldMag. METHODS: Laying Roman hens immunized with different antigens, such as
      HSA, IgG and the mixtures of these proteins were used in the experiments. The
      best condition of isolating the IgY antibody was studied. The titer and purity of
      the antibody were examined by indirect ELISA and SDS-PAGE respectively. Then the
      specific IgY was bound to the surface of GoldMag for HSA and IgG depletion
      research. RESULTS: 60-120 days after immunization, the titer of the antibody in
      the plasma against different antigens reached 1:15 000-1:25 000; while the titer
      in the egg reached 1:10 000-1:25 000. The purity was over 98%. Most of HSA and
      IgG were depleted from human plasma by IgY connected to GoldMag. CONCLUSION: HSA
      and IgG can be used as antigens to immunize laying hens to produce IgY with high
      titer and purity. IgY which is bound to the GoldMag carrier can be used to
      deplete of the relevant HSA and IgG from human plasma effectively. As a new
      method of studying proteome of plasma, it has some practical applications.

PMID- 18616917
TI  - [Prokaryotic expression, purification and preparation of polyclonal antibody for
      human SUMO-2 gene].
AB  - AIM: To construct a prokaryotic expression vector of human SUMO-2, purify GST
      SUMO2-SUMO2 fusion protein produced by the expression system, and prepare its
      antiserum. METHODS: The human SUMO-2 gene was amplified by PCR. The target
      fragment digested by the enzyme was cloned into a pET41a(+) expression vector and
      then transfected into E.coli. BL21 (DE3) pLysS, in which GST-SUMO2-SUMO2 fusion
      protein was induced by IPTG. After the soluble protein was purified by GST
      affinity chromatography and by identified by SDS-PAGE, the rabbits were immunized
      with the fusion protein and the antiserum was obtained. RESULTS: DNA sequence
      analysis showed the cloned SUMO-2 gene sequence was completely corresponding to
      GenBank data. SDS-PAGE and Western blot showed that the GST-SUMO2-SUMO2 fusion
      protein was about 52 kDa, which was mainly the soluble protein of E.coli and
      could be purified by GST affinity chromatography. The result of ELISA was
      positive and Western blot confirmed the antiserum reacted specifically to SUMO-2
      protein. CONCLUSION: SUMO-2 protein and its specific polyclonal antibody have
      been prepared, which provides a basis for the establishment of immunoassays of
      human SUMO-2.

PMID- 18616918
TI  - [Preparation and distribution of polyclonal antibodies against human PIWIL3
      protein in tumor tissues].
AB  - AIM: To prepare specific antibodies against human PIWIL3 protein of Argonaute
      family and study its expression and distribution in human tumors. METHODS: To
      synthesize the polypeptide using the optimal polypeptide immunogens based on
      sequence homology and peptide immunogenicty in the internal polypeptide selecting
      database. The synthesized polypeptide were combined with KLH, then immunized the
      experimental rabbits to produce antiserum. The antiserum was purified by gels
      custodited the polypeptide using affinity chromatograph, and validated its
      ability to combine with the corresponding proteins by enzyme-linked
      immunosorbentassay (ELISA) and Western blot. The expression and distribution of
      PIWIL3 protein were detected by human tumor tissue biochips. RESULTS: The
      specific antibodies against human PIWIL3 proteins were prepared and had high
      purity. PIWIL3 proteins were expressed in the cytoplasma of human astrocytic
      glioma and meningioma. CONCLUSION: The specific antibodies against human PIWIL3
      protein have been successfully prepared by using the internal polypeptide
      selecting database to obtain the optimal polypeptide immunogens, which are
      distinguished from other sequence homology proteins in the subfamily. These
      antibodies will have potential value for human PIWIL3 protein in human specific
      tumor pathogenesis.

PMID- 18616919
TI  - [Effects of activated PPARgamma on the expression of PTEN gene in pancreatic
      cancer cells].
AB  - AIM: To explore the relationship between the expression of PTEN gene and the
      expression of PPARgamma, and the human pancreatic cancer cells PANC-1 were
      cultured in vitro. METHODS: The effects of rosiglitazone and GW9662 on the
      expression of PTEN gene and PTEN protein in the human pancreatic cancer cells
      PANC-1 were detected by RT-PCR and immunohistochemistry respectively. In
      addition, the percentage of the expression of PTEN protein was analyzed by flow
      cytometry. RESULTS: The expression of PTEN gene and PTEN protein in human
      pancreatic cancer cells PANC-1 were all increased significantly after treated
      with rosiglitazone. While those were markedly reduced in GW9662 treated groups,
      and it has a dose-effect relationship between them. CONCLUSION: The expression of
      PTEN gene were paralleled with the expression of PPARgammain human pancreatic
      cancer cells PANC-1, which may be related to its inhibitory effects on pancreatic
      tumor cells.

PMID- 18616920
TI  - [Circulating levels of oxidative stress and adipocytokines in obese subjects].
AB  - AIM: To investigate the relationship between adipocytokines levels and oxidative
      stress in obese males. METHODS: The levels of 8-iso-prostaglandinF2alpha(8-iso
      PGF2alpha), superoxide dismutase (SOD), malondialdehyde (MDA), adiponectin,
      leptin, restistin, TNF-receptors 1(TNF-R1), Interleukin-1beta(IL-1beta) and
      Interleukin-6(IL-6) were measured in obese men and normal controls. RESULTS: The
      levels of 8-iso-PGF(2alpha), MDA, leptin, TNF-R1, IL-1beta and IL-6 was
      significantly higher than that normal controls (P<0.05, P<0.01). The levels of
      adiponectin and the activity of SOD decreased significantly in obese men.There
      was no significant difference in the restistin between obese men and normal
      controls. There was significantly positive correlation between 8-iso-PGF(2alpha)
      and body mass index (BMI) (r=0.54, P<0.05) in obese. A significantly negative
      correlation was found between 8-iso-PGF(2alpha) and adiponectin (r=-0.56, P<0.05)
      in obese subjects. The levels of leptin was negative correlated with body fat
      content(%)(r=-0.53, P<0.05) in obese subjects. A significant negative correlation
      was observed between the levels of adiponectin and LDL(r=-0.54, P<0.05), IL-6 (r=
      0.41, P<0.05). In a multiple regression analysis model, the levels of adiponectin
      and IL-6 were the main determinants of the oxidative stress in obese men.
      CONCLUSION: Changed concentration of adipocytokines was found in obese men. There
      are significantly correlation with between oxidative stress and adipocytokines.

PMID- 18616921
TI  - Presence of insensitive acetylcholinesterase in wild populations of Culex pipiens
      quinquefasciatus from Benin.
AB  - Resistance to organophosphates and carbamates was investigated in three samples
      of Culex pipiens quinquefasciatus Say, from Cotonou and Parakou in the Republic
      of Benin. Each population of larvae was selected with propoxur to eliminate
      susceptible individuals and more easily analyse resistant mosquitoes if the
      resistance allele is present in the field sample. The mass-selection showed that
      there are resistant mosquitoes in natural populations of C. p. quinquefasciatus
      in Benin and that nowadays they are still at a low frequency. The result of the
      PCR-based assay revealed the presence of the G119S mutation in all the C. p.
      quinquefasciatus mosquitoes that survived exposure to mass-selection. This
      mutation is the same than reported in a large range of insects, including
      Anopheles gambiae. Thus, the G119S mutation is spreading in natural populations
      of C. p. quinquefasciatus in Africa. Therefore, good mosquito control strategies
      and agricultural use of insecticides are critical, and should be carefully
      applied to limit the spread of this resistance gene.

PMID- 18616922
TI  - Determination of serum methylmalonic acid by alkylative extraction and liquid
      chromatography coupled to tandem mass spectrometry.
AB  - Despite the new advances in bioanalytical techniques, the analysis of low
      molecular-weight organic acids in complex matrices is still a challenge. Although
      new strategies applying liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      seem to be promising, sample preparation methodologies hamper its application in
      most clinical laboratories. The quantitation of methylmalonic acid (MMA) in
      biological matrices is an emblematic example due to its low concentration, the
      need for derivatization to increase its molecular weight, and the presence of the
      physiologically more abundant isomer succinic acid. Here we present a new
      strategy for rapid and sensitive MMA quantitation by combining alkylative
      extraction and LC-MS/MS. Alkylative extraction conditions were optimized to allow
      endogenous detection of MMA using only 50 microL of serum with a short sample
      preparation procedure. The formation of a unique ion from the MMA
      dipentafluorobenzyl derivative in negative atmospheric pressure chemical
      ionization (APCI) allowed its detection with high sensitivity and with no
      interference from succinic acid, a more abundant physiologically present isomer.

PMID- 18616924
TI  - Ten-minute purification of PCR products by continuous elution electrophoresis.
AB  - We optimized continuous elution electrophoresis (CEE) for rapid purification of
      PCR products. After PCR amplification, the reaction mixture is applied directly
      to CEE, and then the PCR products in the size range from 200 to 1500 bp are
      purified within nearly 10 min. CEE is able to separate two DNA fragments
      differing in length by 50 bp. As judged by ligation efficiency, the quality of
      PCR products separated by CEE is equal to that purified by extraction from the
      melting gels. CEE reduces operational time because purification of the PCR
      products is a repetitional procedure in recombinant DNA techniques.

PMID- 18616923
TI  - An Escherichia coli expression system for glutamyl endopeptidases optimized by
      complete suppression of autodegradation.
AB  - V8 protease (GluV8), a member of the glutamyl endopeptidase I family isolated
      from the V8 strain of Staphylococcus aureus, is widely used for proteome analysis
      because of its unique substrate specificity and resistance to detergents. We
      recently developed an Escherichia coli expression system for the production of
      GluV8 based on a technique that suppresses the autoproteolysis--the use of the
      prosequence of its homologue (GluSE) from Staphylococcus epidermidis as a
      chimeric form or the introduction of four substitutions in the prosequence of
      GluV8. In the current study, we refined this technique through five amino acid
      substitutions within the prosequence of GluV8 for complete suppression of the
      autodegradation. As a result, the recovery of GluV8 proform was enhanced to 20
      fg/cell, which was comparable to the level of a constitutive inactive form of
      GluV8, indicating complete suppression of the autoproteolysis. This mutated
      propeptide was also effective for the expression of the mature sequence of the
      glutamyl endopeptidase from Staphylococcus warneri. The recombinant proteins were
      successfully converted to their active forms through a common cleavage mechanism
      mediated by thermolysin in vitro. This strategy may shed light on the way for the
      expression of the proteases that have been scarcely produced in E. coli to date.

PMID- 18616925
TI  - Enzyme microarrays assembled by acoustic dispensing technology.
AB  - Miniaturizing bioassays to the nanoliter scale for high-throughput screening
      reduces the consumption of reagents that are expensive or difficult to handle.
      Through the use of acoustic dispensing technology, nanodroplets containing 10
      microM ATP (3 microCi/microL (32)P) and reaction buffer in 10% glycerol were
      positionally dispensed to the surface of glass slides to form 40-nL compartments
      (100 droplets/slide) for Pim1 (proviral integration site 1) kinase reactions. The
      reactions were activated by dispensing 4 nL of various levels of a
      pyridocarbazolo-cyclopentadienyl ruthenium complex Pim1 inhibitor, followed by
      dispensing 4 nL of a Pim1 kinase and peptide substrate solution to achieve final
      concentrations of 150 nM enzyme and 10 microM substrate. The microarray was
      incubated at 30 degrees C (97% R(h)) for 1.5 h. The spots were then blotted to
      phosphocellulose membranes to capture phosphorylated substrate. With phosphor
      imaging to quantify the washed membranes, the assay showed that, for doses of
      inhibitor from 0.75 to 3 microM, Pim1 was increasingly inhibited. Signal-to
      background ratios were as high as 165, and average coefficients of variation for
      the assay were approximately 20%. Coefficients of variation for dispensing
      typical working buffers were under 5%. Thus, microarrays assembled by acoustic
      dispensing are promising as cost-effective tools that can be used in protein
      assay development.

PMID- 18616926
TI  - Identification of preferred substrate sequences of microbial transglutaminase
      from Streptomyces mobaraensis using a phage-displayed peptide library.
AB  - Microbial transglutaminase (TGase) from Streptomyces mobaraensis (MTG) has been
      used in many industrial applications because it effectively catalyzes the
      formation of covalent cross-linking between glutamine residues in various
      substrate proteins and lysine residues or primary amines. To better understand
      the sequence preference around the reactive glutamine residue by this enzymatic
      reaction, we screened preferred peptide sequences using a phage-displayed random
      peptide library. Most of the peptides identified contained a consensus sequence,
      which was different from those previously found for mammalian TGases. Of these,
      most sequences had a specific reactivity toward MTG when produced as a fusion
      protein with glutathione-S-transferase. Furthermore, the representative sequence
      was found to be reactive even in the peptide form. The amino acid residues in the
      sequence critical for the reactivity were further analyzed, and the possible
      interaction with the enzyme has been discussed in this paper.

PMID- 18616927
TI  - Comparison of the interaction of tomatine with mixed monolayers containing
      phospholipid, egg sphingomyelin, and sterols.
AB  - The interaction of the glycoalkaloid tomatine with monolayers of a phospholipid
      (dimyristoylphosphatidylcholine, DMPC), and sphingolipid (egg sphingomyelin), and
      cholesterol is compared. Using measurements of the surface pressure response as a
      function of the subphase concentration of tomatine, interfacial binding constants
      are estimated for mixed monolayers of DMPC and cholesterol and for those of egg
      sphingomyelin and cholesterol of mole ratio 7:3. The binding constants obtained
      suggest a stronger interaction of tomatine with DMPC and cholesterol mixed
      monolayers, reflecting easier displacement of cholesterol from its interaction
      with DMPC than from its interaction with egg sphingomyelin. Mixtures of tomatine
      and cholesterol are found to spread directly at the water-air interface and form
      stable monolayers, suggesting that cholesterol holds tomatine at the interface
      despite the absence of observed monolayer behavior for tomatine alone. The
      interaction of tomatine with DMPC and cholesterol monolayers is found to exhibit
      a pH dependence in agreement with previously reported results for its interaction
      with liposomes; in particular, the interaction is much less at pH 5 than at pH 7
      or pH 9. It is found that while tomatine interacts strongly with monolayers
      containing sitosterol, it does not interact with monolayers containing sitosterol
      glucoside. The response of monolayers of varying composition of DMPC and
      cholesterol to tomatine is also examined. Brewster angle microscopy (BAM) reveals
      further evidence for formation of suspected islands of tomatine + cholesterol
      complexes upon interaction with mixed monolayers of lipid and sterol.

PMID- 18616928
TI  - Essential role of Chk1 in S phase progression through regulation of RNR2
      expression.
AB  - Chk1 is an essential kinase for maintaining genome integrity and cell cycle
      checkpoints through phosphorylating several downstream targets. Recently, we
      demonstrated that Chk1 is also required for cell proliferation in somatic cells
      under unperturbed condition through regulating transcription of several genes.
      Here, we show that Chk1 is required for S phase progression and RNR2 is a
      critical downstream target of genes transcriptionally regulated by Chk1. Hence,
      although RNR2 expression reached maximum at S phase in the presence of Chk1, Chk1
      depletion arrested the cell cycle at S phase and reduced RNR2 expression at both
      mRNA and protein levels. Ectopic expression of RNR2 failed to rescue the S phase
      arrest observed in Chk1 depleted cells, suggesting the presence of an additional
      Chk1-target(s) for completion of S phase other than RNR2. Therefore, our results
      suggest that Chk1 is required for DNA replication at least through regulating
      RNR2 gene transcription.

PMID- 18616929
TI  - Proteomic analysis uncovers a metabolic phenotype in C. elegans after nhr-40
      reduction of function.
AB  - Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding
      nuclear hormone receptors, most of which are nematode-specific and are of unknown
      function. We have exploited comparative two-dimensional chromatography of
      synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to
      determine if proteomic approaches will provide additional insight into gene
      function. Chromatofocusing, followed by reversed-phase chromatography and mass
      spectrometry, identified altered chromatographic patterns for a set of proteins,
      many of which function in muscle and metabolism. Prompted by the proteomic
      analysis, we find that the penetrance of the developmental phenotypes in the
      mutant is enhanced at low temperatures and by food restriction. The combination
      of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a
      link between metabolism and muscle development. Our results highlight the utility
      of comparative two-dimensional chromatography to provide a relatively rapid
      method to gain insight into gene function.

PMID- 18616930
TI  - Lysophosphatidylserine stimulates chemotactic migration in U87 human glioma
      cells.
AB  - Lysophosphatidylserine (LPS) was found to stimulate intracellular calcium
      increase in U87 human glioma cells. LPS also stimulated chemotactic migration of
      U87 human glioma cells, which was completely inhibited by pertussis toxin (PTX).
      Moreover, LPS was also found to stimulate ERK, p38 MAPK, JNK, and Akt activities
      in U87 cells. We observed that LPS-induced U87 chemotaxis was mediated by PI3K,
      p38 MAPK, and JNK. LPS-induced chemotactic migration in U87 cells was inhibited
      by Ki16425, an LPA(1/3) receptor-selective antagonist, which suggested that the
      Ki16425-sensitive G-protein coupled receptor (GPCR) played a role in this
      process. Moreover, U87 cells were found to uniquely express LPA(1) but not LPA(2
      5). In addition, LPS failed to stimulate the NF-kappaB-driven luciferase activity
      in exogenously LPA(1)-transfected HepG2 cells. Taken together, we propose that
      LPS stimulates GPCR, which is in contrast to the well-known LPA receptors, thus
      resulting in the chemotactic migration in U87 human glioma cells.

PMID- 18616931
TI  - Blocking CD147 induces cell death in cancer cells through impairment of
      glycolytic energy metabolism.
AB  - CD147 is a multifunctional transmembrane protein and promotes cancer progression.
      We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly
      induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer
      cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts.
      Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM
      M6/1 induced cell death, respectively. CD147 is known to form complex with proton
      linked monocarboxylate transporters (MCTs), which is critical for lactate
      transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1
      co-localized on the cell surface, and MEM-M6/1 inhibited the association of these
      molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi.
      Further, the induction of acidification was parallel to the decrease of the
      glycolytic flux and intracellular ATP levels. These effects were not found in the
      normal fibroblasts. As cancer cells depend on glycolysis for their energy
      production, CD147 inhibition might induce cell death specific to cancer cells.

PMID- 18616932
TI  - Inhibition of matrix metalloproteinase-9 attenuated neural progenitor cell
      migration after photothrombotic ischemia.
AB  - Recent studies have shown that neuroblasts migrate from the subventricular zone
      (SVZ) into the injured area after ischemic brain insults. However, it is not well
      understood which mechanism mediates this ectopic migration and which types of
      cells migrate into the damaged region from the SVZ. The present study was
      designed to investigate the characteristics of the migration of nestin-positive
      neural stem cells toward the region of ischemic injury after focal cortical
      ischemia. Nestin-eGFP transgenic mice were used to effectively model the
      migration of SVZ cells. Photothrombotic ischemia was induced by injection of rose
      bengal (30 mg/kg) and exposure to cold light. Migration of nestin-positive cells
      was examined using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate (DiI) and bromodeoxyuridine (BrdU) labeling. The number of nestin
      positive cells was increased significantly in the peri-infarct area at 5 and 7
      days after photothrombosis. A subset of nestin-positive cells was co-labeled with
      DiI or BrdU. Some of the nestin-positive cells co-expressed doublecortin (DCX)
      and only a few nestin-positive cells co-labeled with anti-epidermal growth factor
      receptor (EGFr) antibody. However, no nestin-positive cells were immunoreactive
      for glial fibrillary acidic protein (GFAP). The inhibition of matrix
      metalloproteinases (MMPs) using the MMP inhibitor, FN-439, decreased nestin
      positive cells in the peri-infarct region at 7 days after photothrombosis.
      Although MMP-9 was not co-expressed in the nestin-positive cells in the peri
      infarct cortex, MMP-9 did co-localize with GFAP-positive astrocytes. These
      results suggest that nestin-positive neural progenitor cells migrate into the
      peri-infarct cortex after photothrombotic ischemia and that MMP-9 is involved in
      the migration.

PMID- 18616933
TI  - Age-dependent decline in hippocampal neurogenesis is not altered by chronic
      treatment with fluoxetine.
AB  - There has been ongoing controversy as to whether selective serotonin reuptake
      inhibitors (SSRIs) exhibit the same antidepressant efficacy and risk profile
      within different age groups. Although the etiology of such potential differences
      is currently not clear, age-dependent differences in the rate of hippocampal
      neurogenesis offer one possibility. In the current studies we have therefore
      examined whether fluoxetine, the prototypical selective serotonin reuptake
      inhibitor, differentially modulates neurogenesis in adolescent, young adult, and
      aged rats. Proliferation in the dentate gyrus was measured by assaying expression
      of the endogenous proliferative marker, Ki67. Survival of proliferating cells was
      assayed by staining with BrdU. We confirmed previous reports that the rate of
      neurogenesis, as well as the survival of proliferating cells, decreases
      significantly with age. Moderate decreases were found in young adult rats
      relative to adolescent rats, and profound decreases were found in aged rats. We
      additionally found that age did not alter the response to 25 days of treatment
      with fluoxetine. In fact, we did not observe enhancement of hippocampal
      neurogenesis, nor enhancement of proliferating cell survival, in any of the three
      age groups despite using doses of fluoxetine which have been reported to be
      effective. In addition to finding no age-dependent effects, our data question the
      general reproducibility of previously reported fluoxetine effects in animals.

PMID- 18616934
TI  - Theta oscillations during the processing of monetary loss and gain: a perspective
      on gender and impulsivity.
AB  - Event-related oscillations (EROs) have proved to be very useful in the
      understanding of a variety of neurocognitive processes including reward/outcome
      processing. In the present study, theta power (4.0-7.0 Hz) following outcome
      stimuli in the time window of the N2-P3 complex (200-500 ms) was analyzed in
      healthy normals (20 males and 20 females) while performing a gambling task that
      involved monetary loss and gain. The main aim was to analyze outcome processing
      in terms of event-related theta power in the context of valence, amount, gender,
      and impulsivity. The S-transform was used for the signal processing of the ERO
      data in terms of time-frequency-power. Results from filtered waveforms showed a
      partially consistent phase-alignment of the increased theta activity
      corresponding to N2 and P3 components following the outcome stimuli. Gain
      conditions produced more theta power than loss conditions. While there was
      anterior involvement in both gain and loss, posterior activation was stronger
      during gain conditions than during loss conditions. Females exhibited posterior
      maxima during gain conditions while males had an anterior maxima during both loss
      and gain conditions. The current source density of theta activity in females
      involved larger areas with a bilateral frontal activity while males predominantly
      had a frontal midline activity. Theta power was significantly higher in females
      than males across all conditions. Low theta (4.0-5.5 Hz) predominantly
      contributed to the posterior activity during gain conditions. High theta (5.5-7.0
      Hz) was more associated with impulsivity measures than low theta activity. These
      findings may offer valuable clues to understand outcome processing, impulsivity,
      and gender differences.

PMID- 18616935
TI  - Value of serum anti-p53 antibodies as a prognostic factor in Egyptian patients
      with hepatocellular carcinoma.
AB  - OBJECTIVE: p53 antigen is an oncoprotective antigen and when damaged, leads to
      production of anti-p53 and also predisposes to various cancers, including
      hepatocellular carcinoma (HCC). Serum anti-p53 has been proven to have a
      prognostic value in patients with HCC. The objective of this study was to
      determine the prevalence and prognostic utility of serum anti-p53 in Egyptian
      patients with HCC. METHODS: Forty one patients with HCC, 26 patients with liver
      cirrhosis and 29 healthy controls were included in this study. For all the
      studied groups, we studied the clinical data, abdominal ultrasound (US) findings,
      biochemical liver function tests, serum alpha-fetoprotein (AFP) levels detected
      by enzyme immunoassay (EIA) kit and anti-p53 antibody levels by a modified enzyme
      linked immunosorbent assay (ELISA). The severity of liver disease was assessed by
      Child-Pugh and MELD scores. Tumor characteristics were detected by (US) with or
      without computed tomography (CT) scan. These characteristics included tumor size,
      number and site. Tumor staging was done using Okuda, Cancer Liver Italian Program
      (CLIP) and Tokyo staging systems. Also, the overall survival of patients with HCC
      with reference to p53 antibody level was studied. RESULTS: The mean age of HCC
      patients was 57.95+/-8.41. There was a male predominance among HCC patients with
      male-to-female ratio of 3.6:1. Anti-p53 antibodies were detected in the sera of
      68.3% of HCC patients, 50% of liver cirrhosis patients and 17.2% of healthy
      control subjects. The data showed that HCC patients had a significantly higher
      mean anti-p53 antibody values (p=0.0001), than both liver cirrhosis patients and
      healthy control groups. Our results revealed that anti-p53 has a positive
      significant correlation with AFP (p=0.002), severity of liver disease [Child Pugh
      score (p=0.02) and MELD score (p=0.0003)], tumor size (p<0.0001), tumor number
      (p=0.003) and tumor staging systems [Okuda (p=0.04), CLIP (p=0.006) and Tokyo
      (p<0.0001)]. Also, our results revealed that serum anti-p53 antibodies had a
      significant association with overall survival of patients with HCC (p=0.019) with
      a shorter survival time in anti-p53 positive status patients and with higher anti
      p53 antibody levels within 19 months follow up. CONCLUSION: The detection of anti
      p53 antibodies may be suitable for assessing the prognosis of HCC patients. The
      higher percentage of positivity of anti-p53 antibodies in Egyptian control
      subjects than reported elsewhere needs further thorough investigation.

PMID- 18616936
TI  - DNA methyltransferase loading, but not de novo methylation, is an oocyte
      autonomous process stimulated by SCF signalling.
AB  - Epigenetic reprogramming occurs during oocyte growth in mice, a stage where a
      number of important events are occurring, including transcription of maternal
      mRNAs for storage in the mature egg, global transcriptional silencing and the
      acquisition of meiotic competence. Oocyte growth occurs in conjunction with
      follicular development over a period of many days. The signals involved in
      initiating different stages in oocyte and follicular development and the
      concurrent epigenetic changes are poorly understood. Here we examine the role of
      stem cell factor (SCF or Kit ligand) on the early- to mid-stages of oocyte growth
      and on DNA methyltransferase expression and function using a one-step in vitro
      culture system. Our results show that SCF promotes early oocyte growth and
      development to the multilaminar follicle stage. Oocyte growth is sufficient to
      trigger transcription of Dnmt1 and Dnmt3L from dedicated oocyte promoters, and we
      show that eggs undergoing growth in the absence of follicle development in Foxo3
      mutants show elevated levels of Dnmt1. The methyltransferase proteins undergo
      sequential relocalisation in the oocyte, with DNMT1 being exported from the
      nucleus at the bilaminar follicle stage, while DNMT3A is transported into the
      nucleus at the multilaminar stage, indicating an important role for trafficking
      in controlling imprinting. SCF is thought to signal partly through the
      phophostidylinositol 3 (PI3) kinase pathway: inhibiting this path was previously
      shown to prevent FOXO3 nuclear export and we could show here that it also
      prevented DNMT1 export. Some oocytes reached full size (70 microM) in this in
      vitro system, but no secondary follicles were formed, most likely due to failure
      of the thecal layer to form properly. De novo methylation of imprinted genes was
      seen in some oocyte cultures, with methylation levels being highest for Snrpn and
      Igf2r which are methylated early in vivo, while Peg1, which is methylated late,
      showed little or no methylation. SCF treatment did not increase the number of
      cultures showing methylation. We saw no evidence for de novo methylation of IAP
      repeats in our cultures. These results suggest that while methyltransferase
      loading is triggered by oocyte growth, in which SCF plays an important role,
      complete methylation probably requires progression to the secondary follicle
      stage and is unlikely to be affected by SCF.

PMID- 18616937
TI  - Founder cells regulate fiber number but not fiber formation during adult
      myogenesis in Drosophila.
AB  - During insect myogenesis, myoblasts are organized into a pre-pattern by
      specialized organizer cells. In the Drosophila embryo, these cells have been
      termed founder cells and play important roles in specifying muscle identity and
      in serving as targets for myoblast fusion. A group of adult muscles, the dorsal
      longitudinal (flight) muscles, DLMs, is patterned by persistent larval scaffolds;
      the second set, the dorso-ventral muscles, DVMs is patterned by mono-nucleate
      founder cells (FCs) that are much larger than the surrounding myoblasts. Both
      types of organizer cells express Dumbfounded, which is known to regulate fusion
      during embryonic myogenesis. The role of DVM founder cells as well as the DLM
      scaffolds was tested in genetic ablation studies using the UAS/Gal4 system of
      targeted transgene expression. In both cases, removal of organizer cells prior to
      fusion, causes formation of supernumerary fibers, suggesting that cells in the
      myoblast pool have the capacity to initiate fiber formation, which is normally
      inhibited by the organizers. In addition to the large DVM FCs, some (smaller)
      cells in the myoblast pool also express Dumbfounded. We propose that these cells
      are responsible for seeding supernumerary fibers, when DVM FCs are eliminated
      prior to fusion. When these cells are also eliminated, myogenesis fails to occur.
      In the second set of studies, targeted expression of constitutively active
      Ras(V12) also resulted in the appearance of supernumerary fibers. In this case,
      the original DVM FCs are present, suggesting alterations in cell fate. Taken
      together, these data suggest that DVM myoblasts are able to respond to cues other
      than the original founder cell, to initiate fusion and fiber formation. Thus, the
      role of the large DVM founder cells is to generate the correct number of fibers,
      but they are not required for fiber formation itself. We also present evidence
      that the DVM FCs may arise from the leg imaginal disc.

PMID- 18616938
TI  - Evaluation of Polo-like Kinase 1 inhibition on the G2/M checkpoint in Acute
      Myelocytic Leukaemia.
AB  - Polo-Kinase 1 (PLK1) is a key cell cycle regulator that is necessary for
      checkpoint recovery after DNA damage-induced G2 arrest. We have examined the
      effects of PLK inhibition in Acute Myelocytic Leukaemia (AML) cells, whose
      resistance to genotoxic agents is thought to be associated with checkpoint
      reinforcement. We report that in U937 AML cells, PLK1 participates in checkpoint
      recovery, and that inhibition of PLK by the GW843682X compound results in mitotic
      accumulation and apoptosis. We also found that when challenged with VP-16,
      inhibition of PLK1 prevented U937 cells from checkpoint exit. Finally, we found
      that treatment with GW843682X slightly reduced genotoxic-induced inhibition of
      colony formation efficiency of primary leukaemia cells (CFU-L) from AML patients.

PMID- 18616939
TI  - The role of lipoic acid in prevention of nitroglycerin tolerance.
AB  - Besides other organic nitrates, nitroglycerin (glyceryl trinitrate; GTN) has been
      used to treat acute heart failure particularly due to ischemic heart disease.
      However, one of serious clinical problems of the GTN therapy, particularly a long
      standing medication, is hemodynamic tolerance to GTN, manifested by the decreased
      therapeutic efficacy of the drug. The most recent studies have suggested that
      mitochondrial lipoate/dihydrolipoate system-dependent aldehyde dehydrogenase-2
      plays a key role in nitric oxide release from GTN. The aldehyde dehydrogenase-2
      performs three enzymatic activities of dehydrogenase, esterase and reductase. The
      reductase activity is responsible for bioactivation of organic nitrates, such as
      GTN yielding nitrite and dinitrate (1,2-GDN/1,3-GDN, approximately 8:1). In view
      of a large contribution of dihydrolipoic acid to stabilization and regeneration
      of thiol groups, necessary for the reductase activity of aldehyde dehydrogenase
      2, we conducted studies aimed to determine whether lipoic acid administration to
      rats is able to prevent GTN tolerance. The studies were conducted on 4 groups of
      animals: control saline-treated, model GTN-tolerant, GTN + lipoic acid-treated,
      lipoic acid alone-administered groups. On the 9th day of experiment animals were
      given i.v. therapeutic dose of GTN. We measured in all animals systolic and
      diastolic blood pressure before injection of therapeutic dose of GTN into the
      cadual vein and during 20 min thereafter. Levels of nitric oxide and reactive
      oxygen species and activities of glutathione peroxidase and superoxide dismutase
      were assayed in the aorta, plasma and heart of all animals. In addition, levels
      of malondialdehyde, and non-protein thiols, and activities of glutathione S
      transferase and gamma-glutamyl transpeptidase were evaluated in the heart and
      plasma. The obtained results indicate that treatment of rats with a combination
      of lipoic acid and GTN can efficiently counteract GTN tolerance.

PMID- 18616940
TI  - Resveratrol protects primary rat hepatocytes against oxidative stress damage:
      activation of the Nrf2 transcription factor and augmented activities of
      antioxidant enzymes.
AB  - Oxidative stress is recognized as an important factor in the development of liver
      pathologies. The reactive oxygen species endogenously generated or as a
      consequence of xenobiotic metabolism are eliminated by enzymatic and nonenzymatic
      cellular systems. Besides endogen defences, the antioxidant consumption in the
      diet has an important role in the protection against the development of diseases
      product of oxidative damage. Resveratrol is a naturally occurring compound which
      is part of the human diet. This molecule has been shown to have many biological
      properties, including antioxidant activity. We decided to test if resveratrol
      could protect primary hepatocytes in culture from oxidative stress damage and if
      so, to determine if this compound affects the cellular detoxifying systems and
      their regulation through the Nrf2 transcription factor that regulates the
      expression of antioxidant and phase II detoxifying enzymes. Cell death by
      necrosis was detected by measuring the activity of lactate dehydrogenase
      liberated to the medium. The activities of antioxidant and phase II enzymes were
      measured using previously described methods. Activation of the Nrf2 transcription
      factor was studied by confocal microscopy and the Nrf2 and its coding mRNA levels
      were determined by western blot and quantitative PCR respectively. Resveratrol
      pre-treatment effectively protected hepatocytes in culture exposed to oxidative
      stress, increasing the activities of catalase, superoxide dismutase, glutathione
      peroxidase, NADPH quinone oxidoreductase and glutathione-S-transferase.
      Resveratrol increases the level of Nrf2 and induces its translocation to the
      nucleus. Also, it increases the concentration of the coding mRNA for Nrf2. In
      this work we show that resveratrol could be a useful drug for the protection of
      liver cells from oxidative stress induced damage.

PMID- 18616941
TI  - Nitric oxide enhances Oct-4 expression in bone marrow stem cells and promotes
      endothelial differentiation.
AB  - This study was designed to investigate the role of nitric oxide (NO) in bone
      marrow stem cells and their differentiation into endothelial cells in vitro.
      Adult mouse bone marrow multipotent progenitor cells (MAPCs) were used as the
      source of stem cells. Oct-4 expression (both mRNA and protein) was significantly
      increased by up to 68.0% in MAPCs when incubated with NO donors DETA-NONOate or
      sodium nitroprusside (SNP) in a concentration-dependant manner (n=3, P<0.05).
      However, the cell proliferation was dramatically decreased by over 3-folds when
      treated with DETA-NONOate or SNP for 48 h (n=3, P<0.05). When MAPCs were exposed
      to DETA-NONOate (100 microM) for the first 48 h during differentiation, the
      expression (both mRNA and protein) of vWF was significantly increased at day 14
      in the differentiating cells. The effects of DETA-NONOate or SNP on cell
      proliferation, Oct-4 expression and endothelial differentiation of MAPCs were not
      affected by the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin
      1-one or cGMP analog 8-Br-cGMP. These data indicate that NO may regulate both the
      pluripotency and differentiation of MAPCs via a cGMP-independent mechanism.

PMID- 18616942
TI  - Aliphatic beta-nitro alcohols for non-enzymatic collagen cross-linking of scleral
      tissue.
AB  - The success of riboflavin photochemical cross-linking of the cornea in treating
      keratoconus and post-surgical keratectasia has prompted interest in cross-linking
      scleral tissue with a potential application to stabilize myopic progression.
      Applying an UVA light source to the sclera is difficult, particularly in the
      posterior region. An alternate pharmacologic approach to scleral cross-linking
      may be possible. The present study was undertaken in order to identify nitrite
      related compounds capable of inducing scleral tissue cross-linking and to gain
      information regarding the possible chemical mechanisms involved. 8x4 mm strips of
      porcine and human sclera were incubated in various concentrations of nitrite
      related agents (1-100mM) at 37 degrees C. pH 7.4 was used for all experiments
      except those involving NaNO(2). Following a 24-96 h incubation period, the
      samples were tested for cross-linking effects using thermal shrinkage temperature
      (T(s)) analysis. Several compounds were studied including NaNO(2), 2
      nitroethanol, 2-nitro-1-propanol, 3-nitro-2-pentanol, 2-nitrophenol, 2
      nitroethane, 2-aminoethanol, isopentyl nitrite, DPTA/NO, DETA/NO, and urea, a
      nitrous acid trap. The results indicate that short chain aliphatic beta-nitro
      alcohols (2-nitroethanol, 2-nitro-1-propanol, and 3-nitro-2-pentanol) are
      particularly effective cross-linking agents at pH 7.4, showing both time and
      concentration dependent effects. Furthermore, nitrosation does not appear to
      induce tissue cross-linking. In conclusion, aliphatic beta-nitro alcohols can
      cross-link scleral tissue at physiologic pH and temperature. Since beta-nitro
      alcohols are known to have reasonable toxicity profiles, these agents could find
      utility as pharmacologic cross-linking agents for scleral thinning disease.

PMID- 18616943
TI  - Phosphorylation of U24 from Human Herpes Virus type 6 (HHV-6) and its potential
      role in mimicking myelin basic protein (MBP) in multiple sclerosis.
AB  - Myelin basic protein (MBP) from multiple sclerosis (MS) patients contains lower
      levels of phosphorylation at Thr97 than normal individuals. The significance of
      phosphorylation at this site is not fully understood, but it is proposed to play
      a role in the normal functioning of MBP. Human Herpesvirus Type 6 encodes the
      protein U24, which has tentatively been implicated in the pathology of MS. U24
      shares a 7 amino acid stretch encompassing the Thr97 phosphorylation site of MBP:
      PRTPPPS. We demonstrate using a combination of mass spectrometry, thin layer
      chromatography and autoradiography, that U24 can be phosphorylated at the
      equivalent threonine. Phospho-U24 may confound signalling or other pathways in
      which phosphorylated MBP may participate, precipitating a pathological process.

PMID- 18616944
TI  - The impact of hospital-acquired infection on outcome in acute pancreatitis.
AB  - BACKGROUND & AIMS: Little is known regarding the impact of hospital-acquired
      infection (HAI) in acute pancreatitis (AP). We conducted a population-based
      assessment of the impact of HAI on outcome in AP. METHODS: Patient data were
      obtained from the Cardinal Health Clinical Outcomes Research Database, a large
      population-based data set. Cases with principal diagnosis by International
      Classification of Diseases, ninth revision, clinical modification 577.0 (AP)
      between January 2004 and January 2005 were identified. These cases were linked
      with recently reported HAI data collected by the Pennsylvania Health Care Cost
      Containment Council. Identification of HAI was based on definitions set forth by
      the National Nosocomial Infection Surveillance System. We conducted a 5:1
      multivariate propensity-matched cohort study to determine the independent
      contribution of HAI to in-hospital mortality, length of stay (LOS), and hospital
      charges. RESULTS: From 177 participating hospitals, there were 11,046 AP cases
      identified. Eighty-two (0.7%) patients developed an HAI. Mortality in the overall
      AP population was 1.2% vs 11.4% among 405 matched non-HAI controls vs 28.4% among
      patients who developed HAI (chi(2) test, P < .0001). Fifteen percent of all
      deaths was associated with an HAI. Both average LOS and hospital charges were
      significantly increased among patients with HAI compared with matched non-HAI
      controls. CONCLUSIONS: We determined that HAI had a major impact on mortality in
      AP. Patients who developed HAI also had significantly increased LOS and hospital
      charges. These differences were not explained by increased disease severity
      alone. Reducing HAI is an important step to improving outcome in AP.

PMID- 18616945
TI  - Direct versus indirect action of cholecystokinin on human pancreatic acinar
      cells: is it time for a judgment after a century of trial?

PMID- 18616946
TI  - Electronic clinical challenges and images in GI. Pneumatosis cystoides
      intestinalis.

PMID- 18616947
TI  - Denatured-state energy landscapes of a protein structural database reveal the
      energetic determinants of a framework model for folding.
AB  - Position-specific denatured-state thermodynamics were determined for a database
      of human proteins by use of an ensemble-based model of protein structure. The
      results of modeling denatured protein in this manner reveal important sequence
      dependent thermodynamic properties in the denatured ensembles as well as
      fundamental differences between the denatured and native ensembles in overall
      thermodynamic character. The generality and robustness of these results were
      validated by performing fold-recognition experiments, whereby sequences were
      matched with their respective folds based on amino acid propensities for the
      different energetic environments in the protein, as determined through cluster
      analysis. Correlation analysis between structure and energetic information
      revealed that sequence segments destined for beta-sheet in the final native fold
      are energetically more predisposed to a broader repertoire of states than are
      sequence segments destined for alpha-helix. These results suggest that within the
      subensemble of mostly unstructured states, the energy landscapes are dominated by
      states in which parts of helices adopt structure, whereas structure formation for
      sequences destined for beta-strand is far less probable. These results support a
      framework model of folding, which suggests that, in general, the denatured state
      has evolutionarily evolved to avoid low-energy conformations in sequences that
      ultimately adopt beta-strand. Instead, the denatured state evolved so that
      sequence segments that ultimately adopt alpha-helix and coil will have a high
      intrinsic structure formation capability, thus serving as potential nucleation
      sites.

PMID- 18616949
TI  - In vitro multimerization and membrane insertion of bacterial outer membrane
      secretin PulD.
AB  - Synthesis of the Klebsiella oxytoca outer membrane secretin PulD, or its membrane
      associated core domain, in a liposome-supplemented Escherichia coli in vitro
      transcription-translation system resulted in the formation of multimers that
      appeared as typical dodecameric secretin rings when examined by negative-stain
      electron microscopy. Cryo-electron microscopy of unstained liposomes and
      differential extraction by urea indicated that the secretin particles were
      inserted into the liposome membranes. When made in the presence of the detergent
      Brij-35, PulD and the core domain were synthesized as monomers. Both proteins
      caused almost immediate growth cessation when synthesized in E. coli without a
      signal peptide. The small amounts of PulD synthesized before cell death appeared
      as multimers with characteristics similar to those of the normal outer membrane
      secretin dodecamers. It was concluded that multimerization and membrane insertion
      are intrinsic properties of secretin PulD that are independent of a specific
      membrane environment or membrane-associated factors. The closely related Erwinia
      chrysanthemi secretin OutD behaved similarly to PulD in all assays, but the more
      distantly related Neisseria meningitidis secretin PilQ did not form multimers
      either when made in vitro in the presence of liposomes or when made in E. coli
      without its signal peptide. This is the first report of the apparently
      spontaneous in vitro assembly and membrane insertion of a large outer membrane
      protein complex. Spontaneous multimerization and insertion appear to be
      restricted to outer membrane proteins closely related to PulD.

PMID- 18616948
TI  - Molecular determinants for the interaction of human neutrophil alpha defensin 1
      with its propeptide.
AB  - Human neutrophil alpha-defensins (HNPs) are cationic antimicrobial peptides that
      are synthesized in vivo as inactive precursors (proHNPs). Activation requires
      proteolytic excision of their anionic N-terminal inhibitory pro peptide. The pro
      peptide of proHNP1 also interacts specifically with and inhibits the
      antimicrobial activity of HNP1 inter-molecularly. In the light of the opposite
      net charges segregated in proHNP1, functional inhibition of the C-terminal
      defensin domain by its propeptide is generally thought to be of electrostatic
      nature. Using a battery of analogs of the propeptide and of proHNP1, we
      identified residues in the propeptide region important for HNP1 binding and
      inhibition. Only three anionic residues in the propeptide, Glu(15), Asp(20) and
      Glu(23), were modestly important for interactions with HNP1. By contrast, the
      hydrophobic residues in the central part of the propeptide, and the conserved
      hydrophobic motif Val(24)Val(25)Val(26)Leu(28) in particular, were critical for
      HNP1 binding and inhibition. Neutralization of all negative charges in the
      propeptide only partially activated the bactericidal activity of proHNP1. Our
      data indicate that hydrophobic forces have a dominant role in mediating the
      interactions between HNP1 and its propeptide--a finding largely contrasting the
      commonly held view that the interactions are of an electrostatic nature.

PMID- 18616950
TI  - Molecular evolution of the HBII-52 snoRNA cluster.
AB  - HBII-52 is a human brain-specific C/D box snoRNA that potentially regulates the
      editing and/or alternative splicing of the serotonin receptor. Forty-two nearly
      identical copies of the HBII-52 gene are located immediately downstream of the
      SNRPN protein-coding gene in an imprinted locus associated with Prader-Willi
      syndrome. Other eutherian mammals, with genomic assemblies covering the
      corresponding locus, also have multiple orthologous copies of HBII-52. The SNRPB
      gene, which is known to have given rise to SNRPN through gene duplication,
      expresses a C/D box snoRNA, SNORD119, from its fifth intron. Here we show that,
      despite the fact that they lie in different positions relative to the orthologous
      SNRPB/SNRPN coding sequences, there are significant sequence similarities between
      SNORD119 and HBII-52, including the antisense element and the stem-forming
      regions. By analysing these snoRNAs in marsupial and eutherian mammal genomes, we
      reconstruct the likely evolutionary history of the HBII-52 cluster and SNORD119
      and suggest that they have evolved from a common ancestor.

PMID- 18616951
TI  - Kinetics of fibril formation of bovine kappa-casein indicate a conformational
      rearrangement as a critical step in the process.
AB  - S-carboxymethylated (SCM) kappa-casein forms in vitro fibrils that display
      several characteristics of amyloid fibrils, although the protein is unrelated to
      amyloid diseases. In order to get insight into the processes that prevent the
      formation of amyloid fibrils made of kappa-caseins in milk, we have characterized
      in detail the reaction and the roles of its possible effectors: glycosylation and
      other caseins. Given that native kappa-casein occurs as a heterogeneous mixture
      of carbohydrate-free and carbohydrate-containing chains, kinetics of fibril
      formation were performed on purified glycosylated and unglycosylated SCM kappa
      caseins using the fluorescent dye thioflavin T in conjunction with transmission
      electron microscopy and Fourier transform infrared spectroscopy for morphological
      and structural analyses. Both unglycosylated and glycosylated SCM kappa-caseins
      have the ability to fibrillate. Kinetic data indicate that the fibril formation
      rate increases with SCM kappa-casein concentration but reaches a plateau at high
      concentrations, for both the unglycosylated and glycosylated forms. Therefore, a
      conformational rearrangement is the rate-limiting step in fibril growth of SCM
      kappa-casein. Transmission electron microscopy images indicate the presence of 10
      to 12-nm spherical particles prior to the appearance of amyloid structure.
      Fourier transform infrared spectroscopy spectra reveal a conformational change
      within these micellar aggregates during the fibrillation. Fibrils are helical
      ribbons with a pitch of about 120-130 nm and a width of 10-12 nm. Taken together,
      these findings suggest a model of aggregation during which the SCM kappa-casein
      monomer is in rapid equilibrium with a micellar aggregate that subsequently
      undergoes a conformational rearrangement into a more organized species. These
      micelles assemble and this leads to the growing of amyloid fibrils. Addition of
      alpha(s1)-and beta-caseins decreases the growth rate of fibrils. Their main
      effect was on the elongation rate, which became close to that of the limiting
      conformation change, leading to the appearance of a lag phase at the beginning of
      the kinetics.

PMID- 18616952
TI  - Human neutrophil-pulmonary microvascular endothelial cell interactions in vitro:
      differential effects of nitric oxide vs. peroxynitrite.
AB  - Sepsis-induced acute lung injury is characterized by activation and injury of
      pulmonary microvascular endothelial cells (PMVEC), increased neutrophil-PMVEC
      adhesion and migration, and trans-PMVEC high-protein edema. Inducible NO synthase
      (iNOS) inhibits septic murine neutrophil migration in vivo and in vitro. The
      effects of NO in human neutrophil-PMVEC interactions are not known. We isolated
      human PMVEC using magnetic bead-bound anti-PECAM antibody. Confluent PMVEC at
      passage 3-4 were co-cultured with human neutrophils for assessment of neutrophil
      PMVEC adhesion, and trans-PMVEC neutrophil migration and Evans-Blue dye-labeled
      albumin leak. Two NO donors (spermine-NONOate, S-nitroso-N-acetylpenicillamine)
      attenuated both cytomix-enhanced neutrophil-PMVEC adhesion by 64+/-14% (p<0.01)
      and 32+/-3% (p<0.05), respectively, and cytomix-induced trans-PMVEC neutrophil
      migration by 85+/-16% (p<0.01) and 43+/-5% (p<0.01), respectively.
      Correspondingly, iNOS inhibition with 1400W enhanced cytomix-stimulated
      neutrophil migration by 52+/-3% (p<0.01), but had no effect on neutrophil-PMVEC
      adhesion. Conversely, a peroxynitrite donor (SIN-1) increased both neutrophil
      PMVEC adhesion (38+/-2% vs. 14+/-1% control, p<0.01) and trans-PMVEC neutrophil
      migration; with both effects were completely inhibited by scavenging of NO,
      superoxide, or peroxynitrite (p<0.05 for each). Scavenging of peroxynitrite also
      eliminated cytomix-induced neutrophil adhesion and migration. Blocking CD18
      dependent neutrophil adhesion prevented cytomix-stimulated trans-PMVEC EB-albumin
      leak (p<0.05), while inhibiting neutrophil migration paradoxically enhanced
      cytomix-stimulated EB-albumin leak (11+/-1% vs. 7+/-0.5%, p<0.01). FMLP-induced
      neutrophil migration had no effect on trans-PMVEC EB-albumin leak. In summary, we
      report differential effects, including the inhibitory action of NO and
      stimulatory effect of ONOO(-) on human neutrophil-PMVEC adhesion and trans-PMVEC
      migration under cytomix stimulation. Moreover, neutrophil-PMVEC adhesion, but not
      trans-PMVEC migration, contributes to human PMVEC barrier dysfunction.

PMID- 18616953
TI  - Identification of new RECQL4 mutations in Caucasian Rothmund-Thomson patients and
      analysis of sensitivity to a wide range of genotoxic agents.
AB  - Rothmund-Thomson syndrome (RTS), a rare recessive autosomal disorder, presents
      genome instability and clinical heterogeneity with growth deficiency, skin and
      bone defects, premature aging symptoms and cancer susceptibility. A subset of RTS
      patients presents mutations of the RECQL4 gene, member of the RecQ family of DNA
      helicases, including the RECQL2 (BLM) and RECQL3 (WRN) genes, defective in the
      cancer prone Bloom and Werner syndromes, respectively. Analysis of the RECQL4
      gene in six clinically diagnosed RTS patients shows five patients, including two
      siblings, with eight mutations mainly located in the helicase domain, three
      patients presenting two mutations. The alterations include four missense
      mutations, one nonsense mutation and the same frameshift deletion, g.2881delG in
      exon 9 found in three patients. Seven RECQL4 polymorphisms, two being new, have
      also been identified. Primary RTS fibroblasts from these RTS patients show no
      sensitivity to a wide variety of genotoxic agents including ionizing or
      ultraviolet irradiation, nitrogen mustard, 4NQO, 8-MOP, Cis-Pt, MMC, H2O2, HU, or
      UV plus caffeine which could be related to the RECQL4 alterations identified
      here. This is in contrast with the DNA damage sensitive Bloom and Werner cells
      and highlights the complexity of the numerous RecQ protein functions implicated
      in the different cellular pathways required for maintaining genomic integrity.

PMID- 18616954
TI  - Mutagenicity of N-nitrosodiethanolamine in a V79-derived cell line expressing two
      human biotransformation enzymes.
AB  - N-nitrosodiethanolamine (NDELA) has demonstrated carcinogenic activity in various
      rodent models. However, it is negative or only weakly active in standard in vitro
      genotoxicity assays. This poor response might be due to the requirement of
      specific enzymes for its activation. Previous work indicated that cytochrome P450
      (CYP) 2E1, alcohol dehydrogenases and sulphotransferases (SULTs) can convert
      NDELA into reactive metabolites. We report here that NDELA induces concentration
      dependent gene mutations (at the hprt locus) in V79-hCYP2E1-hSULT1A1 cells,
      engineered for expression of human CYP2E1 and human SULT1A1, but is inactive in
      parental V79 cells. Mutagenicity of NDELA in V79-hCYP2E1-hSULT1A1 cells was
      abolished by the CYP2E1 inhibitor 1-aminobenzotriazole, but unaffected by the
      SULT1A1 inhibitor pentachlorophenol. The efficiency and specificity of these
      inhibitors was demonstrated in gene mutation assays using SULT- and CYP2E1
      dependent reference mutagens, 2-nitropropane and N-nitrosodimethylamine,
      respectively. In this study, it is documented for the first time that NDELA can
      induce gene mutations in mammalian cells. Whereas human CYP2E1 was required for
      its activation, human SULT1A1 was not involved either in its activation or its
      inactivation in our cell model.

PMID- 18616955
TI  - Role of metabotropic glutamate receptors in the control of neuroendocrine
      function.
AB  - Glutamate exerts its effects through binding and activation of two classes of
      specific receptors: ionotropic (iGluRs) and metabotropic (mGluRs). Group I mGluR
      includes mGluR1 and mGluR5 subtypes, group II includes mGluR2 and mGluR3 subtypes
      and group III includes the subtypes mGluR 4, 6, 7 and 8. Glutamate and its
      receptors are found in all key hypothalamic areas critically involved in
      reproduction and neuroendocrine function. To date, considerable data support an
      important role for iGluRs in the control of neuroendocrine function; however, the
      role of mGluRs as regulators of hypothalamic-pituitary function has not been
      clearly elucidated. mGluRs could be exerting a fine tune on the release of
      hypothalamic factors that regulate hormone release such as Substance P, GABA,
      alpha-MSH and CRH. Group II mGluR exert a direct inhibitory effect on anterior
      pituitary prolactin and GH secretion. Moreover, some group II mGluR agonists,
      like LY 354,740 and LY 379,268, can modulate PRL secretion from the anterior
      pituitary through their actions as dopamine receptor agonists. Evidence suggests
      a role for group III mGluR subtypes in stress-related behavioral disorders.
      Several reports indicate that selective ligands for mGluR subtypes have potential
      for the treatment of a wide variety of neurological and psychiatric disorders,
      including depression, anxiety disorders, schizophrenia, epilepsy and Alzheimer's
      disease among others. Since converging lines of evidence suggest a role for
      mGluRs subtypes in neuroendocrine regulation of hormone secretion, mGluRs
      neuroendocrine actions must be taken in consideration to insure proper treatment
      of these diseases. Moreover, discovery of selective agonists provides an
      opportunity to investigate the physiological role of mGluR subtypes and to
      directly test the neuroendocrine actions of mGluRs. Finally, mGluRs selective
      agonists may have an impact in the treatment of conditions involving chronic
      stress, such as depression and anxiety disorders, since they regulate
      neuroendocrine stress circuits involving the HPA axis and stress-sensitive
      hormones such as oxytocin and prolactin. This review aims to provide a survey of
      our current understanding of the effects of mGluR activation on neuroendocrine
      function.

PMID- 18616956
TI  - The analgesic effect of N-arachidonoyl-serotonin, a FAAH inhibitor and TRPV1
      receptor antagonist, associated with changes in rostral ventromedial medulla and
      locus coeruleus cell activity in rats.
AB  - We evaluated the effects of intra-periaqueductal grey (PAG) N-arachidonoyl
      serotonin (AA-5-HT), a compound with a "dual" ability to inhibit the fatty acid
      amide hydrolase (FAAH) and to antagonize transient receptor vanilloid type 1
      (TRPV1) receptors, on endocannabinoid levels, rostral ventromedial medulla (RVM)
      ON and OFF cell activities, thermal nociception (tail flick in anaesthetized
      rats) and formalin-induced nocifensive responses in awake rats. AA-5-HT increased
      endocannabinoid levels in the PAG and induced analgesia. Paradoxically, it also
      depressed the RVM OFF cell, as well as the ON cell activities. The effect of AA-5
      HT was mimicked by co-injecting the selective FAAH inhibitor URB597 and the
      selective TRPV1 antagonist I-RTX into the PAG, which also induced analgesia and
      inhibition of ON and OFF cell ongoing activities. The recruitment of
      "alternative" pathways, such as PAG-locus coeruleus (LC)-spinal cord might be
      responsible for AA-5-HT effect since we found evidence that (i) intra-PAG AA-5-HT
      increased LC neuron firing activities, and (ii) intrathecal phentolamine or
      ketanserin prevented the analgesic effect of AA-5-HT. Moreover, intra-PAG AA-5-HT
      prevented the changes in the ON and OFF cells firing activity induced by intra
      paw formalin, and it inverted the formalin-induced increase in LC adrenergic cell
      activity. All AA-5-HT effects were antagonized by cannabinoid CB1 and TRPV1
      receptor antagonists thus suggesting that co-localization of these receptors in
      the PAG can be an appropriate neural substrate for AA-5-HT-induced analgesia.

PMID- 18616957
TI  - Adrenomedullin enhances baroreceptor reflex response via cAMP/PKA signaling in
      nucleus tractus solitarii of rats.
AB  - Adrenomedullin (ADM), a 52-amino acid peptide, elicits differential
      cardiovascular responses when it is administered systemically or directly to the
      brain. We evaluated in the present study the hypothesis that ADM may modulate
      baroreceptor reflex (BRR) response through an ADM receptor-mediated cAMP/ protein
      kinase A (PKA)-dependent mechanism in the nucleus tractus solitarii (NTS), the
      terminal site for primary baroreceptor afferents, using Sprague-Dawley rats. Our
      immunoblot and immunohistochemical results showed that the two component proteins
      of the ADM(1) receptor complex, calcitonin receptor-like receptor (CRLR) and
      receptor activity modifying protein (RAMP)-2, were uniformly distributed and
      highly co-localized in the NTS. Site-specific microinjection of ADM (0.02
      0.2pmol) unilaterally into the NTS significantly increased BRR response and
      sensitivity in a time- and dose-related manner, without affecting arterial
      pressure and heart rate. The BRR enhancing effect of ADM was also temporally
      correlated with an up-regulation of PKA(beta), the active form of PKA and an
      increase in PKA activity. In addition, the ADM-evoked BRR enhancement or PKA
      activation was abolished by co-microinjection with a selective ADM(1) receptor
      antagonist, ADM(22-52), an adenylyl cyclase inhibitor, SQ22536, or a PKA
      inhibitor, Rp-8-bromo-cAMP. These results suggest that ADM enhances BRR via
      activation of a cAMP/PKA-dependent mechanism by acting site-specifically on
      ADM(1) receptors in NTS.

PMID- 18616958
TI  - Cingulate gyral reductions are related to low executive functioning and psychotic
      symptoms in 22q 11.2 deletion syndrome.
AB  - A similar pattern of deficits in executive function and neuroanatomical
      abnormalities is shared between 22q 11.2 deletion syndrome (22q 11DS) and
      schizophrenia, suggesting that common cerebral alterations may lead to cognitive
      dysfunction and promote the appearance of psychotic symptoms in 22q 11DS
      individuals. Specifically, there is increasing evidence for involvement of the
      cingulate gyrus (CG) in executive dysfunction and the expression of positive
      symptoms in schizophrenia. The aim of our study is to examine CG morphology in a
      22q 11DS population and its potential role as a cerebral marker of executive
      dysfunction and the manifestation of psychotic symptoms. Using region of interest
      (ROI)-based analysis, we compared CG volumes from 58 children and adults affected
      by 22q 11DS with 64 healthy age- and gender-matched controls. After covarying for
      total cranium grey matter and age, a bilateral reduced CG grey matter volume,
      driven by a decrease in anterior CG cortex, was observed among 22q 11DS patients.
      Further post hoc analyses suggest correlations between right CG cortical
      reductions, low-executive functioning and the occurrence of psychotic symptoms.
      The CG structural abnormalities observed in 22q 11DS are consistent with previous
      reports in schizophrenic patients and are associated with pre-morbid cognitive
      impairments. The mechanisms by which these changes may modulate executive
      functioning and the expression of psychosis are discussed.

PMID- 18616959
TI  - Synthesis of 4-azasteroids by an intramolecular Ugi reaction.
AB  - In this paper we report the use of an intramolecular Ugi reaction to synthesize
      new 4-azacholestanes diversely substituted both at N-4 and C-5. Both the scope
      and the stereochemical outcome of this approach were studied by varying the
      nature of the components necessary for this multicomponent reaction. In sight of
      our results we concluded that this methodology can be applied to obtain 4
      azasteroids targeted to find new biologically active compounds.

PMID- 18616960
TI  - 2-methylene-19-nor-20(S)-1alpha-hydroxy-bishomopregnacalciferol [20(S)-2MbisP],
      an analog of vitamin D3 [1,25(OH)2D3], does not stimulate intestinal phosphate
      absorption at levels previously shown to suppress parathyroid hormone.
AB  - Chronic kidney disease results in a reduction in 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3) synthesis and an accumulation of phosphorus in the blood, leading
      to secondary hyperparathyroidism and renal osteodystrophy. Vitamin D analogs that
      retain the ability to suppress PTH but that are less calcemic and phosphatemic
      than the native hormone are preferred therapies for secondary
      hyperparathyroidism. However, even the most favored analog currently approved for
      the treatment of chronic kidney disease patients, i.e. 1,25-dihydroxy-19-nor
      vitamin D2 (19-nor-D2, Zemplar), still retains some ability to stimulate
      intestinal absorption of calcium and phosphate. A recently described analog of
      vitamin D3, 2-methylene-19-nor-20(S)-1alpha-hydroxy-bishomopregnacalciferol
      [20(S)-2MbisP], suppresses PTH levels, but is unable to stimulate intestinal
      calcium absorption or bone resorption in rats. The present study shows that 20(S)
      2MbisP is unable to stimulate intestinal phosphate absorption at levels known to
      suppress PTH secretion. Further, 19-nor-vitamin D2 under the same circumstances
      does stimulate phosphate absorption. Thus, 2MbisP has significant potential in
      the management of secondary hyperparathyroidism of renal failure.

PMID- 18616961
TI  - Molecular and cellular analysis of B-cell populations in the rainbow trout using
      Pax5 and immunoglobulin markers.
AB  - To date, the trout B-cell is poorly defined, as many essential molecular markers
      are not yet available for this species. In mammalian systems, the transcription
      factor Pax5, expressed from pre-B through plasmablast stages, provides an
      important marker for B-cell differentiation. In a previous study we showed that
      Pax5 is expressed in the trout. Here we identify trout B-cell populations that
      vary in expression of Pax5, membrane and secreted Ig. Immune tissues were
      separated based on concentration of surface IgM, and analyzed by qPCR and flow
      cytometry. Results suggest that spleen and PBL contain mostly resting B cells,
      which lack secreted Ig. While the great majority of splenic B cells become
      strongly activated upon LPS stimulation, PBLs do not. Additionally, anterior
      kidney contains both developing B and Ig-secreting B-cell populations, but few
      resting, mature B cells. Lastly, posterior kidney contains multiple B-cell
      populations in various states of activation. We conclude that trout immune
      tissues contain multiple, developmentally diverse and tissue-specific B-cell
      populations as defined by their relative expression of Pax5, surface IgM, and
      secreted IgM.

PMID- 18616963
TI  - The hERG potassium channel and hERG screening for drug-induced torsades de
      pointes.
AB  - Drug-induced torsades de pointes (TdP) arrhythmia is a major safety concern in
      the process of drug design and development. The incidence of TdP tends to be low,
      so early pre-clinical screens rely on surrogate markers of TdP to highlight
      potential problems with new drugs. hERG (human ether-a-go-go-related gene,
      alternative nomenclature KCNH2) is responsible for channels mediating the 'rapid'
      delayed rectifier K+ current (IKr) which plays an important role in ventricular
      repolarization. Pharmacological inhibition of native IKr and of recombinant hERG
      channels is a shared feature of diverse drugs associated with TdP. In vitro hERG
      assays therefore form a key element of an integrated assessment of TdP liability,
      with patch-clamp electrophysiology offering a 'gold standard'. However, whilst
      clearly necessary, hERG assays cannot be assumed automatically to provide
      sufficient information, when considered in isolation, to differentiate 'safe'
      from 'dangerous' drugs. Other relevant factors include therapeutic plasma
      concentration, drug metabolism and active metabolites, severity of target
      condition and drug effects on other cardiac ion channels that may mitigate or
      exacerbate effects of hERG blockade. Increased understanding of the nature of
      drug-hERG channel interactions may ultimately help eliminate potential hERG
      blockade early in the design and development process. Currently, for promising
      drug candidates integration of data from hERG assays with information from other
      pre-clinical safety screens remains essential.

PMID- 18616964
TI  - B-type natriuretic peptide (BNP) attenuates the L-type calcium current and
      regulates ventricular myocyte function.
AB  - A fundamental question in physiology is how hormones regulate the functioning of
      a cell or organ. It was therefore the aim of this study to investigate the
      effect(s) of BNP-32 on calcium handling by ventricular myocytes obtained from the
      rat left ventricle. We specifically tested the hypothesis that BNP-32 decreased
      the L-type calcium current (I(Ca,L)). Perforated patch clamp technique was used
      to record I(Ca,L) and action potential (AP) in voltage and current clamp mode,
      respectively. Myocyte shortening was measured using a photodiode array edge
      detection system and intracellular calcium transients were measured by
      fluorescence photometry. Western blotting was used to determine the relative
      change in the expression of proteins. At the concentrations tested, BNP-32
      significantly decreased cell shortening in a dose-dependent manner; increased the
      phase II slope of the AP by 53.0%; increased the APD(50) by 16.9%; reduced the
      I(Ca,L) amplitude with a 22.9% decrease in the peak amplitude and reduced Ca(2+)
      dependent inactivation; increased the V(1/2) activation of the L-type calcium
      channel by 51.1% and decreased V(1/2) inactivation by 31.8%; and, intracellular
      calcium transient amplitude was significantly decreased by 32.0%, whereas the
      time to peak amplitude and T(1/2) were both significantly increased by 38.7% and
      89.4% respectively. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein
      expression was reduced by BNP-32. These data suggest that BNP-32 regulates
      ventricular myocyte function by attenuating I(Ca,L), altering the AP and reducing
      SERCA2a activity and/or expression. This study suggests a novel constitutive
      mechanism for the autocrine action of BNP on the L-type calcium channel in
      ventricular myocytes.

PMID- 18616966
TI  - Oligonucleotide sequences forming short self-complimentary hairpins can expedite
      the down-regulation of Coprinopsis cinerea genes.
AB  - Gene silencing in fungi is often induced by dsRNA hairpin forming constructs the
      preparation of which can require multiple cloning steps. To simplify gene
      silencing in the filamentous fungi we have evaluated a high throughput cloning
      method for target sequences using the homobasidiomycete Coprinopsis cinerea, the
      GFP reporter and a commercially available vector system. The pSUPER RNAi System,
      which was developed for mammalian experiments, exploits the human H1 Polymerase
      III (Pol III) RNA gene promoter and expedites cloning/expression of specific user
      defined oligonucleotide sequences to form short self-complimentary hairpins.
      Transformation of C. cinerea with pSUPER constructs harboring specific
      oligonucleotides (19 nt stem length) enabled recovery of transformants with
      reduced transcripts of the GFP transgene, that were less fluorescent in protein
      assays and microscopic phenotypes. This technological advance should expedite
      functional genomic studies in C. cinerea and has wider potential for utility in
      other homobasidiomycete and filamentous fungi.

PMID- 18616965
TI  - Pondering the puzzle of PML (promyelocytic leukemia) nuclear bodies: can we fit
      the pieces together using an RNA regulon?
AB  - The promyelocytic leukemia protein PML and its associated nuclear bodies are hot
      topics of investigation. This interest arises for multiple reasons including the
      tight link between the integrity of PML nuclear bodies and several disease states
      and the impact of the PML protein and PML nuclear bodies on proliferation,
      apoptosis and viral infection. Unfortunately, an understanding of the molecular
      underpinnings of PML nuclear body function remains elusive. Here, a general
      overview of the PML field is provided and is extended to discuss whether some of
      the basic tenets of "PML-ology" are still valid. For instance, recent findings
      suggest that some components of PML nuclear bodies form bodies in the absence of
      the PML protein. Also, a new model for PML nuclear body function is proposed
      which provides a unifying framework for its effects on diverse biochemical
      pathways such as Akt signaling and the p53-Mdm2 axis. In this model, the PML
      protein acts as an inhibitor of gene expression post-transcriptionally via
      inhibiting a network node in the eIF4E RNA regulon. An example is given for how
      the PML RNA regulon model provided the basis for the development of a new anti
      cancer strategy being tested in the clinic.

PMID- 18616967
TI  - The Genome Sequencer FLX System--longer reads, more applications, straight
      forward bioinformatics and more complete data sets.
AB  - The Genome Sequencer FLX System (GS FLX), powered by 454 Sequencing, is a next
      generation DNA sequencing technology featuring a unique mix of long reads,
      exceptional accuracy, and ultra-high throughput. It has been proven to be the
      most versatile of all currently available next-generation sequencing
      technologies, supporting many high-profile studies in over seven applications
      categories. GS FLX users have pursued innovative research in de novo sequencing,
      re-sequencing of whole genomes and target DNA regions, metagenomics, and RNA
      analysis. 454 Sequencing is a powerful tool for human genetics research, having
      recently re-sequenced the genome of an individual human, currently re-sequencing
      the complete human exome and targeted genomic regions using the NimbleGen
      sequence capture process, and detected low-frequency somatic mutations linked to
      cancer.

PMID- 18616968
TI  - Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer
      patients during vaccination with p53-peptide loaded dendritic cells and low-dose
      interleukin-2.
AB  - We have previously established a cancer vaccine using autologous DCs, generated
      by in vitro stimulation with IL-4 and GM-CSF, and pulsed with six HLA-A*0201
      binding wild-type p53 derived peptides. This vaccine was used in combination with
      low-dose interleukin-2 in a recently published clinical Phase II trial where 26
      HLA-A2+ patients with progressive late-stage metastatic breast cancer (BC) were
      included. Almost 1/3rd of the patients obtained stable disease or minor
      regression during treatment with a positive correlation to tumour over-expression
      of p53. In the present study, we performed a comprehensive analysis of the
      effector stage of the p53-specific CD8+ T cells by the use of Dextramer
      Technology and multicolour FACS. Pre- and post-treatment blood samples from eight
      BC patients were analysed. Independent of clinical outcome p53-specific T cells
      were phenotypic distinctly antigen experienced (CD44high, CCR-7low and CD62Llow).
      Furthermore, fresh blood from 18 cancer patients included in the vaccination
      trial were prospectively examined for more general treatment associated
      quantitative and qualitative changes in T cell subpopulations. We found that the
      frequency of CD4+ CD25high regulatory T cells was almost doubled after only 4
      weeks of weekly vaccination and low-dose IL-2. In addition, a decrease in the
      percentage of CD27highCCR-7high CD4/CD8 naive T cells was measured particularly
      in patients with progressive disease during vaccination. Finally, prior to
      immunotherapy a higher percentage of both CD28 and CD27 positive CD8naive/early
      effector memory T cells were present in chemotherapy-treated patients.

PMID- 18616962
TI  - Diabetic neuropathy: mechanisms to management.
AB  - Neuropathy is the most common and debilitating complication of diabetes and
      results in pain, decreased motility, and amputation. Diabetic neuropathy
      encompasses a variety of forms whose impact ranges from discomfort to death.
      Hyperglycemia induces oxidative stress in diabetic neurons and results in
      activation of multiple biochemical pathways. These activated pathways are a major
      source of damage and are potential therapeutic targets in diabetic neuropathy.
      Though therapies are available to alleviate the symptoms of diabetic neuropathy,
      few options are available to eliminate the root causes. The immense physical,
      psychological, and economic cost of diabetic neuropathy underscore the need for
      causally targeted therapies. This review covers the pathology, epidemiology,
      biochemical pathways, and prevention of diabetic neuropathy, as well as discusses
      current symptomatic and causal therapies and novel approaches to identify
      therapeutic targets.

PMID- 18616969
TI  - Comparative remission rates of schizophrenic patients using various remission
      criteria.
AB  - RATIONALE: New standardized criteria for remission in schizophrenia were
      presented in 2005 which need to be examined in regard to their significance for
      clinical trials. OBJECTIVES AND METHODS: Data of six antipsychotic drug trials
      (n=2463) were analyzed by evaluating the proportion of participants who meet the
      new remission criteria, their symptomatic components, other criteria for
      remission and simple response-measures (at least 50% Brief Psychiatric Rating
      Scale (BPRS) reduction and an at least 50% PANSS reduction or a CGI-severity
      score of "mild or better"). RESULTS: A total of 23.3%/27.2% (last-observation
      carried-forward (LOCF)/completer analysis (CO)) of the patients with positive
      symptoms at baseline met the severity criteria of remission at 4 weeks,
      10.5%/20.3% (worst case/CO) met the severity and time criteria at 28 weeks (three
      studies) and 10.9%/32.4% (worst case/CO) met the severity and time criteria at 52
      weeks (one study). At 4 weeks 4.5%/5.5% (LOCF/CO) met the severity criteria when
      a more stringent severity threshold of "very mild or better" was applied. Absence
      of symptoms was attained only sporadically. The psychotic symptoms component was
      met by fewer patients than the negative component. The criteria were more
      stringent than "at least 50% BPRS reduction" and "CGI-severity score not more
      than mild" and--for the long-term results--than "at least 50% PANSS reduction".
      In the short-term analysis, the criteria were less stringent than "at least 50%
      PANSS reduction". CONCLUSIONS: The applicability of the severity component of the
      new criteria in clinical trials was confirmed. The time criterion remains
      difficult to evaluate.

PMID- 18616970
TI  - Cancer initiating properties of fumonisin B1 in a short-term rat liver
      carcinogenesis assay.
AB  - The nature of cancer initiation by fumonisin B(1) (FB(1)) was investigated in rat
      liver by monitoring the effect of phenobarbital (PB) as cancer promoter and
      evaluating the involvement of spontaneously initiated cells. A PB promoting
      regimen (0.05% in the diet) stimulated the outgrowth of FB(1)-induced placental
      glutathione S-transferase (GSTP) positive initiated hepatocytes. Reversion of the
      FB(1)-induced GSTP(+) foci was noticed in the absence of a promoting regimen.
      Younger rats were shown to be more sensitive to the induction of GSTP(+) foci by
      FB(1). Cancer initiation by FB(1) was associated with a hepatotoxic effect, which
      was less pronounced in older rats presumably due to a reduced intake. A specific
      role of spontaneously initiated cells and their promotion by FB(1) into the
      development of eosinophilic clear cell foci could not be established under the
      present experimental conditions. The ability of different stimuli to selectively
      promote the outgrowth of FB(1) initiated cells further verifies the cancer
      initiating potency of this apparent non-genotoxic mycotoxin. The underlying
      mechanism(s) involved in the genesis of the initiated hepatocytes is not known at
      present.

PMID- 18616972
TI  - Efficient connection strategies in 1D and 2D associative memory models with and
      without displaced connectivity.
AB  - This study examines the performance of sparsely connected associative memory
      models built using a number of different connection strategies, applied to one-
      and two-dimensional topologies. Efficient patterns of connectivity are identified
      which yield high performance at relatively low wiring costs in both topologies.
      Networks with displaced connectivity are seen to perform particularly well. It is
      found that two-dimensional models are more tolerant of variations in connection
      strategy than their one-dimensional counterparts; though networks built with both
      topologies become less so as their connection density is decreased.

PMID- 18616973
TI  - A network cell with molecular agents that divides from centrosome signals.
AB  - A novel model of network artificial chemistry (NAC) in which molecular agents
      with assembler programs move through the network is presented. By the execution
      of the agent programs, nodes rewire edges according to their own types (either
      hydrophilic or hydrophobic), and as a consequence, a global topological structure
      is created in the network. Using numerical experiments equipped with three agent
      types (centrosome, hydrogen, and van der Waals), it is demonstrated that the
      revised NAC is able to emulate the organization of a pseudo-lattice structure
      between hydrophilic nodes, repulsion between hydrophilic and hydrophobic nodes,
      and the division of a network cell actualized as a hydrophilic cluster.

PMID- 18616974
TI  - A real-time spiking cerebellum model for learning robot control.
AB  - We describe a neural network model of the cerebellum based on integrate-and-fire
      spiking neurons with conductance-based synapses. The neuron characteristics are
      derived from our earlier detailed models of the different cerebellar neurons. We
      tested the cerebellum model in a real-time control application with a robotic
      platform. Delays were introduced in the different sensorimotor pathways according
      to the biological system. The main plasticity in the cerebellar model is a spike
      timing dependent plasticity (STDP) at the parallel fiber to Purkinje cell
      connections. This STDP is driven by the inferior olive (IO) activity, which
      encodes an error signal using a novel probabilistic low frequency model. We
      demonstrate the cerebellar model in a robot control system using a target
      reaching task. We test whether the system learns to reach different target
      positions in a non-destructive way, therefore abstracting a general dynamics
      model. To test the system's ability to self-adapt to different dynamical
      situations, we present results obtained after changing the dynamics of the
      robotic platform significantly (its friction and load). The experimental results
      show that the cerebellar-based system is able to adapt dynamically to different
      contexts.

PMID- 18616975
TI  - Temporal coding: the relevance of classical activity, its relation to pattern
      frequency bands, and a remark on recoding of excitatory drive into phase shifts.
AB  - We consider an oscillatory network model that is obtained as complex-valued
      generalization of the classical Cohen-Grossberg-Hopfield (CGH) model. Apart from
      a synchronizing mechanism, a stronger and/or more coherent input to a unit in the
      network implies a higher phase velocity of this unit. This constitutes the
      desynchronizing mechanism, referred to as acceleration. The units' activity of
      the classical model translates into the amplitudes of the phase model
      oscillators. This allows to associate classical and temporal coding with
      amplitude and phase dynamics, respectively. We discuss how the two dynamics act
      together to achieve the unambiguous pattern recognition that avoids the
      superposition problem. With respect to coherence, dominating patterns may take
      coherent states also if only a subset of its units is on-state. The competition
      for coherence, introduced by acceleration, realizes a kind of feature counting
      that identifies the dominating pattern as the pattern with the most on-state
      units. This dominating but possibly only partially active pattern may take a
      coherent state with a frequency level that is related to the number of on-state
      units. We also speculate on neurophysiological findings, related to observed
      phase differences between optimally and suboptimally activated neurons, that may
      indicate the presence of acceleration.

PMID- 18616976
TI  - The linearity of emergent spectro-temporal receptive fields in a model of
      auditory cortex.
AB  - The responses of cortical neurons are often characterized by measuring their
      spectro-temporal receptive fields (STRFs). The STRF of a cell can be thought of
      as a representation of its stimulus 'preference' but it is also a filter or
      'kernel' that represents the best linear prediction of the response of that cell
      to any stimulus. A range of in vivo STRFs with varying properties have been
      reported in various species, although none in humans. Using a computational model
      it has been shown that responses of ensembles of artificial STRFs, derived from
      limited sets of formative stimuli, preserve information about utterance class and
      prosody as well as the identity and sex of the speaker in a model speech
      classification system. In this work we help to put this idea on a biologically
      plausible footing by developing a simple model thalamo-cortical system built of
      conductance based neurons and synapses some of which exhibit spike-time-dependent
      plasticity. We show that the neurons in such a model when exposed to formative
      stimuli develop STRFs with varying temporal properties exhibiting a range of
      heterotopic integration. These model neurons also, in common with neurons
      measured in vivo, exhibit a wide range of non-linearities; this deviation from
      linearity can be exposed by characterizing the difference between the measured
      response of each neuron to a stimulus, and the response predicted by the STRF
      estimated for that neuron. The proposed model, with its simple architecture,
      learning rule, and modest number of neurons (<1000), is suitable for
      implementation in neuromorphic analogue VLSI hardware and hence could form the
      basis of a developmental, real time, neuromorphic sound classification system.

PMID- 18616977
TI  - Why metabolic systems are rarely chaotic.
AB  - One of the mysteries surrounding the phenomenon of chaos is that it can rarely be
      found in biological systems. This has led to many discussions of the possible
      presence and interpretation of chaos in biological signals. It has caused
      empirical biologists to be very sceptical of models that have chaotic properties
      or even employ chaos for problem solving tasks. In this paper, it is demonstrated
      that there exists a possible mechanism that is part of the catalytical reaction
      mechanisms which may be responsible for controlling enzymatic reactions such that
      they do not become chaotic. It is proposed that where these mechanisms are not
      present or not effective, chaos may still occur in biological systems.

PMID- 18616978
TI  - Conservation of key members in the course of the evolution of the insulin
      signaling pathway.
AB  - Our understanding of the evolution of the insulin signaling pathway (ISP) is
      still incomplete. One intriguing unanswered question is the explanation of the
      emergence of the glucostatic role of insulin in mammals. To find out whether this
      is due to the development of new sets of signaling transduction elements in these
      organisms, or to the establishment of new interactions between pre-existing
      proteins, we rebuilt putative orthologous ISPs in 17 eukaryotic organisms. Then,
      we computed the conservation of orthologous ISPs at different levels, from
      sequence similarity of orthologous proteins to co-evolution of interacting
      domains. We found that the emergence of glucostatic role in mammals can neither
      be explained by the development of new sets of signaling elements, nor by the
      establishment of new interactions between pre-existing proteins. The comparison
      of orthologous IRS molecules indicates that only in mammals have they acquired
      their complete functionality as efficient recruiters of effector sub-pathways.

PMID- 18616979
TI  - Nonlinear transient computation as a potential "kernel trick" in cortical
      processing.
AB  - Evidence has been found for the presence of chaotic dynamics at all levels of the
      mammalian brain. This has led to some searching questions about the potential
      role that nonlinear dynamics may have in neural information processing. We
      propose that chaos equips the brain with the equivalent of a kernel trick for
      solving hard nonlinear problems. The approach presented, which is described as
      nonlinear transient computation, uses the dynamics of a well known chaotic
      attractor. The paper provides experimental results to show that this approach can
      be used to solve some challenging pattern recognition tasks. The paper also
      offers evidence to suggest that the efficacy of nonlinear transient computation
      for nonlinear pattern classification is dependent only on the generic properties
      of chaotic attractors and is not sensitive to the particular dynamics of specific
      sub-regions of chaotic phase space. If, as this work suggests, nonlinear
      transient computation is independent of the particulars of any given chaotic
      attractor, then it could be offered as a possible explanation of how the chaotic
      dynamics that have been observed in brain structures contribute to neural
      information processing tasks.

PMID- 18616980
TI  - A cell pattern generation model based on an extended artificial regulatory
      network.
AB  - Cell pattern generation has a fundamental role in both artificial and natural
      development. This paper presents results from a model in which a genetic
      algorithm (GA) was used to evolve an artificial regulatory network (ARN) to
      produce predefined 2D cell patterns through the selective activation and
      inhibition of genes. The ARN used in this work is an extension of a model
      previously used to create simple geometrical patterns. The GA worked by evolving
      the gene regulatory network that was used to control cell reproduction, which
      took place in a testbed based on cellular automata (CA). After the final
      chromosomes were produced, a single cell in the middle of the CA lattice was
      allowed to replicate controlled by the ARN found by the GA, until the desired
      cell pattern was formed. The model was applied to the problem of generating a
      French flag pattern.

PMID- 18616981
TI  - Event-driven simulation of cerebellar granule cells.
AB  - Around half of the neurons of a human brain are granule cells (approximately
      10(11)granule neurons) [Kandel, E.R., Schwartz, J.H., Jessell, T.M., 2000.
      Principles of Neural Science. McGraw-Hill Professional Publishing, New York]. In
      order to study in detail the functional role of the intrinsic features of this
      cell we have developed a pre-compiled behavioural model based on the simplified
      granule-cell model of Bezzi et al. [Bezzi, M., Nieus, T., Arleo, A., D'Angelo,
      E., Coenen, O.J.-M.D., 2004. Information transfer at the mossy fiber-granule cell
      synapse of the cerebellum. 34th Annual Meeting. Society for Neuroscience, San
      Diego, CA, USA]. We can use an efficient event-driven simulation scheme based on
      lookup tables (EDLUT) [Ros, E., Carrillo, R.R., Ortigosa, E.M., Barbour, B., Ags,
      R., 2006. Event-driven simulation scheme for spiking neural networks using lookup
      tables to characterize neuronal dynamics. Neural Computation 18 (12), 2959-2993].
      For this purpose it is necessary to compile into tables the data obtained through
      a massive numerical calculation of the simplified cell model. This allows network
      simulations requiring minimal numerical calculation. There are three major
      features that are considered functionally relevant in the simplified granule cell
      model: bursting, subthreshold oscillations and resonance. In this work we
      describe how the cell model is compiled into tables keeping these key properties
      of the neuron model.

PMID- 18616982
TI  - Perspective: from molecular endocrinology of mouse to genomic endocrinology of
      animals.
AB  - This short perspective explores some ways in which new genomic methodologies
      impact the study of endocrine signaling. Emphasis is put on the impact of
      studying species which are not molecular biology models. This opens the door to
      using knowledge molecular endocrinology in areas of biology as distant as
      conservation biology, as well as enriching endocrinology with information from
      biodiversity and natural variation.

PMID- 18616983
TI  - Branched-chain amino acids and arginine suppress MaFbx/atrogin-1 mRNA expression
      via mTOR pathway in C2C12 cell line.
AB  - The effect of amino acid on muscle protein degradation remains unclear. Recent
      studies have elucidated that proteolysis in catabolic conditions occurs through
      ubiquitin-proteasome proteolysis pathway and that muscle-specific ubiquitin
      ligases (atrogin-1 and MuRF1) play an important role in protein degradation. In
      the present study, we examined the direct effect of 5 mM amino acids (leucine,
      isoleucine, valine, glutamine and arginine) on atrogin-1 and MuRF1 levels in
      C2C12 muscle cells and the involved intracellular signal transduction pathway.
      Leucine, isoleucine and valine suppressed atrogin-1 and MuRF1 mRNA levels
      (approximately equal to 50%) at 6 and 24 h stimulations. Arginine showed a
      similar effect except at 24 h-treatment for atrogin-1 mRNA. However, glutamine
      failed to reduce atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of
      leucine, isoleucine or arginine on atrogin-1 mRNA level was reversed by
      rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89
      reduced basal atrogin-1 level without influencing the inhibitory effects of those
      amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1
      mRNA levels was not reversed by rapamycin. Taken together, these findings
      indicated that leucine, isoleucine and arginine decreased atrogin-1 mRNA levels
      via mTOR and that different pathways were involved in the effect of those amino
      acids on MuRF1 mRNA levels.

PMID- 18616984
TI  - Influences of entopeduncular nucleus stimulation upon electromyogram activity of
      masticatory muscles.
AB  - Influences of stimulation of the entopeduncular nucleus (Ep) upon electromyogram
      (EMG) activity of masticatory muscles were examined. In the rat lightly
      anesthetized with halothane, high frequency (HF) microstimulation (trains of 20,
      333-Hz cathodal pulses at 30-60 microA) and GABA microinjection (0.2-0.6 microl
      of 10 mM GABA dissolved in physiological saline) were performed in the Ep by
      using a three-barreled microelectrode. EMG activity was recorded from the
      anterior digastrics and the anterior superficial masseter muscles by using two
      fine enamel-insulated copper wires. The EMG activity was also evoked by the GABA
      microinjection. The effect of the GABA microinjection was negated by the
      microinjection of bicuculline prior to the GABA microinjection. The EMG activity
      was classified into the tonic spike-type, burst-type, or mixed type on the basis
      of the waveform. In each rat, the location of the microelectrode tip was
      estimated by observing a series of serial frontal sections through the whole
      rostrocaudal extent of the Ep. The present data suggested that Ep neurons
      involved in elicitation of tonic spike-type activity in the jaw muscles might be
      located mainly in the rostral third of the Ep, and that Ep neurons implicated in
      provocation of burst-type activity in jaw muscles might be located in the caudal
      third of the Ep. Possible neuronal pathways from the Ep to motoneurons
      innervating the masticatory muscles were discussed. The present data shed new
      light on the control mechanisms of the basal ganglia upon jaw movements.

PMID- 18616985
TI  - Exposure to an open-field arena increases c-Fos expression in a distributed
      anxiety-related system projecting to the basolateral amygdaloid complex.
AB  - Anxiety states and anxiety-related behaviors appear to be regulated by a
      distributed and highly interconnected system of brain structures including the
      basolateral amygdala. Our previous studies demonstrate that exposure of rats to
      an open-field in high- and low-light conditions results in a marked increase in c
      Fos expression in the anterior part of the basolateral amygdaloid nucleus (BLA)
      compared with controls. The neural mechanisms underlying the anatomically
      specific effects of open-field exposure on c-Fos expression in the BLA are not
      clear, however, it is likely that this reflects activation of specific afferent
      input to this region of the amygdala. In order to identify candidate brain
      regions mediating anxiety-induced activation of the basolateral amygdaloid
      complex in rats, we used cholera toxin B subunit (CTb) as a retrograde tracer to
      identify neurons with direct afferent projections to this region in combination
      with c-Fos immunostaining to identify cells responding to exposure to an open
      field arena in low-light (8-13 lux) conditions (an anxiogenic stimulus in rats).
      Adult male Wistar rats received a unilateral microinjection of 4% CTb in
      phosphate-buffered saline into the basolateral amygdaloid complex. Rats were
      housed individually for 11 days after CTb injections and handled (HA) for 2 min
      each day. On the test day rats were either, 1) exposed to an open-field in low
      light conditions (8-13 lux) for 15 min (OF); 2) briefly HA or 3) left undisturbed
      (control). We report that dual immunohistochemical staining for c-Fos and CTb
      revealed an increase in the percentage of c-Fos-immunopositive basolateral
      amygdaloid complex-projecting neurons in open-field-exposed rats compared with HA
      and control rats in the ipsilateral CA1 region of the ventral hippocampus,
      subiculum and lateral entorhinal cortex. These data are consistent with the
      hypothesis that exposure to the open-field arena activates an anxiety-related
      neuronal system with convergent input to the basolateral amygdaloid complex.

PMID- 18616986
TI  - Involvement of cyclooxygenase-2 in lipopolysaccharide-induced impairment of the
      newborn cell survival in the adult mouse dentate gyrus.
AB  - There is growing evidence indicating that neurogenesis in adulthood is influenced
      by certain types of the central diseases such as neuroinflammation, however, its
      mechanism is not fully understood. This study was, therefore, designed to examine
      the effects of lipopolysaccharide (LPS), a bacterial endotoxin known to cause the
      neuroinflammation, on the neurogenesis in the dentate gyrus of adult mice using
      the bromodeoxyuridine (BrdU) -pulse chase method. LPS failed to affect the number
      of BrdU-labeled cells in the dentate gyrus 2 h after BrdU injection, indicating
      no effects of LPS on the proliferation of the neural stem cells (NSCs). On the
      other hand, we found that LPS dose-dependently (0.1, 0.5, 1 mg/kg) decreased the
      number of BrdU-labeled cells 7 and 21 days after BrdU injection. We also observed
      that LPS increased cell death in the dentate gyrus using terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining,
      suggesting that LPS impaired the survival of newborn cells derived from the NSCs.
      The double-immunostaining for BrdU and specific cell type markers revealed that
      LPS did not alter the commitment of the NSCs to the neurons and astrocytes. The
      systemic injection of indomethacin, a non-selective cyclooxygenase (COX)
      inhibitor, and NS398, a selective COX-2 inhibitor, but not SC560, a selective COX
      1 inhibitor, did not only ameliorate LPS-induced suppression of the newborn cell
      survival, they fully protected against the LPS effect. Furthermore, the central
      injection of NS398 also ameliorated LPS-induced suppression of the newborn cell
      survival in the dentate gyrus. The treatment with LPS increased the expression of
      COX-2 protein 7 h and 7 days after the injection in the dentate gyrus. These
      results suggest that LPS impairs the survival of newly generated cells derived
      from the NSCs in the dentate gyrus without affecting the differentiation fate,
      and these effects of LPS were mediated presumably by COX-2 expression in the
      dentate gyrus.

PMID- 18616987
TI  - Immunostaining of rat brain, spinal cord, sensory neurons and skeletal muscle for
      calcium channel alpha2-delta (alpha2-delta) type 1 protein.
AB  - Alpha2-delta (alpha2-delta) is a membrane-spanning auxiliary protein subunit of
      voltage-gated calcium channels found in muscle and brain. Of the four subtypes of
      alpha2-delta, only alpha2-delta types 1 and 2 (alpha2-delta-1 and alpha2-delta-2)
      bind the drugs gabapentin (Neurontin) and pregabalin (Lyrica). Although recent
      findings indicate that drug binding to alpha2-delta-1 is required for
      pharmacology of pregabalin and gabapentin, previous work has not addressed the
      location of alpha2-delta-1 protein within nervous tissues. A monoclonal antibody
      to alpha2-delta-1 revealed intense immunostaining in certain areas of rat brain,
      spinal cord, dorsal root ganglia, and skeletal muscle, with weaker staining in
      heart muscle, gut and liver. Little immunostaining was seen in spleen, kidney,
      thymus and lung. Staining was dense in some regions of the CNS including spinal
      dorsal horn, anterior olfactory nucleus, anterior amygdala, basolateral (ventral)
      amygdala and cortical amygdala, and the piriform, perirhinal, insular and
      entorhinal cortices. In hippocampus, staining was heterogeneous with greater
      density in areas of glutamate terminals (mossy fiber endings on CA3 pyramidal
      cells and perforant path endings on granule cells and CA1 stratum radiatum).
      Moderate staining occurred in the lateral posterior nucleus of the thalamus,
      superficial layers of neocortex, periaqueductal gray, substantia nigra, stria
      terminalis, nucleus accumbens shell and tegmental nucleus. We propose that areas
      of dense alpha2-delta-1 staining in brain and spinal cord are likely sites of
      action for the analgesic, anticonvulsant and anxiolytic-like actions of
      pregabalin and gabapentin in animal models.

PMID- 18616988
TI  - Hypoxic/ischemic conditions induce expression of the putative pro-death gene
      Clca1 via activation of extrasynaptic N-methyl-D-aspartate receptors.
AB  - The stimulation of extrasynaptic N-methyl-D-aspartate (NMDA) receptors triggers
      cell death pathways and has been suggested to play a key role in cell
      degeneration and neuron loss associated with glutamate-induced excitotoxicity. In
      contrast, synaptic NMDA receptors promote neuronal survival. One mechanism
      through which extrasynaptic NMDA receptors damage neurons may involve Clca1,
      which encodes a putative calcium-activated chloride channel. Here we show that
      Clca1 expression is induced in cultured rat hippocampal neurons exposed to
      oxygen/glucose-free media; this induction is mediated by a signaling pathway
      activated by extrasynaptic NMDA receptors. Clca1 mRNA levels also increased in
      the gerbil hippocampus following a transient forebrain ischemia caused by
      bilateral carotid occlusion. Microelectrode array recordings revealed that oxygen
      glucose deprivation enhances hippocampal network firing rates, which induces c
      fos transcription through a signaling pathway that, in contrast to Clca1, is
      activated by synaptic but not extrasynaptic NMDA receptors. Thus, conditions of
      low oxygen/glucose lead to the activation of both extrasynaptic and synaptic NMDA
      receptors that regulate distinct target genes. Clca1 may be part of the genomic
      death program triggered by extrasynaptic NMDA receptors; it could be a marker for
      ischemic brain damage and a possible target for therapeutic interventions.

PMID- 18616991
TI  - Using protein binding site prediction to improve protein docking.
AB  - Predicting protein interaction interfaces and protein complexes are two important
      related problems. For interface prediction, there are a number of tools, such as
      PPI-Pred, PPISP, PINUP, Promate, and SPPIDER, which predict enzyme-inhibitor
      interfaces with success rates of 23% to 55% and other interfaces with 10% to 28%
      on a benchmark dataset of 62 complexes. Here, we develop, metaPPI, a meta server
      for interface prediction. It significantly improves prediction success rates to
      70% for enzyme-inhibitor and 44% for other interfaces. As shown with Promate,
      predicted interfaces can be used to improve protein docking. Here, we follow this
      idea using the meta server instead of individual predictions. We confirm that
      filtering with predicted interfaces significantly improves candidate generation
      in rigid-body docking based on shape complementarity. Finally, we show that the
      initial ranking of candidate solutions in rigid-body docking can be further
      improved for the class of enzyme-inhibitor complexes by a geometrical scoring
      which rewards deep pockets. A web server of metaPPI is available at scoppi.tu
      dresden.de/metappi. The source code of our docking algorithm BDOCK is also
      available at www.biotec.tu-dresden.de /approximately bhuang/bdock.

PMID- 18616990
TI  - Bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) enhances neurogenesis via
      phosphatidylinositol 3-kinase/Akt and extracellular signal regulated kinase
      activation in the hippocampal subgranular zone after mouse focal cerebral
      ischemia.
AB  - Although neurogenesis in the hippocampus is critical for improvement of
      depressive behaviors and cognitive functions in neurodegeneration disorders,
      there is no therapeutic agent available to promote neurogenesis in adult brain
      following brain ischemic injury. Here we found that i.p. administration of bis(1
      oxy-2-pyridinethiolato)oxovanadium(IV) [VO(OPT)], which stimulates
      phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal regulated
      kinase (ERK) pathways, markedly enhanced brain ischemia-induced neurogenesis in
      the subgranular zone (SGZ) of the mouse hippocampus. VO(OPT) treatment enhanced
      not only the number of proliferating cells but also migration of neuroblasts.
      VO(OPT)-induced neurogenesis was associated with Akt and ERK activation in neural
      precursors in the SGZ. Likewise, VO(OPT)-induced neurogenesis was blocked by both
      PI3K/Akt and mitogen-activated protein kinase/extracellular signal regulated
      kinase kinase (MEK)/ERK inhibitors. VO(OPT) treatment rescued decreased
      phosphorylation of glycogen synthesis kinase 3beta (GSK-3beta) at Ser-9. Finally,
      amelioration of cognitive dysfunction seen following brain ischemia was
      positively correlated with VO(OPT)-induced neurogenesis. Taken together, VO(OPT)
      is a potential therapeutic agent that enhances ischemia-induced neurogenesis
      through PI3K/Akt and ERK activation, thereby improving memory and cognitive
      deficits following brain ischemia.

PMID- 18616989
TI  - Effects of dorsal striatal infusions of R(-)-propylnorapomorphine on kappa-opioid
      mediated locomotor activity in the young rat: possible role of the indirect
      pathway.
AB  - Stimulation of kappa-opioid receptors in the substantia nigra pars reticulata
      (SNPR) increases the locomotor activity of young rats: an effect blocked by
      systemic administration of a D2-like receptor agonist. Based on these initial
      findings, we proposed that: (a) D2-like receptors in the dorsal striatum are
      responsible for attenuating kappa-opioid-induced locomotor activity, and (b) the
      effects of D2-like receptor stimulation are mediated by the indirect pathway,
      which extends from the dorsal striatum to the SNPR via the globus pallidus (GP)
      and subthalamic nucleus (STN). To test the first hypothesis, young rats were
      given a systemic injection (i.p.) of saline or the kappa-opioid receptor agonist
      (+/-)-trans-U50,488 methanesulfonate salt (U50,488) on postnatal day (PD) 18.
      Later in the testing session, rats received bilateral infusions of vehicle or the
      D2-like receptor agonist R(-)-propylnorapomorphine (NPA) into the dorsal
      striatum, and the ability of NPA to block U50,488-induced locomotor activity was
      determined. To test the second hypothesis, rats were given sham or bilateral
      electrolytic lesions of the GP or STN on PD 16. Two days later, saline- and
      U50,488-induced locomotor activity was measured after systemic (i.p.)
      administration of vehicle or NPA. As predicted, dorsal striatal infusions of NPA
      attenuated the U50,488-induced locomotor activity of young rats. Contrary to our
      expectations, bilateral lesions of the GP or STN did not impair NPA's ability to
      block U50,488-induced locomotor activity. When considered together, these results
      suggest that: (a) stimulation of D2-like receptors in the dorsal striatum is
      sufficient to attenuate the kappa-opioid-mediated locomotor activity of young
      rats; and (b) the indirect pathway does not mediate the effects of D2-like
      receptor stimulation in this behavioral model.

PMID- 18616992
TI  - Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto
      reductase (AKR) 1C3.
AB  - Resistance towards anticancer drugs is a general problem upon chemotherapy. Among
      the mechanisms of resistance, metabolic inactivation by carbonyl reduction is a
      major cause of chemotherapy failure that applies to drugs bearing a carbonyl
      moiety. Oracin is a promising anticancer drug which is presently in phase II
      clinical trials. Pharmacokinetic studies have revealed that oracin undergoes
      metabolic inactivation by carbonyl reduction. In the present study, we provide
      evidence that AKR1C3, a member of the aldo-keto reductase (AKR) superfamily,
      catalyzes the inactivation of oracin. Moreover, AKR1C3 does also mediate C13
      carbonyl reduction of doxorubicin to its inactive hydroxy metabolite
      doxorubicinol. Doxorubicinol, however, has also been considered responsible for
      the cardiomyopathy observed upon doxorubicin chemotherapy. Since AKR1C3 is
      overexpressed in hormone-dependent malignancies like prostate and breast cancer,
      coadministration of AKR1C3 inhibitors might enhance the chemotherapeutic efficacy
      of oracin and doxorubicin, and simultaneously reduce the risk of cardiomyopathy
      upon doxorubicin treatment.

PMID- 18616993
TI  - Frontiers of auditory prosthesis research: implications for clinical practice.

PMID- 18616995
TI  - Ascochyta blight of chickpea: production of phytotoxins and disease management.
AB  - Ascochyta blight caused by Ascochyta rabiei (Pass.) Lab., is the most devastating
      disease of chickpea and can occur anywhere the crop is grown. Several epidemics
      of blight causing complete yield losses have been reported. Despite extensive
      pathological and molecular studies, the nature and extent of pathogenic
      variability in A. rabiei have not been clearly established. Several isolates of
      A. rabiei were grown in liquid culture medium which secreted phytotoxic compounds
      of solanapyrone A, B, C and cytochalasin D. The same fungal metabolites were also
      recovered from extract of naturally blight stricken chickpea plants. Toxicity of
      purified solanapyrones as determined by cell bioassay was in the order of
      solanapyrone A>solanapyrone B>solanapyrone C. However, the specificity of all
      three compounds was dependent on the genetic identity of the chickpea cultivars.
      Seed treatment and foliar application of fungicides are commonly recommended for
      disease management, but further information on biology and survival of A. rabiei
      is needed to devise more effective management strategies. A short description of
      chickpea blight, geographical distribution, disease cycle, symptoms, losses,
      production of phytotoxins and disease management practices for the control of
      Ascochyta blight will be discussed in this review article.

PMID- 18616994
TI  - Cochlear implants: a remarkable past and a brilliant future.
AB  - The aims of this paper are to (i) provide a brief history of cochlear implants;
      (ii) present a status report on the current state of implant engineering and the
      levels of speech understanding enabled by that engineering; (iii) describe
      limitations of current signal processing strategies; and (iv) suggest new
      directions for research. With current technology the "average" implant patient,
      when listening to predictable conversations in quiet, is able to communicate with
      relative ease. However, in an environment typical of a workplace the average
      patient has a great deal of difficulty. Patients who are "above average" in terms
      of speech understanding, can achieve 100% correct scores on the most difficult
      tests of speech understanding in quiet but also have significant difficulty when
      signals are presented in noise. The major factors in these outcomes appear to be
      (i) a loss of low-frequency, fine structure information possibly due to the
      envelope extraction algorithms common to cochlear implant signal processing; (ii)
      a limitation in the number of effective channels of stimulation due to overlap in
      electric fields from electrodes; and (iii) central processing deficits,
      especially for patients with poor speech understanding. Two recent developments,
      bilateral implants and combined electric and acoustic stimulation, have promise
      to remediate some of the difficulties experienced by patients in noise and to
      reinstate low-frequency fine structure information. If other possibilities are
      realized, e.g., electrodes that emit drugs to inhibit cell death following trauma
      and to induce the growth of neurites toward electrodes, then the future is very
      bright indeed.

PMID- 18616996
TI  - Identification of phylogenetically conserved enhancer elements implicated in
      pancreas development in the WISP1 and CTGF orthologs.
AB  - WISP1 and CTGF are members of the CCN family of growth factors encoding
      extracellular matrix proteins participating in several developmental and
      tumorigenic processes. Both are induced by the WNT signaling pathway, and
      microarray data suggest that expression of WISP1 and CTGF is repressed by
      Neurogenin3 (Ngn3 (NEUROG3)), a transcription factor directing specification of
      the endocrine pancreas. Single-cell reverse transcription polymerase chain
      reaction analysis suggested that this was a cell autonomous effect. To identify
      possible common regulatory networks involved in WISP1 and CTGF gene expression,
      their genomic regions were searched for common transcription factor motifs using
      a combination of in silico approaches and documented knowledge concerning
      pancreas development. This analysis revealed the presence of a conserved enhancer
      in both CTGF and WISP1 regulatory regions in 10 species covering a wide
      evolutionary distance. This enhancer contains binding sites for Ngn1/3
      (NEUROG1/3) and transcription factors that are critically involved in pancreas
      development. Furthermore, it contained binding sites for three additional
      transcription factor families, which may indicate novel players are involved in
      this process.

PMID- 18616997
TI  - Exercise stress increases susceptibility to influenza infection.
AB  - Exercise stress is associated with an increased risk for upper respiratory tract
      infection (URTI) while moderate exercise has been associated with a decreased
      risk. We have shown that exercise stress can increase susceptibility (morbidity,
      symptom severity and mortality) to HSV-1 respiratory infection, but there is
      little evidence on the effects of stressful exercise on susceptibility to the
      principal etiological agents of human respiratory infections, including influenza
      viruses. This study examined the effects of stressful exercise on susceptibility
      to influenza virus (A/Puerto Rico/8/34 (H1N1)). Mice were assigned to one of two
      groups: exercise (Ex) or control (Con). Exercise consisted of a treadmill run to
      volitional fatigue ( approximately 120 min) performed on three consecutive days.
      Fifteen minutes after the last bout of exercise or rest, mice (n=20-21/group)
      were intranasally inoculated with a standardized dose of influenza virus (0.25
      HAU). Mice were monitored daily for morbidity (time to sickness), symptom
      severity and mortality (time to death) for 21 days. Exercise stress was
      associated with an increase in susceptibility to infection (morbidity, mortality
      and symptom severity on days 6 and 7; P<0.05). These data from a controlled
      influenza virus challenge model add significantly to the growing body of evidence
      that severe exercise can increase susceptibility to URTI.

PMID- 18616971
TI  - Invertebrate muscles: thin and thick filament structure; molecular basis of
      contraction and its regulation, catch and asynchronous muscle.
AB  - This is the second in a series of canonical reviews on invertebrate muscle. We
      cover here thin and thick filament structure, the molecular basis of force
      generation and its regulation, and two special properties of some invertebrate
      muscle, catch and asynchronous muscle. Invertebrate thin filaments resemble
      vertebrate thin filaments, although helix structure and tropomyosin arrangement
      show small differences. Invertebrate thick filaments, alternatively, are very
      different from vertebrate striated thick filaments and show great variation
      within invertebrates. Part of this diversity stems from variation in paramyosin
      content, which is greatly increased in very large diameter invertebrate thick
      filaments. Other of it arises from relatively small changes in filament backbone
      structure, which results in filaments with grossly similar myosin head placements
      (rotating crowns of heads every 14.5 nm) but large changes in detail (distances
      between heads in azimuthal registration varying from three to thousands of
      crowns). The lever arm basis of force generation is common to both vertebrates
      and invertebrates, and in some invertebrates this process is understood on the
      near atomic level. Invertebrate actomyosin is both thin (tropomyosin:troponin)
      and thick (primarily via direct Ca(++) binding to myosin) filament regulated, and
      most invertebrate muscles are dually regulated. These mechanisms are well
      understood on the molecular level, but the behavioral utility of dual regulation
      is less so. The phosphorylation state of the thick filament associated giant
      protein, twitchin, has been recently shown to be the molecular basis of catch.
      The molecular basis of the stretch activation underlying asynchronous muscle
      activity, however, remains unresolved.

PMID- 18616998
TI  - Serotonin-mediated protein carbonylation in the right heart.
AB  - Pulmonary hypertension is a devastating disease, which leads to right heart
      failure. Serotonin (5-HT) plays important roles in the pathogenesis of pulmonary
      hypertension and pulmonary vascular remodeling. The role of 5-HT in right heart
      failure, however, is unknown. Since oxidative stress may mediate heart failure,
      the present study examined the effects of 5-HT on protein oxidation in the adult
      rat right heart ventricle. Treatment of perfused isolated hearts with 5-HT
      resulted in the promotion of protein carbonylation, specifically in the right
      ventricle, but not in the left. While no differences between right and left
      ventricular antioxidant enzymes and 5-HT receptors/transporter were detected,
      monoamine oxidase A (MAO-A) expression and activity were found to be lower in the
      right ventricle compared to the left. These results indicate that differences in
      neither the reactive oxygen species (ROS) scavenging ability, 5-HT membrane
      signaling capacity, nor MAO-dependent production of hydrogen peroxide are
      responsible for varied 5-HT-mediated protein carbonylation in right and left
      ventricles. Rather, lower MAO-A in the right heart might preserve cytosolic 5-HT
      which triggers other mechanisms for ROS production. Consistently, inhibition of
      MAO-A resulted in the promotion of protein carbonylation. We propose that low MAO
      A, thus reduced degradation of 5-HT, increases the intracellular 5-HT activity in
      the right ventricle, leading to the promotion of protein carbonylation.

PMID- 18616999
TI  - Oxidative stresses induced by glycoxidized human or bovine serum albumin on human
      monocytes.
AB  - Oxidative stress and protein modifications are frequently observed in numerous
      disease states. Albumin, the major circulating protein in blood, can undergo
      increased glycoxidation in diabetes. Protein glycoxidation can lead to the
      formation of advanced glycoxidation end products, which induce various
      deleterious effects on cells. Herein, we report the effect of glucose or
      methylglyoxal-induced oxidative modifications on BSA or HSA protein structures
      and on THP1 monocyte physiology. The occurrence of oxidative modifications was
      found to be enhanced in glycoxidized BSA and HSA, after determination of their
      free thiol group content, relative electrophoretic migration, carbonyl content,
      and antioxidant activities. Cells treated with glycoxidized albumin exhibited an
      overgeneration of intracellular reactive oxygen species, impairments in
      proteasomal activities, enhancements in RAGE expression, and an accumulation of
      carbonylated proteins. These novel observations made in the presence of a range
      of modified BSA and HSA facilitate the comparison of the glycoxidation extent of
      albumin with the oxidative stress induced in cultured monocytes. Finally, this
      study reconfirms the influence of experimental conditions in which AGEs are
      generated and the concentration levels in experiments designed to mimic
      pathological conditions.

PMID- 18617000
TI  - Both EGFR kinase and Src-related tyrosine kinases regulate human ether-a-go-go
      related gene potassium channels.
AB  - Human ether-a-go-go-related gene (hERG or Kv11.1) encodes the rapidly activated
      delayed rectifier K(+) current (I(Kr)) in the human heart. Potential regulation
      of hERG channel by protein tyrosine kinases (PTKs) is not understood. The present
      study was designed to investigate whether this channel is modulated by PTKs using
      whole-cell patch clamp technique, and immunoprecipitation and Western blot
      analysis in HEK 293 cells stably expressing hERG gene. We found that the broad
      spectrum PTK inhibitor genistein (30 microM), the selective EGFR (epidermal
      growth factor receptor) kinase inhibitor AG556 (10 microM) and the Src-family
      kinase inhibitor PP2 (10 microM) remarkably inhibited hERG channel current
      (I(hERG)), and the effects were significantly countered by the protein tyrosine
      phosphatase (PTP) inhibitor orthovanadate (1 mM). Immunoprecipitation and Western
      blot analysis demonstrated that membrane protein tyrosine phosphorylation of hERG
      channels was reduced by genistein, AG556, and PP2. The reduction of hERG channel
      phosphorylation level by genistein, AG556 or PP2 was antagonized by
      orthovanadate. Single point mutation(s) of Y475A and/or Y611A dramatically
      attenuated the inhibitory effect of I(hERG) by PP2 and/or AG556. Our results
      demonstrate the novel information that I(hERG) is modulated not only by Src
      family kinases, but also by EGFR kinases. Y475 and/or Y611 are likely the
      preferred phosphorylation sites. Regulation of hERG channels by PTKs modifies the
      channel activity and thus likely alters electrophysiological properties including
      action potential duration and cell excitability in human heart and neurons.

PMID- 18617001
TI  - Cell lineage in mammalian craniofacial mesenchyme.
AB  - We have analysed the contributions of neural crest and mesoderm to mammalian
      craniofacial mesenchyme and its derivatives by cell lineage tracing experiments
      in mouse embryos, using the permanent genetic markers Wnt1-cre for neural crest
      and Mesp1-cre for mesoderm, combined with the Rosa26 reporter. At the end of
      neural crest cell migration (E9.5) the two patterns are reciprocal, with a mutual
      boundary just posterior to the eye. Mesodermal cells expressing endothelial
      markers (angioblasts) are found not to respect this boundary; they are associated
      with the migrating neural crest from the 5-somite stage, and by E9.5 they form a
      pre-endothelial meshwork throughout the cranial mesenchyme. Mesodermal cells of
      the myogenic lineage also migrate with neural crest cells, as the branchial
      arches form. By E17.5 the neural crest-mesoderm boundary in the subectodermal
      mesenchyme becomes out of register with that of the underlying skeletogenic
      layer, which is between the frontal and parietal bones. At E13.5 the primordia of
      these bones lie basolateral to the brain, extending towards the vertex of the
      skull during the following 4-5 days. We used DiI labelling of the bone primordia
      in ex-utero E13.5 embryos to distinguish between two possibilities for the origin
      of the frontal and parietal bones: (1) recruitment from adjacent connective
      tissue or (2) proliferation of the original primordia. The results clearly
      demonstrated that the bone primordia extend vertically by intrinsic growth,
      without detectable recruitment of adjacent mesenchymal cells.

PMID- 18617002
TI  - Determination of factors controlling the particle size in nanoemulsions using
      Artificial Neural Networks.
AB  - The purpose of this study was to use Artificial Neural Networks (ANNs) in
      identifying factors, in addition to surfactant and internal phase content, that
      influence the particle size of nanoemulsions. The phase diagram and rheometric
      characteristics of a nanoemulsion system containing polysorbate 80, ethanol,
      medium chain triglycerides and normal saline loaded with budesonide were
      investigated. The particle size of samples of various compositions prepared using
      different rates and amounts of applied energy was measured. Data, divided into
      training, test and validation sets, were modelled by ANNs. The developed model
      was assessed and found to be of high quality. The model was then used to explore
      the effect of composition and processing factors on particle size of the
      nanoemulsion preparation. The study demonstrates the potential of ANNs in
      identifying critical parameters controlling preparation for this system, with the
      total amount of applied energy during preparation found to be the dominant factor
      in controlling the final particle size.

PMID- 18617003
TI  - Fluorescently tagged laminin subunits facilitate analyses of the properties,
      assembly and processing of laminins in live and fixed lung epithelial cells and
      keratinocytes.
AB  - Recent analyses of collagen, elastin and fibronectin matrix assembly,
      organization and remodeling have been facilitated by the use of tagged proteins
      that can be visualized without the need for antibody labeling. Here, we report
      the generation of C-terminal tagged, full-length and "processed" (alpha3DeltaLG4
      5) human alpha3 as well as C-terminal tagged, full-length human beta3 laminin
      subunits in adenoviral vectors. Human epidermal keratinocytes (HEKs) and human
      bronchial epithelial (BEP2D) cells, which assemble laminin-332-rich matrices, as
      well as primary rat lung alveolar type II (ATII) cells, which elaborate a fibrous
      network rich in laminin-311, were infected with adenovirus encoding the tagged
      human laminin subunits. In HEKs and BEP2D cells, tagged, full-length alpha3,
      alpha3DeltaLG4-5 and beta3 laminin subunits incorporate into arrays of matrix
      organized into patterns that are comparable to those observed when such cells are
      stained using laminin-332 subunit antibody probes. Moreover, HEKs and BEP2Ds move
      over these tagged, laminin-332-rich matrix arrays. We have also used the tagged
      beta3 laminin subunit-containing matrices to demonstrate that assembled laminin
      332 arrays influence laminin matrix secretion and/or assembly. In the case of rat
      ATII cells, although tagged alpha3 laminin subunits are not detected in the
      matrix of rat ATII cells infected with virus encoding full-length human alpha3
      laminin protein, processed human alpha3 laminin subunits are incorporated into an
      extracellular fibrous array. We discuss how these novel laminin reagents can be
      used to study the organization, processing and assembly of laminin matrices and
      how they provide new insights into the potential functional importance of laminin
      fragments.

PMID- 18617004
TI  - Standardizing experimental protocols.
AB  - Systems biology aims at understanding the behavior of biological networks by
      mathematical modeling based on experimental data. However, frequently
      experimental data is derived from poorly defined cellular systems, the procedures
      of data generation are insufficiently documented and data processing is
      arbitrary. For the advancement of systems biology, standardization at multiple
      levels is essential. Several systems biology consortia have started by focusing
      on standardization of cellular systems and experimental procedures. Minimum
      information standards for the description of data sets and common languages for
      the description of biological pathways as well as for mathematical modeling are
      being developed. Standardization is required to facilitate data exchange between
      different research groups and finally the assembly of large integrated models
      providing novel biological insights.

PMID- 18617005
TI  - Quilty in biopsy is associated with poor prognosis after heart transplantation.
AB  - We tested if Quilty (endocardial infiltration of lymphocytes) in routinely
      processed endomyocardial biopsy is associated with poor outcome after heart
      transplantation (HTx). Biopsies (n=9829) harvested within the first post
      transplant year from 938 patients (778 men, mean age 49 years) were evaluated for
      Quilty and acute cellular rejection (according to the International Society for
      Heart and Lung Transplantation, ISHLT, classification). Transplant vasculopathy
      was evaluated by coronary angiography, and severe stenosis was found in 19% of
      patients. Survival was tested by Kaplan-Meier and Cox regression analyses for all
      cause mortality and major cardiac events (lethal acute cellular rejection, graft
      loss or myocardial infarction). We found 1840 (19%) Quilty-positive biopsies in
      487 Quilty-positive patients (52%). Quilty was more prevalent in women (p=0.038)
      and younger men (p=0.001), and was correlated with ISHLT grade 1R (OR 1.45, 95%
      CI 1.36-1.55; p<0.001) and ISHLT grade 2R (OR 2.48, 95% CI 2.21-3.41; p<0.001).
      Quilty in any biopsy was associated with a higher all-cause mortality (log rank
      p=0.045) due to a higher risk for major cardiac event (p=0.0001). Multivariate
      regression analysis showed Quilty (RR 1.69, 95%CI 1.05-2.73) and transplant
      vasculopathy (RR 2.78, 95%CI 1.68-4.61) as risk factors for major cardiac events
      and treated hyperlipidemia as lowering the risk for major cardiac events (RR
      0.47, 95%CI 0.28-0.77). Quilty is associated with graft loss and poor outcome
      post HTx. Index biopsy during the first post-transplant year is a useful tool to
      identify patients at risk and is recommended during routine post-transplant
      management.

PMID- 18617006
TI  - Oxidative stress in normal and impaired wound repair.
AB  - A large percentage of the population suffers from wound healing abnormalities, in
      particular aged individuals, patients with diabetes, and those treated with
      immunosuppressive drugs, chemo- or radiotherapy. The mechanisms underlying the
      impaired healing response are still poorly understood. Recent studies provided
      strong evidence for a role of oxidative stress in the pathogenesis of non-healing
      ulcers. Therefore, it is of major importance to identify and functionally
      characterize the factors involved in the generation and detoxification of
      reactive oxygen species (ROS). This will provide the basis for the development of
      new strategies for therapeutic intervention. In this review we summarize the
      current information about the roles of low molecular weight antioxidants and ROS
      detoxifying enzymes in normal and impaired wound repair, and we report on the
      consequences of their modulation at the wound site.

PMID- 18617008
TI  - Cadherin-6 gene regulatory patterns in the postnatal mouse brain.
AB  - Cadherin-6 (Cdh6, K-cadherin) is a synaptic adhesion molecule the expression of
      which demarcates restricted sets of neuronal circuitries in postnatal mouse
      brains. While roles for the cadherins in the formation and/or modulation of
      synaptic junctions have been implicated, that which drives cadherin expression
      along functional brain circuits has remained elusive. Here we investigate the
      genetic control of Cdh6 expression by applying a method that permits systematic
      integration of a reporter cassette into bacterial artificial chromosomes with
      extensive coverage of the huge Cdh6 gene locus, whereby the reporter activities
      are efficiently evaluated in stable transgenic mouse lines. Such screenings
      revealed that divisible genomic segments differentially control each brain region
      or nucleus specific expression of Cdh6 at the right phases for circuit formation.
      These separable regulatory modules for cadherin expressions tended to be grouped
      by working connectivities, suggesting their developmental and/or evolutional
      value in elaborating brain circuitry.

PMID- 18617007
TI  - Blocking connexin43 expression reduces inflammation and improves functional
      recovery after spinal cord injury.
AB  - After traumatic CNS injury, a cascade of secondary events expands the initial
      lesion. The gap-junction protein connexin43 (Cx43), which is transiently up
      regulated, has been implicated in the spread of 'bystander' damage. We have used
      an antisense oligodeoxynucleotide (asODN) to suppress Cx43 up-regulation in two
      rat models of spinal cord injury. Within 24 h of compression injury, rats treated
      with Cx43-asODN scored higher than sense-ODN and vehicle-treated controls on
      behavioural tests of locomotion. Their spinal cords showed less swelling and
      tissue disruption, less up-regulation of astrocytic GFAP, and less extravasation
      of fluorescently-labelled bovine serum albumin and neutrophils. The locomotor
      improvement was sustained over at least 4 weeks. Following partial spinal cord
      transection, Cx43-asODN treatment reduced GFAP immunoreactivity, neutrophil
      recruitment, and the activity of OX42(+) microglia in and around the lesion site.
      Cx43 has many potential roles in the pathophysiology of CNS injury and may be a
      valuable target for therapeutic intervention.

PMID- 18617009
TI  - Sensorimotor tongue representation in individuals with unilateral upper limb
      amelia.
AB  - The purpose of the present study was to examine the impact of the congenital
      absence of one hand on cortical organization of the sensorimotor cortex (S1/M1).
      We investigated the tongue representation in S1/M1 in nine participants with
      normally developed limbs, comprising the control group, and in eight persons with
      a congenitally completely missing hand (i.e. unilateral hand amelia). All
      participants were examined by fMRI while performing horizontal tongue movements.
      The significantly activated clusters covering S1/M1 in both hemispheres were
      analyzed with respect to the number and intensity of activated voxels, as well as
      the location of the activation. In the right-handed control group, the number of
      activated voxels was significantly higher in the left as compared to the right
      hemisphere demonstrating a clear left hemispheric motor dominance for horizontal
      tongue movements. In the amelic individuals, no such hemispheric lateralization
      effect was observed. The neural activation pattern underlying tongue movement,
      however, was enlarged and displaced in the hemisphere contralateral to the
      missing limb when compared to the respective motor non-dominant, right hemisphere
      of the control group participants. The present findings suggest that congenital
      absence of one hand leads to an appreciably altered topological organization of
      S1/M1 consisting of an enlargement of the tongue representation and a shift
      towards the "hand" area which, however, had never received any input from a hand.

PMID- 18617010
TI  - Replication potentials of vif variant viruses generated from monkey cell-tropic
      HIV-1 derivative clones NL-DT5/NL-DT5R.
AB  - To obtain monkey-tropic viruses that are more closely related to HIV-1 than the
      original NL-DT5/NL-DT5R clones, we constructed six vif-chimeric and two site
      specific vif-mutant viruses, and examined their growth ability. Different from NL
      DT5/NL-DT5R, these viruses did not grow in monkey cells. We monitored the
      capability of the mutants to antagonize monkey APOBEC3G/F by single-cycle
      infectivity assays. They counteracted poorly or not at all the action of the
      APOBEC3G/F. Our results have indicated that the native SIVmac Vif is required to
      overcome the species barrier against HIV-1.

PMID- 18617011
TI  - Targeted imaging: an important biomarker for understanding disease progression in
      the era of personalized medicine.
AB  - The key to applying targeted imaging to personalized medicine is the choice of
      the right radiolabeled probe for the right target for the right disease following
      the lead of pharmaceutical development. The imaging approach differs depending on
      whether the target is a single disease control point (e.g. a specific receptor or
      transport protein linked to the mechanistic activity of a drug) or a general
      disease control point applicable to a number of treatment paradigms (e.g.
      proliferation, angiogenesis, inflammation). But in either case, the number of
      control points must be small given the time constraints on molecular imaging
      procedures in the clinic. Regardless of the choice, the radiotracer must be
      validated as binding to the target with the appropriate pharmacokinetics and
      pharmacodynamics for effective external imaging. Such an imaging agent developed
      in concert with drug development has a built in synergy that will accelerate the
      drug development process, targeted imaging and personalized medicine as well.

PMID- 18617012
TI  - New challenges for pharmaceutical formulations and drug delivery systems
      characterization using isothermal titration calorimetry.
AB  - Long viewed as the 'method of choice' for characterizing thermodynamics and
      stoichiometry of molecular interactions, with high sensitivity, isothermal
      titration calorimetry (ITC) has been applied to many areas of pharmaceutical
      analysis. This review highlights ITC employment to measure binding thermodynamics
      and their use for pharmaceutical formulations and drug delivery system
      characterization particularly cyclodextrin-guest interactions, investigation of
      micellar-based systems, polyelectrolytes, nucleic acid interactions with
      multivalent cations and the optimization of DNA targeting and delivery.
      Furthermore, the potential of ITC for the characterization of different
      functionalities carried by nanoparticles as well as their interaction with living
      systems was outlined.

PMID- 18617013
TI  - The array CGH and its clinical applications.
AB  - Array comparative genomic hybridization (aCGH) is a technique enabling high
      resolution, genome-wide screening of segmental genomic copy number variations
      (CNVs). It is becoming an essential and a routine clinical diagnostic tool and is
      gradually replacing cytogenetic methods. Most of the clinically available aCGH
      platforms are designed to detect aneuploidies, well-characterized
      microdeletion/microduplication syndromes and subtelomeric or other unbalanced
      chromosomal rearrangements. In addition, aCGH can uncover numerous CNVs of
      unclear significance scattered throughout the human genome. But this technology
      is not able to identify balanced chromosomal imbalances such as translocations
      and inversions and some ploidies. aCGH increased the ability to detect segmental
      genomic CNVs in patients with global developmental delay, mental retardation,
      autism, multiple congenital anomalies and dysmorphism, and is becoming a powerful
      tool in disease gene discovery and prenatal diagnostics. This tool is also
      showing promising data in cancer research and in the diagnosis, classification
      and prognostication of different malignancies.

PMID- 18617014
TI  - Cardiotoxicity of the new cancer therapeutics--mechanisms of, and approaches to,
      the problem.
AB  - Cardiotoxicity of some targeted therapeutics, including monoclonal antibodies and
      small-molecule inhibitors, is a reality. Herein we will examine why it occurs,
      focusing on molecular mechanisms to better understand the issue. We will also
      examine how big the problem is and, more importantly, how big it may become in
      the future. We will review models for detecting cardiotoxicity in the preclinical
      phase. We will also focus on two key areas that drive cardiotoxicity:
      multitargeting and the inherent lack of selectivity of ATP-competitive
      antagonists. Finally, we will examine the issue of reversibility and discuss
      possible approaches to keeping patients on therapy.

PMID- 18617015
TI  - Limitations and lessons in the use of X-ray structural information in drug
      design.

PMID- 18617016
TI  - Male pattern baldness: current treatments, future prospects.
AB  - Male pattern baldness affects up to half of the male Caucasian population by
      middle age, and almost all Caucasian men by old age. Especially in younger men,
      this heritable form of hair loss can have significant psycho-social consequences.
      Although approved pharmacological agents exist to manage the condition, none of
      the currently available options are highly efficacious. New treatments under
      development, and acceleration in our understanding of the underlying molecular
      genetic aetiology of this condition provide increased hope for future targeted
      treatment strategies.

PMID- 18617017
TI  - Addressing informatics challenges in Translational Research with workflow
      technology.
AB  - Interest in Translational Research has been growing rapidly in recent years. In
      this collision of different data, technologies and cultures lie tremendous
      opportunities for the advancement of science and business for organisations that
      are able to integrate, analyse and deliver this information effectively to users.
      Workflow-based integration and analysis systems are becoming recognised as a fast
      and flexible way to build applications that are tailored to scientific areas, yet
      are built on a common platform. Workflow systems are allowing organisations to
      meet the key informatics challenges in Translational Research and improve disease
      understanding and patient care.

PMID- 18617018
TI  - Patient-perceived risk associated with epilepsy and its medication treatment.
AB  - Regardless of the expert advice of health care practitioners, it is ultimately
      the patient's decision how to best manage his or her condition. This decision can
      be influenced by the perceived risk of both the disease and its treatment. The
      objective of this study was to develop a survey to evaluate perceived risk
      associated with epilepsy and its medication treatment. Risk was evaluated in five
      domains: performance, financial, social, psychological, and physical. A 40-item
      patient-perceived risk questionnaire was developed and administered to patients
      at one university-affiliated epilepsy clinic. Pearson correlation and regression
      analysis was used to identify significant components of overall perceived risk. A
      total of 64 patients completed the survey. Performance and physical risk
      significantly explained 34% of the variance in overall perceived risk associated
      with epilepsy. The overall perceived risk associated with the treatment of
      epilepsy was explained by performance, physical, psychological, and social risks
      (r(2)=0.386). Thus, the treatment of epilepsy poses more challenges for patients
      to maintain their lifestyle than the disease itself.

PMID- 18617019
TI  - Expression of Robo/Slit and Semaphorin/Plexin/Neuropilin family members in the
      developing hypothalamic paraventricular and supraoptic nuclei.
AB  - The hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON)
      contain neuroendocrine cells that modulate pituitary secretion to maintain
      homeostasis. These two nuclei have a common developmental origin but they
      eventually form at locations distant from each other. Little is known about the
      molecular cues that direct the segregation of PVN and SON. As a means to identify
      potential factors, we have documented expression patterns of genes with known
      guidance roles in neural migration. Here, we focus on two groups of
      ligand/receptor families classified to mediate chemo-repulsion of neurons and
      their axons: the Slit/Robo and the Semaphorin/Plexin/Neuropilin families. Their
      dynamic expression patterns within and around the common PVN/SON progenitor as
      well as the mature PVN and SON may provide a framework for understanding the
      formation of these two important nuclei.

PMID- 18617020
TI  - Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in
      the host.
AB  - Methylglyoxal is a normal metabolite and has the potential to affect a wide
      variety of cellular processes. In particular, it can act selectively against
      malignant cells. The study described herein was to investigate whether
      methylglyoxal can enhance the non-specific immunity of the host against tumor
      cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity
      of both normal and tumor-bearing mice. It also elevated the phagocytic capacity
      of macrophages in both these groups of animals. This activation of macrophages
      was brought about by increased production of Reactive Oxygen Intermediates (ROIs)
      and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the
      production of ROIs and RNIs can be attributed to stimulation of the respiratory
      burst enzyme NADPH oxidase and iNOS, respectively. IFN-gamma, which is a
      regulatory molecule of iNOS pathway also showed an elevated level by
      methylglyoxal. TNF-alpha, which is an important cytokine for oxygen independent
      killing by macrophage also increased by methylglyoxal in both tumor-bearing and
      non tumor-bearing animals. Methylglyoxal also played a role in the proliferation
      and cytotoxicity of splenic lymphocytes. In short, it can be concluded that
      methylglyoxal profoundly stimulates the immune system against tumor cells.

PMID- 18617021
TI  - Predictive value of antinuclear autoantibodies: the lessons of the systemic
      sclerosis autoantibodies.
AB  - Physicians who provide care to patients with systemic sclerosis (SSc,
      scleroderma) ask themselves several questions: Is SSc the correct diagnosis? Can
      the disease course be predicted? Is there a greater risk for involvement of
      certain organs? Can the vital prognosis be predicted? In this brief review, we
      answer these questions by excerpting data from the literature focused on the 4
      major SSc specific autoantibodies (aAbs) to nuclear autoantigens (ANAs): anti
      centromere (anti-CENP-B), anti-Th/To, anti-topoisomerase I (anti-topo I) and anti
      RNA polymerase III (anti-RNAPIII). The data show that these aAbs are highly
      valuable as markers for the diagnosis of SSc, as biomarkers for phenotypic
      subsets and as prognostic markers. We also identify areas for future clinical
      research.

PMID- 18617022
TI  - The stability and aggregation properties of the GTPase domain from human SEPT4.
AB  - The septins are a family of conserved proteins involved in cytokinesis and
      cortical organization. An increasing amount of data implicates different septins
      in diverse pathological conditions including neurodegenerative disorders,
      neoplasia and infections. Human SEPT4 is a member of this family and its tissue
      specific ectopic expression profile in colorectal and urologic cancer makes it a
      useful diagnostic biomarker. Thermal unfolding of the GTPase domain of SEPT4
      (SEPT4-G) revealed an unfolding intermediate which rapidly aggregates into
      amyloid-like fibers under physiological conditions. In this study, we examined
      the effects of protein concentration, pH and metals ions on the aggregation
      process of recombinant SEPT4-G using a series of biophysical techniques, which
      were also employed to study chemical unfolding and stability. Divalent metal ions
      caused significant acceleration to the rate of SEPT4-G aggregation. Urea induced
      unfolding was shown to proceed via the formation of a partially unfolded
      intermediate state which unfolds further at higher urea concentrations. The
      intermediate is a compact dimer which is unable to bind GTP. At 1 M urea
      concentration, the intermediate state was plagued by irreversible aggregation at
      temperatures above 30 degrees C. However, higher urea concentration resulted in a
      marked decay of the aggregation, indicating that the partially folded structures
      may be necessary for the formation of these aggregates. The results presented
      here are consistent with the recently determined crystal structure of human
      septins and shed light on the aggregation properties of SEPT4 pertinent to its
      involvement in neurodegenerative disease.

PMID- 18617023
TI  - Parallel and integrative processing through the Basal Ganglia reward circuit:
      lessons from addiction.

PMID- 18617024
TI  - Rankings.

PMID- 18617025
TI  - High pressure freezing and freeze substitution of Schizosaccharomyces pombe and
      Saccharomyces cerevisiae for TEM.
AB  - The use of standard room temperature chemical fixation protocols for the
      ultrastructural preservation of yeast and subsequent observation under the
      electron microscope is fraught with difficulties. Many protocols require the use
      of enzymatic digestion of the cell wall in order to facilitate the entry of
      fixatives into the cell interior. Others rely on the use of permanganate-based
      fixative solutions, which whilst enabling overall preservation of the cell, does
      require multiple centrifugation, washing, and resuspension steps. This often
      results in the significant loss of sample volume whilst the use of permanganate
      can cause extraction of cytoplasmic components. The use of low temperature
      techniques and in particular high pressure freezing (HPF) and freeze substitution
      (FS) overcomes many of these problems. With the recent advances in
      cryotechnologies and in particular the development of commercially available
      equipment such as the high pressure freezer, the level of ultrastructural
      preservation attainable in electron microscopy has increased markedly. It is now
      possible to capture dynamic time sensitive events and to place them in their
      ultrastructural context with a level of resolution which at the present time can
      only be achieved with electron microscopy.

PMID- 18617026
TI  - Electron probe X-ray microanalysis for the study of cell physiology.
AB  - Of the analytical electron microscopy techniques available, electron probe X-ray
      microanalysis has been most widely used for the study of biological specimens.
      This technique is able to identify, localize, and quantify elements both at the
      whole cell and at the intracellular level. The use SEM or TEM to analyze
      individual whole cells gives a simple and rapid method to study changes in ion
      transport after stimulation, whereas the analysis of thin sections of
      cryoprepared cell sections, although technically more difficult, allows details
      about ionic content in intracellular compartments, such as mitochondria, ER, and
      lysosomes, to be obtained. In this chapter the principles underlying X-ray
      emission are briefly outlined, step-by-step methods for specimen preparation of
      whole cells and cell sections for microanalysis are given, as are the methods
      used for deriving quantitative information from spectra. Areas where problems
      might occur have been highlighted. The different areas in which X-ray
      microanalysis is being used in the study of cell physiology are briefly reviewed.

PMID- 18617027
TI  - Preparation of cells and tissues for immuno EM.
AB  - Transmission electron microscopy (TEM) provides a powerful set of methods to
      investigate cellular and subcellular structures using thin sections. In this
      article we summarize some of the different approaches available for researchers
      interested in using these methods. The essential details involved in specimen
      preparation for immunolabelling are covered. The best sectioning approach for
      preserving specimens for structural analysis is Cryo EM of Vitrified Sections
      (CEMOVIS), a method where still frozen sections are examined in the transmission
      electron microscope. Because the specimens are kept at low temperature during
      sectioning and examination, this method is not amenable for immunolabelling,
      where antibodies are applied to sections at ambient temperature. To combine
      structural analysis with immunocytochemical analysis of antigens, the approach of
      freeze-substitution without chemical fixative is the method of choice, at least
      from a theoretical point of view. In practice, however, the vast majority of
      electron microscopic (EM) immunocytochemical analyses are carried out using
      chemically-fixed specimens that have been embedded in specialized resins (such as
      the Lowicryls) using freeze-substitution or ambient temperature methods. Antibody
      labelling of thawed cryosections through chemically-fixed specimens (the Tokuyasu
      method) is also a popular method for preparing cells and tissues for TEM
      analysis. Here, we provide an overview of all these sectioning methods for EM,
      focusing mostly on the practical details. Given the space limitation, the fine
      details necessary to apply these methods have been successfully omitted and will
      have to be obtained from the technical references we provide.

PMID- 18617028
TI  - Quantification of structures and gold labeling in transmission electron
      microscopy.

PMID- 18617029
TI  - Combined video fluorescence and 3D electron microscopy.
AB  - Three-dimensional structure of cells and organelles examined with the power of
      resolution of electron microscopy (EM) including EM tomography represents the
      average view of cell processes. More precise and detailed analysis is limited by
      the significant variations in the structure of cells in temporal dynamics of
      cellular events. Therefore EM cannot identify rare and fast events that could be
      extremely important for understanding molecular mechanisms underlying these
      cellular processes. Observation of living cells under EM is still impossible. In
      contrast, observations of cellular dynamics with the help of laser scanning
      confocal microscopes or light digitalized microscopes became an indispensable
      tool of cell biology. However, the resolution of even confocal microscope is
      limited to the half of the light wave. Therefore, in studies of dynamic cellular
      processes, it would be ideal to be able to combine the capability of in vivo
      fluorescence video microscopy with the EM. This chapter describes this technique
      with details and useful tricks, including the way to localize the same cell after
      its transfection with a protein fused with a fluorescent tag, examination under
      the microscope in living condition, fixation, immunolabeling, embedding, serial
      sectioning from the first section, and observation under EM. We also illustrate
      here the kinds of questions that the CVLEM approach was designed to address, as
      well as the particular know-how that is important for the successful application
      of this technique.

PMID- 18617030
TI  - From live-cell imaging to scanning electron microscopy (SEM): the use of green
      fluorescent protein (GFP) as a common label.
AB  - The identification and characterization of many biological substructures at high
      resolution requires the use of electron microscopy (EM) technologies. Scanning
      electron microscopy (SEM) allows the resolution of cellular structures to
      approximately 3 nm and has facilitated the direct visualization of macromolecular
      structures, such as nuclear pore complexes (NPCs), which are essential for nucleo
      cytoplasmic molecular trafficking. However, SEM generates only static images of
      fixed samples and therefore cannot give unambiguous information about protein
      dynamics. The investigation of active processes and analysis of protein dynamics
      has greatly benefited from the development of molecular biology techniques
      whereby vectors can be generated and transfected into tissue culture cells for
      the expression of specific proteins tagged with a fluorescent moiety for real
      time light microscopy visualization. As light microscopy is limited in its powers
      of resolution relative to electron microscopy, it has been important to adapt a
      protocol for the processing of samples for real-time imaging by conventional
      light microscopy with protein labels that can also be identified by SEM. This
      allows correlation of dynamic events with high resolution molecular and
      structural identification. This method describes the use of GFP for tracking the
      dynamic distribution of NPC components in real-time throughout the cell cycle and
      for high resolution immuno-SEM labeling to determine localization at the
      nanometer level.

PMID- 18617031
TI  - Immunolabeling for scanning electron microscopy (SEM) and field emission SEM.
AB  - Scanning electron microscopy (SEM) is a high resolution surface imaging
      technique. Many biological process and structures occur at surfaces and if
      antibodies are available, their components can be located within the surface
      structure. This is usually done in a similar way to immuno-fluorescence, using an
      unconjugated primary antibody followed by a tagged secondary antibody against the
      primary. In this case the tag is usually a colloidal gold particle instead of a
      fluorophore. Therefore it is quite straightforward to adapt an immuno
      fluorescence procedure for SEM, as long as certain precautions are followed, as
      discussed here. Progressing from immuno-fluorescence, which essentially only
      indicates the position of a protein within the volume of a cell, to immuno-SEM,
      puts the labeling into the context of cellular structures. The principles and
      practices of sample preparation, labeling and imaging are described here.

PMID- 18617032
TI  - Immunogold labeling of thawed cryosections.

PMID- 18617033
TI  - Close-to-native ultrastructural preservation by high pressure freezing.
AB  - The objective of modern transmission electron microscopy (TEM) in life science is
      to observe biological structures in a state as close as possible to the living
      organism. TEM samples have to be thin and to be examined in vacuum; therefore
      only solid samples can be investigated. The most common and popular way to
      prepare samples for TEM is to subject them to chemical fixation, staining,
      dehydration, and embedding in a resin (all of these steps introduce considerable
      artifacts) before investigation. An alternative is to immobilize samples by
      cooling. High pressure freezing is so far the only approach to vitrify (water
      solidification without ice crystal formation) bulk biological samples of about
      200 micrometer thick. This method leads to an improved ultrastructural
      preservation. After high pressure freezing, samples have to be subjected to
      follow-up procedure, such as freeze-substitution and embedding. The samples can
      also be sectioned into frozen hydrated sections and analyzed in a cryo-TEM. Also
      for immunocytochemistry, high pressure freezing is a good and practicable way.

PMID- 18617034
TI  - High-pressure freezing and low-temperature fixation of cell monolayers grown on
      sapphire coverslips.

PMID- 18617035
TI  - Freeze-fracture cytochemistry in cell biology.
AB  - The term freeze-fracture cytochemistry embraces a series of techniques which
      share the goal of chemical identification of the structural components viewed in
      freeze-fracture replicas. As one of the major features of freeze fracture is its
      ability to provide planar views of membranes, a major emphasis in freeze-fracture
      cytochemistry is to identify integral membrane proteins, study their spatial
      organization in the membrane plane, and examine their role in dynamic cellular
      processes. Effective techniques in freeze-fracture cytochemistry, of wide
      application in cell biology, are now available. These include fracture-label,
      label fracture, and the freeze-fracture replica immunolabeling technique (FRIL).
      In fracture-label, samples are frozen and fractured, thawed for labeling, and
      finally processed for viewing either by critical-point drying and platinum-carbon
      replication or by thin-section electron microscopy. Label-fracture involves
      immunogold labeling a cell suspension, processing as for standard freeze-fracture
      replication, and then examining the replica without removal of the cellular
      components. Of greatest versatility, however, is the FRIL technique, in which
      samples are frozen, fractured, and replicated with platinum-carbon as in standard
      freeze fracture, and then carefully treated with sodium dodecylsulphate (SDS) to
      remove all the biological material except a fine layer of molecules attached to
      the replica itself. Immunogold labeling of these molecules permits the
      distribution of identified components to be viewed superimposed upon high
      resolution planar views of replicated membrane structure, for both the plasma
      membrane and intracellular membranes in cells and tissues. Examples of how these
      techniques have contributed to our understanding of cardiovascular cell function
      in health and disease are discussed.

PMID- 18617036
TI  - Three-dimensional molecular architecture of the plasma-membrane-associated
      cytoskeleton as reconstructed by freeze-etch electron tomography.

PMID- 18617038
TI  - Correlated light and electron microscopy of the cytoskeleton.
AB  - The cytoskeleton of cultured cells can be most easily visualized in the electron
      microscope by simultaneous extraction and fixation with Triton-glutaraldehyde
      mixtures, followed by negative staining. Actin filaments are better preserved by
      stabilization with phalloidin, either during or after the primary fixation step.
      A technique is described for the combination of this procedure with live cell
      microscopy. Optimal conditions for light microscopy are achieved by culturing
      cells on coverslips coated with formvar film. For cell relocation a gold finder
      grid pattern is embossed on the film by evaporation through a tailor-made mask.
      After video microscopy and fixation, the film is floated from the coverslip and
      an electron microscope grid added to the film with the central hole of the grid
      over the region of interest. Accurate positioning is achieved under a dissecting
      microscope, using forceps mounted in a micromanipulator. Examples are shown of
      the changes in organization of actin filaments in the lamellipodia of migrating
      melanoma cells resulting from changes in protrusion rate. The technique is
      applicable to alternative processing procedures after fixation, including
      cryoelectron tomography.

PMID- 18617037
TI  - Visualization of dynamins.

PMID- 18617039
TI  - Electron microscopy of intermediate filaments: teaming up with atomic force and
      confocal laser scanning microscopy.
AB  - Intermediate filaments (IFs) were originally discovered and defined by electron
      microscopy in myoblasts. In the following it was demonstrated and confirmed that
      they constitute, in addition to microtubules and microfilaments, a third
      independent, general filament system in the cytoplasm of most metazoan cells. In
      contrast to the other two systems, IFs are present in cells in two principally
      distinct cytoskeletal forms: (i) extended and free-running filament arrays in the
      cytoplasm that are integrated into the cytoskeleton by associated proteins of the
      plakin type; and (ii) a membrane- and chromatin-bound thin 'lamina' of a more or
      less regular network of interconnected filaments made from nuclear IF proteins,
      the lamins, which differ in several important structural aspects from cytoplasmic
      IF proteins. In man, more than 65 genes code for distinct IF proteins that are
      expressed during embryogenesis in various routes of differentiation in a tightly
      controlled manner. IF proteins exhibit rather limited sequence identity implying
      that the different types of IFs have distinct biochemical properties. Hence, to
      characterize the structural properties of the various IFs, in vitro assembly
      regimes have been developed in combination with different visualization methods
      such as transmission electron microscopy of fixed and negatively stained samples
      as well as methods that do not use staining such as scanning transmission
      electron microscopy (STEM) and cryoelectron microscopy as well as atomic force
      microscopy. Moreover, with the generation of both IF-type specific antibodies and
      chimeras of fluorescent proteins and IF proteins, it has become possible to
      investigate the subcellular organization of IFs by correlative fluorescence and
      electron microscopic methods. The combination of these powerful methods should
      help to further develop our understanding of nuclear architecture, in particular
      how nuclear subcompartments are organized and in which way lamins are involved.

PMID- 18617040
TI  - Studying microtubules by electron microscopy.
AB  - Microtubules are one of the three components of the eukaryotic cytoskeleton and
      play a central role in many aspects of cell function, including cell division and
      cell motility. Electron microscopy, of both isolated microtubules and of
      microtubules in their cellular context, is an essential tool in understanding
      their structure and function. These studies have been particularly important
      because the size and heterogeneity of microtubules mean that they are not readily
      studied by other structural methods. Electron microscopy at different levels of
      detail can bridge the gap between atomic resolution structures solved by X-ray
      crystallography or NMR, and the dynamic but relatively coarse information that is
      achieved in light microscopy experiments. This chapter provides an overview of
      current approaches to studying microtubules by electron microscopy. Negative
      stain studies can be relatively quick and easy, and provide a useful overview of
      microtubules and their interactions prior to undertaking more complicated
      experiments such as high resolution structure determination by cryo-electron
      microscopy or reconstruction of unique cellular entities by electron tomography.
      As more microtubule-associated proteins are uncovered, EM studies will make a
      significant contribution to our understanding of how these proteins influence
      microtubules and where in the cytoskeleton they act.

PMID- 18617041
TI  - Electron microscopy of collagen fibril structure in vitro and in vivo including
      three-dimensional reconstruction.
AB  - Tissue development in multicellular animals relies on the ability of cells to
      synthesize an extracellular matrix (ECM) containing spatially organized collagen
      fibrils, whose length greatly exceeds that of individual cells. The importance of
      the correct regulation of fibril deposition is exemplified in diseases such as
      osteogenesis imperfecta (caused by mutations in collagen genes), fibrosis (caused
      by ectopic accumulation of collagen), and cardiovascular disease (which involves
      cells and macromolecules binding to collagen in the vessel wall). Much is known
      about the molecular biology of collagens but less is known about collagen fibril
      structure and how the fibrils are formed (fibrillogenesis). This is explained in
      part by the fact that the fibrils are noncrystalline, extensively cross-linked,
      and very large, which makes them refractory to study by conventional biochemical
      and high-resolution structure-determination techniques. Electron microscopy has
      become established as the method of choice for studying collagen fibril structure
      and assembly. This article describes the electron microscopic methods most often
      used in studying collagen fibril assembly and structure.

PMID- 18617042
TI  - Visualization of desmosomes in the electron microscope.
AB  - Desmosomes are intercellular junctions found in epithelia and some other tissues.
      Their primary function is strong cell-cell adhesion. They also link the
      intermediate filament (IF) cytoskeletons between cells and have roles in cell
      signaling, tissue morphogenesis, and wound repair. Because of their size (0.2-0.5
      microm), details of their ultrastructure can only be resolved at the electron
      microscope (EM) level. Desmosomes have been visualized using a variety of
      ultrastructural techniques including lanthanum infiltration, freeze-fracture,
      electron tomography, cryo-electron microscopy and immunogold labeling. This
      chapter describes protocols for conventional transmission electron microscopy and
      for immunogold labeling of ultrathin cryosections. We also discuss the
      statistical analysis of immunogold particle distribution for low resolution
      molecular mapping.

PMID- 18617043
TI  - A protocol for isolation and visualization of yeast nuclei by scanning electron
      microscopy.
AB  - This article describes a protocol that details methods for the isolation of yeast
      nuclei from budding yeast (Saccharomyces cerevisiae) and fission yeast
      (Schizosaccharomyces pombe), immunogold labelling of proteins, and visualization
      by Field Emission Scanning Electron Microscopy (FESEM). This involves the removal
      of the yeast cell wall and isolation of the nucleus from within, followed by
      subsequent processing for high resolution microscopy. The nuclear isolation step
      is performed by enzymatic treatment of yeast cells to rupture the cell wall and
      generate spheroplasts (cells that have partially lost their cell wall and their
      characteristic shape), followed by isolation of nuclei by centrifugation. This
      protocol has been optimized for the visualization of the yeast nuclear envelope
      (NE), nuclear pore complexes (NPCs), and associated cytoskeletal structures.
      Samples, once processed for FESEM, can be stored under vacuum for weeks, allowing
      considerable time for image acquisition.

PMID- 18617044
TI  - Scanning electron microscopy of nuclear structure.
AB  - Accessing internal structure and retaining relative three dimensional (3D)
      organization within the nucleus has always proved difficult in the electron
      microscope. This is due to the overall size and largely fibrous nature of the
      contents, making large scale 3D reconstructions difficult from thin sections
      using transmission electron microscopy. This chapter brings together a number of
      methods developed for visualization of nuclear structure by scanning electron
      microscopy (SEM). These methods utilize the easily accessed high resolution
      available in field emission instruments. Surface imaging has proved particularly
      useful to date in studies of the nuclear envelope and pore complexes, and has
      also shown promise for internal nuclear organization, including the dynamic and
      radical reorganization of structure during cell division. Consequently, surface
      imaging in the SEM has the potential to make a significant contribution to our
      understanding of nuclear structure.

PMID- 18617045
TI  - Electron microscopy of lamin and the nuclear lamina in Caenorhabditis elegans.
AB  - The nuclear lamina is found between the inner nuclear membrane and the peripheral
      chromatin. Lamins are the main components of the nuclear lamina, where they form
      protein complexes with integral proteins of the inner nuclear membrane,
      transcriptional regulators, histones and chromatin modifiers. Lamins are required
      for mechanical stability, chromatin organization, Pol II transcription, DNA
      replication, nuclear assembly, and nuclear positioning. Mutations in human lamins
      cause at least 13 distinct human diseases, collectively termed laminopathies,
      affecting muscle, adipose, bone, nerve and skin cells, and range from muscular
      dystrophies to accelerated aging. Caenorhabditis elegans has unique advantages in
      studying lamins and nuclear lamina genes including low complexity of lamina genes
      and the unique ability of bacterially expressed C. elegans lamin protein to form
      stable 10 nm fibers. In addition, transgenic techniques, simple application of
      RNA interference, sophisticated genetic analyses, and the production of a large
      collection of mutant lines, all make C. elegans especially attractive for
      studying the functions of its nuclear lamina genes. In this chapter we will
      include a short review of our current knowledge of nuclear lamina in C. elegans
      and will describe electron microscopy techniques used for their analyses.

PMID- 18617046
TI  - Visualization of nuclear organization by ultrastructural cytochemistry.

PMID- 18617047
TI  - Scanning electron microscopy of chromosomes.
AB  - Scanning electron microscopic analysis is an indispensable tool for high
      resolution visualization of chromosomes and their ultrastructural details. It
      allows a three-dimensional structural approach for elucidating higher-order
      chromatin structure and chromosome architecture. Artificial decondensation under
      a variety of conditions shows that structural elements of chromosomes are
      composed of matrix fibers and chromomeres. Currently, chromosome labeling methods
      include DNA contrasting with platinum blue, silver contrasting of proteins, and
      immunolabeling with Nanogold. With these techniques, DNA and protein distribution
      can be determined, and functionally relevant elements (e.g., epigenetic
      modifications, specific proteins, DNA sequences) can be located to structural
      elements of chromosomes with, at present, local resolution of approximately 30
      nm.

PMID- 18617048
TI  - Infection at the cellular level.
AB  - Fine structural analysis of the infection process is indispensable for
      understanding the relation between microorganisms and host cells. This chapter
      focuses on standard techniques for transmission as well as scanning electron
      microscopy that will be of benefit even to researchers new to the field.

PMID- 18617049
TI  - Electron microscopy of viruses and virus-cell interactions.
AB  - Electron microscopy is a powerful tool to visualize viruses in diagnostic as well
      as in research settings for investigating viral structure and virus-cell
      interactions. Here, a simple but efficient method is described for demonstrating
      viruses by negative staining, and its limit is discussed. A prerequisite to
      obtain reliable information on virus-cell interactions is excellent preservation
      of cellular and viral ultrastructure. The crux is that during fixation and
      embedding, by applying conventional protocols about 50% of the lipids are lost,
      which results in loss of integrity of cell membranes. To achieve good
      preservation of cellular architectures, good contrast, and both high spatial and
      temporal resolution, methods for freezing, freeze-substitution, and freeze
      etching are described and their applicability discussed mostly taking complicated
      built herpes viruses as examples.

PMID- 18617050
TI  - Stuttering and its treatment in adolescence: the perceptions of people who
      stutter.
AB  - Adolescence is a complicated phase of maturation during which a great deal of
      physical, neurological and social development occurs. Clinically this phase is
      thought to be the last chance to arrest the development of the disorder of
      stuttering before it becomes chronic in adulthood. However, little treatment
      development for this age group has occurred. Previous research on the impact of
      stuttering during adolescence presents a complex picture of apprehension about
      speaking which does not, however, appear to interfere with social life. The
      purpose of the present study was to investigate further the experiences of
      adolescents who stutter with respect to: (1) their experience of stuttering
      during the adolescent years, (2) reasons for seeking or not seeking therapy
      during the adolescent years, (3) barriers to seeking therapy during the
      adolescent years, (4) their experience of therapy during the adolescent years,
      and finally (5) suggested improvements to therapy for adolescents. Two focus
      groups and seven individual interviews were conducted with 13 adolescents and
      young adults. The major finding was a perceived lack of awareness about
      stuttering by teachers and parents, as well as other adolescents. In addition it
      appeared that having a stutter was, in itself, not enough reason to seek
      treatment. However when adolescents did seek treatment, for reasons such as
      joining the workforce, group therapy was well liked. EDUCATIONAL OBJECTIVES: The
      reader will summarize key features that characterize: (1) the complex
      developmental phase of adolescence, (2) evaluate the experience of stuttering
      during the adolescent years, (3) discuss the experience of stuttering therapy
      during the adolescent years, (4) list adolescents' reported barriers to seeking
      therapy during the adolescent years, and (5) suggest possible ways to improve
      management of stuttering in adolescence.

PMID- 18617051
TI  - The effectiveness of SpeechEasy during situations of daily living.
AB  - A multiple single-subject design was used to examine the effects of SpeechEasy on
      stuttering frequency in the laboratory and in longitudinal samples of speech
      produced in situations of daily living (SDL). Seven adults who stutter
      participated, all of whom had exhibited at least 30% reduction in stuttering
      frequency while using SpeechEasy during previous laboratory assessments. For each
      participant, speech samples recorded in the laboratory and SDL during device use
      were compared to samples obtained in those settings without the device. In SDL,
      stuttering frequencies were recorded weekly for 9-16 weeks during face-to-face
      and phone conversations. Participants also provided data regarding device
      tolerance and perceived benefits. Laboratory assessments were conducted at the
      beginning and the end of the longitudinal data collection in SDL. All seven
      participants exhibited reduced stuttering in self-formulated speech in the Device
      compared to No-device condition during the first laboratory assessment. In the
      second laboratory assessment, four participants exhibited less stuttering and
      three exhibited more stuttering with the device than without. In SDL, five of
      seven participants exhibited some instances of reduced stuttering when wearing
      the device and three of these exhibited relatively stable amounts of stuttering
      reduction during long-term use. Five participants reported positive changes in
      speaking-related attitudes and perceptions of stuttering. Further investigation
      into the short- and long-term effectiveness of SpeechEasy in SDL is warranted.
      EDUCATIONAL OBJECTIVES: The reader will be able to summarize: (1) issues
      pertinent to evaluating treatment benefits of wearable fluency aids and evaluate
      (2) the effect of SpeechEasy on stuttering frequency and the perceived benefits
      of device use in situations of daily living, as assessed weekly over the course
      of 9-16 weeks of wear, for seven adults who stutter.

PMID- 18617052
TI  - The effect of SpeechEasy on stuttering frequency, speech rate, and speech
      naturalness.
AB  - The effects of SpeechEasy on stuttering frequency, stuttering severity self
      ratings, speech rate, and speech naturalness for 31 adults who stutter were
      examined. Speech measures were compared for samples obtained with and without the
      device in place in a dispensing setting. Mean stuttering frequencies were reduced
      by 79% and 61% for the device compared to the control conditions on reading and
      monologue tasks, respectively. Mean severity self-ratings decreased by 3.5 points
      for oral reading and 2.7 for monologue on a 9-point scale. Despite dramatic
      reductions in stuttering frequency, mean global speech rates in the device
      condition increased by only 8% in the reading task and 15% for the monologue
      task, and were well below normal. Further, complete elimination of stuttering was
      not associated with normalized speech rates. Nevertheless, mean ratings of speech
      naturalness improved markedly in the device compared to the control condition
      and, at 3.3 and 3.2 for reading and monologue, respectively, were only slightly
      outside the normal range. These results show that SpeechEasy produced improved
      speech outcomes in an assessment setting. However, findings raise the issue of a
      possible contribution of slowed speech rate to the stuttering reduction effect,
      especially given participants' instructions to speak chorally with the delayed
      signal as part of the active listening instructions of the device protocol. Study
      of device effects in situations of daily living over the long term is necessary
      to fully explore its treatment potential, especially with respect to long-term
      stability. EDUCATIONAL OBJECTIVES: The reader will be able to discuss and
      evaluate: (1) issues pertinent to evaluating treatment benefits of fluency aids
      and (2) the effects of SpeechEasy on stuttering frequency, speech rate, and
      speech naturalness during testing in a dispensing setting for a relatively large
      sample of adults who stutter.

PMID- 18617053
TI  - Age of acquisition and repetition priming effects on picture naming of children
      who do and do not stutter.
AB  - The effects of age of acquisition and repetition priming on picture naming
      latencies and errors were studied in 22 children who stutter (CWS) and 22
      children who do not stutter (CWNS) between the ages of 3;1 and 5;7. Children
      participated in a computerized picture naming task where they named pictures of
      both early and late acquired (AoA) words in two consecutive stages. Findings
      revealed that all children's picture naming latencies and errors were reduced
      following repetition priming and in response to early AoA words relative to late
      AoA words. AoA and repetition priming effects were similar for children in both
      talker groups, with one exception. Namely, CWS benefitted significantly more, in
      terms of error reduction, than CWNS from repetition priming for late AoA words.
      In addition, CWNS exhibited a significant, positive association between
      linguistic speed and measures of vocabulary, but CWS did not. These findings were
      taken to suggest that the (a) semantic-phonological connections of CWS may not be
      as strong as those of CWNS, and (b) existing lexical measures may not be
      sensitive enough to differentiate CWS from CWNS in lexically related aspects of
      language production. EDUCATIONAL OBJECTIVES: After reading this article, the
      learner will be able to: (a) describe the effects of repetition priming and age
      of word acquisition in speech production; (b) summarize the performance
      similarities and differences of children who stutter and children who do not
      stutter on a computerized picture naming task; and (c) compare the results of the
      present study with previous work in this area.

PMID- 18617055
TI  - Assessment of 1p/19q deletions by fluorescence in situ hybridization in gliomas.
AB  - This study assessed the efficacy of FISH for detecting 1p/19q deletion in gliomas
      on 77 paraffin-embedded tissue samples, of which 42 cases (55%) were positive for
      1p/19q codeletion; 7 of the 42 had a previous history of glioma. In one case,
      analysis failed. The remaining 34 cases were negative; of these, three had a
      previous history of glioma and one had the reverse 1q/19p deletion. A majority of
      the 10 recurrent gliomas had progressed, and 70% had a 1p/19q deletion. The
      signal pattern in a majority of 1p/19q codeletion cases was a single red marker
      signal and two green reference signals (1R2G) for both probe sets. One case had a
      different signal pattern for chromosomes 1 and 19 (1R2G and 2R4G), as seen in
      polysomy cells. Three cases had two target and four control signals (2R4G), as
      seen in tetraploid cells. Eleven had complex signal patterns seen in diploid and
      polyploid cells (1R2G/<nRnG). A majority of these complex cases (8 of 11, or 73%)
      had high-grade oligodendroglioma (n = 4) or oligoastrocytoma (n = 4). The
      frequency of 1p/19q combined deletion in oligodendroglioma (n = 40),
      oligoastrocytoma (n = 21), and astrocytoma (n = 8) was 65, 60, and 25%,
      respectively. Elucidated in this paper are the various FISH signal patterns
      observed in gliomas and a need for a uniform nomenclature for improved diagnosis.

PMID- 18617056
TI  - Genome-wide genetic characterization of an atypical meningioma by single
      nucleotide polymorphism array-based mapping and classical cytogenetics.
AB  - Most meningiomas, accounting for about 20% of intracranial tumors, can be cured
      by surgical removal. Yet, 8-22% of these tumors are classified as atypical or
      anaplastic (WHO grade II or III, respectively) presenting with a more aggressive
      behavior and a high relapse rate. We analyzed genomic alterations of an atypical
      meningioma using high-density single nucleotide polymorphism arrays (SNP-A)
      karyotyping combined with GTG-banding, multicolor fluorescence in situ
      hybridization (M-FISH), and locus-specific FISH. In accordance to recent studies
      applying SNP-A karyotyping in different malignancies we found that genomic
      lesions are present at a higher frequency than predicted by traditional
      cytogenetics. Most of these aberrations have not been described before.
      Additionally, we unveiled loss of heterozygosity (LOH) without copy number
      changes on chromosome regions 1p31.1, 2p16.1, 2q23.3, 6q14.1, 6q21, 9p21.1,
      10q21.1, and 14q23.3, suggesting partial uniparental disomy (UPD). UPDs are
      currently considered to play an important role in the initiation and progression
      of different malignancies. Furthermore, we detected two de novo reciprocal
      translocations, t(8;19)(q24;q13) and t(10;16)(q22;q12.1). While GTG-banding and M
      FISH data suggested balanced translocations, SNP-A analysis clearly demonstrated
      imbalances in the same region.

PMID- 18617057
TI  - Analysis of gene rearrangements using a fluorescence in situ hybridization method
      in Mexican patients with acute lymphoblastic leukemia: experience at a single
      institution.
AB  - We evaluated the prevalence of BCR/ABL, MLL, and ETV6/RUNX1 rearrangements as
      well as CDKN2A (alias p16) deletion in a group of Mexican children with acute
      lymphoblastic leukemia (ALL) to determine whether the changes coexist, and to
      compare the incidences found with other reports in the literature. To increase
      the detection of these abnormalities, we combined conventional cytogenetics and
      fluorescence in situ hybridization (FISH) analysis. Bone marrow samples were
      obtained from 59 consecutive children with ALL. FISH detected a total of 63
      abnormalities with the selected probes, 34 of which were related to the
      conventional cytogenetic results. The most common abnormality was the p16
      deletion (22.8%), followed by MLL and ETV6/RUNX1 rearrangements (8.7%), and the
      BCR/ABL fusion was the least frequent (2.7%). The coexistence of two recurrent
      abnormalities with specific prognostic significance in the same patient was not
      found. A lesser proportion of the p16 deletion in T-ALL patients was observed,
      probably related to the low prevalence of this subtype in our population. In
      addition, we confirmed the low frequency of the ETV6/RUNX1 fusion observed in
      Hispanics. Due to the different prevalence of these abnormalities in the Mexican
      population, similar studies should be conducted analyzing new rearrangements, to
      improve the adequate classification of the abnormalities and the stratification
      in prognostic groups.

PMID- 18617058
TI  - Monosomy 7 and absence of 12q amplification in two cases of spindle cell
      liposarcomas.
AB  - Spindle cell liposarcoma (SCL) is a rare malignant adipose tissue tumor presently
      regarded as a variant of well-differentiated liposarcoma (WDLPS). While WDLPS is
      cytogenetically characterized by the presence of supernumerary ring or giant
      chromosomes containing MDM2 amplification, data concerning the genomic
      alterations of SCL are scarce. Here, we describe the molecular cytogenetic
      characterization of two SCL cases. In these two cases, we did not identify
      supernumerary ring or giant chromosomes containing 12q amplification or any other
      chromosome 12 rearrangement. Instead, we observed a partial or complete monosomy
      7 as the sole anomaly or among a few additional simple numeric and structural
      abnormalities. Monosomy 7 is not usual in adipose tissue tumors. It has been
      described in myelodysplastic syndromes and acute myeloid or lymphoblastic
      leukemias, as well as in several benign or malignant solid tumors. Our data
      suggest that the loss of material from chromosome 7 might play a crucial role in
      the pathogenesis of some SCL probably through the inactivation of tumor
      suppressor genes located on chromosome 7. On the basis of cytogenetic and
      molecular findings, some SCL may constitute an independent entity rather than
      being regarded as variants of WDLPS.

PMID- 18617059
TI  - Telomere aggregates in non-Hodgkin lymphoma patients at different disease stages.
AB  - Telomeres of tumor nuclei tend to form aggregates (TA). The same phenomenon was
      also observed in premalignant states. The aim of this study was to estimate TA
      formation in leukocytes of patients with non-Hodgkin lymphoma (NHL) at different
      disease stages (diagnosis, treatment, relapse, and remission). The peptide
      nucleic acid Telomere Kit was used to evaluate TA formation, using two
      dimensional fluorescence microscopy. A higher rate of TA was found in all the NHL
      stages (including remission) than in the control group. Significantly higher TA
      formation was also observed in the relapse group, compared to the diagnosis
      group. It may be possible that patients with higher TA numbers are prone to
      relapse. From our previous results involving replication pattern, random
      aneuploidy rate, and (recently) TA formation, it can be concluded that the
      patients in remission are at higher risk of developing relapse than the normal
      population throughout their life span. The genetic instability parameters remain
      in the cells of these patients, who must continue to be monitored throughout
      their life.

PMID- 18617060
TI  - A novel variant form of MLL-ELL fusion transcript with t(11;19)(q23;p13.1) in
      chronic myelomonocytic leukemia transforming to acute myeloid leukemia.
AB  - MLL located at 11q23 is fused with a variety of partner genes by recurrent
      chromosomal translocations in acute leukemias. ELL, the MLL partner gene located
      on chromosome 19p13.1, encodes an RNA polymerase II transcriptional elongation
      factor, which also possesses the N-terminal region involved in the inhibition of
      transcription initiation. Here we report a case of chronic myelomonocytic
      leukemia (CMML) with a 46,XY,t(11;19)(q23;p13.1) karyotype that transformed to
      acute myeloid leukemia (AML) without showing any karyotypic evolution. Interphase
      fluorescent in situ hybridization analysis showed the split MLL signals in 95% of
      bone marrow cells when the diagnosis of CMML was made and the percentage of
      blasts was 1.2%. Sequence analysis of reverse-transcriptional polymerase chain
      reaction product revealed a novel variant form of MLL-ELL transcript in which MLL
      exon 10 was fused to ELL exon 3. MLL has been fused to ELL exon 2 in all the
      previously reported MLL-ELL transcripts, which have always been associated with
      AML. It is deduced that the variant form of MLL-ELL may be defective not only in
      inhibition of transcription initiation, but also in transcriptional elongation.
      Thus, a possibility is raised that the unique clinical presentation of the
      present case with t(11;19)(q23;p13.1) might be related to the variant form of MLL
      ELL.

PMID- 18617061
TI  - Spectral karyotyping and fluorescence in situ hybridization analyses identified a
      novel three-way translocation involving inversion 16 in therapy-related acute
      myeloid leukemia M4eo.
AB  - We report a novel three-way translocation involving inversion 16 and chromosome
      12 at bands 16p13, 16q22, and 12q24 in a patient with therapy-related acute
      myeloid leukemia (AML)-M4eo. Conventional G-banding of bone marrow cells at
      diagnosis was suggestive of inv(16)(p13q22) and a translocation of chromosomes 12
      and 16. The presence of inv(16) was confirmed by reverse-transcription polymerase
      chain reaction (RT-PCR) analysis, which corresponded to the type A CBFB-MYH11
      chimeric transcript. Spectral karyotyping (SKY) analysis clearly identified a
      reciprocal translocation between chromosomes 12 and 16. In addition, dual-color
      fluorescence in situ hybridization (FISH) analysis revealed a fusion signal for
      the CBFB and MYH11 probes and a signal for the MYH11 probe on the der(16)
      chromosome, as well as a signal for the CBFB probe on the der(12) chromosome.
      Thus, the karyotype was refined to
      46,XX,der(12)t(12;16)(q24;q22),der(16)inv(16)(p13q22)t(12;16). Although we could
      not establish that this complex chromosomal aberration occurred either as a one
      step, three-way event, or a sequential event with inv(16)(p13q22) followed by
      t(12;16)(q24;q22), SKY in combination with FISH and RT-PCR analyses successfully
      detected this complex chromosome abnormality in the patient.

PMID- 18617062
TI  - TP53 mutations in synchronous and metachronous bilateral breast carcinomas.

PMID- 18617063
TI  - Association of inv(3)(q21q26) with essential thrombocythemia in transformation.

PMID- 18617064
TI  - Lineage switch from acute myeloid leukemia to biphenotypic acute leukemia with
      acquisition of Philadelphia chromosome.

PMID- 18617065
TI  - Acute myocardial infarction associated with pregnancy.
AB  - Acute myocardial infarction (AMI) during pregnancy or the early post-partum
      period is rare but has been shown to be associated with poor maternal as well as
      fetal outcome. Major changes in both diagnosis and treatment of AMI in the
      nonpregnant patient have lead to improved outcome which may also affect pregnant
      patients. The purpose of this paper is to review available information related to
      the pathophysiology and clinical profile and provide recommendations for the
      diagnosis and management of AMI occuring during pregnancy and the early post
      partum period.

PMID- 18617066
TI  - Functional recovery after acute myocardial infarction: comparison between
      angiography, electrocardiography, and cardiovascular magnetic resonance measures
      of microvascular injury.
AB  - OBJECTIVES: We examined the relation between angiographic, electrocardiographic,
      and gadolinium-enhanced cardiovascular magnetic resonance (CMR) characteristics
      of microvascular obstruction (MVO), and their predictive value on functional
      recovery after acute myocardial infarction (AMI). BACKGROUND: Microvascular
      obstruction on CMR has been shown to predict left ventricular (LV) remodeling,
      but it is not well known how it compares with commonly used criteria of
      microvascular injury, and earlier reports have produced conflicting results on
      the significance and extent of MVO. METHODS: Thrombolysis In Myocardial
      Infarction (TIMI) flow grade, myocardial blush grade (MBG), and ST-segment
      resolution were assessed in 60 patients with AMI treated with primary stenting.
      Cardiovascular magnetic resonance was performed between 2 and 9 days after
      revascularization to determine early MVO on first-pass perfusion imaging, late
      MVO on late gadolinium-enhanced imaging, and infarct size and transmural extent.
      Cine imaging was used to determine LV volumes and global and regional function at
      baseline and 4-month follow-up. RESULTS: Early and late MVO were both related to
      incomplete ST-segment resolution (p = 0.002 and p = 0.01, respectively), but not
      to TIMI flow grade and MBG. Of all angiographic, electrocardiographic, and CMR
      variables, late MVO was the strongest parameter to predict changes in end
      diastolic volume (beta = 0.53; p = 0.001), end-systolic volume (beta = 8.67; p =
      0.001), and ejection fraction (beta = 3.94; p = 0.006) at follow-up. Regional
      analysis showed that late MVO had incremental diagnostic value to transmural
      extent of infarction (odds ratio: 0.18; p < 0.0001). CONCLUSIONS: In patients
      after revascularized AMI, late MVO proved a more powerful predictor of global and
      regional functional recovery than all of the other characteristics, including
      transmural extent of infarction.

PMID- 18617067
TI  - Influence of beta-blocker continuation or withdrawal on outcomes in patients
      hospitalized with heart failure: findings from the OPTIMIZE-HF program.
AB  - OBJECTIVES: This study ascertains the relationship between continuation or
      withdrawal of beta-blocker therapy and clinical outcomes in patients hospitalized
      with systolic heart failure (HF). BACKGROUND: Whether beta-blocker therapy should
      be continued or withdrawn during hospitalization for decompensated HF has not
      been well studied in a broad cohort of patients. METHODS: The OPTIMIZE-HF
      (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with
      Heart Failure) program enrolled 5,791 patients admitted with HF in a registry
      with pre-specified 60- to 90-day follow-up at 91 academic and community hospitals
      throughout the U.S. Outcomes data were prospectively collected and analyzed
      according to whether beta-blocker therapy was continued, withdrawn, or not
      started. RESULTS: Among 2,373 patients eligible for beta-blockers at discharge,
      there were 1,350 (56.9%) who were receiving beta-blockers before admission and
      continued on therapy, 632 (26.6%) newly started, 79 (3.3%) in which therapy was
      withdrawn, and 303 (12.8%) eligible but not treated. Continuation of beta
      blockers was associated with a significantly lower risk and propensity adjusted
      post-discharge death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.37
      to 0.99, p = 0.044) and death/rehospitalization (odds ratio: 0.69; 95% CI: 0.52
      to 0.92, p = 0.012) compared with no beta-blocker. In contrast, withdrawal of
      beta-blocker was associated with a substantially higher adjusted risk for
      mortality compared with those continued on beta-blockers (HR: 2.3; 95% CI: 1.2 to
      4.6, p = 0.013), but with similar risk as HF patients eligible but not treated
      with beta-blockers. CONCLUSIONS: The continuation of beta-blocker therapy in
      patients hospitalized with decompensated HF is associated with lower post
      discharge mortality risk and improved treatment rates. In contrast, withdrawal of
      beta-blocker therapy is associated with worse risk and propensity-adjusted
      mortality. (Organized Program To Initiate Lifesaving Treatment In Hospitalized
      Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513).

PMID- 18617068
TI  - Sodium nitroprusside for advanced low-output heart failure.
AB  - OBJECTIVES: This study was designed to examine the safety and efficacy of sodium
      nitroprusside (SNP) for patients with acute decompensated heart failure (ADHF)
      and low-output states. BACKGROUND: Inotropic therapy has been predominantly used
      in the management of patients with ADHF presenting with low cardiac output.
      METHODS: We reviewed all consecutive patients with ADHF admitted between 2000 and
      2005 with a cardiac index < or =2 l/min/m(2) for intensive medical therapy
      including vasoactive drugs. Administration of SNP was chosen by the attending
      clinician, nonrandomized, and titrated to a target mean arterial pressure of 65
      to 70 mm Hg. RESULTS: Compared with control patients (n = 97), cases treated with
      SNP (n = 78) had significantly higher mean central venous pressure (15 vs. 13 mm
      Hg; p = 0.001), pulmonary capillary wedge pressure (29 vs. 24 mm Hg; p = 0.001),
      but similar demographics, medications, and renal function at baseline. Use of SNP
      was not associated with higher rates of inotropic support or worsening renal
      function during hospitalization. Patients treated with SNP achieved greater
      improvement in hemodynamic measurements during hospitalization, had higher rates
      of oral vasodilator prescription at discharge, and had lower rates of all-cause
      mortality (29% vs. 44%; odds ratio: 0.48; p = 0.005; 95% confidence interval:
      0.29 to 0.80) without increase in rehospitalization rates (58% vs. 56%; p = NS).
      CONCLUSIONS: In patients with advanced, low-output heart failure, vasodilator
      therapy used in conjunction with optimal current medical therapy during
      hospitalization might be associated with favorable long-term clinical outcomes
      irrespective of inotropic support or renal dysfunction and remains an excellent
      therapeutic choice in hospitalized ADHF patients.

PMID- 18617069
TI  - Vasodilator therapy for decompensated heart failure.

PMID- 18617070
TI  - Extracellular matrix alterations in patients with paroxysmal and persistent
      atrial fibrillation: biochemical assessment of collagen type-I turnover.
AB  - OBJECTIVES: We investigated whether the serum markers of collagen turnover
      differed in various forms of atrial fibrillation (AF) and in sinus rhythm (SR) in
      humans. BACKGROUND: Structural alterations and fibrosis have been implicated in
      the generation and perpetuation of AF. METHODS: Serum C-terminal propeptide of
      collagen type-I (CICP), C-terminal telopeptide of collagen type-I (CITP), matrix
      metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were
      measured as markers of collagen synthesis and degradation in 70 patients with AF
      and 20 healthy control subjects in SR. RESULTS: C-terminal propeptide of collagen
      type-I and CITP were significantly higher in AF patients than in control subjects
      (91 +/- 27 ng/ml vs. 67 +/- 11 ng/ml, p < 0.001 and 0.38 +/- 0.20 ng/ml vs. 0.25
      +/- 0.08 ng/ml, p < 0.001, respectively). Persistent AF patients had higher
      levels of CICP (105 +/- 28 ng/ml vs. 80 +/- 21 ng/ml, p < 0.001), but not CITP,
      compared with those with paroxysmal AF. Patients with persistent AF had lower
      levels of matrix metalloproteinase-1 but increased levels of tissue inhibitor of
      matrix metalloproteinases-1 compared with patients with paroxysmal AF (11.90 +/-
      4.79 ng/ml vs. 14.98 +/- 6.28 ng/ml, p = 0.03 and 155 +/- 45 ng/ml vs. 130 +/- 38
      ng/ml, p < 0.001, respectively). Tissue inhibitor of matrix metalloproteinases-1
      levels were significantly lower in control subjects compared with those in both
      paroxysmal and persistent AF patients (102 +/- 15 ng/ml vs. 130 +/- 38 ng/ml vs.
      155 +/- 45 ng/ml, respectively, p < 0.001). CONCLUSIONS: Serum markers of
      collagen type-I turnover differed significantly between patients with AF and SR.
      Furthermore, these markers also differed significantly between paroxysmal and
      persistent AF patients, suggesting that the intensity of the extracellular
      synthesis and degradation of collagen type-I may be related to the burden or type
      of AF.

PMID- 18617071
TI  - Noninvasive evaluation with multislice computed tomography in suspected acute
      coronary syndrome: plaque morphology on multislice computed tomography versus
      coronary calcium score.
AB  - OBJECTIVES: Our aim was to evaluate the atherosclerotic plaque burden and
      morphology as determined by 64-slice multislice computed tomography (MSCT)
      coronary angiography in relation to the calcium score in patients presenting with
      suspected acute coronary syndrome (ACS). BACKGROUND: The absence of coronary
      calcium during coronary calcium scoring has been proposed to rule out significant
      coronary artery disease (CAD). However, data in patients presenting with
      suspected ACS are scarce. METHODS: In 40 patients (age 57 +/- 11 years, 26 men)
      presenting with suspected ACS, MSCT coronary angiography in combination with
      coronary calcium scoring was performed before conventional coronary angiography.
      MSCT angiograms were evaluated for the presence or absence of coronary
      atherosclerotic plaque and the presence or absence of obstructive (> or =50%
      luminal narrowing) CAD. In addition, plaque type was determined, and findings
      were related to the calcium score. RESULTS: Coronary artery disease was observed
      in 38 patients, of whom 10 patients had nonobstructive and 28 patients had
      obstructive CAD, confirmed by conventional coronary angiography in all patients.
      In patients with CAD, plaques were distributed as follows: 39% noncalcified
      plaques, 47% mixed plaques, and 14% calcified plaques. Coronary calcium was
      detected in 27 patients, of whom 10 had a score >400. In 13 (33%) patients, no
      coronary calcium was observed, but in 11 (85%), atherosclerotic plaques were
      detected on MSCT angiography. CONCLUSIONS: In patients presenting with suspected
      ACS, noncalcified plaques are highly prevalent and the absence of coronary
      calcium does not reliably exclude the presence of (significant) atherosclerosis.
      This information may be of value to improve our understanding of the potential
      role of MSCT in this patient population.

PMID- 18617072
TI  - Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid
      arteries: correlation with histology and plaque echogenicity.
AB  - OBJECTIVES: This study was designed to evaluate contrast-enhanced ultrasound
      imaging of carotid atherosclerosis as a clinical tool to study intraplaque
      neovascularization. BACKGROUND: Plaque neovascularization is associated with
      plaque vulnerability and symptomatic disease; therefore, imaging of
      neovascularization in carotid atherosclerosis may represent a useful tool for
      clinical risk stratification and monitoring the efficacy of antiatherosclerotic
      therapies. METHODS: Thirty-two patients with 52 carotid plaques were studied by
      standard and contrast-enhanced ultrasound imaging. In 17 of these patients who
      underwent endarterectomy, the surgical specimen was available for histological
      determination of microvessel density by CD31/CD34 double staining. Plaque
      echogenicity and degree of stenosis at standard ultrasound imaging were evaluated
      for each lesion. Contrast-agent enhancement within the plaque was categorized as
      absent/peripheral (grade 1) and extensive/internal (grade 2). RESULTS: In the
      surgical subgroup, plaques with higher contrast-agent enhancement showed a
      greater neovascularization at histology (grade 2 vs. grade 1 contrast-agent
      enhancement: median vasa vasorum density: 3.24/mm(2) vs. 1.82/mm(2),
      respectively, p = 0.005). In the whole series of 52 lesions, echolucent plaques
      showed a higher degree of contrast-agent enhancement (p < 0.001). Stenosis degree
      was not associated with neovascularization at histology or with the grade of
      contrast-agent enhancement. CONCLUSIONS: Carotid plaque contrast-agent
      enhancement with sonographic agents correlates with histological density of
      neovessels and is associated with plaque echolucency, a well-accepted marker of
      high risk lesions, but it is unrelated to the degree of stenosis. Contrast
      enhanced carotid ultrasound imaging may provide valuable information for plaque
      risk stratification and for assessing the response to antiatherosclerotic
      therapies, beyond that provided by standard ultrasound imaging.

PMID- 18617074
TI  - Meta-analysis.

PMID- 18617073
TI  - Adipokines, insulin resistance, and coronary artery calcification.
AB  - OBJECTIVES: We evaluated the hypothesis that plasma levels of adiponectin and
      leptin are independently but oppositely associated with coronary artery
      calcification (CAC), a measure of subclinical atherosclerosis. In addition, we
      assessed which biomarkers of adiposity and insulin resistance are the strongest
      predictors of CAC beyond traditional risk factors, metabolic syndrome, and plasma
      C-reactive protein (CRP). BACKGROUND: Adipokines are fat-secreted biomolecules
      with pleiotropic actions that converge in diabetes and cardiovascular disease.
      METHODS: We examined the association of plasma adipocytokines with CAC in 860
      asymptomatic, nondiabetic participants in the SIRCA (Study of Inherited Risk of
      Coronary Atherosclerosis). RESULTS: Plasma adiponectin and leptin levels had
      opposite and distinct associations with adiposity, insulin resistance, and
      inflammation. Plasma leptin was positively (top vs. bottom quartile) associated
      with higher CAC after adjustment for age, gender, traditional risk factors, and
      Framingham risk scores (tobit regression ratio 2.42 (95% confidence interval
      [CI]: 1.48 to 3.95; p = 0.002) and further adjustment for metabolic syndrome and
      CRP (tobit regression ratio: 2.31; 95% CI: 1.36 to 3.94; p = 0.002). In contrast,
      adiponectin levels were not associated with CAC. Comparative analyses suggested
      that levels of leptin, interleukin-6, and soluble tumor necrosis factor receptor
      2, as well as the homeostasis model assessment of insulin resistance (HOMA-IR)
      index, predicted CAC scores, but only leptin and HOMA-IR provided value beyond
      risk factors, metabolic syndrome, and CRP. CONCLUSIONS: In SIRCA, although both
      leptin and adiponectin levels were associated with metabolic and inflammatory
      markers, only leptin was a significant independent predictor of CAC. Of several
      metabolic markers, leptin and the HOMA-IR index had the most robust, independent
      associations with CAC.

PMID- 18617075
TI  - Insulin resistance in chronic heart failure.

PMID- 18617077
TI  - Promoting prostate-specific antigen informed decision-making. Evaluating two
      community-level interventions.
AB  - BACKGROUND: Most medical associations recommend that patients make informed
      decisions about whether to be screened for prostate cancer with the prostate
      specific antigen (PSA) test. Studies assessing how to promote PSA informed
      decision-making (IDM) have been conducted almost exclusively in healthcare
      settings; there is a need for similar research in community settings. METHODS:
      This paper describes the results of a 5-year study (2002--2007) in which two
      community-level interventions were developed, implemented, and evaluated in
      matched upper- and lower-SES comparison communities in Greensboro and Wilmington,
      North Carolina. Both interventions promoted PSA informed decision-making. One
      intervention (PSA-Only) consisted of educational information about prostate
      cancer and the PSA test, and the other (Men's Health) included additional
      information about recognizing and preventing heart attack, stroke, and colon
      cancer. Structured survey, semistructured interview, and structured observational
      data were combined to compare participating community residents' pre/post changes
      in knowledge, intentions, and behaviors related to PSA IDM. RESULTS: The
      community-level interventions successfully engaged community participants in
      discussions, educated individuals, encouraged deliberation of information, and
      facilitated PSA test discussions with physicians. Men who participated in the PSA
      Only educational sessions were more likely than those who attended the Men's
      Health educational sessions to discuss the PSA test with their physician
      (p=0.037). CONCLUSIONS: When prospective SES-related confounding factors are
      matched across comparison communities, PSA IDM interventions can be shown to
      promote IDM. Framing the PSA test decision relative to less-ambiguous screening
      decisions does not appear to increase the likelihood of PSA IDM.

PMID- 18617078
TI  - Exposure to smoking imagery in popular films and adolescent smoking in Mexico.
AB  - BACKGROUND: Exposure to smoking imagery in films is consistently associated with
      smoking behavior and its psychological antecedents among adolescents in high
      income countries, but its association with adolescent smoking in middle-income
      countries is unknown. METHODS: In 2006, a cross-sectional sample of 3876 Mexican
      adolescents in secondary school was surveyed on smoking behavior, smoking risk
      factors, and exposure to 42 popular films that contained smoking. Participants
      were classified into quartiles of exposure to smoking imagery across all films
      they reported having seen. Models were estimated to determine associations among
      quartiles of film-smoking exposure, smoking behavior, and the psychological
      antecedents of smoking, adjusting for age, gender, sensation seeking, self
      esteem, parental smoking, sibling smoking, best-friend smoking, having a bedroom
      TV, and private versus public school attendance. Analyses were conducted in 2007.
      RESULTS: Adolescents were exposed to an average of 51.7 (SE=1.3) minutes of
      smoking in the films they viewed. Crude and adjusted ORs indicated positive
      associations between quartiles of film-smoking exposure and both current smoking
      (AOR4v1=3.13; p<0.0001) and having ever smoked (AOR4v1=2.42; p<0.0001). Data from
      never-smokers (n=2098) were analyzed to determine associations between film
      smoking exposure and psychological antecedents of smoking uptake. Crude and
      adjusted coefficients indicated significant, positive associations between
      exposure and susceptibility to smoking (AOR4v1=1.66; p<0.05); favorable attitudes
      toward smoking (Adjusted B4v1=0.44; p<0.0001); and perceived peer prevalence of
      smoking (Adjusted B4v1=0.26; p<0.0001). CONCLUSIONS: Exposure to smoking in films
      appears associated with smoking among Mexican adolescents. Policies could aim to
      decrease youth exposure to smoking in nationally and internationally distributed
      films.

PMID- 18617079
TI  - Nicotine patches and uninsured quitline callers. A randomized trial of two versus
      eight weeks.
AB  - BACKGROUND: State-level tobacco quitlines are integrating nicotine replacement
      therapy (NRT) into service. Because of funding limitations some provide short
      courses of NRT. No randomized trial has evaluated the relative benefit of short
      versus standard treatment. DESIGN: A two-cell randomized trial comparing 2 weeks
      of NRT to 8 weeks. SETTING/PARTICIPANTS: Uninsured callers to the Oregon Quit
      Line during a free-patch initiative from October 18, 2004, to May 5, 2005, who
      were 18 years or older, smoked five or more cigarettes per day, did not have a
      medical contraindication to NRT use, and were interested in quitting in 30 days.
      Data were collected from April to November 2005, and analyzed in 2006--2007.
      INTERVENTION: Participants were eligible for two phone counseling sessions. 1154
      participants were randomized to receive via the mail either 2 or 8 weeks of
      nicotine patches. MEASURES: Primary outcome was self-reported complete abstinence
      from tobacco for 30 or more days at the 6-month phone survey. Secondary outcomes
      were 7-day point prevalence and 90-day abstinence, satisfaction, and patch use.
      ORs and CIs were computed. Cost per quit and incremental cost per additional quit
      were computed based on program costs. RESULTS: Intent-to-treat 30-day abstinence
      was 14.3% in the 2-week group, and 19.6% in the 8-week group (OR 1.45 [CI=1.01,
      2.12]). Average cost per quit was $1156 for 2 weeks and $1405 for 8 weeks, with
      an incremental cost effectiveness of $2068. Satisfaction increased from 90% to
      97% with 8 weeks. Those receiving 8 weeks of NRT took more calls (2.0 vs 1.6) and
      used more patches (6.3 weeks vs 4.3 weeks), but were less likely to purchase
      patches (16.2% vs 39.3%). CONCLUSIONS: Eight weeks of patches improved quit rates
      compared with 2 weeks, and was cost effective.

PMID- 18617080
TI  - Weight loss during the intensive intervention phase of the weight-loss
      maintenance trial.
AB  - BACKGROUND: To improve methods for long-term weight management, the Weight Loss
      Maintenance (WLM) trial, a four-center randomized trial, was conducted to compare
      alternative strategies for maintaining weight loss over a 30-month period. This
      paper describes methods and results for the initial 6-month weight-loss program
      (Phase I). METHODS: Eligible adults were aged > or =25, overweight or obese
      (BMI=25-45 kg/m2), and on medications for hypertension and/or dyslipidemia.
      Anthropomorphic, demographic, and psychosocial measures were collected at
      baseline and 6 months. Participants (n=1685) attended 20 weekly group sessions to
      encourage calorie restriction, moderate-intensity physical activity, and the DASH
      (dietary approaches to stop hypertension) dietary pattern. Weight-loss predictors
      with missing data were replaced by multiple imputation. RESULTS: Participants
      were 44% African American and 67% women; 79% were obese (BMI> or =30), 87% were
      taking anti-hypertensive medications, and 38% were taking antidyslipidemia
      medications. Participants attended an average of 72% of 20 group sessions. They
      self-reported 117 minutes of moderate-intensity physical activity per week, kept
      3.7 daily food records per week, and consumed 2.9 servings of fruits and
      vegetables per day. The Phase-I follow-up rate was 92%. Mean (SD) weight change
      was -5.8 kg (4.4), and 69% lost at least 4 kg. All race-gender subgroups lost
      substantial weight: African-American men (-5.4 kg +/- 7.7); African-American
      women (-4.1 kg +/- 2.9); non-African-American men (-8.5 kg +/- 12.9); and non
      African-American women (-5.8 kg +/- 6.1). Behavioral measures (e.g., diet records
      and physical activity) accounted for most of the weight-loss variation, although
      the association between behavioral measures and weight loss differed by race and
      gender groups. CONCLUSIONS: The WLM behavioral intervention successfully achieved
      clinically significant short-term weight loss in a diverse population of high
      risk patients.

PMID- 18617081
TI  - Cancer screening among the overweight and obese in Canada.
AB  - BACKGROUND: Despite increased cancer incidence and mortality among overweight and
      obese men and women, U.S. studies have reported the reduced use of cancer
      screening among these subjects. We sought to analyze the relationship between
      overweight/obesity and cancer screening practices using population-based Canadian
      data. METHODS: Responses from adults surveyed in the Canadian Community Health
      Survey 2003 who provided complete information regarding variables of interest
      were analyzed. Cancer screening modalities included Pap smear testing,
      mammography, and fecal occult blood testing, and were based on contemporary
      recommendations of the Canadian Task Force for Preventive Health. The association
      between overweight/obesity and cancer screening was explored using logistic
      regression after adjusting for demographic and socioeconomic factors, health
      habits, healthcare access, and obesity-related comorbidity. The analysis was
      conducted in 2007. RESULTS: Compared to normal-weight controls, overweight and
      obese women were significantly less likely to have undergone cervical cancer
      screening. In the fully adjusted model, increasing obesity was associated with
      decreasing odds of Pap smear testing, with overweight, Class-I, -II, and -III
      obesity having 95% ORs of 0.87 (0.81, 0.94); 0.79 (0.72, 0.88); 0.62 (0.54,
      0.71); and 0.61 (0.53, 0.72), respectively. The prevalence of biennial breast and
      colorectal cancer screenings was largely unaffected by weight in the adjusted
      analyses. CONCLUSIONS: Overweight and obesity are associated with markedly lower
      utilization of cervical cancer screening, despite increased disease risks. This
      association is independent of sociodemographic factors, comorbidity, and
      healthcare access. This is consistent with findings in U.S. populations, and
      suggests that patient and provider factors serve as greater barriers to screening
      than do healthcare system factors.

PMID- 18617082
TI  - Social capital and health. A study of adult twins in the U.S.
AB  - BACKGROUND: A growing number of studies have suggested a link between social
      capital and health. However, the association may reflect confounding by factors,
      such as personality or early childhood environment, that are unmeasured prior
      common causes of both social capital and health outcomes. The purpose of this
      study was to investigate the impact of social capital on physical and mental
      health among adult twins in the U.S. METHODS: A cross-sectional national survey
      of twins within the National Survey of Midlife Development in the U.S. (MIDUS),
      1995--1996 was analyzed in 2007. The study population included 944 twin pairs
      (37.2% monozygotic [MZ] and 62.8% dizygotic [DZ]). Data were obtained on
      individual-level social capital variables (social trust, sense of belonging,
      volunteer activity, and community participation); health outcomes (perceived
      physical and mental health, depressive symptoms and major depression); and
      individual covariates (age, gender, race, education, working status, and marital
      status). A fixed-effects model was used to examine health status among twin pairs
      who were discordant on levels of social capital. RESULTS: In the individual data
      analysis, social trust, sense of belonging, and community participation were each
      significantly associated with health outcomes. In the fixed-effects model,
      physical health remained significantly positively associated with social trust
      among MZ and DZ twins. However, major depression was not associated with social
      capital. CONCLUSIONS: The present study is the first to find the independent
      positive effect of social trust on self-rated physical health using fixed-effects
      models of twin data. The results suggest that the association between social
      capital and physical health status is not explained by unobserved confounds, such
      as personality or early childhood environment.

PMID- 18617083
TI  - Mandates for adolescent immunizations: recommendations from the National Vaccine
      Advisory Committee.

PMID- 18617084
TI  - The promise and challenge of adolescent immunization.

PMID- 18617086
TI  - The effects of social capital on health. What twin studies can tell us.

PMID- 18617087
TI  - Acute HIV infection increases the dangers of serosorting.

PMID- 18617089
TI  - Early bisphenol-A studies negative for orthodontic adhesives.

PMID- 18617085
TI  - A clinical practice guideline for treating tobacco use and dependence: 2008
      update. A U.S. Public Health Service report.
AB  - OBJECTIVE: To summarize the U.S. Public Health Service guideline Treating Tobacco
      Use and Dependence: 2008 Update, which provides recommendations for clinical
      interventions and system changes to promote the treatment of tobacco dependence.
      PARTICIPANTS: An independent panel of 24 scientists and clinicians selected by
      the U.S. Agency for Healthcare Research and Quality on behalf of the U.S. Public
      Health Service. A consortium of eight governmental and nonprofit organizations
      sponsored the update. EVIDENCE: Approximately 8700 English-language, peer
      reviewed articles and abstracts, published between 1975 and 2007, were reviewed
      for data that addressed assessment and treatment of tobacco dependence. This
      literature served as the basis for more than 35 meta-analyses. CONSENSUS PROCESS:
      Two panel meetings and numerous conference calls and staff meetings were held to
      evaluate meta-analyses and relevant literature, to synthesize the results, and to
      develop recommendations. The updated guideline was then externally reviewed by
      more than 90 experts, made available for public comment, and revised.
      CONCLUSIONS: This evidence-based, updated guideline provides specific
      recommendations regarding brief and intensive tobacco-cessation interventions as
      well as system-level changes designed to promote the assessment and treatment of
      tobacco use. Brief clinical approaches for patients willing and unwilling to quit
      are described.

PMID- 18617090
TI  - Radiographic and periodontal requirements of the American Board of Orthodontics:
      a modification in the case display requirements for adult and periodontally
      involved adolescent and preadolescent patients.

PMID- 18617092
TI  - Self-ligating brackets.

PMID- 18617093
TI  - Extraction and evidence-based decision making.

PMID- 18617095
TI  - In-vitro fluoride release.

PMID- 18617096
TI  - Skeletal effects to the maxilla after rapid maxillary expansion assessed with
      cone-beam computed tomography.
AB  - INTRODUCTION: The purpose of this study was to use cone-beam computed tomography
      to quantitatively evaluate skeletal expansion and alveolar tipping of the maxilla
      at the maxillary canine (C1), first premolar (P1), second premolar (P2), and
      first molar (M1) after rapid maxillary expansion (RME). The transverse effects to
      the maxillary suture, nasal width, and maxillary sinus were also assessed.
      METHODS: Thirty consecutive patients (17 boys, 13 girls; mean age, 13.8 +/- 1.7
      years) who required RME with Hyrax appliances as part of their comprehensive
      orthodontic treatment were studied. Measurements before and after RME of palatal
      and buccal maxillary widths, palatal alveolar angle, nasal width, nasal floor
      width, and maxillary sinus width at C1, P1, P2, and M1 were compared by using
      Wilcoxon signed rank, Kruskal-Wallis, and Wilcoxon rank sum tests. Pearson
      correlation analyses were also performed (* = .05). RESULTS AND CONCLUSIONS:
      Skeletal expansion of the maxilla had a triangular pattern with a wider base in
      the anterior region, accounting for 55% of total expansion at P1, 45% at P2, and
      38% at M1. Alveolar bending or tipping accounted for 6% of total expansion at P1,
      9% at P2, and 13% at M1. The remaining orthodontic (dental tipping) portions of
      total expansion were 39% at P1, 46% at P2, and 49% at M1. RME produces a
      statistically significant increase in nasal width and a decrease in maxillary
      sinus width (P <0.0001). Retention time showed a significant negative correlation
      to the change in palatal maxillary width at C1, P2, and M1 (P <0.05), the rate of
      appliance expansion had a significant correlation with palatal maxillary
      expansion at P1 and P2 (P <0.05), and age had no statistically significant
      association with any parameter (P >0.05).

PMID- 18617097
TI  - Evaluation of anterior open-bite treatment with occlusal adjustment.
AB  - INTRODUCTION: The purpose of this study was to evaluate the cephalometric and
      occlusal changes, the functional occlusion, and the dentinal sensitivity of
      anterior open-bite treatment with occlusal adjustment. METHODS: The sample
      comprised 20 patients who experienced relapse of the anterior open bite (mean, 
      1.06 mm). Occlusal adjustment was performed until a positive overbite was
      established. Cephalometric changes were evaluated on lateral cephalograms taken
      before and after the occlusal adjustment. The functional occlusion analysis
      consisted of evaluating immediate anterior and canine guidance and the number of
      teeth in contact before and after the procedure. Dentinal sensitivity was
      evaluated before, shortly after, and 4.61 months after the occlusal adjustment.
      Pretreatment and posttreatment cephalometric changes and the number of teeth in
      contact were compared with dependent t tests. Percentages of anterior and canine
      guidance before and after the adjustment procedure were compared with the McNemar
      test. To compare dentinal sensitivity at several stages, the nonparametric
      Friedman test was used, followed by the Wilcoxon test. RESULTS: Significant
      increases in overbite and mandibular protrusion were seen, as were significant
      decreases in apical base discrepancy, facial convexity, and growth pattern
      angles. The percentages of immediate anterior and canine guidance increased
      significantly, as did the number of teeth with occlusal contacts. Dentinal
      sensitivity increased immediately after the adjustment but decreased to normal
      levels after 4.61 months. CONCLUSIONS: Occlusal adjustment is a viable treatment
      alternative for some open-bite patients; it establishes positive vertical
      overbite and improves the functional occlusion with only transient dentinal
      sensitivity.

PMID- 18617098
TI  - Influence of orthodontic intrusion on pulpal vitality of previously traumatized
      maxillary permanent incisors.
AB  - INTRODUCTION: Dental trauma seems to increase a patient's susceptibility to
      complications during orthodontic treatment. However, no previous investigation
      has examined the influence of orthodontic intrusion on pulpal vitality of
      traumatized maxillary permanent incisors. METHODS: Pulpal condition was examined
      clinically and radiologically after orthodontic intrusion of previously
      traumatized (OT group) and nontraumatized teeth (O group), and after previous
      dental trauma without orthodontic treatment (T group). Inclusion criteria for the
      OT and O groups were Class II Division 1 malocclusion with deep bite and
      orthodontic intrusion of the maxillary incisors, no extractions of maxillary
      teeth, and no additional lateral tooth movement of the maxillary incisors. All
      teeth in the OT group had a positive sensitivity test before orthodontic therapy.
      RESULTS: Teeth in the OT group, and especially those with severe periodontal
      injuries, showed a significantly higher frequency of pulp necrosis than teeth in
      the O and T groups. The occurrence of pulp necrosis was significantly higher in
      lateral than in central incisors. CONCLUSIONS: Traumatized maxillary incisors,
      and especially lateral incisors, with severe periodontal injuries have a higher
      susceptibility to pulp necrosis during orthodontic intrusion than nontraumatized
      teeth.

PMID- 18617099
TI  - Treatment effects of mini-implants for en-masse retraction of anterior teeth in
      bialveolar dental protrusion patients: a randomized controlled trial.
AB  - INTRODUCTION: The purpose of this randomized controlled trial was to quantify the
      treatment effects of en-masse retraction of anterior teeth with mini-implants as
      anchor units in bialveolar dental protrusion patients undergoing extraction of
      all 4 first premolars. METHODS: A total of 40 patients (mean age, 17.5 years; SD,
      3.2 years) were randomly assigned either to group 1 (G1), anterior space closure
      with mini-implants as anchor units, or group 2 (G2), anterior space closure with
      conventional methods of anchorage (without mini-implants). Skeletal, dental, and
      soft-tissue changes were analyzed in both groups on lateral cephalograms taken
      before retraction and after space closure. RESULTS: Student paired and unpaired t
      tests were used to analyze the treatment changes in the 2 groups. For the
      skeletal parameters, a statistically significant decrease in the facial vertical
      dimensions was seen in G1, but the variables in G2 showed no significant
      differences (P >0.05). Anchorage loss, in both the horizontal and vertical
      directions, was noted in G2, whereas G1 showed distalization (anchorage gain) and
      intrusion of molars. Although the soft-tissue response was variable, facial
      convexity angle, nasolabial angle, and lower lip protrusion had greater changes
      in G1. No differences were found in the amount of upper lip retraction between
      the groups (P >0.05). CONCLUSIONS: Mini-implants provided absolute anchorage to
      allow greater skeletal, dental, and esthetic changes in patients requiring
      maximum anterior retraction, when compared with other conventional methods of
      space closure. The treatment changes were favorable. However, no differences in
      the mean retraction time were noted between the 2 groups.

PMID- 18617100
TI  - Comparison of rate of canine retraction with conventional molar anchorage and
      titanium implant anchorage.
AB  - INTRODUCTION: Various anchorage techniques have been designed for canine
      retraction. Intraoral techniques have not always been successful, and now
      implants are widely used for this purpose. A new type of titanium microimplant,
      with a small diameter and a button-like head, was shown to be an effective source
      of anchorage for distal movement of the canines. The purposes of this study were
      to measure and compare the rates of canine retraction with titanium microimplant
      anchorage and conventional molar anchorage. METHODS: The sample comprised 12
      patients (8 female, 4 male; mean age, 19.7 years; range, 16-22 years) who were
      scheduled for extraction of all first premolars. After leveling and aligning,
      titanium microimplants 1.2 mm in diameter and 9 mm in length were placed between
      the roots of the second premolar and the first molars. The implants were placed
      in the maxillary and mandibular arches on the same side in 10 patients and in the
      maxilla only in 2 patients. A brass wire guide and a periapical radiograph were
      used to determine the implant position. After 15 days, the implants and the
      molars were loaded with closed coil springs with a force of 100 g for canine
      retraction. Preretraction and postretraction lateral cephalograms were taken and
      superimposed for measuring the amount of retraction. The amount of canine
      retraction was measured from pterygoid vertical in the maxilla and SN
      perpendicular in the mandible. RESULTS: Mean canine retraction amounts were 4.29
      mm in the maxilla and 4.10 mm in the mandible on the implant-anchorage side, and
      3.79 mm in the maxilla and 3.75 mm in the mandible on the molar-anchorage side.
      The rates of canine retraction were 0.93 mm per month in the maxilla and 0.83 mm
      per month in the mandible on the implant-anchored side, and 0.81 mm per month in
      the maxilla and 0.76 mm per month in the mandible on the molar-anchored side.
      CONCLUSIONS: Canine retraction proceeds at a faster rate when titanium
      microimplants are used for anchorage.

PMID- 18617101
TI  - Removal torque values of surface-treated mini-implants after loading.
AB  - INTRODUCTION: Although the sand-blasted, large-grit, and acid-etched surface
      treated mini-implant (C-implant, CImplant Co, Seoul, South Korea) is designed to
      endure heavy and dynamic loads and offers high stability during orthodontic
      treatment, implications of its removal are still unknown. The purpose of this
      study was to evaluate the removal torque values (RTVs) of early-loaded mini
      implants. METHODS: Sixty-four mini-implants (1.8 mm in diameter and 8.5 mm in
      length) were placed in 37 patients for orthodontic anchorage and were subjected
      to early loading (4 weeks healing period). RTVs were recorded after orthodontic
      treatment by using a digital torque driver that was calibrated on a torque
      sensor. Torque values were subjected to a paired t test and analysis of variance
      (P <0.05). RESULTS: All mini-implants remained intact, for a 100% success rate.
      There was no fracture or distortion during removal, and the mean RTV was 16.4 N
      per centimeter (range, 3.94-35.41 N per centimeter). Age, malocclusion, and
      loading period were not significantly related to the RTVs. The longer nonloading
      period from debonding to removal had a higher RTV. The RTV measured over 6 months
      of the nonloading period showed a significantly higher RTV than the group
      measured less than 6 months of the nonloading period. CONCLUSIONS: Surface
      treated mini-implants can be safely removed after treatment. A nonloading period
      of less than 6 months before removal is recommended to prevent complications.

PMID- 18617102
TI  - Sequential bone healing of immediately loaded mini-implants.
AB  - INTRODUCTION: The relatively small size and the ability to load mini-implants
      without delay are important changes in the simplification of bone rigid
      anchorage. The purpose of this study was to analyze interfacial healing 1, 4, and
      12 weeks after the placment of titanium mini-implants in New Zealand rabbits by
      removal torque test (RTT) and scanning electron microscopy (SEM). METHODS:
      Eighteen animals were used in the experiment, in which 72 titanium grade 5 mini
      implants 2.0 mm in diameter and 6.0 mm long, were placed. Each animal received 4
      mini-implants; 2 were immediately loaded with 1 N. RESULTS: The RTT means for the
      unloaded mini-implants at 1, 4, and 12 weeks were 15.2 +/- 4.2 N mm (n = 5), 13.1
      +/- 5.7 N mm (n = 5), and 54.4 +/- 12.8 N mm (n = 4), respectively. The loaded
      groups had means of 12.7 +/- 5.1 N mm (n = 4), 11.1 +/- 5.4 N mm (n = 4), and
      32.9 +/- 12.8 N mm (n = 5) for the same healing periods, respectively. The
      statistical evaluation indicated significance in the comparison between loaded
      and unloaded 12-week groups (P <0.05). SEM analysis in the loaded group showed
      the formation of less fibrous interfacial tissue after 4 weeks and more lamellar
      appearance after 12 weeks. CONCLUSIONS: The immediate 1-N load did not cause
      significant changes in the fixation of the mini-implants after 1 and 4 weeks of
      bone healing. Nevertheless, after 12 weeks, the loaded group had significantly
      lower RTT values than the unloaded group without compromising the stability of
      the mini-implants (P <0.05).

PMID- 18617103
TI  - Sutural strain in orthopedic headgear therapy: a finite element analysis.
AB  - INTRODUCTION: The goal of this study was to analyze the strains induced in the
      sutures of the midface and the cranial base by headgear therapy involving
      orthopedic forces. Does the mechanical signal induced in the sutures sufficiently
      account for a growth-influencing effect? METHODS: A finite element model of the
      viscerocranium and the neurocranium was used. It consisted of 53,555 tetrahedral
      elements and 97,550 nodes. The strain induced in the sutures of the cranial base
      and the midface when applying orthopedic headgear forces of 5 and 10 N was
      computed and recorded with an interactive measurement tool. RESULTS: The
      magnitude and the distribution of the measured strains depended on the level and
      the direction of the acting force. Overall, the strain values measured at the
      sutures of the midface and the cranial base were moderate. The measured peak
      values at a load of 5 N per side were usually just below 20 microstrain
      irrespective of the force direction. A characteristic distribution of strain
      values appeared on the anatomical structures of the midface and the cranial base
      for each vector direction. The measurements based on the finite element method
      provided a good overview of the approximate magnitudes of sutural strains with
      orthopedic headgear therapy. The signal arriving in the sutures is apparently
      well below threshold, since the maximum measured strains in most sutures were
      about 100 fold lower than the minimal effective strain. A skeletal effect of the
      orthopedic headgear due to a mechanical effect on sutural growth cannot be
      confirmed from these results. CONCLUSIONS: The good clinical efficacy of headgear
      therapy with orthopedic forces is apparently based mainly on dentoalveolar
      effects, whereas the skeletal effect due to inhibition of sutural growth is
      somewhat questionable.

PMID- 18617104
TI  - Three-year stability of open-bite correction by 1-piece maxillary osteotomy.
AB  - INTRODUCTION: The purpose of this retrospective cephalometric study was to
      evaluate the long-term vertical stability of anterior open-bite correction by 1
      piece Le Fort I osteotomy and rigid fixation. METHODS: The sample comprised 40
      consecutively treated patients from the files of the Department of Orthodontics,
      University of Oslo, Norway. All subjects had received a 1-piece Le Fort I
      osteotomy as the only surgical procedure from 1990 through 1998 and were followed
      for 3 years according to a protocol for data collection. Lateral cephalograms
      were obtained before surgery and at 5 occasions after surgery. RESULTS: The mean
      open bite before surgery was 2.6 mm; at the 3-year follow-up, 35 patients had a
      positive overbite, and the remaining 5 patients had an open bite between 0.2 and
      0.9 mm. Impaction of the posterior maxilla >or=2 mm relapsed on average by 31%,
      and inferior repositioning of the anterior maxilla >or=2 mm relapsed by 62%.
      Maxillary vertical skeletal changes during the postsurgery period were
      compensated for by orthodontic dentoalveolar adaptation. Most of the skeletal
      relapse occurred during the first 6 months after surgery and always in the
      direction opposite to the surgical movement. The relative contribution of
      mandibular and maxillary changes in anterior open-bite closure was approximately
      3:1. CONCLUSIONS: Surgical correction of anterior open bite was generally stable
      over a 3-year period, and skeletal relapse was counteracted by dentoalveolar
      compensation.

PMID- 18617105
TI  - Comparison of titanium and resorbable copolymer fixation after Le Fort I
      maxillary impaction.
AB  - INTRODUCTION: Advances in skeletal stabilization techniques have led to the use
      of titanium devices for rigid fixation. Their advantages include strength and
      skeletal stability, but they also have disadvantages. The purpose of this study
      was to investigate the stability of a resorbable copolymer as a potential
      alternative to titanium for fixation of Le Fort I maxillary impaction. METHODS:
      Fifty consecutive patients underwent maxillary impaction with nonsegmental
      monopiece Le Fort I osteotomy. Twenty-five patients were treated with titanium
      fixation; 25 patients were treated with resorbable copolymer fixation (82% poly-L
      lactic acid: 18% polyglycolic acid). Lateral cephalograms were obtained 1 week
      preoperatively, 1 week postoperatively, and a minimum of 8 months
      postoperatively. Linear and angular measurements were recorded digitally to
      evaluate 2-dimensional skeletal changes. RESULTS: Statistical analysis showed no
      significant radiographic differences (P <0.05) in long-term stability in or
      between the 2 groups. No clinical or radiographic evidence of wound healing
      problems was noted. CONCLUSIONS: These results support the use of resorbable
      copolymer fixation for Le Fort I impaction as a viable alternative to titanium
      fixation.

PMID- 18617106
TI  - . Facial attractiveness: ranking of end-of-treatment facial photographs by pairs
      of Chinese and US orthodontists.
AB  - INTRODUCTION: In this study, we assessed agreement and disagreement among pairs
      of Chinese and US orthodontists in the ranking for "facial attractiveness" of end
      of-treatment photographs of growing Chinese and white orthodontic patients.
      METHODS: Two groups of orthodontist-judges participated: from the University of
      the Pacific, School of Dentistry, in California and from Peking University School
      and Hospital of Stomatology in China. Each judge independently ranked standard
      clinical sets of profile, frontal, and frontal-smiling photographs of 43 white
      patients and 48 Chinese patients. Pearson correlations were generated for a total
      of 1980 rankings by pairs of judges. RESULTS: The resulting correlations ranged
      from +0.004 to +0.96 with a median of +0.54. Of these, 18.7% were lower than 0.4;
      41.0% were lower than 0.5; 68.8% were lower than 0.6; 91.6% were lower than 0.7;
      and only 8.4% were greater than 0.7. As had been anticipated, correlations
      between judges were higher when they ranked patients of their own ethnicity than
      when they ranked patients of different ethnicity, but the differences were
      smaller than had been expected. The rankings of no pair of judges correlated
      negatively. This is to say that no pair of judges, whether of the same or
      different ethnicity, ranked the patients so that those 1 judge tended to find
      attractive were consistently found unattractive by the other. CONCLUSIONS: The
      distribution of levels of agreement between pairs of orthodontists did not differ
      substantially whether the pairs included 2 US orthodontists, 2 Chinese
      orthodontists, or 1 US and 1 Chinese orthodontist. As might be expected, the
      pairs of Chinese orthodontists agreed with each other slightly better on average
      when ranking Chinese patients, and the pairs of US orthodontists agreed with each
      other slightly better on average when ranking white American patients, but the
      overall differences were small. These findings appear consistent with the
      inference that, on average, judgments of "facial attractiveness" by orthodontists
      at the 2 venues are more similar than had been expected for patients of Chinese
      and white ethnicity.

PMID- 18617107
TI  - Evaluation of 3-dimensional tooth crown size in cleft lip and palate patients.
AB  - INTRODUCTION: The aims of this study were to evaluate 3-dimensional (3D) tooth
      crown sizes in patients with cleft lip and palate (CLP) and to compare them with
      those of a Class I control group. METHODS: Orthodontic dental casts were used of
      72 subjects with CLP (20 bilateral [BCLP], 34 unilateral left [ULCLP], 18
      unilateral right [URCLP]) and 53 adolescents in the permanent dentition stage
      with Class I occlusion. Mesiodistal (MD), labiolingual (LL), and occlusogingival
      (OG) measurements were recorded by the same examiner using a digital caliper.
      Statistical analyses were conducted, including repeatability, analysis of
      variance (ANOVA), and the Duncan tests. RESULTS: Maxillary and mandibular
      premolar MD dimensions were larger in the CLP groups than in the control group.
      The smallest MD dimensions were those of the maxillary right lateral incisors in
      the BCLP group (P <0.05). The maxillary left lateral incisor MD dimensions in the
      ULCLP group were smaller when compared with other CLP groups (P <0.001). In
      general, all LL and OG measurements were smaller in the CLP groups than in the
      Class I group in both dental arches. CONCLUSIONS: In general, MD, LL, and OG
      dimensions of CLP patients were smaller than those of the Class I subjects, not
      only in the affected maxillary dental arch, but also in the mandibular dental
      arch. Variations in 3D tooth dimensions were found among all CLP types. The
      lateral incisor in the cleft region was the smallest. A 3D tooth-size evaluation
      should be included in the diagnostic records to determine precise treatment
      planning and final occlusion in CLP patients.

PMID- 18617108
TI  - Effect of buccolingual root angulation on the mesiodistal angulation shown on
      panoramic radiographs.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effect of
      buccolingual root angulation on the perception of root parallelism in panoramic
      images. METHODS: A skull-typodont device was constructed according to
      cephalometric norms. The bases of the typodont were partially sectioned so that
      the buccolingual orientation of 4 adjacent pairs of teeth could be easily
      modified. Three buccolingual angulations were used for each tooth. Nine image
      sequences were necessary to analyze all possible buccolingual orientation
      combinations between adjacent teeth. The true root parallelism angulations
      relative to an orthodontic archwire were compared with the angulations obtained
      from scanned panoramic films. RESULTS: The largest root parallelism differences
      for adjacent teeth occurred between the maxillary canine and the first premolar.
      The second largest differences occurred in the mandibular canine-premolar area.
      No significant differences were found in the incisor area. CONCLUSIONS: The root
      parallelism expression in the canine-premolar region can be modified by altering
      the buccolingual orientation. Buccolingual orientation changes do not seem to
      affect the incisor area. The clinical usefulness of panoramic radiography to
      assess root parallelism should be approached with caution, especially in premolar
      extraction sites.

PMID- 18617109
TI  - Three-dimensional analysis system for orthognathic surgery patients with jaw
      deformities.
AB  - INTRODUCTION: Traditionally, lateral and frontal cephalograms are used with
      facial photographs to evaluate a patient's maxillofacial skeletal and facial soft
      tissue morphology. However, the enlargement and distortion of 2-dimensional
      radiography made it difficult to accurately conceptualize the patient's anatomy.
      The purpose of this article was to introduce a new method for comparing 3
      dimensional (3D) standard values of the maxillofacial skeletal and facial soft
      tissue morphology before and after orthognathic surgery. METHODS: Normative 3D
      standard values of the maxillofacial skeletal and facial soft-tissue morphology
      were calculated from normal women. The pre- and postoperative morphology of one
      woman who underwent orthognathic surgery was compared with the normative data.
      RESULTS: This 3D analysis has clinical value to evaluate patients before and
      after surgical treatment. CONCLUSIONS: This quantitative assessment of 3D
      maxillofacial morphology can evaluate the area and degree of displacement and
      rotation of the facial skeleton and facial soft tissues. This method is
      sufficiently useful for routine clinical applications.

PMID- 18617110
TI  - Three-dimensional accuracy of measurements made with software on cone-beam
      computed tomography images.
AB  - INTRODUCTION: The purpose of this article was to evaluate the accuracy of
      measurements made on 9- and 12-in cone-beam computed tomography (CBCT) images
      compared with measurements made on a coordinate measuring machine (CMM), which is
      the gold standard. METHODS: Ten markers were placed on a synthetic mandible, and
      landmark coordinates and linear and angular measurements were determined with the
      CMM. Three-dimensional CBCT images, measuring 9 and 12 in, were taken of the
      mandible with a CBCT machine (NewTom 3G, Aperio Services, Verona, Italy), and
      landmark coordinates and linear and angular measurements were obtained with AMIRA
      (Mercury Computer Systems, Berlin, Germany) software. RESULTS: The coordinate
      intrareliability correlation coefficient was almost perfect between the 3
      dimensional CBCT images and the CMM measurements. With the Student t test, we
      found no significant statistical difference between linear and angular
      measurements from the CMM and the NewTom 3G images, which differed less than 1 mm
      and 1 degrees , respectively. CONCLUSIONS: The NewTom 3G produces a 1-to-1 image
      to-reality ratio.

PMID- 18617111
TI  - Morphologic changes of the palate after rapid maxillary expansion: a 3
      dimensional computed tomography evaluation.
AB  - INTRODUCTION: The purpose of this retrospective study was to estimate the area
      change of the palate after rapid maxillary expansion (RME) in the early mixed
      dentition stage by using a 3-dimensional (3D) helical computed tomography (CT)
      scanning technique. In addition, linear changes in the maxillary arch were
      evaluated. METHODS: The treated sample consisted of 43 children (mean age, 9
      years 1 month) treated with a bonded RME appliance. The untreated control group
      consisted of 7 children (mean age, 9 years 3 months). Pretreatment and
      posttreatment dental casts were evaluated by using 3D helical CT scanning
      procedures. The Student t test was used to compare the linear, area, and angular
      differences between the treatment times. RESULTS: RME produced clinically
      significant increases in interdental widths across the canines, the deciduous
      first molars, and the permanent first molars in the maxillary arch. Significant
      increases in cross-sectional area were observed across the permanent first molars
      (15.3 mm(2)). There was marked variability in the buccal tipping of the permanent
      first molars. CONCLUSIONS: Three-dimensional helical CT scanning is an accurate
      and cost-effective method of assessing dental cast morphologic changes. It can
      also provide fast and accurate data acquisition and subsequent analysis.

PMID- 18617112
TI  - Longitudinal growth changes in untreated subjects with Class II Division 1
      malocclusion.
AB  - INTRODUCTION: The purpose of this longitudinal study was to compare the
      craniofacial growth changes in untreated subjects with Class II Division 1
      malocclusion with those in subjects with normal (Class I) occlusion from the
      prepubertal through the postpubertal stages of development, as defined by a
      biological indicator of individual skeletal maturity (cervical vertebral
      maturation method). METHODS: The Class II Division 1 sample consisted of 17
      subjects (11 boys, 6 girls). The Class I sample also consisted of 17 subjects (13
      boys, 4 girls). The lateral cephalograms of the subjects in both groups were
      analyzed at 6 consecutive stages of development, from CS1 through CS6. The
      statistical comparisons of the growth changes in the study groups were performed
      with Mann-Whitney U tests. RESULTS: Craniofacial growth in subjects with
      untreated Class II malocclusion is essentially similar to that in untreated
      subjects with normal occlusion at all developmental intervals, with the exception
      of significantly smaller increases in mandibular length (P <0.001) at the growth
      spurt (interval CS3-CS4) and during the overall observation period (intervals CS1
      CS6). CONCLUSIONS: Class II dentoskeletal disharmony does not tend to self
      correct with growth in association with worsening of the deficiency in total
      mandibular length and mandibular ramus height.

PMID- 18617113
TI  - Cephalometric findings in patients with Papillon-Lefevre syndrome.
AB  - INTRODUCTION: Literature regarding oral conditions in patients with Papillon
      Lefevre syndrome (PLS) often covers the periodontal aspects, but no literature
      was found describing specific craniofacial findings in this group. The aim of
      this retrospective study was to investigate the cephalometric findings of
      patients with PLS. METHODS: Lateral cephalograms of 8 patients with PLS were
      traced, and hard- and soft-tissue variables were analyzed. RESULTS: Class III
      skeletal relationship was evident (ANB angle, 2 degrees +/- 3.1 degrees ; Wits
      appraisal, -9.1 mm +/- 3.7 mm). Other findings include maxillary retrognathia,
      decreased lower facial height, retroclined mandibular incisors, and upper lip
      retrusion. CONCLUSIONS: Patients affected with PLS have a Class III skeletal
      pattern. These findings can be of clinical value not only for diagnosis, but also
      for proper treatment planning.

PMID- 18617114
TI  - Miniplates as skeletal anchorage for treating mandibular second molar impactions.
AB  - Mandibular second molar impactions can be difficult to correct and might require
      surgery. A young man with an impacted mandibular right second molar was treated
      with a miniplate, which provided anchorage to upright the tooth. Although other
      devices are available, this technique appears to be predictable and quick, and
      has few side effects.

PMID- 18617115
TI  - Nonsurgical management of a nonvital tooth with orthodontically induced external
      root resorption and extensive periapical pathology.
AB  - The purpose of this article is to report a rare case of orthodontically induced
      external root resorption of a maxillary left central incisor with a large
      periapical radiolucency; it was treated successfully with a conservative approach
      that included the use of calcium hydroxide. The tooth was nonvital and had grade
      III mobility. It was treated endodontically for 2 years with an interim filling
      of calcium hydroxide mixed with propylene glycol. After 2 years, the
      postoperative intraoral periapical radiograph showed good periapical healing with
      complete resolution of periapical radiolucency. There was a significant reduction
      in the mobility of the tooth, from grade III to grade I.

PMID- 18617116
TI  - Impaction and apical root angulation of the maxillary central incisors due to
      supernumerary teeth: combined surgical and orthodontic treatment.
AB  - This case report describes the treatment of a boy with both central maxillary
      incisors impacted because of 2 supernumerary teeth. Therapeutic management of the
      impacted teeth was combined with orthodontic treatment of a Class II Division 1
      malocclusion. A sequential approach of surgical removal of the supernumerary
      teeth with 2 stages of surgical exposure and orthodontic traction of the impacted
      teeth resulted in proper incisor positioning. Close monitoring and
      multidisciplinary cooperation during the various treatment phases led to a
      successful esthetic result, with good periodontal health and functional
      occlusion.

PMID- 18617117
TI  - Optimizing the design of preactivated titanium T-loop springs with Loop software.
AB  - A TMA (Ormco Corp, Glendora, Calif) T-loop spring (TTLS), preactivated with a
      gable bend distal to the loop, holds promise for producing controlled tipping of
      the canines and translation of the posterior segment. However, there is currently
      no consensus as to where the preactivated gable bend or the loop should be
      placed, what the height of the loop should be, or how the interbracket distance
      changes the moments produced. Using the Loop software program (dHal, Athens,
      Greece), we systematically modified a .017 x .025-in TTLS (10 x 6 mm) that was
      preactivated with a 45 degrees gable bend distal to the loop, and simulated the
      effects. As the gable bend was moved posteriorly, the moment increased at the
      posterior bracket more than it decreased at the anterior bracket. As the loop was
      brought closer to the anterior bracket, the posterior moment decreased at the
      same rate that it increased anteriorly. As the loop was increased in size, the
      moments increased both posteriorly and anteriorly. As the interbracket distance
      increased, the posterior moment decreased, and the anterior moment remained
      constant. We concluded that the size of the loop should be slightly increased, to
      10 x 7 mm, and it should be placed 2 mm from the anterior bracket, with a
      preactivation bend of 45 degrees , 4 to 5 mm from the posterior bracket (after 4
      mm of activation).

PMID- 18617118
TI  - Litigation, legislation, and ethics: duty defined.

PMID- 18617119
TI  - Etomidate infusion: a cause of hyperglycemia?

PMID- 18617120
TI  - Can ultrasound be useful for predicting the size of a left double-lumen bronchial
      tube? Tracheal width as measured by ultrasonography versus computed tomography.
AB  - STUDY OBJECTIVE: To correlate tracheal width as measured by ultrasound with width
      measured by computed tomography (CT), and to evaluate the possible role of
      ultrasound in the selection of the proper size of left-sided double-lumen
      endotracheal tubes (LDLTs). DESIGN: Two independent, prospective, observational
      clinical studies (Study 1 and Study 2). SETTING: University hospital. PATIENTS:
      Study 1 included 25 patients and Study 2 included 20 adult thoracic surgery
      patients who required a LDLT during anesthesia. INTERVENTIONS AND MEASUREMENTS:
      In Study 1, CT measurements of tracheal width were made at the coronary plane 0.5
      cm above the sternoclavicular joint; CT measurements of the left main bronchus
      diameter were made 1 cm below the carina. Ultrasound measurement of tracheal
      width was performed just above the sternoclavicular joint in the transversal
      section. In Study 2, patients' tracheas were intubated with a LDLT based on
      ultrasound measurements. The frequencies of incorrect selections of LDLT and
      unsatisfactory lung collapse were analyzed. MAIN RESULTS: There was a strong
      correlation between tracheal width as measured by ultrasound and tracheal width
      (r=0.882, P<0.001) and left main bronchus width (r=0.832, P<0.001) as measured by
      CT. In 5 cases (25%), the incorrect LDLT by ultrasound was selected; and one (5%)
      was found to have an unsatisfactory lung collapse. CONCLUSION: Measurement of the
      outer tracheal width by ultrasound can be a useful method for predicting the
      diameter of left main bronchus and for selecting a LDLT.

PMID- 18617121
TI  - Radial plus musculocutaneous nerve stimulation for axillary block is inferior to
      triple nerve stimulation with 2% mepivacaine.
AB  - STUDY OBJECTIVE: To compare the extent of sensory and motor block with two
      different nerve stimulation techniques in axillary blocks. DESIGN: Prospective,
      randomized, investigator-blinded study. SETTING: Ambulatory surgery unit of a
      university hospital. PATIENTS: 60 ASA physical status I, II, and III patients
      undergoing surgery at or below the elbow. INTERVENTIONS: Patients receiving
      axillary block were randomized into two nerve stimulation groups with either
      radial plus musculocutaneous or triple nerve stimulation (radial, median, and
      musculocutaneous nerves). Thirty milliliters of plain 2% mepivacaine was given to
      all patients either in a single or fractionated dosing for radial or for radial
      and median nerves, according to group assignment. Five milliliters of plain 1%
      mepivacaine for the musculocutaneous nerve was given to all patients.
      MEASUREMENTS: Blocks were assessed at 10, 20, and 30 minutes. Rates of
      supplementation given as a result of insufficient surgical anesthesia were also
      noted. MAIN RESULTS: Statistically significantly higher rates of anesthesia at
      the cutaneous distributions of median and medial cutaneous of the arm nerves with
      multiple nerve stimulation at 30 minutes were found as compared with radial plus
      musculocutaneous nerve stimulation. The rate of supplementation was lower with
      multiple nerve stimulation. CONCLUSIONS: Radial plus musculocutaneous nerve
      stimulation showed lower efficacy of axillary block than did triple nerve
      stimulation when using 2% mepivacaine.

PMID- 18617123
TI  - Who receives postoperative intensive and intermediate care?
AB  - STUDY OBJECTIVES: To examine the effects of preoperative and intraoperative
      factors that determine whether to provide postoperative intensive or intermediate
      care. DESIGN: Prospective observational study. SETTING: Tertiary-care university
      hospital. PATIENTS: 3,066 ASA physical status I, II, III, and IV adult patients,
      1,233 of whom were transferred to floor or the ambulatory surgery unit after a
      short postoperative recovery room stay (group 1), whereas the other 1,883 were
      admitted to intermediate and intensive care areas (group 2). INTERVENTIONS: None.
      MEASUREMENTS: Demographic and clinical information including preoperative medical
      history, extent of intraoperative care, and postoperative course were collected.
      Intraoperative activities were examined with the Operative Complexity Score and
      the Intraoperative Therapeutic Intensity Score. RESULTS: Almost all patients
      undergoing complex surgery (cardiac surgery and neurosurgery) received
      postoperative intermediate or intensive care, even if they had no significant
      underlying systemic diseases (ASA physical status I and II). Patients with severe
      underlying diseases (ASA physical status III and IV), but who underwent less
      extensive surgery, tended to receive intensive and intermediate care.
      Postoperative mechanical ventilation was associated with receipt of intensive
      rather than intermediate care. Interestingly, 10% of the elective surgery
      patients in group 2 unexpectedly received intensive or intermediate care because
      of intraoperative and immediate postoperative complications. CONCLUSIONS: Receipt
      of postoperative intermediate and intensive care is associated with distinct
      patterns of preoperative and intraoperative factors.

PMID- 18617122
TI  - Comparative effects of propofol, landiolol, and nicardipine on hemodynamic and
      bispectral index responses to endotracheal intubation: a prospective, randomized,
      double-blinded study.
AB  - STUDY OBJECTIVES: To examine the comparative effects of propofol, landiolol, and
      nicardipine on hemodynamic responses and bispectral index (BIS) changes to
      endotracheal intubation. SETTING: Operating room of a university-affiliated
      general hospital. PATIENTS: 27 ASA physical status I and II patients who were
      scheduled to undergo elective general surgical, urological, or gynecological
      procedures with general anesthesia. STUDY DESIGN: Prospective, randomized, double
      blinded study. INTERVENTIONS: Patients were divided into three groups as follows:
      Group 1 received propofol, 1 mg/kg; Group 2 received landiolol, 0.1 mg/kg; and
      Group 3 received nicardipine, 1 mg. After baseline measurements were recorded,
      anesthesia was induced with propofol, fentanyl, and vecuronium. Patients' lungs
      were ventilated with 100% oxygen for 120 seconds, at which time one of one of the
      study drugs was administered. Laryngoscopy and tracheal intubation were performed
      4 minutes after anesthetic induction. MEASUREMENTS: Cardiac index (CI) and stroke
      volume index (SVI) were monitored continuously. Bispectral index was also
      monitored continuously from 5 minutes after tracheal intubation. MAIN RESULTS:
      Heart rate values in Group 3 increased 30 seconds after intubation; this increase
      lasted for 1 minute after intubation. Systolic blood pressure in all three groups
      decreased after induction of anesthesia and before tracheal intubation, and
      values returned closer to baseline values 30 seconds after intubation. In the
      propofol group, CI and SVI decreased after administration of additional propofol,
      lasting for 30 seconds after intubation. The BIS values rapidly decreased after
      induction of anesthesia, with no intergroup differences noted in BIS values
      (propofol group, 39+/-7; landiolol group, 44+/-14; nicardipine group, 41+/-9).
      However, BIS was significantly lower in the propofol group than in the other two
      groups from 30 seconds to 5 minutes after intubation. CONCLUSIONS: Landiolol, 0.1
      mg/kg, before intubation provides effective hemodynamic stability in the
      postintubation period.

PMID- 18617124
TI  - The safety and efficacy of regional anesthesia in an office-based setting.
AB  - STUDY OBJECTIVE: To determine the safety and efficacy of regional anesthesia
      techniques when administered in the office-based setting. DESIGN: Retrospective
      chart review. SETTING: Free-standing orthopedic office with an operating room
      suite. MEASUREMENTS: A total of 238 patients underwent 242 anesthetics. Types of
      anesthetics delivered were quantified. Regional anesthetics were further divided
      into specific nerve blocks. Times from anesthetic start to surgical start and
      from surgical end to anesthetic end were calculated. Adverse outcomes were
      ascertained and followed. MAIN RESULTS: Of the 242 anesthetics administered, 123
      were peripheral nerve blocks, two were neuraxial blocks, 140 were monitored
      anesthesia care cases, and 17 were general anesthetics (14 Laryngeal Mask Airway
      cases, two mask ventilation cases, and one endotracheal intubation). The average
      times from anesthesia start to surgery start were as follows: monitored
      anesthesia cases, 19+/-7 min (median, 20 min); regional anesthesia cases, 29+/-11
      min (median, 30 min); and general anesthesia cases, 31+/-11 min (median, 30 min).
      The average time from surgery end to anesthesia end for monitored anesthesia
      cases was 9+/-3 min (median, 10 min); regional anesthesia, 9+/-3 min (median, 10
      min); and general anesthesia, 12+/-4 min (median, 20 min). Two transient nerve
      injuries occurred, both of which resolved. CONCLUSIONS: On the basis of our
      experience, we believe that regional anesthesia can be delivered efficiently and
      safely for orthopedic procedures in the office-based environment, and we
      encourage its wider use.

PMID- 18617125
TI  - Recombinant factor VIIa for warfarin-associated intracranial bleeding.
AB  - STUDY OBJECTIVE: To examine the efficacy of recombinant factor VIIa (rVIIa) in
      reversing warfarin-induced coagulopathy in trauma patients presenting with
      intracranial hemorrhage (ICH). DESIGN: Retrospective, cohort-controlled database
      review. SETTING: Level 1, university-affiliated trauma center. PATIENTS: 54
      patients presenting with ICH associated with chronic warfarin therapy, 30 of whom
      were treated with rVIIa, and the other 24 patients treated conventionally.
      MEASUREMENTS: We examined initial and subsequent coagulation studies (prothrombin
      time, international normalized ratio [INR]), blood product requirement, and
      clinical outcome, including time to reverse anticoagulation, duration of
      reversal, and subsequent mortality. MAIN RESULTS: Patients treated with rVIIa
      required significantly less plasma (4 vs 7 units) to correct their INR, and
      corrected in a much shorter period of time (2.4 vs 10 hrs). The duration of
      corrected INR after rVIIa was dose-dependent. CONCLUSIONS: Factor rVIIa provides
      prompt correction of the INR of dose-dependent duration in patients with ICH
      intracranial hemorrhage associated with warfarin use.

PMID- 18617126
TI  - Postoperative analgesia after total hip arthroplasty: patient-controlled
      analgesia versus transdermal fentanyl patch.
AB  - STUDY OBJECTIVE: To determine whether a new transdermal fentanyl patch (TFP) is a
      good choice for the postoperative pain management of patients undergoing primary
      total hip arthroplasty compared with patient-controlled analgesia (PCA). DESIGN:
      Randomized, prospective study. SETTING: University hospital. PATIENTS: 30
      patients undergoing primary total hip arthroplasty. INTERVENTIONS: Patients
      received either a TFP (group T; Duragesic 50 microg/h, matrix fentanyl patch,
      Janssen-Cilag) applied approximately 10 hours before induction of general
      anesthesia and PCA programmed in the postanesthesia care unit (PACU), or PCA
      programmed in the PACU (group P). MEASUREMENTS: Intraoperative sufentanil and
      additional postoperative morphine administration were recorded, as well as visual
      analog scores and routine vital signs at predetermined intervals during the first
      48 hours. MAIN RESULTS: Morphine consumption on arrival in the PACU was 3.5+/-3
      mg in group T versus 13+/-5 mg in group P (P<0.0001). Visual analog scores on
      arrival in the PACU were 37+/-22 mm in group T versus 73+/-13 mm in group P
      (P<0.0001). Cumulative morphine consumption at the 24th hour was 43+/-16 mg in
      group P and 4+/-3 mg in group T (P<0.0001). Cumulative morphine consumption at
      the 48th hour was 54+/-26 mg in group P and 5+/-4 mg in group T (P<0.0001).
      Intraoperative sufentanil consumption was 38+/-15 microg in group T versus 30+/-5
      microg in group P (not significant). The sedation score was 0 in both groups
      during the first 48 postoperative hours. CONCLUSIONS: Preoperative TFP
      application decreases pain scores and morphine consumption in the PACU and
      appears to have prolonged effects spanning the first 48 postoperative hours.

PMID- 18617127
TI  - The effect of metoprolol on perioperative outcome in coronary patients undergoing
      nonvascular abdominal surgery.
AB  - STUDY OBJECTIVE: To analyze the clinical effectiveness of the beta-1-adrenergic
      blocker, metoprolol. DESIGN: Prospective, observational, clinical study. SETTING:
      Operating room and intensive care unit of a tertiary-care teaching hospital.
      PATIENTS: 111 ASA physical status II, III, and IV consecutive patients who were
      scheduled for open abdominal nonvascular surgery. INTERVENTIONS: Patients were
      divided into two stratification groups: 83 (74.8%) of 111 received metoprolol,
      and 28 (25.2%) of 111 were controls. Within 24 to 96 hours, the drug was used
      parenterally in a dose of 5, 10, and 15 mg per 24 hours. Metoprolol
      cardioprotection was applied during the whole perioperative period, in the form
      of tablets in a dose of 25, 50, and 100 mg per 24 hours until the 30th
      postoperative day. MEASUREMENTS: During surgery, and in the first 72
      postoperative hours, patients were monitored by continuous ST-T segment
      monitoring. A 12-lead electrocardiogram was attached immediately after surgery;
      on postoperative days 1, 2, and 7; and one day before discharge from the
      hospital. Serum troponin-T level was controlled 6, 24, and 96 hours after
      surgery. MAIN RESULTS: Postoperative mortality of cardiac etiology after 30 days
      of surgery was 1.2% (1/83) in the metoprolol group versus 7.1% (2/28) in the
      nonmetoprolol group (P<0.05). The causes of death in these three patients were
      acute myocardial infarction, congestive heart failure, and malignant arrhythmias.
      CONCLUSIONS: Perioperative cardioprotection significantly reduced mortality until
      postoperative day 30 in patients having open abdominal nonvascular surgery with
      general anesthesia.

PMID- 18617128
TI  - Hyperosmolar, increased-anion-gap metabolic acidosis and hyperglycemia after
      etomidate infusion.
AB  - Hyperosmolar increased-anion-gap metabolic acidosis without hyperglycemia has
      been reported after infusions of etomidate and other medications containing
      propylene glycol. We report a case of this biochemical abnormality with severe
      hyperglycemia. Cessation of the etomidate infusion along with other supportive
      measures resulted in prompt resolution of the metabolic acidosis and
      hyperglycemia.

PMID- 18617129
TI  - Successful resuscitation of a patient who developed cardiac arrest from pulsed
      saline bacitracin lavage during thoracic laminectomy and fusion.
AB  - A patient with a history of T12 burst fracture caused by a fall, and with
      progressive weakness and sensory loss in the left leg, survived a cardiac arrest
      after pulsed saline bacitracin lavage irrigation during a posterior spinal
      fusion.

PMID- 18617130
TI  - The use of continuous positive airway pressure during an awake craniotomy in a
      patient with obstructive sleep apnea.
AB  - We describe the anesthetic management of a morbidly obese patient with
      obstructive sleep apnea who underwent awake craniotomy. The patient's personal
      continuous positive airway pressure (CPAP) machine was used to support
      ventilation intraoperatively. Dexmedetomidine was used as the primary sedative.
      During cortical mapping, the CPAP was discontinued. The patient was comfortable
      and able to cooperate with language testing.

PMID- 18617131
TI  - Morphine-induced acute lung injury.
AB  - A 38-year-old woman who had familial adenomatous polyposis was admitted to the
      intensive care unit with an episode of severe sepsis 5 days after undergoing a
      pancreas-preserving duodenectomy. Laparotomy with removal of an intra-abdominal
      abscess, followed by closed postoperative continuous lavage for 10 days, was
      performed. During two courses of planned tracheal extubation, the patient
      developed an acute lung injury, making a reintubation necessary. In both events,
      the patient received small doses of continuous morphine before the extubation.
      Morphine may induce the development of an acute lung injury in patients, whereas
      the exact pathophysiologic and pharmacologic mechanisms remain unclear.

PMID- 18617132
TI  - Horner's syndrome secondary to internal jugular venous cannulation.
AB  - Horner's syndrome is a rare complication following insertion of a central
      catheter into the internal jugular vein (IJV). A 5-year-old boy, who developed
      unilateral Horner's syndrome postoperatively following IJV cannulation, is
      presented. The Horner's syndrome resolved completely after 5 months.

PMID- 18617133
TI  - Perioperative spinal cord infarction in nonaortic surgery: report of three cases
      and review of the literature.
AB  - Paraplegia caused by a spinal cord infarction (SCI) is a devastating
      perioperative complication, most often associated with aortic and spine surgery.
      We present two other clinical scenarios in which perioperative SCI may occur.
      They happened during surgical procedures performed with epidural anesthesia, in
      the presence of several specific risk factors such as spinal stenosis, vascular
      disease, intraoperative hypotension, or the use of epinephrine in the local
      anesthetic solution. Second, SCI may occur during episodes of postoperative
      hypotension in patients with a history of aortic aneurysms.

PMID- 18617134
TI  - Nonmalignant hyperthermia and malignant hyperthermia confused.

PMID- 18617135
TI  - Malignant hyperthermia or malignant hyperthermia-like syndrome.

PMID- 18617137
TI  - Trauma airway salvage using an optical stylet with oxygen insufflation.

PMID- 18617138
TI  - The Airway Scope for difficult double-lumen tube intubation.

PMID- 18617139
TI  - Preliminary evaluation of a novel videolaryngoscope, the McGrath series 5, in the
      management of difficult and challenging endotracheal intubation.

PMID- 18617140
TI  - Fiberoptic-guided intubation via the Laryngeal Mask Airway Supreme.

PMID- 18617141
TI  - Metabolic and proteomic study of NS0 myeloma cell line following the adaptation
      to protein-free medium.
AB  - Proteomics and metabolomics technologies are potentially useful tool for the
      study of the very complex process of cell adaptation to protein-free medium. In
      this work, we used the iTRAQ technology to analyze different protein levels in
      adapted and non-adapted NS0 myeloma cell line. Several proteins with differential
      expression profile were characterized and quantified. Carbohydrate metabolism,
      protein synthesis and membrane transport were the principal pathways that change
      after the adaptation. Changes in lactate production rate with respect to glucose
      consumption rate were observed according to the changes observed by proteomic.

PMID- 18617142
TI  - The effect of the bacterial effector protein harpin on transcriptional profile
      and mitochondrial proteins of Arabidopsis thaliana.
AB  - Here we report on the effect of the bacterial elicitor harpin from Pseudomonas
      syringae on Arabidopsis thaliana with an emphasis on transcriptional profiling
      and on changes of the mitochondrial proteome. Interestingly, of the currently
      about 400 identified mitochondrial proteins, transcriptional profiling by genome
      wide DNA-microarray analyses revealed a total of 192 genes that showed
      significant changes in transcript abundance in response to the bacterial
      elicitor. The most dramatic changes were observed for the mitochondrial protein
      import apparatus of which 70% of all genes were induced. Proteomic analyses by 2D
      PAGE and MALDI-TOF Mass Spectrometry for peptide fingerprint analysis confirmed
      the corresponding changes within the mitochondrial proteome in 28 cases.
      Strikingly, we found an accumulation of virtually all members of the TCA cycle.
      In sum, our results point to an involvement of mitochondria in the response of
      plant cells to the harpin elicitor, which becomes apparent both at the
      transcriptomic as well as proteomic level.

PMID- 18617143
TI  - Assessing CMT cell line stability by two dimensional polyacrylamide gel
      electrophoresis and mass spectrometry based proteome analysis.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by mass
      spectrometric identification of the proteins in the protein spots has become a
      central tool in proteomics. CMT167(H), CMT64(M) and CMT170(L) cell lines,
      selected from a spontaneous mouse lung adenocarcinoma, with high-, middle- or low
      metastatic potential have been characterized in vivo. In this study, the
      comprehensive protein expression profiles of the CMT cell lines were analyzed at
      passages 5, 15 and 35 in order to assess the cell line stability. During the
      passages 5 to 15, the expression profiles of CMT cells remained reasonably stable
      as evidenced by only 0.7%, 3.9% and 1.1% proteins changed in CMT167(H), CMT64(M)
      and CMT170(L) respectively. However, the number of differentially expressed
      proteins were considerably increased at passage 35 in CMT64(M) and CMT170(L)
      while CMT167(H) remained stable. Based on our selection criteria, 22, 109 and 84
      spots in CMT167(H), CMT64(M) and CMT170(L) were selected for protein
      identification by MS and 99 unique proteins were identified. Bioinformatics
      analysis indicated that most of these proteins participate in cellular
      metabolism. In conclusion, proteomics was found to be a useful tool for assessing
      differences in cell line stability. This approach provided a tool to select the
      best cell line and optimal subculture period for studies of cancer related
      phenomena and for testing the effect of potential anticancer drugs.

PMID- 18617144
TI  - Analysis of the saliva proteome from patients with head and neck squamous cell
      carcinoma reveals differences in abundance levels of proteins associated with
      tumour progression and metastasis.
AB  - The objective of this study was to identify differentially expressed proteins in
      saliva from HNSCC patients compared to a control group. Saliva samples from eight
      individuals with non-malignant conditions of the head and neck region were
      employed as a control group and compared to saliva from eight patients with HNSCC
      using 2D DIGE analysis and subsequent mass spectrometry identification of
      candidate proteins. Beta fibrin (+2.77-fold), S100 calcium binding protein (+5.35
      fold), transferrin (+3.37-fold), immunoglobulin heavy chain constant region gamma
      (+3.28) and cofilin-1 (+6.42) were all found to be significantly increased in the
      saliva from HNSCC samples compared to the control group whereas transthyretin (
      2.92-fold) was significantly decreased. The increased abundance of one of the
      proteins identified (S100 calcium binding protein) was confirmed by immunoblot
      analysis. Many of these proteins are involved in tumour progression, metastasis
      and angiogenesis. The proximity of saliva to the developing tumour is undoubtedly
      a major factor in facilitating detection of these proteins and such a strategy
      may lead to the development of a panel of biomarkers useful for therapeutic
      monitoring and for early detection of HNSCC.

PMID- 18617145
TI  - The expression of tomato prosystemin gene in tobacco plants highly affects host
      proteomic repertoire.
AB  - Systemin, an octadecapeptide isolated from tomato, is a primary signal molecule
      involved in the local and systemic responses to pest attack, elicited by
      activation of a set of defence genes. It derives from processing of prosystemin,
      a prohormone of almost 200 amino acids. Prosystemin orthologues have been found
      in other Solanaceae species but not in tobacco, where are present hydroxyproline
      rich peptides functionally but not structurally related to tomato systemin.
      Molecular events leading to the release of signalling peptides from protein
      precursors are unknown in plants; the occurrence of a family of signal molecules
      suggests that initiation of wound response may involve different processing
      mechanisms. It has been previously shown that the protein product from an
      engineered tomato prosystemin gene is processed in tobacco, thus suggesting that
      the components responsible for its post-translational modifications are present
      in this species. By analyzing analysing the proteome repertoire of transformed
      tobacco plant leaves with 2-DE, here we demonstrate that the constitutive
      expression of the tomato prosystemin gene highly affected host protein synthesis.
      In particular, engineered plants showed a number of differentially synthesized
      proteins that were identified by PMF MALDI-TOF and microLC-ESI-IT-MS/MS
      experiments as polypeptide species involved in protection from pathogens and
      oxidative stress, or in carbon/energy metabolism. Significant differences in over
      produced proteins were observed with respect to previous data reported on
      systemin-engineered tomato plants. Our results strongly support the need of using
      proteomic approaches during systematic analysis of plant tissues to investigate
      the principle of substantial equivalence in transgenic plants expressing a
      transgene coding for a signalling molecule.

PMID- 18617146
TI  - Mass spectrometric and linear discriminant analysis of N-glycans of human serum
      alpha-1-acid glycoprotein in cancer patients and healthy individuals.
AB  - N-glycan oligosaccharides of human serum alpha(1)-acid glycoprotein (AGP) samples
      isolated from 43 individuals (healthy individuals and patients with lymphoma and
      with ovarian tumor) were analyzed by MALDI-TOF mass spectrometry and a
      multivariate statistical method (linear discriminant analysis, LDA). 34 different
      glycan structures have been identified. From the glycosylation pattern determined
      by mass spectrometry fucosylation and branching indices have been calculated.
      These parameters show only small differences between the patient groups studied,
      but these differences are not sufficiently large to use as a potential biomarker.
      LDA analysis, on the other hand shows a very good separation between the three
      groups (with a classification of 88%). Cross-validation indicates that the method
      has predictive power: Identifying cancerous vs. healthy individuals shows 96%
      selectivity and 93% specificity; identification of lymphoma vs. the mixed group
      of healthy and ovarian tumor cases is also promising (72% selectivity and 84%
      specificity). The pilot study presented here demonstrates that mass spectrometry
      combined with linear discriminant analysis (LDA) may provide valuable data for
      identifying and studying the pathophysiology of malignant diseases.

PMID- 18617147
TI  - Proteomic analysis of exhaled breath condensate from single patients with
      pulmonary emphysema associated to alpha1-antitrypsin deficiency.
AB  - The non-invasive character of exhaled breath (EBC) collection makes this fluid
      attractive for monitoring the respiratory tract by the measurement of various
      compounds. Because EBC is likely to reflect the composition of the airway-lining
      fluid, it can provide valuable information on possible disease states. Aim of our
      study was to apply proteomic technology to the study of EBC samples collected
      from single patients with pulmonary emphysema associated to alpha(1)-antitrypsin
      deficiency. The protein profiles from EBC of twenty patients and of twenty-five
      healthy individuals, used as controls, have been analyzed in parallel by a
      combination of 1-DE, 2-DE, micro-HPLC and MS. These sensitive techniques allowed
      to identify a number of cytokines and cytokeratins. Their level was found to be
      higher in patients than in controls.

PMID- 18617148
TI  - The World-2DPAGE Constellation to promote and publish gel-based proteomics data
      through the ExPASy server.
AB  - Since it was launched in 1993, the ExPASy server has been and is still a
      reference in the proteomics world. ExPASy users access various databases, many
      dedicated tools, and lists of resources, among other services. A significant part
      of resources available is devoted to two-dimensional electrophoresis data. Our
      latest contribution to the expansion of the pool of on-line proteomics data is
      the World-2DPAGE Constellation, accessible at http://world-2dpage.expasy.org/. It
      is composed of the established WORLD-2DPAGE List of 2-D PAGE database servers,
      the World-2DPAGE Portal that queries simultaneously world-wide proteomics
      databases, and the recently created World-2DPAGE Repository. The latter component
      is a public standards-compliant repository for gel-based proteomics data linked
      to protein identifications published in the literature. It has been set up using
      the Make2D-DB package, a software tool that helps building SWISS-2DPAGE-like
      databases on one's own Web site. The lack of necessary informatics infrastructure
      to build and run a dedicated website is no longer an obstacle to make proteomics
      data publicly accessible on the Internet.

PMID- 18617154
TI  - Dissociating congruence effects in letters versus shapes: Kanji and kana.
AB  - In order to consolidate the dissociation in feature integration found in earlier
      studies between letters of the Roman alphabet and corresponding pseudo-letters,
      the present study used kanji and kana and corresponding pseudo-letters, presented
      visually, either in isolation or surrounded by congruent or incongruent shape, as
      targets in a choice-response task with three different response criteria. When
      the criterion was shape, congruence effects were obtained for both real and
      pseudo-letters. With the second and third response criteria this result was found
      for pseudo-letters, but not for letters. These criteria either involved
      distinguishing between letters and visually similar pseudo-letters or
      distinguishing between visually similar letters. The dissociation of congruence
      effects between letters and pseudo-letters was therefore shown to depend on
      visual similarity between targets, independent of their category. This effect was
      found to be robust for kanji but not for kana, which is related to distinctions
      between these two writing systems.

PMID- 18617155
TI  - Clinical therapy of schistosomiasis mansoni: the Brazilian contribution.
AB  - The review gives a detailed account of the history of drug development, treatment
      and drug resistance for clinical therapy of schistosomiasis mansoni, specially
      emphasizing the importance of Brazilian contribution on antischistosomal
      chemotherapy, as well as on the control of this parasitic disease.

PMID- 18617156
TI  - Carbachol-induced in vitro secretion of certain human submandibular proteins
      investigated by mass-spectrometry.
AB  - OBJECTIVE: To investigate protein content of saliva produced in vitro by samples
      of human submandibular gland following stimulation with the muscarinic agent
      carbachol. DESIGN: Tissue samples, obtained at surgery from seven patients and
      showing normal morphological appearance, were tested for 30 min: in absence of
      carbachol and atropine; in presence of carbachol (10 microM); in presence of
      carbachol (10 microM) and atropine (20 microM); or in presence of just atropine
      (20 microM). Medium was analysed by high-performance liquid chromatography-mass
      spectrometry. Neither before nor during surgery were the patients exposed to drug
      treatments that were likely to influence the in vitro secretion. RESULTS: Proline
      rich proteins (PRP)-1 and -3, peptide PC and PB, statherin, cystatins SN, S1 and
      S2 were invariably found in control gland tissue medium. Mean concentrations of
      these proteins/peptides in the medium were non-proportionally elevated following
      carbachol exposure to the gland tissues. Difference between basal release and
      carbachol-induced secretion achieved statistical significance as to all the
      proteins/peptides under study but for statherin. Atropine alone or atropine plus
      carbachol caused no significant changes compared to the basal release of
      proteins/peptides. CONCLUSIONS: In vitro studies on salivary glands make it
      possible to study protein secretion from individual glands and thus, to reveal
      the contribution of the various types of gland to protein/peptide content of
      whole saliva. The disproportional responses to carbachol may imply that the
      proteins/peptides are not confined to the same cells or to the same intracellular
      locations and are therefore not secreted as packages at parasympathetic
      cholinergic activity.

PMID- 18617157
TI  - Erlotinib and gefitinib for the treatment of myelodysplastic syndrome and acute
      myeloid leukemia: a preclinical comparison.
AB  - Erlotinib and gefitinib, two inhibitors of the epidermal growth factor receptor
      (EGFR), can stimulate apoptosis and differentiation of myeloid cell lines that
      lack EGFR, unveiling a novel, therapeutically exploitable off-target effect of
      tyrosine kinase inhibitors. Here, we performed a side-by-side comparison of
      erlotinib and gefitinib effects on a broad spectrum of malignant myeloid cell
      lines, as well as on primary myeloblasts freshly purified from the bone marrow of
      patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
      Both erlotinib and gefitinib induce apoptosis of a cell line (KG-1) that
      represents AML, and differentiation in another cell line (P39) derived from a
      patient with high-risk MDS. In this setting, erlotinib was more efficient than
      gefitinib. Erlotinib and gefitinib were equipotent in inducing apoptosis of
      primary CD34+ myeloblasts from MDS and AML patients, yet had no toxic effect on
      CD34+ progenitor cells from healthy donors. Although the response of individual
      MDS and AML patients in vitro was highly heterogeneous, the pro-apoptotic effects
      of erlotinib and gefitinib correlated significantly. These results suggest that
      erlotinib and gefitinib share a mechanistically related off-target effect that
      may be taken advantage of for the therapy of MDS and AML.

PMID- 18617158
TI  - Human and animal sounds influence recognition of body language.
AB  - In naturalistic settings emotional events have multiple correlates and are
      simultaneously perceived by several sensory systems. Recent studies have shown
      that recognition of facial expressions is biased towards the emotion expressed by
      a simultaneously presented emotional expression in the voice even if attention is
      directed to the face only. So far, no study examined whether this phenomenon also
      applies to whole body expressions, although there is no obvious reason why this
      crossmodal influence would be specific for faces. Here we investigated whether
      perception of emotions expressed in whole body movements is influenced by
      affective information provided by human and by animal vocalizations. Participants
      were instructed to attend to the action displayed by the body and to categorize
      the expressed emotion. The results indicate that recognition of body language is
      biased towards the emotion expressed by the simultaneously presented auditory
      information, whether it consist of human or of animal sounds. Our results show
      that a crossmodal influence from auditory to visual emotional information obtains
      for whole body video images with the facial expression blanked and includes human
      as well as animal sounds.

PMID- 18617159
TI  - The inferior frontal cortex in artificial syntax processing: an rTMS study.
AB  - The human capacity to implicitly acquire knowledge of structured sequences has
      recently been investigated in artificial grammar learning using functional
      magnetic resonance imaging. It was found that the left inferior frontal cortex
      (IFC; Brodmann's area (BA) 44/45) was related to classification performance. The
      objective of this study was to investigate whether the IFC (BA 44/45) is causally
      related to classification of artificial syntactic structures by means of an off
      line repetitive transcranial magnetic stimulation (rTMS) paradigm. We manipulated
      the stimulus material in a 2 x 2 factorial design with grammaticality status and
      local substring familiarity as factors. The participants showed a reliable effect
      of grammaticality on classification of novel items after 5 days of exposure to
      grammatical exemplars without performance feedback in an implicit acquisition
      task. The results show that rTMS of BA 44/45 improves syntactic classification
      performance by increasing the rejection rate of non-grammatical items and by
      shortening reaction times of correct rejections specifically after left-sided
      stimulation. A similar pattern of results is observed in FMRI experiments on
      artificial syntactic classification. These results suggest that activity in the
      inferior frontal region is causally related to artificial syntax processing.

PMID- 18617160
TI  - The effects of pattern shape, subliminal stimulation, and voluntary control on
      multistable visual perception.
AB  - Spontaneous figure reversal of ambiguous patterns was analyzed in humans. A) With
      Necker-"cube"-like, or "drum"-like figures, having square or round shaped "front"
      and "rear" surfaces, and either large or small "depth", the perceptual intervals
      corresponding to both interpretations of "drum" were longer than those of "cube";
      the perceived "depth" of the figures was less relevant for reversal timing (inter
      reversal intervals were only slightly longer for the "deeper" figures). Although
      the shape of "front" and "rear" surfaces is not a crucial geometrical feature for
      figure reversal, it did influence its timing. More, or longer information
      processing steps should probably be needed for perceptual representations of
      curvilinear patterns in comparison with rectangular ones. The underlying neural
      mechanisms are probably located at a relatively peripheral level in the visual
      system. B) With a modified Necker "cube"-like figure, having the two internal
      vertices coincident, and the long axis of the figure aligned horizontally, the
      effect of voluntary control on perception-reversal timing overcomes opposite
      effects due to either fixation-attention to pattern's focal zones, or subliminal
      stimulation by the pattern's biased versions, suggesting one or the other
      perception's possibility, while it is enhanced by concordant imagery. Voluntary
      control should intervene downward at a high-level processing, and should probably
      affect both a decision-making and a perception-stabilizing mechanism in the
      process of the pattern's unconscious interpretation. Results A and B are
      confronted with other results on both perceptual and binocular rivalry of up-to
      date literature, in the frame of discussions on low-level bottom-up automatic
      stimulus-driven processing vs high-level top-down covert attention-driven
      processing.

PMID- 18617161
TI  - Potency of several oximes to reactivate human acetylcholinesterase and
      butyrylcholinesterase inhibited by paraoxon in vitro.
AB  - Organophosphorus pesticides (e.g. chlorpyrifos, malathion, and parathion) and
      nerve agents (sarin, tabun, and VX) are highly toxic organophosphorus compounds
      with strong inhibition potency against two key enzymes in the human body
      acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BuChE; EC
      3.1.1.8). Subsequent accumulation of acetylcholine at synaptic clefts can result
      in cholinergic crisis and possible death of intoxicated organism. For the
      recovery of inhibited AChE, derivatives from the group of pyridinium or
      bispyridinium aldoximes (called oximes) are used. Their efficacy depends on their
      chemical structure and also type of organophosphorus inhibitor. In this study, we
      have tested potency of selected cholinesterase reactivators (pralidoxime,
      obidoxime, trimedoxime, methoxime and H-oxime HI-6) to reactivate human
      erythrocyte AChE and human plasma BuChE inhibited by pesticide paraoxon. For this
      purpose, modified Ellman's method was used and two different concentrations of
      oximes (10 and 100 microM), attainable in the plasma within antidotal treatment
      of pesticide intoxication were tested. Results demonstrated that obidoxime
      (96.8%) and trimedoxime (86%) only reached sufficient reactivation efficacy in
      case of paraoxon-inhibited AChE. Other oximes evaluated did not surpassed more
      than 25% of reactivation. In the case of BuChE reactivation, none of tested
      oximes surpassed 12.5% of reactivation. The highest reactivation efficacy was
      achieved for trimedoxime (12.4%) at the concentration 100 microM. From the data
      obtained, it is clear that only two from currently available oximes (obidoxime
      and trimedoxime) are good reactivators of paraoxon-inhibited AChE. In the case of
      BuChE, none of these reactivators could be used for its reactivation.

PMID- 18617162
TI  - Extracellular regulation of developmental cell signaling by XtSulf1.
AB  - Heparan sulfate proteoglycans (HSPGs) are synthesised and modified in the Golgi
      before they are presented at the cell surface. Modifications include the addition
      of sulfate groups at specific positions on sugar residues along the heparan
      sulfate (HS) chain which results in a structural heterogeneity that underpins the
      ability of HSPGs to bind with high affinity to many different proteins, including
      growth factors and their receptors. Sulf1 codes for a 6-0-endosulfatase that is
      present and active extracellularly, providing a further mechanism to generate
      structural diversity through the post-synthetic remodelling of HS. Here we use
      Xenopus embryos to demonstrate in vivo that Xtsulf1 plays an important role in
      modulating cell signaling during development. We show that while XtSulf1 can
      enhance the axis-inducing activity of Wnt11, XtSulf1 acts during embryogenesis to
      restrict BMP and FGF signaling.

PMID- 18617163
TI  - Molecular and functional mapping of regional differences in P2Y receptor
      expression in the rat lens.
AB  - Extracellular ATP has been shown to mobilize intracellular Ca(2+) in cultured
      ovine lens epithelial cells and in human lens epithelium, suggesting a role for
      purines in the modulation of lens transparency. In this study, we characterized
      the expression profiles of P2Y receptor isoforms throughout the rat lens at both
      the molecular and the functional levels. RT-PCR indicated that P2Y(1), P2Y(2),
      P2Y(4) and P2Y(6) are expressed in the lens, while P2Y(12), P2Y(13) and P2Y(14)
      are not. Immunohistochemistry, using isoform specific antibodies, indicated that
      the epithelium does not express P2Y(1) and P2Y(2), but that the underlying fiber
      cells, which differentiate from the epithelial cells, exhibit strong membranous
      labeling. Although co-expressed in fiber cells, differences in P2Y(1) and P2Y(2)
      expression were apparent. P2Y(1) expression extended deeper into the lens than
      P2Y(2), and its expression co-localized with Cx50 gap junction plaques, while
      P2Y(2) did not. Labeling for P2Y(4) and P2Y(6) receptors were observed in both
      epithelial cells and fiber cells, but the labeling was predominantly cytoplasmic
      in nature. While purine agonist (ATP, ADP, UTP and UDP) application to the lens
      induced mobilization of intracellular Ca(2+) in cortical fiber cells, little to
      no effect was observed in the anterior and equatorial epithelium. Thus the
      inability of UTP and UDP to mobilize intracellular Ca(2+) in the epithelium and
      the predominately cytoplasmic location of P2Y(4) and P2Y(6) suggests that these
      receptors may represent an inactive pool of receptors that may be activated under
      non-physiological conditions. In contrast, our results indicated that P2Y(1) and
      P2Y(2) are functionally active in fiber cells and their differential subcellular
      expression patterns suggest they may regulate distinct processes in the lens
      under steady state conditions.

PMID- 18617164
TI  - Ultrastructural analysis of damage to nuclear fiber cell membranes in advanced
      age-related cataracts from India.
AB  - The primary goal was to characterize the structural alterations that occur at the
      fiber cell interfaces in nuclei of fully opaque cataracts removed by
      extracapsular cataract surgery in India. The dark yellow to brunescent nuclei,
      ages 38-78 years, were probably representative of advanced age-related nuclear
      cataracts. Thick tissue slices were fixed, en bloc stained and embedded for
      transmission electron microscopy. Stained thin sections contained well-preserved
      membranes and junctions, although the complex cellular topology often made it
      necessary to tilt the grid extensively to visualize the membranes. Damage to the
      fiber cell membranes was noted in all regions of the nucleus. The most important
      damage occurred within undulating membrane junctions where the loss of membrane
      segments was common. These membrane breaks were not sites of fusion as membrane
      edges were detected and cytoplasm appeared to be in contact with extracellular
      space, which was enlarged in many regions. Dense deposits of protein-like
      material were frequently observed within the extracellular space and appeared to
      be similar to protein in the adjacent cytoplasm. The deposits were often 20-50 nm
      thick, variable in length and located on specific sites on plasma membranes and
      between clusters of cells or cell processes. In addition, low density regions
      were seen within the extracellular space, especially within highly undulating
      membranes where spaces about 100 nm in diameter were observed. The membrane
      damage was more extensive and extracellular spaces were larger than in aged
      transparent donor lenses. Because high and low density regions contribute equally
      to the fluctuations in refractive index, the changes in density due to the
      observed damage near membranes are likely to produce significant light scattering
      based on theoretical analysis. The dimensions of the fluctuations in the range 20
      100 nm imply that the scattering is probably similar to that of small particles
      that would increase high-angle scattering visible in the slit lamp. Such damage
      to membranes would be expected to contribute to the total opacification of the
      nucleus as the cataract matures. The main sources of the fluctuations appear to
      be the degradation of membranes and adjacent cytoplasmic proteins, as well as the
      redistribution of proteins and fragments.

PMID- 18617166
TI  - Ammonium tetrathiomolybdate delays onset, prolongs survival, and slows
      progression of disease in a mouse model for amyotrophic lateral sclerosis.
AB  - Mutations in copper/zinc superoxide dismutase (SOD1) cause a form of familial
      amyotrophic lateral sclerosis (ALS). The pathogenesis of familial ALS may be
      associated with aberrant copper chemistry through a cysteine residue in mutant
      SOD1. Ammonium tetrathiomolybdate (TTM) is a copper-chelating drug that is
      capable of removing a copper ion from copper-thiolate clusters, such as SOD1. We
      found that TTM exerted therapeutic benefits in a mouse model of familial ALS
      (SOD1(G93A)). TTM treatment significantly delayed disease onset, slowed disease
      progression and prolonged survival by approximately 20%, 42% and 25%,
      respectively. TTM also effectively depressed the spinal copper ion level and
      inhibited lipid peroxidation, with a significant suppression of SOD1 enzymatic
      activity in SOD1(G93A). These results support the hypothesis that aberrant copper
      chemistry through a cysteine residue plays a critical role in mutant SOD1
      toxicity and that TTM may be a promising therapy for familial ALS with SOD1
      mutants.

PMID- 18617165
TI  - Living or dying in three quarter time: neonatal orchestration of hippocampal cell
      death pathways by androgens and excitatory GABA.

PMID- 18617167
TI  - Leishmania donovani pteridine reductase 1: biochemical properties and structure
      modeling studies.
AB  - Pteridine reductase 1 (PTR1, EC 1.5.1.33) is a NADPH dependent short-chain
      reductase (SDR) responsible for the salvage of pterins in the protozoan parasite
      Leishmania. This enzyme acts as a metabolic bypass for drugs targeting
      dihydrofolate reductase, therefore, for successful antifolate chemotherapy to be
      developed against Leishmania, it must target both enzyme activities. Based on
      homology model drawn on recombinant pteridine reductase isolated from a clinical
      isolate of L. donovani, we carried out molecular modeling and docking studies
      with two compounds of dihydrofolate reductase specificity showing promising
      antileishmanial activity in vitro. Both the inhibitors appeared to fit well in
      the active pocket revealing the tight binding of the carboxylic acid ethyl ester
      group of pyridine moiety to pteridine reductase and identify the important
      interactions necessary to assist the structure based development of novel
      pteridine reductase inhibitors.

PMID- 18617168
TI  - Pelvic fractures due to falls from a height in people with mental disorders.
AB  - BACKGROUND: Pelvic fracture resulting from a fall, is a serious condition with
      morbidity and mortality that are higher among people with mental disorders.
      METHODS: A retrospective study of fall pelvic fractures 1999-2006, comparing
      clinical features of cases with and without mental disorders. RESULTS: Of 248
      participants, 69 had comorbid mental disorder, sustained worse injuries requiring
      more treatment, and displayed injury recidivism. CONCLUSION: A strategy of injury
      prevention is vital in the subsequent management of these patients.

PMID- 18617169
TI  - Factors predicting patient satisfaction following major trauma.

PMID- 18617170
TI  - Innovations in osteosynthesis and fracture care.
AB  - Over the years giant steps have been made in the evolution of fracture fixation
      and the overall clinical care of patients. Better understanding of the
      physiological response to injury, bone biology, biomechanics and implants has led
      to early mobilisation of patients. A significant reduction in complications
      during the pre-operative and post-operative phases has also been observed,
      producing better functional results. A number of innovations have contributed to
      these improved outcomes and this article reports on the advances made in
      osteosynthesis and fracture care.

PMID- 18617171
TI  - Acute postpartum aortic dissection.

PMID- 18617172
TI  - Putting sexual and reproductive health on the agenda.

PMID- 18617173
TI  - The role of qualitative research within an evidence-based context: can
      metasynthesis be the answer?
AB  - The increasing emphasis on evidence in the health care planning and policy
      context has fuelled considerable discussion and debate in nursing circles on the
      appropriate place of the less favourably placed knowledge forms within the
      conventional evidentiary hierarchy. In this paper, nursing's affinity for
      qualitative methods, and the species of knowledge they generate, are considered
      within the context of this evolving evidence-based practice movement. Noting
      conceptual and terminological confusions around the notion of evidence such as
      have arisen within the nursing literature, the author argues for clarity in our
      collective thinking about the role of research in a nursing or any other applied
      practice discipline. Toward this end, she points to some of the newer approaches
      to research synthesis and integration that may hold particular promise for
      enhancing our confidence about what might properly constitute a qualitatively
      derived evidentiary knowledge claim. Such approaches may assist nurses to work
      more comfortably within the evidence-based movement, assured that reliance upon
      scientifically sound reference points need not compromise the complexity,
      richness and diversity they recognize as inherent in practice context excellence.

PMID- 18617174
TI  - The Nuclear Factor-kappa B p50 subunit is involved in flow-induced outward
      arterial remodeling.
AB  - AIMS: Outward arterial remodeling is a structural enlargement of the artery that
      is associated with unstable inflammatory atherosclerotic lesions. Toll-like
      receptor (Tlr) activation is known as a key pathway in outward arterial
      remodeling. Tlr activation results in nuclear translocation of the transcription
      factor Nuclear Factor-kappa B (NF-kappaB) that controls the transcription of many
      inflammatory genes. The NF-kappaB subunit p50 is generally considered to be an
      inhibitory subunit of the NF-kappaB complex. We therefore hypothesize that NF
      kappaB p50 inhibits outward arterial remodeling. METHODS AND RESULTS: Carotid
      artery ligation in mice, induced outward remodeling in contralateral arteries of
      NF-kappaB p50(-/-) (p50(-/-)) and wild type (WT) arteries. p50(-/-) arteries
      showed more outward arterial remodeling than WT arteries (19894.0+/-3136.7
      microm(2) vs. 6120.7+/-2741.2 microm(2), respectively, P=0.006). In vitro,
      lipopolysaccharide induced higher cytokine expression levels in p50(-/-) cells
      compared to WT cells. In vivo, more outward remodeling in p50(-/-) arteries was
      associated with a decrease in collagen density and an increased influx of
      macrophages. CONCLUSIONS: The NF-kappaB p50 subunit is involved in outward
      arterial remodeling. This is probably due to modulation of macrophage influx and
      adventitial collagen, leading to enhanced flow-induced outward arterial
      remodeling after targeted deletion of NF-kappaB subunit p50.

PMID- 18617175
TI  - Periodontitis is associated with platelet activation.
AB  - There is an epidemiological association between periodontitis and cardiovascular
      disease (CVD). In periodontitis, low grade systemic inflammation and bacteremia
      occur regularly. Such events may contribute to platelet activation and subsequent
      pro-coagulant state. This study aimed to investigate platelet activation in
      periodontitis patients. The study is composed of two parts. In the first part,
      plasma levels of soluble(s) P-selectin and sCD40 ligand were measured as general
      markers of platelet activation in periodontitis patients (n=85) and in healthy
      controls (n=35). In the second part, surface-exposed P-selectin and the ligand
      binding conformation of the glycoprotein IIb-IIIa complex (binding of PAC-1
      antibody) were determined on individual platelets in whole blood of periodontitis
      patients (n=18) and controls (n=16). Patients had significantly elevated plasma
      levels of sP-selectin (P<0.001) and increased binding of PAC-1 on isolated
      platelets (P=0.033). Platelet activation was more pronounced in the patients with
      more severe periodontal disease, showing a severity-dependence. The levels of
      sCD40 ligand and of platelet-bound P-selectin were not increased. Periodontitis
      is associated with increased platelet activation. Since platelet activation
      contributes to a pro-coagulant state and constitutes a risk for atherothrombosis,
      platelet activation in periodontitis may partly explain the epidemiological
      association between periodontitis and CVD.

PMID- 18617176
TI  - Novel non-dimensional approach to comparison of wall shear stress distributions
      in coronary arteries of different groups of patients.
AB  - BACKGROUND: Local wall shear stress (WSS) has an impact on local remodelling of
      the vessel wall. WSS in turn strongly depends on local geometry. Our aim was to
      characterize patterns of local wall shear stress associated with distinct types
      of remodelling in coronary arteries. Vessel size and flow rates are different
      between patients, however. To compare distribution patterns of WSS in analogy to
      fluid-dynamic modelling, non-dimensional WSS/area functions are calculated.
      METHODS: Right coronary arteries from seven controls, five patients with coronary
      artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) were
      analyzed. Flow simulations were performed in three-dimensionally reconstructed
      coronary vessels from biplane angiographic projections. Local WSS was normalized
      as percentage of maximum value in a histogram (100 classes) and corresponding
      area was expressed as percentage of total area. RESULTS: The normalized WSS
      distribution was characterized by a single peak with a large lower tie in
      controls, a loss of the single peak and a stochastic distribution in AnCAD and a
      narrowing of the lower tie in CAD. Correct classification of 16/17 coronary
      arteries was feasible by Fisher's discriminant functions based on median WSS,
      mean diameter, percentage of area with WSS <or=0.4 Pa and with WSS >or=15 Pa.
      CONCLUSION: Normalized WSS distribution might be an efficient tool in comparing
      wall shear stress between different patient groups. Whether normalized WSS
      distribution curves are apt to grade severity of disease remains to be
      investigated.

PMID- 18617177
TI  - A three-pressure-sensor (3PS) system for monitoring ankle supination torque
      during sport motions.
AB  - This study presented a three-pressure-sensor (3PS) system for monitoring ankle
      supination torque during sport motions. Five male subjects wore a pair of cloth
      sport shoes and performed 10 trials of walking, running, cutting, vertical jump
      landing and stepping-down motions in a random sequence. A pair of pressure
      insoles (Novel Pedar model W, Germany) was inserted in the shoes for the
      measurement of plantar pressure at 100Hz. The ankle joint torque was calculated
      by a standard lower extremity inverse dynamic calculation procedure with the data
      obtained by a motion capture system (VICON, UK) and a force plate (AMTI, USA),
      and was presented in a supination/pronation plane with an oblique axis of
      rotation at the ankle joint. Stepwise linear regression analysis suggested that
      pressure data at three locations beneath the foot were essential for
      reconstructing the ankle supination torque. Another group of five male subjects
      participated in a validation test with the same procedure, but with the pressure
      insoles replaced by the 3PS system. Estimated ankle supination torque was
      calculated from the equation developed by the regression analysis. Results
      suggested that the correlation between the standard and estimated data was high
      (R=0.938). The overall root mean square error was 6.91Nm, which was about 6% of
      the peak values recorded in the five sport motions (113Nm). With the good
      estimation accuracy, tiny size and inexpensive cost, the 3PS system is readily
      available to be implanted in sport shoe for the estimation and monitoring of
      ankle supination torque during dynamic sport motions.

PMID- 18617178
TI  - Accuracy and precision of a method to study kinematics of the temporomandibular
      joint: combination of motion data and CT imaging.
AB  - The purpose of the study was to test the precision and accuracy of a method used
      to track selected landmarks during motion of the temporomandibular joint (TMJ). A
      precision phantom device was constructed and relative motions between two rigid
      bodies on the phantom device were measured using optoelectronic (OE) and
      electromagnetic (EM) motion tracking devices. The motion recordings were also
      combined with a 3D CT image for each type of motion tracking system (EM+CT and
      OE+CT) to mimic methods used in previous studies. In the OE and EM data
      collections, specific landmarks on the rigid bodies were determined using
      digitization. In the EM+CT and OE+CT data sets, the landmark locations were
      obtained from the CT images. 3D linear distances and 3D curvilinear path
      distances were calculated for the points. The accuracy and precision for all 4
      methods were evaluated (EM, OE, EM+CT and OE+CT). In addition, results were
      compared with and without the CT imaging (EM vs. EM+CT, OE vs. OE+CT). All
      systems overestimated the actual 3D curvilinear path lengths. All systems also
      underestimated the actual rotation values. The accuracy of all methods was within
      0.5mm for 3D curvilinear path calculations, 0.05mm for 3D linear distance
      calculations and 0.2 degrees for rotation calculations. In addition, Bland-Altman
      plots for each configuration of the systems suggest that measurements obtained
      from either system are repeatable and comparable.

PMID- 18617179
TI  - A mechanical supination sprain simulator for studying ankle supination sprain
      kinematics.
AB  - This study presents a free-fall mechanical supination sprain simulator for
      evaluating the ankle joint kinematics during a simulated ankle supination sprain
      injury. The device allows the foot to be in an anatomical position before the
      sudden motion, and also allows different degrees of supination, or a combination
      of inversion and plantarflexion. Five subjects performed simulated supination
      sprain trials in five different supination angles. Ankle motion was captured by a
      motion analysis system, and the ankle kinematics were reported in
      plantarflexion/dorsiflexion, inversion/eversion and internal/external rotation
      planes. Results showed that all sprain motions were not pure single-plane motions
      but were accompanied by motion in other two planes, therefore, different degrees
      of supination were achieved. The presented sprain simulator allows a more
      comprehensive study of the kinematics of ankle sprain when compared with some
      previous laboratory research designs.

PMID- 18617180
TI  - Importance of preswing rectus femoris activity in stiff-knee gait.
AB  - Stiff-knee gait is characterized by diminished and delayed knee flexion during
      swing. Rectus femoris transfer surgery, a common treatment for stiff-knee gait,
      is often recommended when a patient exhibits prolonged activity of the rectus
      femoris muscle during swing. Treatment outcomes are inconsistent, in part, due to
      limited understanding of the biomechanical factors contributing to stiff-knee
      gait. This study used a combination of gait analysis and dynamic simulation to
      examine how activity of the rectus femoris during swing, and prior to swing,
      contribute to knee flexion. A group of muscle-actuated dynamic simulations was
      created that accurately reproduced the gait dynamics of ten subjects with stiff
      knee gait. These simulations were used to examine the effects of rectus femoris
      activity on knee motion by eliminating rectus femoris activity during preswing
      and separately during early swing. The increase in peak knee flexion by
      eliminating rectus femoris activity during preswing (7.5+/-3.1 degrees ) was
      significantly greater on average (paired t-test, p=0.035) than during early swing
      (4.7+/-3.6 degrees ). These results suggest that preswing rectus femoris activity
      is at least as influential as early swing activity in limiting the knee flexion
      of persons with stiff-knee gait. In evaluating rectus femoris activity for
      treatment of stiff-knee gait, preswing as well as early swing activity should be
      examined.

PMID- 18617181
TI  - Application of silica-based hyper-crosslinked sulfonate-modified reversed
      stationary phases for separating highly hydrophilic basic compounds.
AB  - The separation and determination of hydrophilic basic compounds are of great
      importance in many fields including clinical and biological research,
      pharmaceutical development and forensic analysis. However, the most widely used
      analytical separation technique in these disciplines, reversed-phase liquid
      chromatography (RPLC), usually does not provide sufficient retention for several
      important classes of highly hydrophilic basic compounds including catecholamines,
      many drug metabolites and many drugs of abuse. Commonly eluents having little or
      no organic modifier and/or strong ion pairing agents must be used to achieve
      sufficient retention and separation. Use of highly aqueous eluents can lead to
      column failure by dewetting, resulting in poor retention, low selectivity and
      irreproducibility and slow recovery of performance. The use of a strong ion
      pairing agent to increase retention renders the separation incompatible with mass
      spectrometric detection and complicates preparative separations. This paper
      describes the successful applications of a novel type of silica-based, hyper
      crosslinked, sulfonate-modified reversed stationary phase, denoted as (-)SO(3)-HC
      C(8)-L, for the separation of highly hydrophilic cations and related compounds by
      a hydrophobically assisted cation-exchange mechanism. Compared to conventional
      reversed-phases, the (-)SO(3)-HC-C(8)-L phase showed significantly improved
      retention and separation selectivity for hydrophilic amines. Concurrently, due to
      the presence of both cation-exchange and reversed-phase retention mechanisms and
      the high acid stability of hyper-crosslinked phases, the separation can be
      optimized by changing the type or concentration of ionic additive or organic
      modifier, and by varying the column temperature. In addition, gradients generated
      by programming the concentration of either the ionic additive or the organic
      modifier can be applied to reduce the analysis time without compromising
      resolution. Furthermore, remarkably different chromatographic selectivities,
      especially toward cationic solutes, were observed upon comparing the (-)SO(3)-HC
      C(8)-L phase with conventional reversed-phases. We believe that the combination
      of these two types of stationary phases will be very useful in two-dimensional
      liquid chromatography.

PMID- 18617182
TI  - A molecular theory for particle nucleation: primary particle formation in
      emulsion polymerization.
AB  - Homogeneous nucleation is fundamentally important in emulsion polymerization. A
      molecular theory is proposed to quantify primary particle formation in the
      process. The proposed model divides a polymerization system into three portions:
      the domains formed by growing radicals, their surrounding aqueous solution, and
      dispersed monomer droplets. In general, the total free energy of the domains is
      contributed from the mixing among the molecules including monomer and water, the
      elasticity of oligomeric radical chains, and the transferable free energy of
      electrolytes; while that of the outer solution is from the mixing of monomer and
      water molecules and the transferable energy of electrolytes. Application of this
      theory to vinyl acetate emulsion polymerization has shown that the critical
      degree of polymerization (j(cri)) predicted is in a good agreement with the value
      derived from experimental data reported in literature. Furthermore, this model
      can also estimate the concentrations of VAc and water in the domain at the
      degrees of polymerization around j(cri).

PMID- 18617183
TI  - Multifocal granulomatous hepatitis caused by Actinobacillus pleuropneumoniae
      serotype 2 in slaughter pigs.
AB  - In a survey of 66 894 slaughter pigs, 11 animals from three farms were found to
      have multifocal granulomatous lesions in the liver, caused by Actinobacillus
      pleuropneumoniae serotype 2. The lesions consisted of epithelioid cells and
      multinucleated giant cells, with asteroid bodies and discernible gram-negative
      bacteria. Lymph nodes and spleen were occasionally affected. The results
      suggested that haematogenous spread had occurred from pre-existing pulmonary
      infections.

PMID- 18617184
TI  - Left main coronary thrombosis: unusual complication after radiofrequency ablation
      of left accessory atrioventricular pathway.
AB  - Radiofrequency ablation (RFA) has established itself as a first-line therapy for
      the curative treatment of many patients with supraventricular or atrioventricular
      tachycardias and has exhibited a generally low incidence of serious sequelae (N
      Engl J Med. 1991;324:1612; Lancet. 1991;337:1557). Coronary artery injury is a
      rare complication. We present a patient with an acute thrombotic total occlusion
      of the left main coronary artery immediately after the end of RFA who was
      successfully treated with emergency percutaneous transluminal coronary
      angioplasty. This case illustrates an unusual coronary complication of RFA and
      serves as an exceptional example of survival with a good short-term prognosis
      after this unusual etiology of myocardial infarction.

PMID- 18617185
TI  - Extracellular proteases and possible disease related virulence mechanisms of two
      marine bacteria implicated in an opportunistic bacterial infection of Nephrops
      norvegicus.
AB  - The extracellular products (ECP) secreted by two strains of gram-negative
      bacteria isolated from Nephrops norvegicus exhibiting signs of an opportunistic
      bacterial infection were investigated with the objective of understanding their
      role in the spoilage of host muscle tissue and identifying disease related
      virulence mechanisms. ECP from Vibrio sp. demonstrated no proteolytic activity.
      ECP from Pseudoalteromonas sp. (isolate N10) degraded several substrates,
      including azocasein and host muscle tissue. Proteolytic activity increased with
      temperature. Substrate-impregnated sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis of the effect of the isolates' ECP on the
      molecular weight of proteins derived from abdominal muscle tissue revealed that
      the ECP of Pseudoalteromonas sp. selectively degraded the myosin heavy chain,
      troponin-T, troponin-I, paramyosin and several unidentified muscle proteins
      approximately 110 kDa in size. Topomyosin was also reduced in quantity.
      Degradation of SDS-PAGE gels impregnated with host muscle proteins, by the ECP of
      Pseudoalteromonas sp. revealed 3 zones of proteolysis, with estimated molecular
      weights between 100 and 30 kDa, indicating multiple proteases in the ECP. Through
      the API ZYM system, both isolates demonstrated strong leucine arylamidase
      activity, with the Vibrio sp. showing strong acid phosphatase activity. These
      enzymes have been identified as disease related virulence mechanisms in other
      bacterial pathogens. There is likely a complex pathway to the final condition,
      involving virulence factors of other species and the stresses involved in capture
      and transport.

PMID- 18617186
TI  - Sex hormone receptor gene variation associated with phenotype in male
      hypertrophic cardiomyopathy patients.
AB  - Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous disease, which
      suggests that a number of factors exist which modify disease outcome. Gender may
      be one such factor as more males present with the disease compared with females.
      The aim of the present study was to determine if an association exists between
      genetic variation in sex hormone receptors and the development of left
      ventricular hypertrophy in HCM. The study population included 200 unrelated
      individuals from an Australian HCM cohort. Clinical evaluation was performed.
      Genetic analysis of the androgen receptor (AR), estrogen receptor 1 (ESR1),
      estrogen receptor 2 (ESR2), and aromatase (CYP19A1) genes, was carried out in all
      patients. Fewer (CAG)n repeats within the AR gene were significantly associated
      with higher maximal left ventricular wall thickness (LVWT) in males (P=0.008),
      adjusting for age. Male carriers of the A allele at SNP rs6915267, located in the
      promoter region of ESR1, had an 11% decrease in mean LVWT compared to male GG
      homozygotes (P=0.047). We report for the first time that variation at the AR gene
      is associated with left ventricular hypertrophy in males with HCM. Understanding
      the impact of sex hormones on phenotype will be helpful in the risk
      stratification and clinical management of HCM patients.

PMID- 18617187
TI  - Demonstration of a multistep mechanism for assembly of the SRP x SRP receptor
      complex: implications for the catalytic role of SRP RNA.
AB  - Two GTPases in the signal recognition particle (SRP) and its receptor (SR)
      control the delivery of newly synthesized proteins to the endoplasmic reticulum
      or plasma membrane. During the protein targeting reaction, the 4.5S SRP RNA
      accelerates the association between the two GTPases by 400-fold. Using
      fluorescence resonance energy transfer, we demonstrate here that formation of a
      stable SRP x SR complex involves two distinct steps: a fast initial association
      between SRP and SR to form a GTP-independent early complex and then a GTP
      dependent conformational rearrangement to form the stable final complex. We also
      found that the 4.5S SRP RNA significantly stabilizes the early GTP-independent
      intermediate. Furthermore, mutational analyses show that there is a strong
      correlation between the ability of the mutant SRP RNAs to stabilize the early
      intermediate and their ability to accelerate SRP x SR complex formation. We
      propose that the SRP RNA, by stabilizing the early intermediate, can give this
      transient intermediate a longer life time and therefore a higher probability to
      rearrange to the stable final complex. This provides a coherent model that
      explains how the 4.5S RNA exerts its catalytic role in SRP x SR complex assembly.

PMID- 18617189
TI  - Calorimetric and spectroscopic studies of Hoechst 33258: self-association and
      binding to non-cognate DNA.
AB  - Sequence and structure-specific molecular recognition of DNA by small molecules
      is an important goal in biophysical chemistry and drug discovery. Many candidate
      ligands possess flat aromatic surfaces and other molecular features that allow
      them to self-associate. In addition, non-specific binding to the target is a
      complicating feature of these interactions. Therefore, multiple equilibria are
      present and need to be accounted for in data analysis in order to obtain
      meaningful thermodynamic parameters. In order to address these issues we have
      systematically examined the bis-benzimidazole dye Hoechst 33258 (H33258) in terms
      of self-aggregation and binding to DNA oligonucleotides lacking any cognate minor
      groove A.T sites. This model system has been interrogated using isothermal
      titration calorimetry (ITC), circular dichroism (CD), fluorescence spectroscopy
      and pulsed gradient spin echo NMR. Three distinct binding events and ligand self
      aggregation have been identified and, where possible, quantified. H33258 self
      aggregation involves a step-wise aggregation mechanism, driven by stacking
      interactions. The DNA binding process includes two specific binding modes and non
      specific DNA-templated H33258 stacking. We have written novel ITC data-fitting
      software (IC-ITC; freely available to the biophysics community), which
      simultaneously fits ligand aggregation and ligand-DNA binding. Here, this
      numerical analysis, which uses simulated annealing of complex calorimetric data
      representing multiple coupled equilibria, is described.

PMID- 18617188
TI  - Cofilin increases the bending flexibility of actin filaments: implications for
      severing and cell mechanics.
AB  - We determined the flexural (bending) rigidities of actin and cofilactin filaments
      from a cosine correlation function analysis of their thermally driven, two
      dimensional fluctuations in shape. The persistence length of actin filaments is
      9.8 microm, corresponding to a flexural rigidity of 0.040 pN microm(2). Cofilin
      binding lowers the persistence length approximately 5-fold to a value of 2.2
      microm and the filament flexural rigidity to 0.0091 pN microm(2). That cofilin
      decorated filaments are more flexible than native filaments despite an increased
      mass indicates that cofilin binding weakens and redistributes stabilizing subunit
      interactions of filaments. We favor a mechanism in which the increased
      flexibility of cofilin-decorated filaments results from the linked dissociation
      of filament-stabilizing ions and reorganization of actin subdomain 2 and as a
      consequence promotes severing due to a mechanical asymmetry. Knowledge of the
      effects of cofilin on actin filament bending mechanics, together with our
      previous analysis of torsional stiffness, provide a quantitative measure of the
      mechanical changes in actin filaments associated with cofilin binding, and
      suggest that the overall mechanical and force-producing properties of cells can
      be modulated by cofilin activity.

PMID- 18617190
TI  - Secular trends in poisonings leading to hospital admission among Finnish children
      and adolescents between 1971 and 2005.
AB  - OBJECTIVE: To investigate the secular trends in childhood poisonings leading to
      hospitalization in Finland. STUDY DESIGN: All children and adolescents age 0 to
      19 years hospitalized in Finland with the primary diagnosis of poisoning between
      1971 and 2005 were identified using the International Classification of Diseases.
      RESULTS: During the study period, there were 41 862 hospitalizations with 96 427
      hospital bed days for poisoning in 38 582 children and adolescents. The incidence
      of hospitalization declined from 91.3 admissions per 100 000 person-years in boys
      and 105.2 per person-years in girls in 1971 to 64.8 in boys and 83.5 in girls in
      2005. In the 0- to 4-year age group, admissions declined by 51%. Hospitalizations
      for alcohol poisoning increased 1.7-fold (95% confidence interval = 1.4 to 2.2)
      in boys and 2.4-fold (95% confidence interval = 1.8 to 3.3) in girls. Alcohol
      poisoning was the primary diagnosis in 53% of those in the 10- to 14-year age
      group. CONCLUSIONS: Poisoning remains an important cause of morbidity in Finnish
      children and adolescents despite the decreased overall incidence of poisonings
      leading to hospitalization between 1971 and 2005. The increasing trend of
      hospital admissions for alcohol poisoning, especially in 10- to 14-year-olds, is
      noteworthy. Effective primary prevention programs and adult supervision should be
      targeted at reducing alcohol consumption and alcohol-related poisonings in youth.

PMID- 18617191
TI  - Quality of care of children in the emergency department: association with
      hospital setting and physician training.
AB  - OBJECTIVE: To investigate differences in the quality of emergency care for
      children related to differences in hospital setting, physician training, and
      demographic factors. STUDY DESIGN: This was a retrospective cohort study of a
      consecutive sample of children presenting with high-acuity illnesses or injuries
      at 4 rural non-children's hospitals (RNCHs) and 1 academic urban children's
      hospital (UCH). Two of 4 study physicians independently rated quality of care
      using a validated implicit review instrument. Hierarchical modeling was used to
      estimate quality of care (scored from 5 to 35) across hospital settings and by
      physician training. RESULTS: A total of 304 patients presenting to the RNCHs and
      the UCH were studied. Quality was lower (difference = -3.23; 95% confidence
      interval [CI] = -4.48 to -1.98) at the RNCHs compared with the UCH. Pediatric
      emergency medicine (PEM) physicians provided better care than family medicine
      (FM) physicians and those in the "other" category (difference = -3.34, 95% CI = 
      5.40 to -1.27 and -3.12, 95% CI = -5.25 to -0.99, respectively). Quality of care
      did not differ significantly between PEM and general emergency medicine (GEM)
      physicians in general, or between GEM and PEM physicians at the UCH; however, GEM
      physicians at the RNCHs provided care of lesser quality than PEM physicians at
      the UCH (difference = -2.75; 95% CI = -5.40 to -0.05). Older children received
      better care. CONCLUSIONS: The quality of care provided to children is associated
      with age, hospital setting, and physician training.

PMID- 18617192
TI  - Hyperphosphorylation of tau protein in superficial CNS siderosis.
AB  - In superficial CNS siderosis chronic subarachnoidal hemorrhage leads to
      hemosiderin deposits in the subpial layers of the brain and spinal cord. Many
      years usually pass between the initial event causing chronic bleedings and the
      development of cerebellar ataxia, sensory hearing loss and various sensorimotor
      deficits. The only therapeutic option is to identify and eliminate the bleeding
      source. Otherwise slow relentless decline to a bedridden state and dementia is
      usually unavoidable. However, it is not known how precisely leptomeningeal
      hemosiderin deposits induce progressive neurodegeneration. Here we present the
      first report of a patient with superficial CNS siderosis in whom cerebrospinal
      fluid biomarkers of brain damage were assessed. Levels of neurofilament light
      protein, glial fibrillary acidic protein, total tau protein and, most
      importantly, hyperphosphorylated tau protein were increased. The results indicate
      that in superficial CNS siderosis neurodegeneration may be secondary to iron
      toxicity and oxidative stress. Similar mechanisms have been suggested for other
      neurodegenerative disorders such as Alzheimer's disease.

PMID- 18617193
TI  - Homocysteine, folate and vitamin B(12) in puerperal cerebral venous thrombosis.
AB  - BACKGROUND AND OBJECTIVE: Hyperhomocysteinemia (hyper-Hcy) is a known risk factor
      for venous thrombosis, but few studies document the risk in puerperal cerebral
      venous thrombosis (CVT). Nutritional folate and vitamin B(12) deficiency can
      cause hyper-Hcy and pregnancy may contribute to this deficiency. We studied the
      association of plasma total homocysteine (tHcy), folate and vitamin B(12) levels
      with puerperal CVT through a case-control study. METHODS: Sixty women with
      puerperal CVT and 64 healthy puerperal controls were recruited. Plasma fasting
      tHcy was estimated by high pressure liquid chromatography using coulometric
      electrochemical detection. Vitamin B(12) and folate were measured by
      radioimmunoassay. Risk of puerperal CVT was estimated for each of the three
      variables. RESULTS: Adjusted odds ratio for the risk of puerperal CVT with hyper
      Hcy (>90th percentile) was 10.8 (95% CI: 4.0-29.4; adjusted for vitamin B(12) and
      folate levels). Low folate and vitamin B(12) levels (<10th percentile) did not
      increase the risk for puerperal CVT. There was a significant inverse correlation
      between folate and tHcy levels (rho=-0.471, p<0.001). CONCLUSIONS:
      Hyperhomocysteinemia is associated with an increased risk of puerperal CVT
      occurring in Indian women and low folate levels contribute significantly to hyper
      Hcy. Regular antenatal folate and vitamin B(12) supplementation is likely to
      lower puerperal tHcy levels, but its clinical benefit needs to be tested by large
      therapeutic trials.

PMID- 18617194
TI  - Ethanol inhibition of kainate receptor-mediated excitatory neurotransmission in
      the rat basolateral nucleus of the amygdala.
AB  - The neurobiological mechanisms governing alcohol-induced alterations in anxiety
      like behaviors are not fully understood. Given that the amygdala is a major
      emotional center in the brain and regulates the expression of both learned fear
      and anxiety, neurotransmitter systems within the basolateral amygdala represent
      likely mechanisms governing the anxiety-related effects of acute ethanol
      exposure. It is well established that, within the glutamatergic system, N-methyl
      d-aspartate (NMDA)-type receptors are particularly sensitive to intoxicating
      concentrations of ethanol. However, recent evidence suggests that kainate-type
      glutamate receptors are sensitive to ethanol as well. Therefore, we examined the
      effect of acute ethanol on kainate receptor (KA-R)-mediated synaptic transmission
      in the basolateral amygdala (BLA) of Sprague-Dawley rats. Acute ethanol decreased
      KA-R-mediated excitatory postsynaptic currents (EPSCs) in the BLA in a
      concentration-dependent manner. Ethanol also inhibited currents evoked by focal
      application of the kainate receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-tert
      butylisoxazol-4-yl) propanoic acid (ATPA), and ethanol inhibition of kainate
      EPSCs was not associated with a change in paired-pulse ratio, suggesting a
      postsynaptic mechanism of ethanol action. The neurophysiological consequences of
      this acute sensitivity were tested by measuring ethanol's effects on KA-R
      dependent modulation of synaptic plasticity. Acute ethanol, like the GluR5
      specific antagonist (R,S)-3-(2-carboxybenzyl)willardiine (UBP 296), robustly
      diminished ATPA-induced increases in synaptic efficacy. Lastly, to better
      understand the relationship between KA-R activity and anxiety-like behavior, we
      bilaterally microinjected ATPA directly into the BLA. We observed an increase in
      measures of anxiety-like behavior, assessed in the light/dark box, with no change
      in locomotor activity. This evidence suggests that kainate receptors in the BLA
      are inhibited by pharmacologically relevant concentrations of ethanol and may
      contribute to some of the acute anxiolytic effects of this drug.

PMID- 18617195
TI  - Imaging dopamine's role in drug abuse and addiction.
AB  - Dopamine is involved in drug reinforcement but its role in addiction is less
      clear. Here we describe PET imaging studies that investigate dopamine's
      involvement in drug abuse in the human brain. In humans the reinforcing effects
      of drugs are associated with large and fast increases in extracellular dopamine,
      which mimic those induced by physiological dopamine cell firing but are more
      intense and protracted. Since dopamine cells fire in response to salient stimuli,
      supraphysiological activation by drugs is experienced as highly salient (driving
      attention, arousal, conditioned learning and motivation) and with repeated drug
      use may raise the thresholds required for dopamine cell activation and signaling.
      Indeed, imaging studies show that drug abusers have marked decreases in dopamine
      D2 receptors and in dopamine release. This decrease in dopamine function is
      associated with reduced regional activity in orbitofrontal cortex (involved in
      salience attribution; its disruption results in compulsive behaviors), cingulate
      gyrus (involved in inhibitory control; its disruption results in impulsivity) and
      dorsolateral prefrontal cortex (involved in executive function; its disruption
      results in impaired regulation of intentional actions). In parallel, conditioning
      triggered by drugs leads to enhanced dopamine signaling when exposed to
      conditioned cues, which then drives the motivation to procure the drug in part by
      activation of prefrontal and striatal regions. These findings implicate deficits
      in dopamine activity-inked with prefrontal and striatal deregulation-in the loss
      of control and compulsive drug intake that results when the addicted person takes
      the drugs or is exposed to conditioned cues. The decreased dopamine function in
      addicted individuals also reduces their sensitivity to natural reinforcers.
      Therapeutic interventions aimed at restoring brain dopaminergic tone and activity
      of cortical projection regions could improve prefrontal function, enhance
      inhibitory control and interfere with impulsivity and compulsive drug
      administration while helping to motivate the addicted person to engage in non
      drug related behaviors.

PMID- 18617196
TI  - Repeated risperidone administration during puberty prevents the generation of the
      aggressive phenotype in a developmentally immature animal model of escalated
      aggression.
AB  - Risperidone has been shown to be clinically effective for the treatment of
      aggressive behavior in children, yet until recently no information was available
      regarding whether risperidone exhibits aggression-specific suppression in
      preclinical studies employing validated developmentally immature animal models of
      escalated aggression. Recently, using a pharmacologic animal model of escalated
      offensive aggression, we reported that acute risperidone treatment selectively
      and dose-dependently reduces the expression of the adult aggressive phenotype,
      with a significant reduction in aggressive responses observed at 0.1 mg/kg, i.e.,
      a dose within the range administered to children and adolescents in the clinical
      setting. This study examined whether repeated exposure to risperidone during
      puberty would prevent the generation of the highly escalated aggressive phenotype
      in this animal model. To test this hypothesis, the aggression-eliciting stimulus
      (i.e., cocaine hydrochloride, 0.5 mg/kg/dayx28 days) was co-administered with an
      aggression-suppressing dose of risperidone (i.e., 0.1 mg/kg/day) during different
      time frames of puberty and for varied lengths of time (i.e., 1-4 weeks), and then
      animals were scored for targeted measures of offensive aggression during late
      puberty. Risperidone administration prevented the generation of the adult
      aggressive phenotype, with a complete blockade of matured offensive responses
      (i.e., lateral attacks and flank/rump bites) seen only after prolonged periods of
      exposure to risperidone (i.e., 3-4 weeks). The selective prevention of these
      aggressive responses, while leaving other measures of aggression intact (e.g.,
      upright offensive postures), suggest that risperidone is acting in a highly
      discriminatory anti-aggressive fashion, targeting neurobehavioral elements
      important for the mature aggressive response pattern.

PMID- 18617197
TI  - Light filtering by epidermal flavonoids during the resistant response of cotton
      to Xanthomonas protects leaf tissue from light-dependent phytoalexin toxicity.
AB  - 2,7-Dihydroxycadalene and lacinilene C, sesquiterpenoid phytoalexins that
      accumulate at infection sites during the hypersensitive resistant response of
      cotton foliage to Xanthomonas campestris pv. malvacearum, have light-dependent
      toxicity toward host cells, as well as toward the bacterial pathogen. Adaxial
      epidermal cells surrounding and sometimes covering infection sites turn red. The
      red cells exhibited 3-4-fold higher absorption at the photoactivating wavelengths
      of sunlight than nearby colorless epidermal cells. Red epidermal cells protected
      underlying palisade mesophyll cells from the toxic effects of 2,7
      dihydroxycadalene plus sunlight, indicating a role for epidermal pigments in
      protecting living cells that surround infection sites from toxic effects of the
      plant's own phytoalexins. A semi-quantitative survey of UV-absorbing substances
      extracted from epidermal strips from inoculated and mock-inoculated cotyledons
      indicated that the principal increase in capacity to absorb the photoactivating
      wavelengths was due to a red anthocyanin and a yellow flavonol, which were
      identified as cyanidin-3-O-beta-glucoside and quercetin-3-O-beta-glucoside,
      respectively.

PMID- 18617198
TI  - Ascorbic acid potentiates the cytotoxicity of the naphthoquinone 5-methoxy-3,4
      dehydroxanthomegnin.
AB  - The interaction of ascorbic acid with 5-methoxy-3,4-dehydroxanthomegnin, an 1,4
      naphthoquinone, was investigated using the cytotoxic index for McCoy cells by
      neutral red assay. The synergistic effect was observed when such compounds were
      added simultaneously, most probably due to hydrogen peroxide being generated by
      ascorbate-driven 5-methoxy-3,4-dehydroxanthomegnin redox cycling. Incubation of
      cells in the presence of 5-methoxy-3,4-dehydroxanthomegnin/ascorbic
      acid/catalase, an enzyme that destroys H2O2, resulted in an increase of cell
      survival, reinforcing the involvement of hydrogen peroxide generated as an
      important oxidizing agent that kills McCoy cells.

PMID- 18617199
TI  - Looking for the unusual suspects: a Salmonella Dublin outbreak investigation.

PMID- 18617200
TI  - Health impacts of supportive housing for homeless youth: a pilot study.

PMID- 18617201
TI  - Effect of physician strategies for coping with the US medical malpractise crisis
      on healthcare delivery and patient access to healthcare.
AB  - The medical liability system in the USA is once again mired in a major
      malpractise crisis. Physicians have struggled to acquire liability coverage
      during the crisis, because malpractise insurance has been unaffordable and
      unavailable. This limited access to affordable liability coverage has prompted
      some physicians to utilize strategies that reduce their malpractise risk. These
      strategies have included eliminating high-risk services, defensive medicine, and
      establishing medical practises in states with affordable malpractise insurance.
      The fear of malpractise liability and possible financial ruin may justify the use
      of these strategies. However, these tactics could create a serious public health
      problem, because they are having a negative impact on healthcare delivery and
      patient access to healthcare.

PMID- 18617202
TI  - Taiwan's national health insurance system and the application of preventive care:
      the case of Pap smear testing.

PMID- 18617203
TI  - Biochemical and hematological reference ranges for Amazon freshwater turtle,
      Podocnemis expansa (Reptilia: Pelomedusidae), with morphologic assessment of
      blood cells.
AB  - Blood parameters are useful to measure physiological disturbances in chelonians.
      Thus they can provide important information for the diagnosis and prognosis of
      diseases. The aim of this paper was to determine the reference range of plasma
      glucose, total protein, triglycerides, cholesterol and urea levels, as well as
      hematocrit, hemoglobin, red blood cell, thrombocyte and white blood cell counts
      for healthy Podocnemis expansa (Schweigger, 1812), bred in a turtle farm in the
      Amazonas State, Brazil. Plasma glucose, hemoglobin, mean corpuscular volume
      (MCV), lymphocytes and heterophils were the parameters with the smallest
      variations. Significant (p<0.001) correlations between red blood cells count and
      hematocrit and hemoglobin concentration were found. Turtle P. expansa had
      lymphocytes, azurophils, heterophils, eosinophils and basophils with morphologic
      features similar to the ones of others turtles species. No investigated blood
      parameter was influenced by sex. In further studies, the established reference
      ranges might be useful for the health assessment of this turtle species.

PMID- 18617204
TI  - [Osteosynthesis of the temporal articular tubercle].

PMID- 18617205
TI  - [Bad news!].

PMID- 18617206
TI  - kDNA gene signatures of Trypanosoma cruzi in blood and oesophageal mucosa from
      chronic chagasic patients.
AB  - Trypanosoma cruzi presents a high degree of intraspecific variability, with
      possible implications for the pathogenesis of Chagas disease. The aim of this
      study was to evaluate T. cruzi kDNA minicircle gene signatures using the low
      stringency single-specific-primer PCR technique in both peripheral blood and
      oesophageal mucosa from chronic chagasic patients, with or without megaesophagus,
      alone or in combination with cardiopathy and megacolon. It was not possible to
      identify a uniform pattern of shared bands between blood and oesophageal mucosa
      samples from individuals with the same clinical form or mixed forms, suggesting
      multiple T. cruzi infections with differential tissue tropism. Thus, the results
      indicate that there is an intense intraspecific variability in the hypervariable
      regions of T. cruzi kDNA, which has so far made it impossible to correlate the
      genetic profile of this structure with the clinical manifestations of Chagas
      disease.

PMID- 18617207
TI  - Healthcare seeking behaviour for Buruli ulcer in Benin: a model to capture
      therapy choice of patients and healthy community members.
AB  - Buruli ulcer is a devastating condition emerging in West Africa. We investigated
      why patients often report late to the hospital. Health seeking behaviour
      determinants and stigma were studied by in-depth interviews in patients treated
      in hospital (n=107), patients treated traditionally (n=46) of whom 22 had active
      disease, and healthy community control subjects (n=107). We developed a model
      capturing internal and external factors affecting decision making. With
      increasing severity, extent and duration of Buruli ulcer, a shift of influencing
      factors on health seeking behaviour appears to occur. Factors causing delay in
      presenting to hospital were the use of traditional medicine before presenting at
      the treatment centre; costs and duration of admission; disease considered not
      serious enough; witchcraft perceived as the cause of disease; and fear of
      treatment, which patients expected to be amputation. This study confirms the
      importance of self-treatment and traditional healing in this area. Our study was
      performed before antimicrobial treatment was introduced in Benin; we suggest that
      this model and the results from this analysis should be used as a baseline from
      which to measure the influence of the introduction of antimicrobial treatment on
      health seeking behaviour for Buruli ulcer in Benin.

PMID- 18617208
TI  - A case series of dengue fever with altered consciousness and electroencephalogram
      changes in Sri Lanka.
AB  - We describe six serology-positive dengue patients presenting sporadically over 8
      years, who lapsed into coma and showed generalized irregular slow waves in
      consecutive electroencephalograms (EEG) in the absence of any structural brain
      damage. The mean age was 41 years (range 16-65). All had fever, headache and
      vomiting for 3 days (range 2-4) on admission and developed coma after 24 h. Five
      patients developed generalized convulsions and two showed generalized paroxysmal
      spike-wave discharges in the EEG. All regained normal consciousness within 36 h.
      In two patients, slow waves in the EEG persisted for 6 and 18 months.

PMID- 18617209
TI  - Anaemia and iron deficiency anaemia among aboriginal schoolchildren in rural
      Peninsular Malaysia: an update on a continuing problem.
AB  - A cross-sectional study to determine the current prevalence of anaemia and iron
      deficiency anaemia (IDA) and to investigate the possible risk factors for IDA was
      carried out on 241 aboriginal schoolchildren (120 boys, 121 girls) aged 7-12
      years and living in remote areas in Pos Betau, Pahang, Malaysia. Haemoglobin (Hb)
      level was measured and serum iron status was assessed by serum ferritin (SF),
      serum iron (SI) and total iron binding capacity measurements. Socioeconomic data
      were collected using pre-tested questionnaires. All children were screened for
      intestinal parasitic infections. Overall, 48.5% (95% CI 42.3-54.8) of children
      were anaemic (Hb<12 g/dl). The prevalence of IDA was 34% (95% CI 28.3-40.2),
      which accounted for 70.1% of the anaemia cases. The prevalence of IDA was
      significantly higher in females than males. Low levels of mothers' education and
      low household income were identified as risk factors for IDA. Severe trichuriasis
      also found to be associated with low SF and SI. Logistic regression confirmed low
      levels of mothers' education and gender as significant risk factors for IDA.
      Improvement of socioeconomic status and health education together with periodic
      mass deworming should be included in public health strategies for the control and
      prevention of anaemia and IDA in this population.

PMID- 18617210
TI  - Coordinated induction of Nrf2 target genes protects against iron
      nitrilotriacetate (FeNTA)-induced nephrotoxicity.
AB  - The iron chelate, ferric nitrilotriacetate (FeNTA), induces acute proximal
      tubular necrosis as a consequence of lipid peroxidation and oxidative tissue
      damage. Chronic exposure of FeNTA leads to a high incidence of renal
      adenocarcinomas in rodents. NF-E2-related factor 2 (Nrf2) is a transcription
      factor that is activated by oxidative stress and electrophiles, and regulates the
      basal and inducible expression of numerous detoxifying and antioxidant genes. To
      determine the roles of Nrf2 in regulating renal gene expression and protecting
      against oxidative stress-induced kidney damage, wild-type and Nrf2-null mice were
      administered FeNTA. Renal Nrf2 protein translocated to the nucleus at 6h after
      FeNTA treatment. FeNTA increased mRNA levels of Nrf2 target genes, including
      NQO1, GCLC, GSTpi1/2, Mrp1, 2, and 4 in kidneys from wild-type mice, but not Nrf2
      null mice. Protein expression of NQO1, a prototypical Nrf2 target gene, was
      increased in wild-type mice, with no change in Nrf2-null mice. FeNTA produced
      more nephrotoxicity in Nrf2-null mice than wild-type mice as indicated by higher
      serum urea nitrogen and creatinine levels, as more urinary NAG, stronger 4
      hydroxynonenal protein adduct staining, and more extensive proximal tubule
      damage. Furthermore, pretreatment with CDDO-Im, a potent small molecule Nrf2
      activator, protected mice against FeNTA-induced renal toxicity. Collectively,
      these results suggest that activation of Nrf2 protects mouse kidneys from FeNTA
      induced oxidative stress damage by coordinately up-regulating the expression of
      cytoprotective genes.

PMID- 18617211
TI  - Stringhalt in Brazilian horses caused by Hypochaeris radicata.
AB  - Two outbreaks of Hypochaeris radicata-induced Australian stringhalt involving two
      farms and seven horses from southern Brazil are reported here. Subsequently, the
      disease was experimentally reproduced in a feeding trial with one colt fed H.
      radicata from the suspect paddocks. Fresh H. radicata was fed to the experimental
      animal for 50 days at an average daily dosage of 9.8 kg. Initially, the plant was
      collected from the paddock where the clinical disease occurred and was fed for 19
      consecutive days producing mild clinical signs. However, on days 20-23 fresh
      plant was collected from a neighboring farm where the disease had not been
      reported and fed to the colt at which time the colt appeared to recover.
      Therefore, plant collections from the original suspect paddock resumed and
      feeding trials continued with clinical signs reoccurring by day 36, and
      increasing in intensity from days 43-50 after which plant administration was
      stopped. Within 15 days after ending the feeding trial with H. radicata, the colt
      appeared to have recovered. This experimental reproduction of stringhalt in a
      single colt fed H. radicata demonstrated that the two outbreaks of the disease
      resulted from this plant. Interestingly, the change in location for collection of
      plant material 19 days into the treatment, and the subsequent recovery of the
      colt, would suggest that plant material may differ in toxicity depending on
      location.

PMID- 18617212
TI  - Neutralization of lethality and proteolytic activities of Malayan pit viper
      (Calloselasma rhodostoma) venom with North American Virginia opossum (Didelphis
      virginiana) serum.
AB  - Malayan pit viper (Calloselasma rhodostoma) envenomation is a major health
      problem in South East Asia. During envenomation, venom components mainly affect
      the hemostatic system. The sera from the North American Virginia opossums
      (Didelphis virginiana) were able to neutralize the venom of the Malayan pit
      viper. These natural inhibitors could be explored as potential therapeutics
      against envenomations of a variety of venomous snake species in different
      geographical habitats.

PMID- 18617213
TI  - A low molecular weight serine protease: Purification and characterization from
      Hippasa agelenoides (funnel web) spider venom gland extract.
AB  - Despite the long history [Kaiser, E., 1956. Enzymatic activity of spider venoms.
      In: Buckley, E.E., Porges, N. (Eds.), Venoms. American Association for the
      Advancement of Science, Washington, DC, pp. 91-93] on proteolytic activity, no
      study so far claims the isolation of a serine protease from the spider
      venom/venom gland extract. Therefore, the present study describes the isolation
      and characterization of a low molecular weight serine protease from Hippasa
      agelenoides venom gland extract. The protease (Hag-protease) was purified to
      homogeneity using the combination of gel-permeation and ion-exchange
      chromatography. The molecular mass was found to be 16.350 kDa by matrix-assisted
      laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Hag
      protease was optimally active at pH 7.5 and temperature of 37 degrees C. PMSF
      abolished the enzyme activity while EDTA, EGTA, IAA, 1, 10-phenanthrolene did
      not. It hydrolyzed proteins such as casein, fibronectin and collagen type-I dose
      dependently but did not degrade gelatin and collagen type-IV. The isolated
      protease was non-lethal and devoid of hemorrhagic, myotoxic and edema forming
      activities. The light microscopy of Hag-protease treated skin tissue sections at
      the site of injection showed extensive damage of extracellular matrix (ECM) of
      hypodermis without causing any damage to blood vessels and capillaries. Similar
      damage of ECM of muscle tissue sections without affecting myocytes was noticed.
      Hag-protease was found to be procoagulant in property when studied plasma
      recalcification time.

PMID- 18617214
TI  - A non-radioactive ligand-binding assay for detection of cyanobacterial anatoxins
      using Torpedo electrocyte membranes.
AB  - Anatoxin-a (ANTX) and homoanatoxin-a (HANTX), neurotoxins exclusively produced by
      cyanobacteria (LD(50) 200-250 microg kg(-1), i.p. mouse), are agonists of the
      nicotinic acetylcholine receptors (nAChRs) to which they tightly bind. We have
      exploited the high affinity of these neurotoxins for the nicotinic receptors to
      develop a non-radioactive ligand-binding assay using Torpedo electrocyte
      membranes and biotinylated alpha-bungarotoxin (Biotin-BgTx) as tracer for
      detection of this class of toxins. The affinity of the Torpedo nAChRs for Biotin
      BgTx was determined by chemiluminescence (K(d)=1.2 x 10(-8)M Biotin-BgTx) or
      color development (K(d)=3.5 x 10(-8)M Biotin-BgTx). Binding of ANTX or HANTX to
      the nAChRs competitively inhibits the binding of Biotin-BgTx to the receptors in
      a concentration-dependent manner (chemiluminescence: IC(50): 6.2 x 10(-8)M ANTX;
      color development: IC(50): 1.7 x 10(-8)M ANTX). The proposed method was validated
      by HPLC/MS with detection in the single ion recording mode. The non-radioactive
      ligand receptor-binding assay was successfully applied to the analysis of
      extracts prepared from cyanobacteria in culture and from natural habitats, as
      well as from aqueous samples. This method is suitable for ANTX and HANTX early
      survey of environmental samples since it requires minimal manipulations, is
      highly sensitive and gives consistent signal-to-noise ratios.

PMID- 18617215
TI  - Porcine circovirus type 2 displays pluripotency in cell targeting.
AB  - Porcine circovirus type 2 (PCV2) is the causative agent of a multifactorial
      disease associated with immunocompromisation and co-infections. In vivo, viral
      DNA and antigens are found in monocytic, epithelial and endothelial cells. Of
      these, PCV2 replication has only been studied in monocytic cells, in which little
      or no replication was identified. Accordingly, PCV2 infection was studied in the
      endothelial cell line PEDSV.15, aortic endothelial cells, gut epithelial cells,
      fibrocytes and dendritic cells (DC). In all cells except DC PCV2 replication was
      detectable, with an increase in the levels of capsid and replicase protein.
      Variations in endocytic activity, virus binding and uptake did not relate to the
      replication efficiency in a particular cell. Furthermore, replication did not
      correlate to cell proliferation, although a close association of viral proteins
      with chromatin in dividing cells was observed. No alteration in the division rate
      of PCV2-infected cultures was measurable, relating to replicase expression in
      only a small minority of the cells. In conclusion, the broad cell targeting of
      PCV2 offers an explanation for its widespread tissue distribution.

PMID- 18617216
TI  - Illusory motion reversals from unambiguous motion with visual, proprioceptive,
      and tactile stimuli.
AB  - While viewing an unambiguously rotating circular array of bars for an extended
      period, most perceive the array to occasionally move in the direction opposite to
      its true motion. We find that this alternation in perception has similar dynamics
      to rivalry, including little correlation among the durations of successive
      percepts. We also describe analogous reversals in touch and in proprioception. In
      the proprioceptive case, biceps vibration induces illusory forearm extension.
      Occasionally, although the same stimulation continues, reversals occur-flexion is
      perceived rather than extension. Temporal sampling is often invoked to explain
      the visual reversals but it cannot explain these proprioceptive reversals.
      Instead, after initial adaptation to the stimulus, rivalry between signals
      indicating the opposing directions could potentially explain reversals in all
      three modalities.

PMID- 18617217
TI  - PCDDs/PCDFs, dl-PCBs and HCB in the flue gas from coal fired CFB boilers.
AB  - The aim of the project was to measure the actual emissions of polychlorinated
      dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like
      polychlorinated biphenyls (dl-PCBs) and hexachlorobenzene (HCB) from four
      selected power plants in Poland in order to update the national inventory of
      PCDDs/PCDFs emission. Relatively low PCDDs/PCDFs as well as dl-PCBs
      concentrations in flue gas obtained in measurements in this study for four
      different circulated fluidized bed (CFB) boilers indicate practical absence of
      any hazards caused by PCDDs/PCDFs emission from these units. The results of
      PCDDs/PCDFs determination obtained in this study indicate that hard coal
      combustion in large CFB in the four central heating plants (CHP) is not a
      significant source of PCDDs/PCDFs emission to the environment even if operated by
      co-firing of waste coal. PCDDs/PCDFs concentration in flue gases as well as
      emission factors were recorded in the range of 0.012-0.060 ng I-TEQ/m(n)(3) and
      7.51-46.4 microg I-TEQ/TJ, respectively. Dl-PCBs concentration was practically
      below the LOQ=0.006 ng WHO-PCB TEQ/m(n)(3) in all experiments. HCB concentration
      as well as emission factors were recorded in the range of 11.5-42.0 ng/m(n)(3)
      and 6.19-26.7 mg/TJ, respectively, where the highest value was obtained for co
      firing of waste coal, however. Obtained in this work emission factors will be
      used for national emission inventory purposes instead of the factors proposed by
      Toolkit or taken from previous measurements. However, consideration should be
      given to the fact that the measurements in most cases are related to single
      installations. Therefore, the need for further development of national factors
      for the power generation industry in Poland is desired.

PMID- 18617218
TI  - Aqueous photolysis of tetracycline and toxicity of photolytic products to
      luminescent bacteria.
AB  - The extensive utilization of antibiotics in the pharmaceutical therapies and
      agricultural husbandry has led to the worldwide pollution in environments. In
      this study the photolysis behaviors of tetracycline (TC) and toxicity of its
      degradation products were investigated. The results showed that TC photolysis
      followed first-order kinetics. The photolysis rate was found to be dependent on
      the initial TC concentration and increasing TC concentration from 10 to 40mgl(-1)
      led to the decrease of the photolysis rate constant from 0.0045min(-1) to
      0.0014min(-1). TC photolysis was highly pH-dependent and strongly enhanced at
      high pH value. Markedly elevated TC photolysis was also observed in the presence
      of nitrate and dissolved organic matter. Upon irradiation for 300min, only 15%
      reduction of total organic carbon (TOC) occurred in spite of quick conversion of
      73% of TC, suggesting that a majority of TC transformed into intermediate
      products without complete mineralization. The intermediate products from TC
      photolysis were analyzed using high-performance liquid chromatography
      electrospray ionisation-mass spectrometry (HPLC-ESI-MS) and the main photolysis
      products of TC were proposed. The toxicity of the photolysis compounds was
      evaluated using luminescent bacterium, and the results revealed that the toxicity
      increased with irradiation, indicative of a higher adversity risk of the
      degradation products of TC on bacteria upon photolysis.

PMID- 18617219
TI  - Paleoanthropology of the Kibish Formation, southern Ethiopia: Introduction.
AB  - Cranial and skeletal remains of modern humans, Homo sapiens, were discovered in
      the Kibish Formation in 1967 by a team from the Kenya National Museums directed
      by Richard Leakey. Omo I, from Kamoya's Hominid Site (KHS), consists of much of a
      skeleton, including most of the cranial vault, parts of the face and mandible,
      and many postcranial elements. Omo II, from Paul's Hominid Site (PHS), is a
      virtually complete calvaria. Only a limited fauna and a few stone artifacts
      attributed to the Middle Stone Age were recovered in conjunction with the fossil
      hominids. The available dating techniques suggested a very early age, over 100
      ka, for Member I, from which the Omo I and Omo II fossils were recovered.
      However, in subsequent decades, the reliability of the dates and the provenance
      of the Kibish hominids were repeatedly questioned. The papers in this volume
      provide a detailed stratigraphic analysis of the Kibish Formation and a series of
      new radiometric dates that indicate an age of 196+/-2 ka for Member I and 104+/-1
      for Member III, confirming the antiquity of the lower parts of the Kibish
      Formation and, in turn, the fossils from Member I. Studies of the postcranial
      remains of Omo I indicate an overall modern human morphology with a number of
      primitive features. Studies of an extensive lithic record from Members I and III
      indicate a Middle Stone Age technology comparable to assemblages of similar age
      elsewhere in Ethiopia. Studies of the mammalian, avian, and fish faunas indicate
      overall similarities to those found in the region today, with a few distinctive
      differences.

PMID- 18617220
TI  - Non-masticatory uses of anterior teeth of Sima de los Huesos individuals (Sierra
      de Atapuerca, Spain).
AB  - In this study we examine the labial and occlusal surfaces of incisors and canines
      of hominins recovered from the Sima de los Huesos (SH), middle Pleistocene site,
      in order to establish the possible extra-masticatory use of anterior teeth. We
      have compared the microwear of these fossils with microwear from the anterior
      teeth of Australian Aborigines, a population characterized by ethnographic
      evidence of the use of their teeth as a third hand. These two samples of teeth
      were microscopically analyzed using Scanning Electron Microscopy (SEM). Our
      results support the "cultural" origin of microwear observed on fossil teeth: we
      conclude that the SH hominins used their anterior teeth as a "third hand" for
      para- or extra-masticatory activities.

PMID- 18617221
TI  - Studying sulfur functional groups in Norway spruce year rings using S L-edge
      total electron yield spectroscopy.
AB  - Profiles of the major sulfur functional groups in mature Norway spruce wood
      tissue have been established for the first time. The big challenge was the
      development of a method suitable for sulfur speciation in samples with very low
      sulfur content (<100 ppm). This became possible by synchrotron X-ray absorption
      spectroscopy at the sulfur L-edge in total electron yield (TEY) detection mode
      with thin gold-coated wood slices. Functional groups were identified using sulfur
      compound spectra as fingerprints. Latewood of single year rings revealed
      metabolic plausible sulfur forms, particularly inorganic sulfide, organic
      disulfide, methylthiol, and highly oxidized sulfur. Form-specific profiles with
      Norway spruces from three different Swiss forest sites revealed high, but
      hitherto little-noticed, sulfur intensities attributable to natural heartwood
      formation and a common, but physiologically unexpected maximum around year ring
      1986 with trees from the industrialized Swiss Plateau. It is hypothesized whether
      it may have resulted from the huge reduction in sulfur emissions after 1980 due
      to Swiss policy. Comparison with total S content profiles from optical emission
      spectroscopy underlined the more accurate and temporally better resolved TEY data
      with single wood year rings and it opened novel insights into the wood cell
      chemistry.

PMID- 18617223
TI  - "Linking proteolysis to lipids".

PMID- 18617222
TI  - Mercury pollution in Guizhou, southwestern China - an overview.
AB  - Mercury (Hg) is a global pollutant and poses a worldwide concern due to its high
      toxicity. Guizhou province is recognized as a heavily Hg-polluted area in China
      due to both the special geochemical background and human activities. Here an
      integrated overview of current knowledge on the behavior of Hg in environments,
      as well as human health risk with respect to Hg contaminations in Guizhou was
      presented. Two key anthropogenic Hg emission sources in Guizhou were coal
      combustion and metals smelting, which dominantly contributed to the high levels
      of Hg in local ecosystems and high fluxes of Hg deposition. The annual Hg
      emission from anthropogenic sources ranged between 22.6 and 55.5 t, which was
      about 6.3-10.3% of current total Hg emissions in China. Meanwhile, Hg Hg-enriched
      soil in the province serves an important natural Hg emission source to the
      ambient air. The local environment of Hg mining and zinc smelting areas are
      seriously contaminated with Hg. It is demonstrated that rice growing in Hg Hg
      contaminated soil can accumulate methylmercury (MeHg) to a level to pose health
      threat to local inhabitants whose staple food is rice. Local inhabitants in Hg
      mining areas are exposed to Hg through inhalation of Hg vapor and consumption of
      rice with high level of MeHg. Rice intake is indeed the main MeHg exposure
      pathway to local inhabitants in Hg mining areas in Guizhou, which is contrary to
      the general point of view that fish and fish products are the main pathway of
      MeHg exposure to humans.

PMID- 18617224
TI  - Polysaccharides from the skin of the ray Raja radula. Partial characterization
      and anticoagulant activity.
AB  - INTRODUCTION: The polysaccharide fraction from the skin of the ray Raja radula
      was extracted, characterized and assayed for anticoagulant activity. MATERIALS
      AND METHODS: A whole polysaccharidic fraction was extracted from the skin of the
      ray Raja radula by papain digestion followed by cetylpyridinium chloride and
      ethanol precipitation and was subjected to gel chromatography and anion exchange
      chromatography, acetate cellulose electrophoresis and characterized by
      physicochemical procedures. APTT and anti Xa assays were performed to assess the
      anticoagulant activity of the polysaccharidic fractions in comparison with
      unfractionated heparin. RESULTS: Gel and anion-exchange chromatography revealed
      two negatively charged polysaccharidic populations different in both molecular
      weight and charge. Infrared spectra suggested the occurrence of uronic acids and
      acetylated hexosamines. The second polysaccharide was highly sulfated, with a
      sulfate content of approximately 29%. These data suggested that dermatan sulfate
      (DS) is the sulfate rich polysaccharide whereas hyaluronic acid (HA) is the
      polysaccharide devoid of sulfate groups. Molecular mass characterization
      indicated that their average molecular masses were 22 kDa and 85 kDa,
      respectively. The sulfated polysaccharide, i.e. presumably DS, accounted alone
      for the observed concentration-dependent anticoagulant activity which was, as
      measured by APTT, 2 to 3-fold lower than that of heparin. In addition, it had a
      significant anti-Xa activity. CONCLUSION: A major-sulfated polysaccharide, likely
      a dermatan sulfate, was extracted from the ray Raja radula skin. The results
      indicated that it exhibited a high anticoagulant activity and suggested that it
      was mediated by both heparin cofactor II and antithrombin.

PMID- 18617225
TI  - Patients with primary antiphospholipid antibody syndrome and without associated
      vascular risk factors present a normal endothelial function.
AB  - INTRODUCTION: Primary antiphospholipid antibody syndrome (PAPS) is characterized
      by venous or arterial thrombosis and positive antiphospholipid antibodies. It is
      controversial whether PAPS patients have early atherosclerosis. Endothelial
      dysfunction is an early event in the natural history of atherosclerosis. Aim of
      our study was to compare endothelial function of patients with PAPS and no
      associated risk factors with that of age- and sex-matched controls. MATERIALS AND
      METHODS: Patients with PAPS, carefully selected to exclude all known risk factors
      for cardiovascular diseases, estrogen therapy, pregnancy, intake of drugs
      affecting endothelial function, vitamins or antioxidants, were included in a case
      control study. Controls were age- (+/-5 years) and sex-matched subjects with the
      same exclusion criteria but without PAPS. Flow-mediated dilation of the brachial
      artery and some plasmatic markers of endothelial and platelet activation were
      measured. Measures are expressed as mean+/-SEM. RESULTS: Twenty cases (mean age
      42+/-4.0 years, 11 females) and 39 controls (mean age 41+/-2.9, 22 females) were
      studied. FMD was 5.7+/-0.8% in cases (95% CI: 4.1 to 7.3) and 6.8+/-0.5% (5.7 to
      7.9) in controls (p=NS). Plasma von Willebrand factor was 128+/-11.3% and 134.2+/
      16.1% in cases and controls, respectively (p=NS). Soluble P-selectin and soluble
      CD40L were 94.1+/-4.9 ng/ml and 0.7+/-0.1 ng/ml in cases and 87.7+/-4.0 ng/ml and
      1.0+/-0.2 in controls, respectively (p=NS). In a substudy, circulating progenitor
      and mature endothelial cells were comparable between the two groups. CONCLUSIONS:
      Endothelial function in patients with PAPS and no associated risk factors is
      similar to that of age- and sex- matched controls. These data suggest that the
      alterations leading to thrombosis in PAPS concern primarily the clotting system.

PMID- 18617226
TI  - The leukotriene d4 receptor antagonist, montelukast, inhibits mast cell
      degranulation in the dermis induced by water avoidance stress.
AB  - Cysteinyl leukotrienes play a part in inflammatory reactions such as asthma and
      inflammatory bowel diseases. The leukotrienes exert their actions by binding to
      and activating various receptors. Montelukast, a leukotriene receptor antagonist,
      which is used in the treatment of asthma has been shown to be effective in
      inhibiting the action or formation of leukotrienes. Many skin disorders, such as
      atopic dermatitis and psoriasis, worsen during stress and seem to be related to
      infiltration and activation of mast cells that are releasing vasoactive and pro
      inflammatory mediators. The aim of the present study was to investigate the
      effects of montelukast on the degranulation of mast cells in the dermis that is
      induced by water avoidance stress (WAS). Wistar albino rats were divided into
      four groups of 8 animals each. Control rats were injected with (1) the vehicle
      solution or (2) the montelukast solution in the absence of WAS. (3) the WAS group
      of rats was administered vehicle solution following WAS exposure for 2h daily for
      5 days. (4) The WAS+ML group was administered montelukast 10mg/kg; i.p. following
      WAS exposure for 2h daily for 5 days. Dermal mast cell numbers were determined
      with toluidine blue and tryptase immunohistochemistry and observed using a light
      microscope. Numbers of both granulated and degranulated mast cells were
      significantly increased in the WAS group when compared to control rats.
      Montelukast treatment decreased the number of both mature granulated and
      degranulated mast cells in rats subjected to WAS. In conclusion, chronic
      montelukast treatment reduced WAS-induced infiltration and activation of mast
      cells in the dermis and may provide a useful therapeutic option in stress-induced
      skin disorders.

PMID- 18617227
TI  - Dynamics of human atrial cell models: restitution, memory, and intracellular
      calcium dynamics in single cells.
AB  - Mathematical models of cardiac cells have become important tools for
      investigating the electrophysiological properties and behavior of the heart. As
      the number of published models increases, it becomes more difficult to choose a
      model appropriate for the conditions to be studied, especially when multiple
      models describing the species and region of the heart of interest are available.
      In this paper, we will review and compare two detailed ionic models of human
      atrial myocytes, the Nygren et al. model (NM) and the Courtemanche et al. model
      (CM). Although both models include the same transmembrane currents and are
      largely based on the same experimental data from human atrial cells, the two
      models exhibit vastly different properties, especially in their dynamical
      behavior, including restitution and memory effects. The CM produces pronounced
      rate adaptation of action potential duration (APD) with limited memory effects,
      while the NM exhibits strong rate dependence of resting membrane potential (RMP),
      limited APD restitution, and stronger memory, as well as delayed
      afterdepolarizations and auto-oscillatory behavior upon cessation of rapid
      pacing. Channel conductance modifications based on experimentally measured
      changes during atrial fibrillation modify rate adaptation and memory in both
      models, but do not change the primary rate-dependent properties of APD and RMP
      for the CM and NM, respectively. Two sets of proposed changes to the NM that
      yield a spike-and-dome action potential morphology qualitatively similar to the
      CM at slow pacing rates similarly do not change the underlying dynamics of the
      model. Moreover, interchanging the formulations of all transmembrane currents
      between the two models while leaving calcium handling and ionic concentrations
      intact indicates that the currents strongly influence memory and the rate
      adaptation of RMP, while intracellular calcium dynamics primarily determine APD
      rate adaptation. Our results suggest that differences in intracellular calcium
      handling between the two human atrial myocyte models are responsible for marked
      dynamical differences and may prevent reconciliation between the models by
      straightforward channel conductance modifications.

PMID- 18617229
TI  - Percutaneous transesophageal gastrotubing: alternative tube nutrition for a
      patient with a ventriculoperitoneal shunt.
AB  - BACKGROUND: We report a patient who underwent percutaneous transesophageal
      gastrotubing (PTEG), that is, nonsurgical esophagostomy under ultrasonographic
      control, as an alternative to percutaneous endoscopic gastrostomy (PEG). CASE
      DESCRIPTION: The PTEG was placed for shunt protection from inadvertent infection
      in a 29-year-old male patient in whom a ventriculoperitoneal (VP) shunt had
      previously been inserted. During the 3-year follow-up period, no complications
      associated with PTEG were experienced. CONCLUSION: Percutaneous transesophageal
      gastrotubing is a good alternative to PEG in a patient with a VP shunt. Further
      investigation concerning the risk of infection related to PTEG and PEG in VP
      shunt patients is needed.

PMID- 18617228
TI  - Middle fossa approach: microsurgical anatomy and surgical technique from the
      neurosurgical perspective.
AB  - BACKGROUND: The purpose of this study was to call attention to the subtemporal
      approach directed through the petrous apex to the IAM. We studied the
      microsurgical anatomy of the middle floor to delineate a reliable angle between
      the GSPN and the IAM to precisely localize and expose the IAM from above. A new
      technique for the elevation of middle fossa floor in an anterior-to-posterior
      direction has also been examined in cadaveric dissections and performed in
      surgery. METHODS: The microsurgical anatomy of the middle fossa floor was studied
      in 10 adult cadaveric heads (20 sides) after meatal drilling on the middle fossa.
      Five latex-injected specimens were dissected in a stepwise manner to further
      define the microsurgical anatomy of the middle fossa approach. The middle fossa
      approach is illustrated in a patient for the decompression of the facial nerve to
      demonstrate the surgical technique and limitations of bone removal. RESULTS:
      Elevation of middle fossa dura in an anterior-to-posterior direction leads to
      early identification of the GSPN, where the nerve passes under V3. The most
      reliable and easily appreciated angle to be used in localizing the IAM is between
      the IAM and the long axis of the GSPN, which is approximately 61 degrees .
      Beginning drilling the meatus medially at the petrous ridge is safer than
      beginning laterally, where the facial and vestibulocochlear nerves become more
      superficial. The cochlea anteromedially, vestibule posterolaterally, and superior
      semicircular canal posteriorly significantly limit the bone removal at the
      lateral part of the IAM. CONCLUSIONS: The surgical technique for the middle fossa
      approach which includes an anterior-to-posterior elevation of middle fossa dura
      starting from the foramen ovale and uses the angle between the IAM and the long
      axis of the GSPN to localize the meatus from above may be an alternative to
      previously proposed surgical methods.

PMID- 18617232
TI  - Use of lumbar drainage of cerebrospinal fluid for brain relaxation in occipital
      lobe approaches in children: technical note.
AB  - BACKGROUND: The purpose of this report is to describe the use of lumbar drainage
      of CSF in children to achieve brain relaxation for occipital lobe approaches with
      the need for minimal retraction. This technique of brain relaxation, widely
      reported and used in the adult neurosurgical literature, has not been documented
      by published reports in the pediatric literature. CASE DESCRIPTION: We illustrate
      this technique through the case of a 5-year-old patient who was operated on for
      an AVM of the occipital lobe through a suboccipital supratentorial approach.
      CONCLUSIONS: We confirm that lumbar drainage of CSF is an effective and safe
      technique, and an alternative to ventriculostomy placement, in accomplishing
      brain relaxation and minimal retraction in occipital lobe approaches in children.
      We discuss the advantages and disadvantages related to lumbar drain and
      ventriculostomy placement.

PMID- 18617230
TI  - Nonaneurysmal nonperimesencephalic subarachnoid hemorrhage: is it a benign
      entity?
AB  - BACKGROUND: Although the clinical profile of patients with PMN SAH is well
      documented, there are scarce data available for patients with nonaneurysmal n-PMN
      SAH. In the present study, the clinical characteristics of patients with n-PMN
      SAH were analyzed and compared with those of PMN SAH and aneurysmal SAH. METHODS:
      Patients with spontaneous SAH, in whom the initial DSA or 3-dimensional CTA
      result was normal, underwent another investigation (CTA/DSA). If the results of
      both of these were negative, a second DSA was done after 4 to 6 weeks. Patients
      in whom even the second DSA failed to reveal an aneurysm or any other vascular
      abnormality were labeled as nonaneurysmal SAH. Within this group, 2 different
      types were identified: PMN SAH and n-PMN SAH. RESULTS: There were 61 patients in
      whom the results of the first DSA and CTA were both negative. In 2 of these
      patients, an aneurysm was demonstrated at a second DSA. Seven patients died
      before a second DSA could be done. After excluding these, there were 18 patients
      with PMN SAH and 34 with n-PMN SAH. There was no mortality in these patients; and
      at a mean follow-up of 1.8 years, all patients with PMN SAH and 94.1% of patients
      with n-PMN SAH had a good outcome. Associated comorbid illnesses were more
      frequent in patients with PMN SAH and n-PMN SAH as compared with the aneurysmal
      SAH patients. CONCLUSIONS: Once an aneurysm is definitely excluded, patients with
      n-PMN SAH have a good outcome, and like PMN SAH, have a benign clinical course.
      However, a second DSA is mandatory to avoid missing an aneurysm or any other
      vascular lesion.

PMID- 18617234
TI  - Erosion of physician autonomy and public respect for the profession.

PMID- 18617237
TI  - The expression of thyroid hormone receptor isoforms in human astrocytomas.
AB  - BACKGROUND: Thyroid hormone plays a major role in normal mammalian brain
      maturation and affects the development of astrocytes. The expression of TR
      isoforms has been studied in different neoplasias. Increasing evidence has
      suggested that aberrant expression of TR isoforms could be associated with
      tumorigenesis. However, little was studied about the expression of TR isoforms in
      human astrocytomas. METHODS: In this study, RT-PCR was used to examine the
      expression of human TR isoforms in 34 human astrocytoma samples. RESULTS: We
      compared the TR expression between low grade (WHO grade II) and high grade (WHO
      grade III and IV). The frequency of TRalpha1 or TRalpha2 expression significantly
      decreased with the grade of malignancy (P=.005 and P=.043, respectively).
      However, the frequency of TRbeta1 expression significantly increased with the
      grades of malignancy astrocytomas (P=.017). CONCLUSIONS: Our study demonstrated
      for the first time that TR isoforms are indeed expressed in human astrocytomas.
      The expression of TR isoforms is correlated to the malignancy grading of
      astrocytomas. Our result provides insight into the potential use of hormonal
      therapy for brain tumors that overexpress or underexpress TRs.

PMID- 18617238
TI  - Comparison of pressure effects on adjacent disk levels after 2-level lumbar
      constructs: fusion, hybrid, and total disk replacement.
AB  - BACKGROUND: With increasing advocacy for the use of TDR procedure as a surgical
      alternative to fusion in the management of lumbar DDD, intradiskal pressures at
      the adjacent levels of spine have generated considerable interest. The common
      belief is that adjacent-level disk pressures will be lower after a TDR as opposed
      to conventional fusion. The aim of this study is to present the effect of
      different constructs on adjacent-level disk pressures in lumbar spine. We
      hypothesized that the adjacent-segment disk pressures after 1- and 2-level TDR
      and/or a fusion-TDR hybrid procedure will show significant variance within
      physiological range of motion. METHODS: Six adult spine segments T12-S1 with
      intact ligaments were harvested from cadavers and held firmly in a specially
      designed fixture. Intradiskal pressures, in motions of flexion, extension, and
      lateral bending, at L2-L3 and L3-L4 were measured using needle transducers after
      2-level TDR L4 through S1, hybrid procedure, and 2-level fusion L4-S1 with
      femoral ring allograft and pedicle screws. RESULTS: The pressures with lateral
      bending were not significantly lower than those with flexion and extension at
      both levels (P = .18). Although TDR and hybrid specimens recorded slightly lower
      pressures specifically during lateral bending, no statistical difference in
      pressures could be detected when movements were combined with various procedures.
      CONCLUSION: Contrary to the assumed hypothesis, the pressures at the adjacent
      level disks (L3-4 and L2-3) did not depend upon the stabilization procedure (2
      level disk replacement, hybrid, or 2-level fusion) performed after 2-level
      diskectomy in the lumbosacral spine.

PMID- 18617239
TI  - Use of frameless stereotactic computed tomography venography for intraoperative
      localization of dural arterial venous fistulas: case report.
AB  - BACKGROUND: The following technical case report illustrates the use of multiple
      imaging modalities including 3D CTV with frameless stereotactic navigation for
      intraoperative planning and localization for surgical obliteration of a cranial
      dAVF with leptomeningeal drainage. CASE DESCRIPTION: This 65-year-old man
      presented with an asymptomatic occipital dAVF with leptomeningeal drainage. In
      addition to cerebral angiography, a CTV with 3D reconstruction was performed,
      which provided excellent visualization of the dAVF and clarified its pattern of
      drainage. The dAVF was supplied by a middle meningeal artery branch that drained
      into an occipital cortical vein, which then retrograde filled the vein of Labbe.
      Frameless stereotactic navigation with the imported CTV images was used to plan
      the craniotomy and to localize the leptomeningeal draining vein and vein of
      Labbe. The draining vein of the fistula was successfully ligated and divided
      while preserving flow in the vein of Labbe. Postoperative angiogram demonstrated
      complete obliteration of the dAVF. CONCLUSION: Integration of a 3D reconstructed
      CTV with conventional angiographic information optimized our surgical
      understanding of the spatial anatomy of this dAVF and its pattern of venous
      drainage. Applying the CTV with frameless stereotaxy allowed for safe
      obliteration of the dAVF while preserving the vein of Labbe.

PMID- 18617242
TI  - Re: international neurosurgery-not a luxury, but a need!

PMID- 18617243
TI  - Acanthamoeba infection in an interhemispheric ependymal cyst: a case report.
AB  - BACKGROUND: Free-living amoebae are known to cause fatal granulomatous
      encephalitis in immunocompromised individuals. They are also known to present as
      multifocal parenchymal lesions, pseudotumoral lesions, meningeal exudates,
      hemorrhagic infarcts, and necrosis in the brain. However, Acanthamoeba infection
      in an intracranial ependymal cyst has not been reported in the literature. CASE
      DESCRIPTION: A 25-year-old immunocompetent man presented with a suspected
      interhemispheric arachnoid cyst. The cyst fluid turned out be infected with
      Acanthamoeba. The patient was treated successfully with decompression of the cyst
      with combination chemotherapy. CONCLUSION: Acanthamoeba may cause secondary
      infection in an underlying brain cyst. A suspicion of such an infection must be
      raised in the presence of altered nature of CSF consistency. The aggressive
      chemotherapy is the only hope for favorable outcome. The dilemmas associated with
      the diagnosis and treatment are further discussed.

PMID- 18617245
TI  - Acute ischemic complications after therapeutic parent artery occlusion with
      revascularization for complex internal carotid artery aneurysms.
AB  - BACKGROUND: Parent artery occlusion (PAO) is an alternative surgical strategy for
      complex internal carotid artery (ICA) aneurysms, which are unclippable because of
      their anatomical structures, including a broad neck, fragile dome, critical
      branch, and cavernous sinus location. Despite revascularization, ischemic
      complications occur after the PAO because of several factors, such as
      hypoperfusion, embolism, and perforator impairment. METHODS: Acute ischemic
      complications and their mechanisms were analyzed in a consecutive series of 32
      patients presenting with complex ICA aneurysms treated by PAO. RESULTS: Fourteen
      ruptured and 18 unruptured aneurysms were located in the cavernous sinus (n = 16)
      and paraclinoid portion (n = 16). Preoperative balloon test occlusion was
      performed to investigate ischemic tolerance and to select the bypass method in 24
      cases. An extracranial-intracranial bypass was constructed using the superficial
      temporal artery in 17, and a saphenous vein graft was done in 12 cases. Although
      postoperative hypoperfusion was prevented by revascularization based on the
      balloon test occlusion, acute ischemic complications due to perforator occlusion
      and thromboembolism were observed in 10 cases after the surgery. Five cases
      presented with impairment of perforating branches adjacent to the occluded parent
      artery, resulting in prolonged neurologic deterioration. CONCLUSION: The distal
      location of ICA aneurysms is a risk factor for the perforator impairment, when
      treated by PAO, and PAO by clip placement is preferred to endovascular coiling to
      prevent of perforator impairment.

PMID- 18617246
TI  - Occlusion of neck remnant in experimental rat aneurysms after treatment with
      platinum- or polyglycolic-polylactic acid-coated coils.
AB  - BACKGROUND: Neck remnants and aneurysm recurrences are marked limitations of
      endovascular treatment of cerebral artery aneurysms. We compared the evolution of
      neck remnants of experimental arterial rat aneurysms after treatment with either
      platinum- or PGLA-coated coils. METHODS: We created 20 standard-size aneurysms in
      the abdominal aortas of male Wistar rats. Aneurysms were embolized with either
      PGLA-coated coils or platinum coils, with care taken to leave a neck remnant.
      Neck remnant size and shape was closely monitored to detect progressive
      enlargement or occlusion. Using a 4.7 T MR scanner, we acquired high-resolution
      MR images 6 times during the 4-week follow-up. For quantitative measurements, we
      used a high-resolution 3D-TOF angiography sequence. Results were verified by
      endoscopy and histology. RESULTS: Aneurysms treated with PGLA coils showed, on
      average, a 12.9% reduction of neck remnant size (P = .044) and significant
      disappearance of dog ears, the blood-filled spaces between coils and aneurysm
      wall. The aneurysms treated with platinum coils lacked these changes. In
      endoscopy, neointima was found to cover both PGLA and platinum coils but was more
      often incomplete or translucent in the platinum group. In histology, thrombus
      organization and inflammatory cell infiltration were higher with PGLA.
      CONCLUSION: Use of PGLA-coated coils was followed by a moderate progressive
      reduction of the neck remnant size and a better angiographic outcome, seen as
      disappearance of dog ears during follow-up. The rat model proved to be suitable
      for comparison of different coil types.

PMID- 18617248
TI  - Early experiences with a novel (robot hand) technique in the course of
      microneurosurgery.
AB  - BACKGROUND: The physiologic tremor may cause difficulties in microsurgery, in
      spite of using armrest. The new (robot hand) technique consists of the I-III
      finger support, which holds the instruments on Bethlehem (ANDAN BT, Budapest,
      Hungary) bridge above the operation area, which reduces the tremor at the end of
      the instruments. METHODS: Exact measurement of tremor reduction was performed.
      Last year, 23 microsurgical cases were operated on by the robot hand technique.
      RESULTS: The tremors of the operating hand and the number of complications have
      decreased effectively. CONCLUSION: By this technique, the microsurgical work has
      become more precise.

PMID- 18617249
TI  - Self-drilling anchor screws for dural tenting sutures: technical note.
AB  - BACKGROUND: Dural tenting sutures are difficult to place in the case of keyhole
      surgery and other craniotomies exposing the temporal base and sphenoid ridge
      because of difficulty in making small drill holes along the bone edge. METHODS:
      The technical difficulty is solved by using a self-drilling anchor screw. A 4-mm
      self-drilling titanium screw is fixed loosely to either the cortical surface or
      the cancellous bone of the bone edge to anchor dural tenting sutures. RESULTS:
      The present technique allowed easy placement of dural tenting sutures and
      efficient epidural hemostasis under the bone edge in more than 100 craniotomies.
      CONCLUSIONS: The anchor screw technique allows easy placement of dural tenting
      sutures along the bone edge in the craniotomy with a limited exposure.

PMID- 18617252
TI  - Profiles in volunteerism from India to Peru as a neurosurgeon volunteer.

PMID- 18617255
TI  - Digital photography using the intraoperative microscope in neurosurgery.
AB  - BACKGROUND: The ability to obtain high-resolution intraoperative microscopic
      images has previously been reserved for those with expensive microscope-mounted
      cameras, standard optical or digital. The authors review the technique and
      utility of intraoperative digital photography through the microscope. METHODS: We
      present a simple technique for obtaining high-quality digital micrographs without
      the need for special equipment that may be expensive, complex, and/or dedicated
      to a specific operative microscope. RESULTS: Images and video may be obtained
      using a standard personal digital camera. CONCLUSIONS: Use of the technique
      presented provides the surgeon with the ability to acquire high-quality
      intraoperative microphotographs and video.

PMID- 18617257
TI  - The effect of a pedometer-based physical activity intervention on sitting time.
AB  - OBJECTIVE: To assess whether the "10,000 Steps Ghent" intervention had any effect
      on self-reported sitting time. METHODS: A multi-strategy community-based
      intervention was implemented in 2005 to promote physical activity (PA) to adults
      living in Ghent, Belgium. In 2005, 648 randomly selected participants (aged 25 to
      75) from the intervention community Ghent and 592 from a comparison community,
      completed the International Physical Activity Questionnaire (IPAQ) and a
      pedometer log. Of these, 440 intervention participants and 426 comparison
      participants completed the follow-up measurements in 2006. RESULTS: A decrease of
      12 min in total daily sitting time was found in the intervention community,
      compared with an increase of 18 min/day in the comparison community (F=9.5,
      p=0.002). The effect was seen for both weekday (p=0.044) and weekend day
      (p<0.001) sitting times. In the intervention community, total daily sitting time
      decreased more in the participants who increased their step counts (-18 min/day;
      t=2.5; p=0.012), than in those who did not (no change; t=0.8, ns). CONCLUSIONS:
      After 1 year of intervention, total, weekday, and weekend day sitting times were
      reduced in the intervention community, while sitting time increased in the
      comparison community.

PMID- 18617258
TI  - Advancing dental implant surface technology--from micron- to nanotopography.
AB  - Current trends in clinical dental implant therapy include use of endosseous
      dental implant surfaces embellished with nanoscale topographies. The goal of this
      review is to consider the role of nanoscale topographic modification of titanium
      substrates for the purpose of improving osseointegration. Nanotechnology offers
      engineers and biologists new ways of interacting with relevant biological
      processes. Moreover, nanotechnology has provided means of understanding and
      achieving cell specific functions. The various techniques that can impart
      nanoscale topographic features to titanium endosseous implants are described.
      Existing data supporting the role of nanotopography suggest that critical steps
      in osseointegration can be modulated by nanoscale modification of the implant
      surface. Important distinctions between nanoscale and micron-scale modification
      of the implant surface are presently considered. The advantages and disadvantages
      of nanoscale modification of the dental implant surface are discussed. Finally,
      available data concerning the current dental implant surfaces that utilize
      nanotopography in clinical dentistry are described. Nanoscale modification of
      titanium endosseous implant surfaces can alter cellular and tissue responses that
      may benefit osseointegration and dental implant therapy.

PMID- 18617259
TI  - Induced stepwise conformational change of human serum albumin on carbon nanotube
      surfaces.
AB  - Non-covalent adsorption of proteins onto carbon nanotubes is important to
      understand the environmental and biological activity of carbon nanotubes as well
      as their potential applications in nanostructure fabrication. In this study, the
      adsorption dynamics and features of a model protein (the A sub-domain of human
      serum albumin) onto the surfaces of carbon nanotubes with different diameters
      were investigated out by molecular dynamics simulation. The adsorption behaviors
      were observed by both trajectory and quantitative analyses. During the adsorption
      process, the secondary structures of alpha-helices in the model protein were
      slightly affected. However, the random coils connecting these alpha-helices were
      strongly affected and this made the tertiary structure of protein change. The
      conformation and orientation selection of the protein were induced by the
      properties and the texture of surfaces indicated by the interaction curve. In
      addition, the stepwise adsorption dynamics of these processes are found. The
      mechanism of induced stepwise conformational change of protein on carbon nanotube
      surfaces would be helpful to better understand the protein-surface interaction at
      the molecular level.

PMID- 18617260
TI  - Induction of osteoblast differentiation phenotype on poly(L-lactic acid)
      nanofibrous matrix.
AB  - Thin sheets of nanofibrous (NF) poly(L-lactic acid) (PLLA) matrix were fabricated
      using a novel phase separation method, mimicking the structure of natural
      collagen fibers. In this study, the cell morphology, cytoskeleton and adhesion
      structure, proliferation and differentiation were investigated on NF PLLA matrix
      using an osteoblast cell line model. Scanning electron microscopy revealed that
      the MC3T3-E1 cells took a more rounded shape on NF matrix, with abundant
      interactions with nanofibers. There were no long dense stress fibers or typical
      focal adhesion structures formed on NF matrix. In consistence with the flat cell
      morphology and abundant focal adhesions, the cell proliferation was faster on
      flat PLLA films. With the addition of ascorbic acid (AA), cells were induced to
      differentiate both on NF matrix and flat films. Cells on NF matrix exhibited an
      enhanced osteoblast differentiation phenotype, with dramatically higher bone
      sialoprotein (BSP) gene expression (two orders of magnitude higher) and
      significantly higher alkaline phosphatase (ALP) activities. Strikingly, even
      without the addition of AA, thus no natural collagen fibers deposited into the
      matrix, the BSP gene expression was still highly up-regulated on NF matrix,
      showing a direct effect of PLLA nanofibers on BSP gene expression. Enhanced BSP
      gene expression was correlated with the down-regulation of the small GTPase RhoA
      activities. Inhibition of RhoA effector ROCK induced BSP gene expression of cells
      in AA-free medium on flat PLLA films. These results suggest that the nanofibers
      promote the differentiation of osteoblasts likely through RhoA-Rock signaling
      pathway.

PMID- 18617261
TI  - Somatostatin as a regulator of first-trimester human trophoblast functions.
AB  - We have tested the hypothesis that human early trophoblast is a target for
      somatostatin (SRIF) regulatory actions. We report for the first time that SSTR2A
      and 2B transcripts and proteins are present in first-trimester human chorionic
      villi and the trophoblast-derived HTR-8/SVneo and JAR cells. In both cell lines,
      SSTR are functional since SRIF inhibits cyclic AMP pathway, stimulates
      arachidonic acid release and enhances cell proliferation. Moreover, in HTR
      8/SVneo cells, considered a good model of first-trimester EVT, SRIF also enhances
      migration. An involvement of the cyclic AMP pathway in mediating SRIF effects on
      proliferation and migration is suggested. Our data support the idea that SRIF
      regulates early trophoblast functions mainly through an interaction with SSTR2.

PMID- 18617262
TI  - Vasoactive intestinal peptide-induced neuritogenesis in neuroblastoma SH-SY5Y
      cells involves SNAP-25.
AB  - Vasoactive intestinal peptide (VIP) is a neuropeptide known to regulate
      proliferation and differentiation in normal and tumoral cells. We previously
      reported that VIP induced neuritogenesis in human neuroblastoma SH-SY5Y cells
      cultured in serum-free medium. This neuritogenesis was associated with a
      regulated expression of neuronal cytoskeleton markers. To further characterize
      the neuroblastic cell differentiation induced by VIP in human SH-SY5Y cells, we
      investigated expression of synaptosomal-associated protein of 25 kDa (SNAP-25), a
      protein implicated in exocytosis associated with different processes, including
      neurite outgrowth. Western immunoblotting and real-time RT-PCR analyses revealed
      that VIP increased expression of the SNAP-25 protein and the level of both SNAP
      25a and SNAP-25b mRNA isoforms. Immunofluorescence experiments indicated that
      SNAP-25 was mainly located in neurites and at the plasma membrane in SH-SY5Y
      cells treated with VIP. RNA interference experiments demonstrated that SNAP-25
      was involved in VIP-induced neuritogenesis. In conclusion, SNAP-25 is up
      regulated and implicated in neuritogenesis in human neuroblastoma SH-SY5Y cells
      treated with the neuropeptide VIP.

PMID- 18617263
TI  - The behavioural and electrophysiological effects of CRF in rat frontal cortex.
AB  - Corticotropin releasing factor (CRF) is a neuropeptide widely distributed in the
      brain. The role of CRF in the behavioural activity and modulation of anxiety
      states in several brain structures has been well documented, but its function in
      the cerebral cortex still remains unknown. The aim of our study was to
      investigate the effect of CRF injected bilaterally into rat frontal cortex on the
      locomotor and exploratory activity and anxiety of rats. We also examined the
      effect of CRF on extracellularly recorded field potentials in rat frontal
      cortical slices in vitro. Behavioural experiments showed that CRF in doses of
      0.05, 0.1, 0.2 microg/1 microl/site decreased locomotor and exploratory activity
      during a 40-min session in the open field test. In the elevated plus-maze test,
      CRF in a dose of 0.2 microg/1 microl/site produced a significant anxiolytic-like
      effect, which was prevented by CRF receptor antagonists (alpha-helicalCRF(9-41)
      and NBI 27914). Electrophysiological experiments showed that CRF-induced a
      transient depression of field potentials in slices partly disinhibited by GABA(A)
      and GABA(B) receptors antagonists. The blockade of NMDA receptors prevented the
      occurrence of that effect. The obtained results suggest that CRF may have
      anxiolytic-like effects in the frontal cortex. Moreover, the peptide inhibits
      locomotor and exploratory activity and depresses excitatory synaptic transmission
      in a NMDA receptor-dependent manner.

PMID- 18617264
TI  - The protective effects of religiosity on maladjustment among maltreated and
      nonmaltreated children.
AB  - OBJECTIVE: The aim of this study was to investigate the role of child religiosity
      in the development of maladaptation among maltreated children. METHODS: Data were
      collected on 188 maltreated and 196 nonmaltreated children from low-income
      families (ages 6-12 years). Children were assessed on religiosity and depressive
      symptoms, and were evaluated by camp counselors on internalizing symptomatology
      and externalizing symptomatology. RESULTS: Significant interactions indicated
      protective effects of religiosity. Child reports of the importance of faith were
      related to lower levels of internalizing symptomatology among maltreated girls
      (t=-2.81, p<.05). Child reports of attendance at religious services were
      associated with lower levels of externalizing symptomatology among nonmaltreated
      boys (t=1.94, p=.05). CONCLUSION: These results suggest that child religiosity
      may largely contribute to stress coping process among maltreated and
      nonmaltreated children from low-income families. The results also indicate that
      the protective roles of religiosity varied by risk status and gender. PRACTICAL
      IMPLICATIONS: The results indicate that a range of child religiosity behaviors
      and practices can be assessed in translational prevention research. It is
      recommended that healthcare professionals, psychologists, and social workers
      working with maltreated children and their families assess for salience of
      religiosity and may encourage them to consider the role religiosity plays in the
      development of prevention and intervention programs to alleviate distress and
      enhance stress coping.

PMID- 18617265
TI  - Trauma-related predictors of deontic reasoning: a pilot study in a community
      sample of children.
AB  - OBJECTIVE: Deontic reasoning (i.e., reasoning about duties and obligations) is
      essential to navigating interpersonal relationships. Though previous research
      demonstrates links between deontic reasoning abilities and trauma-related factors
      (i.e., dissociation, exposure to multiple victimizations) in adults, studies have
      yet to examine deontic reasoning abilities in children exposed to trauma. Given
      that social and safety rules (exemplars of deontic reasoning rules) may appear
      arbitrary for children in the face of trauma exposure, particularly interpersonal
      violence perpetrated by adults (i.e., caregivers, close relatives), we predicted
      that the ability to detect violations of these rules would vary as a function of
      trauma exposure type (no, non-interpersonal, and interpersonal). Additionally,
      given previous research linking dissociation and deontic reasoning in adults, we
      predicted that higher levels of dissociation would be associated with more errors
      in deontic problems. METHODS: Children exposed to interpersonal violence (e.g.,
      sexual abuse by an adult family member, witnessing domestic violence, or physical
      abuse in the home) were compared to children exposed to non-interpersonal trauma
      (e.g., motor vehicle accident, natural disaster) or no trauma on their ability to
      detect violations of deontic and descriptive rules in a Wason Selection Task and
      assessed for their level of dissociative symptoms. RESULTS: Dissociation (but not
      trauma exposure type) predicted errors in deontic (but not descriptive) reasoning
      problems after controlling for estimated IQ, socio-economic status, and
      children's ages. CONCLUSIONS: The current study provides preliminary evidence
      that deontic reasoning is associated with dissociation in children. This pilot
      study points to the need for future research on trauma-related predictors of
      deontic reasoning. PRACTICE IMPLICATIONS: Deontic rules are essential to
      navigating interpersonal relationships; errors detecting violations of deontic
      rules have been associated with multiple victimizations in adulthood. Future
      research on violence exposure, dissociation, and deontic reasoning in children
      may have important implications for intervention and prevention around
      interpersonal functioning and later interpersonal risk.

PMID- 18617266
TI  - Fungal dye decolourization: recent advances and future potential.
AB  - Dyes released by the textile industries pose a threat to the environmental
      safety. Recently, dye decolourization through biological means has gained
      momentum as these are cheap and can be applied to wide range of dyes. This review
      paper focuses on the decolourization of dye wastewaters through fungi via two
      processes (biosorption and bioaccumulation) and discusses the effect of various
      process parameters like pH, temperature, dye concentration etc. on the dye
      removing efficiency of different fungi. Various enzymes involved in the
      degradation of the dyes and the metabolites thus formed have been compiled.
      Genetic manipulations of microorganisms for production of more efficient
      biological agents, various bioreactor configurations and the application of
      purified enzymes for decolourization, which constitute some of the recent
      advances in this field, have also been reviewed. The studies discussed in this
      paper indicate fungal decolourization has a great potential to be developed
      further as a decentralized wastewater treatment technology for small textile or
      dyeing units. However, further research work is required to study the toxicity of
      the metabolites of dye degradation and the possible fate of the utilized biomass
      in order to ensure the development of an eco-friendly technology.

PMID- 18617268
TI  - Development of rat antigen-presenting cells from pluripotent ecto-mesenchymal
      stem cells in vitro and in vivo.
AB  - Dendritic cells (DC) are specialized cells that capture and present antigen to T
      cells. Recent advances have been made in understanding their origin,
      heterogeneity, and the signals that induce their migration and maturation
      resident microglia are antigen-presenting cells (APC) involved in stimulation or
      reactivation of CNS-targeted T cells. Generation of DC from microglia, as
      demonstrated ex vivo, may support GM-CSF-driven differentiation of brain DC from
      local, likely, microglial progenitors. Here, we report the establishment of long
      term cultures of rat ecto-mesenchymal stem cells (EMSCs) using specific
      supplemented media for induction. These EMSCs share some morphological
      characteristics and the allostimulatory capacity of classical DCs, and when
      transplanted into the brain using a rat glioma model survive within the cortex,
      and are morphologically and phenotypically similar to microglia over 7 days. Our
      findings related to the development and differentiation of microglial progenitors
      support the view that microglia are derived prenatally from mesodermal
      progenitors that are distinct from monocytes.

PMID- 18617267
TI  - APE/Ref-1 makes fine-tuning of CD40-induced B cell proliferation.
AB  - Apurinic/apyrimidinic endonuclease-1/Redox factor-1, a multifunctional DNA base
      excision repair and redox regulation enzyme, plays an important role in oxidative
      signalling, transcription factor regulation, and cell cycle control. Recently, we
      have demonstrated that following the triggering of CD40 on B cells, APE/Ref-1
      translocates from the cytoplasm to the nucleus and regulates the activity of B
      cell-specific transcription factors. In the present paper we investigate whether
      APE/Ref-1 plays a role in controlling CD40-mediated B cell proliferation too. We
      demonstrate a concurrent increase in proliferation and decrease in apoptosis of
      primary mouse B cells activated by CD40 cross-linking and transfected with
      functional APE/Ref-1 antisense oligonucleotide. Moreover, we provide evidence
      that a redox-mediated signalling mechanism is involved in this process and we
      propose that APE/Ref-1, controlling the intracellular redox state, may also
      affect the cell cycle by inducing nucleus-cytoplasm redistribution of p21.
      Together, these findings suggest that APE/Ref-1 could act as a negative regulator
      in an adaptive response to elevated ROS levels following CD40 cross-linking.
      Considering the important role of ROS and APE/Ref-1 in CD40-mediated B cell
      proliferation, our data will contribute to understand the mechanisms of tumor
      escape and suggest APE/Ref-1 as a novel target for tumor therapeutic approaches.

PMID- 18617269
TI  - Nationwide study of invasive Pseudomonas aeruginosa infection in Norway:
      importance of underlying disease.
AB  - OBJECTIVE: Pseudomonas aeruginosa is an opportunistic pathogen that may cause
      invasive disease. We describe the epidemiology of invasive P. aeruginosa
      infection in Norway and identify associated clinical factors. METHODS: All
      patients with invasive P. aeruginosa and Pseudomonas not identified at the
      species level (Pseudomonas spp.) in Norway 1992-2002 were included. Detailed
      information was collected for all cases during 1999-2002. Population and health
      institution statistics were obtained from national databases. RESULTS: In 1999
      2002 the incidence rate was 3.16 per 100 000 person-years at risk or 0.20 per
      1000 hospital stays. For hospital-acquired infection the rate was 671 per 100 000
      person-years as compared with 1.13 for community-acquired infection, and 37 in
      nursing homes. The highest risk for invasive Pseudomonas disease was found in
      patients with malignant neoplasms of lymphoid and haematopoietic tissue (risk per
      1000 hospital stays 1.9; 95% CI 1.5-2.3) and other diseases of blood and blood
      forming organs (2.2; 95% CI 1.2-3.7). The case fatality rate was 35%.
      CONCLUSIONS: The incidence of invasive P. aeruginosa infection in this population
      based study was much lower than in most single-hospital studies. The nationwide
      study design and prudent antibiotic use may explain some of the difference.
      Infection risk is strongly associated with certain underlying diseases.

PMID- 18617270
TI  - An alternative perspective on "semantic P600" effects in language comprehension.
AB  - The literature on the electrophysiology of language comprehension has recently
      seen a very prominent discussion of "semantic P600" effects, which have been
      observed, for example, in sentences involving an implausible thematic role
      assignment to an argument that would be a highly plausible filler for a different
      thematic role of the same verb. These findings have sparked a discussion about
      underlying properties of the language comprehension architecture, as they have
      generally been viewed as a challenge to established models of language processing
      and specifically to the notion that syntax precedes semantics in the
      comprehension process. In this paper, we review the literature on semantic P600
      effects and discuss a number of challenges--both conceptual and empirical--to
      existing approaches in this domain. We then provide a new perspective on these
      effects by showing how they can be derived within an independently motivated,
      hierarchically organised neurocognitive model of language comprehension in which
      syntactic structuring precedes argument interpretation (the extended Argument
      Dependency Model, eADM; Bornkessel and Schlesewsky, 2006). In addition to
      straightforwardly deriving the phenomenon of a "semantic P600," the basic
      architectural properties of the eADM account for existing empirical puzzles
      within the semantic P600 literature.

PMID- 18617272
TI  - Characterization of an antibody panel for immunohistochemical analysis of canine
      muscle cells.
AB  - Immunohistochemistry is an indispensable tool in the assessment and
      characterization of lineage-specific differentiation of grafted cells in cell
      based-therapy. This strategy is under investigation for the treatment of many
      muscle disorders and different animals such as dogs are used as models to study
      the tissue regeneration. The aim of the present study was to characterize an
      antibody panel for the analysis of canine muscle cells, useful in routinely
      processed formalin-fixed paraffin-embedded tissues. Overall, 12 antibodies (8
      mouse monoclonal and 4 goat polyclonal), validated for use on human tissues
      tested for cross-reactivity on canine smooth muscle (bladder, intestine, and
      uterus), skeletal muscle and heart. Specific staining was achieved with eight
      antibodies, of which six were cytoplasmic markers (desmin, HDAC8, MHC, SMA,
      Troponin I and Troponin T) and two were cardiac nuclear markers (GATA-4 and Nkx
      2.5). This antibody panel may be useful not only for the evaluation of cell-based
      therapies in muscle disorders, but also for the evaluation of canine soft tissue
      neoplasms in veterinary pathology.

PMID- 18617271
TI  - Course of suicide ideation and predictors of change in depressed older adults.
AB  - BACKGROUND: Rates of suicide among older adults in the United States are higher
      than that of other age groups. Therefore, it is critically important to deepen
      understanding of the processes that drive suicide risk among at-risk older
      patients. To this end, we examined the longitudinal course of suicide ideation in
      a sample of treatment-seeking depressed adults 60 years of age or older. METHODS:
      Secondary analyses were conducted with a longitudinal dataset including 343 older
      adults seeking treatment for depression in the context of a naturalistic
      treatment setting. Participants completed assessments of depressive symptoms and
      thoughts of suicide every three months for one year. Multi-level mixed models
      were used to examine the trajectory of suicide ideation over five waves. RESULTS:
      Depressive symptoms contributed significantly to change in thoughts of suicide
      early in treatment for depression. Age-related differences were also observed,
      such that increasing age was associated with significantly greater reports of
      suicide ideation. LIMITATIONS: Use of a single measure to ascertain severity of
      depressive symptoms and thoughts of suicide. CONCLUSIONS: Clinicians should
      expect to see the most pronounced decrease in thoughts of suicide during the
      first two months of depression treatment for older adults. Further, clinicians
      should be especially vigilant to monitor suicide ideation for adults, with
      increasing vigilance for those at more advanced ages.

PMID- 18617273
TI  - Differential host gene expression in cells infected with highly pathogenic H5N1
      avian influenza viruses.
AB  - In order to understand the molecular mechanisms by which different strains of
      avian influenza viruses overcome host response in birds, we used a complete
      chicken genome microarray to compare early gene expression levels in chicken
      embryo fibroblasts (CEF) infected with two avian influenza viruses (AIV),
      A/CK/Hong Kong/220/97 and A/Egret/Hong Kong/757.2/02, with different replication
      characteristics. Gene ontology revealed that the genes with altered expression
      are involved in many vital functional classes including protein metabolism,
      translation, transcription, host defense/immune response, ubiquitination and the
      cell cycle. Among the immune-related genes, MEK2, MHC class I, PDCD10 and Bcl-3
      were selected for further expression analysis at 24 hpi using semi-quantitive RT
      PCR. Infection of CEF with A/Egret/Hong Kong/757.2/02 resulted in a marked
      repression of MEK2 and MHC class I gene expression levels. Infection of CEF with
      A/CK/Hong Kong/220/97 induced an increase of MEK2 and a decrease in PDCD10 and
      Bcl-3 expression levels. The expression levels of alpha interferon (IFN-alpha),
      myxovirus resistance 1 (Mx1) and interleukin-8 (IL-8) were also analyzed at 24
      hpi, showing higher expression levels of all of these genes after infection with
      A/CK/Hong Kong/220/97 compared to A/Egret/Hong Kong/757.2/02. In addition,
      comparison of the NS1 sequences of the viruses revealed amino acid differences
      that may explain in part the differences in IFN-alpha expression observed.
      Microarray gene expression analysis has proven to be a useful tool on providing
      important insights into how different AIVs affect host gene expression and how
      AIVs may use different strategies to evade host response and replicate in host
      cells.

PMID- 18617274
TI  - Toll-like receptors and their role in host resistance to Toxoplasma gondii.
AB  - Toxoplasma gondii and other apicomplexan parasites are widely distributed
      obligate intracellular protozoa. A critical host mediator produced in response to
      T. gondii infection is IL-12. This cytokine is synthesized by dendritic cells,
      macrophages and neutrophils and plays a pivotal role in the production of IFN
      gamma, which in turn activates anti-microbial effector cells. In the past several
      years, many of the receptors and signaling pathways that link pathogen detection
      to induction of IL-12 have been identified and characterized. Among these
      receptors the Toll-like receptor (TLR) family can recognize all classes of
      pathogens and induce different types of immune responses. In the following
      review, I summarize the evidence for specific TLR function in host resistance to
      T. gondii.

PMID- 18617275
TI  - The expression of TNF-alpha receptors 1 and 2 on peripheral blood mononuclear
      cells in chronic inflammatory demyelinating polyneuropathy.
AB  - The proportion of peripheral blood mononuclear cells (PBMCs) expressing TNF-alpha
      and its receptors (TNFR1, TNFR2) and the serum concentrations of its soluble
      forms were analyzed by FACS and ELISA in the patients with chronic inflammatory
      demyelinating polyneuropathy (CIDP) and in controls. Elevated levels of TNFR2
      were observed on blood T cells in CIDP and idiopathic polyneuropathy. Low levels
      of TNFR1 were detected on monocytes in the subgroup of patients with CIDP
      examined after treatment with intravenous immunoglobulin. However, the
      proliferative activity of PBMCs in CIDP was not influenced by soluble recombinant
      TNFR1. Our limited data suggested the exact role of TNF-alpha and its receptors
      need to study further in CIDP, as well as in idiopathic neuropathies.

PMID- 18617276
TI  - Primary treatment of pediatric plunging ranula with nonsurgical sclerotherapy
      using OK-432 (Picibanil).
AB  - OBJECTIVE: Although surgery is the first choice of therapy for plunging ranula,
      it is associated with technical difficulties, morbidity and recurrence. Plunging
      ranula may be also primarily treated with nonsurgical sclerotherapy, but there is
      little experience in pediatric patients. We, therefore, assessed the efficacy of
      OK-432 sclerotherapy for pediatric plunging ranula. METHODS: Nine children with
      plunging ranula were prospectively treated with intracystic injections of OK-432.
      At the outpatient clinic, the ranula was punctured in the neck and aspirated
      mucus was replaced with 0.1-0.2mg OK-432 solution. The size of the ranula was
      compared before and after sclerotherapy. RESULTS: Total or nearly total shrinkage
      was observed in 6 of 9 patients; marked reduction (>50% of original size) in 2;
      and partial reduction (<50% of original size) in 1. At a mean follow-up of 26
      months after last sclerotherapy, recurrence was observed in only 1 patient; this
      patient showed complete response after reinjection of OK-432 solution. No
      significant complications were observed, with only fever and mild local pain
      observed in 4 patients for 2-4 days after treatment. CONCLUSIONS: OK-432
      sclerotherapy is safe and effective in the treatment of pediatric plunging
      ranula. Sclerotherapy may become a primary treatment modality prior to surgery.

PMID- 18617277
TI  - Neuroinflammation and synaptic plasticity: theoretical basis for a novel, immune
      centred, therapeutic approach to neurological disorders.
AB  - The fascinating capacity that the central nervous system (CNS) has for encoding
      and retaining memories is thought to be based on activity-dependent forms of
      synaptic plasticity. The CNS and the immune systems are known to be engaged in an
      intense bidirectional crosstalk, and glial cells are now viewed as a crucial
      third element of the synapse. In this opinion article, we review the principal
      mechanisms by which the immune system, and in particular immune diffusible
      mediators, influences synaptic transmission and the induction of brain plastic
      phenomena. Thereafter, we consider the potential implications of inflammation
      related overexpression of diffusible mediators in the disruption of synaptic
      plastic processes and neuronal networks functioning during human neurological
      diseases. Finally, we propose that a more accurate characterization of the
      mechanisms underlying the immune-mediated control of synaptic plasticity could
      represent, in the future, the basis for the development of a novel immune-centred
      therapeutic approach to neurological disorders.

PMID- 18617278
TI  - Prevention of cardiovascular events in early menopause: a possible role for
      hormone replacement therapy.
AB  - Heart disease is a major cause of illness and death in women. It is well known
      that there is an increase in cardiovascular disease and cardiovascular risk
      factors after the menopause, but it is still unclear whether the change in risk
      factors after the menopause is only related to the aging process or is
      principally due to estrogen deprivation. Observational studies suggest a
      protective role for estrogens, whereas recent randomized controlled trials report
      a negative effect of oral estrogens on primary and secondary prevention of
      cardiovascular events. The role of inflammation in the process of atherogenesis
      and in determining the cardiovascular disease risk in postmenopausal women has
      been focused only recently as well as the role of the estrogen receptor system in
      different tissues and the role of genetic susceptibility to adverse events during
      estrogen therapy. The objective of this work was to review the current
      understanding of the relationships between cardiovascular disease risk factors
      and hormonal age-related changes in postmenopausal women and particularly in
      early and surgical postmenopausal women, for a more appropriate evaluation of the
      expected effects of therapy with exogenous estrogens in a specific sample of the
      large population of postmenopausal women.

PMID- 18617279
TI  - Differential expression of cytokines, chemokines and chemokine receptors in
      patients with coronary artery disease.
AB  - Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of
      atherosclerosis through the production of inflammatory and anti-inflammatory
      cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8,
      CXCL9, CXCL10, IFN-gamma and IL-10 in vitro as well as the expression of the CCR2
      and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients
      with coronary artery disease (CAD) and healthy controls in the presence or
      absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive
      expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-gamma mRNA and, after
      stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control
      group. We also detected higher levels of CCL2 and CXCL8 in supernatants of oxLDL
      stimulated PBMCs from CAD patients than in corresponding supernatants from
      controls. Patients with CAD had a higher percentage of constitutive CCR2(+) and
      CXCR3(+) cells after stimulation with oxLDL. Among CAD patients, the main
      differences between the stable (SA) and unstable angina (UA) groups were lower IL
      10 mRNA production in the latter group. Altogether, our data suggest that PBMCs
      from CAD patients are able to produce higher concentrations of chemokines and
      cytokines involved in the regulation of monocyte and lymphocyte migration and
      retention in atherosclerotic lesions.

PMID- 18617280
TI  - Takotsubo cardiomyopathy as a potential cause of long QT syndrome and torsades de
      pointes.
AB  - Takotsubo cardiomyopathy is an increasingly reported syndrome characterized by
      transient apical left ventricular dysfunction in absence of flow limiting
      coronary artery disease. Prolongation of QT interval associated with Takotsubo
      cardiomyopathy has been previously reported in published case series but none of
      these series reported occurrence of torsades de pointes. Reported here is a case
      of Takotsubo cardiomyopathy resulting in QT prolongation and torsades de pointes
      in an emotionally distressed woman. The patient had a complete recovery of
      cardiac function in a week. Takotsubo cardiomyopathy should be considered among
      the causes of long QT syndrome and torsades de pointes.

PMID- 18617281
TI  - Incidence and outcome of femoral vascular complications among 18,165 patients
      undergoing cardiac catheterisation.
AB  - BACKGROUND: Arteriovenous fistulas (AVF) and arterial pseudoaneurysms (PSA) are
      potentially harmful complications of diagnostic and interventional cardiac
      catheterisation. Incidence, risk factors and clinical outcome are not well
      defined yet, although important for stratification and treatment. METHODS: A
      total of 18,165 consecutive patients undergoing cardiac catheterisation were
      enrolled in our prospective registry. For the diagnosis of AVF and PSA a clinical
      examination was performed in every patient followed by a Duplex examination in
      case of clinical suspicion of AVF/PSA. The impact of the following risk factors
      was assessed: age, body mass index, puncture of left vs. right groin, gender,
      hypertension, sheath size, peripheral artery disease, coumadin therapy,
      glycoprotein IIb/IIIa-inhibitors, pre-treatment with thrombolytics, and emergency
      procedures. RESULTS: Within 3 years a total of 334 complications were found
      (1.8%). The incidence of AVF and PSA was 0.6% (n = 107) and 1.2% (n = 227),
      respectively. The following significant independent risk factors were identified:
      arterial hypertension (odds ratio [OR]) = 1.86, female gender (OR = 1.65), and
      emergency procedures (OR = 2.13). During follow-up (mean 48 +/- 10 months) only
      11% of all AVF underwent operative repair due to symptoms. All PSA could be
      treated successfully either by manual compression, thrombin injection, or
      surgery. The overall mortality was 0.8%. CONCLUSION: Almost 2% of patients
      undergoing cardiac catheterisation acquire femoral AVF or PSA, for which patient-
      or procedure-related risk factors could be identified. Most of AVF and PSA could
      be managed conservatively or without any treatment, the overall mortality is low.

PMID- 18617283
TI  - Choice of contracts in the British National Health Service: an empirical study.
AB  - Following major reforms of the British National Health Service (NHS) in 1990, the
      roles of purchasing and providing health services were separated, with the
      relationship between purchasers and providers governed by contracts. Using a
      mixed multinomial logit analysis, we show how this policy shift led to a
      selection of contracts that is consistent with the predictions of a simple model,
      based on contract theory, in which the characteristics of the health services
      being purchased and of the contracting parties influence the choice of contract
      form. The paper thus provides evidence in support of the practical relevance of
      theory in understanding health care market reform.

PMID- 18617284
TI  - Comments to article: Henriksson R et al., Boron neutron capture therapy (BNCT)
      for glioblastoma multiforme: a phase II study evaluating a prolonged high-dose of
      boronophenylalanine (BPA) Radiother Oncol (2008).

PMID- 18617282
TI  - Morbidity and mortality among heart failure patients in Galicia, N.W. Spain: the
      GALICAP Study.
AB  - OBJECTIVE: Characterization of current morbidity and mortality among heart
      failure (HF) outpatients in Galicia (N.W. Spain), together with their main
      determinants. DESIGN: Prospective multicentre study involving 149 primary care
      physicians. SETTING: Primary care physicians selected randomly from among all
      (1959) primary care physicians in Galicia. PATIENTS: Clinical and epidemiological
      information for 1195 outpatients with HF were collected in 2006, with a mean
      follow-up of 6.5+/-1.5 months. MAIN OUTCOME MEASURES: Survival rates were
      calculated by Cox's proportional hazard model. RESULTS: Mean patient age was 76
      years, 48% were male, 82% had a history of arterial hypertension, and 32%
      ischaemic cardiopathy. Echocardiography had been performed in 67%, showing
      preserved systolic function in 61%. Ninety-two (8%) died during follow-up [74
      (80%) of them from cardiac causes], and 313 (29%) were re-admitted to hospital
      [230 (73%) of them for cardiac reasons]. Multivariate analysis identified the
      following independent predictors of cardiovascular death and/or readmission:
      ischaemic cardiopathy [hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.29
      4.40], stroke (HR 1.79, CI 1.18-2.73), oedema (HR 1.49, CI 1.10-2.03), anaemia
      (HR 1.66, CI 1.21-2.27), deteriorated systolic function (HR 1.62, CI 1.19-2.20),
      and previous cardiovascular admissions (HR 2.33, CI 1.67-3.24). Residence in the
      Barbanza district was identified as an independent predictor of survival free
      from cardiovascular admission (HR 0.56, CI 0.37-0.86). CONCLUSION: Morbidity and
      mortality are currently high among Galician HF patients, and their best single
      predictor is previous hospitalization for cardiovascular reasons.

PMID- 18617285
TI  - Quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef
      patties consumed by young children in French households.
AB  - A quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef
      patties consumed by children under 10 years of age in French households was
      conducted by a national study group describing an outbreak which occurred in
      France in 2005. Our exposure assessment model incorporates results from French
      surveys on consumption frequency of ground beef patties, serving size and
      consumption preference, microbial destruction experiments and microbial counts on
      patties sampled from the industrial batch which were responsible for the
      outbreak. Two different exposure models were proposed, respectively for children
      under the age of 5 and for children between 5 and 10 years. For each of these two
      age groups, a single-hit dose-response model was proposed to describe the
      probability of hemolytic and uremic syndrome (HUS) as a function of the ingested
      dose. For each group, the single parameter of this model was estimated by
      Bayesian inference, using the results of the exposure assessment and the
      epidemiological data collected during the outbreak. Results show that children
      under 5 years of age are roughly 5 times more susceptible to the pathogen than
      children over 5 years. Exposure and dose-response models were used in a scenario
      analysis in order to validate the use of the model and to propose appropriate
      guidelines in order to prevent new outbreaks. The impact of the cooking
      preference was evaluated, showing that only a well-done cooking notably reduces
      the HUS risk, without annulling it. For each age group, a relation between the
      mean individual HUS risk per serving and the contamination level in a ground beef
      batch was proposed, as a tool to help French risk managers.

PMID- 18617286
TI  - The metabolic syndrome identifies a heterogeneous group of metabolic component
      combinations in the Asia-Pacific region.
AB  - AIM: To compare the prevalence of metabolic syndrome (MetS) by combinations of
      MetS components derived from the National Cholesterol Education Program Adult
      Treatment Panel III (ATPIII) and International Diabetes Federation (IDF)
      definitions. METHODS: Four studies with ethnically distinct populations from the
      Asia-Pacific region were selected from the DETECT-2 study database. The
      prevalences of combinations of MetS components using the modified ATPIII
      (modATPIII) and IDF MetS definitions were compared between sexes and across
      populations. RESULTS: A total of 22,952 participants from Australia, Japan, Korea
      and Samoa were included. The age-adjusted prevalence of modATPIII MetS varied
      from 9.4 to 35.8% in men and 10.3 to 57.2% in women; results for IDF were
      generally higher. Prevalences of the 16 possible MetS component combinations from
      the modATPIII definition that result in a diagnosis of MetS ranged from 0 to
      12.7%. Of those with IDF-defined abdominal obesity, the prevalences of the 11 IDF
      defined MetS component combinations ranged from 0.2 to 18.3%. CONCLUSIONS: The
      large variation in the prevalence of possible MetS component combinations to
      diagnose MetS may explain the different risk of cardiovascular outcomes
      associated with MetS in different populations, especially since particular
      combinations of MetS components are associated with different risk of
      cardiovascular disease.

PMID- 18617287
TI  - The association of the PAX4 gene with type 1 diabetes in Han Chinese.
AB  - AIMS: In present study, we aimed to evaluate whether the paired box gene 4 (PAX4)
      may play a role in the pathogenesis of type 1 diabetes (T1D) in Chinese Han
      population. METHODS: One hundred and thirty-four cases with T1D and 324 non
      diabetic control subjects were selected randomly from Han Chinese. Three tag
      single nucleotide polymorphisms (SNPs, rs712701, rs2233580, rs2233575) according
      to HapMap data were selected to analyze. Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) was used to genotype. RESULTS: No
      difference was found in genotype or allele frequencies between patients and non
      diabetic controls in all three SNPs. No difference was found in common haplotypes
      constructed by these three SNPs, either. For the SNP rs2233575, in non-diabetic
      controls, the carriers with AA and GA genotypes had lower plasma insulin level
      than the subjects with GG genotype (P=0.048). CONCLUSIONS: The present study
      identified that the PAX4 gene was not associated with the risk of T1D in a Han
      Chinese sample, suggesting that it is unlikely to have a major effect on the
      susceptibility to T1D in this population. This is the first study on the PAX4
      gene in a Chinese population.

PMID- 18617289
TI  - Primary polymorphous low-grade adenocarcinoma of the bronchus: complete tumor
      removal with bronchoscopic resection.
AB  - Primary polymorphous low-grade adenocarcinoma (PLGA) is an uncommon malignant
      tumor arising from the minor salivary glands, but its occurrence as a primary
      tumor of the tracheobronchial tree is very rare. Herein, we have reported a rare
      case of endobronchial PLGA in a 56-year-old woman presenting with chronic cough
      and progressive exertional dyspnea. Chest CT clearly demonstrated an
      endobronchial tumor obstructing the distal part and bifurcation of the left main
      bronchus and causing distal atelectasis. She underwent rigid bronchoscope with
      electrocautery and bronchoscopic resection of the tumor. PLGA was diagnosed
      histologically. Subsequent left pneumonectomy was performed and showed no
      evidence of residual tumor.

PMID- 18617288
TI  - Morphogenetic competence of HNF4 alpha-deficient mouse hepatic cells.
AB  - BACKGROUND/AIMS: To specify roles of HNF 4 alpha in mouse liver development, we
      have analyzed the ex vivo morphogenetic potential of HNF4 alpha-null embryonic
      hepatic cells. METHODS: Using mice with floxed or deficiency alleles of HNF4
      alpha, hepatic cells lacking this transcription factor were explanted into
      primary culture and derived into cell lines. RESULTS: Contrary to behavior in
      vivo where HNF4 alpha-null liver cells fail to show normal polarity and
      epithelialization, e18.5 hepatic cells in primary culture from mutant embryos
      show restoration of apical expression of tight junction protein-1 and of
      transcripts for E-cadherin. Clones of control and HNF4 alpha-null cell lines were
      indistinguishable, even when differentiation of bile canalicular formation was
      induced. HNF4 alpha-null and control cell lines showed similar potential to
      colonize livers of the murine ALB-uPA/SCID model of liver regeneration, but null
      cells formed only bile ducts and not clusters of hepatocytes. Finally, analysis
      of mutant embryonic livers revealed a transcriptional signature consistent with a
      stress response, which could underlie the morphogenetic defects observed in vivo.
      CONCLUSIONS: We conclude that the lack of epithelialization characteristic of the
      HNF4 alpha-null embryonic liver is due, at least in part, to non-cell autonomous
      defects, and that null cells do not suffer intrinsic defects in polarization.

PMID- 18617290
TI  - The F658G substitution in Saccharomyces cerevisiae cohesin Irr1/Scc3 is semi
      dominant in the diploid and disturbs mitosis, meiosis and the cell cycle.
AB  - The sister chromatid cohesion complex of Saccharomyces cerevisiae includes
      chromosomal ATPases Smc1p and Smc3p, the kleisin Mcd1p/Scc1p, and Irr1p/Scc3p,
      the least studied component. We have created an irr1-1 mutation (F658G
      substitution) which is lethal in the haploid and semi-dominant in the
      heterozygous diploid irr1-1/IRR1. The mutated Irr1-1 protein is present in the
      nucleus, its level is similar to that of wild-type Irr1p/Scc3p and it is able to
      interact with chromosomes. The irr1-1/IRR1 diploid exhibits mitotic and meiotic
      chromosome segregation defects, irregularities in mitotic divisions and is
      severely affected in meiosis. These defects are gene-dosage dependent, and
      experiments with synchronous cultures suggest that they may result from the
      malfunctioning of the spindle assembly checkpoint. The partial structure of
      Irr1p/Scc3p was predicted and the F658G substitution was found to induce marked
      changes in the general shape of the predicted protein. Nevertheless, the mutant
      protein retains its ability to interact with Scc1p, another component of the
      cohesin complex, as shown by coimmunoprecipitation.

PMID- 18617291
TI  - Design, synthesis and antibacterial activity of novel actinonin derivatives
      containing benzimidazole heterocycles.
AB  - A series of novel actinonin derivatives containing a benzimidazole heterocycle
      linked as amide isostere have been designed and synthesized. The structures of
      all the synthesized compounds were confirmed by analytical and spectroscopic
      methods. All the compounds were evaluated in vitro against Staphylococcus aureus,
      Klebsiella pneumoniae, and Sarcina lutea. Among them, compound 1a with
      unsubstituted benzimidazole ring exhibited potent antibacterial activities.

PMID- 18617292
TI  - Oligonucleotide-polyamine conjugates: influence of length and position of 2'
      attached polyamines on duplex stability and antisense effect.
AB  - Tethering cationic ligands to oligonucleotides results in zwitterionic molecules
      with often improved target affinity and better cell membrane permeation. Due to
      the ideal distance between cationic groups, polyamines are perfect counter ions
      for oligonucleotides. Using an easy and versatile procedure for attaching ligands
      to the 2'-position, polyamines were conjugated to distinct terminal and internal
      positions of oligonucleotides. With polyamines attached to terminal nucleosides,
      the affinity to complementary DNA or RNA strands increased with growing number of
      cationic amines. Tethering polyamines to an internal nucleoside of wild type DNA
      oligonucleotides resulted in a considerable decrease in duplex stability, but in
      phosphorothioates, no significant decrease was detected. Conjugates exhibited
      progressively higher target downregulation ability with increasing polyamine
      chain length in a human melanoma cell culture assay.

PMID- 18617293
TI  - [Eosinophilic fasciitis and metastatic choroidal melanoma: a paraneoplastic
      syndrome?].
AB  - INTRODUCTION: Eosinophilic fasciitis (EF) is a rare inflammatory and fibrosing
      disorder with clinical, biological and histological characteristics. It has
      sometimes been reported with hematologic malignancy, but has never been
      associated with malignant uveal melanoma. CASE REPORT: A 67-year-old woman with
      choroidal melanoma was found to have metastatic skeletal extension of her
      melanoma while she developed swelling and pain in the lower limbs. Histologic
      examination confirmed an EF and oral corticosteroid treatment was started. A
      treatment for the ophthalmologic and skeletal extension of her melanoma was
      initiated. The paraneoplastic character of this EF was entertained. CONCLUSION:
      The simultaneous occurrence of EF and metastatic skeletal melanoma is suggestive
      of the possibility of EF constituting a paraneoplastic syndrome.

PMID- 18617294
TI  - Fighting rabies in Africa: the Africa Rabies Expert Bureau (AfroREB).
AB  - Rabies experts from 14 francophone African countries met in Grand Bassam (Cote
      d'Ivoire), 10-13 March 2008. They presented the situation in their respective
      countries, acknowledging the lack of rabies awareness among the population,
      health care workers and health authorities. They recognized that infrastructure
      for the management of rabies exposure is scarce, modern vaccines are in limited
      quantity and immunoglobulins are lacking in most of their countries. They defined
      as a priority the need to have reliable figures on the disease burden, which is
      necessary for informed decision making and priority setting, and for applying for
      aid in controlling the disease. This meeting sealed the establishment of the
      Africa Rabies Expert Bureau (AfroREB).

PMID- 18617295
TI  - Current issues in adolescent immunization.
AB  - Based on the December 2006 Fondation Merieux International Scientific Symposium,
      the current state of adolescent immunization is reviewed with a focus on the
      policy and programmatic issues that impact the acceptability, initiation, and
      successful implementation. Key questions are identified with proposed strategies
      to help achieve successful adolescent immunization programs. The role of current
      vaccines targeted to adolescents, such as those directed against invasive
      meningitis, pertussis, and the human papillomavirus, is reviewed as well as their
      role in rejuvenating interest in adolescent immunization, and more importantly,
      adolescent health as a whole.

PMID- 18617296
TI  - Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus
      influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae.
AB  - Conjugate vaccines exist that offer protection against disease caused by
      Haemophilus influenzae type b (Hib), and selected serogroups/serotypes of
      Neisseria meningitidis and Streptococcus pneumoniae. These vaccines are not only
      able to prevent serious disease, but they also provide protection against
      asymptomatic carriage. The resulting herd immunity effects have been striking,
      and have played an important role in the public health success of conjugate
      vaccination programmes. The aim of this paper is to review the state of the
      current evidence on conjugate vaccines and to identify important areas for
      further study, in order to inform the debate regarding the best use of these
      vaccines.

PMID- 18617297
TI  - Interesting and revealing CT.

PMID- 18617298
TI  - Post operative fluid balance in patients undergoing head and neck surgery.

PMID- 18617299
TI  - Management of Philadelphia negative chronic myeloproliferative disorders in
      pregnancy.
AB  - The management of pregnancy in Philadelphia negative chronic myeloproliferative
      disorders (CMPDs) is an increasingly frequent problem. In the literature, most
      pregnancies are reported for women with essential thrombocythemia (ET) with about
      400 pregnancies in about 200 women. In ET, first trimester abortion is the most
      frequent complication occurring in about one third of pregnancies. Interestingly,
      the incidence of maternal complications is relatively low with 3% for major
      thromboembolic and 2% for major bleeding events. The presence of the Jak2
      mutation seems to be an independent predictor of pregnancy complications.
      Pregnancies in ET should be stratified according to underlying risk factors in
      low, high and highest risk pregnancies. Women with low risk pregnancies are
      treated with low-dose aspirin, whereas women with high and higher risk
      pregnancies may benefit from low-dose aspirin plus interferon alpha +/- low
      molecular weight heparin throughout pregnancy and at least for six weeks post
      partum. In polycythemia vera (PV) there is only very few information on pregnancy
      outcome with 36 pregnancies reported in the literature. According to these data
      pregnancy in PV is per se a high risk situation. Accordingly, all women with PV
      should be treated with low-dose aspirin. Some pregnant PV patients may benefit
      from a more intensive therapy including interferon alpha +/- low molecular weight
      heparin throughout pregnancy and at least for six weeks post-partum.

PMID- 18617300
TI  - Determining metal origins and availability in fluvial deposits by analysis of
      geochemical baselines and solid-solution partitioning measurements and modelling.
AB  - Metals in floodplain soils and sediments (deposits) can originate from lithogenic
      and anthropogenic sources, and their availability for uptake in biota is
      hypothesized to depend on both origin and local sediment conditions. In criteria
      based environmental risk assessments, these issues are often neglected, implying
      local risks to be often over-estimated. Current problem definitions in river
      basin management tend to require a refined, site-specific focus, resulting in a
      need to address both aspects. This paper focuses on the determination of local
      environmental availabilities of metals in fluvial deposits by addressing both the
      origins of the metals and their partitioning over the solid and solution phases.
      The environmental availability of metals is assumed to be a key force influencing
      exposure levels in field soils and sediments. Anthropogenic enrichments of Cu, Zn
      and Pb in top layers could be distinguished from lithogenic background
      concentrations and described using an aluminium-proxy. Cd in top layers was
      attributed to anthropogenic enrichment almost fully. Anthropogenic enrichments
      for Cu and Zn appeared further to be also represented by cold 2M HNO3 extraction
      of site samples. For Pb the extractions over-estimated the enrichments. Metal
      partitioning was measured, and measurements were compared to predictions
      generated by an empirical regression model and by a mechanistic-kinetic model.
      The partitioning models predicted metal partitioning in floodplain deposits
      within about one order of magnitude, though a large inter-sample variability was
      found for Pb.

PMID- 18617301
TI  - Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: a
      12-month randomized trial.
AB  - BACKGROUND: Pentoxifylline potently inhibits cell proliferation, inflammation,
      and extracellular matrix accumulation. Human studies have proved its
      antiproteinuric effect in patients with glomerular diseases. Its benefit in
      addition to angiotensin receptor blockade in patients with chronic kidney disease
      is not clear. STUDY DESIGN: Randomized controlled study. SETTING & PARTICIPANTS:
      85 patients with estimated glomerular filtration rate (eGFR) of 10 to 60
      mL/min/1.73 m(2) and proteinuria with protein greater than 500 mg/g of creatinine
      on treatment with losartan, 100 mg/d, for longer than 6 months were screened in
      National Taiwan University Hospital. INTERVENTION: In the first stage (12
      months), group 1 served as control and group 2 was administered pentoxifylline.
      In the second stage (6 months), both groups were administered pentoxifylline. The
      pentoxifylline dose was 400 mg twice daily for patients with eGFR of 30 to 60
      mL/min/1.73 m(2) or once daily for patients with eGFR of 10 to 29 mL/min/1.73
      m(2). OUTCOMES: Proteinuria and eGFR. MEASUREMENTS: Proteinuria was assessed as
      total protein-creatinine ratio, eGFR was computed by using the Modification of
      Diet in Renal Disease Study equation. RESULTS: 27 and 29 patients were randomly
      assigned to groups 1 and 2, respectively. In the first stage, pentoxifylline
      decreased median proteinuria from 1,140 to 800 mg/g (median change, -23.9%)
      compared with 1,410 to 1,810 mg/g (median change, 13.8%) in the control group.
      The difference between groups was 38.7% (95% confidence interval, 25.7 to 51.6; P
      < 0.001). The change in proteinuria was related to the change in urinary tumor
      necrosis factor alpha and monocyte chemoattractant protein 1 excretion (R = 0.64
      and R = 0.55, respectively; P < 0.001 for both). In the second stage,
      pentoxifylline reproduced the change in proteinuria in group 1. LIMITATIONS:
      Small sample size, disease of late stages, open-labeled study. CONCLUSIONS:
      Pentoxifylline added to losartan therapy for 1 year decreased proteinuria in
      patients with CKD stages 3 to 5. A large-scale clinical trial is necessary to
      confirm this result.

PMID- 18617302
TI  - Variability of hepatitis B testing in British Columbian ESRD patients: the case
      to focus on implementation of guidelines.
AB  - BACKGROUND: Hepatitis B virus (HBV) immunization protocols are routinely followed
      in dialysis units. Recommendations for retesting and booster dose administration
      are variable and less well known. DESIGN: Quality improvement report. SETTING &
      PARTICIPANTS: Provincial dialysis cohort in all 5 regional centers in British
      Columbia (n = 1,055). QUALITY IMPROVEMENT PLAN: (1) Describe the variations in
      HBV testing practice patterns between centers and modalities of dialysis, (2)
      propose an evidence-based protocol for HBV follow-up testing, and (3) compare the
      current practice for HBV follow-up testing with the protocol. MEASURES: (1)
      Number of HBV tests performed based on geographic center and dialysis modality;
      (2) tabulation of local, national, and international guidelines to determine
      concordance and develop British Columbian protocol, and (3) percentage of
      patients who received recommended HBV testing based on protocol. RESULTS: (1)
      Significant variation noted in HBV testing frequency among the 5 regional centers
      and between hemodialysis and peritoneal dialysis patients (P < 0.001); (2)
      current available guidelines generally are concordant, but vary in regard to
      frequency of follow-up testing; and (3) comparing recommended testing frequency
      with actual testing, 50% of patients were tested as recommended; 13%, less than
      recommended; and 37%, more than recommended. Hemodialysis patients often were
      tested more than recommended (hemodialysis, 47% versus peritoneal dialysis, 16%;
      P < 0.01). Patients with current or past HBV infection were tested more than
      recommended (P < 0.01). All variability remained significant when adjusted for
      age, sex, and dialysis therapy duration in a multivariate model. LIMITATIONS: The
      cohort was ascertained from laboratory data; therefore, information for
      vaccination and booster dose administration was not available. CONCLUSION: In a
      cohort of dialysis patients initially screened for hepatitis B, 50% of patients
      are being appropriately monitored with retesting compared with an evidence-based
      protocol. Patients with known HBV infection and hemodialysis patients are being
      tested more than recommended. Adherence to a protocol for retesting would ensure
      appropriate follow-up and reduce unnecessary retesting, potentially leading to
      significant cost savings.

PMID- 18617303
TI  - Laparoscopic gastric banding surgery performed in obese dialysis patients prior
      to kidney transplantation.
AB  - Obese patients with end-stage renal disease who receive a kidney transplant
      experience greater rates of posttransplantation diabetes, delayed graft function,
      and local wound complications. Many centers exclude obese patients from
      transplantation programs. Diet, exercise, and medication in general are not
      reliable weight loss options for patients with end-stage renal disease; hence,
      bariatric surgery should be considered. We report 3 patients who underwent
      laparoscopically adjustable gastric banding, which enabled sufficient weight loss
      to gain eligibility for kidney transplantation. All these patients subsequently
      underwent successful uncomplicated kidney transplantations.

PMID- 18617304
TI  - The effect of on-line high-flux hemofiltration versus low-flux hemodialysis on
      mortality in chronic kidney failure: a small randomized controlled trial.
AB  - BACKGROUND: Given the paucity of prospective randomized controlled trials
      assessing comparative performances of different dialysis techniques, we compared
      on-line high-flux hemofiltration (HF) with ultrapure low-flux hemodialysis (HD),
      assessing survival and morbidity in patients with end-stage renal disease (ESRD).
      STUDY DESIGN: An investigator-driven, prospective, multicenter, 3-year-follow-up,
      centrally randomized study with no blinding and based on the intention-to-treat
      principle. SETTING & PARTICIPANTS: Prevalent patients with ESRD (age, 16 to 80
      years; vintage > 6 months) receiving renal replacement therapy at 20 Italian
      dialysis centers. INTERVENTIONS: Patients were centrally randomly assigned to HD
      (n = 32) or HF (n = 32). OUTCOMES & MEASUREMENTS: All-cause mortality,
      hospitalization rate for any cause, prevalence of dialysis hypotension, standard
      biochemical indexes, and nutritional status. Analyses were performed using the
      multivariate analysis of variance and Cox proportional hazard method. RESULTS:
      There was significant improvement in survival with HF compared with HD (78%, HF
      versus 57%, HD) at 3 years of follow-up after allowing for the effects of age (P
      = 0.05). End-of-treatment Kt/V was significantly higher with HD (1.42 +/- 0.06
      versus 1.07 +/- 0.06 with HF), whereas beta(2)-microglobulin levels remained
      constant in HD patients (33.90 +/- 2.94 mg/dL at baseline and 36.90 +/- 5.06
      mg/dL at 3 years), but decreased significantly in HF patients (30.02 +/- 3.54
      mg/dL at baseline versus 23.9 +/- 1.77 mg/dL; P < 0.05). The number of
      hospitalization events for each patient was not significantly different (2.36 +/-
      0.41 versus 1.94 +/- 0.33 events), whereas length of stay proved to be
      significantly shorter in HF patients compared with HD patients (P < 0.001). End
      of-treatment body mass index decreased in HD patients, but increased in HF
      patients. Throughout the study period, the difference in trends of intradialytic
      acute hypotension was statistically significant, with a clear decrease in HF (P =
      0.03). LIMITATIONS: This is a small preliminary intervention study with a high
      dropout rate and problematic generalizability. CONCLUSION: On-line HF may improve
      survival independent of Kt/V in patients with ESRD, with a significant decrease
      in plasma beta(2)-microglobulin levels and increased body mass index. A larger
      study is required to confirm these results.

PMID- 18617306
TI  - Association of Kt/V and creatinine clearance with outcomes in anuric peritoneal
      dialysis patients.
AB  - BACKGROUND: The 2006 Kidney Disease Outcomes Quality Initiative recommended a
      minimum total Kt/V of 1.7, eliminated creatinine clearance (Ccr) as a target, and
      recommended the use of ideal body weight to calculate Kt/V. We assessed these
      recommendations as predictors of outcomes in anuric peritoneal dialysis patients.
      STUDY DESIGN: Retrospective observational study using administrative data.
      SETTING & PARTICIPANTS: 1,432 peritoneal dialysis patients with anuria from
      January 1, 1994, to January 31, 2005, in a national sample (1,428 with Kt/V,
      1,416 with Ccr). PREDICTORS: Kt/V and Ccr at anuria; Kt/V based on actual body
      weight and ideal body weight. OUTCOMES & MEASUREMENTS: Association of dialysis
      adequacy with mortality and time to first hospitalization after anuria assessed
      by using accelerated failure time models. RESULTS: 293 anuric patients had Kt/V
      less than 1.7, 366 had Kt/V of 1.7 to 2.0, and 769 had Kt/V greater than 2.0,
      using actual body weight for calculation. In unadjusted analyses, Kt/V calculated
      using actual body weight both less than 1.7 (-41.3%; 95% confidence interval
      [CI], -55.5 to -22.6) and 1.7 to 2.0 (-26.1%; 95% CI, -42.6 to -4.6) were
      associated with shorter time to mortality. Kt/V calculated using actual body
      weight less than 1.7 was associated with shorter time to hospitalization (-38.1%;
      95% CI, -50.0 to -23.4), but Kt/V calculated using actual body weight of 1.7 to
      2.0 was not a significant predictor (-3.3%; 95% CI, -21.1 to 18.6). After
      adjustment, Kt/V calculated using actual body weight less than 1.7 remained
      associated with mortality (-25.3%; 95% CI, -41.1 to -4.8) and hospitalization (
      33.4%; 95% CI, -47.1 to -16.0). Ccr did not predict mortality. In unadjusted
      analysis, Ccr was not associated with hospitalization, but after adjustment, Ccr
      less than 50 L/wk/1.73 m(2) was significantly associated with shorter time to
      hospitalization (-19.9%; 95% CI, -35.0 to -1.3). Kt/V using ideal body weight was
      not a significant predictor in adjusted models. LIMITATIONS: This study was
      nonrandomized, with few malnourished patients. In addition, there is a potential
      for informative censoring for transfer to hemodialysis therapy before anuria.
      CONCLUSIONS: Kt/V calculated using actual body weight less than 1.7 in anuric
      peritoneal dialysis patients is associated with increased mortality and
      hospitalization. Use of ideal body weight to calculate Kt/V weakened the
      associations with outcomes and therefore cannot be recommended.

PMID- 18617307
TI  - Association of obstructive sleep apnea with urinary albumin excretion in
      essential hypertension: a cross-sectional study.
AB  - BACKGROUND: Microalbuminuria reflects a state of widespread vascular dysfunction,
      whereas obstructive sleep apnea (OSA) further promotes atherosclerotic damage in
      hypertension. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: In an
      outpatient hypertensive unit, 62 untreated hypertensive patients (aged 48 +/- 7
      years; office blood pressure [BP], 151 +/- 8/97 +/- 7 mm Hg) with OSA and 70
      hypertensive patients without OSA (apnea hypopnea index [AHI] < or = 5) matched
      for age, sex, smoking status, body mass index, and 24-hour pulse pressure were
      studied. PREDICTOR VARIABLE: Hypertension and OSA compared with hypertension
      without OSA. OSA defined as AHI greater than 5, documented by polysomnography.
      OUTCOME VARIABLE: Albuminuria assessed by urinary albumin-creatinine ratio (ACR).
      MEASUREMENTS: Participants underwent polysomnography, ambulatory BP monitoring,
      echocardiography, routine metabolic profile assessment, and glomerular filtration
      rate estimation, whereas ACR was measured from 2 nonconsecutive morning spot
      urine samples. RESULTS: Hypertensive patients with OSA compared with those
      without OSA showed increased 24-hour diastolic BP (87 +/- 7 versus 85 +/- 7 mm
      Hg; P = 0.03) and nighttime pulse pressure (50 +/- 10 versus 45 +/- 10 mm Hg; P =
      0.008), but did not differ regarding metabolic profile and estimated glomerular
      filtration rate. Albuminuria was greater by 57% in patients with OSA compared
      with those without OSA: log(10)ACR, 1.1 +/- 0.2 versus 0.7 +/- 0.4 mg/g; P <
      0.001). In the entire study population, log10(ACR) correlated with log10(AHI) (r
      = 0.35; P < 0.001), minimum oxygen saturation during sleep (r = -0.33; P <
      0.001), 24-hour pulse pressure (r = 0.38; P < 0.001), and nighttime pulse
      pressure (r = 0.21; P =0 .01). In a multivariable linear regression model,
      independent predictors of ACR were AHI (beta = 0.36; P < 0.001) and 24-hour pulse
      pressure (beta = 0.25; P = 0.01). LIMITATIONS: Cross-sectional study.
      CONCLUSIONS: Albuminuria increases within the normal range in hypertensive
      individuals with OSA compared with those without OSA proportionally to OSA
      severity independently of confounders. The association of upper-airway
      dysfunction with albuminuria and pulsatile hemodynamic load may provide an
      explanatory mechanism for the OSA-related risk in hypertension.

PMID- 18617305
TI  - Relations of measures of endothelial function and kidney disease: the Framingham
      Heart Study.
AB  - BACKGROUND: Endothelial dysfunction is prevalent in individuals with end-stage
      renal disease. Whether endothelial dysfunction is present in patients with
      moderate chronic kidney disease (CKD) is uncertain. STUDY DESIGN: Cross-sectional
      study. SETTINGS & PARTICIPANTS: Brachial reactivity measurements were obtained
      during the seventh examination cycle in 2,818 (diameter measurements) and 2,256
      (flow measurements) Framingham Heart Study Offspring cohort participants (53%
      women; mean age, 61 +/- 9 years). PREDICTOR: Estimated glomerular filtration rate
      less than 60 mL/min/1.73 m(2) derived from creatinine- and cystatin C-based
      estimating equations; microalbuminuria status. OUTCOME: Brachial reactivity
      measurements (baseline brachial diameter, flow-mediated dilation, baseline and
      hyperemic mean flow). MEASUREMENTS: Linear regression models were used to model
      brachial measures as a function of CKD and microalbuminuria status. RESULTS:
      Overall, 7.3% (n = 206) of participants had CKD, and of 2,301 with urinary
      measurements, 10.0% (n = 230) had microalbuminuria. Brachial reactivity measures
      did not differ significantly by CKD status in either creatinine- or cystatin C
      based equations in either age- and sex- or multivariable-adjusted models. In age-
      and sex-adjusted models, microalbuminuria was associated with decreased hyperemic
      mean flow (47.2 +/- 1.4 versus 51.4 +/- 0.5 mg/g; P = 0.005), but the association
      was not significant after multivariable adjustment (P = 0.09). LIMITATIONS:
      Predominantly white ambulatory cohort; results may not be generalizable to other
      ethnic groups or individuals with severe CKD. CONCLUSIONS: Endothelial
      dysfunction was not a major correlate of CKD in our sample.

PMID- 18617309
TI  - Toxmatch--a chemical classification and activity prediction tool based on
      similarity measures.
AB  - Chemical similarity forms the underlying basis for the development of
      (Quantitative) Structure-Activity Relationships ((Q)SARs), expert systems and
      chemical groupings. Recently a new software tool to facilitate chemical
      similarity calculations named Toxmatch was developed. Toxmatch encodes a number
      of similarity indices to help in the systematic development of chemical
      groupings, including endpoint specific groupings and read-across, and the
      comparison of model training and test sets. Two rule-based classification schemes
      were additionally implemented, namely: the Verhaar scheme for assigning mode of
      action for aquatic toxicants and the BfR rulebase for skin irritation and
      corrosion. In this study, a variety of different descriptor-based similarity
      indices were used to evaluate and compare the BfR training set with respect to
      its test set. The descriptors utilised in this comparison were the same as those
      used to derive the original BfR rules i.e. the descriptors selected were relevant
      for skin irritation/corrosion. The Euclidean distance index was found to be the
      most predictive of the indices in assessing the performance of the rules.

PMID- 18617310
TI  - Pediatric advanced life support re-training by videoconferencing compared to face
      to-face instruction: a planned non-inferiority trial.
AB  - STUDY AIM: Videoconferencing technology may be useful for providing Pediatric
      Advanced Life Support (PALS) re-training to geographically isolated providers.
      Yet, it is unclear whether learning outcomes will be similar to those obtained
      with traditional, face-to-face instruction. This study assess whether PALS re
      training provided via live, interactive videoconferencing was as effective as the
      same instruction provided in a face-to-face format on PALS knowledge, psychomotor
      skills, and confidence in performing resuscitation skills. METHODS: A planned non
      inferiority trial was used to test the hypothesis that outcomes of participants
      receiving instruction via videoconferencing would not be inferior to outcomes of
      participants receiving instruction in the traditional format at the conclusion of
      the course. In addition, knowledge and performance were reassessed at 1 year. A
      two-armed prospective design with participants randomly assigned to either a
      videoconferencing arm or a traditional arm was conducted. Non-inferiority was
      assessed through hypothesis testing and comparison of group differences to a non
      inferiority margin. RESULTS: No significant differences were detected among
      delivery methods for knowledge, psychomotor skill performance, or confidence at
      the conclusion of the course (all P's>0.10). Both groups showed a decline in
      knowledge and skill at 1 year; however, delivery methods did not differ (all
      P's>0.10). Differences among instruction methods did not exceed the non
      inferiority margin at the end of the course or at 1 year. CONCLUSIONS: For
      outcomes assessed following instruction and at 1 year, videoconferencing was not
      inferior to face-to-face delivery. These findings hold promise for use of
      videoconferencing to deliver PALS re-training to geographically isolated
      providers.

PMID- 18617308
TI  - Subjective and objective sleep quality in patients on conventional thrice-weekly
      hemodialysis: comparison with matched controls from the sleep heart health study.
AB  - BACKGROUND: Studies examining sleep in the hemodialysis (HD) population have
      largely lacked an adequate comparison group. It therefore is uncertain whether
      poor sleep quality in the HD population reflects age, chronic health conditions,
      or effects of conventional HD therapy. STUDY DESIGN: Cross-sectional matched
      group study. SETTING & PARTICIPANTS: Forty-six in-center HD patients were
      compared with 137 community participants participating in the Sleep Heart Health
      Study matched for age, sex, body mass index, and race. PREDICTOR: HD patients
      compared with community-dwelling non-HD participants. OUTCOMES & MEASUREMENTS:
      Home unattended polysomnography was performed and scored by using similar
      protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits
      Questionnaire and Epworth Sleepiness Scale. RESULTS: Average age of study samples
      was 63 years, 72% were white, and average body mass index was 28 +/- 5 kg/m(2).
      HD patients were significantly more likely than community participants to have
      short sleep (odds ratio, 3.27; 95% confidence interval, 1.16 to 9.25) and
      decreased sleep efficiency (odds ratio, 5.5; 95% confidence interval, 1.5 to
      19.6). HD patients reported more difficulty getting back to sleep (odds ratio,
      2.25; 95% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio,
      2.39; 95% confidence interval, 1.01 to 5.66). There was no association between
      polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or
      between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P =
      0.5) in the HD population. LIMITATIONS: The study was limited to participants
      older than 45 years. CONCLUSIONS: Kidney failure treated with thrice-weekly HD is
      significantly associated with poor subjective and objective sleep quality.

PMID- 18617312
TI  - A new emergency call system for rapid and accurate emergency medical service
      activation: the Ubiquitous Safe Call System.

PMID- 18617311
TI  - Serum concentration of NSE and S-100b during LVAD in non-resuscitated patients.
AB  - BACKGROUND AND OBJECTIVES: Increased serum concentrations of brain-derived
      proteins neuron-specific enolase (NSE) and protein S-100beta (S-100b) are used as
      early predictors of long-term outcome in unconscious survivors after
      cardiopulmonary resuscitation (CPR). We investigated whether use of short-term
      Left Ventricular Assist Devices (LVAD) in patients undergoing percutaneous
      coronary intervention (PCI) effect serum concentrations of NSE and S-100b,
      because use of such devices in resuscitated cardiogenic shock patients increased
      during the last years. METHOD: We analysed data from 80 consecutive non
      resuscitated patients who received LVAD support. 43 patients with uncomplicated
      myocardial infarction (AMI) without LVAD support after PCI formed the reference
      group. RESULTS: 69 patients (86%) with LVAD support survived and were discharged
      from hospital. We observed an increase in NSE serum levels in 93.6% and in S-100b
      serum levels in 58.6% of these patients during LVAD support. This increase was
      significant in comparison to the upper limit of normal (ULN) of both biomarkers
      and to the reference group. Cardiogenic shock patients showed significantly
      higher serum concentrations of both neuroproteins than patients after high-risk
      PCI, and after AMI during LVAD support. The use of axial flow pumps led to
      significantly higher serum concentrations of NSE compared to patients on IABP,
      but not of S-100b. Thrombocytes and haemoglobin (Hb) concentrations declined
      significantly during LVAD support. Surprisingly, we also observed a significant
      increase in NSE in the reference group. CONCLUSIONS: LVAD support after PCI is
      associated with a significant increase in NSE serum concentration as well as in S
      100b. We therefore postulate an overestimation of the extent of hypoxic brain
      damage in unconscious survivors after CPR if treatment include LVAD support or
      PCI or both procedures. The increase in NSE can be partly explained by alteration
      of thrombocytes and other blood cells. However, the increase in S-100b remains
      unexplained since S-100b does not occur in peripheral blood cells. An additional
      release of both biomarkers from ischemic myocardium or cerebral microembolism
      should be drawn into consideration.

PMID- 18617313
TI  - Impact of preexisting organ dysfunction on extracorporeal life support for non
      postcardiotomy cardiopulmonary failure.
AB  - BACKGROUND: Extracorporeal life support (ECLS) is associated with a high
      mortality rate in patients with preexisting multiple organ failure. To achieve
      better outcomes of ECLS in this high risk group, an understanding of the real
      impact of preexisting organ dysfunction on ECLS-associated mortality is
      necessary. METHODS: From January 2003 to March 2007, a total of 45 patients (mean
      age: 48 years) were placed on ECLS for acute cardiopulmonary failure and survived
      longer than 24h. The medical records of these 45 patients were retrospectively
      reviewed. The indications for ECLS were acute respiratory distress syndrome
      (n=23), acute myocarditis (n=10) and acute myocardial infarction (n=12). Organ
      failure was assessed based on the Sequential Organ Failure Assessment (SOFA)
      score, which was calculated daily until ECLS termination. The demographic
      variables, SOFA score variables, and ECLS-related complications, including renal
      dialysis, severe brain damage and limb ischemia, were analysed. RESULTS: Twenty
      seven patients (60%) were weaned from ECLS and 21 (47%) survived to discharge.
      Multivariate analysis revealed that the necessity of renal dialysis was an
      independent risk factor associated with failure to wean and non-survival, and the
      necessity of cardiopulmonary resuscitation (CPR) before ECLS was an independent
      risk factor for non-survival. Preexisting organ dysfunction, quantified by the
      pre-ECLS SOFA score, was predictive of survival to discharge. A pre-ECLS SOFA
      score greater than 14 predicted mortality in this study. CONCLUSIONS: SOFA score
      is a practical assessment tool and is predictive of ECLS-associated mortality in
      non-postcardiotomy patients. Patients having cardiac arrest requiring CPR or
      acute renal failure requiring dialysis before ECLS may have inferior ECLS
      outcomes.

PMID- 18617314
TI  - Chest compression quality and rescuer fatigue with increased compression to
      ventilation ratio during single rescuer pediatric CPR.
AB  - OBJECTIVE: The effects of the recommended 30:2 compression:ventilation (C:V)
      ratio on chest compression rate (CR), compression depth (CD), compression
      pressure (CP) and rescuer fatigue is unknown during pediatric CPR. We
      hypothesized that a 30:2 C:V ratio will decrease compression depth and
      compression pressure and increase rescuer fatigue compared with a 15:2 ratio.
      DESIGN: Randomized crossover observational study. METHODS: Adolescent, child and
      infant manikins were modified to digitally record compression rate, compression
      depth, compression pressure and total compression cycles (CC). BLS or PALS
      certified volunteers were randomized to five CPR groups: adolescent (AD), child 1
      hand (OH), child 2-hand (TH), infant two-finger (TF) and infant two-thumb (TT).
      Each rescuer performed each ratio for 5 min with the order randomized. Rescuer
      heart rate (HR) and respiratory rate (RR) were recorded continuously during CPR
      and used to determine the recovery time (RT) for HR/RR to return to baseline.
      Data (mean+/-S.D.) were contrasted by paired differences for quantitative data
      and the sign rank test for ordinal data. RESULTS: Eighty subjects (16 per group)
      were randomized. The peak compression pressure and compression rate were not
      different within any group, but total compression cycle were higher in all 30:2
      groups. Compression depth (mm) was not significantly different within any group.
      The rescuer's HR (bpm) increased significantly during 30:2 CPR in AD and OH group
      with no significant differences in RR and recovery time. Subjects reported that
      15:2 CPR was easier to perform (P<0.001). CONCLUSION: During single rescuer
      pediatric BLS, more compression cycles were achieved with 30:2 C:V ratio without
      effect on compression depth, pressure and rate. Increased HR with 30:2 C:V ratio
      was noted during larger manikin CPR without subjective difference of reported
      fatigue. Most rescuers in AD and TF group did not achieve recommended compression
      depth regardless of C:V ratio.

PMID- 18617315
TI  - The impact of prehospital transport interval on survival in out-of-hospital
      cardiac arrest: implications for regionalization of post-resuscitation care.
AB  - OBJECTIVE: There is growing evidence that therapeutic hypothermia and other post
      resuscitation care improves outcomes in out-of-hospital cardiac arrest (OHCA).
      Thus, transporting patients with return of spontaneous circulation (ROSC) to
      specialized facilities may increase survival rates. However, it is unknown
      whether prolonging transport to reach a designated facility would be detrimental.
      METHODS: Data from OHCA patients treated in EMS systems that cover approximately
      70% of Arizona's population were evaluated (October 2004-December 2006). We
      analyzed the association between transport interval (depart scene to ED arrival)
      and survival to hospital discharge in adult, non-traumatic OHCA patients and in
      the subgroup who achieved ROSC and remained comatose. RESULTS: 1846 OHCA occurred
      prior to EMS arrival. Complete transport interval data were available for 1177
      (63.8%) patients (study group). 253 patients (21.5%) achieved ROSC and remained
      comatose making them theoretically eligible for transport to specialized care.
      Overall, 70 patients (5.9%) survived and 43 (17.0%) comatose ROSC patients
      survived. Mean transport interval for the study group was 6.9 min (95% CI: 6.7,
      7.1). Logistic regression revealed factors that were independently associated
      with survival: witnessed arrest, bystander CPR, method of CPR, initial rhythm of
      ventricular fibrillation, and shorter EMS response time interval. There was no
      significant association between transport interval and outcome in either the
      overall study group (OR=1.2; 0.77, 1.8) or in the comatose, ROSC subgroup (OR
      0.94; 0.51, 1.8). CONCLUSION: Survival was not significantly impacted by
      transport interval. This suggests that a modest increase in transport interval
      from bypassing the closest hospital en route to specialized care is safe and
      warrants further investigation.

PMID- 18617316
TI  - Acute myocarditis secondary to Campylobacter jejuni enterocolitis.
AB  - Myocarditis is a rare condition that can mimic an acute coronary syndrome (ACS).
      We present the case of a 24-year-old male with Noonan syndrome who presented with
      a diarrhoeal pro-dromal illness, acute onset chest pain, elevated cardiac
      biomarkers and an abnormal ECG with ST elevation in the absence of obstructive
      coronary artery disease. The patient had acute myocarditis secondary to
      Campylobacter jejuni enterocolitis. Infective myocarditis is most commonly due to
      a viral infection. Myocarditis is very rarely due to a bacterial infection with
      only isolated reports of myocarditis induced by Campylobacter jejuni infection.
      At follow-up he remains well. Myocarditis should be considered in all patients
      presenting with acute onset chest pain and elevated cardiac biomarkers.

PMID- 18617317
TI  - Hyperkalemia induced failure of pacemaker capture and sensing.
AB  - Hyperkalemia may cause cardiac pacemaker (PMK) malfunctioning due to a reduction
      of the electronegativity of the resting myocardial potential. Both sensing and
      capture mechanisms could be temporarily affected, with possible life-threatening
      effects. Calcium chloride may counteract almost immediately such a dangerous
      effect of hyperkalemia, restoring the normal pacemaker function. We describe the
      case of a 75-year-old woman, observed in the Emergency Department for extreme
      weakness, very large QRS complexes, and a pacemaker type II exit block,
      associated with sensing failure and "spike-on-T" phenomenon. She was managed with
      immediate i.v. calcium chloride, followed by insulin/glucose and sodium
      bicarbonate infusions; the ECG recordings show an almost immediate correction of
      the PMK malfunctioning and serial improvement of the intraventricular conduction.
      This case supports the feasibility and effectiveness of i.v. calcium
      administration, as expected on the basis of electrophysiological ionized calcium
      effect on the threshold potential.

PMID- 18617318
TI  - Urogynecological training, testing and treatment among gynecologists in Germany.
AB  - OBJECTIVE: A survey was conducted to evaluate the urogynecology training of
      German gynecologists and the diagnostic tests and therapeutic options offered to
      women with incontinence or prolapse in hospital departments and private
      practices. STUDY DESIGN: Questionnaires were mailed to 3000 gynecologists in
      private practice and to 500 consultants in gynecology departments. The
      questionnaire included items on urogynecological training, diagnostic workup as
      well as conservative and surgical treatment options. RESULTS: The response rate
      was 16.8% with 589 of the 3500 questionnaires being returned. Less than one third
      of the respondents (28.6%) regard their training in urogynecology as good, 41%
      rate their training as moderate and 30.4% state that their urogynecology training
      during residency was inadequate. Male physicians significantly more often
      consider themselves well trained than women (p=.00006). The majority of
      gynecologists in private practice (74.7%) refer patients to a gynecological
      clinic for assessment of urogynecologic symptoms, 37.7% refer their patients to
      urologists in private practice, 10.4% to other gynecologists in private practice,
      and 10.4% to a urological clinic (percentages add up to more than 100% because
      multiple answers were allowed). Among the gynecologists who offer surgery, 81.2%
      perform retropubic TVT-operation and 80.1% colposuspension. Seventy-seven
      percentage of the gynecologists in private practice who do operations on an
      inpatient basis still perform anterior colporrhaphy to treat stress urinary
      incontinence compared to 62% of consultants in gynecological clinics (p<.05).
      CONCLUSION: One third of German gynecologists consider themselves inadequately
      trained in urogynecology. The results of our survey show that there is a need for
      improved general training during residency and for subspecialist training.

PMID- 18617319
TI  - Membrane fusion: a new function of non steroidal anti-inflammatory drugs.
AB  - Membrane fusion is an important event in many biological processes and is
      characterized by several intermediate steps of which content mixing between the
      two fusing vesicles signals the completion of the process. Fusion induced solely
      by small drug molecules is not a common event. Non Steroidal Anti-Inflammatory
      Drugs (NSAIDs), that control pain and inflammation, are also capable of
      exhibiting diverse functions. In this study we present a new function of NSAIDs
      belonging to the oxicam group, as membrane fusogenic agents. Small Unilamellar
      Vesicles (SUVs) formed by the phospholipid, dimyristoylphosphatidylcholine
      (DMPC), were used as model membranes. Fluorescence assays using
      terbium/dipicolinic acid (Tb/DPA) were used to monitor content mixing and
      corresponding leakage in presence of the drugs. Transmission Electron Microscope
      (TEM) was also used to image fusion bodies in drug treated vesicles as compared
      to the untreated ones. The results show that the three oxicam NSAIDs viz.
      Meloxicam, Piroxicam and Tenoxicam can induce fusion of DMPC vesicles and lead
      the fusion process to completion at a very low drug to lipid ratio (D/L) of
      0.045. The oxicam drugs exhibit differential fusogenic behavior as reflected in
      the kinetics of content mixing and leakage, both of which can be described by a
      single exponential rate equation. Moreover, not all NSAIDs can induce membrane
      fusion. Indomethacin, an acetic acid group NSAID and ibuprofen, a propionic acid
      group NSAID, did not induce fusion of vesicles. This new property of NSAIDs has
      important applications in biochemical processes.

PMID- 18617320
TI  - Sparganosis presenting as radiculalgia at the conus medullaris.
AB  - A 26-year-old female presented with severe lumbodorsal pain and hypesthesia in
      the right lower extremity. MRI of the spine revealed multiple lesions from L1 to
      S5; the largest was located at the conus medullaris. Diagnostic exploration
      revealed caseous, ivory-colored granulation tissue adhered to the conus
      medullaris and cauda eguina. Results of enzyme-linked immunosorbent assay and
      histopathological staining were consistent with sparganum infection. Our case
      report is unique because presentation was with lumbar radiculopathy instead of
      functional disorders of urination and defecation, atypical presentation for a
      conus medullaris lesion. Parasitic infection of the spinal cord with sparganosis
      should be considered when presentation is with signs and symptoms of spinal cord
      dysfunction of insidious onset.

PMID- 18617321
TI  - The option of Linac-based radiosurgery in a Gamma Knife radiosurgery center.
AB  - OBJECTIVE: Due to the fundamental differences in treatment delivery, linear
      accelerator-based radiosurgery can be complementary to Gamma Knife (GK) for
      intracranial lesions. We reviewed the effect of adding GK to an existing linear
      accelerator (Linac)-based radiosurgery practice and analyzed case selections for
      the two modalities. PATIENTS AND METHODS: UC Davis Medical Center installed a
      Leksell Gamma Knife Model C in October 2003 to supplement an established Linac
      based radiosurgery program. Radiosurgery indications for the 15 months before and
      after installation were compared. RESULTS: Radiosurgery cases expanded by twofold
      from 68 patients before GK installation to 139 after, with 106 treated by GK and
      33 by Linac. Besides a major increase for trigeminal neuralgia and a general
      growth for acoustic neuroma, meningioma and brain metastases, case numbers for
      glioma and arteriovenous malformation (AVM) remained stable. Considering case
      selections for Linac, glioma decreased from 28 to 18%, while meningioma and
      metastases increased from 9 to 21% and 38-46%, respectively. The Linac patients
      receiving fractionated treatment also increased from 37 to 61%. CONCLUSIONS:
      While the majority of patients were treated with GK, a significant proportion was
      judged to be suited for Linac treatment. This latter group included particularly
      patients who benefit from fractionated therapy.

PMID- 18617322
TI  - Mitochondria-cytochrome C-caspase-9 cascade mediates isorhamnetin-induced
      apoptosis.
AB  - Isorhamnetin is a flavanoid present in plants of the Polygonaceae family and is
      also an immediate metabolite of quercetin in mammals. Since the plasma level of
      isorhamnetin is maintained longer than quercetin, isorhamnetin may be a key
      metabolite to mediate the anti-tumor effect of quercetin. In the present study,
      we investigated the apoptotic mechanism of isorhamnetin in Lewis lung cancer
      (LLC) cells in vitro and established its in vivo anti-cancer efficacy. In cell
      culture, isorhamnetin significantly increased DNA fragmentation, and TUNEL
      positive apoptotic bodies and sub-G(1) apoptotic population in time- and dose
      dependent manners. Western blot analyses revealed increased cleavage of caspase
      3, and caspase-9 and PARP and increased cytosolic cytochrome C in isorhamnetin
      treated cells. These events were accompanied by a reduced mitochondrial
      potential. Apoptosis was blocked by a general caspase inhibitor or the specific
      inhibitor of caspase-3 or -9. These in vitro results support mitochondria
      dependent caspase activation to mediate isorhamnetin-induced apoptosis.
      Furthermore, an animal study revealed for the first time that isorhamnetin given
      by i.p. injection at a dose that is at least one order of magnitude lower than
      quercetin significantly suppressed the weights of tumors excised from LLC bearing
      mice. The in vivo anti-tumor efficacy was accompanied by increased TUNEL-positive
      and cleaved-caspase-3-positive tumor cells. Our data therefore support
      isorhamnetin as an active anti-cancer metabolite of quercetin in part through
      caspase-mediated apoptosis.

PMID- 18617323
TI  - Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide.
AB  - Buforin IIb is a novel cell-penetrating anticancer peptide derived from histone
      H2A. Here we analyzed the anticancer activity and cancer cell-killing mechanism
      of buforin IIb. Buforin IIb displayed selective cytotoxicity against 62 cancer
      cell lines by specifically targeting cancer cells through interaction with cell
      surface gangliosides. It traversed cancer cell membranes without damaging them
      and accumulated primarily in the nuclei. Once inside the cells, buforin IIb
      induced mitochondria-dependent apoptosis. In vivo analysis revealed that buforin
      IIb displayed significant tumor suppression activity in mice with tumor
      xenograft. Overall, these results suggest that buforin IIb constitutes a novel
      therapeutic agent for the treatment of cancers.

PMID- 18617324
TI  - Accidents involving liquids: a step ahead in modeling pool spreading, evaporation
      and burning.
AB  - The manuscript focuses on the modeling of industrial accidents involving liquid
      substances, i.e. liquid pools. The paper discusses how to improve Webber's model
      (1990) for evaluating the liquid pool dynamics in terms of spreading (onto land
      and water) and evaporation rates. In particular, our attention was devoted to the
      following points: friction term in presence of film boiling; evaluation of the
      friction velocity; determination of the wind profile index; evaluation of the
      conductive heat flux; the pool radius dynamics; turbulent mixing onto water;
      dispersion model input data. The paper presents, also, how to couple the proposed
      model to the pool burning dynamics. This allows simulating the burning of a
      spreading pool. Thanks to its prompt response in terms of CPU time, the proposed
      model is helpful not only under risk assessment or under emergency preparedness,
      but also during accident response. A comparison between experimental data and the
      model predictions validates the model effectiveness in simulating real accidental
      events.

PMID- 18617325
TI  - Simultaneous desulfurization and denitrification by microwave reactor with
      ammonium bicarbonate and zeolite.
AB  - Microwave reactor with ammonium bicarbonate (NH(4)HCO(3)) and zeolite was set up
      to study the simultaneous removal of sulfur dioxide (SO(2)) and nitrogen oxides
      (NO(x)) from flue gas. The results showed that the microwave reactor filled with
      NH(4)HCO(3) and zeolite could reduce SO(2) to sulfur with the best
      desulfurization efficiency of 99.1% and reduce NO(x) to nitrogen with the best
      NO(x) purifying efficiency of 86.5%. Microwave desulfurization and
      denitrification effect of the experiment using ammonium bicarbonate and zeolite
      together is much higher than that using ammonium bicarbonate or zeolite only.
      NO(x) concentration has little effect on denitrification but has no influence on
      desulfurization, SO(2) concentration has no effect on denitrification. The
      optimal microwave power and empty bed residence time (EBRT) on simultaneous
      desulfurization and dentrification are 211-280 W and 0.315 s, respectively. The
      mechanism for microwave reduced desulfurization and denitrification can be
      described as the microwave-induced catalytic reduction reaction between SO(2),
      NO(x) and ammonium bicarbonate with zeolite being the catalyst and microwave
      absorbent.

PMID- 18617326
TI  - The Fear Survey Schedule as a measure of anxious arousal: evidence from ERPs.
AB  - Anxious arousal and anxious apprehension have been proposed to be two aspects of
      anxiety that are differentially lateralized. Two prior event-related potential
      (ERP) studies have found right-lateralized ERPs that correlate with scores on the
      Fear Survey Schedule (FSS) but not with the Spielberger State-Trait Anxiety
      Inventory (STAI) scores. This study attempts to replicate the findings of right
      lateralization of FSS correlates using high-density ERPs (n=58). A spatial cueing
      task where emotional faces validly or invalidly cued targets was used. A right
      lateralized posterior component (P296) greatest in amplitude for high FSS scores
      was found. This finding further supports the proposition that the FSS measures
      anxious arousal and that anxious arousal can be right-lateralized.

PMID- 18617327
TI  - Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an
      experimental study.
AB  - Deficient endogenous pain inhibition, e.g. Diffuse noxious inhibitory controls
      (DNIC), or hormonal abnormalities like hypocortisolism, could be responsible for
      chronic widespread pain in Chronic Fatigue Syndrome (CFS). Thirty-one CFS
      patients with chronic pain and 31 healthy controls were subjected to spatial
      summation of thermal noxious stimuli by gradual immersion (ascending or
      descending) of the arm in warm water (46 degrees C). They rated pain intensity
      every 15s. Every immersion took 2 min, alternated with 5 min rest. Before and
      after immersion, salivary cortisol was assessed. Overall pain ratings were higher
      in CFS-patients, but the evolution was not different between patients and
      controls, during both ascending and descending immersion. Pain intensity and
      immersed surface were only correlated during the descending session in both
      patients (r=.334) and controls (r=.346). When comparing the first and the last
      15s of every emersion, it was found that pain inhibition starts slower for CFS
      patients in comparison to healthy subjects. Both pre- or post-values and cortisol
      response did not differ between controls and patients. The drop in cortisol was
      significantly correlated to pain intensity in CFS (r between .357 and .402). In
      addition to the hyperalgesia in CFS, DNIC react slower to spatial summation of
      thermal noxious stimuli. We found no evidence for hypocortisolism in CFS, and the
      cortisol response to nociception was not different in CFS compared to healthy
      subjects. In conclusion, delayed pain inhibition may play a role in chronic
      widespread pain in CFS but further research is required.

PMID- 18617329
TI  - AFM analysis of anisotropic dissolution in dense hydroxyapatite.
AB  - Dense, polycrystalline hydroxyapatite (HA) ceramics prepared by microwave
      sintering process were immersed for 1-60s in an acidic solution of pH 3, similar
      to the circumstance of osteoclastic resorption. Dissolution behavior on the
      surface of HA immersed in the solution was investigated. The surface topography
      was evaluated by using atomic force microscopy (AFM) with tapping mode. The
      erosion of grain boundaries in the dense HA was observed and the grain boundary
      dissolution occurred to a great extent forming a wide gap (50-100 nm) between
      grains. Notably, anisotropic dissolution was observed on the HA surface showing
      two topographically different regions; grains (Grain 1) with relatively intact
      surface, and grains (Grain 2) involving formation of subgrain boundaries and
      aligned crystallites in a certain direction. The difference in RMS surface
      roughness evidenced the distinct dissolution feature of ceramic grains. The
      surface roughness of Grain 1 increased from 1.45+/-0.30 to 3.11+/-0.63 nm,
      whereas the roughness of Grain 2 increased from 2.36+/-0.11 to 5.27+/-1.34 nm.

PMID- 18617330
TI  - Three-dimensional imaging in double aberration-corrected scanning confocal
      electron microscopy, part II: inelastic scattering.
AB  - The implementation of spherical aberration-corrected pre- and post-specimen
      lenses in the same instrument has facilitated the creation of sub-Angstrom
      electron probes and has made aberration-corrected scanning confocal electron
      microscopy (SCEM) possible. Further to the discussion of elastic SCEM imaging in
      our previous paper, we show that by performing a 3D raster scan through a
      crystalline sample using inelastic SCEM imaging it will be possible to determine
      the location of isolated impurity atoms embedded within a bulk matrix. In
      particular, the use of electron energy loss spectroscopy based on inner-shell
      ionization to uniquely identify these atoms is explored. Comparisons with
      scanning transmission electron microscopy (STEM) are made showing that SCEM will
      improve both the lateral and depth resolution relative to STEM. In particular,
      the expected poor resolution of STEM depth sectioning for extended objects is
      overcome in the SCEM geometry.

PMID- 18617331
TI  - Frequency of Giardia intestinalis assemblages isolated from dogs and humans in a
      community from Culiacan, Sinaloa, Mexico using beta-giardin restriction gene.
AB  - The assemblage of 37 Giardia intestinalis samples was determined, 19 obtained
      from puppy feces, 12 from stools of different human subjects under 3 years of age
      and 6 from axenic culture. The assemblages were classified according to the
      restriction pattern of beta-giardin gene with Hae III enzyme. Results showed that
      dog assemblages were grouped AI (52.6%) and AII (47.4%), while 41.7% human
      samples belonged to genotype AI and 58.3% to genotype AII. All axenic cultures
      belonged to assemblage AI; types AI and AII were both found in dog and human
      feces by Hae III restriction enzyme assay, suggesting a similarity between human
      and dog parasites. These results suggest that domestic animals infected with
      Giardia could produce cysts potentially infective for humans.

PMID- 18617332
TI  - A porcine model of full-thickness burn, excision and skin autografting.
AB  - Acute burn wounds often require early excision and adequate coverage to prevent
      further hypothermia, protein and fluid losses, and the risk of infection. Meshed
      autologous skin grafts are generally regarded as the standard treatment for
      extensive full-thickness burns. Graft take and rate of wound healing, however,
      depend on several endogenous factors. This paper describes a standardized
      reproducible porcine model of burn and skin grafting which can be used to study
      the effects of topical treatments on graft take and re-epithelialization.
      Procedures provide a protocol for successful porcine burn wound experiments with
      special focus on pre-operative care, anesthesia, burn allocation, excision and
      grafting, postoperative treatment, dressing application, and specimen collection.
      Selected outcome measurements include percent area of wound closure by
      planimetry, wound assessment using a clinical assessment scale, and histological
      scoring. The use of this standardized model provides burn researchers with a
      valuable tool for the comparison of different topical drug treatments and
      dressing materials in a setting that closely mimics clinical reality.

PMID- 18617333
TI  - Spinal nerve ligation-induced activation of nuclear factor kappaB is facilitated
      by prostaglandins in the affected spinal cord and is a critical step in the
      development of mechanical allodynia.
AB  - This study investigated the effect of 5th and 6th lumbar nerve (L5/L6) spinal
      nerve ligation (SNL) on activated nuclear factor kappaB (NFkBa) in nuclear
      extracts from the lumbar dorsal horn of the rat, and its relationship to
      prostaglandin (PG)-dependent spinal hyperexcitability and allodynia 3 days later.
      Male Sprague-Dawley rats, fitted with intrathecal (i.t.) catheters, underwent SNL
      or sham-surgery. Paw withdrawal threshold (PWT), electromyographic analysis of
      the biceps femoris flexor reflex, and immunoblotting of the spinal cord were
      used. Both allodynia (PWT <or=4 g) and exaggerated A- and C-fiber-mediated reflex
      responses (AFRR and CFRR), featuring decreased activation thresholds and evoked
      hyperexcitability, were evident only in nerve-ligated animals. This was preceded
      by an increase in NFkBa in the ipsilateral lumbar dorsal horn at 12 h which was
      still present 3 days after SNL. The amount of NFkBa in the ventral horns was
      unchanged compared with sham-controls. Blocking the activation of spinal
      NFkappaB, either directly with ammonium pyrrolidedithiocarbamate (PDTC; 100
      microg i.t.) or indirectly with S(+)-ibuprofen (100 microg i.t.) administered
      immediately after SNL, prevented the SNL-induced expression of spinal
      cyclooxygenase-2 and the development of spinal hyperexcitability and allodynia 3
      days later. R(-)-Ibuprofen and vehicle had no effect. These results demonstrate
      that NFkappaB is not only activated by SNL, but that spinal PG generated in the
      affected spinal cord from the onset of nerve injury facilitates this process.
      NFkappaB is a critical antecedent in the development of spinal PG-dependent
      hyperexcitability and allodynia in the SNL model.

PMID- 18617334
TI  - Loss of heterozygosity of the APC gene in oral squamous cell carcinoma.
AB  - The aim of this study was to investigate loss of heterozygosity (LOH) of the APC
      tumor suppressor gene loci, using restriction fragment length polymorphism
      polymerase chain reaction (RFLP-PCR) in 40 cases of oral squamous cell carcinoma
      (OSCC). Observed informativity was 72.5% for APC exon 11 and 82.5% for APC exon
      15. LOH at APC exon 11 was observed in 2 (6.9%) of 29 informative cases, and no
      LOH was observed for APC exon 15. Our results suggest that inactivation of the
      APC gene plays a minor role in the carcinogenesis of OSCC.

PMID- 18617335
TI  - Assessment of efficacy of a bivalent BTV-2 and BTV-4 inactivated vaccine by
      vaccination and challenge in cattle.
AB  - The efficacy of a bivalent inactivated vaccine against bluetongue virus (BTV)
      serotypes 2 (BTV-2) and 4 (BTV-4) was evaluated in cattle by general and local
      examination, serological follow-up, and challenge. Thirty-two 4-month-old calves
      were randomly allocated into 2 groups of 16 animals each. One group was
      vaccinated subcutaneously (s/c) with two injections of bivalent inactivated
      vaccine at a 28-day interval, and the second group was left unvaccinated and used
      as control. Sixty-five days after first vaccination, 8 vaccinated and 8
      unvaccinated calves were s/c challenged with 1 mL of 6.2 Log10 TCID50/mL of an
      Italian field isolate of BTV serotype 2, while the remaining 8 vaccinated and 8
      unvaccinated animals were challenged by 1 mL of 6.2 Log10 TCID50/mL of an Italian
      field isolate of BTV serotype 4. Three additional calves were included in the
      study and used as sentinels to confirm that no BTV was circulating locally. At
      the time of the challenge, only one vaccinated animal did not have neutralizing
      antibodies against BTV-4, while the remaining 15 showed titres of at least 1:10
      for either BTV-2 or BTV-4. However, the BTV-2 component of the inactivated
      vaccine elicited a stronger immune response in terms of both the number of virus
      neutralization (VN) positive animals and antibody titres. After challenge, no
      animal showed signs of disease. Similarly, none of the vaccinated animals
      developed detectable viraemia while bluetongue virus serotype 2 and 4 titres were
      detected in the circulating blood of all unvaccinated animals, commencing on day
      3 post-challenge and lasting 16 days. It is concluded that administration of the
      bivalent BTV-2 and BTV-4 inactivated vaccine resulted in a complete prevention of
      detectable viraemia in all calves when challenged with high doses of BTV-2 or BTV
      4.

PMID- 18617336
TI  - Identification of unreported putative new bovine papillomavirus types in
      Brazilian cattle herds.
AB  - The amplification by degenerate primers FAP59/FAP64 and sequencing allowed the
      detection of 15 putative new BPV types in cutaneous warts as well as in healthy
      skin. Four of these isolates were recently recognized as new BPV types (BPV-7, 
      8, -9, and -10) after determination of their complete genome sequences. In
      Brazil, investigations involving the definition of BPV types present in skin
      warts are still rare. The aim of the current study was to identify the BPV types
      associated with cutaneous papillomatosis observed in Brazilian cattle herds.
      Twenty-two cutaneous papilloma specimens were submitted to PCR assay employing
      the FAP primer pair. All PCR products with approximately 480 bp were submitted to
      direct sequencing. Cloning was performed for the amplicons which prior analysis
      revealed as putative new BPV types. From 16 cutaneous lesions, BPV-1, -2, and -6
      were identified in two, six, and eight papilloma specimens, respectively. In
      addition, four putative new BPV types were identified in other six skin warts,
      and then designated as BPV/BR-UEL2 to -5. The detection of the BPV-1, -2, and -6
      types in skin wart specimens supports the existence of these BPV types throughout
      the Brazilian cattle herd. In addition, the identification of four putative new
      BPV types is the first report of the presence of different BPV types in the
      American continent.

PMID- 18617337
TI  - Butyroyl-arginine as a potent virus inactivation agent.
AB  - Virus inactivation is a critical step in the manufacturing of recombinant
      therapeutic proteins, in particular antibodies, using mammalian expression
      systems. We have shown in the previous paper that arginine is effective in
      inactivation of herpes simplex virus type 1 (HSV-1) and influenza virus at low
      temperature under mildly acidic pH, i.e., above pH 4.0; above this pH,
      conformational changes of most antibodies are negligible. We have here extended
      virus inactivation study of arginine to other enveloped viruses, such as Sendai
      virus and Newcastle Disease Virus (NDV), and observed that arginine was
      ineffective against both viruses under the similar conditions, i.e., on ice and
      above pH 4.0. However, an arginine derivative, butyroyl-arginine, showed a strong
      virucidal potency against Sendai virus, leading to a 4log reduction in virus
      yield at pH 4.0, but not against NDV. In addition, although arginine and butyroyl
      arginine were equally effective against influenza virus having a cleaved form of
      hemagglutinin spike proteins, only butyroyl-arginine was significantly effective
      against the same virus, but having an uncleaved hemagglutinin spike proteins.
      Furthermore, butyroyl-arginine was more effective than arginine against HSV-1 at
      pH 4.5; i.e., it has a broader pH spectrum than does arginine.

PMID- 18617338
TI  - Influence of ageing, grinding and preheating on the thermal behaviour of alpha
      lactose monohydrate.
AB  - It is shown that the onset temperature and the magnitude of thermal events
      observed during DSC analyses of alpha-lactose monohydrate can be strongly
      affected by various treatments such as ageing, manual grinding and preheating
      (cycle of preliminary dehydration and rehydration). In the case of grinding and
      preheating, the change of dehydration pathways was further investigated by using
      a suitable combination of characterization techniques, including X-ray powder
      diffraction (XRPD) performed with a synchrotron source (allowing an accurate
      Rietveld analysis), scanning electron microscopy (SEM), laser particle size
      measurements, FTIR spectroscopy and (1)H NMR for the determination of beta
      lactose contents in samples. It appeared that the dehydration mechanism is
      affected not only by a smaller particle size distribution, but also by residual
      anisotropic lattice distortions and by the formation of surface defects or high
      energy surfaces. The fusion-recrystallization process occurring between anhydrous
      forms of alpha-lactose at ca. 170 degrees C is not significantly affected by
      grinding, whereas a preheating treatment induces an unexpected large increase of
      the enthalpy associated with this transition. Our observations and
      interpretations confirm the important role of water molecules in the crystal
      cohesion of the title compound and illustrate the necessity to consider the
      history of each sample for a satisfactory understanding of the physical
      properties and the behaviour of this important pharmaceutical excipient.

PMID- 18617339
TI  - Latent fingermark pore area reproducibility.
AB  - The study of the reproducibility of friction ridge pore detail in fingermarks is
      a measure of their usefulness in personal identification. Pore area in latent
      prints developed using cyanoacrylate and ninhydrin were examined and measured by
      photomicrography using appropriate software tools. The data were analysed
      statistically and the results showed that pore area is not reproducible in
      developed latent prints, using either of the development techniques. The results
      add further support to the lack of reliability of pore area in personal
      identification.

PMID- 18617340
TI  - Simultaneous squamous cell carcinoma with leiomyosarcoma of the larynx.
AB  - OBJECTIVE: To present the first reported case of a simultaneous squamous cell
      carcinoma with a leiomyosarcoma of the larynx, our treatment of the patient, and
      the 9-month follow-up results. STUDY DESIGN: Case study. METHODS: Review of
      diagnostic studies, the operative technique, and the patient's chart for the 9
      month period after treatment. RESULTS: A case with double laryngeal tumors with
      simultaneous evolution but different histological patterns is described. The
      squamous cell carcinoma and leiomyosarcoma involved both the vocal cords and the
      anterior commissure. A partial laryngectomy was performed, and the patient has
      been free of disease for 9 months. CONCLUSIONS: Multiple laryngeal tumors are
      exceedingly rare. To our knowledge, no previous reports of a simultaneous
      squamous cell carcinoma and a leiomyosarcoma of the larynx have been reported.
      Both tumors were not invasive in this case, so conservation surgery was feasible.

PMID- 18617341
TI  - Primary moderately differentiated neuroendocrine carcinoma (atypical carcinoid)
      of the larynx: A case report with immunohistochemical and molecular study.
AB  - Neuroendocrine tumours are the second most common laryngeal neoplasms, following
      squamous carcinoma. In this paper, we report the case of a moderately
      differentiated neuroendocrine carcinoma NEC (atypical carcinoid) of the larynx in
      a heavy smoker 67-year-old woman, with a history of hoarseness, dysphagia and
      dyspnea. The lesion was biopsied and microscopic examination revealed moderately
      differentiated NEC; thus the patient underwent supraglottic laryngectomy with
      lymphadenectomy. Here, we emphasized the morphological criteria for a correct
      pathological diagnosis. Moreover, because it has been demonstrated that many
      neuroendocrine neoplasms and malignant lesions of the larynx can be related to
      human papilloma virus (HPV), for the first time, we probed to verify if laryngeal
      neuroendocrine carcinoma could be due to an HPV infection by using polymerase
      chain reaction amplification (PCR) of tumoural DNA. On immunohistochemical
      analysis, the lesion characteristically revealed both neuroendocrine and
      epithelial differentiation with diffuse staining for chromogranin A,
      synaptophysin and neuron-specific enolase (NSE) and epithelial membrane antigen
      (EMA) and overexpression of p53 protein. PCR of NEC DNA did not show any signal
      for HPV DNA. Thus, this neoplasm is not due to an HPV infection, but a mutation
      of p53 gene which could cause immunohistochemical overexpression of p53 protein.

PMID- 18617342
TI  - Respiratory chain complex I deficiency in an infant with Ohtahara syndrome.
AB  - We report an infant with complex I deficiency of the mitochondrial respiratory
      chain whose most conspicuous symptom at presentation was an Ohtahara syndrome.
      Review of the literature suggest that association of these two conditions is
      extremely rare. Despite the few cases reported, in our view Ohtahara syndrome
      should be considered as one of the forms of presentation of mitochondrial
      dysfunction.

PMID- 18617343
TI  - MRI findings in renal transplant recipients with hip and knee pain.
AB  - PURPOSE: To evaluate and demonstrate the MRI findings of renal transplant
      recipients with hip and knee pain and to investigate the most common etiology of
      pain. MATERIALS AND METHODS: 69 hip MRIs of 57 patients with hip pain and 30 knee
      MRIs of 24 patients with knee pain with no history of trauma were retrospectively
      evaluated by two radiologists. RESULTS: In the evaluation of hip MRIs, 24
      patients had avascular necrosis and effusion, 2 patients had bone marrow edema
      consistent with early stage of avascular necrosis. 18 patients had only
      intraarticular effusion, 6 patients had tendinitis, 6 patients had bursitis and 1
      patient had soft tissue abscess. Five patients had muscle edema and five patients
      had muscle atrophy as additional findings to the primary pathologies. Among
      patients with knee pain, nine patients had degenerative joint disease. Seven
      patients had chondromalacia, five had bone marrow edema, six had meniscal tear,
      six had ligament rupture and two had bone infarct. Three of the patients had
      muscle edema accompanying to other pathologies. CONCLUSION: The most common
      etiology of hip pain in renal transplant recipients is avascular necrosis as
      expected, intraarticular effusion is found to be the second reason for pain.
      However, knee pain is explained by ligament pathology, meniscal tear,
      chondromalacia or degenerative joint disease rather than osteonecrosis.

PMID- 18617344
TI  - The mammography project at the SYRMEP beamline.
AB  - A clinical program for X-ray phase contrast (PhC) mammography with synchrotron
      radiation (SR) has been started in March 2006 at the SYRMEP beamline of Elettra,
      the SR facility in Trieste, Italy. The original beamline layout has been modified
      substantially and a clinical facility has been realized. In order to fulfill all
      security requirements, dedicated systems have been designed and implemented,
      following redundancy criteria and "fail safe" philosophy. Planar radiographic
      images are obtained by scanning simultaneously the patient and the detector
      through the stationary and laminar SR beam. In this first phase of the project a
      commercial screen-film system has been used as image receptor. Upon approval by
      the respective authorities, the mammography program is about half way to
      conclusion. Up to now about 50 patients have been examined. The patients are
      volunteers recruited by the radiologist after conventional examinations at the
      hospital resulted in an uncertain diagnosis. As an example one case of PhC SR
      mammography is shown and compared to conventional digital mammography.
      Preliminary analysis shows the high diagnostic quality of the PhC SR images that
      were acquired with equal or less delivered dose compared to the conventional
      ones.

PMID- 18617345
TI  - An initial clinical study on the efficacy of cisplatin-releasing gelatin
      microspheres for metastatic liver tumors.
AB  - PURPOSE: To evaluate the antitumor effect and side effects of cisplatin-releasing
      gelatin microspheres (Cis-GMSs) for metastatic liver tumors. METHODS: Cis-GMSs
      that degraded over 14 days were employed. The subjects comprised a total of nine
      cases. Transcatheter hepatic artery embolization (TAE) using Cis-GMSs (Cis-GMSs
      TAE) was performed 13 times in total. Six cases, each containing one to five
      tumors in a single segment to an entire lobe were treated by Cis-GMSs-TAE. In the
      remaining three cases with six or more metastatic liver tumors, the right and
      left lobes were treated by Cis-GMSs-TAE at a 2-week interval. RESULTS: There were
      two complete response (CR), one partial response (PR) and six stable disease (SD)
      cases. The response rate was 33.3%. The average rate of reduction in tumor
      diameter was 32%. Disappearance of metastatic liver tumors was observed in only
      two of the nine cases. As for side effects and complications, post-embolization
      syndrome was observed in eight cases, but no severe complications such as
      cholangitis or liver abscess were observed. CONCLUSION: Considering the mild side
      effects by Cis-GMSs-TAE, it is suggested that Cis-GMSs-TAE should be tried at
      least once as topical therapy for metastatic liver tumors when the response to
      systemic chemotherapy and other treatments is not satisfactory.

PMID- 18617346
TI  - Aeromonas tecta sp. nov., isolated from clinical and environmental sources.
AB  - Five Aeromonas strains, isolated from both clinical and environmental sources and
      characterized by a polyphasic approach, including phylogenetic analysis derived
      from gyrB, rpoD, and 16S rRNA gene sequencing, as well as DNA-DNA hybridization,
      extensive biochemical and antibiotic susceptibility tests, were recognized as
      members of an unknown, or undescribed, Aeromonas species. These "Aeromonas
      eucrenophila-like" strains were closely related to the species A. eucrenophila
      and Aeromonas encheleia, but they were negative for indole and acid from glycerol
      tests. Therefore, based on the results of the phylogenetic analyses and DNA-DNA
      pairing data of these strains, a novel species of the genus Aeromonas is
      described, for which the name Aeromonas tecta is proposed with isolate F518(T)
      (CECT7082(T), DSM17300(T), MDC91(T)) as the type strain.

PMID- 18617347
TI  - Dynamic magnetic resonance imaging of swallowing and laryngeal motion using
      parallel imaging at 3 T.
AB  - OBJECT: To evaluate the feasibility of an optimized MRI protocol based on high
      field imaging at 3 T in combination with accelerated data acquisition by parallel
      imaging for the analysis of oropharyngeal and laryngeal function. MATERIALS AND
      METHODS: Fast 2D gradient echo (GRE) MRI with different spatial resolutions
      (1.7x2.7 and 1.1x1.5 mm2) and image update rates (4 and 10 frames per second) was
      employed to assess pharyngeal movements and visualize swallowing via tracking of
      an oral contrast bolus (blueberry juice). In a study with 10 normal volunteers,
      image quality was semi-quantitatively graded by three independent observers with
      respect to the delineation of anatomical detail and depiction of oropharynx and
      larynx function. Additionally, the feasibility of the technique for the
      visualization of pathological pre- and post-surgical oropharynx and larynx
      function was evaluated in a patient with inspiratory stridor. RESULTS: Image
      grading demonstrated the feasibility of dynamic MRI for the assessment of normal
      oropharynx and larynx anatomy and function. Superior image quality (P<.05) was
      found for data acquisition with four frames per second and higher spatial
      resolution. In the patient, dynamic MRI detected pathological hypermobility of
      the epiglottis resulting in airway obstruction. Additional post-surgical MRI for
      one clinical case revealed morphological changes of the epiglottis and improved
      function, i.e., absence of airway obstruction and normal swallowing. CONCLUSION:
      Results of the volunteer study demonstrated the feasibility of dynamic MRI at 3 T
      for the visualization of the oropharynx and larynx function during breathing,
      movements of the tongue and swallowing. Future studies are necessary to evaluate
      its clinical value compared to existing modalities based on endoscopy or
      radiographic techniques.

PMID- 18617348
TI  - Determination of four polyphenolic active ingredients from a pharmaceutical
      preparation by capillary zone electrophoresis with amperometric detection.
AB  - The simultaneous determination of four active ingredients in Nao Xue Shuan
      Tablets, including ferulic acid, protocatechuic aldehyde, caffeic acid and
      protocatechuic acid was performed by capillary zone electrophoresis with
      amperometric detection (CZE-AD). The effects of working electrode potential, pH
      and concentration of running buffer, separation voltage and injection time on CZE
      AD were investigated. Under the optimum conditions, the four analytes could be
      perfectly separated within 18 min. A 300 microm diameter carbon-disc electrode
      had a good response at +0.95 V (vs. SCE) for the four analytes. The response was
      linear over three orders of magnitude with detection limits (S/N=3) as low as 10(
      8) or 10(-9) g/mL for the analytes. The assay results were satisfactory with
      recoveries in the range of 85.2-93.0% and RSDs less than 3.3%.

PMID- 18617349
TI  - HPLC-electrospray mass spectrometric assay for the determination of (R,R)
      fenoterol in rat plasma.
AB  - A fast and specific liquid chromatography-mass spectrometry method for the
      determination of (R,R)-fenoterol ((R,R)-Fen) in rat plasma has been developed and
      validated. (R,R)-Fen was extracted from 125 microl of plasma using solid phase
      extraction and analyzed on Atlantis HILIC Silica 3 microm column. The mobile
      phase was composed of acetonitrile:ammonium acetate (pH 4.1; 20mM) (85:15, v/v),
      at a flow rate of 0.2 ml/min. The lower limit of detection (LLOD) was 2 ng/ml .
      The procedure was validated and applied to the analysis of plasma samples from
      rats previously administered (R,R)-Fen in an intravenous bolus.

PMID- 18617350
TI  - Inductively coupled plasma mass spectrometry determination of metals in honeybee
      venom.
AB  - Inductively coupled plasma mass spectrometry (ICP-MS) technique was used to
      analyze the contamination of selected 20 metals in 32 samples of honeybee venom
      and to demonstrate differences in the content of these elements. Among the
      analyzed metal microelements (Al, Co, Cu, Zn, Mn, Mo, B, V, Sr and Ni), macro
      elements (Ca, Mg, K and Na) and toxic metals (As, Ba, Pb, Cd, Sb and Cr) were
      identified. The presented results showed that the metal levels in honeybee venom
      are much lower than the tolerable upper intake levels for the elements. Also the
      toxic metal contamination is much lower than the permissible levels for drugs
      established by the United States Pharmacopeia and the European Pharmacopeia. As
      opposed to the pharmacopeial tests for metals, a multi-element ICP-MS method has
      been developed. In order to confirm data obtained, the following steps and
      parameters were taken into account for the validation of the method: calibration
      verification, recovery, accuracy, precision, detection limit (LOD), quantitation
      limit (LOQ), spectral and matrix interference and comparison between ICP-MS and
      GFAAS (graphite furnace atomic absorption spectrometry) for Mn. All steps of
      validation proved the accuracy of the results. This is most likely the first
      study in which the metal content in honeybee venom was evaluated by ICP-MS.

PMID- 18617351
TI  - Investigation of mass-balance issue in e-beam sterilized paclitaxel eluting
      coronary stents by SPME/GC-MS.
AB  - Paclitaxel eluting coronary stents were sterilized by e-beam in a closed system,
      to investigate sterilization related mass-balance issues and evaluate potential
      volatile paclitaxel degradation products. A solid-phase microextraction (SPME)
      method utilizing a polydimethyl-siloxane/divinyl-benzene (PDMS/DVB) fiber was
      optimized for extracting the volatiles from the head-space of the sterilized
      stents. GC-MS was used for separation, identification, and quantitation of the
      components. Benzaldehyde and benzoic acid were identified as paclitaxel related
      volatile degradation products. Three groups of stents were included in the study,
      a control group (not exposed to e-beam), a group sterilized at 25 kGy, and a
      final group sterilized at 75 kGy. The stents sterilized by e-beam at 75 kGy
      contained significantly higher levels of benzoic acid relative to the controls
      and the stents at 25 kGy contained intermediate levels of benzoic acid. The
      benzaldehyde levels increased in the 25 kGy e-beam sterilized stents relative to
      the control but remained fairly constant in the 75 kGy e-beam sterilized stents
      relative to the 25 kGy e-beam results. Mechanism for the formation of benzoic
      acid and benzaldehyde from paclitaxel was proposed. The levels of benzoic acid
      and benzaldehyde observed on the stents did not resolve the original mass-balance
      issue, but most likely contribute to the lack of mass balance observed for
      paclitaxel.

PMID- 18617352
TI  - Immunoassays for the measurement of IGF-II, IGFBP-2 and -3, and ICTP as indirect
      biomarkers of recombinant human growth hormone misuse in sport. Values in
      selected population of athletes.
AB  - Insulin-like growth factor-II (IGF-II), insulin-like growth factor binding
      proteins (IGFBPs) -2 and -3 and C-terminal telopeptide of type I collagen (ICTP)
      have been proposed, among others, as indirect biomarkers of the recombinant human
      growth hormone misuse in sport. An extended intra- and inter-laboratory
      validation of commercially available immunoassays for biomarkers detection was
      performed. ELISA assays for total IGF-II, IGFBP-2 and IGFBP-3 (IGF-II/ELISA1:
      DSLabs, IGFBP-2/ELISA2: Biosource, and IGFBP-3/ELISA3: BioSource) and an EIA
      assay for ICTP (ICTP/EIA: Orion Diagnostica) were evaluated. The inter- and intra
      laboratory precision values were acceptable for all evaluated assays (maximum
      imprecision of 30% and 66% were found only for the lowest quality control samples
      of IGF-II and IGFBP-3). Correct accuracy was obtained for all inter-laboratory
      immunoassays and for IGFBP-2 intra-laboratory immunoassay. The range of
      concentrations found in serum samples under investigation was always covered by
      the calibration curves of the studied immunoassays. However, 11% and 15% of the
      samples felt below the estimated LOQ for IGF-II and ICTP, respectively, in the
      zone where lower precision was obtained. Although the majority of evaluated
      assays showed an overall reliability not always suitable for antidoping control
      analysis, relatively high concordances between laboratory results were obtained
      for all assays. Evaluated immunoassays were used to measure serum concentrations
      of IGF-II, IGFBP-2 and -3 and ICTP in elite athletes of various sport disciplines
      at different moments of the training season; in recreational athletes at baseline
      conditions and finally in sedentary individuals. Serum IGF-II was statistically
      higher both in recreational and elite athletes compared to sedentary individuals.
      Elite athletes showed lower IGFBP-2 and higher IGFBP-3 concentration with respect
      to recreational athletes and sedentary people. Among elite athletes, serum IGFBP
      3 (synchronized swimming), and ICTP (rhythmic gymnastics) concentrations were
      sport-dependent. Over the training season, within athlete variability was
      observed for IGFBP-2 in case of taekwondo and IGFBP-2 and -3 in case of
      weightlifting. Variations due to those aspects should be taken in careful
      consideration in the hypothesis of setting reference concentration ranges for
      doping detection.

PMID- 18617353
TI  - Childhood obesity prevention and treatment: recommendations for future research.
AB  - This report summarizes the National Heart, Lung, and Blood Institute Working
      Group's recommendations on future research directions in childhood obesity
      prevention and treatment. The Working Group consisted of leaders and
      representatives from public and private academic and medical institutions with
      expertise in a variety of health specialties. They reviewed the literature and
      discussed the findings as well as their own experiences in the prevention and
      treatment of childhood obesity. The Working Group made recommendations that were
      based on scientific importance, the potential likelihood of public health impact,
      and the feasibility and timeliness for childhood obesity prevention and treatment
      research. These recommendations are intended to assist investigators in the
      development of research agendas to advance the knowledge of effective childhood
      obesity prevention and treatment.

PMID- 18617354
TI  - The school food environment associations with adolescent soft drink and snack
      consumption.
AB  - BACKGROUND: Because students may purchase food and drinks in and around their
      schools, the school food environment may be important for obesity-related eating
      behaviors such as soft drink and snack consumption. However, research exploring
      the associations between school environments and specific eating behaviors is
      sparse. METHODS: Associations of the availability of canteen food and drinks, the
      presence of food stores around schools, and individual cognitions (attitudes,
      norms, modeling, perceived behavioral control, and intentions) with soft drink
      and snack consumption were examined in a cross-sectional study (2005-2006) among
      1,293 adolescents aged 12-15 years. Soft drink and snack consumption and related
      cognitions were assessed with self-administered questionnaires. The presence of
      food stores and the distance to the nearest food store were calculated within a
      500-meter buffer around each school. Data on the availability of soft drinks and
      snacks in school canteens were gathered by observation. In 2007, multilevel
      regression models were run to analyze associations and mediation pathways between
      cognitions, environmental factors, and behaviors. RESULTS: Adolescents'
      attitudes, subjective norms, parental and peer modeling, and intentions were
      positively associated with soft drink and snack consumption. There was an inverse
      association between the distance to the nearest store and the number of small
      food stores with soft drink consumption. These effects were mediated partly by
      cognitions. CONCLUSIONS: This study provided little evidence for associations of
      environmental factors in the school environment with soft drink and snack
      consumption. Individual cognitions appeared to be stronger correlates of intake
      than physical school-environmental factors. Longitudinal research is needed to
      confirm these findings.

PMID- 18617355
TI  - Trends in colorectal cancer screening disparities in people aged 50-64 years,
      2000-2005.
AB  - BACKGROUND: Colorectal cancer (CRC) screening rates are low, and racial, ethnic,
      and economic disparities have been reported. Whether disparities in CRC screening
      have decreased over time is unknown. This study aimed to determine whether
      progress was made between 2000 and 2005 in reducing CRC screening disparities by
      race, ethnicity, income, and insurance status. METHODS: Age-adjusted percentages
      of participants aged 50-64 who reported CRC screening (home fecal occult blood
      test in the past year or endoscopy in the past 10 years) were estimated from the
      2000 (n=6,020 participants) and 2005 (n=6,706) cancer control supplements of the
      National Health Interview Survey, with analysis in 2007. RESULTS: Screening rates
      did not increase between 2000 and 2005 for Hispanic women or uninsured women.
      Only for high-income participants did screening exceed 50%. For both men and
      women, the uninsured had the lowest levels of screening (19.1% and 19.3%,
      respectively, in 2005), and the greatest disparities were observed among groups
      defined by health insurance status. For women, disparities by ethnicity, income,
      and insurance status increased over time, whereas among men, disparities in 2005
      were similar to those in 2000. For Hispanic women, growing disparities were
      present at all income and insurance levels and persisted after additional
      adjustment. CONCLUSIONS: No progress was made in reducing most CRC screening
      disparities between 2000 and 2005. Methods are needed to increase CRC screening
      among everyone, but in particular Hispanic women and uninsured men and women.

PMID- 18617356
TI  - Risky driving among regular armed forces personnel from the United Kingdom.
AB  - BACKGROUND: Road traffic accidents are the leading cause of death for service
      personnel from the United Kingdom (UK). Little is known about the pattern of
      risky driving by these service personnel. METHODS: Cross-sectional data
      (collected postdeployment, between June 2004 and March 2006) were analyzed from a
      large, randomly selected cohort of military personnel from the UK. These analyses
      were limited to regular-service personnel who were drivers (n=8,127; 7,443 men
      and 684 women). "Risky driving" (not wearing a seatbelt, speeding, or both) was
      examined. Analyses were then repeated but restricted to those with experience of
      deployment to Iraq (n=4,611). All analyses were undertaken during 2007. RESULTS:
      Nineteen percent of armed forces personnel from the UK were defined as risky
      drivers. Risky driving was associated with being of young age; being male; being
      in the Army; childhood adversity; being deployed to Iraq; having a combat role;
      and being separated, divorced, or widowed. Restricting analyses to those deployed
      to Iraq revealed that risky driving was associated with increasing exposure to
      traumatic events and low in-theater morale. CONCLUSIONS: There are clear
      sociodemographic associations of risk-taking behaviors in the military
      population, and the study's results imply that risky driving is more common in
      drivers who had deployed.

PMID- 18617357
TI  - In vitro and in vivo inhibitory effect evaluation of cyclooxygenase-2 inhibitors,
      antisense cyclooxygenase-2 cDNA, and their combination on the growth of human
      bladder cancer cells.
AB  - Overexpression of cyclooxygenase (COX)-2 is associated with the progression of
      various malignancies, but the contribution of COX-2 expression, bioactivity or
      their cooperation to bladder cancer growth calls for further clarification. In
      this study, we investigated the inhibitory effect of COX-2 inhibitors, antisense
      COX-2 nucleotide, and their combination on the growth of bladder cancer cells
      (5637, 5637-P and 5637-AS). Suppression of either COX-2 expression or activity
      caused reduced cell proliferation, enhanced cell numbers in G(1) phase, and
      increased apoptosis; the joint suppression of COX-2 expression and bioactivity
      enhanced the degree of cell growth inhibition. COX-2 antisense-expressing 5637-AS
      tumors showed a 41.42+/-3.08% growth inhibition as compared with 5637 controls.
      Oral administration of indomethacin (3mg/kg) or celecoxib (15 mg/kg) caused tumor
      growth inhibition by 31.5+/-14.87% or 83.17+/-1.17%, respectively. When COX-2
      antisense cDNA and COX-2 inhibitor celecoxib were combined, the tumor growth
      inhibition rate was further increased up to 88.78+/-3.10%. These results provide
      evidence that celecoxib has potential therapeutic effect on bladder cancer, and
      the joint use of COX-2 antisense cDNA with celecoxib may improve their individual
      therapeutic effect, especially significantly increase the growth inhibitory
      effect of COX-2 antisense cDNA.

PMID- 18617358
TI  - Locked plating of supracondylar periprosthetic femur fractures.
AB  - Fifty periprosthetic supracondylar femur fractures above a total knee
      arthroplasty were reviewed. Fractures were closed Lewis and Rorabeck type II with
      a stable prosthesis. Twenty-nine patients (group I), were treated with locked
      condylar plating. Twenty-one patients (group II) were treated with nonlocked
      plating systems or intramedullary fixation. Minimum follow-up was 1.7 years.
      There were 5 malunions (20%) in group I and 9 (47%) in group II (P < .05). There
      were no nonunions in group I and 3 (16%) in group II. Complication rates were 12%
      in group I, compared to 42% in group II. Group I patients had less operative
      blood loss, healed in better alignment, and had greater knee motion. All 7
      patients treated with a retrograde intramedullary nail developed a malunion or
      nonunion. Locked plating is a reliable treatment for periprosthetic supracondylar
      femur fractures. We experienced a lower complication, revision, malunion, and
      nonunion rate with locked plating versus conventional treatment options.

PMID- 18617359
TI  - Cost-benefit comparison of the Oxford Knee score and the American Knee Society
      score in measuring outcome of total knee arthroplasty.
AB  - The American Knee Society score (AKSS) and the Oxford Knee score (OKS) are
      validated outcome measures for evaluation of total knee arthroplasties (TKAs). We
      investigated whether patient self-assessment using the OKS offers a viable
      alternative to clinical review using the AKSS. Preoperative, 2-year, 5-year, and
      10-year postoperative OKS and AKSS were reviewed from TKA patients. The scores
      were analyzed using the Pearson correlation. There was good correlation of OKS
      and AKSS at 2 years. This implies that patient self-assessment is a viable
      screening tool to identify which patients require clinical review, at 2 years,
      after TKA. However, the moderate correlation at 5 and 10 years indicates that
      clinical evaluation remains necessary at these time points.

PMID- 18617360
TI  - Initial results of managing severe bone loss in infected total joint arthroplasty
      using customized articulating spacers.
AB  - Twenty-three cases of infected total joint arthroplasty with substantial bone
      loss were treated with a cement spacer, which was customized intraoperatively to
      achieve joint stability and to allow motion. All but one of the patients were
      ambulatory with the spacer in place. Spacer dislocation occurred in 1 hip patient
      (9%) and in none of the knee patients. Articulating antibiotic-impregnated
      spacers with intraoperative customization is our preferred treatment of cases of
      infected total joint arthroplasty even in the presence of bone loss.

PMID- 18617361
TI  - Premixed antibiotic bone cement: an in vitro comparison of antimicrobial
      efficacy.
AB  - After Food and Drug Administration (FDA) approval of premixed antibiotic bone
      cements (polymethylmethacrylate [PMMA]), these products are being used with
      increasing frequency during revision and primary hip and knee arthroplasties. To
      date, no studies have compared the antimicrobial efficacy of more than 2 products
      directly. Using a 7-day modified Kirby-Bauer assay, we assessed the in vitro
      antibacterial properties of 5 FDA-approved, commercially available antibiotic
      PMMAs. Significant differences in antimicrobial activity were noted among the
      antibiotic PMMA products included in this investigation. Antibacterial activity
      of all products tested was greatest on day 1 and rapidly diminished thereafter.
      Results of this investigation suggest that the antibacterial efficacies of
      premixed antibiotic PMMA products are not equivalent.

PMID- 18617362
TI  - Angiosarcoma around a revision total hip arthroplasty and review of literature.
AB  - Development of cancer in association with metallic implants is well recognized
      yet poorly understood. We report a case of angiosarcoma at the site of a revision
      total hip arthroplasty. We found only 3 previous reports on angiosarcoma
      associated with hip arthroplasty in English literature. Association between
      malignant tumor and hip arthroplasty deserves attention because this surgical
      procedure is so common that possible risk of a neoplasm should be quantified.
      Sarcoma is rare, and its possible causation by retained foreign body material has
      been reported only as single cases.

PMID- 18617363
TI  - Intermediate results of simultaneous alumina-on-alumina bearing and alumina-on
      highly cross-linked polyethylene bearing total hip arthroplasties.
AB  - This study compared the clinical and radiographic results and the prevalence of
      osteolysis between alumina-on-alumina and alumina-on-highly cross-linked
      polyethylene bearings after cementless total hip arthroplasties in the 100
      patients younger than 50 years of age. There were 66 men and 34 women; the mean
      age at the time of surgery was 45.3 years (range, 25 to 49 years). The mean
      duration of follow-up was 5.6 years (range, five to seven years). The pre-and
      postoperative Harris hip scores were similar (39 and 41 points, respectively and
      93 points and 94 points, respectively). No acetabular or femoral component had
      aseptic loosening in either group. The mean annual penetration of the highly
      cross-linked polyethylene was 0.06 +/- 0.03 mm. No hip in either group had
      acetabular or femoral osteolysis.

PMID- 18617364
TI  - Computed tomography-based custom-made stem for dysplastic hips in Japanese
      patients.
AB  - We investigated 55 hips of 53 patients with dysplastic hips. Individual computed
      tomography data were used in the manufacturing of cementless custom-made stems
      made of Ti-6Al-4V. The proximal one third was coated using porous coating covered
      with hydroxyapatite coating. The average age at surgery was 60 years and the
      average follow-up was 7 years. Five patients (9%) complained of postoperative
      thigh pain. According to Engh's radiologic classification system, there was bone
      ingrown fixation in all hips. The cortical index and canal flare index were
      lower, and stem diameter was greater in the 11 hips (20%) with severe stress
      shielding than in the remaining 44 hips. Although the results obtained with this
      custom-made stem system for dysplastic hips were excellent, stress shielding is
      still an issue.

PMID- 18617365
TI  - Risk classification for primary knee arthroplasty.
AB  - We devised a 4-group classification for primary TKA patients: C0, fit patient,
      simple arthritis; CI, fit patient, complex arthritis; CII, medically unfit
      patient with simple pattern; and CIII, unfit patient with complex arthritis.
      Patient fitness and arthritis complexity were based on the literature. One
      hundred twenty-two patients, operated on by the senior author, were
      retrospectively placed into one of these 4 groups. We found the following:
      significantly increased cumulative complication risk in CII and CIII incomparison
      with C0 (P < .001), increased length of stay in CII and CIII (P < .001), and
      similar trends between C0 and CI and between CI and CII. This system is useful in
      preoperative planning, risk counseling, and surgeon selection. It identifies
      patients with a higher risk of complications and inpatient stay.

PMID- 18617366
TI  - Cytokine gene polymorphisms and fatigue in breast cancer survivors: early
      findings.
AB  - Converging evidence from basic and clinical studies suggests a role for
      proinflammatory cytokines in cancer-related fatigue, although the etiology of
      elevated inflammatory processes is unclear. We examined single nucleotide
      polymorphisms (SNPs) in the promoters of cytokine genes as genetic risk factors
      for cytokine-related fatigue in 33 fatigued and 14 non-fatigued breast cancer
      survivors, focusing on promoter sequence polymorphisms in IL1B and IL6 associated
      with differential expression of proinflammatory cytokines. Predictors of fatigue
      included presence of at least one cytosine at IL1B -511 (95%CI=0.91-16.6, p=.007)
      and homozygosity for either variant of the IL6 -174 genotype (G/G or C/C;
      95%CI=1.12-17.9, p=.027). Associations between fatigue status and IL1B genotype
      remained significant after covariate adjustment for demographic, biobehavioral
      and treatment-related factors. These findings provide preliminary evidence that
      polymorphisms in IL1B may serve as a potential risk factor for persistent fatigue
      in the aftermath of cancer.

PMID- 18617367
TI  - Deducing logical relationships between spatially registered cortical
      parcellations under conditions of uncertainty.
AB  - We propose a new technique, called Spatial Objective Relational Transformation
      (SORT), as an automated approach for derivation of logical relationships between
      cortical areas in different brain maps registered in the same Euclidean space.
      Recently, there have been large amounts of voxel-based three-dimensional
      structural and functional imaging data that provide us with coordinate-based
      information about the location of differently defined areas in the brain, whereas
      coordinate-independent, parcellation-based mapping is still commonly used in the
      majority of animal tracing and mapping studies. Because of the impact of voxel
      based imaging methods and the need to attribute their features to coordinate
      independent brain entities, this mapping becomes increasingly important. Our
      motivation here is not to make vague statements where more precise spatial
      statements would be better, but to find criteria for the identity (or other
      logical relationships) between areas that were delineated by different methods,
      in different individuals, or mapped to three-dimensional space using different
      deformation algorithms. The relevance of this problem becomes immediately obvious
      as one superimposes and compares different datasets in multimodal databases (e.g.
      CARET, http://brainmap.wustl.edu/caret), where voxel-based data are registered to
      surface nodes exploited by the procedure presented here. We describe the SORT
      algorithm and its implementation in the Java 2 programming language
      (http://java.sun.com/, which we make available for download. We give an example
      of practical use of our approach, and validate the SORT approach against a
      database of the coordinate-independent statements and inferences that have been
      deduced using alternative techniques.

PMID- 18617368
TI  - Diffusion-weighted imaging of primary brain lymphomas: effect of ADC value and
      signal intensity of T2-weighted imaging.
AB  - The purpose of this study was to determine whether apparent diffusion coefficient
      (ADC) value and T2 signal intensity (SI) in primary brain lymphomas affect their
      SI on diffusion-weighted images (DWI). On DWI of 16 brain lesions of 16 patients,
      9 (56.2%) were hyperintense (grade-3), 4 (25%) partially hyperintense (grade-2)
      and 3 (18.8%) isointense (grade-1). The mean ADC value of grade-3 lesions was
      significantly lower than of grade-1 lesions (p=0.028). The grade-1 lesions had
      ADC values of more than 0.8 and contrast-to-noise ratios of less than 18 on T2
      weighted images. Their ADC value and T2 signal intensity affect their SI on DWI.

PMID- 18617370
TI  - Verbal and visual memory: characterizing the clinical and intermediate phenotype
      in schizophrenia.
AB  - BACKGROUND: Verbal and visual memory deficits are prominent trait markers for
      schizophrenia, with impairments also observed in first-degree relatives [Snitz,
      B.E., Macdonald, A.W., 3rd, & Carter, C.S. (2006). Cognitive deficits in
      unaffected first-degree relatives of schizophrenia patients: a meta-analytic
      review of putative endophenotypes. Schizophr Bull, 32(1), 179-194]. It remains
      unclear whether deficits lie in encoding or savings, and whether the deficit is
      heritable. OBJECTIVE: To determine which features of memory performance are
      impaired in both patients and their healthy siblings, possibly reflecting shared
      genetic effects. METHOD: We tested episodic memory using Logical Memory (LM) and
      Visual Reproduction (VR) tasks of the Wechsler Memory Scale (Revised).
      Participants included patients with schizophrenia (n=162), their nonpsychotic
      siblings (n=146), and controls (n=205), recruited for the "CBDB/NIMH Sibling
      Study". We assessed immediate encoding and 30 minute and 24 hour delayed recall
      as well as savings scores for the "short delay" (immediate to 30 min) and "long
      delay" (30 min to 24 h) intervals. RESULTS: We observed marked verbal recall
      deficits in both patients and siblings compared to controls for all stages
      (p<.0001). Only patients experienced significant verbal and visual savings
      deficits over short delays (p<.0001) as well as verbal deficits over long delays
      (p<.005). In siblings, no saving score difficulty was apparent for either
      measure. CONCLUSIONS: Our results confirm shared impairment in verbal learning,
      but not memory, for both patients and siblings, therefore marking it as a
      potential schizophrenia-associated intermediate phenotype. The results implicate
      neural systems involved in immediate encoding and stabilization of memory
      representations in genetic risk for schizophrenia. In contrast, visual recall and
      savings impairments appear to be illness, i.e. state, deficits.

PMID- 18617371
TI  - Polymorphisms in human endogenous retrovirus K-18 and risk of type 2 diabetes in
      individuals with schizophrenia.
AB  - Type 2 diabetes is a major health problem in individuals with schizophrenia. The
      genetic basis of diabetes risk in individuals with schizophrenia has not been
      previously defined. We measured polymorphisms in a human endogenous retrovirus,
      Herv K-18, which is located in the CD48 signaling lymphocyte activating (SLAM)
      gene on chromosome 1. The study population consisted of 229 individuals with
      schizophrenia, 29 of whom had a history of type 2 diabetes, as well as 136
      control individuals without a history of a psychiatric disorder or type 2
      diabetes. We found that a haplotype defined by 2 polymorphisms in the envelope
      region of Herv K-18 is highly associated with type 2 diabetes in a population of
      229 individuals with schizophrenia, with an odds ratio of 9.0 (95% confidence
      limits 2.3-34.7, p<.001) adjusted for race, gender and type of antipsychotic
      medication. Lower levels of association were found in other polymorphisms located
      in the 3'untranslated region of Herv K-18 and in adjacent loci in CD48.
      Polymorphisms in endogenous retroviruses which are located near immunomodulatory
      genes may constitute risk factors for diabetes in individuals with schizophrenia.

PMID- 18617372
TI  - Outcome of patients with meticillin-resistant Staphylococcus aureus bacteraemia
      at an Emergency Department of a medical centre in Taiwan.
AB  - The number of patients presenting to the Emergency Department (ED) with
      meticillin-resistant Staphylococcus aureus (MRSA) is increasing, but few studies
      focus on patients with bacteraemia. From January 2001 to June 2006 the clinical
      characteristics and outcome of 177 consecutive patients with MRSA bacteraemia
      visiting an ED of a university hospital were studied. The average age of the
      patients was 65.8 years. Healthcare-associated MRSA bacteraemia comprised 76.3%
      of all cases. Catheter-related bacteraemia was the most common type of infection
      (22.6%), followed by soft tissue infection (20.9%) and primary bacteraemia
      (15.3%). Different types of infection were significantly related to different
      outcome. In-hospital mortality was 33.3%, but the mortality decreased to 17.7%
      when patients with rapidly fatal disease and mortality within 3 days were
      excluded. All isolates exhibited lower susceptibility to vancomycin (minimum
      inhibitory concentration (MIC) 1-2microg/mL). Factors associated with mortality
      included severity of underlying illness, severity of bacteraemia and persistent
      bacteraemia. A detrimental effect of elevated MIC could not be demonstrated
      despite applying several definitions of patient outcome. Patients admitted to the
      ED with MRSA bacteraemia carry high overall mortality; however, the severity of
      underlying illness, severity of bacteraemia and persistent bacteraemia are
      correlated with mortality, but not vancomycin MICs (2microg/mL) of MRSA isolates.

PMID- 18617369
TI  - Health and non-health care resources use in the management of adult outpatients
      with drug-resistant epilepsy in Spain: a cost-of-illness study (LINCE study).
AB  - PURPOSE: The purpose of this study was to ascertain health care and non-health
      care resources use in the past 12-months and to estimate the cost-of-illness in
      adult outpatients with drug-resistant epilepsy (DRE) in Spain. METHODS: A cross
      sectional and retrospective study was designed. Whole nation representative
      participants (epilepsy and general neurological clinics) were selected at random,
      but patients with drug-resistant epilepsy were included consecutively. We choose
      the societal perspective to compute total costs for this study. Estimation of
      costs was calculated by multiplying unitary costs by number of resources used.
      RESULTS: Seven hundred sixty-two consecutive patients (50.8% males) with mean
      (S.D.) age of 40.5 (13.5) years were included. Mean total yearly costs were
      euro6838 (euro8100) with health costs of euro4977 (euro6490), and indirect costs
      of euro1618 (euro4527). Gender and severity of seizures were significantly
      associated with costs; higher in males and subjects with severe seizures. Total
      annual costs showed a trend toward statistical significant association with age
      (lower costs in older patients), but costs were unrelated with level of care in
      Epilepsy or general neurological clinics. DISCUSSION: Health care, and to a
      lesser extend non-health care resources use, were high in patients with DRE in
      Spain, yielding a considerable burden to both the National Health System and the
      Society. Better planning of therapeutic strategies allowing alleviation of load
      and costs of this health problem should be considered from these findings.

PMID- 18617373
TI  - Prosthetic joint infections: microbiology, diagnosis, management and prevention.
AB  - Infections associated with prosthetic joints occur less frequently than aseptic
      failures but represent the most devastating complication, with high morbidity and
      substantial cost. The most important risk factors are co-morbidity and prior
      joint replacement (revision surgery). No single routinely used clinical or
      laboratory test has been shown to achieve ideal sensitivity, specificity and
      accuracy for the diagnosis of prosthetic joint infection (PJI). Therefore, only
      the sum of clinical signs and symptoms, blood tests, histopathology, radiography,
      bone scans and a microbiological work-up can provide an accurate diagnosis.
      Antimicrobial therapy must always be combined with the correct surgical
      treatment, which is chosen according to the duration of the infection and co
      morbidities of the patient. This review will briefly discuss the microbiology,
      diagnosis, management and prevention of PJI.

PMID- 18617374
TI  - Solid-state NMR studies of bacterial lipoteichoic acid adsorption on different
      surfaces.
AB  - Teichoic acids are important to bacteria for surface adhesion, metal ion
      coordination, and other biological processes crucial to bacterial survival. In
      particular, the surface adhesion of teichoic acids plays a crucial role in the
      formation of Gram-positive biofilms. Biofilms have been implicated as the major
      cause of various chronic infections. Biofilm formation is essentially a four-step
      process beginning with the adhesion of bacteria to a surface, followed by the
      excretion of an extracellular polymeric substance (slime), development and
      maturation of the biofilm architecture, and finally biofilm spreading through
      bacterial release. Currently, there is very little molecular level information
      available for the initial adhesion of bacteria to solid surfaces. Solid-state NMR
      is ideally suited for the study of these samples, thus we use (31)P solid-state
      NMR experiments to study the initial adhesion of lipoteichoic acid (LTA) to
      various surfaces. (31)P CP-MAS spectra and T(1)(rho) data demonstrate that the
      structure of LTA changes when adhered to cellulose, cell wall peptidoglycan
      (PGN), or TiO(2). However, when LTA is simultaneously adhered to PGN and TiO(2)
      the observed structure is dependent on the amount of retained water. For LTA on
      TiO(2), we suggest that the alanine and glucosamine groups interact with the
      surface. However, during simultaneous adhesion to TiO(2) and PGN, the glucosamine
      groups bind to the PGN while the alanine groups bind to the surface. This
      arrangement traps water between the PGN and TiO(2) surface.

PMID- 18617375
TI  - Directed aggregation and fusion of lipid vesicles induced by DNA-surfactants.
AB  - We investigated DNA-directed aggregation of vesicles using DNA-surfactants.
      Following tethering of single-stranded DNA oligonucleotides to vesicles using DNA
      surfactant, the tethered vesicles were assembled with other vesicles bearing
      complementary strands. The vesicle aggregation was strongly affected by the salt
      concentration and by temperature according to the characteristics of DNA
      hybridization. Restriction enzyme, which can hydrolyze the double-stranded DNA
      used in the present study, dissociated the vesicle aggregates. Exploration using
      fluorescently labeled vesicles suggested that the DNA-directed vesicle
      aggregation took place in a sequence-specific manner through DNA-duplex
      formation. Interestingly, the DNA-directed aggregation using short DNA-surfactant
      induced the fusion of vesicles to produce giant vesicles, resulting in an
      enzymatic reaction in the giant vesicle.

PMID- 18617376
TI  - Fragilidium duplocampanaeforme sp. nov. (Dinophyceae): a new phagotrophic
      dinoflagellate from the French Atlantic coast.
AB  - A new species of the genus Fragilidium, F. duplocampanaeforme sp. nov., is
      described from examinations by LM and SEM. This species has been recorded in
      summer on the French Atlantic coast, over a number of years. It was never
      abundant in the plankton and was very often associated with Fragilidium
      subglobosum, Pyrophacus horologium and also with toxigenic species of the genera
      Alexandrium and Dinophysis. Phagotrophy of F. duplocampanaeforme on Dinophysis
      prey is shown, and sexual reproduction is suggested by the observation of gamete
      like small forms. The size and the peculiar shape of its cells do not correspond
      to any known taxon, but the plate arrangement fits the genus Fragilidium. The
      plate formula is Po, Pc, 4', 8'', 10c, 6s?, 7''', 2"", 1p. A close examination of
      the plate morphology reveals an apical closing platelet Pc and significant
      differences from known Fragilidium species. Plate ornamentation is complex. A
      longitudinal fold and an unusual optional pore are seen on the antapical plate
      2"". Other distinctive morphological features are emphasized which discriminate
      this new species from others of the genus Fragilidium.

PMID- 18617377
TI  - Lipolytic effect of a polyphenolic citrus dry extract of red orange, grapefruit,
      orange (SINETROL) in human body fat adipocytes. Mechanism of action by inhibition
      of cAMP-phosphodiesterase (PDE).
AB  - The present study investigated the lipolytic (break of fat stored) effect of a
      citrus-based polyphenolic dietary supplement (SINETROL) at human adipocytes (ex
      vivo), body fat (clinical) and biochemical levels (inhibition of
      phosphodiesterase). Free fatty acids (FFA) release was used as indicator of human
      adipocyte lipolysis and SINETROL activity has been compared with known lipolytic
      products (isoproterenol, theopylline and caffeine). SINETROL stimulated
      significantly the lipolytic activity in a range of 6 fold greater than the
      control. Moreover, SINETROL has 2.1 greater activity than guarana 12% caffeine
      while its content in caffeine is 3 times lower. Clinically, two groups of 10
      volunteers with BMI relevant of overweight were compared during 4 and 12 weeks
      with 1.4 g/day SINETROL and placebo supplementation. In the SINETROL Group the
      body fat (%) decreased with a significant difference of 5.53% and 15.6% after 4
      and 12 weeks, respectively, while the body weight (kg) decreased with a
      significant difference of 2.2 and 5.2 kg after 4 and 12 weeks, respectively.
      These observed effects are linked to SINETROL polyphenolic composition and its
      resulting synergistic activity. SINETROL is a potent inhibitor of cAMP
      phosphodiesterase (PDE) (97%) compared to other purified compounds (cyanidin-3
      glycoside, narangin, caffeine). These results suggest that SINETROL has a strong
      lipolytic effect mediated by cAMP-PDE inhibition. SINETROL may serve to prevent
      obesity by decreasing BMI.

PMID- 18617378
TI  - Antimalarial, antimycobacterial and cytotoxic limonoids from Chisocheton
      siamensis.
AB  - Five limonoids isolated from the seeds of Chisocheton siamensis were tested for
      their antimalarial activity against Plasmodium falciparum, antimycobacterial
      activity against Mycobacterium tuberculosis and cytotoxic activity against NCI
      H187 (human small cell lung cancer), KB (oral human epidermal carcinoma) and MCF
      7 (breast cancer) cancer cell lines. All limonoids (1-5) showed inhibitory effect
      against Plasmodium falciparum with IC(50) values ranging from 2.06 to 6.31
      microg/ml. Only azadiradione (2) exhibited strong inhibitory effect against
      Mycobacterium tuberculosis with the MIC of 6.25 microg/ml. Compounds 1-4 also
      showed cytotoxic activity against NCI-H187, KB and MCF-7 cancer cell lines and
      dysobinine (1) had the highest activity with IC(50) of 1.67, 3.17 and 2.15
      microg/ml, respectively.

PMID- 18617379
TI  - Evaluation of disease-specific health-related quality of life in patients with
      pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) remains a debilitating and life
      threatening disease despite improvements in hemodynamics, exercise capacity and
      survival with recent therapeutic advances. Health-related quality of life (HRQOL)
      has, therefore, been proposed as an important outcome for evaluating care.
      Relatively little, however, is known regarding HRQOL or its determinants in PAH.
      The Minnesota Living with Heart Failure questionnaire was recently adapted and
      validated for HRQOL measurement in PAH. We applied this pulmonary hypertension
      specific version (MLHF-PH) to a larger population of PAH patients. METHODS:
      Ninety-three consecutive outpatients with PAH completed the MLHF-PH. Scores were
      assessed for correlations with demographics, symptoms, hemodynamics and
      treatments. RESULTS: Patients with PAH had significantly impaired HRQOL as
      assessed by the disease-specific MLHF-PH. Each physical and emotional component,
      as well as total scores on the MLHF-PH indicated severely depressed HRQOL. As
      compared to other diagnoses, PAH associated with scleroderma had the worst HRQOL.
      Patients with WHO functional Class II symptoms reported better HRQOL than Class
      III patients. Fatigue, weakness and abdominal discomfort were each associated
      with more severely depressed HRQOL, as was current epoprostenol use. With the
      sole exception of the right atrial pressure, hemodynamic measurements did not
      correlate with HRQOL scores. Simultaneous evaluation of HRQOL with a non-disease
      specific questionnaire (SF-36) revealed a similarly impaired status, although
      identified fewer associations with patient-specific factors. CONCLUSION: Severely
      impaired HRQOL is present in this population of patients with PAH evaluated with
      a disease-specific questionnaire. The availability of a pulmonary hypertension
      specific HRQOL questionnaire may enable further targeted investigations of
      factors that might improve outcomes.

PMID- 18617380
TI  - Using laboratory measurements to predict in-flight desaturation in respiratory
      patients: are current guidelines appropriate?
AB  - In an attempt to guide physicians asked by respiratory patients for advice on
      flight fitness, the British Thoracic Society (BTS) have published guidelines on
      fitness to fly. The main potential hazard is hypobaric hypoxia, and efforts have
      focused on the prediction of hypoxia in individuals. The present study examines
      10 years' experience of hypoxic challenge (HC) of respiratory patients to
      evaluate if the guidelines recommended by the BTS are appropriate. One hundred
      and eighteen patients (67 female, mean age 65.6+/-11.4 (SD) years) were referred
      for assessment. Patients underwent HC using a 40% Venturi mask supplied with 100%
      N(2) which lowered the F(i)O(2) to 15.1%. A further 13 patients on long-term
      oxygen therapy also underwent HC whilst receiving supplemental oxygen. In
      agreement with the BTS guidelines, all patients with a sea level SpO(2) of over
      95% maintained their SpO(2) > or = 90% during HC. One third of patients with sea
      level SpO(2) of 92-95%, but no other risk factor (as defined by the guidelines)
      also desaturated below 90% during HC. Thirty-two patients were assessed as fit to
      fly with supplemental oxygen. Our results support the BTS guidelines for patients
      with a sea level SpO(2) > 95% but suggest that some revision is required for
      patients with a sea level SpO(2) of 92-95%. It was not possible to predict from
      either initial SpO(2) or spirometry which individuals were at risk of
      desaturation below 90% during hypoxic challenge.

PMID- 18617381
TI  - Aging and induced senescence as factors in the pathogenesis of lung emphysema.
AB  - Classically, the development of emphysema in chronic obstructive pulmonary
      disease is believed to involve inflammation induced by cigarette smoke and
      leukocyte activation, including oxidant-antioxidant and protease-antiprotease
      imbalances. While there is substantial evidence for this, additional aspects have
      been suggested by a number of clinical and experimental observations. Smokers
      exhibit signs of premature aging, particularly obvious in the skin. The link
      between aging and chronic disease is well-known, e.g., for the brain and
      musculoskeletal or cardiovascular system, as well as the clinical link between
      malnutrition and emphysema, and the experimental link to caloric restriction.
      Interestingly, this intervention also increases lifespan, in parallel with
      alterations in metabolism, oxidant burden and endocrine signaling. Of special
      interest is the observation that, even in the absence of an inflammatory
      environment, lung fibroblasts from patients with emphysema show persistent
      alterations, possibly based on epigenetic mechanisms. The importance of these
      mechanisms for cellular reprogramming and response patterns, individual risk
      profile and therapeutic options is becoming increasingly recognized. The same
      applies to cellular senescence. Recent findings from patients and experimental
      models open novel views into the arena of gene-environment interactions,
      including the role of systemic alterations, cellular stress, telomeres, CDK
      inhibitors such as p16, p21, pRb, PI3K, mTOR, FOXO transcription factors, histone
      modifications, and sirtuins. This article aims to outline this emerging picture
      and to stimulate the identification of challenging questions. Such insights also
      bear implications for the long-term course of the disease in relation to existing
      or future therapies and the exploration of potential lung regeneration.

PMID- 18617382
TI  - Why does gender influence survival in obstructive sleep apnoea?
AB  - The study aim was to compare the mortality risk of men and women diagnosed with
      obstructive sleep apnoea (OSA) and started on treatment with continuous positive
      airway pressure (CPAP). From August to December 2003 we reviewed the hospital
      records of patients who had started on CPAP for OSA between July 1995 and June
      1998. Mortality rates were compared between men and women. Associations with
      mortality risk were determined using univariate and multivariate Cox's
      proportional hazards regression. The sample comprised 292 men and 47 women. Eight
      percent of the men and 23% of the women died (p=0.003). Univariate analysis
      showed increased mortality risk was associated with female sex, greater age when
      CPAP was started, a pre-treatment minimum nocturnal oxygen saturation (SpO(2))
      <75%, a higher Charlson comorbidity index score and discontinuation of CPAP
      treatment. Female sex remained associated with increased mortality independent of
      age, minimum SpO(2) and CPAP use, but was not independent of the Charlson score.
      Women diagnosed with OSA and treated with CPAP demonstrated a 3.44 greater
      mortality risk than men, mostly due to greater comorbidity.

PMID- 18617383
TI  - Physiology of the small airways: A gender difference?
AB  - Small airways are affected in asthma, but gender differences have not been
      investigated. This study aims to assess whether gender differences exist in the
      extent of small airway involvement in asthma. Sixteen patients with mild-to
      moderate asthma (seven males, median (range) age 39 (19-56) years,
      FEV(1)%predicted 89% (62-120), PC(20) Methacholine (MCh) 0.4 mg/mL (0.1-4.2))
      participated in the study. MCh-induced air trapping at end-expiratory CT scans,
      alveolar and bronchial exhaled Nitric Oxide (eNO), Single-Breath N(2) closing
      volume, FEF(25-75%), FEF(50%) and % change in FVC at PC(20) adenosine-5'
      monophosphate (AMP) and at PC(20)MCh were evaluated. Multiple regression analyses
      evaluated whether gender, body mass index and age were explanatory variables for
      the severity of air trapping. Males had significantly larger MCh-induced
      increases in low attenuation areas on CT than females, 6% (1-9) versus 2% (-1-7),
      p=0.012. Males had significantly more signs of MCh-induced air trapping in the
      non-dependent lung lobes than females. Male gender was the sole factor explaining
      higher values of MCh-induced signs of air trapping. Females had higher bronchial
      eNO values than males, 4 nL/s (2-7) versus 2 nL/s (1-4), p=0.04. Small airway
      involvement in asthma as reflected by MCh-induced air trapping at CT was
      significantly larger in males than females even in this relatively small group.
      Bronchial eNO, reflecting partially small airway inflammation, was higher in
      females than males. These data suggest that the small airways are affected
      differently in males and females with asthma. Males exhibit small airway
      involvement by attenuated small airway patency and females by small airway
      inflammation.

PMID- 18617384
TI  - Direct and rapid electrochemical biosensing of the human interleukin-2 DNA in
      unpurified polymerase chain reaction (PCR)-amplified real samples.
AB  - Electrochemical detection of polymerase chain reaction (PCR)-amplified human
      interleukin-2 (IL-2) coding DNA sample (399bp size) without any purification and
      pre-treatment is described. To achieve this goal, a sensor was made by
      immobilization of a 20-mer oligonucleotide (chIL-2) as the probe on the pencil
      graphite electrode (PGE). This probe is related to the antisense strand of human
      interleukin-2 gene. The results showed that the electrode could effectively sense
      the PCR product of human interleukin-2 DNA by anodic differential pulse
      voltammetry (ADPV) based on guanine oxidation signal. In order to inhibit PCR
      components interfering effects and improve biosensing performance, various
      factors were investigated. We found that the desorption of non-specifically
      adsorbed components of the unpurified PCR samples from PGE surface is easily
      achieved by washing of the electrode in washing solution for about 300s. The
      effectiveness of this procedure was confirmed using purified PCR samples. The
      selectivity of the sensor was assessed with negative control PCR sample and seven
      different non-complementary PCR products corresponding to 16S rDNA (bigger than
      1500bp) of various bacterial genuses. Diagnostic performance of the biosensor is
      described and the detection limit is found to be 69pM. The reliability of the
      electrochemical biosensing results was verified by electrophoresis of the PCR
      products.

PMID- 18617385
TI  - Low-dose ropivacaine-sufentanil spinal anaesthesia for  caesarean delivery: a
      randomised trial.
AB  - BACKGROUND: It is well known that intrathecal opioids have a synergic effect with
      spinal local anaesthetics. The aim of this study was to evaluate whether low-dose
      ropivacaine in combination with sufentanil could produce effective spinal
      anaesthesia with less maternal hypotension and vomiting than ropivacaine alone.
      METHODS: 80 ASA I and II parturients undergoing elective caesarean delivery under
      combined spinal-epidural anaesthesia were randomly allocated to two groups. Group
      R15 received intrathecal hyperbaric ropivacaine 15 mg and group SR10 hyperbaric
      ropivacaine 10 mg with sufentanil 5 micrograms. Characteristics, efficacy and
      side effects of spinal anaesthesia in each group were measured. RESULTS: There
      was no significant difference in the quality of intraoperative analgesia and
      muscle relaxation between groups. The incidence of hypotension was significantly
      higher (55% vs. 20%, P < 0.005) and the need for ephedrine less in group R15 than
      in group SR10. In group SR10, the onset of motor block was delayed (2.9 +/- 1.1
      vs. 4.6 +/- 2.5 min, P < 0.005), the duration was shorter (65.9 +/- 15.1 vs.
      125.4 +/- 26.4 min, P < 0.005). The duration of effective analgesia was longer
      (260 +/- 32.5 vs. 143 +/- 22.1 min, P < 0.005), the incidence of shivering (20%
      vs. 60%, P < 0.005) and vomiting (5% vs. 30%, P < 0.005) were lower in group
      SR10. CONCLUSIONS: The combination of hyperbaric ropivacaine 10 mg with
      sufentanil 5 lg produced effective spinal anaesthesia for caesarean delivery with
      significantly less hypotension, vomiting and shivering, shorter duration of motor
      blockade and longer lasting analgesia than hyperbaric ropivacaine 15 mg.

PMID- 18617386
TI  - Controversy. Remifentanil patient-controlled analgesia should be routinely
      available for use in labour.

PMID- 18617387
TI  - A prospective study of awareness and recall associated with general anaesthesia
      for caesarean section.
AB  - BACKGROUND: The obstetric population is considered at high risk of awareness and
      recall when undergoing general anaesthesia for caesarean section. In recent years
      the incidence may have been altered by developments in obstetric anaesthesia.
      METHODS: A prospective observational study of general anaesthesia for caesarean
      section was conducted during 2005 and 2006 in 13 maternity hospitals dealing with
      approximately 49,500 deliveries per annum in Australia and New Zealand. As a
      component of this study the frequency of recall of intraoperative events was
      examined using a structured postoperative interview on two occasions. RESULTS:
      There were 1095 general anaesthetics surveyed with 47% being performed for urgent
      fetal delivery. Thiopental was the most common induction agent (83%) with
      sevoflurane being used for maintenance in 63%. In 32% of cases a depth-of
      anaesthesia monitor was used. In 763 cases (70%) there was least one
      postoperative interview enquiring into dreaming and awareness. There were two
      cases deemed to be consistent with awareness (incidence 0.26%, CI 0.03-0.9%, or 1
      in 382) and three cases of possible awareness. CONCLUSION: Awareness with recall
      of intraoperative events remains a significant complication of obstetric general
      anaesthesia but was potentially avoidable in all cases detected in this study.

PMID- 18617388
TI  - Remifentanil patient-controlled analgesia should be routinely  available for use
      in labour.

PMID- 18617389
TI  - Difficult and failed intubation in obstetric anaesthesia: an observational study
      of airway management and complications associated with general anaesthesia for
      caesarean section.
AB  - BACKGROUND: Recent developments in anaesthesia and patient demographics have
      potentially changed the practice of obstetric general anaesthesia. There are few
      contemporary data on Australasian practice of general anaesthesia for caesarean
      section, especially relating to airway management, anaesthetic techniques and
      complications. METHODS: Using a standardised case record form, a prospective
      observational study was conducted during 2005-06 in 13 maternity hospitals
      dealing with approximately 49 500 deliveries per annum. Patient demographics,
      airway management, anaesthetic techniques and major complications were evaluated
      in those given general anaesthesia. RESULTS: Data were obtained from 1095 women
      receiving general anaesthesia for caesarean section, 47% of which were classified
      as category 1 and 18% as category 4. Tracheal intubation was planned in all cases
      with rapid-sequence induction used in 97%. A grade 3 or 4 laryngoscopic view was
      obtained in 3.6 and 0.6% of cases respectively, with 3.3% considered a difficult
      intubation. There were four failed intubations (0.4%, 95% CI 0.01-0.9%), of which
      three were subsequently managed using a laryngeal mask airway. Antacid
      prophylaxis was used in 94% of elective cases and 64% of emergencies.
      Regurgitation of gastric contents was noted in eight cases (0.7%, 95% CI 0.2
      1.2%), with one confirmed case of aspiration (0.1%, 95% CI 0.002-0.5%). There
      were no cases of serious airway-related morbidity. CONCLUSIONS: General
      anaesthesia is most commonly used in emergency situations. Tracheal intubation
      after rapid-sequence induction remains the predominant approach to airway
      management in Australasia. The incidence of failed intubation is consistent with
      previous studies. Aspiration prophylaxis is not routinely used for emergency
      surgery.

PMID- 18617390
TI  - A retrospective case-controlled study of the association between request to
      discontinue second stage labor epidural analgesia and risk of instrumental
      vaginal delivery.
AB  - BACKGROUND: Epidural dose is often reduced in the second stage of labor with the
      intention of improving maternal expulsive efforts and decreasing the need for
      instrumental vaginal delivery (IVD). We conjectured that parturients requiring
      IVD would have had more analgesic interventions and requests to decrease
      analgesic density in the second stage. METHODS: This retrospective, case
      controlled study evaluated parturients with combined spinal-epidural analgesia
      and IVD over a 22-month period. Data recorded and compared between IVD and
      spontaneous delivery groups included requests to decrease the density of second
      stage analgesia and treatment of breakthrough pain. A model was developed from
      patient characteristics and analgesia interventions to predict the likelihood of
      IVD. RESULTS: Records from 2072 parturients were analyzed. The number of
      parturients in whom basal epidural infusion rate was decreased during the second
      stage of labor was greater in the IVD group (146/1021 (14.3%) vs. 51/1051 (4.9%),
      P<0.001), as was the number of parturients requiring treatment of breakthrough
      pain in the first stage of labor. Logistic regression analysis found that
      treatment for breakthrough pain was the strongest predictor of IVD. CONCLUSION:
      These results support an association between a request to reduce epidural dose in
      the second stage of labor, as well as supplemental analgesia for treatment of
      breakthrough pain, with IVD. It is unclear whether administration of more local
      anesthetic to treat breakthrough pain results in more dense motor blockade, and
      hence increases risk of IVD, or whether the decrease in infusion rate reflects
      obstetricians' dissatisfaction with the progress of obstructed labor.

PMID- 18617391
TI  - Anaesthesia for caesarean section in a patient with  Ehlers-Danlos syndrome
      associated with postural orthostatic  tachycardia syndrome.
AB  - We report the use of regional anaesthesia for elective caesarean section in a
      primigravida with hypermobility type Ehlers-Danlos syndrome (type III) associated
      with postural orthostatic tachycardia syndrome. Single-shot spinal anaesthesia
      was performed after failed epidural anaesthesia. This genotype, although
      generally associated with fewer antenatal and peripartum complications, is more
      likely than other types to display dysautonomia and orthostatic intolerance. This
      requires careful management for delivery.

PMID- 18617392
TI  - Root layers: complex regulation of developmental patterning.
AB  - Developmental patterning events involve cell fate specification and maintenance
      processes in diverse, multicellular organisms. The simple arrangement of tissue
      layers in the Arabidopsis thaliana root provides a highly tractable system for
      the study of these processes. This review highlights recent work addressing the
      patterning of root tissues focusing on the factors involved and their complex
      regulation. In the past two years studies of root patterning have indicated that
      chromatin remodeling, protein movement, transcriptional networks, and an auxin
      gradient, all contribute to the complexity inherent in developmental patterning
      events within the root. As a result, future research advances in this field will
      require tissue-specific information at both the single gene and global level.

PMID- 18617394
TI  - Enhancing patient care by the professional development of clinical staff: a self
      directed educational manual for staff working with parents with advanced cancer.

PMID- 18617393
TI  - Intratumoural FOXP3-positive regulatory T cells are associated with adverse
      prognosis in radically resected gastric cancer.
AB  - We investigated the clinical significance of tumour-infiltrating FOXP3-positive
      regulatory T cells (Tregs) in radically resected (R0) gastric cancer. From a
      single-institution database, tumors of 110 patients who underwent R0 resection
      for stage II-III disease were studied for FOXP3-positive Tregs by
      immunohistochemistry. The observed median number of FOXP3-positive Tregs was used
      as the cut-point in analyses (<6 versus >or=6 count). Tregs were significantly
      higher in gastric carcinomas than in normal tissue (P = 0.0001). Tregs count
      >or=6 was significantly associated with vascular/lymphatic/perineural invasion
      (VELIPI) in the tumour (P = 0.03). Multivariate analysis showed association
      between adverse relapse-free survival and grading 3, stage III, VELIPI and Tregs
      count >or=6 (P = 0.02). Adverse overall survival was associated with grading 3,
      stage III, VELIPI and Tregs count >or=6 (P = 0.006). FOXP3-positive Tregs may be
      a novel marker for identifying high-risk gastric cancer patients. Present
      findings deserve additional investigation as Tregs may also represent an
      innovative therapeutic target.

PMID- 18617395
TI  - Detection of melanoma micrometastases in sentinel nodes - the cons.
AB  - The sentinel node (SN) procedure in melanoma patients is important for prognostic
      information, but has no impact on survival. Micrometastases are identified in
      approximately 20% of the SNs. When a Completion Lymph Node Dissection (CLND) is
      performed for positive SN, additional non-SN lymph node involvement is also
      approximately 20%. Several classification criteria have been proposed to identify
      patients with SNs without a risk for additional nodes or a good prognosis. Micro
      anatomic analyses of metastatic SNs suggest that patients with sub
      micrometastases (<0.1mm) in the SN may be judged as SN negative. Patients with
      this limited tumor burden in their SN have an excellent prognosis and are highly
      unlikely to benefit from CLND. New techniques such as ultrasound of the lymph
      nodal basin can be promising as an alternative for SN biopsy.

PMID- 18617396
TI  - Effects of pH adjustment by parawood ash and effluent recycle ratio on the
      performance of anaerobic baffled reactors treating high sulfate wastewater.
AB  - The objective of this study was to compare the performance of anaerobic baffled
      reactor (ABR) treating concentrated rubber latex wastewater under different pH
      adjustment substances and recycling ratios (R). Two ABRs, one received wastewater
      pretreated with NaOH and the other with ash, were operated at 35 degrees C under
      identical HRTs from 10 to 1.25d. Results show that both ABRs had highest COD and
      sulfate removal efficiencies at HRT 10d (averaged 82.71% and 96.16% of ABR-NaOH,
      and 80.77% and 96.60% of ABR-Ash, respectively), where majority of the influent
      COD and sulfate were removed by the first compartment of the ABR at all
      conditions tested. Increasing R (0, 0.3 and 0.5) raised the hydraulic loading on
      the system and resulted in a drop of organic removal efficiency and methane
      yield. Translocation of sulfate reducing bacteria and methanogens in the ABRs
      caused by increased organic loading and effluent recycle is discussed. The
      results show great potential of parawood ash as a pH adjustment substance for
      acidic wastewaters.

PMID- 18617397
TI  - Imidazole piperazines: SAR and development of a potent class of cyclin-dependent
      kinase inhibitors with a novel binding mode.
AB  - A piperazine series of cyclin-dependent kinase (CDK) inhibitors have been
      identified. The compounds exhibit excellent physiochemical properties and a novel
      binding mode, whereby a bridging interaction via a water molecule with Asp 86 of
      CDK2, leads to selectivity for the CDK family of enzymes over other kinases.
      Piperazines 2e and 2i were subsequently shown to inhibit tumour growth when dosed
      orally in a nude mouse xenograft study. Additional chemical series that exploit
      this unexpected interaction with Asp 86 are also described.

PMID- 18617398
TI  - Tuberculous myelitis diagnosed by elevated adenosine deaminase activity in
      cerebrospinal fluid.

PMID- 18617399
TI  - Tyrosine hydroxylase-immunoreactive fibers in the human vagus nerve.
AB  - Sympathetic catecholaminergic fibers in the vagus nerve were
      immunohistochemically examined in formalin-fixed human cadavers using an antibody
      against the noradrenalin-synthetic enzyme tyrosine hydroxylase (TH). TH-positive
      fibers were extensively distributed in the vagal nerve components, including the
      superior and inferior ganglia, the main trunk and the branches (superior and
      recurrent laryngeal, superior and inferior cardiac, and pulmonary branches). The
      inferior ganglion and its continuous cervical main trunk contained numerous TH
      positive fibers with focal or diffuse distribution patterns in each nerve bundle.
      From these findings, we conclude that sympathetic fibers are consistently
      included in the human vagus nerve, a main source of parasympathetic preganglionic
      fibers to the cervical, thoracic and abdominal visceral organs.

PMID- 18617400
TI  - Unilateral acute foot drop due to diffuse axonal injury after head trauma.
AB  - Acute foot drop due to diffuse axonal injury (DAI) has not been previously
      described in the literature. In this report, we present a patient with unilateral
      acute foot drop caused by a DAI lesion after head trauma.

PMID- 18617401
TI  - Effects of meteorological factors on the onset of subarachnoid hemorrhage: a time
      series analysis.
AB  - Previous studies have suggested a possible association between meteorological
      factors and the onset of subarachnoid hemorrhage (SAH). We aimed to investigate
      the relationship between the onset of SAH and meteorological factors based on an
      hourly time-series analysis. We collected hourly data on transportation of
      patients with SAH using the ambulance records of the Tokyo Fire Department from
      January 1 to December 31, 2005. We also collected hourly meteorological data for
      Tokyo from the Japan Meteorological Agency during the same period. We performed a
      time-series analysis using the autoregressive integrated moving average (ARIMA)
      model to control for autocorrelations in the time-series data. There were 1729
      patients with SAH (mean age 63.3 years; 60.2% women). We identified two circadian
      patterns in the onset of SAH: a daily peak at 10 am (p<0.001) and a seasonal peak
      in February (p<0.001). Based on the ARIMA time-series analysis, significant risk
      factors associated with the onset of SAH included: low temperature on the
      previous day (lag time 17h; p=0.005) and on the onset day (lag time 0h; p<0.001);
      high barometric pressure on the onset day (lag time 0h; p=0.001). Humidity was
      not associated with the onset of SAH. Among meteorological factors, low
      temperature and high barometric pressure may be risk factors for the onset of
      SAH.

PMID- 18617402
TI  - Gamma knife radiosurgery for intracanalicular acoustic neuromas.
AB  - In the present study we reviewed our long-term experience with radiosurgery for
      intracanalicular acoustic neuromas. The study involved 25 patients with
      unilateral intracanalicular acoustic neuromas. The treatment volume was 0.07 to
      0.8 cm(3) (median: 0.27 cm(3)). The marginal radiation dose used for treatment
      was 12 Gy for all patients. The follow-up period ranged from 36 to 132 months
      (mean: 89 months). The actuarial rate of tumour growth control at 5 and 10 years
      after radiosurgery was 96%. Hearing preservation was achieved in 16 patients
      (64%) and improvement (>20 dB relative to presurgical values) was noted in one
      patient (4%). No patients experienced post-radiosurgery facial palsy or other
      cranial nerve deficits. Based on our study and long-term follow-up, radiosurgery
      can produce high rates of tumour growth control and hearing preservation for
      intracanalicular acoustic neuromas, and is an alternative to surgical resection
      given its low level of invasiveness. When determining treatment for
      intracanalicular acoustic neuromas, the condition's benign natural course and the
      likelihood of hearing preservation must be taken into account.

PMID- 18617404
TI  - Cerebral aspergillosis complicated by intracerebral haemorrhage.
AB  - Aspergillus infection can cause a wide variety of clinical syndromes. We report
      on an immunocompromised man who had a catastrophic intracerebral haemorrhage
      secondary to cerebral aspergillosis. This report highlights the need for systemic
      evaluations of the role of neurosurgery in the treatment of cerebral
      aspergillosis.

PMID- 18617405
TI  - Prognostic value of intra-operative lateral spread response monitoring during
      microvascular decompression in patients with hemifacial spasm.
AB  - Hemifacial spasm (HFS) has characteristic and specific electrophysiological
      features, primarily the lateral spread response (LSR). The aim of this study was
      to evaluate the correlation between changes in the lateral spread response during
      microvascular decompression (MVD) and the clinical outcome after MVD. Seventy-two
      patients with HFS who were treated with MVD were included in this study. Intra
      operative facial electromyography (EMG) was performed and brainstem auditory
      evoked potentials were monitored. In 32 (44.4%) patients, the LSR persisted after
      MVD. Among these 32 patients, 11 had mild HFS at discharge and six had mild HFS
      at the 6 month follow up. Out of the 40 patients in whom the LSR disappeared
      intra-operatively after MVD, five had mild HFS at discharge and four had mild HFS
      at the 6-moth follow up. The clinical outcome of HFS after MVD does not always
      correlate with intra-operative EMG abnormality. Therefore, the prognostic value
      of intra-operative LSR monitoring with respect to long-term results is
      questionable.

PMID- 18617406
TI  - Is there sentinel demyelination before development of primary CNS lymphoma?

PMID- 18617407
TI  - Relationship of neural stem cells with their vascular niche: implications in the
      malignant progression of gliomas.
AB  - During embryogenesis and in regions of the adult brain undergoing post-natal
      neurogenesis, neural stem cells and endothelial precursors are found within a
      vascular niche, where the coordinated interactions between neurogenesis and
      vasculogenesis dictates development and responses to the environment. Moreover,
      recent evidence suggests that gliomas may arise from transformed neural stem
      cells and that angiogenesis is important in the malignant progression of these
      tumors. Taken together, these findings have led researchers to focus on the
      dynamic interaction between neural stem cells and their vascular niche so as to
      find new therapeutic strategies to halt the progression of gliomas. This review
      summarizes the cellular substrates responsible for the coordinated interactions
      between the nervous and vascular systems and how this relates to gliomagenesis.

PMID- 18617408
TI  - Acute retrocollis associated with medullary arteriovenous malformation.

PMID- 18617409
TI  - Is the G2019S LRRK2 mutation common in all southern European populations?
AB  - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, especially the G2019S
      mutation, have been identified as a common cause of Parkinson's disease in
      southern European and other Mediterranean populations (Iberians, Ashkenazi Jews
      and North African Arabs). Owing to the geographic and historic vicinity of Greece
      with areas of high prevalence of LRRK2 mutations we studied the frequency of the
      G2019S mutation in a well characterized cohort of familial and sporadic
      Parkinson's disease patients of Greek origin from mainland Greece. The prevalence
      of the LRRK2 R1441C mutation and the G2385R Asian polymorphism was also
      determined. We identified no patients with any of the studied
      mutations/polymorphisms. Very low prevalence of the LRRK2 G2019S mutation has
      been reported in other southern European populations. LRRK2 mutations appear to
      be limited in certain populations and differing ancestry and founder effects may
      explain the reported variability. Accurate estimations of the frequency and
      penetrance of different LRRK2 mutations are essential for correct and cost
      efficient use of genetic testing and proper genetic counseling of patients with
      Parkinson's disease.

PMID- 18617410
TI  - Continuous single motor unit electromyographic activity in adefovir associated
      myopathy.

PMID- 18617411
TI  - Survival of patients following neurosurgical treatment of colorectal
      adenocarcinoma metastasis in the Northern Sydney-Central Coast area.
AB  - Cerebral metastases from gastrointestinal primaries constitute about 3-5% of
      surgically resected brain secondaries. There has been a paucity of regional and
      worldwide data concerning the survival and clinical course of patients undergoing
      neurosurgical treatment of cerebral metastases from colorectal origin. The
      clinical course and survival of 32 patients undergoing neurosurgical intervention
      for colorectal carcinoma metastases between 1999 and 2007 was examined. The 21
      male and 11 female patients examined had a median age of 61.8 years at diagnosis
      of colorectal cancer; median interval between colorectal cancer diagnosis and
      cerebral metastatic disease was 27.6 months; and 88% of patients underwent
      microsurgical resection. Median survival from neurosurgical intervention was 7.5
      months. Perioperative mortality was 3%. Age, gender and infratentorial location
      of lesions had no significant impact on survival. Patients undergoing whole brain
      radiotherapy (WBRT) had a significantly longer survival than those not
      undertaking this treatment (median survival 10.6 vs. 5.2 months, p = 0.018). A
      randomised, controlled trial of the utility of WBRT following surgical resection
      in this tumour subtype seems appropriate.

PMID- 18617412
TI  - Is histological diagnosis necessary to start treatment for germ cell tumours in
      the pineal region?
AB  - The significance of histological diagnosis was retrospectively investigated in
      the treatment of 79 consecutive patients with pineal region tumours. Histological
      diagnoses were consistent with clinical diagnoses in 38 out of 39 patients with
      germ cell tumours and in all eight patients with non-germ cell tumours. The
      single exception was pineoblastoma. Forty-one patients were treated under a
      clinical diagnosis of pineal germ cell tumour using neoadjuvant chemotherapy and
      radiation therapy without histological verification. Of the 41 patients, 32
      achieved an excellent response, whereas nine required the delayed resection of a
      residual tumour. Of these nine tumours, seven were mature or immature teratomas
      or scars. These patients had elevated levels of tumour markers. Most cases of
      pineal germ cell tumour could be identified on the basis of clinical findings
      only, and could be treated appropriately using neoadjuvant chemotherapy and
      radiation therapy without histological diagnosis. However, second-look surgery
      should be considered in cases with residual teratomatous components or unusual
      responses.

PMID- 18617413
TI  - John Eccles (1903-97) and the experiment that proved chemical synaptic
      transmission in the central nervous system.
AB  - One of the most important experiments in neurophysiology in the twentieth century
      took place in the physiology laboratories at the University of Otago, New
      Zealand, in August 1951. The group of researchers led by John Eccles convincingly
      established that synaptic transmission in the central nervous system was a
      chemical process. This work was the culmination of a long debate between
      advocates of electrical and chemical transmission. The conclusions overturned
      Eccles's previous theories of an electrical "Golgi-cell" mechanism and represent
      a pivotal moment in the history of neuroscience.

PMID- 18617414
TI  - Selective alkylation of beta(II)-tubulin and thioredoxin-1 by structurally
      related subsets of aryl chloroethylureas leading to either anti-microtubules or
      redox modulating agents.
AB  - Aryl chloroethylureas (CEUs) are potent anti-neoplastic agents alkylating
      specific intracellular proteins such as beta(II)-tubulin. Recently we have
      identified a new subset of CEU derived from compound 36 that alkylates
      thioredoxin isoform 1 (Trx-1), inhibits the nuclear translocation of Trx-1, and
      favors the accumulation of cells in G(0)/G(1) phase. We have evaluated the
      effects of various substituents and their position on the aromatic ring of a
      series of derivatives of 36 on (i) the anti-proliferative activity, (ii) the cell
      cycle progression, (iii) the nuclear translocation of Trx-1, and (iv) their
      covalent binding to beta-tubulin. The same experiments were performed on
      representative CEU derivatives where the 2-chloroethyl amino moiety is replaced
      by either an ethyl, a 2-aminooxazolinyl or a 2-chloroacetyl group. On one hand,
      our results suggest that CEUs substituted on the phenyl ring at position 3 or 4
      by cycloalkyl and substituted cycloalkyl or cycloalkoxy groups inhibit the
      nuclear translocation of Trx-1 and arrest the cell cycle progression in
      G(0)/G(1). On the other hand, CEUs substituted by a fused aromatic ring, an
      aliphatic chain, or a fused aliphatic ring are alkylating beta(II)-tubulin but
      not Trx-1. Beside the expected inactivity of the ethylurea derivatives, none of
      the modification to the electrophilic moiety led to cross-selectivity of the
      drugs toward beta-tubulin but increased the anti-proliferative activity and
      resulted in mitigated effects on Trx-1 translocation.

PMID- 18617415
TI  - Single-stranded DNA aptamers specific for antibiotics tetracyclines.
AB  - Tetracyclines (TCs) are a group of antibiotics comprising of a common
      tetracycline (TET) nucleus with variable X(1) and X(2) positions on 5 and 6
      carbon atoms, such as oxytetracycline (OTC) and doxycycline (DOX). In this study,
      the tetracycline group specific (TGS) ssDNA aptamers were identified by modified
      SELEX method by employing tosylactivated magnetic beads (TMB) coated with OTC,
      TET, and DOX, respectively, as targets and counter targets. Twenty TGS-aptamers
      were selected, of which seven aptamers, designated as T7, T15, T19, T20, T22,
      T23, and T24, showed high affinity to the basic TET backbone (K(d)=63-483 nM).
      The specificity of these TGS-aptamers to structural analogues followed the order
      in which the TCs was employed during SELEX process (OTC>TET>DOX) except aptamer
      T22, which was highly specific to TET than OTC or DOX. Aptamers that were
      specific to one target molecule but fail to bind the other structurally related
      TCs were eliminated during counter selection steps. Three aptamers, T7, T19, and
      T23 contained palindromic consensus sequence motif GGTGTGG. The remaining TGS
      aptamers showed many consensus sequences that are truncated forms of this
      palindrome forming mirror image or inverted sequences. For example, GTGG or its
      inverted form, GGTG motif was found in all TGS-aptamers. A consensus sequence
      motif TGTGCT or its truncated terminal T-residue was found in most TGS-aptamers,
      which is predicted to be essential for high affinity and group specificity. These
      TGS-aptamers have potential applications such as target drug delivery, and
      detection of TCs in pharmaceutical preparations and contaminated food products.

PMID- 18617416
TI  - Effect of sugars on amino acid transport by symbiotic Chlorella.
AB  - Symbiotic Chlorella F36-ZK isolated from Paramecium bursaria F36 has constitutive
      amino acid transport systems, whereas free-living Chlorella does not. We found
      that in symbiotic algae, the rate of serine (Ser) uptake increased in the
      presence of glucose (Glc) and non-metabolisable analogues, whilst incorporation
      of Ser into protein was not affected. The activation did not involve new protein
      synthesis and was enhanced under alkaline conditions. An increase in the rate of
      Ser transport resulted from Glc treatment even when pulsed for only 1 min at low
      concentrations (EC(50)=3 microM). No uptake of Glc itself was observed in F36-ZK.
      Thus, the transport signal appears to be transmitted via a glucose sensing and
      signalling pathway. Many Glc-related compounds also increased the rate of Ser
      uptake without an additive effect, suggesting recognition of these sugars by the
      same receptor and providing some insight into features of the structure-activity
      relationship. Ser uptake by F36-ZK is inhibited by Ca(2+), which is typically
      considered to be a positive modulator of amino acid uptake. Given that Glc
      restored Ser uptake from inhibition by Ca(2+), we propose that this compound is
      possibly involved in regulation of amino acid transport in this symbiotic
      relationship.

PMID- 18617417
TI  - A morphology-related study on photodegradation of protein fibres.
AB  - The wool fibre has a complex morphology, consisting of an outer layer of cuticle
      scales surrounding an inner cortex. These two components are hard to separate
      effectively except by using harsh chemical treatments, making it difficult to
      determine the susceptibility of the different components of the fibre to
      photoyellowing. An approach to this problem based on mechanical fibre
      modification is described. To expose the inner cortex of wool to different
      degrees, clean wool fibres were converted into 'powders' of various fineness via
      mechanical chopping, air-jet milling, ball milling or their combination. Four
      types of powdered wool (samples A, B, C and D) were produced with reducing
      particle size distributions and an increasing level of surface damage as observed
      using SEM. Sample A contained essentially intact short fibre snippets and sample
      D contained a large amount of exposed cortical materials. Samples B and C
      contained a mixture of short fibre snippets and cortical materials. Solid wool
      discs were then compressed from the corresponding powder samples in a polished
      stainless steel die to enable colour measurement and UV irradiation studies. ATR
      FTIR studies on powder discs demonstrated a small shift in the amide I band from
      1644cm(-1) for disc A to 1654cm(-1) for disc D due to the different structures of
      the wool cuticle and cortex, in agreement with previous studies. Similarly an
      increase in the intensity ratio of the amide I to amide II band (1540cm(-1)) was
      observed for disc D, which contains a higher fraction of cortical material at the
      surface of the disc. Discs prepared from sample D appeared the lightest in colour
      before exposure and had the slowest photoyellowing rate, whereas discs made from
      powders A-C with a higher level of cuticle coverage were more yellow before
      exposure and experienced a faster rate of photoyellowing. This suggests that the
      yellow chromophores of wool may be more prevalent in cuticle scales, and that
      wool photoyellowing occurs to a greater extent in the cuticle than in the cortex.
      Photo-induced chemiluminescence measurements showed that sample D had a higher
      chemiluminescence intensity after exposure to UVA radiation and a faster decay
      rate than samples A and B. Thus one of the roles of the wool cuticle may be to
      protect the cortex by quenching of free radical oxidation during exposure to the
      UV wavelengths present in sunlight.

PMID- 18617419
TI  - Effects of trunk muscle fatigue and load timing on spinal responses during sudden
      hand loading.
AB  - The purpose of this study was to investigate the responses of the spine during
      sudden loading in the presence of back and abdominal muscle fatigue, with a
      primary focus on the implications for spinal stability. Fifteen females were
      studied and each received sudden loads to the hands, at both known and unknown
      times. Participants received these loading trials (a) while rested, (b) with back
      muscle fatigue, and (c) with a combination of back and abdominal muscle fatigue.
      Measures were taken on the EMG activity of two trunk extensor and two abdominal
      muscles, and on the trunk angle and centre of pressure. A 3x2 Repeated Measures
      ANOVA was also performed. There were no preparations made prior to the
      perturbation even when it could be anticipated. However, the peak responses that
      followed were greater in the unexpected versus the expected condition. In
      addition, trunk muscle fatigue led to an increase in the baseline activity of the
      trunk muscles but no additional increase in activity just prior to loading. There
      was increased activation of both (opposing) muscle groups when only one muscle
      group was fatigued. Because the peak responses following the perturbation were
      enhanced in the unknown timing condition, preparations must have taken place
      prior to the anticipated perturbations, perhaps in other segments of the body
      that were not measured. Also, the load impact may not have been great enough to
      elicit large preparations. The heightened baseline activity with fatigue suggests
      that there may have been increased spinal stiffness whenever the spine was
      fatigued, and not just immediately prior to an impending perturbation. The
      increased activation of opposing muscle groups is evidence of increased
      cocontraction in response to fatigue, possibly to maintain stability with
      decreasing coordination.

PMID- 18617418
TI  - ADMA induces monocyte adhesion via activation of chemokine receptors in cultured
      THP-1 cells.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, is also an
      important inflammatory factor contributing to the development of atherosclerosis
      (AS). The present study was to test the effect of ADMA on angiotensin (Ang) II
      induced monocytic adhesion. Human monocytoid cells (THP-1) or isolated peripheral
      blood monocyte cells (PBMCs) were incubated with Ang II (10(-6)M) or exogenous
      ADMA (30 microM) for 4 or 24h in the absence or presence of losartan or
      antioxidant PDTC. In cultured THP-1 cells, Ang II (10(-6)M) for 24h elevated the
      level of ADMA in the medium, upregulated the protein expression of protein
      arginine methyltransferase (PRMT) and decreased the activity of dimethylarginine
      dimethylaminohydrolase (DDAH). Both of Ang II and ADMA increased monocytic
      adhesion to human umbilical vein endothelial cells (HUVECs), elevated the levels
      of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and tumor
      necrosis factor (TNF)-alpha and upregulated CCR(2) and CXCR(2) mRNA expression,
      concomitantly with increase in reactive oxygen species (ROS) generation and
      activation of nuclear factor (NF)-kappaB. Pretreatment with losartan (10 microM)
      or PDTC (10 microM) abolished the effects mediated by Ang II or ADMA. In isolated
      PBMCs from healthy individuals, ADMA upregulated the expression of CXCR(2) mRNA,
      which was attenuated by losartan (10 microM), however, ADMA had no effect on
      surface protein expression of CCR(2). The present results suggest that ADMA may
      be involved in monocytic adhesion induced by Ang II via activation of chemokine
      receptors by ROS/NF-kappaB pathway.

PMID- 18617420
TI  - Fractal analysis of surface electromyography signals: a novel power spectrum
      based method.
AB  - This paper presents a novel power spectrum-based method for fractal analysis of
      surface electromyography signals. This method, named the bi-phase power spectrum
      method, provides a bi-phase power-law which represents a multi-scale
      statistically self-affine signal. This form of statistical self-affinity provides
      an accurate approximation for stochastic signals originating from a strong non
      linear combination of a number of similar distributions, such as surface
      electromyography signals which are formed by the summation of a number of single
      muscle fiber action potentials. This power-law is characterized by a set of
      spectral indicators, which are related to distributional and geometrical
      characteristics of the electromyography signal's interference pattern. These
      novel spectral indicators are capable of sensing the effects of motor units'
      recruitment and shape separately by exploiting the geometry of the interference
      pattern. The bi-phase power spectrum method is compared to geometrical techniques
      and the 1/f(alpha) approach for fractal analysis of electromyography signals. The
      extracted indicators using the bi-phase power spectrum method are evaluated in
      the context of force and joint angle and the results of a human study are
      presented. Results demonstrate that the bi-phase power spectrum method provides
      reliable information, consisting of components capable of sensing force and joint
      angle effects separately, which could be used as complementary information for
      confounded conventional measures.

PMID- 18617422
TI  - Enhanced EEG gamma-band activity reflects multisensory semantic matching in
      visual-to-auditory object priming.
AB  - An important step in perceptual processing is the integration of information from
      different sensory modalities into a coherent percept. It has been suggested that
      such crossmodal binding might be achieved by transient synchronization of neurons
      from different modalities in the gamma-frequency range (>30 Hz). Here we employed
      a crossmodal priming paradigm, modulating the semantic congruency between visual
      auditory natural object stimulus pairs, during the recording of the high density
      electroencephalogram (EEG). Subjects performed a semantic categorization task.
      Analysis of the behavioral data showed a crossmodal priming effect (facilitated
      auditory object recognition) in response to semantically congruent stimuli.
      Differences in event-related potentials (ERP) were found between 250 and 350 ms,
      which were localized to left middle temporal gyrus (BA 21) using a distributed
      linear source model. Early gamma-band activity (40-50 Hz) was increased between
      120 ms and 180 ms following auditory stimulus onset for semantically congruent
      stimulus pairs. Source reconstruction for this gamma-band response revealed a
      maximal increase in left middle temporal gyrus (BA 21), an area known to be
      related to the processing of both complex auditory stimuli and multisensory
      processing. The data support the hypothesis that oscillatory activity in the
      gamma-band reflects crossmodal semantic-matching processes in multisensory
      convergence sites.

PMID- 18617421
TI  - Quantitative tractography metrics of white matter integrity in diffusion-tensor
      MRI.
AB  - We present new quantitative diffusion-tensor imaging (DTI) tractography-based
      metrics for assessing cerebral white matter integrity. These metrics extend prior
      work in this area. Tractography models of cerebral white matter were produced
      from each subject's DTI data. The models are a set of curves (e.g.,
      "streamtubes") derived from DTI data that represent the underlying topography of
      the cerebral white matter. Nine metrics were calculated in whole brain
      tractography models and in three "tracts-of-interest": transcallosal fibers and
      the left and right cingulum bundles. The metrics included the number of
      streamtubes and several other based on the summed length of streamtubes,
      including some that were weighted by scalar anisotropy metrics and normalized for
      estimated intracranial volume. We then tested whether patients with subcortical
      ischemic vascular disease (i.e., vascular cognitive impairment or VCI) vs.
      healthy controls (HC) differed on the metrics. The metrics were significantly
      lower in the VCI group in whole brain and in transcallosal fibers but not in the
      left or right cingulum bundles. The metrics correlated significantly with
      cognitive functions known to be impacted by white matter abnormalities (e.g.,
      processing speed) but not with those more strongly impacted by cortical disease
      (e.g., naming). These new metrics help bridge the gap between DTI tractography
      and scalar analytical methods and provide a potential means for examining group
      differences in white matter integrity in specific tracts-of-interest.

PMID- 18617423
TI  - Mapping of the norepinephrine transporter in the human brain using PET with (S,S)
      [18F]FMeNER-D2.
AB  - We have evaluated the detailed mapping of the norepinephrine transporter (NET) in
      the human brain with (S,S)-[(18)F]FMeNER-D(2) using a template method and the
      generation of functional ROIs based on the PET information. Brain PET
      measurements were performed from 90 to 210 min after the injection of (S,S)
      [(18)F]FMeNER-D(2) in 20 healthy male subjects. Binding potential (BP(ND)) was
      calculated as late time ratio of the target region to the reference region
      (caudate) minus one. BP(ND) template images were generated from mean parametric
      images obtained in a group of 10 subjects using SPM2. On the BP(ND)/MRI template
      images, functional ROIs based on several different BP(ND) thresholds for the
      thalamus and brainstem were generated automatically using PMOD 2.8 software in
      addition to anatomical ROIs. PET/MRI data of another group of 10 subjects were
      used to evaluate the validity of the template method and the functional ROIs. NET
      BP(ND) template images demonstrated higher binding in the medial thalamus whereas
      the anterior and the pulvinar divisions had lower binding. In the brainstem, high
      binding was detected around the cerebral aqueduct of the midbrain and within the
      dorsal pons, in a volume comprising locus coeruleus. Functional ROIs with higher
      BP(ND) thresholds naturally yielded higher BP(ND) and lower coefficients of
      variance than did anatomical ROIs. This study indicated that (S,S)-[(18)F]FMeNER
      D(2) combined with a template method provides detailed information on the
      distribution of NET in vivo and that functional ROIs on the template would be
      useful in further clinical studies.

PMID- 18617424
TI  - The signaling protein Wnt4 enhances thymopoiesis and expands multipotent
      hematopoietic progenitors through beta-catenin-independent signaling.
AB  - Despite studies based on deletion or activation of intracellular components of
      the canonical Wingless related (Wnt) pathway, the role of Wnts in
      hematolymphopoiesis remains controversial. Using gain-of-function and loss-of
      function models, we found that Wnt4 differentially affected diverse subsets of
      hematopoietic stem and progenitor cells. Bone-marrow and thymic Lin(
      )Sca1(+)Kit(hi) cells (LSKs) were the key targets of Wnt4. In adult mice, Wnt4
      induced expansion of Flt3(+) bone-marrow LSKs (lymphoid-primed multipotent
      progenitors) led to a sizeable accumulation of the most immature thymocyte
      subsets (upstream of beta-selection) and a major increase in thymopoiesis.
      Conversely, Wnt4(-/-) neonates showed low frequencies of bone-marrow LSKs and
      thymic hypocellularity. We provide compelling evidence that Wnt4 activates
      noncanonical (beta-catenin-independent) signaling and that its effects on
      hematopoietic cells are mainly non-cell-autonomous. Our work shows that Wnt4
      overexpression has a unique ability to expand Flt3(+) LSKs in adults and
      demonstrates that noncanonical Wnt signaling regulates thymopoiesis.

PMID- 18617425
TI  - Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic
      inflammation.
AB  - Adaptive Foxp3(+) regulatory T (Treg) cells develop during induction of mucosal
      tolerance and after immunization. Large numbers of Foxp3(+) T cells have been
      found in inflamed tissues. We investigated the role of adaptive Foxp3(+) Treg
      cells in mucosal tolerance and in chronic allergic lung inflammation. We used two
      strains of mice that are devoid of naturally occurring Treg cells; one is capable
      of generating adaptive Foxp3(+) Treg cells upon exposure to antigen, whereas the
      other is deficient in both naturally occurring and adaptive Foxp3(+) Treg cells.
      We found that adaptive Foxp3(+) Treg cells were essential for establishing
      mucosal tolerance and for suppressing IL-4 production and lymphoid neogenesis in
      chronic inflammation, whereas IL-5 production and eosinophilia could be
      controlled by Foxp3-independent, IFN-gamma-dependent mechanisms. Thus, whereas
      adaptive Foxp3(+) Treg cells regulate sensitization to allergens and the severity
      of chronic inflammation, IFN-gamma-producing cells can play a beneficial role in
      inflammatory conditions involving eosinophils.

PMID- 18617427
TI  - Is early carotid stenting indicated in patients with recent neurological events?

PMID- 18617428
TI  - Interaction of anti-aggregation agent dimethylethylammonium propane sulfonate
      with acidic fibroblast growth factor.
AB  - Prevention of aggregation is critical for analyzing protein structure. Non
      detergent sulfobetaines (NDSBs) are known to prevent protein aggregation, but the
      molecular mechanisms of their anti-aggregation effect are poorly understood. To
      elucidate the underlying mechanisms, we analyzed the effects of
      dimethylethylammonium propane sulfonate (NDSB-195) on acidic fibroblast growth
      factor (aFGF). NDSB-195 (0.5M) increased both aggregation and denaturation
      temperatures of aFGF by 4 degrees C. Chemical shift perturbation analyses
      indicated that many affected residues were located at the junction between a beta
      strand (or 3(10)-helix) and a loop, irrespective of the chemical properties of
      the residue. The apparent dissociation constants of the interaction ranged from
      0.04 to 3M, indicating weak interactions between NDSB and protein molecules.

PMID- 18617429
TI  - An analysis of the factors that influence the level and scaling of mammalian BMR.
AB  - The factors influencing the basal rate of metabolism (BMR) in 639 species of
      mammals include body mass, food habits, climate, habitat, substrate, a
      restriction to islands or highlands, use of torpor, and type of reproduction.
      They collectively account for 98.8% of the variation in mammalian BMR, but often
      interact in complex ways. The factor with the greatest impact on BMR, as always,
      is body mass (accounting for 96.8% of its variation), the extent of its impact
      reflecting the 10(6.17)-fold range of mass in measured species. The attempt to
      derive mathematically the power relationship of BMR in mammals is complicated by
      the necessity to include all of the factors that influence BMR that are
      themselves correlated with body mass. BMR also correlates with taxonomic
      affiliation because many taxa are distinguished by their ecological and
      behavioral characteristics. Phylogeny, reflecting previous commitments, may
      influence BMR either through a restriction on the realized range of behaviors or
      by opening new behavioral and ecological opportunities. A new opportunity
      resulted from the evolution by eutherians of a type of reproduction that
      permitted species feeding on high quality resources to have high BMRs. These
      rates facilitated high rates of gas, nutrient, and waste exchange between a
      pregnant eutherian and her placental offspring. This pattern led to high rates of
      reproduction in some eutherians, a response denied all monotremes and marsupials,
      thereby permitting eutherians to occupy cold-temperate and polar environments and
      to dominate other mammals in all environments to which ecologically equivalent
      eutherians had access.

PMID- 18617426
TI  - The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell
      response to respiratory virus infections.
AB  - Innate recognition of invading pathogens in peripheral tissues results in the
      recruitment of circulating memory CD8(+) T cells to sites of localized
      inflammation during the early phase of a recall response. However, the mechanisms
      that control the rapid recruitment of these cells to peripheral sites are poorly
      understood, particularly in relation to influenza and parainfluenza infections of
      the respiratory tract. In this study, we demonstrate a crucial role for C-C
      chemokine receptor 5 (CCR5) in the accelerated recruitment of memory CD8(+) T
      cells to the lung airways during virus challenge. Most importantly, CCR5
      deficiency resulted in decreased recruitment of memory T cells expressing key
      effector molecules and impaired control of virus replication during the initial
      stages of a secondary response. These data highlight the critical importance of
      early memory T cell recruitment for the efficacy of cellular immunity in the
      lung.

PMID- 18617430
TI  - A determination of the pre-analytical storage conditions for insulin like growth
      factor-I and type III procollagen peptide.
AB  - OBJECTIVE: IGF-I and type III procollagen (P-III-P) have been proposed as markers
      to detect GH abuse. This study aims to determine whether the pre-analytical
      storage temperature or delayed centrifugation affect the measured IGF-I and P-III
      P concentrations. DESIGN: Observational study. SETTING: Wellcome Trust Clinical
      Research Facility, Southampton. SUBJECTS: Nineteen healthy volunteers.
      INTERVENTION: Blood was collected into bottles containing a clotting agent,
      lithium heparin or EDTA. One sample from each group was centrifuged and stored at
      -80 degrees C (control sample). The remaining samples from each group were stored
      as either serum or whole blood at 4 degrees C or room temperature for up to five
      days prior to storage at -80 degrees C. OUTCOME MEASURES: IGF-I and P-III-P.
      RESULTS: The storage temperature or timing of centrifugation did not appear to
      affect IGF-I concentration. In contrast, the measured P-III-P concentration rose
      by 6.5-7% per day in clotted and lithium heparin samples when stored as whole
      blood (p<0.006) or serum (6.2-6.5% per day) at room temperature (p<0.001). P-III
      P did not change when the samples were stored at 4 degrees C. Although collection
      into EDTA inhibited the rise in P-III-P, the baseline measured values were
      significantly higher than in other media and spiking experiments demonstrated
      that EDTA exerted a significant matrix effect on the assay. CONCLUSION: While the
      optimum collection method is immediate centrifugation and storage at -80 degrees
      C, it would seem acceptable to store serum or clotted blood samples at 4 degrees
      C, but not ambient temperature, for up to five days. It is incumbent on the anti
      doping authorities to provide facilities to allow this.

PMID- 18617431
TI  - Prevalence of risk factors for referring post-menopausal women for bone
      densitometry. The INSTANT study.
AB  - BACKGROUND: Measurement of bone density by densitometry is an appropriate public
      health strategy for prevention of osteoporotic fractures in at-risk individuals,
      and physicians are encouraged to screen for these risk factors in post-menopausal
      women. OBJECTIVE: To determine the frequency of risk factors for osteoporosis in
      a representative sample of the French general population in order to estimate the
      number of women eligible for bone densitometry. METHODS: A cross-sectional
      epidemiological survey of osteoporosis in 2081 post-menopausal women over 45
      years in the general population was conducted using a stratified random sampling
      method and face-to-face interviews. Information was collected on personal or
      family history of vertebral fracture or limb fracture, endocrine disorders,
      corticosteroid use, and early menopause. Body mass index was determined during
      the interview by measuring height and weight. RESULTS: A total of 1041 women
      interviewed (51.8%) reported at least one risk factor for osteoporosis and would
      thus be eligible for densitometry. The most frequently reported risk factor was
      vertebral fracture or collapse (20.8%), followed by endocrine disorders (10.5%)
      and long-term corticosteroid treatment (10.5%). The prevalence of vertebral and
      limb fracture increased with age. Multiple risk factors were reported by 381
      women and the proportion of women presenting multiple risk factors increased with
      age. CONCLUSIONS: Extrapolated to the general population, over five million women
      in France would be eligible for densitometry. Since only a small proportion of
      these currently receive a diagnosis of osteoporosis, a considerable number of
      women could thus potentially benefit from more widespread use of densitometry.

PMID- 18617432
TI  - A multivariate study of the performance of an ultrasound-assisted madder dyes
      extraction and characterization by liquid chromatography-photodiode array
      detection.
AB  - An extraction method of madder (Rubia tinctorum) roots dyes is established and
      optimized to obtain the original chemical composition. A central composite design
      (CCD) was developed to specify the importance of the three major factors studied
      (time, temperature and solvent composition) affecting the ultrasound-assisted
      extraction of this matrix. A preliminary granulometric study of madder roots is
      realized in the aim to determine the optimal particles size corresponding to the
      best ultrasound effects. A comparison with the classical extraction method of
      madder dyes by reflux is described. The identification of the constituents of R.
      tinctorum is carried out by liquid chromatography coupled with a photodiode array
      detector (LC-PDA). Anthraquinonic aglycone and heterosidic dyes compounds are
      characterized by retention time and UV spectrum: alizarin (1,2
      dihydroxyanthraquinone), purpurin (1,2,4-trihydroxyanthraquinone), lucidin (1,3
      dihydroxy-2-hydroxymethylanthraquinone), rubiadin (1,3-dihydroxy-2
      methylanthraquinone), xanthopurpurin (1,3-dihydroxyanthraquinone), pseudopurpurin
      (1,2,4-trihydroxy-3-carboxyanthraquinone), lucidin primeveroside, ruberythric
      acid (alizarin primeveroside), galiosin (pseudopurpurin primeveroside) and
      rubiadin primeveroside. The optimal experimental conditions are 18min, 36 degrees
      C and 37/63 MeOH/H(2)O (v/v).

PMID- 18617433
TI  - Boundary crossers, communities, and health: exploring the role of rural health
      professionals.
AB  - Boundary crossers understand the culture and language of community and health
      service domains and have the trust of both. Rural health professionals living
      within the communities they serve are ideally placed to harness community
      capacity so as to influence community-level determinants of health. We analyse
      five case studies of rural health professionals acting as boundary crossers
      against indicators of capacity for communities and external agents such as health
      services working in partnership. A more explicit evidence base for inclusion of
      community health development in the jobs of rural health professionals is needed.

PMID- 18617434
TI  - The effect of a vastus lateralis tape on muscle activity during stair climbing.
AB  - Recently taping techniques with the primary purpose of altering muscle activity
      have become a part of clinical physiotherapy practice. A firmly applied tape
      across the fibres of the vastus lateralis (VL) muscle has been proposed to
      decrease the VL muscle activity. The primary aim of this study was to assess the
      effects of an inhibitory muscle tape applied over the vastus lateralis (VL)
      muscle during stair climbing. Twenty five subjects without lower limb pathology
      were recruited. Normalised integrated EMG (IEMG) was analysed from VL, vastus
      medialis obliquus (VMO), biceps femoris (BF) and soleus muscles during stair
      climbing. The subjects were assessed during three conditions: no tape (untaped),
      (no tension) control tape and (tensioned tape) VL inhibitory taping application.
      There was a significant decrease (p<0.05) in the VL IEMG during the initial
      stance phase during both stair ascent and descent. The inhibition if the VL
      muscle occurred with both control and VL inhibitory tape applied. No significant
      differences (p>0.05) were noted in any of the other muscles assessed. The results
      demonstrated that there was a significant decrease in the IEMG of the VL both
      during stair ascent and descent with VL inhibitory tape and control tape applied
      in normal subjects.

PMID- 18617435
TI  - Histone deacetylase inhibitors and hemoglobin F induction in beta-thalassemia.
AB  - Epigenomic modifiers, such as histone deacetylase inhibitors, are compounds that
      regulate gene expression by interfering with the enzymatic machinery that
      maintains the proper chromatin structure of the nucleus. These compounds are at
      the forefront of novel therapeutic agents for the treatment of several diseases
      including cancer and genetic disorders such as beta-thalassemia and sickle cell
      disease. Here we review the current understanding of the mechanism of action of
      epigenomic modifiers in the treatment of beta-thalassemia and sickle cell anemia.
      We also discuss how the lessons learned from the study of the effects of these
      compounds on the beta-globin locus, one of the best characterized regions of the
      human genome, might contribute to the understanding of the mechanism of action of
      these same compounds in cancer, where the specific regions of the genome that are
      responsible for the pathophysiology of the disease are often poorly defined.

PMID- 18617436
TI  - Axon tracking in serial block-face scanning electron microscopy.
AB  - Electron microscopy is an important modality for the analysis of neuronal
      structures in neurobiology. We address the problem of tracking axons across large
      distances in volumes acquired by serial block-face scanning electron microscopy
      (SBFSEM). Tracking, for this application, is defined as the segmentation of an
      axon that spans a volume using similar features between slices. This is a
      challenging problem due to the small cross-sectional size of axons and the low
      signal-to-noise ratio in our SBFSEM images. A carefully engineered algorithm
      using Kalman-snakes and optical flow computation is presented. Axon tracking is
      initialized with user clicks or automatically using the watershed segmentation
      algorithm, which identifies axon centers. Multiple axons are tracked from slice
      to slice through a volume, updating the positions and velocities in the model and
      providing constraints to maintain smoothness between slices. Validation results
      indicate that this algorithm can significantly speed up the task of manual axon
      tracking.

PMID- 18617437
TI  - Growth and characterization of sodium pentaborate [Na(H4B5O10)] single crystals.
AB  - The bulk single crystals of sodium pentaborate [Na(H4B5O10)] were grown by slow
      evaporation solution growth technique using deionized water as solvent. The grown
      crystal was confirmed by single crystal X-ray diffraction studies. The structural
      perfection of the grown crystals has been analyzed by high resolution X-ray
      diffraction (HRXRD) studies by recording rocking curve. The photoluminescence
      (PL), UV-vis spectral studies were performed and the optical bandgap of the
      material was calculated. The presence of the functional groups was identified by
      FT-IR measurement. The factor group analysis was done on Na(H4B5O10) to reveal
      the vibrational optical modes. The thermal and mechanical properties of the grown
      crystal were studied by TG-DTA and Vickers microhardness tester, respectively.
      The dielectric behavior of Na(H4B5O10) was investigated with different
      frequencies and temperatures.

PMID- 18617439
TI  - The use of MAPLT and MLVA analyses of phenotypically closely related isolates of
      Salmonella enterica serovar Typhimurium.
AB  - The resolving power of multiple-locus variable-number tandem repeat analysis
      (MLVA) was undertaken on 78 phenotypically closely related isolates of Salmonella
      enterica serovar Typhimurium that were previously analysed with multiple
      amplification of phage locus typing (MAPLT) and pulsed-field gel electrophoresis
      (PFGE). Isolates were tested with 10 primer sets targeting tandem repeat loci in
      the S. Typhimurium genome. A new primer set targeting the SB21(ST64B) locus was
      also assessed for MAPLT analysis. Both methods produced similar levels of
      discrimination between 41 non-DT 126 isolates while MLVA proved superior in
      separating the DT 126 isolates. Results showed that two loci, STTR5 and STTR6,
      provided the most variation in tandem repeat numbers between the 78 S.
      Typhimurium isolates with 11 alleles detected for each locus. Some isolates did
      not produce amplified product with PCR for various loci, providing another level
      for discrimination. The remaining MLVA loci provided less allelic variation, with
      4 loci failing to provide any discrimination. There were a number of isolates
      that were shown to be unique by one method but were clustered by the other
      method. Combining the most variable regions of both MAPLT and MLVA into one assay
      may provide significant resolution of isolates with the minimal number of primers
      utilised.

PMID- 18617438
TI  - Independence of restrictive filling pattern and LV ejection fraction with
      mortality in heart failure: an individual patient meta-analysis.
AB  - BACKGROUND: The Doppler echocardiographic restrictive mitral filling pattern
      (RFP) is an important prognostic indicator in patients with heart failure (HF),
      but the interaction between RFP, left ventricular ejection fraction (LVEF) and
      filling pattern remains uncertain. AIMS: To determine whether the RFP is
      predictive of mortality independently of LVEF in patients with HF. METHODS:
      Online databases were searched to identify studies assessing the relationship
      between prognosis and LV filling pattern in patients with HF. Individual patient
      data from 18 studies (3540 patients) were extracted and collated at the MeRGE
      Coordinating Centre (The University of Auckland). RESULTS: Overall, RFP was
      associated with higher all-cause mortality than the non-restrictive filling
      pattern: hazard ratio 2.42 (95% CI 2.06, 2.83). In multivariable analysis the
      RFP, LVEF, NYHA class and age were independent predictors of mortality. The
      prevalence of the RFP was inversely related to LVEF but remained a predictor of
      mortality even in those patients with preserved LVEF. CONCLUSIONS: The
      restrictive mitral filling pattern is a powerful predictor of mortality,
      independent of LVEF and age, in patients with HF. Doppler-derived LV filling
      patterns are an accessible marker from echocardiography that can readily be
      incorporated in risk stratification of all patients with HF.

PMID- 18617441
TI  - Plasmodium falciparum population dynamics: only snapshots in time?
AB  - Infections caused by the malaria parasite Plasmodium falciparum often comprise
      multiple genetically distinct clones. Individuals in endemic areas can have
      different clones detected in their peripheral blood over a few days or even
      hours. This reveals interesting within-host dynamics of multiclonal infections,
      which seem to differ in asymptomatic and symptomatic infections. As well as being
      an intriguing biological phenomenon that merits further understanding, the
      extensive dynamics of P. falciparum infections have practical implications on the
      design and interpretation of malaria studies. Most assessments will, indeed, only
      provide snapshots of the parasite population dynamics.

PMID- 18617440
TI  - Analysis of risk factors determining prognosis of cutaneous squamous-cell
      carcinoma: a prospective study.
AB  - BACKGROUND: Cutaneous squamous-cell carcinomas (SCC) are among the most common
      cancers capable of metastasis. Current Tumour Node Metastasis (TNM) staging
      includes horizontal tumour size, involvement of extradermal structures, and
      degree of differentiation. The aim of this study was to prospectively analyse the
      key factors predicting metastasis and local recurrence in cutaneous SCC. METHODS:
      We assessed prospectively investigated potential risk factors for metastasis or
      local recurrence of SCC, previously suggested by retrospective studies and small
      case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all
      patients underwent surgery for cutaneous SCC with complete histological
      examination of the three-dimensional excision margins (3D-histology) in one
      centre. Univariate and multivariate analysis included tumour thickness,
      horizontal size, body site, histological differentiation, desmoplastic growth,
      history of multiple SCC, and immunosuppression. Primary endpoints were time to
      metastasis and time to local recurrence, defined as the time from date of
      diagnosis of the primary tumour to the date of diagnosis of metastasis or local
      recurrence, respectively. FINDINGS: 653 patients were enrolled in the study. 38
      patients were lost to follow-up leaving 615 assessable patients (median age 73
      years [range 27-98]). During a median follow-up period of 43 months (range 1
      165), 26 (4%) of 615 patients developed metastases and 20 patients developed
      local recurrence (3%). Tumours 2.0 mm or less in thickness did not metastasise.
      Metastases occurred in 12 (4%) of 318 tumours between 2.1 mm and 6.0 mm in
      thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6.0 mm. On
      multivariate analysis, key prognostic factors for metastasis were increased
      tumour thickness (hazard ratio 4.79 [95% CI 2.22-10.36]; p<0.0001),
      immunosuppression (4.32 [1.62-11.52]; p=0.0035), localisation at the ear (3.61
      [1.51-8.67]; p=0.0040), and increased horizontal size (2.22 [1.18-4.15];
      p=0.0128). The risk of local recurrence depended on increased tumour thickness
      (6.03 [2.71-13.43]; p<0.0001) and desmoplasia (16.11 [6.57-39.49]; p<0.0001).
      INTERPRETATION: Only SCC greater than 2.0 mm in thickness are associated with a
      significant risk of metastasis. Tumours greater than 6.0 mm are associated with a
      high risk of metastasis and local recurrence. Desmoplastic growth is an
      independent risk factor for local recurrence. Studies should assess the role of
      follow-up visits and sentinel-lymph-node biopsy in high-risk patients.

PMID- 18617442
TI  - Current opinions on the role of pathogen reduction technology in improving the
      viral safety of blood and derivatives.

PMID- 18617443
TI  - What does it take to call it a pathogenic mutation?

PMID- 18617444
TI  - Perceived health in children presenting with a "first seizure".
AB  - The goal of this study was to determine health perceptions of children and
      parents after a "first seizure." Children 5-17 years of age referred with a first
      recognized seizure (FRS) were included in the study. Children and primary
      caregivers completed the Child Health Questionnaire. Sixty-seven of 70 (96%)
      participated (mean age=11.2, SD=3.4; 48 seizure, 19 nonseizure). Parents of
      children with a first recognized epileptic seizure (FRS-e) had significantly
      lower scores on Psychosocial Summary scores (P<0.001) and on 6 of 12 subscales.
      Children who had had their first recognized nonepileptic seizure (FRS-ne) tended
      to have poorer Parental Time-Emotional scores (P=0.05). Although children did not
      receive lower scores, they did report a change in perceived health (P=0.017).
      While parents of children presenting with a FRS report increased emotional
      impact, those with a FRS-e report more significant difficulties in several
      domains of perceived health. It is important for physicians and health care
      providers to be aware of these concerns as they might impact further
      interventions.

PMID- 18617445
TI  - On-column epimerization of dihydroartemisinin: an effective analytical approach
      to overcome the shortcomings of the International Pharmacopoeia monograph.
AB  - We developed a cryo-HPLC/UV method for the simultaneous determination of
      artemisinin (1), alpha-dihydroartemisinin (2alpha), beta-dihydroartemisinin
      (2beta), and a ubiquitous thermal decomposition product of 2 (designated as
      diketoaldehyde, 3), starting from the International Pharmacopoeia monograph on
      dihydroartemisinin. The method takes for the first time the on-column
      epimerization process of 2 into consideration. Chromatographic separation was
      obtained under reversed-phase conditions on a Symmetry C18 column (3.5 microm
      particle size) with a mobile phase consisting of acetonitrile-water 60:40 (v/v),
      delivered at 0.60-1.00 ml/min flow-rates, with ultraviolet detection at low
      wavelength (lambda = 210 nm). Low temperatures (T = 0-10 degrees C) were selected
      on the grounds of a diastereoselective dynamic HPLC (DHPLC) study performed at
      different temperatures, aimed at identifying the best experimental conditions
      capable of minimizing the on-column interconversion process.

PMID- 18617446
TI  - LC-MS metabolic profiling of Arabidopsis thaliana plant leaves and cell cultures:
      optimization of pre-LC-MS procedure parameters.
AB  - This study treats the optimization of methods for homogenizing Arabidopsis
      thaliana plant leaves as well as cell cultures, and extracting their metabolites
      for metabolomics analysis by conventional liquid chromatography electrospray
      ionization mass spectrometry (LC-ESI/MS). Absolute recovery, process efficiency
      and procedure repeatability have been compared between different pre-LC-MS
      homogenization/extraction procedures through the use of samples fortified before
      extraction with a range of representative metabolites. Hereby, the magnitude of
      the matrix effect observed in the ensuing LC-MS based metabolomics analysis was
      evaluated. Based on relative recovery and repeatability of key metabolites,
      comprehensiveness of extraction (number of m/z-retention time pairs) and clean-up
      potential of the approach (minimum matrix effects), the most appropriate sample
      pre-treatment was adopted. It combines liquid nitrogen homogenization for plant
      leaves with thermomixer based extraction using MeOH/H(2)O 80/20. As such, an
      efficient and highly reproducible LC-MS plant metabolomics set-up is achieved, as
      illustrated by the obtained results for both LC-MS (8.88%+/-5.16 versus 7.05%+/
      4.45) and technical variability (12.53%+/-11.21 versus 9.31%+/-6.65) data in a
      comparative investigation of A. thaliana plant leaves and cell cultures,
      respectively.

PMID- 18617447
TI  - The influence of internal length scales on mechanical properties in natural
      nanocomposites: a comparative study on inner layers of seashells.
AB  - Natural materials exhibit outstanding properties compared to their single
      constituents because of their hierarchical alignment. Therefore, they can be used
      as a guide to enhance the properties of artificial nanocomposite materials, which
      eventually could excel compared to their biological counterparts. In this study,
      seashells of five species with different microstructures were compared by
      correlating the sizes and aspect ratios of the building blocks to their
      mechanical behavior. The analyzed nacreous seashells were Trochus maculatus,
      Haliotis rufescens and Pteria penguin; the non-nacreous seashells were Meretrix
      lusoria and Pecten maximus. The results were used to determine the optimal values
      for the shape, size and volume fraction of the structural elements with regards
      to hardness, Young's modulus and fracture toughness. Surprisingly, the aspect
      ratio of the mineral phase in all seashells investigated was found to be close to
      the optimal value for strength as predicted by theory.

PMID- 18617448
TI  - The uncertain path/journey into and through surgical training: an overview of
      different approaches and programmes in different countries.

PMID- 18617449
TI  - Reaching our successors: the trend for early specialisation and the potential
      effect on recruitment to our speciality.

PMID- 18617450
TI  - The hidden cost of skin scars: quality of life after skin scarring.
AB  - BACKGROUND: Surprisingly little is known about how skin scars affect patients'
      lives, though specialist clinical impressions suggest their impact is related to
      both their physical and psychosocial effects. Facial scars have been shown to
      cause high levels of anxiety and self-consciousness, but further work has been
      neglected. We aimed to explore the influence of skin scars on patients' quality
      of life (QoL) and identify potential implications for clinical practice. METHODS:
      We adopted a needs-based approach to QoL and conducted semi-structured interviews
      with scar patients at a specialist clinic. Transcribed data underwent
      interpretative phenomenological analysis to identify common themes in
      individuals' personal experiences. RESULTS: Thirty-four scar patients (24 women;
      aged 14-70 years, mean=35.7 years, SD=17.9 years) with a wide range of scar type,
      severity and onset were recruited. Five hundred and seventy-three statements were
      identified from interview transcripts relating to need impairment by skin scars.
      These were subsequently classified into 44 themes covering five main areas:
      physical comfort and functioning; acceptability to self and others; social
      functioning; confidence in the nature and management of the condition; emotional
      well-being. The majority of respondents were unhappy with their scar's appearance
      due to their perceived stigma and psychological associations, and thus adopted
      different coping behaviours to hide or compensate for them. Often this made them
      unsociable and interfered with their communication skills, personal
      relationships, work life and leisure activities. Concerns about the diagnosis and
      persistent nature of scars were common, whilst unempathic management by general
      physicians and frustrations of current treatment compounded distress.
      CONCLUSIONS: There are five main areas of impact on the needs of scar patients
      that should be addressed in their management, which are greater and more complex
      than previously considered. Support services should be made available, along with
      clinician and public education to improve management and help reduce patient
      distress. A need for a carefully designed measure of scar-related QoL is also
      indicated, for use in clinical settings and trials.

PMID- 18617451
TI  - Efficacy and mechanisms of vacuum-assisted closure (VAC) therapy in promoting
      wound healing: a rodent model.
AB  - BACKGROUND: The vacuum-assisted closure device (VAC) has revolutionised wound
      care, although molecular mechanisms are not well understood. We hypothesise that
      the VAC device induces production of pro-angiogenic factors and promotes
      formation of granulation tissue and healing. METHODS: A novel rodent model of VAC
      wound healing was established. Excisional wounds were created on rat dorsa.
      Wounds were dressed with Tegaderm (control group), VAC Granulofoam and Tegaderm
      (special control group), or VAC Granulofoam, T.R.A.C. PAD((R)) with 125 mm Hg
      continuous negative pressure (VAC group). Wound closure rates were calculated as
      a percentage of initial wound sizes. Rats were sacrificed on postoperative days
      3, 5 and 7; harvested tissues were processed for histology [haematoxylin & eosin
      (H&E), Masson's trichrome, picrosirius red] and Western blot analysis (CD31,
      vascular endothelial growth factor, basic fibroblast growth factor). RESULTS:
      Statistically significant wound closure rates were achieved in the experimental
      group at all measured time points: day 3, 28.1% (VAC) vs 8.2% (control) and 8.8%
      (special control) (ANOVA, P<0.0001); day 5, 45.3% (VAC) vs 23.7% (control) and
      22.5% (special control) (ANOVA, P=0.0003); day 7, 54.4% (VAC) vs 43.0% (control)
      and 31.5% (special control) (ANOVA; P<0.0001). Morphological evaluation by
      Masson's trichrome stain showed increased collagen organisation and wound
      maturation in the VAC group. These wounds also showed increased expression of
      vascular endothelial growth factor and fibroblast growth factor-2 on day 5 by
      Western blot analysis. CONCLUSION: A small animal VAC wound model was
      established. Wounds treated with a VAC device showed accelerated wound closure
      rates, increased pro-angiogenic growth factor production and improved collagen
      deposition. Further application of this model may elucidate other mechanisms.

PMID- 18617452
TI  - Perceptions of correct preoperative storage and transfer of amputated digits: a
      national survey of referring emergency departments.

PMID- 18617453
TI  - Cross-leg fillet flap for the reconstruction of severe bilateral leg burns.
AB  - For a patient with fourth-degree burns involving both legs, we performed an
      amputation of the right leg at the thigh and covered the left knee joint with the
      posterior part of the right leg as a cross-leg fillet flap. It is reasonable to
      use tissue from one leg for reconstruction of the other leg in order to avoid
      bilateral leg amputation in the treatment of bilateral severe leg injury. We
      could transfer a sufficient amount of tissue by using this flap without donor
      site morbidity. Generally, hip or knee joint contracture is a major problem with
      the cross-leg flap. The long pedicle of this flap allowed the patient some leg
      movement and there was no contracture at his knee or hip joints. We cannot use
      this flap as a sensory flap because of pedicle cutting, but inappropriate
      sensation of the lower extremity is uncomfortable and reduces a patient's quality
      of life. The cross-leg fillet flap described here avoids donor site morbidity
      without the use of microsurgery. This flap will become a treatment option for
      severe bilateral leg injuries when one leg requires amputation.

PMID- 18617454
TI  - DIEP flap with implant: a further option in optimising breast reconstruction.
AB  - Recent advances in breast reconstruction allow for high expectations regarding
      long-term symmetry and aesthetic appearance. The DIEP flap is currently
      considered as an ideal autologous reconstruction. However, there are situations
      in which the amount of tissue from a DIEP flap is not enough to achieve adequate
      symmetry. Indications and outcomes for a combined use of DIEP flap and implants
      are discussed in order to describe and examine a further scenario in optimising
      breast reconstruction. Between January 2004 and January 2006, all patients who
      underwent combined DIEP/implant breast reconstruction have been collected and
      followed prospectively. When clinical assessment demonstrated inadequate amount
      of tissue in the abdominal region to achieve a suitable unilateral or bilateral
      reconstruction with DIEP flaps, the patients were counselled about the
      opportunity of primary augmentation of the DIEP flaps. In cases where DIEP breast
      reconstruction has been done previously and there is a considerable asymmetry,
      delayed flap augmentation was considered. Patient's age, indication for surgery,
      preoperative and postoperative radiotherapy (RT), operative procedure, implant
      size, location and timing of insertion, complications, outcomes, and follow-up
      have been gathered. In all cases, textured round silicone gel implants have been
      used. After 12 months, four-point scales were used to analyse patients'
      satisfaction and aesthetic outcome. During the study period, 156 patients
      underwent breast reconstruction with 174 DIEP flaps. Fourteen patients (8.9%) had
      breast reconstruction with 19 DIEP flaps and 18 implants. The mean follow-up was
      20.6 months (range 12-32 months). Fourteen implants were placed primarily at the
      time of DIEP reconstruction. The average implant weight was 167.2g with range
      between 100 and 230 g. Implant/flap weight ratio is about 1:5 corresponding to
      20%. In six flaps, the patients had RT before the reconstruction, whilst in three
      cases of delayed DIEP flap augmentation the patients had RT after the DIEP post
      mastectomy reconstruction. One infection and one haematoma, both followed by flap
      partial necrosis, occurred. After 12 months following the completion of
      reconstruction, aesthetic scores were all between good and excellent. Surgical
      indications and outcomes available from this series demonstrate that primary and
      delayed DIEP/implant augmentation can be a safe and effective option in
      optimising breast reconstruction with autologous tissue.

PMID- 18617455
TI  - Does Pubmed accurately reflect the content of major plastic surgery journals?

PMID- 18617456
TI  - Re: 'How to get out of a sticky situation'.

PMID- 18617457
TI  - [Non-alcoholic fatty liver disease and cardiovascular risk].
AB  - Non-alcoholic fatty liver disease is present in 15-25% of the general population.
      The fundamental derangement in non-alcoholic fatty liver disease is insulin
      resistance, a key component of the metabolic syndrome, which includes type 2
      diabetes mellitus, dyslipidemia, hypertension, and obesity. The natural history
      of non-alcoholic fatty liver disease is not always benign, and causality for
      chronic liver disease and cirrhosis is well known in clinical practice and
      sometimes it is accompanied by hepatocellular carcinoma. Non-alcoholic fatty
      liver disease is likely to be associated with increased cardiovascular disease
      risk, and it raises the possibility that non-alcoholic fatty liver disease may be
      not only a marker but also an early mediator of atherosclerosis. Therapy is
      currently directed at treating components of the metabolic syndrome which may be
      beneficial also for the liver.

PMID- 18617458
TI  - [Differential diagnosis of chest pain: point of view of a cardiologist and a
      rheumatologist].
AB  - The rapid development of therapy necessitates early diagnosis in all clinical
      spheres because the attainable result of the therapy depends on this. It is
      especially true in the case of cardial and cerebrovascular events. AIM: Since
      events in the thoracic cavity--life threatening or not--cause pain, the authors,
      based on their own experience and on the literature, present a summary of the
      various differential diagnoses of chest pain. METHOD: The authors discuss the
      causes of chest pain, grouping them according to their risk, frequency and
      topography. CONCLUSION: Even in possession of modern and heavy-duty diagnostical
      and therapeutical possibilities, it is not indispensable, what is more, it is
      necessary to analyse chest pain as a symptom in detail, with the aim of reaching
      the most favourable benefit/risk and benefit/cost ratio, respectively.

PMID- 18617459
TI  - [How do social-economic differences in residential characteristics affect
      mortality? A literature review].
AB  - Authors review studies on associations between mortality and geographic
      distribution of social-economic health determinants published in the last 15
      years. Hungarian publications after the 1990ies identified several indicators
      with effect on mortality related to the place of residence such as size of the
      settlement, population density, joblessness, average income, education, and
      racial or ethnic mixture. As a rule, these papers analyzed time and
      geographically aggregated data with simple descriptive statistical approach.
      Major international studies, however, aside the area indicators commonly included
      individual data and applied multilevel statistical analysis. Earlier, the
      incoherent results of some complex statistical analyses were explained by lack of
      overall health concept, which could utilize effects both at individual and
      population levels. The most recent multilevel statistical methodology, using
      information related to spatial correlation and fitted to health models, can help
      researchers to better understand the causes and effects of health inequities.

PMID- 18617460
TI  - [Vascular endothelial dysfunction, oxidative stress--a new topic within the
      referral section of Orvosi Hetilap].
AB  - The author describes some of the numerous domains regarding the new topic called
      "Vascular endothelial dysfunction, oxidative stress". The endothelium is
      responsible for the constancy and integrity of the milieu interieur by producing
      various substances. Endothelial dysfunction occurs when there is imbalance
      between vasodilators and vasoconstrictors, growth factors and their inhibitors,
      proinflammatory and antiinflammatory agents, prothrombotic and fibrinolytic
      activities. The reason for this imbalance may be response to vascular endothelial
      or intimal injury caused by mechanical, physical, chemical, microbiological,
      immunologic, genetic damage or any of their combination. Endothelial dysfunction
      occurring on the huge inner surface of the vessels (the endothelium) is
      responsible for the triggering of atherosclerosis, which is a chronic vascular
      disease. All the risk factors of vascular pathology are leading to chronic
      (cardio)vascular diseases by causing endothelial dysfunction. Decreased
      endogenous antioxidative capacity leads to oxidative stress by free radical
      reactions of physiological oxidative metabolic processes, ending as the ultimate
      reason for endothelial dysfunction induced by risk factors. The therapeutic and
      preventive effects of causal antioxidant treatments having intracellular and
      mitochondrial effects (statins, angiotensin-converting-enzyme inhibitors,
      angiotensin-receptor-blockers, acetylsalicylic acid, and third generation beta
      blockers) should be emphasized. It is also important to underline the
      physiological-pathophysiological-therapeutic consubstantiality and systemic
      nature of human vasculature and to emphasize the preventive-therapeutic
      significance of the vascular consequence cascade. And finally, there has been
      large process in the assessment of oxidative stress and consecutive endothelial
      dysfunction which revolutionized our clinical point of view.

PMID- 18617461
TI  - [The 43rd Annual Meeting of the European Association for the Study of the Liver
      (EASL), Milan, Italy, April 23-27, 2008].

PMID- 18617463
TI  - [History of a preface--correspondence with Albert Szent-Gyorgyi].

PMID- 18617466
TI  - [Etiology, diagnostics and therapy of hyponatremias].
AB  - Etiopathogenesis, diagnostics and therapy of hyponatremias are summarized for
      clinicians. Hyponatremia is the most common electrolyte abnormality. Mild to
      moderate hyponatremia and severe hyponatremia are found in 15-30% and 1-4% of
      hospitalized patients, respectively. Pathophysiologically, hyponatremias are
      classified into two groups: hyponatremia due to non-osmotic hypersecretion of
      vasopressin (hypovolemic, hypervolemic, euvolemic) and hyponatremia of non
      hypervasopressinemic origin (pseudohyponatremia, water intoxication, cerebral
      salt wasting syndrome). Patients with mild hyponatremia are almost always
      asymptomatic. Severe hyponatremia is usually associated with central nervous
      system symptoms and can be life-threatening. Diagnostic evaluation of patients
      with hyponatremia is directed toward identifying the extracellular fluid volume
      status, the neurological symptoms and signs, the severity and duration of
      hyponatremia, the rate at which hyponatremia developed. The first step to
      determine the probable cause of hyponatremia is the differentiation of the
      hypervasopressinemic and non-hypervasopressinemic hyponatremias with measurement
      of plasma osmolality, glucose, lipids and proteins. For further differential
      diagnosis of hyponatremia, the determination of urine osmolality, the clinical
      assessment of extracellular fluid volume status and the measurement of urine
      sodium concentration provide important information. The most important
      representative of euvolemic hyponatremias is SIADH. The diagnosis of SIADH is
      based on the exclusion of other hyponatremic conditions; low plasma osmolality
      (<275 mosmol/kg) and inappropriate urine concentration (urine osmolality >100
      mosmol/kg) are of pathognomic value. Acute (<48 hrs) severe hyponatremia (<120
      mmol/l) necessitates emergency care with rapid restoration of normal osmotic
      milieu (1 mmol/l/hr increase rate of serum sodium). Patients with chronic
      symptomatic hyponatremia have a high risk of osmotic demyelination syndrome in
      brain if rapid correction of the plasma sodium occurs (maximal rate of correction
      of serum sodium should be 0.5 mmol/l/hr or less). The conventional treatments for
      chronic asymptomatic hyponatremia (except hypovolemic patients) include water
      restriction and/or the use of demeclocycline or lithium or furosemide and salt
      supplementation. Vasopressin receptor antagonists have opened a new forthcoming
      therapeutic era. V2 receptor antagonists, such as lixivaptan, tolvaptan,
      satavaptan and the V2+V1A receptor antagonist conivaptan promote the electrolyte
      sparing excretion of free water and lead to increased serum sodium.

PMID- 18617467
TI  - [The pulmonological manifestations of rheumatoid arthritis].
AB  - In their review article the authors overview the primary and secondary pulmonary
      complications of rheumatoid arthritis with the help of bibliographic data. They
      emphasize the pulmonological complications of disease modifying antirheumatic
      drugs used for the pharmaceutical therapy of rheumatoid arthritis, of which they
      discuss the methotrexate induced pulmonary diseases. Methotrexate participates
      nearly in all of additive double and triple--O'Dell-scheme--combined disease
      modifying antirheumatic drugs therapy. Because of that, the early detection of
      drug-induced pulmonological complications is important. For rheumatologists the
      treatment of methotrexate resistant rheumatoid arthritis is always getting a
      higher and higher challenge. Biological therapeutical drugs act as cytokine
      antagonists, by blocking TNF-alpha and, compared to disease modifying
      antirheumatic drugs, they can more effectively inhibit the progression of the
      disease. These are the biological response modifiers. Their main representatives
      are infliximab, adalimumab, and etanercept. At the end, the authors discuss
      secondary pulmonary complications caused by biological response modifiers, e.g.
      the biological response modifiers associated pulmonary tuberculosis, bacterial
      tracheobronchitis, bacterial pneumonia, bronchiectasia, pulmonary oedema, rapid
      fibrosing alveolitis, and coccidioidomycosis. At 3% of patients with rheumatoid
      arthritis, treated with biological response modifiers, who live in Arizona,
      California, Nevada, pulmonary and systemic mycosis--coccidioidomycosis can appear
      with a 15% of mortality. As a consequence of frequent earthquakes, the spores
      getting into the air from the ground infect immunosuppressed patients treated
      with biological response modifiers. The authors draw attention to the fact that
      patients who receive biological therapy and travel to the above-mentioned endemic
      or earthquake-active regions, have a potential high risk, so it is indispensable
      that they are informed by the doctor. Testing and use of newer and newer groups
      of biological response modifiers are expected in the near future in the therapy
      of rheumatoid arthritis. Nowadays--in patients, who are non-reactive for TNF
      alpha inhibitor treatment--the use of B-lymphocyte inhibitor rituximab,
      characteristic in non-Hodgkin lymphoma therapy is possible. The pulmonary
      complications of rheumatoid arthritis therapy of that cytokine are not known yet.
      Today, antirheumatic therapy results in a significant improvement of patients'
      life-quality, whilst the more and more modern therapeutical methods cause more
      complications.

PMID- 18617468
TI  - [Amyloidosis and the digestive tract].
AB  - Amyloidosis is one of the unusual diseases which may still be underdiagnosed when
      it is affecting the patient. During the last three decades, an enormous progress
      has been made in understanding and improvement of the biochemical nature,
      classification, pathogenesis, clinical features, diagnostic measures and rational
      therapy of this disorder. The varied clinical presentation of gastrointestinal
      amyloidosis makes the diagnosis challenging. It should be considered in patients
      older than 30 years with otherwise unexplained diarrhoea, weight loss, motility
      dysfunction or malabsorption.

PMID- 18617469
TI  - [Wiskott-Aldrich syndrome].
AB  - The Wiskott-Aldrich syndrome is a rare X-linked recessive immunodeficiency
      disorder characterized by thrombocytopenia and small-sized platelets, eczema and
      recurrent infections. This paper describes molecular pathology, diagnostics and
      therapy of the syndrome.

PMID- 18617470
TI  - [mRNA expression analysis and classification of colonic biopsy samples using
      oligonucleotide and cDNA microarray techniques].
AB  - Despite tremendous progress in the past few decades, certain important aspects
      regarding the diagnosis, therapy, and follow-up of colorectal cancer still remain
      unsolved. In our work we searched for biomarkers of the development of colorectal
      carcinoma, and performed gene expression analysis for colorectal disease
      classification. We have established that the oligonucleotide microarray analyses
      of biopsy samples wholly fulfil the Affymetrix quality requirements, are highly
      standard and reproducible and the Taqman microfluidic card system is suitable for
      high-throughput, quick and cost efficient real-time-PCR validation of gene
      expression changes. We have shown that the sequential overexpression of
      osteopontin and osteonectin mRNAs and proteins significantly correlates with the
      progression of the colorectal adenoma-dysplasia-carcinoma sequence. We have
      identified and validated ten novel markers with continuously increasing mRNA
      expression in line with the adenoma-dysplasia-carcinoma transition. We have
      identified the top 27, 13 and 10 genes associated with adenoma, colorectal
      cancer, and inflammatory bowel diseases.

PMID- 18617471
TI  - [Actinomycosis causing acute appendicitis in the puerperium].

PMID- 18617474
TI  - ["The secret of success, how we take advantage of unexpected possibilities."
      Interview with Dr. Arnold Denessel].

PMID- 18617475
TI  - Clinical impact of an inter-hospital transfer strategy in patients with ST
      elevation myocardial infarction undergoing primary angioplasty: the Emilia
      Romagna ST-segment elevation acute myocardial infarction network.
AB  - AIMS: This study sought to evaluate the impact of an inter-hospital transfer
      strategy on treatment times and in-hospital and 1 year cardiac mortality of
      patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing
      primary percutaneous intervention (p-PCI) in the Italian region of Emilia
      Romagna, where an efficient region-wide system for reperfusion has been
      established. METHODS AND RESULTS: 3296 patients with STEMI, undergoing on-site p
      PCI (2444 patients) (OS group) or p-PCI after inter-hospital transfer (852
      patients) (T group) between 1 January 2004 and 30 June 2006 in the Italian region
      of Emilia-Romagna, were considered. During the study period, the number of
      patients undergoing p-PCI increased both for patients admitted to interventional
      centres and for those admitted to peripheral hospitals. At the same time, the
      proportion of patients with STEMI initially admitted to peripheral hospitals and
      not transferred and the door-to-balloon time delays of transfer patients
      decreased. In spite of longer door-to-balloon delay in the transfer group [112
      min (86-147) vs. 71 min (46-104)], in-hospital cardiac mortality (OS 7.0 vs. T
      5.4%, P = 0.10) did not significantly differ between the two groups. After
      multivariable adjustment, the transfer strategy was not associated with increased
      risk of in-hospital [odds ratio 0.956; 95% confidence interval (CI) 0.633-1.442]
      and 1 year (hazard ratio 0.817; 95% CI 0.617-1.085) cardiac mortality.
      CONCLUSION: This study, concerning an established STEMI regional network,
      suggests that a strategy of inter-hospital transfer for p-PCI, when supported by
      an organized system of care, may be applied with rapid reperfusion times and
      favourable short- and long-term clinical outcomes.

PMID- 18617476
TI  - The challenge of reducing time to reperfusion in patients with acute ST elevation
      myocardial infarction.

PMID- 18617477
TI  - Plasma levels of thromboxane A2 on admission are associated with no-reflow after
      primary percutaneous coronary intervention.
AB  - AIMS: Thromboxane A2 (TXA2) is a key mediator of platelet activation and
      aggregation, and an important mediator of platelet-induced coronary artery
      constriction. We sought to investigate whether baseline plasma levels of TXA2 are
      associated with coronary no-reflow after primary percutaneous coronary
      intervention (PPCI). METHODS AND RESULTS: A total of 47 consecutive patients
      (age, 62.5 +/- 12.7; male sex, 76.6%) admitted to our hospital for a first ST
      segment elevation myocardial infarction and undergoing PPCI within 12 h of onset
      of symptoms were enrolled. Admission TXA2 plasma levels were measured by enzyme
      linked immunosorbent assay (ELISA). Angiographic no-reflow was defined as a final
      TIMI flow of <or=2 or final TIMI flow of 3 with a myocardial blush grade of <2,
      whereas ST-segment resolution from baseline value of <or=50% was used as ECG
      index of no-reflow. At multivariable analysis TXA2 plasma levels, endothelin-1
      (ET-1) plasma levels, and left anterior descending coronary artery (LAD) as
      culprit vessel were significant predictors of angiographic no-reflow (P = 0.04),
      whereas TXA2 and ET-1 plasma levels were the only independent predictors of lack
      of ST-segment resolution (P = 0.013 and 0.04, respectively). Of note, TXA2
      tertiles were independent predictors of both angiographic no-reflow and lack of
      ST-segment resolution (OR, 3.5; 95% CI, 1.1-11; P = 0.03 and OR, 3; 95% CI, 1.3
      7; P = 0.01, respectively). CONCLUSION: TXA2 is an independent indicator of no
      reflow that occurs after PPCI. This observation may open new therapeutic
      opportunity in the setting of PPCI.

PMID- 18617478
TI  - No-reflow: the next challenge in treatment of ST-elevation acute myocardial
      infarction.

PMID- 18617479
TI  - The optimal threshold of high post-treatment platelet reactivity could be defined
      by a point-of-care VerifyNow P2Y12 assay.

PMID- 18617480
TI  - A threshold of platelet reactivity for ischaemic events?

PMID- 18617481
TI  - The Ser96Ala variant in histidine-rich calcium-binding protein is associated with
      life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.
AB  - AIMS: To investigate whether genetic variants of the histidine-rich calcium (HRC)
      binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and
      its progression. METHODS AND RESULTS: We screened 123 idiopathic DCM patients and
      96 healthy individuals by single-strand conformation polymorphism analysis and
      direct sequencing for genetic variants in HRC. Six polymorphisms were detected:
      Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (-/GAG),
      Asp261del (GAT/-), and an in-frame insertion of 51 amino acids at His321. The
      analysis of their frequencies did not reveal any significant correlation with DCM
      development. However, the Ser96Ala polymorphism exhibited a statistically
      significant correlation with the occurrence of life-threatening ventricular
      arrhythmias. During a follow-up of 4.02 +/- 2.4 years, the risk for ventricular
      arrhythmias was higher (HR, 9.620; 95% CI, 2.183-42.394; P = 0.003) in the
      Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox
      regression analysis, the Ser96Ala polymorphism was the only significant genetic
      arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838-20.967; P =
      0.018). CONCLUSION: The Ser96Ala genetic variant of HRC is associated with life
      threatening ventricular arrhythmias in idiopathic DCM and may serve as an
      independent predictor of susceptibility to arrhythmogenesis in the setting of
      DCM.

PMID- 18617482
TI  - Acute viral myocarditis.
AB  - Acute myocarditis is one of the most challenging diagnosis in cardiology. At
      present, no diagnostic gold standard is generally accepted, due to the
      insensitivity of traditional diagnostic tests. This leads to the need for new
      diagnostic approaches, which resulted in the emergence of new molecular tests and
      a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent
      findings using these new diagnostic tests resulted in increased interest in
      inflammatory cardiomyopathies and a better understanding of its pathophysiology,
      the recognition in overlap of virus-mediated damage, inflammation, and autoimmune
      dysregulation. Novel results also pointed towards a broader spectrum of viral
      genomes responsible for acute myocarditis, indicating a shift of enterovirus and
      adenovirus to parvovirus B19 and human herpes virus 6. The present review
      proposes a general diagnostic approach, focuses on the viral aetiology and
      associated autoimmune processes, and reviews treatment options for patients with
      acute viral myocarditis.

PMID- 18617483
TI  - Change in N-terminal-pro-B-type-natriuretic-peptide and the risk of sudden death,
      stroke, myocardial infarction, and all-cause mortality in diabetic dialysis
      patients.
AB  - AIMS: N-terminal-pro-B-type-natriuretic-peptide (NT-pro-BNP) concentrations are
      altered in renal failure. This study examined the effect of baseline and change
      from baseline NT-pro-BNP on cardiovascular outcome and mortality in haemodialysis
      patients. METHODS AND RESULTS: On the basis of the German Diabetes and Dialysis
      Study, which evaluated atorvastatin in 1255 type 2 diabetes mellitus (T2DM)
      haemodialysis patients (median follow-up 4 years), the impact of NT-pro-BNP on
      pre-specified, adjudicated endpoints was investigated: sudden death (SD; n =
      160), stroke (n = 99), myocardial infarction (MI; n = 200), cardiovascular events
      (CVEs: cardiac death, MI, stroke; n = 465), all-cause mortality (n = 612).
      Patients with baseline NT-pro-BNP >= 9252 pg/mL (fourth quartile) exhibited a
      more than four-fold risk of stroke [hazard ratio (HR) 4.1; 95% confidence
      interval (CI) 2.0-8.4] and a more than two-fold risk of SD (HR 2.0; 95% CI 1.2
      3.3), CVE (HR 2.0; 95% CI 1.5-2.7), and mortality (HR 2.1; 95% CI 1.6-2.7)
      compared with patients with baseline NT-pro-BNP <= 1433 pg/mL (first quartile).
      Change in NT-pro-BNP was strongly associated with SD, CVE, and mortality.
      Doubling of NT-pro-BNP increased the risk of death by 46% (95% CI 1.1-2.0).
      Neither baseline nor change in NT-pro-BNP was significantly associated with MI.
      CONCLUSION: Increasing NT-pro-BNP is a risk factor for SD, CVE, and mortality in
      haemodialysis patients with T2DM. Whether NT-pro-BNP-guided treatment improves
      outcome needs to be evaluated prospectively.

PMID- 18617484
TI  - Radial artery catheterization and radiological exposure.

PMID- 18617486
TI  - Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults
      being treated for tuberculosis: randomised clinical trial.
AB  - OBJECTIVE: To assess the impact of prophylactic oral co-trimoxazole in reducing
      mortality in HIV positive Zambian adults being treated for pulmonary
      tuberculosis. DESIGN: Double blind placebo controlled randomised clinical trial.
      PARTICIPANTS: Two groups of antiretroviral treatment naive adults with HIV
      infection: patients newly diagnosed as having tuberculosis and receiving
      tuberculosis treatment either for the first time or for retreatment after
      relapse; previously treated patients not receiving treatment. INTERVENTION: Oral
      co-trimoxazole or matching placebo daily. Primary outcome measures Time to death
      and occurrence of serious adverse events related to study drug. RESULTS: 1003
      patients were randomised: 835 (416 co-trimoxazole, 419 placebo) were receiving
      treatment for tuberculosis, 762 (376 co-trimoxazole, 386 placebo) of them newly
      diagnosed previously untreated patients and 73 (40 co-trimoxazole, 33 placebo)
      receiving a retreatment regimen; 168 (84 co-trimoxazole, 84 placebo) were not on
      treatment but had received treatment in the past. Of 835 participants receiving
      tuberculosis treatment, follow-up information was available for 757, with a total
      of 1012.6 person years of follow-up. A total of 310 (147 co-trimoxazole, 163
      placebo) participants died, corresponding to death rates of 27.3 and 34.4 per 100
      person years. In the Cox regression analysis, the hazard ratio for death (co
      trimoxazole:placebo) was 0.79 (95% confidence interval 0.63 to 0.99). The effect
      of co-trimoxazole waned with time, possibly owing to falling adherence levels; in
      a per protocol analysis based on patients who spent at least 90% of their time at
      risk supplied with study drug, the hazard ratio was 0.65 (0.45 to 0.93).
      CONCLUSIONS: Prophylaxis with co-trimoxazole reduces mortality in HIV infected
      adults with pulmonary tuberculosis. Co-trimoxazole was generally safe and well
      tolerated. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15281875.

PMID- 18617487
TI  - Public perception of overweight.

PMID- 18617485
TI  - How frequent is chronic multiyear delusional activity and recovery in
      schizophrenia: a 20-year multi-follow-up.
AB  - To determine how frequent chronic multiyear delusional activity is in modern-day
      schizophrenia, we studied 200 patients over a 20-year period. We also studied the
      relation of delusions to hallucinations and thought disorder-disorganization, to
      work disability, and to later periods of global recovery and assessed several
      protective factors against delusional activity. The sample was assessed 6 times
      over 20 years and includes 43 patients with schizophrenia. Participants were
      evaluated at each follow-up for delusions, hallucinations, thought disorder
      disorganization, work disability, and global recovery. Possible protective
      factors were assessed prospectively at index hospitalization. Twenty-six percent
      of the patients with schizophrenia were delusional at all follow-ups over the 20
      years. Overall, 57% had frequently recurring or persistent delusions. A subgroup
      of over 25% of the schizophrenia patients had no delusional activity at any of
      the 6 follow-ups over 20 years. Schizophrenia patients with posthospital
      delusional activity had increased work disability (P < .05). Delusions that
      persisted after the acute phase in schizophrenia patients predicted a lower
      likelihood of future global recovery (P < .01). In conclusion, slightly over half
      of modern-day schizophrenia patients are vulnerable to frequent or "chronic"
      delusional activity after the acute phase. Schizophreniform patients and other
      types of psychotic disorders are vulnerable to posthospital delusional activity,
      but less frequently, less severely, and more episodically. Delusional activity is
      associated with work disability. Internal factors such as good premorbid
      developmental achievements and favorable prognostic factors are protective
      factors that reduce the probability of chronic multiyear, delusional activity in
      schizophrenia (P < .01).

PMID- 18617488
TI  - Changing perceptions of weight in Great Britain: comparison of two population
      surveys.
AB  - OBJECTIVES: To examine changes in public perceptions of overweight in Great
      Britain over an eight year period. DESIGN: Comparison of data on self perceived
      weight from population surveys in 1999 and 2007. SETTING: Household surveys of
      two representative samples in Great Britain. PARTICIPANTS: 853 men and 944 women
      in 1999, and 847 men and 989 women in 2007. MAIN OUTCOME MEASURES: Participants
      were asked to report their weight and height and classify their body size on a
      scale from "very underweight" to "obese." RESULTS: Self reported weights
      increased dramatically over time, but the weight at which people perceived
      themselves to be overweight also rose significantly. In 1999, 81% of overweight
      participants correctly identified themselves as overweight compared with 75% in
      2007, demonstrating a decrease in sensitivity in the self diagnosis of
      overweight. CONCLUSIONS: Despite media and health campaigns aiming to raise
      awareness of healthy weight, increasing numbers of overweight people fail to
      recognise that their weight is a cause for concern. This makes it less likely
      that they will see calls for weight control as personally relevant.

PMID- 18617489
TI  - Prostate cancer patients with BRCA2 mutation face poor survival.

PMID- 18617490
TI  - Mental health of prisoners is public health problem, says former chief inspector.

PMID- 18617491
TI  - Increasing communication between parents and their children about sex.

PMID- 18617492
TI  - Evaluation of Talking Parents, Healthy Teens, a new worksite based parenting
      programme to promote parent-adolescent communication about sexual health:
      randomised controlled trial.
AB  - OBJECTIVE: To evaluate a worksite based parenting programme-Talking Parents,
      Healthy Teens-designed to help parents learn to address sexual health with their
      adolescent children. DESIGN: Randomised controlled trial (April 2002-December
      2005). SETTING: 13 worksites in southern California. PARTICIPANTS: 569 parents
      completed baseline surveys at work, gave permission for confidential surveys to
      be posted to their adolescent children, and were randomised to intervention or
      control groups. Parents and adolescents completed follow-up surveys at one week,
      three months, and nine months after the programme. INTERVENTION: Talking Parents,
      Healthy Teens consists of eight weekly one hour sessions at worksites for parents
      of adolescent children in 6th-10th grade (about ages 11-16 years). MAIN OUTCOME
      MEASURES: Parent-adolescent communication about a list of sexual topics; whether
      parent taught adolescent how to use a condom; ability to communicate with
      parent/adolescent about sex; openness of parent-adolescent communication about
      sex. RESULTS: Differences between intervention and control groups were
      significant for the mean number of new sexual topics that parents and adolescents
      reported discussing between baseline and each follow-up (P<0.001 for each);
      intervention parents were less likely than controls to discuss no new topics (8%
      v 29%, 95% confidence interval for difference 16% to 24%) and more likely to
      discuss seven or more new topics (38% v 8%, 19% to 41%) at nine months. Some
      differences increased after completion of the programme: at one week after the
      programme, 18% of adolescents in the intervention group and 3% in the control
      group (6% to 30%) said that their parents had reviewed how to use a condom since
      baseline (P<0.001); this grew to 29% v 5% (13% to 36%) at nine months (P<0.001).
      Compared with controls at nine months, parents and adolescents in the
      intervention group reported greater ability to communicate with each other about
      sex (P<0.001) and more openness in communication about sex (P<0.001).
      CONCLUSIONS: A worksite based programme can have substantial effects on
      communication between parents and adolescents about sexual health. TRIAL
      REGISTRATION: Clinical Trials NCT00465010.

PMID- 18617493
TI  - Gallbladder disease and use of transdermal versus oral hormone replacement
      therapy in postmenopausal women: prospective cohort study.
AB  - OBJECTIVE: To determine whether transdermal compared with oral use of hormone
      replacement therapy reduces the risk of gallbladder disease in postmenopausal
      women. DESIGN: Prospective cohort study (Million Women Study). SETTING: Women
      registered with the National Health Service (NHS) in England and Scotland.
      PARTICIPANTS: 1,001,391 postmenopausal women (mean age 56) recruited between 1996
      and 2001 from NHS breast screening centres and followed by record linkage to
      routinely collected NHS hospital admission data for gallbladder disease. MAIN
      OUTCOME MEASURES: Adjusted relative risk and standardised incidence rates of
      hospital admission for gallbladder disease or cholecystectomy according to use of
      hormone replacement therapy. RESULTS: During follow-up 19 889 women were admitted
      for gallbladder disease; 17 190 (86%) had a cholecystectomy. Compared with never
      users of hormone replacement therapy, current users were more likely to be
      admitted for gallbladder disease (relative risk 1.64, 95% confidence interval
      1.58 to 1.69) but risks were substantially lower with transdermal therapy than
      with oral therapy (relative risk 1.17, 1.10 to 1.24 v 1.74, 1.68 to 1.80;
      heterogeneity P<0.001). Among women using oral therapy, equine oestrogens were
      associated with a slightly greater risk of gallbladder disease than estradiol
      (relative risk 1.79, 1.72 to 1.87 v 1.62, 1.54 to 1.70; heterogeneity P<0.001)
      and higher doses of oestrogen increased the risk more than lower doses: for
      equine oestrogens >0.625 mg, 1.91 (1.78 to 2.04) v <or=0.625 mg, 1.76 (1.68 to
      1.84); heterogeneity P=0.02; estradiol >1 mg, 1.68 (1.59 to 1.77) v <or=1 mg,
      1.44 (1.31 to 1.59); heterogeneity P=0.003. The risk of gallbladder disease
      decreased with time since stopping therapy (trend P=0.004). Results were similar
      taking cholecystectomy as the outcome. Standardised hospital admission rates per
      100 women over five years for cholecystectomy were 1.1 in never users, 1.3 with
      transdermal therapy, and 2.0 with oral therapy. CONCLUSION: Gallbladder disease
      is common in postmenopausal women and use of hormone replacement therapy
      increases the risk. Use of transdermal therapy rather than oral therapy over a
      five year period could avoid one cholecystectomy in every 140 users.

PMID- 18617494
TI  - Health costs of recycling.

PMID- 18617495
TI  - Evidence of support for biobanking practices.

PMID- 18617496
TI  - Patients' refusal to consent to storage and use of samples in Swedish biobanks:
      cross sectional study.
AB  - OBJECTIVES: To estimate how many people object to storage of biological samples
      collected in health care in Sweden and to their use in research and how many
      withdraw previous consent. DESIGN: Cross sectional study of register data.
      SETTING: Biobanks used in Swedish health care, 2005-6. Population Data on refusal
      to consent were obtained for 1.4 million biobank samples per year from 20 of 21
      counties. MAIN OUTCOME MEASURES: Rates of preliminary refusal to consent,
      confirmed refusal, and withdrawal of consent. RESULTS: Patients refused consent
      to either storage or use of their samples in about 1 in 690 cases; about 1 in
      1600 confirmed their decision by completing a dissent form. Rather than having
      the samples destroyed, about 1 in 6200 patients wanted to restrict their use. Of
      those who had previously consented, about 1 in 19,000 withdrew their consent.
      CONCLUSIONS: Refusal to consent to biobank research in Sweden is rare, and the
      interests of individuals and research interests need not be at odds. The Swedish
      healthcare organisation is currently obliged to obtain either consent or refusal
      to each potential use of each sample taken, and lack of consent to research is
      used as the default position. A system of presumed consent with straightforward
      opt out would correspond with people's attitudes, as expressed in their actions,
      towards biobank research.

PMID- 18617497
TI  - Omeprazole and refractory hypomagnesaemia.

PMID- 18617498
TI  - Fungal nail infection.

PMID- 18617499
TI  - MPs table amendments to make it easier to obtain early abortions.

PMID- 18617500
TI  - Staffing and poor team work are letting maternity services down, says report.

PMID- 18617502
TI  - Government's obesity strategy targets parents of children under 10.

PMID- 18617503
TI  - Influence of different brazing and welding methods on tensile strength and
      microhardness of orthodontic stainless steel wire.
AB  - The aim of this study was to compare the mechanical strength and microhardness of
      joints made by conventional brazing and tungsten inert gas (TIG) and laser
      welding. A standardized end-to-end joint configuration of the orthodontic wire
      material in spring hard quality was used. The joints were made using five
      different methods: brazing (soldering > 450 degrees C) with universal silver
      solder, two TIG, and two laser welders. Laser parameters and welding conditions
      were used according to the manufacturers' guidance. The tensile strengths were
      measured with a universal testing machine (Zwick 005). The microhardness
      measurements were carried out with a hardness tester (Zwick 3202). Data were
      analysed using one-way analysis of variance and Bonferroni's post hoc correction
      (P < 0.05). In all cases, brazing joints ruptured at low levels of tensile
      strength (198 +/- 146 MPa). Significant differences (P < 0.001) between brazing
      and TIG or laser welding were found. The highest means were observed for TIG
      welding (699-754 MPa). Laser welding showed a significantly lower mean tensile
      strength (369-520 MPa) compared with TIG welding. Significant differences (P <
      0.001) were found between the original orthodontic wire and the mean
      microhardness at the centre of the welded area. The mean microhardness differed
      significantly between brazing (1.99 GPa), TIG (2.22-2.39 GPa) and laser welding
      (2.21-2.68 GPa). For orthodontic purposes, laser and TIG welding are solder-free
      alternatives to joining metal. TIG welding with a lower investment cost is
      comparable with laser welding. However, while expensive, the laser technique is a
      sophisticated and simple method.

PMID- 18617504
TI  - Genetic and molecular characterization of three novel S-haplotypes in sour cherry
      (Prunus cerasus L.).
AB  - Tetraploid sour cherry (Prunus cerasus L.) exhibits gametophytic self
      incompatibility (GSI) whereby the specificity of self-pollen rejection is
      controlled by alleles of the stylar and pollen specificity genes, S-RNase and SFB
      (S haplotype-specific F-box protein gene), respectively. As sour cherry
      selections can be either self-compatible (SC) or self-incompatible (SI),
      polyploidy per se does not result in SC. Instead the genotype-dependent loss of
      SI in sour cherry is due to the accumulation of non-functional S-haplotypes. The
      presence of two or more non-functional S-haplotypes within sour cherry 2x pollen
      renders that pollen SC. Two new S-haplotypes from sour cherry, S(33) and S(34),
      that are presumed to be contributed by the P. fruticosa species parent, the
      complete S-RNase and SFB sequences of a third S-haplotype, S(35), plus the
      presence of two previously identified sweet cherry S-haplotypes, S(14) and S(16)
      are described here. Genetic segregation data demonstrated that the S(16)-, S(33)
      , S(34)-, and S(35)-haplotypes present in sour cherry are fully functional. This
      result is consistent with our previous finding that 'hetero-allelic' pollen is
      incompatible in sour cherry. Phylogenetic analyses of the SFB and S-RNase
      sequences from available Prunus species reveal that the relationships among S
      haplotypes show no correspondence to known organismal relationships at any
      taxonomic level within Prunus, indicating that polymorphisms at the S-locus have
      been maintained throughout the evolution of the genus. Furthermore, the
      phylogenetic relationships among SFB sequences are generally incongruent with
      those among S-RNase sequences for the same S-haplotypes. Hypotheses compatible
      with these results are discussed.

PMID- 18617505
TI  - A xylem sap retrieval pathway in rice leaf blades: evidence of a role for
      endocytosis?
AB  - The structure and transport properties of pit membranes at the interface between
      the metaxylem and xylem parenchyma cells and the possible role of these pit
      membranes in solute transfer to the phloem were investigated. Electron microscopy
      revealed a fibrillar, almost tubular matrix within the pit membrane structure
      between the xylem vessels and xylem parenchyma of leaf blade bundles in rice
      (Oryza sativa). These pits are involved primarily with regulating water flux to
      the surrounding xylem parenchyma cells. Vascular parenchyma cells contain large
      mitochondrial populations, numerous dictyosomes, endomembrane complexes, and
      vesicles in close proximity to the pit membrane. Taken collectively, this
      suggests that endocytosis may occur at this interface. A weak solution of 5,6
      carboxyfluorescein diacetate (5,6-CFDA) was applied to cut ends of leaves and,
      after a minimum of 30 min, the distribution of the fluorescent cleavage product,
      5,6-carboxyfluorescein (5,6-CF), was observed using confocal microscopy. Cleavage
      of 5,6-CFDA occurred within the xylem parenchyma cells, and the non-polar 5,6-CF
      was then symplasmically transported to other parenchyma elements and ultimately,
      via numerous pore plasmodesmata, to adjacent thick-walled sieve tubes.
      Application of Lucifer Yellow, and, separately, Texas Red-labelled dextran (10
      kDa) to the transpiration stream, confirmed that these membrane-impermeant probes
      could only have been offloaded from the xylem via the xylem vessel-xylem
      parenchyma pit membranes, suggesting endocytotic transmembrane transfer of these
      membrane-impermeant fluorophores. Accumulation within the thick-walled sieve
      tubes, but not in thin-walled sieve tubes, confirms the presence of a symplasmic
      phloem loading pathway, via pore plasmodesmata between xylem parenchyma and thick
      walled sieve tubes, but not thin-walled sieve tubes.

PMID- 18617506
TI  - Short-long-short sequence caused by ventricular safety pacing inducing
      ventricular tachycardia in a patient with a dual-chamber implantable cardioverter
      defibrillator.
AB  - Ventricular safety pacing (VSP) is an algorithm used to prevent crosstalk
      inhibition and ventricular capture during the vulnerable period. We report a 78
      year-old man with implantable dual-chamber defibrillator, in whom clusters of
      ventricular tachycardias (VTs) were provoked by the VSP. During rapid DDDR
      pacing, the delivery of the VSP after every other atrial-paced beat resulted in
      short-long-short ventricular sequences and induced VTs. An atrial-based lower
      rate timing, long atrioventricular pacing interval, and automatic gain control
      also accounted for this arrhythmogenic ventricular sequence. The VSP and the
      subsequent VT were eliminated by decreasing the pacing rate.

PMID- 18617508
TI  - Identification of structural and functional O-linked N-acetylglucosamine-bearing
      proteins in Xenopus laevis oocyte.
AB  - O-Linked N-acetylglucosaminylation (O-GlcNAcylation) (or O-linked N
      acetylglucosamine (O-GlcNAc)) is an abundant and reversible glycosylation type
      found within the cytosolic and the nuclear compartments. We have described
      previously the sudden O-GlcNAcylation increase occurring during the Xenopus
      laevis oocyte G(2)/M transition, and we have demonstrated that the inhibition of
      O-GlcNAc-transferase (OGT) blocked this process, showing that the O-GlcNAcylation
      dynamism interferes with the cell cycle progression. In this work, we identified
      proteins that are O-GlcNAc-modified during the G(2)/M transition. Because of a
      low expression of O-GlcNAcylation in Xenopus oocyte, classical enrichment of O
      GlcNAc-bearing proteins using O-GlcNAc-directed antibodies or wheat germ
      agglutinin lectin affinity were hard to apply, albeit these techniques allowed
      the identification of actin and erk2. Therefore, another strategy based on an in
      vitro enzymatic labeling of O-GlcNAc residues with azido-GalNAc followed by a
      chemical addition of a biotin alkyne probe and by enrichment of the tagged
      proteins on avidin beads was used. Bound proteins were analyzed by nano-LC-nano
      ESI-MS/MS allowing for the identification of an average of 20 X. laevis oocyte O
      GlcNAcylated proteins. In addition to actin and beta-tubulin, we identified
      metabolic/functional proteins such as PP2A, proliferating cell nuclear antigen,
      transitional endoplasmic reticulum ATPase, aldolase, lactate dehydrogenase, and
      ribosomal proteins. This labeling allowed for the mapping of a major O
      GlcNAcylation site within the 318-324 region of beta-actin. Furthermore
      immunofluorescence microscopy enabled the direct visualization of O-GlcNAcylation
      and OGT on the meiotic spindle as well as the observation that chromosomally
      bound proteins were enriched in O-GlcNAc and OGT. The biological relevance of
      this post-translational modification both on microtubules and on chromosomes
      remains to be determined. However, the mapping of the O-GlcNAcylation sites will
      help to underline the function of this post-translational modification on each
      identified protein and will provide a better understanding of O-GlcNAcylation in
      the control of the cell cycle.

PMID- 18617507
TI  - Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and
      VRK2 (vaccinia-related kinase) activities.
AB  - Human vaccinia-related kinase (VRK) 1 is a novel serine-threonine kinase that
      regulates several transcription factors, nuclear envelope assembly, and chromatin
      condensation and is also required for cell cycle progression. The regulation of
      this kinase family is unknown. Mass spectrometry has permitted the identification
      of Ran as an interacting and regulatory protein of the VRK serine-threonine
      kinase activities. The stable interaction has been validated by pulldown of
      endogenous proteins as well as by reciprocal immunoprecipitations. The three
      members of the VRK family stably interact with Ran, and the interaction was not
      affected by the bound nucleotide, GDP or GTP. The interaction was stronger with
      the RanT24N that is locked in its inactive conformation and cannot bind
      nucleotides. None of the kinases phosphorylated Ran or RCC1. VRK1 does not
      directly interact with RCC1, but if Ran is present they can be isolated as a
      complex. The main effect of the interaction of inactive RanGDP with VRK1 is the
      inhibition of its kinase activity, which was detected by a reduction in VRK1
      autophosphorylation and a reduction in phosphorylation of histone H3 in residues
      Thr-3 and Ser-10. The kinase activity inhibition can be relieved by the
      interaction with the constitutively active RanGTP or RanL43E, which locks Ran in
      its GTP-bound active conformation. In this complex, the interaction with VRK
      proteins does not alter the effect of its guanine exchange factor, RCC1. Ran is a
      novel negative regulator of nuclear VRK1 and VRK2 kinase activity, which may vary
      in different subcellular localizations generating an asymmetric intracellular
      distribution of kinase activity depending on local protein interactions.

PMID- 18617509
TI  - Correlation between case mix index and antibiotic use in hospitals.
AB  - BACKGROUND: To compare the quantitative antibiotic use between hospitals or
      hospital units and to explore differences, adjustment for severity of illness of
      hospitalized patients is essential. The case mix index (CMI) is an economic
      surrogate marker (i.e. the total cost weights of all inpatients per a defined
      time period divided by the number of admissions) to describe the average
      patients' morbidity of individual hospitals. We aimed to investigate the
      correlation between CMI and hospital antibiotic use. METHODS: We used weighted
      linear regression analysis to evaluate the correlation between in-hospital
      antibiotic use in 2006 and CMI of 18 departments of the tertiary care University
      Hospital Zurich and of 10 primary and 2 secondary acute care hospitals in the
      Canton of Zurich in Switzerland. RESULTS: Antibiotic use varied substantially
      between different departments of the university hospital [defined daily doses
      (DDD)/100 bed-days, 68.04; range, 20.97-323.37] and between primary and secondary
      care hospitals (range of DDD/100 bed-days, 15.45-57.05). Antibiotic use of
      university hospital departments and the different hospitals, respectively,
      correlated with CMI when calculated in DDD/100 bed-days [coefficient of
      determination (R(2)), 0.57 (P = 0.0002) and 0.46 (P = 0.0065)], as well as when
      calculated in DDD/100 admissions [R(2), 0.48 (P = 0.0008) and 0.85 (P < 0.0001),
      respectively]. CONCLUSIONS: Antibiotic use correlated with CMI across various
      specialties of a university hospital and across different acute care hospitals.
      For benchmarking antibiotic use within and across hospitals, adjustment for CMI
      may be a useful tool in order to take into account the differences in hospital
      category and patients' morbidities.

PMID- 18617510
TI  - Carbonic anhydrase in the scleractinian coral Stylophora pistillata:
      characterization, localization, and role in biomineralization.
AB  - Carbonic anhydrases (CA) play an important role in biomineralization from
      invertebrates to vertebrates. Previous experiments have investigated the role of
      CA in coral calcification, mainly by pharmacological approaches. This study
      reports the molecular cloning, sequencing, and immunolocalization of a CA
      isolated from the scleractinian coral Stylophora pistillata, named STPCA. Results
      show that STPCA is a secreted form of alpha-CA, which possesses a CA catalytic
      function, similar to the secreted human CAVI. We localized this enzyme at the
      calicoblastic ectoderm level, which is responsible for the precipitation of the
      skeleton. This localization supports the role of STPCA in the calcification
      process. In symbiotic scleractinian corals, calcification is stimulated by light,
      a phenomenon called "light-enhanced calcification" (LEC). The mechanism by which
      symbiont photosynthesis stimulates calcification is still enigmatic. We tested
      the hypothesis that coral genes are differentially expressed under light and dark
      conditions. By real-time PCR, we investigated the differential expression of
      STPCA to determine its role in the LEC phenomenon. Results show that the STPCA
      gene is expressed 2-fold more during the dark than the light. We suggest that in
      the dark, up-regulation of the STPCA gene represents a mechanism to cope with
      night acidosis.

PMID- 18617511
TI  - The P2X7 carboxyl tail is a regulatory module of P2X7 receptor channel activity.
AB  - P2X(7) receptors are ATP-gated cation channels composed of three identical
      subunits, each having intracellular amino and carboxyl termini and two
      transmembrane segments connected by a large ectodomain. Within the P2X family,
      P2X(7) subunits are unique in possessing an extended carboxyl tail. We expressed
      the human P2X(7) subunit as two complementary fragments, a carboxyl tail
      truncated receptor channel core (residues 1-436 or 1-505) and a tail extension
      (residues 434-595) in Xenopus laevis oocytes. P2X(7) channel core subunits
      efficiently assembled as homotrimers that appeared abundantly at the oocyte
      surface, yet produced only approximately 5% of the full-length P2X(7) receptor
      current. Co-assembly of channel core subunits with full-length P2X(7) subunits
      inhibited channel current, indicating that the lack of a single carboxyl tail
      domain is dominant-negative for P2X(7) receptor activity. Co-expression of the
      tail extension as a discrete protein increased ATP-gated current amplitudes of
      P2X(7) channel cores 10-20-fold, fully reconstituting the wild type
      electrophysiological phenotype of the P2X(7) receptor. Chemical cross-linking
      revealed that the discrete tail extension bound with unity stoichiometry to the
      carboxyl tail of the P2X(7) channel core. We conclude that a non-covalent
      association of crucial functional importance exists between the carboxyl tail of
      the channel core and the tail extension. Using a slightly shorter P2X(7) subunit
      core and subfragments of the tail extension, this association could be narrowed
      down to include residues 409-436 and 434-494 of the split receptor. Together,
      these results identify the tail extension as a regulatory gating module,
      potentially making P2X(7) channel gating sensitive to intracellular regulation.

PMID- 18617512
TI  - Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is required for
      interleukin (IL)-1-mediated optimal NFkappaB and AP-1 activation as well as IL-6
      gene expression.
AB  - TAK1 (transforming growth factor-beta-activated kinase 1), a mitogen-activated
      protein kinase kinase kinase, is activated by various cytokines, including
      interleukin-1 (IL-1). However, the precise regulation for TAK1 activation at the
      molecular level is still not fully understood. Here we report that dual
      phosphorylation of Thr-178 and Thr-184 residues within the kinase activation loop
      of TAK1 is essential for TAK1-mediated NFkappaB and AP-1 activation. Once co
      overexpressed with TAB1, TAK1 mutant with alanine substitution of these two
      residues fails to activate IKKbeta-mediated NFkappaB and JNK-mediated AP-1,
      whereas TAK1 mutant with replacement of these two sites with acidic residues acts
      like the TAK1 wild type. Consistently, TAK1 mutant with alanine substitution of
      these two residues severely inhibits IL-1-induced NFkappaB and AP-1 activities,
      whereas TAK1 mutant with replacement of these two sites with acidic residues
      slightly enhances IL-1-induced NFkappaB and AP-1 activities compared with the
      TAK1 wild-type. IL-1 induces the phosphorylation of endogenous TAK1 at Thr-178
      and Thr-184. Reconstitution of TAK1-deficient mouse embryo fibroblast cells with
      wild-type TAK1 or a TAK1 mutant containing threonine 178 and 184 to alanine
      mutations revealed the importance of these two sites in IL-1-mediated IKK
      NFkappaB and JNK-AP-1 activation as well as IL-1-induced IL-6 gene expression.
      Our finding is the first report that substitution of key serine/threonine
      residues with acidic residues mimics the phosphorylated state of TAK1 and renders
      TAK1 active during its induced activation.

PMID- 18617513
TI  - The RING domain and first zinc finger of TRAF6 coordinate signaling by
      interleukin-1, lipopolysaccharide, and RANKL.
AB  - TRAF6, a crucial adaptor molecule in innate and adaptive immunity, contains three
      distinct functional domains. The C-terminal TRAF domain facilitates
      oligomerization and sequence-specific interaction with receptors or other adaptor
      proteins. In conjunction with the dimeric E2 enzyme Ubc13-Uev1A, the N-terminal
      RING domain of TRAF6 functions as an E3 ubiquitin (Ub) ligase that facilitates
      its own site-specific ubiquitination through the generation of a Lys-63-linked
      poly-Ub chain. This modification does not cause its proteasomal degradation but
      rather serves as a scaffold to activate both the IKK and stress kinase pathways.
      Connecting the N-and C-terminal regions, the four internal zinc finger (ZF)
      motifs have yet to be functionally defined. In this study, we examined the role
      of the ZF domains in interleukin-1, lipopolysaccharide, and RANKL signaling by
      reconstitution of TRAF6-deficient cells with point mutations or deletions of
      these ZF motifs. Although ZF domains 2-4 are dispensable for activating IKK, p38,
      and JNK by interleukin-1 and lipopolysaccharide, the first ZF domain together
      with an intact RING domain of TRAF6 is essential for activating these pathways.
      Furthermore, TRAF6 autoubiquitination and its interaction with Ubc13 are
      dependent on ZF1 and an intact RING domain. Additionally, expression of TRAF6
      lacking ZF2-4 in TRAF6-deficient monocytes rescues RANKL-mediated osteoclast
      differentiation and LPS-stimulated interleukin-6 production. These data provide
      evidence for the critical role of the Ub ligase activity of TRAF6, which is
      coordinated via the RING domain and ZF1 to supply the necessary elements in
      signaling by cytokines dependent upon TRAF6.

PMID- 18617514
TI  - Cdt1 and Cdc6 are destabilized by rereplication-induced DNA damage.
AB  - The replication factors Cdt1 and Cdc6 are essential for origin licensing, a
      prerequisite for DNA replication initiation. Mechanisms to ensure that metazoan
      origins initiate once per cell cycle include degradation of Cdt1 during S phase
      and inhibition of Cdt1 by the geminin protein. Geminin depletion or
      overexpression of Cdt1 or Cdc6 in human cells causes rereplication, a form of
      endogenous DNA damage. Rereplication induced by these manipulations is however
      uneven and incomplete, suggesting that one or more mechanisms restrain
      rereplication once it begins. We find that both Cdt1 and Cdc6 are degraded in
      geminin-depleted cells. We further show that Cdt1 degradation in cells that have
      rereplicated requires the PCNA binding site of Cdt1 and the Cul4(DDB1) ubiquitin
      ligase, and Cdt1 can induce its own degradation when overproduced. Cdc6
      degradation in geminin-depleted cells requires Huwe1, the ubiquitin ligase that
      regulates Cdc6 after DNA damage. Moreover, perturbations that specifically
      disrupt Cdt1 and Cdc6 degradation in response to DNA damage exacerbate
      rereplication when combined with geminin depletion, and this enhanced
      rereplication occurs in both human cells and in Drosophila melanogaster cells. We
      conclude that rereplication-associated DNA damage triggers Cdt1 and Cdc6
      ubiquitination and destruction, and propose that this pathway represents an
      evolutionarily conserved mechanism that minimizes the extent of rereplication.

PMID- 18617515
TI  - Demonstration of short-lived complexes of cytochrome c with cytochrome bc1 by EPR
      spectroscopy: implications for the mechanism of interprotein electron transfer.
AB  - One of the steps of a common pathway for biological energy conversion involves
      electron transfer between cytochrome c and cytochrome bc1. To clarify the
      mechanism of this reaction, we examined the structural association of those two
      proteins using the electron transfer-independent electron paramagnetic resonance
      (EPR) techniques. Drawing on the differences in the continuous wave EPR spectra
      and saturation recoveries of spin-labeled bacterial and mitochondrial cytochromes
      c recorded in the absence and presence of bacterial cytochrome bc1, we have
      exposed a time scale of dynamic equilibrium between the bound and the free state
      of cytochrome c at various ionic strengths. Our data show a successive decrease
      of the bound cytochrome c fraction as the ionic strength increases, with a limit
      of approximately 120 mm NaCl above which essentially no bound cytochrome c can be
      detected by EPR. This limit does not apply to all of the interactions of
      cytochrome c with cytochrome bc1 because the cytochrome bc1 enzymatic activity
      remained high over a much wider range of ionic strengths. We concluded that EPR
      monitors just the tightly bound state of the association and that an averaged
      lifetime of this state decreases from over 100 micros at low ionic strength to
      less than 400 ns at an ionic strength above 120 mm. This suggests that at
      physiological ionic strength, the tightly bound complex on average lasts less
      than the time needed for a single electron exchange between hemes c and c1,
      indicating that productive electron transfer requires several collisions of the
      two molecules. This is consistent with an early idea of diffusion-coupled
      reactions that link the soluble electron carriers with the membranous complexes,
      which, we believe, provides a robust means of regulating electron flow through
      these complexes.

PMID- 18617516
TI  - Alpha-actinin-4 is selectively required for insulin-induced GLUT4 translocation.
AB  - Insulin induces GLUT4 translocation to the muscle cell surface. Using
      differential amino acid labeling and mass spectrometry, we observed insulin
      dependent co-precipitation of actinin-4 (ACTN4) with GLUT4 (Foster, L. J.,
      Rudich, A., Talior, I., Patel, N., Huang, X., Furtado, L. M., Bilan, P. J., Mann,
      M., and Klip, A. (2006) J. Proteome Res. 5, 64-75). ACTN4 links F-actin to
      membrane proteins, and actin dynamics are essential for GLUT4 translocation. We
      hypothesized that ACTN4 may contribute to insulin-regulated GLUT4 traffic. In L6
      muscle cells insulin, but not platelet-derived growth factor, increased co
      precipitation of ACTN4 with GLUT4. Small interfering RNA-mediated ACTN4 knockdown
      abolished the gain in surface-exposed GLUT4 elicited by insulin but not by
      platelet-derived growth factor, membrane depolarization, or mitochondrial
      uncoupling. In contrast, knockdown of alpha-actinin-1 (ACTN1) did not prevent
      GLUT4 translocation by insulin. GLUT4 colocalized with ACTN4 along the insulin
      induced cortical actin mesh and ACTN4 knockdown prevented GLUT4-actin
      colocalization without impeding actin remodeling or Akt phosphorylation,
      maintaining GLUT4 in a tight perinuclear location. We propose that ACTN4
      contributes to GLUT4 traffic, likely by tethering GLUT4 vesicles to the cortical
      actin cytoskeleton.

PMID- 18617517
TI  - Ubiquitin-proteasome-mediated degradation of keratin intermediate filaments in
      mechanically stimulated A549 cells.
AB  - We previously reported that shear stress induces phosphorylation and disassembly
      of keratin intermediate filaments (IFs). Shear stress also induces a time- and
      strain-dependent degradation of keratin IFs, and the current study examines the
      mechanisms involved in degradation of keratin proteins in human A549 cells
      exposed to 0-24 h of shear stress (7.5-30 dynes/cm(2)). Ubiquitin was found to be
      covalently associated with keratin proteins immunoprecipitated from shear
      stressed cells, and pretreatment with the proteasomal inhibitor MG132 prevented
      the degradation of the keratin IF network. Importantly, phosphorylation of K8 Ser
      73 is required for the shear stress-mediated ubiquitination, disassembly, and
      degradation of the keratin IF network. Immunofluorescence microscopy revealed
      that shear stress caused the thin array of keratin fibrils observed in control
      cells to be reorganized into a perinuclear aggregate, known as an aggresome, and
      that ubiquitin was also associated with this structure. Finally, the E2 enzymes,
      UbcH5b, -c, and Ubc3, but not E2-25K are required for the shear stress-mediated
      ubiquitin-proteasomal degradation of keratin proteins. These data suggest that
      shear stress promotes the disassembly and degradation of the keratin IF network
      via phosphorylation and the ubiquitin-proteasome pathway.

PMID- 18617518
TI  - Intracellular peptides as natural regulators of cell signaling.
AB  - Protein degradation by the ubiquitin proteasome system releases large amounts of
      oligopeptides within cells. To investigate possible functions for these
      intracellularly generated oligopeptides, we fused them to a cationic
      transactivator peptide sequence using reversible disulfide bonds, introduced them
      into cells, and analyzed their effect on G protein-coupled receptor (GPCR) signal
      transduction. A mixture containing four of these peptides (20-80 microm)
      significantly inhibited the increase in the extracellular acidification response
      triggered by angiotensin II (ang II) in CHO-S cells transfected with the ang II
      type 1 receptor (AT1R-CHO-S). Subsequently, either alone or in a mixture, these
      peptides increased luciferase gene transcription in AT1R CHO-S cells stimulated
      with ang II and in HEK293 cells treated with isoproterenol. These peptides
      without transactivator failed to affect GPCR cellular responses. All four
      functional peptides were shown in vitro to competitively inhibit the degradation
      of a synthetic substrate by thimet oligopeptidase. Overexpression of thimet
      oligopeptidase in both CHO-S and HEK293 cells was sufficient to reduce luciferase
      activation triggered by a specific GPCR agonist. Moreover, using individual
      peptides as baits in affinity columns, several proteins involved in GPCR
      signaling were identified, including alpha-adaptin A and dynamin 1. These results
      suggest that before their complete degradation, intracellular peptides similar to
      those generated by proteasomes can actively affect cell signaling, probably
      representing additional bioactive molecules within cells.

PMID- 18617519
TI  - Rad51 protein stimulates the branch migration activity of Rad54 protein.
AB  - The Rad51 and Rad54 proteins play important roles during homologous recombination
      in eukaryotes. Rad51 forms a nucleoprotein filament on single-stranded DNA and
      performs the initial steps of double strand break repair. Rad54 belongs to the
      Swi2/Snf2 family of ATP-dependent DNA translocases. We previously showed that
      Rad54 promotes branch migration of Holliday junctions. Here we find that human
      Rad51 (hRad51) significantly stimulates the branch migration activity of hRad54.
      The stimulation appears to be evolutionarily conserved, as yeast Rad51 also
      stimulates the branch migration activity of yeast Rad54. We further investigated
      the mechanism of this stimulation. Our results demonstrate that the stimulation
      of hRad54-promoted branch migration by hRad51 is driven by specific protein
      protein interactions, and the active form of the hRad51 filament is more
      stimulatory than the inactive one. The current results support the hypothesis
      that the hRad51 conformation state has a strong effect on interaction with hRad54
      and ultimately on the function of hRad54 in homologous recombination.

PMID- 18617520
TI  - Kruppel-like factor 5 causes cartilage degradation through transactivation of
      matrix metalloproteinase 9.
AB  - Although degradation of cartilage matrix has been suggested to be a rate-limiting
      step for endochondral ossification during skeletal development, little is known
      about the transcriptional regulation. This study investigated the involvement of
      KLF5 (Kruppel-like factor 5), an Sp/KLF family member, in the skeletal
      development. KLF5 was expressed in chondrocytes and osteoblasts but not in
      osteoclasts. The heterozygous deficient (KLF5+/-) mice exhibited skeletal growth
      retardation in the perinatal period. Although chondrocyte proliferation and
      differentiation were normal, cartilage matrix degradation was impaired in KLF5+/-
      mice, causing delay in replacement of cartilage with bone at the primary
      ossification center in the embryonic limbs and elongation of hypertrophic
      chondrocyte layer in the neonatal growth plates. Microarray analyses identified
      MMP9 (matrix metalloproteinase 9) as a transcriptional target, since it was
      strongly up-regulated by adenoviral transfection of KLF5 in chondrogenic cell
      line OUMS27. The KLF5 overexpression caused gelatin degradation by stimulating
      promoter activity of MMP9 without affecting chondrocyte differentiation or
      vascular endothelial growth factor expression in the culture of chondrogenic
      cells; however, in osteoclast precursors, it affected neither MMP9 expression nor
      osteoclastic differentiation. KLF5 dysfunction by genetic heterodeficiency or RNA
      interference was confirmed to cause reduction of MMP9 expression in cultured
      chondrogenic cells. MMP9 expression was decreased in the limbs of KLF5+/-
      embryos, which was correlated with suppression of matrix degradation,
      calcification, and vascularization. We conclude that KLF5 causes cartilage matrix
      degradation through transcriptional induction of MMP9, providing the first
      evidence that transcriptional regulation of a proteinase contributes to
      endochondral ossification and skeletal development.

PMID- 18617521
TI  - Opening and closing of the hydrophobic cavity of LolA coupled to lipoprotein
      binding and release.
AB  - Outer membrane-specific lipoproteins of Escherichia coli are released from the
      inner membrane through the action of Lol-CDE, which leads to the formation of a
      complex between the lipoprotein and LolA, a periplasmic chaperone. LolA then
      transfers lipoproteins to LolB, a receptor in the outer membrane. The structures
      of LolA and LolB are very similar, having an incomplete beta-barrel covered with
      an alpha-helical lid forming a hydrophobic cavity inside. The cavity of LolA, but
      not that of LolB, is closed and thus inaccessible to the bulk solvent. Previous
      studies suggested that Arg at position 43 of LolA is critical for maintaining
      this closed structure. We show here, through a crystallographic study, that the
      cavity of the LolA(R43L) mutant, in which Leu replaces Arg-43, is indeed open to
      the external milieu. We then found that the binding of a fluorescence probe
      distinguishes the open/close state of the cavity. Furthermore, it was revealed
      that the hydrophobic cavity of LolA opens upon the binding of lipoproteins. Such
      a liganded LolA was found to be inactive in the release of lipoproteins from the
      inner membrane. On the other hand, the liganded LolA became fully functional when
      lipoproteins were removed from LolA by detergent treatment or transferred to
      LolB. Free LolA thus formed was inaccessible to a fluorescence probe. These
      results, taken together, reveal the LolA cycle, in which the hydrophobic cavity
      undergoes opening and closing upon the binding and release of lipoproteins,
      respectively.

PMID- 18617522
TI  - Prions impair bioaminergic functions through serotonin- or catecholamine-derived
      neurotoxins in neuronal cells.
AB  - The conversion of the cellular prion protein, PrP(C), to an abnormal isoform,
      PrP(Sc), is a central event leading to neurodegeneration in prion diseases.
      Deciphering the molecular and cellular changes imparted by PrP(Sc) accumulation
      remains an arduous task due to the small number of cell lines supporting prion
      replication. Here we introduce the 1C11 cell line as a new in vitro model to
      investigate prion pathogenesis. This cell line is a committed neuroectodermal
      progenitor able to differentiate into fully functional serotonergic or
      catecholaminergic neurons. 1C11 cells, which naturally express PrP(C) from the
      undifferentiated state, can be chronically infected with various prion strains.
      Prion infection does not promote any noticeable phenotypic change in the
      progenitor cells nor prevent the onset of the serotonergic and catecholaminergic
      differentiation programs. Pathogenic prions, however, deviate the overall
      neurotransmitter-metabolism in both pathways by decreasing bioamine synthesis,
      storage, and transport, and enhancing catabolism. Noteworthy, oxidized
      derivatives of both serotonin and catecholamines are selectively detected in the
      differentiated progenies of infected cells and contribute to irreversible
      impairment in bioamine synthesis. Finally, the level of PrP(Sc) accumulation,
      that of infectivity, and the extent of all prion-induced changes in infected
      cells appear to be correlated. The report of such specific effects of infection
      on neuronal functions provides a foundation for dissecting the events underlying
      loss of neuronal homeostasis in prion diseases.

PMID- 18617523
TI  - Functional and structural profiling of the human thrombopoietin gene promoter.
AB  - Human thrombopoietin (TPO) is involved in cardiovascular disease as it regulates
      megakaryocyte development and enhances platelet adhesion/aggregation. The THPO
      promoter structure is still controversial. By reverse transcription-PCR, we
      confirm that THPO transcription is cell line-dependently initiated at two
      alternative promoters, which we newly designated P1a and P1. We subsequently
      electrophoretically scanned and resequenced these portions in 95 and 57 patients
      with cardiovascular disease, respectively, and identified seven variants (
      1450/del58bp, C-920T [rs2855306], A-622G, C-413T [rs885838], C+5A, G+115A, and
      C+135T). After subcloning of 1032 bp of THPO P1 in pGL3-basic vector, five
      molecular haplotypes (MolHaps1-5) were observed: [A(-622)-C(-413)-C(+5)-G(+115);
      wild type (wt)], [A(-622)-T(-413)-C(+5)-G(+115)], [G(-622)-T(-413)-C(+5)
      G(+115)], [A(-622)-C(-413)-A(+5)-G(+115)], [A(-622)-C(-413)-C(+5)-A(+115)], and
      analyzed in reporter gene assays in HEK293T and HepG2 cells. MolHaps 2, 4, and 5
      were significantly more active than wt (all p values < or =0.01) in HEK293T
      cells, MolHap3 exerted a substantial loss of promoter activity (p < 0.0001 in
      HEK293T and p < 0.01 in HepG2, compared with wt). Electrophoretic mobility shift
      assays revealed that A-622G and C-413T individually differed from MolHaps in
      their DNA-protein interaction patterns. Supershift and chromatin
      immunoprecipitation assays identified CCAAT/enhancer-binding protein delta as the
      binding protein exclusively for the -622A allelic portion.

PMID- 18617524
TI  - Role of H2-calponin in regulating macrophage motility and phagocytosis.
AB  - The actin cytoskeleton plays a major role in cell motility that is essential for
      the function of phagocytes. Calponin is an actin-associated regulatory protein.
      Here we report the finding of significant levels of the h2 isoform of calponin in
      peripheral blood cells of myeloid lineage. To study the functional significance,
      h2-calponin gene (Cnn2) interrupted mice were constructed. Germ line transmission
      of the Cnn2-flox-neo allele was obtained in chimeras from two independent clones
      of targeted embryonic stem cells. The insertion of the neo(R) cassette into
      intron 2 of the Cnn2 gene resulted in a significant knockdown of h2-calponin
      expression. Removing the frt-flanked neo(R) cassette by FLP1 recombinase rescued
      the knockdown effect. Cre recombinase-induced deletion of the loxP-flanked exon 2
      eliminated the expression of h2-calponin protein. H2-calponin-free mice showed
      reduced numbers of peripheral blood neutrophils and monocytes. H2-calponin-free
      macrophages demonstrated a higher rate of proliferation and faster migration than
      that of h2-calponin-positive cells, consistent with a faster diapedesis of
      peripheral monocytes and neutrophils. H2-calponin-free macrophages showed reduced
      spreading in adhesion culture together with decreased tropomyosin in the actin
      cytoskeleton. The lack of h2-calponin also significantly increased macrophage
      phagocytotic activity, suggesting a novel mechanism to regulate phagocyte
      functions.

PMID- 18617525
TI  - Carbon dioxide transport through membranes.
AB  - Several membrane channels, like aquaporin-1 (AQP1) and the RhAG protein of the
      rhesus complex, were hypothesized to be of physiological relevance for CO(2)
      transport. However, the underlying assumption that the lipid matrix imposes a
      significant barrier to CO(2) diffusion was never confirmed experimentally. Here
      we have monitored transmembrane CO(2) flux (J(CO2)) by imposing a CO(2)
      concentration gradient across planar lipid bilayers and detecting the resulting
      small pH shift in the immediate membrane vicinity. An analytical model, which
      accounts for the presence of both carbonic anhydrase and buffer molecules, was
      fitted to the experimental pH profiles using inverse problems techniques. At pH
      7.4, the model revealed that J(CO2) was entirely rate-limited by near-membrane
      unstirred layers (USL), which act as diffusional barriers in series with the
      membrane. Membrane tightening by sphingomyelin and cholesterol did not alter
      J(CO2) confirming that membrane resistance was comparatively small. In contrast,
      a pH-induced shift of the CO(2) hydration-dehydration equilibrium resulted in a
      relative membrane contribution of about 15% to the total resistance (pH 9.6).
      Under these conditions, a membrane CO(2) permeability (3.2 +/- 1.6 cm/s) was
      estimated. It indicates that cellular CO(2) uptake (pH 7.4) is always USL
      limited, because the USL size always exceeds 1 mum. Consequently, facilitation of
      CO(2) transport by AQP1, RhAG, or any other protein is highly unlikely. The
      conclusion was confirmed by the observation that CO(2) permeability of epithelial
      cell monolayers was always the same whether AQP1 was overexpressed in both the
      apical and basolateral membranes or not.

PMID- 18617526
TI  - Monomeric CFTR in plasma membranes in live cells revealed by single molecule
      fluorescence imaging.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      regulated chloride channel. There is indirect and conflicting evidence about
      whether CFTR exists in cell membranes as monomers, dimers, or higher order
      oligomers. We measured fluorescence intensities and photobleaching dynamics of
      distinct fluorescent spots in cells expressing functional CFTR-green fluorescent
      protein (GFP) chimeras. Intensity analysis of GFP-labeled CFTR in live cells
      showed single-component distributions with mean intensity equal to that of
      purified monomeric GFP, indicating monomeric CFTR in cell membranes. Fluorescent
      spots showed single-step photobleaching, independently verifying that CFTR is
      monomeric. Results did not depend on whether GFP was added to the CFTR N terminus
      or fourth extracellular loop or on whether CFTR chloride conductance was
      stimulated by cAMP agonists. Control measurements with a CFTR chimera containing
      two GFPs showed two-step photobleaching and a single-component intensity
      distribution with mean intensity twice that of monomeric GFP. These results
      provide direct evidence for monomeric CFTR in live cells.

PMID- 18617527
TI  - Activation of Cdk2 stimulates proteasome-dependent truncation of tyrosine
      phosphatase SHP-1 in human proliferating intestinal epithelial cells.
AB  - SHP-1 is expressed in the nuclei of intestinal epithelial cells (IECs). Increased
      SHP-1 expression and phosphatase activity coincide with cell cycle arrest and
      differentiation in these cells. Suspecting the tumor-suppressive properties of
      SHP-1, a yeast two-hybrid screen of an IEC cDNA library was conducted using the
      full-length SHP-1 as bait. Characterization of many positive clones revealed
      sequences identical to a segment of the Cdk2 cDNA sequence. Interaction between
      SHP-1 and Cdk2 was confirmed by co-immunoprecipitations whereby co-precipitated
      Cdk2 phosphorylated SHP-1 protein. Inhibition of Cdk2 (roscovitine) or proteasome
      (MG132) was associated with an enhanced nuclear punctuate distribution of SHP-1.
      Double labeling localization studies with signature proteins of subnuclear
      domains revealed a co-localization between the splicing factor SC35 and SHP-1 in
      bright nucleoplasmic foci. Using Western blot analyses with the anti-SHP-1
      antibody recognizing the C terminus, a lower molecular mass species of 45 kDa was
      observed in addition to the full-length 64-65-kDa SHP-1 protein. Treatment with
      MG132 led to an increase in expression of the full-length SHP-1 protein while
      concomitantly leading to a decrease in the levels of the lower mass 45-kDa
      molecular species. Further Western blots revealed that the 45-kDa protein
      corresponds to the C-terminal portion of SHP-1 generated from proteasome
      activity. Mutational analysis of Tyr(208) and Ser(591) (a Cdk2 phosphorylation
      site) residues on SHP-1 abolished the expression of the amino-truncated 45-kDa
      SHP-1 protein. In conclusion, our results indicate that Cdk2-associated
      complexes, by targeting SHP-1 for proteolysis, counteract the ability of SHP-1 to
      block cell cycle progression of IECs.

PMID- 18617528
TI  - Bidirectional actions of hydrogen peroxide on endothelial nitric-oxide synthase
      phosphorylation and function: co-commitment and interplay of Akt and AMPK.
AB  - Endothelial NO synthase (eNOS) is critically modulated by kinases via the
      phosphorylation of its Ser(1179) (bovine) or Ser(1177) (human) residue. Reactive
      oxygen species such as H(2)O(2) was reported to activate Akt, leading to
      increased eNOS Ser(1179) phosphorylation and activity. But reactive oxygen
      species are also known to attenuate eNOS function in cardiovascular diseases.
      Prior studies showing H(2)O(2)-stimulated eNOS phosphorylation were performed on
      serum-starved cells, and only the short term effect of H(2)O(2) was examined.
      Here we found that the effects of H(2)O(2) on eNOS Ser(1179) phosphorylation and
      function were bidirectional. With endothelial cells cultured with serum, H(2)O(2)
      initially raised eNOS Ser(1179) phosphorylation and activity. However, after the
      peak increase at 30 min, eNOS Ser(1179) phosphorylation dramatically declined.
      Parallel to the alterations of eNOS Ser(1179) phosphorylation, Akt was
      transiently activated by H(2)O(2) and subsequently became dormant. In contrast,
      AMP-activated protein kinase (AMPK) was progressively activated in H(2)O(2)
      treated cells. Blocking Akt activation abolished the initial rise of eNOS
      Ser(1179) phosphorylation after H(2)O(2) treatment. In long term H(2)O(2)-treated
      cells where Akt was deactivated, significant amounts of Ser(1179)-phosphorylated
      eNOS remained. AMPK inhibition eradicated the remaining eNOS Ser(1179)
      phosphorylation. Taken together, these studies revealed that Akt and AMPK
      orchestrated a bidirectional action on eNOS Ser(1179) phosphorylation in H(2)O(2)
      treated cells. Long term H(2)O(2) exposure decreased eNOS Ser(1179)
      phosphorylation, and this might account for the loss of eNOS function in
      cardiovascular diseases where chronic oxidative injury occurs.

PMID- 18617529
TI  - Three-dimensional conformation at the H19/Igf2 locus supports a model of enhancer
      tracking.
AB  - Insight into how the mammalian genome is structured in vivo is key to
      understanding transcriptional regulation. This is especially true in complex
      domains in which genes are coordinately regulated by long-range interactions
      between cis-regulatory elements. The regulation of the H19/Igf2 imprinted region
      depends on the presence of several cis-acting sequences, including a methylation
      sensitive insulator between Igf2 and H19 and shared enhancers downstream of H19.
      Each parental allele has a distinct expression pattern. We used chromosome
      conformation capture to assay the native three-dimensional organization of the
      H19/Igf2 locus on each parental copy. Furthermore, we compared wild-type
      chromosomes to several mutations that affect the insulator. Our results show that
      promoters and enhancers reproducibly co-localize at transcriptionally active
      genes, i.e. the endodermal enhancers contact the maternal H19 and the paternal
      Igf2 genes. The active insulator blocks traffic of the enhancers along the
      chromosome, restricting them to the H19 promoter. Conversely, the methylated
      inactive insulator allows the enhancers to contact the upstream regions,
      including Igf2. Mutations that either remove or inhibit insulator activity allow
      unrestricted access of the enhancers to the whole region. A mutation that allows
      establishment of an enhancer-blocker on the normally inactive paternal copy
      diminishes the contact of the enhancer with the Igf2 gene. Based on our results,
      we propose that physical proximity of cis-acting DNA elements is vital for their
      activity in vivo. We suggest that enhancers track along the chromosome until they
      find a suitable promoter sequence to interact with and that insulator elements
      block further tracking of enhancers.

PMID- 18617530
TI  - Modulation of functional properties of laforin phosphatase by alternative
      splicing reveals a novel mechanism for the EPM2A gene in Lafora progressive
      myoclonus epilepsy.
AB  - The EPM2A gene, encoding the dual-phosphatase laforin, is mutated in a fatal form
      of progressive myoclonus epilepsy known as Lafora disease (LD). The EPM2A gene,
      by differential splicing of its transcripts, is known to encode two laforin
      isoforms having distinct carboxyl termini; a major isoform localized in the
      cytoplasm (laf331), and a minor isoform that is targeted to the nucleus as well
      (laf317). We show here that the two laforin isoforms interact with each other and
      form homo and heterodimers. The homodimer of laf331 display robust phosphatase
      activity, whereas the laf317 homodimer and the laf331-laf317 heterodimer lack
      phosphatase activity. Laf331 binds to glycogen only as a monomeric form. Laf317,
      on the other hand, was unable to bind to glycogen as a homodimer or as a
      heterodimer. Similar to laf331, laf317 interacts with and functions as a
      substrate for the malin ubiquitin ligase--a product of another gene defective in
      LD. Malin, however, shows higher affinity towards laf331 when compared with
      laf317. We have also tested the effect of LD-associated mutations, whose effects
      are restricted to the laf331 isoform, on laf331-laf317 interaction. Two such
      mutations are known and both abolish the interactions between laf317 and laf331
      and their heterodimerization, but not the homodimerization property of laf331.
      Thus, laf317 could function as a dominant-negative regulator of laf331, and
      laf331-specific mutations might affect laf317 functions as well. Thus, our
      findings reveal a novel mechanism for the EPM2A gene function, regulated by
      alternative splicing, in normal as well as disease conditions.

PMID- 18617531
TI  - Zic2-associated holoprosencephaly is caused by a transient defect in the
      organizer region during gastrulation.
AB  - The putative transcription factor ZIC2 is associated with a defect of forebrain
      development, known as Holoprosencephaly (HPE), in humans and mouse, yet the
      mechanism by which aberrant ZIC2 function causes classical HPE is unexplained.
      The zinc finger domain of all mammalian Zic genes is highly homologous with that
      of the Gli genes, which are transcriptional mediators of Shh signalling.
      Mutations in Shh and many other Hh pathway members cause HPE and it has been
      proposed that Zic2 acts within the Shh pathway to cause HPE. We have investigated
      the embryological cause of Zic2-associated HPE and the relationship between Zic2
      and the Shh pathway using mouse genetics. We show that Zic2 does not interact
      with Shh to produce HPE. Moreover, molecular defects that are able to account for
      the HPE phenotype are present in Zic2 mutants before the onset of Shh signalling.
      Mutation of Zic2 causes HPE via a transient defect in the function of the
      organizer region at mid-gastrulation which causes an arrest in the development of
      the prechordal plate (PCP), a structure required for forebrain midline
      morphogenesis. The analysis provides genetic evidence that Zic2 functions during
      organizer formation and that the PCP develops via a multi-step process.

PMID- 18617532
TI  - A systematic RNAi screen reveals involvement of endocytic pathway in neuronal
      dysfunction in alpha-synuclein transgenic C. elegans.
AB  - Mutations or multiplications in alpha-synuclein gene cause familial forms of
      Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild
      type alpha-synuclein as LB occurs as a hallmark lesion of these disorders,
      collectively referred to as synucleinopathies, implicating alpha-synuclein in the
      pathogenesis of synucleinopathy. To identify modifier genes of alpha-synuclein
      induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg
      worms) that overexpress human alpha-synuclein in a pan-neuronal manner. To
      enhance the RNAi effect in neurons, we crossed alpha-synuclein Tg worms with an
      RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to
      nervous system or synaptic functions, and identified 10 genes that, upon
      knockdown, caused severe growth/motor abnormalities selectively in alpha
      synuclein Tg worms. Among these were four genes (i.e. apa-2, aps-2, eps-8 and rab
      7) related to the endocytic pathway, including two subunits of AP-2 complex.
      Consistent with the results by RNAi, crossing alpha-synuclein Tg worms with an
      aps-2 mutant resulted in severe growth arrest and motor dysfunction. alpha
      Synuclein Tg worms displayed a decreased touch sensitivity upon RNAi of genes
      involved in synaptic vesicle endocytosis, and they also showed impaired
      neuromuscular transmission, suggesting that overexpression of alpha-synuclein
      caused a failure in uptake or recycling of synaptic vesicles. Furthermore,
      knockdown of apa-2, an AP-2 subunit, caused an accumulation of phosphorylated
      alpha-synuclein in neuronal cell bodies, mimicking synucleinopathy. Collectively,
      these findings raise a novel pathogenic link between endocytic pathway and alpha
      synuclein-induced neurotoxicity in synucleinopathy.

PMID- 18617534
TI  - ABA inhibits embryo cell expansion and early cell division events during coffee
      (Coffea arabica 'Rubi') seed germination.
AB  - BACKGROUND AND AIMS: Coffee seed germination represents an interplay between the
      embryo and the surrounding endosperm. A sequence of events in both parts of the
      seed determines whether germination will be successful or not. Following previous
      studies, the aim here was to further characterize the morphology of endosperm
      degradation and embryo growth with respect to morphology and cell cycle, and the
      influence of abscisic acid on these processes. METHODS: Growth of cells in a
      fixed region of the axis was quantified from light micrographs. Cell cycle events
      were measured by flow cytometry and by immunocytochemistry, using antibodies
      against beta-tubulin. Aspects of the endosperm were visualized by light and
      scanning electron microscopy. KEY RESULTS: The embryonic axis cells grew
      initially by isodiametric expansion. This event coincided with reorientation and
      increase in abundance of microtubules and with accumulation of beta-tubulin.
      Radicle protrusion was characterized by a shift from isodiametric expansion to
      elongation of radicle cells and further accumulation of beta-tubulin. Early cell
      division events started prior to radicle protrusion. Abscisic acid decreased the
      abundance of microtubules and inhibited the growth of the embryo cells, the
      reorganization of the microtubules, DNA replication in the embryonic axis, the
      formation of a protuberance and the completion of germination. The endosperm cap
      cells had smaller and thinner cell walls than the rest of the endosperm. Cells in
      the endosperm cap displayed compression followed by loss of cell integrity and
      the appearance of a protuberance prior to radicle protrusion. CONCLUSIONS: Coffee
      seed germination is the result of isodiametric growth of the embryo followed by
      elongation, at the expense of integrity of endosperm cap cells. The cell cycle,
      including cell division, is initiated prior to radicle protrusion. ABA inhibits
      expansion of the embryo, and hence subsequent events, including germination.

PMID- 18617533
TI  - Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal.
AB  - During mammalian sex determination, expression of the Y-linked gene Sry shifts
      the bipotential gonad toward a testicular fate by upregulating a feed-forward
      loop between FGF9 and SOX9 to establish SOX9 expression in somatic cells. We
      previously proposed that these signals are mutually antagonistic with
      counteracting signals in XX gonads and that a shift in the balance of these
      factors leads to either male or female development. Evidence in mice and humans
      suggests that the male pathway is opposed by the expression of two signals, WNT4
      and R-SPONDIN-1 (RSPO1), that promote the ovarian fate and block testis
      development. Both of these ligands can activate the canonical Wnt signaling
      pathway. Duplication of the distal portion of chromosome 1p, which includes both
      WNT4 and RSPO1, overrides the male program and causes male-to-female sex reversal
      in XY patients. To determine whether activation of beta-catenin is sufficient to
      block the testis pathway, we have ectopically expressed a stabilized form of beta
      catenin in the somatic cells of XY gonads. Our results show that activation of
      beta-catenin in otherwise normal XY mice effectively disrupts the male program
      and results in male-to-female sex-reversal. The identification of beta-catenin as
      a key pro-ovarian and anti-testis signaling molecule will further our
      understanding of the mechanisms controlling sex determination and the molecular
      mechanisms that lead to sex-reversal.

PMID- 18617535
TI  - Therapy-related acute promyelocytic leukemia caused by hormonal therapy and
      radiation in a patient with recurrent breast cancer.
AB  - We report a patient with therapy-related acute promyelocytic leukemia (APL) that
      may have been caused by regional radiation or hormonal therapy after surgery. A
      36-year-old Japanese woman developed right breast cancer and underwent breast
      conserving surgery and regional radiation to the right breast without adjuvant
      systemic therapy because she wished to preserve her fertility. Two years later,
      she developed multiple bone metastases of breast cancer and received hormonal
      therapy. During the second line hormonal therapy, she developed APL and received
      induction and consolidation chemotherapy with all-trans retinoic acid (ATRA) and
      a combination of anthracycline and cytarabine. After she achieved a complete
      remission (CR) of the APL, her bone metastases of breast cancer progressed. She
      received weekly paclitaxel treatments and her bone marrow function recovered.
      However, 9 months later, her APL relapsed; she achieved a second CR after
      undergoing ATRA therapy again. This patient is thought to be a rare case of
      secondary leukemia, since the leukemia might have been caused by hormonal therapy
      and regional radiation without chemotherapy.

PMID- 18617536
TI  - Randomized controlled trial comparing gastrectomy plus chemotherapy with
      chemotherapy alone in advanced gastric cancer with a single non-curable factor:
      Japan Clinical Oncology Group Study JCOG 0705 and Korea Gastric Cancer
      Association Study KGCA01.
AB  - A randomized controlled trial has started in both Japan and Korea to evaluate the
      role of gastrectomy in the management of incurable advanced gastric cancer (AGC).
      Patients with AGC diagnosed as having a single non-curable factor are randomized
      to gastrectomy plus chemotherapy or chemotherapy alone. Surgeons at 33
      specialized centers in Japan and at 15 high-volume hospitals in Korea will
      recruit 330 patients. Primary end-point is overall survival, and secondary end
      points are progression-free survival and adverse events associated with either
      gastrectomy or chemotherapy.

PMID- 18617537
TI  - Multimarker analysis and imputation of multiple platform pooling-based genome
      wide association studies.
AB  - For many genome-wide association (GWA) studies individually genotyping one
      million or more SNPs provides a marginal increase in coverage at a substantial
      cost. Much of the information gained is redundant due to the correlation
      structure inherent in the human genome. Pooling-based GWA studies could benefit
      significantly by utilizing this redundancy to reduce noise, improve the accuracy
      of the observations and increase genomic coverage. We introduce a measure of
      correlation between individual genotyping and pooling, under the same framework
      that r(2) provides a measure of linkage disequilibrium (LD) between pairs of
      SNPs. We then report a new non-haplotype multimarker multi-loci method that
      leverages the correlation structure between SNPs in the human genome to increase
      the efficacy of pooling-based GWA studies. We first give a theoretical framework
      and derivation of our multimarker method. Next, we evaluate simulations using
      this multimarker approach in comparison to single marker analysis. Finally, we
      experimentally evaluate our method using different pools of HapMap individuals on
      the Illumina 450S Duo, Illumina 550K and Affymetrix 5.0 platforms for a combined
      total of 1 333 631 SNPs. Our results show that use of multimarker analysis
      reduces noise specific to pooling-based studies, allows for efficient integration
      of multiple microarray platforms and provides more accurate measures of
      significance than single marker analysis. Additionally, this approach can be
      extended to allow for imputing the association significance for SNPs not directly
      observed using neighboring SNPs in LD. This multimarker method can now be used to
      cost-effectively complete pooling-based GWA studies with multiple platforms
      across over one million SNPs and to impute neighboring SNPs weighted for the loss
      of information due to pooling.

PMID- 18617538
TI  - Bayesian survival analysis in genetic association studies.
AB  - MOTIVATION: Large-scale genetic association studies are carried out with the hope
      of discovering single nucleotide polymorphisms involved in the etiology of
      complex diseases. There are several existing methods in the literature for
      performing this kind of analysis for case-control studies, but less work has been
      done for prospective cohort studies. We present a Bayesian method for linking
      markers to censored survival outcome by clustering haplotypes using gene trees.
      Coalescent-based approaches are promising for LD mapping, as the coalescent
      offers a good approximation to the evolutionary history of mutations. RESULTS: We
      compare the performance of the proposed method in simulation studies to the
      univariate Cox regression and to dimension reduction methods, and we observe that
      it performs similarly in localizing the causal site, while offering a clear
      advantage in terms of false positive associations. Moreover, it offers
      computational advantages. Applying our method to a real prospective study, we
      observe potential association between candidate ABC transporter genes and
      epilepsy treatment outcomes. AVAILABILITY: R codes are available upon request.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 18617539
TI  - Prevalence of herpes simplex virus type 1 glycoprotein G (gG) and gI genotypes in
      patients with herpetic keratitis.
AB  - AIM: Recent phylogenetic analyses on the herpes simplex virus type 1 (HSV-1)
      genes US4, encoding glycoprotein G (gG) and US7, encoding gI, of clinical HSV-1
      isolates have led to the classification of HSV-1 into three genotypes,
      arbitrarily designated as A, B and C. The prevalence of the HSV-1 gG and gI
      genotypes and their potential disease association was determined in a large
      cohort of patients with herpetic keratitis (HK). METHODS: Primary corneal HSV-1
      isolates of 178 HK patients were genotyped by a PCR-based restriction fragment
      length polymorphism method targeting the viral genes US4 and US7. RESULTS:
      Genotype B was more frequently expressed by the corneal HSV-1 isolates compared
      with genotypes A and C. Fifty-five of 178 corneal isolates (31%) had different
      genotypes in both loci. No clinically relevant associations were observed between
      the HSV-1 genotypes and disease outcome in the HK patients studied. CONCLUSIONS:
      The data presented demonstrate a high frequency of recombinant corneal HSV-1
      isolates and suggest that clinical outcome of HSV-1-induced keratitis is
      independent of a gG or gI genotype.

PMID- 18617540
TI  - Drift of ocular alignment following strabismus surgery. Part 1: using fixed
      scleral sutures.
AB  - AIMS: To evaluate the postoperative alignment drift following traditional
      strabismus surgery utilizing direct attachment of muscle to sclera. METHODS: The
      ocular alignment drift (change from the first postoperative week) of 106 patients
      who underwent scleral fixation strabismus surgery at age 0.5 to 35 years with 5
      years' maximal follow-up was analysed. RESULTS: There was a mean undercorrection
      drift of 4.6 (SD 8.9) prism dioptres (PD) at distance fixation (p = 0.025) and
      3.4 (7.6) PD at near (p = 0.053) for all subjects, and 11.3 (8.6) PD distance (p
      = 0.008) and 10.6 (6.0) PD near (p = 0.016) for exotropic patients. Recession
      surgery produced an undercorrection drift of 5.3 (8.8) PD (p = 0.021) at distance
      fixation. Esotropic patients and those undergoing unilateral recession/resection
      surgery had no significant drift. Patients overcorrected at the 1-week
      postoperative visit later developed an undercorrection drift at distance (10.3
      (7.9) PD, p = 0.002) and near fixation (5.5 (9.2) PD at 36 months, p = 0.041),
      while undercorrected patients showed no significant drift and largely stayed
      undercorrected. CONCLUSION: Fixed scleral-suture strabismus surgery generally
      produces a postoperative undercorrection drift, especially following recession
      surgery, exotropia or overcorrection at the first postoperative week.

PMID- 18617541
TI  - Abnormal fundus autofluorescence patterns in myopic choroidal neovascularisation.
AB  - BACKGROUND/AIMS: To investigate fundus autofluorescence (FAF) findings in eyes
      with myopic choroidal neovascularisation (CNV). METHODS: Observational case
      series. Twenty-seven consecutive eyes with CNV for at least 1 year were included.
      FAF patterns, time after the onset of CNV seen on FAF and FAF changes were
      evaluated. RESULTS: The following patterns were observed: pattern I (n = 2),
      relative hypoautofluorescence around the CNV surrounded by hyperautofluorescence
      a mean of 17 months after CNV onset; pattern II (n = 11), small lobular or
      multilobular well-defined FAF defects within a relatively hypoautofluorescent
      region surrounded by hyperautofluorescence a mean of 35 months after onset;
      pattern III (n = 4), large lobular or multilobular well-defined FAF defects
      surrounded by hyperautofluorescence a mean of 59 months after onset; and pattern
      IV (n = 10), large lobular or crescent-shaped well-defined FAF defects a mean of
      107 months after onset. Well-defined FAF defects corresponded to chorioretinal
      atrophy on colour fundus photographs. During the follow-up period, two eyes with
      pattern I evolved into pattern II. Lobular or multilobular well-defined FAF
      defects enlarged in 11 eyes (pattern II, nine eyes; pattern III, two eyes).
      CONCLUSION: Autofluorescent changes progress over time through pattern grading. A
      pattern classification might be helpful to predict chorioretinal atrophy changes
      around myopic CNV.

PMID- 18617542
TI  - Intracameral bevacizumab effectively reduces aqueous vascular endothelial growth
      factor concentrations in neovascular glaucoma.

PMID- 18617543
TI  - Quantitative analysis of anterior segment optical coherence tomography images:
      the Zhongshan Angle Assessment Program.
AB  - AIM: To describe a new image analysis method and software for anterior chamber
      images obtained by the anterior-segment optical coherence tomography (AS-OCT) and
      to assess its intraobserver and interobserver measurement reproducibility.
      METHODS: Twenty 8-bit greyscale 600x300 AS-OCT images with apparent wide angles
      and 20 images with apparent narrow angles were consecutively selected from a
      database. Two glaucoma fellowship-trained ophthalmologists used proprietary image
      analysis software to analyse the images twice. Algorithms defined the borders and
      curvatures of anterior chamber (AC) structures and measured AC parameters using
      scleral spur location as the only observer input. The intraobserver and
      interobserver reproducibility of scleral spur location and angle parameters was
      calculated in terms of limits of agreement (LOA; mean of differences+/-1.96 SD of
      differences) and coefficient of variation (CV; SD of differences/overall mean).
      RESULTS: The analysis software successfully measured all parameters in all
      images. When the same image was assessed twice by the same grader, the mean
      differences ranged from 0 to 0.010 mm in linear measurements and 0.001 to 0.006
      mm2 in angle area measurements. LOA tended to be greater in the wider angles. The
      upper and lower limit values of LOAs were approximately 1/5 to 1/4 of the overall
      mean. Measurements between two graders had a higher variance. Reproducibility in
      terms of CV was better in wide angles when compared with narrow angles. The
      reproducibility of scleral spur placement between observers was poorer in narrow
      angles (p = 0.001). About 50% of the interobserver variance in angle-area
      measurements was attributable to the variance of scleral spur placement, while
      this proportion was only 10-20% in linear measurements. CONCLUSIONS:
      Determination of angle parameters using semiautomated software leads to
      variability in measurement. Variability increases when more than one observer
      identifies the scleral spur. Variability differs in narrow and open angles, and
      so including both types is essential when evaluating angle-assessment software. A
      fully automated analysis and higher image resolution would likely improve
      quantification of Visante AS-OCT images.

PMID- 18617544
TI  - Medium-term outcomes of safe surgery system trabeculectomies.
AB  - AIM: To assess the safety and success of Safe Surgery System trabeculectomy
      beyond 3 years. METHODS: Consecutive case series of 39 eyes in 32 patients.
      Trabeculectomy was performed using fornix-based conjunctival flap, standard
      trabeculectomy punch, adjustable scleral flap sutures and antimetabolite
      treatment. Primary outcome of surgical failure was defined by two criteria: (A)
      need for further surgery, glaucoma medications or an intraocular pressure (IOP)
      >21 mm Hg during >10% of follow-up; or (B) IOP >15 mm Hg for >10% follow-up. A
      relatively aggressive regime of bleb needling and subconjunctival injections was
      used postoperatively in an attempt to reduce bleb fibrosis and failure. The mean
      follow-up was 42 months (range 25-55). RESULTS: The rate of surgical failure was
      4.4% per eye-year for criterion A, and 8.0% per eye-year for criterion B.
      Complications were few and compared favourably with other published series.
      CONCLUSION: The Safe Surgery System for trabeculectomy provides excellent IOP
      control both during the operation and in the short and medium term
      postoperatively, with few complications or surgical failures.

PMID- 18617545
TI  - Excitation-time-dependent increment in the luminescence of fundus
      autofluorescence.
AB  - AIM: To investigate the excitation-time-dependent increment in luminescence of
      fundus autofluorescence. METHODS: Fundus autofluorescence (FAF) images were
      obtained with a confocal scanning laser ophthalmoscope. Consecutive 60 images of
      each eye were taken at 1 s time intervals immediately after the beginning of
      argon laser excitation. Twenty-one eyes of 21 normal subjects were enrolled in
      the study. To analyse the luminescence of fundus autofluorescence, an 80 x 80
      pixel square selection was placed in a relatively avascular fundus area of each
      consecutive image. Individual grey-scale values of the selected areas were
      recorded, and the time slope was plotted. RESULTS: The time-dependent increment
      of the autofluorescence was observed in all subjects. The average luminosity
      value of subjects at the beginning was calculated as 32.5 mean grey value (MGV),
      and luminosity reached its maximum (45.4 MGV) between 25 and 30 s. CONCLUSION:
      The excitation-time-dependent increment in FAF luminosity should be taken into
      account while acquiring FAF images for quantitative, comparative and longitudinal
      studies.

PMID- 18617546
TI  - A common NYX mutation in Flemish patients with X linked CSNB.
AB  - AIMS: The Schubert-Bornschein type of complete congenital stationary night
      blindness (CSNB) is a genetically heterogeneous retinal disorder. It is
      characterised by a non-progressive disease course, often associated with high
      myopia and nystagmus. So far, mutations in two genes, NYX (nyctalopin) and GRM6
      (metabotropic glutamate receptor 6) have been associated with this form of CSNB.
      The purpose of this study was to identify the genetic defect in affected male
      patients from Flemish families with complete CSNB. METHODS: Probands with CSNB
      from three large Flemish families underwent ophthalmological examination. DNA was
      extracted from peripheral blood, and the coding region of NYX along with parts of
      the 5'UTR and 3'UTR and intronic regions covering the splice sites were PCR
      amplified and sequenced. RESULTS: In the affected individuals of three Flemish
      families with the complete form of CSNB a novel NYX mutation, c.855delG was
      identified. This deletion is predicted to lead to a frameshift mutation,
      p.Asp286ThrfsX62 causing a premature stop codon. CONCLUSION: Previously, both
      single families with different mutations in NYX as well as different families
      with an identical mutation, suggestive of a founder mutation, have been
      described. The c.855delG deletion in NYX seems to be a common mutation associated
      with CSNB in the Flemish population from Belgium. Thus, we suggest performing
      diagnostic testing for CSNB in the Flemish population initially directed towards
      the identification of this mutation. Subsequent screening for other mutations in
      NYX or GRM6 could be performed as a second step.

PMID- 18617547
TI  - Electrophysiological effects of intravitreal Avastin (bevacizumab) in the
      treatment of exudative age-related macular degeneration.
AB  - OBJECTIVE: To examine the sensitivity of the multifocal electroretinogram (mf
      ERG) at measuring changes in retinal electrical activity in response to Avastin
      (bevacizumab) treatment for age-related macular degeneration (ARMD). METHODS:
      Nine subjects with exudative ARMD, not previously treated with bevacizumab in the
      investigated eye, underwent pretreatment testing with mf-ERG and intravenous
      fluorescein angiography (IVFA). A second mf-ERG test was conducted post
      treatment. The P1 response amplitudes were examined for the hexagons
      corresponding to areas of pathology on the IVFA. Intertest variability was
      accounted for by examining areas without pathology. Aggregate responses were also
      generated for central and lesion-associated responses. RESULTS: Changes in P1
      response amplitude correlated with changes in visual acuity (R(2)>0.96). An
      improvement in Snellen visual acuity correlated with a significant improvement in
      P1 response amplitude from lesion associated recordings (p<0.03). Changes in P1
      response amplitudes were not observed when aggregate responses were generated.
      CONCLUSION: This study represents a novel method for assessing an improvement of
      mf-ERG responses. This is the first study to demonstrate a statistically
      significant change in retinal electrical activity postbevacizumab in patients
      with ARMD. This study demonstrates a method for utilising mf-ERG to assess
      changes in retinal electrical activity and to assess the effectiveness of
      treatments such as bevacizumab.

PMID- 18617548
TI  - A role for the aryl hydrocarbon receptor and the dioxin TCDD in rheumatoid
      arthritis.
AB  - OBJECTIVE: Environmental factors are involved in RA pathogenesis and
      epidemiological studies have suggested that smoking is an environmental risk
      factor for RA. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the major
      toxic components in cigarettes. To clarify the biological effects of smoking in
      RA, we investigated the role of TCDD in RA pathogenesis. METHODS: Human synovial
      tissue was obtained from RA and OA patients and aryl hydrocarbon receptor (AhR)
      expression in these tissues was evaluated using immunohistochemistry and real
      time PCR. Expression of various cytokines was measured by real-time PCR following
      stimulation of RA synoviocytes with different concentrations of TCDD. To study
      the role of AhR, we treated RA synoviocytes with alpha-naphthoflavone, a known
      AhR antagonist. To evaluate which signal transduction pathways were stimulated by
      the TCDD-AhR interaction, we used inhibitors of nuclear factor-kappaB (NF-kappaB)
      and extra-cellular stimulus-activated kinase (ERK). RESULTS: Higher AhR mRNA and
      protein levels were observed in RA synovial tissue than in OA tissue. TCDD up
      regulated the expression of IL-1beta, IL-6 and IL-8 through binding to AhR, and
      this effect was transmitted via the NF-kappaB and ERK signalling cascades. AhR
      expression in synovial cells was up-regulated by TNF-alpha. CONCLUSION: TNF-alpha
      activates AhR expression in RA synovial tissue, and that cigarette smoking and
      exposure to TCDD enhances RA inflammatory processes. TCDD induces inflammatory
      cytokines via its association with AhR, resulting in stimulation of the NF-kappaB
      and ERK signalling cascades. Thus TCDD exposure, such as smoking exacerbates RA
      pathophysiology.

PMID- 18617550
TI  - Comment on: Use of parenteral methotrexate significantly reduces the need for
      biological therapy.

PMID- 18617551
TI  - Polymorphism in the 5' regulatory region of the B-lymphocyte activating factor
      gene is associated with the Ro/La autoantibody response and serum BAFF levels in
      primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the association between haplotypes in the 5' regulatory
      region of the B-lymphocyte activating factor (BAFF) gene, disease susceptibility
      and serum BAFF (s-BAFF) levels in Caucasian primary SS (pSS) patients. METHODS:
      Case-control study in an established pSS cohort with PCR-RFLP genotyping for four
      SNPs (-2841 T-->C, -2704 T-->C, -2701 T-->A, -871 C-->T), which tag a haplotype
      block in the 5' regulatory region of the BAFF gene and s-BAFF determination by
      ELISA. RESULTS: s-BAFF levels were elevated in Ro/La-positive pSS patients (n =
      85, 1770 pg/ml) compared with both Ro/La-negative pSS patients (n = 27, 1193
      pg/ml) and controls (n = 59, 1171 pg/ml), P < 0.001. s-BAFF increased with
      diversification of the anti-Ro/La antibody response, but was not correlated with
      age, RF or immunoglobulin G levels. There were four common BAFF haplotypes. While
      the CTAT haplotype was associated with Ro/La-positive pSS [odds ratio (OR) 2.6;
      95% CI 1.7, 4.1; P = 0.00004], the TTTT haplotype was associated with elevated s
      BAFF in autoantibody-positive pSS (n = 85; 88% females; P = 0.008). The shared 
      871 T allele had no independent contribution to disease susceptibility or s-BAFF.
      CONCLUSIONS: Disease susceptibility for Ro/La-positive pSS is increased with the
      CTAT haplotype, but not associated with high s-BAFF levels. Elevated s-BAFF
      levels in pSS are associated with the TTTT haplotype and may be a secondary
      phenomenon in Ro/La-positive pSS. While both haplotypes carry the -871 T allele,
      this allele is not independently associated with disease susceptibility.

PMID- 18617552
TI  - Effect of systemically administered low potassium dextran solution on oxidative
      stress in a rat model of lung ischemia.
AB  - Systemic administration of the low-potassium dextran solution on the peripheral
      oxidative stress was evaluated in an animal model of lung ischemia-reperfusion in
      rats. In one experiment, male Wistar rats were divided into two groups (n=5): one
      received intravenous saline, whereas in the other the animals were given
      intravenous low potassium dextran solution. In another experiment, male Wistar
      rats were divided into four groups (n=5): control, ischemia, saline and low
      potassium dextran. Except for the control animals, all groups were submitted to
      left hilar clamping for 30 min, followed by reperfusion for 30 min. Saline or low
      potassium dextran was administered intravenously immediately before clamp
      removal. In the first experiment there were no significant differences in lipid
      peroxidation. Total radical trapping potential measurements showed a significant
      increase in animals receiving low potassium dextran; in the second experiment,
      there was an increase in lipid peroxidation in both saline and ischemia groups
      compared to controls, and low potassium dextran. Low potassium dextran group
      showed an increase in total radical trapping potential measurements compared to
      all other groups. Ischemia-reperfusion injury mediated by reactive oxygen species
      was attenuated by the systemic use of low potassium dextran in this animal model
      of ischemia-reperfusion of the lung.

PMID- 18617553
TI  - Donor cryopreserved rib allografts for chest wall reconstruction.
AB  - Reconstruction after large chest wall resections must ensure not only anatomical
      coverage but a normal respiratory function, specially in the case of associated
      ventilatory disturbance. Since prosthetic reconstruction can present some
      problems such as rejection, excessive rigidity or infection, bone grafts have
      been proposed as an alternative to synthetic materials, due to their
      effectiveness and capability of integration with host tissues. Although iliac
      bone allograft or autologous ribs harvested from the opposite operative side are
      described for reconstruction, we present here the first reported clinical case of
      donor cryopreserved rib allografts use after extensive chest wall resection in a
      patient with severe COPD, showing excellent short-term results in the absence of
      pulmonary function impairment.

PMID- 18617554
TI  - Impact of pre-existing conditions, age and the length of cardiopulmonary bypass
      on postoperative outcome after repair of the ascending aorta and aortic arch for
      aortic aneurysms and dissections.
AB  - BACKGROUND: Repair of the ascending aorta and aortic arch carries a high
      morbidity and mortality, which can be complicated by the often emergent nature of
      the intervention. METHODS: We retrospectively evaluated the morbidity, mortality,
      and long-term survival in 101 patients who underwent repair of ascending aorta
      and aortic arch. Depending on the urgency of the operation, the patients were
      categorized as elective (EL, n=82) or emergent (EM, n=19). Log-rank-list and SPS
      were used to evaluate the data. RESULTS: The average age was 58+/-16 years. The
      aortic diameter was 5.5+/-1 cm in the EL group and 6.1+/-1.4 cm for EM group. The
      aortic dissection in EL and EM groups was 15% and 79%, respectively. The mean
      circulatory arrest time (n=32 patients) was 38+/-18.5 min. The overall 30-day
      mortality was 4%: 0% for the EL group and 26% for the EM group. The overall 6
      month mortality was 8%: 3.7% and 26% in EL and EM groups, respectively. Overall
      CVA was 3%: 0% in the EL group and 15.7% in the EM group. The mean CPB time was
      176+/-81 min. The prolonged CPB time correlated with increased need for blood
      transfusion. The LOS was 12+/-8 days and correlated with increasing age (95% CI
      0.06860-0.2307, P=0.0004), with NYHA stage of patients at the time of surgery
      (95% confidence intervals, 1.328-4.202, P=0.0003), with left ventricular ejection
      fraction (95% CI 0.2357 to -0.003029, P=0.0442) and with postoperative atrial
      fibrillation (95% CI 0.1192-0.4745, P=0.0018). The average ICU stay was 123+/-145
      h. A prolonged CPB time resulted in extended ICU stay (95% CI 0.3655-1.486,
      P=0.0014). Further, the length of ICU stay correlated with NYHA status (95% CI
      19.98-73.42, P=0.0008), age (95% confidence intervals 0.01668-3.761, P=0.0477),
      urgency of surgery (95% CI 65.00-124.0, P<0.0001), and length of CPB time (95% CI
      0.3655-1.486, P=0.0014). CONCLUSION: Emergent operations are associated with high
      morbidity and mortality. Pre-existing heart failure, advanced age, and prolonged
      cardiopulmonary bypass are associated with prolonged monitoring in the ICU.

PMID- 18617555
TI  - High body mass alters colonic sensory-motor function and transit in humans.
AB  - There is increased prevalence of abdominal pain and diarrhea and decreased
      gastric sensation with increased body mass index (BMI). Our hypothesis is that
      increased BMI is associated with increased colonic motility and sensation. The
      study aim was to assess effect of BMI on colonic sensory and motor functions and
      transit. We used a database of colonic tone, compliance, and perception of
      distensions measured by intracolonic, barostat-controlled balloon, and
      gastrointestinal transit was measured by validated scintigraphy in healthy obese
      and nonobese subjects. Regression analysis was applied to assess the association
      of BMI with colonic sensory and motor functions. We included adjustments for sex
      differences, age, height, balloon volumes during distension, and psychological
      stress. Among 165 participants (87 women, 78 men), increased BMI was associated
      with decreased colonic compliance (P < 0.006, adjusted), decreased pain rating
      during distensions (P = 0.02, adjusted), and a higher threshold for pain (P =
      0.042, adjusted). Sensation for gas, colonic tone, and contraction after meal
      ingestion were not significantly associated with BMI. Transit was assessed in 72
      participants (41 women, 31 men); colonic transit was faster with BMI >30 kg/m(2)
      (P = 0.003 unadjusted, P = 0.08 adjusted for gender). In conclusion, BMI >25
      kg/m(2) is associated with decreased colonic compliance and pain sensation;
      colonic transit is accelerated particularly with BMI >30 kg/m(2) in women. These
      data suggest that colonic dysfunction may contribute to diarrhea, but the cause
      of increased abdominal pain in obesity is not explained by the studies of colonic
      sensation and requires further study of afferent, spinal, and central mechanisms.

PMID- 18617556
TI  - Differences in activity and phosphorylation of MAPK enzymes in esophageal
      squamous cells of GERD patients with and without Barrett's esophagus.
AB  - We hypothesized that, in esophageal squamous epithelial cells, there are
      differences among individuals in the signal transduction pathways activated by
      acid reflux that might underlie the development of Barrett's esophagus. To
      explore that hypothesis, we immortalized nonneoplastic, esophageal squamous cells
      from patients with gastroesophageal reflux disease (GERD) with (NES-B3T) and
      without (NES-G2T) Barrett's esophagus and used those cells to study acid effects
      on MAPK proteins. During endoscopy in patients with GERD with and without
      Barrett's esophagus, we took biopsy specimens from the distal squamous esophagus
      to study MAPK proteins before and after esophageal perfusion with 0.1 N HCl. We
      used immunoblotting and Western blotting to study MEK1/2 phosphorylation at two
      activating sites (serines 217/221), MEK1 phosphorylation at an inhibitory site
      (threonine 286), and MEK1/2 activity. After acid exposure, both cell lines
      exhibited increased MEK1/2 phosphorylation at the activating sites; the NES-B3T
      cells had higher levels of MEK1 phosphorylation at the inhibitory site, however,
      and only the NES-G2T cells showed an acid-induced increase in MEK1/2 activity.
      Similarly, in the squamous epithelium of patients with GERD with and without
      Barrett's esophagus, acid perfusion increased MEK1/2 phosphorylation at the
      activating sites in both patient groups; the Barrett's patients had higher levels
      of MEK1 phosphorylation at the inhibitory site, however, and only the patients
      without Barrett's demonstrated an acid-induced increase in ERK1/2
      phosphorylation. In esophageal squamous cell lines and biopsies from patients
      with GERD with and without Barrett's esophagus, we have found differences in MAPK
      pathways activated by acid exposure. We speculate that these differences might
      underlie the development of Barrett's metaplasia.

PMID- 18617558
TI  - Sodium tungstate decreases sucrase and Na+/D-glucose cotransporter in the jejunum
      of diabetic rats.
AB  - Sodium tungstate reduces glycemia and reverts the diabetic phenotype in several
      induced and genetic animal models of diabetes. Oral administration of this
      compound has recently emerged as an effective treatment for diabetes. Here we
      examined the effects of 30 days of oral administration of tungstate on
      disaccharidase and Na+/D-glucose cotransporter (SGLT1) activity in the jejunum of
      control and streptozotocin-induced diabetic rats. Diabetes increased sucrase
      specific activity in the jejunal mucosa but did not affect the activity of
      lactase, maltase, or trehalase. The abundance and the maximal rate of transport
      of SGLT1 in isolated brush-border membrane vesicles also increased. Tungstate
      decreased sucrase activity and normalized SGLT1 expression and activity in the
      jejunum of diabetic rats. Furthermore, tungstate did not change the affinity of
      SGLT1 for d-glucose and had no effect on the diffusional component. In control
      animals, tungstate had no effect on disaccharidases or SGLT1 expression. Northern
      blot analysis showed that the amount of specific SGLT1 mRNA was the same in the
      jejunum from all experimental groups, thereby indicating that changes in SGLT1
      abundance are due to posttranscriptional mechanisms. We conclude that the
      antidiabetic effect of tungstate is partly due to normalization of the activity
      of sucrase and SGLT1 in the brush-border membrane of enterocytes.

PMID- 18617557
TI  - Colitis immunoregulation by CD8+ T cell requires T cell cytotoxicity and B cell
      peptide antigen presentation.
AB  - Deficient immunoregulation by CD4+ T cells is an important susceptibility trait
      for inflammatory bowel disease, but the role of other regulatory cell types is
      less understood. This study addresses the role and mechanistic interaction of B
      cells and CD8+ T cells in controlling immune-mediated colitis. The genetic
      requirements for B cells and CD8+ T cells to confer protective immunoregulation
      were assessed by cotransfer with colitogenic Galphai2-/- T cells into immune
      deficient mice. Disease activity in Galphai2-/- T cell recipients was evaluated
      by CD4+ T intestinal lymphocyte abundance, cytokine production levels, and large
      intestine histology. B cells deficient in B7.1/B7.2, CD40, major
      histocompatibility complex (MHC) II (Abb), or native B cell antigen receptor
      (MD4) were competent for colitis protection. However, transporter-1-deficient B
      cells failed to protect, indicating a requirement for peptide MHC I presentation
      to CD8+ T cells. CD8+ T cells deficient in native T cell receptor repertoire (OT
      1) or cytolysis (perforin-/-) also were nonprotective. These finding reveal an
      integrated role for antigen-specific perforin-dependent CD8+ T cell cytotoxicity
      in colitis immunoregulatory and its efficient induction by a subset of mesenteric
      B lymphocytes.

PMID- 18617559
TI  - Adaptive HNE-Nrf2-HO-1 pathway against oxidative stress is associated with acute
      gastric mucosal lesions.
AB  - Disturbance of the microcirculation and generation of reactive oxygen species are
      crucial in producing acute gastric mucosal lesions (AGML). To understand the
      protective mechanism against mucosal injury and oxidative stress in the stomach,
      we investigated sequential expression and localization of a product of lipid
      peroxidation and a chemical mediator of the oxidative response array, 4
      hydroxynonenal (HNE), transcriptional factor, NF-E2-related factor (Nrf2), and
      the inducible heme oxygenase (HO-1) in the injured stomach. AGML was produced by
      intragastric administration of 0.6 N HCl in male rats. Expression and
      localization of HNE, Nrf2, and HO-1 were investigated by Western blotting,
      immunohistochemistry, real-time RT-PCR, and in situ hybridization histochemistry.
      Mucosal lesions and expression of HNE and HO-1 were assessed by prior treatment
      with the PGI2 analog beraprast or after sensory denervation by pretreatment with
      capsaicin. Mucosal lesions were assessed by prior treatment with a HO-1
      inhibitor, zinc protoporphyrin (ZnPP). After AGML, increased generation of HNE
      was observed in the injured mucosa and the surrounding submucosa, followed by
      nuclear translocation of Nrf2 and upregulation of HO-1 in the macrophages located
      in the margin of the injured mucosa and in the submucosa. Pretreatment with
      beraprost attenuated AGML and downregulated the expression of HNE and HO-1, while
      sensory denervation aggravated AGML and upregulated the expression of HNE and HO
      1. Pretreatment with ZnPP also aggravated AGML. The sequential HNE-Nrf2-HO-1
      pathway in the gastric mucosal cells and the macrophages is involved in an
      adaptive mechanism against oxidative stress after AGML.

PMID- 18617560
TI  - Cessation of daily exercise dramatically alters precursors of hepatic steatosis
      in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
AB  - The purpose of this study was to delineate potential mechanisms initiating the
      onset of hepatic steatosis following the cessation of daily physical activity.
      Four-week-old, hyperphagic/obese Otsuka Long-Evans Tokushima Fatty rats were
      given access to voluntary running wheels for 16 weeks to prevent the development
      of hepatic steatosis. The animals were then suddenly transitioned to a sedentary
      condition as wheels were locked (wheel lock; WL) for 5 h (WL5), 53 h (WL53) or
      173 h (WL173). Importantly after the cessation of daily exercise (5-173 h), no
      changes occurred in body weight, fat pad mass (omental and retroperitoneal), food
      intake, serum insulin, hepatic triglycerides or in the exercise-suppressed
      hepatic stearoyl-CoA desaturase-1 and peroxisome proliferator-activated receptor
      gamma protein content. However, complete hepatic fatty acid oxidation and
      mitochondrial enzyme activities were highest at WL5 and WL53 and dropped
      significantly to SED levels by WL173. In addition, cessation of daily exercise
      quickly increased the hepatic protein contents of fatty acid synthase and acetyl
      coenzyme A carboxylase (ACC), reduced ACC phosphorylation status, and
      dramatically increased hepatic malonyl-CoA concentration. This study is the first
      to show that the sudden cessation of daily exercise in a hyperphagic/obese model
      activates a subgroup of precursors and processes known to initiate hepatic
      steatosis, including decreased hepatic mitochondrial oxidative capacity,
      increased hepatic expression of de novo lipogenesis proteins, and increased
      hepatic malonyl CoA levels; each probably increasing the susceptibility to non
      alcoholic fatty liver disease.

PMID- 18617561
TI  - Synaptic physiology of direction selectivity in the retina.
AB  - Detection of the direction of image movement is accomplished first in the retina
      by an elegant neuronal circuit, which integrates multiple levels of spatially
      asymmetric synaptic interactions among subsets of bipolar, amacrine and ganglion
      cells. Central to these interactions is the asymmetric GABAergic inhibition
      exerted by the starburst amacrine cell (SAC), a cholinergic and GABAergic
      interneuron with a radially symmetric dendritic tree. SACs make reciprocal
      GABAergic synapses on each other to create a direct inhibitory receptive field
      surround, which suppresses the response of each SAC to centripetal image
      movement. Each radially projecting branch of a SAC responds to image movement
      with a centrifugal bias and, through directionally asymmetric synaptic
      connections with the dendrites of direction-selective ganglion cells (DSGCs),
      exerts a spatially offset inhibition that vetoes the response of DSGCs to image
      movement in a specific (null) direction. Recent physiological studies have
      greatly advanced our understanding of the mechanism of direction selectivity and
      also revealed a new level of complexity that remains to be understood.

PMID- 18617562
TI  - Mechanisms of response homeostasis during retinocollicular map formation.
AB  - The mechanisms of Hebbian synaptic plasticity have been widely hypothesized to
      play a role in the activity-dependent development of neural circuits. However,
      these mechanisms are inherently unstable and would lead to the runaway excitation
      or depression of circuits if left unchecked. In the last decade, a number of
      elegant studies have demonstrated that homeostatic plasticity mechanisms exist to
      stabilize neural networks and maintain the constancy of neuronal output in
      response to changes in activity levels. These include synaptic scaling, sliding
      threshold models of synaptic plasticity, dynamic regulation of the number and
      strength of synapses, and bidirectional control of intrinsic excitability.
      Recently, we showed that the total synaptic input onto individual neurons of the
      mouse superior colliculus is preserved regardless of the size of their visual
      receptive fields, a phenomenon we term 'response homeostasis'. Here, we argue
      that regulating the capacity for synaptic plasticity and controlling the number
      and strength of retinocollicular inputs can preserve collicular neuron output,
      and we present evidence that changes in intrinsic excitability are not associated
      with response homeostasis. We also review findings from a number of different
      mutant mice and discuss whether and how different cellular mechanisms may
      underlie response homeostasis. Combined with other studies, our work reveals an
      important role for homeostatic mechanisms in regulating functional connectivity
      during the construction of receptive fields and the refinement of topographic
      maps.

PMID- 18617563
TI  - Aldosterone increases KCa1.1 (BK) channel-mediated colonic K+ secretion.
AB  - Mammalian K(+) homeostasis results from highly regulated renal and intestinal
      absorption and secretion, which balances the unregulated K(+) intake. Aldosterone
      is known to enhance both renal and colonic K(+) secretion. In mouse distal colon
      K(+) secretion occurs exclusively via luminal K(Ca)1.1 (BK) channels. Here we
      investigate if aldosterone stimulates colonic K(+) secretion via BK channels.
      Luminal Ba(2+) and iberiotoxin (IBTX)-sensitive electrogenic K(+) secretion was
      measured in Ussing chambers. In vivo aldosterone was augmented via a high K(+)
      diet. High K(+) diet led to a 2-fold increase of luminal Ba(2+) and IBTX
      sensitive short-circuit current in distal mouse colonic mucosa. This effect was
      absent in BK alpha-subunit-deficient (BK(-/-)) mice. The resting and diet-induced
      K(+) secretion was stimulated by luminal ionomycin. In BK(-/-) mice luminal
      ionomycin did not stimulate K(+) secretion. In vitro addition of aldosterone
      likewise triggered a 2-fold increase in K(+) secretion, which was inhibited by
      the mineralocorticoid receptor antagonist spironolactone and the BK channel
      blocker IBTX. Semi-quantification of mRNA from colonic crypts showed up
      regulation of BK alpha- and beta(2)-subunits in high K(+) diet mice. The BK
      channel could be detected luminally in colonic crypt cells by
      immunohistochemistry. The expression level of the channel in the luminal membrane
      was strongly up-regulated in K(+)-loaded animals. Taken together, these data
      strongly suggest that aldosterone-induced K(+) secretion occurs via increased
      expression of luminal BK channels.

PMID- 18617564
TI  - Functional circuitry of visual adaptation in the retina.
AB  - The visual system continually adjusts its sensitivity, or 'adapts', to the
      conditions of the immediate environment. Adaptation increases responses when
      input signals are weak, to improve the signal-to-noise ratio, and decreases
      responses when input signals are strong, to prevent response saturation. Retinal
      ganglion cells adapt primarily to two properties of light input: the mean
      intensity and the variance of intensity over time (contrast). This review focuses
      on cellular mechanisms for contrast adaptation in mammalian retina. High contrast
      over the ganglion cell's receptive field centre reduces the gain of spiking
      responses. The mechanism for gain control arises partly in presynaptic bipolar
      cell inputs and partly in the process of spike generation. Following strong
      contrast stimulation, ganglion cells exhibit a prolonged after-hyperpolarization,
      driven primarily by suppression of glutamate release from presynaptic bipolar
      cells. Ganglion cells also adapt to high contrast over their peripheral receptive
      field. Long-range adaptive signals are carried by amacrine cells that inhibit the
      ganglion cell directly, causing hyperpolarization, and inhibit presynaptic
      bipolar terminals, reducing gain of their synaptic output. Thus, contrast
      adaptation in ganglion cells involves multiple synaptic and intrinsic mechanisms
      for gain control and hyperpolarization. Several forms of adaptation in ganglion
      cells originate in presynaptic bipolar cells.

PMID- 18617565
TI  - Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular
      transient receptor potential channel TRPC6.
AB  - We investigated the inhibitory role of the nitric oxide (NO)-cGMP-protein kinase
      G (PKG) pathway on receptor-activated TRPC6 channels in both a heterologous
      expression system (HEK293 cells) and A7r5 vascular myocytes. Cationic currents
      due to TRPC6 expression were strongly suppressed (by approximately 70%) by a NO
      donor SNAP (100 microm) whether it was applied prior to muscarinic receptor
      stimulation with carbachol (CCh; 100 microm) or after G-protein activation with
      intracellular perfusion of GTPgammaS (100 microm). A similar extent of
      suppression was also observed with a membrane-permeable analogue of cGMP, 8Br
      cGMP (100 microm). The inhibitory effects of SNAP and 8Br-cGMP on TRPC6 channel
      currents were strongly attenuated by the presence of inhibitors for guanylyl
      cyclase and PKG such as ODQ, KT5823 and DT3. Alanine substitution for the PKG
      phosphorylation candidate site at T69 but not at other sites (T14A, S28A, T193A,
      S321A) of TRPC6 similarly attenuated the inhibitory effects of SNAP and 8Br-cGMP.
      SNAP also significantly reduced single TRPC6 channel activity recorded in the
      inside-out configuration in a PKG-dependent manner. SNAP-induced PKG activation
      stimulated the incorporation of (32)P into wild-type and S321A-mutant TRPC6
      proteins immunoprecipitated by TRPC6-specific antibody, but this was greatly
      attenuated in the T69A mutant. SNAP or 8Br-cGMP strongly suppressed TRPC6-like
      cation currents and membrane depolarization evoked by Arg(8)-vasopressin in A7r5
      myocytes. These results strongly suggest that TRPC6 channels can be negatively
      regulated by the NO-cGMP-PKG pathway, probably via T69 phosphorylation of the N
      terminal. This mechanism may be physiologically important in vascular tissues
      where NO is constantly released from vascular endothelial cells or nitrergic
      nerves.

PMID- 18617566
TI  - Phosphate metabolite concentrations and ATP hydrolysis potential in normal and
      ischaemic hearts.
AB  - To understand how cardiac ATP and CrP remain stable with changes in work rate - a
      phenomenon that has eluded mechanistic explanation for decades - data from
      (31)phosphate-magnetic resonance spectroscopy ((31)P-MRS) are analysed to
      estimate cytoplasmic and mitochondrial phosphate metabolite concentrations in the
      normal state, during high cardiac workstates, during acute ischaemia and reactive
      hyperaemic recovery. Analysis is based on simulating distributed heterogeneous
      oxygen transport in the myocardium integrated with a detailed model of cardiac
      energy metabolism. The model predicts that baseline myocardial free inorganic
      phosphate (P(i)) concentration in the canine myocyte cytoplasm - a variable not
      accessible to direct non-invasive measurement - is approximately 0.29 mm and
      increases to 2.3 mm near maximal cardiac oxygen consumption. During acute
      ischaemia (from ligation of the left anterior descending artery) P(i) increases
      to approximately 3.1 mm and ATP consumption in the ischaemic tissue is reduced
      quickly to less than half its baseline value before the creatine phosphate (CrP)
      pool is 18% depleted. It is determined from these experiments that the maximal
      rate of oxygen consumption of the heart is an emergent property and is limited
      not simply by the maximal rate of ATP synthesis, but by the maximal rate at which
      ATP can be synthesized at a potential at which it can be utilized. The critical
      free energy of ATP hydrolysis for cardiac contraction that is consistent with
      these findings is approximately -63.5 kJ mol(-1). Based on theoretical findings,
      we hypothesize that inorganic phosphate is both the primary feedback signal for
      stimulating oxidative phosphorylation in vivo and also the most significant
      product of ATP hydrolysis in limiting the capacity of the heart to hydrolyse ATP
      in vivo. Due to the lack of precise quantification of P(i) in vivo, these
      hypotheses and associated model predictions remain to be carefully tested
      experimentally.

PMID- 18617567
TI  - Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary
      stretch receptor (Breuer-Hering) reflex pathway.
AB  - The Breuer-Hering inflation reflex is initiated by activation of the slowly
      adapting pulmonary stretch receptor afferents (SARs), which monosynaptically
      activate second-order relay neurones in the dorsal medullary nucleus of the
      solitary tract (NTS). Here we demonstrate that during lung inflation SARs release
      both ATP and glutamate from their central terminals to activate these NTS
      neurones. In anaesthetized and artificially ventilated rats, ATP- and glutamate
      selective microelectrode biosensors placed in the NTS detected rhythmic release
      of both transmitters phase-locked to lung inflation. This release of ATP and
      glutamate was independent of the centrally generated respiratory rhythm and could
      be reversibly abolished during the blockade of the afferent transmission in the
      vagus nerve by topical application of local anaesthetic. Microionophoretic
      application of ATP increased the activity of all tested NTS second-order relay
      neurones which receive monosynaptic inputs from the SARs. Unilateral
      microinjection of ATP into the NTS site where pulmonary stretch receptor
      afferents terminate produced central apnoea, mimicking the effect of lung
      inflation. Application of P2 and glutamate receptor antagonists (pyridoxal-5'
      phosphate-6-azophenyl-2',4'-disulphonic acid, suramin and kynurenic acid)
      significantly decreased baseline lung inflation-induced firing of the second
      order relay neurones. These data demonstrate that ATP and glutamate are released
      in the NTS from the central terminals of the lung stretch receptor afferents,
      activate the second-order relay neurones and hence mediate the key respiratory
      reflex - the Breuer-Hering inflation reflex.

PMID- 18617568
TI  - Graded sympatholytic effect of exogenous ATP on postjunctional alpha-adrenergic
      vasoconstriction in the human forearm: implications for vascular control in
      contracting muscle.
AB  - Recent evidence suggests that adenosine triphosphate (ATP) can inhibit
      vasoconstrictor responses to endogenous noradrenaline release via tyramine in the
      skeletal muscle circulation, similar to what is observed in contracting muscle.
      Whether this involves direct modulation of postjunctional alpha-adrenoceptor
      responsiveness, or is selective for alpha(1)- or alpha(2)-receptors remains
      unclear. Therefore, in Protocol 1, we tested the hypothesis that exogenous ATP
      can blunt direct postjunctional alpha-adrenergic vasoconstriction in humans. We
      measured forearm blood flow (FBF; Doppler ultrasound) and calculated the vascular
      conductance (FVC) responses to local intra-arterial infusions of phenylephrine
      (alpha(1)-agonist) and dexmedetomidine (alpha(2)-agonist) during moderate
      rhythmic handgrip exercise (15% maximum voluntary contraction), during a control
      non-exercise vasodilator condition (adenosine), and during ATP infusion in eight
      young adults. Forearm hyperaemia was matched across all conditions. Forearm
      vasoconstrictor responses to direct alpha(1)-receptor stimulation were blunted
      during exercise versus adenosine (DeltaFVC = -11 +/- 3% versus -39 +/- 5%; P<
      0.05), and were abolished during ATP infusion (-3 +/- 2%). Similarly,
      vasoconstrictor responses to alpha(2)-receptor stimulation were blunted during
      exercise versus adenosine (-13 +/- 4% versus -40 +/- 8%; P< 0.05), and were
      abolished during ATP infusion (-4 +/- 4%). In Prototol 2 (n = 10), we tested the
      hypothesis that graded increases in ATP would reduce alpha(1)-mediated
      vasoconstriction in a dose-dependent manner compared with vasodilatation evoked
      via adenosine. Forearm vasoconstrictor responses during low dose adenosine (-38
      +/- 3%) and ATP (-33 +/- 2%) were not significantly different from rest (-40 +/-
      3%; P> 0.05). In contrast, vasoconstrictor responses during moderate (-22 +/- 6%)
      and high dose ATP (-8 +/- 5%) were significantly blunted compared with rest,
      whereas the responses during adenosine became progressively greater (moderate = 
      48 +/- 4%, P = 0.10; high = -53 +/- 6%, P< 0.05). We conclude that exogenous ATP
      is capable of blunting direct postjunctional alpha-adrenergic vasoconstriction,
      that this involves both alpha(1)- and alpha(2)-receptor subtypes, and that this
      is graded with ATP concentrations. Collectively, these data are consistent with
      the conceptual framework regarding how muscle blood flow and vascular tone are
      regulated in contracting muscles of humans.

PMID- 18617569
TI  - Modifications of the interactions in the motor networks when a movement becomes
      automatic.
AB  - A crucial feature of the motor system is the ability to control some movements
      automatically. We have previously shown that all parts of the motor networks
      reduce their activity with automaticity, and, while this change may indicate
      increased efficiency in terms of neural processing, it is not clear how motor
      skill can be maintained after a reduction of neural activity. In the current
      study, we used functional MRI (fMRI) to investigate influences on the effective
      connectivity of the brain motor networks when movements become automatic.
      Subjects practiced a sequential movement until they could execute it
      automatically, and task-related brain fMRI activation was measured before and
      after they achieved automaticity. Using the psychophysiological interaction (PPI)
      method, we found that the cerebellum, cingulate motor area, supplementary motor
      area, and putamen had significantly greater connectivity, whereas the precuneus
      had less connectivity in the motor networks at the automatic stage. Our findings
      demonstrate that the importance of the attention networks decrease when movements
      become automatic. Moreover, the process of automaticity is accompanied by a
      strengthened interaction of central motor networks even though the magnitude of
      the activation is decreased. We speculate that this increase in connectivity
      reflects more efficient neural coding of movement at the automatic stage.

PMID- 18617571
TI  - Commentary: multiple risk models in pediatric research--considering the context
      that shapes children's health.

PMID- 18617570
TI  - AKAP150-anchored PKA activity is important for LTD during its induction phase.
AB  - Protein kinase A (PKA) is thought to tonically maintain an enhanced level of
      postsynaptic AMPA receptor responses. Injection of PKA inhibitory peptides leads
      to a run-down of AMPA receptor responses and prevents long-term depression (LTD).
      This run-down of AMPA receptor activity was proposed to occlude a further
      reduction that would otherwise constitute LTD. PKA is recruited to postsynaptic
      sites by the A kinase anchor protein AKAP150. We found that LTD was strongly
      impaired in acute hippocampal slices from 2-week-old mice in which the PKA
      binding site on AKAP150 had been genetically deleted (D36 mice). However, basal
      postsynaptic AMPA and NMDA receptor activity was indistinguishable between D36
      and WT mice. During extracellular recordings of field EPSPs and during
      intracellular recording of EPSCs from hippocampal slices from WT mice, H-89 and
      KT5720, two structurally different PKA inhibitors, inhibited LTD by more than 70%
      without affecting basal synaptic transmission or basal phosphorylation of serine
      845 on GluR1. Collectively our data indicate that AKAP150-anchored PKA activity
      is required to induce LTD and not merely to maintain a tonically heightened
      activity level of AMPA receptors as proposed earlier.

PMID- 18617572
TI  - Effect of peers and friends on youth physical activity and motivation to be
      physically active.
AB  - OBJECTIVE: To test whether the presence of a peer or a friend increases the
      motivation to be physically active in overweight and non-overweight youth in a
      laboratory setting. METHODS: Youth motivation to be physically active as a
      function of the social context was measured using a computerized relative
      reinforcing value task to earn points exchangeable for physical and/or sedentary
      activities. RESULTS: The presence of a friend (p<.001) increased youth's;
      motivation to be physically active. The presence of a peer increased overweight
      youth's; motivation to be physically active, whereas this was not the case for
      lean youth (p=.47). Participants biked a greater distance in the presence of a
      friend than when alone (p<.001). Overweight youth biked a greater distance in the
      presence of a peer than when alone, while this was not the case for lean youth
      (p=.23). CONCLUSIONS: Friendships may increase youth's motivation to engage in
      physical activity and promote greater physical activity in non-overweight and
      overweight youth.

PMID- 18617573
TI  - MicroRNA regulation and the variability of human cortical gene expression.
AB  - Understanding the driving forces of gene expression variation within human
      populations will provide important insights into the molecular basis of human
      phenotypic variation. In the genome, the gene expression variability differs
      among genes, and at present, most research has focused on identifying the genetic
      variants responsible for the within population gene expression variation.
      However, little is known about whether microRNAs (miRNAs), which are small
      noncoding RNAs modulating expression of their target genes, could have impact on
      the variability of gene expression. Here we demonstrate that miRNAs likely lead
      to the difference of expression variability among genes. With the use of the
      genome-wide expression data in 193 human brain samples, we show that the
      increased variability of gene expression is concomitant with the increased number
      of the miRNA seeds interacting with the target genes, suggesting a direct
      influence of miRNA on gene expression variability. Compared with the non-miRNA
      target genes, genes targeted by more than two miRNA seeds have increased
      expression variability, independent of the miRNA types. In addition, single
      nucleotide polymorphisms (SNPs) located in the miRNA binding sites could further
      increase the gene expression variability of the target genes. We propose that
      miRNAs are one of the driving forces causing expression variability in the human
      genome.

PMID- 18617574
TI  - Rational vector design and multi-pathway modulation of HEK 293E cells yield
      recombinant antibody titers exceeding 1 g/l by transient transfection under serum
      free conditions.
AB  - Transient transfection allows for fast production of recombinant proteins.
      However, the current bottlenecks in transient transfection are low titers and low
      specific productivity compared to stable cell lines. Here, we report an improved
      transient transfection protocol that yields titers exceeding 1 g/l in HEK293E
      cells. This was achieved by combining a new highly efficient polyethyleneimine
      (PEI)-based transfection protocol, optimized gene expression vectors, use of cell
      cycle regulators p18 and p21, acidic Fibroblast Growth Factor, exposure of cells
      to valproic acid and consequently the maintenance of cells at high cell densities
      (4 million cells/ml). This protocol was reproducibly scaled-up to a working
      volume of 2 l, thus delivering >1 g of purified protein just 2 weeks after
      transfection. This is the fastest approach to gram quantities of protein ever
      reported from cultivated mammalian cells and could initiate, upon further scale
      up, a paradigm shift in industrial production of such proteins for any
      application in biotechnology.

PMID- 18617576
TI  - Recent developments in the perioperative management of adult patients with
      chronic kidney disease.
AB  - The complications of chronic kidney disease (CKD) present the anaesthetist with a
      number of clinical challenges related in part to altered drug handling and to
      difficulties with vascular access and fluid balance. Safe anaesthetic management
      requires an understanding of CKD pathophysiology to prevent aggravation of pre
      existing disease. This review will consider some recent changes in the management
      of adult patients with CKD as they affect the anaesthetist. It will consider
      medical problems associated with CKD together with new developments in
      perioperative management.

PMID- 18617575
TI  - Development of an isoform-specific gene suppression system: the study of the
      human Pax-5B transcriptional element.
AB  - The transcription factor Pax-5, is vital during B lymphocyte differentiation and
      is known to contribute to the oncogenesis of certain cancers. The Pax-5 locus
      generates multiple yet structurally related mRNA transcripts through the specific
      activation of alternative promoter regions and/or alternative splicing events
      which poses challenges in the study of specific isoform function. In this study,
      we investigated the function of a major Pax-5 transcript, Pax-5B using an
      enhanced version of the Hepatitis Delta Virus ribozyme (HDV Rz) suppression
      system that is specifically designed to recognize and cleave the human Pax-5B
      mRNA. The activity of these ribozymes resulted in the specific suppression of the
      Pax-5B transcripts without altering the transcript levels of other closely
      related Pax-5 isoforms mRNAs both in vitro and in an intracellular setting.
      Following stable transfection of the ribozymes into a model B cell line (REH), we
      showed that Pax-5B suppression led to an increase of CD19 mRNA and cell surface
      protein expression. In response to this Pax-5B specific deregulation, a marked
      increase in apoptotic activity compared to control cell lines was observed. These
      results suggest that Pax-5B has distinct roles in physiological processes in cell
      fate events during lymphocyte development.

PMID- 18617577
TI  - Growth hormone excess and the development of growth hormone receptor antagonists.
AB  - In 1990, a single amino acid substitution in the growth hormone (GH) gene at
      position 119 was found to transform the consequent protein from an agonist to an
      antagonist at the growth hormone receptor (GHR). Further amino acid substitutions
      plus prolongation of the half-life of the protein by pegylation resulted in the
      first clinically effective GHR antagonist, pegvisomant. Following extensive
      clinical trials, this medication has emerged as the most efficacious therapy for
      treatment-resistant acromegaly. Subsequent advances in our understanding of GH
      GHR interactions and downstream GH signalling pathways suggest that pegvisomant
      binds to preformed GHR dimers and prevents rotational changes within the receptor
      GH complex necessary for intracellular signalling to occur. This article reviews
      the discovery of pegvisomant, from initial experimental data to successful
      licensing of the drug for treatment-resistant acromegaly, and discusses its other
      potential therapeutic uses in diseases with abnormalities in the GH-IGF-I axis.

PMID- 18617578
TI  - Puckering and blowing facial expressions in people with facial movement
      disorders.
AB  - BACKGROUND AND PURPOSE: People with facial movement disorders are instructed to
      perform various facial movements as part of their physical therapy
      rehabilitation. A difference in the movement of the orbicularis oris muscle has
      been demonstrated among people without facial nerve impairments when instructed
      to "pucker your lips" and to "blow, as if blowing out a candle." The objective of
      this study was to determine whether the within-subject difference between "pucker
      your lips" and "blow, as if blowing out a candle" found in people without facial
      nerve impairments is present in people with facial movement disorders. SUBJECTS
      AND METHODS: People (N=68) with unilateral facial movement disorders were
      observed as they produced puckering and blowing movements. Automated facial image
      analysis of both puckering and blowing was used to determine the difference
      between facial actions for the following movement variables: maximum speed,
      amplitude, duration, and corresponding asymmetry. RESULTS: There was a difference
      between the amplitudes of movement for puckering and blowing. "Blow, as if
      blowing out a candle" produced a larger amplitude of movement. DISCUSSION AND
      CONCLUSION: The findings demonstrate that puckering and blowing movements in
      people with facial movement disorders differ in a manner that is consistent with
      differences found in people who are healthy. This information may be useful in
      the assessment of and intervention for facial movement disorders affecting the
      lower face.

PMID- 18617579
TI  - Scale for contraversive pushing: cutoff scores for diagnosing "pusher behavior"
      and construct validity.
AB  - BACKGROUND AND PURPOSE: Considerable disagreement exists among researchers with
      regard to the prevalence, pathophysiology, and treatment of "pusher behavior"
      (PB), partly because of different testing procedures. This study was primarily
      aimed at establishing cutoff scores for and the construct validity of the Scale
      for Contraversive Pushing (SCP). The prevalence of PB in people with right- and
      left-brain lesions also was investigated. SUBJECTS AND METHODS: The study
      subjects were 105 consecutive patients with recent stroke. Two methods were used
      to diagnose PB: clinical examination and SCP score with 3 different cutoff points
      -an SCP total score of greater than 0 (Crit_1), subscores in each section of the
      scale of greater than 0 (Crit_2), and subscores in each section of the scale of >
      or =1 (Crit_3). Clinical and SCP diagnoses were independently made by different
      examiners. The Cohen kappa coefficient was used to determine the agreement
      between clinical and SCP diagnoses. The construct validity of the SCP was
      estimated by calculation of Spearman rank correlation coefficients for SCP and
      balance, mobility, and functional scores. RESULTS: The agreement between clinical
      and SCP diagnoses was low (kappa=.212) when Crit_1 was used. Crit_2 led to the
      highest agreement with the clinical diagnosis (kappa=.933). However, only Crit_3,
      although globally less accurate (kappa=.754), ensured no false-positive results.
      The construct validity of the SCP was demonstrated by significant (P<.001)
      moderate to high correlations with mobility (rho=.595), functional (rho=.632),
      and balance (rho=.666) scores. The prevalence of PB was not influenced by the
      side of the lesion. A limitation of the study was that the reliability of the
      clinical examination method was not investigated. DISCUSSION AND CONCLUSION: The
      results support the validity of the SCP and suggest the need to choose different
      SCP cutoff criteria (Crit_2 or Crit_3) according to the aim of the evaluation.

PMID- 18617580
TI  - Comparison between immunoturbidimetry, size-exclusion chromatography, and LC-MS
      to quantify urinary albumin.
AB  - BACKGROUND: The accurate and precise measurement of urinary albumin is critical,
      since even minor increases are diagnostically sensitive indicators of renal
      disease, cardiovascular events, and risk for death. To gain insights into
      potential measurement biases, we systematically compared urine albumin
      measurements performed by LC-MS, a clinically available immunoturbidimetric
      assay, and size-exclusion HPLC. METHODS: We obtained unused clinical urine
      samples from 150 patients who were stratified by degrees of albuminuria (<20
      mg/L, 20-250 mg/L, >250 mg/L) as determined by the immunoturbidimetric assay used
      in our clinical laboratory (Roche Hitachi 912). Urine albumin was then remeasured
      via LC-MS and HPLC (Accumin) assays. RESULTS: The immunoturbidimetric assay,
      calibrated using manufacturer-supplied serum-derived calibrators (Diasorin),
      underestimated albumin compared with LC-MS. After calibration with purified HSA,
      this immunoturbidimetric assay correlated well with LC-MS. HPLC overestimated
      albumin compared with both LC-MS and immunoturbidimetry. The current LC-MS and
      HPLC assays both performed poorly at concentrations <20 mg/L. CONCLUSIONS:
      Efforts are needed to establish gold-standard traceable calibrators for clinical
      assays. LC-MS is a specific method to quantify albumin in native urine when
      concentrations exceed 20 mg/L, and therefore could be employed for
      standardization among assays.

PMID- 18617581
TI  - PCR-based analysis of differentially methylated regions of GNAS enables
      convenient diagnostic testing of pseudohypoparathyroidism type Ib.
AB  - BACKGROUND: Pseudohypoparathyroidism type Ib (PHPIb) is characterized by
      parathyroid hormone (PTH) resistance, which can lead to hypocalcemia,
      hyperphosphatemia, and increased serum PTH. The disorder is caused by mutations
      in regulatory regions of the GNAS gene (GNAS complex locus) that lead to
      interferences in the methylation status of alternative GNAS promoters, such as
      exon A/B, NESP55, and XL alpha-s. PHPIb comprises disorders that show distinctive
      changes in methylation status but share the same clinical phenotype: (a) loss of
      methylation only at exon A/B of the GNAS gene and involving no other obvious
      epigenetic abnormalities [e.g., those caused by heterozygous microdeletions in
      the STX16 (syntaxin 16) region and found in many patients with autosomal dominant
      (AD) PHPIb]; (b) methylation abnormalities at several differentially methylated
      regions (DMRs), which are observed in most patients with sporadic PHPIb and some
      families with AD PHPIb. METHODS: To permit early and reliable diagnosis of
      suspected PHPIb, we designed methylation-sensitive restriction enzyme-based and
      bisulfite deamination-based PCR tests for exon A/B and NESP55 DMRs. RESULTS: Both
      PCR strategies permit proper methylation testing of GNAS and NESP55 DMRs and
      elucidate different disease subtypes. We have identified a novel microsatellite
      repeat polymorphism within GNAS exon A/B, and pedigree analyses have shown its
      presence to be conclusive evidence for familial disease. CONCLUSIONS: We provide
      a simple diagnostic test for PHPIb, an imprinting disorder caused by different
      molecular changes within the GNAS complex locus. PHPIb, a complex and
      diagnostically challenging clinical phenotype, can be treated successfully by
      taking steps before the manifestation of symptoms to avoid clinical complications
      in affected patients or asymptomatic members of affected families who show
      positive results in genetic tests.

PMID- 18617582
TI  - Ruptured intracranial aneurysm treatment outcomes.

PMID- 18617583
TI  - Which CT perfusion parameter best reflects cerebrovascular reserve?: correlation
      of acetazolamide-challenged CT perfusion with single-photon emission CT in
      Moyamoya patients.
AB  - BACKGROUND AND PURPOSE: CT perfusion (CTP) is a more readily accessible method
      for evaluation of cerebral perfusion than single-photon emission CT (SPECT). We
      assessed whether there is any resting or drug-challenged CTP parameter
      correlating with cerebrovascular reserve (CVR) obtained by SPECT in Moyamoya
      patients. MATERIALS AND METHODS: Normalized baseline CTP parameters and their
      percentage changes were calculated in 152 regions of interest (ROIs). On
      qualitative SPECT analysis, each ROI was classified in either the "impaired CVR"
      or "normal CVR" group. Quantitative CVR was calculated by using normalized SPECT
      values before and after acetazolamide administration. Baseline CTP parameters and
      their percentage changes were compared with qualitative and quantitative CVRs.
      Receiver operating characteristic (ROC) curve analysis defined the threshold
      values of CTP parameters that best predict impaired qualitative CVR. RESULTS: The
      mean values of CTP parameters were significantly different between normal and
      impaired CVR groups. The percentage change of cerebral blood flow (pcCBF) was
      correlated most significantly with quantitative CVR (r = 0.89; P < .05). The
      correlation coefficients between the baseline CTP parameters and quantitative CVR
      were poor or not significant. The ROC-derived threshold values of pcCBF and mean
      transit time determined impaired CVR with a sensitivity of 94.4 and 85.2;
      specificity of 93.2 and 65.9; positive predictive value of 97.1 and 86.0; and
      negative predictive value of 87.2 and 64.4, respectively. CONCLUSION: Baseline
      CTP parameters are not reliable for predicting impaired CVR. However, pcCBF
      correlated strongly with quantitative CVR; therefore, CTP evaluation for CVR in
      Moyamoya patients requires normalization and acetazolamide challenge.

PMID- 18617584
TI  - What is all of the hype about?

PMID- 18617585
TI  - Prevalence and appearance of the posterior wall defects of the temporal bone
      caused by presumed arachnoid granulations and their clinical significance: CT
      findings.
AB  - BACKGROUND AND PURPOSE: Arachnoid granulations (AGs) of the posterior wall of the
      temporal bone are a rare cause of spontaneous CSF leakage. The purpose of this
      study was to investigate the prevalence and appearance of presumed AGs, evidenced
      by the posterior wall defects of the temporal bone with lobulated or scalloped
      margins on CT scans. MATERIALS AND METHODS: We retrospectively reviewed CT scans
      of the temporal bone obtained in 1255 patients (573 men and 682 women; mean age,
      42 years). We evaluated the prevalence, multiplicity, size, and location of
      presumed AGs in the posterior wall of the temporal bone. Preservation of the
      posterior wall of the mastoid air cells was also investigated and correlated with
      clinical features. RESULTS: Thirty patients (2.4%), including 13 men and 17
      women, aged 27-88 years (mean, 55 years), showed a total of 40 presumed AGs on CT
      scans. Their prevalence tended to increase with age. They were most commonly
      located at the lateral third of the temporal bone at a level of or above the
      common crus. Although 15 lesions in 11 patients also caused focal loss of the
      posterior wall of the mastoid air cells, symptomatic CSF leakage was found in
      only 2 patients, in both of whom the adjacent mastoid air cells were also
      opacified on CT scans. CONCLUSION: Although rare, radiologists need to be
      familiar with the posterior wall defects of the temporal bone caused by presumed
      AGs on CT scans, because they might cause CSF leakage.

PMID- 18617586
TI  - Diffusion tensor imaging characteristics of the corpus callosum in mild,
      moderate, and severe traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: The corpus callosum is an important predilection site for
      traumatic axonal injury but may be unevenly affected in head trauma. We
      hypothesized that there were local differences in axonal injury within the corpus
      callosum as investigated with diffusion tensor imaging (DTI), varying among
      patients with differing severity of traumatic brain injury (TBI). MATERIALS AND
      METHODS: Ethics committee approval and informed consent were obtained. Ten
      control subjects (7 men, 3 women; mean age, 37 +/- 9 years) and 39 patients with
      TBI (27 men, 12 women; 34 +/- 12 years) were investigated, of whom 24 had mild;
      9, moderate; and 6, severe TBI. Regions of interest were selected in the callosal
      genu, body, and splenium to calculate fractional anisotropy (FA), apparent
      diffusion coefficient (ADC), and the number of fibers passing through.
      Statistical comparison was made through analysis of variance with the Scheffe
      post hoc analysis. RESULTS: Compared with controls, patients with mild TBI
      investigated <3 months posttrauma (n = 12) had reduced FA (P < .01) and increased
      ADC (P < .05) in the genu, whereas patients with mild TBI investigated > or =3
      months posttrauma (n = 12) showed no significant differences. Patients with
      moderate and severe TBI, all investigated <3 months posttrauma, had reduced FA (P
      < .001) and increased ADC (P < .01) in the genu compared with controls and
      reduced FA in the splenium (P < .001) without significant ADC change. CONCLUSION:
      Mild TBI is associated with DTI abnormalities in the genu <3 months posttrauma.
      In more severe TBI, both the genu and splenium are affected. DTI suggests a
      larger contribution of vasogenic edema in the genu than in the splenium in TBI.

PMID- 18617587
TI  - Diffuse lipogranulomatosis involving soft tissues of the head and neck due to
      multiple self-injections of mineral oil.
AB  - We describe imaging findings of a 45-year-old man with a 6-month history of
      gradually increasing diffuse swelling of the neck. CT showed diffuse thickening
      and infiltration of the superficial and deep soft tissues bilaterally. On further
      investigation of his history, the patient stated that he had injected mineral oil
      into his neck to clean out his body from drugs. Biopsy results showed
      multinucleated giant cells and inflammatory infiltrates confirming the diagnosis
      of lipogranulomatosis.

PMID- 18617588
TI  - Successful staged endovascular treatment of a symptomatic cervical carotid
      bifurcation stenosis coupled with a coincidental unruptured cerebral aneurysm in
      the carotid distal segment.
AB  - SUMMARY: A 69-year-old woman had a symptomatic cervical carotid stenosis coupled
      with a coincidental unruptured cerebral aneurysm in the carotid distal segment.
      She underwent endovascular coiling for the aneurysm and then carotid stent
      placement (CAS) 1 month later. Both lesions were treated successfully and neither
      complications nor strokes occurred after the procedures. Staged endovascular
      treatment of coiling and subsequent CAS may be safe for patients with a cervical
      carotid stenosis coupled with cerebral aneurysms.

PMID- 18617589
TI  - Cement-embolic stroke associated with vertebroplasty.
AB  - Major neurologic morbidity and mortality with vertebroplasty are rare. We
      describe a 71-year-old woman who had a stroke approximately 30 minutes after
      vertebroplasty. Imaging revealed that bone cement had embolized to the left
      middle cerebral artery. Emergency embolectomy was attempted but was unsuccessful.
      This report emphasizes the need to be aware that intracranial embolization of
      polymethylmethacrylate can occur and describes management strategies to consider.

PMID- 18617590
TI  - Brown-Sequard syndrome secondary to spontaneous bleed from postradiation
      cavernous angiomas.
AB  - SUMMARY: The spontaneous occurrence of acute Brown-Sequard syndrome is an
      extremely rare event, with most reported cases being secondary to spontaneous
      epidural hematomas and spinal cord ischemia. We report a rare case of Brown
      Sequard syndrome from spontaneous intraspinal hemorrhage in a patient with
      multiple cavernous angiomas in the spinal cord secondary to craniospinal
      radiation in childhood. Postulated mechanisms leading to the condition include
      postradiation molecular changes and venous occlusion.

PMID- 18617591
TI  - Intraoperative 3T MR imaging for spinal cord tumor resection: feasibility,
      timing, and image quality using a "twin" MR-operating room suite.
AB  - We assessed feasibility, safety, and timing of an original intraoperative MR
      procedure in 3 cases of resection of spinal cord glioma by using a clinical 3T MR
      system connected to an adjacent operating room in a design being coined "twin" or
      "dual" MR-operating room suite.

PMID- 18617592
TI  - What is the most valid comparison treatment in trials of intrauterine
      insemination, timed or uninfluenced intercourse? A systematic review and meta
      analysis of indirect evidence.
AB  - BACKGROUND: Timed intercourse (TI), which is the usual control treatment in
      trials of intrauterine insemination (IUI), is not a typical coital activity and
      could impair fertility. This review summarizes the trials of IUI of male
      partner's prepared semen among subfertile couples according to whether the
      control group had TI or expectant management. METHODS: A search of relevant
      databases and bibliographies until February 2008 yielded 150 citations of which
      31 were potentially relevant and 11 met all criteria. The total estimates of the
      differences in pregnancy rates per couple were calculated with weights equal to
      the inverse variance. The primary analysis was a categorical meta-analysis by the
      type of control treatment (TI or expectant management). RESULTS: In 11 trials
      with 13 comparisons of IUI and intercourse among 1329 couples with subfertility,
      the average difference in pregnancy rate between IUI and controls was 6.1% in
      trials with TI and 3.9% in trials with expectant management, as the control. The
      adjusted indirect estimate of the difference between the types of control groups
      was 2.8% (95% CI -6.3, 10.7). The difference by type of control treatment was not
      significant, neither in the 11 most relevant trials (P = 0.82), nor in a broader
      group of 19 trials and 2512 patients (P = 0.20). CONCLUSIONS: The additional
      benefit accruing to IUI, where TI is the control, is not significant, but it is
      consistent with the possibility that pregnancy may be less likely in TI controls
      than in expectant management controls.

PMID- 18617593
TI  - Effect of simultaneous morcellation in situ on operative time during laparoscopic
      myomectomy.
AB  - BACKGROUND: Laparoscopic myomectomy (LM) is technically difficult and time
      consuming procedure that requires surgical skill and modifications. The aim of
      this study was to assess factors which affect operative times in LM. METHODS:
      From March 2003 to June 2007, 174 women, who underwent LM for symptomatic myomas,
      were enrolled. Standard LM was performed in the first 4 years and simultaneous
      morcellation in situ (SMI) method was applied in the fifth year. RESULTS: The
      mean myoma weight was 213.5 +/- 190.4 g and the mean operative time was 117.0 +/-
      39.6 min. No laparoconversions occurred and there was a 2.3% rate of
      complications. Total myoma weight increased and operative time declined
      significantly over time. The surgeon's learning curve and the effect of SMI on
      operative time were identified by establishing a nonlinear multiple regression
      model. Model assumptions showed little violation by residual plots. Slopes of the
      average myoma weight (total myoma weight/number of myoma operated) for describing
      the operative time declined along with the study year, suggesting that operative
      experience is a major factor influencing operative time. SMI showed a further 19
      min reduction in the predicted operative time. CONCLUSIONS: Operative time in LM
      is dependent on a multitude of factors including surgical experience. Applying
      SMI during LM is an efficient way to further reduce operative time.

PMID- 18617594
TI  - Fetal cells in the maternal appendix: a marker of inflammation or fetal tissue
      repair?
AB  - BACKGROUND: Fetal microchimeric cells that have trafficked into the maternal
      circulation persist in maternal tissues for years after pregnancy, but their
      biological role is unclear. We investigated whether fetal cells participate in
      maternal tissue repair during human pregnancy. METHODS: Appendix specimens were
      acquired from women undergoing appendicectomy during (n = 8) or after (n = 1)
      pregnancy. Fluorescence in situ hybridization (FISH) determined the presence of
      male presumed-fetal cells, and immunostaining indicated the fetal cell phenotype.
      RESULTS: Male cells were identified in appendiceal tissues from all women with
      known present or past male pregnancies (n = 7) and from a woman with a previous
      spontaneous abortion of undetermined gender (n = 1), but not in one woman with
      three daughters. One woman was only 6 weeks pregnant at appendicectomy. Male
      cells were evenly distributed through appendix tissues, in larger numbers where
      there was a greater degree of inflammation and when the current pregnancy was
      male. Combined immunostaining and Y-FISH demonstrated male desmin+ muscle cells
      and CD3+ lymphocytes, suggesting fetal cells had differentiated. CONCLUSIONS:
      Male-presumed fetal cells of haematopoietic and mesenchymal origin were
      identified in the appendix of all pregnant women who had sons. We suggest that
      fetal cells are present at sites of maternal tissue injury during pregnancy, and
      may participate in tissue repair.

PMID- 18617595
TI  - Nuclear and extranuclear pathway inputs in the regulation of global gene
      expression by estrogen receptors.
AB  - Whereas estrogens exert their effects by binding to nuclear estrogen receptors
      (ERs) and directly altering target gene transcription, they can also initiate
      extranuclear signaling through activation of kinase cascades. We have
      investigated the impact of estrogen-mediated extranuclear-initiated pathways on
      global gene expression by using estrogen-dendrimer conjugates (EDCs), which
      because of their charge and size remain outside the nucleus and can only initiate
      extranuclear signaling. Genome-wide cDNA microarray analysis of MCF-7 breast
      cancer cells identified a subset of 17beta-estradiol (E2)-regulated genes (
      approximately 25%) as EDC responsive. The EDC and E2-elicited increases in gene
      expression were due to increases in gene transcription, as observed in nuclear
      run-on assays and RNA polymerase II recruitment and phosphorylation. Treatment
      with antiestrogen or ERalpha knockdown using small interfering RNA abolished EDC
      mediated gene stimulation, whereas GPR30 knockdown or treatment with a GPR30
      selective ligand was without effect, indicating ER as the mediator of these gene
      regulations. Inhibitors of MAPK kinase and c-Src suppressed both E2 and EDC
      stimulated gene expression. Of note, in chromatin immunoprecipitation assays, EDC
      was unable to recruit ERalpha to estrogen-responsive regions of regulated genes,
      whereas ERalpha recruitment by E2 was very effective. These findings suggest that
      other transcription factors or kinases that are downstream effectors of EDC
      initiated extranuclear signaling cascades are recruited to regulatory regions of
      EDC-responsive genes in order to elicit gene stimulation. This study thus
      highlights the importance of inputs from both nuclear and extranuclear ER
      signaling pathways in regulating patterns of gene expression in breast cancer
      cells.

PMID- 18617596
TI  - The contribution of different androgen receptor domains to receptor dimerization
      and signaling.
AB  - The androgen receptor (AR) is a ligand-activated transcription factor of the
      nuclear receptor superfamily that plays a critical role in male physiology and
      pathology. Activated by binding of the native androgens testosterone and 5alpha
      dihydrotestosterone, the AR regulates transcription of genes involved in the
      development and maintenance of male phenotype and male reproductive function as
      well as other tissues such as bone and muscle. Deregulation of AR signaling can
      cause a diverse range of clinical conditions, including the X-linked androgen
      insensitivity syndrome, a form of motor neuron disease known as Kennedy's
      disease, and male infertility. In addition, there is now compelling evidence that
      the AR is involved in all stages of prostate tumorigenesis including initiation,
      progression, and treatment resistance. To better understand the role of AR
      signaling in the pathogenesis of these conditions, it is important to have a
      comprehensive understanding of the key determinants of AR structure and function.
      Binding of androgens to the AR induces receptor dimerization, facilitating DNA
      binding and the recruitment of cofactors and transcriptional machinery to
      regulate expression of target genes. Various models of dimerization have been
      described for the AR, the most well characterized interaction being DNA-binding
      domain- mediated dimerization, which is essential for the AR to bind DNA and
      regulate transcription. Additional AR interactions with potential to contribute
      to receptor dimerization include the intermolecular interaction between the AR
      amino terminal domain and ligand-binding domain known as the N-terminal/C
      terminal interaction, and ligand-binding domain dimerization. In this review, we
      discuss each form of dimerization utilized by the AR to achieve transcriptional
      competence and highlight that dimerization through multiple domains is necessary
      for optimal AR signaling.

PMID- 18617597
TI  - Glucocorticoid regulation of the promoter of 11beta-hydroxysteroid dehydrogenase
      type 1 is indirect and requires CCAAT/enhancer-binding protein-beta.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert 11keto
      glucocorticoids to active 11beta-hydroxy forms, thereby amplifying intracellular
      glucocorticoid action. Up-regulation of 11beta-HSD1 in adipose tissue and liver
      is of pathogenic importance in metabolic syndrome. However, the mechanisms
      controlling 11beta-HSD1 transcription are poorly understood. Glucocorticoids
      themselves potently increase 11beta-HSD1 expression in many cells, providing a
      potential feed-forward system to pathology. We have investigated the molecular
      mechanisms by which glucocorticoids regulate transcription of 11beta-HSD1,
      exploiting an A549 cell model system in which endogenous 11beta-HSD1 is expressed
      and is induced by dexamethasone. We show that glucocorticoid induction of 11beta
      HSD1 is indirect and requires new protein synthesis. A glucocorticoid-responsive
      region maps to between -196 and -88 with respect to the transcription start site.
      This region contains two binding sites for CCAAT/enhancer-binding protein (C/EBP)
      that together are essential for the glucocorticoid response and that bind
      predominantly C/EBPbeta, with C/EBPdelta present in a minority of the complexes.
      Both C/EBPbeta and C/EBPdelta are rapidly induced by glucocorticoids in A549
      cells, but small interfering RNA-mediated knockdown shows that only C/EBPbeta
      reduction attenuates the glucocorticoid induction of 11beta-HSD1. Chromatin
      immunoprecipitation studies demonstrated increased binding of C/EBPbeta to the
      11beta-HSD1 promoter in A549 cells after glucocorticoid treatment. A similar
      mechanism may apply in adipose tissue in vivo where increased C/EBPbeta mRNA
      levels after glucocorticoid treatment were associated with increased 11beta-HSD1
      expression. C/EBPbeta is a key mediator of metabolic and inflammatory signaling.
      Positive regulation of 11beta-HSD1 by C/EBPbeta may link amplification of
      glucocorticoid action with metabolic and inflammatory pathways and may represent
      an endogenous innate host-defense mechanism.

PMID- 18617598
TI  - British American Tobacco and the "insidious impact of illicit trade" in
      cigarettes across Africa.
AB  - OBJECTIVES: To provide an overview of the complicity of British American Tobacco
      (BAT) in the illicit trade of cigarettes across the African continent in terms of
      rationale, supply routes and scale. METHODS: Analysis of internal BAT documents
      and industry publications. RESULTS: BAT has relied on illegal channels to supply
      markets across Africa since the 1980s. Available documents suggest smuggling has
      been an important component of BAT's market entry strategy in order to gain
      leverage in negotiating with governments for tax concessions, compete with other
      transnational tobacco companies, circumvent local import restrictions and
      unstable political and economic conditions and gain a market presence. BAT worked
      through distributors and local agents to exploit weak government capacity to gain
      substantial market share in major countries. CONCLUSIONS: Documents demonstrate
      that the complicity of BAT in cigarette smuggling extends to Africa, which
      includes many of the poorest countries in the world. This is in direct conflict
      with offers by the company to contribute to stronger international cooperation to
      tackle the illicit tobacco trade.

PMID- 18617599
TI  - Health-related quality of life of long-term high-grade glioma survivors.
AB  - The objective of this study was to compare the health-related quality of life
      (HRQOL) of long-term to short-term high-grade glioma (HGG) survivors, determine
      the prognostic value of HRQOL for overall survival, and determine the effect of
      tumor recurrence on HRQOL for long-term survivors. Following baseline assessment
      (after surgery, before radiotherapy), self-perceived HRQOL (using the Medical
      Outcomes Study Short Form 36 [SF-36]) and brain tumor-specific symptoms (using
      the 20-item Brain Cancer Module) were assessed every 4 months until 16 months
      after histological diagnosis. Kaplan-Meier survival analysis and the Cox
      proportional hazards model were performed to estimate overall survival of
      patients with impaired scores on the aggregated SF-36 higher-order summary scores
      measuring physical functioning on a physical component scale and on a mental
      component scale (MCS). Sixteen patients with a short-term survival (baseline and
      4-month follow-up) and 16 with a long-term survival (follow-up until 16 months
      after diagnosis) were selected out of 68 initially recruited HGG patients. At
      baseline, the short-term and long-term survivors did not differ in their HRQOL.
      Between baseline and the 4-month follow-up, HRQOL of short-term survivors
      deteriorated, whereas the long-term survivors improved to a level comparable to
      healthy controls. Patients with impaired mental functioning (MCS) at baseline had
      a shorter median survival than patients with normal functioning. After accounting
      for differences in patient and tumor characteristics, however, mental functioning
      was not independently related to poorer overall survival. Not surprisingly, in
      the group of long-term survivors, the five patients with recurrence had a more
      compromised HRQOL at the 16-month follow-up compared to the 11 patients without
      recurrence. We concluded that baseline HRQOL is not related to duration of
      survival and that long-term survivors show improvement of HRQOL to a level
      comparable to that of the healthy.

PMID- 18617600
TI  - Suppression of CYP2B induction by alendronate-mediated farnesyl diphosphate
      synthase inhibition in primary cultured rat hepatocytes.
AB  - We previously reported that squalestatin 1-mediated induction of CYP2B expression
      is attributable to squalene synthase inhibition and accumulation of an endogenous
      isoprenoid(s) that is capable of activating the constitutive androstane receptor.
      To determine whether squalestatin 1-mediated CYP2B induction is strictly
      dependent on the biosynthesis of farnesyl pyrophosphate (FPP), the substrate for
      squalene synthase, the effects of alendronate, a nitrogen-containing
      bisphosphonate inhibitor of farnesyl diphosphate synthase, on basal, squalestatin
      1-inducible, and phenobarbital-inducible CYP2B expression in primary cultured rat
      hepatocytes were assessed. Alendronate treatment alone had no effect on CYP2B or
      CYP3A mRNA expression in the hepatocyte cultures, but alendronate cotreatment
      completely suppressed squalestatin 1-mediated CYP2B mRNA induction at
      concentrations (60 and 100 microM) that effectively inhibited cellular farnesyl
      diphosphate synthase activity, as assessed by reductions of squalestatin 1
      mediated FPP accumulation, and that were not toxic to the cells, as indicated by
      a lack of effect on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide
      activity. Alendronate cotreatment also partially suppressed phenobarbital
      inducible CYP2B expression, and this suppressive effect was attenuated by
      additional cotreatment with the upstream pathway inhibitor, pravastatin. These
      findings not only demonstrate that squalestatin 1-mediated CYP2B induction cannot
      occur in the absence of FPP biosynthesis but also indicate that one or more
      upstream isoprenoids, possibly isopentenyl pyrophosphate and/or dimethylallyl
      pyrophosphate, function to antagonize the CYP2B induction process.

PMID- 18617601
TI  - Involvement of multiple transporters in the hepatobiliary transport of
      rosuvastatin.
AB  - Rosuvastatin is an HMG-CoA reductase inhibitor and one of the most hydrophilic
      among the commercially available statins. It is efficiently accumulated in the
      liver and excreted into the bile in an unchanged form in rats, suggesting that
      hepatic transporters play a major role in its clearance. Therefore, we
      investigated the transporters responsible for the hepatic uptake and biliary
      excretion of rosuvastatin. Uptake studies revealed that human organic anion
      transporting polypeptide (OATP) 1B1, OATP1B3, and OATP2B1 accept rosuvastatin as
      a substrate. Among the OATP family transporters, OATP1B1 contributes
      predominantly to the hepatic uptake of rosuvastatin, as estimated with the
      previously published relative activity factor method, and OATP1B3 is also partly
      involved. Significant vectorial basal-to-apical transport was observed in
      OATP1B1/multidrug resistance-associated protein 2 (MRP2), OATP1B1/multidrug
      resistance protein 1 (MDR1), and OATP1B1/breast cancer resistance protein (BCRP)
      double transfectants compared with that in an OATP1B1 single transfectant or in
      vector-transfected control cells. The ATP-dependent uptake of rosuvastatin by
      human BCRP-expressing membrane vesicles was significantly higher than the uptake
      by green fluorescent protein-expressing control vesicles, suggesting that MRP2,
      MDR1, and BCRP can transport rosuvastatin. Under in vivo conditions, the biliary
      excretion clearances based on the intrahepatic concentration of the parent
      rosuvastatin in Eisai hyperbilirubinemic rats and Bcrp1 knockout mice were
      reduced to 53% and 12% of those in the control Sprague-Dawley rats and FVB mice,
      respectively, indicating that rat Mrp2 and mouse Bcrp1 are both partly involved
      in the biliary excretion of rosuvastatin. These results suggest that multiple
      transporters are involved in the hepatic uptake and efflux of rosuvastatin.

PMID- 18617602
TI  - Metabolic activity of cytochrome p450 isoforms in hepatocytes cryopreserved with
      wheat protein extract.
AB  - The drug discovery and development process requires adequate safety testing for
      drug toxicity before new drugs can be administered to patients. Hepatocytes are
      used in vitro to screen compounds for hepatotoxicity, induction of drug
      metabolizing enzymes such as cytochrome P450 (P450) isoforms, drug-drug
      interactions, and establish human relevance for metabolism. Cryopreservation
      makes it possible to preserve a large quantity of functional hepatocytes.
      Techniques for cryopreservation of hepatocytes are mainly based on dimethyl
      sulfoxide (DMSO). However, analyses of metabolic capacities of cryopreserved
      hepatocytes are often limited by loss of functional integrity of hepatocytes
      after thawing. Therefore, it is necessary to improve techniques of
      cryopreservation. We have developed a new cryopreservation technology for
      mammalian cells based on a wheat protein extract (WPE). We determined whether the
      WPE can better preserve activities of major P450 isoforms both in suspension and
      monolayer cultures of hepatocytes. This was achieved by comparing basal and
      inducible or metabolic activities of isoforms CYP1A1, CYP1A2, CYP2C6, CYP2D2, and
      CYP3A in rat hepatocytes that were cryopreserved with WPE, relative to fresh
      cells and those cryopreserved with DMSO. We conclusively show that rat
      hepatocytes cryopreserved with WPE retain their metabolic competency and their
      ability to respond to classical P450 inducers when compared with freshly isolated
      hepatocytes. These findings clearly show that WPEs are an excellent
      cryopreservant for rat hepatocytes. They are an efficient, nontoxic, economic
      natural product and universal cryoprotectant that is superior to DMSO, which has
      limitations because of cellular toxicity.

PMID- 18617603
TI  - Pharmacokinetics of the novel nicotinic receptor antagonist N,N'-dodecane-1,12
      diyl-bis-3-picolinium dibromide in the rat.
AB  - Plasma and brain concentrations of the nicotinic acetylcholine receptor
      antagonist and blood-brain barrier choline transporter substrate, N,N'-dodecane
      1,12-diyl-bis-3-picolinium dibromide (bPiDDB), were analyzed by liquid beta
      scintillation spectrometry after administration of [14CH3]bPiDDB to male Sprague
      Dawley rats. Plasma concentrations of [14CH3]bPiDDB were determined at 10 time
      points over 3 h. Absolute plasma bioavailabilities (1, 3, and 5.6 mg/kg s.c.)
      were 80.3, 68.2, and 103.7%, respectively. bPiDDB (1, 3, and 5.6 mg/kg) gave Cmax
      values of 0.13, 0.33, and 0.43 microg/ml, respectively, Tmax values of 5.0, 6.7,
      and 8.8 min, respectively, and t1/2 values of 76.0, 54.6, and 41.7 min,
      respectively. Mean area under the plasma concentration versus time curve from
      time zero to infinity (micrograms per minute per milliliter) and mean Cmax
      (microg/ml) values were dose-dependent (r2=0.9361 and 0.7968, respectively) over
      the dose range studied. No metabolism of [14CH3]bPiDDB was detected with any dose
      of bPiDDB administered. Only moderate protein binding (63-65% in plasma and 59
      62% in brain supernatant) was observed, which was reversible. Brain
      concentrations and brain/plasma ratios of bPiDDB after a single 5.6 mg/kg s.c.
      dose over 5 to 60 min ranged from 0.09 to 0.33 microg/g brain tissue and were
      maximal at 10 min after injection, representing approximately 0.6% of the
      administered dose. Brain/blood ratio (0.18 at 5 min to 0.51 at 60 min after
      injection) was observed, indicating that clearance from brain is slower than
      clearance from plasma. The results show that bPiDDB is distributed rapidly from
      the site of injection into plasma, affords good plasma concentrations, and
      appears to reach brain tissues via facilitated transport by the blood-brain
      barrier choline transporter to afford therapeutically relevant concentrations in
      rat brain.

PMID- 18617604
TI  - Stereoselective first-pass metabolism of verapamil in the small intestine and
      liver in rats.
AB  - Verapamil (VP) is used as a racemate but shows stereoselective pharmacokinetics
      and pharmacodynamics. It undergoes extensive first-pass metabolism.
      Stereoselective first-pass metabolism in the intestine and liver was investigated
      in vivo and in vitro to determine its impact on the disposition of VP and its
      main metabolite, norverapamil (NVP). VP racemate was administered to rats i.v.,
      p.o., and via the portal vein. The formation rates of the main metabolites of the
      VP enantiomers were estimated in an in vitro intestinal microsomal study. The
      hepatic bioavailability of VP showed saturable metabolism, and the hepatic
      bioavailability of R-VP was higher than that of S-VP. Conversely, the intestinal
      bioavailability of R-VP was lower than that of S-VP, resulting in a higher
      systemic bioavailability of S-VP. The pharmacokinetics of the NVP enantiomers was
      similar. These results suggest that the stereoselectivity of the total
      bioavailability of VP is determined by first-pass metabolism in the small
      intestine and liver, and that the NVP enantiomers observed in the systemic
      circulation after p.o. administration of VP racemate originate mainly from the
      liver in rats.

PMID- 18617605
TI  - Higher physical activity is associated with increased androgens, low interleukin
      6 and less aortic calcification in peripheral obese elderly women.
AB  - The presence of peripheral fat mass (PFM) appears to counteract the atherogenic
      trends of central fat mass through mechanisms presently poorly understood. In
      elderly women with distinct forms of body fat distribution, we wanted to study
      whether physical activity and aortic calcification are related to plasma levels
      of cortisol, 17-alpha-hydroxyprogesterone (17-alpha-OHP), dehydroepiandrosterone
      (DHEA), androstenedione (ASD), and interleukin 6 (IL6) accomplishing an anti
      atherogenic milieu. A total of 276 well-defined generally healthy women aged 60
      85 years were included. Categorization of body fat distribution was based on the
      relative presence of central to PFM measured by dual-energy X-ray absorptiometry.
      Women meticulously reported weekly physical activity. Outcome measures were
      aortic calcification between lumbar vertebra L1 and L4, plasma levels of
      hormones, and IL6. In peripheral adipose women, plasma DHEA and ASD increased
      with the degree of physical activity. This was also mirrored in the ratios of
      cortisol/DHEA and cortisol/17-alpha-OHP. Peripheral adipose women with high DHEA
      relative to cortisol had less severe aortic calcification, and in the same group
      a higher level of physical activity was associated with lower levels of plasma
      IL6. In conclusion, this study demonstrates that high physical activity is
      associated with a high circulating androgen to cortisol ratio, low IL6, and less
      severe aortic calcification. Since androgens inhibit IL6 secretion, the activity
      induced increase of these hormones might be an anti-atherogenic signal.

PMID- 18617606
TI  - Differentiation and proliferation of periosteal osteoblast progenitors are
      differentially regulated by estrogens and intermittent parathyroid hormone
      administration.
AB  - The periosteum is now widely recognized as a homeostatic and therapeutic target
      for actions of sex steroids and intermittent PTH administration. The mechanisms
      by which estrogens suppress but PTH promotes periosteal expansion are not known.
      In this report, we show that intermittent PTH(1-34) promotes differentiation of
      periosteal osteoblast precursors as evidenced by the stimulation of the
      expression or activity of alkaline phosphatase as well as of targets of the bone
      morphogenetic protein 2 (BMP-2) and Wnt pathways. In contrast, 17beta-estradiol
      (E2) had no effect by itself. However, it attenuated PTH- or BMP-2-induced
      differentiation of primary periosteal osteoblast progenitors. Administration of
      intermittent PTH to ovariectomized mice induced rapid phosphorylation of the BMP
      2 target Smad1/5/8 in the periosteum. A replacement dose of E2 had no effect by
      itself but suppressed PTH-induced phosphorylation of Smad1/5/8. In contrast to
      its effects to stimulate periosteal osteoblast differentiation, PTH promoted and
      subsequently suppressed proliferation of periosteal osteoblast progenitors in
      vitro and in vivo. E2 promoted proliferation and attenuated the antiproliferative
      effect of PTH. Both hormones protected periosteal osteoblasts from apoptosis
      induced by various proapoptotic agents. These observations suggest that the
      different effects of PTH and estrogens on the periosteum result from opposing
      actions on the recruitment of early periosteal osteoblast progenitors.
      Intermittent PTH promotes osteoblast differentiation from periosteum-derived
      mesenchymal progenitors through ERK-, BMP-, and Wnt-dependent signaling pathways.
      Estrogens promote proliferation of early osteoblast progenitors but inhibit their
      differentiation by osteogenic agents such as PTH or BMP-2.

PMID- 18617607
TI  - Nonclassical mechanisms of progesterone action in the brain: II. Role of
      calmodulin-dependent protein kinase II in progesterone-mediated signaling in the
      hypothalamus of female rats.
AB  - In addition to the activation of classical progestin receptor-dependent genomic
      pathway, progesterone (P) can activate nonclassical, membrane-initiated signaling
      pathways in the brain. We recently demonstrated rapid P activation of second
      messenger kinases, protein kinase A, and protein kinase C in the ventromedial
      nucleus (VMN) and preoptic area (POA) of rat brain. To determine whether P can
      activate yet another Ca+2 dependent kinase, we examined the rapid P modulation of
      calcium and calmodulin-dependent protein kinase II (CaMKII) in the VMN and POA in
      female rats. A rapid P-initiated activation of CaMKII basal activity was observed
      in the VMN but not the POA at 30 min. Estradiol benzoate (EB) priming enhanced
      this CaMKII basal activity in both the VMN and POA. CaMKII protein levels and
      phosphorylation of Thr-286 moiety on CaMKII, however, remained unchanged with EB
      and/or P treatments, suggesting that the changes in the CaMKII kinase activity
      are due to rapid P modulation of the kinase activity and not its synthesis or
      autoactivation. Furthermore, intracerebroventricular (icv) administration of a
      CaMKII-specific inhibitor, KN-93, 30 min prior to the P infusion, in EB-primed,
      ovariectomized female rats inhibited CaMKII activation but not protein kinase A
      and protein kinase C activities. Interestingly, icv administration of KN-93 30
      min prior to P infusion (icv) resulted in a reduction but not total inhibition of
      P-facilitated lordosis response in EB-primed female rats. These observations
      suggest a redundancy or, alternately, a hierarchy in the P-regulated activation
      of kinase signaling cascades in female reproductive behavior.

PMID- 18617608
TI  - Nonclassical mechanisms of progesterone action in the brain: I. Protein kinase C
      activation in the hypothalamus of female rats.
AB  - The modulation of gene regulation by progesterone (P) and its classical
      intracellular regulation by progestin receptors in the brain, resulting in
      alterations in physiology and behavior has been well studied. The mechanisms
      mediating the short latency effects of P are less well understood. Recent studies
      have revealed rapid nonclassical signaling action of P involving the activation
      of intracellular signaling pathways. We explored the involvement of protein
      kinase C (PKC) in P-induced rapid signaling in the ventromedial nucleus of the
      hypothalamus (VMN) and preoptic area (POA) of the rat brain. Both the Ca2+
      independent (basal) PKC activity representing the activation of PKC by the in
      vivo treatments and the Ca+2-dependent (total) PKC activity assayed in the
      presence of exogenous cofactors in vitro were determined. A comparison of the two
      activities demonstrated the strength and temporal status of PKC regulation by
      steroid hormones in vivo. P treatment resulted in a rapid increase in basal PKC
      activity in the VMN but not the POA. Estradiol benzoate priming augmented P
      initiated increase in PKC basal activity in both the VMN and POA. These increases
      were inhibited by intracerebroventricular administration of a PKC inhibitor
      administered 30 min prior to P. The total PKC activity remained unchanged
      demonstrating maximal PKC activation within 30 min in the VMN. In contrast, P
      regulation in the POA significantly attenuated total PKC activity +/- estradiol
      benzoate priming. These rapid changes in P-initiated PKC activity were not due to
      changes in PKC protein levels or phosphorylation status.

PMID- 18617610
TI  - Amino acid-modified calcitonin immunization induces tumor epitope-specific
      immunity in a transgenic mouse model for medullary thyroid carcinoma.
AB  - Up to now, no relevant tumor antigen has been identified in medullary thyroid
      carcinoma (MTC). The aim of the present study was to prove the concept of an
      immunization with an amino acid-modified calcitonin (CT) for the treatment of MTC
      in a transgenic mouse model. Amino acid-modified (human) CT has been chosen for
      vaccination because of its higher binding affinity to the murine H2-Kb-MHC
      molecule. Mice were immunized over 6 months with monthly injections of amino acid
      modified CT-pulsed dendritic cells. For enumeration of tumor epitope-specific
      CD8+ cytotoxic T cells, tetramer analyses were performed. CT peptide-treated mice
      revealed a mean 0.73 +/- 0.45 and 0.91 +/- 0.59% positive cells, depending on the
      two tetramers tested, whereas no increase was seen in control protein-immunized
      mice (0.08-0.12% tetramer-positive cells). Importantly, the subset of CT-specific
      CD8+ T cells also showed a high expression of interferon-gamma. In line with
      these results, CT-immunized mice also showed an intratumor infiltration with CD8+
      T lymphocytes. Importantly, we also found a diminished tumor outgrowth of -57%
      and a decrease of the serum CT levels (2.0 +/- 0.1 pg/ml) compared with control
      protein-immunized Ret/Cal mice (3.0 +/- 0.4 pg/ml). In summary, we show that
      amino acid-modified CT is recognized from the immune system leading to a specific
      antitumor immune response and a diminished tumor outgrowth in transgenic MTC
      mice. The results are of potential importance because they might be applicable to
      patients with metastatic spread of a MTC.

PMID- 18617609
TI  - The role of the forebrain glucocorticoid receptor in acute and chronic stress.
AB  - Previous work has implicated the forebrain glucocorticoid receptor (GR) in
      feedback regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. The
      present series of experiments used male mice with a targeted forebrain-specific
      GR knockout (in which forebrain includes the prefrontal cortex, hippocampus, and
      basolateral amygdala) to determine the role of forebrain GR in HPA axis
      regulation after stress. The data indicate that the forebrain GR is necessary for
      maintaining basal regulation of corticosterone secretion in the morning,
      confirming its role in HPA axis regulation. Our data further indicate that the
      forebrain GR is necessary for negative feedback after both mild and robust acute
      psychogenic stressors but not hypoxia, a systemic stressor. In contrast,
      forebrain-specific GR knockout and control mice exhibit equivalent HPA axis
      hyperactivity and facilitation after chronic variable stress, suggesting that
      changes in forebrain GR are not essential for chronic stress-induced pathology.
      These studies provide novel and definitive evidence that the forebrain GR
      selectively contributes negative feedback regulation of HPA axis responses to
      psychogenic stressors. Moreover, the data indicate that chronic stress-induced
      alterations in HPA axis function are mediated by mechanisms independent of the
      forebrain GR. Overall, the data are consistent with an essential role of the
      forebrain GR in coordinating endocrine responses to stimuli of a psychological
      origin.

PMID- 18617611
TI  - Systematic expression analysis and antibody screening do not support the
      existence of naturally occurring progesterone receptor (PR)-C, PR-M, or other
      truncated PR isoforms.
AB  - Functional progesterone withdrawal associated with human parturition has been
      ascribed to various mechanisms modulating the function of the classical
      progesterone receptors (PRs), B and A, in utero. These include up-regulation of
      the inhibitory PR-C isoform, described as a 60-kDa protein occurring from
      translation initiation at codon 595. Our initial attempts to detect PR-C yielded
      uninterpretable results. To systematically validate antibodies for
      immunodetection of PR isoforms, we generated expression vectors for PR variants
      originating from putative start codons AUG-289, -301, -595, -632, and -692 in
      addition to those for PR-B and PR-A, and for alternative splice variants PR-T, PR
      S, and PR-M. All constructs were subjected to in vitro and in vivo translation
      and immunoblotting with a panel of 13 PR antibodies. Antibodies raised against
      full-length PR were generally not capable of detecting N-terminally truncated
      forms, whereas C-terminal antibodies did not or only weakly reacted with PR-B and
      PR-A but produced prominent nonspecific signals. Thus, immunodetection of N
      terminally truncated PR isoforms is prone to artifacts. Proteins of about 64 kDa
      were expressed from PR-289 and -301, but no corresponding endogenous forms were
      observed. PR-T, PR-S, and PR-M cDNAs yielded no detectable translation products.
      No protein was translated from AUG-595 in our PR-C expression vector unless a
      Kozak sequence was introduced, and the product was not 60 but 38 kDa in size.
      Thus, the 60-kDa protein called PR-C does not originate from AUG-595 and is not a
      naturally occurring PR isoform.

PMID- 18617613
TI  - Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative
      of a hypophysiotropic role in the negative regulation of gonadotropin secretion.
AB  - We identified a gene in the ovine hypothalamus encoding for RFamide-related
      peptide-3 (RFRP-3), and tested the hypothesis that this system produces a
      hypophysiotropic hormone that inhibits the function of pituitary gonadotropes.
      The RFRP-3 gene encodes for a peptide that appears identical to human RFRP-3
      homolog. Using an antiserum raised against RFRP-3, cells were localized to the
      dorsomedial hypothalamic nucleus/paraventricular nucleus of the ovine brain and
      shown to project to the neurosecretory zone of the ovine median eminence,
      predicating a role for this peptide in the regulation of anterior pituitary gland
      function. Ovine RFRP-3 peptide was tested for biological activity in vitro and in
      vivo, and was shown to reduce LH and FSH secretion in a specific manner. RFRP-3
      potently inhibited GnRH-stimulated mobilization of intracellular calcium in
      gonadotropes. These data indicate that RFRP-3 is a specific and potent mammalian
      gonadotropin-inhibiting hormone, and that it acts upon pituitary gonadotropes to
      reduce GnRH-stimulated gonadotropin secretion.

PMID- 18617612
TI  - Variation in kisspeptin and RFamide-related peptide (RFRP) expression and
      terminal connections to gonadotropin-releasing hormone neurons in the brain: a
      novel medium for seasonal breeding in the sheep.
AB  - Reproductive activity in sheep is seasonal, being activated by short-day
      photoperiods and inhibited by long days. During the nonbreeding season, GnRH
      secretion is reduced by both steroid-independent and steroid-dependent (increased
      response to estradiol negative feedback) effects of photoperiod. Kisspeptin (also
      known as metastin) and gonadotropin-inhibitory hormone (GnIH, or RFRP) are two
      RFamide neuropeptides that appear critical in the regulation of the reproductive
      neuroendocrine axis. We hypothesized that expression of kisspeptin and/or RFRP
      underlies the seasonal change in GnRH secretion. We examined kisspeptin and RFRP
      (protein and mRNA) expression in the brains of ovariectomized (OVX) ewes treated
      with estradiol (OVX+E) during the nonbreeding and breeding seasons. In OVX+E
      ewes, greater expression of kisspeptin and Kiss1 mRNA in the arcuate nucleus and
      lesser expression of RFRP (protein) in the dorsomedial nucleus of the
      hypothalamus were concurrent with the breeding season. There was also a greater
      number of kisspeptin terminal contacts onto GnRH neurons and less RFRP-GnRH
      contacts during the breeding season (compared with the nonbreeding season) in
      OVX+E ewes. Comparison of OVX and OVX+E ewes in the breeding and nonbreeding
      season revealed a greater effect of steroid replacement on inhibition of
      kisspeptin protein and Kiss1 mRNA expression during the nonbreeding season.
      Overall, we propose that the two RFamide peptides, kisspeptin and RFRP, act in
      concert, with opposing effects, to regulate the activity of GnRH neurons across
      the seasons, leading to the annual change in fertility and the cyclical seasonal
      transition from nonbreeding to breeding season.

PMID- 18617614
TI  - Insulin stimulates interleukin-6 expression and release in LS14 human adipocytes
      through multiple signaling pathways.
AB  - IL-6 is an important cytokine that regulates both immune and metabolic functions.
      Within adipose tissue, preadipocytes produce significant amounts of IL-6, but
      little is known about the factors or mechanisms that regulate IL-6 production in
      these cells. Using LS14, a newly developed human adipocyte cell line, our
      objective was to determine the mechanisms by which insulin stimulates IL-6
      production and release in preadipocytes. Insulin increased IL-6 gene expression
      and secretion in a time- and dose-dependent manner. Insulin decreased cyclic AMP
      (cAMP) but increased cyclic GMP (cGMP) levels, and IL-6 expression/release was
      stimulated by a cGMP analog. The stimulatory effect of insulin and cGMP was
      abrogated by a specific inhibitor of protein kinase G (cyclic GMP-dependent
      protein kinase). Both insulin and cGMP rapidly induced phosphorylation of cAMP
      response element binding protein. Insulin also activated the MAPK signaling
      pathway, and its blockade prevented the insulin-stimulated increases in IL-6 cell
      content and release, but not IL-6 gene expression. Although inhibition of the
      proteosome increased IL-6 cell content and release, proteosome activity was
      unaffected by insulin. These data suggest that the stimulatory effects of insulin
      on IL-6 release involve several interrelated components: transcription,
      intracellular releasable pool, and secretion, which are differentially regulated
      and, thus, determine the size of the releasable pool of IL-6. Insulin-induced IL
      6 gene expression is mediated by cGMP/cyclic GMP-dependent protein kinase/cAMP
      response element binding protein, whereas MAPK is involved in the insulin
      stimulated IL-6 synthesis/release.

PMID- 18617616
TI  - Transgenic mice overexpressing growth hormone (GH) have reduced or increased
      cardiac apoptosis through activation of multiple GH-dependent or -independent
      cell death pathways.
AB  - GH has antiapoptotic effects in cardiac or noncardiac cell lines; however,
      increased apoptosis has been found in myocardial samples of patients with
      acromegaly. The aim of this study was to investigate cardiac apoptosis and
      underlying molecular mechanisms in transgenic mice overexpressing bovine GH
      [acromegalic mice (Acro)] aged 3 or 9 months. Cardiomyocyte apoptosis was
      evaluated by terminal deoxynucleotidyl transferase assay and annexin V;
      expression of pro- or antiapoptotic proteins was assessed by Western blot.
      Specificity of GH action was confirmed using a selective GH receptor antagonist.
      Apoptosis was lower in 3-month-old Acro than in controls; reduction was abolished
      by a GH receptor antagonist. The effects of GH were consistent with an
      antiapoptotic phenotype (increased Bcl2 and Bcl-XL and reduced Bad and cytochrome
      c levels, leading to lower activation of caspase-9 and caspase-3). In contrast,
      apoptosis was higher in 9-month-old Acro than in littermate controls; in
      addition, a GH receptor antagonist was without effect; the proapoptotic phenotype
      consisted in increased Bad, cytochrome c, caspase-9, and caspase-3. GH reduced
      apoptosis through p38 and p44/42 kinase pathways at young ages, whereas
      phosphatidylinositol-3-kinase was silent; on the contrary, the effects of GH on
      p38 and p44/42 kinase pathways were overcome by GH-independent stimuli in 9-month
      old Acro. In addition, the antiapoptotic effect of GH was still present at this
      age as shown by phosphatidylinositol-3-kinase/Akt pathway activation. In
      conclusion, chronic GH excess reduced apoptosis at a young age, whereas its
      antiapoptotic action was overwhelmed in older animals by GH-independent
      mechanisms, leading to increased cell death.

PMID- 18617615
TI  - Critical roles for fast synaptic transmission in mediating estradiol negative and
      positive feedback in the neural control of ovulation.
AB  - A switch in the balance of estradiol feedback actions from negative to positive
      initiates the GnRH surge, triggering the LH surge that causes ovulation. Using an
      ovariectomized, estradiol-treated (OVX+E) mouse model that exhibits daily
      switches between negative in the morning and positive feedback in the evening, we
      investigated the roles of fast synaptic transmission in regulating GnRH neuron
      firing during negative and positive feedback. Targeted extracellular recordings
      were used to monitor activity of GnRH neurons from OVX+E and OVX mice in control
      solution or solution with antagonists to both ionotropic glutamate and gamma
      aminobutyric acid receptors (blockade). Blockade had no effect on activity of OVX
      cells. In contrast, in OVX+E cells in the morning, blockade increased activity
      compared with control cells, whereas in the evening, blockade decreased activity.
      In vivo barbiturate sedation of OVX+E mice that blocked LH surge induction
      prevented the in vitro evening changes in firing rate and response to blockade.
      These observations suggest at least partial inversion of the negative-to-positive
      switch in estradiol feedback action and indicate that changes in fast synaptic
      transmission to GnRH neurons and within the network of cells presynaptic to GnRH
      neurons are critical for mediating estradiol negative and positive feedback
      actions on GnRH neurons. Fast synaptic transmission may also affect GnRH neuron
      activity indirectly through altering release of excitatory and inhibitory
      neuromodulators onto GnRH neurons at specific times of day. Fast synaptic
      transmission is thus critical for proper generation and timing of the GnRH surge.

PMID- 18617617
TI  - Lysophosphatidic acid mediates interleukin-8 expression in human endometrial
      stromal cells through its receptor and nuclear factor-kappaB-dependent pathway: a
      possible role in angiogenesis of endometrium and placenta.
AB  - Lysophosphatidic acid (LPA) is a pleiotropic phospholipid molecule involved in
      inflammation, angiogenesis, would healing, and cancer invasion. Whereas serum
      lysophospholipase D activity increases in women with pregnancy, the role of LPA
      in pregnancy remains unclear. We investigated the expression of LPA receptors and
      function of LPA in endometrial stromal cells. Histologically normal endometrium
      was obtained from surgical specimens of women undergoing hysterectomy for
      leiomyoma. First-trimester decidua was obtained from women receiving elective
      termination of pregnancy. We examined the expressions of LPA1, LPA2, and LPA3
      receptors in endometrial stromal cells. The effects of LPA on the expression of
      vascular endothelial growth factor, IL-6, and IL-8 were examined. Signal pathways
      of LPA were delineated. Functions of secretory angiogenic factors were tested
      using human endometrial microvascular endothelial cells. Immunoreactivity and
      mRNA of LPA1 receptors were identified in endometrial stromal cells. LPA enhanced
      IL-8 expression in a dose- and time-dependent manner, whereas vascular
      endothelial growth factor or IL-6 expression was not affected by LPA treatment.
      Mechanistic dissection disclosed that LPA functioned via the Gi protein, MAPK/p38
      and nuclear factor-kappaB pathway. LPA-induced IL-8 enhanced migration,
      permeability, capillary tube formation, and proliferation of human endometrial
      microvascular endothelial cells. Endometrial stromal cells express LPA1
      receptors. Through the LPA1 receptor, LPA induces IL-8 expression via a nuclear
      factor-kappaB-dependent signal pathway. These results could suggest that LPA may
      play a role in angiogenesis of endometrium and placenta through induction of IL-8
      in endometrial stromal cells during pregnancy.

PMID- 18617618
TI  - 17beta-estradiol activates estrogen receptor beta-signalling and inhibits
      transient receptor potential vanilloid receptor 1 activation by capsaicin in
      adult rat nociceptor neurons.
AB  - There is mounting evidence that estrogens act directly on the nervous system to
      affect the severity of pain. Estrogen receptors (ERs) are expressed by sensory
      neurons, and in trigeminal ganglia, 17beta-estradiol can indirectly enhance
      nociception by stimulating expression and release of prolactin, which increases
      phosphorylation of the nociceptor transducer transient receptor potential
      vanilloid receptor 1 (TRPV1). Here, we show that 17beta-estradiol acts directly
      on dorsal root ganglion (DRG) sensory neurons to reduce TRPV1 activation by
      capsaicin. Capsaicin-induced cobalt uptake and the maximum TRPV1 current induced
      by capsaicin were inhibited when isolated cultured DRGs neurons from adult female
      rats were exposed to 17beta-estradiol (10-100 nm) overnight. There was no effect
      of 17beta-estradiol on capsaicin potency, TRPV1 activation by protons (pH 6-4),
      and P2X currents induced by alpha,beta-methylene-ATP. Diarylpropionitrile (ERbeta
      agonist) also inhibited capsaicin-induced TRPV1 currents, whereas propylpyrazole
      triol (ERalpha agonist) and 17alpha-estradiol (inactive analog) were inactive,
      and 17beta-estradiol conjugated to BSA (membrane-impermeable agonist) caused a
      small increase. TRPV1 inhibition was antagonized by tamoxifen (1 microm), but
      ICI182870 (10 microm) was a potent agonist and mimicked 17beta-estradiol. We
      conclude that TRPV1 in DRG sensory neurons can be inhibited by a nonclassical
      estrogen-signalling pathway that is downstream of intracellular ERbeta. This
      affects the vanilloid binding site targeted by capsaicin but not the TRPV1
      activation site targeted by protons. These actions could curtail the nociceptive
      transducer functions of TRPV1 and limit chemically induced nociceptor
      sensitization during inflammation. They are consistent with clinical reports that
      female pelvic pain can increase after reductions in circulating estrogens.

PMID- 18617619
TI  - Interleukin-1 mediates the anorexic and febrile actions of galanin-like Peptide.
AB  - Galanin-like peptide (GALP) is a neuropeptide that has complex actions on energy
      balance, producing orexigenic effects in the short term in rats but anorexigenic
      and febrile effects over the longer term in rats and mice. GALP is thought to
      promote feeding via neuropeptide Y and orexin neurons, but the mediators of the
      anorexia are unknown. However, the anorexic and febrile actions of GALP are
      similar in magnitude and profile to those seen after central injections of the
      cytokine IL-1. Thus, the aim of this study was to test the hypothesis that IL-1
      mediates the effects of GALP on energy balance. Intracerebroventricular injection
      of GALP (1.5 nmol) in male Sprague-Dawley rats stimulated production of IL-1alpha
      and IL-1beta protein in macrophages and/or microglia in selected brain areas,
      including the meninges, and periventricular brain regions.
      Intracerebroventricular injection of GALP in rats stimulated food intake over 1 h
      but decreased feeding and body weight at 24 h and caused a rise in core body
      temperature over 8 h. Coinfusion of the IL-1 receptor antagonist had no effect on
      the GALP-induced orexigenic response but significantly reduced the longer-term
      actions of GALP observed at 24 h and its effect on body temperature. Furthermore,
      the actions of GALP on feeding, body weight, and body temperature were
      significantly reduced in IL-1alpha/beta-, IL-1beta-, or IL-1 type I receptor (IL
      1RI)-deficient mice. These data suggest that GALP induces expression of IL-1 in
      the brain, and its anorexic and febrile actions are mediated by this cytokine
      acting via IL-1 type I receptor.

PMID- 18617620
TI  - Impaired insulin secretion by diphenyleneiodium associated with perturbation of
      cytosolic Ca2+ dynamics in pancreatic beta-cells.
AB  - Pancreatic islets express the superoxide-producing nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase system, but its role remains unknown. To
      address this, we studied the mechanisms of impaired insulin secretion induced by
      diphenyleneiodium (DPI), an NADPH oxidase inhibitor. We investigated the effects
      of DPI on glucose- and nonfuel-stimulated insulin secretion, islet glucose
      metabolism, and intracellular Ca2+ concentration ([Ca2+]i) dynamics in rat islets
      and beta-cell line RINm5F cells. DPI did not affect insulin secretion at 3.3 mm
      glucose but totally suppressed insulin secretion stimulated by 16.7 mm glucose
      (percentage of control, 9.2 +/- 1.2%; P <0.001). DPI also inhibited insulin
      release by high K+-induced membrane depolarization (percentage of control, 36.0
      +/- 5.3%; P <0.01) and protein kinase C activation (percentage of control, 30.2
      +/- 10.6% in the presence of extracellular Ca2+, P <0.01; percentage of control,
      42.0 +/- 4.7% in the absence of extracellular Ca2+, P <0.01). However, DPI had no
      effect on mastoparan-induced insulin secretion at 3.3 and 16.7 mm glucose under
      Ca2+-free conditions. DPI significantly suppressed islet glucose oxidation and
      ATP content through its known inhibitory action on complex I in the mitochondrial
      respiratory chain. On the other hand, DPI altered [Ca2+]i dynamics in response to
      high glucose and membrane depolarization, and DPI per se dose-dependently
      increased [Ca2+]i. The DPI-induced [Ca2+]i rise was associated with a transient
      increase in insulin secretion and was attenuated by removal of extracellular
      Ca2+, by L-type voltage-dependent Ca2+ channel blockers, by mitochondrial
      inhibitors, or by addition of 0.1 or 1.0 microm H2O2 exogenously. Our results
      showed that DPI impairment of insulin secretion involved altered Ca2+ signaling,
      suggesting that NADPH oxidase may modulate Ca2+ signaling in beta-cells.

PMID- 18617621
TI  - Expression of follistatin-related genes is altered in heart failure.
AB  - Follistatins play roles in diverse biological processes including cell
      proliferation, wound healing, inflammation, and skeletal muscle growth, yet their
      role in the heart is currently unknown. We have investigated the myocardial
      expression profile and cellular distribution of follistatin (FST) and the FST
      like genes FSTL1 and FSTL3 in the normal and failing heart. Expression was
      further analyzed in the novel setting of recovery from heart failure in
      myocardium obtained from patients who received combined mechanical (left
      ventricular assist device) and pharmacological therapy. Real-time PCR revealed
      that FSTL1 and FSTL3 expression was elevated in heart failure but returned to
      normal after recovery. FSTL3 expression levels correlated with molecular markers
      of disease severity and FSTL1 with the endothelial cell marker CD31, suggesting a
      potential link with vascularization. FSTL1 levels before treatment correlated
      with cardiac function after recovery, suggesting initial levels may influence
      long-term outcome. Immunohistochemistry revealed that FST was primarily localized
      to fibroblasts and vascular endothelium within the heart, whereas FSTL1 was
      localized to myocytes, endothelium, and smooth muscle cells and FSLT3 to myocytes
      and endothelium. Microarray analysis revealed that FST and FSTL1 were associated
      with extracellular matrix-related and calcium-binding proteins, whereas FSTL3 was
      associated mainly with cell signaling and transcription. These data show for the
      first time that elevated myocardial expression of FST-like genes is a feature of
      heart failure and may be linked to both disease severity and mechanisms
      underlying recovery, revealing new insight into the pathogenesis of heart failure
      and offering novel therapeutic targets.

PMID- 18617622
TI  - Modulation of osteoclastogenesis by fatty acids.
AB  - Clinical studies have shown that total body fat mass is related to both bone
      density and fracture risk and that fat ingestion reduces bone turnover. These
      effects are at least partially mediated by endocrine mechanisms, but it is
      possible that lipids might act directly on bone. We assessed the effects of broad
      fractions of milk lipids in osteoblasts, bone marrow, and neonatal mouse
      calvariae. Several milk fractions and their hydrolysates inhibited
      osteoclastogenesis in bone marrow cultures, so we assessed the effects of free
      fatty acids in this model. Saturated fatty acids (0.1-10 microg/ml) inhibited
      osteoclastogenesis in bone marrow cultures and RAW264.7 cells. This effect was
      maximal for C14:0 to C18:0 fatty acids. The introduction of greater than 1 double
      bond abrogated this effect; omega3 and omega6 fatty acids had comparable low
      activity. Osteoblast proliferation was modestly increased by the
      antiosteoclastogenic compounds, ruling out a nonspecific toxic effect. Active
      fatty acids did not consistently change expression of receptor activator of
      nuclear factor-kappaB ligand or osteoprotegerin in osteoblastic cells nor did
      they affect the activity of key enzymes in the mevalonate pathway. However,
      receptors known to bind fatty acids were found to be expressed in osteoblastic
      (GPR120) and osteoclastic (GPR40, 41, 43, 120) cells. A synthetic GPR 40/120
      agonist mimicked the inhibitory effects of fatty acids on osteoclastogenesis.
      These findings provide a novel link between lipid and bone metabolism, which
      might contribute to the positive relationship between adiposity and bone density
      as well as provide novel targets for pharmaceutical and nutriceutical
      development.

PMID- 18617623
TI  - Point: maximal oxygen uptake is limited by a central nervous system governor.

PMID- 18617624
TI  - Nicotine administration and withdrawal affect survival in systemic inflammation
      models.
AB  - How different regimens of nicotine administration and withdrawal affect systemic
      inflammation is largely unknown. We studied the effects of chronic and acute
      nicotine administration and of nicotine withdrawal on the outcome of aseptic and
      septic systemic inflammation. Male C57BL/6 mice were implanted with subcutaneous
      osmotic pumps (to deliver nicotine) and intrabrain telemetry probes (to measure
      temperature). Aseptic inflammation was induced by lipopolysaccharide (40 mg/kg
      ip); sepsis was induced by cecal ligation and puncture. The chronic nicotine
      administration group received nicotine (28 mg.kg(-1).day(-1)) for 2 wk before the
      induction of inflammation and continued receiving nicotine until the end of the
      experiment; the acute nicotine administration group received saline for 2 wk and
      nicotine thereafter; the nicotine withdrawal group received nicotine for 2 wk and
      saline thereafter; and the no-nicotine group was infused with saline throughout
      the experiment. Compared with no nicotine, the chronic nicotine administration
      did not affect survival in either model of inflammation, possibly due to the
      development of nicotine tolerance. The acute nicotine administration increased
      the survival rate in aseptic inflammation from 11 to 33% (possibly by suppressing
      inflammation) but worsened the outcome of sepsis (possibly because the
      suppression of inflammation promoted microbial proliferation). Oppositely to
      acute nicotine, nicotine withdrawal increased the survival rate in sepsis from 18
      to 40%. The effects on survival were not due to changes in body temperature. We
      conclude that acute nicotine administration and nicotine withdrawal affect
      survival in systemic inflammation and that these effects strongly depend on
      whether inflammation is aseptic or septic.

PMID- 18617625
TI  - Human cerebral arteriovenous vasoactive exchange during alterations in arterial
      blood gases.
AB  - Cerebral blood flow (CBF) is highly regulated by changes in arterial Pco(2) and
      arterial Po(2). Evidence from animal studies indicates that various vasoactive
      factors, including release of norepinephrine, endothelin, adrenomedullin, C
      natriuretic peptide (CNP), and nitric oxide (NO), may play a role in arterial
      blood gas-induced alterations in CBF. For the first time, we directly quantified
      exchange of these vasoactive factors across the human brain. Using the Fick
      principle and transcranial Doppler ultrasonography, we measured CBF in 12 healthy
      humans at rest and during hypercapnia (4 and 8% CO(2)), hypocapnia (voluntary
      hyperventilation), and hypoxia (12 and 10% O(2)). At each level, blood was
      sampled simultaneously from the internal jugular vein and radial artery. With the
      exception of CNP and NO, the simultaneous quantification of norepinephrine,
      endothelin, or adrenomedullin showed no cerebral uptake or release during changes
      in arterial blood gases. Hypercapnia, but not hypocapnia, increased CBF and
      caused a net cerebral release of nitrite (a marker of NO), which was reflected by
      an increase in the venous-arterial difference for nitrite: 57 +/- 18 and 150 +/-
      36 micromol/l at 4% and 8% CO(2), respectively (both P < 0.05). Release of
      cerebral CNP was also observed during changes in CO(2) (hypercapnia vs.
      hypocapnia, P < 0.05). During hypoxia, there was a net cerebral uptake of
      nitrite, which was reflected by a decreased venous-arterial difference for
      nitrite: -96 +/- 14 micromol/l at 10% O(2) (P < 0.05). These data indicate that
      there is a differential exchange of NO across the brain during hypercapnia and
      hypoxia and that CNP may play a complementary role in CO(2)-induced CBF changes.

PMID- 18617626
TI  - Arterial-ventricular coupling: mechanistic insights into cardiovascular
      performance at rest and during exercise.
AB  - Understanding the performance of the left ventricle (LV) requires not only
      examining the properties of the LV itself, but also investigating the modulating
      effects of the arterial system on left ventricular performance. The interaction
      of the LV with the arterial system, termed arterial-ventricular coupling
      (E(A)/E(LV)), is a central determinant of cardiovascular performance and cardiac
      energetics. E(A)/E(LV) can be indexed by the ratio of effective arterial
      elastance (E(A); a measure of the net arterial load exerted on the left
      ventricle) to left ventricular end-systolic elastance (E(LV); a load-independent
      measure of left ventricular chamber performance). At rest, in healthy
      individuals, E(A)/E(LV) is maintained within a narrow range, which allows the
      cardiovascular system to optimize energetic efficiency at the expense of
      mechanical efficacy. During exercise, an acute mismatch between the arterial and
      ventricular systems occurs, due to a disproportionate increase in E(LV) (from an
      average of 4.3 to 13.2, and 4.7 to 15.5 mmHg.ml(-1).m(-2) in men and women,
      respectively) vs. E(A) (from an average of 2.3 to 3.2, and 2.3 to 2.9 mmHg.ml(
      1).m(-2) in men and women, respectively), to ensure that sufficient cardiac
      performance is achieved to meet the increased energetic requirements of the body.
      As a result E(A)/E(LV) decreases from an average of 0.58 to 0.34, and 0.52 to
      0.27 in men and women, respectively. In this review, we provide an overview of
      the concept of E(A)/E(LV), and examine the effects of age, hypertension, and
      heart failure on E(A)/E(LV) and its components (E(A) and E(LV)) in men and women.
      We discuss these effects both at rest and during exercise and highlight the
      mechanistic insights that can be derived from studying E(A)/E(LV).

PMID- 18617627
TI  - Separate and combined effects of exercise training and weight loss on exercise
      efficiency and substrate oxidation.
AB  - Perturbations in body weight have been shown to affect energy expenditure and
      efficiency during physical activity. The separate effects of weight loss and
      exercise training on exercise efficiency or the proportion of energy derived from
      fat oxidation during physical activity, however, are not known. The purpose of
      this study was to determine the separate and combined effects of exercise
      training and weight loss on metabolic efficiency, economy (EC), and fat oxidation
      during steady-state moderate submaximal exercise. Sixty-four sedentary older (67
      +/- 0.5 yr) overweight to obese (30.7 +/- 0.4 kg/m(2)) volunteers completed 4 mo
      of either diet-induced weight loss (WL; n = 11), exercise training (EX; n = 36),
      or the combination of both interventions (WLEX; n = 17). Energy expenditure,
      gross efficiency (GE), EC, and proportion of energy expended from fat (EF) were
      determined during a 1-h submaximal (50% of peak aerobic capacity) cycle ergometry
      exercise before the intervention and at the same absolute work rate after the
      intervention. We found that EX increased GE by 4.7 +/- 2.2%. EC was similarly
      increased by 4.2 +/- 2.1% by EX. The addition of concomitant WL to EX (WLEX)
      resulted in greater increases in GE (9.0 +/- 3.3%) compared with WL alone but not
      compared with EX alone. These effects remained after adjusting for changes in
      lean body mass. The proportion of energy derived from fat during the bout of
      moderate exercise increased with EX and WLEX but not with WL. From these
      findings, we conclude that exercise training, either alone or in combination with
      weight loss, increases both exercise efficiency and the utilization of fat during
      moderate physical activity in previously sedentary, obese older adults. Weight
      loss alone, however, significantly improves neither efficiency nor utilization of
      fat during exercise.

PMID- 18617628
TI  - The airway response to deep inspirations decreases with COPD severity and is
      associated with airway distensibility assessed by computed tomography.
AB  - In patients with mild chronic obstructive pulmonary disease (COPD), the effect of
      deep inspirations (DIs) to reverse methacholine-induced bronchoconstriction is
      largely attenuated. In this study, we tested the hypothesis that the
      effectiveness of DI is reduced with increasing disease severity and that this is
      associated with a reduction in the ability of DI to distend the airways. Fifteen
      subjects [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I
      II: n = 7; GOLD stage III-IV: n = 8] underwent methacholine bronchoprovocation in
      the absence of DI, followed by DI. The effectiveness of DI was assessed by their
      ability to improve inspiratory vital capacity and forced expiratory volume in 1 s
      (FEV(1)). To evaluate airway distensibility, two sets of high-resolution computed
      tomography scans [at residual volume (RV) and at total lung capacity] were
      obtained before the challenge. In addition, mean parenchymal density was
      calculated on the high-resolution computed tomography scans. We found a strong
      correlation between the response to DI and baseline FEV(1) %predicted (r(2) =
      0.70, P < 0.0001) or baseline FEV(1)/forced vital capacity (r(2) = 0.57, P =
      0.001). RV %predicted and functional residual capacity %predicted correlated
      inversely (r(2) = 0.33, P = 0.02 and r(2) = 0.32, P = 0.03, respectively), and
      parenchymal density at RV correlated directly (r(2) = 0.30, P = 0.03), with the
      response to DI. Finally, the effect of DI correlated to the change in large
      airway area from RV to total lung capacity (r(2) = 0.44, P = 0.01). We conclude
      that loss of the effects of DI is strongly associated with COPD severity and
      speculate that the reduction in the effectiveness of DI is due to the failure to
      expand the lungs because of the hyperinflated state and/or the parenchymal damage
      that prevents distension of the airways with lung inflation.

PMID- 18617629
TI  - Effect of hydration state on resistance exercise-induced endocrine markers of
      anabolism, catabolism, and metabolism.
AB  - Hypohydration (decreased total body water) exacerbates the catabolic hormonal
      response to endurance exercise with unclear effects on anabolic hormones. Limited
      research exists that evaluates the effect of hypohydration on endocrine responses
      to resistance exercise; this work merits attention as the acute postexercise
      hormonal environment potently modulates resistance training adaptations. The
      purpose of this study was to examine the effect of hydration state on the
      endocrine and metabolic responses to resistance exercise. Seven healthy
      resistance-trained men (age = 23 +/- 4 yr, body mass = 87.8 +/- 6.8 kg, body fat
      = 11.5 +/- 5.2%) completed three identical resistance exercise bouts in different
      hydration states: euhydrated (EU), hypohydrated by approximately 2.5% body mass
      (HY25), and hypohydrated by approximately 5.0% body mass (HY50). Investigators
      manipulated hydration status via controlled water deprivation and exercise-heat
      stress. Cortisol, epinephrine, norepinephrine, testosterone, growth hormone,
      insulin-like growth factor-I, insulin, glucose, lactate, glycerol, and free fatty
      acids were measured during euhydrated rest, immediately preceding resistance
      exercise, immediately postexercise, and during 60 min of recovery. Body mass
      decreased 0.2 +/- 0.4, 2.4 +/- 0.4, and 4.8 +/- 0.4% during EU, HY25, and HY50,
      respectively, supported by humoral and urinary changes that clearly indicated
      subjects achieved three distinct hydration states. Hypohydration significantly 1)
      increased circulating concentrations of cortisol and norepinephrine, 2)
      attenuated the testosterone response to exercise, and 3) altered carbohydrate and
      lipid metabolism. These results suggest that hypohydration can modify the
      hormonal and metabolic response to resistance exercise, influencing the
      postexercise circulatory milieu.

PMID- 18617630
TI  - Contrasting effects of isocapnic and hypocapnic hyperventilation on orthostatic
      circulatory control.
AB  - The effects of hyperventilation (HV) on mean arterial pressure (MAP) are
      variable. To identify factors affecting the MAP response to HV, we dissected the
      effects of hypocapnic HV (HHV) and isocapnic HV (IHV) and evaluated the effects
      of acute vs. prolonged HHV. In 11 healthy subjects the cardio- and
      cerebrovascular effects of HHV and IHV vs. normal ventilation were examined for
      15 min in the supine position and also for 15 min during 60 degrees head-up tilt.
      The end-tidal CO(2) of the HHV condition was set at 15-20 mmHg. With HHV in the
      supine position, mean cerebral blood flow velocity (mCBFV) declined [95%
      confidence interval (CI) -43 to -34%], heart rate (HR) increased (95% CI 7 to 16
      beats/min), but MAP did not change (95% CI -1 to 6 mmHg). However, an
      augmentation of the supine MAP was observed in the last 10 min of HHV compared
      with the first 5 min of HHV (95% CI 2 to 12 mmHg). During HHV in the tilted
      position mCBFV declined (95% CI -28 to -12%) and MAP increased (95% CI 3 to 11
      mmHg) without changes in HR. With supine IHV, mCBFV decreased (95% CI -14 to -4%)
      and MAP increased (95% CI 1 to 13 mmHg) without changes in HR. During IHV in the
      tilted position MAP was further augmented (95% CI 11 to 20 mmHg) without changes
      in CBFV or HR. Preventing hypocapnia during HV resulted in a higher MAP,
      suggesting two contrasting effects of HV on MAP: hypocapnia causing
      vasodepression and hyperpnea without hypocapnia acting as a vasopressor.

PMID- 18617631
TI  - Histamine H2 receptor trafficking: role of arrestin, dynamin, and clathrin in
      histamine H2 receptor internalization.
AB  - Agonist-induced internalization of G protein-coupled receptors (GPCRs) has been
      implicated in receptor desensitization, resensitization, and down-regulation. In
      the present study, we sought to establish whether the histamine H2 receptor (H2r)
      agonist amthamine, besides promoting receptor desensitization, induced H2r
      internalization. We further studied the mechanisms involved and its potential
      role in receptor resensitization. In COS7 transfected cells, amthamine induced
      H2r time-dependent internalization, showing 70% of receptor endocytosis after 60
      min exposure to amthamine. Agonist removal led to the rapid recovery of
      resensitized receptors to the cell surface. Similar results were obtained in the
      presence of cycloheximide, an inhibitor of protein synthesis. Treatment with
      okadaic acid, an inhibitor of the protein phosphatase 2A (PP2A) family of
      phosphatases, reduced the recovery of both H2r membrane sites and cAMP response.
      Arrestin 3 but not arrestin 2 overexpression reduced both H2r membrane sites and
      H2r-evoked cAMP response. Receptor cotransfection with dominant-negative mutants
      for arrestin, dynamin, Eps15 (a component of the clathrin-mediated endocytosis
      machinery), or RNA interference against arrestin 3 abolished both H2r
      internalization and resensitization. Similar results were obtained in U937 cells
      endogenously expressing H2r. Our findings suggest that amthamine-induced H2r
      internalization is crucial for H2r resensitization, processes independent of H2r
      de novo synthesis but dependent on PP2A-mediated dephosphorylation. Although we
      do not provide direct evidence for H2r interaction with beta-arrestin, dynamin,
      and/or clathrin, our results support their involvement in H2r endocytosis. The
      rapid receptor recycling to the cell surface and the specific involvement of
      arrestin 3 in receptor internalization further suggest that the H2r belongs to
      class A GPCRs.

PMID- 18617633
TI  - African American physicians and organized medicine, 1846-1968: origins of a
      racial divide.
AB  - Like the nation as a whole, organized medicine in the United States carries a
      legacy of racial bias and segregation that should be understood and acknowledged.
      For more than 100 years, many state and local medical societies openly
      discriminated against black physicians, barring them from membership and from
      professional support and advancement. The American Medical Association was early
      and persistent in countenancing this racial segregation. Several key historical
      episodes demonstrate that many of the decisions and practices that established
      and maintained medical professional segregation were challenged by black and
      white physicians, both within and outside organized medicine. The effects of this
      history have been far reaching for the medical profession and, in particular, the
      legacy of segregation, bias, and exclusion continues to adversely affect African
      American physicians and the patients they serve.

PMID- 18617632
TI  - Syntaxin 1A interaction with the dopamine transporter promotes amphetamine
      induced dopamine efflux.
AB  - The soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein
      syntaxin 1A (SYN1A) interacts with and regulates the function of transmembrane
      proteins, including ion channels and neurotransmitter transporters. Here, we
      define the first 33 amino acids of the N terminus of the dopamine (DA)
      transporter (DAT) as the site of direct interaction with SYN1A. Amphetamine
      (AMPH) increases the association of SYN1A with human DAT (hDAT) in a heterologous
      expression system (hDAT cells) and with native DAT in murine striatal
      synaptosomes. Immunoprecipitation of DAT from the biotinylated fraction shows
      that the AMPH-induced increase in DAT/SYN1A association occurs at the plasma
      membrane. In a superfusion assay of DA efflux, cells overexpressing SYN1A
      exhibited significantly greater AMPH-induced DA release with respect to control
      cells. By combining the patch-clamp technique with amperometry, we measured DA
      release under voltage clamp. At -60 mV, a physiological resting potential, AMPH
      did not induce DA efflux in hDAT cells and DA neurons. In contrast, perfusion of
      exogenous SYN1A (3 microM) into the cell with the whole-cell pipette enabled AMPH
      induced DA efflux at -60 mV in both hDAT cells and DA neurons. It has been shown
      recently that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated
      by AMPH and regulates AMPH-induced DA efflux. Here, we show that AMPH-induced
      association between DAT and SYN1A requires CaMKII activity and that inhibition of
      CaMKII blocks the ability of exogenous SYN1A to promote DA efflux. These data
      suggest that AMPH activation of CaMKII supports DAT/SYN1A association, resulting
      in a mode of DAT capable of DA efflux.

PMID- 18617634
TI  - Achieving racial harmony for the benefit of patients and communities: contrition,
      reconciliation, and collaboration.

PMID- 18617635
TI  - Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo
      costimulatory blockade: results of 2 phase 1 studies.
AB  - We report the outcomes of 24 patients with high-risk hematologic malignancies or
      bone marrow failure (BMF) who received haploidentical bone marrow transplantation
      (BMT) after ex vivo induction of alloantigen-specific anergy in donor T cells by
      allostimulation in the presence of costimulatory blockade. Ninety-five percent of
      evaluable patients engrafted and achieved full donor chimerism. Despite receiving
      a median T-cell dose of 29 x10(6)/kg, only 5 of 21 evaluable patients developed
      grade C (n = 4) or D (n = 1) acute graft-versus-host disease (GVHD), with only
      one attributable death. Twelve patients died from treatment-related mortality
      (TRM). Patients reconstituted T-cell subsets and immunoglobulin levels rapidly
      with evidence of in vivo expansion of pathogen-specific T cells in the early
      posttransplantation period. Five patients reactivated cytomegalovirus (CMV), only
      one of whom required extended antiviral treatment. No deaths were attributable to
      CMV or other viral infections. Only 1 of 12 evaluable patients developed chronic
      GVHD. Eight patients survive disease-free with normal performance scores (median
      follow-up, 7 years). Thus, despite significant early TRM, ex vivo
      alloanergization can support administration of large numbers of haploidentical
      donor T cells, resulting in rapid immune reconstitution with very few viral
      infections. Surviving patients have excellent performance status and a low rate
      of chronic GVHD.

PMID- 18617636
TI  - The Mll partial tandem duplication: differential, tissue-specific activity in the
      presence or absence of the wild-type allele.
AB  - The partial tandem duplication of MLL (MLL-PTD) is found in 5% to 10% of patients
      with acute myeloid leukemia (AML) and normal cytogenetics. Its expression in
      leukemic blasts is coincident with a silenced wild-type (WT) MLL allele. We
      therefore generated mice expressing the Mll-PTD in the absence of Mll-WT. These
      Mll(PTD/-) mice die at birth unlike the normal life expectancy of Mll(PTD/WT),
      Mll(WT/-), and Mll(WT/WT) mice. Using Mll(WT/WT) fetal liver cells (FLC) as
      baseline, we compared Mll(PTD/-) with Mll(PTD/WT) FLC and found both had
      increased HoxA gene expression and granulocyte-macrophage colony-forming
      progenitor cells (CFU-GM); in contrast, only Mll(PTD/WT) FLC had increased
      pluripotent hemopoietic progenitors (CFU-GEMM). The similarities between
      Mll(PTD/WT) and Mll(PTD/-) mice suggest that the Mll-PTD mutation can up-regulate
      target genes in a dominant, gain-of-function fashion. The differences between
      these 2 genotypes suggest that in select tissues the Mll-PTD requires cooperation
      with the Mll-WT in the genesis of the observed abnormality.

PMID- 18617637
TI  - Role of GM-CSF in tolerance induction by mobilized hematopoietic progenitors.
AB  - Mechanisms of protection against autoimmune diseases by transplantation of
      autologous hematopoietic progenitors remain poorly defined. We recently
      demonstrated that, unlike medullary hematopoietic stem cells (HSCs), mobilized
      hematopoietic progenitors (HPCs) stimulate peripheral Foxp3(+) regulatory T cell
      (Treg)-expansion through cell-contact activation of Notch signaling and through
      as yet undetermined soluble factor(s), distinct from TGF-beta1. Herein we
      identified one such soluble factor as granulocyte macrophage-colony stimulating
      factor (GM-CSF), which is produced at higher levels by HPCs than HSCs and whose
      neutralization significantly reduces the growth-promoting effect of HPCs on Treg.
      Treg express a functional GM-CSF receptor alpha-chain CD116 and proliferate in
      response to this cytokine independently from IL2. GM-CSF-expanded Treg-like HPC
      expanded Treg-display enhanced suppressive capacity relative to control Treg.
      Hence, mobilized progenitors stimulate Treg expansion both by cell-contact
      dependent mechanisms and by their production of GM-CSF.

PMID- 18617638
TI  - Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing
      cells.
AB  - The effector T-cell lineage shows great plasticity. Th17 cells are acknowledged
      to be instrumental in the response against microbial infection, but are also
      associated with autoimmune inflammatory processes. Here, we report that human
      regulatory T cells (CD4(pos)CD25(high)Foxp3(pos)CD127(neg)CD27(pos)) can
      differentiate into IL-17-producing cells, when stimulated by allogeneic antigen
      presenting cells, especially monocytes, in the presence of rhIL-2/rhIL-15. These
      regulatory T cell (Treg)-derived IL-17-producing cells showed high expression of
      the Th17-related transcription factor RORgammat and were positively identified by
      CCR6 expression. This differentiation process was enhanced by exogenous IL-1beta,
      IL-23, and IL-21, whereas IL-6 or TGFbeta did not affect the emergence of IL-17
      producing cells. The addition of IL-1 receptor antagonist (IL-1Ra), but not anti
      IL-23 antibody, reduced IL-17-producing cell numbers. When an histone deacetylase
      (HDAC) inhibitor trichostatin A (TSA) was evaluated, we found a profound negative
      effect on the emergence of IL-17-producing cells from Tregs, implying that Treg
      differentiation into IL-17-producing cells depends on histone/protein deacetylase
      activity. Thus, the data suggest that epigenetic modification underlies the
      phenomenon of Treg plasticity here described.

PMID- 18617639
TI  - ARG1 is a novel bronchodilator response gene: screening and replication in four
      asthma cohorts.
AB  - RATIONALE: Inhaled beta-agonists are one of the most widely used classes of drugs
      for the treatment of asthma. However, a substantial proportion of patients with
      asthma do not have a favorable response to these drugs, and identifying genetic
      determinants of drug response may aid in tailoring treatment for individual
      patients. OBJECTIVES: To screen variants in candidate genes in the steroid and
      beta-adrenergic pathways for association with response to inhaled beta-agonists.
      METHODS: We genotyped 844 single nucleotide polymorphisms (SNPs) in 111 candidate
      genes in 209 children and their parents participating in the Childhood Asthma
      Management Program. We screened the association of these SNPs with acute response
      to inhaled beta-agonists (bronchodilator response [BDR]) using a novel algorithm
      implemented in a family-based association test that ranked SNPs in order of
      statistical power. Genes that had SNPs with median power in the highest quartile
      were then taken for replication analyses in three other asthma cohorts.
      MEASUREMENTS AND MAIN RESULTS: We identified 17 genes from the screening
      algorithm and genotyped 99 SNPs from these genes in a second population of
      patients with asthma. We then genotyped 63 SNPs from four genes with significant
      associations with BDR, for replication in a third and fourth population of
      patients with asthma. Evidence for association from the four asthma cohorts was
      combined, and SNPs from ARG1 were significantly associated with BDR. SNP
      rs2781659 survived Bonferroni correction for multiple testing (combined P value =
      0.00048, adjusted P value = 0.047). CONCLUSIONS: These findings identify ARG1 as
      a novel gene for acute BDR in both children and adults with asthma.

PMID- 18617640
TI  - Pneumonia in HIV-infected persons: increased risk with cigarette smoking and
      treatment interruption.
AB  - RATIONALE: Bacterial pneumonia is a major cause of morbidity for HIV-infected
      persons and contributes to excess mortality in this population. OBJECTIVES: To
      evaluate the frequency and risk factors for occurrence of bacterial pneumonia in
      the present era of potent antiretroviral therapy. METHODS: We evaluated data from
      a randomized trial of episodic antiretroviral therapy. The study, Strategies for
      Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in
      33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis
      of bacterial pneumonia was confirmed by a blinded clinical-events committee.
      MEASUREMENTS AND MAIN RESULTS: During a mean follow-up of 16 months, 116
      participants (2.2%) developed at least one episode of bacterial pneumonia.
      Patients randomized to receive episodic antiretroviral therapy were significantly
      more likely to develop pneumonia than patients randomized to receive continuous
      antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P
      = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than
      an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82;
      95% confidence interval, 1.09-3.04; P = 0.02). Participants who were on
      continuous HIV treatment and were current smokers were three times more likely to
      develop bacterial pneumonia than nonsmokers. Current smoking status was
      significant, but a past history of smoking was not. CONCLUSIONS: Bacterial
      pneumonia is a major source of morbidity, even for persons on potent
      antiretroviral therapy, including those with high CD4 cells. Efforts to reduce
      this illness should stress the importance of uninterrupted antiretroviral therapy
      and attainment and/or maintenance of nonsmoking status.

PMID- 18617641
TI  - Portopulmonary hypertension: survival and prognostic factors.
AB  - RATIONALE: Portopulmonary hypertension (PoPH) can be defined as elevation of
      pulmonary arterial pressure and pulmonary vascular resistance in the setting of
      portal hypertension. Survival results in PoPH are contrasting, and prognostic
      factors need to be identified. OBJECTIVES: To analyze long-term survival in a
      large cohort of patients with PoPH with the aim of determining the independent
      variables affecting survival. METHODS: We retrospectively analyzed charts of all
      patients referred to the French Referral Center for pulmonary arterial
      hypertension with the diagnosis of PoPH between 1984 and 2004. MEASUREMENTS AND
      MAIN RESULTS: The study population comprised 154 patients; 57% male. Mean age at
      diagnosis was 49 +/- 11 years, 60% of patients were in New York Heart Association
      functional class III-IV, and mean 6-minute walk distance was 326 +/- 116 m.
      Hemodynamic measurements showed a mean pulmonary arterial pressure of 53 +/- 13
      mm Hg, cardiac index of 2.9 +/- 0.9 L/min/m(2), and pulmonary vascular resistance
      of 752 +/- 377 dyn/s/cm(5). Portal hypertension was related to cirrhosis in 136
      patients, with a severity assessed as follows: Child-Pugh class A 51%, Child-Pugh
      class B 38%, Child-Pugh class C 11%. Overall survival rates at 1, 3, and 5 yr
      were 88, 75, and 68%, respectively. Multivariate regression analysis
      individualized the presence and severity of cirrhosis and cardiac index as major
      independent prognostic factors. CONCLUSIONS: Prognosis in PoPH is mainly related
      to the presence and severity of cirrhosis and to cardiac function. The place of
      pulmonary arterial hypertension-specific therapies remains to be determined in
      the setting of PoPH.

PMID- 18617642
TI  - CD28 down-regulation on CD4 T cells is a marker for graft dysfunction in lung
      transplant recipients.
AB  - RATIONALE: Repeated antigen-driven proliferations cause CD28 on T cells to down
      regulate. We hypothesized that alloantigen-induced proliferations could cause
      CD28 down-regulation in lung transplant recipients. OBJECTIVES: To ascertain if
      CD28 down-regulation on CD4 T cells associated with manifestations of allograft
      dysfunction in lung transplant recipients. METHODS: Peripheral blood CD4 T cells
      from 65 recipients were analyzed by flow cytometry, cytokine multiplex and
      proliferative assays, and correlated with clinical events. MEASUREMENTS AND MAIN
      RESULTS: Findings that CD28 was present on less than 90% of total CD4 T cells
      were predominantly seen among the recipients with bronchiolitis obliterans
      syndrome (specificity = 88%). Perforin and granzyme B were produced by >50% of
      the CD4(+)CD28(null) cells, but less than 6% of autologous CD4(+)CD28(+) cells (P
      < 0.006). CD4(+)CD28(null) cells also had increased productions of
      proinflammatory cytokines, but less frequently expressed regulatory T-cell marker
      FoxP3 (2.1 +/- 1.3%), compared with autologous CD4(+)CD28(+) (9.5 +/- 1.4; P =
      0.01). Cyclosporine A (100 ng/ml) inhibited proliferation of CD4(+)CD28(null)
      cells by 33 +/- 11% versus 68 +/- 12% inhibition of CD4(+)CD28(+) (P = 0.025).
      FEV(1) fell 6 months later (0.35 +/- 0.04 L) in recipients with
      CD4(+)CD28(+)/CD4(total) less than 90% (CD28% Low) compared with 0.08 +/- 0.08 L
      among CD4(+)CD28(+)/CD4(total) (CD28% High) greater than 90% (CD28% High)
      recipients (P = 0.013). Two-year freedom from death or retransplantation in CD28%
      Low recipients was 32 +/- 10% versus 78 +/- 6% among the CD28% High subjects (P <
      0.0001). CONCLUSIONS: CD28 down-regulation on CD4 cells is associated with
      bronchiolitis obliterans syndrome and poor outcomes in lung transplantation
      recipients. CD4(+)CD28(null) cells have unusual, potentially pathogenic
      characteristics, and could be important in the progression of allograft
      dysfunction. These findings may illuminate a novel paradigm of transplantation
      immunopathogenesis, and suggest that CD28 measurements could identify recipients
      at risk for clinical deteriorations.

PMID- 18617643
TI  - VEGF stimulates HDAC7 phosphorylation and cytoplasmic accumulation modulating
      matrix metalloproteinase expression and angiogenesis.
AB  - OBJECTIVE: Histone acetylation/deacetylation plays an important role in the
      control of gene expression, tissue growth, and development. In particular,
      histone deacetylases 7 (HDAC7), a member of class IIa HDACs, is crucial in
      maintaining vascular integrity. However, whether HDAC7 is involved in the
      processes of vascular endothelial signaling and angiogenesis remains unclear.
      Here, we investigated the role of HDAC7 in vascular endothelial growth factor
      (VEGF) signaling and angiogenesis. METHODS AND RESULTS: We show for the first
      time that VEGF stimulated phosphorylation of HDAC7 at the sites of Ser178,
      Ser344, and Ser479 in a dose- and time-dependent manner, which leads to the
      cytoplasmic accumulation of HDAC7. Using pharmacological inhibitors, siRNA, and
      adenoviruses carrying dominant-negative mutants, we found that phospholipase
      Cgamma/protein kinase C/protein kinase D1 (PKD1)-dependent signal pathway
      mediated HDAC7 phosphorylation and cytoplasmic accumulation by VEGF. Infection of
      ECs with adenoviruses encoding a mutant of HDAC7 specifically deficient in PKD1
      dependent phosphorylation inhibited VEGF-induced angiogenic gene expression,
      including matrix metalloproteinases MT1-matrix metalloproteinase (MMP) and MMP10.
      Moreover, HDAC7 and its targeting genes were involved in VEGF-stimulated
      endothelial cell migration, tube formation, and microvessel sprouting.
      CONCLUSIONS: Our results demonstrate that VEGF stimulates PKD1-dependent HDAC7
      phosphorylation and cytoplasmic accumulation in endothelial cells modulating gene
      expression and angiogenesis.

PMID- 18617644
TI  - Macrophages and platelets are the major source of protease nexin-1 in human
      atherosclerotic plaque.
AB  - OBJECTIVE: Protease nexin-1 (PN-1), a serpin constitutively expressed by vascular
      smooth muscle cells and endothelial cells, inhibits thrombin, plasminogen
      activators, and plasmin and can thus be expected to play a role in vascular
      biology. The present study addressed the question of PN-1 expression in human
      atherothrombosis. METHODS AND RESULTS: Immunohistochemistry and biochemical
      studies confirmed that PN-1 was expressed at a moderate level in the medial layer
      of normal human arteries and showed that PN-1 expression was increased in
      atherothrombotic lesions. In early noncomplicated plaques, PN-1 was associated
      with infiltrating mononuclear cells. A strong PN-1 signal was observed in
      advanced lesions, principally in intraplaque hemorrhage-related structures.
      Monocytes/macrophages and platelets were identified as the main sources of PN-1
      within atherothrombotic material. Isolated human monocytes and platelets both
      expressed high levels of active PN-1, and monocyte PN-1 expression was
      upregulated, at both messenger and protein levels, in response to stimulation by
      lipopolysaccharides. In contrast, PN-1 expression was downregulated during their
      differentiation into macrophages which were shown to produce degraded forms of PN
      1. CONCLUSIONS: Platelets and monocytes/macrophages are a major source of PN-1 in
      human atherothrombotic plaques. PN-1 could thus represent a new actor in the
      evolution of atherosclerotic lesions.

PMID- 18617645
TI  - Longitudinal change in serum gamma-glutamyltransferase and cardiovascular disease
      mortality: a prospective population-based study in 76,113 Austrian adults.
AB  - OBJECTIVE: The purpose of this study was to investigate the association of
      longitudinal change in serum gamma-glutamyltransferase (GGT) with mortality from
      cardiovascular disease (CVD). METHODS AND RESULTS: A population-based cohort of
      76,113 Austrian men and women with 455,331 serial GGT measurements was
      prospectively followed-up for a median of 10.2 years after assessment of
      longitudinal GGT change during an average period of 6.9 years. Cox proportional
      hazards regression with time-varying covariates was used to evaluate GGT change
      as an independent predictor for CVD death. Independently of baseline GGT and
      other classical CVD risk factors, a pronounced increase in GGT (7-year change
      >9.2 U/L) was significantly associated with increased total CVD mortality in men
      (P=0.005); the adjusted hazard ratio (95% confidence interval) in comparison to
      stable GGT (7-year change -0.7 to 1.3 U/L) was 1.40 (1.09 to 1.81). Similarly,
      total CVD risk was elevated for increasing GGT in women, although effects were
      less pronounced and statistically significant only in subanalyses regarding
      coronary heart disease. Age of participants significantly modified the relation
      between GGT change and CVD mortality, with markedly stronger associations to be
      observable for younger individuals. CONCLUSIONS: Our study is the first to
      demonstrate that a longitudinal increase in GGT, independently of baseline GGT
      and even within its normal range, significantly increases risk of fatal CVD.

PMID- 18617646
TI  - Brief report: accelerated atherosclerosis in low-density lipoprotein receptor
      deficient mice lacking the membrane-bound complement regulator CD59.
AB  - OBJECTIVE: Whereas studies in humans and animal models have suggested a role for
      complement activation in atherosclerosis, there has been little analysis of the
      importance of complement regulators. We tested the hypothesis that the terminal
      pathway inhibitor CD59 plays an essential role in limiting the proinflammatory
      effects of complement activation. METHODS AND RESULTS: CD59 gene targeted mice
      (CD59a(-/-)) mice were crossed with low-density lipoprotein receptor-deficient
      (Ldlr(-/-)) mice. CD59-deficient Ldlr(-/-) mice had significantly more extensive
      en face Sudan IV staining of thoracoabdominal aorta than Ldlr(-/-) single knock
      outs, both after a low-fat diet (6.51+/-0.36% versus 2.63+/-0.56%, P<0.001) or a
      high-fat diet (17.05+/-2.15% versus 7.69+/-1.17%, P<0.004). Accelerated lesion
      formation in CD59a(-/-)/Ldlr(-/-) mice on a high-fat diet was associated with
      increased lesional vascular smooth muscle cell (VSMC) number and fibrous cap
      formation. CONCLUSIONS: Our data show that CD59 deficiency accelerates the
      development of lesions and increases plaque VSMC composition. Assuming that the
      main function of CD59 is to prevent the development of C5b-9 membrane attack
      complexes, our observations are consistent with the terminal complement pathway
      having proatherogenic potential in the Ldlr(-/-) mouse model, and highlight the
      importance of complement regulation.

PMID- 18617647
TI  - Absence of hyperlipidemia in LDL receptor-deficient mice having apolipoprotein
      B100 without the putative receptor-binding sequences.
AB  - OBJECTIVE: To examine the effects of apoB100 structure, specifically a mutation
      in the LDLr binding region, on the production of LDL and development of
      atherosclerosis in vivo. METHODS AND RESULTS: Ldlr(-/-)Apobec1(-/-) mice lacking
      the LDLR and apoB editing enzyme accumulated LDL in plasma and developed severe
      atherosclerosis when they had wild-type apoB100. In marked contrast, in Ldlr(-/
      )Apobec1(-/-) mice carrying the Apob100-beta mutation, in the 2 putative LDLR
      binding domains of apoB prevented both LDL accumulation and atherosclerosis.
      Intestinal absorption of lipids and triglyceride secretion from the liver were
      not affected. However, the VLDL particles with apoB100-beta were larger in volume
      by about 70%, and carried approximately four times as much apoE per particle.
      ApoB100-beta synthesis rate in the primary hepatocytes was normal, but its
      intracellular degradation was enhanced. Additionally, mutant apoB100 VLDL cleared
      from the circulation more quickly in vivo through apoE-LRP-mediated mechanism
      than VLDL with wild-type apoB100. In contrast, uptake of the 2 VLDL by
      macrophages were not different. CONCLUSIONS: While conformational change to
      apoB100 during conversion of VLDL to LDL exposes LDLR binding domains and
      facilitates LDLR-mediated lipoprotein clearance, it may also inhibit LRP-mediated
      VLDL uptake and contribute to LDL accumulation in familial hypercholesterolemia.

PMID- 18617648
TI  - Mechanisms of the factor V Leiden paradox.
AB  - OBJECTIVE: Carriers of the factor V Leiden mutation (FVL-carriers) have a
      substantially increased risk of deep venous thrombosis (DVT), whereas the risk of
      pulmonary embolism (PE) is only mildly increased compared with noncarriers. So
      far few studies have investigated possible mechanisms for this so-called FVL
      paradox. METHODS AND RESULTS: Consecutive patients with a first DVT or PE were
      included in a large population-based case-control study (MEGA study). Patients,
      aged 18 to 70 years, provided a questionnaire, DNA (n=3313), or plasma (n=1474).
      Surgery, injury, and travel were considered thrombosis-provocative. Of 2063
      patients with isolated DVT, 20% were FVL-carrier, as were 8% of the 885 patients
      with isolated PE. Among DVT patients, FVL-carriers had their thrombi more often
      proximal and a higher number of affected veins than noncarriers. No differences
      were observed between FVL-carriers and noncarriers in time between provocation
      and diagnosis, in vitro coagulation time, and thrombus density. Compared with
      patients with both DVT and PE, isolated DVT patients more often had thrombi
      located distally and had a similar number of affected veins. Compared with
      isolated PE patients, isolated DVT patients had a similar time between
      provocation and diagnosis, and similar in vitro coagulation time and thrombus
      density. CONCLUSIONS: Although some effects were differential for FVL-carriers
      and noncarriers, and some were differential for PE and DVT patients, none of the
      potential mechanisms offered a clear explanation.

PMID- 18617649
TI  - ApoA-I facilitates ABCA1 recycle/accumulation to cell surface by inhibiting its
      intracellular degradation and increases HDL generation.
AB  - OBJECTIVE: Calpain-mediated proteolysis is one of the major regulatory factors
      for activity of ATP-binding cassette transporter (ABC) A1. Helical
      apolipoproteins protect ABCA1 against this degradation and increase generation of
      HDL. We investigated the mechanism for this reaction focusing on roles of
      endocytotic internalization of ABCA1. METHODS AND RESULTS: Surface ABCA1 was
      labeled with biotin and traced for its internalization and degradation. ABCA1 in
      the cell surface was internalized within 10 minutes regardless of the presence of
      apoA-I. ABCA1 was intracellularly degraded and was protected against this only
      when exposed to extracellular apoA-I before its endocytosis. Consequently,
      recycle of ABCA1 to the surface was enhanced, and surface ABCA1 was increased by
      apoA-I. Direct inhibition of ABCA1 endocytosis led to decrease of its degradation
      and increase of surface ABCA1. Generation of HDL increased in parallel with
      surface ABCA1. CONCLUSIONS: Surface ABCA1 is internalized and degraded, and apoA
      I interferes with only the latter step to recycle ABCA1 to the surface. Increase
      of surface ABCA1 results in the increase of generation of HDL.

PMID- 18617650
TI  - High-density lipoprotein reduces the human monocyte inflammatory response.
AB  - OBJECTIVE: Whereas the anti-inflammatory effects of high-density lipoprotein
      (HDL) on endothelial cells are well described, such effects on monocytes are less
      studied. METHODS AND RESULTS: Human monocytes were isolated from whole blood
      followed by assessment of CD11b activation/expression and cell adhesion under
      shear-flow. HDL caused a dose-dependent reduction in the activation of CD11b
      induced by PMA or receptor-dependent agonists. The constituent of HDL responsible
      for the antiinflammatory effects on CD11b activation was found to be
      apolipoprotein A-I (apoA-I). Cyclodextrin, but not cyclodextrin/cholesterol
      complex, also inhibited PMA-induced CD11b activation implicating cholesterol
      efflux as the main mechanism. This was further confirmed with the demonstration
      that cholesterol content of lipid rafts diminished after treatment with the
      cholesterol acceptors. Blocking ABCA1 with an anti-ABCA1 antibody abolished the
      effect of apoA-I. Furthermore, monocytes derived from a Tangier disease patient
      definitively confirmed the requirement of ABCA1 in apoA-I-mediated CD11b
      inhibition. The antiinflammatory effects of apoA-I were also observed in
      functional models including cell adhesion to an endothelial cell monolayer,
      monocytic spreading under shear flow, and transmigration. CONCLUSIONS: HDL and
      apoA-I exhibit an antiinflammatory effect on human monocytes by inhibiting
      activation of CD11b. ApoA-I acts through ABCA1, whereas HDL may act through
      several receptors.

PMID- 18617651
TI  - Alcohol consumption and mortality from stroke and coronary heart disease among
      Japanese men and women: the Japan collaborative cohort study.
AB  - BACKGROUND AND PURPOSE: Previous studies have demonstrated the association
      between alcohol consumption and cardiovascular mortality. However, the sex
      specific association between alcohol consumption and mortality from stroke and
      coronary heart disease remains unclear. METHODS: Between 1988 and 1990, 34,776
      men and 48 906 women aged 40 to 79 years completed a self-administered
      questionnaire including information about alcohol consumption. They were followed
      up for a median duration of 14.2 years. RESULTS: Of the 83,682 respondents, 1628
      died from stroke and 736 died from coronary heart disease. For men, heavy
      drinking (>or=46.0 g ethanol/day) was associated with increased mortality from
      total, hemorrhagic, and ischemic strokes, whereas light-to-moderate drinking was
      associated with reduced mortality from total cardiovascular disease, compared
      with not drinking. The respective multivariable hazard ratios (95% CI) were 1.48
      (1.22 to 1.80) for total stoke, 1.67 (1.17 to 2.38) for hemorrhagic stroke, 1.35
      (1.04 to 1.75) for ischemic stroke, and 0.88 (0.78 to 1.00) for total
      cardiovascular disease. Women who were heavy drinkers (>or=46.0 g ethanol/day)
      showed increased mortality from coronary heart disease, and there was reduced
      mortality from total cardiovascular disease for drinkers of 0.1 to 22.9 g ethanol
      per day compared with mortality for nondrinkers. The respective multivariable
      hazard ratios (95% CI) for the 2 categories of drinkers were 4.10 (1.63 to 10.3)
      and 0.75 (0.62 to 0.91). CONCLUSIONS: Heavy alcohol consumption is associated
      with increased mortality from total stroke, particularly hemorrhagic stroke, and
      total cardiovascular disease for men, and from coronary heart disease for women,
      whereas light-to-moderate drinking may be associated with reduced mortality from
      cardiovascular disease for both sexes.

PMID- 18617652
TI  - Prevalence and correlates of subclinical atherosclerosis in Alaska Eskimos: the
      GOCADAN study.
AB  - BACKGROUND AND PURPOSE: The recent increase in clinical cardiovascular disease in
      Alaska Eskimos suggests that changes in traditional lifestyle may have adverse
      public health consequences. This study examines the prevalence of subclinical
      vascular disease and its relation to risk factors in Alaska Eskimos. METHODS:
      Participants in the population-based Genetics of Coronary Artery Disease in
      Alaska Natives (GOCADAN) Study underwent evaluation of cardiovascular disease
      risk factors and carotid ultrasound. Outcome variables were carotid intimal
      medial thickness and presence and extent of atherosclerosis. RESULTS: In
      multivariate analyses, intimal-medial thickness and presence and extent of
      atherosclerosis were all associated with traditional cardiovascular disease risk
      factors but not dietary intake of omega-3 fatty acids. Rates of carotid
      atherosclerosis were higher than those reported in 2 large population-based US
      studies. CONCLUSIONS: Alaska Eskimos have similar traditional risk factors for
      carotid atherosclerosis as other ethnic and racial populations but have higher
      prevalences of atherosclerosis, possibly attributable to higher rates of smoking.

PMID- 18617653
TI  - Longitudinal analysis of quality of life for stroke survivors using latent curve
      models.
AB  - BACKGROUND AND PURPOSE: For the survivors, activities of daily living, handicap,
      and depression have a significant impact on health-related quality of life
      (HRQOL). How the dynamic changes of these variables relate to HRQOL over time in
      the subacute phase of stroke recovery has not been investigated. The objective of
      this study was to study longitudinal behaviors of HRQOL of the stroke survivors
      in relation to the changes in activities of daily living, handicap, and
      depression after stroke. METHODS: This was a prospective cohort study of first
      disabling patients with stroke. Subjects were interviewed at 3, 6, and 12 months
      after stroke for modified Barthel Index, London Handicap Scale, Geriatric
      Depression Scale, and the World Health Organization Quality of Life questionnaire
      (abbreviated Hong Kong version). A latent curve model was developed to analyze
      how the dynamic changes in activities of daily living, handicap, and depressive
      mood related to the changes in HRQOL. RESULTS: Two hundred forty-seven of 303
      patients (82%) followed up at 3 months after stroke could complete the quality-of
      life questionnaire. Their mean age was 68.8 years. The latent curve model
      analysis revealed that initial physical health HRQOL was independently associated
      with activities of daily living, handicap, and depression. The other 3 HRQOL
      domain scores were primarily associated with depression only. The rates of change
      in all 4 domains of HRQOL were significantly and inversely associated with rate
      of change in the Geriatric Depression Scale only. CONCLUSIONS: Change in mood in
      the postacute phase of stroke recovery is the most significant determinant of
      change in HRQOL. More attention should be paid to the detection and management of
      poststroke depression.

PMID- 18617655
TI  - The association between kidney disease and cardiovascular risk in a multiethnic
      cohort: findings from the Northern Manhattan Study (NOMAS).
AB  - BACKGROUND AND PURPOSE: The objective of this study was to determine the
      relationship between chronic kidney disease (CKD), race-ethnicity, and vascular
      outcomes. METHODS: A prospective, multiracial cohort of 3298 stroke-free subjects
      with 6.5 years of mean follow-up time for vascular outcomes (stroke, myocardial
      infarction, vascular death) was used. Kidney function was estimated using serum
      creatinine and Cockcroft-Gault formula. Cox proportional hazards models were
      fitted to evaluate the relationship between kidney function and vascular
      outcomes. RESULTS: In multivariate analysis, Cockcroft-Gault formula between 15
      and 59 mL/min was associated with a significant 43% increased stroke risk in the
      overall cohort. Blacks with Cockcroft-Gault formula between 15 and 59 mL/min had
      significantly increased risk of both stroke (hazard ratio, 2.65; 95% CI, 1.47 to
      4.77) and combined vascular outcomes (hazard ratio, 1.59; 95% CI, 1.10-2.92).
      CONCLUSIONS: Chronic kidney disease is a significant risk factor for stroke and
      combined vascular events, especially in blacks.

PMID- 18617656
TI  - High prevalence of supine sleep in ischemic stroke patients.
AB  - BACKGROUND AND PURPOSE: Sleep apnea is very common after stroke and is associated
      with poor outcome. Supine sleep is known to exacerbate apneas in the general
      sleep apnea population. We therefore investigated the pattern of sleep positions
      in the acute stroke period. METHODS: Inpatients with acute ischemic stroke
      underwent full polysomnography that included continuous monitoring of sleep
      positions. Sleep apnea severity was measured using the apnea-hypopnea index
      (AHI). Stroke severity was measured by the NIH Stroke Scale (NIHSS) at the time
      of study enrollment by certified study personnel. Percent total sleep time spent
      in the supine position was calculated and compared by stroke severity based on a
      median split of NIHSS using a Wilcoxon rank-sum test. RESULTS: Of the 30
      patients, the median age was 67. The median AHI was 23 (IQR: 6, 47). Twenty-two
      patients (73%) had sleep apnea with an AHI >/=5. The vast majority of sleep time
      among the stroke cases was spent supine, with a median percent sleep time spent
      supine of 100 (IQR: 62, 100). The majority (63%) of subjects spent no time asleep
      in any of the nonsupine positions (prone, left, right). Median percent sleep time
      supine was 100 (IQR: 100, 100) in those with a higher NIHSS and 63 (IQR: 51, 100)
      in those with a lower NIHSS (P<0.01). CONCLUSIONS: Given the high prevalence of
      supine sleep identified, research into positional therapy for stroke patients
      with sleep apnea seems warranted.

PMID- 18617657
TI  - Deletion of angiotensin II type 2 receptor attenuates protective effects of bone
      marrow stromal cell treatment on ischemia-reperfusion brain injury in mice.
AB  - BACKGROUND AND PURPOSE: Protective effects of bone marrow stromal cells (MSCs) on
      ischemic brain damage have been highlighted. We examined the possibility that
      deletion of AT(2) receptor could attenuate the cerebroprotective effects of MSC
      using AT(2) receptor-deficient mice (Agtr2 (-)) and the effect of selective AT(1)
      receptor blocker. METHODS: Wild-type mice (Agtr2 (+)) were subjected to 3 hours
      of focal brain ischemia followed by reperfusion (ischemia-reperfusion injury).
      Simultaneously, Agtr2 (+)-MSC, Agtr2 (-)-MSC, or saline was injected through the
      tail vein. RESULTS: Survival rates at 6 days after ischemia-reperfusion injury
      were as follows: approximately 50% in saline-injected mice, 80% in Agtr2 (+)-MSC
      injected mice, and 20% in Agtr2 (-)-MSC-injected mice. Neurological deficit after
      ischemia-reperfusion injury was improved in Agtr2 (+)-MSC-injected mice, but not
      in Agtr2 (-)-MSC-injected mice. After 48 hours of ischemia-reperfusion injury,
      brain infarct size was reduced in Agtr2 (+)-MSC-injected mice, but not in Agtr2 (
      )-MSC-injected mice. Moreover, brain edema was significantly ameliorated in Agtr2
      (+)-MSC-treated mice but not in Agtr2 (-)-MSC-treated mice. Furthermore, the
      increase in mRNA expression of tumor necrosis factor-alpha and monocyte
      chemoattractant protein-1 in the ischemic brain was less in Agtr2 (+)-MSC-treated
      mice in the ipsilateral site, but was similar in the contralateral hemisphere.
      Tumor necrosis factor-alpha level was increased in both the contralateral
      hemisphere and ipsilateral hemisphere of Agtr2 (-)-MSC-treated mice. In contrast,
      monocyte chemoattractant protein-1 levels tended to increase Agtr2 (-)-MSC
      treated mice without a significant difference. Treatment of MSC with an AT(1)
      receptor blocker, valsartan, significantly improved survival rates in Agtr2 (-)
      MSC-injected mice. CONCLUSIONS: These results suggest that AT(2) receptor
      signaling in MSC attenuated brain damage and neurological deficit (deleted).

PMID- 18617658
TI  - Recurrent events in transient ischemic attack and minor stroke: what events are
      happening and to which patients?
AB  - BACKGROUND AND PURPOSE: The risk of a recurrent stroke after transient ischemic
      attack (TIA) or minor stroke is high. Clinical trials are needed to assess acute
      treatment options in these patients. We sought to evaluate the type of recurrent
      events and to identify which subsets of patients are at risk for recurrent
      events. METHODS: One hundred and eighty patients with TIA or minor stroke were
      examined within 12 hours and underwent brain MRI within 24 hours. Any
      neurological deterioration was recorded, and a combination of clinical and MRI
      factors were used to create a combined event classification. Subgroups of
      patients analyzed included classical TIA, patients with NIHSS=0, and patients
      with NIHSS >0 in ED. RESULTS: Overall there were 38 events in 36 patients (20%
      event rate); 20 were symptomatic and 18 were silent (only evident because of the
      follow up MRI). 18/20 (90%) symptomatic events were associated with progression
      of presenting symptoms, compared to 2/20 (10%) with a clear recurrent stroke
      distinct from the original event. We found a low risk of recurrent stroke among
      classical definition TIA patients (1.1%). Patients with an NIHSS=0 in the ED, had
      an intermediate event rate (6.6%) between TIA (classical - 1.1%) and NIHSS >0
      (14.4%; chi(2) test for trend, P=0.02). All clinical categories of patient (TIA,
      stroke, NIHSS=0) accumulated silent lesions on MRI. CONCLUSIONS: Most events were
      classified as stroke progression or infarct growth rather than a recurrent
      stroke. A low risk of recurrence was found in patients with classical TIA and
      those with no neurological deficits on initial assessment.

PMID- 18617654
TI  - Relative effects of statin therapy on stroke and cardiovascular events in men and
      women: secondary analysis of the Stroke Prevention by Aggressive Reduction in
      Cholesterol Levels (SPARCL) Study.
AB  - BACKGROUND AND PURPOSE: In SPARCL, treatment with atorvastatin 80 mg daily
      reduced stroke risk in patients with recent stroke or TIA and no known coronary
      heart disease by 16% versus placebo over 4.9 years of follow-up. The purpose of
      this secondary analysis was to determine whether men and women similarly
      benefited from randomization to statin treatment. METHODS: The effect of sex on
      treatment-related reductions in stroke and other cardiovascular outcomes were
      analyzed with Cox regression modeling testing for sex by treatment interactions.
      RESULTS: Women (n=1908) constituted 40% of the SPARCL study population. At
      baseline, men (n=2823) were younger (62.0+/-0.21 versus 63.9+/-0.27 years), had
      lower systolic BPs (138.1+/-0.35 versus 139.5+/-0.47 mm Hg), higher diastolic BPs
      (82.2+/-0.20 versus 81.0+/-0.25 mm Hg), more frequently had a history of smoking
      (73% versus 38%), and had lower total cholesterol (207.0+/-0.54 versus 218.9+/
      0.67 mg/dL) and LDL-C levels (132+/-0.45 versus 134+/-0.57 mg/dL) than women. Use
      of antithrombotics and antihypertensives were similar. After prespecified
      adjustment for region, entry event, time since event, and age, there were no sex
      by treatment interactions for the combined risk of nonfatal and fatal stroke
      (treatment Hazard Ratio, HR=0.84, 95% CI 0.68, 1.02 in men versus HR=0.84, 95% CI
      0.63, 1.11 in women; treatment x sex interaction P=0.99), major cardiac events
      (HR=0.61, 95% CI 0.42, 0.87 in men versus HR=0.76, 95% CI 0.48, 1.21 in women;
      P=0.45), major cardiovascular events (HR=0.78, 95% CI 0.65, 0.93 in men versus
      HR=0.84, 95% CI 0.65, 1.07 in women; P=0.63), revascularization procedures
      (HR=0.50, 95% CI 0.37, 0.67 in men versus HR=0.76, 95% CI 0.46, 1.24 in women;
      P=0.17), or any CHD event (HR=0.54, 95% CI 0.41, 0.72 in men versus 0.67 95% CI
      0.46, 0.98 in women; P=0.40). CONCLUSIONS: Stroke and other cardiovascular events
      are similarly reduced with atorvastatin 80 mg/d in men and women with recent
      stroke or TIA.

PMID- 18617660
TI  - Risk of stroke and myocardial infarction after reduction or cessation of
      cigarette smoking: a cohort study in korean men.
AB  - BACKGROUND AND PURPOSE: The effect of smoking reduction on cardiovascular disease
      outcomes has not been studied in Asian populations. METHODS: A total of 475 734
      Korean men aged 30 to 58 years, stratified into 9 groups based on smoking status
      at 2 different time points (1990 and 1992), were followed from 1992 to 2001 for
      the occurrence of stroke or myocardial infarction (MI) events. RESULTS: Compared
      with nonreducing heavy smokers (>/=20 cigarettes/d), those who quit smoking
      showed significantly lower risks of ischemic stroke, subarachnoid hemorrhage, and
      MI with hazard ratios (95% confidence intervals [CI]) of 0.66 (0.55 to 0.79),
      0.58 (0.38 to 0.90), and 0.43 (0.34 to 0.53), respectively. For hemorrhagic
      stroke, quitters showed lower risk compared with heavy smokers, but the
      difference was not statistically significant (hazard ratio 0.82, 95% CI: 0.64 to
      1.06). Compared with nonreducing heavy smokers, the risks of all stroke combined
      and MI among reducers tended to decrease, although the reductions were not
      statistically significant. The risks of subarachnoid hemorrhage and MI in those
      who reduced from moderate to light smoking tended to be lower than in nonreducing
      moderate (10 to 19 cigarettes/d) smokers. The association between the reduction
      of smoking level and the risk of stroke and MI did not change significantly when
      the analysis was limited to those whose smoking status in 1992 was maintained up
      to 1994. CONCLUSIONS: Smoking cessation was associated with a decrease in the
      risks of ischemic stroke, subarachnoid hemorrhage, and MI. More studies are
      needed to verify the likely health benefits of reducing smoking.

PMID- 18617659
TI  - Immediate clinical outcome of patients harboring unruptured intracranial
      aneurysms treated by endovascular approach: results of the ATENA study.
AB  - BACKGROUND AND PURPOSE: The management of unruptured intracranial aneurysms
      remains controversial and the results of endovascular treatment are not precisely
      known because no prospective data exist. The first prospective multicenter study
      (ATENA) was conducted in Canada and France to determine clinical outcome and
      risks of this treatment. METHODS: Six hundred forty-nine patients harboring a
      total of 1100 aneurysms from 27 Canadian and French neurointerventional centers
      were prospectively and consecutively treated by endovascular coil embolization.
      Of these, 739 unruptured intracranial aneurysms were treated during 700
      procedures. Aneurysms were selectively treated in the great majority of cases
      (98.4%) with coils alone (54.5%), the balloon remodeling technique (37.3%), or
      stenting (7.8%). RESULTS: Endovascular treatment failed in 32 aneurysms (4.3%).
      Technical adverse events with or without clinical modification were encountered
      in 15.4% of patients and included thromboembolic complications (7.1% per
      procedure), intraoperative rupture (2.6% per procedure), and device-related
      problems (2.9% per procedure). Adverse events associated with transient or
      permanent neurological deficit or death were encountered in 5.4% of cases. The 1
      month morbidity and mortality rates were 1.7% and 1.4%, respectively.
      CONCLUSIONS: Endovascular treatment of unruptured intracranial aneurysms is
      feasible in a high percentage of cases with low morbidity and mortality rates.

PMID- 18617662
TI  - Carotid intima media thickness and plaques can predict the occurrence of ischemic
      cerebrovascular events.
AB  - BACKGROUND AND PURPOSE: The clinical usefulness of noninvasive measurement of
      carotid intima media thickness and plaque visualization in the general population
      is still uncertain. METHODS: We evaluated the age-specific incidence rates of
      cerebrovascular events in a cohort of 1348 subjects randomly taken from the
      census list of San Daniele Township and followed for a mean period of 12.7 years.
      The association among common carotid intima media thickness, measured at
      baseline, arterial risk factors, and incidence of ischemic cerebrovascular events
      was modeled using Poisson regression. The predictive ability of common carotid
      intima media thickness over arterial risk factors (summarized in the Framingham
      Stroke Risk Score) was evaluated by receiver operating characteristic curve
      analysis. RESULTS: During the follow-up, 115 subjects developed nonfatal ischemic
      stroke, transient ischemic attack, or vascular death, which were the predefined
      study end points. After adjustment for age and sex, hypertension, diabetes,
      common carotid intima media thickness above 1 mm, and carotid plaques were all
      independent risk factors for development of vascular events. Inclusion of carotid
      findings (presence of common carotid intima media thickness above 1 mm or carotid
      plaques) resulted in a predictive power higher than Framingham Stroke Risk Score
      alone only on for those subjects with a Framingham Stroke Risk Score over 20%.
      CONCLUSIONS: Although common carotid intima media thickness and presence of
      carotid plaques are known to be risk factors for the development of vascular
      events and to be independent from the conventional risk factors summarized in the
      Framingham Stroke Risk Score, their contribution to individual risk prediction is
      limited. Further studies will be required to address the role of carotid
      ultrasonography in the primary prevention of high-risk subjects.

PMID- 18617661
TI  - Contralesional axonal remodeling of the corticospinal system in adult rats after
      stroke and bone marrow stromal cell treatment.
AB  - BACKGROUND AND PURPOSE: Motor recovery after stroke is associated with neuronal
      reorganization in bilateral hemispheres. We investigated contralesional
      corticospinal tract remodeling in the brain and spinal cord in rats after stroke
      and treatment of bone marrow stromal cells. METHODS: Adult male Wistar rats were
      subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered
      saline or bone marrow stromal cells were injected into a tail vein 1 day
      postischemia. An adhesive removal test was performed weekly to monitor functional
      recovery. Threshold currents of intracortical microstimulation on the left motor
      cortex for evoking bilateral forelimb movements were measured 6 weeks after
      stroke. When intracortical microstimulation was completed, biotinylated dextran
      amine was injected into the left motor cortex to anterogradely label the
      corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP
      and 614-mRFP were injected into left or right forelimb extensor muscles,
      respectively. All animals were euthanized 8 weeks after stroke. RESULTS: In
      normal rats (n=5), the corticospinal tract showed a unilateral innervation
      pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated
      that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb
      movement; 2) EGFP-positive pyramidal neurons were increased in the left intact
      cortex, which were labeled from the left stroke-impaired forelimb; and 3)
      biotinylated dextran amine-labeled contralesional axons sprouted into the
      denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3
      responses (n=8, P<0.05). CONCLUSIONS: Our data demonstrated that corticospinal
      tract fibers originating from the contralesional motor cortex sprout into the
      denervated spinal cord after stroke and bone marrow stromal cells treatment,
      which may contribute to functional recovery.

PMID- 18617663
TI  - Extent of hypoattenuation on CT angiography source images predicts functional
      outcome in patients with basilar artery occlusion.
AB  - BACKGROUND AND PURPOSE: Quantification of early ischemic changes (EIC) may
      predict functional outcome in patients with basilar artery occlusion (BAO). We
      tested the validity of a novel CT score, the posterior circulation Acute Stroke
      Prognosis Early CT score (pc-ASPECTS). METHODS: Pc-ASPECTS allots the posterior
      circulation 10 points. Two points each are subtracted for EIC in midbrain or pons
      and 1 point each for EIC in left or right thalamus, cerebellum or PCA-territory,
      respectively. We studied 2 different populations: (1) patients with suspected
      vertebrobasilar ischemia and (2) patients with BAO. We applied pc-ASPECTS to
      noncontrast CT (NCCT), CT angiography source images (CTASI), and follow-up image
      by 3-reader consensus. We calculated sensitivity for ischemic changes and
      analyzed the predictivity of pc-ASPECTS for independent (modified Rankin Scale
      [mRS] score </=2) and favorable (mRS score </=3) outcome. RESULTS: Of 130
      patients with suspected vertebrobasilar ischemia, 72% (94) had posterior
      circulation stroke, 8% (10) transient ischemic attack, and 20% (26) nonischemic
      etiology. Sensitivity for ischemic changes was improved with CTASI compared to
      NCCT (65% [95% CI, 57% to 73%] versus 46% [95% CI, 37% to 55%], respectively). Pc
      ASPECTS score on CTASI but not NCCT predicted functional independence (OR 1.58;
      P=0.005 versus 1.22; P=0.42, respectively). Of 46 patients with BAO, 52% (12/23)
      with CTASI pc-ASPECTS score >/=8 but only 4% (1/23) with a score <8 had favorable
      functional outcome (RR 12.1; 95% CI, 1.7 to 84.9). This difference was consistent
      in 21 patients with angiographic recanalization (RR 7.7; 95% CI, 1.1 to 52.1).
      CONCLUSIONS: The CTASI pc-ASPECTS score may identify BAO patients unlikely to
      have a favorable outcome despite recanalization.

PMID- 18617664
TI  - Factors that influence the stroke care team's effectiveness in reducing the
      length of hospital stay.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to explore the effects of a
      quality improvement program for improving stroke care and the determinants of
      success at the team and hospital levels. Method- For 16 months, 23
      multidisciplinary stroke service teams participated in a quality improvement
      collaborative designed to set up stroke services and reduce the length of
      hospital stay (LOHS). We monitored the LOHS and the discharge delay during the
      project and measured indicators of well organized stroke services at baseline and
      after the intervention. A multiple and multilevel regression model was used to
      relate the outcome variables to the team and hospital characteristics. National
      LOHS figures served as reference data. RESULTS: Data regarding 4549 stroke
      patients were included in the analyses. The LOHS decreased significantly from
      18.3 to 13.3 days. The mean LOHS varied substantially (9.2 to 20.9 days) after
      the intervention. Teams with higher team functioning scores showed lower LOHS
      scores and higher scores for the indicators of well organized stroke services.
      Team characteristics explain almost 40% of the variance in LOHS and 53% in the
      indicators of well organized stroke care. CONCLUSIONS: Participation in a
      national quality improvement collaborative effected a significant decrease of the
      LOHS and a significant increase in the presence of key features of stroke
      services. Variation in ability to reduce the LOHS and increase key features of
      stroke services were related to team functioning. The data suggest that the
      composite of team functioning is pivotal in quality-of-care improvement and may
      need specific attention in any quality improvement program.

PMID- 18617665
TI  - Practical model-based dose finding in early-phase clinical trials: optimizing
      tissue plasminogen activator dose for treatment of ischemic stroke in children.
AB  - BACKGROUND AND PURPOSE: A safe and effective tissue plasminogen activator (tPA)
      dose for childhood stroke has not been established. This article describes a
      Bayesian outcome-adaptive method for determining the best dose of an experimental
      agent and explains how this method was used to design a dose-finding trial for
      tPA in childhood. METHODS: The method assigns doses to successive cohorts of
      patients on the basis of each dose's desirability, quantified in terms of the
      tradeoff between efficacy and toxicity. The tradeoff function is constructed from
      several pairs of equally desirable (efficacy, toxicity) probabilities specified
      by the physicians planning the trial. Each cohort's dose is chosen adaptively,
      based on dose-outcome data from the patients treated previously in the trial, to
      optimize the efficacy-toxicity tradeoff. Application of the method to design the
      tPA trial is described, including a computer simulation study to establish design
      properties. A hypothetical cohort-by-cohort example is given to illustrate how
      the method works during trial conduct. RESULTS: Because only a dose that is both
      safe and efficacious may be selected and the method combines phase I and phase II
      by integrating efficacy and toxicity to choose doses, it avoids the more time
      consuming and expensive conventional approach of conducting a phase I trial based
      on toxicity alone followed by a phase II trial based on efficacy alone. This is
      especially useful in settings with low accrual rates, such as trials of tPA for
      pediatric acute ischemic stroke.

PMID- 18617667
TI  - Escalating levels of access to in-hospital care and stroke mortality.
AB  - BACKGROUND AND PURPOSE: Organized stroke care is an integrated approach to
      managing stroke to improve stroke outcomes by ensuring that optimal treatment is
      offered. However, limited information is available comparing different levels of
      organized care. Our aim was to determine whether escalating levels of organized
      care can improve stroke outcomes. METHODS: Cohort study including patients with
      acute ischemic stroke between July 2003 and March 2005 in the Registry of the
      Canadian Stroke Network (RCSN). The RCSN is the largest clinical database of
      patients with acute stroke patients seen at selected acute care hospitals in
      Canada. As stroke unit admission does not automatically imply receipt of
      comprehensive care, we created the organized care index to represent different
      levels of access to organized care ranging from 0 to 3 as determined by the
      presence of occupational therapy/physiotherapy, stroke team assessment, and
      admission to a stroke unit. The primary end point was early stroke mortality.
      Secondary end points include 30-day and 1-year mortality. RESULTS: Overall, 3631
      ischemic stroke patients were admitted to 11 hospitals. Seven day stroke
      mortality was 6.9% (249/3631), 30-day stroke mortality was 12.6% (457/3631), and
      1-year stroke mortality was 23.6% (856/3631). Risk-adjusted 7-day mortality was
      2.0%, 3.2%, 7.8%, and 22.5% for organized care index of 3, 2, 1, and 0. Higher
      level of care was associated with lower adjusted mortality (for organized care
      index 3, OR 0.03, 95% CI 0.02 to 0.07 for 7-day mortality; OR 0.09, 95% CI 0.05
      to 0.17 for 30-day mortality; and OR 0.40, 95% CI 0.25 to 0.64 for 1-year
      mortality). CONCLUSIONS: Higher level of access to care was associated with lower
      stroke mortality rates. Establishing a well-organized and multidisciplinary
      system of stroke care will help improve the quality of service delivered and
      reduce the burden of stroke.

PMID- 18617666
TI  - Cellular NAD replenishment confers marked neuroprotection against ischemic cell
      death: role of enhanced DNA repair.
AB  - BACKGROUND AND PURPOSE: NAD(+) is an essential cofactor for cellular energy
      production and participates in various signaling pathways that have an impact on
      cell survival. After cerebral ischemia, oxidative DNA lesions accumulate in
      neurons because of increased attacks by ROS and diminished DNA repair activity,
      leading to PARP-1 activation, NAD(+) depletion, and cell death. The objective of
      this study was to determine the neuroprotective effects of NAD(+) repletion
      against ischemic injury and the underlying mechanism. METHODS: In vitro ischemic
      injury was induced in rat primary neuronal cultures by oxygen-glucose deprivation
      (OGD) for 1 to 2 hours. NAD(+) was replenished by adding NAD(+) directly to the
      culture medium before or after OGD. Cell viability, oxidative DNA damage, and DNA
      base-excision repair (BER) activity were measured quantitatively up to 72 hours
      after OGD with or without NAD(+) repletion. Knockdown of BER enzymes was achieved
      in cultures using AAV-mediated transfection of shRNA. RESULTS: Direct NAD(+)
      repletion in neurons either before or after OGD markedly reduced cell death and
      OGD-induced accumulation of DNA damage (AP sites, single and double strand
      breaks) in a concentration- and time-dependent manner. NAD(+) repletion restored
      nDNA repair activity by inhibiting serine-specific phosphorylation of the
      essential BER enzymes AP endonuclease and DNA polymerase-beta. Knocking down AP
      endonuclease expression significantly reduced the prosurvival effect of NAD(+)
      repletion. CONCLUSIONS: Cellular NAD(+) replenishment is a novel and potent
      approach to reduce ischemic injury in neuronal cultures. Restoration of DNA
      repair activity via the BER pathway is a key signaling event mediating the
      neuroprotective effect of NAD(+) replenishment.

PMID- 18617668
TI  - Choline and creatine are not reliable denominators for calculating metabolite
      ratios in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Choline and creatine are commonly used as denominators
      for other metabolites in ischemic stroke spectroscopy, assuming that they do not
      change. We investigated their concentration variation over time after stroke.
      METHODS: Choline and creatine concentrations were measured by proton MR
      spectroscopic imaging in 51 patients at 5 times up to 3 months after stroke.
      RESULTS: Choline and creatine levels changed significantly in the ischemic
      region. Choline was significantly reduced during the first 2 weeks after stroke
      onset (P=0.034). Creatine was significantly reduced during the whole period of
      the study (P=0.011). CONCLUSIONS: Choline and creatine concentrations are not
      reliable denominators for metabolite ratios in acute stroke because their levels
      vary significantly in ischemic brain regions.

PMID- 18617669
TI  - Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in
      the rat.
AB  - BACKGROUND AND PURPOSE: Postsynaptic density-95 inhibitors reduce ischemic brain
      damage without inhibiting excitatory neurotransmission, circumventing the
      negative consequences of glutamatergic inhibition. However, their efficacy in
      permanent ischemia and in providing permanent neuroprotection and neurobehavioral
      improvement in a practical therapeutic window is unproven. These were tested here
      under conditions that included fever, which is a common occurrence in clinical
      stroke. METHODS: Six studies were performed in unfasted Sprague-Dawley rats. Two
      involved permanent pial vessel occlusion in male and female rats. Two involved
      permanent middle cerebral artery occlusion, which induced severe hyperthermia,
      and 2 involved transient middle cerebral artery occlusion. Animals were treated
      with a single intravenous injection of postsynaptic density-95 inhibitors (Tat
      NR2B9c([SDV]) or Tat-NR2B9c([TDV])) 1 hour or 3 hours after stroke. Infarct
      volumes and neurobehavior were assessed in a blinded manner at 24 hours (pial
      vessel occlusion and permanent middle cerebral artery occlusion) or at 62 days
      (transient middle cerebral artery occlusion). RESULTS: Postsynaptic density-95
      inhibitors dramatically reduced infarct size in male and female animals exposed
      to pial vessel occlusion (>50%), in hyperthermic animals with fever exceeding 39
      degrees C exposed to permanent middle cerebral artery occlusion (approximately
      50%), and at 62 days poststroke in animals exposed to transient middle cerebral
      artery occlusion (approximately 80%). Effectiveness of postsynaptic density-95
      inhibitors was achieved without the drugs affecting body temperature. In
      transient middle cerebral artery occlusion, a single dose of postsynaptic density
      95 inhibitor given 3 hours after stroke onset permanently maintained reduced
      infarct size and improved neurobehavior. CONCLUSIONS: Postsynaptic density-95
      inhibitors administrated 3 hours after stroke onset reduced infarct volumes and
      improved long-term neurobehavioral functions in a wide therapeutic window. This
      raises the possibility that they may have future clinical usefulness.

PMID- 18617670
TI  - Impact of anatomic features in the endovascular embolization of 181 anterior
      communicating artery aneurysms.
AB  - BACKGROUND AND PURPOSE: We analyzed the impact of detailed anatomic
      characteristics on the results of endovascular coil embolization for anterior
      communicating artery (AcoA) aneurysms and developed a predictive model estimating
      the probability of successful endovascular treatment. METHODS: One hundred eighty
      one AcoA aneurysms were treated with endovascular coil embolization between
      August 1991 and November 2005. Morphological characteristics that were analyzed
      included direction of the dome, location of the neck, association with hypoplasia
      or aplasia of AcoA complex vessels, sac, and neck size. Immediate clinical and
      anatomic results, long-term morbidity/mortality, recanalization rate, and delayed
      aneurysm thrombosis were analyzed. ORs were calculated for each anatomic and
      clinical result and logistic regression was used in formulating a predictive
      model. RESULTS: There were 115 females and 66 males. Age range was 9 to 86 years
      (mean 57). Factors significantly associated with complete embolization included
      small aneurysms (<10 mm), small neck (<4 mm), and anterior dome orientation.
      Factors significantly associated with aneurysm recanalization after long-term
      follow-up included aneurysm domes >10 mm, neck location on the AcoA, posterior
      dome orientation, and incomplete original embolization. Globally, the majority of
      patients remained neurologically intact or unchanged after the procedure (92.8%).
      Mortality was significantly influenced by the preoperative condition of the
      patient. The predictive model successfully represented the likely outcomes based
      on morphological features. CONCLUSIONS: AcoA aneurysm coil embolization can be
      safely performed with acceptable rates of morbidity. Dome and neck orientation,
      sack and neck size, sac-to-neck ratio, and associated anomalies should be
      considered to accurately assess the probability of successful treatment for AcoA
      aneurysms.

PMID- 18617671
TI  - The form and context of federalism: meanings for health care financing.
AB  - This article examines the meaning of federalism for health care financing (HCF)
      and is based on two considerations. First, federal institutions are embedded in
      their national context and interact with them. The design and performance of HCF
      policy will be influenced by contexts, the workings of the federal institutions,
      and the interactions of these institutions with different elements of the
      context. This article unravels these influences. Second, there is no unique model
      of federalism, and so we have to specify the particular form to which we refer.
      The examination of the influence of federalism and its context on HCF policy is
      facilitated by using a transnational comparative approach, and this article
      examines four mature federations: the United States, Australia, Canada, and
      Germany. The relatively poor performance of the U.S. HCF system seems associated
      with the fact that it operates in a context markedly less benign than those of
      the other national HCF systems. Heterogeneity of context appears also to have
      contributed to important differences between the United States and the other
      countries in the design of HCF policies. An analysis of how federalism works in
      practice suggests that, while U.S. federalism may be overall less favorable to
      the development of well-functioning HCF policies, the inferior performance of
      these policies is to be principally attributed to context.

PMID- 18617672
TI  - Health economists' views of health policy.
AB  - This article reports the views of a national survey of U.S. health economists on
      a series of questions ranging from mergers among health care providers to the
      profits of pharmaceutical manufacturers to fundamental health care reform. We
      find a high degree of agreement on issues of fact but considerable disagreement
      on issues that depend on values. Additional research may help to resolve some
      remaining disagreement about issues of fact but may do little to resolve
      disagreement over values. Results from this fall 2005 survey are compared with
      those from surveys conducted in 1989 and 1995.

PMID- 18617673
TI  - Administrative compensation of medical injuries: a hardy perennial blooms again.
AB  - Periods in which the costs of personal injury litigation and liability insurance
      have risen dramatically have often provoked calls for reform of the tort system,
      and medical malpractice is no exception. One proposal for fundamental reform made
      during several of these volatile periods has been to relocate personal injury
      disputes from the tort system to an alternative, administrative forum. In the
      medical injury realm, a leading incarnation of such proposals in recent years has
      been the idea of establishing specialized administrative "health courts." Despite
      considerable stakeholder and policy-maker interest, administrative compensation
      proposals have tended to struggle for broad political acceptance. In this
      article, we consider the historical experience of administrative medical injury
      compensation proposals, particularly in light of comparative examples in the
      context of workplace injuries, automobile injuries, and vaccine injuries. We
      conclude by examining conditions that may facilitate or impede progress toward
      establishing demonstration projects of health courts.

PMID- 18617674
TI  - Administrative "health courts" for medical injury claims: the federal
      constitutional issues.
AB  - Our article analyzes whether the federal government may constitutionally supplant
      a traditional system of common-law trials before state judges and juries with new
      federal institutions designed by statute for compensating victims of medical
      injuries. Specifically, this article examines the federal constitutional issues
      raised by various proposals to replace traditional medical malpractice litigation
      in state courts with a federal system of administrative "health courts." In doing
      so, we address the following constitutional issues: 1. Is there federal authority
      to preempt state law (the commerce clause and spending clause issues)? 2. May
      jurisdiction be created in non-article 3 tribunals, and may claims be decided
      without trial by jury (the separation of powers and Seventh Amendment issues)? 3.
      Would pilot programs that require some claims to be pursued in a federal
      administrative forum while other claimants are left to pursue traditional state
      tort law remedies be constitutional (the equal protection issue)? The article
      concludes that a federal compensation system through administrative health courts
      should be constitutional provided the statute is appropriately drafted and that
      appropriate factual findings are made concerning the benefits to patients and the
      public as well as to doctors and their insurers.

PMID- 18617675
TI  - Federal administrative health courts are unconstitutional: a reply to Elliott,
      Narayan, and Nasmith.
AB  - This commentary responds to the essay by Elliott, Narayan, and Nasmith wherein
      they propose that the federal government may preclude plaintiffs with medically
      inflicted injuries from bringing state common-law tort claims against those whose
      negligence caused their injury. The administrative system championed by Elliott
      and other proponents is a radical departure from the current civil justice
      system. Specifically, we argue that the administrative health courts, as
      proposed, violate the commerce clause, the spending clause, the Seventh
      Amendment, and separation of powers principles. The commentary concludes that
      such a system is fatally flawed and cannot withstand constitutional scrutiny.
      Moreover, we are not persuaded that Congress will be able to ground such a
      radical constitutional restructuring in any sound public policy, as the majority
      of studies do not evidence Elliott, Narayan, and Nasmith's presumption that the
      civil justice system has failed in the medical malpractice context.

PMID- 18617676
TI  - Comment on Marie Gottschalk's "Back to the future? Health benefits, organized
      labor, and universal health care".

PMID- 18617677
TI  - MUC1 mucin: a peacemaker in the lung.
AB  - MUC1 is a membrane-tethered mucin expressed on the surface of epithelial cells
      lining mucosal surfaces. Recent studies have begun to elucidate the physiologic
      function of MUC1 in the airways, pointing to an antiinflammatory role that is
      initiated late in the course of bacterial infection and is mediated through
      inhibition of TLR signaling. These new findings have great potential for clinical
      applications in controlling excessive and prolonged lung inflammation. This
      review briefly summarizes the protein structural features of MUC1 relevant to its
      function, the discovery of its antiinflammatory properties, and potential
      directions for future avenues of study.

PMID- 18617678
TI  - Adaptation of airway smooth muscle to basal tone: relevance to airway
      hyperresponsiveness.
AB  - Lung inflammation and airway hyperresponsiveness (AHR) are hallmarks of asthma,
      but their interrelationship is unclear. Excessive shortening of airway smooth
      muscle (ASM) in response to bronchoconstrictors is likely an important
      determinant of AHR. Hypercontractility of ASM could stem from a change in the
      intrinsic properties of the muscle, or it could be due to extrinsic factors such
      as chronic exposure of the muscle to inflammatory mediators in the airways. The
      latter could be the link between lung inflammation and AHR. The present study was
      designed to examine the influence of chronic exposure to a contractile agonist on
      the force-generating capacity of ASM. Force generation in response to electric
      field stimulation (EFS) was measured in ovine trachealis with or without a basal
      tone induced by acetylcholine (ACh). While the tone was maintained, the EFS
      induced force decreased transiently but increased over time to reach a plateau in
      approximately 50 minutes. The total force (ACh tone + EFS force) increased
      monotonically and in proportion to ACh concentration. The results indicate that
      the muscle adapted to the basal tone and regained its contractile ability in
      response to a second stimulus (EFS) over time. Analysis suggests that this is due
      to a cytoskeletal transformation that allows the cytoskeleton to bear force, thus
      freeing up actomyosin crossbridges to generate more force. Force adaptation in
      ASM as a consequence of prolonged exposure to the many spasmogens found in
      asthmatic airways could be a mechanism contributing to AHR seen in asthma.

PMID- 18617679
TI  - Regulation of COX-2 expression and IL-6 release by particulate matter in airway
      epithelial cells.
AB  - Particulate matter (PM) in ambient air is a risk factor for human respiratory and
      cardiovascular diseases. The delivery of PM to airway epithelial cells has been
      linked to release of proinflammatory cytokines; however, the mechanisms of PM
      induced inflammatory responses are not well-characterized. This study
      demonstrates that PM induces cyclooxygenase (COX)-2 expression and IL-6 release
      through both a reactive oxygen species (ROS)-dependent NF-kappaB pathway and an
      ROS-independent C/EBPbeta pathway in human bronchial epithelial cells (HBEpCs) in
      culture. Treatment of HBEpCs with Baltimore PM induced ROS production, COX-2
      expression, and IL-6 release. Pretreatment with N-acetylcysteine (NAC) or EUK
      134, in a dose-dependent manner, attenuated PM-induced ROS production, COX-2
      expression, and IL-6 release. The PM-induced ROS was significantly of
      mitochondrial origin, as evidenced by increased oxidation of the mitochondrially
      targeted hydroethidine to hydroxyethidium by reaction with superoxide. Exposure
      of HBEpCs to PM stimulated phosphorylation of NF-kappaB and C/EBPbeta, while the
      NF-kappaB inhibitor, Bay11-7082, or C/EBPbeta siRNA attenuated PM-induced COX-2
      expression and IL-6 release. Furthermore, NAC or EUK-134 attenuated PM-induced
      activation of NF-kappaB; however, NAC or EUK-134 had no effect on phosphorylation
      of C/EBPbeta. In addition, inhibition of COX-2 partly attenuated PM-induced
      Prostaglandin E2 and IL-6 release.

PMID- 18617680
TI  - Endogenous IL-11 signaling is essential in Th2- and IL-13-induced inflammation
      and mucus production.
AB  - IL-11 and IL-11 receptor (R)alpha are induced by Th2 cytokines. However, the
      role(s) of endogenous IL-11 in antigen-induced Th2 inflammation has not been
      fully defined. We hypothesized that IL-11, signaling via IL-11Ralpha, plays an
      important role in aeroallergen-induced Th2 inflammation and mucus metaplasia. To
      test this hypothesis, we compared the responses induced by the aeroallergen
      ovalbumin (OVA) in wild-type (WT) and IL-11Ralpha-null mutant mice. We also
      generated and defined the effects of an antagonistic IL-11 mutein on pulmonary
      Th2 responses. Increased levels of IgE, eosinophilic tissue and bronchoalveolar
      lavage (BAL) inflammation, IL-13 production, and increased mucus production and
      secretion were noted in OVA-sensitized and -challenged WT mice. These responses
      were at least partially IL-11 dependent because each was decreased in mice with
      null mutations of IL-11Ralpha. Importantly, the administration of the IL-11
      mutein to OVA-sensitized mice before aerosol antigen challenge also caused a
      significant decrease in OVA-induced inflammation, mucus responses, and IL-13
      production. Intraperitoneal administration of the mutein to lung-specific IL-13
      overexpressing transgenic mice also reduced BAL inflammation and airway mucus
      elaboration. These studies demonstrate that endogenous IL-11R signaling plays an
      important role in antigen-induced sensitization, eosinophilic inflammation, and
      airway mucus production. They also demonstrate that Th2 and IL-13 responses can
      be regulated by interventions that manipulate IL-11 signaling in the murine lung.

PMID- 18617681
TI  - IL-1 receptors mediate persistent, but not acute, airway hyperreactivity to ozone
      in guinea pigs.
AB  - Ozone exposure in the lab and environment causes airway hyperreactivity lasting
      at least 3 days in humans and animals. In guinea pigs 1 day after ozone exposure,
      airway hyperreactivity is mediated by eosinophils that block neuronal M(2)
      muscarinic receptor function, thus increasing acetylcholine release from airway
      parasympathetic nerves. However, mechanisms of ozone-induced airway
      hyperreactivity change over time, so that depleting eosinophils 3 days after
      ozone makes airway hyperreactivity worse rather than better. Ozone exposure
      increases IL-1beta in bone marrow, which may contribute to acute and chronic
      airway hyperreactivity. To test whether IL-1beta mediates ozone-induced airway
      hyperreactivity 1 and 3 days after ozone exposure, guinea pigs were pretreated
      with an IL-1 receptor antagonist (anakinra, 30 mg/kg, intraperitoneally) 30
      minutes before exposure to filtered air or to ozone (2 ppm, 4 h). One or three
      days after exposure, airway reactivity was measured in anesthetized guinea pigs.
      The IL-1 receptor antagonist prevented ozone-induced airway hyperreactivity 3
      days, but not 1 day, after ozone exposure. Ozone-induced airway hyperreactivity
      was vagally mediated, since bronchoconstriction induced by intravenous
      acetylcholine was not changed by ozone. The IL-1 receptor antagonist selectively
      prevented ozone-induced reduction of eosinophils around nerves and prevented
      ozone-induced deposition of extracellular eosinophil major basic protein in
      airways. These data demonstrate that IL-1 mediates ozone-induced airway
      hyperreactivity at 3 days, but not 1 day, after ozone exposure. Furthermore,
      preventing hyperreactivity was accompanied by decreased eosinophil major basic
      protein deposition within the lung, suggesting that IL-1 affects eosinophil
      activation 3 days after ozone exposure.

PMID- 18617683
TI  - Pheochromocytoma: current approaches and future directions.
AB  - Pheochromocytomas are rare catecholamine-secreting tumors that arise from
      chromaffin tissue within the adrenal medulla and extra-adrenal sites. Because of
      the excess secretion of hormones, these tumors often cause debilitating symptoms
      and a poor quality of life. While medical management plays a significant role in
      the treatment of pheochromocytoma patients, surgical excision remains the only
      cure. Improved medical management and surgical techniques and an increased
      understanding of hereditary disease have improved the outcome of pheochromocytoma
      patients with benign disease; however, the outcome of patients with malignant
      disease remains poor. In this review, we discuss the presentation, diagnosis,
      management, and future directions in the management of this disease.

PMID- 18617682
TI  - Identification of a cigarette smoke-responsive region in the distal MMP-1
      promoter.
AB  - Tobacco-related diseases are leading causes of death worldwide, and many are
      associated with expression of matrix metalloproteinase-1 (MMP-1). We have
      reported extracellular signal-regulated kinase (ERK)1/2-dependent induction of
      MMP-1 by cigarette smoke in lung epithelial cells. Our objectives were to define
      regions of the human MMP-1 promoter required for activation by smoke, to identify
      differences in responses of the 1G/2G -1607 polymorphic promoters to smoke, and
      to identify relevant transcription factors whose activity in airway epithelial
      cells is increased by smoke. The responses of deletion and mutant promoter
      constructs were measured in transfected cells during exposure to cigarette smoke
      extract (CSE). DNA oligonucleotide arrays were used to identify transcription
      factors activated after smoke exposure. CSE activated the MMP-1 promoter, and
      this induction was prevented by PD98059 blockade of ERK1/2 phosphorylation.
      Deletion studies revealed the distal 1kb promoter region (-4438 to -3280 upstream
      of the transcription start site) is essential for CSE induction of MMP-1, and
      confers activation of a minimal promoter. Studies of 1G and 2G MMP-1 polymorphic
      promoter variants revealed higher 2G allele basal and CSE-responsive activities
      than the 1G allele. Cotransfection, mithramycin, and electrophoretic mobility
      shift assay studies identified activating and repressive roles for Sp1 and PEA3
      transcription factors, respectively. Oligonucleotide DNA arrays confirmed
      activation of Sp1 and PEA3 by CSE. These data demonstrate that the MMP-1 promoter
      is a direct target of cigarette smoke in lung epithelial cells. This
      characterization of a smoke response region in the distal MMP-1 promoter has
      implications for smoking-related diseases such as cancer, heart disease, and
      emphysema.

PMID- 18617684
TI  - A reservoir of brown adipocyte progenitors in human skeletal muscle.
AB  - Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the
      control of energy balance in rodents. It has long been thought, however, that
      there is no physiologically relevant UCP1 expression in adult humans. In this
      study we show, using an original approach consisting of sorting cells from
      various tissues and differentiating them in an adipogenic medium, that a
      stationary population of skeletal muscle cells expressing the CD34 surface
      protein can differentiate in vitro into genuine brown adipocytes with a high
      level of UCP1 expression and uncoupled respiration. These cells can be expanded
      in culture, and their UCP1 mRNA expression is strongly increased by cell
      permeating cAMP derivatives and a peroxisome-proliferator-activated receptor
      gamma (PPARgamma) agonist. Furthermore, UCP1 mRNA was detected in the skeletal
      muscle of adult humans, and its expression was increased in vivo by PPARgamma
      agonist treatment. All the studies concerning UCP1 expression in adult humans
      have until now been focused on the white adipose tissue. Here we show for the
      first time the existence in human skeletal muscle and the prospective isolation
      of progenitor cells with a high potential for UCP1 expression. The discovery of
      this reservoir generates a new hope of treating obesity by acting on energy
      dissipation.

PMID- 18617685
TI  - In vivo osteoprogenitor potency of human stromal cells from different tissues
      does not correlate with expression of POU5F1 or its pseudogenes.
AB  - Expression of "stemness" markers is widely used as a predictor of stem cell
      properties of mesenchymal stem cells (MSC). Here, we show that bone marrow
      derived (BM)-MSC show stem cell-like behavior in vivo; that is, they form
      ossicles with formation of bone, formation of adipocytes, and establishment of
      the murine hematopoietic microenvironment. Multipotent umbilical vein-derived
      stromal cells (UVSC), on the other hand, do not form bone, nor do they give rise
      to adipocytes in vivo. Despite these differences in stem-cell-like behavior, BM
      MSC and UVSC express the two transcripts variants of POU5F1 at a similar level.
      Also, we found that in BM-MSC and UVSC, POU5F1 is detectable. However, more than
      89% of the POU5F1 transcripts correspond to the POU5F1P1, -P3, or -P4 pseudogene.
      Despite low-level expression of POU5F1, we were unable to precipitate POU5F1
      protein in either BM-MSC or UVSC. These results demonstrate that MSC stemness
      does not correlate to expression of POU5F1 transcripts or its pseudogenes.

PMID- 18617686
TI  - Chemoattractive activity of sonic hedgehog in the adult subventricular zone
      modulates the number of neural precursors reaching the olfactory bulb.
AB  - The adult subventricular zone (SVZ) supports neural stem cell self-renewal and
      differentiation and continually gives rise to new neurons throughout adult life.
      The mechanisms orienting the migration of neuroblasts from the SVZ to the
      olfactory bulb (OB) via the rostral migratory stream (RMS) have been extensively
      studied, but factors controlling neuroblast exit from the SVZ remain poorly
      explored. The morphogen Sonic Hedgehog (Shh) displays proliferative and survival
      activities toward neural stem cells and is an axonal chemoattractant implicated
      in guidance of commissural axons during development. We identify here the
      presence of Shh protein in SVZ extracts and in the cerebrospinal fluid of adult
      mice, and we demonstrate that migrating neuroblasts in the SVZ and RMS express
      the Shh receptor Patched. We show that Shh displays a chemoattractive activity in
      vitro on SVZ-derived neuronal progenitors, an effect blocked by Cur61414, a
      Smoothened antagonist. Interestingly, Shh-expressing cells grafted above the RMS
      of adult mice exert a chemoattractive activity on migrating neuroblasts in vivo,
      thus inducing their accumulation and deviation from their normal migratory
      pathway. Furthermore, the adenoviral transfer of Shh into the lateral ventricle
      or the blocking of Shh present in the SVZ of adult mice using its physiological
      antagonist Hedgehog interacting protein or neutralizing Shh antibodies provides
      in vivo evidence that Shh can retain SVZ-derived neuroblasts. The ability to
      modulate the number of neuroblasts leaving the SVZ and reaching the OB through
      the chemoattractive activity of Shh suggests a novel degree of plasticity in cell
      migration of this adult stem cell niche.

PMID- 18617687
TI  - Neural induction with neurogenin1 increases the therapeutic effects of
      mesenchymal stem cells in the ischemic brain.
AB  - Mesenchymal stem cells (MSCs) have been shown to ameliorate a variety of
      neurological dysfunctions. This effect is believed to be mediated by their
      paracrine functions, since these cells rarely differentiate into neuronal cells.
      It is of clinical interest whether neural induction of MSCs is beneficial for the
      replacement therapy of neurological diseases. Here we report that expression of
      Neurogenin1 (Ngn1), a proneural gene that directs neuronal differentiation of
      progenitor cells during development, is sufficient to convert the mesodermal cell
      fate of MSCs into a neuronal one. Ngn1-expressing MSCs expressed neuron-specific
      proteins, including NeuroD and voltage-gated Ca2+ and Na+ channels that were
      absent in parental MSCs. Most importantly, transplantation of Ngn1-expressing
      MSCs in the animal stroke model dramatically improved motor functions compared
      with the parental MSCs. MSCs with Ngn1 populated the ischemic brain, where they
      expressed mature neuronal markers, including microtubule associated protein 2,
      neurofilament 200, and vesicular glutamate transporter 2, and functionally
      connected to host neurons. MSCs with and without Ngn1 were indistinguishable in
      reducing the numbers of Iba1+, ED1+ inflammatory cells, and terminal
      deoxynucleotidyl transferase dUTP nick-end labeling(+) apoptotic cells and in
      increasing the numbers of proliferating Ki67+ cells. The data indicate that in
      addition to the intrinsic paracrine functions of MSCs, motor dysfunctions were
      remarkably improved by MSCs able to transdifferentiate into neuronal cells. Thus,
      neural induction of MSCs is advantageous for the treatment of neurological
      dysfunctions.

PMID- 18617689
TI  - IFATS collection: Using human adipose-derived stem/stromal cells for the
      production of new skin substitutes.
AB  - The ability to harvest and culture stem cell populations from various human
      postnatal tissues is central to regenerative medicine applications, including
      tissue engineering. The discovery of multipotent mesenchymal stem cells within
      the stromal fraction of adipose tissue prompted their use for the healing and
      reconstruction of many tissues. Here, we examined the influence of adipose
      derived stem/stromal cells (ASCs) on skin's regenerative processes, from a tissue
      engineering perspective. Using a self-assembly approach, human skin substitutes
      were produced. They featured a stromal compartment containing human extracellular
      matrix endogenously produced from either dermal fibroblasts or adipose-derived
      stem/stromal cells differentiated or not toward the adipogenic lineage. Human
      keratinocytes were seeded on each stroma and cultured at the air-liquid interface
      to reconstruct a bilayered skin substitute. These new skin substitutes,
      containing an epidermis and a distinctive stroma devoid of synthetic biomaterial,
      displayed characteristics similar to human skin. The influence of the type of
      stromal compartment on epidermal morphogenesis was assessed by the evaluation of
      tissue histology, the expression of key protein markers of the epidermal
      differentiation program (keratin [K] 14, K10, transglutaminase), the expression
      of dermo-epidermal junction components (laminins, collagen VII), and the presence
      of basement membrane and hemidesmosomes. Our findings suggest that adipose
      derived stem/stromal cells could usefully substitute dermal fibroblasts for skin
      reconstruction using the self-assembly method. Finally, by exploiting the
      adipogenic potential of ASCs, we also produced a more complete trilayered skin
      substitute consisting of the epidermis, the dermis, and the adipocyte-containing
      hypodermis, the skin's deepest layer. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 18617688
TI  - Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a
      mouse melanoma lung metastasis model.
AB  - Adult stem cells represent a potential source for cell-based therapy of cancer.
      The present study evaluated the potential of bone marrow-derived mesenchymal stem
      cells (MSC), genetically modified to express interferon (IFN)-alpha, for the
      treatment of lung metastasis in an immunocompetent mouse model of metastatic
      melanoma. A recombinant adeno-associated virus (rAAV) 6 vector encoding IFN-alpha
      was used to transduce mouse bone marrow-derived MSC ex vivo. Expression and
      bioactivity of the transgenic protein from rAAV-transduced MSC were confirmed
      prior to in vivo studies. A lung metastasis model of melanoma was developed by
      i.v. injection of B16F10 cells into 8-week-old C57BL/6 mice. Ten days later, MSC
      transduced with rAAV-IFN-alpha or green fluorescent protein were intravenously
      injected. One cohort of mice was sacrificed to determine the effects of the
      therapy at an earlier time point, and another cohort was observed for long-term
      survival. Results indicated that systemic administration of MSC producing IFN
      alpha reduced the growth of B16F10 melanoma cells and significantly prolonged
      survival. Immunohistochemistry analysis of the tumors from MSC-IFN-alpha-treated
      animals indicated an increase in apoptosis and a decrease in proliferation and
      blood vasculature. These data demonstrate the potential of adult MSC
      constitutively producing IFN-alpha to reduce the growth of lung metastasis in
      melanoma.

PMID- 18617690
TI  - An induction gene trap screen in neural stem cells reveals an instructive
      function of the niche and identifies the splicing regulator sam68 as a tenascin-C
      regulated target gene.
AB  - Neural stem cells (NSCs) reside in a niche that abounds in extracellular matrix
      (ECM) molecules. The ECM glycoprotein tenascin-C (Tnc) that occurs in more than
      25 isoforms represents a major constituent of the privileged NSC milieu. To
      understand its role for NSCs, the induction gene trap technology was successfully
      applied to mouse embryonic NSCs, and a library of more than 500 NSC lines with
      independent gene trap vector integrations was established. Our pilot screen
      identified Sam68 as a target of Tnc signaling in NSCs. The Tnc-mediated
      downregulation of Sam68, which we found expressed at low levels in the niche
      along with Tnc, was independently confirmed on the protein level. Sam68 is a
      multifunctional RNA-binding protein, and its potential significance for cultured
      NSCs was studied by overexpression. Increased Sam68 levels caused a marked
      reduction in NSC cell proliferation. In addition, Sam68 is a signal-dependent
      regulator of alternative splicing, and its overexpression selectively increased
      the larger Tnc isoforms, whereas a mutated phosphorylation-deficient Sam68
      variant did not. This emphasizes the importance of Sam68 for NSC biology and
      implicates an instructive rather than a purely permissive role for Tnc in the
      neural stem cell niche.

PMID- 18617691
TI  - Lentiviral-mediated HoxB4 expression in human embryonic stem cells initiates
      early hematopoiesis in a dose-dependent manner but does not promote myeloid
      differentiation.
AB  - The variation of HoxB4 expression levels might be a key regulatory mechanism in
      the differentiation of human embryonic stem cell (hESC)-derived hematopoietic
      stem cells (HSCs). In this study, hESCs ectopically expressing high and low
      levels of HoxB4 were obtained using lentiviral gene transfer. Quantification
      throughout differentiation revealed a steady increase in transcription levels
      from our constructs. The effects of the two expression levels of HoxB4 were
      compared regarding the differentiation potential into HSCs. High levels of HoxB4
      expression correlated to an improved yield of cells expressing CD34, CD38, the
      stem cell leukemia gene, and vascular epithelium-cadherin. However, no
      improvement in myeloid cell maturation was observed, as determined by colony
      formation assays. In contrast, hESCs with low HoxB4 levels did not show any
      elevated hematopoietic development. In addition, we found that the total
      population of HoxB4-expressing cells, on both levels, decreased in developing
      embryoid bodies. Notably, a high HoxB4 expression in hESCs also seemed to
      interfere with the formation of germ layers after xenografting into
      immunodeficient mice. These data suggest that HoxB4-induced effects on hESC
      derived HSCs are concentration-dependent during in vitro development and reduce
      proliferation of other cell types in vitro and in vivo. The application of the
      transcription factor HoxB4 during early hematopoiesis from hESCs might provide
      new means for regenerative medicine, allowing efficient differentiation and
      engraftment of genetically modified hESC clones. Our study highlights the
      importance of HoxB4 dosage and points to the need for experimental systems
      allowing controlled gene expression. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 18617692
TI  - Confounding between recombination and selection, and the Ped/Pop method for
      detecting selection.
AB  - In recent years, there have been major developments of population genetics
      methods to estimate both rates of recombination and levels of natural selection.
      However, genomic variants subject to positive selection are likely to have arisen
      recently and, consequently, had less opportunity to be affected by recombination.
      Thus, the two processes have an intimately related impact on genetic variation,
      and inference of either may be vulnerable to confounding by the other. We
      illustrate here that even modest levels of positive selection can substantially
      reduce population-based recombination rate estimates. We also show that genome
      wide scans to detect loci under recent selection in humans have tended to
      highlight loci in regions of low recombination, suggesting that confounding by
      recombination rate may have reduced the power of these studies. Motivated by
      these findings, we introduce a new genome-wide approach for detecting selection,
      based on the ratio of pedigree-based to population-based estimates of
      recombination rate. Simulations suggest that our "Ped/Pop" method, which is
      designed to capture completed sweeps, has good power to discriminate between
      neutral and adaptive evolution. Unusually for a multimarker method, our approach
      performs well in regions of high recombination and also has good power for many
      generations after the fixation of an advantageous variant. We apply the method to
      human HapMap and Perlegen data sets, finding confirmation of reported candidates
      as well as identifying new loci that may have undergone recent intense selection.

PMID- 18617693
TI  - Hypoxia-induced apelin expression regulates endothelial cell proliferation and
      regenerative angiogenesis.
AB  - Apelin has been identified as the endogenous ligand of the human orphan G protein
      coupled receptor APJ. This peptide exerts a variety of cardiovascular effects and
      particularly acts as an activator of angiogenesis. Importantly, hypoxia has been
      reported to regulate apelin expression but the molecular mechanism underlying
      hypoxia-induced apelin expression and the relationship with the physiological
      response of the apelin/APJ system are still not established. Here, we demonstrate
      that apelin expression is induced by hypoxia in cultured endothelial and vascular
      smooth muscle cells as well as in lung from mice exposed to acute hypoxia.
      Transient transfection experiments show that hypoxia-inducible transcriptional
      activation of apelin requires an intact hypoxia-responsive element (+813/+826)
      located within the first intron of the human apelin gene. Chromatin
      immunoprecipitation assay reveals that hypoxia-inducible factor-1alpha binds to
      the endogenous hypoxia-responsive element site of the apelin gene. Moreover,
      overexpression of hypoxia-inducible factor-1alpha increases the transcriptional
      activity of a reporter construct containing this hypoxia-responsive element,
      whereas small interfering RNA-mediated hypoxia-inducible factor-1alpha knockdown
      abolishes hypoxia-induced apelin expression. Finally, microinterfering RNA
      mediated apelin or APJ receptor knockdown inhibits both hypoxia-induced
      endothelial cell proliferation in vitro and hypoxia-induced vessel regeneration
      in the caudal fin regeneration of Fli-1 transgenic zebrafish. The hypoxia-induced
      apelin expression may, thus, provide a new mechanism involved in adaptive
      physiological and pathophysiological response of vascular cells to low oxygen
      level.

PMID- 18617694
TI  - Cardiovascular and hematopoietic defects associated with Notch1 activation in
      embryonic Tie2-expressing populations.
AB  - Notch signaling is critical for the development and maintenance of the
      cardiovasculature, with loss-of-function studies defining roles of Notch1 in the
      endothelial/hematopoietic lineages. No in vivo studies have addressed
      complementary gain-of-function strategies within these tissues to define
      consequences of Notch activation. We developed a transgenic model of Cre
      recombinase-mediated activation of a constitutively active mouse Notch1 allele
      (N1ICD(+)) and studied transgene activation in Tie2-expressing lineages. The in
      vivo phenotype was compared to effects of Notch1 activation on endothelial
      tubulogenesis, paracrine regulation of smooth muscle cell proliferation, and
      hematopoiesis. N1ICD(+) embryos showed midgestation lethality with defects in
      angiogenic remodeling of embryonic and yolk sac vasculature, cardiac development,
      smooth muscle cell investment of vessels, and hematopoietic differentiation.
      Angiogenic defects corresponded with impaired endothelial tubulogenesis in vitro
      following Notch1 activation and paracrine inhibition of smooth muscle cells when
      grown with Notch1-activated endothelial cells. Flow cytometric analysis of
      hematopoietic and endothelial precursor populations demonstrated a significant
      loss of CD71(+)/Ter119(+) populations with an active N1ICD(+) allele and a
      corresponding increase in c-Kit(+)/CD71 and Flk1(+) populations, suggesting a
      developmental block during the transition between c-Kit- and Ter119-expressing
      erythroblasts. Cardiovascular lineages are sensitive to an imbalance in Notch
      signaling, with aberrant activation reflecting a vascular phenotype comparable to
      a loss-of-function Notch1 mutation.

PMID- 18617695
TI  - Homotypic and endothelial cell adhesions via N-cadherin determine polarity and
      regulate migration of vascular smooth muscle cells.
AB  - Migration of smooth muscle cells from the arterial media to the intima is central
      to several vascular pathologies including restenosis. This study demonstrates
      that, like directional migration of other cells, smooth muscle migration is
      accompanied by a dramatic, polarized reorganization of the cell cytoskeleton that
      is accompanied by activation of the Rho GTPase Cdc42 and inactivation of glycogen
      synthase kinase-3beta. We also show, for the first time, that signals generated
      at the posterior-lateral aspects of wound edge cells by the cell-cell adhesion
      molecule N-cadherin are required for polarization and rapid migration of vascular
      smooth muscle. Importantly, when a cohort of migrating smooth muscle cells
      encounter CHO cells or the A10 smooth muscle cell line, neither of which
      expresses N-cadherin, polarity is only slightly suppressed. However, when smooth
      muscle cells encounter stably transfected, N-cadherin-expressing A10 cells or (N
      cadherin-expressing) vascular endothelium, they rapidly lose their polarized
      phenotype. The latter finding indicates that endothelial signaling to innermost
      smooth muscle cells via N-cadherin may be critical to normal vessel wall
      stability. We infer that asymmetrical distribution of N-cadherin is necessary for
      the establishment of cell polarity during migration and that N-cadherin ligation
      is highly effective in abrogating polarized migration. Finally, we showed that
      endothelial cell polarity does not depend on N-cadherin; therefore, this molecule
      may be an attractive target for therapies to prevent restenosis without
      suppressing endothelial repair and risking late thrombosis.

PMID- 18617696
TI  - Activation transcription factor-4 induced by fibroblast growth factor-2 regulates
      vascular endothelial growth factor-A transcription in vascular smooth muscle
      cells and mediates intimal thickening in rat arteries following balloon injury.
AB  - Activation transcription factor (ATF)-4 is a member of the ATF/CREB family of
      basic leucine zipper transcription factors that regulates cellular responses to a
      variety of stresses. The role of ATF-4 in smooth muscle cells of the vessel wall
      is completely unknown. Here, we show that ATF-4 expression is induced in smooth
      muscle cells in response to injury, both in vitro using a model of mechanical
      injury and in the media of balloon-injured rat carotid arteries. We demonstrate
      that ATF-4 is activated by fibroblast growth factor (FGF)-2, an injury-induced
      mitogen, through the phosphatidylinositol 3-kinase pathway. Injury also activates
      vascular endothelial growth factor (VEGF)-A, whose expression is stimulated by
      ATF-4 overexpression and exposure to FGF-2. FGF-2 induces ATF-4 binding to a
      recognition element located in the VEGF-A gene at +1767 bp and luciferase
      reporter gene expression dependent on this site. Moreover, ATF-4 knockdown with
      small interfering RNA or ATF-4 deficiency ameliorates FGF-2-inducible VEGF-A
      expression. Intraluminal delivery of ATF-4 small interfering RNA in rat carotid
      arteries blocks balloon injury-inducible ATF-4 and VEGF-A expression after 4
      hours and intimal thickening after 14 days. These findings reveal, for the first
      time, the induction of ATF-4 by both vascular injury and FGF-2. ATF-4 serves as a
      conduit for the inducible expression of 1 growth factor by another during the
      process of intimal thickening.

PMID- 18617697
TI  - Myeloperoxidase delays neutrophil apoptosis through CD11b/CD18 integrins and
      prolongs inflammation.
AB  - Polymorphonuclear neutrophil granulocytes have a central role in innate immunity
      and their programmed cell death and removal are critical for efficient resolution
      of acute inflammation. Myeloperoxidase (MPO), a heme protein abundantly expressed
      in neutrophils, is generally associated with killing of bacteria and oxidative
      tissue injury. Because MPO also binds to neutrophils, we investigated whether MPO
      could affect the lifespan of neutrophils. Here, we report that MPO independent of
      its catalytic activity through signaling via the adhesion molecule CD11b/CD18
      rescued human neutrophils from constitutive apoptosis and prolonged their life
      span. MPO evoked a transient concurrent activation of extracellular signal
      regulated kinase and Akt, leading to phosphorylation of Bad at both Ser112 and
      Ser136, prevention of mitochondrial dysfunction, and subsequent activation of
      caspase-3. Consistently, pharmacological inhibition of extracellular signal
      regulated kinase, Akt, or caspase-3 reversed the antiapoptosis action of MPO.
      Acute increases in plasma MPO delayed murine neutrophil apoptosis assayed ex
      vivo. In a mouse model of self-resolving inflammation, MPO also prolonged the
      duration of carrageenan-induced acute lung injury, as evidenced by enhanced
      alveolar permeability and accumulation of neutrophils parallel with suppression
      of neutrophil apoptosis. Our results indicate that MPO functions as a survival
      signal for neutrophils and thereby contribute to prolongation of inflammation.

PMID- 18617698
TI  - Update in female reproduction: a life-cycle approach.
AB  - CONTEXT: Female reproduction spans a developmental life arc from fetal life and
      childhood, through puberty to the reproductive years, and, finally, ovarian
      follicle depletion and the onset of menopause. OBJECTIVE: This invited review
      highlights a selection of reports from leading journals over the past 2 yr that
      have significantly advanced our understanding of female reproduction from
      conception to menopause. SYNTHESIS: During fetal life, in utero exposures may be
      important determinants of later pubertal and adult endocrine physiology.
      Epigenetic mechanisms are likely involved in the fetal programming of adult
      endocrine function. With regards to the polycystic ovary syndrome, recent
      clinical trials have confirmed the central role of clomiphene for ovulation
      induction in women with this disease. In addition, an expert panel has
      recommended that all women with polycystic ovary syndrome have a glucose
      tolerance test because of the high prevalence of impaired glucose tolerance in
      this population. In menopausal women the precise impact of estrogen therapy on
      cardiovascular biology remains to be delineated fully. Evolving data indicate
      that when initiated near the onset of menopause, estrogen therapy has fewer
      cardiovascular risks than when it is administered decades after the menopause.
      CONCLUSIONS: The essence of reproduction is the successful transmission of germ
      line DNA to a succeeding generation. Advances in genetics and endocrinology are
      converging to advance significantly our understanding of the biology of
      reproduction and our ability to influence reproductive processes. These advances
      will translate into new treatments for the prevalent medical problems of
      reproduction.

PMID- 18617699
TI  - Iodine in pregnancy: is salt iodization enough?

PMID- 18617700
TI  - Testosterone doping: dealing with genetic differences in metabolism and
      excretion.

PMID- 18617701
TI  - Insulin resistance and pubertal changes.

PMID- 18617702
TI  - Male hormonal contraception: so near and yet so far.

PMID- 18617703
TI  - Decreasing testosterone with increasing age: more factors, more questions.

PMID- 18617704
TI  - Lessons learned, rewards received.

PMID- 18617706
TI  - Peak flow values by gestation in women with asthma.
AB  - Asthma is one of the most common medical complications of pregnancy. Asthma
      control is associated with improved perinatal outcomes. Peak flow measures have
      been recommended to determine the status of asthma, yet norms for peak flow
      values in women with asthma are missing from the literature. The purpose of this
      study was to determine average peak flow values in pregnant women with asthma.
      Forty-three women were recruited into the study prior to the 20th week of
      pregnancy. Demographic data, including age, ethnic background, and number of
      pregnancies, were collected. Type and severity of asthma, medications used for
      asthma, and past hospitalizations for asthma were recorded. Peak flow values
      increased across the three trimesters. Significant differences were found in peak
      flow values between the first and third trimesters (>.001) and the second and
      third trimesters (>.007). Findings from the present study contradict those of
      studies on pregnant women without asthma.

PMID- 18617705
TI  - Denial and compliance in adults with asthma.
AB  - A descriptive study examining the relationship of denial of illness and
      compliance with inhaled controller asthma medications is conducted with 51 adults
      taking inhaled asthma controller medications. Affective and cognitive denial are
      assessed with the Levine Denial of Illness Scale. Severity is determined by
      portable spirometry; compliance is measured for 2 weeks with DOSER, a
      microelectronic monitor. The mean percent compliance rate for inhaled controller
      medications is 36%, with only 10.4% of the participants demonstrating optimal
      compliance (>80%). Although cognitive denial is not significantly associated with
      compliance, those in the suboptimal compliance group do have significantly higher
      information avoidance subscale scores (M = 1.88; p = .02). Affective denial is
      inversely correlated with compliance (r = -.31; p = .05) and is significantly
      higher in the suboptimal compliance group (M = 11.51; p =.05). These study
      findings suggest that affective denial may be a contributor to suboptimal
      compliance.

PMID- 18617707
TI  - Impact of telehealth on clinical outcomes in patients with heart failure.
AB  - The purpose of this randomized field study was to determine the effects of
      telehomecare on hospitalization, emergency department (ED) use, mortality, and
      symptoms related to sodium and fluid intake, medication use, and physical
      activity. The sample consists of 284 patients with heart failure. The authors
      used logistic regression to study the effects of telehomecare on health services
      utilization and mortality and a general linear model to analyze changes in self
      reported symptoms. On average, patients in the telehomecare groups had a lower
      probability of hospitalizations and ED visits than did patients in the control
      group. Differences were statistically significant at 60 days but not 120 days.
      Results show a greater reduction in symptoms for patients using telehomecare
      compared to control patients. The technology enables frequent monitoring of
      clinical indices and permits the home health care nurse to detect changes in
      cardiac status and intervene when necessary.

PMID- 18617708
TI  - Patients' perceptions of hospital discharge informational content.
AB  - Ensuring that patients' informational needs have been met prior to hospital
      discharge sets the stage for successful self-management of recovery at home. This
      secondary analysis study aims to identify differences in the amount of discharge
      teaching content needed and received by adult medical-surgical patients on the
      basis of their sociodemographic characteristics and hospitalization-related
      factors. The Quality of Discharge Teaching Scale (QDTS) is used to measure
      patients' perceptions of the amount of discharge-related informational content
      they needed and received. Eighty-nine percent of patients receive more
      informational content than they perceived they needed. Nonwhite patients report
      more content needed than White patients. Patients with prior hospitalizations and
      cardiac patients report greater amounts of content received. The QDTS content
      subscales provide a mechanism for assessing patient perceptions of discharge
      informational needs and discharge content received that can be used for clinical
      practice and quality monitoring.

PMID- 18617709
TI  - Care dependence: a struggle toward moments of respite.
AB  - The purpose of this study was to describe people's experiences of being dependent
      on others for care in their final stage of life, as well as what they felt made
      their experience of being dependent easier or more difficult. The
      phenomenological-hermeneutical method was chosen, where data collection consisted
      of open-ended interviews with nine people undergoing palliative care at a hospice
      unit or at home. The meaning of being care dependent is described via the
      following themes: changed relationship with oneself and with others, striving to
      adapt oneself to the situation, obstacles, and opportunities along the way while
      dependent. The result is described as an effort, a journey from independence to
      moments where it was possible to rest and recuperate while struggling with care
      dependency. Nursing staff require knowledge and understanding of experiences with
      care dependency to make life easier for people during increasing dependency in
      the final stage of life.

PMID- 18617711
TI  - Global models for the orientation field of fingerprints: an approach based on
      quadratic differentials.
AB  - Quadratic differentials naturally define analytic orientation fields on planar
      surfaces. We propose to model orientation fields of fingerprints by specifying
      quadratic differentials. Models for all fingerprint classes such as arches, loops
      and whorls are laid out. These models are parametrised by few, geometrically
      interpretable parameters which are invariant under Euclidean motions. We
      demonstrate their ability in adapting to given, observed orientation fields, and
      we compare them to existing models using the fingerprint images of the NIST
      Special Database 4. We also illustrate that these model allow for extrapolation
      into unobserved regions. This goes beyond the scope of earlier models for the
      orientation field as those are restricted to the observed planar fingerprint
      region. Within the framework of quadratic differentials we are able to verify
      analytically Penrose's formula for the singularities on a palm. Potential
      applications of these models are the use of their parameters as indices of large
      fingerprint databases, as well as the definition of intrinsic coordinates for
      single fingerprint images.

PMID- 18617710
TI  - Changes in family life perceived by mothers of young adult TBI survivors.
AB  - Little is known about changes in family life perceived by mothers of young adult
      survivors of a traumatic brain injury (TBI). A phenomenological method was used
      to describe the changes that seven mothers of TBI survivors perceived in family
      life 6 months or more after the TBI. The five basic changes in family life
      reported by mothers were: getting attention from each other for different reasons
      now, getting along with each other since the injury, facing new financial
      hurdles, going our separate ways down this new path, and splitting the family
      apart against our will. Compared to literature on stress and coping, the findings
      offered a unique perspective on changes in family life. Nurses can use the
      findings to initiate therapeutic conversations with mothers about changes in
      family life after a TBI.

PMID- 18617712
TI  - Design of multimodal dissimilarity spaces for retrieval of video documents.
AB  - This paper proposes a novel representation space for multimodal information,
      enabling fast and efficient retrieval of video data. We suggest describing the
      documents not directly by selected multimodal features (audio, visual or text),
      but rather by considering cross-document similarities relatively to their
      multimodal characteristics. This idea leads us to propose a particular form of
      dissimilarity space that is adapted to the asymmetric classification problem, and
      in turn to the query-by-example and relevance feedback paradigm, widely used in
      information retrieval. Based on the proposed dissimilarity space, we then define
      various strategies to fuse modalities through a kernel-based learning approach.
      The problem of automatic kernel setting to adapt the learning process to the
      queries is also discussed. The properties of our strategies are studied and
      validated on artificial data. In a second phase, a large annotated video corpus,
      (ie TRECVID-05), indexed by visual, audio and text features is considered to
      evaluate the overall performance of the dissimilarity space and fusion
      strategies. The obtained results confirm the validity of the proposed approach
      for the representation and retrieval of multimodal information in a real-time
      framework.

PMID- 18617713
TI  - Feature selection with kernel class separability.
AB  - Classification can often benefit from efficient feature selection. However, the
      presence of linearly nonseparable data, quick response requirement, small sample
      problem and noisy features makes the feature selection quite challenging. In this
      work, a class separability criterion is developed in a high-dimensional kernel
      space, and feature selection is performed by the maximization of this criterion.
      To make this feature selection approach work, the issues of automatic kernel
      parameter tuning, the numerical stability, and the regularization for multi
      parameter optimization are addressed. Theoretical analysis uncovers the
      relationship of this criterion to the radius-margin bound of the SVMs, the KFDA,
      and the kernel alignment criterion, providing more insight on using this
      criterion for feature selection. This criterion is applied to a variety of
      selection modes with different search strategies. Extensive experimental study
      demonstrates its efficiency in delivering fast and robust feature selection.

PMID- 18617714
TI  - Out-of-sample extrapolation of learned manifolds.
AB  - We investigate the problem of extrapolating the embedding of a manifold learned
      from finite samples to novel out-of-sample data. We concentrate on the manifold
      learning method called Maximum Variance Unfolding (MVU) for which the
      extrapolation problem is still largely unsolved. Taking the perspective of MVU
      learning being equivalent to Kernel PCA, our problem reduces to extending a
      kernel matrix generated from an unknown kernel function to novel points.
      Leveraging on previous developments, we propose a novel solution which involves
      approximating the kernel eigenfunction using Gaussian basis functions. We also
      show how the width of the Gaussian can be tuned to achieve extrapolation.
      Experimental results which demonstrate the effectiveness of the proposed approach
      are also included.

PMID- 18617715
TI  - Query by transduction.
AB  - There has been recently a growing interest in the use of transductive inference
      for learning. We expand here the scope of transductive inference to active
      learning in a stream-based setting. Towards that end this paper proposes Query-by
      Transduction (QBT) as a novel active learning algorithm. QBT queries the label of
      an example based on the p-values obtained using transduction. We show that QBT is
      closely related to Query-by-Committee (QBC) using relations between transduction,
      Bayesian statistical testing, Kullback-Leibler divergence, and Shannon
      information. The feasibility and utility of QBT is shown on both binary and multi
      class classification tasks using SVM as the choice classifier. Our experimental
      results show that QBT compares favorably, in terms of mean generalization,
      against random sampling, committee-based active learning, margin-based active
      learning, and QBC in the stream-based setting.

PMID- 18617716
TI  - Bittracker-a bitmap tracker for visual tracking under very general conditions.
AB  - This paper addresses the problem of visual tracking under very general
      conditions: a possibly non-rigid target whose appearance may drastically change
      over time; general camera motion; a 3D scene; and no a priori information except
      initialization. This is in contrast to the vast majority of trackers which rely
      on some limited model in which, for example, the target's appearance is known a
      priori or restricted, the scene is planar, or a pan tilt zoom camera is used.
      Their goal is to achieve speed and robustness, but their limited context may
      cause them to fail in the more general case. The proposed tracker works by
      approximating, in each frame, a PDF (probability distribution function) of the
      target's bitmap and then estimating the maximum a posteriori bitmap. The PDF is
      marginalized over all possible motions per pixel, thus avoiding the stage in
      which optical flow is determined. This is an advantage over other general-context
      trackers that do not use the motion cue at all or rely on the error-prone
      calculation of optical flow. Using a Gibbs distribution with respect to the first
      order neighborhood system yields a bitmap PDF whose maximization may be
      transformed into that of a quadratic pseudo-Boolean function, the maximum of
      which is approximated via a reduction to a maximum-flow problem. Many experiments
      were conducted to demonstrate that the tracker is able to track under the
      aforementioned general context.

PMID- 18617717
TI  - Inferring segmented dense motion layers using 5D tensor voting.
AB  - We present a novel local spatiotemporal approach to produce motion segmentation
      and dense temporal trajectories from an image sequence. A common representation
      of image sequences is a 3D spatiotemporal volume, (x,y,t), and its corresponding
      mathematical formalism is the fiber bundle. However, directly enforcing the
      spatiotemporal smoothness constraint is difficult in the fiber bundle
      representation. Thus, we convert the representation into a new 5D space
      (x,y,t,vx,vy) with an additional velocity domain, where each moving object
      produces a separate 3D smooth layer. The smoothness constraint is now enforced by
      extracting 3D layers using the tensor voting framework in a single step that
      solves both correspondence and segmentation simultaneously. Motion segmentation
      is achieved by identifying those layers, and the dense temporal trajectories are
      obtained by converting the layers back into the fiber bundle representation. We
      proceed to address three applications (tracking, mosaic, and 3D reconstruction)
      that are hard to solve from the video stream directly because of the segmentation
      and dense matching steps, but become straightforward with our framework. The
      approach does not make restrictive assumptions about the observed scene or camera
      motion and is therefore generally applicable. We present results on a number of
      data sets.

PMID- 18617718
TI  - Multiple-view geometry under the Linfinity-norm.
AB  - This paper presents a new framework for solving geometric structure and motion
      problems based on Linfinity-norm. Instead of using the common sum-of-squares cost
      function, that is, the L2-norm, the model-fitting errors are measured using the L
      norm. Unlike traditional methods based on L2, our framework allows for efficient
      computation of global estimates. We show that a variety of structure and motion
      problems, for example, triangulation, camera resectioning and homography
      estimation can be recast as quasi-convex optimization problems within this
      framework. These problems can be efficiently solved using Second-Order Cone
      Programming (SOCP) which is a standard technique in convex optimization. The
      methods have been implemented in Matlab and the resulting toolbox has been made
      publicly available. The algorithms have been validated on real data in different
      settings on problems with small and large dimensions and with excellent
      performance.

PMID- 18617719
TI  - Class-based feature matching across unrestricted transformations.
AB  - We develop a novel method for class-based feature matching across large changes
      in viewing conditions. The method is based on the property that when objects
      share a similar part, the similarity is preserved across viewing conditions.
      Given a feature and a training set of object images, we first identify the subset
      of objects that share this feature. The transformation of the feature's
      appearance across viewing conditions is determined mainly by properties of the
      feature, rather than of the object in which it is embedded. Therefore, the
      transformed feature will be shared by approximately the same set of objects.
      Based on this consistency requirement, corresponding features can be reliably
      identified from a set of candidate matches. Unlike previous approaches, the
      proposed scheme compares feature appearances only in similar viewing conditions,
      rather than across different viewing conditions. As a result, the scheme is not
      restricted to locally planar objects or affine transformations. The approach also
      does not require examples of correct matches. We show that by using the proposed
      method, a dense set of accurate correspondences can be obtained. Experimental
      comparisons demonstrate that matching accuracy is significantly improved over
      previous schemes. Finally, we show that the scheme can be successfully used for
      invariant object recognition.

PMID- 18617720
TI  - Randomized clustering forests for image classification.
AB  - Some of the most effective recent methods for content-based image classification
      work by quantizing image descriptors, and accumulating histograms of the
      resulting visual word codes. Large numbers of descriptors and large codebooks are
      required for good results and this becomes slow using k-means. We introduce
      Extremely Randomized Clustering Forests ensembles of randomly created clustering
      trees and show that they provide more accurate results, much faster training and
      testing, and good resistance to background clutter. Second, an efficient image
      classification method is proposed. It combines ERC-Forests and saliency maps very
      closely with the extraction of image information. For a given image, a classifier
      builds a saliency map online and uses it to classify the image. We show in
      several state-of-the-art image classification tasks that this method can speed up
      the classification process enormously. Finally, we show that the proposed ERC
      Forests can also be used very successfully for learning distance between images.
      The distance computation algorithm consists of learning the characteristic
      differences between local descriptors sampled from pairs of same or different
      objects. These differences are vector quantized by ERC-Forests and the similarity
      measure is computed from this quantization. The similarity measure has been
      evaluated on four very different datasets and always outperforms the state-of-the
      art competitive approaches.

PMID- 18617721
TI  - Effective proximity retrieval by ordering permutations.
AB  - We introduce a new probabilistic proximity search algorithm for range and K
      nearest neighbor (K-NN) searching in both coordinate and metric spaces. Although
      there exist solutions for these problems, they boil down to a linear scan when
      the space is intrinsically high-dimensional, as is the case in many pattern
      recognition tasks. This, for example, renders the K-NN approach to classification
      rather slow in large databases. Our novel idea is to predict closeness between
      elements according to how they order their distances towards a distinguished set
      of anchor objects. Each element in the space sorts the anchor objects from
      closest to farthest to it, and the similarity between orders turns out to be an
      excellent predictor of the closeness between the corresponding elements. We
      present extensive experiments comparing our method against state-of-the-art exact
      and approximate techniques, both in synthetic and real, metric and non-metric
      databases, measuring both CPU time and distance computations. The experiments
      demonstrate that our technique almost always improves upon the performance of
      alternative techniques, in some cases by a wide margin.

PMID- 18617722
TI  - Measuring spatiotemporal dependencies in bivariate temporal random sets with
      applications to cell biology.
AB  - Analyzing spatio-temporal dependencies between different types of events is
      highly relevant to numerous biological phenomena (e.g. signalling and
      trafficking) especially as advances in probes and microscopy have facilitated
      imaging of dynamic processes in living cells. For many types of events, the
      segmented areas can overlap spatially and temporally forming random clumps. In
      this paper, we model binary image sequences of two different event types as a
      realization of a bivariate temporal random set and propose a non-parametric
      approach to quantify spatial and spatio-temporal interrelations using the pair
      correlation, cross-covariance and the Ripley IK functions. Based on these summary
      statistics we propose a randomization procedure to test independence between
      event types by applying random toroidal shifts and Monte Carlo tests. A
      simulation study assessed the performance of the proposed estimators and showed
      that these statistics capture the spatio-temporal dependencies accurately. The
      estimation of the spatio-temporal interval of interactions was also obtained. The
      method was successfully applied to analyze the interdependencies of several
      endocytic proteins using image sequences of living cells and validated the
      procedure as a new way to automatically quantify dependencies between proteins in
      a formal and robust manner.

PMID- 18617723
TI  - Principal component analysis based on l1-norm maximization.
AB  - A method of principal component analysis (PCA) based on a new L1-norm
      optimization technique is proposed. Unlike conventional PCA which is based on L2
      norm, the proposed method is robust to outliers because it utilizes L1-norm which
      is less sensitive to outliers. It is invariant to rotations as well. The proposed
      L1-norm optimization technique is intuitive, simple, and easy to implement. It is
      also proven to find a locally maximal solution. The proposed method is applied to
      several datasets and the performances are compared with those of other
      conventional methods.

PMID- 18617732
TI  - Biochemical evaluation of patients with active acromegaly and type 2 diabetes
      mellitus: efficacy and safety of the galanin test.
AB  - The oral glucose tolerance test, which is considered the gold standard for the
      diagnosis of active acromegaly, should not be performed in the presence of basal
      hyperglycemia. Moreover, false-positive responses may occur in patients with
      diabetes mellitus. Galanin has previously been demonstrated to induce paradoxical
      inhibition of growth hormone (GH) secretion in most patients with active
      acromegaly. In this study, we assessed GH response to galanin infusion in a
      series of 17 consecutive patients with active acromegaly, 7 of whom had
      coexistent type 2 diabetes mellitus and 10 were without either diabetes mellitus
      or impaired tolerance to glucose. 6 acromegalic patients with diabetes mellitus
      (85.7%) and 7 without diabetes (70.0%) showed a decrease in serum GH values
      during galanin infusion (chi2 0.9; p = 0.6). The GH nadir occurred at a
      comparable time in the two groups of acromegalic patients. Moreover, the two
      groups showed no significant difference (p = 0.45) in DeltaGH during galanin
      infusion. Galanin infusion did not induce any significant change in plasma
      glucose levels in both diabetic and non-diabetic patients with acromegaly. The
      results of our study provide evidence that the galanin test may be of value for
      the diagnosis of acromegaly in patients with type 2 diabetes mellitus.

PMID- 18617733
TI  - Ramadan fasting and the GH/IGF-1 axis of trained men during submaximal exercise.
AB  - AIMS: The aim of this study was to explore possible changes in body composition,
      blood glucose regulation, plasma growth hormone (GH), insulin-like growth factor
      1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), and insulin
      concentrations of trained athletes in response to the intermittent fasting and
      dehydration of Ramadan observance. METHODS: Nine trained male rugby players (age
      19 +/- 2 years, height 1.78 +/- 0.74 m) were tested 3 times: before Ramadan (C),
      at the end of the first week (R1), and during the fourth week (R2). They
      performed a progressive cycle ergometer test at each visit. The work rate was
      increased in 6-min stages corresponding to 20, 30, 40, 50 and 60% of W max.
      Substrate oxidation was evaluated by indirect calorimetry. On each occasion,
      substrate and plasma hormone concentrations were measured at rest and at the end
      of the exercise. RESULTS: Ramadan fasting induced a significant decrease in body
      mass and body fat (R2 vs. C, p < 0.001). Plasma concentrations of glucose,
      insulin, GH, IGF-1 and IGFBP-3 did not change significantly between C and R2,
      either at rest or following exercise. CONCLUSION: Ramadan fasting induces
      positive changes in body composition without disturbing glucose regulation or
      activity of the GH/IGF-1 system.

PMID- 18617734
TI  - Relation of Trp64Arg polymorphism of beta 3-adrenergic receptor gene to
      adipocytokines and fat distribution in obese patients.
AB  - BACKGROUND/AIM: Obesity has multiple causes and is determined by the interaction
      between genetic and environmental factors. A genetic factor is a (Trp64Arg)
      missense mutation in the beta 3-adrenergic receptor. The aim of our study was to
      investigate the influence of Trp64Arg polymorphism in the beta 3-adrenergic
      receptor gene on weight, adipocytokines, insulin resistance, and fat distribution
      in obese patients. METHODS: A population of 217 nondiabetic obese Caucasian
      outpatients was analyzed. Indirect calorimetry and tetrapolar bioimpedance
      results, blood pressure, nutritional intake with 3-day food records, and
      biochemical parameters were evaluated. The genotype of beta 3-adrenergic receptor
      gene polymorphism (Trp64Arg) was studied. RESULTS: The mean age of the patients
      was 44.3 +/- 16.4 years, and the mean body mass index was 35.2 +/- 5.2. One
      hundred and eighty-six patients (52 males and 134 females; 85.8%) had the
      genotype Trp64/Trp64 (wild-type group), and 31 patients (11 males and 20 females;
      14.2%) had the genotype Trp64/Arg64 (mutant group). In the mutant group, body
      mass index, weight, fat mass, waist-to-hip ratio, waist circumference, and C
      reactive protein levels were higher than in the wild-type group. The
      adipocytokine levels were similar in both groups. CONCLUSION: The patients of the
      mutant group (Trp64/Arg64) had higher body mass index, weight, waist
      circumference, fat mass, waist-to-hip ratio, and C-reactive protein values than
      those of the wild-type group.

PMID- 18617735
TI  - Absolute quantification in proton magnetic resonance spectroscopy is superior to
      relative ratio to discriminate Alzheimer's disease from Binswanger's disease.
AB  - BACKGROUND/AIMS: Although many proton magnetic resonance spectroscopy studies
      have assessed the relative ratios of brain metabolites from patients with
      dementia, absolute quantification is rare. The aim of this study is to compare
      the diagnostic accuracy of these 2 methods in proton magnetic resonance
      spectroscopy in discriminating Alzheimer's disease (AD) and Binswanger's disease
      (BD) from healthy controls (HC). METHODS: The subjects were 30 AD patients, 13 BD
      patients and 26 HC subjects. Single-voxel proton MR spectra at short echo times
      were acquired from 8 volumes of interest. RESULTS: At 80% specificity, the
      absolute N-acetylaspartate concentration in the hippocampus was the most
      sensitive measure to discriminate AD from HC, and the absolute N-acetylaspartate
      concentration in the anterior periventricular and deep white matter to
      differentiate BD from HC and AD. No relative ratio using creatine as a reference
      had a sensitivity over 80% at 80% specificity. The cause of disparities between
      the 2 methods was attributed to fluctuations in the creatine concentration.
      CONCLUSION: Our study revealed that absolute quantification is superior to
      relative ratio to differentiate AD and BD from HC.

PMID- 18617736
TI  - Asymmetrical dimethylarginine is increased in plasma and decreased in
      cerebrospinal fluid of patients with Alzheimer's disease.
AB  - BACKGROUND: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of
      nitric oxide (NO) synthase and may alter NO production during pathological
      conditions. Concerning Alzheimer's disease (AD), there are reports on altered
      cerebral NO metabolism, but only few studies on ADMA concentrations in plasma and
      cerebrospinal fluid (CSF). METHODS: We assessed plasma ADMA in 80 AD patients and
      80 age- and gender-matched controls and CSF ADMA in a subgroup of 53 AD patients
      and 20 controls. RESULTS: ADMA plasma concentrations were increased, while CSF
      ADMA concentrations were decreased in AD patients. There was a significant
      association between decreasing CSF ADMA levels and the severity of cognitive
      impairment. CONCLUSION: Elevated ADMA in plasma might be a contributing factor
      for AD through alterations of NO metabolism, for example decreased cerebral
      microperfusion, while decreased levels of CSF ADMA might lead to a cerebral
      increase of NO, peroxynitrite production and oxidative protein damage. Our study
      reveals different mechanisms of plasma and CSF ADMA regulation, both potentially
      contributing to AD pathology.

PMID- 18617737
TI  - Prediction of institutionalisation in dementia. A systematic review.
AB  - BACKGROUND/AIMS: In the past decades, a substantial number of studies considered
      factors influencing institutionalisation of persons with dementia. This study
      reviews recent work on predictors of actual institutionalisation in dementia.
      METHOD: Relevant articles were identified by a systematic search of the
      literature. Studies were considered which included persons aged 65 and over, and
      whose results were based on prospective design and on multivariate statistical
      analyses. RESULTS: Forty-two studies were identified. The rate of
      institutionalisation increased from 20% in the first year after diagnosis to 50%
      after 5 years. Median time to institutionalisation was estimated between 30 and
      40 months. Predictors of institutionalisation were classified according to a
      provided conceptual framework in the categories sociodemographic and relationship
      characteristics of persons with dementia and caregivers, primary stressors,
      secondary stressors and resources. CONCLUSION: The overview of research
      activities in this area showed a lack of methodological strength in a large part
      of identified studies. Nevertheless, a lot of well-examined and less highlighted
      predictors could be identified.

PMID- 18617738
TI  - Magnetic resonance imaging in frontotemporal dementia shows subcortical atrophy.
AB  - BACKGROUND/AIMS: The clinical syndrome of the frontotemporal dementias (FTD)
      overlaps with frontal-subcortical circuit syndromes. We explored the extent to
      which subcortical atrophy on structural magnetic resonance imaging may indicate a
      subcortical contribution to the progression of FTD. METHODS: This cross-sectional
      case-control study compared striatal and thalamic gray matter volumes and
      functional levels from 30 FTD cases and 30 age- and gender-matched controls.
      RESULTS: The FTD group had significantly more atrophy in all gray matter
      subcortical regions, correlating with ipsilateral frontocortical atrophy.
      Subcortical atrophy was also associated with functional disability. Subcortical
      asymmetry was most marked in subjects with primary progressive aphasia.
      CONCLUSION: Subcortical gray matter atrophy may contribute as significantly to
      symptoms of FTD as cortical atrophy.

PMID- 18617739
TI  - The association between APOE genotype and memory dysfunction in subjects with
      mild cognitive impairment is related to age and Alzheimer pathology.
AB  - BACKGROUND: Memory problems are a main feature of mild cognitive impairment (MCI)
      and may be related to the apolipoprotein E (APOE) epsilon4 allele. We
      investigated whether the effect of the APOE genotype on memory in subjects with
      MCI was dependent on age and underlying Alzheimer disease (AD) pathology.
      METHODS: Subjects with MCI (n = 180) were selected from a memory clinic setting.
      Subjects with at least one APOE epsilon4 allele (n = 83) were compared to non
      carriers on several memory measures. Subjects were reassessed 5-10 years later in
      order to identify those who developed AD. RESULTS: In the middle-aged subgroup,
      the APOE epsilon4 allele was most strongly related to decreased subjective
      organization and in the old subgroup to a decreased delayed recall. After
      excluding subjects with incipient AD (n = 33), results remained similar in the
      middle-aged subgroup, but in the old subgroup the APOE genotype was no longer
      associated with memory dysfunction. CONCLUSION: The presence of the APOE epsilon4
      allele is associated with impaired memory functioning in both middle-aged and old
      subjects with MCI, although the memory function affected varies with age. Its
      effect on memory function may be dependent on underlying AD pathology in elderly
      subjects, but not in middle-aged subjects.

PMID- 18617741
TI  - Clinicopathologic findings of colorectal traditional and sessile serrated
      adenomas in Korea: a multicenter study.
AB  - BACKGROUND/AIMS: Serrated polyps have emerged as important evidence supporting
      the serrated polyp-neoplasia pathway in colorectal carcinogenesis, an alternate
      to the classical adenoma-carcinoma sequence. However, there is confusion over the
      diagnostic criteria for serrated polyps including traditional serrated adenoma
      (TSA) and sessile serrated adenoma (SSA). In addition, clinical and pathologic
      characteristics of each are largely unknown and need further exploration.
      METHODS: The 753 polyps that were previously diagnosed as serrated adenoma (SA)
      from 14 tertiary care university hospitals in Korea between 2003 and 2005 were
      evaluated for the clinicopathologic findings of TSA and SSA. RESULTS: Among 753
      cases, 420 (55.8%) were reclassified as TSA and 56 (7.4%) as SSA. Among the
      pathologic parameters, crypt branching, crypt dilatation, and horizontal crypts
      were more frequent in SSA than in TSA (p < 0.001). SSA was larger than TSA (12.6
      +/- 7.3 vs. 9.8 +/- 6.9 mm, p = 0.005), was more likely to be flat type (p =
      0.006), and was more frequently located in the proximal colorectum (p = 0.012).
      There were no significant differences in age, sex, and body mass index between
      TSA and SSA. CONCLUSIONS: Locationand endoscopic features of the polyps with
      abnormal crypt morphology in histologic findings could be helpful for the
      diagnosis and classification of SAs.

PMID- 18617740
TI  - Predictive value of rapid decline in mini mental state examination in clinical
      practice for prognosis in Alzheimer's disease.
AB  - BACKGROUND: Given the poorer prognosis of Alzheimer's disease (AD) patients with
      rapid cognitive decline (RCD), there is a need for a clinical assessment tool to
      detect these patients. OBJECTIVE: To investigate if there is a Mini Mental State
      Examination (MMSE) threshold of decline during 6 months of follow-up which
      predicts a worse disease progression at the 2-year follow-up. Then, to propose a
      feasible definition of RCD for routine clinical practice. METHODS: Data from 565
      community-dwelling AD patients recruited in a multi-centre prospective
      observational study were assessed. All patients had MMSE scores between 10 and 26
      at inclusion and were followed up 6-monthly using a standardised clinical
      assessment. Patients were classified as rapid and non-rapid decliners according
      to 2 MMSE decline thresholds tested: >or=3 points and >or=4 points for decline
      over the first 6 months of the study. Worse disease outcome was defined as
      attainment of 1 of 4 clinical end points 18 months later: institutionalisation,
      death, increased physical dependence or worsening of behavioural and
      psychological symptoms. RESULTS: 135 patients (23.9%) lost >or=3 points during
      the first 6 months of follow-up in the MMSE score and 77 patients (13.6%) lost
      >or=4 points. Patients with moderate disease and a loss of >or=4 points showed a
      significantly increased risk of mortality (HR = 5.6, 95% CI 2.0-15.9) and
      institutionalisation (HR = 3.8, 95% CI 1.8-8.1) at the 2-year follow-up. The same
      MMSE threshold was associated with a higher risk of physical decline (HR = 1.6,
      95% CI 1.2-2.3). CONCLUSION: The loss of >or=4 points in MMSE during the first 6
      months of follow-up seems to be a predictor of worse clinical course, and thus it
      could be used to define the category of AD patients presenting a RCD.

PMID- 18617742
TI  - Pepsin detection in the sputum/saliva for the diagnosis of gastroesophageal
      reflux disease in patients with clinically suspected atypical gastroesophageal
      reflux disease symptoms.
AB  - BACKGROUND/AIMS: Atypical manifestations of gastroesophageal reflux disease
      (GERD) are diverse. We aimed to determine whether pepsin detection in the
      sputum/saliva could be useful for diagnosing GERD in patients with clinically
      suspected atypical GERD symptoms. METHODS: Patients with clinically suspected
      atypical GERD symptoms provided sputum/saliva collected before bedtime, at the
      time of those symptoms, and after awakening for pepsin measurement by Western
      blot analysis. All subjects received 24-hour esophageal pH monitoring, and then
      40 mg of esomeprazole was given twice a day for 2 weeks. RESULTS: The pepsin test
      was positive in 20 out of 40 patients, with pepsin detected mainly in the samples
      collected at the time of symptoms (45%). Samples collected from healthy
      volunteers (n = 8) were all negative for pepsin. 24-hour pH-metry was positive in
      9 patients (23%). Based on 24-hour pH-metry data, the sensitivity and negative
      predictive value of the pepsin test were excellent in most of typical and
      atypical symptom groups, whereas its specificity and positive predictive value
      were relatively low, particularly in atypical symptom groups. CONCLUSIONS: Pepsin
      measurement in the sputum/saliva collected at the time of symptoms provides a
      sensitive, non-invasive method for diagnosing GERD in patients with clinically
      suspected atypical GERD symptoms.

PMID- 18617743
TI  - Maintenance treatment for GERD: residual symptoms are associated with
      psychological distress.
AB  - AIM: The aim of this study was to explore determinants of residual reflux
      symptoms among patients with gastroesophageal reflux disease (GERD) despite
      maintenance treatment with acid suppressive medication (ASM). METHODS: Primary
      care GERD patients on chronic ASM were classified as symptom-free (55%) or
      symptomatic (45%) according to the impact of their residual reflux symptoms
      (QolRad). They were compared with respect to lifestyle (BMI, alcohol, smoking,
      physical exercise), compliance (daily ASM dosage), disease history, psychological
      factors (SCL-90) and quality of life (SF-36). RESULTS: None of the investigated
      lifestyle factors, nor dosage and disease history were related to residual
      symptoms. However, symptomatic patients differed from patients with relief on all
      psychological and quality of life dimensions. In a multiple logistic regression
      model somatization, hostility, mental health, body pain, as well as gender were
      independently associated with residual symptoms; the derived ROC curve had an AUC
      of 0.78. CONCLUSIONS: The majority of GERD patients is symptom-free on chronic
      ASM; they display a healthy psychological state and high quality of life.
      Residual symptoms however, are associated with psychological distress and lower
      quality of life. Recognition of this subgroup might hold the key to improving
      long-term management of gastroesophageal reflux.

PMID- 18617744
TI  - Skin cancers arising in tattoos: coincidental or not?
AB  - Trauma, scars and/or chronic inflammation have been reported as underlying causes
      of skin cancers in occasional cases. Tattooing is a traumatizing procedure
      characterized by the introduction of exogenous pigment in the dermis by
      puncturing the skin. Even though cases of malignancies such as melanoma, basal
      cell carcinomas, squamous cell carcinomas and keratoacanthomas have been reported
      for the past 40 years, it remains unclear what role tattoos play in their
      pathogenesis. We report here 2 new cases and wish to discuss the arguments and
      counter-arguments for such a potential relationship.

PMID- 18617745
TI  - Osteopathic treatment of patients with chronic non-specific neck pain: a
      randomised controlled trial of efficacy.
AB  - OBJECTIVE: Chronic non-specific neck pain (CNP) is a common, often disabling
      condition which still lacks a reliable therapeutic standard. Empiric evidence
      suggests that osteopathic interventions might be effective in alleviating CNP
      symptoms. A randomized controlled clinical trial of efficacy was performed to
      test this hypothesis. MATERIALS AND METHODS: 135 CNP sufferers were identified
      through advertisements, and 41 patients who met all relevant predefined criteria
      were recruited. All participants received a 12-min session of sham ultrasound
      once a week for an average of 10 weeks. In addition, a test-dependent osteopathic
      intervention of 45 min was given to 24 participants every other week. 40
      participants could be followed up for 12 weeks after the end of therapy. The main
      outcome parameter was pain intensity measured on a numeric rating scale (NRS,
      range: 0-10). RESULTS: There were 2 dropouts in the intervention group and 2 in
      the control group. Average pain intensity decreased from 4.7 to 2.2 in the
      osteopathic group (p < 0.0005), and from 4.8 to 4.0 in the control group (p =
      0.09). The intergroup difference of longitudinal changes was clearly significant,
      too (p = 0.02). Further slight but comparable reductions were observed at follow
      up (0.3 and 0.4 NRS points, respectively). These changes seem to have a positive
      impact on quality of life, as assessed by generic and specific instruments such
      as the MOS SF-36 and the Northwick Park Pain Questionnaire. CONCLUSIONS: A series
      of test-dependent osteopathic interventions may be a promising therapeutic
      regimen for CNP sufferers. Further studies will have to demonstrate a) whether
      these findings are reproducible, and b) whether positive long-term outcomes can
      be achieved.

PMID- 18617746
TI  - Socio-demographic characteristics and health perceptions among male and female
      visitors to CAM practitioners in a total population study.
AB  - BACKGROUND: The aim was to explore the prevalence of visitors to CAM
      practitioners in a total population with reference to sex, self-rated health
      status and socio-demographic characteristics. METHODS: The paper reports findings
      from the Nord-Trondelag Health Study (HUNT 2), a total population-based health
      survey of 42,277 respondents conducted in central Norway who answered questions
      on visits to a CAM practitioner. Variables included were age, marital status,
      education, receiving social welfare benefits, lifestyle (daily smoker), Hospital
      Anxiety and Depression Scale (HADS-T), self-rated health status, and having a
      limiting chronic complaint. RESULTS: Some 12.8% (95% CI 12.5-13.1) of the
      population had visited a CAM practitioner in the last 12 months, with females
      visiting almost twice as often as males. Multivariate analysis showed that
      consulting a CAM practitioner was significantly associated in both sexes with
      being middle-aged (male age 40-49 OR 1.6 (1.2-2.0), female age 30-39 OR 1.4 (1.1
      1.6)); poor self-rated health status (male OR 5.1 (3.1-8.5), female 3.9 (2.2-6.8
      )); and reporting a chronic complaint (male OR 1.5 (1.3-1.8), female OR 1.4 (1.2
      1.6)). Daily smoking of cigarettes was associated with a decreased likelihood for
      visiting a CAM practitioner (male OR 0.7 (0.6-0.9), female OR 0.8 (0.7-0.9)). In
      females, both a higher total HADS-T score (score >20 OR 1.5 (1.2-2.0)) and middle
      level education (OR 1.2 (1.1-1.4)) were associated with visiting a CAM
      practitioner. CONCLUSIONS: Visitors to CAM practitioners had lower self-reported
      health than non-users, but socio-demographic variables did not discriminate
      between users and non-users.

PMID- 18617747
TI  - Characterization of proteases, proteins, and eicosanoid-like substances in
      soluble extracts from allergenic pollen grains.
AB  - BACKGROUND: Pollen is an important trigger of seasonal rhinitis, conjunctivitis,
      and/or allergic asthma, and an exacerbating factor in atopic dermatitis. Pollen
      grains contain allergen proteins, enzymes, and bioactive lipid mediators, the
      latter two possibly involved in the pathogenesis of allergic diseases through IgE
      independent mechanisms. METHODS: We analyzed the patterns of release of
      endopeptidases from allergenic pollen of Japanese cedar, Japanese cypress, and
      Rocky mountain juniper, which belong to the Cupressaceae/Taxodiaceae family, and
      birch, ragweed, and two grasses, Kentucky blue and cultivated rye, using
      synthetic substrates, class-specific inhibitors, and zymography. The proteins
      released were analyzed by gel electrophoresis. Eicosanoid-like substances were
      measured by enzyme-linked immunosorbent assays for prostaglandin E(2) and
      leukotriene B(4). RESULTS: Major fractions of proteins, eicosanoid-like
      substances, and at least one molecular species of serine endopeptidase were
      released into phosphate-buffered saline from the pollen grains at 37 degrees C
      within 25 min or 60 min without sonication. In the Cupressaceae/Taxodiaceae
      family, sonication was necessary for the release of other proteins and another
      serine endopeptidase. In birch, ragweed, and the grasses, most of the serine and
      cysteine endopeptidases were released without sonication. Proteases released
      within 25 min digested gelatin and/or casein differently among plant species.
      CONCLUSIONS: Grains of allergenic pollen release proteases, which can digest not
      only short synthetic substrates but also protein substrates, along with
      eicosanoid-like substances and proteins. The release of these components could
      contribute to the formation of a microenvironment optimum for initiation of the
      sensitization or the exacerbation of pollen allergy in tissues exposed to pollen
      grains.

PMID- 18617748
TI  - Mal d 2, the thaumatin-like allergen from apple, is highly resistant to
      gastrointestinal digestion and thermal processing.
AB  - BACKGROUND: The stability of food allergens to proteolysis and thermal
      denaturation contributes considerably to their allergenicity. METHODS: Mal d 2,
      an allergenic thaumatin-like protein (TLP) from apple, was isolated and purified
      by anion exchange chromatography. Its IgE reactivity was tested by ELISA and
      immunoblotting using sera from apple allergic patients. The proteolytic stability
      of Mal d 2 was investigated using two in vitro digestion models. Effects of
      thermal treatment at different pH values on the secondary structure of the
      protein were recorded by circular dichroism. The level and IgE reactivity of Mal
      d 2 present in industrially prepared foods were assessed. RESULTS: Purified Mal d
      2 consisted of two isoforms. Both harbored carbohydrate moieties and bound serum
      IgE from apple allergic individuals. Mal d 2 showed remarkable stability to
      proteolysis and thermal treatments. The allergen remained intact after 2 h each
      of gastric and subsequent duodenal digestion retaining its full IgE-binding
      capacity. Mal d 2 was unfolded at neutral and acidic pH at 70 degrees C.
      Refolding after cooling was only observed at acidic pH. Mal d 2 detected by an
      anti-TLP antibody in cloudy apple juice did not bind IgE of a serum pool of apple
      allergic patients. CONCLUSION: Our findings suggest that Mal d 2 maintains its
      structure in the gastrointestinal tract, a feature essential for sensitizing the
      mucosal immune system and provoking allergic reactions.

PMID- 18617749
TI  - Experimental rhinovirus infection increases human tissue kallikrein activation in
      allergic subjects.
AB  - BACKGROUND: Rhinovirus infection is a major cause of asthma exacerbations. While
      rhinovirus infection is known to generate kinins in the upper respiratory track,
      little is known about the effect of rhinovirus on kinin generation in the lower
      airway. We previously identified human tissue kallikrein (hTK) as the principal
      lung kininogenase during allergic airway inflammation. In this report we
      investigate the effect of experimental rhinovirus infection on hTK activity in
      the airways of atopic subjects with and without asthma. METHODS: Eight atopic
      subjects, 4 with asthma, underwent bronchoscopy with lavage. At least 1 month
      later, subjects were inoculated with rhinovirus, then underwent repeat
      bronchoscopy with lavage 4 and 18 days later. hTK mRNA was measured in nasal
      scrape samples by quantitative real-time PCR. hTK activity (chromogenic substrate
      assay) and IL-8 levels (ELISA) were assessed in the bronchoalveolar lavage fluid.
      RESULTS: At day 4 after rhinovirus inoculation, nasal hTK mRNA was modestly
      increased in both the rhinitis (1.7-fold) and asthmatic (2.1-fold) groups. A
      doubling or greater increase in hTK activity after rhinovirus infection was
      observed in all 4 asthmatic subjects (mean 19-fold increase) but only in 1 of 4
      atopic subjects without asthma (mean 2-fold increase). Rhinovirus infection also
      increased the IL-8 protein level in bronchoalveolar lavage fluid, which
      correlated with hTK activity (R = 0.82). CONCLUSION: Experimental rhinovirus
      infection in allergic asthmatic subjects is accompanied by increased lower airway
      hTK activation, which parallels the appearance of IL-8. Rhinovirus-induced hTK
      activation may contribute to airway inflammation and asthmatic exacerbations.

PMID- 18617750
TI  - Induction of shrimp tropomyosin-specific hypersensitivity in mice.
AB  - BACKGROUND: Shellfish hypersensitivity is amongst the most common food allergies.
      The major shellfish allergen was identified as tropomyosin. Here, we investigated
      the immediate hypersensitivity responses, IgE and cell-mediated immune response
      in mice sensitized with recombinant shrimp tropomyosin. METHODS: Shrimp
      tropomyosin was cloned and expressed as a His-tagged fusion recombinant protein
      in Escherichia coli. Three- to 4-week-old BALB/c mice were sensitized by
      intragastric administration of recombinant tropomyosin (0.1 mg) plus cholera
      toxin (10 mug) on days 0, 12, 19 and 26 and challenged on day 33. Mice fed with
      phosphate-buffered saline plus cholera toxin were included as controls. Animals
      were monitored for immediate hypersensitive responses and tropomyosin-specific
      IgE over time. In addition, shrimp tropomyosin-specific CD4+ T cells, interleukin
      4 and interferon-gamma levels were determined from in vitro splenocyte cultures.
      A passive cutaneous anaphylaxis assay was also conducted. RESULTS: Mice fed with
      shrimp tropomyosin developed swelling of the snout, increased scratching behavior
      and shrimp tropomyosin-specific IgE. Sera from tropomyosin-sensitized mice
      elicited vascular leakage in naive mice in the passive cutaneous anaphylaxis
      assay. Shrimp tropomyosin-specific CD4+ T cell proliferations and elevated
      interleukin-4 over interferon-gamma levels were evident in splenocyte cultures of
      tropomyosin-fed mice upon tropomyosin stimulation. In contrast, shrimp
      tropomyosin-specific IgE, CD4+ T cells and hypersensitive responses were absent
      in the control mice. CONCLUSION: We have generated a BALB/c model of shrimp
      allergy. This model provides a useful tool for evaluating the immunopathogenic
      mechanisms involved in shellfish hypersensitivity.

PMID- 18617751
TI  - Peroxisome proliferator-activated receptor alpha is crucial for iloprost-induced
      in vivo angiogenesis and vascular endothelial growth factor upregulation.
AB  - We have previously demonstrated that iloprost, a stable prostacyclin (PGI(2))
      analogue, induces angiogenesis in vivo, through a vascular endothelial growth
      factor (VEGF)-dependent mechanism. In this study, we demonstrate that iloprost
      induced angiogenesis and VEGF upregulation are modulated by peroxisome
      proliferator-activated receptor-alpha (PPARalpha), a ligand-inducible
      transcription factor that belongs to the nuclear hormone receptor superfamily and
      plays multiple biological activities in the vascular system. We show that
      iloprost is unable to induce angiogenesis in mice lacking the PPARalpha gene
      (PPARalpha-/- mice). Likewise, iloprost-induced VEGF upregulation is absent in
      PPARalpha-/- mice. In contrast, iloprost induces a robust angiogenic response in
      wild-type mice, along with local upregulation of VEGF. Importantly, mice lacking
      the PPARalpha gene exhibit a normal angiogenic response to VEGF, indicating that
      the absence of PPARalpha does not result in a general impairment of angiogenesis,
      but specifically affects the ability of iloprost to induce angiogenesis. Our data
      demonstrate unexpected functional relationships between the PGI(2) system and the
      PPAR signaling pathway and shed new light on the molecular mechanisms involved in
      iloprost-induced angiogenesis.

PMID- 18617752
TI  - Predictability of intraocular lens calculation using the Holladay II formula
      after in-the-bag or optic captured posterior chamber intraocular lens
      implantation in paediatric cataracts.
AB  - PURPOSE: To assess the predictability of postoperative refraction using the
      Holladay II-formula in paediatric patients randomized to undergo 2 different
      surgical procedures. METHODS: Fourty cataractous eyes of 29 patients (age 2.31
      11.75 years) were operated with in-the-bag intraocular lens implantation.
      Randomly, either an anterior vitrectomy (group A, 19 eyes) or posterior optic
      capture without vitrectomy (group B, 21 eyes) was performed. Randomization was
      done in 4 separate age groups, in accordance with 4 target refractions (0, 1, 2
      and 3 dpt) to compensate for the anticipated myopic shift. RESULTS: The predicted
      refraction correlated with the achieved postoperative refraction (total group, p
      = 0.019), closer in group A (p = 0.033) than in group B (p = 0.265); however, the
      results of groups A and B were not significantly different (p = 0.324). There was
      a tendency for postoperative targeted hyperopia being underachieved in the
      youngest patients. CONCLUSION: The Holladay II formula provides reliable
      intraocular lens calculation in paediatric cataracts. The tendency to
      underachieve the target refraction in younger patients needs further
      investigation.

PMID- 18617753
TI  - Clinical and experimental research of corneal lymphangiogenesis after
      keratoplasty.
AB  - The objective of this study is to provide further evidence that corneal
      lymphangiogenesis occurs after keratoplasty, and to explore the association of
      corneal hemangiogenesis, corneal inflammation and transplantation history with
      corneal lymphangiogenesis. Rat corneal lymphangiogenesis was examined by electron
      microscopy, lymphatic vessel endothelial receptor (LYVE-1) immunohistochemistry,
      and whole-mount immunofluorescence at 1, 3, 7, 10 and 14 days after corneal
      transplantation. Blood and lymphatic vessels in human transplanted corneas were
      identified by LYVE-1 and CD(31) immunohistochemistry, then the association
      between corneal blood vessel counting, inflammatory index and transplantation
      history with the lymphatic vessel counting was examined. The results showed that
      corneal lymphangiogenesis was present in all rat corneas and 26% of human
      transplanted corneas. Lymphatic vessel counting was significantly associated with
      blood vessel counting, inflammatory index and transplantation history (all p
      values <0.0001). We conclude that corneal lymphangiogenesis develops after
      keratoplasty, and is strongly associated with hemangiogenesis, inflammation and
      the history of transplantation.

PMID- 18617754
TI  - Foveolitis associated with dengue Fever: a case series.
AB  - BACKGROUND: Dengue fever (DF), a viral infection caused by dengue virus, is
      characterized by fever, headache, muscle and joint pains. Approximately 50-100
      million people are infected annually. Ocular manifestations during DF are
      uncommon and include intraretinal hemorrhages and cotton wool spots;
      manifestations predominantly characterized by foveal involvement have not been
      described before in DF or any other retinopathies. We describe the clinical
      features of a series of patients with DF-associated foveolitis. METHODS: A
      retrospective review of patients with maculopathy associated with DF was
      conducted. Patients found to have a yellow-orange lesion at the fovea, supported
      by a typical optical coherence tomography (OCT) finding of disruption of the
      outer neurosensory retina, were analyzed. RESULTS: Ten eyes of 6 patients were
      studied. The mean age was 19.8 years. The mean presenting best corrected visual
      acuity was 6/45 (range of 6/7.5 to counting fingers). Fundus examination revealed
      a yellow-orange lesion at the fovea which corresponded to outer neurosensory
      retina disruption on OCT. Multifocal electroretinography showed decreased foveal
      and parafoveal responses. Treatment was variable, depended on visual acuity and
      ranged from observation to immunosuppression. CONCLUSION: Foveolitis may be
      associated with DF. OCT is a useful tool for the diagnosis and monitoring of
      progression of this condition.

PMID- 18617756
TI  - Aqueous humor and serum levels of chromium in cataract patients with and without
      diabetes mellitus.
AB  - PURPOSE: To evaluate the aqueous humor and serum levels of chromium (Cr) in
      cataract patients with and without diabetes mellitus. METHODS: Levels of Cr were
      measured using atomic absorption spectrometry in the serum from 20 patients and
      aqueous humor aspirates taken during anterior segment surgery from 20 eyes of 20
      patients who had diabetic cataracts and from 20 eyes of 20 patients who had
      senile cataract only. RESULTS: The mean aqueous humor Cr concentration in eyes
      with diabetes cataract was significantly lower than that from eyes with senile
      cataract (p < 0.001). There was also a statistically significant difference
      between the serum Cr concentrations of the diabetic group and the control group
      (p < 0.001). CONCLUSION: The aqueous humor and serum Cr levels are decreased in
      eyes with diabetic cataract.

PMID- 18617755
TI  - Early clinical experience with ranibizumab for occult and minimally classic
      neovascular membranes in age-related macular degeneration.
AB  - BACKGROUND: In large randomized multicenter trials, ranibizumab has shown its
      therapeutic efficacy for exudative age-related macular degeneration (AMD). The
      aim of this paper is to report the real-life clinical experience with this
      treatment for occult and minimally classic membranes without pigment epithelium
      detachment. METHODS: We conducted a retrospective chart review of 37 patients
      with occult and minimally classic neovascular membranes in AMD, without pigment
      epithelium detachment. RESULTS: The mean visual improvement of 2 lines at 3, 6
      and 9 months corresponds well with the results of the large trials. A mean number
      of 5 reinjections was reached by month 8. It may potentially exceed the mean 5.5
      injections of the PrONTO study (prospective optical coherence tomography imaging
      of patients with neovascular AMD treated with intraocular ranibizumab). At months
      6-8 recurrence was frequently observed. CONCLUSION: The early experience of
      ranibizumab in clinical practice brings similarly good results as the large-scale
      trials. However, interrupting the treatment too early may be a disadvantage.

PMID- 18617757
TI  - Assessment of an effective visual field testing strategy for a normal pediatric
      population.
AB  - AIM: To investigate which visual field testing strategy yields more reliable and
      tolerable field analysis in a normal pediatric population. MATERIAL AND METHODS:
      68 healthy children aged 6-13 years with no ocular or systemic diseases were
      included in the study. One randomly selected eye of each child underwent standard
      achromatic visual field analysis using a Model 750 Humphrey Field Analyzer II
      (Carl Zeiss Meditec, Dublin, Calif., USA). We evaluated the reliability criteria
      (false negative, false positive and fixation loss scores) and the duration of the
      visual field tests performed by Fastpac (with stimulus sizes III and V,
      respectively) and SITA Fast with stimulus size III. Moreover, subjects underwent
      Goldmann perimetry testing with stimulus V. Ability to complete the perimetry
      tests was also scored. Perimetric analysis was stopped before the end if signs of
      fatigue appeared. Mean sensitivity, mean defect and pattern standard deviation
      were recorded for automated tests. RESULTS: All subjects but 8 successfully
      completed each of four tests. The mean duration of the tests was 4.23, 5.46, 6.35
      and 11.06 min for SITA Fast with stimulus size III, Fastpac with stimulus size V,
      Size III and Goldmann perimetry, respectively (p < 0.001). Both false-negative
      and false-positive test scores were found to be significantly lower for SITA Fast
      with stimulus size III compared to the other automated tests (p < 0.01). Children
      older than 8 years (n = 35) achieved significantly higher test reliability scores
      (p < 0.01). CONCLUSION: As early detection of structural and functional visual
      abnormalities may be of utmost importance in the pediatric population considering
      many potentially serious neurological and ocular problems met with, accurate and
      reproducible visual field testing is vital. To achieve this goal, visual field
      testing with SITA Fast algorithm seemed to be a promising strategy for a
      pediatric population in a typical clinical setting.

PMID- 18617758
TI  - This issue at a glance.

PMID- 18617759
TI  - [Problems faced by Korean patients with chronic liver disease and the role of the
      Korean Association for the Study of the Liver--emphases on social discrimination,
      insufficiency of reimbursement coverage, and deficiency of the welfare system].

PMID- 18617760
TI  - [The relation between hepatic venous pressure gradient and complications of liver
      cirrhosis].

PMID- 18617761
TI  - [Physiologic and pathologic experimental models for studying cholangiocytes].
AB  - Cholangiocytes (epithelial cells lining the intra- and extrahepatic bile ducts)
      and hepatocytes are two major components of liver epithelia. Although
      cholangiocytes are less numerous than hepatocytes, they are involved in both bile
      secretion and diverse cellular processes such as cell-cycle phenomena, cell
      signaling, and interactions with other cells, matrix components, foreign
      organisms, and xenobiotics. Cholangiocytes are also targets in several human
      diseases including cholangiocarcinoma, primary sclerosing cholangitis, autoimmune
      cholangitis, and vanishing bile-duct syndrome. The rapid advances in experimental
      biology technologies are greatly expanding interest in and knowledge of the
      physiology and pathophysiology of cholangiocytes. This review focuses on the
      progress of in vivo and in vitro experimental models in elucidating the
      physiologic functions of cholangiocytes and the pathophysiology of various
      cholangiopathies. The following aspects are reviewed: isolation of cholangiocytes
      from the liver and their heterogeneity, various culture systems, establishment of
      cholangiocyte cell lines, isolation and usage of intrahepatic bile-duct units,
      three-dimensional modeling of the bile duct, experimental models for inducing
      cholangiocyte proliferation, and various cholangiopathies such as
      cholangiocarcinoma, primary sclerosing cholangitis, and autoimmune cholangitis.

PMID- 18617763
TI  - [Serum hyaluronic acid level: correlation with quantitative measurement of
      hepatic fibrosis in a cirrhotic rat model].
AB  - BACKGROUNDS/AIMS: The serum level of hyaluronic acid (HA) has been suggested as a
      useful serologic marker for hepatic fibrosis. However, the relationship between
      serum HA levels and quantitative markers of fibrosis from liver tissue has not
      been reported. The aim of this study was to determine the correlation between
      serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic
      rat model. METHODS: Cirrhosis was produced by common bile duct ligation (BDL) in
      adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1,
      sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks
      (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed
      histomorphologically using the Batts and Ludwig scoring system. Serum HA level
      and hepatic hydroxyproline content were quantified. The gene expressions in the
      liver of procollagen, collagen, and transforming growth factor-beta (TGF-beta)
      were measured by reverse transcriptase-polymerase chain reaction. RESULTS: In
      groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean+/-SD) were 0, 1.3+/
      0.5, 2.6+/-0.5, and 3.4+/-0.5, respectively (P<0.05), serum HA levels were 12.5+/
      3.2, 30.0+/-4.3, 228.6+/-157.7, and 391.3+/-207.7 ng/mL (P<0.05), and the
      concentration of hydroxyproline was 12.4+/-2.8, 17.6+/-3.8, 17.9+/-2.4, and
      33.4+/-3.4 microg/g liver tissue, and it was significantly higher in group G4
      than in the other groups (P<0.05). The gene expressions of collagen, procollagen,
      and TGF-beta1 in the liver were also significantly higher in group G4 compared
      with the other groups (P<0.05). Direct linear correlations were observed between
      serum HA level and hepatic hydroxyproline content, hepatic gene expressions of
      collagen, procollagen, TGF-beta1, and histomorphological grade of hepatic
      fibrosis (P<0.001). CONCLUSIONS: These results indicate that serum HA is a useful
      and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis.

PMID- 18617762
TI  - [Measurement of hepatic venous pressure gradient in liver cirrhosis: relationship
      with the status of cirrhosis, varices, and ascites in Korea].
AB  - BACKGROUND/AIMS: The relationships between the hepatic venous pressure gradient
      (HVPG) and the status of cirrhosis, complications of portal hypertension and the
      severity of cirrhosis are not clear. The aim of this study was to determine the
      relationships between HVPG and the complications or status of cirrhosis. METHODS:
      The HVPG, gastroesophageal varices, Child-Pugh score, Model for End-Stage Liver
      Disease (MELD) score, presence of ascites, recent bleeding history and the status
      of cirrhosis were assessed in a cohort of 172 patients (156 males, 16 females)
      with liver cirrhosis. RESULTS: The HVPG was 15.6+/-5.1 (mean+/-SD) mmHg (4-33
      mmHg) and was significantly higher in patients in the decompensated stage than in
      those in the compensated stage (16.6+/-4.3 vs. 10.8+/-6.1 mmHg, respectively;
      P<0.01). HVPG was higher in bleeders than in nonbleeders (16.9+/-4.5 vs. 12.8+/
      5.3 mmHg, respectively; P<0.01), and in patients with ascites than in those
      without ascites (16.4+/-4.1 vs. 14.5+/-6.2 mmHg, respectively; P<0.05). HVPG was
      significantly lower in the presence of gastric varices than in their absence
      (14.0+/-3.4 vs. 16.0+/-5.3 mmHg, respectively; P<0.05); however, no significant
      correlation was detected between HVPG and the grade of esophageal varices
      (P>0.05). HVPG was significantly higher in Child's B cirrhosis (n=87, 15.6+/-4.7
      mmHg) and Child's C cirrhosis (n=36, 18.4+/-4.7 mmHg) than in Child's A cirrhosis
      (n=49, 13.7+/-5.1 mmHg; P<0.01). HVPG also was strongly correlated with the MELD
      score (P<0.01). The time required to measure the HVPG was 11.2+/-6.4 min, and
      only three cases of minor complication occurred during the procedure.
      CONCLUSIONS: HVPG was correlated with the severity of liver cirrhosis, presence
      of ascites, and risk of variceal bleeding in patients with liver cirrhosis.

PMID- 18617764
TI  - [Incidence and risk factors of acute renal failure after transcatheter arterial
      chemoembolization for hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) is a major
      modality in the treatment of unresectable hepatocellular carcinoma. Acute renal
      failure (ARF) may occur after TACE because of underlying liver cirrhosis and the
      presence of radiocontrast agent. However, the data available regarding this
      complication are variable and limited. The aim of this study was to determine the
      incidence and associated risk factors of ARF after TACE. METHODS: From January
      2001 to December 2004, a total of 632 procedures were performed in 377 patients.
      Of these, the cases with high creatinine levels (> or = 2 mg/dL) before TACE and
      with incomplete medical records were excluded, which resulted in 463 procedures
      in 319 patients (256 males and 63 females; age 58.7+/-9.9 years, mean+/-SD) being
      examined for this study. Various clinical and radiological data before and after
      the procedure were reviewed retrospectively. RESULTS: ARF occurred following 15
      (3.2%) of the 463 procedures within 7 days of TACE. Univariate analysis revealed
      that serum albumin levels (P=0.025), Model for End-Stage Liver Disease score
      (P=0.001), the distribution of Child-Pugh class (P=0.027), and the proportions of
      patients with ascites (P<0.001), using diuretics (P=0.010), and with a serum
      creatinine level > or = 1.5 mg/dL (P=0.023) differed significantly between
      patients with or without ARF after TACE. In multivariate analysis, the presence
      of ascites (P=0.005; odds ratio, 5.297) and serum creatinine level > or = 1.5
      mg/dL (P=0.007; odds ratio, 7.358) were independently associated with the
      development of ARF. CONCLUSIONS: The incidence of ARF after TACE was 3.2%, and
      the presence of ascites and an abnormal baseline serum creatinine level were the
      risk factors for ARF.

PMID- 18617765
TI  - [Clinical feature of Fitz-Hugh-Curtis syndrome: analysis of 25 cases].
AB  - BACKGROUND/AIMS: Fitz-Hugh-Curtis syndrome is defined as perihepatitis associated
      with pelvic inflammatory disease (PID). We retrospectively analyzed clinical and
      laboratory manifestations as well as the therapeutic response in patients with
      clinically diagnosed Fitz-Hugh-Curtis syndrome. METHODS: A cohort of 25 patients
      with PID and perihepatitis (as diagnosed by dynamic abdominal computed tomography
      (CT)) was enrolled. The prognosis, clinical manifestations, and physical
      examination, laboratory, and CT findings were analyzed. RESULTS: The mean (+/-SD)
      age of the patients was 32(+/-8) years, and all of them were sexually active,
      premenopausal women, and presented with abdominal pain. Of these, 52% complained
      of vaginal discharge. On physical examination, right upper-quadrant tenderness
      was the most common finding (84%), with lower-abdominal tenderness being present
      in 20% of patients. On laboratory examination, erythrocyte sedimentation rate and
      C-reactive protein were increased in 76% and 92% of the patients, respectively.
      The white blood cell count was increased in 60% of them. Most patients had a
      normal liver function test. Using a specimen of the cervical discharge, the
      polymerase chain reaction to test for Chlamydia trachomatis were positive in 87%
      (13/15) of the patients, and Chlamydia antigen was found in 75% (9/12) of them.
      Dynamic abdominal CT revealed subcapsular enhancement of the liver in the
      arterial phase. All of the patients improved with antibiotic therapy.
      CONCLUSIONS: Symptoms and physical findings suggestive of PID are not present in
      many patients with Fitz-Hugh-Curtis syndrome. When a premenopausal woman
      complains of upper abdominal pain and shows CT findings compatible with
      perihepatitis, examination of cervical discharge would be recommended to assess
      the possibility of Fitz-Hugh-Curtis syndrome.

PMID- 18617766
TI  - [Expression of vascular endothelial growth factor (VEGF) family members and
      prognosis after hepatic resection in HBV-related hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Human hepatocellular carcinoma (HCC) is a hypervascular tumor,
      and vascular endothelial growth factor (VEGF) plays a key role in the regulation
      of tumor-associated angiogenesis. In this study, we analyzed the significance of
      the expression of VEGF family members on the prognosis and clinicopathologic
      progress of HCC. METHODS: Surgically resected specimens of HCC and noncancerous
      liver tissue were obtained from 323 patients with HCC, and VEGF mRNA was examined
      by quantitative reverse transcriptase-polymerase chain reactions (RT-PCRs).
      Patients who were seropositive for hepatitis B surface antigen were selected for
      the analysis (n=208). The VEGF(tumor)/GAPDH (glyceraldehyde-3-phosphate
      dehydrogenase)(tumor)/VEGF(nontumor)/GAPDH(nontumor) ratio was calculated using a
      quantitative RT-PCR assay, and the relationships between the expressions of VEGF
      family members and clinicopathologic parameters were analyzed to evaluate their
      significance in the prognosis of HCC. RESULTS: The disease-free survival was
      significantly worse in the high-VEGF-A group than in the low-VEGF-A group
      (P=0.035), whereas VEGF-A expression was not significantly related to overall
      survival (P=0.172). The factors significantly related to poor prognosis in
      univariate analysis were tumor size, portal vein invasion, microvascular thrombi,
      intrahepatic metastasis, tumor capsule invasion, liver capsule invasion,
      preoperative serum albumin level, and VEGF-A ratio. Multivariate analysis showed
      that a poor prognosis in HCC patients was significantly related to portal vein
      invasion (hazard ratio=3.381, P<0.001), intrahepatic metastasis (hazard
      ratio=2.379, P<0.001), tumor size (hazard ratio=1.834, P=0.003), and preoperative
      serum albumin level (hazard ratio=2.050, P=0.006). CONCLUSIONS: Our study showed
      that the expression of VEGF-A is positively correlated with the recurrence rate
      of HCC after curative resection. Therefore, a high expression of VEGF-A might be
      predictive of HCC recurrence after curative resection.

PMID- 18617767
TI  - [Hepatitis B core antigen expression pattern predicts response to lamivudine
      therapy in patients with chronic hepatitis B].
AB  - BACKGROUNDS/AIMS: Negative hepatitis B core antigen (HBcAg) staining in
      hepatocytes is indicative of viral replication by an active immune response.
      HBcAg is expressed mainly in the cytoplasm in patients with active hepatitis and
      hepatocyte regeneration, and mainly in the nuclei of hepatocytes in patients with
      minimal liver injury in the absence of hepatocyte regeneration. The aim of this
      study was to elucidate whether the existence and expression pattern of HBcAg
      predicts the response to antiviral treatment. METHODS: The study involved 58
      patients with biopsy-proven chronic hepatitis B who were treated with lamivudine.
      Hepatitis B e antigen (HBeAg), antibody to HBeAg, hepatitis B virus DNA, and
      alanine aminotransferase in serum were recorded every 3 months. The inflammation
      grade and the fibrosis stage of chronic hepatitis were scored from 0 to 4
      according to lobular inflammation, portal inflammation, periportal inflammation,
      and fibrosis. RESULTS: The 58 patients included 49(84%) HBcAg-positive patients,
      with HBcAg staining confined to the cytoplasm in 15(31%) and in both cytoplasm
      and nuclei in 34(69%). The grade of lobular inflammation and the total histology
      score were significantly higher in patients with cytoplasmic expression of HBcAg
      than in HBcAg-negative patients (lobular inflammation: 2.9 vs 2.1, P=0.02; total
      histology score: 12.2 vs 10.3, P=0.04). The virologic responses at 3, 6, 9, and
      12 months differed significantly between the cytoplasmic and mixed expression
      groups (P<0.01). CONCLUSIONS: The expression pattern of HBcAg (including its
      possible absence) before initial therapy appears to predict the response to
      antiviral treatment.

PMID- 18617768
TI  - [Four cases of toxic liver injury associated with Dictamnus dasycarpus].
AB  - We report four cases of toxic hepatitis that occurred after taking a decoction
      made by boiling down the root of Dictamnus dasycarpus. The four patients had a
      median age of 60 years, common symptoms of jaundice and general weakness, and
      stated that they had not consumed alcohol for at least 5 years. The markers of
      hepatitis A, B, and C were all negative in the patients. Abdominal
      ultrasonography revealed common bile ducts with normal diameters. Two of the
      cases were a mother and daughter, and the other two were sporadic. All of them
      had consumed a decoction made by boiling down the root of Dictamnus dasycarpus
      five or six times daily until several days before admission. Dictamnus dasycarpus
      induced liver injury presenting with a benign course lasting less than 1 month
      after cessation of the causative agent. We suggest that this natural product can
      cause acute hepatitis in rural areas.

PMID- 18617769
TI  - [Hepatitis B virus reactivation during chlorambucil and prednisolone treatment in
      an HBsAg-negative and anti-HBs-positive patient with B-cell chronic lymphocytic
      leukemia].
AB  - It is generally accepted that seroconversion of hepatitis B virus (HBV) surface
      antigen (HBsAg) to an antibody to HBsAg (anti-HBs) indicates clearance of HBV.
      Here we report a case of severe hepatitis that manifested during chemotherapy in
      a female patient with chronic lymphocytic leukemia (CLL) who had been initially
      seronegative for HBsAg and seropositive for anti-HBs. The patient received
      chlorambucil and prednisolone for the treatment of CLL. After 6 months the serum
      levels of aminotransferases were increased, and HBsAg and HBV DNA were present in
      serum. Lamivudine was administered immediately after confirming the HBV
      reactivation, which considerably improved jaundice and aminotransferase levels
      after 3 weeks. The patient was able to resume the chemotherapy whilst continuing
      lamivudine treatment. This case report highlights the need for physicians to be
      aware of the potential risk of HBV reactivation even in an HBsAg-negative person
      but with detectable anti-HBc and/or anti-HBs, underscoring the need for future
      studies that explore the role of antiviral prophylaxis in this setting.

PMID- 18617770
TI  - An adult case of glycogen storage disease type IIIa.
AB  - Glycogen storage disease type III (GSD III) is a very rare disorder caused by a
      deficiency in the activities of glycogen debranching enzymes (amylo-1-6
      glucosidase and 4-alpha-glucanotransferase). GSD III is characterized by the
      accumulation of abnormal glycogen in the liver and skeletal muscle. The primary
      clinical manifestations are hepatomegaly, fasting hypoglycemia, and
      hyperlipidemia in infants. We report a rare case of GSD III in an adult. A 52
      year-old woman presented to our clinic due to dyspnea on exertion, severe general
      weakness, and hepatomegaly. Hypertrophic cardiomyopathy was diagnosed based on
      echocardiogram findings. The microscopic findings of liver and skeletal muscle
      biopsies were consistent with the diagnosis of GSD. DNA analysis prompted by
      clinical and pathologic findings led to a definitive diagnosis of GSD IIIa. Diet
      therapy with cornstarch was started, and the patient was followed closely. This
      represents the first reported case of GSD IIIa diagnosed in an adult in Korea.

PMID- 18617771
TI  - [Focal nodular hyperplasia-like nodule in liver cirrhosis].

PMID- 18617772
TI  - [Radiologic findings of dysplastic nodule].

PMID- 18617774
TI  - Pancreatic cancer: a plea for good and comprehensive morphological studies.
AB  - Despite considerable progress, PDA carries a dismal prognosis. Recent advances in
      clinical and basic science have revealed new insights into pancreatic
      carcinogenesis. Compelling histopathological and molecular evidence support the
      evolution of PDA through a series of noninvasive duct lesions named PanINs.
      Progression of PanIN lesions is associated with genetic and biochemical
      aberrations correlating with advancing cellular atypia from early stages to
      invasive cancer. Several studies with pancreatic resection specimens revealed a
      sequence of genetic changes including activating K-ras mutations, overexpression
      of the growth factor receptor HER-2/neu, and the inactivation of the tumor
      suppressor genes INK4A/ARF, TP53, Smad4/DPC4, and BRCA2. The availability of
      mouse models mimicking human pancreatic cancer allows functional studies which
      will evaluate relevance for the human disease. Moreover, the precise knowledge of
      critical events in pancreatic carcinogenesis opens new horizons in designing new
      diagnostic and therapeutic strategies against this fatal disease.

PMID- 18617775
TI  - Gastro-oesophageal reflux disease and irritable bowel syndrome: a significant
      association in an Iranian population.
AB  - BACKGROUND: Gastro-oesophageal reflux disease and irritable bowel syndrome are
      common diseases, which may be related. AIM: To assess the association between
      gastro-oesophageal reflux disease and irritable bowel syndrome in a country with
      high prevalence of Helicobacter pylori. METHODS: This study was designed as cross
      sectional and population-based in Tehran province, Iran. The participants were
      interviewed by using a valid and reliable questionnaire. Gastro-oesophageal
      reflux disease was defined by weekly or more frequent heartburn and/or acid
      regurgitation. Irritable bowel syndrome was diagnosed according to the Rome III.
      The association between these two disorders was calculated using a statistical
      model that allows the odds ratio (OR) to be measured. RESULTS: A total of 6526
      individuals were selected randomly, the response rate was 87.8%. Among the
      respondents, 178 (3.1%) participants reported both the diseases. The OR of having
      gastro-oesophageal reflux disease and irritable bowel syndrome together was
      estimated to be 16.55 (95% confidence interval: 12.85-21.33) indicating
      significant association between the two diseases. Thirty-four percent of patients
      with gastro-oesophageal reflux disease and 61.5% with irritable bowel syndrome
      suffered from both diseases. Sex did not have a significant effect on the OR of
      coexistence. Older participants were statistically more prone to the coexistence
      of two diseases. CONCLUSION: The association between gastro-oesophageal reflux
      disease and irritable bowel syndrome was significantly higher in our community
      compared with others. Their association occurs predominantly in older
      participants. Further studies for understanding of the pathophysiological
      mechanisms behind these two diseases are required.

PMID- 18617776
TI  - The SPINK1 N34S variant is associated with acute pancreatitis.
AB  - OBJECTIVE: Acute pancreatitis (AP) is a disease whose pathogenesis remains
      largely obscure. Genetic research has focussed attention upon the role of the
      pancreatic protease/protease inhibitor system. The aim of this study was to
      investigate the prevalence of genetic variants of the trypsin inhibitor, SPINK1,
      in acute pancreatitis. METHODS: We genotyped 468 patients with AP and 1117
      healthy controls for SPINK1 alterations by single-strand conformation
      polymorphism analysis and by melting curve analysis using fluorescence resonance
      energy transfer probes. RESULTS: The c.101A>G (p.N34S) variant was detected in
      24/936 alleles of patients and in 18/2234 alleles of healthy controls (odds
      ratio=3.240; 95% confidence interval: 1.766-5.945; P<0.001). In the UK patients,
      the mean age of patients with N34S was 11.9 years younger compared with N34S
      negative patients (P=0.023), but this was not apparent in the German patients.
      Allele frequencies for the c.163C>T (p.P55S) variant did not differ between
      patients and controls. CONCLUSION: The SPINK1 N34S variant is associated with
      acute pancreatitis. This supports the importance of premature protease activation
      in the pathogenesis of AP and suggests that mutated SPINK1 may predispose certain
      individuals to develop this disease.

PMID- 18617777
TI  - Expression of COX-2 is associated with accumulation of p53 in pancreatic cancer:
      analysis of COX-2 and p53 expression in premalignant and malignant ductal
      pancreatic lesions.
AB  - OBJECTIVES: Cyclooxygenase-2 (COX-2) and tumor suppressor p53 are molecules that
      are linked to the oncogenesis of pancreatic cancer. COX-2 represents a key
      modulatory molecule in inflammation and carcinogenesis, and is known to be
      implicated in the positive regulation of growth and tumorigenesis. Abnormal
      expression of p53 is common in many human neoplasms including pancreatic cancer.
      Recent studies demonstrated functional interactions between p53 and COX-2. The
      p53-dependent upregulation of COX-2 was proposed to be another mechanism by which
      p53 could abate its own growth-inhibitory and apoptotic effects. METHODS: In this
      study, we immunohistochemically analyzed the expression of COX-2 and p53 in 95
      pancreatic resection specimens [adenocarcinomas, 95 lesions; pancreatic
      intraepithelial neoplasias (PanINs), 155; normal ducts, 70]. RESULTS: The
      expression of COX-2 increased progressively with the grade of ductal lesions
      (P<0.00001). A statistically significant difference of COX-2 expression between
      normal ducts and low-grade PanINs was revealed (P=0.0042). COX-2 overexpression
      was demonstrated in 82 PanINs (52.9%), and in 76 adenocarcinomas (80%). No
      significant correlation between the grade of adenocarcinoma and COX-2 expression
      was revealed (P=0.2). The expression of p53 again increased progressively with
      the grade of lesions (P<0.00001) with a significant increase in high-grade
      PanINs. A correlation between COX-2 and p53 expression levels in carcinomas was
      revealed (P=0.0002), and an accumulation of p53 was associated with COX-2
      overexpression in premalignant and malignant ductal lesions. CONCLUSION: These
      findings confirmed the generally accepted pancreatic cancer progression model,
      and supported the concept of the interactive role of COX-2 and p53 in pancreatic
      cancer carcinogenesis, which offers opportunities for targeted therapy and
      chemoprevention of pancreatic cancer using COX-2 inhibitors.

PMID- 18617778
TI  - High prevalence of morphometric vertebral deformities in patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Earlier studies have documented that the prevalence of decreased bone
      mineral density (BMD) is elevated in patients with inflammatory bowel disease.
      The objective of this study was to investigate the prevalence of vertebral
      deformities in inflammatory bowel disease patients and their relation with BMD
      and bone turnover. METHODS: One hundred and nine patients with Crohn's disease
      (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied.
      BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single
      energy densitometry of the spine for assessment of vertebral deformities was
      performed. Serum markers of bone resorption (carboxy-terminal cross-linked
      telopeptide of type I collagen) and formation (procollagen type I amino-terminal
      propeptide) were measured, and determinants of prevalent vertebral deformities
      were assessed using logistic regression analysis. RESULTS: Vertebral deformities
      were found in 25% of both CD and UC patients. Comparing patients with and without
      vertebral deformities, no significant difference was found between Z-scores and T
      scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of
      type I collagen and serum procollagen type I amino-terminal propeptide. Using
      logistic regression analysis the only determinant of any morphometric vertebral
      deformity was sex. The presence of multiple vertebral deformities was associated
      with older age and glucocorticoid use. CONCLUSION: The prevalence of morphometric
      vertebral deformities is high in CD and UC. Male sex, but neither disease
      activity, bone turnover markers, clinical risk factors, nor BMD predicted their
      presence. The determinants for having more than one vertebral deformity were age
      and glucocorticoid use. This implies that in addition to screening for low BMD,
      morphometric assessment of vertebral deformities is warranted in CD and UC.

PMID- 18617779
TI  - The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic
      disease behavior in patients with Crohn's disease.
AB  - OBJECTIVES: CX3CR1, the receptor of CX3CL1/fractalkine, is involved in regulation
      of inflammatory response and the CX3CR1-I249-M280 naturally occurring mutants are
      associated with altered binding to the ligand. Our aim was to evaluate the
      frequency of CX3CR1 V249I and T280M polymorphisms and NOD2/CARD15 mutations in
      Crohn's disease patients and to search for a relationship with phenotype.
      METHODS: Clinical data were retrospectively collected. V249I and T280M
      polymorphisms of CX3CR1 gene and NOD2/CARD15 mutations (R702W, G908R, 3020InsC)
      were identified. RESULTS: Two hundred and thirty-nine patients (140 females,
      39.7+/-14.1 years) were included. About 37.4% were heterozygous and 8.8% were
      homozygous for the V249I CX3CR1 polymorphism, 18.1% were heterozygous and 1.3%
      homozygous for the T280M CX3CR1 polymorphism and 35.9% had at least one of the
      three mutations of NOD2/CARD15. The T280M CX3CR1 polymorphism was not associated
      with any phenotype. In univariate analysis, stenosis was significantly associated
      with both V249I CX3CR1 polymorphism and 3020InsC NOD2/CARD15 mutations. In smoker
      patients carrying the CX3CR1 allele I249, there was a significant increase in the
      frequency of fibrostenosing disease [P=0.005, odds ratio (OR): 3.25] whereas this
      relationship disappeared in the group of nonsmokers (P=0.72). In multivariate
      analysis, 3020InsC NOD2/CARD15 mutations and the V249I CX3CR1 polymorphism were
      independent risk factors for intestinal stenosis (P=0.046, OR: 1.8 and P=0.044,
      OR: 2.4, respectively). CONCLUSION: In Crohn's disease, V249I CX3CR1 polymorphism
      is associated with intestinal strictures, particularly in smokers. This
      association is independent of CARD15 mutations.

PMID- 18617780
TI  - Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal
      carcinoma.
AB  - AIM: To propose a quantitative method to detect heparanase-2 (HPA2) and syndecan
      1 (Syn-1) using immunohistochemistry in colorectal (colon and rectal) carcinomas
      compared with nonneoplastic tissues and evaluate the possible role of these
      molecules in tumor development and extracellular remodeling. METHODS: Cytoplasmic
      staining of HPA2 and Syn-1 was obtained by standard immunohistochemical reactions
      in 50 colorectal carcinoma and 20 nonneoplastic large bowels tissues. An image
      system was used to quantify the immunoexpression by digital computer-assisted
      method (Matos et al. 2006). The cutoff point for the immunohistochemistry
      variable was defined by sensibility and specificity curves. Statistical analysis
      was performed using SPSS version 13.0. RESULTS: HPA2 was over-expressed in
      colorectal cancer (131.1+/-24.9 o.u./microm) when compared with nonneoplastic
      tissues (27.9+/-12.2 o.u./microm) (P<0.0001). However, an opposite correlation
      was observed between Syn-1 and tumor presence, where colorectal tissues expressed
      lower Syn-1 proteoglycan compared with nonneoplastic tissues, respectively
      (39.2+/-17.8 o.u./microm) and (102.2+/-25.2 o.u./microm) (P<0.0001). CONCLUSION:
      A methodology with high sensitivity and specificity is proposed with a cutoff
      value for HPA2 and Syn-1 in the immunohistochemistry assay to define the presence
      of tumor. It was demonstrated for the first time in the literature that HPA2 is
      over-expressed in colorectal carcinoma tissues compared with nonneoplastic
      tissues. HPA2 over-expression could be possibly related to Syn-1 shedding despite
      the fact that HPA2 does not present enzymatic activity as HPA1.

PMID- 18617781
TI  - Predictive factors of years of potential life lost by colorectal cancer.
AB  - OBJECTIVE: To evaluate the impact of colorectal cancer (CRC) by estimating the
      years of potential life lost (YPLL) by this neoplasm in a cohort of patients, as
      well as to define the predictive factors of YPLL. METHODS: A descriptive cross
      sectional study of 980 consecutive patients diagnosed and treated because of CRC
      in our institution between 1985 and 2002 was carried out. Demographic, clinical,
      pathological, surgical, hospital stay, complications, and mortality variables
      were recorded. The primary endpoint of this study was to calculate individual
      YPLL. Univariate analysis was performed to compare each independent variable with
      the variable YPLL. All clinically relevant variables significantly associated
      with YPLL were included in an ordinal regression model to identify independent
      factors prognostic of YPLL. RESULTS: The final study sample was 794 patients, 413
      (52%) men and 381 (48%) women, mean age 65.3 years [confidence interval (CI) 95%:
      64.4-66.2 years; SD: 12.8]. The mean global YPLL for the 351 patients who died of
      CRC was 15.2 years (SD: 10.7; CI 95%: 14.1-16.3). Lower age [odds ratio
      (OR)=0.98; CI 95%: 0.97-0.98], male sex (OR=1.19; CI 95%: 1.00-1.43), lower
      tumor, nodes, metastasis (TNM) stage (OR=0.29; CI 95%: 0.24-0.35), and rectum
      localization of the tumor (OR=1.37; CI 95%: 1.14-1.64) were independent
      prognostic factors for YPLL. CONCLUSION: In our community, the mean number of
      YPLL by CRC exceeds 15 years. Lower age, male sex, higher TNM stage, and rectum
      localization are negative predictors of YPLL.

PMID- 18617782
TI  - Selection of an entecavir-resistant mutant despite prolonged hepatitis B virus
      DNA suppression, in a chronic hepatitis B patient with preexistent lamivudine
      resistance: successful rescue therapy with tenofovir.
AB  - BACKGROUND AND OBJECTIVE: Entecavir has potent activity against hepatitis B
      virus. Drug resistance has not been reported in nucleoside-naive patients and is
      low in lamivudine-refractory patients. METHODS AND RESULTS: A 43-year-old man was
      treated with lamivudine for hepatitis B e antigen-positive chronic hepatitis B. A
      viral breakthrough owing to a drug-resistant mutant was observed and entecavir 1
      mg daily was added. After the viral load had been near the lower detection range
      of the PCR assay for 30 weeks, lamivudine was discontinued. The serum hepatitis B
      virus DNA remained low until a second viral breakthrough was observed after 45
      weeks of entecavir monotherapy. Treatment was switched from entecavir to
      tenofovir disoproxil 245 mg daily, which resulted in a decline below 1000
      copies/ml. Sequence analysis revealed the presence of rtL180M and rtM204V
      lamivudine-resistant-associated mutations at the start of entecavir treatment.
      During entecavir treatment, the rtS202G mutation was selected. Retrospective
      analysis revealed that during lamivudine treatment three other mutations had been
      selected as well, namely rtE1D, rtV207L, and rtI220L. CONCLUSION: We describe the
      first case of entecavir resistance in a lamivudine-resistant patient with good
      initial suppression of viral replication for 70 weeks. On the basis of the data
      from cross-resistance and sensitivity testing in vitro and treatment outcomes,
      tenofovir proves to be a good treatment option for entecavir-resistant patients.

PMID- 18617783
TI  - Antiviral therapy for recurrent hepatitis C after liver transplantation:
      sustained virologic response is related to genotype 2/3 and response at week 12.
AB  - OBJECTIVES: Recurrent hepatitis C virus (HCV) infection after liver
      transplantation (LT) is a major cause of transplant failure in HCV-positive
      patients. We retrospectively assessed the efficacy and safety of antiviral
      therapy and determined the factors influencing sustained virologic response (SVR)
      in LT recipients. METHODS: Between 1998 and 2007, we treated 36 LT recipients for
      hepatitis C cirrhosis and subsequent HCV recurrence (27 genotype 1 and 9
      genotypes 2/3) with pegylated interferon alpha-2a (180 microg/week), pegylated
      interferon alpha-2b (1.5 microg/kg per week), or standard interferon alpha-2b (3
      MIU 3X/week) plus ribavirin (600-1200 mg/day) for 48 weeks. RESULTS: SVR was
      achieved in seven of 27 (26%) of genotype 1 patients versus nine of nine (100%)
      genotype 2/3 patients (P=0.0001). Early virologic response at week 12 was
      associated with permanent viral clearance. Side effects included cytopenia and
      acute hearing loss, but rate of therapy withdrawal and dose reduction was low.
      CONCLUSION: Combination therapy in patients with HCV reinfection after LT yields
      an excellent SVR rate in genotype 2/3 patients, but remains unsatisfactory in
      genotype 1 patients. Virologic response at week 12 (early virologic response) can
      determine whether therapy should be continued or not.

PMID- 18617784
TI  - Autochthonous hepatitis E in Southwest England: natural history, complications
      and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors,
      the elderly and patients with chronic liver disease.
AB  - AIMS: To report the natural history of autochthonous hepatitis E and hepatitis E
      virus (HEV) IgG seroprevalence in Southwest England. METHODS: Patients with
      unexplained hepatitis were tested for hepatitis E and cases followed until
      recovery or death. Five hundred blood donors, 336 individuals over the age of 60
      years and 126 patients with chronic liver disease were tested for HEV IgG.
      RESULTS: Forty cases of autochthonous hepatitis E (genotype 3) were identified.
      Hepatitis E was anicteric in 25% of cases and usually caused a self-limiting
      hepatitis predominantly in elderly Caucasian males. Six of 40 had a significant
      complication and three patients died, two of who had previously undiagnosed
      cirrhosis. Hepatitis E shows a seasonal variation with peaks in the spring and
      summer and no cases in November and December. HEV IgG prevalence increases with
      age, is more common in men and is 16% in blood donors, 13% in patients with
      chronic liver disease and 25% in individuals over 60 years. CONCLUSION:
      Autochthonous hepatitis E is more common than previously recognized, and should
      be considered in the differential diagnosis in patients with hepatitis, whatever
      their age or travel history. It carries a significant morbidity and when seen in
      the context of chronic liver disease carries an adverse prognosis.

PMID- 18617785
TI  - Composite marginal zone B cell lymphoma and enteropathy-type T cell lymphoma of
      the stomach: a case report.
AB  - We describe a 64-year-old patient with gastric synchronous extranodal marginal
      zone B cell lymphoma of mucosa-associated lymphoid tissue and enteropathy-type T
      cell lymphoma. The simultaneous occurrence of mucosa-associated lymphoid tissue
      lymphoma and enteropathy-type T cell lymphoma is exceptional and has never been
      reported. We discuss the possible pathogenetic relationship between the two
      neoplasms.

PMID- 18617786
TI  - Minocycline hepatitis.
AB  - Minocycline is an effective antibiotic widely used in the treatment of acne
      vulgaris. We report a previously well 20-year-old woman who developed liver
      dysfunction with jaundice and malaise following a 1 year course of minocycline
      for acne vulgaris. Serum antinuclear antibody was strongly positive (1 : 2560)
      and liver transaminases were grossly deranged. All other causes of liver disease
      were excluded. Both the clinical symptoms and laboratory abnormalities resolved
      spontaneously on stopping the drug. We review the three different types of
      hepatotoxicity associated with minocycline and draw evidence to support the
      diagnosis of minocycline-induced autoimmune hepatitis. This case supports the
      call to monitor patients on minocycline therapy for autoimmune disease of the
      liver and highlights the need for a multicentre prospective trial of the risks
      and benefits of long-term minocycline therapy.

PMID- 18617787
TI  - Hepatitis E autochthonous infection in chronic liver disease.
AB  - Hepatitis E virus is endemic in many parts of the developing world and causes a
      self-limiting hepatitis in young adults, except in pregnant women and patients
      with chronic liver disease, where the mortality is high. Locally acquired
      hepatitis E is increasingly recognized in the developed world. It is caused by
      hepatitis E virus genotype 3, affects the middle-aged and the elderly, and may be
      a zoonotic infection from pigs. We present a case of locally acquired hepatitis E
      infection in a patient with previously undiagnosed cirrhosis, which resulted in
      subacute liver failure and death. We describe our attempt to trace this infection
      to a free-range pig farm adjacent to the patient's place of employment. Hepatitis
      E infection should be considered in the differential diagnosis in patients with
      decompensated chronic liver disease whatever their age or travel history. When
      found, the prognosis may be poor.

PMID- 18617788
TI  - Spontaneous regression of hepatocellular carcinoma is possible and might have
      implications for future therapies.
AB  - Hepatocellular carcinoma is a potentially challenging cancer with very high
      mortality. Medical therapies are generally ineffective in achieving complete
      remission, especially for aggressive types or for advanced stage cancers.
      Spontaneous regression of these tumors is a rare and fascinating phenomenon. We
      describe such a patient with spontaneous regression of a large multi-focal
      hepatocellular carcinoma, and present a comprehensive review of the reported
      cases with a special emphasis on potential regression mechanisms.

PMID- 18617789
TI  - Pravastatin-induced colitis.
AB  - We report an unusual case of pravastatin-induced colitis in an 80-year old lady.
      Onset of symptoms was noted within 48 h of starting the medication. Colonoscopy
      revealed diffuse ulceration throughout the colon with relative sparing of the
      rectum, with the biopsies showing ulceration and inflammation. The patient
      received a short course of steroid therapy and 5 months after stopping
      pravastatin, there was complete macroscopic and microscopic resolution of the
      colonic lesions. Drug interaction of pravastatin with amitryptiline could have
      resulted in this uncommon complication.

PMID- 18617790
TI  - Neurofuzzy systems for the prediction of outcome in acute lower gastrointestinal
      hemorrhage.

PMID- 18617792
TI  - RSO interview with Patrick Muldoon.

PMID- 18617793
TI  - Characterization of 14C in Swedish light water reactors.
AB  - This paper presents the results of a 4-y investigation of 14C in different waste
      streams of both boiling water reactors (BWRs) and pressurized water reactors
      (PWRs). Due to the potential impact of 14C on human health, minimizing waste and
      releases from the nuclear power industry is of considerable interest. The
      experimental data and conclusions may be implemented to select appropriate waste
      management strategies and practices at reactor units and disposal facilities.
      Organic and inorganic 14C in spent ion exchange resins, process water systems,
      ejector off-gas and replaced steam generator tubes were analyzed using a recently
      developed extraction method. Separate analysis of the chemical species is of
      importance in order to model and predict the fate of 14C within process systems
      as well as in dose calculations for disposal facilities. By combining the results
      of this investigation with newly calculated production rates, mass balance
      assessments were made of the 14C originating from production in the coolant. Of
      the 14C formed in the coolant of BWRs, 0.6-0.8% was found to be accumulated in
      the ion exchange resins (core-specific production rate in the coolant of a 2,500
      MWth BWR calculated to be 580 GBq GW(e)(-1) y(-1)). The corresponding value for
      PWRs was 6-10% (production rate in a 2,775 MWth PWR calculated to be 350 GBq
      GW(e)(-1) y(-1)). The 14C released with liquid discharges was found to be
      insignificant, constituting less than 0.5% of the production in the coolant. The
      stack releases, routinely measured at the power plants, were found to correspond
      to 60-155% of the calculated coolant production, with large variations between
      the BWR units.

PMID- 18617794
TI  - Proposed standards for acute exposure to low enrichment uranium for compliance
      with 10 CFR 70.61.
AB  - Title 10, Code of Federal Regulations Part 70, puts forth requirements for
      licensure of special nuclear material including specific risk criteria for acute
      intakes based on biological effects. Standards for acute oral and inhalation
      intakes of soluble low enrichment are proposed for the three levels of biological
      effects given in the regulations. These levels were developed largely from
      available human data and have a large measure of conservatism. The proposed
      threshold for life endangerment was 500 mg for acute inhalation intakes and 2,500
      mg for acute ingestion intakes. Acute intakes of 1,400 mg for ingestion and 100
      mg for inhalation are proposed as thresholds for irreversible or serious long
      lasting health effects. For minor transient health effects, the proposed levels
      are 410 and 30 mg, respectively, for acute ingestion and inhalation intakes. For
      acute intakes below these levels, no demonstrable toxicological effects are
      anticipated.

PMID- 18617795
TI  - Statistical criteria to set alarm levels for continuous measurements of ground
      contamination.
AB  - In the course of the decommissioning of the ASTRA research reactor at the site of
      the Austrian Research Centers at Seibersdorf, the operator and licensee, Nuclear
      Engineering Seibersdorf, conducted an extensive site survey and characterization
      to demonstrate compliance with regulatory site release criteria. This survey
      included radiological characterization of approximately 400,000 m(2) of open land
      on the Austrian Research Centers premises. Part of this survey was conducted
      using a mobile large-area gas proportional counter, continuously recording
      measurements while it was moved at a speed of 0.5 ms(-1). In order to set
      reasonable investigation levels, two alarm levels based on statistical
      considerations were developed. This paper describes the derivation of these alarm
      levels and the operational experience gained by detector deployment in the field.

PMID- 18617796
TI  - Inspection of lead aprons: a practical rejection model.
AB  - As a sequel to the article by Ken Lambert and Tara McKeon, we propose a model by
      which defects in lead aprons may easily be evaluated on a routine basis. The
      model is applicable to lead aprons of various lead equivalent thicknesses. As
      recommended rejection criteria, we have used the concept of additional dose that
      an individual might receive due to defects in the lead (Pb) apron. The model has
      been implemented as an annual quality check in a large medical facility. In this
      article we consider only dose-related rejection criteria, since financial aspects
      related to ALARA have already been addressed in the abovementioned article.

PMID- 18617797
TI  - Web-based training course for evaluating radiological dose assessment in NRC's
      license termination process.
AB  - As part of the requirement for terminating the licenses of nuclear power plants
      or other nuclear facilities, license termination plans or decommissioning plans
      are submitted by the licensee to the U.S. Nuclear Regulatory Commission (NRC) for
      review and approval. Decommissioning plans generally refer to the decommissioning
      of nonreactor facilities, while license termination plans specifically refer to
      the decommissioning of nuclear reactor facilities. To provide a uniform and
      consistent review of dose modeling aspects of these plans and to address NRC-wide
      knowledge management issues, the NRC, in 2006, commissioned Argonne National
      Laboratory to develop a Web-based training course on reviewing radiological dose
      assessments for license termination. The course, which had first been developed
      in 2005 to target specific aspects of the review processes for license
      termination plans and decommissioning plans, evolved from a live classroom course
      into a Web-based training course in 2006. The objective of the Web-based training
      course is to train NRC staff members (who have various relevant job functions and
      are located at headquarters, regional offices, and site locations) to conduct an
      effective review of dose modeling in accordance with the latest NRC guidance,
      including NUREG-1757, Volumes 1 and 2. The exact size of the staff population who
      will receive the training has not yet been accurately determined but will depend
      on various factors such as the decommissioning activities at the NRC. This Web
      based training course is designed to give NRC staff members modern, flexible
      access to training. To this end, the course is divided into 16 modules: 9 core
      modules that deal with basic topics, and 7 advanced modules that deal with
      complex issues or job-specific topics. The core and advanced modules are tailored
      to various NRC staff members with different job functions. The Web-based system
      uses the commercially available software Articulate, which incorporates audio,
      video, and animation in slide presentations and has glossary, document search,
      and Internet connectivity features. The training course has been implemented on
      an NRC system that allows staff members to register, select courses, track
      records, and self-administer quizzes.

PMID- 18617798
TI  - Impact of the revision of 10CFR835 with regard to neutron field surveys.
AB  - The compliance requirements for Department of Energy facilities are codified in
      Title 10 Code of Federal Regulations Part 835. The regulation was recently
      revised to adopt the 1990 Recommendations of the International Commission on
      Radiological Protection (ICRP). Although the impacts of this change include areas
      other than neutron dosimetry, the intent of this text is to outline the new
      regulation's effect on neutron instrument calibrations and field surveys. A
      significant change as a result of the adoption of the ICRP 60 recommendations is
      the change in the quality factor applied to operational quantities including the
      quantity used for area monitoring and instrument calibrations, notably the
      ambient dose equivalent, H*(d). Since the definitions of the operational
      quantities were not changed, the absorbed dose values for these quantities remain
      consistent with previous recommendations so the only adjustment necessary is to
      account for the revised quality factors. For this work, commonly encountered
      neutron spectra were folded with energy dependent conversion coefficients,
      h*(10)(E), determined using the old and new quality factors to compute conversion
      coefficients for the various sources. Additionally, the effect on a single point
      calibration for the widely used "Rem ball" is discussed. In general, the change
      in conversion coefficients under the newer guidelines results in a 5 to 15%
      increase in H*(10), which will require modifications to instrument calibrations.

PMID- 18617799
TI  - Population attributable fraction for lung cancer due to residential radon in
      Switzerland and Germany.
AB  - Studies on miners as well as epidemiological studies in the general population
      show an increased lung cancer risk after exposure to radon and its progeny. The
      European pooled analysis of indoor radon studies estimates an excess relative
      risk of 8% (16% after correction for measurement uncertainties) per 100 Bq m(-3)
      indoor radon concentration. Here, we determine the population attributable
      fraction (PAF) for lung cancer due to residential radon based on this risk
      estimate for Switzerland and Germany. Based on regionally stratified radon data,
      the PAF was calculated following the World Health Organization concept of global
      burden of disease, compared to a realistic baseline radon concentration equal to
      the outdoor concentration. Lifetable approaches were used taking smoking and sex
      into account. Measurement error corrections were applied to both risk estimates
      and the radon distribution. In Switzerland, the average indoor radon
      concentration is 78 Bq m(-3), resulting in a PAF of 8.3%. Therefore, 169 male
      lung cancer deaths and 62 deaths in women can be attributed to residential radon
      per year. For Germany, the average indoor radon concentration is 49 Bq m(-3),
      corresponding to a PAF of 5.0% (1,422 male and 474 female deaths annually). In
      both countries, a large regional variation in the PAF was observed due to
      regional differences in radon concentrations and population structure. Both
      calculations show a strong dependency on the risk model used. Risk models based
      on miner studies result in higher PAF estimates than risk models based on indoor
      radon studies due to different assumptions regarding exposures received more than
      35 years ago. The use of a non-zero baseline radon concentration also contributes
      to the lower PAF estimates reported here. Although the estimates of the
      population attributable fraction of residential radon presented here are lower
      than previously reported estimates, the risk is still one of the most widespread
      environmental hazards. Radon monitoring and radon reduction programs are
      therefore important issues for environmental public health management.

PMID- 18617800
TI  - Dose to the public from tritium released to the atmosphere from the Livermore
      site of Lawrence Livermore National Laboratory, 1953 through 2005.
AB  - Throughout 53 years of operations, an estimated 29,300 TBq of tritium were
      released to the atmosphere at the Livermore site of Lawrence Livermore National
      Laboratory (LLNL); about 75% of this was released as tritium gas primarily in two
      accidental releases. A tritium dose reconstruction was undertaken to chronicle
      both the annual doses to the public for each year of operations and the doses
      from seven accidental releases. Although LLNL has always reported releases and
      calculated doses in compliance with regulatory requirements, annual doses were
      not calculated prior to 1973, and the only dose reported from an accidental
      release was that in 1970. Annual doses (means and 95% confidence intervals) for
      1953 through 2005 to the most exposed members of the public were calculated using
      the same equilibrium dose model and assumptions. From 1973 through 2005,
      predicted tritium concentrations in air were compared with observed mean annual
      concentrations at one location, and predicted doses were compared with those
      reported by LLNL. A mean dose with 95% confidence interval was also calculated
      for each accidental release using an equation derived from extensive experience
      with a dynamic process-oriented model. Predicted air concentrations were
      overestimated, on average, by a factor of 1.6, 70% of the doses reported by LLNL
      in annual compliance documents fell within the predicted confidence intervals,
      and all predicted doses from routine and accidental releases were well below
      regulatory limits. The highest annual mean dose to an adult was 34 microSv in
      1957; the highest dose from an accidental release was 330 microSv in 1954.

PMID- 18617801
TI  - Tritium recapture behavior at a nuclear power reactor due to airborne releases.
AB  - This paper describes the initiatives taken by Cook Nuclear Plant to study the on
      site behavior of recaptured tritium released in its airborne effluents. Recapture
      is the process where a released radioactive effluent, in this case tritium, is
      brought back on-site through some mechanism. Precipitation, shifts in wind
      direction, or anthropogenic structures that restrict or alter effluent movement
      can all lead to recapture. The investigation was started after tritium was
      detected in the north storm drain outfall. Recent inadvertent tritium releases by
      several other nuclear power plants, many of which entered the groundwater, have
      led to increased surveillance and scrutiny by regulatory authorities and the
      general public. To determine the source of tritium in the outfall, an on-site
      surface water, well water, rainwater and air-conditioning condensate monitoring
      program was begun. Washout coefficients were also determined to compare with
      results reported by other nuclear power plants. Program monitoring revealed
      detectable tritium concentrations in several precipitation sample locations
      downwind of the two monitored containment building release vents. Tritium was
      found in higher concentrations in air-conditioning condensate, with a mean value
      of 528 Bq L(-1) (14,300 pCi L(-1)). The condensate, and to a lesser extent
      rainwater, were contributing to the tritium found in the north storm drain
      outfall. Maximum concentration values for each sample type were used to estimate
      the most conservative dose. A maximum dose of 1.1 x 10(-10) mSv (1.1 x 10(-8)
      mrem) total body was calculated to determine the health impact of the tritium
      detected.

PMID- 18617802
TI  - An experimental analysis of the contribution of 228Ra progeny to the gross alpha
      particle activity of water samples.
AB  - The contribution of 228Ra progeny to the gross alpha-particle activity of water
      samples by EPA Method 900.0 is investigated as a function of residue mass and
      geometry and time between sample collection and analysis. It is shown that these
      factors can cause the contribution of 228Ra progeny to gross alpha-particle
      activity to be up to 2.2 times the initial 228Ra activity for grab samples and up
      to 3.5 times the initial 228Ra activity for quarterly composite samples when
      samples are held for the maximum 6-mo holding time. Thus, under some conditions,
      228Ra, by itself, can cause a gross alpha-particle violation (>0.55 Bq L(-1)).
      Since 228Ra activity is already regulated, a gross alpha-particle activity
      violation that only exists because of the presence of 228Ra can be considered to
      be a false positive violation.

PMID- 18617803
TI  - Radiation dose to surgical staff from positron-emitter-based localization and
      radiosurgery of tumors.
AB  - Surgical tissue characterization based on radiotracer uptake has become much more
      common in recent years, particularly due to the advent of the sentinel lymph node
      biopsy technique. Radiolabeled pharmaceuticals are used with hand-held gamma
      sensitive probes, which are capable of localizing small tumors and lymph nodes
      that are first identified via scintigraphy. The radiation safety of such
      radioguided procedures, which typically employ 99mTc, has been well established.
      Now, with the emergence of 18F-fluorodeoxyglucose (18FDG) as a widely used tracer
      for PET imaging of cancer patients, there is increasing interest in the
      possibility of utilizing 18FDG for intraoperative tumor detection. First, though,
      the exposure to operating room personnel must be shown to be at a safe level. Due
      to the short half-life of 18F, the exposure rate will vary significantly with the
      start time post-injection as well as the duration of the procedure. The aim of
      this investigation is to determine empirically an exposure rate equation that can
      be integrated to estimate the exposure to a surgeon and assistants, from patients
      injected with 18FDG, over an arbitrarily chosen time interval. The study was
      conducted by measuring the radiation exposure rate from hospital in-patients
      receiving 18FDG-PET scans at various times from one to seven hours post
      injection; the empirical equation was determined from the plot of exposure rate
      vs. time for all patients. The resulting effective dose equivalent for the
      surgeon for typical values of injected activity, delay time and procedure
      duration was approximately 60 microSv.

PMID- 18617804
TI  - Correlation between external exposure and activity in patients undergoing 131I
      thyroid cancer therapy.
AB  - The uptake and clearance of 131I activity for inpatients undergoing cancer
      therapy were determined from routine external dose survey measurements. A bi
      exponential behavior was found, with the two time constants representing the
      iodine dynamics in the thyroid on one hand and in the rest of the body on the
      other. The external dose at 1 m from the patient was correlated to the activity
      in the thyroid remnant and inside the body, the averaged value being 52.8 +/-
      11.4 microSv GBq(-1) h(-1). The temporal evolution of activity in the body, the
      urinary system and the thyroid remnant area were determined taking into account
      the clearance from thyroid and whole body (effective retention constants averages
      0.23 +/- 0.14 d(-1) and 1.46 +/- 0.34 d(-1)) and the uptake in thyroid (3.15 +/-
      3.36%). Applications of this study in the public and environmental radiation
      protection areas are presented.

PMID- 18617805
TI  - Effect of mass, at a fixed height, on the counting efficiency of a BOMAB phantom
      in three types of whole body counter modeled by MCNP5.
AB  - Using demographic data, a series of BOMAB phantoms were developed to study the
      effect of size, at a fixed height, of a BOMAB phantom using Monte Carlo
      simulations in three different whole body counting systems: the HML's scanning
      detector whole body counter, a FastScan whole body counter, and a StandFast whole
      body counter. The latter has had two counting geometries simulated--one for the
      recommended position, and another simulating a constant detector-to-front-of
      phantom distance. The six phantom sizes corresponded to the following masses: 48
      kg, 73 kg, 98 kg, 123 kg, 148 kg, and 173 kg. The effect of size varies with
      photon energy, as might be expected, and at any given energy is an exponential
      function of the mass. An equation has been found that fits most cases very well
      and is still good in poorer cases. Persons lighter in mass than the normal
      calibration phantom (73 kg) will have their body burdens overestimated by as much
      as a factor of 1.3, depending on mass, photon energy, and counting geometry.
      Conversely, heavier individuals will have their body burdens underestimated by as
      much as a factor of 1.9, depending on mass, photon energy, and counting geometry.

PMID- 18617806
TI  - A method to obtain mean organ doses in a RANDO phantom.
AB  - A quantitative method of obtaining average organ dose from point measurements
      made in the male RANDO phantom is described for 24 compact organs of interest in
      patient dosimetry. A three-dimensional Cartesian coordinate system was created by
      considering each of the 36 RANDO phantom sections as the z coordinate, and using
      a rectangular frame to assign x and y coordinates relative to the center of each
      section. Anatomical atlases and clinical experience were used to identify the
      location and extent of each organ and tissue in the RANDO phantom. This proposed
      scheme is comparable to one used in a commercial phantom and offers investigators
      a comprehensive protocol for obtaining mean organ doses in the RANDO phantom.

PMID- 18617807
TI  - A quick and easy method for checking compliance of multi-frequency magnetic
      fields with ICNIRP's guidelines.
AB  - In many practical cases human exposure to extremely low frequency magnetic fields
      with many spectral components (multi-frequency fields) has to be examined in
      order to check compliance with ICNIRP's guidelines. Showing compliance, according
      to existing methods, requires sophisticated instruments and measurement
      procedures to assess some complex exposure metrics. Furthermore, even where the
      field levels are very low, there is no method to show compliance using broadband
      instruments, which are the most common and simple ones. In this paper, a new
      method is described where the frequencies emitted by the source are known and
      only simple broadband instruments are required. First, the spectral distribution
      of the field that maximizes exposure metrics is found. Then, an effective
      reference level for the broadband value of the field is estimated for this
      distribution. If the measured broadband value of the magnetic field is lower than
      this reference level, then compliance with ICNIRP's guidelines is readily shown.
      A case study for a magnetic field consisting of 50 Hz and 60 Hz components is
      presented. The worst-case spectral distribution contained 64% 50 Hz and 76.8% 60
      Hz components, and the corresponding effective broadband reference level is 64
      muT for general public exposure. The method is generally conservative in cases of
      incoherent fields and very conservative in cases of coherent fields. To that end,
      it is practically a quick and easy test to check if further measurements are
      needed or not. Application of this method is expected to save time, money, and
      resources.

PMID- 18617808
TI  - Comment on Al-Azmi et al. Indoor radon in Kuwait.

PMID- 18617813
TI  - Preface: unconscious processes.

PMID- 18617814
TI  - A brief history of sleep and anesthesia.

PMID- 18617815
TI  - Developmental perspectives: is the fetus conscious?

PMID- 18617816
TI  - Are we unconscious during general anesthesia?

PMID- 18617817
TI  - General anesthetics and molecular mechanisms of unconsciousness.

PMID- 18617818
TI  - Loss of effective connectivity during general anesthesia.

PMID- 18617821
TI  - Brain function in physiologically, pharmacologically, and pathologically altered
      states of consciousness.

PMID- 18617822
TI  - Functional neuroimaging of disorders of consciousness.

PMID- 18617820
TI  - Learning and memory during sleep and anesthesia.

PMID- 18617823
TI  - An excitatory path to unconsciousness: nonconvulsive status epilepticus.

PMID- 18617819
TI  - Neurochemical modulators of sleep and anesthetic states.

PMID- 18617825
TI  - Unconscious processes in psychoanalysis and anesthesiology.

PMID- 18617824
TI  - Unconsciousness in the intensive care unit: a practical approach.

PMID- 18617828
TI  - Occupational organic solvent exposure, smoking, and prevalence of chronic
      bronchitis-an epidemiological study of 3387 men.
AB  - OBJECTIVE: To investigate the interaction of smoking and history of long-term
      occupational exposure to organic solvents on the prevalence of chronic bronchitis
      (CB) among middle aged and elderly men. METHODS: A questionnaire on health,
      lifestyle, and working conditions, and a clinical examination including
      measurements of height, weight, and peak-flow. Self-reported occupational solvent
      exposure for 5 years or more was compared to never exposed. Three thousand two
      hundred eight men aged 63 +/- 10 years were included. RESULTS: Four hundred sixty
      one men had CB (14.4%). Current smoking and the interaction of smoking and long
      term occupational exposure to organic solvents (> 5 years) were the factors most
      strongly associated with prevalence of CB. In the solvent exposed group odds
      ratio for CB was 7.0 (95% confidence interval [CI]: 3.4 to 14.5) comparing
      current smokers with non-smokers against only 3.7 (95% CI: 2.8 to 4.8) in the
      nonexposed group, also after control for potential confounders. Among nonsmokers
      only, long-term exposure to organic solvents was not associated with an increased
      prevalence of CB. CONCLUSION: Current or previous occupational exposure to
      organic solvents doubles the smoking related risk of CB, probably due to an
      additional irritative effect in the alveolar and bronchial mucosa.

PMID- 18617829
TI  - Work impact of migraine headaches.
AB  - OBJECTIVE: To estimate work impact of headache among migraineurs. METHODS: Data
      were from a U.S. nationwide mailed questionnaire of 193,477 participants in the
      American Migraine Prevalence and Prevention study. Lost Productive Time (LPT) was
      the sum of missed hours plus reduced productivity hour equivalents. The cause of
      LPT was self-reported. RESULTS: The mean LPT per week was 1.8 hours for headache
      and 2.8 for all health related causes; 76.5% of the headache-related LPT was
      explained by reduced performance (ie, presenteeism). The 29% of migraine cases
      with 11+ headaches-d/mo accounted for 49% of overall LPT; the 19% of those with
      pain score of 9 to 10 on a 0 to 10 scale accounted for 33% of the overall LPT.
      CONCLUSIONS: Individuals with frequent and severe headaches account for a
      disproportionate share of the headache-related LPT.

PMID- 18617830
TI  - The prevalence of psychological distress in employees and associated occupational
      risk factors.
AB  - OBJECTIVE: There is limited occupational health industry data pertaining to 1)
      the prevalence of psychological distress in various employee subtypes and 2) risk
      factors for employee psychological distress. METHOD: The employees of 58 large
      public and private sector employers were invited to complete the Kessler 6 (K6)
      as part of the Health and Performance at Work Questionnaire. A K6 score of > or
      =13 was chosen to indicate high psychological distress. RESULTS: Data on 60,556
      full-time employees indicate that 4.5% of employees have high psychological
      distress of which only 22% were in current treatment. Occupational risk factors
      identified include long working hours, sales staff and non-traditional gender
      roles. CONCLUSION: High psychological distress is pervasive across all employee
      subtypes and remains largely untreated. Risk factors identified will guide the
      targeting of mental health promotion, prevention and screening programs.

PMID- 18617831
TI  - Median and ulnar nerve conduction studies at the wrist: criterion validity of the
      NC-stat automated device.
AB  - OBJECTIVE: To compare results obtained with the NC-stat--an automated nerve
      testing device--to traditional nerve conduction studies relevant to carpal tunnel
      syndrome screening. METHODS: Thirty-three subjects recruited from patients
      referred for electrodiagnostic testing were studied. Measurements including the
      distal motor latency (DML), distal sensory latency (DSL), and median-ulnar
      latency difference (MUD) were obtained by the NC-stat and by standard nerve
      conduction studies. RESULTS: With modifications to the NC-stat's suggested
      reference ranges, sensitivity with respect to the traditional results ranged from
      93.8% (sensory MUD) to 100% (median DML and DSL) and specificity ranged from
      84.6% (motor MUD) to 94.1% (sensory MUD). Sensitivity was as high or higher and
      specificity was lower when using the manufacturer's suggested cutoffs.
      CONCLUSION: The NC-stat appears to be a convenient and sensitive method for
      detecting median nerve pathology at the wrist.

PMID- 18617832
TI  - Effectiveness of a preventive coaching intervention for employees at risk for
      sickness absence due to psychosocial health complaints: results of a randomized
      controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of a preventive coaching intervention on
      sickness absence due to psychosocial health complaints and on general well being
      of employees. METHODS: Employees at risk for sickness absence were identified and
      randomized. The intervention group received the preventive coaching program; the
      control group received usual care. Primary outcome measure of the trial is
      sickness absence due to psychosocial health complaints; secondary outcome
      measures are related to general well being, such as psychological distress,
      fatigue, and coping. RESULTS: No effect of coaching on self-reported sickness
      absence due to psychosocial health complaints was found. The intervention group
      reported statistically significant improved health, declined psychological
      distress, less burnout, less need for recovery, and an increased satisfaction
      with life. CONCLUSIONS: This study shows that the coaching intervention primarily
      has an effect on general well being of employees.

PMID- 18617833
TI  - Breast cancer survivors at work.
AB  - INTRODUCTION: Residual symptoms such as fatigue, cognitive limitations, and
      emotional distress can be experienced by cancer survivors. These symptoms may
      impact their abilities at work. It is unclear to what degree these symptoms are
      associated with work in occupationally active breast cancer survivors, the most
      prevalent cancer survivor group. METHODS: A sample of 100 women working part- or
      full-time with a history of breast cancer and a noncancer comparison group (n =
      103) completed questionnaires related to physical fatigue, depression, anxiety,
      and cognitive limitations. Demographic variables, job stress, type of job, stage
      at diagnosis, treatment exposure, and health behaviors were also measured as
      potential confounders. RESULTS: Four years postdiagnosis breast cancer survivors
      reported higher levels of age-adjusted work limitations (F = 32.708, P < 0.001).
      Significant group by fatigue (beta = -0.311, 95% CI = -0.545 to -0.076) and group
      by depression (beta = 0.331, 95% CI = 0.024 to 0.638) interactions were observed.
      Fatigue was more strongly related to work limitations in the cancer survivor
      group whereas depressive symptoms were more strongly related to limitations at
      work in the noncancer group. Although fatigue accounted for 22% of the variance
      in the model, it explained 71% of the contribution of symptom burden to the
      overall model. CONCLUSIONS: Fatigue was more strongly related to work in the
      breast cancer survivor group after accounting for many potential confounders.
      There is a pressing need to better understand and effectively manage fatigue in
      the workplace in occupationally active breast cancer survivors.

PMID- 18617834
TI  - Combining job stress models in predicting burnout by hierarchical multiple
      regressions: a cross-sectional investigation in Shanghai.
AB  - OBJECTIVE: To compare the predictive validity of the demand control and effort
      reward imbalance model, alone and in combination with each other, for job burnout
      in Shanghai employees. METHODS: A sample of 1368 Shanghai employees responded to
      a core job stress questionnaire and burnout scale in Chinese. Hierarchically
      moderated multiple regressions were used to analyze the relationship between job
      stress and burnout. RESULTS: All factors from both job stress models predicted
      33.5% of the variance in emotional exhaustion, and 20.9% in depersonalization and
      5.5% in personal accomplishment. Factors from the effort-reward model
      demonstrated more power in predicting emotional exhaustion and depersonalization
      than that of demand control model. Personal accomplishment was significantly
      associated with sociodemographic factors. OUTCOME: The combination of two models
      may improve our understanding of the relationship between the psychosocial work
      environment and job burnout.

PMID- 18617835
TI  - Cancer admission and mortality in workers exposed to ionizing radiation in Korea.
AB  - OBJECTIVE: Cancer mortality and morbidity are described for the first time in all
      Korean workers exposed to ionizing radiation. METHODS: Based on hospital
      admissions, Standardized Rate Ratios (SRR) and Standardized Mortality Ratios
      (SMR) were modeled with Poisson regression. RESULTS: Cancer admissions during
      2000 to 2005 were low compared with autoworkers with the exception of nuclear
      power workers (SRR = 1.13, 95% CI = 0.94-1.36). Thyroid cancer was statistically
      significantly elevated in women radiation workers in medical (SRR = 2.90, 95% CI
      = 1.05-7.94) and research institutions (SRR = 3.91, 95% CI = 1.36-11.0) and
      industry (SRR = 5.07, 95% CI = 1.56-15.6), and in all nuclear power workers (SRR
      = 2.59, 95% CI = 1.33-5.13), and there was a significant association with dose
      (ERR = 20.4 per Sv, 90% CI = -8 to 60, one-tailed P = 0.049). The 935 deaths
      revealed a healthy worker effect for all causes (SMR = 0.58, 95% CI = 0.54-0.62)
      and all-cancer (SMR = 0.73, 95% CI = 0.64-0.82). Lung cancer (SMR = 0.77, 95% CI
      = 0.55-1.05) and leukemia (SMR = 0.59, 95% CI = 0.28-1.06) mortalities were also
      less than expected. Compared with autoworkers, radiation workers displayed
      decreased all-cause mortality except for nuclear power workers (statistically not
      significant). CONCLUSIONS: ERRs as high as 300 per Sv appear to be ruled-out in
      this population with regulated exposure to ionizing radiation while ERRs as high
      as 100 per Sv are not.

PMID- 18617836
TI  - Occupational injuries among workers with diabetes: the National Health Interview
      Survey, 1997-2005.
AB  - OBJECTIVE: To assess associations between diabetes and occupational injury.
      METHODS: Data from the 1997 to 2005 National Health Interview Survey comprised a
      sample of 195,284 adult workers. Multivariate logistic regression analysis
      assessed associations between diabetes and occupational injuries, adjusting for
      age, sex, race, and education. Additional logistic regression analysis examined
      the effect of medical therapy and duration of diabetes with occupational injury.
      RESULTS: There was no significant association between diabetes and occupational
      injury (adjusted OR = 1.18; 95% CI = 0.86 to 1.61). Subgroups of diabetics who
      reported no current diabetes therapy (OR = 1.87; 95% CI = 1.01 to 3.47) or
      duration of diabetes longer than 12 years (OR = 1.83; 95% CI = 1.05 to 3.18) were
      at increased risk for occupational injury. CONCLUSION: The finding of no overall
      increased risk for occupational injury among workers with diabetes provides
      nationally representative results that may be useful to policymakers. Increased
      risk for occupational injury among untreated diabetics or those with long
      duration of disease may lead to focused efforts to prevent occupational injuries.

PMID- 18617837
TI  - Comparative and interactive effects of depression relative to other health
      problems on work performance in the workforce of a large employer.
AB  - OBJECTIVES: To present data on the comparative and interactive workplace costs of
      depression relative to other health problems in the workforce of a large
      employer. METHODS: The World Health Organization Health and Work Performance
      Questionnaire was used to assess self-reported health problems and work
      performance. Survey data were linked to medical-pharmacy claims data. Regression
      analysis was used to assess comparative effects of depression in the absence and
      presence of comorbidities on Health and Work Performance Questionnaire measures
      of work performance. RESULTS: Depression had the largest individual-level effect
      on work performance of any condition examined. Several comorbid conditions
      exacerbated the effect of depression, but had no effects in the absence of
      depression. CONCLUSIONS: Depression is a strong predictor of decrements in work
      performance. Other conditions that often co-occur with depression, including
      anxiety and fatigue-sleep disturbance, exacerbate the adverse effect of
      depression.

PMID- 18617838
TI  - Hearing loss among licensed pesticide applicators in the agricultural health
      study.
AB  - OBJECTIVE: We evaluated self-reported hearing loss and pesticide exposure in
      licensed private pesticide applicators enrolled in the Agricultural Health Study
      in 1993 to 1997 in Iowa and North Carolina. METHODS: Among 14,229 white male
      applicators in 1999 to 2003, 4926 reported hearing loss (35%). Logistic
      regression was performed with adjustment for state, age, and noise, solvents, and
      metals. We classified pesticides by lifetime days of use. RESULTS: Compared with
      no exposure, the odds ratio (95% confidence interval) for the highest quartile of
      exposure was 1.19 (1.04 to 1.35) for insecticides and 1.17 (1.03 to 1.31) for
      organophosphate insecticides. Odds of hearing loss were elevated for high
      pesticide exposure events (1.38, 1.25 to 1.54), pesticide-related doctor visits
      (1.38, 1.17 to 1.62) or hospitalization (1.81, 1.25 to 2.62), and diagnosed
      pesticide poisoning (1.75, 1.36 to 2.26). CONCLUSIONS: Although control for
      exposure to noise or other neurotoxicants was limited, this study extends
      previous reports suggesting that organophosphate exposure increases risk of
      hearing loss.

PMID- 18617839
TI  - High prevalence and advanced silicosis in active granite workers: a dose-response
      analysis including FEV1.
AB  - OBJECTIVE: To evaluate silica exposure and respiratory disease in granite
      workers. METHODS: A cross-sectional study of 440 active granite workers. RESULTS:
      Seventy-seven (17.5%) have silicosis, complicated in 15 of them; 18 have an
      obstructive ventilatory defect and 73 had exceeded 3.5 mg/m-year of cumulative
      silica exposure. Percent predicted FEV1 have a significant negative relation with
      mg/m(3)-year (P < 0.001) with a trend toward dose-response excluding silicotics
      and controlling for tobacco. The odds ratio (95% confidence interval) of having a
      percent predicted FEV1 below 50th percentile is 1.18 (0.66 to 2.11) for
      nonexposed smokers, 1.47 (0.76 to 2.84) for exposed nonsmokers, and 2.07 (1.12 to
      3.85) for exposed smokers, in comparison with the control group. CONCLUSIONS:
      This study suggests that silica induces functional alteration regardless of
      silicosis and, in all likelihood, synergistically with tobacco. Exposure levels
      must be controlled better in these workers and those with silicosis must be
      relocated to risk-free jobs or retired.

PMID- 18617840
TI  - Are maternal occupation and residential proximity to industrial sources of
      pollution related?
AB  - OBJECTIVE: We examined the relation between maternal occupation and residential
      proximity to industrial sources of pollution in two case-control study
      populations of birth defects. METHODS: Occupational and residential information
      were obtained from Texas live birth records and maternal interviews of Texas
      participants in the National Birth Defects Prevention Study. Residential
      proximity to industrial sources of air pollution was determined through
      geographic information systems. RESULTS: With adjustment for maternal
      race/ethnicity and education, women in production occupations were twice as
      likely (95% confidence interval 1.3 to 3.0) to reside near these facilities than
      women in management/professional occupations and more likely to reside near such
      facilities than other occupational groups. CONCLUSION: Occupation and residence
      appear related; therefore, both sources of potential exposures may need to be
      considered to understand the relative contribution of either source to risk of
      adverse pregnancy outcomes.

PMID- 18617841
TI  - The relationships between lost work time and duration of absence spells: proposal
      for a payroll driven measure of absenteeism.
AB  - OBJECTIVE: To propose a standard measure of absenteeism (the work lost rate
      [WLR]) be included in future research to facilitate understanding and allow for
      translation of findings between scientific disciplines. METHODS: Hourly payroll
      data derived from "punch clock" reports was used to compare various measures of
      absenteeism used in the literature and the application of the proposed metric (N
      = 4000 workers). RESULTS: Unpaid hours and full absent days were highly
      correlated with the WLR (r = 0.896 to 0.898). The highest percentage of unpaid
      hours (lost work time) is captured by absence spells of 1 and 2 days duration.
      CONCLUSION: The proposed WLR metric captures: 1) The range and distribution of
      the individual WLRs, 2) the percentage of subjects with no unpaid hours, and 3)
      the population WLR and should be included whenever payroll data is used to
      measure absenteeism.

PMID- 18617842
TI  - Protecting health care workers from tuberculosis.

PMID- 18617843
TI  - Workers at height are required to use fall prevention systems. What are the
      health risks from being suspended in a harness?

PMID- 18617847
TI  - Acute inflammatory demyelinating optic neuritis: evidence-based visual and
      neurological considerations.
AB  - BACKGROUND: Optic neuritis (ON) is an acute inflammatory demyelinating disorder
      of the optic nerve that occurs most often in young adults. It can be a monophasic
      or polyphasic disease isolated to the optic nerve(s) or can be associated with a
      more widespread demyelinating disorder of the central nervous system such as
      multiple sclerosis (MS) or neuromyelitis optica. Advances in therapeutics that
      modify the risk of progression to MS have emphasized accurate diagnosis and risk
      assessment of patients with ON. REVIEW SUMMARY: ON usually presents with acute
      unilateral visual loss associated with ocular pain exacerbated by eye movements.
      Similar to results found in studies assessing corticosteroid used in MS relapses,
      intravenous methylprednisolone accelerates visual recovery from ON but has no
      impact on long-term visual outcome. A clinically isolated syndrome (CIS), such as
      ON, is a clinical demyelinating event that is often the initial attack of
      relapsing-remitting MS. Disease modifying drugs, in particular interferons-beta,
      have been shown to reduce the risk of MS conversion in high-risk patients
      presenting with a CIS. The exact timing and patient selection for the initiation
      of treatment remain controversial. CONCLUSION: ON is the best studied CIS. The
      visual prognosis is excellent in most cases regardless of whether the patient is
      treated with corticosteroids or not. Three recently completed prospective,
      randomized, double-blinded, placebo-controlled studies have shown that starting a
      disease-modifying drug at the time of a CIS can reduce the rate of development of
      MS. However, better diagnostic tools are needed to precisely predict the
      conversion to MS and the factors influencing disease severity to determine the
      most appropriate therapeutic paradigm and avoid unnecessary treatment.

PMID- 18617848
TI  - Multiple system atrophy.
AB  - BACKGROUND: It has been almost 4 decades since the descriptions of the 3 parts of
      multiple system atrophy (MSA) have taken place, characterized clinically by
      dysautonomia, parkinsonism, and cerebellar dysfunction. The discovery of a
      distinctive pathologic maker has finally provided the conceptual synthesis of
      these 3 entities into the universal designation of MSA as a distinct disease
      process with a complex combination of clinical presentations. Although advances
      have been made in terms of awareness and knowledge concerning the clinical
      features and pathophysiology of MSA, it remains challenging for neurologists who
      treat these patients to differentiate MSA from its mimics as well as providing
      them with effective treatment. REVIEW SUMMARY: The aim of this review is to
      provide an overview of the advances in the knowledge of the disease, to highlight
      typical features useful for the recognition of its entity, and to enlist
      different treatment options. CONCLUSION: Despite the fact that there is still no
      treatment modality that can alter the disease progression, a number of useful
      symptomatic treatment measures are available and should be offered to patients to
      ameliorate the nonmotor features of MSA and even the motor features that may at
      least transiently respond to treatment.

PMID- 18617849
TI  - The role of uric acid in stroke: the issue remains unresolved.
AB  - BACKGROUND: Although in the past decade a large number of studies have been
      performed to identify the relationship between uric acid and stroke, the issue
      remains unresolved and it is not clear whether the correlation between uric acid
      and stroke is circumstantial or causal. REVIEW SUMMARY: Some studies have found
      uric acid predictive for the development of cardiovascular disease, whereas
      others have failed to identify uric acid as a significant and independent risk
      factor after controlling for other atherosclerotic risk factors. Furthermore,
      uric acid, a powerful endogenous antioxidant, is increased in oxidative stress
      situations such as stroke. Still, it remains controversial whether elevated serum
      uric acid is neuroprotective or injurious at the onset of acute stroke.
      CONCLUSIONS: Large trials are required to provide definite answers in clinical
      practice and to reevaluate the goals of hypouricemic treatment in subjects with
      increased cardiovascular risk or during an acute cardiovascular event like
      stroke. This review tries to keep pace with the data concerning the association
      between uric acid and stroke.

PMID- 18617850
TI  - The promise and potential pitfalls of serum biomarkers for ischemic stroke and
      transient ischemic attack.
AB  - BACKGROUND: Ischemic stroke and transient ischemic attack can be difficult to
      diagnose clinically, and both acute and preventive therapies carry some risk.
      Serum biomarkers could increase diagnostic certainty by helping to distinguish
      cerebral ischemia from common mimics such as focal seizure, complicated migraine,
      and psychogenic spells. Biomarkers could also identify patients at high risk for
      future vascular events, which would aid in management decisions. REVIEW SUMMARY:
      There are many potential obstacles to finding these biomarkers, which are
      reviewed here, including the blood brain barrier, confounding by other
      conditions, and imperfect gold standards for use in validation. Diagnostic
      biomarkers are likely to be molecules found predominantly in brain tissue with
      rapid entry into the blood, whereas risk-stratification biomarkers may be related
      to the concept of an active atherosclerotic plaque. Many promising serum
      molecules have been examined in small series of patients with cerebrovascular
      disease. CONCLUSION: Large series examining many candidate molecules will be
      needed to find valid biomarkers, and this should be followed by use in future
      intervention trials to prove their utility.

PMID- 18617851
TI  - Profile of central nervous system disease in HIV/AIDS patients with special
      reference to cryptococcal infections.
AB  - OBJECTIVES: Central nervous system involvement is common in acquired
      immunodeficiency syndrome (AIDS), with Cryptococcus neoformans being an important
      cause among etiologies causing fungal meningitis. Seventeen human
      immunodeficiency virus (HIV)-positive adults with symptoms of chronic meningitis
      were investigated for fungal meningitis because of C. neoformans and a
      correlation was attempted with the CD4 counts of these patients. METHODS:
      Cerebrospinal fluid and blood samples were collected for direct microscopy,
      culture, and serology. CD4 counts were determined by flow cytometry. RESULTS:
      Cryptococcal meningitis was seen in 5 (29.4%) patients, tubercular meningitis in
      9 (52.9%) patients, HIV encephalopathy in 2 (11.7%), and cerebral toxoplasmosis
      in 1 patient. In patients with Cryptococcal meningitis both methods, ie, an India
      ink preparation and Gram staining gave similar results. Culture was positive in 3
      patients (60%) whereas Cryptococcal antigen in cerebrospinal fluid was positive
      in 4 (80%) patients. The mean CD4 count was 120 +/- 55.13 cells/microL.
      CONCLUSION: The study provides information about the increasing incidence of
      Cryptococcal meningitis after the AIDS pandemic. It indicates progression of HIV
      infection toward AIDS and is useful as a reference to starting antiretroviral
      therapy in settings where facilities for determination of CD4 counts are not
      available. It also confirms that the course of Cryptococcal meningitis in Indian
      patients is similar to most studies.

PMID- 18617852
TI  - Brain injury due to ventricular shunt placement delineated by diffusion tensor
      imaging (DTI) tractography.
AB  - OBJECTIVE: Infection and hemorrhage are well-known complications from insertion
      of intracranial shunts. However, permanent injury to the brain caused by
      catheterization of the cerebral ventricles has rarely been reported. METHODS: We
      report a patient who presented at age 14 years for evaluation of a severe
      behavioral disorder. The patient had sustained direct injury to the corticospinal
      tract and limbic system during revision of a ventriculoperitoneal shunt at the
      age of 9 years. RESULTS: Despite persistent evidence of severe disruption of the
      corticospinal tract on diffusion tensor imaging at age 14 years, the patient had
      regained complete motor function. CONCLUSION: Recovery of motor function after
      serious injury to motor cortex during childhood is a dramatic example of the
      plasticity of the child's brain to injury. In addition, we suggest that the
      behavioral disorder that emerged in this patient may be related to limbic system
      injury suffered during the shunt revision.

PMID- 18617853
TI  - Limbic encephalitis with involvement of prefrontal cortices and persistent
      amnesia.
AB  - OBJECTIVES: Most abnormalities on magnetic resonance imaging (MRI) in limbic
      encephalitis involve the medial temporal lobes and are associated with memory
      impairment. Recent neuroimaging studies have shown that not only the medial
      temporal lobes, but also the prefrontal lobes, contribute to cognitive functions.
      METHODS: We describe a case of limbic encephalitis with abnormalities in the
      medial temporal lobes on MRI and decreased accumulation of radionuclide in the
      prefrontal regions on SPECT. RESULTS: The patient had persistent retrograde
      amnesia, particularly affecting remotely acquired memories including public
      events and autobiographical memories. CONCLUSION: Disruption of the prefrontal
      medial temporal circuitry by intense inflammation may have initiated the
      metabolic changes in the prefrontal cortices, which may exacerbate amnesia.

PMID- 18617854
TI  - Hemiparkinsonism secondary to an infiltrative astrocytoma.
AB  - BACKGROUND: Brain tumors are uncommon etiologies of parkinsonism. The clinical
      manifestations of tumoral parkinsonism may sometimes resemble those of idiopathic
      origin. Increased awareness of this rare entity is important for an earlier
      prompt diagnosis and treatment. REVIEW SUMMARY: A previously healthy, 60-year-old
      man developed slowly progressive right-sided resting tremor and bradykinesia over
      8 months. Although idiopathic Parkinson disease was the initial diagnosis, the
      parkinsonian symptoms were not responsive to medical treatment with levodopa and
      a dopamine agonist. Brain computed tomography failed to reveal an intracranial
      lesion. Brain magnetic resonance imaging demonstrated an infiltrative, slightly
      enhancing mass in the left mesial temporal lobe extending to the left basal
      ganglion and insula. Histopathologic findings confirmed the diagnosis of high
      grade astrocytoma. The parkinsonian symptoms subsided after tumor removal;
      however, ipsilateral hemiparesis developed postoperatively. CONCLUSIONS:
      Neuroimaging is recommended for investigation of atypical parkinsonism. We
      suggest that brain magnetic resonance imaging is preferred for patients with drug
      resistant parkinsonism or concurrent signs apart from extrapyramidal symptoms,
      because some mass lesions are not observed by computed tomography scan.

PMID- 18617855
TI  - 10 questions about statins and stroke.

PMID- 18617856
TI  - Clinical predictors of psychogenic nonepileptic seizures: a critically appraised
      topic.
AB  - BACKGROUND: Psychogenic nonepileptic seizures (PNES) are often disabling and
      usually associated with psychiatric disorders and reduced quality of life.
      Although often suspected based on historical and clinical features, the gold
      standard for diagnosis of PNES is video electroencephalography. Identification of
      clinical features that reliably distinguish PNES from ES would be valuable in
      acute care settings, for patients that have coexisting disorders, and those with
      multiple event types. OBJECTIVE: To determine the diagnostic value of putative
      clinical symptoms or signs of PNES against the gold standard of video
      electroencephalography. METHODS: We addressed the objective through development
      of a structured critically appraised topic that included a clinical scenario,
      structured question, search strategy, critical appraisal, results, evidence
      summary, commentary, and bottom-line conclusions. Participants included
      consultant and resident neurologists, a medical librarian, clinical
      epidemiologists, and content experts in the field of epileptology. RESULTS: There
      were wide variations in the rates of coexisting PNES and epilepsy and study
      methodology. Ictal stuttering and the "teddy bear" sign were associated with
      moderate specificity for PNES. However, the presence of pelvic thrusting or ictal
      eye closure did not accurately distinguish PNES from ES. CONCLUSIONS: The
      presence of either ictal stuttering or the teddy bear sign is moderately specific
      but poorly sensitive for PNES. Pelvic thrusting and ictal eye closure are not
      reliable indicators of PNES. Future studies should establish more precise and
      reliable definitions of clinical signs and evaluate combinations of such signs in
      a broad spectrum of patients with PNES and ES spell phenotypes that may be
      difficult to distinguish, such as spells of unresponsiveness with motor
      manifestations. Because PNES and ES may coexist, analysis of diagnostic accuracy
      of clinical features should be performed for individual spells.

PMID- 18617857
TI  - Patient and family fact sheet. Epilepsy surgery.

PMID- 18617858
TI  - Clinical evaluation and treatment of posterior impingement in dancers.
AB  - Os trigonum impingement is a frequent cause of posterior ankle pain in ballet
      dancers because they need extreme plantar flexion during the execution of releve
      in demipointe and en pointe positions. Clinical examination and standard and
      modified x-rays should be carried out to clearly identify the site and entity of
      the impingement. If a posterior impingement is clinically diagnosed, standard and
      modified magnetic resonance imaging should be also performed. From September 2005
      to September 2006, we considered 186 young trainee ballet dancers. Twelve
      suffered from posterior ankle pain, and six of these had os trigona. We treated
      all the ballet dancers nonoperatively, and nine of them had good results.
      Conservative treatment failed in only three cases after 1-4 mos of physical and
      medical therapies, and, in these cases, good results were obtained through
      surgical excision of the accessory ossicle. Modified x-ray and magnetic resonance
      imaging help to determine the site and entity of the posterior impingement. If
      this is properly diagnosed, good results can be obtained through a nonoperative
      approach in a majority of cases.

PMID- 18617859
TI  - Anatomic localization of motor points for the neuromuscular blockade of hand
      intrinsic muscles involved in thumb-in-palm.
AB  - OBJECTIVE: To determine the location of the motor points and intramuscular
      branches for the muscles involved in thumb-in-palm and the abductor pollicis
      brevis muscle, the latter of which, because of its anatomic proximity, may be
      inadvertently blocked. DESIGN: Hand intrinsic muscles from 20 fresh cadavers were
      dissected. The point of nerve entry to the muscle belly and the points where the
      intramuscular endings were located most proximally and distally were defined in
      relation to a reference line connecting the hook of hamate and the head of the
      first metacarpal bone. RESULTS: We were able to define a region, located from
      66.08% +/- 8.67% to 70.28% +/- 10.62% of the reference line, with the hook of
      hamate as starting point, where intramuscular endings for the thumb-in-palm
      muscles were dense and farther from the intramuscular endings for the abductor
      pollicis brevis. The region around 40% of the reference line was the point where
      the intramuscular endings were most dense for the abductor pollicis brevis.
      CONCLUSION: The results may provide guidelines that could help in localizing the
      appropriate points for the neuromuscular blockade of thumb-in-palm muscles and,
      at the same time, help in minimizing the inadvertent block of the abductor
      pollicis brevis.

PMID- 18617860
TI  - Robotic therapy and botulinum toxin type A: a novel intervention approach for
      cerebral palsy.
AB  - The combined effects of robotic therapy and botulinum toxin type A (BTX-A) on
      upper-limb movement and function were studied in an 8(1/2)-yr-old child with
      hemiplegic cerebral palsy. Robotic therapy comprising repetitive, goal-directed
      reaching tasks was administered two times per week for 8 wks. Clinical measures
      included the Modified Ashworth Scale, the Quality of Upper Extremity Skills Test,
      and the Fugl-Meyer Assessment (upper-limb section). Improvements in upper-limb
      coordination and quality of motor performance were apparent throughout the
      robotic therapy trial. The observed gains are comparable with those attained from
      conventional occupational therapy combined with BTX-A. A parent questionnaire
      indicated that the amount of paretic arm use also improved during daily
      activities at home. This preliminary study indicates that robotic therapy may be
      a useful clinical tool when combined with BTX-A injections for improving upper
      limb coordination and quality of motor performance in children with cerebral
      palsy.

PMID- 18617861
TI  - Electrophysiologic effects of a therapeutic laser on myofascial trigger spots of
      rabbit skeletal muscles.
AB  - OBJECTIVE: To better understand the mechanisms of therapeutic lasers for treating
      human myofascial trigger points, we designed a blinded controlled study of the
      effects of a therapeutic laser on the prevalence of endplate noise (EPN) recorded
      from the myofascial trigger spot (MTrS) of rabbit skeletal muscle. DESIGN: In
      eight rabbits, one MTrS in each biceps femoris muscle was irradiated with a 660
      nm, continuous-wave, gallium-aluminum-arsenate (GaAlAs) laser, at 9 J/cm2. The
      contralateral side of muscle was treated with a sham laser. Each rabbit received
      six treatments. The immediate and cumulative effects were assessed by the
      prevalence of EPN with electromyographic (EMG) recordings after the first and
      last treatments. RESULTS: Compared with pretreatment values, the percentages of
      EPN prevalence in the experimental side after the first and last treatments were
      significantly reduced (P < 0.01 for both). The change in EPN prevalence in the
      experimental side was significantly greater than in the control side immediately
      after the first and last treatments (P < 0.05). However, no significant
      differences were noted between the first and last treatments (P > 0.05).
      CONCLUSIONS: In our study, immediate and cumulative effects of a GaAlAs laser
      applied on MTrS were demonstrated on the basis of the assessment of EPN
      prevalence. It seems that laser irradiation may inhibit the irritability of an
      MTrS in rabbit skeletal muscle. This effect may be a possible mechanism for
      myofascial pain relief with laser therapy.

PMID- 18617862
TI  - Pneumothorax associated with mechanical insufflation-exsufflation and related
      factors.
AB  - Impaired cough that results in ineffective airway secretion clearance is an
      important contributor to pulmonary complications in patients with neuromuscular
      weakness including spinal cord injury. Mechanical insufflation-exsufflation (MI
      E) is a respiratory aid used by patients with weak respiratory muscles to
      increase cough peak flows and improve cough effectiveness. Relative
      contraindications to MI-E are said to include susceptibility to pneumothorax, but
      the association of pneumothorax with MI-E use has never before been described. We
      report two cases of pneumothorax in patients with respiratory muscle weakness
      associated with daily use of MI-E: one was a 58-yr-old male with C4 ASIA C
      tetraplegia, and the other was a 26-yr-old male with Duchenne muscular dystrophy.
      Both patients also used positive-pressure ventilatory assistance. Although
      seemingly rare in this patient population, ventilator users also using MI-E who
      have increasing dyspnea or who require increasing positive inspiratory pressures
      when using noninvasive ventilation should be evaluated for pneumothorax.

PMID- 18617863
TI  - Effects of an anterior ankle-foot orthosis on postural stability in stroke
      patients with hemiplegia.
AB  - OBJECTIVE: To evaluate the effects of an anterior leaflet ankle-foot orthosis
      (AFO) on postural stability in stroke patients with hemiplegia. DESIGN: Twenty
      one stroke patients with hemiplegia resulting from new-onset stroke and ten
      normal subjects were included in this study. The SMART balance master system was
      used to assess the postural stability by measuring the ankle strategy, maximal
      stability, and velocity of center-of-gravity (COG) movement under the following
      six conditions: (1) eyes open and fixed support (EOFS), (2) eyes closed and fixed
      support (ECFS), (3) sway-referenced vision and fixed support (SVFS), (4) eyes
      open and sway-referenced support (EOSS), (5) eyes closed and sway-referenced
      support (ECSS), and (6) sway-referenced vision and support (SVSS). Each patient
      was tested with and without an anterior AFO as compared with normal subjects.
      RESULTS: When wearing an anterior AFO, patients used ankle strategy more than hip
      strategy to maintain postural stability in all the six sensory conditions (P <
      0.05). An anterior AFO also provided stroke patients with better maximal
      stability under relatively challenging conditions such as SVFS, EOSS, and ECSS (P
      < 0.05), but the effect was not apparent in the conditions without external
      perturbation (EOFS and ECFS) and the most difficult condition (SVSS). The
      velocity of COG movement was lowered when wearing an anterior AFO in stroke
      patients, and significant differences existed in the EOFS, ECFS, ECSS, and SVSS
      conditions (P < 0.05). CONCLUSIONS: In the early stage of recovery, the use of an
      anterior AFO may assist stroke patients with hemiplegia to improve their postural
      stability.

PMID- 18617864
TI  - Pulmonary edema after electroconvulsive therapy.
AB  - A 42-year-old right-handed man with major depression, posttraumatic stress
      disorder, gastroesophageal reflux disease, and hypertension received 7 treatments
      of right unilateral electroconvulsive therapy, with the only complications being
      elevated blood pressure up to 180/120 mm Hg and agitation upon awakening. During
      eighth treatment, he experienced blood pressures as high as 210/130 mm Hg with
      severe agitation upon awakening from anesthesia followed by pulmonary edema.
      Pulmonary edema is rarely seen as a complication in electroconvulsive therapy,
      but if the airway becomes obstructed or there is excessive sympathetic discharge
      during the procedure, pulmonary edema may be more likely to occur.

PMID- 18617865
TI  - Safety of electroconvulsive therapy in psychiatric patients shortly after the
      occurrence of pulmonary embolism.
AB  - We encountered 2 patients with a psychiatric disorder (depression in one and
      catatonia in one) accompanied by motor inhibition that was complicated by
      pulmonary embolism (PE). In both cases, the psychiatric disorder was safely
      resolved with electroconvulsive therapy (ECT) during anticoagulant therapy. The 2
      cases direct our attention to at least 3 important points regarding safe
      administration of ECT shortly after the occurrence of PE, that is, careful
      evaluation of cardiac function and residual deep vein thrombosis before the start
      of an ECT course, adjustment of anticoagulants, and prevention of recurrent deep
      vein thrombosis and PE by methods in addition to anticoagulant therapy (fluid
      infusion, use of support hose, and timely ECT).

PMID- 18617866
TI  - The safety of the electroconvulsive therapy-escitalopram combination.
AB  - It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the
      treatment of major depressive episodes may be enhanced by concurrent
      administration of antidepressant medication. Therefore, the issue of how safe the
      combination of these 2 treatment modalities is warrants investigation.
      Escitalopram (ESC) is a novel selective serotonin reuptake inhibitor that seems
      to have a favorable side effect profile. To the best of our knowledge, there is
      no report on the safety of the ECT-ESC combination. We report the cases of 3
      female inpatients with major depressive episode--two in the context of major
      depressive disorder and one in the context of bipolar disorder I--who underwent
      ECT while concurrently receiving ESC (20 mg/d) as part of their regimen. In all
      cases, the combination was well tolerated, and only minimal side effects were
      reported.

PMID- 18617867
TI  - Yoga: an evidence-based prescription for menopausal symptoms?

PMID- 18617868
TI  - The effect of the Meniett device in patients with Meniere's disease: long-term
      results.
AB  - OBJECTIVE: To review our long-term experience with the Meniett device in patients
      who failed medical management to analyze its efficacy in controlling vertigo and
      its impact on the functional level of the patient. STUDY DESIGN: Retrospective
      case review with long-term follow-up of patients receiving the Meniett device at
      our institution between May 2002 and April 2005. SETTING: Tertiary referral
      center. PATIENTS: Patients who failed medical therapy for Meniere's disease and
      opted to receive the Meniett over chemical labyrinthectomy, surgical
      labyrinthectomy, endolymphatic shunt surgery, or vestibular nerve section.
      INTERVENTION: The Meniett is a small, portable, low-pressure pulse generator
      meant to be self-administered, requiring 5-minute sessions 3 times a day. MAIN
      OUTCOME MEASURE: Patient's current perception of usefulness of Meniett device for
      controlling vertigo and current level of Meniett treatment. RESULTS: Of 14
      patients meeting the study criteria, 12 were able to be contacted, giving an
      average follow-up of 4 years. Three patients (25%) showed no benefit; 9 patients
      (75%) did respond to the Meniett and thought it had reduced the frequency and
      severity of their vertigo attacks. Seven patients (58%) continued to use the
      device on a daily basis; the other 2 patients (17%) went into remission 2 and 3
      years after initiating treatment. CONCLUSION: The Meniett device is a minimally
      invasive, nondestructive treatment that may be used to provide longer-term
      reduction of vestibular symptoms in patients with Meniere's disease.

PMID- 18617869
TI  - Newborn hearing screening in infants with cleft palates.
AB  - OBJECTIVE: The high incidence of conductive hearing loss from serous effusion in
      patients with cleft palate is well known. This study investigates the results and
      interpretation of newborn hearing screening in infants with cleft palates. STUDY
      DESIGN: Retrospective cohort review. PATIENTS: One hundred fourteen newborns with
      cleft palate, with or without cleft lip, born between 1999 and 2005 and referred
      to a craniofacial anomalies clinic. INTERVENTION: Tympanostomy tubes were placed
      in 102 newborns, and follow-up audiograms were available for 104 infants. MAIN
      OUTCOME MEASURES: Hearing screening outcomes were collected. Sex, gestational
      period, type of screening performed, the presence of hearing loss after tube
      placement, and the presence of associated syndromes were noted. RESULTS: Eighty
      two (72%) of 114 of newborns with cleft palates passed their hearing screen. Of
      the 30 newborns who failed their hearing screen, and had tympanostomy tubes
      placed, 13 (43%) had persistent hearing loss after tube placement. Factors
      predicting persistent hearing loss include cleft palate alone, female infants,
      and the presence of an associated syndrome. CONCLUSION: Newborns with cleft
      palate are at higher risk of failing their newborn hearing screen compared with
      healthy neonates. Detection of sensorineural or conductive hearing loss unrelated
      to middle ear effusions is more difficult in this at-risk population with cleft
      palate because of the high prevalence of serous otitis media.

PMID- 18617870
TI  - A systematic review of diagnostic criteria for acute mastoiditis in children.
AB  - OBJECTIVE: To review systematically the literature for the current criteria and
      strategies used to diagnose acute mastoiditis in children. METHOD: A
      comprehensive literature search was performed in PubMed, Embase, and the Cochrane
      Library of studies on the diagnosis of acute mastoiditis in children published
      between January 1980 and September 2007. The study type and setting, diagnostic
      criteria for acute mastoiditis, disease-specific history, presenting otologic and
      systemic signs and symptoms, diagnostic procedures, and final diagnosis were
      identified. RESULTS: The initial search resulted in 1,057 articles. The inclusion
      criteria were met in 65; 44 were retrospective case series, and 21 were case
      reports. These studies included 2,109 children with a median age of 32 months
      (range, 0 mo-18 yr). Only 26 of 65 articles reported the criteria upon which the
      diagnosis of acute mastoiditis in children was based. The criteria most
      frequently used were the clinical signs of postauricular swelling, erythema,
      tenderness, and protrusion of the auricle. The most frequently used imaging
      modality was computed tomographic (CT) scanning (reported in 39 of 65 studies,
      performed in 68% of patients). The most frequently used laboratory test was white
      blood count (100% of patients in 45 of 65 studies). In 63 studies, the result of
      culturing from the otomastoid was reported: Streptococcus pneumoniae was the most
      frequently isolated bacterium. CONCLUSION: Acute mastoiditis in children is an
      entity that is poorly evaluated and understood in the modern literature. There is
      a lack of consensus regarding the criteria and strategies for diagnosing acute
      mastoiditis in the pediatric population. It is crucial that such criteria are
      established, and consensus is achieved so that prognostic and controlled studies
      can be initiated to identify risk factors and establish the most effective
      management of this condition in children.

PMID- 18617871
TI  - Evaluation of quality of life after intratympanic streptomycin injection in
      patients with Meniere's disease.
AB  - OBJECTIVES: Quality of life (QOL) and satisfaction level of patients with
      Meniere's disease who underwent intratympanic streptomycin injection were
      evaluated across physical, psychological, and social domains of function. STUDY
      DESIGN: Preoperative and postoperative QOL of patients were evaluated based on
      the chart records of patients and questionnaire surveys. From January 2000 to
      August 2005, 81 patients underwent intratympanic streptomycin injection at Yonsei
      University Severance Hospital, and their medical records were retrospectively
      reviewed. In addition, a mailed questionnaire survey was conducted. Meniere's
      Disease Outcome Questionnaire-Retrospective Version, proposed by Kato et al., was
      used as the QOL measure and was completed by 51 patients. RESULTS: The average
      QOL score was 35.6 +/- 9.6 before surgery and 52.8 +/- 10.3 after surgery,
      indicating improvement of QOL by 17.2 after surgery. The improvement of QOL score
      did not correlate to age and sex of patients; nonetheless, higher improvement of
      score was found in patients with professional career (p < 0.001). The improvement
      of QOL in the preoperative Stage 3 and 4 patient groups was greater than that in
      the preoperative Stage 1 and 2 patient groups (p = 0.032). The mean change in
      hearing of the patients after surgery was 1.5 + 7.2 dB hearing loss based on a 4
      frequency pure-tone average (500, 1,000, 2,000, 3,000 Hz). Furthermore, 4 (7.8%)
      of 51 patients demonstrated greater than 10-dB change in 4-frequency pure-tone
      average. The status of hearing loss after surgery did not influence the QOL score
      (p = 0.530). As the frequency of vertigo decreased, the improvement of QOL score
      increased (p = 0.042). CONCLUSION: The level of satisfaction with intratympanic
      streptomycin injection was strongly correlated to the QOL score in Meniere's
      Disease Outcome Questionnaire-Retrospective Version. As for the factors that
      improved the QOL after surgery, the status of hearing was not closely associated;
      however, the frequency of vertiginous symptom was the most important factor.

PMID- 18617872
TI  - Lubiprostone (Amitiza) for irritable bowel syndrome with constipation.

PMID- 18617873
TI  - Varenicline (Chantix) warnings: risk versus benefit.

PMID- 18617874
TI  - Wellbutrin versus generic bupropion.

PMID- 18617875
TI  - The EarCheck Middle Ear Monitor for detection of middle ear effusion in children.

PMID- 18617876
TI  - Morbidity of salivary gland digital sialography using a non-ionic dimeric
      contrast medium.
AB  - AIM: Sialography is considered a low invasive procedure, due to cannulation of
      salivary duct orifice. The aim of this study was to evaluate the morbidity of
      sialography using a nonionic dimeric contrast medium. METHODS: A questionnaire
      was proposed to 90 patients who underwent parotid and submandibular sialography
      to reveal related symptoms as: pain, swelling, impairment to daily activities and
      taste alteration. Pain and swelling intensity was assessed using a visual
      analogue scale (VAS). RESULTS: Fifty-two out of ninety questionnaires were
      returned. Sialography was performed in 30/52 patients in the submandibular gland,
      22/52 in the parotid gland. Pain during sialography was complained by 28/52
      patients with a 2.4 mean VAS score. Pain after sialography, was reported by 17/52
      patients with a 1.3 mean VAS score. Swelling was reported by 25/52 patients with
      a 2.4 mean VAS score; 48/52 patients returned immediately to daily activities;
      8/52 complained different taste alterations. CONCLUSION: Main related symptoms
      for submandibular and parotid sialography are pain and swelling, spontaneously
      resolving after 24-48 hours in most of cases. The statistical analysis also
      demonstrated in patients who underwent submandibular sialography the onset of
      pain during the procedure is significantly related to an increase of pain after
      the examination. Thus in patients, who referred severe pain during sialography,
      antiinflammatory drugs are recommended to control the onset of pain after
      sialography.

PMID- 18617877
TI  - Marginal adaptation and microleakage of five root-end filling materials: an in
      vitro study.
AB  - AIM: Endodontic surgery consists of several procedures which involve the
      endodontic space or the root canal and is performed as an alternative to
      unsuccessful outcomes or complications following endodontic treatments. The aim
      of the study was to evaluate the sealing ability of five root-end filling
      materials. METHODS: Fifty human single rooted teeth were treated endodontically;
      roots were resected at 3 mm from the apex, and root end cavities were prepared
      with ultrasonic tips. Root ends were filled with one of the following materials:
      silver amalgam (control group); mineral trioxide aggregate; white Portland
      cement; Vitremer; and Fuji Ortho. Apical sealing was evaluated by evaluating
      microleakage of 50% silver nitrate solution. The apical portion of the roots was
      sectioned to obtain 1-mm thick transversal slices, and epoxy resin replicas of
      these apical slices were produced. A scanning electron microscope (SEM) was used
      for analyses. The Kruskal-Wallis test and a multiple comparisons test were used
      for statistical data analysis. RESULTS: Results showed microleakage and variable
      adaptation gaps on the interface between dentin and root-end filling material in
      all specimens. CONCLUSION: All the studied materials exhibited some degree of
      apical microleakage and marginal gaps. No correlation was found between data
      obtained from analyses of apical sealing and marginal adaptation.

PMID- 18617878
TI  - Effect of incisal tooth wear and restoration on interocclusal distance during
      Brazilian Portuguese language speech.
AB  - AIM: The aim of this study was to investigate changes in interocclusal distance
      (IOD) during pronunciation of /m/ and /s/ sounds in Brazilian Portuguese, in
      patients presenting dental wear due to bruxism, before and after placement of a
      stabilization appliance and restorative treatment. METHODS: Subjects were divided
      into a control group of 19 patients with no dental wear and an experimental group
      of 18 patients presenting dental wear on anterior teeth due to bruxism. A
      stabilization appliance was placed in each patient in the experimental group and
      anterior teeth were restored. A magnetic jaw-tracking device measured the
      interocclusal distance during pronunciation of /m/ and /s/ phonemes.
      Interocclusal distance for the experimental group was evaluated one week before
      and again immediately before the appliance was inserted and 24 hours, 7 days, 1
      month and 2 months after appliance insertion. The same evaluation was performed 7
      days and 1 month after restorative treatment. In the control group, the
      measurements were carried out at the same intervals. RESULTS: Comparison between
      groups revealed a significant difference (P<0.05) in interocclusal distance for
      the /m/ sound at all evaluation intervals. No differences were found before and
      after appliance insertion and restorative treatment with either phoneme.
      CONCLUSION: Stabilization appliance therapy and restorative treatment of subjects
      with dental wear did not change the interocclusal distance during speech of /m/
      and /s/ sounds in the Brazilian Portuguese language, however, when compared with
      normal subjects, the IOD values were higher for the dental wear group during
      pronunciation of the /m/ sound.

PMID- 18617879
TI  - A familial case of popliteal pterygium syndrome.
AB  - Popliteal pterygium syndrome (PPS) is a rare malformation disorder characterized
      by autosomal dominant inheritance, highly variable expressivity and incomplete
      penetrance. The disorder is caused by the mutation of the IRF6 gene and the
      respective protein, which belongs to a family of nine transcription factors and
      is involved in the differentiation and proliferation of keratinocytes. Mutations
      in the IRF6 gene give rise to popliteal pterygium syndrome, Van Der Woude
      syndrome and nonsyndromic orofacial clefts. The anomalies from which affected
      patients suffer can be subdivided into alterations of the orofacial region, the
      musculoskeletal system and the genitals. Diagnosis is difficult, as is
      differential diagnosis, due to the variability of the manifestations. Prenatal
      diagnosis is possible by means of sequence analysis of the IRF6 gene in DNA
      extracted from the chorionic villus or amniotic fluid, or by means of
      intrauterine ultrasound. The prognosis is generally good, with normal mental
      development and the possibility to correct most of the alterations through
      targeted surgery. The case presented in this study involves two patients: a
      father and daughter who suffer from PPS, of whom the former was not diagnosed at
      birth. The two patients have undergone numerous operations over the years on
      various parts of the body and sequence analysis of the IRF6 gene, which revealed
      the presence of a mutation in the target site.

PMID- 18617880
TI  - Mandibular osteomyelitis due to Pseudomonas aeruginosa. Case report.
AB  - Osteomyelitis is a relatively frequent bacterial infection of the jaw bones. This
      report describes a case of mandibular osteomyelitis in a surgical site after
      enucleation of a follicular cyst and extraction of the associated tooth. This
      case is unusual because maxillary osteomyelitis generally results from
      polymicrobial infection. In our patient, however, laboratory analysis identified
      Pseudomonas aeruginosa as the etiologic agent, an opportunistic pathogen normally
      found on moist surfaces and vegetation. Notorious for its antibiotic
      multiresistance, P. aeruginosa is increasingly recognized as a serious problem in
      hospitalized patients. Isolation of the responsible microbe permitted specific
      antibiotic treatment with a 10-day course of ciprofloxacin (250 mg/12 h), which
      fully cleared the infection.

PMID- 18617881
TI  - Relationship between arterial stiffness and myocardial damage in patients with
      newly diagnosed essential hypertension.
AB  - BACKGROUND: Arterial stiffness increases in hypertensive individuals. Arterial
      stiffness is associated with impairment of systolic and diastolic myocardial
      function in hypertension (HT). However, the relationship between arterial
      stiffness and serum heart-type fatty acid-binding protein (H-FABP) levels, a
      sensitive marker of myocardial damage, has not been previously examined in
      patients with HT. We investigate the relationship between serum H-FABP levels and
      arterial stiffness in patients with newly diagnosed HT. METHODS: We studied 46
      (48.5 +/- 10.6, years) never-treated patients with HT and age-matched control
      group of 40 (47 +/- 8.6, years) normotensive individuals. H-FABP levels were
      determined in all subjects. We evaluated arterial stiffness and wave reflections
      of study population, using applanation tonometry (Sphygmocor). Carotid-femoral
      pulse wave velocity (PWV) was measured as indices of elastic-type, aortic
      stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as
      a marker of wave reflections. RESULTS: Carotid-femoral PWV (10.5 +/- 2.2 vs. 8.7
      +/- 1.6, m/s, P = 0.0001) and AIx@75 (22.7 +/- 9.5 vs. 15 +/- 11, %, P = 0.001)
      were significantly higher in patients with HT than control group. H-FABP levels
      were increased in hypertensive patients compared with control group (21.1 +/-
      14.8 vs. 12.9 +/- 8.5, ng/ml, P = 0.002). In multiple linear regression analysis,
      we found that the body mass index (beta = 0.42, P = 0.0001) and carotid-femoral
      PWV (beta = 0.23, P = 0.03) were significant determinants of H-FABP levels.
      CONCLUSION: Arterial stiffness is associated with serum H-FABP levels, a
      sensitive marker of myocardial damage, in patients with newly diagnosed HT.

PMID- 18617882
TI  - Gender-related differences in the relationships between blood pressure, age, and
      body size in prepubertal children.
AB  - BACKGROUND: The blood pressure (BP) increase with age is well documented in
      adults and children. However, in the pediatric age group, body size is the most
      important determinant of age-related BP increases. The aim of the present
      analysis was to investigate the relationships between age, gender, and body size
      and BP in children. METHODS: To this purpose, data were analyzed from 4,514
      prepubertal children, aged 6-11 years (71% of the eligible sample; boys = 2,283,
      girls = 2,231) from the ARCA Project, a screening of childhood obesity carried
      out in southern Italy. Girls who reported the occurrence of menarche were
      excluded from the analysis. The sample constituted roughly 20% of all the
      children attending the primary schools in the area. Weight, height, waist
      circumference, and BP were measured according to standardized procedures.
      RESULTS: As expected, both systolic and diastolic BP significantly increased (P <
      0.001) with age in boys and girls. However, after adjustment for waist
      circumference (as index of adiposity) and height (as index of body size), BP
      significantly increased with age only in girls (systolic BP: F = 4.380, P =
      0.002; diastolic BP: F = 3.093, P = 0.01) but not in boys (systolic BP: F =
      0.711, P = 0.55; diastolic BP: F = 2.180, P = 0.07). The association, however,
      was no longer apparent after the exclusion of children aged >10 years.
      CONCLUSIONS: In prepubertal girls in the age range 6-11 years, but not in boys,
      age is significantly associated with BP independently of body size and adiposity.

PMID- 18617883
TI  - Gender disparities in hypertension among different ethnic groups in Amsterdam,
      The Netherlands: the SUNSET study.
AB  - BACKGROUND: Studies have consistently shown a lower prevalence of hypertension in
      women than in men. Obesity is an important risk factor for hypertension, and the
      rate of obesity is particularly high among ethnic minority women. It is therefore
      questionable whether the lower prevalence of hypertension in women is also true
      among specific ethnic minority groups in Europe. Hence, we sought to determine
      whether gender disparity in hypertension is consistent across different ethnic
      groups, and if not so, whether differences in body sizes (body mass index (BMI)
      and waist circumferences) explain demonstrated gender disparities in hypertension
      among different ethnic groups in Amsterdam, the Netherlands. METHODS: The SUNSET
      study was a random sample of 1,432 people aged 35-60 years (508 White-Dutch, 591
      African-Surinamese, and 333 Hindustani-Surinamese). RESULTS: Age-adjusted
      hypertension rate was significantly lower in White-Dutch women than in White
      Dutch men as expected--the odds ratio (95% confidence interval) was 0.35 (0.23
      0.54). This difference hardly changed after adjustment for body sizes and other
      factors. However, among the ethnic minority groups, age-adjusted hypertension
      rate did not differ significantly between women and men in both African
      Surinamese 0.74 (0.51-1.08) and Hindustani-Surinamese 0.80 (0.49-1.29). It was
      only after further adjustment for body sizes that African-Surinamese women were
      significantly less likely than African-Surinamese men to have hypertension 0.54
      (0.36-0.81). The same pattern applied to the Hindustani-Surinamese, although less
      pronounced 0.59 (0.34-1.02). CONCLUSION: Gender differences in hypertension are
      not consistent across ethnic groups. The lack of differences in ethnic minority
      groups is related to lifestyle factors particularly overweight and obesity.

PMID- 18617884
TI  - New roles for TIM family members in immune regulation.
AB  - Members of the TIM (T-cell immunoglobulin domain and mucin domain) protein family
      are emerging as important regulators of immune responses. As their names imply,
      the TIM proteins were originally thought to be T-cell-specific molecules that
      served mainly to regulate T-helper-cell responses. However, the recent discovery
      that antigen-presenting cells also express TIM molecules and the identification
      of new TIM-protein ligands has expanded the known roles of the TIM proteins in
      immune regulation.

PMID- 18617885
TI  - WNT signalling in the immune system: WNT is spreading its wings.
AB  - WNT proteins are secreted morphogens that are required for basic developmental
      processes, such as cell-fate specification, progenitor-cell proliferation and the
      control of asymmetric cell division, in many different species and organs. In
      blood and immune cells, WNT signalling controls the proliferation of progenitor
      cells and might also affect the cell-fate decisions of stem cells. Recent studies
      indicate that WNT proteins also regulate effector T-cell development, regulatory
      T-cell activation and dendritic-cell maturation. WNT signalling seems to function
      as a universal mechanism in leukocytes to establish a pool of undifferentiated
      cells for further selection, effector-cell maturation and terminal
      differentiation. WNT signalling is therefore subject to strict molecular control,
      and dysregulated WNT signalling is implicated in the development of
      haematological malignancies.

PMID- 18617887
TI  - The adult human brain in preclinical drug development.
AB  - Neurodegenerative disorders are caused by the death and dysfunction of brain
      cells, but despite a huge worldwide effort, no neuroprotective treatments that
      slow cell death currently exist. The failure of translation from animal models to
      humans in the clinic is due to many factors including species differences, human
      brain complexity, age, patient variability and disease-specific phenotypes.
      Additional methods are therefore required to overcome these obstacles in
      neuroprotective drug development. Incorporating target validation using human
      brain-tissue microarray screening and direct human brain-cell testing at an early
      preclinical stage to isolate molecules that protect the human brain may be an
      effective strategy.

PMID- 18617886
TI  - Impact of MHC class I diversity on immune control of immunodeficiency virus
      replication.
AB  - The recent failure of the T-cell-based HIV vaccine trial led by Merck & Co., Inc.
      prompts the urgent need to refocus on the question of which T-cell responses are
      required to control HIV replication. The well-described association between the
      expression of particular MHC class I molecules and successful containment of HIV
      or, in the macaque model, SIV replication provide a valuable starting point from
      which to evaluate more precisely what might constitute effective CD8(+) T-cell
      responses. Here, we review recent studies of T-cell-mediated control of HIV and
      SIV infection, and offer insight for the design of a successful T-cell-based HIV
      vaccine in the future.

PMID- 18617888
TI  - The type VI secretion toolkit.
AB  - Bacterial secretion systems are macromolecular complexes that release virulence
      factors into the medium or translocate them into the target host cell. These
      systems are widespread in bacteria allowing them to infect eukaryotic cells and
      survive or replicate within them. A new secretion system, the type VI secretion
      system (T6SS), was recently described and characterized in several pathogens.
      Genomic data suggest that T6SS exist in most bacteria that come into close
      contact with eukaryotic cells, including plant and animal pathogens. Many
      research groups are now investigating the underlying mechanisms and the way in
      which the effector proteins translocated through this machine subvert host
      defences. This review provides an overview of our current knowledge about type VI
      secretion, focusing on gene regulation, components of the secretion machine,
      substrate secretion and the cellular consequences for the host cell.

PMID- 18617889
TI  - Many forkheads in the road to regulation. Symposium on forkhead transcription
      factor networks in development, signalling and disease.

PMID- 18617890
TI  - The O-linked N-acetylglucosamine modification in cellular signalling and the
      immune system. 'Protein modifications: beyond the usual suspects' review series.
AB  - The intracellular modification of proteins by the addition of a single O-linked N
      acetylglucosamine (O-GlcNAc) molecule is a ubiquitous post-translational
      modification in eukaryotic cells. It is catalysed by O-linked N
      acetylglucosaminyltransferase, which attaches O-GlcNAc to serine/threonine
      residues, and it is counter-regulated by beta-N-acetylglucosaminidase, which is
      the antagonistic glycosidase that removes the O-GlcNAc group. O-GlcNAc
      modification competes with phosphorylation by protein kinases at similar sites,
      thereby affecting important signalling nodes. Accumulating evidence supports a
      central role for O-GlcNAc modifications and the corresponding enzymes in the
      regulation of immune cells, particularly in the activation processes of T and B
      lymphocytes. Here, we discuss recent advances in the field of O-GlcNAc
      modifications, focusing on the cells of the immune system.

PMID- 18617891
TI  - SUMO-modified Sp3 represses transcription by provoking local heterochromatic gene
      silencing.
AB  - Modification of many transcription factors including Sp3 and steroidogenic factor
      1 with the small ubiquitin-like modifier (SUMO) is associated with
      transcriptional repression. Here, we show that SUMOylation of transcription
      factors bound to DNA provokes the establishment of compacted repressive chromatin
      with characteristics of heterochromatin. Chromatin immunoprecipitation
      experiments revealed SUMO-dependent recruitment of the chromatin remodeller Mi-2,
      MBT-domain proteins, heterochromatic protein 1, and the histone
      methyltransferases SETDB1 and SUV4-20H, concomitant with the establishment of
      histone modifications associated with repressed genes, including H3K9 and H4K20
      trimethylation. These results indicate that SUMOylation has a crucial role in
      regulating gene expression by initiating chromatin structure changes that render
      DNA inaccessible to the transcription machinery.

PMID- 18617892
TI  - SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100
      phosphorylation and processing.
AB  - A primary step in activating the alternative nuclear factor-kappaB (NF-kappaB)
      pathway requires NF-kappaB2/p100 processing to generate p52. In most cases,
      stimuli-induced p100 processing is dependent on NF-kappaB-inducing kinase/IkappaB
      kinase alpha-mediated phosphorylation and ubiquitination. Here, we report that
      post-translational modification of p100 at specific sites by the small ubiquitin
      like modifier (SUMO) is another determining factor for stimuli-induced p100
      processing. The results show that basal SUMO modification is required for stimuli
      induced p100 phosphorylation and that blocking SUMOylation of p100, either by
      site-directed mutation or by short interfering RNA-targeted diminution of E2 SUMO
      conjugating enzyme Ubc9, inhibits various physiological stimuli-induced p100
      processing and ultimate activation of the alternative NF-kappaB pathway.
      Together, these findings show the crucial role of SUMO1 modification in p100
      processing and provide mechanistic insights into the participation of SUMO1
      modification in the regulation of signal transduction.

PMID- 18617893
TI  - Dynamic states of the DNA repair enzyme AlkB regulate product release.
AB  - The 2-oxoglutarate (2OG)- and Fe(2+)-dependent dioxygenase AlkB couples the
      demethylation of modified DNA to the decarboxylation of 2OG. Extensive
      crystallographic analyses have shown no evidence of significant structural
      differences between complexes binding either 2OG or succinate. By using nuclear
      magnetic resonance spectroscopy, we have shown that the AlkB-succinate and AlkB
      2OG complexes have significantly different dynamic properties in solution. 2OG
      makes the necessary contacts between the metal site and the large beta-sheet to
      maintain a fully folded conformation. Oxidative decarboxylation of 2OG to
      succinate leads to weakening of a main contact with the large beta-sheet,
      resulting in an enhanced dynamic state. These conformational fluctuations allow
      for the replacement of succinate in the central core of the protein and probably
      contribute to the effective release of unmethylated DNA. We also propose that the
      inherent dynamics of the co-product complex and the subsequent increased
      molecular ordering of the co-substrate complex have a role in DNA damage
      recognition.

PMID- 18617894
TI  - Focal degeneration of astrocytes in amyotrophic lateral sclerosis.
AB  - Astrocytes emerge as key players in motor neuron degeneration in Amyotrophic
      Lateral Sclerosis (ALS). Whether astrocytes cause direct damage by releasing
      toxic factors or contribute indirectly through the loss of physiological
      functions is unclear. Here we identify in the hSOD1(G93A) transgenic mouse model
      of ALS a degenerative process of the astrocytes, restricted to those directly
      surrounding spinal motor neurons. This phenomenon manifests with an early onset
      and becomes significant concomitant with the loss of motor cells and the
      appearance of clinical symptoms. Contrary to wild-type astrocytes, mutant hSOD1
      expressing astrocytes are highly vulnerable to glutamate and undergo cell death
      mediated by the metabotropic type-5 receptor (mGluR5). Blocking mGluR5 in vivo
      slows down astrocytic degeneration, delays the onset of the disease and slightly
      extends survival in hSOD1(G93A) transgenic mice. We propose that excitotoxicity
      in ALS affects both motor neurons and astrocytes, favouring their local
      interactive degeneration. This new mechanistic hypothesis has implications for
      therapeutic interventions.

PMID- 18617895
TI  - Yes-associated protein (YAP) functions as a tumor suppressor in breast.
AB  - Yes-associated protein (YAP) has been shown to positively regulate p53 family
      members and to be negatively regulated by the AKT proto-oncogene product in
      promoting apoptosis. On the basis of this function and its location at 11q22.2, a
      site of frequent loss of heterozygosity (LOH) in breast cancer, we investigated
      whether YAP is a tumor suppressor in breast. Examination of tumors by
      immunohistochemistry demonstrated significant loss of YAP protein. LOH analysis
      revealed that protein loss correlates with specific deletion of the YAP gene
      locus. Functionally, short hairpin RNA knockdown of YAP in breast cell lines
      suppressed anoikis, increased migration and invasiveness, inhibited the response
      to taxol and enhanced tumor growth in nude mice. This is the first report
      indicating YAP as a tumor suppressor, revealing its decreased expression in
      breast cancer as well as demonstrating the functional implications of YAP loss in
      several aspects of cancer signaling.

PMID- 18617896
TI  - The Bcr-Abl kinase inhibitor INNO-406 induces autophagy and different modes of
      cell death execution in Bcr-Abl-positive leukemias.
AB  - Bcr-Abl tyrosine kinase (TK) inhibitors are promising therapeutic agents for Bcr
      Abl-positive (Bcr-Abl(+)) leukemias. Although they are known to promote caspase
      mediated apoptosis, it remains unclear whether caspase-independent cell death
      inducing mechanisms are also triggered. Here we demonstrated that INNO-406, a
      second-generation Bcr-Abl TK inhibitor, induces programmed cell death (PCD) in
      chronic myelogenous leukemia (CML) cell lines through both caspase-mediated and
      caspase-independent pathways. The latter pathways include caspase-independent
      apoptosis (CIA) and necrosis-like cell death (CIND), and the cell lines varied
      regarding which mechanism was elicited upon INNO-406 treatment. We also observed
      that the propensity toward CIA or CIND in cells was strongly associated with
      cellular dependency on apoptosome-mediated caspase activity. Cells that undergo
      CIND have a high apoptosome activity potential whereas cells that undergo CIA
      tend to have a lower potential. Moreover, we found that INNO-406 promotes
      autophagy. When autophagy was inhibited with chloroquine or gene knockdown of
      beclin1 by shRNA, INNO-406-induced cell death was enhanced, which indicates that
      the autophagic response of the tumor cells is protective. These findings suggest
      new insights into the biology and therapy of Bcr-Abl(+) leukemias.

PMID- 18617897
TI  - Zinc chelation induces rapid depletion of the X-linked inhibitor of apoptosis and
      sensitizes prostate cancer cells to TRAIL-mediated apoptosis.
AB  - The X-linked inhibitor of apoptosis (XIAP), the most potent member of the
      inhibitor of apoptosis protein (IAP) family of endogenous caspase inhibitors,
      blocks the initiation and execution phases of the apoptotic cascade. As such,
      XIAP represents an attractive target for treating apoptosis-resistant forms of
      cancer. Here, we demonstrate that treatment with the membrane-permeable zinc
      chelator, N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces a
      rapid depletion of XIAP at the post-translational level in human PC-3 prostate
      cancer cells and several non-prostate cell lines. The depletion of XIAP is
      selective, as TPEN has no effect on the expression of other zinc-binding members
      of the IAP family, including cIAP1, cIAP2 and survivin. The downregulation of
      XIAP in TPEN-treated cells occurs via proteasome- and caspase-independent
      mechanisms and is completely prevented by the serine protease inhibitor,
      Pefabloc. Finally, our studies demonstrate that TPEN promotes activation of
      caspases-3 and -9 and sensitizes PC-3 prostate cancer cells to TRAIL-mediated
      apoptosis. Taken together, our findings indicate that zinc-chelating agents may
      be used to sensitize malignant cells to established cytotoxic agents via
      downregulation of XIAP.

PMID- 18617898
TI  - Exosome secretion, including the DNA damage-induced p53-dependent secretory
      pathway, is severely compromised in TSAP6/Steap3-null mice.
AB  - TSAP6 (tumor suppressor-activated pathway 6), also known as Steap3, is a direct
      p53 transcriptional target gene. It regulates protein secretion, for example
      translationally controlled tumor protein (TCTP), which is implicated in tumor
      reversion. In keeping with the latter, we show herein that TSAP6 is a
      glycosylated protein present in the trans-Golgi network, endosomal-vesicular
      compartment and cytoplasmic membrane. To further investigate the physiological
      function of TSAP6, we have generated TSAP6-deficient mice. These mice exhibit
      microcytic anemia with abnormal reticulocyte maturation and deficient transferrin
      receptor downregulation, a process known to be dependent on exosomal secretion.
      Moreover, we provide direct evidence that exosome production is severely
      compromised in TSAP6-null cells. Finally, we show that the DNA damage-induced p53
      dependent nonclassical exosomal secretory pathway is abrogated in TSAP6-null
      cells. Given the fact that exosomes are used as cell-free vaccines against cancer
      and that they could be involved in the biogenesis and spread of human
      immunodeficiency virus, it is important to understand their regulation. The
      results presented here provide the first genetic demonstration that exosome
      formation is a tightly controlled biological process dependent of TSAP6.

PMID- 18617899
TI  - Autophagic disposal of the aggregation-prone protein that causes liver
      inflammation and carcinogenesis in alpha-1-antitrypsin deficiency.
AB  - Alpha-1-antitrypsin (AT) deficiency is a relatively common autosomal co-dominant
      disorder, which causes chronic lung and liver disease. A point mutation renders
      aggregation-prone properties on a hepatic secretory protein in such a way that
      the mutant protein is retained in the endoplasmic reticulum of hepatocytes rather
      than secreted into the blood and body fluids where it ordinarily functions as an
      inhibitor of neutrophil proteases. A loss-of-function mechanism allows neutrophil
      proteases to degrade the connective tissue matrix of the lung causing chronic
      emphysema. Accumulation of aggregated mutant AT in the endoplasmic reticulum of
      hepatocytes causes liver inflammation and carcinogenesis by a gain-of-toxic
      function mechanism. However, genetic epidemiology studies indicate that many, if
      not the majority of, affected homozygotes are protected from liver disease by
      unlinked genetic and/or environmental modifiers. Studies performed over the last
      several years have demonstrated the importance of autophagy in disposal of
      mutant, aggregated AT and raise the possibility that predisposition to, or
      protection from, liver injury and carcinogenesis is determined by the balance of
      de novo biogenesis of the mutant AT molecule and its autophagic disposal.

PMID- 18617900
TI  - Spatial differences in active caspase-8 defines its role in T-cell activation
      versus cell death.
AB  - Caspase-8, a cysteine-protease, initiates apoptosis when activated by death
      receptors. Caspase-8 is also essential for initiating T lymphocyte proliferation
      following T-cell antigen receptor (TCR) signaling. Given these disparate
      functions of caspase-8, we sought to determine whether this represented only a
      difference in the magnitude of caspase-8 activation, or different intracellular
      locations of active caspase-8. We demonstrate by high-resolution multicolor
      confocal laser scanning microscopy an aggregation of active caspase-8 within
      membrane lipid rafts in T cells stimulated with anti-CD3. This suggests that
      following TCR stimulation active caspase-8 physically interacts with lipid raft
      proteins, possibly to form a signaling platform. In contrast, Fas stimulation of
      T cells resulted in a much more profound activation of caspase-8 that was
      exclusively cytosolic. These confocal microscopic findings were confirmed using
      discontinuous sucrose gradient ultracentrifugation to isolate lipid raft versus
      cytosolic components. This sequestration model of caspase-8 activation was
      further supported by the observation that a classic caspase-8 substrate, BID, was
      not cleaved in CD3-stimulated T cells, but was cleaved after Fas engagement. Our
      data support a model that the location of active caspase-8 may profoundly
      influence its functional capacity as a regulator of either cell cycling or cell
      death.

PMID- 18617901
TI  - A novel mutation in CRYBB2 responsible for inherited coronary cataract.
AB  - PURPOSE: To study the molecular pathogenesis of a Chinese family with coronary
      form of cataract. METHODS: One Chinese three-generation family with inherited
      coronary cataract phenotype was recruited. Five affected and seven unaffected
      family members attended our study. Genome-wide linkage analysis was applied to
      map the disease loci, and two candidate genes from a locus on chromosome 1 and a
      locus on chromosome 22 were sequenced for mutation identification. Software at
      the Expasy proteomics server was utilized to predict the mutation effect on
      proteins. RESULTS: Whole genome linkage analysis indicated some regions on
      chromosome 1, 10, and 22, with LOD score values greater than 1. Within these
      loci, the GJA8 and CRYBB2 genes, located in the two loci with the highest LOD
      score of 1.51 on chromosomes 1 and 22, respectively, were sequenced. A novel
      mutation c.92C>G in exon 2 of CRYBB2 causing S31W was identified in all five
      patients. It was not found in 95 unrelated controls. This missense sequence
      alteration likely enhanced the local solubility. Around the mutation site, a
      lipocalin signature motif was predicted by ScanProsite. CONCLUSIONS: A novel
      disease-causing mutation S31W in CRYBB2 was identified in a Chinese cataract
      family. It is the first reported mutation for coronary cataract. Functional
      characterization should be carried out to evaluate the biological effects of this
      mutant.

PMID- 18617902
TI  - Incidence and clinical characteristics in a Colombian cohort of ocular
      toxoplasmosis.
AB  - PURPOSE: To evaluate the incidence and clinical features of patients with ocular
      toxoplasmosis in a Colombian cohort. METHODS: We collected prospectively the
      clinical features of patients with ocular toxoplasmosis seen at the 'Universidad
      del Quindio' health centre between September 2005 and September 2007 (24 months).
      RESULTS: Seventy patients were included in the analysis (95 affected eyes). The
      median age at the first episode was 21 years (range: 1-54 years). Thirty-two
      patients had active lesions (45.7%), one of them had active lesions in both eyes.
      The acquisition of infection was determined in 14 patients as congenital (20%),
      in seven as an acquired postnatal infection (10%), and in 49 as undetermined
      (70%). Bilateral involvement was found in 25 cases (35.7%). Unilateral legal
      blindness (<20/200) was found in 14 of 37 inactive cases (37.8%). The most
      frequent complication was strabismus (n: 12; 13.4%). CONCLUSIONS: There is a high
      incidence of cases of ocular toxoplasmosis in Quindio region (three new episodes
      by 100,000 inhabitants by year). Clinical features of ocular toxoplasmosis in
      Colombia are similar to those reported in other regions but there are no
      comparative data about the size and number of lesions.

PMID- 18617903
TI  - Exposure to verteporfin and bevacizumab therapy for choroidal neovascularization
      secondary to punctate inner choroidopathy during pregnancy.

PMID- 18617904
TI  - Posterior scleritis presenting with simultaneous branch retinal artery occlusion
      and exudative retinal detachment.

PMID- 18617905
TI  - Transmission electron microscopy of the rabbit posterior capsule irrigated with
      thapsigargin and 5-fluorouracil in a sealed-capsule irrigation device.
AB  - PURPOSE: To investigate, by transmission electron microscopy (TEM), the effect on
      the posterior capsule of a young rabbit eye of 5-fluorouracil (5-FU) or
      thapsigargin in a sealed-capsule irrigation device. SETTING: St Erik's Eye
      Hospital, Stockholm, Sweden. METHODS: Clear lens extraction was performed
      unilaterally in eight 4-week-old rabbits. A sealed-capsule irrigation device was
      irrigated for 2 min with 20 ml of one of the following: balanced salt solution
      (BSS; n=2), thapsigargin 300 muM (n=2), 5-FU 50 mg/ml (n=2), or 5-FU 25 mg/ml
      (n=2). The substances were washed out for 10 s with BSS. The eyes were left
      aphakic. Six weeks postoperatively, the animals were killed, and the posterior
      capsule was extracted and fixed for TEM. As a control, we also evaluated the
      capsules from the two fellow eyes in the BSS group that did not undergo surgery.
      RESULTS: The ultrastructure of the posterior capsule in eyes irrigated with 5-FU
      or thapsigargin did not differ from that in the eyes irrigated with BSS or in the
      eyes that did not have surgery. The membranes had the same ultrastructure with
      thin collagen fibres on the anterior and posterior face of the posterior capsule
      and an amorphic matrix. CONCLUSION: Thapsigargin or 5-FU used in a sealed-capsule
      irrigation device does not seem to harm the posterior capsule, which appeared
      similar to when the capsule is irrigated with BSS.

PMID- 18617906
TI  - Fat-forming variant of solitary fibrous tumour of the orbit: the entity
      previously known as lipomatous haemangiopericytoma.

PMID- 18617907
TI  - Cross-infection risk of felt-tipped marker pens in cataract surgery.
AB  - PURPOSE: To assess the potential of bacterial transmission using felt-tipped
      marker pens on forehead skin before cataract surgery. METHODS: A total of 64
      marker pens taken from clinical stock were tested. Forty-eight new pens were
      cultured in the laboratory. They were first left to desiccate for 0, 4, and 16 h,
      then dipped into solutions of 0.5 Macfarlane's concentration of coagulase
      negative staphylococci (CNS), methicillin-resistant Staphylococcus aureus (MRSA)
      and coliforms, and transferred onto the culture medium after 5, 10, 30, and 120
      min intervals of exposure to air. A further 16 pens were collected after routine
      clinical use for 5 working days and cultured. RESULTS: Positive cultures were
      observed in 100% of pens at 0 min, and 44.4% at 5 min after the organism was
      exposed to air. Escherichia coli showed least transmissibility with no growth in
      all plates after 5 min of exposure. Only MRSA showed heavy growth after 10 min of
      exposure. No pattern emerged with reference to the length of time; each pen was
      left to desiccate. No growth was observed in the cultures of all 16 marking pens
      after clinical use. CONCLUSIONS: The potential for transmission of bacteria
      through felt-tipped marker pens has not been explored in cataract surgery. This
      study demonstrated that a theoretical risk of transmission exists in a laboratory
      setting, and survival times of the bacteria decreased with time. This suggests
      that the interval in which patients are marked with the same pen may play a role
      in bacterial transmission.

PMID- 18617908
TI  - Persistency with medical treatment for glaucoma and ocular hypertension in the
      United Kingdom: 1994-2005.
AB  - PURPOSE: To examine trends and demographic factors affecting persistence with
      ocular hypotensive therapy, from a period before prostaglandins were available to
      when they were the most common therapy. METHODS: Computerised patient records
      from 94 general practices across the United Kingdom, identified 5670 registered
      patients newly prescribed an ocular hypotensive drug (1993-2005). Persistence was
      defined as continuing therapy without a 90-day gap in prescription for (i) any
      ocular hypotensive and (ii) initial monotherapy. Time to failure with the
      treatment was compared using proportional hazard analyses, adjusted for age,
      gender, practice, year of initial treatment, and a sociodemographic indicator.
      Study findings were set in the context of a review of the literature. RESULTS:
      Percentage persistent at 1-year rose after 1997 when prostaglandins were
      introduced; from 61% in 1994-1996 to 70% in 2002-2004. Persistence with any
      treatment did not differ between those initiated on beta-blockers compared to
      prostaglandins (1.05, 95% CI 0.93-1.17). However, 20% of subjects initiated on
      beta-blockers received a prostaglandin by 1 year. Conversely, 8% of those
      initiated on prostaglandins received a beta-blocker. When failure with initial
      therapy was considered, beta-blockers appeared worse (1.35, 95% CI 1.21-1.50);
      this was consistent with findings from six studies in the review (1.40, 95% CI
      1.34-1.46). Neither gender nor social factors were associated with persistence,
      but younger subjects (35-64 years) were significantly more likely to fail as were
      those over 85 years. CONCLUSIONS: Introduction of prostaglandins may explain an
      improvement in persistence over a decade. However, whether the higher cost of
      initiating patients on prostaglandins is justified remains questionable unless
      clinically indicated.

PMID- 18617909
TI  - The prevalence of patients with ocular genetic disorders attending a general
      paediatric ophthalmology clinic in the East End of London.
AB  - AIMS: To document the prevalence of ocular genetic disorders in a general
      paediatric ophthalmology clinic in a deprived, ethnically diverse inner city area
      of London, and to assess the consanguineous relationships and ethnicity among
      families with these conditions. METHODS: A prospective audit documented all
      ocular genetic conditions (excluding strabismus and amblyopia) presenting for 16
      consecutive weeks to the paediatric ophthalmology clinic. Information regarding
      ethnicity and consanguinity were sought. The disorders were divided according to
      the mode of inheritance if known. RESULTS: Thirteen per cent of patients (45/342)
      had an ocular genetic disorder or were being examined for one. Of them, 22%
      (10/45) had a history of consanguinity with an inheritance pattern of 30%
      autosomal recessive (3/10), 20% autosomal dominant, 50% X-linked/unknown/isolated
      cases. In the remaining non-consanguineous families (35/45), 22% were autosomal
      recessive, 17% autosomal dominant, and 60% X-linked/unknown/isolated cases. The
      vast majority of cases (9/10) with a history of consanguineous marriage had South
      Asian ancestry. Variable ethnic backgrounds were documented for patients with
      genetic disease and no consanguinity. CONCLUSION: Ocular genetic disorders are
      common in secondary care. Less than a third of patients with such disorders had a
      family history of consanguinity. The proportion of patients with proven autosomal
      recessive disease was similar irrespective of consanguinity within family. The
      proportion of children of South Asian ancestry was high in this clinic
      population.

PMID- 18617910
TI  - Iris naevus with recurrent spontaneous hyphema simulating an iris melanoma.

PMID- 18617911
TI  - Measurement of fornix depth and area: a novel method of determining the severity
      of fornix shortening.
AB  - PURPOSE: To measure the depth and area of the fornix in normal adults and
      patients with symblepharon. METHODS: The fornix depth of normal eyes (n=20) and
      patients with symblepharon (Stevens-Johnson syndrome, n=4) was measured at six
      locations in each eye using non-invasive, dull-edged stainless steel metric
      scale. Before and after conjunctival reconstruction surgery, the depths of fornix
      were also measured by the same method. The overall area was assessed from those
      fornix depth at six points. RESULTS: The mean depths of the superior nasal and
      temporal, inferior nasal and temporal, fornices as well as mean depths of medial
      nasal and temporal canthi fornices in normal eyes were 14.1+/-2.5, 14.1+/-2.5,
      10.0+/-2.1, 10.4+/-1.8, 3.0+/-0.9, and 5.2+/-1.2 mm, respectively. The mean
      overall area of the conjunctival fornix in normal subjects was 909.6+/-162.2
      mm(2). All these parameters were significantly lower in the eyes of patients.
      Both depth and area after surgery were significantly deeper and larger than
      before. CONCLUSIONS: This estimation may prove useful when evaluating the
      severity of symblepharon and determining the post-surgical prognosis.

PMID- 18617912
TI  - Transient amaurosis with intracameral lidocaine.

PMID- 18617913
TI  - Trends in rates of trabeculectomy in England.
AB  - AIMS: Rates of glaucoma surgery have declined in North America and continental
      Europe in recent years. The aim of this study was to examine trends over time and
      regional variation in rates of trabeculectomy in England. METHODS: The hospital
      in-patient enquiry (HIPE), hospital episode statistics (HES), and the Oxford
      record linkage study (ORLS) were analysed for annual trabeculectomy admissions
      between 1976 and 2004. RESULTS: Annual rates of admission for trabeculectomy rose
      10-fold from 1976 to 1995: from 3.7 (95% confidence intervals 3.5-3.9) admissions
      per 100,000 population in 1976 to a peak of 38.7 (38.1-39.3) in 1995. Admission
      rates then declined sharply and have begun to reach a plateau at around 10.6
      (10.3-10.9) in 2004. The highest surgical rates during the period 1997-2004 were
      found in the 80- to 84-year-old age group. Geographical analysis showed wide
      variation across local authority areas in annual rates of trabeculectomy, from 4
      (2.3-5.2) to 33 (29.0-36.5) people per 100,000 population in 1998-2004. The rate
      of surgery by local authority showed little or no association with the level of
      social deprivation in each area. CONCLUSIONS: The rate of patients undergoing
      trabeculectomy increased substantially over 20 years. This was followed by a
      profound reduction in rates of trabeculectomy from 1995, which coincides with the
      introduction of new topical medications to reduce intraocular pressure. Wide
      regional variation in rates of trabulectomy was found, but there was no evidence
      of reduced access to glaucoma surgery in deprived areas.

PMID- 18617914
TI  - Conditioned medium from Ad-IFN-alpha-infected bladder cancer and normal
      urothelial cells is cytotoxic to cancer cells but not normal cells: further
      evidence for a strong bystander effect.
AB  - We have reported earlier that a bystander effect is seen in cancer cells that are
      resistant to high concentrations of the interferon-alpha protein (Intron A) when
      treated with adenoviral-mediated interferon-alpha (Ad-IFN-alpha). We now provide
      further evidence for this bystander effect using conditioned medium (CM)
      collected from Ad-IFN-alpha-infected cancer and normal urothelial cells. The CMs
      collected from UC-9 and KU7 bladder cancer cells as well as normal urothelial
      cells following transfection with Ad-IFN produce cell death when added to various
      cancer cell types in culture but not to normal urothelial cells. The CM could be
      filtered, frozen and thawed, and diluted to at least one part Ad-IFN CM to five
      parts fresh control medium and the diluted CM still shows a similar cytotoxicity
      as a 100% concentration of Ad-IFN CM. This cytotoxicity was observed by both flow
      cytometry and MTT assays as well as by phase microscopy, and a significant sub-G1
      population was seen whether the CM was collected 48, 72 or 96 h after initial Ad
      IFN treatment. In addition, the CM could be partially inactivated by exposure to
      65 degrees C for 30 min and totally inactivated by placement at 92 degrees C for
      3 min, whereas Intron A was not inactivated under the same conditions.
      Importantly, although significant caspase 8 and caspase 9 cleavage occurred in Ad
      IFN-treated cells as a direct effect of Ad-IFN transfection, the Ad-IFN CM
      produced no activation of caspase 8 and caspase 9, indicating that a different
      mechanism of cell death was produced by the bystander factor(s) than the direct
      effect of Ad-IFN. This bystander effect in turn may play an important role in the
      efficacy of the current Ad-IFN clinical trial for superficial bladder cancer now
      underway.

PMID- 18617916
TI  - Intratumoral gene delivery of anti-cathepsin L single-chain variable fragment by
      lentiviral vector inhibits tumor progression induced by human melanoma cells.
AB  - We previously demonstrated that the switch from non- to highly tumorigenic
      phenotype of human melanoma cells is directly related to procathepsin L
      secretion, which increased cell resistance to complement-mediated cell lysis.
      Involvement of procathepsin L secretion in tumor growth was clearly demonstrated
      by three different strategies: (1) inhibition of secreted procathepsin L
      activity; (2) increase of procathepsin L secretion; and (3) inhibition of
      procathepsin L secretion. This latter strategy was triggered by intracellular
      expression of anti-human cathepsin L single-chain variable fragment (ScFv). These
      previous experiments were performed by processing melanoma cells before their
      injection into nude mice. We herein designed a new lentiviral vector in which
      this anti-cathepsin L ScFv was cloned. This lentiviral vector was optimized to
      allow the highest intracellular expression of anti-cathepsin L ScFv in transduced
      melanoma cells. In these transduced cells, procathepsin L secretion was strongly
      inhibited. In addition, injection of this anti-cathepsin L ScFv lentiviral vector
      into tumors already induced in nude mice inhibited tumor growth and associated
      angiogenesis. This is the first report to demonstrate that targeting procathepsin
      L secretion with anti-cathepsin L ScFv lentiviral construct constitutes a new
      gene therapy in the challenge to inhibit the growth of tumors induced by human
      melanoma cells.

PMID- 18617915
TI  - Adenovirus-mediated HCCS1 overexpression elicits a potent antitumor efficacy on
      human colorectal cancer and hepatoma cells both in vitro and in vivo.
AB  - We had characterized earlier the novel tumor suppressor gene hepatocellular
      carcinoma suppressor 1 (HCCS1), and demonstrated that expression of exogenous
      HCCS1 gene in human hepatocarcinoma cells could remarkably suppress their
      abilities to develop tumors in nude mice and to form colonies in soft agar. In
      this study, we provide further experimental evidence to confirm the role of HCCS1
      as a tumor suppressor gene and investigate its potential in therapeutic
      applications by using adenovirus vectors. We show that HCCS1 overexpression,
      mediated by replication-deficient adenovirus, significantly suppressed the growth
      of human colorectal cancer cells, as well as hepatocellular carcinoma cells in
      vitro and in vivo. To further improve its antitumor efficacy, we inserted the
      HCCS1 gene into an oncolytic adenovirus. This HCCS1-armed oncolytic adenovirus
      exhibited a dramatic inhibitory effect on cancer cells in vitro and in vivo, and
      led to a complete regression of 50% of established tumor xenografts in nude mice.
      Taken together, our data suggest that HCCS1 is a promising therapeutic gene for
      the treatment of human cancers.

PMID- 18617917
TI  - Polyethylenimine-mediated in vivo gene transfer of a transmembrane superantigen
      fusion construct inhibits B16 murine melanoma growth.
AB  - Immunotherapy has been proposed as a therapeutic strategy in advanced-stage
      melanomas in which other therapeutic options have little effect. The
      Staphylococcus enterotoxin A (SEA) has been used to stimulate an antitumoral
      immune response but its use is hampered by severe systemic side effects. Here, we
      show that SEA can be targeted to melanoma cells to limit these side effects. More
      specifically, we used a nonviral vector, the cationic polymer, polyethylenimine
      (PEI), to express a transmembrane SEA fusion construct (pSEA-TM) in B16F10
      induced subcutaneous melanoma in mice. The efficacy of this in vivo transfection
      was enhanced by concomitant infusion of epinephrine to induce local
      vasoconstriction. In these conditions, repeated injections of pSEA-TM/PEI
      complexes elicited a significant response, as evidenced by tumor growth
      inhibition, without systemic adverse effects. T cell infiltration of the tumors,
      together with positive lymphocyte proliferation tests, suggested local and
      systemic immune responses. Altogether, PEI-mediated targeting of SEA to melanoma
      tumor cells in vivo efficiently stimulates the antitumor immune response without
      inducing the side effects observed with systemic administration of SEA.

PMID- 18617918
TI  - Bench marks.

PMID- 18617919
TI  - Overseas registration.

PMID- 18617920
TI  - Confirm the efficacy.

PMID- 18617921
TI  - Unusual fusion.

PMID- 18617922
TI  - Socio-dental measure.

PMID- 18617923
TI  - Unnecessary waste.

PMID- 18617925
TI  - Gag technique.

PMID- 18617924
TI  - Medical and dental gold.

PMID- 18617926
TI  - New contract failing to improve dental services say MPs, as health committee
      urges review of UDAs.

PMID- 18617930
TI  - UK's smallest dental school tops Times university guide.

PMID- 18617929
TI  - Royal College of Surgeons launches appeal to save Great War drawings.

PMID- 18617935
TI  - Access to special care dentistry, part 2. Communication.
AB  - This article considers what communication is, its elements, what helps and what
      hinders it, and why it matters. It also considers managing people with
      communication differences and when communication is affected in special care
      dentistry (SCD). The article focuses on patients with hearing and visual
      impairments and considers how communication is affected and what techniques can
      be used to improve the situation. It offers recommendations for communicating
      with patients with neurological impairments typically seen after stroke, such as
      aphasia and dysarthria, with tips for the listener including the use of
      communication aids where appropriate. Finally it will consider communicating with
      patients who have autistic spectrum conditions and discuss how effective
      techniques and a tailored approach to their specific needs and anxieties can
      increase the likelihood of a successful dental visit.

PMID- 18617936
TI  - Case report: foreign body in the palate of an infant.
AB  - Most foreign body aspirations occur in children younger than five years old, with
      65% of deaths affecting infants younger than one year. A reasonably uncommon
      eventuality is attachment and retention of the foreign body to the oral mucosal
      tissues and in particular to the soft tissues of the hard palate. The following
      report discusses the unusual presentation of a foreign body in the palate of a
      child as well as the treatment carried out to facilitate the removal of the
      object. This report aims to highlight the importance of considering an impacted
      foreign body in the differential diagnosis of a palatal mass in an infant.

PMID- 18617943
TI  - Making a mark--taking assessment to technology.
AB  - During any course of study, students are assessed usually through a range of
      methods which may include written examinations, coursework assignments,
      professional practice, oral tests and practical examinations. This article
      considers the various forms of assessment in dental education and how information
      and communication technology is being applied to them. As innovative teaching and
      learning methods such as computer simulations are introduced, the assessment of
      results, successes and failures is taking on new forms in many traditional
      courses. The web is also spreading its tentacles into assessment, with the
      benefits of offering almost instant feedback and support. However, technology
      brings its own problems, not least by making ever more ingenious methods of
      plagiarism easier. Educational establishments, therefore, must be aware of such
      problems and have policies in place to counteract them.

PMID- 18617944
TI  - The GDC--lifting the lid. Part 3: education, CPD and revalidation.
AB  - This third article in the series looks at the areas of education, continuing
      professional development and the forthcoming introduction of revalidation, which
      form a 'continuum of quality assurance' through a dentist's professional life and
      ensure that standards of dentistry remain high. The article introduces some of
      the key members of staff involved with education at the General Dental Council
      and details some of the complicated issues involved with regulating dental
      education from undergraduate level onwards.

PMID- 18617969
TI  - Specklegram in a grapefruit fiber and its response to external mechanical
      disturbance in a single-multiple-single mode fiber structure.
AB  - Specklegram in multimode fiber has successfully been used as a sensor for
      detecting mechanical disturbance. Speckles in a multimode pure silica grapefruit
      fiber are observed and compared to that of a step-index multimode fiber, showing
      different features between them. The sensitivities to external disturbance of two
      kinds of fiber were measured, based on single-multiple-single mode (SMS) fiber
      structure. Experimental results show that the grapefruit fiber shows higher
      sensitivity than does the step-index multimode fiber. The transmission spectrum
      of the grapefruit fiber was measured as well, showing some oscillation features
      that are significantly different from that of a step-index multimode fiber. The
      experiments may provide suggestions to understand the mechanisms of light
      propagation in grapefruit fibers.

PMID- 18617970
TI  - Low-threshold cavitation in water using IR laser pulse trains.
AB  - The low-temperature cavitational disruption by trains of laser pulses was
      demonstrated in water. The trains used in the experiment were generated by a
      Raman laser at a wavelength of 1626 nm. The mean value of the fragmentation
      threshold energy density per pulse in a train was estimated to be equal to
      7.2x10(6) J/m(3). The corresponding amplitude of the negative pressure had the
      order of 6-7 bars at a temperature jump of only about 2 degrees C. This result
      opens up prospects for developing precision nonthermal cavitational laser
      surgery.

PMID- 18617971
TI  - Design and parallel fabrication of wire-grid polarization arrays for polarization
      resolved imaging at 1.55 microm.
AB  - Polarization-resolved imaging can provide information about the composition and
      topography of the environment that is invisible to the eye. We demonstrate a
      practical method to fabricate arrays of small, orthogonal wire-grid polarizers
      (WGPs) that can be matched to individual detector pixels, and we present design
      curves that relate the structure to the polarization extinction ratio obtained.
      The photonic area lithographically mapped (PALM) method uses multiple-exposure
      conventional and holographic lithography to create subwavelength patterns easily
      aligned to conventional mask features. WGPs with polarization extinction ratios
      of approximately 10 at a 1.55 microm wavelength were fabricated, and square
      centimeter areas of square micrometer size WGP arrays suitable for polarization
      resolved imaging on glass were realized.

PMID- 18617972
TI  - Pointwise fiber Bragg grating displacement sensor system for dynamic
      measurements.
AB  - A method for setting up a fiber Bragg grating (FBG) sensor which can measure the
      pointwise, out-of-plane or in-plane dynamic displacement is proposed. The
      proposed FBG sensor is reusable. A multiplexing demodulation system based on a
      single long-period fiber grating is used in this study. The experimental results
      of the steady-state motion for a multilayer piezoelectric actuator and the
      dynamic response of a cantilever beam subjected to impact loadings are presented.
      These results indicate that the proposed displacement sensor has the ability to
      measure the out-of-plane dynamic displacement with high sensitivity. Measurements
      for a piezoceramic plate excited by high frequency show that the proposed
      displacement sensor also has the ability to provide the in-plane dynamic
      displacement up to 20 kHz.

PMID- 18617973
TI  - Temporal response of surface-relief fiber Bragg gratings to high temperature CO2
      laser heating.
AB  - The authors use a fiber sensor integrated monitor (FSIM) as a fully functioning
      system to characterize the temporal response of a surface-relief fiber Bragg
      grating (SR-FBG) to temperature heating above 1000 degrees C. The SR-FBG is shown
      to have a rise time of about 77 ms for heating and a fall time of about 143 ms
      for cooling. The FSIM also provides full spectral scans at high speed that can be
      used to gain further insights into the temperature dynamics of a given system.

PMID- 18617974
TI  - Unsupervised illuminant estimation from natural scenes: an RGB digital camera
      suffices.
AB  - A linear pseudo-inverse method for unsupervised illuminant recovery from natural
      scenes is presented. The algorithm, which uses a digital RGB camera, selects the
      naturally occurring bright areas (not necessarily the white ones) in natural
      images and converts the RGB digital counts directly into the spectral power
      distribution of the illuminants using a learning-based spectral procedure.
      Computations show a good spectral and colorimetric performance when only three
      sensors (a three-band RGB camera) are used. These results go against previous
      findings concerning the recovery of spectral reflectances and radiances, which
      claimed that the greater the number of sensors, the better the spectral
      performance. Combining the device with the appropriate computations can yield
      spectral information about objects and illuminants simultaneously, avoiding the
      need for spectroradiometric measurements. The method works well and needs neither
      a white reference located in the natural scene nor direct measurements of the
      spectral power distribution of the light.

PMID- 18617975
TI  - Adaptive disturbance rejection in an optical trap.
AB  - This article presents a method for characterizing the system dynamics of a
      trapped particle in real-time and designing a controller to minimize disturbances
      to the particle's position. Specifically, adaptive system identification is used
      to determine the trap characteristics and the actuator transfer function
      describing the mirror voltage to trap position path. Using an internal model
      control scheme combined with a filtered-x least-mean-square algorithm, adaptive
      control was used to create a controller that minimizes a frequency weighted mean
      squared-error. The dynamics associated with multiple particle sizes and materials
      were experimentally determined under different power levels, each case resulting
      in different system dynamics and demonstrating positive control results. The
      adaptive system identification and the controller presented automate the process
      of system identification and control design, enabling the automation of optical
      trap controller design.

PMID- 18617976
TI  - Shape connection by pattern recognition and laser metrology.
AB  - Shape connection based on the pattern recognition of three-dimensional shapes is
      presented. In this technique, the object shape is reconstructed by laser scanning
      and image processing. The object is reconstructed from multiple views when an
      object occlusion appears. From this process, multiple parts of the object are
      reconstructed. Then, these parts are assembled to obtain the complete object
      shape. To perform the assembling, a matching procedure is applied to a transverse
      section of the multiple views by Hu moments. The depth of the transverse section
      is computed by an approximation network based on the behavior of the laser line
      and the camera position. Also, vision parameters are deduced by the network and
      image processing. In this manner, the shape connection is achieved automatically
      by computational algorithms. Therefore, errors of physical measurement are not
      passed to the reconstruction system. Thus, the performance and the accuracy of
      the reconstruction system are improved. This is elucidated by the comparison
      between the obtained results by the proposed technique and the obtained results
      by a contact method. Thus, a contribution in laser metrology for shape connection
      is achieved.

PMID- 18617977
TI  - Optical analysis of time-averaged multiscale Bessel beams generated by a tunable
      acoustic gradient index of refraction lens.
AB  - Current methods for generating Bessel beams are limited to fixed beam sizes or,
      in the case of conventional adaptive optics, relatively long switching times
      between beam shapes. We analyze the multiscale Bessel beams created using an
      alternative rapidly switchable device: a tunable acoustic gradient index (TAG)
      lens. The shape of the beams and their nondiffracting, self-healing
      characteristics are studied experimentally and explained theoretically using both
      geometric and Fourier optics. By adjusting the electrical driving signal, we can
      tune the ring spacings, the size of the central spot, and the working distance of
      the lens. The results presented here will enable researchers to employ dynamic
      Bessel beams generated by TAG lenses.

PMID- 18617978
TI  - Modeling of nonphase mechanisms in ultrasonic modulation of light propagation.
AB  - While phase variation due to ultrasonic modulation of coherent light has been
      extensively studied in acousto-optical imaging, fewer groups have studied
      nonphase mechanisms of ultrasonic modulation, which may be important in exploring
      ultrasonic modulation of incoherent light for imaging. We have developed a
      versatile Monte Carlo based method that can model not only phase variation due to
      refractive index changes and scatterer displacement in tissue or tissue-like
      phantoms, but also amplitude and exit location variations due to the changes in
      optical properties and refractive index under ultrasonic modulation, in which the
      exit location variation has not, to the best of our knowledge, been modeled
      previously. Our results show that the modulation depth due to the exit location
      variation is three orders of magnitude higher than that due to amplitude
      variation, but two to three orders of magnitude lower than that due to phase
      variation for monochromatic light. Furthermore it is found that the modulation
      depth in reflectance due to the exit location variation is larger than that in
      transmittance for small source-detector separations.

PMID- 18617979
TI  - Calibration of force actuators on an adaptive secondary prototype.
AB  - In the context of the Large Binocular Telescope project, we present the results
      of force actuator calibrations performed on an adaptive secondary prototype
      called P45, a thin deformable glass with magnets glued onto its back.
      Electromagnetic actuators, controlled in a closed loop with a system of internal
      metrology based on capacitive sensors, continuously deform its shape to correct
      the distortions of the wavefront. Calibrations of the force actuators are needed
      because of the differences between driven forces and measured forces. We describe
      the calibration procedures and the results, obtained with errors of less than
      1.5%.

PMID- 18617980
TI  - Robust control of a bimorph mirror for adaptive optics systems.
AB  - We apply robust control techniques to an adaptive optics system including a
      dynamic model of the deformable mirror. The dynamic model of the mirror is a
      modification of the usual plate equation. We propose also a state-space approach
      to model the turbulent phase. A continuous time control of our model is
      suggested, taking into account the frequential behavior of the turbulent phase.
      An H(infinity) controller is designed in an infinite-dimensional setting. Because
      of the multivariable nature of the control problem involved in adaptive optics
      systems, a significant improvement is obtained with respect to traditional single
      input-single output methods.

PMID- 18617981
TI  - Development of the 2.8 microm emission doubly shifted Raman laser using
      stimulated Brillouin scattering in a cascaded cavity.
AB  - A doubly shifted Raman laser using CH(4) gas has been developed for 2.8 microm
      generation, pumped by a Nd:YAG laser with 65.5 mJ at 17 ns. A dichroically coated
      meniscus-type lens is modified to utilize the backward stimulated Brillouin
      scattering and backward Stokes beams from a previous laser design [Appl. Opt.46,
      5516-5521 (2007)APOPAI0003-693510.1364/AO.46.005516]. A maximum output energy of
      4.76 mJ at 2.80 microm wavelength has been achieved in the cascaded resonator. A
      maximum conversion efficiency of 8.9% has been achieved at a CH(4) gas pressure
      of 600 psi. The obtained spatial beam profile is quite smooth, and its output
      pulse width is 10 ns.

PMID- 18617982
TI  - Manifestation of active medium astigmatism at transverse mode locking in a diode
      end-pumped stable resonator laser.
AB  - Transverse mode locking in a diode end-pumped Nd:YAG laser with up to
      approximately 140 cm resonator length was investigated. It was found that for
      each resonator degeneracy, there are two degenerate lengths where the fundamental
      mode is very different from the Gaussian mode. Fundamental mode intensity
      patterns for these lengths expand in directions perpendicular to each other.
      Experimental results are in a good agreement with numerical calculations, taking
      into account active medium (AM) astigmatism and inhomogeneous gain. Optical
      powers of astigmatic AM can be found directly from measurements of degenerate
      lengths without using numerical modeling.

PMID- 18617983
TI  - Mechanical modeling of fluid-driven polymer lenses.
AB  - A finite-element model (FEM) is employed to study the pressure response of
      deformable elastic membranes used as tunable optical elements. The model is
      capable of determining in situ both the modulus and the prestrain from a
      measurement of peak deflection versus pressure. Given accurate values for modulus
      and prestrain, it is shown that the two parameters of a standard optical shape
      function (radius of curvature and conic constant) can be accurately predicted.
      The effects of prestrain in polydimethylsiloxane (PDMS) membranes are
      investigated in detail. It was found that prestrain reduces the sensitivity of
      the membrane shape to the details of the edge clamping. It also reduces the
      variation of the conic constant with changes in curvature. Thus the ability to
      control the prestrain as well as thickness and modulus is important to developing
      robust optical designs based on fluid-driven polymer lenses.

PMID- 18617984
TI  - Two-state model of light induced activation and thermal bleaching of photochromic
      glasses: theory and experiments.
AB  - The behavior of photochromic glasses during activation and bleaching is
      investigated. A two-state phenomenological model describing light-induced
      activation (darkening) and thermal bleaching is presented. The proposed model is
      based on first-order kinetics. We demonstrate that the time behavior in the
      activation process (acting simultaneously with the thermal fading) can be
      characterized by two relaxation times that depend on the intensity of the
      activating light. These characteristic times are lower than the decay times of
      the pure thermal bleaching process. We study the temporal evolution of the glass
      optical density and its dependence on the activating intensity. We also present a
      series of activation and bleaching experiments that validate the proposed model.
      Our approach may be used to gain more insight into the transmittance behavior of
      photosensitive glasses, which could be potentially relevant in a broad range of
      applications, e.g., real-time holography and reconfigurable optical memories.

PMID- 18617985
TI  - Speckle dynamics for intensity-modulated illumination.
AB  - We analyze the dynamics of laser speckle patterns, designed for sensing with a
      receiver, based on spatial filtering. The speckle translation arises after free
      space propagation of light scattered from nonspecular surfaces of a solid object
      in motion. The speckle pattern is manipulated by modulating the intensity of the
      coherent light, illuminating the target. The space-time normalized cross
      covariance of speckle patterns incident on the spatial sensor is calculated for
      the field distribution of three Gaussian beams having arbitrary directions and
      separations when incident on the target. The modulation of the intensity
      distribution at the target introduce a higher spatial frequency component in the
      speckle pattern. The theoretical analysis provides the statistical parameters for
      both the speckles and the higher spatial frequency component. The analysis
      reveals that the speckles and the higher spatial frequency component do not
      necessarily translate as a rigid structure. The theoretical findings are
      supported by measurements.

PMID- 18617986
TI  - Frequency conversion to the second harmonic in different-layer nonlinear media.
AB  - The process of frequency conversion in a multilayer structure of different media
      with quadratic nonlinearity is investigated by using the constant-intensity
      approximation. The values of complex amplitudes of the fundamental radiation and
      the second harmonic at the outlet of each layer are the entrance values of the
      corresponding complex amplitudes of the next layer. Analytical expressions for
      second-harmonic conversion efficiency for the case of n layers are proposed. The
      factors restricting the efficiency of the process of frequency conversion are
      analyzed. In layered media, upon frequency conversion, from one layer to the next
      the optimum values of the phase mismatch between layers changes. The character of
      the process of frequency conversion of the fundamental radiation to the second
      harmonic depends not only on the value of the nonlinear coefficients of waves,
      the phase mismatch, but also on the signs of these parameters.

PMID- 18617987
TI  - Some Geometric Methods for Constructing Decision Criteria Based On Two
      Dimensional Parameters.
AB  - This paper reviews two types of geometric methods proposed in recent years for
      defining statistical decision rules based on 2-dimensional parameters that
      characterize treatment effect in a medical setting. A common example is that of
      making decisions, such as comparing treatments or selecting a best dose, based on
      both the probability of efficacy and the probability toxicity. In most
      applications, the 2-dimensional parameter is defined in terms of a model
      parameter of higher dimension including effects of treatment and possibly
      covariates. Each method uses a geometric construct in the 2-dimensional parameter
      space based on a set of elicited parameter pairs as a basis for defining decision
      rules. The first construct is a family of contours that partitions the parameter
      space, with the contours constructed so that all parameter pairs on a given
      contour are equally desirable. The partition is used to define statistical
      decision rules that discriminate between parameter pairs in term of their
      desirabilities. The second construct is a convex 2-dimensional set of desirable
      parameter pairs, with decisions based on posterior probabilities of this set for
      given combinations of treatments and covariates under a Bayesian formulation. A
      general framework for all of these methods is provided, and each method is
      illustrated by one or more applications.

PMID- 18617989
TI  - Evolution of evolvability in gene regulatory networks.
AB  - Gene regulatory networks are perhaps the most important organizational level in
      the cell where signals from the cell state and the outside environment are
      integrated in terms of activation and inhibition of genes. For the last decade,
      the study of such networks has been fueled by large-scale experiments and renewed
      attention from the theoretical field. Different models have been proposed to, for
      instance, investigate expression dynamics, explain the network topology we
      observe in bacteria and yeast, and for the analysis of evolvability and
      robustness of such networks. Yet how these gene regulatory networks evolve and
      become evolvable remains an open question. An individual-oriented evolutionary
      model is used to shed light on this matter. Each individual has a genome from
      which its gene regulatory network is derived. Mutations, such as gene
      duplications and deletions, alter the genome, while the resulting network
      determines the gene expression pattern and hence fitness. With this protocol we
      let a population of individuals evolve under Darwinian selection in an
      environment that changes through time. Our work demonstrates that long-term
      evolution of complex gene regulatory networks in a changing environment can lead
      to a striking increase in the efficiency of generating beneficial mutations. We
      show that the population evolves towards genotype-phenotype mappings that allow
      for an orchestrated network-wide change in the gene expression pattern, requiring
      only a few specific gene indels. The genes involved are hubs of the networks, or
      directly influencing the hubs. Moreover, throughout the evolutionary trajectory
      the networks maintain their mutational robustness. In other words, evolution in
      an alternating environment leads to a network that is sensitive to a small class
      of beneficial mutations, while the majority of mutations remain neutral: an
      example of evolution of evolvability.

PMID- 18617988
TI  - Unraveling protein networks with power graph analysis.
AB  - Networks play a crucial role in computational biology, yet their analysis and
      representation is still an open problem. Power Graph Analysis is a lossless
      transformation of biological networks into a compact, less redundant
      representation, exploiting the abundance of cliques and bicliques as elementary
      topological motifs. We demonstrate with five examples the advantages of Power
      Graph Analysis. Investigating protein-protein interaction networks, we show how
      the catalytic subunits of the casein kinase II complex are distinguishable from
      the regulatory subunits, how interaction profiles and sequence phylogeny of SH3
      domains correlate, and how false positive interactions among high-throughput
      interactions are spotted. Additionally, we demonstrate the generality of Power
      Graph Analysis by applying it to two other types of networks. We show how power
      graphs induce a clustering of both transcription factors and target genes in
      bipartite transcription networks, and how the erosion of a phosphatase domain in
      type 22 non-receptor tyrosine phosphatases is detected. We apply Power Graph
      Analysis to high-throughput protein interaction networks and show that up to 85%
      (56% on average) of the information is redundant. Experimental networks are more
      compressible than rewired ones of same degree distribution, indicating that
      experimental networks are rich in cliques and bicliques. Power Graphs are a novel
      representation of networks, which reduces network complexity by explicitly
      representing re-occurring network motifs. Power Graphs compress up to 85% of the
      edges in protein interaction networks and are applicable to all types of networks
      such as protein interactions, regulatory networks, or homology networks.

PMID- 18617990
TI  - Active nuclear receptors exhibit highly correlated AF-2 domain motions.
AB  - Nuclear receptor ligand binding domains (LBDs) convert ligand binding events into
      changes in gene expression by recruiting transcriptional coregulators to a
      conserved activation function-2 (AF-2) surface. While most nuclear receptor LBDs
      form homo- or heterodimers, the human nuclear receptor pregnane X receptor (PXR)
      forms a unique and essential homodimer and is proposed to assemble into a
      functional heterotetramer with the retinoid X receptor (RXR). How the homodimer
      interface, which is located 30 A from the AF-2, would affect function at this
      critical surface has remained unclear. By using 20- to 30-ns molecular dynamics
      simulations on PXR in various oligomerization states, we observed a remarkably
      high degree of correlated motion in the PXR-RXR heterotetramer, most notably in
      the four helices that create the AF-2 domain. The function of such correlation
      may be to create "active-capable" receptor complexes that are ready to bind to
      transcriptional coactivators. Indeed, we found in additional simulations that
      active-capable receptor complexes involving other orphan or steroid nuclear
      receptors also exhibit highly correlated AF-2 domain motions. We further propose
      a mechanism for the transmission of long-range motions through the nuclear
      receptor LBD to the AF-2 surface. Taken together, our findings indicate that long
      range motions within the LBD scaffold are critical to nuclear receptor function
      by promoting a mobile AF-2 state ready to bind coactivators.

PMID- 18617991
TI  - Lysis of endogenously infected CD4+ T cell blasts by rIL-2 activated autologous
      natural killer cells from HIV-infected viremic individuals.
AB  - Understanding the cellular mechanisms that ensure an appropriate innate immune
      response against viral pathogens is an important challenge of biomedical
      research. In vitro studies have shown that natural killer (NK) cells purified
      from healthy donors can kill heterologous cell lines or autologous CD4+ T cell
      blasts exogenously infected with several strains of HIV-1. However, it is not
      known whether the deleterious effects of high HIV-1 viremia interferes with the
      NK cell-mediated cytolysis of autologous, endogenously HIV-1-infected CD4+ T
      cells. Here, we stimulate primary CD4+ T cells, purified ex vivo from HIV-1
      infected viremic patients, with PHA and rIL2 (with or without rIL-7). This
      experimental procedure allows for the significant expansion and isolation of
      endogenously infected CD4+ T cell blasts detected by intracellular staining of
      p24 HIV-1 core antigen. We show that, subsequent to the selective down-modulation
      of MHC class-I (MHC-I) molecules, HIV-1-infected p24(pos) blasts become partially
      susceptible to lysis by rIL-2-activated NK cells, while uninfected p24(neg)
      blasts are spared from killing. This NK cell-mediated killing occurs mainly
      through the NKG2D activation pathway. However, the degree of NK cell cytolytic
      activity against autologous, endogenously HIV-1-infected CD4+ T cell blasts that
      down-modulate HLA-A and -B alleles and against heterologous MHC-I(neg) cell lines
      is particularly low. This phenomenon is associated with the defective surface
      expression and engagement of natural cytotoxicity receptors (NCRs) and with the
      high frequency of the anergic CD56(neg)/CD16(pos) subsets of highly dysfunctional
      NK cells from HIV-1-infected viremic patients. Collectively, our data demonstrate
      that the chronic viral replication of HIV-1 in infected individuals results in
      several phenotypic and functional aberrancies that interfere with the NK cell
      mediated killing of autologous p24(pos) blasts derived from primary T cells.

PMID- 18617992
TI  - RIG-I mediates the co-induction of tumor necrosis factor and type I interferon
      elicited by myxoma virus in primary human macrophages.
AB  - The sensing of pathogen infection and subsequent triggering of innate immunity
      are key to controlling zoonotic infections. Myxoma virus (MV) is a cytoplasmic
      DNA poxvirus that in nature infects only rabbits. Our previous studies have shown
      that MV infection of primary mouse cells is restricted by virus-induced type I
      interferon (IFN). However, little is known about the innate sensor(s) involved in
      activating signaling pathways leading to cellular defense responses in primary
      human immune cells. Here, we show that the complete restriction of MV infection
      in the primary human fibroblasts requires both tumor necrosis factor (TNF) and
      type I IFN. We also demonstrate that MV infection of primary human macrophages
      (pHMs) activates the cytoplasmic RNA sensor called retinoic acid inducible gene I
      (RIG-I), which coordinately induces the production of both TNF and type I IFN. Of
      note, RIG-I sensing of MV infection in pHMs initiates a sustained TNF induction
      through the sequential involvement of the downstream IFN-regulatory factors 3 and
      7 (IRF3 and IRF7). Thus, RIG-I-mediated co-induction of TNF and type I IFN by
      virus-infected pHMs represents a novel innate defense mechanism to restrict viral
      infection in human cells. These results also reveal a new regulatory mechanism
      for TNF induction following viral infection.

PMID- 18617993
TI  - Genome-wide screen of three herpesviruses for protein subcellular localization
      and alteration of PML nuclear bodies.
AB  - Herpesviruses are large, ubiquitous DNA viruses with complex host interactions,
      yet many of the proteins encoded by these viruses have not been functionally
      characterized. As a first step in functional characterization, we determined the
      subcellular localization of 234 epitope-tagged proteins from herpes simplex
      virus, cytomegalovirus, and Epstein-Barr virus. Twenty-four of the 93 proteins
      with nuclear localization formed subnuclear structures. Twelve of these localized
      to the nucleolus, and five at least partially localized with promyelocytic
      leukemia (PML) bodies, which are known to suppress viral lytic infection. In
      addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins
      significantly decreased the number of PML bodies per cell, including six that
      were shown to be SUMO-modified. These results have provided the first functional
      insights into over 120 previously unstudied proteins and suggest that
      herpesviruses employ multiple strategies for manipulating nuclear bodies that
      control key cellular processes.

PMID- 18617994
TI  - Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza
      viruses.
AB  - Genetic reassortment of H5N1 highly pathogenic avian influenza viruses (HPAI)
      with currently circulating human influenza A strains is one possibility that
      could lead to efficient human-to-human transmissibility. Domestic pigs which are
      susceptible to infection with both human and avian influenza A viruses are one of
      the natural hosts where such reassortment events could occur. Virological,
      histological and serological features of H5N1 virus infection in pigs were
      characterized in this study. Two- to three-week-old domestic piglets were
      intranasally inoculated with 10(6) EID(50) of A/Vietnam/1203/04 (VN/04),
      A/chicken/Indonesia/7/03 (Ck/Indo/03), A/Whooper swan/Mongolia/244/05
      (WS/Mong/05), and A/Muscovy duck/Vietnam/ 209/05 (MDk/VN/05) viruses. Swine H3N2
      and H1N1 viruses were studied as a positive control for swine influenza virus
      infection. The pathogenicity of the H5N1 HPAI viruses was also characterized in
      mouse and ferret animal models. Intranasal inoculation of pigs with H5N1 viruses
      or consumption of infected chicken meat did not result in severe disease. Mild
      weight loss was seen in pigs inoculated with WS/Mong/05, Ck/Indo/03 H5N1 and H1N1
      swine influenza viruses. WS/Mong/05, Ck/Indo/03 and VN/04 viruses were detected
      in nasal swabs of inoculated pigs mainly on days 1 and 3. Titers of H5N1 viruses
      in nasal swabs were remarkably lower compared with those of swine influenza
      viruses. Replication of all four H5N1 viruses in pigs was restricted to the
      respiratory tract, mainly to the lungs. Titers of H5N1 viruses in the lungs were
      lower than those of swine viruses. WS/Mong/05 virus was isolated from trachea and
      tonsils, and MDk/VN/05 virus was isolated from nasal turbinate of infected pigs.
      Histological examination revealed mild to moderate bronchiolitis and multifocal
      alveolitis in the lungs of pigs infected with H5N1 viruses, while infection with
      swine influenza viruses resulted in severe tracheobronchitis and
      bronchointerstitial pneumonia. Pigs had low susceptibility to infection with H5N1
      HPAI viruses. Inoculation of pigs with H5N1 viruses resulted in asymptomatic to
      mild symptomatic infection restricted to the respiratory tract and tonsils in
      contrast to mouse and ferrets animal models, where some of the viruses studied
      were highly pathogenic and replicated systemically.

PMID- 18617995
TI  - Antibodies targeting the PfRH1 binding domain inhibit invasion of Plasmodium
      falciparum merozoites.
AB  - Invasion by the malaria merozoite depends on recognition of specific erythrocyte
      surface receptors by parasite ligands. Plasmodium falciparum uses multiple
      ligands, including at least two gene families, reticulocyte binding protein
      homologues (RBLs) and erythrocyte binding proteins/ligands (EBLs). The
      combination of different RBLs and EBLs expressed in a merozoite defines the
      invasion pathway utilized and could also play a role in parasite virulence. The
      binding regions of EBLs lie in a conserved cysteine-rich domain while the binding
      domain of RBL is still not well characterized. Here, we identify the erythrocyte
      binding region of the P. falciparum reticulocyte binding protein homologue 1
      (PfRH1) and show that antibodies raised against the functional binding region
      efficiently inhibit invasion. In addition, we directly demonstrate that changes
      in the expression of RBLs can constitute an immune evasion mechanism of the
      malaria merozoite.

PMID- 18617996
TI  - Mechanisms of cell cycle control revealed by a systematic and quantitative
      overexpression screen in S. cerevisiae.
AB  - Regulation of cell cycle progression is fundamental to cell health and
      reproduction, and failures in this process are associated with many human
      diseases. Much of our knowledge of cell cycle regulators derives from loss-of
      function studies. To reveal new cell cycle regulatory genes that are difficult to
      identify in loss-of-function studies, we performed a near-genome-wide flow
      cytometry assay of yeast gene overexpression-induced cell cycle delay phenotypes.
      We identified 108 genes whose overexpression significantly delayed the
      progression of the yeast cell cycle at a specific stage. Many of the genes are
      newly implicated in cell cycle progression, for example SKO1, RFA1, and YPR015C.
      The overexpression of RFA1 or YPR015C delayed the cell cycle at G2/M phases by
      disrupting spindle attachment to chromosomes and activating the DNA damage
      checkpoint, respectively. In contrast, overexpression of the transcription factor
      SKO1 arrests cells at G1 phase by activating the pheromone response pathway,
      revealing new cross-talk between osmotic sensing and mating. More generally, 92%
      94% of the genes exhibit distinct phenotypes when overexpressed as compared to
      their corresponding deletion mutants, supporting the notion that many genes may
      gain functions upon overexpression. This work thus implicates new genes in cell
      cycle progression, complements previous screens, and lays the foundation for
      future experiments to define more precisely roles for these genes in cell cycle
      progression.

PMID- 18617997
TI  - The recombinational anatomy of a mouse chromosome.
AB  - Among mammals, genetic recombination occurs at highly delimited sites known as
      recombination hotspots. They are typically 1-2 kb long and vary as much as a
      1,000-fold or more in recombination activity. Although much is known about the
      molecular details of the recombination process itself, the factors determining
      the location and relative activity of hotspots are poorly understood. To further
      our understanding, we have collected and mapped the locations of 5,472 crossover
      events along mouse Chromosome 1 arising in 6,028 meioses of male and female
      reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. Crossovers were mapped to a
      minimum resolution of 225 kb, and those in the telomere-proximal 24.7 Mb were
      further mapped to resolve individual hotspots. Recombination rates were
      evolutionarily conserved on a regional scale, but not at the local level. There
      was a clear negative-exponential relationship between the relative activity and
      abundance of hotspot activity classes, such that a small number of the most
      active hotspots account for the majority of recombination. Females had 1.2x
      higher overall recombination than males did, although the sex ratio showed
      considerable regional variation. Locally, entirely sex-specific hotspots were
      rare. The initiation of recombination at the most active hotspot was regulated
      independently on the two parental chromatids, and analysis of reciprocal crosses
      indicated that parental imprinting has subtle effects on recombination rates. It
      appears that the regulation of mammalian recombination is a complex, dynamic
      process involving multiple factors reflecting species, sex, individual variation
      within species, and the properties of individual hotspots.

PMID- 18617998
TI  - Identification and dissection of a complex DNA repair sensitivity phenotype in
      Baker's yeast.
AB  - Complex traits typically involve the contribution of multiple gene variants. In
      this study, we took advantage of a high-density genotyping analysis of the BY
      (S288c) and RM strains of Saccharomyces cerevisiae and of 123 derived spore
      progeny to identify the genetic loci that underlie a complex DNA repair
      sensitivity phenotype. This was accomplished by screening hybrid yeast progeny
      for sensitivity to a variety of DNA damaging agents. Both the BY and RM strains
      are resistant to the ultraviolet light-mimetic agent 4-nitroquinoline 1-oxide (4
      NQO); however, hybrid progeny from a BYxRM cross displayed varying sensitivities
      to the drug. We mapped a major quantitative trait locus (QTL), RAD5, and
      identified the exact polymorphism within this locus responsible for 4-NQO
      sensitivity. By using a backcrossing strategy along with array-assisted bulk
      segregant analysis, we identified one other locus, MKT1, and a QTL on Chromosome
      VII that also link to the hybrid 4-NQO-sensitive phenotype but confer more minor
      effects. This work suggests an additive model for sensitivity to 4-NQO and
      provides a strategy for mapping both major and minor QTL that confer background
      specific phenotypes. It also provides tools for understanding the effect of
      genetic background on sensitivity to genotoxic agents.

PMID- 18617999
TI  - The generation of promoter-mediated transcriptional noise in bacteria.
AB  - Noise in the expression of a gene produces fluctuations in the concentration of
      the gene product. These fluctuations can interfere with optimal function or can
      be exploited to generate beneficial diversity between cells; gene expression
      noise is therefore expected to be subject to evolutionary pressure. Shifts
      between modes of high and low rates of transcription initiation at a promoter
      appear to contribute to this noise both in eukaryotes and prokaryotes. However,
      models invoked for eukaryotic promoter noise such as stable activation scaffolds
      or persistent nucleosome alterations seem unlikely to apply to prokaryotic
      promoters. We consider the relative importance of the steps required for
      transcription initiation. The 3-step transcription initiation model of McClure is
      extended into a mathematical model that can be used to predict consequences of
      additional promoter properties. We show in principle that the transcriptional
      bursting observed at an E. coli promoter by Golding et al. (2005) can be
      explained by stimulation of initiation by the negative supercoiling behind a
      transcribing RNA polymerase (RNAP) or by the formation of moribund or dead-end
      RNAP-promoter complexes. Both mechanisms are tunable by the alteration of
      promoter kinetics and therefore allow the optimization of promoter mediated
      noise.

PMID- 18618000
TI  - A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for
      age-dependent nicotine addiction.
AB  - People who begin daily smoking at an early age are at greater risk of long-term
      nicotine addiction. We tested the hypothesis that associations between nicotinic
      acetylcholine receptor (nAChR) genetic variants and nicotine dependence assessed
      in adulthood will be stronger among smokers who began daily nicotine exposure
      during adolescence. We compared nicotine addiction-measured by the Fagerstrom
      Test of Nicotine Dependence-in three cohorts of long-term smokers recruited in
      Utah, Wisconsin, and by the NHLBI Lung Health Study, using a candidate-gene
      approach with the neuronal nAChR subunit genes. This SNP panel included common
      coding variants and haplotypes detected in eight alpha and three beta nAChR
      subunit genes found in European American populations. In the 2,827 long-term
      smokers examined, common susceptibility and protective haplotypes at the CHRNA5
      A3-B4 locus were associated with nicotine dependence severity (p = 2.0x10(-5);
      odds ratio = 1.82; 95% confidence interval 1.39-2.39) in subjects who began daily
      smoking at or before the age of 16, an exposure period that results in a more
      severe form of adult nicotine dependence. A substantial shift in susceptibility
      versus protective diplotype frequency (AA versus BC = 17%, AA versus CC = 27%)
      was observed in the group that began smoking by age 16. This genetic effect was
      not observed in subjects who began daily nicotine use after the age of 16. These
      results establish a strong mechanistic link among early nicotine exposure, common
      CHRNA5-A3-B4 haplotypes, and adult nicotine addiction in three independent
      populations of European origins. The identification of an age-dependent
      susceptibility haplotype reinforces the importance of preventing early exposure
      to tobacco through public health policies.

PMID- 18618002
TI  - In vitro assessment of optical properties of blood by applying the extended
      Huygens-Fresnel principle to time-domain optical coherence tomography signal at
      1300 nm.
AB  - A direct method for the measurement of the optical attenuation coefficient and
      the scattering anisotropy parameter based on applying the extended Huygens
      Fresnel principle to optical coherence tomography images of blood is
      demonstrated. The images are acquired with a low-power probing beam at the
      wavelength of 1300 nm. Values of 12.15 mm(-1) and 0.95 are found for the total
      attenuation coefficient and the scattering anisotropy factor, respectively. Also,
      as a preliminary step, the optical refraction index is determined with a
      precision of two decimal numbers directly from optical coherence images. The
      total attenuation coefficient and the scattering anisotropy factor are determined
      with precisions within experimental error margins of 5% and 2%, respectively.
      Readable OCT signal is obtained for a maximum propagation of light into blood of
      0.25 mm. At the maximum probed depth, the measured signal is almost 10(3) smaller
      than its initial intensity when entering the sample.

PMID- 18618001
TI  - Zebrafish whole-adult-organism chemogenomics for large-scale predictive and
      discovery chemical biology.
AB  - The ability to perform large-scale, expression-based chemogenomics on whole adult
      organisms, as in invertebrate models (worm and fly), is highly desirable for a
      vertebrate model but its feasibility and potential has not been demonstrated. We
      performed expression-based chemogenomics on the whole adult organism of a
      vertebrate model, the zebrafish, and demonstrated its potential for large-scale
      predictive and discovery chemical biology. Focusing on two classes of compounds
      with wide implications to human health, polycyclic (halogenated) aromatic
      hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust
      prediction models that can discriminate compounds of the same class from those of
      different classes in two large independent experiments. The robust expression
      signatures led to the identification of biomarkers for potent aryl hydrocarbon
      receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were
      validated in multiple targeted tissues. Knowledge-based data mining of human
      homologs of zebrafish genes revealed highly conserved chemical-induced biological
      responses/effects, health risks, and novel biological insights associated with
      AHR and ER that could be inferred to humans. Thus, our study presents an
      effective, high-throughput strategy of capturing molecular snapshots of chemical
      induced biological states of a whole adult vertebrate that provides information
      on biomarkers of effects, deregulated signaling pathways, and possible affected
      biological functions, perturbed physiological systems, and increased health
      risks. These findings place zebrafish in a strategic position to bridge the wide
      gap between cell-based and rodent models in chemogenomics research and
      applications, especially in preclinical drug discovery and toxicology.

PMID- 18618003
TI  - Exfoliation syndrome and exfoliation glaucoma-associated LOXL1 variations are not
      involved in pigment dispersion syndrome and pigmentary glaucoma.
AB  - PURPOSE: Single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been
      implicated in exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). We have
      shown that these SNPs are not associated with the primary glaucomas such as
      primary open-angle (POAG) glaucoma and primary angle-closure glaucoma (PACG). To
      further establish the specificity of LOXL1 SNPs for XFS and XFG, we determined
      whether these SNPs were involved in pigment dispersion syndrome (PDS) and
      pigmentary glaucoma (PG). METHODS: Three SNPs of LOXL1 (rs1048661, rs3825942, and
      rs2165241) were screened in a cohort of 78 unrelated and clinically well
      characterized glaucoma cases comprising of PG (n=44) and PDS (n=34) patients as
      well as 108 ethnically matched normal controls of Caucasian origin. The criteria
      for diagnosis of PDS/PG were Krukenberg spindle, hyperpigmentation of the
      trabecular meshwork, and wide open angle. Transillumination defects were detected
      by infrared pupillography, and the presence of a Zentmayer ring was considered as
      a confirmatory sign. All three SNPs were genotyped in cases and controls by
      resequencing the genomic region of LOXL1 harboring these variants and were
      further confirmed by polymerase chain reaction (PCR)-based restriction
      digestions. Haplotypes were generated from the genotype data, and the linkage
      disequilibrium (LD) and haplotype analysis were done with Haploview software that
      uses the expectation maximization (EM) algorithm. RESULTS: The LOXL1 SNPs showed
      no significant association with PDS or PG. There was no significant difference in
      the frequencies of the risk alleles of rs1048661 ('G' allele; p=0.309), rs3825942
      ('G' allele' p=0.461), and rs2165241 ('T' allele; p=0.432) between PG/PDS cases
      and controls. Similarly, there was no involvement of the XFS/XFG-associated
      haplotypes, 'G-G' (p=0.643; [OR=1.08, 95%CI, 0.59-1.97]) and 'T-G' (p=0.266;
      [OR=1.35, 95%CI, 0.70-2.60]), with the PDS/PG phenotypes. The risk haplotype 'G
      G' was observed in ~55% of the normal controls. CONCLUSIONS: There was no
      involvement of the LOXL1 SNPs in patients with PDS and PG. The results further
      indicate that the associations of these SNPs are specific to XFS/XFG.

PMID- 18618004
TI  - Analysis of conjunctival fibroblasts from a proband with Schnyder corneal
      dystrophy.
AB  - PURPOSE: To analyze for the presence of lipids in conjunctival fibroblasts of a
      patient with Schnyder corneal dystrophy (SCD). METHODS: A proband with SCD was
      identified, and the pedigree was examined. The proband underwent an automated
      lamellar therapeutic keratoplasty (ALTK). At the same time, the proband underwent
      a skin and conjunctival biopsy. Specimens were sent for histological and
      ultrastructural examination. Conjunctival fibroblasts were cultured from the
      biopsy specimen and stained with filipin. RESULTS: The proband showed no evidence
      of recurrence following the ALTK procedure. Histopathological examination showed
      no evidence of hydrophobic lipids in the conjunctival or dermal fibroblasts.
      Lipid particles were detected in the cornea. Ultrastructural examination showed
      no lipid particles in the conjunctival fibroblasts. Cultured fibroblasts showed
      no evidence of intracellular unesterified cholesterol unless low density
      lipoprotein (LDL) was added to the culture medium. CONCLUSIONS: There was no
      evidence of lipid deposition in conjunctival or skin fibroblasts in our patient
      with SCD. The evidence suggests local factors are responsible for the lipid
      deposition in the cornea.

PMID- 18618005
TI  - A nonsense mutation in CRYGC associated with autosomal dominant congenital
      nuclear cataract in a Chinese family.
AB  - PURPOSE: To identify the genetic defect associated with autosomal dominant
      congenital nuclear cataract in a Chinese family. METHODS: Family history and
      phenotypic data were recorded, and the phenotypes were documented by slit lamp
      photography. The genomic DNA was extracted from peripheral blood leukocytes. All
      the exons and flanking intronic sequences of CRYGC and CRYGD were amplified by
      polymerase chain reaction (PCR) and screened for mutation by direct DNA
      sequencing. Structural models of the wild type and mutant gammaC-crystallin were
      generated and analyzed by SWISS-MODEL. RESULTS: Sequencing of the coding regions
      of CRYGC and CRYGD showed the presence of a heterozygous C>A transversion at
      c.327 of the coding sequence in exon 3 of CRYGC (c.327C>A), which results in the
      substitution of a wild type cysteine to a nonsense codon (C109X). One and a half
      Greek key motifs at the COOH-terminus were found to be absent in the structural
      model of the mutant truncated gammaC-crystallin. CONCLUSIONS: A novel nonsense
      mutation in CRYGC was detected in a Chinese family with consistent autosomal
      dominant congenital nuclear cataract, providing clear evidence of a relationship
      between the genotype and the corresponding cataract phenotype.

PMID- 18618006
TI  - The application of in vivo laser confocal microscopy to the diagnosis and
      evaluation of meibomian gland dysfunction.
AB  - PURPOSE: To evaluate the morphological changes of the meibomian glands (MG) in
      patients with meibomian gland dysfunction (MGD) compared to normal subjects by in
      vivo confocal microscopy and to investigate the relation of these changes to the
      clinical ocular surface findings and tear functions. METHODS: Twenty MGD patients
      and 15 normal subjects were recruited into this prospective study. Patients and
      controls underwent slit lamp examinations, tear film break-up time (BUT)
      measurements, fluorescein and Rose-Bengal stainings, Schirmer test I without
      anesthesia, tear evaporation rate assessment (TEROS), tear film lipid layer
      interferometry (DR-1), transillumination of the lids (meibography), MG
      expressibility test, and in vivo laser confocal microscopy of the lids (HRTII
      RCM). RESULTS: The BUT, DR-1 tear film lipid layer interferometry grades,
      fluorescein and Rose-Bengal staining scores, MG drop out grade in meibography,
      and MG expressibility grades were significantly worse in MGD patients compared to
      normal controls (p<0.05). The severity of both MG dropout and MG expressibility
      related significantly with the BUT, DR-1 grades, and TEROS (p<0.05). The mean
      density of acinar units of MGs as measured by HRTII-RCM was significantly lower
      in MGD patients (47.6+/-26.6/mm(2)) than in control subjects (101.3+/-33.8/mm(2);
      p<0.05). The mean acinar unit diameter as determined by HRTII-RCM was
      significantly larger in MGD patients (98.2+/-53.3 mum) than in controls (41.6+/
      11.9 mum; p<0.05). Both the density and diameter of MG acinar units related
      significantly with the severity of MG dropout and MG expression grades (p<0.05).
      CONCLUSIONS: In vivo confocal microscopy can effectively demonstrate the
      morphological changes of the MG in patients with MGD. Glandular acinar density
      and acinar unit diameter seemed to be promising new parameters of in vivo
      confocal microscopy, which is significantly related to the clinical ocular
      surface and tear function findings of MGD.

PMID- 18618007
TI  - Protein-protein interactions between lens vimentin and alphaB-crystallin using
      FRET acceptor photobleaching.
AB  - PURPOSE: The R120G mutation of alphaB-crystallin is known to cause desmin-related
      myopathy, but the mechanisms underlying the formation of cataract are not clearly
      established. We hypothesize that alteration of protein-protein interaction
      between R120G alphaB-crystallin and lens intermediate filament proteins is one of
      the mechanisms of congenital cataract. METHODS: Protein-protein interactions were
      determined by confocal fluorescence resonance energy transfer (FRET) microscopy
      using green fluorescence protein (GFP) as the donor and red fluorescence protein
      (RFP) as the acceptor. The lens vimentin gene was fused into a GFP vector and the
      alphaB-crystallin (WT or R120G mutant) gene was fused into the RFP vector. The
      donor-acceptor plasmid pairs of intermediate filament (IF)-GFP and alphaB-RFP
      were co-transfected into HeLa cells. After incubation, confocal fluorescence
      images of the transfected cells were taken. FRET was estimated by the acceptor
      photobleaching method. Protein-protein interaction was evaluated by FRET
      efficiency. RESULTS: The confocal fluorescence images showed that the cells
      expressing vimentin and R120G alphaB-crystallin contained large amounts of
      protein aggregates while few vimentin fibers were observed. FRET efficiency
      analyses indicated that vimentin had a significantly greater protein-protein
      interaction with R120G alphaB-crystallin than with WT alphaB-crystallin.
      CONCLUSIONS: Our results show that the R120G alphaB-crystallin mutant promoted
      vimentin aggregation through increased protein-protein interaction. This process
      may contribute to the formation of congenital cataract.

PMID- 18618008
TI  - Effects of Mirtogenol on ocular blood flow and intraocular hypertension in
      asymptomatic subjects.
AB  - PURPOSE: The most important variable risk factor for developing glaucoma is
      intraocular hypertension. Timely lowering of high intraocular pressure (IOP)
      significantly lowers the likelihood of developing glaucoma. The aim of this study
      was to evaluate the effects of the food supplement Mirtogenol (Mirtoselect and
      Pycnogenol on IOP and ocular blood flow in a product evaluation study. METHODS:
      Thirty-eight asymptomatic subjects with intraocular hypertension were either
      given Mirtogenol (20 subjects) or were not treated (18 subjects). The visual
      acuity, IOP, and ocular blood flow were measured at two, three, and six months.
      RESULTS: After two months of supplementation with Mirtogenol, the mean IOP
      decreased from a baseline of 25.2 mmHg to 22.2 mmHg. After three months of
      treatment with Mirtogenol, the IOP was significantly lowered compared to that of
      untreated controls (p<0.05) to 22.0 mmHg. No further improvement was found after
      six months. Nineteen of the twenty patients taking Mirtogenol had a decreased IOP
      after three months. Only marginal effects on the IOP were found in the 18 control
      subjects. No side effects were observed. Ocular blood flow (central retinal,
      ophthalmic, and posterior ciliary arteries) improved both in the systolic and
      diastolic components as measured by Color Doppler imaging. After three months of
      treatment, the improvement of ocular blood flow was significant as compared to
      both baseline and control group (p<0.05). CONCLUSIONS: An improved ocular blood
      flow may contribute to the prevention of glaucoma. The results of this study
      indicate that Mirtogenol may represent a safe preventative intervention for
      lowering the risk for developing symptomatic glaucoma by controlling IOP and
      improving ocular blood flow.

PMID- 18618009
TI  - High throughput synthesis of peptides and peptidomimetics.
AB  - Peptide synthesis has been developed into one of the most efficient synthetic
      procedures in organic chemistry. The problems of orthogonal functional group
      protection and amide bond formation without racemization have been developed in a
      number of ingenious strategies. Optimization, in particular, has been achieved in
      stepwise solid phase synthesis. This in turn made possible the development of
      combinatorial synthesis allowing the synthesis of millions of peptide compounds
      of high purity in a few days. A variety of methodologies and strategies have been
      developed and continue to be developed to determine structures and to evaluate
      peptides and peptidomimetics. The development of methods for solid phase
      synthesis of a variety of organic and inorganic structures using similar
      strategies as in peptide synthesis are being vigorously pursued. However,
      existing instrumentation and technology is not sufficient to cover current
      demands for peptides, and thus new approaches and technologies for cost-effective
      synthesis of peptide arrays are needed.

PMID- 18618010
TI  - Classes of complex networks defined by role-to-role connectivity profiles.
AB  - In physical, biological, technological and social systems, interactions between
      units give rise to intricate networks. These-typically non-trivial-structures, in
      turn, critically affect the dynamics and properties of the system. The focus of
      most current research on complex networks is, still, on global network
      properties. A caveat of this approach is that the relevance of global properties
      hinges on the premise that networks are homogeneous, whereas most real-world
      networks have a markedly modular structure. Here, we report that networks with
      different functions, including the Internet, metabolic, air transportation and
      protein interaction networks, have distinct patterns of connections among nodes
      with different roles, and that, as a consequence, complex networks can be
      classified into two distinct functional classes on the basis of their link type
      frequency. Importantly, we demonstrate that these structural features cannot be
      captured by means of often studied global properties.

PMID- 18618011
TI  - Perceptions of Americans and the Iraq Invasion: Implications for Understanding
      National Character Stereotypes.
AB  - This study examines perceptions of the "typical American" from 49 cultures around
      the world. Contrary to the ethnocentric bias hypothesis, we found strong
      agreement between in-group and out-group ratings on the American profile
      (assertive, open-minded, but antagonistic); Americans in fact had a somewhat less
      desirable view of Americans than did others. Within cultures, in-group ratings
      were not systematically more favorable than out-group ratings. The Iraq invasion
      had a slight negative effect on perceptions of the typical American, but people
      around the world seem to draw a clear distinction between U.S. foreign policy and
      the character of the American people. National character stereotypes appear to
      have a variety of sources and to be perpetuated by both cognitive mechanisms and
      socio-cultural forces.

PMID- 18618012
TI  - Bayesian Weibull tree models for survival analysis of clinico-genomic data.
AB  - An important goal of research involving gene expression data for outcome
      prediction is to establish the ability of genomic data to define clinically
      relevant risk factors. Recent studies have demonstrated that microarray data can
      successfully cluster patients into low- and high-risk categories. However, the
      need exists for models which examine how genomic predictors interact with
      existing clinical factors and provide personalized outcome predictions. We have
      developed clinico-genomic tree models for survival outcomes which use recursive
      partitioning to subdivide the current data set into homogeneous subgroups of
      patients, each with a specific Weibull survival distribution. These trees can
      provide personalized predictive distributions of the probability of survival for
      individuals of interest. Our strategy is to fit multiple models; within each
      model we adopt a prior on the Weibull scale parameter and update this prior via
      Empirical Bayes whenever the sample is split at a given node. The decision to
      split is based on a Bayes factor criterion. The resulting trees are weighted
      according to their relative likelihood values and predictions are made by
      averaging over models. In a pilot study of survival in advanced stage ovarian
      cancer we demonstrate that clinical and genomic data are complementary sources of
      information relevant to survival, and we use the exploratory nature of the trees
      to identify potential genomic biomarkers worthy of further study.

PMID- 18618013
TI  - Androgen receptor-negative human prostate cancer cells induce osteogenesis in
      mice through FGF9-mediated mechanisms.
AB  - In prostate cancer, androgen blockade strategies are commonly used to treat
      osteoblastic bone metastases. However, responses to these therapies are typically
      brief, and the mechanism underlying androgen-independent progression is not
      clear. Here, we established what we believe to be the first human androgen
      receptor-negative prostate cancer xenografts whose cells induced an osteoblastic
      reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these
      cells grew in castrated as well as intact male mice. We identified FGF9 as being
      overexpressed in the xenografts relative to other bone-derived prostate cancer
      cells and discovered that FGF9 induced osteoblast proliferation and new bone
      formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody
      developed smaller bone tumors and reduced bone formation. Finally, we found
      positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors
      derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis
      cases studied. Collectively, these results suggest that FGF9 contributes to
      prostate cancer-induced new bone formation and may participate in the
      osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells
      may contribute to the castration-resistant osteoblastic progression of prostate
      cancer cells in bone and provide a preclinical model for studying therapies that
      target these cells.

PMID- 18618014
TI  - Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal
      transition during skin cancer formation and progression.
AB  - TGF-beta and its signaling mediators, Smad2, -3, and -4, are involved with tumor
      suppression and promotion functions. Smad4-/- mouse epidermis develops
      spontaneous skin squamous cell carcinomas (SCCs), and Smad3-/- mice are resistant
      to carcinogen-induced skin cancer; however, the role of Smad2 in skin
      carcinogenesis has not been explored. In the present study, we found that Smad2
      and Smad4, but not Smad3, were frequently lost in human SCCs. Mice with
      keratinocyte-specific Smad2 deletion exhibited accelerated formation and
      malignant progression of chemically induced skin tumors compared with WT mice.
      Consistent with the loss of Smad2 in poorly differentiated human SCCs, Smad2-/-
      tumors were poorly differentiated and underwent epithelial-mesenchymal transition
      (EMT) prior to spontaneous Smad4 loss. Reduced E-cadherin and activation of its
      transcriptional repressor Snail were also found in Smad2-/- mouse epidermis and
      occurred more frequently in Smad2-negative human SCCs than in Smad2-positive
      SCCs. Knocking down Snail abrogated Smad2 loss-associated EMT, suggesting that
      Snail upregulation is a major mediator of Smad2 loss-associated EMT. Furthermore,
      Smad2 loss led to a significant increase in Smad4 binding to the Snail promoter,
      and knocking down either Smad3 or Smad4 in keratinocytes abrogated Smad2 loss
      associated Snail overexpression. Our data suggest that enhanced Smad3/Smad4
      mediated Snail transcription contributed to Smad2 loss-associated EMT during skin
      carcinogenesis.

PMID- 18618015
TI  - APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create
      plasma cell niches in human mucosa.
AB  - The bone marrow constitutes a favorable environment for long-lived antibody
      secreting plasma cells, providing blood-circulating antibody. Plasma cells are
      also present in mucosa-associated lymphoid tissue (MALT) to mediate local
      frontline immunity, but how plasma cell survival there is regulated is not known.
      Here we report that a proliferation-inducing ligand (APRIL) promoted survival of
      human upper and lower MALT plasma cells by upregulating expression of the
      antiapoptotic proteins bcl-2, bcl-xL, and mcl-1. The in situ localization of
      APRIL was consistent with such a prosurvival role in MALT. In upper MALT,
      tonsillar epithelium produced APRIL. Upon infection, APRIL production increased
      considerably when APRIL-secreting neutrophils recruited from the blood
      infiltrated the crypt epithelium. Heparan sulfate proteoglycans (HSPGs) retained
      secreted APRIL in the subepithelium of the infected zone to create APRIL-rich
      niches, wherein IgG-producing plasma cells accumulated. In lower MALT,
      neutrophils were the unique source of APRIL, giving rise to similar niches for
      IgA-producing plasmocytes in villi of lamina propria. Furthermore, we found that
      mucosal humoral immunity in APRIL-deficient mice is less persistent than in WT
      mice. Hence, production of APRIL by inflammation-recruited neutrophils may create
      plasma cell niches in MALT to sustain a local antibody production.

PMID- 18618016
TI  - Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin
      resistance in rats.
AB  - Prolonged activation of p70 S6 kinase (S6K) by insulin and nutrients leads to
      inhibition of insulin signaling via negative feedback input to the signaling
      factor IRS-1. Systemic deletion of S6K protects against diet-induced obesity and
      enhances insulin sensitivity in mice. Herein, we present evidence suggesting that
      hypothalamic S6K activation is involved in the pathogenesis of diet-induced
      hepatic insulin resistance. Extending previous findings that insulin suppresses
      hepatic glucose production (HGP) partly via its effect in the hypothalamus, we
      report that this effect was blunted by short-term high-fat diet (HFD) feeding,
      with concomitant suppression of insulin signaling and activation of S6K in the
      mediobasal hypothalamus (MBH). Constitutive activation of S6K in the MBH mimicked
      the effect of the HFD in normal chow-fed animals, while suppression of S6K by
      overexpression of dominant-negative S6K or dominant-negative raptor in the MBH
      restored the ability of MBH insulin to suppress HGP after HFD feeding. These
      results suggest that activation of hypothalamic S6K contributes to hepatic
      insulin resistance in response to short-term nutrient excess.

PMID- 18618017
TI  - Sex differences in thrombosis in mice are mediated by sex-specific growth hormone
      secretion patterns.
AB  - Sex differences in thrombosis are well described, but their underlying
      mechanism(s) are not completely understood. Coagulation proteins are synthesized
      in the liver, and liver gene expression is sex specific and depends on sex
      differences in growth hormone (GH) secretion--males secrete GH in a pulsatile
      fashion, while females secrete GH continuously. Accordingly, we tested the
      hypothesis that sex-specific GH secretion patterns cause sex differences in
      thrombosis. Male mice were more susceptible to thrombosis than females in the
      thromboplastin-induced pulmonary embolism model and showed shorter clotting times
      ex vivo. GH-deficient little (lit) mice were protected from thrombosis, and
      pulsatile GH given to lit mice restored the male clotting phenotype. Moreover,
      pulsatile GH administration resulted in a male clotting phenotype in control
      female mice, while continuous GH caused a female clotting phenotype in control
      male mice. Expression of the coagulation inhibitors Proc, Serpinc1, Serpind1, and
      Serpina5 were strongly modulated by sex-specific GH patterns, and GH modulated
      resistance to activated protein C. These results reveal what we believe to be a
      novel mechanism whereby sex-specific GH patterns mediate sex differences in
      thrombosis through coordinated changes in the expression of coagulation inhibitor
      genes in the liver.

PMID- 18618019
TI  - statnet: Software Tools for the Representation, Visualization, Analysis and
      Simulation of Network Data.
AB  - statnet is a suite of software packages for statistical network analysis. The
      packages implement recent advances in network modeling based on exponential
      family random graph models (ERGM). The components of the package provide a
      comprehensive framework for ERGM-based network modeling, including tools for
      model estimation, model evaluation, model-based network simulation, and network
      visualization. This broad functionality is powered by a central Markov chain
      Monte Carlo (MCMC) algorithm. The coding is optimized for speed and robustness.

PMID- 18618018
TI  - Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through
      direct interactions with JAK2.
AB  - In addition to its role in megakaryocyte production, signaling initiated by
      thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia
      virus protooncogene (c-Mpl, or Mpl), controls HSC homeostasis and self-renewal.
      Under steady-state conditions, mice lacking the inhibitory adaptor protein Lnk
      harbor an expanded HSC pool with enhanced self-renewal. We found that HSCs from
      Lnk-/- mice have an increased quiescent fraction, decelerated cell cycle
      kinetics, and enhanced resistance to repeat treatments with cytoablative 5
      fluorouracil in vivo compared with WT HSCs. We further provide genetic evidence
      demonstrating that Lnk controls HSC quiescence and self-renewal, predominantly
      through Mpl. Consistent with this observation, Lnk-/- HSCs displayed potentiated
      activation of JAK2 specifically in response to TPO. Biochemical experiments
      revealed that Lnk directly binds to phosphorylated tyrosine residues in JAK2
      following TPO stimulation. Of note, the JAK2 V617F mutant, found at high
      frequencies in myeloproliferative diseases, retains the ability to bind Lnk.
      Therefore, we identified Lnk as a physiological negative regulator of JAK2 in
      stem cells and TPO/Mpl/JAK2/Lnk as a major regulatory pathway in controlling stem
      cell self-renewal and quiescence.

PMID- 18618021
TI  - Aligned Protein-Polymer Composite Fibers Enhance Nerve Regeneration: A Potential
      Tissue-Engineering Platform.
AB  - Sustained release of proteins from aligned polymeric fibers holds great potential
      in tissue-engineering applications. These protein-polymer composite fibers
      possess high surface-area-to-volume ratios for cell attachment, and can provide
      biochemical and topographic cues to enhance tissue regeneration. Aligned
      biodegradable polymeric fibers that encapsulate human glial cell-derived
      neurotrophic factor (GDNF, 0.13 wt%) were fabricated via electrospinning a
      copolymer of caprolactone and ethyl ethylene phosphate (PCLEEP) with GDNF. The
      protein was randomly dispersed throughout the polymer matrix in aggregate form,
      and released in a sustained manner for up to two months. The efficacy of these
      composite fibers was tested in a rat model for peripheral nerve-injury treatment.
      Rats were divided into four groups, receiving either empty PCLEEP tubes
      (control); tubes with plain PCLEEP electrospun fibers aligned longitudinally (EF
      L) or circumferentially (EF-C); or tubes with aligned GDNF-PCLEEP fibers (EF-L
      GDNF). After three months, bridging of a 15 mm critical defect gap by the
      regenerated nerve was observed in all the rats that received nerve conduits with
      electrospun fibers, as opposed to 50% in the control group. Electrophysiological
      recovery was seen in 20%, 33%, and 44% of the rats in the EF-C, EF-L, and EF-L
      GDNF groups respectively, whilst none was observed in the controls. This study
      has demonstrated that, without further modification, plain electrospun fibers can
      help in peripheral nerve regeneration; however, the synergistic effect of an
      encapsulated growth factor facilitated a more significant recovery. This study
      also demonstrated the novel use of electrospinning to incorporate biochemical and
      topographical cues into a single implant for in vivo tissue-engineering
      applications.

PMID- 18618020
TI  - Molecular evolution of Drosophila Cdc6, an essential DNA replication-licensing
      gene, suggests an adaptive choice of replication origins.
AB  - Increased size of eukaryotic genomes necessitated the use of multiple origins of
      DNA replication, and presumably selected for their efficient spacing to ensure
      rapid DNA replication. The sequence of these origins remains undetermined in
      metazoan genomes, leaving important questions about the selective constraints
      acting on replication origins unanswered. We have chosen to study the evolution
      of proteins that recognize and define these origins every cell cycle, as a
      surrogate to the direct analysis of replication origins. Among these DNA
      replication proteins is the essential Cdc6 protein, which acts to license origins
      for replication. We find that two different species pairs of Drosophila show
      evidence of positive selection in Cdc6 in their highly conserved C-terminal AAA
      ATPase domain. We also identified amino acid segments that are highly conserved
      in the N-terminal tail of Cdc6 proteins from various Drosophila species, but are
      not conserved even in closely related insect species. Instead, we find that the N
      terminal tails of Cdc6 proteins vary extensively in size and sequence across
      different eukaryotic lineages. Our results suggest that choice of origin firing
      may be significantly altered in closely related species, as each set of
      replication proteins optimizes to its own genomic landscape.

PMID- 18618022
TI  - Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11
      in mice.
AB  - Medial-to-intimal migration of SMCs is critical to atherosclerotic plaque
      formation and remodeling of injured arteries. Considerable amounts of the shed
      soluble form of the LDL receptor relative LR11 (sLR11) produced by intimal SMCs
      enhance SMC migration in vitro via upregulation of urokinase-type plasminogen
      activator receptor (uPAR) expression. Here, we show that circulating sLR11 is a
      novel marker of carotid intima-media thickness (IMT) and that targeted disruption
      of the LR11 gene greatly reduces intimal thickening of arteries through
      attenuation of Ang II-induced migration of SMCs. Serum concentrations of sLR11
      were positively correlated with IMT in dyslipidemic subjects, and multivariable
      regression analysis suggested sLR11 levels as an index of IMT, independent of
      classical atherosclerosis risk factors. In Lr11-/- mice, femoral artery intimal
      thickness after cuff placement was decreased, and Ang II-stimulated migration and
      attachment of SMCs from these mice were largely abolished. In isolated murine
      SMCs, sLR11 caused membrane ruffle formation via activation of focal adhesion
      kinase/ERK/Rac1 accompanied by complex formation between uPAR and integrin
      alphavbeta3, a process accelerated by Ang II. Overproduction of sLR11 decreased
      the sensitivity of Ang II-induced activation pathways to inhibition by an Ang II
      type 1 receptor blocker in mice. Thus, we demonstrate a requirement for sLR11 in
      Ang II-induced SMC migration and propose what we believe is a novel role for
      sLR11 as a biomarker of carotid IMT.

PMID- 18618023
TI  - Predictors of maternal language to infants during a picture book task in the
      home: Family SES, child characteristics and the parenting environment.
AB  - This study investigated the contribution of child characteristics and parenting
      environment to the relationship between family SES/demographic characteristics
      and maternal language to infants.1157 children were drawn from a representative
      sample of 1292 infants born to mothers in rural Appalachian counties and rural
      counties in southern minority U.S. communities. Mothers and their 6-8 month old
      babies were videotaped at home while talking about a wordless picture book.
      Mothers' language output and complexity were analyzed. Child temperament, age,
      and parenting environment (knowledge of child development and observed mother
      child engagement) were predictors of maternal language. Furthermore, their
      inclusion reduced the magnitude of the association between demographic
      characteristics and maternal language. Tests of mediation suggested that the
      parenting environment partially mediates the relationship between SES/demographic
      characteristics and maternal language. Findings are discussed with respect to
      identifying proximal processes that explain how SES may exert its influence on
      the language of young children.

PMID- 18618025
TI  - Water sorption and water solubility of current luting cements: an in vitro study.
AB  - OBJECTIVE: To evaluate the water-sorption characteristics and the solubility
      behavior of 4 luting cements-2 composite resins (CRs), a polyacid-modified
      composite resin (PMCR), and a resin-modified glass-ionomer cement (RMGIC)
      according to the ISO 4049 specifications. METHOD AND MATERIALS: Five disks (15 x
      1 mm) of each material (Variolink II [CR1; Vivadent], Panavia F [CR2; Kuraray],
      Resinomer [PMCR; Bisco], and Fuji Plus [RMGIC; GC]) were prepared according to
      the manufacturers' instructions. Specimens were first desiccated until a
      consistent mass was obtained. Specimens were immersed for 7 days in distilled
      water and immediately weighed after this period. Then the disks were post
      desiccated and weighed every day for 35 days. The water sorption and solubility
      of each specimen were calculated according to the change in its weight as
      observed before and after immersion and desiccation periods. RESULTS: Fuji Plus
      exhibited the overall higher values of water sorption and solubility (P < .001).
      Of the 3 resin-based luting cements, Resinomer demonstrated significantly higher
      water sorption and solubility (P < .001), whereas Variolink II and Panavia F
      showed low values and were not significantly different (P = .2). CONCLUSIONS:
      Behavior of resin-based materials in water varies according to the composition
      characteristics. In particular, the high portion of hydrophilic chemical species,
      as well as the filler characteristics, provoke very high water sorption and
      solubility values. In this way, and within the limitations of this in vitro
      study, composite resin luting cements appear to be more suitable than compomers
      and resin-modified glass-ionomer cements to meet longevity requirements.

PMID- 18618024
TI  - A single-step sequencing method for the identification of Mycobacterium
      tuberculosis complex species.
AB  - BACKGROUND: The Mycobacterium tuberculosis complex (MTC) comprises closely
      related species responsible for strictly human and zoonotic tuberculosis.
      Accurate species determination is useful for the identification of outbreaks and
      epidemiological links. Mycobacterium africanum and Mycobacterium canettii are
      typically restricted to Africa and M. bovis is a re-emerging pathogen.
      Identification of these species is difficult and expensive. METHODOLOGY/PRINCIPAL
      FINDINGS: The Exact Tandem Repeat D (ETR-D; alias Mycobacterial Interspersed
      Repetitive Unit 4) was sequenced in MTC species type strains and 110 clinical
      isolates, in parallel to reference polyphasic identification based on phenotype
      profiling and sequencing of pncA, oxyR, hsp65, gyrB genes and the major
      polymorphism tandem repeat. Inclusion of M. tuberculosis isolates in the
      expanding, antibiotic-resistant Beijing clone was determined by Rv0927c gene
      sequencing. The ETR-D (780-bp) sequence unambiguously identified MTC species type
      strain except M. pinnipedii and M. microti thanks to six single nucleotide
      polymorphisms, variable numbers (1-7 copies) of the tandem repeat and two
      deletions/insertions. The ETR-D sequencing agreed with phenotypic identification
      in 107/110 clinical isolates and with reference polyphasic molecular
      identification in all isolates, comprising 98 M. tuberculosis, 5 M. bovis BCG
      type, 5 M. canettii, and 2 M. africanum. For M. tuberculosis isolates, the ETR-D
      sequence was not significantly associated with the Beijing clone.
      CONCLUSIONS/SIGNIFICANCE: ETR-D sequencing allowed accurate, single-step
      identification of the MTC at the species level. It circumvented the current
      expensive, time-consuming polyphasic approach. It could be used to depict
      epidemiology of zoonotic and human tuberculosis, especially in African countries
      where several MTC species are emerging.

PMID- 18618026
TI  - Survey on hypodontia in Sayada, Tunisia.
AB  - OBJECTIVE: To determine dental agenesis prevalence in Sayada, Tunisia, a town
      from where many patients attend the Pediatric Department of Monastir University
      Dental School for such abnormalities, and to analyze its mode of inheritance.
      METHOD AND MATERIALS: A total of 262 schoolchildren in permanent dentition (134
      females and 128 males) aged 12 to 18 years (mean, 14.1 +/- 1.2 years) were
      examined to detect dental agenesis. In the case of a missing permanent tooth, a
      panoramic radiograph was taken to confirm diagnosis. A family survey
      questionnaire was completed for each case of multiple agenesis (at least 4 teeth
      missing). RESULTS: Findings revealed a dental agenesis prevalence of 13.3%.
      Altogether, 62 teeth were missing. No case of syndromal agenesis was detected;
      however, 12 children presented multiple agenesis (34.3%). The family survey was
      completed for only 9 of these subjects. CONCLUSION: Literature review showed a
      lower dental agenesis prevalence (3% to 7%) than did the present study. In the
      present study, females were more affected by this abnormality than males (16.4%
      and 10.3%, respectively). With the exception of third molars, the tooth most
      often missing was the mandibular second premolar (30.6%), followed by the
      maxillary second premolar (17.7%); hypodontia seemed to be symmetrical. Family
      surveys revealed a high rate of consanguinity in Sayada. Pedigree analysis of 9
      families showed that dental agenesis was probably related to an autosomal
      dominant inheritance.

PMID- 18618027
TI  - Resonance frequency analysis of long-term implant success in the posterior
      partially edentulous mandible.
AB  - OBJECTIVE: Resonance frequency analysis (RFA) has enabled the assessment of
      implant stability in terms of implant stability quotient (ISQ) units. This study
      evaluated the long-term stability of endosseous implants according to an ISQ
      scale of 1 to 100, as estimated by RFA in the posterior partially edentulous
      mandible. METHOD AND MATERIALS: A 2-stage procedure was used to place 328
      Braaemark implants in the edentulous mandibular molar region (second premolar to
      second molar) of 113 patients (49 men and 64 women). Patients were followed at
      regular intervals postoperatively, and ISQ scores were evaluated by RFA every
      year for 10 years. RESULTS: The implant success rate was 100%. ISQ scores did not
      significantly differ in the pattern of stability changes among different bone
      quantities and qualities during long-term follow-up. There was no significant
      difference in implant stability among the mandibular sides, the sites, and the
      sexes. CONCLUSION: Long-term stability of Branemark implants was excellent in the
      posterior partially edentulous mandible.

PMID- 18618028
TI  - Emergence angles in natural anterior teeth: influence on periodontal status.
AB  - OBJECTIVES: To find the geometric values of emergence angles in human natural
      anterior teeth and to study their influence on periodontal status. METHOD AND
      MATERIALS: Fifty anterior teeth with full-crown restorations and homologous
      contralateral sound teeth were examined for clinical parameters: Plaque Index,
      Gingival Index, probing depth, and clinical attachment loss. Impressions and
      stone casts were made and then separated along the midline of the teeth. All cut
      surface specimens were photocopied, scanned, and transferred into graphic form
      with a special program. The emergence angles of both restored and natural teeth
      were processed and recorded. Paired t test and multivariate linear regression
      analysis were used for statistical analysis. RESULTS: Mean supragingival
      emergence angles for facial and lingual surfaces of natural anterior teeth were
      11.13 +/- 7.92 and 15.58 +/- 9.16 degrees, respectively. The corresponding values
      for subgingival emergence angles were 9.93 +/- 5.68 and 14.35 +/- 8.44 degrees.
      The periodontal parameters were higher in restored teeth than in natural teeth.
      When Plaque Index and gender were controlled, a correlation was shown between the
      lingual subgingival emergence angle of the restored teeth and probing depth. A
      correlation was also found between the lingual supra- and subgingival emergence
      angles, as well as between both angles of the restored teeth and the attachment
      loss. CONCLUSION: The mean values of emergence angles obtained may aid clinicians
      and dental technicians in more easily designing the definitive emergence profile
      of restorations. The emergence profile of the restored teeth may affect
      periodontal status on the lingual aspect.

PMID- 18618029
TI  - Effect of airborne-particle abrasion on retentive strength in overtapered fixed
      prosthodontic restorations.
AB  - OBJECTIVE: To evaluate retentive strength and film thickness of complete metal
      crowns cemented to overtapered teeth with 3 different cements after the
      application of airborne-particle abrasion. METHOD AND MATERIALS: Sixty extracted
      maxillary molar teeth were embedded in autopolymerizing resin. Crowns were
      prepared with 30-degree overtapered axial walls and a 1-mm shoulder margin using
      a water-cooled cylindrical airborne-particle abrasion device. Then, 60 complete
      crowns were made from a nickel-chromium alloy. Teeth and crowns were assigned to
      2 groups, 30 to the control group and 30 to the experimental group to undergo
      airborne-particle abrasion. In the first part of study, 30 teeth from the
      experimental group were submitted to the silicon-replica technique and their
      buccolingual cross sections were measured so that cement film thickness could be
      measured before airborne-particle abrasion. Three measurements using a light
      microscope were made in 7 regions of each tooth. In the second part of study,
      complete metal crowns with and without airborne-particle abrasion were
      distributed into 3 groups with 10 teeth each to be cemented with zinc phosphate,
      polycarboxylate, or resin-modified glass ionomer. All specimens were subjected to
      a tensile bond test in an universal testing machine at a crosshead speed of 0.1
      mm/min until failure. The results were then evaluated with Student t test at a 5%
      level of significance. RESULTS: The film thickness showed no statistically
      significant differences among groups (P > .05). There was a significant
      difference between the control and experimental groups, with an increase in all 3
      cements after airborne-particle abrasion (P < .05). The highest retentive
      strength in the control group was found with resin-modified glass ionomer (141.4
      +/- 56.7 N), but there was no significant difference between the resin-modified
      glass ionomer (141.4 +/- 56.7 N) and zinc phosphate (121.4 +/- 24.2 N) (P > .05).
      Retentive strength of polycarboxylate was the lowest (78.03 +/- 16 N) (P < .05).
      For the experimental group, the difference among the zinc phosphate (220.5 +/-
      83.8 N), polycarboxylate (185.4 +/- 60.8 N), and resin-modified glass ionomer
      (228.9 +/- 62.4 N) was not statistically significant (P > .05). CONCLUSION:
      Airborne-particle abrasion had a positive effect on the retention of complete
      metal crowns when the crowns were cemented with zinc phosphate cement,
      polycarboxylate cement, or resin-modified glass-ionomer cement.

PMID- 18618030
TI  - The influence of different disinfectants on primary impression materials.
AB  - OBJECTIVE: To investigate the dimensional changes and the surface quality of
      dental impression materials after disinfection with 3 chemically different
      agents. METHOD AND MATERIALS: Four alginate impression materials and 1 addition
      silicone material were selected. The impressions were made from a brass model
      simulating a 3-unit fixed partial denture. The chemical disinfection was
      performed with 3 different disinfectants for 10 minutes. Three samples of each
      impression material and disinfectant agent were investigated. As a control, 3
      impressions of each material were made without any disinfection. The casts were
      made with a type IV dental stone. For each cast, 6 diameters and 3 distances were
      measured. To evaluate the dimensional stability, measurements were taken at a
      magnification of 34X with a light microscope. The surface quality was recorded
      using a profilometer. RESULTS: The dimensional change and surface quality
      differed minimally; however, statistically significant differences were found
      between alginate and addition silicone impression materials (ANOVA, P < .05).
      Casts from the silicone impressions were more accurate than the casts from
      alginate impressions. CONCLUSION: Different impression disinfection methods have
      only a marginal influence on dimensional stability and surface quality of dental
      casts. To achieve a higher precision, the use of an addition silicone can be
      recommended.

PMID- 18618031
TI  - Phenomenon of domination of the strongest contacts in centric occlusion.
AB  - OBJECTIVE: The number and distribution of occlusal contacts in centric occlusion
      (CO) and centric relation have been studied by a number of authors. All these
      studies have one thing in common--they define the greatest number of occlusal
      contacts between the molars. The purpose of the present study was to register the
      maximum clenching forces in CO, as well as to analyze the anatomic and functional
      factors that determine their localization on teeth. METHOD AND MATERIALS: The
      study included 42 subjects, aged 19 to 26 years, with intact dentition and Class
      I Angle occlusion; 38 persons had 1 to 4 restorations on the premolars and
      molars. The occlusal contacts were investigated in CO by the T-Scan system
      (Sentek) on wax and silicone impressions. The force loads in different sections
      of the dentition were differentiated by an additionally developed computer
      program. RESULTS: The T-Scan analysis and the developed computer program revealed
      that the maximum values of the clenching forces were recorded on the third
      molars. The strongest contacts found by the T-Scan system were successfully
      visualized in wax and silicone impressions. CONCLUSION: The maximum clenching
      forces of the masticatory muscles recorded by the T-Scan system were located in
      CO at the third molars in a dentition of 32 teeth and at the second molars in a
      dentition of 28 teeth. If the above-mentioned phenomenon is not taken into
      consideration in clinical practice, occlusal contacts may be created that will
      unfavorably transfer the specific clenching forces to a more medially located
      molar in cases of occlusal restoration of the same molar by a restoration or a
      single crown.

PMID- 18618032
TI  - The hidden axis.

PMID- 18618033
TI  - Bisphosphonate-related osteonecrosis of the jaws--report of 2 cases and
      strategies on prevention and management.
AB  - Two cases of bisphosphonate-related osteonecrosis of the jaws are reported-one in
      the maxilla and the other in the mandible. The patients were treated with long
      term antibiotics and minimal surgical debridement without major ablative surgery.
      Some clinical recommendations on prevention and management are suggested, as
      summarized from current literature.

PMID- 18618034
TI  - Subjective intensities of pain and contentment with treatment outcomes during
      tray bleaching of vital teeth employing different carbamide peroxide
      concentrations.
AB  - OBJECTIVES: It has been suggested that tooth whitening might cause considerable
      pain. The aim of this study was to evaluate subjective intensities of pain during
      bleaching of vital teeth and to assess the patients' contentment with the
      treatment outcome. METHOD AND MATERIALS: Thirty patients were treated for 1 week
      in a double-blind study design. Employing gels containing 17%, 10%, or 0%
      (control group) carbamide peroxide, patients wore bleaching trays for 2 hours per
      day and described subjective intensities of pain while wearing the trays by means
      of a visual analog scale. The patients' subjective contentment with the bleaching
      outcome was measured with an intermodal intensity comparison. RESULTS: For the
      17% gel, a median value of 3.5 U (max: 10; min: 1) for pain intensity was
      observed; this was statistically different from the value seen with the 10% group
      (2.0 U; max: 7; min: 0) (P < .05). Both test groups differed significantly from
      the control group, which had a median value of 0.0 U (max: 3; min: 0) (P < .05).
      Patients' contentment with the treatment outcome did not differ between the test
      groups (P > .05), although statistical differences were observed between the
      control and the test groups (P < .05) after bleaching for 1 week. CONCLUSION:
      Application of carbamide peroxide-containing bleaching agents to vital teeth
      causes pain correlated with the agent's concentration. Since both highly and less
      concentrated gels might result in a similar contentment with the treatment
      outcome, the use of highly concentrated agents appears not to be justified to
      improve vital tooth color.

PMID- 18618035
TI  - Implant therapy in aggressive periodontitis patients: a systematic review and
      clinical implications.
AB  - Implant therapy in partially edentulous patients has proven to be a predictable
      procedure with a high implant survival rate. The success rate in patients with a
      history of aggressive periodontitis, however, is still unclear. A Medline/PubMed
      search was conducted to identify and summarize articles published in English and
      reported on the survival of implants in aggressive, rapidly progressive, or
      juvenile periodontitis patients. Our search revealed only 9 articles, 4 of which
      were case reports. Although available evidence is weak, it suggests good short
      term survival of implants placed in periodontally well-maintained aggressive
      periodontitis patients. Bone loss around implants in aggressive periodontitis
      patients, however, appears to occur more frequently than it does in chronic
      periodontitis patients or periodontally healthy individuals. A summary and
      critical analysis of the aforementioned articles is presented.

PMID- 18618036
TI  - Toll-like receptors 2 and 4 gene polymorphisms in a Chinese population with
      periodontitis.
AB  - OBJECTIVES: Polymorphisms for toll-like receptor (TLR) 2 gene (Arg677Trp,
      Arg753Gln) and TLR4 gene (Asp299Gly, Thr399Ile) that are associated with impaired
      lipopolysaccharide (LPS) signal transduction have recently been described. The
      present study aimed to investigate the relationship between TLRs 2 and 4 gene
      polymorphisms and periodontitis in a Chinese population. METHOD AND MATERIALS:
      Forty patients with generalized aggressive periodontitis, 50 patients with
      chronic periodontitis, and 100 periodontally healthy controls were recruited. All
      these subjects were of Han Chinese ethnicity. Genomic DNA was extracted from
      whole-blood samples. TLRs 2 and 4 genes were analyzed by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) with respective
      restriction endonucleases. The alleles were detected by polyacrylamide gel
      electrophoresis and visualized with ethidium bromide. RESULTS: Heterozygosity for
      the TLR2 Arg677Trp polymorphism was found in all subjects. The TLR2 Arg753Gln
      mutant allele was not found in periodontitis patients, while a heterozygous
      frequency of 6% (6 of 100) was detected in the controls. The TLR4 Asp299Gly and
      Thr399Ile mutant alleles were not found in any of the subjects. CONCLUSION: TLR2
      Arg753Gln polymorphism may not be associated with aggressive or chronic
      periodontitis in the Chinese population. The prevalence of TLR2 Arp677Trp
      polymorphism seemed to be rather high, while that of TLR4 Asp299Gly and Thr399Ile
      polymorphisms seemed to be rather low in the Chinese population, which did not
      permit any conclusion regarding its effects on periodontitis.

PMID- 18618037
TI  - Multiple sinus tracts as a result of root fracture: a case report.
AB  - Sinus tracts are a consequence of chronic apical disease or vertical root
      fractures. They are usually diagnosed upon routine clinical examination or in
      response to patient complaints of swelling and occasional pus secretion. An
      unusual case report of a maxillary canine with multiple orifices of sinus tracts
      is presented. Vertical root fracture was confirmed after removal of the root
      canal filling under an operating microscope. Clinicians should suspect vertical
      root fracture when multiple sinus tracts originating from the same tooth are
      observed.

PMID- 18618038
TI  - The disinfecting effect of ozonized oxygen in an infected root canal: an in vitro
      study.
AB  - OBJECTIVES: To determine the disinfecting effect of ozonized oxygen (120 seconds
      from the HealOzone generator, KaVo) on Enterococcus faecalis, representing
      bacteria that are difficult to eliminate in the root canals of human teeth, and
      to compare it with the conventional irrigants: sterile physiologic sodium
      chloride solution (negative control group), 3% hydrogen peroxide solution, 0.2%
      chlorhexidine solution, 1.5% sodium hypochlorite solution, and 3% sodium
      hypochlorite solution (positive control group). METHOD AND MATERIALS: The roots
      (n = 10 in each group) were sterilized, contaminated with the test microorganisms
      in a quantitative preparation, rinsed with the test solutions, and dried. The
      residual concentration of E faecalis was determined through another irrigation
      stage with the sodium chloride solution. RESULTS: The positive control group
      showed a significantly lower concentration of microorganisms than all the other
      groups, whereas the negative control group showed a significantly higher
      concentration compared to the other groups. The test groups showed low
      concentrations. CONCLUSION: Ozonized oxygen appears to be suitable for
      disinfecting root canal systems in cases where sodium hypochlorite is not
      indicated.

PMID- 18618039
TI  - An evaluation of bacterial contamination of barriers used in periapical tissue
      regeneration: Part 2--Bacterial penetration.
AB  - OBJECTIVE: To compare the relative penetration of Prevotella melaninogenica and
      Enterococcus faecalis through 3 guided tissue regeneration membranes: Atrisorb,
      Lambone, and OsseoQuest. It was hypothesized that OsseoQuest would show increased
      bacterial penetration when compared to Lambone and Atrisorb. METHOD AND
      MATERIALS: Centrifuge tubes containing trypticase soy broth were sealed with
      circular sections of membranes and placed in test tubes containing culture media.
      The bacterial penetration was assessed by passage of bacteria from the outer tube
      culture media to the inner centrifuge tube media through the membrane. After
      incubation for 4 and 48 hours, the media from the outer and inner tubes were
      compared for bacterial count. RESULTS: P melaninogenica exhibited 91% penetration
      for Lambone in 2 days, while OsseoQuest displayed 87% penetration with E faecalis
      in the same time. Atrisorb displayed a minimal penetration with both bacteria
      (2%). CONCLUSION: Atrisorb displayed the least bacterial penetration, which may
      be attributed to membrane structure, chemical configuration, hydrophobicity, and
      porosity of tested membranes.

PMID- 18618040
TI  - Effect of different photoactivation methods on the bond strength of composite
      resin restorations by push-out test.
AB  - OBJECTIVE: Modulated curing methods could lead to a higher probability of bond
      preservation. Therefore, the aim of this study was to evaluate the effect of 7
      curing methods on bond strength of composite resin restorations. METHOD AND
      MATERIALS: Seventy bovine incisors were selected. A conical cavity was prepared
      in the buccal surface. Adper Single Bond adhesive system was applied according to
      the manufacturer's instructions, and the cavities were filled with a single
      increment of Esthet X (Dentsply/Caulk). The specimens were randomly assigned into
      7 groups (n = 10) according to the photoactivation method: (1) continuous light
      700 (700 mW/cm2) (control); (2) continuous light 150 (150 mW/cm2); (3) continuous
      light 250 (250 mW/cm2); (4) soft-start 75 (75 mW/cm2) + 700 mW/cm2); (5) soft
      start 150 (150 mW/cm2 + 700 mW/cm2); (6) pulse-delay (150 mW/cm2 + 3 minutes +
      700 mW/cm2); and (7) intermittent light (cycles at 600 mW/cm2). The energy
      density for all groups was 14 J/cm2. The bond strength of the composite
      restorations was measured by performing the push-out test in a universal testing
      machine (Instron). The results were submitted to ANOVA and Tukey test (P < .05).
      RESULTS: Pulse-delay, soft-start 150, and soft-start 75 methods showed a
      significant increase in bond strength when compared with the control continuous
      light 700 method. Low power density and intermittent light groups showed
      intermediate results. CONCLUSION: Modulation of the energy density during light
      curing of composite resins using pulse-delay or soft-start methods increased the
      bond strength of composite restorations.

PMID- 18618041
TI  - Odontogenic keratocyst and multiple supernumerary teeth in a patient with Ehlers
      Danlos syndrome--a case report and review of the literature.
AB  - Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue
      related to collagen metabolism. Deficiency or alteration of the collagen present
      in the tissues results in some classic signs such as skin hyperelasticity,
      articular hypermobility, and vascular fragility, among others. In addition, EDS
      oral manifestations are rarely cited in the literature. The aim of this article
      is to report a rare case of a young female patient with EDS who presented
      supernumerary teeth and an odontogenic keratocyst. There is no report in the
      literature of the simultaneous occurrence of these alterations. The article
      further highlights the importance of EDS diagnosis in patients who need dental
      treatment and the due care for their assistance.

PMID- 18618042
TI  - Dentinogenesis imperfecta: the importance of early treatment.
AB  - Dentinogenesis imperfecta, also known as hereditary opalescent dentin, is a
      dentin development disorder with autosomal dominant transmission that affects
      both the primary and permanent dentition. A case is reported of a family in which
      the mother and her 6- and 20-year-old children were diagnosed with dentinogenesis
      imperfecta type II. The mouths of these patients illustrate the progressive
      deterioration of affected teeth if not adequately treated. The treatment of the 6
      year-old son is described, and therapeutic approaches to this disorder in primary
      and permanent dentition are reviewed. This family exemplifies the need for the
      earliest possible diagnosis and treatment of dentinogenesis imperfecta to prevent
      extensive deterioration of the dentition and occlusion.

PMID- 18618043
TI  - [Evaluation of medical performance in the hospital activity].

PMID- 18618044
TI  - [Our iceberg is melting. Part 2].

PMID- 18618045
TI  - [Mitral valve replacement in patiens with previous right pneumonectomy].
AB  - Adequate exposure of the mitral valve is essential to the safe and effective
      performance of valve replacement. After a right pneumonectomy, shift of the
      mediastinum and reduction in respiratory function makes cardiac surgery
      challenging not only for the surgeon but also for the anaesthetist. We report our
      experience on performing mitral valve replacement in two patients with previous
      right pneumonectomy to highlight certain important features while managing these
      patients.

PMID- 18618046
TI  - [Surgery of pulmonary metastasis].
AB  - Between April 1993 and December 2007, 92 patients underwent the complete
      resection of pulmonary metastases, 47 mens (51.1%) and 45 womens (49.9%). 26
      patients (27.2%) had solitary pulmonary metastasis, 25 (26.1%) multiple pulmonary
      metastasis and 41 (44.5%) patients presented bilateral pulmonary metastasis. 42
      patients (45.6%) presented pulmonary metastasis recurrence, 14 patients (15.2%) a
      second recurrence and 6 patients (6.5%) a third pulmonary metastasis recurrence.
      49 patients (53.2%) were reoperated. The mean cumulative survival after complete
      resection was 78.4 months (+/- 52.5 months). There were no operative mortality.
      CONCLUSION: Thys work demonstrated that every attempt should be made to
      completely ressect all clinically detected metastases. Complete resection of
      pulmonary metastasis, even in recurrent disease is compatible with long-term
      survival.

PMID- 18618047
TI  - [Sleeve lobectomy for bronchial carcinoid tumour: two case reports].
AB  - The authors report two cases of patients with typical carcinoid-tumour who
      underwent rigid bronchoscopy and Nd:YAD laser photocoagulation with posterior
      surgical resection (sleeve lobectomy). Clinical presentation, investigation and
      treatment of this kind of tumours are described.

PMID- 18618049
TI  - [Buerger's disease: current concepts].
AB  - Buerger's disease or thromboangiitis obliterans is a non atherosclerotic,
      segmentar inflammatory vasculitis that reaches small and medium size vessels of
      the limbs's extremities. It affects predominantly young male smokers that present
      distal ischemia, clinically manifested through claudication, rest pain, ulcers
      and gangrene. A hundred years after its original description by Leo Buerger, the
      disease's etiology remains unclear, but it is acknowledged the importance of
      tobacco's role for the initiation, progression and prognosis of the pathology.
      Its incidence has globally declined, despite the relative increment of female
      cases owing to the crescent number of smoking women. The treatment has suffered a
      considerable evolution, manifested by the decreasing number of performed
      amputations, but it should always be followed by complete interruption of the
      smoking habits - the central attitude of the therapeutics. The introduction of
      the antagonists of cannabinoid like rimonabant, revealed promising in helping
      pacients stop smoking. Prostanoids are nowadays an important therapeutic
      attitude. Sympathectomy and omental transfer are included as surgical therapeutic
      options. The recent evolution in the discovery of new therapeutic resources in
      the angiogenesis scope, have opened up new possibilities for the treatment of
      Buerger's disease, considered one of the least treatable vasculitis.

PMID- 18618048
TI  - [The unknown history of heparin's discovery].
AB  - Heparin was accidentally discovered in 1916 by Jay McLean, a second-year medical
      student working at the Department of Physiology of the Johns Hopkins Medical
      School in Baltimore, under the direction of the eminent scientist William Howell.
      The discovery of heparin was not followed by immediate practical use and only
      twenty years later was recognized its clinical utility in the treatment of post
      traumatic venous thrombosis of the lower extremities, by the canadians Charles
      Best and Gordon Murray. Jay McLean expired in 1957, dismayed and depressed with
      the indiference devoted by the scientific community to its discovery and only
      several years later the fact was recognized in a simple ceremony to testify its
      participation in the discovery of a drug that promoted the progress and
      development of vascular and cardiac surgery, the extracorporeal circulation, the
      haemodialysis, the organ transplantation and the treatment and prevention of
      arterial and venous thromboembolism.

PMID- 18618050
TI  - [Reconstructive surgery of an upper abdominal aortic coarctation, associated to
      bilateral renal artery aneurysms. Case report].
AB  - The authors report the clinical case of a 13 year old girl with the diagnosis of
      arterial hypertension, consequence of an upper abdominal aortic coarctation,
      involving the origin of both renal arteries and the superior mesenteric artery.
      Surgical exploration disclosed the coexistence of displasic aneurysms at the
      origin of both renal arteries. She underwent a complex revascularization
      procedure, which is described, and the post operative course was uneventfull,
      having normalised the values of the blood pressure. The main features of
      etiopathogeny, clinical presentation, diagnosis and surgical management of this
      entity are discussed, based on an extensive review of the literature.

PMID- 18618051
TI  - [Chronic venous disorders and chronic venous diseases: concepts and evaluation].
AB  - The field of chronic venous disorders suffered, in the past, from lack of
      precision in diagnosis and classification. These deficiencies led to conflicting
      reports in studies of management of specific venous problems. To solve these
      troubles, the CEAP classification for chronic venous disorders was created in
      1994, and was incorporated into the International Reporting Standard in Venous
      Disorders, in 1995. Actually it is generally accepted and used. In 2004 an "ad
      hoc" committee of the American Venous Forum working with an international liaison
      committee, has recommended a number of practical changes, that include a
      refinement of several definitions used in describing these disorders and a
      simpler alternative to the full (advanced) CEAP classification, the so called
      basic CEAP version. The author presents a revision of this document and adapts
      the nomenclature used to the portuguese language. He gives special attention to
      the fact that CEAP classification is a descriptive one which is associated to a
      venous severity and a quality of life scores that are instruments for
      longitudinal research to assess outcomes. Finally the author advises to use of
      these scores specially when it is necessary to evaluate the outcomes of the
      treatment with veno- active drugs.

PMID- 18618052
TI  - [Splenic infarction caused by supra-celiac aortic thrombus. Two case reports].
AB  - Aortic mural thrombosis is a rare situation in clinical practice. Its pathogeny
      is ignored in the majority of cases and clinical presentation is variable,
      according to the location of the thrombus and the multiple and diverse forms of
      embolism that can cause. For these reasons, clinical diagnosis may be extremally
      difficult. The authors report the cases of two women aged 52 and 41 years old
      respectivelly admitted in the Emergency Department with abdominal and lumbar
      pain, due splenic embolic infarctions, a diagnosis made by CT-Scans. The computed
      tomography disclosed also the presence of mural thrombus in the celiac aorta, one
      of them as a floating thrombus, which were regarded as the source of the
      embolism. Supraceliac aortic thrombectomy was performed, associated to
      splenectomy in both cases. Post operative course was uneventfull and reviewed 10
      months and 9 years after the operation, they were found in pretty good condition,
      with no evidence of recurrence of the disease.

PMID- 18618053
TI  - [Post traumatic pseudo-aneurysm of the popliteal artery with late clinical
      presentation].

PMID- 18618054
TI  - To kill a mocking bird flu?

PMID- 18618055
TI  - Clinical and epidemiological features of patients with confirmed avian influenza
      presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007.
AB  - INTRODUCTION: Since the first human cases of H5N1 avian influenza virus infection
      were detected in Indonesia in 2005, the Sulianti Saroso Infectious Diseases
      Hospital in Jakarta has managed 27 confirmed cases from September 2005 to
      December 2007. MATERIALS AND METHODS: We reviewed the clinical and
      epidemiological data of these patients. RESULTS: Clinical and radiological
      features were not specific. Most patients were young and had indirect contact
      with infected poultry. The majority of cases presented to the Infectious Diseases
      hospital late when the patients already had features of the systemic inflammatory
      response syndrome (SIRS). The mortality was high at 77%. CONCLUSION: There is
      clearly an urgent need for better field diagnostics and therapeutics for the
      management of this emerging pathogen.

PMID- 18618056
TI  - A cross-sectional study of primary-care physicians in Singapore on their concerns
      and preparedness for an avian influenza outbreak.
AB  - INTRODUCTION: During an avian influenza (AI) pandemic, primary-care physicians
      (PCPs) are expected to play key roles in the prevention and control of the
      disease. Different groups of PCPs could have different concerns and preparedness
      level. We assessed the concerns, perceived impact and preparedness for an
      outbreak among PCPs in Singapore. MATERIALS AND METHODS: A cross-sectional survey
      of PCPs working in private practice (n=200) and public clinics (n=205) from March
      to June 2006 with an anonymous self-administered questionnaire on concerns (12-
      items), perceived impact (10 items) and preparedness (10 items) for an outbreak.
      RESULTS: Two hundred and eighty-five PCPs responded - 149 (response rate: 72.7%)
      public and 136 (response rate: 67.3%) private. The majority were concerned about
      risk to their health from their occupation (95.0%) and falling ill with AI
      (89.7%). Most (82.5%) accepted the risk and only 33 (11.8%) would consider
      stopping work. For perceived impact, most felt that people would avoid them
      (69.6%) and their families (54.1%). The majority (81.3%) expected an increased
      workload and feeling more stressed at work (86.9%). For preparedness, 78.7% felt
      personally prepared for an outbreak. Public PCPs were more likely to be involved
      in infection-control activities and felt that their workplaces were prepared.
      CONCLUSIONS: Most PCPs felt personally prepared for an outbreak but were
      concerned about their exposure to AI and falling ill. Other concerns included
      social ostracism for themselves and their families. Public PCPs appeared to have
      a higher level of preparation. Addressing concerns and improving level of
      preparedness are crucial to strengthen the primary-care response for any AI
      outbreak.

PMID- 18618057
TI  - The efficacy of influenza vaccination in healthcare workers in a tropical
      setting: a prospective investigator blinded observational study.
AB  - INTRODUCTION: Influenza vaccine has been shown to be highly effective in
      temperate regions with well-defined seasonal influenza. Healthcare workers (HCWs)
      are advised to receive regular influenza vaccination to protect themselves and
      their patients. However, there are limited data on the efficacy of influenza
      vaccine in HCWs in the tropics. MATERIALS AND METHODS: In this observational,
      investigator blinded cohort study, bi-monthly questionnaires recording influenza
      like illness (ILI) episodes and medical leave were administered to 541 HCWs at
      the Singapore National University Hospital and KK Women's and Children's Hospital
      from 2004 to 2005. ILI was defined according to a standard symptom score.
      RESULTS: Baseline characteristics were comparable in both the vaccinated and non
      vaccinated groups. Overall, the relative risk of self-reported ILI in vaccinated
      HCWs was 1.13 [95% confidence interval (CI), 0.98-1.13; P=0.107]; medical leave
      taken was lower in the vaccinated group [mean 0.26+/-0.6 days per visit, compared
      with 0.30+/-0.5 days in the non-vaccinated group (P=0.40)]. Because of the
      reported Northern Hemisphere 2003/04 vaccine mismatch, we stratified the cohort
      and determined that the group which received a matched vaccine had a relative
      risk of ILI of 0.49 (95% CI, 0.37-0.66; P<0.001), achieving a vaccine efficacy of
      51%. Mean medical leave decreased significantly in HCWs who received the matched
      vaccine, compared with those who did not receive vaccination (0.13+/-0.3 vs
      0.30+/-0.5; P<0.001) and with HCWs vaccinated with mismatched strains (0.13+/-0.3
      vs 0.39+/-0.9; P=0.01). CONCLUSIONS: A well-matched influenza vaccine is
      effective in preventing ILI and reducing sickness absence in healthcare workers
      in tropical settings. Efforts need to be made to increase influenza vaccination
      rates and to improve the currently available vaccines.

PMID- 18618058
TI  - Twentieth century influenza pandemics in Singapore.
AB  - INTRODUCTION: Singapore was substantially affected by three 20th Century
      pandemics. This study describes the course of the pandemics, and the preventive
      measures adopted. MATERIALS AND METHODS: We reviewed and researched a wide range
      of material including peer-reviewed journal articles, Ministry of Health reports,
      Straits Settlements reports and newspaper articles. Monthly mortality data were
      obtained from various official sources in Singapore. RESULTS: The 1918 epidemic
      in Singapore occurred in 2 waves--June to July, and October to November-
      resulting in up to 3500 deaths. The 1957 epidemic occurred in May, and resulted
      in widespread morbidity, with 77,000 outpatient attendances in government clinics
      alone. The 1968 epidemic occurred in August and lasted a few weeks, with
      outpatient attendances increasing by more than 65%. The preventive measures
      instituted by the Singapore government during the pandemics included the closure
      of schools, promulgation of public health messages, setting up of influenza
      treatment centres, and screening at ports. Students, businessmen and healthcare
      workers were all severely affected by the pandemics. CONCLUSIONS: Tropical cities
      should be prepared in case of a future pandemic. Some of the preventive measures
      used in previous pandemics may be applicable during the next pandemic.

PMID- 18618059
TI  - A global perspective on avian influenza.
AB  - Global public health security is both a collective aspiration and a mutual
      responsibility that demands cooperative action at all levels. The expansion of
      the current H5N1 avian influenza enzootic and its incursion into human health
      presents a real and significant threat of an influenza pandemic. The world has
      for the first time an unprecedented opportunity for pandemic preparation. Current
      global efforts to tackle the H5N1 pandemic threat are centred around the
      framework of the International Health Regulations (2005) that requires countries
      to openly share disease intelligence including clinical samples, viruses and
      epidemiological information. Present international initiatives also seek to
      establish more equitable allocation and sharing mechanisms for developing
      countries, of therapeutic resources, public health interventions and other broad
      based support in the event of a pandemic. To be sustainable, country preparatory
      efforts need to be integrated within wider national emergency preparedness
      frameworks and emphasise the strengthening of basic capacities in disease
      surveillance, outbreak response and health systems that can respond to a range of
      public health emergencies. Such capacity building represents permanent
      investments in health that will have enduring benefits beyond a pandemic.
      Preparations must also go beyond the health sector; greater promotion of
      intersectoral cooperation and an adoption of a whole-of-society approach to
      preparation is recommended. Broad collaboration is vital in addressing the
      complex challenge posed by influenza to our collective security.

PMID- 18618060
TI  - Towards mutual trust, transparency and equity in virus sharing mechanism: the
      avian influenza case of Indonesia.
AB  - INTRODUCTION: As the country hardest hit by avian influenza, both in poultry and
      in human, Indonesia's decision to withhold samples of avian influenza virus A
      (H5N1) has fired up a global controversy. The objective of this paper is to
      describe the position taken by Indonesia in the events leading to the decision
      and in those conducted to resolve the situation. METHODS: The sources for this
      paper are the Indonesian human influenza A(H5N1) case reports and study results,
      summaries, minutes and reports of national and international meetings of virus
      sharing, and other related Indonesian and WHO documents. RESULTS: The
      International Health Regulations 2005 have been applied in different ways based
      on different interpretations. While one party insists on the importance of free,
      non-conditional, virus sharing for risk assessment and risk response, Indonesia-
      as supported by most of the developing countries--stresses on the more basic
      principles such as sovereignty of a country over its biological materials,
      transparency of the global system, and equity between developed and developing
      nations. CONCLUSIONS: This event demonstrates the unresolved imbalance between
      the affluent high-tech countries and the poor agriculture-based countries.
      Regional, global and in-country meetings must continue to be conducted to find
      solutions acceptable to all.

PMID- 18618061
TI  - Avian influenza and pandemic influenza preparedness in Hong Kong.
AB  - Avian influenza A H5N1 continues to be a major threat to global public health as
      it is a likely candidate for the next influenza pandemic. To protect public
      health and avert potential disruption to the economy, the Hong Kong Special
      Administrative Region Government has committed substantial effort in preparedness
      for avian and pandemic influenza. Public health infrastructures for emerging
      infectious diseases have been developed to enhance command, control and
      coordination of emergency response. Strategies against avian and pandemic
      influenza are formulated to reduce opportunities for human infection, detect
      pandemic influenza timely, and enhance emergency preparedness and response
      capacity. Key components of the pandemic response include strengthening disease
      surveillance systems, updating legislation on infectious disease prevention and
      control, enhancing traveller health measures, building surge capacity,
      maintaining adequate pharmaceutical stockpiles, and ensuring business continuity
      during crisis. Challenges from avian and pandemic influenza are not to be
      underestimated. Implementing quarantine and social distancing measures to contain
      or mitigate the spread of pandemic influenza is problematic in a highly urbanised
      city like Hong Kong as they involved complex operational and ethical issues.
      Sustaining effective risk communication campaigns during interpandemic times is
      another challenge. Being a member of the global village, Hong Kong is committed
      to contributing its share of efforts and collaborating with health authorities
      internationally in combating our common public health enemy.

PMID- 18618062
TI  - Preparing for an influenza pandemic in Singapore.
AB  - The national strategy against pandemic influenza essentially consists of 3
      prongs: (i) effective surveillance, (ii) mitigation of the pandemic's impact, and
      (iii) render the population immune through vaccination. When the pandemic hits
      Singapore, the response plan aims to achieve the following 3 outcomes: (i)
      maintenance of essential services to limit social and economic disruption, (ii)
      reduction of morbidity and mortality through antiviral treatment, and (iii) slow
      and limit the spread of influenza to reduce the surge on healthcare services. The
      biggest challenge will come from managing the surge of demand on healthcare
      services. A high level of preparedness will help healthcare services better cope
      with the surge.

PMID- 18618063
TI  - Prevention and control of avian influenza in Singapore.
AB  - The highly pathogenic avian influenza (HPAI) H5N1 virus was first detected in
      1996 in Guangdong, China. Since 2003, H5N1 outbreaks have been reported in parts
      of Asia, Europe, the Middle East, and Africa. It is currently entrenched among
      poultry in parts of Asia and poses a major challenge to animal and human health.
      Singapore is free from HPAI. Given Singapore's need to import food, the Agri-Food
      and Veterinary Authority (AVA) has adopted a pro-active risk management system to
      prevent the introduction of HPAI. AVA's approach maybe described as a multi
      layered control strategy for the prevention and control of HPAI. The strategy
      includes control measures at source, border control measures, local control
      measures and emergency preparedness.

PMID- 18618064
TI  - Vaccines for pandemic influenza. The history of our current vaccines, their
      limitations and the requirements to deal with a pandemic threat.
AB  - Fears of a potential pandemic due to A(H5N1) viruses have focussed new attention
      on our current vaccines, their shortcomings, and concerns regarding global
      vaccine supply in a pandemic. The bulk of current vaccines are inactivated split
      virus vaccines produced from egg-grown virus and have only modest improvements
      compared with those first introduced over 60 years ago. Splitting, which was
      introduced some years ago to reduce reactogenicity, also reduces the
      immunogenicity of vaccines in immunologically naive recipients. The A(H5N1)
      viruses have been found poorly immunogenic and present other challenges for
      vaccine producers which further exacerbate an already limited global production
      capacity. There have been some recent improvements in vaccine production methods
      and improvements to immunogenicity by the development of new adjuvants, however,
      these still fall short of providing timely supplies of vaccine for all in the
      face of a pandemic. New approaches to influenza vaccines which might fulfil the
      demands of a pandemic situation are under evaluation, however, these remain some
      distance from clinical reality and face significant regulatory hurdles.

PMID- 18618065
TI  - Antiviral drugs for the control of pandemic influenza virus.
AB  - In the advent of an influenza virus pandemic it is likely that the administration
      of antiviral drugs will be an important first line of defence against the virus.
      The drugs currently in use are effective against seasonal influenza virus
      infection, and some cases have been used in the treatment of patients infected
      with the avian H5N1 influenza virus. However, it is becoming clear that the
      emergence of drug-resistant viruses will potentially be a major problem in the
      future efforts to control influenza virus infection. In addition, during a new
      pandemic, sufficient quantities of these agents will need to be distributed to
      many different parts of the world, possibly at short notice. In this review we
      provide an overview of some of the drugs that are currently available for the
      treatment and prevention of influenza virus infection. In addition, basic
      research on influenza virus is providing a much better understanding of the
      biology of the virus, which is offering the possibility of new anti-influenza
      virus drugs. We therefore also review some new antiviral strategies that are
      being reported in the scientific literature, which may form the basis of the next
      generation of antiviral strategies during a future influenza virus pandemic.

PMID- 18618066
TI  - Risk communications: in search of a pandemic.
AB  - This paper explores the difficulties in managing risk communications in the face
      of uncertainty of an avian flu pandemic over a protracted period. The
      communications effort has also been made more difficult by the confusion and
      cacophony in the media and claims by experts and politicians worldwide. While
      Singapore secured much praise for its handling of the severe acute respiratory
      syndrome (SARS) just 4 years earlier which threatened its very existence as a
      nation-state, it also had to "unlearn" and "unfix" assumptions and mindsets that
      grew out of that experience. A protracted crisis of uncertainty has also raised
      difficult questions of sustaining public awareness and alertness. Compounding
      these problems is the seemingly high reliance of Singaporeans on Government to
      manage the crisis at all stages. Risk communications has become a crucial
      necessity in an increasingly troubled world and evokes contradictions for many in
      medicine and public health - calling on Governments to raise the alarm whilst
      also calming fears at the same time. It is hoped that Singapore's experience
      throws up some useful lessons for other countries. The basic principles of risk
      communications employed are in line with the best practices adopted by many other
      countries. The experience may also contribute to the ongoing and somewhat
      contentious debate on whether the manner in which Singapore manages the
      information flow can be replicated or applied by other states and cultures.

PMID- 18618067
TI  - Frequency and pattern of heteroplasmy in the control region of human
      mitochondrial DNA.
AB  - In this work, we present the results of the screening of human mitochondrial DNA
      (mtDNA) heteroplasmy in the control region of mtDNA from 210 unrelated Spanish
      individuals. Both hypervariable regions of mtDNA were amplified and sequenced in
      order to identify and quantify point and length heteroplasmy. Of the 210
      individuals analyzed, 30% were fully homoplasmic and the remaining presented
      point and/or length heteroplasmy. The prevalent form of heteroplasmy was length
      heteroplasmy in the poly(C) tract of the hypervariable region II (HVRII),
      followed by length heteroplasmy in the poly(C) tract of hypervariable region I
      (HVRI) and, finally, point heteroplasmy, which was found in 3.81% of the
      individuals analyzed. Moreover, no significant differences were found in the
      proportions of the different kinds of heteroplasmy in the population when blood
      and buccal cell samples were compared. The pattern of heteroplasmy in HVRI and
      HVRII presents important differences. Moreover, the mutational profile in
      heteroplasmy seems to be different from the mutational pattern detected in
      population. The results suggest that a considerable number of mutations and,
      particularly, transitions that appear in heteroplasmy are probably eliminated by
      drift and/or by selection acting at different mtDNA levels of organization.
      Taking as a whole the results reported in this work, it is mandatory to perform a
      broad-scale screening of heteroplasmy to better establish the heteroplasmy
      profile which would be important for medical, evolutionary, and forensic
      proposes.

PMID- 18618068
TI  - Genetic diversity of Pto-like serine/threonine kinase disease resistance genes in
      cultivated and wild strawberries.
AB  - Degenerate oligonucleotide primers, designed based on conserved regions of
      several serine-threonine kinases (STK) previously cloned in tomato and
      Arabidopsis, were used to isolate STK candidates in wild and cultivated
      strawberries. Seven distinct classes of STKs were identified from three related
      wild species, i.e., Fragaria vesca, Fragaria chiloensis, and Potentilla
      tucumanensis, and seven different Fragaria x ananassa cultivars. Alignment of the
      deduced amino acid sequences and the Pto R protein from tomato revealed the
      presence of characteristic subdomains and conservation of the plant STK consensus
      and other residues that are crucial for Pto function. Based on identity scores
      and clustering in phylogenetic trees, five groups were recognized as Pto-like
      kinases. Strawberry Pto-like clones presented sequences that were clearly
      identified as the activation segments contained in the Pto, and some of them
      showed residues previously identified as being required for binding to AvrPto.
      Some of the non-Pto-like kinases presented a high degree of identity and grouped
      together with B-lectin receptor kinases that are also involved in disease
      resistance. Statistical studies carried out to evaluate departure from the
      neutral theory and nonsynonymous/synonymous substitutions suggest that the
      evolution of STK-encoding sequences in strawberries is subjected mainly to a
      purifying selection process. These results represent the first report of Pto-like
      STKs in strawberry.

PMID- 18618069
TI  - The AdLMP-1 transfection in two different cells; AF cells, chondrocytes as
      potential cell therapy candidates for disc degeneration.
AB  - BACKGROUND: LMP-1 is known to increase proteoglycan production through the
      upregulating the BMPs and it is also known that BMP-2 acts on anulus fibrosus
      cells and chondrocytes to increase proteoglycan production. METHOD: We carried
      out an experiment, the effect of AdLMP-1 transfection on AF cells and
      chondrocytes in the production of sulfated-glycosaminoglycans, mRNA expression
      (aggrecan, type I, II collagen, LMP-1, BMP-2, and BMP-7), and immunofluorescence
      staining. AF cells and chondrocytes were grown in monolayer and treated for 6
      days with AdLMP1-green fluorescence protein (GFP) (10, 20, and 30 multiplicity of
      infection [MOI]). After 6 days, the sGAG content in the media was quantified
      using 1,9-dimethylmethylene blue staining. The mRNA expression was measured with
      real-time PCR after 20 MOI infection of AdLMP1-GFP. The each cells treated with
      20 MOI infection of AdGFP was used as a control group for the mRNA expression.
      The each cell group was immunofluorescence stained with each antibodies in the
      chamber slide at 3 x 10(4) cells/chamber. FINDINGS: 1) The sGAG production was
      maximum in 20 MOI AdLMP1-GFP infection on the AdLMP-1 treatment for both of AF
      cells and chondrocytes. 2) The mRNA expression of aggrecan, type I collagen, type
      II collagen, LMP-1, BMP-2, and BMP-7 is increased in both AF cells and
      chondrocytes in 20 MOI AdLMP1-GFP infection. 3) On the immunofluorescence
      staining results, the positive immunofluorescence stained cell numbers are
      increased after 20 MOI AdLMP1-GFP infection concordant with upregulation of mRNA
      expression. CONCLUSIONS: The AdLMP-1 treatments in AF cells and chondrocytes may
      be useful for cell transplantation therapy in disc degeneration.

PMID- 18618070
TI  - Large congenital transmesenteric hernia: a missed small-bowel atresia?
AB  - Internal hernias are uncommon diagnoses and represent rare causes of intestinal
      obstruction. Diagnoses are frequently made perioperatively. We present herein an
      illustrated case of transmesenteric hernia diagnosed in a pregnant woman who
      consulted for severe abdominal and dorsal pains. As CT scan was not possible
      because of the obstetric history, a decision to perform surgery was made because
      of acute pain, no history of previous surgery, and a plain erect X-ray disclosing
      early signs of intestinal obstruction. Perioperative findings were an ileal
      volvulus through a transmesenteric fossa circled by a unique ileocolic branch.
      This particular vascular disposition suggests transmesenteric hernias may be the
      first step in the constitution of congenital small-bowel atresia.

PMID- 18618072
TI  - Per-capita consumption of analgesics: a nine-country survey over 20 years.
AB  - There are no reliable data at present on use of analgesics in various countries.
      We compared per-capita consumption in nine different countries during the period
      1986-2005. The per-capita consumption was calculated on the basis of the sales
      figures of distributors to pharmacies and direct purchases by pharmaceutical
      companies in a sample of 1,000 pharmacies. The countries studied were: Australia,
      Austria, Belgium, Canada, France, Germany, Sweden, Switzerland, and the USA. In
      international comparison Austria, Switzerland, and Germany showed the lowest per
      capita consumption of analgesics (approx. 40-50 Standard Units (SU) per capita
      per year), while in Sweden and France consumption was three times as high. The
      correlation analysis over the various countries and time points confirmed a
      significant correlation between use of single analgesics and overall use of
      analgesics. In Germany, where an allegedly particularly high and constantly
      rising analgesic use has been discussed controversially (Meiner, Pharm Ind
      49:1247-1251, 1987), per-capita consumption of analgesics from 1980 to 2005
      remained practically unchanged at approx. 50 SU per capita per year. The
      prevalence of conditions inducing analgesic use shows appropriate analgesics use
      on an overall population level.

PMID- 18618071
TI  - Macrophage migration inhibitory factor may contribute to vasculopathy in systemic
      sclerosis.
AB  - Increasing evidence supports the concept of macrophage migration inhibitory
      factor (MIF) as a central proinflammatory cytokine in autoimmune diseases. To
      further evaluate its role in systemic sclerosis (SSc), serum levels of MIF were
      determined by enzyme-linked immunoassay, and correlations to clinical
      manifestations were analyzed in 43 patients. MIF levels were significantly
      increased in patients (median, 18.8; range, <0.015-189 ng/ml) in comparison to
      healthy controls (n=43, 8.0, <0.015-36.5 ng/ml; P<0.0005). MIF values were higher
      in diffuse than in limited cutaneous SSc (P<0.005). Patients with pulmonary
      hypertension and recurrent digital ulcers showed higher MIF levels than patients
      without these manifestations (P<0.005). This association was also observed in
      limited cutaneous SSc. Sequential studies revealed decreased MIF levels after
      initiation of immunosuppressive therapy. MIF levels were not significantly
      different in patients with and without macrovascular disease of the peripheral
      arteries. The results suggest that MIF might contribute to inflammation and
      vasculopathy in SSc.

PMID- 18618073
TI  - Iatrogenic rectal diverticulum in patients treated with transanal stapled
      techniques.
AB  - PURPOSE: The aim of this study was to demonstrate the possibility of rectal
      diverticula developing in patients treated with endoanal circular staplers for
      haemorrhoids (Longo's stapled haemorrhoidectomy) or obstructed defaecation
      syndrome [stapled transanal rectal resection (STARR)]. MATERIALS AND METHODS:
      Between January 2005 and December 2006, we carried out 634 defaecographic
      examinations. Of these, 45 were postoperative follow-up studies of patients who
      had been treated with the Longo technique (n = 13) or STARR technique (n = 32).
      RESULTS: Seven out of 45 patients, five of whom were women treated with the Longo
      technique and two men with the STARR technique, developed rectal diverticula. One
      diverticulum was located on the left lateral rectal wall, four on the posterior
      wall and two on the anterior wall. All diverticula had arisen from the surgical
      suture point. In one case, the diverticulum was discovered incidentally during a
      double-contrast barium enema. One of the male patients, who had been treated with
      the Longo procedure 5 years earlier, developed acute pain due to faecal stasis in
      a widenecked diverticulum abutting the posterior rectal wall. CONCLUSIONS: The
      use of endorectal stapling devices can lead to focal weakness at the point of
      surgical suture on the rectal wall and predispose to the development of rectal
      diverticula.

PMID- 18618074
TI  - Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR
      treatments, dependence on radiobiological parameters, and treatment optimisation.
AB  - PURPOSE: This study was undertaken to compare the biological efficacy of
      different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of
      gynaecological lesions, to identify the causes of possible nonuniformity and to
      optimise treatment through customised calculation. MATERIALS AND METHODS: The
      study considered 110 patients treated between 2001 and 2006 with external beam
      radiation therapy and/or brachytherapy with either LDR (afterloader Selectron,
      (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments
      were compared in terms of biologically effective dose (BED) to the tumour and to
      the rectum (linear-quadratic model) by using statistical tests for comparisons
      between independent samples. RESULTS: The difference between the two treatments
      was statistically significant in one case only. However, within each technique,
      we identified considerable nonuniformity in therapeutic efficacy due to
      differences in fractionation schemes and overall treatment time. To solve this
      problem, we created a Microsoft Excel spreadsheet allowing calculation of the
      optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding
      toxicity threshold (BED(rectum)). CONCLUSIONS: The efficacy of a treatment may
      vary as a result of several factors. Customised radiobiological evaluation is a
      useful adjunct to clinical evaluation in planning equivalent treatments that
      satisfy all dosimetric constraints.

PMID- 18618075
TI  - Treatment of Budd-Chiari syndrome with transjugular intrahepatic portosystemic
      shunt (TIPS).
AB  - PURPOSE: This study was performed to evaluate the safety and efficacy of
      transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of patients
      affected by Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: From January 1999
      to December 2006, 15 patients (seven male and eight female subjects, age range 7
      52 years) with BCS uncontrolled by medical therapy were treated with TIPS
      placement. In seven cases BCS was idiopathic, in four it was caused by
      myeloproliferative disorders and in four by other disorders. One patient also had
      portal vein thrombosis. In 5/15 cases TIPS was created through a transcaval
      approach. Eight patients (53.4%) received a bare stent, and seven (46.6%)
      received a stent graft. The follow-up lasted a median of 29.4 (range 3.2-68)
      months. RESULTS: Technical success was achieved in all patients without major
      complications. TIPS was very effective in decreasing the portosystemic pressure
      gradient from 26.2+/-5.8 to 10+/-6.2 mmHg. All patients but two were alive at the
      time of writing. Acute leukaemia was the cause of the single early death and was
      unrelated to the procedure. The patient with portal vein thrombosis underwent
      thrombolysis before TIPS, but the vein occluded again after 3 weeks, and the
      patient died 6 months later. The other patients showed significant improvements
      in liver function, ascites and symptoms related to portal hypertension. Primary
      patency was 53.3%, and primary assisted patency was 93.3%. No patient required or
      was scheduled for liver transplantation. CONCLUSIONS: TIPS is an effective and
      safe treatment for BCS and may be considered a valuable alternative to
      traditional surgical portosystemic shunting or liver transplantation.

PMID- 18618076
TI  - Dual-phase FDG-PET: delayed acquisition improves hepatic detectability of
      pathological uptake.
AB  - PURPOSE: The aim of this study was to evaluate whether the acquisition of delayed
      images could improve the detectability of liver pathological uptakes. MATERIALS
      AND METHODS: Ninety-five consecutive patients with suspected liver metastases
      underwent a dual-phase positron emission tomography (PET) scan. All patients
      underwent a whole-body PET/computed tomography (CT) scan (PET-1) acquired 1 h
      post [18F]fluorodeoxyglucose (FDG) injection, and a liver PET/CT scan [that is,
      one or two fields of view (FOV) of the upper abdomen; PET-2] acquired 2 h
      postinjection. In all cases, image reconstruction was performed as 3D
      reconstruction algorithm Fourier rebinning (FORE) iterative, FOV 50 cm, image
      matrix size 128 x 128. Both studies were evaluated qualitatively and
      semiquantitatively [background standard uptake values (SUV)mean of the liver,
      lesion SUVmax and SUVmean and ratio SUVmean lesion/background). RESULTS: Thirty
      seven of 95 patients (38.9%) presented liver lesions at both PET-1 and PET-2
      exams, whereas there were two (2.2%) only at PET-2. Eighty-one liver lesions were
      identified at both PET studies, whereas there were nine (11.1%) only at PET-2.
      Furthermore, at PET-2, we had a statistically significant reduction of SUVmean
      background values (p < 0.001, Wilcoxon test) and a concomitant increase of
      SUVmean lesion values (p < 0.001, Wilcoxon test), ratio lesion to background (p <
      0.001, Wilcoxon test). CONCLUSIONS: Acquisition of delayed images improved the
      hepatic detection of pathological FDG uptake.

PMID- 18618077
TI  - Evaluation of white matter damage in patients with Alzheimer's disease and in
      patients with mild cognitive impairment by using diffusion tensor imaging.
AB  - PURPOSE: The objective of this study was to evaluate white matter tissue damage
      in patients with Alzheimer's disease (AD) and in patients with mild cognitive
      impairment (MCI) using diffusion tensor imaging (DTI). MATERIALS AND METHODS:
      Forty-seven subjects were evaluated: 14 patients with AD, 15 with MCI and 18
      healthy volunteers. All subjects were studied using conventional magnetic
      resonance imaging (MRI) and DTI (32 directions) with a 1.5 T magnet. Fractional
      anisotropy (FA) was measured in the following regions: frontal, occipital,
      parietal and temporal white matter and in the genu and splenium of the corpus
      callosum. The results were compared between the different groups and correlated
      with the Mini-Mental State Evaluation (MMSE) scores. RESULTS: A statistically
      significant difference was obtained between controls and MCI patients (p < 0.007)
      and between controls and AD patients (p < 0.05) with regard to FA of the white
      matter in the splenium. A statistically significant difference was obtained
      between controls and AD patients with regard to FA in the genu (p < 0.016).
      Moreover, there was a statistically significant difference between controls and
      AD patients considering the genu (p < 0.016) and the frontal white matter on the
      right side (p < 0.024). The MMSE scores correlated with the FA values measured in
      the genu, the splenium and frontal white matter on the right side. No significant
      differences were identified between patients with AD and those with MCI.
      CONCLUSIONS: DTI could be of value in the early detection of white-matter damage
      in patients with MCI and AD. The DTI values correlate with the neuropsychological
      tests.

PMID- 18618078
TI  - Postpartum bilateral transient osteoporosis of the hip: MR imaging findings in
      three cases.
AB  - PURPOSE: Transient osteoporosis of the hip (TOH), associated with pregnancy, is a
      self-limiting skeletal disorder affecting women, usually in the third trimester,
      which resolves spontaneously within few months postpartum. Bilateral involvement
      is rare. Involvement postpartum has not been described. We report three patients
      with postpartum presentation of bilateral TOH. MATERIALS AND METHODS: Three
      pregnant women who presented with acute bilateral hip pain just after delivering
      their first child are reported. None of them had any past history of joint
      problems, recent injury, alcohol abuse or corticosteroid administration. Magnetic
      resonance (MR) imaging examinations were performed on 1.5-Tesla magnets using
      standard protocols. RESULTS: Bone marrow oedema, with normal joint space and
      intact articular surfaces, was depicted in all six hips. MR imaging findings with
      clinical correlation confirmed the diagnosis of TOH. CONCLUSIONS: TOH associated
      with pregnancy does not necessarily occur in the third trimester of pregnancy and
      may be bilateral.

PMID- 18618079
TI  - How much do GOLD stages reflect CT abnormalities in COPD patients?
AB  - PURPOSE: Severity of chronic obstructive pulmonary disease (COPD) can be graded
      using the classification released in the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) report. Such classification is essentially based
      on spirometry and does not recognise the role of other measures. The aim of this
      study was to assess whether the GOLD stages correlate with the extent of
      pulmonary emphysema and other ancillary computed tomography CT features in a
      population of smokers with stable COPD. MATERIALS AND METHODS: Based on clinical
      assessment and lung-function testing, patients were classified according to the
      GOLD criteria. CT scans were visually evaluated for extent of emphysema and
      airway abnormalities. RESULTS: A total of 43 patients were enrolled. The amount
      of emphysema was described as minimal in six patients with stage 0, and as
      moderate in seven patients with stage 0. In stages I and II, the extent of
      emphysema ranged from minimal to severe, whereas we observed the presence of
      severe emphysema in most patients in stages III and IV. According to the
      regression model, only CT emphysema extent independently predicted the GOLD stage
      (r2 = 0.58; p < 0.001). The cutoff value of emphysema extent of 31.5% allowed us
      to distinguish patients with a GOLD stage > or = III. CONCLUSIONS: Although we
      found a significant correlation between CT emphysema extent and GOLD stages,
      different percentage of emphysema extent can be observed among each GOLD stage.
      The upper limit of 31.5% of emphysema extent may indicate a boundary for a
      clinically worsening status.

PMID- 18618080
TI  - The incidence of associated fractures of the upper limb in fractures of the
      radial head.
AB  - Radial head fractures are common injuries. In American publications, one-third of
      the patients with these fractures have been shown to have associated injuries.
      The aim of this retrospective study is to describe the epidemiology of radial
      head fractures and associated fractures of the ipsilateral upper extremity in a
      European population. This study describes the epidemiology of radial head and
      associated fractures of the upper extremity in a Dutch population by a
      retrospective radiographic review of all patients with a radial head fracture
      between 1 January 2006 and 1 July 2007. A total of 147 radial head fractures were
      diagnosed in 145 patients. The incidence in the general population was 2.5 per
      10.000 per year. The average age was 45.9 (SD 17.3) years and male-female ratio
      was 2:3. The mean age of males was significantly lower (37.1, SD 14.2 years) than
      of women (53.9, SD 16.4 years). Associated fracture of the upper extremity was
      found in 10.2%. Coronoid fractures were most common (4.1%). Associated upper limb
      fractures in patients with a radial head fracture are common in the European
      population. It is of clinical importance to suspect associated lesions and to
      perform a thorough physical examination and additional radiological examination
      on demand.

PMID- 18618081
TI  - A phase II multicenter study of L-alanosine, a potent inhibitor of adenine
      biosynthesis, in patients with MTAP-deficient cancer.
AB  - OBJECTIVE: Methylthioadenosine phosphorylase (MTAP)-deficient tumors are
      dependent on the de novo purine synthesis pathway. These cancers are potential
      targets for selective chemotherapy with inhibitors of de novo adenine synthesis
      such as L-alanosine [L-2-amino-3-(N-hydroxy-N-nitrosamino) propionic acid]. This
      phase II study was designed to evaluate the efficacy and safety of L-alanosine in
      patients with MTAP-deficient solid tumors. METHODS: Patients with mesothelioma,
      non-small cell lung cancer (NSCLC), soft tissue sarcoma, osteosarcoma, or
      pancreatic cancer whose tumors were MTAP deficient by immunohistochemistry were
      eligible. Patients received L-alanosine at a starting dose of 80 mg/m(2) by
      continuous intravenous infusion daily for 5 days every 21 days. Computed
      tomography scans or magnetic resonance imaging were performed every 3 cycles.
      RESULTS: 65 patients (16 mesothelioma, 13 NSCLC, 15 soft tissue sarcoma, 7
      osteosarcoma, 14 pancreatic cancer) were enrolled at 19 centers; 55 were
      evaluable for response. There were no objective responses; 24% had s disease,
      including 2 patients with mesothelioma who had prolonged stable disease lasting
      7.5 and 15.2 months, respectively. Grade 3/4 toxicities included mucositis 11%,
      fatigue 6%, nausea 3%, and renal failure 1.5%. CONCLUSION: At this dose and
      schedule, L-alanosine was ineffective in patients with advanced MTAP-deficient
      tumors.

PMID- 18618083
TI  - Loss of visual function after repeated intravitreal injections of triamcinolone
      acetonide in refractory uveitic macular oedema.
AB  - PURPOSE: The effects of intravitreal triamcinolone acetonide on macular oedema
      have been evaluated in many studies. Good short-time effects are usually reported
      on visual function and macular oedema. However, adverse events like intraocular
      hypertension and cataract formation have been described in humans, and retinal
      toxicity is found in experimental studies. CASE REPORT: We report on a 56-year
      old male patient with a bilateral macular oedema in idiopathic intermediate
      uveitis, treated with two and six intravitreal injections of triamcinolone
      acetonide, respectively, and followed for 6 years. RESULTS: The macular oedema
      disappeared after each intravitreal injection, but each time it recidivated some
      months later. Visual acuity improved only after the first injections. After six
      intravitreal injections, visual acuity was limited to counting fingers in the
      absence of macular oedema. OCT and ERG results show central and peripheral
      retinal damage that could be a consequence of a retinotoxic property of
      triamcinolone acetonide. CONCLUSION: Repeated intravitreal injection of
      triamcinolone acetonide does not show any long-term efficacy on uveitic macular
      oedema and can even lead to irreversible global retinal damage.

PMID- 18618082
TI  - A phase I study of bortezomib, etoposide and carboplatin in patients with
      advanced solid tumors refractory to standard therapy.
AB  - PURPOSE: To evaluate the toxicity, pharmacological, and biological properties of
      the combination of bortezomib, etoposide, and carboplatin in adults with advanced
      solid malignancies. PATIENTS AND METHODS: Patients received escalating doses of
      bortezomib, etoposide, and carboplatin every 21 days. Surrogate markers of
      angiogenesis were evaluated. RESULTS: Twenty-four patients received 64 courses of
      therapy. The most common treatment-related adverse events were myelosuppression.
      Dose-limiting grade 3 and 4 neutropenia and thrombocytopenia were observed when
      bortezomib was given on days 1, 4, 8, 11. With revised dosing, the maximum
      tolerated dose (MTD) of bortezomib 0.75 mg/m(2) (days 1, 8), etoposide 75 mg/m(2)
      (days 1-3), and carboplatin AUC 5 (day 1) was well tolerated, and are the
      recommended doses for further studies with this combination. No objective
      responses were observed, however stable disease was noted for greater or equal to
      four cycles in nine highly refractory patients.

PMID- 18618084
TI  - Gene trapping: an antibody-dependent approach for verifying integration in your
      favorite gene.
AB  - Gene trapping is used to introduce genome-wide insertional mutations in embryonic
      stem cells. Determining the integration site is based on highthroughput PCR,
      which has inevitable possibilities for mistakes, thus necessitating clone
      verification prior to the generation of mutant mice. Here, we propose a rapid
      method to validate gene identity based on the fact that many high throughput gene
      trapping integrations result in fusion proteins encompassing the N-terminal
      portion of the gene of interest and LacZ being expressed in embryonic stem cells.
      Our method utilizes an immunoprecipitation assay using a specific N-terminal
      directed antibody to the protein product of the gene of interest followed by a
      color LacZ assay of the immunoprecipitate, strongly supporting the formation of a
      fusion protein when the color develops.

PMID- 18618085
TI  - Synthesis of cephalexin in aqueous medium with carrier-bound and carrier-free
      penicillin acylase biocatalysts.
AB  - The use of very high substrate concentrations favors the kinetically controlled
      synthesis of cephalexin with penicillin acylase (PA) not only by Michaelian
      considerations, but also because water activity is depressed, so reducing the
      rates of the competing reactions of product and acyl donor hydrolysis. Commercial
      PGA-450, glyoxyl agarose immobilized (PAIGA) and carrier-free cross-linked enzyme
      aggregates of penicillin acylase (PACLEA) were tested in aqueous media at
      concentrations close to the solubility of nucleophile and at previously
      determined enzyme to nucleophile and acid donor to nucleophile ratios. The best
      temperature and pH were determined for each biocatalyst based on an objective
      function considering conversion yield, productivity, and enzyme stability as
      evaluation parameters. Stability was higher with PAIGA and specific productivity
      higher with PACLEA, but best results based on such objective function were
      obtained with PGA-450. Yields were stoichiometric and productivities higher than
      those previously reported in organic medium, which implies significant savings in
      terms of costs and environmental protection. At the optimum conditions for the
      selected biocatalyst, operational stability was determined in sequential batch
      reactor operation. The experimental information gathered is being used for a
      technical and economic evaluation of an industrial process for enzymatic
      production of cephalexin in aqueous medium.

PMID- 18618086
TI  - Novel N-terminal cleavage of APP precludes Abeta generation in ACAT-defective
      AC29 cells.
AB  - A common pathogenic event that occurs in all forms of Alzheimer's disease is the
      progressive accumulation of amyloid beta-peptide (Abeta) in brain regions
      responsible for higher cognitive functions. Inhibition of acyl-coenzyme A:
      cholesterol acyltransferase (ACAT), which generates intracellular cholesteryl
      esters from free cholesterol and fatty acids, reduces the biogenesis of the Abeta
      from the amyloid precursor protein (APP). Here we have used AC29 cells, defective
      in ACAT activity, to show that ACAT activity steers APP either toward or away
      from a novel proteolytic pathway that replaces both alpha and the amyloidogenic
      beta cleavages of APP. This alternative pathway involves a novel cleavage of APP
      holoprotein at Glu281, which correlates with reduced ACAT activity and Abeta
      generation in AC29 cells. This sterol-dependent cleavage of APP occurs in the
      endosomal compartment after internalization of cell surface APP. The resulting
      novel C-terminal fragment APP-C470 is destined to proteasomal degradation
      limiting the availability of APP for the Abeta generating system. The proportion
      of APP molecules that are directed to the novel cleavage pathway is regulated by
      the ratio of free cholesterol and cholesteryl esters in cells. These results
      suggest that subcellular cholesterol distribution may be an important regulator
      of the cellular fate of APP holoprotein and that there may exist several
      competing proteolytic systems responsible for APP processing within the endosomal
      compartment.

PMID- 18618087
TI  - Lack of ACTH and androgen receptor expression in a giant adrenal myelolipoma
      associated with 21-hydroxylase deficiency.
AB  - Myelolipomas of the adrenal gland are benign, nonfunctioning tumors. Patients
      with congenital adrenal hyperplasia sometimes develop large and bilateral
      myelolipomas. Although the precise pathogenesis of myelolipomas remains unclear,
      prolonged stimulation with high levels of adrenocorticotropic hormone (ACTH) or
      adrenal androgens are assumed to have a causative role. To clarify the role of
      ACTH and androgen in the pathogenesis of myelolipoma, we report a case of giant
      adrenal myelolipoma in a patient with poorly controlled congenital adrenal
      hyperplasia. A 43-year-old female was diagnosed with congenital adrenal
      hyperplasia at 6 years of age because of ambiguous genitalia. She had high plasma
      ACTH and 17-hydroxyprogesterone levels. Abdominal computed tomography showed a
      huge mass on the left adrenal gland, and an enlarged right adrenal mass. Genetic
      testing for CYP21A2 was performed and revealed that her genotype was IVS2
      13A/C>G/I172N. Adrenalectomy for the left-side tumor was performed. Histological
      study revealed that the tumor consisted of fat cells and myeloid components,
      findings compatible with adrenal myelolipoma. Neither ACTH receptors nor androgen
      receptor was over-expressed in the tumor. Our finding that the tumor did not over
      express ACTH or androgen receptor suggests a limited direct role for these
      hormones in the development of the myelolipoma.

PMID- 18618088
TI  - [Flexible 'chip-on-the-tip' endoscopy for larynx diagnostics].
AB  - BACKGROUND: Laryngoscopic procedures can be performed either with rigid or with
      flexible endoscopes (FE). While the benefit of FEs is a better reflection of the
      physiological situation, rigid endoscopes (RE) usually offer better image
      quality. Modern flexible 'chip-on-the-tip' endoscopes promise to combine the
      advantages of both procedures. MATERIAL AND METHODS: A total of 38 patients with
      dysphonia were examined with RE, conventional FE, and"chip-on-the-tip" endoscopes
      (TCE). Image quality was assessed and compared and procedures were evaluated with
      regard to patient contentment. RESULTS: In all cases image quality of TCE and RE
      was better than conventional FE. In 55% of cases image quality of TCE and RE was
      comparable, in 24% RE was judged to be better and in 21% TCE was better. Patient
      contentment was higher for FE in comparison with RE. CONCLUSION: 'Chip-on-the
      tip' endoscopes combine the advantages of both RE and FE with respect to a
      physiological examination and high image quality.

PMID- 18618089
TI  - [Biochemical bone resorption markers during the healing of osteoporotic
      fractures].
AB  - BACKGROUND: This study investigated the progression and clinical relevance of
      biochemical resorption marker values during fracture healing in osteoporosis.
      PATIENTS AND METHODS: In 44 patients with distal radius fractures and 29 patients
      without fractures, the blood and urine concentrations of pyridinoline (PYD),
      deoxypyridinoline (DPD), N-telopeptides (NTx), and bone sialoprotein (BSP) were
      recorded on the day of trauma as well as during further progression. All
      postmenopausal patients underwent bone density measurement. Accordingly, patients
      were divided into premenopausal, postmenopausal osteoporotic, and postmenopausal
      nonosteoporotic groups. RESULTS: Between the groups, PYD, DPD, and NTx showed
      significant differences in their initial values. However, their further relative
      progression was primarily affected by the chosen therapy. CONCLUSION: Bone
      resorption markers can diagnostically point to osteoporosis and are significant
      parameters in fracture healing.

PMID- 18618090
TI  - [Refixation of the M. recti abdomini on the symphysis in traumatic pubis
      symphysis disruption. Reconstruction to the original anatomic situation].
AB  - Pelvic fractures may accompany other injuries and can be life-threatening. In
      addition, the rectus abdominis muscles might also be torn. During fracture
      reduction, these muscles are fixed to their insertions. The goal should be
      reconstruction as close as possible to the original anatomic situation.
      Refixation of the vertical rectus muscles that have retreated cranially results
      in preventing development of lower abdominal wall hernia.A hernia in combination
      with a symphysis disruption has been reported very seldom in the available
      literature. We report here on a case of hernia that developed postoperatively
      after treatment of traumatic pubic symphysis rupture. Primary open reduction of
      the symphysis was carried out and the rectus abdominis muscles were refixed to
      the bones. An attempt was made to repair the incisional hernia that developed by
      tightening the fascia. Two and a half years after the accident, the patient
      developed a diastasis and an abdominal wall hernia, which were repaired by
      refixation of the rectus abdominis muscles to the bones with Mersilene bands.
      Results nine months after the reconstructive surgical intervention show a firm
      abdominal wall without recurrence.This case shows that even 2.5 years after an
      accident, the rectus abdomini muscles can be fixed with Mersilene bands to the
      bone and anatomic reconstruction of the abdominal wall can be carried out.

PMID- 18618091
TI  - Within-population variation in ejaculate characteristics in a prolonged breeder,
      Peron's tree frog, Litoria peronii.
AB  - Sperm number is often a good predictor of success in sperm competition; however,
      it has become increasingly clear that, for some species, variation in probability
      of paternity cannot be explained by sperm number alone. Intraspecific variation
      in ejaculate characteristics, such as the number of viable sperm and sperm
      longevity, may play an equally important role in determining fertilization
      success. Here, we assess variation among ejaculates in three factors that may
      contribute to fertilization success (number of sperm per ejaculate, viability,
      and longevity), in a population of Peron's tree frog (Litoria peronii). We
      detected large variation among males in the number of sperm per ejaculate and the
      proportion of viable sperm within ejaculates, which could not be explained by
      variation in either male size or body condition. However, the proportion of
      viable sperm released by males increased over the season. Finally, we assessed
      sperm longevity (proportion viable sperm determined using a dual-fluorochrome
      vital dye) at two different temperatures. At 23 degrees C, on average, 75% of
      sperm remained viable after 2 h, but there were significant differences amongst
      males with the percentage of viable sperm ranging from 43% to 95%. For sperm
      incubated at 4 degrees C, ejaculates varied fivefold in sperm longevity with some
      males having 50% viable sperm after 5 days. Our data suggest that ejaculate
      characteristics (sperm number, viability, and longevity) vary widely in Peron's
      tree frog and may therefore play an important role in determining siring success
      both in the presence and absence of sperm competition. We discuss the results in
      relation to selection on ejaculate traits via natural and sexual selection in
      this and other amphibians.

PMID- 18618092
TI  - Significance of organic matter in Eocene turbidite sediments (SE Pyrenees,
      Spain).
AB  - Although turbidite deposits are classically considered to be good reservoir rocks
      for oil and gas, there are no reports concerning their source rock potential in
      the literature. The sediments from the Vallfogona Formation in the South-Eastern
      Pyrenees present numerous organic matter-rich levels interbedded in sandstones
      and coarse turbidite deposits. Two types of organic matter deposits were
      differentiated on the basis of organic geochemistry and petrography: type A and
      type B. Type A was deposited in a carbonate marine environment under hypersaline
      conditions as indicated mainly by even/odd n-alkane predominance, pristane and
      phytane ratio (Pr/Ph) < 1, presence of gammacerane, and trisnorneohopane over
      trisnorhopane ratio (Ts/Tm) > 1. Type B was deposited in a more mud-rich marine
      environment evidenced by the predominance of odd n-alkane, Pr/Ph > or = 1, Ts/Tm
      < 1, the absence of gammacerane, similar concentrations of the C(27) and C(29)
      regular steranes, and the greater abundance of C(27) diasteranes. Turbidite
      facies can be regarded as an environment where organic matter sedimentation is
      heterogeneous in type and amount. This study suggests that turbidite deposits
      with interbedded organic matter-rich levels may act as a combined source
      reservoir system.

PMID- 18618093
TI  - [Tremor. Differential diagnosis and treatment].
AB  - Tremor is one of the most frequent neurological signs; the diagnosis is mainly
      clinical. The most frequent tremor is essential tremor, which manifests itself as
      a postural and kinetic tremor. Tremor may occur not only in the hands, but also
      in the head and voice. Parkinsonian tremor is a tremor at rest; the legs and face
      are frequently involved. Orthostatic tremor mainly manifests itself in the legs
      and gives rise to postural instability. Dystonic tremor is an action tremor of
      the affected region of the body. Drug therapy mostly depends on the clinical
      manifestation. Postural and action tremors respond to beta blockers, primidone,
      some antiepileptics and benzodiazepines. Classical rest tremors are improved by
      dopaminergic substances or anticholinergics. Dystonic tremor may be successfully
      treated by injecting botulinum toxin. Orthostatic tremor responds to gabapentin
      or benzodiazepines in some patients. In patients with severely disability,
      implantation of thalamic stimulation electrodes may be considered.

PMID- 18618094
TI  - Quantitative trait loci associated with adaptation to Mediterranean dryland
      conditions in barley.
AB  - The objective of the present study was to identify quantitative trait loci (QTL)
      influencing agronomic performance across rain fed Mediterranean environments in a
      recombinant inbred line (RIL) population derived from the barley cultivars ER/Apm
      and Tadmor. The population was tested in four locations (two in Syria and two in
      Lebanon) during four consecutive years. This allowed the analysis of marker main
      effects as well as of marker by location and marker by year within location
      interactions. The analysis demonstrated the significance of crossover
      interactions in environments with large differences between locations and between
      years within locations. Alleles from the parent with the higher yield potential,
      ER/Apm, were associated with improved performance at all markers exhibiting main
      effects for grain yield. The coincidence of main effect QTL for plant height and
      yield indicated that average yield was mainly determined by plant height, where
      Tadmor's taller plants, being susceptible to lodging, yielded less. However, a
      number of crossover interactions were detected, in particular for yield, where
      the Tadmor allele improved yield in the locations with more severe drought
      stress. The marker with the highest number of cross-over interactions for yield
      and yield component traits mapped close to the flowering gene Ppd-H2 and a
      candidate gene for drought tolerance HVA1 on chromosome 1H. Effects of these
      candidate genes and QTL may be involved in adaptation to severe drought as
      frequently occurring in the driest regions in the Mediterranean countries.
      Identification of QTL and genes affecting field performance of barley under
      drought stress is a first step towards the understanding of the genetics behind
      drought tolerance.

PMID- 18618095
TI  - Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during
      hyperglycaemic clamps.
AB  - AIMS/HYPOTHESIS: Genome-wide association studies have recently identified novel
      type 2 diabetes susceptibility gene regions. We assessed the effects of six of
      these regions on insulin secretion as determined by a hyperglycaemic clamp.
      METHODS: Variants of the HHEX/IDE, CDKAL1, SLC30A8, IGF2BP2 and CDKN2A/CDKN2B
      genes were genotyped in a cohort of 146 participants with NGT and 126 with IGT
      from the Netherlands and Germany, who all underwent a hyperglycaemic clamp at 10
      mmol/l glucose. RESULTS: Variants of CDKAL1 and IGF2BP2 were associated with
      reductions in first-phase insulin secretion (34% and 28%, respectively). The
      disposition index was also significantly reduced. For gene regions near HHEX/IDE,
      SLC30A8 and CDKN2A/CDKN2B we did not find significant associations with first
      phase insulin secretion (7-18% difference between genotypes; all p > 0.3). None
      of the variants showed a significant effect on second-phase insulin secretion in
      our cohorts (2-8% difference between genotypes, all p > 0.3). Furthermore, the
      gene variants were not associated with the insulin sensitivity index.
      CONCLUSIONS: Variants of CDKAL1 and IGF2BP2 attenuate the first phase of glucose
      stimulated insulin secretion but show no effect on the second phase of insulin
      secretion. Our results, based on hyperglycaemic clamps, provide further insight
      into the pathogenic mechanism behind the association of these gene variants with
      type 2 diabetes.

PMID- 18618096
TI  - Safety and efficacy of ultrasound assistance during internal jugular vein
      cannulation in neurosurgical infants.
AB  - OBJECTIVE: Ultrasound guidance (USG) for internal jugular cannulation is the best
      solution in difficult settings where paediatric patients are involved. This is an
      outcome study on efficacy and complications of the USG for the internal jugular
      vein (IJV) cannulation in neurosurgical infants as well as an ultrasound study of
      anatomical findings of the IJVs in infants. DESIGN AND SETTINGS: A prospective
      study conducted in two Academic Neurosurgical hospitals. PARTICIPANTS: In 191
      babies (body weight <15 kg), anatomical findings were studied. We performed CVC
      echo guided placement in 135/191 infants (weighting <10 kg). RESULTS: After a
      brief training period, both institutions adopted a common protocol and USG
      device. We obtained successful cannulation in all patients. Carotid puncture
      (1.5%) was the only main complication registered and minor complications were
      poor. Time required for cannulation was 12.5 +/- 5.7 min. Anatomical findings (in
      191 patients) were IJV laterality in 34.6% cases, IJV antero-lateral in 59.7% and
      anterior in 5.7%. A linear relation was found between weight and internal jugular
      vein diameter even if R(2) = 0.43 and the model cannot be used to predict the
      exact size of the vein. In 62/135 babies weighting <10 kg, anatomical
      measurements were done in supine and Trendelemburg position. Trendelemburg
      position increases significantly (P < 0.001) IJV diameter, but not IJV depth.
      CONCLUSIONS: We considered ultrasound guidance as the first choice in infants
      because it can enhance IJV cannulation success, safety, and allows one to measure
      relationships and diameter of the IJV and optimise the central line positioning.

PMID- 18618097
TI  - Inhibition and induction of human cytochrome P450 enzymes: current status.
AB  - Variability of drug metabolism, especially that of the most important phase I
      enzymes or cytochrome P450 (CYP) enzymes, is an important complicating factor in
      many areas of pharmacology and toxicology, in drug development, preclinical
      toxicity studies, clinical trials, drug therapy, environmental exposures and risk
      assessment. These frequently enormous consequences in mind, predictive and pre
      emptying measures have been a top priority in both pharmacology and toxicology.
      This means the development of predictive in vitro approaches. The sound
      prediction is always based on the firm background of basic research on the
      phenomena of inhibition and induction and their underlying mechanisms;
      consequently the description of these aspects is the purpose of this review. We
      cover both inhibition and induction of CYP enzymes, always keeping in mind the
      basic mechanisms on which to build predictive and preventive in vitro approaches.
      Just because validation is an essential part of any in vitro-in vivo
      extrapolation scenario, we cover also necessary in vivo research and findings in
      order to provide a proper view to justify in vitro approaches and observations.

PMID- 18618098
TI  - Mechanism of the prostanoid TP receptor agonist U46619 for inducing emesis in the
      ferret.
AB  - U46619 is a potent thromboxane A(2) mimetic with emesis-inducing actions that are
      mediated via prostanoid TP receptors. We investigated its emetic mechanism of
      action in more detail using the ferret as model animal. The emesis induced by
      U46619 (30 microg/kg, intraperitoneal) was antagonized significantly by (+)
      (2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine hydrochloride (CP-99,994; 1
      and 10 mg/kg; P < 0.05) and metoclopramide (0.3 and 3 mg/kg), but not by
      domperidone (3 mg/kg), sulpiride (0.1 mg/kg), ondansetron (0.1 and 1 mg/kg) alone
      or combined with droperidol (3 mg/kg), GR125487 (1 mg/kg), promethazine (3
      mg/kg), or scopolamine (3 mg/kg); GR 125487 (1 mg/kg) prevented the anti-emetic
      action of metoclopramide (3 mg/kg). U46619 0.3 microg administered into the
      fourth ventricle rapidly induced emesis. However, bilateral abdominal vagotomy
      was ineffective in reducing the emetic response (P > 0.05). Our data suggests
      that U46619 induces emesis via an extra-abdominal mechanism, probably within the
      brain. Metoclopramide probably has a mechanism of action to prevent U46619
      induced emesis via 5-HT(4) receptor activation and NK(1) tachykinin receptor
      antagonists could be useful to prevent emesis induced by TP receptor activation
      in man.

PMID- 18618099
TI  - Chronic nicotine improves cognitive performance in a test of attention but does
      not attenuate cognitive disruption induced by repeated phencyclidine
      administration.
AB  - RATIONALE: Nicotine-induced cognitive enhancement may be a factor maintaining
      tobacco smoking, particularly in psychiatric populations suffering from cognitive
      deficits. Schizophrenia patients exhibit higher smoking rates compared with the
      general population, suggesting that attempts to self-medicate cognitive
      schizophrenia deficits may underlie these high smoking levels. OBJECTIVES: The
      present study explored pro-cognitive effects of nicotine in a model of
      schizophrenia-like cognitive dysfunction to test this self-medication hypothesis.
      MATERIALS AND METHODS: We investigated whether chronic nicotine (3.16 mg/kg/day,
      base) would attenuate the performance disruption in the five-choice serial
      reaction time task (5-CSRTT, a task assessing various cognitive modalities,
      including attention) induced by repeated administration of phencyclidine (PCP),
      an N-methyl-D-aspartate receptor antagonist that induces cognitive deficits
      relevant to schizophrenia. RESULTS: Chronic nicotine administration shortened 5
      CSRTT response latencies under baseline conditions. Nicotine-treated rats also
      made more correct responses and fewer omissions than vehicle-treated rats.
      Replicating previous studies, repeated PCP administration (2 mg/kg, 30 min before
      behavioral testing for two consecutive days followed 2 weeks later by five
      consecutive days of PCP administration) decreased accuracy and increased response
      latencies, premature responding, and timeout responding. Chronic nicotine did not
      attenuate these PCP-induced disruptions. CONCLUSIONS: Chronic nicotine had pro
      cognitive effects by itself, supporting the hypothesis that cognitive enhancement
      may contribute to tobacco smoking. At the doses of nicotine and PCP used,
      however, no support was found for the hypothesis that the beneficial effects of
      nicotine on cognitive deficits induced by repeated PCP administration, assessed
      in the 5-CSRTT, are larger than nicotine effects in the absence of PCP.

PMID- 18618101
TI  - Determination of CYP activity in precision-cut liver slices: whether to use
      intact slices or slice homogenate.
AB  - Despite CYP induction in vitro in precision-cut liver slices (LS) is well
      documented, there are no standardised assays for determining CYP activity as a
      major end-point. In this paper, short-term assays with intact and homogenised LS
      from male and female rats were directly compared. We obtained similar results for
      7-ethoxycoumarine O-deethylation (ECOD) with LS from both sexes: higher basal
      activities were measured in LS homogenate, whereas slightly stronger induction by
      BNF was found with intact LS. CYP3A-dependent basal and dexamethasone (Dex)
      induced 2beta-, 15beta- and 6beta-testosterone hydroxylation (TH) rates were
      higher in both intact and homogenised LS from male compared to female rats. CYP3A
      induction in vitro could likewise be detected in intact and homogenised LS
      preferentially by determining 2beta- and 15beta-TH, with higher induction factors
      observed in LS from females. 6beta-TH seems to be less inducible in intact LS of
      males. In vivo pretreatment of liver donors with BNF and Dex did not
      substantially disturb the subsequent in vitro induction of ECOD and TH,
      respectively.

PMID- 18618102
TI  - Behavioural and electrophysiological analysis of strabismus in cats: modern
      context.
AB  - We studied the effects of paralytic strabismus on visual behaviour and
      binocularity of cortical visual mechanisms by immobilization of one eye in adult
      cats. Visual discrimination abilities of the immobilized eye were significantly
      diminished despite extensive training with one or both eyes. The deficits are not
      caused by the immobilization itself but appear to reflect an adaptive mechanism
      to deal with double vision. The deficits with the immobilized eye persisted even
      after section of the optic chiasm, which effectively removes the direct cortical
      competition of the two eyes. Single-cell electrophysiological recordings showed
      that cortical cellular responses are modified by the immobilization, with loss of
      binocularity in some cells and shifting of receptive fields of other cells that
      continued to respond to both eyes.

PMID- 18618100
TI  - A neurocognitive animal model dissociating between acute illness and remission
      periods of schizophrenia.
AB  - RATIONALE: The development and validation of animal models of the cognitive
      impairments of schizophrenia have remained challenging subjects. OBJECTIVE: We
      review evidence from a series of experiments concerning an animal model that
      dissociates between the disruption of attentional capacities during acute illness
      periods and the cognitive load-dependent impairments that characterize periods of
      remission. The model focuses on the long-term attentional consequences of an
      escalating-dosing pretreatment regimen with amphetamine (AMPH). RESULTS: Acute
      illness periods are modeled by the administration of AMPH challenges. Such
      challenges result in extensive impairments in attentional performance and the
      "freezing" of performance-associated cortical acetylcholine (ACh) release at
      pretask levels. During periods of remission (in the absence of AMPH challenges),
      AMPH-pretreated animals' attentional performance is associated with abnormally
      high levels of performance-associated cortical ACh release, indicative of the
      elevated attentional effort required to maintain performance. Furthermore, and
      corresponding with clinical evidence, attentional performance during remission
      periods is exquisitely vulnerable to distractors, reflecting impaired top-down
      control and abnormalities in fronto-mesolimbic-basal forebrain circuitry.
      Finally, this animal model detects the moderately beneficial cognitive effects of
      low-dose treatment with haloperidol and clozapine that were observed in clinical
      studies. CONCLUSIONS: The usefulness and limitations of this model for research
      on the neuronal mechanisms underlying the cognitive impairments in schizophrenia
      and for drug-finding efforts are discussed.

PMID- 18618103
TI  - Antiepileptic drug utilization in children from 1997-2005--a study from the
      Netherlands.
AB  - OBJECTIVE: To investigate the utilization of antiepileptic drugs (AEDs) in Dutch
      children and compare this with guidelines on the treatment of epilepsy in
      children. METHOD: From the Dutch Interaction Database (IADB.nl) we selected
      children aged 0-19 years who received at least one prescription for an AED (ATC
      code beginning with N03A) between 1997 and 2005. We calculated cumulative
      incidences and prevalences per 1000 children per year, stratified by age
      category, sex and type of AED, and the total number of months each patient
      received at least one prescription of AEDs, and we counted the number of person
      months and AEDs prescribed. For each AED, proportions of person-months were
      calculated for mono- and combination therapy. Kaplan-Meier survival analysis was
      used to analyse the duration of AED use, stratified by sex. RESULTS: The overall
      prevalence of the prescription of AEDs to children was constant at approximately
      4.0 per 1000 children during the years of the study. The overall cumulative
      incidence from 1997-2005 was 0.67 per 1000 children. When stratified by age
      category or sex, there were no relevant differences in incidence or prevalence.
      Valproic acid was the most frequently prescribed drug, followed by carbamazepine
      and lamotrigine. In 20.3% of all person-months, patients received combination
      therapy; of these, 34.2% received combination therapy for 3 person-months or
      less. The older AEDs were prescribed more often as monotherapy than combination
      therapy, in contrast with the newer AEDs, for which the opposite was true. The
      50% survival probability (= time period when 50% of children had stopped using
      AEDs) was around 2 years, with a significantly lower discontinuation of treatment
      for girls than boys (P = 0.04). CONCLUSION: The overall cumulative incidence of
      AEDs was determined to be 0.67 per 1000 children, and the prevalence 4.0 per 1000
      children. The most frequently prescribed drug is valproic acid, followed by
      carbamazepine and lamotrigine. The prescribing of AEDs seems to be in conformity
      with the overall recommendations of the guidelines on the treatment of epilepsy
      in children.

PMID- 18618104
TI  - 'Double trouble': incidental diagnosis of colonic duplication on spinal MRI.

PMID- 18618105
TI  - A snapshot of the Mamu-B genes and their allelic repertoire in rhesus macaques of
      Chinese origin.
AB  - The major histocompatibility complex class I gene repertoire was investigated in
      a large panel of rhesus macaques of Chinese origin. As observed in Indian
      animals, subjects of Chinese derivation display Mamu-B gene copy number
      variation, and the sum of expressed genes varies among haplotypes. In addition,
      these genes display differential transcription levels. The majority of the Mamu-B
      alleles discovered during this investigation appear to be unique for the
      population studied. Only one particular Mamu-B haplotype is shared between Indian
      and Chinese animals, and it must have been present in the progenitor stock.
      Hence, the data highlight the fact that most allelic polymorphism, and most of
      the Mamu-B haplotypes themselves, are of relatively recent origin and were most
      likely generated after the separation of the Indian and Chinese rhesus macaque
      populations.

PMID- 18618106
TI  - Comprehensive evaluation of occupational radiation exposure to intraoperative and
      perioperative personnel from 18F-FDG radioguided surgical procedures.
AB  - PURPOSE: The purpose of the current study was to comprehensively evaluate
      occupational radiation exposure to all intraoperative and perioperative personnel
      involved in radioguided surgical procedures utilizing (18)F-fluorodeoxyglucose
      ((18)F-FDG). METHODS: Radiation exposure to surgeon, anesthetist, scrub
      technologist, circulating nurse, preoperative nurse, and postoperative nurse,
      using aluminum oxide dosimeters read by optically stimulated luminescence
      technology, was evaluated during ten actual radioguided surgical procedures
      involving administration of (18)F-FDG. RESULTS: Mean patient dosage of (18)F-FDG
      was 699 +/- 181 MBq (range 451-984). Mean time from (18)F-FDG injection to
      initial exposure of personnel to the patient was shortest for the preoperative
      nurse (75 +/- 63 min, range 0-182) followed by the circulating nurse,
      anesthetist, scrub technologist, surgeon, and postoperative nurse. Mean total
      time of exposure of the personnel to the patient was longest for the anesthetist
      (250 +/- 128 min, range 69-492) followed by the circulating nurse, scrub
      technologist, surgeon, postoperative nurse, and preoperative nurse. Largest deep
      dose equivalent per case was received by the surgeon (164 +/- 135 microSv, range
      10-580) followed by the anesthetist, scrub technologist, postoperative nurse,
      circulating nurse, and preoperative nurse. Largest deep dose equivalent per hour
      of exposure was received by the preoperative nurse (83 +/- 134 microSv/h, range 0
      400) followed by the surgeon, anesthetist, postoperative nurse, scrub
      technologist, and circulating nurse. CONCLUSION: On a per case basis,
      occupational radiation exposure to intraoperative and perioperative personnel
      involved in (18)F-FDG radioguided surgical procedures is relatively small.
      Development of guidelines for monitoring occupational radiation exposure in (18)F
      FDG cases will provide reassurance and afford a safe work environment for such
      personnel.

PMID- 18618107
TI  - 99mTc-apcitide scintigraphy in patients with clinically suspected deep venous
      thrombosis and pulmonary embolism.
AB  - AIM: Detection of acute deep venous thrombosis (DVT) in patients presenting with
      clinical symptoms suggesting DVT and pulmonary embolism (PE) with (99m)Tc
      apcitide, a synthetic polypeptide, binding to glycoprotein IIb/IIIa receptors
      expressed on activated platelets is the objective of the study. MATERIALS AND
      METHODS: Nineteen patients (11 males, eight females) received within 24h after
      admission to the hospital a mean of 841 MBq (range 667 to 1,080) (99m)Tc-apcitide
      i.v. followed by planar recordings 10, 60, and 120 min after injection. Images
      were compared to the results of compression ultrasonography and/or phlebography.
      Patients with clinically suspected PE underwent spiral computed tomography or
      lung perfusion scans. RESULTS: (99m)Tc-apcitide scintigraphy showed acute clot
      formation in 14 out of 16 patients where the other imaging modalities suggested
      DVT. Positive scintigraphic results were seen up to 17 days after the onset of
      clinical symptoms. In three out of three patients without any proof of DVT,
      (99m)Tc-apcitide scintigraphy was truly negative. Glycoprotein receptor imaging
      showed only one segmental PE in six patients with imaging-proven subsegmental (N
      = 3) or segmental PE (N = 3). CONCLUSION: (99m)Tc-apcitide scintigraphy may be an
      easy and promising tool for the detection of acute clot formation in patients
      with DVT up to 17 days after the onset of clinical symptoms with a sensitivity of
      87% and a specificity of 100%. However, it failed to demonstrate PE in 83% of
      examined patients with proven PE.

PMID- 18618108
TI  - Radioembolisation with 90Y-microspheres: dosimetric and radiobiological
      investigation for multi-cycle treatment.
AB  - INTRODUCTION: Radioembolisation with (90)Y-microspheres is a new locoregional
      treatment of hepatic lesions, usually applied as single cycle. Multi-cycle
      treatments might be considered as a strategy to improve the risk-benefit balance.
      With the aim to derive suitable information for patient tailored therapy,
      available patients' dosimetric data were reviewed according to the linear
      quadratic model and converted into biological effective dose (BED) values. Single
      vs. multi-cycle approaches were compared through radiobiological perspective.
      MATERIALS AND METHODS: Twenty patients with metastatic lesions underwent
      radioembolisation. The (90)Y-administered activity (AA) was established in order
      to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL).
      BED was calculated setting alpha/beta = 2.5 Gy (NTL), 10 Gy (tumours); T
      (1/2,eff) = T (1/2,phys) = 64.2 h; T (1/2,rep) = 2.5 h (NTL), 1.5 h (tumours).
      The BED to NTL was considered as a constraint for multi-cycle approach. The AA
      for two cycles and the percent variations of AA, tumour dose, BED were estimated.
      RESULTS: In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy),
      AA was 1.7 (0.9-3.2) GBq, tumour dose was 130 (65-235) Gy, and tumour BED was 170
      (75-360) Gy. Considering two cycles, approximately 15% increase was found for AA
      and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10-35)
      Gy; tumour BED increase was 10 (3-11) Gy. In different protocols allowing 80 Gy
      to NTL, the BED sparing estimated was approximately 50 Gy (two cycles) and 65 Gy
      (three cycles). CONCLUSIONS: From a radiobiological perspective, multi-cycle
      treatments would allow administering higher activities with increased tumour
      irradiation and preserved radiation effects on NTL. Trials comparing single vs.
      multiple cycles are suggested.

PMID- 18618109
TI  - TIMP-1-GPI in combination with hyperthermic treatment of melanoma increases
      sensitivity to FAS-mediated apoptosis.
AB  - Resistance to apoptosis is a prominent feature of malignant melanoma.
      Hyperthermic therapy can be an effective adjuvant treatment for some tumors
      including melanoma. We developed a fusion protein based on the tissue inhibitor
      of matrix metalloproteinase-1 linked to a glycosylphosphatidylinositol anchor
      (TIMP-1-GPI). The TIMP-1-GPI-fusion protein shows unique properties. Exogenous
      administration of TIMP-1-GPI can result in transient morphological changes to
      treated cells including modulation of proliferation and decreased resistance to
      apoptosis. The effect of TIMP-1-GPI on the biology of melanoma in the context of
      a defined hyperthermic dose was evaluated in vitro. Clonogenic assays were used
      to measure cell survival. Gelatinase zymography determined secretion of MMP-2 and
      MMP-9. Monoclonal antibody against FAS/CD95 was applied to induce apoptosis. The
      expression of pro- and anti-apoptotic proteins and the secretion of
      immunoregulatory cytokines were then evaluated using Western blot and ELISA. TIMP
      1-GPI combined with a sub-lethal hyperthermic treatment (41.8 degrees C for 2 h)
      suppressed tumor cell growth capacity as measured by clonogenic assay. The co
      treatment also significantly suppressed tumor cell proliferation, enhanced FAS
      receptor surface expression increased tumor cell susceptibility to FAS-mediated
      killing. The increased sensitivity to FAS-induced apoptosis was linked to
      alterations in the apoptotic mediators Bcl-2, Bax, Bcl-XL and Apaf-1. The agent
      works in concert with sub-lethal hyperthermic treatment to render melanoma cells
      sensitive to FAS killing. The targeted delivery of TIMP-1-GPI to tumor
      environments in the context of regional hyperthermic therapy could be optimized
      through the use of thermosensitive liposomes.

PMID- 18618110
TI  - Dendritic cell vaccination and immune monitoring.
AB  - We exploited dendritic cells (DC) to vaccinate melanoma patients. We recently
      demonstrated a statistical significant correlation between favorable clinical
      outcome and the presence of vaccine-related tumor antigen-specific T cells in
      delayed type hypersensitivity (DTH) skin biopsies. However, favorable clinical
      outcome is only observed in a minority of the treated patients. Therefore, it is
      obvious that current DC-based protocols need to be improved. For this reason, we
      study in small proof of principle trials the fate, interactions and effectiveness
      of the injected DC.

PMID- 18618111
TI  - 14-3-3 zeta protein secreted by tumor associated monocytes/macrophages from
      ascites of epithelial ovarian cancer patients.
AB  - Tumor associated monocytes/macrophages (MO/MA) are known contributors to the
      immune-inflammatory cell environment of advanced epithelial ovarian carcinoma
      (EOC). The secreted proteome of ascitic MO/MA was examined as an aid to the
      discovery of novel proteins in EOC that are likely to have biological relevance
      in the inflammatory pathways of EOC. Ascitic fluid MO/MA were isolated from EOC
      patients, grown short-term in serum-free media. MO/MA supernatants were analyzed
      for secreted proteins by HPLC fractionation followed by LC-tandem mass
      spectrometric analysis. The 14-3-3 zeta adaptor protein was identified in
      supernatants of three of three EOC patients but not in supernatants of buffy coat
      monocytes isolated from normal donors or the established monocyte cell line THP1.
      Moreover, 14-3-3 zeta was identified in ascitic fluids in eight of eight
      chemotherapy-naive patients by both immunoblot and mass spectrometric analysis.
      Immunofluorescent staining for 14-3-3 zeta demonstrated expression of the protein
      on ascitic and peritumoral macrophages in EOC patients. 14-3-3 zeta was also
      expressed on endothelial cells in the peritumoral stroma and partially on tumor
      cells. Uptake of 14-3-3 zeta was observed in EOC cell lines co-cultured with the
      recombinant protein expressed in E. coli. It is demonstrated for the first time
      that the important adaptor protein 14-3-3 zeta is common to the secretome of
      ascitic MO/MA and the ascites of advanced EOC patients.

PMID- 18618112
TI  - Lateral fixation of open AO type-B2 ankle fractures: the Knowles pin versus
      plate.
AB  - Forty-seven patients with open lateral malleolar (AO type-B2) fractures treated
      with copious irrigation and radical debridement, reduction, and immediate
      fixation by Knowles pins or lateral plates were retrospectively reviewed with an
      average follow-up period of 29 months. The 47 patients were divided into two
      groups, based on the method of treatment. The Knowles pin group included 25
      patients. The plate group included 22 patients. There was no difference between
      the Knowles pinning and lateral plating with respect to the rate of good
      reduction (96% vs. 95.5%, p = 1). Both of the groups were similar in good and
      excellent results (92% vs. 86.4%, p = 0.65). However, Knowles pinning had
      significantly shorter operation time, smaller wound size, less symptomatic
      hardware, and lower complication rate than lateral plating (all p values <0.04).
      In conclusion, lateral fixation of open AO type-B2 ankle fractures by the Knowles
      pin is recommended due to its efficacy, simplicity, and low complication rate.

PMID- 18618113
TI  - Anatomical and biomechanical evaluation of the tension band technique in patellar
      fractures.
AB  - Tension band wiring for patellar fractures is common, but some recent reports
      refer to disadvantages of this approach. Our anatomical and biomechanical study
      focused on use of tension band techniques in patellar fractures. The anatomy of
      the patella and tendon insertion was examined with knee magnetic resonance
      imaging (MRI) and correlated with the technical requirements of the tension band.
      Tension band wiring over tendinous tissue was simulated and calculated with a
      cyclic biomechanical test on cow patellae. According to tension band templating
      on the MRI section, Kirschner wire insertion was needed for the tension band to
      turn over the tendinous tissue. The tension band became more stable while turning
      over less tendinous tissue and more adjacent bone surface. Nevertheless, cyclic
      loading tests indicate that all tension band applications in this study lose
      their initial stability. Excessive initial compression by the tension band
      resulted in bending of the Kirschner wire and thus reduction failure. For optimum
      stabilisation, tension force transfer should be done directly on bone or at least
      material that protects the tendon would be useful.

PMID- 18618114
TI  - Comparison of tibial rotation in fixed and mobile bearing total knee arthroplasty
      using computer navigation.
AB  - Tibial rotation is an important aspect of knee function and can be altered after
      total knee arthroplasty (TKA). These alterations include decreased internal
      rotation with knee flexion as compared to the normal state and paradoxical
      external rotation with flexion. Mobile bearing total knee prostheses may allow
      greater unconstrained tibial rotation. I compared tibial rotation after fixed
      bearing or mobile bearing total knee arthroplasty in 82 patients who underwent
      TKA with the tibia cut first technique to ascertain any differences. Using
      intraoperative imageless computer navigation, measurements included the
      determination of tibial rotation from extension to 90 degrees flexion before and
      after prosthetic implantation with non-weight-bearing range of motion. I found
      that tibial rotation was significantly reduced after fixed bearing total knee
      replacement as compared to mobile bearing. In addition, the tibial position
      compared to the distal femur in extension was more external in fixed bearings
      compared to mobile bearings. Placing the fixed tibial tray with increased
      internal rotation could explain this difference.

PMID- 18618115
TI  - Evaluations of combination MDR-1 gene silencing and paclitaxel administration in
      biodegradable polymeric nanoparticle formulations to overcome multidrug
      resistance in cancer cells.
AB  - In this study, the effect of MDR-1 gene silencing, using small interfering RNA
      (siRNA), and paclitaxel (PTX) co-therapy in overcoming tumor multidrug resistance
      was examined. Poly(ethylene oxide)-modified poly(beta-amino ester) (PEO-PbAE) and
      PEO-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were formulated
      to efficiently encapsulate MDR-1 silencing siRNA and PTX, respectively. Upon
      administration in multidrug resistant SKOV3(TR) human ovarian adenocarcinoma
      cells, siRNA-mediated MDR-1 gene silencing was evident at 100 nM dose.
      Combination of MDR-1 gene silencing and nanoparticle-mediated delivery
      significantly influenced the cytotoxic activity of PTX in SKOV3(TR) cells similar
      to what was observed in drug sensitive SKOV3 cells. We speculate that the
      enhancement in cytotoxicity was due to an increase in intracellular drug
      accumulation upon MDR-1 gene silencing leading to an apoptotic cell-kill effect.
      Taken together, these preliminary results are highly encouraging for the
      development of combination nano-therapeutic strategies that combine gene
      silencing and drug delivery to provide more potent therapeutic effect, especially
      in refractory tumors.

PMID- 18618116
TI  - Percutaneous injection of hemostatic agents for severe blunt hepatic trauma: an
      experimental study.
AB  - This study was designed to evaluate whether percutaneous injection of hemostatic
      agents under the guidance of contrast-enhanced ultrasound (CEUS) can stop
      hemorrhage from severe hepatic trauma. Eighteen dogs were impacted by a miniature
      impactor to create blunt hepatic trauma. Fourteen with appropriate liver lesions
      were divided into two groups: the treatment group (n = 7) and the control group
      (n = 7). In the treatment group, hemocoagulase atrox and alpha-cyanoacrylate were
      respectively injected into the injury sites and transected micro-vessels under
      the guidance of CEUS. In the control group, normal saline was injected into the
      injury sites. CEUS and CT were performed at 3, 7, 14, and 21 days after the focal
      injection. Surviving animals were killed on the 21st day for pathologic
      examination. All animals of the treatment group survived. Three dogs of the
      control group died in the first 24 h. In the treatment group, CEUS and CT
      demonstrated that hepatic lesions became smaller gradually from the 3rd to the
      21st day after injection. The focal injection of hemostatic agents under the
      guidance of CEUS can stop hemorrhage from hepatic trauma of grade III~IV or IV.
      During the period of 3 weeks, no side effect was found.

PMID- 18618117
TI  - Shoulder arthroplasty.
AB  - Shoulder prostheses are now commonly used. Clinical results and patient
      satisfaction are usually good. The most commonly used types are humeral
      hemiarthroplasty, unconstrained total shoulder arthroplasty, and semiconstrained
      inversed shoulder prosthesis. Complications of shoulder arthroplasty depend on
      the prosthesis type used. The most common complications are prosthetic loosening,
      glenohumeral instability, periprosthetic fracture, rotator cuff tears, nerve
      injury, infection, and deltoid muscle dysfunction. Standard radiographs are the
      basis of both pre- and postoperative imaging. Skeletal scintigraphy has a rather
      limited role because there is overlap between postoperative changes which may
      persist for up to 1 year and early loosening and infection. Sonography is most
      commonly used postoperatively in order to demonstrate complications (hematoma and
      abscess formation) but may also be useful for the demonstration of rotator cuff
      tears occurring during follow-up. CT is useful for the demonstration of bone
      details both pre- and postoperatively. MR imaging is mainly used preoperatively,
      for instance for demonstration of rotator cuff tears.

PMID- 18618118
TI  - Training on a vascular interventional simulator: an observational study.
AB  - Radiology registrars were observed performing a left renal artery angioplasty
      using a proprietary training simulator up to five times during their first year
      of training. Total procedure time, fluoroscopy times, and metric information from
      the machine were recorded. Each step of the procedure was judged by an observer
      and a mistake profile was generated. Fifty-two runs were completed by 12
      trainees. The mean procedure time decreased from 16.6 min to 9.8 min over the
      five runs. The number of mistakes ranged from zero to ten and the mean number of
      mistakes made varied from 0.7 to 2.6 per procedure without any particular trend.
      Our study demonstrates that training on the simulator does improve performance.
      The mistakes made throughout training indicates the potential benefit from
      further simulator training. It remains unclear how to integrate this form of
      training in current educational programs.

PMID- 18618119
TI  - Patient selection guidelines in MR-guided focused ultrasound surgery of uterine
      fibroids: a pictorial guide to relevant findings in screening pelvic MRI.
AB  - Uterine leiomyomas (fibroids), the most common benign tumor in women of
      childbearing age, can cause symptoms including dysmenorrhea, menorrhagia, urinary
      symptoms, pain and infertility. Hysterectomy is a common approach to treating
      uterine fibroids, and less invasive surgical approaches such as myomectomy and
      uterine artery embolization also have been shown to alleviate symptoms. Magnetic
      resonance-guided focused ultrasound surgery (MRgFUS) is the only totally non
      invasive surgical approved method for treating uterine fibroids. In clinical
      trials, MRgFUS resulted in significant relief of uterine fibroid symptoms. The
      safe and effective use of MRgFUS is affected by fibroid type and location,
      position relative to adjacent anatomical structures and the presence of co
      existent pelvic disease. Additionally, successful outcomes with MRgFUS have been
      correlated with the volume of fibroids ablated during the procedure. Thus,
      selection of patients in whom sufficient fibroid volumes can be treated safely
      using the MRgFUS system is critical for successful outcomes. The MR images in
      this pictorial essay provide examples of uterine fibroids for which MRgFUS should
      be considered and is designed to facilitate the selection of patients for whom
      MRgFUS is most likely to provide sustained symptom relief.

PMID- 18618120
TI  - Dose reduction in dynamic perfusion CT of the brain: effects of the scan
      frequency on measurements of cerebral blood flow, cerebral blood volume, and mean
      transit time.
AB  - The influence of the frequency of computed tomography (CT) image acquisition on
      the diagnostic quality of dynamic perfusion CT (PCT) studies of the brain was
      investigated. Eight patients with clinically suspected acute ischemia of one
      hemisphere underwent PCT, performed on average 3.4 h after the onset of symptoms.
      Sixty consecutive images per slice were obtained with individual CT images
      obtained at a temporal resolution of two images per second. Eight additional data
      sets were reconstructed with temporal resolutions ranging from one image per
      second to one image per 5 s. Cerebral blood flow (CBF), cerebral blood volume
      (CBV) and mean transit time (MTT) measurements were performed in identical
      regions of interest. Two neuroradiologists evaluated the PCT images visually to
      identify areas of abnormal perfusion. Perfusion images created up to a temporal
      resolution of one image per 3 s were rated to be diagnostically equal to the
      original data. Even at one image per 4 s, all areas of infarction were
      identified. Quantitative differences of CBF, CBV and MTT measurements were < or =
      10% up to one image per 3 s. For PCT of the brain, temporal resolution can be
      reduced to one image per 3 s without significant compromise in image quality.
      This significantly reduces the radiation dose of the patient.

PMID- 18618121
TI  - Automated classification of normal and pathologic pulmonary tissue by topological
      texture features extracted from multi-detector CT in 3D.
AB  - To provide a novel, robust algorithm for classification of lung tissue depicted
      by multi-detector computed tomography (MDCT) based on the topology of CT
      attenuation values and to compare discriminative results with densitometric
      methods. Two hundred seventy-five cubic volumes of interest (VOI, edge length 40
      pixels) were obtained from MDCT chest CT (isotropic voxel size, edge length 0.6
      mm) of 21 subjects with and without pathology (emphysema, fibrosis). All VOIs
      were visually consensus-classified by two radiologists. Texture features based on
      the Minkowski functionals (MF) as well as on the CT attenuation values are
      determined. Classification results of both approaches were assessed by receiver
      operator characteristic and discriminant analysis. By densitometric (topological)
      parameters, normal and abnormal VOIs were distinguished with an area under the
      curve ranging from 0.78 to 0.85 (0.87 to 0.96). Correlation between both groups
      of parameters was non-significant (p > or = 0.36). By combined information of
      densitometric and topological quantities, the radiologists' ratings were
      reproduced for 92% of VOIs, ranging from 85.7% (fibrosis) to 98% (normal VOIs).
      Our method performs well for identification of VOIs containing abnormal lung
      tissue. Combined information of densitometry and topology increases the number of
      correctly classified VOIs further. When extended to CT data depicting whole
      lungs, topological analysis may allow to enhance density-based analysis and
      improve monitoring texture changes with progression of pulmonary disease.

PMID- 18618122
TI  - Peripheral contrast-enhanced MR angiography at 3.0T, improved spatial resolution
      and low dose contrast: initial clinical experience.
AB  - To investigate a high spatial resolution peripheral contrast-enhanced MR
      angiography (CE-MRA) protocol, applying a dedicated multi-channel array coil and
      accelerated parallel acquisition at 3.0T in evaluation of patients with
      peripheral vascular disease. Twenty patients with peripheral vascular disease
      underwent multi-station high spatial resolution peripheral CE-MRA at 3T. The
      image quality, presence of venous contamination, image noise, and artifact were
      evaluated by 2 radiologists independently. Assessment of arterial disease for 540
      arterial segments was performed, and findings were correlated with conventional
      catheter angiography in 10 patients. All studies were yielded high diagnostic
      image quality. Venous contamination and artifact were minimal and never
      interfered with diagnosis. Sixty seven arterial segments with significant
      stenoses (>0%) were detected by observers with excellent interobserver agreement
      (kappa = 0.82; 95% CI: 0.76, 0.88). There was a significant correlation between
      CE-MRA and conventional angiography (Rs = 0.91 and 0.94 for reader 1 and 2,
      respectively) for the assessment of the degree of stenosis. Higher available SNR
      at 3T in combination with multi-coil technology and accelerated parallel
      acquisition, result in acquisition of nearly isotropic submillimeter 3D voxels
      throughout the entire peripheral arterial tree with diagnostic image quality and
      favorable comparative analysis with catheter angiography.

PMID- 18618123
TI  - Cavernous malformation or cavernous hemangioma: an appropriate term to define
      liver hemangioma.

PMID- 18618124
TI  - [Topical Mitomycin C as a therapy of conjunctival tumours].
AB  - Surgical excision with tumour free margins is the gold standard for squamous cell
      and melanocytic tumours of the conjunctiva. In cases of diffuse and extensive
      tumours a complete surgical excision is sometimes not possible. Therefore,
      alternative or adjuvant therapies are required. Topical chemotherapy with
      mitomycin C (MMC) is increasingly finding use in clinical practice. MMC has
      several advantages such as good tolerability and mild side effects. Present
      studies have shown that mitomycin C is a good option in squamous cell neoplasia
      of the conjunctiva. However, further multi-centre studies and long-term follow-up
      are needed.The results in treating melanocytic tumours of the conjunctiva with
      MMC are less convincing. MMC seems to be an option for the treatment of primary
      acquired melanosis (PAM); but, if the tumour is suspicious for melanoma primary
      chemotherapy with MMC is obsolete. In these cases MMC can only be used as an
      adjuvant therapy, otherwise tumour control is not assured. However, prospective
      randomized controlled trials are necessary for a final evaluation of MMC therapy
      in melanocytic tumours of the conjunctiva.

PMID- 18618125
TI  - The spinal dermal-sinus-like stalk.
AB  - OBJECTS: In this study, a disjunction anomaly mimicking the spinal congenital
      dermal sinus (DS) is described. This anomaly is referred to as the dermal-sinus
      like stalk. Dissimilarities between a true dermal sinus and a dermal-sinus-like
      stalk are discussed. CLINICAL MATERIAL: Three cases in which a spinal congenital
      dermal sinus was suspected are presented. A similar anatomical configuration,
      different from that of a dermal sinus, was found. All cases presented with a skin
      covered dimple from which a solid tract was seen continuing intramedullary in two
      cases and intraspinally in one case. None of the patients presented with signs of
      infection or an associated dermoid-epidermoid tumor. Clinical, radiological, and
      surgical findings are discussed. A hypothesis is made on the pathological genesis
      of this malformation. CONCLUSION: A dermal-sinus-like stalk is a malformation
      similar to a spinal congenital dermal sinus but is not associated with DS-related
      complications. Despite important clinical, radiological, surgical, and
      histopathological differences, it is difficult to distinguish this malformation
      from a true DS based on clinical and radiological examination alone. Therefore,
      surgical intervention, at the time of diagnosis, is recommended in all cases.

PMID- 18618127
TI  - Subfoveal choroidal neovascularization complicating 25-gauge trans-retinal
      choroidal tumor biopsy.

PMID- 18618126
TI  - Primary vitrectomy with Densiron-68 for rhegmatogenous retinal detachment.
AB  - BACKGROUND: To report a retrospective non-comparative interventional study on the
      effectiveness and ocular tolerance of a heavy silicone oil tamponade (HSO,
      Densiron-68) for primary inferior rhegmatogenous retinal detachment (RRD).
      METHODS: Forty-one eyes of 41 consecutive patients were recruited between January
      2004 and August 2006. Primary vitrectomy with Densiron-68, a heavy silicone oil,
      was used in all cases. Inclusion criteria were primary RRD with at least one
      retinal break between 4 and 8 clock hours. The study protocol consisted of a
      minimum of eight clinic visits: baseline, surgery, 1 week, 1 month and 3 months
      after the initial surgery; removal of oil and 1 week, 1 month and 3 months
      postoperatively. The primary endpoint was anatomical re-attachment of the retina.
      Cases were judged successful when there was reattachment of the retina in the
      absence of any tamponade agent. The secondary endpoint was to record the visual
      function and any complications arising from the surgery. Out of 41 patients
      initially included in the study, 33 completed all follow-up visits. RESULTS:
      Anatomical success was achieved in 91% of cases (30 out of 33) with one retinal
      operation, and rose to 94% (31 out of 33) with additional surgery. Mean visual
      acuity improved from logMAR 1.19 (SD 0.9) to 0.5 (SD 0.51, p = 0.001). No
      significant ocular hypertension, clinically significant emulsification of the
      tamponade or inflammation developed during follow-up. CONCLUSION: With Densiron
      68, high anatomical and functional success rates can be achieved with primary
      vitrectomy for RRD and predominantly inferior pathology.

PMID- 18618128
TI  - Histological assessment of cellular half-life in tissues in vivo.
AB  - The assessment of cellular half-life is of fundamental importance for cell
      biology and biomedicine. Here, we show that cellular half-life in tissues can be
      histologically measured under steady state conditions in vivo by analyzing the
      loss of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells over time after withdrawal
      of long-term BrdU labeling. To achieve efficient continuous cell labeling, we
      implanted BrdU-containing subcutaneous slow-release pellets into 12-month-old
      male Fischer 344 rats, delivering BrdU at a dose of 75 mg/kg per day over 1
      (n=20) or 3 weeks (n=20). Four to five rats each were killed directly after the
      labeling or 1, 3, and 7 weeks post-labeling. Cellular half-life after withdrawal
      of BrdU was analyzed by nonlinear regression analysis of the labeling index,
      using a model of one-phase exponential decay. We initially validated our
      technique in the duodenum, where we determined a half-life of 2.4 days for crypt
      cells. Next, we applied this method to other tissues, and found a half-life of
      2.2 weeks for cardiac endothelial cells, and of 5-6 days for pancreatic duct
      cells. In conclusion, we believe that this novel approach is an important step
      forward in the histological assessment of cellular half-life.

PMID- 18618129
TI  - MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for
      molecular histology.
AB  - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry
      (IMS) is a powerful tool for investigating the distribution of proteins and small
      molecules within biological systems through the in situ analysis of tissue
      sections. MALDI-IMS can determine the distribution of hundreds of unknown
      compounds in a single measurement and enables the acquisition of cellular
      expression profiles while maintaining the cellular and molecular integrity. In
      recent years, a great many advances in the practice of imaging mass spectrometry
      have taken place, making the technique more sensitive, robust, and ultimately
      useful. In this review, we focus on the current state of the art of MALDI-IMS,
      describe basic technological developments for MALDI-IMS of animal and human
      tissues, and discuss some recent applications in basic research and in clinical
      settings.

PMID- 18618130
TI  - Distribution of prolyl oligopeptidase in the mouse whole-body sections and
      peripheral tissues.
AB  - Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyses proline
      containing peptides shorter than 30-mer, including many bioactive peptides. The
      distribution of POP in the brain has been studied but little is known about the
      distribution of peripheral POP. We used immunohistochemistry to localize POP in
      mouse whole-body sections and at the cellular level in peripheral tissues.
      Furthermore, we used a POP activity assay to reveal the associations between POP
      protein and its enzymatic activity. The highest POP protein densities were found
      in brain, kidney, testis and thymus, but in the liver the amounts of POP protein
      were small. There were remarkable differences between the distribution of POP
      protein and activity. The highest POP activities were found in the liver and
      testis while kidney had the lowest activity. In peripheral tissues, POP was
      present in various cell types both in the cytoplasm and nucleus of the cells, in
      contrast to the brain where no nuclear localization was detected. These findings
      support the proposed role of POP in cell proliferation in peripheral tissues. The
      dissociation of the distribution of POP protein and its enzymatic activity points
      to nonhydrolytic functions of POP and to strict endogenous regulation of POP
      activity.

PMID- 18618131
TI  - Use of dual section mRNA in situ hybridisation/immunohistochemistry to clarify
      gene expression patterns during the early stages of nephron development in the
      embryo and in the mature nephron of the adult mouse kidney.
AB  - The kidney is the most complex organ within the urogenital system. The adult
      mouse kidney contains in excess of 8,000 mature nephrons, each of which can be
      subdivided into a renal corpuscle and 14 distinct tubular segments. The
      histological complexity of this organ can make the clarification of the site of
      gene expression by in situ hybridisation difficult. We have defined a panel of
      seven antibodies capable of identifying the six stages of early nephron
      development, the tubular nephron segments and the components of the renal
      corpuscle within the embryonic and adult mouse kidney. We have analysed in detail
      the protein expression of Wt1, Calb1 Aqp1, Aqp2 and Umod using these antibodies.
      We have then coupled immunohistochemistry with RNA in situ hybridisation in order
      to precisely identify the expression pattern of different genes, including Wnt4,
      Umod and Spp1. This technique will be invaluable for examining at high
      resolution, the structure of both the developing and mature nephron where
      standard in situ hybridisation and histological techniques are insufficient. The
      use of this technique will enhance the expression analyses of genes which may be
      involved in nephron formation and the function of the mature nephron in the
      mouse.

PMID- 18618133
TI  - Do we really need a central governor to explain brain regulation of exercise
      performance?
AB  - In this paper two different models of brain regulation of exercise performance
      are critically compared: the central governor model proposed by Noakes and
      colleagues, and an alternative psycholobiological model based on motivational
      intensity theory.

PMID- 18618132
TI  - Limiting factors in peak oxygen uptake and the relationship with functional
      ambulation in ambulating children with spina bifida.
AB  - The objective of this study is to interpret the outcomes of peak oxygen uptake
      (VO(2peak)) in children with SB and explore the relationship between VO(2peak)
      and functional ambulation using retrospective cross-sectional study. Twenty-three
      ambulating children with SB participated at Wilhelmina's Children's Hospital
      Utrecht, the Netherlands. VO(2peak) was measured during a graded treadmill-test.
      Eschenbacher's and Maninna's algorithm was used to determine limiting factors in
      reaching low VO(2peak) values. Energy expenditure during locomotion (both O(2)
      rate and O(2) cost) and percentage of VO(2peak) and HR(peak) were determined
      during a 6-min walking test (6MWT). Differences between community and normal
      ambulators were analyzed. VO(2peak), VO(2peak)/kg, HR(peak), RER(peak) and VE
      (peak) were significantly lower compared to reference values, with significant
      differences between normal and community ambulators. Limiting factors according
      to the algorithm were mostly "muscular and/or deconditioning" (47%) and
      ventilatory "gasexchange" (35%). Distance walked during 6MWT was 48.5% of
      predicted distance. Both O(2) rate and O(2) cost were high with significant
      differences between normal and community ambulators [17.6 vs. 21.9 ml/(kg min)
      and 0.27 vs 0.43 ml/(kg m)]. Also %HR(peak) and %VO(2peak) were significantly
      higher in community ambulators when compared to normal ambulators (resp. 97.6 vs.
      75% and 90.2 vs. 55.9%). VO(2peak) seems to be mostly limited by deconditioning
      and/or muscular components and possible ventilatory factors. For both peak values
      and functional ambulation, community ambulators were significantly more impaired
      than normal ambulators. High energy expenditure, %VO(2peak) and %HR(peak) reflect
      high level of strain during ambulation in the community ambulators. Future
      exercise testing in children with SB should include assessment of ventilatory
      reserve. Exercise training in ambulatory children should focus on increasing both
      VO(2peak) and muscular endurance, as well as decreasing energy cost of
      locomotion.

PMID- 18618134
TI  - Does a central governor regulate maximal exercise during combined arm and leg
      exercise? A rebuttal.

PMID- 18618135
TI  - Mechanomyographic responses in quadriceps muscles during fatigue by continuous
      cycle exercise.
AB  - The present study examined whether the mechanomyogram (MMG) could assess the
      fatigue-related changes in muscle mechanical properties during cycle exercise. In
      eight male subjects, the MMG signals were measured in vastus lateralis and rectus
      femoris by electret condenser microphones. It was found that the integrated MMG
      (iMMG) showed non linear increase against workload during continuous, incremental
      cycle exercise and the onset of abrupt changes in iMMG coincided with the
      ventilatory threshold (VT). Specifically, iMMG in vastus lateralis showed a
      significant decrement in the rate of increase against workload above VT,
      reflecting the fatigue-induced impairment of contractile properties of the fibers
      of active motor units. These results suggest that the MMG measured by electret
      condenser microphone could be practically used to retrieve the fatigue-related
      changes in muscle mechanical properties during cycle exercise.

PMID- 18618136
TI  - Postural trials: expertise in rhythmic gymnastics increases control in lateral
      directions.
AB  - The first aim of this paper was to investigate if expertise in rhythmic
      gymnastics influences postural performance even in an easy non-specific task such
      as bipedal posture. Rhythmic gymnastics is a unique female sport which
      encompasses aspects of both artistic gymnastics and ballet and includes the use
      of a small apparatus (rope, hoop, ball, clubs and ribbon). Most previous studies
      have shown that expertise achieved by artistic gymnasts and dancers improves
      postural steadiness only in the situations for which those athletes are trained.
      Literature has not yet compared rhythmic gymnasts to other athletes in terms of
      their postural strategies. Hence, the study presented herein tested a group of
      high level rhythmic gymnasts and a group of female university students, trained
      in other sports, in the bipedal posture under eyes open and closed conditions. A
      force platform was used to record body sway. (1) Distance from the centre of
      sway, (2) lateral and (3) antero-posterior displacements were analyzed in time
      and frequency domains. Comparing the two groups, it was found that rhythmic
      gymnasts had better strategies than students in simple postural tasks, especially
      in lateral directions and in the period from 0.05 to 2 s. The most interesting
      finding in this study is that rhythmic gymnastics training seems to have a direct
      effect on the ability to maintain bipedal posture, which may confirm the
      "transfer" hypothesis of rhythmic gymnastics expertise to bipedal postural sway,
      especially in medio-lateral displacements. This finding has never been reported
      in previous studies on artistic gymnasts and ballet dancers. Furthermore, the
      present study confirmed the visual dependence of all the athletes, irrespective
      of their disciplines, in their postural trials.

PMID- 18618137
TI  - A comparison of the effects of milk and a carbohydrate-electrolyte drink on the
      restoration of fluid balance and exercise capacity in a hot, humid environment.
AB  - Following a 2.0 +/- 0.1% body mass loss induced by intermittent exercise in the
      heat, seven male volunteers ingested either a carbohydrate-electrolyte solution
      (CE) or skimmed milk (M) in a volume equal to 150% of body mass loss. At the end
      of the 3 h recovery period, subjects were essentially in positive fluid balance
      on trial M (191 +/- 162 mL), and euhydrated on trial CE (-135 +/- 392 mL) despite
      being in negative sodium balance on both trials and negative potassium balance on
      trial CE. This difference of 326 +/- 354 mL or 0.4% body mass approached
      significance (P = 0.051). Subjects ingested 137 +/- 15 and 113 +/- 12 g of CHO
      during the CE and M trials, respectively, as well as 75 +/- 8 g of protein during
      the M trial. At the end of the 3 h recovery period, an exercise capacity test was
      completed at 61% VO(2peak) in warm (35.3 +/- 0.5 degrees C), humid (63 +/- 2%)
      conditions. HR (P = 0.020) and rectal temperature (P = 0.045) were higher on
      trial M, but no difference in exercise time to exhaustion was observed between
      trials (39.6 +/- 7.3 min vs. 39.7 +/- 8.1 min on trials CE and M, respectively).
      The results of the present study suggest that milk can be an effective post
      exercise rehydration drink, with subjects remaining in net positive fluid balance
      throughout the recovery period. Despite the effect on fluid retention, exercise
      capacity was not different between skimmed milk and a commercially available
      carbohydrate-electrolyte drink 4 h following exercise/heat-induced body mass
      loss.

PMID- 18618138
TI  - Serum 1-84 and 7-84 parathyroid hormone concentrations and bone in patients with
      primary hyperparathyroidism.
AB  - BACKGROUND AND AIMS: Parathyroid hormone (PTH) acts on bone as both anabolic and
      catabolic factor. It includes two fractions: 1-84 (cyclase activating PTH, CAP)
      which increases bone turnover and serum calcium, and 7-84 (cyclase inactivating
      PTH, CIP) acting the opposite way. The aim of this study was to establish whether
      bone mineral density (BMD) and turnover in patients' primary hyperparathyroidism
      (HPT) are dependent on CAP and CIP concentrations. PATIENTS/METHODS: Thirty-one
      patients with HPT and 29 appropriately matched controls were examined. Parameters
      of calcium-phosphate homeostasis and BMD were estimated. RESULTS: BMD of radius
      shaft was lower in patients with HPT as compared with controls, whereas BMD of
      spine and ultradistal radius were similar. Serum calcium, bone alkaline
      phosphatase, total PTH, 1-84 PTH, and 7-84 PTH were higher in HPT patients,
      whereas serum phosphate was lower and beta cross-laps similar. Both total PTH and
      CAP correlated significantly with BMD of radius shaft and serum calcium
      concentration, but not with other examined parameters. CONCLUSION: Total and 1-84
      PTH are similarly associated with examined parameters in patients with HPT. Thus,
      determination of serum CAP concentration does not seem to have advantages over
      total PTH with regard to bone mineral density and bone turnover assessment in
      those patients.

PMID- 18618139
TI  - Endocrine surgery.

PMID- 18618140
TI  - Severe hypothyroidism after contrast enema in premature infants.
AB  - Premature newborns are particularly vulnerable to iatrogenic hypothyroidism due
      to iodine exposure, usually through skin absorption of iodine-containing
      disinfectants or intravenous administration of iodinated contrast agents. We
      report here a case of severe iatrogenic hypothyroidism with goiter and
      cholestasis, discovered six weeks after a contrast enema using sodium
      ioxitalamate, an iodinated contrast agent. Prematurity, intrauterine growth
      retardation, and enteral feeding intolerance could explain why this complication
      occurred after contrast enema. Our observations suggest that indications of
      contrast enema in neonates need to be carefully considered, and when necessary,
      thyroid function should be monitored, especially in very premature infants.

PMID- 18618141
TI  - Molecular characterization of the DYX1C1 gene and its application as a cancer
      biomarker.
AB  - PURPOSE: DYX1C1 has three alternatively spliced transcripts. Therefore, we expect
      that alternative transcripts of DYX1C1 are used as a biomarker to detect specific
      cancer. METHODS: RT-PCR analysis is conducted in order to detect expression of
      the DYX1C1 gene and the PCR products were analyzed using the Image J program to
      compare the expression levels of each transcript. RESULTS: We found one of the
      transcripts was directly associated with an HERV-H LTR element that could be
      translated into protein sequence. Four new alternative transcripts were
      identified by RT-PCR analysis with various human tissue samples including 10
      normal and adjacent tumor tissue sets. Semi-quantitative RT-PCR analysis showed
      the transcriptional activity of V3 and V2 was higher in tumor than in normal
      tissue samples, especially in the colorectal tissue samples. CONCLUSION: Our
      results indicated that alternatively spliced transcript variants of the DYX1C1
      gene could be used as cancer biomarkers to detect colorectal cancer.

PMID- 18618142
TI  - Sex difference in the influence of smoking status on the responsiveness to
      gefitinib monotherapy in adenocarcinoma of the lung: Okayama Lung Cancer Study
      Group experience.
AB  - BACKGROUND: Gefitinib is effective in patients with lung adenocarcinoma. Smoking
      status also affects the responsiveness to gefitinib, but it has not been fully
      evaluated whether a sex difference exists in the influence of smoking on the
      efficacy of gefitinib in patients with lung adenocarcinoma. METHODS: We reviewed
      the clinical records of 260 Japanese patients with lung adenocarcinoma who
      received gefitinib therapy (250 mg/day), and whose smoking status was known.
      Tumour response and survival were evaluated and stratified by smoking status and
      gender. RESULTS: Among the 260 patients, 157 were male (60%). Median pack-years
      was 40 (range 8-160) and 23 (range 1-74) in male and female smokers,
      respectively. Objective response was observed in 62 (23.8%) of the 260 patients,
      and 1-year overall survival and progression-free survival were 45.1 and 24.3%,
      respectively. Multivariate analysis revealed that smoking status (pack-years) was
      an independent predictive factor for response to gefitinib [odds ratio (OR) =
      0.971, 95% confidence interval (CI) = 0.947-0.995; P = 0.0159] in male patients,
      but not in female patients (OR = 0.999, 95%CI = 0.957-1.042). Additionally, pack
      years significantly influenced the overall survival in males (hazard ratio =
      1.010; 95%CI = 1.002-1018, P = 0.0169), while differential survival of females
      was not significantly predicted by this factor (P = 0.7639). CONCLUSIONS: In male
      patients with lung adenocarcinoma, cumulative smoking significantly affected
      response and survival following gefitinib treatment, while in female patients,
      responsiveness to gefitinib was independent of smoking status. These results
      suggest that the influence of smoking habit on responsiveness to gefitinib is
      gender specific.

PMID- 18618143
TI  - Diagnosis of Babesia caballi and Theileria equi infections in horses in Sudan
      using ELISA and PCR.
AB  - The purpose of this study was to estimate the prevalence of equine piroplasmosis
      in Sudan. The presence of antibodies against Babesia caballi and Theileria equi
      was determined in serum samples obtained from 158 horses raised in different
      locations in Sudan by enzyme-linked immunosorbent assay (ELISA). The B. caballi
      48-kDa and the T. equi EMA-2 purified recombinant proteins were used as antigens
      in the ELISA test. Results showed that seven (4.4%) were positive for B. caballi
      and 80 (63.5%) were positive for T. equi. Polymerase chain reaction (PCR) assays
      have been applied using primers targeting the B. caballi 48-kDa merozoite
      antigen, the T. equi SSUrRNA and the T. equi EMA-1 genes. PCR performed on 131
      blood spots in filter paper revealed that 33 (25.2%) samples were positive for T.
      equi but no positives were found for B. caballi. It is concluded that equine
      piroplasmosis is endemic in the country. This is the first study on serological
      and molecular epidemiological diagnosis on equine piroplasmosis in Sudan.

PMID- 18618144
TI  - Isolation of Ani s 5, an excretory-secretory and highly heat-resistant allergen
      useful for the diagnosis of Anisakis larvae sensitization.
AB  - Allergens Ani s 1 and Ani s 4 have demonstrated their utility for the diagnosis
      of the sensitization to larvae of the genus Anisakis. The aim was to determine
      the number of patients with compatible clinical history, who did not recognize
      Ani s 1 and Ani s 4, and characterize the allergens responsible for their
      sensitization. Eighty-four patients were studied by CAP and immunoglobulin E
      (IgE) immunoblotting. The 12% of the patients recognized allergens different from
      Ani s 1 and Ani s 4, being half sensitized to a heat-resistant 15-kDa allergen,
      which was isolated by ethanol fractionation, followed by a hydroxyapatite
      chromatography and a reversed-phase high-performance liquid chromatography and
      identified by its amino terminal sequence as Ani s 5. A total of 41 of the 84
      patients studied (49%) showed specific IgE to Ani s 5 that was detected among the
      excretory-secretory products and immunohistochemically located at the excretory
      gland, ventriculus, and the luminal surface of the intestinal epithelium of the
      larvae.

PMID- 18618145
TI  - Acanthamoeba spp. cysts storage in filter paper.
AB  - A new method of storage of the free-living amoeba, Acanthamoeba, is described.
      For this purpose, strips of filter paper were impregnated with cysts of amoebas
      cultivated axenically and transferred into a cryotube. The strips were dehydrated
      at 30 degrees C for 24 h and after storage at room temperature. The amoeba
      viability has been evaluated and the cysts remain viable and pure for at least 1
      year. Then, our method has been efficient for the storage of cysts during the
      evaluated period.

PMID- 18618146
TI  - Use of the FLOTAC technique for the diagnosis of Aelurostrongylus abstrusus in
      the cat.
AB  - Aelurostrongylus abstrusus is a lungworm of the domestic cats distributed
      worldwide. Its presence, however, is often underestimated due to limitation of
      common coprological diagnostic techniques. The present study reports, for the
      first time, the use of the FLOTAC technique for A. abstrusus diagnosis in feline
      faecal samples with results compared to the following three standard
      copromicroscopic techniques: the Baermann technique, the McMaster technique and
      the Wisconsin technique. The comparison study showed that the FLOTAC technique
      produced mean larvae per gram of faeces significantly (P<0.05) greater than that
      produced by the other more widely used diagnostic tools. Thus, the FLOTAC
      technique can be utilised for quantifying lungworm larva burdens in feline faecal
      samples because of its high sensitivity, as already shown for various parasites
      of veterinary and human importance.

PMID- 18618147
TI  - The differentiation of transcription between tachyzoites and bradyzoites of in
      vitro cultured Neospora caninum.
AB  - Interconversion between tachyzoites and bradyzoites of Neospora caninum plays a
      pivotal role in transmission of the parasite. Although significant efforts have
      been made toward understanding the mechanisms that trigger and control stage
      conversion of the parasite, little is known about this process. We used annealing
      control primer (ACP)-based polymerase chain reaction (PCR) technique to
      characterize the differences in transcription between tachyzoites and bradyzoites
      of N. caninum. The in vitro stage conversion of N. caninum-infected Vero cells
      was induced by treatment of infected cultures with 70 microM sodium
      nitroprusside. Subsequently, the gene expression profiles of the tachyzoites and
      bradyzoites were analyzed through comparison of the level of messenger RNA
      expression. ACP-based PCR revealed 85 amplicons that were consistently
      differentially expressed between tachyzoite and bradyzoite stages. Of the 85
      differentially expressed transcripts identified, ten were cloned into Topo TA
      cloning vector, sequenced, and further analyzed by the Basic Local Alignment
      Search Tool. These differentially expressed transcripts include a combination of
      known genes and as yet unidentified genes. The present work provides candidate
      genes for further investigation on molecular basis of stage conversion from
      tachyzoites to bradyzoites of N. caninum.

PMID- 18618148
TI  - Feeding sustains photosynthetic quantum yield of a scleractinian coral during
      thermal stress.
AB  - Thermal resistance of the coral-zooxanthellae symbiosis has been associated with
      chronic photoinhibition, increased antioxidant activity and protein repair
      involving high demands of nitrogen and energy. While the relative importance of
      heterotrophy as a source of nutrients and energy for cnidarian hosts, and as a
      means of nitrogen acquisition for their zooxanthellae, is well documented, the
      effect of feeding on the thermal sensitivity of the symbiotic association has
      been so far overlooked. Here we examine the effect of zooplankton feeding versus
      starvation on the bleaching susceptibility and photosynthetic activity of
      photosystem II (PSII) of zooxanthellae in the scleractinian coral Stylophora
      pistillata in response to thermal stress (daily temperature rises of 2-3 degrees
      C) over 10 days, employing pulse-amplitude-modulated chlorophyll fluorometry. Fed
      and starved corals displayed a decrease in daily maximum potential quantum yield
      (F (v)/F (m)) of PSII, effective quantum yield (F/F (m)') and relative electron
      transport rates over the course of 10 days. However after 10 days of exposure to
      elevated temperature, F (v)/F (m) of fed corals was still 50-70% higher than F
      (v)/F (m) of starved corals. Starved corals showed strong signs of chronic
      photoinhibition, which was reflected in a significant decline in nocturnal
      recovery rates of PSII relative to fed corals. This was paralleled by the
      progressive inability to dissipate excess excitation energy via non-photochemical
      quenching (NPQ). After 10 days, NPQ of starved corals had decreased by about 80%
      relative to fed corals. Feeding treatment had no significant effect on
      chlorophyll a and c (2) concentrations and zooxanthellae densities, but the
      mitotic indices were significantly lower in starved than in fed corals.
      Collectively the results indicate that exogenous food may reduce the
      photophysiological damage of zooxanthellae that typically leads to bleaching and
      could therefore play an important role in mediating the thermal resistance of
      some corals.

PMID- 18618149
TI  - Identifying the predator complex of Homalodisca vitripennis (Hemiptera:
      Cicadellidae): a comparative study of the efficacy of an ELISA and PCR gut
      content assay.
AB  - A growing number of ecologists are using molecular gut content assays to
      qualitatively measure predation. The two most popular gut content assays are
      immunoassays employing pest-specific monoclonal antibodies (mAb) and polymerase
      chain reaction (PCR) assays employing pest-specific DNA. Here, we present results
      from the first study to simultaneously use both methods to identify predators of
      the glassy winged sharpshooter (GWSS), Homalodisca vitripennis (Germar)
      (Hemiptera: Cicadellidae). A total of 1,229 arthropod predators, representing 30
      taxa, were collected from urban landscapes in central California and assayed
      first by means of enzyme-linked immunosorbent assay (ELISA) using a GWSS egg
      specific mAb and then by PCR using a GWSS-specific DNA marker that amplifies a
      197-base pair fragment of its cytochrome oxidase gene (subunit I). The gut
      content analyses revealed that GWSS remains were present in 15.5% of the
      predators examined, with 18% of the spiders and 11% of the insect predators
      testing positive. Common spider predators included members of the Salticidae,
      Clubionidae, Anyphaenidae, Miturgidae, and Corinnidae families. Common insect
      predators included lacewings (Neuroptera: Chrysopidae), praying mantis (Mantodea:
      Mantidae), ants (Hymenoptera: Formicidae), assassin bugs (Hemiptera: Reduviidae),
      and damsel bugs (Hemiptera: Nabidae). Comparison of the two assays indicated that
      they were not equally effective at detecting GWSS remains in predator guts. The
      advantages of combining the attributes of both types of assays to more precisely
      assess field predation and the pros and cons of each assay for mass-screening
      predators are discussed.

PMID- 18618150
TI  - Prediction of high-degree steroid dependency in pediatric idiopathic nephrotic
      syndrome.
AB  - Most patients with idiopathic nephrotic syndrome are steroid-responsive, but
      about 50% relapse and often become steroid-dependent and exposed to long-term
      steroid complications. The aim of this study was to determine predictive risk
      factors for steroid and/or cyclosporine A (CyA) dependence. In France, steroid
      responsiveness is defined as remission after 1 month of oral prednisone (60
      mg/m(2) per day) and-in the case of persistent proteinuria on day 30-three
      methylprednisolone pulses (MPP; 1 g/1.73 m(2) on days 1, 3, and 5). Thirty-five
      steroid-responsive children, followed between 1999 and 2006, were included in
      this study. Median age at diagnosis was 4.9 years. All patients initially
      received prednisone 60 mg/m(2) per day. Twenty-four of the 35 patients were
      steroid-dependent, with 12 requiring MPP. Of the latter 12 patients, 83.3% were
      treated with CyA during follow-up; in comparison, only 16.7% of the patients who
      did not receive MPP required CyA during follow-up (chi-square test, P = 0.001). T
      risk for steroid dependence was 100% in our cohort if remission was achieved
      after day 20. Patients who need MPP are at high risk to require CyA to achieve
      disease control. By identifying these children, we could use adequate
      immunosuppressive drugs earlier and reduce morbidity related to steroids and
      multiple relapses.

PMID- 18618151
TI  - Protective effect of Epo on oxidative renal injury in rats with cyclosporine
      nephrotoxicity.
AB  - The aim of our study was to determine the effect of recombinant human
      erythropoietin (rhEPO) on cyclosporine (CsA) nephrotoxicity. Twenty-six female
      Wistar rats were injected with 15 mg/kg subcutaneous CsA and intraperitoneal
      saline/rhEPO for 28 days. Four groups were formed: Group 1 (n = 5), a control
      group; Group 2 (n = 7), CsA + saline; Group 3 (n = 7), CsA + low dose (20 U/kg
      per day) rhEPO; Group 4 (n = 7), CsA + high dose (100 U/kg per day) rhEPO. Body
      weights, creatinine clearance, urinary protein/creatinine, hematocrit, serum
      creatinine levels, histopathological parameters, apoptosis and lipid peroxidation
      tests were compared between the three groups. Body weights and renal functions
      were similar in Groups 2, 3 and 4 rats but significantly lower than the values
      found for the control group at the end of the study. The hematocrit was
      significantly different between the four groups, showing a positive association
      with the strength of the injected rhEPO doses. Tubular and arteriolar damage was
      significantly lower in Groups 3 and 4 rats than in Group 2 rats, while chronic
      changes were similar between the three groups. TUNEL-positive cells and
      thiobabarbituric acid reacting substance (TBARS) levels were significantly higher
      in Group 2 rats, whereas superoxide dismutase levels were significantly lower in
      Group 2 rats than in those of the other three groups. Low or high dose rhEPO had
      no significant protective effects on body weight, renal functions, chronic
      fibrotic changes, but both doses reduced tubular and arteriolar changes,
      apoptotis and oxidative stress.

PMID- 18618152
TI  - Correlation between large-scale atmospheric fields and the olive pollen season in
      Central Italy.
AB  - Olives are one of the largest crops in the Mediterranean and in central and
      southern Italy. This work investigates the correlation of the Olea europaea L.
      pollen season in Perugia, the capital city of the region of Umbria in central
      Italy, with atmospheric parameters. The aim of the study is twofold. First, we
      study the correlation between the pollen season and the surface air temperature
      of the spring and late spring in Perugia. Second, the correlation between the
      pollen season and large-scale atmospheric patterns is investigated. The average
      surface temperature in the spring and late spring has a clear impact on the
      pollen season in Perugia. Years with higher average temperatures have an earlier
      onset of the pollen season. In particular, a 1 degrees C higher (lower) average
      surface temperature corresponds to an earlier (later) start of the pollen season
      of about 1 week. The correlation between the pollen season and large-scale
      atmospheric patterns of sea level pressure and 500-hPa geopotential height shows
      that the cyclonic activity in the Mediterranean is unequivocally tied to the
      pollen season in Perugia. A larger than average cyclonic activity in the
      Mediterranean Basin corresponds to a later than average pollen season. Larger
      than average cyclonic activity in Northern Europe and Siberia corresponds to an
      earlier than average pollen season. A possible explanation of this correlation,
      that needs further investigation to be proven, is given. These results can have a
      practical application by using the seasonal forecast of atmospheric general
      circulation models.

PMID- 18618153
TI  - Pharmacophore mapping of a series of pyrrolopyrimidines, indolopyrimidines and
      their congeners as multidrug-resistance-associated protein (MRP1) modulators.
AB  - Pharmacophore mapping studies were undertaken for a series of molecules belonging
      to pyrrolopyrimidines, indolopyrimidines and their congeners as multidrug
      resistance-associated protein (MRP1) modulators. A five-point pharmacophore with
      two hydrogen bond acceptors (A), one lipophilic/hydrophobic group (H), one
      positive ionic feature (P) and one aromatic ring (R) as pharmacophoric features
      was developed. The pharmacophore hypothesis yielded a statistically significant
      3D-QSAR model, with a correlation coefficient of r2 = 0.799 for training set
      molecules. The model generated showed excellent predictive power, with a
      correlation coefficient Q2 = 0.679 for an external test set of 20 molecules. The
      pharmacophore was further validated using four structurally diverse compounds
      with MRP1 modulatory activity. These compounds mapped well onto four of the five
      features of the pharmacophore. The pharmacophore proposed here was then utilised
      for the successful retrieval of active molecules with diverse chemotypes from
      database search. The geometry and features of pharmacophore are expected to be
      useful for the design of selective MRP1 inhibitors.

PMID- 18618154
TI  - Cellular interaction through LewisX cluster: theoretical studies.
AB  - It is well known that cell surface carbohydrates play a role in cell-cell
      adhesion and communication. LewisX glycosphingolipids form microdomains on cell
      surfaces. Homotypic and calcium-mediated LewisX-LewisX (LeX-LeX) interactions
      were proposed to be responsible for the initial steps of cell adhesion, and to
      mediate embryogenesis and metastasis. Various techniques have been used to
      investigate such interactions, but little information is available on the
      geometry and the mechanism of dimerisation. To better understand these
      interactions, a new molecular model was developed to simulate homotypic
      interactions in explicit solvent with and without calcium ions. Accurate analysis
      of both trajectories yielded valuable information about the energetics of LeX-LeX
      dimerisation. Detailed interpretation of the hydrogen bond network and the
      presence of calcium ions along the trajectory provide valuable insights into the
      role of calcium ions in this carbohydrate-carbohydrate interaction.

PMID- 18618155
TI  - Using a multiplex polymerase chain reaction for the identification of Beijing
      strains of Mycobacterium tuberculosis.
AB  - The genotype of a Beijing strain of Mycobacterium tuberculosis (MTB) is usually
      determined by spoligotyping. However, this technique requires special equipment
      and is time-consuming. In this study, we developed a new multiplex polymerase
      chain reaction (PCR) to differentiate between Beijing and non-Beijing strains of
      MTB. A total of 323 MTB isolates were genotyped by both spoligotyping and the
      novel multiplex PCR. By spoligotyping, 169 (52.3%) isolates were determined to be
      Beijing strains and the remaining 154 (47.7%) isolates were non-Beijing strains.
      The multiplex PCR method produced results identical to those of spoligotyping in
      the identification of Beijing strains of MTB. This method is highly sensitive,
      specific, and fast. It is also cost-effective and suitable for screening large
      numbers of samples.

PMID- 18618156
TI  - Effectiveness of a vaccination program against mumps in Ukraine.
AB  - Medical records and incidence data were analyzed retrospectively to document the
      epidemiology, clinical features, and outcomes of mumps in relation to vaccination
      status in the Lviv province of Ukraine over a 7.5-year period, beginning in 2000,
      when a second dose of mumps vaccine was introduced. Lviv, 1 of 27 provinces in
      western Ukraine, with a land area of 21,833 km(2), had a total population of
      about 2,555,834 in 2006. The initial success of the second dose introduction in
      2000 in Ukraine was limited by a local outbreak of mumps in Lviv province in 2000
      2002 due to a vaccine shortage; most cases were over the age of 7 years. The
      vaccine with the Leningrad-3 virus strain used before 2001 was then replaced by
      the triple vaccine "Priorix", with the RIT 4385 derivate of the Jeryl Lynn
      strain, Belgium. Orchitis and aseptic meningitis were associated with the Russian
      vaccine. Of the 10,894 reported cases, the most severe (367 cases, 3.4%) were
      hospitalized in the Lviv Hospital for Infectious Diseases. Admitted patients were
      predominantly male and over 14 years old. Of the 367 patients admitted to the
      Lviv Hospital for Infectious Diseases, 45.8% had been vaccinated (mostly by a
      first dose of Russian vaccine), 15.9% had not been vaccinated, and 38.1% had an
      unknown vaccination status. More mumps cases occurred in winter and spring than
      in summer and autumn. The clinical picture and complications (orchitis,
      pancreatitis, meningitis, and encephalitis) were typical of this disease. The
      vaccine shortage and an increase in the susceptible population among those who
      received the Russian vaccine contributed to the outbreak. The use of vaccine with
      a derivate of the Jeryl Lynn strain has resulted in a dramatic drop in mumps
      cases since 2002.

PMID- 18618158
TI  - Guidelines for completing the EURONHEED transferability information checklists.
AB  - The structure and methods to complete and derive a quality score from the
      European Network of Health Economic Evaluation Databases (EURONHEED)
      transferability information checklists for published economic evaluations were
      reported and discussed in a previous paper (Boulenger et al. in Eur J Health Econ
      6, 334-346, 2005). Within the same paper, the use of the checklists was
      illustrated through their application to a sample of economic evaluations
      conducted in France and UK. The transferability information subchecklist,
      consisting of 16 items from the original 42-point checklist, and methods used to
      derive it, were validated among 16 health economists across Europe participating
      in the EURONHEED project. Recent correspondence with other researchers, however,
      indicates that the checklists are now being utilised in empirical work and the
      methodology of assessing transferability and generalisability. This supplementary
      paper provides full details of the guidelines that have been developed and
      recently updated by the authors, such that the overall and subchecklists can be
      more widely and consistently completed and utilised. We also briefly discuss
      associated issues such as weighting of items in the checklists and give further
      clarifications regarding what we consider the most appropriate applications of
      the checklists to be.

PMID- 18618157
TI  - Possible involvement of interferon beta in post-operative vasculitis restricted
      to the tumour bed: a case report.
AB  - Cerebral vasculitis is a very rare complication after brain tumour surgery. We
      herein report a case and discuss the origins of this complication. A 52-year-old
      female was admitted because of motor aphasia due to a left frontal lobe brain
      tumour. The magnetic resonance imaging (MRI) study revealed a non-enhanced
      tumour. A partial resection of the tumour and the placement of an Ommaya's
      reservoir were performed. The pathological diagnosis was an oligoastrocytoma. The
      patient recovered well without any neurological deficits. Post-operative
      radiotherapy and the intravenous injection of interferon beta were performed.
      During these treatments, the patient showed a continued high fever. An MRI scan
      revealed multiple enhanced lesions in the residual tumour, thus raising
      suspicions about a post-operative infection. We therefore performed a tumour
      biopsy and the removal of the exogenous materials. The histopathological
      diagnosis was vasculitis in the residual tumour. The patient's consciousness and
      neurological symptoms recovered quickly with the steroid treatment. Following the
      radiotherapy (50 Gy total), complete remission of the tumour was rapidly obtained
      and no recurrence was observed. Cerebral vasculitis confined to the tumour bed is
      an unusual complication; however, this special condition was of critical
      importance for a successful tumour regression in this patient.

PMID- 18618159
TI  - GraPHIA: a computational model for identifying phonological jokes.
AB  - Currently in humor research, there exists a dearth of computational models for
      humor perception. The existing theories are not quantifiable and efforts need to
      be made to quantify the models and incorporate neuropsychological findings in
      humor research. We propose a new computational model (GraPHIA) for perceiving
      phonological jokes or puns. GraPHIA consists of a semantic network and a
      phonological network where words are represented by nodes in both the networks.
      Novel features based on graph theoretical concepts are proposed and computed for
      the identification of homophonic jokes. The data set for evaluating the model
      consisted of homophonic puns, normal sentences, and ambiguous nonsense sentences.
      The classification results show that the feature values result in successful
      identification of phonological jokes and ambiguous nonsense sentences suggesting
      that the proposed model is a plausible model for humor perception. Further work
      is needed to extend the model for identification of other types of phonological
      jokes.

PMID- 18618161
TI  - Objective video quality measure for application to tele-echocardiography.
AB  - Real-time tele-echocardiography is widely used to remotely diagnose or exclude
      congenital heart defects. Cost effective technical implementation is realised
      using low-bandwidth transmission systems and lossy compression
      (videoconferencing) schemes. In our study, DICOM video sequences were converted
      to common multimedia formats, which were then, compressed using three lossy
      compression algorithms. We then applied a digital (multimedia) video quality
      metric (VQM) to determine objectively a value for degradation due to compression.
      Three levels of compression were simulated by varying system bandwidth and
      compared to a subjective assessment of video clip quality by three paediatric
      cardiologists with more than 5 years of experience.

PMID- 18618162
TI  - A computational study on the biomechanical factors related to stent-graft models
      in the thoracic aorta.
AB  - Endovascular aortic stent-graft is a new, minimally invasive procedure for
      treating thoracic aortic diseases, and has quickly evolved to be one of the
      standard treatments subject to anatomic constraints. This procedure involves the
      placement of a self-expanding stent-graft system in a high-flow thoracic aorta.
      Stent-graft deployment in the thoracic aorta, especially close to the aortic
      arch, normally experiences a significant drag force which might lead to the risk
      of stent-graft failure. A comprehensive investigation on the biomechanical
      factors affecting the drag force on a stent-graft in the thoracic aorta is thus
      in order, and the goal is to perform an in-depth study on the contributing
      biomechanical factors. Three factors affecting the deployed stent-graft are
      considered, namely, the internal diameter of the vessel, the starting position of
      the graft and the diameter of curvature of the aortic arch. Computational fluid
      dynamic techniques are applied to model the blood flow. The inlet velocity and
      outlet pressure are assumed to be pulsatile. The three-dimensional continuity
      equation and the time-dependent Navier-Stokes equations for an incompressible
      fluid were solved numerically. The drag force due to the change of momentum
      within the stent-graft and the shear stress were calculated and analyzed. The
      drag force on a stent-graft will depend critically on the internal diameter and
      the starting position of stent-graft deployment. Larger internal diameter leads
      to larger drag force and the stent-graft deployed at the more distal position may
      be associated with significantly diminished drag force. Smaller diameter of
      curvature of the aortic arch probably results in a decline of the drag force on
      the stent-graft, even though this factor merely causes only a modest difference.
      These findings may have important implications for the choice and design of stent
      grafts in the future.

PMID- 18618163
TI  - Evaluation and treatment of oral candidiasis in HIV/AIDS patients in Enugu,
      Nigeria.
AB  - INTRODUCTION: Oral candidiasis is one of the common diseases seen in HIV/AIDS
      patients. It is rare if CD4+ cell counts are above 500 microl. Outbreaks are more
      common as the count drops to 100 microl. It may be more difficult to treat when
      CD4+ cell counts fall below 50 microl. MATERIALS AND METHODS: A retrospective
      review of 112 HIV/AIDS patients with lesions in the mouth, head, and neck seen at
      the oral and maxillofacial surgery units of two public hospitals in eastern
      Nigeria was carried out between 2000 and 2003. The focus was on oral candidiasis
      patients. Twenty-nine of these patients, made up of 11 males and 18 females, had
      oral candidiasis. To compare the action of two drugs, namely, nystatin (a topical
      antifungal drug) and ketoconazole (a systemic antifungal drug), we treated 15 of
      the patients with nystatin in the first 2 years and the remaining 14 with
      ketoconazole in the following 2 years. RESULTS AND DISCUSSION: Amongst the 15
      patients treated with topical drugs, 7 (46.7%) had complete remission, 2 (13.3%)
      had partial response, 4 (26.7%) remained stationary, and 2 (13.3%) died. Out of
      the 14 cases treated with systemic drugs, 11 (78.6%) had complete remission, 2
      (14.3%) had partial response, and 1 (7.1%) died.

PMID- 18618164
TI  - Healing patterns of critical size bony defects in rat following bone graft.
AB  - PURPOSE: The aim of the present study was to evaluate the healing patterns of
      critical size calvarial bony defects treated with different bone substitutes and
      to compare them to an autogenous graft and an ungrafted control group. MATERIALS
      AND METHODS: Thirty-six Sprague-Dawley rats (200-230 g) were used. A periosteal
      flap was raised and an 8 mm defect was trephined. Rats were divided into six
      groups and treated as follows: group 1 was treated with a deproteinized bovine
      xenograft (XO), group 2 was treated with a bovine xenograft and covered with a
      resorbable membrane (XOCM), defects in group 3 were filled with a decalcified
      freeze-dried bone allograft (DFDBA), group 4 was treated with a composite bone
      substitute made of bovine xenograft and collagen (XOC), group 5 was filled with
      autogenous bone (AUTO), and group 6 was left untreated (control). The animals
      were euthanized at 2 months. RESULTS: Mean bone formation was 2.97 +/- 1.82 mm2
      in group 5 (AUTO) followed by 2.93 +/- 1.93 mm2 in group 3 (DFDBA) and 2.25 +/-
      1.94 mm2 in group 4 (XOC). Groups 1, 2, and 6 (XO, XOCM, and control,
      respectively) were not significantly different (p > 0.05) with a mean bone
      formation of 1.97 +/- 1.64, 1.87 +/- 1.07, and 1.85 +/- 1.04 mm2, respectively.
      CONCLUSIONS: This work confirmed the superiority of autogenous bone when it comes
      to bone grafting. Nevertheless, some bone substitutes can improve bone formation
      when compared to the control. New bone substitutes with growth factors to improve
      their abilities to induce bone formation should be experimented.

PMID- 18618165
TI  - Prospective closed treatment of nondisplaced and nondislocated condylar neck and
      head fractures versus open reposition internal fixation of displaced and
      dislocated fractures.
AB  - OBJECTIVE: assessment of open reduction internal fixation in displaced or
      dislocated fractures of the condylar neck and head assessed versus closed
      treatment of nondisplaced, nondislocated fractures. MATERIALS AND METHODS: One
      hundred and twenty patients suffering from 158 fractures; classes II to V
      according to Spiessl and Schroll, e.g., displaced and dislocated fractures were
      operated on; classes I and VI nondisplaced, nondislocated fractures were treated
      conservatively. At 1year, facial symmetry, pain, facial nerve function, and
      scarring were assessed clinically; reossification and fragment angulation were
      assessed from radiographs; vertical position, incisal maximum movements, and
      condyle translation were judged by millimeters. RESULTS AND DISCUSSION: Clinical
      courses were uncomplicated in classes I to IV and did reach horizontal and
      vertical fragment reposition with minor remodeling in follow-up. Single cases
      evinced persistent pain, dysocclusion, facial nerve palsy, and plate fractures.
      Results were less successful in classes V and VI: although open reposition
      internal fixation showed good repositioning in class V, marked vertical bone
      remodeling occurred; single cases suffered from pain, dysocclusion, and plate
      fracture. Class VI cases had the worst translation, likewise marked condyle
      remodeling, and frequent dysocclusion. CONCLUSION: Classes V and VI remain
      challenging to treat, while the other classes can be treated reliably with this
      study's rationale. Condyle remodeling in classes V and VI, translation in class
      VI may benefit prospectively from even more careful mobilization, improved
      osteofixation as minimalized operation trauma.

PMID- 18618166
TI  - Gene expression of nestin, collagen type I and type III in human dental follicle
      cells after cultivation in serum-free medium.
AB  - BACKGROUND: Undifferentiated human dental cells and especially human dental
      follicle cells are interesting for potential dental treatments. These somatic
      stem cells are cultured usually in cell culture medium containing bovine serum.
      In the age of bovine spongiform encephalopathy (BSE), a serum-free cell culture
      system for dental follicle cells are recommended, if these cells will be applied
      in dentistry. PURPOSE: However, less is known about the cultivation of dental
      follicle cells in serum-replacement medium. In this study, we cultivated dental
      follicle cells in serum-free cell culture medium, which is normally applied for
      neuronal stem/progenitor cells. MATERIALS AND METHODS: Dental follicle cells were
      cultivated in both serum-free and serum-containing cell culture media, and gene
      expression profiles were recorded for connective tissue markers collagen type I
      and type III and for the human dental follicle cell marker nestin. RESULTS: It is
      interesting to note that the gene expressions of collagens and nestin were
      similar after applying both cell culture conditions. CONCLUSION: Although the
      gene expression of dental follicle cell markers was unchanged, a more appropriate
      serum-free cell culture medium is recommended for cell proliferation of dental
      follicle cells.

PMID- 18618167
TI  - Bilateral maxillary brown tumours as the first presentation of primary
      hyperparathyroidism.
AB  - INTRODUCTION: Symptomatic skeletal disease in primary hyperparathyroidism is over
      30 times more common in India compared to the west. The classical "brown tumour"
      is commonly seen with the major sites being ends of long bones, the pelvis and
      ribs. Facial involvement is rare and, when present, usually involves the
      mandible. CASE REPORT: We report a 68-year-old gentleman with a rare initial
      presentation of primary hyperparathyroidism with bilateral maxillary brown
      tumours. DISCUSSION AND CONCLUSION: Successful parathyroid surgery resulted in a
      regression in the tumours. The report highlights the need to consider primary
      hyperparathyroidism in the initial differential diagnosis of bony lesions of the
      jaw.

PMID- 18618168
TI  - Presence of cholesterol granuloma in the maxillary and ethmoid sinuses.
AB  - INTRODUCTION: Although cholesterol granuloma associated with chronic middle ear
      disease is shown to be common in the mastoid antrum and air cells of the temporal
      bone (Leon et al., Arch Pathol Lab Med 126:217-219, 2002), its presence in the
      maxillary and ethmoid sinuses is rarely encountered. There are few cases reported
      regarding the incidence of cholesterol granuloma in these sinuses (Ko et al., Am
      J Otoryngol 27:370-372, 2006). CASE: Here, we report a case of concomitant
      cholesterol granuloma in the maxillary and ethmoid sinuses of a 33-year-old man
      who underwent surgical excision. DISCUSSION: Histopathological examination of the
      removed specimen revealed fragments of respiratory mucosa with cholesterol clefts
      surrounded by multinucleated foreign-body giant cells.

PMID- 18618172
TI  - Integration of wireless sensor networks into cyberinfrastructure for monitoring
      Hawaiian "mountain-to-sea" environments.
AB  - Monitoring the complex environmental relationships and feedbacks of ecosystems on
      catchment (or mountain)-to-sea scales is essential for social systems to
      effectively deal with the escalating impacts of expanding human populations
      globally on watersheds. However, synthesis of emerging technologies into a robust
      observing platform for the monitoring of coupled human-natural environments on
      extended spatial scales has been slow to develop. For this purpose, the authors
      produced a new cyberinfrastructure for environmental monitoring which
      successfully merged the use of wireless sensor technologies, grid computing with
      three-dimensional (3D) geospatial data visualization/exploration, and a secured
      internet portal user interface, into a working prototype for monitoring mountain
      to-sea environments in the high Hawaiian Islands. A use-case example is described
      in which native Hawaiian residents of Waipa Valley (Kauai) utilized the
      technology to monitor the effects of regional weather variation on surface water
      quality/quantity response, to better understand their local hydrologic cycle,
      monitor agricultural water use, and mitigate the effects of lowland flooding.

PMID- 18618173
TI  - Negative effects of low temperatures on the vertical transmission and infection
      density of a spiroplasma endosymbiont in Drosophila hydei.
AB  - Maternally transmitted endosymbionts of the genus Spiroplasma infecting several
      species of Drosophila are known to cause selective death of male offspring (male
      killing). The male-killing trait is considered to be advantageous for maternally
      transmitted endosymbionts. However, a non-male-killing spiroplasma is present in
      Japanese populations of Drosophila hydei at high frequencies (23-66%). This
      spiroplasma is phylogenetically closely related to the male-killing spiroplasma
      infecting other Drosophila species. It is unknown why this spiroplasma is
      maintained in its host populations despite its inability to cause male killing.
      We examined the susceptibilities of the spiroplasma in D. hydei to four different
      temperatures (28, 25, 18, and 15 degrees C). Diagnostic PCR revealed that
      vertical transmission of the spiroplasma was nearly perfect at 28 and 25 degrees
      C, partially suppressed at 18 degrees C, and completely blocked at 15 degrees C.
      Furthermore, quantitative PCR demonstrated that offspring treated at 18 degrees C
      exhibited dramatically lower densities of spiroplasma (i.e., approximately one
      tenth) compared to offspring treated at 28 and 25 degrees C. Considering the low
      temperatures during winter in Japan, some unknown advantageous effects of the
      spiroplasma that compensate for the failure of vertical transmission are
      suggested to act in natural populations of D. hydei.

PMID- 18618174
TI  - Insights into two high homogenous genes involved in copper homeostasis in
      Acidithiobacillus ferrooxidans.
AB  - Acidithiobacillus ferrooxidans, an important microorganism in bioleaching
      industry, has been sequenced recently, and from the annotated information, there
      are four genes involved in copper homeostasis. Sequence analysis showed that two
      of them, Afe0329 and Afe0663, were high homologous (94.43% identity). With the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      cloning approach, the differential gene expression of these two high homologous
      genes in a genome was successfully identified for the first time. In comparison
      with Afe0663, Afe0329 was highly expressed grown in the medium with copper, and
      the restriction fragment length polymorphism (RFLP) profile showed that 96% of
      lanes were products of Afe0329. Analysis of the protein sequence encoded by
      Afe0329 suggested a conserved domain of P1b3-type ATPase, which is a heavy-metal
      pump, and, to be unexpected, the molecular modeling revealed that the amino acids
      determining the type of heavy-metal pumps were responsible for the gate of the
      copper ion channel in the transmembrane area of the protein. The activity of P1b
      type ATPase disrupted in Escherichia coli could be partially rescued by
      complementation by the plasmid-carrying Afe0329 gene. All of these results
      suggest that a copper homeostasis mechanism including P-type ATPase is of
      importance for the survival of this extremophilic microorganism.

PMID- 18618175
TI  - Mycobacterium tuberculosis antigen Wag31 induces expression of C-chemokine XCL2
      in macrophages.
AB  - Tuberculosis is still a major threat to human health. To date, only approximately
      half of the proteins encoded by Mycobacterium tuberculosis H37Rv have been
      assigned specific functions. Wag31 (Rv2145c) is one of the bacterial proteins
      whose function is mostly unknown. Using a modified split-ubiquitin membrane yeast
      two-hybrid system, we screened a macrophage cDNA library with Wag31 as bait and
      identified XCL2, a C-subfamily chemokine, as a binding partner for Wag31. More
      importantly, Wag31 was found to specifically stimulate XCL2 expression in
      macrophages. The results from this study demonstrate that expression of C
      chemokine is not restricted to certain types of T cells and natural killer cells.
      Because C-chemokine is chemotactic for CD8+ and CD4+ T cells, our novel findings
      could provide a new mechanism by which the bacteria induce cell-mediated immunity
      and by which Wag31 could be a potential target for controlling M. tuberculosis
      infection.

PMID- 18618176
TI  - Dysphagia due to unilateral infarction in the vascular territory of the anterior
      insula.
AB  - We describe a patient who suddenly developed dysphagia for liquids as the sole
      manifestation of stroke. Magnetic resonance imaging (MRI) revealed a right-sided
      infarction of the superior part of the anterior insula and a small portion of the
      adjacent medial frontal operculum. These findings confirm the role of the
      anterior insula as a critical area in humans with regard to the origin of
      dysphagia.

PMID- 18618177
TI  - Effect of reduced stereoscopic camera separation on ring placement with a
      surgical telerobot.
AB  - BACKGROUND: A custom, stereoscopic video camera was built to study the impact of
      decreased camera separation on a stereoscopically viewed, visual-manual task
      resembling some aspects of surgery. MATERIALS AND METHODS: Twelve naive subjects
      and one of the experimenters were first trained in a ring placement task using
      the stereo-laparoscope and subsequently switched to the stereo-camera, which was
      used with differing camera separations ranging from 100% of the laparoscope's
      separation to a biocular view corresponding to no separation (2D). RESULTS: The
      results suggest firstly, that stereopsis (i.e., use of 3D laparoscopes) improves
      surgical performance over conventional 2D laparoscopes, and secondly that camera
      separation may be reduced 20-35% without appreciably degrading user performance.
      Even a 50% reduction in separation resulted in stereoscopically supported
      performance far superior compared to the 2D condition. CONCLUSIONS: The results
      suggest that existing 3D laparoscopes which use 5-mm camera separation may well
      be significantly miniaturized without causing substantial performance
      degradation.

PMID- 18618178
TI  - Chrysomelidial in the opisthonotal glands of the oribatid mite, Oribotritia
      berlesei.
AB  - Gas chromatographic-mass spectrometric analyses of whole body extracts of
      Oribotritia berlesei, a large-sized soil-dwelling oribatid mite, revealed a
      consistent chemical pattern of ten components, probably originating from the well
      developed opisthonotal glands. The three major components of the extract were the
      iridoid monoterpene, (3S,8S)-chrysomelidial (about 45% of the extract), the
      unsaturated hydrocarbon 6,9-heptadecadiene, and the diterpene beta-springene (the
      latter two, each about 20-25% of the extract). The remaining minor components
      (together about 10% of the extract) included a series of hydrocarbons (tridecene,
      tridecane, pentadecene, pentadecane, 8-heptadecene, and heptadecane) and the
      tentatively identified 9,17-octadecadienal. In contrast, analysis of juveniles
      showed only two compounds, namely a 2:1 mixture of (3S,8S)-chrysomelidial and its
      epimer, epi-chrysomelidial (3S,8R-chrysomelidial). Unexpectedly, neither adult
      nor juvenile secretions contained the so-called astigmatid compounds, which are
      considered characteristic of secretions of oribatids above moderately derived
      Mixonomata. The chrysomelidials, as well as beta-springene and octadecadienal,
      are newly identified compounds in the opisthonotal glands of oribatid mites and
      have chemotaxonomic potential for this group. This is the first instance of
      finding chrysomelidials outside the Coleoptera.

PMID- 18618179
TI  - Barrett's esophagus (BE) and carcinoma in the esophageal stump (ES) after
      esophagectomy with gastric pull-up in achalasia patients: a study based on 10
      years follow-up.
AB  - BACKGROUND: Subtotal esophagectomy and gastric pull-up with cervical anastomosis
      is the main treatment for advanced achalasia. This surgical technique has been
      associated to esophagitis and also Barrett's epithelium following esophagectomy.
      AIM: To analyze late clinical, endoscopic, and pathologic findings in the
      esophageal stump (ES) mucosa after subtotal esophagectomy in patients treated for
      advanced chagasic achalasia. METHODS: 101 patients submitted to esophagectomy and
      cervical gastroplasty were followed-up prospectively for a mean of 10.5 +/- 8.8
      years. All patients underwent clinical, endoscopic and histopathological
      evaluation every 2 years. Gastric acid secretion was also assessed. RESULTS: The
      incidence of esophagitis in the esophageal stump (45.9% at 1 year; 71.9% at 5
      years, and 70.0% at 10 years follow-up); gastritis in the transposed stomach
      (20.4% at 1 year, 31.0% at 5 years, and 40.0% at 10 or more years follow-up), and
      the occurrence of ectopic columnar metaplasia and Barrett's Esophagus in the ES
      (none until 1 year; 10.9% between 1 and 5 years; 29.5% between 5 and 10 years;
      and 57.5% at 10 or more years follow-up), all rose over time. Gastric acid
      secretion returns to its preoperative values 4 years postoperatively. Esophageal
      stump cancer was detected in the setting of chronic esophagitis in five patients:
      three squamous cell carcinomas and two adenocarcinomas. CONCLUSION: (1)
      Esophagitis and Barrett's esophagus in the esophageal stump rose over time. (2)
      These mucosal alterations and the development of squamous cell carcinoma and
      adenocarcinoma are probably due to exposure to duodenogastric reflux, and
      progressively higher acid output in the transposed stomach.

PMID- 18618180
TI  - Predictors of surgical margin status in breast-conserving surgery within a breast
      screening program.
AB  - BACKGROUND: Breast-conserving surgery (BCS) requires clear surgical margins to
      minimize local recurrence. We sought to identify groups of patients at higher
      risk of involved margins who might benefit from preoperative counselling and/or
      more generous excision at the first operation. METHODS: We reviewed demographic,
      clinical, radiological and pathological records of all women diagnosed with
      ductal carcinoma in situ (DCIS) or invasive cancer (IC) through a population
      based breast screening program in Melbourne, Australia between 1994 and 2005.
      RESULTS: A total of 2,160 women were diagnosed with DCIS or IC. We excluded 199
      who had mastectomy (TM) as initial procedure or had missing data. Three hundred
      and thirteen had a diagnostic biopsy. Of 1,648 women who had BCS after a
      preoperative diagnosis of DCIS or IC, 13.5% had involved margins, 16.6% had close
      (</=1 mm), and 69.8% clear (>1 mm) margins. Of the patients, 281/1,648 (17.1%)
      underwent re-excision, of whom 93 (33.1%) had residual disease identified.
      Mammographic microcalcifications (P < 0.0001), absence of a mammographic mass (P
      = 0.002), presence of DCIS (P < 0.0001), high tumour grade (P < 0.0001), large
      size (P < 0.0001), multifocal disease (P < 0.0001) and lobular histology (P =
      0.005) were associated with involved margins. Microcalcifications (odds ratio
      [OR] 1.97), large size (OR 4.22) and multifocal disease (OR 2.85) were
      independently associated with involved margins. Residual disease was associated
      with involved margins (P < 0.0001), presence of DCIS (P = 0.05) and large tumour
      size (P = 0.01). CONCLUSION: After BCS, patients with mammographic
      microcalcifications, larger tumour size and multifocal tumours are more likely to
      have involved margins. Patients with involved margins, large tumour size and/or a
      DCIS component are more likely to have residual disease on re-excision.

PMID- 18618181
TI  - Intersphincteric resection for very low rectal adenocarcinoma: univariate and
      multivariate analyses of risk factors for recurrence.
AB  - BACKGROUND: The aim of this study was to analyze the risk factors for local and
      distant recurrence after intersphincteric resection (ISR) for very low rectal
      adenocarcinoma. METHODS: One hundred twenty consecutive patients with T1-T3
      rectal cancers located 1-5 (median 3) cm from the anal verge underwent ISR.
      Univariate and multivariate analyses of prospectively recorded clinicopathologic
      parameters were performed. RESULTS: Fifty patients had disease categorized as
      stage I, 21 as stage II, 46 as stage III, and 3 as stage IV on the basis of
      International Union Against Cancer tumor, node, metastasis staging system. Median
      follow-up time was 3.5 years. The 3-year rates of local and distant recurrence
      were 6% and 13%, respectively. Univariate analysis of the risk factors for local
      recurrence revealed pathologic T, pathologic stage, focal dedifferentiation,
      microscopic resection margins, and preoperative serum CA 19-9 level to be
      statistically significant. Multivariate analysis showed resection margin, focal
      dedifferentiation, and serum CA 19-9 level to be independently significant.
      Univariate analysis of the risk factors for distant recurrence indicated tumor
      location, combined resection, tumor annularity, pathologic N, lateral pelvic
      lymph node metastasis, pathologic stage, histologic grade, lymphovascular
      invasion, perineural invasion, and adjuvant chemotherapy to be significant.
      Multivariate analysis identified pathologic N, histologic grade, and tumor
      location to be independently significant. CONCLUSION: Profiles of risk factors
      for local and distant recurrences after ISR are different. With local recurrence,
      the resection margin, focal dedifferentiation, and serum CA 19-9 level are
      important. For distant recurrence, the lymph node status, histologic grade, and
      tumor location need to be taken into account.

PMID- 18618182
TI  - Local recurrence after laparoscopic radiofrequency ablation of liver tumors: an
      analysis of 1032 tumors.
AB  - BACKGROUND: The best measure of the technical success of radiofrequency ablation
      (RFA) is local recurrence (LR). The aim of this prospective study is to identify
      factors that predict LR. METHODS: Three hundred thirty-five patients with 1032
      unresectable liver tumors underwent laparoscopic RFA between November 1999 and
      August 2005. All lesions were assessed prospectively regarding tumor type, size,
      liver segment, blood vessel proximity, and central or peripheral location in the
      operating room and size of ablation zone at 1-week computed tomographic (CT)
      scans. Lesions that recurred in follow-up CT scans were identified prospectively.
      LR was categorized as contiguous or adjacent. Univariate Kaplan-Meier and Cox
      proportional hazard models were used for statistical analysis. RESULTS: LR was
      identified 21.7% of tumors on CT scans with a mean follow-up of 17 months
      (median, 12 months; range, 3-68 months). This was contiguous in 70% and adjacent
      in 30%. LR rate per tumor was highest for colorectal metastasis (34%), followed
      by noncolorectal, nonneuroendocrine metastasis (22%), hepatocellular carcinoma
      (18%), and neuroendocrine metastasis (6%). By univariate analysis, tumor type and
      size, ablation margin, liver segmental location, blood vessel proximity, and type
      of ablation (first time vs. repeat) were found to affect LR. The Cox proportional
      hazard model identified tumor type, tumor size, ablation margin, and blood vessel
      proximity to be independent predictors of LR. CONCLUSION: LR after RFA is
      predicted by certain tumor characteristics and technical factors. This
      information can be used intraoperatively to identify those tumors at a higher
      risk for failure.

PMID- 18618183
TI  - Analysis of clinical applicability of the breast cancer nomogram for positive
      sentinel lymph node: the canadian experience.
AB  - BACKGROUND: A Breast Cancer Nomogram (BCN) for predicting nonsentinel lymph node
      (NSLN) involvement has been developed and prospectively tested in several series.
      However, its clinical applicability has never been tested among surgeons.
      METHODS: The BCN was applied to 209 SLN-positive patients. Its performance was
      assessed by the area under the receiver-operating characteristic (ROC) curve.
      Surgeons in Quebec were surveyed to determine the predicted NSLN positivity below
      which they would not dissect the axilla. The accuracy of the BCN was determined
      in this clinically relevant range. RESULTS: The predictive accuracy of the BCN
      had an area under the ROC curve of 0.687. Almost half of interviewed surgeons
      treat over 20 breast cancer per year. Fourteen out of 82 surgeons questioned
      would never leave the patient without a completion axillary dissection after a
      positive SLN, regardless of the BCN result. Seventy one percent of them would not
      complete axillary dissection if the prediction of a positive NSLN was </=10%.
      Only 37 of the 209 patients were in this 10% or less category, with a mean
      observed rate of positive NSLN of 13% (95% confidence interval [CI], 2-24%).
      CONCLUSION: The global performance of the BCN was fair. A majority of surgeons in
      Quebec would omit an axillary lymph node dissection (ALND) if the predicted
      probability of positive NSLN is 10% or less. Although useful, the BCN data should
      be used with caution at the low end of the scale. Because of some limitations in
      the performance in this category, other clinical factors and judgment must
      accompany its use.

PMID- 18618184
TI  - Screening for or prevention of local ipsilateral recurrence and contralateral
      breast cancer after breast-conserving surgery?

PMID- 18618185
TI  - Combined axillary reverse mapping (ARM) technique for breast cancer patients
      requiring axillary dissection.
AB  - BACKGROUND: The objective of axillary reverse mapping (ARM) is to preserve the
      main lymphatic chain-with both the nodes and the ducts-in relation to lymphatic
      arm drainage (LAD) during an axillary dissection (AD). METHODS: From July 2006 to
      March 2008, 23 patients with stage II or III breast carcinoma requiring an AD
      underwent an ARM procedure. Identification of the ARM nodes relied on an isotope
      injection into the web space of the ipsilateral hand. During AD, the radioactive
      ARM node was localized above the second intercostal brachial nerve, and blue dye
      was directly injected inside the node to visualize the efferent ducts,
      constituting the lymphatic ARM chain. The blue and radioactive nodes constituted
      the ARM sampling, while other nodes were considered part of the AD. RESULTS:
      Metastatic lymph node involvement was identified in the AD in 20 of 23 patients,
      with an average of 4.4 (1-11) nodes involved and an average of 10.7 (7-20) lymph
      nodes removed. The ARM sampling was performed in 21 of 23 patients (91%), with an
      average of 1.6 ARM nodes removed. In 18 of these 21 patients (86%), the nodes
      relating to ARM sampling had no metastatic involvement. There were 3 patients
      (14%) who demonstrated metastatic involvement of the ARM sampling, and all had
      pN3a (N+ > 9) involvement of the axilla. CONCLUSION: This technique of combined
      isotopic and blue dye ARM and findings must now be validated. A multicentric
      study is planned to confirm this data.

PMID- 18618186
TI  - Laparoscopic-assisted proctectomy for rectal cancer: on trial.

PMID- 18618187
TI  - Menopausal hormone therapy and breast cancer phenotype: does dose matter?
AB  - BACKGROUND: Duration and type of menopausal hormone therapy (HT) has been
      associated with increased breast cancer risk and the development of estrogen
      receptor (ER)-positive tumors. The effect of HT dose on breast cancer tumor
      characteristics remains undefined. We sought to determine if HT dosing regimens
      influence breast cancer phenotype. METHODS: We conducted a retrospective review
      of incident female breast cancers occurring in the year 2003 listed in the Kaiser
      Permanente Northern California Cancer Registry. Type of HT, dose, number of
      tablets dispensed, tumor phenotype, stage, grade, and histology were obtained
      from electronic records for women aged >/=50 years who had more than 1 year of
      uninterrupted pharmacy data (n = 1701). A dose index of HT exposure was created
      and odds ratios were used to determine if tumor phenotype varied between exposure
      groups. These results were compared with a previously published analysis of HT
      duration on tumor phenotype conducted with the same dataset. RESULTS: The
      cumulative effect of estrogen and progesterone hormone therapy as calculated by
      factoring both dose and duration of HT use prior to breast cancer diagnosis did
      not reveal any new associations that were not previously identified by analysis
      of HT duration of exposure alone. Low-dose-index combination-HT users were less
      likely to have tumors with an ER-positive phenotype. An overall trend developed
      in which low- and high-dose-index exposed women had the lowest rates of ER- and
      progesterone receptor (PR) -positive tumors. CONCLUSION: Duration of use is an
      adequate surrogate for determining overall exposure to HT when considering the
      effect of HT on breast cancer phenotype.

PMID- 18618188
TI  - Laparoscopic partial adrenalectomy for bilateral pheochromocytomas.
AB  - BACKGROUND: Patients with hereditary pheochromocytoma are at risk of the
      development of bilateral disease. Partial adrenalectomy can preserve adrenal
      function to avoid the morbidity associated with medical adrenal replacement.
      Here, we report a multimedia case study of synchronous bilateral partial
      adrenalectomy by the laparoscopic approach. METHODS: A 13-year-old patient with
      von Hippel-Lindau disease was found to have high urinary metanephrines and
      normetanephrines. Computed tomography showed bilateral adrenal tumors (2.5 cm on
      the right side and 0.9 cm on the left). MIBG scan showed positive uptake in the
      right adrenal gland without extra-adrenal uptake. After adequate adrenergic
      blockade, the patient underwent laparoscopic partial adrenalectomy bilaterally.
      RESULTS: The left side was approached first with the patient in the right
      decubitus position. Intraoperative ultrasound was performed to determine the line
      of tumor excision, which was carefully planned to preserve most of the normal
      appearing gland. Both tumors were excised completely with good hemostasis. The
      main adrenal veins of both sides were precisely preserved. Operative time was 228
      minutes. No clinically important hemodynamic fluctuations were noted. Pathologic
      examination confirmed bilateral entirely excised pheochromocytomas. The patient
      has not required exogenous corticosteroid replacement at follow-up. CONCLUSION:
      Laparoscopic partial adrenalectomy for bilateral pheochromocytomas is safe and
      technically feasible. It should be considered the treatment of choice for
      hereditary pheochromocytoma.

PMID- 18618189
TI  - Does outpatient telephone coaching add to hospital quality improvement following
      hospitalization for acute coronary syndrome?
AB  - BACKGROUND: Telephone counseling in chronic disease self-management is
      increasing, but has not been tested in studies that control for quality of
      medical care. OBJECTIVE: To test the effectiveness of a six-session outpatient
      telephone-based counseling intervention to improve secondary prevention
      (behaviors, medication) in patients with acute coronary syndrome (ACS) following
      discharge from hospital, and impact on physical functioning and quality of life
      at 8 months post-discharge. DESIGN: Patient-level randomized trial of hospital
      quality improvement (QI-only) versus quality improvement plus brief telephone
      coaching in three months post-hospitalization (QI-plus). DATA: medical record,
      state vital records, patient surveys (baseline, three and eight months post
      hospitalization). ANALYSIS: pooled-time series generalized estimating equations
      to analyze repeated measures; intention-to-treat analysis. PARTICIPANTS: Seven
      hundred and nineteen patients admitted to one of five hospitals in two contiguous
      mid-Michigan communities enrolled; 525 completed baseline surveys. MEASUREMENTS:
      We measured secondary prevention behaviors, physical functioning, and quality of
      life. RESULTS: QI-plus patients showed higher self-reported physical activity (OR
      = 1.53; p = .01) during the first three months, with decline after active
      intervention was withdrawn. Smoking cessation and medication use were not
      different at 3 or 8 months; functional status and quality of life were not
      different at 8 months. CONCLUSIONS: Telephone coaching post-hospitalization for
      ACS was modestly effective in accomplishing short-term, but not long-term life
      style behavior change. Previous positive results shown in primary care did not
      transfer to free-standing telephone counseling as an adjunct to care following
      hospitalization.

PMID- 18618190
TI  - Healthcare workplace conversations on race and the perspectives of physicians of
      African descent.
AB  - BACKGROUND: Although experts recommend that healthcare organizations create
      forums for honest dialogue about race, there is little insight into the physician
      perspectives that may influence these conversations across the healthcare
      workforce. OBJECTIVE: To identify the range of perspectives that might contribute
      to workplace silence on race and affect participation in race-related
      conversations within healthcare settings. DESIGN: In-person, in-depth, racially
      concordant qualitative interviews. PARTICIPANTS: Twenty-five physicians of
      African descent practicing in the 6 New England states. APPROACH: Line-by-line
      independent coding and group negotiated consensus to develop codes structure
      using constant comparative method. MAIN RESULTS: Five themes characterize
      perspectives of participating physicians of African descent that potentially
      influence race-related conversations at work: 1) Perceived race-related
      healthcare experiences shape how participating physicians view healthcare
      organizations and their professional identities prior to any formal medical
      training; 2) Protecting racial/ethnic minority patients from healthcare
      discrimination is a top priority for participating physicians; 3) Participating
      physicians often rely on external support systems for race-related issues, rather
      than support systems inside the organization; 4) Participating physicians
      perceive differences between their interpretations of potentially offensive race
      related work experiences and their non-minority colleagues' interpretations of
      the same experiences; and 5) Participating physicians are uncomfortable voicing
      race-related concerns at work. CONCLUSIONS: Creating a healthcare work
      environment that successfully supports diversity is as important as recruiting
      diversity across the workforce. Developing constructive ways to discuss race and
      race relations among colleagues in the workplace is a key step towards creating a
      supportive environment for employees and patients from all backgrounds.

PMID- 18618192
TI  - Why physicians favor use of percutaneous coronary intervention to medical
      therapy: a focus group study.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is performed in many
      patients with stable coronary artery disease, despite evidence of little clinical
      benefit over optimal medical therapy. OBJECTIVE: To examine physicians' beliefs,
      practices, and decision-making regarding elective PCI. DESIGN: Six focus groups,
      three with primary care physicians and three with cardiologists. Participants
      discussed PCI using hypothetical case scenarios. Transcripts were analyzed using
      grounded theory, and commonly expressed themes regarding the decision-making
      pathway to PCI were identified. PARTICIPANTS: Twenty-eight primary care
      physicians and 20 interventional and non-interventional cardiologists in Butte
      County, Orange County, and San Francisco Bay Area, California, in 2006. RESULTS:
      A number of factors led primary care physicians to evaluate non-symptomatic or
      minimally symptomatic patients for coronary artery disease and refer them to a
      cardiologist. The use of screening tests often led to additional testing and
      referral, as well as fear of missing a coronary stenosis, perceived patient
      expectations, and medicolegal concerns. The end result was a cascade such that
      any positive test would generally lead to the catheterization lab, where an
      "oculostenotic reflex" made PCI a virtual certainty. CONCLUSIONS: The widespread
      use of PCI in patients with stable coronary artery disease--despite evidence of
      little benefit in outcomes over medical therapy--may in part be due to
      psychological and emotional factors leading to a cascade effect wherein testing
      leads inevitably to PCI. Determining how to help physicians better incorporate
      evidence-based medicine into decision-making has important implications for
      patient outcomes and the optimal use of new technologies.

PMID- 18618191
TI  - Patient reported receipt of medication instructions for warfarin is associated
      with reduced risk of serious bleeding events.
AB  - BACKGROUND: Adverse drug events are an important cause of preventable
      hospitalizations. OBJECTIVE: To identify whether patient report of receipt of
      medication instructions and markers of complex care (multiple physicians, recent
      hospitalization) predict the risk of serious bleeding for older adults on
      warfarin. DESIGN: Prospective cohort study of older adults. PARTICIPANTS:
      Subjects filled new or refill prescriptions for warfarin at the time of
      enrollment. MEASUREMENTS: Hospitalizations were identified through a state-wide
      registry. Discharge summaries of hospitalizations for possible warfarin related
      bleeding events were reviewed by trained abstractors and clinical experts.
      Incidence rate ratios (IRR) were estimated based on person-months of exposure
      using Poisson regression models. RESULTS: From March 2002 through May 2003, we
      enrolled a total of 2346 adults on warfarin. Over a two-year follow-up period,
      there were 126 hospitalizations due to warfarin-related bleeding (4.6
      hospitalizations per 100 person-years of exposure). Patients who reported
      receiving medication instructions from either a physician or nurse plus a
      pharmacist had a 60% reduced rate of subsequently experiencing a serious bleeding
      event over the next 2 years (adjusted IRR 0.40, 95% CI 0.24-0.68). Having > or =
      4 physicians providing medication prescriptions over the last 3 months and
      filling prescriptions at > 1 pharmacy over the last 3 months were independently
      associated with increased bleeding rates (adjusted IRRs 2.37, 95% CI 1.22-4.57
      and 1.61, 95% CI 0.97-2.67, respectively). CONCLUSIONS: The rate of warfarin
      related hospitalization for bleeding is substantially lower for patients who
      report receiving medication instructions from a physician or nurse and a
      pharmacist.

PMID- 18618193
TI  - Large apical thrombus in a patient with persistent heart failure and
      hypereosinophilia: Loffler endocarditis.
AB  - Idiopathic hypereosinophilic syndrome is an uncommon leukoproliferative systemic
      disorder characterized by the overproduction of eosinophils and poor prognosis. A
      major source of morbidity and mortality of this syndrome is the associated
      cardiac involvement represented by endocardial thickening and mural thrombi. We
      report a 64-year-old woman with persistent symptoms of heart failure despite
      standard medical therapy. Echocardiography revealed reduced left ventricular
      filling due to a large apical mass; an abnormal diastolic filling pattern was
      also noticed. Complete blood count revealed remarkable hypereosinophilia. Cardiac
      magnetic resonance imaging demonstrated an apical thrombus and intense linear
      enhancement of the endocardium, which were compatible with Loffler endocarditis.
      Medical therapy, including corticosteroids and anticoagulation, was initiated
      promptly. The symptoms improved as the peripheral hypereosinophilia resolved in
      15 days. The patient was asymptomatic at the 1-year follow-up visit with complete
      regression of the apical thrombus and no evidence of restrictive cardiomyopathy.
      We report this case to draw attention to this particularly rare condition with
      poor prognosis since quick and accurate diagnosis and prompt initiation of
      therapy may improve symptoms and survival.

PMID- 18618194
TI  - Does the evidence make a difference in consumer behavior? Sales of supplements
      before and after publication of negative research results.
AB  - OBJECTIVE: To determine if the public consumption of herbs, vitamins, and
      supplements changes in light of emerging negative evidence. METHODS: We describe
      trends in annual US sales of five major supplements in temporal relationship with
      publication of research from three top US general medical journals published from
      2001 through early 2006 and the number of news citations associated with each
      publication using the Lexus-Nexis database. RESULTS: In four of five supplements
      (St. John's wort, echinacea, saw palmetto, and glucosamine), there was little or
      no change in sales trends after publication of research results. In one instance,
      however, dramatic changes in sales occurred following publication of data
      suggesting harm from high doses of vitamin E. CONCLUSION: Results reporting harm
      may have a greater impact on supplement consumption than those demonstrating lack
      of efficacy. In order for clinical trial evidence to influence public behavior,
      there needs to be a better understanding of the factors that influence the
      translation of evidence in the public.

PMID- 18618195
TI  - Physician burnout and patient-physician communication during primary care
      encounters.
AB  - BACKGROUND: Although previous studies suggest an association between provider
      burnout and suboptimal self-reported communication, no studies relate physician
      burnout to observed patient-physician communication behaviors. OBJECTIVE: To
      investigate the relationship between physician burnout and observed patient
      physician communication outcomes in patient-physician encounters. DESIGN:
      Longitudinal study of enrollment data from a trial of interventions to improve
      patient adherence to hypertension treatment. SETTING: Fifteen urban community
      based clinics in Baltimore, MD. PARTICIPANTS: Forty physicians and 235 of their
      adult hypertensive patients, with oversampling of ethnic minorities and poor
      persons. Fifty-three percent of physicians were women, and the average practice
      experience was 11.2 years. Among the 235 patients, 66% were women, 60% were
      African-American, and 90% were insured. MEASUREMENTS: Audiotape analysis of
      communication during outpatient encounters (one per patient) using the Roter
      Interaction Analysis System and patients' ratings of satisfaction with and trust
      and confidence in the physician. RESULTS: The median time between the physician
      burnout assessment and the patient encounter was 15.1 months (range 5.6-30).
      Multivariate analyses revealed no significant differences in physician
      communication based on physician burnout. However, compared with patients of low
      burnout physicians, patients of high-burnout physicians gave twice as many
      negative rapport-building statements (incident risk ratio 2.06, 95% CI 1.58-2.86,
      p < 0.001). Physician burnout was not significantly associated with physician or
      patient affect, patient-centeredness, verbal dominance, or length of the
      encounter. Physician burnout was also not significantly associated with patients'
      ratings of their satisfaction, confidence, or trust. CONCLUSIONS: Physician
      burnout was not associated with physician communication behaviors nor with most
      measures of patient-centered communication. However, patients engaged in more
      rapport-building behaviors. These findings suggest a complex relationship between
      physician burnout and patient-physician communication, which should be
      investigated and linked to patient outcomes in future research.

PMID- 18618196
TI  - Where should hospitalist programs be housed?

PMID- 18618197
TI  - The Demographic Assessment for Health Literacy (DAHL): a new tool for estimating
      associations between health literacy and outcomes in national surveys.
AB  - OBJECTIVE: To impute limited health literacy from commonly measured socio
      demographic data and to compare it to the Short-Test of Functional Health
      Literacy in Adults (S-TOFHLA) for estimating the influence of limited health
      literacy on health status in the elderly. METHODS: The Prudential Medicare Study
      assesses the S-TOFHLA score, leading to a "reference standard" classification of
      25% of people with inadequate literacy; the National Health Interview Survey has
      no such assessment. We estimated a regression of S-TOFHLA on sex, age, years of
      schooling, and race/ethnicity in The Prudential Medicare Study data to derive a
      Demographic Assessment for Health Literacy (DAHL) score, and imputed inadequate
      literacy to the 25% with the lowest DAHL scores. Using regression, we then
      examined associations between several health status measures (including
      hypertension, diabetes, physical and mental SF-12) and inadequate literacy
      (imputed or test-based). RESULTS: Estimates of association using imputed
      inadequate literacy closely approximate those obtained using S-TOFHLA-based
      inadequate literacy for most outcomes examined. CONCLUSIONS: As few population
      surveys measure health literacy, the DAHL, a readily calculated health literacy
      proxy score, may be useful for expanding the scope of health literacy research in
      national survey data.

PMID- 18618198
TI  - Anal cancer screening behaviors and intentions in men who have sex with men.
AB  - BACKGROUND: The incidence of anal cancer has increased in the past decade,
      especially among men who have sex with men (MSM) and HIV-infected individuals.
      There is controversy about whether to routinely screen for anal cancer in MSM.
      OBJECTIVES: To determine whether current anal cancer screening behaviors,
      intention, and concern differ by HIV serostatus and to identify characteristics
      of men who intend to seek anal cancer screening. DESIGN AND PARTICIPANTS: Cross
      sectional analysis of data collected from 901 HIV-infected and 1,016 HIV
      uninfected MSM from the Multicenter AIDS Cohort Study (MACS) in 2005-2006.
      MEASUREMENTS: Self-reported anal cancer screening history, attitudes, and
      intentions. RESULTS: A history of anal warts was relatively common in these men
      (39%), whereas having a recent anal Pap test (5%), intention to seek anal cancer
      screening in the next 6 months (12%), and concern about anal cancer (8.5%) were
      less common. Intention to seek anal cancer screening was associated with enabling
      factors (screening availability, health insurance), need factors (HIV-infection,
      history of anal warts), concern about anal cancer, and recent sexual risk taking.
      Among four large US cities, there was significant regional variability in anal
      cancer screening behaviors, intention, and concern (all p<0.001). Most MSM (76%)
      indicated they would go to their primary care physician for an anal health
      problem or question. CONCLUSIONS: This study demonstrates a low rate of anal
      cancer screening and intention to screen among MSM. As more evidence emerges
      regarding screening, primary care physicians should be prepared to discuss anal
      cancer screening with their patients.

PMID- 18618200
TI  - Identification of limited English proficient patients in clinical care.
AB  - BACKGROUND: Standardized means to identify patients likely to benefit from
      language assistance are needed. OBJECTIVE: To evaluate the accuracy of the U.S.
      Census English proficiency question (Census-LEP) in predicting patients' ability
      to communicate effectively in English. DESIGN: We investigated the sensitivity
      and specificity of the Census-LEP alone or in combination with a question on
      preferred language for medical care for predicting patient-reported ability to
      discuss symptoms and understand physician recommendations in English.
      PARTICIPANTS: Three hundred and two patients > 18 who spoke Spanish and/or
      English recruited from a cardiology clinic and an inpatient general medical
      surgical ward in 2004-2005. RESULTS: One hundred ninety-eight (66%) participants
      reported speaking English less than "very well" and 166 (55%) less than "well";
      157 (52%) preferred receiving their medical care in Spanish. Overall, 135 (45%)
      were able to discuss symptoms and 143 (48%) to understand physician
      recommendations in English. The Census-LEP with a high-threshold (less than "very
      well") had the highest sensitivity for predicting effective communication (100%
      Discuss; 98.7% Understand), but the lowest specificity (72.6% Discuss; 67.1%
      Understand). The composite measure of Census-LEP and preferred language for
      medical care provided a significant increase in specificity (91.9% Discuss; 83.9%
      Understand), with only a marginal decrease in sensitivity (99.4% Discuss; 96.7%
      Understand). CONCLUSIONS: Using the Census-LEP item with a high-threshold of less
      than "very well" as a screening question, followed by a language preference for
      medical care question, is recommended for inclusive and accurate identification
      of patients likely to benefit from language assistance.

PMID- 18618201
TI  - Substituted judgment: the limitations of autonomy in surrogate decision making.
AB  - Substituted judgment is often invoked as a guide for decision making when a
      patient lacks decision making capacity and has no advance directive. Using
      substituted judgment, doctors and family members try to make the decision that
      the patient would have made if he or she were able to make decisions. However,
      empirical evidence suggests that the moral basis for substituted judgment is
      unsound. In spite of this, many physicians and bioethicists continue to rely on
      the notion of substituted judgment. Given compelling evidence that the use of
      substituted judgment has insurmountable flaws, other approaches should be
      considered. One approach provides limits on decision making using a best interest
      standard based on community norms. A second approach uses narrative techniques
      and focuses on each patient's dignity and individuality rather than his or her
      autonomy.

PMID- 18618203
TI  - Contents of general practitioner-patient consultations in the treatment of
      depression.
AB  - BACKGROUND: Counseling of patients is an indispensable part of any drug treatment
      and even more so in the treatment of depression. OBJECTIVE: To describe the
      content of counseling additional to prescribing an antidepressant drug. SETTING:
      Sixty-three general practices from all over Germany. PATIENTS: Three hundred two
      patients with the diagnosis of either a depressive episode or a recurrent
      depressive disorder. MEASUREMENTS: Assessment of the content of the physician
      patient encounter by content analysis following the pivotal topic method. DESIGN:
      Qualitative study embedded in a drug utilization study on mirtazapine. RESULTS:
      In the initial sessions general practitioners focused on building a good
      therapeutic alliance, assessing the symptoms of illness, explaining the course of
      treatment, assuring medication compliance, and discussing problems of life. In
      the middle phase of treatment, physicians also dealt with building a therapeutic
      alliance, medication compliance, and the progress and course of illness. In the
      last phase relapse prevention was an important topic. Psychological topics were
      more important than medication topics. Almost no importance was given to
      management of side effects, change of cognitions, or suicidal tendencies.
      LIMITATIONS: No information is available on how content was actually discussed.
      Only encounters were observed where an antidepressant was prescribed.
      CONCLUSIONS: Counseling plays an important part in day-to-day encounters of
      general practitioners. Pharmacotherapy is embedded in comprehensive psychological
      care. Training programs for general practitioners should be specific in respect
      to different tasks and parts of the physician-patient encounter (e.g., building a
      therapeutic alliance, support for life problems or change of cognitions).

PMID- 18618204
TI  - Alcohol counseling reflects higher quality of primary care.
AB  - BACKGROUND: Some primary care physicians do not conduct alcohol screening because
      they assume their patients do not want to discuss alcohol use. OBJECTIVES: To
      assess whether (1) alcohol counseling can improve patient-perceived quality of
      primary care, and (2) higher quality of primary care is associated with
      subsequent decreased alcohol consumption. DESIGN: A prospective cohort study.
      SUBJECTS: Two hundred eighty-eight patients in an academic primary care practice
      who had unhealthy alcohol use. MEASUREMENTS: The primary outcome was quality of
      care received [measured with the communication, whole-person knowledge, and trust
      scales of the Primary Care Assessment Survey (PCAS)]. The secondary outcome was
      drinking risky amounts in the past 30 days (measured with the Timeline Followback
      method). RESULTS: Alcohol counseling was significantly associated with higher
      quality of primary care in the areas of communication (adjusted mean PCAS scale
      scores: 85 vs. 76) and whole-person knowledge (67 vs. 59). The quality of primary
      care was not associated with drinking risky amounts 6 months later. CONCLUSIONS:
      Although quality of primary care may not necessarily affect drinking, brief
      counseling for unhealthy alcohol use may enhance the quality of primary care.

PMID- 18618205
TI  - Age > or =50 does not influence outcome in laparoscopic gastric banding.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding is an accepted treatment for
      obesity. Age greater than 50 carries a theoretically increased risk from weight
      loss surgery and perhaps less clinical benefit in the long term. We compare
      results of gastric banding at age 50 and above with age below 50 in our unit.
      METHODS: Between April 2003 and November 2007, 1,335 patients, mean weight 121.7
      kg (range 73-268 kg), mean body mass index (BMI) 44.1 kg/m(2) (range 35-99),
      underwent gastric banding. Three hundred and twenty four patients had age > or
      =50. Band adjustments were usually carried out using fluoroscopy. RESULTS: There
      was no statistically significant difference in the preoperative weights and BMIs
      for the two patient groups (age < 50: weight 120.7 +/- 24.9, BMI 43.6 +/- 7.3
      kg/m(2); age > or = 50: weight 118 +/- 23.7 kg, BMI 43.8 +/- 7 kg/m(2)).
      Similarly, there was no statistically significant difference with regards to
      excess percent BMI loss in the two groups over 36 months (age < 50 = 49 +/- 27.9;
      age > or = 50 = 47.3 +/- 35.1). There was no difference in the incidence of
      complications with patient age. CONCLUSION: These results demonstrate that, at
      age > or =50, this procedure is successful in producing weight loss and, at the
      same time, has a complication rate comparable to younger patients.

PMID- 18618206
TI  - The impact of medicaid status on outcome after gastric bypass.
AB  - BACKGROUND: Socioeconomic status has been a predictor of poor outcome in many
      surgical diseases including morbid obesity. Potential differences in treatment
      and initial severity of disease have often not been well controlled in patients
      with bariatric surgery. This study was performed to compare the results of
      bariatric procedures in financially disadvantaged Medicaid patients compared to
      patients with Medicare and those with Commercial insurance under controlled
      conditions. METHODS: Prospectively collected data from 183 Medicaid, 77 Medicare
      and 570 Commercial/self-pay insurances were compared to determine the influence
      of poor economic status on outcome. All the patients received surgical care by
      the same surgeon at a large University-affiliated private hospital. RESULTS:
      Medicaid patients were larger (BMI 58.4 vs. 52.8 and 50.9, respectively) and had
      a greater incidence of serious comorbid conditions at outset. The death rate and
      complications were also significantly higher postoperatively in Medicaid
      patients. However, when the patients were matched for age and BMI, results became
      similar. CONCLUSION: Increases in postoperative mortality and morbidity appear to
      be associated with advanced disease because of poor access to care. When matched
      for age, BMI, and severity of disease, outcomes are similar. Changes in Medicaid
      policies could improve access and outcome.

PMID- 18618207
TI  - A comparison of noninvasive blood pressure measurement on the wrist with invasive
      arterial blood pressure monitoring in patients undergoing bariatric surgery.
AB  - BACKGROUND: In morbidly obese patients, oscillometric blood pressure measurements
      with an upper-arm cuff are often difficult to perform. The alternative method,
      invasive blood pressure monitoring, can be difficult to place and is associated
      with risks. A wrist-mounted blood pressure-monitoring device, the Vasotrac,
      provides accurate blood pressure measurements in lean patients. Even in the
      obese, wrist morphology remains relatively unchanged. We thus assessed the degree
      to which blood pressure measurements with the Vasotrac on the wrist and cuff
      measurements agree with invasive arterial blood pressure monitoring. METHODS: We
      evaluated 22 morbidly obese patients undergoing bariatric surgery lasting 3.8+/
      1.1 h. Intraoperative blood pressure was simultaneously measured using the
      Vasotrac mounted on one wrist; an arterial catheter was inserted in the opposite
      radial artery, and an oscillometric cuff was positioned on the upper arm.
      Preoperative patient comfort was evaluated on a scale from 1 to 10, with 10 being
      most uncomfortable, just after the first oscillometric cuff inflation. Values
      from the Vasotrac and arterial catheter were recorded at 5-s intervals. Bias,
      precision, and clinically acceptable agreement were calculated between the two
      continuous monitoring devices and between the arterial catheter and the cuff
      measurements, with the arterial catheter providing the reference value. RESULTS:
      The patients' age was 44.3+/-9.5 years (mean+/-SD), body mass index was 66.7+/
      13.8 kg/m2, and arm circumference was 48.6+/-7.5 cm. Patients found the Vasotrac
      more comfortable than the oscillometric device [1.7+/-1.8 vs 5.3+/-0.5
      (P=0.009)]. A total of 40,411 pairs of values from the Vasotrac and arterial
      catheter were recorded. Lin's concordance correlation coefficient (95% CI) for
      mean arterial blood pressure measured between the arterial line and the Vasotrac
      was 0.74 (0.67, 0.82). The bias (mean error) was -0.25 mmHg; however, the Bland
      Altman limits where 95% of individual pressure differences are expected to fall
      was (-20, 20) mmHg. The precisions for diastolic and systolic pressures were even
      worse. CONCLUSION: The Vasotrac was more comfortable than an oscillometric
      device. Although the average accuracy was good, individual mean Vasotrac and
      noninvasive blood pressure pressures often differed considerably from arterial
      values. These results suggest that the Vasotrac monitor should not be substituted
      for an arterial catheter in super-obese patients.

PMID- 18618208
TI  - Cardiac arrest after intragastric balloon insertion in a super-obese patient.
AB  - A super-obese patient who suffered from severe sleep apnea (SSA) and other
      comorbidities underwent insertion of a BioEnterics intragastric balloon (BIB)
      before bariatric surgery. During the night, he was victim of cardiac arrest.
      After cardiopulmonary resuscitation and return of spontaneous circulation, he was
      transferred to intensive care unit. Two hours later, he developed an unexpected
      symptomatic bradycardia, and BIB was removed. The patient had no further cardiac
      complications, but he had a poor neurological outcome. In our opinion, such a
      severe cardiac event was the result of several causes. The BIB induces vagal
      nerve activation by stretching the gastric wall. In addition, super-obese
      patients with sleep apnea and other comorbitities have an increased risk of
      potentially fatal cardiac arrhythmias especially during the night. For all these
      reasons, we think that these patients may benefit from further preoperative
      cardiac investigations and a more intensive control during the first
      postinsertion day.

PMID- 18618210
TI  - Relation between carbohydrate intake and weight loss after bariatric surgery.
AB  - BACKGROUND: Weight loss and long-term weight maintenance in bariatric surgery
      patients are related to maintaining satiety. It can be related to glycemic load
      (GL) and carbohydrate (g CHO) intake. The aim of this study was to investigate
      the effect of g CHO and GL and in weight loss on patients who had undergone
      bariatric surgery. METHOD: The following measurements/calculations were conducted
      as follows: current body weight (kg), current BMI, percentage of excess weight
      loss (PEWL), average monthly weight loss (AMWL), energy intake (kcal per day),
      and GL calculation. Correlations were found among the studied variables. A
      multiple linear regression analysis of diet variables executed with GL and weight
      loss. RESULTS: The population presented 66% of EWL. The average of total energy
      intake (TEI) was 1220+/-480, and the calculated GL resulted in an average of
      73.2. Negative correlations were found between AMWL and TEI (p=0.04), and between
      AMWL and GL (p=0.009); furthermore, a negative correlation was found between
      carbohydrate intake in grams and AMWL (p=0.003). A positive correlation (p=0.017)
      was found between GL and TEI. Weight loss and GL were also correlated. Among the
      intake variables, GL and g CHO consumed are held accountable for 62 percent of
      AMWL. The multiple linear regression analysis showed that GL and carbohydrate
      grams (g CHO) account for 62% of AMWL. CONCLUSION: The glycemic load and grams of
      carbohydrate are intake factors that can be useful tools in weight loss and long
      term weight maintenance on patients who have undergone Roux-en-Y Gastric Bypass
      (RYGB).

PMID- 18618212
TI  - Musculoskeletal trauma services in Mozambique and Sri Lanka.
AB  - There is currently an escalating epidemic of trauma-related injuries due to road
      traffic accidents and armed conflicts. This trauma occurs predominantly in rural
      areas where most of the population lives. Major ways to combat this epidemic
      include prevention programs, improved healthcare facilities, and training of
      competent providers. Mozambique and Sri Lanka have many common features including
      size, economic system, and healthcare structure but have significant differences
      in their medical education systems. With six medical schools, Sri Lanka graduates
      1000 new physicians per year while Mozambique graduates less than 50 from their
      singular school. To supplement the low number of physicians, a training course
      for surgical technicians has been implemented. Examination of district hospital
      staffing and the medical education in these two countries might provide for
      improving trauma care competence in other developing countries. Musculoskeletal
      education is underrepresented in most medical school curricula around the world.
      District hospitals in developing countries are commonly staffed by recently
      graduated general medical officers, whose last formal education was in medical
      school. There is an opportunity to improve the quality of trauma care at the
      district hospital level by addressing the musculoskeletal curriculum content in
      medical schools.

PMID- 18618213
TI  - Navigation did not improve the precision of minimally invasive knee arthroplasty.
AB  - Potential advantages of minimally invasive total knee arthroplasty (TKA) include
      decreased pain, faster recovery, and increased quadriceps muscle strength.
      Computer-assisted navigation has been associated with more accurate component
      alignment. We evaluated two groups of 50 patients who had minimally invasive TKAs
      performed with and without navigation by two surgeons. A comparison of 50
      previous TKAs by each of the two surgeons showed similar results. The mean
      operative times for the navigation and nonnavigation groups were 112 minutes
      (range, 63-297 minutes) and 54 minutes (range, 35-86 minutes), respectively. The
      mean estimated blood losses, mean Knee Society pain as well as functional scores
      and mean component alignments were similar. The number of knees that deviated by
      more than 3 degrees from the normal anatomic axis was three and one in the
      navigated and nonnavigated groups, respectively. Complication rates were 6% and
      4% in the navigated and nonnavigated groups, respectively. Our data demonstrate
      no distinct advantage of navigation when combined with a minimally invasive
      approach. LEVEL OF EVIDENCE: Level II, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18618214
TI  - Myasthenia gravis and the thymus gland. A historical review.
AB  - The first report of an association between myasthenia gravis (MG) and the thymus
      gland was in 1901. Although the underlying mechanisms are uncertain, thymic
      abnormalities are clearly associated with MG. This review article summarises,
      from a historical point of view, our knowledge of these associations, and the
      surgical and medical treatment of MG, including symptom management,
      immunosuppression, intravenous immunoglobulin and plasmapheresis.

PMID- 18618215
TI  - Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a
      positive association with combined CYP/GST genotypes.
AB  - The cytochrome P450 family (CYPs) and the glutathione S-transferase (GSTs)
      enzymes play an important role in the metabolism of environmental carcinogens and
      of oestrogen and can affect breast cancer risk. In this study we examine the role
      of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk
      in Brazilian women. The study population consisted of 102 incident breast cancer
      cases and 102 healthy controls. Genotyping analyses were performed by PCR-based
      methods. A significant finding was observed between GSTP1 Ile-Val polymorphism
      and breast cancer risk (OR = 1.81; CI 95% = 1.04-3.16). A significant association
      was observed between women with 0-2 risk genotypes and those with 4 or more risk
      genotypes (OR = 2.42; CI 95% = 1.13-5.18) when the potential combined effects of
      the risk genotypes were examined. No significant differences between cases and
      controls were found correlating the genotypes and the clinical-histopathological
      parameters. In conclusion, in our population only GSTP1 was associated with
      breast cancer risk. However, when the genes were tested in combination, a
      significant association in the breast cancer risk was observed.

PMID- 18618216
TI  - Association of ECRG2 TCA short tandem repeat polymorphism with the risk of
      oesophageal cancer in a North Indian population.
AB  - Oesophageal cancer-related gene (ECRG2) is a tumour suppressor gene and it has
      been suggested that a triplet TCA short tandem repeat (STR) in the noncoding
      region of exon 4 plays a role in genetic susceptibility to oesophageal cancer. In
      the present study, ECRG2 STR polymorphism was studied in 134 patients with
      oesophageal cancer and 194 controls, using PCR and polyacrylamide gel
      electrophoresis. The results showed a higher frequency of the ECRG2 TCA (3)/TCA
      (4) genotype in cancer patients than in controls (odds ratio 2.6, 95% CI 1.0-6.4,
      p = 0.03). The association of the ECRG2 TCA (3)/TCA (4) genotype with clinical
      characteristics showed an increased risk for squamous cell histology (2.8, 95% CI
      1.1-7.1, p = 0.03), while no association with tumor location or lymph node
      involvement was observed. Interaction of tobacco, alcohol and occupational
      exposure with the ECRG2 genotypes did not show modulation of risk. In conclusion,
      the ECRG2 TCA (3)/TCA (4) genotype is associated with the risk of oesophageal
      carcinoma in a North Indian population.

PMID- 18618217
TI  - DNA damage in lymphocytes and buccal mucosa cells of children with malignant
      tumours undergoing chemotherapy.
AB  - The aim of the present study was to evaluate DNA damage (micronucleus) in
      cytokinesis-blocked lymphocytes and exfoliated buccal mucosa cells from children
      with malignant tumours and under chemotherapy. Micronucleated cells (MNCs) were
      assessed from children before and during chemotherapy. A total of 21 healthy
      children (controls), matched for gender and age, were used as control. The
      results pointed out higher frequencies of micronucleated lymphocytes in children
      with malignant tumour before any therapy when compared to healthy probands.
      Furthermore an increase of micronucleated lymphocytes during chemotherapy was
      detected when compared to the data obtained before chemotherapy. No statistically
      significant increases of MNCs were noticed in buccal mucosa cells at any of the
      timepoints evaluated. Taken together, these data indicate that the presence of
      malignant tumours may increase the frequency of DNA damage in circulating
      lymphocytes, these cells being more sensitive for detecting chromosome
      aberrations caused by anti-cancer drugs.

PMID- 18618218
TI  - Comparison of free plasma metanephrines enzyme immunoassay with (131)I-MIBG scan
      in diagnosis of pheochromocytoma.
AB  - Measurement of free plasma metanephrines (metanephrine and normetanephrine),
      usually performed by high-performance liquid chromatography with electrochemical
      detection (HPLC-ECD), has been recommended as the single biochemical test of
      choice for the diagnosis of pheochromocytoma. Alternatively, a widely available,
      simple means to measure these biomarkers with enzyme immunoassay (EIA) needs to
      be studied. The aim of this study was to investigate the diagnostic efficacy of
      such a method in comparison with (131)I-metaiodobenzylguanidine (MIBG) whole body
      scan (WBS) in patients with pheochromocytoma. We enrolled patients undergoing
      (131)I-MIBG WBS due to clinical findings suggestive of pheochromocytoma (n = 45),
      and patients with primary hypertension (n = 36). All subjects had blood tests for
      free plasma metanephrine (MN) and normetanephrine (NM) with a commercially
      available EIA kit. WBS was positive in 30 pheochromocytoma patients and negative
      in 15 refuted ones, with 100% accuracy. The sensitivity, specificity and accuracy
      of MN and NM in combination (either or both positive) were 96.7%, 86.3% and
      90.1%, showing comparable diagnostic performance both to (131)I-MIBG WBS (all p >
      0.1), and also to the same markers measured with HPLC-ECD reported in the
      literature. These results showed that the EIA method may be eligible as an
      alternative to HPLC-ECD for plasma metanephrine determination in the
      identification of pheochromocytoma.

PMID- 18618219
TI  - Fulminant type 1 diabetes mellitus observed in insulin receptor substrate 2
      deficient mice.
AB  - The objective of this study was to characterise the fulminant type 1 diabetes
      mellitus (DM) accompanying abrupt hyperglycaemia and ketonuria observed in
      insulin receptor substrate 2 (IRS2)-deficient mice. IRS2-deficient mice
      backcrossed onto the original C57BL/6J:Jc1 background (B6J-IRS2(-/-) mice) for
      more than 10 generations were used. Eight male IRS2-deficient mice with ketonuria
      and abrupt increase in plasma glucose concentrations over 25 mmol/l were used as
      the fulminant type 1 diabetic mice (diabetic mice) and 8 male IRS2-deficient mice
      (8 weeks old) without glycosuria were used as the control mice. Plasma
      metabolite, immunoreactive insulin (IRI) and C-peptide concentrations, hepatic
      energy metabolism related enzyme activities and histopathological change in
      pancreatic islets were investigated. The diabetic mice showed significantly
      higher plasma glucose and cholesterol concentrations and lower plasma IRI and C
      peptide concentrations than the control mice. In livers of the diabetic mice,
      glycolytic and malate-aspartate shuttle enzyme activities decreased significantly
      and gluconeogenic, lipogenic and ketone body synthesis enzyme activities
      increased significantly compared to those in the control mice. The pancreatic
      islets of the diabetic mice decreased significantly in size and number of beta
      cells. The diabetic IRS2-deficient mice did not show the islet-related antibodies
      observed in the diabetic NOD mice in their sera. The characteristics of the
      diabetic IRS2-deficient mice resembled those of the human nonautoimmune fulminant
      type 1 DM. IRS2-deficient mice may be a useful animal model for studying the
      degradation mechanism of pancreatic beta cells in the process of development of
      fulminant type 1 DM.

PMID- 18618220
TI  - Oxidative stress and protein glycation in primary hypothyroidism. Male/female
      difference.
AB  - Oxidative stress (OS) has recently been documented in hypothyroidism, a disease
      more prevalent in women. In general, OS is reported to be more prevalent in
      males. However, the effect of gender on OS and protein glycation in
      hypothyroidism has not been addressed. Blood samples from 37 recently diagnosed
      primary hypothyroid patients were collected before initiation of thyroxine
      therapy. Serum glucose, thyroid and lipid profiles were estimated. Glutathione
      (GSH), malondialdehyde (MDA), protein carbonylation (PCO) and fructosamine levels
      were analysed. GSH was found to be lower, whereas MDA, fructosamine and PCO
      levels were higher in male than in female patients. Level of MDA was
      significantly correlated with fructosamine, protein carbonyls, cholesterol, low
      density and high-density lipoprotein cholesterol, triglyceride and GSH in
      hypothyroid patients. We found OS to be more prevalent in male hypothyroid
      patients. The positive association of MDA with fructosamine indicates that
      enhanced lipid peroxidation could be a plausible contributor for accelerated
      glycation of protein. Considering the negative influence of OS on health, extra
      attention should be paid to male hypothyroid patients in spite of the low
      prevalence of this disease in them.

PMID- 18618221
TI  - Does simultaneous determination of LDL and HDL particle size improve prediction
      of coronary artery disease risk?
AB  - BACKGROUND: Alterations in plasma lipoprotein subclass distribution affect the
      risk for coronary artery disease (CAD). However, it is unclear whether the
      determination of low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
      phenotypes may or may not improve the ability to predict CAD development.
      METHODS: Polyacrylamide gradient (3-31%) gel electrophoresis was used to
      simultaneously determine size and distribution of lipoprotein subclasses in 181
      CAD patients and 178 controls. RESULTS: Mean LDL and HDL subclass sizes were
      significantly smaller in patients than in controls (p < 0.001). Multivariate
      logistic regression analysis showed that small dense LDL particles were
      independent CAD risk predictors (OR = 2.867, p < 0.01), even when adjusted for
      other traditional risk factors, while small HDL particles lost their significance
      after adjustment (OR = 2.071, p = 0.054). The area under the ROC curve for LDL
      (0.671) and HDL (0.643) particle size measurement demonstrated low clinical
      accuracy when compared to the combination of traditional lipid risk factor
      measurements. CONCLUSIONS: CAD is associated with the predominance of smaller LDL
      and HDL particles. However, simultaneous determination of these two lipoprotein
      phenotypes provides no additional power in discriminating CAD and non-CAD
      subjects, beyond that obtained by the traditional risk factors.

PMID- 18618222
TI  - Rapid access to information resources in clinical biochemistry: medical
      applications of Personal Digital Assistants (PDA).
AB  - Laboratory specialists currently need to access scientific-based information at
      anytime and anywhere. A considerable period of time and too much effort are
      required to access this information through existing accumulated data. Personal
      digital assistants (PDA) are supposed to provide an effective solution with
      commercial software for this problem. In this study, 11 commercial software
      products (UpToDate, ePocrates, Inforetrive, Pepid, eMedicine, FIRST Consult, and
      5 laboratory e-books released by Skyscape and/or Isilo) were selected and the
      benefits of their use were evaluated by seven laboratory specialists. The
      assessment of the software was performed based on the number of the tests
      included, the software content of detailed information for each test-like
      process, method, interpretation of results, reference ranges, critical values,
      interferences, equations, pathophysiology, supplementary technical details such
      as sample collection principles, and additional information such as linked
      references, evidence-based data, test cost, etc. In terms of technique, the
      following items are considered: the amount of memory required to run the
      software, the graphical user interface, which is a user-friendly instrument, and
      the frequency of new and/or up-date releases. There is still no perfect program,
      as we have anticipated. Interpretation of laboratory results may require software
      with an integrated program. However, methodological data are mostly not included
      in the software evaluated. It seems that these shortcomings will be fixed in the
      near future, and PDAs and relevant medical applications will also become
      indispensable for all physicians including laboratory specialists in the field of
      training/education and in patient care.

PMID- 18618223
TI  - Increased levels of lipoprotein(a) in non-smoking aortic dissection patients.
AB  - OBJECTIVES: To investigate lipoprotein(a) (Lp(a)) serum levels in patients with
      aortic dissection and the influence of smoking on the level of Lp(a) in aortic
      dissection patients. METHODS: An age-and sex-matched case-control study was
      conducted. Lp(a) levels in patients with aortic dissection (n = 52) and healthy
      subjects (n = 104) were studied. The strength of associations between Lp(a) serum
      levels and aortic dissection was assessed by means of multivariate logistic
      regression analysis. RESULTS: Patients with aortic dissection had significantly
      higher Lp(a) serum levels (median, 17.6 mg/dl; range, 6.4-88.7 mg/dl) compared to
      healthy individuals (median, 12.4 mg/dl; range, 4.9-26.4 mg/dl) (p = 0.005). The
      Lp(a) concentration in non-smoking patients with aortic dissection (median, 19.1
      mg/dl, range, 10.5-88.7 mg/dl) significantly surpassed that of the smoking
      patients with aortic dissection of comparable age (median, 10.7 mg/dl; range, 6.4
      22.1 mg/dl) (p < 0.0001). Multivariate analysis confirmed an independent
      association between Lp(a) and aortic dissection in the non-smoking population (p
      = 0.001). CONCLUSIONS: Serum Lp(a) level is significantly elevated in non-smoking
      patients with aortic dissection independently of other cardiovascular risk
      factors. Therefore, determination of Lp(a) levels may be important in identifying
      subjects at risk of aortic dissection among nonsmokers.

PMID- 18618224
TI  - Plasma Epstein-Barr viral load predicting response after chemotherapy for post
      transplant lymphoproliferative disease.
AB  - Transplant patients are particularly at risk of developing B post-transplant
      lymphoproliferative disease (PTLD) related to intensive immunosuppressive
      treatment to prevent graft rejection. In EBV-positive PTLDs, EBV-DNA can be found
      in the patients' peripheral blood. Several methods have been described to assess
      peripheral blood EBV viral load. We report a case of a 13-year-old child who
      developed EBV-positive PTLD after renal transplantation. We assessed EBV plasma
      viral load by quantitative PCR and we found that the clearance of EBV-DNA
      correlated well with response to treatment.

PMID- 18618225
TI  - Paraneoplastic opsoclonus-myoclonus ataxia associated with non-small-cell lung
      carcinoma.
AB  - We report a case of the paraneoplastic opsoclonus-myoclonus ataxia syndrome in a
      patient with non-small cell lung carcinoma, which represents a highly unusual
      association. The patient simultaneously manifested both severe neurologic
      symptoms and widely metastatic disease, complicating her treatment.

PMID- 18618226
TI  - Genomic changes in progression of low-grade gliomas.
AB  - Using a one-megabase BAC-based array comparative genomic hybridization technique
      (aCGH), we have investigated a series of 16 low-grade gliomas (LGGs) and their
      subsequent progression to higher-grade malignancies. The most frequent chromosome
      imbalances in primary tumors were gains of chromosomes 7q, 8q, and 22q, and
      losses of chromosomes 1p, 13q, and 19q. In tumor progression, gains of
      chromosomes 11q, 7q, 20q, and 21q, and losses of chromosomes 9p, including CDKN2A
      locus, 19q, 14q, 1p, and 6q were the most frequent genomic disequilibria.
      Progressive tumors were more imbalanced than primary tumors in terms of altered
      chromosomal arms (3.8 vs. 6.6 in mean abnormal chromosomal arm) and altered BACs
      (17 vs. 21%). Interestingly, putative novel candidate genes associated with
      glioma progression were identified, in particular DOCK8, PTPRD, CER1, TPHO, DHFR,
      MSH3, ETS1, ACACA, and CSE1L.

PMID- 18618227
TI  - Eosinophilia and first-line coagulation testing.
AB  - Although eosinophilia (eosinophil count >0.60 x 10(9)/l), is a prothrombotic
      condition, little is known on the association between eosinophil count in blood
      and first-line coagulations tests, including fibrinogen, activated partial
      thromboplastin time (APTT), prothrombin time (PT) and platelet count. Cumulative
      results of APTT, PT, fibrinogen, platelet and eosinophil counts were retrieved
      from 6,944 outpatients >15 years old referred to our laboratory for routine blood
      testing over the previous 3 years. The median value and the percentage of
      patients with abnormal values of platelet count and fibrinogen but not APTT and
      PT, were significantly higher in patients with eosinophilia. This epidemiological
      association in a large subset of patients provides an additional potential
      mechanism to explain the link between eosinophilia and thrombosis and is
      consistent with the hypothesis that platelet count and fibrinogen might be
      worthwhile assessing in the presence of an abnormal eosinophil count.

PMID- 18618228
TI  - MTHFR C677TT, PAI1 4G-4G, V Leiden Q506, and prothrombin G20210A in
      hepatocellular carcinoma with and without portal vein thrombosis.
AB  - We studied thrombophilic genetic factors (TGFs) MTHFR C677TT, PAI1 4G-4G, V
      Leiden Q506, prothrombin G20210A as risk factors in 94 patients with HCC with and
      without portal vein thrombosis (PVT), compared with 214 patients with liver
      cirrhosis (LC) with and without PVT and 94 healthy controls (HC). The OR (95% CI)
      for MTHFR C677TT with HCC was 3.85 (1.55-7.39) vs. HC. The OR for PAI1 4G-4G in
      HCC, was 2.87 (1.27-6.55) vs. HC. Also prothrombin G20210A was significantly more
      frequent among HCC, mainly in patients with PVT, while V Leiden factor was
      equally distributed among HCC and HC. Differences were more significant in
      patients with associated PVT. These findings suggest that frequently TGFs are
      needed for patients to be at risk of HCC and PVT. We conclude that in all
      patients with chronic liver disease TGF screening should be performed to
      individuate patients at risk of HCC and PVT.

PMID- 18618229
TI  - Tyrosine hydroxylase expression and Cdk5 kinase activity in ataxic cerebellum.
AB  - Ataxia has been associated with abnormalities in neuronal differentiation and
      migration, which are regulated by Cyclin-dependent kinase 5 (Cdk5). The
      cerebellum of mice lacking Cdk5 or its activator, p35, resembles those of ataxic
      reeler and scrambler mice, suggesting that Cdk5 may contribute to ataxic
      pathology. As with other ataxic mice, the pogo/pogo mouse shows aberrant
      cerebellar tyrosine hydroxylase (TH) expression. Since Cdk5 phosphorylates and
      upregulates TH expression, we sought to analyze (i) Cdk5 activity in the pogo
      cerebellum, which exhibits abnormal TH expression, and (ii) TH expression in the
      cerebellum of p35-/- and p39-/- mice, which display reduced Cdk5 activity.
      Interestingly, we found that increased TH expression in the pogo cerebellum
      coincided with reduced Cdk5 activity. However, reduced Cdk5 activity in both p35
      /- and p39-/- cerebellum did not correspond to defects in TH expression.
      Together, these suggest that abnormal TH expression in the cerebellum might be
      regulated by mechanisms other than Cdk5 activity.

PMID- 18618230
TI  - Surface modification of pharmaceutical nanocarriers with ascorbate residues
      improves their tumor-cell association and killing and the cytotoxic action of
      encapsulated paclitaxel in vitro.
AB  - PURPOSE: To evaluate the potential of ascorbate as a novel ligand in the
      preparation of pharmaceutical nanocarriers with enhanced tumor-cell specific
      binding and cytotoxicity. METHODS: Palmitoyl ascorbate was incorporated into
      liposomes at varying concentrations. A stable formulation was selected based on
      size and zeta potential measurements. A co-culture of cancer cells with GFP
      expressing non-cancer cells was used to determine the specificity of palmitoyl
      ascorbate liposome binding. Liposomes were fluorescently labeled to facilitate
      analysis by flow cytometry and fluorescence microscopy. The cytotoxic action of
      palmitoyl ascorbate liposomes against a variety of cell types was assayed using a
      standard metabolic assay. The cytotoxic effect of a low dose of paclitaxel
      incorporated in palmitoyl ascorbate liposomes on various cell lines was also
      determined. RESULTS: Palmitoyl ascorbate liposomes associated preferentially with
      various cancer cells compared to non-cancer cells in a co-culture model.
      Palmitoyl ascorbate liposomes exhibited anti-cancer toxicity in numerous cancer
      cell lines. Furthermore, ascorbate liposomes enhanced the effectiveness of
      encapsulated paclitaxel compared to paclitaxel encapsulated in 'plain' liposomes.
      CONCLUSIONS: Surface modification of liposomes with ascorbate residues represents
      a novel way to target and kill certain types of tumor cells and additionally can
      potentiate the effect of paclitaxel delivered by the liposomes.

PMID- 18618231
TI  - Prepregnancy obesity prevalence in the United States, 2004-2005.
AB  - OBJECTIVE: To provide a current estimate of the prevalence of prepregnancy
      obesity in the United States. METHODS: We analyzed 2004-2005 data from 26 states
      and New York City (n = 75,403 women) participating in the Pregnancy Risk
      Assessment Monitoring System, an ongoing, population-based surveillance system
      that collects information on maternal behaviors associated with pregnancy.
      Information was obtained from questionnaires self-administered after delivery or
      from linked birth certificates; prepregnancy body mass index was based on self
      reported weight and height. Data were weighted to provide representative
      estimates of all women delivering a live birth in each particular state. RESULTS:
      In this study, about one in five women who delivered were obese; in some state,
      race/ethnicity, and Medicaid status subgroups, the prevalence was as high as one
      third. State-specific prevalence varied widely and ranged from 13.9 to 25.1%.
      Black women had an obesity prevalence about 70% higher than white and Hispanic
      women (black: 29.1%; white: 17.4%; Hispanic: 17.4%); however, these race-specific
      rates varied notably by location. Obesity prevalence was 50% higher among women
      whose delivery was paid for by Medicaid than by other means (e.g., private
      insurance, cash, HMO). CONCLUSION: This prevalence makes maternal obesity and its
      resulting maternal morbidities (e.g., gestational diabetes mellitus) a common
      risk factor for a complicated pregnancy.

PMID- 18618232
TI  - An investigation of paternity status and other factors associated with racial and
      ethnic disparities in birth outcomes in Milwaukee, Wisconsin.
AB  - OBJECTIVE: To examine factors associated with preterm birth and low birthweight
      and the role of paternity status in birth outcomes among racial/ethnic groups in
      Milwaukee. METHODS: Retrospective analysis of data on 151,869 singleton live
      births (1993-2006) from the City of Milwaukee, Wisconsin. Multivariate logistic
      regression models were used to examine demographic and medical factors associated
      with racial/ethnic disparities in preterm birth and low birthweight. RESULTS:
      African-Americans, whites, Hispanics, and women of "other" racial groups
      accounted for 46%, 33%, 16%, and 5% of births, respectively. Preterm birth and
      low birthweight rates were three times greater for African-American women
      compared to whites. Compared to white women, the odds of preterm birth were 82%
      and 35% greater for African-American and other minority women, respectively. All
      minority women had greater adjusted odds of low birthweight than whites, with
      African-American women at greatest risk (OR 2.36:2.23-2.49). Across racial/ethnic
      groups, significant predictors of both outcomes included being unmarried with no
      child's father on record, maternal smoking, chronic hypertension, previous
      preterm birth, and inadequate and adequate plus prenatal care. Paternity status
      had a gradient effect for whites and Hispanics with unmarried women with no
      child's father's name on record at greatest risk, followed by those with court
      established paternity and those with paternity statement at lowest risk for both
      outcomes. CONCLUSIONS: Implementing policies/programs that promote smoking
      cessation, proper management of maternal conditions, targeted interventions for
      women with previous preterm birth, and paternal involvement have the potential to
      reduce disparities in birth outcomes.

PMID- 18618233
TI  - Informal and formal long-term care for frail older adults in Cairo, Egypt: family
      caregiving decisions in a context of social change.
AB  - This paper explores the factors that lead family caregivers to place their frail
      older relatives into long-term care centers in Cairo, Egypt despite norms of
      family care. Semi-structured interviews were conducted with 18 "case" caregivers
      who placed their older relatives into long-term care and 17 "control" caregivers
      who provided for their older relatives at home. Cases and controls differed in
      their relationship to the older adult, number and proximity of supportive
      siblings, and perceived health status of the older adult. Caregivers who used
      long-term care justified their decision by stressing the need for relief from the
      burden of caregiving, and by conceiving long-term care as part of a broadened
      definition of family care. Egyptians are devising new strategies of care despite
      persistent norms of reciprocity among kin. As demographic, epidemiologic, and
      socioeconomic changes continue, families may adopt new combinations of care to
      support their frail older relatives. Findings underscore the need for population
      based research about strategies of caring for frail older relatives in this
      context.

PMID- 18618234
TI  - Increased bradykinesia in Parkinson's disease with increased movement complexity:
      elbow flexion-extension movements.
AB  - The present research investigates factors contributing to bradykinesia in the
      control of simple and complex voluntary limb movement in Parkinson's disease (PD)
      patients. The functional scheme of the basal ganglia (BG)-thalamocortical circuit
      was described by a mathematical model based on the mean firing rates of BG
      nuclei. PD was simulated as a reduction in dopamine levels, and a loss of
      functional segregation between two competing motor modules. In order to compare
      model simulations with performed movements, flexion and extension at the elbow
      joint is taken as a test case. Results indicated that loss of segregation
      contributed to bradykinesia due to interference between competing modules and a
      reduced ability to suppress unwanted movements. Additionally, excessive
      neurotransmitter depletion is predicted as a possible mechanism for the increased
      difficulty in performing complex movements. The simulation results showed that
      the model is in qualitative agreement with the results from movement experiments
      on PD patients and healthy subjects. Furthermore, based on changes in the firing
      rate of BG nuclei, the model demonstrated that the effective mechanism of Deep
      Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of
      STN, partial synaptic failure of efferent projections, or excitation of
      inhibitory afferent axons even though the underlying methods of action may be
      quite different for the different mechanisms.

PMID- 18618235
TI  - Identification of putative functional motifs in viral proteins essential for
      human cytomegalovirus DNA replication.
AB  - Six of the eleven genes essential for Human cytomegalovirus (HCMV) DNA synthesis
      have been analyzed for putative structural motifs that may have a significant
      functional role in DNA replication. The genes studied encode for the DNA
      polymerase accessory protein (UL44), single-stranded DNA binding protein (UL57),
      primase-helicase complex (UL70, UL102, and UL105), and the putative initiator
      protein (UL84). The full-length open reading frames of these genes were highly
      conserved between ten isolates with amino acid sequence identity of >97% for all
      genes. Using ScanProsite software from the Expert Protein Analysis System
      (ExPASy) proteomics server, we have mapped putative motifs throughout these HCMV
      replication genes. Interesting motifs identified include casein kinase-2 (CKII)
      phosphorylation sites, a microbodies signal motif in UL57, and an ATP binding
      site in the putative UL105 helicase. Our investigations have also elucidated
      motif-rich regions of the UL44 DNA polymerase accessory protein and identified
      cysteine motifs that have potential implications for UL57 and UL70 primase. Taken
      together, these findings provide insights to regions of these HCMV replication
      proteins that are important for post-translation modification, activation, and
      overall function, and this information can be utilized to target further research
      into these proteins and advance the development of novel antiviral agents that
      target these processes.

PMID- 18618236
TI  - Commonsense illness beliefs, adherence behaviors, and hypertension control among
      African Americans.
AB  - Hypertension, particularly among African Americans, has been increasing in
      importance in the past 10 years. One aspect of this problem is poor disease
      management. This study examined illness beliefs, behaviors, and hypertension
      control among 102 African American outpatients. Participants were interviewed
      about their commonsense beliefs concerning hypertension and its management in
      accordance with Leventhal's commonsense model of self-regulation (CSM). Also
      assessed were medication adherence, stress-reducing behaviors, and lifestyle
      behaviors recommended for blood pressure control. Blood pressure was measured at
      about the time of interviewing. Results indicated that endorsement of a medical
      belief model of hypertension (i.e., caused and controlled by factors such as
      diet, age, and weight) was cross-sectionally associated with lower systolic blood
      pressure, a relationship that was statistically mediated by lifestyle behaviors
      (e.g., cut down salt, exercise). Endorsement of a stress belief model (i.e.,
      stress is the main factor in hypertension cause and control) was associated with
      engagement in stress-related behaviors but not with blood pressure. These results
      further support the utility of the CSM for understanding patients' disease
      management behaviors.

PMID- 18618237
TI  - Gender differences in medication management capacity in HIV infection: the role
      of health literacy and numeracy.
AB  - Health literacy is emerging as a key element for successful medication management
      and empirical support for the efficacy of numeracy in the health context is
      rising as well. Little is known, however, about their unique effects among women
      and men. Given the importance of accurate medication management for effective
      treatment of HIV, the relation of these variables to medication management needs
      to be assessed. We therefore tested the relation of health literacy (reading
      comprehension) and numeracy to one's ability to manage a "mock" HIV regimen and
      whether men and women differed in these abilities. Results showed that women were
      less able than men to follow medication instructions and answer questions about
      the mock regimen. Numeracy mediated the relationship between gender and
      medication management. These findings highlight skills used in managing
      medication regimens and suggest avenues to target for identification and
      intervention in medication management among women and men with HIV.

PMID- 18618238
TI  - Habitual response to stress in recovering adolescent anorexic patients.
AB  - OBJECTIVE: Although previous research has investigated the stress response in
      acutely anorexic patients, there is currently little research addressing this
      response in recovering adolescent anorexic girls. Therefore, this study
      investigated partially and fully weight-restored anorexic adolescent girls'
      psychological and physiological response to a standardized stressor. METHODS: We
      measured the heart rate and affect of 17 adolescent recovering anorexic patients
      and 40 healthy age-matched controls during two conditions of the Stress Induced
      Speech Task (SIST): Free Association and Stress Task. Recovering patients were
      either partially or fully weight-restored. RESULTS: Compared to the controls, the
      recovering anorexic girls reported greater overall habitual psychological
      distress and higher levels of negative affect during the standardized stressor.
      However, recovering patients did not show a muted heart rate response during the
      stressor. Neither recovering anorexics nor controls demonstrated a correspondence
      between heart rate and positive or negative affect. DISCUSSION: Although the
      physiological stress response of recovering adolescent anorexic patients was
      similar to controls, the psychological response of partially and fully weight
      restored anorexic adolescents appears similar to that of acutely anorexic
      adolescents. Treatment implications are discussed in terms of the persistence of
      negative affect and treatment resistance.

PMID- 18618239
TI  - Expression of TNF-alpha leader sequence renders MCF-7 tumor cells resistant to
      the cytotoxicity of soluble TNF-alpha.
AB  - Transmembrane TNF-alpha (tmTNF-alpha) contains a leader sequence (LS) that can be
      phosphorylated and cleaved at its cytoplasmic portion, inducing IL-12 production.
      We observed that the breast cancer cell line MDA-MB-231 expressing transmembrane
      TNF-alpha (tmTNF-alpha) at high level was resistant to soluble TNF-alpha (sTNF
      alpha)-induced cytotoxicity, accompanied by constitutive NF-kappaB activation. In
      contrast, MCF-7 cells expressing tmTNF-alpha at very low level were sensitive to
      sTNF-alpha-induced cell death and had no detectable NF-kappaB activation.
      Consistently, siRNA-mediated tmTNF-alpha knockdown blocked NF-kappaB activation
      and rendered MDA-MB-231 sensitive. To test our hypothesis that TNF-LS may play an
      important role in determining the sensitivity of tumor cells to sTNF-alpha, we
      stably transfected MCF-7 cells with TNF-LS. We found that transfection of TNF-LS
      or wild-type TNF-alpha containing LS constitutively activated NF-kappaB and
      conferred the cytotoxic resistance of MCF-7 cells, while transfection of a mutant
      tmTNF-alpha lacking the cytoplasmic segment of LS neither activated NF-kappaB nor
      affected the sensitivity. However, NF-kappaB inhibitor PDTC suppressed NF-kappaB
      activation and reconstituted sensitivity of TNF-LS/MCF-7 cells. To check whether
      TNF-LS is required to be cleaved or internalized for NF-kappaB activation to
      occur, we used signal peptide peptidase inhibitor (Z-LL)(2)-ketone and receptor
      internalization inhibitor MDC to treat cells. Interestingly, both inhibitors
      increased TNF-LS expression on the cell surface and enhanced NF-kappaB
      activation. These results indicate that membrane-anchored TNF-LS contributes to
      constitutive activation of NF-kappaB and resistance to sTNF-alpha-induced cell
      death. Therefore, TNF-LS appears to be responsible for tmTNF-alpha-induced
      resistance in the breast cancer cells.

PMID- 18618240
TI  - Expression of coxsackie-adenovirus receptor is related to estrogen sensitivity in
      breast cancer.
AB  - This study analyzes the relationship between coxsackie-adenovirus receptor (CAR)
      expression (transmembrane and soluble isoforms) and hormone sensitivity in 95
      breast cancers. Furthermore, prognostic significance of the expression of the
      various CAR isoforms was investigated. In addition, inducibility of CAR
      expression by estradiol and tamoxifen was assessed in various breast cancer cell
      lines. Expression of transmembrane CAR (hCAR) highly correlated with estrogen
      receptivity, but was independent of the expression of progesterone receptor (PR).
      Furthermore, hCAR expression was significantly higher in tumors with low-grade
      malignancy. However, no relationship between hCAR expression and tumor size,
      lymph node status, or survival was revealed. In the hormone receptor-positive
      breast cancer cell line T47-D expression of hCAR and its soluble isoforms was
      increased by treatment with estradiol and tamoxifen. In contrast, no induction of
      either CAR isoform was achieved in receptor-negative cell lines. Furthermore,
      enhancement of hCAR expression was significantly greater when cells were treated
      with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) than when
      treated with estradiol or tamoxifen. Moreover, sensitivity to TSA induction of
      hCAR was considerably greater in receptor-positive than in receptor-negative cell
      lines. No additive effect on CAR expression was found when TSA was combined with
      either estradiol or tamoxifen. In conclusion, the so far undescribed association
      between estrogen receptivity and the expression of hCAR in breast cancer seems to
      not only reflect a phenotype of low malignancy, but expression of hCAR may also
      be directly influenced by ER-specific ligands.

PMID- 18618241
TI  - Small angle neutron scattering as sensitive tool to detect ligand-dependent shape
      changes in a plant lectin with beta-trefoil folding and their dependence on the
      nature of the solvent.
AB  - The galactoside-specific Viscum album L. agglutinin (VAA) is a potent biohazard
      akin to ricin and a mitogen for immune and tumor cells. These activities depend
      on cell surface binding to glycans. It is an open question whether the process of
      ligand binding alters the lectin's shape. Small angle neutron scattering (SANS)
      experiments revealed that the carbohydrate ligand lactose induced a decrease of
      the radius of gyration of dimeric VAA from 54.5 +/- 1 to 49.5 +/- 1 A in water.
      Apparently, VAA in aqueous solution and at the concentrations tested at 3.6 mg/ml
      and above adopts a compacted structure as response to ligand binding. In contrast
      to the behavior in aqueous solution, lactose binding in DMSO resulted in an
      increase of the lectin's radius of gyration from 49 +/- 1 to 55.5 +/- 1 A.
      Because shape changes may be reflected in the thermostability of the protein,
      this parameter was examined by activity assays of protein exposed to 60 degrees C
      and 70 degrees C and by differential scanning calorimetry (DSC). In line with the
      lactose-induced conformational alterations revealed by the SANS experiments,
      lactose presence enhanced the thermostability of VAA in water. Thus, binding of
      the carbohydrate ligand in solution can entail changes in shape and
      thermostability in the case of the tested plant lectin.

PMID- 18618243
TI  - The effects of caffeine on L-arginine metabolism in the brain of rats.
AB  - In our study, the short-term effects of caffeine on L-arginine metabolism in the
      brains of rats were investigated. Caffeine was given orally at two different
      doses: 30 mg/kg and 100 mg/kg (a high non-toxic dose). Brain tissue arginase
      activity in rats from the caffeine-treated groups decreased significantly
      compared with the control group. Malondialdehyde (MDA) levels in the brain tissue
      and serum of animals in the caffeine groups also decreased significantly. Brain
      tissue and serum nitric oxide (NO) levels increased significantly after caffeine
      administration. Tumor necrosis factor-alpha (TNF-alpha) levels were also
      investigated in rat serum, but there was no statistically significant difference
      between the TNF-alpha levels of the caffeine-treated rats groups and the control
      rats. Our study indicates that brain arginase activity decreases after caffeine
      administration at doses of 30 mg/kg and 100 mg/kg. As a result, we can say that
      arginine induces production of NO in the organism.

PMID- 18618242
TI  - Treatment of sleep disordered breathing in congestive heart failure.
AB  - In patients with congestive heart failure, sleep disordered breathing occurs
      commonly and is associated with an increased mortality. In addition to central
      sleep apnea (Cheyne-Stokes respiration), obstructive sleep apnea is more
      prevalent in patients with congestive heart failure than in the general
      population. As a result, a number of treatments have been investigated, with
      varying results. While many therapies may improve the severity of sleep
      disordered breathing, only positive pressure ventilation has been shown to
      improve cardiac function. Newer forms of positive pressure ventilation, such as
      adaptive servo-ventilation, appear to be even more effective at correcting
      central sleep apnea. Whether any of these treatments have an effect on transplant
      free survival is presently unknown and awaits further study.

PMID- 18618244
TI  - Metalloproteinase's activity and oxidative stress in mild cognitive impairment
      and Alzheimer's disease.
AB  - Matrix metalloproteinases (MMPs) and oxidative stress have been implicated in
      neurological diseases such as Alzheimer's disease (AD). Plasma MMP-2 and MMP-9
      activities were assessed in Mild Cognitive Impairment (MCI) and AD subjects
      compared with aged-matched controls, and subsequently analysed in relation to
      oxidative stress markers. Both MMP-2 and MMP-9 showed no significant changes
      versus control subjects. Plasma glutathione peroxidase Se-dependent (GPx-Se)
      activity and malondialdehyde (MDA) levels were higher in AD than in controls (P <
      0.05), suggesting a role for GPx-Se in controlling oxidative stress in AD.
      Negative correlations were observed between MMPs and MDA in AD and MCI patients
      (P < 0.05). In conclusion, oxidative stress events did not include activation of
      MMPs and this similar pattern in AD and MCI suggests that both are biochemically
      equivalent.

PMID- 18618245
TI  - Post-translational modifications of chicken myelin basic protein charge
      components.
AB  - Purified myelin basic protein (MBP) from various species contains several post
      translationally modified forms termed charge components or charge isomers.
      Chicken MBP contains four charge components denoted as C1, C2, C3 and C8. (The C8
      isomer is a complex mixture and was not investigated in this study.) These
      findings are in contrast to those found for human, bovine and other mammalian
      MBP's. Mammalian MBP's, each of which contain seven or eight charge components
      depending on the analysis of the CM-52 chromatographic curves and the PAGE gels
      obtained under basic pH conditions. Chicken MBP components C1, C2 and C3 were
      treated with trypsin and endoproteinase Glu-C. The resulting digests were
      analyzed by capillary liquid chromatography combined with either an ion trap
      tandem mass spectrometer or with a Fourier transform ion cyclotron resonance mass
      spectrometer. This instrumentation permitted establishing the amino acid
      composition and the determination of the post-translational modifications for
      each of the three charge components C1-C3. With the exception of N-terminal
      acetylation, the post-translational modifications were partial. The C1 component
      lacks any phosphorylated sites, a finding in agreement with the analysis of other
      MBP species. It also had a single methylation at R105 as did the components C2
      and C3. The C2 component contains ten phosphorylated sites (S7, S18, S33, S64,
      S73, T96, S113, S141, S164, and S168), and modified arginine to citrulline
      residues at R24, and R165. Component C3 contains eight phosphorylated sites (S7,
      S33, S64, T96, S113, S141, S164, and S168), and citrulline residues at Arginine
      41, R24 and R165. Partial deamidation of glutamine residues Q71, Q101 and Q146
      were present in addition to asparagine N90 that was found in all three charge
      components. The glutamine at residue 3 is partially deamidated in isomers C1 and
      C2, whereas glutamine 74 and asparagine 83 were found not to be deamidated.
      Comparison of the PTM's of MBP's isolated from several vertebrate species reveals
      marked differences in their phosphate content. Chicken MBP does not share any
      phosphorylated sites with dogfish MBP; However, it does contain phosphorylated
      serine and threonine residues in common with mammalian MBP.

PMID- 18618246
TI  - Acupuncture for the treatment of drug addiction.
AB  - Over the last three decades there has been an increasing interest in acupuncture
      treatment of substance abuse around the world. Three important steps can be
      identified in this field. Dr. Wen of Hong Kong was the first (1972) to report
      that acupuncture at 4 body points and 2 ear points combined with electrical
      stimulation can relieve opioid withdrawal signs in the addicts. The second major
      step was made by Dr. M. Smith in New York, the head of the National Acupuncture
      Detoxification Association (NADA) of the USA, who finalized a protocol (1985),
      using only ear points without electrical stimulation for the treatment of drug
      abuse. The recent advance in this field was made by Dr. Han of the Peking
      University, Beijing, who characterized a protocol (2005), using electrical
      stimulation of identified frequencies on body points to ameliorate heroin
      withdrawal signs and prevent relapse of heroin use. In this review, the efficacy
      of acupuncture and related techniques for the treatment of drug dependence in
      experimental settings and clinical practice will be reviewed, and the possible
      mechanisms underlying this effect be discussed.

PMID- 18618247
TI  - Effect of 5-azacytidine on the methylation aspects of NMDA receptor NR2B gene in
      the cultured cortical neurons of mice.
AB  - Our previous study revealed that the exposure of the drug 5-Azacytidine and
      ethanol to the cultured cortical neurons of mice causes demethylation of cytosine
      residues in the CpG island of the NMDA receptor NR2B gene (Marutha Ravindran and
      Ticku, Mol Brain Res 121:19-27, 2004). In the present study, we further analyzed
      methylation in the CpG island with various concentration frame and time frame of
      exposure of the cultured cortical neurons with 5-azacytidine to identify whether
      methylation in the NR2B gene is site specific or region specific. Methylation was
      studied by digesting the genomic DNA with methylation sensitive HpaII, MspI, AciI
      or HhaI enzyme following the exposure of cultured cortical neurons of mice with 5
      azacytidine by performing PCR and Southern hybridization. We observed
      demethylation of DNA at 1, 3 and 5 muM concentrations of 5-azacytidine in the
      regions (5982-6155), (6743-7466) and at 3 and 5 muM concentrations of 5
      azacytidine used in the region (6477-6763). Similarly in the time frame study
      with 5-azacytidine, demethylation of DNA was observed at 24 h and 36 h of
      incubation with 5-azacytidine in the regions (5982-6155), (6743-7466) and at 36 h
      of incubation with 5-azacytidine used in the region (6477-6763). Our experimental
      results demonstrate that the methylation in the CpG islands of the NR2B gene may
      not be site specific or region specific in the cultured cortical neurons of mice.

PMID- 18618248
TI  - The expression of tumor necrosis factor-alpha (TNF-alpha) by the intrathecal
      injection of lipopolysaccharide in the rat spinal cord.
AB  - The proinflammatory and lipopolysaccharide (LPS)-inducible cytokine tumor
      necrosis factor alpha (TNF-alpha) has been shown to enhance primary sensory
      nociceptive signaling. However, the precise cellular site of TNF-alpha synthesis
      is still a matter of controversy. Therefore, we focused our study on TNF-alpha
      protein synthesis and expression patterns in spinal dorsal horn of naives and
      rats under intrathecal challenge with LPS. The enzyme-linked immunosorbent
      (ELISA) assay showed that the protein level of TNF-alpha reached peak at 8 h.
      Double immunofluorescence revealed that LPS-induced expression of TNF-alpha
      exclusively located in a subpopulation of microglia, which increased at 8 h in
      the rat spinal dorsal horn (the injected side). Positive staining of TNF receptor
      1 (TNFR1) were also found in microglia. These observations have demonstrated the
      production of this proinflammatory cytokine by central nerve glia especially
      microglia. Synthesized TNF-alpha might directly act on microglia via TNFR1, but
      the inherent mechanisms remain unknown. Further studies are needed to confirm the
      pathogenic role of tumor necrosis factor in the early stage of inflammation.

PMID- 18618249
TI  - Validation of prognostic indices using the frailty model.
AB  - A major issue when proposing a new prognostic index is its generalisibility to
      daily clinical practice. Validation is therefore required. Most validation
      techniques assess whether "on average" the results obtained by the prognostic
      index in classifying patients in a new sample of patients are similar to the
      results obtained in the construction set. We introduce a new important aspect of
      the generalisibility of a prognostic index: the heterogeneity of the prognostic
      index risk group hazard ratios over different centers. If substantial variability
      between centers exists, the prognostic index may have no discriminatory
      capability in some of the centers. To model such heterogeneity, we use a frailty
      model including a random center effect and a random prognostic index by center
      interaction. Statistical inference is based on a Bayesian approach using a
      Laplacian approximation for the marginal posterior distribution of the variances
      of the random effects. We investigate different ways to summarize the information
      available from this marginal posterior distribution. Our approach is applied to a
      real bladder cancer database for which we demonstrate how to investigate and
      interpret heterogeneity in prognostic index effect over centers.

PMID- 18618250
TI  - Predictive factors associated with the progression to hepatic failure caused by
      lamivudine-resistant HBV.
AB  - The aims of this study were to select the patients with a potential for
      progression to hepatic failure due to lamivudine-resistant HBV and to standardize
      the treatment for patients with lamivudine-resistant HBV. Patients (n = 47) with
      reactivated hepatitis due to lamivudine-resistant HBV were classified into two
      groups, with and without potential for progression to hepatic failure, according
      to the criteria using the data of serum bilirubin level and prothrombin activity
      after the reactivated hepatitis. Multivariate analysis showed that prothrombin
      activity at the initiation of lamivudine therapy was related to the deterioration
      of the liver function after the emergence of lamivudine-resistant HBV (P =
      0.0025, 95%CI 0.8269-0.9601). We assume that earlier additional or substitutive
      treatment with other antiviral agent, such as adefovir dipivoxil, should be
      recommended when the lamivudine-resistant HBV is detected in patients with the
      history of decompensated liver disease before the administration of lamivudine,
      even when hepatitis has not been reactivated yet.

PMID- 18618251
TI  - Site specific delivery of microencapsulated fish oil to the gastrointestinal
      tract of the rat.
AB  - The aim of this study was to design food grade matrices to deliver
      microencapsulated fish oil to the large bowel of the rat where the potential
      exists to retard inflammation and cancer development. Digestion in simulated
      gastric fluid and intestinal fluid demonstrated that only 4-6% of oil was
      released from the following dried emulsion formulations: 50% fish oil
      encapsulated in heated casein-glucose-dried glucose syrup (1:1:1) (Cas-Glu-DGS
      50); 25% fish oil in casein-modified resistant starch (Hylon VII) (1:1) (Cas
      Hylon-25); or 25% fish oil in Cas-Glu-Hylon (1:1:1) (Cas-Glu-Hylon-25). A short
      term gavage study (0-12 h) with fish oil and Cas-Glu-DGS-50 demonstrated the
      appearance of fish oil long chain (LC) n-3 polyunsaturated fatty acids (PUFA)
      into the plasma indicating specific small intestinal absorption with little LC n
      3 PUFA reaching the large bowel. In a 2-week-long term, daily gavage study, the
      bioavailability of fish oil and fish oil in Cas-Glu-DGS-50 or Cas-Hylon-25
      demonstrated that fish oil and Cas-Glu-DGS-50 LC n-3 PUFA were incorporated into
      the tissue of the small intestine and colon, whereas Cas-Hylon-25 was resistant
      to degradation in the small intestine. The use of modified Hylon VII for targeted
      colonic delivery was confirmed in the final short-term gavage study (0-14 h)
      using Cas-Glu-Hylon-25 with [(14)C]-trilinolenin as a marker incorporated into
      the microcapsules, where up to 60% of the labeled oil reached the large bowel.
      Depending on the microencapsulating matrix employed, fish oil can be delivered
      selectively to the small intestine or to a high degree to the large bowel.

PMID- 18618252
TI  - Vitamin D receptor gene polymorphisms and the risk of colorectal cancer in a
      Chinese population.
AB  - OBJECTIVE: The purpose was to investigate single nucleotide polymorphism of the
      vitamin D receptor gene and its possible relationship with colorectal cancer
      (CRC) in a Chinese population. METHODS: The vitamin D receptor (VDR) genotypes
      were determined by polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) using endonuclease BsmI and FokI, and direct sequencing
      in 400 Chinese people, comprised of 200 CRC patients and 200 controls from the
      same area in China. RESULTS: The distribution of alleles (F/f) and genotypes
      (FF/Ff/ff) of the FokI had no significant difference between CRC patients and
      normal controls (P > 0.05), while that of the B allele and the BB genotype of the
      BsmI in CRC patients was significantly lower compared with the control group
      (0.1625 versus 0.740, P < 0.05, OR = 0.068, 95% CI: 0.048-0.096 and 0.060 versus
      0.590, P < 0.05, OR = 0.015, 95% CI: 0.007-0.032). CONCLUSION: The BB genotype of
      the VDR BsmI variant was significantly associated with a decreased risk of CRC in
      a Chinese population, while the VDR FokI polymorphism was not significantly
      associated with it.

PMID- 18618253
TI  - Serum levels of keratin-18 fragments [tissue polypeptide-specific antigen (TPS)]
      are correlated with hepatocyte apoptosis in alcoholic hepatitis.
AB  - Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30
      neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide
      specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor
      marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The
      aim of this study was to investigate the possible relationship of TPS levels with
      hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic
      hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was
      evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial
      immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis
      than in patients with fatty liver. There was a significant correlation between
      the apoptotic score and TPS levels. The correlation of the apoptotic score with
      TPS levels was stronger than with standard liver tests. Serum TPS may be a marker
      of apoptosis in alcoholic hepatitis.

PMID- 18618254
TI  - Agenesis of the dorsal pancreas and associated diseases.
AB  - BACKGROUND: Agenesis of the dorsal pancreas is a very rare congenital pancreatic
      malformation and is associated with some other diseases. METHODS: A PubMed search
      revealed 53 cases of agenesis of the dorsal pancreas. RESULTS: In 28 patients
      with this congenital malformation hyperglycemia was demonstrated, 27 had
      abdominal pain, 16 had pancreatitis, 14 had an enlarged or prominent pancreatic
      head visible on computed tomography, and in a few cases, polysplenia, which may
      occur with various congenital anomalies of visceral organs, was described.
      CONCLUSIONS: Difficulties involved in obtaining a firm diagnosis have led to a
      variety of terms being used to describe this congenital disease. Diagnosis of
      agenesis of the dorsal pancreas is inconclusive without demonstration of the
      absence of the dorsal pancreatic duct. Here we describe the embryological
      development of the pancreas, the so-far known cases of agenesis of the dorsal
      pancreas with associated medical problems, and the diagnostic measures to find
      the right conclusions.

PMID- 18618256
TI  - Acute upper gastrointestinal bleeding in central Greece: the role of clinical and
      endoscopic variables in bleeding outcome.
AB  - The objectives of this work were to portray the incidence of upper
      gastrointestinal bleeding in central Greece and to define subsets at higher risk
      of poor outcome or death. Two hundred and sixty-four cases were recorded. The
      incidence was 116 per 100,000 per year (95% CI: 102-130). Re-bleeding was noted
      in 7.9% of patients. The case fatality was 7.2% and population mortality 8 per
      100,000 per year (95% CI: 4-12). Independently significant risk factors for re
      bleeding were stigmata of bleeding at endoscopy (OR: 3.11; 95% CI: 1.06-9.13, P =
      0.04), smoking (OR: 3.39; 95% CI: 1.08-10.62, P = 0.03), and the use of anti
      coagulant drugs (OR: 2.64; 95% CI: 1.00-7.13, P = 0.05), while the independently
      significant risk factor for death was re-bleeding (OR: 5.74; 95% CI: 1.40-23.52,
      P = 0.03). We conclude that patients with stigmata of bleeding at endoscopy and
      on anti-coagulant therapy should be under close surveillance because of the
      higher risk of re-bleeding. Smoking also increases the risk of re-bleeding.
      Patients with re-bleeding episodes must be managed intensively because of the
      higher risk of death.

PMID- 18618255
TI  - On the use of herbal medicines in management of inflammatory bowel diseases: a
      systematic review of animal and human studies.
AB  - Because of potential adverse events and lack of effectiveness of standard
      therapies, the use of complementary and alternative medicines (CAM), particularly
      of herbal therapies, for inflammatory bowel disease (IBD) is increasing. Results
      from the use of herbal therapies for managing IBD are promising, and no serious
      adverse events have been reported from them. Herbal therapies show their benefit
      in managing IBD by different mechanisms such as immune system regulation,
      antioxidant activity, inhibition of leukotriene B4, inhibition of nuclear factor
      kappa B (NF-kappaB), and antiplatelet activity. In this paper, all reported
      herbal therapies established in animal IBD models or used for managing human IBD
      are systematically reviewed and their possible mechanisms of action discussed.
      Conducting clinical trials with high quality and validity (randomized, double
      blinded, controlled, on a large number of patients) to obtain more conclusive
      results about the use of herbal therapies in IBD is recommended.

PMID- 18618257
TI  - A novel method for study of gastric mechanical functions in conscious mice.
AB  - A novel method has been developed for simultaneous study of gastric emptying,
      antral motility, and gastric muscle tone in conscious mice. Intragastric pressure
      was measured during infusion of an X-ray-opaque, viscous meal through a
      chronically implanted gastric fistula (0.25 ml/min). Compared with vehicle
      treatment, molsidomine (nitric oxide donor) and atropine (muscarinic receptor
      antagonist) treatment significantly reduced the area under the intragastric
      pressure curve (AUC) by 37 +/- 4% and 35 +/- 3%, respectively, (mean +/- S.E.M.)
      whereas N (G)-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase
      inhibitor) significantly increased the AUC by 20 +/- 3%. Atropine also
      significantly reduced the frequency and amplitude of stomach contraction-induced
      intragastric pressure waves while molsidomine only reduced the frequency. Gastric
      emptying, as assessed by X-ray imaging, was significantly delayed after L-NAME
      and atropine treatment. This methodology is the first to enable simultaneous
      assessment of gastric emptying, antral motility, and gastric tone in conscious
      mice and confirmed the important role of nitrergic and cholinergic innervation.

PMID- 18618258
TI  - Gallbladder sarcoma: a clinicopathological study of seven cases from the UK and
      Austria with emphasis on morphological subtypes.
AB  - BACKGROUND: Primary sarcoma of the gallbladder (PGBS) is rare, with only 40 cases
      reported in the literature. Most of these have been diagnosed as leiomyosarcoma.
      We aimed to evaluate the histological features of a case series of this rare
      tumor and correlate these with clinical features. DESIGN: Cases recorded as
      "gallbladder sarcoma" from different institutes were reviewed and the
      clinicopathological features of these cases were recorded. Only primary
      gallbladder wall mesenchymal tumors were included. Epithelial tumors, mixed
      tumors (carcinosarcoma or sarcomatoid carcinoma), and tumors extending into the
      gallbladder from the abdomen or sarcoma with other known primaries were
      specifically excluded. RESULT: PGBS occurred in one male and six females with a
      median age of 70 (range 64-82) years. Patients presented with acute or chronic
      cholecystitis, abdominal pain, weight loss, and pruritus. They were generally
      found to have elevated alkaline phosphatase and bilirubin, and leukocytosis.
      Tumors ranged from 1.1 to 4 cm with a median size of 3 cm. Most PGBS arose in the
      body but one arose in the fundus. All tumors were associated with ulcerated
      mucosa. Based on morphological and immunohistochemical features of the PGBS,
      there were three myxofibrosarcomas (malignant fibrous histiocytoma, MFH,
      storiform pleomorphic), one leiomyosarcoma (LMS), one angiosarcoma (AS), and two
      liposarcomas (LS). All patients received cholecystectomy and three received
      adjuvant chemotherapy. Follow-up revealed that six patients died of the disease 6
      weeks to 2 years after diagnosis and one died of unrelated causes. CONCLUSION:
      PGBS are rare and mainly occur in the gallbladder body in middle-aged females.
      They generally present with acute cholecystitis and have a very poor prognosis. A
      variety of sarcoma types are found with MFH being the predominant variant.

PMID- 18618259
TI  - Diagnostic and therapeutic approach to pancreatic cancer-associated
      gastroparesis: literature review and our experience.
AB  - BACKGROUND: Patients with unresectable pancreatic carcinoma often present with
      early satiety, nausea, and vomiting without evidence of mechanical obstruction,
      mucosal disease, or metabolic abnormality. This condition is well described in
      the literature and is thought to result from pancreatic cancer-associated
      gastroparesis (PCAG). No clinical guideline is available for diagnosing and
      managing this rare disease. OBJECTIVE: To propose an algorithm for diagnosing and
      managing patients with PCAG based on a literature review and our clinical
      experience. METHODS: A comprehensive review was conducted of literature on the
      subject from 1966 to 2005, and retrospective analysis was performed for patients
      with PCAG who presented to the University of Iowa Hospitals and Clinics (Iowa
      City, IA, USA) during the period 1998-2005. RESULTS: Literature on an optimal
      diagnostic and therapeutic approach to PCAG is lacking. There are only two small
      case series and one case report regarding management of PCAG. Extensive chart
      review only identified two patients who met the diagnostic criteria of PCAG. We
      propose performing routine upper GI series and esophagogastroduodenoscopy on all
      patients with pancreatic cancer who present with nausea and vomiting, to rule out
      obstruction and mucosal disease. If there is no obstruction or mucosal disease,
      we do not recommend further workup. Prokinetic agents are the first line therapy
      for PCAG. In refractory cases, percutaneous endoscopic gastrostomy with jejunal
      extension may be considered in selected patients who respond to nasojejunal
      decompression. CONCLUSIONS: We propose a time-effective and useful strategy for
      diagnosing and managing patients with PCAG. We also define the diagnostic end
      point for this difficult to manage condition.

PMID- 18618260
TI  - Neurite outgrowth on a DNA crosslinked hydrogel with tunable stiffnesses.
AB  - Mechanical cues arising from extracellular matrices greatly affect cellular
      properties, and hence, are of significance in designing biomaterials. In this
      study, a DNA crosslinked hydrogel was employed to examine cellular responses of
      spinal cord neurons to substrate compliances. Using DNA as crosslinkers in
      polymeric hydrogel formation has given rise to a new class of hydrogels with a
      number of attractive properties (e.g., reversible gelation and controlled
      crosslinking). Here, it was demonstrated that by varying length of crosslinker,
      monomer concentration, and level of crosslinking, DNA gel stiffnesses span from
      approximately 100 Pa to 30 kPa. Assessment of neurite outgrowth on functionalized
      DNA gels showed that although primary dendrite length is not significantly
      affected, spinal cord neurons extend more primary dendrites and shorter axons on
      stiffer gels. Additionally, a greater proportion of neurons have more primary
      dendrites and shorter axons on stiffer gels. There is a pronounced reduction in
      focal adhesion kinase (FAK) when neurons are exposed to stiffer substrates,
      suggesting its involvement in neuronal mechanosensing and neuritogenesis in
      response to stiffness. These results demonstrate the importance of mechanical
      aspects of the cell-ECM interactions, and provide guidance for the design of
      mechanical properties of bio-scaffolds for neural tissue engineering
      applications.

PMID- 18618261
TI  - Adaptive match filter based method for time vs. amplitude characterization of
      microvolt ECG T-wave alternans.
AB  - To develop a new method for non-invasive identification of patients prone to
      ventricular tachyarrhythmia and sudden cardiac death, an adaptive match-filter
      (AMF) was applied to detect and characterize T-wave alternans (TWA) in 200
      coronary artery diseased (CAD) patients compared with 176 healthy (H) subjects.
      TWA was characterized in terms of duration (TWAD), amplitude (TWAA), and
      magnitude (TWAM, defined as the product of TWAD times TWAA). A criterion derived
      from these parameters, estimated over the H-population, allowed discrimination
      between a risk (TWA+) and a normality (NO TWA) zone in the TWAD-TWAA plane. To
      gain further ability to discriminate among different risk levels, the TWA+ zone
      was divided into four sub-zones respectively characterized by low duration and
      low amplitude (LDLA), low duration and high amplitude (LDHA), high duration and
      low amplitude (HDLA), and high duration and high amplitude (HDHA). With our
      methodology, 21 CAD-patients (10.5%) were identified as TWA+, 9 falling in the
      LDLA zone, 4 in the HDLA, 7 in the LDHA, and 1 in the HDHA. These results are in
      agreement with clinical expectations and pave the way to further clinical follow
      up studies finalized to analyze pathophysiological implications and risk factors
      associated to each TWA+ zone.

PMID- 18618262
TI  - Impact of ambulation in wearable-ECG.
AB  - Ambulatory ElectroCardioGram (ECG) analysis is adversely affected by motion
      artifacts induced due to body movements. Knowledge of the extent of motion
      artifacts could facilitate better ECG analysis. In this paper, our purpose is to
      determine the impact of body movement kinematics on the extent of ECG motion
      artifact by defining a notion called impact signal. Two approaches have been
      adopted in this paper to validate our experiments. One of them involves measuring
      local acceleration using motion sensors at appropriate body positions, in
      conjunction with the ECG, while performing routine activities at different
      intensity levels. The other method consists of ECG acquisition during Treadmill
      testing at controlled speeds and fixed duration. Data has been acquired from both
      healthy subjects as well as patients with suspected cardio-vascular disorders. In
      case of patients, the treadmill tests were carried out under the supervision of a
      cardiologist. We demonstrate that the impact signal shows a proportional increase
      with the increasing activity levels. The measured accelerations obtained are also
      found to be well correlated with the impact signal. The impact analysis thus
      indicates the suitability of the proposed method for quantification of body
      movement kinematics from the ECG signal itself, even in the absence of any
      accelerometer sensors. Such quantification would also help in automatic
      documentation of patient activity levels, which could aid in better
      interpretation of ambulatory ECG.

PMID- 18618263
TI  - Service use patterns for adolescents with ADHD and comorbid conduct disorder.
AB  - Service use patterns and costs of youth diagnosed with attention
      deficit/hyperactivity disorder (ADHD) and comorbid conduct disorder (CD) were
      assessed across adolescence (ages 12 through 17). Featured service sectors
      include mental health, school services, and the juvenile justice system. Data are
      provided by three cohorts from the Fast Track evaluation and are based on parent
      report. Diagnostic groups are identified through a structured assessment. Results
      show that public costs for youth with ADHD exceed $40,000 per child on average
      over a 6-year period, more than doubling service expenditures for a non-ADHD
      group. Public costs for children with comorbid ADHD and CD double the costs of
      those with ADHD alone. Varying patterns by service sector, diagnosis, and across
      time indicate different needs for youth with different conditions and at
      different ages and can provide important information for prevention and treatment
      researchers.

PMID- 18618264
TI  - Characteristics, service experiences, and outcomes of transition-aged youth in
      systems of care: programmatic and policy implications.
AB  - This article examines data for 8,484 transition-aged youth (TAY) in different age
      groups who received services in 45 federally funded systems of care between 1997
      and 2006. Data from the national evaluation of these systems of care were used to
      compare descriptive and clinical characteristics at intake of TAY aged 14-15, 16
      17, and 18 years, and service use and outcomes of TAY aged 14-15 and 16-17 at 6
      and 12 months after system of care intake. Few studies have examined outcomes of
      TAY. The large national evaluation database provides a unique opportunity to
      examine outcomes for TAY in relation to increases in age. Results revealed
      differences in severity and type of behavioral and emotional problems, living
      situations, access to Medicaid, service use, and outcomes among younger and older
      youth. Findings support the need to enhance access to services for older TAY and
      to customize services to the unique needs of each age group.

PMID- 18618265
TI  - Impact of court-mandated substance abuse treatment on clinical decision making.
AB  - California's Proposition 36 offers nonviolent drug offenders community-based
      treatment as an alternative to incarceration or probation without treatment. The
      study objective was to examine how substance abuse treatment providers perceive
      the impact of Proposition 36 on their clinical decision making. Program surveys
      were completed by 115 treatment programs in five California counties to assess
      the impact of the law on clinical decision making, and five focus groups were
      conducted with 37 treatment providers to better understand their perspectives.
      Compared to residential programs, outpatient programs reported that the policy
      impacted them to a greater extent in terms of drug testing, reporting to criminal
      justice personnel, and determining client discharge. Providers in the focus
      groups particularly highlighted their changing roles in assessing clients'
      treatment needs and determining the best routes of care for them. The findings
      indicate that alternate strategies for determining treatment placement and
      continuing care should be developed.

PMID- 18618266
TI  - Adolescent satisfaction with brief motivational enhancement for alcohol abuse.
AB  - Although many investigations point to the importance of treatment satisfaction
      and working alliance as predictors of treatment engagement and outcome, few
      studies have closely examined these issues among adolescents. This study
      investigates satisfaction among a nonclinical adolescent sample participating in
      a school-based alcohol-prevention program. Adolescents self-selected to one of
      three formats: individual, group, and website. Three hundred nineteen
      satisfaction measures completed at the time of each participant's final session
      were used for analyses. Hierarchical regression analyses examined predictors of
      consumer satisfaction. In general, greater participation in the program was
      significantly related to satisfaction. Students who participated in the group and
      individual formats reported greater satisfaction than students who participated
      in the website format. Current alcohol users were less satisfied with the session
      focusing on how experimental use can lead to problem use; lifetime abstainers
      were more satisfied with the session focusing on stress and coping. These
      analyses have implications for informing future adolescent school-based
      interventions for alcohol problems.

PMID- 18618267
TI  - The 6th world meeting on pharmaceutics, biopharmaceutics and pharmaceutical
      technology (PBP meeting) April 7-10, 2008, Barcelona, Spain.

PMID- 18618268
TI  - A. fulgidus SRP54 M-domain.

PMID- 18618269
TI  - Revisiting the relation between species diversity and information theory.
AB  - The Shannon information function (H) has been extensively used in ecology as a
      statistic of species diversity. Yet, the use of Shannon diversity index has also
      been criticized, mainly because of its ambiguous ecological interpretation and
      because of its relatively great sensitivity to the relative abundances of species
      in the community. In my opinion, the major shortcoming of the traditional
      perspective (on the possible relation of species diversity with information
      theory) is that species need for an external receiver (the scientist or
      ecologist) to exist and transmit information. Because organisms are self
      catalized replicating structures that can transmit genotypic information to
      offspring, it should be evident that any single species has two possible states
      or alternatives: to be or not to be. In other words, species have no need for an
      external receiver since they are their own receivers. Therefore, the amount of
      biological information (at the species scale) in a community with one only
      species would be log2(2)1 = 1 species, and not log2(1) = 0 bits as in the
      traditional perspective. Moreover, species diversity appears to be a monotonic
      increasing function of log2(2)S (or S) when all species are equally probable (S
      being species richness), and not a function of log2 S as in the traditional
      perspective. To avoid the noted shortcoming, we could use 2(H) (instead of H) for
      calculating species diversity and species evenness (= 2(H)/S). However, owing to
      the relatively great sensitivity of H to the relative abundances of species in
      the community, the value of species dominance (= 1 - 2(H)/S) is unreasonably high
      when differences between dominant and subordinate species are considerable,
      thereby lowering the value of species evenness and diversity. This unsatisfactory
      behaviour is even more evident for Simpson index and related algorithms. I
      propose the use of other statistics for a better analysis of community structure,
      their relationship being: species evenness + species dominance = 1; species
      diversity x species uniformity = 1; and species diversity = species richness x
      species evenness.

PMID- 18618270
TI  - Escherichia coli FtnA acts as an iron buffer for re-assembly of iron-sulfur
      clusters in response to hydrogen peroxide stress.
AB  - Iron-sulfur clusters are one of the most ubiquitous redox centers in biology.
      Ironically, iron-sulfur clusters are highly sensitive to reactive oxygen species.
      Disruption of iron-sulfur clusters will not only change the activity of proteins
      that host iron-sulfur clusters, the iron released from the disrupted iron-sulfur
      clusters will further promote the production of deleterious hydroxyl free
      radicals via the Fenton reaction. Here, we report that ferritin A (FtnA), a major
      iron-storage protein in Escherichia coli, is able to scavenge the iron released
      from the disrupted iron-sulfur clusters and alleviates the production of hydroxyl
      free radicals. Furthermore, we find that the iron stored in FtnA can be retrieved
      by an iron chaperon IscA for the re-assembly of the iron-sulfur cluster in a
      proposed scaffold IscU in the presence of the thioredoxin reductase system which
      emulates normal intracellular redox potential. The results suggest that E. coli
      FtnA may act as an iron buffer to sequester the iron released from the disrupted
      iron-sulfur clusters under oxidative stress conditions and to facilitate the re
      assembly of the disrupted iron-sulfur clusters under normal physiological
      conditions.

PMID- 18618271
TI  - Evolutionary relationship between defensins in the Poaceae family strengthened by
      the characterization of new sugarcane defensins.
AB  - Plant defensins are small (45-54 amino acids), highly basic, cysteine-rich
      peptides structurally related to defensins of other organisms, including insects
      and mammals. Small putative proteins (MW < 10 kDa) containing eight cysteines
      were screened based on the sugarcane expressed sequence tag (EST) database. We
      selected ORFs that exhibited 25-100% similarity in primary sequence with other
      defensins in the NCBI database and that contained eight cysteines. This
      similarity is sufficient for folding prediction, but not enough for biological
      activity inference. Six putative defensins (Sd1-6) were selected, and activity
      assays showed that recombinant Sd1, Sd3 and Sd5 are active against fungi, but not
      against bacteria. Structural characterization, based on circular dichroism (CD)
      and nuclear magnetic resonance (NMR) spectroscopy showed that the structures of
      these Sds were compatible with alpha/beta proteins, a feature expected for plant
      defensins. Phylogenetic analysis revealed that sugarcane defensins could clearly
      be grouped within defensins from Poaceae family and Andropogoneae tribe. Our work
      demonstrates that defensins show strong conservation in the Poaceae family and
      may indicate that the same conservation occurs in other families. We suggest that
      evolutionary relationships within plant families can be used as a procedure to
      predict and annotate new defensins in genomes and group them in evolutionary
      classes to help in the investigation of their biological function.

PMID- 18618272
TI  - Functional analysis of LjSUT4, a vacuolar sucrose transporter from Lotus
      japonicus.
AB  - Sucrose transporters in the SUT family are important for phloem loading and
      sucrose uptake into sink tissues. The recent localization of type III SUTs AtSUT4
      and HvSUT2 to the vacuole membrane suggests that SUTs also function in vacuolar
      sucrose transport. The transport mechanism of type III SUTs has not been analyzed
      in detail. LjSUT4, a type III sucrose transporter homolog from Lotus japonicus,
      is expressed in nodules and its transport activity has not been previously
      investigated. In this report, LjSUT4 was expressed in Xenopus oocytes and its
      transport activity assayed by two-electrode voltage clamping. LjSUT4 transported
      a range of glucosides including sucrose, salicin, helicin, maltose, sucralose and
      both alpha- and beta-linked synthetic phenyl glucosides. In contrast to other
      sucrose transporters, LjSUT4 did not transport the plant glucosides arbutin,
      fraxin and esculin. LjSUT4 showed a low affinity for sucrose (K(0.5)=16 mM at pH
      5.3). In addition to inward currents induced by sucrose, other evidence also
      indicated that LjSUT4 is a proton-coupled symporter: (14)C-sucrose uptake into
      LjSUT4-expressing oocytes was inhibited by CCCP and sucrose induced membrane
      depolarization in LjSUT4-expressing oocytes. A GFP-fusion of LjSUT4 localized to
      the vacuole membrane in Arabidopsis thaliana and in the roots and nodules of
      Medicago truncatula. Based on these results we propose that LjSUT4 functions in
      the proton-coupled uptake of sucrose and possibly other glucosides into the
      cytoplasm from the vacuole.

PMID- 18618273
TI  - Reduction of urinary tract infections acquired in an intensive care unit during a
      10-year surveillance program.
AB  - PURPOSE: To describe trends of urinary catheter-related infections (UCRIs)
      acquired by patients hospitalized in intensive care units (ICU) in relation with
      an infection control program. MATERIALS AND METHODS: Prospective surveillance in
      one ICU of a university hospital in Lyon (France) between 1995 and 2004. RESULTS:
      A 66% reduction of urinary catheter-related infections (UCRIs) acquired by
      patients hospitalized was observed between 1995 and 2004 after adjustment on age,
      gender, antibiotic use at admission, and duration of exposure to urinary
      catheter. CONCLUSIONS: These results, obtained by continuous epidemiological
      monitoring of nosocomial infections, are encouraging with regard to the
      improvement of infection control measures and the evolution of medical practices.
      Further studies in ICUs are needed to confirm this trend.

PMID- 18618274
TI  - Arsenic trioxide and lead acetate induce apoptosis in adult rat hepatic stem
      cells.
AB  - In the present study, the toxicity of arsenic trioxide and lead acetate was
      assessed in adult hepatic stem cells induced in the 2-acetyl
      aminofluorene/partial hepatectomy rat model. Isolated oval cells were incubated
      separately for 6 h with 40 muM each of arsenic trioxide and lead acetate. 3-(4,5
      Dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay denoted significant
      time-dependent cell death in arsenic and lead treated oval cells. The degree of
      stress imposed by these metals was evidenced by induction of heat shock protein
      (HSP) 70 and HSP 90. Arsenic and lead were found to trigger apoptosis as revealed
      by DNA ladder formation, Western blots of apoptotic factors, and reverse
      transcriptase polymerase chain reaction analyses of bax and bcl-2. Results
      clearly indicate that both arsenic and lead induced apoptosis is caspase-mediated
      and accompanied by extracellular signal-regulated kinase (ERK) dephosphorylation.
      Full-length BH3-interacting-domain death agonist expression in presence of
      caspase 3 inhibitor unravels a direct involvement of caspase in As and Pb induced
      apoptosis. Expression patterns of apoptosis inducing factor, B cell lymphoma-2
      (Bcl-2) antagonist of cell death, Bcl-2-associated X protein, and Bcl2 also
      signify mitochondrial regulation of apoptosis effected by lead and arsenic. It is
      concluded that stimulation of caspase cascade and simultaneous ERK
      dephosphorylation are the most significant operative pathways directly associated
      with apoptotic signals triggered by arsenic and lead in the oval cells.

PMID- 18618275
TI  - Evaluation of antigenotoxicity effects of umbelliprenin on human peripheral
      lymphocytes exposed to oxidative stress.
AB  - The protective properties of a prenylated coumarin, umbelliprenin (UMB), on the
      human lymphocytes DNA lesions were tested. Lymphocytes were isolated from blood
      samples taken from healthy volunteers. DNA breaks and resistance to H(2)O(2)
      induced damage were measured using a single-cell microgel electrophoresis
      technique under alkaline conditions (comet assay). Human lymphocytes were
      incubated in UMB (10, 25, 50, 100, 200, and 400 microM) alone or a combination of
      different concentrations of UMB (10, 25, 50, 100, 200, and 400 microM) and 25
      microM H(2)O(2). Untreated cells, ascorbic acid (AA; 25, 50, 100, 200, and 400
      microM) and H(2)O(2) (25 microM) were considered as negative control, positive
      control, and the standard antioxidant agent for our study, respectively. Single
      cells were analyzed with "TriTek Cometscore version 1.5" software. The DNA damage
      was expressed as percent tail DNA. UMB exhibited a concentration-dependent
      increase in protection activity against DNA damage induced by 25 microM H(2)O(2)
      (from 67.28% to 39.17%). The antigenotoxic activity of AA, in the range 0-50
      microM, was greater than that of UMB. However, no significant difference (p >
      0.05) in the protective activity was found between UMB and AA at concentrations
      of approximately higher than 50 microM.

PMID- 18618276
TI  - Dietary carbohydrate, glycemic index, and glycemic load in relation to colorectal
      cancer risk in the Women's Health Initiative.
AB  - Evidence implicating hyperinsulinemia and insulin resistance in the etiology of
      colorectal cancer suggests that a diet characterized by a high glycemic index and
      load may increase the risk of this disease, but previous studies have yielded
      inconsistent results. We assessed the association between intake of total
      carbohydrates, sugars, fiber, and the glycemic index (GI) and glycemic load (GL)
      of individual diets, and risk of developing colorectal cancer among 158,800
      participants in the Women's Health Initiative (WHI). We used a GI/GL database
      developed specifically for the WHI food-frequency questionnaire. Over an average
      of 7.8 years of follow-up, 1,476 incident cases of colorectal cancer were
      identified. Cox proportional hazards models were used to estimate the association
      between dietary factors classified by quintiles and risk of colorectal cancer,
      with adjustment for covariates. Total carbohydrate intake, glycemic index,
      glycemic load, and intake of sugars and fiber showed no association with
      colorectal cancer. Analyses by cancer subsite also yielded null results, with the
      exception of a borderline positive association between glycemic load and rectal
      cancer (HR for the highest versus lowest quintile 1.84, 95% confidence interval
      0.95-3.56, p for trend 0.05). Analyses stratified by tertiles of body mass index
      and physical activity showed no evidence of effect modification by these factors.
      Results of this large study do not support of a role of a diet characterized by
      high glycemic index or load in colorectal carcinogenesis in postmenopausal women.

PMID- 18618277
TI  - Childhood hematopoietic malignancies and parental use of tobacco and alcohol: the
      ESCALE study (SFCE).
AB  - OBJECTIVES: Investigating the role of parental smoking and maternal alcohol
      consumption in the etiology of childhood hematopoietic malignancies. METHODS: The
      national registry-based case-control study ESCALE was carried out in France over
      the period 2003-2004. Population controls were frequency matched with the cases
      on age and gender. Maternal smoking and alcohol consumption during pregnancy and
      paternal smoking since before conception were reported by the mothers in a
      structured telephone questionnaire. Odds ratios (OR) were estimated using
      unconditional regression models closely adjusted for potential confounders.
      RESULTS: A total of 765 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma
      (HL), 165 of non-Hodgkin's lymphoma (NHL) and 1681 controls were included.
      Paternal smoking was significantly associated with childhood ALL (OR = 1.4 [1.1
      1.7]), AML (OR = 1.5 [1.0-2.3]), Burkitt (OR = 2.0 [1.2-3.2]), and anaplastic
      large cell (OR = 3.2 [1.2-9.1]) NHL. For the four diseases, the ORs significantly
      increased with the number of cigarettes smoked. No association with HL or with
      other types of NHL was observed. The associations with maternal alcohol
      consumption and cigarette smoking during pregnancy were less consistent.
      CONCLUSION: The results support the hypothesis that only paternal smoking, and
      not maternal alcohol consumption or cigarette smoking, plays a role in childhood
      hematopoietic malignancies.

PMID- 18618279
TI  - Changing incidence of AIDS-related Kaposi sarcoma and non-Hodgkin lymphoma in
      Ontario, Canada.
AB  - OBJECTIVE: To examine the influence of the AIDS epidemic on the incidence of
      Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) in Ontario. METHODS: Age
      standardized incidence rates for KS and NHL from 1981 to 2000 were calculated
      from the population-based Ontario Cancer Registry. AIDS cases were extracted from
      Ontario Ministry of Health and Long-Term Care reports. HIV death data were
      obtained from the Ontario Cancer Registry. RESULTS: KS was a rare cancer before
      the 1980s; however, incidence increased sharply between 1985 and 1995 by 13.8%
      per year. Thereafter, incidence rates fell close to those in the early 1980s. NHL
      incidence in males increased steadily during the 1980s at 3.2% per year and then
      slowed beyond 1990. In males aged 30-44, NHL incidence rose from 1981 to 1990
      (8.8% per year) and then fell (-2.5%) thereafter. NHL and KS cases represented
      one-third of HIV deaths. CONCLUSIONS: The AIDS epidemic, the introduction of
      antiretroviral therapies, and the decrease in HIV infection rates explain the
      rise and decline of KS incidence in Ontario. NHL incidence trends are more
      complex, although the AIDS epidemic explains the trends observed in younger men
      (in whom AIDS is more common), and for the AIDS-related subtypes.

PMID- 18618278
TI  - Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and
      Ovarian Cancer Screening Trial.
AB  - OBJECTIVE: A history of diabetes has been fairly consistently related to a
      reduced prostate cancer risk, but previous investigations have not always
      addressed whether the relation with diabetes varies by prostate cancer
      aggressiveness or the association between diabetes and prostate cancer is
      modified by physical activity level and body mass, variables closely related to
      glucose metabolism. METHODS: We prospectively examined the diabetes-prostate
      cancer risk relationship among 33,088 men in the screening arm of the Prostate,
      Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. RESULTS: During 8.9
      years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes
      history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI
      = 0.68-0.95). The apparent protection afforded by diabetes was primarily due to
      the inverse relation with non-aggressive disease (i.e., the combination of low
      grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI
      = 0.62-0.91). In contrast, no association was noted between diabetes and
      aggressive disease (i.e., high grade or high stage (Gleason sum >or=8 or clinical
      stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the
      association between diabetes and aggressive prostate cancer was suggestively
      positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2))
      and it was positive for men who were the most physically active (RR = 1.63; 95%
      CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of
      diabetes to aggressive prostate cancer were noted for their heavier or physically
      less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI
      and physical activity, respectively). CONCLUSION: In this study, diabetes showed
      divergent relations with prostate cancer by tumor aggressiveness. Specifically,
      diabetes was inversely associated with early stage prostate cancer but it showed
      no relation with aggressive prostate cancer. Exploratory analyses suggested a
      positive association between diabetes and aggressive prostate cancer in the
      subgroup of men with a low BMI.

PMID- 18618280
TI  - Anthropometric factors at age 20 years and risk of thyroid cancer.
AB  - Effect of anthropometric factors at adolescence and the change since young age on
      thyroid cancer risk is unclear. Here, we conducted a case-control study to
      investigate the association between anthropometric factors at the time of
      diagnosis and age 20 years and risk of thyroid cancer. A total of 173 patients
      with thyroid cancer (papillary carcinoma, n = 167 and follicular carcinoma, n =
      6) and 865 age- and sex-matched controls were included. Anthropometric factors
      were assessed using a validated self-administered questionnaire and categorized
      into three groups. Odd ratios (ORs) with 95% confidence intervals (CIs) were
      estimated using conditional logistic models adjusted for potential confounders.
      Results showed a positive association between current weights, weight at age 20
      years and height, and thyroid cancer risk. Adjusted ORs in the top tertiles were
      2.46 (95% CI, 1.54-3.94; trend p ? 0.001) for current weight, 2.69 (95% CI, 1.71
      4.25; trend p ? 0.001) for weight at age 20 years and 2.44 (95% CI, 1.52-3.93;
      trend p ? 0.001) for height compared with the lowest tertile. A positive
      association with current body surface area (BSA), BSA at age 20 years, and
      current body mass index was also observed, with respective adjusted ORs in the
      top tertile of 1.96 (95% CI, 1.23-3.11; trend p = 0.007), 1.82 (95% CI, 1.15
      2.88; trend p = 0.007) and 1.71 (95% CI, 1.06-2.78; trend p = 0.034). In
      contrast, no association with risk was seen for a change in anthropometric
      factors since age 20 years. These findings suggested that body size in early life
      as well as in adult is associated with an increased risk of thyroid cancer.

PMID- 18618281
TI  - Abstracting height and weight from medical records, and breast cancer pathologic
      factors.
AB  - Cancer registries routinely collect data on clinicopathologic factors, but rarely
      abstract anthropometric variables. We conducted a chart review study, examining
      the feasibility of abstracting weight, height, alcohol use, and smoking from
      medical records in women (n = 1,974) diagnosed with invasive breast cancer, and
      investigated the association between the abstracted variables with
      clinicopathologic features. Qualitative data were reviewed and categorized.
      Frequencies of the abstracted data, and demographic and clinicopathologic
      variables were calculated. Logistic regression models measured the relationship
      between the outcome variables, tumor size, stage of disease, and
      estrogen/progesterone (ER/PR) status with the abstracted variables. Data on
      current alcohol-use/no-use, current-smoker/non-smoker, and height/weight data
      were obtained on 96%, 97%, and 88-89% of the participants, respectively. The
      multivariate analysis showed that overweight (>or=25 kg/m(2)) women had
      significantly larger (>or=2 cm) tumor size compared with normal weight for both
      women <50 years (OR = 1.79; 95% CI = 1.14-2.81; p <or= 0.05) and for women >or=50
      years at diagnosis (OR = 1.58; 95% CI = 1.19-2.09; p <or= 0.05). These results
      suggest that abstracting current height and weight via medical records is
      feasible, and at minimum, current alcohol use and smoking status can be
      ascertained. In addition, being overweight was significantly associated with
      cancer clinicopathologic/prognostic factors, which has implications for
      monitoring etiologic factors that could be associated with cancer trends,
      incidence, and survival. Therefore routine collection of height and weight via
      cancer registries should be explored further.

PMID- 18618282
TI  - Variability of total and available copper concentrations in relation to land use
      and soil properties in Yangtze River Delta of China.
AB  - The effects of land use and soil properties on total and available Cu
      concentrations in soils were investigated in this study. A total of 276 surface
      (0-20 cm) soil samples were collected from seven land uses: industrial area,
      woodland, vegetable field, dry land, paddy field, tea garden and orchard. The
      total and available (DTPA extractable) Cu concentrations, pH, organic matter, and
      total nitrogen contents, and cation exchange capacity were measured for each
      sample. The correlation and ANOVA analyses showed that land use significantly
      affected total and available Cu concentrations, and the available ratio of soil
      Cu (available Cu concentration/total Cu concentration). On total Cu
      concentration, total nitrogen had significant influence in dry land and paddy
      field, and CEC in garden land; on available Cu concentration, the four measured
      soil properties showed significant influence only in paddy field; on the
      available ratio of Cu, pH had significant effect in paddy field and woodland, and
      CEC in industrial area. Moreover, the relationship between available Cu
      concentration and soil properties was constructed in different land uses. Spatial
      analysis of grain Cu using indicator Kriging showed that most of the study areas
      were in low risk for arable activities, and 7.94% of the study area and 5.10% of
      the arable land were in high risk probability.

PMID- 18618283
TI  - A comprehensive method for aeolian particle granulometry and micromorphology
      analyses.
AB  - The aim of this study was to use a new approach to investigate aeolian particle
      granulometry and micromorphology. Taking total aeolian deposition into account,
      we used parameters such as, particle area, perimeter, shape analysis for particle
      roughness (area/perimeter) and elongation (long/short axis). These parameters
      were analyzed on temporal and spatial scales at four study sites in the eastern
      Negev Desert, Israel. The total collection of particles was sorted into three
      size groups based on particle area to facilitate comparison. The classic
      definition of particle size (equating particle length with particle diameter)
      produced relatively small variations among the three size classes (25-38.6%). Our
      proposed comprehensive method demonstrated significant variation among the three
      size classes (13.9-60.8%), e.g. the classic method placed 36.4% of the particles
      in size class two while the new method placed 60.8% of the particles in this size
      class; the differences were even more significant regarding size class 3 (38.6%
      vs. 13.9%, respectively). The classic method did not facilitate investigation of
      particle roughness and elongation. With this new approach, it was possible to
      clearly define the particles by size class, based on these characteristics. With
      roughness, the variation among size classes 2 and 3 was about 27%. With
      elongation, the variation among size classes two and three was about 21%.
      Applying similar investigation method to study the aeolian particle granulometry
      and micromorphology can better facilitate more detailed calculation of particle
      size distribution, roughness and elongation.

PMID- 18618284
TI  - N isotopes and N cycle in the TieShanPing subtropical forest ecosystem,
      Southwestern China.
AB  - Nitrogen is essential for forest growth and forest stand development. It is
      commonly a limited factor for forest productivity. We examined delta (15)N values
      in soils and plants by studying the sources of N used by vegetation and cycles of
      N in a 43-year-old plantation of the TieShanPing forest ecosystem in southwestern
      China, dominated by massone pine (Pinus massoniana). The N concentration of plant
      materials ranges from 1.1% to 2.2%. The nitrogen concentration of P. massoniana
      was 1.3% while soils showed the concentration of 0.04-0.15%. Regarding natural
      abundance of (15)N, large significant variation (-6.0 per thousand to -3.8 per
      thousand) in delta (15)N values was observed among shrub and tree leaves. delta
      (15)N values were also significantly varied from -4.7 per thousand to -3.8 per
      thousand among the pioneer species in the plantation. Soil delta (15)N values
      (3.1-6.3 per thousand) were significantly enriched compared to those values in
      plant samples. Despite the negative delta (15)N values of the vegetation cover,
      the high delta (15)N values in the topsoil indicate that return of N to soils by
      litter-fall is minimal on TieShanPing and the present forests do not change very
      much the soil (15)N signals at the surface layer. The positive delta (15)N values
      may also indicate large N losses from the soil system vial leaching,
      volatilization and plant uptake.

PMID- 18618285
TI  - Expression of Dm-AMP1 in rice confers resistance to Magnaporthe oryzae and
      Rhizoctonia solani.
AB  - Magnaporthe oryzae and Rhizoctonia solani, are among the most important pathogens
      of rice, severely limiting its productivity. Dm-AMP1, an antifungal plant
      defensin from Dahlia merckii, was expressed in rice (Oryza sativa L. sp. indica
      cv. Pusa basmati 1) using Agrobacterium tumefaciens-mediated transformation.
      Expression levels of Dm-AMP1 ranged from 0.43% to 0.57% of total soluble protein
      in transgenic plants. It was observed that constitutive expression of Dm-AMP1
      suppresses the growth of M. oryzae and R. solani by 84% and 72%, respectively.
      Transgenic expression of Dm-AMP1 was not accompanied by an induction of
      pathogenesis-related (PR) gene expression, indicating that the expression of
      DmAMP1 directly inhibits the pathogen. The results of in vitro, in planta and
      microscopic analyses suggest that Dm-AMP1 expression has the potential to provide
      broad-spectrum disease resistance in rice.

PMID- 18618286
TI  - Growth, feed efficiency and blood profile of buffalo calves consuming high levels
      of fluoride: growth and blood metabolites in buffaloes fed high fluoride.
AB  - Twelve male buffalo calves of 10 to 12 months of age were divided into 3 groups
      of four each. They were fed wheat straw+concentrate mixture +3 Kg greens. The
      chemical composition of the diet was same in all the three groups except fluoride
      which was added (as NaF) in concentrate mixture of group B and C to make the
      final fluoride concentration 30 ppm and 60 ppm respectively. The animals were
      kept on scheduled diet for a period of 90 days. Body weights were recorded at the
      start of the experiment and at fortnightly interval thereafter. Analysis of data
      revealed that the dry matter intake decreased non significantly in group B and C
      as compared to control group. A significant decrease in serum calcium and a
      significant increase in phosphorus concentration were observed in group C
      animals. A significant increase was observed in alkaline phosphatase activity in
      group C animals. A non significant decrease was observed in T4 values in group C
      animals. On the basis of these results it could be concluded that fluoride in the
      diet of buffalo calves @ 30 ppm is a safe level whereas 60 ppm has affected the
      blood metabolites.

PMID- 18618288
TI  - Neurocognitive testing in late-onset Tay-Sachs disease: a pilot study.
AB  - OBJECTIVES: To test neurocognitive function in patients with late-onset Tay-Sachs
      disease (LOTS) using a computerized system to assess whether cognition is a
      clinically relevant outcome measure of possible therapeutic intervention in LOTS.
      METHODS: Ten adults with Tay-Sachs disease were administered at least one battery
      of the Mindstreams Neurotrax system for evaluation of cognitive function. Six sub
      scores and a Global Cognitive Score (GCS) were tabulated. A disease specific
      severity score was also devised with six domains. RESULTS: Despite identical
      genotypes, all patients but the two oldest had > or = 3/6 sub-scores one standard
      deviation below normal mean (100); verbal and executive functions were most
      affected. The severity score measured other functions. CONCLUSIONS: Because of
      provocative findings on re-testing in patients exposed to miglustat, and despite
      the very small cohort, cognitive function may be an appropriate and clinically
      relevant outcome measure for future therapeutic interventions in LOTS.

PMID- 18618287
TI  - Auxiliary proteins involved in the assembly and sustenance of photosystem II.
AB  - Chloroplast proteins that regulate the biogenesis, performance and acclimation of
      the photosynthetic protein complexes are currently under intense research.
      Dozens, possibly even hundreds, of such proteins in the stroma, thylakoid
      membrane and the lumen assist the biogenesis and constant repair of the water
      splitting photosystem (PS) II complex. During the repair cycle, assistance is
      required at several levels including the degradation of photodamaged D1 protein,
      de novo synthesis, membrane insertion, folding of the nascent protein chains and
      the reassembly of released protein subunits and different co-factors into PSII in
      order to guarantee the maintenance of the PSII function. Here we review the
      present knowledge of the auxiliary proteins, which have been reported to be
      involved in the biogenesis and maintenance of PSII.

PMID- 18618289
TI  - Neurological findings in Hunter disease: pathology and possible therapeutic
      effects reviewed.
AB  - Hunter disease (mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal
      storage disease caused by deficiency of iduronate-2-sulfatase. Accumulation of
      chondroitin sulfate B and heparan sulfate in various tissues is the biochemical
      consequence of MPS II. Children with Hunter disease are normal at birth, and
      symptoms occur between 2 and 10 years of age. Typical symptoms include coarse
      facies with enlarged tongue and prominent forehead as well as a short, stocky
      built stature with short neck. The cardiovascular, respiratory and
      gastrointestinal systems may be affected, and oral, dermatological and
      psychiatric as well as neurological complications are described. Life expectancy
      is markedly reduced and may be limited to 12 years for severely affected
      patients. The most common causes of death are airway obstruction and cardiac
      failure. The most severe symptoms may result from neurological symptoms or
      complications including hydrocephalus, spinal cord compression, cervical
      myelopathy, optic nerve compression, and hearing impairment. Patients may also
      develop carpal tunnel syndrome, sleep apnoea, seizures or mental retardation.
      This review describes characteristic neurological manifestations in MPS II and
      its underlying pathophysiology. In addition, an appraisal is given whether or not
      enzyme replacement therapy may be able to improve in particular the neurological
      symptoms of Hunter disease.

PMID- 18618290
TI  - Ultrasound-mediated microbubble destruction facilitates gene transfection in rat
      C6 glioma cells.
AB  - The goal of this study was to determine whether ultrasound (US) exposure combined
      with microbubble destruction could be used to enhance non-viral gene delivery in
      rat C6 glioma cells. Microbubbles were prepared and gently mixed with plasmid
      DNA. The mixture of the DNA and microbubbles was administered to cultured C6
      cells under different US/microbubble conditions. Transfection efficiency and cell
      viability were assessed by FACS analysis, confocal laser scanning microscopy, and
      Trypan blue staining. The results demonstrate that microbubble with US exposure
      could significantly enhance the reporter gene expression as compared with other
      groups. No statistical significant difference was observed in the glioma cell
      viability between different groups. Our in vitro findings suggest that US
      mediated microbubble destruction has the potential to promote safe and efficient
      gene transfer into C6 cells. This non-invasive gene transfer method may be useful
      for safe clinical gene therapy of brain cancer without a viral vector system.

PMID- 18618291
TI  - Cloning and characterization of the tiger shrimp lysozyme.
AB  - Lysozymes are key proteins to invertebrates in the innate immune responses
      against bacterial infections. A lysozyme gene isolated from tiger shrimp, Penaeus
      monodon, was cloned, sequenced and characterized. The cDNA consists of a signal
      peptide of 18 amino acids and a mature peptide of 140 amino acids. The lysozyme
      is presumed to be a chicken-type lysozyme for it possesses two catalytic sites
      and eight cysteine residues which are highly conserved across species of chicken
      type lysozymes. The lysozyme cDNAs of Penaeus semisulcatus, Litopenaeus vannamei,
      Macrobrachium nipponense and Macrobrachium rosenbergii were also cloned. High
      similarities existed among shrimp and prawn lysozymes but phylogenetic
      relationship of shrimps and prawns based on lysozyme molecules did not quite
      consistent with traditional taxonomic classification. High mRNA expression was
      detected in hepatopancreas, haemocytes and gill of tiger shrimp. Recombinant
      lysozyme exhibited potent lytic activities against fish pathogens providing
      evidence of the involvement of lysozyme in shrimp immunity.

PMID- 18618293
TI  - Banking human tissue for research: vision to reality.
AB  - Advances in scientific understanding of disease together with introduction of new
      high throughput technologies have led to increased demand for human tissue in
      research. In general, patients are willing to donate for research, particularly
      samples that are surplus to diagnostic or therapeutic requirements. New tissue
      specific regulations in the UK are intended to facilitate the use of human tissue
      in research. Despite this positive environment there are challenges to researcher
      access. Coordinated, systematic collection and storage, via a biobank can provide
      easier access. However translating a vision for a biobank into reality whether in
      the public or private sector, has never been simple. But it can be done.

PMID- 18618292
TI  - Quality of life as a prognostic factor of overall survival in patients with
      advanced hepatocellular carcinoma: results from two French clinical trials.
AB  - AIM: The aims of our study were to assess quality of life (QoL) as a prognostic
      factor of overall survival (OS) and to determine whether QoL data improved three
      prognostic classifications among French patients with advanced hepatocellular
      carcinoma (HCC). METHODS: We pooled two randomized clinical trials conducted by
      the Federation Francophone de Cancerologie Digestive in a palliative setting. In
      each trial QoL was assessed at baseline using the Spitzer QoL Index (0-10). Three
      prognostic classifications were calculated: Okuda, Cancer of the Liver Italian
      Program (CLIP), and Barcelona Clinic Liver Cancer group (BCLC) scores. To explore
      whether the scores could be improved by including QoL, univariate Cox analyses of
      all potential baseline predictors were performed. A final multivariate Cox model
      was constructed including only significant multivariate baseline variables likely
      to result in improvement of each scoring system. In order to retain the best
      prognostic variable to add for each score, we compared Akaike information
      criterion, likelihood ratio, and Harrell's C-index. Cox analyses were stratified
      for each trial. RESULTS: Among 538 included patients, QoL at baseline was
      available for 489 patients (90%). Longer median OS was significantly associated
      with higher Spitzer scores at baseline, ranging from 2.17 months (Spitzer=3) to
      8.93 months (Spitzer=10). Variables retained in the multivariate Cox model were:
      jaundice, hepatomegaly, hepatalgia, portal thrombosis, alphafetoprotein,
      bilirubin, albumin, small HCC, and Spitzer QoL Index (hazard ratio=0.84 95% CI
      [0.79-0.90]). According to Harrell's C-index, QoL was the best prognostic
      variable to add. CLIP plus the Spitzer QoL Index had the most discriminating
      value (C=0.71). CONCLUSIONS: Our results suggest that QoL is an independent
      prognostic factor for survival in HCC patients with mainly alcoholic cirrhosis.
      The prognostic value of CLIP score could be improved by adding Spitzer QOL Index
      scores.

PMID- 18618294
TI  - The impact of the International Atomic Energy Agency (IAEA) program on radiation
      and tissue banking in Brazil.
AB  - Until 2000, efforts into organising tissue banks in Brazil had not progressed far
      beyond small "in house" tissue storage repositories, usually annexed to
      Orthopaedic Surgery Services. Despite the professional entrepreneurship of those
      working as part time tissue bankers in such operations, best practices in tissue
      banking were not always followed due to the lack of regulatory standards,
      specialised training, adequate facilities and dedicated personnel. The Skin Bank
      of the Plastic Surgery Department of the Hospital das Clinicas of Sao Paulo, the
      single skin bank in Brazil, was not an exception. Since 1956, restricted and
      unpredictable amounts of skin allografts were stored under refrigeration for
      short periods under very limited quality controls. As in most "tissue banks" at
      that time in Brazil, medical and nursing staff worked on a volunteer and informal
      basis undergoing no specific training. IAEA supported the implementation of the
      tissue banking program in Brazil through the regional project RLA/7/009 "Quality
      system for the production of irradiated sterilised grafts" (1998-2000) and
      through two interregional projects INT/6/049 "Interregional Centre of Excellence
      in Tissue Banking", during the period 2002-2004 and INT/6/052 "Improving the
      Quality of Production and Uses of Radiation Sterilised Tissue Grafts", during the
      period 2002-2004. In 2001-2002, the first two years of operation of the HC-Tissue
      Bank, 53 skin transplants were carried out instead of the previous 4-5 a year.
      During this period, 75 individuals donated skin tissue, generating approximately
      90,000 cm(2) of skin graft. The IAEA program were of great benefit to Brazilian
      tissue banking which has evolved from scattered make shift small operations to a
      well-established, high quality tissue banking scenario.

PMID- 18618295
TI  - Collective informed consent and decision power.
AB  - It has been suggested that, in addition to individual level decision-making,
      informed consent procedures could be used in collective decision-making too. One
      of the main criticisms directed at this suggestion concerns decision-making
      power. It is maintained that consent is a veto power concept and that, as such,
      it is not appropriate for collective decision-making. This paper examines this
      objection to collective informed consent. It argues that veto power informed
      consent can have some uses in the collective level and that when it is not
      appropriate the decision power a concerned party ought to have in connection with
      an arrangement should be made relative to the interest she has at stake in it. It
      concludes that the objection examined does not undermine collective informed
      consent.

PMID- 18618296
TI  - Correlation of enteric NADPH-d positive cell counts with the duration of
      incubation period in NADPH-d histochemistry.
AB  - Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining can be
      used in the enteric nervous system to determine nitrergic neuronal counts,
      critical in motility disorders such as intestinal neuronal dysplasia and
      hypoganglionosis. The reported incubation periods of specimens with NADPH-d
      staining solution has varied from 2 to 24 h. The aim of this study is to
      investigate the impact of the incubation period on the overall NADPH-d positive
      cell counts in porcine rectal submucosal plexus. The submucosal plexus of rectal
      specimens from 12-week-old pigs (n = 5) were studied. Conventional frozen
      sections were used to identify nitrergic neurons while whole-mount preparations
      were used to quantify the effect of prolonged duration of incubation on
      positively identified ganglion cells with NADPH-d histochemistry. The same
      submucosal ganglia on the conventional sections, and a minimum of 12 ganglia per
      whole-mount preparation specimen were photographed sequentially at 2, 6, and 24 h
      and used to count the number of nitrergic cells per ganglion. The same staining
      solution was used throughout the experiment. Results were analysed using a one
      way ANOVA test. Prolonged incubation with the staining solution revealed new
      NADPH-d positive cells in the ganglia on the conventional sections. The total
      number of neurons counted in the 12 adjacent ganglia in the whole-mount specimens
      was 180 +/- 55, the mean neuronal cell per ganglion was 15 +/- 8 after 2 h of
      incubation. This increased to 357 +/- 17, and to 29 +/- 12 after 6 h (p < 0.05).
      A further increase was observed of 515 +/- 19 and 43 +/- 17 after 24 h (p <
      0.05). When the photomicrographs were retrospectively analysed, not even the
      outline of the neuronal cells that stained with prolonged incubation was evident
      at the earlier time points. NADPH-d positive cell counts increase in proportion
      to the duration of incubation in NADPH-d histochemistry. Comparative studies
      attempting to quantify nitrergic cell counts in dysmotility disorders must take
      into account the variability in NADPH-d positive cell count associated with
      prolonged incubation in NADPH-d histochemistry.

PMID- 18618297
TI  - Expression of cholera toxin B subunit in transgenic rice endosperm.
AB  - The synthetic cholera toxin B subunit (CTB) gene, modified according to the
      optimized codon usage of plant genes, was introduced into a plant expression
      vector and expressed under the control of the Bx17 HMW (high molecular weight)
      wheat endosperm-specific promoter containing an intron of the rice act1. The
      recombinant vector was transformed into rice plants using a biolistic-mediated
      transformation method. Stable integration of the synthetic CTB gene into the
      chromosomal DNA was confirmed by PCR amplification analysis. A high level of CTB
      (2.1% of total soluble protein) was expressed in the endosperm tissue of the
      transgenic rice plants. The synthetic CTB produced only in the rice endosperm
      demonstrated strong affinity for G(M1)-ganglioside, thereby suggesting that the
      CTB subunits formed an active pentamer. The successful expression of CTB genes in
      transgenic plants makes it a powerful tool for the development of a plant-derived
      edible vaccine.

PMID- 18618299
TI  - Dynamic contrast enhanced magnetic resonance imaging of bladder cancer and
      implications for biological image-adapted radiotherapy.
AB  - PURPOSE: To assess the role of image parameters derived from dynamic contrast
      enhanced magnetic resonance imaging (DCEMRI) in bladder cancer staging, and to
      investigate the potential use of such parameter images in biological image
      adapted radiotherapy (RT). MATERIALS AND METHODS: High-resolution volumetric
      interpolated breath-hold (VIBE) DCEMRI of 26 patients diagnosed with bladder
      cancer was performed. DCEMRI parameters derived from tumor and muscle contrast
      uptake curves were extracted and subjected to correlation analysis with tumor
      volume as well as clinical, pathological, histological and T2-weighted MR tumor
      stage. For parameters showing a significant correlation with tumor stage, 3D
      malignancy maps were generated. As an initial step towards delivery of
      biologically adapted intensity modulated radiotherapy (IMRT) it was hypothesized
      that the malignancy map could be used as a RT dose prescription map. Simulating
      IMRT delivery with multi-leaf collimators (MLCs), idealized dose distributions,
      constituted by dose cubes, were adapted to the prescription map. The size of the
      dose cubes were varied to mimic MLCs of varying leaf width. The difference
      between the adapted and prescribed dose distributions was quantified by the root
      mean square deviation (RMSD). RESULTS: No significant relationships were found
      between tumor volume and extracted DCEMRI parameters. The normalized area between
      tumor and muscle contrast uptake curves (nABC) evaluated from 0-180 seconds
      (nABC(180)) and 0-480 s (nABC(480)) correlated significantly with tumor stage
      (p=0.047 and p=0.035, respectively). Dose prescription maps for 10 patients were
      generated from the nABC(480). The RMSD between the prescribed and adapted dose
      distribution decreased with decreasing size of the dose cubes. Large interpatient
      variations in the RMSD and in the dependence of the RMSD on different dose cube
      sizes were found. CONCLUSIONS: The nABC(180) and nABC(480) may provide added
      value in staging of bladder cancer. High-resolution IMRT is required for some
      patients for optimal adapted RT.

PMID- 18618298
TI  - Broadening the scope of image-guided radiotherapy (IGRT).
AB  - The recent wave of enthusiasm for image guidance in radiation therapy is largely
      due to the advent of on-line imaging devices. The current narrow definition of
      image-guided radiotherapy (IGRT), in fact, essentially connotes the use of near
      real-time imaging during treatment delivery to reduce uncertainties in target
      position and should therefore be termed IGRT-D. However, a broader (and more
      appropriate) context of image-guidance should include: (1) detection and
      diagnosis, (2) delineation of target and organs at risk, (3) determining
      biological attributes, (4) dose distribution design, (5) dose delivery assurance
      and (6) deciphering treatment response through imaging i.e. the 6 D's of IGRT.
      Strategies to advance these areas will be discussed.

PMID- 18618300
TI  - Inverse correlation of aberrant expression of fragile histidine triad (FHIT)
      protein with cyclin D1 protein and prognosis in Chinese patients with
      cholangiocarcinoma.
AB  - BACKGROUND: This is the first study to explore the relationship between the
      expression of fragile histidine triad, FHIT and cyclin D1 proteins, and the
      clinicopathological significance of the two proteins in Chinese patients with
      cholangiocarcinoma. MATERIAL AND METHODS: Immunohistochemistry was used to study
      53 cases of cholangiocarcinoma, 30 para-neoplastic and 20 normal bile ducts for
      their expression status of FHIT and cyclin D1 and then the results were analyzed
      with the patient's age, sex, tumour site, histological grade and clinical stage
      as well as overall median survival time. RESULTS: Compared with the para
      neoplastic and normal cholangiocytes, the expression of FHIT was obviously
      decreased (p=0.0001), whereas that of cyclin D1 was significantly increased
      (p=0.0001) in carcinoma cells. The expression of FHIT was found to be correlated
      with the histological grade (p=0.007) and the clinical stage (p=0.004), but not
      with age (p=0.776), sex (p=0.246) or tumour site (p=0.347). The expression of
      cyclin D1 was also showed statistically associated with the histological grade
      (p=0.043) and clinical stage (p=0.047), but not with age (p=0.965), sex (p=0.751)
      or tumour site (p=0.948). Further, the expression of FHIT was found to be
      inversely correlated with the expression of cyclin D1 (p=0.0001). The loss of
      expression of FHIT and the expression of cyclin D1 were significantly related to
      the cancers with shorter median survival time (p=0.0001, p=0.0081). The
      expression of FHIT was an independent prognostic factor (p=0.005). DISCUSSION:
      The expression of FHIT may be inversely correlated with the expression of cyclin
      D1. It is suggested that the loss of FHIT protein and overexpression of cyclin D1
      protein may play an important role in carcinogenesis and prognosis of
      cholangiocarcinoma.

PMID- 18618301
TI  - Fluoroscopy-guided percutaneous lung biopsy: a valuable alternative to computed
      tomography.
AB  - BACKGROUND: Computed tomography (CT) fluoroscopy nowadays is the most preferred
      method of guidance to perform percutaneous lung biopsy of pulmonary masses.
      Conventional fluoroscopy is an increasingly forgotten technique that still can be
      used to perform lung biopsies, with many advantages. PURPOSE: To compare the
      accuracy, safety, and effective dose (ED) of conventional fluoroscopy-guided
      needle lung biopsy (FNLB) with CT-guided needle lung biopsy procedures (CTNLB)
      reported in the literature. MATERIAL AND METHODS: 100 consecutive patients who
      underwent FNLB were reviewed retrospectively. Using the final histological
      diagnoses and the clinical and radiological course of the disease as references,
      the accuracy and sensitivity of FNLB were calculated. The complication rates of
      FNLB were assessed. Using computer software (XDOSE), the ED was calculated. The
      accuracy, complication rates, and the ED of FNLB were compared with CTNLB
      reported in the literature. RESULTS: The overall accuracy rate and sensitivity of
      FNLB were both 87%, which are comparable to the range of accuracies reported in
      the literature for CTNLB (74-97%). The complication rates of FNLB were also
      comparable to the complication rates reported for CTNLB. The commonest
      complication was pneumothorax, at a rate of 25%. The ED of FNLB was small,
      significantly lower than reported in the literature for CT-guided procedures. The
      mean ED of FNLB was 0.029 mSv, which is approximately equivalent to one chest X
      ray. CONCLUSION: Conventional fluoroscopy is an accurate, safe, and low-dose
      alternative modality to CT to obtain an image-guided histological diagnosis of
      pulmonary lesions.

PMID- 18618302
TI  - Large-core needle biopsy versus fine-needle aspiration biopsy in solid breast
      lesions: comparison of costs and diagnostic value.
AB  - BACKGROUND: In the current climate of budget constraints and personnel shortages,
      hospitals are required to demonstrate ever-greater cost effectiveness. In the
      diagnosis of breast lesions, it is useful to compare the costs and benefits of
      fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB). PURPOSE: To
      determine the total costs of FNAB and CNB of breast lesions, and to compare the
      costs and diagnostic value of these methods. MATERIAL AND METHODS: The material
      consisted of 688 breast lesion cases from a Finnish breast-imaging unit. All
      cases underwent FNAB and/or CNB. Based on the primary biopsy method used, the
      cases were allocated to the FNAB (n=590) or CNB (n=98) group. Data on costs,
      sensitivity, and specificity were used to compare the cost effectiveness of the
      two methods. RESULTS: 590 FNABs were performed in the FNAB group and 98 CNBs in
      the CNB group. In addition, we needed 78 CNBs in the FNAB group and 11 FNABs in
      the CNB group for further assessment. The false-negative rate for FNAB was 19%
      and for CNB 11%; the false-positive rates were 9% and 1%, respectively. The
      average cost of biopsies per case in the FNAB group was euro 66 and in the CNB
      group euro 221. FNAB was most expensive when performed under ultrasound guidance
      (euro 44.65) and CNB when performed under stereotactic guidance (euro 246.37).
      CONCLUSION: FNAB is a less reliable and less informative diagnostic method than
      CNB. Although a negative or indeterminate FNAB result requires follow-up or a re
      biopsy with core needle, it is still a cost-effective procedure. Stereotactic
      guidance considerably increases the costs of CNB, and therefore US guidance
      should be used whenever possible.

PMID- 18618303
TI  - A common haplotype within the PON1 promoter region is associated with sporadic
      ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder
      of upper and lower motor neurons. Genetic variants in the paraoxonase gene
      cluster have been associated with susceptibility to sporadic ALS. Because these
      studies have yielded conflicting results, we have further investigated this
      association in a larger data set. Twenty SNPs spanning the paraoxonase gene
      cluster were genotyped on a panel of 597 case and 692 control samples and tested
      for association with risk of sporadic ALS and with ALS sub-phenotypes. Our study
      revealed two SNPs, rs987539 and rs2074351, within the paraoxonase gene cluster
      that are associated with susceptibility to sporadic ALS (uncorrected p=6.47E-04
      and 7.87E-04, respectively). None of the 20 SNPs displayed significant
      associations with age of onset, site of onset or disease survival. Using a
      sliding window approach, we have also identified a 5-SNP haplotype that is
      significantly associated with risk of sporadic ALS (p=2.75E-05). We conclude that
      a common haplotype within the PON1 promoter region is associated with
      susceptibility to sporadic ALS.

PMID- 18618305
TI  - Influence of alcohol on the release of tramadol from 24-h controlled-release
      formulations during in vitro dissolution experiments.
AB  - Recent warnings by regulatory bodies and a product recall by the FDA have
      generated much interest in the area of dose dumping from controlled-release
      opioid analgesic formulations when coingested with alcohol. It was the aim of
      this study to address this issue and in doing so, gain understanding on how
      alcohol-induced effects may be avoided. In this study, tramadol release from
      Ultram ER tablets and T-long capsules was significantly increased in the presence
      of ethanol. Conversely, a decrease in the rate of tramadol release was seen from
      Tridural extended-release tablets in the presence of alcohol.

PMID- 18618304
TI  - Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic
      lateral sclerosis mice.
AB  - Recent evidence suggests that transcriptional dysregulation may play a role in
      the pathogenesis of amyotrophic lateral sclerosis (ALS). The histone deacetylase
      inhibitor, sodium phenylbutyrate (NaPB), is neuroprotective and corrects aberrant
      gene transcription in ALS mice and has recently been shown to be safe and
      tolerable in ALS patients while improving hypoacetylation. Since many patients
      are already on riluzole, it is important to ensure that any proposed therapy does
      not result in negative synergy with riluzole. The combined treatment of riluzole
      and NaPB significantly extended survival and improved both the clinical and
      neuropathological phenotypes in G93A transgenic ALS mice beyond either agent
      alone. Combination therapy increased survival by 21.5%, compared to the separate
      administration of riluzole (7.5%) and NaPB (12.8%), while improving both body
      weight loss and grip strength. The data show that the combined treatment was
      synergistic. In addition, riluzole/NaPB treatment ameliorated gross lumbar and
      ventral horn atrophy, attenuated lumbar ventral horn neuronal cell death, and
      decreased reactive astrogliosis. Riluzole/NaPB administration increased
      acetylation at H4 and increased NF-kappaB p50 translocation to the nucleus in
      G93A mice, consistent with a therapeutic effect. These data suggest that NaPB may
      not interfere with the pharmacologic action of riluzole in ALS patients.

PMID- 18618306
TI  - Bioadhesive ranitidine hydrochloride for gastroretention with controlled
      microenvironmental pH.
AB  - Ranitidine hydrochloride is a H(2) receptor blocker used in the treatment of
      gastric ulcers. Pharmacological factors, in addition to the dosage regimen, favor
      development of a sustained-release system for ranitidine especially in the
      therapeutic condition of erosive esophagitis. This investigation delves into the
      development of bioadhesive type of gastroretentive formulation (tablets) of
      ranitidine. The effect of mucoadhesive polymers such as Carbopol, hydroxypropyl
      methyl cellulose, and dextrose were studied. Mucoadhesion, in vitro drug release
      profile, water uptake, and swelling of the tablet were evaluated. Alkalizing
      agents were incorporated in an attempt to maintain an alkaline microenvironment
      within the tablet and improve the stability of the drug in acidic medium. The
      stability was evaluated using dye test and degradation studies. The drug release
      profiles were fit into various kinetic models.

PMID- 18618307
TI  - Validation of a simple and rapid HPLC method for determination of metronidazole
      in dermatological formulations.
AB  - A rapid and simple method using an isocratic high-pressure liquid chromatography
      (HPLC) and UV detection for the determination of metronidazole in dermatological
      formulations is presented. Metronidazole samples were extracted with a solution
      composed of 60% methanol and 40% mobile phase by a procedure that can be
      completed in less than 10 min. Subsequent separation and quantification was
      accomplished in less than 20 min using reversed-phase HPLC with isocratic elution
      with 0.01% trifluoroacetic acid/acetonitrile (85:15%, vol/vol). Validation
      experiments confirmed the precision and accuracy of the method. When applied to a
      commercial metronidazole cream and gel formulation, recoveries of 100.4% for
      cream formulations and 102.3% for gel formulations were obtained. The method
      should facilitate studies of the formulation compatibility of metronidazole
      topical formulations with agents that may improve its clinical tolerability for
      treatment of rosacea.

PMID- 18618308
TI  - In vitro permeation characterization of the analgesic ibuprofen and the sunscreen
      oxybenzone.
AB  - Ibuprofen, one of the mostly prescribed nonsteroidal anti-inflammatory drugs
      (NSAIDs), has been proposed as a topical medication for secondary prevention
      against skin damage induced by sunburn. The objective of this study was to
      characterize transmembrane permeation of ibuprofen and sunscreen oxybenzone
      across poly(dimethyl siloxane) (PDMS) membrane. In vitro diffusion studies were
      carried out at 37 degrees and 45 degrees C, using a series of ibuprofen and
      oxybenzone samples, either individually or in combination. Concentrations of
      ibuprofen and oxybenzone in the receptor compartment for up to 6 h were measured
      using a high-performance liquid chromatography (HPLC) assay. Ibuprofen and
      oxybenzone permeated across the PDMS membrane in all diffusion studies. When
      applied individually, permeation percentages of ibuprofen and oxybenzone ranged
      from 1.0 to 4.1% and from 13.2 to 25.8%, respectively. When applied in
      combination, permeation percentages of ibuprofen and oxybenzone were 0.3-1.4% and
      7.8-24.3%, respectively. Transmembrane permeation was significantly suppressed
      when both compounds were present concurrently. High temperature promoted the
      diffusion process of oxybenzone; a linear correlation was also observed between
      oxybenzone concentration and its permeation. The proposed permeation enhancement
      between ibuprofen and oxybenzone was not observed from this study. The potential
      transdermal interaction and systemic absorption from concurrent application of
      topical analgesics and sunscreens thus requires further systematic evaluation.

PMID- 18618309
TI  - Pellet starters in layering technique using concentrated drug solution.
AB  - Characteristics of inert starters in drug solution layering are important for
      successful active pellet formation. Four types of starters composed of sucrose or
      microcrystalline cellulose (MCC) or lactose and MCC were compared in our study.
      The active pellets were prepared using Wurster type apparatus. Yield and pellet
      quality parameters were determined. The highest yield (85.66-89.41%) was obtained
      for cores composed of MCC due to their insolubility in water (the drug solvent)
      and good mechanical properties. On the contrary, soluble and brittle sucrose
      cores dissolved partially during the process forming undesirable agglomerates and
      giving lower yield (76.2%). All pellet samples showed good flow properties and
      drug content from 82.4 to 94.5% of the theoretical drug amount.

PMID- 18618310
TI  - Evaluation and floating enhancement of levodopa sustained release floating
      minitablets coated with insoluble acrylic polymer.
AB  - This article describes the in vitro evaluation and the enhancement of the
      floating properties of coated sustained release (SR) minitablets (MTs). The
      evaluated system consisted of a 3-mm drug-containing gas-generating core prepared
      by melt granulation and subsequent compression, which was then coated with a
      flexible polymeric membrane. Eudragit RL30D and acetyl triethylcitrate were used
      as a film former and a plasticizer, respectively. The coating level was fixed at
      20% (wt/wt). The optimally coated floating MTs floated within 10 min and remained
      buoyant for more than 13 h, regardless of the pH of the test medium. By
      evaluating the dissolution profiles of levodopa at different pH, it was found
      that the release of levodopa was sustained for more than 12 h regardless of the
      pH, even if the coating did not cancel the effect of the pH-dependent solubility
      of the active drug. Finally, the robustness of the coated floating MTs was
      assessed by testing the drug release variability in function of the stirring
      conditions during dissolution tests.

PMID- 18618311
TI  - Pretreatment of mice with rifampicin prolongs survival of endotoxic shock by
      modulating the levels of inflammatory cytokines.
AB  - To investigate the effects of rifampicin in a mouse model of endotoxin shock,
      mice were pretreated with rifampicin for at different times before and after
      challenging with a lethal dose of lipopolysaccharide (LPS). We found that
      rifampicin had a significant preventive effect and reduced the mortality of mice
      at early stages. To further understand the mechanism, plasma cytokine levels were
      examined. Mice treated with LPS alone showed markedly increased plasma levels of
      TNF, IL-1beta, IL-6, and IL-10, while mice pretreated with rifampicin showed
      significantly lower plasma levels of these cytokines compared to the LPS alone.
      Our results suggest that rifampicin has a beneficial effect on septic shock
      caused by LPS through modulation of cytokines. This suggests that rifampicin
      could be a candidate for treatment of septicemia caused by gram-negative
      bacterial infection.

PMID- 18618312
TI  - Echinacea-induced macrophage activation.
AB  - Public interest in Echinacea is growing rapidly. Unfortunately, there is little
      scientific evidence to support claims of efficacy of this widely used botanical,
      and little information about potential mechanism of action. This study examines
      the ability of Echinacea to upregulate macrophage function and begins to
      elucidate the mechanism of Echinacea-induced macrophage activation. Murine
      peritoneal macrophages were cultured with E. purpurea extracts enriched for plant
      polysaccharide (EP). ELISA was used to measure cytokine production. MAPKs were
      blocked using specific inhibitors, and Western blotting used to identify
      phosphorylated proteins involved in signal transduction. To examine in vivo
      efficacy, EP was administered orally and Listeria monocytogenes given i.v. Mice
      were sacrificed three days post-infection to determine bacterial load in the
      spleen. We demonstrate that an endotoxin-free EP extract activates the innate
      immune response, stimulating production of IL-6, TNF, IL-12, and NO from
      macrophages in vitro. Along with evidence of enhanced macrophage function, we
      found that oral EP reduces bacterial burden during infection by Listeria
      monocytogenes, demonstrating its efficacy in vivo. EP initiates a signaling
      cascade within macrophages through both TLR4-dependent and -independent
      mechanisms, involving ERK, p38 and JNK, and ultimately the activation of NF
      kappaB.

PMID- 18618313
TI  - Lactobacillus acidophilus 74-2 and butyrate induce cyclooxygenase (COX)-1
      expression in gastric cancer cells.
AB  - Cyclo-oxygenase (COX) profile predicts prognosis of gastric cancer; COX-2
      positive tumors are more often aggressive, and COX-2 suppression is protective
      against gastric cancer. In contrast, COX-1 suppression is harmful to the
      intestinal mucosa. The COX-1, COX-2, and COX-1ir expression profiles were
      measured with real-time PCR in primary (AGS) and metastatic (NCI-N87) gastric
      adenocarcinoma cell lines treated with butyrate, hyperosmolar medium, and, in the
      case of NCI-N87, cell-free supernatants of probiotic bacteria Lactobacillus
      acidophilus 74-2 and Bifidobacterium lactis 420. The cell lines showed
      differences in the profile when treated with either hyperosmolar medium or
      butyrate. In NCI-N87 COX-2 expression was higher but only COX-1 expression was
      significantly upregulated by butyrate. Similarly to butyrate, the cell-free
      supernatant of L. acidophilus 74-2 upregulated COX-1, while COX-2 expression
      remained unchanged. COX-1ir, including COX-3, was upregulated by probiotics and
      osmotic stress. In conclusion, consumption of L. acidophilus 74-2 could be
      beneficial for the expression of cytoprotective COX-1.

PMID- 18618314
TI  - The effects of Fructus Xanthii extract on cytokine release from human mast cell
      line (HMC-1) and peripheral blood mononuclear cells.
AB  - In the present study, human mast cell line (HMC-1) and peripheral blood
      mononuclear cells (PBMNC) were pre-incubated with various concentrations of
      Fructus xanthii extract solution followed by being stimulated with phorbol
      myristate acetate and further incubated for 24 hours. The cytokines, in cell
      culture supernatants, of interleukin (IL)-4, IL-6, IL-8, GM-CSF, and TNF-alpha in
      the supernatant were measured by enzyme-linked immunosorbent assay. The results
      demonstrated that Fructus xanthii could modulate the mast cell-mediated and PBMNC
      mediated inflammatory and immunological reactions modulated by cytokines. And our
      study supplied the evidence of the mechanisms of Fructus Xanthii in treating
      inflammatory and allergic diseases.

PMID- 18618315
TI  - Mutation patterns in the chemokine CXC receptor 4 gene subfamily.
AB  - Six representative CXCR4 mRNAs of fish, amphibia, birds, and mammals were
      selected to study the pattern of conservation/mutation of the individual nt of
      the coding sequences. According to an arbitrary conservation index ranging from 1
      to 6, the indexes of conservation were: 5.04 for the first nt of coding triplets;
      5.34 for the second nt of triplets, and 3.75 for the third nt of triplets. The
      average conservation index of the individual triplets was 4.71. The conservation
      index of the seven hydrophobic transmembrane domains was 5.60, while the
      cumulative conservation index of the intracytoplasmic and extracellular domains
      was 4.63. Separate autocorrelation and power spectral analyses of the series of
      conservation indexes for the first nt, the second nt and the triplets
      demonstrated a modest "basic" positive correlation for about the first 20 lags
      and accordingly some power concentration at the lower frequencies (long periods).
      Within the triplets, the correlation was studied between the conservation indexes
      of nt 1 and 2, 1 and 3, and 2 and 3. Correlations of 1 with 3 and 2 with 3 were
      positive, but in the range of the basic local correlation, whereas the
      correlation between the first and second nt was significantly higher. This
      correlation, together with the higher conservation of the second nt as compared
      to the first (two patterns also found in the formyl peptide receptors), are
      likely to have been established by selection processes directed towards a
      functional conservation or a "functional repair."

PMID- 18618316
TI  - Prevalence of legume sensitization in patients with naso-bronchial allergy.
AB  - Prevalence of legume allergy and concomitant sensitization to different allergens
      was evaluated in patients of asthma and/ or rhinitis. Skin prick test with 27
      common food allergens and 61 aeroallergens in 76 subjects was performed. Out of
      76 subjects, 41 perceived allergenic problems with different food items as
      contributing factor. Only six patients showed prick test positivity compatible
      with their anamnesis. However, 35 subjects showed sensitization to different food
      items, out of which thirty were sensitive to legumes. The common foods in
      decreasing order of allergenicity were chickpea, followed by green gram, egg
      white, and bean fresh/red gram. Concomitant sensitization to different legume
      crops was found in patients.

PMID- 18618317
TI  - QSAR studies on peptide alpha-ketoamides and alpha-ketohydroxamate derivatives as
      calpain I inhibitors.
AB  - Quantitative Structure Activity Relationship (QSAR) studies were conducted on 34
      peptide alpha-ketoamide and alpha-ketohydroxamate derivatives of Calpain I using
      multiple linear regression (MLR) procedure. The activity contributions of these
      compounds were determined from regression equation and the validation procedures
      that analyze the predictive ability of QSAR models were described. Among forty
      six descriptors that were considered in generating the QSAR model, three
      descriptors such as LogP, Heat of formation and HOMO resulted in a statistically
      significant model with 0.877 r(2) and 0.937 q(2) respectively. The inter
      correlation between descriptors was 0.42. The proposed QSAR model indicates an
      increase in logP value increases hydrophobicity in order to achieve cellular
      permeability and an increase in heat of formation as well as decrease in HOMO
      energy favors better binding and activity towards development of potent calpain I
      inhibitors.

PMID- 18618318
TI  - Oleanolic acid and related derivatives as medicinally important compounds.
AB  - Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle
      after removal of organic bases and free acids. The literature survey revealed it
      to be biologically very important. In this review the biological significance of
      oleanolic acid and its derivatives has been discussed. The aim of this review is
      to update current knowledge on oleanolic acid and its natural and semisynthetic
      analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory,
      anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial,
      hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti
      angiogenic, antiallergic, antiviral and immunomodulatory activities. We present
      in this review, for the first time, a compilation of the most relevant scientific
      papers and technical reports of the chemical, pre-clinical and clinical research
      on the properties of oleanolic acid and its derivatives.

PMID- 18618319
TI  - Antidiabetic effect of an active fraction extracted from dragon's blood (Dracaena
      Cochinchinensis).
AB  - The active fraction extracted from dragon's blood displayed an inhibitory effect
      on alpha-glucosidase activity with an IC50 of 0.152 microg/mL, which is nearly
      half of the crude material. Its inhibition on alpha-glucosidase was
      noncompetitive. In addition, when this fraction was orally administered to mice
      dosed with Acarbose (20 mg/kg), the active fraction (100, 300, 500 mg/kg)
      significantly suppressed increase of blood glucose levels after sucrose loading
      in a dose-dependent manner. These results suggest that this extract from dragon's
      blood exerts an anti-diabetic effect by suppressing intestinal carbohydrate
      absorption and thereby reducing the postprandial increase of blood glucose.

PMID- 18618320
TI  - Benzo(a)pyrene-induced genotoxicity: attenuation by farnesol in a mouse model.
AB  - In the present study we have evaluated the antigenotoxic effects of Farnesol (FL)
      a 15-carbon isoprenoid alcohol against benzo (a) pyrene [B(a)P] (125 mg kg(-
      1).b.wt oral) induced toxicity. B(a)P administration lead to significant
      induction in Cytochrome P450 (CYP) content and aryl hydrocarbon hydrolase (AHH)
      activity (p < 0.001), DNA strand breaks and DNA adducts (p < 0.001) formation. FL
      was shown to suppress the activities of both CYP and AHH (p < 0.005) in modulator
      groups. FL pretreatment significantly (p < 0.001) restored depleted levels of
      reduced glutathione (GSH), quinone reductase (QR) and glutathione -S-transferase
      (GST). A simultaneous significant and at both the doses reduction was seen in DNA
      strand breaks and in in-vivo DNA adducts formation (p < 0.005), which gives some
      insight on restoration of DNA integrity. The results support the protective
      nature of FL. Hence present data supports FL as a future drug to preclude B (a) P
      induced toxicity.

PMID- 18618321
TI  - 4-phenyldiazenyl 2-(phenylimino methyl) phenols; synthesis and in-vitro
      biological evaluation as potential antibacterial agents.
AB  - A new series of 4-phenyldiazenyl 2-(phenylimino methyl) phenols were synthesized
      by the condensation of 5-[(2-chloro phenyl) diazenyl] 2-hydroxybenzaldehyde with
      different substituted aromatic amines and sulphonamides. All the synthesized
      compounds were screened in-vitro for their antibacterial activity against
      different human pathogens viz: B. anthracis, E.coli, S. aureus, S. typhimurium,
      and P. aeruginosa using disk diffusion assay. All the compounds exhibited
      considerable inhibition against the bacteria tested.

PMID- 18618322
TI  - Carbonic anhydrase inhibitors. Cloning, characterization and inhibition studies
      of the cytosolic isozyme III with anions.
AB  - The cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isozyme III (hCA III)
      has been cloned and purified by the GST-fusion protein method. Recombinant pure
      hCA III had the following kinetic parameters for the CO(2) hydration reaction at
      20 degrees C and pH 7.5: k(cat) of 1.3 x 10(4) s(- 1) and k(cat)/K(M) of
      2.5.10(5) M(- 1) s(- 1). The first detailed inhibition study of this enzyme with
      anions is reported. Inhibition data of the cytosolic isozymes hCA I - hCA III
      with a large number of anions (halides, pseudohalides, bicarbonate, carbonate,
      nitrate, nitrite, hydrosulfide, sulfate, sulfamic acid, sulfamide, etc.), were
      determined and these values are comparatively discussed for these three cytosolic
      isoforms. Fluoride, nitrate, nitrite, phenylboronic acid and phenylarsonic acid
      (as anions) were weak hCA III inhibitors (K(I)s of 21-78.5 mM), whereas
      bicarbonate, chloride, bromide, sulfate and several other simple anions showed
      K(I)s around 1 mM. The best hCA III inhibitors were carbonate, cyanide,
      thiocyanate, azide and hydrogensulfide, which showed K(I)s in the range of 10-90
      microM. It is difficult to explain the inhibitory activity of carbonate (K(I) of
      10 microM) against hCA III, also considering the fact that this ion has an
      affinity of 15-73 mM for hCA I and II and is in equilibrium with one of the
      substrates of this enzyme, i.e., bicarbonate, which is a much weaker inhibitor
      (K(I) of 0.74 mM against hCA III, of 12 mM against hCA I and of 85 mM against hCA
      II).

PMID- 18618323
TI  - Synthesis, anti-inflammatory, analgesic and antioxidant activities of some
      tetrasubstituted thiophenes.
AB  - Sets of tetrasubstituted thiophene esters 4a-4g, 5a-5f and 6a-6e were synthesized
      by reaction of 1-(alpha-Carbomethoxy-beta-aminothiocrotonoyl)-aryl/aroyl amines
      (3) with 3-(bromoacetyl)coumarin, 1,4-dibromodiacetyl and chloroacetone
      respectively. The compound 3 were synthesized by nucleophilic addition of
      aryl/aroylisothiocyanate and enamine (2). The synthesized targeted compounds (4a
      4g, 5a-5f and 6a-6e) were evaluated for their in vivo anti-inflammatory activity
      in carrageenin-induced rat hind paw oedema model at three graded doses employed
      at 10, 20 and 40 mg/kg body weight using mefanamic acid, ibuprofen and in vivo
      analgesic activity in acetic acid induced writhing response model at 10 mg/kg
      dose using ibuprofen as standard drug. The compounds 4a-4f, 5c, 5f, 6c and 6e
      were evaluated for their in vitro antioxidant nitric oxide radical scavenging
      assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 microg/mL using
      ascorbic acid as standard drug. Among all the targeted compounds 4c showed
      maximum anti-inflammatory activity of 71% protection at 10 mg/kg and 77%
      protection at 20 mg/kg to inflamed paw and analgesic activity of 56% inhibition
      and also maximum in vitro nitric oxide radical scavenging activity having IC(50)
      value 31.59 microg/mL.

PMID- 18618324
TI  - Amide derivatives with pyrazole carboxylic acids of 5-amino-1,3,4-thiadiazole 2
      sulfonamide as new carbonic anhydrase inhibitors: synthesis and investigation of
      inhibitory effects.
AB  - Pyrazole carboxylic acid amides of 5-amino-1,3,4-thiadiazole-2-sulfonamide were
      synthesized from 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonyl chloride and 4
      benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride. Carbonic
      anhydrase isoenzymes (hCA-I and hCA-II) were purified from human erythrocyte
      cells by the affinity chromatography method. The inhibitory effects of 5-amino
      1,3,4-thiadiazole-2-sulfonamide 1, acetazolamide 2 and new synthesized amides on
      these isozymes have been studied in vitro. The I(50) concentrations (the
      concentration of inhibitor producing a 50% inhibition of CA activity) against
      hydratase activity ranged from 1.2 to 2.2 nM for hCA-I and from 0.4 to 2 nM for
      hCA-II. The I(50) values against esterase activity ranged from 1.4 to 8 nM for
      hCA-I and from 1.3 to 6 nM for hCA-II. The K(i) values were observed between 8.2
      x 10(- 5) to 6.2 x 10(- 4) M for hCA-I and between 2.9 x 10(- 4) to 8.2 x 10(- 4)
      M for hCA-II. The comparison of new synthesized amides to 5-amino-1,3,4
      thiadiazole-2-sulfonamide 1, acetazolamide 2 indicated that the new synthesized
      compounds (18-23) inhibit CA activity more potently than the parent compounds.

PMID- 18618325
TI  - A new Schiff base copper (II) complex derived from estrone and d-glucosamine:
      Synthesis, characterization and its interaction with DNA.
AB  - A novel copper (II) complex of Schiff base prepared through condensation between
      2-formyl-17-deoxyestrone and d-glucosamine was synthesized and characterized.
      Fluorescence spectroscopy was conducted to assess their binding ability with CT
      DNA. The results showed that the copper (II) complex could bind to DNA with a
      weak intercalative mode. The interaction between the copper (II) complex and DNA
      was also investigated by gel electrophoresis. Interestingly, we found that the
      complex could cleave plasmid DNA (pUC19) to nicked and linear forms through an
      oxidative mechanism without the use of exogenous agents.

PMID- 18618326
TI  - Synthesis and characterization of biologically significant 5,5'-(1,4
      phenylene)bis(1-N-alkoxyphthalimido-3-aryl-2-pyrazoline) derivatives.
AB  - A facile synthesis of 5,5'-(1,4-phenylene)bis(3-aryl-2-pyrazolines) 4a-g has been
      achieved by the cyclo-addition reaction of hydrazine hydrate with bis-substituted
      chalcones 3a-g, which in turn were prepared by the Clasien-Schmidt condensation
      of p-substituted acetophenones 1a-g with terephthaldehyde. Condensation of 4a-g
      with omega-bromoalkoxyphthalimides 5a-b afforded the titled compounds 6a-n, some
      of which exhibited significant antimalarial as well as antimicrobial activity.

PMID- 18618327
TI  - Aluminium(III), chromium(III) and iron(III) complexes with 5-iodouracil and 5
      iodouracil-histidine and their antitumour activity.
AB  - Complexes of the type [Al(HL)(OH)Cl(2)], [M(HL)(OH)(2)Cl] and [M'(HL)(L')(OH)Cl],
      where HL = 5-iodouracil; HL' = histidine; M = Cr(III), Fe(III) and M' = Al(III),
      Cr(III), Fe(III), were synthesized and characterized. The complexes are polymeric
      showing high decomposition points and are insoluble in water and common organic
      solvents. The mu(eff) values, electronic spectral bands and ESR spectra suggest a
      polymeric 6-coordinate spin-free octahedral stereochemistry for the Cr(III) and
      Fe(III) complexes. 5-Iodouracil acts as a monodentate ligand coordinating to the
      metal ion through the O atom of C((4)) = O while histidine through the O atom of 
      COO(- ) and the N atom of -NH(2) group. In vivo antitumour effect of 5-iodouracil
      and its complexes was examined on C(3)H /He mice against P815 murine mastocytoma.
      As evident from their T/C values, Cr(III) and Fe(III) complexes display
      significant and higher antitumour activity compared to the 5-iodouracil ligand.
      The in vitro results of the complexes on the same cells indicate that Cr(III) and
      Fe(III) complexes show higher inhibition on (3)H-thymidine and (3)H-uridine
      incorporation in DNA and RNA replication, respectively, at a dose of 5 microg/mL.

PMID- 18618332
TI  - Methods to assess gastric motility and sensation.

PMID- 18618331
TI  - Optimization and in vivo evaluation of an oral dual controlled-release tablet
      dosage form of insulin and duck ovomucoid.
AB  - The objectives of the present study were to (1) optimize the release rate of
      insulin from compressed microparticulates and (2) compare the in vivo
      hypoglycemic effect of optimized insulin microparticulates with compressed enzyme
      inhibitor (duck ovomucoid) and without inhibitor. A 3-factor, 15-run Box Behnken
      design was used to construct polynomial models correlating the dependent and
      independent variables. Independent processing variables were rate of addition of
      the alcoholic Eudragit L100 dispersion, volume of the antisolvent, and
      compression pressure. Responses were cumulative percent of insulin released from
      1-6 hours. Insulin and ovomucoid release was simultaneously analyzed by high
      performance liquid chromatography. They demonstrated variable release rates,
      which were optimized to the Higuchi's square root of time model to release the
      insulin and the inhibitor over 6 hours. The relationship between dissolution
      profiles and process parameters were demonstrated by contour and response surface
      plots. In vivo hypoglycemic effect was evaluated in rabbits in a 3-way crossover
      design. Cocompressed microparticulates of insulin and duck ovomucoid displayed a
      3.2-fold greater hypoglycemic effect when compared with a similar preparation
      without ovomucoid. This study demonstrated the potential benefits of dosage forms
      with dual controlled-release mechanisms for both the protein and enzyme
      inhibitor.

PMID- 18618333
TI  - Germinated barley foodstuff ameliorates inflammation in mice with colitis through
      modulation of mucosal immune system.
AB  - OBJECTIVE: Germinated barley foodstuff (GBF) is a prebiotic product made from
      malt which contains glutamine-rich protein and hemicellulose-rich fiber. Although
      GBF has been observed to attenuate colonic mucosal inflammation and bowel
      movements in ulcerative colitis, both experimentally and clinically, the details
      of the immune response remain elusive. The aim of this study was to investigate
      the effects of GBF on the colonic epithelium immune response in a CD45RB(high) T
      cell chronic colitis model. MATERIAL AND METHODS: Colitis was induced by
      transferring CD4+ CD45RB(high) T cells to severe combined immunodeficiency (SCID)
      mice (control n=8, GBF n=8) and the effects of GBF on the colitis were evaluated.
      The evaluation included measurement of body-weight, occult blood tests,
      histological examination, mucosal cytokine reverse transcription-polymerase chain
      reaction (RT-PCR) analysis (interferon-gamma (IFN-gamma), transforming growth
      factor-beta (TGF-beta)) as well as IL-6 measurements. RESULTS: Seven weeks after
      transferring the above cells, body-weight loss and occult blood were
      significantly reduced in the mice that had been fed with GBF. In these mice,
      there were also significant reductions in IFN-gamma mRNA expressions and IL-6 in
      the colonic mucosa, as compared with the control group. GBF also significantly
      attenuated, mucosal damage and mucin positive goblet cell depletion. Conversely,
      TGF-beta expression significantly increased in the GBF group, compared with the
      control group. CONCLUSIONS: In this preliminary study using an experimental model
      in which colitis was induced by transferring CD4+ CD45RB(high) T cells to SCID
      mice, GBF reduced inflammation by modulating the colonic microflora.

PMID- 18618334
TI  - Usefulness of RT-PCR for the diagnosis of Japanese encephalitis in clinical
      samples.
AB  - The present study was carried out between July 2003 and December 2005 in PGIMER,
      Chandigarh, India and aimed to compare IgM capture ELISA and nested RT-PCR for
      the diagnosis of Japanese encephalitis (JE). The samples collected were
      cerebrospinal fluid and blood from 40 febrile patients with encephalitis (n=40,
      group I) and blood samples from febrile patients without encephalitis residing in
      JE endemic areas (n=45, group II). Overall, in CSF samples JE specific RNA was
      detected in 9/40 (22.5%), while 7/28 (25%) patients showed the presence of
      specific IgM antibodies. Only 28 CSF samples could be subjected to both RT-PCR
      and IgM and, among these, 13 cases were found to be confirmed JE based on IgM
      and/or RT-PCR positivity. Among the confirmed cases, 6 (6/13, 46.5%) could be
      detected by RT-PCR alone, 4 (4/13, 30.7%) by IgM capture ELISA and 3 (3/13,
      23.1%) patients were positive by both the methods. All the RT-PCR positive cases
      had presented within 5 d of onset of illness. The serum samples of only 16
      patients in group I could be tested for IgM antibodies and 5 (31.25%) were found
      to be positive, while in group II, 11.1% (5/45) positivity was observed. JE
      specific RNA could not be detected in serum samples of either group of patients.
      This study highlights the need for carrying out RT-PCR in CSF samples, compared
      to IgM antibody detection, for the early detection of JEV.

PMID- 18618335
TI  - Cytomegalovirus-associated idiopathic thrombocytopenic purpura in Chinese
      children.
AB  - The objective was to investigate the clinical features, glycoprotein B (gB)
      genotype and therapy of the human cytomegalovirus (CMV)-associated idiopathic
      thrombocytopenic purpura (ITP) in Chinese children. Clinical features and
      laboratory data of 25 CMV-associated ITP, including 18 males and 7 females with a
      median age of 0.3 y, were analysed and compared with 116 CMV-negative ITP. The
      CMV gB of 17 cases was genotyped. Apart from dermatorrhagia, jaundice was noted
      in 6 cases. Cough, diarrhoea, fever, splenohepatomegaly, alimentary tract
      haemorrhage and raised ALT were also found. Compared with CMV-negative ITP, CMV
      associated ITP has a younger median age, raised ALT and AST, and longer
      hospitalization (p<0.05, respectively). The most prevalent genotype was gB1
      (15/17), followed by coinfection and gB3. Compared with congenitally CMV-infected
      children in our previous study, more prevalence of gB1 was noted (40/79 vs 15/17,
      p=0.004). Most of these cases were receiving the therapy of immunoglobulin,
      corticoid and/or gancyclovir with good therapeutic effect except for 2 cases. In
      conclusion, CMV infection, especially gB1 genotype, is an important cause of ITP
      and careful examination of markers of CMV in all cases of apparent 'idiopathic'
      ITP is required. Combination therapy of immunoglobulin, corticoid and gancyclovir
      is effective.

PMID- 18618336
TI  - Formaldehyde exposure in U.S. industries from OSHA air sampling data.
AB  - National occupational exposure databanks have been cited as sources of exposure
      data for exposure surveillance and exposure assessment for occupational
      epidemiology. Formaldehyde exposure data recorded in the U.S Integrated
      Management Information System (IMIS) between 1979 and 2001 were collected to
      elaborate a multi-industry retrospective picture of formaldehyde exposures and to
      identify exposure determinants. Due to the database design, only detected
      personal measurement results (n = 5228) were analyzed with linear mixed-effect
      models, which explained 29% of the total variance. Short-term measurement results
      were higher than time-weighted average (TWA) data and decreased 18% per year
      until 1987 (TWA data 5% per year) and 5% per year (TWA data 4% per year) after
      that. Exposure varied across industries with maximal estimated TWA geometric
      means (GM) for 2001 in the reconstituted wood products, structural wood members,
      and wood dimension and flooring industries (GM = 0.20 mg/m(3). Highest short-term
      GMs estimated for 2001 were in the funeral service and crematory and
      reconstituted wood products industries (GM = 0.35 mg/m(3). Exposure levels in
      IMIS were marginally higher during nonprogrammed inspections compared with
      programmed inspections. An increasing exterior temperature tended to cause a
      decrease in exposure levels for cold temperatures (-5% per 5 degrees C for T < 15
      degrees C) but caused an increase in exposure levels for warm temperatures (+15%
      per 5 degrees C for T >15 degrees C). Concentrations measured during the same
      inspection were correlated and varied differently across industries and sample
      type (TWA, short term). Sensitivity analyses using TOBIT regression suggested
      that the average bias caused by excluding non-detects is approximately 30%, being
      potentially higher for short-term data if many non-detects were actually short
      term measurements. Although limited by availability of relevant exposure
      determinants and potential selection biases in IMIS, these results provide useful
      insight on formaldehyde occupational exposure in the United States in the last
      two decades. The authors recommend that more information on exposure determinants
      be recorded in IMIS.

PMID- 18618337
TI  - Mirtazapine, a noradrenergic and specific serotonergic antidepressant, attenuates
      morphine dependence and withdrawal in Sprague-Dawley rats.
AB  - The effects of mirtazapine, a noradrenergic and specific serotonergic
      antidepressant, on morphine withdrawal and morphine conditioned place preference
      (CPP) were investigated in rats. Our results showed that some morphine withdrawal
      signs, including teeth chattering, grooming, chewing, and escape attendance, were
      attenuated by single pretreatments with 3, 10, or 30 mg/kg mirtazapine. Wet-dog
      shakes, rearing, and grooming were inhibited by daily pretreatment with 1, 3, or
      10 mg/kg mirtazapine. The expression of morphine-induced CPP was significantly
      blocked by mirtazapine (10 or 30 mg/kg, i.p.), while chronic treatment with
      mirtazapine (1 or 10 mg/kg, i.p. once, daily, for six consecutive days)
      significantly attenuated the acquisition of morphine CPP. Our results
      demonstrated that mirtazapine attenuates morphine withdrawal and morphine-induced
      CPP in rats and suggest that mirtazapine may have therapeutic potential in the
      treatment of opiate dependence.

PMID- 18618338
TI  - Drug treatment outcomes for persons on waiting lists.
AB  - This study examined treatment access and outcomes for persons placed on drug
      abuse treatment waiting lists. Participants (n = 170) were recruited when they
      entered either a methadone detoxification program or a day treatment program, and
      were waiting for methadone maintenance or residential treatment, respectively.
      Participants were interviewed at baseline and 2-months follow-up. Excluding the
      index treatment episode, 73% received some treatment during the follow-up period.
      Mixed effects regression was used to compare short-term outcomes for clients who
      did and did not enter treatment following the index episode. We found increased
      drug problems, over time, for all participants. Those enrolled in treatment at
      follow-up reported higher employment problems (collapsed across time) compared
      with those not in treatment. Last, participants enrolled in any subsequent
      treatment showed a decrease in psychiatric problems over time, while those not
      enrolled in subsequent treatment showed an increase in psychiatric problems.
      Participants who entered treatment within 60 days after being placed on a waiting
      list showed improvement on psychiatric measures but not on substance abuse
      measures.

PMID- 18618340
TI  - Oxaliplatin-induced long QT syndrome in a patient with appendiceal
      adenocarcinoma.

PMID- 18618339
TI  - Light- and time-dependent polymerization of dual-cured resin luting agent beneath
      ceramic.
AB  - OBJECTIVE: In this study we investigated the degree of conversion (DC) of a dual
      cured resin luting agent beneath a ceramic of different thickness. MATERIAL AND
      METHODS: The luting material (RelyX) was photo-activated for 40s through ceramic
      disks (Empress Esthetic, 0.7, 1.4, or 2mm thick). Dual (DUC) and chemically cured
      (CC) control groups were obtained. A delayed exposure (DE) procedure was tested
      in which the material was light-activated after 5 min without using ceramic. DC
      (%) was measured using infrared spectroscopy at 40 s, 1, 2, 4, 6, 8, and 10 min.
      Light irradiance and spectrum transmitted through ceramic were measured using a
      power meter and a spectrometer. RESULTS: A decrease in irradiance was detected
      with increasing ceramic thickness, but no alteration in the emission profile was
      observed. At 10 min, all groups showed DC higher than at 40s. No significant
      differences were detected for DUC compared with the groups indirectly activated
      through the ceramic disks. Generally, CC showed the lowest DC values. No
      significant effect in DC was detected for DE after 10 min. A significant increase
      in DC was generally detected only up to 4 min. CONCLUSIONS: The luting agent was
      dependent on light exposure and time to obtain improved DC. Neither the indirect
      activation nor the DE procedure significantly influenced the final DC.

PMID- 18618341
TI  - A new fiducial marker for Image-guided radiotherapy of prostate cancer: clinical
      experience.
AB  - BACKGROUND: A new fiducial marker for image guided radiotherapy (IGRT) based on a
      removable prostate stent made of Ni Ti has been developed during two previous
      clinical feasibility studies. The marker is currently being evaluated for IGRT
      treatment in a third clinical study. METHOD: The new marker is used to co
      register MR and planning CT scans with high accuracy in the region around the
      prostate. The co-registered MR-CT volumes are used for delineation of GTV before
      planning. In each treatment session the IGRT system is used to position the
      patient before treatment. The IGRT system use a stereo pair of kV images matched
      to corresponding Digital Reconstructed Radiograms (DRR) from the planning CT
      scan. The match is done using mutual gray scale information. The pair of DRR's
      for positioning is created in the IGRT system with a threshold in the Look Up
      Table (LUT). The resulting match provides the necessary shift in couch
      coordinates to position the stent with an accuracy of 1-2 mm within the planned
      position. RESULTS: At the present time 39 patients have received the new marker.
      Of the 39 one has migrated to the bladder. Deviations of more than 5 mm between
      CTV outlined on CT and MR are seen in several cases and in anterior-posterior
      (AP), left-right (LR) and cranial-caudal (CC) directions. Intra-fraction
      translation movements up to +/- 3 mm are seen as well. As the stent is also
      clearly visible on images taken with high voltage x-rays using electronic portal
      images devices (EPID), the positioning has been verified independently of the
      IGRT system. DISCUSSION: The preliminary result of an on going clinical study of
      a Ni Ti prostate stent, potentially a new fiducial marker for image guided
      radiotherapy, looks promising. The risk of migration appears to be much lower
      compared to previous designs.

PMID- 18618342
TI  - DCEMRI monitoring of canine tumors during fractionated radiotherapy.
AB  - PURPOSE: To monitor the contrast enhancement in spontaneous canine tumors during
      fractionated radiotherapy by Dynamic Contrast Enhanced Magnetic Resonance Imaging
      (DCEMRI). METHODS AND MATERIAL: Six dogs with tumors in the oral or nasal cavity
      received fractionated conformal radiotherapy with 54 Gy given in 18 fractions. T1
      weighted DCE imaging was performed prior to each treatment fraction. The tumor
      was manually delineated in the MR images following every imaging session, and the
      time dependence of the Relative Signal Intensity (RSI) in the tumor was extracted
      voxel by voxel. RSI images at the time of maximum enhancement were generated, in
      addition to images of the initial slope of the RSI curves. The dependence of the
      median RSI and median slope in the tumor on the accumulated radiation dose was
      investigated, and images obtained at different treatment fraction were compared
      by correlation analysis. RESULTS: Five of the six tumors regressed during
      treatment. The dose dependence of the RSI varied between the tumors, with some
      showing an increase and others a decrease in RSI with dose. This was also the
      case for the initial slope of the RSI curves. The correlation between images
      acquired before the first treatment fraction and subsequent fractions was in
      general low, and decreased significantly with accumulated radiation dose for five
      of six tumors. CONCLUSIONS: Large individual variations in the dose response of
      tumor contrast enhancement were found. Decreasing image correlation resulted both
      from tumor regression and intratumoral changes in the RSI distribution during
      treatment. These findings may have consequences for treatment design in
      biological image-guided radiotherapy.

PMID- 18618343
TI  - An overview of volumetric imaging technologies and their quality assurance for
      IGRT.
AB  - Image-guided radiation therapy (IGRT) aims at frequent imaging in the treatment
      room during a course of radiotherapy, with decisions made on the basis of this
      information. The concept is not new, but recent developments and clinical
      implementations of IGRT drastically improved the quality of radiotherapy and
      broadened its possibilities as well as its indications. In general IGRT solutions
      can be classified in planar imaging, volumetric imaging using ionising radiation
      (kV- and MV- based CT) or non-radiographic techniques. This review will focus on
      volumetric imaging techniques applying ionising radiation with some comments on
      Quality Assurance (QA) specific for clinical implementation. By far the most
      important advantage of volumetric IGRT solutions is the ability to visualize soft
      tissue prior to treatment and defining the spatial relationship between target
      and organs at risk. A major challenge is imaging during treatment delivery. As
      some of these IGRT systems consist of peripheral equipment and others present
      fully integrated solutions, the QA requirements will differ considerably. It
      should be noted for instance that some systems correct for mechanical
      instabilities in the image reconstruction process whereas others aim at optimal
      mechanical stability, and the coincidence of imaging and treatment isocentre
      needs special attention. Some of the solutions that will be covered in detail
      are: (a) A dedicated CT-scanner inside the treatment room. (b) Peripheral systems
      mounted to the gantry of the treatment machine to acquire cone beam volumetric CT
      data (CBCT). Both kV-based solutions and MV-based solutions using EPIDs will be
      covered. (c) Integrated systems designed for both IGRT and treatment delivery.
      This overview will explain some of the technical features and clinical
      implementations of these technologies as well as providing an insight in the
      limitations and QA procedures required for each specific solution.

PMID- 18618345
TI  - Clinical significance of quantitative analysis of facial nerve enhancement on MRI
      in Bell's palsy.
AB  - CONCLUSIONS: Quantitative analysis of the facial nerve on the lesion side as well
      as the normal side, which allowed for more accurate measurement of facial nerve
      enhancement in patients with facial palsy, showed statistically significant
      correlation with the initial severity of facial nerve inflammation, although
      little prognostic significance was shown. OBJECTIVES: This study investigated the
      clinical significance of quantitative measurement of facial nerve enhancement in
      patients with Bell's palsy by analyzing the enhancement pattern and correlating
      MRI findings with initial severity of facial palsy and clinical outcome. SUBJECTS
      AND METHODS: Facial nerve enhancement was measured quantitatively by using the
      region of interest on pre- and postcontrast T1-weighted images in 44 patients
      diagnosed with Bell's palsy. The signal intensity increase on the lesion side was
      first compared with that of the contralateral side and then correlated with the
      initial degree of facial palsy and prognosis. RESULTS: The lesion side showed
      significantly higher signal intensity increase compared with the normal side in
      all of the segments except for the mastoid segment. Signal intensity increase at
      the internal auditory canal and labyrinthine segments showed correlation with the
      initial degree of facial palsy but no significant difference was found between
      different prognostic groups.

PMID- 18618346
TI  - Ruptured aneurysm of noncoronary sinus of Valsalva: demonstration with magnetic
      resonance imaging.
AB  - There are few published reports regarding imaging findings of sinus of Valsalva
      aneurysms (SVA) with magnetic resonance imaging (MRI). We present an unusual form
      of ruptured SVA, emphasizing the diagnostic importance of MRI among a range of
      imaging techniques. This case report describes a case of idiopathic (thought to
      be congenital in origin), acutely symptomatic ruptured noncoronary SVA diagnosed
      by MRI and confirmed with conventional angiography and surgery. MRI accurately
      showed aneurysm size, location, and rupture into the right atrium and provided
      valuable information about this rare lesion.

PMID- 18618347
TI  - Diagnostic value of ex-vivo three-dimensional micro-computed tomography imaging
      of primary nonhematopoietic human bone tumors: osteosarcoma versus
      chondrosarcoma.
AB  - BACKGROUND: Osteosarcoma and chondrosarcoma are the most common nonhematopoietic
      primary malignancies of bone. However, unusual radiographic appearances can lead
      to delay in diagnosis and confusion with benign diseases. PURPOSE: To evaluate
      the feasibility of micro-computed tomography (CT) for the analysis of primary,
      nonhematopoietic human bone tumors ex vivo. MATERIAL AND METHODS: Samples from 12
      human bone specimens (osteosarcoma, n=6; chondrosarcoma, n=6) obtained for
      diagnostic purposes were scanned using industrial X-ray film without amplifier
      foil and scanned with micro-CT (7- and 12-microm-cubic voxels). Trabecular bone
      CT "density" and tumor matrix CT "density" were determined, and results were
      compared with those obtained from a detailed conventional histopathologic
      analysis of corresponding cross-sections. The significance of differences in
      grayscale measurements was tested with analysis of variance. RESULTS: Micro-CT
      provided quantitative information on bone morphology equivalent to
      histopathological analysis. We established grayscale measurements by which tumor
      matrices of chondrosarcoma and osteosarcoma could be radiographically categorized
      following histological classifications (P<0.001). CONCLUSION: Micro-CT is
      feasible for the analysis and differentiation of human osteosarcoma and
      chondrosarcoma.

PMID- 18618349
TI  - A novel radiofrequency thermocoagulation method for treatment of lower back pain:
      thermal conduction after instillation of saline solution into the nucleus
      pulposus--preliminary results.
AB  - BACKGROUND: Radiofrequency heating of the intervertebral disc has been proposed
      for the treatment of chronic low back pain using two methods: a flexible needle
      inserted into the annulus fibrosus achieving a full 360 degrees penetration, or a
      rigid needle inserted into the nucleus pulposus. The first technique is effective
      on pain, but the clinical benefit of the second is uncertain. PURPOSE: To
      evaluate a technique for radiofrequency heating of the lumbar intervertebral disc
      by a needle placed into the nucleus pulposus. MATERIAL AND METHODS: The method
      was tested in 17 patients according to the criteria used in previous intradiscal
      radiofrequency studies. Before and after treatment, disability was assessed by
      the Oswestry disability score. A pain reduction of at least 50% was considered a
      success. RESULTS: Fifteen patients were responders at 1 month (88%), nine at 3
      months (53%), and 12 at 6 months (70.6%). No complications were observed.
      CONCLUSION: A new method of providing discal radiofrequency treatment for lower
      back pain had a substantial clinical benefit in 71% of the observed patients. A
      prospective study comparing this new method with placebo should be conducted to
      confirm these initial results.

PMID- 18618350
TI  - Reader accuracy and confidence in diagnosing diffuse lung disease on high
      resolution computed tomography of the lungs: impact of sampling frequency.
AB  - BACKGROUND: The accuracy of the number of high-resolution computed tomography
      (HRCT) images necessary to diagnose diffuse lung disease (DLD) is not well
      established. PURPOSE: To evaluate the impact of HRCT sampling frequency on reader
      confidence and accuracy for diagnosing DLD. MATERIAL AND METHODS: HRCT images of
      100 consecutive patients with proven DLD were reviewed. They were: 48 usual
      interstitial pneumonia, 22 sarcoidosis, six hypersensitivity pneumonitis, five
      each of desquamative interstitial pneumonitis, eosinophilic granulomatosis, and
      lymphangioleiomyomatosis, and nine others. Inspiratory images at 1-cm increments
      throughout the lungs and three specified levels formed complete and limited
      examinations. In random order, three experts (readers 1, 2, and 3) ranked their
      top three diagnoses and rated confidence for their top diagnosis, independently
      and blinded to clinical information. RESULTS: Using the complete versus limited
      examinations for correct first-choice diagnosis, accuracy for reader 1 (R1) was
      81% versus 80%, respectively, for reader 2 (R2) 70% versus 70%, and for reader 3
      (R3) 64% versus 59%. Reader accuracy within their top three choices for complete
      versus limited examinations was: R1 91% versus 91% of cases, respectively, R2 84%
      versus 83%, and R3 79% versus 72% of cases. No statistically significant
      differences were found between the diagnosis methods (P=0.28 for first diagnosis
      and P=0.17 for top three choices). The confidence intervals for individual raters
      showed considerable overlap, and the point estimates are almost identical. The
      mean interreader agreement for complete versus limited HRCT for both top and top
      three diagnoses were the same (moderate and fair, respectively). The mean
      intrareader agreement between complete and limited HRCT for top and top three
      diagnoses were substantial and moderate, respectively. CONCLUSION: Overall reader
      accuracy and confidence in diagnosis did not significantly differ when fewer or
      more HRCT images were used.

PMID- 18618351
TI  - Problem solving skills predict quality of life and psychological morbidity in ALS
      caregivers.
AB  - Amyotrophic lateral sclerosis (ALS) often is associated with a particularly
      intensive caregiving experience, and the well-being of caregivers impacts that of
      patients. Thus, identification of factors leading to distress in caregivers may
      provide avenues for intervention that will help both the caregiver and the
      patient. We prospectively examined caregivers' social problem solving skills, the
      quality of the patient-caregiver relationship, caregivers' spirituality and
      religiousness, and the ways in which these impact caregivers' quality of life
      (QoL) and psychological morbidity in 75 caregivers of ALS patients. Data were
      analyzed through correlational and hierarchical multiple regression analyses.
      Social problem solving and spirituality were the best predictors of caregivers'
      QoL, accounting for 15.6% and 7.8% of the variance in QoL, respectively (F (2,
      69) = 11.83, p<.001). Social problem solving also predicted and accounted for
      25.4% of the variance in psychological morbidity (F (1, 71) = 25.571, p<.001).
      Level of care provided did not predict either QoL or psychological morbidity in
      caregivers. In conclusion, the problem-solving skills of ALS caregivers are an
      important determinant of caregiver well-being. Developing interventions to teach
      ALS caregivers effective methods of problem solving would probably be beneficial
      to this population.

PMID- 18618352
TI  - Circulating preptin levels in normal, impaired glucose tolerance, and type 2
      diabetic subjects.
AB  - BACKGROUND: Preptin is a novel hormone that is co-secreted with insulin and
      amylin from the pancreatic beta-cells. Preptin increases glucose-mediated insulin
      secretion, while the binding of endogenous preptin by antipreptin antibodies
      decreases glucose-mediated insulin secretion. Thus, it appears to act as a
      physiological amplifier of glucose-mediated insulin secretion. Aim. In this
      study, we investigate whether plasma preptin levels are different in non-diabetic
      subjects and patients with impaired glucose tolerance (IGT) or type 2 diabetes
      mellitus (T2DM). METHOD: Fifty patients with T2DM, 56 subjects with IGT, and 54
      sex- and age-matched normal controls participated in the study. Plasma preptin
      levels were measured with a radioimmunoassay. The relationships between plasma
      preptin levels and anthropometric and metabolic parameters were also assessed.
      RESULTS: Plasma preptin levels were higher in patients with T2DM compared to
      patients with IGT and controls (456+/-14 versus 416+/-13 and 398+/-13 ng/L,
      P<0.05 and P<0.01, respectively). Plasma preptin levels were lower in males than
      females (403+/-10 versus 432+/-10 ng/L, P<0.05). Fasting plasma preptin levels
      correlated positively with diastolic blood pressure (DBP) (r=0.20, P<0.01),
      triglyceride (TG) (r=0.24, P<0.01), total cholesterol (TC) (r=0.24, P<0.01), high
      density lipoprotein cholesterol (HDL-C) (r=0.18, P<0.05), free fatty acids (FFA)
      (r=0.21, P<0.01), 2-h blood glucose after glucose overload (2hOGTT) (r=0.18,
      P<0.05), glycosylated haemoglobin (HbA(1)c) (r=0.19, P<0.01), and homeostasis
      model assessment-insulin resistance index (HOMA(IR)) (r=0.13, P<0.05) in simple
      regression analysis of pooled data, while in multiple stepwise regression
      analysis, only DBP, TG, HDL-C, and FFA were independently related with plasma
      preptin levels. CONCLUSION: The present work suggests a potential role of preptin
      in the pathogenesis of T2DM.

PMID- 18618353
TI  - Soluble, platelet-bound, and total P-selectin as indices of platelet activation
      in congestive heart failure.
AB  - BACKGROUND: Many complications associated with congestive heart failure (CHF)
      have a thrombosis-related aetiology. Platelets play an important role in
      thrombogenesis, but it is not clear whether circulating platelets actively
      participate in thrombosis-related complications associated with CHF. OBJECTIVE:
      To determine whether soluble P-selectin, platelet surface P-selectin, and total
      platelet P-selectin as indices of platelet activation in CHF patients-compared to
      'disease controls' and 'healthy controls'-and to assess their prognostic value in
      CHF. METHODS: We measured soluble P-selectin (sP-sel, by enzyme-linked
      immunosorbent assay, ELISA), total platelet P-selectin (pP-sel, by a novel
      'platelet lysate' assay), platelet surface P-selectin (CD62P%G) and platelet
      surface CD63 (CD63%G) expression by flow cytometry-in 108 patients with stable
      congestive heart failure (all with left ventricular ejection fraction (LVEF)
      <50%). Levels were compared with 50 healthy controls and 70 'disease controls'
      (patients with coronary artery disease with normal left ventricular systolic
      function). RESULTS: CHF patients and disease controls had higher sP-sel, CD62P%G
      and CD63%G than healthy controls. There were no significant correlations between
      sP-sel, pP-sel, CD62P%G and CD63%G with ejection fraction (all P>0.05). There
      were no differences in these markers when ischaemic and non-ischaemic aetiologies
      of CHF were compared. After a median follow-up of 490 days (range 340-535), there
      were 7 deaths, 15 hospitalizations for worsening heart failure, 1 for cardiac
      resynchronization therapy, 4 for revascularizations, 4 for myocardial
      infarctions, and 1 stroke. None of the platelet markers were predictive of the
      composite end-point at follow-up. CONCLUSIONS: Patients with stable CHF exhibit
      evidence of abnormal platelet activation, despite usage of antiplatelet agents.
      These abnormalities did not determine prognosis and were broadly similar to those
      seen in 'disease controls' indicating that platelet abnormalities in CHF may
      simply be related to associated comorbidities.

PMID- 18618354
TI  - G protein-coupled receptor kinase 2 (GRK2) in migration and inflammation.
AB  - G protein-coupled receptor kinase 2 (GRK2) is a key modulator of G protein
      coupled receptors and other plasma membrane receptors stimulated by chemotactic
      messengers. On top of that, GRK2 has been reported to interact with a variety of
      signal transduction proteins related to cell migration such as MEK, Akt,
      PI3Kgamma or GIT. Interestingly, the levels of expression and activity of this
      kinase are altered in a number of inflammatory disorders (as rheumatoid arthritis
      or multiple sclerosis), thus suggesting that it may play an important role in the
      onset or development of these pathologies. This review summarizes the mechanisms
      involved in the control of GRK2 expression and function and highlights novel
      functional interactions of this protein that might help to explain how altered
      GRK2 levels affects cell migration in different cell types and pathological
      settings.

PMID- 18618355
TI  - A psychoneuroendocrino-immune approach in the nursing treatment of anorexia and
      bulimia nervosa.
AB  - Recent clinical reports have shown an increasing number of patients afflicted by
      eating disorders in the western world. There are numerous causes and mechanisms
      leading to eating disorders that affect the psychoneuroendocrinoimmune system. In
      this study, we define a novel psychoneuroendocrinoimmune nursing approach for
      anorexic and bulimic patients' treatment. According to the specific diagnostic
      items deriving from the Diagnostic and Statistical Manual of Mental Disorders and
      the International Classification of Diseases, and clinical guidelines in eating
      disorders formulated by the National Institute for Clinical Excellence, we
      carried out a qualitative study on the nursing treatment chosen by 210
      international centers considered as a sample. This study was based on a no
      structured interview via e-mail to better understand the nursing approach in
      anorexia and bulimia nervosa. Thanks to the selected centers' answers, four
      different levels of nursing care were identified, that include: the nursing role
      analyzing the spectrum of patients' problems; the nursing intervention in
      inpatient care; the nursing intervention in outpatient care; the day hospital
      treatment. All four prove to be especially useful in the nursing practice.

PMID- 18618356
TI  - The significance of mild traumatic brain injury to cognition and self-reported
      symptoms in long-term recovery from injury.
AB  - The aim of this study was to evaluate neurocognition and self-reported symptoms
      in long-term recovery from mild traumatic brain injury (mild TBI). Participants'
      time since injury ranged from 3 to 72 (M = 36.75) months. Relative to orthopedic
      injury controls (n = 63), mild TBI participants (n = 63) did not demonstrate
      cognitive impairment in any domains examined, or differences in self-report of
      postconcussive or psychiatric symptoms. However, postconcussive and psychiatric
      symptoms were strongly related (r = .50, p < .05). Results provide additional
      evidence that neurological injury in single-incident mild TBI is of little
      clinical significance to long-term cognitive and symptom outcome.

PMID- 18618357
TI  - Numerical abilities in Williams syndrome: dissociating the analogue magnitude
      system and verbal retrieval.
AB  - Two numerical systems--the analogue magnitude system and verbal retrieval--were
      investigated in Williams syndrome (WS) with three numerical tasks: simple
      addition, simple multiplication, and number comparison. A new matching technique
      was introduced in selecting the proper control groups. The WS group was
      relatively fast in the addition and multiplication tasks, but was slow in number
      comparison. No reverse numerical effect was observed in the comparison task, and
      the distance effect was stronger than that in the control groups. The findings
      indicate a profile with an impaired analogue magnitude system and less impaired
      verbal retrieval in Williams syndrome.

PMID- 18618358
TI  - Ambiguous idiom comprehension in Alzheimer's disease.
AB  - Ambiguous idiom comprehension was examined in 15 patients with mild probable
      Alzheimer's disease (AD) by means of two tasks: a string-to-picture matching task
      and a string-to-word matching task. In the first, patients had to choose among
      four pictures, while in the second they chose among four words. For both tasks
      the alternatives were the picture/word corresponding to the figurative meaning, a
      semantic associate (picture/word) to the last word of the idiom, and two
      unrelated alternatives, which were, in the case of words, an unrelated foil
      preserving the semantic class and a literal continuation foil (a word that can
      follow the verb in that sentence), while in the case of pictures the first was
      substituted by an unrealistic foil. The patients were also submitted to three
      language, one visuo-perceptual, and two executive tasks. Idiom comprehension was
      poor, particularly when the string-to-picture matching task was used, and
      correlated with executive tests. We confirm that linguistic and extralinguistic
      factors must be taken into account to explain ambiguous idiom interpretation, and
      we underline the role of the testing modality in the case of pathological
      populations.

PMID- 18618359
TI  - Reliable change and practice effects: outcomes of various indices compared.
AB  - In this article the outcomes of three indices for the assessment of reliable
      change (RCIs) are compared: the null hypothesis method of Chelune, Naugle,
      Luders, Sedlak, and Awad (1993), the regression-based method of McSweeny, Naugle,
      Chelune, and Luders (1993), and a recently proposed adjustment to the latter
      procedure (Maassen, 2003). Simulated data demonstrated the importance of using
      large control samples. The regression-based method proved to be the most lenient
      in designating individuals as reliably changed, resulting in the most correct and
      the most incorrect designations. The adjusted procedure resulted in fewer correct
      designations and the lowest numbers of incorrect designations. Real-world data
      showed the same patterns.

PMID- 18618360
TI  - Treatment of halo nevus with 308-nm excimer laser: a pilot study.

PMID- 18618361
TI  - Efalizumab-associated papular psoriasis: an adverse reaction to efalizumab in
      three cases.
AB  - Efalizumab-associated papular psoriasis is a common adverse event caused by
      efelizumab therapy. This clinical manifestation is characterized by a transient
      popular eruption localized especially on the flexural areas and on the back. We
      report three cases of efalizumab-associated papular psoriasis.

PMID- 18618362
TI  - Dexamethasone cyclophosphamide pulse therapy in systemic lupus erythematosus: a
      case report.
AB  - OBJECTIVE: To put systemic lupus erythematosus (SLE) in remission for a prolonged
      period. METHODS: Dexamethasone cyclophosphamide pulse (DCP) therapy was used in a
      40-year-old female with SLE of 3 years' duration. DCP therapy comprises an
      intravenous infusion of 100 mg dexamethasone in 500 ml of 5% glucose over 1
      1(1/2) hours on 3 consecutive days along with cyclophosphamide 500 mg in the same
      drip on the first day. This was repeated at 4-week intervals till 9 months after
      all the lesions cleared. In between the DCP therapy she was given 50 mg
      cyclophosphamide orally daily. RESULTS: The skin lesions cleared with 11 DCP
      therapies. There was no relapse 24 months after stopping all treatment.
      CONCLUSION: DCP therapy appears to put SLE into prolonged remission.

PMID- 18618363
TI  - Lowering lesional surface pH in acne: a new treatment modality for Herpifix.
AB  - The acid skin surface pH has antimicrobial activities. Increased growth of
      Propionibacterium acnes contributes to the pathogenesis of acne. Therefore, the
      pH of inflammatory acne lesions was determined prior to and after lesional
      acidification employing Herpifix (Courage + Khazaka, Cologne, Germany), a
      microphoretic system. The pH was correlated with the number of acne lesions. A
      total of 30 volunteers with acne vulgaris participated in this crossover study
      applying either Herpifix or a dummy to inflammatory lesions. Prior to treatment,
      the pH of acne lesions was 5.7 +/- 0.2 (mean +/- SD) and 22 lesions (mean +/- 10)
      were counted in an 8 x 8 cm(2) facial surface area. Fifteen volunteers (group A)
      used Herpifix first for 3 weeks and then the dummy, while the other group of 15
      volunteers (group B) used the dummy first and then Herpifix. In group A, the
      lesional surface pH and number of lesions decreased (p < 0.01) initially. When
      the dummy was used over a second 3-week treatment period, the skin surface pH and
      number of acne lesions increased. Findings for group B were vice versa. When both
      groups were compared at the end of the study, a significant difference in pH
      values (p < 0.001) and the number of acne lesions (p < 0.05) was obtained.
      Herpifix may be considered as a new therapeutic option for inflammatory acne.

PMID- 18618365
TI  - The human genome and sport, including epigenetics and athleticogenomics: a brief
      look at a rapidly changing field.
AB  - Since Hugh Montgomery discovered the first of what are now nearly 200 "fitness
      genes", together with rapid advances in human gene therapy, there is now a real
      prospect of the use of genes, genetic elements, and/or cells that have the
      capacity to enhance athletic performance (to paraphrase the World Anti-Doping
      Agency's definition of gene doping). This overview covers the main areas of
      interface between genetics and sport, attempts to provide a context against which
      gene doping may be viewed, and suggests a futuristic legitimate use of genomic
      (and possibly epigenetic) information in sport.

PMID- 18618364
TI  - In vitro antileukemia, antibacterial and antifungal activities of some 3d metal
      complexes: chemical synthesis and structure - activity relationships.
AB  - The present paper describes the synthesis, characterization and in vitro
      biological evaluation screening of different classes (ammoniacates, dioximates,
      carboxylates, semi- and thiosemicarbazidates) of Co(II), Co(III), Cu(II), Ni(II),
      Mn(II), Zn(II) and Fe(III) complexes. Schiff bases were obtained from the
      reaction of some salicyl aldehydes with, respectively, furoylhydrazine,
      benzoylhydrazine, semicarbazide, thiosemicarbazide and S-methylthiosemicarbazide
      to give tridentate ligands containing ONO, ONS or ONN as donor atoms. The
      synthetic metal complexes are of various geometrical and electronic structures,
      thermodynamic and thermal stabilities, and magnetic and conductance properties.
      All complexes, except those of Cu, are octahedral. Some Cu, Co and Mn compounds
      have a dimeric or a polymeric structure. The composition and structure of
      complexes were analysed by elemental analysis, IR and (1)H NMR and (13)C NMR
      spectroscopies, and magnetochemical, thermoanalytical and molar conductance
      measurements. All ligands and metal complexes were tested as inhibitors of human
      leukemia (HL-60) cells growth, and the most potent, the Cu(II) complexes, have
      been also tested for their in vitro antibacterial and antifungal activities.
      Structure-activity relationships were carried out.

PMID- 18618366
TI  - Testing the Finno-Ugrian Suicide Hypothesis: geographic variation of elderly
      suicide rates across Europe.
AB  - The pattern of geographic variation in European suicide rates in the high-risk
      group of individuals aged 65 years and over was investigated, in order to provide
      a further test of the Finno-Ugrian Suicide Hypothesis, i.e. the assumption that
      genetic differences between populations may partially account for spatial
      differences seen in the suicide prevalence. National suicide rates (average of
      1970-2002) of the elderly from 34 European countries were regressed on geographic
      position terms, i.e. capital cities' latitude and longitude, along with
      transformations (e.g. squared latitude) and interaction terms (e.g. latitude
      multiplied with longitude) of these, which statistically modeled various possible
      geographic gradients in the suicide rates. In these regression models, the
      strongest and statistically significant predictor of elderly suicide rates was an
      interaction term of squared latitude multiplied with longitude, indicating that
      suicide rates increased to the northeast. This accounted for 13.8% (total), 20.8%
      (males) and 11.6% (females) of the cross-national variance in elderly suicide
      rates. No further geographic position term accounted for a significant increment
      of further variance in suicide rates over and above this predictor. Controls for
      national quality of living conditions and alcohol consumption rates left these
      results essentially unchanged. Replicating previous evidence based on suicide
      rates of the general population, suicide rates of the elderly show a northeastern
      gradient across Europe. This J-shaped belt of high-suicide-rate countries spans
      from Central Europe (Austria, Hungary and Slovenia) to Northeastern Europe
      (Finland and the Baltic countries). There are early historical and genetic
      communalities among the populations inhabiting this area, but, in terms of
      culture, recent history, political systems and socioeconomic factors, there is
      great diversity between these countries. The current findings thus add to
      cumulated empirical evidence consistent with the Finno-Ugrian Suicide Hypothesis.

PMID- 18618367
TI  - Predicting lifetime mood elevation in primary care patients and psychiatric
      patients.
AB  - Unipolar depression is undoubtedly the most common affective disorder, but
      recently the role of bipolar disorders has become more and more significant. The
      aim of the study was to improve the detection of mood elevations by careful
      anamnestic assessment, especially family history and psychosocial functional
      skills. A sample, screened for depression, of 430 primary care patients and 423
      psychiatric patients aged 18-64 were interviewed in 1991-1992 using the Present
      State Examination. Anamnestic information was obtained by questionnaire and
      interview. Participants were re-contacted in 1998-1999. Experienced lifetime mood
      elevation was assessed in the follow-up study using the main criteria of the ICD
      10 in a telephone interview by three research psychiatrists. Patient's smoking,
      suicidality in the Hamilton Depression Scale (HAM-D), problems in making contact
      with the opposite sex when a teenager, and mental problems in either of the
      parents when the patient was < or = 15 years were associated with experienced
      lifetime mood elevation. Quick and easy questions about smoking and difficulties
      in making contact with the opposite sex may improve the detection of mood
      elevation.

PMID- 18618368
TI  - Comparison of saliva sampling methods for measurement of salivary adiponectin
      levels.
AB  - We measured salivary adiponectin levels in saliva samples collected in two
      different ways and compared the results. Using the Salivette system, we collected
      samples from 30 healthy females into test tubes. Salivary adiponectin levels were
      evaluated using a commercial enzyme immunoassay kit for plasma but with a
      slightly modified method. While there was a significant correlation between
      adiponectin levels in plasma and test-tube saliva (p<0.05), no correlation
      between adiponectin levels in plasma and Salivette-sampled saliva was apparent.
      These findings suggest that test-tube sampling is more reliable than use of the
      Salivette system for measuring salivary adiponectin levels.

PMID- 18618369
TI  - Relationship between red blood cell distribution width and kidney function tests
      in a large cohort of unselected outpatients.
AB  - OBJECTIVE: A strong, independent, association has recently been shown between
      higher red blood cell distribution width (RDW) and the risk of all-cause death
      and cardiovascular events. However, the mechanism(s) underlying this association
      remains unclear. Since impaired kidney function is a well-known risk factor for
      cardiovascular disease, we assessed whether RDW is associated with decreased
      kidney function. MATERIAL AND METHODS: We cross-sectionally assessed results of
      RDW, haemoglobin, main corpuscular volume (MCV) and serum creatinine levels in a
      large cohort of unselected adult outpatients consecutively referred by general
      practitioners for routine medical check-up. Glomerular filtration rate (GFR) was
      estimated using the abbreviated Modification of Diet in Renal Disease (MDRD)
      equation. RESULTS: Cumulative results of RDW, creatinine and other variables were
      retrieved from the database of our Laboratory Information System for 8,585 adult
      outpatients over a 3-year period. When participants were grouped according to RDW
      quartiles, there was a strong, graded, decrease in estimated GFR levels (ranging
      from 87+/-18 to 81+/-32 mL/min/1.73 m(2); p<0.0001). Accordingly, the percentage
      of participants with estimated GFR<60 mL/min/1.73 m(2) increased steadily across
      RDW quartiles (from 5 % to 19 %; p<0.0001). In logistic regression analysis,
      lower estimated GFR strongly predicted higher RDW levels (p<0.0001) independently
      of age, gender, MCV and haemoglobin values. CONCLUSIONS: Our findings suggest
      that there is an inverse, graded, association between RDW and kidney function
      tests in a large cohort of unselected adult outpatients.

PMID- 18618370
TI  - Reduced bone mass and increased bone turnover in postmenopausal women with
      epilepsy using antiepileptic drug monotherapy.
AB  - OBJECTIVES: The aims of this study were to assess the occurrence of osteoporosis
      and fracture rate in Norwegian postmenopausal women with epilepsy using
      antiepileptic drugs (AEDs), and to investigate how AEDs may affect bone health.
      MATERIAL AND METHODS: Twenty-six female patients receiving AED monotherapy and 26
      individually matched healthy controls answered questions about their general
      health, lifestyle and previous fractures. For both groups, bone mineral density
      (BMD) was measured by DEXA, and serum samples were analysed for biochemical bone
      turnover markers and haematological parameters. RESULTS: The patients,
      particularly those treated with enzyme-inducing AEDs, had significantly lower BMD
      than the controls. Additionally, 62 % of the women with epilepsy had osteoporotic
      T-values in one or more regions, compared with 27 % in the control group. There
      was a non-significant tendency towards an increased fracture rate among the
      patients. Markers for bone formation (ALP, bALP, osteocalcin) and bone resorption
      (Crosslaps) were elevated in the patient group compared with the controls.
      CONCLUSIONS: Compared with the healthy controls, we found an increased occurrence
      of osteoporosis, probably due to increased bone turnover, among Norwegian
      postmenopausal women with epilepsy undergoing AED monotherapy, which may render
      these women especially vulnerable to fractures.

PMID- 18618371
TI  - A randomized, double-blind, placebo-controlled clinical trial of the
      effectiveness of the novel serotonin type 3 receptor antagonist ramosetron in
      both male and female Japanese patients with diarrhea-predominant irritable bowel
      syndrome.
AB  - OBJECTIVE: Irritable bowel syndrome is characterized by abdominal discomfort
      and/or pain associated with altered bowel habits. The neurotransmitter serotonin
      and serotonin type 3 receptors that are extensively distributed on enteric
      neurons in the human gastrointestinal tract play a role in increasing the
      sensation of pain and affecting bowel habits in patients with irritable bowel
      syndrome. The aim of this study was to evaluate the efficacy and safety of the
      serotonin type 3 receptor antagonist ramosetron hydrochloride in Japanese
      patients with diarrhea-predominant irritable bowel syndrome. MATERIAL AND
      METHODS: In a double-blind, placebo-controlled, parallel group-comparative study
      with a 1-week run-in period, 539 patients with diarrhea-predominant irritable
      bowel syndrome meeting the Rome II diagnostic criteria received either 5 microg
      ramosetron hydrochloride (n=270) or placebo (n=269) once daily for 12 weeks.
      RESULTS: Forty-seven percent of ramosetron hydrochloride-treated patients were
      monthly responders in the primary end-point, "Patient-reported global assessment
      of relief of irritable bowel syndrome symptoms", compared with 27% for placebos
      (p<0.001). The most frequently reported adverse event in the ramosetron
      hydrochloride-treated group compared with the placebo group was hard stool.
      CONCLUSIONS: Ramosetron hydrochloride 5 microg once daily is effective and well
      tolerated in the treatment of abdominal pain, discomfort and bowel habits in
      patients with diarrhea-predominant irritable bowel syndrome.

PMID- 18618372
TI  - Incidence of enteropathy--associated T-cell lymphoma: a nation-wide study of a
      population-based registry in The Netherlands.
AB  - OBJECTIVE: Enteropathy-associated T-cell lymphomas (EATLs) are T-cell non-Hodgkin
      lymphomas of the small bowel, which are specifically associated with coeliac
      disease (CD). To our knowledge no studies have previously reported on the overall
      incidence of EATLs in the general population. The aim of this study was to
      investigate the incidence of EATL and the demographic characteristics of patients
      with EATL in The Netherlands. MATERIAL AND METHODS: A survey of the nation-wide
      network and registry of histo- and cytopathology reports in The Netherlands
      (PALGA) was performed. We included all T-cell lymphomas detected between January
      2000 and December 2006 that initially presented in the small bowel. Crude and
      world standardized incidence rates were computed as well as gender- and age
      specific incidence rates. Finally, the distribution of characteristics such as
      the localization, the Marsh classification and method of diagnosis are described.
      RESULTS: Clinicopathological data were gathered for 116 cases of EATL. The mean
      age at primary presentation of EATL was 64 years. The crude incidence in the
      total Dutch population was 0.10/100,000 with an incidence of 2.08/100,000 in the
      over 50-year-olds. Age-specific incidences were 1.44/100,000 in the 50-59 years
      age group, 2.92/100,000 in the 60-69 years age group, and 2.53/100,000 in the 70
      79 years age group. There was a significant predominance of males (64%, p=0.004,
      CI 54-72); above the age of 50 the gender-specific incidence was 2.95/100,000 in
      males versus 1.09/100,000 in females. Most EATLs were localized in the proximal
      small intestine and the diagnosis was made by surgical resection in the majority
      of cases. CONCLUSIONS: EATL is a rare disease with an incidence of 0.10 per
      100,000 inhabitants per year, occurring in older age, with a peak incidence in
      the 7th decade. The tumour is mainly localized in the proximal small intestine.
      Although uncomplicated CD is twice as frequent in female patients, EATL is more
      prevalent in males.

PMID- 18618373
TI  - Human metapneumovirus pneumonia in children: results of an Italian study and mini
      review.
AB  - Human metapneumovirus (hMPV) is a newly identified paramyxovirus causing lower
      respiratory tract infections (LRTI). Current knowledge on hMPV is mainly based on
      retrospective studies performed in stored respiratory and serum samples. We found
      15 previous prospective clinical studies on LRTI (11 clinical and 4
      epidemiological studies) that have been reviewed. Our aims were to analyse the
      role of hMPV in community acquired pneumonia (CAP) and the seroconversion rate to
      hMPV in a prospective study in North Italian children. During a 15-month study
      period, 124 children were admitted due to presumptive CAP and, in 116 of them,
      CAP was radiologically confirmed. The aetiology of CAP was assessed by serology
      to 15 microorganisms, including enzyme immunoassay to hMPV. hMPV infection was
      found in 5 children (4.9%), being single in 2 and mixed in 3 cases. The
      seroconversion rate to hMPV increased with age, reaching nearly 100%
      seropositivity rate at school age. In conclusion, hMPV caused 0% to 17.5% of LRTI
      cases in children in the mini-review. The figure was about 5% in the present and
      in the only earlier paediatric CAP study. Thus, hMPV is a real but rare cause of
      paediatric CAP, although seroconversion to hMPV in most children takes place in
      early childhood.

PMID- 18618374
TI  - Roadside ecology and epidemiology of tick-borne diseases.
AB  - When humans, pets and livestock walk along roads, they may encounter questing
      ticks and tick-borne pathogens. A new field of environmental science called road
      ecology can help researchers study the complex epidemiology of tick-borne
      diseases in the unique roadside environment. This paper reviews some of the
      important ways that roads alter the distribution, abundance and behaviour of
      wildlife species that are involved in the enzootic cycles of tick-borne diseases.
      Compared to the surrounding landscape, roadways often constitute a different
      environment and hence there is no assurance that disease risk along roads will be
      the same as in the adjacent landscape, or that disease control measures taken in
      the surrounding landscape will work in the adjacent roadway. Since roadways have
      their own special ecological conditions, are used extensively by the human
      populace and play strategic roles in community security, we believe that roadways
      should be one of the habitats where tick-borne diseases are studied. It is
      amazing that at this late period of human history, epidemiological research along
      such important corridors has been almost completely ignored.

PMID- 18618376
TI  - Congenital bilateral perisylvian syndrome: a case study.
AB  - We report the case of a 14-year-old boy with bilateral congenital perisylvian
      syndrome as evidenced by polymicrogyria in the left and right frontotemporal
      regions, pseudobulbar paresis, seizures, and spastic diplegia. This is the first
      description of comprehensive neuropsychological assessment in a child with this
      syndrome. The results reflect significant impairments in auditory processing and
      independent learning and retention, but relatively preserved cognitive
      performance on interactive tasks involving frequent feedback and redirection. The
      findings are interpreted in the context of the neuropathology of this syndrome,
      with an emphasis on pragmatic implications for rehabilitation.

PMID- 18618377
TI  - Behaviour and gaze analyses during a goal-directed locomotor task.
AB  - The objectives of the current study were: (a) to determine whether perception
      action coupling controlled behaviours when walking through moving doors and (b)
      to determine how vision contributed to this behaviour. Participants (N = 6)
      walked along a 7-m path toward two motor-driven doors, which moved at rates
      ranging between 20 and 40 cm/s. Each door was independently driven such that both
      moved at the same velocity (symmetrical) or at different velocities
      (asymmetrical). The results showed that in both door movement conditions the
      participants controlled their approach velocity by slowing down prior to crossing
      the doors. The decrease in walking velocity produced greater velocity variability
      in the final stages prior to crossing the doors and high success rates. The
      results from the gaze behaviours showed that fixation durations were
      significantly longer when the doors moved asymmetrically, suggesting that the
      visual information from this unpredictable environment took longer to process.
      However, the fixation patterns were similar between the two door movement
      conditions. Regardless of the door movement condition, the participants spent
      about 60% of each trial fixating environmental objects (i.e., left door, right
      door, or aperture). The majority of fixations were directed towards one of the
      doors at the beginning of the trial and then shifted towards the aperture in the
      final phase. The participants were using perception-action coupling to control
      their behaviours in the final phase in order to steer locomotion through the
      aperture.

PMID- 18618378
TI  - [Pitfalls in diagnosis of celiac disease].
AB  - Both serology and histology remain cornerstones in the diagnosis of coeliac
      disease. IgA class antibodies against tissue transglutaminase and endomysium have
      the highest specificity and sensitivity in comparison with other serological
      tests. An IgA deficiency in serum must always be excluded. Antigliadin antibodies
      have, because of their low positive predictive value apart from in early
      childhood, no value as a diagnostic tool in coeliac disease. Intestinal biopsies
      should be evaluated according to the revised Marsh criteria. A discrepancy
      between serology and histology requires a competent evaluation by a
      gastroenterologist and, if necessary, further diagnostic procedures.

PMID- 18618379
TI  - Adjuvant chemotherapy for colon cancer--analysis of treatment costs from the
      perspective of statutory sickness funds.
AB  - OBJECTIVE: The aim of this study was to calculate sickness funds' costs
      associated with the application of three different adjuvant chemotherapy regimens
      for patients with stage III colon cancer treated in different settings
      (inpatient/outpatient) in Germany. METHODS: Standard procedures according to
      national guidelines were defined for inpatient and outpatient diagnostics and
      treatment. Costs associated with the three commonly used standard treatment
      regimens were calculated from the perspective of statutory sickness funds.
      RESULTS: The highest costs are associated with the FOLFOX regimen in the
      outpatient (21530.00 euro) as well as in the inpatient setting (23170.00 euro).
      Of the two 5-FU bolus regimens, the monthly MAYO-Clinic protocol (inpatient
      7070.00 euro vs. outpatient 6610.00 euro) is significantly less expensive than
      the weekly NSABP protocol (17569.00 euro vs. 12200.00 euro). Costs are remarkably
      lower in the outpatient setting as compared to inpatient application of the MAYO
      Clinic protocol or the FOLFOX regimen. In the outpatient setting, medication
      costs are the major cost-driving factor, comprising 82% of the total costs of the
      MAYO-Clinic protocol, 94% of the total costs of the NSABP, and 91% of the total
      costs of FOLFOX-4 regimen. In the inpatient setting, costs for medications are
      less important with regard to total costs (10% MAYO-Clinic, 7% NSABP, 10% FOLFOX
      4), whereas costs for staff and hotel-like services become more important.
      CONCLUSION: From a health insurance perspective, substantial cost savings may be
      realised through the use of established chemotherapy regimens, if most patients
      are treated in the outpatient setting. In the outpatient setting, costs for drug
      prices are the main cost driver, so further savings could be realised for third
      party payers if prices of chemotherapeutic drugs are reduced. For economic
      reasons, patients who are candidates for bolus 5-FU regimens, should not be
      treated according to the NSABP protocol. The MAYO-Clinic protocol is a low cost
      regimen in both settings, but for medical reasons alternative therapies such as
      capecitabine or infusional 5 FU protocols must be preferred in patients unable to
      tolerate the new standard FOLFOX-4.

PMID- 18618380
TI  - [The solid pseudopapillary tumor (SPT)--a rare neoplasm of the pancreas].
AB  - BACKGROUND: In general, the rare SPT is a tumour of low malignancy predominantly
      affecting young women. The outcome after radical resection is favourable. In
      exceptional cases the tumour presents as solid pseudopapillary carcinoma (SPC)
      with typical malignant features and even metastases. Unresectable liver
      metastases can be treated with RFA, TACE or chemotherapy. METHODS: We
      retrospectively reviewed the surgical approach, immunohistochemistry and clinical
      outcome in five female patients (1998--2007). RESULTS: The mean age was 16 years
      (range: 13-47 years). For radical tumour removal a pancreato-duodenectomy (n =
      3), a distal pancreatectomy (n = 1) and an enucleation (n = 1) were performed. We
      encountered a mean tumour diameter of 8 cm (range: 6-15 cm), an angioinvasion
      (3/5) and a lymphatic infiltration (1/5). After 30 to 101 months follow-up four
      patients were free of recurrence. Chemotherapy has resulted in a survival of over
      98 months in a case of SPC with liver metastases. CONCLUSION: SPT is a tumour of
      low malignancy. Radical resection is recommended for long-term recurrence-free
      survival. Chemotherapy may prolong survival in SPC with unresectable metastases.

PMID- 18618381
TI  - [Immune-mediated hemolytic anemia under oxaliplatin].
AB  - The induction of autoimmune hemolysis is a rare side effect of oxaliplatin. A 68
      year-old patient was referred to our hospital because of progedient jaundice and
      exertional dyspnea. One day before she had received the 5th consecutive week of
      treatment of the 8th cycle of a chemotherapy according to FUFOX protocol with
      oxaliplatin and 5-fluorouracil because of metastasized adenocarcinoma of the
      sigma. Laboratory values revealed hemolytic anemia associated with
      thrombocytopenia and neutropenia. In the further clinical course a rapid decline
      of the hemoglobin (hb) level could be observed associated with a significant
      increase of hemolysis parameters. A direct Coombs test was positive consistent
      with oxaliplatin-mediated autoimmune anemia (AIHA) and a pulse therapy with
      steroids was started accompanied by transfusions resulting in a normalization of
      red blood cell and white blood cell counts. Chemotherapy was switched to an
      oxaliplatin-free regimen because of progressive tumor disease and induction of
      immune pancytopenia. Oxaliplatin-induced AIHA requires an immediate diagnosis
      since reexposition results in a more severe hemolysis. The direct Coomb's test
      represents the essential hallmark of the diagnosis.

PMID- 18618382
TI  - A 9-year retained T-tube fragment encased within a stone as a rare cause of
      jaundice.
AB  - Biliary diseases such as cholangitis may cause jaundice and liver damage. Here,
      we report on an unusual cause of jaundice in an 84-year-old man 9 years after
      cholecystectomy. Ultrasound analysis revealed unclear extrahepatic cholestasis
      and subsequent ERCP showed a large biliary stone surrounding a T-tube fragment
      that had remained in the common bile duct for more than 9 years after surgery.
      The tip of the drainage and the stone could be successfully removed using Dormia
      baskets. This case suggests that plastic material accidentally left in the common
      bile duct favours the development of large biliary casts when present over long
      periods of time.

PMID- 18618383
TI  - [Chronic intestinal pseudo-obstruction--review and update 2008].
AB  - The term chronic intestinal pseudo-obstruction describes a syndrome of severly
      altered gastrointestinal motility that clinically resembles mechanical intestinal
      obstruction. The syndrome comprises numerous underlying primary or secondary
      neuropathies of the intrinsic or entrinsic nervous system as well myopathies.
      Almost a third of the patients requires long-term total parenteral nutrition
      (TPN). However, emergency surgery and even small bowel transplantation as an
      ultimate option after failure of TPN may become necessary to evade a vital
      threat. Although our understanding of pathogenesis and therapeutical options is
      still evolving, current knowledge allows a differentiated diagnostic approach,
      classification of the primary and secondary causes and differentiated therapy.

PMID- 18618384
TI  - [Gastroenterological palliative care].
AB  - On consideration of current medical and socio-economical factors, palliative care
      is becoming an increasingly important aspect of modern medicine in Germany. The
      German Society for Digestive and Metabolic Disorders (DGVS) has taken this into
      account by founding the working group "Palliative Gastroenterology". Patients
      with gastrointestinal malignancies or advanced non-malignant liver disease
      represent an important group that benefits from palliative care. Approximately 80
      % of all palliative care patients suffer from gastrointestinal symptoms and
      endoscopic procedures performed by gastroenterologists play an important role in
      relieving symptoms such as obstruction. It is the object of this paper to
      evaluate the role of gastroenterologists in palliative medicine. It will give a
      brief definition, a historical review and the current legal background for
      palliative care in Germany and examine special aspects of ethics, decision making
      and research. Considering the current evidence on palliative endoscopic
      procedures this paper wants to establish the role of the gastroenterologist in
      palliative care far beyond the mere practicalities of endoscopy. The
      gastroenterologist is a crucial element of the interdisciplinary palliative care
      team and a partner to the patient in the process of decision-making. Finally, it
      is demonstrated how palliative care structures can be implemented in the setting
      of a university acute-care hospital.

PMID- 18618386
TI  - Volatiles from leaves and rhizomes of Fragrant Acorus spp. (Acoraceae).
AB  - Three horticultural selections of Acorus gramineus Soland were investigated to
      determine the chemical composition of their leaves and rhizomes. The variety
      'liquorice' was found to contain methylchavicol (49%) which accounts for the
      unusual anisic odor of this variety, while beta-asarone was the main component of
      A. christophii (43%) and 'yodo-no-yuki' (20%). The results are compared with
      calamus oils, and the possible biosynthetic precursors of the main components
      methylchavicol and beta-asarone are considered.

PMID- 18618387
TI  - Flower scents from the Pacific.
AB  - For a long time, exotic scents from the islands of the South Pacific have
      universally been appreciated. Most frequently, fragrant flowers (e.g.,
      frangipani, jasmine sambac, tiare, pua kenikeni) are used locally for ornamental
      purposes such as flower garlands (leis). Despite their powerful and delightful
      fragrance, very few of these flowers have been commercially employed in this part
      of the world for perfume manufacturing. Creative perfumers are nevertheless
      strongly interested to better understand these fragrances and to use them, either
      genuine or artificially reconstituted. Analytical results on the fragrance of
      these flowers are reported, together with some economical considerations.

PMID- 18618388
TI  - Chemistry around pinene and pinane: a facile synthesis of cyclobutanes and
      oxatricyclo-derivative of pinane from cis- and trans-pinanols.
AB  - Alpha-pinene and beta-pinene are abundantly represented in nature; they are
      obtained from renewable sources and are irreplaceable synthons for commercial
      scale production of other terpenes. In a well-known process practiced by
      Millennium Specialty Chemicals (MSC), hydrogenation of pinenes gives cis- and
      trans-pinanes, which are oxidized to hydroperoxides, whose reduction gives cis-
      and trans-pinanols, respectively. Pyrolysis of the pinanols gives linalool.
      Industrial availability of the pinanols makes them attractive objects for further
      synthetic research. We found that, in a very simple process of 'chlorooxidation',
      cis- and trans-pinanols react with hypochloric acid producing a novel
      chloroketone 1-[3-(2-chloroethyl)-2,2-dimethylcyclobutyl]ethanone and a tricyclic
      ether 6,9-dimethyl-7-oxatricyclo[4.3.0.0(3,9)]nonane, respectively. Both
      compounds offer new broad synthetic opportunities, providing access to numerous
      dimethylcyclobutane derivatives and to C(9)-functionalized pinenes and pinanes.
      The chlorooxidation reaction was also extended to other terpene alcohols such as
      dihydroplinol, tetrahydromyrcenol, and tetrahydrolinalool. This review, based on
      a presentation at the RSC/SCI conference Flavours & Fragrances 2007 in London,
      September 24-26, 2007, will touch on environmental issues related to pinenes,
      give a brief overview of the existing pinene-based technologies, and discuss the
      new experimental results.

PMID- 18618389
TI  - Odorant design based on the carbon/silicon switch strategy.
AB  - Silicon chemistry has been demonstrated to be a novel source of chemical
      diversity in odorant design. The carbon/silicon switch strategy, i.e., sila
      replacement in known odorants, is one of the methods currently used for the
      development of silicon-based odorants. Examples resulting from this strategy are
      sila-coranol, sila-dimetol, sila-linalool, sila-muguetalcohol, sila-majantol,
      sila-hydratropyl acetate, sila-bourgeonal, sila-lilial, disila-versalide, and
      disila-okoumal.

PMID- 18618390
TI  - Synthetic applications of enantioselective protonation and case study for (S)
      alpha-damascone.
AB  - Among the fragrance compounds synthesized by enantioselective protonation, (S)
      alpha-damascone, (R)-muscone, and (S,S)-Vulcanolide are the most prominent ones.
      (S)-alpha-damascone has been prepared by four different procedures: from the
      magnesium enolate, from the lithium enolate, from the enol, and from the
      corresponding thiol ester. We now present a new, industrially viable protocol for
      the addition of allyl magnesium chloride to the 'cyclogeranoketene' by a Barbier
      reaction, followed by protonation of the ensuing magnesium enolate by an
      aggregate formed from (-)-N-isopropylephedrine, lithium isopropylate, and acetic
      acid, furnishing (S)-alpha-damascone in 91% yield and with 71% ee.

PMID- 18618391
TI  - Cetalox and analogues: synthesis via acid-mediated polyene cyclizations.
AB  - Using a novel, acid-mediated cyclization methodology, a direct access to Cetalox
      ((+/-)-1; a commercially important ambergris-type odorant) and various
      structurally related didehydro (i.e., 19, 26, and 30) and tetradehydro (i.e., 28
      and 37/38) analogues is described. Treatment of either (E,E)-14 or (E)-15 with an
      excess of FSO(3)H in 2-nitropropane at -90 degrees stereospecifically afforded
      (+/-)-1 in 40 and 42% yield, respectively. Under similar conditions, cyclization
      of (E)-18 or 20 furnished 19 in 60 and 64% yield, respectively. Analogously,
      using an excess of ClSO(3)H in CH(2)Cl(2) at -80 degrees, 26 is formed with high
      stereoselectivity by cyclization of either (E)-24 or (Z)-25 (52 and 31% yield,
      resp.); in the same manner, 28 was prepared from 27 (22% yield). The same
      principle was applied to the synthesis of racemic Superambrox (30), via
      cyclization of 35, but only with poor selectivity (22%) and low yield (7%).
      Another approach via cyclization of (E)-40 under solvolysis conditions (excess
      TFA in CH(2)Cl(2) at -10 degrees) gave a higher yield (15%) with improved
      selectivity (43%). Finally, cyclization of 34 (1:1 diastereoisomer mixture)
      afforded 37/38 (10:1) in 27% yield. The qualitative organoleptic properties of
      19, 26, 28, 30, and 37/38 (10:1) are briefly discussed.

PMID- 18618392
TI  - Marine fragrance chemistry.
AB  - The main marine message in perfumery is projected by Calone 1951 (7-methyl-2H-1,5
      benzodioxepin-3(4H)-one). Kraft (Givaudan) and Gaudin (Firmenich) further
      maximized the marine fragrance molecular membership by extending the carbon chain
      of the 7-Me group. Our research targeted the polar group of the benzodioxepinone
      parent compound to investigate how this region of molecular makeup resonates with
      the dominant marine fragrance of the Calone 1951 structure. The olfactory
      evaluation of analogues prepared by chemical modification or removal of the CO
      group resulted in the introduction of aldehydic, sweet and floral-fruity notes
      with a diluted/diminished potency of the marine odor. To further analyze the
      olfactory properties of benzodioxepinones containing a diverse range of aromatic
      ring substituents, a novel synthesis route was developed. We found that a 7-alkyl
      group in Calone 1951 was essential for the maintenance of the significant marine
      odor characteristic, and our studies support the concept that the odorant
      structure occupying the hydrophobic binding pocket adjacent to the aromatic ring
      binding site of the olfactory receptor is pivotal in the design and discovery of
      more potent and characteristic marine fragrances. How the structure of
      benzodioxepinones connects to marine sea-breeze fragrances is our continuing
      challenging research focus at the chemistry-biology interface.

PMID- 18618393
TI  - Enantioselective synthesis and olfactory evaluation of 13-alkyl-substituted alpha
      ionones.
AB  - To study the influence of the steric bulk of the substituents at C(5) on the
      olfactory characteristics of alpha-ionone, the (S)-antipodes of compounds 8-10
      were synthesized starting from (S)-alpha-cyclogeraniol (14a). The latter was
      available in useful preparative yield with 95% ee by enantioselective lipase-PS
      mediated acetylation of the racemic mixture. Key step in the conversion of 14a to
      8-10 was an S(N)2'-type reaction of an organocuprate on the allylic phosphate 20,
      which appears to be a general method for the introduction of an alkyl substituent
      at the cyclohexene C=C bond of ionones. Olfactory evaluation showed that,
      compared to the parent (S)-alpha-ionone (1), the odor strength and fragrance
      facets of the three analogues 8-10 are significantly influenced by the bulkiness
      of the substituent at C(13), giving further evidence that hydrophobic
      interactions of this group play a significant role in the chemoreception of
      ionones. In particular, the odor of the ethyl derivative 8 was found to be
      significantly stronger than that of the parent (S)-alpha-ionone (1).

PMID- 18618394
TI  - Homogeneous asymmetric catalysis in fragrance chemistry.
AB  - Opposite enantiomers of a chiral fragrance may exhibit different olfactory
      activities making a synthesis in high enantiomeric purity commercially and
      scientifically interesting. Accordingly, the asymmetric synthesis of four chiral
      odorants, Fixolide, Phenoxanol, Citralis, and Citralis Nitrile, has been
      investigated with the aim to develop practically feasible processes. In the
      devised synthetic schemes, the key step that leads to the formation of the
      stereogenic center is the homogeneous asymmetric hydrogenation of a prochiral
      olefin. By an appropriate choice of the catalyst and the reaction conditions,
      Phenoxanol, Citralis, and Citralis Nitrile were obtained in high enantiomeric
      purity, and odor profiles of the single enantiomers were determined.

PMID- 18618395
TI  - Lewis super-acid catalyzed cyclizations: a new route to fragrance compounds.
AB  - This review deals with the application of Lewis super acids such as Al(III),
      In(III), and Sn(IV) triflates and triflimidates as catalysts in the synthesis of
      fragrance materials. Novel catalytic reactions involving C-C and C-heteroatom
      bond-forming reactions, as well as cycloisomerization processes are presented. In
      particular, Sn(IV) and Al(III) triflates were employed as catalysts in the
      selective cyclization of unsaturated alcohols to cyclic ethers, as well as in the
      cyclization of unsaturated carboxylic acids to lactones. The addition of thiols
      and thioacids to non-activated olefins, both in intra- and intermolecular
      versions, was efficiently catalyzed by In(III) derivatives. Sn(IV) Triflimidates
      catalyzed the cycloisomerization of highly substituted 1,6-dienes to gem-dimethyl
      substituted cyclohexanes bearing an isopropylidene substituent. The
      hydroformylation of these unsaturated substrates, catalyzed by a Rh(I) complex
      with a bulky phosphite ligand, selectively afforded the corresponding linear
      aldehydes. The olfactory evaluation of selected heterocycles, carbocycles, and
      aldehydes synthesized is also discussed.

PMID- 18618396
TI  - Synthesis of l-muscone by asymmetric methylation via enol esters.
AB  - An effective synthetic route of l-muscone (1) by asymmetric methylation, followed
      by enolate-trapping to generate enol esters as intermediates, was described.
      Interestingly, the enol esters can be used as substrates for enzymatic optical
      resolution to improve optical purity. Additionally, several excellent new chiral
      ligands were discovered for asymmetric methylation of (E)-cyclopentadec-2-enone
      to produce l-muscone with high optical purity.

PMID- 18618397
TI  - The search for innovative fragrant molecules.
AB  - An overview of the recent research subjects in the perfumery field and, more
      precisely the synthesis of novel compounds for the hesperidic family of odorants,
      is presented. The new derivatives possess very different structures;
      nevertheless, they all share an aldehydic odor, but with diverse nuances, which
      make them all attractive for different purposes.

PMID- 18618398
TI  - New norbornyl derivatives as woody fragrant materials.
AB  - The optimization of a Diels-Alder reaction to prepare a novel ketone bearing a
      2,3-dimethylnorbornyl group is presented together with the structure elucidation
      of the isomers. Employing this new ketone as starting material, derivatives with
      new woody odor notes as well as attempts to obtain ambery-musky odorants are
      reported.

PMID- 18618399
TI  - Enzyme-triggered and self-cleaving fragrant alcohol precursors.
AB  - The high volatility and water solubility of many natural perfumery alcohols leads
      to their rapid loss in fabric-care and personal-care applications. A dramatically
      enhanced substantivity is achieved by the use of fragrance precursors as
      controlled-release systems. In the first part of this article, we present multi
      odorant precursors, in which the enzymatic cleavage of esters or carbonates of
      fragrant alcohols triggers subsequent steps leading to the release of fragrant
      ketones, lactones, and additional fragrant alcohols. In the second part, a study
      on oligocarbonates of fragrant alcohols is presented. Therein, the outstanding
      enzyme-independent performance of gluconolactone oligocarbonate 27 for the long
      lasting release of (Z)-hex-3-en-1-ol is highlighted. We show that these
      polyfunctional compounds undergo complex rearrangements and intramolecular
      substitution reactions which lead to the observed release kinetics.

PMID- 18618400
TI  - A smelling trip into the past: the influence of synthetic materials on the
      history of perfumery.
AB  - Contemporary perfumery has its roots in the work of the past, and many of the
      perfumes from this time have long since disappeared. What follows is a short
      account of some of the most famous perfumes from the past which have been
      inspired by the novel synthetic materials of the time. These important creations
      include, 'Fougere Royale' by Houbigant (1884) containing coumarin (1), 'Jicky' by
      Guerlain (1889) containing vanillin (2) and linalool (3), 'Vera Violetta' by
      Roger & Gallet (1892) containing alpha- and beta-ionone (4 and 5, resp.), 'Trefle
      Incarnat' by Piver (1898) containing isoamyl salicylate (6), 'La Rose
      Jacqueminot' of Coty (1904) containing Rhodinol (7), 'Apres l'Ondee' by Guerlain
      (1906) containing para-anisaldehyde (8), 'Quelques Fleurs' by Houbigant (1912)
      containing hydroxycitronellal (9), 'N degrees 5' by Chanel (1921) containing the
      aldehydes C-10 (10), C-110 (11), and C-12 (12), 'Nuit De Noel' by Caron (1922)
      containing 6-isobutylquinoline (14), and 'Femme' by Rochas (1944) containing the
      so-called 'aldehyde C-14' (15, gamma-undecalactone). The Osmotheque, the
      International Conservatory of Perfumes, was launched in 1990 and is regarded as a
      primary source of knowledge for the history of perfumery. Its vocation is to
      compile an amazing collection of 1700 perfumes (400 of them almost forgotten
      fragrances)--jewels of perfumery.

PMID- 18618401
TI  - 'Escentric' molecules.
AB  - Can a fragrance be revolutionary? In this commentary, the creation of two
      unusual, extravagant fine fragrances, 'escentric01' and 'molecule01', is
      described. In response to the fantasy components found in release notes of many
      recent perfume launches, both center around a single real fragrance raw material,
      the transparent woody aroma chemical 'Iso E Super' (1+2). The perfume
      'escentric01' contains 65% of it, accompanied by Trisamber (3), red pepper, lime
      oil, incense and musks, while 'molecule01' consists exclusively of 'Iso E Super'
      (1+2). The elegant woody note lives here its own eccentric life--the revolution
      starts.

PMID- 18618402
TI  - From virgin education to real education.
AB  - The now famous virgin headspace experiment from late Braja D. Mookherjee and
      Subha Patel, and its use in the creation of scent 'Virgin No 1' by Christophe
      Laudamiel and Christoph Hornetz for the novel by Patrick Suskind, and the movie
      by Tom Tykwer 'Perfume--The Story of a Murderer' (Constantin Film-Thierry Mugler
      Parfums-IFF, 2006) is discussed. Another fragrance from the luxury coffret,
      'Salon Rouge', is described as well, illustrating how molecules and natural
      ingredients can be utilized, not only to create innovative or artistic fragrance
      compositions, but also to provide fundamental consumer education, improving the
      public image both of Chemistry and Perfumery.

PMID- 18618403
TI  - Instrumental and sensory approaches for the characterization of compounds
      responsible for wine aroma.
AB  - More than 800 aromatic compounds have been identified in wine, some of them at
      the ng/l level. Wine, therefore, constitutes a very complex matrix, from which it
      is difficult to isolate a specific aroma character. Gas chromatography
      olfactometry (GC-O) applied to wine extracts is used to characterize odor-active
      zones that are often treated in a hierarchical way by Aroma Extract Dilution
      Analysis (AEDA). The aromatic impact of the volatiles is evaluated, generally by
      determining perception thresholds. This methodology has provided convincing
      results concerning wine flavors, but it does have its limitations. For instance,
      data on beta-damascenone have demonstrated that these methods could reach their
      limits for this volatile, in particular, because of the non-quantitative
      representation of aroma extracts of wines, and because of the difficulty to
      accurately determine the perception threshold in wines for a compound already
      present. For beta-damascenone, we have shown that its very low detection
      threshold with GC-O, its wide range, and its dependence on the composition of the
      medium resulted in overestimating its direct impact on the aroma of wine. Another
      way to facilitate the characterization of aromatic compounds was, therefore,
      investigated. High-Performance Liquid Chromatography (HPLC) methods were
      developed for the analysis of wine extracts. From an aromatic extract, 25
      fractions with various flavors were thus obtained, and reverse-phase methodology
      was used for the selection and characterization of red- and black-fruit aromas in
      red wines.

PMID- 18618404
TI  - Taste-active compounds in a traditional Italian food: 'lampascioni'.
AB  - Nature is a rich source of taste-active compounds, in particular of plant origin,
      many of which have unusual tastes. Many of these are found in traditional food,
      where spontaneous plants are used as ingredients. Some taste-active compounds
      were identified in the bulbs of Muscari comosum, a spontaneous plant belonging to
      the family of the Liliaceae, very common in the Mediterranean area, and used in
      traditional gastronomy (called 'lampascioni' in South Italy). The bulbs were
      extracted with a series of solvents of different polarity. The different
      fractions were submitted to a preliminary sensory evaluation, and the most
      interesting ones, characterized by a strong bitter taste and some chemestetic
      properties, were submitted to further purification and structural analysis. From
      the ethereal extract, several 3-benzyl-4-chromanones and one stilbene derivative
      were isolated. Pure compounds were examined for their taste activity by means of
      sensory evaluation, and proved to be responsible for the characteristic taste of
      this food. Some of these compounds have been synthesized de novo to confirm their
      structure.

PMID- 18618405
TI  - High-impact sulfur compounds: constitutional and configurational assignment of
      sulfur-containing heterocycles.
AB  - To unambiguously identify their structures and to evaluate their organoleptic
      properties, several constitutional und configurational isomers of dialkyl
      tetrathianes and dialkyl-pentathiepanes were synthesized by two different
      synthetic protocols, and separated by preparative gas chromatography. Raman and
      NMR spectroscopy were used to differentiate between the constitutional 3,6
      dialkyl-1,2,4,5-tetrathiane and the 4,6-dialkyl-1,2,3,5-tetrathiane isomers.
      Furthermore, cis- and trans-isomers of 3,6-dialkyl-1,2,4,5-tetrathianes were
      distinguished by temperature-dependent NMR experiments. Static, quantum-chemical
      simulations of the NMR spectra for these cis- and trans-isomers were calculated
      in the gas layer in order to confirm our experimental assignments. In addition,
      the assignment of 4,7-alkyl-1,2,3,5,6-pentathiepanes were deducted from their
      Raman spectra. Dialkyl-tetrathianes and dialkyl-pentathiepanes are interesting
      components to be used in flavor applications due to their unique olfactory impact
      and facets.

PMID- 18618407
TI  - Human olfactory receptor families and their odorants.
AB  - The human nose detects volatile chemical stimuli by at least three different
      receptor families: odorant receptors, trace amine-associated receptors, and
      vomeronasal type-1 receptors. As G protein-coupled receptors, all of the few
      functionally characterized olfactory receptors share major functional features:
      when expressed in heterologous cell systems, they 1) respond to odorants of
      certain chemical groups, e.g., amines, aliphatic carboxylic acids or aldehydes,
      floral or fruity odorants, including certain key-food odorants, and putative
      pheromones, and 2) transduce their signals to intracellular cAMP signaling.
      However, little is known yet about specific differences in the functional
      designation of the three olfactory receptor families. Recently, two heterologous
      cell systems expressing olfactory signaling molecules have been developed.
      Different screening strategies will shed light on the yet sparsely available
      odorant specificity profiles and structure-function relationships of olfactory
      receptors, as well as the structure-activity relationships of their odorants.

PMID- 18618408
TI  - Retronasal perception of odors.
AB  - Odors often produce different sensations when presented in front of the nose or
      intraorally, when eaten. It is a long-standing question whether these differences
      in sensations are due, for example, to the additional mechanical sensations
      elicited by the food in the mouth or additional odor release during mastication.
      To study this phenomenon in detail, a stimulation technique has been developed
      that allows controlled ortho- or retronasal presentation of odorous stimuli.
      Results from psychophysical, electrophysiological, and imaging studies suggest
      that there are clear differences in the perception of ortho- and retronasal
      stimuli. This 'duality of the sense of smell' is also observed in a clinical
      context where some patients exhibit good retronasal olfactory function with
      little or no orthonasal function left, and vice versa. The differences between
      ortho- and retronasal perception of odors are thought to be, at least partly, due
      to absorption of odors to the olfactory epithelium, which appears to differ in
      relation to the direction of the airflow across the olfactory epithelium.

PMID- 18618409
TI  - Odorant-receptor interactions and odor percept: a chemical perspective.
AB  - Receptor-ligand interaction models are generally based on a 'lock and key'
      concept. How far this holds true for olfactory receptors and odor molecules is
      currently uncertain. Here, we have investigated the response of a human olfactory
      receptor, OR1D2, to a broad array of odorants and found that there is no simple,
      direct correlation between a molecule's ability to activate this receptor and the
      odor impression elicited in the brain. In a parallel study on specific anosmia,
      we have found no evidence for odor-specific anosmia to either musk or amber, but
      rather to specific molecules within these categories. Cluster analysis confirmed
      that there is no simple correlation between molecular structure and impaired
      perception in either odor type. There are some differences in patterns of
      impairment between the two odor types and some evidence to suggest that subjects
      with specific anosmia to a given substance can identify its presence in a
      mixture. Taken together, our results show that simplistic 'lock and key' models
      of olfaction based on a concept of odor-quality-tuned receptors are inadequate,
      irrespective of the nature of the lock-key interaction. Receptor activation is
      only one step in a long chain of events leading from inhalation of odorants to
      perception of odor in the higher brain, and, therefore, although structure-odor
      correlations are useful tools for the design of novel odorants, caution should be
      exercised when extrapolating them to models of olfactory perception. Those
      seeking to understand the odorant-receptor interaction should use receptor
      activation rather than odor as input data.

PMID- 18618410
TI  - Recent developments in the chemistry of sandalwood odorants.
AB  - Natural sandalwood oil, a unique and valuable ingredient in fine perfumery, has
      been the focus of scientific interest for many years. Due to its scarcity and its
      high price, the search for novel synthetic raw materials imitating the
      characteristic odor profile of sandalwood oil is as challenging as ever. In this
      context, the preparation of the novel sandalwood odorants 26, 33, and 39 will be
      discussed, including their sensory properties and structure-odor relationship.

PMID- 18618411
TI  - New oxa-bridged macrocycles.
AB  - In creating new aroma molecules, the fragrance chemist can make use of several
      tools: receptor or combinatorial research as well as lead structure optimization
      of existing chemicals or substances from the natural pool. Sometimes, it is also
      possible to discover new structures via another way: the careful analysis of
      existing products and their production processes. In analyzing the production
      process of 1-oxacyclohexadecan-2-one (6), we identified at least two new oxa
      bridged macrocyclic molecules. In continuation, these results inspired us to
      synthesize and evaluate more representatives with similar structures. In this
      contribution, presented at the RSC/SCI conference 'flavours & fragrances 2007' in
      London, September 24-26, 2007, the synthesis and olfactory properties of several
      new oxa-bridged macrocycles will be introduced and discussed.

PMID- 18618412
TI  - Umbilical venous blood flow measurement: accuracy and reproducibility.
AB  - Umbilical venous blood flow could be considered a direct and physiological
      measurement of vascular placental function, representing the quantity of oxygen
      and nutrients reaching the fetus. The advent of high-technology ultrasound and
      pulsed Doppler has overcome some of the limitations of early studies. Indeed,
      Doppler measurement of umbilical venous blood flow has been found to be accurate
      when compared with several gold standards for in-vivo flow calculation.
      Nevertheless, small errors in volume flow components, the vessel area and the
      mean velocity, result in large errors in the calculation of volume flow.
      Therefore, technique standardization is of paramount importance. Validation
      studies in animal models have demonstrated accurate venous blood flow
      measurements by estimating the vessel's cross-sectional area from perpendicular
      views of longitudinal sections of free-floating portions of the cord. On the
      other hand, estimation of the mean velocity from the maximum velocity, rather
      than using the intensity-weighted mean velocity, is less software-dependent and
      more clearly defined, yielding estimates with more predictable and systematic
      errors. By adhering to stringent methodological recommendations, umbilical venous
      blood flow calculation has moderate to good intra- and interobserver
      reproducibility. Having been found to be accurate and reproducible, further
      studies are required to establish the clinical value of umbilical vein flow
      measurement.

PMID- 18618414
TI  - Bayesian Markov switching models for the early detection of influenza epidemics.
AB  - The early detection of outbreaks of diseases is one of the most challenging
      objectives of epidemiological surveillance systems. In this paper, a Markov
      switching model is introduced to determine the epidemic and non-epidemic periods
      from influenza surveillance data: the process of differenced incidence rates is
      modelled either with a first-order autoregressive process or with a Gaussian
      white-noise process depending on whether the system is in an epidemic or in a non
      epidemic phase. The transition between phases of the disease is modelled as a
      Markovian process. Bayesian inference is carried out on the former model to
      detect influenza epidemics at the very moment of their onset. Moreover, the
      proposal provides the probability of being in an epidemic state at any given
      moment. In order to validate the methodology, a comparison of its performance
      with other alternatives has been made using influenza illness data obtained from
      the Sanitary Sentinel Network of the Comunitat Valenciana, one of the 17
      autonomous regions in Spain.

PMID- 18618413
TI  - Analysis of familial aggregation studies with complex ascertainment schemes.
AB  - Familial aggregation studies are a common first step in the identification of
      genetic determinants of disease. If aggregation is found, more refined genetic
      studies may be undertaken. Complex ascertainment schemes are frequently employed
      to ensure that the sample contains a sufficient number of families with multiple
      affected members, as required to detect aggregation. For example, an eligibility
      criterion for a family might be that both the mother and daughter have disease.
      Adjustments must be made for ascertainment to avoid bias. We propose adjusting
      for complex ascertainment schemes through a joint model for the outcomes of
      disease and ascertainment. This approach improves upon previous simplifying
      assumptions regarding the ascertainment process.

PMID- 18618415
TI  - Compatible simultaneous lower confidence bounds for the Holm procedure and other
      Bonferroni-based closed tests.
AB  - We consider the problem of simultaneously testing multiple one-sided null
      hypotheses. Single-step procedures, such as the Bonferroni test, are
      characterized by the fact that the rejection or non-rejection of a null
      hypothesis does not take the decision for any other hypothesis into account. For
      stepwise test procedures, such as the Holm procedure, the rejection or non
      rejection of a null hypothesis may depend on the decision of other hypotheses. It
      is well known that stepwise test procedures are by construction more powerful
      than their single-step counterparts. This power advantage, however, comes only at
      the cost of increased difficulties in constructing compatible simultaneous
      confidence intervals for the parameters of interest. For example, such
      simultaneous confidence intervals are easily obtained for the Bonferroni method,
      but surprisingly hard to derive for the Holm procedure. In this paper, we discuss
      the inherent problems and show that ad hoc solutions used in practice typically
      do not control the pre-specified simultaneous confidence level. Instead, we
      derive simultaneous confidence intervals that are compatible with a certain class
      of closed test procedures using weighted Bonferroni tests for each intersection
      hypothesis. The class of multiple test procedures covered in this paper includes
      gatekeeping procedures based on Bonferroni adjustments, fixed sequence
      procedures, the simple weighted or unweighted Bonferroni procedure by Holm and
      the fallback procedure. We illustrate the results with a numerical example.

PMID- 18618416
TI  - Analysis of longitudinal data to evaluate a policy change.
AB  - Longitudinal data analysis methods are powerful tools for exploring scientific
      questions regarding change and are well suited to evaluate the impact of a new
      policy. However, there are challenging aspects of policy change data that require
      consideration, such as defining comparison groups, separating the effect of time
      from that of the policy, and accounting for heterogeneity in the policy effect.
      We compare currently available methods to evaluate a policy change and illustrate
      issues specific to a policy change analysis via a case study of laws that
      eliminate gun-use restrictions (shall-issue laws) and firearm-related homicide.
      We obtain homicide rate ratios estimating the effect of enacting a shall-issue
      law, which vary between 0.903 and 1.101. We conclude that in a policy change
      analysis it is essential to select a mean model that most accurately
      characterizes the anticipated effect of the policy intervention, thoroughly model
      temporal trends, and select methods that accommodate unit-specific policy
      effects. We also conclude that several longitudinal data analysis methods are
      useful to evaluate a policy change, but not all may be appropriate in certain
      contexts. Analysts must carefully decide which methods are appropriate for their
      application and must be aware of the differences between methods to select a
      procedure that generates valid inference.

PMID- 18618417
TI  - Development of adenovirus immobilization strategies for in situ gene therapy.
AB  - BACKGROUND: Regenerative gene therapy using viral vectors enables transduced
      cells to express bioactive factors in vivo. Viral delivery with spatial control
      can enhance transduction efficiency and may limit systemic infection.
      Consequently, we tethered biotinylated adenovirus via interactions with avidin on
      chitosan surfaces to gain robust control for in situ transduction. METHODS:
      Avidin was either directly conjugated to chitosan (virus-biotin-avidin-material;
      VBAM) or indirectly docked on biotinylated chitosan surfaces (virus-biotin-avidin
      biotin-material; VBABM) to tether biotinylated adenovirus. Enzyme-linked
      immunosorbent assay (ELISA) and spectroscopic analysis were performed to
      demonstrate the binding profiles. Biotin-alkaline phosphatase and biotinylated
      adenovirus were used as different sized particles to evaluate binding
      efficiencies and were compared by the Sips isotherm adsorption method. Scanning
      electron microscopy (SEM) examination illustrated virus distribution, and the
      transduction efficiency was determined by in vitro cell transduction. RESULTS:
      ELISA and spectroscopic analysis both demonstrated that the VBAM system led to
      multilayer avidin formation on biomaterial surfaces, whereas VBABM formed a
      monolayer of avidin. Sips isotherm adsorption indicated that the VBAM method
      increased heterogeneity and steric hindrance of binding sites. By contrast, the
      VBABM method docked avidin on chitosan surfaces and orientated the binding sites
      to facilitate ligand binding. In addition, SEM images illustrated that the VBABM
      method led to more even viral distribution. In vitro cell infection experiments
      also demonstrated that the VBABM system enhanced virus immobilization and thus
      improved cell transduction efficiency over the VBAM system. CONCLUSIONS: The
      VBABM strategy is a superior method for in situ transduction from biomaterials.
      This strategy could be adapted for use with a variety of biomaterials as well as
      viral vectors, and thus may be an alternative method for in vivo regenerative
      gene therapy.

PMID- 18618418
TI  - Struma ovarii associated with hyperthyroidism, elevated CA 125 and pseudo-Meigs
      syndrome may mimic advanced ovarian cancer.

PMID- 18618419
TI  - Maximum likelihood estimation of correction for dilution bias in simple linear
      regression using replicates from subjects with extreme first measurements.
AB  - The least-squares estimator of the slope in a simple linear regression model is
      biased towards zero when the predictor is measured with random error. A corrected
      slope may be estimated by adding data from a reliability study, which comprises a
      subset of subjects from the main study. The precision of this corrected slope
      depends on the design of the reliability study and estimator choice. Previous
      work has assumed that the reliability study constitutes a random sample from the
      main study. A more efficient design is to use subjects with extreme values on
      their first measurement. Previously, we published a variance formula for the
      corrected slope, when the correction factor is the slope in the regression of the
      second measurement on the first. In this paper we show that both designs improve
      by maximum likelihood estimation (MLE). The precision gain is explained by the
      inclusion of data from all subjects for estimation of the predictor's variance
      and by the use of the second measurement for estimation of the covariance between
      response and predictor. The gain of MLE enhances with stronger true relationship
      between response and predictor and with lower precision in the predictor
      measurements. We present a real data example on the relationship between fasting
      insulin, a surrogate marker, and true insulin sensitivity measured by a gold
      standard euglycaemic insulin clamp, and simulations, where the behavior of
      profile-likelihood-based confidence intervals is examined. MLE was shown to be a
      robust estimator for non-normal distributions and efficient for small sample
      situations.

PMID- 18618420
TI  - The structure of S100A11 fragment explains a local structural change induced by
      phosphorylation.
AB  - S100A11 protein is a member of the S100 family containing two EF-hand motifs. It
      undergoes phosphorylation on residue T10 after cell stimulation such as an
      increase in Ca(2+) concentration. Phosphorylated S100A11 can be recognized by its
      target protein, nucleolin. Although S100A11 is initially expressed in the
      cytoplasm, it is transported to the nucleus by the action of nucleolin. In the
      nucleus, S100A11 suppresses the growth of keratinocytes through p21(CIP1/WAF1)
      activation and induces cell differentiation. Interestingly, the N-terminal
      fragment of S100A11 has the same activity as the full-length protein; i.e. it is
      phosphorylated in vivo and binds to nucleolin. In addition, this fragment leads
      to the arrest of cultured keratinocyte growth. We examined the solution structure
      of this fragment peptide and explored its structural properties before and after
      phosphorylation. In a trifluoroethanol solution, the peptide adopts the alpha
      helical structure just as the corresponding region of the full-length S100A11.
      Phosphorylation induces a disruption of the N-capping conformation of the alpha
      helix, and has a tendency to perturb its surrounding structure. Therefore, the
      phosphorylated threonine lies in the N-terminal edge of the alpha-helix. This
      local structural change can reasonably explain why the phosphorylation of a
      residue that is initially buried in the interior of protein allows it to be
      recognized by the binding partner.

PMID- 18618421
TI  - Multi-state analysis of cognitive ability data: a piecewise-constant model and a
      Weibull model.
AB  - Longitudinal data can be used to estimate transition intensities between healthy
      and unhealthy states prior to death. When health is defined with respect to
      cognitive ability during old age, the trajectory of performance is either static
      or downward. An illness-death model is presented where the intensity of a
      transition is allowed to change over time by using a piecewise-constant model or
      by using a Weibull model. Observed improvement of cognitive ability is modelled
      as misclassification. The methodology is extended to estimate life expectancy
      with and without cognitive impairment. The measurement of cognitive ability is
      important as it is an important predictor of future need for care. The models can
      help to understand how cognitive decline develops over time and which factors
      play a role. The methods are illustrated using data from the Medical Research
      Council Cognitive Function and Ageing Study in the U.K. (1991-2005).

PMID- 18618423
TI  - A complementary La/SSB epitope anchored to Sequential Oligopeptide Carrier
      regulates the anti-La/SSB response in immunized animals.
AB  - Complementary peptide epitopes, derived from complementary RNA sequences, have
      been used for suppressing the autoimmune response in experimental autoimmune
      diseases as myasthenia gravis, allergic neuritis and allergic encephalomyelitis.
      Aiming at contributing to the development of a tool that could regulate the
      autoantibody production against La/SSB, which is the main target of
      autoantibodies in Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE),
      the complementary epitope, cpep349-364, of the minor T/major B cell epitope of
      La/SSB, pep349-364, was utilized for the induction of neutralizing anti-cpep349
      364 antibodies in rabbit immunizations. Complementary peptides were coupled to an
      artificial carrier, developed in our laboratory, in order to enhance the
      complementary potency of cpep349-364 and its counterpart. This carrier, named
      Sequential Oligopeptide Carrier, SOC(n), formed by the repeating tripeptide Lys
      Aib-Gly, adopts helical conformation, which allows the anchored peptide epitopes
      to preserve their initial reactivity such as molecular recognition,
      antigenicity/immunogenicity. Our study provides proof of evidence of specific
      interactions between idiotypic (Id)/anti-idiotypic (anti-Id) antibodies generated
      in immunized animals by the sense epitope (conjugate I) of La/SSB and its
      complementary counterpart (conjugate II). It was also demonstrated that the
      Id/anti-Id association is specifically disrupted by adding either the sense
      epitope (conjugate I) or its complementary counterpart (conjugate II). A mutual
      neutralization of Id/anti-Id antibodies was observed in vivo, which implies that
      generation of anti-Id antibodies by immunization with the complementary La/SSB
      epitope could scavenge the anti-La/SSB response.

PMID- 18618422
TI  - A survey of the likelihood approach to bioequivalence trials.
AB  - Bioequivalence (BE) trials are abbreviated clinical trials whereby a generic drug
      or new formulation is evaluated to determine if it is 'equivalent' to a
      corresponding previously approved brand-name drug or formulation. In this paper,
      we survey the process of testing BE and advocate the likelihood paradigm for
      representing the resulting data as evidence. We emphasize the unique conflicts
      between hypothesis testing and confidence intervals in this area--which we
      believe are indicative of the existence of the systemic defects in the
      frequentist approach--that the likelihood paradigm avoids. We suggest the direct
      use of profile likelihoods for evaluating BE. We discuss how the likelihood
      approach is useful to present the evidence for both average and population BE
      within a unified framework. We also examine the main properties of profile
      likelihoods and estimated likelihoods under simulation. This simulation study
      shows that profile likelihoods offer a viable alternative to the (unknown) true
      likelihood for a range of parameters commensurate with BE research.

PMID- 18618424
TI  - Synthesis of 2-oxoamides based on sulfonamide analogs of gamma-amino acids and
      their activity on phospholipase A2.
AB  - A variety of lipophilic 2-oxoamides containing sulfonamide analogs of gamma-amino
      acids as well as acyl sulfonamides of gamma-aminobutyric acid were synthesized.
      Their ability to inhibit intracellular GIVA cPLA2 and GVIA iPLA2 as well as
      secreted GV sPLA2 was evaluated. The sulfonamide group seems a bioisosteric group
      suitable to replace the carboxyl group in 2-oxoamide inhibitors of GVIA cPLA2.

PMID- 18618425
TI  - Variance identification and efficiency analysis in randomized experiments under
      the matched-pair design.
AB  - In his 1923 landmark article, Neyman introduced randomization-based inference to
      estimate average treatment effects from experiments under the completely
      randomized design. Under this framework, Neyman considered the statistical
      estimation of the sample average treatment effect and derived the variance of the
      standard estimator using the treatment assignment mechanism as the sole basis of
      inference. In this paper, I extend Neyman's analysis to randomized experiments
      under the matched-pair design where experimental units are paired based on their
      pre-treatment characteristics and the randomization of treatment is subsequently
      conducted within each matched pair. I study the variance identification for the
      standard estimator of average treatment effects and analyze the relative
      efficiency of the matched-pair design over the completely randomized design. I
      also show how to empirically evaluate the relative efficiency of the two designs
      using experimental data obtained under the matched-pair design. My randomization
      based analysis differs from previous studies in that it avoids modeling and other
      assumptions as much as possible. Finally, the analytical results are illustrated
      with numerical and empirical examples.

PMID- 18618426
TI  - Flexible regression models for estimating postmortem interval (PMI) in forensic
      medicine.
AB  - Correct determination of time of death is an important goal in forensic medicine.
      Numerous methods have been described for estimating postmortem interval (PMI),
      but most are imprecise, poorly reproducible and/or have not been validated with
      real data. In recent years, however, some progress in PMI estimation has been
      made, notably through the use of new biochemical methods for quantifying relevant
      indicator compounds in the vitreous humour. The best, but unverified, results
      have been obtained with [K+] and hypoxanthine [Hx], using simple linear
      regression (LR) models. The main aim of this paper is to offer more flexible
      alternatives to LR, such as generalized additive models (GAMs) and support vector
      machines (SVMs) in order to obtain improved PMI estimates. The present study,
      based on detailed analysis of [K+] and [Hx] in more than 200 vitreous humour
      samples from subjects with known PMI, compared classical LR methodology with GAM
      and SVM methodologies. Both proved better than LR for estimation of PMI. SVM
      showed somewhat greater precision than GAM, but GAM offers a readily
      interpretable graphical output, facilitating understanding of findings by legal
      professionals; there are thus arguments for using both types of models. R code
      for these methods is available from the authors, permitting accurate prediction
      of PMI from vitreous humour [K+], [Hx] and [U], with confidence intervals and
      graphical output provided.

PMID- 18618427
TI  - Bayesian transformation cure frailty models with multivariate failure time data.
AB  - We propose a class of transformation cure frailty models to accommodate a
      survival fraction in multivariate failure time data. Established through a
      general power transformation, this family of cure frailty models includes the
      proportional hazards and the proportional odds modeling structures as two special
      cases. Within the Bayesian paradigm, we obtain the joint posterior distribution
      and the corresponding full conditional distributions of the model parameters for
      the implementation of Gibbs sampling. Model selection is based on the conditional
      predictive ordinate statistic and deviance information criterion. As an
      illustration, we apply the proposed method to a real data set from dentistry.

PMID- 18618428
TI  - Fitting stratified proportional odds models by amalgamating conditional
      likelihoods.
AB  - Classical methods for fitting a varying intercept logistic regression model to
      stratified data are based on the conditional likelihood principle to eliminate
      the stratum-specific nuisance parameters. When the outcome variable has multiple
      ordered categories, a natural choice for the outcome model is a stratified
      proportional odds or cumulative logit model. However, classical conditioning
      techniques do not apply to the general K-category cumulative logit model (K>2)
      with varying stratum-specific intercepts as there is no reduction due to
      sufficiency; the nuisance parameters remain in the conditional likelihood. We
      propose a methodology to fit stratified proportional odds model by amalgamating
      conditional likelihoods obtained from all possible binary collapsings of the
      ordinal scale. The method allows for categorical and continuous covariates in a
      general regression framework. We provide a robust sandwich estimate of the
      variance of the proposed estimator. For binary exposures, we show equivalence of
      our approach to the estimators already proposed in the literature. The proposed
      recipe can be implemented very easily in standard software. We illustrate the
      methods via three real data examples related to biomedical research. Simulation
      results comparing the proposed method with a random effects model on the
      stratification parameters are also furnished.

PMID- 18618429
TI  - Quantifying the usefulness of PD biomarkers in Phase 2 screening trials of
      oncology drugs.
AB  - This paper develops a framework for evaluating the usefulness of a PD biomarker
      as a primary endpoint in a Phase 2 screening trial of an oncology drug. We judge
      the contribution of the PD biomarker by assessing its impact on the efficiency of
      the drug development process. 'Efficiency' is defined as the probability that an
      active drug is found to be effective in Phase 3 divided by the sum of the
      expected number of events in Phase 3 and the pre-Phase 2 drug development costs
      appropriately normalized. We show that 20 Phase 2 trials of different
      experimental treatments can provide a reasonable answer as to whether a PD
      biomarker makes a positive or negative contribution to the drug development
      process.

PMID- 18618430
TI  - Binding of synthetic fragments of beta-endorphin to nonopioid beta-endorphin
      receptor.
AB  - Selective agonist of nonopioid beta-endorphin receptor decapeptide immunorphin
      (SLTCLVKGFY) was labeled with tritium (the specific activity of 24 Ci/mmol).
      [3H]Immunorphin was found to bind to nonopioid beta-endorphin receptor of mouse
      peritoneal macrophages (Kd = 2.0 +/- 0.1 nM). The [3H]immunorphin specific
      binding with macrophages was inhibited by unlabeled beta-endorphin (Ki = 2.9 +/-
      0.2 nM) and was not inhibited by unlabeled naloxone, alpha-endorphin, gamma
      endorphin and [Met5]enkephalin (Ki > 10 microM). Thirty fragments of beta
      endorphin have been synthesized and their ability to inhibit the [3H]immunorphin
      specific binding to macrophages was studied. Unlabeled fragment 12-19 (TPLVTLFK,
      the author's name of the peptide octarphin) was found to be the shortest peptide
      possessing practically the same inhibitory activity as beta-endorphin (Ki = 3.1
      +/- 0.3 nM). The peptide octarphin was labeled with tritium (the specific
      activity of 28 Ci/mmol). [3H]Octarphin was found to bind to macrophages with high
      affinity (Kd = 2.3 +/- 0.2 nM). The specific binding of [3H]octarphin was
      inhibited by unlabeled immunorphin and beta-endorphin (Ki = 2.4 +/- 0.2 and 2.7
      +/- 0.2 nM, respectively).

PMID- 18618431
TI  - Comparisons between ITT and treatment emergent adverse event analyses.
AB  - Different from the use of intention-to-treat (ITT) analysis for efficacy
      evaluation, many pharmaceutical companies currently use treatment emergent (TE)
      analysis for adverse event (AE) safety analysis. In the TE analysis, study period
      and AEs occurring after a pre-specified post-treatment window will not be
      included. One consideration for using the TE AE analysis is that including
      substantial off-drug period and events in the analysis may dilute the power for
      detecting safety signals especially if after discontinuation residual treatment
      effect diminishes quickly. We perform quantitative analyses to compare the
      unbiasedness and power of the ITT and TE AE analyses under several different
      settings and metrics (difference in rates and relative risk). Results show that
      unbiasedness and power are not always in the same direction. The choice of an
      approach for a particular trial should depend on the focus of the analysis. A
      data example is used to illustrate these points.

PMID- 18618432
TI  - Survey of prophylactic antibiotic use amongst UK cochlear implant surgeons.
AB  - Cochlear implant patients are at an increased risk of pneumococcal meningitis.
      Recent government guidelines require all implant patients to undergo pneumococcal
      vaccination. The guidelines also suggest antibiotic prophylaxis but no clear
      guidelines regarding which antibiotic to use or for how long were issued.We asked
      each implant centre within the UK to describe their antibiotic protocol for
      cochlear implantation.Our results have showed that 100% of UK implant surgeons
      use antibiotic prophylaxis. The type of antibiotic and duration vary
      significantly between centres. Interestingly, however, the regimes followed by
      most practices do not adhere to surgical principles of antibiotic prophylaxis.

PMID- 18618435
TI  - Influence of the extraction mode on the yield of hyperoside, vitexin and vitexin
      2''-O-rhamnoside from Crataegus monogyna Jacq. (hawthorn).
AB  - INTRODUCTION: The extract of Crataegus monogyna shows sedative, hypotensive,
      vasodilator and cardio-tonic actions. Although several papers dealing with the
      extraction of metabolites from Crataegus have been published, the plant
      productivity in terms of bioactive compounds is not easily understandable as yet.
      OBJECTIVE: To investigate the influence of the extraction mode on the yield of
      bioactive compounds from Crataegus monogyna Jacq. in order to evaluate plant
      productivity. METHODOLOGY: Samples were prepared by extraction of powdered
      material obtained from top branches, flowers and leaves. Soxhlet extraction,
      maceration and ultrasound- and microwave-assisted extraction at different
      experimental conditions were investigated for the exhaustive extraction of
      hyperoside, vitexin and vitexin-2''-O-rhamnoside. The phytocomponents were
      identified and quantified by HPLC-UV/PAD, comparing HPLC retention times and UV
      spectra of individual peaks with those of the standards analysed under the same
      conditions. RESULTS: An easy-to-use HPLC isocratic method suitable for the
      quantification of hyperoside, vitexin and vitexin-2''-O-rhamnoside in raw plant
      extracts was developed. The optimised HPLC methodology was applied to evaluate
      different extraction procedures. The ultrasound and microwave-assisted extraction
      protocols showed higher extraction efficiency than the others. In particular, the
      optimised microwave protocol gave rise to the highest extraction efficiency with
      high reproducibility. CONCLUSIONS: A microwave protocol combined with isocratic
      HPLC analysis is proposed for the rapid screening of plant materials collected in
      different environmental conditions in order to evaluate the productivity of
      Crataegus monogyna Jacq. and to find out the best ecological conditions to
      cultivate hawthorn in Northern Italy.

PMID- 18618436
TI  - Safety assessment of food and herbal products containing hepatotoxic
      pyrrolizidine alkaloids: interlaboratory consistency and the importance of N
      oxide determination.
AB  - INTRODUCTION: Two recent mass spectrometry-based reports concerning Senecio
      scandens yielded remarkably dissimilar pyrrolizidine alkaloid constituents. In
      both studies, and in a related analysis of Senecio scandens and Tussilago farfara
      using micellar electrokinetic chromatography, the presence of hazardous N-oxides
      of the alkaloids was either not considered or was inadequately considered. This
      raises concerns about the effectiveness of the methodologies used in these, and
      similar, studies in assessing the pyrrolizidine alkaloid content and the safety
      of food, food supplements and medicines for human use. OBJECTIVE: To highlight
      essential analytical requirements for confident assessment of pyrrolizidine
      alkaloid-related safety of food and herbal products for human use. METHODOLOGY:
      Direct infusion-ESI MS and HPLC-ESI MS were used to analyse samples derived from
      liquid-liquid partitioning experiments and from strong cation exchange, solid
      phase extraction of pyrrolizidine alkaloids and their N-oxides. RESULTS: A simple
      solvent partitioning experiment using pure senecionine and senecionine-N-oxide,
      two constituents reported in one of the mass spectrometry-based studies of S.
      scandens, clearly demonstrated the inadequacy of the reported method to detect
      and quantitate hazardous pyrrolizidine alkaloid N-oxide components. A preliminary
      LCMS analysis of commercially-prepared extracts of comfrey roots (Symphytum
      officinale and S. uplandicum s. l.) was used as a model to highlight the
      analytical importance of N-oxides in the safety assessment of pyrrolizidine
      alkaloid-containing medicinal herbs. CONCLUSIONS: This study highlighted
      significant differences in the reported identification of pyrrolizidine alkaloids
      from the same plant species, and clearly demonstrated the inadequacy of some
      procedures to include N-oxides in the assessment of pyrrolizidine alkaloid
      related safety of food and herbal products.

PMID- 18618439
TI  - Development and application of thermo-sensitive immunomicrospheres for antibody
      purification.
AB  - The latex particles composed of poly(styrene/N-isopropylacrylamide/glycidyl
      methacrylate) [P(St/NIPAM/GMA)] and poly(styrene/N
      isopropylacrylamide/methacrylic acid) [P(St/NIPAM/MAA)] were prepared by
      emulsifier-free emulsion polymerization. These latex particles with submicrometer
      size showed the thermosensitivity originated from the thermo-sensitive nature of
      NIPAM. That is, the minimum NaCI concentration for flocculation of these latex
      particles [critical flocculation concentration (CFC)] decreased significantly
      with increasing temperature and reached constant values at above the critical
      temperature [critical flocculation temperature (CFT)]. At a certain NaCl
      concentration, the thermo-sensitive latex particles were flocculated by raising
      temperature, and conversely, the flocculated thermo-sensitive latex particles
      were completely dispersed by lowering temperature. Bovine serum albumin (BSA) was
      covalently immobilized onto the P(St/NIPAM/GMA) and P(St/NIPAM/MMA) latex
      particles with high efficiency. The BSA-immobilized P(St/NIPAM/GMA) and
      P(St/NIPAM/MAA) latex particles (immunomicrospheres) showed the similar
      dependencies of CFC on temperature to the bare latex particles. These thermo
      sensitive immunomicrospheres were successfully used for the immunoaffinity
      purification of anti-BSA antibodies from antiserum.

PMID- 18618440
TI  - Anaerobic acidogenesis of primary sludge: the role of solids retention time.
AB  - This research investigates the effect of solids retention time (SRT) on the acid
      phase anaerobic digestion of primary sludge. A series of experiments were
      conducted using two continuous-flow 3-L units with the following configuration: a
      completely mixed reactor (CMR) with clarifier and solids recycle and an upflow
      anaerobic sludge blanket (UASB) reactor. Results show that C(2) to C(5) volatile
      fatty acids (VFA) were the predominant compounds formed. At a constant hydraulic
      retention time (HRT) of 12 h, variation in SRT from 10 to 20 days resulted in a
      slight increase in VFA production in both systems, but at a shorter SRT (5 days)
      a drastic drop in acid production was observed. In addition, the percent
      distribution of VFA was to some extent affected by the change in SRT. On the
      other hand, organic matter degradation [measured by the chemical oxygen demand
      (COD) specific solubilization rate or the percent volatile suspended solids (VSS)
      reduction] appeared to be independent of SRT, at least in the range investigated.
      The percent soluble COD in the form of VFA, however, increased steadily with
      increasing SRT, approaching the 90% level at 20 days. The remaining soluble COD
      in the effluent from these systems may be mainly attributed to metabolic
      intermediates and unused soluble substrate.

PMID- 18618437
TI  - A Rapid and effective method for RNA extraction from different tissues of
      grapevine and other woody plants.
AB  - INTRODUCTION: RNA quality and integrity are critical for many studies in plant
      molecular biology. High-quality RNA extraction from grapevine and other woody
      plants is problematic due to the presence of polysaccharides, polyphenolics and
      other compounds that bind or co-precipitate with the RNA. OBJECTIVE: To develop
      an optimised cetyltrimethylammonium bromide (CTAB)-based protocol, to reduce the
      time and cost of extraction without reducing quality and yield of RNA extracted
      from polysaccharide-rich tissues of several plants. METHODOLOGY: Several changes
      were introduced to the original CTAB protocol. All centrifugation steps were
      carried out at 4 degrees C, the sample weight was decreased and the
      concentrations of PVP-40 and LiCl were increased reducing incubation time prior
      to RNA precipitation. This rapid CTAB protocol was compared with six different
      RNA extraction methods from three grapevine tissues, namely, in vitro plantlets,
      and leaves and mature canes from actively growing field vines. RESULTS: The rapid
      CTAB method gave high-quality RNA in only 3 h at low cost with efficiency equal
      to or higher than that obtained with other time-consuming and expensive
      protocols. The procedure was applied to RNA extraction from other grapevine
      tissues and other woody species including olive, lemon, poplar, chestnut, apple,
      pear, peach, cherry, apricot, plum and kiwi fruit. RNA of high quality could be
      isolated from all tissues and from all species. CONCLUSION: The study has shown
      that the improvement of a CTAB-based protocol allows the rapid isolation of high
      quality RNA from grapevine and many woody species.

PMID- 18618441
TI  - Two-phase airlift fermentor operation with elicitation for the enhanced
      production of enzophenanthridine alkaloids in cell suspensions of Escherichia
      californica.
AB  - Approaches to increasing the productivity of benzophenanthridine alkaloids in
      suspension cultures in Escherichia californica were made in an airlift fermentor
      under different culture conditions. Elicitation with yeast extract elicitor
      reduced the time required to obtain a certain amount of alkaloid production. In a
      two-phase airlift fermentor with compounded silicone fluid, total alkaloid
      concentration in silicone fluid was 153.1 mg/L and that in the aqueous cellular
      phase was 8.2 mg/L at day 21 from inoculation. The large accumulation capacity of
      silicone fluid made it possible to store correspondingly large amounts of total
      alkaloid and increased the alkaloid production. Act day 21 from inoculation, the
      volumetric alkaloid productivity and the netproduction in a two-phase airlift
      fermentor were 1.4 and 1.5 times higher than those of normal airlift fermentor
      operation. This performance was furthermore enhanced by elicitation. Elicitation
      in two-phase airlift fermentor operation increased the volumetric productivity
      and the new production 3.3- and 3.5-fold compared to those of normal airlift
      fermentor operation.

PMID- 18618442
TI  - Cultivation of an L-lactate dehydrogenase mutant of Bacillus stearothermophilus
      in continuous culture with cell recycle.
AB  - Continuous fermentation with cell recycle proved very effective in increasing the
      ethanol volumetric productivity of the thermophilic facultative anaerobe,
      Bacillus stearothermophilus strain LLD-15, on sucrose at 70 degrees C. When
      complete cell recycle was used, cell viability decreased after a few residence
      times and sucrose consumption was reduced. Operation using a constant bleed rate
      resulted in greater stability and higher ethanol volumetric productivities. A
      mathematical model based on maintenance energy requirements provided an adequate
      description of the system.

PMID- 18618443
TI  - Physicochemical properties of the matrix proteins of three main culture vehicles.
AB  - The protein components of three industrial recombinant expression systems:
      Escherichia coli, Saccharomyces cerevisiae, and a mammalian cell culture
      supernatant of CHO cells were characterized in terms of their molecular weight,
      isoelectric point, and relative surface hydrophobicity. Identification of
      individual proteins was done by reference to their position in protein band
      profiles by polyacrylamide gel electrophoresis (PAGE) of the crude material. This
      permitted a rapid and facile assignment of quantitative values for these three
      parameters to all the major protein components in these materials. Because it is
      the indigenous proteins in expression systems that will form the bulk of any
      impurities in the product, once the values of these parameters are known for any
      target recombinant protein, the data obtained will enable appropriate expression
      systems to be chosen for minimizing amounts of potential contaminants and
      reducing downstream processing requirements and costs. The data will also
      indicate which fractionation steps (i.e., charge, size or hydrophobicity-based)
      are likely to be best for distinguishing between target and contaminant proteins,
      thus aiding and early removal of the maximum quantities of undesired protein to
      bring subsequent bioseparation steps down in scale and cost and up in terms of
      efficiency.

PMID- 18618444
TI  - A novel method to prepare size-regulated spheroids composed of human dermal
      fibroblasts.
AB  - A simple method to prepare size-regulated spheroids has been successfully
      developed by combining a temperature responsive polymer, poly-N-isopropyl
      acrylamide (PNIPAAm), conjugated with collagen and ultraviolet (UV) irradiation
      with photomasks. The coating layer composed of PNIPAAm conjugated with collagen
      functions as a cell substratum at 37 degrees C, then when lowering the
      temperature of culture medium the cells attached to it detach as a self
      supporting sheet. This is because PNIPAAm dissolves into the culture medium below
      the lower critical solution temperature LCST; about 30 degrees C, but it is
      insoluble above the LCST. The detached cell sheet forms a multicellular spheroid.
      On the other hand, UV effectively immobilized collagen in the coating layer
      because UV generates crosslinkages in collagen molecules. Crosslinkages were
      quantitatively introduced by controlling the energy of UV-irradiation thus the
      ability of human dermal fibroblasts to attach to and detach from the surface was
      tightly controlled. When the collagen content in the coating layer was 9
      microg/cm(2) (collagen ratio, 4.5%), UV-irradiation energy of 2000 J/m(2) was
      suitable to obtain 100% of the attachability and detachability. However, the
      cells did not attach to the nonirradiated surface at this collagen content
      because insufficient collagen was immobilized. Using photomakes to apply UV
      irradiation, it was possible to obtain cell-adhesive areas(irradiated areas) and
      nonadhesive areas (nonirradiated areas) on the same surface. Consequently,
      spheroids of any size and in any number from one dish were prepared. The
      viability of cells in spheroids 350 microm in diameter was maintained at a high
      level for 28 days; however, viability of spheroids 800 microm in diameter rapidly
      decreased for 2 days. The size was very important to maintain the viability. This
      novel method is useful to develop size-regulated spheroids for different
      applications; for example, in toxicology tests.

PMID- 18618445
TI  - Glycolipid membrane anchored recombinant protein production from CHO cells
      cultGred on porous microcarriers.
AB  - Recombinant proteins were harvested from Chinese hamster ovary (CHO) cells by a
      controlled release process, which increased the purity and concentration of the
      harvested protein. Recombinant human melano-transferrin (p97) was expressed
      linked to the outer surface of CHO cells by a glycosyl-phosphatidylinositol (GPI)
      membrane anchor. Cells were grown to confluence in T-flask culture, and the p97
      harvested by replacing the growth medium for 30 min with phosphate-buffered
      saline (PBS) containing 10 mU/mL phosphatidylinositol-phospholipase C (PI-PLC).
      The GPI anchor was selectively cleaved by PI-PLC. In fresh medium, the CHO cells
      regained over 95% of their p97 expression within 40 h. The process was repeated
      for eight harvests. Harvested protein concentrations varied from 1.5 to 3.8
      microg/mL due to difficulties in maintaining stable confluent T-flask cultures.
      Harvesting from cells growing on porous microcarriers was investigated to
      increase p97 product concentrations and to overcome culture stability problems.
      Semicontinuous cultures were maintained in spinners for up to 76 days with
      average bioreactor cell densities of over 10(7) cell/mL. The p97 was harvested at
      up to 100 microg/mL and 30% purity with protein production remaining stable for 4
      harvest cycles. Production of high levels of p97 from CHO cells was maintained at
      0.5% serum.

PMID- 18618446
TI  - Affinity cross-flow filtration: purification of IgG with a novel protein a
      affinity matrix prepared from two-dimensional protein crystals.
AB  - In this article, we describe the use of 1- to 2-mum sized affinity microparticles
      for the isolation and purification of IgG from artificial IgG-human serum albumin
      mixtures and clarified hybridoma cell culture supernatants by affinity cross-flow
      filtration. Affinity microparticles were prepared from cell wall fragments of
      Clostridium thermohydrosulfuricum L111-69, in which the peptidoglycan-containing
      layer was completely covered with a hexagonally ordered S-layer lattice. After
      crosslinking the S-layer protein with glutaraldehyde, carboxyl groups from acidic
      amino acids were activated with carbodiimide and used for immobilization of
      Protein. A. Quantitative determination confirmed that Protein A molecules formed
      a monomolecular layer on the outermost surface of the S-layer lattice. Affinity
      microparticles were found to withstand high centrifugal and shear forces and
      revealed no Protein A leakage or S-layer protein release under cross-flow
      conditions between pH 2 to 12. The IgG-binding capacity of affinity
      microparticles was investigated under crossflow conditions and compared with that
      obtained in batch adsorption processes.

PMID- 18618447
TI  - Redox conditions for stimulation of in vitro folding and assembly of the
      glycoprotein hormone chorionic gonadotropin.
AB  - The formation of native disulfide bonds during in vitro protein folding can be
      limiting in obtaining biologically active proteins. Thus, optimization of redox
      conditions can be critical in maximizing the yield of renatured, recombinant
      proteins. We have employed a folding model, that of the beta subunit of human
      chorionic gonadotropin (hCG- beta), to investigate in vitro oxidation conditions
      that facilitate the folding of this protein, and have compared the in vitro rates
      obtained with the rate of folding that has been observed in intact cells. Two
      steps in the folding pathway of hCG-beta were investigated: the rate-limiting
      events in the folding of this protein, and the assembly of hCG-beta with, hCG
      alpha. The rates of these folding events were determined with and without protein
      disulfide isomerase (PDI) using two different types of redox reagents: cysteamine
      and its oxidized equivalent, cystamine, and reduced and oxidized glutathione.
      Rates of the rate-limiting folding events were twofold faster in
      cysteamine/cystamine redox buffers than in glutathione buffers in the absence of
      PDI. Optimal conditions for hCG-beta folding were attained in a 2 mM glutathione
      buffer, pH 7.4, that contained 1 mg/mL PDI and in 10 microM cysteamine/cystamine,
      pH 8.7, without PDI. Under these conditions, the half-time of the ratelimiting
      folding event was 16 to 20 min and approached the rate observed in intact cells
      (4 to 5 min). Moreover, folding of the beta subunit under these conditions yields
      a functional protein, based on its ability to assemble with the alpha subunit.
      The rates of assembly of hCG-beta with hCG-alpha in the cysteamine/cystamine or
      glutathione/PDI redox buffers were comparable (t(1/2/sb> = 9 to 12 min)). These
      studies show that rates of folding and assembly events that involve disulfide
      bond formation can be optimized by a simple buffer system composed of cysteamine
      and cystamine.

PMID- 18618448
TI  - A differential scanning calorimetric study of chymotrypsin in the presence of
      added polymers.
AB  - Scanning calorimetry measurements of different amounts of chymotrypsin in water
      alone gave a temperature of denaturation (T(d)) value of 54 degrees C. However,
      when high-molecular-weight poly(ethylene glycol) was added to aqueous solutions
      of chymotrypsin, the thermostability of the enzyme was enhanced. For example, the
      addition of 20% (w/w) of poly(ethylene glycol) of molecular weight of 100,000
      increased the T(d/) value to 66 degrees C. In toluene containing various amounts
      of added water, ethyl cellulose was used to improve the thermostability of
      chymotrypsin. For this system, a T(d) value of 82 degrees C was obtained with a
      20% (w/w/) concentration of ethyl cellulose and 2% (v/v) of added water. Polymers
      in these solvents interact with water, which could otherwise denature the enzyme;
      polymers also from complexes with enzyme molecules to produce a more stable
      structure.

PMID- 18618449
TI  - Production of lignin peroxidase by Phanerochaete chrysosporium immobilized on
      porous poly(styrene-divinylbenzene) carrier and its application to the degrading
      of 2-chlorophenol.
AB  - Porous poly(styrene-divinylbenzene) carriers, for the immobilization of white rot
      fungus Phanerochaete chrysosporium have been prepared by the concentrated
      emulsion polymerization method. The concentrated emulsion consists of a mixture
      of styrene and divinylbenzene containing a suitable surfactant and an initiator
      as the continuous phase, and water as the dispersed phase. The polymerization of
      the monomers of the continuous phase generated the polymer carrier with a porcus
      structure. The white rot fungus Phanerochaete chrysosporium has been immobilized
      on porous poly(styrene-divinylbenzene) carriers and used for the batch production
      and the repeated batch production of lignin peroxidase in shake cultures based on
      a carbon-limited medium containing veratryl alcohol. The best results were
      achieved when a spore inoculum was used for immobilization instead of 1-day-old
      mycelial pellets, for both the batch production and the repeated batch
      production. The porous poly(styrene-divinylbenzene) immobilized Phanerochaete
      chrysosporium and freely suspended mycelial pellets were used as biocatalysts for
      the degradation of 2-chilorophenol in a 2-L bioreactor. The porous poly(styrene
      divinylbenzene) particle (diameter congruent with 0.2 cm) immobilized spores
      exhibited a much higher activity in the degradation of 2-chlorophenol than the
      freely suspended mycelial pellets.

PMID- 18618450
TI  - Fuzzy supervisory control of glutamic acid production.
AB  - In glutamic acid fermentation, the molasses feeding policy and time of penicillin
      addition significantly affected glutamic acid production, and a fuzzy supervisory
      control system was developed for their quasi-optimal regulation.From the trend of
      the experimental data, production rules and membership functions of fuzzy
      inference were devised to determine the quasi-optimum molasses feeding policy and
      penicillin addition time. A computer with multitasking operating system was used
      for the construction of the control system with fuzzy inferencing, which decided
      the control policy every minute, and the feed rate was controlled automatically.
      The pattern of residual sugar concentration was almost the same as that of
      maximum glutamic acid production under manual operation. Using the computer
      control system, stable production was maintained at the highest level of 71 to 75
      g/L.

PMID- 18618451
TI  - Growth characteristics in fed-batch culture of hybridoma cells with control of
      glucose and glutamine concentrations.
AB  - An online system using HPLC was developed for the measurement of glucose,
      glutamine, and lactate in a culture broth. Using the system, the glucose and
      glutamine concentrations were controlled simultaneously by an adaptive-control
      algorithm within the ranges of 0.2 to 2.0 and 0.1 to 0.6 g/L, respectively. When
      the glucose concentration was controlled at the low level of 0.2 g/L, the
      intracellular lactate dehydrogenase activity decreased by one-half and the
      lactate concentration by one-third, whereas the uptake rates of serine and
      glycine were about twice as high, compared with the amounts when the glucose
      concentration was controlled at 1.0 g/L. On the other hand, ammonia production
      increased when the glucose concentration was kept low. To reduce the production
      of inhibitory metabolites such as ammonia and lactate and improve the antibody
      production rate in a hybridoma cell culture, the concentrations of glucose and
      glutamine were controlled at 0.2 and 0.1 g/L, respectively. With these low
      concentrations of glucose and glutamine, the cell concentration (4.1 x 10(6)
      cells/mL) and antibody production (172 mg/L) both increased about twofold
      compared with the amounts when the glucose was controlled at higher levels. From
      these results, simultaneous control of the glucose and glutamine concentrations
      was shown to be useful in the production of antibody by hybridoma cell
      cultivation.

PMID- 18618452
TI  - Modeling approach to control of carbohydrate metabolism during citric acid
      accumulation by Aspergillus niger: I. Model definition and stability of the
      steady state.
AB  - A model of the carbohydrate metabolism and the anaplerotic synthesis of
      oxalacetate in Aspergillus niger, under conditions of citric and accumulation, is
      presented. In this first article we set the stage for subsequent analysis within
      the framework of the biochemical system theory (BST): we formulate the model and
      develop the system representation in power law forms, showing that the steady
      state is locally stable. In the second article, the control structure of the
      system is described and a rationale for the optimization of the process is
      developed.

PMID- 18618453
TI  - Modeling approach to control of carbohydrate metabolism during citric acid
      accumulation by Aspergillus niger: II. Sensitivity analysis.
AB  - Steady state sensitivity analysis of a model of carbohydrate metabolism and
      anaplerotic synthesis of oxalacetate were, in Aspergillus niger under conditions
      of citric acid accumulation, carried out. The flux and metabolite concentration
      control structure of the system obtained shows that the hexokinase/substrate
      transport step is the main controlling step of the pathway. The quantitative
      contribution of the other enzyme catalyzed or transport steps are also discussed.
      These results allow the design of a proper strategy of biotechnological
      manipulation aimed at improvement of the process.

PMID- 18618454
TI  - Lipase catalyzed esterification of glycidol in nonaqueous solvents: solvent
      effects on enzymatic activity.
AB  - We studied the effect of organic solvents on the kinetics of porcine pancreatic
      lipase (pp) for the resolution of racemic glycidol through esterification with
      butyric acid. We quantified ppl hydration by measuring water sorption isotherms
      for the enzyme in the solvents/mixtures tested. The determination of initial
      rates as a function of enzyme hydration revealed that the enzyme exhibits maximum
      apparent activity in the solvents/mixtures at the same water content (9% to 11%
      w/w) within the associated experimental error. The maximum initial rates are
      different in all the media and correlate well with the logarithm of the molar
      solubility of water in the media, higher initial rates being observed in the
      solvents/mixtures with lower water solubilities. The data for the mixtures
      indicate that ppl apparent activity responds to bulk property of the solvent.
      Measurements of enzyme particle sizes in five of the solvents, as function of
      enzyme hydration, revealed that mean particle sizes increased with enzyme
      hydration in all the solvents, differences between solvents being more pronounced
      at enzyme hydration levels close to 10%. At this hydration level, solvents having
      a higher water content lead to lower reaction rates; these are the solvents where
      the mean enzyme particle sizes are greater. Calculation of the observable modulus
      indicates there are no internal diffusion limitations. The observed correlation
      between changes in initial rates and changes in external surface area of the
      enzyme particles suggests that interfacial activation of ppl is only effective at
      the external surface of the particles. Data obtained for the mixtures indicate
      that ppl enantioselectivity depends on specific solvent-enzyme interactions. We
      make reference to ppl hydration and activity in supercritical carbon dioxide.

PMID- 18618455
TI  - Desulfurization of coal by microbial column flotation.
AB  - Twenty-three strains capable of oxidizing iron were isolated from coal and ore
      storage sites as well as coal and ore mines, volcanic areas, and hot spring. Four
      strains were found to have high iron-oxidizing activity. One strain (T-4) was
      selected for this experiment since the strain showed the fastest leaching rate of
      iron and sulfate from pyrite among the four strains. The T-4 strain was assigned
      for Thiobacillus ferrooxidans from its cultural and morphological
      characteristics.Bacterial treatment was applied to column flotation. An increase
      of cell density in the microbial column flotation resulted in the increase of
      pyrite removal from a coal-pyrite mixture (high sulfur imitated coal) with
      corresponding decrease of coal recovery. The addition of kerosene into the
      microbial column flotation increased the recovery of the imitated coal from 55%
      (without kerosene) to 81% (with 50 microL/L kerosene) with the reduction of
      pyrite sulfur content from 11% (feed coal) to 3.9% (product coal). The kerosene
      addition could reduce the pyritic sulfur content by collecting the coal in the
      recovery. However, the addition could not enhance separation of pyrite from the
      coal-pyrite mixture, since pyrite rejection was not affected by the increase of
      the kerosene addition. An excellent separation was obtained by the microbial
      flotation using a long column which had a length-diameter (L/D) ratio of 12.7.
      The long column flotation reduced the pyritic sulfur content from 11% (feed coal)
      to 1.8% (product coal) when 80% of the feed coal was recovered without the
      kerosene addition. The long column flotation not only attained an excellent
      separation but also reduced the amount of cells for desulfurization to as little
      as one-tenth of the reported amount.

PMID- 18618456
TI  - Overproduction of glycogen in Escherichia coli blocked in the acetate pathway
      improves cell growth.
AB  - Excessive production of acetate is a problem frequently encountered in aerobic
      high-cell-density fermentations of Escherichia coli. Here, we have examined
      genetic alterations resulting in glycogen overproduction as a possible means to
      direct the flux of carbon away from the acetate pool. Glycogen overaccumulation
      was achieved either by using a regulatory glgQ mutation or by transforming cells
      with a plasmid containing the glycogen biosynthesis genes glgC (encoding ADPG
      pyrophosphorylase) and glgA (encoding glycogen synthase) under their native
      promoter. Both strategies resulted in an approximately five-fold increase in
      glycogen levels but had no significant effect on acetate excretion. The glgC and
      glgA genes were then placed under the control of the isopropyl---D
      thiogalactopyranoside (IPTG) inducible tac promoter, and this construct was used
      to stimulate glycogen production in a mutant defective in acetate biosynthesis
      due to deletion of the ack (acetate kinase) and pta (phosphotransacetylase)
      genes. If glycogen overproduction in the ack pta strain was induced during the
      late log phase, biomass production increased by 15 to 20% relative to uninduced
      controls. Glycogen overaccumulation had a significant influence on carbon
      partitioning: The output of carbon dioxide peaked earlier than in the control
      strain, and the levels of an unusual fermentation byproduct, pyruvate, were
      reduced. Exogenous pyruvate was metabolized more rapidly, suggesting higher
      activity of gluconeogenesis or the tricarboxylic acid (TCA) cycle as a result of
      glycogen overproduction. Potential mechanisms of the observed metabolic
      alterations are discussed. Our results suggest that ack pta mutants over
      producing glycogen may be a suitable starting point for constructing E. coli
      strains with improved characteristics in high-cell-density fermentations.

PMID- 18618457
TI  - On protein solubility in organic solvent.
AB  - Solubility of a model protein, hen egg-white lysozyme, was investigated in a wide
      range of neat nonaqueous solvents and binary mixtures thereof. All solvents that
      are protic, very hydrophilic, and polar readily dissolve more than 10 mg/mL of
      lysozyme (lyophilized from aqueous solution of pH 6.0). Only a marginal
      correlation was found between the lysozyme solubility in a non-aqueous solvent
      and the letter's dielectric constant or Hildebrand solubility parameter, and no
      correlation was observed with the dipole moment. Lysozyme dissolved in dimethyl
      sulfoxide (DMSO) could be precipitated by adding protein nondissolving co
      solvents, although the enzyme had a tendency to form supersaturated solutions in
      such mixtures. The solubility of lysozyme, both in an individual solvent (1,5
      pentanediol) and in binary solvent mixtures (DMSO/acetonitrile), markedly
      increased when the pH of the enzyme aqueous solution prior to lyophilization was
      moved away from the proteins's isoelectric point.

PMID- 18618458
TI  - Collagen fabrics as biomaterials.

PMID- 18618459
TI  - Use of quasi-isoelectric buffers to limit protein adsorption in capillary zone
      electrophoresis.
AB  - The use of quasi-isoelectric buffers consisting of narrow pH cuts of carrier
      ampholytes (NC) has been investigated to limit protein adsorption on capillary
      walls during capillary zone electrophoresis experiments. To quantify protein
      adsorption on the silica surface, a method derived from that of Towns and Regnier
      has been developed. alpha-Lactalbumin (14 kDa, pI 4.8) and alpha-chymotrypsinogen
      A (25 kDa, pI 9.2) have been used as model proteins. Acidic narrow pH cuts of
      carrier ampholytes (NC, pH 3.0) obtained from fractionation of Serva 4-9 carrier
      ampholytes were used as BGE in bare-silica capillaries, and allowed to decrease
      significantly protein adsorption, as compared to experiments performed with
      classical formate buffer. The use of NC as BGE appeared to be as efficient as the
      use of polydimethylacrylamide coating to prevent protein adsorption. This
      increase of protein recovery when using NC was attributed to the interaction of
      carrier ampholytes with the silica surface, leading to a shielding of the
      capillary wall.

PMID- 18618460
TI  - A survey of foot problems in juvenile idiopathic arthritis.
AB  - BACKGROUND: Evidence suggests that foot problems are common in juvenile
      idiopathic arthritis (JIA), with prevalence estimates over 90%. The aim of this
      survey was to describe foot-related impairment and disability associated with JIA
      and foot-care provision in patients managed under modern treatment paradigms,
      including disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies.
      METHODS: The Juvenile Arthritis Foot Disability Index (JAFI), Child Health
      Assessment Questionnaire (CHAQ), and pain visual analogue scale (VAS) were
      recorded in 30 consecutive established JIA patients attending routine outpatient
      clinics. Foot deformity score, active/limited joint counts, walking speed, double
      support time (s) (DS) and step length symmetry index % (SI) were also measured.
      Foot-care provision in the preceding 12 months was determined from medical
      records. RESULTS: Sixty-three per cent of children reported some foot impairment,
      with a median (range) JAFI subscale score of 1 (0-3); 53% reported foot-related
      activity limitation, with a JAFI subscale score of 1 (0-4); and 60% reported
      participation restriction, with a JAFI subscale score of 1 (0-3). Other reported
      variables were CHAQ 0.38 (0-2), VAS pain 22 (0-79), foot deformity 6 (0-20),
      active joints 0 (0-7), limited joints 0 (0-31), walking speed 1.09 m/s (0.84-1.38
      m/s), DS 0.22 s (0.08-0.26 s) and SI +/-4.0% (+/-0.2-+/-31.0%). A total of 23/30
      medical records were reviewed and 15/23 children had received DMARDS, 8/23
      biologic agents and 20/23 multiple intra-articular corticosteroid injections. Ten
      children received specialist podiatry care comprising footwear advice, orthotic
      therapy and silicone digital splints together with intrinsic muscle strengthening
      exercises. CONCLUSION: Despite frequent use of DMARD/biologic therapy and
      specialist podiatry-led foot care, foot-related impairment and disability
      persists in some children with JIA.

PMID- 18618461
TI  - Underivatized cyclic olefin copolymer as substrate material and stationary phase
      for capillary and microchip electrochromatography.
AB  - We report, for the first time, the use of underivatized cyclic olefin copolymer
      (COC, more specifically: Topas) as the substrate material and the stationary
      phase for capillary and microchip electrochromatography (CEC), and demonstrate
      chromatographic separations without the need of coating procedures.
      Electroosmotic mobility measurements in a 25 microm id Topas capillary showed a
      significant cathodic EOF that is pH-dependent. The magnitude of the
      electroosmotic mobility is comparable to that found in glass substrates and other
      polymeric materials. Open-tubular CEC was employed to baseline-separate three
      neutral compounds in an underivatized Topas capillary with plate heights ranging
      from 5.3 to 12.7 microm. The analytes were detected using UV absorbance at 254
      nm, thus taking advantage of the optical transparency of Topas at short
      wavelengths. The fabrication of a Topas-based electrochromatography microchip by
      nanoimprint lithography is also presented. The microchip has an array of pillars
      in the separation column to increase the surface area. The smallest features that
      were successfully imprinted were around 2 microm wide and 5 microm high. No
      plasma treatment was used during the bonding, thus keeping the surface properties
      of the native material. An RP microchip electrochromatography separation of three
      fluorescently labeled amines is demonstrated on the underivatized microchip with
      plate heights ranging from 3.4 to 22 microm.

PMID- 18618462
TI  - The de Quervain's screening tool: validity and reliability of a measure to
      support clinical diagnosis and management.
AB  - BACKGROUND: Studies into the effectiveness of interventions for upper limb soft
      tissue disorders have been hampered by a lack of consistently used diagnostic
      criteria, meaning that comparison of research results is a problem. To aid
      homogeneous recruitment into a study of de Quervain's disease, a de Quervain's
      screening tool (DQST) was developed. This could also be used to facilitate
      clinical diagnosis and management in practice. AIMS: To provide evidence for the
      content and construct validity and test-retest and inter-rater reliability of the
      DQST. METHOD: The study was conducted in an acute care, outpatient hand unit in a
      district general hospital. Three convenience samples of: 59 people with de
      Quervain's disease; 18 with carpal tunnel syndrome (CTS) and 16 with
      osteoarthritis (OA) of the carpometacarpal (CMC) joint were recruited. The DQST
      diagnostic criteria were initially generated from a literature review. Content
      validity was then established by expert doctors with an interest in upper limb
      musculoskeletal disorders (n = 7) rating the relevance of the seven items
      included. The DQST was then tested in people either already diagnosed with, or
      reported as having some of the symptoms of, de Quervain's disease. Construct
      validity was tested with people with CTS or OA of the CMC joint. RESULTS: The
      median DQST score was 5 (Interquartile range IQR = 4-6) out of a possible seven
      diagnostic criteria. Inter-rater reliability was excellent (Intra-class
      coefficient [ICC] = 0.85; 95% confidence interval [CI] = 0.75, 0.91). Test retest
      reliability was good (ICC = 0.64; 95% CI = 0.20, 0.87). Sensitivity (Se) and
      specificity (Sp) testing (Se = 1.00; Sp = 1.00) demonstrated that the DQST
      discriminated between people with de Quervain's disease, CTS or OA of the CMC
      joint. CONCLUSIONS: The DQST is a valid, reliable tool which could be of
      assistance in aiding correct diagnosis for recruitment to clinical trials and in
      clinical practice. Future research is recommended to further examine retest
      reliability with a larger sample size and to identify the commonest diagnostic
      criteria required for inclusion.

PMID- 18618463
TI  - An acylated flavonol glycoside and hydrolysable tannins from Callistemon
      lanceolatus flowers and leaves.
AB  - INTRODUCTION: Callistemon lanceolatus DC. (Myrtaceae) is a plant rich in
      polyphenols, and is used as anticough, antibronchitis and insecticide in folk
      medicine. Because of the biological importance of plant polyphenols, particularly
      tannins, a phytochemical study was of interest to investigate the constitutive
      poyphenols in the extracts of flowers and leaves. OBJECTIVE: To avoid time
      consuming methodology for isolation of a complex mixture of known metabolites,
      HPLC-ESI/MS was employed for fast picking up of the new compounds followed by
      identification of the structures with UV and one- and two-dimensional NMR.
      METHODOLOGY: Flowers and leaves were separately extracted with hot aqueous
      methanol under reflux (70 degrees C). Pre-isolation of the total extracts was
      achieved through column chromatographic fractionation on polyamide with water
      methanol for gradient elution. The main fractions were purified using repeated
      column chromatography on cellulose and/or Sephadex LH-20 with suitable eluents.
      HPLC-ESI/MS analyses were carried out in the single ion monitoring (SIM) and
      negative ion modes. The pure compounds in methanol-water (1:1) were analysed by
      direct infusion ESI/MS. Final structure elucidation was obtained by one- and two
      dimensional NMR. RESULTS: Two new metabolites namely quercetin 3-O-beta-D
      glucuronopyranoside n-butyl ester (1) and n-butylgallate 4-O-(2',6'-di-O-galloyl)
      beta-D-glucopyranoside (4) along with nine known ones were identified from the
      aqueous methanol extracts of flowers and leaves. CONCLUSION: The study has shown
      that Callistemon lanceolatus is rich in polyphenols. HPLC-ESI/MS may be used, in
      negative ion mode, as an efficient and rapid analytical tool for investigating
      complex plant extracts.

PMID- 18618464
TI  - Evaluation of protein, peptide, and amino acid retention on C5 hydride-based
      stationary phases.
AB  - A pentyl (C5) stationary phase is synthesized on a hydride surface using both 100
      and 300 A silica particles. The aqueous normal phase properties of these new
      phases are evaluated using amino acids at high concentrations of ACN in the
      mobile phase containing 0.1% formic acid. The RP properties of the materials are
      tested by using peptides and proteins in order to evaluate the effect of pore
      size on retention. Comparisons of retention as well as efficiencies and peak
      symmetry with a C18 phase are used to determine the influence of the hydrophobic
      properties of the bonded material. An evaporative light scattering detector
      (ELSD) is used in all phases of the study and compared with UV detector for
      gradient elution of proteins.

PMID- 18618465
TI  - Determination of volatile and non-volatile products of milk fermentation
      processes using capillary zone electrophoresis and solid phase microextraction
      coupled to gas chromatography.
AB  - The aim of the investigations was to develop analytical methods for the
      determination of selected volatile and non-volatile organic compounds numbering
      among the final products of milk fermentation. The analyzed compounds were as
      follows: biacetyl and carboxylic acids (formic, acetic, citric, and lactic). The
      model yogurt was prepared under controlled conditions in our laboratory by
      addition of the selected bacteria (Lactobacillus bulgaricus and Streptococcus
      thermophilus) to the milk sample. The temperature, time, and stirring were
      controlled during the fermentation process. Factors considered in SPMPE-GC-FID
      method development included fiber exposure time, salt addition, temperature of
      extraction, and temperature of desorption. Various SPME fibers, for example with
      PDMS, CAR/PDMS, PA, and PDMS/DVB coatings, were tested to obtain the highest
      recovery of the investigated compounds extracted from yogurt samples. Based on
      these preliminary experiments, qualitative and quantitative analyses for the
      determination of biacetyl were performed by SPME-GC-FID. Moreover, a capillary
      zone electrophoresis method was developed for the determination of carboxylic
      acids in the yogurt samples. The buffer composition as well as deproteinization
      by acetonitrile were found to have a crucial effect on the analysis.

PMID- 18618466
TI  - Chitosan-NAC nanoparticles as a vehicle for nasal absorption enhancement of
      insulin.
AB  - The purpose of this work was to investigate chitosan-N-acetyl-L-cysteine
      (chitosan-NAC) nanoparticles as a potential carrier system for the nasal delivery
      of insulin. For the study, we used insulin-loaded chitosan-NAC nanoparticles (140
      210 nm in diameter) prepared by in situ gelation with tripolyphosphate (TPP),
      with positive zeta potential values of +19.5-31.7 mV and insulin loading
      capacities of 13-42%. The physicochemical properties of the nanoparticles were
      affected by the number of thiol groups present. Mucoadhesive properties, which
      were evaluated by measuring the in vitro absorbed mass of mucin, of chitosan-NAC
      nanoparticles were >1.8-fold that of unmodified chitosan nanoparticles. In
      aqueous solution, chitosan-NAC nanoparticles exhibited fast swelling behavior.
      Insulin was released from chitosan-NAC nanoparticles in vitro in an initial burst
      followed by slow release. Intranasal administration of chitosan-NAC nanoparticles
      in rats enhanced the absorption of insulin by the nasal mucosa compared with
      unmodified chitosan nanoparticles and control insulin solution. In light of these
      observations, the novel thiolated chitosan nanoparticles represent a promising
      vehicle for nasal insulin administration.

PMID- 18618467
TI  - HPLC analysis of eluted monomers from two composite resins cured with LED and
      halogen curing lights.
AB  - This study investigated the leaching of monomers (Bis-GMA and TEGDMA) from nano
      hybrid (Filtek Supreme) and flowable (Filtek Flow) dental composite resins cured
      with LED or conventional halogen curing lights, and immersed in saliva or water
      for 24 h. Nine disc specimens were made for each experimental group. After the
      polymerization process, the specimens were immersed in either water or saliva and
      incubated at 37 degrees C for 24 h. Eluted Bis-GMA and TEGDMA monomers were
      detected using high performance liquid chromatography (HPLC). The data were
      analyzed using three-way ANOVA (p = 0.05) and the independent samples t test.
      TEGDMA (53.15-1 microg/L) was leached from the resins at a higher level than Bis
      GMA (28-0.5 microg/L) (p < 0.01), regardless of the affecting factors: composite
      type, solvent (media) and type of curing light. In general, Filtek Flow resin
      released more TEGDMA than Filtek Supreme (p < 0.05), but the Supreme resin
      released more Bis-GMA than TEGDMA (p < 0.05). Halogen light induced greater
      monomer elution than LED light immersion in water. Saliva released more TEGDMA
      than water (p < 0.05). We conclude that (1) total leached TEGDMA was higher than
      total Bis-GMA, (2) saliva and halogen light (lower intensity than LED) leached
      more monomers from the resins, and (3) the flowable composite resin leached more
      TEGDMA than the nano-hybrid.

PMID- 18618468
TI  - Separation of inorganic anions on a high capacity porous polymeric monolithic
      column and application to direct determination of anions in seawater.
AB  - A commercially available 4.6 mm id x 50 mm polymethacrylate-based monolithic
      strong anion exchange column (ProSwift SAX-1S) designed for the separation of
      proteins has been successfully used to separate small inorganic anions in the
      presence of a seawater sample matrix. Using a hydroxide eluent with suppressed
      conductivity detection the ion exchange capacity of this column declined over
      time; however, using KCl as the eluent, the column performance was stable with a
      capacity of 530 microequiv. for nitrate. The optimum conditions for the
      separation of iodate, bromate, nitrite, bromide and nitrate were assessed by
      constructing van Deemter plots using 1.00 and 0.100 M KCl. Efficiencies of up to
      26 700 plates/m were recorded using 1.00 M KCl, at a flow rate of 0.20 mL/min but
      iodate was not baseline resolved from the void peak. By reducing the
      concentration of the eluent to 0.100 M, efficiencies of up to 39 900 plates/m
      could be obtained at 0.35 mL/min. By employing a linear gradient ranging from
      0.05 to 1.00 M KCl the ions dissolved in distilled water or a salt water matrix
      could be baseline separated in less than 3 min at a flow rate of 2.50 mL/min.

PMID- 18618469
TI  - Detecting pM concentrations of prostaglandins in cell culture supernatants by
      capillary SCX-LC-MS/MS.
AB  - A highly sensitive, improved online strong cation exchange (SCX)--RP capillary
      liquid chromatographic (cLC) method with IT mass spectrometric (IT-MS/MS)
      detection for the simultaneous determination of prostaglandin (PG)A(1), PGD(2),
      PGE(1), PGE(2), PGF(2alpha), 8-iso-(8i)PGF(2alpha), 6-keto-(6k)PGF(1alpha), and
      15-Delta(12, 14)-deoxy-PGJ(2) (15dPGJ(2)) in cell culture supernatants was
      developed and validated. Pretreatment of the cell culture supernatants included
      only dilution and filtration, and the analysis time including all sample
      preparation steps was 60 min per sample. Peptides/proteins contained in the
      matrix were removed by the SCX column. LODs in the range of 8-44 pg/mL (25-120
      pM) cell culture supernatant were obtained. Excellent linearity (R(2) > 0.99) and
      satisfactory recoveries and within- and between-day precisions were obtained.
      Human mesenchymal stem cells (hMSCs) were stimulated with tumor necrosis factor
      alpha (TNFalpha) or TNFalpha/IL-17, and PG production was analyzed using the
      developed method. The four PGs, 6kPGF(1a), PGF(1a), PGE(2), and PGE(1 )were
      detected both in nonstimulated and stimulated cells. The amount of PG produced by
      the cell increased when the cell was stimulated.

PMID- 18618470
TI  - Capillary electrophoresis of some free fatty acids using partially aqueous
      electrolyte systems and indirect UV detection. Application to the analysis of
      oleic and linoleic acids in peanut breeding lines.
AB  - This study has shown for the first time the suitability of CE with a partially
      aqueous electrolyte system for the analysis of free fatty acids (FFAs) in small
      portions of single peanut seeds. The partially aqueous electrolyte system
      consisted of 40 mM Tris, 2.5 mM adenosine-5'-monophosphate (AMP) and 7 mM alpha
      CD in (N-methylformamide) NMF/dioxane/water (5:3:2 by volume) mixture, pH 8-9.
      While AMP served as the background UV absorber for indirect UV detection of the
      FFAs, the alpha-CD functioned as the selectivity modulator by affecting the
      relative effective electrophoretic mobilities of the various FFAs due to their
      differential association with alpha-CD. This CE method allowed the screening of
      peanut seeds for their content of oleic and linoleic acids, which is essential in
      breeding of peanuts of high-oleic acid content. The extraction method of FFAs
      from peanut seeds is very reproducible with a high recovery approaching
      quantitative yield (approximately 97% recovery).

PMID- 18618471
TI  - Structure and performance of silica-based monolithic HPLC columns.
AB  - Silica-based monolithic columns were prepared for HPLC with systematic variations
      of the tetramethoxysilane (TMOS) and polyethylene oxide (PEO) content as
      reactants in a sol-gel process accompanied by phase separation. The resulting
      monoliths showed differences in the macropore and silica skeleton diameter as
      well as in the corresponding domain sizes (the sum of macropore and skeleton
      diameter). All monoliths were synthesized with a diameter of 4.6 mm and cladded
      with a suitable polyaryletheretherketone (PEEK) polymer in a standardized and
      optimized manner for the subsequent chromatographic evaluation of the resulting
      monolithic HPLC columns. The columns were tested under normal phase conditions
      using n-heptane/dioxane (95:5 v/v) as a mobile phase and 2-nitroanisole as a test
      compound for the determination of separation efficiency and permeability. Two
      different sets of columns were prepared: the first one in which the amount of PEO
      was stepwise decreased to yield monoliths with identical macropore volumes and
      variations in the domain sizes. The second group of materials was synthesized
      adjusting both TMOS and PEO quantities to yield monolithic columns with identical
      macropore diameters of about 1.80 microm but different skeleton diameters and
      macropore volumes. The chromatographic results suggest that an increase in the
      column performance cannot be achieved by just arbitrarily decreasing the domain
      size of a given column. From a certain point of "downsizing" the monolithic
      structure a loss of structural homogeneity can be observed, which is apparently
      responsible for a lower chromatographic performance.

PMID- 18618472
TI  - Coated-wall microreactor for continuous biocatalytic transformations using
      immobilized enzymes.
AB  - Microstructured flow reactors are emerging tools for biocatalytic process
      development. A compelling design is that of the coated-wall reactor where enzyme
      is present as a surface layer attached to microchannel walls. However,
      preparation of a highly active wall biocatalyst remains a problem. Here, a
      stainless steel microreactor was developed where covalent immobilization of the
      enzyme in multiple linear flow channels of the reaction plate was supported by a
      macroporous wash-coat layer of gamma-aluminum oxide. Using surface
      functionalization with aminopropyl triethoxysilane followed by activation with
      glutardialdehyde, the thermophilic beta-glycosidase CelB from Pyrococcus furiosus
      was bound with retention of half of the specific activity of the free enzyme (800
      U/mg), yielding a high catalyst loading of about 500 U/mL. This microreactor was
      employed for the continuous hydrolysis of lactose (100 mM) at 80 degrees C,
      providing a space-time yield of 500 mg glucose/(mL h) at a stable conversion of >
      or =70%. The immobilized enzyme displayed a half-life of 15 days under the
      operational conditions. Due to the absence of hydrophobic solute-material
      interactions, which limit the scope of microstructures fabricated from
      poly(dimethylsiloxane) for biocatalytic applications, the new microreactor was
      fully compatible with the alternate enzyme substrate 2-nitro-phenyl-beta-D
      galactoside and the 2-nitro-phenol product resulting from its hydrolysis
      catalyzed by CelB.

PMID- 18618473
TI  - Chemical fingerprinting of Lawsonia inermis L. using HPLC, HPTLC and
      densitometry.
AB  - INTRODUCTION: Lawsonia inermis L. is a natural red colouring agent, commonly
      named "Henna", which is used to dye skin and hair. The aim of this study was to
      evaluate the quality of L. inermis that is commercially available as a raw plant
      material or preparation in order to guarantee good quality products. OBJECTIVE:
      To develop a simple protocol for the qualification of different samples labelled
      as L. inermis by using the HPTLC densitometry method and to identify possible
      adulterations with other plants. METHODOLOGY: Samples of leaves of L. inermis
      were extracted with methanol. Two chromatographic methods were developed to
      determine the chemical fingerprinting of L. inermis. The first was based on HPTLC
      identification followed by densitometric measurements at 337 nm. The second was
      based on RP-HPLC separation with gradient elution and photodiode array detection
      at 337 nm. Samples of Cassia obovata Collad., and Indigofera tinctoria L., were
      treated in the same way. RESULTS: The simplicity of the sample preparation, and
      the possibility of analysing several samples of herbal products simultaneously in
      a short time, make HPTLC the method of choice. The HPTLC method was feasible for
      the comprehensive quality evaluation of herbal products. From the comparison of
      their "fingerprint", it was possible to detect substitution of plants that are
      different from those declared on the label. CONCLUSION: The HPTLC may be used as
      a rapid method by which to control the quality of raw plant materials and
      formulations based on the title plant.

PMID- 18618475
TI  - Triage for surgical management of ovarian tumors in asymptomatic women:
      assessment of an ultrasound-based scoring system.
AB  - OBJECTIVES: To prospectively evaluate an ultrasound-based scoring system as a
      method for triaging asymptomatic women presenting with an adnexal mass for
      surgical treatment. METHODS: Two hundred and four adnexal masses in 189
      asymptomatic women undergoing elective surgical treatment at our institution were
      included in this prospective study. Patients were evaluated by transvaginal power
      Doppler ultrasound imaging before surgery. Patients were classified as low risk
      or high risk for malignancy according to an ultrasound-based scoring system.
      Women with a low risk for malignancy were scheduled for laparoscopy and patients
      with a high risk for malignancy were scheduled for laparotomy. However, patients
      classified as low risk by the ultrasound scoring system, but with a tumor size
      >or= 10 cm or clinical suspicion of pelvic adhesions, were instead considered to
      be at intermediate risk and were scheduled for laparotomy. Some patients
      classified as high risk were scheduled for an operative laparoscopy by an expert
      in gynecological oncology. RESULTS: One hundred and thirty-four (65.7%) masses
      were considered to be low risk and were treated by a laparoscopically guided
      procedure. All these tumors were benign. Forty-seven (23%) masses were classified
      as high risk, of which 39 tumors were malignant and eight benign. Twenty-three
      (11.3%) tumors were considered to be intermediate risk and were scheduled for
      primary laparotomy. In this group, 21 (91.3%) tumors proved to be benign and two
      (8.7%) were malignant. CONCLUSIONS: Ultrasound-based triage of asymptomatic women
      diagnosed with a persistent adnexal mass is effective for selecting the surgical
      approach.

PMID- 18618474
TI  - Study on the extraction, purification and quantification of jasmonic acid,
      abscisic acid and indole-3-acetic acid in plants.
AB  - INTRODUCTION: Jasmonic acid (JA), abscisic acid (ABA) and indole-3-acetic acid
      (IAA) are important plant hormones. Plant hormones are difficult to analyse
      because they occur in small concentrations and other substances in the plant
      interfere with their detection. OBJECTIVE: To develop a new, inexpensive
      procedure for the rapid extraction and purification of IAA, ABA and JA from
      various plant species. METHODOLOGY: Samples were prepared by extraction of plant
      tissues with methanol and ethyl acetate. Then the extracts were further purified
      and enriched with C(18) cartridges. The final extracts were derivatised with
      diazomethane and then measured by GC-MS. The results of the new methodology were
      compared with those of the Creelman and Mullet procedure. RESULTS: Sequential
      elution of the assimilates from the C(18 )cartridges revealed that IAA and ABA
      eluted in 40% methanol, while JA subsequently eluted in 60% methanol. The new
      plant hormone extraction and purification procedure produced results that were
      comparable to those obtained with the Creelman and Mullet's procedure. This new
      procedure requires only 0.5 g leaf samples to quantify these compounds with high
      reliability and can simultaneously determine the concentrations of the three
      plant hormones. CONCLUSION: A simple, inexpensive method was developed for
      determining endogenous IAA, ABA and JA concentrations in plant tissue.

PMID- 18618476
TI  - Surface AFM microscopy of unworn and worn samples of silicone hydrogel contact
      lenses.
AB  - PURPOSE: To evaluate the qualitative and quantitative topographic changes in the
      surface of worn contact lenses (CLs) of different materials using atomic force
      microscopy (AFM). METHODS: The topography of five different CL materials was
      evaluated with AFM over a surface of 25 microm(2) according to previously
      published experimental setup. Average roughness (R(a)) and root mean square (Rms)
      values were obtained for unworn and worn samples. RESULTS: The R(a) value
      increased for balafilcon A (11.62-13.68 nm for unworn and worn samples,
      respectively), lotrafilcon A (3.67-15.01 nm for unworn and worn samples,
      respectively), lotrafilcon B (4.08-8.42 nm for unworn and worn samples,
      respectively), galyfilcon A (2.81-14.6 nm for unworn and worn samples,
      respectively), and comfilcon A (2.87-4.63 nm for unworn and worn samples,
      respectively). Differences were statistically significant for all lenses except
      Rms and R(a) for comfilcon A, and R(a) parameter for balafilcon A (p > 0.05). The
      least relative increase was observed for some balafilcon A samples and for some
      of these samples the roughness decreased after the lenses had been worn.
      CONCLUSION: The changes in surface roughness between unworn and worn lenses are
      different for different silicone-hydrogel materials. Overall all CLs increased
      the degree of surface roughness after being worn, even for very short periods of
      time. However, for samples of balafilcon A, roughness increases at a lower extent
      or even can decrease as compared to unworn samples of the same material due to
      filling of the macropores.

PMID- 18618477
TI  - In vivo assessment of herb-drug interactions: possible utility of a
      pharmacogenetic approach?
AB  - Herbal medicines are frequently used in combination with conventional drugs and
      interactions are likely to be more common than those which manifest clinically.
      Pharmacokinetic interactions mediated by drug-metabolizing enzymes or
      transporters are involved in many herb-drug interactions. Polymorphisms in the
      genes for these enzymes and transporters may influence the interactions mediated
      through these pathways. Herb-drug interactions can be identified in vivo using
      the herbs with individual probe drugs or drugs with a narrow therapeutic index. A
      probe drug cocktail approach offers a more efficient screening procedure. If
      potential interactions are studied in subject groups with different genotypes,
      more definitive information can be obtained. The selection of genotype groups to
      study should depend not only on the major enzymes or transporters involved in the
      disposition of a drug, but also on alternate pathways which may become more
      important in subjects with reduced activity in the primary pathway, and the
      pathways for pharmacodynamic effects should also be considered for some drugs.
      Some genotypes may only be found in certain ethnic groups. Currently, the
      pharmacogenetic approach has been used mainly to study drug-drug interactions so
      there is considerable potential to extend this to the study of herb-drug
      interactions in vivo.

PMID- 18618478
TI  - The influence of metabolism on the genotoxicity of catechol estrogens in three
      cultured cell lines.
AB  - The 2- and 4-hydroxy metabolites of 17beta-estradiol (E2) and estrone (E1) are
      important for E2-mediated carcinogenesis due to the formation of genotoxic ortho
      quinone metabolites. To assess the importance of metabolic conjugation for their
      genotoxicity, the DNA strand-breaking activity of the four catechol estrogens was
      determined in three cell lines with different activities of catechol-O
      methyltransferase (COMT) and UDP-glucuronosyltransferase (UGT). Most DNA strand
      breaks were observed in V79 cells, which lack these metabolic activities. 2- and
      4-hydroxy-E2 were 2.5 times more genotoxic than 2- and 4-hydroxy-E1. MCF-7 cells
      exhibit COMT activity, and the incidence of DNA strand breaks decreased with
      increasing methylation; only the 4-hydroxy metabolites of E1 and E2, which were
      poor substrates of COMT, exhibited low genotoxicity. HepG2 cells converted the
      catechol and methoxy metabolites of E2 to the respective E1 metabolites by 17beta
      hydroxysteroid dehydrogenase (HSD). Moreover, methylation and glucuronidation
      took place. Only 4-hydroxy-E1 elicited a weak genotoxic response in these cells.
      The extensive metabolism in HepG2 cells is proposed to account for the failure of
      catechol estrogens to induce DNA strand breaks. Thus, metabolism by COMT and UGT
      and, to a minor extent, by HSD is a major determinant for the genotoxicity of
      catechol estrogens in target cells.

PMID- 18618479
TI  - Model experiments mimicking the human intestinal transit and metabolism of D
      galacturonic acid and amidated pectin.
AB  - In order to study the human intestinal transit and metabolism of D-galacturonic
      acid and amidated pectin a number of model experiments were carried out. Both
      substrates were incubated under aerobic conditions at 37 degrees C using saliva
      (2 min) and simulated gastric juice (4 h). Under anaerobic conditions the
      substrates were incubated at 37 degrees C using human ileostomy and colostomy
      fluids, each obtained from three different donors, for 10 and for 24 h,
      respectively. D-Galacturonic acid, SCFA (acetic acid, propionic acid, and butyric
      acid), as well as methanol were analyzed photometrically after carbazole
      reaction, GC-flame ionization detection (GC-FID), and headspace solid-phase
      microextraction GC/MS (HS-SPME-GC/MS), respectively. D-Galacturonic acid and
      amidated pectin were found to be stable during incubations with saliva and
      simulated gastric juice, whereas both substrates underwent degradation in the
      course of human ileostomy and colostomy fluid incubations. D-Galacturonic acid
      was practically completely decomposed within 10 h and SCFA, with acetic acid as
      the major representative, were formed up to 98% of the incubated substrate in
      colostomy effluent. The amidated pectin was only degraded in part, revealing
      stable amounts of 22-35% and 3-17% in ileostomy (after 10 h) and colostomy fluid
      (after 24 h), respectively. SCFA were generated up to 59% of the applied amidated
      pectin. In parallel, 19-60% and 52-67% of the available methyl ester groups were
      cleaved in the course of incubations with ileostomy and colostomy fluids,
      respectively. The results demonstrate for the first time that D-galacturonic acid
      and amidated pectin are stable in human saliva and simulated gastric juice. The
      degradation of both compounds during incubation with ileostomy effluent is
      highlighted, providing evidence for a considerable metabolic potential of the
      small intestine.

PMID- 18618480
TI  - 25 years food chemistry and toxicology at the University of Kaiserslautern.

PMID- 18618481
TI  - A critical evaluation of drug interactions with Echinacea spp.
AB  - Accurate information concerning drug-herb interactions is vital for both
      healthcare providers and patients. Unfortunately, many of the reviews on drug
      herb interactions contain overstated or inaccurate information. To provide
      accurate information on drug-herb interactions healthcare providers must account
      for product verification, dosage, medicinal plant species, and plant part used.
      This critical review assessed the occurrence of drug interactions with one of the
      top selling botanical remedies, echinacea including Echinacea angustifolia, E.
      pallida, and E. purpurea. Only eight papers containing primary data relating to
      drug interactions were identified. Herbal remedies made from E. purpurea appear
      to have a low potential to generate cytochrome P450 (CYP 450) drug-herb
      interactions including CYP 450 1A2 (CYP1A2) and CYP 450 3A4 (CYP3A4). Currently
      there are no verifiable reports of drug-herb interactions with any echinacea
      product. However, further pharmacokinetic testing is necessary before conclusive
      statements can be made about echinacea drug-herb interactions. Given our
      findings, the estimated risk of taking echinacea products (1 in 100,000), the
      number of echinacea doses consumed yearly (> 10 million), the number of adverse
      events (< 100) and that the majority of use is short term, E. purpurea products
      (roots and/or aerial parts) do not appear to be a risk to consumers.

PMID- 18618482
TI  - Effects of the mycotoxin deoxynivalenol on human primary hepatocytes.
AB  - Toxic effects of the mycotoxin deoxynivalenol (DON) observed in animals range
      from diarrhea, vomiting, gastro-intestinal inflammation to necrosis of several
      tissues. In the last years, DON has been tested in hepatocytes of several animal
      species for its cytotoxicity. However, these tests are limited to the use of
      animal cells. No studies using human hepatocytes are available. Further
      investigations with the human hepatocellular liver carcinoma cell line HepG2
      might be limited due to the disadvantages of cell lines (e. g. immortalization,
      tumor derivation, longtime cultivation) and do not necessarily reflect the
      response of normal human cells. In order to overcome this problem and to be
      closer to the human situation, we studied the effect of DON in human primary
      hepatocytes and compared these data to the effects in the HepG2 cell line. Cell
      viability, apoptotic and necrotic cell death, albumin secretion and metabolic
      activity were determined. It could be demonstrated that DON has a distinct
      cytotoxic effect on human primary hepatocytes. Viability, protein content and
      albumin secretion were reduced in a dose-dependent manner. The apoptotic key
      enzyme caspase-3 was activated, while LDH release occurred only after long
      incubation time due to a secondary necrosis. Furthermore, we studied the
      metabolism of DON using LC-MS/MS. DON was neither metabolized by primary
      hepatocytes cells nor by the HepG2 cell line.

PMID- 18618483
TI  - A transformation procedure for recalcitrant tomato by addressing transgenic plant
      recovery limiting factors.
AB  - Agrobacterium tumefaciens technology is the battle horse for tomato genetic
      transformation. However, tomato varieties with low regeneration capacity are very
      difficult to transform. In the past, tomato transformation through Agrobacterium
      infection was focused on varieties capable of high regeneration yield, while
      successful transformation of low regenerable cultivars has not been reported. The
      genotype response to tissue culture conditions is believed to drive the frequency
      of regeneration of transgenic plant, whereas the capacity for cell proliferation
      could determine the transformation efficiency through this technology. The
      Campbell-28 cultivar is an example of constraints arising from a high
      morphogenetic potential with low conversion compared to normal plants. In the
      present work the roles that contribute to improved transgenic plant recovery from
      this recalcitrant variety were explored for factors like Agrobacterium
      concentration and antibiotics for bacterial removal and transformant selection.
      Analysis of the efficiency from independent transformation experiments revealed a
      more than twofold increase of transformant regeneration after selection on
      ammonium glufosinate compared to kanamycin selection, showing a transformation
      efficiency of 21.5%.

PMID- 18618484
TI  - Increasing cell adhesion on plasma deposited fluorocarbon coatings by changing
      the surface topography.
AB  - In designing new biomaterials, it is of outstanding importance to consider how
      cells respond to specific chemical and topographical features on the material
      surface. The behavior of most cell types in vivo is strictly related to specific
      chemical and topographical cues that characterize the extra cellular environment.
      In particular, during their lives cells react to topographical patterns such as
      those of the extracellular matrix (ECM), of micro and/or nanometric dimensions.
      The production of micrometric and/or nanometric features on artificial materials
      usually involves expensive and time-consuming methods of manufacturing, such as
      electron beam and colloidal lithography. In this article, different "Teflon-like"
      structured surfaces were deposited from tetrafluoroethylene (C(2)F(4))-fed
      plasmas, for the study of cell adhesion and growth. The reaction of different
      cell lines to different topographical features was evaluated and compared with
      cell behavior on flat samples with the same chemical composition. Cell adhesion
      was calculated from area covered by cells at different time of culture. Beside
      this, cell proliferation was determined with the MTT test. Cell morphology and
      filopodia interaction with the nanofeatures were also estimated by optical and
      scanning electron microscopy. A dramatic difference both in adhesion and growth
      was found between cells seeded on flat and rough surfaces with the density and
      spreading of adhered cells varying as a function of the roughness of coatings.

PMID- 18618485
TI  - Comparison of delphinidin, quercetin and (-)-epigallocatechin-3-gallate as
      inhibitors of the EGFR and the ErbB2 receptor phosphorylation.
AB  - In the present study, delphinidin was found to suppress the phosphorylation of
      the epidermal growth factor receptor (EGFR) within human tumour cells (human
      colon carcinoma cell line (HT29), human vulva carcinoma cell line (A431)), albeit
      less effective than the flavonol quercetin. The higher potency of quercetin was
      also observed downstream on the level of the mitogen-activated protein kinase
      (MAPK) cascade. In addition, delphinidin, quercetin and (-)-epigallocatechin-3
      gallate (EGCG) were found to suppress the phosphorylation of the ErbB2 receptor,
      with delphinidin exhibiting the strongest inhibitory properties. Their potency to
      suppress the ErbB2 receptor phosphorylation can be summarised as delphinidin >
      EGCG > quercetin. The effectiveness of delphinidin against the EGFR and the ErbB2
      receptor was comparable, indicating a broader spectrum of activity against
      receptor tyrosine kinases. At low micromolar concentrations delphinidin showed
      some preference towards the ErbB2 receptor. In summary, quercetin and delphinidin
      appear to differ in their activity profile towards the ErbB receptor family
      members. Whereas quercetin was most effective against the EGFR, delphinidin
      exhibited some preference towards the ErbB2 receptor.

PMID- 18618486
TI  - Synthesis and cytotoxicity testing of novel 2-(3-substituted-6-chloro-1,1-dioxo
      1,4,2-benzodithiazin-7-yl)-3-phenyl-4(3H)-quinazolinones.
AB  - A new series of thirteen 2-[3-(substituted amino)-6-chloro-1,1-dioxo-1,4,2
      benzodithiazin-7-yl]-3-phenyl-4(3H)-quinazolinones 4-16 were prepared in order to
      evaluate their cytotoxic activity against 12 human cancer cell lines. The
      bioassay indicated that the quinazolinone derivatives 5, 8-12, 15, and 16 possess
      cancer-cell growth-inhibitory properties. Compounds 5 and 12 showed a high level
      of selectivity for certain cell lines. The most active compounds 9, 10, 15, and
      16 showed moderate antiproliferative activity and were approximately 4-fold less
      potent than cisplatin.

PMID- 18618487
TI  - Structural modifications of salicylates: inhibitors of human CD81-receptor HCV-E2
      interaction.
AB  - Starting point of the present paper was the result of a virtual screening using
      the open conformation of the large extracellular loop (LEL) of the CD81-receptor
      (crystal structure: PDB-ID: 1G8Q). After benzyl salicylate had been
      experimentally validated to be a moderate inhibitor of the CD81-LEL-HCV-E2
      interaction, further optimization was performed and heterocyclic-substituted
      benzyl salicylate derivatives were synthesized. The compounds were tested for
      their ability to inhibit the interaction of a fluorescence-labeled antibody to
      CD81-LEL using HUH7.5 cells. No compound showed an increase concerning the
      inhibition of the protein-protein interaction compared to benzyl salicylate.

PMID- 18618488
TI  - Total synthesis and biological potential of psammosilenin A.
AB  - The present work reports the synthesis of a plant-originated cyclooctapeptide-
      psammosilenin A 8--by cyclization of linear peptide fragment phe-pro-phe-phe-ala
      pro-leu-pro-Opfp which was prepared by coupling of tetrapeptide units Boc-phe-pro
      phe-phe-OH and ala-pro-leu-pro-OMe followed by proper deprotection of terminal
      groups and activation of the acid functionality. During synthesis,
      dicyclohexylcarbodiimide (DCC) and N,N-diisopropylcarbodiimide (DIPC) were used
      as the coupling agents and N-methylmorpholine (NMM)/triethylamine (TEA) were used
      as bases. Structure of the synthesized peptide was elucidated by spectral as well
      as elemental data. The newly synthesized peptide was subjected to biological
      screening and found to possess potent cytotoxic activity against DLA and EAC cell
      lines with IC(50) value of 7.93 and 17.06 microM, respectively. Furthermore, good
      anthelmintic activity against earthworms M. konkanensis and Eudrilus species at 1
      and 2 mg/mL was also observed for the synthesized cyclic peptide. Studies
      indicated that N-methylmorpholine was a more useful base for cyclization of
      linear peptide unit in comparison to pyridine.

PMID- 18618489
TI  - Synthesis and in-vitro antibacterial activity of 5-substituted 1-methyl-4-nitro
      1H-imidazoles.
AB  - A series of 5-substituted 1-methyl-4-nitro-1H-imidazole derivatives were
      synthesized and evaluated for in-vitro antibacterial activity against a panel of
      microorganisms including Staphylococcus aureus, Staphylococcus epidermidis,
      Bacillus subtilis, Escherichia coli, Klebsiella pneumonia, Enterobacter
      aerogenes, and Helicobacter pylori using conventional agar dilution method. Among
      the test compounds, 1-methyl-4-nitro-5-(phenylsulfonyl)-1H-imidazole was the most
      potent against Gram-positive bacteria, with a MIC value of < or =8 microg/mL. All
      compounds showed no significant activity against Gram-negative bacteria at
      concentrations < or =64 microg/mL. The MIC values against 15 clinical isolates of
      H. pylori indicated that compounds 10 and 11 were the most active compounds in
      this series in terms of inhibiting the growth of H. pylori (MIC = 2 microg/mL).
      It was also demonstrated that their corresponding activities were four times
      larger than that of metronidazole.

PMID- 18618490
TI  - Synthesis and evaluation of the luciferase-oligodeoxynucleotide for the sequence
      selective detection of nucleic acids.
AB  - A new method for the synthesis of ODN-luciferase conjugate was investigated as a
      signal-amplifying sensor of the target nucleic acids. The conjugation of the
      luciferase was successfully achieved between the cysteine residue and the 2-amino
      6-vinylpurine nucleoside of the ODN probe without significant inactivation of
      luciferase. The ODN-luciferase conjugate modified with PEG retained the
      luciferase activity and selectivity during the hybridization with the target ODN.

PMID- 18618491
TI  - Synthesis of nitroxyl radicals for Overhauser-enhanced magnetic resonance
      imaging.
AB  - Non-invasive measurement and visualization of free radicals in vivo would be
      important to clarify their roles in the pathogenesis of free radical-associated
      diseases. Nitroxyl radicals can react with free radicals and be derivatized to
      achieve specific cellular/subcellular localizing capabilities while retaining the
      simple spectral features useful in imaging. Overhauser-enhanced magnetic
      resonance imaging (OMRI), which is a double resonance technique, creates images
      of free radical distributions in small animals by enhancing the water proton
      signal intensity via the Overhauser Effect. In this study, we synthesized various
      nitroxyl probes having (15)N nuclei and deuterium, and measured the enhancement
      factor for Overhauser-enhanced magnetic resonance imaging experiments. (15)N-D-4
      Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl ((15)N-D-oxo-TEMPO) has the highest
      enhancement factor compared with other nitroxyl probes. The proton signal
      enhancement was higher for (15)N-labeled nitroxyl probes when compared to the
      (14)N-labeled analogues because of the reduced spectral multiplicity of the I=1/2
      nucleus. Furthermore, this enhancement is proportional to the line width and
      number of electron spin resonance lines of nitroxyl radicals. Finally, we
      compared the Overhauser-enhanced magnetic resonance image of (15)N-labeled,
      deuterated 4-Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl with that of (14)N-H
      TEMPOL. These results suggested that the selective deuteration of the nitroxyl
      probes enhanced the signal-to-noise ratio and thereby improved spatial and
      temporal resolutions.

PMID- 18618492
TI  - 3C-SiC nanocrystals as fluorescent biological labels.

PMID- 18618493
TI  - Improved image analysis workflow for 2-D gels enables large-scale 2-D gel-based
      proteomics studies--COPD biomarker discovery study.
AB  - 2-D gel electrophoresis has been used for more than three decades to study the
      protein complement of organisms, tissues, and cells. Three issues are holding
      back large-scale proteomics studies: low-throughput, high technical variation,
      and study designs lacking statistical power. We identified image analysis as the
      central factor connecting these three issues. By developing an improved image
      analysis workflow we shortened project timelines, decreased technical variation,
      and thus enabled large-scale proteomics studies that are statistically powered.
      Rather than detecting protein spots on each gel image and matching spots across
      gel images, the improved workflow is based on aligning images first, then
      creating a consensus spot pattern and finally propagating the consensus spot
      pattern to all gel images for quantitation. This results in a data table without
      gaps. As an example we show here a study aimed at discovering circulating
      biomarkers for chronic obstructive pulmonary disease (COPD). Eight candidate
      biomarkers were identified by comparing plasma from 24 smokers with COPD and 24
      smokers without COPD. Among the candidates are proteins such as plasma retinal
      binding protein (RETB) and fibrinogen that had previously been linked to the
      disease and are frequently monitored in COPD patients, as well as other proteins
      such as apolipoprotein E (ApoE), inter-alpha-trypsininhibitor heavy chain H4
      (ITIH4), and glutathione peroxidase.

PMID- 18618494
TI  - Racial/ethnic differences in adequacy of information and support for women with
      breast cancer.
AB  - BACKGROUND: Providing breast cancer patients with needed information and support
      is an essential component of quality care. This study investigated racial/ethnic
      variations in the information received and in the availability of peer support.
      METHODS: In total, 1766 women who were diagnosed with nonmetastatic breast cancer
      and reported to the Los Angeles County Surveillance, Epidemiology, and End
      Results registry from June 2005 to May 2006 were mailed a survey after initial
      treatment. Among accrued cases, 96.2% met eligibility criteria (n = 1698), and
      72% completed the survey. Race/ethnicity categories were white, African American,
      and Latinas (2 categories indicating low or high acculturation, which was
      determined by using the Short Acculturation Scale for Hispanics). Outcomes
      included receipt and need for treatment-related and survivorship-related
      information, difficulty understanding information, and support from women with
      breast cancer. RESULTS: More women reported receiving treatment-related
      information than survivorship-related information. After adjusting for
      sociodemographic, clinical, and treatment factors, a higher percentage of low
      acculturated Latina women desired more information on treatment-related and
      survivorship-related issues (P < .001). Significantly more Latina low
      acculturated women than white women reported difficulty understanding written
      materials, with 74.5% requiring help from others. A higher percentage of all
      minority groups compared with whites reported no contact with other women with
      breast cancer (P < .05) and reported less contact through family/friends (P <
      .05). Women rated the benefit of talking to other women high, particularly with
      emotional issues. CONCLUSIONS: Continued efforts to provide culturally
      appropriate information and support needs to women with breast cancer are
      necessary to achieve quality care. Latinas with low acculturation reported more
      unmet information and care support needs than women in other racial/ethnic
      groups.

PMID- 18618495
TI  - Radioembolization with selective internal radiation microspheres for
      neuroendocrine liver metastases.
AB  - BACKGROUND: There are limited effective treatment options available and a poor 5
      year survival for patients with inoperable neuroendocrine liver metastases
      (NETLMs). In this study, the authors prospectively assessed the safety and
      efficacy of treatment with yttrium 90 ((90)Y) radioactive microspheres for
      patients with unresectable NETLMs. METHODS: Radioactive (90)Y resin microspheres
      (selective internal radiation [SIR-Spheres]) were administered through a
      temporarily placed percutaneous hepatic artery catheter concomitantly with a 7
      day systemic infusion of 5-fluorouracil to patients with progressive,
      unresectable NETLMs. Patients were monitored prospectively, and the response to
      treatment was measured by using cancer markers and tumor size on computed
      tomography imaging studies. RESULTS: Thirty-four patients (22 men) with a mean
      age 61 years (range, 32-79 years) who had unresectable NETLMs were treated
      between December 2003 and December 2005. The mean (+/-standard error) follow-up
      was 35.2 +/- 3.2 months. The site of the primary neuroendocrine tumor was the
      bronchus in 1 patient, the medullary thyroid in 2 patients, gastrointestinal in
      15 patients, the pancreas in 8 patients, and of unknown origin in 8 patients. The
      tumors were classified as vipoma (1 tumor), somatostatinoma (1 tumor),
      glucagonoma (2 tumors), large cell (3 tumors), carcinoid (25 tumors), and of
      unknown origin (2 tumors). Complications after (90)Y radioembolization included
      abdominal pain, which was mild to severe; nausea and fever; and lethargy that
      lasted from 1 week to 1 month. Two patients developed biopsy-proven radiation
      gastritis, 1 patient developed a duodenal ulcer, and there was 1 early death from
      liver dysfunction and pneumonia. Subjective changes from recorded baseline
      hormone symptoms were reported every 3 months. Symptomatic responses were
      observed in 18 of 33 patients (55%) at 3 months and in 16 of 32 patients (50%) at
      6 months. Radiologic liver responses were observed in 50% of patients and
      included 6 (18%) complete responses and 11 (32%) partial responses, and the mean
      overall survival was 29.4 +/- 3.4 months). In patients who had evaluable
      chromogranin A (CgA) marker levels, there was a fall in CgA marker levels after
      (90)Y radioembolization in 19 patients (26%) at 1 month, in 19 patients (41%) at
      3 months, in 15 patients (43%) at 6 months, in 11 patients (42%) at 12 months, in
      8 patients (38%) at 24 months, and in 3 patients (46%) at 30 months. CONCLUSIONS:
      In this open study of 34 patients, the results demonstrated that
      radioembolization with (90)Y resin microspheres can achieve relatively long-term
      responses in some patients with nonresectable NETLMs.

PMID- 18618496
TI  - Sunitinib-induced macrocytosis in patients with metastatic renal cell carcinoma.
AB  - BACKGROUND: Sunitinib and sorafenib are small molecules that inhibit the vascular
      endothelial growth factor and related receptors with substantial clinical
      activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and
      macrocytosis have been described in patients treated with these agents. METHODS:
      A retrospective review of all patients with metastatic RCC who were treated with
      sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig
      Cancer Institute was undertaken. Complete blood count (CBC) data including red
      blood cell indices were recorded at baseline, after 3 months of therapy, and at
      the end of treatment. RESULTS: A total of 61 patients were treated with sunitinib
      and 37 patients were treated with sorafenib with available CBC data. In patients
      treated with sunitinib, the median corpuscular volume (MCV) increased
      significantly at 3 months compared with baseline (median increase of 5.1
      femtoliters [fL]; P < .001) and continued to increase throughout treatment.
      Patients who developed hypothyroidism had a larger MCV increase at 3 months than
      patients who remained euthyroid (P = .06), although macrocytosis was observed in
      patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and
      the MCV decreased in all patients within 2 to 4 months, without further
      intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone
      marrow with trilineage hematopoiesis and no evidence of metastasis. There was no
      evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was
      no change in the MCV for patients treated with sorafenib. CONCLUSIONS:
      Macrocytosis was a common occurrence after treatment with sunitinib but not
      sorafenib in patients with metastatic RCC. Sunitinib-induced macrocytosis is
      reversible with drug discontinuation.

PMID- 18618497
TI  - Hypoxia-regulated protein expression, patient characteristics, and preoperative
      imaging as predictors of survival in adults with glioblastoma multiforme.
AB  - BACKGROUND: Regions of hypoxia within glioblastoma multiforme (GBM) are common
      and may influence a tumor's aggressiveness, response to treatment, and the
      patient's overall survival. In this study, the authors examined 4 markers of
      hypoxia (hypoxia-inducible factor 1 [HIF-1alpha], glucose transporter 1 [GLUT-1],
      vascular endothelial growth factor [VEGF], and carbonic anhydrase 9 [CA IX]),
      cellular proliferation and microvascular density (MVD) indices, extent of
      surgical resection, and preoperative imaging characteristics and compared them
      with the overall survival rates of adults with GBM. METHODS: In this
      retrospective cohort study, patients who had lower grade astrocytomas were
      compared with patients who had GBM to verify that the methods used could
      establish differences between tumor grades. By using preoperative imaging, the
      amount of necrosis was established versus the overall tumor area. The authors
      also compared preoperative images with postoperative images to define the amount
      of tumor resected; and they compared molecular markers, proliferation, MVD, and
      imaging studies with survival among patients who had GBM. RESULTS: The hypoxia
      regulated molecules (HRMs) and indices for MVD and cellular proliferation were
      associated significantly with tumor grade. Survival was improved when >or=95% of
      the tumor was resected. Although the total tumor area was associated with overall
      survival, no differences were observed when the amount of necrosis or a tumor
      necrosis index (area of necrosis/area of tumor) was compared with survival. The
      findings indicated that GLUT-1 and VEGF were correlated with survival after
      controlling for age. CONCLUSIONS: Tumor grade was differentiated with HRMs, MVD,
      and proliferation, but only GLUT-1 predicted survival in this group of patients
      with GBM. The results suggested that GLUT-1 may be an important independent
      prognostic indicator.

PMID- 18618498
TI  - Heparanase is overexpressed in lung cancer and correlates inversely with patient
      survival.
AB  - BACKGROUND: Heparanase is an endo-beta-D-glucuronidase that is capable of
      cleaving heparan sulfate (HS) side chains at a limited number of sites, yielding
      HS fragments of still appreciable size (approximately 5-7 kDa). Heparanase
      activity has been detected frequently in several cell types and tissues.
      Heparanase activity correlates with the metastatic potential of tumor-derived
      cells, a correlation that has been attributed to enhanced cell dissemination as a
      consequence of HS cleavage and remodeling of the extracellular matrix barrier.
      METHODS: In this study, the authors examined heparanase expression in 114
      patients with lung cancer by means of immunohistochemistry and correlated
      clinical-pathologic data with heparanase immunostaining and cellular
      localization. RESULTS: Heparanase was overexpressed in 75% of the study patients.
      Heparanase expression was correlated with lung cancer lymph node status and
      metastasis classification (P = .04 and P = .01, respectively) and was correlated
      inversely with patient survival (P = .007). It is noteworthy that this adverse
      effect depended largely on the cellular localization of heparanase. Thus, whereas
      cytoplasmic staining of heparanase is associated with a poor prognosis, nuclear
      heparanase predicts a favorable outcome for patients with lung cancer.
      CONCLUSIONS: The current findings suggest that heparanase expression and cellular
      localization are decisive for lung cancer patients' prognosis, most likely
      because of heparanase-mediated tumor cell dissemination by blood and lymph
      vessels.

PMID- 18618500
TI  - Patterns of care for women with cervical cancer in the United States.
AB  - BACKGROUND: Recommendations for pretreatment evaluation and treatment of cervical
      cancer have significantly evolved over the last decade because of the results of
      multiple randomized studies comparing the addition of platin-based chemoradiation
      as well as the widespread dissemination and use of imaging modalities. This
      analysis was initiated to determine any systemic changes in management of
      cervical cancers. METHODS: Surveillance, Epidemiology, and End Results program
      data were used to sample newly diagnosed women in 1997, 2000, and 2001 with
      cancer of the cervix. A total of 3116 women with no previous diagnosis of cancer
      were selected. Data were reabstracted, additional information not routinely
      collected was obtained, therapy was verified with the treating physician, and
      multiple endpoints were analyzed. RESULTS: A marked rise was observed in the
      percentage receiving chemotherapy (34% to 85%) as well as concurrent
      chemoradiation (20% to 72%) from 1997 to 2001. CONCLUSIONS: The significant
      change in the management and treatment of cervical cancer appears to correspond
      temporally with the publication of 5 clinical trials, all of which showed a
      significant improvement in overall survival associated with chemoradiation. This
      change also corresponded with the NCI Clinical Announcement that was disseminated
      in 1999 to those oncologists most likely to treat women with cervical cancer.

PMID- 18618499
TI  - Differential cytotoxicity of novel somatostatin and dopamine chimeric compounds
      on bronchopulmonary and small intestinal neuroendocrine tumor cell lines.
AB  - BACKGROUND: Survival rates for gastrointestinal (GI) and bronchopulmonary (BP)
      neuroendocrine tumors (NETs) have not significantly altered (overall 67%, 5-year
      survival) in 30 years (1973-2004), whereas the incidence has increased (
      approximately 1000%) in the same time frame. No effective or specific
      antineoplastic agent is available for treatment, although somatostatin analogs
      inhibit tumor secretion. Given the coexistence of somatostatin and dopamine
      regulatory receptors on NET cells, the antiproliferative efficacy as well as the
      signaling and transcriptional targets of their ligands were evaluated. METHODS:
      The cytotoxic effects of 12 somatostatin/dopamine compounds were evaluated in 3
      NET cell lines, and real-time polymerase chain reaction and enzyme-linked
      immunoadsorbent assay studies were performed to delineate antiproliferative
      signaling pathways. RESULTS: The atypical BP-NET, NCI-H720, was most sensitive to
      the sst(5) analog BIM23206 (half-maximal concentration, 2.4 pM) and demonstrated
      similar sensitivity to lanreotide and the sst(2) analog BIM23120. The typical BP
      NET, NCI-H727, was most sensitive to BIM23120 (0.7 nM) and to the pan
      somatostatin receptor analog (BIM23A779). The GI-NET, KRJ-I, was most sensitive
      to sst(2,5) analogs lanreotide (1 nM) and BIM23244 (7.4 nM). Lanreotide activated
      extracellular signal regulated kinase-1/2 phosphorylation and p21(WAF1/CIP1)
      transcription, but inhibited Ki-67 transcription. NCI-H720 was most sensitive to
      the sst(2,5)- and D(2)-selective compound BIM23A761 (4.2 nM), as was NCI-H727
      (5.5 nM). KRJ-I did not respond to any chimeric analog. BIM23A761 activated c-Jun
      N-terminal kinase signaling and caused inhibition of Ki-67 transcription.
      P21(WAF1/CIP1) transcription was activated only in NCI-H727 cells. CONCLUSIONS:
      The different responses of each individual cell line suggested that NETs from
      different locations arising from different neuroendocrine cells may require cell
      specific antiproliferative agents based on the unique receptor profile of
      individual lesions.

PMID- 18618502
TI  - OPRISK: a structured checklist assessing security needs for mentally disordered
      offenders referred to high security psychiatric hospital.
AB  - BACKGROUND: More mentally disordered offenders (MDOs) are referred to secure
      psychiatric care settings than are accepted for admission. Psychiatrists working
      in different care settings may disagree on the appropriate level of security for
      MDOs, resulting in treatment delay. A pre-admission structured assessment of
      security needs for MDOs may facilitate agreement and access to care. AIMS: To
      assess the predictive validity and reliability of a structured assessment of
      security need (OPRISK) in a prospective cohort of referrals to high security
      hospital. METHOD: Operationalized criteria describing risk factors related to
      security need were used to develop OPRISK, an 18 item checklist. The predictive
      validity of OPRISK was assessed prospectively on the outcome of 140 referrals to
      Broadmoor high security hospital. RESULTS: Receiver operating characteristic
      curves of the predictive validity of OPRISK yielded an area under the curve of
      0.765 (p < 0.001, 95% CI: 0.686-0.844). Internal consistency (>0.75) and inter
      rater reliability (0.925) were high. CONCLUSION: OPRISK makes the evidence for an
      MDO's security needs explicit, aiding communication across service settings and
      improving access to care.

PMID- 18618501
TI  - Combination of dexamethasone, high-dose cytarabine, and carboplatin is effective
      for advanced large-cell non-Hodgkin lymphoma of childhood.
AB  - BACKGROUND: The purpose of the current study was to evaluate the activity and
      toxicity of dexamethasone, high-dose cytarabine, and carboplatin (DAC)
      combination therapy in children with newly diagnosed large-cell non-Hodgkin
      lymphoma (NHL) and to estimate the event-free and overall survival rates achieved
      when DAC is incorporated into a conventional regimen. METHODS: From 1991 to 1997,
      20 boys and 5 girls aged 4.2 to 17.7 years who had stage III (according to the
      St. Jude staging system) (n = 21) or stage IV (n = 4) large-cell NHL were treated
      in this study. DAC therapy was administered at the beginning of the induction
      phase in 2 sequential cycles and incorporated throughout a continuation phase
      (modified from the ACOP+ regimen, which features doxorubicin, cyclophosphamide,
      vincristine, and prednisone) with doxorubicin, cyclophosphamide, vincristine, and
      dexamethasone. The total duration of treatment was approximately 10 months.
      RESULTS: DAC therapy yielded a response in 22 of 25 patients (88%; 95% confidence
      interval [95% CI], 68%-97%): complete remission in 13 cases (52%), and partial
      response in 9 (36%). After additional treatment with doxorubicin,
      cyclophosphamide, vincristine, and dexamethasone, complete remission was attained
      in 18 patients (72%) and partial remission in 3 (12%). The event-free survival
      rate (+/- the standard error [SE]) was 64% +/- 9% and the overall survival rate
      was 80% +/- 8% at 5 years. CONCLUSIONS: The results of the current study indicate
      that the DAC regimen is well tolerated and effective for pediatric patients with
      large-cell NHL.

PMID- 18618503
TI  - Characterization of childhood precursor T-lymphoblastic lymphoma by
      immunophenotyping and fluorescent in situ hybridization: a report from the
      Children's Oncology Group.
AB  - BACKGROUND: T-lymphoblastic lymphoma (T-LBL) accounts for 25-30% of childhood non
      Hodgkin's lymphoma and is closely related to T-lymphoblastic leukemia (T-ALL).
      Recently, we demonstrated distinct differences in gene expression between
      childhood T-LBL and T-ALL, but molecular pathogenesis and relevant protein
      expression patterns in T-LBL remain poorly understood. PROCEDURE: Children with T
      LBL with disseminated disease were registered and treated on COG protocol 5971.
      Paraffin-embedded tumor tissue was obtained at diagnosis for immunohistochemistry
      (IHC) and fluorescence in situ hybridization (FISH) studies. We determined the
      pattern and intensity of staining for c-Myc, Skp2, Mib-1, p53, TCL-1, bcl-2, and
      bcl-6 proteins by IHC and c-Myc, p53, bcl-2, bcl-6, and TCR alpha/delta molecular
      alterations by FISH in 22 pediatric T-LBL cases. RESULTS: The majority of T-LBL
      samples expressed Mib-1 (59%) and c-Myc (77%) proteins in greater than 50% of the
      cells, but Skp2 (14%), p53 (14%), and bcl-2 (23%) expression was less common.
      FISH studies demonstrated 18% gains and 10% losses in c-Myc, 16% gains in p53,
      12% gains and 6% losses in bcl-2, and 6% gains and 19% losses in bcl-6 with
      little direct correlation between the IHC and FISH studies. CONCLUSIONS:
      Childhood T-LBL is a highly proliferative tumor associated with enhanced
      expression of c-Myc protein, but without detectable c-Myc molecular alterations.
      FISH studies did not identify consistent etiologies of molecular dysregulation,
      and future studies with other molecular approaches may be required to elucidate
      the molecular pathogenesis of childhood T-LBL.

PMID- 18618504
TI  - Contribution of DNA ploidy image cytometry to the management of ASC cervical
      lesions.
AB  - BACKGROUND: The Bethesda system classifies smears that suggest an underlying
      cervical intraepithelial neoplasia (CIN) as ASC (atypical squamous cell) smears.
      ASC smears are subdivided into ASCUS (of undetermined significance) and ASCH
      (cannot exclude a high-grade lesion). Today the management of ASCUS is a triage
      with HR-HPV testing and colposcopy is recommended for ASCH. The aim was to
      conduct a study on ASC smears to determine DNA ploidy measurement for the
      detection of CIN2+. METHODS: The link between a suspect DNA ploidy assessed by
      image cytometry and/or a positive HR-HPV testing was analyzed on 69 ASCUS and 82
      ASCH smears, and the presence of CIN2+ within 12 months after ASC diagnosis. The
      ploidy was suspect in case of aneuploidy, multiploidy, or in the presence of
      cells with a DNA content >5c or >9c. RESULTS: Every woman who had a CIN2+ had a
      suspect DNA profile in the ASCUS smears and every woman except 1 was HR-HPV
      positive. The link between a positive HR-HPV test or a suspect DNA profile or
      both and a CIN2+ was high (P = .019, .023, and .008, respectively). The presence
      of >9c cells was particularly linked to CIN2+ (P = .0031). In all, 90.9% and
      87.9% of the ASCH smears with CIN2+ were, respectively, HR-HPV positive or had a
      suspect ploidy (P = .0000 and P = .0043), and the presence of >9c cells was also
      linked to CIN2+ (P = .003). CONCLUSIONS: HR-HPV testing and determination of the
      ploidy profile with special attention to 9c-exceeding cells could be accurate for
      a better management of ASC smears.

PMID- 18618505
TI  - Endoscopic ultrasound-guided fine-needle aspiration cytology of pancreatic
      neuroendocrine tumors: a study of 48 cases.
AB  - BACKGROUND: Neuroendocrine tumors (NETs) of the pancreas are relatively uncommon
      tumors. The objective of this report was to describe the cytopathologic and
      immunocytochemical features of NETs obtained by endoscopic ultrasound (EUS)
      guided fine-needle aspiration (FNA). METHODS: Forty-eight patients who were
      diagnosed with pancreatic NETs based on EUS-guided FNA were studied
      retrospectively (from 2002 to 2007). Clinical data, EUS findings, cytopathologic
      features, and immunocytochemical stains were reviewed for this study. The final
      histopathologic diagnosis from each patient also was available for comparison.
      RESULTS: Forty-eight patients (28 men and 20 women) who ranged in age from 16
      years to 86 years were selected and had the following clinical findings: solid or
      multiple pancreatic masses diagnosed by computed tomography or magnetic resonance
      imaging studies; simultaneous, suspicious, metastatic masses in the liver,
      mediastinum, and/or lung; hypoglycemia; multiple endocrine neoplasia type 1
      syndrome; von Hippel-Lindau syndrome; and primary NET of the small bowel. EUS
      findings revealed solid or multiple masses in the pancreatic head/uncinate, or in
      the pancreatic body/tail, or simultaneously in the pancreatic head/uncinate and
      body/tail. Cytologically, 40 patients were diagnosed with NETs (histopathogically
      confirmed), and 8 patients had findings that were suspicious of NETs (2 patients
      had false-positive results, and 6 patients had histopathologically confirmed
      NETs). The most helpful cytologic findings for the diagnosis of NET were a richly
      cellular sample with a monotonous, poorly cohesive population of small or medium
      sized cells with granular chromatin (salt and pepper) and plasmacytoid
      morphology. Immunocytochemistry confirmed the neuroendocrine origin of tumors in
      40 patients (material for immunocytochemistry was inadequate in 8 patients).
      CONCLUSIONS: The current results indicated that EUS-guided FNA is a useful method
      for the diagnosis of pancreatic NETs. Cytopathologic examination in coordination
      with immunocytochemistry can provide an accurate diagnosis in most patients.

PMID- 18618506
TI  - Significant antitumor activity of oncolytic adenovirus expressing human
      interferon-beta for hepatocellular carcinoma.
AB  - BACKGROUND: Human interferon-beta (IFN-beta) has been widely used in gene therapy
      for its antitumor activity but its therapeutic effect is limited. The
      conditionally replicative adenovirus ONYX-015 (a E1B-55-kDa-deleted adenovirus)
      targets well to tumor cells, but is not potent enough to cause significant tumor
      regression. To solve these problems, a tumor-selective replicating adenovirus
      expressing IFN-beta was constructed in this study. METHODS: The oncolytic
      adenoviruses were generated by homologous recombination in packaging cells. The
      expression of the IFN-beta protein was detected by enzyme-linked immunosorbent
      assay (ELISA). The antitumor efficacy of ZD55-IFN-beta was evaluated in cell
      lines and human hepatocellular carcinoma xenografts in nude mice. RESULTS: ZD55
      IFN-beta can express much more IFN-beta than Ad-IFN-beta because of the
      replication of the ZD55 vector. Our data showed that ZD55-IFN-beta could exert a
      strong cytopathic effect on tumor cells (about 100-fold higher than Ad-IFN-beta
      or ONYX-015). Moreover, no obvious cytotoxic or apoptotic effects were detected
      in normal cells infected with ZD55-IFN-beta. CONCLUSIONS: The antitumor efficacy
      of IFN-beta could be significantly improved due to the increased gene expression
      level from the tumor-selective replicating vector. The oncolytic adenovirus
      expressing IFN-beta may provide a novel approach for cancer gene therapy.

PMID- 18618507
TI  - A comparison of survival and disease-specific survival in surgically resected,
      lymph node-positive bronchioloalveolar carcinoma versus nonsmall cell lung
      cancer: implications for adjuvant therapy.

PMID- 18618509
TI  - Primary central nervous system lymphoma: the role of consolidation treatment
      after a complete response to high-dose methotrexate-based chemotherapy.
AB  - BACKGROUND: The most effective treatment for a new diagnosis of primary central
      nervous system lymphoma is high-dose methotrexate (MTX)-based chemotherapy
      followed by whole-brain radiation therapy (WBRT). However, this combined modality
      treatment carries an increased risk of delayed neurotoxicity. For patients who
      achieve a complete response (CR) after induction that uses high-dose MTX-based
      chemotherapy, it is not clear if consolidation treatment is necessary. Therefore,
      a retrospective study was conducted to assess the impact of consolidation
      treatment after a CR to initial induction chemotherapy on disease control and
      survival. METHODS: The authors retrospectively analyzed 122 patients who achieved
      a CR after initial MTX-based chemotherapy. The benefit of consolidation WBRT,
      high-dose cytarabine (HDAC), or both on failure-free (FFS) and overall survival
      (OS) was assessed. RESULTS: With a median follow-up of 60 months, FFS was longer
      in patients who received WBRT plus HDAC as consolidation treatment (P = .03 by
      univariate analysis); there was no difference in OS observed among patients who
      received no consolidation treatment, HDAC alone, WBRT plus HDAC, or WBRT alone.
      Age and Karnofsky performance scale (KPS) were the only independent prognostic
      factors. Patients who received WBRT alone or in combination with HDAC had higher
      rates of neurotoxicity. CONCLUSIONS: Consolidation treatment with WBRT, HDAC, or
      both does not appear to improve survival in patients who achieved a CR with
      induction MTX-based therapy. Age, KPS, and risk of delayed neurotoxicity must be
      considered in the choice of consolidation regimens.

PMID- 18618510
TI  - Never-smoking nonsmall cell lung cancer as a separate entity: clinicopathologic
      features and survival.
AB  - BACKGROUND: To propose 'never-smoking nonsmall cell lung cancer (NSCLC)' as a
      separate entity, the clinicopathologic differences of operable NSCLC between
      never-smoking patients and patients with a history of smoking were investigated.
      METHODS: The medical records of 1405 patients with primary NSCLC who underwent a
      complete resection at the study institution from 1974 through 2004 were reviewed
      for clinicopathologic variables and postoperative survival. RESULTS: The
      proportion of never-smoking patients with NSCLC has been significantly increasing
      over 30 years, from 15.9% in the 1970s to 32.8% in the 2000s. A significantly
      greater proportion of female patients or adenocarcinoma patients was found in the
      'never-smoking NSCLC' group in comparison to the 'smoking NSCLC' group (85.8% vs
      11.2% and 87.8% vs 49.1%, respectively). The proportion of pathologic stage IA
      disease for the 'never-smoking NSCLC' group was significantly higher than that
      for the 'smoking NSCLC' group (40.1% vs 25.4%; P < .0001). With regard to both
      overall and cancer-specific survival, the 'never-smoking NSCLC' patient group was
      significantly superior to the 'smoking NSCLC' group. In addition to smoking
      status, the factors found to be significantly associated with the postoperative
      survival rate were sex, histologic type, T classification, and N classification
      by univariate analyses. A multivariate analysis revealed never-smoking status to
      be an independent prognostic factor in addition to pathologic T and N
      classification. CONCLUSIONS: The differences in the clinicopathologic factors and
      survivals between the 'never-smoking NSCLC' patient group and the 'smoking NSCLC'
      group suggest that NSCLC in never-smokers should be considered a separate disease
      entity.

PMID- 18618511
TI  - Proposal for a new risk model in myelodysplastic syndrome that accounts for
      events not considered in the original International Prognostic Scoring System.
AB  - BACKGROUND: Recent studies have highlighted issues with the International
      Prognostic Scoring System (IPSS) model in relation to the exclusion of many
      subgroups that now represent a large proportion of patients with myelodysplastic
      syndrome (MDS) (eg, secondary MDS, chronic myelomonocytic leukemia [CMML] with
      leukocytosis, prior therapy) and its lack of applicability to most patients on
      investigational programs, because many would have received prior therapies and
      would have had MDS for a significant length of time. METHODS: The authors
      analyzed 1915 patients with MDS who were referred from 1993 to 2005 (including
      those with CMML, secondary MDS, and MDS with prior therapy). Only 507 patients
      (26%) had primary MDS without prior therapy (ie, classifiable by the IPSS).
      Patients were divided randomly into a study group (n = 958) and a test group (n =
      957). RESULTS.: A multivariate analysis of prognostic factors in the study group
      identified the following adverse, independent factors as continuous and categoric
      values (P<.001): poor performance, older age, thrombocytopenia, anemia, increased
      bone marrow blasts, leukocytosis, chromosome 7 or complex (>or=3) abnormalities,
      and prior transfusions. Cutoffs for anemia, thrombocytopenia and blasts, and
      cytogenetic subsets were different according to the IPSS. The new MDS prognostic
      model divided patients into 4 prognostic groups with significantly different
      outcomes. The model was validated in the test group. Applying the prognostic
      score of the new model within the 4 IPSS risk groups, overall, and in patients
      who had primary MDS without prior therapy was found to be highly prognostic in
      each subset. Applying the IPSS within each of the 4 risk groups of the new MDS
      model was not found to be prognostic. CONCLUSIONS: The new model accounts for
      duration of MDS and prior therapy. It is applicable to any patient with MDS at
      any time during the course of MDS.

PMID- 18618512
TI  - Structural properties of bombesin-like peptides revealed by surface-enhanced
      Raman scattering on roughened silver electrodes.
AB  - This work presents a Fourier-transform absorption infrared, Fourier-transform
      Raman, and surface-enhanced Raman scattering (SERS) study of the following
      peptides belonging to the bombesin-like family: phyllolitorin,
      [Leu(8)]phyllolitorin, NMB, NMC, and PG-L. The SERS study was undertaken to
      understand the adsorption mechanism of bombesin-like peptides on an
      electrochemically roughened silver electrode surface and to show changes in the
      adsorption mechanism with alterations in amino acids and small tertiary
      structures. The SERS spectra presented here shows bands mainly associated with
      the Trp(8) residue vibrations. The presence of mainly pyrrole coring vibrations
      for phyllolitorin and [Leu(8)]phyllolitorin and mainly benzene coring modes for
      NMB and NMC indicated that these groups interact with the roughened silver
      electrode surface. Furthermore, N(1)-C(8) and C(3)-C(9) bonds of the PG-L indole
      ring seemed to have nearly a vertical orientation on the electrode surface. In
      addition, distinct vibrations of the C-S fragment were observed in the SERS
      spectra of [Leu(8)]phyllolitorin and PG-L. The strong enhancement of the nu(C=O)
      vibration in the [Leu(8)]phyllolitorin SERS spectrum yielded evidence that the
      intact C=O bond(s) bind strongly to the silver electrode surface, whereas NMC,
      phyllolitorin, and NMB were located near the silver surface. This finding was
      supported by the presence of the nu(C-C(=O)) mode. The amide I band observed at
      1642 and 1634 cm(-1) for NMB and NMC, respectively, and the Raman amide III band
      seen in the 1282-1249 cm(-1) range for all peptides except PG-L, indicate that
      the strongly hydrogen-bonded alpha-helical conformation and random-coil structure
      are favored for binding to the surface.

PMID- 18618513
TI  - Randomized trial of a decision aid for individuals considering genetic testing
      for hereditary nonpolyposis colorectal cancer risk.
AB  - BACKGROUND: Despite the potential benefits of genetic testing for hereditary
      nonpolyposis colorectal cancer (HNPCC) risk, individuals can find the genetic
      testing decision-making process complicated and challenging. The goal of the
      current study was to measure the effectiveness of a tailored decision aid
      designed specifically to assist individuals to make informed decisions regarding
      genetic testing for HNPCC risk. METHODS: In all, 153 individuals were randomized
      to receive the decision aid or a control pamphlet at the end of their first
      genetic counseling consultation. Of these, 109 (71.2%) completed the first
      questionnaire 1 week after consultation, whereas 95 (62.1%) completed the 6-month
      follow-up questionnaire. RESULTS: Although the decision aid had no significant
      effect on postdecisional regret or actual genetic testing decision, the trial
      results demonstrated that participants who received the decision aid had
      significantly lower levels of decisional conflict (ie, uncertainty) regarding
      genetic testing (chi-square(1) = 8.97; P = .003) and were more likely to be
      classified as having made an informed choice concerning genetic testing (chi
      square(1) = 4.37; P = .037) than participants who received a control pamphlet.
      Also, men who received the decision aid had significantly higher knowledge levels
      regarding genetic testing compared with men who received the control pamphlet,
      whereas no such differences were found for women (chi-square(2) = 6.76; P =
      .034). CONCLUSIONS: A decision aid for individuals considering genetic testing
      for HNPCC is an effective intervention to reduce uncertainty and assist
      individuals to make an informed choice regarding genetic testing for HNPCC after
      genetic counseling.

PMID- 18618514
TI  - Genetic stratification of Wilms tumor: is WT1 gene analysis ready for prime time?

PMID- 18618515
TI  - Growth rates of metastatic brain tumors in nonsmall cell lung cancer.
AB  - BACKGROUND: The purpose of the study was to evaluate the growth kinetics of
      metastatic brain tumors during chemotherapy and to analyze growth rates and
      volumetric doubling time of metastatic brain tumors in patients with nonsmall
      cell lung cancer (NSCLC) with tumor regrowth. METHODS: NSCLC patients with
      minimally symptomatic brain metastases who were not treated previously were
      enrolled. Serial magnetic resonance images (MRI) of 30 metastatic brain tumors in
      19 patients were reviewed. Tumor growth rates and volumetric tumor doubling time
      of tumor regrowth were estimated. All patients were treated with front-line
      chemotherapy until disease progression. RESULTS: The median tumor growth rate was
      12.10 mm(3)/day (interquartile range [IQR], 3.09-36.75). The volume percentage
      increase/day was 1.67 (IQR, 0.69-4.59). The median volumetric tumor doubling time
      was 58.48 days (IQR, 32.33-98.48). CONCLUSIONS: These findings may help optimize
      patient management during follow-up. Study results indicated that brain MRI
      should be obtained at a minimum of 2-month intervals to screen for metastatic
      brain tumors.

PMID- 18618516
TI  - Screening for endometrial cancer?

PMID- 18618517
TI  - Assuring the quality of quality assurance: seeding abnormal slides into the
      negative Papanicolaou smears that will be rapid rescreened.
AB  - BACKGROUND: Rapid rescreening (RR) of negative Papanicolaou smears (PS) is used
      in many countries as a quality-assurance measure. Seeding of abnormal slides has
      been suggested as a way to increase the sensitivity of this procedure. Since
      2004, the authors have carried out RR with seeding before issuing reports. In
      this article, they describe their experience. METHODS: Abnormal seeds were
      sourced from the previous day's high-grade cases, both squamous and glandular.
      Slides were evaluated for the 'degree of difficulty' (which was defined as the
      number of fields required to find (fields-to-find [FTF]) the abnormality),
      relabeled, and redotted to make them indistinguishable from the routine RR work.
      The number of seeds found/missed, the identity of the screener, the type of
      seeded abnormality, the degree of difficulty of the seed, and the mapping
      technique used all were recorded. The cytologists also were surveyed about their
      views on seeding. RESULTS: Overall, 14.8% of 3082 high-grade seeds were missed
      during RR. There was no relation between seeds missed and the mapping technique
      used. However, the difficulty of the seed was relevant to the number missed and
      ranged from 8.3% when the FTF was <5 to 36% when the FTF was >10 (P = .000). The
      difference between intraepithelial seeds and invasive seeds was significant for
      squamous seeds (P = .031) but not for glandular seeds. Glandular seeds also were
      more likely to be missed than squamous seeds (23.1% vs 14.3%; P = .002). Most
      cytologists believed that seeding was a good idea and that seeds increased their
      level of vigilance. CONCLUSIONS: The authors' experience demonstrated that
      routine seeding is practicable for both conventional and liquid-based slides.
      With the advent of the human papillomavirus vaccine, abnormalities will become
      rarer, and seeding will be necessary to maintain the alertness of cytologists.

PMID- 18618518
TI  - Clinical and therapeutic implications of the mutational status of IgVH in
      patients with chronic lymphocytic leukemia.
AB  - The past 2 decades have brought major advances to clinicians' understanding of
      the complexities of chronic lymphocytic leukemia (CLL). Novel biologic and
      genetic markers are providing tools for more accurate prediction of responses,
      disease progression, and survival of patients across different stages of CLL.
      Several multivariate analyses have confirmed unmutated IgVH to be an independent
      adverse prognostic marker in patients with CLL. The presence of unmutated IgVH is
      strongly associated with poor-risk genomic aberrations and overexpression of CD38
      and ZAP-70. Nevertheless, these associations are not absolute. The design of
      future clinical trials are already incorporating novel prognostic markers such as
      IgVH, among others, as part of risk-adapted strategies aimed at improving
      treatment outcomes by tailoring the aggressiveness of the therapy proportional to
      disease risk. Such a strategy could minimize unnecessary chemotoxicity in
      patients with favorable prognosis CLL, while reserving more aggressive therapy,
      including allogeneic hematopoietic cell transplantation, for patients with poor
      risk features.

PMID- 18618520
TI  - Effectiveness of an integrated outpatient care programme compared with present
      day standard care in early rheumatoid arthritis.
AB  - OBJECTIVES: To investigate the effectiveness of an integrated care programme in
      daily practice compared with present-day standard care for ambulatory early
      rheumatoid arthritis patients. METHODS: In this cross-sectional study, group A
      received programmed multidisciplinary outpatient care and group B standard
      rheumatologist-centred care. Demographics, disease duration, initial and actual
      treatment, disease activity (Disease Activity-28 Score), general health (Short
      Form-36 [SF-36]), functionality (Health Assessment Questionnaire [HAQ]), coping
      style (Utrecht's Coping List), illness perception (Dutch-Revised Illness
      Perception Questionnaire) and satisfaction about care were recorded. RESULTS:
      Eight-nine patients were included in group A and 102 in group B. Demographics,
      rheumatoid factor, antibodies against cyclic citrullinated peptides and disease
      duration were comparable. More patients in group A received initial combination
      therapy (35% versus 3%). Actual treatment regimens were comparable. More patients
      were in remission (69% versus 39%) or had low disease activity (80% versus 60%),
      mean HAQ-scores were lower (0.52 versus 0.80), more patients had no functional
      impairment (38% versus 15%) and SF-36 scores were higher in group A. Coping style
      and illness perception were similar, except for illness coherence. Satisfaction
      differed only for aspects typically favouring a care programme. Participation in
      a care programme independently predicted remission and absence of disability in a
      regression model, including gender and initial treatment as other predictors.
      CONCLUSION: Disease activity was better controlled and functionality and general
      health better preserved in patients following an outpatient care programme. This
      was partly due to the easier implementation of an intensive initial treatment
      strategy but apparently also to other aspects of organized pharmacological and
      non-pharmacological care, to be defined in randomized, controlled studies.

PMID- 18618519
TI  - Calcium and calcium sensing receptor modulates the expression of thymidylate
      synthase, NAD(P)H:quinone oxidoreductase 1 and survivin in human colon carcinoma
      cells: promotion of cytotoxic response to mitomycin C and fluorouracil.
AB  - Ca(2+) and the cell-surface calcium sensing receptor (CaSR) constitute a novel
      and robust ligand/receptor system in regulating the proliferation and
      differentiation of colonic epithelial cells. Here we show that activation of CaSR
      by extracellular Ca(2+) (or CaSR agonists) enhanced the sensitivity of human
      colon carcinoma cells to mitomycin C (MMC) and fluorouracil (5-FU). Activation of
      CaSR up-regulated the expression of MMC activating enzyme, NAD(P)H:quinone
      oxidoreductase 1 (NQO-1) and down-regulated the expression of 5-FU target,
      thymidylate synthase (TS) and the anti-apoptotic protein survivin. Cells that
      were resistant to drugs expressed little or no CaSR but abundant amount of
      survivin. Disruption of CaSR expression by shRNA targeting the CaSR abrogated
      these modulating effects of CaSR activation on the expression of NQO1, TS,
      survivin and cytotoxic response to drugs. It is concluded that activation of CaSR
      can enhance colon cancer cell sensitivity to MMC and 5-FU and can modulate the
      expression of molecules involved in the cellular responses to these cytotoxic
      drugs.

PMID- 18618521
TI  - Fermented guava leaf extract inhibits LPS-induced COX-2 and iNOS expression in
      Mouse macrophage cells by inhibition of transcription factor NF-kappaB.
AB  - The goal of this study was to elucidate the antiinflammatory activities of
      Psidium guajava L. (guava) leaf. To improve the functionality of guava leaf, it
      was fermented with Phellinus linteus mycelia, Lactobacillus plantarum and
      Saccharomyces cerevisiae. The ethanol extract from fermented guava leaf inhibited
      lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2)
      (PGE(2)) production. Western blot analysis showed that fermented guava leaf
      extract decreased LPS-induced inducible nitric oxide synthase (iNOS) and the
      cyclooxygenase-2 (COX-2) protein level in RAW 264.7 cells. To investigate the
      mechanism involved, the study examined the effect of fermented guava leaf extract
      on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. Fermented guava leaf
      extract significantly inhibited LPS-induced NF-kappaB transcriptional activity.
      Immunochemical analysis revealed that fermented guava leaf extract suppressed LPS
      induced degradation of I-kappaBalpha. Taken together, the data indicate that
      fermented guava leaf extract is involved in the inhibition of iNOS and COX-2 via
      the down-regulation of NF-kappaB pathway, revealing a partial molecular basis for
      the antiinflammatory properties of fermented guava leaf extract.

PMID- 18618522
TI  - Antihyperalgesic effect of a Cannabis sativa extract in a rat model of
      neuropathic pain: mechanisms involved.
AB  - This study aimed to give a rationale for the employment of phytocannabinoid
      formulations to treat neuropathic pain. It was found that a controlled cannabis
      extract, containing multiple cannabinoids, in a defined ratio, and other non
      cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive
      efficacy than the single cannabinoid given alone, when tested in a rat model of
      neuropathic pain. The results also demonstrated that such an antihyperalgesic
      effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was
      mediated by vanilloid receptors TRPV1. The non-psychoactive compound,
      cannabidiol, is the only component present at a high level in the extract able to
      bind to this receptor: thus cannabidiol was the drug responsible for the
      antinociceptive behaviour observed. In addition, the results showed that after
      chronic oral treatment with cannabis extract the hepatic total content of
      cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein
      activity. It is suggested that the inhibition of hepatic metabolism determined an
      increased bioavailability of cannabidiol resulting in a greater effect. However,
      in the light of the well known antioxidant and antiinflammatory properties of
      terpenes and flavonoids which could significantly contribute to the therapeutic
      effects, it cannot be excluded that the synergism observed might be achieved also
      in the absence of the cytochrome P450 inhibition.

PMID- 18618524
TI  - Pharmacological and therapeutic effects of Berberis vulgaris and its active
      constituent, berberine.
AB  - Barberry (Berberis vulgaris L. family Berberidaceae) is well known in Iran and
      various parts of this plant including its root, bark, leaf and fruit have been
      used as folk medicine. The two decades of research has demonstrated different
      pharmacological and therapeutic effects of B. vulgaris and its isoquinoline
      alkaloids (particularly berberine). Studies carried out on the chemical
      composition of the plant show that the most important constituents of this plant
      are isoquinoline alkaloids such as berberine, berbamine and palmatine. Berberine
      represents one of the most studied among the naturally occurring protoberberine
      alkaloids. In addition to B. vulgaris (barberry), berberine is present in many
      other plants and is used for the treatment of different diseases. This article
      reviews the traditional uses and pharmacological effects of total extract and the
      most active ingredient of B. vulgaris (berberine).

PMID- 18618523
TI  - Mosquito larvicidal activity of isolated compounds from the rhizome of Zingiber
      officinale.
AB  - The larvicidal activity of a petroleum ether extract of Zingiber officinale
      Roscoe (Zingiberaceae) was evaluated against Aedes aegypti L. and Culex
      quinquefasciatus Say (Diptera). Bioassay-guided fractionation led to the
      isolation of 4-gingerol (1), (6)-dehydrogingerdione (2) and (6)
      dihydrogingerdione (3); the latter has not previously been reported from Z.
      officinale. The structures were established from infrared (IR), ultraviolet (UV),
      (1)H-nuclear magnetic resonance (NMR), (13)C-NMR and mass spectral data.
      Following a 24 h exposure, compounds 1-3 exhibited larvicidal activities against
      fourth instar larvae of A. aegypti (LC(50) 4.25, 9.80, 18.20 ppm) and C.
      quinquefasciatus (LC50 5.52, 7.66, 27.24 ppm), respectively. The results show
      that the most effective compound was 4-gingerol.

PMID- 18618525
TI  - Chemical constituents and antimicrobial activity of medicinal plants from Ghana:
      Cassia sieberiana, Haematostaphis barteri, Mitragyna inermis and Pseudocedrela
      kotschyi.
AB  - The antimicrobial activity of the sequential n-hexane, acetone and 50% aqueous
      methanol extracts of leaves, stem bark and roots of four species of medicinal
      plants, Cassia sieberiana DC. (Leguminosae), Haematostaphis barteri Hook. f.
      (Anacardiaceae), Mitragyna inermis (Willd.) O. Kuntze (Rubiaceae) and
      Pseudocedrela kotschyi (Schweinf.) Harms (Meliaceae), from Ghana were tested
      against Bacillus subtilis, Pseudomonas syringae and Cladosporium herbarum using
      TLC direct-autobiographic methods. Extracts from leaves, stem bark and roots of
      the four species gave a positive result against at least one test organism.
      Twelve of the 36 extracts were active against B. subtilis, four extracts were
      active against P. syringae and six were active against C. herbarum. Preliminary
      chemical analysis revealed the presence of flavonoids, stilbenes and alkaloids.
      This is the first report of a stilbene from the Anacardiaceae.

PMID- 18618526
TI  - Flying a kite--observations on dual (and triple) diagnosis.

PMID- 18618527
TI  - Justifying risk decisions.

PMID- 18618528
TI  - Filicide: a comparative study of maternal versus paternal child homicide.
AB  - BACKGROUND: Filicide is the murder of a child by a parent. Historically, filicide
      was regarded as a female crime, but nowadays, in the West, men have become
      increasingly likely to be convicted of killing their child. Previous research on
      filicide has primarily focussed on either maternal or paternal filicide rather
      than comparing the two. AIM: The aim of our study is to examine and compare the
      socio-demographic, environmental and psychopathological factors underlying
      maternal and paternal filicide. METHODS: Data were extracted from records in a
      forensic psychiatric observation hospital in Utrecht, in the Netherlands for the
      period 1953-2004. RESULTS: Seventy-nine men and 82 women were detained in the
      hospital under criminal charges in that period, having killed (132) or attempted
      to kill (29) their own child(ren). Differences between men and women were found
      with regard to age, methods of killing and motivation underlying the filicide.
      Conclusions The categories of filicide identified corresponded to those in
      studies from other countries, indicating that filicide follows similar patterns
      throughout the Western world. The fact that 25% of fathers had killed in reaction
      to threatened separation or divorce, and that over a third of men and more than
      half of the women were mentally ill at the time may suggest that increased
      monitoring by primary care physicians under such circumstances might have
      preventive value.

PMID- 18618529
TI  - An evaluation of behavioural and personality differences between native and non
      native male adolescents in the Netherlands ordered into treatment in a forensic
      psychiatric outpatient clinic, and their non-violent peers.
AB  - BACKGROUND: In a previous study of the dynamic criminogenic needs of violent
      outpatients we did not differentiate between native and non-native adolescents,
      but differences between personality traits and problem behaviours may require
      adaptations to any treatment programme. AIM: To compare, in the Netherlands,
      native and non-native adolescents with and without a violence history on
      personality traits and problem behaviours. METHODS: Forty-eight native and 71 non
      native violent male adolescents were recruited from consecutive referrals to a
      forensic outpatient clinic after a violent offence and compared with randomly
      selected male youths in secondary vocational schools, but without a violent
      history, 82 of whom were from Dutch and 79 from non-Dutch descent. Each took part
      in an individual interview to complete a range of personality and behavioural
      rating scales. RESULTS: Native and non-native adolescent outpatients did not
      differ from each other on any measure. Overall, the outpatients scored higher
      than the students on hostility but not aggressive behaviour, but there were
      differences within the student group according to descent, with the native
      students having higher agreeableness scores and lower hostility and aggressive
      behaviour scores than the students of non-Dutch descent. CONCLUSION: Our study
      suggested that any differences in behavioural or personality traits seen in the
      general adolescent population according to descent are not reflected in a violent
      offender group of similar age. It therefore seems unlikely to be necessary to run
      different treatment programmes for native and non-native adolescent offenders.

PMID- 18618530
TI  - Behaviour problems in childhood and adolescence in psychotic offenders: an
      exploratory study.
AB  - BACKGROUND: Several studies have shown that adults who develop schizophrenia and
      commit a criminal offence may already have shown behaviour problems in childhood
      or adolescence. It is less clear whether such problems follow a particular
      pattern in such patients. AIMS: To examine the utility of the Child Behavior
      Checklist (CBCL) among offenders, to test whether externalizing behaviour
      problems, as measured by the CBCL, are more frequent in psychotic offenders than
      in non-offenders with psychosis, and to investigate relationships between early
      behavioural problems and adult personality disorder in psychotic offenders.
      METHODS: Three groups of violent offenders detained under the Dutch Entrustment
      Act (TBS-detainees)(n = 78) and one group of psychotic patients in general
      psychiatry (n = 16) were rated from case records on the CBCL. RESULTS: There was
      a significant difference between psychotic offenders with a personality disorder
      (n = 25) and the non-offender patients with psychosis (n = 16) on the 'delinquent
      behavior' scale, but no such difference between psychotic offenders with (n = 25)
      and without (n = 21) personality disorder. A hierarchic cluster analysis revealed
      significantly higher scores for externalizing behaviour in all TBS-detainees with
      a personality disorder. Those starting to offend early had higher scores for
      externalizing behaviour than late starters. CONCLUSIONS: Psychotic and non
      psychotic offenders with personality disorder resemble one another in their early
      childhood behaviour problems; psychotic offenders without a personality disorder
      differ from these two groups but resemble non-offenders with psychosis. In
      contrast to findings in non-forensic populations, there were no differences on
      other problem scales of the CBCL. Given the small sample sizes, replication is
      needed, but the findings lend weight to treatment models which focus on the
      psychosis in the latter two groups but extend also to personality disorder in the
      former.

PMID- 18618531
TI  - Synthesis of 2-arylbenzoxazoles by copper-catalyzed intramolecular oxidative C-O
      coupling of benzanilides.

PMID- 18618532
TI  - Rotational probes of six conformers of neutral cysteine.

PMID- 18618533
TI  - Why are selenouracils as basic as but stronger acids than uracil in the gas
      phase?
AB  - The gas-phase basicity and acidity of 2-selenouracil (2SU), 4-selenouracil (4SU),
      and 2,4-diselenouracil (24SU) have been calculated at the B3LYP/6-311+G(3df,2p)
      level of theory. Our results showed that all these compounds behave as bases of
      moderate strength in the gas phase. As was found for uracil and for the
      thiouracil analogues, the most basic site is the heteroatom at position 4, and
      only for 2SU is there a certain ambiguity in assigning the basic site. More
      importantly, with the only exception of 2SU, selenouracils are as basic as or
      slightly less basic than uracil, because the replacement of the oxygen atom at
      position 2 by a selenium atom leads to an increase of the electron delocalization
      inside the six-membered ring, which decreases the intrinsic basicity of the
      heteroatom at position 4. As already reported for uracil and thiouracils, for
      selenouracils N1 is the most acidic site. However, selenouracils are predicted to
      be stronger acids than uracil. This acidity enhancement is essentially due to a
      specific stabilization of the anion when O is replaced by Se. Two factors are
      responsible for this stabilization: a significant aromatization of the ring upon
      deprotonation and a better dispersion of the excess electron density when the
      system contains third-row atoms.

PMID- 18618534
TI  - From biological towards artificial molecular motors.
AB  - Novel single-molecule techniques allow the observation of single-molecular motors
      in real time under physiological conditions. This enables one to gain previously
      inaccessible information about the mechanics of molecular motors, especially
      their mechano-chemical coupling. As an example, we discuss the DNA import motor
      of the bacteriophage phi29 and protein import into chloroplasts. In contrast to
      these highly developed biological molecular motors, artificial molecular motors
      are still at an early stage of development. Nevertheless, they already give a
      wealth of information. Our review focuses on how the investigation of artificial
      and biological molecular motors can mutually enrich each other.

PMID- 18618535
TI  - Computational study on the antifreeze glycoproteins as inhibitors of clathrate
      hydrate formation.
AB  - The ability of antifreeze glycoproteins to inhibit clathrate-hydrate formation is
      studied using DFT. A 5(12) cavity, dodecahedral (H(2)O)(20), and the AATA peptide
      are used to model the inhibitor-clathrate interaction. The presence of AATA in
      the vicinity of the water cavities not only leads to the formation of complexes,
      with different peptide/cavity ratios, but also to the deformation of the cavity
      and to the elongation of several of the hydrogen bonds responsible for keeping
      the dodecahedral (H(2)O)(20) together. The complexes are formed through hydrogen
      bonding between the peptides and the water cavities. The glycoproteins are
      expected to anchor onto the clathrate surface, blocking the access of new water
      molecules and preventing the incipient crystals from growing. They are also
      expected to weaken the clathrate structure. Amide IR bands are associated with
      the complexes' formation. They are significantly red-shifted in the hydrogen
      bonded systems compared to isolated AATA. The amide A band is the most sensitive
      to hydrogen bonding. In addition a distinctive band around 3100 cm(-1) is
      proposed for the identification of clathrate-peptide hydrogen-bonded complexes.

PMID- 18618536
TI  - A combined experimental and theoretical study of the molecular inclusion of
      organometallic sandwich complexes in a cavitand receptor.
AB  - We describe herein a detailed study of the inclusion processes of several
      positively charged organometallic sandwich complexes inside the aromatic cavity
      of the self-folding octaamide cavitand 1. In all cases, the binding process
      produces aggregates with a simple 1:1 stoichiometry. The resulting inclusion
      complexes are not only thermodynamically stable, but also kinetically stable on
      the (1)H NMR spectroscopy timescale. The binding constants for the inclusion
      complexes were determined by different titration techniques. We have also
      investigated the kinetics of the binding process and the motion of the
      metallocenes included in the aromatic cavity of the host. Using DFT-based
      calculations, we have evaluated the energies of a diverse range of potential
      binding geometries for the complexes. We then computed the proton chemical shifts
      of the included guest in each one of the binding geometries. The agreement
      between the averaged computed values and the experimentally determined chemical
      shifts clearly supports the proposed binding geometries that we assigned to the
      inclusion complexes formed in solution. The combination of experimental and
      theoretical results has allowed us to elucidate the origins of the distinct
      features detected in the complexation process of the different guests, as well as
      their different motions inside the host.

PMID- 18618537
TI  - Glycomimetics and glycodendrimers as high affinity microbial anti-adhesins.
AB  - Adhesion to epithelial surface is often the first step in bacterial and viral
      infection. In this process, the microbes use a variety of proteins for
      interaction with host carbohydrates presented as glycoconjugates on cell
      surfaces. Crystal structures of adhesin and lectin binding sites in complexes
      with oligosaccharide open the route for design and synthesis of glycomimetics,
      glycodendrimers, and glycopolymers that are able to block infection at an early
      stage.

PMID- 18618538
TI  - A simple and effective catalytic system for epoxidation of aliphatic terminal
      alkenes with manganese(II) as the catalyst.
AB  - A simple catalytic system that uses commercially available manganese(II)
      perchlorate as the catalyst and peracetic acid as the oxidant is found to be very
      effective in the epoxidation of aliphatic terminal alkenes with high product
      selectivity at ambient temperature. Many terminal alkenes are epoxidised
      efficiently on a gram scale in less than an hour to give excellent yields of
      isolated product (>90 %) of epoxides in high purity. Kinetic studies with some C9
      alkenes show that the catalytic system is more efficient in epoxidising terminal
      alkenes than internal alkenes, which is contrary to most commonly known
      epoxidation systems. The reaction rate for epoxidation decreases in the order: 1
      nonene>cis-3-nonene>trans-3-nonene. ESI-MS and EPR spectroscopic studies suggest
      that the active form of the catalyst is a high-valent oligonuclear manganese
      species, which probably functions as the oxygen atom-transfer agent in the
      epoxidation reaction.

PMID- 18618539
TI  - Nematic and columnar ordering of a PEG-peptide conjugate in aqueous solution.
AB  - The self-assembly in aqueous solution of a PEG-peptide conjugate is studied by
      spectroscopy, electron microscopy, rheology and small-angle X-ray and neutron
      scattering (SAXS and SANS). The peptide fragment, FFKLVFF is based on fragment
      KLVFF of the amyloid beta-peptide, Abeta(16-20), extended by two hydrophobic
      phenylalanine units. This is conjugated to PEG which confers water solubility and
      leads to distinct self-assembled structures. Small-angle scattering reveals the
      formation of cylindrical fibrils comprising a peptide core and PEG corona. This
      constrained structure leads to a model parallel beta-sheet self-assembled
      structure with a radial arrangement of beta sheets. On increasing concentration,
      successively nematic and hexagonal columnar phases are formed. The flow-induced
      alignment of both structures was studied in situ by SANS using a Couette cell.
      Shear-induced alignment is responsible for the shear thinning behaviour observed
      by dynamic shear rheometry. Incomplete recovery of moduli after cessation of
      shear is consistent with the observation from SANS of retained orientation in the
      sample.

PMID- 18618541
TI  - High-density algal photobioreactors using light-emitting diodes.
AB  - Lack of high-density algal photobioreactors (PBR) has been a limitation in
      exploiting the biotechnological potential of algae. Recent developments of highly
      efficient light-emitting diodes (LED using gallium aluminum arsenide chips) have
      made the development of a small LED-based PBR possible. We have calculated
      theoretical values of gas mass transfer requirements and light-intensity
      requirement to support high-density algal cultures for the 680 nm monochromatic
      red light from LED as a light source. A prototype PBR has been designed based on
      these calculations. A cell concentration of more than 2 x 10(9) cells/mL (more
      than 6.6% v%sol;v), cell doubling times as low as 12 h, and an oxygen production
      rate as high as 10 mmol oxygen/L culture/h were achieved using on-line
      ultrafiltration to periodically provide fresh medium. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18618542
TI  - On-line estimation of biological variables during pH controlled lactic acid
      fermentations.
AB  - Indirect measurement of lactose, galactose, lactic acid, and biomass
      concentration from on-line sodium hydroxide weight measurements have been
      obtained for pure and mixed batch cultures of Streptococcus salivarius ssp.
      thermophilus 404 and Lactobacillus delbrueckii subsp. bulgaricus 398 conducted at
      controlled pH and temperature. Linear correlations were established between the
      equivalent sodium hydroxide concentration and the lactose (substrate), galactose
      and lactic acid (products) concentrations while nonlinear relationships were
      developed between biomass and lactic acid concentrations. These nonlinear
      relationships took into account the inhibitory effect of lactic acid on growth
      and acidification. The indirect measurements of biomass concentration were
      introduced into a nonlinear estimator of the state variables and of the specific
      growth and lactic acid production rates. Good agreement was found between
      estimated and measured biomass concentrations (error index ranging from 10.8% to
      12.6%). The results showed the feasibility of on-line estimation of biomass
      concentration and of the specific kinetics from NaOH addition weight measurements
      and its applicability for monitoring lactic acid fermentations. Using off-line
      measurements of L(+) and D(-) lactic acid concentrations, the evolution of the
      concentration of each strain in mixed cultures was obtained from the
      relationships proposed for the mixed cultures. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618543
TI  - A fluid dynamic study of the retrofitting of large agitated bioreactors:
      Turbulent flow.
AB  - Studies were conducted in three 19-m(3) fermentors (14 m(3) working volume,
      aspect ratio = 3:1), one fitted with four Rushton turbines (D/T = 0.35), one with
      three Lightnin' A315 hydrofoil impellers (D/T = 0.46). The power drawn under the
      same aerated conditions relative to the unaerated ones was always greater with
      the hydrofoils, which gives them the potential for enhanced mass transfer rates
      under practical operating conditions. However, the power draw was also sensitive
      to the magnitude of the unaerated power. Indeed, at low unaerated specific power
      ( approximately 0.6 W-kg) and high air flow rates ( approximately 1vvm), the
      relative power draw with the hydrofoils could be even greater than 1. The hold-up
      with each of the impellers was broadly similar at the same aeration rate and
      power input, though the later had a much smaller impact in these large vessels
      than has been reported in the literature based on smaller scale work. As usual,
      repressed coalescence caused increased hold-up, and, with the hydrofoils, this
      increase was associated with a lower power draw. Because of the greater
      mechanical vibration of the reactors with the hydrofoils, vibration
      characteristics of the vessels were measured and they were very similar. The
      results showed that provided care is taken in the mechanical design of the
      system, such impellers can operate reliably in large-scale fermentations with the
      potential for enhanced biological performance. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618544
TI  - A dense cell retention culture system using stirred ceramic membrane reactor.
AB  - A novel reactor design incorporating porous ceramic tubes into a stirred jar
      fermentor was developed. The stirred ceramic membrane reactor has two ceramic
      tubular membrane units inside the vessel and maintains high filtration flux by
      alternating use for filtering and recovering from clogging. Each filter unit was
      linked for both extraction of culture broth and gas sparging. High permeability
      was maintained for long periods by applying the periodical control between
      filtering and air sparging during the stirred retention culture of Saccharomyces
      cerevisiae. The ceramic filter aeration system increased the k(L)a to about five
      times that of ordinary gas sparing. Using the automatic feeding and filtering
      system, cell mass concentration reached 207 g/L in a short time, while it was 64
      g/L in a fed-batch culture. More than 99% of the growing cells were retained in
      the fermentor by the filtering culture. Both yield and productivity of cells were
      also increased by controlling the feeding of fresh medium and filtering the
      supernatant of the dense cells culture. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618545
TI  - A facile transphosphatidylation reaction using a culture supernatant of
      actinomycetes directly as a phospholipase D catalyst with a chelating agent.
AB  - An attempt was made to use the phospholipase D (PLD)- containing culture
      supernatants of actinomycetes directly as catalysts for the
      transphosphatidylation reaction of phosphatidylcholine (PC) to
      phosphatidylethanolamine (PE) in a biphasic system. Of the five actinomycetes
      (three Streptomyces sp. and two Streptoverticillium sp.) examined, three (St.
      mediocidicus, Stv. cinnamoneum and Stv. hachijoense) exhibited good PLD
      production performance, but the selectivity (ratio of transphosphatidylation to
      hydrolysis) of the PLDs in the culture supernatant of all three actinomycetes
      were significantly low. However, the addition of EDTA to the reaction mixture as
      a chelating agent remarkably improved the selectivity of the PLDs, which
      approached 100% in all the culture supernatants. Commercially available PLDs were
      also investigated and classified into two types. The PLDs of one type had high
      selectivity and no metal was required for the enzyme activity, while those of the
      other type showed low selectivity and a metal was necessary for the enzyme to be
      activated. From this finding, it was considered that the culture supernatants
      used in this study contained several PLDs of both types. When the chelating agent
      was added to the reaction mixture, the hydrolysis due to PLDs with low
      selectivity was suppressed by removal of the essential metal, resulting in an
      increased in the overall selectivity of the PLDs in the culture supernatant.
      Repeated batch transphosphatidylation reactions were performed 20 times, reusing
      the PLDs in the aqueous phase by centrifugation; the reaction rate gradually
      decreased to 60% of that of batch 1 by batch 20. This suggests that the
      transphosphatidylation reaction using a culture supernatant has potential for
      industrial application. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618546
TI  - Viability and protein secretion from human Hepatoma (HepG2) cells encapsulated in
      400-mum polyacrylate microcapsules by submerged nozzle-liquid jet extrusion.
AB  - An interfacial precipitation process to encapsulate mammalian cells in
      hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) microcapsules of
      approximately 750 in approximately m diameter was previously described. It was
      not possible to produce smaller capsules due to low shearing force. A new droplet
      generation scheme was developed by suspending the cell and polymer co-extrusion
      nozzle in a uniform co-axial fluid jet which enabled the production of 300 to 600
      microm diameter capsules. HepG2 hepatoma cells in 400-microm-diameter HEMA-MMA
      capsules were able to retain their metabolic activity during and after the
      encapsulation process. The in vitro secretion of plasma proteins alpha(1)-acid
      glycoprotein, alpha(1)-antitrypsin, and fibrinogen by the encapsulated cells was
      retained. The encapsulated cells secreted less fibrinogen (340 kD) relative to
      alpha(1)-acid glycoprotein (42kD), indicating the sieving effect (but not
      absolute cut-off) of the HEMA-MMA membrane. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618547
TI  - Rapid screening for metabolite overproduction in fermentor broths, using
      pyrolysis mass spectrometry with multivariate calibration and artificial neural
      networks.
AB  - Binary mixtures of model systems consisting of the antibiotic ampicillin with
      either Escherichia coli or Staphylococcus auresu were subjected to pyrolysis mass
      spectrometry (PyMS). To deconvolute the pyrolysis mass spectra, so as to obtain
      quantitative information on the concentration of ampicilin in the mixtures,
      partial least squares regression (PLS), principal components regression (PCR),
      and fully interconnected feedforward artificial neural networks (ANNs) were
      studied. In the latter case, the weights were modified using the standard
      backpropagation algorithm, and the nodes used a sigmoidal squsahing funciton. It
      was found that each of the methods could be used to provide calibration models
      which gave excellent predictions for the concentrations of ampicillin in samples
      on which they had not been trained. Furthermore, ANNs trained to predict the
      amount of ampicilin in E. coli were able to generalise so as to predict the
      concentration of ampicillin in a S. aureus background, illustrating the
      robustness of ANNs to rather substantial variations in the biological background.
      The PyMS of the complex mixture of ampicilin in bacteria could not be expressed
      simply in terms of additive combinations of the spectra describing the pure
      components of the mixtures and their relative concentrations. Intermolecular
      reactions took place in the pyrolysate, leading to a lack of superposition of the
      spectral components and to a dependence of the normalized mass spectrum on sample
      size. Samples from fermentations of a single organism in a complex production
      medium were also analyzed quantitatively for a drug of commercial interest. The
      drug could also be quantified in a variety of mutant-producing strains cultivated
      in the same medium. The combination of PyMS and ANNs constitutes a novel, rapid,
      and convenient method for exploitation in strain improvement screening programs.
      (c) 1994 John Wiley & Sons, Inc.

PMID- 18618548
TI  - Diffusion of acetophenone and phenethyl alcohol in the calcium-alginate-bakers'
      yeast-hexane system.
AB  - The intrabead diffusion coefficients of acetophenone and phenethyl alcohol were
      measured at 30 degrees C in the triphasic immobilized yeast-water-hexane system.
      Saccharomyces cerevisiae cells were deactivated with hydrochloric acid and
      entrapped in calcium-alginate beads. Measurements of dry cell loss during
      deactivation, shrinkage of the beads during deactivation and the final porosity
      of the beads were made for various cell loadings. Final concentrations of wet
      cells in the beads ranged from approximately 0.25 to 0.30 g/mL. Mass transfer in
      the hexane phase, external to the beads, was eliminated experimentally. The
      estimated error of 5% to 10% in the diffusion coefficients is within the
      experimental error associated with the bead method. The effect of significant
      sampling volumes on the diffusivities was estimated theoretically and accounted
      for experimentally. The intrabead concentration of acetophenone and phenethyl
      alcohol was 150 to 800 ppm. The deactivated cells were shown to be impervious to
      acetophenone so that the measured diffusivities are extracellular parameters. The
      cell volume fraction in the beads ranged from 0.70 to 0.90, significantly higher
      than previously reported data. The effective diffusion coefficients conform to
      the random pore model. No diffusional interaction between acetophenone and
      phenethyl alcohol was observed. The addition of 2 vol% ethanol or methanol
      slightly increased the diffusivities. The thermodynamic partition coefficients
      were measured in the bead-free water-organic system and found to be an order of
      magnitude lower than the values calculated from the analysis of the diffusion
      data for the organic-bead system, suggesting that bead-free equilibrium data
      cannot be used in triphasic systems. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618549
TI  - Broth recycle in a yeast fermentation.
AB  - Fermentation is a water-intensive process requiring treatment of large amounts of
      effluent broth. It is desirable to increase the ratio of product produced to the
      volume of effluent by minimizing the discharge of effluent from the fermentation
      process. A study of recycling spent fermentation process. A study of recycling
      spent fermentation broth for the subsequent fermentation was carried out with
      Apiotrichum curvatum an oleaginous yeast, as the working culture. Spent broth
      from a defined medium was recycled t replace as much as 75% of the water and
      salts for subsequent batches and this was repeated for seven sequential batches
      without affecting cell mass and lipid production. A 64% vlume reduction of
      wastewater was achieved in this manner. However, when using whey permeate as the
      medium, lipid production dropped after three consecutive recycle operations at
      50% recycle, and after two consecutive recycle operations at 75% and 100%
      recycle. Accumulation of ions in the broth appeared to be responsible for the
      inhibition. An ion exchange step was able to eliminate the ion buildup and
      restore fermentation performance. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618550
TI  - Effect of temperature on nucleotide pools and monoclonal antibody production in a
      mouse hybridoma.
AB  - The specific monoclonal antibody productivity (q(Mab)) of a murine hybridoma
      (CC9C10) increased with incubation temperature in the range 33 degrees C to 39
      degrees C. q(Mab) was constant at each temperature and was independent of the
      phase of culture. The q(Mab) increased 97% at 39 degrees C and decreased by 21%
      at 33 degrees C compared with controls at 37 degrees C. Specific rates of
      substrate (glucose and glutamine) utilization and byproduct (lactate and ammonia)
      formation also increased with temperature but the yield coefficient, Y(Lac/Llc')
      was constant for 33 degrees C to 39 degrees C and Y(Amm/Gin) was constant for 37
      degrees C to 39 degrees C. Y(Amm/Gin) at 33 degrees C was lower than the control.
      Changes in specific nucleotide concentrations and ratios were monitored by
      analysis of intracellular nucleotide pools. The NTP ratio, (ATP + GTP)/(UTP +
      CTP), increased and the U-ratio (UTP/UDP-GNac) decreased during the course of
      each culture, whereas the adenylate energy charge, (ATP + 0.5ADP)/(ATP + ADP +
      AMP), remained relatively constant at a value 0.8. The relative content of UDP-/N
      acetyl galactosamine, UDP-N acetyl glucosamine, and NAD increased with incubation
      temperature, whereas the relative ATP content, SA(ATP + ADP + AMP)/SU (UTP + UDP
      sugars) ratio, purine/pyrimidine, ATP/GTP, and U-ratio decreased at higher
      incubation temperatures. It is possible that these nucleotide parameters may have
      a regulatory role in the changes of q(Mab) observed at the higher temperatures.
      (c) 1994 John Wiley & Sons, Inc.

PMID- 18618551
TI  - Bubble bed reactor: A reactor design to minimize the damage of bubble aeration on
      animal cells.
AB  - A new bubble aeration system was designed to minimize cell killing and cellular
      damage due to sparging. The residence time of the bubbles in the developed bubble
      bed reactor was prolonged dramatically by floating them in a countercurrent
      produced by an impeller. The performance of the new reactor bubble aeration
      system, implemented in a laboratory reactor, was tested in dynamic aeration
      experiments with an without cells. An efficiency up to 95% in oxygen transfer
      could be achieved, which enables a much lower gas flow rate compared with
      conventional bubble aeration reactors. The low gas flow rate is important to keep
      cell damage by bubbles as low as possible. A laser light sheet technique used to
      find the optimal flow pattern in the reactor. The specific power dissipation of
      the impeller is a good measure to predict cell damage in a turbulent flow.
      Typical values for the power dissipation measured in the bubble bed reactor were
      in the range of 0.002 to 0.013 W/kg, which is far below the critical limit for
      animal cells. The growth of a hybridoma cell line was studied in cell cultivation
      experiments. A protein-free medium without supplements such as serum or Pluronic
      F68 was used to exclude any effect of cell-protecting factors, No difference in
      the specific growth rate and the yield of the antibodies was observed in cell
      grown in the bubble free surface aeration in the spinner flask. In contrast to
      the spinner flask, however, the bubble bed reactor design could be scaled up. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18618552
TI  - Hydrogen production from organic substrates in an aerobic nitrogen-fixing marine
      unicellular cyanobacterium Synechococcus sp. strain Miami BG 043511.
AB  - Synechococus sp. strain Miami BG 043511 exhibits very high H(2) photoproduction
      from water, but the H(2) photoproduction capability is lost rapidly with the age
      of the batch culture. The decreases of the capability coincides with the decrease
      of cellular glucose (glycogen) content. However, H(2) photoproduction capability
      can be restored by the addition of organic substrates. Among 40 organic compounds
      tested, carbohydrates such as glucose, fructose, maltose, and sucrose were
      effective electron donors. Among organic acids tested, only pyruvate was an
      effective electron donor. Among alcohols tested, glycerol was a good electron
      donor. These results demonstrate that this unicellular cyanobacterium exhibits a
      wide substrate specificity for H(2) photoproduction but has a different substrate
      specificity compared to photosynthetic bacteria. The maximum rates of H(2)
      photoproduction from a 6-day-old batch culture with 25 mmol of pyruvate, glucose,
      maltose, sucrose, fructose, and glycerol were 1.11, 0.62, 0.50, 0.47, 0.30, and
      0.39 micromoles per mg cell dry weight per hour respectively. Therefore, this
      cyanobacterium strain may have a potential significance in removing organic
      materials from the wastewater and simultaneously transforming them to H(2) gas, a
      pollution free energy. The activity of nitrogenase, which catalyzes hydrogen
      production, completely disappeared when intracellular glucose (glycogen) was used
      up, but it could be restored by the addition of organic substrates such as
      glucose and pyruvate. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618553
TI  - Protein separation by differential drainage from foam.
AB  - Commercially available beer, which is a dilute solution containing components of
      yeast, malt, and hop used in the manufacture of the beer, was used as a model
      system to demonstrate the potential of foam fractionation beyond the primary
      foaming stage. Most of the components present in the beer concentrated in the
      initial foam, but they drained differentially in the subsequent collapsed foam
      collected over a period of 30 min. This resulted in further enrichment, in
      particular, of components which were present in low concentration in the original
      beer, Preferential drainage from foam, hence, might provide a novel way of
      fractionating further the proteins concentrated initially in the liquid films of
      foam. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618554
TI  - Effect of support material and enzyme pretreatment on enantioselectivity of
      immobilized subtilisin in organic solvents.
AB  - Subtilisin Carlsberg was covalently attached to five macroporous acrylic supports
      of varying aquaphilicity (a measure of hydrophilicity). Kinetic parameters of the
      transesterification of S and R enantiomers of secphenethyl alcohol with vinyl
      butyrate, catalyzed by various immobilized subtilisins, were determined in
      anhydrous dioxane and acetonitrile. Enzyme enantioselectivity in acetonitrile,
      but not in dioxane, correlated with the aquaphilicity of the support; a
      mechanistic rationale for this phenomenon was proposed. Although the catalytic
      activity of immobilized subtilisin in anhydrous solvents strongly depended on
      enzyme pretreatment, the enantioselectivity was essential conserved. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18618555
TI  - Probing protein-chaperone interactions with single-molecule fluorescence
      spectroscopy.

PMID- 18618556
TI  - A core-corona hierarchical manganese oxide and its formation by an aqueous soft
      chemistry mechanism.

PMID- 18618557
TI  - Critical size for intracluster proton transfer from water to an anion.

PMID- 18618558
TI  - Enantioselective kinetic resolution of trans-cycloalkane-1,2-diols.

PMID- 18618559
TI  - In situ ATRP-mediated hierarchical formation of giant amphiphile bionanoreactors.

PMID- 18618560
TI  - Solution structures of beta peptides from Raman optical activity.

PMID- 18618561
TI  - Tuning the basicity of synergic bimetallic reagents: switching the
      regioselectivity of the direct dimetalation of toluene from 2,5- to 3,5
      positions.

PMID- 18618562
TI  - Coordination chemistry of conformation-flexible 1,2,3,4,5,6
      cyclohexanehexacarboxylate: trapping various conformations in metal-organic
      frameworks.
AB  - To study the conformations of 1,2,3,4,5,6-cyclohexanehexacarboxylic acid (H(6)L),
      eleven new coordination polymers have been isolated from hydrothermal reactions
      of different metal salts with 1e,2a,3e,4a,5e,6a-cyclohexanehexacarboxylic acid
      (3e+3a, H(6)L(I)) and characterized. They are [Cd(12)(mu(6)-L(II))(mu(10)
      L(II))(3)(mu-H(2)O)(6)(H(2)O)(6)]16.5 H(2)O (1), Na(12)[Cd(6)(mu(6)-L(II))(mu(6)
      L(III))(3)]27 H(2)O (2), [Cd(3)(mu(13)-L(II))(mu-H(2)O)] (3), [Cd(3)(mu(6)
      L(III))(2,2'-bpy)(3)(H(2)O)(3)]2 H(2)O (4), [Cd(4)(mu(4)-L(VI))(2)(4,4'
      Hbpy)(4)(4,4'-bpy)(2)(H(2)O)(4)]9.5 H(2)O (5), [Cd(2)(mu(6)-L(II))(4,4'
      Hbpy)(2)(H(2)O)(10)]5 H(2)O (6), [Cd(3)(mu(11)-L(VI))(H(2)O)(3)] (7), [M(3)(mu(9)
      L(II))(H(2)O)(6)] (M=Mn (8), Fe (9), and Ni (10)), and [Ni(4)(OH)(2)(mu(10)
      L(II))(4,4'-bpy)(H(2)O)(4)]6 H(2)O (11). Three new conformations of 1,2,3,4,5,6
      cyclohexanehexacarboxylate, 6e (L(II)), 4e+2a (L(III)) and 5e+1a (L(VI)), have
      been derived from the conformational conversions of L(I) and trapped in these
      complexes by controlling the conditions of the hydrothermal systems. Complexes 1
      and 2 have three-dimensional (3D) coordination frameworks with nanoscale cages
      and are obtained at relatively low temperatures. A quarter of the L(I) ligands
      undergo a conformational transformation into L(II) while the others are
      transformed into L(III) in the presence of NaOH in 2, while all of the L(I) are
      transformed into L(II) in the absence of NaOH in 1. Complex 3 has a 3D condensed
      coordination framework, which was obtained under similar reaction conditions as
      1, but at a higher temperature. The addition of 2,2'-bipyridine (2,2'-bpy) or
      4,4'-bipyridine (4,4'-bpy) to the hydrothermal system as an auxiliary ligand also
      induces the conformational transformation of H(6)L(I). A new L(VI) conformation
      has been trapped in complexes 4-7 under different conditions. Complex 4 has a 3D
      microporous supramolecular network constructed from a 2D L(III)-bridged
      coordination layer structure by pi-pi interactions between the chelating 2,2'-bpy
      ligands. Complexes 5-7 have different frameworks with L(II)/L(VI) conformations,
      which were prepared by using different amounts of 4,4'-bpy under similar
      synthetic conditions. Both 5 and 7 are 3D coordination frameworks involving the
      L(VI) ligands, while 6 has a 3D microporous supramolecular network constructed
      from a 2D L(II)-bridged coordination layer structure by interlayer N(4,4'-Hbpy)-
      HO(L(II)) hydrogen bonds. 3D coordination frameworks 8-11 have been obtained from
      the H(6)L(I) ligand and the paramagnetic metal ions Mn(II), Fe(II), and Ni(II),
      and their magnetic properties have been studied. Of particular interest to us is
      that two copper coordination polymers of the formulae [{Cu(II) (2)(mu(4)
      L(II))(H(2)O)(4)}{Cu(I) (2)(4,4'-bpy)(2)}] (12 alpha) and [Cu(II)(Hbtc)(4,4'
      bpy)(H(2)O)]3 H(2)O (H(3)btc=1,3,5-benzenetricarboxylic acid) (12 beta) resulted
      from the same one-pot hydrothermal reaction of Cu(NO(3))(2), H(6)L(I), 4,4'-bpy,
      and NaOH. The Hbtc(2-) ligand in 12 beta was formed by the in situ
      decarboxylation of H(6)L(I). The observed decarboxylation of the H(6)L(I) ligand
      to H(3)btc may serve as a helpful indicator in studying the conformational
      transformation mechanism between H(6)L(I) and L(II-VI). Trapping various
      conformations in metal-organic structures may be helpful for the stabilization
      and separation of various conformations of the H(6)L ligand.

PMID- 18618564
TI  - Resonance Raman spectra and Raman excitation profiles of rhodamine 6G from time
      dependent density functional theory.

PMID- 18618563
TI  - Conjugation of spermine facilitates cellular uptake and enhances antitumor and
      antibiotic properties of highly lipophilic porphyrins.

PMID- 18618565
TI  - Preferential solvation and hydrogen bonding in mixed solvents.

PMID- 18618566
TI  - Lateral association of cylindrical nanofibers into flat ribbons triggered by
      "molecular glue".

PMID- 18618567
TI  - Li2B12Si2: the first ternary compound in the system Li/B/Si: synthesis, crystal
      structure, hardness, spectroscopic investigations, and electronic structure.
AB  - We present the synthesis, crystal structure, hardness, IR/Raman and UV/Vis
      spectra, and FP-LAPW calculations of the electronic structure of Li(2)B(12)Si(2),
      the first ternary compound in the system Li/B/Si. Yellow, transparent single
      crystals were synthesized from the elements in tin as solvent at 1500 degrees C
      in h-BN crucibles in arc-welded Ta ampoules. Li(2)B(12)Si(2) crystallizes
      orthorhombic in the space group Cmce (no. 64) with a=6.1060(6), b=10.9794(14),
      c=8.4050(8) A, and Z=4. The crystal structure is characterized by a covalent
      network of B(12) icosahedra connected by Si atoms and Li atoms located in
      interstitial spaces. The structure is closely related to that of MgB(12)Si(2) and
      fulfils the electron-counting rules of Wade and Longuet-Higgins. Measurements of
      Vickers (H(V)=20.3 GPa) and Knoop microhardness (H(K)=20.4 GPa) revealed that
      Li(2)B(12)Si(2) is a hard material. The band gap was determined experimentally
      and calculated by theoretical means. UV/Vis spectra revealed a band gap of 2.27
      eV, with which the calculated value of 2.1 eV agrees well. The IR and Raman
      spectra show the expected oscillations of icosahedral networks. Theoretical
      investigations of bonding in this structure were carried out with the FP-LAPW
      method. The results confirm the applicability of simple electron-counting rules
      and enable some structural specialties to be explained in more detail.

PMID- 18618568
TI  - Homodinuclear ruthenium catalysts for dimer ring-closing metathesis.

PMID- 18618569
TI  - C1-(C84-C2(11))(CF3)12: trifluoromethylation yields structural proof of a minor
      C84 cage and reveals a principle of higher fullerene reactivity.

PMID- 18618570
TI  - An epilogue on the C78-fullerene family: the discovery and characterization of an
      elusive isomer.

PMID- 18618571
TI  - Self-assembly of a cavitand-based capsule by dynamic boronic ester formation.

PMID- 18618572
TI  - Interfacial organization of Y-shaped rod-coil molecules packed into cylindrical
      nanoarchitectures.
AB  - The behavior at the air/water interface and the structures of Langmuir-Blodgett
      monolayers at different surface pressures of rod-coil molecules, which consist of
      a Y-shaped rigid aromatic segment containing peripheral tetradecyloxy groups and
      a flexible poly(ethylene oxide) (PEO) chain with 17, 21, 34, or 45 repeating
      ethylene oxide units (Y17, Y21, Y34, and Y45), were investigated. For the Y21 and
      Y34 molecules, AFM images revealed two kinds of cylindrical nanoarchitectures
      formed upon compression. The nanostructured films were further investigated by
      UV/Vis and FTIR spectroscopy. The formation of the cylindrical nanoarchitectures
      was due to different tilting angles offered by the mismatch of the cross
      sectional areas of the PEO chain and the benzene ring with attached alkyl chains,
      and the different PEO contents of the molecules. The multiple pi-pi stacking and
      hydrophobic interactions provide exceptional stability of the nanostructures and
      allow them to be preserved in the course of flipping. For the shortest PEO chain
      of the Y17 molecule, spontaneous aggregation occurred. The Y45 molecule revealed
      the formation of 2D circular domains caused by entanglement of the longest PEO
      chains and coiling at the air/water interface. In addition, an interesting
      vortical morphology was obtained for the Y21 molecule upon deposition of the film
      onto a mica substrate, which indicates that the substrate chemistry also has an
      effect on the morphologies during the film-transfer process.

PMID- 18618573
TI  - Ruthenium(II) complexes for two-photon absorption-based optical power limiting.

PMID- 18618574
TI  - Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of
      advanced nonsmall cell lung cancer.
AB  - BACKGROUND: The purpose of the study was to investigate whether polymorphisms of
      p53 codon 72 (Arg72Pro) and MDM2 SNP309 (309T>G) affect p53 expression and the
      clinical outcome of patients with advanced nonsmall cell lung cancer (NSCLC).
      METHODS: A total of 148 NSCLC patients, previously enrolled in 2 different
      prospective clinical trials, were genotyped for the p53 Arg72Pro and MDM2 309T>G
      polymorphisms. Immunohistochemical staining of p53 protein was performed on 61
      tumor samples. Genotypes were correlated with p53 expression, clinicopathologic
      factors, tumor response, and survival. Multivariate logistic or Cox regression
      analyses were used to adjust for possible confounding variables. RESULTS: The
      distribution of sex, age, performance status, stage, tumor histology, and smoking
      habit was not significantly different among polymorphism variants. However, a
      significant association was observed between p53 Arg72Pro polymorphism and
      primary resistance to chemotherapy. Patients with the Pro/Pro variant were more
      likely to be resistant to first-line chemotherapy, especially the irinotecan plus
      cisplatin regimen, than those with Arg/Arg or Arg/Pro variants (60% vs 27%, P =
      .014). In multivariate analysis, the Pro/Pro genotype was strongly predictive for
      shorter progression-free survival (PFS) (hazard ratio [HR] = 1.952, P = .01). The
      p53 overexpression was associated with MDM2 SNP309. The TT genotype showed more
      p53 overexpression than TG or GG genotypes (P = .036). In multivariate analysis,
      the MDM2 TT genotype was independently predictive for longer survival (HR =
      1.742, P = .032). CONCLUSIONS: The p53 72Pro/Pro variant was predictive for
      primary resistance to chemotherapy and shorter progression-free survival. The
      MDM2 SNP309 was associated with less p53 overexpression and prognostic for worse
      survival. Genotyping these polymorphisms may be useful for predicting the
      clinical outcome of advanced NSCLC.

PMID- 18618575
TI  - Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the
      cadherin-associated protein beta1 gene CTNNB1 for patients with Wilms tumors:
      results of long-term surveillance of 71 patients from International Society of
      Pediatric Oncology Study 9/Society for Pediatric Oncology.
AB  - BACKGROUND: Mutations in the Wilms tumor (WT) suppressor 1 gene (WT1) and the
      cadherin-associated protein beta1 gene (CTNNB1) are found predominantly in
      stromal type WT, defining a genetic subgroup. The clinical relevance of these
      mutations remains to be determined. METHODS: A long-term follow-up study was
      performed for 71 patients (International Society of Pediatric Oncology Study
      9/Society for Pediatric Oncology; n = 77 tumors) with known molecular genetic
      status. Eight patients had bilateral disease, including 2 patients with a WT in
      both kidneys and 5 patients with a WT in 1 kidney and nephrogenic rests (NRs) in
      the other kidney. The response to preoperative chemotherapy, relapses,
      metastases, metachronous tumor development, and deaths were evaluated with a
      median follow-up of 12 years and 4 months. RESULTS: Nineteen patients (n = 24
      tumors) had WT1 mutations, and 16 were constitutional mutations. Three patients
      with germline mutations had second tumor events: Two patients developed a WT in
      the kidney with NRs 3 years and 11 years after the first tumor; and 1 patient
      developed second tumors after 2 years, 1 in the kidney with a previous WT and 1
      in the kidney with a previous NR. Eighteen of the WT1 mutant tumors were analyzed
      for CTNNB1 mutations, and all had mutations. A poor volumetric response
      (progression and <50% reduction) was observed in all patients who had tumors with
      a WT1 mutation and in 23 of 52 nonmutant tumors. CONCLUSIONS: Patients with WT1
      germline mutations had an increased risk for bilateral disease and second tumor
      events. Therefore, the authors concluded that tumor surveillance until adulthood
      should be considered. Although tumors with both WT1 and CTNNB1 mutations had a
      poor volumetric response, there was no significant difference in overall survival
      in this cohort of patients with and without WT1 mutations.

PMID- 18618576
TI  - Novel 2-step synthetic indole compound 1,1,3-tri(3-indolyl)cyclohexane inhibits
      cancer cell growth in lung cancer cells and xenograft models.
AB  - BACKGROUND: The clinical responses to chemotherapy in lung cancer patients are
      unsatisfactory. Thus, the development of more effective anticancer drugs for lung
      cancer is urgently needed. METHODS: A 2-step novel synthetic compound, referred
      to as 1,1,3-tri(3-indolyl)cyclohexane (3-indole), was generated in high purity
      and yield. 3-Indole was tested for its biologic activity in A549, H1299, H1435,
      CL1-1, and H1437 lung cancer cells. Animal studies were also performed. RESULTS:
      The data indicate that 3-indole induced apoptosis in various lung cancer cells.
      Increased cytochrome-c release from mitochondria to cytosol, decreased expression
      of antiapoptotic Bcl-2, and increased expression of proapoptotic Bax were
      observed. In addition, 3-indole stimulated caspases-3, -9, and to a lesser extent
      caspase-8 activities in cancer cells, suggesting that the intrinsic mitochondria
      pathway was the potential mechanism involved in 3-indole-induced apoptosis. 3
      Indole-induced a concentration-dependent mitochondrial membrane potential
      dissipation and an increase in reactive oxygen species (ROS) production.
      Activation of c-Jun N-terminal kinase (JNK) and triggering of DNA damage were
      also apparent. Note that 3-indole-induced JNK activation and DNA damage can be
      partially suppressed by an ROS inhibitor. Apoptosis induced by 3-indole could be
      abrogated by ROS or JNK inhibitors, suggesting the importance of ROS and JNK
      stress-related pathways in 3-indole-induced apoptosis. Moreover, 3-indole showed
      in vivo antitumor activities against human xenografts in murine models.
      CONCLUSIONS: On the basis of its potent anticancer activity in cell and animal
      models, the data suggest that this 2-step synthetic 3-indole compound of high
      purity and yield is a potential candidate to be tested as a lead pharmaceutical
      compound for cancer treatment.

PMID- 18618577
TI  - Care and parentage in a skin-feeding caecilian amphibian.
AB  - An exceptional form of parental care has recently been discovered in a poorly
      known caecilian amphibian. Mothers of the Taita Hills (Kenya) endemic
      Boulengerula taitanus provide their own skin as a food source for their
      offspring. Field data suggest that nursing is costly. Females found attending
      young had a lower body condition and fat body volume than nonbrooding and egg
      incubating females, and the female condition decreased substantially during
      parental care. Most mothers and their eggs or offspring were found in close
      proximity to other nesting females, in high-density nest sites that enhance the
      potential for social interactions and highlighting the possibility of communal
      breeding. Parentage was investigated using Amplified Fragment Length Polymorphism
      (AFLP) genetic markers in 29 offspring from six litters guarded by putative
      mothers. Our data provide the first evidence of multiple paternity in a
      caecilian, implying that two fathers sired one litter. Some young from two
      litters had genotypes not matching the guarding female suggesting that not all
      offspring are cared for by their biological mothers. This study provides evidence
      for alloparenting in an amphibian with cost-intensive parental care.

PMID- 18618578
TI  - Upstaging benefits and accuracy of sentinel lymph node mapping in colorectal
      adenocarcinoma nodal staging.
AB  - BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) mapping is an additional
      method for improving colorectal cancer nodal staging. The purpose of the study
      was to define the method's accuracy in nodal staging, its upstaging benefits and
      to identify the predictive factors for its failure. METHODS: Lymphatic mapping
      was performed using technetium-99m-phytate and patent blue in 52 consecutive
      colorectal adenocarcinoma patients. Enhanced pathological examination was carried
      out on SLNs with hematoxylin-eosin step-sectioning and immunochemistry. RESULTS:
      The patients studied had an average tumor size of 6.5 cm; 85% had T3/T4 tumors;
      and rectal tumors represented 57.7% of the group. Overall SLN mapping accuracy
      was 79.5%, with sensitivity of 65.2% and 34.8% false negatives. Upstaging with
      SLN mapping was 23.1%. Colon tumors had an SLN identification rate of 90.9% and
      rectal tumors had 63.3% (P = 0.023). Multivariate statistical analysis identified
      lower rectal tumor (P = 0.009), neoadjuvant treatment (P = 0.029) and tumor size
      (P = 0.036) as independent risk factors for the inability to detect SLNs.
      CONCLUSIONS: Upstaging benefits of SLN mapping should be considered in colon and
      mid- and upper rectal tumors. The method should be avoided in patients with lower
      rectal tumors, large tumors and having had neoadjuvant therapy.

PMID- 18618579
TI  - Aggressiveness of care in a prospective cohort of patients with advanced NSCLC.
AB  - BACKGROUND: Optimal end of life care of patients with terminal cancer is poorly
      understood. In this study, the aggressiveness of care is described in a cohort of
      patients with newly diagnosed advanced nonsmall-cell lung cancer (NSCLC).
      METHODS: Patients within 8 weeks of diagnosis of stage IIIb (with effusions) or
      IV NSCLC were enrolled in a study to examine the feasibility of involving
      palliative care services early in the provision of cancer care. Participants
      received standard oncology treatment and integrated palliative care. All patients
      were followed prospectively to assess anticancer therapy usage, hospital
      admissions, hospice utilization, and location of death. RESULTS: At the time of
      analysis, 40/46 (87%) of enrolled patients had died, with a median length of
      follow-up of 29.3 months. Aggressive care measures in the final month of life
      included rates of anticancer therapy (40%), emergency department visits (48%),
      and hospital admissions (50%). Sixty-five percent of patients received hospice
      care before death, with a median length of stay of 16 days. Patients with
      heightened baseline anxiety and mood symptoms were more likely to receive
      anticancer therapy at the end of life compared with those without such symptoms.
      CONCLUSIONS: This study demonstrates the frequent use of aggressive measures at
      the end of life among patients with advanced NSCLC in a tertiary care center, as
      shown by the number of patients receiving anticancer therapy within 30 days of
      death and brief utilization of hospice services. Further research is needed to
      identify predictors of aggressive care and to develop interventions enhancing
      decision-making at the end of life.

PMID- 18618580
TI  - Invasive tumor cells and prognosis in a selected population of patients with
      glioblastoma multiforme.
AB  - BACKGROUND: After surgical resection, the residual, invasive glioblastoma (GBM)
      cells give rise to a recurrent tumor, which, in 96% of patients, arises adjacent
      to the resection margin. METHODS: In this study, the authors prospectively
      enrolled 25 patients with GBM who underwent gross total resection followed by
      adjuvant radiochemotherapy (with temozolomide). Tumor removal was achieved with
      resection margins that included the neighboring, apparently normal tissue
      (between 1 cm and 2 cm from the tumor border [B area]) and the tumor. RESULTS:
      Patients who had an absence of tumor cells in the neighboring, apparently normal
      white matter (B area) had better survival than patients who had the presence of
      tumor cells in the B area (21 months vs 12 months). This difference was
      statistically significant in univariate analysis (P = .005) and in multivariate
      analysis (P = .01). CONCLUSIONS: Aggressive tumor removal may improve survival,
      but the current results indicated that biologic commitment of 'penumbra' cells
      appear to be the most relevant factor for tumor recurrence and accounts for the
      fatal outcome of the disease.

PMID- 18618581
TI  - Screening and referral for psychosocial distress in oncologic practice: use of
      the Distress Thermometer.
AB  - BACKGROUND: The objectives of this study were to validate the Distress
      Thermometer (DT) in the Netherlands and to examine its correspondence with a 46
      item Problem List, possible risk factors, and the wish for a referral. METHODS: A
      cross-sectional group of 277 cancer patients who were treated at 9 hospitals
      filled in the DT and the Hospital Anxiety and Depression Scale and rated the
      presence and severity of problems (response rate, 49%). RESULTS: Receiver
      operating characteristic analyses identified an ideal cutoff score of 5 on the DT
      with a positive predictive value of 39% and a negative predictive value of 95%.
      The Problem List appeared to be a reliable measure. Five items on the Problem
      List correlated strongly with the DT, 13 items had a moderately strong
      correlation, 26 items were correlated weakly, and 2 items were not correlated
      significantly. Emotional control, nervousness, pain, and physical fitness
      appeared to contribute independently to the DT score. The percentage of patients
      scoring > or =5 (n = 118 patients; 43%) who wanted (14%) or maybe wanted (29%) a
      referral was significantly higher than the percentage of patients with DT scores
      <5 (5% and 13%, respectively) who wanted or maybe wanted a referral. Intensively
      treated patients reported more distress than those who only underwent surgery. No
      other clear risk factors for distress were identified. CONCLUSIONS: The DT
      appeared to be a good instrument for routine screening and ruling out elevated
      distress. Emotional and physical problems contributed mainly to distress.
      Experiencing clinically elevated distress did not necessarily suggest that
      patients wanted a referral. Screening for distress and the wish for a referral
      can facilitate providing support for those patients who most need and want it.

PMID- 18618582
TI  - Effects of low dose radiation and vitamin C treatment on chloroquine-induced
      genotoxicity in mice.
AB  - Chloroquine (CHQ) is a commonly used antimalarial agent. We evaluated the
      genotoxic potential of CHQ using chromosome aberration (CA), micronucleus (MN),
      and sperm head abnormality (SA) assays in vivo in Swiss albino mice. The
      interaction between a low dose of radiation and CHQ, as well as the effect of
      vitamin C on CHQ-induced genotoxicity, was also evaluated. It was observed that
      CHQ induced CA, as well as MN, in the bone marrow cells under certain treatment
      conditions. Further, CHQ induced significant increase in the frequency of SA both
      at 24 hr and 21 days of the treatment. In the present study vitamin C
      pretreatment apparently reduced the frequency of CA, MN, and SA induced by CHQ.
      In the combination studies with radiation and CHQ, we found that exposure to low
      doses of radiation (0.5 Gy) either prior to or following CHQ treatment, in the
      dose ranges tested, has little or no synergistic effect in the mutagenic
      evaluations in somatic cells. However, radiation exposure along with CHQ
      treatment resulted in significant increase in the frequency of SA as compared to
      the groups receiving CHQ alone at 21 days of the treatment. In summary, CHQ has
      the potential to induce genotoxicity in mammalian cells. Further, germ cells may
      be relatively more sensitive as compared to the somatic cells.

PMID- 18618583
TI  - Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled
      carbon nanotubes and C(60) fullerenes in the FE1-Mutatrade markMouse lung
      epithelial cells.
AB  - Viability, cell cycle effects, genotoxicity, reactive oxygen species production,
      and mutagenicity of C(60) fullerenes (C(60)) and single-walled carbon nanotubes
      (SWCNT) were assessed in the FE1-Mutatrade markMouse lung epithelial cell line.
      None of these particles induced cell death within 24 hr at doses between 0 and
      200 microg/ml or during long-term subculture exposure (576 hr) at 100 microg/ml,
      as determined by two different assays. However, cell proliferation was slower
      with SWCNT exposure and a larger fraction of the cells were in the G1 phase.
      Exposure to carbon black resulted in the greatest reactive oxygen species
      generation followed by SWCNT and C(60) in both cellular and cell-free particle
      suspensions. C(60) and SWCNT did not increase the level of strand breaks, but
      significantly increased the level of FPG sensitive sites/oxidized purines (22 and
      56%, respectively) determined by the comet assay. The mutant frequency in the cII
      gene was unaffected by 576 hr of exposure to either 100 microg/ml C(60) or SWCNT
      when compared with control incubations, whereas we have previously reported that
      carbon black and diesel exhaust particles induce mutations using an identical
      exposure scenario. These results indicate that SWCNT and C(60) are less genotoxic
      in vitro than carbon black and diesel exhaust particles.

PMID- 18618584
TI  - Recent advances in research relevant to electric and magnetic field exposure
      guidelines.
AB  - Limits on exposures to extremely low-frequency electric fields, magnetic fields
      and contact currents, designated as voluntary guidelines or standards by several
      organizations worldwide, are specified so as to minimize the possibility of
      neural stimulation. The limits, which we refer to as guidelines, derive from
      "basic restrictions" either on electric fields or current density within tissue,
      or on avoidance of annoying or startling interactions that may be experienced
      with spark discharge or contact current. Further, the guidelines specify more
      conservative permissible doses and exposure levels for the general public than
      for exposures in controlled environments, which most typically involve
      occupational settings. In 2001 we published an update on guideline science. This
      paper covers more recent developments that are relevant to the formulation and
      implementation of the next generation of guidelines. The paper deals with
      neurostimulation thresholds and the relevance of magnetophosphenes to setting
      guideline levels; dosimetry associated with contact current benchmarked against
      basic restrictions; tissue and cellular dosimetry from spark discharge;
      assessment of exposures to high electric fields in realistic situations (e.g.,
      line worker in a transmission tower); a simplified approach to magnetic field
      assessment in non-uniform magnetic fields; and a quantitative approach to
      sampling workplace exposure for assessing compliance.

PMID- 18618585
TI  - Morphological analyses and 3D modeling of the tongue musculature of the
      chimpanzee (Pan troglodytes).
AB  - Knowledge of the comparative anatomy of tongue musculature is crucial to the
      discussion of the origin and the evolution of speech because of the indispensable
      role played by this organ in speech. However, the tongue musculature of primates
      has rarely been studied. In a previous study, the author analyzed human tongue
      musculature and developed a 3D model of this organ [Takemoto, Journal of Speech,
      Language, and Hearing Research 44:95-107, 2001]. In this study, the tongue
      musculature of chimpanzees was examined using methods similar to those used for
      humans. Results showed that tongue musculature was topologically the same for
      both humans and chimpanzees. As in humans, the tongue musculature of chimpanzees
      consisted of inner and outer regions. The inner musculature was composed of
      serial "structural units," made up of two types of laminae whose fibers were
      perpendicular to the tongue surface. The outer musculature was a thin layer of
      fibers oriented parallel to the surface and superficial to the inner musculature.
      Although the tongue musculature of humans and chimpanzees is similar, the
      external shapes differ: the chimpanzee tongue is flat, whereas the human tongue
      is round. Applying the muscular hydrostat theory to the external shape of the
      tongue suggests that the primary actions of the chimpanzee tongue are protrusion
      and retrusion, whereas the human tongue can be deformed in the oral cavity with a
      high degree of freedom. It is hypothesized that the evolution of the external
      shape of the tongue is one of the factors that led to the development of human
      speech. The results of this study suggest that modeling based on muscular
      hydrostatic theory of the effects of changes in external tongue shape on
      articulatory movements should be included in discussions on the origin of speech.

PMID- 18618586
TI  - Extra-nuclear signaling of estrogen receptors.
AB  - Estrogen controls multiple biological functions through binding to estrogen
      receptors (ERs). Traditionally, ERs have been regarded as transcription factors
      regulating the expression of target genes. However, growing evidence of rapid
      estrogen's actions in a number of tissues has been accumulating and alternative
      mechanisms of signal transduction have been proposed. These so called "extra
      nuclear actions" do not require gene expression or protein synthesis and are
      independent of the nuclear localization of ERs. Indeed, some of these actions are
      elicited by ERs residing at or near the plasma membrane. Membrane-associated
      molecules such as ion channels, G proteins, the tyrosine kinase c-Src as well as
      growth factor receptors are modulated by liganded ERs within the membrane,
      leading to the activation of downstream cascades such as mitogen-activated
      protein kinase, phosphatidylinositol 3-OH kinase, protein kinase A, and protein
      kinase C. These cascades mediate some important rapid actions of estrogen, such
      as the activation of nitric oxide synthesis or the remodeling of actin
      cytoskeleton. In addition, these pathways are critical for the regulation of the
      expression of a number of target proteins implicated in cell proliferation,
      apoptosis, differentiation, movement, and homeostasis. In this manner, the extra
      nuclear pathways are tightly integrated with the genomic pathways to orchestrate
      the full spectrum of estrogen's biological functions. The recent advancements in
      the characterization of the molecular basis of the extra-nuclear signaling of
      estrogen helps to understand the role of estrogen on human cells, and may in
      future turn out to be of relevance for clinical purposes.

PMID- 18618588
TI  - Caveolin-1 promotes the transformation and anti-apoptotic ability of mouse
      hepatoma cells.
AB  - Caveolin-1 is a major structural protein of caveolae and plays important roles in
      signal transduction, cellular transformation and tumor metastasis. Our previous
      study demonstrated that caveolin-1 expression level was positively correlated
      with the invasive ability of mouse hepatoma Hepa1-6 and Hca-F cells. However, the
      role of caveolin-1 in cellular transformation and apoptosis remains undetermined.
      We found that exogenous expression of caveolin-1 in Hepa1-6 cells enhanced cell
      transformation capability both in vitro and in vivo and prevented actinomycin D
      induced apoptosis via the activation of survivin-mediated survival pathway.
      Conversely, downregulation of caveolin-1 in Hca-F cells significantly attenuated
      cell transformation ability in vitro and in vivo and increased cell sensitivity
      to actinomycin D by inhibiting survivin-mediated survival pathway. These results
      indicate that caveolin-1 could play an active role in mediating the
      transformation and survival of mouse hepatoma cells and might be a potential
      target for gene and antitumor drugs therapy.

PMID- 18618587
TI  - Cloning and characterization of E-dlg, a novel splice variant of mouse homologue
      of the Drosophila discs large tumor suppressor binds preferentially to SAP102.
AB  - Membrane-associated guanylate kinases (MAGUKs) act as scaffolds to coordinate
      signaling events through their multiple domains at the plasma membrane. The MAGUK
      SH3 domain is noncanonical and its function remains unclear. To identify
      potential binding partners of MAGUK SH3, the synapse-associated protein 102
      (SAP102) SH3 domain was used as bait in a yeast two-hybrid screen of a mouse
      embryonic cDNA library. A mouse homologue of the Drosophila discs large tumor
      suppressor (Dlg, also known as SAP97) bound preferentially to SAP102 SH3. The
      4347bp cDNA sequence encoded an 893 amino acid protein with 94% identity to mouse
      SAP97. A deleted region (33-aa) strongly suggests this is a novel splice variant,
      which we call Embryonic-dlg/SAP97 (E-dlg). The interaction of SAP102 and E-dlg
      was confirmed in mammalian cells. E-dlg can also bind to potassium channel Kv1.4
      in a pull-down assay. E-dlg was highly expressed in embryonic and some adult
      mouse tissues, such as brain, kidney, and ovary. Furthermore, in situ
      hybridization showed that E-dlg was mostly expressed in olfactory bulb and
      cerebellum.

PMID- 18618589
TI  - Self-aggregation of water-soluble chitosan and solubilization of thymol as an
      antimicrobial agent.
AB  - Water-soluble chitosan (WCS) with five different molecular weights was
      synthesized by N-acetylation of chitosan with acetic anhydride. Degree of
      deacetylation of sample was determined by potentiometric titration. The structure
      of WCS was characterized by FTIR, XRD, and gel permeation chromatography. The
      critical aggregation concentration (cac) of self-aggregation was determined by
      measuring the fluorescence intensity of pyrene as a fluorescent probe and the
      surface tension. With the decrease of weight-average molecular weight (M(w)), the
      cac values of WCSs in aqueous media were 0.48, 0.41, 0.35, 0.16, and 0.06 mg/mL,
      respectively. The surface tension-concentration plots of WCS5 had more than one
      turning point. It showed WCS had tendency to form monomolecular micelles in the
      very dilute solutions. In addition, WCSs were evaluated for efficacy of
      nanoparticle formation, which can solubilize and carry thymol, a water-insoluble
      antimicrobial agent. The diameter and morphology of thymol-loaded WCS
      nanoparticles were characterized by Zeta size nano series and TEM. Mean diameters
      of these thymol-loaded WCS nanoparticles in aqueous media were 189, 167, 134, 35,
      and 21 nm, respectively. TEM photographs exhibited the thymol-loaded WCS
      nanoparticle as a bimolecular micelle. Furthermore, thymol-loaded WCS
      nanoparticles had stronger antibacterial activity than thymol. With the decrease
      of the size, the thymol-loaded nanoparticles showed a stronger antimicrobial
      effect on gram-positive bacteria and fungi. The minimum inhibitory concentration
      value of thymol-loaded WCS5 nanoparticle against Staphyococcus aureus and
      Bacillus subtilis was 0.00313-0.00157% (w/v).

PMID- 18618590
TI  - Lessons learned from the Oklahoma thrombotic thrombocytopenic purpura-hemolytic
      uremic syndrome registry.
AB  - The Oklahoma TTP-HUS Registry provides a complete community perspective of
      thrombotic thrombocytopenic purpura (TTP). This is possible because plasma
      exchange is the essential treatment for TTP and the Oklahoma Blood Institute
      provides all plasma exchange procedures for a region encompassing most of the
      State, including 58 of Oklahoma's 77 counties. The Registry is an inception
      cohort of consecutive patients for whom plasma exchange treatment was requested
      for a diagnosis of either TTP or hemolytic uremic syndrome (HUS). All 382
      patients identified from January 1, 1989 to December 31, 2007 have consented to
      be enrolled. Complete follow-up is available for 380 of 382 patients. Patients
      are described both by clinical categories, related to their associated conditions
      and clinically apparent etiologies, and by the presence of severe ADAMTS13
      deficiency. ADAMTS13 activity has been measured on 235 (93%) of 254 patients
      since 1995. Registry data have provided new perspectives on the definition and
      diagnoses of these syndromes as well as their outcomes. Long-term follow-up has
      documented that relapse is common among patients with ADAMTS13 deficiency but
      rarely occurs in patients without ADAMTS13 deficiency. Long-term follow-up has
      also documented persistent abnormalities of health-related quality-of-life and
      cognitive function. In addition to providing new perspectives on the natural
      history of these syndromes, The Oklahoma TTP-HUS Registry provides a support
      group for our patients, information about evaluation and management for community
      physicians, and a resource for research and educational programs.

PMID- 18618591
TI  - Rad51 overexpression rescues radiation resistance in BRCA2-defective cancer
      cells.
AB  - Breast cancers with BRCA2 mutations exhibit DNA repair defects and are
      particularly sensitive to radiation. BRCA2 interacts with Rad51 in a complex
      manner involving internal BRC and C-terminal TR2 domains which play a key role in
      homologous recombination. BRCA2 expression also modulates Rad51 protein levels
      such that Rad51 protein is relatively decreased in BRCA2-defective cancer cells.
      This is mediated in part through BRCA2's capacity to protect Rad51 from caspase-3
      proteolytic degradation. In order to distinguish between functional and
      expression related roles for BRCA2 we studied the results of Rad51 overexpression
      in mouse and human cells with inactivating BRCA2 mutations. The results show that
      overexpression of wild-type Rad51 partially rescues BRCA2 deficiency but that
      overexpression of a caspase-3 resistant Rad51 completely complements the BRCA2
      defect in radiation responsiveness. These results indicate that Rad51 can
      compensate for some aspects of a BRCA2 gene defect and suggest that Rad51
      expression levels may be an important modifier of the BRCA2 defective genotype.

PMID- 18618592
TI  - Cytochrome P450 1B1 expression in rat esophageal tumorigenesis promoted by
      gastric and duodenal reflux.
AB  - Cytochrome P450 1B1 (CYP1B1) mRNA is constitutively expressed in most normal
      extra-hepatic tissues; however the protein is not detectable in these tissues but
      is expressed in a wide variety of tumors. CYP1B1 is responsible for the
      activation of a number of carcinogens present in tobacco smoke and food. A
      surgical model of rat esophageal tumorigenesis, promoted by gastric or duodenal
      reflux was used to determine CYP1B1 expression in premalignant esophageal tissue.
      Immunohistochemistry was performed using a modified amplified fluorescein
      tyramide protocol. CYP1B1 was not observed in normal esophageal mucosa,
      submucosa, or muscularis mucosa. Animals exposed to gastric reflux developed mild
      hyperplasia. Varying degrees of hyperplasia were observed in the duodenal reflux
      group. All regions of hyperplasia showed moderate or strong CYP1B1
      immunoreactivity. Duodenal reflux induced a small number of premalignant changes:
      immunoreactivity was absent from the epithelium of squamous dysplasia (0/10),
      Barrett's esophagus (0/7), and majority of dysplastic Barrett's esophagus (1/4).
      Moderate or strong immunoreactivity was observed in the majority (7/8) of
      squamous cell carcinomas (SCCs) in situ. Immunoreactivity was also observed in
      the lamina propria and submucosa in association with inflammation, regardless of
      the severity of inflammation. The expression of CYP1B1 in hyperplasia, SCCs in
      situ, or in association with inflammation may increase the production of
      carcinogenic metabolites, which may promote esophageal tumorigenesis.

PMID- 18618594
TI  - In situ immunocytochemical detection of altered membrane composition induced by
      cell-cell contact in cultured mammalian cells.
AB  - In cultured mammalian cells, both normal and transformed, cell-cell contact was
      shown to alter the detergent extractability of nuclear and plasma membranes
      detected using immunocytochemistry of fixed cells. This alteration occurred in
      each cell individually, occurred in less than 1 hour after altered cell-cell
      contact, and did not involve new protein or mRNA synthesis. These results
      indicate that composition of cellular membranes is highly affected by cell-cell
      contact and culture density. This suggests a possible role for alterations in
      membrane composition in the regulation of normal cell behavior, including
      signaling of contact inhibition of growth and movement, behaviors that are not
      effectively regulated by cell-cell contact in malignantly transformed cells.

PMID- 18618595
TI  - Mutagenic potential of nitrenium ions of nitrobenzanthrones: correlation between
      theory and experiment.
AB  - The mutagenic activity of nine substituted nitrobenzanthrone (NBA) derivatives
      was recently established in the Ames assay and ranged from near inactivity to
      extremely high mutagenic activity (Takamura-Enya et al. 2006: Mutagenesis 21:399
      404). Using thermochemical and molecular modeling techniques, the activation
      pathway of these NBA derivatives, namely 1-nitro-, 2-nitro-, 3-nitro-, 9-nitro-,
      11-nitro-, 1,9-dinitro-, 3,9-dinitro-, 3,11-dinitro-, and 3,9,11
      trinitrobenzanthrone, and the formation of the corresponding aryl-nitrenium ions,
      were investigated using density functional theory calculations. The calculated
      properties of the NBA derivatives were systematically compared with their
      bacterial mutagenic potency. Accommodation of the ligand substrates into the
      binding pocket of the bacterial nitroreductases was not sterically inhibited for
      the NBAs. Moreover, electron affinities, water elimination energies,
      esterification, and solvolysis energies did not reveal any possible links with
      the observed mutagenic potency of the NBAs. However, a strong negative linear
      correlation was found when the relative energies of the nitrenium ions of the
      mono and disubstituted NBAs were plotted against the logarithm of the mutagenic
      potency of the NBAs found in the different Salmonella typhimurium strains.
      Therefore, our data clearly indicate that the stability of the nitrenium ions is
      one critical determinant of the mutagenic potency of NBAs in Salmonella tester
      strains.

PMID- 18618593
TI  - Association of single nucleotide polymorphisms in a glutamate receptor gene
      (GRM8) with theta power of event-related oscillations and alcohol dependence.
AB  - Evidence suggests the P3 amplitude of the event-related potential and its
      underlying superimposed event-related oscillations (EROs), primarily in the theta
      (4-5 Hz) and delta (1-3 Hz) frequencies, as endophenotypes for the risk of
      alcoholism and other disinhibitory disorders. Major neurochemical substrates
      contributing to theta and delta rhythms and P3 involve strong GABAergic,
      cholinergic and glutamatergic system interactions. The aim of this study was to
      test the potential associations between single nucleotide polymorphisms (SNPs) in
      glutamate receptor genes and ERO quantitative traits. GRM8 was selected because
      it maps at chromosome 7q31.3-q32.1 under the peak region where we previously
      identified significant linkage (peak LOD = 3.5) using a genome-wide linkage scan
      of the same phenotype (event-related theta band for the target visual stimuli).
      Neural activities recorded from scalp electrodes during a visual oddball task in
      which rare target elicited P3s were analyzed in a subset of the Collaborative
      Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian
      subjects from 209 families (with 472 DSM-IV alcohol dependent individuals). The
      family-based association test (FBAT) detected significant association (P < 0.05)
      with multiple SNPs in the GRM8 gene and event-related theta power to target
      visual stimuli, and also with alcohol dependence, even after correction for
      multiple comparisons by false discovery rate (FDR). Our results suggest that
      variation in GRM8 may be involved in modulating event-related theta oscillations
      during information processing and also in vulnerability to alcoholism. These
      findings underscore the utility of electrophysiology and the endophenotype
      approach in the genetic study of psychiatric disorders.

PMID- 18618596
TI  - Pharmacokinetics, dose-range, and mutagenicity studies of methylphenidate
      hydrochloride in B6C3F1 mice.
AB  - Methylphenidate hydrochloride (MPH) is one of the most frequently prescribed
      pediatric drugs for the treatment of attention deficit hyperactivity disorder. In
      a recent study, increased hepatic adenomas were observed in B6C3F1 mice treated
      with MPH in their diet. To evaluate the reactive metabolite, ritalinic acid (RA)
      of MPH and its mode of action in mice, we conducted extensive investigations on
      the pharmacokinetics (PK) and genotoxicity of the drug in B6C3F1 mice. For the PK
      study, male B6C3F1 mice were gavaged once with 3 mg/kg body weight (BW) of MPH
      and groups of mice were sacrificed at various time points (0.25-24 hr) for serum
      analysis of MPH and RA concentrations. Groups of male B6C3F1 mice were fed diets
      containing 0, 250, 500, 1,000, 2,000, or 4,000 ppm of MPH for 28 days to
      determine the appropriate doses for 24-week transgenic mutation studies. Also,
      the micronucleus frequencies (MN-RETs and MN-NCEs), and the lymphocyte Hprt
      mutants were determined in peripheral blood and splenic lymphocytes,
      respectively. Mice fed 4,000 ppm of MPH lost significant BW compared to control
      mice (P < 0.01). There was a significant increase in the average liver weights
      whereas kidneys, seminal vesicle, testes, thymus, and urinary bladder weights of
      mice fed higher doses of MPH were significantly lower than the control group (P <
      or = 0.05). There was no significant increase in either the Hprt mutant frequency
      or the micronucleus frequency in the treated animals. These results indicated
      that although MPH induced liver hypertrophy in mice, no genotoxicity was
      observed.

PMID- 18618597
TI  - Unilateral ovariectomy increases egg size and reduces follicular atresia in the
      semelparous coho salmon, Oncorhynchus kisutch.
AB  - Unilateral ovariectomy (ULO, removal of one ovary) is a powerful technique for
      studying aspects of reproductive physiology, including follicular recruitment and
      growth. To examine effects of ULO for the first time in a semelparous species,
      coho salmon (Oncorhynchus kisutch) were unilaterally ovariectomized during mid
      vitellogenesis approximately 3 months before spawning. At termination of the
      study (79 days post-surgery), single ovaries of ULO fish were gravimetrically
      equivalent to paired ovaries of sham surgery, control fish. There was no evidence
      of recruitment of new vitellogenic follicles. Instead, the dramatic increase in
      ovary mass was attributable to hypertrophy of existing vitellogenic follicles
      (33% increase in volume) and increased fecundity achieved through a greater than
      two-fold reduction in follicular atresia. The composition of whole ovaries on a
      dry weight basis from ULO fish was greater in protein, but lower in lipid than
      that of control fish. Expressing the data on a per follicle basis, however,
      showed that follicles of ULO fish contained more protein, ash, water, and lipid.
      The results indicate that ULO of coho salmon induces compensatory hypertrophy of
      existing vitellogenic follicles, while maximizing fecundity through reduction of
      atresia. Thus, 3 months before spawning, coho salmon exhibit the ability to
      adjust final egg size and number when faced with significant depletion of ovarian
      follicles. This in vivo system provides a platform for further study of
      physiological mechanisms regulating follicular growth and atresia, and the trade
      off between egg size and egg number.

PMID- 18618598
TI  - Women's global health.

PMID- 18618600
TI  - Local variability in PTC thermistor grain boundary structures.
AB  - Scanning electron microscopy-based conductive mode (CM) microscopy, using the
      remote electron beam-induced current configuration, was carried out on a positive
      temperature coefficient of resistance thermistor at temperatures below and above
      the Curie temperature, T(C). Below T(C), when the thermistor is in a low
      resistance state, no strong CM contrast was observed. Above T(C) the thermistor
      grain boundaries become highly resistive and significant CM contrast formed owing
      to three mechanisms: all of the areas that were studied showed resistive
      contrast, but in addition some grain boundaries showed additional contrast due to
      electron beam-induced current, the origin of which was consistent with the
      presence of a back-to-back Schottky barrier structure at the grain boundary.
      Other grain boundaries exhibited additional contrast owing to beta-conductivity,
      which suggests a slightly different n-i-n grain boundary structure at these
      interfaces. These results suggest that electrically active grain boundaries with
      different structures coexist within the thermistor.

PMID- 18618601
TI  - Testing for a historical population bottleneck in wild Verreaux's sifaka
      (Propithecus verreauxi verreauxi) using microsatellite data.
AB  - The degree to which historical human activities negatively impacted past and
      present lemur species is a long-standing question in primatology. At present,
      most evidence addressing this issue comes from archaeology, paleontology, and
      behavioral studies. Genetic data provide another source of evidence. In this
      study, six microsatellite loci, genotyped on more than 360 wild Verreaux's
      sifaka, are used in order to test the hypothesis that this population experienced
      a population bottleneck in the last 2000 years. Excess heterozygosity is compared
      with the heterozygosity expected under mutation-drift equilibrium in order to
      test for the genetic signature of a rapid population contraction in the past. The
      results indicate that the sifaka population did not experience a population
      bottleneck. Various methodological and conceptual implications of this result are
      discussed.

PMID- 18618599
TI  - Molecular mechanisms of Nrf2-mediated antioxidant response.
AB  - Nrf2 is the key transcription factor regulating the antioxidant response. Nrf2
      signaling is repressed by Keap1 at basal condition and induced by oxidative
      stress. Keap1 is recently identified as a Cullin 3-dependent substrate adaptor
      protein. A two-sites binding "hinge & latch" model vividly depicts how Keap1 can
      efficiently present Nrf2 as substrate for ubiquitination. Oxidative perturbation
      can impede Keap1-mediated Nrf2 ubiquitination but fail to disrupt Nrf2/Keap1
      binding. Nrf2 per se is a redox-sensitive transcription factor. A new Nrf2
      mediated redox signaling model is proposed based on these new discoveries. Free
      floating Nrf2 protein functions as a redox-sensitive probe. Keap1 instead
      functions as a gate keeper to control the availability of Nrf2 probes and thus
      regulates the overall sensitivity of the redox signaling.

PMID- 18618602
TI  - Physical properties of palm fruits processed with tools by wild bearded capuchins
      (Cebus libidinosus).
AB  - Habitually, capuchin monkeys access encased hard foods by using their canines and
      premolars and/or by pounding the food on hard surfaces. Instead, the wild bearded
      capuchins (Cebus libidinosus) of Boa Vista (Brazil) routinely crack palm fruits
      with tools. We measured size, weight, structure, and peak-force-at-failure of the
      four palm fruit species most frequently processed with tools by wild capuchin
      monkeys living in Boa Vista. Moreover, for each nut species we identify whether
      peak-force-at-failure was consistently associated with greater weight/volume,
      endocarp thickness, and structural complexity. The goals of this study were (a)
      to investigate whether these palm fruits are difficult, or impossible, to access
      other than with tools and (b) to collect data on the physical properties of palm
      fruits that are comparable to those available for the nuts cracked open with
      tools by wild chimpanzees. Results showed that the four nut species differ in
      terms of peak-force-at-failure and that peak-force-at-failure is positively
      associated with greater weight (and consequently volume) and apparently with
      structural complexity (i.e. more kernels and thus more partitions); finally for
      three out of four nut species shell thickness is also positively associated with
      greater volume. The finding that the nuts exploited by capuchins with tools have
      very high resistance values support the idea that tool use is indeed mandatory to
      crack them open. Finally, the peak-force-at-failure of the piassava nuts is
      similar to that reported for the very tough panda nuts cracked open by wild
      chimpanzees; this highlights the ecological importance of tool use for exploiting
      high resistance foods in this capuchin species.

PMID- 18618603
TI  - Saponaria officinalis karyology and karyotype by means of image analyzer and
      atomic force microscopy.
AB  - The aim of this work was to offer a contribution to the characterization of
      taxonomic entity of Saponaria officinalis (2n = 28; an herbaceous perennial
      species; saporin, a type 1 Ribosome Inactivating Protein, is present in leaves
      and seeds) by a cytogenetic and karyomorphological approach. We investigated the
      karyotype's morphometry correlated with Stebbin's symmetric index; the same
      information has been used for computing the indices resemblance between
      chromosomes (REC), symmetric indices (SYI), and total form (TF%) which allow the
      comparison between species and evaluation of karyological evolution. Fluorescence
      intensities of the stained nuclei were measured by a flow cytometer and, for the
      first time, values for nuclear DNA content were estimated by comparing nuclei
      fluorescence intensities of the test population with those of appropriate
      internal DNA standards. Our study is also aimed to introduce chromosomal volumes,
      which were determined by atomic force microscopy (AFM), as novel
      karyomorphological parameter which could allow for chromosome discrimination
      especially when tiny ones are present.

PMID- 18618604
TI  - A rationale for the targeted treatment of oligometastases with radiotherapy.
AB  - An oligometastatic state has been proposed wherein patients with metastases
      limited in number and location may benefit from local therapy directed at all
      known sites of metastases. We describe here the clinical and biological basis for
      the oligometastatic state. We present evidence for a potentially curative
      approach to patients with oligometastases using stereotactic body radiotherapy
      (SBRT) and we review the literature for SBRT directed at specific metastatic
      sites in the lungs, liver and multiple organs.

PMID- 18618605
TI  - The analysis of status and clinical implication of KIT and PDGFRA mutations in
      gastrointestinal stromal tumor (GIST).
AB  - BACKGROUND AND OBJECTIVE: To analyze the frequency and spectrum of KIT and
      platelet-derived growth factor receptor-alpha (PDGFRA) gene in a large series of
      study and to explore the clinical implication of mutations in the
      gastrointestinal stromal tumors (GISTs) in China. METHOD: A total of 141 GISTs
      were subject to mutation analysis of KIT (exons 9, 11, 13, and 17) and PDGFRA
      (exons 12 and 18) using PCR amplification and direct sequencing.
      Clinicopathologic characteristics were correlated to gene mutations. RESULTS: Of
      the 141 tumors studied, approximately 76.6% had KIT gene mutations, 2.8% had
      PDGFRA gene mutations and 20.6% had a wild-type gene of KIT and PDGFRA. Among
      those with KIT gene mutations, 70.2% occurred in exon 11, 5.7% in exon 9, 0.7% in
      exon 13, and no mutation was detected in exons 17. The most frequent sites of
      mutation were in exon 11 and the mutations clustered in the classic "hot spot" at
      the 5'end of the exon mostly heterogeneous and the second "hot spot" were
      internal tandem duplications (ITD) at the 3'end of the exon. The overall mutation
      rate was significantly lower in GISTs originated from colorectum or extra
      gastrointestinal tract (chi(2) = 6.728, P = 0.009; chi(2) = 4.059, P = 0.044),
      however, mutation rate on exon 11 was significantly increased in gastric stromal
      tumor (chi(2) = 5.713, P = 0.017; chi(2) = 4.341, P = 0.037). There were no
      significant differences in terms of age, gender, tumor size, mitotic counts,
      grade of malignant potential and liver metastasis in patients with or without
      gene mutations. CONCLUSION: KIT and PDGFRA gene were frequently found in patients
      with GISTs. Gene mutation rate varies in originated organ.

PMID- 18618606
TI  - In hospital outcomes after pancreatectomies: an analysis of a national database
      from 1996 to 2004.
AB  - INTRODUCTION: National complication rates following pancreatectomies have not
      been systematically reported. METHODS: We queried the national hospital discharge
      survey (NHDS) database to analyze risk factors associated with mortality and
      length of stay after pancreatectomies. RESULTS: An estimated 49,346
      pancreatectomies were performed from 1996 to 2004. The national mortality rate is
      9% with an average length of stay 15 days (Interquartile range 10-23) while the
      morbidity is 35%. Size of the hospital (<300 beds) (OR 2.76 (95% CI 1.14-6.70, P
      = 0.02)), post-operative pulmonary edema (OR 2.80 (95% CI 1.28-6.12, P = 0.01))
      and sepsis (OR 5.22 (95% CI 1.94-14.11, P = 0.001)) are associated with higher
      mortality. Patients in larger hospitals (>500 beds) (Rate ratio 0.87 (95% CI 0.83
      0.91, P < 0.001)) had a shorter hospital stay. Temporal trends reveal a shorter
      hospital length of stay in 2004 (Rate ratio 0.86 (95% CI 0.78-0.94, P = 0.001))
      as compared to 1996. The percentage of pancreatectomies performed at larger
      hospitals in 1996 (40%) and 2004 (41%) has remained constant. CONCLUSION: The
      national mortality and morbidity rates after pancreaticoduodenectomy are 9% and
      35%, respectively. Larger hospital size and absence of pulmonary edema and sepsis
      improves mortality. Larger hospitals have better outcomes although the trend for
      regionalization is not apparent.

PMID- 18618607
TI  - Lung cancer A549 cells migrate directionally in DC electric fields with polarized
      and activated EGFRs.
AB  - Endogenous direct-current electric fields (dcEFs) occur in vivo in the form of
      epithelial transcellular potentials or neuronal field potentials. A variety of
      cells respond to dcEFs by migrating directionally, and this is termed
      galvanotaxis. The mechanism by which dcEFs direct cell movement, however, is not
      yet understood, and the effects on lung cancer cells are entirely unknown. We
      demonstrated that cultured human lung adenocarcinoma A549 cells migrate toward
      the cathode in applied dcEFs at 3 V/cm. Fluorescence microscopy showed that both
      epidermal growth factor receptors (EGFRs) and F-actin are polarized to the
      cathode. EGFR inhibitors, cetuximab and AG1478, reduced the migration rate and
      directed motility in dcEFs. Western blots showed that ERK and AKT signaling
      pathways were prominently promoted by dcEFs. EGFR inhibitors could reduce this
      promotion but not completely. These data suggest that polarization of EGFRs and
      the activation of their downstream signals play an important role in the
      galvanotaxis of A549 cells in dcEFs.

PMID- 18618608
TI  - Pyruvate and oxygen consumption throughout the growth and development of murine
      oocytes.
AB  - Growing oocytes in vitro from the most immature stages until they are
      developmentally competent is a major goal of reproductive technology, requiring
      fundamental knowledge of metabolic processes. Carbohydrate metabolism and oxygen
      consumption have been analysed in a series of experiments designed to investigate
      important energy substrates for mouse oocytes and to reveal any qualitative or
      quantitative changes between the primordial and ovulatory follicle stages.
      Primordial follicles were incubated in groups in modified-KSOM medium, whereas
      growing or ovulated oocytes were studied singly and, in both cases, the depletion
      or accumulation of metabolites in spent medium were analysed using
      ultramicrofluorometric assays. The rates of glucose (0.014 +/- 0.006 pmol/hr) and
      pyruvate (0.028 +/- 0.009 pmol/hr) consumption and l-lactate (0.058 +/- 0.023
      pmol/hr) production by primordial follicles suggested that energy production was
      supported by a combination of metabolic pathways, including glycolysis. Pyruvate
      and oxygen consumption per oocyte increased two- and ninefold, respectively,
      between the primary and pre-ovulatory stages (0.82 +/- 0.1 and 1.67 +/- 0.1 pmol
      pyruvate/hr, respectively and 1.4 +/- 0.3 and 7 +/- 0.6 pmol oxygen/hr) after
      which oxygen (12.7 +/- 1.1 pmol/hr) utilisation nearly doubled. Oxygen
      consumption by fully grown oocytes was in excess of oxidation requirements for
      pyruvate. When pyruvate and oxygen consumption rates were normalised for oocyte
      cellular volume, which increased over 130-fold during growth, oocyte metabolism
      was higher in primary follicles than at any subsequent stage, indicating that
      energy needs are greater during a developmental transition. To conclude, pyruvate
      and oxygen were consumed throughout oocyte development at increasing rates. When
      oocyte cellular volume was accounted for, oocytes from primary follicles
      displayed greatest metabolic rates.

PMID- 18618609
TI  - Storage and sorption properties of acetylene in jungle-gym-like open frameworks.
AB  - The acetylene-sorption properties of six porous coordination polymers (PCPs),
      [M(2)(L)(2)(dabco)](n) (dabco=1,4-diazabicyclo[2.2.2]octane, M=Cu(2+) (1), Zn(2+)
      (2), L=1,4-benzenedicarboxylate (bdc; 1 a, 2 a), 1,4-naphthalenedicarboxylate
      (ndc; 1 b, 2 b), 9,10-anthracenedicarboxylate (adc; 1 c, 2 c)), were
      investigated. The acetylene sorption isotherms of 1 and 2 measured at 195 K are
      of type I and show a steep increase at low relative pressures. The sorption
      properties of carbon dioxide at 195 K were also investigated. Compounds 1 and 2
      showed a large difference in onset pressure between acetylene sorption isotherms,
      although the difference between the carbon dioxide sorption isotherms is not so
      significant. In particular, 2 c displayed a remarkable affinity for acetylene.
      The acetylene sorption isotherm at 298 K showed that the adsorption amounts for 2
      c and 2 b at 298 K, 1 atm (101 and 106 mL g(-1), respectively) were higher than
      those of other conventional porous materials. Notably, of the compounds 1 and 2,
      the porous crystals 2 c had the highest affinity for acetylene.

PMID- 18618610
TI  - Ulcerative colitis and adenocarcinoma colon diagnosed simultaneously in an 18
      year-old male with four months history of bloody diarrhea.

PMID- 18618611
TI  - Crosslinking of an oesophagus acellular matrix tissue scaffold.
AB  - The oesophagus acellular matrix (EAM) tissue-scaffold has the potential to serve
      as the foundation for a tissue-engineered oesophagus for repair of ablative
      defects. Similar to all collagen-based biomaterials, the EAM is subject to
      enzymatic degradation in vivo. The introduction of exogenous crosslinks to
      collagen molecules via glutaraldehyde (Glu) is the most accepted method of
      stabilizing collagen biomaterials, but fixation with Glu incurs adverse effects.
      Genipin (Gp), a naturally occurring crosslinking agent, has shown to be effective
      at improving the stability of collagen-based biomaterials with less cytotoxicity
      and reduced in vivo inflammatory responses than Glu. The aim of this study was to
      show that crosslinking with Gp improves the stability of the EAM while
      maintaining minimal biological reactivity and preserving EAM regeneration
      potential in a rat model. EAMs were crosslinked with Gp and Glu. Uncrosslinked
      EAMs served as controls. Denaturation temperature measurement and burst-pressure
      measurement after enzymatic degradation assays were used to determine the
      effectiveness of crosslinking on in vitro stability. Subcutaneous allograft
      implantation and oesophageal epithelial cell-seeding studies assessed the
      crosslinking effects on biological reactivity and regeneration potential,
      respectively. Both Gp and Glu improved EAM stability. After 30 days of
      implantation, the EAM elicited a minimal inflammatory response and crosslinking
      did not increase inflammation. Gp-crosslinked EAMs supported epithelial adhesion
      and proliferation while Glu-crosslinked EAMs did not. Gp improves the stability
      of the EAM while maintaining minimal biological reactivity and preserving EAM
      epithelial proliferation capacity, yielding a tissue scaffold that may form the
      basis of a durable and biocompatible tissue-engineered oesophagus.

PMID- 18618612
TI  - Acidic-basic properties of three alanine-based peptides containing acidic and
      basic side chains: comparison between theory and experiment.
AB  - The purpose of this work was to evaluate the effect of the nature of the
      ionizable end groups, and the solvent, on their acid-base properties in alanine
      based peptides. Hence, the acid-base properties of three alanine-based peptides:
      Ac-KK-(A)(7)-KK-NH(2) (KAK), Ac-OO-(A)(7)-DD-NH(2) (OAD), Ac-KK-(A)(7)-EE-NH(2)
      (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid,
      lysine, and ornithine, respectively, were determined in water and in methanol by
      potentiometry. With the availability of these data, the ability of two
      theoretical methods to simulate pH-metric titration of those peptides was
      assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3
      force field and the Poisson-Boltzmann approach to compute solvation energy
      (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field
      and the Generalized Born model (MD/GB/pH). For OAD and KAE, pK(a1) and pK(a2)
      correspond to the acidic side chains. For all three compounds in both solvents,
      the pK(a1) value is remarkably lower than the pK(a) of a compound modeling the
      respective isolated side chain, which can be explained by the influence of the
      electrostatic field from positively charged ornithine or lysine side chains. The
      experimental titration curves are reproduced well by the MD/GB/pH approach, the
      agreement being better if restraints derived from NMR measurements are
      incorporated in the conformational search. Poorer agreement is achieved by the
      EDMC/PB/pH method.

PMID- 18618613
TI  - Cell therapies: realizing the potential of this new dimension to medical
      therapeutics.
AB  - Stem cells promise to treat conditions poorly served by conventional
      therapeutics. Cells from both embryonic and somatic tissues are being used to
      create cell therapies for genetic, traumatic and degenerative conditions. The
      current human, healthcare and fiscal costs of these conditions are significant.
      This review summarizes the use of stem cells for neurological and cardiac
      disorders and diabetes to determine the requirements for generic translational
      research to assist such therapies to be a reality. While there are multiple
      strategies in each disease area, with no clear favourite, there are clear
      opportunities in treatments that use a single cell type. A key requirement is to
      work with pluripotent progenitor cells to cultivate and differentiate a
      sufficiently large population of functioning cells. Challenges also arise in
      determining and achieving timely delivery of the correct dose of cells to where
      they can most effectively treat the disease and best benefit individual patients.

PMID- 18618615
TI  - Cutaneous soft tissue sarcoma incidence patterns in the U.S. : an analysis of
      12,114 cases.
AB  - BACKGROUND: Cutaneous soft tissue sarcomas (CSTS) are a heterogeneous group of
      mesenchymal neoplasms. To the authors' knowledge, no prior large, population
      based study has focused on CSTS. METHODS: Surveillance, Epidemiology, and End
      Results (SEER) Program incidence and relative survival rates of CSTS were
      analyzed according to race, sex, and histologic type using the 2002 criteria of
      the World Health Organization classification. RESULTS: Among residents of the 13
      SEER registries, 12,114 CSTS were diagnosed from 1992 through 2004. Overall age
      adjusted CSTS incidence rates were highest among blacks (30.8 per 1,000,000
      person-years) followed by whites (25 per 1,000,000 person-years), and American
      Indians/Alaska Natives (11.2 per 1,000,000 person-years) and were lowest among
      Asian/Pacific Islanders (7.7 per 1,000,000 person-years). Kaposi sarcoma (KS)
      accounted for 71.1% of cases, and the rates were similarly ranked.
      Dermatofibrosarcoma protuberans (DFSP) rates also were highest among blacks,
      whereas leiomyosarcoma (LS) and angiosarcoma (AS) rates were highest among
      whites. The rate ratio of men to women was 25.5 for KS, 4.7 for malignant fibrous
      histiocytoma (MFH), 3.7 for LS, 2.0 for AS, and 0.9 for DFSP. The 5-year relative
      survival rates were 99% for patients with DFSP, 89% for patients with MFH, 92%
      for patients with LS, and 45% for patients with AS. KS rates among men in the
      original 9 SEER registries increased more than 30-fold during the 1980s before
      they peaked around 1991 and subsequently declined rapidly because of human
      immunodeficiency virus-associated KS and highly active antiretroviral therapy.
      This KS pattern was evident not only among those ages 20 to 59 years but also
      among those ages 60 to 69 years. From 1978 through 2004, LS and AS rates among
      whites increased exponentially. CONCLUSIONS: CSTS rates varied markedly over time
      and by race, sex, and histologic type, supporting the notion that these
      histologic variants of CSTS areetiologically distinct.

PMID- 18618616
TI  - When electrons meet molecular ions and what happens next: dissociative
      recombination from interstellar molecular clouds to internal combustion engines.
AB  - The interaction of matter with its environment is the driving force behind the
      evolution of 99% of the observed matter in the universe. The majority of the
      visible universe exists in a state of weak ionization, the so called fourth state
      of matter: plasma. Plasmas are ubiquitous, from those occurring naturally;
      interstellar molecular clouds, cometary comae, circumstellar shells, to those
      which are anthropic in origin; flames, combustion engines and fusion reactors.
      The evolution of these plasmas is driven by the interaction of the plasma
      constituents, the ions, and the electrons. One of the most important subsets of
      these reactions is electron-molecular ion recombination. This process is
      significant for two very important reasons. It is an ionization reducing
      reaction, removing two ionised species and producing neutral products.
      Furthermore, these products may themselves be reactive radical species which can
      then further drive the evolution of the plasma. The rate at which the electron
      reacts with the ion depends on many parameters, for examples the collision
      energy, the internal energy of the ion, and the structure of the ion itself.
      Measuring these properties together with the manner in which the system breaks up
      is therefore critical if the evolution of the environment is to be understood at
      all. Several techniques have been developed to study just such reactions to
      obtain the necessary information on the parameters. In this paper the focus will
      be on one the most recently developed of these, the Ion Storage Ring, together
      with the detection tools and techniques used to extract the necessary information
      from the reaction.

PMID- 18618617
TI  - A combination therapy of whole lung lavage and GM-CSF inhalation in pulmonary
      alveolar proteinosis.
AB  - Systemic and inhalation therapy of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) is usually effective in controlling autoimmune pulmonary alveolar
      proteinosis (PAP), but some cases are refractory to GM-CSF therapy and subjected
      to whole lung lavage (WLL). A 9-year-old girl developed severe respiratory
      failure due to autoimmune PAP was treated with inhalational 250 microg of GM-CSF
      daily, however, it was ineffective. Unilateral WLL was performed three times and
      subsequent GM-CSF inhalation therapy yielded marked physiological and
      radiological improvement and was continued for 1 year.

PMID- 18618618
TI  - Effect of bacterial filter on measurement of interrupter resistance in preschool
      and school-aged children.
AB  - BACKGROUND: The interrupter technique is increasingly used in preschool children
      to assess airway resistance (Rint). Use of a bacterial filter is essential for
      prevention of cross-infection in a clinical setting. It is not known how large an
      effect this extra resistance and compliance exert upon interrupter measurements,
      especially on obstructive airways and in smaller children. We aim to determine
      the contribution of the filter to Rint, in a sample of children attending lung
      function testing at an asthma clinic. METHODS: Interrupter measurements were
      performed according to ATS/ERS guidelines during quiet normal breathing at an
      expiratory flow trigger of 200 ml s(-1), with the child seated upright with
      cheeks supported and wearing a nose clip. A minimum of 10 interrupter
      measurements was made with and without a bacterial filter. Spirometric and
      plethysmographic tests were also performed. RESULTS: A small but significant
      difference (0.12 (95% CI 0.06-0.17) kPa s L(-1), P = 0.0002) with 2x SD of 0.34
      kPa s L(-1) was observed between Rint with and without filter in 39 children,
      with a large spread. This difference was not dependent on Rint magnitude, age or
      height, nor on lung function parameters (effective resistance, forced expiratory
      volume in 1 sec, and maximal expiratory flow at 50% of expired vital capacity).
      CONCLUSIONS: A bacterial filter causes a small difference but is not clinically
      significant, with a wide spread comparable to the variability of the technique
      and recommended cut-offs for assessing repeatability and bronchodilation. Age,
      height or severity of obstruction need not be corrected for in general.

PMID- 18618619
TI  - A novel sidestream ultrasonic flow sensor for multiple breath washout in
      children.
AB  - OBJECTIVE: Inert gas multiple breath washout (MBW) for measuring Lung Clearance
      Index using mass spectrometry and 4% sulfur hexafluoride (SF(6)) as the tracer
      gas has been shown to be sensitive for detecting early Cystic Fibrosis (CF) lung
      disease. However, mass spectrometry requires bulky equipment and is expensive to
      buy and maintain. A novel sidestream ultrasonic device may overcome this problem.
      The aims of this study were to assess the feasibility and clinical validity of
      measuring lung volume (functional residual capacity, FRC) and the LCI using the
      sidestream ultrasonic flow sensor in children and adolescents with CF in relation
      to spirometry and plain chest radiographs. PATIENTS AND METHODS: MBW using the
      sidestream ultrasonic device and conventional spirometry were performed in 26
      patients with CF and 22 healthy controls. RESULTS: In the controls (4.7-17.7
      years) LCI was similar to that reported using mass spectrometry (mean (SD) 6.7
      (0.5)). LCI was elevated in 77% of the CF children (6.8-18.9 years), whereas
      spirometry was abnormal in only 38.5%, 61.5%, and 26.9% for FEV(1), MEF(25), and
      FEV(1)/FVC, respectively. This was more marked in children <10 years. LCI
      correlated with the Crispin-Norman score, whereas FEV(1) did not. CONCLUSIONS:
      Sidestream ultrasonic MBW is a valid and simple alternative to mass spectrometry
      for assessing ventilation homogeneity in children.

PMID- 18618620
TI  - Hering-Breuer reflex, lung volume and position in prematurely born infants.
AB  - OBJECTIVES: To investigate the effect of position on the strength of the Hering
      Breuer reflex in prematurely born infants and determine whether any differences
      seen were related to differences in lung or tidal volume between positions.
      WORKING HYPOTHESIS: Position related differences in the strength of the Hering
      Breuer reflex relate to differences in lung or tidal volume. STUDY DESIGN:
      Prospective observational study. PATIENT/SUBJECT SELECTION: Eighteen infants,
      median gestational age 30 (range 25-32) weeks were studied. METHODOLOGY: Infants
      were examined in the supine and prone position, each position was maintained for
      2 hr. At the end of each 2-hr period, the strength of the Hering-Breuer reflex
      was assessed by determining the prolongation of expiration following an end
      inspiratory occlusion. In addition, tidal volume and functional residual capacity
      (FRC) were assessed in each position. RESULTS: The strength of the Hering-Breuer
      reflex was greater (P = 0.01) and the mean FRC was higher (P < 0.0001) in the
      prone compared to the supine position. The position related differences in the
      strength of the reflex correlated significantly with position related differences
      in FRC (P = 0.05). CONCLUSIONS: The Hering-Breuer reflex is stronger in the prone
      compared to the supine position. Our results suggest this is explained by
      position related differences in lung volume.

PMID- 18618622
TI  - Organic cofactors participated more frequently than transition metals in redox
      reactions of primitive proteins.
AB  - Protein redox reactions are one of the most basic and important biochemical
      actions. As amino acids are weak redox mediators, most protein redox functions
      are undertaken by protein cofactors, which include organic ligands and transition
      metal ions. Since both kinds of redox cofactors were available in the pre-protein
      RNA world, it is challenging to explore which one was more involved in redox
      processes of primitive proteins? In this paper, using an examination of the redox
      cofactor usage of putative ancient proteins, we infer that organic ligands
      participated more frequently than transition metals in redox reactions of
      primitive proteins, at least as protein cofactors. This is further supported by
      the relative abundance of amino acids in the primordial world. Supplementary
      material for this article can be found on the BioEssays website.

PMID- 18618621
TI  - SLC6A4 variation and citalopram response.
AB  - The influence of genetic variations in SLC6A4 (serotonin transporter gene) on
      citalopram treatment of depression using the Sequenced Treatment to Relieve
      Depression (STAR*D) sample was assessed. Of primary interest were three
      previously studied polymorphisms: 1) the VNTR variation of the second intron, 2)
      the indel promoter polymorphism (5HTTLPR or SERT), and 3) a single nucleotide
      polymorphism (SNP) rs25531. Additionally, SLC6A4 was resequenced to identify new
      SNPs for exploratory analyses. DNA from 1914 subjects in the STAR*D study were
      genotyped for the intron 2 VNTR region, the indel promoter polymorphism, and
      rs25531. Associations of these variants with remission of depressive symptoms
      were evaluated following citalopram treatment. In white non-Hispanic subjects,
      variations in the intron 2 VNTR (point-wise P = 0.041) and the indel promoter
      polymorphism (point-wise P = 0.039) were associated with remission following
      treatment with citalopram. The haplotype composed of the three candidate loci was
      also associated with remission, with a global p-value of 0.040 and a maximum
      statistic simulation p-value of 0.0031 for the S-a-12 haplotype, under a dominant
      model. One SNP identified through re-sequencing the SLC6A4 gene, Intron7-83-TC,
      showed point-wise evidence of association, which did not remain significant after
      correction for the number of SNPs evaluated in this exploratory analysis. No
      associations between these SLC6A4 variations and remission were found in the
      white Hispanic or black subjects. These findings suggest that multiple variations
      in the SLC6A4 gene are associated with remission in white non-Hispanic depressed
      adults treated with citalopram. The mechanism of action of these variants remains
      to be determined.

PMID- 18618623
TI  - [High-throughput screening for inhibitors of bacterial transglycosylase].

PMID- 18618624
TI  - [Mass spectrometry for detection of biomarkers].

PMID- 18618625
TI  - [What's the individual genome for individual therapy?].

PMID- 18618627
TI  - [The medicinal chemistry of alpha 1 blockers].

PMID- 18618628
TI  - NMR studies of novel Schiff bases derived from L-alpha-amino methyl esters and 3
      hydroxypyridin-4-carboxaldehyde.
AB  - Schiff bases of 3-hydroxypyridin-4-carboxaldehyde and L-alpha-amino esters as
      well as those derived from the structurally related amines lacking the ester
      function have been synthesised. In two cases a tetrahydro-1H-imidazo[4,5
      c]pyridine was formed as a by-product. (1)H, (13)C, (15)N-NMR spectral data and
      density functional theory (DFT) calculations established the structure of all
      compounds.

PMID- 18618629
TI  - Short-term response to adalimumab in childhood inflammatory bowel disease.
AB  - BACKGROUND: Adalimumab is effective for adults with moderate to severe Crohn's
      disease (CD). Data in children with inflammatory bowel disease (IBD) is sparse.
      We aim to evaluate pediatric IBD response to adalimumab. METHODS: We conducted a
      retrospective chart review of pediatric IBD patients treated with adalimumab. We
      defined response as either a decrease in the disease activity index severity or
      remission after 3-6 months of treatment. RESULTS: Ten patients were identified.
      Seven had CD, three had ulcerative colitis (UC). All had colonic disease and
      disease in either the esophagus, stomach, or duodenum. Eight patients initially
      responded to infliximab, 5 with CD and 3 with UC; 2 CD patients had incomplete
      data for evaluation. The mean and median times between initial infliximab and
      initial adalimumab were 29.5 and 24 months, respectively. Eight patients
      responded to adalimumab 40 mg or 80 mg biweekly, or 80 mg initial dose followed
      by 40 mg biweekly. The mean Pediatric Crohn's Disease Activity Index (PCDAI) in
      CD patients before and after adalimumab were 12 and 4.2, respectively (normal
      <or=10). The mean Lichtiger Colitis Activity Index (LCAI) in UC patients before
      and after adalimumab were 9 and 5.1, respectively (normal <10). Corticosteroids
      were weaned off in 4/7 patients at 1 to 10 months after initiation of adalimumab.
      One patient with CD and 1 patient with UC failed adalimumab, required surgery,
      and remained on corticosteroids. CONCLUSIONS: Adalimumab is useful in pediatric
      IBD patients who become intolerant of infliximab.

PMID- 18618630
TI  - Effects of fistula on healthcare costs and utilization for patients with Crohn's
      disease treated in a managed care environment.
AB  - BACKGROUND: Fistulas are a common complication of Crohn's disease (CD) and are
      difficult to treat effectively. This study aimed to assess the effects of fistula
      on annual costs of healthcare and resource utilization for patients with CD.
      METHODS: A retrospective analysis, using the PharMetrics database, of patients
      with a diagnosis of CD from January 1, 2000 through June 30, 2005 was conducted.
      Using paid claim amounts, healthcare costs and resource utilization were compared
      for patients with and without fistula in the year following diagnosis. Further
      analysis compared costs for adult, pediatric, and older adult patients with and
      without fistula. RESULTS: This analysis included 13,454 patients with CD, of whom
      12,683 (94.3%) had no diagnosis of fistula. The total median (range) cost per
      patient was higher for the fistula cohort ($10,863 [$0-$1,307,019]) than the
      nonfistula cohort ($6268 [$0-$1,181,485]), driven mainly by higher hospital and
      surgery costs. Median healthcare costs and resource utilization rates were
      generally higher for patients with fistula compared with those without fistula in
      all 3 age groups, with some of the largest differences observed in the pediatric
      cohort. CONCLUSIONS: Fistulas are often a difficult and costly complication of
      CD. This study determined that patients with fistulizing CD have higher
      healthcare costs and resource consumption than patients without fistula. Use of
      therapies that heal fistulas may help deter some of the high costs and intensive
      resource utilization found in this study. Economic analyses need to account for
      these issues when assessing the cost-effectiveness of therapies targeting
      fistulizing disease.

PMID- 18618632
TI  - [Benign prostatic hypertrophy and the benign prostatic syndrome].

PMID- 18618633
TI  - Tetomilast suppressed production of proinflammatory cytokines from human
      monocytes and ameliorated chronic colitis in IL-10-deficient mice.
AB  - BACKGROUND: Tetomilast (OPC-6535) was originally developed as a compound
      inhibiting superoxide production in neutrophils. Although its mechanism of action
      is not completely understood, phosphodiesterase type 4 inhibitory function has
      been postulated. The therapeutic effect of PDE4 inhibitors has been reported for
      chronic inflammatory disorders such as chronic obstructive pulmonary diseases. In
      this study we aimed to examine whether tetomilast could be a novel drug for
      inflammatory bowel diseases by further clarifying its antiinflammatory effects.
      METHODS: Cytokines from human peripheral blood mononuclear cells were measured by
      enzyme-linked immunosorbent assay (ELISA) and Cytokine Beads Array. The
      transcripts were quantified by reverse-transcriptase polymerase chain reaction
      (RT-PCR). Phosphorylation of transcription factors was examined by phosflow. To
      examine its in vivo effect, a once-daily oral dose of tetomilast was tested in
      murine IL-10(-/-) chronic colitis. RESULTS: Tetomilast suppressed TNF-alpha and
      IL-12 but not IL-10 production from lipopolysaccharide (LPS)-stimulated human
      monocytes. It suppressed TNF-alpha, IFN-gamma, and IL-10 from CD4 lymphocytes.
      Tetomilast suppressed cytokine production at the transcriptional level but did
      not alter phosphorylation of p65, ERK, p38, and STAT3. HT-89, a protein kinase A
      inhibitor, did not abolish the effect of tetomilast, suggesting that it was
      independent from the classical cAMP/PKA pathway. IL-10 was not essential to the
      inhibitory effect of tetomilast on TNF-alpha and IL-12. Tetomilast ameliorated IL
      10(-/-) chronic colitis with reduced clinical symptoms, serum amyloid A, and
      histological scores with decreased TNF-alpha mRNA expression. CONCLUSIONS:
      Tetomilast exerts its antiinflammatory effects on human monocytes and CD4 cells.
      Combined with in vivo data these findings support the feasibility of tetomilast
      as a novel drug for inflammatory bowel diseases.

PMID- 18618634
TI  - Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic
      responses in inflammatory bowel disease?
AB  - BACKGROUND: Smoking differentially influences susceptibility to the inflammatory
      bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC). We
      investigated the effects of nicotine on cytokine, cell cycle, and apoptotic
      responses in peripheral blood mononuclear cells (PBMCs) from IBD patients and
      healthy controls (HCs). METHODS: PBMCs from IBD patients and HC were stimulated
      with lipopolysaccharide (LPS; 1 microg/mL) or phytohemagglutinin (PHA, 5 or 0.5
      microg/mL), +/- nicotine (1, 10, 100 microg/mL). Cytokines (IL1beta, IL2, IL10,
      IL12/IL23p40, TGFbeta, TNFalpha) were measured in supernatants at 24 hours. After
      72 hours cells were analyzed by flow cytometry for cell cycle and apoptosis.
      Statistical modeling was used to identify interactions between cytokines and cell
      cycle / apoptosis and minimize confounding effects. RESULTS: Stimulation by LPS
      and PHA (5 microg/mL) increased IL12/IL23p40 production from CD and UC versus HC
      (P < 0.05); PHA (0.5 microg/mL) increased IL1beta in UC and decreased TGFbeta
      from CD and UC (P < 0.01). In all groups, nicotine reduced LPS- and PHA (0.5
      microg/mL)-stimulated production of IL1beta, IL10, TGFbeta, and TNFalpha (P <
      0.001). Cell cycle analysis showed that PHA, but not LPS, induced proliferation
      and decreased G(0)/G(1) resting cells in CD and UC versus HC (P < 0.001).
      Nicotine decreased PHA-stimulated S-phase proliferation and increased G(0)/G(1)
      resting cells (P < 0.01). Modeling showed independent associations between
      IL12/IL23p40 and apoptosis (P = 0.01), IL1beta and resting cells (P = 0.006),
      TNFalpha and proliferating cells (P < 0.001). Disease activity and smoking habit
      had no effect. CONCLUSIONS: Dysregulated cytokine profiles in UC and CD are
      associated with specific alterations in cell cycle responses; these effects may
      be modified by nicotine, and potentially by anticytokine therapies.

PMID- 18618635
TI  - Structural determination of flavonoids from Sophora flavescens.
AB  - Eight flavonoids were isolated from Sophora flavescens. Among them, three
      prenylflavanones: (2S)-6[2(3-hydroxyisopropyl)-5-methyl-4-hexenyl]-5-methoxy
      7,2', 4'-trihydroxyflavanone (1), (2S)-5, 4'-dimethoxy-8-lavandulyl-7, 2'
      dihydroxy flavanone (2) and (2S)-8-(5-hydroxy-2-isopropenyl-5-methylhexyl)-7
      methoxy-5,2', 4'-trihydroxyflavanone (3) are new compounds. Their chemical
      structures were determined by spectral methods including 2D NMR.

PMID- 18618636
TI  - Two distinct groups of colorectal cancer in inflammatory bowel disease.
AB  - BACKGROUND: The histological variability in colitis-associated colorectal cancer
      (CRC in inflammatory bowel disease [IBD]) and the association to clinical factors
      is unknown. METHODS: In population-based material including 67 patients with CRC
      in IBD, histopathology of the cancers and tissue samples from different
      colorectal localizations were reevaluated, and relationships to clinical factors
      analyzed. RESULTS: Forty-three of 60 patients (75%) showed dysplasia in the
      colorectum apart from the cancer, while 17 (25%) had no dysplasia at cancer
      diagnosis. Mean age at onset of IBD was 22 years in patients with and 34 years in
      patients without dysplasia (P = 0.01). The mean duration of colitis-CRC interval
      was 21 years in patients with and 16 years in patients without dysplasia (P =
      0.02). The latter group included all patients with a colitis-CRC interval <10
      years. Active inflammation was more likely to occur in patients with dysplasia
      (odds ratio [OR] 4.2). The 2 groups were not discriminated by gender, family
      history of CRC or IBD, diagnosis of PSC, medical treatment, active symptoms, or
      histological features like type of cancer and differentiation. In multiple
      logistic regression analysis the age at onset of IBD was the strongest predictive
      variable for dysplasia at cancer diagnosis (P = 0.025). CONCLUSIONS: Widespread
      neoplasia occurs in the majority of cases with CRC in IBD and is associated with
      early onset of IBD. Localized neoplasia occurs in about a quarter of the patients
      and shows an association with late-onset IBD. The 2 groups probably represent
      different pathogenetic entities of neoplasia in IBD. This might have consequences
      for surveillance strategies.

PMID- 18618638
TI  - Multirate state and parameter estimation in an antibiotic fermentation with
      delayed measurements.
AB  - This article discusses issues related to estimation and monitoring of
      fermentation processes that exhibit endogenous metabolism and time-varying
      maintenance activity. Such culture-related activities hamper the use of
      traditional, software sensor-based algorithms, such as the extended kalman filter
      (EKF). In the approach presented here, the individual effects of the endogenous
      decay and the true maintenance processes have been lumped to represent a modified
      maintenance coefficient, m(c). Model equations that relate measurable process
      outputs, such as the carbon dioxide evolution rate (CER) and biomass, to the
      observable process parameters (such as net specific growth rate and the modified
      maintenance coefficient) are proposed. These model equations are used in an
      estimator that can formally accommodate delayed, infrequent measurements of the
      culture states (such as the biomass) as well as frequent, culture-related
      secondary measurements (such as the CER). The resulting multirate software sensor
      based estimation strategy is used to monitor biomass profiles as well as profiles
      of critical fermentation parameters, such as the specific growth for a fed-batch
      fermentation of Streptomyces clavuligerus.

PMID- 18618639
TI  - The existence of a biological equilibrium in a trickling filter for waste gas
      purification.
AB  - Clogging is well-known phenomenon in the application of a biological tricking
      filter for both waste gas and wastewater treatment. Nevertheless, no such
      observations or even significant changes in pressure drop have ever been recorded
      during the long-term processing of a waste gas containing dichloromethane (DCM)
      as a sole carbon source. To obtain more information about this phenomenon, a
      detailed investigation into the carbon balance of this system has been performed.
      During a period of operation of about 200 days the rate of DCM elimination and
      the overall rate of CO(2) production in a continuously operating filter were
      therefore recorded daily, thus allowing an evaluation of the overall conversion
      process. Furthermore pseudo-steady-state measurements were carried out on a
      regular basis. These experiments reveal more detailed information on the actual
      DCM conversion by Hyphomicrobium GJ21 within the biofilm. The combined results of
      the experiments described in this article show that on an overall basis a so
      called biological equilibrium, i.e., a situation of no net biomass accumulation,
      is obtained in the course of time. It appeared that the overall rate of CO(2)
      production slowly increased until, after some 200 days, it finally counter
      balanced the conversion rate of DCM on a molar-basis. As opposed to this result,
      all pseudo-steady-state experiments indicated that about 60% of the eliminated
      primary carbon source is converted into biomass. This is in good agreements with
      results from microkinetic experiments. Based on these results and evaluation of
      the experimental data, it is concluded that interactions between several
      microbial populations are involved in this biological equilibrium. These
      interactions include both biomass growth and biomass degradation.

PMID- 18618640
TI  - Evaluation of D-amino acid oxidase from Rhodotorula gracilis for the production
      of alpha-keto acids: a reactor system.
AB  - The study reports on the development of a bioreactor for the production of alpha
      keto acids from D,L- or D-amino acids using Rhodotorula gracilis D-amino acid
      oxidase. D-amino acid oxidase was co-immobilized with catalase on Affi-Gel 10
      matrix, and the reactor was operated as a continuous-stirred tank reactor (CSTR)
      or stirred tank with medium recycling conditions. The optimum substrate
      concentration and quantity of biocatalyst were determined (5 mM and 1.2 mg/L,
      respectively). Under optimum operating conditions, product formation was linearly
      related to both substrate and enzyme concentration, showing the system to be
      highly flexible. Under these conditions, in a stirred tank, over 90% conversion
      was achieved in 30 min with a maximum production of 0.23 g of pyruvic
      acid/day/enzyme units. Product was recovered by ion exchange chromatography. The
      operational stability of the reactor was high (up to 9.5 h of operation without
      loss of activity) and the inactivation half-life was not reached even after 18 h
      or 36 bioconversion cycles. This represents the first case of a reactor developed
      successfully with a D-amino acid oxidase.

PMID- 18618641
TI  - Purification and processing of cellulose-binding domain-alkaline phosphatase
      fusion proteins.
AB  - Fusion of the leader peptide and the cellulose-binding domain (CBD) of
      endoglucanase A (CenA) from Cellulomonas fimi, with of without linker sequences,
      to the N-terminus of alkaline phosphatase (PhoA) from Escherichia coli leads to
      the accumulation of significant amounts of the CBD-PhoA fusion proteins in the
      supernatants of E. coli cultures. The fusion proteins can be purified from the
      supernatants by affinity chromatography on cellulose. The fusion protein can be
      desorbed from the cellulose with water or guanidine-HCl. If the sequence IEGR in
      present between the CBD and PhoA, the CBD can be cleaved from the PhoA with
      factor Xa. The efficiency of hydrolysis by factor Xa is strongly in fluenced by
      the amino acids on either side of the IEGR sequence. The CBD released by factor
      Xa is removed by adsorption to cellulose. A nonspecific proteases from C. fimi,
      which hydrolyzes native CenA between the CBD and the catalytic domain, may be
      useful for removing the CBD from some fusion proteins.

PMID- 18618642
TI  - Effect of alcohol feeding mode on the biosynthesis of poly (3-hydroxybutyrate-co
      3-hyroxyvalerate).
AB  - An alcohol utilizing Alcaligenes eutrophus produced poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) copolymer under phosphate limitation. Fermentation was
      performed for 42-46 h in a computer-controlled 5-L working volume fed-batch
      fermentor using ethanol and propanol as carbon sources. The culture experienced
      phosphate limitation in approximately 19 h. When propanol was used as a sole
      carbon source, 24 g/L of copolymer with 36.5 mol % of hydroxyvalerate (HV) was
      produced at a polymer yield of 0.41 g polymer/g alcohol (g/g) and an average
      polymer production rate of 0.08 g polymer/g residual biomass-h (g/g-h). Two
      experiments switching alcohol after phosphate exhaustion resulted in better
      polymer production (g/L), polymer yield (g/g) on alcohol, HV yield (g/g) on
      propanol, and average polymer production rate (g/g-h) as compared to propanol run
      without alcohol switching. One switching experiment was from a mixture of 50%
      ethanol and 50% propanol to 100% propanol and the other experiment was from 100%
      ethanol to a mixture of 65% ethanol and 35% propanol. Polymer yield for these two
      experiments was 0.51 g/g and 0.46 g/g, respectively. However, HV mol % in the
      copolymer for these two runs (30.8 mol % 12.6 mol % respectively) was lower
      compared to propanol run without alcohol switching (3605 mol %). Direct switch
      from ethanol to propanol did not support cell growth and polymer production.
      Polymer production rate and polymer yield changed with time, and the pattern was
      dependent upon the alcohol feeding mode.

PMID- 18618643
TI  - Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer
      reactor.
AB  - The titanium static mixer reactor, demonstrated for a variety of vaccine
      processes during the late 197s, was investigated for the production of attenuated
      hepatitis A virus antigen from anchorage-dependent MRC-5 cells. This reactor
      system used Charles River Biotechnological Services cabinets for monitoring and
      process control. Cell inoculation protocols, using 6000-10,000 cells/cm(2),
      resulted on over 95% attachment at both the laboratory and pilot scales. Indirect
      monitoring techniques using oxygen, glucose, L-serine, and L-glutamine uptake
      rates were indicative of cell growth prior to virus inoculation as well as
      environmental and/or nutrient limitations. Seven laboratory-scale (3900 cm(2))
      runs and one pilotscale (265,000 cm(2)) run were conducted to investigate
      refeeding regiments, parallel versus perpendicular element orientation, increased
      element surface area per unit volume, and scale-up performance. In general,
      lysate antigen yields achieved were similar to those of parallel T-flasks
      cultivated under similar conditions.

PMID- 18618644
TI  - Characterization of a prototype industrial on-line analyzer for
      bicarbonate/carbonate monitoring.
AB  - In many biological reactors bicarbonate is the major species determining pH
      buffering capacity, or alkalinity. In anaerobic digesters bicarbonate levels
      should be within 10 to 50 mM for stable operation. Bicarbonate alkalinity in
      wastewater treatment processes in routinely measured off-line titrimetrically.
      Recently we have described the principle of a novel on-line method of measuring
      bicarbonate alkalinity. In the prototype device described here, a continuous
      stream (15 cm(3) min(-1)) of the substrate to be monitored was saturated with
      gaseous CO2, acidified by the addition of excess acid, and the rate of carbon
      dioxide evolution, proportional to the concentration of bicarbonate/carbonate in
      the liquid flow, continuously measured by a sensitive gas meter. The instrument
      was robust and its response was satisfactory for wastewater treatment process
      control applications, with linearity in the range 5 to 50 mM HCO3(-), a response
      time in the order of 30 min, and accuracy of the order of 7% in the concentration
      range 5 to 50 mM sodium bicarbonate. The device was not affected by interference
      from volatile fatty acids, does not make use of pH probes which in many wastes
      are subject to fouling, and may form the basis of a digester control strategy.

PMID- 18618645
TI  - Antibiotic production by Streptomyces aureofaciens using self-cycling
      fermentation.
AB  - The self-cycling frementation (;rSCF) technique was applied to culture of
      Streptomyces aureofaciens. SCF is a method of continuous fermentation in which
      the metabolism of a microorganism is monitored by a measurement such as dissolved
      oxygen. These data are sent to a computer to allow it to control the system.
      Tetracycline production was observed only at exceedingly low iron concentrations
      in the growth medium. Repeatability of cycles was found to be dependent upon the
      presence of tetracycline in the fermentation broth as well as the strain of
      microorganism grown in the fermentor. Tetracycline was produced by an improved
      specific rate when compared to results in the literature for this organism grown
      using the batch method.

PMID- 18618646
TI  - Comparison of recombinant Escherichia coli strains for synthesis and accumulation
      of poly-(3-hydroxybutyric acid) and morphological changes.
AB  - A stable high-copy-number plasmid pSYL105 containing the Alcaligenes eutrophus
      polyhydroxyalkanoic acid (PHA) biosynthesis genes was constructed. This plasmid
      was transferred to seven Escherichia coli strains (K12, B, W, XL1-Blue, JM109,
      DH5alpha, and HB101), which were subsequently compared for their ability to
      synthesize and accumulate ploy- (3-hydroxybutyric acid) (PHB). Growth of
      recombinant cells and PHB synthesis were investigated in detail in Luria-Bertani
      (LB) medium containing 20 g/L glucose. Cell growth, the rate of PHB synthesis,
      the extent of PHB accumulation, the amount of glucose utilized, and the amount of
      acetate formed varied from one strain to another. XL1-Blue (pSYL105) and B
      (pSYL105) synthesized PHB at the fastest rate, which was ca. 0.2 g PHB/g true
      cell mass-h, and produced PHB up to 6-7 g/L. The yields of cell mass, true cell
      mass, and PHB varied considerably among the strains. The PHB yield of XL1-Blue
      (pSYL105) in LB plus 20 g/L glucose was as high as 0.369 g PHB/g glucose. Strains
      W (pSYL105) and K12 (pSYL105) accumulated the least amount of PHB with the lowest
      PHB yield at the lowest synthesis rate. JM109 (pSYL105) accumulated PHB to the
      highest extent (85.6%) with relatively low true cell mass (0.77 g/L).
      Considerable filamentation of cells accumulating PHB was observed for all strains
      except for K12 and W, which seemed to be due either to the overexpression of the
      foreign PHA biosynthesis enzymes or to the accumulation of PHB.

PMID- 18618647
TI  - An Escherichia coli plasmid vector system for production of streptavidin fusion
      proteins: expression and bioselective adsorption of streptavidin-beta
      galactosidase.
AB  - Covalently immobilized biotin was used as a biospecific adsorbant to investigate
      the application of streptavidin as an affinity domain for simultaneous
      purification and immobilization of recombinant proteins. A streptavidin-beta
      galactosidase fusion protein was constructed and tested as a model system. The
      gene for streptavidin from Streptomyces avidinii was modified by polymerase chain
      reaction to mutate the stop codon and to facilitate cloning into an Escherichia
      coli expression vector yielding a versatile plasmid with 37 unique restriction
      enzyme sites at the 3' end. E. coli beta-galactosidase was cloned in-frame to the
      streptavidin gene. Analysis of lysates of induced recombinant E. coli cells by
      SDS-PAGE and Western blots indicated that the 133.6-kDa fusion protein was
      expressed. Sulfosuccinimidyl-6-(biotinamido) hexanoate was covalently immobilized
      on 3-aminopropyl-controled-pore glass beads. Exposure of recombinant cell lysates
      to this support indicated that streptavidin-beta-galactosidase was bioselectively
      adsorbed. The resulting biocatalyst contained 300 mg protein per gram of beads
      and exhibited a specific activity of 306 betamol/min per milligram protein with o
      nitrophenyl-beta-D-galactopyranoside as substrate corresponding to approximately
      50% of that observed for commercially pure E. coli beta-galactosidase.

PMID- 18618648
TI  - Immiscible organic solvent inactivation of urease, chymotrypsin, lipase, and
      ribonuclease: separation of dissolved solvent and interfacial effects.
AB  - A new technique with controlled interface generation allows separation and
      quantitation of enzyme inactivation by both solvent/aqueous interface and
      dissolved solvent. This has now been used in n-butanol, isopropylether, 2
      octanone, n-hexane, n-butylbenzene, and n-tridecane. Ribonuclease was stable with
      all the solvent/aqueous interfaces studied. Chymotrypsin was mainly inactivated
      by the more hydrophobic solvent/aqueous interfaces, whereas lipase was only
      inactivated by the less hydrophobic solvent/aqueous interfaces. Urease was
      inactivated by some interfaces, but not all, without an obvious trend. Thus, the
      commonly expected simple relationship with solvent polarity (e.g., log P) does
      not apply when interfacial inactivation is determined specifically. Greater
      dissolved solvent inactivation occurred with the more polar solvents, though only
      a general trend was apparent with log P. A better correlation was noted with the
      Hilde-brand solubility parameter. Interfacial effects are discussed with
      reference to enzyme molecular weight, denaturation temperature, hydrophobicity,
      and adiabatic compressibility.

PMID- 18618649
TI  - The use of hollow fiber cross-flow microfiltration in bioaccumulation and
      continuous removal of heavy metals from solution by Saccharomyces cerevisiae.
AB  - Cross-flow microfiltration was shown to retain Saccharomyces cerevisiae biomass
      utilized for heavy metal bioaccumulation. The passage of metal-laden influent
      through a series of sequential bioaccumulation systems allowed for further
      reductions in the levels of copper, cadmium, and cobalt in the final effluent
      than that afforded by a single bioaccumulation process. Serial bioaccumulation
      systems also allowed for partial separation of metals from dual metal influents.
      More than one elemental metal cation could be accumulated simultaneously and in
      greater quantities than when a single metal was present in the effluent (Cu(2+)
      0.43 mmol, Cu(2+) + Cd(2+) 0.67 mmol, and Cu(2+) + Co(2+) 0.83 mmol/g yeast dry
      mass when the initial concentration of each of the metal species was 0.2 mmol x
      L(-1)). Co-accumulation of two different metal cations allowed higher total
      levels of bioaccumulation than found with a single metal. The flux rate was 2.9 x
      10(2) L x h(-2)microm(-2) using a polypropylene microfiltration membrane (0.1
      microm pore size) at 25 degrees C.

PMID- 18618650
TI  - Effect of Vitreoscilla hemoglobin expression on growth and specific tissue
      plasminogen activator productivity in recombinant chinese hamster ovary cells.
AB  - Previous studies suggest that secretion of cloned proteins synthesized by
      recombinant Chinese hamster ovary (CHO) cells can be adenosine triphosphate (ATP)
      limited. Other research indicates that the presence of cloned Vitreoscilla
      hemoglobin (VHb) enhances ATP production in oxygen-limited Escherichia coli. To
      evaluate the influence of VHb expression on recombinant CHO cell productivity,
      the vhb gene has been fused to the mouse mammary tumor virus (MMTV) promoter and
      cloned in a CHO cell line previously engineered to express human tissue
      plasminogen activator (tPA). Western blot analysis confirms dexamethasone
      inducible VHb expression in all of the clones tested. Batch cultivation
      experiments with one VHb-expressing clone and the parental CHO-tPA expressing
      cells. The VHb-expressing clone exhibits specific tPA production 40 to 100%
      greater than the parental CHO-tPA culture.

PMID- 18618651
TI  - An uncommon cause of a vascular mass in the left lung in neonate: a case report
      with a brief review of literature.
AB  - A 20-day-old female child presented with mild respiratory distress since first
      week of life. On examination there was an ejection systolic murmur at left
      sternal border. Chest x-ray revealed well-defined mass in the left lung.
      Echocardiogram showed features suggestive tetrology of fallot with absent
      pulmonary valve with massively dilated main and left pulmonary artery. We report
      a rare cause of vascular mass in a neonate due to tetrology fallot with absent
      pulmonary valve.

PMID- 18618652
TI  - Acute respiratory distress syndrome by cytomegalovirus infection in an
      immunocompetent infant.
AB  - A 2-month-old female infant was admitted with progressive respiratory distress,
      fever, and diagnosed with acute respiratory distress syndrome (ARDS). The primary
      pulmonary pathogen was proven to be cytomegalovirus (CMV) from bronchoalveolar
      lavage fluid, urine, and blood specimens. Other immunologic findings were normal.
      CMV-induced ARDS has not been reported previously in immunocompetent infants.

PMID- 18618653
TI  - Methylprednisolone inhibits the expression of glial fibrillary acidic protein and
      chondroitin sulfate proteoglycans in reactivated astrocytes.
AB  - Reactive gliosis caused by post-traumatic injury often results in marked
      expression of chondroitin sulfate proteoglycan (CSPG), which inhibits neurite
      outgrowth and regeneration. Methylprednisolone (MP), a synthetic glucocorticoid,
      has been shown to have neuroprotective and anti-inflammatory effects for the
      treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG
      expression in reactive glial cells remains unclear. In our study, we induced
      astrocyte reactivation using alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA) and cyclothiazide to mimic the excitotoxic stimuli of SCI. The
      expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte
      reactivation, and CSPG neurocan and phosphacan were significantly elevated by
      AMPA treatment. The conditioned media from AMPA-treated astrocytes strongly
      inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect
      was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG
      expression in adult rats with SCI. Additionally, both the glucocorticoid receptor
      (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP
      and neurocan expression. Taken together, these results suggest that MP may
      improve neuronal repair and promote neurite outgrowth after excitotoxic insult
      via GR-mediated downregulation of astrocyte reactivation and inhibition of CSPG
      expression.

PMID- 18618655
TI  - Mass spectrometry-based proteomics in reproductive medicine.
AB  - The emergence of powerful mass spectrometry-based proteomic techniques has added
      a new dimension to the field of biomedical research. Application of these high
      throughput methodologies in pregnancy-related pathology has contributed to the
      comprehension of the underlying pathophysiologies and the successful
      identification of relevant protein biomarkers that can potentially change early
      diagnosis and treatment of several medical conditions related to human pregnancy.
      Most of the existing research on human reproduction and gestation has focused on
      follicular fluid, cervical/vaginal fluid, and amniotic fluid. Although proteome
      technologies in reproductive medicine research are not as yet widely applied,
      characterization of the proteome of reproductive fluids can be expected to
      significantly improve maternal healthcare. This article aims to summarize the
      applications of mass spectrometry based technology on the most important and
      specific biological fluids related to reproduction and gestation.

PMID- 18618654
TI  - CPEB1 regulates beta-catenin mRNA translation and cell migration in astrocytes.
AB  - A crucial step in directed cell migration is the recruitment of cytoskeletal
      regulatory and signaling proteins to the leading edge of the cell. One protein
      localized to the leading edge of a migrating astrocyte is beta-catenin. Using an
      in vitro wound-healing assay, we show that the localization of beta-catenin to
      the leading edge is dependent upon new protein synthesis at the time of wounding.
      We examined the mRNA encoding beta-catenin for potential regulatory elements and
      identified a conserved cytoplasmic polyadenylation element in the 3'-untranslated
      region (UTR). We now show that the CPE-binding protein (CPEB1) is expressed in
      astrocytes and that translation of beta-catenin mRNA is regulated by CPEB1.
      Further, expression of a mutant CPEB1 protein in astrocytes not only blocks beta
      catenin protein localization, it also inhibits cell migration. These findings
      demonstrate a role for CPEB1-mediated protein synthesis in the localization of
      beta-catenin protein to the leading edge of migrating astrocytes and in
      regulating directed cell motility.

PMID- 18618656
TI  - Plant proteomics: concepts, applications, and novel strategies for data
      interpretation.
AB  - Proteomics is an essential source of information about biological systems because
      it generates knowledge about the concentrations, interactions, functions, and
      catalytic activities of proteins, which are the major structural and functional
      determinants of cells. In the last few years significant technology development
      has taken place both at the level of data analysis software and mass spectrometry
      hardware. Conceptual progress in proteomics has made possible the analysis of
      entire proteomes at previously unprecedented density and accuracy. New concepts
      have emerged that comprise quantitative analyses of full proteomes, database
      independent protein identification strategies, targeted quantitative proteomics
      approaches with proteotypic peptides and the systematic analysis of an increasing
      number of posttranslational modifications at high temporal and spatial
      resolution. Although plant proteomics is making progress, there are still several
      analytical challenges that await experimental and conceptual solutions. With this
      review I will highlight the current status of plant proteomics and put it into
      the context of the aforementioned conceptual progress in the field, illustrate
      some of the plant-specific challenges and present my view on the great
      opportunities for plant systems biology offered by proteomics.

PMID- 18618657
TI  - An ancient DNA test of a founder effect in Native American ABO blood group
      frequencies.
AB  - Anthropologists have assumed that reduced genetic diversity in extant Native
      Americans is due to a founder effect that occurred during the initial peopling of
      the Americas. However, low diversity could also be the result of subsequent
      historical events, such as the population decline following European contact. In
      this study, we show that autosomal DNA from ancient Native American skeletal
      remains can be used to investigate the low level of ABO blood group diversity in
      the Americas. Extant Native Americans exhibit a high frequency of blood type O,
      which may reflect a founder effect, genetic drift associated with the historical
      population decline, or natural selection in response to the smallpox epidemics
      that occurred following European contact. To help distinguish between these
      possibilities, we determined the ABO genotypes of 15 precontact individuals from
      eastern North America. The precontact ABO frequencies were not significantly
      different from those observed in extant Native Americans from the same region,
      but they did differ significantly from the ABO frequencies in extant Siberian
      populations. Studies of other precontact populations are needed to better test
      the three hypotheses for low ABO blood group diversity in the Americas, but our
      findings are most consistent with the hypothesis of a founder effect during the
      initial settlement of this continent.

PMID- 18618658
TI  - Y-chromosome variation among Sudanese: restricted gene flow, concordance with
      language, geography, and history.
AB  - We study the major levels of Y-chromosome haplogroup variation in 15 Sudanese
      populations by typing major Y-haplogroups in 445 unrelated males representing the
      three linguistic families in Sudan. Our analysis shows Sudanese populations fall
      into haplogroups A, B, E, F, I, J, K, and R in frequencies of 16.9, 7.9, 34.4,
      3.1, 1.3, 22.5, 0.9, and 13% respectively. Haplogroups A, B, and E occur mainly
      in Nilo-Saharan speaking groups including Nilotics, Fur, Borgu, and Masalit;
      whereas haplogroups F, I, J, K, and R are more frequent among Afro-Asiatic
      speaking groups including Arabs, Beja, Copts, and Hausa, and Niger-Congo speakers
      from the Fulani ethnic group. Mantel tests reveal a strong correlation between
      genetic and linguistic structures (r = 0.31, P = 0.007), and a similar
      correlation between genetic and geographic distances (r = 0.29, P = 0.025) that
      appears after removing nomadic pastoralists of no known geographic locality from
      the analysis. The bulk of genetic diversity appears to be a consequence of recent
      migrations and demographic events mainly from Asia and Europe, evident in a
      higher migration rate for speakers of Afro-Asiatic as compared with the Nilo
      Saharan family of languages, and a generally higher effective population size for
      the former. The data provide insights not only into the history of the Nile
      Valley, but also in part to the history of Africa and the area of the Sahel.

PMID- 18618659
TI  - Differential NMDA-dependent activation of glial cells in mouse hippocampus.
AB  - In the hippocampus, the NMDA receptor is thought to be an important glutamate
      receptor involved in synaptic plasticity and in memory processes. Until recently,
      NMDA receptors have been considered solely as neuronal components, but some
      evidence suggests that glial cells in the hippocampus, and in particular
      astrocytes, also could be activated by NMDA applications. On the basis of their
      shape and electrophysiological properties (linear and rectified I/V curve), we
      describe two different populations of glial cells from GFAP-GFP transgenic mice
      that are activated differentially by NMDA. We found that linear glial cells were
      depolarized by NMDA that was not dependent on Ca2+ rise but partially involved a
      Ca2+ entry. Additionally, NMDA-induced depolarization of linear glial cells
      involved both a TTX-independent pathway likely through a direct activation, and a
      TTX-dependent pathway that required neuronal activity. The NMDA-induced
      depolarization in these cells was in part due to the activation of glutamate
      transporters and GABA B receptors. Furthermore, TTX-dependent NMDA-induced
      activation regulates the level of gap junction coupling between linear glial
      cells. In contrast, NMDA-induced depolarization in outward rectifying cells do
      not require a Ca2+ rise but are mediated directly by Ca2+ entry and are
      independent of glutamate transporters, GABA B and GABA A receptors. Our findings
      reveal that NMDA differentially activates hippocampal glial cells and the glial
      network through heterogeneous mechanisms in a cell-type specific manner.

PMID- 18618660
TI  - Suicidal and death ideation in Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic, disabling illness affecting primarily the
      elderly and is associated with a high prevalence of depression. Although these
      are known risk factors for suicidal and death ideation, little is known about the
      prevalence and correlates of such ideation in PD. A convenience sample of 116
      outpatients with idiopathic PD at two movement disorders centers were
      administered a modified Paykel Scale for suicidal and death ideation, as well as
      an extensive psychiatric, neuropsychological, and neurological battery.
      Univariate and multivariate logistic regression models were used to determine the
      correlates of suicidal or death ideation. Current death ideation (28%) or suicide
      ideation (11%) were present in 30% of the sample, and 4% had a lifetime suicide
      attempt. On univariate logistic regression analysis, increasing severity of
      depression (odds ratio = 2.92, 95% CI 2.01-4.24, P < 0.001), impulse control
      disorder (ICD) behaviors sometime during PD (odds ratio = 6.08, 95% CI 1.90
      19.49, P = 0.002), and psychosis (odds ratio = 2.45, 95% CI 1.05-5.69, P = 0.04)
      were associated with either ideation. On multivariate logistic regression
      analysis, only increasing severity of depressive symptoms (odds ratio = 2.76, 95%
      CI 1.88-4.07, P < 0.001) predicted suicidal or death ideation. In conclusion,
      active suicidal or death ideation occurs in up to one-third of PD patients.
      Comorbid psychiatric disorders, more than PD-related disease variables, are
      associated with this ideation, highlighting the need for a comprehensive approach
      to the clinical care of PD patients.

PMID- 18618661
TI  - Effectiveness of acupuncture for Parkinson's disease: a systematic review.
AB  - The objective of this review is to assess the clinical evidence for or against
      acupuncture as a treatment for Parkinson's disease (PD). We searched the
      literature using 17 databases from their inception to September 2007 (searched
      again 3rd January 2008), without language restrictions. We included all
      randomized clinical trials (RCTs) regardless of their design. Methodological
      quality was assessed using the Jadad score. Eleven RCTs met all inclusion
      criteria. Three RCTs assessed the effectiveness of acupuncture on Unified
      Parkinson's Disease Rating Scale (UPDRS) compared with placebo acupuncture. A
      meta-analysis of these studies showed no significant effect (n = 96, WMD, 5.7;
      95% CI -2.8 to 14.2, P = 0.19, heterogeneity: tau(2) = 0, chi(2) = 0.97, P =
      0.62, I(2) = 0%). Another six RCTs compared acupuncture plus conventional drugs
      on improvement of symptoms of PD with drugs only. A meta-analysis of two of these
      studies suggested a positive effect of scalp acupuncture (n = 106, RR, 1.46, 95%
      CI = 1.15 to 1.87, P = 0.002; heterogeneity: tau(2) = 0.00, chi(2) = 1.14, P =
      0.29, I(2) = 12%). Two further RCTs tested acupuncture versus no treatment. The
      meta-analysis of these studies also suggested beneficial effects of acupuncture.
      The results of the latter two types of RCTs fail to adequately control for
      nonspecific effects. In conclusion, the evidence for the effectiveness of
      acupuncture for treating PD is not convincing. The number and quality of trials
      as well as their total sample size are too low to draw any firm conclusion.
      Further rigorous trials are warranted.

PMID- 18618662
TI  - Torsional nystagmus induced by subthalamic nucleus stimulation.

PMID- 18618663
TI  - Striatal dopamine transporter imaging correlates with depressive symptoms and
      tower of London task performance in Parkinson's disease.
AB  - We studied whether the (123)I-FP-CIT uptake in the striatum correlates with
      depressive symptoms and cognitive performance in patients with Parkinson's
      disease (PD). Twenty patients with PD without major depression and/or dementia
      (mean age 61.7 +/- 12.7 years) underwent the (123)I-FP-CIT SPECT. Depressive
      symptoms and cognitive performance were assessed in the ON state. The ratios of
      striatal to occipital binding for the entire striatum, putamina, and putamen to
      the caudate (put/caud) index were calculated in the basal ganglia. The
      association between neuropsychiatric measures and dopamine transporter (DAT)
      availability was calculated; multiple regression analysis was used to assess
      association with age and disease duration. We found significant correlations
      between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London
      (TOL) task scores and (123)I-FP-CIT uptake in various striatal ROIs. Multiple
      regression analysis confirmed the significant relationship between TOL
      performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between
      MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003).
      Our pilot study results demonstrate that imaging with (123)I-FP-CIT SPECT appears
      to be sensitive for detecting dopaminergic deficit associated with mild
      depressive symptoms and specific cognitive dysfunction in patients with PD, yet
      without a current depressive episode and/or dementia.

PMID- 18618664
TI  - Emergence of Parkinson's disease in essential tremor: a study of the clinical
      correlates in 53 patients.
AB  - Patients with essential tremor (ET) may develop Parkinson's disease (PD);
      however, few studies have examined the clinical features of this combination
      syndrome. Fifty-three patients with ET-PD were studied and compared to 53 PD and
      150 ET patients. Although the latency from onset of ET to PD was brief (<5 years)
      in 38.5%, in a sizable proportion (30.8%), it was very long (>20 years). The
      gender distribution of ET-PD (67.9% male) was identical to that of PD (67.9%
      male), yet differed from that of ET (50.0% male) (P = 0.02). The initial cardinal
      sign of PD was rest tremor in 100% of patients. In ET-PD, the side of greatest
      initial ET severity usually matched that of greatest PD severity (P < 0.05). In
      ET-PD, male gender predominated and the sidedness of the ET and PD usually
      matched. The co-occurrence of the two diagnoses in the same patient may be
      mechanistically related.

PMID- 18618665
TI  - Benign nocturnal alternating hemiplegia of childhood: The first clinical report
      with paroxysmal events home-video recordings.
AB  - Benign familial nocturnal alternating hemiplegia of childhood (BNAHC) is a rare
      disorder characterized by recurrent attacks of hemiplegia, arising from sleep
      without progression to neurological or intellectual impairment. It is distinct
      from the malignant, relatively more common, alternating hemiplegia of childhood
      (AHC), complicated by developmental deterioration, cognitive impairment, and
      permanent neurological deficits such as choreoathetosis. The authors add a new
      case of BNAHC to the pertinent literature and report, for the first time, a video
      with the typical nocturnal hemiplegic attacks in order to improve knowledge about
      this disorder among child neurologists and pediatricians and increase the
      possibility of clarifying its pathogenesis and molecular basis.

PMID- 18618666
TI  - Uric acid in Parkinson's disease.
AB  - Recent studies have provided evidence that uric acid may play a role in the
      development and progression of Parkinson's disease (PD). Uric acid is a natural
      antioxidant that may reduce oxidative stress, a mechanism thought to play a role
      in the pathogenesis of PD. Higher levels of serum urate (SU) may have a
      neuroprotective effect. High SU levels reduced the risk of developing PD and
      correlated with slower PD progression. Among PD patients SU levels were lower as
      compared with controls. The manipulation of SU levels holds promise in the
      treatment of PD. It is possible that a high purine diet in patients with PD may
      slow progression of the disease. Milk and meat consumption as well as exercise
      modify the risk of developing PD possibly through their influence on SU levels.
      In this article, we review the association between PD and SU levels and its
      implication on the management of PD.

PMID- 18618667
TI  - A new in vitro model of the glial scar inhibits axon growth.
AB  - Astrocytes respond to central nervous system (CNS) injury with reactive
      astrogliosis and participate in the formation of the glial scar, an inhibitory
      barrier for axonal regeneration. Little is known about the injury-induced
      mechanisms underlying astrocyte reactivity and subsequent development of an axon
      inhibitory scar. We combined two key aspects of CNS injury, mechanical trauma and
      co-culture with meningeal cells, to produce an in vitro model of the scar from
      cultures of highly differentiated astrocytes. Our model displayed widespread
      morphological signs of astrocyte reactivity, increases in expression of glial
      fibrillary acidic protein (GFAP), and accumulation of GFAP in astrocytic
      processes. Expression levels of scar-associated markers, phosphacan, neurocan,
      and tenascins, were also increased. Importantly, neurite growth from various CNS
      neuronal populations was significantly reduced when neurons were seeded on the
      scar-like cultures, compared with growth on cultures of mature astrocytes.
      Quantification of neurite growth parameters on the scar model demonstrated
      significant reductions in neuronal adhesion and neurite lengths. Interestingly,
      neurite outgrowth of postnatal neurons was reduced to a greater extent than that
      of embryonic neurons, and outgrowth inhibition varied among neuronal populations.
      Scar-like reactive sites and neurite-inhibitory patches were found throughout
      these cultures, creating a patchwork of growth-inhibitory areas mimicking a CNS
      injury site. Thus, our model showed relevant aspects of scar formation and
      produced widespread inhibition of axonal regeneration; it should be useful both
      for examining mechanisms underlying scar formation and to assess various
      treatments for their potential to improve regeneration after CNS injury. (c) 2008
      Wiley-Liss, Inc.

PMID- 18618668
TI  - Down-regulation of neurocan expression in reactive astrocytes promotes axonal
      regeneration and facilitates the neurorestorative effects of bone marrow stromal
      cells in the ischemic rat brain.
AB  - The glial scar, a primarily astrocytic structure bordering the infarct tissue
      inhibits axonal regeneration after stroke. Neurocan, an axonal extension
      inhibitory molecule, is up-regulated in the scar region after stroke. Bone marrow
      stromal cells (BMSCs) reduce the thickness of glial scar wall and facilitate
      axonal remodeling in the ischemic boundary zone. To further clarify the role of
      BMSCs in axonal regeneration and its underlying mechanism, the current study
      focused on the effect of BMSCs on neurocan expression in the ischemic brain.
      Thirty-one adult male Wistar rats were subjected to 2 h of middle cerebral artery
      occlusion followed by an injection of 3 x 10(6) rat BMSCs (n = 16) or phosphate
      buffered saline (n = 15) into the tail vein 24 h later. Animals were sacrificed
      at 8 days after stroke. Immunostaining analysis showed that reactive astrocytes
      were the primary source of neurocan, and BMSC-treated animals had significantly
      lower neurocan and higher growth associated protein 43 expression in the
      penumbral region compared with control rats, which was confirmed by Western blot
      analysis of the brain tissue. To further investigate the effects of BMSCs on
      astrocyte neurocan expression, single reactive astrocytes were collected from the
      ischemic boundary zone using laser capture microdissection. Neurocan gene
      expression was significantly down-regulated in rats receiving BMSC
      transplantation (n = 4/group). Primary cultured astrocytes showed similar
      alterations; BMSC coculture during reoxygenation abolished the up-regulation of
      neurocan gene in astrocytes undergoing oxygen-glucose deprivation (n = 3/group).
      Our data suggest that BMSCs promote axonal regeneration by reducing neurocan
      expression in peri-infarct astrocytes.

PMID- 18618669
TI  - Activation of adenosine A1 receptor-induced neural stem cell proliferation via
      MEK/ERK and Akt signaling pathways.
AB  - Adenosine, a modulator of neuronal function in the mammalian central nervous
      system, exerts a neuroprotective effect via the adenosine A(1) receptor; however,
      its effect on neural stem cells (NSCs) remains unclear. Because adenosine is
      released in response to pathological conditions and NSCs play a key role in
      neuroregeneration, we tested the hypothesis that adenosine is capable of
      stimulating NSC proliferation. We demonstrated that NSCs dominantly express
      adenosine A(1) and A(2B) receptors. Adenosine and the adenosine A(1) receptor
      agonist cyclopentyladenosine (CPA) increased proliferation of NSCs, and this CPA
      induced cell proliferation was attenuated by the A(1) antagonist 8-cyclopentyl
      1,3-dipropylxanthine (DPCPA). CPA also induced phosphorylation of extracellular
      signal-regulated kinase (ERK), mitogen-activated protein kinase/ERK kinase (MEK),
      and Akt, and their phosphorylation was inhibited by DPCPA. In addition, CPA
      induced cell proliferation was inhibited by MEK and Akt inhibitors. These results
      suggest that activation of adenosine A(1) receptor-stimulated proliferation of
      NSCs occurs via MEK/ERK and Akt signaling pathways.

PMID- 18618670
TI  - Fecal calprotectin levels and serological responses to microbial antigens among
      children and adolescents with inflammatory bowel disease.
AB  - BACKGROUND: Noninvasive, sensitive, and specific tools for early identification
      of chronic inflammatory bowel disease (IBD) are needed for clinical practice. The
      aim was to identify new noninvasive test combinations for characterization of IBD
      in children and adolescents by comparing serological responses to microbial
      antigens and fecal calprotectin, a new promising marker for intestinal
      inflammation. METHODS: Our study included 73 children who underwent endoscopies
      because of suspicion of IBD. Their sera were tested for antibodies to the
      Pseudomonas fluorescens-associated sequence I2, a Bacteroides caccae TonB-linked
      outer membrane protein, OmpW, and anti-Saccharomyces cerevisiae (ASCA).
      Simultaneously, samples for fecal calprotectin measurements were obtained from 55
      subjects. RESULTS: IBD was diagnosed in 60 patients (Crohn's disease [CD] in 18
      patients, ulcerative colitis [UC] in 36, and indeterminate colitis [IC] in 6).
      Thirteen children had a non-IBD disease. Fecal calprotectin levels were elevated
      (>or=100 microg/g) more frequently in IBD patients (89%, 39/44) compared to non
      IBD cases (9%, 1/11, P < 0.001). ASCA antibodies in sera were detected in 67%
      (12/18) of patients with CD, in 14% (5/36) of the children with UC, and in 50%
      (3/6) of patients with IC. Seroreactivity for I2 was observed in 42% of the IBD
      patients, this frequency being higher than in non-IBD cases (7.7% seropositive; P
      = 0.025). Serum anti-I2 IgA levels (median absorbances) were higher in those with
      IBD compared to those without gut inflammation (P = 0.039). The combination of
      the measurements of fecal calprotectin and serological responses to microbial
      antigens (ASCA, I2, and OmpW) identified 100% of CD patients (sensitivity 100%,
      specificity 36%, positive predictive value [PPV] 66%, negative predictive value
      [NPV] 100%) and 89% of UC patients (sensitivity 89%, specificity 36%, PPV 77%,
      NPV 57%). CONCLUSIONS: Increased levels of serological responses to microbial
      antigens (ASCA, I2, and OmpW) and fecal calprotectin are evident in both CD and
      UC patients. The combination of these markers provides valuable, noninvasive
      tools for the diagnosis of IBD.

PMID- 18618671
TI  - Genetic predictors of depressive symptoms in cardiac patients.
AB  - Numerous studies suggest that the prevalence of depression is greater among
      cardiac patients than in the general population. However, little attention has
      been paid to the possibility of genetic contributions to depressive symptoms in
      cardiac patients. We conducted a candidate gene study focusing on genes related
      to inflammation, platelet aggregation, endothelial function and omega-3 fatty
      acid metabolism as predictors of depressive symptoms among 977 participants with
      established cardiovascular disease. Results suggested that genetic variation
      related to endothelial dysfunction is predictive of depressive symptoms and that
      endothelial dysfunction may be a novel mechanism contributing to depressive
      symptoms among cardiac patients.

PMID- 18618673
TI  - Development and psychometric testing of the nurses' attitudes toward obesity and
      obese patients (NATOOPS) scale.
AB  - This study was designed to develop and test an instrument to measure nurses'
      attitudes towards obesity and obese adult patients. Items were based on an
      earlier version of the instrument, obesity discrimination research, and clinical
      experience. After content validation of items, the instrument was sent to 1,400
      randomly selected Registered Nurses. Factor analysis yielded a 5-factor solution,
      with 36 items reaching loadings of .4 or greater. Cronbach's alpha was .81 for
      the reduced scale, with a range of .45 to .79 on the five factors. Construct
      validity was supported by significant differences between contrast groups on
      three factors and consistency with underlying theory. Overall the instrument
      demonstrated acceptable psychometric properties and could be used in future
      research.

PMID- 18618672
TI  - Familial aggregation of quantitative autistic traits in multiplex versus simplex
      autism.
AB  - Recent research has suggested that the mode of inheritance for simplex autism
      (SA, one individual in the family affected) may be distinct from that for
      multiplex autism (MA, two or more individuals affected). Since sub clinical
      autistic traits have been observed in "unaffected" relatives of children with
      autism, we explored whether the distributions of such traits in families
      supported differential modes of genetic transmission for SA and MA autism. We
      measured patterns of familial aggregation of quantitative autistic traits (QAT)
      in children and parents in 80 SA families and 210 MA families, using the Social
      Responsiveness Scale. When considering all SA and MA siblings who scored below a
      uniform quantitative (clinical-level) severity threshold, MA brothers exhibited a
      distinct pathological shift in the distribution, compared to SA brothers (P <
      0.0001). Such aggregation of QAT was also observed in fathers but not among
      females in MA families. Significant spousal correlations for QAT-suggestive of
      assortative mating-were observed in both SA and MA families, but neither group
      was characterized by a greater-than-chance level of concordant elevation among
      spousal pairs in this volunteer sample. Among male first degree relatives, there
      exist distinct patterns of QAT manifestation for simplex versus multiplex autism.
      These findings are consistent with the results of molecular genetic studies that
      have suggested differential modes of intergenerational transmission for SA and
      MA. Characterization of QAT and other endophenotypes among close relatives may be
      useful for reducing sample heterogeneity in future genetic and neurobiologic
      studies of autism.

PMID- 18618675
TI  - 17beta-estradiol attenuates hyperoxia-induced apoptosis in mouse C8-D1A cell
      line.
AB  - In premature infants, oxygen free radicals generated following neonatal
      resuscitation are associated with subsequent diseases such as retinopathy of
      prematurity and bronchopulmonary dysplasia. Recent studies in brain tissue
      samples have shown that nonphysiologic oxygen levels play a key role in induction
      of apoptosis in the developing brain. Estrogen is a well-established agent in
      neuroprotection and, therefore, is thought to be neuroprotective even in the
      premature brain. Astrocytes appear to have a critical role in protection and
      survival of neurons in the brain. As one of the glial cell types, they have a
      great potential for possible involvement in the mediation of estrogen
      neuroprotective effects. The aim of our study was to analyze whether astrocytes
      in cell cultures are damaged by hyperoxia and whether 17beta-estradiol (E2) can
      protect them against apoptosis. Additionally, we investigated the mechanism of
      the protection by E2, hypothesizing that it is mediated through extracellular
      signal-regulated kinase (ERK1/2). Cells underwent eightfold more apoptosis when
      cultivated in hyperoxia compared with normoxia. Addition of E2 reduced apoptosis
      in hyperoxia by more than 50%. Levels of ERK1/2 and phosphorylated ERK1/2 were
      increased after hyperoxia compared with normoxia. Preincubation with E2 prior to
      exposure to hyperoxia resulted in decreased levels of ERK1/2 and pERK1/2.
      Hyperoxia induces apoptosis in C8-D1A cells, and E2 seems to be a protecting
      factor for astrocytes in hyperoxia. This effect is not mediated through up
      regulation of pERK1/2.

PMID- 18618676
TI  - Oral budesonide for the therapy of post-liver transplant de novo inflammatory
      bowel disease: a case series and systematic review of the literature.
AB  - BACKGROUND: The therapy for posttransplant IBD is clinically challenging.
      Patients receiving liver transplants are immunosuppressed to prevent rejection,
      but via an unknown mechanism develop de novo IBD in spite of receiving some of
      the same medications used for therapy in traditional IBD. In the published
      literature most of the patients who developed de novo IBD were treated with
      traditional corticosteroids. Exposure to systemic corticosteroids increases risks
      of infection, diabetes mellitus, and osteoporosis among other complications.
      Budesonide, a luminally active steroid with low systemic absorption, is an
      established therapeutic agent for IBD that should receive special considerations
      as first-line therapy in this patient population. METHODS: We describe 3 cases of
      de novo IBD after liver transplantation. None of these patients had a history of
      IBD prior to their transplant. All 3 were treated with oral budesonide in lieu of
      systemic corticosteroids. Additionally, a Medline MeSH search was performed using
      the terms "inflammatory bowel disease" and "liver transplant" as part of a
      systematic review of the literature. RESULTS: All 3 cases of de novo post
      transplant IBD went into clinical remission with oral budesonide. The Medline
      search ultimately revealed 19 case reports, case series or retrospective reviews
      on de novo post liver transplant IBD. Most reports focused on the diagnosis and
      risk factors and did not have an emphasis on therapy. CONCLUSIONS: Given the
      track record for budesonide in traditional IBD, and its documented efficacy and
      systemic steroid-sparing benefit, in our opinion this drug should be considered
      first-line therapy for de novo posttransplant IBD.

PMID- 18618674
TI  - Behavior of hippocampal stem/progenitor cells following grafting into the injured
      aged hippocampus.
AB  - Multipotent neural stem/progenitor cells (NSCs) from the embryonic hippocampus
      are potentially useful as donor cells to repopulate the degenerated regions of
      the aged hippocampus after stroke, epilepsy, or Alzheimer's disease. However, the
      efficacy of the NSC grafting strategy for repairing the injured aged hippocampus
      is unknown. To address this issue, we expanded FGF-2-responsive NSCs from the
      hippocampus of embryonic day 14 green fluorescent protein-expressing transgenic
      mice as neurospheres in vitro and grafted them into the hippocampus of 24-month
      old F344 rats 4 days after CA3 region injury. Engraftment, migration, and
      neuronal/glial differentiation of cells derived from NSCs were analyzed 1 month
      after grafting. Differentiation of neurospheres in culture dishes or after
      placement on organotypic hippocampal slice cultures demonstrated that these cells
      had the ability to generate considerable numbers of neurons, astrocytes, and
      oligodendrocytes. Following grafting into the injured aged hippocampus, cells
      derived from neurospheres survived and dispersed, but exhibited no directed
      migration into degenerated or intact hippocampal cell layers. Phenotypic analyses
      of graft-derived cells revealed neuronal differentiation in 3%-5% of cells,
      astrocytic differentiation in 28% of cells, and oligodendrocytic differentiation
      in 6%-10% cells. The results demonstrate for the first time that NSCs derived
      from the fetal hippocampus survive and give rise to all three CNS phenotypes
      following transplantation into the injured aged hippocampus. However, grafted
      NSCs do not exhibit directed migration into lesioned areas or widespread neuronal
      differentiation, suggesting that direct grafting of primitive NSCs is not
      adequate for repair of the injured aged brain without priming the
      microenvironment.

PMID- 18618677
TI  - Spirometry in an unselected group of 6-year-old children: the DARC birth cohort
      study.
AB  - This study presents reference equations for spirometric parameters in 6-year-old
      children and evaluates the ability of spirometry to discriminate healthy children
      from children with asthma. Baseline spirometry and respiratory symptoms were
      assessed in 404 children participating in a longitudinal birth cohort study.
      Children with known asthma, possible asthma and a control group also performed
      bronchodilator measurements. At least two acceptable flow-volume curves at
      baseline were obtained by 368/404 children (91%). The two best values for FEV1
      and FVC were within 5% of each other in 88% and 83% of children, respectively.
      Linear regression analyses for 242 children included in the reference population
      demonstrated height to be the main predictor of all spirometric indices except
      FEV1/FVC. FEV1, FEV75, and FVC correlated reasonably to anthropometric data in
      contrast to flow parameters. Gender differences were found for FEV1, FVC, and
      FEV75, but not for flow parameters. Asthma was diagnosed in 25/404 children.
      Baseline lung function in healthy children and children with asthma overlapped,
      although asthmatic children could be discriminated to some extent. Bronchodilator
      tests showed a difference in Delta FEV1(mean) between healthy children and
      children with asthma (3.1% vs. 6.1%, P < 0.05). At a cut-off point of Delta FEV1
      = 7.8%, bronchodilator tests had a sensitivity of 46% and a specificity of 92%
      for current asthma. Spirometry including bronchodilator measurements was
      demonstrated to be feasible in 6-year-old children and reference values were
      determined. Spirometry aids the diagnosis of asthma in young children, but
      knowledge on sensitivity and specificity of these measurements is a prerequisite.

PMID- 18618679
TI  - Genetically engineered charge modifications to enhance protein separation in
      aqueous two-phase systems: Electrochemical partitioning.
AB  - We have examined the effect of genetically engineered charge modifications on the
      partitioning behavior of proteins in dextran/polyethylene glycol two-phase
      systems containing potassium phosphate. By genetically altering a protein's
      charge, the role of charge on partitioning can be assessed directly without the
      need to modify the phase system. The charge modifications used are of two types:
      Charged tails of polyaspartic acid fused to beta-galactosidase and charge-change
      point mutations of T4 lysozyme which replace positive lysine residues with
      negative glutamic acids. The partition coefficient K(p) for these proteins was
      related to measured interfacial potential differences Deltaphi using the simple
      thermodynamic model, In K(p) = In K(o) + (F/RT)Z(p) deltaphi. The protein net
      charge Z(p) was determined using the Henderson-Hasselbalch relationship with
      modifications based on experimentally determined titration and isoelectric point
      data. It was found that when the electropartitioning term Z(p) deltaphi was
      varied by changing the pH, the partitioning of T4 lysozyme was quantitatively
      described by the thermodynamic model. The beta-galactosidase fusions displayed
      qualitative agreement, and although less than predicted, the partitioning
      increased more than two orders of magnitude for the pH range examined. Changes in
      the partitioning of lysozyme due to the various mutations agreed qualitatively
      with the thermodynamic model, but with a smaller than expected dependence on the
      estimated charge differences. The beta-galactosidase fusions, on the other hand,
      did not display a consistent charge based trend, which is likely due either to
      the enzyme's large size and complexity or to nonelectrostatic contributions from
      the tails. The lack of quantitative fit with the model described above suggests
      that the assumptions made in developing this model are oversimplified. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18618680
TI  - Unified kinetic treatment for growth on dual nutrients.
AB  - This paper presents a new formulation for the analysis of growth kinetics on
      multiple nutrients. The baseline for the theory is the concept that a
      noninteractive growth process occurs among perfectly substitutable nutrients if
      the locus of points of the substrate concentrations producing equal growth rate
      is linear. A deviation function is then defined with respect to this base case,
      and several models for this function are suggested. The underlying theory is
      taken by analogy with mixture thermodynamics. The proposed formulation is tested
      against data in the literature on growth under substitutable and complementary
      substrate mixtures. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618681
TI  - Degradation of pencillin-V in fermentation media.
AB  - In Industrial production of penicillin there is a noticeable loss of the product
      through degradation reactions. It is shown that the degradation of penicillin-V,
      both in a complex and in a chemically defined medium, can be separated into a
      phosphate-catalyzed conversion of penicillin-V to penicilloic-V acid, overlaid by
      at least one other reaction in which penicillin V is degraded to as yet unknown
      products. Parameter values for the phosphatecatalyzed degradation are found to be
      independent of the type of fermentation medium. The rate of formation of other
      degradation products of penicillin-V is found to be significantly higher in a
      complex fermentation medium with corn-steep liquor in a chemically defined
      medium. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618682
TI  - On-line characterization of a hybridoma cell culture process.
AB  - The on-line determination of the physiological state of a cell culture process
      requires reliable on-line measurements of various parameters and calculations of
      specific rates from these measurements. The cell concentration of a hybridoma
      culture was estimated on-line by measuring optical density (OD) with a laser
      turbidity probe. The oxygen uptake rate (OUR) was determined by monitoring
      dynamically dissolved oxygen concentration profiles and closing oxygen balances
      in the culture. The base addition for neutralizing lactate produced by cells was
      also monitored on-line via a balance. Using OD and OUR measurements, the specific
      growth and specific oxygen consumption rates were determined on-line. By
      combining predetermined stoichiometric relationships among oxygen and glucose
      consumption and lactate production, the specific glucose consumption and lactate
      production rates were also calculated on-line. Using these on-line measurements
      and calculations, the hybridoma culture process was characterized on-line by
      identifying the physiological states. They will also facilitate the
      implementation of nutrient feeding strategies for fed-batch and perfusion
      cultures. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618683
TI  - A fast bioassay for phytotoxicity measurements using immobilized photosynthetic
      membranes.
AB  - The potential of thylakoid membranes immobilized in an albumin-glutaraldehyde
      crosslinked matrix in a fast bioassay for phytotoxicity measurements in aqueous
      samples is studied. Free and immobilized preparations are compared for their
      electron transport activity measured as the initial rate of oxygen evolution with
      2,5-cichlorobenzoquinone as the artificial electron acceptor. Immobilized
      thylakoids were much stable under storage conditions; in the dark, at 4 degrees
      C, they were fully stable in terms of photosynthetic activity for a period of 200
      h. The immobilized membranes were as sensitive as the free thylakoids for the
      detection of most of the compounds tested (metal cations, sulfite, nitrite, and
      herbicides), all known as inhibitors of photosynthetic electron transport. In
      some instances, the immobilized preparations were even more sensitive than the
      free counterparts. The sensitivity could be further increased by lowering
      chlorophyll concentration in the assay. The short incubation period required (
      approximately 10 to 15 min) and the small volume of the assay (3 mL) suggest that
      this type of material should be useful in the detection of locations or effluents
      with phytotoxic character. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618684
TI  - Biochemistry of growth inhibition by ammonium ions in mammalian cells.
AB  - The intracellular pool of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine
      has been shown to act as a central target during the inhibitory action of
      ammonium ions in vitro cultivated mammalian cell cultures. This pool has been
      demonstrated to be elevated at the end of a batch cultivation and very quickly as
      a response to exogenously applied ammonium chloride by using four different cell
      lines (hybridoma, BHK, CHO, and Ltk(-)929). The amount of enlarged UDP
      aminohexoses is correlated to the inhibitor concentration and additionally
      dependent on the cell line. The formation of the UDP sugars is associated with a
      transient reduction of the UTP pool. Moreover, the quick formation of UDP-GNAc is
      strictly dependent on the presence of glucose and ammonium. Both metabolites act
      as biochemical precursors. Additionally, the formation of UDP-GNAc after ammonium
      application has been shown to increase with an elevated cultivation pH and to be
      independent of the inhibition of transcription and translation processes. The
      intracellular amount of UDP-GNAc correlates with the level of growth inhibition
      in mammalian cell lines. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618685
TI  - Heterogeneity of biofilms in rotating annular reactors: Occurrence, structure,
      and consequences.
AB  - A rotating annular reactor (Roto Torque) was used for qualitative and
      quantitative studied on biofilm heterogeneity. In contrast to the classic image
      of biofilms as smooth, homogeneous layers of biomass on a substratum, studies
      using various pure and mixed cultures consistently revealed more-dimensional
      structures that resembled dunes and ridges, among others. These heterogeneities
      were categorized and their underlying causes analyzed. Contrary to expectations,
      motility of the microorganisms not a decisive factor in determining biofilm
      homogeneity. Small Variations in substratum geometry homogeneity. Small
      variations in substratum geometry and flow patterns were clearly reflected in the
      biofilm pattern. Nonhomogeneous flow and shear patterns in the reactor, together
      with inadequate mixing resulted in significant, position-dependent differences in
      surface growth. It was therefore not possible to take representative samples of
      the attached biomass. Like many other types of reactors, the Roto Torque reactor
      is valuable for qualitative and morphological biofilm experiments but less
      suitable for quantitative physiological and kinetics studies using attached
      microorganisms. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618686
TI  - Kinetics of taxol production, growth, and nutrient uptake in cell suspensions of
      Taxus cuspidata.
AB  - Cell culture of Taxus cuspidata may represent an alternative to extraction of
      bark as a source of taxol and related taxanes. Cell suspensions of a cell line of
      T. cuspidata were grown for 44 days in shake flasks containing B5C2 medium.
      Throughout the growth cycle, fresh and dry weight accumulation, taxol yield on a
      dry weight basis, taxol accumulation in the medium, pH and pigmentation variation
      in the medium, as well as the uptake of sucrose, glucose, fructose, nitrate, and
      inorganic phosphate from the culture medium were examined. The results showed
      that the growth was relatively slow (doubling times of 17 and 20 days for fresh
      and dry weight, respectively), and taxol accumulation in the cells was non-growth
      related (higher in the stationary phase) and at relatively low levels (up to 4
      mug/g of the extracted dry weight). Taxol concentration in the medium had two
      peaks: one during the early (0.4mug/mL) and another during the late (0.1-mug/mL)
      parts of the growth cycle. On a volumetric basis, the average total amount of
      taxol produced during the stationary phase (day 38) was 0.15 mug/mL, of which
      approximately 66% was in the medium and 34% was in the cells. Total carbohydrate
      uptake was closely associated with the increase in dry biomass. Sucrose was
      apparently extracellularly hydrolyzed after the first 6 days of culture; glucose
      was used before fructose. Nitrate was assimilated throughout the growth cycle,
      but phosphate was absorbed within the first week of culture. The pH variation
      showed an initial drop followed by a trend toward alkalinization for most of the
      growth period. Dark pigmentation in the medium increased progressively,
      particularly during the stationary phase. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618687
TI  - Biological destruction of CCI(4): II. Kinetic modeling.
AB  - A denitrifying consortium capable of transforming carbon tetrachloride (CCI(4))
      was cultured from an aquifer soil sample from the U.S. Department of Energy's
      Hanford Site in southeastern Washington State. A mathematical description of the
      kinetics of CCI(4) destruction by this microbial consortium is presented, and its
      prediction are compared to experimental data. The model successfully predicted
      the concentrations of acetate, nitrate, nitrite, biomass, and CCI(4) for all 12
      experiments (a total of 60 concentration-vs.-time data sets). In addition, no
      statistically significant interactions exist between parameter values and
      individual test conditions. The ability of the model to predict the results of a
      treatability test for CCI(4) degradation in Hanford groundwater, without
      adjusting any model parameters, is discussed. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618688
TI  - Interactions of microbial biofilms with toxic trace metals: 1. Observation and
      modeling of cell growth, attachment, and production of extracellular polymer.
AB  - Adsorbent surfaces in natural and engineered systems are frequently modifies by
      bacterial attachment, growth of a biofilm, and bacterial production of
      extracellular polymer. Attached cells or sorbed polymers may alter the metal
      binding characteristics of the supporting substratum and influence metal
      partitioning. The interdependent behavior of toxic trace metal partitioning and
      biofilm development requires description of the interaction between cell growth
      with its accompanying polymer production and metal speciation. In this article,
      the first of a two part series, a mechanistic model is developed to describe the
      growth of a film-forming bacterium which adheres to a substratum through the
      production of extracellular biopolymers. Each bacterial cell was modeled as a two
      component structure consisting of active cell mass and biopolymer. The biopolymer
      component was further divided into cell-associated and dissolved categories to
      distinguish which remained naturally bound to cell surfaces from that which did
      not. Use of this structured model permitted independent description of the
      dynamics of cell growth, and polymer production, both of which may influence
      trace metal behavior. Employing parameters obtained from independent experiments
      as well as published values, the model satisfactorily predicts experimental
      observations of bacterial growth, attachment and detachment, biopolymer
      production, and adsorption of polymer onto solid (glass) surfaces. The model
      stimulated transient and steady-state biofilm systems equally well. In the second
      article in this series, we describe how this model may be extended and utilized
      to make predictions of the behavior of transient and steady-state biofilm systems
      in the presence of a toxic transition metal(Pb). (c) 1994 John Wiley & Sons, Inc.

PMID- 18618689
TI  - Interactions of microbial biofilms with toxic trace metals: 2. Prediction and
      verification of an integrated computer model of lead (II) distribution in the
      presence of microbial activity.
AB  - The interfacial interactions of a toxic trace metal, Pb, with a surface modified
      by a marine film-forming bacterium, Psedomonas atlantica, were predicted by a
      structured biofilm model used in conjunction with a chemical speciation model.
      The validity of the integrated model was tested for batch and continuous
      operations. Dynamic responses of the biophase due to transient lead concentration
      increases were also stimulated. The reasonable pre dictions achieved by the model
      demonstrate its utility in describing trace metal distributions in complex
      systems where the adsorption properties of inorganic surfaces are modified by
      adherent bacteria production of extracellular polymers. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18618690
TI  - Saccharification and fermentation of Sugar Cane bagasse by Klebsiella oxytoca P2
      containing chromosomally integrated genes encoding the Zymomonas mobilis ethanol
      pathway.
AB  - Pretreatment of sugar cane bagasse is essential for a simultaneous
      saccharification and fermentation (SSF) process which uses recombinant Klebsiella
      oxytoca strain P2 and Genencor Spezyme CE. Strain P2 has been genetically
      engineered to express Zymomonas mobilis genes encoding the ethanol pathway and
      retains the native ability to transport and metabolize cellobiose (minimizing the
      need for extracellular cellobiase). In SSF studies with this organism, both the
      rate of ethanol production and ethanol yield were limited by saccharification at
      10 and 20 filter papaer units (FPU) g(-1) acid-treated bagasse. Dilute slurries
      of biomass were converted to ethanol more efficiently (over 72% of theoretical
      yield) in simple batch fermentations than slurries containing high solids albeit
      with the production of lower levels of ethanol. With high solids (i.e., 160 g
      acid-treated bagasse L(-1)), a combination of 20 FPU cellulase g(-1) bagasse,
      preincubation under saccharification conditions, and additional grinding (to
      reduce particle size) were required to produce ca. 40 g ethanol L(-1).
      Alternatively, almost 40 g ethanol L(-1) was produced with 10 FPU cellulase g(-1)
      bagasse by incorporating a second saccharification step (no further enzyme
      addition) followed by a second inoculation and short fermentation. In this way, a
      theoretical ethanol yield of over 70% was achieved with the production of 20 g
      ethanol 800 FPU(-1) of commercial cellulase. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618691
TI  - Biodegradation process development using a bacterial cytochrome in vivo.
AB  - Pseudomonas putida PpG786 that contains the inducible enzyme system cytochrome P
      450(cam) is considered for use as specialized biomass fore detoxification of
      hazardous hydrocarbons. The test substrate 1,2-dibromochloropropane (DBCP) is
      used to assess the organohalide degradation activity of P. Putida PpG786.
      Activity was found to be a strong function of intracellular heme content,
      variables which affect the culturing and processing of the cells, and oxygen
      tension in the degradation incubation medium. The lifetime for maintaing active
      biomass in chemostat washout operation, after including substrate was removed and
      then restarted, was also studied. These results indicate that initial activity of
      the P. Putida biomass is high enough, and decays slowly enough, so that
      industrial wastewater treatment at the operating conditions of a sequencing batch
      reactor (SBR) could remove hazardous compounds. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618692
TI  - Optimization of microbial poly(3-hydroxybutyrate) recover using dispersions of
      sodium hypochlorite solution and chloroform.
AB  - Optimization was carried out for the recovery of microbiol poly(3
      hydroxybutyrate) (PHB) from Alcaligenes eutrophus. This process involved the use
      of a dispersion made of sodium hypochlorite solution and chloroform. The
      dispersion enabled us to take advantage of both differential digestion by
      hypochlorite and solvent extraction by chloroform. The PHB recovery (%) from cell
      powder was maximized using a 30% hypochlorite concentration, a 90-min treatment
      time, and a 1:1 (v/v) chloroform-to-aqueous-phase ratio. Under these optimal
      conditions, the recovery was about 91% and the purity of recovered PHB was higher
      than 97%. The number average molecular weight, M(n) of recovered PHB was about
      300,000 and the weight average molecular weight M(w) was about 1,020,000,
      compared to the original M(n) of 530,000 and M(w) of 1,272,000. The moderate
      decrease in both M(n) and M(w) might be ascribed to the shielding effect of
      chloroform. In addition, the relatively small decrease in M(w) probably resulted
      from the loss of short PHB chains which might be water soluble. The crystallinity
      of recovered PHB was in the range of 60 to 65%although a slightly higher
      crystallinity was observed when the dispersion was used. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18618693
TI  - The ratio of matrix metalloproteinase to E-cadherin expression: a pilot study to
      assess mRNA and protein expression among African American prostate cancer
      patients.
AB  - BACKGROUND: We assessed the expression of Matrix Metalloproteinase (MMP) to E
      cadherin (M/E ratio) to determine the correlation of gene expression with
      pathologic variables and outcome in a cohort of African American (AA) prostate
      cancer patients. METHODS: Tumors from formalin-fixed, paraffin embedded RP
      specimens were examined. Gleason scores were 6, 7, and >or=8 in 7, 16, 13 tumors,
      respectively. Pathologic stage was organ confined (pT2) in 18 and advanced (>pT2)
      in 18 tumors. A colorimetric mRNA in situ hybridization (ISH) assay was performed
      using biotinylated anti-sense oligonucleotide probes for MMP 2 and 9, as well as
      for E-cadherin gene transcripts. Immunohistochemistry (IHC) was performed
      utilizing specific monoclonal antibodies to detect the above genes. Image
      analysis was performed to determine the intensity of both mRNA and protein
      expression. Two reviewers analyzed ISH gene expression independently. RESULTS:
      The M/E expression ratio was significantly increased at the invasive edge (but
      not the center) of tumors of higher Gleason score (P = 0.02 and 0.0008) and
      pathologic stage (P = 0.0001 and <0.0001) when examined by both ISH and IHC.
      Significant variability in ISH staining interpretation was noted within and among
      the two study reviewers. An M/E ratio >2.5 was associated with biochemical
      recurrence after radical prostatectomy in addition to tumor pathologic stage
      subsequent to univariate statistical analysis. CONCLUSIONS: The M/E ratio
      characterizes an important aspect of the molecular phenotype associated with the
      histologic progression of prostate cancer among African American prostate cancer
      patients. A larger comparative study is required to determine potential racial
      variation and prognostic significance of gene expression.

PMID- 18618694
TI  - The first high pH structure of Escherichia coli aspartate transcarbamoylase.
AB  - The activity and cooperativity of Escherichia coli aspartate transcarbamoylase
      (ATCase) vary as a function of pH, with a maximum of both parameters at
      approximately pH 8.3. Here we report the first X-ray structure of unliganded
      ATCase at pH 8.5, to establish a structural basis for the observed Bohr effect.
      The overall conformation of the active site at pH 8.5 more closely resembles the
      active site of the enzyme in the R-state structure than other T-state structures.
      In the structure of the enzyme at pH 8.5 the 80's loop is closer to its position
      in R-state structures. A unique electropositive channel, comprised of residues
      from the 50's region, is observed in this structure, with Arg54 positioned in the
      center of the channel. The planar angle between the carbamoyl phosphate and
      aspartate domains of the catalytic chain is more open at pH 8.5 than in ATCase
      structures determined at lower pH values. The structure of the enzyme at pH 8.5
      also exhibits lengthening of a number of interactions in the interface between
      the catalytic and regulatory chains, whereas a number of interactions between the
      two catalytic trimers are shortened. These alterations in the interface between
      the upper and lower trimers may directly shift the allosteric equilibrium and
      thus the cooperativity of the enzyme. Alterations in the electropositive
      environment of the active site and alterations in the position of the catalytic
      chain domains may be responsible for the enhanced activity of the enzyme at pH
      8.5.

PMID- 18618696
TI  - An engineered folded PLP-bound monomer of Treponema denticola cystalysin reveals
      the effect of the dimeric structure on the catalytic properties of the enzyme.
AB  - Cystalysin, a dimeric pyridoxal 5'-phosphate (PLP)-dependent lyase, is a
      virulence factor of the human oral pathogen Treponema denticola. Guided by
      bioinformatic analysis, two interfacial residues (Leu57 and Leu62) and an active
      site residue (Tyr64*), hydrogen-bonded with the PLP phosphate group of the
      neighboring subunit, have been mutated. The wild-type and the L57A, L62A, Y64*A,
      L57A/L62A, L57A/Y64*A, L57A/L62A/Y64*A mutants, all having a C-terminal histidine
      tag, have been constructed, expressed, and purified. The impact of these
      mutations on the dimeric state of cystalysin in the apo- and holo-form has been
      analyzed by size-exclusion chromatography. The results demonstrate that (i) Leu57
      is more critical than Leu62 for apodimer formation, (ii) Tyr64*, more than Leu62,
      interferes with dimerization of holocystalysin without affecting that of
      apoenzyme, (iii) while each single mutation is inadequate in significantly
      altering the extent of monomerization of both apo- and holo-cystalysin, their
      combination leads to species which remain in a folded monomeric state at a
      reasonably high concentration in both the apo- and holo-forms. Although L57A/L62A
      or L57A/Y64*A, even to a different extent, are stimulated to dimer formation in
      the presence of either unproductive or productive ligands, L57A/L62A/Y64*A
      remains prevalently monomer at a concentration up to 50 microM. Kinetic analyses
      show that in this monomeric species the alpha,beta-eliminase, alanine racemase,
      and D-alanine half-transaminase activities are almost abolished, while the L
      alanine half-transaminase activity is slightly enhanced when compared with that
      of wild-type. The structural basis of the stereospecific transaminase activity
      displayed by the engineered folded PLP-bound monomer has been analyzed and
      discussed.

PMID- 18618695
TI  - Rapid comparison of properties on protein surface.
AB  - The mapping of physicochemical characteristics onto the surface of a protein
      provides crucial insights into its function and evolution. This information can
      be further used in the characterization and identification of similarities within
      protein surface regions. We propose a novel method which quantitatively compares
      global and local properties on the protein surface. We have tested the method on
      comparison of electrostatic potentials and hydrophobicity. The method is based on
      3D Zernike descriptors, which provides a compact representation of a given
      property defined on a protein surface. Compactness and rotational invariance of
      this descriptor enable fast comparison suitable for database searches. The
      usefulness of this method is exemplified by studying several protein families
      including globins, thermophilic and mesophilic proteins, and active sites of TIM
      beta/alpha barrel proteins. In all the cases studied, the descriptor is able to
      cluster proteins into functionally relevant groups. The proposed approach can
      also be easily extended to other surface properties. This protein surface-based
      approach will add a new way of viewing and comparing proteins to conventional
      methods, which compare proteins in terms of their primary sequence or tertiary
      structure.

PMID- 18618697
TI  - NMR structural studies of the Ste11 SAM domain in the dodecyl phosphocholine
      micelle.
AB  - The sterile alpha-motif (SAM), a relatively small ( approximately 70 amino acids)
      interaction domain, is found in a variety of proteins involved in cell signaling,
      transcription regulation, and scaffolding. The Ste11 protein kinase from the
      mitogen activated protein kinase (MAPK) signaling cascades of the budding yeast
      is regulated by a SAM domain located at the N-terminus of full-length protein. In
      solution, the Ste11 SAM domain exists as a well-folded dimeric structure that is
      involved in interaction with the cognate SAM domain from an adaptor protein
      Ste50. In this work, we show that the Ste11 SAM domain has an intrinsic affinity
      towards the lipid membranes. The solution conformation of the Ste11 SAM
      determined in perdeuterated DPC micelle, using NMR spectroscopy, is defined by
      five helices of different lengths connected by a number of loops. In the micelle
      bound state, the non-polar and aromatic residues of the Ste11 SAM lack a native
      like packing and are presumably engaged in interactions with the micelle. Using
      two different paramagnetic doxyl-lipids; we have mapped out localization of Ste11
      SAM residues at the micelle surface. Most of the residues appear to localize at
      the interfacial region of the micelle. However, a number of non-polar residues
      from the central region of the domain are found to be located inside the core of
      the micelle including residues from the helix 4 and a loop between helix 2 and
      helix 3. Isothermal titration calorimetry studies demonstrate that a facile
      insertion of the Ste11 SAM into the DPC micelle is primarily driven by a large
      change in enthalpy, -50 kcal/mol with an apparent equilibrium association
      constant (Ka) of 7.86 x 10(6) M(-1). Interestingly, an interfacial mutant L60R of
      the Ste11 SAM lacking the dimeric structure does not show detectable interactions
      with the lipid micelle. The micelle-bound structure of the Ste11 SAM domain
      described in this work may have potential implications in the regulation of MAPK
      signaling whereby positioning of the Ste11 protein in close proximity to the
      membrane may facilitate efficient phosphorylation of the Ste11 kinase by the
      membrane attached upstream Ste20/pak kinase.

PMID- 18618698
TI  - Signaling pathways of PDZ2 domain: a molecular dynamics interaction correlation
      analysis.
AB  - PDZ domains are found in many signaling proteins. One of their functions is to
      provide scaffolds for forming membrane-associated protein complexes by binding to
      the carboxyl termini of their partners. PDZ domains are thought also to play a
      signal transduction role by propagating the information that binding has occurred
      to remote sites. In this study, a molecular dynamics (MD) simulation-based
      approach, referred to as an interaction correlation analysis, is applied to the
      PDZ2 domain to identify the possible signal transduction pathways. A residue
      correlation matrix is constructed from the interaction energy correlations
      between all residue pairs obtained from the MD simulations. Two continuous
      interaction pathways, starting at the ligand binding pocket, are identified by a
      hierarchical clustering analysis of the residue correlation matrix. One pathway
      is mainly localized at the N-terminal side of helix alpha1 and the adjacent C
      terminus of loop beta1-beta2. The other pathway is perpendicular to the central
      beta-sheet and extends toward the side of PDZ2 domain opposite to the ligand
      binding pocket. The results complement previous studies based on multiple
      sequence analysis, NMR, and MD simulations. Importantly, they reveal the
      energetic origin of the long-range coupling. The PDZ2 results, as well as the
      earlier rhodopsin analysis, show that the interaction correlation analysis is a
      robust approach for determining pathways of intramolecular signal transduction.

PMID- 18618699
TI  - Molecular dynamics simulation of the acidic compact state of apomyoglobin from
      yellowfin tuna.
AB  - A molecular model of the acidic compact state of apomyoglobin (A-state) from
      yellowfin tuna was obtained using molecular dynamics simulations (MD) by
      calculating multiple trajectories. To cause partial unfolding within a reasonable
      amount of CPU time, both an acidic environment (pH 3 and 0.15M NaCl) and a
      temperature jump to 500 K were needed. Twenty-five acidic structures of
      apomyoglobin were generated by MD, 10 of them can be clustered by RMSD in an
      average structure having a common hydrophobic core as was reported for acidic
      sperm whale apomyoglobin, with shortened helices A,G,E, and H (the helix A
      appears to be translated along the sequence). Prolonging the MD runs at 500 K did
      not cause further substantial unfolding, suggesting that the ensemble of
      generated structures is indicative of a region of the conformational space
      accessible to the apoprotein at acidic pH corresponding to a local energy
      minimum. The comparison of experimentally determined values of specific
      spectroscopic properties of the apomyoglobin in acidic salt conditions with the
      expected ones on the basis of the MD generated structures shows a reasonable
      agreement considering the characteristic uncertainties of both experimental and
      simulation techniques. We used frequency domain fluorometry, acrylamide
      fluorescence quenching, and fluorescence correlation spectroscopy together with
      far UV circular dichroism to estimate the helical content, the Stern-Volmer
      quenching constant and the radius of gyration of the protein. Tuna apomyoglobin
      is a single tryptophan protein and thus, interpretation of its intrinsic
      fluorescence is simpler than for other proteins. The high sensitivity of the
      applied fluorescence techniques enabled experiments to be performed under very
      dilute conditions, that is, at concentrations of subnanomolar for the FCS
      measurements and 6 muM for the other fluorescence measurements. As high
      concentrations of proteins can strongly affect the association equilibrium among
      partially unfolded states, fluorescence techniques can provide complementary
      information with respect to other techniques requiring higher sample
      concentrations, such as NMR. The analysis of exposed hydrophobic regions in each
      of the MD-generated acidic structures reveals potential candidates involved in
      the aggregation processes of apomyoglobin in the acidic compact state. Our
      investigation represents an effective model system for studying amyloid fibril
      formation found in important diseases that are believed to proceed via
      aggregation of protein in the molten globule state.

PMID- 18618700
TI  - Thermodynamics of calmodulin binding to cardiac and skeletal muscle ryanodine
      receptor ion channels.
AB  - The skeletal muscle (RyR1) and cardiac muscle (RyR2) ryanodine receptor calcium
      release channels contain a single, conserved calmodulin (CaM) binding domain, yet
      are differentially regulated by CaM. Here, we report that high-affinity
      [(35)S]CaM binding to RyR1 is driven by favorable enthalpic and entropic
      contributions at Ca(2+) concentrations from <0.01 to 100 microM. At 0.15 microM
      Ca(2+), [(35)S]CaM bound to RyR2 with decreased affinity and binding enthalpy
      compared with RyR1. The rates of [(35)S]CaM dissociation from RyR1 increased as
      the temperature was raised, whereas at 0.15 microM Ca(2+) the rate from RyR2 was
      little affected. The results suggest major differences in the energetics of CaM
      binding to and dissociation from RyR1 and RyR2.

PMID- 18618701
TI  - Electrostatics-defying interaction between arginine termini as a thermodynamic
      driving force in protein-protein interaction.
AB  - Apparent electrostatics-defying clustering of arginines attributed as screening
      effect of solvent is in this study examined as a possible thermodynamic driving
      force in protein-protein interaction. A dataset of 266 protein dimers is found to
      have approximately 22% arginines mutually paired and approximately 17% pairs in
      interaction across interfaces and thus putative "hotspots" of protein-protein
      interaction. The pairing, uncorrelated with inter or intramolecular context,
      could be contributing in protein folding as well, and, uncorrelated with solvent
      access, could be driven by effects that are generic to solvent and protein
      structures. Mutually stacked at shorter distances but in diverse geometrical
      modes otherwise, the cations tend to be in gross deficit of hydrogen-bond
      partners, and contributing electrostatics across protein-protein interface that,
      on average, is repulsive for protein-protein interaction. Embedded in local
      environment enriched in polarizable residues, aromatic, aliphatic, and anionic,
      the arginines may contribute to protein-protein interaction via environmental
      polarization response to electrostatics of cation clustering, a possible new
      principle in molecular recognition.

PMID- 18618702
TI  - Prediction of turn types in protein structure by machine-learning classifiers.
AB  - We present machine learning approaches for turn prediction from the amino acid
      sequence. Different turn classes and types were considered based on a novel turn
      classification scheme. We trained an unsupervised (self-organizing map) and two
      kernel-based classifiers, namely the support vector machine and a probabilistic
      neural network. Turn versus non-turn classification was carried out for turn
      families containing intramolecular hydrogen bonds and three to six residues.
      Support vector machine classifiers yielded a Matthews correlation coefficient
      (mcc) of approximately 0.6 and a prediction accuracy of 80%. Probabilistic neural
      networks were developed for beta-turn type prediction. The method was able to
      distinguish between five types of beta-turns yielding mcc > 0.5 and at least 80%
      overall accuracy. We conclude that the proposed new turn classification is
      distinct and well-defined, and machine learning classifiers are suited for
      sequence-based turn prediction. Their potential for sequence-based prediction of
      turn structures is discussed.

PMID- 18618703
TI  - Fine-needle aspiration biopsy of primary osteosarcoma of the thyroid: report of a
      case and review of the literature.
AB  - Primary osteosarcoma of the thyroid is an extremely rare tumor, with only 27 well
      documented cases reported in the literature, including only one in the cytology
      literature. We describe here an additional case with fine-needle aspiration
      biopsy findings. A 60-year-old woman presented with a 1-month history of
      progressive midline neck swelling. CT and ultrasound demonstrated a large thyroid
      mass with tracheal compression. Fine-needle aspiration biopsies were performed
      and showed pleomorphic spindle and epithelioid neoplastic cells, multinucleated
      giant cells, and scant metachromatic extracellular matrix material. Cell block
      sections contained minute tissue fragments with neoplastic spindle cells.
      Immunohistochemical stains showed the tumor cells to be positive for vimentin and
      negative for cytokeratins, TTF-1, calcitonin, synatophysin, chromogranin, and S
      100 protein, suggesting a sarcoma; however, the differential diagnosis also
      included anaplastic thyroid carcinoma and medullary thyroid carcinoma. Tissue
      biopsy revealed a high-grade spindle cell neoplasm with osteoid production,
      consistent with osteosarcoma of the thyroid. The patient developed a large
      pulmonary embolus and superior vena cava syndrome and no further surgical
      intervention was performed. She died 5 weeks after the initial diagnosis. Upon
      retrospective review, the cytologic features resemble osteosarcoma in other
      areas. Although cytologic features on fine-needle aspiration biopsy may suggest a
      diagnosis of this rare entity, definitive diagnosis should be deferred to
      histologic examination.

PMID- 18618704
TI  - Cytomorphology of lymphoepithelioma-like carcinoma of the urinary bladder: report
      of two cases.
AB  - Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is a rare variant
      of high-grade urothelial carcinoma. Here, we report urine cytologic findings in
      two cases of this rare entity, the diagnosis of which was confirmed by
      histopathological examination of the resected tumors. The cytomorphologic
      features included large tumor cells with high nuclear to cytoplasmic ratios,
      vesicular chromatin, and prominent nucleoli, presented as single cells or
      intermixed with inflammatory cells. The differential diagnosis included otherwise
      typical high-grade urothelial carcinoma, reactive urothelial cells and rarely
      large cell lymphoma. The rarity of the tumor cells may impose a diagnostic
      challenge in urine specimen.

PMID- 18618705
TI  - Energetics of the loop-to-helix transition leading to the coiled-coil structure
      of influenza virus hemagglutinin HA2 subunits.
AB  - Fusion of influenza virus with the endosomal membrane of the host cell is
      mediated by the homotrimer-organized glycoprotein hemagglutinin (HA). Its fusion
      activity is triggered by a low pH-mediated conformational change affecting the
      structure of the HA1 and HA2 subunits. The HA2 subunits undergo a loop-to-helix
      transition leading to a coiled-coil structure, a highly conserved motif for many
      fusion mediating viral proteins. However, experimental studies showed that the
      HA2 coiled-coil structure is stable at neutral and low pH, implying that there is
      no direct relationship between low pH and the HA2 loop-to-helix transition. To
      interpret this observation, we used a computational approach based on the
      dielectric continuum solvent model to explore the influence of water and pH on
      the free energy change of the transition. The computations showed that the
      electrostatic interaction between HA2 fragments and water is the major driving
      force of the HA2 loop-to-helix transition leading to the coiled-coil structure,
      as long as the HA1 globular domain covering the HA2 subunits in the nonfusion
      competent conformation is reorganized and thereby allows water molecules to
      interact with the whole loop segments of the HA2 subunits. Moreover, we show that
      the energy released by the loop-to-helix transition may account for those
      energies required for driving the subsequent steps of membrane fusion. Such a
      water-driven process may resemble a general mechanism for the formation of the
      highly conserved coiled-coil motif of enveloped viruses.

PMID- 18618708
TI  - MADAMM: a multistaged docking with an automated molecular modeling protocol.
AB  - Dealing with receptor flexibility in docking methodology is still a problem. The
      main reason behind this difficulty is the large number of degrees of freedom that
      have to be considered in this kind of calculations. In this paper, we present an
      automated procedure, called MADAMM, that allows flexibilization of both the
      receptor and the ligand during a multistaged docking with an automated molecular
      modeling protocol. We show that the orientation of particular residues at the
      interface between the protein and the ligand have a crucial influence on the way
      they interact during the docking process, and the standard docking methodologies
      failed to predict their correct mode of binding. We present some examples that
      demonstrate the capabilities of this approach when compared with traditional
      docking methodologies.

PMID- 18618707
TI  - The structure of the PP2A regulatory subunit B56 gamma: the remaining piece of
      the PP2A jigsaw puzzle.
AB  - The PP2A serine/threonine phosphatase regulates a plethora of cellular processes.
      In the cell the predominant form of the enzyme is a heterotrimer, formed by a
      core dimer composed of a catalytic and a scaffolding subunit, which assemble
      together with one of a range of different regulatory B subunits. Here, we present
      the first structure of a free non-complexed B subunit, B56 gamma. Comparison with
      the recent structures of a heterotrimeric complex and the core dimer reveals
      several significant conformational changes in the interface region between the
      B56 gamma and the core dimer. These allow for an assembly scheme of the PP2A
      holoenzyme to be put forth where B56 gamma first complexes with the scaffolding
      subunit and subsequently binds to the catalytic subunit and this induces the
      formation of a binding site for the invariant C-terminus of the catalytic subunit
      that locks in the complex as a last step of assembly.

PMID- 18618709
TI  - Crystal structure of a putative DNA methylase TTHA0409 from Thermus thermophilus
      HB8.

PMID- 18618710
TI  - Crystal structure of human phosphomevalonate kinase at 1.8 A resolution.

PMID- 18618711
TI  - Computational protein design with side-chain conformational entropy.
AB  - Recent advances in modeling protein structures at the atomic level have made it
      possible to tackle "de novo" computational protein design. Most procedures are
      based on combinatorial optimization using a scoring function that estimates the
      folding free energy of a protein sequence on a given main-chain structure.
      However, the computation of the conformational entropy in the folded state is
      generally an intractable problem, and its contribution to the free energy is not
      properly evaluated. In this article, we propose a new automated protein design
      methodology that incorporates such conformational entropy based on statistical
      mechanics principles. We define the free energy of a protein sequence by the
      corresponding partition function over rotamer states. The free energy is written
      in variational form in a pairwise approximation and minimized using the Belief
      Propagation algorithm. In this way, a free energy is associated to each amino
      acid sequence: we use this insight to rescore the results obtained with a
      standard minimization method, with the energy as the cost function. Then, we set
      up a design method that directly uses the free energy as a cost function in
      combination with a stochastic search in the sequence space. We validate the
      methods on the design of three superficial sites of a small SH3 domain, and then
      apply them to the complete redesign of 27 proteins. Our results indicate that
      accounting for entropic contribution in the score function affects the outcome in
      a highly nontrivial way, and might improve current computational design
      techniques based on protein stability.

PMID- 18618712
TI  - Crystal structure of human carbonic anhydrase XIII and its complex with the
      inhibitor acetazolamide.
AB  - The cytosolic isoform XIII is a recently discovered member of the human carbonic
      anhydrase (hCA, EC 4.2.1.1) family. It is selectively expressed among other
      tissues in the reproductive organs, where it may control pH and ion balance
      regulation, ensuring thus proper fertilization conditions. The authors report
      here the X-ray crystallographic structure of this isozyme in the unbound state
      and in complex with a classical sulfonamide inhibitor, namely acetazolamide. A
      detailed comparison of the obtained structural data with those already reported
      for other CA isozymes provides novel insights into the catalytic properties of
      the members of this protein family. On the basis of the inhibitory properties of
      acetazolamide against various cytosolic/transmembrane isoforms and the structural
      differences detected within the active site of the various CA isoforms, further
      prospects for the design of isozyme-specific CA inhibitors are here proposed.

PMID- 18618713
TI  - Redundant DNA methylation in colorectal cancers of Lynch-syndrome patients.
AB  - Lynch syndrome is an inherited disease resulting predominantly in colorectal
      cancer (CRC). The crucial cause is DNA mismatch repair (MMR) malfunction that is
      associated mostly with MLH1 or MSH2 germline mutations. A significant hallmark of
      repair defects is a high level of instability in microsatellites (MSI-H). In many
      sporadic unstable CRCs, the MLH1 gene is inactivated by promoter hypermethylation
      in addition to extensive promoter methylation in many tumor-suppressor genes
      known as CpG island methylation phenotype (CIMP). To investigate the possible
      role of epigenetic alterations in causing MMR deficiency and thereby Lynch
      syndrome, we evaluated the MLH1 specific and global hypermethylation in
      hereditary CRCs. Of 22 Lynch-syndrome-related CRCs, 18 (81.8%) demonstrated
      various levels of DNA methylation; of these, 14 (63.6%) and 4 (18.2%) were
      methylated in distal and both distal and proximal regions of the MLH1 promoter,
      respectively. However, only 7/18 (38.9%) of results were confirmed by bisulfite
      sequencing. Similar methylation patterns in tumors and frequently in matched
      normal DNA were found in twelve and four patients with MLH1 and MSH2 alterations
      documented by the absence of protein or presence of germline mutation,
      respectively. Moreover, the same results were observed in five stable CRCs. None
      of 22 Lynch-syndrome-related tumors presented CIMP in contrast to 3/10 (30%)
      stable carcinomas. The rather randomly distributed weak methylation patterns in
      hereditary CRCs indicate that epigenetic events are redundant in Lynch-syndrome
      etiology, in contrast to the widespread DNA methylation in sporadic unstable
      CRCs. These methylation-profile differences can lead to more effective molecular
      diagnosis of Lynch syndrome.

PMID- 18618714
TI  - Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute
      lymphocytic leukemia.
AB  - Activating mutations in JAK2 are found in virtually all patients with
      polycythemia vera, and about half of those with essential thrombocythemia and
      primary myelofibrosis. In addition, less common aberrations (particularly gene
      fusions) involving JAK2 have been described in acute leukemias. With the advent
      of JAK2 inhibitor trials in myeloproliferative disorders, tumors with JAK2
      mutations or rearrangements have become candidates for targeted therapy. In this
      report, we identify SSBP2 as a new JAK2 fusion partner in a patient with pre-B
      cell acute lymphocytic leukemia. This finding adds to the expanding compendium of
      JAK2 aberrations found in various hematopoietic malignancies, as well as the
      potential need for a diagnostic FISH analysis in the appropriate clinical
      setting.

PMID- 18618716
TI  - Fine-needle aspiration of metastatic prostatic neuroendocrine carcinomas:
      cytomorphologic and immunophenotypic features.
AB  - Metastatic prostatic carcinoma may, in rare occasions, present as a
      neuroendocrine tumor. Its recognition is crucial to avert a wrongful exclusion of
      prostate as a primary site. We report five cases of metastatic prostatic
      neuroendocrine carcinoma diagnosed by image-guided fine-needle aspiration biopsy.
      The aspirate smears showed loosely cohesive or dyscohesive clusters of tumor
      cells with scanty (three cases) to moderate amount (two cases) of cytoplasm,
      speckled or coarse chromatin and inconspicuous nucleoli. Nuclear molding and
      necrosis were focally present in two cases. Immunohistochemically, the tumor
      cells were positive for synaptophysin or/and chromogranin, but negative for
      prostatic specific antigen and prostatic specific acid phosphatase. Review of
      prior prostate biopsies/resections revealed adenocarcinoma with focal
      neuroendocrine differentiation in all cases, with two cases being newly
      recognized on retrospective review. Confirming neuroendocrine differentiation in
      the prior biopsy/resection may help to establish a link between metastasis and
      prostate primary.

PMID- 18618715
TI  - Integrated genomic and transcriptional profiling identifies chromosomal loci with
      altered gene expression in cervical cancer.
AB  - For a better understanding of the consequences of recurrent chromosomal
      alterations in cervical carcinomas, we integrated genome-wide chromosomal and
      transcriptional profiles of 10 squamous cell carcinomas (SCCs), 5 adenocarcinomas
      (AdCAs) and 6 normal controls. Previous genomic profiling showed that gains at
      chromosome arms 1q, 3q, and 20q as well as losses at 8q, 10q, 11q, and 13q were
      common in cervical carcinomas. Altered regions spanned multiple megabases, and
      the extent to which expression of genes located there is affected remains
      unclear. Expression analysis of these previously chromosomally profiled
      carcinomas yielded 83 genes with significantly differential expression between
      carcinomas and normal epithelium. Application of differential gene locus mapping
      (DIGMAP) analysis and the array CGH expression integration tool (ACE-it)
      identified hotspots within large chromosomal alterations in which gene expression
      was altered as well. Chromosomal gains of the long arms of chromosome 1, 3, and
      20 resulted in increased expression of genes located at 1q32.1-32.2, 3q13.32-23,
      3q26.32-27.3, and 20q11.21-13.33, whereas a chromosomal loss of 11q22.3-25 was
      related to decreased expression of genes located in this region. Overexpression
      of DTX3L, PIK3R4, ATP2C1, and SLC25A36, all located at 3q21.1-23 and identified
      by DIGMAP, ACE-it or both, was confirmed in an independent validation sample set
      consisting of 12 SCCs and 13 normal ectocervical samples. In conclusion,
      integrated chromosomal and transcriptional profiling identified chromosomal
      hotspots at 1q, 3q, 11q, and 20q with altered gene expression within large
      commonly altered chromosomal regions in cervical cancer.

PMID- 18618717
TI  - Comparison of PAX-2, RCC antigen, and antiphosphorylated H2AX antibody (gamma
      H2AX) in diagnosing metastatic renal cell carcinoma by fine-needle aspiration.
AB  - Diagnosing metastatic renal cell carcinoma (RCC) by fine-needle aspiration (FNA)
      can be challenging. Existing antibodies supporting a diagnosis of RCC, including
      CD10 and RCC-Ma, have problems with specificity and interpretation. In this
      report, we evaluate the use of two newer immunostains, PAX-2 and gamma-H2AX,
      which to our knowledge have not been studied in FNA material, in the diagnosis of
      metastatic RCC and in comparison with RCC-Ma. 29 cases of metastatic RCC were
      identified as well as a TMA of an additional 30 RCC cases. In the case cohort,
      RCC-Ma in a membranous pattern of staining identified 15/27 (56%) metastatic RCC,
      although interpretation was made difficult in many cases due to focality of
      staining and non-specific cytoplasmic staining. PAX-2 stained 23/29 (79%) of
      tumors in a nuclear stain, most strongly. Gamma-H2AX stained 19/26 (73%) of
      metastatic RCC strongly in a nuclear stain. In the TMA, strong, diffuse nuclear
      staining with gamma-H2AX was present in 22/30 RCC (73%). If weak staining was
      also included as positive, 26/30 (87%) were positive. PAX-2 stained RCC TMA with
      a lower percentage at 56%, including weaker staining intensity. Both PAX-2 and
      gamma-H2AX demonstrated patchy staining of normal renal tubules, PAX-2 to a
      greater extent. Both PAX-2 and gamma-H2AX are sensitive markers for the diagnosis
      of metastatic RCC, with improved ease of interpretation when compared with RCC
      Ma. A combination of all 3 markers identified 87% of cases, and failure to stain
      for both PAX-2 and gamma-H2AX suggests against, but does not disprove, a
      diagnosis of RCC.

PMID- 18618718
TI  - Volvox species in the Pap test of a 24-year-old female.

PMID- 18618719
TI  - In vivo evaluation of biodegradable magnesium alloy bone implant in the first 6
      months implantation.
AB  - In vivo degradation of magnesium alloy implant, the bone response to the
      magnesium, and the effect of the degradation of magnesium on the blood
      composition and organs were investigated by using light microscopy and scanning
      electronic microscopy with energy dispersive spectrum. Magnesium alloy showed
      different degradation rates in the marrow channel and the cortical bone. More
      degradation of magnesium implant was observed in the marrow channel than in the
      cortical bone. New bone tissue formed around the magnesium implants after 6 weeks
      implantation but no fibrous capsule was found. There existed two distinct layers
      separating the new bone tissue from the magnesium implant. On the magnesium
      implant side, crystalline magnesium calcium phosphate formed on the surface of
      the implant due to the reaction between the implant and blood or body fluid. On
      the new bone tissue side was a 10-30-microm membrane comprising two distinct
      layers with many fibroblasts in the layer close to the new bone tissue. The new
      bone was in tight contact with the implant through the membrane and phosphate
      layer due to the good osteoconductivity of the phosphate layer. After 10 and 26
      weeks postimplantation, more new bone tissues as well as the membrane were found
      around the implant. However, no apparent increase in the thickness of the
      membrane was observed with the increasing of the implantation duration. Blood
      examination has shown that the degradation of the magnesium implant caused little
      change to blood composition but no disorder to liver or kidneys.

PMID- 18618720
TI  - HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of
      papillary thyroid carcinoma.
AB  - The cytologic diagnosis of papillary thyroid carcinoma is straightforward in most
      instances. However, there are some mimics including goitrous nodules and Hurthle
      cell neoplasms. Many studies have shown the combination of HBME-1 and CK19
      expression to be useful in reaching a correct histologic diagnosis on tissue
      sections. We aim to assess the value of these markers in the setting of cell
      blocks prepared from needle aspiration specimens. We performed
      immunohistochemical staining of HBME-1 and CK19 on cell block material from 22
      thyroid nodules that also had follow-up histology. Both CK19 and HBME-1 were
      strongly positive in all nine cases of papillary thyroid carcinoma, the latter
      showing distinct luminal accentuation. In the non-papillary carcinomas, none
      showed positivity for both HBME-1 and CK19. Two of six Hurthle cell neoplasms
      were positive for CK19, however all were negative for HBME-1. One of nine
      goitrous nodules was strongly positive for HBME-1 with luminal/membranous
      staining, but this were negative for CK19. The sensitivity, specificity and
      positive predictive value of HBME-1 in distinguishing between papillary thyroid
      carcinoma and goitrous nodules/Hurthle cell neoplasms were found to be 100%,
      92.9% and 0.9, respectively; and that of HBME-1 and CK19 combination was 100%,
      100% and 1. We thus conclude that the combination of positive HBME-1
      (luminal/membranous) and CK 19 (cytoplasmic) staining on cell blocks of thyroid
      cytologic specimens is highly discriminatory in the diagnostic workup for
      papillary thyroid carcinoma.

PMID- 18618721
TI  - Flower-like colloid on thyroid fine needle aspiration.

PMID- 18618722
TI  - From the 19th century to the 21st, an old dilemma: ciliocytophthoria,
      multiflagellated protozoa, or both?

PMID- 18618723
TI  - Paracoccidioides brasiliensis in a liquid-based Papanicolaou test from a pregnant
      woman: report of a case.
AB  - With the exception of Candida species, fungal organisms are rarely encountered in
      the Papanicolaou test and, when encountered, usually represent contaminants
      rather then infections. We present the case of a healthy 29-year-old pregnant
      female, gravida 1, para 0, who presented for her first prenatal visit at 12-week
      gestation and had many large fungal-like elements with a distinct budding pattern
      of multiple narrow-based buds resembling a "ship's-wheel" identified in her
      routine liquid-based Papanicolaou test. Based on its characteristic appearance in
      the Papanicolaou test and the hematoxylin and eosin, periodic acid Schiff and
      Gomori's methenamine silver stains performed on the cell block made from the
      residual sample, the fungus was diagnosed as "consistent with Paracoccidioides."
      This is the second reported case of Paracoccidioides presenting in a Papanicolaou
      test and shows that this organism may rarely involve the uterine cervix in the
      absence of clinical systemic disease.

PMID- 18618724
TI  - KOC (K homology domain containing protein overexpressed in cancer) and S100A4
      protein immunoreactivity improves the diagnostic sensitivity of biliary brushing
      cytology for diagnosing pancreaticobiliary malignancies.
AB  - Biliary tract brush cytology is one of the favored methods of evaluating lesions
      of the pancreatobiliary tract. However, although its specificity has been
      reported to be high (91-100%), the sensitivity is lower (30-88%). In this study
      we applied KOC and S100A4 protein immunocytochemistry to assess their potential
      use as adjunct markers in differentiating benign from malignant cells, and
      improve the diagnostic sensitivity of this method for pancreatobiliary
      malignancies. The authors examined KOC and S100A4 protein expression in 44
      alcohol-fixed cytology specimens obtained by biliary brushings. Diagnoses
      included: (1) benign/atypical favor reactive (20 cases), (2) atypical/not
      diagnostic of malignancy (3 cases), and (3) suspicious for malignancy/malignant
      (21 cases). Alcohol-fixed Papanicolaou-stained slides (PAP) were stained with
      monoclonal antibody to KOC/L523S and polyclonal antibody to S100A4 protein.
      Results were recorded as negative or positive. Twenty-four cases were confirmed
      positive for adenocarcinoma and 20 cases were negative. The sensitivity and
      specificity of cytology was 83 and 95%, KOC showed a sensitivity of 92% and
      specificity of 95%. S100A4 protein showed a sensitivity of 79% and a specificity
      of 95%. The combined use of KOC and S100A4 protein showed a sensitivity of 100%
      and a specificity of 95%, respectively. The concurrent use of KOC and S100A4
      protein improves the diagnostic sensitivity of biliary brushings cytology and
      demonstrates similar specificity as cytology alone in the diagnosis of
      pancreatobiliary malignancy.

PMID- 18618725
TI  - Cytological features of myxoid adrenocortical adenoma with a pseudoglandular
      component: a case report with differential diagnostic considerations.
AB  - Myxoid adrenocortical tumors are extremely rare neoplasms with only nine adenomas
      and eleven carcinomas reported in the literature. They occasionally have a
      pseudoglandular component resembling metastatic mucinous adenocarcinoma in the
      adrenal gland. However the cytological features of this unusual tumor have not
      been previously described. We report here the first cytopathological study of a
      myxoid adrenocortical adenoma with a pseudoglandular component, contributing
      especially to the differential diagnosis from metastatic mucinous adenocarcinoma.
      Two major cytopathological features distinguishing myxoid adrenocortical adenoma
      from metastatic mucinous adenocarcinoma in the adrenal gland are: (1) the myxoid
      material is found only in the extracellular space, and not in the cytoplasm; and
      (2) nuclei are usually located in the central portion of the cytoplasm, and not
      compressed to the periphery. Careful observation of these cytological features
      and positive immunoreactivity to Melan A, alpha-inhibin and synaptophysin can
      lead to the correct diagnosis.

PMID- 18618726
TI  - Fine-needle aspiration cytology of pulmonary mucinous cystadenocarcinoma.
AB  - A 64-year-old man presented with symptoms of a lung infection. Radiologic work-up
      revealed opacity in the upper lobe of right lung. A computer tomographic (CT)
      guided fine-needle aspiration biopsy revealed sheets and clusters of mild to
      moderately atypical epithelial cells, small amount of mucin, histiocytes,
      multinucleated giant cells, and stromal fragments. The differential diagnosis
      included an inflammatory process and a well-differentiated adenocarcinoma. A
      lobectomy was performed and revealed abundant extracellular mucin surrounded
      partially by a thick fibrous wall, which was lined by neoplastic glandular cells.
      The histology was consistent with a pulmonary mucinous cystadenocarcinoma.
      Fibroblastic proliferation and foreign-body giant reaction secondary to
      extravasation of mucin were also noted. The patient was disease free 1 year after
      initial diagnosis. The relative lack of mucin as well as the presence of well
      differentiated neoplastic cells, the inflammatory response to extravasated mcuin
      constitutes a potential pitfall in recognizing pulmonary mucinous
      cystadenocarcinoma cytologically.

PMID- 18618727
TI  - WCAFTI: worrisome cytologic alterations following tissue infarction; a mimicker
      of malignancy in breast cytology.
AB  - The acronym WCAFTI (cafti)-(Worrisome cytologic alterations following tissue
      infarction) is introduced here for the first time for the entity which describes
      the spectrum of cytologic changes seen in spontaneous infarction of an epithelial
      lesion. The pathology may be responsible for abnormal cytologic findings such as
      cellular dyshesiveness, nuclear enlargement with cytoplasmic blurring and
      irregular nuclei. Although, it is a rare event, it is essential for a cytologist
      to be aware of this new acronym WCAFTI to avoid misinterpretation of atypical
      cells and necrosis as indicators of malignancy. It is typically described here in
      a fibroadenoma from a 49-year-old female who sought medical help for pain in left
      breast mass.

PMID- 18618728
TI  - Imprint cytology of high-grade immature ovarian teratoma: a case report,
      literature review, and distinction from other ovarian small round cell tumors.
AB  - Immature ovarian teratoma (IOT) is a rare and aggressive malignant neoplasm
      characterized by immature neural tissue. The cytomorphologic features have only
      rarely been described. We herein describe an additional case and review the
      literature regarding this entity. To the best of our knowledge, this is the first
      reported case with imprint cytology. A 35-year-old woman presented with a pelvic
      mass which was resected and sent for frozen section evaluation. Imprint smears
      and frozen section of the mass were diagnostic of IOT. IOT has diagnostic
      cytologic features which show complete concordance with histology. Differential
      diagnoses include other small round cell neoplasms such as ovarian neuroblastoma,
      small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor,
      Wilm's tumor, desmoplastic small round cell tumor, and Non-Hodgkin lymphoma.
      Distinguishing IOT from these tumors can be challenging however if diligent
      morphologic study and/or ancillary studies are performed accurate diagnosis is
      possible.

PMID- 18618729
TI  - Aspiration cytodiagnosis of an endodermal cyst located at L1/L2 region of spinal
      canal.

PMID- 18618730
TI  - Intranuclear cytoplasmic inclusion is a significant diagnostic feature for the
      differentiation of lobular endocervical glandular hyperplasia from minimal
      deviation adenocarcinoma of the cervix.
AB  - Lobular endocervical glandular hyperplasia (LEGH) is a cervical lesion with
      pyloric gland metaplasia. Minimal deviation adenocarcinoma (MDA) is an extremely
      well differentiated form of endocervical adenocarcinoma (AC). To date, it is
      difficult to differentiate LEGH from MDA because they share similar clinical,
      radiological, and immunohistochemical features. Furthermore, the cytological
      features of LEGH and MDA have not been well defined. In the present study, we
      describe the cytological features of LEGH and MDA. We reviewed 24 cases of LEGH
      (18 pure and six mixed forms) and four MDA cases of the cervix. A total of 40
      cytologic smears from 28 patients were reviewed. Abundant yellow mucin was
      frequently present in both LEGH and MDA; however, an INCI was found in 22 of the
      24 LEGH cases and it was not found in either MDA or adenocarcinoma cells
      associated with LEGH. Neither cell atypia nor architectural distortion was
      observed in LEGH. In MDA, slight cellular atypia, three dimensional, irregular
      cell clustering, and prominent nucleoli were observed. The presence of an INCI is
      a good parameter for the diagnosis of LEGH. Cytology is an effective aid in the
      differentiation of LEGH from MDA.

PMID- 18618732
TI  - Distribution of Y chromosomes among native North Americans: a study of Athapaskan
      population history.
AB  - In this study, 231 Y chromosomes from 12 populations were typed for four
      diagnostic single nucleotide polymorphisms (SNPs) to determine haplogroup
      membership and 43 Y chromosomes from three of these populations were typed for
      eight short tandem repeats (STRs) to determine haplotypes. These data were
      combined with previously published data, amounting to 724 Y chromosomes from 26
      populations in North America, and analyzed to investigate the geographic
      distribution of Y chromosomes among native North Americans and to test the
      Southern Athapaskan migration hypothesis. The results suggest that European
      admixture has significantly altered the distribution of Y chromosomes in North
      America and because of this caution should be taken when inferring prehistoric
      population events in North America using Y chromosome data alone. However,
      consistent with studies of other genetic systems, we are still able to identify
      close relationships among Y chromosomes in Athapaskans from the Subarctic and the
      Southwest, suggesting that a small number of proto-Apachean migrants from the
      Subarctic founded the Southwest Athapaskan populations.

PMID- 18618731
TI  - Identifying functional neighborhoods within the cell nucleus: proximity analysis
      of early S-phase replicating chromatin domains to sites of transcription, RNA
      polymerase II, HP1gamma, matrin 3 and SAF-A.
AB  - Higher order chromatin organization in concert with epigenetic regulation is a
      key process that determines gene expression at the global level. The organization
      of dynamic chromatin domains and their associated protein factors is intertwined
      with nuclear function to create higher levels of functional zones within the cell
      nucleus. As a step towards elucidating the organization and dynamics of these
      functional zones, we have investigated the spatial proximities among a
      constellation of functionally related sites that are found within euchromatic
      regions of the cell nucleus including: HP1gamma, nascent transcript sites (TS),
      active DNA replicating sites in early S-phase (PCNA) and RNA polymerase II sites.
      We report close associations among these different sites with proximity values
      specific for each combination. Analysis of matrin 3 and SAF-A sites demonstrates
      that these nuclear matrix proteins are highly proximal with the functionally
      related sites as well as to each other and display closely aligned and
      overlapping regions following application of the minimal spanning tree (MST)
      algorithm to visualize higher order network-like patterns. Our findings suggest
      that multiple factors within the nuclear microenvironment collectively form
      higher order combinatorial arrays of function. We propose a model for the
      organization of these functional neighborhoods which takes into account the
      proximity values of the individual sites and their spatial organization within
      the nuclear architecture.

PMID- 18618733
TI  - Real time noninvasive monitoring of contaminating bacteria in a soft tissue
      implant infection model.
AB  - Infection is the main cause of biomaterials-related failure. A simple technique
      to test in-vivo new antimicrobial and/or nonadhesive implant coatings is
      unavailable. Current in vitro methods for studying bacterial adhesion and growth
      on biomaterial surfaces lack the influence of the host immune system. Most in
      vivo methods to study biomaterials-related infections routinely involve implant
      removal, preventing comprehensive longitudinal monitoring. In vivo imaging
      circumvents these drawbacks and is based on the use of noninvasive optical
      imaging of bioluminescent bacteria. Staphylococcus aureus Xen29 is genetically
      modified to be stably bioluminescent, by the introduction of a modified full lux
      operon onto its chromosome. Surgical meshes with adhering S. aureus Xen29 were
      implanted in mice and bacterial growth and spread into the surrounding tissue was
      monitored longitudinally from bioluminescence with a highly sensitive CCD camera.
      Distinct spatiotemporal bioluminescence patterns, extending beyond the mesh area
      into surrounding tissues were observed. After 10 days, the number of living
      organisms isolated from explanted meshes was found to correlate with
      bioluminescence prior to sacrifice of the animals. Therefore, it is concluded
      that in vivo imaging using bioluminescent bacteria is ideally suited to study
      antimicrobial coatings taking into account the host immune system. In addition,
      longitudinal monitoring of infection in one animal will significantly reduce the
      number of experiments and animals.

PMID- 18618734
TI  - An abductive perspective on clinical reasoning and case formulation.
AB  - Clinical reasoning has traditionally been understood in terms of either
      hypothetico-deductive or Bayesian methods. However, clinical psychology requires
      an organizing framework that goes beyond the limits of these methods and
      characterizes the full range of reasoning processes involved in the description,
      understanding, and formulation of the difficulties presented by clients. In this
      article, the authors present a framework for clinical reasoning and case
      formulation that is largely based on a broad abductive theory of scientific
      method (Haig, 2005b). The abductive theory articulates and combines the processes
      of phenomena detection and theory construction. Both of these processes are
      applied to clinical reasoning and case formulation, and a running case example is
      provided to illustrate the application.

PMID- 18618735
TI  - Abductive inferences to psychological variables: Steiger's question and best
      explanations of psychopathy.
AB  - Abductive inference often involves inference to the best explanation. A focus on
      the bestness of explanations facilitates a comparative analysis of how abductive
      inference would differ if approached with four contrasting sets of assumptions
      about how scientific inference works: positivism, realism, and two kinds of
      pragmatism. As a thought experiment, one can imagine a situation in which
      competing models of psychopathy differ in parsimony and fit to the data, but
      produce a tie when considering both virtues in combination. The thought
      experiment demonstrates that Steiger's (1990) question about how best to combine
      competing virtues in scientific inference applies to abductive inference and that
      the answers depend upon other assumptions about how science works. The
      comparative analysis helps focus some of the issues that require clarification
      before abductive inference can enter the Pantheon of standard research methods in
      psychology. More constructively, the analysis also demonstrates that one need not
      accept scientific realism to accept and use abductive inference.

PMID- 18618736
TI  - Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and
      risk of benign prostate hyperplasia in the prostate cancer prevention trial.
AB  - BACKGROUND: We investigated whether peptides involved in cellular proliferation
      and apoptosis, [insulin-like growth factor I (IGFI) and its major binding protein
      (insulin-like growth factor binding protein 3)], predicted risk of benign
      prostate hyperplasia (BPH). METHODS: We conducted a nested-case-control study in
      the placebo arm of the prostate cancer prevention trial (PCPT). Cases (n = 727)
      were men with surgical or medical treatment for BPH; two or more IPSS scores >14;
      or two scores of at least five points over baseline one of which was >or=12.
      Controls (n = 727) were frequency matched by age to cases, reported no BPH
      treatment, and no IPSS score >8. Cases and controls remained on the PCPT placebo
      and were followed closely until their 7-year PCPT anniversary. Baseline serum was
      analyzed for IGFI and IGFBP3. Unconditional logistic regression and polytomous
      regression estimated the multivariate-adjusted odds ratio (OR) for BPH risk.
      RESULTS: IGFBP3 was inversely and the IGFI:IGFBP3 ratio was positively associated
      with BPH risk, but findings were statistically significant only for men with
      severe symptoms (OR = 0.60, 95% CI = 0.40-0.90 for the fifth vs. first quintile
      of IGFBP3, P-trend = 0.01). Associations did not differ by age (<65 or >or=65
      years), and there was a suggestion that the IGFI:IGFBP3 - BPH risk association
      may be stronger among overweight men. CONCLUSIONS: A high IGFI:IGFBP3 ratio was
      associated with increased BPH risk, and high serum IGFBP3 was associated with
      decreased BPH risk among men with severe symptoms. These results confirm findings
      from other recent studies.

PMID- 18618738
TI  - Phase II study of fulvestrant (Faslodex) in castration resistant prostate cancer.
AB  - BACKGROUND: Preclinical evidence supports the role of estrogen receptor signaling
      in prostate cancer. In this trial we investigated the tolerability and efficacy
      of fulvestrant, a pure estrogen receptor antagonist, in the treatment of
      castration resistant prostate cancer (CRPC). METHODS: Patients with CRPC were
      enrolled after written informed consent. Fulvestrant was administered by
      intramuscular injection at a dose of 500 mg on day 0, then 250 mg on day 14, day
      28 and monthly thereafter. History, physical examination, serum prostate specific
      antigen (PSA) levels and toxicity was evaluated monthly. Radiographic studies
      were repeated every 3 months to assess disease. Treatment was continued until
      disease progression, unacceptable toxicity, non-compliance or consent withdrawal.
      RESULTS: Twenty patients were enrolled over a period of six months. All patients
      were Caucasians with median age of 69.5 years [range: 47-85 years]. Sixteen
      patients (80%) had radiological evidence of metastasis and four patients (20%)
      had rising PSA as the only evidence of progressive disease. Patients received a
      median of three treatment cycles of fulvestrant [range: 1-11]. Median time to
      progression was 4.3 months (95% confidence interval of 3-5.7 months) and median
      overall survival was 19.4 months (range: 9.9-19.4 months) after a median follow
      up of 16 months. No patient showed >or=50% reduction in PSA or radiologic
      improvement. Few adverse events were noted, none of which were attributed
      directly to fulvestrant. CONCLUSION: Fulvestrant was well tolerated but failed to
      produce clinical or PSA response in men with CRPC.

PMID- 18618737
TI  - Imatinib mesylate in combination with docetaxel for the treatment of patients
      with advanced, platinum-resistant ovarian cancer and primary peritoneal
      carcinomatosis : a Hoosier Oncology Group trial.
AB  - BACKGROUND: Ovarian tumors frequently express c-Kit and/or platelet-derived
      growth factor receptors (PDGFRs). Imatinib mesylate blocks the growth of ovarian
      cancer cells in vitro and may enhance the activity of chemotherapy. This study
      was conducted to determine the activity of imatinib in combination with docetaxel
      in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC).
      METHODS: Eligible patients had recurrent, platinum-resistant, or refractory EOC
      that expressed PDGFRalpha or c-kit, as determined by immunohistochemistry.
      Imatinib mesylate at a dose of 600 mg orally once daily was administered
      continuously with docetaxel at a dose of 30 mg/m(2) given intravenously once
      weekly in Weeks 1 through 4 of every 6-week cycle. The primary endpoint was
      objective response rate (ORR) as assessed by the Response Evaluation Criteria in
      Solid Tumors (RECIST). RESULTS: Thirty-four patients were screened for PDGFRalpha
      and c-kit expression to enroll 23 patients between December 2003 and October
      2005. Four patients had c-kit-positive/PDGFR-negative tumors, 11 patients had
      PDGFR-positive/c-kit-negative tumors, and 8 patients had c-kit-positive/PDGFR
      positive tumors. The median patient age was 56 years (range, 33-76 years).
      Patients had received a median of 3 prior treatments. The ORR was 21.7% and
      included 1 complete and 4 partial responses. An additional 3 patients had stable
      disease for more than 4 months. Expression of PDGFR, c-kit, phosphatase and
      tensin homolog (PTEN), and phosphorylated protein kinase B (Akt) did not predict
      response to therapy. The most common adverse events encountered were fatigue
      (83%), nausea (74%), diarrhea (61%), anorexia (52%), and edema (65%), and the
      majority of those events were graded as grade 1 or 2. CONCLUSIONS: The
      combination imatinib and docetaxel was tolerated in patients with heavily
      pretreated EOC that expressed c-kit or PDGFRalpha. Few patients had sustained
      responses or stable disease.

PMID- 18618739
TI  - Molecular characterization of nitrite reductase gene (aniA) and gene product in
      Neisseria meningitidis isolates: is aniA essential for meningococcal survival?
AB  - The present study evaluates sequence conservation in the gene coding for nitrite
      reductase (aniA) and AniA expression from a panel of Neisseria meningitidis
      isolates. Sequence analysis of the coding region in 19 disease-associated and 4
      carrier strains notwithstanding a high degree of sequence similarity showed a
      number of nucleotide changes, some of which possibly resulted in premature
      translation termination or function loss. In particular, in one disease
      associated strain a 9-residues insertion was found to be located close to the
      type I Cu-site and a catalytic histidine at position 280 was mutated into a
      leucine. In two strains from carriers, a sequence corresponding to a portion of a
      transposase gene within the aniA was also found. The AniA protein was always
      expressed, except for these two carriers strains and for other two strains in
      which the presence of the premature stop codons was recognized. The biochemical
      properties of the cloned soluble domain of the enzyme (sAniA) from N.
      meningitidis reference MC58 strain and from a clinical invasive isolate were
      studied. In particular, biochemical analysis of sAniA from MC58 demonstrated a
      clear dependence of its catalytic activity upon acidification, while the clinical
      isolate-derived sAniA was not functional. Thus, the results obtained suggest that
      the presence of a conserved and functional aniA gene is not essential for
      meningococcal survival.

PMID- 18618741
TI  - Kinetic investigation of microbial souring in porous media using microbial
      consortia from oil reservoirs.
AB  - Microbial souring (H2S production) in porous media was investigated in an
      anaerobic upflow porous media reactor at 60 degrees C using microbial consortia
      obtained from oil reservoirs. Multiple carbon sources (formate, acetate,
      propionate, iso- and n-butyrates) found in reservoir waters as well as sulfate as
      the electron acceptor was used. Kinetics and rates of souring in the reactor
      system were analyzed. Higher volumetric substrate consumption rates (organic
      acids and sulfate) and a higher volumetric H(2)S production rate were found at
      the from part of the reactor column after H(2)S production had stabilized.
      Concentration gradients for the substrates (organic acids and sulfate) and H(2)S
      were generated along the column. Biomass accumulation throughout the entire
      column was observed. The average specific sulfate reduction rate (H(2)S
      production rate) in the present reactor after H(2)S production had stabilized was
      calculated to be 11062 +/-2.22 mg sulfate-S/day g biomass.

PMID- 18618742
TI  - Microfiltration of streptococcal fermentation broths: study of the factors
      affecting the concentration effect.
AB  - Streptokinase (SK) recovery from streptococcal fermentation broth by cross-flow
      microfiltration has been studied. Recovery of SK in the filtrate, independent of
      the volumetric concentration factor, is approximately two-fold lower than the
      initial SK activity in the fermentation broth; moreover, the SK activity in the
      retentate increase during the process, reaching a concentration factor of 2.73.
      These results show that the membrane works more as an ultrafiltration membrane,
      with rejection of S = 0.6, than as a microfiltration membrane. Under filtration
      conditions, the membrane permeation rate decreased with time. This decreased
      could be explained by deposition and interaction of material onto/with the
      membrane resulting in the concentration of permeable products. Studies of the
      individual concentration factors for the main streptococcal exocellular proteins,
      indicate clearly that the concentration of the proteins during the
      microfiltration process is independent of the size of the proteins, suggesting
      that other factors, such as charge and hydrophobicity, along with concentration
      polarization, should be taken also into account for the understanding of this
      phenomenon.

PMID- 18618743
TI  - Equilibrium and kinetic studies on reversible and irreversible denaturation of
      micrococcal nuclease.
AB  - The effect of pH and temperature on the thermal denaturation of micrococcal
      nuclease were investigated. The ranges employed were between pH3.30 and pH9.70
      and between 10 degrees C and 85 degrees C, respectively. The reversible
      denaturation involved in the whole process was clearly discriminated from the
      irreversible one. The former took place with a large enthalpy change of 384 kJ
      mol(-1) at pH 9.70, where the enzyme exhibited it s maximum activity. The latter
      probably led to aggregation because the successive long incubation after complete
      deactivation caused precipitation. A reasonable scheme explaining the process
      involving both denaturations was proposed and the kinetic on the irreversible
      deactivation was performed. It was revealed that the irreversible deactivation
      involved two types of reactions whose activation energies were relatively small:
      22.2 kJ mol(-1) and 18.8 kJ mol(-1). The presence of sucrose suppressed the
      reversible denaturation without significant influence on enthalpy change, whereas
      it affected little the irreversible deactivation kinetically. The effects of pH
      change and addition of sucrose on the denaturation were discussed
      thermodynamically, especially in terms of the entropy change.

PMID- 18618744
TI  - Cyclic AMP regulation of tylosin biosynthesis and secondary metabolism in
      Streptomyces fradiae.
AB  - Adenosine 3':5' cyclic monophosphate seems to regulate antibiotic biosynthesis
      and secondary metabolism in tylosin-producing cultures of Streptomyces fradiae
      C373.1. A dose-dependent response is observed by exogenous additions of dibutyryl
      cyclic AMP (cAMP), and is related to the nutritional status of the culture.
      Addition of cAMP to cultures growing in nutritionally lean media caused higher
      cumulative antibiotic tigers and some cellular differentiation compared with the
      control. In nutritionally rich media, a qualitatively different behavior
      resulted: an almost instantaneous shift toward secondary metabolism occurred. The
      response is characterized by extensive cellular differentiation with little
      growth and only a trace of antibiotic production. The possible role of cyclic AMP
      n the regulation of tylosin biosynthesis and secondary metabolism and its
      relation to specific nutrient limitations in synthetic, defined media in
      Streptomyces fradiae is discussed.

PMID- 18618745
TI  - Application of the transition time of metabolic system as a criterion for
      optimization of metabolic processes.
AB  - Transition time of metabolic systems in introduced as a suitable optimization
      criterion for biotechnological processes in which it is desirable to reduce the
      lag time and minimize the mass contained within the system. Lag time is the time
      needed for the system to attain the steady state. Results obtained from the
      sensitivity analysis of this steady state response are presented within the
      metabolic control analysis and applied to 3 case studies. In all of them the
      information provided by the transition time control profile allows the
      implementation of a strategy for biotechnological manipulations aimed at the
      improvement of the process.

PMID- 18618746
TI  - Chemical and enzymatic extraction of heavy metal binding polymers from isolated
      cell walls of Saccharomyces cerevisiae.
AB  - Isolated cell walls of the yeast Saccharomyces cerevisiae were treated by either
      chemical (alkali and acid) or enzymatic (protease, mannanase or beta
      glucuronidase) processes to yield partially purified products. These products
      were partially characterized by infrared analysis. They were subsequently reacted
      with heavy metal cation solutions and the quantity of metal accumulated by the
      cell wall material determined. The Cu(2+) ion (0.24, 0.36, 1.12, and 0.60
      micromol/mg) was accumulated to a greater extent than either Co(2+) (0.13, 0.32,
      0.43, and 0.32 micromol/mg) or Cd(2+) (0.17, 0.34, 0.39, and 0.32 micromol/mg) by
      yeast cell walls, glucan, mannan, and chitin, respectively The isolated
      components each accumulated greater quantities of the cations than the intact
      cell wall. Removal of the protein component of the yeast cell walls by Pronase
      caused a 29.5% decrease in metal accumulation by yeast cell walls per mass,
      indicating the protein is a heavy metal accumulating component. The data indicate
      that the outer mannan-protein layer of the yeast cell wall is more important than
      the inner glucan-chitin layer in heavy metal action accumulation.

PMID- 18618747
TI  - Transient responses of hybridoma cells in continuous culture to step changes in
      amino acid and vitamin concentrations.
AB  - The effects of step-change increase in the concentrations of amino acids and
      vitamins on the metabolism, growth, and antibody productivity of a murine
      hybridoma cell line grown in continuous culture on serum-free medium are
      presented. Additions of the amino acids cysteine with methionine, tryptophan, and
      isoleucine with valine and vitamin B(12) (as cyanocobalamin) resulted in
      significant increases in viable cell concentrations. Additions of aspartate with
      asparagine, and threonine with vitamin B(1) (as thiamine hydrochloride) resulted
      in significant increases in final antibody concentrations. Substantial decrease
      in the fraction of amino acid nitrogen excreted as ammonia occurred upon
      supplementation with three times the normal concentrations of branched chain
      amino acids. Decreases in the fraction of amino acid nitrogen converted to
      ammonia were paralleled by increases in the fraction converted to alanine.

PMID- 18618748
TI  - Monitoring of ethanol during fermentation of a lignocellulose hydrolysate by on
      line microdialysis sampling, column liquid chromatography, and an alcohol
      biosensor.
AB  - During a 70-h fermentation of a lignocellulose hydrolysate, the ethanol produced
      was monitored on-line using a microdialysis probe as an in situ sampling device.
      The dialysate components were then separated in a column liquid chromatographic
      system and the ethanol was selectively detected by an amperometric alcohol
      biosensor. The result was compared with two off-line analysis methods: one
      chromatographic method with refractive index (RI) detection and one enzymatic
      method based on spectrophotometric detection. The two methods base on enzymes
      were shown to give lower values than the chromatographic method based on RI
      detection, which is discussed n terms of selectivity. The investigated on-line
      setup was found to be a flexible system for monitoring of fermentations, allowing
      a sampling frequency of at least 12 h(-1) and with a delay between sampling and
      detection of less than 5 min.

PMID- 18618749
TI  - Effects of medium carbon-to-nitrogen ratio on biofilm formation and plasmid
      stability.
AB  - Biofilm formation and plasmid segregational instability in biofilm cultures of
      Escherichia coli DH5alpha (pMJR1750) were investigated under different medium
      carbon-to-nitrogen (C/N) ratios. At C/N ratios of 0.07 and 1, net accumulation of
      both biofilm plasmid-bearing and plasmid-free cells continued through the entire
      experiment without attaining any apparent steady state. At C/N ratios of 5 and
      10, net biofilm cell accumulation for the two populations reached apparent steady
      states after 84 and 72 h, respectively. At C/N ratios of 0.07 and 1,
      polysaccharide production increased slowly and reached about 2g alginate
      equivalent/cm(2) by the end of both experiments. At a C/N ratio of 5,
      polysaccharide increase significantly after 84 h, reaching about 7 microg
      alginate equivalent/cm(2) prior to termination. At a C/N ratio of 10,
      polysaccharide increased significantly after 72 h and reached 21 microg alginate
      equivalent/cm(2) at 108 h. At C/N ratios of 0.07 and 1, protein production
      reached 6.5 and 4 microg/cm(2), respectively. At C/N ratios of 5 and 10, protein
      production increased slightly for the first 84 h and reached a maximum at 108 h,
      at 3 and 2 microg/cm(2), respectively, then decreased over the last 12 h of the
      experiment. Ratios of polysaccharide to protein increased with increasing C/N
      ratios. At C/N ratios of 0.07 and 1, the ratios between extracellular
      polysaccharide (EP) and protein were no more than 205 microg
      polysaccharide/microg protein, whereas those at C/N ratios of 5 and 10 increased
      to about 7 and 12 microg polysaccharide/microg protein,
      respectively.Probabilities of plasmid loss in the biofilm cultures increased with
      increasing C/N ratios. At C/N ratios of 0.07, 1, and 5, the probabilities of
      plasmid loss were 0.0013 +/- 0.011, 0.020 +/- 0.006 and 0.122 +/- 0.021,
      respectively. At a C/N ratio of 10, the probability of plasmid loss was
      significantly higher, reaching 0.38 +/- 0.125. The increase of probability of
      plasmid loss at higher C/N ratios results from competition between cell
      replication and extracellular polysaccharide production.

PMID- 18618750
TI  - Peptide synthesis with a proteinase from the extremely thermophilic organism
      Thermus Rt41A.
AB  - A proteinase isolated from Thermus RT41a was immobilized to controlled pore glass
      beads and was used in the free and immobilized forms for peptide synthesis. The
      observed maximum yield was the same in both cases. a number of dipeptides were
      produced from amino acid esters and amides. The best acyl components, from those
      tested, were found to be Ac-Phe-OEt and Bz-Ala-OMe. Tur-NH(2), Trp-NH(2), Leu
      pNA, and Val-pNA were all reactive nucleophiles.The kinetically controlled
      synthesis of Bz-ala-Tyr-NH(2) was optimized by studying the effect of pH,
      temperature, solvent concentration, ionic strength, and nucleophile and acyl
      donor concentration, ionic strength, and nucleophile and acyl donor concentration
      on the maximum yield. The initial conditions used were 25 mM Bz-ala-OMe, 25 mM
      Tyr-NH(2), 70 degrees C, pH 8.0, and 10% v/v dimethylformamide (DMF). The optimum
      conditions were 90% v/v DMF using 80 mM bz-Ala-OMe and 615 mM Tyr-NH(2) at 40
      degrees C and pH 10. These conditions increased the maximum conversion from 0.75%
      to 26% (of the original ester concentration). In a number of other cosolvents,
      the best peptide yields were observed with acetonitrile and ethyl acetate. In 90%
      acetonitrile similar yields were observed to those in 90% DMF under optimized
      conditions except that the acyl donor and nucleophile concentrations could be
      reduced to 25 mM and 100mM, respectively. The effect of the blocking group on the
      nucleophile was also investigated; -betaNA and -pNA as blocking groups improved
      the yields markedly. The blocking and leaving groups of the acyldonor had no
      effect on the dipeptide yield.

PMID- 18618751
TI  - An on-line sampling system for fermentation monitoring using membrane inlet mass
      spectrometry (MIMS): application to phenoxyacetic acid monitoring in penicillin
      fermentation.
AB  - A sampling system for on-line monitoring of organic compounds of low volatility
      in complex fermentation media uses membrane inlet mass spectrometry (MIMS). A
      Syringe pump draws a continuous flow of microfiltered broth from the reactor and
      circulates it after acidification through a membrane inlet, in which a membrane
      is the only interface between the sample and the high vacuum of a mass
      spectrometer. All operations run automatically, i.e., sampling, acidification
      measurement, and calibration. The on-stream acidification enables MIMS monitoring
      of carboxylic acids, as they must be undissociated in order to pass the
      hydrophobic membrane. The performance of the monitoring system was tested by
      measurements of standard solutions of phenoxyacetic acid (POAA, the sie chain
      precursor of penicillin-V) as well as on POAA during 200 h penicillin-V
      fermentation. During the entire fermentation POAA was monitored n low millimolar
      concentrations with high accuracy and fast response to step changes in POAA
      concentration. Tandem mass spectrometry (MS/MS) allowed direct identification of
      peaks in the mass spectrum of the broth that were not accounted for by POAA.
      These peaks were identified as SO(2) and SCO.

PMID- 18618752
TI  - Flotation of cadmium-loaded biomass.
AB  - Biosorption of heavy metal ions such as Cd(2+) by dead biomass has been
      recognized as a potential alternative to existing removal technologies applied to
      wastewater treatment. Two bacterial strains were studied in the laboratory,
      streptomyces griseus and S. clavuligerus, an industrial by-product. Both washed
      and unwashed samples were examined. Foam flotation proposed in this work as the
      separation state following biosorption. Effective biomass separation was
      conducted in the presence of a frother, ethanol. The pH of the solution was a
      crucial parameter for flotation and also for metal binding. Other basic
      parameters of flotation examined were the initial cadmium concentration in the
      dilute aqueous solution and the quantity of biomass used. A study of zeta
      potential measurements of the actinomycetes was carried out under the conditions
      used in the separation; surface tension was also measured. These provided useful
      information on the process.

PMID- 18618753
TI  - Cell cycle kinetics and monoclonal antibody productivity of hybridoma cells
      during perfusion culture.
AB  - The flow-cytometric (FCM) analysis of bivariate DNA/lgG distributions has been
      conducted to study the cell cycle kinetics and monoclonal antibody (MAb)
      production during perfusion culture of hybridoma cells. Three different perfusion
      rates were employed to demonstrate the dependency of MAb synthesis and secretion
      on cell cycle and growth rate. The results showed that, during the rapid growth
      period of perfusion culture, the level of intracellular igG contents of hybridoma
      cells changed significantly at each perfusion rate, while the DNA histograms
      showing cell cycle phases were almost constant. Meanwhile, during the reduced
      growth period of perfusion culture, the fraction of cells in the S phase
      decreased, and the fraction cells in the G1/G0 phase increased with decreasing
      growth rate. The fraction of cells in the G2/M phase was relatively constant
      during the whole period of perfusion culture. Positive correlation was found
      between mean intracellular IgG contents and the specific MAb production rate,
      suggesting that the deletion of intracellular IgG contents by a flow cytometer
      could be used as a good indicator for the prediction of changes in specific MAb
      productivity following manipulation of the culture condition.

PMID- 18618754
TI  - Morphological kinetics and distribution in somatic embryo cultures.
AB  - The environmental effects on developing somatic embryos should be characterized
      not only by the growth based on biomass, but also by the morphological properties
      and size. We have previously developed a discrete classifier to separate
      developing embryos into distinct morphological classes. In this study, a
      continuous descriptor using the distributions of magnitude of features
      representing morphological characteristics and size information was used to
      describe the developing embryo populations. The identity of the population was
      examined by comparing either the distributions of all features or key features.
      The method was applied to characterize the kinetics of carrot embryo populations
      cultivated in the presence and absence of triiodobenzoic acid(TIBA), an inhibitor
      of auxin polar transport. Optimal sample size for morphological characterization
      was determined by the invariance of feature distributions with further increase
      in sample size. The overall growth and substrate consumption kinetics were only
      slightly affected by the presence of TIBA. However, the distribution of
      morphological features was significantly affected. The features showing the
      highest statistical significance were related to those corresponding to the
      roughness. The continuous descriptor for characterizing developing embryo
      population is potentially useful for quality control in large-scale operations.

PMID- 18618755
TI  - Improvement of the extraction of penicillin acylase from Escherichia coli cells
      by a combined use of chemical methods.
AB  - Several techniques for protein extraction were tested for recovering penicillin
      acylase from a recombinant strain of Escherichia coli. These techniques include
      chemical [guanidine hydrochloride, Triton X-100, ethylenediaminetetraacetic acid
      (EDTA), ethanol/toluene], physical (sonication, freeze-and-thawing), and
      enzymatic (lysozyme) treatments. Best results were obtained with the combined use
      of guanidine and EDTA. This extraction procedure was optimized, and it was found
      that 95% of the enzyme was extracted after a 10 m/M EDTA plus 10 mM guanidine
      treatment at room temperature for 10 h. The purification factor was 25 when
      compared to disruption by sonication. This extraction method could avoid
      purification steps for particular applications.

PMID- 18618756
TI  - Modification of islet of langerhans surfaces with immunoprotective poly(ethylene
      glycol) coatings via interfacial photopolymerization.
AB  - Poly(ethylene glycol) (PEG) has been used previously to alter immune interactions
      and systemic clearance of therapeutic proteins. We present herein chemical
      approaches for the conceptually similar treatment of therapeutic cells and
      tissues whereby immune and cell adhesive interactions may be reduced or
      interrupted, in the context of the transplantation of xenogeneic islets of
      Langerhans for the treatment of insulin-dependent diabetes mellitus. Visible
      light-initiated interfacial photopolymerization of multifunctional PEG-based
      macromers was performed directly upon the surface of rat islets of Langerhans to
      produce conformal barrier hydrogel coatings with thickness of order 10 microm.
      The islets continued to be normal in ultrastructure and function as reflected by
      response to a glucose challenge in vitro.

PMID- 18618757
TI  - Mass transfer limitation of sulfate in methanogenic aggregates.
AB  - The role of mass transfer limitation of sulfate as a factor governing the
      competition between sulfate reducing and methane producing bacteria in
      methanogenic aggregates was theoretically evaluated by the calculation of steady
      state sulfate microprofiles using a reference set of parameters obtained from the
      literature. The shooting method was used as a numerical technique for solving the
      mathematical model. The effect of the parameters on mass transport limitation was
      tested by varying each reference value of the parameters with a factor of 3.
      Sulfate limitation within granules prevailed at moderate (0.1 kg m(-3)) and low
      sulfate concentrations in the bulk liquid, at high maximum sulfate utilization
      rates (3.73 x 10(-5) kg SO(4) (2-) kg(-1) VSS S(-1) or biomass concentrations (40
      KG VSS m(-3)), and in large aggregates (radius of 7.5 10(-4) m). The effective
      diffusion coefficient of sulfate and the affinity constant were less
      determinative for the penetration depth of sulfate within a granule.

PMID- 18618760
TI  - Bayesian variable and model selection methods for genetic association studies.
AB  - Variable selection is growing in importance with the advent of high throughput
      genotyping methods requiring analysis of hundreds to thousands of single
      nucleotide polymorphisms (SNPs) and the increased interest in using these genetic
      studies to better understand common, complex diseases. Up to now, the standard
      approach has been to analyze the genotypes for each SNP individually to look for
      an association with a disease. Alternatively, combinations of SNPs or haplotypes
      are analyzed for association. Another added complication in studying complex
      diseases or phenotypes is that genetic risk for the disease is often due to
      multiple SNPs in various locations on the chromosome with small individual
      effects that may have a collectively large effect on the phenotype. Hence, multi
      locus SNP models, as opposed to single SNP models, may better capture the true
      underlying genotypic-phenotypic relationship. Thus, innovative methods for
      determining which SNPs to include in the model are needed. The goal of this
      article is to describe several methods currently available for variable and model
      selection using Bayesian approaches and to illustrate their application for
      genetic association studies using both real and simulated candidate gene data for
      a complex disease. In particular, Bayesian model averaging (BMA), stochastic
      search variable selection (SSVS), and Bayesian variable selection (BVS) using a
      reversible jump Markov chain Monte Carlo (MCMC) for candidate gene association
      studies are illustrated using a study of age-related macular degeneration (AMD)
      and simulated data.

PMID- 18618761
TI  - Impaired performance of FDR-based strategies in whole-genome association studies
      when SNPs are excluded prior to the analysis.
AB  - With recent advances in genomewide microarray technologies, whole-genome
      association (WGA) studies have aimed at identifying susceptibility genes for
      complex human diseases using hundreds of thousands of single nucleotide
      polymorphisms (SNPs) genotyped at the same time. In this context and to take into
      account multiple testing, false discovery rate (FDR)-based strategies are now
      used frequently. However, a critical aspect of these strAtegies is that they are
      applied to a collection or a family of hypotheses and, thus, critically depend on
      these precise hypotheses. We investigated how modifying the family of hypotheses
      to be tested affected the performance of FDR-based procedures in WGA studies. We
      showed that FDR-based procedures performed more poorly when excluding SNPs with
      high prior probability of being associated. Results of simulation studies
      mimicking WGA studies according to three scenarios are reported, and show the
      extent to which SNPs elimination (family contraction) prior to the analysis
      impairs the performance of FDR-based procedures. To illustrate this situation, we
      used the data from a recent WGA study on type-1 diabetes (Clayton et al. [2005]
      Nat. Genet. 37:1243-1246) and report the results obtained when excluding or not
      SNPs located inside the human leukocyte antigen region. Based on our findings,
      excluding markers with high prior probability of being associated cannot be
      recommended for the analysis of WGA data with FDR-based strategies.

PMID- 18618762
TI  - Effects of RH-5992 on ecdysteroidogenesis of the prothoracic glands during the
      fourth larval instar of the silkworm, Bombyx mori.
AB  - Stage-dependent effects of RH-5992 on ecdysteroidogenesis of the prothoracic
      glands during the fourth larval instar of the silkworm, Bombyx mori, were studied
      in the present report. When larvae were treated with RH-5992 during the early
      stages of the fourth larval instar (between day 0 and day 1), initially
      ecdysteroid levels in the hemolymph were inhibited. However, 24 h after RH-5992
      application, ecdysteroid levels were greatly increased as compared with those
      treated with acetone. The examination of the in vitro prothoracic gland activity
      upon RH-5992 application during the early stages of the fourth larval instar
      confirmed a short-term inhibitory effect. When RH-5992 was applied to the later
      stages of the fourth larval instar, no effects on both hemolymph ecdysteroid
      levels and prothoracic gland activity were observed. Addition of RH-5992 to
      incubation medium strongly inhibited ecdysteroid secretion by the prothoracic
      glands from the early fourth instar, indicating direct action of RH-5992 on
      ecdysteroidogenesis by prothoracic glands. Four hours after application with RH
      5992 on day 1.5, prothoracic glands still showed an activated response to PTTH in
      both PTTH-cAMP signaling and the extracellular signal-regulated kinase (ERK)
      signaling. Moreover, addition of RH-5992 to incubation medium did not interfere
      with the stimulatory effect of the glands to PTTH in ecdysteroidogenesis. These
      results indicated that both PTTH-cAMP signaling and PTTH-ERK signaling may not be
      involved in short-term inhibitory regulation by RH-5992.

PMID- 18618763
TI  - Juvenile hormone induction of glutathione S-transferase activity in the larval
      fat body of the common cutworm, Spodoptera litura (Lepidoptera: Noctuidae).
AB  - The effect of pyriproxyfen, a juvenile hormone analog (JHA), on the pupation of
      S. litura was examined. A topical application of 100 mug JHA/larva on the newly
      ecdysed (0-day) sixth instar larvae resulted in more than 80% pupation, while
      most of the 1- or 2-day-old larvae similarly treated developed into supernumerary
      larvae. Glutathione S-transferse (GST) activity in the fat body of 0-day-old
      sixth instar larvae was significantly induced within 12 h of JHA (100
      microg/larva) treatment. In contrast, no such induction was found when 1- and 2
      day-old sixth instar larvae were similarly treated. This induction phenomenon was
      also observed when 0-day-old sixth instar larvae were treated with the natural JH
      III. The suppressive effects of alpha-amanitin and cycloheximide suggest that JHA
      induction of GST activity in these cutworm larvae presumably occurred at the gene
      transcription level.

PMID- 18618764
TI  - Biogenic amine levels change in the brains of stressed honeybees.
AB  - Three different stress treatments, CO2 anesthesia, chilling anesthesia, and
      vertical spin, were applied to test whether honeybee (Apis mellifera) workers
      express stress responses in rewarding behaviors. In the present work, we defined
      the rewarding behaviors as the bees flying between the hive and feeder. The
      results from behavioral observation show that the flight time interval of the
      rewarding behavior of bee workers, flying between hive and feeder, was longer
      when they were stressed, suggesting that the stress treatments affected the
      workers' rewarding behavior. The biogenic amine levels in the workers' brains
      were measured to examine the rapid biochemical brain response to the stressors.
      After the chilling anesthesia, the dopamine (DA) and octopamine (OA) levels were
      significantly decreased; with the CO2 anesthesia for durations of both 2 min and
      4 min, only DA showed a significant decrease. In the non-anesthesia treatments,
      the vertical spin with a velocity of 50 and 60 rpm for 90 s, the DA and OA levels
      were significantly decreased. Our results suggest that when the bees were under
      stress, the brain levels of OA and DA were depressed, and this may have caused
      latency in the rewarding behavior. The serotonin (5-HT) levels under these stress
      treatments were not changed.

PMID- 18618765
TI  - Preface: Insect science in Taiwan.

PMID- 18618766
TI  - Mapping the cellular network of the circadian clock in two cockroach species.
AB  - The German cockroach, Blattella germanica, and the double-striped cockroach, B.
      bisignata, are sibling species with a similar period sequence but a distinctive
      circadian rhythm in locomotion. The cell distribution of immunoreactivity (ir)
      against three clock-related proteins, Period (PER), Pigment Dispersing Factor
      (PDF), and Corazonin (CRZ), was compared between the species. The PER-ir cells
      tend to form clusters and are sprayed out in the central nervous system. Three
      major PER-ir cells are located in the optic lobes, which are the sites of the
      major circadian clock. They are interconnected with PER-ir axon bundles.
      Interestingly, the potential output signal of the circadian clock, PDF, is co
      localized with PER in all three groups of cells. However, only two CRZ-ir cells
      and their axons are found in the optic lobes and they are not co-localized with
      PER-ir or PDF-ir cells and axons. Since only one circadian rhythm is expressed in
      locomotion, the time signals from both major clocks in optic lobes are coupled by
      connection with PDF-ir axons. A group of 3-4 PER-ir cells in the protocerebrum
      display typical characteristics of neurosecretary cells. In addition, there are
      numerous, small PER-ir and PDF-ir co-localized cells in the pars intercerebralis
      (PI), which have direct connections with the neurohemoorgan, corpora cardiaca,
      through PER-ir and PDF-ir axons. Based on these findings, the cellular connection
      shows a circadian control through the endocrine route. For the rest of central
      nervous system, only a few PER-ir and PDF-ir cells or axons are detected. This
      finding implies the circadian clock for locomotion is not located in
      subesophageal ganglion, thoracic or abdominal ganglia, but may use other neural
      messengers to pass on circadian signals. Since the overall distribution pattern
      of the clock cells are the same for B. germanica and B. bisignata, the possible
      explanation for the different expressions of locomotion between the species
      depends on genes downstream of per, pdf, and crz.

PMID- 18618767
TI  - Abnormal mitosis in hypertetraploid cells causes aberrant nuclear morphology in
      association with H2O2-induced premature senescence.
AB  - Aberrant nuclear morphology, such as nuclei with irregular shapes or fragmented
      nuclei, is often observed in senescent cells, but its biological significance is
      not fully understood. My previous study showed that aberrant nuclear morphology
      in senescent human fibroblasts is attributable to abnormal mitosis in later
      passages. In this study, the production of abnormal nuclei in association with
      premature senescence was investigated. Premature senescence was induced by brief
      exposure of human fibroblasts to hydrogen peroxide (H(2)O(2)), and mitosis was
      observed by time-lapse microscopy. In addition, cell cycle and nuclear morphology
      after exposure to H(2)O(2) were also analyzed using a laser scanning cytometer.
      Time-lapse analysis revealed that the induction of premature senescence caused
      abnormal mitoses, such as mitotic slippage or incomplete mitosis, especially in
      later days after H(2)O(2) exposure and often resulted in abnormal nuclear
      morphology. Analysis by laser scanning cytometer showed significantly higher
      frequency of abnormal cells with deformed nuclei and abnormal mitotic cells with
      misaligned chromosomes in a hypertetraploid subpopulation. These results suggest
      that unstable hypertetraploid cells, formed in association with H(2)O(2)-induced
      premature senescence, cause abnormal mitosis that leads to aberrant nuclear
      morphology.

PMID- 18618769
TI  - A nonparametric method for penetrance function estimation.
AB  - In diseases caused by a deleterious gene mutation, knowledge of age-specific
      cumulative risks is necessary for medical management of mutation carriers. When
      pedigrees are ascertained through at least one affected individual, ascertainment
      bias can be corrected by using a parametric method such as the Proband's
      phenotype Exclusion Likelihood, or PEL, that uses a survival analysis approach
      based on the Weibull model. This paper proposes a nonparametric method for
      penetrance function estimation that corrects for ascertainment on at least one
      affected: the Index Discarding EuclideAn Likelihood or IDEAL. IDEAL is compared
      with PEL, using family samples simulated from a Weibull distribution and under
      alternative models. We show that, under Weibull assumption and asymptotic
      conditions, IDEAL and PEL both provide unbiased risk estimates. However, when the
      true risk function deviates from a Weibull distribution, we show that the PEL
      might provide biased estimates while IDEAL remains unbiased.

PMID- 18618770
TI  - Characterization of midgut trypsinogen-like cDNA and enzymatic activity in
      Plutella xylostella parasitized by Cotesia vestalis or Diadegma semiclausum.
AB  - Protein digestion in insects is a result of the action of a complex of
      proteinases present in the midgut. In this report we describe the cloning and
      sequencing of a trypsin cDNA from larvae of the lepidopteran herbivore Plutella
      xylostella. We investigated the expression of this gene and enzymatic activity of
      its translation product with N-a-benzoyl-l-arginine p-nitroanilide (BApNA) as
      substrate in P. xylostella larvae that were either unparasitized or parasitized
      by Cotesia vestalis or Diadegma semiclausum parasitoids. The full cDNA sequence
      consisted of an open reading frame (ORF) encoding 273 amino acid residues
      including 23 residues of a signal peptide, and the predicted mature trypsinogen
      like enzyme had a molecular mass of 26.5 kDa. The amino acid sequence of this
      trypsinogen-like enzyme protein and phylogenetic relationship with other
      published trypsin enzyme proteins suggested that it may be a new proteinase in
      the trypsin protein family. Parasitism of D. semiclausum did not significantly
      change the mRNA transcript level or BApNAase activity in host larvae. By
      contrast, parasitization by C. vestalis induced higher transcript levels coupled
      with a higher level of BApNAase activity. The BApNAase activity in the midgut of
      nonparasitized or parasitized P. xylostella larvae increased to a maximum level
      at pH 12, and the parasitism by both C. vestalis and D. semiclausum increased
      sensitivity of the enzyme to pH values ranging from 2 to 9.5. These parasitoid
      induced changes may represent host manipulation by the developing parasitoid
      larva.

PMID- 18618771
TI  - Predicting phenotypic effects of gene perturbations in C. elegans using an
      integrated network model.
AB  - Predicting the phenotype of an organism from its genotype is a central question
      in genetics. Most importantly, we would like to find out if the perturbation of a
      single gene may be the cause of a disease. However, our current ability to
      predict the phenotypic effects of perturbations of individual genes is limited.
      Network models of genes are one tool for tackling this problem. In a recent
      study, (Lee et al.) it has been shown that network models covering the majority
      of genes of an organism can be used for accurately predicting phenotypic effects
      of gene perturbations in multicellular organisms. .

PMID- 18618773
TI  - Artificial neural network based experimental design procedure for enhancing
      fermentation development.
AB  - Conventional experimental design techniques are available to assist in the
      optimization of fermentation processes, but due to the nonlinearities in the
      bioprocess, they are limited in their effectiveness. This problem is further
      complicated with recombinant systems as a result of the additional complexities
      of the process. This article describes a general strategy using artificial neural
      networks as an alternative approach to fermentation process development
      laboratory are presented for the neural network based procedures. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618774
TI  - Novel redox surfactants and their interactions with glucose oxidase of
      Aspergillus niger.
AB  - A number of novel redox surfactants (based on mixed bipyridine/dipyridylamine
      complexes of osmium (II) where the dipyridylamine ligands bears a saturated C(8),
      C(10), C(12), C(14), or C(16) alkyl chain) were synthesized and characterized
      electrochemically and biochemically as mediators for glucose oxidase (EC 1.1.3.4,
      GOD) of Aspergillus niger. These compounds exhibited critical micelle
      concentrations (CMCs) in phosphate-buffered saline solution (pH 7.4) in the range
      10(-4) 10 10(-3) M, the value decreasing with increasing chain length. Dependence
      of a number of properties (speed of mediation, redox potential, denaturing action
      on the enzyme, adsorption on an electrode surface) on the length of the mediator
      alkyl chain was observed. The presence of an alkyl chain decreased the rate of
      mediation relative to otherwise similar nonsurfactant mediators, and the longer
      alkyl chain, the slower the rate of mediation. For each compound, mediation above
      the CMC was about tenfold slower than that observed below the CMC. However, for
      the cases of mediator absorbed on an electrode surface with GOD, longer chains
      give increased physisorption of mixed micelles of enzyme and mediator. The
      compounds were incidentally found to inhibit the glucose oxidase activity of GOD
      in a complex manner; inhibition increased with increasing chain length and the
      deactivation, for any given compound, was more pronounced below the CMC than
      above. Glucose oxidase activity assays and study of the action of surfactants and
      mediators on the fluorescent properties of carboxy-fluorescein-labeled GOD led to
      the consideration of a model for redox surfactant-GOD interaction where three
      mechanisms may operate: first, a selective interaction of mediators with the GOD
      active site; second, a nondenaturing association of short-chain (<C(14)) cationic
      surfactants; and third, a denaturing action of long-chain ( greater,
      similarC(14)) cationic surfactants. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618775
TI  - A new method for studying microaerobic fermentations. I. A theoretical analysis
      of oxygen programmed fermentation.
AB  - An experimental method for studying microaerobic fermentation, called oxygen
      programmed fermentation, is introduced. The method if based on a chemostat. The
      mathematical equations governing the dynamics of the system are derived and
      simulations are made for two principally different cases: a purely respirative
      organism, and an organism capable of fermentation during oxygen limitation. It is
      shown that at a suitably chosen ramp rate, the dissolved oxygen concentration in
      the broth can be made to decrease almost linearly. It is suggested that the
      greatest use of oxygen programmed fermentation will be in initial experiments.
      Compared with chemostat studies, a scan of different oxygenation rates will
      provide a time-saving method of finding the interacting regions for metabolic
      transitions. Furthermore it is shown that the methods makes it possible to study
      cell physiology at condition which would normally lead to washout. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618776
TI  - A new method for studying microaerobic fermentations. II. An experimental
      investigation of xylose fermentation.
AB  - A new experimental technique, called oxygen programmed fermentation (OPF), was
      used to study microbial cultures of the years Pichia stipitis and Candida utilis
      growing on xylose as carbon and energy source. In the oxygen programmed
      fermentation, the inlet oxygen mole fraction was continuously changed to scan
      through a wide range of oxygen uptake rates in a continuous culture. The largest
      ethanol yields and productivities of P. stipitis were found at oxygen transfer
      rates below 1.5 mmol L(-1) h(-1). It was found that the ratio between the culture
      fluorescence and near-IR absorbance increased at oxygen transfer rates lower than
      1.5 mmol L(-1) h(-1). Small amounts of ethanol were produced also by C. utilis
      when the oxygen transfer rate was between 0 and 3 mmol L(-1) h(-1). It is
      suggested that OPF will form a nice complement to ordinary, microaerobic
      chemostat experiments, by making the identification of interesting regions of
      oxygen transfer rates possible in an efficient and time-saving initial
      experiment. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618777
TI  - Hydrolysis of triglyceride by the whole cell of Pseudomonas putida 3SK in two
      phase batch and continuous reactors systems.
AB  - Batch and continuous hydrolysis of olive oil in an organic-aqueous two-phase
      system using the live whole cell of Pseudomonas putida 3SK as a source of a
      lipase is investigated. The strain was not only fully viable and grown well, but
      also produced extracellular lipase simultaneously. The degree of hydrolysis,
      depending on olive oil concentration in the solvents, was maximal at 13.5% (w/v)
      and decreased with the increase of the substrate concentration. At the optimal
      condition, a degree of hydrolysis higher than 95% was achieved with 24 h at 30
      degrees C when the reaction was carried out in a two-phase batch stirred reactor.
      For long-term operation a continuous stirred reactor was designed. When the
      reaction was carried out in a continuous stirred reactor, the degree was
      hydrolysis reached 86% at a dilution rate of 0.2 h(-1). Satisfactory performance
      of a two-phase bioreactor was obtained in a long-term continous operation, which
      lasted for at least 30 days by feeding organic solvent containing olive oil and
      aqueous media separately. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618778
TI  - Partitioning of pristinamycins in aqueous two-phase systems: A first step toward
      the development of antibiotic production by extractive fermentation.
AB  - The partitioning of pristinamycins was studied in dextran and polyethylene glycol
      (PEG) aqueous two-phases systems. Pristinamycins partitioned preferentially into
      the PEG-rich top phase. The partition coefficient was independent of molar mass
      of PEG and dextran and of antibiotic concentration, but, increased exponentially
      with the tieline length of the system. Partition of pristinamycins was greatly
      improved when fatty acids esters of PEG were mixed with PEG. In such mixtures,
      the partition of coefficient increased up to a value of 24, dependent on the
      carbon chain length of fatty acids and the modified PEG concentrations. Moreover,
      in such system, the two groups of pristinamycins, I and II, were extracted in
      accordance with their hydrophobicity. Recovery of pristinanamycins produced by
      Streptomyces pritinaespiralis in a fermentation broth was achieved with a
      dextran/PEG system. Cells were confined into the bottom phase and pristinamycins
      partitioned in the top phase. However, due to binding of the pristinamycins to
      the cells, the partition coefficient was slightly lower than of pure antibiotics
      solutions. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618779
TI  - Metabolic monitoring by using the rate of change of NAD(P)H fluorescene.
AB  - The amino acid fermentation by Corynebacterium glutamicum was monitored with an
      new technique that uses the first derivative of the NAD(P)H fluorescene signal.
      The rate of change of NAD(P)H pools is indicative of intracellular redox balance
      variations that correspond to metabolic changes. The profile of this signal
      showed several characteristics that coincided with major metabolic events during
      fermentation. We show here that the derivative fluorescence signal can accurately
      estimate points of threonine depletion, viable cell count, and the end of amino
      acid formation. Furthermore, on-line optimization strategies can be developed by
      using the derivative fluorescene signal. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618780
TI  - Effects of oxygen and nutrients limitation on ajmalicine production and related
      enzyme activities in high density cultures of Catharanthus roseus.
AB  - Oxygen and nutrient limitation was investigated in order to identify the origin
      of a lower specific ajmalicine production in Catharanthus roseus cultures at high
      cell densities in an induction medium. The effect of oxygen limitation was
      explored by comparing two identically aerated and agitated high cell density
      bioreactor cultures with dissolved oxygen (DO) concentration of 15% and 85% of
      air saturation, with respect to alkaloid formation and related enzymes
      activities. Oxygen had an evident effect on ajmalicine production: in the high DO
      cultures production was more than 5 times higher than in the low DO cultures. The
      difference in ajmalicine production between high and low DO could not be
      explained by the enzyme activity profiles. Moreover, the productivity in the high
      density culture could not restored to the level of a low density culture (at a
      high DO) by increasing the DO alone. The effect of nutrient limitation was
      studied with response surface methodology in shake flask cultures. Nutrient
      limitation could not be demonstrated to be responsible for the productivity loss.
      Alkaloid and enzyme measurements in the shake flask cultures supported previous
      findings that the tryptamine pathway may regulate alkaloid production, provided
      that the terpenoid pathway is sufficiently active. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18618781
TI  - Feasibility of expanded granular sludge bed reactors for the anaerobic treatment
      of low-strength soluble wastewaters.
AB  - The application of the expanded granular sludge bed (EGSB) reactor for the
      anaerobic treatment of low-strength soluble wastewaters using ethanol as a model
      substrate was investigated in laboratory-scale reactors at 30oC. Chemical oxygen
      demand (COD) removal efficiency was above 80% at organic loading rates up to12 g
      COD/L . d with influent concentrations as low as 100 to 200 mg COD/L. These
      results demonstrate the suitability of the EGBS reactor for the anaerobic
      treatment of low-strength wastewaters. The high treatment performance can be
      attributed to the intense mixing regime obtained by high hydraulic and organic
      loads. Good mixing of the bulk liquid phase for the substrate-biomass contact and
      adequate expansion of the substrate-biomass contact and adequate expansion of the
      sludge bed for the degassing were obtained when the liquid upflow velocity
      (V(up)) was greater than 2.5 m/h. Under such conditions, an extremely low
      apparent K(s) value for acetoclastic methanogenesis of 9.8 mg COD/L was observed.
      The presence of dissolved oxygen in the wastewater had no detrimental effect on
      the treatment performance. Sludge piston flotation from pockets of biogas
      accumulating under the sludge bed occurred at V(up) lower than 2.5 m/h due to
      poor bed expansion. This problem is expected only in small diameter laboratory
      scale reactors. A. more important restriction of the EGSB reactor was the sludge
      washout occurring at V(up) higher than 5.5 m/h and which was intensified at
      organic loads higher than 7 g COD/L. d due to buoyancy forces from the gas
      production. To achieve an equilibrium between the mixing intensity and the sludge
      hold-up, the operation should be limited to an organic loading rate of 7 g COD/L
      d. and to a liquid up-flow velocity between 2.5 and 5.5 m/h (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18618782
TI  - Foaming and cell flotation in suspended plant cell cultures and the effect of
      chemical antifoams.
AB  - Foam development and stability in Atropa belladonna suspensions were investigated
      as a function of culture conditions. Foaming was due mainly to properties of the
      cell-free broth and was correlated with protein content; effects due to presence
      of cells increased towards the end of batch culture. Highest foam levels were
      measured 11 days after inoculation. Air flow rate was of major importance in
      determining foam volume; foam volume and stability were also strongly dependent
      on pH. Foam flotation of plant cells was very effective. After 30 min foaming,
      ca. 55% of cells were found in the foam; this increased to ca. 75% after 90 min.
      Polypropylene glycol 1025 and 2025, Pluronic PE 6100, and Antifoam-C emulsion
      were tested as chemical antifoams. Polypropylene glycol 1025 and Antifoam C at
      concentrations up to 600 ppm had no adverse effect on growth in shake flasks;
      Pluronic PE 6100 has an inhibitory effect at all levels tested. Concentrations of
      polypropylene glycol 2025 and Pluronic PE 6100 as low as 20 ppm reduced foam
      volumes by a factor of ca. 10. Addition of antifoam reduced k(L)a values in
      bubble-column and stirred-tank bioreactors. After operation of a stirred reactor
      for 2 days using Antifoam C for foam control, cell production was limited by
      oxygen due to the effect of antifoam on mass transfer. Theoretical analysis
      showed that maximum cell concentrations and biomass levels decline with
      increasing reactors working volume due to greater consumption of antifoam to
      prevent foam overflow. The results indicate that when chemical foam control is
      used in plant cell cultures, head-space volume and tolerable foam levels must be
      considered to optimize biomass production. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618783
TI  - Transport of bacteria in porous media: I. An experimental investigation.
AB  - The convective transport of concentrated suspension of bacteria in porous media
      is of interest for several processes such as microbial enhanced oil recovery and
      in situ bioremediation. The parameters which affect the transport of the
      bacterium Bacillus licheniformis JF-2, a candidate microorganism for microbial
      enhanced oil recovery, were investigated experimentally in sandpacks. Bacteria
      retention and permeability reduction occurred primarily in the first few
      centimeters upon entering the porous medium. In downstream sections of the
      sandpack, the permeability reduction was low, even in cases in which high cell
      concentrations (10(8) cfu/mL) were detected in the effluent. The effect of (i)
      addition of a dispersant, (ii) linear velocity of injection, (iii) cell
      concentration, (iv) salinity (v) temperature, and (vi) the presence of a residual
      oleic phase were determined experimentally. A lower reduction in permeability and
      a higher effluent bacterial concentration were obtained in the presence of
      dispersant, high injection velocities, low salinities, and at a higher
      temperature. Macroscopic measurements at different linear velocities and in the
      presence or absence of dispersants suggest that the formation of reversible
      microaggregates and multiparticle hydrodynamic exclusion may be the primary
      mechanisms for bacterial retention and permeability reduction. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618784
TI  - Transport of bacteria in porous media: II. A model for convective Transport and
      growth.
AB  - A model is presented for the coupled processes of bacterial growth and convective
      transport of bacteria has been modeled using a fractional flow approach. The
      various mechanisms of bacteria retention can be incorporated into the model
      through selection of an appropriate shape of the fractional flow curve.
      Permeability reduction due to pore plugging by bacteria was simulated using the
      effective medium theory. In porous media, the rates of transport and growth of
      bacteria, the generation of metabolic products, and the consumption of nutrients
      are strongly coupled processes. Consequently, the set of governing conservation
      equations form a set of coupled, nonlinear partial differential equations that
      were solved numerically. Reasonably good agreement between the model and
      experimental data has been obtained indicating that the physical processes
      incorporated in the model are adequate. The model has been used to predict the in
      situ transport and growth of bacteria, nutrient consumption, and metabolite
      production. It can be particularly useful in simulating laboratory experiments
      and in scaling microbial-enhanced oil recovery or bioremediation processes to the
      field. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618785
TI  - Affinity precipitation of an antibody by ligand-modified phospholipids.
AB  - A new method for the selective precipitation of proteins is applied to the
      isolation and purification of an antibody. Ligand-modified phospholipids (LMPs)
      are solubilized by the nonionic ethoxylated alcohol detergent, resulting in small
      (50 to 100 A) micellar aggregates of LMPs and surfactant. When introduced into
      protein solutions containing an antibody for which the LMP has specific affinity,
      the ligand binds to the protein. Hydrophobic interactions between phospholipid
      tail groups bound to the protein molecules result in an insoluble precipitate.
      Polyclonal and monoclonal antibiotin antibody (pABA and mABA) are shown to be
      selectively precipitated using ratios of
      dimyristoylphosphatidylethanolamidobiotin (DMPE-B) to ABA ranging from 1:1 to
      19:1. The kinetics and yield of the precipitation achieve a maximum at a ratio of
      DMPE-B to ABA of approximately 7:1. The kinetics and magnitude of the turbidity
      change are modeled using the Mie theory of light scattering coupled with the
      smoluchowski theory of aggregation. The kinetics are shown to be enhanced
      significantly by the addition of salt. In particular, the addition of 0.5 M
      ammonium sulfate salt increases the rate of precipitation by more than an order
      of magnitude. It is demonstrated that pABA can be recovered with total activity
      yields of 60% to 70% from mixtures containing nonspecific lgG antibodies in very
      high purity (>99%). (c) 1994 John Wiley & Sons, Inc.

PMID- 18618786
TI  - Enzymatic hydrolysis of whey proteins: I. Kinetic models.
AB  - We have studied the enzymatic hydrolysis of whey proteins at pH 8 and50 degrees C
      with two proteases of bacterial origin, MKC Protease 660 L, and one of animal
      origin, PEM 2500 S. Our results show that a greater degree of hydrolysis is
      achieved under the same experimental conditions with the bacterial proteases than
      with the animal one. In our interpretation of the results we propose a mechanism
      in which the hydrolytic reaction is a zero-order one for the substrate, and the
      enzyme denaturalizes simultaneously via a second-order kinetic process due to
      free enzyme attacking enzyme bound to the substrate. Our results also indicate
      that there is an irreversible serine-protease inhibitor in whey proteins. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18618787
TI  - Enzymatic hydrolysis of whey proteins. II. Molecular-weight range.
AB  - Using high-pressure liquid chromatography we studied the distribution of
      molecular weights in whey-protein hydrolysates using the following commercially
      obtained proteases: Alcalasa 0.6 L and Protease 660 L, both bacterial in origin,
      and PEM 2500 S, of animal origin. In each of the systems, the range of molecular
      weights in the hydrolysate depended solely on the degree of hydrolysis (DH)
      achieved. For DH >/= 20, between 65% and 95% of the hydrolysate is made up of
      peptides with a molecular weight of less than 1,000 Da. (c) 1994 John Wiley &
      Sons, Inc.

PMID- 18618788
TI  - Interactions between benzene, toluene, and p-xylene (BTX) during their
      biodegradation.
AB  - A microbial consortium and Pseudomonas strain (PPO1) were used in studying
      biodegradation of benzene, toluene, and p-xylene under aeorbic conditions.
      Studies involved removal of each compound individually as well as in mixture with
      the others. Both cultures exhibited a qualitatively similar behavior toward each
      compound. Both the pure culture and the consortium grew on benzene following
      Monod kinetics, on toluene following inhibitory (Andrews) kinetics, whereas
      neither could grow on P-xylene. Benzene and toluene mixtures were removed under
      cross-inhibitory (competitive inhibition) kinetics. In the presence of benzene
      and/or toluene, p-xylene was cometabolically utilized by both cultures, but was
      not completely mineralized. Metabolic intermediates of p-xylene accumulated in
      the medium and were identified. Benzene and toluene were completely mineralized.
      Cometabolic removal of p-xylene reduced the yields on both benzene and toluene.
      Except for cometabolism, kinetic constants were determined from data analysis and
      are compared with values published recently by other researchers. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618789
TI  - Influence of strain and medium composition on filtration of escherichia coli
      suspensions.
AB  - Cross-flow filtration of Escherichia coli strains was examined at the laboratory
      and pilot scales using Romicon 500,000 molecular-weight-cutoff hollow fiber
      membranes. Both the series resistance and macrosolute polarization models were
      employed to compare performances. Total dissolved solids content above 90 g/L and
      viscosity above 1.1 x 10(-3) pac s of cell-free culture media were found to
      decrease average filtration fluxes by over 60% both in the absence and presence
      of cells. Broth filtration with culture media of dissolved solids levels below 80
      g/L were influenced to a greater extent by harvest cell density. The collodial
      nature of the complex nutrient responsible for the total solids increase affected
      prediction of filtration performance. Differences in strain filterability were
      observed with JM109 preferred over DH5 in high solids-containing media and RR1
      preferred over JM109 in low dissolved solids-containing media. Their research
      demonstrates the importance of cell strain and media selection in the performance
      of early downstream processing steps. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618791
TI  - Effects of water activity on reaction rates and equilibrium positions in
      enzymatic esterifications.
AB  - A technique of continuous water activity control was used to examine the effects
      of water activity on enzyme catalysis in organic media. Esterification catalyzed
      by Rhizopus arrhizus lipase was preferably carried out at a water activity of
      0.33, which resulted in both maximal initial reaction rate and a high yield. When
      Pseudomonas lipase was used as catalyst it was beneficial to start the reaction
      at high water activity (giving the optimal reaction rate with this enzyme) and
      then shift to a lower water activity toward the end of the reaction to obtain a
      high yield. The apparent equilibrium constant of the reaction was influenced by
      the water activity of the organic solvent.

PMID- 18618792
TI  - Symmetric enzyme distribution in asymmetric UF polysulfone membranes.
AB  - Invertase as well as as amyloglucosidase were immobilized within asymmetyric
      ultrafiltration membranes that were prepared from polysulfone or homogeneously
      modified polysulfone. The chemical modification was carried out by sulfonation
      and halomethylation. This additional change of the surface properties of the
      capillaries within the membrane offers the possibilities for various types of
      enzyme fixation, namely adsorption, charge interactions, or covalent bonding. By
      variation of the immobilization conditions the distribution of the enzyme could
      be adjusted over the membrane's cross section. At a distinct enzyme concentration
      in the loading solution a homogeneous enzyme distribution within the membrane
      could be verified. This was shown by diffusion experiments. Under ultrafiltration
      conditions using a solution that contains membrane-impermeable macromolecules as
      well as a membrane-permeable solute like saccharose the residence time within the
      membrane was increased due to gel formation atop the membrane yet the kinetic was
      no affected. The nonpermeable soluble starch was not reacted by the
      amyloglucosidase membrane, indicating that the skin layer was free of enzymes.

PMID- 18618793
TI  - Examination of primary metabolic pathways in a murine hybridoma with carbon-13
      nuclear magnetic resonance spectroscopy.
AB  - Primary metabolism of a murine hybridoma was probed with (13)C nuclear magnetic
      resonance (NMR) spectroscopy. Cells cultured in a hollow fiber bioreactor were
      serially infused with [1-(13)C] glucose, [2-(13)C] glucose, and [3-(13)C]
      glutamine. In vivo spectroscopy of the culture was used in conjunction with off
      line spectroscopy of the medium to determine the intracellular concentration of
      several metabolic intermediates and to determine fluxes for primary metabolic
      pathways. Intracellular concentrations of pyruvate and alanine were very high
      relative to levels observed in normal quiescent mammalian cells. Estimates made
      from labeling patterns in lactate indicate that 76% of pyruvate is derived
      directly from glycolysis; some is also derived from the malate shunt, the
      pyruvate/melate shuttle associated with lipid synthesis and the pentose phosphate
      pathway. The rate of formation of pyruvate from the pentose phosphate pathway was
      estimated to be 4% of that from glycolysis; This value is a lower limit and the
      actual value may be higher. Incorporation of pyruvate into the tricarboxylic acid
      (TCA) cycle appears to occur through only pyruvate dehydrogenase; no pyruvate
      carboxylase activity was detected. The malate shunt rate was approximately equal
      to the rate of glutamine uptake. The rate of incorporation of glucosederived
      acetyl-CoA into lipids was 4% of the glucose uptake rate. The TCA cycle rate
      between isocitrate and alpha-ketoglutarate was 110% of the glutamine uptake rate.

PMID- 18618794
TI  - Biological sulphate reduction using gas-lift reactors fed with hydrogen and
      carbon dioxide as energy and carbon source.
AB  - Feasibility and engineering aspects of biological sulphate reduction in gas-lift
      reactors were studied. Hydrogen and carbon dioxide were used as energy and carbon
      source. Attention was paid to biofilm formation, sulphide toxicity, sulphate
      conversion rate optimization, and gas-liquid mass transfer limitations. Sulphate
      reducing bacteria formed stable biofilms on pumice particles. Biofilm formation
      was not observed when basalt particles were used. However, use of basalt
      particles led to the formation of granules of sulphate-reducing biomass. The
      sulphate-reducing bacteria, grown on pumice, easily adapted to free H(2)S
      concentrations up to 450 mg/L. Biofilm growth rate then equilibrated biomass loss
      rate. These high free H(2)S concentrations caused reversible inhibition rather
      than acute toxicity. When free H(2)S concentrations were kept below 450 mg/L, a
      maximum sulphate conversion rate of 30 g SO(4) (2-)/L x d could be achieved after
      only 10 days of operation. Gas-to-liquid hydrogen mass transfer capacity of the
      reactor determined the maximum sulphate conversion rate.

PMID- 18618795
TI  - Formation and growth of heterotrophic aerobic biofilms on small suspended
      particles in airlift reactors.
AB  - In this article, the conditions for aerobic biofilm formation on suspended
      particles, the dynamics of biofilm formation, and the biomass production during
      the start-up of a Biofilm Airlift Suspension reactor (BAS reactor) have been
      studied. The dynamics of biofilm formation during start up in the biofilm airlift
      suspension reactor follows three consecutive stages: bare carrier, microcolonies
      or patchy biofilms on the carrier, and biofilms completely covering the carrier.
      The effect of hydraulic retention time and of substrate loading rate on the
      formation of biofilms were investigated. To obtain in a BAS reactor a high
      biomass concentration and predominantly continuous biofilms, which completely
      surround the carrier, the hydraulic retention time must be shorter than the
      inverse of the maximum growth rate of the suspended bacteria. At longer hydraulic
      retention times, a low amount of attached biomass can be present on the carrier
      material as patchy biofilms. During the start-up at short hydraulic retention
      times the bare carrier concentration decreases, the amount of biomass per biofilm
      particle remains constant, and biomass increase in the reactor is due to
      increasing numbers of biofilm particles. The substrate surface loading rate has
      effect only on the amount of biomass on the biofilm particle. A higher surface
      load leads to a thicker biofilm.A strong nonlinear increase of the concentration
      of attached biomass in time was observed. This can be explained by a decreased
      abrasion of the biofilm particles due to the decreasing concentration of bare
      carriers. The detachment rate per biofilm area during the start-up is independent
      of the substrate loading rate, but depends strongly upon the bare carrier
      concentration.The Pirt-maintenance concept is applicable to BAS reactors. Surplus
      biomass production is diminished at high biomass concentrations. The average
      maximal yield of biomass on substrate during the experiments presented in this
      article was 0.44 +/- 0.08 C-mol/C-mol, the maintenance value 0.019 +/- 0.012 C
      mol/(C-mol h). The lowest actual biomass yield measured in this study was 0.15 C
      mol/C-mol.

PMID- 18618796
TI  - Frequent harvesting from perfused bone marrow cultures results in increased
      overall cell and progenitor expansion.
AB  - The establishment of prolific long-term human bone marrow cultures has led to the
      development of hematopoietic bioreactor systems. A single batch expansion of bone
      marrow mononuclear cell populations leads to a 10- to 30-fold increase in total
      cell number and in the number of colony forming units-granulocyte/macrophage (CFU
      GMs), and a four- to tenfold increase in the number of long-term culture
      initiating cells (LTC-ICs). In principle, unlimited expansion of cells should be
      attainable from a pool of stem cells if all the necessary requirements leading to
      stem cell maintenance and division are met. In this article, we take the first
      step toward the identification of factors that limit single batch expansion of ex
      vivo bone marrow cells in perfusion-based bioreactor systems. One possible
      constraint is the size of the growth surface area required. This constraint can
      be overcome by harvesting half the cell population periodically. We found that
      harvesting cells every 3 to 4 days, beginning on day 11 of culture, led to an
      extended growth period. Overall calculated cell expansion exceeded 100-fold and
      the CFU-GM expansion exceeded 30-fold over a 27-day period. These calculated
      values are based on growth that could be obtained from the harvested cell
      population. Growth of the adherent cell layer was stable, whereas the nonadherent
      cell population diminished with increasing number of passages. These results show
      that the bioreactor protocols published to date are suboptimal for long-term
      cultivation, and that further definition and refinement is likely to lead to even
      greater expansion of hematopoietic cell populations obtained from bone marrow.
      More importantly, these results show that the LTC-IC measured during the single
      pass expansion do have further expansion potential that can be realized by
      frequent harvesting. Finally, the present culture conditions provide a basis for
      an assay system for the identifications provide a basis for an assay system for
      the identification of the factors that determine the long-term maintenance and
      replication of human stem cells ex vivo.

PMID- 18618797
TI  - Real and pseudo oxygen gradients in Ca-alginate beads monitored during
      polarographic Po2-measurements using Pt-needle microelectrodes.
AB  - Polarographic microcoaxial needle electrodes were used to measure internal
      profiles of dissolved oxygen tension (Po(2)) within single Ca-alginate beads of
      different diameter containing entrapped cells of Saccharomyces cerevisiae. For
      the investigations, single beads coming from variable growing conditions and
      distinct cultivation stages were fixed in a special holding device. In dependence
      on microbial growth steep oxygen gradients were observed. The Oxygen penetration
      depth at steady state lay between 50 and 100 microm. After 8 h of cultivation
      time, the anaerobic space within the beads (phi 2 mm; cultivation in a packed bed
      reactor) is beginning at approximately 130 microm, whereas the anaerobic space
      within the beads (phi 2 mm) coming from the shaker flask culture is located
      approximately 440 microm below the bead surface. Surprisingly, steep gradients
      were also observed, when recording profiles from cell-free Ca-alginate beads of
      different diameter and alginate concentrations. The steep oxygen gradients
      apparently had to be interpreted as pseudo-Po(2)-gradients. These results were
      borne by several effects, such as formation of artifacts and diffusion barriers
      in front of the electrode tip or oxygen "availability" at the tip and consumption
      of oxygen by the electrode itself. These phenomena could be documented by
      microscopic observation and photography. Thus, to obtain real Po(2)-profiles it
      is important to be exactly informed about the physical, chemical, and biological
      properties of the material to be investigated. Furthermore, it is necessary to
      apply a special stepwise puncture technique with distinct step-in/step-out
      movements of the electrode: e.g., unidirectional or contradirectional puncture
      techniques.

PMID- 18618798
TI  - On the use of mild hydrophobic interaction chromatography for "method scouting"
      protein purification strategies in aqueous two-phase systems: a study using model
      proteins.
AB  - The behavior of a series of pure proteins partitioned in aqueous two-phase
      systems is compared with their behavior during mild hydrophobic interaction
      chromatography (HIC). A simple theoretical rationale for this comparison is
      presented based upon solvophobic theory. Similarities were found in the behavior
      of the model proteins in the two forms of partition chromatography. This
      indicates that HIC may be employed as a rapid instrumental technique for the
      broad characterization of protein behavior, which may be of benefit in the
      development of liquid-liquid partitioning strategies. However, it has proved
      difficult to completely account for this behavior on the basis of the known
      physical and structural properties of the proteins used. The variety in the
      detailed partitioning behavior of this small sample of protein types suggests
      that partition in aqueous two-phase systems is uniquely sensitive to subtle
      differences in surface properties of complex macromolecules.

PMID- 18618799
TI  - Liquid flow in heterogeneous biofilms.
AB  - Liquid flow was studied in aerobic biofilms, consisting of microbial cell
      clusters (discrete aggregates of densely packed cells) and interstitial voids.
      Fluorescein microinjection was used as a qualitative technique to determine the
      presence of flow in cell clusters and voids. Flow velocity profiles were
      determined by tracking fluorescent latex spheres using confocal microscopy.
      Liquid was flowing through the voids and was stagnant in the cell clusters.
      Consequently, in voids both diffusion and convection may contribute to mass
      transfer, whereas in cell clusters diffusion is the dominant factor. The flow
      velocity in the biofilm depended on the average flow velocity of the bulk liquid.
      The velocity profiles in biofilms were linear and the velocity was zero at the
      substratum surface. The velocity gradients within biofilms were 50% of that near
      walls without biofilm coverage. The influence of the biofilm roughness on the
      flow velocity profiles was similar to that caused by rigid roughness elements.

PMID- 18618800
TI  - Ethene removal from a synthetic waste gas using a dry biobed.
AB  - A packed granular activated carbon (GAC) biobed, inoculated with the ethane
      degrading strain Mycobacterium E3, was used to study ethene removal from a
      synthetic waste gas. Ethene, for which the dimensionless partition coefficient
      for an air-water system at 20 degrees C is about 7.6, was used as a model
      compound for poorly water soluble gaseous pollutants. In a first mode or
      operation, the GAC biobed was sprinkled intermittently and the waste gas influent
      was continuously pre-humidified, establishing relatively moist conditions (water
      content >40% to 45%). A volumetric ethene removal rate of 0.382 kg COD x m(-3) x
      d(-1) (0.112 kg ethene x m(-3) x d(-1)) was obtained for an influent
      concentration of 125 ppm, a superficial waste gas velocity of 3.6E-3 m x s(-1)
      and a pseudo residence time of 45 s. However, in the second mode of operation,
      omitting the pre-humidification of the waste gas influent and establishing a
      "dry" biobed (water content <40% to 45%), and thus obtaining better mass transfer
      to the biofilm, the ethene removal could be doubled for otherwise comparable
      operating parameters. Furthermore, under decreased wetting and for the given
      experimental conditions (influent concentration 125 to 816 ppm, waste gas
      superficial velocity 3.0E-3 m x s(-1), pseudo waste gas residence time 43 s), the
      ethene removal was not limited by mass transfer of ethene through the water layer
      covering the biofilm.

PMID- 18618801
TI  - A quantitative analysis of shear effects on cell suspension and cell culture of
      perilla frutescens in bioreactors.
AB  - The short-time effects of shear on suspended cells of Perilla frutescens were
      quantitatively analyzed by exposing the cells to a well-defined flow field in a
      rotating drum reactor. It was found that both shear rate and shearing time
      significantly affected cell viability. The quantitative effects of shear on cell
      growth and the production of anthocyanin, a secondary metabolite, by the cell
      cultures were further investigated in a series of batch cultivations using a 5-L
      plant cell bioreactor with a marine impeller. The results indicated that there
      was an optimum range of shear rate; i.e., an average shear rate of 20 to 30 s(-1)
      or an impeller tip speed of 5 to 8 dm/s, which maximized all the values of the
      following parameters: the specific growth rate, the maximum cell concentration,
      the (specific) production and productivity of anthocyanin, and the cell and
      anthocyanin yields.

PMID- 18618802
TI  - Hyphal vocuolation and fragmentation inpenicillium chrysogenum.
AB  - A link between vacuolation and fragmentation of Penicillium chrysogenum mycelia
      in stirred tank submerged fermentations is reported. Quantitative information on
      vocuolation and morphology was obtained by image analysis. In fed-batch
      fermentations the coincidence of the events of rapid vacuolation and the fall of
      the mean total and main hyphal lengths suggests that hyphal fragmentation is not
      necessarily due to "shear" alone. The physiological state of the hyphae,
      characterized by the proportions of vaccuoles, was found to have a significant
      influence on the breakage of mycelial hyphae, It was found that the fragmentation
      was greater when the hyphae became heavily vacuolated following nutrient
      limitation in the culture, i.e., during the switch from the rapid growth to the
      production phase.

PMID- 18618803
TI  - A practical approach to biosurfactant production using nonaseptic fermentation of
      mixed cultures.
AB  - Non-aseptic production of biosurfactant from molasses by a mixed culture was
      investigated in stirred batch reactors. Biosurfactant production was quantified
      by surface tension reduction, critical micelle dilution (CMD), and emulsification
      capacity (EC). Biosurfactant production was directly correlated with biomass
      production, and was improved by pH control and addition of yeast extract.
      Centrifugation of the whole broth increased emulsifying capacity and reduced
      surface tension. Acidification of the whole broth increased the emulsification
      capacity but reduced the apparent biosurfactant concentration (CMD), without
      affecting the surface tension. The emulsification capacity of the cell-free broth
      was equivalent to that of a 100 mg/L solution of sodium dodecyl sulfate. The
      emulsification capacity of the whole broth and cell-free broth were reduced by
      about 50% at and above NaCl concentrations of 100mM. Preliminary characterization
      suggests that the biosurfactant activity is primarily associated with one or more
      protease-sensitive species, released from cells in larger quantities after more
      vigorous centrifugation.

PMID- 18618804
TI  - Sampling flower scent for chromatographic analysis.
AB  - The analysis of flower volatiles requires special methods for their isolation
      with enrichment. Living flowers show a continuous change in their volatile
      profile that depends on intrinsic (genetic) and external (light, temperature,
      hydric stress) factors. Excised flowers suffer rapid deterioration and loss of
      volatiles. While industrial isolation methods for flower volatiles are well
      established, those at the laboratory-scale experience progressive development, in
      the search for higher sensitivity, reproducibility, and simplicity. This review
      covers the flower scent sampling methods most commonly employed during the last
      decade, and includes comments on their strengths and limitations. The strengths
      of headspace solid-phase microextraction (HS-SPME) for in vivo monitoring are
      emphasized with the examples of monitoring the circadian variation of Brugmansia
      suaveolens flower scent and of volatile aldehyde detection in flower scent using
      on-fiber derivatization.

PMID- 18618805
TI  - Woody pretzels: spirocycles from vetiver to patchouli and Georgywood.
AB  - This review, including new experimental results, is the summary of a talk at the
      RSC/SCI conference 'flavours & fragrances 2007' in London, Imperial College, 24
      26 September, 2007. Though the third dimension of the receptor models of J. E.
      Amoore rarely was exceeding 4 A, the world of woody odorants such as (+)-cedrol
      (3; cedarwood), (-)-khusimone (4; vetiver), and (-)-patchoulol (5; patchouli) is
      anything but flat. Any tricyclic skeleton with a zero-bridge contains a
      spirocyclic ring system determining its 3D structure, so spirocycles (spira, Lat.
      pretzel) are the fastest access to the third dimension. In the vetiver family, a
      spirocyclic mimic 9 of (-)-khusimone (4) was first discovered by chance by Buchi
      in 1976, and also by chance, we obtained another system, 12, with a
      characteristic vetiver smell by tandem-Rupe-Nazarov reaction of alkyne diols. A 5
      A distance between a quaternary C-atom and a carbonyl group (or alternative HB
      acceptor) with an alpha-methyl or methylene branching is proposed to be the key
      to their vetiver odor. Upon scale-up of one of these odorants, 24, we discovered
      a very powerful (0.067 ng/l) impurity with a most typical patchouli scent: the
      spirocyclic, sterically crowded hydroxy ketone 33--a most unusual structure for a
      patchouli odorant. Several spirocyclic hydroxy ketone analogs, also with inverted
      ring systems such as in 70 and 84, provided new insights into the structure-odor
      correlation of this family. A superposition analysis indicated the carbonyl
      function of the hydroxy ketone to overlay on the geminal dimethyl motive of (-)
      patchoulol. And indeed, the corresponding hydroxy ketone of patchoulol, 59,
      synthesized in 13 steps from Cyclal C (63), also emanated a patchouli odor.
      Finally, the synthesis and olfactory properties of twelve rigid spirocyclic
      analogs, 95-97, 99-102, and 106-110, of Georgywood (91) are presented that
      highlight stereochemical requirements for woody odorants and raise doubts about
      an alpha-helical binding motive postulated by Hong and Corey.

PMID- 18618806
TI  - Perfume formulation: words and chats.
AB  - What does it mean to create fragrances with materials from chemistry and/or from
      nature? How are they used to display their characteristic differences, their own
      personality? Is it easier to create with synthetic raw materials or with
      essential oils? This review explains why a perfume formulation corresponds in
      fact to a conversation, an interplay between synthetic and natural perfumery
      materials. A synthetic raw material carries a single information, and usually is
      very linear. Its smell is uniform, clear, and faithful. Natural raw materials, on
      the contrary, provide a strong, complex and generous image. While a synthetic
      material can be seen as a single word, a natural one such as rose oil could be
      compared to chatting: cold, warm, sticky, heavy, transparent, pepper, green,
      metallic, smooth, watery, fruity... full of information. Yet, if a very small
      amount of the natural material is used, nothing happens, the fragrance will not
      change. However, if a large amount is used, the rose oil will swallow up
      everything else. The fragrance will smell of nothing else except rose! To
      formulate a perfume is not to create a culinary recipe, with only dosing the
      ingredients in well-balanced amounts. To formulate rather means to flexibly knit
      materials together with a lively stitch, meeting or repelling each other,
      building a pleasant form, which is neither fixed, nor solid, nor rigid. A
      fragrance has an overall structure, which ranges from a clear sound, made up of
      stable, unique, and linear items, to a background chat, comfortable and
      reassuring. But that does, of course, not mean that there is only one way of
      creating a fragrance!

PMID- 18618807
TI  - New developments in umami (enhancing) molecules.
AB  - As health has become one of the main drivers in nutrition, the scientific
      interest in taste receptors and taste molecules has increased considerably.
      Academia as well as flavor and food companies are searching for molecules that
      make food more healthy but not less appetizing. In the savory area, salt and
      umami taste are being investigated. This review deals with the progress made in
      umami tasting molecules. Umami taste has been known as a separate taste for a
      long time in Asian countries and has been generally accepted as the fifth basic
      taste in the last decade of the previous century. In this review, first the
      current level of understanding of the umami receptors will be described. The main
      part of the paper will deal with the umami-tasting molecules that have been
      published recently, including the work that has been performed within Givaudan
      itself. Lactoyl amides of GMP (guanosine monophosphate) appeared to have
      remarkably strong umami-tasting properties.

PMID- 18618813
TI  - [Excessive body fat increases the risk of cancer].

PMID- 18618815
TI  - [The development of ergot alkaloids as drugs].

PMID- 18618816
TI  - [The importance of phytotherapy for benign prostatic syndrome].

PMID- 18618818
TI  - [In memoriam--Franz Carmine].

PMID- 18618826
TI  - Kinetics of growth and elemental sulfur oxidation in batch culture of
      thiobacillus ferrooxidans.
AB  - The kinetics of oxidation of elemental sulfur by Thiobacillus ferrooxidans in a
      batch reactor was followed by measuring the concentration of adsorbed cells on
      the sulfur surface, the concentration of free cells in liquid medium, and the
      amount of sulfur oxidized. As the elemental sulfur was oxidized to sulfate, the
      liquid-phase concentration of free cells continued to increase with time, whereas
      the surface concentration of adsorbed cells per unit weight of sulfur approached
      a limiting value, i.e., the maximum adsorption capacity. During sulfur oxidation,
      there was a close correlation between the concentrations of adsorbed and free
      cells, and these data were well correlated with the Langmuir isotherm. The
      observed rates of batch growth and sulfur oxidation were consistent with a
      kinetic model, assuming that the growth rate of batch growth and sulfur oxidation
      were consistent with a kinetic model. Assuming that the growth rate of adsorbed
      bacteria is proportional to the product of the concentration of adsorbed cells
      and the fraction of adsorption sites unoccupied by cells. The kinetic and
      stoichiometric parameters appearing in the model were evaluated using the
      experimental data and were compared with parameters determined previously for a
      few metal sulfides.

PMID- 18618827
TI  - Protein extraction by reverse micelles: studies on the recovery of horseradish
      peroxidase.
AB  - Phase transfer studies were carried out on the solubilization of horseradish
      peroxidase (HRP) (E.C. 1.11.1.7) in reverse micelles formed in isooctane using
      the anionic surfactant, aerosol OT, at concentrations between 50 and 110 mM. The
      selectivity of this methodology was tested, because the HRP used comprised a
      mixture of seven different isoenzymes with a wide range of isoelectric points.
      Forward and backward transfers were carried out in wellstirred vessels until
      equilibrium was reached. Significant protein partitioning could only be obtained
      by using NaCl to adjust ionic strength in pH range between 1.5 and 3.5, with a
      maximum at pH 3. The back transfer process was best at pH 8 with 80 mM phosphate
      buffer and 1 M KCI. A loss of 1% to 3% of the surfactant through precipitation at
      the interface at pH<4 was observed, which may be due to instability in this pH
      region, because, even without protein, a similar precipitate was noticed. Protein
      partitioning was approximately constant when the ionic strength was increased up
      to 1 MNaCl at pH 3, but protein recovery in back transfer decreased accordingly.
      Hydrophobic interactions together with association between the protein and
      surfactant might be responsible for that behavior. Protein partitioning remained
      the same when the surfactant concentration was decreased to 50 mM, at the expense
      of higher variability. HPLC chromatograms showed no apparent damage to the
      protein after reverse micellar extraction. Protein partitioning is best when the
      temperature is kept at 25 degrees C. The amount of protein and specific activity
      recovered strongly depends on the phase ratio used during forward transfer.
      Overall activity recovery varied from 87% to 136% when the phase ratio was
      increased from 1:1 to 30:1 in forward transfer. This behavior may be due to a
      change in the ratio of the three isoenzymes recovered after the backward transfer
      process, with the most active one being increasingly enriched at higher phase
      ratios.

PMID- 18618828
TI  - Solid-state enzyme deactivation in air and in organic solvents.
AB  - Thermal deactivation of solid-state acid phosphates (E.C. 3.1.3.2, from potato)
      is analyzed, both in the presence and in the absence of organic solvents. The
      thermal deactivation profile departs from first order kinetics and shows an
      unusual activity. The process is described by a phenomenological equation, whose
      theoretical implications are also discussed. The total amount of buffer salts in
      the enzyme powder dramatically affects enzyme stability in the range 70 degrees C
      to 105 degrees C. The higher salt/protein ratio increases the rate of thermal
      deactivation. The deactivation rate is virtually unaffected by the presence of
      organic solvents, independent of their hydrophilicity.

PMID- 18618829
TI  - Separation of amino-acid enantiomers using micellar-enhanced ultrafiltration.
AB  - Micellar-enhanced ultrafiltration (MEUF) is investigated as a large-scale
      technique for separating amino acid enantiomers. Specifically, L-5-cholesterol
      glutamate, a chiral ligand-exchange cosurfactant, is used together with a
      nonionic surfactant to form mixed micelles that preferentially bind D
      phenylalanine over L-phenylalanine in the presence of copper(II). Operational
      selectivities as high as 4.2 are obtained. Potentiometric titrations using a
      water-soluble model compound similar to the chiral cosurfactant indicate that the
      ternary copper complex with phenylalanine has a stereoselectivity for the D
      enantiomer which is significantly smaller than that observed in the MEUF system.
      Thus, the selectivity of the chiral legend's local solvent and structural
      environment.

PMID- 18618830
TI  - Behavior of spores of Penicillium roquefortii during fed-batch bioconversion of
      octanoic acid into 2-heptanone.
AB  - The bioconversion of octanoic acid into 2-heptanone by spores of Penicillium
      roquefortii is performed using a fed-batch technique with pH control by addition
      of the liquid substrate itself. The early stage of this process takes place with
      a high bioconversion rate and high yield. These values then decrease as a result
      of germination and growth the biocatalyst. An optimization strategy for the
      process would thus be to improve the characteristics of this first period, i.e.,
      increase its duration and the reaction rate. An increase in duration is evidenced
      in two cases: (I) under oxygen limitation: and (ii) when the spore content in the
      medium is less than 10(7) spores/mL. These conditions give insufficient overall
      bioconversion rates: better optimization should be achieved without oxygen
      limitation and with high spore content. Characterization of the first period by
      material and bioenergetic balances suggests that an increase in the ethanol
      content of the medium, which acts as an energy source and a permeabilizer, and
      the use of specific inhibitor of the Krebs cycle, may be a way to further improve
      the biocatalyst performance and stability.

PMID- 18618831
TI  - Modeling and optimization of the baculovirus expression vector system in batch
      suspension culture.
AB  - A mathematical model has been developed that predicts the cell population
      dynamics and production of recombinant protein and infective extracellular virus
      progeny by insect cells after infection with baculovirus in batch suspension
      culture. Infection in the model is based on the rate of virus attachment to
      suspended insect cells under culture conditions. The model links the events
      following infection with the sequence of gene expression in the baculovirus
      replicative cycle. Substrate depletion is used to account for the decrease in
      product yield observed when infecting at high cell densities. Model parameters
      were determined in shaker flasks for two media: serum-supplemented IPL-41 medium
      and serum free Sf900II medium. There was good agreement between model predictions
      and the results from an independent series of experiments performed to validate
      the mode. The model predicted: (1) the optimal time of infection at high
      multiplicity of infection: (2) the timing and magnitude of recombinant protein
      production in a 2-L bioreactor; and (3) the timing and magnitude of recombinant
      protein production at multiplicities of infection from 0.01 to 100 plaque-forming
      units per cell. Through its ability to predict optimal infection strategies in
      batch suspension culture, the model has use in the design and optimization of
      large-scale systems for the production of recombinant products using the
      baculovirus expression vector system.

PMID- 18618832
TI  - Cell death in bioreactors: a role for apoptosis.
AB  - The incidence of apoptotic and necrotic cell death was compared in CHO, SF9
      insect cells and murine plasmacytoma (J558L) and hybridoma (TB/C3) cells during
      in vitro cultivation in batch cultures. Acridine orange staining and fluorescence
      microscopy enabled the visualization of a classic morphological feature of
      apoptotic cell, the presence of condensed and/or fragmented chromatin. DNA gel
      electrophoresis was employed to show an additional characteristic of the process,
      the endonuclease-mediated fragmentation of DNA into multiples of 180 base pairs.
      The levels of apoptosis at the end of batch cultures of plasmacytoma and
      hybridoma cell lines were found to be 60% and 90% of total dead cells,
      respectively. However, employing the above-mentioned techniques, the biochemical
      and morphological features of apoptosis were not found in CHO and SF9 insect
      cells. Some factors affecting the induction of apoptosis during the batch culture
      of the hybridoma and plasmacytoma cell lines were identified. The most effective
      inducer was found to be glutamine limitation, followed by (in order of
      importance) serum limitation, glucose limitation, and ammonia toxicity. Blockage
      of the cell cycle of the plasmacytoma and hybridoma cells using thymidine
      resulted in the induction of apoptosis. This has important implications for the
      development of cell culture processes that minimize cell division and thereby
      increase specific productivity.

PMID- 18618833
TI  - Characterization of a recombinant antibody produced in the course of a high yield
      fed-batch process.
AB  - Many mammalian cell fed-batch processes rely on maintaining the cells in a viable
      and productive state for extended periods of time in order to reach high final
      concentrations of secreted protein. In the work described herein, a nonamplified
      NSO cell line was transfected with a vector expressing a recombinant human anti
      HIV gp 120 monoclonal antibody (Mab) and a selectable marker, glutamine
      synthetase. A fed-batch process was developed which improved product yields
      tenfold over the yields reached in batch culture. In this case, the clone was
      cultured for a period of 22 days and produced 0.85 g Mab/L. To gauge the effect
      of extended culture lifetime on product quality, biochemical characteristics of
      MAb isolated from different time points in the fed-batch culture were determined.
      The apparent molecular weight of the MAb was constant throughout the course of
      the culture. Isoelectric focusing revealed four major charged species, with a
      fifth more acidic species appearing later in the culture. The antigen binding
      kinetics were constant for MAb isolated throughout the culture period.
      Glycosylation analysis, on the other hand, revealed that MAb produced later in
      the culture contained greater percentages of truncated N-acetylglucosamine and
      highmannose N-glycans. Possible contributions to this underglycosylated material
      from either cell lysis or synthesis from noviable cells were found to be
      negligible. Instead, the viable cells appeared to be secreting more truncated and
      high mannose MAb glycoforms as the culture progressed.

PMID- 18618834
TI  - The release of virus-like particles from recombinant Saccharomyces cerevisiae:
      effect of freezing and thawing on homogenization and bead milling.
AB  - Recombinant cells of Saccharomyces cerevisiae, expressing virus-like particles
      (Ty-VLPs), can be readily disrupted in a high pressure homogenizer and show
      identical disruption kinetics to the untransformed host strain. When the cells
      are freeze/thawed before disruption, they become about four times more resistant
      to homogenization. This effect increases with the number of freeze/thaw cycles,
      but is independent of the time the cells remain frozen. The freeze/thaw effect is
      observed with cells harvested during both the logarithmic and stationary phase of
      growth, and occurs with the untransformed host strain as well as the transformed
      one. Freeze/thawed cells are twice as resistant to disruption in the bead mill as
      fresh cells.

PMID- 18618835
TI  - Ion exchange immobilization of changed beta-galactosidase fusions for lactose
      hydrolysis.
AB  - The use of charged peptides fused to enzymes for immobilization onto ion-exchange
      membranes was explored for the enzyme x-galactosidase. The additional charged
      peptides, containing 1, 5, 11, and 16 aspartates, fused to x-galactosidase, for
      the most part did not interfere with the kinetic behavior for lactose hydrolysis.
      There was a 2-fold decline in V(m) for the 16-aspartate fusion, but the others
      were quite similar to the wild type enzyme (BGWT). BGWT and the fusions all
      retained approximately 50% of their activities when adsorbed onto ion-exchange
      membranes. In contrast to BGWT, the enhanced binding strength of the 11 aspartate
      fusion provided the ability to hydrolyze whey permeate at 0.3 M ionic strength
      without enzyme leakage, and to immobilize the enzyme directly from diluted cell
      extract with 83% purity.

PMID- 18618836
TI  - Modified monoclonal antibody production kinetics kappa/gamma mRNA levels, and
      metabolic activities in a murine hybridoma selected by continuous Culture.
AB  - During long-term continuous culture of the hybridoma cell line 11317, a better
      producing subclone (I1317-SF11), giving improved productivity, has been selected.
      The comparison of the original cell line (I1317-DC) with this subclone revealed
      that although the growth patterns of both clones were similar, both in continuous
      and in batch cultures, considerable differences could be seen between the clones
      with respect to monoclonal antibody (MAB) accumulation, MAB production rate, the
      levels of mRNA coding for heavy and light chains of IgG, and some metabolic
      activities. In continuous culture as well as in batch culture, I1317-SF11 showed
      increased levels of mRNA coding for kappa and gamma chains compared with I1317-DC
      and/or a modified ratio of the mRNA species when compared to that in I1317-DC.
      Using pulse experiments, it could be established that the biosynthesis of both
      chains was augmented in I1317-SF11. Although the kappa and gamma mRNA levels were
      modified or inversed for I1317-SF11, the cells always synthesized more kappa than
      gamma chains. The overall increase in the synthetic activity of I1317-SF11 is
      suggested as one reason for the considerable increase of IgG productivity and
      product accumulation in continuous culture as well as in repeated batch cultures.
      Tests concerning metabolic activity revealed that I1317-SF11 had a predominantly
      glycolytic metabolism independent of growth requirements, whereas for I1317-DC
      the metabolism became increasingly glycolytic with increased growth. The antibody
      yield coefficient of I1317-SF11 on glutamine was significantly higher than that
      of I1317-DC for the continuous culture, whereas the antibody coefficients on
      glucose were almost similar for both clones under the different culture
      conditions used. Both antibody coefficients were considerablly influenced by the
      specific growth rate.All these facts together lead to the conclusion that
      subclone I1317-SF11 uses more of the energy available, or it was the energy
      and/or precursors available for the synthesis and production of MAB more
      efficiently than the thesis and production of MAB more efficiently than the
      original cell line. Although the levels of mRNA coding for heavy and light chains
      of IgG were modified, it could be confirmed that the overall regulation of MAB
      synthesis and -production occurs post-translationally and that at higher growth
      rates, more biosynthetic activity is diverted to biomass production.

PMID- 18618837
TI  - Surfactant-induced breakthrough effects during the operation of two-phase
      biocatalytic membrane reactors.
AB  - Surface-active components, both reactants and products, are frequently
      encountered in two-phase, aqueous-organic, biocatalytic reactions, When such
      reaction are carried out in a membrane reactor, employing a membrane selectively
      wetted by one of the two reactants, changes in the content of these surfactants-
      as a consequence of the progress of the reaction--can lead to wetting transitions
      at the two membrane-liquid interfaces as a result of adsorption of the tenside.
      This can lead to a decrease in the pressure required to cause the, initially,
      nonwetting phase to break through the membrane. Such effects render difficult the
      operation of two-phase membrane bioreactors. Hence, it is necessary to make a
      careful selection of the membrane material and type by considering factors such
      as UF versus MF and low MWCO versus high MWCO to enable the reactor to be
      operated without breakthrough, but without significantly compromising the
      reaction rates that can be maintained.The phenomena leading to breakthrough
      effects are discussed in this paper, and experimental results for the hydrolysis
      of ethyl laurate by lipase from Candida rugosa in a batch flat sheet membrane
      reactor are presented with the reactor operated with a variety of membranes. An
      experimental result showing the decrease in the pressure required to cause
      breakthrough of the organic phase (for the system ethyl laurate-lauric acid
      water) as the content of the highly surface-active lauric acid in the organic
      phase is increased is also presented for an asymmetric, hydrophilic meta-aramid
      ultrafiltration membrane.

PMID- 18618839
TI  - Role of multivesicular bodies and their components in the egress of enveloped RNA
      viruses.
AB  - As an enveloped virus buds, the nascent viral capsid becomes wrapped in a plasma
      membrane-derived lipid envelope, and a membrane fission event is thus necessary
      to separate the virion from the host cell. This membrane fission event is well
      characterised in the case of enveloped RNA viruses, where it is promoted by late
      assembly domains (L-domains) present at the level of specific viral structural
      proteins. Research conducted over the past 10 years has demonstrated that L
      domains represent docking sites for cellular proteins essential for the
      biogenesis of a cellular organelle, the multivesicular body (MVB). In this way,
      enveloped RNA viruses hijack the MVB components to the cellular site where the
      budding is executed. This review will focus on the cellular machinery exploited
      by enveloped RNA viruses in order to be released from infected cells. The role of
      ubiquitin and lipids in viral budding will also be discussed.

PMID- 18618840
TI  - How useful is a screening instrument?

PMID- 18618841
TI  - Morphological aspects of surgical meshes as a risk factor for bacterial
      colonization.
AB  - BACKGROUND: Prosthetic meshes are increasingly popular in abdominal wall
      reconstructive surgery owing to a reduction in hernia recurrence rate. Individual
      meshes have been evaluated with respect to the formation of infectious biofilms,
      but no comprehensive comparison yet exists. The aim of this study was to evaluate
      the effect of the material and morphology of surgical meshes on biofilm growth.
      METHODS: Biofilms of a coagulase-negative staphylococcus, Staphylococcus aureus,
      Escherichia coli and Pseudomonas aeruginosa were grown in vitro on different
      meshes. Intact biofilms were stained fluorescently and evaluated with confocal
      laser scanning microscopy to distinguish dead from live bacteria and slime.
      RESULTS: Numbers of adhering bacteria and the amount of slime in the biofilm were
      dependent on the morphology of the mesh. Hydrophobicity and the presence of
      niches in multifilament meshes contributed most to increased biofilm growth.
      CONCLUSION: The morphological properties of surgical meshes as well as their
      hydrophobicity influence bacterial growth and slime production. Differences in
      slime production may explain why the effectiveness of antibiotic treatment varies
      for different types of mesh.

PMID- 18618842
TI  - The nature of informal caregiving for medically ill older people with and without
      depression.
AB  - OBJECTIVES: To describe patient and caregiver perceptions of the nature of
      informal caregiving in a sample of older medical inpatients with and without
      depression. METHODS: One hundred and fifty-four patient-caregiver pairs were
      recruited from a larger prospective observational study of three groups of
      medical inpatients aged 65 and over, with major, minor, and no depression,
      respectively, and with at most mild cognitive impairment. Interviews were
      conducted at the time of hospital admission to assess characteristics of patients
      (disability, comorbidity, perceptions of support) and caregivers (relationship,
      residence, types of assistance and time spent caregiving). Time spent on the
      physical tasks of caregiving (assistance with activities of daily living,
      physical care, transport) was estimated by all caregivers. Time spent on
      emotional or other support was estimated only for non-coresident caregivers
      RESULTS: In multivariable analyses, neither major nor minor depression was
      associated with time spent on physical support; major depression was associated
      with significantly increased time spent by non-coresident caregivers on emotional
      or other support; minor depression was associated with perceived inadequacy of
      support. CONCLUSIONS: Major depression is independently associated with greater
      time spent by non-coresident caregivers on emotional or other support; minor
      depression is associated with perceived inadequacy of support.

PMID- 18618844
TI  - Improving protein extraction yield in reversed micellar systems through surface
      charge engineering.
AB  - The mechanism of extraction of rat cytochrome b(5) from water into a sodium
      dioctylsulfosuccinate (AOT) micellar organic phase was studied using protein
      engineering of surface charged residues. The extraction behavior of native
      cytochrome b(5) and modified proteins with substitutions of the type glutamic
      acid --> lysine at positions 44 (E44K), 56 (E56K), and 92 (E92K), was studied as
      a function of pH. The results indicate that an important mechanism of extraction
      is an electrostatic interaction of this protein with the negatively charged
      surfactant. We demonstrate that it is possible to improve extraction by
      engineering the protein surface charge, increasing the driving force responsible
      for the protein transfer to the micellar phase. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618845
TI  - Linear constrain relations in biochemical reaction systems III. Sequential
      application of data reconciliation for sensitive detection of systematic errors.
AB  - This article presents a method to test the presence of relatively small
      systematic measurement errors; e.g., those caused by inaccurate calibration or
      sensor drift. To do this, primary measurements-flow rates and concentrations-are
      first translated into observed conversions, which should satisfy several
      constraints, like the laws of conservation of chemical elements. This study
      considers three objectives: 1.Modification of the commonly used balancing
      technique to improve error sensitivity to be able to detect small systematic
      errors. To this end, the balancing technique is applied sequentially in
      time.2.Extension of the method to enable direct diagnosis of errors in the
      primary measurements instead of diagnosing errors in the observed conversions.
      This was achieved by analyzing how individual errors in the primary measurements
      are expressed in the residual vector.3.Derivation of a new systematic method to
      quantitatively determine the sensitivity of the error, is that error size at
      which the expected value of the chisquare test function equals its critical
      value.The method is applied to industrial data demonstrating the effectiveness of
      the approach. It was shown that, for most possible error sources, a systematic
      errors of 2% to 5% could be detected. In given application, the variation of the
      N-content of biomass was appointed to be the cause of errors. (c) 1994 John Wiley
      & Sons, Inc.

PMID- 18618846
TI  - Effects of substrate branching characteristics on kinetics of enzymatic
      depolymerizaion of mixed linear and branched polysaccharides: I.
      Amylose/amylopectin alpha-amylolysis.
AB  - Hydrolysis reactions of homopolysaccharides, which differ in their degree of
      branching, and mixtures of linear and branched polymers were carried out with
      alpha-amylase. The branching structures of both the original amylopectin
      substrate and the cluster domains of amylopectin, obtained by ethanol
      precipitation of the products of the action of alpha-amylase, were characterized
      via enzymatic digestion with debranching enzyme (i.e., isoamylase), followed by
      the fractions of the resulting products using gel filtration chromatography. The
      structural properties (i.e., molecular weight, molecular weight distribution, and
      branching characteristics) of the resulting products during depolymerization of
      amylose, amylopectin and their mixtures via alpha-amylase were characterized by
      size exclusion chromatography coupled with a low angle laser right scattering
      (SEC/LALLS) technique. It was determined that substrate branching characteristics
      strongly influence both the observed enzymatic activity as well as the enzyme's
      action pattern. A simplified kinetic model that represents the hydrolysis
      reactions of amylose and amylopectin mixtures via endo-acting alpha-amylase is
      proposed. We found that that reaction kinetics (i.e., enzyme affinity) was also
      governed by the substrate's conformation in solution. The relationships between
      the mass fraction of branched polymers and the kinetic parameters during alpha
      amylolysis were compared with those predicted by the kinetic model. Excellent
      agreement was found between the model predictions and the experimental
      observations. The results reported here imply and interrelationship between
      enzyme action and polymeric substrate structural properties. (c) 1994 John Wiley
      & Sons, Inc.

PMID- 18618847
TI  - An investigation of the physico-chemical basis of foaming in fungal
      fermentations.
AB  - A detailed physico-chemical analysis of two foaming fungal fermentations was
      carried out to identify that key groups of compounds responsible for foam
      formation. Fermentations were carried out on a 20-L scale in a stirred aerated
      tank, over 7 days, using a commercial, defined medium. The organisms investigated
      were Penicillium herqueii, a hyphomycete, and an unidentified Ingoldian fungus.
      Samples of broth and, where possible, foam were analyzed to determine which
      groups of compounds were concentrated into generated foams. Surface tension, bulk
      viscosity, and antifoam A concentration were additionally determined in broth
      samples. To date the cause of foaming in fermentations has been attributed to the
      surfactant properties of extracellular proteins. This assumption was tested and
      found to be incomplete as many additional groups of biochemicals were found to be
      enriched into the foam. The results of the investigation revealed the presence of
      proteins, carbohydrates, alpha-keto acids, and lipophilic biosurfactants,
      particularly extracellular pigments, enriched within stable foams. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618848
TI  - Catabolic control of hybridoma cells by glucose and glutamine limited fed batch
      cultures.
AB  - Substrate limited fed batch cultures were used to study growth and overflow
      metabolism in hybridoma cells. A glucose limited fed batch, a glutamine limited
      fed batch, and a combined glucose and glutamine limited red batch culture were
      compared with batch cultures. In all cultures mu reaches its maximum early during
      growth and decreases thereafter so that no exponential growth and decreases
      thereafter so that no exponential growth rate limiting, although the glutamine
      concentration (>0.085mM) was lower than reported K(s) vales and glucose was below
      0.9mM; but some other nutrients (s) was the cause as verified by simulations.
      Slightly more cells and antibodies were produced in the combined fed batch
      compared with the batch culture. The specific rates for consumption of glucose
      and glutamine were dramatically influenced in fed batch cultures resulting in
      major metabolic changes. Glucose limitation decreased lactate formation, but
      increased glutamine consumption and ammonium formation. Glutamine limitation
      decreased ammonium and alanine formation of lactate, alanine, and ammonium was
      negligible in the dual-substrate limited fed batch culture. The efficiency of the
      energy metabolism increased, as judged by the increase in the cellular yield
      coefficient for glucose by 100% and for glutamine by 150% and by the change in
      the metabolic ratios lac/glc, ala/ln, and NH(x)/ln, in the combined fed culture.
      The data indicate that a larger proportion of consumed glutamine enters the TCA
      cycle through the glutamate dehydrogenase pathway, which releases more energy
      from glutamine than the transamination pathway. We suggest that the main reasons
      for these changes are decreased uptake rates of glucose and glutamine, which in
      turn lead to a reduction of the pyruvate pool and a restriction of the flux
      through glutaminase and lactate dehydrogenase. There appears to be potential for
      further cell growth in the dual-substrate-limited fed batch culture as judged by
      a comparison of mu in the different cultures. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618849
TI  - Closed-loop control of fed-batch cultures of recombinant Escherichia coli using
      on-line HPLC.
AB  - This article describes a fully automated system for the on-line monitoring and
      closed-loop control of a fed-batch fermentation of recombinant Escherichia coli,
      and presents two case studies of its used in limiting production of unwanted
      byproducts such as acetic in fed-batch fermentations. The system had two
      components. The first components, on-line monitoring, comprised an aseptic
      sampling device, a microcentrifuge, and HPLC System. These instruments removed a
      Sample from a fermentor, spun it at high speed to separate solid and liquid
      components, and then automatically injected the supernatant onto an HPLC column
      for analysis. The second component consisted of control algorithms programmed
      using the LabView visual programming environment in a control computer that was
      linked via a remote components were linked so that results from the on-line HPLC
      were captured and used by the control algorithm was designed to demonstrate
      coarse feedback control to confirm the operability of the controller. The second
      case study showed how the system could be used in a more sophisticated feedings
      strategy providing fine control and limiting acetate concentration to a low level
      throughout the fermentation. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618850
TI  - Recovery of proteins and amino acids from reverse micelles by dehydration with
      molecular sieves.
AB  - A new method is presented to precipitate proteins and amino acids from reverse
      micelles by dehydrating the micelles with molecular sieves. Nearly complete
      precipitation is demonstrated for alpha-chymotrypsin, cytochromec, and trytophan
      from 2-ethylhexyl sodium sulfosuccinate (AOT)/isooctane/water reverse micelle
      solutions. The products precipitate as a solid powder, which is relatively free
      of surfactant. The method does not require any manipulation of pH, ionic
      strength, temperature, pressure, or solvent composition, and is applicable over a
      broad range of these properties. This general approach is compared with other
      techniques. This general approach is compared with other techniques for the
      recovery of biomolecules from reverse micelles. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618851
TI  - Stoichiometric model of the aerobic metabolism of the biological phosphorus
      removal process.
AB  - In the aerobic phase of the biological phosphorus removal process, poly-beta
      hydroxybutyrate, produced during anaerobic conditions, is used for cell growth,
      phosphate uptake, and glycogen formation. A metabolic model of this process has
      been developed. The yields for growth, polyphosphate and glycogen formation are
      quantified using the coupling of all these conversions to the oxygen consumption.
      The uptake of phosphate and storage as polyphosphate is shown to have a direct
      effect on the observed oxygen consumption in the aerobic phase. The overall
      energy requirements for the P-metabolism are substantial: 25% of the acetate
      consumed during anaerobic conditions and 60% of the oxygen consumptions is used
      for the synthesis of polyphosphate and glycogen. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618852
TI  - New catalytic properties of monoamine oxidase immobilized in Langmuir-blodgett
      films with amphiphilic polyelectrolytes.
AB  - Langmuir-Blodgett (LB) films of monoamine oxidase (MAO) have been formed on the
      surface f a polypropylene membrane using amphiphilic polyelectrolytes. The enzyme
      activity of such protein-polyelectrolyte films was measured by a Clark
      electrodes. It was shown that in LB films thus formed the use of amphiphilc
      polyelectrolytes, MAO activity was higher than in polyelectrolyte-free LB films.
      Immobilization of MAO with branched polyethylenimine modified on 12% by
      laurylchain led to pronounced changes in its catalytic properties. The dependence
      of the enzyme's kinetic parameters on amphiphilic polyelectrolyte structures was
      discussed. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618853
TI  - Efficient Hydrogen photoproduction by synchronously grown cells of a marine
      cyanobacterium, Synechococcus sp. Miami BG 043511, under high cell density
      conditions.
AB  - The capability of hydrogen photoproduction under high cell density conditions was
      examined using synchronously grown cells of nitrogen-fixing Synechococcus sp.
      Miami BG 043511. Optimum hydrogen yield was obtained when vessels (25 ml)
      contained 0.2 to 0.3 mg chlorophyll (a) in 3-mL cell suspension. During a 24-h
      incubation period, an initial phase of hydrogen and carbon dioxide production and
      a subsequent phase of carbon dioxide uptake and oxygen accumulated as major
      products after 24 h. after the initial 24-h. After the initial 24-h incubation,
      as high as 7.4 and 3.7 L (at standard condition) of hydrogen and oxygen,
      respectively, accumulated in vessels with 22-ml gas phase. This indicated that
      the pressure in the flask increased to 1.5 atmosphere. Energy conversion
      efficiency based on photosynthetically active radiation (25 W/m(2)) was about
      2.6%. However, increased pressure somehow reduced the duration of hydrogen
      production. Duration of hydrogen and oxygen production was prolonged by
      periodical (24-h interval) gas replacement during incubation. (c) 1994 John Wiley
      & Sons, Inc.

PMID- 18618854
TI  - DSC and protein-based time-temperature integrators: Case study of alpha-amylase
      stabilized by polyols and/or sugar.
AB  - Differential scanning calorimetry (DSC) was used as a tool for rapid assay of the
      thermostability of two Bacillus sp. alpha-amylases and horseradish peroxidase as
      a function of the concentration of glycerol, sorbitol, and sucrose. In this
      screening study, the DSC peak temperature proved to be a good measure of protein
      thermostability. By means of isothermal heating experiments, the kinetics of heat
      decay of B. amyloliquefaciens alpha-amylase were studied by following the course
      of the DSC peak area (heat exchange (DeltaH/wt)) as a function of time. The high
      stability of this enzyme in the presence of polyolic alcohols or carbohydrates
      allowed working at temperatures as high as 127 degrees C. The results of this
      study can have particular relevance with regard to research on and development of
      protein-based time-temperature integrators (TTls) for evaluating heat
      pasteurization or sterilization treatments of foods or pharmaceutical products.
      The use of the DSC peak area (DeltaH.wt) as TTI-response was validated in
      experiments with a time-variable temperature profile. Finally, it was shown how
      the results of such non-isothermal experiments can even be used for (re-)
      estimation of the protein decay kinetic parameters (k, E(A)). (c) 1994 John Wiley
      & Sons, Inc.

PMID- 18618855
TI  - Knowledge, attitude and willingness of Nigerian physiotherapists to provide care
      for patients living with Acquired Immunodeficiency Syndrome.
AB  - BACKGROUND AND PURPOSE: Adequate knowledge, positive attitude, and willingness to
      provide services are important factors in rendering competent and compassionate
      care to patients living with Acquired Immunodeficiency Syndrome (AIDS).
      Inadequate knowledge and poor attitude could exclude the application of the
      principles of logic and scientific methods to the practice of physiotherapy, and
      could result in fragmented care, with a potentially negative impact on treatment
      outcome and patient satisfaction. The purpose of this study was (1) to
      investigate the Nigerian physiotherapists' global knowledge, attitude and
      willingness to provide care for patients living with AIDS (PLWA), and to (2)
      determine the relationship between socio-demographic variables and previous
      encounter with PLWA, and physiotherapists' knowledge, attitude and willingness to
      care for AIDS survivors. METHODS: Using a 90-item two-part questionnaire that
      elicited sociodemographic and previous AIDS encounter information, and also
      assessed knowledge, attitude and willingness to provide care to PLWA,
      physiotherapists (N = 131) practicing in Nigeria were surveyed. RESULTS: Overall,
      the physiotherapists showed unsatisfactory knowledge about AIDS, harbored
      negative attitude towards PLWA, and some were unwilling to provide care for PLWA.
      Previous experience caring for PLWA influenced their attitude, and modest but
      positive relationships were found between knowledge and attitude and between
      attitude and willingness. CONCLUSION: The study underscores the need to address
      Nigerian physiotherapists' working knowledge deficits and negative attitudes to
      PLWA. A comprehensive AIDS education that would assist clinicians in exploring
      their attitude, stereotype and bias against PLWA is warranted.

PMID- 18618858
TI  - Letter 1: re: Management of acute gallbladder disease in England (Br J Surg 2008;
      95: 472-476).

PMID- 18618859
TI  - Letter 2: re: Management of acute gallbladder disease in England (Br J Surg 2008;
      95: 472-476).

PMID- 18618860
TI  - Epigenetic regulation.

PMID- 18618862
TI  - Letter 3: re: Management of acute gallbladder disease in England (Br J Surg 2008;
      95: 472-476).

PMID- 18618863
TI  - Probiotics in acute pancreatitis.

PMID- 18618864
TI  - Assessment of publication bias for the surgeon scientist.
AB  - BACKGROUND: Publication bias occurs when statistically non-significant (negative)
      findings are not published. It can profoundly affect the results of systematic
      reviews and meta-analyses. METHODS: Qualitative and quantitative methods of
      detecting publication bias are described, including their advantages and
      disadvantages. RESULTS AND CONCLUSION: Accepted quality standards for the
      reporting of meta-analyses recommend assessment of publication bias, but
      currently there is no uniform standard for reporting. Quantitative methods are
      being used with increasing frequency. Authors should take steps to minimize
      publication bias, and use both qualitative and quantitative assessment methods to
      determine whether it is present.

PMID- 18618865
TI  - Application of nitric oxide and carbon monoxide in a model of renal preservation.
AB  - BACKGROUND: Nitric oxide and carbon monoxide exert vasodilatory effects that
      minimize ischaemia-reperfusion injury. An isolated porcine kidney model was used
      to assess the effects of administering the nitric oxide donor sodium
      nitroprusside (SNP) and carbon monoxide-releasing molecule (CORM) 3 during a
      period of warm preservation followed by reperfusion. METHODS: Kidneys were
      perfused under warm preservation conditions after 10 min of warm ischaemia and 16
      h of cold storage in four groups: SNP, control, CORM-3 and inactive CORM-3
      (inactive control). Renal function and viability were assessed. RESULTS: SNP and
      CORM-3 increased renal blood flow (RBF) during warm preservation (P = 0.014).
      After reperfusion, RBF was significantly improved in the CORM-3 group compared
      with the control group (P = 0.019). The reduction in creatinine clearance was
      significantly less in the CORM-3 group than in the inactive CORM-3 group (P =
      0.021), and serum creatinine levels were significantly lower (P = 0.029). There
      was a negative correlation between RBF during warm preservation and functional
      parameters during reperfusion (creatinine concentration: r(s) = - 0.722, P <
      0.001; sodium excretion: r(s) = - 0.912, P < 0.001). CONCLUSION: The beneficial
      vasodilatory effects of CORM-3 during warm preservation improved renal function
      during reperfusion; SNP exerted similar, although less pronounced, effects.

PMID- 18618866
TI  - Re: Peritoneal adhesions (Br J Surg 2008; 95: 271-272).

PMID- 18618869
TI  - Fates of genetically engineered haematopoietic and mesenchymal stem cell grafts
      in normal and injured rat hearts.
AB  - There is an ongoing debate on the potential of adult stem cells as adjuvant
      therapy for patients with heart disease. The aim of our study was to evaluate the
      use of bone marrow (BM)-derived stem cells for cardiac cell and gene therapy in
      normal and ischaemia-injured rat hearts. Haematopoietic (HSCs) and mesenchymal
      stem cells (MSCs) were purified from the BM of adult rats and labelled by: (a)
      genetic transduction of the green fluorescent protein (GFP) using an
      oncoretroviral vector; (b) incorporation of the fluorescent dye PKH26 into the
      cell membrane; and (c) incorporation of bromodeoxyuridine into the chromosomal
      nucleic acid. Cells were directly injected into the beating heart (normal and
      shortly after coronary ligation). Retention of HSCs was--irrespective of the
      ischaemic injury--about 5% on day 3, and < 1% on days 10 and 28. Survival of MSCs
      was approximately 10-15% on day 3, but also < 5% at the later time points. Vector
      mediated GFP expression was rapidly silenced after day 3. There was considerable
      tissue damage around the injection site. Transplanted cells did not migrate from
      the injection site. We did not observe phenotypical changes of the transplanted
      stem cells into cardiac or vascular cells.

PMID- 18618870
TI  - Meta-analysis of the effect of warm humidified insufflation on pain after
      laparoscopy.
AB  - BACKGROUND: Studies on the use of warmed and humidified insufflation (WHI) in
      laparoscopic abdominal procedures to reduce pain have been inconclusive owing to
      small sample sizes. METHODS: An electronic database search identified all
      randomized controlled trials (RCTs) on adults undergoing elective laparoscopic
      abdominal surgery under general anaesthesia in which the exposure group had WHI
      and the control group had standard cold and dry carbon dioxide. The outcome
      measure was pain by visual analogue score or morphine usage. RESULTS: Seven RCTs
      were included. Patients in the WHI group experienced a significant reduction in
      pain score at 6 h (P = 0.006), 1 day (P = 0.010) and 3 days (P < 0.001) after
      operation, and in morphine usage on day 2 (P = 0.040). CONCLUSION: WHI reduces
      pain after laparoscopy.

PMID- 18618871
TI  - Re: Antiangiogenic therapy and surgical practice (Br J Surg 2008; 95: 281-293).

PMID- 18618873
TI  - Head-to-tail interactions in tyrosine/benzophenone dyads in the ground and the
      excited state: NMR and laser flash photolysis studies.
AB  - The formation of head-to-tail contacts in de novo synthesized
      benzophenone/tyrosine dyads, bp logical sum Tyr, was probed in the ground and
      excited triplet state by NMR techniques and laser flash photolysis, respectively.
      The high affinity of triplet-excited ketones towards phenols was used to trace
      the geometric demands for high reactivity in the excited state. A retardation
      effect on the rates with increasing hydrogen-bond-acceptor ability of the solvent
      is correlated with ground-state masking of the phenol. In a given solvent the
      efficiencies of the intramolecular hydrogen-atom-transfer reaction depend
      strongly on the properties of the linker: rate constants for the intramolecular
      quenching of the triplet state cover the range of 10(5) to 10(8) s(-1). The
      observed order of reactivity correlates to a) the probability of close contacts
      (from molecular-dynamics simulations) and b) the extent of the electronic overlap
      between the pi systems of the donor and acceptor moieties (from NMR). A broad
      survey of the NMR spectra in nine different solvents showed that head-to-tail
      interactions between the aromatic moieties of the bp logical sum Tyr dyads
      already exist in the ground state. Favourable aromatic-aromatic interactions in
      the ground state appear to correspond to high excited-state reactivity.

PMID- 18618874
TI  - Synthesis, surface modifications, and size-sorting of mixed nickel-zinc ferrite
      colloidal magnetic nanoparticles.
AB  - We report on the spontaneous covalent growth of monomolecular adlayers on mixed
      nickel-zinc nanoferrite colloidal suspensions (ferrofluids). Synthesized
      nanoparticles were subjected to surface modification by means of acid chloride
      chemistry, leading to the formation of covalent bonds between the hydroxy groups
      at the nanoparticle surface and the acid chloride molecules. This procedure can
      be easily tailored to allow for the formation of adlayers containing both
      hydrophobic and hydrophilic regions stacked at predetermined distances from the
      magnetic core, and also providing the nanoferrites with functional carboxy groups
      capable of further modifications with, for example, drug molecules. Here,
      fluorophore aminopyrene molecules were bound to such modified nanoferrites
      through amide bonds. We also used the same chemistry to modify the surface with
      covalently bound long-chain palmitoyl moieties, and for comparison we also
      modified the nanoferrite surface by simple adsorption of oleic acid. Both
      procedures made the surface highly hydrophobic. These hydrophobic colloids were
      subsequently spread on an aqueous surface to form Langmuir monolayers with
      different characteristics. Moreover, since uniformity of size is crucial in a
      number of applications, we propose an efficient way of sorting the magnetic
      nanoparticles by size in their colloidal suspension. The suspension is
      centrifuged at increasing rotational speed and the fractions are collected after
      each run. The mean size of nanoferrite in each fraction was measured by the
      powder X-ray diffraction (PXRD) technique.

PMID- 18618875
TI  - Rationally designed pincer-type heck catalysts bearing aminophosphine
      substituents: Pd IV intermediates and palladium nanoparticles.
AB  - The aminophosphine-based pincer complexes [C6H3-2,6-(XP(piperidinyl)2)2Pd(Cl)]
      (X=NH 1; X=O 2) are readily prepared from cheap starting materials by sequential
      addition of 1,1',1''-phosphinetriyltripiperidine and 1,3-diaminobenzene or
      resorcinol to solutions of [Pd(cod)(Cl)2] (cod=cyclooctadiene) in toluene under
      N2 in "one pot". Compounds 1 and 2 proved to be excellent Heck catalysts and
      allow the quantitative coupling of several electronically deactivated and
      sterically hindered aryl bromides with various olefins as coupling partners at
      140 degrees C within very short reaction times and low catalyst loadings.
      Increased reaction temperatures also enable the efficient coupling of olefins
      with electronically deactivated and sterically hindered aryl chlorides in the
      presence of only 0.01 mol % of catalyst. The mechanistic studies performed rule
      out that homogeneous Pd 0 complexes are the catalytically active forms of 1 and
      2. On the other hand, the involvement of palladium nanoparticles in the catalytic
      cycle received strong experimental support. Even though pincer-type Pd IV
      intermediates derived from 1 (and 2) are not involved in the catalytic cycle of
      the Heck reaction, their general existence as reactive intermediates (for
      example, in other reactions) cannot be excluded. On the contrary, they were shown
      to be thermally accessible. Compounds 1 and 2 show a smooth halide exchange with
      bromobenzene to yield their bromo derivatives in DMF at 100 degrees C.
      Experimental observations revealed that the halide exchange most probably
      proceeded via pincer-type Pd IV intermediates. DFT calculations support this
      hypothesis and indicated that aminophosphine-based pincer-type Pd IV
      intermediates are generally to be considered as reactive intermediates in
      reactions with aryl halides performed at elevated temperatures.

PMID- 18618876
TI  - One-pot organocatalytic domino Michael/alpha-alkylation reactions: direct
      catalytic enantioselective cyclopropanation and cyclopentanation reactions.
AB  - The development of one-pot organocatalytic domino Michael/alpha-alkylation
      reactions between bromomalonates or bromoacetoacetate esters and alpha,beta
      unsaturated aldehydes is presented. The chiral-amine-catalyzed reactions with
      bromomalonates as substrates give access to the corresponding 2
      formylcyclopropane derivatives in high yields with excellent diastereoselectivity
      and up to 99 % ee. The catalytic domino Michael/alpha-alkylation reactions
      between 4-bromo-acetoacetate and enals provide a route for the synthesis of
      functionalized cyclopentanones in good to high yields with 93-99 % ee. The
      products from the organocatalytic reactions were also reduced with high
      diastereoselectivity to the corresponding cyclopropanols and cyclopentanols,
      respectively. Moreover, one-pot combinations of amine and heterocyclic carbene
      catalysis (AHCC) enabled the highly enantioselective synthesis of beta-malonate
      esters (91-97 % ee) from the reaction between bromomalonates and enals. The
      tandem catalysis included the catalytic domino reaction followed by catalytic in
      situ chemoselective ring-opening of the 2-formylcyclopropane intermediates.

PMID- 18618877
TI  - Dependence of enantioselectivity on the ligand/metal ratio in the asymmetric
      Michael addition of indole to benzylidene malonates: electronic influence of
      substrates.
AB  - Simple bis(oxazoline) ligands, especially azabis(oxazolines), can promote the
      copper(II)-catalyzed Michael addition of indoles to benzylidene malonates with up
      to >99 % ee (ee=enantiomeric excess), provided that the ligand/metal ratio is
      tuned meticulously with particular regard to the electronic properties of the
      substrate. Despite a common paradigm followed in many asymmetric catalyses, an
      excess of chiral ligand is not always beneficial. In fact any excess of ligand
      has to be avoided to reach excellent enantioselectivities when electron-rich
      benzylidene malonates are used. On the contrary, malonates carrying an electron
      withdrawing group require an excess of ligand for an optimum ee value. A
      correlation of optical yields versus the sigma(I) values of several para
      substituents shows a sigmoid trajectory. In the presence of an additive, such as
      triflate, the significance of the ligand/metal ratio vanishes and very good
      enantioselectivities are achieved at any rate--no matter whether electron
      donating or withdrawing substituents are present.

PMID- 18618878
TI  - Infrared multiple-photon dissociation mechanisms of peptides of glycine.

PMID- 18618879
TI  - Extreme rate acceleration by axial thiolate coordination on the isomerization of
      endoperoxide catalyzed by iron porphyrin.

PMID- 18618880
TI  - A practical, self-catalytic, atomic layer deposition of silicon dioxide.

PMID- 18618882
TI  - Surface-enhanced Raman spectroscopy for trace arsenic detection in contaminated
      water.

PMID- 18618881
TI  - An electron-transfer series of high-valent chromium complexes with redox non
      innocent, non-heme ligands.

PMID- 18618883
TI  - Pronounced steric effects of substituents in the nazarov cyclization of aryl
      dienyl ketones.

PMID- 18618884
TI  - Hybrid alphagamma polypeptides: structural characterization of a C12/C10 helix
      with alternating hydrogen-bond polarity.

PMID- 18618885
TI  - A cationic cyclic phosphorus(III) azide.

PMID- 18618886
TI  - Complete deracemization by attrition-enhanced ostwald ripening elucidated.

PMID- 18618887
TI  - Palladium-catalyzed amination of aryl mesylates.

PMID- 18618888
TI  - Electronic and vibrational spectroscopy of 1-methylthymine and its water
      clusters: the dark state survives hydration.
AB  - Electronic and vibrational gas phase spectra of 1-methylthymine (1MT) and 1
      methyluracil (1MU) and their clusters with water are presented. Mass selective
      IR/UV double resonance spectra confirm the formation of pyrimidine-water clusters
      and are compared to calculated vibrational spectra obtained from ab initio
      calculations. In contrast to Y. He, C. Wu, W. Kong; J. Phys. Chem. A, 2004, 108,
      94 we are able to detect 1MT/1MU and their water clusters via resonant two-photon
      delayed ionization under careful control of the applied water-vapor pressure. The
      long-living dark electronic state of 1MT and 1MU detected by delayed ionization,
      survives hydration and the photostability of 1MT/1MU cannot be attributed solely
      to hydration. Oxygen coexpansions and crossed-beam experiments indicate that the
      triplet state population is probably small compared to the (1)n pi* and/or hot
      electronic ground state population. Ab initio theory shows that solvation of 1MT
      by water does not lead to a substantial modification of the electronic relaxation
      and quenching of the (1)n pi* state. Relaxation pathways via (1)pi pi*(1)-n
      pi*(1) and (1)pi pi*-S(0) conical intersections and barriers have been
      identified, but are not significantly altered by hydration.

PMID- 18618889
TI  - Variable-temperature infrared spectroscopy studies on the thermodynamics of CO
      adsorption on the zeolite Ca-Y.
AB  - Variable temperature FT-IR spectroscopy (in the range of 298-380 K) is used to
      study the thermodynamics of formation of Ca(2+)...CO carbonyl species upon CO
      adsorption on the faujasite-type zeolite Ca-Y, and also the (temperature
      dependent) isomerization equilibrium between carbonyl and isocarbonyl
      (Ca(2+)...OC) species. The standard enthalpy and entropy changes involved in
      formation of the monocarbonyl species resulted to be DeltaH(0)=-50.3 (+/-0.5) kJ
      mol(-1) and DeltaS(0)=-186 (+/-5) J mol(-1) K(-1), respectively. Isomerization of
      the (C-bonded) Ca(2+)...CO carbonyl to yield the (O-bonded) Ca(2+)...OC
      isocarbonyl involves an enthalpy change DeltaH(iso)(0)=+11.4 (+/-1.0) kJ mol(-1).
      These results are compared with previously reported data for the CO/Sr-Y system;
      and also, a brief analysis of enthalpy-entropy correlation for CO adsorption on
      zeolites and metal oxides is given.

PMID- 18618890
TI  - C-H bonds with a positive dipole gradient can form blue-shifting hydrogen bonds:
      the complex of halothane with methyl fluoride.
AB  - The complex of halothane (CF(3)CBrClH) with ([D(3)])methyl fluoride is
      investigated theoretically by means of ab initio calculations at the MP2/6
      311++G(d,p) level and experimentally by infrared spectroscopy of solutions in
      liquid krypton. The complexation energy is calculated to be -12.5 kJ mol(-1). The
      dipole moment of halothane monomer as a function of the C-H stretching coordinate
      is calculated with different methodologies and the value of (partial
      differential(mu)/partial differential(Q(1)))0 is found to be positive. In the
      spectra, formation of a 1:1 complex is observed. The standard complexation
      enthalpy is measured to be -8.4(2) kJ mol(-1). The C-H stretching vibration of
      halothane shows a blueshift of +15.4 cm(-1) on complexation, and its infrared
      intensity ratio epsilon(complex)/epsilon(monomer) is found to be 1.39(7). The
      frequency shift is analyzed by a Morokuma analysis, and the infrared intensities
      are rationalized by using a model which includes the mechanical and electrical
      anharmonicity of the C-H stretching vibration.

PMID- 18618891
TI  - The anthelmintic activity of the cyclotides: natural variants with enhanced
      activity.
AB  - The cyclotides are a family of backbone-cyclised cystine-knot-containing peptides
      from plants that possess anthelmintic activity against Haemonchus contortus and
      Trichostrongylus colubriformis, two important gastrointestinal nematode parasites
      of sheep. In the current study, we investigated the in vitro effects of newly
      discovered natural cyclotides on the viability of larval and adult life stages of
      these pests. The natural variants cycloviolacin O2, cycloviolacin O3,
      cycloviolacin O8, cycloviolacin O13, cycloviolacin O14, cycloviolacin O15, and
      cycloviolacin O16 extracted from Viola odorata showed up to 18-fold greater
      potency than the prototypic cyclotide kalata B1 in nematode larval development
      assays. Cycloviolacin O2 and cycloviolacin O14 were significantly more potent
      than kalata B1 in adult H. contortus motility assays. The lysine and glutamic
      acid residues of cycloviolacin O2, the most potent anthelmintic cyclotide, were
      chemically modified to investigate the role of these charged residues in
      modulating the biological activity. The single glutamic acid residue, which is
      conserved across all known cyclotides, was shown to be essential for activity,
      with a sixfold decrease in potency of cycloviolacin O2 following methylation. The
      three lysine residues present in cycloviolacin O2 were acetylated to effectively
      mask the positive charge, resulting in a 18-fold decrease in anthelmintic
      activity. The relative anthelmintic activities of the natural variants assayed
      against nematode larvae correlated with the number of charged residues present in
      their sequence.

PMID- 18618892
TI  - Synthesis, characterization, and application of cationic water-soluble
      oligofluorenes in DNA-hybridization detection.
AB  - A simple and efficient approach was developed for the synthesis of a series of
      cationic water-soluble oligofluorenes up to a chain length of a heptamer.
      Bromoalkyl-substituted fluorenyl boronic esters as the key intermediates were
      synthesized by using a modified Miyaura reaction. With an increasing number of
      repeat units (trimer to hexamer), the size-specific oligomers have shown
      redshifts in both the absorption and emission maxima. The emission maximum
      reaches the limit for the hexamer in both water and buffer solution. The quantum
      yields of the oligomers decreased with increased oligomer size in water. Both
      fluorescence quenching of the oligomers by 9,10-anthraquinone-2,6-disulfonate and
      the fluorescence resonance energy transfer experiments with the oligomers as the
      donor and fluorescein (Fl)-labeled double-stranded DNA (dsDNA-Fl) as the acceptor
      revealed the chain-length-dependent behavior. The Stern-Volmer quenching constant
      increased with the molecular size, whereas the highest donor-sensitized Fl
      emission was observed for the hexamer. These size-specific oligomers also served
      as a model to study the structure-property relationships for cationic
      polyfluorenes.

PMID- 18618893
TI  - Risk factors for transient vocal cord palsy after thyroidectomy.
AB  - BACKGROUND: Transient recurrent laryngeal nerve palsy affects to 5-10 per cent of
      patients after extracapsular thyroidectomy. This prospective study assessed the
      impact of surgical injury and extralaryngeal branching of the inferior laryngeal
      nerve (ILN) on vocal cord dysfunction (VCD). METHODS: Total thyroidectomy or
      lobectomy was performed in 188 patients, with 302 ILNs at risk. The anatomy of
      the ILN and degree of injury to the nerve, based on the Laryngeal Nerve Injury
      Score (LNIS), were recorded. Fibreoptic laryngoscopy was performed a mean(s.d.)
      of 10.6(4.1) days after thyroidectomy. RESULTS: Some 37.4 per cent of ILNs showed
      extralaryngeal branching. In all, 10.9 per cent of patients developed VCD; 4.3
      per cent had paresis and 6.6 per cent paralysis. All paretic and all but one
      paralytic cords recovered fully after 61(17) days. VCD was more frequently
      associated with branched than non-branched ILNs (15.8 versus 8.1 per cent; P =
      0.022). Injuries were more common in branched nerves (mean(s.e.m.) total LNIS
      0.94(0.08) versus 0.51(0.05); P < 0.001). Branched nerves were more likely to be
      associated with VCD (odds ratio 2.2 (95 per cent confidence interval 1.1 to
      4.5)). CONCLUSION: Branched ILNs suffer more surgical injuries and are twice as
      likely to be associated with VCD.

PMID- 18618894
TI  - Re: Randomized clinical trial comparing day-care open haemorrhoidectomy under
      local versus general anaesthesia (Br J Surg 2008; 95: 555-563).

PMID- 18618895
TI  - New evidence for the molecular-chemical diversity of potato plant rhizodeposits
      obtained by pyrolysis-field Ionisation mass spectrometry.
AB  - INTRODUCTION: Detailed descriptions of the molecular-chemical diversity in plant
      rhizodeposits are scarce. The vast majority of our knowledge is derived from a
      priori methods of analysis, such as GC-MS and HPLC. OBJECTIVE: To analyse the
      composition of rhizodeposits from the potato cultivar Solanum tuberosum L. cv.
      Albatros by pyrolysis -field ionisation mass spectrometry (Py-FIMS) and to
      explain differences in relation to plant growth stage and photoperiod.
      METHODOLOGY: Potato (Solanum tuberosum L.) plants were grown in non-sterile,
      native soil under controlled environmental conditions (plant chamber).
      Rhizodeposit samples were collected by leaching during two different growth
      stages and after the physiological day- and night-cycle. All leachate samples
      were investigated by Py-FIMS. Mass spectrometric data were evaluated by
      multivariate statistics. RESULTS: Screening of the rhizodeposits by Py-FIMS
      revealed a broad range of m/z signals. Low-molecular-weight substances of m/z 15
      56 (8.1-18.6%), alkylaromatics (12.0-15.9%), phenols and lignin monomers (8.8
      13.1%) and carbohydrates (6.0-11.2%) comprised the largest proportions of total
      ion intensity (TII). Mass signals with significantly different abundance at the
      various sampling dates were assigned to compound classes of carbohydrates,
      phenols and lignin monomers, lignin dimers, lipids, N-containing compounds,
      sterols, peptides and free fatty acids; these were supplemented by marker signals
      for N-acetylmuramic acid from bacterial cell walls and signal molecules for the
      regulation of secondary pathways such as 4-hydroxycinnamic acid and linolenic
      acid. CONCLUSION: Py-FIMS was well suited to detect the molecular-chemical
      diversity of potato plant rhizodeposits and, compared with traditional a priori
      analytical methods, provided detailed evidence for significant differences in the
      composition of rhizodeposits depending on growth stage and diurnal period.

PMID- 18618896
TI  - Assessment of different sample processing procedures applied to the determination
      of melatonin in plants.
AB  - INTRODUCTION: Melatonin, an indoleamine well known in vertebrates and
      structurally related to other important substances such as tryptophan or indole-3
      acetic acid, is also present in the plant kingdom although its specific
      function(s) remain to be established. The emerging field of melatonin studies in
      plants has progressed very slowly, mainly due to the problems associated with
      melatonin quantification in plants. OBJECTIVE: Two commonly used procedures for
      plant samples are compared. The analytical characteristics of both procedures are
      quantitatively presented using different solvents and small amounts of fresh
      biological material, and the respective recovery rates and quantitative limits
      are presented. Some improvements are suggested. METHODOLOGY: Two different sample
      extraction procedures were compared: a direct-sample extraction (DSE) and a
      homogenised- sample extraction (HSE). Melatonin was then determined in the
      respective plant samples by HPLC with fluorescence detection. RESULTS: Using the
      DSE procedure, more than 94% melatonin was recovered from standard solutions,
      whereas levels higher than 93% were recovered from the spiked plant samples, with
      little difference between ethyl acetate and chloroform extractions. In the case
      of HSE, the recoveries of melatonin were approximately half and never higher than
      55%. The ultrasonic treatment proposed in the DSE procedure showed different
      levels of efficiency (2-20%), depending on the sample. CONCLUSION: This study has
      established that, with the direct sample extraction procedure, higher recovery
      rates are obtained both in standard solutions and in plant samples. The
      straightforwardness and reproducibility of the extraction procedure is
      accompanied by the high sensitivity obtained with fluorescence detection.

PMID- 18618897
TI  - Initial experience with a multimodal enhanced recovery programme in patients
      undergoing liver resection.
AB  - BACKGROUND: Accelerated recovery from surgery has been achieved when patients are
      managed within a multimodal Enhanced Recovery After Surgery (ERAS) protocol. This
      study evaluated the benefit of an ERAS programme for patients undergoing liver
      resection. METHODS: The ERAS protocol of epidural analgesia, early oral intake
      and early mobilization was studied prospectively in a consecutive series of 61
      patients. Outcomes were compared with those in a consecutive series of 100
      patients who underwent liver resection before the start of the study. Endpoints
      were postoperative length of hospital stay, postoperative resumption of oral
      intake, readmissions, morbidity and mortality. RESULTS: Fifty-six patients (92
      per cent) in the ERAS group tolerated fluids within 4 h of surgery and a normal
      diet on day 1 after surgery. Median hospital stay, including readmissions, was
      6.0 days compared with 8.0 days in the control group (P < 0.001). There were no
      significant differences in rates of readmission (13 and 10.0 per cent
      respectively), morbidity (41 and 31.0 per cent) and mortality (0 and 2.0 per
      cent) between ERAS and control groups. CONCLUSION: The ERAS fast-track protocol
      is safe and effective for patients undergoing liver resection. It allows early
      oral intake, promotes faster postoperative recovery and reduces hospital stay.

PMID- 18618898
TI  - Breast cancer in young families: a qualitative interview study of fathers and
      their role and communication with their children following the diagnosis of
      maternal breast cancer.
AB  - OBJECTIVE: To explore father-child communication following the diagnosis of
      maternal breast cancer, examine disparities in their understandings of the impact
      of the illness, and identify gaps in their need for support and information.
      METHODS: The design is the qualitative interview study with thematic analysis.
      The interviews were home-based with fathers and children in Oxfordshire, UK. The
      participants were 26 fathers whose partners had early breast cancer and 31 of
      their children aged between 6 and 18 years. RESULTS: Fathers described
      graphically their reaction to news of their partner's breast cancer and their
      attempts to provide support for their partners and maintain normal family life
      for their children. Fathers were keen to reassure and protect children but often
      said that they lacked sufficient information about breast cancer-especially side
      effects of treatments. Fathers sometimes did not recognise the extent of their
      children's distress and some interpreted their children's reactions as 'bad
      behaviour' or 'rudeness'. Children were often acutely aware of the father's
      emotional state, and expressed a wish to protect him. Some fathers would have
      liked an opportunity to talk to a clinician directly about the children but did
      not want to claim clinical time for themselves or their children. CONCLUSION:
      This study suggests that clinicians could improve their care of breast cancer
      patients by being more family-centred. Fathers routinely need more information
      and preparation about the likely impact of the illness and its treatment
      (especially side effects) on the mother, and how children of different ages may
      react to the emotional strain. Clinicians need to be prepared to offer to talk to
      teenagers.

PMID- 18618899
TI  - Antecedents of domain-specific quality of life after colorectal cancer.
AB  - OBJECTIVE: The present study prospectively assessed the influence of medical,
      socio-demographic, psychological, and lifestyle variables on physical,
      social/family, emotional, functional well-being and colorectal cancer-specific
      concerns in a population-based sample of colorectal cancer survivors. METHODS:
      Participants (n=1822) were assessed at 6 and 24 months post-diagnosis. Predictor
      variables assessed at 6 months included socio-demographic and medical variables,
      symptoms/side-effects, body mass index, physical activity, optimism, social
      support, and cancer threat appraisal. Quality of life (QOL) was assessed at 6 and
      24 months post-diagnosis using the Functional Assessment of Cancer Therapy -
      Colorectal (FACT-C). RESULTS: For each QOL subscale and for the overall FACT-C
      scale, 6 month scores were the strongest predictor of QOL scores at 24 months
      post-diagnosis (e.g. beta=0.447, p < 0.001 for overall QOL). Socio-demographic,
      medical, and psychosocial variables, but not lifestyle variables, differentially
      predicted domain specific QOL. Only cancer threat appraisal was associated with
      all five QOL domains. CONCLUSION: Cancer threat appraisal presents as a
      potentially modifiable variable for interventions seeking to improve QOL. Symptom
      management and lifestyle strategies to ameliorate the effects of co-morbidities,
      disease stage and troublesome symptoms such as faecal incontinence on QOL should
      also be included.

PMID- 18618900
TI  - Total synthesis and stereochemical reassignment of tasiamide.
AB  - The total synthesis of a marine acyclic peptide tasiamide and three diastereomers
      was reported for the first time. The synthesis has led to a reassignment of the
      N(alpha)-Me-L-Gln of tasiamide to be N(alpha)-Me-D-Gln, which was supported by 1H
      NMR, 13C NMR, COSY, HMQC, HMBC, and optical rotation.

PMID- 18618901
TI  - Sequential continual reassessment method for two-dimensional dose finding.
AB  - It is common to encounter two-dimensional dose finding in phase I trials, for
      example, in trials combining multiple drugs, or in single-agent trials that
      simultaneously search for the maximum tolerated dose (MTD) and the optimal
      treatment schedule. In these cases, the traditional single-agent dose-finding
      methods are not directly applicable. We propose a simple and adaptive two
      dimensional dose-finding design that can accommodate any type of single-agent
      dose-finding method. In particular, we convert the two-dimensional dose-finding
      trial to a series of one-dimensional dose-finding subtrials along shortened line
      search segments by fixing the dose level of one drug. We then conduct the
      subtrials sequentially. Based on the MTD obtained from the completed one
      dimensional trial, we eliminate the doses that lie outside of the search range
      based on the partial order, and thereby efficiently shrink the two-dimensional
      dose-finding space. The proposed design dramatically reduces the sample size and
      still maintains good performance. We illustrate the design through extensive
      simulation studies motivated by clinical trials evaluating multiple drugs or dose
      and schedule combinations.

PMID- 18618902
TI  - Sedation and antihistamines: an update. Review of inter-drug differences using
      proportional impairment ratios.
AB  - BACKGROUND: The use of antihistamines (AHs) has been associated with cognitive
      and psychomotor impairments, largely caused by the sedative properties of many of
      these drugs. Due to the ambulant nature of the population using AHs, it is
      important to evaluate these effects using standardised methodology and
      psychometric tests. A previous extensive review of the literature collated the
      results of studies of H(1) receptor antagonists to determine the extent to which
      a particular AH produced impairments on a battery of psychometric tests by
      calculating a proportional impairment ratio for each AH. OBJECTIVE: In light of a
      number of major studies published following the previous review, and the
      development of the second and new-generation AHs, the present review aims to add
      to the database and update the review, using the same methodology. RESULTS AND
      CONCLUSION: The newer generation AHs appear to be the least impairing, and the
      first generation, as expected, appear to be the most impairing. There are also
      differences within the AH drug generations. The review highlights the necessity
      to consider the sedating potential of AHs, along with other factors such as
      efficacy, when prescribing AHs to ambulant patients.

PMID- 18618904
TI  - Solids retention time in spherical biofilms in a biofilm airlift suspension
      reactor.
AB  - Fluorescent microparticles were used as tracer beads to measure the dynamics of
      solids in spherical biofilms in a biofilm airlift suspension reactor. Attachment
      to, release from, and penetration into the biofilms of the tracer beads were
      measured. The coverage of the biofilm surface was low and the steady state
      particle concentration on the surface was dependent on the biofilm surface
      characteristics. The measured attachment rate constant was identical in both
      experiments and appeared to be determined by the hydrodynamic conditions in the
      turbulent reactor. The attachment rate was much faster than the release rate of
      the tracer beads and, therefore, the solidsretention time in the biofilm particle
      is not due to a simple reversible adsorption-desorption process. The
      heterogeneity of the distribution oftracer beads on different sectors on the
      biofilm surface decreased duringthe attachment period. Due to random detachment
      processes the heterogeneity of the tracer bead distribution increased during the
      release periodThe tracer beads quickly penetrated into the biofilm and became
      distributed throughout the active layer of the biofilm. The observed penetration
      into biofilms, the nonuniform distribution on the biofilm surface, and the fast
      uptake and slow release of tracer beads cannot be described by a simple model
      based on a reversible adsorption-desorption mechanism, nor withexisting biofilm
      models. These biofilm models, which balance growth and advection assuming a
      uniform biofilm with a homogeneous surface, are inadequate for the description of
      the observed solids retention time in biofilms. Therefore, a new concept of
      biofilm dynamics is proposed, in which formation of cracks and fissures, which
      are rapidly filled with growing biomass, combined with nonuniform local
      detachment, explains the observed fast penetration into the biofilm of tracer
      beads, the long residence time, and the nonuniform distibution of fluorescent
      microparticles. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618905
TI  - Oxygen requirements and mass transfer in hairy-root culture.
AB  - Oxygen mass transfer in clumps of Atropa belladonna hairy roots was investigated
      as a function of root density and external flow conditions. Convection was the
      dominant mechanism for mass transfer into root clumps 3.5 to 5.0 cm in diameter;
      Peclet numbers inside the clumps ranged from 1.4 x 10(3) to 7.1 x 10(4) for
      external superficial flow velocities between 0.4 and 1.4 cm s(-1). Local
      dissolved-oxygen levels and rates of oxygen uptake were measured in aflow chamber
      and in bubble column and stirred bioreactors. When air was used as oxygen source,
      intraclump dissolved-oxygen tensions ranged from90% to 100% air saturation at
      high external flow velocity andlow root density, to less than 20% air saturation
      in dense root clumps. Specific oxygen-uptake rate declined with increasing root
      density. When external boundary layers around individual roots were eliminated
      byforcing liquid through the clumps at superficial velocities between 0.2 and1.0
      cm s(-1), internal dissolved-oxygen tension was maintained at 95% to 100% air
      saturation and rate of oxygen uptake at 1.6 x 10(-6) g g(-1) s(-1) dry weight.
      Liquid culture of single A. belladonna hairy roots was used to investigate the
      effect of dissolved-oxygen tensionon root growth and morphology. Total root
      length and number of root tips increased exponentially at oxygen tensions between
      70% and 100%air saturation. Specific growth rate increased with oxygen tension up
      to 100% air saturation; this result demonstrates that hairy roots aeratedwithout
      oxygen supplementation are likely to be oxygenlimited. No growth occurred at 50%
      air saturation. Growth of hairy roots proceeded with an average length per tip of
      about 1 cm; this value was essentially independent of dissolved-oxygen tension
      between 70% and 100% air saturation. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618906
TI  - Formation of carotenoids by rhodotorula glutinis in whey ultrafiltrate.
AB  - The growth and carotenoid biosynthesis of the yeast Rhodotorula glutinis was
      studied by cocultivation with Lactobacillus helveticus in cheese ultrafiltrate
      containing 3.9% and 7.1% lactose. By growing this mixed culture in a 15-L
      fermentor MBR AG (Switzerland) at an air flow rate of 0.5 L/L min and agitation
      at 220 rpm for 6 days, a total yield of carotenoids of 268 mug/g dry cells
      wasobtained. Carotenoids were formed almost parallel with the cell growth, anda
      maximum production was reached at an early stationary phase. A high-performance
      liquid chromatographic system (HPLC) permitting simultaneous determination of
      major carotenoid pigments was used. The three main pigments (torularhodin, beta
      carotene, and torulene) were formed in Rhodotorula glutinis, and reached a
      maximum concentration as follows: 182.0, 43.9, 23.0 mug,g dry cells. (c) 1994
      John Wiley & Sons, Inc.

PMID- 18618907
TI  - High-density continuous cultures of hybridoma cells in a depth filter perfusion
      system.
AB  - A depth filter perfusion system (DFPS) for animal cell culture was developed and
      its use in continuous highdensity cultures of hybridoma cells was investigated.
      In the DFPS, based on cell immobilization in a cylindrical depth filter matrix,
      cells were easily immobilized and cultivated by simple medium recirculation. The
      cell density in the 20-mum pore size filter matrix reached up to 3 x 10(7)
      cells/mLin less than 10 days. This resulted in a high monoclonal antibody
      productivity of 744 mg/L/day, which was 25-35 times higher than that of
      continuous-suspension cultures using the same cell line. The 20-mum pore filter
      retained more cells than the 30-mum filterin a shorter period. The DFPS provides
      advantages of low-cost set-up, easy operation, and scale-up in the cultures of
      anchorage-independent cells. It also has a high potential for anchorage-dependent
      cell cultures because of its unusually high surface-to-volume ratio of 450-600
      cm(2)/cm(3). (c) 1994 John Wiley & Sons, Inc.

PMID- 18618908
TI  - Multiple product inhibition and growth modeling of clostridium butyricum and
      klebsiella pneumoniae in glycerol fermentation.
AB  - The inhibition potentials of products and substrate on the growth ofClostridium
      butyricum and Klebsiella pneumoniae in the glycerol fermentation are examined
      from experimental data and with a mathematicalmodel. Whereas the inhibition
      potential of externally added and self-produced 1,3-propanediol is essentially
      the same, butyric acid produced by the culture is more toxic than that externally
      added. The same seems to apply for acetic acid. The inhibitory effect of butyric
      acid is due tothe total concentration instead of its undissociated form. For
      acetic acid, it cannot be distinguished between the total concentration and the
      undissociated formThe inhibition effects of products and substrate in the
      glycerol fermentation are irrespective of the strains, and, therefore, the same
      growth model can be used. The maximum product concentrations tolerated (critical
      concentrations C(*) (pi)) are 0.35 g/Lfor undissociated acetic acid, 10.1 g/L for
      total butyric acid, 16.6 g/L for ethanol, 71.4 g/L for 1,3-propanediol, and 187.6
      g/L for glycerol, which are applicable to C. butyricum and K. pneumoniae grown
      under a variety of conditions. For 55 steady-states, which were obtained from
      different types of continuous cultures over a pHrange of 5.3-8.5 and under both
      substrate limitation and substrate excess, the proposed growth model fits the
      experimental data with an average deviation of 17.0%. The deviation of model
      description from experimental values reduces of 11.4% if only the steady-states
      with excessive substrate are considered. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618909
TI  - Evaluation of the hok/sok killer locus for enhanced plasmid stability.
AB  - The effectiveness of the hok/sok plasmid stability locus and mechanism of cloned
      gene loss was evaluated in shake-flask cultures. Addition of the hok/sok locus
      dramitically increasedapparent plasmid segregational stability to the hok/sok(-)
      control. In terms of the number of generations before 10%of the population became
      plasmid-free, segregational stability was increased by 11- to 20-fold in
      different media in the absence of induction of the cloned-gene (hok/sok(+)
      plasmid stable for over 200 generations in all media tested). With constant
      expression of beta-galactosidase in the absence of an tibiotic, the segregational
      stability of the plasmid containing hok/sok was incresed more than 17- to 30-fold
      when beta-galactosidase was expressed at 7-15 wt % of total cell protein.
      Although the hok/sok system stabilized the plasmid well infour different media
      (Luria-Bertani (LB), LB glucose, M9C Trp, and a representative fedbatch medium),
      the ability of hok/sok to maintain the plasmid with induction of the cloned gene
      decreased as the complexity of the media increased. This result is better
      interpreted in terms of the influence of cloned-gene expression on
      plasmidmaintenance; plasmid segregational stability decreased linearly as
      specificbeta-galactosidase activity increased. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618910
TI  - Pilot scale recovery of recombinant annexin V from unclarified escherichia coli
      homogenate using expanded bed adsorption.
AB  - Expanded bed adsorption is a new downstream processing technique forcapture of
      proteins directly from unclarified feedstocks. Expanded bed adsorption reduces
      the number of operations in purification processes by combining clarification,
      concentration, and capture into one operation. It is based on stable fluidization
      and uses adsorbent particles with well-defined size and density distributions,
      together with columns designed to giveeven liquid flow distribution. The bed
      expands as the adsorbent particles are lifted by an upward liquid flow through
      the column. The behavior of the expanded bed is similar to a packed
      chromatography bed due to very little back-mixing of the adsorbent particles. The
      major benefit of using anexpanded bed is that adsorption can be carried out with
      unclarified feedstocks; there is no need for centrifugation or filtration to
      remove cells and debris. When the feedstock is applied, the target protein is
      captured by the adsorbent while cells and debris pass through the column
      unhindered. Washing is performed with the bed in an expanded mode, followed by
      elution of bound protein in a sedimented mode with downward flowDescribed in this
      article is the use of expanded bed adsorption for pilot scale recovery of
      recombinant human placental annexin V from an Escherichia coli ho mogenate. The
      description includes the whole procedure, from small-scale method optimization to
      pilot scale. The recovery of annexin V was approximately 95% at both lab scale
      and pilot scale. During the trials, it was discovered that the expanded bed was
      affected by the biomass content and viscosity of the homogenate. The upper limits
      for these parameters were therefore investigated further. For the E. coli used in
      the application described here, homogenates with biomass dry weightup to 5% and
      viscosities up to 10 mPa s (at a shear rate of 1 s(-1)) worked best. It was,
      however, feasible to use homogenates with dry weight up to 7-8% and viscosities
      up to 50 mPa s (1 s(-1)). (c) 1994 John Wiley & Sons, Inc.

PMID- 18618911
TI  - Production of somatic embryos in a helical ribbon impeller bioreactor.
AB  - Embryogenic cultures of a transformed Eschscholtzia californica cell line were
      carried out in a 11-L helical ribbon impeller bioreactor operated under various
      conditions to evaluate the performance of this equipment for somatic embryo (SE)
      production. All bioreactor cultures produced SE suspensions with maximum
      concentrations at least comparable to those obtained from flask control cultures
      ( approximately 8-13 SE . mL(-;1)). However, an increase of the mixingspeed, from
      60 to 100 rpm, and low sparging rate ( approximately 0.05 VVM, k(L) a
      approximately 6.1 h(-;1)) for dissolved oxygen concentration (DO) control yielded
      poorer quality embryogenic cultures. The negative effects on SE production were
      attributed mainly to the low but excessive shear experienced by the embryogenic
      cells and/or embryoforming aggregates. High DO ( approximately 60% of air
      saturation) conditions favored undifferentrated biomass production and high
      nutrient uptake rates at the expense of the slower SE differentiation process in
      both flask and bioreactor cultures. Too low DO (-5-10%) inhibited biomass and SE
      production. The best production of SE ( approximately 44 SE . mL(-1) or
      approximately 757 SE . g dw(-1) . d(-1)) was achieved by operating the bioreactor
      at 60 rpm while controlling DO at approximately 20%by surface oxygenation only
      (0.05 VVM, k(L) a approximately 1.4 h(-;1)). This production was found to be a
      biomass production/growth-associated process and was mainly limited by the
      availability of extracellular phosphate, magnesium, nitrogen salts, and
      carbohydrates. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618912
TI  - Modification of central metabolic pathway in escherichia coli to reduce acetate
      accumulation by heterologous expression of the bacillus subtilis acetolactate
      synthase gene.
AB  - A novel metabolic engineering technique involving the redirection ofcellular
      carbon fluxes was employed to reduce acetate production in an Escherichia coli
      culture. Metabolic engineering was achieved by cloning E. coli the gene for the
      Bacillus subtilis acetolactate synthase (ALS), an enzyme capable of catalyzing
      the conversion of pyruvate to nonacidic and less harmful species. The
      heterologous expression of the ALS catabolic enzyme in Escherichia coli
      drastically modified the cellular glycolytic fluxes. In particular, acetate
      excretion, which is a common characteristic of E. coli, as well as a
      physiological burden, was minimized. The residual acetate level was kept under
      control and maintained at a level that was below the toxic threshold. The
      expression of the biologically active ALS enzyme in E. coli did not result in any
      detectable changes on either cell growth rate or cell yields. The alternative
      product, acetoin, was shown to be 50 times less harmful than acetate.
      Similarities in the growth pattern of two different E. coli strains, RR1 and
      GJT001, under all cultivation conditions suggested that the ability of ALS to
      reduce acetate accumulation is generic and not strain-specific. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618913
TI  - Effect of modified glucose uptake using genetic engineering techniques on high
      level recombinant protein production in escherichia coli dense cultures.
AB  - Reduction of acetate excretion using a modified cellular glucose uptake rate was
      examined. An Escherichia coli strain bearing a mutationin ptsG, a gene encoding
      enzyme II in glucose phosphotransferase system (PTS), was constructed and
      characterized. The growth rate of the mutant strain was slower than its parent in
      glucose defined medium, butwas not affected in complex medium. Experimental
      results using this mutant strain showed a significant improvement in culture
      performance in simple batch cultivations due to reduced acetate excretion through
      the modified glucose uptake. Both biomass and recombinant protein productivity
      were increased by more than 50% with the ptsG mutant when compared to the parent
      strain. Recombinant protein productivity by the newly constructed strain at a
      level of more than 1.6 g/L was attained consistently in a simple batch
      bioreactor. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618914
TI  - Specific quantification of trichoderma reesei cellulases in reconstituted
      mixtures and its application to cellulase-cellulose binding studies.
AB  - Specific quantifications of the major cellulolytic components of the Trichoderma
      reesei enzyme complex, i.e., endoglucanases I and III and cellobiohydrolases I
      and II, are described and, employing a defined mixture of these four cellulases
      reconstituted according to the composition of the native Trichoderma cellulase
      complex, used to determine the binding of each individual component onto filter
      paper. During substrate degradation by this enzyme mixture, the specific
      adsorption of each individual cellulase gradually increases and no preferential
      binding of one enzyme component in any particular phase of cellulose hydrolysis
      is found. T. reesei cellobiohydrolases I and II admixed with endoglucanases I and
      III represent a "full-value" cellulase system that is capable of degrading
      semicrystalline cellulose efficiently. In comparison with the crude Trichoderma
      enzyme complex, almost identical adsorption properties and similar hydrolytic
      efficiency are found for the reconstituted mixture. (c) 1994 John Wiley & Sons,
      Inc.

PMID- 18618915
TI  - Improved taxol yield by aromatic carboxylic acid and amino acid feeding to cell
      cultures of taxus cuspidata.
AB  - Cell culture of Taxus cuspidata represents an alternative to whole plant
      extraction as a source of taxol and related taxanes. Feeding phenylalanine to
      callus cultures was previously shown to result in increased taxol yields,
      probably due to the involvement of this amino acid as a precursor for the N
      benzoylphenylisoserine side chain of taxol. Inthis study, we have examined the
      effect of various concentrations of phenylalanine, benzoic acid, N
      benzoylglycine, serine, glycine, alanine, and 3-amino-3-phenyl-propionic acid on
      taxol accumulation in 2-year-old cell suspensions of Taxus cuspidata, cell line
      FCL1F, and in developing callus cultures of T. cuspidata. All compounds tested
      were included in media at stationary phase (suspensions) or after the period of
      fastest growth (calli). Alanine and 3-amino-3-phenyl-propionicacid were tested
      only in callus cultures and did not affect taxol accumulation. Significant
      increases or trends toward increases in taxol accumulationin callus and
      suspensions were observed in the presence of phenylalanine, benzoic acid, N
      benzoylglycine, serine, and glycine. The greatest increases in taxol accumulation
      were observed in the presence of various concentrations of phenylalanine (1 mM
      for callus; 0.05, 0.1, and 0.2 mM for suspensions) and benzoic acid (0.2 and 1 mM
      for callus and 0.05, 0.1, and 0.2 mM for suspensions). Increases in taxol yields
      of cell suspensions in the presence of the most effective precursors brought
      taxol amounts at stationary phase from 2 mug . g(-1) to approximately 10 mug . g(
      1) of the extracted dry weight. The results are discussed in termsof possible
      implications to taxol biosynthesis and in terms of practical applications to
      large-scale cell culture systems for the production ofthis drug. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618916
TI  - Effects of intermolecular thiol-disulfide interchange reactions on bsa fouling
      during microfiltration.
AB  - Several studies have shown that one of the critical factors governing protein
      fouling of microfiltration membranes is the presence of denaturedand/or
      aggregated protein in the bulk solutions. Experiments were performed to evaluate
      the role of intermolecular disulfide interchange reactionson protein aggregation
      and membrane fouling during stirred cell microfiltration of bovine serum albumin
      (BSA). The flux decline during BSA filtration was quite dramatic due to the
      formation of a protein deposit thatfully covered the membrane pores. This flux
      decline could be completely eliminated by capping the free sulfhydryl group
      present on the BSA with eithera carboxymethyl or cysteinyl group, demonstrating
      the critical importance of this free thiol in the intermolecular aggregation
      reactions and, in turn, protein fouling. BSA aggregation during storage could be
      reduced by the addition of metal chelators (EDTA and citrate) or dithiothreitol,
      orby storage at lower pH (7.0) these solutions all had a significantly lower rate
      of fouling upon subsequent filtration. This behavior is completely consistent
      with the known chemistry of the thiol-disulfide interchange reaction,
      demonstrating that an understanding of these intermolecular (aggregation)
      reactions can provide a rational framework for the analysis and control of
      protein fouling in these membrane systems. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618917
TI  - Continuous, real-time monitoring of the oxygen uptake rate (OUR) in animal cell
      bioreactors.
AB  - A new method for real-time monitoring of the oxygen uptake rate (OUR) in
      bioreactors, based on dissolved oxygen (DO) measurement at two points, has been
      developed and tested extensively. The method has several distinct advantages over
      known techniques.It enables the continuous and undisturbed monitoring of OUR,
      which is conventionally impossible without gas analyzers. The technique does not
      require knowledge of k(L)a. It provides smooth, robust, and reliable signal. The
      monitoring scheme is applicable to both microbial and mammalian cell bioprocesses
      of laboratory or industrial scale. The method was successfully used in the
      cultivation of NSO-derived murine myeloma cell line producing monoclonal
      antibody. It was found that while the OUR increased with the cell density, the
      specific OUR decreased to approximately one-half at cell concentrations of 16 x
      10(6) cells/mL, indicating gradual reduction of cell respiration activity. Apart
      from the laboratory scale cultivation, the method was applied to industrial scale
      perfusion culture, as well as to processes using other cell lines. (c) 1994 John
      Wiley & Sons, Inc.

PMID- 18618918
TI  - Hyperosmotic hbridoma cell cultures: Increased monoclonal antibody production
      with addition of glycine betaine.
AB  - When mouse hybridoma cells were grown in culture media which were made
      hyperosmotic through the addition of NaCl or sucrose, the specific rate of
      antibody production increased with medium osmolality, reaching approx. 1.9 times
      the level obtained at physiological osmolality. However, due to a simultaneous
      reduction of the maximal cell density in the hyperosmotic media, the effect of
      the increased production rate did not give significant increases in the maximum
      antibody titer obtained in the cultures. When the osmoprotective compound,
      glycine betaine, was included in the NaCl- or sucrose-stressed cultures, the
      specific antibody production rate wasincreased up to 2.6-fold and maximum
      antibody titer up to twofold over that obtained in the control culture
      (physiological osmolality). A similar pattern of response was observed when other
      osmoprotective compounds (sarcosine, proline, glycine) were added to NaCl
      stressed hybridoma cell cultures. For the present experiments, the results
      suggest that medium osmolality, rather than growth rate, will determine the
      specific antibody production rate by hybridoma cell line 6H11 growing in
      hyperosmotic culture media. (c) 1994 John Wiley & Sons, Inc.

PMID- 18618919
TI  - Biosorption of mercury by the inactivated cells of pseudomonas aeruginosa PU21
      (Rip64).
AB  - Biomass of a mercury-resistant strain Pseudomonas aeruginosa PU21 (Rip64) and
      hydrogen-form cation exchange resin (AG 50W-X8) were investigated for their
      ability to adsorb mercury. The maximum adsorption capacity was approximately 180
      mg Hg/g dry cell in deionized water and 400 mg Hg/g dry cell in sodium phosphate
      solution at pH 7.4, higher than the maximum mercury uptake capacity in the cation
      exchange resin (100 mg Hg/g dry resin in deionized water). The mercury
      selectivity of the biomass over sodium ions was evaluated when 50 mM and 150 mM
      of Na(+) were present. Biosorption of mercury was also examined in sodium
      phosphate solution andphosphate-buffered saline solution (pH 7.0), containing
      50mM and 150 mM of Na(+), respectively. It was found that the presence of Na(+)
      did not severely affect the biosorption of Hg(2+), indicating a high mercury
      selectivity ofthe biomass over sodium ions. In contrast, the mercury uptake by
      the ion exchange resin was strongly inhibited by high sodium concentrations. The
      mercury biosorption was most favorable in sodium phosphate solution (pH 7.4),
      with a more than twofold increase in the maximum mercury uptake capacity. The pH
      was found to affect the adsorption of Hg(2+)bythe biomass and the optimal pH
      value was approximately 7.4. The adsorption of mercury on the biomass and the ion
      exchange resin appeared to follow theLangmuir or Freundlich adsorption isotherms.
      (c) 1994 John Wiley & Sons, Inc.

PMID- 18618920
TI  - The influence of dissolved oxygen tension on the synthesis of the antibiotic
      difficidin by bacillus subtilis.
AB  - The antibiotic, difficidin, and its hydroxylated derivative oxydifficidin, were
      synthesized by cultures of Bacillus subtilis grown on a complex medium. Maximum
      titers of about 200 and 130 mg/L, respectively, were obtained. In fermentations
      where the dissolved oxygen tension (DOT) was controlled, the maximum specific
      growth rate was only reduced below 5% air saturation. DOT had little effect on
      the volumetric rateof synthesis of oxydifficidin but greatly influenced the rate
      for difficidin, which was reduced at DOT values below 40% air saturation. (c)
      1994 John Wiley & Sons, Inc.

PMID- 18618921
TI  - Characterization of mixing in stirred tank bioreactors equipped with rushton
      turbines.

PMID- 18618922
TI  - Transparent chitosan derivatives for the immobilization of glutamate
      dehydrogenase.

PMID- 18618923
TI  - Assessment of the value of detecting specific IgA antibodies for the diagnosis of
      a recently acquired primary Toxoplasma infection.
AB  - OBJECTIVE: To assess the value of detecting IgA antibodies for the diagnosis of a
      recently acquired primary Toxoplasma infection. METHODS: IgA antibodies were
      screened in sera from 87 women with different serological profiles of Toxoplasma
      gondii IgM and IgG antibodies and Toxoplasma-specific IgG avidity. The IgM and
      IgG antibodies and the IgG avidity were measured with an automated Vitek Immuno
      Diagnostic Assay System (VIDAS). Anti-T.gondii IgA was measured with Platelia
      Toxo IgA TMB kits. RESULTS: All 12 sera obtained from women with clinical and/or
      serological evidence of a recently acquired Toxoplasma infection were positive
      for IgA. In 42 serum samples obtained more than 6 months after T. gondii
      infection from women with no clinical evidence of infection, but who had a
      positive IgM test and a high IgG avidity index, the IgA-enzyme linked
      immunosorbent assay (ELISA) test results were positive, negative, and doubtful in
      16 (38.1%), 23 (54.8%), and 3 (7.1%) sera, respectively. In eight women, IgA was
      detected in sera collected more than 9 months after the onset of infection. The
      IgA test result was also positive in 11 of 12 sera (91.7%) obtained from women
      with no clinical evidence of toxoplasmosis, but who had a positive IgM test and a
      borderline IgG avidity index. The IgA-ELISA was negative in 21 sera obtained more
      than 2 years after the onset of T. gondii infection from women with no clinical
      evidence of toxoplasmosis, but who had a negative IgM test and a positive IgG
      test. CONCLUSION: These results show that IgA is not a dependable marker for a
      recently acquired primary Toxoplasma infection.

PMID- 18618924
TI  - Determination of diazepam and its metabolites in human urine by liquid
      chromatography/tandem mass spectrometry using a hydrophilic polymer column.
AB  - Diazepam and its major metabolites, nordazepam, temazepam and oxazepam, in human
      urine samples, were analyzed by liquid chromatography (LC)/tandem mass
      spectrometry (MS/MS) using a hydrophilic polymer column (MSpak GF-310 4B), which
      enables direct injection of crude biological samples. Matrix compounds in urine
      were eluted first from the column, while the target compounds were retained on
      the polymer stationary phase. The analytes retained on the column were then
      eluted into an acetonitrile-rich mobile phase using a gradient separation
      technique. All compounds showed base-peak ions due to [M+H]+ ions on LC/MS with
      positive ion electrospray ionization, and product ions were produced from each
      [M+H]+ ion by LC/MS/MS. Quantification was performed by selected reaction
      monitoring. All compounds spiked into urine showed method recoveries of 50.1
      82.0%. The regression equations for all compounds showed excellent linearity in
      the range of 0.5-500 ng/mL of urine. The limits of detection and quantification
      for each compound were 0.1 and 0.5 ng/mL of urine, respectively. The intra- and
      inter-day coefficients of variation for all compounds in urine were not greater
      than 9.6%. The data obtained from actual determination of diazepam and its three
      metabolites, oxazepam, nordazepam and temazepam, in human urine after oral
      administration of diazepam, are also presented.

PMID- 18618926
TI  - Strategies for risk communication. Evolution, evidence, experience. Proceedings
      of a symposium sponsored by the Society for Risk Analysis and the National
      Science Foundation. May 15-17, 2006. Montauk, New York, USA.

PMID- 18618927
TI  - Proceedings of the Eighteenth International Conference on Genome Informatics.
      December 3-5, 2007. Biopolis, Singapore.

PMID- 18618928
TI  - Proceedings of the 10th International Congress of Therapeutic Drug Monitoring and
      Clinical Toxicology. September 9-14, 2007. Nice, France.

PMID- 18618929
TI  - Additional information on dental chew treats.

PMID- 18618930
TI  - Veterinarian speaks out against practices in horse racing.

PMID- 18618931
TI  - More insight on insurance and the veterinary profession.

PMID- 18618932
TI  - Environmental toxicology in North Rhine-Westphalia, Germany - interdisciplinary
      research activities in toxicology, statistics, hygiene and medicine. Proceedings
      of a symposium (part A). May 2007. Dortmund, Germany.

PMID- 18618933
TI  - Factors influencing the evolving practice of obstetricians in eastern Wisconsin:
      a survey.
AB  - The purpose of this survey was to ascertain what prompts clinicians in eastern
      Wisconsin to change their obstetric practice. A survey was mailed to all
      clinicians doing obstetrics for a nonprofit organization that performs over
      11,000 deliveries in 10 hospitals. Of the 185 surveys mailed, 90 (49%) practicing
      obstetricians returned it. To change their practice, 31% of respondents said they
      need the American College of Obstetricians and Gynecologists (ACOG) to recommend
      it; 24% required multiple randomized clinical trials (RCTs) from different
      centers; 11% thought one RCT was sufficient. Whereas 93% of the respondents will
      change their practice within 2 years of a new ACOG recommendation, only 67% will
      do so after an RCT (odds ratio 6.42; 95% confidence intervals 2.46, 16.75). We
      concluded that ACOG recommendations are more likely to change the practice of
      clinicians doing obstetrics in eastern Wisconsin than RCTs.

PMID- 18618934
TI  - Avian Influenza: from basic biology to pandemic planning. Proceedings of the 4th
      Educational Seminar of the Asia-Pacific Society of Respirology (ESAP). November
      30, 2007. Gold Coast, Australia.

PMID- 18618935
TI  - Proceedings of the 4th International Workshop on Neonatology/1st Meeting of
      Neonatal Infectivology. October 25-27, 2007. Cagliari, Italy.

PMID- 18618936
TI  - Proceedings of the Xth International Symposium on Insulin Receptors and Insulin
      Action. May 2-6, 2007. Stockholm, Sweden.

PMID- 18618937
TI  - Micro- and nanotechnology in electrochemical detection science. Festschrift to
      honor Professor Joseph Wang's 60th birthday.

PMID- 18618938
TI  - Diagnosis of gastric intestinal metaplasia with confocal laser endomicroscopy in
      vivo: a prospective study.
AB  - BACKGROUND AND STUDY AIMS: Gastric intestinal metaplasia (GIM) is a risk factor
      for development of intestinal-type gastric cancer. We aimed to assess the
      usefulness of confocal laser endomicroscopy (CLE) in diagnosing GIM. PATIENTS AND
      METHODS: 28 patients with known GIM underwent CLE, and CLE criteria for diagnosis
      of GIM were developed. In addition, 53 consecutive patients with known or
      suspected GIM were prospectively evaluated. RESULTS: GIM was identified if any of
      the following three features were present in an image field: goblet cells,
      columnar absorptive cells and brush border, and villiform foveolar epithelium.
      GIM was then classified as complete or incomplete according to the shape of the
      goblet cells, the presence of absorptive cells or brush border, and the
      architecture of vessels and crypts. In a prospective study, a total of 13 670 CLE
      images were obtained. Among 267 sites from 53 patients, 160 from 36 patients were
      diagnosed histopathologically as GIM. The sensitivities of conventional endoscopy
      and CLE for GIM were 36.88 % vs. 98.13 %, and the specificities were 91.59 % vs.
      95.33 %, respectively. The kappa value for the correlation with histological
      findings was 0.25 for conventional endoscopy vs. 0.94 for CLE. The sensitivity
      and specificity of CLE were 68.03 % and 89.66 %, respectively, for the diagnosis
      of complete GIM, and 68.42 % and 83.41 %, respectively, for incomplete GIM; the
      kappa value for the correspondence between CLE and histological findings was
      0.67. CONCLUSION: CLE is a useful and potentially important method for the
      diagnosis and classification of GIM in vivo.

PMID- 18618941
TI  - Introducing phase transitions to quantum chemistry: from Trouton's rule to first
      principles vaporization entropies.
AB  - In the present study, we employ quantum cluster equilibrium calculations on a
      small water cluster set in order to derive thermochemical equilibrium properties
      of the liquid phase as well as the liquid-vapor phase transition. The focus is
      set on the calculation of liquid phase entropies, from which entropies of
      vaporization at the normal boiling point of water are derived. Different
      electronic structure methods are compared and the influences of basis set size
      and of cooperative effects are discussed. In line with a previous study on the
      subject [B. Kirchner, J. Chem. Phys. 123, 204116 (2005)], we find that the
      neglect of cooperativity leads to large errors in the equilibrium cluster
      populations as well as in the obtained entropy values. In contrast, a correct
      treatment of the intermolecular many-body interaction yields liquid phase
      entropies and phase transition entropies being in very good agreement with the
      experimental reference, thus demonstrating that the quantum cluster equilibrium
      partition function intrinsically accounts for the shortcomings of the ideal gas
      partition function often employed in first principles entropy calculations.
      Comparing the calculated vaporization entropies to the value predicted by
      Trouton's rule, it is observed that for entropy calculations the consideration of
      intracluster cooperative effects is more important than the explicit treatment of
      the intercluster association even in a highly associated liquid such as water.
      The decomposition of entropy into contributions due to different degrees of
      freedom implies the need for the accurate treatment of particle
      indistinguishability and free volume of translation, whereas minor influences
      should be expected from the vibrational and rotational degrees of freedom and
      none from the electronic degrees of freedom.

PMID- 18618942
TI  - Guest editorial: fully 3-D reconstruction of medical images.

PMID- 18618940
TI  - Synaptic vesicle fusion.
AB  - The core of the neurotransmitter release machinery is formed by SNARE complexes,
      which bring the vesicle and plasma membranes together and are key for fusion, and
      by Munc18-1, which controls SNARE-complex formation and may also have a direct
      role in fusion. In addition, SNARE complex assembly is likely orchestrated by
      Munc13s and RIMs, active-zone proteins that function in vesicle priming and
      diverse forms of presynaptic plasticity. Synaptotagmin-1 mediates triggering of
      release by Ca2+, probably through interactions with SNAREs and both membranes, as
      well as through a tight interplay with complexins. Elucidation of the release
      mechanism will require a full understanding of the network of interactions among
      all these proteins and the membranes.

PMID- 18618939
TI  - Membrane fusion.
AB  - Subcellular compartmentalization, cell growth, hormone secretion and
      neurotransmission require rapid, targeted, and regulated membrane fusion. Fusion
      entails extensive lipid rearrangements by two apposed (docked) membrane vesicles,
      joining their membrane proteins and lipids and mixing their luminal contents
      without lysis. Fusion of membranes in the secretory pathway involves Rab GTPases;
      their bound 'effector' proteins, which mediate downstream steps; SNARE proteins,
      which can 'snare' each other, in cis (bound to one membrane) or in trans
      (anchored to apposed membranes); and SNARE-associated proteins (SM proteins; NSF
      or Sec18p; SNAP or Sec17p; and others) cooperating with specific lipids to
      catalyze fusion. In contrast, mitochondrial and cell-cell fusion events are
      regulated by and use distinct catalysts.

PMID- 18618943
TI  - An isoenergetic high-protein, moderate-fat diet does not compromise strength and
      fatigue during resistance exercise in women.
AB  - Resistance exercise is recommended to individuals following high-protein diets in
      order to augment changes in body composition. However, alterations in
      macronutrient composition may compromise physical performance. The present study
      investigated the effects of an isoenergetic high-protein diet on upper and lower
      limb strength and fatigue during high-intensity resistance exercise. Ten
      recreationally active women, aged 25-40 years, followed a control diet (55, 15
      and 30 % of energy from carbohydrate, protein and fat, respectively) and a high
      protein diet (respective values, 30, 40 and 30) for 7 d each in a random
      counterbalanced design. Each participant underwent strength testing of upper limb
      (isometric handgrip strength and endurance) and lower limb (four sets of sixteen
      maximal knee flexions and extensions on an isokinetic dynamometer) before and
      after applying each diet. Body weight, body fat and RER were significantly
      reduced following the high-protein diet (P < 0.05). No differences were found
      between diets in any of the strength performance parameters (handgrip strength,
      handgrip endurance, peak torque, total work and fatigue) or the responses of
      heart rate, systolic and diastolic arterial pressure, blood lactate and blood
      glucose to exercise. Women on a short-term isoenergetic high-protein, moderate
      fat diet maintained muscular strength and endurance of upper and lower limbs
      during high-intensity resistance exercise without experiencing fatigue earlier
      compared with a control diet.

PMID- 18618944
TI  - Quality of life and satisfaction with outcome among prostate-cancer survivors.

PMID- 18618945
TI  - Quality of life and satisfaction with outcome among prostate-cancer survivors.

PMID- 18618946
TI  - High-resolution analysis of genomic profiles of hepatocellular carcinoma cells
      with differential osteopontin expression.

PMID- 18618947
TI  - Coronary calcium and events in four ethnic groups.

PMID- 18618948
TI  - Coronary calcium and events in four ethnic groups.

PMID- 18618949
TI  - Coronary calcium and events in four ethnic groups.

PMID- 18618950
TI  - Coronary calcium and events in four ethnic groups.

PMID- 18618952
TI  - Case 11-2008: Mental-status changes after liver transplantation.

PMID- 18618951
TI  - VEGF inhibition and renal thrombotic microangiopathy.

PMID- 18618954
TI  - Bibliography. Current world literature. The surgical patient.

PMID- 18618953
TI  - Shifts in health information.

PMID- 18618955
TI  - Phase effects on synchronization by dynamical relaying in delay-coupled systems.
AB  - Synchronization in an array of mutually coupled systems with a finite time delay
      in coupling is studied using the Josephson junction as a model system. The sum of
      the transverse Lyapunov exponents is evaluated as a function of the parameters by
      linearizing the equation about the synchronization manifold. The dependence of
      synchronization on damping parameter, coupling constant,and time delay is studied
      numerically. The change in the dynamics of the system due to time delay and phase
      difference between the applied fields is studied. The case where a small
      frequency detuning between the applied fields is also discussed.

PMID- 18618956
TI  - Quantitative analysis of sit to stand movement: experimental set-up definition
      and application to healthy and hemiplegic adults.
AB  - Rising from a chair or sit to stand (STS) is a movement with a great clinical
      interest: it is meaningful in order to evaluate motor control and stability in
      patients with functional limitations. STS requires some skills, as coordination
      between trunk and lower limbs movements, correction of muscles strength, control
      of equilibrium and stability and it is often considered into clinical evaluation
      scales of different pathologies. In literature, although some studies are focused
      on STS, the essential functions of standing up are not well standardized and
      uniformly defined: for this reason its application in clinical centres is
      difficult. In this study an experimental set-up for acquisition of STS movement
      which is suitable for clinical applications has been proposed: first, it was
      studied in healthy subjects, to define a normative database of this specific
      motor task, then in pathological subjects (adults with hemiplegia), to quantify
      their functional limitation, using quantitative kinematic and kinetic parameters.
      The results showed that this experimental set-up is effective both in healthy and
      in pathological subjects; some significant parameters were identified and
      calculated in order to characterise and quantify the functional limitation of
      patients.

PMID- 18618957
TI  - Install ventilation systems to clear air.

PMID- 18618958
TI  - Euthanasia discussion.

PMID- 18618959
TI  - Better pay for aged care nurses.

PMID- 18618960
TI  - [Metformin in the clinical practice. Polish Society of Endocrinology consensus
      based on the European and American medical societies].

PMID- 18618961
TI  - Brief essays from the readership.

PMID- 18618962
TI  - Eye catching.

PMID- 18618963
TI  - The little agency that could (act with indifference to constitutional and
      statutory strictures).

PMID- 18618964
TI  - Dirty dancing--the FDA stumbles with the Chevron two-step: a response to
      professor Noah.

PMID- 18618965
TI  - Losing deference in the FDA's second century: judicial review, politics, and a
      diminished legacy of expertise.

PMID- 18618966
TI  - Soda battles.

PMID- 18618968
TI  - Televisuals.

PMID- 18618967
TI  - The FDA and deference lost: a self-inflicted wound or the product of a wounded
      agency? A response to Professor O'Reilly.

PMID- 18618969
TI  - FDA regulatory compliance reconsidered.

PMID- 18618970
TI  - Greater and lesser powers of tort reform: the primary jurisdiction doctrine and
      state-law claims concerning FDA-approved products.

PMID- 18618971
TI  - Drug review "behind the curtain": a response to Professor Struve.

PMID- 18618972
TI  - Food, drugs, and droods: a historical consideration of definitions and categories
      in American food and drug law.
AB  - This Article explores the evolution and interaction of the legal and cultural
      categories "food" and "drug" from the late nineteenth century to the present. The
      federal statutory definitions of "food" and "drug" have always been ambiguous and
      plastic, providing the FDA with significant regulatory flexibility. Nevertheless,
      the agency is not necessarily free to interpret the definitions however it
      chooses. "Food" and "drug" are not only product classes defined by food and drug
      law, but also fundamental cultural concepts. This Article demonstrates that the
      FDA, as well as Congress and the courts, have operated within a constraining
      cultural matrix that has limited their freedom to impose their preferred
      understandings of these categories on American society. Nonetheless, history also
      provides ample evidence that lawmakers possess substantial power to mold the
      legal categories of "food" and "drug" so as to advance desired policies. One
      explanation for this regulatory flexibility in the face of deep-seated cultural
      conceptions is the indeterminate nature of the extralegal notions of "food" and
      "drug." The terms, as commonly understood, embrace nebulous, overlapping, and
      constantly evolving realms. Moreover, the relationship between culture and law is
      not a one-way street with respect to these categories. Although the regulatory
      apparatus has always had to take into account the extralegal understandings of
      "food" and "drug," the law in turn has exerted significant influence over their
      meaning in broader culture.

PMID- 18618973
TI  - Secular Turkey's evolution battle.

PMID- 18618975
TI  - Flower show.

PMID- 18618974
TI  - Hans Meinhardt.

PMID- 18618976
TI  - Candidate biomarkers for the detection of coronary plaque destabilization and
      rupture.
AB  - Identification of high-risk patients presenting with chest pain remains
      challenging. The use of a single biomarker or a panel of biomarkers to detect
      occult plaque destabilization or rupture without frank infarction would allow for
      appropriate triage of such patients. Current data suggest that plaque
      vulnerability is determined by the relationship between forces that increase the
      size of the lipid core and destabilize the overlying thin fibrous cap. A variety
      of interrelated pathways are imputed to play important roles in this process of
      plaque evolution, destabilization, and rupture. These mechanisms include
      increased systemic and local inflammation, increased oxidative stress, matrix
      metalloproteinase modulation, and hemodynamic variables related to altered shear
      stress. Select candidate biomarkers that either reflect or influence these
      underlying processes and may ultimately have clinical application are highlighted
      in this review, which focuses on emerging biomarkers to define and predict the
      risks associated with the complex nature of vulnerable plaque biology.

PMID- 18618977
TI  - Bibliography. Current world literature. Nutrition in wasting diseases.

PMID- 18618978
TI  - Bibliography. Current world literature. Carbohydrates.

PMID- 18618979
TI  - Renewing focus and building capacity for enacting authentic collaboration in work
      rehabilitation.

PMID- 18618980
TI  - Bringing up students in the Healthy Lifestyle Multiplier Students program, Sao
      Paulo, Brazil.

PMID- 18618981
TI  - In defence of postgraduate qualifications.

PMID- 18618982
TI  - [Distraction osteogenesis: principles, history and background].
AB  - Distraction osteogenesis is a treatment in which new bone is created in the space
      which comes to exist between bone fragments that have slowly been driven apart by
      osteogenesis. This treatment, originally developed in orthopaedic surgery, is
      also commonly used for correcting deformities in the head and neck. After an
      initial hype, during which time distraction osteogenesis was used to correct
      deformities in the maxillofacial skeleton, it is beginning to become clearer for
      which conditions in the head and neck region distraction osteogenesis is most
      effective or can be seen as a good alternative for 'classical' surgical
      treatment. In this special issue, the application of distraction osteogenesis in
      orthopaedics, pre-prosthetic reconstructive surgery, orthodontics and cleft
      surgery are discussed and the mandible, the maxilla and the cranio-facial
      skeleton are also considered. In addition, the possibility that the consolidation
      period can be reduced in the case of some treatments, such as bone substitutes
      and growth factors, by combining them with distraction osteogenesis is also
      addressed.

PMID- 18618983
TI  - [Bone substitutes, growth factors and distraction osteogenesis].
AB  - Up to the present time, bone transplants are commonly used to reconstruct bone
      defects. Recently, several bone substitutes have been suggested to overcome the
      disadvantages of the procedure of bone harvesting. However, research reveals that
      an autogenous bone graft is still the gold standard. To replicate the structure
      and function of natural bone, growth factors or even living, bone-forming cells
      can be added to enhance the formation of new bone. In that case, one speaks of
      cell-based tissue-substition. As an alternative distraction osteogenesis, a
      mechanical-based way of tissue engineering is suggested. In this procedure,
      tissue-generation takes place without the addition of external material. A
      combination of both tissue-substitution techniques, consisting of the addition of
      bone-replacement materials or growth factors during distraction osteogenesis, has
      also been evaluated in research on animals, although not with unequivocal
      results.

PMID- 18618984
TI  - [Distraction osteogenesis in orthopaedics].
AB  - For several decades, distraction osteogenesis has been applied in orthopaedics
      for lengthening limbs. Other indications for distraction osteogenesis in
      orthopaedics are nonunions, open fractures, oncologic defects, and ankle
      osteoarthritis. The main principle of distraction osteogenesis is that, with a
      certain degree of distraction of 2 bone segments, linear bone generation will
      take place between the 2 segments. The most frequent complications are infection,
      loosening and breaking of the introduced pins, osteomyelitis, and fracture of the
      newly generated bone. Disadvantages of distraction appliances are expensiveness,
      degree of technical difficulty, and a long training period. Distraction
      osteogenesis in orthopaedics is a very intensive treatment. Therefore, only
      patients who are motivated and well instructed and who are physically and
      mentally capable of coping with the fixtures are suitable.

PMID- 18618985
TI  - [Using distraction osteogenesis in pre-implant surgery].
AB  - Primary stability for an implant that is placed in a prostheticaly and
      aesthetically desirable position is of essential importance for a successful
      result. A limiting factor for achieving sufficient stability for an implant is
      insufficient volume of bone at the implant site. With the help of distraction
      osteogenesis, sufficient volume of bone can be generated at the desired implant
      site. Distraction osteogenesis can be adapted for reconstructing both extremely
      resorbed mandibles and local bone defects. The various distraction techniques for
      intra-oral bone defects are enossal, extra-cortical, and a combination of
      vertical and horizontal distraction.

PMID- 18618986
TI  - [Distraction osteogenesis and orofacial anomalies].
AB  - Orofacial anomalies are generally treated by a combination of orthodontics and
      oral and maxillofacial surgery. The application of distraction osteogenesis
      offers new possibilities for treatment such as mandibular widening in the
      transverse direction and lengthening of the vertical mandibular ramus. It has
      also become apparent that distraction osteogenesis is a very useful alternative
      treatment for conventional osteotomy for the lengthening of the horizontal
      mandibular ramus in case of retrognathia and for surgical midfacial advancement
      at Le Fort I, II or III level. Widening of the maxilla by means of distraction
      osteogenesis is probably the most common application. Distraction osteogenesis
      should not be seen as a replacement for conventional osteotomies, but as a
      valuable supplement. Advantages of distraction osteogenesis over conventional
      osteotomies which are often mentioned are application at a younger age, lower
      risk of nerve damage, the displacement of the jaw or parts of the jaw over a
      greater distance, better stability of the treatment result, no need for bridging
      bonegrafts, lower surgical risk and shorter surgery time. For many advantages of
      distraction osteogenesis, however, scientific evidence is still lacking.

PMID- 18618987
TI  - [Distraction osteogenesis in patients with craniofacial anomalies].
AB  - A cleft lip and palate is the most common congenital anomaly in the craniofacial
      region. There are many other congenital craniofacial anomalies. These anomalies
      may be part of a syndrome with a wide variety of expression. Some of these
      syndromes are characterized by hypoplasia of the mandible or by hypoplasia of the
      maxilla and the orbits, often in combination with premature closure of the skull
      sutures. In addition, posttraumatic and tumour resection defects are also
      classified as craniofacial anomalies. The care for patients with craniofacial
      anomalies is highly complex and, therefore, organised in multidisciplinary
      craniofacial teams. Some craniofacial anomalies treated by distraction
      osteogenesis are mandibular hypoplasia due to hemifacial microsomia or
      temporomandibular joint ankylosis, and mid facial hypoplasia due to
      craniosynostosis.

PMID- 18618988
TI  - [Behcet's disease].
AB  - Behcet's disease is a multisystem inflammatory disorder, characterized by
      recurrent oral and genital ulceration and uveitis. Additionally, skin lesions,
      vasculitis, and arthritis may occur. The disease is chronic, with exacerbations
      and remissions. Treatment of Behcet's disease is symptomatic depending on the
      symptoms and their severity. Oral ulcers are seen in 98% of patients with
      Behcet's disease. Some aspects of oral health, such as the amount of plaque and
      the presence of periodontal disease, and possibly also caries, are more prevalent
      in patients with the disease when compared to healthy persons. All oral health
      aspects will probably benefit from good oral health care. Medications which can
      be employed for treatment of the various symptoms of the disease are colchicine,
      corticosteroids, immunosuppressives, cyclosporine, pentoxyfylline,
      anticoagulants, and thalidomide.

PMID- 18618989
TI  - Prenatal diagnosis of trisomy 21: registration results from a single genetic
      center.
AB  - This is a retrospective review of all collected amniotic fluid samples, chorionic
      villus samples and other fluid-aspirations (hygroma colli fluid/urine from
      megacystis) over an 11-year period (1996-2006) in a single Genetic Center
      (University Hospital Gasthuisberg, Leuven), looking at the prenatal diagnosis of
      trisomy 21. In this study a total of 404 diagnoses of trisomy 21 were made on
      29696 samples (1.4%). The prenatal diagnosis of trisomy 21 increased over the
      years with 0.88% (21/2363) in 1996 and 1.99% (50/2512)in 2006. Also the type of
      invasive testing changed over the years with an increase of the proportion of
      trisomy 21- diagnoses by chorionic villussampling from 2001. Looking at the
      registry for perinatal activities in Flanders for the year 2006 the live birth
      incidence for trisomy 21 was 1/1782 and this is lower than the often reported
      incidence oftrisomy 21 at birth of 1/800: it is likely that the use of more
      sensitive screening methods for the prenatal detection of trisomy 21 and the
      election of termination for most affected pregnancies affects the birth incidence
      oftrisomy 21.

PMID- 18618990
TI  - Craniosynostosis and congenital tracheal anomalies in an infant with Pfeiffer
      syndrome carrying the W290C FGFR2 mutation.
AB  - Pfeiffer syndrome (OMIM 101600) is an autosomal dominant disorder characterized
      by craniosynostosis, midface hypoplasia, ocular proptosis and digital
      malformations. We report on a type II Pfeiffer female infant with
      craniosynostosis, hydrocephalus, and characteristic craniofacial and digital
      abnormalities. The patient had a history of airway difficulty. Bronchoscopy at
      age four months revealed low tracheal stenosis and fibrous cartilaginous rings.
      She underwent tracheostomy for the treatment of cyanotic episodes. Molecular
      analysis revealed a de novo missense mutation c.870 G>T (TGG>TGT) in the FGFR2
      gene that predicts a substitution of cysteine for tryptophan at the codon 290,
      (W290C). There is phenotypic heterogeneity of tracheal anomalies due to FGFR2
      mutations. A review of the literature shows that Pfeiffer patients with the
      similar tracheal abnormalities can be caused by different FGFR2 mutations and,
      likewise, the patients with the same FGFR2 mutation may manifest different kinds
      of tracheal anomalies. Tracheal anomalies may occur in Pfeiffer patients and
      cause morbidity and mortality because of airway obstruction. Recognition and
      detailed evaluation of tracheal anomalies should be included in the early
      diagnostic workup for severe Pfeiffer patients.

PMID- 18618991
TI  - Goldenhar syndrome associated with growth hormone deficiency.
AB  - Goldenhar syndrome is a rare disorder of unknown etiology. The most frequent
      findings are vertebral defects, hemifacial microsomia and ear abnormalities. We
      present an 8-year-old boy with oculo-auriculo-vertebral (Goldenhar) syndrome. He
      also had a parachute mitral valve and growth hormone deficiency. Parachute mitral
      valve is a previously unreported finding while growth hormone deficiency was
      reported just in one case in the literature.

PMID- 18618992
TI  - Apparent Lenz microphthalmia syndrome: a patient with unusual manifestations.
AB  - Lenz microphthalmia syndrome was first described by Lenz et al. in 1955 (9). The
      cardinal features of the syndrome are microphthalmia or anophthalmia,
      microcephaly, mental retardation, external ear, digital, cardiac, skeletal,
      dental and genitourinary anomalies. Here we present a case of Lenz microphthalmia
      syndrome that shows the typical characteristics and, additionally, macrophallus,
      a broad chest with widely spaced nipples, wide gap between first and second toes,
      which are unusual manifestations in Lenz Microphthalmia Syndrome.

PMID- 18618993
TI  - Tumoral calcinosis due to GALNT3 C.516-2A >T mutation in a black African family.
AB  - Familial Tumoral Calcinosis (FTC) is a rare autosomal recessive disorder of the
      phosphocalcic metabolism caused by mutations in the FGF23 or GALNT3 genes. We
      have identified a Beninese family in which two brothers present FTC caused by a
      homozygous A>T transversion at the acceptor splice site in intron 1 of GALNT3
      gene. We report on the clinical, biochemical, histopathological and molecular
      spectrum of the disorder in this family. The particularly severe phenotype, the
      amelogenesis imperfecta, and the carbapatite deposit observed in these patients,
      seem to be characteristic of our observations.

PMID- 18618995
TI  - Partial trisomy of the distal part of 10q: a report of two Egyptian cases.
AB  - Partial trisomy of the distal third of the long arm of chromosome 10 is a well
      defined but rare syndrome. Most cases result from an unbalanced translocation.
      Growth retardation, developmental delay and characteristic dysmorphic features
      are well described in the syndrome. This report includes 2 Egyptian cases with
      partial 10q trisomy involving different breakpoints. Cases were subjected to full
      clinical examination and detailed cytogenetic analysis using conventional and
      FISH studies. Results showed that the karyotype of case 1 was
      46,XX,der(7)t(7;10)(p22;q23).ish(wcp7+;wcpl0+) and the karyotype of case 2 was
      46,XX,der(7)t(7;10)(p22;q25).ish(wcp7+;wcp 10+). The chromosomal abnormalities in
      case 1 resulted from a paternal balanced translocation while case 2 resulted from
      a maternal balanced translocation involving chromosomes 10 and 7 in both cases.
      The probands' phenotypes were correlated to the breakpoints and compared to
      previously reported cases with partial trisomy 10q. Both cases had the well
      characterized phenotype of the distal trisomy of 10q in the form of mental
      retardation, microcephaly, characteristic dysmorphic facies and limb anomalies as
      trisomy in both cases involved the 10q25-->qter region. However, case 1 with
      10q23-->qter duplication showed more severe clinical manifestations than case 2
      with less extensive 10q25-->qter trisomy. These included severe failure to
      thrive, cardiac involvement and death from respiratory and heart failure. This
      study confirmed that unbalanced chromosome regions of the long arm of chromosome
      10 play an important role in developmental malformations and that a more severe
      form is associated with involvement of 10q23. It also emphasizes the importance
      of increasing public awareness regarding these chromosomal rearrangements and the
      importance of genetic counseling and prenatal diagnosis to avoid recurrences and
      associated family stress. This was clearly demonstrated in the second family in
      this study as the couple refused any follow up or further investigations due to
      religious beliefs despite their social and educational level.

PMID- 18618994
TI  - A case with bilateral radio-ulnar synostosis.
AB  - Congenital radio-ulnar synostosis may be an isolated abnormality or additional
      abnormalities may accompany it. It may also be found as a part of well-known
      syndromes. We present a case with bilateral congenital radio-ulnar synostosis,
      speech delay, dimple on shoulders, cafe au lait spot and characteristic facial
      appearance. The proband has a brother with similar clinical findings with the
      exception of congenital radio-ulnar synostosis. We discuss the possible
      relationship between our case and previously described syndromes with congenital
      radio-ulnar synostosis, and distinct phenotypic features of the presented case.

PMID- 18618996
TI  - Prevalence of beta-thalassaemia and sickle cell traits in premarital screening in
      Al-Qassim, Saudi Arabia.
AB  - To study the prevalence of beta-thalassaemia and sickle cell traits in the Al
      Qassim region, Saudi Arabia. The Ministry of Health of Saudi Arabia launched a
      countrywide programme in February 2004 to allow all Saudis planning marriage to
      screen their carrier status for beta-thalassaemia and sickle cell traits. This
      population survey of mandatory premarital screening for beta-thalassaemia and
      sickle cell heterozygotes provided an opportunity to estimate the prevalence of
      these traits in the Al-Qassim region. From February 2004 to October 2006 all
      individuals attending for premarital screening in that region were screened. For
      each subject, venous blood was taken to determine complete blood count, red cell
      indices and hemoglobin electrophoresis. Subjects were considered to have beta
      thalassaemia trait if mean corpuscular volume was <79 fl, mean corpuscular
      haemoglobin <27 pg and haemoglobin A2 level >3.5%; and sickle cell trait if
      sickle cell haemoglobin amounted to 35 to 45% and sickling test was positive.
      Totally 38,153 individuals were screened during the study period. The prevalence
      rates of beta-thalassaemia and sickle cell traits were 0.165% (63/38,153) and
      0.252% (96/38,153) respectively. Compared with results of previous studies
      carried out in this region on the same issue, the prevalence of sickle cell
      heterozygotes seems to be the same but the frequency of beta-thalassaemia
      carriers is substantially higher. Screening for carriers both of beta
      thalassaemia and sickle cell traits is important to prevent at risk marriages
      through genetic counseling.

PMID- 18618997
TI  - Complex rearrangements of chromosome 15 in two patients with mild/atypical Prader
      Willi syndrome.
AB  - Multiple mechanisms are responsible for the development of Prader Willi syndrome
      (PWS), the most common genetic cause of obesity in childhood. Molecular findings
      are usually deletions and uniparental disomy (UPD) of the 15q11-13 region.
      Rarely, structural rearrangements of the pericentromeric region of chromosome 15
      are also detected. Two cases with mild PWS phenotype and complex maternal UPD
      identified by microsatellite analysis are described: the first patient had
      uniparental iso and heterodisomy and the second displayed biallelic inheritance
      and uniparental isodisomy.

PMID- 18618998
TI  - Sleep problems in individuals with 11q terminal deletion disorder (Jacobsen
      syndrome).
AB  - Characteristics of sleep and sleep problems were investigated in 43 individuals
      with 11q terminal deletion disorder (Jacobsen syndrome). Data were collected
      using a sleep questionnaire. Ten individuals (23%) had a sleep problem. Settling
      problems, frequent night waking and early waking occurred in 2 (4%), 7 (16%) and
      2 (6%) individuals, respectively. Twenty-two individuals (54%) had a history of
      sleep problems. Twenty-five individuals (60%) showed restless sleep and 23
      individuals (54%) slept in an unusual position. Apart from frequent coughs, no
      significant relationships were found between the presence of a sleep problem and
      other variables, such as age, level of ID, breathing problems, heart defects,
      constipation, daytime activity and behavioral diagnosis, restless sleep and
      sleeping in an unusual positions.

PMID- 18618999
TI  - An additional manifestation in acrocallosal syndrome: temporal lobe hypoplasia.
AB  - Acrocallosal Syndrome is a rare genetic disorder which is characterized by
      moderate to severe mental retardation, agenesis or hypoplasia of the corpus
      callosum and polydactyly of fingers and toes. The spectrum of this syndrome is
      very variable. Prominent forehead, broad nasal bridge, short nose and mandible,
      hypertelorism, epicanthic folds, large anterior fontanelle and tapered fingers,
      omphalocele and inguinal hernia are some other common findings in this syndrome.
      Twenty percent of the patients have associated brain abnormalities such as
      cerebral atrophy, hypothalamic dysfunction, small cerebrum, micropolygyria,
      hypoplasia of pons, hypoplasia of cerebellar hemispheres, hypoplasia of medulla
      oblongata, agenesis or hypoplasia of cerebellar vermis and corpus callosum
      abnormalities. Here we present a 10-month-old female infant with clinical and
      radiological findings indicative of acrocallosal syndrome. She was noted to have
      craniofacial abnormalities suggestive of acrocallosal syndrome, optic atrophy and
      polydactyly. MRI revealed cerebral atrophy, corpus callosum agenesis, dilated
      lateral ventricules and unilateral right temporal lobe hypoplasia, the latter not
      previously reported in the spectrum of this syndrome. Based on this observation
      we conclude the importance of screening brain abnormalities and present temporal
      lobe hypoplasia as a new additional anomaly in this syndrome.

PMID- 18619000
TI  - Speech and language in Simpson-Golabi-Behmel syndrome: a case report.
AB  - Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked disorder caused by a
      mutation of the glypican-3 gene. The physical characteristics associated with
      SGBS have been documented in several papers, but information on the behavioral
      phenotype is scarce. We report on the speech and language characteristics in an 8
      year-old-boy with SGBS. The boy performed very well on formal language tests but
      he also demonstrated poor pragmatic skills. Speech was characterized by a
      distorted articulation, distorted resonance, fluency failures, and a stereotype
      prosody. Many more case descriptions are necessary to delineate the full range of
      the behavioral phenotype of SGBS.

PMID- 18619001
TI  - Homozygosity of Hb G-Coushatta combined with heterozygous IVS-I-110(G>A) in an
      adult patient.

PMID- 18619002
TI  - Transient abnormal myelopoiesis of mosaic trisomy 21 presenting fetoplacental
      cytogenetic discrepancy, hepatosplenomegaly, oligohydramnios and abnormal
      hematological findings.

PMID- 18619003
TI  - [The internship supervisors should be scientifically competent].

PMID- 18619004
TI  - [Still misleading about fat].

PMID- 18619005
TI  - [Brain concussion can cause prolonged problems. Identification of risk patients
      as important as the emergency treatment].

PMID- 18619006
TI  - [Prehospital management of patients with severe head injuries. Scandinavian
      guidelines according to Brain Trauma Foundation].

PMID- 18619007
TI  - [S100B for diagnosis and prognosis of sequelae following minor head injury.
      Contradictory results according to studies].

PMID- 18619008
TI  - [Management of minor head injuries with the help of a blood test. S100B analysis
      can reduce the number of CT examinations and patient admissions].

PMID- 18619009
TI  - [Serial transverse enteroplasty (STEP). A new surgical technique for treatment of
      short bowel syndrome].

PMID- 18619010
TI  - [New medical requirements for driver's licence since May 1].

PMID- 18619011
TI  - [Difficult to decide when an eye disease is a disability. Patient's assessment of
      the visual function a good support for the physician's assessment].

PMID- 18619012
TI  - [Green tea can reduce the effect of Waran].

PMID- 18619013
TI  - [Who is responsible for dietary advice for our children?].

PMID- 18619014
TI  - [High-fat diet intake can be questioned].

PMID- 18619015
TI  - [Treatment outcome as quality indicator more important than accessibility].

PMID- 18619016
TI  - [Health care must never become an uncritical marketplace].

PMID- 18619018
TI  - [Drug clinical trials--the example with antidepressants].

PMID- 18619017
TI  - [The pacemaker--one of the great medical progresses--50-year anniversary].

PMID- 18619019
TI  - [Win an Oscar--live longer. Psychosocial conditions affect mortality, morbidity
      and health].

PMID- 18619020
TI  - [Adverse events in hospitals are common. The majority can be avoided according to
      a study of medical records].

PMID- 18619021
TI  - [English guidelines--nothing for children with urinary infections in Sweden].

PMID- 18619022
TI  - [Children with urinary tract infections. New scientific findings must change
      running routines].

PMID- 18619023
TI  - [Side costs--a side issue for health services? Transportation service costs and
      hemodialysis].

PMID- 18619024
TI  - [Genes and individual behavioral variations. The genome as a memory for
      experiences of the individual and the family].

PMID- 18619025
TI  - [How is it possible to live without albumin? Several cases of analbuminemia raise
      physiopathological questions].

PMID- 18619026
TI  - [Have physicians lost their ability to think?].

PMID- 18619027
TI  - [Bleeding time for preoperative screening in patients having orthognathic
      surgery].

PMID- 18619028
TI  - [HSAN, please, use the retrospectoscope with sense!].

PMID- 18619029
TI  - [Regarding kidney function assessment (GFR) with formulas].

PMID- 18619030
TI  - [Antibiotic prophylaxis against bacterial endocarditis: the physician cautioned
      for not warning his patient should not have been given caution].

PMID- 18619031
TI  - [The San people give us knowledge about the life the human species is created
      for].

PMID- 18619032
TI  - [Functions of protein MTS1 (S100A4) in normal and tumor cells].
AB  - To date vast evidence has been accumulated showing the role of protein MTS1 in
      the metastasis development and cell motility regulation, both in norm and upon
      pathological change of various tissues. The structure of the protein and its
      gene, as well as the regulation of the gene expression, are studied in detail.
      Significant advances have been achieved in understanding molecular mechanisms
      involving MTS1. This paper reviews the current knowledge of the issue.

PMID- 18619033
TI  - [Study of the Drosophila melanogaster trf2 gene and its protein product].
AB  - The Drosophila melanogaster TRF2 protein regulates transcription of several
      genes. The trf2 gene structure was studied. The gene proved to code for two
      protein isoforms, a known 75-kDa isoform and a newly identified 175-kDa isoform.
      The new isoform combines the known isoform sequence with an extended N end
      containing a coiled-coil motif. The long TRF2 isoform was found to act as a
      component of a multiprotein complex, including ISWI ATPase as well.

PMID- 18619034
TI  - [Search for protein-protein interaction partners of peroxiredoxin 6 with the
      yeast two-hybrid system].
AB  - Peroxiredoxins (Prx) are a family of nonselenium peroxidases that are involved in
      cell defense against oxidative stress and in redox regulation of intracellular
      signaling. Mammalian peroxiredoxin 6 (Prx6) belongs to the 1-Cys Prx subfamily.
      The protein--protein interactions of human Prx6 were studied using a yeast two
      hybrid system. Hybrid plasmid pHybLex/Zeo/Prx6, which directed synthesis of a
      chimeric protein consisting of the DNA-binding domain (BD) of LexA and a Prx6
      sequence, was used to screen a two-hybrid cDNA library Hybrid Hunter
      (Invitrogen). The screening identified two potential interaction partners of
      Prx6: the calcium-activated cysteine endopeptidase calpain and the p50RhoGAP
      protein of the family of Sec14-like proteins. The possibility for the
      interactions observed in the two-hybrid system to occur in oxidative stress in
      vivo is discussed.

PMID- 18619035
TI  - [Overexpression of gene PPZ1 in the yeast Saccharomyces cerevisiae affects the
      efficiency of nonsense suppression].
AB  - The phenomenon of nonsense suppression, which leads to the reading of stop codons
      as sense codons, may be related to disturbances in the operation of various
      components of the translation apparatus and the proteins interacting with them.
      The phosphatase Ppzlp is one of the factors affecting the nonsense suppression
      efficiency in the saccharomycete yeast. In this work, the impact of the
      overexpression of gene PPZ1 and its mutant allele PPZ1-R451L on the phenotypic
      expression of various mutant alleles of genes SUP35 and SUP45 or the yeast prion
      [PSI+] was analyzed. On the basis of the data obtained, a suggestion about the
      possible role of proteins Sup35p and Sup45p in the processes mediating the
      influence of gene PPZ1 overexpression on the efficiency of nonsense suppression
      is made.

PMID- 18619036
TI  - [Study of the diversity in a group of phages of Pseudomonas aeruginosa species
      PB1 (Myoviridae) and their behavior in adsorbtion-resistant bacterial mutants].
AB  - A group of 12 Pseudomonas aeruginosa virulent bacteriophages of different origin
      scored with regard to the plaque phenotype are assigned to PB1-like species based
      on the similarity in respect to morphology of particles and high DNA homology.
      Phages differ in restriction profile and the set of capsid major proteins. For
      the purpose of studying adsorption properties of these phages, 20 random
      spontaneous mutants of P. aeruginosa PAO1 with the disturbed adsorption placed in
      two groups were isolated. Mutants of the first group completely lost the ability
      to adsorb all phages of this species. It is assumed that their adsorption
      receptors are functionally inactive or lost at all, because the attempt to
      isolate phage mutants or detect natural phages of PB1 species capable of
      overcoming resistance of these bacteria failed. The second group includes five
      bacterial mutants resistant to the majority of phages belonging to species PB1,
      These mutants maintain the vigorous growth of phage SN and poor growth of phage
      9/3, which forms turbid plaques with low efficiency of plating. In the background
      of weak growth, phage 9/3 yields plaques that grew well. The examination of the
      progeny of phage 9/3, which can grow on these bacteria, showed that its DNA
      differed from DNA of the original phage 9/3 by restriction profile and is
      identical to DNA of phage PB1 with regard to this trait. Data supported a
      suggestion that this phage variant resulted from recombination of phage 9/3 DNA
      with the locus of P. aeruginosa PAO1 genome encoding the bacteriocinogenic factor
      R. However, this variant of phage 9/3 did not manifest the ability to grow on
      phage-resistant mutants of the first group. Possible reasons for the difference
      between phages 9/3 or SN and the remaining phages of PB1 species are discussed. A
      preliminary formal scheme of the modular structure for adsorption receptors on
      the surface of P. aeruginosa PAO1 bacteria was constructed based on the analysis
      of growth of some other phage species on adsorption mutants of the first type.

PMID- 18619037
TI  - [Dynamics of mitochondrial polymorphism in a natural population of Drosophila
      littoralis].
AB  - During seven years, we observed stable mtDNA polymorphism in a local population
      of Drosophila littoralis. Using RFLP, a number of mitochondrial haplotypes were
      revealed, two of which were the core and in condition of stable equilibrium. To
      explain the absence of fixation of one haplotype, we checked a hypothesis that
      the D. littoralis population had a complex structure, being subdivided into
      several partially isolated races existing on the same territory. Analysis of
      highly hypervariable nuclear sequence of retrotransposons Tv1 showed positive
      correlation of the mitochondrial haplotype with a particular allelic form of Tv1.
      This supports the proposal that the D. littoralis natural population forms the
      population system consisting of genetically differentiated races.

PMID- 18619038
TI  - [Genetic analysis of the contributions of individual chromosomes to the
      expression of mating behavior traits in Drosophila melanogaster].
AB  - The model of isogenous strains with chromosome substitutions has been used to
      estimate the relative contributions of the X chromosome and autosomes
      (chromosomes 2 and 3) to the control of some mating behavior traits in Drosophila
      melanogaster. It has been found that the male sexual activity (SA), female sexual
      receptivity (SR), and copulation latency (CL) are determined by interaction
      between X-chromosome and autosomal genes, whereas the copulation duration (CD) is
      mainly controlled by the X-chromosome genes. The synthesized isogenous strains
      have been shown to be more similar to hybrids than to the original strains. In
      the offspring with hybrid genotypes, the relationships between all traits are
      less stable, which may be related with an increase in the heterozygosity level
      and changes in genetic homeostasis.

PMID- 18619039
TI  - [New data on the distribution of hybrid necrosis genes in winter bread wheat
      (Triticum aestivum L.) cultivars].
AB  - Hybrid necrosis genotypes have been identified in 125 Russian cultivars of winter
      bread wheat. More than half of them (56%) carry the Ne2 gene (genotype
      ne1ne1Ne2Ne2); others are free of necrosis genes (genotype ne1ne1ne2ne2). The
      possible causes of the increase in the Ne2 allele frequency and the loss of the
      Ne1Ne1ne2ne2 genotype in modem Russian cultivars of winter wheat are discussed.
      The principal component method has been used to compare the structures of the
      genetic diversity of cultivars differing in the hybrid necrosis genotype. It has
      been found that the Ne2 allele in winter wheat cultivars from northern Russia has
      originated from the cultivar Mironovskaya 808, whereas the cultivar Bezostaya 1
      is not a source of this gene. In cultivars from southern Russia, the presence of
      the Ne2 allele is also mainly accounted for by the use of Mironovskaya 808 wheat
      in their breeding. The recessive genotype is explained by the presence of
      descendants of the cultivar Odesskaya 16 in the pedigrees of southern Russian
      winter wheats. The genetic relationship of cultivars with identical and different
      necrosis genotypes has been analyzed in nine regions of the Russian Federation.

PMID- 18619040
TI  - [Association of polymorphisms and haplotypes in the 5' region of COLIA1 gene with
      the risk of osteoporotic fractures in Russian women from Volga-Ural region].
AB  - The analysis of -1997G/T, -1663indelT, and +1245G/T polymorphic loci of the
      5'region of COLIA1 gene in 124 females aged from 50 to 70 years old with low
      numbers of traumatic fractures as well as 150 healthy individuals from Volga-Ural
      region has been conducted. The association of -1663indelT and +1245G/T loci with
      the risk of osteoporotic fractures has been discovered. It has been shown that 
      1997*G*G/-1663*I*D/+1245*G*T genotype combination and -1997*G/-1663*D/+1245*T
      haplotype can be considered as markers for fracture development.

PMID- 18619041
TI  - [Gene pool structure of Russian populations from the European part of Russia
      inferred from the data on Y chromosome haplogroups distribution].
AB  - Population structure of Russian population from the European part of Russia was
      investigated by analyzing the distribution of 23 SNP makers of Y chromosome in
      Russian populations from Kaluga oblast, Yaroslavl' oblast, Vladimir oblast,
      Nizhny Novgorod oblast, Pskov oblast, Tula oblast, Belgorod oblast, and Novgorod
      oblast. In the populations studied a total of 14 Y-chromosome haplogroups (E, F*,
      I, J, K*, N3a, N2, P*, R1*, R1a1, C3, H, and A) were discovered, of which
      haplogroups R1a1, I, and N3a were the prevailing. Analysis of Phi statistics in
      the populations grouped in accordance to the dialect subdivision of the Russian
      language, showed the absence of statistically significant differences between
      Russian population groups. Analysis of the Y-chromosome markers distribution
      patterns among Russian population (10 population groups) in comparison with the
      population of Germany (11 population groups) revealed statistically significant
      differences between the gene pools of Slavs (Russians and Poles) and Teutons
      (Germans).

PMID- 18619042
TI  - [Association of the chromosomal region 2q35 with type 1 diabetes mellitus in the
      Russian patients from Moscow].
AB  - To map human chromosome 2 region associated with type 1 diabetes mellitus, 89
      families with concordant and discordant sib pairs were analyzed. Linkage and
      association with type 1 diabetes were examined using polymorphic microsatellite
      markers spanning the region of about 4 Mb. The linkage plot was constructed, and
      association of the five microsatellite markers within the chromosomal region 2q35
      was examined. Polymorphic marker D2S137 (Z' = 3.225, p(c) = 0.0048) demonstrated
      maximum linkage and association with type 1 diabetes.

PMID- 18619043
TI  - [Molecular analysis of the Y chromosome in XX sex-reversed patients].
AB  - Molecular genetic analysis was performed for 26 phenotypically male patients
      lacking the Y chromosome in the karyotype. The sex-determining region Y (SRY)
      gene was found in 77% of the patients. PCR analysis of Y-specific loci in the 17
      SRY-positive patients revealed Yp fragments varying in size in 16 cases and
      cryptic mosaicism (or chimerism) for the Y chromosome in one case. The
      frequencies of class I, II, and III (Yp+)XX sex reversals were 18.75, 25.25, and
      56%, respectively. All of the class III (Yp+)XX sex-reversed patients had a 3.5
      Mb paracentric inversion flanked by inverted repeats 3 (IR3) on the short arm of
      the Y chromosome.

PMID- 18619044
TI  - [Polymorphism in promoter regions of matrix metalloproteinases (MMP1, MMP9, and
      MMP12) in chronic obstructive pulmonary disease patients].
AB  - Our studies have shown that the genotype and allele frequencies of polymorphisms
      G(-1607)GG of MMPI gene, C(-1562)T of MMP9 gene and A(-82)G of MMP12 gene do not
      significantly differ in the samples of chronic obstructive pulmonary disease
      (COPD) patients (N = 318) and healthy controls (N = 319) dwelling in
      Bashkortostan Republic. However, association of (-1562)T allele of the MMP9 gene
      with the severity of COPD disease progression has been revealed. In COPD patients
      at stage 4 of the disease, the frequency of allele T was significantly higher
      that in patients with the stages 2 and 3 (15.89% versus 8.38%; chi2 = 7.804, d.f.
      = 1, P = = 0.005; OR = 2.06 95% CI 1.22-3.49). The distribution of the genotype
      frequencies of C(-1562)T polymorphism of MMP9 gene significantly differed between
      the patients with various COPD severity (chi2 = 9.849, d.f. = 2, P = 0.007). The
      individuals with rare genotype TT were revealed only among patients with severe
      COPD form (3.97% versus 0%; chi2 = 4.78, P = 0.029, Pcor = 0.058). Analysis of
      this polymorphism in patients with early COPD onset (younger than 55 years old)
      has shown a significant increase in the allele Tfrequency in the group of
      patients with severe COPD (stage 4 according to GOLD) compared to the patients of
      the same age but with less severe COPD progression (chi2 = 5.26, d.f. = 1, P =
      0.022). As the major clinical characteristics of stage 4 COPD is the development
      of pulmonary emphysema as well as bronchial walls deformation, we suggest that
      the increased expression of MMP9 gene caused by genetic polymorphism in the gene
      promoter is important in the early development of serious complications of the
      disease.

PMID- 18619045
TI  - [Human chromosome 3P regions of putative tumor-suppressor genes in renal, breast,
      and ovarian carcinomas].
AB  - Allelic imbalances (AI) of polymorphic markers at the short arm of chromosome 3
      (3p) were mapped using DNA samples of renal cell carcinoma (RCC, 80 cases),
      breast carcinoma (BC, 95 cases), and epithelial ovarian cancer (EOC, 50 cases) at
      the same dense panel of markers (up to 24 loci). Six regions with the increased
      AI frequency (versus the average values determined for all the analyzed 3p
      markers) at RCC, BC or EOC were found in 3p chromosome. Four 3p regions
      presumably contain suppressor genes of tumor growth (TSG) observed in the
      epithelial tumors of various types. Region between D3S2409 and D3S3667 markers in
      the 3q21.31 region was identified in this study for the first time. The AI peak
      in D3S2409-D3S3667 region was statistically significant (P < 0.001, according to
      Fisher) when representative sample of 95 BC patients was analyzed. The data on
      increased frequency of polymorphic marker allele amplification suggest that the
      D3S2409-D3S3667 region contains both putative TSG and protooncogenes.

PMID- 18619046
TI  - [Mitochondrial DNA diversity in Siberian Tatars of the Tobol-Irtysh basin].
AB  - Data on the variation of the nucleotide sequence of hypervariable segment I
      (HVSI) and restriction fragment length polymorphism (RFLP) of the coding region
      of mitochondrial DNA (mtDNA) have been used to characterize the mitochondrial
      gene pool of Siberian Tatars of the Tobol-Irtysh basin (N = 218), one of three
      geographic/linguistic groups of Siberian Tatars. The gene pool of Siberian Tatars
      has been shown to contain both Asian and European mtDNA lineages at a ratio of 1
      : 1.5. The mtDNA diversity of Siberian Tatars is substantially higher than that
      of other Turkic-speaking populations of North and Central Asia. The position of
      the mitochondrial gene pool of Tatars of the Tobol-Irtysh basin in the genetic
      space of northern Eurasia populations has been determined.

PMID- 18619047
TI  - [Biometric-genetic analysis of genotype dissimilarity: the model and parameters].
AB  - An additive-dominant model and parameters for biometric--genetic analysis of pair
      dissimilarity between genotypes have been developed. The analyzed dissimilarity
      metrics are presumed to be determined by the quantitative traits of plant lines
      and F1 hybrids obtained by diallel crossing. Relationships between dissimilarity
      parameters have been determined, and algorithms for estimating their use, in
      particular, for detecting the most heterozygous hybrids are suggested.

PMID- 18619048
TI  - [Biometric-genetic analysis of genotype dissimilarity in diallel crosses of
      spring wheat].
AB  - A new biometric-genetic model and parameters described in [1] have been used for
      analysis of pair dissimilarity between spring wheat cultivars and F1 hybrids
      obtained by diallel crossing. The dissimilarity between the reactions of
      different genotypes estimated by a growth trait (plant height) served as a
      metric. The mode of inheritance of dissimilarity has been determined, and the
      cultivars that are the most dissimilar in allelic composition have been detected.

PMID- 18619049
TI  - [Genetic divergence of Vipera berus and Vipera nikolskii (Reptilia: Viperidae,
      Vipera) populations in lower Volga and adjacent territories assessed according to
      the sequences of cytochrome oxidase III 12S ribosome RNA genes].
AB  - The nucleotide sequences of mitochondrial genome fragments containing the genes
      coding for cytochrome oxidase subunit III (COIII) and 12S ribosomal RNA of common
      European viper and Nikolsky's viper from various habitats (Saratov, Samara, and
      Penza oblasts; Chuvash Republic; and the Republic of Mordovia) were determined.
      According to the sequencing data, all samples clustered into two groups except
      for a number of individuals carrying single mutations in the genes in question.
      One group comprised V. nikolskii from Saratov oblast and the other, V. berus from
      the Chuvash Republic, Republic of Mordovia, and Samara and Penza oblasts. These
      results comply with the available data on the karyotypes of the studied vipers of
      this region. Further genetic studies of V. nikolskii and V. berus from various
      parts of this area are necessary.

PMID- 18619050
TI  - [Microarray design using virtual hybridization to study variations in REP-CMT1A
      sites].
AB  - BACKGROUND: Gene PMP22 is duplicated in patients with CMT1A. Duplication is due
      to an unequal chromatid interchange during meiosis that takes place between two
      24 Kb regions named REP-CMT1A proximal and distal sites. Homology is
      approximately 98%. Within each one of the sites we find zones termed hot spots
      where a greater number of variants and mutations could give origin to an unequal
      interchange. The aim of this study was to design a set of probes to create a
      microarray that could detect the presence of variants and mutation points in
      distal and proximal REP sites among patients with CMT1A. MATERIAL AND METHODS:
      With reported sequences of distal and proximal REPs, we determined hot spot sites
      within proximal and distal regions. These sequences were aligned and matched,
      hence 12 zones were detected. RESULTS AND CONCLUSIONS: Twenty four probes were
      designed and analyzed using the Genosensor Probe Designer program. Probes could
      be synthesized and used in a microarray that is able to find variations and
      mutation points and facilitates diagnosis of patients with CMT1A.

PMID- 18619051
TI  - [Onychomycosis among children. A retrospective study of 233 Mexican cases].
AB  - BACKGROUND: Worldwide recent reports point towards a rising prevalence
      ofonychomycosis in the pediatric population, especially among adolescents.
      Dermatophytes are the most common etiologic agents. MATERIAL AND METHODS: We
      carried out a retrospective review of the last 12 years, comprising 332 medical
      records from children with clinical suspicion of onychomycosis. We analyzed the
      following variables: gender, age, predisposing factors, affected nails, other
      concurrent superficial mycoses and potassium hydroxide direct examination and
      culture. RESULTS: A total of 233 onychomycosis cases were identified, cases
      constituted 33% of superficial mycoses of children seen at our unit. Two thirds
      were adolescents with no significant difference among the sexes. Toenails were
      more affected (94%) than fingernails (4.2%) with distal and lateral subungueal
      onychomycosis being the most common clinical presentation. In 70% of cases
      infection was caused by dermatophytes (mainly Trichophyton rubrum). CONCLUSIONS:
      Onychomycosis constitute 33% of superficial mycoses among children seen at our
      medical facility. We confirm a rise in prevalence, toenails were the most common
      (94%) and had a dermatophytic etiology (70%). We suggest to all physicians caring
      for children and adolescents, to become familiar with diagnostic and therapeutic
      tools for this type of mycosis.

PMID- 18619052
TI  - [Levels of soluble adhesion molecules among normal and hypertensive type 2
      diabetic patients].
AB  - BACKGROUND: Hypertension and type-2 diabetes affect endothelial function, which
      in turn increases the expression of soluble adhesion molecules and lead to the
      development of vascular damage. The aim of this study was to assess soluble
      adhesion molecule levels among normotensive and hypertensive diabetic patients.
      MATERIAL AND METHODS: Serum levels of soluble VCAM1, ICAM1 and e-selectin were
      measured in 80 type-2 diabetic patients, (40 normotensive and 40 hypertensive),
      and in 40 normotensive non-diabetic subjects by ELISA (RyDSystems Minneapolis).
      Statistical analysis was performed with ANOVA. RESULTS: Among diabetic patients,
      levels of all three soluble adhesion molecules were significantly increased when
      compared with non-diabetic patients (p < 0.001 for all three molecules), In
      diabetic hypertensive patients, higher levels of ICAM1 were detected in
      comparison to normotensive diabetic patients (316 vs. 295 ng/ml p < 0.01), VCAM1
      and e-selectin levels were not different between diabetic patients with and
      without hypertension. CONCLUSIONS: Diabetes is associated with increased levels
      of soluble adhesion molecules, suggesting a role of these molecules may play in
      endothelial damage. ICAM1 is further increased when hypertension and diabetes are
      present. The latter may explain why diabetic-hypertensive patients displayed more
      complications than normotensive patients.

PMID- 18619053
TI  - [Sellar remodeling: a surgical option for primary empty sella syndrome].
AB  - BACKGROUND: The empty sella is an entity that only rarely presents signs and
      symptoms. When noted, visual field deficits are an indication for surgical
      management. MATERIAL AND METHODS: We studied twenty patients with primary empty
      sella and visual field deficits surgically treated with a technique termed by us
      as "sellar remodeling." We treated 19 females and 1 male. Aside from visual
      deficits, all participants reported headache. We reported an increase in
      prolactin serum level in three cases. Patients with an increase in cerebrospinal
      fluid pressure were excluded. The surgical procedure involved placing through a
      transsphenoidal route an autologus graft formed by fat, aponeurosis and two bone
      lamina, with precise dimensions according to each patient's sella turcica.
      RESULTS: After surgery, visual deficits improved in 18 patients and headache in
      17. Two patients displayed normal prolactin levels. No serious complications were
      reported during surgery. CONCLUSIONS: Sellar remodeling is a precise, simple,
      safe and inexpensive technique that significantly improves symptoms such as
      visual deficits and headache observed in primary empty sella syndrome.

PMID- 18619054
TI  - [Antifungal resistance: an emerging problem in Mexico].
AB  - BACKGROUND: An increase in mycosis associated with therapeutic failure has been
      observed worldwide. The dearth of data in Mexico led us to study antifungal
      resistance. MATERIAL AND METHODS: Seventy six isolates of patients from the
      Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano
      del Seguro Social were included: 36 with dermatophytoses and 40 with candidiasis.
      Dermatophytes were assesed using the E-test method and Candida spp. using the
      broth microdilution method. Antifungal drugs included itraconazole, ketoconazole
      and fluconazole for dermatophytes; in addition, voriconazole and amphotericin B
      were used to treat yeasts. RESULTS: From the 36 dermatophytes, seven isolates
      (19.4%) showed resistance to one or more antifungal drugs: three to Trichophyton
      rubrum, three to T. mentagrophytes and one to T. tonsurans. One T. rubrum isolate
      was resistant to the three azoles; the other six isolates were resistant to
      fluconazole only. From the 40 Candida isolates, 11 (27.5%) showed resistance:
      seven to ketoconazole and itraconazole; three only to itraconazole and one to
      ketoconazole. One C. glabrata isolate showed resistance to the four azoles. None
      of the yeasts showed resistance to amphotericin B. CONCLUSION: Therapeutic
      failure could be caused by drug resistance. In our study we found an antifungal
      resistance of 20% and 27.5% in dermatophytes and in yeasts respectively.

PMID- 18619055
TI  - [Recurrence and survival rates among early breast cancer cases with triple
      negative immunophenotype].
AB  - BACKGROUND: Axillary lymph node status, hormonal receptors (HR) and HER2
      expression are significant prognostic factors for early breast cancer. Triple
      negative immunophenotype (HER2 and HR negative) is associated with a high
      frequency of recurrence and lower overall survival. The objective was assess
      clinical behavior, recurrence and survival of patients with triple negative early
      breast cancer and patients with other immunophenotypes. MATERIAL AND METHODS: We
      carried out a retrospective study among women with stages I-IIB over 18 years
      with determination of HR and HER2 expression by immunohistochemical assay. We
      identified 5 groups: triple negative, triple positive, HER2 negative & HR
      positive, HER2 positive & HR negative, HER2 negative & 1 HR positive. We recorded
      age, date of diagnosis, clinical stage, tumor size, axillary lymph node status,
      ER, PR, HER2, p53, angiogenesis, Ki67, type of surgery, adjuvant treatment, time
      to recurrence, number and recurrence site and overall survival. RESULTS: 17
      patients (15.4%) had triple negative phenotype, 14 (12.7%) triple positive, 52
      (47.3%) were localized in group 3, 11 (10%) in 4 and 16 (14.5%) in group 5.
      Triple negative phenotype was associated with increased cellular proliferation (p
      < 0.000); being young (median 43 years), large tumor size (median size 2.5 cm)
      lower proportion of patients in stage I and high frequency of p53 positive
      (78.5%). We observed a high frequency of recurrence and death among the triple
      negative group and among the HER2 positive and HR negative cases. CONCLUSIONS:
      Triple negative breast cancer is more common among young women and is associated
      with a high frequency of recurrence and mortality. Clinical behavior among triple
      negative breast cancer cases is aggressive and displays a similar clinical
      profile that observed among HER2 positive and HR negative patients.

PMID- 18619056
TI  - [Ultraviolet absorption of prescription sunblocks in Mexico].
AB  - BACKGROUND: An appropriate sunscreen should provide high and broad ultraviolet
      protection both for the B and A range. The objective was quantify the ultraviolet
      absorption spectrum in sunscreens available for medical prescription, and analyze
      its relationship with the labeled Sun Protection Factor (SPF). MATERIAL AND
      METHODS: Thirty-nine sunscreens were analyzed in vitro using ultraviolet
      spectroscopy following exposure to simulated solar irradiation. RESULTS: Fifty
      six percent of sunscreens absorbed 90% or more of ultraviolet radiation. Seventy
      five percent (n = 34) absorbed more than 95% of ultraviolet B radiation, and 46%
      (n = 18) more than 90% of ultraviolet A. There was no significant association
      between ultraviolet absorption and SPF. CONCLUSION: We were unable to estimate
      ultraviolet absorption only by its SPF. Protection differed considerably among
      products with similar SPF. Our study highlights regulation deficiencies in
      marketing practices of these products.

PMID- 18619057
TI  - [Obesity, inflammation and diabetes].
AB  - Integration of metabolism and immunity in normal physiology is beneficial to
      maintain homeostasis. It can also become deleterious under conditions such as the
      immunosuppression observed among the malnourished. With the increase of excess
      weight and obesity, a new set of problems and complications has emerged at the
      intersection of metabolic activity and immunity. As examples of the latter we
      find obesity associated with inflammatory diseases, diabetes, fatty liver disease
      and atherosclerosis. Obesity is characterized by inflammation; there are common
      factors at the crossroads of inflammation and metabolic disease. Obesity is
      characterized by an inflammatory response and many inflammatory mediators exhibit
      expression patterns that interfere with insulin action. The high level of
      coordination of inflammatory and metabolic pathways is highlighted by the
      overlapping biology of macrophage and adipocite function observed in obesity. The
      intracellular signaling pathways activated by inflammatory and stress responses
      inhibit insulin signaling and the loss of inflammatory mediators prevents insulin
      resistance. In the absence of obesity, an infusion of inflammatory cytokines or
      lipids causes insulin resistance. Understanding the mechanisms leading from
      obesity to inflammation will have important implications to help reduce the
      morbidity and mortality associated with obesity by preventing its association
      with inflammatory disorders.

PMID- 18619058
TI  - [Hypophyseal incidentalomas].
AB  - The rapid development of highly accurate imaging techniques, has led to the
      discovery of asymptomatic lesions within the pituitary gland that constitute a
      significant challenge for clinicians and neurosurgeons. These lesions found
      incidentally are termed incidentalomas and can be observed in approximately 10%
      of MRI studies performed among healthy subjects. The natural course of these
      lesions has not been clearly defined. Although some of these masses do not change
      in size overtime and some may even shrink spontaneously, others have the
      potential risk to increase in volume and cause symptoms associated with mass
      effect or hormonal hypersecretion. This review describes the current therapeutic
      and diagnostic consensus in incidentaloma management, and places special emphasis
      on hormonal and imaging factors suggestive of high risk tumors.

PMID- 18619059
TI  - [A review of interferons: fifty years later (1957-2007)].
AB  - Initially identified as a defense mechanism against viral infections, in the last
      50 years interferons have been defined a group of substances belonging to the
      cytokine family indispensable for the normal functioning of the immune system.
      Derived from their pleiotropic functions interferons were the first biological
      products used to treat several diseases. Their properties have progressively
      placed them as the first treatment choice for chronic infection with hepatitis B
      virus, hepatitis C virus, multiple sclerosis, some forms of leukemia, melanoma,
      etc. It has been noted however that the administration of supra physiological
      doses of interferons with therapeutic objectives, independently of its primary
      indication, has been associated with significant toxicity, including autoimmunity
      and induction of more than thirty different autoimmune diseases.

PMID- 18619060
TI  - [Confluent and reticulated Gougerot-Carteaud papillomatosis: a case report of an
      excellent response to minocycline].
AB  - Confluent and reticulated Gougerot-Carteaud papillomatosis is an uncommon
      dermatological condition that affects adolescents, especially young women with
      dark skin types. It presents itself as asymptomatic pigmented patches with a
      papillomatous texture that coalesce to form reticular plaques localized in the
      neck and intertriginous areas. The cause of this disease is unknown, although an
      abnormal keratinization has been implicated and sometimes has been associated
      with Malassezia sp. It has a chronic course with remissions and exacerbations.
      Several therapies have been used unsuccessfully to eradicate it but nowadays
      there is no specific treatment. We report a case treated efficiently with
      minocycline without recurrence at 6 months follow-up.

PMID- 18619061
TI  - [A 74-year-old man with rhinorrhea and recurrent epistaxis].

PMID- 18619062
TI  - [A new therapeutic strategy to control HIV? The PD1 molecule and its role in
      inhibiting cellular immune responses].
AB  - CD8+ T cells are crucial in protecting against viral infections by secreting
      antiviral factors and lysing infected cells. The loss of these functions is a
      hallmark of various chronic viral infections. In HIV chronic infection, CD8+ T
      cells develop this exhausted phenotype and their protection capacities diminish.
      Recently, it has been shown that a co-inhibitory molecule called PD-1 plays an
      important role on this exhausted phenotype. These findings open up the
      possibility of research targeted to develop therapeutic interventions that may
      restore CD8+ T cell function in chronic HIV infection.

PMID- 18619063
TI  - Nurses score big during legislative session.

PMID- 18619064
TI  - Research on Bi-Bi instruction.

PMID- 18619065
TI  - Wanted: brains and hearts.

PMID- 18619066
TI  - A summary of the reading comprehension research undertaken with students who are
      deaf or hard of hearing.
AB  - The American Federation of Teachers (1999) has stated that "the most fundamental
      responsibility of schools is teaching students to read" (p. 7). The central
      purpose of reading is comprehension--constructing meaning from text. The purpose
      of the present study was to identify, review, and summarize the research
      published in professional peer-reviewed journals related to reading comprehension
      and school-age students who are deaf or hard of hearing between 1963 and 2005.
      Fifty-two studies were identified and reviewed. The results were summarized in a
      table and reported descriptively. The most frequently researched reading
      comprehension teaching strategies were identified and discussed. The need for
      more research in this critical area was noted.

PMID- 18619067
TI  - Learning English from signed English: an impossible task?
AB  - A sample of elementary school- and high school-age deaf students in special
      education programs in the Australian state of Queensland using Australasian
      Signed English (ASE) took the Test of Syntactic Abilities (Quigley, Steinkamp,
      Power, & Jones, 1978) and wrote a story in response to a wordless picture
      sequence. Several analyses of the students' test scores and of the written
      language of their stories were undertaken. It was found that classroom use of ASE
      was of benefit to these students in developing English and telling a story in
      writing, but that there were complex aspects of syntax that required special
      teaching. The implications for the use of Signed English systems and the teaching
      of English to deaf students who use Signed English communication are examined.

PMID- 18619069
TI  - Identification and placement for deaf students with multiple disabilities:
      choosing the path less followed.
AB  - Students with a hearing loss often have an additional disability. Although the
      number of deaf students with multiple disabilities is growing, research on this
      population has significantly decreased over the past quarter-century. The article
      reviews the literature on identification and placement of deaf students with
      multiple disabilities, specifically deaf students with one of the following
      disabilities: autism, emotional/behavior disorders, attention deficit disorders,
      or mental retardation. Degree of incidence is also reported, and is compared with
      statistics from the annual report of the Gallaudet Research Institute (2005).
      Included in the review are suggestions for future research and implications for
      professionals in the field of deafness.

PMID- 18619070
TI  - The linguistic milieu of Norwegian children with hearing loss.
AB  - The article is based on a national survey in Norway of the linguistic situation
      of deaf children. Parents, teachers, and children were asked to make judgments on
      topics related to the children's language milieu at home and at school by means
      of detailed questions using two response methods: a language inventory and rating
      scales. The inventory is more detailed than those in other studies and required
      all three groups to consider not only the use of the two native languages,
      Norwegian and Norwegian Sign Language, but other forms combining sign and speech.
      The data revealed that languages used with the children included both native
      languages as well as various mixtures depending on context, situation, and the
      nature and purpose of the communication. The results are considered from the
      perspective of the amount and quality of language input and intake necessary for
      language acquisition and literacy.

PMID- 18619068
TI  - Lessons learned from more than two decades of HIV/AIDS prevention efforts:
      implications for people who are deaf or hard of hearing.
AB  - In contrast with the nearly 30 years of HIV/AIDS research with the hearing
      community, data on HIV infection among persons who are deaf and hard of hearing
      is primarily anecdotal. Although the few available estimates suggest that deaf
      and hard of hearing persons are disproportionately affected by HIV infection, no
      surveillance systems are in place to identify either frequency or mode of HIV
      infection within this population. Moreover, to date, all empirically validated
      HIV prevention interventions have relied on communication strategies developed
      for persons who hear. Therefore, understanding and developing effective
      prevention methods is crucial for persons who are deaf or hard of hearing. The
      authors explore (a) factors among this population that may contribute to HIV
      related behaviors, (b) four key concepts consistently included in successful
      interventions, and (c) practical ways in which to use this information to tailor
      effective intervention strategies for this population.

PMID- 18619071
TI  - The status of sign language instruction in institutions of higher education: 1994
      2004.
AB  - Surveys of sign language programs in institutions of higher education in the
      United States, conducted in 1994 and 2004, are compared to reveal changes over
      time. Data are presented concerning the institutional environment of programs,
      program administrators, and instructors. Institutions examined in 2004 were on
      average 5 years older than those examined in 1994. More institutions accepted
      sign language for general education and foreign language requirements. Program
      administrators in 2004 were more likely to have primary duties as teachers rather
      than administrators, and to have greater understanding of the subject matter.
      Faculty in 2004 had more education and teaching experience. Full-time faculty
      showed increases in the proportion who were Deaf and the proportion who were in
      tenure-track positions. Program staff size increased. Overall, evidence indicates
      that sign language has become more accepted as an academic discipline and that
      programs are more entrenched at their institutions.

PMID- 18619072
TI  - Computer-mediated communication and the Gallaudet University community: a
      preliminary report.
AB  - The study examined the use of computer-mediated communication (CMC) among
      individuals involved in a conflict sparked by the appointment of an administrator
      as president-designate of Gallaudet University in 2006. CMC was defined as forms
      of communication used for transmitting (sharing) information through networks
      with digital devices. There were 662 survey respondents. Respondents reported
      overwhelmingly (98%) that they used CMC to communicate. Students and alumni
      reported CMC use in larger proportions than any other group. The favorite devices
      among all respondents were Sidekicks, stationary computers, and laptops. Half of
      all respondents also reported using some form of video device. Nearly all
      reported using e-mail; respondents also identified Web surfing, text messaging,
      and blogging as popular CMC activities. The authors plan another article
      reporting on computer and electronic technology use as a mechanism connecting
      collective identity to social movements.

PMID- 18619073
TI  - The family physician's role in assessing impairment and disability.

PMID- 18619074
TI  - Importance of vaccinations for close contacts and caregivers.

PMID- 18619075
TI  - What others take for granted.

PMID- 18619076
TI  - Food allergies: detection and management.
AB  - Family physicians play a central role in the suspicion and diagnosis of
      immunoglobulin E-mediated food allergies, but they are also critical in
      redirecting the evaluation for symptoms that patients are falsely attributing to
      allergies. Although any food is a potential allergen, more than 90 percent of
      acute systemic reactions to food in children are from eggs, milk, soy, wheat, or
      peanuts, and in adults are from crustaceans, tree nuts, peanuts, or fish. The
      oral allergy syndrome is more common than anaphylactic reactions to food, but
      symptoms are transient and limited to the mouth and throat. Skin-prick and
      radioallergosorbent tests for particular foods have about an 85 percent
      sensitivity and 30 to 60 percent specificity. Intradermal testing has a higher
      false-positive rate and greater risk of adverse reactions; therefore, it should
      not be used for initial evaluations. The double-blind, placebo-controlled food
      challenge remains the most specific test for confirming diagnosis. Treatment is
      through recognition and avoidance of the responsible food. Patients with
      anaphylactic reactions need emergent epinephrine and instruction in self
      administration in the event of inadvertent exposure. Antihistamines can be used
      for more minor reactions.

PMID- 18619077
TI  - Food allergies: what you should know.

PMID- 18619078
TI  - Impairment and disability evaluation: the role of the family physician.
AB  - Physicians are frequently involved in the assessment of impairment and disability
      as the treating physician, in consultation, or as an independent medical
      examiner. The key elements of this assessment include a comprehensive clinical
      evaluation and appropriate standardized testing to establish the diagnosis,
      characterize the severity of impairment, and communicate the patient's abilities,
      restrictions, and need for accommodation. In some cases, a functional capacity
      evaluation performed by a physical or occupational therapist or a
      neuropsychological evaluation performed by a neuropsychologist may be required to
      further clarify the functional capacity of the patient. The results of the
      impairment evaluation should be communicated in clear, simple terms to nonmedical
      professionals representing the benefits systems. These individuals make the final
      determination on the extent of disability and eligibility for benefits and
      compensation under that particular benefits system.

PMID- 18619079
TI  - Gastrointestinal complications of diabetes.
AB  - Gastrointestinal complications of diabetes include gastroparesis, intestinal
      enteropathy (which can cause diarrhea, constipation, and fecal incontinence), and
      nonalcoholic fatty liver disease. Patients with gastroparesis may present with
      early satiety, nausea, vomiting, bloating, postprandial fullness, or upper
      abdominal pain. The diagnosis of diabetic gastroparesis is made when other causes
      are excluded and postprandial gastric stasis is confirmed by gastric emptying
      scintigraphy. Whenever possible, patients should discontinue medications that
      exacerbate gastric dysmotility; control blood glucose levels; increase the liquid
      content of their diet; eat smaller meals more often; discontinue the use of
      tobacco products; and reduce the intake of insoluble dietary fiber, foods high in
      fat, and alcohol. Prokinetic agents (e.g., metoclopramide, erythromycin) may be
      helpful in controlling symptoms of gastroparesis. Treatment of diabetes-related
      constipation and diarrhea is aimed at supportive measures and symptom control.
      Nonalcoholic fatty liver disease is common in persons who are obese and who have
      diabetes. In persons with diabetes who have elevated hepatic transaminase levels,
      it is important to search for other causes of liver disease, including hepatitis
      and hemochromatosis. Gradual weight loss, control of blood glucose levels, and
      use of medications (e.g., pioglitazone, metformin) may normalize hepatic
      transaminase levels, but the clinical benefit of aggressively treating
      nonalcoholic fatty liver disease is unknown. Controlling blood glucose levels is
      important for managing most gastrointestinal complications.

PMID- 18619080
TI  - Gastroparesis: what you should know.

PMID- 18619081
TI  - Venous thromboembolism during pregnancy.
AB  - Venous thromboembolism is the leading cause of maternal death in the United
      States. Pregnancy is a risk factor for deep venous thrombosis, and risk is
      further increased with a personal or family history of thrombosis or
      thrombophilia. Screening for thrombophilia is not recommended for the general
      population; however, testing for inherited or acquired thrombophilic conditions
      is recommended when personal or family history suggests increased risk. Factor V
      Leiden and prothrombin G20210A mutation are the most common inherited
      thrombophilias, and antiphospholipid antibody syndrome is the most important
      acquired defect. Clinical symptoms of deep venous thrombosis may be subtle and
      difficult to distinguish from gestational edema. Venous compression (Doppler)
      ultrasonography is the diagnostic test of choice. Pulmonary embolism typically
      presents postpartum with dyspnea and tachypnea. Multidetector-row (spiral)
      computed tomography is the test of choice for pulmonary embolism. Warfarin is
      contraindicated during pregnancy, but is safe to use postpartum and is compatible
      with breastfeeding. Low-molecular-weight heparin has largely replaced
      unfractionated heparin for prophylaxis and treatment in pregnancy.

PMID- 18619082
TI  - Predicting prognoses in patients with acute stroke.

PMID- 18619083
TI  - Pruritic axillary papules. Fox-Fordyce disease.

PMID- 18619084
TI  - Using health-related quality of life assessments to evaluate care support within
      Medicaid.
AB  - CareOregon, an Oregon-based not-for-profit Medicaid health plan, successfully
      piloted a "CareSupport" model that identifies high-risk members and clinically
      stratifies them for intervention. Internal analyses indicate that CareSupport
      lowers utilization and cost; CareOregon, however, has lacked patient-reported
      outcome data on the health-related quality of life (HRQL) of CareSupport
      participants. Between September 2005 and November 2006, we conducted a pilot
      study in which the Health Utilities Index Mark 3 (HUI3), a generic preference
      based measure of health status and HRQL, was integrated into CareOregon's
      existing screening algorithm for possible admission into CareSupport. We obtained
      baseline data on 616 CareSupport candidates and 4-month HUI3 follow-up data on
      143 candidates (104 CareSupport 39 non-CareSupport). On a 0.00 (dead)-to-1.00
      (perfect health) scale, the mean overall baseline HUI3 score for CareSupport
      patients was 0.18 (0.20 for non-CareSupport patients), comparable to baseline
      means reported elsewhere for much older patients immediately after suffering
      serious acute medical events, such as stroke or hip fracture. A 0.05 mean 4-month
      improvement in overall HRQL among CareSupport enrollees relative to non
      CareSupport enrollees was clinically important but not statistically significant.
      A 0.10 improvement in HUI3 emotion was both statistically significant and
      clinically important. Study results provide good preliminary evidence of the
      value of patient-reported outcomes in clarifying individual illness burden and
      assessing intervention effectiveness.

PMID- 18619085
TI  - Case management and outreach: similarities and differences in worker tasks.
AB  - Case management and outreach are two important services provided to many
      individuals, particularly people with multiple problems. Unfortunately, no
      taxonomy or measuring instrument has been developed that captures the many
      dimensions of the jobs performed by both case managers and outreach workers. This
      study conducted a job analysis that led to the development of an instrument that
      has a variety of potential uses. It can be (a) a method for classifying both case
      management and outreach programs on a number of dimensions that can be used in
      comparing different models of case management and outreach, (b) a means to
      identify specific case management and outreach activities that might be
      correlated with client outcomes, and (c) a tool for developing selection criteria
      as well as performance appraisal dimensions to assess case management and
      outreach work activities.

PMID- 18619086
TI  - Survey of community-based programs serving U.S. families with Huntington's
      disease: perceived barriers and facilitators in the residential placement
      process.
AB  - This article describes the contours of the residential care placement experience
      for social service staff health care providers, and their client families of
      patients with Huntington's disease. The purpose of this study was to determine
      the factors, conditions, and barriers encountered by outpatient clinical staff
      and families in the transition to skilled nursing care. A Long-Term Care Contact
      Survey was developed to (a) gather information about long-term care referral
      sites; (b) determine the factors considered in choosing a facility; (c) describe
      the factors that hindered the transition to long-term care; (d) describe
      conditions prior to institutionalization; and (e) determine research interest.
      The study found that large cohorts of patients with Huntington's disease in
      residential care are scarce. A lack of confidence in the available options
      suggests the need for increased support for educational and social services to
      facility staff Speech/swallowing therapy and physical therapy as placement
      facilitators reflect salient issues of latter stages of the disease, implicating
      funding support needs. Families facing this transition require long-term guidance
      for financiail, caregiving, and psychosocial issues.

PMID- 18619087
TI  - Huntington's disease: a caring approach to the end of life.
AB  - This article describes the challenges of end-of-life care encountered in a
      specialized long-term care program for people with Huntington's disease (HD). The
      Promoting Excellence in End-of-Life Care Huntington's Disease Workgroup defines
      the initiation of palliative care as the point at which independent living is no
      longer possible. Mobility and lifestyle accommodations for people in the nursing
      home setting with an early-onset disease are a major feature of this program. The
      primary end-of-life considerations are advance directives decision-making and
      anticipating end-stage care needs. Disease progression, denial, family conflict,
      and clinician blind-spots may impede the development of timely advance
      directives. The unpredictable and idiosyncratic nature of disease progression
      impacts decision making for end-of-life care settings and approaches:
      hospitalization, nursing home stay, and in-house hospice care are the available
      options. The Workgroup has delineated several priority areas for patient care in
      HD: autonomy; dignity; meaningful social interaction; communication; comfort;
      safety and order; spirituality; enjoyment, entertainment and well-being;
      nutrition; and functional competence. This review also includes a description of
      the program features in each of these areas.

PMID- 18619088
TI  - Too sick to work, too soon for Medicare: the human cost of the 2-year Medicare
      waiting period for Americans with disabilities.
AB  - In the United States, nearly 7 million people under age 65 qualify for Medicare
      due to severe and permanent disabilities. However, these individuals must wait 2
      years after they are deemed eligible for Social Security Disability Insurance to
      receive this coverage. As a result, there are as many as 1.5 million men and
      women who are too disabled to return to work but who must wait to receive
      Medicare coverage for their health care needs. Nearly 39% are uninsured for at
      least some of this time, and 26% have no insurance throughout the waiting period.
      This article tells the stories of three individuals struggling to survive the 24
      month waiting period. These real-life stories expose the financial hardship,
      pain, and suffering caused by the waiting period and provide evidence of the need
      for the swift enactment of legislation to eliminate the waiting period. In this
      article, these individuals give their accounts of what it means to become too
      sick or disabled to work, and to learn that it is too soon to get health care
      coverage through Medicare. In all cases, we have tried to stay as close as
      possible to the language and the spirit of the participants' stories.

PMID- 18619089
TI  - Group homes for elders with dementia in Japan.
AB  - In this article we explore the development of group homes for elders with
      dementia in Japan since the inception of the long-term care insurance program in
      2000. We suggest that the combination of demographic and policy trends in recent
      years have created a context in which entrepreneurial activities related to elder
      care have increased significantly. By focusing on one of the new institutions
      that has emerged, we show one way in which social policy has had a significant
      influence on the lives of elders suffering from dementia and their families.
      Finally, we point out some of the problems that have arisen along with the growth
      of these new forms of care, such as a lack of involvement by family members in
      visiting and caring for elders.

PMID- 18619090
TI  - Liver isolation in abdominal MRI.
AB  - This work presents a method for liver isolation in magnetic resonance imaging
      (MRI) abdomen images. It is based on a priori statistical information about the
      shape of the liver obtained from a training set using the segmentation approach.
      Morphological watershed algorithm is used as a key technique as it is a simple
      and intuitive method, producing a complete division of the image in separated
      regions even if the contrast is poor, and it is fast, with possibility for
      parallel implementation. To overcome the over-segmentation problem of the
      watershed process, image preprocessing and postprocessing are applied.
      Morphological smoothing, Gaussian smoothing, intensity thresholding, gradient
      computation and gradient thresholding are proposed for preprocessing with
      morphological and graph based region adjacent list constructed for region
      merging. A new integrated region similarity function is also defined for region
      merging control. The proposed method produces good isolation of liver in axial
      MRI images of the abdomen, as is shown in this paper.

PMID- 18619091
TI  - Physician and nurse job climates in hospital-based emergency departments in
      Taiwan: management and implications.
AB  - This study evaluates how emergency physicians and nurses perceive their job
      climates in their hospital-based emergency departments (ED). In total, 208
      emergency physicians and 234 emergency nurses were surveyed, applying a validated
      survey instrument covering the job facets of medical and nursing autonomy,
      professional accomplishments and outcomes, leadership, communication, management,
      hospital policies and regulations, and external health policy environments
      germane to emergency medicine. The findings reveal that the average satisfaction
      score for professional growth and accomplishments was ranked highest by emergency
      physicians, and job communication within EDs was ranked highest by emergency
      nurses. Several emergency medical professional characteristics, including age,
      education, medical authority, employment duration, full-time or part-time
      statuses, perceived workloads, and hospital accreditation levels, were all
      related to job satisfaction in this surveyed population. New insights generated
      from this study could provide increased guidance to hospital and ED unit managers
      toward enhancing wellness and limiting dissatisfaction and disharmony relative to
      long-term career survival and the well-being of ED specialists.

PMID- 18619092
TI  - Computer simulation of heat transfer in different tissue layers of body
      extremities under heat stress in deep anesthetic condition.
AB  - Many mathematical models of thermoregulation in humans have been developed, so
      far. These models appeared to be very useful tools for studying temperature
      regulation in humans under adverse environmental conditions. However, no one
      discussed the heat transfer characteristics of denervated subjects. Thus, the
      present study is concerned with aspects of the passive system for denervated
      subjects: (1) modeling the human body extremities (2) modeling heat transport
      mechanism within the body and at its periphery. The present model was simulated
      using the software (Wintherm 8.0, Thermoanalytics, USA) for different body
      segments to predict the heat flow between body core and skin surface with changes
      in environmental temperature with fixed relative humidity and wind velocity. The
      simulated model for comparative study of internal temperature distribution of
      hand, arm, leg and feet segments yielded remarkably good results and observed to
      be in trends with previously cited work under ambient environmental condition and
      at controlled room temperature. Models could be used to measure the temperature
      distribution in human limbs during local hyperthermia and to investigate the
      interaction between limbs and the thermal environment.

PMID- 18619093
TI  - Artificial neural network and wavelet based automated detection of sleep
      spindles, REM sleep and wake states.
AB  - Backpropagation artificial neural network (ANN) has been designed to classify
      sleep-wake stages. Four hours continuous three channel polygraphic signals such
      as EEG (electroencephalogram), EOG (electrooculogram) and EMG (electromyogram)
      from conscious subjects were digitally recorded and stored in computer. EOG and
      EMG signals were used for manual identification of sleep states before training
      and testing of ANN. The percentages power of the 2 s epochs of the digitized EEG
      signals from each of three sleep-wake patterns, sleep spindles (SS), rapid eye
      movement (REM) sleep and awake (AWA) sates, were calculated and analyzed to
      select the manually confirmed sleep-wake states for each epoch. Further, second
      order Daubechies mother wavelet has been used to get the wavelet coefficients for
      the selected EEG epochs. The wavelet coefficients for the EEG epochs (64 data)
      were selected as inputs for the training the network and to classify SS, REM
      sleep and AWA stages. The ANN architecture used (64-14-3) in present study shows
      overall very good agreement with manual sleep stage scoring with an average of
      95.35% for all the 1,140 samples tested from SS, REM and AWA stages. This
      architecture of ANN was also found effectively differentiating the EEG power
      spectra from different sleep-wake states (96.84% in SS, 93.68% in REM sleep,
      95.52% in AWA state). The high performance observed with the system based on
      wavelet coefficients along with the ANN, highlights the need of this
      computational tool into the field of sleep research.

PMID- 18619094
TI  - Imaging systems of human eye: a review.
AB  - The eyes are complex sensory organs and are designed to optimize vision under
      conditions of varying light. There are a number of eye disorders that can
      influence vision. Eye disorders among the elderly are a major health problem.
      With advancing age, the normal function of eye tissues decreases and there is an
      increased incidence of ocular pathology. The most common causes of age related
      eye disorder and visual impairment in the elderly are cataracts and primary open
      angle glaucoma. Different imaging systems are available to visualize the
      different parts of the eye non-invasively with higher accuracy. This paper
      discusses the various techniques available namely, computed tomography, confocal
      laser scanning microscopy, magnetic resonance imaging, optical coherence
      tomography, ultrasound imaging, infrared thermography for the imaging of the
      different eye abnormalities.

PMID- 18619095
TI  - Military medical graduates' perceptions of organizational culture in Turkish
      military medical school.
AB  - Organizational culture is the term used to describe the shared beliefs,
      perceptions, and expectations of individuals in organizations. In the healthcare
      environment, organizational culture has been associated with several elements of
      organizational experience that contribute to quality, such as nursing care, job
      satisfaction, and patient safety. A range of tools have been designed to measure
      organizational culture and applied in industrial, educational, and health care
      settings. This study has been conducted to investigate the perceptions of
      military medical graduates on organizational culture at Gulhane Military Medical
      School. A measurement of organizational culture, which was developed by the
      researchers from Akdeniz University, was applied to all military medical
      graduates in 2004. This was a Likert type scale that included 31 items. Designers
      of the measurement grouped all these items into five main dimensions in their
      previous study. The items were scored on a five-point scale anchored by 1:
      strongly agree and 5: strongly disagree. Study participants included all military
      physicians who were in clerkship training period at Gulhane Military Medical
      Academy in 2004. A total of 106 graduates were accepted to response the
      questionnaire. The mean age of participants was 25.2 +/- 1.1. At the time of
      study only 8 (7.5%) graduates were married. The study results have showed that
      the measurement tool with 31 items had a sufficient reliability with a Cronbach's
      alpha value of 0.91. Factor analysis has resulted a final measurement tool of 24
      items with five factors. Total score and the scores of five subdimensions have
      been estimated and compared between groups based on living city and marital
      status. The study has shown the dimension of symbol received positive perceptions
      while the dimension of organizational structure and efficiency received the most
      negative perceptions. GMMS has a unique organizational culture with its weak and
      strong aspects. Conducting this kind of studies contribute to improve
      organizational culture in order to increase educational and research capability.

PMID- 18619096
TI  - A new method to guard inpatient medication safety by the implementation of RFID.
AB  - Since life is invaluable, the patient safety is always an important issue. How to
      reduce the malpractices and advance the patient safety is the primary goal of
      many countries. The current problem is that the hospitals cannot quickly and
      precisely identify the name of medicine, the position of patient and staff and
      the servicing time and dosage taken by patients. The application of Radio
      Frequency Identification (RFID) is rocketing in popularity as varieties of
      expanded uses. However, due to the investment consideration, there are few cases
      that practically implement such a technology in healthcare industries. This paper
      presents a Wisely Aware RFID Dosage (WARD) system, which based on an integration
      of barcodes and RFID tags, to demonstrate effective and safe patient care
      environment, for preventing the risk of medication error. Finally, through an
      evaluation of users' satisfaction, a reliability of 0.92 and a criterion-related
      validity of 0.82 show that this system is able to effectively construct the
      patient-safety-centric environment.

PMID- 18619097
TI  - A proposed instrument for the assessment of job satisfaction in Greek mental NHS
      hospitals.
AB  - Since its introduction in 1983, the Greek NHS is under an almost constant reform,
      aiming improvement on the efficiency and the quality of provided services. The
      national program of psychiatric reform "Psychargos" introduced new models of
      therapeutic approach to the care of the mentally ill, that required expansion of
      the existing roles and development of new roles of the healthcare staff.
      Consequently, the efficient management of the healthcare workforce in Greek
      mental facilities was identified as a primary determinant of the successful
      implementation of the program. Primary objective of this study was the
      development of a research framework for the assessment of job satisfaction in
      Greek Mental Health Hospitals. Among the objectives was the evaluation of the
      capacity of the underlying motivators and hygiene factors and the identification
      of potential correlations of the global job satisfaction and the motivation and
      retention factors with the demographic, social and occupational characteristics
      of the employees. A custom questionnaire was developed, based on Herzberg two
      factor theory, after a systematic review of the relevant literature. The
      instrument was constructed by two parts and 37 items. Ten items addressed the
      sociodemographic characteristics of the subjects, while the remaining 27 items
      were distributed in 11 subscales which addressed the global satisfaction index
      and the "retention" and the "motivation" variables. The instrument was validated
      by means of the Cronbach alpha for each subscale and by confirmatory factor
      analysis. The study was conducted at the Public Mental Hospital of Chania (PMHC).
      From the 300 employees of the PMHC, 133 subjects successfully responded to the
      questionnaire (response rate, 44.3%). In accordance to former surveys, subjects
      presented average scores in the global satisfaction index (GSI). The professional
      category of the employee was identified as the primary determinant of the GSI.
      Nurses presented statistically significant lower scores in comparison to the rest
      of the employees. Strong Pearson correlations were detected between GSI and
      "working conditions", "interpersonal relations", "organization", "salary" and
      "supervision" factors. The retention factors presented stronger impact on GSI in
      comparison to the motivation ones. The results of the study indicate that the
      proposed instrument presents satisfactory validity and reliability for the
      assessment of job satisfaction in Greek mental NHS hospitals.

PMID- 18619098
TI  - Determinants of hospital choice of rural hospital patients: the impact of
      networks, service scopes, and market competition.
AB  - Among 10,384 rural Colorado female patients who received MDC 14 (obstetric
      services) from 2000 to 2003, 6,615 (63.7%) were admitted to their local rural
      hospitals; 1,654 (15.9%) were admitted to other rural hospitals; and 2,115
      (20.4%) traveled to urban hospitals for inpatient services. This study is to
      examine how network participation, service scopes, and market competition
      influences rural women's choice of hospital for their obstetric care. A
      conditional logistic regression analysis was used. The network participation (p <
      0.01), the number of services offered (p < 0.05), and the hospital market
      competition had a positive and significant relationship with patients' choice to
      receive obstetric care. That is, rural patients prefer to receive care from a
      hospital that participates in a network, that provides more number of services,
      and that has a greater market share (i.e., a lower level of market competition)
      in their locality. Rural hospitals could actively increase their competitiveness
      and market share by increasing the number of health care services provided and
      seeking to network with other hospitals.

PMID- 18619099
TI  - The programmable ECG simulator.
AB  - This paper reports the design and development of Digital Signal Controller
      (DSPIC)-based ECG simulator intended to use in testing, calibration and
      maintenance of electrocardiographic equipment, and to support biomedical
      engineering students' education. It generates all 12 healthy ECG derivation
      signals having a profile that varies with heart rate, amplitude, and different
      noise contamination in a manner which reflects true in vivo conditions. The heart
      rate can be set at the range of 30 to 120 beats/minute in four steps. The noise
      and power line interference effects can be set at the range of 0 to 20 dB in
      three steps. Since standard commercially available electronic components were
      used to construct the prototype simulator, the proposed design was also
      relatively inexpensive to produce.

PMID- 18619100
TI  - Connecting health insurance to quality of medical care.

PMID- 18619101
TI  - The lesion on this patient's tongue really hurts.

PMID- 18619102
TI  - Come hear, baby! Identifying and managing congenital hearing loss.

PMID- 18619103
TI  - Severe hyponatremia develops in a runner following a half-marathon.

PMID- 18619104
TI  - Examining modern approaches to inguinal and femoral herniorrhaphy.

PMID- 18619105
TI  - Hypothermia: a cool intervention for hypoxic-ischemic encephalopathy.

PMID- 18619106
TI  - Diverticular disease of the colon: a conservative approach works best.

PMID- 18619107
TI  - Homeless, housed, and homeless again.

PMID- 18619108
TI  - A relatively common cause of pain in the hand.

PMID- 18619109
TI  - Case of the month. Cauda equina syndrome.

PMID- 18619110
TI  - Resolution of neurological DCI after long treatment delays.
AB  - We report two interesting cases in which both divers sustained a very serious
      Type II decompression sickness. This involved substantial neurological impairment
      which was successfully treated despite having a delayed treatment time 12 hours
      or more. The treatment used hyperbaric oxygen recompression therapy with the
      addition oflidocaine i.v. drip. This first case was in November 2007 and the
      second was in December 2007 and both patients made excellent recoveries.

PMID- 18619111
TI  - Barotraumatic orbital emphysema of rhinogenic origin in a breath-hold diver: a
      case report.
AB  - Orbital emphysema is a well-recognized complication of fractures involving the
      orbit. Commonly, it occurs when high pressure develops in nasal cavity as during
      nose blowing, coughing or Valsalva's maneuver and usually occurs in the
      subcutaneous tissues. We report the case of a young breath-hold diver who
      developed spontaneous, non compressive orbital emphysema during underwater
      fishing, with a maximal depth of 25-30 meters in the Sardinian sea. He was
      otherwise healthy, without previous cranio-facial trauma and nasosinusal diseases
      or surgery were not present in the history. When he was referred to our attention
      the patient presented right eyelid ptosis but diplopia and vision impairment were
      absent. Computer tomography scans showed subcutaneous air in the right upper
      eyelid and around the eyeball, particularly near the orbit's roof but optic nerve
      area, intraconal, was free of air. A dehiscence in lamina papyracea was evident.
      In our opinion, this has been the point of air entry into the orbit. A supportive
      therapy was advised and two weeks later the emphysema was recovered completely
      and the subject was symptoms free. The literature has been revised and to our
      knowledge no previous cases of barotraumatic orbital emphysema, in a breath-hold
      diver, are referred.

PMID- 18619112
TI  - Conjunctivitis outbreak among divers.
AB  - In March 2006, an outbreak of conjunctivitis that occurred over a six day period
      among twenty-nine individuals who partook in recreational scuba diving trips on
      two boats off Vitu Levu Island, Fiji. We investigated the likelihood that a
      communal container used to store diving masks facilitated the spread of
      conjunctivitis among individuals. The diagnosis of conjunctivitis was based on
      clinical assessment by a physician. Transmission of conjunctivitis from person to
      person was documented with eventual identification of the index case, the dive
      master, a Fijian resident. Topical antibiotics were dispensed accordingly and
      detergent and bleach were used as mask cleaning agents in an effort to control
      the outbreak. Follow up surveys were mailed to all twenty-nine participants.
      Ultimately, fourteen cases of conjunctivitis were documented (46.7%). Eleven
      cases were verified during the six days in Fiji, two upon arrival back in the
      U.S., and one case of familial transmission in the U.S. All but two cases
      resolved within one week. Unknown to these divers was a coincidental, generalized
      outbreak of acute haemorrhagic conjunctivitis among the Fijian Residents. The
      communal container used to store diving masks was the likely vector for the
      spread of infectious conjunctivitis, the first such documented outbreak involving
      communal diving equipment.

PMID- 18619113
TI  - Subjective and behavioural responses to nitrogen narcosis and alcohol.
AB  - RATIONALE: There is a widespread assumption that nitrogen narcosis is comparable
      to alcohol intoxication, a similarity that may extend to patterns of tolerance.
      It has been suggested this indicates evidence of a shared biological mechanism
      but there is a paucity of experimental data to support these claims. OBJECTIVE:
      The current study aimed to test this assumption by comparing subjective (ratings)
      and behavioural (Digit Letter Substitution Test) responses to nitrogen narcosis
      and alcohol. METHODS: Experiment 1 compared responses to narcosis in 39
      participants posited to differ in tolerance based on prior exposure to alcohol
      (heavy/light drinkers) and narcosis (novice/experienced divers). Experiment 2
      compared responses to narcosis and after a 0.5 g/kg dose of alcohol in 23
      participants. In both experiments narcosis was measured at depths between 40 and
      45m in the ocean off Port Vila, Vanuatu. RESULTS: Experiment 1 measured a
      significant decrement in the behavioural measure underwater, compared to baseline
      but failed to find any differential responding to narcosis between drinker or
      diving experience groups. In contrast, Experiment 2 found positive correlations
      between alcohol and narcosis on both subjective and behavioural measures,
      indicating those affected to a greater degree by alcohol were also affected to a
      greater degree by narcosis. CONCLUSIONS: These results support the contention of
      a relationship between nitrogen narcosis and alcohol, although the role of diving
      and drinking history, if any, remains obscure.

PMID- 18619114
TI  - Respiratory muscle training improves swimming endurance at depth.
AB  - Respiratory muscle training (RMT) has been shown to improve divers swimming
      endurance at 4 feet of depth; however, its effectiveness at greater depths, where
      gas density and the work of breathing are substantially elevated has not been
      studied. The purpose of this study was to examine the effects of resistance
      respiratory muscle training (RRMT) on respiratory function and swimming endurance
      at 55 feet of depth (270.5 kPa). Nine male subjects (25.9 +/- 6.8 years)
      performed RRMT for 30 min/day, 5 d/ wk, for 4 wks. Pre- and Post RRMT, subjects
      swam against a pre-determined load (70% VO2 max) until exhausted. As indices of
      respiratory muscle strength, maximal inspiratory and expiratory pressures were
      measured before and immediately following the swims pre- and post-RRMT. These
      measurements showed that ventilation was significantly lower during the swims
      and, at comparable swim duration, that the respiratory muscles were considerably
      less fatigued following RRMT. The reduced ventilation was due to a lower
      breathing frequency following RRMT. The ventilatory changes following RRMT
      coincided with significantly increased swimming time to exhaustion (approximately
      60%, 31.3 +/- 11.6 vs. 49.9 +/- 16.0 min, pre- vs. post-RRMT, p < 0.05). These
      results suggest respiratory muscle fatigue limits swimming endurance at depth as
      well as at the surface and RRMT improves performance.

PMID- 18619115
TI  - Prevalence of patent foramen ovale (PFO) and MRI-lesions in mild neurological
      decompression sickness (type B-DCS/AGE).
AB  - BACKGROUND: Neurological decompression sickness (DCS/AGE) may cover two variants
      with either severer and probably central nervous (Type A) or milder and sometimes
      doubtful neurological symptoms (Type B). The pathophysiology of the Type B
      DCS/AGE might be different from the Type A-variant. In Type A-DCS/AGE a higher
      PFO-prevalence (patent foramen ovale) points towards an embolic origin of the
      Type A-symptomatology. This is not necessarily expected for the Type B-DCS/AGE if
      the pathophysiology here is micro-embolic or even non-embolic. METHODS: 18
      patients with Type B-DCS/AGE were tested against matched controls for presence
      and size of a PFO with echocardiography and transcranial ultrasound with echo
      contrast. Prevalence and number of Type A-brain lesions were visualized by
      cranial MRI as possible sequelae from gas-embolic events. RESULTS: PFO-prevalence
      in both groups, the patients with Type B-DCS/AGE (5/18) as well as the controls
      (7/18) was similar to published PFO-prevalences in normals without any difference
      between patients and controls (p = 0.725). Also the number of MRI-lesions (ACFs)
      was the same for Type B-DCS/AGE cases (15 ACFs in 5 patients) and controls (37
      ACFs in 8 divers). CONCLUSION: Indirect findings suggesting embolic brain
      injuries are found with similar frequency in patients with Type B-DCS/AGE and
      normal controls, which is in contrast to data about Type A-DCS/AGE. This is
      compatible with different pathophysiological mechanisms involved in the Type A-
      and Type B-DCS/AGE.

PMID- 18619116
TI  - Underutilization of echocardiography for patent foramen ovale in divers with
      serious decompression sickness.
AB  - The presence of a patent foramen ovale (PFO) in compressed gas diving has been
      considered a risk factor for serious decompression illness (DCS) for more than 20
      years. We conducted a ten year retrospective chart review aimed at determining if
      physicians treating DCS in a university medical center setting used
      echocardiography to assess PFO in patients with severe DCS, and if so whether PFO
      is over-represented in that population. Over the ten-year period, 113 divers
      underwent recompression therapy for decompression sickness. Of these patients, 48
      had serious DCS defined by at least one objective neurological finding. We
      reviewed medical records for the presence of agitated saline contrast
      echocardiogram testing and whether or not PFO was present. Only 12 of 48 patients
      with serious DCS underwent transthoracic agitated saline contrast echocardiogram
      testing. Of these 12 patients, 6 (50%) had a resting PFO. Binomial proportion
      testing yielded 95% confidence limits of 21% and 79%. Given 27% PFO prevalence in
      the general population, PFO may be over-represented in our group of most
      seriously injured DCS patients yet 75% of patients with objective neurological
      signs did not undergo echocardiography.

PMID- 18619117
TI  - The effect of over- or underfilling the soda lime canister on CO2 absorption in
      two closed-circuit oxygen rebreathers.
AB  - O2 diving incidents investigated by our laboratory were related to improper
      filling of the soda lime canister in closed-circuit oxygen rebreathers. We
      studied the effect of overfilling or underfilling the canister on CO2 absorption
      using a continuous flow of 5% CO2. With a full canister in the Oxyger 57, CO2
      began to rise at 130-160 min, reaching 1% at 240 min and 1.5% at 270 min. Similar
      results were obtained after a reduction of 100 g in the quantity of soda lime
      packed into the canister. After reductions of 200, 300 and 400 g, the rise in CO2
      concentration occurred earlier as a function of the amount of the reduction. The
      level of CO2 in the OxyNG 2 began to rise after 250 min with a full canister,
      reaching 1% at 340 min and 1.5% at 370 min. After a reduction of 100 g there was
      a delay in the rise of CO2, which reached 1.5% at 390 min. However, when the
      reduction was 200, 300 and 400 g, the rise in CO2 concentration tended to occur
      earlier as a function of the amount of the reduction. For both rebreathers, when
      the quantity of soda lime was reduced by 200 g or more, there was a considerable
      difference in timing between the two test measurements for each weight reduction,
      due to variations in channeling. For an excess of soda lime, moderate pressure
      was applied manually to achieve a full canister plus 300 g in the OxyNG 2. The
      initial rise in CO2 concentration started early, at 60 min with a full canister
      plus 300 g compared to 150 min with a full canister; 1% CO2 was reached at 120
      min, compared to 210 min with a full canister. As the use of rebreathers becomes
      increasingly widespread in diving, close attention should be paid to proper
      filling of the soda lime canister.

PMID- 18619118
TI  - Validation of hyperbaric oxygen treatment software for use with monoplace
      chambers.
AB  - Hyperbaric oxygen (HBO2) therapy is increasingly used in the treatment of a wide
      variety of medical conditions. However, for monoplace chambers, there is some
      uncertainty when sufficiently high oxygen concentrations are attained, because
      most chambers are not instrumented to measure oxygen. To remedy this, Microsoft
      Excel-based software, HBO O2 Smart Guide, was developed to simulate the
      atmosphere ofmonoplace chambers during treatment. Based upon chamber dimensions,
      patient weight, oxygen purge rates, desired pressurization, and HBO2 time, the
      program calculates oxygen concentration, consumption and exposure for each
      treatment. Software testing was conducted using four different chambers
      instrumented with an oxygen analyzer. Two purge rate profiles were used:
      constant, and biphasic (a high initial purge rate was changed to a lower plateau
      rate when pressurization was reached). Comparison of measured and calculated
      times to reach 95% oxygen concentration within the chambers demonstrated the
      software was accurate within 1%. The HBO O2 Smart Guide enables optimum purge
      profiles to be simulated with resultant potential improvements in HBO2 treatment
      efficacy, calculation of effective oxygen exposures (actual time during
      prescribed treatment during which patient breathes > or = 95% oxygen) to enable
      more accurate comparison of treatment profiles and outcomes, and cost savings in
      oxygen usage. This software will enable clinicians to provide more consistent
      HBO2 treatments.

PMID- 18619119
TI  - Role of tumor markers and circulating tumors cells in the management of breast
      cancer.
AB  - Along with various imaging modalities, serologic tumor markers such as CA 15-3
      and CA 27.29 have been used for decades to monitor treatment response in patients
      with metastatic breast cancer (MBC). Despite the frequent use of these markers,
      they lack high sensitivity and specificity for breast cancer progression. The
      prognostic significance of these markers remains indeterminate because of the
      conflicting outcome of many clinical trials. The circulating tumor cell (CTC)
      test has recently been studied in clinical trials in patients with MBC. Some of
      the studies showed that high levels of CTCs are correlated with poor survival in
      MBC. An intergroup trial is underway to determine the implication of changing
      treatment based on the CTC level. This article will discuss the current data on
      these markers, with special emphasis on the CTC test. The potential clinical
      utility of these markers will also be discussed.

PMID- 18619120
TI  - Proton-beam vs intensity-modulated radiation therapy. Which is best for treating
      prostate cancer?
AB  - There is a growing interest in the use of proton therapy for the treatment of
      many cancers. With its unique dose-distribution properties, proton therapy has
      the potential to improve the therapeutic ratio of prostate radiation by allowing
      for an increase in dose without a substantial increase in side effects. While
      much evidence supports this notion in the context of many oncologic sites, only
      limited clinical data have compared protons to photons in prostate cancer.
      Therefore, the increasing enthusiasm for the use of protons in prostate cancer
      has aroused considerable concern. Some have questioned its ability to limit
      morbidity, and others have questioned its value relative to the cost. In
      addition, theoretical concerns have been raised about a potential additional risk
      for secondary malignancies. In this article, we review the current status of the
      evidence supporting the use of protons in prostate cancer and discuss the active
      controversies that surround this modality.

PMID- 18619121
TI  - Stereotactic body radiotherapy in the management of painful bone metastases.
AB  - More than 100,000 new cases of bone metastases are diagnosed each year, and they
      present an important clinical problem. They cause significant morbidity and
      quality-of-life issues in cancer patients. Conventional external-beam
      radiotherapy is currently the most common method to treat these metastases, with
      several randomized controlled trials showing no difference in effectiveness
      between multiple- and single-dosing treatment regimens. A newer technology to
      treat bone metastases is stereotactic body radiotherapy (SBRT), a radiation
      delivery method that allows for a large ablative dose to be accurately given to
      the target over one to a few fractions. This review details the role of SBRT in
      painful bone metastases, primarily in the vertebral column, but in other bony
      sites as well, its unique advantages and disadvantages, and its role in the
      treatment of tumors traditionally deemed radioresistant. Toxicity to surrounding
      normal tissues and patterns of local failures are also addressed.

PMID- 18619122
TI  - Neoadjuvant chemoradiation for rectal cancer: is more better?
AB  - Neoadjuvant chemoradiation is now considered the clear preferable adjuvant
      standard of care in the management of stage II/III rectal cancer. Neoadjuvant
      fluorouracil (5-FU) plus radiation results in a decrease in local relapse rates
      and a favorable toxicity profile in comparison with postoperative adjuvant 5-FU
      plus radiation therapy. Recent nonrandomized comparative studies have shown that
      capecitabine (Xeloda) plus radiation result in downstaging and pathologic
      complete responses equivalent to those of 5-FU plus radiation, making this
      combination an acceptable alternative neoadjuvant treatment. The addition of
      oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine
      concurrently with radiation therapy appears to result in more favorable
      pathologic responses in phase I/II trials. These combinations should be
      investigated further in larger phase III studies before they are endorsed in the
      routine neoadjuvant treatment of rectal cancer. This article will review the
      progress of chemoradiation over the past 2 decades, current standards of care,
      and investigational treatments in the neoadjuvant treatment of rectal cancer.

PMID- 18619123
TI  - Pharmacological agents for the prevention and treatment of toxic radiation
      exposure in spaceflight.
AB  - BACKGROUND: Astronauts are exposed to toxic ionizing radiation sources, including
      galactic cosmic radiation and solar particle events (SPE). Exposure to these
      radiation sources can lead to cataracts, heritable genetic mutations, cancer,
      acute life-threatening physiological compromise, and death. Current
      countermeasures focus on spacecraft shielding and creation of heavily shielded
      safe havens. At issue is the extraordinarily high cost of launching these heavy
      structures into space and their inability to provide adequate shielding from
      heavy ions at a feasible shield thickness. Pharmacological enhancement of
      cellular radiation resistance, an alternative method to limiting radiation
      toxicity, has received less attention. METHODS: We have conducted an extensive
      literature review and critical evaluation of the scientific data pertaining to
      this field of study. Publications for review were identified through a Medline
      search using relevant terms, including radiotherapeutics, galactic cosmic
      radiation, radiopharmacology, radioprotectants, radiation countermeasures, solar
      particles, solar flares, radiation toxicity, and radiotoxicity. RESULTS: We
      identified 15 agents with significant radiation dose reduction factors, ranging
      from 1.1 to 2.4, in experimental models. Of these, only amifostine is FDA
      approved for use in treating radiation toxicity. CONCLUSIONS: Current data do not
      support the use of radiopreventive agents in the treatment of low-level ionizing
      radiation exposures. However, pharmacological countermeasures should be
      instituted for life-threatening, high-level radiation exposures, as occur with
      SPE. Given the catastrophic effects of SPE, the risk of toxicity from
      radioprotective agents is warranted. The current data supports treatment with
      high-dose amifostine (at 910 mg m(-2)) 30 min prior to radiation exposure.

PMID- 18619124
TI  - Nauseogenicity of off-vertical axis rotation vs. equivalent visual motion.
AB  - INTRODUCTION: Off-vertical axis rotation (OVAR) provokes motion sickness. The
      visual motion equivalent to OVAR in simulators is also nauseogenic. Our
      experiment compared the nauseogenicity of OVAR vs. visual motion. METHODS: There
      were 12 subjects who undertook the following conditions: A) OVAR in darkness at
      0.2 Hz, 18 degrees tilt; B) same OVAR with eyes open in the light; and C)
      stationary, seated upright, watching a video of the visual motion experienced in
      B. The conditions were counterbalanced and performed at the same time of day with
      a minimum 5-d separation between conditions. Stimulation was stopped at moderate
      nausea with a 20-min maximum cut-off. Motion sickness susceptibility was rated on
      a standardized questionnaire (MSSQ). RESULTS: Time (mean +/- SD minutes) to
      moderate nausea was significantly shorter for real OVAR conditions (A: 7.1 +/-
      5.5; B: 7.7 +/- 6.7) vs. video (C: 15.7 +/- 6.4). Subjects with relatively low
      susceptibilities to motion sickness developed nausea more slowly with vision (B-A
      time difference correlated with MSSQ scores r = -0.7, P < 0.05). Headache was
      more prominent with visual field motion (C). CONCLUSIONS: OVAR was twice as
      nauseogenic as visual motion. Headache during visual motion suggests mechanisms
      in common with migraine. We hypothesize that subjects who fared better in the
      light used visual cues to resolve sensory conflict, whereas subjects who were
      equally susceptible in light and dark made poor use of visual cues; perhaps a
      form of 'field dependency'. This may explain why some people prefer 'a view of
      the road ahead' to help against motion sickness whereas others shut their eyes.

PMID- 18619125
TI  - Visual fields during acute exposure to a simulated altitude of 7620 m.
AB  - BACKGROUND: The hypoxia associated with sudden exposure to high altitude is known
      to impair vision and may thereby affect flight safety. However, no data were
      available regarding hypoxic effects on visual fields. The aim of this study was
      to evaluate black-and-white visual field sensitivity with acute hypoxia during
      acute exposure to a simulated altitude of 7620 m. METHODS: Subjects were 15 male
      pilots 26-39 yr of age. We measured arterial oxygen saturation (S(aO2)%) using
      transdermal pulse oximetry while the visual field was measured within a 30
      degrees eccentricity in the right eye by computerized perimetry. The subject
      breathed 100% O2 for 30 min before and during chamber ascent, then removed his
      mask while measurements were performed. RESULTS: The S(aO2)% and visual field
      sensitivities (mean +/- SD) at ground level were 99.1 +/- 0.4% and 43.9 +/- 2.1
      dB, respectively. During hypoxia, the S(aO2)% dropped to 64.0 +/- 5.4% within 3
      min. Mean visual sensitivity was significantly reduced by 7.2 +/- 1.6 dB.
      Furthermore, peripheral sensitivity was slightly but significantly more
      diminished than central sensitivity. CONCLUSIONS: Severe acute hypoxia reduces
      central and moderate peripheral black-and-white vision by a factor of two with
      the strongest effect in the periphery.

PMID- 18619126
TI  - Combat stress or hemorrhage? Evidence for a decision-assist algorithm for remote
      triage.
AB  - INTRODUCTION: In the setting of remote military triage, when physical access to
      the patient is not possible, traditional physiological measurements available to
      a combat medic may not differentiate between a wounded soldier and an active
      soldier. We tested the hypothesis that changes in high-frequency R-R interval
      spectral power (RRI HF) and pulse pressure (PP) would differ between progressive
      central hypovolemia (simulated hemorrhage) and exercise to evaluate their
      potential for remotely distinguishing active from bleeding soldiers. The RRI HF
      and PP were used because of their ability to track central hypovolemia. METHODS:
      There were 12 (8 female/4 male) healthy, normotensive, nonsmoking subjects (age
      27 +/- 2 yr; height 169 +/- 3 cm; weight 68 +/- 5 kg) who were exposed to
      progressive lower body negative pressure (LBNP) and a supine cycle ergometer
      protocol. ECG and blood pressure were measured continuously. Exercise workloads
      were determined by matching the heart rate (HR) responses to each LBNP level.
      Data were analyzed in time and frequency domains. RESULTS: HR increased from 67
      +/- 3 bpm at rest to 101 +/- 4 bpm by -60 mmHg LBNP and was matched within 5%
      during exercise. By the final stage, RRI HF decreased by a similar magnitude
      during both LBNP (-78 +/- 7%) and exercise (-85 +/- 6%). PP decreased by 30 +/-
      4% with LBNP compared with an increase of 20 +/- 6% during exercise. CONCLUSION:
      Monitoring PP in combination with RRI HF would distinguish a bleeding from an
      active soldier. Technologies that incorporate telemetry to track these derived
      vital signs would provide a combat medic with remote decision support to assess
      soldier status on the battlefield.

PMID- 18619127
TI  - Effects of airsickness in male and female student pilots: adaptation rates and 4
      year outcomes.
AB  - INTRODUCTION: Airsickness (AS) often affects aircrew members, especially at the
      beginning of their flight careers. In this study the AS incidence in 376 Italian
      Air Force student pilots (336 men and 40 women) was investigated during their
      initial flight activity. METHODS: The study was separated into two parts. In part
      1, the AS incidence was analyzed in the whole sample to determine the overall
      characteristics of AS and the hypothetical differences between men and women
      during the first flight certification (Basic). Part 2 analyzed a subpopulation of
      102 individuals (86 men, 16 women) over 4 subsequent years throughout the first 4
      flight certifications (for a total of about 60 flight hours). In all cases, AS
      was evaluated according to the number of flight missions affected by vomiting
      episodes. RESULTS: The overall AS incidence during Basic was 34.8%, without
      significant gender differences. However, within AS individuals, a significantly
      higher percentage of women were slow adaptors (12.5% of the whole female sample
      vs. 3.3% in men). AS overall affected the likelihood of reaching Basic
      certification, but this was not significantly related to the number of AS
      episodes. The 1-yr interval between two subsequent flight certifications caused a
      loss of adaptation to the flight environment in most cases. DISCUSSION: The
      absolute incidence of AS in our study resulted within the expected range, without
      significant differences between men and women. In a minor number of individuals
      (11 out of 336 men and 5 out of 40 women) a slow capability of adaptation to AS
      was observed. Such a finding was statistically more prevalent in women. In
      contrast to previous literature data, when prolonged interruptions from flight
      activity are planned, the retention of adaptation in our study did not play a
      significant role in avoiding future episodes of AS.

PMID- 18619128
TI  - Spinal MRI in fighter pilots and controls: a 13-year longitudinal study.
AB  - INTRODUCTION: Although it is known that some degenerative changes occur in the
      spines of fighter pilots, it is not clear whether their frequent exposure to high
      acceleration is associated with premature development of such changes. This case
      control study was designed help answer that question. METHODS: There were 12
      Finnish Air Force pilot cadets and their controls who were examined using
      cervical and lumbar magnetic resonance imaging (MRI) before the pilots started
      fighter training (baseline) and 13 yr later (follow-up) when the pilots had
      accumulated a total of 1200 +/- 470 h in fighter aircraft. RESULTS: No
      statistical differences were found between groups with respect to the frequency
      of degenerative changes in either the cervical or lumbar spine. Cervical changes
      in pilots were for the most part observed in the lower part of the neck, while
      controls showed more variability as to location. In the lumbar region, pilots
      showed a non-significant tendency toward more changes in disks L4-S1, including
      changes in signal intensity, height, protrusions, and end plates. CONCLUSION:
      Occupational exposure to acceleration in fighter aircraft did not cause
      significant radiological changes in the spinal column during the first 13 yr of a
      fighter pilot's flying career. Assessments for the need of a fighter pilot's
      follow-up imaging should be based on clinical outcome, not on periodic imaging.

PMID- 18619129
TI  - Injury risk factors in parachuting and acceptability of the parachute ankle
      brace.
AB  - INTRODUCTION: This investigation examined risk factors for injuries during
      military parachute training and solicited attitudes and opinions regarding a
      parachute ankle brace (PAB) that has been shown to protect against ankle
      injuries. METHODS: Male Army airborne students (N = 1677) completed a
      questionnaire after they had successfully executed 4 of the 5 jumps necessary for
      qualification as a military paratrooper. The questionnaire asked about injuries
      during parachute descents, demographics, lifestyle characteristics, physical
      characteristics, physical fitness, airborne recycling (i.e., repeating airborne
      training because of failure to qualify on a previous attempt), PAB wear, problems
      with aircraft exits, and injuries in the year before airborne school. A final
      section of the questionnaire solicited open-ended comments about the PAB.
      RESULTS: Increased risk of a parachute-related injury occurred among students who
      had longer time in service, were older, taller, heavier, performed fewer push
      ups, ran slower, were airborne recycles, did not wear the PAB, had an aircraft
      exit problem, and/or reported an injury in the year prior to jump school. Among
      students who wore the brace, most negative comments about the PAB had to do with
      design, comfort, and difficulties during parachute landing falls. CONCLUSIONS:
      This study supported some previously identified injury risk factors (older age,
      greater body weight, and not using a PAB) and identified a number of new risk
      factors. To address PAB design and comfort issues, a strap is being added over
      the dorsum of the foot to better hold the PAB in place.

PMID- 18619130
TI  - Seasonal levels of melatonin, thyroid hormones, mood, and cognition near the
      Arctic Circle.
AB  - INTRODUCTION: The associations between melatonin and thyroid hormones and changes
      in mood and cognitive performance caused by exposure to cold and darkness were
      examined in 12 circumpolar residents during winter and summer. METHODS: Each
      participant was exposed to three different experimental conditions in random
      order: 1) 22 degrees C and bright light; 2) 10 degrees C and bright light; and 3)
      10 degrees C and dim light. The duration of each exposure was 24 h. RESULTS:
      Increased serum melatonin and thyrotropin were associated with decreased rectal
      temperature (r = -0.446 - -0.580) and increased mean skin temperature (r = 0.204
      0.519). Higher serum melatonin was associated with increased vigor (r = 0.330)
      and decreased accuracy on simple cognitive tasks (r = -0.332 - -0.430). Increased
      serum free triiodothyronine (fT3) was associated with decreased negative mood
      scores (r = -0.365 - -0.483), decreased response time (RT) on the simple reaction
      time (SRT) task (r = -0.606), and decreased accuracy on the addition/subtraction
      task (r = -0.372). Higher serum free thyroxine was associated with decreased
      fatigue and anger (r = -0.409 - -0.522). Increased serum thyrotropin was
      associated with decreased accuracy and RT on the SRT task and decreased RT on the
      grammatical reasoning task (r = -0.315 - -0.415). CONCLUSIONS: Associations
      between serum melatonin and thyroid hormones with mood were consistent with the
      psychological changes associated with the polar triiodothyronine syndrome. Also,
      serum melatonin and thyrotropin were associated with impaired and fT3 with
      improved cognitive performance, supporting the decrements in cognitive
      performance associated with the polar triiodothyronine syndrome.

PMID- 18619131
TI  - Cerebral metabolism during air transport of patients after surgery for malignant
      glioma.
AB  - INTRODUCTION: Post-operative air transport of patients following an intracranial
      procedure is not uncommon. The transport itself may pose a risk, and if there are
      harmful effects to the brain this should be reflected in the brain metabolism.
      The aim of this study was to analyze possible alterations in cerebral metabolism
      that could be caused by air transport. METHODS: Four patients with glioblastomas
      were operated with a biopsy or a craniotomy. During this procedure microdialysis
      catheters were placed in tumor tissue or brain adjacent to tumor and in normal
      cerebral tissue. In this study we have analyzed cerebral glucose metabolites
      (glucose, lactate / pyruvate ratio), glycerol, and glutamate at five time points
      during a 24-h period including air transport. RESULTS: Analyzing mean values,
      there was a small but significant increase in the lactate/pyruvate ratio from
      45.18 to 47.78 in normal cerebral tissue after air transport compared to a
      previous fasting sample. For tumor tissue there was a small decrease in glucose
      from 1.04 to 0.92 mmol L(-1) and an increase in glutamate from 13.08 to 19.06
      micromol L(-1). There were no other significant differences in the analyzed
      cerebral metabolites after air transport. DISCUSSION: There were only minor
      differences in levels of cerebral metabolites after air transport compared to a
      previous fasting sample. Thus it seems that air transportation of the four
      reported patients did not cause any major cellular damage or metabolic changes as
      assessed by extracellular glucose, lactate/pyruvate ratio, glycerol, or
      glutamate.

PMID- 18619132
TI  - Spontaneous pneumothorax in flight as first manifestation of alpha-1 antitrypsin
      deficiency.
AB  - Alpha-1 antitrypsin deficiency is a genetic condition that increases the risk of
      a variety of conditions including pulmonary emphysema and chronic liver disease.
      We report on a 33-yr-old male fighter pilot with early-onset pulmonary emphysema
      with bullae who developed spontaneous pneumothorax during in-flight combat
      training. A CT scan of his chest after removal of the chest tube showed multiple
      variably sized bullae and pulmonary cysts scattered throughout both lungs. Serum
      levels of alpha-1 antitrypsin were markedly decreased. Genetic analyses showed a
      PI ZZ genotype. Alpha-1 antitrypsin deficiency often goes undiagnosed by flight
      surgeons, which is a risk to flight safety.

PMID- 18619133
TI  - Medullary sponge kidney and urinary calculi: aeromedical concerns.
AB  - Medullary sponge kidney (MSK) is a benign disorder associated with a lifetime
      risk of renal stones in 60% of patients. Patients frequently have episodic
      painless hematuria, but are often otherwise asymptomatic unless renal calculi or
      infections complicate the disease. Nephrolithiasis is a relative, but frequently
      enforced, contraindication to space or other high-performance flight. Two case
      reports of asymptomatic NASA flight crew with MSK and three cases of United
      States Air Force (USAF) military aviators diagnosed with MSK are reviewed. All
      cases resulted in waiver and return to flight status after treatment and a
      vigorous followup and prophylaxis protocol. MSK in aviation and spaceflight
      necessitates case-by-case evaluation and treatment to rule out other potential
      confounding factors that might also contribute to stone formation and in order to
      requalify the aviator for flight duties.

PMID- 18619134
TI  - On the practicality of emergency surgery during long-duration space missions.
AB  - While discussions of the practicality of surgery in space often focus on
      technical issues, such as adapting instrumentation and procedures for use in
      microgravity, programmatic issues need to be addressed if meaningful capabilities
      for emergency surgery are to be considered for human exploration missions beyond
      low Earth orbit. Advanced technologies that have been evaluated, including
      simulation-enhanced training, telementoring, or robotic assistance, might help
      prepare or augment a crew medical officer, but a physician with advanced training
      and relevant experience will be needed if surgical capabilities beyond basic
      emergency aid are to be considered. Specific operational roles for physician
      astronauts should be established.

PMID- 18619135
TI  - This month in aerospace medicine history--July 2008.

PMID- 18619137
TI  - Space medicine at the NASA-JSC, neutral buoyancy laboratory.

PMID- 18619136
TI  - Chamber advances for delivery of hyperbaric oxygen therapy.
AB  - In this edition of the Watch, Dr. Robins has provided a review of hyperbaric
      chamber therapy, with particular discussion of new monoplace chambers and their
      expanded role in emergency medicine.

PMID- 18619138
TI  - [Oral erythroplakia and erythroleukoplakia: red and red-white dysplastic lesions
      of the oral mucosa--part 2: cytodiagnosis, pathogenesis, therapy, and prognostic
      aspects].
AB  - The second part of the present review article presents and discusses the current
      literature regarding cytodiagnostic aspects, pathogenesis, therapy, incidence of
      recurrence, and malignant transformation rate of oral erythroplakia (OE) and oral
      erythroleukoplakia (OEL). Oral cytopathology, eventually in combination with DNA
      cytometry, can add valuable information to conventional histopathology, but is
      not able yet to replace the aforementioned. Numerous molecular genetic variants
      have been studied in precancerous lesions to gain knowledge about the prognosis
      of these lesions. Still, there are no evidence-based parameters available to
      safely detect precursor lesions that will undergo malignant transformation in the
      future. Excision of OE and OEL should be performed with a margin of safety using
      the CO2 laser or a scalpel. Data about incidence of recurrence and malignant
      tranformation rates of OE are mostly based upon case reports or case series. The
      OEL has a significantly higher risk of malignant transformation than oral
      leukoplakias.

PMID- 18619139
TI  - [Effects of tobacco use on systemic health: relevant information for dentistry
      (II)--part 2: cardiovascular diseases and public health issues].
AB  - This is the sixth and concluding part of a series of publications from the Swiss
      task force named "Smoking - Intervention in the private dental office" on the
      topic "tobacco use and dental medicine". The focus of this review is the effects
      of smoking for the development of atherosclerosis as pathohistological correlate
      for acute coronary syndrome (ACS), arterial occlusive disease, and
      cerebrovascular diseases (stroke). Additionally, a causal relationship between
      tobacco use and an increased rate for complications during pregnancy and child
      birth will be discussed. Next to causal therapy of local and systemic diseases in
      general, an emphasis must be given to tobacco use prevention and cessation.
      Finally, important public health issues concerning smoking and tobacco use will
      be demonstrated, and options to improve the current situation will be presented.

PMID- 18619140
TI  - [The bronze head of Seuthes III. A maxillofacial surgery case from antiquity].
AB  - The authors had the opportunity to visit the tumulus of Golijama Kosmatka in
      todays central Bulgaria and the there found burial artefacts of Seuthes III., a
      Thracian King who lived in the 4th-3rd century BC. The beautiful bronze head of
      the king found in front of the burial site shows the typical sequelae of a
      dislocated lateral mid face fracture in all details. These findings do fit and
      also confirm the troublesome times this local king went through after the death
      of Alexander the Great.

PMID- 18619141
TI  - Effects of several surfactants and high-molecular-weight organic compounds on
      decomposition of trichloroethylene with zerovalent iron powder.
AB  - We investigated the effects of coexisting surfactants and high-molecular-weight
      organic compounds on the reductive dechlorination of trichloroethylene by
      zerovalent iron powder to determine whether these additives had utility as
      washing reagents for remediation of soil and groundwater pollution. During the
      dechlorination reaction, the amount of trichloroethylene decreased, and the
      formation of cis-1,2-dichloroethylene was observed. The decomposition of
      trichloroethylene was found to be first-order with respect to the
      trichloroethylene and zerovalent iron concentrations when the solution contained
      no additives. The rates of decomposition of trichloroethylene in the presence of
      the additives were lower than the rate in the absence of the additives: the rate
      constant was reduced by a factor of 0.7 for the cationic surfactant
      cetyltrimethylammonium bromide; by a factor of 0.5 for the anionic surfactants
      sodium n-dodecylbenzenesulfonate, sodium n-dodecylsulfate, and sodium n
      dodecanesulfonate and for the high-molecular-weight organic compounds soluble
      starch, beta-cyclodextrin, and polyethyleneglycol 6000; and by a factor of 0.2
      for sodium laurate and the nonionic surfactants Triton X-100, Tween 20, Tween 60,
      Brij 35, and Brij 58. Comparison of the concentrations of the nonionic
      surfactants with their critical micellar concentrations indicated that the rate
      reducing effect of these additives was due to solubilization of trichloroethylene
      into the micellar phase. The adsorption of trichloroethylene onto the zerovalent
      iron surface was also affected by the presence of the additives. Thus, our
      results indicated that the changes in the decomposition rate of trichloroethylene
      were determined by several factors.

PMID- 18619142
TI  - Effects of limestone on the dissolution of phosphate from sediments under
      anaerobic condition.
AB  - This paper describes a study on the role of limestone on the dissolution of
      phosphates when phosphate-containing sediments are put under anaerobic
      conditions. Anaerobic decomposition of organic substances produces both organic
      acids and carbonic acids which in turn could accelerate the dissolution of the
      phosphates. If limestone coexisted, both phosphate and limestone would compete as
      receptors of hydrogen ions so as to affect the dissolution of phosphate. A small
      quantity of calcium hydroxyapatite, alone or mixed with limestone powder, was put
      in contact with an aqueous solution of acetic acid or carbonic acid and the
      variations in phosphate concentration were determined over time. The results
      showed that the phosphate concentration was remarkably low in the case of
      limestone presence, in comparison with the case of limestone absence. This
      signifies that the coexistence of limestone suppresses the dissolution of
      phosphate by organic acid and/or carbonic acid. Separate experiments conducted by
      developing an anaerobic condition, after mixing lake sediments with dried leaves
      and limestone, allowed us to observe that the existence of limestone suppressed
      the dissolution of phosphate. It seems that the limestone acts as a material
      sacrificing to the leaching of hydrogen ions from the acids produced under
      anaerobic conditions. These results show that the application of limestone might
      be a useful measure to prevent deterioration of water quality through
      eutrophication, by breaking the internal loading of phosphates in eutrophic water
      bodies.

PMID- 18619143
TI  - Complete dechlorination of tetrachloroethylene by use of an anaerobic Clostridium
      bifermentans DPH-1 and zero-valent iron.
AB  - A laboratory test was conducted to examine the combined effect of an anaerobic
      Clostridium bifermentans DPH-1 and addition of zero-valent iron (Fe0) on the
      reductive dechlorination of tetrachloroethylene (PCE). In addition, the
      dechlorination of cis-1,2-dichloroethylene (cDCE) produced from PCE was examined
      using Fe0. The cDCE produced was completely dechlorinated to non-toxic end
      products, mostly, ethylene by a subsequent chemical reductive process. Production
      of ethylene was dramatically increased with increase of initial cDCE
      concentration in the range of 10.3 microM to 928 microM (1.0-90 mg l(-1)) and the
      velocity constant was calculated to be 0.38 day(-1). On the other hand, the
      combined use of strain DPH-1 and Fe0 showed the most significant effect on the
      initial PCE dechlorination, but cohesion of Fe0 was found to inhibit the
      dechlorination rate of PCE. It is thought that phosphoric acid iron contained in
      a medium forms film on the surface of iron particle, so oxidation of iron is
      inhibited.

PMID- 18619144
TI  - Removal of heavy metals from oil sludge using ion exchange textiles.
AB  - Development of a new simple and economic method for heavy-metal removal from oil
      sludge using ion exchange textiles was the main objective of this research. Three
      experimental stages were developed for this purpose using the bottom tank oil
      sludge from the Shell Canada refinery in Montreal, Canada. The first stage
      consisted of the direct application of ion exchange to oil sludge. The second
      stage included the pretreatment of oil sludge with organic solvents prior to the
      application of ion exchange process. The third stage included the pretreatment of
      oil sludge with an aqueous solution in order to extract heavy metals to the
      aqueous phase and then apply ion exchange textiles to the aqueous phase. Best
      results were obtained when acetone was used as an organic solvent leading to a
      total removal of vanadium while cadmium, zinc, nickel, iron, copper by 99%; 96%;
      94%; 92% and 89%, respectively.

PMID- 18619145
TI  - Arsenate sorption by hydrous ferric oxide incorporated onto granular activated
      carbon with phenol formaldehyde resins coating.
AB  - A simple and effective method was developed using phenol formaldehyde (PF) resins
      to immobilize hydrous ferric oxide (HFO) onto granular activated carbon (GAC).
      The resulting sorbent possesses advantages for both the ferric oxide and the GAC,
      such as a great As-affinity of ferric oxide, large surface area of GAC, and
      enhanced physical strength. The studies showed that within one hour this sorbent
      was able to remove 85% of As(V) from water containing an initial As(V)
      concentration of 1.74 mg l(-1). The As(V) adsorption onto the sorbent was found
      to follow a pseudo-second order kinetics model. The adsorption isotherms were
      interpreted in terms of the Langmuir and Freundlich models. The equilibrium data
      fitted very well to both models. Column tests showed that this sorbent was able
      to achieve residual concentrations of As(V) in a range of 0.1-2.0 microg l(-1)
      while continuously treating about 180 bed volume (BV, 130 ml-BV) of arsenate
      water with an initial As(V) concentration of 1886 microg l(-1) at a filtration
      rate of 13.5 ml min(-1), i.e., an empty bed contact time (EBCT) of 9.6 min and a
      gram sorbent contact time (GSCT) of 0.15 min. After passing 635 BV of arsenate
      water, the exhausted sorbent was then tested by the Toxicity Characteristic
      Leaching Procedure (TCLP, US EPA Method 1311) test, and classified as non
      hazardous for disposal. Hence, this HFO-PF-coated GAC has the capability to
      remove As(V) from industrial wastewater containing As(V) levels of about 2 mg l(
      1).

PMID- 18619146
TI  - Effects of shock 2,4-dichlorophenol (DCP) and cod loading rates on the removal of
      2,4-DCP in a sequential upflow anaerobic sludge blanket/aerobic completely
      stirred tank reactor system.
AB  - The treatability of 2,4-dwichlorophenol (DCP) was studied in an anaerobic/aerobic
      sequential reactor system. Laboratory scale upflow anaerobic sludge blanket
      (UASB) reactor/completely stirred tank reactors (CSTR) were operated at constant
      2,4-DCP concentrations, and increasing chemical oxygen demand (COD) loading
      rates. The effect of shock organic loading rates on 2,4-DCP, COD removal
      efficiencies and methane gas production were investigated in the UASB reactor.
      When the organic loading rate was increased from 3.6 g l(-1) d(-1) to 30.16 g l(
      1) d(-1), the COD and 2,4-DCP removal efficiencies decreased from 80 to 25% and
      from 99 to 60% in the UASB reactor. The optimum organic loading rates for maximum
      2,4-DCP (E=99-100%) and COD (E=65-85%) removal efficiencies were 25-30 and 8-20 g
      COD l(-1) d(-1), respectively. The percentage of methane of the total gas varied
      between 70 and 80 while the organic loadings were 18 g-COD l(-1) d(-1) and 20.36
      g-COD l(-1) d(-1), respectively. During 80 days of operation, 2,4-DCP
      concentration was found to be below 0.5 and 0.1 mg l(-1) in aerobic reactor
      effluent resulting in 78 and 100% removal efficiencies. When the hydraulic
      retention time (HRT) was 18.72 h, the 2,4-DCP removal efficiency was 97% in the
      aerobic reactor. The optimum COD removal efficiency was 78.83% in anaerobic
      reactor effluent at an influent COD loading rate of 7.238 g-COD l(-1) d(-1) while
      83.6% maximum COD removal efficiency was obtained in the aerobic reactor,
      resulting in a total COD removal efficiency of 96.83% in the whole system. The
      2,4-DCP removal efficiency was 99% in the sequential anaerobic (UASB)/aerobic
      (CSTR) reactor system at COD loading rates varying between 11.46 and 30.16 g-COD
      l(-1) d(-1).

PMID- 18619147
TI  - Oxidation of nonionic surfactants by Fenton and H2O2/UV processes.
AB  - The oxidation of 10 nonionic surfactants (6 alcohol ethoxylates and 4 alkylphenol
      ethoxylates) by Fenton and H2O2/UV processes was investigated in synthetic
      (deionized water) and real aqueous matrices, i.e. secondary effluent from
      municipal wastewater treatment plant and groundwater. Batch tests were carried
      out to assess the optimal dosages of reagents leading to the total removal of
      surfactants. Regardless to the specific surfactant, both Fenton and H2O2/UV
      treatments of synthetic solutions containing one single surfactant (C0=14 mg l(
      1)) always caused its rapid and quantitative removal (96-99%) with a
      corresponding very low (0-18%) TOC decrease. Only for the Fenton treatment,
      linear relationships were found between the amounts of H2O2 and Fe2+ necessary
      for surfactant removal and the ethoxy chain length of each surfactant.
      Conversely, in the case of H2O2/UV treatment the H2O2 dosage causing the
      quantitative oxidation of the treated surfactant depended on the length of both
      chains: the ethoxy and the hydrophobic one. Mixtures of the 10 surfactants (1.4
      mg l(-1) each) were treated in both synthetic and real matrices. These latter
      were different in the case of Fenton (i.e. municipal secondary effluent) or
      H2O2/UV (i.e. real groundwater) treatments. Fenton treatment of municipal
      secondary effluent containing the surfactants mixture led to its total removal
      when a molar ratio [Total surfactants]/[H2O2]/[Fe2+] equal to 1/17/12 was used.
      As for H2O2/UV treatment of real groundwater samples, quantitative removal of
      surfactants mixture was achieved with a molar ratio [Total surfactants]/[H2O2]
      equal to 1/7.4. Surfactants mixture removals, if compared in deionized water and
      in real matrices, showed the same matrix effect during both treatments, i.e. less
      amounts of reagents were always required in synthetic solutions.

PMID- 18619148
TI  - Use of synchronous fluorescence spectra to estimate biochemical oxygen demand
      (BOD) of urban rivers affected by treated sewage.
AB  - Synchronous fluorescence spectra and the first derivative spectra of urban rivers
      affected by treated sewage were studied to find the optimum index for biochemical
      oxygen demand (BOD) estimation. In addition, various sample treatment methods as
      well as the multiple regression method using available monitoring parameters were
      examined to improve the BOD estimation capability of the indices. From July to
      November 2006, grab samples were collected from three rivers in the city of
      Seoul, Korea, which included one receiving effluent from a municipal wastewater
      treatment facility. The BOD values of the samples ranged from 0.4 to 28.0 mg l(
      1). Out of the many fluorescence characteristics observed, the relative
      fluorescence intensity at 283 nm to 245 nm from the synchronous spectra was
      selected as the optimum fluorescence estimation index because it had the highest
      positive correlations with the BOD values (r = 0.910). The filtration process,
      using GF/F filter prior to the fluorescence measurement, resulted in an enhanced
      correlation demonstrating that the removal of suspended solids from the samples
      helps alleviate, to some extent, the interference of light scattering. In
      contrast, the same correlation was not enhanced by the pH adjustment of the
      sample to minimize the complexation of organic matter with cations. The multiple
      regression method, using either light scattering intensity at 633nm or turbidity,
      greatly enhanced the correlation between measured and predicted BOD values. The
      correlation was even higher than that obtained for filtered samples, thus
      suggesting that the multiple regression method based on the original sample is
      more effective than sample treatment in enhancing BOD estimation.

PMID- 18619149
TI  - SO2 removal with ferric sulfate solution.
AB  - The determination of the influence of the concentration of ferric sulfate
      solution on SO2 absorption was performed in this study. It was found that the SO2
      absorption efficiency increased with increasing ferric concentration, and
      decreased with the acidity of the spraying solution. As the hydrolysis of ferric
      ions occurs in solution, the SO2 removal efficiency increased slowly with
      increasing Fe(III) concentration. Taking into account the hydrodynamic and mass
      transfer characteristics of the packed column, the enhancement factor (E) was
      found to depend on the concentration of the ferric ions and pH, which indicated
      that it could be used for the simulation or design of SO2 scrubbers.

PMID- 18619150
TI  - Recovery of valuable soluble compounds from washing waters generated during small
      fatty pelagic surimi processing by membrane processes.
AB  - This work focuses on the treatment of washing waters coming from surimi
      manufacturing using ultrafiltration technology at a laboratory scale. Four
      membrane materials (poly-ether sulfone, polyacrilonytrile, poly vinylidene
      fluoride and regenerated cellulose) and 5 Molecular Weight Cut-Off (from 3 to 100
      kDa) have been studied at bench laboratory scale using the pilot Rayflow 100,
      commercialised by Rhodia Orelis. The investigation deals with the ability for
      membranes to offer a high retention of biochemical compounds (proteins and
      lipids). Results obtained during adsorption tests showed that the regenerated
      cellulose material seems to be the most appropriate with regards to pore size
      reduction due to the protein-adsorption. During the ultrafiltration of the
      washing water, the regenerated cellulose material leads to the best results,
      followed by the polyacrylonitrile and poly-vinylidene fluoride materials. Poor
      results were obtained with polyether sulfone membrane. Compared to the other
      materials, the regenerated cellulose is the easiest to regenerate, with minimal
      cleaning water and no chemical treatment necessary. Biochemical characterization
      of the fractions generated during the ultrafiltration with the polyacrilonytrile,
      poly vinylidene fluoride and regenerated cellulose membranes showed that all the
      membranes provided a high recovery rate of the lipids and proteins. The 10 kDa
      regenerated cellulose membrane had the highest performance and was further
      evaluated. With such a treatment, the chemical oxygen demand was reduced by 75%.
      By performing hydrolysis followed by a centrifugation, biochemical composition of
      the sludge and liquid fraction were modified, producing an insoluble fraction
      containing fats and few proteins and a soluble fraction containing proteins and
      few fats. The sludge, initially insoluble, was mainly solubilized during
      hydrolysis, and lipids and peptides were concentrated by ultrafiltration.

PMID- 18619151
TI  - Bacterial community dynamics and conversion of inorganic nitrogen under aerobic
      and micro-aerobic conditions.
AB  - To investigate the inorganic nitrogen conversion in reactors that were operated
      under aerobic and micro-aerobic conditions and to identify populations that
      became acclimated in the reactors under those oxygen conditions, we operated two
      reactors with 72 h of hydraulic retention time and an artificial medium
      containing ammonium- and nitrite-nitrogen without any organic compound. We
      determined the concentration of inorganic nitrogen in samples from the reactors
      and the microbial community structure in the reactors by using PCR-DGGE of the
      partial 16S rRNA gene. The results showed that nitrification to nitrate fully
      progressed in the aerobic reactor within 24 h, but we could not find any obvious
      reaction in the micro-aerobic reactor. In a view of microbial community
      structure, the total number of microorganisms composing the communities in the
      reactors was dramatically decreased compared to those of the initial inoculated
      sludge that originated from the Jang-lim sewage treatment plant in Busan,
      Republic of Korea because of the limited nutrients present. One Nitrospira sp.
      was clearly detected under both aerobic (as DO > 2 mg l(-1)) and micro-aerobic
      (as DO < 0.7 mg l(-1)) conditions while no AOB-like bacterium was exactly matched
      among main bands. By the results, nitrite-oxidizing bacteria may be more tolerant
      to variations in oxygen, or the occupation of ammonia-oxidizing bacteria as
      dominant groups may have been inhibited by substrate starvation and high
      concentrations of nitrite-N in influent.

PMID- 18619152
TI  - Copper release in low and high alkaline water.
AB  - Copper release in drinking water, caused by electrochemical corrosion of
      household distribution systems, was investigated. Experiments were developed
      testing both low and high alkaline water in stagnant conditions. The effect of
      varying stagnation time was investigated also. Both soluble and insoluble copper
      compounds, produced by corrosion processes are quantified, using appropriate
      experimental procedures. On the basis of obtained results, copper concentration
      in stagnant water is defined as a function of water alkalinity, while total metal
      release is defined as a function of stagnation length, and is not dependent on
      water alkalinity.

PMID- 18619153
TI  - [Treatment of PAH-contaminated aluminium wastes by flotation using amphoteric
      surfactants].
AB  - The aluminium industry produces wastes polluted with polycyclic aromatic
      hydrocarbons (PAH). The most important PAH found in these wastes is
      benzo(b,j,k)fluoranthene (BJK) at concentrations exceeding the permitted levels
      (>1000 mg kg(-1)). The objective of this research was to compare the performances
      of amphoteric (BW and CAS) and non-ionic surfactants (Triton X-100 and Tween 80),
      at a concentration of 0.5% (w w(-1)), for PAH removal (and particularly for BJK)
      during washing treatment of aluminium industry wastes. The best removal yield of
      BJK (35%) has been measured during treatment with CAS. The efficiency of this
      surfactant has been further improved by using a flotation process. Flotation
      tests have also been realized at different CAS concentrations (0.1, 0.2, 0.25 and
      0.5% w w(-1)) and using different total solids (7, 10, 15 and 20% w v(-1)). The
      highest BJK removal yield (68%) has been obtained using 0.5% CAS and a total
      solids concentration of 15%. The rate of hazardous wastes produced in these
      conditions represents 10% of the initial weight of aluminium wastes treated.

PMID- 18619154
TI  - The combat casualty care special edition.

PMID- 18619155
TI  - Benchmarking the UK military deployed trauma system.

PMID- 18619156
TI  - Trauma governance in the UK defence medical services.

PMID- 18619157
TI  - The operational emergency department attendance register (OPEDAR): a new
      epidemiological tool.
AB  - AIM: To determine the number, status and nature of emergency department
      attendances to deployed field hospitals. POPULATION: All attendances to the
      emergency department (ED) of deployed field hospitals in support of Operation
      TELIC (Iraq) from initial entry war fighting to enduring operations. METHODS:
      Analysis of hand written and electronic registers ED attendance registers and
      validation with four other data sources. RESULTS: Validation of data held on
      OpEDAR against 4 other data sources shows that OpEDAR is accurate, but that
      accuracy can be further improved. 26,746 ED attendances recorded on OP TELIC from
      19 March 2003 to 11 November 2006. 21,112 (78.9%) were UK military. Overall,
      43.5% were admitted from ED. Attendances peaked during TELIC phases 2 (422.9 per
      1,000 troops deployed), but have settled to around 200 per 1,000 troops deployed
      in the more recent phases. Ophthalmology rates peaked in TELIC 2 to 20.72 per
      1,000 and have since reduced to a consistent 10 to 15 per 1,000. This suggests
      that preventative measures introduced for eye injury are incompletely effective
      or incompletely utilised. CONCLUSIONS: OpEDAR is a clinical tool to inform
      manning, equipment and training requirements for enduring and new operations,
      focused on the requirements of the emergency department. Multivariate quality
      control models applied in industry could be applied to OpEDAR to produce a
      dynamic epidemiological tool that identifies emerging case clusters and
      facilitates deployed commanders to take preventative action.

PMID- 18619158
TI  - Operational mortality of UK service personnel in Iraq and Afghanistan: a one year
      analysis 2006-7.

PMID- 18619159
TI  - Operational morbidity analysis of soft tissue injuries during Operation TELIC.
AB  - Soft tissue injury accounted for one in five of all presentations to the
      Emergency Department (ED) during Operation TELIC (UK forces in Iraq) from March
      2003 to November 2006. This ranks soft tissue complaints as the most frequent
      cause of attendance to a deployed field hospital ED. This paper analyses the
      injury patterns, together with implications for future clinical practice and
      operational planning to prevent injury, optimise patient care and maximize force
      regeneration.

PMID- 18619160
TI  - Combat "Category A" calls: evaluating the prehospital timelines in a military
      trauma system.
AB  - AIM: To establish the pre-hospital timelines for seriously injured UK military
      casualties on OP HERRICK. POPULATION: All consecutive MERT and MERT-E
      mobilizations from Camp Bastion, Helmand Province, between 04 May 06 and 18 Jun
      07. METHODS: Interrogation of MS Access database compiled from paper patient
      report forms for each casualty transported. RESULTS: 528 patients were
      transported. 84.6% (456) were battle casualties. There were 192 GSW and 233
      casualties with blast/fragmentation injuries. 189 of 528 (35.7%) were UK Service
      personnel. Median time from injury to handover at the emergency department for UK
      military T1 casualty subset was 99 minutes. CONCLUSION: The public perception of
      excessive timelines for pre-hospital care in Afghanistan has been distorted. The
      ground truth is a pre-hospital time less than one quarter of the cited 7 hours
      for the seriously injured subset of UK Service personnel.

PMID- 18619161
TI  - Determining the composition and benefit of the pre-hospital medical response team
      in the conflict setting.
AB  - AIM: To determine the optimal composition o f the pre-hospital medical response
      team (MERT) and the value of pre-hospital critical care interventions in a
      military setting, and specifically to determine both the benefit of including a
      doctor in the pre-hospital response team and the relevance of the time and
      distance to definitive care. METHOD: A comprehensive review of the literature
      incorporating a range of electronic search engines and hand searches of key
      journals. RESULTS: There was no level 1 evidence on which to base conclusions.
      The 15 most relevant articles were analysed in detail. There was one randomized
      controlled trial (level 2 evidence) that supports the inclusion of a doctor on
      MERT. Several cohort studies were identified that analysed the benefits of
      specific critical care interventions in the pre-hospital setting. CONCLUSIONS: A
      doctor with critical care skills deployed on the MERT is associated with improved
      survival in victims of major trauma. Specific critical care interventions
      including emergency endotracheal intubation and ventilation, and intercostal
      drainage are associated with improved survival and functional recovery in certain
      patients. These benefits appear to be more easily demonstrated for the rural and
      remote setting than for the urban setting.

PMID- 18619162
TI  - Casualty evacuation timelines: an evidence-based review.
AB  - There is no tri-modal death distribution demonstrable in modern military
      conflict. Recent UK, Palestinian and Israeli data suggests that nine out of every
      ten injured soldiers that die do so within minutes of wounding from insurvivable,
      unsalvagable trauma. Having the surgeon on the battlefield with the soldier has
      been shown to make no difference to these survival rates. Early definitive airway
      control using rapid sequence induction and intubation is of benefit to the head
      and airway injured. Once this airway is secured, these early survivors may be
      transported for up to 2 hours receiving intensive care level treatment:
      Hypotensive resuscitation with blood transfusion, administration of adjunctive
      clotting factors, hypothermia mitigation, administration of antibiotics,
      analgesics, novel haemostatics, splintage, FAST scanning can all be performed in
      flight. The second peak of death comes from truncal bleeding and CNS injury.
      Those with truncal (or junctional) bleeding require significant surgical,
      logistic and haemostatic support. Those with CNS injury require CT scanning and
      specialized neurosurgical care. These subgroups do best in large well-resourced
      hospital units which have the infrastructure, blood, climate control, knowledge
      and staffing levels to deal with them. Stopping elsewhere en-route to these
      larger centres is of uncertain benefit. Our resources must be optimised to save
      the many that could be saved, rather than dispersed for the few who will not.
      Wounded soldiers need to be undergoing surgery in the operating theatres of these
      large centres within three hours of wounding.

PMID- 18619163
TI  - Lessons learnt from explosive attacks.

PMID- 18619164
TI  - Military intensive care part 1. A historical review.
AB  - ICU is a product of clinical developments, technological advances, social changes
      and history. Military ICU reflects all of these as well as deployed operational
      experience. Having considered how military ICU got to where it is, the next
      article will consider current practice.

PMID- 18619165
TI  - Military intensive care part 2. Current practice.

PMID- 18619166
TI  - Military intensive care part 3. Future directions.

PMID- 18619167
TI  - Damage control resuscitation.
AB  - Damage Control Resuscitation (DCR) is a novel concept that draws together a
      series of technical and organisational advances in combat casualty care. It is
      consistent with and encapsulates the established concept of damage control
      surgery (DCS).

PMID- 18619168
TI  - A proactive approach to the coagulopathy of trauma: the rationale and guidelines
      for treatment.

PMID- 18619169
TI  - UK defence medical services guidance for the use of recombinant factor VIIa
      (rFVIIa) in the deployed military setting.
AB  - Use of recombinant Factor VIIa (rFVIIa) for trauma is currently an 'off label'
      use. There are reports of rFVIIa contributing to the successful outcome of
      military trauma patients. This paper sets out the current position of the UK
      Defence Medical Services with regard to using rFVIIa in military trauma.

PMID- 18619170
TI  - Tourniquet use in combat trauma: UK military experience.
AB  - AIM: To determine the prevalence of tourniquet use in combat trauma, the
      contribution to lives saved and the complications of their use in this
      environment. POPULATION: All casualties treated at UK field hospital facilities
      in Iraq and Afghanistan and meeting criteria for entry into UK Joint Theatre
      Trauma Registry (JTTR) from 04 Feb 03 to 30 Sep 07. METHODS: Cases were
      identified from UK JTTR. Casualties from Permanent Joint Overseas Bases (PJOBs)
      were excluded. ISS, NISS, TRISS and ASCOT were calculated automatically within
      JTTR from AIS 2005 (Military) codes. RESULTS: 1375 patients met UK JTTR entry
      criteria for the period specified (excluding PJOBs). 70/1375 patients (5.1%) were
      treated with one or more tourniquets (total 107 tourniquet applications). 61/70
      (87%) survived their injuries. 17/70 (24%) patients had 2 or more tourniquets
      applied. 64/70 patients received a tourniquet after April 2006, when tourniquets
      were introduced as an individual first aid item. 43/70 (61%) patients were UK
      military. CONCLUSIONS: ISS and TRISS are poorly representative of injury severity
      and outcome for combat trauma involving isolated multiple limb injuries and
      cannot be used to discriminate whether a tourniquet is life-saving. The presence
      of severe isolated limb injuries, profound hypovolaemic shock and the requirement
      for massive transfusion reasonably identifies a cohort where the use of one or
      more tourniquets pre-hospital to control external bleeding can be said to be life
      saving.

PMID- 18619171
TI  - Intra-osseous access (EZ-IO) for resuscitation: UK military combat experience.
AB  - Military trauma produces predominantly blast and fragmentation injury, commonly
      resulting in haemorrhagic shock. Injury patterns to limbs are such that the
      conventional sites for venous cannulation may be unsuitable. The EZ-IO (Vidacare,
      San Antonio) system is one of a number of novel products designed for
      intraosseous (IO) access in adults or children. In three months of combat
      casualty care in Helmand Province, Afghanistan, the UK Defence Medical Services
      used EZ-IO for emergency vascular access on 26 patients (16 adults; 10 children).
      23/26 patients had IO access obtained in the emergency department; 3/26 had pre
      hospital IO access within a tactically flying helicopter. A total of 32 needles
      were inserted, with 97% effective function. IO needles were used to administer
      fluid (crystalloid, packed red cells and fresh frozen plasma) and drugs
      (analgesics, cardiac arrest drugs, antibiotics, drugs for both rapid sequence
      induction and maintenance of anaesthesia). No complication of infection was
      noted, but pain was observed in responsive patients with the pain of infusion
      exceeding that of the underlying injuries in 3 cases.

PMID- 18619173
TI  - Managing painful neuropathy in diabetes.

PMID- 18619172
TI  - Paediatric thoracic damage control resuscitation for ballistic injury: a case
      report.
AB  - This case is of an 8-year-old child who had a cardiac arrest and an Emergency
      Department thoracotomy (EDT) following a penetrating fragmentation injury to the
      chest. The management included damage control resuscitation, recombinant Factor
      VIIa and a successful emergency department thoracotomy.

PMID- 18619174
TI  - Venous leg ulcers: where does surgery fit in?

PMID- 18619175
TI  - The Androgen Excess Society guidelines on glucose intolerance in the polycystic
      ovary syndrome: what do they mean and what should we do?

PMID- 18619176
TI  - Self-monitoring of blood glucose and treatment outcomes in type 2 diabetic
      patients.
AB  - OBJECTIVES: The aim of the study was to evaluate an association between the
      frequency of blood glucose self-monitoring (SMBG) and glycemic control assessed
      by glycated hemoglobin (HbA1C) levels. PATIENTS AND METHODS: A group of 600 type
      2 diabetic patients aged 63.4 +/- 9 years (32 to 85 years) and with a mean
      diabetes duration of 11.4 +/- 7.7 years (min. 1 year, max. 38 years) were asked
      to perform weekly blood glucose self-monitoring with an 8-point glucose profile
      on a chosen day. They were also asked to declare their self-monitoring frequency.
      HbA1C levels were measured in all the patients. RESULTS: Most of the patients
      reported that they performed their SMBG 1-2 times a day (44.3%) or 1-2 times a
      week (31.8%). All of them measured their blood glucose after an overnight fast
      and after breakfast. Most patients performed their measurements also after lunch
      and dinner. Less than 50% of patients did their measurements at night-time. The
      mean HbA1C level was 7.45 +/- 1.08%. Only 20% of patients achieved metabolic
      control of diabetes recommended by the Polish Diabetic Society (HbA1C < 6.5%). No
      severe hypoglycemia episodes were obsered. Glycated hemoglobin levels did not
      differ between the SMBG frequency groups. There was no correlation between HbA1C
      levels and the frequency of self-monitoring in any group. CONCLUSIONS: There was
      no correlation between the frequency of SMBG and HbA1C, which questions the need
      for multiple daily measurements of blood glucose in all type 2 diabetic patients.

PMID- 18619177
TI  - Serum insulin levels in patients with colorectal cancer.
AB  - INTRODUCTION: Insulin regulates metabolic processes and is an important growth
      factor, which is able to stimulate cell proliferation and transformation and to
      inhibit apoptosis. OBJECTIVES: The aim of the study was to analyze the fasting
      serum insulin level in patients with colorectal cancer in relation to the
      clinical stage of the disease, patients' overweight and obesity, and the
      localization of a tumor (in the colon and rectum). PATIENTS AND METHODS: Seventy
      patients with colorectal cancer, including 41 men and 29 women (at an average age
      of 65 years) were enrolled into the study. Patients with diabetes, other forms of
      cancer, or used hormones were excluded from the study. Medical records of the
      patients was evaluated. Glucose and insulin levels in blood serum were analyzed.
      All the patients were divided into groups according to the body mass index (BMI),
      the clinical stage of the disease (including TNM) and tumor localization.
      RESULTS: Ten patients (14.29%) were obese, 31 patients (44.29%) were overweight,
      and 29 patients had normal weight (41.43%). The average BMI was 25.98 +/- 5.38
      kg/m2. The mean glucose serum level was 5.49 +/- 1.0 mmol/l and the mean insulin
      serum level was 18.93 +/- 14.67 microlU/ml. There were no significant differences
      in glucose and insulin levels in relation to the stage of the disease, tumor
      localization and BMI. CONCLUSIONS: Overweight and obesity were observed in most
      of the colorectal cancer patients. No statistical associations were observed
      between serum insulin levels and tumor localization.

PMID- 18619179
TI  - Antiplatelet treatment of cardiovascular disease: a translational research
      perspective.
AB  - Platelet mediated thrombosis is the primary cause of ischemic event occurrence in
      patients with cardiovascular disease. The P2Y12 receptor plays a central role in
      thrombus generation and is therefore a major target for pharmacologic therapy.
      Although various clinical trials have demonstrated the efficacy of dual
      antiplatelet therapy with aspirin and clopidogrel, recurrent ischemic events
      occur in approximately 10% of patients with acute coronary artery syndromes.
      Recent translational research studies have explored the various limitations of
      dual antiplatelet therapy including wide response variability and resistance. The
      association of ischemic event occurrence with high on-treatment platelet
      reactivity to adenosine diphosphate has been reported in recent small studies
      suggesting that the latter may be a quantifiable and modifiable risk factor.
      Recent studies have identified a potential therapeutic target for P2Y12
      inhibitors that may influence the future development of personalized antiplatelet
      treatment strategies aimed at the reduction of ischemic event occurrence in high
      risk patients. Finally, based on the current evidence platelet reactivity may
      become a standard of care risk factor measured in all patients with
      cardiovascular disease.

PMID- 18619178
TI  - Long-term prognosis and risk factors for cardiac adverse events in patients with
      chronic systolic heart failure due to hypertension.
AB  - OBJECTIVES: The long-term prognosis and predictors of adverse cardiac events in
      hypertension-related chronic systolic heart failure (CHF) remain uncertain.
      Therefore, we sought to determine the major adverse cardiac events (MACE) in this
      group of patients. PATIENTS AND METHODS: One hundred and thirty two patients (83%
      males, age 48.6 +/- 8.2 years) in NYHA class II and III with hypertension-related
      chronic CHF were prospectively evaluated for three years. Hypertension was
      defined as blood pressure > or = 140/90 mmHg documented clinically twice for at
      least 5 years before the onset of CHF symptoms. All patients underwent coronary
      angiography to exclude coronary artery disease as a cause of CHF. Analysis of
      predictors of MACE (death, urgent heart transplantation and re-admission to the
      hospital due to CHF progression) during the 3 years of follow up was performed.
      RESULTS: After follow up the frequency of MACE was 41.7%. The independent
      predictors of MACE occurrence were as follows: the symptoms of depression [hazard
      ratio (HR) 2.58 (95% CI 1.44-4.63, p < 0.01)], end-diastolic diameter of the
      right ventricular (EDDRV) [HR 1.07 (95% CI 1.02-1.12, p < 0.01)] and D-dimers [HR
      2.24 (95% CI 1.08-4.67, p < 0.05)]. To define optimal prognostic accuracy of
      EDDRV and D-dimers the receiver operating characteristics curve analysis was
      performed. The cut-off for EDDRV was 28 mm (sensitivity 50%, specificity 67.6%,
      area under curve [AUC] 0.64, p < 0.01) and for D-dimers 0.23 microg/ml,
      (sensitivity 58%, specificity 64.2%, AUC 0.62, p < 0.05). CONCLUSIONS: In
      analysed group the symptoms of depression, higher baseline right ventricular
      diastolic diameter and higher baseline D-dimers level were independent predictors
      of MACE.

PMID- 18619180
TI  - Polycystic kidney disease: will it become treatable?
AB  - Polycystic kidney disease is an inherited multisystem disorder. It causes
      progressive loss of kidney function, flank pain, urinary tract infection,
      arterial hypertension and vascular abnormalities. Until the present time the
      treatment of polycystic kidney disease has been symptomatic. New approaches based
      on cell culture of cyst wall epithelia and on the discovery of polycystins 1 and
      2 have lead to novel treatment protocols to attack the origin of the disease.
      These protocols involve vasopressin antagonists, rapamycin and somatostatin at
      the present time.

PMID- 18619181
TI  - Screening and surveillance for colorectal neoplasia: uncertainties of
      colonoscopic management.
AB  - Over the past decade the use of screening and surveillance modalities has been
      associated with a small but significant decrease in the incidence of colorectal
      cancer and an increase in curability of lesions that are found. Although
      consensus-based international guidelines have stressed the variety of possible
      diagnostic options that can serve this purpose, in many countries colonoscopy
      withremoval of all polyps has become the test of choice. The evidence-base for
      this choice is largely derivative rather than direct and prospective, and many
      uncertainties remain in its use as a primary screening modality. This review
      examines our current guidelines relative to risk stratifying the populations
      offered the test; the onset, interval, and discontinuation of testing; and the
      important role of operator variability in outcome.

PMID- 18619182
TI  - Mesothelial cell transplantation.
AB  - Mesothelial cells are an integral part of the peritoneum and play an important
      role in maintaining its structural and functional properties. In the recent years
      a number of studies on mesothelial cells have been performed to evaluate the
      localization, secretional properties and the ability of regeneration and
      transdifferentiation of these cells. They are also involved in the repair of the
      peritoneum damage following surgery or peritonitis. Mesothelial cells produce
      several cytokines, growth factors and extracellular matrix components, possessing
      anti-inflammatory and immunomodulatory properties. Because of their plasticity,
      these cells are able to form a new cell type like fibroblast, endothelial and
      smooth muscle cell, chondrocyte, osteoblast, adipocyte or neuron. The first step
      involves mesothelial cell transdifferentiation into progenitor cells with the
      capacity of further differentiation. In this paper the current knowledge
      concerning the mesothelial cell differentiation and transplantation has been
      reviewed. Own mesothelial cells of a patient are used in transplantation. They
      are sampled, cultured in vitro and then they can be used in the prevention and
      treatment of post-operative abdominal adhesions, incisional hernias, repair of
      peritoneal membrane of patients on long-term peritoneal dialysis, the prevention
      of ischemic myocardial damage, nerve regeneration and genetically modified
      recombinant protein secretion. Inevitably, more potential applications of
      transplanted mesothelial cell will be available over the next few years.

PMID- 18619183
TI  - Neuroborreliosis with extrapyramidal symptoms: a case report.
AB  - The disease of Lyme is a tick-borne infection. It involves skin, the nervous
      system, joints and the heart. Spirochaeta Borrelia burgdorferi is the etiologic
      agent of the disease. In the majority of cases, clinical symptoms, like migrating
      erythema, occur from 3 to 30 days, sometimes to 3 months after a bite from a
      tick. The early disseminated infection involves multiple migrating erythema,
      neuroborreliosis, arthritis, myocarditis and other organ-related symptoms. The
      late stage of chronic infection involves chronic atrophic leg dermatitis,
      neurological and rheumatological symptoms, and other organ-related symptoms which
      persist for above 12 months. The diagnosis of the disease of Lyme is based upon
      specific clinical symptoms confirmed by serologic tests. The two-step diagnostic
      protocol including the ELISA method, confirmed by the Western-blot test, is
      optimal. The present article describes a case of a 59-year-old man, a computer
      specialist, who often spends his free time walking in woods for recreation, and
      who was bitten by a tick 3 years before hospitalization. The bite resulted in
      migrating erythema that subsided without antimicrobial treatment. In spite of
      this, the man had not changed his hobby exposing himself to bites from ticks. One
      year later, multiple migrating erythema and extrapyramidalis symptoms appeared
      without any other organ malfunctions. In the current year, the patient was
      admitted to the Infectious Diseases Hospital, and received antibiotics
      (ceftriaxon) with following neurological improvement. Several months later,
      extrapyramidal symptoms increased. On the day of admission to the hospital, the
      neurologic examination showed abnormalities of upper and lower limbs movements
      (propulsive walking and the right lower leg traction), the right hand tremor,
      pouts of the face, and sleepiness.

PMID- 18619184
TI  - Thyroid-associated orbitopathy in patients with Hashimoto's thyroiditis: a case
      report.
AB  - Thyroid-associated orbitopathy is a set of ophthalmic symptoms resulting from an
      autoimmune process in which the swelling of extraocular tissues leads to
      exophthalmos either caused by hypersecretion and accumulation of
      glycosaminoglycans in the orbit fibroblasts or being the result of inflammatory
      processes in the oculomotor. These changes cause eyeball motility disturbances,
      keratopathy, and the pressure on the optical nerve. Thyroid-associated
      orbitopathy accompanies Graves' disease in most cases, whereas the Hashimoto's
      disease in only 5%. In the present case, other reasons for the exophthalmos such
      as tumors of the orbit and sinuses, intracranial tumors, aneurysms and vascular
      fistulas and orbit tissue inflammation of different etiology were excluded.
      Additional examinations showed that thyrotropin level was 26 microlU/ml (normal
      range 0.27-4.0), antithyroglobulin antibody level was 1763 IU/ml (normal range 0
      115), antithyrotropin antibody level was 4.93 IU/l (normal range 0-1), and anti
      thyroid peroxidase antibody level was 1609 lU/ml (normal range 0-35). An
      ultrasound examination showed a thyroid gland of 9.8 ml volume. A cytological
      presentation obtained by thin-needle aspiration biopsy demonstrated inflammatory
      infiltration of lymphocytes, indicating an autoimmune process. The iodine uptake
      after 24 hours was 9%. The active form of orbitopathy was diagnosed in the
      patient with hypothyreosis in the course of Hashimoto's disease. Moreover, the
      coexistence of another autoimmune disease, pernicious anemia was diagnosed. The
      administration of the methylprednisolone pulse therapy and levothyroxine caused
      remission of ophthalmic symptoms, and euthyreosis was obtained. Our report
      presents a rare coexistence of thyroid orbitopathy and Hashimoto's disease.

PMID- 18619185
TI  - Complications of permanent dual-chamber pacing such as late purulent pacemaker
      pocket infection with broken and looped atrial lead, complicated by pulmonary
      embolism after transvenous lead removal: a case report.
AB  - We present a complication of the infected pacing system extraction by lobular
      pneumonia in a 73-year-old female patient. The pacing system involved DDD
      pacemaker, atrial and ventricular endocardial leads implanted 12 year beforehand.
      The defect of the atrial lead emerged during the pacemaker replacement 4 years
      ago. The diagnosis of the injury cause and its reparation were not undertaken at
      that time. An interruption of the atrial lead which resulted in the formation of
      a loop inside the cardiac chamber was found when purulant pacemaker pocket
      infection had been diagnosed. The patient was referred for the pacing system
      extraction after preoperative specific antibiotic treatment. After a long
      lasting, difficult, two-step leads extraction procedure, pneumonia developed. An
      echocardiogram revealed enlargement of the right atrium and ventricle, with
      elevated pulmonary artery pressure up to 40 mmHg. An atypical chest X-ray with
      the presence of a large pleural liquid volume led to the work-up of hemorrhagic
      complications and postponed the antithrombotic therapy. With the delay of 1.5
      month the pulmonary scintigraphy showed features of pulmonary embolism. The
      embolism was most likely caused by a vegetation mobilized from the endocardial
      lead and/or endocardium during the extraction maneuvers. Before the surgery, the
      vegetations attached to the leads or to the endocardium had not been visualized.
      Anticoagulant therapy with antivitamins K was successful, which resulted in the
      pulmonary pressure normalization. The patient has remained in a good condition
      for the next 3 months of follow-up.

PMID- 18619186
TI  - The low glycemic index diet: new way of eating for all?

PMID- 18619187
TI  - Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in
      preventive cardiology: which drug to use and what to expect in light of the
      ONTARGET trial.

PMID- 18619188
TI  - Diabetes control and pregnancy outcomes in women with type 1 diabetes treated
      during pregnancy with continuous subcutaneous insulin infusion or multiple daily
      insulin injections.
AB  - OBJECTIVES: The aim of the study was to compare diabetes control and obstetrical
      outcomes in pregnant women with type 1 diabetes treated during pregnancy with
      either continuous subcutaneous insulin infusion (CSII) or multiple daily insulin
      injections (MDII). PATIENTS AND METHODS: It was a descriptive, retrospective,
      observational study of 116 Caucasian pregnant women with type 1 diabetes
      mellitus. Thirty women were treated during pregnancy with continuous subcutaneous
      insulin infusion (CSII group) and 86 with multiple daily insulin injections (MDII
      group). RESULTS: Mean age and body mass index did not differ between groups (p
      >0.05). Duration of diabetes was longer in CSII than in MDII group, 12.7 +/- 7.20
      vs. 7.71 +/- 6.13 years, respectively (p = 0.0005). There were no differences
      between the studied groups in glycated hemoglobin (HbA(1c)) levels in the I, II
      and III trimesters of pregnancy - in CSII group 7.41 +/- 1.75, 6.57 +/- 1.09 and
      6.46 +/- 0.87, respectively, in MDII group - 7.71 +/- 2.37, 6.65 +/- 1.18 and
      6.75 +/- 1.21, respectively (p >0.05). There were no severe hypoglycemia and
      diabetic coma. Mean duration of pregnancy, rate of premature deliveries, newborn
      birth weight, incidence of SGA and LGA, and the frequency of neonatal
      hypoglycemia did not differ between groups (p >0.05). The total malformation rate
      was 5.13%, including 2 terminated pregnancies and the frequency did not differ
      between groups (p >0.05). The rate of spontaneous abortions was 16.7% in CSII
      group and 10.3% in MDII (p >0.05). CONCLUSIONS: No apparent relationships between
      mode of insulin therapy and pregnancy outcome were found in type 1 diabetes
      patients.

PMID- 18619189
TI  - Evaluation of PDGF-AB and sP-selectin concentrations in relation to platelet
      count in patients with colorectal cancer before and after surgical treatment.
AB  - INTRODUCTION: Platelet-derived growth factor (PDGF) and P-selectin, the low
      molecular weight proteins located mainly in the platelet alpha-granules, are
      considered to be biologically active markers of platelet (PLT) activation.
      OBJECTIVES: The study objective was to assess levels of PDGF-AB and sP-selectin
      in relation to PLT blood count in patients with colorectal cancer (CRC) who were
      examined before and after radical surgical treatment of the cancer. PATIENTS AND
      METHODS: The study involved 38 CRC patients including B1 - 20 patients (T(2
      3)N(1)M(0)), B2 -18 patients (T(2-3)N2M0) and 24 age and sex-matched healthy
      subjects (the control group). Blood samples were collected from the antecubital
      vein prior to and 3 months after the radical surgery. PDGF-AB and souble (s)P
      selectin, the markers of PLT activation, were determined by the immunoenzymatic
      methods. RESULTS: In CRC patients, the levels of PDGF-AB and sP-selectin were a
      few times higher, whereas the PLT count was lower as compared to the control
      group. Moreover, these levels were statistically much higher before, compared to
      those after the surgery, in patients with a higher grade of clinical and
      histological differentiation (p <0.05) as well. However, no positive correlation
      was found between the PLT count and the PDGF-AB and sP-selectin levels.
      CONCLUSIONS: High levels of PDGF-AB and sP-selectin, the sensitive markers of PLT
      activation prior to surgical treatment seem to indicate cancer tissue as the
      source of both PDGF and sP-selectin. For this reason, PDGF-AB and sP-selectin
      determination may help in early non-invasive CRC evaluation in the future.

PMID- 18619190
TI  - Falciparum malaria in a South African tertiary care hospital.
AB  - INTRODUCTION: This study was a retrospective case series over one year.
      OBJECTIVES: The purpose was to review the clinical presentation, travel history,
      laboratory findings and outcome of Plasmodium falciparum malaria. PATIENTS AND
      METHODS: The study was conducted in the medical wards of Dr. George Mukhari
      Hospital, a teaching hospital in South Africa that serves mainly black patients.
      Fifty-nine patients were evaluated. The mean age was 34 years. Twenty-three
      patients (39%) had strictly defined severe malaria. Ninety-eight percent acquired
      Plasmodium falciparum in Sub-Saharan Africa. The death rate was 1.7%. Virtually
      all patients had a travel history obtained in the emergency department and the
      diagnosis was confirmed in all cases within 24 hours of admission. RESULTS: In
      our study population, the differences in the percent parasitemia, platelet count,
      haemoglobin and bilirubin were not statistically significant between the cases
      with severe and those with less severe malaria. CONCLUSIONS: Plasmodium
      falciparum malaria should not carry a high mortality in adequately equipped
      centers, when the diagnosis is made early and therapy is instituted promptly.

PMID- 18619191
TI  - Prophylaxis and therapy of central nervous system involvement in adult acute
      lymphoblastic leukemia: recommendations of the Polish Adult Leukemia Group.
AB  - The central nervous system (CNS) is one of the most frequent extramedullary
      locations of adult acute lymphoblastic leukemia (ALL), affecting approximately 5%
      of patients at diagnosis. T-lineage ALL, high initial leukocyte counts and
      mediastinal involvement are the predisposing factors. In case of relapse, if no
      prophylaxis was administered, the rate of CNS involvement reaches 30-50%. As the
      prognosis of patients with isolated or mixed CNS relapse is particularly poor,
      adequate prophylaxis seems critical. The treatment comprises intrathecal
      cytostatics, cranial and spinal cord irradiation, as well as systemic
      chemotherapy including agents penetrating to the CNS. This strategy allows a
      reduction in CNS relapses to less than 5% of cases. Compliance to the
      prophylactic protocols should be one of the principles in the treatment of adult
      ALL.

PMID- 18619192
TI  - Allergy and asthma: from the bedside to the bench and international actions.
AB  - The interdependence of the bench to the bedside has been demonstrated for many
      years. The example in allergy and asthma has been used to show how clinical
      observations can be dissected by epidemiologic and basic scientific studies
      leading to a better concept of rhinitis, asthma and their comorbidities. From
      research, public health programs can be designed.

PMID- 18619193
TI  - Can a physician refuse to help a patient? American perspective.
AB  - Refusal to help means for most people declining to accept the duty to treat. The
      reasons for refusing to help and how we think about these reasons from an ethical
      and professional viewpoint are outlined by considering ethical principles, an
      historical perspective, the law, societal contracts, medicine as a moral
      enterprise, professional codes, a physician's personal beliefs, reasons for
      refusing to help and physician discretion. Refusing to help a patient is not
      consistent with the ethical principle of beneficence, the concept of the primacy
      of patient welfare or the obligation of the profession to care for the sick.
      However duty to treat should not be exploited by institutions or place physicians
      in circumstances that they consider morally, psychologically or physically
      unacceptable. Following the principle of distributive justice, physicians are
      obligated to participate in the public debate to ensure that all patients have
      their needs met by developing or improving health care systems and addressing the
      new ethical questions that are likely to be generated.

PMID- 18619194
TI  - Which drug to be used in smoking cessation?
AB  - There are 3 first-line medications for smoking cessation i.e. nicotine
      replacement therapy (NRT), varenicline (a partial nicotine receptor agonist) and
      slow-release (SR) bupropion. All 3 agents approximately double 1-year quit rates
      when used for 3 months, although varenicline seems to be a little more
      efficacious than bupropion SR. An un-blinded study comparing varenicline with
      nicotine patches are analysed in details and it is concluded that the validity of
      that study is low regarding the relative efficacy of varenicline versus NRT.
      Depression and suicidal attempts have been reported with varenicline use but it
      is probably not induced by varenicline but by the quitting process per se. It is
      recommended that the first agent to be used in smoking cessation should be NRT as
      it is the best documented product with mild side effects. It might be optimal to
      combine the patch with either gum, inhaler, sublingual tablets or nasal spray. In
      subjects that have failed with NRT, varinicline should be the choice. Bupropion
      SR is preferred to subjects with depression or smokers who have failed with the
      previous two agents, due to the many contra-indications and side effects of
      bupropion SR. With one of the 3 agents combined with follow-up visits with
      counselling, one can expect a 1-year quit rate around 20-25%.

PMID- 18619195
TI  - Polymyalgia rheumatica: clinical picture and principles of treatment.
AB  - Polymyalgia rheumatica (PMR) is a common disease of the elderly. It is
      characterized by pain and stiffness in the neck, shoulders and the pelvic girdle.
      In most cases erythrocyte sedimentation rate and C-reactive protein levels are
      highly elevated. Polymyalgia rheumatica is frequently associated with giant cell
      arteritis. Steroids are the standard treatment for PMR but their dosage requires
      adjustment depending on clinical picture, co-morbid conditions and adverse
      effects. The most prominent features of the disease as well as the main
      principles of treatment are presented.

PMID- 18619196
TI  - Wegener's granulomatosis effectively treated with rituximab: a case study.
AB  - Wegener's granulomatosis (WG) is a granulomatous disorder associated with
      systemic necrotizing vasculitis. Wegener's granulomatosis predominantly involves
      the upper airways, lung and kidneys. The disease is often associated with
      cytoplasmic antineutrophil cytoplasmic antibodies (cANCA). B lymphocytes are
      potential cANCA producers and there is an evident correlation between cANCA
      titre, severity of the disease and response to treatment. Wegener's
      granulomatosis usually begins with symptoms limited mostly to the upper and/or
      lower respiratory tracts and may transform into the generalized phase,
      characterized by systemic necrotizing vasculitis. If left untreated, it can turn
      fulminant with poor prognosis. The severe form of the disease is usually treated
      with a combination of cyclophosphamide and corticosteroids. In refractory cases,
      rituximab that binds to CD20 expressed on B-cells should be considered. We
      presented a case of a 38-year-old woman with severe form of WG, refractory to
      standard therapy. Despite the standard treatment with cyclophosphamide and
      corticosteroids and the addition of infliximab with methotrexate, progression of
      the disease was observed. Exacerbation affected mainly the lungs and caused the
      gradual destruction of pulmonary tissue and development of respiratory
      insufficiency. Rituximab (500 mg) was given intravenously every week in four
      infusions, causing a partial remission of WG and the arrest of lung
      deterioration. The following administration of 500 mg was given every two weeks,
      which induced the remission of WG and enabled the patient to return to her normal
      activity and work. Such treatment appeared to be successful and prevented severe
      pulmonary involvement.

PMID- 18619197
TI  - Coccidioidomycosis in a 38-year-old man: a case report.
AB  - The present article describes a case of acute pulmonary coccidioidomycosis in a
      38-year-old man, a research worker. The disease started during the patient stay
      in Arizona, USA, and clinical symptoms persisted after his return to Poland.
      Acute coccidioidomycosis is one the clinical manifestations of Coccidioides
      immitis strain endemic infections occurring in the south-western regions of USA
      including California (mainly San Joaquin Valley), Western Texas, New Mexico and
      the desert areas of Arizona, and Central and South America. The native
      environment of Coccidioides immitis is soil penetrated by rodents. People,
      domestic and wild animals suffer from coccidioidomycosis. The infection rate in
      endemic areas is about 2-4% a year in the healthy population. Coccidioidomycosis
      can be observed in non-endemic areas due to population mobility and in
      immunocompromised patients. The Coccidioides immitis infection is caused by
      inhaled airborne fungal spores and it may occur as primary pulmonary (acute or
      chronic) asymptomatic form, meningitis, or disseminated disease. The clinical
      symptoms of coccidioidomycotis like acute pulmonary manifestations may resemble
      typical, resistant to empiric antibiotic treatment of bacterial pneumonia. In
      healthy subjects, pulmonary coccidioidomycosis may occur as asymptomatic
      infection, which resolves spontaneously without medication. Sometimes, slight
      shadows like local fibrosis and cavities may be visible on the chest X-ray. The
      Coccidioides immitis infection in people with immunological deficiency syndromes,
      e.g. HIV/AIDS, manifests itself as disseminated disease and may lead to severe
      complications including death.

PMID- 18619198
TI  - [Laboratory diagnosis of toxoplasmosis in children in the Omsk Region].

PMID- 18619199
TI  - [Diagnostic efficiency of the rapid "SEROCHEK MBT" test for the determination of
      antibodies to mycobacterium tuberculosis].
AB  - The informative value of the rapid "SEROCHEK MBT" test (Zephyr Biomedicals,
      India) was assessed to confirm the presence of serum Mycobacterium tuberculosis
      antibodies in vitro. Analysis of the findings indicates that pulmonary
      tuberculosis can be verified by the "SEROCHEK" test only in 31% of the examinees.
      The tests have proven to be least informative in minor forms of tuberculosis (9%)
      and to be more informative in disseminated processes (41.7%) and chronic
      pulmonary tuberculosis (75%). The findings (9% positive serological tests in
      minor forms of tuberculosis) suggest that the "SEROCHEK MBT" test shows a low
      sensitivity in confirming the presence of serum Mycobacterium tuberculosis
      antibodies and therefore a low informative value as a method for the rapid
      diagnosis of tuberculosis.

PMID- 18619200
TI  - [Neutrophilic nitroblue tetrazolium reduction test in the diagnosis of neonatal
      bacterial infection].
AB  - The kinetics of a spontaneous peripheral blood neutrophilic nitroblue tetrazolium
      test (NBT-test) has been studied in neonatal infants. The reaction is shown to
      come to an end after 60-min reaction mixture thermostating, thereafter the
      proportion of activated neutrophils (PAN) does not change (PAN(infinity)). The
      reaction is described using the first-order kinetic equation that is similar to
      that having the rate constant k1. The calculations of PAN(infinity) and k1 allow
      a differential diagnosis of bacterial infections with and/or without pneumonia.

PMID- 18619201
TI  - [T-cell responsiveness to specific group A streptococcus antigens in patients
      with recurrent erysipelas].
AB  - Peripheral blood leukocytic migratory activity (LMA) was studied in 51 patients
      with recurrent erysipelas versus 63 patients with primary erysipelas. To reveal
      LMA, the authors employed in vitro a screening cell migration test as an
      indicator of the cooperation of T and B lymphocytes and macrophages, by
      stimulating with polysaccharide A, surface proteins, L-antigen, hyaluronidase,
      streptolysine-O, and a complete set of Grasse S. pyogenes. In patients with
      recurrent erysipelas, undulating LMA changes were found in the course of the
      disease in response to the stimulation with partial specific S. pyogenes
      antigens. There were differences in the time course of LMA changes, when
      stimulated with specific surface streptococcus antigens and with components of
      streptococcus with toxic activity. Significant LMA differences were found in
      relation to the pattern of a local process: active LMA changes from acceleration
      to suppression in the erythematous-hemorrhagic form and hyperergic reactions of
      LMA acceleration in the bullous-hemorrhagic one.

PMID- 18619202
TI  - [Polymorphism of congenital malformation-associated genes in children: a review
      of literature].

PMID- 18619203
TI  - [Diagnostic value of lipoprotein electrophoresis in somatic diseases--secondary
      hyperlipoproteinemias (Lecture 2)].

PMID- 18619204
TI  - [Study of plasma megamolecular complexation by laser correlation spectroscopy].

PMID- 18619205
TI  - [Human serum insulin-binding component in health and in type 1 diabetes
      mellitus].
AB  - Serum-affine components have been detected in the sera of healthy donors and
      patients with diabetes mellitus. Human serum has been ascertained to contain
      insulin-binding component. The latter has not been shown to be immunoglobulin,
      i.e. it contains no insulin-specific antibodies. The experimental findings
      suggest that there are human serum proteins that are involved in the transport of
      insulin.

PMID- 18619206
TI  - [A relationship of squamous-cell metaplasia with the pattern of the course of a
      respiratory epithelial dysplastic process].
AB  - The morphological signs of squamous-cell metaplasia were revealed in 65 out of
      193 patients with varying bronchial mucosal changes. A follow-up of the patients
      indicated that in the group of patients with epithelial dysplasia without
      squamous-cell metaplasia, the prognosis was good in 65.6% of cases. In the group
      of patients with epithelial dysplasia and squamous-cell metaplasia, the prognosis
      was poor in 86.2% of cases.

PMID- 18619207
TI  - [Leukocytic functional and metabolic activity in patients with morphea guttata].
AB  - Cytochemical techniques were used to study the functional and metabolic activity
      of neutrophilic granulocytes in 36 patients with morphea guttata. The levels of
      major microbicidal components (cationic protein, glycogen, lipids,
      myeloperoxidase, and acid phosphatase) were measured during a pathological
      process. Extremely important regularities were revealed: with active clinical
      manifestations, there was a significant inhibition of the activity of
      myeloperoxidase, the level of cationic proteins, intracellular lipids and a
      considerable increase in the activity of acid phosphatase and the content of
      glycogen in the cells; normalization of leukocytic metabolic activity occurs at
      remission. The authors show it possible to clinically use the determination of
      the major components of the microbicidal system in order to assess nonspecific
      responsiveness in patients with morphea guttata for diagnostic and prognostic
      purposes.

PMID- 18619208
TI  - [Examination practice in the licensing and accreditation of medical organizations
      rendering laboratory services].

PMID- 18619211
TI  - Imaging in oncology. Preface.

PMID- 18619212
TI  - Anatomic, physiologic and metabolic imaging in neuro-oncology.

PMID- 18619213
TI  - Imaging of spinal tumors.

PMID- 18619214
TI  - PET imaging of brain tumors.

PMID- 18619215
TI  - Extracranial head and neck neoplasms: role of imaging.

PMID- 18619216
TI  - Imaging of thoracic malignancies.

PMID- 18619217
TI  - Imaging of mediastinal tumors.

PMID- 18619218
TI  - Imaging cardiac tumors.
AB  - Cross-sectional imaging techniques such as echocardiography and MRI provide
      important information about cardiac masses. Echocardiography can provide
      information about cardiac tumors with regard to size, location and response to
      treatment. MRI is helpful in determining tumor extent, mobility, location, local
      invasion, relationship with critical cardiac and non-cardiac structures and tumor
      characterization. For pericardial tumors and metastatic lesions, MRI appears to
      be the imaging modality of choice.

PMID- 18619219
TI  - Diagnostic imaging and image-guided interventions of hepatobiliary malignancies.

PMID- 18619220
TI  - Recent advances in imaging of pancreatic neoplasms.

PMID- 18619221
TI  - Imaging of colorectal carcinoma.

PMID- 18619222
TI  - Imaging of primary malignant tumors of peritoneal and retroperitoneal origin.
AB  - Peritoneal carcinomatosis and metastatic involvement of the retroperitoneum are
      relatively common manifestations of many organ-based malignancies and
      lymphoproliferative disorders. Primary malignancies of peritoneal and
      retroperitoneal origin occur much less frequently, and can be difficult to
      distinguish from metastatic disease. In many cases, a precise diagnosis based on
      imaging findings alone is not possible. However, the imaging features of these
      primary tumors, in combination with the clinical and demographic data, can be
      utilized to narrow the scope of the differential diagnosis. This chapter will
      present the clinical and imaging features of primary peritoneal and
      retroperitoneal tumors arising from the various tissue components that comprise
      the ligaments, mesenteries and connective tissues of these anatomic spaces.

PMID- 18619223
TI  - Imaging of urinary tract tumors.
AB  - In summary, imaging now has an important role in the evaluation of patients with
      invasive bladder cancer. It is useful in staging of bladder cancer, despite
      having some limitations. CT is widely accessible and has enjoyed rapid advances
      in multidetector technology which have far-reaching applications. MRI, due to its
      intrinsic tissue characterization, is reported to have a higher accuracy for
      staging bladder cancer. It is superior to CT in determining the depth of bladder
      wall invasion. CT, as well as traditional MRI, rely on morphological criteria and
      are both useful in the detection of metastases to the lymph nodes, liver and
      bone. MRI, however, can now also take advantage of the tremendous advance in
      lymph node evaluation brought about by the advent of USPIO nodal imaging. MRI is
      also considered superior in follow-up of patients with bladder cancer post
      therapy as it can distinguish biopsy changes more accurately than CT. In
      conclusion, it is clear that imaging plays a growing and increasingly important
      role in the evaluation of patients with bladder cancer.

PMID- 18619224
TI  - Current status of imaging for adrenal malignant involvement.
AB  - CT, MRI, PET and PET/CT have all been shown to be clinically useful in
      differentiating benign from malignant adrenal involvement. Image-guided adrenal
      biopsy should be considered if needed for treatment planning and for the now
      relatively uncommon lesions that remain indeterminate by imaging.

PMID- 18619225
TI  - Recent advances in imaging of male reproductive tract malignancies.

PMID- 18619226
TI  - Imaging of malignant skeletal tumors.

PMID- 18619227
TI  - Radiology of soft tissue tumors including melanoma.

PMID- 18619228
TI  - Reticuloendothelium malignancy: current role of imaging.
AB  - Imaging has an important role in the diagnosis and staging of patients with
      lymphoma, with a major influence on both patient management and outcome. CT is
      probably the most widely used modality in patients with lymphoma bur MRI is
      probably as useful as CT in the initial work-up of the patient. Finally, PET/CT
      can detect residual disease in patients post-treatment better than both CT and
      MRI and is playing an increasing role in the imaging of patients with lymphoma.

PMID- 18619229
TI  - Pediatric malignancies: synopsis of current imaging techniques.

PMID- 18619230
TI  - Interventional Radiology in oncology.

PMID- 18619231
TI  - Breast tumor imaging.

PMID- 18619232
TI  - [Comparison of the content of effective components between tree peony wild
      species and main cultivars].
AB  - OBJECTIVE: To determine the content of paeonol and paeoniflorin in wild tree
      peony species and main medicinal cultivars in order to provide scientific
      foundations for the industrialization of tree peony cortex. METHODS: HPLC was
      used to compare the effective content of different resources. RESULTS: (1) The
      content range of paeonol and paeoniflorin of 7 wild species was 0.10%-0.61% and
      2.22%-5.57%, respectively; (2) The content range of paeonol and paeoniflorin of
      all cultivars from different producing area was 0.33%-1.43% and 1.60%-2.85%; (3)
      The content range of paeonol and paeoniflorin of different cultivars in the same
      place (Changping, Beijing) was 0.27%-0.75% and 1.87%-3.96%; (4) The content range
      of paeonol of cultivars from the same area was 0.34%-1.10%. There was no
      significant difference of relative content of paeoniflorin from the same areas.
      CONCLUSION: The relative content of main medicinal components of wild species was
      not higher than cultivar; the differences were significant among cultivars; the
      relative content of paeonol of 'JSF' was high; more attention of choosing
      cultivars and producing areas should be paid in tree peony cortex producing.

PMID- 18619233
TI  - [Comparison of tanshinone IIA in Radix Salviae Miltorrhizae from Shandong].
AB  - OBJECTIVE: To compare the contents of tanshinone IIA in Radix Salviae
      Miltorrhizae from different species, production places and collecting time, for
      study its quantity from Shandong. METHODS: HPLC method was used. RESULTS: The
      contents of tanshinone IIA in Radix Salviae Miltorrhizae of Shandong ranged from
      0.330%-0.726%. CONCLUSION: Setting the contents of tanshinone IIA as index, the
      quantity of Salvia miltiorrhiza Bge. f. alba C. Y. Wu et H. W. L. is better than
      Salvia miltiorrhiza Bge.. The genuine production place-Mengyin is the best
      planting area; the plantable place is mountaing district hillyland. Planting in
      plain region is inadvisable; the best collecting time is middle September.

PMID- 18619234
TI  - [Study on chemical constituents and anti-bacterial activity of volatile oil from
      seed of Aquilaria sinensis].
AB  - Volatile oil from the seed of Aquilaria sinensis was extracted with Petroleum
      ether. Anti-bacterial bioassay of the oil against methicillin-resistant
      Staphylococcus aureus (MRSA) was carried out by paper disco diffusion method. The
      result showed that the oil possessed inhibitory activity towards MRSA. 19
      compounds of the volatile oil were identified by GC-MS analysis.

PMID- 18619235
TI  - [Optimum of polysaccharide distillation on scrap Cordyceps militaris medium].
AB  - A mass of scrap Cordyceps militaris solid culture medium could not be utilized
      better. In this test, using orthogonal design the optimal technique parmeter of
      extracting polysaccharide was 80 degrees C, two times, in twenty times of water,
      and 120 minutes each time. Temperature was the most important factor. The
      referenced data could be provided to depurative production of Cordyceps militaris
      and resource utilization.

PMID- 18619236
TI  - [Identification on three kinds of Diphylleia sinensis (I)].
AB  - OBJECTIVE: In order to provide reference for the development of quality standards
      and distinction of authenticity, some sources of Diphylleia sinensis Li. in the
      market were identified by sampling. METHODS: To identify the traits and
      microscopic features of six batches of Diphylleia sinensis Li. in the market.
      RESULTS: They were the dried rhizome of Diphylleia sinensis Li., Dysosma
      versipellis (Hance) M. Cheng and D. pleiantha (Hance) Woods. CONCLUSION: The
      differences in traits and microscopic features of them are obvious.

PMID- 18619237
TI  - [Studies on chemical constituents from Anoectochilus roxburghii].
AB  - OBJECTIVE: To investigate the chemical constituents from Anoectochilus
      roxburghii. METHODS: The compounds were isolated and purified by repeated column
      chromatographies with silica gel, Macroporous resin and Sephadex LH-20, and their
      structures were identified by their physical and spectral datas. RESULTS: Ten
      compounds were isolated and elucidated as: beta-D-glucopyranosyl-(3R)
      hydroxybutanolide (I), stearic acid (II), palmitic acid (III), beta-sitosterol
      (IV) and succinic acid (V), p-hydroxy benzaldehyde (VI), daucosterol (VII), and
      methyl 4-beta-D-glucopyranosyl-hutanoate (VIII); as well as p-hydroxy cinnamic
      acid (IX) and o-hydroxy phenol (X) were identified. CONCLUSION: Compound I ,VIII,
      X are firstly isolated from this species.

PMID- 18619238
TI  - [Study on the chemical constituents of liposoluble steroidal and triterpenoid
      compounds from the stem and bark of Macaranga hemsleyana].
AB  - OBJECTIVE: to research the chemical constituents of the liposoluble compounds
      from the stem and bark of Macaranga hemsleyana Pax & Hoffm. METHODS: Five
      compounds were obtained by silica chromatography and preparative TLC from the
      stem and bark of Macaranga hemsleyana Pax & Hoffm., and the chemical structures
      of these compounds were identified by modern spectroscopy as well as physico
      chemical analysis. RESULTS: These compounds were identified to be beta-Sitosterol
      (1), Stigmast-4-en-3-one (2), Stigmast-4-en-3,6-dione (3), 3beta-O-acetyl
      aleuritolic acid (4) and Canophyllol (5). CONCLUSION: The liposoluble fractions
      of Macaranga hemsleyana Pax & Hoffm. are mainly steroidal and triterpenoid
      compounds.

PMID- 18619239
TI  - [Study on chemical constituents isolated from Juncus effuses].
AB  - OBJECTIVE: To study the constituents isolated from Juncus effuses Linn.. METHODS:
      The compounds were isolated through chromatographic approaches, such as Silica
      gel. CC, Sephadex LH-20 and were identified by a combination of spectroscopic
      methods (UV, MS, 1H-NMR, 13C-NMR and NOE). RESULTS: 8 kinds of compounds were
      identified which included four flavonoids, luteolin (I), eriodictyol (II), 2',
      5', 5, 7-tetrahydroxyflavone (III), glucoluteolin (IV); two aromatic compounds,
      methyl p-hydroxybenzoate (V), vanillic acid (VI); a fatty acid, hexadecanoic acid
      (I) and an alkane, n-Tetradecane (VIII). CONCLUSION: Compound II, III, V, VI,
      VII, VIII were firstly isolated from this plant.

PMID- 18619240
TI  - [Study on main effectual ingredient content in fresh juice of Panax
      quinquefolium].
AB  - OBJECTIVE: To study on the comprehensive utilization value from fresh juice of
      Panax quinquefolium L. METHODS: The total saponins of Panax quinquefoliuml L. 9
      kinds of trace elements were determined in fresh juice with ICP-AES, as well as
      16 kinds of ammonia acids. RESULTS: The physiologically active. Panax
      quinquenoside was affluent in fresh juice. There were many kinds of trace
      elements and ammomnia acid in fresh juice. CONCLUSION: Fresh juice of Panax
      quinquefolium L. is a kind of valuable resource.

PMID- 18619241
TI  - [Analysis on the chemical compositions of the volatile oil from ultramicro-powder
      and common grinding powder of Cinnamomum cassia].
AB  - OBJECTIVE: To analyse and compare the chemical compositions in the volatile oil
      from Utramicro-powder and Common Grinding Powder of Cinnamomum. METHODS: The
      volatile oil was extracted by steam-stilling and analyzed by GC-MS. The relative
      content of each component was calculated by area normalization method. RESULTS:
      34 and 19 peaks were isolated from Ultramicro-powder and Common Grinding Powder
      of Cinnamomum respectively. All of them were identified. CONCLUSION: The chemical
      components of the volatile oil from Ultramicro-powder and Common Grinding Powder
      of Cinnamomum are reported, the results here provides scientific proof for the
      application in external preparation of Cinnamomum.

PMID- 18619242
TI  - [Study on oil-soluble components obtained from the fruit of Evoldia rutaecarpa].
AB  - OBJECTIVE: To extract and isolate the biologic-active components of the oil
      soluble components obtained from the fruit of Evodia rutaecarpa. METHODS: Various
      chromatographic techniques were used to isolate and purifie the biologic-active
      components, the IR and NMR spectra were used to identify the structure of this
      compound from Evodia rutaecarpa, and the content and the chemical structure was
      calibrated with a standard mixture was by TLC. RESULTS: A crystal compound was
      isolated from the Evodia rutaecarpa of Rutaceae, and was elucidated as oleanolic
      acid. CONCLUSION: The main chemical constituents of oil-soluble components
      obtained from the fruit of Evodia rutaecarpa are terpenoid compounds, the content
      of oleanolic acid is 1.8%.

PMID- 18619243
TI  - [Determination of the total content of astragaloside IV in Radix Astragali].
AB  - OBJECTIVE: To determine the total content of astragaloside IV in Radix Astragali.
      METHODS: The measurement conditions were used as follows: Irregular C18 (4.6 mm x
      250 mm, 5 microm) column; mobile phase: acetonitrile-water (32:68); flow rate:
      1.0 ml/min; detector: ELSD 2000; the temperature of drift tube: 100 degrees C;
      gas flow: 2.7 L/min. RESULTS: Eight batches of Radix Astragali from different
      sources were determined. The stability, precision and reproducibility of the
      method were studied, RSD <3%. CONCLUSION: There is great difference between the
      content of astragaloside IV in Radix Astragali by different processing methods.

PMID- 18619244
TI  - [Determination of chlorogenic acid and total caffeoylquinic acid in 6 Folium
      Lonicerae].
AB  - OBJECTIVE: To determine the contents of chlorogenic acid and total caffeoylquinic
      acid in 6 Folium Lonicerae in Sichuan province and Chongqing city for evaluating
      the quality of them. METHODS: The HPLC analysis and spectrophotometry analysis
      were used. RESULTS: The contents of chlorogenic acid and total caffeoylquinic
      acid in 6 Folium Lonicerae had been determined. CONCLUSION: The method is
      accurate, simple and has a good reproducibility. The results can be used as a
      reference for the reasonable medication, quality control and further study of
      Folium Lonicerae.

PMID- 18619245
TI  - [The study of Xuanshen on ventricular remodeling and cardiac endothelin-1
      expression in rats treated with pressure-overload].
AB  - OBJECTIVE: To investigate the influence of Xuanshen on cardiac endothelin-1
      expression, ventricular remodeling and its mechanism in rats treated with
      pressure-overload. METHODS: The ventricular remodeling model was induced by
      abdominal aortic stenosis in rats. Meanwhile, sham-operated rats were established
      as the control group. 8 weeks after drug interference, heart rate (HR), systolic
      blood pressure (SBP), diastolic blood pressure (DBP), left ventricular weight and
      heart weight index (LVWI and HWI), the activity of superoxide dismutase (SOD),
      cardiac endothelin-1 concentration and its gene expression were determined.
      RESULTS: Compared with those of sham-operated rats, the HR, SBP, DBP, LVWI and
      HWI of the model rats were increased significantly. The activity of SOD
      decreased, the concentration of cardiac endothelin-1 and its gene expression
      increased. In groups treated with Xuanshen, the HR, SBP, DBP, LVWI and HWI
      declined and the activity of SOD was improved. Moreover, the concentration of
      cardiac endothelin-1 and its gene expression decreased. CONCLUSION: Pressure
      overload may induce oxidative stress and over-expression of cardiac endothelin-1.
      Xuanshen can inhibit ventricular remodeling. The mechanism may be related to the
      inhibition of oxidative stress and down regulation of endothelin-1 expression.

PMID- 18619246
TI  - [Effect of Rehmannia glutinosa Libosch water extraction on gene expression of
      proinsulin in type 2 diabetes mellitus rats].
AB  - OBJECTIVE: To investigate the mechanisms of treating 2-DM by Rehmannia glutinosa
      Libosch water extraction (RGLE). METHODS: The mRNA level of proinsulin in rats
      panreas tissue was examined by semi-quatitativa RT-PCR,and the protein was
      measured by SDS-PAGE. RESULTS: The mRNA and protein expressions of proinsulin in
      RGLE group were higher than those of diabetic model group (P<0.01). The levels of
      FPG decreased. FINS,IS, HbetaCI increased (P<0.01). CONCLUSION: It may be the
      mechanism how the RGLE to decline high FPG and cure the 2-DM.

PMID- 18619248
TI  - [Effects of glycyrrhizin on the expression of hepatitis B virus and Toll like
      receptors 2,4 in HepG2.2.15 cells expressing low HBsAg].
AB  - OBJECTIVE: To investigate the effects of glycyrrhizin (GL) on the expression of
      hepatitis B virus e antigen (HBeAg), HBV DNA, Toll-like receptors 2,4 (TLR2,4)
      and proliferation of cells in HepG2.2.15 cell line. METHODS: Real-time PCR
      examined HBV DNA, ELISA examined HBsAg, HBeAg and MTT examined the proliferation
      of cells. FCM examined the positive percent of cells expressing TLR2,4 before and
      after stimulated with GL, in contrast to the blank group. RESULTS: The expression
      of HBsAg was low in the cell line, so e antigen was studied. The total HBeAg mean
      was significantly difference on the second day after stimulated (P<0.01), but
      only in the group with 400 microg/ml HBeAg decreased significantly in contrast to
      the blank group (P<0.05), the group with 800 microg/ml increased significantly in
      contrast to the other groups (P<0.01). The total HBV DNA mean on the third day
      after stimulated was significant, only the group with 50 microg/ml decreased in
      contrast to the blank group, but P>0.05, the other four groups increased. The
      intensity of TLR4 expression in the cells was significantly higher than that of
      the control group (P<0.05), both of total mean TLR2,4 increased significantly
      (P<0.01). The four groups except the group with 200 microg/ml increased
      significantly in no dose-dependent manner (P<0.05). GL in three goups under 200
      microg/ml all could make cells proliferate, but only 200 microg/ml group had
      significant difference compared to the blank group (P<0.05). Both 400 and 800
      microg/ml groups inhibited the growth of cells (P<0.01). The proliferation of
      cells were notably negative correlated with the expression of HBeAg, HBV DNA
      (P<0.05). CONCLUSION: The study suggestes GL could inhibit or promote HBV DNA
      replicating and e antigen secreting in mutative HepG2.2.15 cell line, the
      correlation between the proliferation of cells and the both are negative. GL
      could upregulate TLR2,4 in no dose-dependent manner. Influencing HBV maybe have
      no correlation to up regulating TLR2,4 by GL at least in vitro.

PMID- 18619247
TI  - [Hypoglyceminc effect of flavonoids from Prinsepia utilis on alloxan-induced
      diabetic mice].
AB  - OBJECTIVE: To evaluate the hypoglycemic effect of flavonoids from Prinsepia
      utilis Royle in alloxan-induced diabetic mice. METHODS: The hypoglycemic effects
      were investigated in alloxan-induced diabetic mice after oral administration of
      300 mg/kg of flavonoids from Prinsepia utilis Royle for four weeks. The blood
      glucose (GLU), total cholesterol (TC), triglyceride (TG), very low density
      lipoprotein cholesterol (VLDL-C), alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), blood urea nitrogen (BUN) and body weight of mice were
      determined. RESULTS: Flavonoids from Prinsepia utilis Royle had influence on body
      weight increasing of diabetic mice in three weeks, but had no influence in the
      fourth week. Flavonoids from Prinsepia utilis Royle exhibited hypoglycemic
      effects. Among these fractions, flavonoids from Prinsepia utilis Royle
      significantly reduced GLU, TG and AST level in diabetic mice compared with model
      control group (P<0.01), markedly reduced VLDL-C, ALT and BUN level in diabetic
      mice compared with model control group (P<0.05), but had little influence on TC.
      CONCLUSION: Flavonoids from Prinsepia utilis Royle possess significant
      hypoglycemic activities, they can improve hypothepatia of diabetic mice and have
      protective effect on renal function of diabetic mice.

PMID- 18619249
TI  - [Study on the effect of Part III from Cynomorium songaricum on immunosuppressive
      mice induced by cyclophosphamide].
AB  - OBJECTIVE: To study the immunomodulatory effect of Part III of Cynomorium
      songaricum Rupr. on the immunosuppressive mice. METHODS: The immunity-deficiency
      model was induced by intraperitoneal injection of cyclophosphamide (CTX) at the
      dose of 100 mg/kg in mice; all the animals were divided into normal control
      group, immunity-deficiency model group, Part III treated group (300 mg/kg) and
      positive control group (TSPG, 300 mg/kg). The hemogram of peripheral blood, the
      index of immune organs, the phagocytosis activity of macrophage, the content of
      serum hemolysin were measured. RESULTS: The index of organs, the phagocytosis
      activity of macrophage and the content of serum hemolysin in the model group
      increased after administrated of Part III. CONCLUSION: Part III from Cynomorium
      songaricum Rupr. has protective effect on the immunosuppressive mice, which may
      be related to the increasing of humoral immunity and nonspecific immunity.

PMID- 18619250
TI  - [Effects of HuDan Granules on lipid metabolism and antioxidant activity of mice
      with hyperlipidemia].
AB  - OBJECTIVE: To study the effects of HuDan Granules on lipid metabolism and
      antioxidant activity of mice with hyperlipidemia. METHODS: Seventy-eight mice
      were divided into six groups randomly: the normal control group, hyperlipemia
      group, HuDan Granules high, middle, low dose group and the Simvastatin group.
      Besides the normal control group, all the mice in the other groups were fed with
      lipid emulsion for 4 weeks. The Chinese medicine groups were treated with HuDan
      Granules at the dose of 12,6,3 g/kg, the normal control group and hyperlipemia
      group were treated with normal sodium, the Simvastatin group were treated with
      Simvastatin. After 4 weeks, the TC, TG, HDL-C, LDL-C, SOD, GSH-Px and LPO in
      serum were measured. RESULTS: HuDan Granules groups could significantly decrease
      the serum TC, TG, HDL-C in the experimental hyperlipidemia mice, and markedly
      increase the level of serum HDL-C. Mean level of serum LPO in the experimental
      groups treated by HuDan Granules at different dosages were much lower than that
      in hyperlipidemia group (P<0.05), but higher than the Simvastatin group (P<0.05).
      And the SOD and GSH-Px activities of serum in the group of HuDan Granules were
      much higher than those in hyperlipidemia group and the Simvastatin group
      (P<0.05). CONCLUSION: HuDan Granules can regulate lipid metabolism, enhance the
      antioxidation and reduce the lipid peroxidation in mice with hyperlipidemia.

PMID- 18619251
TI  - [Study on technical processes for extraction and purification of total
      tanshinones].
AB  - OBJECTIVE: To optimize technical processes for extraction and purification of
      total tanshinones from Radix Salviae Miltiorrhizae. METHODS: Using orthogonal
      design, and taking the extraction percentage of total tanshinones and tanshinone
      IIA as indexes, the extraction conditions of total tanshinones from Radix Salviae
      Miltiorrhizae and the purification conditions of total tanshinones from crude
      extract were optimized respectively. RESULTS: The optimal technical process for
      extraction of total tanshinones was as follows: added 7 volumes of 90% aqueous
      ethanol, extracted three times and each time for 1.5 hours. The optimal technical
      process for purification of total tanshinones was as follows: 15 volumes of 8%
      sodium carbonate solution, washing 5 times and each time stirring for 5 minutes.
      CONCLUSION: The content of total tanshinones in crude extract increased from
      18.23% to 57.29% by purification. The optimal technical processes for extraction
      and purification of total tanshinones are practical in industrial production.

PMID- 18619252
TI  - [Study on preparation of glycyrrhiza total flavones effective components
      sustained-release pellets and its properties].
AB  - OBJECTIVE: To prepare the glycyrrhiza total flavones effective components pellets
      by extrusion-spheronization, and to optimize the formulation of glycyrrhiza total
      flavones effective components sustained release pellets coated with mixed
      Eudragit RS 100. METHODS: The sustained-release pellets of glycyrrhiza total
      flavones were prepared by Glatt fluid bed technique. The factors influencing the
      drug release behaviors and their properties were evaluated. RESULTS: The optimal
      drug sustained-release was shown at the loading weight of copolymers of 6% and
      the plasticizer concentration of 10%. And the curves of cumulative drug release
      were fit for Peppas and Higuchi equation. CONCLUSION: The pellets show obviously
      sustained-release effect.

PMID- 18619253
TI  - [Studies on solubility enhancement of curcumin by Polyvinylpyrrolidione K30].
AB  - OBJECTIVE: To study solubility enhancement of curcumin by Polyvinylpyrrolidione
      K30 (PVP K30). METHODS: Solid dispersion systems (SDS) of curcumin in PVP K30
      were prepared at various weight ratios by co-evaporation of curcumin and PVP K30
      ethanol solution. The differential scanning calorimetry (DSC) and powder X-ray
      diffractometer method were used to describe the status of curcumin in carriers,
      the UV spectrometry method for determination of curcumin in mediums was
      established. RESULTS: The curcumin SDS was successfully prepared, the UV
      spectrometry method was accurate and reliable, and no interference occurred from
      carrier. The solubility rate in vitro of curcumin was significantly raised.
      Compared to curcumin, the solubility of curcumin in SDS increased at least 880
      folds. CONCLUSION: PVP K30 improves the solubility of curcumin well.

PMID- 18619254
TI  - [Studies on the decoction isometric from Zingiberaceae materials for medicine].
AB  - OBJECTIVE: To study the decoction isometric from Zingiberaceae materials for
      medicine. METHODS: We decocted the herb under the simulation decoction condition,
      contained the volatile oil which dissipated from the decoction and the
      concentration process, dried the broth, and computed the received rate. RESULTS:
      We Obtained the loss percentage of the volatile oil for various raw matrials for
      medicine in the decoction process, the amount of volatile oil which was contained
      in the physic liquor, and the decoction isometric dosage. CONCLUSION: It is
      suggested collecting the volatile oil while decocting the medicinal, and this
      study provids the basic data for the single herba granular formulation production
      and the marked level for the raw materials.

PMID- 18619255
TI  - [Study on transdermal absorption characteristics of brucine in vitro].
AB  - OBJECTIVE: To study the transdermal absorption characteristics of brucine in
      vitro. METHODS: The oil-water partition coefficient of brucine was measured. Drug
      permeation tests were performed through excised rat skin in improved Franz
      diffusion cell. Brucine concentration in samples was determined by HPLC. RESULTS:
      The oil-water partition coefficient of brucine was between 4.05 and 5.02 at
      different temperatures. The permeation rate of 0.5 and 1 mg/ml brucine solution
      were (1.83 +/- 0.85) and (3.74 +/- 1.54) microg/cm2 x h, respectively. The
      cumulative permeation ratio in 24 hours were (51.30 +/- 18.51)% and (50.01 +/-
      12. 80)%, respectively. CONCLUSION: The research provides experimental datas for
      the design of transdermal delivery system of brucine.

PMID- 18619256
TI  - [The summary of the clinic study of Zhi-Xin-Fang treating the heart failure
      resulting from cardiomyopathy].
AB  - OBJECTIVE: To observe the therapeutic and prognostic effects and to evaluate the
      safety of Zhi-Xin-Fang on heart failure resulting from cardiomyopathy. METHODS:
      62 patients with cardiomyopathy combined with heart failure were treated with
      standard western medical therapy as treatment group. The other 60 patients with
      the same diseases were administered with both Zhi-Xin-Fang and standard western
      medicines as control. Several parameters were observed to evaluate the effect of
      Zhi-Xin-Fang on the heart failure, containing the therapeutic effect of clinical
      symptom and physical signs, the improvement of heart function and the ultrasonic
      caridogram. We also observed the effect of Zhi-Xin-Fang to relieve the clinical
      symptom and improve the heart function and quality of life and prognosis.
      RESULTS: As the NYHA classify for heart failure, the effective rate for the
      treatment group was 95% , more effective than the control group (effective rate:
      80.65%) (P<0.05). There was significant improvement for LVEF and LVDS for both
      groups. However, the treatment group was better than the control group (P<0.05).
      The clinical symptom was significantly improved compared to the untreatment in
      both groups. The treatment group was better than the control group for effective
      rate (P<0.05) but not for the total effective rate. There was no significant
      difference for the function of liver and kidney, blood routine method,
      electrolyte compared to before for the two groups. CONCLUSION: The standard
      western medicines combined with Zhi-Xin-Fang is a good therapy for treating heart
      failure resulting from cardiomyopathy. The combined therapy can relieve the
      cinical symptom of heart failure, improve the heart function and quality of life.
      It is also safer for the patients. However, its long-term prognosis should be
      further studied in the future.

PMID- 18619257
TI  - [Study on rapid propagation of Changium smyrnioides].
AB  - OBJECTIVE: For the protection of Changium smyrnioides Wolff germ-plasm resources.
      METHODS: Rapid propagation was conducted by tissue culture. RESULTS: The best
      explants were leaves. The optimum culture medium for the induction of callus was
      MS + 2,4-D 1.0 mg/L + Kt 1.0 mg/L; that of bud was MS + 6-BA 3.0 mg/L + NAA 0.2
      mg/L; and that of root was MS + IBA 0.4 mg/L or MS + NAA 0.4 mg/L. CONCLUSION:
      Rapid propagation of Changium smyrnioides is established with tissue culture,
      which provides an effective way for the sustainable utilization.

PMID- 18619258
TI  - [Phenols in seedling cortex of Magnolia officinalis from Enshi].
AB  - OBJECTIVE: To study the phenols in Cortex of Magnolia officinalis of biernial
      seedings produced in Enshi, Hubei. METHODS: The content of magnolol and honokiol
      in cortexes were determined by HPLC. The chromatograms of 10 samples seedling
      cortexes were recorded and compared. RESULTS: The content of magnolol and
      honokiol in Cortex of Magnolia officinalis of the seedlings from Enshi was higher
      than other samples. There were ten characteristic absorption bands in the HPLC
      chromatograms, which differed from the cortex of adult trees. CONCLUSION: The
      results can be used to identify the quality of the seedlings for the breeding.

PMID- 18619259
TI  - [Content variation of saponins and flavonoids from growing and harvesting time of
      Glycyrrhiza uralensis].
AB  - OBJECTIVE: Determining and comparing the saponins and flavonoids contents in
      Glycrrrhiza uralensis Fisch to know theObjective: Determining and comparing the
      saponins and flavonoids contents in Glycyrrhiza uralensis Fisch to know the
      dynamic variation. METHODS: The contents were determined by ultraviolet
      spectrophotometry. RESULTS: Two contents had basically theMethods:The contents
      were determinedby ultraviolet spectroihotometry. Results: Two contents had
      basically the same change cultivated in Gansu and Inner Mongolia. CONCLUSION: The
      plant 3-year cultivated has the highest content. Having high con-same change
      cultivated in Gansu and Inner Mongolia. Conclusion:The plant 3-year cultivated
      has the highest content. Having high content of Saponins in August and flavonoids
      in May and October which can be used as the basis for harvesting and processing.

PMID- 18619260
TI  - [Studies on quality evaluation of Penis et Testis Cervi by Grey incidence degree
      method].
AB  - OBJECTIVE: To systematically evaluate the quality of Penis et Testis Cervi.
      METHODS: Grey model was set up by determining six main compositions contained in
      the samples. RESULTS: The quality evaluation on 9 samples by this model was as
      same as tradition and reality. CONCLUSION: Grey incidence degree method and the
      model can be used to evaluate the quality of Penis et Testis Cervi.

PMID- 18619261
TI  - [Ribosomal DNA ITS sequence of analysis of Psammosilene tunicoides from different
      populations].
AB  - OBJECTIVE: To analyze the ribosomal ITS sequence variation of Psammosilene
      tuncolides W. C. Wu et C. Y. Wu from different populations, for identifying
      different local populations. METHODS: A pair of primers of 18SP1 and 26SP2 with
      PCR technique had been applied to study the ITS sequences. RESULTS: The sequences
      of ITS1, ITS2 and 5.8S are 225-229 bp, 166-170 bp and 261-264 bp. Among 12 local
      populations, the sequence of Kunming, Lijiang, Gejiu, Heqing of Yunnan and
      Yanyuan of Sichuan showed no variation, there were 1-4 variable sites (including
      5.8S coding region) in pairwise comparison of the other 7 local populations,
      including Xuanwei, Huize, Zhongdian, Baoshan of Yunnan, Muli of Sichuan and
      Linzhi of Tibet. CONCLUSION: Comparative analysis shows that the ITS sequences of
      different local populations in the middle of Yunnan, southwest of Sichuan and
      west, northwest of Yunnan, southeast of Tibet, southwest of Sichuan have
      different fingerprint character, so the ITS sequences can be used to identify
      different local populations. The variation of ITS sequence of Psammosilene
      tunicoides is related to its geographical distribution.

PMID- 18619262
TI  - [Constituents of essential oil from different processing drynesses of Radix
      Angelicae Dahuricae].
AB  - OBJECTIVE: To analyze the constituents of essential oil from different processing
      drynesses of Radix Angelicae Dahuricae. METHODS: Water steam distillation and GC
      MS were used. Relative contents were determined by area. RESULTS: 37 compounds
      were identified. The constituents of essential oil the constituents from Radix
      Angelicae Dahuricae by insolation, drying and microwave dryness were similar, but
      one by dryness after sulfurizing and dryness after perspiring were different.
      CONCLUSION: Dryness after sulfurizing and dryness after perspiring are not fit
      for the dryness of Radix Angelicae Dahuricae.

PMID- 18619263
TI  - [Studies on morphology and histology of Pinellia pedatisecta].
AB  - OBJECTIVE: To provide evidence for identification of the morphology and histology
      of Pinellia pedatisecta Schott. METHODS: Using microscope and scanning electron
      microscope, characteristics of the Pinellia pedatisecta Schott. were studied
      comparatively. RESULTS: The surface of leaves, fruits, testa and pollen grain of
      the cultivated Pinellia pedatisecta Schott. showed different characteristics.
      CONCLUSION: The results of the study can be used for the identification of the
      Pinellia pedatisecta Schott. in Shandong.

PMID- 18619264
TI  - [Phenols from the rhizomes of Arachniodes exilis].
AB  - OBJECTIVE: To study the chemical constituents of Arachniodes exilis. METHODS: The
      methanolic extract was isolated and purified by silica gel, C18 reverse phase
      silica gel and Sepadex LH-20 gel column chromatography. The chemical structures
      were elucidated on the basis of the physicochemical properties and spectral data.
      RESULTS: Eight phenolic compounds were obtained and identified as aspidin-BB (I),
      4-methyl-2-butyl-3,5-dihydroxyphenol (II ), eriodictyol (III), epicatechin (IV),
      procyanidin B2 (V), miscathoside (VI), eriodictyol-7-O-beta-D-glucopyranuronide
      (VII), luteolin-4'-O-beta-D-glucopyranuronide (VIII), respectively. CONCLUSION:
      Compounds II-VIII are obtained from this plant for the first time.

PMID- 18619265
TI  - [Studies on chemical constituents of the seeds of Allium cepa].
AB  - OBJECTIVE: To study the chemical constituents from the seeds of Allium cepa L.,
      the constituents of the seeds of Allium cepa L. METHODS: To isolate and purify by
      silica gel, macroporous resin HP-20, Sephadex LH-20, RP-18 column. RESULTS: Seven
      compounds were isolated from the EtOH extract of the seeds of Allium cepa., their
      structures were elucidated by physico-chemical properties and spectroscopic
      analysis as tianshic acid (I), N-trans-feruloyl tyramine (II), beta-sitosterol-3
      beta-glucopyranoside-6'-palmitate (III), sitosterol (IV), daucosterol (V),
      tryptophane (VI), adenine riboside (VI). CONCLUSION: Compounds V-VIII are
      obtained from this plant for the first time, compounds I-IV are isolated from the
      genus Allium for the first time.

PMID- 18619266
TI  - [Study on flavonoiels and phenolic acids from the herb of Lygodium japonicum].
AB  - OBJECTIVE: To study the chemical constituents of the herb of Lygodium japonicum.
      METHODS: The constituents isolated by column chromatography and their structrues
      were elucidated through spectroscopic analysis. RESULTS: The compounds were
      identified as 3,4-dihydroxyl benzoic acid 4-O-beta-D-(4'-O-methyl)
      glucopyranoside (I), protocatechuic acid (II), acacetin 7-O-(6'-O-a-L
      rhamnopyranosyl)-beta-sophoroside (III), 6,8-di-glucosylapigenin (vinenin) (IV),
      tricin-7-O-beta-D-glucopyranoside (V), 2-anilino-1,4-naphthoquinone (VI).
      CONCLUSION: All these compounds are obtained from Lygodiaeae for the first time.

PMID- 18619267
TI  - [Studies on the chemical constituents of Salvia miltiorrhiz of Lijiang].
AB  - OBJECTIVE: To study chemical constituents of Salvia miltiorrhiz of Lijiang.
      METHODS: The constituents were separated and purified by column chromatography
      with silica gel. Their structures were identified on the basis of physical and
      spectral data. RESULTS: Eleven compounds were isolated and identified as: (1)
      ferlalic acid; (2) O-hydroxybenzoic acid; (3) protocatechualdehyde; (4) beta-3,4
      dihydroxyphenyl-lactic acid; (5) ursolic acid; (6) 6,7-dimethoxy-5,4'-dihydroxy
      flavonol-3-O-glucoside; (7) carnosol; (8) tanshinone II(A); (9) tanshinone I;
      (10) 5,6-dehydrosugiol; (11) crypotanshinone.

PMID- 18619268
TI  - [Studies on volatile oil from Atractylodes macrocephala with different distill
      methods].
AB  - OBJECTIVE: To study on volatice oil from Atractylodes macrosephala Koidz with
      different distill methods and find the better method. METHODS: GC-MS was used to
      analyze the chemical constituents of volatice oil from Atractylodes macrocephala
      Koidz with different distill methods. RESULTS: The extraction rates of volatice
      oil with steam distillation was 1.01%, the components of the oil were examined by
      GC-MS, 15 of the 18 were identified. The extraction rates of volatice oil with
      ultrasonic wave was 1.60%, the components examined, 20 of the 24 were identified.
      The extraction rates of volatice oil with SFE-CO2 was 2.32%, the components
      examined, 37 of the 49 were identified. Atractylon was the highest one. There
      were 12 common components in the identified ones. CONCLUSION: The components of
      volatice oil from Atractylodes macrocephala Koidz with different distill methods
      have difference but similarities, it can provide a method for Atractylodes
      macrocephala Koidz's quality control. The extraction rates is higher and the
      components are more with the method of SFE-CO2.

PMID- 18619269
TI  - [Chemical constituents study on the fruiting bodies of Lactarius rufus].
AB  - OBJECTIVE: To investigate the chemical constituents of Lactarius rufus. METHODS:
      Chemical constituents of Lactarius rufus were isolated by column chromatography.
      RESULTS: Six compounds were isolated and identified as stearic acid (1), 3beta
      hydroxyerg-osta-5,7,22-triene (2), sotolon (3), lactarorufin A (4), rufuslactone
      (5) and D-allitol (6), respectively. CONCLUSION: Compound 5 is the main
      sesquiterpenoid of Lactarius rufus and has the potential for the further
      investigation.

PMID- 18619270
TI  - [The primary evaluation of Sal-Ammoniac extract on the therapy action in mice
      bearing Lewis lung cancer].
AB  - OBJECTIVE: To evaluate the therapy action of Sal-Ammoniac extract on Lewis lung
      cancer and its toxicity to immunity. METHODS: The proliferation and cell cycle of
      Lewis lung cancer cells were determined by MTT assay and flow cytometry
      respectively. The antitumor effect of Sal-Ammoniac extract was observed by tumor
      injected subcutaneously in mice and its toxicity to immunity was examined by
      clearance rate of charcoal particles and delayed type hypersensitivity. RESULTS:
      Sal-Ammoniac extract could inhibit the proliferation of Lewis lung cancer cells
      with S cell cycle arrest in a dose-dependent manner in vitro. Sal-Ammoniac
      extract solution injected in tumor for eight days had 46.7% inhibition on Lewis
      lung cancer, if taken orally had only 15.7% inhibition on Lewis lung cancer in
      mice. Sal-Ammoniac extract solution injected subcutaneously or taken orally had
      no effect on the clearance rate of charcoal particles and delayed type
      hypersensitivity in mice. CONCLUSION: The antitumor action of Sal-Ammoniac
      extract has relation to its recipe and has no influence on immunity.

PMID- 18619271
TI  - [Protective effect of Isodon lophanthoides on acute hepatic injury induced by D
      galactosamine in rats].
AB  - OBJECTIVE: To study the protective effects of Isodon lophanthoides (ILVG) aqueous
      extract on acute hepatic injury induced by D-galactosamine (D-Gal) in rats.
      METHODS: 60 rats were divided into control group, model group, and low, middle,
      high dosage group, Bifendate group randomly. In test groups, rats received either
      ILVG aqueous extract (15, 7.5, 3.75 g/kg) or Bifendate (45 mg/kg) by gastric
      perfusion daily for 7 consecutive days. On the sixth day, D-Gal (550 mg/kg) was
      given to rats by oral administration. The levels of ALT, AST, ALP, TBA, T-Bil, TP
      and ALB in serum were analyzed. The weight of body, liver, spleen and thymus of
      each rat were measured. The hepatic glycogen content was analyzed individually.
      Liver tissue pathology was observed. RESULTS: ILVG coud decrease the ALT, AST,
      ALP, TBA and T-Bil in serum, increase TP, ALB and hepatic glycogen content and
      restrain the enlargement of liver and the shrinkage of thymus, reduce necrosis in
      pathological observation. CONCLUSION: ILVG aqueous extract possesses the effect
      on protecting on acute hepatic injury induced by D-Gal in rats, its effect is
      related to multifarious mechanism.

PMID- 18619272
TI  - [Experimental study on effect of Liuwei Dihuang Pill on HSC from mouse marrow].
AB  - OBJECTIVE: To investigate the effect of Liuwei Dihuang Pill on the number, the
      surface marker, cell cycle and colony formation of HSC from mouse marrow.
      METHODS: Old Kunming mice were randomly divided into 4 groups: the control group,
      low, middle and high dose of Liuwei Dihuang Pill group. Then we separated the HSC
      from marrow after 7 days fed with saline or Liywei Dihuang Pill respectively,
      numerated monocyte, detected the surface marker and cell cycle of the HSC by FACS
      and tested the colony forming by semisolid media culture. RESULTS: Among the four
      groups, there was no obvious difference in the number of MNC, suspended cell and
      colony. The expression of Sca-1 and CD34 increased in the low and middle dosage
      group, it meant that the number of HSC elevated by low and middle dosage
      medicine. The ability of cell proliferation was also higher in the three dosage
      groups. CONCLUSION: Liuwei Dihuang Pill activates HSC by increasing the number,
      proliferation and function of more primitive HSC.

PMID- 18619273
TI  - [Pharmacokinetics of honokiol in rat after oral administration of Cortex of
      Magnolia officinalis and its compound preparation Houpu Sanwu Decoction].
AB  - OBJECTIVE: To study pharmacokinetics of honokiol in Cortex of Magnolia
      officinalis and its compound prescription Houpu Sanwu Decoction (HPSWD) in rat,
      and discuss the change on pharmacokinetic process affected by other components.
      METHODS: The rats were divided into two groups, one was supplied with HPSWD and
      the other was administrated with Cortex of Magnolia officinalis. Concentrations
      of honokiol in rat plasma were then determined using HPLC method and main
      pharmacokinetic parameters were estimated. RESULTS: The plasma concentrations of
      honokiol of both groups were conformed to the two-compartment model with first
      order absorption. There existed significant differences in AUC, C(max), T(max),
      CL/F among Cortex of Magnolia officinalis and HPSWD. CONCLUSION: The results
      indicate that Rhubarb and Immature Orange Fruit in HPSWD can influence the
      asorption, distribution and elimination of honokiol.

PMID- 18619274
TI  - [Establishing and identifying insulin resistance 3T3-L1 adipocytes cell model].
AB  - OBJECTIVE: To establish insulin-resistant 3T3-L1 adipocytes cell model. METHODS:
      3T3-L1 preadipocytes were cultured and induced to differentation. We established
      insulin resistant 3T3-L1 induced by dexamethasone and determined the change of
      glucose concentration in cell culture. RESULTS: In high glucose DMEM culture
      media, the glusose concentration significantly decreased. Achieved the peak of
      insulin-resisitant at the 96th hour induced by dexamethasone, and at this time
      compared with the blank the mRNA expression of Resistin of the model step up
      about three times. CONCLUSION: 3T3-L1 adipocyte exposed to 1 micromol/L
      dexamethasone for 24 hours are able to induce a state of insulin resistance which
      can be maintained for 216 hours.

PMID- 18619275
TI  - [Structural analysis and anti-tumor activity in vivo of polysaccharide APS-2a
      from Angelica sinensis].
AB  - The polysaccharide APS-2a was isolated from Angelica sinensis (Oliv.) Diels
      through water extraction, deprotein, ethanol precipitation and DEAE-sephades A-25
      column chromatography respectively,and was further purified by Sephacryl S-400
      and Sephadex G-100 column chromatography. The phenol-sulfuric acid assay and
      Bradford method were used to determine the contents of carbohydrate and protein,
      respectively. The molecular weight was carried out with high-performance size
      exclusion chromatography (HPSEC) combined with a differential refractometer
      detector. The monosaccharide compositions were determined by gas chromatography
      after complete hydrolysis with acid. The models of mice transplanted sarcoma S
      180 were used to study the anti-tumor effects in vivo. Thymus indexes, spleen
      indexes were determined. The HPSEC result showed the APS-2a was a single
      homogeneous component and its weight average molecular weight was 7.4 x 10(5) Da.
      The monosaccharide composition of APS-2a was glucose, galactose, arabinose,
      rhamnose, galcturonic acid. Furthermore, APS-2a (20.50 mg/kg) could inhibit the
      proliferation of tumor cells in mice transplanted S-180. The thymus indexes and
      spleen indexes in the groups treated with APS-2a were higher than control group.

PMID- 18619276
TI  - [Study on antitumor activity of extract from roots of Gossampinus malabaria].
AB  - OBJECTIVE: To study the antitumor activity of extract (Y2) from the roots of
      Gossampinus malabaria (L.) Merr. METHODS: Based on the inhibitory effects of Y2
      on FGC-85 in vitro, life-prolonging effects of Y2 on mice transplanted with
      ascites sarcoma-180 (S-180) and antitumor activity of Y2 on mice transplanted
      with U14 were investigated in vivo. RESULTS: The growth of S-180 in mice was
      significantly inhibited by Y2. The inhibitory growth effect was dosage-dependent.
      Y2 could significantly prolong the survival time of mice transplanted with S-180.
      The inhibition rate of Y2 on the growth of U14 in mice was higher than 90% under
      high, medium and low dosage. CONCLUSION: Y2 has distinct antitumor activity.

PMID- 18619277
TI  - [Studies on the antioxidative activity of polysaccharides from radix
      Saposhnikoviae].
AB  - OBJECTIVE: To research the antioxidant activity of polysaccharides from
      Saposhnikovia divaricata (Turez.) Schischk. METHOD: Polysaccharides from
      Saposhnikovia divaricata (Turez.) Schischk were obtained through hot water
      extracting and ethanol precipitating method. Using CTAB as precipitant,
      Saposhnikovia polysaccharide was separated into acid Saposhnikovia polysaccharide
      (A-SPS) and neutral Saposhnikovia polysaccharide (N-SPS). The total reducing
      power, scavenging effect to superoixide anion (O2-*), hydroxyl radical (*OH), 1,
      1-diphenyl-2-picrylhydrazyl radical (DPPH*) and inhibiting effect to lipid
      peroxidation induced by Fe2+ of different Saposhnikovia polysaccharides were
      measured in vitro chemical simulated systems for evaluating their antioxidant
      activity. RESULTS: Saposhnikovia polysaccharides had some functions of scavenging
      free radicals and inhibiting lipid peroxidation, and scavenging effects on DPPH*
      and OH* were especially significant. A-SPS had better effect among different
      Saposhnikovia polysaccharides, and the scavenging rate of DPPH* and OH* could
      approach to 70% when the experimental concentration was 8 mg/ml . CONCLUSION: A
      SPS, potential main active ingredient of Saposhnikovia polysaccharide, has strong
      antioxidant activity and can be applied as a potential natural antioxidant in
      food and medicine industry.

PMID- 18619278
TI  - [Effects of Dioscorea septemloba on the biomechanical and bone histomorphometric
      parameters of femur in the ovariectomized rats].
AB  - OBJECTIVE: To investigate the effects of the decoction of Rhizoma Dioscoreae
      septemlobae (RD) on the biomechanical and bone histomorphometric parameters of
      femur in the ovariectomized rats. METHODS: 25 female Wistar rats without
      pregnancy and deliver were divided into 5 groups randomly: sham (sham-operation),
      ovariectomy (OVX), OVX + high dosage RD (4 g/kg x d), OVX + middle dosage RD (2
      g/kg x d) and OVX + low dosage RD (1 g/kg x d), n = 5 in every group. After
      intragastric administration 12-week period continuously, the biomechanical and
      the bone histomorphometric parameters of the femur of the rats in every group
      were determined, respectively, including percentage of trabecular bone volume
      (TBV%), percentage of trabecular osteoid (TOS%), mean osteoid width (MOSW),
      percentage of mineralizing surface (MdS%), percentage of double mineralizing
      surface (DMds%), percentage of DMds/MdS (%), percentage of travecular formation
      surface (TFS%), percentage of trabecular resorption surface (TRS%), mineral
      apposition rate (MAR), mineralizing lag time (MLT). RESULTS: The maximum loading,
      deflection, the maximum strain of the femur in the OVX group was 125.78 +/- 15.48
      (N), 1.87 +/- 0.22 (mm), 9.34 +/- 1.10 (%), it was significantly lower than that
      in the sham group ( P< 0.05, P < 0.01), respectively. The maximum loading and
      maximum stress was increased in different extent in the every dose group of OVX +
      RD, respectively. TBV% of femur was significantily lower in the OVX group than
      that in the sham group (P < 0.01). The MdS%, DMds%, DMds/MdS (%), TOS%, MOSW,
      TRS%, MAR was significantly higher in the OVX group than that in the sham group,
      respectively (P < 0.01). In the RA high and middle dosage group, the TBV% of
      femur was significantly higher than that in the model group (P < 0.05), and the
      MdS%, DMds%, DMds/MdS (%), TRS%, TOS%, MOSW, MAR was significantly lower than
      that in the model group, respectively (P < 0.05), and MLT was decurtated slightly
      (P > 0.05). CONCLUSION: The decoction of RD can decline the bone turnover and the
      loss of bone of femur in the ovariectomized rats.

PMID- 18619279
TI  - [Study on the release of oleanolic acid loaded nanocapsules in vitro].
AB  - OBJECTIVE: To study the release of oleanolic acid loaded nanocapsules in vitro.
      METHODS: The rules of drug release in vitro from oleanolic acid loaded
      nanocapsules were observed by dynamic penetration system and HPLC. RESULTS: The
      profile curve of oleanolic acid loaded nanocapsules was fit for the Weibull
      equation. The release t(1/2) of oleanolic acid loaded nanocapsules was about 6.7
      times as that of original oleanolic acid. CONCLUSION: Oleanolic acid loaded
      nanocapsules have obviously sustained effect.

PMID- 18619280
TI  - [Optimization of ligustrazine phosphate thermosensitive gel formulation by
      central composite design-response surface methodology].
AB  - OBJECTIVE: To optimize the formulation of ligustrazine phosphate thermosensitive
      gel by the central composite design-response surface methodology (RSM plus CCD).
      METHODS: In the formulation design using RSM plus CCD, independent variables were
      the amounts of poloxamer 407 and poloxamer 188, and gel temperature was dependent
      variable. Multilinear and quadratic models were used to estimate the relationship
      between the dependent and the independent variables, select the optimal
      formulations and validate. RESULTS: The quantitative relationships between two
      factors and evaluation index were characterized, quadratic model had better
      prediction capability than multilinear model. CONCLUSION: Quadratic model is
      performed in the optimization of formulation due to the statistical confidence.
      The optimization of ligustrazine phosphate thermosensitive gel formulation can be
      achieved by the central composite design and response surface methodology.

PMID- 18619281
TI  - [Improvement of synthesis of quercetin and genistein sulfates and identification
      by HPLC-MS].
AB  - OBJECTIVE: To improve synthesis of quercetin and genistein sulfates. METHODS:
      Quercetin and genistein were esterified with concentrated sulfuric acid for 3
      hours in ice and esterfication was terminated by neutralization with 6N NaOH.
      Derivatives were identified by HPLC-APCI-MS. RESULTS: Quercetin and genistein
      derivatives were only one compound of monosulfate. CONCLUSION: The improvement of
      synthesis of quercetin and genistein sulfates is a convenient method for
      obtaining soluble derivatives of the flavonoids.

PMID- 18619282
TI  - [The studies on the Ku Huang granula technology].
AB  - OBJECTIVE: To determine the optimum technology of the Ku Huang granula. METHODS:
      Making Emodin and Chrysophanol for index, using HPLC, extracturm softening point
      data and orthogonal design experiment to research the preparatory technology of
      the Ku Huang granula to screen the optimum technology. RESULTS: The Ku Huang
      granula was pelletized at 100% dextrin, 170 degrees C- 175 degrees C spray drying
      and at the conditions of 75% ethylalcohol, 85 degrees C, 4 Hz, 3 hours fluidizing
      pelletization. CONCLUSION: The optimum condition is reasonable.

PMID- 18619283
TI  - [Terahertz spectroscopic investigation of crystalline beta-D-galactopyranose].
AB  - In order to deeply understand the spectral characteristics of beta-D
      galactopyranose in the terahertz region, terahertz time-domain spectroscopy was
      used to measure the absorption coefficient and refractive index in the frequency
      range 0.3-3.0 THz at room temperature, and Fourier transform infrared
      spectroscopy was also used to obtain the absorption spectrum between 1.5 and 19.5
      THz. In parallel with the experimental study, the 6-311+G * * basis set and
      density functional theory(DFT) were applied to obtain the structure and
      vibrational frequencies of the isolated beta-D-galactopyranose molecule at in
      phase. The observed vibrational spectra were assigned according to the DFT
      calculations. Results show that the theoretical calculations are in good
      agreement with the experimental data except somewhat blue shifts due to the
      intermolecular interactions. The observed resonances at the high frequency above
      6 THz originate from distinct intra-molecular vibrational modes, while at the low
      frequency below 6 THz the observed resonances are dominated by vibrations of
      hydrogen bonds between the molecules or phonon modes. The comparison of
      experimental and theoretical studies shows that far-infrared absorption features
      are highly sensitive to the structure and spatial arrangement of molecules.

PMID- 18619284
TI  - [Line intensities of upsilon2 perpendicular band and the change of intensities
      with temperature for H12C14N].
AB  - The total internal partition sums (TIPS) were calculated for H12C14N with the
      product approximation. For rotational partition sums Q(rot), the centrifugal
      distortion corrections were taken into account. The calculation method for the
      vibrational partition sums Q(vib) is the harmonic oscillator approximation. The
      line intensities of upsilon2 perpendicular band (0110-0000 transition) of H12C14N
      were calculated at normal temperatures and several high temperatures by using the
      calculated partition functions and experimental transition moment squared and
      Herman-Waills factor coefficients. Results showed that our line intensities data
      at 296 and 3 000 K are in excellent agreement with the data in HITRAN, which
      provide a strong support for the calculations of partition function and line
      intensity at high temperature. Thereby, the line intensities and spectral
      simulations of upsilon2 perpendicular band at the higher temperatures 4 000 and 5
      000 K were presented and the chang in line intensities with the temperature was
      discussed. For those transitions corresponding to rotational quantum number J >
      or = 32 (including P, Q and R branch), the line intensities increase when
      temperature gradually increase from 296 K. The line intensities are up to the
      largest at around 1000 K and then weaken rapidly. For J < 32 (also including P, Q
      and R branch), the line intensities are the largest at 296 K and then weaken
      rapidly as temperature gradually increase.

PMID- 18619285
TI  - [Emission spectroscopy diagnostics of plasma electron temperature].
AB  - Electron temperature is one of the important parameters of plasma. It is very
      difficult to measure the electron temperature exactly and instantly owing to its
      complexity during discharge. As a plasma diagnostics technique, emission
      spectroscopy is widely applied in the study and diagnosis of any kind of plasma,
      because of its simple instrument system, noninterference of measurement, high
      sensitivity and fast responsibility. In the present paper, some methods for
      plasma electron temperature diagnosis, such as two lines method, multiline slope
      method, isoelectronic line method, Saha-Boltzmann equation, absolute intensity
      method, were introduced. And the applications of these methods were reviewed to
      provide reference for choosing appropriate methods in practice.

PMID- 18619286
TI  - [Investigation on the delay time of coal experiment by laser-induced breakdown
      spectroscopy].
AB  - Laser-induced breakdown spectroscopy is a new technology of elementary analysis,
      and it will be used in coal analysis. The delay time of signal is an important
      parameter of spectral analysis. A LIBS system was set up and three kinds of coal
      (Jiangxipingxiang coal, Shanxixishan coal and Guizhoupingzhai coal) were chosen
      for this investigation. The spectra in the range of 240 to 250 nm and 275 to 290
      nm of the each three coal samples are shown and they record several spectral
      lines of components such as C, Mg and Si according to the NIST database. The
      temporal evolution of SNR of spectral line was obtained, and the value of SNR
      increased with the time delay, then decayed. The temporal evolution of SNR was
      different as the coal, element and spectral line differs. Finally, optimum delay
      time of each spectral lines of elements in the coal samples was calculated
      according to the biggest value of signal-to-noise ratio, and the relation between
      the characteristic of coal, element, spectral line and the op timum delay time
      was analyzed.

PMID- 18619287
TI  - [Investigation on performance enhancement of bulk heterojunction organic solar
      cells].
AB  - Four organic solar cells with the different structures were fabricated. The
      structures are Device1 ITO/LiF/PEDOT: PSS/MEH-PPV/C60/Al, Device 2 ITO/PEDOT :
      PSS/MEH-PPV/C60/Al, Device 3 ITO/LiF/PEDOT : PSS/MEH-PPV : C60/C60/Al and Device
      4 ITO/PEDOT : PSS/MEH-PPV : C60/C60/Al. Then we compared the current-voltage (I
      V) characteristics of these devices and found that the insertion of a thin LiF
      layer between the ITO electrode and the PEDOT : PSS layer resulted in much
      improved device performance. The short-circuit current density (J(sc)) and fill
      factor (FF) of Device 1 were enhanced by 74% and 31%, respectively as compared to
      those of Device 2. The short-circuit current density (J(sc)) of Device 3 is about
      1.4 times as large as that of Device 4. The increased solar cell performance
      mostly can be attributed to the fact that the hole transport to the anode can be
      effectively suppressed by a thin LiF layer, and the thin LiF layer between the
      ITO electrode and the PEDOT: PSS layer can form better interface properties.
      Hence, such change in structure of solar cells improves the performance of the
      organic solar cells effectively.

PMID- 18619288
TI  - [Spectral characteristics of different discharge modes in air dielectric barrier
      discharge].
AB  - The electron energy in the transition from streamer discharge to glow-like
      discharge in dielectric barrier discharge in air was investigated by using
      emission spectra. The vibrational temperature was measured with the N2 second
      positive band (C3II(u) --> B3II(g)) of the emission spectrum. The average
      electron energy was investigated from the relative intensity of the nitrogen
      molecular ion line at 391.4 nm and the nitrogen molecular line at 337.1 nm. It
      was found that the vibrational temperature and the relative intensity of nitrogen
      molecular ion line at 391.4 nm increased abruptly in the transition from streamer
      discharge to glow-like discharge. It was also found that the pressure for the
      transition pressure from streamer discharge to glow-like discharge changed with
      different gap distances, but the product of the transition pressure and gas gap
      width remained constant.

PMID- 18619289
TI  - [Influence of nitrogen doping on electron structure and optical properties of
      amorphous carbon thin films].
AB  - Nitrogen doped amorphous carbon (a-C : N) thin films were prepared by DC
      magnetron sputtering. The films were investigated by AES, UV-Vis and
      ellipsometer. A parameter 'D' defined as the distance between the maximum of
      positive going excursion and the minimum of negative going excursion was
      calculated in the derivative AES spectra. The values of 'D' were used to
      calculate the percentage of sp2 hybrid bonds. The optical transmission and the
      optical band gap of the films were characterized by an UV-Vis spectrophotometer.
      The results showed that the optical band gap decreased and then increased with
      the increase of N2 gas source. The transmission and refractive index changed in
      reverse order. It was demonstrated that the thin film with low percentage of
      nitrogen was beneficial to the formation of sp3 hybrid bonds and caused the
      optical band gap of the thin film to increase. As a result, the thin film should
      be prepared under low percentage of nitrogen pressure to ensure that it possesses
      fine optical properties.

PMID- 18619290
TI  - [Study of photochemically converted PPV films].
AB  - The authors present photoluminescence (PL) and Raman spectra of PPV converted in
      vacuum by ultraviolet(UV) irradiation which indicate partial conjugation similar
      to thermally converted poly(p-phenylene vinylene) (PPV). The authors have
      fabricated OLEDs based on photo-converted PPV. Though the electroluminescence
      (EL) spectra are poor, doped PPV-based OLED devices are achieved.

PMID- 18619291
TI  - [Effects of Sb3+ on the luminescent properties of Tb3+ doped silicate glass].
AB  - The Sb(3+)-doped silicate glasses, Tb(3+)-doped silicate glasses, and Sb3+ and
      Tb3+ co-doped silicate glasses were synthesized by high-temperature melting
      method, and their spectral properties were analyzed. The effects of Sb2O3 added
      as a fining agent on the luminescent properties of Tb(3+)-doped silicate glasses
      were studied with excitation spectra, emission spectra and decay time. The
      results show that there is energy transfer from Sb3+ ions to Tb3+ ions in the
      Sb3+ and Tb3+ co-doped silicate glasses under UV excitation, but the energy
      transfer efficiency between them is quite low. The energy transfer takes place
      between the 3P1 energy level of Sb3+ ions and the 5D3 energy level of Tb3+ ions
      in the Sb3+ and Tb3+ co-doped silicate glasses, and the way of the energy
      transfer from Sb3+ ions to Tb3+ ions is nonradiative energy resonance transfer.
      Meanwhile, introducing Sb2O3 used as a fining agent will reduce the excitation
      intensity of Tb3+ ions in the silicate glasses in the overlap excitation region
      of both Sb3+ ions and Tb3+ ions, which corresponds to the region from 200 to 350
      nm. The reduction in the excitation intensity of Tb3+ ions caused by introducing
      Sb3+ ions is so evident that it can not be compensated by the energy transfer
      from Sb3+ ions to Tb3+ ions. Therefore, the negative effects of Sb3+ ions on the
      luminescent properties of Tb3+ ions in silicate glasses should be measured when
      Sb2 O3 is planned to be used as a fining agent in Tb(3+)-doped silicate glasses.

PMID- 18619292
TI  - [White organic light emitting device with dyestuff DCJTB blended in polymer].
AB  - The Alq3 and DCJTB were blended with poly (N-vinylcarbazole) (PVK) in different
      weight ratios and spin coated into films. Multilayer devices with the light
      emitting layer PVK : Alq3 : DCJTB were fabricated, and their structure was ITO/
      PVK : Alq3 : DCJTB/ BCP/Alq3/LiF/Al in which BCP and Alq3 were employed as the
      hole-blocking and electron-transporting layers respectively, PVK is the blue
      light-emitting as well as hole-transporting layer. The mass proportion of PVK
      relative to Alq3 was tuned while the quality ratio of PVK to DCJTB remained (100
      : 1). Finally, fairly pure and stabile white emission was achieved when PVK :
      Alq3 : DCJTB was 100 : 5 : 1. The CIE coordinate was (0.33, 0.36) at 14 V, which
      is very stable at various biases (10-14 V).

PMID- 18619293
TI  - [Characteristic of optical emission spectrum in electron-assisted chemical vapor
      deposition of diamond].
AB  - The optical emission process of atomic hydrogen (Halpha, Hbeta, Hgamma), atomic
      carbon C(2p3s2p2 : lambda = 165.7 nm) and radical CH(A2delta --> X2II: lambda =
      420-440 nm) in diamond film growth by electron-assisted chemical vapor deposition
      (EACVD) from a gas mixture of CH4 and H2 was studied by using Monte-Carlo
      simulation. The variation of the emission lines with gas pressure (0.1-12.5 kPa)
      of different substrate temperatures (573-1 173 K) was investigated. And the
      results show that at different substrate temperatures the intensity of all the
      emission lines increase with increasing gas pressure at first, whereas decreased
      afterward. Furthermore, the emission lines intensity decreases with increasing
      substrate temperature at a relative low gas pressure, while increases with
      increasing substrate temperature at the higher gas pressure.

PMID- 18619294
TI  - [Characterization and photoluminescence properties of an azomethin-zinc complex].
AB  - A Schiff base organic metal complex, Bis(salicylidene)-1,2-phenylenediam-ine
      Zinc(II) with high purity, was synthesized and purified by vacuum sublimation.
      Its structure, thermal stability and energy band structure were investigated by
      element analysis, FTIR spectra, TG-DTA curve, UV-Vis absorption spectra,
      fluorescece emission spectra and PL spectra. Experimental results showed that the
      complex is a thermally stable, polycrystalline material, with glass temperature
      and decomposition temperature being 183 and 449 degrees C, respectively. In its
      infrared spectrum, a high intensity band was at about 1 385 cm(-1). This band was
      typical of the conjugated C=N stretching vibration, which shifted to higher
      frequency in relation to the free ligand of salicylaldehyde with 1,2
      phenylenediamine. The new bnd at 529 cm(-1) was assigned to Zn-O stretching
      vibration. Its UV absorption bands were at about 297 and 406 nm, and its
      tetrahydrofuran solution emitted intensive blue-green fluorescence at the peak
      wavelength of 508 nm. The absorption band at about 406 nm can be assigned to the
      intrinsic absorption of C=N. Its optical gap was about 2.62 eV, which was
      determined by the intrinsic absorption band edge of the complex in
      tetrahydrofuran solution. Under UV excitation at 365 nm, the complex in film
      emitted yellow-green fluorescence with the maximum emission peak at 562 nm and a
      full-width at half-maximum of 48.5 nm in PL spectra. Finally, yellow organic
      light-emitting devices using this complex as the emissive layer were fabricated
      and investigated.

PMID- 18619295
TI  - [Initial study of a new method for measuring the temperature of hot gas by FTIR
      spectrometry].
AB  - The present paper analyzed the molecular spectra theory detailedly and summarized
      the factors affecting the structure and intensity-distribution of molecular
      rotation-vibration spectra. The authors knew that every spectral line's relative
      intensity is only related to external temperature. According to this conclusion.
      The authors showed a new method for measuring the temperature of hot gas by FTIR
      spectrometry. The authors established a database for measuring the temperature
      database using the database of HITRAN. The authors calibrated and validated the
      database using four experimental spectral data at different temperatures. After
      calibration, the result was very good. Compared with molecular rotation-vibration
      emission spectra method and maximum spectral line intensity method, this method
      has many advantages: simple physical-contents, easy calculation (done by a C
      program), high precision etc. It was a simple and applied method.

PMID- 18619296
TI  - [Effect of powder's particle size on the quantitative prediction of volatile oil
      content in Zanthoxylum bungeagum by NIR technique].
AB  - The traditional chemical methods to measure the volatile oil content of
      zanthoxylum bungeagum encounter some problems such as long time and low
      efficiency, so it is difficult to achieve rapid detection. One hundred forty-one
      samples including 74 zanthoxylum bungeagum maxim and 67 zanthoxylum schinifolium
      Sieb. et zucc were collected, from many provinces in China such as Shan Xi, Si
      Chuan, Gan Su, Chong Qing, Yun Nan, etc. Each sample was crushed and sorted to 8
      kinds of powder samples according to the particle size of 120-mesh, 100-mesh, 80
      mesh, 60-mesh, 40-mesh, 20-mesh, 10-mesh, respectively, including the material
      retained by the 10-mesh sieve. Then, each powder sample was labeled by one of the
      following serial numbers: 120, 100, 080, 060, 040, 020, 010 and 000. For each
      sample, the NIR spectra of 8 different kinds of particle size powders were
      measured using a Bruker MATRIX-I FT-NIR spectrometer. Then, the 8 different kinds
      of particle size powders of each sample were mixed uniformly. The volatile oil
      content was measured in each sample according to the distillation stipulated by
      the Forestry Standard of PRC-Quality Classify of Prickly Ash (LY/T 1652-2005).
      Based on near infrared spectroscopy technique and partial least squares (PLS), 8
      calibration models of predicting volatile oil content were established by 141
      powder samples with 8 different kinds of particle size. Experiments indicatd that
      the model was the best with the powder's particle size of 40-mesh and the
      determination coefficient (r2(141)) and the root mean square error of cross
      validation (RMSECV141) were 0.9364 and 0.421, respectively. The model was
      established by the calibration set with 105 samples with particle size of 40
      mesh. Applying the model to the test set with 36 samples, the determination
      coefficient (r2(36)), the root mean square error of prediction (RMSEP36), the
      relative standard deviation (RSD36), and the ratio of prediction to deviation
      (RPD36) were 0.9233, 0.452, 11.66%, and 3.624, respectively. The model, based on
      the same sample set but optimized by OPUS 5.0, was developed by spectral data
      pretreatment of the Mean Centering+Vector Normalization in the spectral region of
      6 100.1-5 774.2 cm(-1) and 4 601.6-4 424.2 cm(-1). Using the model to predict the
      test set, r2(36), RMSEP36, RSD36, and RPD36 were 0.9862, 0.192, 4.95%, and 8.517,
      respectively. The results showed that the model built by samples passed through
      40-mesh screen was the best and rapid detection of volatile oil content in
      zanthoxylum bungeagum by NIR was feasible and efficient.

PMID- 18619297
TI  - [Multi-layer perceptron neural network based algorithm for simultaneous
      retrieving temperature and emissivity from hyperspectral FTIR data].
AB  - The present paper firstly points out the defect of typical temperature and
      emissivity separation algorithms when dealing with hyperspectral FTIR data: the
      conventional temperature and emissivity algorithms can not reproduce correct
      emissivity value when the difference between the ground-leaving radiance and
      object's blackbody radiation at its true temperature and the instrument random
      noise are on the same order, and this phenomenon is very prone to occur rence
      near 714 and 1 250 cm(-1) in the field measurements. In order to settle this
      defect, a three-layer perceptron neural network has been introduced into the
      simultaneous inversion of temperature and emissivity from hyperspectral FTIR
      data. The soil emissivity spectra from the ASTER spectral library were used to
      produce the training data, the soil emissivity spectra from the MODIS spectral
      library were used to produce the test data, and the result of network test shows
      the MLP is robust. Meanwhile, the ISSTES algorithm was used to retrieve the
      temperature and emissivity form the test data. By comparing the results of MLP
      and ISSTES, we found the MLP can overcome the disadvantage of typical temperature
      and emisivity separation, although the rmse of derived emissivity using MLP is
      lower than the ISSTES as a whole. Hence, the MLP can be regarded as a beneficial
      complementarity of the typical temperature and emissivity separation.

PMID- 18619298
TI  - [GC-FTIR analysis of structural isomers from hydrogenation products of p
      phenylphenol].
AB  - The hydrogenation of p-phenylphenol is a consecutive and parallel complex
      reaction. Owing to the difference in the hydrogenation ability of the two benzene
      rings in pphenylphenol, the hydrogenation products contained several structural
      isomers, which can not be identified by normal analytical method. However, the
      reaction mixture was effectively separated and identified by GC-FTIR technique.
      According to the characteristic wave numbers of benzene ring substituted at
      different positions, the main product was confirmed to be p-cyclohexylphenol, and
      the two typical by-products were p-phenylcyclohexanol and p
      cyclohexylcyclohexanol, respectively. Each product has several stereo-isomers. GC
      MS, melting point measurement and NMR proved the accuracy of GC-FTIR results,
      indicating that GC-IR is an useful and rapid method for analyzing structural
      isomers of organic compounds.

PMID- 18619299
TI  - [Study on spectroscopic properties of CuO nanoparticles].
AB  - The precursor Cu2 (NO3)(OH)3 was synthesized by homogeneous precipitation
      processing in ethanol-water(phi, 1 : 1) mixed solvent system using (CH2)6N4 as
      host-precipitates. CuO nanoparticles were prepared by heating Cu2 (NO3)(OH)3 at
      different temperatures. XRD, FTIR, XPS, FT-Raman and UV-Vis absorption spectra
      techniques were applied to investigated spectrum properties of CuO nanoparticles.
      All of the obtained samples were indicated to be monoclinic CuO under XRD
      measurement. Consistent with the XRD results, the XPS method also revealed that
      the atomic ratio of Cu to O in our samples was 1 : 1. With the increase in the
      calcinations temperature, the crystal of CuO grew up, the FTIR patterns revealed
      that the absorption of Cu-O and -OH bond in CuO nanoparticles blue-shifted and
      red-shifted at the same time, XPS spectrum indicated that the content of surface
      oxygen decreased, and the FT-Raman spectrum showed that the Raman scattering peak
      broadened with the decrease in the nano-CuO diameter; UV-Vis adsorption
      spectroscopy revealed that CuO has a wide adsorption peak at -350 nm, and the
      absorption edge blue-shifted with the size decreasing.

PMID- 18619300
TI  - [Discrimination of wood biological decay by NIR and partial least squares
      discriminant analysis (PLS-DA)].
AB  - Extensive research has demonstrated that near infrared spectroscopy (NIR) and
      partial least squares discriminant analysis (PLS-DA) can be used to rapidly
      discriminate or detect a wide variety of food, medicine and agricultural
      products. The use of NIR coupled with PLS-DA to detect wood biological decay was
      investigated in the present paper. The results showed that the correlation
      between the predicted category variable of calibration and validation and the
      measured category variable is significant with a correlation coefficient (r) over
      0.94 and low SEC and SEP (< 0.17); the discriminant accuracy for the non-decay,
      white-rot and brown-rot decay samples are 100% (deviation < 0.5) by the PLS-DA
      model based on the test set of samples; the discriminant accuracy by PLS-DA model
      is better than that by SIMCA model. It's suggested that NIR spectroscopy coupled
      with PLS-DA could be used to rapidly detect wood biological decay.

PMID- 18619301
TI  - [Research on the soluble solids content of pear internal quality index by near
      infrared diffuse reflectance spectroscopy].
AB  - The objectives of the present study were to establish the relationships between
      the near-infrared diffuse reflectance (NIR) spectra and the soluble solids
      content (SSC) of internal quality index of pear fruit, and to evaluate the value
      of NIR spectrometry in measuring the SSC of internal quality index of pear fruit.
      NIR spectroscopy in the 350-1 800 nm range was used to analyze the SSC of
      internal quality index of pear fruit with multi-linear regression (MLR),
      principal component regression (PCR) and partial least square (PLS) regression.
      Meanwhile, the best combinations of different positions at pear fruit, the
      logarithms of the reflectance reciprocal log(1/R), its first derivative D1
      log(1/R) and second derivative D2 log(1/R) were investigated. The best prediction
      results, based on the comparative analysis, were obtained with the PLS model and
      D1 log(1/R) at equatorial position of pear fruit. The results show that the
      predictions with PLS models, based on D1 log(1/R) at equatorial position of pear
      fruit, are correlation coefficients (R(p)) of 0.851 7 and root mean standard
      error of prediction (RMSEP) of 0.879 3 for SSC. The preliminary research on the
      built models indicates that NIR spectroscopy could provide an accurate, reliable
      and nondestructive method for assessing the SSC of internal quality index of pear
      fruit.

PMID- 18619302
TI  - [Research on infrared safety protection system for machine tool].
AB  - In order to ensure personal safety and prevent injury accident in machine tool
      operation, an infrared machine tool safety system was designed with infrared
      transmitting-receiving module, memory self-locked relay and voice recording
      playing module. When the operator does not enter the danger area, the system has
      no response. Once the operator's whole or part of body enters the danger area and
      shades the infrared beam, the system will alarm and output an control signal to
      the machine tool executive element, and at the same time, the system makes the
      machine tool emergency stop to prevent equipment damaged and person injured. The
      system has a module framework, and has many advantages including safety,
      reliability, common use, circuit simplicity, maintenance convenience, low power
      consumption, low costs, working stability, easy debugging, vibration resistance
      and interference resistance. It is suitable for being installed and used in
      different machine tools such as punch machine, pour plastic machine, digital
      control machine, armor plate cutting machine, pipe bending machine, oil pressure
      machine etc.

PMID- 18619303
TI  - [Application of infrared spectroscopy technique to discrimination of alcoholic
      beverages].
AB  - Infrared spectroscopy technique is a rapid for the discrimination of food
      samples, and is widely used to detect and discriminate various beverages. This
      paper presents the advantages and disadvantages of techniques that have been used
      to discriminate alcoholic beverages, and the discriminating procedure with
      infrared spectroscopy technique. Applications of infrared spectroscopy technique
      to wine, whiskey, Japanese sake and Chinese rice wine etc. is presented too.
      Finally, problems in applications are analyzed, and the application of infrared
      spectroscopy technique to the discrimination of our traditional alcoholic
      beverages is prospected.

PMID- 18619304
TI  - [In-site total N content prediction of soil with Vis/NIR spectroscopy].
AB  - The Vis/NIR spectroscopy as an efficient tool to predict within-filed soil
      properties is significantly valuable when establishing agricultural field trials
      and in precision farming. The object of the study was to investigate the
      feasibility and possibility of using transformed in-site spectra by relative
      transformation method (RTM) to prediction soil properties. One hundred and three
      samples of paddy and fluvo-aquic soil in central china were collected. The in
      site moisture (R(w)) and dried (R(d)) Vis/NIR spectra were measured by ASD field
      handHeld analyzer. The spectral characteristics of two kind soils were analyzed
      comparatively. The Rw spectra were transformed by RTM into R(n), which were of
      similar information content and charatistics with R(d). The first derivatives of
      three spectra revealed that the method could reduce the water disturb on and
      noise in R(w) Vis/NIR spectrum. The PLS regession model was applied to predict
      total nitrogen (TN) respectively using R(w), R(d) and R(n) as predictor. The
      models with Rw predicted TN respectively of paddy, fluvo-aquic and all samples
      with poor adjusted r2 (< 0.5), while R(d) with good adjusted r2 0.70, 0.88 and
      0.71 and R(n) 0.53, 0.62 and 0.64. The result showed that the RTM was efficient
      to enhance analysis and prediction of soil properties using Vis/NIR spectrum
      measured on the spot. The combination of PLS and RTM could help implemention of
      real-time analyzing soil properties using Vis/NIR spectrum.

PMID- 18619305
TI  - [Fast detection of white vinegar varieties and pH by Vis/NIR spectroscopy].
AB  - White vinegar is a condiment indispensable in our life, but our understanding of
      the white vinegar and evaluation of its quality and function has been gained
      through routine chemical and physical analysis. It is called for to develop more
      time- and cost-efficient methodologies for white vinegar detection. Visible and
      near infrared spectroscopy (Vis/NIR) is a nondestructive, fast and accurate
      technique for the measurement of chemical components based on overtone and
      combination bands of specific functional groups. Vis/NIR transmittance
      spectroscopy and chemometrics methods were utilized in classification and pH
      mensuration of white vinegar in the present study. First, the spectral curves of
      white vinegar were obtained by handheld Vis/NIR spectroradiometer, then principal
      component analysis (PCA) was used to process the spectral data after
      pretreatment. Five principal components (PCs) were selected based on accumulative
      reliabilities (AR), and these selected PCs would be taken as the inputs of the
      three-layer back-propagation artificial neural network (BP-ANN). A total of 240
      white vinegar samples were divided into calibration set and validation set
      randomly, the calibration set had 180 samples with 60 samples of each variety,
      and the validation set had 60 samples with 20 samples of each variety. The BP-ANN
      was trained using samples in calibration set, the optimal three-layer BP-ANN
      model with 5 nodes in input layer, 6 nodes in hidden layer, and 2 nodes in output
      layer would be obtained, and the transfer function of sigmoid was used in each
      layer. Then, this model was used to predict the samples in the validation set.
      The result indicated that a 100% recognition ration was achieved with the
      threshold predictive error +/- 0.1, the bias between predictive value and
      standard value was lower than 5%. It could be concluded that PCA combined with BP
      ANN was an available method for varieties recognition and pH mensuration of white
      vinegar based on Vis/NIR transmittance spectroscopy.

PMID- 18619306
TI  - [Application of wavelet packet entropy and Fisher classifier to the
      identification of medicinal rhubarbs with near-infrared spectrum].
AB  - The diffused-reflectance near-infrared (NIR) spectrum of medicinal rhubarbs was
      collected by Fourier transform spectroscopy instrument Principal components (PC)
      and wavelet packet entropy (WPE) were then calculated from the spectrum. Based on
      these two kinds of features, the models of identification of medicinal rhubarbs
      were developed using Fisher classifier. The results show that the error rates of
      cross-validation and prediction using WPE are all lower than those using PC. The
      model was built by WPE feature extraction method combined with Fisher classifier,
      the error rate of cross-validation is 6.52%, while that for prediction is 2.04%.
      The research result provides a method for identifying medicinal rhubarbs quickly.

PMID- 18619307
TI  - [The application of FTIR spectroscopy to the analysis of cigarette smoke].
AB  - In the present paper, Fourier transform infrared aerosol flow tube (FTIR/AFT) and
      Fourier transform infrared attenuated total reflection (FTIR/ATR) were used as
      credible technologies to study the cigarette mainstream smoke and cigarette
      aerosol. In the experiment a convenient and effective setup was used to detect
      the sample. Before the cigarette was fired, the filter tip should be cut. Then
      the cigarette was connected with the sample chamber by a gluey tube. The
      mainstream cigarette smoke was imported by a vacuum pump. The technology of
      FTIR/AFT could get the information of the whole cigarette smoke including the
      chief gas phase and fine solid particles. A main peak at 1 230 cm(-1),
      contributed by the C-O stretching band, indicated the existence of
      hydroxybenzene. A acuate peak at 1 735 cm(-1) was contributed by the C=O
      stretching band of carboxyl acide. In addition, the strong peak of CO and CO2 gas
      can be resolved. Two relative strong peaks at 2 118 and 2 170 cm(-1),
      respectively were contributed by CO gas. As to the gas CO2, two strong peaks were
      observed at 2 343 and 2 362 cm(-1), respectively. While by taking the advantage
      of FTIR/ATR, we could obtain the information of cigarette aerosols deposit on the
      ZnSe substrate. The spectra of aerosol was correspondingly simple. The peak of CO
      disappeared and the peak intensity of CO2 decreased greatly. Therefore, using the
      AFT and ATR techniques could help to understand the formation and the composition
      of the production of the burning cigarette more clearly. Especially, by analyzing
      the change of some characteristic bands with time, the processes of the chemical
      reaction, volatility of some components and theform conglomeration of cigarette
      combustion were investigated. This has offered a new viewpoint in cigarette study
      that is different from conventional ideas, and is simple and rapid without
      pretreatment.

PMID- 18619308
TI  - [Application of wavelet multi-scale orthogonal signal correction in milk
      components measurement using near-infrared spectroscopy].
AB  - Spectral interferences can have a significant impact on the spectral variation
      and as a consequence can adversely affect the results of calibration model in
      spectra analysis. Wavelet transform (WT) and orthogonal signal correction (OSC)
      were both the popular preprocessing algorithms. It was known that the former can
      effectively eliminate the background and noise and the latter can effectively
      filter out the interference information irrelevant to analyte concentration
      during the preprocessing of spectra. According to the different characteristics
      of analyte information and interference information in near-infrared (NIR)
      spectra, a new hybrid algorithm (WMOSC) that was the combination of discrete
      wavelet transform (DWT) and OSC was proposed to eliminate the spectral
      interferences including background, noise and systemic spectral variation
      irrelevant to the concentration. First, DWT was used to split the spectral signal
      into different frequency components, which keep the same data points as the
      original spectra data, to remove noise and background information by threshold
      method. Then OSC was applied to each frequency components to remove the
      information uncorrelated to the concentration independently. Finally, the spectra
      preprocessed by WMOSC were achieved through the summation of all frequency
      components. WMOSC was successfully applied to preprocess the NIR spectra data of
      milk. After elimination of the interference in the NIR spectra data by WMOSC, the
      partial least squares (PLS) regression was used to develop the calibration models
      for estimating the contents of main constituents in milk.The prediction ability
      and robustness of models obtained in subsequent PLS calibration using WMOSC were
      superior to those obtained using either DWT or OSC alone. The root mean square
      errors of prediction (RMSEP) of the models for fat, protein and lactose were
      0.101 6%, 0.087 1% and 0.110 7%, respectively. The experimental results show that
      WMOSC is an effective method for eliminating the interferences information in NIR
      spectra.

PMID- 18619309
TI  - [A simple and convenient standardization algorithm of NIR spectra].
AB  - Due to the limitation of current algorithms for NIR spectral analysis model
      transfer, a simple and convenient algorithm to standardize the spectra was
      proposed, and a new performance index called spectra standard error (SSE) was
      also constructed to evaluate the validity of model transfer algorithms. SSE
      expresses the ratio of J2 to J1, where J2 describes the distances between the
      spectra of the same sample using different instruments, and J2 describes the
      average distance between the spectra of different samples using the original
      instrument for their central spectrum. In the present paper we first used
      Savitzky-Golay smoothing to realize baseline correction for different spectra,
      and then applied standard normal variate method to standardize spectra and
      polynomial filtering to avoid noise. Besides, we optimized the wavelength range
      and the window width in Savitzky-Golay smoothing in order to minimize the SSE.
      After these steps, the standardized spectra can be applied to spectral analysis
      modeling. By the new algorithm, neither collecting a great number of samples nor
      need measuring all spectra of training samples using different instruments are
      needed. For a set of gasoline samples, SSE can be reduced from 1.418 to 0.167 via
      the new standardization algorithm and satisfactory results were obtained.

PMID- 18619310
TI  - [Inversion results of the atmospheric environment detecting airborne lidar in
      Qingdao, Bohai and Yellow Sea area].
AB  - Without the hypothesis of atmospheric parameters and auxiliary equipment, it is
      proven the slope method is capable of deriving extinction coefficients profiles
      and atmosphere optical depth through the analysis of the atmospheric environment
      detecting airborne lidar (AEDAL) data collected during November 7 to 11, 2005.
      The spatial and temporal variations of the planet boundary layer (PBL), aerosol
      optical depth (AOD) of the PBL and aerosol distribution along flight lines are
      exhibited from the AEDAL inversion results. Firstly, the sinking of aerosol was
      found in Yellow Sea area, moreover, the PBL altitude also dropped while the multi
      layer aerosol presented after a cold front passage; secondly, the AOD of the PBL
      is the highest over Qingdao city, the lowest over foothill area and in between
      them over sea area, Meanwhile, it is relatively stable over sea area but slightly
      increases nearby upslope. The AOD values of the PBL were determined to be 0.15
      0.35 in clear day and 0.3-0.45 in foggy day over the area from Qingdao to Bohai,
      but they are higher and reach around 0.55 in Yellow Sea area. It is evidenced
      that the aerosol in the PBL mainly comes from city and also is contributed by
      salt sea over Qingdao area, and ridge and surface wind play an important role in
      the aerosol transport while the monsoon affects the aerosol distribution.

PMID- 18619311
TI  - [Preliminary exploring of hyperspectral remote sensing experiment for nitrogen
      and phosphorus in water].
AB  - The content of nitrogen and phosphorus in the waters is an important index to
      measure water quality, and the technique of remote sensing plays a large role in
      monitoring the change in environment. The reflectance spectra of nitrogen and
      phosphorus with different concentrations were measured to discover their special
      features under pure water condition in the laboratory by hyperspectral remote
      sensing technique. The result shows that nitrogen has reflectance peaks at 404
      and 477 nm, and phosphorus at 350 nm, and these reflectance peaks have a good
      correlation with their concentrations, then a quantitative retrieval model was
      deduced for nitrogen and phosphorus based on that. These results will lay an
      important basis for further monitoring nitrogen and phosphorus by remote sensing
      technique in the big inland lakes, reservoirs and rivers.

PMID- 18619313
TI  - [Study on the vibrational spectra characterization of synthetic jadeite jade made
      by General electric Company].
AB  - The object of the present study is the synthetic jadeite jade produced by
      American General Electric Corporation. Fourier transform infrared spectroscopy
      (FTIR) and Laser Raman spectroscopy were used to test its spectral properties in
      order to examine the feature of this kind of synthetic jadeite jade by
      vibrational spectroscopy and to figure out the mark for discriminate synthetic
      jadeite jade from natural jadeite jade. The study shows that GE synthetic jadeite
      jade is identical with natural jadeite jade in the main on fingerprint region in
      FTIR; There are clearly differences in the 2 000 -4 000 cm(-1) functional region
      in FTIR: a group of frequencies at 3 375, 3 471 and 3 614 cm(-1) indicate
      vibration absorption of O-H. GE synthetic jadeite jade has proven consistent with
      natural jadeite jade in the laser Raman spectra by a group of sharp scattering
      peaks at 376, 700, 989 and 1 039 cm(-1). In addition these scattering peaks show
      an intact crystal shape. The FTIR peaks and Raman spectral peaks shift to higher
      frequencies showing GE synthetic jadeite jade lacking isomorphism of heavy
      positive ions.

PMID- 18619312
TI  - [Study on the stability of pesticide WDG suspension by TURBISCAN LAB].
AB  - TURBISCAN LAB has been applied to analyze the stability of pesticide WDG (water
      dispersible granule)suspension. With the application of poly (styrene sulfonic
      acid -co- acrylic acid) sodium salt dispersant made by ourselves in a formula of
      75 wt% tribenuron WDG, and by measuring the change in the intensity of
      transmission and backscattering light in pesticide WDG suspension with time, the
      dynamic sedimentation process of pesticide WDG suspension with time can be
      described in-situ, reflecting the stability of pesticide suspension system. It
      was found that when the contents of polymer dispersant were about 6 wt% in the
      WDG, and the average molecular weight was about 15 000, the stability of WDG
      suspension system was relativelygood. Through studying the thickness of
      sedimentation, the settling rate of particles, the particle size, and the
      increasing rate of particle diameter in the suspension system in various kinds
      and contents of polymer dispersant, it has been made more convenient and
      efficient to sift the accessory ingredient in the formula of dosage form as well
      as to optimize the formula of pesticide WDG.

PMID- 18619314
TI  - [Spectroscopic studies on interaction of bovine hemoglobin and realgar
      nanoparticles].
AB  - In the present paper, the interaction of bovine hemoglobin (BHb) and realgar
      nanoparticles has been investigated by ultraviolet-visible (UV-Vis) and
      fluorescence spectroscopy. The Soret band of oxygen-BHb at 406 nm shifted to 413
      nm, and its absorption intensity decreased gradually after adding realgar
      nanoparticles. The Soret band decreases gradually with the increasing the amount
      of realgar NPs, suggesting the detachment of some heme chromophores from their
      matrixes in BHb. The red-shift of characteristic peak leads to be conjecture that
      the arsenic of realgar combined with the oxygen of BHb. The oxygen-BHb was
      deoxidated by realgar nanoparticles, and the surface binding induces conformation
      change of BHb from the high-affinity R state to the low-affinity T state. The
      fluorescence intensity of BHb is quenched by realgar nanoparticles when its
      concentration gradually increased. The analysis of Stern-Volmer equation revealed
      that the mechanism was a static quenching procedure. The order of the magnitude
      of binding constant k was 10(9), obtained from the calculation of UV-Vis and
      fluorescence spectra.

PMID- 18619315
TI  - [Thermodynamics studies on the binding of rutin and serum albumin].
AB  - To study the binding of rutin and serum albumin (SA) in physiological condition
      and the quenching mechanism of the fluorescence of SA by rutin, the fluorescence
      method was used. The results shows that the emission spectra of BSA (HSA) in the
      presence and absence of rutin are different. The emission spectra of BSA (HSA) in
      the presence of rutin can be quenched. The quenching mechanism of rutin to SA was
      static quenching with non-radiation energy transfer with single molecule. The
      binding constants K(A), the number of binding sites n and the thermodynamic
      parameters of the reaction of rutin with SA were determined at different
      temperatures. At 295 and 310 K, for BSA, K(A)(L * moL(-1)) = 4.215 x 10(4) and
      6.996 x 10(3) and n = 0.75 and 0.64, respectively; for HSA, K(A)(L * moL (-1)) =
      2.660 x 10(4) and 4.110 x 10(3) and n = 0.70 and 0.60, respectively. The binding
      constants K(A) decreased with the increase in temperature, which means that rutin
      and SA have a quite strong ability to form a new complex-system. The main binding
      force was discussed by thermodynamic equation, and the result is that deltaH < 0
      and deltaS < 0 for the reaction of rutin with SA. So the binding forces was
      mainly H-bond and Van der Waals. The effect of the drug on the conformation of
      serum albumin was also studied by using synchronous fluorescence spectroscopy.
      Rutin could be deposited and transported by serum protein in vivo. Rutin had
      nearly no effect on the serum protein conformation.

PMID- 18619316
TI  - [Quantitative analysis of electronic absorption spectroscopy by piecewise
      orthogonal signal correction and partial least square].
AB  - Electronic absorption spectroscopy (EAS), as an indirect analytical technique,
      has been used to carry out quantitative analysis of unknown samples by
      establishing a model with calibration samples. Partial least squares (PLS), as a
      powerful technique for process modeling and multivariate statistical process
      control, has been widely used to establish this model. On account of the noise
      signal in the spectra, the signal preprocessing was often a necessary step in
      building reliable and robust multivariate calibrations. The main goal of
      preprocessing was to remove variation in the data that was irrelevant to
      modeling. Orthogonal signal correction (OSC) and related methods emerged as
      filtering techniques for various spectra in modern chemometrics literature.
      However, it was confirmed in recent work that preprocessing with OSC did not lead
      to any significant improvements in calibration models subsequently developed by
      means of PLS regression, except for merely reducing the number of latent
      variables in the PLS model by the number of OSC components removed. Now in our
      study, taking into account the local effect sensitivity and numerous predictor
      variables with serious multicollinearity of the spectra data, a novel PLS
      algorithm that embedded the OSC into the regression framework of the PLS, termed
      as POSC-PLS method, was implemented. It firstly applied the OSC technique to a
      set of selected spectra at an optimized size of moving window, namely piecewise
      OSC (POSC), to pretreat the spectra matrix and eliminate the local variance, thus
      the spectra matrix pretreated was taken as the new independent variables matrix,
      then the PLS algorithm was applied to build the calibration model. Finally,
      application of the proposed POSC-PLS approach to the EAS quantitative analysis of
      the polyaromatic hydrocarbons (PAHs)was presented for comparison with the MLR
      (multiple linear regression), PLS and OSC-PLS methods. The result indicates that
      the POSC-PLS approach by performing POSC prior to calibration not only can
      improve the model accuracy, but also decreases the PLS factors compared to the
      models obtained by the above rest methods and so its resulting model becomes more
      concise. The removal of orthogonal components from the response matrix is greatly
      facilitated simply by considering localized spectral features. So, preprocessing
      with POSC was shown to benefit the multivariate PLS model because it performed a
      localized regression modeling procedure that differs from that of PLS. At the
      same time, the POSC is a potential chemometric technique in the pretreatment of
      various spectra.

PMID- 18619317
TI  - [The study of aluminium diffuser calibration in the UV].
AB  - A bi-directional reflectance distribution function (BRDF) measurement setup in
      the ultraviolet spectral range was established. The BRDF of the aluminium
      diffusers at a given orientation was measured. The relative accuracy of the BRDF
      measurement is better than 2.5%. The hemispheric reflectance of the aluminium
      diffusers was measured in the wavelength range from 250 to 650 nm. It increases
      with the wavelength, and changes about 6% from 300 to 360 nm. It decreases with
      the time. Since the diffuser was made (about one year ago), from 250 to 300 nm,
      the peak decrease in the hemispheric reflectance can reach 2.6%, and the average
      decrease is 1.5%. From 300 to 360 nm, it has an average decrease of 0.9%
      decrease, and 0.8% when wavelength is longer than 360 nm.

PMID- 18619318
TI  - [Synchronous measurement of concentrations of nitric oxide and nitric dioxide in
      flue gas by ultraviolet absorption analysis].
AB  - Ultraviolet absorption optical depths of NO and NO2 gas mixture with different
      concentrations were measured, using a high resolution grating monochromator. By
      correlating fast-varying discrete absorption and slow-varying continuous
      absorption with NO and NO2 contributions respectively, the mole concentrations of
      NO and NO2 were derived synchronously. The study results indicated that, when the
      total pressure of gas mixture approached to one atmospheric pressure, a strong
      tendency that two moles of NO2 were combined into one mole of N2O4 was found. The
      maximum conversion rate from NO2 to N2O4 was roughly 22.5%, resulting in the fact
      that the effective absorption cross-section of NO2-N2O4 mixture mainly depended
      on that of N2O4, which exhibited continuous characteristics in its absorption
      spectrum. The discrete absorption cross-section spectrum was broadened with the
      increase in the partial pressure of NO. It was shown that the integral of
      absorption cross-sections within a discrete absorption band had better linear
      correlation with NO concentration than the discrete absorption cross-section peak
      The measurement and derivation results indicated that, when the partial pressure
      of NO2 varied within 17-100 Pa, the average relative error for the derived NO2
      concentration was 11.7%. When the partial pressure of NO varied within 63.8
      181.62 Pa, the maximum and average relative error for the derivation of NO
      concentration was 16.9% and 9.6% respectively by using the spectrum integral
      method, while the corresponding data rose to 38.2% and 14.4% by using the
      spectral peak method. The technique can be applied to synchronous monitoring of
      NO and NO2 concentration with relatively simple measurement hardware.

PMID- 18619319
TI  - [Observation and analysis of solar ultraviolet irradiance spectrum in Chengdu
      area].
AB  - The solar ultraviolet irradiance spectrum in Chengdu area from March to July in
      2006 was observed with an ultraviolet CCD optical multi-channel analyzer.
      According to the observation results, some analysis of the basic characteristics
      was made. The analysis of the solar ultraviolet irradiance spectrum showed that
      the solar ultraviolet irradiance is weak in the morning and in the evening but
      strong at noon, reaches the strongest point in June, and reversely correlates
      with the change in SZA (solar zenith angle); the ratio of irradiance flux of UVB
      to UVA is less than 0.04, and usually, the ratio in the afternoon is bigger than
      that in the morning in sunny days; Fogs can cause the ratio to increase, the
      reason is that fogs show stronger influence on attenuation of UVA than UVB;
      Clouds absorbed the solar ultraviolet irradiance greatly.

PMID- 18619320
TI  - [Study on structure and spectra of 1,4-bis[(p-methoxyphenoxy) carbonyl]].
AB  - Theoretical studies on 1,4-bis [(p-methoxyphenoxy) carbonyl] and ramification
      were carried out using the density functional theory at B3LYP/6-31+G* level to
      obtain optimized equilibrium structure, vibrational spectra and electronic
      spectra. The calculation results indicate that the carbon and oxygen (in the
      ester group) come into being different large pi bonds with the benzene circles
      because of place blocking and conjugate effect. On this basis, the first excited
      state electronic transition energy was calculated by time-dependent density
      function theory. The calculated results show that the largest absorption spectra
      of the title compounds were obtained from the pi --> pi* electron transition from
      the highest occupied molecular orbital to the lowest unoccupied molecular
      orbital. And lambda(max) was obtained in 370-384 nm, belonging to the UV
      absorption area. The computed results show that the lateral substitutent of 1,4
      bis [(p-methoxyphenoxy) carbonyl] has little effects on molecular structure.
      Because of place blocking, the dihedral angle between benzene (1) and benzene (2)
      augments 3 degrees-4 degrees. The introduction of the lateral substitutents has
      effects on vibrational spectra. The results showed that with the introduction of
      hydroxy the difference between E(HOMO) and E(LUMO) of the compound becomes small.
      While lambda(max) becomes large. Meanwhile, the difference between E(HOMO) and
      E(LUMO) reduces by 0.120 9 eV with the introduction of fluorin. This causes the
      biggest absorption wavelength to red shift 14 nm.

PMID- 18619321
TI  - [Synthesis, characterization, spectroscopy and theoretical calculation of two
      novel carbazole derivatives].
AB  - Two novel carbazole derivatives, 3-acetyl-9-n-hexylcarbazole (AHCZ) and 3, 6-
      diacetyl-9-n-hexylcarbazole (DHCZ) were synthesized through Friedel-Crafts
      reaction. The compounds were characterized by IR spectra, 1H NMR, MS and
      elemental analysis. UV-visible spectra of AHCZ and DHCZ were measured and
      compared with those of their precursors, 9-hexylcarbazole(HCZ) and carbazole(CZ).
      DHCZ and AHCZ exhibited strong absorption band, revealing the extent of pi
      conjugation in the system. TD-DFT method was performed to analyze the electronic
      absorption spectra of AHCZ and DHCZ, and the calculated excitation energies and
      oscillator strengths were compared with the experimental results.

PMID- 18619323
TI  - [Immunoresonance scattering spectral assay of complement factor 4(C4)].
AB  - Based on resonance scattering (RS) effect of immune complex particles, a new
      resonance scattering method for the determination of C4 in the human blood serum
      was developed. It was based on the fact that goat anti-human C4 was combined with
      complement factor 4 (C4) in the pH 7.3 Na2 HPO4-KH2PO4 buffer solution. It is
      known that antibody has C-terminal and N-terminal, and the N-terminal is the
      binding site of antigen and it could combine with antigen. Because the stereo
      structure anastomoses and the charge is opposite between goat ant-human C4 and
      C4, they could attract and combine with each other. The attraction and
      combination have high idiosyncrasy and they are done by Van der Waals force,
      hydrophobic force, Coulomb attracting force and hydrogen bond binding force, and
      form immune complex particles that exhibit three resonance scattering peaks at
      350, 390 and 440 nm, respectively, in the presence of PEG-6000. The laser
      scattering results indicate that the average diameter of the immune complex
      particles is about 3 440.0 nm. The influence of pH, goat anti-human C4 and PEG
      6000 concentration, incubation temperature and incubation time, foreign substance
      such as arginine, -phenyl alanine, L-glutamic acid, L-cystine, L-threonine, L
      tryptophan, L-histidine, L-leucine, glucose, EDTA, human serum albumin (HSA),
      bovine serum albumin (BSA), L-proline, L-lysine on the determination of C4 was
      considered in details. Under the conditions chosen, C4 concentration in the range
      from 0.18 to 2.60 microg x mL(-1) is proportional to the resonance scattering
      intensity at 350 and 390 nm. Its regression equation is deltaI350 nm = 28.23c +
      9.17 and deltaI390 nm = 31.36c + 11.08, the correlation coefficient is 0.993 9
      and 0.992 3, and the detection limit is 0.084 microg x mL(-1) and 0.11 microg x
      mL(-1), respectively. The method has been applied to the determination of C4 in
      the human blood serum, and the results are in agreement with that of the
      immunoturbidity, with relative standard deviation of 1.88%-4.36%, and with some
      advantages including simplicity, rapidity, high sensitivity and selectivity.

PMID- 18619322
TI  - [Study on the interaction between ICT fluorescence probe and bovine serum
      albumins].
AB  - The present article studied the interaction between intramolecular charge
      transfer fluorescence probe-1-keto-2-(p-dimethylaminobenzal)
      tetrohydronaphthalene (KDTN) and bovine serum albumins (BSA). With the
      concentration of KDTN increasing, the fluorescence of BSA rapidly quenched and
      the fluorescence peak gradually blue-shifted. The result indicated that they were
      bound mainly by hydrophobic interaction. The binding sites is 0.94 (3 degrees C)
      and the equilibrium constant K is 3.27 x 10(4) L x mol(-1). Temperature increment
      is advantageous to the combination. It is a single static quenching process that
      the fluorescence of BSA quenches, which is induced by the combination of KDTN and
      BSA. Further study showed that different substances had different effects on the
      combination of KDTN and BSA.

PMID- 18619324
TI  - [Feature abstraction and spectral reconstruction of three-dimensional
      fluorescence spectra of oil in water].
AB  - In the present paper, spectral reconstruction of three-dimensional fluorescence
      spectra of oil was studied based on singular value division (SVD) of fluorescence
      excitation-emission matrix (EEM). Depending on oil components, three-dimensional
      (3-D) fluorescence spectra of oils can be seen as their "fingerprints". Feature
      abstraction and selection of 3-D fluorescence spectra is important to oil
      identification. Statistic parameters such as the average, standard error,
      centroid, kurtosis, geometrical distribution as well as main-shaft slope
      selected, forming "apparent statistic feature" vector of 3-D fluorescence spectra
      of oils, are limited due to their roughness. And the apparent statistic feature
      vector can not support spectral reconstruction reversely. In this paper, with
      singular-value features abstracted from EEMs composing the feature chain,
      reversal spectral reconstruction can be realized, and its information loss can be
      estimated. In other words, a pan-gene series of 3-D fluorescence spectra consists
      of singular values and their corresponding accompanying vectors. By SVD operation
      on EEMs of dozens of oil samples in water, their singular values accompanied with
      corresponding vectors were calculated showing obviously gathering energy
      distribution. With singular values being properly cut, principal feature
      parameters were selected and combined with their accompanying vectors composing
      the pan-gene series (or singular-value pan-gene chain) and spectral
      reconstruction was reversely completed. A couple of spectra (original and
      reconstructed) of diesel as the typical oil in water were presented for
      comparison. It can be seen that there is no obvious difference between the
      reconstructed and original spectra. Certainly, information loss exists but in an
      scheduled extent. It is shown that the singular-value features of fluorescence
      excitation-emission matrix (EEM) represent spectral gathering energy, and the
      length-limited pan-gene chain has the ability to reconstruct three-dimensional
      fluorescence spectra. Practically, for common kinds of mineral oils such as
      crude, diesel, kerosene and lubricant, the preceding three principal parameters
      are enough to complete spectral reconstruction and oil identification, with every
      singular value being followed by its right accompanying vector respectively. This
      is meaningful for recognition of contaminating oil in water, and important to
      construct oil fluorescence database.

PMID- 18619325
TI  - [Investigation and application of fluorescence reaction of cerium-L-tryptophan in
      Triton X-100 microemulsion].
AB  - In the present article, the sensitizing effect of Triton X-100 microemulsion
      media (Triton X-100-M) on the determination of L-tryptophan by fluorescence
      spectrophotometry was studied, which was based on a strong fluorescence substance
      produced when L-tryptophan was oxidized by Ce4+ in acid medium. Compared with
      Triton X-100 micelle (Triton X-100-m), it was found that in the medium of Triton
      X-100-M the intensity of fluorescence was enhanced by 225 times. Various factors
      that influence fluorescence determination and interfering ions were examined. The
      mechanism of sensitizing effect of Triton X-100 microemulsion was also discussed.
      Under the optimum conditions, the liner range and detection limit are 0.1-1.0 g x
      mL(-1) and 0.09 microg x mL(-1) (correlation coefficient r = 0.998 4),
      respectively. The linear equation was F = 342.37+30.45c. The proposed method has
      been successfully applied to determine food samples.

PMID- 18619326
TI  - [Study on the interaction between cinnamic acid and human serum albumin by
      fluorescence quenching method].
AB  - The albumin is the richest protein in blood circulatory system, which can combine
      with many drugs and play an important role in transporing protein. In the present
      work, the non-covalent interaction between human serum albumin and cinnamic acid
      was studied by using fluorescence quenching method. The results showed that
      cinnamic acid had a powerful ability to quench the fluorescence of human serum
      albumin at excitation and emission wavelengths of lambda(ex) = 286 nm and
      lambda(ex) = 340 nm, respectively, in the reaction solution of pH 7.4. The
      binding constants(K) at 37 and 47 degrees C were found to be 1.276 7 x 10(3) and
      3.404 1 x 10(3) L x mol(-1), with the number of binding site(n) of 0.758 6 and
      0.835 6, respectively, suggesting that the reaction temperature is advantageous
      for the binding reaction in a way. The changes in the thermodynamic parameters of
      binding interaction at 37 and 47 degrees C indicated that the main binding force
      between cinnamic acid and human serum albumin was hydrophobic force. These
      provide important information for studying the pharmacological effects of
      cinnamic acid and the influence of cinnamic acid on the configuration change of
      HSA.

PMID- 18619327
TI  - [Studies on the interaction between alpinetin and human serum albumin by
      fluorescence spectroscopy].
AB  - The interaction between alpinetin and human serum albumin (HSA) was studied by
      fluorescence and UV/Vis absorption spectroscopy. The results revealed that
      alpinetin caused the fluorescence quenching of HSA through a dynamic quenching
      procedure. The quenching constant was obtained at various temperatures. The
      binding locality was found to be an area 4.05 nm away from tryptophan residue in
      HSA based on Forster's non-radiation energy transfer mechanism. The binding power
      between alpinetin and HSA is mainly the hydrophobic interaction according to the
      thermodynamic parameters. The effect of alpinetin on the conformation of HSA was
      analyzed by three-dimensional fluorescence spectra, contour spectra and
      synchronous spectra.

PMID- 18619329
TI  - [Determination of hydrogen peroxide in rainwater by fluorometry].
AB  - The present paper introduces a new method using spectrofluorimetric analysis to
      determine the concentration of hydrogen peroxide in rainwater. In this method, an
      oxidation reaction is conducted between o-phenylenediamine (OPDA) and hydrogen
      peroxide in the buffer medium of NaAc-HAc at pH 4. 48 to form a new product 2,3
      diaminophenazine (DAPN). Then the fluorescence intensity of DAPN is measured and
      426 and 554 nm are chosen as the excitation and emission wavelengths. Therefore,
      with the foreknown concentration of input hydrogen peroxide, a series of
      fluorescence intensities of DAPN are acquired according to a series of different
      concentration of hydrogen peroxide as input, greatly improving the selectivity
      and sensibility of the system. A relationship between the input concentration of
      hydrogen peroxide and the fluorescence intensity of DAPN is then obtained using a
      linear regression. Results show that fluorescence intensity of DAPN is in
      proportion to the increase in the concentration of hydrogen peroxide in the range
      of 9.0 x 10(-7) -3.56 x 10(-5) mol x L(-1) almost linearly. The linear equation
      is F = 1.15c (micromol x L(-1))+398.6 (r = 0.999 1) and the detection limit is
      2.7 x10(-7) mol x L(-1) (n = 11). The relative standard deviation of 11 parallel
      measurements with the concentration of H2O2 at 7.5 x 10(-6) and 3.0 x 10(-5) mol
      x L(-1), is 2.2 and 1.0%, respectively. Results from DPD method was used to
      verify this method. The interference of foreign iron was studied. Compared to the
      traditional methods, this binary system has a simplified operation and high
      sensitivity. The proposed method has been successfully applied to determine the
      concentration of hydrogen peroxide in rainwater.

PMID- 18619330
TI  - [Preparation and catalytic activity for degradation of acidic fuchsine of TiO2
      photocatalyst].
AB  - In the paper, undoped and Pr2O3 doped TiO2 nanoparticles were prepared by a sol
      gel process using Ti(OC4H9)4 as raw material and characterized by means of XRD TG
      DTA, AFM, UV-Vis and FTIR. The photocatalytic activity of Pr2O3/TiO2 was
      evaluated by the photocatalytic degradation of acidic fuchsine. The factors
      affecting on photocatalytic activity of Pr2O3/TiO2, such as the content of doped
      Pr2O3, the calcined temperature and added amount of the catalyst etc. were
      discussed. It was shown that Pr doping hampers the transformation of TiO2 crystal
      phase from anatase to rutile, and with Pr2O3 doping the particle diameter of
      Pr2O3/TiO2 samples decreased, the specific surface area increased and the
      photocatalytic activity improved. When doping amount of Pr is 0.8%, added amount
      of the catalyst is 0.03 g and the calcination temperature is 500 degrees C, the
      degradation efficiency of acidic fuchsine reaches 97%. The photocatalytic
      degradation of acidic fuchsine by Pr2O3/TiO2 is a quasi-first order dynamic
      reaction.

PMID- 18619328
TI  - [Bovine serum albumin in the presence of zinc (II) by fluorescence method].
AB  - The interaction between norfloxacin and bovine serum albumin, and the influence
      of Zinc (II) on the system of norfloxacin and bovine serum albumin was studied
      under physiological condition by fluorescence method. It was shown that
      norfloxacin has a powerful ability to quench the BSA fluorescence via a
      nonradiative energy transfer mechanism. The fluorescence quenching data were
      analyzed according to Stern-Volmer equation and double-reciprocal equation, and
      the binding constant (K) and the binding sites (n) were obtained. In the system
      of binary complex of NFLX and BSA, K = 6.80 x 10(5) and n = 1.21. There is a
      strong combination between NFLX and BSA, which offers the condition for the serum
      protein to be deposited and transported in vivo. Besides, the combination between
      NFLX and BSA becomes stronger in the presence of Zinc (II). According to Stern
      Volmer equation and double-reciprocal equation, the concentration of Znic (II) is
      denser, and the binding constant (K) and the binding sites (n) are bigger. By
      studying the binding interaction between Zinc (II), norfloxacin and BSA, the
      mechanism of the interaction among norfloxacin, Zinc (II) and protein in
      organism, is furtherly discussed.

PMID- 18619331
TI  - [Study on the spectra of Au/CeO2 catalysts modified by La2O3 additive].
AB  - For Au-ceria catalysts prepared by deposition-precipitation method, the catalytic
      performance of water gas shift reaction was studied with different La loadings.
      In the complete doping range, ceria retains with its cubic fluorite structures.
      XRD, HRTEM and UV-Vis-DRS, studies showed that La doping can improve the activity
      of Au-ceria catalyst by stabilizing ceria and modifying its morphology. In
      addition, the test of catalyst stability evaluation also proved, that a better
      stability performance of Au-ceria catalyst can be realized by appropriate La
      doping. The Au/CL5.0 sample with 5 at % La doping showed the best performance in
      WGS reaction.

PMID- 18619332
TI  - [Determination of minor elements in stainless steel by laser-induced plasma
      spectroscopy (LIPS)].
AB  - Laser-induced plasma spectroscopy (LIPS) is characterized by its non-contact and
      real-time analysis. Its application to the determination of steel composition can
      meet the need of high-speed, continuous and automatic production in large steel
      companies. In the present article the minor elements concentrations of aluminum,
      manganese, cobalt, molybdenum, and titanium in a series of stainless steel
      1Cr18Ni9Ti samples were determinate by laser-induced plasma spectroscopy, based
      on a Nd : YAG Q-switched solid laser with wavelength 1 064 nm as an exciting
      source and ICCD as detector. In the experiment the working delay time and gate
      time of ICCD were set suitably to get high signal-to-noise ratio emission
      spectral lines, and the internal standardization method related to matrix effect
      was used to deal with spectral data. Experiment results show that the
      concentration ratios of all the measured elements versus the reference element
      ferrum have a good linear relationship with the intensity ratios of them, the
      detection limits of the five tested elements are within 150 microg x g(-1).

PMID- 18619333
TI  - [Effects of soil use along Yellow River basin on the pollution of soil by heavy
      metals].
AB  - Because of the decrease in pasture and woodland proportion, soil loss is severe
      along the Yellow River basin. The Yellow River delta has been one of the deltas
      that form land most quickly. Research on the pollution of new land is important
      for its use and appraising the environment and food pollution along Yellow River
      basin. The contents of heavy metals (Mn, Cu, Zn, As, Cd, Pb, Hg and Cr) in new
      soils (2006) and old soils (1996) from Yellow River delta, were analyzed by the
      method of ICP-MS/ICP-AES, in order to determine the level of pollution along
      Yellow River basin. The results showed that the heavy metals pollution along
      Yellow River basin is increasingly severe, especially the concentrations of Mn,
      Cu, Zn, Cr and Cd in soil forming in 2006 are significantly higher than those in
      1996, which should be noticed by our government.

PMID- 18619334
TI  - [Application of ICP-MS to detection of mineral elements and heavy metals in
      transgenic cotton fibre].
AB  - With the rapid development of transgenic cotton, people begin to focus on its
      physiology and ecology. The present paper studied the contents of heavy metals
      and microelements in transgenic cotton fibre by ICP-MS/ICP-AES. The results
      showed that the contents of most microelements (B, Mg, Mn, Fe, Co, Ni, Cu, Zn, Se
      and Mo) detected in transgenic cotton fibre were lower those in regular cotton
      fibre, especially the contents of Zn which was several times lower. But the
      concentrations of Na, Si, P, K and Ca in transgenic cotton fibre were higher than
      those of regular cotton fibre, especially for Si. The concentrations of the heavy
      metals detected (Al, Pb, Cr, Cd, Sb, Tl and As) in transgenic cotton fibre were
      all lower than those in regular cotton fibre. All the data showed that the
      accumulation patterns of heavy metals and microelements in transgenic cotton
      fibre were clanged by the insertion of foreign genes.

PMID- 18619335
TI  - [Determination of metal elements in Mongolian medicine Chagederi by ICP-AES with
      microwave digestion].
AB  - In the study of the Mongolian medicine we found that the Mongolian medicine
      contains a great amount of trace elements and nutrition composition of amino
      acids etc, in which trace elements that human body needed are fairly rich but the
      heavy metals are very little. A method for the determination of Ca, Mg, Al, Fe,
      Mn, Sr, Cu, Zn and Pb in Mongolian medicine Chagederi (1# and 2#) by ICP-AES with
      microwave digestion was studied. The recoveries of standard addition are in the
      range of 97.5%-105.5%. The relative standard deviation is < or = 2.88, and the
      detection limit is in the range of < or = 0.009 microg x L(-1). The results show
      that 1# and 2# have some differences and the medicine property and drug effect
      has some relation with trace elements.

PMID- 18619336
TI  - [Determination of mercury in Boletus impolitus by flow injection-atomic
      absorption spectrometry].
AB  - Various test conditions and effect factors for the determination of mercury by
      flow injection-atomic absorption spectrometry were discussed, and a method for
      the determination of mercury in Boletus impolitus has been developed. The linear
      range for mercury is 0-60 microg x L(-1). The relative standard deviation is less
      than 3.0%, and the recovery is 96%-107%. This method is simple, rapid and has
      been applied to the determination of mercury in Boletus impolitus samples with
      satisfactory results.

PMID- 18619337
TI  - [Spectral analysis of ceramic-painting pigments from Taosi site].
AB  - Based on the analysis of Raman, IR spectroscopy and XRD methods, the structure of
      the different pigments and bond in red pigment in the ceramic from Taosi site in
      Xiangfeng county, Shanxi province was analyzed. It is very prominent that both
      red and white pigments have been well preserved. The red pigment was identified
      as HgS, while white pigment is CaCO3, and the bond in red pigment is CaCO3, which
      was made from white lime, and the reasons for its formation is because of carbon
      dioxide in air, which was absorbed by white lime over long history. Moreover, it
      was indicated that the Raman and IR spectra are more effective for identifying
      the ancient pigments in very few quantities than XRD. Furthermore, the fact that
      quartz was unfound in vermilion, suggested that the technique for synthetic
      vermilion might have been known in 4 000 years ago in Taosi site.

PMID- 18619338
TI  - [Studies on simultaneous quantitative determination of overlapping spectra using
      chemometric techniques].
AB  - Based on comparative study of eight chemometric denoising methods, a wavelet
      packet transform Elman recurrent neural network (WPERNN) method was developed to
      study simultaneous quantitative determination of overlapping spectra. The quality
      of noise removal and ability of regression were improved by combining wavelet
      packet transform with Elman recurrent neural network. Through optimization, the
      wavelet function, the wavelet packet decomposition levels as well as the
      structure and parameters of Elman recurrent neural network were selected. Two
      programs, PWPERNN and PERNN, were designed to perform WPERNN and ERNN
      calculation. Seven kinds of chemometric methods were applied in the present study
      for comparison. Experimental results showed that the WPERNN method was successful
      and better than the other 6 methods.

PMID- 18619339
TI  - [Optimally designing the probe of the near infrared oximeter to detect human
      tissue oxygen saturation non-invasively].
AB  - Human tissue oxygen saturation (rSO2) can be monitored non-invasively and in real
      time by near infrared spectroscopy (NIRS) based on spatially-resolved
      spectroscopy. To expand the clinical applications of the NIRS oximeter developed
      by our group based on the above principle, the accuracy of rSO2 must be ensured
      and enhanced as far as possible. In the present paper, the influences of the
      probe configuration, especially the distance between the detectors and the
      wavelength discreteness of the light source, on the accuracy of rSO2 were
      discussed. The results indicate that (1) to obtain rSOz accurately, two detectors
      need to be used, where the distance between them should be in the range of 5-20
      mm and they should be both at least 20 mm apart from the light source; (2) there
      can be significant error in rSO2 (> 10%) induced by the discreteness of the two
      emission wavelengths especially the shorter one of the light source, so the real
      emission wavelengths must be accurately measured and the corresponding extinction
      coefficients of deoxygenated and oxygenated hemoglobin (Hb and HbO2) must be used
      in order to avoid this error. The above conclusions can be the guidance to
      optimally design the probe, which has been achieved in our NIRS oximeter.

PMID- 18619340
TI  - [Study on geographical variation of morphologic and germination characteristic of
      different Glycyrrhiza uralensis provenance seeds].
AB  - OBJECTIVE: To study the geographical variation of morphologic and germination
      characteristic of different Glycyrrhiza uralensis provenance seeds, approach the
      geographical variation mode and ecology mechanism, and laid theoretical
      foundation for districting and allocating of G. uralensis seeds. METHOD: Field
      investigation and laboratory analysis were applied. Seed shape and kilosseed
      weight were sampled randomly, germination rate germination force by general
      methods. RESULT: The morphologic characteristic of G. uralensis seeds showed
      roughly longitude variation tendency that the seeds increased gradually from west
      to east. While the germination characteristic showed roughly altitude variation
      tendency that the seeds germination rate and germination force increased with the
      increase of the altitude, and the average germination rate was the same with the
      seeds morphologic characteristic. The results of analysis correlated with the
      climatic factors show that the morphologic characteristic of G. uralensis was
      positive correlated with annual rain-fall of the habitat, and the germination
      rate was quickened by drought, high temperature and strong sunshine. CONCLUSION:
      The morphologic and germination characteristic and of G. uralensis seeds present
      distinguished geographical variation, and the formation of the variation was
      related to the ecological environment in which the seed provenance adapted.

PMID- 18619341
TI  - [Effects of microbes on rooting and on several physiological and biochemical
      indexes of cuttings of Huperzia serrata].
AB  - OBJECTIVE: To study the effects of soil microbes of habitats, endophytic fungi
      and root surface fungi of Huperzia serrata on rooting rate of the cuttings and on
      several physiological and biochemical indexes. METHOD: The cuttings of H. serrata
      were planted on soil I of primary habitat, the soil II had been inoculated
      endophytic fungi and root surface fungi, the soil III had been auto-claved,
      rooting rate was examined, and soluble protein and soluble sugar contents,
      activities of PPO and POD, flavonoids and huperzine A contents were determined.
      RESULT: Compared with the H. serrata that were planted on soil III, soil I and
      soil II were found to increase the rooting rate by 10% and 16%, soil II increased
      the soluble protein contents of stem of H. serrata (P < 0.05), Soil I increased
      the soluble sugar contents of leaves and stem of H. serrata (P < 0.05), soil I
      and Soil II increased the flavonoids contents of H. serrata (P < 0.05).
      CONCLUSION: Soil microbes from primary habitat, endophytic fungi and root surface
      fungi promote rooting, they also increase plant metabolism level of H. serrata.

PMID- 18619342
TI  - [Growth and propagation of wild Pinellia ternata in cultivation].
AB  - OBJECTIVE: To study the growth and propagation of Pinella ternata in cultivation.
      METHOD: Forty six populations of P. ternata originated from Sichuan, Shanxi
      province and chongqing city were collected and cultivated in experimental field
      under the same cultivation condition. RESULT AND CONCLUSION: Reproduction tubers
      at the weight of 0.51-2.00 g (diameter 0.9 - 1.5 cm) had higher increments of
      tubers and general weight. The P. ternata populations originated from Peng-an
      county, Shehong county, Zhongjiang county, Lezhi county, Lu county grew faster,
      on the other hand, the populations originated from Lezhi county, Guangyuan
      county, Peng-an county, Jianyang county had stronger ability of propagation. The
      sprouting rate of above 0.30 g (diameter 0.7 cm) tubers was about 90%. There was
      no significant difference in the growth between tubers and bulbils that have the
      same weight. The two factors that affected the yield increment were weight range
      and population, and the former was the main one. Significantly positive
      correlations were found between weight of reproduction tuber and weight of
      harvested tubers, number of bulbils. However, significantly negative correlations
      were found between weight of reproduction tuber and weight increments of tubers,
      increments proportion of tubers and general weight, and a negative correlations
      was found between weight of reproduction tuber and general weight increments.
      Curve-estimated models were conjectured about the weight of reproduction tuber
      and growth or propagation parameters such as the diameter, the sprouting rate,
      increments of tubers and general weight, increments proportion of tubers and
      general weight and the number of bulbils. Some proposals to improve the
      cultivation of P. ternate were suggested.

PMID- 18619343
TI  - [Study of liquorice processing fructus].
AB  - OBJECTIVE: To establish the processing method of fructus evodiae and its standard
      for quality control, toxicity aspects and pharmacodynamics were carried out at
      the same time. METHOD: In the studies of processing techniques, the optimized
      technical parameters were determined by the contents of evodiamine and evodine.
      And the acute toxicity and pharmacodynamics were studied by rats. RESULT: The
      process was that the liquorice-processed fructus evodiae was wetted by liquorice
      decoction by sixth of raw fructus evodiae (V/W) and fried below 230 degrees C.
      The method of detecting the contents of evodiamine and evodine was that Alltima
      ODS C18 (4.6 mm x 250 mm, 5 microm); mobile phase acetonitrile-water
      tetrahydrofuran-phosphoric acid (51:48: 1: 0.05); column temperature 25 degrees
      C; mobile rate 0.8 mL x min(-1); wave length 225 nm. The toxicity experimentation
      show that rats didnt show any notable changes after affused the raw material and
      the processed fructus evodiae's decotion 40 g x kg(-1) b. w. at one time seven
      days constantly. The analgesic effect was observed after 0.6 g (material) x kg(
      1) (weight) b. w. CONCLUSION: The toxicity of the raw material and the processed
      one were low and the liquorice-processed fructus evodia analgesic effect was
      good.

PMID- 18619344
TI  - [Preparation and study in vitro of long-circulating nanoliposomes of curcumin].
AB  - OBJECTIVE: To prepare the long-circulating nanoliposomes of curcumin. METHOD: The
      long-circulating nanoliposomes were prepared by ethanol infusion and the
      encapsulation efficiency was determindated by the mini-column centrifugation. The
      effect of some factors on the encapsulation efficiency, such as the buffer
      solutions, the weight ratio of curcumin to SPC, the weight ratio of SPC to Chol,
      the pH of buffer solution and the iron strength of water phase, was investigated
      respectively. Then the formulation was optimized by orthogonal design. RESULT:
      The encapsulation efficiency of the curcumin liposomes was (88.27 +/- 2.16)%, and
      the average diameter of the liposomes was (136 +/- 18) nm. There was no change on
      encapsulation efficency within 30 d. CONCLUSION: The preparation of curcumin
      liposomes was easy and practicable and the pharmaceutical characterization showed
      that the curcumin liposomes are stable.

PMID- 18619345
TI  - [Effects of different drying methods and conditions on anthraquinones and tannins
      in water extract from Radix et Rhiroma Rhei].
AB  - OBJECTIVE: To investigate effects of different drying methods on the content of
      anthraquinones and tannins in water extract from Radix et Rhiroma Rhei (DHY).
      METHOD: DHY was dried by freeze drying, vacuum drying, drying under normal press
      and spray drying respectively until its moisture has been 5%. The content of
      anthraquinones and tannins of samples by different drying methods was determined
      and compared with. RESULT: The content of total anthraquinones, free
      anthraquinones, conjugated anthraquinones and tannins of samples by different
      drying methods was some different. Samples with freeze drying were highest and
      samples with drying under normal press at 100 degrees C were low. CONCLUSION:
      Temperature is an important pole in drying process water extract from Radix et
      Rhiroma Rhei. In our study water extract from Radix et Rhiroma Rhei was stable
      under 60 degrees C on the whole and unstable when drying exceed in 90 degrees C.

PMID- 18619347
TI  - [Studies on chemical constituents of Sarcandra glabra].
AB  - OBJECTIVE: To study antibacterial chemical constituents of Sarcandra glabra.
      METHOD: The constituents of the chloroform and EtOAc-soluble portions of the EtOH
      extract from the whole plant of S. glabra, which posses the antibacterial
      activities, were isolated and purified with column chromatography. The compounds
      were identified by physical and spectroscopic techniques. RESULT: Six compounds
      were isolated and identified as 4, 4'-biisofraxidin (1), esculetin (2), fraxetin
      (3), scoparone (4), isofraxidin (5), scopoletin(6), respectively. CONCLUSION:
      Compound 1 is a novel natural product. Compounds 24 were isolated from the plants
      of Chloranthaceae for the first time. The antibacterial activities of these six
      compounds were tested for the first time. Some compounds may have potential for
      future study and development as plant-derived oral antibacterial agents.

PMID- 18619346
TI  - [Optimizing extraction process of Scutellaria barbata by golden section method].
AB  - OBJECTIVE: To probe into the feasibility of golden section method in the
      optimization of the extraction process of Scutellaria barbata. METHOD: With the
      determination of the content of scutellarin and total flavonoids, selecting the
      range of alcohol concentration in the extraction of S. barbata was determined by
      the golden section method and method of equal interval, and validated it by
      orthogonal design. RESULT: The best extraction technique is that extract 3 times
      with 15 times of the alcohol which concentration is 70%, and each time for 1 h.
      CONCLUSION: Applying golden section method in the extraction of S. barbata is
      practical, which as a method of preliminary trial, indicates that golden section
      method can also be applied into the field of optimization of extraction process
      of traditional Chinese medicine.

PMID- 18619348
TI  - [A new flavonoid from heartwood of Caesalpinia sappan].
AB  - OBJECTIVE: To seek for new active components from Caesalpinia sappan. METHOD: The
      chemical constituents were isolated and identified by means of chromatographic
      and spectroscopic technologies methods. RESULT: Nine compounds were isolated, and
      their structures were identified as 3, 8-dihydroxy4, 10-dimethoxy-7-oxo-[2]
      benzopyrano[4,3-b] benzopyran (1), 3-deoxysappanchalcone (2), sappanchalcone (3),
      3-deoxysappanone B (4), rhamnetin (5), protosappanin C (6), 3, 7-dihydroxy
      chroman-4-one (7), dimethyl adipate (8), daucosterin (9). CONCLUSION: Compound 1
      was a new compound, and compounds 7, 8 were isolated from this plant for the
      first time.

PMID- 18619349
TI  - [Studies on chemical constituents from whole plants of Crossostephium chinense].
AB  - Eight compounds were isolated from the whole plants of Crossostephium chinense.
      Their structures were identified on the basis of analysis of spectral data. Eight
      compounds were taraxeryl acetate (1), taraxerol (2), alpha-amyrin acetate (3),
      beta-amyrin acetate (4), beta-sitosterol (5), 3beta-acetoxy-12-ursen-11-one (6),
      uracil (7) and 5-O-methyl-myo-inositol (8). Compounds 3-8 were isolated from the
      plant for the first time.

PMID- 18619350
TI  - [Studies on chemical constituents of Ranunculus ternatus].
AB  - OBJECTIVE: To study the active constituents of Ranunculus ternatus. METHOD: The
      constituents were isolated with silica gel and Sephadex LH -20 gel column
      chromatography and purified by HPLC. Their structures were elucidated by
      spectroscopy. RESULT: Sixteen compounds were obtained and identified as
      Stigmasta4, 6, 8 (14), 22-tetraen-3-one (1), 5-hydroxymethyl furaldehyde (2),
      gamma-keto-delta-valerolactone (3), pantolactone (4), 5-hydroxymethyl-dihydro
      furan-2-one (5), methyl 5-hydroxy-4-oxopentanoate (6), methyl hydrogen succinate
      (7), succinic acid monoethyl ester (8), 3, 4-dihydroxybenzoic acid methyl ester
      (9), p-hydroxycinnamic acid (10), 4-oxo-pentanoic acid (11), succinic acid (12),
      nonanedioic acid (13), 4-hydroxybenzoic acid (14), 4-hydroxybenzaldehyde (15),
      stigmasterol-3-O-beta-D-glucopyranoside (16). CONCLUSION: Compound 1, 4 -15 are
      obtained from this plant for the first time.

PMID- 18619351
TI  - [Study on adscription of drug constituents in Beagle dog plasma after
      intragastric administration with Jiangzhining extract].
AB  - OBJECTIVE: To investigate the drug constituents in Beagle dog plasma after
      intragastric administration with Jiangzhining extract, which is a Chinese
      medicine prescription and it consisting of processed Radix Polygoni Multiflori,
      Fructus Crataegi, Semen Cassiae and Folium Nelumbinis. METHOD: The drug
      constituents and their origin in Beagle dogs plasma were assigned by comparison
      of high-performance liquid chromatographic profiles, retention time and
      ultraviolet spectra of the drug-free plasma, plasma contained drug, Jiangzhining
      extract and the ingredients of crude drug. RESULT: Twenty-four components were
      detected after intragastric administration of Jiangzhining extract, among which
      eight compounds were the original components existed in Jiangzhining extract and
      sixteen compounds were likely to metabolites of the some chemical constituents in
      ingredients of crude drug. CONCLUSION: Studies on the drug constituents and the
      metabolites in plasma after intragastric administration of Jiangzhining extract
      are useful to elucidate the effective substances of Jiangzhining prescription.

PMID- 18619352
TI  - [Experimental study of saikosaponin-D (SSd) on lipid peroxidation of hepatic
      fibrosis on rat].
AB  - OBJECTIVE: To study the effect of SSd on lipid peroxidation during experimental
      hepatic fibrosis progression. METHOD: The experimental models of hepatic fibrosis
      were induced by intraperitoneal injection of dimethylnitrosamine (DMN) on rats.
      SSd was administered by intraperitoneal injection for 4 weeks. Serum was analyzed
      for alanine and aspartate aminotransferase (ALT and AST), hyaluronic acid (HA),
      laminin (LN), collagen IV (IV-C), malonaldehyde (MDA) and superoxide dismutase
      (SOD) activities. Liver samples were measured for MDA contents and SOD activities
      in normal group, model group and SSd group. RESULT: SSd significantly decreased
      ALT and AST activities and lowered HA, LN and IV-C contents. It enhanced SOD
      activities in liver, while reduced MDA contents both in serum and liver.
      CONCLUSION: SSd has obvious effects of protecting hepatocytes and resisting
      hepatic fibrosis, and the mechanism may be associated with its anti-lipid
      peroxidation effect.

PMID- 18619353
TI  - [Effects of 2, 3, 4', 5-tetrahydroxystilbene -2-O-beta-D glucoside on content of
      nitric oxide synthase and expression of nitric oxide synthase in artery vessels
      of experimental atherosclerotic rats].
AB  - OBJECTIVE: To investigate the effects of TSG on the content of nitric oxide
      synthase and the expression of endothelium nitric oxide synthase in artery
      vessels of experimental atherosclerotic rats. METHOD: The atherosclerosis model
      of rat was made by feeding high grease food and injecting Vit D3. Sixty male rats
      were randomly divided into six groups: normal control; model control; TSG high
      dose; TSG middle dose; TSG low dose; Simvastatin. After 12 weeks, several aorta
      were randomly tested, and the model made was successful when we found plaque. And
      after six weeks of treatment, the levels of NOS in serum were measured with a
      biochemical method. The biochemical method was adopted to detect the content of
      nitric oxide synthase and half-quantitative reverse transcription polymerase
      chain reaction (RT-PCR) was used to detect eNOS and iNOS gene expression in
      artery vessels. RESULT: Data of the study demonstrated that compared with model
      group, the activity of NOS and the gene expression of eNOS were increased
      remarkably, and however the gene expression of iNOS was reduced markedly in
      simvastatin group and TSG 60, 120 mg x kg(-1) x d(-1) group. CONCLUSION: TSG can
      enhance the expression of eNOS gene and reduce the expression of iNOS gene in
      aorta vessels of experimental atherosclerotic rats, which may be one of the anti
      atherosclerosis mechanisms of TSG.

PMID- 18619354
TI  - [Immunoregulatory activity of polysaccharopeptide and Astragalus polysaccharides
      on EAC tumor-bearing mice].
AB  - OBJECTIVE: To investigate the immunoregulatory activities of polysaccharopeptide
      and astragalus polysaccharides on EAC tumor-bearing mice. METHOD: Ehrlich's
      ascites carcinoma (EAC) Kunming (KM) mice were used to establish the animal model
      for solid tumor. Mice were randomly divided into six groups (n = 10): NS group
      (NS, 10 mL x kg(-1) x d(-1)), AMD group (AMD, 4 mg x kg(-1) x d(-1), 0.2 mL, only
      for the first 3 days), PSP group (PSP, 250 mg x kg(-1) x d(-1), 0.2 mL), APS
      group (APS, 250 mg x kg(-1) x d(-1), 0.2 mL), complex prescription group (PSP +
      APS, 250 mg x kg(-1) x d(-1), 0.1 mL) and combined treat group (AMD + PSP + APS,
      same dosage as above). After thirty days of treatment, immunocytochemical method
      was employed to detect the changes of T-lymphocyte subsets in the PBMC of tumor
      bearing mice. Subsequently, the organ indexes and tumor inhibition rate were
      calculated and compared with those of control group. RESULT: Percentage of CD3+,
      CD4+ T-cell and the ratio of CD4+/CD8+ were obviously prominence in the PSP and
      PSP + APS groups compared with those of NS group (0.05), percentage of CD8+ T
      cell was significantly decreased compared with that of AMD group; percentage of
      CD3+, CD4+ T-cell were obviously increased in AMD + PSP + APS group relative to
      that of AMD group; the thymus index of AMD group was significantly decreased
      compared with that of NS group, but the thymus index of AMD + PSP + APS group was
      obviously increased compared with that of AMD group; the weight of tumor in each
      administration group was significantly decreased compared with that of NS group.
      CONCLUSION: PSP and PSP + APS complex prescription showed the remarkable
      immunoregulation on EAC mice with chemotherapy or not.

PMID- 18619355
TI  - [Effects of rat serum containing total flavonoid extract of Epimedium sagittatum
      on development of osteoblasts].
AB  - OBJECTIVE: To investigate the effects of total flavonoid extract of Epimedium
      sagittatum (TFE) on the proliferation and differentiation of newborn rat
      calvarial osteoblasts (ROB). METHOD: TFE was supplemented into the culture medium
      of ROB at 0. 1, 1, 10 and 100 microg x mL(-1) respectively. The serum of rats
      administered TFES (SRAT) was also added into the medium in a parallel treatment
      at 2.5%, 5% and 10% respectively. Their effects on cell proliferation and
      differentiation was studied by MTT and the analysis of osteogenic differentiation
      marks. RESULT: TFE had no appreciable and on cell proliferation and
      differentiation at any concentration. However, 2.5% and 5% SRAT stimulated cell
      proliferation strongly and, 5% SRAT significantly promoted the maturation and
      function of osteoblast by improving the alkaline phosphatase activity,
      osteocalcin secretion, calcium deposition and the number of mineralized nodular
      structures. CONCLUSION: The metabolites of TFE should be the anti-osteoporosis
      constitutes of Epimedium sagittatum.

PMID- 18619356
TI  - [Neuroprotection and neurotrophism effects of liquiritin on primary cultured
      hippocampal cells].
AB  - OBJECTIVE: To observe the neuroprotective and neurotrophic effects ofliquiritin
      (LQ) on rats primary cultured hippocampal neuronal damage induced by Abeta25-35.
      METHOD: The rats hippocampal neuronal damage model by Abeta25-35 was established.
      The protective effects of LQ to the cells were observed through the MTU assay.
      The apoptosis of neurons was detected by flow cytometer and the concentration of
      intracellular calcium by fluorescence probe dying. LQ' s neurotrophic effects
      were observed through measuring the neurite outgrowth induced by LQ in primary
      cultured hippocampal neurons and the differentiation of LQ on hippocampal stem
      cells to cholinergic neurons was assayed by flow cytometry. RESULT: Treatment of
      the cells with 10 micromol x L(-1) Abeta25-35 could induce a significant decrease
      of cell viability, enhance the level of intracellular [Ca2+] and increase the
      percentage of apoptosis to 28%. However, pretreatment with LQ (0.1, 1, and 10
      micromol x L(-1)) for 6 hours exhibited cytoprotective effects, inhibited the
      cells' s death induced by Abeta25-35, prevented the accumulation of [Ca2+], and
      decreased the apoptosis neurons significantly to 10%, 15% and 9%, which meaned
      that LQ could antagonize Abeta25-35 induced apoptosis. LQ together with NGF had a
      dramatic prolonged effect on the neurite of the primary cultured hippocampal
      neurons, which was blocked by a specific MAPK kinase inhibitor to some extent. In
      addition, LQ could induce the differentiation of hippocampal stem cells to
      cholinergic neurons in vitro. CONCLUSION: These results demonstrate that LQ has
      the neuroprotective capacity to cell damage iduced by Abeta25-35 in primary
      cultured hippocampal neurons, and also has the neurotrophic effects.

PMID- 18619357
TI  - [Changes of c-fos, c-jun mRNA expressions in cardiomyocyte hypertrophy induced by
      angiotensin II and effects of tanshinone II A].
AB  - OBJECTIVE: To investigate the changes of proto-oncogene c-fos, c-jun mRNA
      expression in angiotensin II (Ang II)-induced hypertrophy and effects of
      tanshinone II A (Tan) in the primary culture of neonatal rat cardiomyocytes.
      METHOD: Twelve neonatal Wistar rats aged one day old of clean grade and both
      sexes were selected to isolate and culture cardiomyocytes. The cardiomyocytes
      were divided into: normal control group, Ang II (10(-6) mol x L(-1)) group, Ang
      II (10(-6) mol x L(-1)) +Tan (10(-8) g x L(-1)) group, Ang II (10(-6) mol x L(
      1)) + valsartan (10(-6) mol x L(-1)) group, Tan (10(-8) g x L(-1)) group,
      valsartan (10(-6) mol x L(-1)) group. The cardiomyocyte size was determined by
      phase contrast microscope, the rate of protein synthesis in cardiomyocytes was
      measured by 3H-leucine incorporation. The c-fos, c-jun mRNA expression of
      cardiomyocytes were assessed using reverse transcription polymerase chain
      reaction (RT-PCR). RESULT: Ang II was added to the culture medium and 30 min
      later, the c-fos, c-jun mRNA expression of cardiomyocytes increased significantly
      (P < 0. 01). After Ang II took effect for 24 h, the rate of protein synthesis in
      Ang II group increased more prominently than that in normal control group (P <
      0.01). After Ang II took effect for 7 days, the size of cardiomyocyte in Ang II
      group increased obviously (P < 0. 05). If tanshinone II or valsartan was added to
      the culture medium before Ang II, both of them could inhibit the increase of c
      fos, c-jun mRNA expression (P < 0.01), cardiomyocyte protein synthesis rate (P <
      0.01), and cardiomyocyte size (P < 0.05) induced by Ang II. CONCLUSION:
      Tanshinone II could ameliorate Ang II-induced cardiomyocytes hypertrophy by
      inhabiting c-fos, c-jun mRNA expression.

PMID- 18619358
TI  - [Inhibitory effect of sinomenine on H2O2-induced apoptosis in neonatal rat
      cardiomyocytes].
AB  - OBJECTIVE: To study the effects of sinomenine on apoptosis in cutured neonatal
      rat cardiomyocytes induced by H2O2 and its possible mechanism. METHOD: H2O2 was
      used to build an oxidative stress-induced injury model in neonatal rat
      cardiomyocytes after being treated with sinomenine (10, 30, 100 micromol L(-1)),
      the apoptosis rate, the content of malondialdehyde (MDA), the activity of
      superoxide dimutase (SOD), the activity of lactate dehydrogenase (LDH) and
      expression of NF-kappaB protein of the Cardiomyocytes were examined. RESULT:
      Compared with the model group, the apoptosis rate and the content of MDA, LDH
      decreased greatly (P < 0.01), and the activity of SOD increased distinctly (P <
      0.01) after being treated by sinomenine (10, 30, 100 micromol x L(-1)).
      CONCLUSION: Sinomenine can inhibit the apoptosis induced by H2O2 in neonatal rat
      cardiomyocytes. The protective mechanism could be related to its ability to
      reduce lipid pexosidation and to inhibit cardiomyocyte expression of NF-kappaB
      protein.

PMID- 18619359
TI  - [Therapeutic effect observation of bailing capsule and medical gymnastics to COPD
      in paracmasis].
AB  - OBJECTIVE: Discuss the therapeutic effect of Bailing capsule and the medical
      gymnastics (MG) to chronic obstructive pulmonary diseases (COPD) in paracmasis.
      METHOD: Adopt prospective study method that we divide 50 COPD patients into two
      group in random, the contrast group (25 patients) to treat by routine western
      medicine. The therapeutic group (25 patients) to treat by the Bailing capsule and
      the lung recovery medical gymnastics. After 6 months, we observe the patients'
      condition of lung ventilation, dyspneic respiration and disease resistance.
      RESULT: The therapeutic group is better than the contrast group obviously, the
      patients' condition of dyspneic respiration are improved, the descent rate of the
      average level of dyspneic respiration. The therapeutic group was 24.53%, the
      contrast group was 3.7%. The index of lung ventilation is all improved obviously
      (P < 0.05 or P < 0.01). The disease resistance of the therapeutic group is
      improved after the treat (P < 0.01). CONCLUSION: It is a good method to cure COPD
      in paracmasis by the traditional Chinese medicine Bailing capsule and the medical
      gymnastics, to the patients of insufficiency of QI of the lung and kidney
      especially, the method can improve the disease resistance and lung ventilation.

PMID- 18619360
TI  - [Progress of traditional Chinese medicine intervention after percutaneous
      coronary intervention].
AB  - Percutaneous coronary intervention has been the main effective method for
      coronary heart disease recently, but the post-operative complications became the
      main factors to limit its curative effect. Considering the understanding on
      traditional Chinese medicine (TCM) syndromes of post-interventional therapy and
      the advance of pharmaceutical research we suggest that evolution law of TCM
      syndrome types should be hold intensively and practical therapies and formulae
      should be established under the guidance of TCM basic theory.

PMID- 18619361
TI  - [Development of clinical application and experimental reseach on prescription
      biejiajian wan].
AB  - We reviewed the modern development of clinical application and experimental
      reseach on the prescription Biejiajian Wan (BJ), which are the basement that we
      will study its anti-renal fibrosis. At present, the prescription BJ is mainly
      applied to the treatment of chronic heptic desease. Its experimental reseach is
      mainly confined to the studing of anti-heptic fibrosi. Refering the scientific
      and technological result of anti-heptic fibrosis, we think the prescription BJ
      would have the effection of anti-renal fibrosis on the basis of theory of
      planning treatment according to diagnosis. But it has not been reported to the
      prescription BJ on the clinical and experimental reseach on anti-renal fibrosis.
      Therefore, it is very important to take on clinical reseach of the prescription
      BJ and discuss the effecting mechanism of anti-renal fibrosis from the level of
      integration, cell and molecule, which will help to enlarge the clinical
      application of the prescription Biejiajianwan and explained the essence of
      "persistent diseases injuring collateral branch of large channel" in traditional
      Chinese medicine.

PMID- 18619362
TI  - [Review of effervescent technique in pharmaceutics research].
AB  - Effervescent technique, which can accelerate drug disintegration and dissolution,
      is usually applied in quick release preparations. Along with the development of
      pharmaceutical technique and theory, effervescent technique is used more and more
      extensively to adjust the behavior of drug release, such as in sustained and
      controlled release preparations, pulsatile drug delivery systems, and so on. This
      review demonstrated the new applying of effervescent technique in effervescent
      tablets, stomach floating forms, osmotic pump tablets and pulsatile drug delivery
      systems, adding to the critical common technique of effervescent forms in drug
      research. This will be benefit for the further research and development of
      effervescent technique.

PMID- 18619363
TI  - [Study on application of low altitude remote sensing to Chinese herb medicinal
      sustainable utilization].
AB  - Sustainable utilization and bio-diversity protection of traditional Chinese
      medicine (TCM) have been a hotspot of the TCM study at present, in which the
      choice of appropriate method is one of the primary problems confronted. This
      paper described the technical system, equipment and image processing of low
      altitude remote sensing, and analyzed its future application in Chinese herb
      medicinal sustainable utilization.

PMID- 18619364
TI  - Viral interference in feline leukemia-sarcoma complex.
AB  - Feline leukemia viruses replicate in feline embryo fibroblast cultures without
      causing visible effects. The virus-infected cultures acquire a resistance to
      superinfection with the closely related focus-forming feline leukemia pseudotypes
      of murine sarcoma virus and the feline sarcoma viruses. This induction of viral
      interference in tissue cultures with the cell-transforming effects of the
      challenge viruses can be used as a quantitative in vitro assay for the detection
      of feline leukemia viruses. Preliminary observations indicate that the
      interference is virus strain-specific (type-specific) and suggest the existence
      of distinct differences in viral envelope characteristics demonstrable in the
      viral interference tests.

PMID- 18619365
TI  - Genetic control of the DNA maturation in the process of phage morphogenesis.

PMID- 18619367
TI  - Amantadine hydrochloride inhibition of early and late stages of lymphocytic
      choriomeningitis virus-cell interactions.
AB  - Amantadine hydrochloride inhibits the CA1371, UBC, and WE strains of LCM in both
      BHK21/13S and L-929 cells. The compound has no direct inactivating effect on
      virus infectivity nor does it affect the adsorption of virus to cells. By
      observing the susceptibility of cell-adsorbed virus to neutralizing antibody,
      amantadine was shown to delay virion penetration. Furthermore, addition of the
      drug at any time during ongoing viral replication, with all cells scoring as
      infective centers, inhibits virus synthesis and release.

PMID- 18619368
TI  - Characteristics of the structural components of the mouse mammary tumor virus.
      II. Viral proteins and antigens.
AB  - Mild Tween 80-ether treatment of mouse mammary tumor virus (MTV) results in
      disruption of the viral membrane and release of subviral components. Prolonged
      lipid extraction, however, results in virtually complete solubilization of the
      virion. Soluble proteins have been separated by Sephadex G-200 chromatography and
      used for immunization of rats These antisera identify five viral antigens
      (designated MTV-s1, s2, s3, s4, and s5). The s1 and s2 antigens are group
      specific, and are the antigens of the viral nucleoid. MTV-s3 antigen is a
      structural protein of the viral membrane. Poly-acrylamide gel electrophoresis of
      MTV shows five major polypeptides in the virion; the molecular weights of these
      are p1 (90,000), p2 (70,000), p3 (52,000), p4 (33,000), and p5 (23,000). The
      major protein of the virus is p3; it is found in the nucleoid and carries the s1
      antigen. Protein p5 is the structural protein of the membrane, and it carries the
      s3 antigen. Antisera prepared against isolated MTV proteins were used also in
      immunofluorescence tests to determine the intracellular deposition of MTV
      antigens. These studies show that all MTV structural proteins are synthesized
      cytoplasmically. Screening of a variety of neoplasms by immunofluorescence and
      immunodiffusion tests demonstrates MTV infection in only three types of
      neoplastic diseases, mammary tumors, ML+ leukemias, and Leydig cell tumors of MTV
      infected mice. Mammary tumors synthesize all viral structural proteins, while the
      synthesis of MTV proteins in the ML+ leukemias and Leydig cell tumor is limited
      to the s1 and s2 antigens. Electron microscopic examination of these tissues
      confirms the synthesis and accumulation of viral nucleocapsids (A particles)
      without the production of budding virions.

PMID- 18619369
TI  - Cell transformation induced by Rous sarcoma virus: analysis of density
      dependence.
AB  - Trypsinized chick embryo cells will divide at least once when seeded onto
      stationary, preexisting cultures of chick cells, but not when seeded onto
      stationary mouse cells. It is suggested that the mouse cells reconstitute a
      surface component for the trypsinized chick cells. These findings explain why
      crowded mouse cell layers, but not chick cell layers, suppress the transformation
      of chick cells infected with Rous sarcoma virus (RSV), since the infected cells
      must proceed through one cell cycle before transformation is expressed. Density
      dependent suppression of cell transformation by RSV is not related to the
      susceptibility of the inhibiting cell layer to infection with RSV. High cell
      density does not affect the adsorption and penetration of RSV but does affect the
      development of morphologically distinct foci of Rous cells. In cultures which are
      dense, aged, or maintained without agar overlay, morphological conversion is
      suppressed without concomitant suppression of transformed growth characteristics.
      In these conditions, therefore, morphological conversion is considered a poor
      index of neoplastic transformation induced by RSV.

PMID- 18619370
TI  - Genetic expression in bacteriophage lambda. IV. Effects of P2 prophage on lambda
      inhibition of host synthesis and lambda gene expression.
AB  - The effects of P2 prophage on lambda-mediated depression of host metabolism, and
      on lambda macromolecular synthesis have been studied. Experiments employing
      certain lambdabio deletion mutants and lambda-related phages suggest that the
      same gene products are involved in inhibition of host metabolism (Hin+ function)
      and susceptibility to P2 inhibition (Spi+ function). Synthesis of early lambda
      mRNA and protein occurs normally during the first 10 min after lambda infection
      of P2 lysogens, but subsequent expression of early and late lambda genes is
      interfered with by the combined actions of the P2 old gene and lambda Hin+ (Spi+)
      function. In addition, the P2 old+ product enhances the inhibitory effects of
      lambda Hin+ function on host metabolism, and can substitute for a component of
      this function lacking in lambdabio 72 and lambdabio 69.

PMID- 18619371
TI  - The nomenclature and classification of viruses the International Committee on
      Nomenclature of Viruses.

PMID- 18619372
TI  - Reaction of nitrous acid with viral nucleic acids in situ.

PMID- 18619373
TI  - Influenza viral RNA and ribonucleoprotein synthesized in abortive infection.

PMID- 18619374
TI  - Radiologic clinics of North America. Imaging of Lymphoma. Preface.

PMID- 18619375
TI  - Overview of lymphoma diagnosis and management.
AB  - The malignant lymphomas, including both Hodgkin lymphoma (HL) and non-Hodgkin
      lymphoma (NHL), represent a diverse group of diseases that arise from a clonal
      proliferation of lymphocytes. Each of the more than 30 unique types of lymphoma
      is a disease with a distinct natural history. This biologic heterogeneity gives
      rise to marked differences among the lymphomas with respect to epidemiology,
      pathologic characteristics, clinical presentation, and optimal management. This
      article emphasizes the principles of diagnosis, including appropriate pathologic
      evaluation and staging considerations, and focuses on the clinical presentation,
      staging, and optimal management strategies for the most common types of lymphoma.

PMID- 18619376
TI  - The impact of fluorodeoxyglucose-positron emission tomography in primary staging
      and patient management in lymphoma patients.
AB  - Fully diagnostic positron emission tomography (PET)/CT scans acquired during oral
      and intravenous contrast can be provided to patients and referring physicians in
      a single imaging session. Although FDG uptake varies, most low-grade lymphomas
      exhibit sufficient FDG avidity to also be staged reliably with FDG PET/CT. PET/CT
      imaging is more accurate for lymphoma staging than PET or CT alone and has
      substantial impact on patient management. This accurate whole-body glucose
      metabolic survey should serve as the baseline for subsequent treatment response
      evaluations. PET/CT has evolved to become the modality of choice for staging of
      nodal and extranodal lymphoma, for assessing therapeutic response, and for
      establishing patient prognosis.

PMID- 18619377
TI  - New staging and response criteria for non-Hodgkin lymphoma and Hodgkin lymphoma.
AB  - The International Harmonization Project developed recommendations for the use of
      positron emission tomography (PET) in managing patients who have lymphoma. It
      provided guidance as to the interpretation of fluorodeoxyglucose (FDG) PET and
      generated response definitions, incorporating metabolic imaging with the goal of
      improving interpretation of response and comparability among studies, leading to
      accelerated new agent development, more rapid availability of more effective
      therapies, and the enhancement of outcome for patients with lymphoma.

PMID- 18619378
TI  - PET imaging for response assessment in lymphoma: potential and limitations.
AB  - Fluorodeoxyglucose positron emission tomography (FDG-PET) is now considered the
      most accurate tool for the assessment of treatment response and prognosis in
      patients with Hodgkin lymphoma and aggressive non-Hodgkin lymphoma. This article
      discusses the potential and limitations of FDG-PET for response assessment in
      malignant lymphoma during chemotherapy (interim PET) and at the end of
      chemotherapy. Interim PET is used to predict the likelihood for a complete
      response at the end of such therapy. End-of-treatment PET aims to establish the
      completeness of response or the presence of residual viable tumor tissue. Until
      the results of ongoing clinical trials emerge over the next 5 years, interim PET
      should be considered investigational and should not be used for patient
      management outside of study protocols.

PMID- 18619379
TI  - Perspectives of molecular imaging and radioimmunotherapy in lymphoma.
AB  - Successful treatment of Hodgkin lymphomas and non-Hodgkin lymphomas depends on
      accurate staging and prognostic estimations, as well as evaluation of response to
      therapy as early after initiation as possible. We focus on several aspects of
      molecular imaging and therapy that affect the management of patients who have
      lymphoma. First, we review prior use of gallium-67 citrate for evaluation of
      lymphoma patients, mainly from a historical perspective, since it was the
      mainstream lymphoma functional imaging tracer for decades. Next, we review
      current clinical uses of 18F Fluoro-2-Deoxyglucose (18F FDG) PET and PET/CT for
      evaluation of lymphoma patients and use of radioimmunotherapy in lymphoma.
      Finally, we discuss advances in molecular imaging that may herald the next
      generation of PET radiotracers after 18F FDG.

PMID- 18619380
TI  - Cross-sectional evaluation of thoracic lymphoma.
AB  - In patients who have lymphoma, the presence and distribution of thoracic
      involvement is important in both tumor staging and treatment. Thoracic
      involvement in Hodgkin lymphoma (HL) is more common than in non-Hodgkin lymphoma
      (NHL). In HL, mediastinal lymphadenopathy with contiguous spread is a hallmark,
      and lung parenchymal involvement at the initial presentation is almost always
      associated with mediastinal lymphadenopathy. NHL is more heterogeneous and
      generally presents at a more advanced stage than HL. Most often, mediastinal
      involvement occurs as a disseminated or recurrent form of extrathoracic lymphoma.
      Bulky mediastinal disease with compression of adjacent structures can occur,
      particularly with high-grade subtypes of NHL and isolated lung disease without
      mediastinal lymphadenopathy can occur in contrast to HL.

PMID- 18619381
TI  - Imaging of abdominal lymphoma.
AB  - This article discusses the radiologic appearances of solid organ involvement with
      Hodgkin and non-Hodgkin lymphoma in the abdominopelvic region. The most common
      radiologic patterns of involvement are illustrated. The imaging characteristics
      of lymphomatous involvement of abdominal organs overlap with several other
      disorders and the specific features pertaining to lymphoma are highlighted. In
      patients who have known lymphomas, other important management considerations,
      such as staging, response to therapy, malignant transformation, and
      identification of recurrent disease, are also discussed. The emerging role of
      fluorodeoxyglucose positron emission tomography is briefly outlined.

PMID- 18619382
TI  - Imaging of gastrointestinal lymphoma.
AB  - The gastrointestinal (GI) tract contains the largest collection of lymphocytes
      anywhere in the body. GI lymphoma may arise at any site in the GI tract but
      typically involves the stomach and small bowel in cases of systemic disease. Most
      cases are non-Hodgkin B-cell type. Enteropathy-associated T cell lymphoma can
      complicate celiac disease. Less commonly, lymphoma may originate in the GI tract
      without systemic involvement. This sometimes occurs in response to chronic
      infections. This article discusses the role of imaging in detecting and staging
      GI tract lymphomas, using fluoroscopy and cross-sectional imaging, primarily CT.

PMID- 18619383
TI  - Imaging of pediatric lymphomas.
AB  - Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) represent 10% to 15% of all
      malignancies occurring in children younger than 20 years of age. Advances in
      cross-sectional imaging and the availability of positron emission tomography
      (PET) and PET-CT have had a major impact on imaging and management of pediatric
      patients. This article reviews the clinical features of lymphoma, focusing on the
      spectrum of imaging findings seen in diagnosis, staging, and follow-up of HL and
      NHL. Pediatric NHL has four major histologic subtypes: Burkitt lymphoma, diffuse
      large B-cell lymphoma, anaplastic large cell lymphoma, and lymphoblastic
      lymphoma. The most important subtype of HL is nodular sclerosis.

PMID- 18619384
TI  - Imaging of lymphoma of the central nervous system, spine, and orbit.
AB  - Lymphomas of the central nervous system, spine, and orbit consist of both
      systemic lymphomas and primary central nervous system lymphomas. This article
      addresses the typical imaging findings of lymphoma in both immunocompetent and
      immunocompromised patients, discusses the differential possibilities, and reviews
      the response criteria being used in clinical trials. Also described are metabolic
      imaging techniques with nuclear medicine and advanced MR imaging and how they can
      help improve the understanding of tumor biology.

PMID- 18619385
TI  - Imaging Hodgkin and non-Hodgkin lymphoma in the head and neck.
AB  - Hodgkin (HL) and non-Hodgkin lymphoma (NHL) involving the head and neck have many
      overlapping imaging features. Definitive diagnosis depends on histology, but
      imaging trends may help distinguish lymphoma from other common pathologic
      entities in the head and neck. CT is useful for staging and assessing bony
      involvement, whereas MR imaging is performed for soft tissue detail in extranodal
      disease, especially when there is transpatial disease or intracranial or
      intraspinal extension. Positron emission tomography has become an important part
      of staging and surveillance imaging and is particularly useful to distinguish
      posttreatment fibrosis and residual tumor.

PMID- 18619386
TI  - Imaging of lymphoma of the musculoskeletal system.
AB  - Imaging plays a crucial role in staging and the assessment of treatment response
      in patients who have lymphoma of the musculoskeletal system. This article reviews
      imaging features of lymphoma of bone, muscles, cutaneous, and subcutaneous
      tissue. At radiography, lymphoma of the bone is most commonly lytic, but the
      affected bone also can appear deceptively normal, even when a large tumor is
      present. At CT, lymphoma of muscle can be homogenous in attenuation, and it may
      not show contrast enhancement, making tumor detection more difficult. Post
      treatment changes often are encountered at MR imaging and positron emission
      tomography, and when considered in light of the patient's therapy regimen (eg,
      radiation therapy and granulocyte-colony stimulating factor), they usually can be
      differentiated from tumor. Post-treatment changes include diffuse FDG uptake in
      marrow after chemotherapy, indicating rebound of normal marrow, and MR imaging
      signal abnormalities that may persist for anywhere from a few months to years
      after treatment.

PMID- 18619387
TI  - Imaging of complications of hematopoietic stem cell transplantation.
AB  - Hematopoietic stem cell transplantation is increasingly used for treatment of
      malignant and nonmalignant disorders, genetic and immunologic disorders, and
      solid tumors. Although advances in immunosuppressive therapy and management of
      infections have improved long-term survival, transplant recipients remain at risk
      for a multitude of complications, many of which are serious and life threatening.
      Posttransplant complications may be classified either according to the organ
      system or according to the timeframe following transplantation. Complications may
      involve the chest, abdominopelvic organs, the central nervous system, or
      musculoskeletal tissues. This article reviews the various clinical and radiologic
      findings of key complications following hematopoietic stem cell transplantation
      and the pertinent differentiating factors.

PMID- 18619388
TI  - Imaging of late complications from mantle field radiation in lymphoma patients.
AB  - Hodgkin lymphoma is one of the most curable cancers because of its sensitivity to
      both radiation and several chemotherapy agents. Radical radiotherapy alone
      provided curative therapy for patients who had Hodgkin lymphoma as early as six
      decades ago. Yet, the radiation field included normal organs, such as breast
      tissue, thyroid, and coronary arteries, which were at risk for long-term
      complications. Dedicated imaging approaches have been developed to evaluate late
      radiation effects on these structures.

PMID- 18619389
TI  - On second order sensitivity for stage-based population projection matrix models.
AB  - In this paper we present a simple method for identifying life-history
      perturbations in population projection matrices that yield an accelerating
      population growth rate. Accelerating growth means that the dependence of the
      growth rate on the perturbation is convex. Convexity, when the second sensitivity
      of the growth rate is positive, is calculated using a new formula derived from
      the transfer function of the perturbed system. This formula is used to explore
      the relationship between stasis and growth probabilities from stage-structured
      population projection matrices.

PMID- 18619390
TI  - Individualism in plant populations: using stochastic differential equations to
      model individual neighbourhood-dependent plant growth.
AB  - We study individual plant growth and size hierarchy formation in an experimental
      population of Arabidopsis thaliana, within an integrated analysis that explicitly
      accounts for size-dependent growth, size- and space-dependent competition, and
      environmental stochasticity. It is shown that a Gompertz-type stochastic
      differential equation (SDE) model, involving asymmetric competition kernels and a
      stochastic term which decreases with the logarithm of plant weight, efficiently
      describes individual plant growth, competition, and variability in the studied
      population. The model is evaluated within a Bayesian framework and compared to
      its deterministic counterpart, and to several simplified stochastic models, using
      distributional validation. We show that stochasticity is an important determinant
      of size hierarchy and that SDE models outperform the deterministic model if and
      only if structural components of competition (asymmetry; size- and space
      dependence) are accounted for. Implications of these results are discussed in the
      context of plant ecology and in more general modelling situations.

PMID- 18619391
TI  - Evaluation of interdisciplinary and transdisciplinary research: a literature
      review.
AB  - Interdisciplinarity has become a widespread mantra for research, accompanied by a
      growing body of publications. Evaluation, however, remains one of the least
      understood aspects. This review of interdisciplinary and transdisciplinary
      research evaluation categorizes lessons from the emergent international
      literature on the topic reviewed in 2007. It defines parallels between research
      performance and evaluation, presents seven generic principles for evaluation, and
      reflects in the conclusion on changing connotations of the underlying concepts of
      discipline, peer, and measurement. Interdisciplinary and transdisciplinary
      research performance and evaluation are both generative processes of harvesting,
      capitalizing, and leveraging multiple expertise. Individual standards must be
      calibrated, and tensions among different disciplinary, professional, and
      interdisciplinary approaches carefully managed in balancing acts that require
      negotiation and compromise. Readiness levels are strengthened by antecedent
      conditions that are flexible enough to allow multiple pathways of integration and
      collaboration. In both cases, as well, new epistemic communities must be
      constructed and new cultures of evidence produced. The multidisciplinary
      interdisciplinary-transdisciplinary research environment spans a wide range of
      contexts. Yet seven generic principles provide a coherent framework for thinking
      about evaluation: (1) variability of goals; (2) variability of criteria and
      indicators; (3) leveraging of integration; (4) interaction of social and
      cognitive factors in collaboration; (5) management, leadership, and coaching; (6)
      iteration in a comprehensive and transparent system; and (7) effectiveness and
      impact.

PMID- 18619392
TI  - Enhancing transdisciplinary research through collaborative leadership.
AB  - Transcending the well-established and familiar boundaries of disciplinary silos
      poses challenges for even the most interpersonally competent scientists. This
      paper explores the challenges inherent in leading transdisciplinary projects,
      detailing the critical roles that leaders play in shepherding transdisciplinary
      scientific endeavors. Three types of leadership tasks are considered: cognitive,
      structural, and processual. Distinctions are made between leading small, co
      located projects and large, dispersed ones. Finally, social-network analysis is
      proposed as a useful tool for conducting research on leadership, and, in
      particular, on the role of brokers, on complex transdisciplinary teams.

PMID- 18619393
TI  - Transdisciplinary training: key components and prerequisites for success.
AB  - The training of transdisciplinary science is distinct in its intention to develop
      scientists who synthesize the theoretical and methodologic approaches of
      different disciplines. As a result, transdisciplinary scientists are better
      prepared to address the complexities of health problems. The most common form of
      transdisciplinary training is the multi-mentor apprenticeship model, with each
      mentor training from his or her own discipline. The transdisciplinary trainee is
      faced with many challenges, including learning the languages and cultures of
      different disciplines along with learning how to navigate within and between
      disciplines. The trainee also confronts unique career development risks. The
      climb up the academic ladder can be slower, rougher, and less linear than that of
      the trainee's single-disciplinary-trained peers. A number of factors can help the
      trainee in overcoming the challenges: being able to develop a core set of values
      and behaviors that are essential for transdisciplinary scientists; having the
      commitment and support of training institutions, training directors, and mentors;
      and having training structures and processes in place to prevent the training and
      trainee from naturally regressing back to familiar single-disciplinary
      approaches. There is relatively little known empirically about transdisciplinary
      training. Future efforts can focus on developing a better understanding of the
      unique characteristics of transdisciplinary training, identifying the effective
      elements that relate to training outcomes, defining the critical outcome metrics
      at different time points during and following training, and creating toolkits to
      help with training processes.

PMID- 18619394
TI  - The social determinants of cancer: a challenge for transdisciplinary science.
AB  - To make further significant advances in cancer control research, a
      transdisciplinary science approach is needed that integrates the study of the
      biological nature of cancer and its clinical applications with the behavioral and
      social influences on cancer. More-effective interventions to reduce the burden of
      cancer can be developed and implemented by the adoption of a transdisciplinary
      research framework that takes into account the social determinants of cancer and
      seeks to discover interactions among social, environmental, behavioral, and
      biological factors in cancer etiology. This paper addresses two critical issues
      in the science of team science: (1) a cross-disciplinary, multilevel framework
      for organizing future research, and (2) a perspective that could aid in the
      translation and dissemination of cancer research findings in health care and
      public health practice. This conceptual framework is designed to encourage
      transdisciplinary research that will integrate social determinants into cancer
      research. The authors' goal is to promote a more complete understanding of the
      causes of cancer that will lead to the improved translation and implementation of
      the results of research.

PMID- 18619395
TI  - Measuring collaboration and transdisciplinary integration in team science.
AB  - PURPOSE: As the science of team science evolves, the development of measures that
      assess important processes related to working in transdisciplinary teams is
      critical. Therefore, the purpose of this paper is to present the psychometric
      properties of scales measuring collaborative processes and transdisciplinary
      integration. METHODS: Two hundred-sixteen researchers and research staff
      participating in the Transdisciplinary Tobacco Use Research Centers (TTURC)
      Initiative completed the TTURC researcher survey. Confirmatory-factor analyses
      were used to verify the hypothesized factor structures. Descriptive data
      pertinent to these scales and their associations with other constructs were
      included to further examine the properties of the scales. RESULTS: Overall, the
      hypothesized-factor structures, with some minor modifications, were validated. A
      total of four scales were developed, three to assess collaborative processes
      (satisfaction with the collaboration, impact of collaboration, trust and respect)
      and one to assess transdisciplinary integration. All scales were found to have
      adequate internal consistency (i.e., Cronbach alpha's were all >0.70); were
      correlated with intermediate markers of collaborations (e.g., the collaboration
      and transdisciplinary-integration scales were positively associated with the
      perception of a center's making good progress in creating new methods, new
      science and models, and new interventions); and showed some ability to detect
      group differences. CONCLUSIONS: This paper provides valid tools that can be
      utilized to examine the underlying processes of team science--an important step
      toward advancing the science of team science.

PMID- 18619396
TI  - The collaboration readiness of transdisciplinary research teams and centers
      findings from the National Cancer Institute's TREC Year-One evaluation study.
AB  - Growing interest in promoting cross-disciplinary collaboration among health
      scientists has prompted several federal agencies, including the NIH, to establish
      large, multicenter initiatives intended to foster collaborative research and
      training. In order to assess whether these initiatives are effective in promoting
      scientific collaboration that ultimately results in public health improvements,
      it is necessary to develop new strategies for evaluating research processes and
      products as well as the longer-term societal outcomes associated with these
      programs. Ideally, evaluative measures should be administered over the entire
      course of large initiatives, including their near-term and later phases. The
      present study focuses on the development of new tools for assessing the readiness
      for collaboration among health scientists at the outset (during the first year)
      of their participation in the National Cancer Institute's Transdisciplinary
      Research on Energetics and Cancer (TREC) initiative. Indexes of collaborative
      readiness, along with additional measures of near-term collaborative processes,
      were administered as part of the TREC Year-One evaluation survey. Additionally,
      early progress toward scientific collaboration and integration was assessed,
      using a protocol for evaluating written research products. Results from the Year
      One survey and the ratings of written products provide evidence of cross
      disciplinary collaboration among participants during the first year of the
      initiative, and also reveal opportunities for enhancing collaborative processes
      and outcomes during subsequent phases of the project. The implications of these
      findings for future evaluations of team science initiatives are discussed.

PMID- 18619397
TI  - Transdisciplinarity among tobacco harm-reduction researchers: a network analytic
      approach.
AB  - Progress in tobacco control and other areas of health research is thought to be
      heavily influenced by the extent to which researchers are able to work with each
      other not only within, but also across disciplines. This study provides an
      examination of the extent to which researchers in the area of tobacco harm
      reduction work together. Specifically, data were collected in 2005 from a
      national group of 67 top tobacco-control researchers from eight broadly defined
      disciplines representing 17 areas of expertise. Network analysis was utilized to
      examine the extent to which these researchers were engaged in research that was
      interdisciplinary or transdisciplinary, based on the outcome or product attained.
      Findings revealed that interdisciplinary network ties were much denser than
      transdisciplinary ties, but researchers in some disciplines were more likely to
      work across disciplines than others, especially when synergistic outcomes
      resulted. The study demonstrates for the first time how tobacco-control
      researchers work together, providing direction for policy officials seeking to
      encourage greater transdisciplinarity. The study also demonstrates the value of
      network-analysis methods for understanding research relationships in one
      important area of health care.

PMID- 18619398
TI  - Challenges for multilevel health disparities research in a transdisciplinary
      environment.
AB  - Numerous factors play a part in health disparities. Although health disparities
      are manifested at the level of the individual, other contexts should be
      considered when investigating the associations of disparities with clinical
      outcomes. These contexts include families, neighborhoods, social organizations,
      and healthcare facilities. This paper reports on health disparities research as a
      multilevel research domain from the perspective of a large national initiative.
      The Centers for Population Health and Health Disparities (CPHHD) program was
      established by the NIH to examine the highly dimensional, complex nature of
      disparities and their effects on health. Because of its inherently
      transdisciplinary nature, the CPHHD program provides a unique environment in
      which to perform multilevel health disparities research. During the course of the
      program, the CPHHD centers have experienced challenges specific to this type of
      research. The challenges were categorized along three axes: sources of subjects
      and data, data characteristics, and multilevel analysis and interpretation. The
      CPHHDs collectively offer a unique example of how these challenges are met; just
      as importantly, they reveal a broad range of issues that health disparities
      researchers should consider as they pursue transdisciplinary investigations in
      this domain, particularly in the context of a large team science initiative.

PMID- 18619399
TI  - The science of team science: commentary on measurements of scientific readiness.

PMID- 18619400
TI  - Systems thinking to improve the public's health.
AB  - Improving population health requires understanding and changing societal
      structures and functions, but countervailing forces sometimes undermine those
      changes, thus reflecting the adaptive complexity inherent in public health
      systems. The purpose of this paper is to propose systems thinking as a conceptual
      rubric for the practice of team science in public health, and transdisciplinary,
      translational research as a catalyst for promoting the functional efficiency of
      science. The paper lays a foundation for the conceptual understanding of systems
      thinking and transdisciplinary research, and will provide illustrative examples
      within and beyond public health. A set of recommendations for a systems-centric
      approach to translational science will be presented.

PMID- 18619401
TI  - The role of transdisciplinary collaboration in translating and disseminating
      health research: lessons learned and exemplars of success.
AB  - In the past few decades, significant advances have been made related to
      understanding, preventing, and treating chronic disease. Given these many
      advances across multiple disciplines, it is unclear why the potential for
      yielding substantial reduction in disease has not been achieved overall and
      across various subgroups. Socioeconomic and racial/ethnic disparities in a wide
      range of disease outcomes persist, and a number of studies highlight the
      importance of further improving behavioral risk-factor prevalence on a population
      level. The goal of this paper is to explore the role of transdisciplinary
      collaboration in the translation of research related to these vexing public
      health problems, and, in particular, to explore factors that appear to facilitate
      effective and sustainable translation. Transdisciplinary collaboration also has
      great potential to speed the rate of adoption of evidence-based practices.
      Examples of transdisciplinary collaborations in academic and community settings
      are provided, along with factors that may influence the long-term outcomes of
      transdisciplinary efforts.

PMID- 18619402
TI  - Interdisciplinarity and systems science to improve population health: a view from
      the NIH Office of Behavioral and Social Sciences Research.
AB  - Fueled by the rapid pace of discovery, humankind's ability to understand the
      ultimate causes of preventable common disease burdens and to identify solutions
      is now reaching a revolutionary tipping point. Achieving optimal health and well
      being for all members of society lies as much in the understanding of the factors
      identified by the behavioral, social, and public health sciences as by the
      biological ones. Accumulating advances in mathematical modeling, informatics,
      imaging, sensor technology, and communication tools have stimulated several
      converging trends in science: an emerging understanding of epigenomic regulation;
      dramatic successes in achieving population health-behavior changes; and improved
      scientific rigor in behavioral, social, and economic sciences. Fostering stronger
      interdisciplinary partnerships to bring together the behavioral-social-ecologic
      models of multilevel "causes of the causes" and the molecular, cellular, and,
      ultimately, physiological bases of health and disease will facilitate
      breakthroughs to improve the public's health. The strategic vision of the Office
      of Behavioral and Social Sciences Research (OBSSR) at the National Institutes of
      Health (NIH) is rooted in a collaborative approach to addressing the complex and
      multidimensional issues that challenge the public's health. This paper describes
      OBSSR's four key programmatic directions (next-generation basic science,
      interdisciplinary research, systems science, and a problem-based focus for
      population impact) to illustrate how interdisciplinary and transdisciplinary
      perspectives can foster the vertical integration of research among biological,
      behavioral, social, and population levels of analysis over the lifespan and
      across generations. Interdisciplinary and multilevel approaches are critical both
      to the OBSSR's mission of integrating behavioral and social sciences more fully
      into the NIH scientific enterprise and to the overall NIH mission of utilizing
      science in the pursuit of fundamental knowledge about the nature and behavior of
      living systems and the application of that knowledge to extend healthy life and
      reduce the burdens of illness and disability.

PMID- 18619403
TI  - Toward transdisciplinary research: historical and contemporary perspectives.
AB  - Over the past two decades a variety of national and international efforts has
      sought to bring together health and social scientists to address complex health
      issues. This paper reviews how the notion of transdisciplinary research has
      emerged; discusses research programs that have successfully traversed discipline
      boundaries in sustained fashion; considers facilitating and constraining factors
      that have emerged from the analyses of this process; and suggests next steps for
      conceptualizing, organizing, and assessing transdisciplinary research based on
      the notion of heterarchy.

PMID- 18619404
TI  - Of mice and mentors: developing cyber-infrastructure to support transdisciplinary
      scientific collaboration.

PMID- 18619405
TI  - Toward cross-sectoral team science.

PMID- 18619406
TI  - Moving the science of team science forward: collaboration and creativity.
AB  - Teams of scientists representing diverse disciplines are often brought together
      for purposes of better understanding and, ultimately, resolving urgent public
      health and environmental problems. Likewise, the emerging field of the science of
      team science draws on diverse disciplinary perspectives to better understand and
      enhance the processes and outcomes of scientific collaboration. In this
      supplement to the American Journal of Preventive Medicine, leading scholars in
      the nascent field of team science have come together with a common goal of
      advancing the field with new models, methods, and measures. This summary article
      highlights key themes reflected in the supplement and identifies several
      promising directions for future research organized around the following broad
      challenges: (1) operationalizing cross-disciplinary team science and training
      more clearly; (2) conceptualizing the multiple dimensions of readiness for team
      science; (3) ensuring the sustainability of transdisciplinary team science; (4)
      developing more effective models and strategies for training transdisciplinary
      scientists; (5) creating and validating improved models, methods, and measures
      for evaluating team science; and (6) fostering transdisciplinary cross-sector
      partnerships. A call to action is made to leaders from the research, funding, and
      practice sectors to embrace strategies of creativity and innovation in a
      collective effort to move the field forward, which may not only advance the
      science of team science but, ultimately, public health science and practice.

PMID- 18619407
TI  - The science of team science: overview of the field and introduction to the
      supplement.
AB  - The science of team science encompasses an amalgam of conceptual and methodologic
      strategies aimed at understanding and enhancing the outcomes of large-scale
      collaborative research and training programs. This field has emerged rapidly in
      recent years, largely in response to growing concerns about the cost
      effectiveness of public- and private-sector investments in team-based science and
      training initiatives. The distinctive boundaries and substantive concerns of this
      field, however, have remained difficult to discern. An important challenge for
      the field is to characterize the science of team science more clearly in terms of
      its major theoretical, methodologic, and translational concerns. The articles in
      this supplement address this challenge, especially in the context of designing,
      implementing, and evaluating cross-disciplinary research initiatives. This
      introductory article summarizes the major goals and organizing themes of the
      supplement, draws links between the constituent articles, and identifies new
      areas of study within the science of team science.

PMID- 18619408
TI  - The National Cancer Institute's transdisciplinary centers initiatives and the
      need for building a science of team science.

PMID- 18619409
TI  - The science of team science: assessing the value of transdisciplinary research.

PMID- 18619410
TI  - The ecology of team science: understanding contextual influences on
      transdisciplinary collaboration.
AB  - Increased public and private investments in large-scale team science initiatives
      over the past two decades have underscored the need to better understand how
      contextual factors influence the effectiveness of transdisciplinary scientific
      collaboration. Toward that goal, the findings from four distinct areas of
      research on team performance and collaboration are reviewed: (1) social
      psychological and management research on the effectiveness of teams in
      organizational and institutional settings; (2) studies of cyber-infrastructures
      (i.e., computer-based infrastructures) designed to support transdisciplinary
      collaboration across remote research sites; (3) investigations of community-based
      coalitions for health promotion; and (4) studies focusing directly on the
      antecedents, processes, and outcomes of scientific collaboration within
      transdisciplinary research centers and training programs. The empirical
      literature within these four domains reveals several contextual circumstances
      that either facilitate or hinder team performance and collaboration. A typology
      of contextual influences on transdisciplinary collaboration is proposed as a
      basis for deriving practical guidelines for designing, managing, and evaluating
      successful team science initiatives.

PMID- 18619411
TI  - Phospho-proteomic approach to identify new targets of leucine deprivation in
      muscle cells.
AB  - The aim of this study was to optimize a protocol that allows identifying changes
      at the phosphorylation level of specific proteins in response to cell stimulation
      by leucine starvation. To make possible the identification of differentially
      phosphorylated proteins by the combination of two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS), we prepared fraction enriched in
      phosphoproteins. For that purpose, we adapted the immobilized metal affinity
      chromatography (IMAC) technique to make it compatible with 2D-PAGE. On the whole,
      this procedure allowed identifying regulated targets of leucine deprivation:
      molecular chaperones glucose-regulated protein 58 kDa (GRP58) and BiP (GRP78),
      RNA helicase DEAD box polypeptide 3, and eukaryotic translation initiation factor
      4B (eIF4B).

PMID- 18619412
TI  - Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway.
AB  - Leptin (Ob), the peripheral signal produced by the adipocyte to regulate energy
      metabolism, can also be produced by placenta, where it may work as an autocrine
      hormone. Recently, we have demonstrated that leptin promotes proliferation and
      survival of trophoblastic cells. In the present work we aimed to study the signal
      transduction pathways that mediate the trophic effect of leptin in placenta, by
      using the human placenta choriocarcinoma JEG-3 cell line, as well as
      trophoblastic cells from human placenta. We have assayed the early phase of
      apoptosis, triggered by serum deprivation, by using Annexin V-propidium iodide
      (PI) labeling and flow cytometric analysis, as well as the late phase of
      apoptosis by studying the activation of caspase-3. We have studied the major
      signalling pathways known to be triggered by the leptin receptor, and we have
      investigated the relative importance of these pathways in the effect of leptin by
      using pharmacological inhibitors. We have found that leptin stimulates Janus
      kinase (JAK)-signal transducers and activators of transcription (STAT) pathway by
      promoting JAK-2 and STAT-3 tyrosine phosphorylation. We have also demonstrated
      the activation of mitogen-activated protein kinase (MAPK) pathway by studying
      phosphorylation of extracellular-signal regulated kinase (Erk) kinase (MEK) and
      Erk1/2. PI3K pathway is also triggered by leptin stimulation as assessed by the
      study of protein kinase B (PKB) phosphorylation. These signaling pathways were
      confirmed in trophoblastic cells obtained from placenta of healthy donors. The
      effect of leptin on JEG-3 survival was completely reversed by blocking Erk1/2
      activation employing the MEK inhibitor PD98059, whereas it was not affected by
      PI3K inhibition using wortmannin. These data suggest that the leptin
      antiapoptotic effect in placenta is mediated by the MAPK pathway.

PMID- 18619413
TI  - Functional ABCG1 expression induces apoptosis in macrophages and other cell
      types.
AB  - The expression of the ATP-binding cassette transporter ABCG1 is greatly increased
      in macrophages by cholesterol loading via the activation of the nuclear receptor
      LXR. Several recent studies demonstrated that ABCG1 expression is associated with
      increased cholesterol efflux from macrophages to high-density lipoprotein,
      suggesting an atheroprotective role for this protein. Our present study uncovers
      an as yet not described cellular function of ABCG1. Here we demonstrate that
      elevated expression of human ABCG1 is associated with apoptotic cell death in
      macrophages and also in other cell types. We found that overexpression of the
      wild type protein results in phosphatidyl serine (PS) translocation, caspase 3
      activation, and subsequent cell death, whereas neither the inactive mutant
      variant of ABCG1 (ABCG1K124M) nor the ABCG2 multidrug transporter had such
      effect. Induction of ABCG1 expression by LXR activation in Thp1 cells and in
      human monocyte-derived macrophages was accompanied by a significant increase in
      the number of apoptotic cells. Thyroxin and benzamil, previously identified
      inhibitors of ABCG1 function, selectively prevented ABCG1-promoted apoptosis in
      transfected cells as well as in LXR-induced macrophages. Collectively, our
      results suggest a causative relationship between ABCG1 function and apoptotic
      cell death, and may offer new insights into the role of ABCG1 in atherogenesis.

PMID- 18619414
TI  - Selection of IgE-binding aptameric green fluorescent protein (Ap-GFP) by the
      ribosome display (RD) platform.
AB  - GFP-Ckappa fusion protein was previously shown selectable on ribosome display
      platform with solid phase antibodies against GFP determinant [Y.-M. Yang, T.J.
      Barankiewicz, M. He, M. Taussig, S.-S. Chen, Selection of antigenic markers on a
      GFP-Ckappa fusion scaffold with high sensitivity by eukaryotic ribosome display,
      Biochem. Biophys. Res. Commun. 359 (2007) 251-257]. Herein, we show that members
      of aptameric peptide library constructed within the site 6 and site 8/9 loops of
      GFP of the ribosome display construct are selectable upon binding to the solid
      phase IgE antigen. An input of 1.0 microg of the dual site aptameric GFP library
      exhibiting a diversity of 7.5x10(11) was transcribed, translated and incubated
      with solid phase IgE. RT-PCR products were amplified from mRNA of the aptamer
      ribosome-mRNA (ARM) complex captured on the solid phase IgE. Clones of aptameric
      GFP were prepared from RT-PCR product of ARM complex following repetitive
      selection. Recombinant aptameric GFP proteins from the selected clones bind IgE
      coated on the 96-well plate, and the binding was abrogated by incubation with
      soluble human IgE but not human IgG. Selected aptameric GFP proteins also exhibit
      binding to three different sources of human IgE (IgE PS, BED, and JW8) but not
      irrelevant proteins. These observations indicate that appropriately selected
      aptameric GFP on a solid phase ligand by ribosome display may serve as an
      affinity reagent for blocking reactivity of a biological ligand.

PMID- 18619415
TI  - Murine Muller cells are progenitor cells for neuronal cells and fibrous tissue
      cells.
AB  - Mammalian Muller cells have been reported to possess retinal progenitor cell
      properties and generate new neurons after injury. This study investigates murine
      Muller cells under in vitro conditions for their capability of dedifferentiation
      into retinal progenitor cells. Muller cells were isolated from mouse retina, and
      proliferating cells were expanded in serum-containing medium. For
      dedifferentiation, the cultured cells were transferred to serum-replacement
      medium (SRM) at different points in time after their isolation. Interestingly,
      early cell passages produced fibrous tissue in which extracellular matrix
      proteins and connective tissue markers were differentially expressed. In
      contrast, aged Muller cell cultures formed neurospheres in SRM that are
      characteristic for neuronal progenitor cells. These neurospheres differentiated
      into neuron-like cells after cultivation on laminin/ornithine cell culture
      substrate. Here, we report for the first time that murine Muller cells can be
      progenitors for both, fibrous tissue cells and neuronal cells, depending on the
      age of the cell culture.

PMID- 18619416
TI  - N-Glycosylation is required for Na+-dependent vitamin C transporter
      functionality.
AB  - The human sodium-dependent vitamin C transporters (hSVCT1 and hSVCT2) mediate
      cellular uptake of ascorbic acid. Both these transporters contain potential sites
      for N-glycosylation in their extracellular domains (Asn-138, Asn-144 [hSVCT1];
      Asn-188, Asn-196 [hSVCT2]), however the role of N-glycosylation in transporter
      function is unexplored. On the basis of the result that tunicamycin decreased
      (14)C-ascorbic acid uptake in HepG2 cells, we systematically ablated all
      consensus N-glycosylation sites in hSVCT1 and hSVCT2 to resolve any effects on
      ascorbic acid uptake, transporter expression and targeting. We show that removal
      of individual N-glycosylation sites significantly impairs protein expression and
      consequently ascorbic acid uptake for hSVCT1 mutants (N138Q is retained
      intracellularly) and for hSVCT2 mutants (all of which reach the cell surface). N
      Glycosylation is therefore essential for vitamin C transporter functionality.

PMID- 18619417
TI  - Different inhibitory response of cyanidin and methylene blue for filament
      formation of tau microtubule-binding domain.
AB  - One of the priorities in Alzheimer research is to develop a compound that
      inhibits the filament formation of tau protein. Since the three- or four-repeat
      microtubule-binding domain (MBD) in tau protein plays an essential role in
      filament formation, the inhibitory behavior of cyanidin (Cy) and methylene blue
      (MB) with respect to heparin-induced filament formation of MBD in a neutral
      solution (pH 7.6) was characterized by fluorescence, circular dichroism, and
      electron microscopy measurements. The planar aromatic ring of Cy and the N
      unsubstituted phenothiazine ring of MB were shown to be necessary for the
      inhibition. However, the inhibitory responses with respect to heparin-induced
      filament formation to the second and third repeat peptides of MBD were different:
      Cy suppresses the formation and MB does not prevent the formation. This suggests
      the importance of the first and fourth repeat peptides in the inhibitory activity
      of MB for MBD filament formation. In this study, we showed that the decrease of
      thioflavin S fluorescence intensity is not always linked to inhibition of
      filament formation.

PMID- 18619418
TI  - Morphine and propranolol co-administration impair consolidation of Y-maze spatial
      recognition memory.
AB  - In the present study, the interaction between morphine and the beta-adrenergic
      receptor antagonist, propranolol (PROP), in memory consolidation was investigated
      in a two-trial recognition Y-maze task. Four sets of Y-maze experiments were
      carried out in mice, with 2 and 4 h inter-trial intervals (ITI) and all drugs
      administered immediately after the training trials. In the first and second sets
      of experiments, post-training administration of morphine (0.25 and 2.5 mg/kg) or
      PROP (2, 10 and 20 mg/kg) alone did not impair memory consolidation after a 2 h
      ITI. However, in the third and fourth sets of experiments, co-administration of
      these ineffective doses of morphine (0.25 and 2.5 mg/kg) and PROP (2, 10 and 20
      mg/kg) disrupted memory consolidation after a 2 h ITI. Moreover, the relatively
      higher dose of morphine (2.5 mg/kg) plus the relatively higher doses of PROP (10
      and 20 mg/kg) disrupted memory consolidation to a greater extent after a 2 h ITI.
      Locomotor activity was not affected by any of the drug treatments. Our data shows
      that morphine and PROP co-administration disrupts the consolidation of spatial
      recognition memory, suggesting that inactivation of the beta-adrenergic system
      may contribute to morphine-induced impairment of memory.

PMID- 18619419
TI  - Inability of volatile anesthetics to inhibit oxygen-glucose deprivation-induced
      glutamate release via glutamate transporters and anion channels in rat
      corticostriatal slices.
AB  - Ischemia-induced extracellular glutamate accumulation and the subsequent
      excitotoxicity contribute significantly to ischemic brain injury. Volatile
      anesthetics have been shown to reduce ischemic brain injury. Here, we showed that
      oxygen-glucose deprivation (OGD, to simulate ischemia in vitro) increased
      extracellular glutamate accumulation in the corticostriatal slices of adult rats.
      This increased accumulation was reduced by dihydrokinate, a glutamate transporter
      type 2 inhibitor, and 4,4'-dinitrostilbene-2,2'-disulfonic acid, a blocker for
      volume-activated anion channels. The volatile anesthetics isoflurane, sevoflurane
      and desflurane at clinically relevant concentrations did not affect the OGD
      induced extracellular glutamate accumulation from brain slices of adult rats.
      Isoflurane also did not change the OGD-induced extracellular glutamate
      accumulation from brain slices of newborn/young rats. These results suggest that
      the OGD-induced glutamate accumulation involves reversed transport of glutamate
      via glutamate transporters and volume-activated anion channels. Volatile
      anesthetics may not inhibit this extracellular glutamate accumulation.

PMID- 18619420
TI  - A deeper reanalysis of a superficial feature: an ERP study on agreement
      violations.
AB  - A morphosyntactic agreement violation during reading elicits a well-documented
      biphasic ERP pattern (LAN+P600). The cognitive variables that affect both the
      amplitude of the two components and the topography of the anterior negativity are
      still debated. We studied the ERP correlates of the violation of a specific
      agreement feature based on the phonology of the critical word. This was compared
      with the violation of a lexical feature, namely grammatical gender. These two
      features are different both in the level of representation involved in the
      agreement computation and in terms of their role in establishing structural
      relations with possible following constituents. The ERP pattern elicited by the
      two agreement violations showed interesting dissociations. The LAN was
      distributed ventrally for both types of violation, but showed a central extension
      for the gender violation. The P600 showed an amplitude modulation: this component
      was larger for phonotactic violations in its late time window (700-900 ms). The
      former result is indicative of a difference in the brain structures recruited for
      the processing of violations at different levels of representation. The P600
      effect is interpreted assuming a hierarchical relation among features that forces
      a deeper reanalysis of the violation involving a word form property. Finally the
      two features elicit distinct end-of-sentence wrap-up effects, consistent with the
      different roles they play in the processing of the whole sentence.

PMID- 18619421
TI  - Inactivating potassium currents in apical and basal turn inner hair cells from
      guinea-pig cochlea.
AB  - Tetraethylammonium (TEA)-sensitive potassium currents in the cochlear inner hair
      cells (IHCs) possess the kinetics of fast inactivation. IHCs of guinea-pigs were
      separately isolated from the apical and basal turns and the tonotopic gradient of
      inactivation kinetics was investigated. TEA-sensitive potassium currents showed
      voltage-dependent time constant of the inactivation phase both in apical and
      basal IHCs, however, the degree of inactivation (compared to the ratio between
      the steady-state current and initial peak current) was voltage-independent.
      Inactivation time constant was faster in basal IHCs than in apical IHCs and the
      degree of inactivation was greater in basal IHCs than in apical IHCs, suggesting
      that inactivation was more predominant in basal IHCs than in apical IHCs.

PMID- 18619422
TI  - CRH mRNA expression in the hypothalamic paraventricular nucleus is inhibited
      despite the activation of the hypothalamo-pituitary-adrenal axis during
      starvation.
AB  - Corticotropin-releasing hormone (CRH) is one of the anorexigenic neuropeptides,
      and indeed the expression of hypothalamic CRH is known to be inhibited by
      starvation. To clarify whether elevated plasma glucocorticoid during starvation
      is responsible for the CRH suppression, we examined the expression level of
      hypothalamic CRH mRNA after food deprivation in adrenalectomized, plasma
      corticosterone (B)-clamped animals. Male Wistar rats were divided into 2 groups:
      one group had adrenalectomy (ADX) and B pellet implantation (ADX+B, n=42), and
      the other group had only sham operation (sham, n=42). Rats were then treated with
      either ad libitum food supply or food deprivation for up to 96 h. The expression
      of CRH mRNA in the paraventricular nucleus (PVN) was estimated by in situ
      hybridization. After food deprivation, mean plasma B level was markedly elevated
      in sham group, but almost clamped in the ADX+B group. In this experimental
      condition, CRH mRNA in the PVN was significantly decreased in the sham group,
      whereas no change was obtained in the ADX+B group. Our data suggest the decrease
      in CRH mRNA seems to be related to the elevated glucocorticoid level during
      starvation. The status of hyperadrenocorticism without activation of CRH led us
      to speculate that adrenocortical function is predominant in the hypothalamic
      pituitary-adrenal (HPA) axis during starvation.

PMID- 18619423
TI  - Cortical modulation by nucleus basalis magnocellularis corticopetal cholinergic
      neurons during anxiety-like states is reflected by decreases in delta.
AB  - Previous research has demonstrated that nucleus basalis magnocellularis (nbm)
      corticopetal cholinergic neurons modulate anxiety-like states, but cortical
      modulation by these neurons during anxiety-like states has not been
      characterized. In order to address this, we documented the effect of nbm
      corticopetal cholinergic lesions on cortical activity in direct (prefrontal
      cortex) and indirect (retrosplenial cortex) targets of nbm corticopetal
      cholinergic neurons during footshock induced operant suppression. The gamma/delta
      ratio and theta were used as indices of cortical activity, because these
      components of the electroencephalogram (EEG) are sensitive to basal forebrain
      corticopetal cholinergic modulation. During operant suppression, increases in the
      gamma/delta ratio and augmented theta were observed in both cortical EEGs.
      Lesions attenuated operant suppression and the gamma/delta ratio, but had no
      effect on increased theta. The effect of nbm corticopetal cholinergic lesions on
      the gamma/delta ratio was driven by the effect of the lesions on the delta band.
      The results of the study demonstrate that during anxiety-like states 1) decreases
      in delta reflect the action of nbm corticopetal cholinergic neurons, 2) nbm
      corticopetal cholinergic neurons alter neural processes in direct and indirect
      cortical targets, and 3) cortical theta is not dependent on the integrity of nbm
      corticopetal cholinergic neurons.

PMID- 18619424
TI  - Behavioral and temperature effects of delta 9-tetrahydrocannabinol in human
      relevant doses in rats.
AB  - Marijuana smoking dramatically alters responses to various environmental stimuli.
      To study this phenomenon, we assessed how delta-9-tetrahydrocannabinol (THC), a
      primary psychoactive ingredient of marijuana, affects locomotor and brain
      (nucleus accumbens or NAcc), muscle and skin temperature responses to natural
      arousing stimuli (one-minute tail-pinch and one-minute social interaction with
      another male rat) and iv cocaine (1 mg/kg) in male rats. THC was administered at
      three widely varying doses (0.5, 2.0 and 8.0 mg/kg, ip), and the drug-induced
      changes in basal values and responses to stimuli were compared to those occurring
      following ip vehicle injections (control). Each stimulus in control conditions
      caused acute locomotor activation, a prolonged increase in brain and muscle
      temperature (0.6-1.0 degrees C for 20-50 min) and transient decrease in skin
      temperature (-0.6 degrees C for 1-3 min). While THC at any dose had a tendency to
      decrease spontaneous locomotion as well as brain and muscle temperatures, true
      hypothermia and hypoactivity as well as clearly diminished locomotor and
      temperature responses to all stimuli were only seen following the largest dose.
      In this case, temperature decreases in the NAcc were stronger than in the muscle,
      suggesting metabolic brain inhibition as the primary cause of hypoactivity,
      hypothermia and hyporesponsiveness. While weaker in strength and without
      associated vasodilatation, this response pattern is mimicked by general
      anesthetics, questioning to what extent the hypothermic action of THC is specific
      (i.e., mediated via endogenous cannabinoid receptors) or non-specific, reflecting
      drug interaction with membrane lipids or other receptors. In contrast, weaker
      behavioral and temperature effects of THC at lower doses resemble those of
      diazepam, whose locomotion- and temperature-decreasing effects are evident only
      in activated conditions, when rats are moving and basal temperatures are
      elevated.

PMID- 18619425
TI  - The nicotinic alpha7 acetylcholine receptor agonist ssr180711 is unable to
      activate limbic neurons in mice overexpressing human amyloid-beta1-42.
AB  - Recent studies have demonstrated that amyloid-beta1-42 (Abeta1-42) binds to the
      nicotinergic alpha7 acetylcholine receptor (alpha7 nAChR) and that the
      application of Abeta1-42 to cells inhibits the function of the alpha7 nAChR. The
      in vivo consequences of the pharmacological activation of the alpha7 nAChR have
      not been examined. The aim of this study has been to evaluate the efficacy of
      alpha7 nAChR modulators in transgene mice that overexpress human amyloid
      precursor protein and accumulate Abeta1-40 and Abeta1-42. In accordance with
      observations in human Alzheimer tissues, we show here through the use of co
      immunoprecipitation that human Abeta-immunoreactive peptides bind to mice alpha7
      nAChR in vivo. Agonists of the alpha7 nAChR improve memory and attentional
      properties and increase immediate early gene expression in the prefrontal cortex
      and the nucleus accumbens. We show that acute systemic administration of the
      alpha7 nAChR agonist SSR180711 (10 mg/kg) result in a significant increase in Fos
      protein levels in the shell of nucleus accumbens in wild-type mice, but has no
      effect in the transgene mice. There were fewer cell bodies expressing Fos in the
      prefrontal cortex of transgene mice, and in this region no induction was achieved
      after administration with SSR180711 in either of the two groups. These results
      suggest that overexpression of human Abeta peptides perhaps via direct
      interaction with alpha7 nAChR, inhibit alpha7 nAChR-dependent neurotransmission
      in vivo and emphasize that clinical trials testing alpha7 nAChR agonists should
      be related to the content of Abeta peptides in the patient's nervous system.

PMID- 18619426
TI  - Perspective taking is associated with specific facial responses during empathy
      for pain.
AB  - Witnessing the distress of others can result both in empathy and personal
      distress. Perspective-taking has been assigned a major role in the elicitation
      and modulation of these vicarious responses. However, little is known about how
      perspective-taking affects the psychophysiological correlates of empathy vs.
      personal distress. We recorded facial electromyographic and electrocardiographic
      activity while participants watched videos of patients undergoing painful sonar
      treatment. These videos were watched using two distinct perspectives: a)
      imagining the patient's feelings ('imagine other'), or b) imagining to be in the
      patient's place ('imagine self'). The results revealed an unspecific frowning
      response as well as activity over the M. orbicularis oculi region which was
      specific to the 'imagine self' perspective. This indicates that the pain-related
      tightening of the patients orbits was matched by participants when adopting this
      perspective. Our findings provide a physiological explanation for the more direct
      personal involvement and higher levels of personal distress associated with
      putting oneself explicitly into someone elses shoes. They provide further
      evidence that empathy does not only rely on automatic processes, but is also
      strongly influenced by top-down control and cognitive processes.

PMID- 18619427
TI  - Long-term cigarette smoke exposure increases uncoupling protein expression but
      reduces energy intake.
AB  - The appetite suppressing effect of tobacco is a major driver of smoking
      behaviour; however few studies have addressed the effects of chronic cigarette
      smoke exposure (SE) on appetite, body weight and metabolic markers. We compared
      the effects of SE to equivalent food restriction (pair-fed, PF), against sham
      exposure, on body weight, adiposity, cytokines, and levels of uncoupling proteins
      (UCP) and brain neuropeptide Y (NPY) in male Balb/C mice. SE rapidly induced
      anorexia, and after 12 weeks, SE and PF groups were lighter than control animals
      (23.9+/-0.2, 25.5+/-0.5, 26.8+/-0.4 g respectively, P<0.05). White fat (WAT)
      masses were reduced by both SE and PF. Plasma leptin and insulin were reduced in
      SE mice; insulin was further reduced by PF. Brown fat UCP1 and 3 mRNA were
      increased in SE animals relative to PF animals, possibly promoting thermogenesis.
      WAT mRNA expression of the inflammatory cytokine, TNFalpha was doubled by SE,
      while IL-6 was reduced by both PF and SE. Hypothalamic NPY content was increased
      by SE (89.3+/-2.8 vs. 75.9+/-2.4 ng control, P<0.05), and more by PF (100.7+/-3.4
      ng, P<0.05 compared to both groups), suggesting disinhibition due to reduced
      adipose derived leptin. In contrast to equivalent food restriction, cigarette
      smoke exposure reduced body weight and total hypothalamic NPY, and increased
      thermogenesis and markers of inflammation. The suppressed hypothalamic NPY and
      increased UCPs may contribute to the spontaneous hypophagia and extra weight loss
      in SE animals. These findings contribute to our understanding of weight loss in
      smoking-related lung disease, suggesting a greater impact than that due to
      anorexia alone.

PMID- 18619428
TI  - Lamellar rearrangement of internal lipids from human hair.
AB  - The internal lipids were extracted from untreated hair without surface lipids.
      Liposomes were formed with the internal lipids at different hydration levels to
      determine the organization of these lipids and the influence of the water content
      on the lamellar structure of the hair fibres by X-ray Scattering (SAXS). Two
      structures of hair lipids were observed at 4.5 and approximately 9.0 nm with a
      different behaviour as a function of water content: the largest bilayer being the
      one that showed a capacity to retain water inside its structure. SAXS was also
      applied directly to three samples: a packed swatch of hair fibres at 60% RH,
      fibres soaked in water and delipidized fibres. Only the lamella at 9.0 nm was
      slightly affected by water content. Moreover, there was a small diminution in
      intensity probably due to a high permeability of wet fibres which could give rise
      to a disorder of the lipid structure. These two lamellar rearrangements are
      probably made up of lipids with a different and specific hydrophilic/hydrophobic
      balance.

PMID- 18619429
TI  - Type 2 diabetes significantly modulates the cardiovascular risk conferred by the
      PAI-1 -675 4G/5G polymorphism in angiographied coronary patients.
AB  - BACKGROUND: The association of the -675 4G/5G polymorphism of the plasminogen
      activator inhibitor-1 (PAI-1) gene with cardiovascular disease in patients with
      type 2 diabetes (T2DM) is unknown. METHODS: Genotyping was performed in 672
      consecutive Caucasian patients undergoing coronary angiography for the evaluation
      of stable coronary artery disease (CAD). Vascular events were recorded over 4
      years. RESULTS: In non-diabetic subjects (n=524), the homozygous PAI-1 4G4G
      genotype was significantly associated with significant coronary stenoses>or=50%
      (adjusted odds ratio (OR) OR=1.84 [1.17-2.92]; p=0.009); however, in T2DM
      patients (n=148) no such association was observed (OR=0.67 [0.26-1.71]; p=0.401).
      An interaction term T2DMx4G4G genotype was significant (p=0.006), indicating a
      significantly stronger association of the polymorphism with CAD in non-diabetic
      subjects than in patients with T2DM. Also prospectively, the 4G4G genotype
      conferred an increased risk of vascular events in non-diabetic subjects but not
      in T2DM patients (hazard ratios 1.76 [1.13-2.74]; p=0.014 and 0.68 [0.30-1.54];
      p=0.360, respectively). Again, the interaction T2DMx4G4G genotype was significant
      (p=0.018). CONCLUSIONS: Presence of T2DM significantly modulates the vascular
      risk conferred by the PAI-1 -675 4G/5G polymorphism in angiographied coronary
      patients.

PMID- 18619430
TI  - A hydrophilic-interaction chromatography tandem mass spectrometry method for
      quantitation of serum s-adenosylmethionine in patients infected with human
      immunodeficiency virus.
AB  - BACKGROUND: s-Adenosylmethionine (SAM)1 has been suggested as a diagnostic test
      and surrogate marker for Pneumocystis jirovecii pneumonia (PCP) in HIV-positive
      patients. In this study, we report a robust hydrophilic-interaction liquid
      chromatography tandem mass spectrometry (LC-MS/MS) assay that can be used to
      quantitate serum SAM in clinical laboratories. METHODS: Proteins in serum samples
      were precipitated using trichloroacetic acid. The supernatant was separated after
      centrifugation. D3d3-SAM was added as the internal standard. SAM and d3-SAM were
      extracted using a mixed-mode cation exchange column. Extracts were dried under
      nitrogen and reconstituted in H2O and acetonitrile (1:9, vol:vol). HPLC-tandem
      mass spectrometry analysis was performed with a silica column and multiple
      reaction monitoring for SAM and d3-SAM. RESULTS: The limit of quantitation (LOQ)
      for SAM was 10 ng/mL. The assay was linear between 10 and 500 ng/mL. Intra-assay
      coefficient of variation (CV) was 8% and inter-assay CV was 17% at the LOQ.
      Turnaround time for each specimen was approximately 1 h. Using this method, we
      found that serum SAM concentration was correlated with fasting status, especially
      methionine intake. We also measured acute and convalescent serum SAM levels of 8
      HIV-positive patients with PCP and non-PCP pneumonia. SAM concentrations in
      convalescent samples were significantly increased compared to acute levels only
      in patients with PCP. CONCLUSIONS: The LC-MS/MS method had sufficient analytical
      sensitivity for detecting low levels of SAM found in HIV-infected patients and
      can be used for quantitative measurements in a clinical laboratory. This method
      facilitates research and possible clinical application of SAM as a marker for
      PCP.

PMID- 18619431
TI  - Induction of cell cycle arrest and apoptosis by 5-fluorouracil in laryngeal
      cancer cells containing HPV16 E6 and E7 oncoproteins.
AB  - OBJECTIVE: To investigate the cytotoxic effect of 5-fluorouracil (5Fu) on HPV16
      associated laryngeal cancer cells. DESIGN AND METHODS: Cytotoxicity assay and
      TUNEL assay were used to assess the effect of 5Fu on laryngeal cancer cells
      transfected with HPV16 E6 or E7. RESULTS: 5Fu induced apoptosis in the cells
      either with or without HPV16 in a dose- and time-dependent manner. 5Fu caused the
      accumulation of active pRb and p21(WAF1/CIP1), together with an increase in Bak
      and Bax expression and a decrease in Bcl-2 levels in all the transfected cells.
      G(1)/S phase cell cycle arrest was associated with the antiproliferation activity
      of 5Fu. 5Fu also presented some effects on the E6 and E7 oncoproteins.
      CONCLUSIONS: HPV16 E6 and E7 oncoproteins do not prevent 5Fu-medicated apoptosis
      and G(1)/S cell arrest in laryngeal cancers. The sensitivity of 5Fu treatment is
      associated with the decrease of Bcl-2 and/or the increase in Bak and
      p21(WAFI/CIP1).

PMID- 18619432
TI  - Specific, rapid, and sensitive enzymatic measurement of sphingomyelin,
      phosphatidylcholine and lysophosphatidylcholine in serum and lipid extracts.
AB  - OBJECTIVE: Human serum sphingomyelin (SM) and phosphatidylcholine (PC) play
      important roles in the development of atherosclerosis. However, there are no
      rapid and sensitive methods for SM and PC measurement. The present report
      describes a novel enzymatic method for measuring SM, PC and
      lysophosphatidylcholine (lyso-PC) levels in plasma and lipid extracts. DESIGN AND
      METHODS: The total choline-containing phospholipids (total PL), SM and PC were
      measured using a two-reagent system involving specific enzymes for choline-based
      phospholipids. The procedure was performed using either microplate or automatic
      analyzer technology. The concentration of lyso-PC was calculated by subtracting
      the concentration of SM plus PC from the total PL concentration. RESULTS: Assay
      results showed linear correlations between sample concentration and absorbance.
      The within-run and between-run coefficients of variation for PC, SM, and lyso-PC
      concentrations were 2.0-4.4% for the microplate analyzer and 0.9-2.9% for the
      automatic analyzer. Analysis of normal human serum showed that the total PL
      concentration strongly correlated with the SM plus PC concentration (r=0.9850).
      There were moderate correlations between serum PC and SM levels (r=0.6228) and
      between serum PC and lyso-PC levels (r=0.7806). SM, PC, and lyso-PC levels in
      normal human serum (n=50) were 0.54+/-0.07, 1.99+/-0.22 and 0.60+/-0.15 mmol/L,
      respectively. CONCLUSION: The present enzymatic method allowed for rapid, simple,
      and accurate measurement of SM, PC, and lyso-PC levels in lipid extracts and in
      serum. The method is suitable for both microplate and automatic analyzer assays.

PMID- 18619433
TI  - Inflammatory sites as a source of plasma neopterin: measurement of high levels of
      neopterin and markers of oxidative stress in pus drained from human abscesses.
AB  - OBJECTIVES: Plasma neopterin is a clinical marker of inflammation. Interferon
      gamma triggers 7,8-dihydroneopterin and its oxidation product, neopterin, to be
      released from macrophages. 7,8-dihydroneopterin is a potent antioxidant which can
      protect macrophages from oxidative damage in vitro. This study examined whether
      7,8-dihydroneopterin/neopterin levels reach sufficient concentrations in human
      pus to provide antioxidant activity and be the source of plasma neopterin. DESIGN
      AND METHODS: Pus was removed by needle aspiration from 19 patients and examined
      for total neopterin, protein-bound DOPA, dityrosine, alpha-tocopherol, lipid
      oxidation and protein carbonyls. RESULTS: Total neopterin was detected between 50
      nM and 1.2 microM, with an average concentration of 0.51 microM. Significant
      quantities of oxidized proteins and lipids were detected. alpha-Tocopherol
      concentrations positively correlate with total neopterin levels. CONCLUSIONS:
      Total neopterin levels found in the pus was up to 100 times higher than that
      reported in plasma, suggesting plasma neopterin originates from inflammatory
      sites. The concentration of total neopterin suggests that 7,8-dihydroneopterin
      could act as an antioxidant during inflammation.

PMID- 18619434
TI  - Natural genetic variation in acclimation capacity at sub-zero temperatures after
      cold acclimation at 4 degrees C in different Arabidopsis thaliana accessions.
AB  - Freezing tolerance is an important factor in the geographical distribution of
      plants and strongly influences crop yield. Many plants increase their freezing
      tolerance during exposure to low, nonfreezing temperatures (cold acclimation) and
      acclimation may continue at mild freezing temperatures in a process termed sub
      zero acclimation. There is considerable natural variation in the cold acclimation
      capacity of Arabidopsis that has been used to study the molecular basis of this
      trait, but much less is known about the molecular basis of sub-zero acclimation.
      Freezing tolerance of detached leaves from the accessions C24, Columbia-0,
      Rschew, and Tenela was investigated using an electrolyte leakage assay. Sub-zero
      acclimation could be achieved by shifting plants from 4 degrees C to -3 degrees
      C, or by using detached leaves, either in the presence or absence of ice
      nucleation. The magnitude of the increase in freezing tolerance depended on both
      temperature and duration of sub-zero acclimation and while Columbia-0 showed no
      significant increase in freezing tolerance, the other three accessions increased
      their freezing tolerance significantly. The levels of several sugars that have
      been shown to be induced during cold acclimation at nonfreezing temperatures were
      not strongly changed during sub-zero acclimation and there was no correlation
      between the increases in freezing tolerance and sugar levels in the different
      accessions. Expression of the three cold induced CBF transcription factor genes
      and five of their representative target COR genes was moderately increased during
      sub-zero acclimation, but again there was no correlation to changes in freezing
      tolerance, indicating that the genetic and molecular basis of sub-zero
      acclimation is most likely different from that of cold acclimation at above
      freezing temperatures. Further studies will be needed to reveal novel signal
      transduction pathways and protective mechanisms important in sub-zero
      acclimation.

PMID- 18619435
TI  - Quantification and variation in experimental studies of morphogenesis.
AB  - The application of quantitative methods has long been the norm in comparative and
      evolutionary studies of morphology, but within the field of experimental
      embryology mathematical descriptions of anatomical form are seldom calculated,
      and morphological variation within treatment groups is rarely taken into account.
      Here we argue that many of the analytical techniques that are commonly applied in
      other areas of morphological research are also well suited for experimental
      studies of anatomical development. The application of these methodologies shows
      promise for augmenting such endeavors by enhancing researchers' ability to detect
      morphological patterns, account for developmental variation, and employ
      statistical methods. We review selected studies of experimental morphogenesis
      that underscore the potential of quantitative methods to reveal important aspects
      of anatomical development and growth. These examples demonstrate the benefits of
      quantifying ontogenetic data and accounting for developmental variation, and we
      suggest that the adoption of such practices by researchers performing
      experimental studies of morphogenesis will enhance our understanding of the
      processes by which genetic changes affect anatomical formation.

PMID- 18619436
TI  - Grhl3 and Lmo4 play coordinate roles in epidermal migration.
AB  - In addition to its role in formation of the epidermal barrier, the mammalian
      transcription factor Grainy head-like 3 (Grhl3) is also essential for neural tube
      closure and wound repair, processes that are dependent in part on epidermal
      migration. Here, we demonstrate that the LIM-only domain protein, LMO4 serves as
      a functional partner of GRHL3 in its established roles, and define a new
      cooperative role for these factors in another developmental epidermal migration
      event, eyelid fusion. GRHL3 and LMO4 interact biochemically and genetically, with
      mutant mice exhibiting fully penetrant exencephaly, thoraco-lumbo-sacral spina
      bifida, defective skin barrier formation, and a co-incident eyes-open-at-birth
      (EOB) phenotype, which is not observed in the original individual null lines. The
      two genes are co-expressed in the surface ectoderm of the migrating eyelid root,
      and electron microscopy of Grhl3/Lmo4-null eyes reveals a failure in epithelial
      extension and a lack of peridermal clump formation at the eyelid margins.
      Accumulation of actin fibers is also absent in the circumference of these
      eyelids, and ERK1/2 phosphorylation is lost in the epidermis and eyelids of
      Grhl3(-/-)/Lmo4(-/-) embryos. Keratinocytes from mutant mice fail to "heal" in in
      vitro scratch assays, consistent with a general epidermal migratory defect that
      is dependent on ERK activation and actin cable formation.

PMID- 18619437
TI  - MUC1 and estrogen receptor alpha gene polymorphisms in dry eye patients.
AB  - Dry eye syndrome is a collection of common disorders of multifactorial etiology.
      Although the epidemiology of dry eye has been well studied, reports of genetic
      patterns that might influence susceptibility to dry eye are few. We reported that
      the frequency of non-Sjogren's aqueous-deficient dry eye patients expressing only
      the MUC1/A splice variant of the mucin MUC1 may be lower than that of a normal
      control group [Imbert, Y., Darling, D.S., Jumblatt, M.M., Foulks, G.N., Couzin,
      E.G., Steele, P.S., Young, W.W., Jr., 2006. MUC1 splice variants in human ocular
      surface tissues: possible differences between dry eye patients and normal
      controls. Exp. Eye Res. 83, 493-501]. Also, He et al. [He, Y., Li, X., Bao, Y.,
      Sun, J., Liu, J., 2006. The correlation of polymorphism of estrogen receptor gene
      to dry eye syndrome in postmenopausal women. Yan. Ke. Xue. Bao. 22, 233-236]
      reported a difference between Chinese dry eye and control groups in the frequency
      of a polymorphism in estrogen receptor alpha (ERalpha). In the present study we
      determined the statistical significance and generality of these observations and
      tested if the MUC1 splice variant difference between subject groups reflected a
      difference in the MUC1 variable number of tandem repeat (VNTR) size class. There
      was a perfect correlation between the MUC1/A or MUC1/B splice variant pattern and
      the SNP genotype frequency of the SNP (rs4072037) controlling that splicing
      event. In contrast, western and Southern blotting indicated that MUC1 VNTR size
      class corresponded to the MUC1 SNP genotype in only 80% of cases. We determined
      the status of the MUC1 SNP in normal and dry eye populations all of whom were
      female Caucasians. The MUC1 SNP genotype frequency of the normal control group
      was statistically different from both the non-Sjogren's aqueous-deficient dry eye
      group with ocular surface staining (P=0.017) and the evaporative dry eye group
      (P=0.015). We also tested SNP rs2234693 to analyze the polymorphism in the
      ERalpha gene and found no significant difference in the SNP genotype frequency
      between the control group and either of the dry eye subtypes. Thus, among
      Caucasians there is no evidence for an association of the ERalpha gene
      polymorphism with dry eye syndrome as previously described in a Chinese
      population. In conclusion, the etiologies of evaporative dry eye and non
      Sjogren's aqueous-deficient dry eye are known to be different. However, our
      results suggest that both of these subtypes of dry eye disease may share a common
      mechanism or factor related to MUC1 genotypic differences that affects
      susceptibility to ocular surface damage. This altered susceptibility may not be
      related to the MUC1 VNTR size class. Therefore, mechanisms influencing protection
      of the ocular surface against inflammation and damage in different types of dry
      eye disease warrant further investigation particularly in relation to MUC1
      genotype.

PMID- 18619438
TI  - Phosphorylation and compactness of neurofilaments in multiple sclerosis:
      indicators of axonal pathology.
AB  - AIMS: Axonal pathology extends to the axonal cytoarchitecture leaving its
      signature on axoskeletal proteins. This study investigated whether neurofilament
      (NfH) phosphorylation would relate to the dynamics of axonal pathology in
      multiple sclerosis (MS). METHODS: NfH phosphoforms (SMI32, SMI34, SMI35) were
      quantified by ELISA from microdissected samples of control and MS brain and
      spinal cord. Individual axons were analysed by electron microscopy,
      densitometrically and morphologically in adjacent tissue sections. Experiments
      were carried out pre- and post enzymatic dephosphorylation. RESULTS: In control
      tissue a rostro-caudal gradient of NfH indicated an increase in axonal density
      from the brain gray matter towards the spinal cord. The highest levels of
      phosphorylated and hyperphosphorylated NfH were found in acute lesions of brain
      and spinal cord, in contrast to chronic lesions where levels were lower than in
      white matter, consistent with axonal loss. Dephosphorylated NfH was higher, but
      less densly packed in MS white matter axons compared to control tissue.
      CONCLUSIONS: The findings suggest that a less organised/compact axoskeleton or
      impaired axonal transport may represent an early sign of axonal pathology within
      the normal appearing white matter in MS. Subsequently a proportional increase of
      dephosphorylated NfH, aberrant phosphorylation and/or aggregation may occur
      whilst the protein is transported through the white matter towards the MS plaque,
      where hyperphosphorylated NfH dominates.

PMID- 18619439
TI  - Plasmodium falciparum: enhanced soluble expression, purification and biochemical
      characterization of lactate dehydrogenase.
AB  - Plasmodium lactate dehydrogenase (pLDH), owing to unique structural and kinetic
      properties, is a well known target for antimalarial compounds. To explore a new
      approach for high level soluble expression of Plasmodium falciparum lactate
      dehydrogenase (PfLDH) in E. coli, PfLDH encoding sequence was cloned into pQE-30
      Xa vector. When transformed E. coli SG13009 cells were induced at 37 degrees C
      with 0.5mM isopropyl beta-d-thiogalactoside (IPTG) concentration, the protein was
      found to be exclusively associated with inclusion bodies. By reducing cell growth
      temperature to 15 degrees C and IPTG concentration to 0.25 mM, it was possible to
      get approximately 82% of expressed protein in soluble form. Recombinant PfLDH
      (rPfLDH) was purified to homogeneity yielding 18 mg of protein/litre culture.
      rPfLDH was found to be biologically active with specific activity of 453.8
      micromol/min/mg. The enzyme exhibited characteristic reduced substrate inhibition
      and enhanced k(cat) [(3.2+/-0.02)x10(4)] with 3-acetylpyridine adenine
      dinucleotide (APAD+). The procedure described in this study may provide a
      reliable and simple method for production of large quantities of soluble and
      biologically active PfLDH.

PMID- 18619440
TI  - Serum starvation induces H2AX phosphorylation to regulate apoptosis via p38 MAPK
      pathway.
AB  - Phosphorylation of H2AX is believed to be associated with the repair of damaged
      DNA. Recent findings suggest a novel function of H2AX in cellular apoptosis.
      Specifically, it was shown that ultraviolet A-activated JNK phosphorylates H2AX
      to regulate apoptosis. Here we show that serum starvation induces H2AX
      phosphorylation and apoptosis independent of the JNK pathway. Serum starvation
      induced p38 phosphorylation, whereas it did not affect the phosphorylation of ERK
      or JNK. Inhibition of p38 reduced H2AX phosphorylation and apoptosis.
      Furthermore, p38 was found to phosphorylate H2AX directly in vitro and was
      colocalized with H2AX in vivo. Finally, we demonstrate that H2AX phosphorylation
      is required for serum starvation-induced apoptosis. Taken together, these data
      elucidate a novel signaling pathway (p38/H2AX) to regulate apoptosis.

PMID- 18619441
TI  - Dependence of trans-ADP-ribosylation and nuclear glycolysis on the Arg 34-ATP
      complex of Zn2+ finger I of poly-ADP-ribose polymerase-1.
AB  - The H-bonded complex of ATP with Arg 34 of Zn2+ finger I of poly-ADP-ribose
      polymerase-1 (PARP-1) determines trans-oligo-ADP-ribosylation from NAD+ to
      proteins other than PARP-1. This mechanism was tested in lysolecithin fractions
      of non-malignant and cancer cells separately and after their recombination.
      Cellular PARP-1 activity was recovered when the centrifugal sediment was
      recombined with the supernatant fraction containing cellular ADP-ribose oligomer
      acceptor proteins. Combination of the matrix fraction (Mx) of cancer cells
      (lacking OXPHOS) with its supernatant had the same PARP-1 activity as the Mx
      alone. The supernatant of non-malignant cells was replaced by glycolytic enzymes
      as ADP-ribose acceptor. The hexokinase activity of the supernatant increased when
      OXPHOS of intact cells was uncoupled by carbonyl cyanide 4-(trifluoro methoxy)
      phenylhydrazone. trans-ADP-ribosylation was demonstrated by polyacrylamide gel
      electrophoresis.

PMID- 18619442
TI  - Dehydroascorbate and glucose are taken up into Arabidopsis thaliana cell cultures
      by two distinct mechanisms.
AB  - The possible involvement of glucose (Glc) carriers in the uptake of vitamin C in
      plant cells is still a matter of debate. For the first time, it was shown here
      that plant cells exclusively take up the oxidised dehydroascorbate (DHA) form.
      DHA uptake is not affected by 6-bromo-6-deoxy-ascorbate, an ascorbate (ASC)
      analogue, specifically demonstrating ASC uptake in animal cells. There is no
      competition between Glc and DHA uptake. Moreover, DHA and Glc carriers respond in
      the opposite manner to different inhibitors (cytochalasin B, phloretin and
      genistein). In conclusion, the plant plasma membrane DHA carrier is distinct from
      the plant Glc transporters.

PMID- 18619443
TI  - Electronic clinical challenges and images in GI. Colonic tuberculosis.

PMID- 18619444
TI  - Screening and surveillance for the early detection of colorectal cancer and
      adenomatous polyps.

PMID- 18619445
TI  - Intrahepatic murine CD8 T-cell activation associates with a distinct phenotype
      leading to Bim-dependent death.
AB  - BACKGROUND & AIMS: Chronic infections by hepatotropic viruses such as hepatitis B
      and C are generally associated with an impaired CD8 T-cell immune response that
      is unable to clear the virus. The liver is increasingly recognized as an
      alternative site in which primary activation of CD8 T cells takes place, a
      property that might explain its role in inducing tolerance. However, the
      molecular mechanism by which intrahepatically activated T cells become tolerant
      is unknown. Here, we investigated the phenotype and fate of naive CD8 T cells
      activated by hepatocytes in vivo. METHODS: Transgenic mouse models in which the
      antigen is expressed in lymph nodes and/or in the liver were adoptively
      transferred with naive CD8 T cells specific for the hepatic antigen. RESULTS:
      Liver-activated CD8 T cells displayed poor effector functions and a unique
      CD25(low) CD54(low) phenotype. This phenotype was associated with increased
      expression of the proapoptotic protein Bim and caspase-3, demonstrating that
      these cells are programmed to die following intrahepatic activation. Importantly,
      we show that T cells deficient for Bim survived following intrahepatic
      activation. CONCLUSIONS: This study identifies Bim for the first time as a
      critical initiator of T-cell death in the liver. Thus, strategies inhibiting the
      up-regulation of this molecule could potentially be used to rescue CD8 T cells,
      clear the virus, and reverse the outcome of viral chronic infections affecting
      the liver.

PMID- 18619446
TI  - Defining disease with laser precision: laser capture microdissection in
      gastroenterology.
AB  - Laser capture microdissection (LCM) is an efficient and precise method for
      obtaining pure cell populations or specific cells of interest from a given tissue
      sample. LCM has been applied to animal and human gastroenterology research in
      analyzing the protein, DNA, and RNA from all organs of the gastrointestinal
      system. There are numerous potential applications for this technology in
      gastroenterology research, including malignancies of the esophagus, stomach,
      colon, biliary tract, and liver. This technology can also be used to study
      gastrointestinal infections, inflammatory bowel disease, pancreatitis, motility,
      malabsorption, and radiation enteropathy. LCM has multiple advantages when
      compared with conventional methods of microdissection, and this technology can be
      exploited to identify precursors to disease, diagnostic biomarkers, and
      therapeutic interventions.

PMID- 18619447
TI  - Biomarkers and photodynamic therapy for Barrett's esophagus: time to FISH or cut
      bait?

PMID- 18619450
TI  - Cigarette smoking and colorectal cancer risk: a burning issue.

PMID- 18619451
TI  - Statins are safe for the treatment of hypercholesterolemia in patients with
      chronic liver disease.

PMID- 18619452
TI  - Clinical challenges and images in GI. Syphilitic sigmoiditis complicated by
      membranous nephropathy.

PMID- 18619455
TI  - A new twist in the cholesterol metabolism-based enterohepatic connection.

PMID- 18619453
TI  - Clinical challenges and images in GI. Colonic pseudo-obstruction as a rare
      complication of herpes zoster.

PMID- 18619456
TI  - Clinical challenges and images in GI. Duodenal gangliocytic paraganglioma.

PMID- 18619457
TI  - Three sequencing companies join the 1000 genomes project.

PMID- 18619459
TI  - Folate and vitamin B6 intake and risk of colon cancer in relation to p53
      expression.
AB  - BACKGROUND & AIMS: Considerable evidence suggests that a low-folate diet
      increases the risk of colorectal cancer, although the results of a recent
      randomized trial indicate that folate supplementation may not reduce the risk of
      adenoma recurrence. In laboratory models, folate deficiency appears to induce p53
      mutation. METHODS: We immunohistochemically assayed p53 expression in paraffin
      fixed colon cancer specimens in a large prospective cohort of women with 22 years
      of follow-up to examine the relationship of folate intake and intake of other one
      carbon nutrients to risks by tumor p53 expression. RESULTS: A total of 399
      incident colon cancers accessible for p53 expression were available. The effect
      of folate differed significantly according to p53 expression (P(heterogeneity) =
      .01). Compared with women reporting folate intake <200 microg/day, the
      multivariate relative risks (RRs) for p53-overexpressing (mutated) cancers were
      0.54 (95% confidence interval [CI], 0.36-0.81) for women who consumed 200-299
      microg/day, 0.42 (95% CI, 0.24-0.76) for women who consumed 300-399 microg/day,
      and 0.54 (95% CI, 0.35-0.83) for women who consumed >or=400 microg/day. In
      contrast, total folate intake had no influence on wild-type tumors (RR, 1.05; 95%
      CI, 0.73-1.51; comparing >or=400 with <200 microg/day). Similarly, high vitamin
      B(6) intake conferred a protective effect on p53-overexpressing cancers (top
      versus bottom quintile: RR, 0.57; 95% CI, 0.35-0.94; P(heterogeneity) = .01) but
      had no effect on p53 wild-type tumors. CONCLUSIONS: We found that low folate and
      vitamin B(6) intake was associated with an increased risk of p53-overexpressing
      colon cancers but not wild-type tumors.

PMID- 18619460
TI  - Immune response against frameshift-induced neopeptides in HNPCC patients and
      healthy HNPCC mutation carriers.

PMID- 18619461
TI  - Kinetic traps in the folding of beta alpha-repeat proteins: CheY initially
      misfolds before accessing the native conformation.
AB  - The beta alpha-repeat class of proteins, represented by the (beta alpha)(8)
      barrel and the alpha/beta/alpha sandwich, are among the most common structural
      platforms in biology. Previous studies on the folding mechanisms of these motifs
      have revealed or suggested that the initial event involves the submillisecond
      formation of a kinetically trapped species that must at least partially unfold
      before productive folding to the respective native conformation can occur. To
      test the generality of these observations, CheY, a bacterial response regulator,
      was subjected to an extensive analysis of its folding reactions. Although earlier
      studies had proposed the formation of an off-pathway intermediate, the data
      available were not sufficient to rule out an alternative on-pathway mechanism. A
      global analysis of single- and double-jump kinetic data, combined with
      equilibrium unfolding data, was used to show that CheY folds and unfolds through
      two parallel channels defined by the state of isomerization of a prolyl peptide
      bond in the active site. Each channel involves a stable, highly structured
      folding intermediate whose kinetic properties are better described as the
      properties of an off-pathway species. Both intermediates subsequently flow
      through the unfolded state ensemble and adopt the native cis-prolyl isomer prior
      to forming the native state. Initial collapse to off-pathway folding
      intermediates is a common feature of the folding mechanisms of beta alpha-repeat
      proteins, perhaps reflecting the favored partitioning to locally determined
      substructures that cannot directly access the native conformation. Productive
      folding requires the dissipation of these prematurely folded substructures as a
      prelude to forming the larger-scale transition state that leads to the native
      conformation. Results from Go-modeling studies in the accompanying paper
      elaborate on the topological frustration in the folding free-energy landscape of
      CheY.

PMID- 18619462
TI  - Conformational plasticity of the Gerstmann-Straussler-Scheinker disease peptide
      as indicated by its multiple aggregation pathways.
AB  - The existence of several prion strains and their capacity of overcoming species
      barriers seem to point to a high conformational adaptability of the prion
      protein. To investigate this structural plasticity, we studied here the
      aggregation pathways of the human prion peptide PrP82-146, a major component of
      the Gerstmann-Straussler-Scheinker amyloid disease. By Fourier transform infrared
      (FT-IR) spectroscopy, electron microscopy, and atomic force microscopy (AFM), we
      monitored the time course of PrP82-146 fibril formation. After incubation at 37
      degrees C, the unfolded peptide was found to aggregate into oligomers
      characterized by intermolecular beta-sheet infrared bands. At a critical oligomer
      concentration, the emergence of a new FT-IR band allowed to detect fibril
      formation. A different intermolecular beta-sheet interaction of the peptides in
      oligomers and in fibrils is, therefore, detected by FT-IR spectroscopy, which, in
      addition, suggests a parallel orientation of the cross beta-sheet structures of
      PrP82-146 fibrils. By AFM, a wide distribution of PrP82-146 oligomer volumes--the
      smallest ones containing from 5 to 30 peptides--was observed. Interestingly, the
      statistical analysis of AFM data enabled us to detect a quantization in the
      oligomer height values differing by steps of approximately 0.5 nm that could
      reflect an orientation of oligomer beta-strands parallel with the sample surface.
      Different morphologies were also detected for fibrils that displayed high
      heterogeneity in their twisting periodicity and a complex hierarchical assembly.
      Thermal aggregation of PrP82-146 was also investigated by FT-IR spectroscopy,
      which indicated for these aggregates an intermolecular beta-sheet interaction
      different from that observed for oligomers and fibrils. Unexpectedly, random
      aggregates, induced by solvent evaporation, were found to display a significant
      alpha-helical structure as well as several beta-sheet components. All these
      results clearly point to a high plasticity of the PrP82-146 peptide, which was
      found to be capable of undergoing several aggregation pathways, with end products
      displaying different secondary structures and intermolecular interactions.

PMID- 18619463
TI  - Topology conservation and loop flexibility in quadruplex-drug recognition:
      crystal structures of inter- and intramolecular telomeric DNA quadruplex-drug
      complexes.
AB  - Knowledge of the biologically relevant topology is critical for the design of
      drugs targeting quadruplex nucleic acids. We report here crystal structures of a
      G-quadruplex-selective ligand complexed with two human telomeric DNA
      quadruplexes. The intramolecular quadruplex sequence d[TAGGG(TTAGGG)(3)] and the
      bimolecular quadruplex sequence d(TAGGGTTAGGGT) were co-crystallized with a tetra
      substituted naphthalene diimide quadruplex-binding ligand. The structures were
      solved and refined to 2.10- and 2.20-A resolution, respectively, revealing that
      the quadruplex topology in both structures is unchanged by the addition of the
      ligands, retaining a parallel-stranded arrangement with external double-chain
      reversal propeller loops. The parallel topology results in accessible external 5'
      and 3' planar G-tetrad surfaces for ligand stacking. This also enables
      significant ligand-induced conformational changes in several TTA propeller loops
      to take place such that the loops themselves are able to accommodate bound drug
      molecules without affecting the parallel quadruplex topology, by stacking on the
      external TTA connecting loop nucleotides. Ligands are bound into the external TTA
      loop nucleotides and stack onto G-tetrad surfaces. These crystal structures
      provide a framework for further ligand development of the naphthalene diimide
      series to enhance selectivity and affinity.

PMID- 18619464
TI  - The effect of membranes on the in vitro fibrillation of an amyloidogenic light
      chain variable-domain SMA.
AB  - Light chain (or AL) amyloidosis is the most common form of systemic amyloidosis,
      characterized by the pathological deposition of insoluble fibrils of
      immunoglobulin light-chain fragments in various organs and tissues, especially in
      the kidney and heart. Both the triggering factors and the mechanisms involved in
      the abnormal formation of the insoluble fibrillar aggregates from the soluble
      proteins are poorly understood. For example, although the fibrillar deposits are
      typically found associated with the extracellular matrix and basement membranes,
      it is not clear whether fibrils are initially formed intra- or extracellularly,
      nor it is understood what determines where the deposits will occur; i.e., site
      tropism. In the present investigation, we studied the interaction of a
      recombinant amyloidogenic light-chain variable domain, SMA, with lipid vesicles.
      The nature of the interaction was dependent on the lipid composition and the SMA
      to lipid ratio. The most pronounced effect was found from vesicles composed of
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphate, which dramatically accelerated fibril growth. Interestingly, spectral
      probes, such as intrinsic fluorescence and far-UV CD spectroscopy did not show
      significant conformational changes in the presence of the vesicles. The presence
      of cholesterol or divalent cations, such as Ca(2+) and Mg(2+), lead to decreased
      membrane-induced SMA fibrillation. Thus, membranes may have significant effects
      on light-chain fibrillation and may contribute to the site selectivity observed
      in AL amyloidosis.

PMID- 18619465
TI  - Down-regulation of outer membrane proteins by noncoding RNAs: unraveling the cAMP
      CRP- and sigmaE-dependent CyaR-ompX regulatory case.
AB  - The sigma(E) (extracytoplasmic stress response sigma factor in Escherichia coli)
      signaling system of Gram-negative bacteria plays an essential role in the
      maintenance of the extracytoplasmic compartment. Upon induction of this system,
      approximately 100 genes are up-regulated. The majority of these genes encode
      proteins that participate in the synthesis, assembly, and homeostasis of outer
      membrane proteins and lipopolysaccharides. A second aspect of the sigma(E)
      response is a regulatory loop that prevents expression of the major porins.
      Misfolding or overproduction of most of these porins is sufficient to trigger the
      envelope stress response. Recent work indicates that small Hfq-binding RNAs play
      a major role in maintaining envelope homeostasis and, so far, two sigma(E)
      dependent small noncoding RNAs (sRNAs), MicA and RybB, have been shown to
      facilitate rapid removal of multiple omp transcripts in response to elevated
      activity of the alternative sigma factor. Here we report the identification of
      the sRNA (CyaR, cyclic AMP-activated RNA) that promotes decay of the ompX mRNA.
      The transcription of the cyaR gene is stringently controlled by cAMP-cAMP
      receptor protein and, unexpectedly, cyaR expression is also up-regulated,
      directly or indirectly, by sigma(E). In addition, this work identified MicA as a
      factor that cooperates in the negative control of ompX expression. The
      conservation of CyaR, MicA, RybB, and their targets suggests that the omp mRNA
      sRNA regulatory network is an integral part of the envelope stress response in
      many enterobacteria.

PMID- 18619466
TI  - Evolutionary history of a specialized p450 propane monooxygenase.
AB  - The evolutionary pressures that shaped the specificity and catalytic efficiency
      of enzymes can only be speculated. While directed evolution experiments show that
      new functions can be acquired under positive selection with few mutations, the
      role of negative selection in eliminating undesired activities and achieving high
      specificity remains unclear. Here we examine intermediates along the 'lineage'
      from a naturally occurring C12-C20 fatty acid hydroxylase (P450BM3) to a
      laboratory-evolved P450 propane monooxygenase (P450PMO) having 20 heme domain
      substitutions compared to P450BM3. Biochemical, crystallographic, and
      computational analyses show that a minimal perturbation of the P450BM3 fold and
      substrate-binding pocket accompanies a significant broadening of enzyme substrate
      range and the emergence of propane activity. In contrast, refinement of the
      enzyme catalytic efficiency for propane oxidation (approximately 9000-fold
      increase in kcat/Km) involves profound reshaping and partitioning of the
      substrate access pathway. Remodeling of the substrate-recognition mechanisms
      ultimately results in remarkable narrowing of the substrate profile around
      propane and enables the acquisition of a basal iodomethane dehalogenase activity
      as yet unknown in natural alkane monooxygenases. A highly destabilizing L188P
      substitution in a region of the enzyme that undergoes a large conformational
      change during catalysis plays an important role in adaptation to the gaseous
      alkane. This work demonstrates that positive selection alone is sufficient to
      completely respecialize the cytochrome P450 for function on a nonnative
      substrate.

PMID- 18619467
TI  - Characterization of conserved motifs in HIV-1 Vif required for APOBEC3G and
      APOBEC3F interaction.
AB  - Apolipoprotein B mRNA-editing catalytic polypeptide-like 3G (APOBEC3G, or A3G)
      and related cytidine deaminases such as apolipoprotein B mRNA-editing catalytic
      polypeptide-like 3F (APOBEC3F, or A3F) are potent inhibitors of retroviruses.
      Formation of infectious human immunodeficiency virus (HIV)-1 requires suppression
      of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3
      proteins through a common mechanism by recruiting Cullin5, ElonginB, and ElonginC
      E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome
      mediated degradation. Domains in Vif that mediate APOBEC3 recognition have not
      been fully characterized. In the present study, we identified a VxIPLx(4
      5)LxPhix(2)YWxL motif in HIV-1 Vif, which is required for efficient interaction
      between Vif and A3G, Vif-mediated A3G degradation and virion exclusion, and
      functional suppression of the A3G antiviral activity. Amino acids 52 to 72 of HIV
      1 Vif (including the VxIPLx(4-5)LxPhix(2)YWxL motif) alone could mediate
      interaction with A3G, and this interaction was abolished by mutations of two
      hydrophobic amino acids in this region. We have also observed that a Vif mutant
      was ineffective against A3G, yet it retained the ability to interact with Cullin5
      E3 ubiquitin complex and A3G, suggesting that interaction with A3G is necessary
      but not sufficient to inhibit its antiviral function. Unlike the previously
      identified motif of HIV-1 Vif amino acids 40 to 44, which is only important for
      A3G suppression, the VxIPLx(4-5)LxPhix(2)YWxL motif is also required for
      efficient A3F interaction and suppression. On the other hand, another motif,
      TGERxW, of HIV-1 Vif amino acids 74 to 79 was found to be mainly important for
      A3F interaction and inhibition. Both the VxIPLx(4-5)LxPhix(2)YWxL and TGERxW
      motifs are highly conserved among HIV-1, HIV-2, and various simian
      immunodeficiency virus Vif proteins. Our data suggest that primate lentiviral Vif
      molecules recognize their autologous APOBEC3 proteins through conserved
      structural features that represent attractive targets for the development of
      novel inhibitors.

PMID- 18619468
TI  - The PMS2 subunit of human MutLalpha contains a metal ion binding domain of the
      iron-dependent repressor protein family.
AB  - DNA mismatch repair (MMR) is responsible for correcting replication errors.
      MutLalpha, one of the main players in MMR, has been recently shown to harbor an
      endonuclease/metal-binding activity, which is important for its function in vivo.
      This endonuclease activity has been confined to the C-terminal domain of the
      hPMS2 subunit of the MutLalpha heterodimer. In this work, we identify a striking
      sequence-structure similarity of hPMS2 to the metal-binding/dimerization domain
      of the iron-dependent repressor protein family and present a structural model of
      the metal-binding domain of MutLalpha. According to our model, this domain of
      MutLalpha comprises at least three highly conserved sequence motifs, which are
      also present in most MutL homologs from bacteria that do not rely on the
      endonuclease activity of MutH for strand discrimination. Furthermore, based on
      our structural model, we predict that MutLalpha is a zinc ion binding protein and
      confirm this prediction by way of biochemical analysis of zinc ion binding using
      the full-length and C-terminal domain of MutLalpha. Finally, we demonstrate that
      the conserved residues of the metal ion binding domain are crucial for MMR
      activity of MutLalpha in vitro.

PMID- 18619469
TI  - Insights into the impact of histone acetylation and methylation on Sir protein
      recruitment, spreading, and silencing in Saccharomyces cerevisiae.
AB  - Silent chromatin formation in Saccharomyces cerevisiae begins with the
      recruitment of silent information regulator (Sir) proteins to silencers at the
      silent mating-type loci and to telomere ends. Next, Sir2/3/4 proteins propagate
      across these loci as histones are deacetylated by the NAD(+)-dependent histone
      deacetylase Sir2p, ultimately resulting in the cessation of transcription and in
      the loss of SET1- and DOT1-dependent methylation of histone H3 within silent
      chromatin. We analyzed the effects of modifiable lysine residues on histones H3
      and H4 on experimentally defined steps in silencing: recruitment of Sir proteins
      to silencers, Sir protein spreading, and transcriptional repression. Loss of
      acetylation, but not methylation, facilitated both Sir recruitment and spreading,
      and Sir spreading across hypoacetylated chromatin could disrupt SET1- and DOT1
      dependent histone methylation without silencing underlying genes. Our data
      indicate that loss of methylation of K4 and K79 on histone H3 reflects
      intermediate events during the formation of silent chromatin, and that retention
      of a positive charge at a single residue on histone H4 (K16) was both necessary
      and sufficient to permit Sir spreading beyond sites of their recruitment.

PMID- 18619471
TI  - Differential effects of diabetes induced by streptozotocin and that develops
      spontaneously on prostate growth in Bio Breeding (BB) rats.
AB  - We investigated molecular changes in the response to insulin in prostates of
      spontaneously developed (Bio Breeding) and streptozotocin (STZ)-induced diabetic
      rats that received sufficient amounts (euglycemic group), or suboptimal doses
      (hyperglycemic group) of insulin for 32 weeks, using Affymetrix GeneChip analysis
      of gene expression. Alterations in gene expression levels identified by
      microarray analysis, having potential biological relevance to prostate growth,
      were verified by real-time reverse transcription polymerase chain reaction (RT
      PCR). A significant decrease in the weight of ventral prostate was observed in
      the hyperglycemic STZ-induced but not spontaneously developed diabetic group.
      Microarray analysis revealed that gene expression profiles were distinctly
      different in each region of the prostate, and that hyperglycemic diabetes in
      spontaneously developed and STZ-diabetic rats was associated with differential
      changes in the prostatic expression levels of 856 genes, of which 35 were related
      to cell growth, proliferation and death. RT-PCR data verified significant
      differences in the mRNA expression levels of Igfbp6, Tieg, and Clu between
      euglycemic and hyperglycemic groups, whereas expression levels of these genes in
      control and euglycemic diabetic groups were not significantly different. In
      ventral prostate, the mRNA expression levels of Igfbp6 and Tieg were
      significantly higher in the hyperglycemic STZ-induced diabetic than in the
      hyperglycemic spontaneously diabetic BBDP/Wor rats. Our data demonstrate that the
      diabetes induced by STZ in the BBDR/Wor rats affects prostate growth and the
      molecular response to insulin differently than that observed in BBDP/Wor rats
      that develop diabetes spontaneously.

PMID- 18619470
TI  - The optimal burst of mutation to create a phenotype.
AB  - Mutagenesis is commonly applied to genes and genomes to create novel variants
      with desired properties. This paper calculates the level of mutagenesis that
      maximizes the appearance of favorable mutants, assuming that the mutagenesis is
      applied in a single episode. The downside of mutagenesis is that a substantial
      fraction of mutations will destroy gene/genome function. The upside of
      mutagenesis is the production of beneficial mutations, but the desired phenotype
      may require that 1, 2 or more beneficial mutations be present simultaneously (the
      phenotype dimensionality). The optimum level of mutagenesis is sensitive to both
      properties. In the simplest model, the mutation optimum occurs when number of
      lethal equivalents per genome equals the phenotype dimensionality, a result first
      derived by Mundry and Gierer [1958. Production of mutations in tobacco mosaic
      virus by chemical treatment of its nucleic acid in vitro. Z. Vererbungsl. 89 (4),
      614-630]. This level of mutation is shown to be an upper bound for the optimum in
      various extensions of the model, and the recovery of mutants is also reasonably
      tolerant to deviations from the optimum.

PMID- 18619472
TI  - Strikingly different penetrance of LHON in two Chinese families with primary
      mutation G11778A is independent of mtDNA haplogroup background and secondary
      mutation G13708A.
AB  - The penetrance of Leber's hereditary optic neuropathy (LHON) in families with
      primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and
      nuclear genetic background, as well as environmental factors, have been reported
      to be involved in different affected pedigrees. Here we describe two large
      Chinese families that show a striking difference in the penetrance of LHON, in
      which 53.3% and 15.0% of members were affected (P<0.02), respectively. Analysis
      of the complete mtDNA genome of the two families revealed the presence of the
      primary mutation G11778A and several other variants suggesting the same
      haplogroup status G2a. The family with higher penetrance contained a previously
      described secondary mutation G13708A, which presents a polymorphism in normal
      Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as
      described in a previous study. Evolutionary analysis failed to indicate any
      putatively pathogenic mutation that cosegregated with G11778A in these two
      pedigrees. Our results suggest that the variable penetrance of LHON in the two
      Chinese families is independent of both their mtDNA haplotype background and a
      secondary mutation G13708A. As a result, it is likely that unknown nuclear gene
      involvement and/or other factors contribute to the strikingly different
      penetrance of LHON.

PMID- 18619473
TI  - Peripheral administration of group III mGlu receptor agonist ACPT-I exerts
      potential antipsychotic effects in rodents.
AB  - Several lines of evidence implicate dysfunction of glutamatergic
      neurotransmission in the pathophysiology of schizophrenia. Previous behavioral
      studies have indicated that metabotropic glutamate (mGlu) receptors may be useful
      targets for the treatment of psychosis. It has been shown that agonists and
      positive allosteric modulators of group II mGlu receptors produce potential
      antipsychotic effects in behavioral models of schizophrenia in rodents. Group III
      mGlu receptors seem to be also promising targets for a variety of
      neuropsychiatric and neurodegenerative disorders. However, despite encouraging
      data in animal models, most ligands of group III mGlu receptors still suffer from
      weak affinities, incapacity to cross the blood-brain barrier or absence of full
      pharmacological characterization. These limitations slow down the validation
      process of group III mGlu receptors as therapeutic targets. In this work, we
      choose to study an agonist of group III mGlu receptors (1S,3R,4S)-1-aminocyclo
      pentane-1,3,4-tricarboxylic acid (ACPT-I) using intraperitoneal administration in
      three animal behavioral models predictive of psychosis or hallucinations. The
      results of the present study show that ACPT-I, given at doses of 10 or 30mg/kg,
      decreased MK-801-induced hyperlocomotion and at a dose of 100mg/kg decreased
      amphetamine-induced hyperlocomotion in rats. Furthermore, ACPT-I dose-dependently
      decreased DOI-induced head twitches in mice and suppresses DOI-induced frequency
      and amplitude of spontaneous EPSPs in slices from mouse brain frontal cortices.
      These data demonstrate that ACPT-I is a brain-penetrating compound and
      illustrates its promising therapeutic role for the treatment of schizophrenia.

PMID- 18619475
TI  - Depression of spinal network activity by thiopental: shift from phasic to tonic
      GABA(A) receptor-mediated inhibition.
AB  - Interneuronal networks in the spinal ventral horn are plausible substrates for
      mediating anesthetic-induced immobility. Here, we investigated how their activity
      is affected by clinically relevant concentrations of thiopental, a barbiturate in
      clinical use. In cultured spinal cord slices from mice, thiopental reduced action
      potential activity with an EC(50) of 16.6+/-2.4microM. Recordings of GABA(A) and
      glycine receptor-mediated inhibitory currents indicated that the effect was
      largely mediated by GABA(A) receptors and that glycine receptors were not
      relevant targets. Specifically, 20microM thiopental prolonged the decay time of
      spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) more than
      twofold. Although this prolongation of decay time increased the inhibitory charge
      per sIPSC the concomitant strong reduction of sIPSC frequency resulted in less
      inhibitory current entering the neurons via this route. However, 20microM
      thiopental also induced a tonic current of 30+/-10pA, mediated by GABA(A)
      receptors; 50microM thiopental nearly abolished sIPSC activity but augmented
      tonic currents to 69+/-14pA. Furthermore, at this concentration, activity
      depressing mechanisms independent of GABA(A) receptors came into play. The
      results suggest that in the spinal ventral horn thiopental acts mostly, but not
      exclusively, via GABA(A) receptors. With increasing concentrations of the drug,
      inhibition via sIPSCs is limited by negative feedback on interneuronal firing
      whereas action potential-independent GABAergic inhibition due to tonic currents
      gains progressively in impact.

PMID- 18619474
TI  - Individual differences in the attribution of incentive salience to reward-related
      cues: Implications for addiction.
AB  - Drugs of abuse acquire different degrees of control over thoughts and actions
      based not only on the effects of drugs themselves, but also on predispositions of
      the individual. Those individuals who become addicted are unable to shift their
      thoughts and actions away from drugs and drug-associated stimuli. Thus in
      addicts, exposure to places or things (cues) that has been previously associated
      with drug-taking often instigates renewed drug-taking. We and others have
      postulated that drug-associated cues acquire the ability to maintain and
      instigate drug-taking behavior in part because they acquire incentive
      motivational properties through Pavlovian (stimulus-stimulus) learning. In the
      case of compulsive behavioral disorders, including addiction, such cues may be
      attributed with pathological incentive value ("incentive salience"). For this
      reason, we have recently begun to explore individual differences in the tendency
      to attribute incentive salience to cues that predict rewards. When discrete cues
      are associated with the non-contingent delivery of food or drug rewards some
      animals come to quickly approach and engage the cue even if it is located at a
      distance from where the reward will be delivered. In these animals the reward
      predictive cue itself becomes attractive, eliciting approach towards it,
      presumably because it is attributed with incentive salience. Animals that develop
      this type of conditional response are called "sign-trackers". Other animals,
      "goal-trackers", do not approach the reward-predictive cue, but upon cue
      presentation they immediately go to the location where food will be delivered
      (the "goal"). For goal-trackers the reward-predictive cue is not attractive,
      presumably because it is not attributed with incentive salience. We review here
      preliminary data suggesting that these individual differences in the tendency to
      attribute incentive salience to cues predictive of reward may confer
      vulnerability or resistance to compulsive behavioral disorders, including
      addiction. It will be important, therefore, to study how environmental,
      neurobiological and genetic interactions determine the extent to which
      individuals attribute incentive value to reward-predictive stimuli.

PMID- 18619476
TI  - Amelioration of recognition memory impairment associated with iron loading or
      aging by the type 4-specific phosphodiesterase inhibitor rolipram in rats.
AB  - Increasing evidence indicates that iron deposition in the brain might play a role
      in cognitive dysfunction associated with neurodegenerative disorders and aging.
      Previous studies have not examined whether iron-induced memory deficits can be
      attenuated by acute treatments with memory-enhancing agents. Phosphodiesterase
      type 4 (PDE4) inhibitors such as rolipram (ROL) ameliorate memory impairments in
      several rodent models of amnesia and have been proposed as candidate cognitive
      enhancing drugs. Here we show that a single posttraining systemic injection of
      ROL dose-dependently attenuates the impairment of memory for novel object
      recognition (NOR) in rats given neonatal iron loading, a model of iron-induced
      cognitive impairment. Posttraining administration of ROL also recovered NOR
      deficits associated with aging in rats. These findings provide the first evidence
      that stimulation of an intracellular second messenger signaling pathway can
      attenuate iron-induced memory impairment, and support the view that PDE4
      inhibitors might ameliorate cognitive dysfunction associated with aging and
      neurodegenerative disorders.

PMID- 18619477
TI  - Intra-individual variability in ADHD, autism spectrum disorders and Tourette's
      syndrome.
AB  - The potential for response variability to serve as an endophenotype for attention
      deficit hyperactivity disorders (ADHD) rests, in part, upon the development of
      reliable and valid methods to decompose variability. This study investigated the
      specificity of intra-individual variability (IIV) in 53 children with ADHD by
      comparing them with 25 children with high functioning autism (HFA), 32 children
      with autism spectrum disorders (ASD), who also were comorbid for ADHD (ASD+ADHD),
      21 children with Tourette's syndrome (TS), and 85 typically developing controls
      (TD). In order to decompose the variability of the reaction times, we applied
      three distinct techniques: ex-Gaussian modeling, intra-individual variability
      analysis, and spectral analysis. Our data revealed that children with HFA and
      children with ASD+ADHD exhibited substantial IIV compared with ADHD and TD
      children. We argue that: (1) all three methods lead to a single consistent
      conclusion; (2) careful documentation of the analytic steps used in spectral
      analysis is mandatory for comparison between studies; (3) the presence of
      comorbidities may constitute an important factor in the observed response
      variability in previous studies of ADHD.

PMID- 18619479
TI  - Parameterization of Keeling's network generation algorithm.
AB  - Simulation is increasingly being used to examine epidemic behaviour and assess
      potential management options. The utility of the simulations rely on the ability
      to replicate those aspects of the social structure that are relevant to epidemic
      transmission. One approach is to generate networks with desired social
      properties. Recent research by Keeling and his colleagues has generated simulated
      networks with a range of properties, and examined the impact of these properties
      on epidemic processes occurring over the network. However, published work has
      included only limited analysis of the algorithm itself and the way in which the
      network properties are related to the algorithm parameters. This paper identifies
      some relationships between the algorithm parameters and selected network
      properties (mean degree, degree variation, clustering coefficient and
      assortativity). Our approach enables users of the algorithm to efficiently
      generate a network with given properties, thereby allowing realistic social
      networks to be used as the basis of epidemic simulations. Alternatively, the
      algorithm could be used to generate social networks with a range of property
      values, enabling analysis of the impact of these properties on epidemic
      behaviour.

PMID- 18619478
TI  - Evidence that dopamine within motivation and song control brain regions regulates
      birdsong context-dependently.
AB  - Vocal communication is critical for successful social interactions among
      conspecifics, but little is known about how the brain regulates context
      appropriate communication. The neurotransmitter dopamine (DA) is involved in
      modulating highly motivated, goal-directed behaviors (including sexually
      motivated singing behavior), and emerging data suggest that the role of DA in
      vocal communication may differ depending on the context in which it occurs. To
      address this possibility, relationships between immunolabeled tyrosine
      hydroxylase (TH, the rate-limiting enzyme in catecholamine synthesis) and song
      produced within versus outside of a breeding context were explored in male
      European starlings (Sturnus vulgaris). Immunocytochemistry for dopamine beta
      hydroxylase (DBH; the enzyme that converts DA to norepinephrine) was also
      performed to provide insight into whether relationships between song and TH
      immunoreactivity reflected dopaminergic or noradrenergic neurotransmission.
      Measures of TH and DBH were quantified in song control regions (HVC, Area X,
      robust nucleus of the acropallium) and regions implicated in motivation (medial
      preoptic nucleus (POM), ventral tegmental area (VTA), and midbrain central gray).
      In Area X, POM, and VTA measures of TH correlated with song produced within, but
      not outside of a breeding context. DBH in these regions did not correlate with
      song in either context. Together, these data suggest DA in both song control and
      motivation brain regions may be more tightly linked to the regulation of highly
      goal-directed, sexually motivated vocal behavior.

PMID- 18619480
TI  - Envenoming by the viperid snake Proatheris superciliaris: a case report.
AB  - Snake bites caused by viperid snakes of Atheris genus are extremely rare,
      envenoming of a bite of related viper Proatheris superciliaris was described only
      once in the literature. The present case study depicts the envenoming of a 57
      years old Czech man, a private herpetologist, who was bitten to his finger. He
      developed painful local reaction, nausea, hematuria, hypertension, chest and
      lumbar pain. Coagulopathy and thrombocytopenia subsequently developed as well as
      acute renal failure, hepatic and lung lesion. Intensive care therapy was purely
      symptomatic and supportive as no antisera exists. Treatment included
      haemodialysis, substitution of fresh frozen plasma and platelets. Patient
      completely recovered during 1 month.

PMID- 18619482
TI  - Ambiguities and conventions in the perception of visual art.
AB  - Vision perception is ambiguous and visual arts play with these ambiguities. While
      perceptual ambiguities are resolved with prior constraints, artistic ambiguities
      are resolved by conventions. Is there a relationship between priors and
      conventions? This review surveys recent work related to these ambiguities in
      composition, spatial scale, illumination and color, three-dimensional layout,
      shape, and movement. While most conventions seem to have their roots in
      perceptual constraints, those conventions that differ from priors may help us
      appreciate how visual arts differ from everyday perception.

PMID- 18619481
TI  - A rational nomenclature for naming peptide toxins from spiders and other venomous
      animals.
AB  - Molecular toxinology research was initially driven by an interest in the small
      subset of animal toxins that are lethal to humans. However, the realization that
      many venomous creatures possess a complex repertoire of bioactive peptide toxins
      with potential pharmaceutical and agrochemical applications has led to an
      explosion in the number of new peptide toxins being discovered and characterized.
      Unfortunately, this increased awareness of peptide-toxin diversity has not been
      matched by the development of a generic nomenclature that enables these toxins to
      be rationally classified, catalogued, and compared. In this article, we introduce
      a rational nomenclature that can be applied to the naming of peptide toxins from
      spiders and other venomous animals.

PMID- 18619483
TI  - Gender difference in the relationships between vision and hearing impairments and
      negative well-being.
AB  - OBJECTIVES: To evaluate the association of hearing impairment, vision impairment
      and their combination (dual sensory impairment) with negative well-being such as
      depression, subjective poor health and the reduced functional ability in
      community-dwelling older adults, and to determine whether any association varies
      by gender. METHODS: Between 2005 and 2006, we objectively examined vision and
      hearing impairment (using best-corrected visual acuity and pure-tone audiometric
      test) in 843 people aged 65 years and older (351 males, 492 females) in a rural
      Japanese town. Through a home visit interview survey using a structured
      questionnaire, we also collected information on depression (the five-item
      Geriatric Depression Scale), subjective poor health, and reduced functional
      activity (the Tokyo Metropolitan Institute of Gerontology's Index of Competence).
      RESULTS: We observed gender differences in the association between sensory
      impairment and depression. Multiple logistic regression analysis revealed that
      hearing impairment in males (adjusted odds ratio: 2.22, 95% confidence interval;
      1.07-4.61) and vision impairment in females (1.91, 1.14-3.21) were related to
      depression. Vision impairment and dual sensory impairment were also associated
      with subjective poor health and reduced functional activity in both sexes.
      CONCLUSIONS: Sensory impairment is significantly associated with negative well
      being in older persons, and its association with depression may differ between
      males and females.

PMID- 18619484
TI  - The use of solid lipid nanoparticles to target a lipophilic molecule to the liver
      after intravenous administration to mice.
AB  - Taspine solid lipid nanoparticles (Ta-SLN) and taspine solid lipid nanoparticles
      modified by galactoside (Ta-G2SLN) were prepared by the film evaporation
      extrusion method. The nanoparticles were spherical or near-spherical particles
      with smooth surface, small size and high encapsulation efficiency. Ta-G2SLN and
      Ta-SLN showed significant inhibition on 7721 cell growth. Intravenous injection
      of either Ta-SLN or Ta-G2SLN resulted in a higher plasma and liver concentration
      and a longer retention time in mice compared with the administration of Ta. These
      results suggested that SLN tended to be preferentially delivered to the liver and
      Ta-G2SLN may further enhance liver targeting.

PMID- 18619485
TI  - An Australian webspinner species makes the finest known insect silk fibers.
AB  - Aposthonia gurneyi, an Australian webspinner species, is a primitive insect that
      constructs and lives in a silken tunnel which screens it from the attentions of
      predators. The insect spins silk threads from many tiny spines on its forelegs to
      weave a filmy sheet. We found that the webspinner silk fibers have a mean
      diameter of only 65 nm, an order of magnitude smaller than any previously
      reported insect silk. The purpose of such fine silk may be to reduce the
      metabolic cost of building the extensive tunnels. At the molecular level, the A.
      gurneyi silk has a predominantly beta-sheet protein structure. The most abundant
      clone in a cDNA library produced from the webspinner silk glands encoded a
      protein with extensive glycine-serine repeat regions. The GSGSGS repeat motif of
      the A. gurneyi silk protein is similar to the well-known GAGAGS repeat motif
      found in the heavy fibroin of silkworm silk, which also has beta-sheet structure.
      As the webspinner silk gene is unrelated to the silk gene of the phylogenetically
      distant silkworm, this is a striking example of convergent evolution.

PMID- 18619486
TI  - The effect of age and telomere length on immune function in the horse.
AB  - Telomeres, specialized structures present at the ends of linear eukaryotic
      chromosomes, function to maintain chromosome stability and integrity. Telomeres
      shorten with each cell division eventually leading to replicative senescence, a
      process thought to be associated with age-related decline in immune function. We
      hypothesized that shortened PBMC telomere length is a factor contributing to
      immunosenescence of the aged horse. Telomere length was assessed in 19 horses
      ranging in age from 1 to 25 years. Mitogen-induced 3H-thymidine incorporation,
      total serum IgG, and pro-inflammatory cytokine expression was also determined for
      each horse. Relative telomere length (RTL) was highly correlated with overall
      age. RTL was positively correlated with 3H-thymidine incorporation and total IgG.
      Expression of pro-inflammatory cytokines was negatively correlated with RTL.
      These measures were also correlated with age, as expected. However, RTL was not
      correlated with immunosenescence and inflammaging in the oldest horse.

PMID- 18619487
TI  - Animal models of human psychopathology based on individual differences in novelty
      seeking and anxiety.
AB  - The role of individual factors in behavioural neuroscience is an important, but
      still neglected area of research. The present review aims to give, first, an
      outline of the most elaborated theory on animal behaviour, and second, an
      overview of systematic approaches of historic and present animal models of human
      psychopathology based on individual differences. This overview will be focused on
      animal models of unselected subjects (i.e. natural variance of a specific
      behaviour within a given population) and selected breeding for a specific
      behaviour. Accordingly, an outline of the personality model from Gray and
      McNaughton of individual behaviour in animals is given first. Then, a
      comprehensive overview of past and current animal models in novelty-seeking (i.e.
      psychomotor activation and exploration behaviour) based on systematic individual
      differences and its relationship to addiction is presented. Third, this will be
      followed by a comprehensive overview of individual differences in previous and
      present animal models for anxiety. Finally, critical aspects of such approaches
      in animal research are discussed, and suggestions are given where to go from
      here.

PMID- 18619488
TI  - Docosahexaenoic acid may act as a neuroprotector for methylmercury-induced
      neurotoxicity in primary neural cell cultures.
AB  - The ability of docosahexaenoic acid (DHA) to modulate methylmercury (MeHg)
      induced neurotoxicity was investigated in primary astrocytes and neurons from the
      cerebellum. Gas chromatography measurements indicated increased DHA content in
      both cell types after 24h supplementation. After individual or combined treatment
      with MeHg (10microM) and DHA (30 and 90microM), the cell-associated MeHg
      measurements were done using (14)C-labelled MeHg. In addition, mitochondrial
      activity was evaluated by MTT reduction, glutathione (GSH) content was measured
      with the fluorescent indicator monochlorobimane (MCB) and reactive oxygen species
      (ROS) were detected with the fluorescent indicator-chloro methyl derivative of di
      chloro di-hydro fluorescein diacetate (CMH(2)DCFDA). For all the tested
      treatments, i.e. DHA, MeHg or DHA+MeHg treatment, the neurons differed
      significantly (p<0.001) from astrocytes exhibiting increased ROS production and
      decreased MTT activity. After MeHg and 30microM DHA treatment there were no
      changes in MTT or GSH content but significant decrease (p<0.001) in ROS was
      observed in both the cell types when compared to MeHg alone. The cell-associated
      MeHg measurements indicated reduced MeHg-accumulation in both cell types (p<0.05)
      upon 30microM DHA exposure. Taken together, this study, for the first time
      establishes that DHA pretreatment effectively reduces cell-associated MeHg and
      prooxidant response from MeHg in both cerebellar astrocytes and neurons and thus
      supports the hypothesis that fish-derived nutrients offer possible
      neuroprotection from MeHg.

PMID- 18619489
TI  - Angiotensin II: a hormone involved in and contributing to pro-hypertrophic
      cardiac networks and target of anti-hypertrophic cross-talks.
AB  - Angiotensin II (Ang II) plays a major role in the progression of myocardial
      hypertrophy to heart failure. Inhibiting the angiotensin converting enzyme (ACE)
      or blockade of the corresponding Ang II receptors is used extensively in clinical
      practice, but there is scope for refinement of this mode of therapy. This review
      summarizes the current understanding of the direct effects of Ang II on
      cardiomyocytes and then focus particularly on interaction of components of the
      renin-angiotensin system with other hormones and cytokines. New findings
      described in approximately 400 papers identified in the PubMed database and
      published during the 2.5 years are discussed in the context of previous relevant
      literature. The cardiac action of Ang II is influenced by the activity of
      different isoforms of ACE leading to different amounts of Ang II by comparison
      with other angiotensinogen-derived peptides. The effect of Ang II is mediated by
      at least two different AT receptors that are differentially expressed in
      cardiomyocytes from neonatal, adult and failing hearts. The intracellular effects
      of Ang II are influenced by nitric oxide (NO)/cGMP-dependent cross talk and are
      mediated by the release of autocrine factors, such as transforming growth factor
      (TGF)-beta1 and interleukin (IL)-6. Besides interactions with cytokines, Ang II
      is involved in systemic networks including aldosterone, parathyroid hormone and
      adrenomedullin, which have their own effects on cardiomyocytes that modify,
      amplify or antagonize the primary effect of Ang II. Finally, hyperinsulemia and
      hyperglycaemia influence Ang II-dependent processes in diabetes and its cardiac
      sequelae.

PMID- 18619490
TI  - Spike sorting with hidden Markov models.
AB  - The ability to detect and sort overlapping spike waveforms in extracellular
      recordings is key to studies of neural coding at high spatial and temporal
      resolution. Most spike-sorting algorithms are based on initial spike detection
      (e.g. by a voltage threshold) and subsequent waveform classification. Much effort
      has been devoted to the clustering step, despite the fact that conservative spike
      detection is notoriously difficult in low signal-to-noise conditions and often
      entails many spike misses. Hidden Markov models (HMMs) can serve as generative
      models for continuous extracellular data records. These models naturally combine
      the spike detection and classification steps into a single computational
      procedure. They unify the advantages of independent component analysis (ICA) and
      overlap-search algorithms because they blindly perform source separation even in
      cases where several neurons are recorded on a single electrode. We apply HMMs to
      artificially generated data and to extracellular signals recorded with glass
      electrodes. We show that in comparison with state-of-art spike-sorting
      algorithms, HMM-based spike sorting exhibits a comparable number of false
      positive spike classifications but many fewer spike misses.

PMID- 18619491
TI  - A novel system for recording from single neurons in unrestrained animals.
AB  - To observe neural activity in animals engaged in natural behavior, it is often
      desirable to minimize or eliminate restraint of the animal. We have developed a
      simple system for recording from single units in unrestrained cats. An implant
      with multiple guide tubes and a tiny microdrive is placed inside the recording
      chamber. An indwelling Pt-Ir microelectrode is advanced incrementally during
      recording sessions that occur over a period of weeks or months. Electrodes can be
      easily replaced. We obtain excellent recording stability, and also have been able
      to sample extensively from a region of cortex or brain stem in a single animal.
      The essential electronics have been miniaturized and sewn into a light-weight
      walking jacket, so that we can collect data from a cat who is not connected to
      any fixed equipment.

PMID- 18619492
TI  - Evaluation of genomic regions of hepatitis A virus for phylogenetic analysis:
      Suitability of the 2C region for genotyping.
AB  - The use of different genomic fragments of hepatitis A virus (HAV) has been
      described for classification of strains available globally. However, the
      limitations of these fragments have been reported in several studies. The present
      study was conducted to evaluate the genomic fragments of HAV, spanning from the
      5'NCR to 3'NCR to employ them in molecular diagnosis and genotyping. The
      different phylogenetic methods confirmed the use of the 5'NCR and the VP4 region
      in diagnosis due to their conserved nature. The entire genome, 2A, 2C and 3D were
      identified as the suitable genomic regions comparable to the VP1 region
      recommended earlier for genotyping. Likelihood mapping analysis indicated the
      full-length genome sequence as the region of choice for genotyping of HAV. This
      was followed by a short 2C region (1005nt), which needs to be explored.

PMID- 18619494
TI  - Association study of the cytochrome P450 17 gene polymorphism with personality
      traits in healthy subjects.
AB  - There have been several studies suggesting that sex hormones are involved in
      characterization of human mental function and behaviour. Recently, it has been
      reported that the -34T/C polymorphism of cytochrome P450 17 (CYP17) gene affects
      sex hormone dispositions. Therefore, it is possible that the CYP17 -34T/C
      polymorphism affects personality traits. In the present study, the association of
      this genetic polymorphism with personality traits was examined in 595 healthy
      Japanese. Personality traits were assessed by the Temperament and Character
      Inventory (TCI), and the CYP17 -34T/C polymorphism was detected by a PCR-RFLP
      method. In males, the scores of novelty seeking, cooperativeness, and self
      transcendence were higher in the group with the C allele than in that without
      this allele. In females, none of the seven TCI dimensions was different between
      the two genotype groups. The present study thus suggests that the -34T/C
      polymorphism of the CYP17 gene affects personality traits of healthy males, but
      not females, and this gender-dependent effect may be mediated by the action of
      sex hormones such as estradiol and testosterone.

PMID- 18619493
TI  - Mouse models of dengue virus infection and disease.
AB  - Dengue virus (DENV) causes the most significant mosquito-borne viral disease in
      the world in terms of illness, death, and economic cost, due to the lack of an
      approved vaccine or antiviral. Infections with one of the four serotypes of DENV
      (DENV1-4) can result in diseases ranging from an acute, self-limiting febrile
      illness (dengue fever, DF) to life-threatening dengue hemorrhagic fever (DHF) or
      dengue shock syndrome (DSS), yet exactly how viral and host factors contribute to
      the severe disease is unknown. Clinical observations have provided information on
      DENV pathogenesis, but the lack of an adequate animal model has hindered research
      on this important human pathogen. A mouse model is ideal for investigating host
      pathogen interactions due to the immunological tools available, however, wild
      type mice are resistant to DENV-induced disease. Therefore, the mouse models for
      DENV infection developed to date include infection of severely immunocompromised
      mice, non-physiologic routes of infection, and mouse-human chimeras, which all
      have their limitations. An inbred mouse model in which mice develop signs of
      human DENV-induced disease is needed to investigate the contribution of various
      immune components to protection and pathogenesis of DENV infections, and to test
      the efficacy of DENV vaccines and antivirals.

PMID- 18619495
TI  - Protein Ser/Thr phosphatases of parasitic protozoa.
AB  - Protein phosphorylation is an important mechanism implicated in physiology of any
      organism, including parasitic protozoa. Enzymes that control protein
      phosphorylation (kinases and phosphatases) are considered promising targets for
      drug development. This review attempts to provide the first account of the
      current understanding of the structure, regulation and biological functions of
      protein Ser/Thr phosphatases in unicellular parasites. We have examined the
      complements of phosphatases ("phosphatomes") of the PPP and PPM families in
      several species of Apicomplexa (including malaria parasite Plasmodium), as well
      as Giardia lamblia, Entamoeba histolytica, Trichomonas vaginalis and a
      microsporidium Encephalitozoon cuniculi. Apicomplexans have homologues (in most
      cases represented by single isoforms) of all human PPP subfamilies. Some
      apicomplexan PPP phosphatases have no orthologues in their vertebrate hosts,
      including a previously unrecognised group of pseudo-phosphatases with putative
      Ca(2+)-binding domains, which we designate as EFPP. We also describe the presence
      of previously undetected Zn finger motifs in PPEF phosphatases from
      kinetoplastids, and a likely case of convergent evolution of tetratricopeptide
      repeat domain-containing phosphatases in G. lamblia. Among the parasites
      examined, E. cuniculi has the smallest Ser/Thr phosphatome (5 PPP and no PPM),
      while T. vaginalis shows the largest expansion of the PPP family (169 predicted
      phosphatases). Most protozoan PPM phosphatases cluster separately from human
      sequences. The structural peculiarities or absence of human orthologues of a
      number of protozoan protein Ser/Thr phosphatases makes them potentially suitable
      targets for chemotherapy and thus warrants their functional assessment.

PMID- 18619496
TI  - Inhibitory effect of somatostatin on prostaglandin E2 synthesis by primary
      neonatal rat glial cells.
AB  - Glial inflammation plays an integral role in the development of neurodegenerative
      disease. Although somatostatin is known to be a local anti-inflammatory factor in
      the periphery, evidence of a similar function in the brain is scarce. The aim of
      the present study was to investigate the effect of somatostatin on prostaglandin
      E(2) synthesis in primary neonatal rat glial cells. The data shows that high
      concentrations of somatostatin (10(-5)-10(-4)) significantly increased
      prostaglandin synthesis. By contrast, when used at physiologically relevant
      concentrations (10(-9)-10(-7) M), somatostatin and somatostatin receptor agonists
      decreased prostaglandin E(2) synthesis in non-stimulated glial cells as well as
      in lipopolysaccharide-induced prostaglandin synthesis. The inhibitory effect of
      somatostatin in lipopolysaccharide-treated cells could be mimicked by protein
      kinase A inhibitor and was prevented by forskolin. These observations suggest the
      presence of a novel neuro-immune feedback pathway through which somatostatin
      inhibits glial prostaglandin synthesis, and thus may prove to play a role in
      brain inflammation. This action of somatostatin may have a therapeutic potential
      in pathological conditions of the brain, where an inflammatory response is
      involved.

PMID- 18619497
TI  - HDAC1/HDAC3 modulates PPARG2 transcription through the sumoylated CEBPD in
      hepatic lipogenesis.
AB  - CCAAT/Enhancer binding proteins (C/EBPs) and peroxisome proliferator-activated
      receptors gamma (PPARG) play critical roles in the regulation of lipid metabolism
      genes. Overexpression of CEBPdelta (CEBPD) enhances lipid accumulation and
      specifically activates PPARG2 transcription in HepG2 cells. By using 5'-serial
      deletion reporter analysis, we show that the region comprising the -457 to +129
      base pairs is required for CEBPD response of the PPARG2 promoter. Two critical
      CEBPD-binding motifs on the -324/-311 and -158/-145 of human PPARG2 promoter are
      identified. We previously have shown that the human CEBPD is sumoylated by small
      ubiquitin-related modifier-1 (SUMO1). We further demonstrated that the
      sumoylation of CEBPD lysine 120 is also detectable in HepG2 cells, and this
      modification functions for binding of the recruits, HDAC1 and HDAC3. Meanwhile,
      an in vivo chromatin IP assay demonstrated that the sumoylation mutant of CEBPD
      lost a significant portion of HDAC1 and HDAC3 interaction. Combining that the
      increasing amount of CEBPD and the sumoylated CEBPD (suCEBPD) consistently
      responded to lipogenic stimulation, these results suggest that the excess non
      sumoylated CEBPD could be a critical activator which reverses suCEBPD/HDAC1/HDAC3
      mediated PPARG2 gene inactivation and promotes hepatic lipogenesis. Taken
      together, we suggest that suCEBPD/HDAC1/HDAC3 complex inactivates PPARG2
      transcription, and the induction of CEBPD expression transiently activates PPARG2
      transcription which is involved in adipocyte-like lipogenesis in HepG2 cells.

PMID- 18619498
TI  - Inclusion bodies: specificity in their aggregation process and amyloid-like
      structure.
AB  - The accumulation of aggregated protein in the cell is associated with the
      pathology of many diseases and constitutes a major concern in protein production.
      Intracellular aggregates have been traditionally regarded as nonspecific
      associations of misfolded polypeptides. This view is challenged by studies
      demonstrating that, in vitro, aggregation often involves specific interactions.
      However, little is known about the specificity of in vivo protein deposition.
      Here, we investigate the degree of in vivo co-aggregation between two self
      aggregating proteins, Abeta42 amyloid peptide and foot-and-mouth disease virus
      VP1 capsid protein, in prokaryotic cells. In addition, the ultrastructure of
      intracellular aggregates is explored to decipher whether amyloid fibrils and
      intracellular protein inclusions share structural properties. The data indicate
      that in vivo protein aggregation exhibits a remarkable specificity that depends
      on the establishment of selective interactions and results in the formation of
      oligomeric and fibrillar structures displaying amyloid-like properties. These
      features allow prokaryotic Abeta42 intracellular aggregates to act as effective
      seeds in the formation of Abeta42 amyloid fibrils. Overall, our results suggest
      that conserved mechanisms underlie protein aggregation in different organisms.
      They also have important implications for biotechnological and biomedical
      applications of recombinant polypeptides.

PMID- 18619500
TI  - Bacillus thuringiensis improved isolation methodology from soil samples.
AB  - Bacillus thuringiensis is a sporulating bacterium, which produces parasporal
      inclusions toxic to insects. Widely used methodologies to isolate Bt from soil
      consist of a thermal shock treatment followed by selective germination of spores.
      The results presented here suggest that a preliminary 5 h dry-heat treatment
      largely enhance the selectivity of these procedures.

PMID- 18619499
TI  - Antibiotic marker modifications of lambda Red and FLP helper plasmids, pKD46 and
      pCP20, for inactivation of chromosomal genes using PCR products in multidrug
      resistant strains.
AB  - The Red recombinase system of bacteriophage Lambda has been used to inactivate
      chromosomal genes in bacteria using PCR products. In this study, we describe the
      replacement of the ampicillin resistance marker of helper plasmids pKD46 and
      pCP20 by a gentamicin resistance gene to disrupt chromosomal genes and then to
      eliminate FRT flanked resistance gene in multiple antibiotic-resistant Salmonella
      enterica strains.

PMID- 18619501
TI  - Functional depletion of capsaicin-sensitive primary afferent fibers attenuates
      rat pain-related behaviors and paw edema induced by the venom of scorpion Buthus
      martensi Karch.
AB  - The role of capsaicin-sensitive primary afferent fibers in rat pain-related
      behaviors and paw edema induced by scorpion Buthus martensi Karch (BmK) venom was
      investigated in this study. It was found that functional depletion of capsaicin
      sensitive primary afferent fibers with a single systemic injection of
      resiniferatoxin (RTX) dramatically decreased spontaneous nociceptive behaviors,
      prevented the development of primary mechanical and thermal hyperalgesia as well
      as mirror-image mechanical hyperalgesia. RTX treatment significantly attenuated
      BmK venom-induced c-Fos expression in all laminaes of bilateral L4-L5 lumbar
      spinal cord, especially in superficial laminaes. Moreover, RTX treatment markedly
      reduced the early paw edema induced by BmK venom. Thus, the results indicate that
      capsaicin-sensitive primary afferent fibers play a critical role in various pain
      related behaviors and paw edema induced by BmK venom in rats.

PMID- 18619502
TI  - Fast degrading polyesters as siRNA nano-carriers for pulmonary gene therapy.
AB  - A potential siRNA carrier for pulmonary gene delivery was assessed by
      encapsulating siRNA into biodegradable polyester nanoparticles consisting of
      tertiary-amine-modified polyvinyl alcohol (PVA) backbones grafted to poly(d,l
      lactide-co-glycolide) (PLGA). The resulting siRNA nanoparticles were prepared
      using a solvent displacement method that offers the advantage of forming small
      nanoparticles without using shear forces. The nanoparticles were characterized
      with regard to particle size, zeta-potential, and degradation at pH 7.4 using
      dynamic and static light scattering. SiRNA release studies were performed and
      correlated to the nanoparticle degradation. In vitro knockdown of firefly
      luciferase reporter gene was used to assess the potential of the nanoparticles as
      siRNA carriers in a human lung epithelial cell line, H1299 luc. The amine
      modified-PVA-PLGA/siRNA nanoparticles form 150-200 nm particles with zeta
      potentials of +15-+20 mV in phosphate buffered saline (PBS). Break down of the
      nanoparticles was seen within 4 h in PBS with sustained release of siRNA. These
      nanoparticles have achieved 80-90% knockdown of a luciferase reporter gene with
      only 5 pmol anti-luc siRNA, even after nebulization. Hence we conclude that amine
      modified-PVA-PLGA/siRNA nanoparticles could be a promising siRNA carrier for
      pulmonary gene delivery due to their fast degradation and potent gene knockdown
      profile.

PMID- 18619504
TI  - The tempting effect of forbidden foods. High calorie content evokes conflicting
      implicit and explicit evaluations in restrained eaters.
AB  - In this study, restrained and unrestrained eaters' immediate evaluations of high
      calorie content and low calorie content were measured, both when being deprived
      of food and when satiated. As an indirect measure, the Extrinsic Affective Simon
      Task (EAST) [De Houwer, J. (2003). The Extrinsic Affective Simon Task.
      Experimental Psychology, 50, 77-85.] was used. Explicit attitudes towards high
      calorie content and low calorie content were also assessed. Food deprivation was
      found to boost the value of food for all subjects on an impulsive level of
      information processing. More importantly, it was also found that restrained
      eaters exhibit a dissociative pattern of positive implicit and negative explicit
      attitudes towards high calorie content, but not towards low calorie content.
      Furthermore, restrained eaters evaluated high calorie content more negative than
      unrestrained eaters on an explicit level, but more positive on an implicit level.
      Results from this study are twofold. First, they suggest that conflicting
      evaluative reactions from two systems of information processing may play a
      central role in the restrained eater's dilemma. Second, individual differences
      between restrained and unrestrained eaters' attitudes towards high calorie
      content should further be investigated.

PMID- 18619503
TI  - Reversal of oxidative stress in endothelial cells by controlled release of
      adiponectin.
AB  - Hyperglycemia causes endothelial dysfunction due to its effect on increasing
      reactive oxygen species (ROS). Adiponectin (Adp) has been reported to suppress
      hyperglycemia-associated ROS generation. It was hypothesized that administering
      globular adiponectin (gAdp) via injectable biodegradable thermosensitive triblock
      copolymer might effectively reduce ROS generation in endothelial cells. In this
      study, gAdp was incorporated into and released from the polymer gel. The released
      gAdp was further investigated by comparing it with the intact gAdp with regard to
      the efficiency in reducing ROS and activating cAMP. The released gAdp effectively
      suppressed excess ROS production in the in vitro endothelial cell culture model
      under high-glucose condition via cAMP/PKA pathway. These data provide a rationale
      for developing controlled release dosage form of gAdp as a therapeutic tool for
      oxidative stress-related pathology in patients with diabetes.

PMID- 18619505
TI  - Kisspeptin and the seasonal control of reproduction in hamsters.
AB  - Reproduction is a complex and energy demanding function. When internal and
      external conditions might impair reproductive success (negative energy balance,
      stress, harsh season) reproductive activity has to be repressed. Recent evidence
      suggests that these inhibitory mechanisms operate on Kiss1-expressing neurons,
      which were recently shown to be implicated in the regulation of GnRH release.
      Hamsters are seasonal rodents which are sexually active in long photoperiod and
      quiescent in short photoperiod. The photoperiodic information is transmitted to
      the reproductive system by melatonin, a pineal hormone whose secretion is
      adjusted to night length. The photoperiodic variation in circulating melatonin
      has been shown to synchronize reproductive activity with seasons, but the
      mechanisms involved in this effect of melatonin were so far unknown. Recently we
      have observed that Kiss1 mRNA level in the arcuate nucleus of the Syrian hamster
      is lower in short photoperiod, when animals are sexually quiescent. Notably,
      intracerebroventricular infusion of Kiss1 gene product, kisspeptin, in hamsters
      kept in short photoperiod is able to override the inhibitory photoperiod and to
      reactivate sexual activity. The inhibition of Kiss1 expression in short
      photoperiod is driven by melatonin because pinealectomy prevents decrease in
      Kiss1 mRNA level in short photoperiod and melatonin injection in long photoperiod
      down regulates Kiss1 expression. Whether melatonin acts directly on arcuate Kiss1
      expressing neurons or mediates its action via interneurons is the subject of the
      current investigations.

PMID- 18619506
TI  - Postmenopausal increase in KiSS-1, GPR54, and luteinizing hormone releasing
      hormone (LHRH-1) mRNA in the basal hypothalamus of female rhesus monkeys.
AB  - The G-protein coupled receptor, GPR54, and its ligand, kisspeptin-54 (a KiSS-1
      derived peptide) have been reported to be important players in control of LHRH-1
      release. However, the role of the GPR54 signaling in primate reproductive
      senescence is still unclear. In the present study we investigated whether KiSS-1,
      GPR54, and LHRH-1 mRNA in the brain change after menopause in female rhesus
      monkeys using quantitative real-time PCR. Results indicate that KiSS-1, GPR54,
      and LHRH-1 mRNA levels in the medial basal hypothalamus (MBH) in postmenopausal
      females (28.3+/-1.1 years of age, n=5) were all significantly higher than that in
      eugonadal adult females (14.7+/-2.1 years of age, n=9), whereas KiSS-1, GPR54,
      and LHRH-1 mRNA levels in the preoptic area (POA) did not have any significant
      changes between the two age groups. To further determine the potential
      contribution by the absence of ovarian steroids, we compared the changes in KiSS
      1, GPR54, and LHRH-1 mRNA levels in young adult ovarian intact vs. young
      ovariectomized females. Results indicate that KiSS-1 and LHRH-1 mRNA levels in
      the MBH, not POA, in ovariectomized females were significantly higher than those
      in ovarian intact females, whereas GPR54 mRNA levels in ovariectomized females
      had a tendency to be elevated in the MBH, although the values were not quite
      statistically significant. Collectively, in the primate the reduction in the
      negative feedback control by ovarian steroids appears to be responsible for the
      aging changes in kisspeptin-GPR54 signaling and the elevated state of the LHRH-1
      neuronal system.

PMID- 18619507
TI  - Interleukin-12 improves cytotoxicity of natural killer cells via upregulated
      expression of NKG2D.
AB  - Natural killer (NK) cells are crucial components of the innate immune system,
      providing the first line of defense against infectious pathogens and tumors.
      Interleukin (IL)-12 is an interleukin produced primarily by antigen-presenting
      cells that play an essential role in the interaction between the innate and
      adaptive arms of immunity acting upon T and NK cells to generate cytotoxic
      lymphocytes. In the present study, we explored the effect of IL-12 upregulation
      on the NK receptor NKG2D and on the promotion of NK cell function. IL-12 enhanced
      the cytotoxicity of NK cells to different solid and hematological tumor cell
      lines and promoted interferon-gamma secretion by NK cells. The IL-12-induced
      cytolytic effect was dependent on the interaction of NKG2D with its ligand, MICA,
      because blockade of either protein attenuated the effect of IL-12 on NK
      cytolysis. Reverse transcriptase-polymerase chain reaction and fluorescence
      activated cell sorting analyses indicated that IL-12 treatment increased NKG2D
      transcripts and surface expression in NK cells. Also, IL-12 augmented the
      expression of cytotoxic effector molecules, TRAIL and perforin, and the
      phosphorylation of STAT1, STAT4, and ERK1/2, which may also contribute to lysis
      by NK cells. These results are encouraging for the potential use of IL-12 as part
      of immunotherapy.

PMID- 18619508
TI  - L-selectin ligation-induced CSF-1 gene transcription is regulated by AP-1 in a c
      Abl kinase-dependent manner.
AB  - L-selectin is a cell adhesion molecule that plays an important role both in
      mediating the initial capture and subsequent rolling of leukocytes along the
      endothelial cells and in the signal transduction for leukocyte activation. In our
      previous studies, we reported that L-selectin ligation could increase macrophage
      colony-stimulating factor (CSF)-1 gene transcription, in which c-Abl acts as a
      crucial cytoplasmic kinase. Here we investigated the function of the nuclear c
      Abl kinase in the CSF-1 gene transcriptional events triggered by L-selectin
      ligation. We determined that c-Abl kinase recruits to the nucleus following L
      selectin ligation, and the nuclear c-Abl kinase can phosphorylate c-Jun and
      regulate activator protein (AP)-1 activity. Furthermore, the activated c-Abl
      kinase interacts with AP-1 and forms a complex in the CSF-1 promoter region to
      regulate CSF-1 gene transcription in the L-selectin ligation-activated cells.
      These results indicate that nuclear c-Abl kinase can activate CSF-1 gene
      transcription by regulating AP-1 activity in the signaling events induced by L
      selectin ligation.

PMID- 18619510
TI  - Interpretation of results of the cost-effectiveness analysis reported by
      Pellissier et al. on October 2007.

PMID- 18619509
TI  - Application of quantitative gene expression analysis for pertussis vaccine safety
      control.
AB  - Although vaccines are routinely used to prevent infectious diseases, little is
      known about the comprehensive influences caused by vaccines. In this study, we
      showed, using comprehensive gene expression analysis, that pertussis vaccine
      affected many genes in multiple organs of vaccine-treated animals. In particular,
      lung was revealed to be the most suitable target to evaluate pertussis vaccine
      toxicity. The 13 genes identified from the analysis of vaccine-treated lung at
      day 1 showed a clear dendrogram corresponding to pertussis vaccine toxicity.
      Furthermore, quantitative analysis of these genes revealed a positive correlation
      between their respective expression levels and the degree of toxic effects
      observed in samples that had been treated with various doses of reference
      pertussis vaccines. The quantification of this 13 gene-set is an indicator of the
      vaccine toxicity-related reaction.

PMID- 18619511
TI  - 12-week clinical exposure evaluation of a third-generation electrically heated
      cigarette smoking system (EHCSS) in adult smokers.
AB  - This randomized, controlled, forced-switching, open-label, parallel-group, single
      center study in 90 male and female adult smokers evaluated six biomarkers of
      tobacco smoke exposure over a 12-week period of unrestricted smoking in the
      participants' normal life setting. Baseline biomarker levels were measured, then
      participants were randomly assigned to switch to an electrically heated cigarette
      smoking system (EHCSS, Series K) or to continue smoking a conventional cigarette
      (CC) of similar tar yield (Federal Trade Commission method) for 12 weeks.
      Compared to Baseline, adult smokers who switched to the EHCSS for 12 weeks in
      their normal life setting had significantly reduced nicotine equivalents (-33%),
      total NNAL (a biomarker for NNK, -63%), 1-OHP (a surrogate biomarker for
      polycyclic aromatic hydrocarbons, -38%), carboxyhemoglobin (a biomarker for
      carbon monoxide, -23%), 3-HPMA (a biomarker for acrolein, -25%) and S-PMA (a
      biomarker for benzene, -49%), whereas exposure was stable in the CC control
      group.

PMID- 18619512
TI  - Safety assessment of dietary diacylglycerol oil: a two-generation reproductive
      toxicity study in rats.
AB  - Diacylglycerol (DAG) oil is a novel edible oil with similar taste and usability
      characteristics as conventional edible oils. Recent studies suggest that DAG oil
      may be helpful in the prevention and management of obesity. The objective of the
      present two-generation study was to evaluate potential adverse effects of DAG oil
      on reproductive processes. DAG oil was administered via gavage to rats
      (30/sex/group) for at least 70 days prior to mating, at dose levels of 0, 1.25,
      2.5 or 5.0 ml/kg/day (0, 1160, 2320 and 4630 mg/kg/day). An additional group
      received a triacylglycerol (TAG) oil with a similar fatty acid composition to DAG
      oil. The rats were treated throughout the mating, gestation and lactation
      periods. Administration of DAG or TAG oil did not reveal any toxicologically
      significant effects on reproductive performance (mating, fertility and
      copulation/conception indices). DAG oil did not affect mean gestation lengths,
      the process of parturition, spermatogenic parameters, organ weights,
      histopathologic findings, mean numbers of pups born, implantation sites and
      unaccounted sites. F1 and F2 pup viability, live litter sizes, body weights, mean
      age of attainment of balanopreputial separation and vaginal patency were similar
      to those in the control group. Based on the results of this study, a dose level
      of 5.0 ml/kg (4630 mg/kg/day) was considered as the no-observed-adverse-effect
      level for reproductive and systemic toxicity, and neonatal toxicity.

PMID- 18619513
TI  - An immune network inspired evolutionary algorithm for the diagnosis of
      Parkinson's disease.
AB  - This paper presents a novel evolutionary algorithm inspired by protein/substrate
      binding exploited in enzyme genetic programming (EGP) and artificial immune
      networks. The immune network-inspired evolutionary algorithm has been developed
      in direct response to an application in clinical neurology, the diagnosis of
      Parkinson's disease. The inspiration for, and implementation of the algorithm is
      described and its performance to the application area considered.

PMID- 18619514
TI  - Caenorhabditis elegans body wall muscles are simple actuators.
AB  - Over the past four decades, one of the simplest nervous systems across the animal
      kingdom, that of the nematode worm Caenorhabditis elegans, has drawn increasing
      attention. This system is the subject of an intensive concerted effort to
      understand the behaviour of an entire living animal, from the bottom up and the
      top down. C. elegans locomotion, in particular, has been the subject of a number
      of models, but there is as yet no general agreement about the key (rhythm
      generating) elements. In this paper we investigate the role of one component of
      the locomotion subsystem, namely the body wall muscles, with a focus on the role
      of inter-muscular gap junctions. We construct a detailed electrophysiological
      model which suggests that these muscles function, to a first approximation, as
      mere actuators and have no obvious rhythm generating role. Furthermore, we show
      that within our model inter-muscular coupling is too weak to have a significant
      electrical effect. These results rule out muscles as key generators of
      locomotion, pointing instead to neural activity patterns. More specifically, the
      results imply that the reduced locomotion velocity observed in unc-9 mutants is
      likely to be due to reduced neuronal rather than inter-muscular coupling.

PMID- 18619515
TI  - Molecular biomarkers of endocrine disruption in small model fish.
AB  - A wide range of environmental contaminants can interfere with hormonal regulation
      in vertebrates. These endocrine disrupting chemicals (EDCs) are of high relevance
      for human and wildlife health, since endocrine signalling controls many essential
      physiological processes which impact on the individual's health, such as growth
      and development, stress response, and ultimately reproduction and population
      development. Small fish represent a cost-effective model for testing potential
      EDCs allowing the possibility to integrate from molecular to phenotypic and
      functional effects. We have comprehensively reviewed exposure-effect data from
      four different small model fish: zebrafish, medaka, fathead minnow, and the three
      spined stickleback. The majority of available data refer to EDCs interfering with
      reproductive hormones. However, we have also included interactions with other
      hormone systems, particularly the thyroid hormones. We demonstrate that the
      available data clearly indicates the predictive potential of molecular
      biomarkers, supporting the development and regulatory application of simple
      molecular-based screening assays using small model fish for EDC testing.

PMID- 18619516
TI  - The chicken embryo as a model for developmental endocrinology: development of the
      thyrotropic, corticotropic, and somatotropic axes.
AB  - The ease of in vivo experimental manipulation is one of the main factors that
      have made the chicken embryo an important animal model in developmental research,
      including developmental endocrinology. This review focuses on the development of
      the thyrotropic, corticotropic and somatotropic axes in the chicken, emphasizing
      the central role of the pituitary gland in these endocrine systems. Functional
      maturation of the endocrine axes entails the cellular differentiation and
      acquisition of cell function and responsiveness of the different glands involved,
      as well as the establishment of top-down and bottom-up anatomical and functional
      communication between the control levels. Extensive cross-talk between the above
      mentioned axes accounts for the marked endocrine changes observed during the last
      third of embryonic development. In a final paragraph we shortly discuss how
      genomic resources and new transgenesis techniques can increase the power of the
      chicken embryo model in developmental endocrinology research.

PMID- 18619517
TI  - Cell subpopulations of nicotine-sensitive subfornical organ neurons in rat.
AB  - The subfornical organ (SFO), which is related to drinking and cardiovascular
      regulation, is activated by central application of nicotine (NIC) and angiotensin
      II (ANG). However, NIC-induced drinking is much smaller than ANG-induced one
      although approximately 60% of SFO neurons are affected by both NIC and ANG.
      Therefore, some specific subpopulations of SFO neurons for NIC or ANG may be
      related to such different drinking responses. To clarify subpopulations of NIC
      sensitive neurons, electrophysiological properties of SFO neurons with the
      application of NIC was investigated at whole-cell patch-clamp recordings. Based
      on our developed electrophysiological criteria of the recovery kinetics of
      tetraethylammonium-resistant transient outward K(+) currents, two sub-types (F-
      and S-type neurons) were distinguished. Twenty-nine dissociated SFO neurons were
      examined to determine whether they showed NIC-induced inward currents. Most F
      type neurons (n=19/21) showed NIC sensitivity, but most S-type neurons (n=7/8)
      did not. Our previous study had demonstrated that half of the F-type and all of
      the S-type units showed ANG sensitivity. These suggests that almost all of the
      NIC-sensitive SFO neurons were electrophysiologically classified as the F-type,
      but not S-type, and this differs in part from angiotensin sensitivity. The
      different subpopulations for chemical sensitivities in the SFO may be related to
      different drinking responses.

PMID- 18619518
TI  - Dissociation of thermal hypoalgesia and epidermal denervation in streptozotocin
      diabetic mice.
AB  - The quantification of epidermal innervation, which consists primarily of heat
      sensitive C-fibers, is emerging as a tool for diagnosing and staging diabetic
      neuropathy. However, the relationship between changes in heat sensitivity and
      changes in epidermal innervation has not yet been adequately explored. Therefore,
      we assessed epidermal nerve fiber density and thermal withdrawal latency in the
      hind paw of Swiss Webster mice after 2 and 4 weeks of streptozotocin-induced
      diabetes. Thermal hypoalgesia developed after only 2 weeks of diabetes, but a
      measurable reduction in PGP9.5-immunoreactive epidermal nerve fiber density did
      not appear until 4 weeks. These data suggest that impaired epidermal nociceptor
      function contributes to early diabetes-induced thermal hypoalgesia prior to the
      loss of peripheral terminals.

PMID- 18619519
TI  - Error-related negativity varies with the activation of gender stereotypes.
AB  - The error-related negativity (ERN) was suggested to reflect the response
      performance monitoring process. The purpose of this study is to investigate how
      the activation of gender stereotypes influences the ERN. Twenty-eight male
      participants were asked to complete a tool or kitchenware identification task.
      The prime stimulus is a picture of a male or female face and the target stimulus
      is either a kitchen utensil or a hand tool. The ERN amplitude on male-kitchenware
      trials is significantly larger than that on female-kitchenware trials, which
      reveals the low-level, automatic activation of gender stereotypes. The ERN that
      was elicited in this task has two sources--operation errors and the conflict
      between the gender stereotype activation and the non-prejudice beliefs. And the
      gender stereotype activation may be the key factor leading to this difference of
      ERN. In other words, the stereotype activation in this experimental paradigm may
      be indexed by the ERN.

PMID- 18619520
TI  - EEG, ECG and oxygen concentration changes from sea level to a simulated altitude
      of 4000m and back to sea level.
AB  - In order to describe how high altitude affects the body during a one night stay
      at 4000m experiments were performed in a hypobaric chamber and compared to a
      study on Dachstein (mountain in Austria, 2700m). Ten subjects had to perform a
      reaction time task at different altitudes. The EEG and ECG were recorded
      simultaneously. Additionally, the oxygen saturation of the blood was measured at
      different altitudes and the subjects filled out a Lake Louise questionnaire that
      describes the degree of altitude mountain sickness (AMS). After elevation from
      134m to 4000m in the hypobaric chamber heart-rate increased from 68.9bpm to
      81.6bpm, RMSSD (root mean square of squared differences of adjacent heart beat
      intervals) decreased from 54.3ms to 33.3ms, the LF/HF ratio increased from 2.5 to
      3.9 and oxygen saturation decreased to 82.7% after 11h at 4000m altitude. The
      Lake Louise Score (LSS) reached 3.4 after one night at 4000m. EEG beta activity
      between 14Hz and 18Hz was attenuated at 4000m and also after return to 134m. The
      results indicate that the subjects were not able to adapt to 4000m within 12h in
      the hypobaric chamber. Even after 1h after the return to 134m all parameters are
      still affected from the night at 4000m altitude. ECG and EEG changes are in line
      with results obtained at 2700m height at Dachstein.

PMID- 18619521
TI  - Bcl-x(L) inhibits Bax-induced alterations in mitochondrial respiration and
      calcium release.
AB  - Apoptosis is a natural cell elimination process involved in a number of
      physiological and pathological events. This process can be regulated by members
      of the Bcl-2 family. Bax, a pro-apoptotic member of this family, accelerates cell
      death, while the pro-survival member, Bcl-x(L), can antagonize the pro-apoptotic
      function of Bax to promote cell survival. In the present study, we have evaluated
      the effect of Bcl-x(L) on Bax-induced alterations in mitochondrial respiration
      and calcium release. We found that in primary cultured astrocytes, recombinant
      Bcl-x(L) is able to antagonize Bax-induced decrease in mitochondrial respiration
      and increase in mitochondrial calcium release. In addition, we found that Bcl
      x(L) can lower the calcium store in the endoplasmic reticulum, thus limiting
      potential calcium flux induced by apoptosis. This regulation of calcium flux by
      Bcl-x(L) may represent an important mechanism by which this protein promotes cell
      survival.

PMID- 18619522
TI  - Iron in arterial plaque: modifiable risk factor for atherosclerosis.
AB  - It has been proposed that iron depletion protects against cardiovascular disease.
      There is increasing evidence that one mechanism for this protection may involve a
      reduction in iron levels within atherosclerotic plaque. Large increases in iron
      concentration are seen in human atherosclerotic lesions in comparison to levels
      in healthy arterial tissue. In animal models, depletion of lesion iron levels in
      vivo by phlebotomy, systemic iron chelation treatment or dietary iron restriction
      reduces lesion size and/or increases plaque stability. A number of factors
      associated with increased arterial disease or increased cardiovascular events is
      also associated with increased plaque iron. In rats, infusion of angiotensin II
      increases ferritin levels and arterial thickness which are reversed by treatment
      with the iron chelator deferoxamine. In humans, a polymorphism for haptoglobin
      associated with increased cardiovascular disease is also characterized by
      increased lesional iron. Heme oxygenase 1 (HO1) is an important component of the
      system for mobilization of iron from macrophages. Human HO1 promoter
      polymorphisms causing weaker upregulation of the enzyme are associated with
      increased cardiovascular disease and increased serum ferritin. Increased
      cardiovascular disease associated with inflammation may be in part caused by
      elevated hepcidin levels that promote retention of iron within plaque
      macrophages. Defective retention of iron within arterial macrophages in genetic
      hemochromatosis may explain why there is little evidence of increased
      atherosclerosis in this disorder despite systemic iron overload. The reviewed
      findings support the concept that arterial plaque iron is a modifiable risk
      factor for atherogenesis.

PMID- 18619523
TI  - Tempol diminishes cocaine-induced oxidative damage and attenuates the development
      and expression of behavioral sensitization.
AB  - A variety of mechanisms has been suggested for cocaine toxicity, including the
      possibility that cocaine induces an increase in oxidative stress (OS) due to
      excessive oxidation of dopamine (e.g. dopamine quinine), or by redox cycling of
      cocaine oxidized metabolites. However, the association between oxidative status
      in the brain and cocaine induced-behavior is poorly understood. Therefore, we
      examined the ability of the unique antioxidant tempol to attenuate cocaine
      induced oxidative damage and behavioral response. Acute cocaine treatment
      significantly elevated OS markers in prefrontal cortex (PFC) and nucleus
      accumbens (NAc) in rats, both in slices and following a single cocaine injection,
      which corresponded with a decrease in total antioxidant capacity (TAC). Tempol,
      at the optimal concentration we determined that was needed to observe an
      antioxidant non-toxic effect in vitro (1 mM) and in vivo (200 mg/kg), completely
      abolished the elevation of OS markers and prevented the reduction in TAC in these
      areas. Importantly, tempol injections, at a dose that does not affect the basal
      levels of locomotor activity, attenuated both the development and expression of
      cocaine-induced locomotor sensitization. Finally, in cocaine-sensitized animals,
      tempol prevented the elevation of OS markers in both PFC and NAc. Our findings
      suggest that oxidation of specific sites in the brain reward system by cocaine is
      accompanied with behavioral changes. Tempol has a neuro-protective effect against
      cocaine toxicity in these regions, and it may be beneficial in the treatment of
      cocaine addiction.

PMID- 18619524
TI  - Harms and benefits of lymphocyte subpopulations in patients with acute stroke.
AB  - Lymphocytes are major players in the development of innate and adaptive immune
      responses but their behavior in patients with acute stroke has received little
      attention. EXPERIMENTAL PROCEDURES: Using flow cytometry we identified total
      lymphocytes, T cells, helper T (Th) cells, cytotoxic T lymphocytes (CTL), natural
      killer (NK) cells, B cells, and regulatory T (Treg) cells in 46 consecutive
      patients with acute stroke within a median of 180 min of clinical onset, and at
      days 2, 7, and 90. Daily neurological score (National Institutes of Health Stroke
      Scale), diffusion-weighted imaging on brain magnetic resonance imaging,
      functional impairment, and stroke-associated infection (SAI) at day 7 were
      assessed. Apoptosis in lymphocyte subsets, tumor necrosis factor (TNF) 
      alpha/interleukin (IL) -4 production in stimulated Th and CTL, cluster of
      differentiation 86 (CD86) (B7-2) expression in B cells, cortisol and metanephrine
      in serum were measured. Multivariate analyses were used to evaluate SAI, and
      stroke outcome. RESULTS: Increased apoptosis and a fall of T, Th, CTL, B, and
      Treg cells were observed after stroke. Severer stroke on admission and SAI
      disclosed a greater decline of T, Th, and CTL cells. Increased cortisol and
      metanephrine was associated with severe stroke and SAI, and inversely correlated
      with T, and CTL. T cells, and CTL were correlated with infarct growth. Stroke but
      not SAI resulted in lower TNF-alpha production in Th cells. SAI showed the
      greatest fall of lymphocytes, T, Th, and CTL, but not B cells, or Treg. Poor
      outcome was associated with reduced levels of B cells, and increased expression
      of CD86 in B cells, but not with SAI. CONCLUSION: Lymphopenia and increased
      apoptosis of T, Th, CTL, Treg and B cells are early signatures after human
      stroke. A decreased cellular response after stroke is a marker of ongoing brain
      damage, the stress response, and a higher risk of infection. A lower humoral
      response is predictor of poorer long-term outcome.

PMID- 18619525
TI  - Subcellular localization of transporters along the rat blood-brain barrier and
      blood-cerebral-spinal fluid barrier by in vivo biotinylation.
AB  - Nutrient transporters and ABC efflux pumps at the blood-brain barrier are major
      determinants of drug penetration into the brain. Immunohistochemical analysis of
      transporter subcellular localization is challenging due to the close apposition
      of the luminal and abluminal microvessel plasma membranes. We employed in vivo
      perfusion of biotinylation reagent through rat brain microvessels to domain
      specifically label proteins exposed on the microvessel luminal surface. Using
      this approach, we analyzed the luminal/abluminal localization of a number of
      blood-brain barrier transporters identified by quantitative PCR profiling as
      being highly expressed and enriched in rat brain endothelial cells compared with
      whole brain. We also examined the apical/basal-lateral distribution of
      transporters in the choroid plexus, a secondary site for transport of nutrients
      between the blood and CNS. We detected P-glycoprotein (Pgp) (Abcb1), ATP-binding
      cassette (Abc) g2, multidrug resistance protein (Mrp) 4 (Abcc4), glucose
      transporter 1 (Glut1) (Slc2a1), Lat1 (Slc7a5), and monocarboxylate transporter-1
      (Mct1) (Slc16a1) on the luminal surface of rat cerebral microvessels by both
      immunofluorescence staining and Western blotting of in vivo biotinylated
      proteins. Mrp1 (Abcc1) appeared primarily abluminal by immunofluorescence
      staining, and was barely detectable in the biotinylated protein fraction. Organic
      anion transporter (Oat) 3 (Slc22a8), organic anion transporter polypeptide (Oatp)
      2b1 (Slco2b1, Oatpb), and Mrp5 (Abcc5) were not detected on the luminal surface
      using either method, while Oatp1a4 (Slco1a4, Oatp2) appeared to partially
      localize to the microvessel lumen by immunofluorescence staining, but was not
      detected in the biotinylated protein fraction by Western blotting. Lat1, Mrp1 and
      Mrp4 were detected on the basal-lateral surface of lateral ventricle choroid
      plexus epithelial cells. Mrp5, Oct3 and Oatp2b1 (Oatpb) were detected in the
      ependymal cells lining the ventricle. We did not detect Pgp expression in choroid
      plexus by immunofluorescence staining. In vivo biotinylation provides a method
      for domain-specific labeling of luminal surface proteins within the capillaries
      of the blood-brain barrier, allowing for biochemical analysis of protein
      localization and facilitating optical discrimination of the luminal and abluminal
      endothelial surfaces.

PMID- 18619526
TI  - Similarity and discrimination learning in humans.
AB  - In an experiment involving a new behavioural preparation the role played by
      similarity in discrimination learning was examined using visual patterns (i.e.,
      paintings) that might share common elements (specifically, A, BC, and ABC). A-C
      were small stars of three specific colours (target colours), which were
      intermixed with other stars of two different colours (distracting colours). The
      target colours were balanced through A-C. Students received discrimination
      training in which a fictitious painter was the author of paintings A and BC,
      while paintings ABC were assigned to a second fictitious painter. During
      training, the students had to make a choice, in the presence of each pattern,
      between two response keys, each of them indicating one of the painters. The time
      taken to respond was also measured. Feedback was always given after each key
      press. The results showed that while at times the A+ ABC- discrimination was
      acquired more readily than was the BC+ ABC- discrimination, on other occasions
      the reverse was also true, the critical factor being the way in which the colours
      were combined.

PMID- 18619527
TI  - Zebrafish U6 small nuclear RNA gene promoters contain a SPH element in an unusual
      location.
AB  - Promoters for vertebrate small nuclear RNA (snRNA) genes contain a relatively
      simple array of transcriptional control elements, divided into proximal and
      distal regions. Most of these genes are transcribed by RNA polymerase II (e.g.,
      U1, U2), whereas the U6 gene is transcribed by RNA polymerase III. Previously
      identified vertebrate U6 snRNA gene promoters consist of a proximal sequence
      element (PSE) and TATA element in the proximal region, plus a distal region with
      octamer (OCT) and SphI postoctamer homology (SPH) elements. We have found that
      zebrafish U6 snRNA promoters contain the SPH element in a novel proximal position
      immediately upstream of the TATA element. The zebrafish SPH element is recognized
      by SPH-binding factor/selenocysteine tRNA gene transcription activating
      factor/zinc finger protein 143 (SBF/Staf/ZNF143) in vitro. Furthermore, a
      zebrafish U6 promoter with a defective SPH element is inefficiently transcribed
      when injected into embryos.

PMID- 18619528
TI  - State of the art and perspectives for the delivery of antisense oligonucleotides
      and siRNA by polymeric nanocarriers.
AB  - Knocking down gene expression using either antisense oligonucleotides (AS-ODNs)
      or small interfering RNA (siRNAs) has raised a lot of interest in designing new
      pathways for therapeutics. Despite their potentialities, these negatively charged
      and hydrophilic molecules request chemical modifications or a carrier that allows
      cell recognition, cell internalization and moreover subcellular penetration.
      Although chemical modifications were brought to the basic AS-ODNs and siRNAs,
      their sensitivity to degradation and poor intracellular penetration is still
      hampering their clinical applications. We present here the potentialities of
      polymeric carriers or the use of alternative administration route such as oral,
      ocular and skin delivery to improve their delivery and to circumvent the hurdles
      for their clinical applications.

PMID- 18619529
TI  - Apoptosis/necrosis switch in two different cancer cell lines: influence of
      benzoquinone- and hydrogen peroxide-induced oxidative stress intensity, and
      glutathione.
AB  - Depending on the strength of oxidative stress, cells exhibit proliferative,
      apoptotic or necrotic responses. We have investigated whether the severity of
      glutathione (GSH) depletion could determine the type of cell death using 1,4
      benzoquinone (BQ) and H(2)O(2) in two different tumor cell lines (human mammary
      gland carcinoma MCF-7 and rat hepatoma H5-6). BQ-treated surviving cells showed
      an increase in GSH, but no detectable oxidized glutathione (GSSG) nor reactive
      oxygen species (ROS) augmentation. Alternatively, H(2)O(2) depressed GSH. BQ
      induced mostly apoptosis, up to 90% cell elimination, while necrosis was
      prominent in H(2)O(2)-treated cultures. The resistance of BQ-treated cells to
      necrosis could be due to increased cellular GSH and formation of BQ-GSH
      conjugates which are less toxic than free BQ, minimal toxicity being provided by
      GS4-BHQ. This ability of certain cancer cells to tightly keep the apoptotic
      pathway may have therapeutic applications for oxidation-based drugs.

PMID- 18619530
TI  - Mitochondria and ubiquitin-proteasomal system interplay: relevance to Parkinson's
      disease.
AB  - The cellular mechanisms that may underlie the death of dopaminergic neurons in
      Parkinson's disease are ubiquitin-proteasomal system (UPS) impairment,
      mitochondrial dysfunction, and oxidative stress. The goal of this work was to
      elucidate the correlation between mitochondrial dysfunction and UPS impairment,
      focusing on the role of oxidative stress. Our data revealed that mitochondria-DNA
      depleted cells (rho0) are compromised at the mitochondrial and UPS levels and
      also show an alteration of the oxidative status. In parental cells (rho+), MPP(+)
      induced a clear inhibition of complex I activity, as well as an increase in
      ubiquitinylated protein levels, which was not observed in cells treated with
      lactacystin. Moreover, MPP(+) induced a decreased in the 20S chymotrypsin-like
      and peptidyl-glutamyl peptide hydrolytic-like proteolytic activities after 24 h
      of exposure. ROS production was increased in rho+ cells treated with MPP(+) or
      lactacystin, at early treatment periods. MPP(+) induced an increase in carbonyl
      group formation in rho+ cells. The results suggest that a mitochondrial
      alteration leads to an imbalance in the cellular oxidative status, inducing a
      proteasomal deregulation, which may exacerbate protein aggregation, and
      consequently degenerative events.

PMID- 18619531
TI  - Identification of phosphorylation sites on transcription factor Sp1 in response
      to DNA damage and its accumulation at damaged sites.
AB  - DNA damage induces hyper-phosphorylation of the Sp1 transcriptional factor. We
      have demonstrated that ionizing radiation-associated DNA double-strand breaks
      (DSBs) induce phosphorylation of at least Ser-56 and Ser-101 residues on Sp1 in
      an ATM-dependent manner. UV irradiation- or hydroxyurea (HU)-induced replicative
      stress results in phosphorylation of only the Ser-101 residue. Furthermore,
      silencing of the ATM- and Rad3-related protein (ATR) in ATM-deficient cells
      treated with HU abrogated the Ser-101 phosphorylation. Thus, phosphorylation of
      Ser-101 on Sp1 appears to be a general response to DNA damage dependent on both
      ATM and ATR. Although silencing of Sp1 expression by siRNA targeting resulted in
      an increase in sensitivity to ionizing radiation (IR), the Ser-101
      phosphorylation did not affect transcriptional activity from the Sp1 responsive
      promoter. Confocal laser microscopy analysis revealed co-localization of
      phosphorylated Sp1 at Ser-101 with phosphorylated ATM at Ser-1981, the affected
      sites representing DSBs. These observations suggest that phosphorylated Sp1 might
      play a role in DNA repair at damage sites rather than functioning in
      transcriptional regulation.

PMID- 18619532
TI  - Surface-bound proteins of Lactobacillus plantarum 423 that contribute to adhesion
      of Caco-2 cells and their role in competitive exclusion and displacement of
      Clostridium sporogenes and Enterococcus faecalis.
AB  - Elongation factor Tu (EF-Tu), glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      and triosephosphate isomerase (TPI) are surface-bound proteins with a role in
      adhesion of Lactobacillus plantarum 423 to Caco-2 cells. Removal of surface-bound
      proteins from L. plantarum 423 (treated with 4M guanidine-HCl) reduced adhesion
      to Caco-2 cells by 40%. In a competitive exclusion experiment where all three
      strains were given an equal chance to adhere to Caco-2 cells, L. plantarum 423
      prevented 71% of cells of Clostridium sporogenes LMG 13570 and 89% of cells of
      Enterococcus faecalis LMG 13566 from adhering. Cells of L. plantarum 423, from
      which surface-bound proteins were removed, prevented 49% of cells of C.
      sporogenes LMG 13570 and 70% of cells of E. faecalis LMG 13566 from adhering to
      Caco-2 cells, suggesting that factors other than surface-bound proteins are
      involved in adhesion. Colonization of L. plantarum 423 to Caco-2 cells prevented
      adhesion of 74% of cells of C. sporogenes LMG 13570 and 62% of cells of E.
      faecalis LMG 13566. Furthermore, L. plantarum 423 displaced 81% of cells of C.
      sporogenes LMG 13570 and 91% of cells of E. faecalis LMG 13566 from Caco-2 cells.
      L. plantarum 423 is a potential probiotic strain.

PMID- 18619533
TI  - The ubiquitin-proteasome system in colorectal cancer.
AB  - The proteasome is a multiprotein complex that regulates the stability of hundreds
      of cellular proteins and thus, it is implicated in virtually all cellular
      functions. Most of the time, to be recognized and processed by the proteasome, a
      protein has to be linked to a chain of ubiquitin molecules. Cell proliferation,
      apoptosis, angiogenesis and motility, processes with particular importance for
      carcinogenesis are regulated by the ubiquitin-proteasome system (UPS). In
      colorectal epithelium, UPS plays a role in the regulation of the Wnt/beta
      catenin/APC/TCF4 signaling which regulates proliferation of colorectal epithelial
      cells in the bottom of the crypts and the inhibition of this proliferation as
      cells move towards colon villi tips. In most colorectal cancers APC (Adenomatous
      Polyposis Coli) disabling mutations interfere with the ability of the proteasome
      to degrade beta-catenin leading to uninhibited cell proliferation. Other key
      molecules in colorectal carcinogenesis such as p53, Smad4 and components of the k
      ras pathways are also regulated by the UPS. In this review I discuss the role of
      UPS in colorectal carcinogenesis and colorectal cancer prognosis and aspects of
      its inhibition for therapeutic purposes.

PMID- 18619534
TI  - Differential scanning calorimetry study on drug release from an inulin-based
      hydrogel and its interaction with a biomembrane model: pH and loading effect.
AB  - Inulin has been derivatized with methacrylic anhydride (MA) and succinic
      anhydride (SA) to obtain a methacrylated/succinilated derivative (INU-MA-SA) able
      to produce a pH sensitive hydrogel after UV irradiation. The hydrogel was
      characterized and loaded with diflunisal (10.4, 17 and 24%, w/w) chosen as a
      model drug. The drug release from INU-MA-SA-based hydrogel to a biomembrane model
      made by unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) was
      investigated at pH 4.0 and 7.4 by differential scanning calorimetry (DSC) that
      appears to be a suitable technique to follow the transfer kinetics of a drug from
      a controlled release system to a biomembrane model. The drug release from the
      hydrogel was compared with the dissolution of drug solid form by examining the
      effects exerted on the thermotropic behaviour of the DMPC unilamellar vesicles.
      The transferred drug and the release rate were affected by the drug loading as
      well as by the pH of the external medium. In particular the release was not
      linearly related to the drug loading but an intermediate loading allowed a better
      release at both investigated pHs, with a faster and more complete release
      observed at pH 7.4.

PMID- 18619535
TI  - Evaluation of the binding effect of human serum albumin on the properties of
      granules.
AB  - The main objective of this study was the application of a solution of human serum
      albumin as a granulating fluid. The properties of the granules formed were
      evaluated and compared with those when a conventional binder was applied in the
      same concentration. The powder mixture contained a soluble (mannitol) and an
      insoluble component (different types of cellulose). The protein solution applied
      exerted an appropriate aggregating effect if the system contained
      microcrystalline celluloses. Powdered cellulose was not suitable for the
      granulation with human serum albumin solution. As compared with the same
      concentration of the conventionally applied cellulose ethers as binder, the
      prepared granules exhibited a larger particle size, a significantly better
      compressibility, a higher breaking hardness and a favourable deformation process.
      These findings mainly reflect the good adhesive properties of the protein. The
      best compressibility and mechanical behaviour were attained on the application of
      the microcrystalline cellulose Vivapur type 105. This favourable behaviour may be
      connected with the wettability of cellulose. These results suggest that the
      formulation of tablets may be easier from an active agent in the serum that binds
      to albumin (e.g. interferon) since the amount of additives (binder) can be
      reduced.

PMID- 18619536
TI  - Adsorption of pharmaceutical excipients onto microcrystals of siramesine
      hydrochloride: effects on physicochemical properties.
AB  - A common challenge in the development of new drug substances is poor dissolution
      characteristics caused by low aqueous solubility. In this study, microcrystals
      with optimized physicochemical properties were prepared by precipitation in the
      presence of excipients, which adsorbed to the particle surface and altered
      particle size, morphology, and dissolution rate. The poorly water-soluble drug
      siramesine hydrochloride was precipitated by the antisolvent method in the
      presence of each of various polymeric and surface active excipients. Powder
      dissolution studies of six of the resulting particle systems showed a significant
      increase in percent dissolved after 15 min compared to the starting material. A
      quantitative determination of the amount of excipient adsorbed to the surface of
      the drug particles proved that only a very small amount of excipient was needed
      to exert a marked effect on particle properties. The adsorbed amount of excipient
      constituted less than 1.4% (w/w) of the total particle weight, and thus powders
      of very high drug loads were obtained. Sodium lauryl sulphate (SLS),
      hydroxypropyl methylcellulose (HPMC), and hydroxypropyl cellulose (HPC), which
      exhibited the greatest degree of adsorption, also had the greatest effect on the
      physicochemical properties of the particles. X-ray Photoelectron Spectroscopy
      (XPS) analysis of the surface composition and scanning electron microscopy
      studies on particle morphology suggested that the excipients adsorbed to specific
      faces of the crystals.

PMID- 18619537
TI  - Role for beta1 integrins in cortical osteocytes during acute musculoskeletal
      disuse.
AB  - The mammalian skeleton adjusts bone structure and strength in response to changes
      in mechanical loading, however the molecular and cellular mechanisms governing
      this process in vivo are unknown. Terminally differentiated osteoblasts, the
      osteocytes, are presumptive mechanosensory cells for bone, and cell culture
      studies demonstrate that beta1 integrins participate in mechanical signaling. To
      determine the role of beta1 integrins in osteoblasts in vivo, we used the Cre-lox
      system to delete beta1 integrin from cells committed to the osteoblast lineage.
      While pCol2.3 Cre-mediated recombination was widespread in bones from
      Colalpha1(I)-Cre+/beta1fl/fl conditional knockout mice (cKO), beta1 integrin
      protein was depleted from cortical osteocytes, but not from cancellous osteocytes
      or cells lining bone surfaces in adults. Bones from cKO mice that were normally
      loaded were similar in structure to WT littermates. However, hindlimb unloading
      of adult cKO mice for one week intended to cause bone loss (disuse osteopenia),
      resulted in unexpected, rapid changes in the geometry of cortical bone; hindlimb
      unloading increased the cross-sectional area, marrow area, and moments of inertia
      in cKO, but not WT mice. Furthermore, these hindlimb unloading-induced geometric
      changes in cortical bone of cKO mice resulted in increased whole bone bending
      stiffness and strength of the femur. Together, these results confirmed the
      concept that osteocytes are mechanosensory cells and showed beta1 integrins in
      cortical osteocytes limited changes in cortical geometry in response to disuse,
      thus providing the first in vivo evidence that beta1 integrins on osteocytes
      mediate specific aspects of mechanotransduction.

PMID- 18619538
TI  - Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods
      of anti-antibody measurement.
AB  - To date, millions of people have been treated with therapeutic monoclonal
      antibodies (TmAbs) for various indications. It is becoming increasingly clear
      that TmAbs can be immunogenic, which may reduce efficacy or induce adverse
      effects. Over the years, the importance of antibody formation has been questioned
      and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were
      reported. However, the methods to detect and quantify such antibodies used in the
      past have been problematic. Only recently, methods have been developed that have
      adequate sensitivity and are not seriously disturbed by false-positive reactions
      caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or
      Fc interactions of IgG4. The large number of treated patients, in combination
      with these new assays, presents a unique opportunity to study the anti-antibody
      immune response in man, possibly allowing us to manipulate immunogenicity in the
      future.

PMID- 18619540
TI  - Two-hybrid technologies in proteomics research.
AB  - Given that protein-protein interactions (PPIs) regulate nearly every living
      process; the exploration of global and pathway-specific protein interaction
      networks is expected to have major implications in the understanding of diseases
      and for drug discovery. Consequently, the development and application of
      methodologies that address physical associations among proteins is of major
      importance in today's proteomics research. The most widely and successfully used
      methodology to assess PPIs is the yeast two-hybrid system (YTH). Here we present
      an overview on the current applications of YTH and variant technologies in yeast
      and mammalian systems. Two-hybrid-based methods will not only continue to have a
      dominant role in the assessment of protein interactomes but will also become
      important in the development of novel compounds that target protein interaction
      interfaces for therapeutic intervention.

PMID- 18619541
TI  - Quantitative phosphoproteomic analysis of signaling network dynamics.
AB  - Protein phosphorylation mediated cellular signaling is a highly regulated,
      dynamic process that controls many aspects of cellular biology. Over the past few
      years many methods have been developed to quantify temporal dynamics of protein
      phosphorylation, including mass spectrometry, which can be applied in both an
      unbiased, discovery mode and in a targeted mode to monitor specific
      phosphorylation sites. Other methods, such as kinase activity assays and antibody
      microarrays, have been applied to quantify central nodes in the signaling
      network, yielding intriguing biological insights. This review provides a concise
      overview of the latest advances in the quantitative analysis of signaling
      dynamics including a brief commentary on the future of the field.

PMID- 18619539
TI  - Cadherins and mechanotransduction by hair cells.
AB  - Mechanotransduction, the conversion of a mechanical stimulus into an electrical
      signal is crucial for our ability to hear and to maintain balance. Recent
      findings indicate that two members of the cadherin superfamily are components of
      the mechanotransduction machinery in sensory hair cells of the vertebrate inner
      ear. These studies show that cadherin 23 (CDH23) and protocadherin 15 (PCDH15)
      form several of the extracellular filaments that connect the stereocilia and
      kinocilium of a hair cell into a bundle. One of these filaments is the tip link
      that has been proposed to gate the mechanotransduction channel in hair cells. The
      extracellular domains of CDH23 and PCDH15 differ in their structure from
      classical cadherins and their cytoplasmic domains bind to distinct effectors,
      suggesting that evolutionary pressures have shaped the two cadherins for their
      function in mechanotransduction.

PMID- 18619542
TI  - An investigation into CAG repeat length variation and N/C terminal interactions
      in the T877A mutant androgen receptor found in prostate cancer.
AB  - Prostate cancer may progress by circumventing ablation therapy due to mutations
      in the androgen receptor (AR) gene. The most intensively studied is the T877A
      mutation in the ligand binding domain (LBD), which causes the AR to become
      promiscuous, i.e., respond to a number of different ligands. Our investigations
      have shown that the T877A mutation alters the inverse relationship between CAG
      repeat length and transactivation in a noticeable albeit minor manner, while
      increasing N/C terminal interactions. In the presence of beta-catenin, a
      coactivator over-expressed in prostate cancer, the inverse relationship between
      CAG repeat length and transactivation is reversed for the wild type (wt) AR as
      well. We have also used molecular modeling with the AR and FXXLF and LXXLL
      peptides to investigate N/C terminal and coactivator interactions. In T877A, this
      approach revealed an increase in the flexibility of amino acid residues in the
      activation function 2 (AF-2) domain in the LBD, and a larger solvent accessible
      surface in T877A compared to the wt AR AF-2 domain. Thus, the improved induced
      fit of the AR N-terminal domain FXXLF-containing peptide into the T877A LBD could
      be due to the increased flexibility and solvent accessibility of the AF-2 domain.
      These new observations suggest that the AR CAG effect can be overridden by
      prostate cancer mutations, and also further our understanding of hormone
      refractory prostate cancer by helping to explain the promiscuity of the T877A
      mutation.

PMID- 18619543
TI  - Estrogen and progesterone regulate the IL-6 signal transduction pathway in
      antibody secreting cells.
AB  - Regulation of the immune response is necessary to allow successful pregnancy.
      Asymmetric IgG antibodies are involved in fetal maintenance. We have previously
      demonstrated that estrogen (E2) and progesterone (P4) modulate the synthesis of
      asymmetric antibodies but the underlying mechanisms remain unclear. Since IL-6
      and a progesterone-induced blocking factor (PIBF) were shown to regulate
      asymmetric antibody synthesis, in this work we analyzed whether E2 and P4 were
      able to modulate IL-6 signal transduction pathways and the ability of P4 to
      induce PIBF synthesis, in hybridoma B cells was also evaluated. We found that the
      IL-6 treatment induced an increase in the expression of gp130 and JAK1 by the
      hybridoma. E2 and P4 diminished the IL-6-induced gp130 expression in a dose
      dependent manner, whereas the expression of JAK1 was not significantly affected.
      At 10(-6)M concentration, the steroids inhibited the phosphorylation of gp130 and
      diminished the IL-6-induced STAT3 phosphorylation and translocation to the
      nucleus. Maximal PIBF expression was observed when the hybridoma was cultured
      with 10(-10)M P4, compared to the control (p<0.05). Results demonstrate two
      molecular mechanisms, the modulation of the IL-6R signal transduction pathway and
      PIBF induction, which could be involved in the immunoregulatory role of sexual
      steroids during pregnancy.

PMID- 18619544
TI  - C. sinensis ablates allograft vasculopathy when used as an adjuvant therapy with
      cyclosporin A.
AB  - Immunosuppressive treatments are available to suppress acute cardiac rejection;
      however, no viable treatment exists for long-term cardiac graft failure.
      Moreover, extended use of calcineurin inhibitor immunosuppressants, the mainstay
      of the current therapeutic for cardiac transplantation, leads to significant
      associated pathologies such as nephrotoxicity and increased risk of cardiac
      disease. For the last ten years alternatives to calcineurin inhibitors, or
      adjuvant therapies designed to complement their activities, have been explored.
      In tandem with this development, there has been considerable interest in
      Traditional Chinese Medicines (TCM) as sources for novel therapeutics. Our study
      examines the ability of the TCM Cordyceps sinensis to reduce acute and chronic
      rejection associated with cardiac transplantation. The objectives of this study
      were to first determine if oral delivery of the extract could reduce acute
      rejection in a rat heterotopic heart model of transplantation. The second
      objective was to determine, in vitro, if a sterile, aqueous extract of C.
      sinensis could decrease CD8+ T cell activity. The third objective was to
      determine if oral delivery of the extract could ablate allograft vasculopathy in
      a mouse abdominal aortic transplant model. We found that oral delivery of the
      extract demonstrated a reduction in acute rejection when used in conjunction with
      a sub-therapeutic dose of Cyclosporine. Further, we found, using a mixed
      lymphocyte reaction, that the extract was able to significantly reduce CD8+ T
      cell activity. Finally, we demonstrate that oral delivery of the extract, used
      with a therapeutic dose of Cyclosporine to suppress acute rejection, ablates
      allograft vasculopathy.

PMID- 18619545
TI  - Functional interference between glycogen synthase kinase-3 beta and the
      transcription factor Nrf2 in protection against kainate-induced hippocampal cell
      death.
AB  - Excitotoxicity mediated by glutamate receptors may underlay the pathology of
      several neurologic diseases. Considering that oxidative stress is central to
      excitotoxic damage, in this study we sought to analyze if the transcription
      factor Nrf2, guardian of redox homeostasis, might be targeted to prevent kainate
      induced neuron death. Hippocampal slices from Nrf2 knockout mice exhibited
      increased oxidative stress and cell death compared to those of control mice in
      response to kainate, as determined with the redox sensitive probes 2,7
      dichlorodihydrofluorescein diacetate (H(2)DCFAC) and propidium iodide and lactate
      dehydrogenase release, respectively, therefore demonstrating a role of Nrf2 in
      antioxidant protection against excitotoxicity. In the hippocampus of mice
      intraperitoneally injected with kainate we observed a rapid activation of Akt,
      inhibition of GSK-3beta and translocation of Nrf2 to the nucleus, but after 4 h
      Akt was inactive, GSK-3beta was active and Nrf2 was mostly cytosolic, therefore
      extending our previous studies which indicate that GSK-3beta excludes Nrf2 from
      the nucleus. Lithium, a GSK-3beta inhibitor, promoted Nrf2 transcriptional
      activity towards an Antioxidant-Response-Element (ARE) luciferase reporter and
      cooperated with sulforaphane (SFN) to induce this reporter and to increase the
      protein levels of heme oxygenase-1 (HO-1), coded by a representative ARE
      containing gene. Conversely, ARE activation by SFN was attenuated by over
      expression of active GSK-3beta. Finally, combined treatment with SFN and lithium
      attenuated oxidative stress and cell death in kainate-treated hippocampal slices
      of wild type mice but not Nrf2 null littermates. Our findings identify the axis
      GSK-3beta/Nrf2 as a pharmacological target in prevention of excitotoxic neuronal
      death.

PMID- 18619546
TI  - Bimolecular fluorescence complementation in structural biology.
AB  - Bimolecular fluorescence complementation is a method of probing protein-ligand
      interactions under physiological conditions. It provides a state-of-the-art tool
      to examine interactions observed in 3D structures of multi-component protein
      complexes, either to validate new experimental structures or to assess the
      correctness of homology models. Applications of the method range from homo- and
      hetero-oligomeric assemblies, including non-protein-ligands. Proof-of-principle
      experiments have also shown the potential of bimolecular fluorescence
      complementation to monitor protein complexes in a conformation-dependent manner.
      Here, recent highlights of structure-based applications of the method are
      outlined and assessed in terms of project-specific findings. These examples
      demonstrate the power of bimolecular fluorescence complementation to become a
      leading analysis tool in structural biology, to independently evaluate and
      characterize higher-order protein complexes.

PMID- 18619547
TI  - Particle-verification for single-particle, reference-based reconstruction using
      multivariate data analysis and classification.
AB  - As collection of electron microscopy data for single-particle reconstruction
      becomes more efficient, due to electronic image capture, one of the principal
      limiting steps in a reconstruction remains particle-verification, which is
      especially costly in terms of user input. Recently, some algorithms have been
      developed to window particles automatically, but the resulting particle sets
      typically need to be verified manually. Here we describe a procedure to speed up
      verification of windowed particles using multivariate data analysis and
      classification. In this procedure, the particle set is subjected to multi
      reference alignment before the verification. The aligned particles are first
      binned according to orientation and are binned further by K-means classification.
      Rather than selection of particles individually, an entire class of particles can
      be selected, with an option to remove outliers. Since particles in the same class
      present the same view, distinction between good and bad images becomes more
      straightforward. We have also developed a graphical interface, written in
      Python/Tkinter, to facilitate this implementation of particle-verification. For
      the demonstration of the particle-verification scheme presented here, electron
      micrographs of ribosomes are used.

PMID- 18619548
TI  - Probabilistic fibre tracking: differentiation of connections from chance events.
AB  - Probabilistic tractography methods that use Monte Carlo sampling of voxelwise
      fibre orientation probability density functions suffer from distance-related
      artefacts due to the propagation of uncertainty along the tract path. These are
      manifested as a preferential weighting of regions close to the tracking start
      point at the expense of more distant regions--an effect that can mask genuine
      anatomical connections. We propose a methodology based on comparison of the
      conventional connection probability map with a null connection map that defines
      the distribution of connections expected by a random tracking process and that is
      dominated by the same distance effects. When the connection probability is
      significantly greater than the result of the null tracking result this identifies
      voxels where the diffusion information is providing more evidence of connection
      than that expected from random tracking. We show that the null connection
      probability map used is governed by Poisson statistics within each voxel,
      allowing analytical estimation of connection values that are significantly
      different to the null connection values. The resultant significant connection
      maps can be combined with the conventional probabilistic tractography output to
      produce maps of significant connections which reduce distance-related artefacts
      by removing areas where the observed frequency of connection is dominated simply
      by distance effects and not the diffusion information. This is achieved by
      applying an objective statistical interpretation of observed patterns of
      connection which cannot be achieved by simple thresholding of conventional
      probabilistic tractography maps due to the distance effect.

PMID- 18619549
TI  - Phylogenetic and biogeographic complexity of Magnoliaceae in the Northern
      Hemisphere inferred from three nuclear data sets.
AB  - This study employs three nuclear genes (PHYA, LFY, and GAI1) to reconstruct the
      phylogenetic and biogeographic history of Magnoliaceae. A total of 104 samples
      representing 86 taxa from all sections and most subsections were sequenced.
      Twelve major groups are well supported to be monophyletic within Magnoliaceae and
      these groups are largely consistent with the recent taxonomic revision at the
      sectional and subsectional levels. However, relationships at deeper nodes of the
      subfamily Magnolioideae remain not well resolved. A relaxed clock relying on
      uncorrelated rates suggests that the complicated divergent evolution of
      Magnolioideae began around the early Eocene (54.57mya), concordant with
      paleoclimatic and fossil evidence. Intercontinental disjunctions of Magnoliaceae
      in the Northern Hemisphere appear to have originated during at least two geologic
      periods. Some occurred after the middle Miocene, represented by two well
      recognized temperate lineages disjunct between eastern Asia and eastern North
      America. The others may have occurred no later than the Oligocene, with ancient
      separations between or within tropical and temperate lineages.

PMID- 18619550
TI  - The immediate effect of nitric oxide on the rabbit bladder after ovariectomy.
AB  - Ovariectomy resulted in decreased blood flow and hypoxia to the bladder mucosa
      and smooth muscle. Nitric oxide (NO) played an important role in regulating
      bladder function during bladder ischemia and reperfusion. This study was designed
      to evaluate the role of NO on bladder function in the first few days after
      ovariectomy. Female rabbits were separated into three groups, one which received
      no medication, premedicated with N(omega)-nitro-L-arginine methyl ester (L-NAME)
      and the third treated with L-arginine. Non-ovariectomized controls and at 1 and 3
      days post-ovariectomy, animals from each group were euthanized. Cystometry and in
      vitro isometric contractile responses were recorded and the oxidative stress
      markers, nitrotyrosine and protein carbonylation were determined. L-NAME
      treatment did not significantly alter bladder function after ovariectomy. L
      Arginine fed, ovariectomized rabbits had lower intravesical pressure and better
      contractile responses to all forms of stimulation than the ovariectomized rabbits
      with or without L-NAME. Furthermore, the ovariectomized ones with or without L
      NAME had higher oxidative stress markers than L-arginine fed rabbits. This study
      clearly demonstrates that feeding rabbits with L-arginine can protect the bladder
      from oxidative free radical damage following short-term ovariectomy.

PMID- 18619551
TI  - Gene expression and morphological localization of NHE3, NCC and NKCC1a in
      branchial mitochondria-rich cells of Mozambique tilapia (Oreochromis mossambicus)
      acclimated to a wide range of salinities.
AB  - We explored molecular and morphological alteration in gill mitochondria-rich (MR)
      cells of Mozambique tilapia, Oreochromis mossambicus, acclimated to deionized
      freshwater (DFW), freshwater (FW), 1/3-diluted seawater (1/3 SW) and seawater
      (SW). Scanning electron microscopic observations revealed that the apical
      membrane of MR cells appeared as a flat or slightly projecting disk in DFW and
      FW, being larger in DFW than in FW. In contrast, the apical membrane typically
      formed a pit structure in 1/3 SW and SW. The mRNA expression levels of Na(+)/H(+)
      exchanger-3 (NHE3) and Na(+)/Cl(-) cotransporter (NCC) in the gills were
      increased with decreasing environmental salinity, whereas Na(+)/K(+)/2Cl(-)
      cotransporter-1a (NKCC1a) expression was upregulated by increasing salinity.
      Immunofluorescence staining showed that the MR cell population of DFW- and FW
      acclimated tilapia consisted mostly of MR cells with apical NHE3 and those with
      apical-NCC; MR cells with basolateral NKCC1a dominated in SW-acclimated tilapia.
      These results indicated that apical-NHE3 and apical-NCC MR cells were ion
      absorbing cells, and that basolateral-NKCC1a MR cells were ion-secreting cells.
      In fish acclimated to 1/3 SW, both ion-absorbing and secreting cells existed in
      the gills, suggesting that fish in near-isotonic water were equipped with
      mechanisms of both hyper- and hypoosmoregulation to prepare for environmental
      salinity changes.

PMID- 18619552
TI  - Effect of various factors on Pelagia noctiluca (Cnidaria, Scyphozoa) crude venom
      induced haemolysis.
AB  - The haemolytic power of isolated nematocysts from the scyphozoan Pelagia
      noctiluca was studied with attention to the effect of osmotic protectants as
      carbohydrates at different MW, cations as Mg2+, Ca2+, Ba2+,Cu2+, K+; proteases as
      collagenase, trypsin, alpha-chymotrypsin, papain; and antioxidants. Crude venom
      was at first obtained by sonication of holotrichous-isorhiza nematocysts
      previously isolated from oral arms of P. noctiluca and then haemolytically tested
      upon human erythrocytes. Osmotic protectants were effective in inhibiting the
      haemolytic power depending on their molecular weight so that total inhibition of
      crude venom-induced haemolysis was observed after PEG treatment
      (polyethyleneglycol 6000Da). Amongst divalent cations only Ba2+ and Cu2+
      significantly inhibited the haemolytic power of crude venom. Proteases seem not
      to alter the haemolytic activity while antioxidant compounds only slightly
      reduced the haemolytic power. Such findings may suggest a pore-forming mechanism
      for P. noctiluca crude venom rather than an oxidative damage to the cell
      membrane.

PMID- 18619553
TI  - Lipocalin-type prostaglandin D(2) synthase stimulates glucose transport via
      enhanced GLUT4 translocation.
AB  - Previously, we demonstrated that lipocalin-type prostaglandin D(2) synthase (L
      PGDS) knockout mice become glucose intolerant and display signs of diabetic
      nephropathy and accelerated atherosclerosis. In the current study we sought to
      explain the link between L-PGDS and glucose tolerance. Using the insulin
      sensitive rat skeletal muscle cell line, L6, we showed that L-PGDS could
      stimulate glucose transport approximately 2-fold as well as enhance insulin
      stimulated glucose transport, as measured by 2-deoxy-[(3)H]-glucose uptake. The
      increased glucose transport was not attributed to increased GLUT4 production but
      rather the stimulation of GLUT4 translocation to the plasma membrane, a
      phenomenon that was lost when cells were cultured under hyperglycemic (20 mM)
      conditions or pretreated with wortmannin. There was however, an increase in GLUT1
      expression as well as a 3-fold increase in hexokinase III expression, which was
      increased to nearly 5-fold in the presence of insulin, in response to L-PGDS at
      20 mM glucose. In addition, adipocytes isolated from L-PGDS knockout mice were
      significantly less sensitive to insulin-stimulated glucose transport than wild
      type. We conclude that L-PGDS, via production of prostaglandin D(2), is an
      important mediator of muscle and adipose glucose transport which is modulated by
      glycemic conditions and plays a significant role in the glucose intolerance
      associated with type 2 diabetes.

PMID- 18619554
TI  - Changes in bone morphogenetic protein receptor-IB localisation regulate
      osteogenic responses of human bone cells to bone morphogenetic protein-2.
AB  - Cell responses to bone morphogenetic proteins (BMP) depend on the expression and
      surface localisation of transmembrane receptors BMPR-IA, -IB and -II. The present
      study shows that all three antigens are readily detected in human bone cells.
      However, only BMPR-II was found primarily at the plasma membrane, whereas BMPR-IA
      was expressed equally in the cytoplasm and at the cell surface. Notably, BMPR-IB
      was mainly intracellular, where it was associated with a number of cytoplasmic
      structures and possibly the nucleus. Treatment with transforming growth factor
      beta1 (TGF-beta1) caused rapid translocation of BMPR-IB to the cell surface,
      mediated via the p38 mitogen-activated protein kinase (MAPK) and protein kinase C
      (PKC) pathways. The TGF-beta1-induced increase in surface BMPR-IB resulted in
      significantly elevated BMP-2 binding and Smad1/5/8 phosphorylation, although the
      receptor was subsequently internalised and the functional response to BMP-2
      consequently down-regulated. The results show, for the first time, that BMPR-IB
      is localised primarily in intracellular compartments in bone cells and that TGF
      beta1 induces rapid surface translocation from the cytoplasm to the cell surface,
      resulting in increased sensitivity of the cells to BMP-2.

PMID- 18619556
TI  - Degradation of very long chain dicarboxylic polyunsaturated fatty acids in mouse
      hepatocytes, a peroxisomal process.
AB  - Polyunsaturated fatty acids can be omega-oxidized to dicarboxylic polyunsaturated
      fatty acids (DC-PUFA), bioactive compounds which cause vasodilatation and
      activation of PPARalpha and gamma. DC-PUFA can be shortened by beta-oxidation,
      and to determine whether mitochondria and/or peroxisomes are responsible for this
      degradation 20-carboxy-[1-(14)C]-eicosatetraenoic acid (20-COOH-AA) was
      synthesized and given to hepatocytes from mouse models with peroxisomal
      dysfunctions. In contrast to wild type cells, hepatocytes from mice with liver
      selective elimination of peroxisomes, due to Pex5p deficiency, failed to produce
      (14)CO(2) and labeled acid-soluble oxidation products, indicating that
      peroxisomes are involved in the degradation of 20-COOH-AA. Subsequently, the
      oxidation of 20-COOH-AA was analyzed in hepatocytes lacking multifunctional
      protein 1 (MFP1) or MFP2, key enzymes of the peroxisomal beta-oxidation.
      Degradation of 20-COOH-AA was partially impaired in MFP1, but not in MFP2
      knockout hepatocytes. Taken together, peroxisomes and not mitochondria are the
      site of beta-oxidation of DC-PUFA, and MFP1 is involved in this process.

PMID- 18619555
TI  - Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine,
      and sphingosine-1-phosphate.
AB  - Ceramidases catalyze hydrolysis of ceramides to generate sphingosine (SPH), which
      is phosphorylated to form sphingosine-1-phosphate (S1P). Ceramide, SPH, and S1P
      are bioactive lipids that mediate cell proliferation, differentiation, apoptosis,
      adhesion, and migration. Presently, 5 human ceramidases encoded by 5 distinct
      genes have been cloned: acid ceramidase (AC), neutral ceramidase (NC), alkaline
      ceramidase 1 (ACER1), alkaline ceramidase 2 (ACER2), and alkaline ceramidase 3
      (ACER3). Each human ceramidase has a mouse counterpart. AC, NC, and ACER1-3 have
      maximal activities in acidic, neutral, and alkaline environments, respectively.
      ACER1-3 have similar protein sequences but no homology to AC and NC. AC and NC
      also have distinct protein sequences. The human AC (hAC) was implicated in Farber
      disease, and hAC may be important for cell survival. The mouse AC (mAC) is needed
      for early embryo survival. NC is protective against inflammatory cytokines, and
      the mouse NC (mNC) is required for the catabolism of ceramides in the digestive
      tract. ACER1 is critical in mediating cell differentiation by controlling the
      generation of SPH and S1P and that ACER2's role in cell proliferation and
      survival depends on its expression or the cell type in which it is found. Here,
      we discuss the role of each ceramidase in regulating cellular responses mediated
      by ceramides, SPH, and S1P.

PMID- 18619557
TI  - MicroRNAs in diseases and drug response.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional
      regulation of gene expression. Since the discovery of the first miRNA gene lin-4
      in C. elegans, over 500 miRNAs have been identified in humans and the list is
      growing. Their biological importance, initially demonstrated in cancer, was also
      more recently discovered in many other pathologies like Alzheimer's disease,
      Parkinson's disease, viral infections, diabetes, and myopathies. In the present
      review we will summarize miRNA profiling studies in human diseases and discuss
      the newly discovered link between microRNAs and drug response. An understanding
      of how microRNAs influence the body's response to certain drugs and how these
      affect the expression of microRNAs, will be of key importance in developing drugs
      with greater safety and efficacy.

PMID- 18619558
TI  - Display scaffolds: protein engineering for novel therapeutics.
AB  - Protein scaffolds represent a new generation of universal binding frameworks for
      use as future immunopharmaceuticals to complement the expanding repertoire of
      therapeutic monoclonal antibodies. Here, we review recent literature describing
      advances in protein scaffold development, including efforts to engineer the
      minimal immunoglobulin-based binding-domain and molecular library design. Several
      diverse protein folds are currently under development on the basis of modular
      construction, a strategy also observed in families of naturally evolved immune
      receptors. We describe potential therapeutic and intracellular applications where
      scaffold-specific features provide distinct advantages for targeting of non
      conventional antigens and comment on the scientific progress and validation of
      several designed scaffolds in the voyage towards first-in-human trials.

PMID- 18619559
TI  - KRAS mutations predict response to EGFR inhibitors.
AB  - Five antiepidermal growth factor receptor therapies have been approved for the
      treatment of solid tumors. However, response rates are relatively low. Several
      biomarkers that enrich for patients with tumors most likely to respond to these
      therapeutic agents have been identified. Mutations in the intermediate signal
      transduction pathway member KRAS also selects patients with tumors depending on
      signaling through this pathway. However, because KRAS acts downstream of the EGF
      receptor, somatic changes in this gene can be used as a marker to exclude
      patients unlikely to benefit from anti-EGFR therapy. Recent clinical data have
      provided substantial evidence that KRAS mutational status should be utilized as a
      diagnostic marker for predicting that response to anti-EGFR therapies in
      colorectal and non-small cell lung cancer.

PMID- 18619560
TI  - Targeting CYP17: established and novel approaches in prostate cancer.
AB  - There is a growing body of evidence that although medical or surgical castration
      blocks the generation of gonadal testosterone in prostate cancer, androgens
      originating from other sources may continue to drive androgen receptor (AR)
      signaling. Recent studies have demonstrated high intratumoral levels of androgens
      and continued AR signaling in castration-resistant prostate cancer (CRPC),
      suggesting that androgens may also be synthesized de novo. Inhibiting the
      systemic biosynthesis of androgens in CRPC by targeting CYP17 may thus represent
      a rational therapeutic approach since this enzyme catalyses two key steroid
      reactions involving 17alpha-hydroxylase and C(17,20)-lyase in the androgen
      biosynthesis pathway. This review will discuss the rationale for and implications
      of targeting CYP17 in CRPC and focus on established and novel CYP17 inhibitors,
      including ketoconazole, abiraterone acetate, and VN/124-1, which are agents
      currently at different stages of development.

PMID- 18619561
TI  - Hepatic cytochrome P450 enzymes belonging to the CYP2C subfamily from an
      Australian marsupial, the koala (Phascolarctos cinereus).
AB  - Cytochromes P450 (CYPs) are critically important in the oxidative metabolism of a
      diverse array of xenobiotics and endogenous substrates. We have previously
      reported that the obligate Eucalyptus feeder koala (Phascolarctos cinereus)
      exhibits a higher hepatic CYP2C activity as compared to non-Eucalyptus feeders
      human or rat, with stimulation of CYP2C activity by cineole. In the present
      study, we examine CYP2C expression by immunohistochemistry and describe the
      identification and cloning of koala CYP2Cs. Utilising anti-rat CYP2C6 antibody,
      the expression of CYP2C was found to be uniform across the hepatic sections,
      being consistent with that observed in human and rat. Two 1647 and 1638 bp koala
      liver CYP2C complete cDNAs, designated CYP2C47 and CYP2C48 respectively, were
      cloned by cDNA library screening. The koala CYP2C cDNAs encode a protein of 495
      amino acids. Three additional partial CYP2C sequences were also identified from
      the koala, indicating the multiplicity of the CYP2C subfamily in this unique
      marsupial species. The results of this study demonstrate the presence of koala
      hepatic CYP2Cs that share several common features with other published CYP2Cs;
      however CYP2C47 and CYP2C48 contain four extra amino acid residues at the NH2
      terminal, a transmembrane anchor which was reported being a fundamentally
      conserved structure core of all eukaryote CYP enzymes.

PMID- 18619562
TI  - Cloning and expression pattern of peroxisome proliferator-activated receptors,
      estrogen receptor alpha and retinoid X receptor alpha in the thicklip grey mullet
      Chelon labrosus.
AB  - Aquatic organisms are exposed to diverse xenobiotics that cause peroxisome
      proliferation and/or endocrine disruption, both modulated in vertebrates by
      transcription factors of the nuclear receptor (NR) superfamily. Peroxisome
      proliferators are agonists of peroxisome proliferator-activated receptors (PPARs)
      that heterodimerize with the retinoid X receptor (RXR). Many xenoestrogens
      activate the estrogen receptor (ER). Here, 1090 bp of PPARalpha, 1255 bp of
      PPARgamma, 278 bp of RXRalpha, and 578 bp of ERalpha of thicklip grey mullet
      Chelon labrosus were cloned. Sequences were highly conserved, although relevant
      changes with respect to mammalian homologs were identified in PPARgamma and
      ERalpha. Semi-quantitative RT-PCR was used to determine if these NRs were
      expressed in different tissues of male, female and undifferentiated mullets
      captured in January and June. Expression of PPARs was highest in liver and lowest
      in muscle. RXRalpha expression was homogeneous excepting a low expression in male
      and female gill in January and brain and heart of undifferentiated fish in
      January and June. ERalpha expression predominated in liver and female gonad in
      June. The expression level of PPARs and ERalpha was significantly higher in liver
      in January than in gills in January or June. The present results show tissue
      dependent modulation of expression of NRs in mullets.

PMID- 18619563
TI  - Structural group auditing of a UMLS semantic type's extent.
AB  - Each UMLS concept is assigned one or more of the semantic types (STs) from the
      Semantic Network. Due to the size and complexity of the UMLS, errors are
      unavoidable. We present two auditing methodologies for groups of semantically
      similar concepts. The straightforward procedure starts with the extent of an ST,
      which is the group of all concepts assigned this ST. We divide the extent into
      groups of concepts that have been assigned exactly the same set of STs. An
      algorithm finds subgroups of suspicious concepts. The human auditor is presented
      with these subgroups, which purportedly exhibit the same semantics, and thus she
      will notice different concepts with wrong or missing ST assignments. The dynamic
      procedure detects concepts which become suspicious in the course of the auditing
      process. Both procedures are applied to two semantic types. The results are
      compared with a comprehensive manual audit and show a very high error recall with
      a much higher precision.

PMID- 18619564
TI  - Molecular dynamics simulations of a lipovitellin-derived amphiphilic beta-sheet
      homologous to apoB-100 beta-sheets at a hydrophobic decane-water interface.
AB  - Lipovitellin, an egg-yolk lipoprotein, transports lipids in a pocket surrounded
      by amphiphilic beta-sheets. Its X-ray structure provides possibilities to study
      interactions between lipophilic beta-sheets and lipids at the atomic level. Here,
      we studied a 67-residue-long amphiphilic beta-sheet of lipovitellin previously
      suggested a suitable working model for studies of the lipid-binding behaviour of
      amphiphilic beta-sheet regions in apolipoprotein B-100 (apoB-100). We performed
      four molecular dynamics simulations with different starting configurations to
      define characteristics of the amphiphilic beta-sheet model at a decane-water
      interface. In each simulation the model beta-sheet bound keenly to the decane
      layer via its hydrophobic surface. The structural profiles showed unchanged
      secondary structure of the beta-sheet during the attachment. Also, aromatic side
      chains, especially tryptophans and tyrosines, mediated the attachment to the
      hydrophobic layer and influenced the orientation of the decane molecules that are
      in contact with the beta-sheet. In conclusion, the present simulations reveal
      high affinity of a lipovitellin-derived amphiphilic beta-sheet to a hydrophobic
      decane layer. They lay thereby the basis for further studies of the interaction
      between amphiphilic beta-sheets and lipids in complex molecular systems, like LDL
      particles, in which the large apoB-100 is the main protein component.

PMID- 18619565
TI  - Affinity separation and enrichment methods in proteomic analysis.
AB  - Protein separation or enrichment is one of the rate-limiting steps in proteomic
      studies. Specific capture and removal of highly-abundant proteins (HAP) with
      large sample-handling capacities are in great demand for enabling detection and
      analysis of low-abundant proteins (LAP). How to grasp and enrich these specific
      proteins or LAP in complex protein mixtures is also an outstanding challenge for
      biomarker discovery and validation. In response to these needs, various
      approaches for removal of HAP or capture of LAP in biological fluids,
      particularly in plasma or serum, have been developed. Among them, immunoaffinity
      subtraction methods based upon polyclonal IgY or IgG antibodies have shown to
      possess unique advantages for proteomic analysis of plasma, serum and other
      biological samples. In addition, other affinity methods that use recombinant
      proteins, lectins, peptides, or chemical ligands have also been developed and
      applied to LAP capture or enrichment. This review discusses in detail the need to
      put technologies and methods in affinity subtraction or enrichment into a context
      of proteomic and systems biology as "Separomics" and provides a prospective of
      affinity-mediated proteomics. Specific products, along with their features,
      advantages, and disadvantages will also be discussed.

PMID- 18619566
TI  - The effect of weight loading and subsequent release from loading on the postnatal
      skeleton.
AB  - INTRODUCTION: The relationship between load and the structure and mechanical
      properties of mature bones has been thoroughly described. In contrast, this
      relationship has been studied much less in immature bones, which consist of bony
      tissue and cartilaginous growth plate, during the postnatal period. This paper
      describes the effect of an externally applied load on the bones of young fast
      growing chicks; in particular, we examine the effect on the growth plate, which
      regulates longitudinal bone growth, and the consequences in terms of bone
      structural and mechanical properties. MATERIALS AND METHODS: The tibial growth
      plates from chicks subjected to external load and control chicks, immediately
      after loading and following 5 days of load release, were studied by histological
      staining and quantitative PCR. The contralateral tibiae were mechanically tested
      by three-point bending and their structural features determined by micro-CT.
      RESULTS: At the end of the external loading period, the tibias of the
      experimental group were shorter and their growth plate narrower than in controls.
      However, at this time point, effects were not yet apparent in the bones'
      structural or mechanical parameters. After a further 5 days of no external load,
      bones and growth plates of the experimental group demonstrated the phenomenon of
      'catch-up': the thickness of the growth plate exceeded that of the control;
      however the relative expression of genes controlling chondrocyte differentiation
      (collagen II and X) did not change, while the expression of factors related to
      growth-plate ossification (osteopontin, alkaline phosphatase) and cartilage and
      bone calcification (matrix and bone Gla proteins) was upregulated as a result of
      the catch-up process. At this time, however, the tibiae of the experimental group
      showed inferior mechanical and structural properties relative to the control
      group. CONCLUSION: External loading during bone elongation negatively affects the
      mechanical and structural properties of the skeleton. The effect is first
      noticeable in the growth plate, which regulates bone growth, and is exhibited in
      the bone phenotype after a lag period.

PMID- 18619567
TI  - High-intensity exercise induces structural, compositional and metabolic changes
      in cuboidal bones--findings from an equine athlete model.
AB  - Fatigue fracture of cuboidal bones occurs in the human foot as well as the equine
      carpus. The racehorse provides a naturally-occurring model to study the effects
      of high-intensity exercise on the morphology and metabolism of cuboidal bones. We
      studied both the mineral and the collagenous matrix of the third (C(3)) and
      radial (C(r)) carpal bones of raced and non-raced Thoroughbred (TB) horses. We
      hypothesised that racehorses would show increases in the mineral component of
      these bones and post-translational modifications of the collagenous matrix
      alongside changes in markers of collagen remodelling and bone formation. C(3) and
      C(r) carpal bones were retrieved from raced TB horses (n=14) and non-raced TB
      horses (n=11). Standardised proximal-distal sections were taken from each bone
      and these were sliced transversely to study the proximal-distal differences in
      bone metabolism from the subchondral plate through to trabecular bone.
      Histomorphometry and bone mineral density measurements were performed in parallel
      with biochemical analyses including total collagen, collagen synthesis and cross
      links, matrix metalloproteinases-2 and 9 and their inhibitors, calcium and
      phosphate, and bone alkaline phosphatase. The results of this study show that,
      while there is a net increase in bone formation in the racehorses, there is
      additionally an increase in bone collagen synthesis and remodelling, particularly
      within the trabecular regions of the bone. The increase in bone density would
      lead to greater stiffness, particularly in the cortical bone, and failure of this
      'stiffer' cortical bone may result from its lack of support from the rapidly
      remodelling and structurally weakened underlying trabecular bone.

PMID- 18619568
TI  - A serosurvey for hantavirus infection in wild rodents from the states of Rio de
      Janeiro and Pernambuco, Brazil.
AB  - Sera from 269 rodents obtained during the routine surveillance operations in
      plague areas of Rio de Janeiro and Pernambuco states, Brazil were tested by ELISA
      for specific IgG antibodies against a recombinant nucleocapsid (N) protein of
      Araraquara hantavirus. ELISA-positive sera were submitted to reverse
      transcriptase-polymerase chain reaction (RT-PCR) for amplification of the virus
      genome and later sequencing for identification of the viral variant. The samples
      from the state of Pernambuco were antibody negative, and although four from Rio
      de Janeiro were ELISA-positive, they failed to yield viral cDNA by RT-PCR. This
      is the first report of the presence of antibodies to a hantavirus among rodents
      from Rio de Janeiro and suggests the possibility of human cases of hantavirus
      pulmonary syndrome (HPS) in that state, although no case has yet been reported.

PMID- 18619569
TI  - Interobserver and intraobserver reliability of detecting age-related macular
      degeneration using a nonmydriatic digital camera.
AB  - PURPOSE: To evaluate the interobserver and intraobserver reliability of detecting
      early and late age-related macular degeneration (AMD) using a nonmydriatic
      digital camera in two distinct groups of older people. DESIGN: Prospective study.
      METHODS: The two groups consisted of a series of patients older than 70 years
      hospitalized in a geriatric unit and a younger series of people older than 55
      years. In both groups, nonmydriatic color fundus photographs were obtained and
      graded independently by two ophthalmologists (V.L. and M.S.). No ophthalmic
      examination was performed. Main outcome measures were frequencies of early and
      late AMD and interobserver and intraobserver agreement. RESULTS: Among 233
      patients in group 1 (mean age, 84.6 years), only 119 patients (51%) could undergo
      photography because of associated multiple morbidities. Mean age of group 2 was
      63.8 years. In group 1, 35 (14.5%) of 238 pictures were ungradable. In series 2,
      65 (9.1%) of 716 pictures were ungradable. Frequencies of early and late AMD were
      30.3% and 5.9% vs 12.6% and 2.6% in series 1 and 2, respectively. Interobserver
      and intraobserver agreement was good or excellent (kappa > 0.6) in both groups.
      CONCLUSIONS: In the entire geriatric cohort, 43% of the patients had gradable
      pictures allowing a diagnosis. These patients would otherwise have had no access
      to any form of funduscopy. In the younger population, nonmydriatic pictures
      permitted a diagnosis in 90% of the individuals. Detection of AMD with a
      nonmydriatic digital camera may lead to large-scale screening and specific
      management.

PMID- 18619570
TI  - Longitudinal study of new eye lesions in children with toxoplasmosis who were not
      treated during the first year of life.
AB  - PURPOSE: To determine the incidence of new chorioretinal lesions in children with
      toxoplasmosis diagnosed after, and therefore not treated during, their first
      year. DESIGN: Prospective longitudinal cohort study. METHODS: Thirty-eight
      children were evaluated in Chicago between 1981 and 2005 for new chorioretinal
      lesions. Thirty-eight children and mothers had serum IgG antibody to Toxoplasma
      gondii. RESULTS: Twenty-eight of 38 children had one of the following: diagnosis
      with serum antibody to T. gondii indicative of chronic infection at age 24
      months, central nervous system calcifications, hydrocephalus, illness compatible
      with congenital toxoplasmosis perinatally but not diagnosed at that time. Twenty
      five returned for follow-up during 1981 to 2005. Their mean (range) age at last
      exam was 10.9 +/- 5.7 (range, 3.5 to 27.2) years and mean follow-up was 5.7 +/-
      2.9 years. Eighteen (72%) children developed at least one new lesion. Thirteen
      (52%) had new central lesions, 11 (44%) had new peripheral lesions, and six (24%)
      had both. Thirteen (52%) had new lesions diagnosed at age > or =10 years. New
      lesions were found at more than one visit in four (22%), and bilateral new
      lesions developed in seven (39%) of 18 children who developed new lesions. Of 10
      additional children with eye findings and serologic tests indicative of chronic
      infection, six returned for follow-up, four (67%) developing new lesions at > or
      =10 years of age. CONCLUSIONS: More than 70% developed new chorioretinal lesions.
      New lesions were commonly diagnosed after the first decade of life.

PMID- 18619572
TI  - High-definition optical coherence tomography features in vitelliform macular
      dystrophy.
AB  - PURPOSE: To correlate high-definition optical coherence tomography (HD OCT) and
      fundus examination findings at different phases of vitelliform macular dystrophy
      and to determine the anatomic location of vitelliform material. DESIGN:
      Prospective, noncomparative, observational case series. METHODS: A complete
      ophthalmologic examination, including fundus biomicroscopy and HD OCT, was
      performed in 11 consecutive patients with a diagnosis of vitelliform macular
      dystrophy. RESULTS: Using HD OCT, we were able to demonstrate for the first time
      the presence of previtelliform lesions, characterized by a thicker layer between
      the retinal pigment epithelium (RPE) and the inner segment and outer segment
      (IS/OS) interface. At this stage, a normal-appearing RPE and IS/OS interface were
      found in two of four eyes. In all progressive stages from the vitelliform to the
      vitelliruptive, the vitelliform material was visualized by HD OCT as an highly
      reflective lesion located between the hyporeflective outer nuclear layer and the
      hyperreflective RPE layer, associated or not to an optically empty lesion. At
      these stages, a disrupted IS/OS interface and an almost normal appearance of all
      major intraretinal layers was detected. At the vitelliruptive and atrophic
      stages, on some parts, the HD OCT scan revealed hyperreflective mottling on the
      RPE layer, probably representing areas of focal RPE hypertrophy. The atrophic
      stage and the fibrotic stage were characterized by thinning of all the retinal
      layers and diffuse loss of the IS/OS interface. In our series, mean best
      corrected visual acuity impairment showed a statistically significant correlation
      to the presence of focal disruption or diffuse loss of the IS/OS interface (P =
      .002), as well as to a more advanced stage of the disease (P = .01). A more
      advanced stage of the disease showed a strong statistically significant
      correlation to the presence of diffuse loss of the IS/OS interface (P < .001).
      CONCLUSIONS: Based on the HD OCT findings, we hypothesize that early changes in
      vitelliform macular dystrophy involve the layer between the RPE and the IS/OS
      interface, first with accumulation of material beneath the sensory retina, and
      then with disruption and attenuation of IS and OS; late changes seem to affect
      the RPE, which undergoes hypertrophy, disruption, and attenuation.

PMID- 18619571
TI  - Intravitreal bevacizumab in inflammatory ocular neovascularization.
AB  - PURPOSE: To assess the role of bevacizumab in inflammatory ocular
      neovascularization. DESIGN: Retrospective, multicenter, consecutive case series
      of inflammatory ocular neovascularization. METHODS: Patients with inflammatory
      ocular neovascularization of varying causes for whom standard therapy failed were
      treated with intravitreal injection of bevacizumab. Main outcome measures
      included improvement of best-corrected visual acuity (BCVA) expressed in
      logarithm of minimum angle of resolution units, response of inflammatory ocular
      neovascularization by funduscopy and angiography, and decrease in central foveal
      thickness as measured by optical coherence tomography at the three-month follow
      up. RESULTS: At the three-month follow-up, 84 eyes of 79 patients had been
      treated with a mean of 1.3 injections (range, one to three). Thirty-four eyes
      showed juxtafoveal choroidal neovascularization (CNV), 34 eyes showed subfoveal
      CNV, eight eyes showed peripapillary CNV, and 11 eyes showed neovascularization
      of the disc (NVD) or neovascularization elsewhere (NVE). BCVA improved 2.4 lines
      from 0.68 (6/28 or 20/94) to 0.44 (6/17 or 20/55) (P < .001). BCVA improved by
      one to three lines in 34.5% of the eyes, by four to six lines in 16.7% of the
      eyes, and by more than six lines in 14.2% of the eyes. Function was unchanged in
      23.8% of the eyes. BCVA worsened in 10.7% (zero to three lines in 7.1%, more than
      four lines in 3.6%). Central foveal thickness decreased from baseline 346 to 252
      microm (P < .001). For CNV, 32 eyes (43.2%) had complete regression after the
      injection, 27 (36.5%) had partial regression, five (6.8%) had no response, and 10
      eyes (13.5%) were not evaluated by the contributors. For NVD or NVE, seven eyes
      (63.6%) had complete regression of new vessels and four eyes (36.4%) had partial
      regression after the injection. CONCLUSIONS: Intravitreal bevacizumab led to
      short-term significant visual improvement and regression of inflammatory ocular
      neovascularization in a wide variety of inflammatory ocular diseases.

PMID- 18619573
TI  - [Speech of Mr. Bernard Accoyer, president of the National Assembly].

PMID- 18619574
TI  - The relative contribution of human cytochrome P450 isoforms to the four caffeine
      oxidation pathways: an in vitro comparative study with cDNA-expressed P450s
      including CYP2C isoforms.
AB  - The aim of the present study was to estimate the relative contribution of
      cytochrome P450 isoforms (P450s), including P450s of the CYP2C subfamily, to the
      metabolism of caffeine in human liver. The experiments were carried out in vitro
      using cDNA-expressed P450s, liver microsomes and specific P450 inhibitors. The
      obtained results show that (1) apart from the 3-N-demethylation of caffeine - a
      CYP1A2 marker reaction and the main oxidation pathway of caffeine in man - 1-N
      demethylation is also specifically catalyzed by CYP1A2 (not reported previously);
      (2) 7-N-demethylation is catalyzed non-specifically, mainly by CYP1A2 and, to a
      smaller extent, by CYP2C8/9 and CYP3A4 (and not by CYP2E1, as suggested
      previously); (3) C-8-hydroxylation preferentially involves CYP1A2 and CYP3A4 and,
      to a smaller degree, CYP2C8/9 and CYP2E1 (and not only CYP3A, as suggested
      previously) at a concentration of 100 microM corresponding to the maximum
      therapeutic concentration in humans. At a higher caffeine concentration, the
      contribution of CYP1A2 to this reaction decreases in favour of CYP2C8/9. The
      obtained data show for the first time the contribution of CYP2C isoforms to the
      metabolism of caffeine in human liver and suggest that apart from 3-N
      demethylation, 1-N-demethylation may also be used for testing CYP1A2 activity.
      Moreover, they indicate that the C-8-hydroxylation is not exclusively catalyzed
      by CYP3A4.

PMID- 18619575
TI  - Age-related neuroanatomical differences from the juvenile period to adulthood in
      mother-reared macaques (Macaca radiata).
AB  - Basic data on age-related neuroanatomical changes across the juvenile to adult
      period in nonhuman primates is sparse, and this gap in knowledge is a serious
      impediment to translational research aimed at understanding brain development
      across the lifespan. In this study, magnetic resonance images were analyzed for
      fifteen mother-reared, socially-housed bonnet macaques (Macaca radiata) in three
      age groups: juvenile, adolescent, and adult. These data are the first to show age
      related changes in gray:white matter ratio and corpus callosum size in bonnet
      macaques. Juvenile monkeys had higher overall gray:white matter ratio as compared
      to adolescent and adult monkeys. Corpus callosum (CC) size varied significantly
      as a function of age and CC region. Total brain volume was significantly lower
      for juvenile monkeys as compared to both adolescents and adults. These results
      are consistent in pattern with age-related changes in gray:white matter ratio and
      regional CC differences observed in humans. Continued study of the animals in
      this cross-sectional study will provide an important means of determining whether
      differences observed between age groups reflect developmental differences due to
      variation in the rate of maturation of CC regions.

PMID- 18619576
TI  - The number of nociceptors in the trigeminal ganglion but not proprioceptors in
      the mesencephalic trigeminal tract nucleus is reduced in dystonin deficient
      dystonia musculorum mice.
AB  - The trigeminal ganglion (TG) and mesencephalic trigeminal tract nucleus (Mes5)
      were investigated in wild type and dystonia musculorum (dt) mice to study the
      effect of dystonin deficiency on primary sensory neurons in the trigeminal
      nervous system. At postnatal day 14, the number of TG neurons was markedly
      decreased in dt mice when compared to wild type mice (43.1% reduction). In
      addition, dystonin disruption decreased the number of sensory neurons which bound
      to isolectin B4, and contained calcitonin gene-related peptide or high-affinity
      nerve growth factor receptor TrkA. Immunohistochemistry for caspase-3
      demonstrated that dystonin deficiency induced excess cell death of TG neurons
      during the early postnatal period. In contrast, Mes5 neurons were barely affected
      in dt mice. These data together suggest that dystonin is necessary for survival
      of nociceptors but not proprioceptors in the trigeminal nervous system.

PMID- 18619577
TI  - Production of oligoglucuronans using a monolithic enzymatic microreactor.
AB  - A glucuronan lyase (EC 4.2.2.14) was immobilized on a monolithic Convective
      Interaction Media (CIM) disk. The immobilization yield was equal to 29% of the
      initial activity and 35% of the initial protein amount. Degradations of three
      glucuronans with various O-acetylation degrees were investigated and compared
      with degradations using free enzyme. The immobilized glucuronan lyase was
      inhibited by the O-acetylation degree like the free enzyme. (1)H NMR analyses
      were used to study the O-acetylation degree of oligoglucuronans and demonstrated
      that the average degrees of polymerization were inclusive between 4 and 13 after
      24h of degradation. This first immobilization of a glucuronan lyase constitutes a
      new tool to produce oligoglucuronans.

PMID- 18619578
TI  - Molecular structure of eight possible configurational isomers of 2,3- and 3,4
      epimino derivatives of 1,6-anhydro-beta-D-hexopyranoses: conformation analysis,
      intra- and inter-molecular hydrogen bonds.
AB  - The crystal structures of a complete series of configurational isomers of 2,3
      epimino and 3,4-epimino derivatives of 1,6-anhydro-beta-D-hexopyranoses were
      determined by single-crystal X-ray analysis. The structures exhibited
      conformational rigidity within the series regardless of the position and
      orientation of the aziridine ring. Possible formation of intramolecular hydrogen
      bonds involving the NH group is discussed with respect to the results of IR
      spectroscopy and to the intermolecular hydrogen bonds found in the crystal
      packing.

PMID- 18619579
TI  - A sulfated glucuronofucan containing both fucofuranose and fucopyranose residues
      from the brown alga Chordaria flagelliformis.
AB  - A fucoidan fraction composed of l-fucose, sulfate, and d-glucuronic acid in a
      molar proportion of about 1:1:0.25 and small amount of acetyl groups was isolated
      from the brown alga Chordaria flagelliformis. Several modified polysaccharides
      were prepared from the native fucoidan using solvolytic desulfation, carboxyl
      reduction, and partial acid hydrolysis. Polysaccharide structures were elucidated
      by methylation analysis and 1D and 2D NMR spectroscopy. The fucoidan was shown to
      contain a backbone of 3-linked alpha-l-fucopyranose residues, about one-third of
      which are glycosylated at C-2 by alpha-d-glucopyranosyluronic acid residues.
      About half of the latter residues are glycosylated at C-4 by single alpha-L
      fucofuranose residues or by disaccharides alpha-L-Fucf-(1-->2)-alpha-L-Fucf-(1-
      >. Fucofuranose residues are mono- and disulfated at different positions, whereas
      some additional sulfate groups occupy C-2 and C-4 of the backbone, the latter
      position being also partially acetylated.

PMID- 18619580
TI  - Degradation behavior of chitosan chains in the 'green' synthesis of gold
      nanoparticles.
AB  - The degradation behavior of chitosan chains in the synthesis of Au nanoparticles
      by a 'green' method was investigated in this paper for the first time. UV-vis
      absorption spectra suggested the formation of Au nanoparticles and TEM images
      showed that their sizes were between 10 and 50nm. During the process of
      synthesis, the intrinsic viscosity [eta] of chitosan was observed to decrease
      gradually, implying that the chitosan chains degraded under the reaction
      conditions. Further studies showed that the degree of degradation of the chitosan
      chains was changed with different reaction temperatures, reactant ratios, and the
      molecular weights of chitosan.

PMID- 18619581
TI  - The structure of the carbohydrate backbone of the LPS from Shewanella spp. MR-4.
AB  - The rough type lipopolysaccharide isolated from Shewanella spp. strain MR-4 was
      analyzed using NMR, mass spectroscopy, and chemical methods. Two structural
      variants have been found, both contained 8-amino-3,8-dideoxy-d-manno-octulosonic
      acid and lacked L-glycero-D-manno-heptose. A minor variant of the LPS contained
      phosphoramide substituent.

PMID- 18619582
TI  - Synthesis of a tetrasaccharide substrate of heparanase.
AB  - A tetrasaccharide, corresponding to the heparan sulfate heparanase substrate,
      namely beta-D-GlcA(2S)-(1-->4)-alpha-D-GlcN(NS,6S)-(1-->4)-beta-D-GlcA-(1-->4)
      alpha-D-GlcN(NS,6S)-OMe, was synthesized in a convergent manner via coupling of a
      pair of the disaccharide building blocks as a key step.

PMID- 18619583
TI  - Aryl 4,6-O-arylidene-1-thio-beta-d-glycopyranoside-based new organogelators and
      their gels.
AB  - Aryl 4,6-O-arylidene-1-thio-beta-d-glycopyranosides based on glucose and
      galactose form organogels in benzene, toluene, o- and p-xylene and 1,2,3,4
      tetrahydronaphthalene. The gel morphologies of micro and nano dimensions were
      studied using SEM and TEM. Absorption spectroscopic studies of two organogels in
      benzene revealed that CH-pi or pi-stacking along with intermolecular H-bonding is
      responsible for the gel assembly.

PMID- 18619584
TI  - Synthesis of novel glycophanes derived from glucuronic acid by ring closing
      alkene and alkyne metathesis.
AB  - Cyclophanes and their analogues are of interest in bioactive molecule development
      and in biomimetic, supramolecular and materials chemistry. Novel hybrids of
      sugars and cyclophanes (glycophanes) have been prepared via the coupling of
      alkenyl and alkynyl glucopyranosiduronic acids with phenylene-1,4-diamine and
      xylene-1,4-diamine and subsequent intramolecular metathesis. Structural studies
      showed that the geometric arrangements of the sugar groups in the macrocycles
      containing secondary amides differ from those in macrocycles that contain
      tertiary amides. This is due to the amides adopting different configurational
      preferences. The compounds had low solubility in water, precluding an
      investigation of their recognition phenomena in this medium.

PMID- 18619585
TI  - A convenient preparation of 6-oligo(lactic acid)cyclomaltoheptaose as kinetically
      degradable derivative for controlled release of amoxicillin.
AB  - 6-Oligo(lactic acid)cyclomaltoheptaose (6-OLA-betaCD) with an average
      substitution of about 7.0 lactic acid units was prepared as a new water-soluble
      cyclomaltoheptaose (betaCD) derivative (solubility of about 70.7-fold that of
      betaCD), based on the ring-opening polymerization of 3,6-dimethyl-1,4-dioxane-2,5
      dione (lactide). The product was characterized by (1)H NMR, (13)C NMR, IR, and MS
      spectroscopy. The complexation of amoxicillin with 6-OLA-betaCD was found to be
      much stronger than that with betaCD at first, and then 6-OLA-betaCD was shown to
      decompose moderately into betaCD and lactic acid. 6-OLA-betaCD might be greatly
      valuable in a controlled release system for Amoxicillin (AMX).

PMID- 18619586
TI  - Theory and computation show that Asp463 is the catalytic proton donor in human
      endoplasmic reticulum alpha-(1-->2)-mannosidase I.
AB  - It has been difficult to identify the proton donor and nucleophilic
      assistant/base of endoplasmic reticulum alpha-(1-->2)-mannosidase I, a member of
      glycoside hydrolase Family 47, which cleaves the glycosidic bond between two
      alpha-(1-->2)-linked mannosyl residues by the inverting mechanism, trimming
      Man(9)GlcNAc(2) to Man(8)GlcNAc(2) isomer B. Part of the difficulty is caused by
      the enzyme's use of a water molecule to transmit the proton that attacks the
      glycosidic oxygen atom. We earlier used automated docking to conclusively
      determine that Glu435 in the yeast enzyme (Glu599 in the corresponding human
      enzyme) is the nucleophilic assistant. The commonly accepted proton donor has
      been Glu330 in the human enzyme (Glu132 in the yeast enzyme). However, for
      theoretical reasons this conclusion is untenable. Theory, automated docking of
      alpha-d-(3)S(1)-mannopyranosyl-(1-->2)-alpha-d-(4)C(1)-mannopyranose and water
      molecules associated with candidate proton donors, and estimation of dissociation
      constants of the latter have shown that the true proton donor is Asp463 in the
      human enzyme (Asp275 in the yeast enzyme).

PMID- 18619587
TI  - Neuroendocrine interactions in the immune system.

PMID- 18619588
TI  - A modular supervised algorithm for vessel segmentation in red-free retinal
      images.
AB  - In this paper, a supervised algorithm for vessel segmentation in red-free images
      of the human retina is proposed. The algorithm is modular and made up of two
      fundamental blocks. The optimal values of two algorithm parameters are found out
      by maximizing proper measures of performances (MOPs) able to evaluate from a
      quantitative point of view the results provided by the proposed algorithm. The
      choice of the MOP allows one to tailor the solution to the specific image
      features to be emphasized. The performances of the algorithm are compared with
      those of other methods described in the literature. The simulation results show a
      good trade-off between quality and processing speed times. For instance, in terms
      of the maximum average accuracy (MAA), K value, and specificity (SP), the best
      performance outcomes are 0.9587, 0.8069 and 0.9477, respectively.

PMID- 18619589
TI  - A diffusion tensor imaging tractography atlas for virtual in vivo dissections.
AB  - Diffusion tensor imaging (DTI) tractography allows perform virtual dissections of
      white matter pathways in the living human brain. In 2002, Catani et al. published
      a method to reconstruct white matter pathways using a region of interest (ROI)
      approach. The method produced virtual representations of white matter tracts
      faithful to classical post-mortem descriptions but it required detailed a priori
      anatomical knowledge. Here, using the same approach, we provide a template to
      guide the delineation of ROIs for the reconstruction of the association,
      projection and commissural pathways of the living human brain. The template can
      be used for single case studies and case-control comparisons. An atlas of the 3D
      reconstructions of the single tracts is also provided as anatomical reference in
      the Montreal Neurological Institute (MNI) space.

PMID- 18619590
TI  - The effect of an iron (III) chelator, silybin, on the proliferation and cell
      cycle of Jurkat cells: a comparison with desferrioxamine.
AB  - Silybin is a flavonoid with antioxidant and free radical scavenging abilities.
      Silybin also acts as an iron chelator by binding Fe (III). The present study was
      undertaken to assess the biological effects of silybin on T leukemia cells in the
      presence or absence of iron and compare its effects with a well-known iron
      chelator; desferrioxamine. In these experiments, we studied the growth capacity
      of Jurkat while varying iron availability in the environment. Desferrioxamine
      significantly inhibited growth and proliferation of Jurkat cells, blocking
      treated cells in the G0/G1 phase and inducing apoptosis. In contrast, silybin
      showed a bimodal effect, inducing cell proliferation at lower concentrations
      whereas inhibition of DNA synthesis and significant cell death was observed at
      higher concentrations. Chelation of Fe totally abrogated antiproliferative,
      cytotoxic and apoptotic effects of desferrioxamine on Jurkat cells. Conversely,
      the silybin-Fe complex had no appreciable effect on its antiproliferative and
      cytotoxic activities. The cytotoxic effect of desferrioxamine was also prevented
      in iron-loaded Jurkat cells; however, the effect of silybin on the growth and
      viability of iron-loaded cells was similar to the effect of its iron complex on
      untreated Jurkat cells. Despite the Fe chelating activity of silybin that
      suggests its possible application in chelation therapy of chronic iron overload,
      the biological effects of silybin on Jurkat cells are different than those of
      desferrioxamine, probably due to antioxidant activity of silybin, which causes
      pro-oxidant effect via iron-catalyzed oxidation with the subsequent generation of
      reactive oxygen species.

PMID- 18619592
TI  - Local field potential beta activity in the subthalamic nucleus of patients with
      Parkinson's disease is associated with improvements in bradykinesia after
      dopamine and deep brain stimulation.
AB  - Parkinson's disease is treated pharmacologically with dopamine replacement
      medication and, more recently, by stimulating basal-ganglia nuclei such as the
      subthalamic nucleus (STN). Depth recordings after this procedure have revealed
      excessive activity at frequencies between 8 and 35 Hz (Brown et al., 2001; Kuhn
      et al., 2004; Priori et al., 2004) that are reduced by dopamine therapy in tandem
      with improvements in bradykinesia/rigidity, but not tremor (Kuhn et al., 2006).
      It has also been shown that improvements in motor symptoms after dopamine
      correlate with single unit activity in the beta range (Weinberger et al., 2006).
      We recorded local field potentials (LFPs) from the subthalamic nucleus of
      patients with Parkinson's disease (PD) after surgery to implant deep brain
      stimulating electrodes while they were on and off dopaminergic medication. As
      well as replicating Kuhn et al., using the same patients we were able to extend
      Weinberger et al. to show that LFP beta oscillatory activity correlated with the
      degree of improvement in bradykinesia/rigidity, but not tremor, after dopamine
      medication. We also found that the power of beta oscillatory activity uniquely
      predicted improvements in bradykinesia/rigidity, but again not tremor, after
      stimulation of the STN in a regression analysis. However improvements after STN
      stimulation related inversely to beta power, possibly reflecting the accuracy of
      the electrode placement and/or the limits of STN stimulation in patients with the
      greatest levels of beta oscillatory activity.

PMID- 18619593
TI  - New tuning rules of PI-like controllers with transient performances for monotonic
      time-delay systems.
AB  - In this note, new tuning methods for Proportional-Integral (PI) are proposed for
      monotonic time delay systems. Like the Ziegler-Nichols method, the proposed
      technique requires only parameters obtained from the plant step response. Unlike
      conventional techniques, the resultant tuning parameters offer the advantage of
      obtaining stable response with prescribed dynamic behavior with relation to the
      maximum overshoot. The idea of the design is simple and relies on basics learned
      in an introductory control course.

PMID- 18619591
TI  - MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation.
AB  - MicroRNAs (miRNAs) are small RNAs with diverse regulatory roles. The miR-124
      miRNA is expressed in neurons in the developing and adult nervous system. Here we
      show that overexpression of miR-124 in differentiating mouse P19 cells promotes
      neurite outgrowth, while blocking miR-124 function delays neurite outgrowth and
      decreases acetylated alpha-tubulin. Altered neurite outgrowth also was observed
      in mouse primary cortical neurons when miR-124 expression was increased, or when
      miR-124 function was blocked. In uncommitted P19 cells, miR-124 expression led to
      disruption of actin filaments and stabilization of microtubules. Expression of
      miR-124 also decreased Cdc42 protein and affected the subcellular localization of
      Rac1, suggesting that miR-124 may act in part via alterations to members of the
      Rho GTPase family. Furthermore, constitutively active Cdc42 or Rac1 attenuated
      neurite outgrowth promoted by miR-124. To obtain a broader perspective, we
      identified mRNAs downregulated by miR-124 in P19 cells using microarrays. mRNAs
      for proteins involved in cytoskeletal regulation were enriched among mRNAs
      downregulated by miR-124. A miR-124 variant with an additional 5' base failed to
      promote neurite outgrowth and downregulated substantially different mRNAs. These
      results indicate that miR-124 contributes to the control of neurite outgrowth
      during neuronal differentiation, possibly by regulation of the cytoskeleton.

PMID- 18619594
TI  - Gender specific associations between matrix metalloproteinases and inflammatory
      markers in post myocardial infarction patients.
AB  - OBJECTIVE: Atherothrombotic disease in the coronary arteries leads to myocardial
      infarction (MI) through plaque rupture or erosion of the endothelium, the former
      mechanism predominating in men and the latter in women. Inflammation is a key
      feature of these processes, and the interplay between inflammation and matrix
      metalloproteinases (MMPs) in this context is not fully understood. In this study,
      we investigated the association between inflammatory markers and MMPs in men and
      women. METHODS: Blood samples were drawn 3 months after a first MI in 387
      patients and 387 sex- and age-matched controls (82% men). C-reactive protein
      (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-alpha (TNF-alpha),
      macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured.
      Coronary angiography was performed in 243 of the patients, and they were
      classified into 0-, 1-, 2- or 3-vessel disease groups. RESULTS: CRP, IL-6, -8, 
      18 and TNF-alpha were higher, and MMP-3 and -9 were lower, in patients than in
      controls. A greater proportion of women (49%) had 0-vessel disease than men (16%,
      p<0.0001). A gender specific pattern of associations between inflammatory markers
      and MMPs was found as IL-6 (r(S)=0.29, p<0.05), IL-18 (r(S)=0.34, p<0.01) and MCP
      1 (r(S)=0.35, p<0.01) correlated with MMP-3 in female patients, whereas CRP
      (r(S)=0.23, p<0.0001), IL-6 (r(S)=0.13, p<0.05) and IL-8 (r(S)=-0.21, p<0.01)
      correlated with MMP-9 in male patients. CONCLUSIONS: The present study
      demonstrates different patterns of association between inflammatory markers and
      MMPs in men and women, strengthening the hypothesis of gender specific
      differences in pathophysiological mechanisms of MI.

PMID- 18619595
TI  - Alterations in the transfer of phospholipids from very-low density lipoproteins
      to activated platelets in type 2 diabetes.
AB  - Type 2 diabetes is a situation at high cardiovascular risk, characterized by
      platelet hyperactivation, oxidative stress, elevated very-low density lipoprotein
      (VLDL) and low high-density lipoprotein concentrations. In the present report, we
      describe the effects of these alterations on the transfers of phospholipids (PL)
      from VLDL to platelets in basal conditions or after thrombin (0.1U/mL) or
      lipoprotein lipase (LPL, 500ng/mL)-mediated platelet activation. In vitro
      transfer of radiolabelled PL from VLDL (200microM PL) to platelets (2x10(8)/mL)
      was measured after incubations of 1h at 37 degrees C in a series of recombination
      experiments using control or diabetic platelets and VLDL, as well as normal or
      oxidized PL. Basal- and thrombin-stimulated transfers from diabetic VLDL were
      similar to those from control VLDL. However, LPL-stimulated transfer was
      decreased when using diabetic VLDL. This was likely due to their lowered ability
      to be lipolyzed. When we compared the platelets from either diabetic patients or
      control subjects, we observed that the transfers of PL from control VLDL to
      diabetic platelets were 20-30% higher than those to control platelets, whether in
      basal conditions or under LPL or thrombin stimulations. Finally, we observed
      that, in all conditions tested, the rate of transfers of oxidized PL was two to
      three times more elevated than that of non oxidized PL. Collective consideration
      of these data suggests that the transfer of PL from VLDL to platelets might be
      elevated in type 2 diabetes, favoring oxidative stress-mediated platelet
      hyperactivation.

PMID- 18619596
TI  - Mapping the depth dependence of shear properties in articular cartilage.
AB  - Determining the depth dependence of the shear properties of articular cartilage
      is essential for understanding the structure-function relation in this tissue.
      Here, we measured spatial variations in the shear modulus G of bovine articular
      cartilage using a novel technique that combines shear testing, confocal imaging
      and force measurement. We found that G varied by up to two orders of magnitude
      across a single sample, exhibited a global minimum 50-250 microm below the
      articular surface in a region just below the superficial zone and was roughly
      constant at depths > 1000 microm (the "plateau region"). For plateau strains
      gamma(plateau) approximately 0.75% and overall compressive strains epsilon
      approximately 5%, G(min) and G(plateau) were approximately 70 and approximately
      650 kPa, respectively. In addition, we found that the shear modulus profile
      depended strongly on the applied shear and axial strains. The greatest change in
      G occurred at the global minimum where the tissue was highly nonlinear,
      stiffening under increased shear strain, and weakening under increased
      compressive strain. Our results can be explained through a simple thought model
      describing the observed nonlinear behavior in terms of localized buckling of
      collagen fibers and suggest that compression may decrease the vulnerability of
      articular cartilage to shear-induced damage by lowering the effective strain on
      individual collagen fibrils.

PMID- 18619597
TI  - The strain-dependent osmotic pressure and stiffness of the bovine nucleus
      pulposus apportioned into ionic and non-ionic contributors.
AB  - Elucidation of the load-bearing mechanism of the nucleus pulposus (NP)
      facilitates understanding of the mechanical and metabolic functioning of the
      intervertebral disc and provides key data for mathematical models. Negatively
      charged proteoglycans in the NP generate an ionic osmotic pressure, pi(i), which
      contributes to the tissue's resistance to load and, moreover, is the main
      mechanism by which the unloaded disc rehydrates. Functionally important, pi(i)
      has seldom been investigated in situ and, crucially, its variation with strain
      has not been reported. In a confined compression apparatus, we aimed to apportion
      the strain-dependent load-bearing mechanism of the NP at equilibrium to the
      tissue matrix and ionic osmotic pressure; and to determine whether any
      proteoglycan loss occurs during confined compression testing. Forty-eight
      confined compression experiments were conducted in isotonic (0.15M NaCl) and
      hypertonic (3.0 and 6.1M NaCl) external solutions in single and multiple step
      strain protocols. The 6.1M NaCl external solution was needed to eliminate as much
      of the ionic effects as possible. The ionic osmotic pressure was well described
      by pi(i)=19.1lambda(-1.58) (R(2)=0.992), and was approximately 70% of the applied
      load at equilibrium, independent of lambda. The effective aggregate modulus,
      H(A)(eff), also increased with strain: H(A)(eff)=59.0lambda(-2.18).
      Concentrations of sulphated glycosaminoglycans were obtained for the samples
      tested in isotonic NaCl with no proteoglycan loss detected from the confined
      compression tests. These results highlight the non-linearity of the stress-strain
      response of NP tissue and the necessity to include a non-linear function for
      osmotic pressure in mathematical models of this tissue.

PMID- 18619598
TI  - A mechanical model representation of the in vivo creep behaviour of muscular bulk
      tissue.
AB  - In vivo mechanical properties of bulk tissue have not yet been explored
      sufficiently. One of the major problems researchers face is the lack of agreement
      between the constitutive models and the standardised methodologies for
      experimental studies. The object of this study was to obtain bulk modulus of the
      upper arm under relaxed and controlled contraction that was 25% of the maximum
      voluntary contraction. A new testing machine was designed to generate constant
      load on the upper arm and measure the deformation over time. This device is
      effectively a cuff that applies controllable pressure on a 47-mm wide band of the
      upper arm. Six different loads (10, 20, 30, 40, 50 and 60 kgf) were applied over
      a time of up to a maximum of 120 s. The deflection-time curves obtained show
      strongly non-linear responses of the bulk tissue. The non-linearity manifested by
      these deflection-time curves is in terms of both time- and load-dependency. A
      specific mechanical model was developed to represent the creep behaviour of the
      bulk tissue. The creep behaviour of the upper arm can be simulated by using four
      Voigt viscoelastic models in series. The three obvious soft tissues of the upper
      arm, namely skin, fat and muscle, were modelled in series. The effects of blood
      vessels and connective tissue were also modelled in series with the previous
      ones. A mechanical model would provide a more controlled method of studying the
      mechanical properties of the bulk tissue. The purpose of the current research,
      therefore, was to develop a mechanical model, which would predict the non-linear,
      viscoelastic behaviour of the human muscular bulk tissue.

PMID- 18619599
TI  - Mechanics of torque generation during quadrupedal arboreal locomotion.
AB  - Quadrupedal animals moving on arboreal substrates face unique challenges to
      maintain stability. The torque generated by the limbs around the long axis of a
      branch during locomotion may clarify how the animals remain stable on arboreal
      supports. We sought to determine what strategy gray short-tailed opossums
      (Monodelphis domestica) use to exert torque and avoid toppling. The opossums
      moved across a branch trackway about half the diameter of their bodies. Part of
      the trackway was instrumented to measure substrate reaction forces and torque
      around the long axis of the branch. Kinematic analysis was used to estimate the
      center of pressure of the manus and pes; from center of pressure and vertical and
      mediolateral forces, the torque generated by substrate reaction forces versus
      muscular effort could be determined. Forelimbs generated significantly greater
      torque than hindlimbs, which is probably explained by the greater weight-bearing
      role of the forelimbs. Fore- and hindlimbs generated torque in opposite
      directions because contralateral fore- and hindlimbs typically contacted the
      branch. Torque generated by muscular effort, however, was often in the same
      direction in both fore- and hindlimbs. The muscle-generated torque is likely the
      result of mediolateral movement of the center of mass caused by mediolateral
      undulation of the torso. These results bear an important implication for the
      study of arboreal locomotion: center of mass dynamics are at least as important
      as static positions. M. domestica is a good representative for a primitive
      mammal, and comparisons with arboreal specialists will shed light on how
      proficient arboreal locomotion evolved.

PMID- 18619600
TI  - Mechanics of toe and heel landing in stepping down in ongoing gait.
AB  - When stepping down from a height difference in ongoing gait, subjects are known
      to use a heel landing at small height differences and switch to toe landing for
      larger height differences. We hypothesized that in toe landing, the leading leg
      can perform more negative work, to control the momentum gained during the
      descent, than in heel landing. Ten young male participants walked over a 10-m
      walkway at 5km/h to step down a height difference of 10cm halfway, using a heel
      or toe landing in five trials each. Kinematic data and ground reaction forces
      under the leading and trailing legs were recorded. Inverse dynamical analysis of
      both strategies showed that the leading leg performed more negative work in toe
      landing, while the vertical velocity at ground contact was lower. In addition,
      the impact forces were lower in toe landing than in heel landing. Toe landing was
      found to reduce gait velocity in the first step on the lower level and required
      higher moments and negative power around the ankle joint than heel landing. Our
      results indicate that heel landing may be preferred when stepping down small
      height differences, because it is less demanding especially for the plantar
      flexor muscles, while toe landing may be preferred for stepping down larger
      height differences, because it improves control over the momentum gained during
      the descent.

PMID- 18619601
TI  - Authors' response to "comments on 'measurement of the microstructural fracture
      toughness of cortical bone using indentation fracture'".

PMID- 18619602
TI  - Muscular force production after concentric contraction.
AB  - The steady-state force following active shortening does not reach the maximum
      isometric force associated with the final length. Isolated extensor digitorum
      longus and soleus muscles from mice (NMRI strain) were used to investigate the
      force produced by a muscle, and some parameters hypothetically influencing this
      shortening-induced force depression. The muscles were pre-stimulated at fixed
      length, shortened and then held isometrically to give maximum post-shortening
      forces, before de-stimulation. The shortening magnitude was 0.18, 0.36 or 0.72mm
      (about 2-7% of optimal length), time of shortening was chosen as 0.03, 0.06 and
      0.12s, and final length as +0.72, 0 and -0.72mm, related to optimal length. The
      mechanical work during active shortening was evaluated by integrating the product
      of force and shortening velocity over the shortening period. The results show a
      positive correlation between the force depression and the mechanical work,
      whereas the force depression was not correlated to the velocity of shortening.
      Depression of the passive force component was also observed following all
      stimulations. Experiments show that the fully stimulated redevelopment of
      isometric force following concentric contraction follows a time function similar
      to the creation of force when isometric muscle is initially stimulated. The
      conclusion is that the isometric force development after active shortening can be
      well described by an asymptotic force which is decided by the produced work, and
      the initial isometric time constant.

PMID- 18619603
TI  - Post-column derivatization capillary electrochromatography for detection of
      biogenic amines in tuna-meat.
AB  - A system to perform post-column derivatization capillary electrochromatography
      (CEC) was developed for the first time. The system mainly included a 4-microm
      (O.D.) silica packed column (200 mm effective length x 0.1 mm inner diameter
      I.D.) with micro-magnetic particles (MMPs) frits, a T-junction connector, an in
      line fluorescence detector and a high-voltage power supply. The system was
      evaluated by using histamine (HA) as a standard biogenic amine for this study. A
      5 microM HA solution was loaded at the anodic site of the capillary column by
      applying 3 kV for 5s. Then, HA was electrophoretically eluted with a 20mM
      phosphate buffer (pH 7) by applying 3 kV, and was derivatized with 3mM o
      phthalaldehyde (OPA)/N-acetylcysteine (NAC) in 100 mM borate (pH 10), which was
      continuously delivered through the reagent-loading capillary tube by gravity into
      the T-junction connector. HA derivative was finally detected with the in-line
      fluorescence detector (lambda(Ex)=340 nm, lambda(Em)=450 nm) at 9.7 min after
      sample loading. To test the utility of this system, it was next employed for its
      ability to detect the presence of HA and other kinds of biogenic amines,
      including cadaverine (Cad), spermidine (Spm) and tyramine (Tyr) in tuna-meat,
      once the validity of the method had been confirmed.

PMID- 18619605
TI  - Colloidal dynamics: influence of diffusion, inertia and colloidal forces on
      cluster formation.
AB  - Computer simulations of colloidal suspensions are discussed. The simulations are
      based on the Langevin equations, pairwise interaction between colloidal particles
      and take into account Brownian, hydrodynamic and colloidal forces. Comparison of
      two models, one taking into account inertial term in Langevin equation and
      another based on diffusional approximation proposed in [D.L. Ermak, J.A.
      McCammon, J. Chem. Phys. 69 (1978) 1352], has shown that both models enable the
      prediction of the correct values of the diffusion coefficient and residence time
      of particle in a doublet and are therefore suitable to study the dynamics of
      formation and breakage of clusters in colloidal suspensions. It is shown that the
      appropriate selection of the time step and taking into account inertia of
      particles provides also the correct value of the average kinetic energy of each
      particle during the simulations, what allows to use the model based on full
      Langevin equations as a reference model to verify the validity of the numerical
      scheme for simulation using diffusion approximation.

PMID- 18619604
TI  - T cell activation on a single-cell level in dielectrophoresis-based microfluidic
      devices.
AB  - The gentle and careful in vitro processing of live cells is essential in order to
      make them available to future therapeutic applications. We present a protocol for
      the activation of single-T cells based on the contact formation with individual
      anti-CD3/anti-CD28 presenting microbeads in a lab-on-chip environment. The chips
      consist of microfluidic channels and microelectrodes for performing
      dielectrophoretic manipulation employing a.c. electric fields. The
      dielectrophoretic guiding elements allow the assembly of cell-bead pairs while
      avoiding ill-defined physical contacts with their environment. After overnight
      cultivation of the manipulated cells, 77% of the bead-associated T cells
      expressed the activation marker molecule CD69. Physiological stress on the cells
      was shown to be mainly due to the single-cell cultivation and not to the
      manipulation in the chips. The same approach could be useful for the in vitro
      regulation of stem cell differentiation.

PMID- 18619606
TI  - Direct AFM measurements of adhesion forces between calcium oxalate monohydrate
      and kidney epithelial cells in the presence of Ca2+ and Mg2+ ions.
AB  - Adhesion forces between the calcium oxalate monohydrate (COM, whewellite) crystal
      and the layer of the epithelial kidney cells have been directly measured under
      buffer solutions by using atomic force microscope (AFM). Two renal epithelial
      lines, MDCK (a collecting duct line) and LLC-PK1 (a proximal tubular line), were
      used. All experiments were conducted in buffer solutions containing additional
      Ca(2+) and Mg(2+) ions in the various concentrations. For MDCK-cells, the
      obtained values of the adhesion force were in the range 0.12-0.51 nN and 0.12
      0.20 nN for Ca(2+) and Mg(2+), respectively. No adhesion force (larger than 0.05
      nN) has been found for LLC-PK1 cells. The "critical" concentrations of ions, near
      which the adhesion force (for MDCK-cells) was maximal, were found to be 100 mM.
      The "critical" concentration of ions and the tendency of the adhesion forces with
      the changing ions concentration, confirm earlier results of Lieske et al. [J.C.
      Lieske, G. Farell, S. Deganello, Urol. Res. 32 (2004) 117-123], in which the
      affinity (rather than the adhesion force) between the COM micro-crystals and the
      layer of the MDCK-cells were measured, calculating the radioactive signal of
      radioactive (14)C COM-crystals stuck to the cells. We believe that the
      aggregation of the COM crystals does not occur in the bulk urine due to short
      travel time through the nephron. If so, the kidney stone formation is determined
      by COM-seeding on the tubules walls. The further growth of the stone on the seed
      can take practically unlimited time because the COM crystal is practically is not
      soluble in water or urine solutions. The value of the adhesion force can be
      useful for evaluation of the adhesion energy or probability of the COM-aggregates
      to stick to the kidney epithelium under the urine flow. This probability is
      calculated taking into account the adhesion force, F(ad), and hydrodynamic
      driving force of the flow. This probability reflects the opportunity of the small
      aggregates to grow and form the kidney stones.

PMID- 18619607
TI  - Experimental transmission of foot-and-mouth disease among Indian buffalo (Bubalus
      bubalis) and from buffalo to cattle.
AB  - Indian buffalo and cattle were infected experimentally with a serotype O strain
      of foot-and-mouth disease virus of buffalo origin. Whereas intradermolingual
      inoculation of buffalo produced largely sub-clinical infection, inoculation in
      the dental pad produced vesicles in the mouth and on the feet. A buffalo infected
      via the dental pad transmitted infection to cattle and buffalo by direct contact
      with them for 24h. The contact-exposed buffalo developed (1) delayed-onset
      clinical signs, and (2) shedding of virus from the nose, commencing before the
      appearance of vesicles and continuing until the experiment was terminated 10
      weeks after exposure. The covert nature of the disease in Indian buffalo, coupled
      with the prolonged shedding of virus, suggests that this species represents a
      host of epidemiological importance.

PMID- 18619608
TI  - Listeria monocytogenes septicaemia and concurrent clostridial infection in an
      adult alpaca (Lama pacos).
AB  - A 10-year-old alpaca with a history of anorexia, weight loss and diarrhoea was
      humanely destroyed and shown to have a multifocal necrotizing hepatitis,
      splenitis and colitis, as well as an ulcerative to diphtheroid ileitis.
      Immunohistochemical examination revealed Listeria monocytogenes antigen in the
      liver and ileum. In addition, L. monocytogenes and Listeria sp.-specific gene
      fragments were detected by the polymerase chain reaction. L. monocytogenes was
      isolated from liver and small intestine and Clostridium perfringens type A with
      beta(2) toxin was found in the small intestine. It is suggested that the
      infection with C. perfringens type A facilitated the systemic spread of L.
      monocytogenes.

PMID- 18619609
TI  - On the road to the definition of the cardiac miRNome in human disease states.

PMID- 18619610
TI  - A mechanistic insight into SMAC peptide interference with XIAP-Bir2 inhibition of
      executioner caspases.
AB  - X-linked inhibitor of apoptosis protein (XIAP) inhibits apoptosis mainly through
      inhibition of caspase-9 and executioner caspases of -3 and -7. The inhibition of
      the former protease is implemented through the bacculoviral inhibitory repeat-3
      (Bir3) domain, while the inhibition of the latter is accomplished by the
      interaction of the linker region located between the Bir1 and the Bir2 domains
      with their active sites. Both modes of inhibition are antagonized by SMAC, which
      is released from mitochondria during the initiation of the intrinsic apoptosis
      pathway. Although the mechanism of SMAC interference in Bir3 inhibition of
      caspase-9 is clearly established, the mechanism by which SMAC interferes with the
      inhibition of the executioner caspases by XIAP remains largely unknown. To
      address this issue, we performed a limited proteolysis of glutathione S
      transferase (GST)-tagged XIAP-Bir2 by trypsin in the presence and in the absence
      of SMAC peptide. Under these conditions, the proteolysis of the linker region was
      diminished considerably. Furthermore, the rate of association of caspase-3 and -7
      with XIAP in the presence of the SMAC peptide was reduced drastically, suggesting
      that SMAC peptide restricts the exposure of the linker region. A limited
      proteolysis of caspase-7 in the presence of GST-Bir2 and GST-NBir3 (the Bir3
      domain of human NAIP) as negative controls was also performed. Matrix-assisted
      laser desorption/ionization time-of-flight analysis of the fragments revealed the
      identity of protected sites, suggesting that the Bir2 domain makes numerous
      contacts with the large subunit of caspase-7. These, combined with the results
      from Far-Western experiments, strongly suggest that the groove for the
      inhibitor(s)-of-apoptosis-protein-binding motif on the Bir2 favors binding to the
      N-terminus of the large subunit rather than to the small subunit of caspase-7.
      Our results further show that the active-site pocket of caspase-7 is first
      occupied by the linker region, followed by the interaction of the N-terminus of
      the enzyme with the SMAC-binding site of the Bir2 domain.

PMID- 18619611
TI  - Structural and energetic analysis of activation by a cyclic nucleotide binding
      domain.
AB  - MlotiK1 is a prokaryotic homolog of cyclic-nucleotide-dependent ion channels that
      contains an intracellular C-terminal cyclic nucleotide binding (CNB) domain. X
      ray structures of the CNB domain have been solved in the absence of ligand and
      bound to cAMP. Both the full-length channel and CNB domain fragment are easily
      expressed and purified, making MlotiK1 a useful model system for dissecting
      activation by ligand binding. We have used X-ray crystallography to determine
      three new MlotiK1 CNB domain structures: a second apo configuration, a cGMP-bound
      structure, and a second cAMP-bound structure. In combination, the five MlotiK1
      CNB domain structures provide a unique opportunity for analyzing, within a single
      protein, the structural differences between the apo state and the bound state,
      and the structural variability within each state. With this analysis as a guide,
      we have probed the nucleotide selectivity and importance of specific residue side
      chains in ligand binding and channel activation. These data help to identify
      ligand-protein interactions that are important for ligand dependence in MlotiK1
      and, more globally, in the class of nucleotide-dependent proteins.

PMID- 18619612
TI  - Attention-deficit/hyperactivity disorder symptoms and child maltreatment: a
      population-based study.
AB  - OBJECTIVE: To examine whether symptoms of attention-deficit/hyperactivity
      disorder (ADHD) during childhood are associated with child maltreatment. STUDY
      DESIGN: The study sample consisted of 14 322 participants in the National
      Longitudinal Study of Adolescent Health. We used logistic regression and
      propensity score matching to examine the relationship, adjusting for demographic,
      socioeconomic, and familial risk factors for child maltreatment. RESULTS:
      Inattentive type, by criteria of Diagnostic and Statistical Manual of Mental
      Disorders Fourth Edition, was significantly associated with the likelihood of
      supervision neglect (odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.2
      2.2), physical neglect (OR: 2.1; 95% CI: 1.4-3.1), physical abuse (OR: 1.6; 95%
      CI: 1.1-2.3), and contact sexual abuse (OR: 2.6; 95% CI: 1.5-4.5). To a lesser
      extent, hyperactive type was associated with the likelihood of supervision
      neglect (OR: 1.5; 95% CI: 1.1-2.0) and physical abuse (OR: 1.3; 95% CI: 1.0-1.6).
      The association between hyperactive type and physical neglect or contact sexual
      abuse was not significant. The results from the propensity score matching were
      similar. CONCLUSIONS: Childhood ADHD symptoms were associated with self-reported
      child maltreatment. Health care providers should be alert to the potential for
      child maltreatment among children with ADHD symptoms, especially those with
      inattentive symptoms.

PMID- 18619613
TI  - Comparison of the prevalence of shortness, underweight, and overweight among US
      children aged 0 to 59 months by using the CDC 2000 and the WHO 2006 growth
      charts.
AB  - OBJECTIVE: To compare the prevalence of shortness, underweight, and overweight by
      using the Centers for Disease Control and Prevention (CDC) 2000 and the World
      Health Organization (WHO) 2006 growth charts. These comparisons are undertaken
      with 2 sets of cutoff values. STUDY DESIGN: Data from the National Health and
      Nutrition Examination Survey 1999-2004 were used to calculate the prevalence
      estimates in US children aged 0 to 59 months (n = 3920). Cutoff values commonly
      used in the United States, on the basis of the 5th percentile of height-for-age
      to define shortness, the 5th percentile of weight-for-height or weight-for-age to
      define underweight, and the 95th percentile of weight-for-height or body mass
      index-for-age to define overweight were compared with the cutoff values
      recommended by WHO, which use <-2 z-score (equivalent to 2.3rd percentile) to
      define shortness and underweight and >or=2 z-score (equivalent to 97.7th
      percentile) to define overweight. A comparison with the same cutoff values (5th
      and 95th) in the 2 charts was also performed. RESULTS: Applying the 5th or 95th
      percentile, we observed a higher prevalence of shortness and overweight for all
      the age groups when the WHO 2006 growth charts were used than when the CDC 2000
      growth charts were used. Applying the 5th percentile to the WHO 2006 charts
      produced lower rates of underweight than did the CDC 2000 charts. However,
      applying the 5th or 95th percentiles to the CDC 2000 charts and the WHO
      recommended cutoff values of -2 or +2 z-score to the WHO charts produced smaller
      differences in the prevalence of shortness and overweight than were seen when the
      5th and 95th percentiles were applied to both the CDC and WHO charts.
      CONCLUSIONS: Estimates of the prevalence of key descriptors of growth in children
      aged 0 to 59 months vary by the chart used and the cutoff values applied. The use
      of the 5th and 95th percentiles for the CDC growth charts and the 2.3rd and
      97.7th percentiles for the WHO growth charts appear comparable in the prevalence
      of shortness and overweight, but not underweight. If practitioners were to use
      the WHO growth charts, it might be more appropriate to adopt the WHO recommended
      cutoff values as well, but this would be a change for office practice.

PMID- 18619614
TI  - Wound closure and metabolic parameter variability in a db/db mouse model for
      diabetic ulcers.
AB  - BACKGROUND: Diabetic foot ulcers are a major cause of nontraumatic lower
      extremity amputations. Wound-healing researchers commonly use db/db mice as a
      model for diabetes, while the excisional wound correlates well with chronic foot
      ulcers. Recent clinical trials identified a correlation between glycemic control
      and cardiovascular complications in diabetic patients. The purpose of this study
      was to determine if the severity of diabetes was related to poor wound healing
      and the broad wound closure variability observed in diabetic db/db mice.
      MATERIALS AND METHODS: Adult female C57BLKS/J, db+/-, and db/db mice were
      anesthetized followed by creation of a 1.5 x 1.5 cm full-thickness excisional
      wound. Wound closure was measured on postoperative days (PODs) 1, 5, 7, 10, 14,
      and 21. Weight, fasting blood glucose, and fasting insulin were also measured
      during the study. RESULTS: By POD 21 both wild-type and db+/- mice demonstrated
      complete wound closure. In db/db mice open wounds were still present at POD 21.
      There was a broad range of percent wound closure from 24 to 81% with a mean of
      55%. Despite strong correlations between diabetic parameters, there was no
      significant correlation between wound closure rate and severity of diabetes.
      CONCLUSIONS: Diabetic db/db mice exhibit a significant impairment of healing in
      the excisional wound model. The variability of wound closure for individual mice
      did not correlate with severity of obesity, hyperglycemia, hyperinsulinemia, or
      insulin resistance. An extensive evaluation of basic diabetes parameters does not
      provide significant insight into the wound-healing process in the db/db mouse
      model.

PMID- 18619615
TI  - Anti-angiogenic property of zoledronic acid by inhibition of endothelial
      progenitor cell differentiation.
AB  - BACKGROUND: Zoledronic acid (ZOL) is clinically available for the treatment of
      skeletal complications. In preclinical studies, strong anti-cancer activities
      against breast cancer, prostate cancer, and leukemia were reported. It also
      inhibited the proliferation of cultured human endothelial cells, suggestive of an
      anti-angiogenic activity. Since ZOL has the tendency to accumulate in bone, we
      investigated the effect of ZOL on endothelial progenitor cells (EPCs), which
      originate from the bone marrow, and play important roles in angiogenesis.
      MATERIALS AND METHODS: Human peripheral blood mononuclear cells were cultured for
      7 d to differentiate into EPCs. Cells were treated without/with ZOL or with
      geranylgeraniol (GGOH). Their endothelial phenotype was confirmed by the
      expression of CD144 and vascular endothelial growth factor receptor 2 and the
      tube-like formation ability on Matrigel (Becton Dickinson, Bedford, MA). Annexin
      V/propidium iodide staining was used to analyze apoptosis. RESULTS: ZOL
      treatment, even at low doses, from d 2 to 7 of culture resulted in impaired EPC
      differentiation and could be restored by co-treatment with GGOH. On the other
      hand, treatment of putative EPCs with ZOL at concentrations higher than 10 mum
      resulted in induction of apoptosis. CONCLUSION: ZOL dose-dependently inhibited
      the differentiation of EPCs, the effect being observed even at low drug levels.
      At high concentrations, ZOL also induced the apoptotic death of putative EPCs.
      Since GGOH restored the inhibitory effect of ZOL on EPCs differentiation, the
      effect of ZOL appears to be dependent on the inhibition of prenylation of small-G
      proteins. From these findings, we conclude that ZOL could be a potential
      anticancer agent by inhibiting angiogenesis.

PMID- 18619617
TI  - The surgical instrument counting process: a statistician's plea for terminology
      clarification.

PMID- 18619616
TI  - Talactoferrin stimulates wound healing with modulation of inflammation.
AB  - BACKGROUND: Inflammation is an acute, early process during normal wound healing.
      Talactoferrin, a recombinant human lactoferrin, can induce the secretion of
      inflammatory mediators. MATERIALS AND METHODS: We measured wound healing activity
      of topical talactoferrin in full-thickness wounds of normal mice and diabetic
      (db(-)/db(-)) mice, systemic bioavailability, and the potential to modulate
      inflammation through in vitro and in vivo binding assays and inflammatory
      mediator measurements. RESULTS: Talactoferrin significantly increased the closure
      rate during 12 to 19 d (maximally on d 3 to 6), the 75% closure incidence, and
      the time to 50% closure versus vehicle or becaplermin (recombinant human platelet
      derived growth factor). Systemic bioavailability was less than 0.5% following
      administration to open wounds. Talactoferrin bound local dermal cells in vivo and
      human dermal fibroblasts in vitro, and it induced the migration of dermal
      fibroblasts, THP-1 macrophages, Jurkat T cells, and mouse granulocytes in vitro.
      Competition binding assays suggested the involvement of IL-8RB and CCR2 chemokine
      receptors in binding and/or cell migration. Consistently, the induction of
      migration was partially inhibited in interleukin (IL)-8RB deficient granulocytes.
      Talactoferrin also enhanced the production of key repair inflammatory mediators
      IL-8, IL-6, macrophage inflammatory protein-1 alpha, and tumor necrosis factor
      alpha in d 3 wounds, and IL-8, IL-6, and monocyte chemotactic protein-1 in
      cultured dermal fibroblasts. CONCLUSION: Talactoferrin promotes wound repair in
      vivo, correlating with a modulated enhancement of the early inflammatory phase of
      wound healing. Based on this data, talactoferrin was subsequently tested
      clinically in a Phase II trial in patients with diabetic ulcers and was found to
      be effective and safe. Talactoferrin should be further evaluated in patients with
      diabetic and other types of ulcers.

PMID- 18619619
TI  - Vascular endothelial growth factor improves myocardial functional recovery
      following ischemia/reperfusion injury.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a central growth and
      survival factor for both the endothelium and the myocardium. Recent evidence also
      suggests that VEGF may play a critical role in stem-cell-mediated paracrine
      cardioprotection. However, the acute effect of exogenous VEGF on myocardium after
      ischemia, indeed whether isolated VEGF alone may be a clinically useful
      therapeutic modality, remains unknown. We hypothesize that infusion of exogenous
      VEGF immediately prior to ischemia will improve myocardial functional recovery.
      MATERIALS AND METHODS: Adult male Sprague Dawley rat hearts were isolated and
      perfused via Langendorff model. All hearts were subject to 15-min equilibration,
      25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received
      a VEGF infusion of 3 x physiological (13 nM, n = 4), 5x physiological (20 nM, n =
      4), or 10x physiological (40 nM, n = 5) immediately prior to ischemia. Controls
      (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular
      developed pressure), end diastolic pressure, +/-dP/dt were continuously recorded.
      RESULTS: End diastolic pressure (mmHg) was elevated in response to
      ischemia/reperfusion. However, hearts infused with 10x VEGF demonstrated
      significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end
      diastolic pressure throughout reperfusion compared to control (49.82 +/- 10.35
      mmHg versus 80.73 +/- 6.08 mmHg at end reperfusion). 10x VEGF-treated hearts also
      exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater
      recovery of left ventricular developed pressure (69.97 +/- 9.69% versus 39.74 +/-
      7.01% of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither
      3 x nor 5x VEGF improved recovery after ischemia. VEGF also did not influence
      coronary flow after ischemia. CONCLUSION: This is the first demonstration that
      exogenous VEGF administration acutely improves myocardial functional recovery
      after ischemia. These findings may help elucidate the role of VEGF in acute stem
      cell-mediated paracrine effects and suggests that isolated VEGF may be of
      therapeutic value.

PMID- 18619618
TI  - Preoperative GATA3 mRNA expression in peripheral blood mononuclear cells is up
      regulated in patients with postoperative infection following hepatobiliary
      pancreatic surgery.
AB  - BACKGROUND: Aggressive hepatobiliary pancreatic surgery has been associated with
      high complication rates. Correlations of Th1/Th2 balance and toll-like receptor
      (TLR) 2/4 expression with postoperative infection following surgery were
      prospectively evaluated. METHODS: Plasma concentrations of interleukin (IL)-6, IL
      10, soluble lymphocyte activation gene (sLAG)-3, and soluble CD30 were determined
      by enzyme-linked immunosorbent assay, and expression levels of T-bet, GATA-3,
      TLR2, and TLR4 mRNA in peripheral blood mononuclear cells were assayed by reverse
      transcription-polymerase chain reaction perioperatively in 56 consecutive
      patients who underwent hepatobiliary pancreatic surgery. RESULTS: Of the 56
      patients, 30 patients had postoperative infection. Postoperative plasma levels of
      IL-6 and IL-10 were significantly higher in patients with postoperative infection
      than in those without infection (P < 0.05). Plasma soluble CD30 level and GATA-3
      mRNA expression level were significantly higher preoperatively, and remained
      higher by postoperative d 7 in patients with postoperative infection (P < 0.05).
      Soluble lymphocyte activation gene levels were not significantly different
      between the two groups. T-bet mRNA expression level was significantly higher on
      postoperative d 3, 7, and 14 in patients with postoperative infection (P < 0.05).
      Preoperative expression levels of GATA-3 mRNA correlated significantly with those
      of TLR2 and TLR4 mRNA (P < 0.05). CONCLUSIONS: These results suggest that in
      patients with postoperative infection, Th1/Th2 balance shifts toward Th2
      dominance preoperatively.

PMID- 18619620
TI  - Delayed protective effects of hyperoxia against cardiac arrhythmias and
      infarction in anesthetized rats.
AB  - BACKGROUND: Previous studies have shown that pretreatment with normobaric
      hyperoxia has cardioprotective effect in isolated rat heart. The present study
      was designed to test the hypothesis that pretreatment normobaric hyperoxia could
      induce delayed cardioprotection effect in an in vivo regional heart ischemia.
      MATERIALS AND METHODS: Experiment 1: Rats were exposed to normobaric normoxia or
      to normobaric hyperoxia (O(2) > 95%) for 15, 30, 60, 120, and 180 min (H15, H30,
      H60, H120, and H180 groups, respectively). After 24 h, they were subjected to 30
      min regional ischemia and 90 min reperfusion. Then, the hearts were harvested for
      measurement of infarct size. Lead II of electrocardiogram was continuously
      recorded for analysis of ischemic arrhythmias. Experiment 2: Different oxygen
      concentrations were tested in the same model of heart ischemia. RESULTS: Compared
      with normoxia group, infarct size significantly reduced in H120 and H180 groups
      (from 48.1 +/- 4 to 31.4 +/- 3.3 and 30 +/- 2.4, respectively); 120 and 180 min
      of >95% hyperoxia significantly reduced the number of ventricular beats (from 314
      +/- 34.9 to 173 +/- 20.3 and 178 +/- 15.7, respectively) and incidence of
      ventricular fibrillation (from 66.8% to 30% and 22.2%, respectively). When the
      oxygen concentration decreased to 80%, its effect on infarct size was abolished;
      however, its antiarrhythmic effect persisted. Further reduction of oxygen
      concentration eliminated both the effects. CONCLUSION: These results show that
      hyperoxia pretreatment may induce delayed anti-infarct and antiarrhythmic effects
      in anesthetized rats. These effects are dependent on the exposure time and oxygen
      concentration.

PMID- 18619621
TI  - Quantification of DNA in biologic scaffold materials.
AB  - Biological scaffold materials composed of extracellular matrix (ECM) are
      routinely used for a variety of clinical applications ranging from the treatment
      of chronic skin ulcers to hernia repair and orthopaedic soft tissue
      reconstruction. The tissues and species from which the ECM is harvested vary
      widely as do the methods used to remove the cellular component of the source
      tissues. The efficacy of decellularization procedures can be quantified by
      examination of the DNA that remains in the ECM. The objective of the present
      study was to determine the DNA content and fragment length in both laboratory
      produced and commercially available ECM scaffold materials. Results showed that
      the majority of DNA is removed from ECM devices but that small amounts remained
      in most tested materials.

PMID- 18619622
TI  - Extracorporeal shockwave treatment for chronic diabetic foot ulcers.
AB  - BACKGROUND: This prospective study compared extracorporeal shockwave treatment
      (ESWT) with hyperbaric oxygen therapy (HBO) in chronic diabetic foot ulcers.
      PATIENTS AND METHODS: Seventy-two patients with 72 chronic diabetic foot ulcers
      were randomly divided into two groups of similar demographics with 34 patients
      with 36 ulcers in the ESWT group and 36 patients with 36 ulcers in the HBO group.
      Patients in the ESWT group received 300 + 100/cm(2) impulses of shockwave at 0.11
      mJ/cm(2) energy flux density every 2 wk for 6 wk, whereas patients in the HBO
      group received HBO daily for 20 treatments. The evaluations included clinical
      assessment of the ulcers with photo-documentation, blood flow perfusion scan,
      bacteriological examination, histological study, and immunohistochemical
      analysis. RESULTS: The overall results showed completely healed in 31%, improved
      in 58%, and unchanged in 11% for the ESWT group and 22% completely healed, 50%
      improved, and 28% unchanged for the HBO group. The ESWT group showed
      significantly better clinical results and local blood flow perfusion, higher cell
      concentration, and activity than the HBO group. On immunohistochemical analysis,
      the ESWT group demonstrated significant increases in endothelial nitric oxide
      synthase, vessel endothelial growth factor, and proliferation cell nuclear
      antigen expressions and a decrease in transference-mediated digoxigenin-deoxy-UTP
      nick end-labeling expression than the HBO group. CONCLUSIONS: ESWT appears to be
      more effective than HBO in chronic diabetic foot ulcers.

PMID- 18619623
TI  - Effects of a hyaluronate-carboxymethylcellulose membrane (Seprafilm) on human
      polymorphonuclear neutrophil functions.
AB  - BACKGROUND: Seprafilm (Genzyme Corp., Cambridge, MA) is safe and effective for
      reducing adhesion formation in abdominal and pelvic surgery. However, the
      relationships between Seprafilm and postoperative complications, including intra
      abdominal abscess formation and intra-abdominal inflammation, remain
      controversial. Polymorphonuclear neutrophils (PMNs) play crucial roles in the
      processes of intra-abdominal inflammation, infection, and abscess formation, and
      PMNs act as the first line in nonspecific host defense against a wide range of
      pathogens. The present study evaluates the effect of Seprafilm itself on human
      PMNs in experimental models in vitro. MATERIALS AND METHODS: Human PMNs were
      isolated from blood samples obtained from 14 healthy volunteers. The functions of
      the isolated cells were assessed by examining their phagocytosis,
      apoptosis/necrosis rates, cytokine production, and PMN-elastase release with and
      without Seprafilm in an in vitro experimental model of inflammation and endotoxin
      stimulation. RESULTS: There were no significant differences in the PMN
      phagocytosis, apoptosis/necrosis rates, cytokine production, or PMN-elastase
      release into the supernatant after coculture with bacteria between assays with
      and without Seprafilm. In the PMN stimulation models involving tumor necrosis
      factor-alpha and lipopolysaccharide, there were no significant differences in
      cytokine production between assays with and without Seprafilm. Furthermore, a
      similar experiment measuring cytokine production in the presence of well
      dissolved Seprafilm produced corresponding results. CONCLUSIONS: Our results
      suggest Seprafilm itself does not affect the functions of isolated human PMNs in
      in vitro experimental models of inflammation and endotoxin-stimulation.

PMID- 18619624
TI  - Leukoencephalopathy with brain stem and spinal cord involvement and high lactate:
      a genetically proven case with distinct MRI findings.
AB  - Leukoencephalopathy with brainstem and spinal cord involvement and lactate
      elevation (LBSL) is a recently described disorder with autosomal recessive mode
      of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial
      aspartyl-tRNA synthetase, have been found as the underlying defect. We report a
      19-year-old male patient with cerebellar, pyramidal and dorsal column
      dysfunctions and specific magnetic resonance imaging (MRI) and characteristic
      magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound
      heterozygous for two mutations in DARS2. MRI showed selective involvement of
      cerebral and cerebellar white matter and superior and inferior cerebellar
      peduncles, without contrast enhancement. The U-fibers were spared. The sensory
      and the pyramidal tracts were affected over their entire length. Involvement of
      the intraparenchymal trajectories of the trigeminal nerves and mesencephalic
      trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were
      identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS
      of the frontal and cerebellar white matter showed elevated lactate, reduced N
      acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL,
      distinct MRI findings should lead to the diagnosis, which can be confirmed by the
      analysis of the disease gene DARS2.

PMID- 18619625
TI  - Reefs in trouble - the real root cause.

PMID- 18619626
TI  - Offshore aquaculture legislation designed to balance production and protection.

PMID- 18619627
TI  - The induction of long-term plasticity of non-synaptic, synchronized activity by
      the activation of group I mGluRs.
AB  - It is well established that activation of group I metabotropic glutamate
      receptors (mGluRs) produces long-lasting alterations in synaptic efficacy. We now
      demonstrate that activation of mGluRs can also induce long-term alterations in
      synchronised network activity that are both induced and expressed in the absence
      of chemical synaptic transmission. Specifically, in hippocampal slices in which
      synaptic transmission was eliminated by perfusing with a Ca2+-free medium, the
      selective group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced a
      persistent (>3h) enhancement (>2-fold) of the frequency of synchronised bursting
      activity. The underlying biochemical mechanism responsible for the induction of
      this form of plasticity was similar to that for DHPG-induced long-term depression
      (LTD) in that it required the activation of tyrosine phosphatases. Also, like
      DHPG-induced LTD, this form of neuronal plasticity could be reversed by
      application of the mGluR antagonist alpha-methyl-4-carboxyphenylglycine (MCPG).
      This unusual form of plasticity, which presumably also occurs when synaptic
      transmission is intact, could contribute to long-term alterations in synchronised
      activity in hippocampal neuronal networks.

PMID- 18619629
TI  - Would complementary and alternative medicine be welcomed in the workplace?

PMID- 18619628
TI  - Reduced activity without hyperphagia contributes to obesity in Tubby mutant mice.
AB  - The Tub gene was originally identified as a spontaneous mutation in C57Bl/6J
      mice, and associated with adult-onset obesity (Tub MUT mice). Although the
      original Tub MUT mouse was identified over 15 years ago, there have been few
      reports on the animal's food intake, body fat percentage or energy expenditure.
      In this study, we report food intake, body weight from 5-20 weeks, body fat, body
      temperature and three different measures of physical activity behavior. Tub MUT
      mice display reduced food intake, uncharacteristic of many obese mouse models,
      and reduced voluntary wheel running with normal home cage ambulatory behavior. We
      conclude that motivation for food and exercise is an underlying defect in TUB MUT
      mice.

PMID- 18619630
TI  - The Olympic and Paralympic Games 2012: literature review of the logistical
      planning and operational challenges for public health.
AB  - OBJECTIVE: To undertake a review of the literature relating to public health
      planning and interventions at previous summer Olympic and Paralympic Games and
      other relevant major summer sporting events or mass gatherings, with a focus on
      official publications and peer-reviewed articles. STUDY DESIGN: Literature
      review. METHODS: A literature review was undertaken using all biomedical
      databases and a freetext search using Google to widen the search beyond peer
      reviewed publications. Search terms used were: Olympics; Paralympics; mass
      gatherings; mass gathering medicine; sporting events; weather; planning; and
      organisation. Citations within articles were searched to identify additional
      references that would inform this review. This literature review concentrates on
      the public health aspects of population care at mass gatherings, particularly the
      Olympic and Paralympic Games which are set over several weeks, focusing on
      surveillance, prevention and health service quality. RESULTS: The literature
      identified 10 areas of public health planning: public health command centre and
      communication; surveillance, assessment and control; environmental health and
      safety; infectious disease outbreaks; implications of weather conditions; health
      promotion; travel information; economic assessments; public transport and
      reduction of asthma events; and preparing athletes for potential allergies. The
      following themes emerged as crucial factors for the success of any public health
      interventions at Olympic and Paralympic Games: detailed planning of deliverables;
      pre-identification of critical success factors; management of risk; detailed
      contingency planning; and full testing of all plans prior to the event.
      CONCLUSIONS: The 2012 Olympic Games will provide an exciting challenge for public
      health providers and systems. Preparation requires early detailed planning of
      policies, procedures and on-site health promotion events, in addition to helping
      to set up the surveillance and monitoring systems that will capture public health
      activity alongside medical activity. Learning from the literature review will
      support the identification of critical success factors and help to formulate
      recommendations that will allow optimal utilization of public health initiatives.
      All plans require full costings in advance which are supported by internal and
      external health-related agencies, voluntary organizations and sponsors. A risk
      assessment should be undertaken as part of the planning process leading to risk
      management plans for mitigating identified potential risks. All surveillance and
      monitoring systems, communication, policies and procedures will require full
      testing prior to commencement of the Games.

PMID- 18619631
TI  - Young adults and acceptance of the human papillomavirus vaccine.
AB  - OBJECTIVES: To determine whether young Dutch adults had ever heard of human
      papillomavirus (HPV) and whether they would accept vaccination, and to assess the
      factors influencing their decision. STUDY DESIGN: Cross-sectional survey.
      METHODS: Six hundred participants aged 18-25 years were recruited from two
      university departments and one non-university technical college. RESULTS: One
      hundred and six (17.7%) participants had heard of HPV and 536 (94%) had heard of
      cervical carcinoma. Women had significantly more knowledge of cervical carcinoma
      than men. A medical education, knowledge of HPV, knowledge of cervical cancer and
      knowledge of the cervical screening programme were not significantly associated
      with acceptance of HPV vaccination, whereas gender and age did show a significant
      relationship. In total, 61% of the female participants and 48% of the male
      participants were willing to accept a 'catch-up' HPV vaccination. CONCLUSIONS:
      This study found that average knowledge levels of HPV and cervical cancer were
      low. Despite this lack of knowledge, a small majority of the study population
      would accept a 'catch-up' HPV vaccination. Women and younger participants were
      significantly more willing to accept HPV vaccination. However, in these
      subgroups, acceptance of HPV vaccination seems to be affected by other, still
      unidentified, factors. These factors could be evaluated in a more qualitative
      orientated study. An educational campaign is needed to cover knowledge about HPV
      and cervical carcinoma, and beliefs and behaviours associated with the acceptance
      of vaccination.

PMID- 18619632
TI  - Household smoking practices of parents with young children, and predictors of
      poor household smoking practices.
AB  - OBJECTIVES: Household smoking practices of parents have a major impact on the
      health of their young children. This study examined the characteristics and
      household smoking practices of parents with children aged 4-5 years, and
      identified the predictive factors of poor household smoking practices among
      Chinese parents in Hong Kong. STUDY DESIGN: Cross-sectional survey. METHODS:
      Smoking parents with young children from a 1997 birth cohort were re-contacted
      for a telephone interview to assess their household smoking practices. RESULTS:
      Among 1149 smoking parents from 1049 families, 898 (85.6%) parents smoked at
      home. Of these, 339 (37.8%) parents reported smoking at home but not near (i.e.
      within 3 metres) their children, and 559 (62.2%) reported that they smoked at
      home without any restrictions. Logistic regression revealed that the predictors
      of poor household smoking practices were: smoking mother [odds ratio (OR) 4.92,
      P<0.001]; children born with normal birth weight (OR 2.62, P<0.05); having more
      than one child (OR 1.70, P=0.01); being a daily smoker (OR 18.96, P<0.0001);
      smoking >or= 11 cigarettes per day (OR 3.10, P<0.0001); having a higher
      Fagerstorm nicotine dependence score (OR 4.57-4.86, P<0.01); and having a smoking
      partner (OR 2.78, P<0.05). CONCLUSIONS: A high proportion of smoking parents with
      young children display poor smoking practices at home. It is of the utmost
      importance that community education and smoking cessation services are targeted
      at these smoking parents to promote smoke-free families.

PMID- 18619633
TI  - Consequences of international migration: a qualitative study on stress among
      Polish migrant workers in Scotland.
AB  - OBJECTIVES: This article aims to gain a greater understanding of the personal
      experiences of Polish migrant workers who work in manual and low-skilled jobs in
      Scotland, and to explore the experiences of stress and its impact on physical and
      psychological health and well-being. STUDY DESIGN: Qualitative in-depth
      interviews and subsequent focus groups. METHODS: Eight in-depth interviews and
      two focus groups were conducted in Spring 2007. Data were analysed thematically
      using Nvivo computer software. RESULTS: The following stress factors were
      identified: difficulties with communication, unfamiliarity with the new
      environment and culture, work-related stress, practical stress, and social
      stress. Several respondents gave accounts of decreased health, particularly
      psychological and psychosomatic distress, and attributed this to the variety of
      stressors and demands on their physical, sociocultural and psychological
      adaptation abilities. CONCLUSIONS: Cross-border migration is a time of transition
      and demands adjustment by the individual migrant as well as the country of
      settlement. Due to high acculturative demands and increased vulnerability,
      migrant workers need to be recognized as a specific target group for health
      promotion and health services.

PMID- 18619634
TI  - A multilevel analysis of long-term psychological distress among Belarusians
      affected by the Chernobyl disaster.
AB  - BACKGROUND: Radiation contamination and sociopolitical instability following the
      Chernobyl nuclear power plant disaster have had a profound impact on Belarus.
      OBJECTIVE: To investigate the factors that impact long-term mental health
      outcomes of this population almost 20 years after the disaster. STUDY DESIGN:
      Cross-sectional study. METHODS: In-person interviews were conducted with 381 men
      and women from two geographic areas of differing radiation contamination within
      Belarus. Participants completed surveys of demographics, psychosocial factors and
      psychological distress. Individual-level characteristics were combined with
      household-level measures of radiation contamination exposure and family
      characteristics to create multilevel predictive models of psychological distress.
      RESULTS: Between-household effects accounted for 20% of variability in depression
      and anxiety scores, but only 8% of variability in somatization scores. Degree of
      chronic daily stressors showed a significant positive relationship with
      psychological distress, whereas mastery/controllability showed a significant
      inverse relationship with distress. At household level, perceived family
      problems, but not level of residential radiation contamination, was the best
      predictor of distress. CONCLUSIONS: Multilevel modelling indicates that long-term
      psychological distress among Belarusians affected by the Chernobyl disaster is
      better predicted by stress-moderating psychosocial factors present in one's daily
      life than by level of residential radiation contamination.

PMID- 18619635
TI  - A proteomic reference map for pig serum proteins as a prerequisite for diagnostic
      applications.
AB  - A reference protein map for pig serum was set up using two-dimensional
      electrophoresis (2-DE). Thirty-nine protein chains or spots deriving from 26
      different proteins were identified by immunological and mass spectrometric
      methods. Thus, the positions of most medium to higher abundance serum proteins
      could be determined on the 2-DE gels. The plasma protein fibrinogen was also
      included in our study. The overall pig protein pattern differs in some respect to
      serum/plasma maps of other mammalian species, e.g. in levels and properties of
      single proteins such as haptoglobin or IgM or in species-specific proteins like
      pig major acute phase protein. Serum protein maps are a useful tool to get an
      overview on expressed proteins, and to monitor changes in concentration as well
      as isotype distribution of the identified proteins. As a consequence, more
      detailed knowledge on protein pattern changes may give deeper insights into the
      metabolic development of some pathologic conditions and may lead to putative
      biomarkers for further investigation. Selected examples for protein pattern
      changes in pigs infected by a viral (porcine circovirus type 2) and a bacterial
      (Actinobacillus pleuropneumoniae) pathogen illustrate the usefulness of the
      method.

PMID- 18619636
TI  - Low concentration of arsenite exacerbates UVR-induced DNA strand breaks by
      inhibiting PARP-1 activity.
AB  - Epidemiological studies have associated arsenic exposure with many types of human
      cancers. Arsenic has also been shown to act as a co-carcinogen even at low
      concentrations. However, the precise mechanism of its co-carcinogenic action is
      unknown. Recent studies indicate that arsenic can interfere with DNA-repair
      processes. Poly(ADP-ribose) polymerase (PARP)-1 is a zinc-finger DNA-repair
      protein, which can promptly sense DNA strand breaks and initiate DNA-repair
      pathways. In the present study, we tested the hypothesis that low concentrations
      of arsenic could inhibit PAPR-1 activity and so exacerbate levels of ultraviolet
      radiation (UVR)-induced DNA strand breaks. HaCat cells were treated with arsenite
      and/or UVR, and then DNA strand breaks were assessed by comet assay. Low
      concentrations of arsenite (<or=2 microM) alone did not induce significant DNA
      strand breaks, but greatly enhanced the DNA strand breaks induced by UVR. Further
      studies showed that 2 microM arsenite effectively inhibited PARP-1 activity. Zinc
      supplementation of arsenite-treated cells restored PARP-1 activity and
      significantly diminished the exacerbating effect of arsenite on UVR-induced DNA
      strand breaks. Importantly, neither arsenite treatment, nor zinc supplementation
      changed UVR-triggered reactive oxygen species (ROS) formation, suggesting that
      their effects upon UVR-induced DNA strand breaks are not through a direct free
      radical mechanism. Combination treatments of arsenite with PARP-1 inhibitor 3
      aminobenzamide or PARP-1 siRNA demonstrate that PARP-1 is the target of arsenite.
      Together, these findings show that arsenite at low concentration exacerbates UVR
      induced DNA strand breaks by inhibiting PARP-1 activity, which may represent an
      important mechanism underlying the co-carcinogenicity of arsenic.

PMID- 18619638
TI  - Amino acid substitutions in the structural or nonstructural proteins of a vaccine
      strain of equine arteritis virus are associated with its attenuation.
AB  - Comparative sequence analysis of a series of strains of equine arteritis virus
      (EAV) of defined virulence for horses, ranging from the horse-adapted virulent
      Bucyrus (VB) strain to a fully attenuated vaccine strain derived from it,
      identified 13 amino acid substitutions associated with attenuation. These include
      4 substitutions in the replicase proteins and 9 in the structural proteins. Using
      reverse genetic techniques, these amino acid substitutions were introduced into a
      virulent infectious cDNA clone pEAVrVBS derived from the VB strain of EAV.
      Inoculation of horses with the recombinant viruses clearly demonstrated that
      changes in either the replicase (nsp1, nsp2 and nsp7) or structural proteins
      (GP2, GP4, GP5 and M) resulted in attenuation of the virulent VB strain. The
      recombinant virus with substitutions in the structural proteins was more
      attenuated than the recombinant virus with substitutions only in the replicase
      proteins.

PMID- 18619637
TI  - Development and pathogenic evaluation of recombinant herpes simplex virus type 1
      expressing two fluorescent reporter genes from different lytic promoters.
AB  - To develop means to explore viral gene expression in ganglia without laborious
      histological sectioning and staining, we created a two color fluorescent
      recombinant HSV-1, in which enhanced green fluorescent protein (EGFP) and red
      fluorescent protein (RFP) are expressed from the glycoprotein B (gB) and
      glycoprotein C (gC) promoters respectively. We show that this virus retained
      growth and pathogenic capacity both in vitro and in vivo compared to wild type
      HSV-1; established latent infections with similar genome copy number in
      trigeminal ganglia (TG); induced a similar HSV-specific CD8(+) T cell infiltrate;
      did not induce CD8(+) T cells reactive to EGFP or RFP; and reactivated from
      latency with normal kinetics in ex vivo TG cultures. Fluorescent EGFP expression
      in plaques surrounding neurons preceded RFP expression and provided highly
      sensitive detection of reactivation and different stages of infection in ex vivo
      TG cultures. Expression of both EGFP and RFP in neurons was readily detectable in
      whole mounts of TG excised during acute infection and following in vivo sodium
      butyrate-induced reactivation from latency. This virus constitutes a useful
      reagent for monitoring lytic viral promoter activity in sensory neurons in vivo
      and in vitro.

PMID- 18619640
TI  - A technical mixture of 2,2',4,4'-tetrabromo diphenyl ether (BDE47) and brominated
      furans triggers aryl hydrocarbon receptor (AhR) mediated gene expression and
      toxicity.
AB  - Polybrominated diphenyl ethers (PBDE) are found as ubiquitous contaminants in the
      environment, e.g., in sediments and biota as well as in human blood samples and
      mother's milk. PBDEs are neuro- and developmental toxins, disturb the endocrine
      system and some are even carcinogenic. Structural similarities of PBDEs with
      dioxin-like compounds, e.g., 2,3,7,8-tetrachloro-dibenzodioxin (TCDD), have
      raised concern about a possible "dioxin-like" action of PBDEs. TCDD exerts its
      toxicity via binding to and activation of the aryl hydrocarbon receptor (AhR).
      AhR ligands are in contrast to PBDEs usually coplanar compounds. Thus, PBDEs are
      not likely to be strong AhR agonists. The aim of this study was to analyze the
      effects of the most abundant PBDE congener, 2,2',4,4'-tetrabromo diphenyl ether
      (BDE47), on AhR activity and signaling. Initially, we measured cytochrome P450
      1A1 (Cyp1A1) induction as a readout for AhR activation by BDE47. Low grade
      purified BDE47 increased CYP1A1 levels in transformed and primary rat hepatocytes
      and human hepatoma cells. Chemical analysis of the BDE47 sample identified trace
      contaminations with brominated furans such as 2,3,7,8-tetrabromo dibenzodioxin
      (TBDF), which most likely were responsible for the observed activation of AhR.
      Subsequently, the BDE47 mixture was studied for its effect on AhR mediated
      toxicity and global gene expression. Indeed, in rat hepatoma cells and in
      zebrafish embryos the BDE47 mixture provoked changes in gene expression and
      toxicity similar to known AhR agonists. In addition to the dioxin-like actions,
      the BDE47 sample enhanced Cyp2B and Cyp3A expression suggesting that commercial
      PBDE mixtures, which also often contain brominated furans, may disturb cellular
      homeostasis at multiple levels.

PMID- 18619639
TI  - Modification of papillomavirus E2 proteins by the small ubiquitin-like modifier
      family members (SUMOs).
AB  - Papillomavirus E2 proteins are critical regulatory proteins that function in
      replication, genome segregation, and viral transcription, including control of
      expression of the viral oncogenes, E6 and E7. Sumoylation is a post-translational
      modification that has been shown to target and modulate the function of many
      transcription factors, and we now demonstrate that E2 proteins are sumoylated.
      Both bovine and human papillomavirus E2 proteins bind to the SUMO conjugation
      enzyme, Ubc9, and using in vitro and E. coli sumoylation systems, these E2
      proteins were readily modified by SUMO proteins. In vivo experiments further
      confirmed that E2 can be sumoylated by SUMO1, SUMO2, or SUMO3. Mapping studies
      identified lysine 292 as the principal residue for covalent conjugation of SUMO
      to HPV16 E2, and a lysine 292 to arginine mutant showed defects for both
      transcriptional activation and repression. The expression levels, intracellular
      localization, and the DNA-binding activity of HPV16 E2 were unchanged by this
      K292R mutation, suggesting that the transcriptional defect reflects a functional
      contribution by sumoylation at this residue. This study provides evidence that
      sumoylation has a role in the regulation of papillomavirus E2, and identifies a
      new mechanism for the modulation of E2 function at the post-translational level.

PMID- 18619641
TI  - COX-2 gene polymorphisms and protein expression in renomedullary interstitial
      cell tumors.
AB  - Normal medullary interstitial cells regulate blood flow, water and salt
      absorption, and ultimately blood pressure through synthesis and secretion of
      prostanoids in which cycloxygenases play the rate-limiting steps. We found that
      most renomedullary interstitial cell tumors overexpressed cycloxygenase-2 (COX
      2), with concomitant expression of microsomal prostaglandin E synthase-1 and the
      receptor for prostaglandin E2. Prostaglandin E2 is the major prostaglandin
      product of COX-2/microsomal prostaglandin E synthase-1 enzymatic pathway in
      medullary interstitial cells, and concomitant expression of COX-2, microsomal
      prostaglandin E synthase-1, and prostaglandin E2 receptor on interstitial cell
      tumors implies the presence of an autocrine growth loop important in pathogenesis
      of these tumors. Furthermore, overexpression of COX-2 protein was observed in
      association with homozygosity in several polymorphic sites within COX-2 gene
      (promoter region sites -1186 T/T and -765 G/G, intron 5 IVS5-275 T/T, and exon 10
      Ex10+837 T>C), indicating their role in development of these tumors.

PMID- 18619642
TI  - Prostate-specific antigen mRNA and protein levels in laser microdissected cells
      of human prostate measured by real-time reverse transcriptase-quantitative
      polymerase chain reaction and immuno-quantitative polymerase chain reaction.
AB  - Laser-assisted microdissection has mainly been used in cancer studies to excise
      pure cell populations from heterogeneous tissues. Cancer and normal cells
      selected by laser-assisted microdissection have frequently been used for mRNA
      expression studies usually by reverse transcriptase-quantitative polymerase chain
      reaction (qPCR). Recently, real time immuno-qPCR was developed as a new tool for
      highly sensitive measurements of proteins. Using reverse transcriptase-qPCR and
      immuno-qPCR, we measured the amounts of prostate-specific antigen mRNA and its
      corresponding protein in homogeneous and comparable cell populations, collected
      from normal and cancer prostates by laser-assisted microdissection. With these
      techniques, prostate-specific antigen mRNA and protein were quantified over a
      wide range of concentrations with a sensitivity sufficient to analyze single
      prostate cells (LNCaP). We did not find significant differences in prostate
      specific antigen protein and mRNA between normal and cancer cells. The expression
      of prostate-specific antigen protein and mRNA was highly correlated in both
      normal and pathological cells. In microdissected peritubular stromal areas of
      prostate cancers, the concentration of prostate-specific antigen protein was
      about 100 times higher than in normal prostate, indicating an increased transit
      of secreted prostate-specific antigen. In the same samples, prostate-specific
      antigen mRNA was not detectable. Our data demonstrate, for the first time, the
      feasibility of simultaneous application of reverse transcriptase-qPCR and immuno
      qPCR in studies of homogeneous cell populations, collected by laser-assisted
      microdissection. The approach is expected to become a very powerful tool for
      expression studies in human cancers at both mRNA and protein levels.

PMID- 18619644
TI  - Immunohistochemical profiling of cytokeratin expression by endometrial stroma
      sarcoma.
AB  - Endometrial stromal sarcomas can be confused with several neoplasms because of
      their inconsistent and widely varied morphologic appearance and frequent
      immunohistochemical expression of a variety of antigens including cytokeratin.
      The resulting diagnostic challenge becomes problematic particularly in the
      diagnosis of metastases resulting from such tumors. Because of the sometime
      epithelioid appearance of the tumor cells and their expression of cytokeratin,
      the metastases may be misdiagnosed as poorly differentiated carcinoma. We
      therefore studied the profile of cytokeratin proteins expression in 17 cases of
      endometrial stromal sarcomas using a panel of antibodies including cytokeratin
      cocktail antibody (AE1/AE 3), CK5/6, CK7, CK14, CK16, Cam5.2 (CK8), CK19, CK20,
      and 34Ebeta12 (CK1, 5, 10, and 14). Of the 17 cases, 8 (47%) stained positive
      with the cytokeratin cocktail antibody (AE1/AE 3). Of the 8 cases with
      cytokeratin expression, 5 (63%) stained positive with CK19, and 3 of them stained
      positive with Cam5.2. The 3 cases that stained positive with Cam5.2 also
      expressed CK19. Of the 5 cases with CK19, 1 was focally positive for CK5/6, CK7,
      and 34Ebeta12. None of the cases expressed CK14, CK16, or CK20. These results
      show that CK19 is most commonly expressed cytokeratin in endometrial stromal
      tumors. Hence, the inclusion of CK19 in the panel of immunostains may help
      resolve the diagnostic confusion created by keratin expression in endometrial
      stromal sarcoma and may also help in the correct diagnosis of endometrial stromal
      sarcoma at extrauterine sites.

PMID- 18619643
TI  - CD10 immunostaining distinguishes atypical polypoid adenomyofibroma (atypical
      polypoid adenomyoma) from endometrial carcinoma invading the myometrium.
AB  - The major differential diagnostic problem presented by atypical polypoid
      adenomyofibroma (atypical polypoid adenomyoma) (APA), which usually affects young
      women, is the exclusion of well-differentiated endometrial carcinoma invading the
      myometrium. This distinction, however, is of great clinical importance from the
      standpoint of treatment because reproductive conservation is feasible for
      patients with APA. Recently, CD10, known to be a marker of endometrial stromal
      cells, was reported to be also expressed in cells immediately surrounding the
      neoplastic glands invading the myometrium [Am J Surg Pathol 27 (2003) 786-789;
      Mod Pathol 16(1) (2003) 22-27]. However, CD10 expression in the myofibromatous
      component of APA has not been previously examined in the literature. We therefore
      decided to examine whether the CD10-immunostaining pattern in APA is different
      from that in myoinvasive carcinoma. Furthermore, we also attempted to obtain any
      histopathologic findings that may offer some insight regarding the histogenesis
      of APA. Seven cases of APA were immunostained for CD10 using curettage or
      polypectomy specimens, in addition to hysterectomy specimens in 1 case. Areas
      with more fibrotic rather than muscular stroma were focally observed in 4 cases.
      The pattern of staining was compared with hysterectomy specimens taken from 19
      cases in which well- to moderately differentiated endometrioid adenocarcinoma had
      deeply invaded the myometrium (outer two thirds of the myometrium) but was not
      associated with adenomyosis. In 6 of 7 cases of APA, CD10 was never expressed in
      the myofibromatous stromal components. In 1 case of APA, the fascicles of
      fibrotic and muscular mesenchymal cells in the interglandular areas were focally
      and weakly positive for CD10. All 19 myoinvasive carcinomas expressed CD10 to
      some extent in cells immediately surrounding the neoplastic myoinvasive glands
      (fringe-like staining pattern). The proportion of the myoinvasive nests
      immediately surrounded by CD10-positive mesenchymal cells was as follows: mean,
      74%; median, 80%; minimum, 5%; maximum, 100%. The fringe-like CD10-staining
      pattern was not observed in APA. Furthermore, we identified a gradual
      transformation from preexisting endometrial stromal cells (CD10 positive) into
      the typical myofibromatous stromal component (CD10 negative) of APA in 1 case. In
      conclusion, this study demonstrated differences in the CD10 immunoreactivity or
      immunostaining pattern between the stromal components of APA and myoinvasive
      endometrial carcinoma. This difference should lead to a more accurate diagnosis
      of APA (pseudo-myoinvasive lesion). Furthermore, the histogenesis of APA may
      perhaps be explained by "myofibromatous metaplasia" of the endometrial stromal
      cells.

PMID- 18619645
TI  - Synchronous autoimmune pancreatitis and infiltrating pancreatic ductal
      adenocarcinoma: case report and review of the literature.
AB  - An 80-year-old white man underwent pylorus-preserving pancreaticoduodenectomy
      after presenting with obstructive jaundice and a dilated biliary tree on
      cholangiopancreatography. Histologic evaluation of the specimen revealed
      synchronous autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis)
      and infiltrating ductal adenocarcinoma of the pancreas. The mixed inflammatory
      infiltrate centered on the pancreatic ducts was associated with acinar loss,
      parenchymal fibrosis, and obliterative venulitis. Immunohistochemical labeling
      with an antibody to IgG4 revealed greater than 50 IgG4-positive plasma cells per
      high power field. Although not appreciated grossly, pancreatic intraepithelial
      neoplasia-3 and a neurotropic infiltrating poorly differentiated adenocarcinoma
      of the pancreas were also present. This case highlights the importance of
      carefully evaluating patients with autoimmune pancreatitis to rule out an
      underlying neoplasm and the importance of following those who were treated
      nonsurgically until the disease fully resolves.

PMID- 18619646
TI  - The role of beta-catenin in chronic myeloproliferative disorders.
AB  - The goal of the current study is to evaluate the role of beta-catenin in chronic
      myeloproliferative disorders. Expression of beta-catenin was analyzed by
      immunohistochemistry in formalin-fixed decalcified bone marrow biopsy specimens
      from 52 chronic myeloproliferative disorder cases and 6 nonchronic
      myeloproliferative disorder bone marrows as controls. The frequency of moderate
      to strong beta-catenin staining of megakaryocytes was significantly higher in
      polycythemia vera cases and in essential thrombocythemia cases than in chronic
      myelogenous leukemia cases (polycythemia vera versus chronic myelogenous
      leukemia, P = .002345, Fisher exact; and essential thrombocythemia versus chronic
      myelogenous leukemia, P = .002288), chronic idiopathic myelofibrosis cases
      (polycythemia vera versus chronic idiopathic myelofibrosis, P = .006707 and
      essential thrombocythemia versus chronic idiopathic myelofibrosis, P = .006932)
      or control cases (polycythemia vera versus control, P = .010489 and essential
      thrombocythemia versus control, P = .0113120). The erythroid and myeloid lineages
      showed absent to weak beta-catenin staining in most cases. In conclusion, these
      results indicate that the Wnt/beta-catenin signaling pathway may have a role in
      megakaryocytopoiesis in polycythemia vera and essential thrombocythemia. In
      addition, beta-catenin may be a useful marker for differentiating polycythemia
      vera and essential thrombocythemia from other types of chronic myeloproliferative
      disorders.

PMID- 18619647
TI  - Genetic alterations in colorectal cancers with demethylation of insulin-like
      growth factor II.
AB  - Loss of genomic imprinting is an epigenetic alteration of some cancers involving
      the absence of parental origin-specific expression of imprinted genes. Loss of
      genomic imprinting of insulin-like growth factor II is often detected in
      colorectal cancer. However, the genetic alterations accompanied by colorectal
      cancer with insulin-like growth factor II loss of genomic imprinting have not
      been fully determined. Genomic DNA samples were collected from 52 colorectal
      cancer tissues and analyzed. The loss of insulin-like growth factor II genomic
      imprinting status was determined by assessing the demethylation of the insulin
      like growth factor II differentially methylated region using bisulfite
      sequencing. The molecular signatures were also examined: genetic mutations of
      KRAS, BRAF, and PIK3CA; the expression of CTNNB1 and TP53; and microsatellite
      instability status. Several cases of colorectal cancer with normal insulin-like
      growth factor II imprinting were located in the distal colon; in contrast,
      colorectal cancer with loss of genomic imprinting tended to be found in the
      proximal colon (22.7 versus 56.6%). The PIK3CA gene mutation was highly detected
      in normal imprinting tumors compared to colorectal cancers with insulin-like
      growth factor II loss of genomic imprinting (27.3% versus 6.7%). In multivariate
      analysis of these clinicopathologic and molecular factors of tumors,
      statistically significant relationships were observed among the proximal location
      of the tumor (odds ratio, 12.9; 95% confidence interval, 1.52-110.13), PIK3CA
      genetic mutation (odds ratio, 0.082; 95% confidence interval, 0.01-0.73), and
      insulin-like growth factor II genomic imprinting status. Our findings indicate
      that colorectal cancers with demethylation of the insulin-like growth factor II
      gene are distinct from normal imprinting tumors, both in clinical and genetic
      features.

PMID- 18619648
TI  - IgA-dominant postinfectious glomerulonephritis: a report of 13 cases with common
      ultrastructural features.
AB  - A unique form of postinfectious glomerulonephritis characterized by IgA-dominant
      immune complex deposits was recently described by Nasr et al (Hum Pathol.
      2003;34:1235-1241), each case after a Staphylococcus infection in diabetic
      patients. Others have described glomerulonephritis with IgA-containing immune
      complex deposits in association with staphylococcal infections, although their
      histology was more varied and electron microscopy often did not to show large
      subepithelial deposits ("humps") typical of postinfectious glomerulonephritis. In
      this report, we describe demographic, clinical, and renal biopsy findings in 13
      cases of IgA-dominant postinfectious glomerulonephritis, each characterized by
      subepithelial humps at various stages of resolution. All patients presented with
      renal insufficiency (mean serum creatinine +/- SD, 4.4 +/- 2.7 mg/dL), hematuria
      (macroscopic in 3), and proteinuria (nephrotic range in 6). Based on histology
      and electron microscopy, postinfectious glomerulonephritis was classified as
      acute in 2 patients, subacute in 3, and resolving/persistent in 8. There were 6
      patients who had recent Staphylococcus aureus infections (3 methicillin
      resistant), 5 who were diabetic, and 3 with nephropathy. A total of 4 patients (3
      with serum creatinine >8.0 mg/dL at biopsy) developed end-stage renal disease,
      whereas 9 had a mean serum creatinine of 2.0 +/- 1.1 mg/dL (range, 0.8-4.4) at 10
      +/- 13 months (range, 2-44) after biopsy. In summary, IgA-dominant postinfectious
      glomerulonephritis resembles poststreptococcal glomerulonephritis in its
      histologic spectrum and electron microscopy findings, is often associated with
      staphylococcal infections, occurs in diabetics and nondiabetics, and may resolve
      if renal failure at presentation is not severe.

PMID- 18619649
TI  - Up-regulation of the hypoxia-inducible factor-1 transcriptional pathway in
      colorectal carcinomas.
AB  - The aim of the study was to identify the impact on prognosis of hypoxia-inducible
      factor-1 genetic program in colorectal carcinomas and to develop an experimental
      procedure that would allow a reliable quantitative gene expression analysis in
      formalin-fixed and paraffin-embedded tissue. The expression of hypoxia-inducible
      factor-1alpha and 13 hypoxia-inducible factor-1 target genes (AMF, CAIX, VEGF,
      VEGFR1, VEGFR2, HGF, MET, TGFalpha, EGFR, IGF2, MMP2, PLAUR, NIX) was quantified
      by real-time polymerase chain reaction in 18 colorectal, poorly differentiated
      neuroendocrine carcinomas and in 60 invasive colorectal carcinomas. Moreover,
      hypoxia-inducible factor-1alpha protein expression was evaluated by
      immunohistochemistry. High levels of hypoxia-inducible factor-1alpha were
      positively associated with poorly differentiated neuroendocrine carcinoma
      histology (P < .005), poor differentiation (P < .025), presence of necrosis, and
      presence of microsatellite instability (P < .05). AMF, TGFalpha, IGF2, NIX, VEGF,
      and VEGFR2 transcripts were significantly higher in the very aggressive poorly
      differentiated neuroendocrine carcinomas than in exocrine colorectal carcinomas
      and TGFalpha expression was significantly associated with presence of lymph nodal
      metastases (P < .05). High levels of TGFalpha and NIX were significantly
      associated with decreased overall survival (P < .001; P < .01). The multivariate
      analysis showed that advanced stage, presence of lymph node metastases, and high
      TGFalpha expression had an independent effect on survival (P < .006; P < .01; P <
      .0006). Our study suggests an up-regulation of the hypoxia-inducible factor-1
      transcriptional pathway in colorectal carcinomas. hypoxia-inducible factor-1alpha
      overexpression alone, has no impact on the prognosis of colorectal carcinomas
      likely because the consequences of hypoxia-inducible factor-1alpha
      expression/stabilization strongly depend on the genetic background of the
      transformed cells. Mechanisms leading to increased synthesis of hypoxia-inducible
      factor-1alpha mRNA via autocrine growth factor loops may play a crucial role in
      invasive growth in this site.

PMID- 18619650
TI  - Skipjack tuna as a bioindicator of contamination by perfluorinated compounds in
      the oceans.
AB  - Perfluorinated chemicals (PFCs) have emerged as global environmental
      contaminants. Studies have reported the widespread occurrence of PFCs in biota
      from marine coastal waters and in remote polar regions. However, few studies have
      reported the distribution of PFCs in biota from offshore waters and open oceans.
      In this study, concentrations of nine PFCs were determined in the livers of 60
      skipjack tuna (Katsuwonus pelamis) collected from offshore waters and the open
      ocean along the Pacific Rim, including the Sea of Japan, the East China Sea, the
      Indian Ocean, and the Western North Pacific Ocean, during 1997-1999. At least one
      of the nine PFCs was found in every tuna sample analyzed. Overall,
      perfluorooctanesulfonate (PFOS) and perfluoroundecanoic acid (PFUnDA) were the
      predominant compounds found in livers of tuna at concentrations of <1-58.9 and <1
      31.6 ng/g, wet wt, respectively. Long-chain perfluorocarboxylates such as
      perfluorodecanoic acid (PFDA) and perfluorododecanoic acid (PFDoDA) were common
      in the tuna livers. In livers of tuna from several offshore and open-ocean
      locations, concentrations of PFUnDA were greater than the concentrations of PFOS.
      The profiles and concentrations of PFCs in tuna livers suggest that the sources
      in East Asia are dominated by long-chain perfluorocarboxylates, especially
      PFUnDA. High concentrations of PFUnDA in tuna may indicate a shift in sources of
      PFCs in East Asia. The spatial distribution of PFOS in skipjack tuna reflected
      the concentrations previously reported in seawater samples from the Pacific and
      Indian Oceans, suggesting that tuna are good bioindicators of pollution by PFOS.
      Despite its predominance in ocean waters, PFOA was rarely found in tuna livers,
      indicative of the low bioaccumulation potential of this compound. Our study
      establishes baseline concentrations of PFCs in skipjack tuna from the oceans of
      the Asia-Pacific region, enabling future temporal trend studies of PFCs in
      oceans.

PMID- 18619652
TI  - Tuberculous epididymitis presenting as huge scrotal tumor.
AB  - Genitourinary tract tuberculosis is a specific chronic granulomatous infection.
      However, epididymal tuberculosis presented as a huge scrotal mass is uncommon. We
      report one case of epididymal tuberculosis that was noted 5 months after the
      prostate biopsy and was managed with unilateral simple epidymo-orchiectomy.
      Antituberculous drugs have been given as the medical treatment of tuberculosis
      postoperatively. Urinalysis became normalized and the scrotal ultrasonography
      showed normal left epididymis and testicle at 6-month follow up.

PMID- 18619651
TI  - Effect of low frequency ultrasound on combined rt-PA and eptifibatide
      thrombolysis in human clots.
AB  - INTRODUCTION: Fibrinolytics such as recombinant tissue plasminogen activator (rt
      PA) are used to treat thrombotic disease such as acute myocardial infarction
      (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side
      effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and
      ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and
      fibrinolytic treatment are often used in AMI, and are under investigation for
      stroke treatment. However, little is known of the efficacy of combined GP IIb
      IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic
      efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in
      vitro human clot model. MATERIALS AND METHODS: Blood was drawn from 15 subjects
      after IRB approval. Clots were made in 20 microL pipettes, and placed in a water
      tank for microscopic visualization during lytic treatment. Clots were exposed to
      control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA + Epf),
      with (+US) or without (-US) ultrasound for 30 minutes at 37 degrees C in human
      plasma. Clot lysis was measured over time, using a microscopic imaging technique.
      The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify
      lytic efficacy. RESULTS AND CONCLUSIONS: LR values for (- US) treated clots were
      0.8+/-0.1(control), 1.8+/-0.3 (Epf), 1.5+/-0.2 (rt-PA), and 1.3+/-0.4 (rt-PA +
      Epf) (% clot width/minute) respectively. In comparison, the (+ US) group
      exhibited LR values of 1.6+/-0.2 (control), 4.3+/-0.4 (Epf), 6.3+/-0.4 (rt-PA),
      and 4.6+/-0.6 (rt-PA + Epf). For (- US) treated clots, FCL was 6.0+/-0.8
      (control), 9.2+/-2.5 (Epf), 15.6+/-1.7 (rt-PA), and 28.0+/-2.2% (rt-PA + Epf)
      respectively. FCL for (+ US) clots was 13.5+/-2.4 (control), 20.7+/-6.4 (Epf),
      44.4+/-3.6 (rt-PA) and 30.3+/-3.6% (rt-PA + Epf) respectively. Although the
      addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the
      absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that
      of combined ultrasound, rt-PA and eptifibatide exposure.

PMID- 18619653
TI  - High-flow priapism: superselective cavernous artery embolization with microcoils.
AB  - OBJECTIVES: To determine the effectiveness of superselective cavernous artery
      embolization. METHODS: Eight patients with high-flow priapism were included in
      this study. All were treated by superselective cavernous artery embolization with
      microcoils and gelatin sponges. The follow-up examinations consisted of color
      duplex ultrasonography. The International Index of Erectile Function 5-item
      questionnaire was used to investigate the patients' erectile function before the
      onset of priapism, at embolization, and 6 months after embolization. RESULTS: A
      unilateral cavernous fistula was found in 7 patients and bilateral fistulas in 1.
      Of the 8 patients, 2 (1 with unilateral and 1 with bilateral fistulas) initially
      underwent embolization with a gelatin sponge but presented with recurrence of
      tumescence 1 week after treatment and required a repeat embolization procedure
      with microcoils. The other 6 patients (75%) were successfully detumescent after
      embolization with microcoils. The 6 patients (75%) who underwent embolization
      with microcoils alone had normal erectile function with a mean International
      Index of Erectile Function score of 22.20 at 6 months after embolization. The 2
      patients (25%) who had required repeat embolization had erectile dysfunction,
      with a mean International Index of Erectile Function score of 13.00. CONCLUSIONS:
      Superselective cavernous artery embolization with microcoils is a safe and
      effective treatment of high-flow priapism. The use of microcoils resulted in
      greater embolization success and preservation of erectile function, especially in
      the treatment of a unilateral arterial fistula in a young patient.

PMID- 18619654
TI  - Occurrence of urinary tract infection in children with significant upper urinary
      tract obstruction.
AB  - OBJECTIVES: Ureteropelvic junction obstruction and obstructive megaureter are
      common causes of upper urinary tract obstruction. Recent data have demonstrated
      that the rate of urinary tract infection (UTI) among children with upper tract
      obstruction not treated with prophylactic antibiotics is >36%. The aim of this
      study was to evaluate the occurrence of UTI in our patients with ureteropelvic
      junction obstruction and megaureter to better assess the role of prophylactic
      antibiotics. METHODS: A retrospective analysis was conducted. The inclusion
      criteria were grade 3 or 4 hydronephrosis secondary to obstructive megaureter or
      ureteropelvic junction obstruction in children not maintained on prophylactic
      antibiotics. UTI was defined as a culture-documented symptomatic infection.
      Fisher's exact tests were used to evaluate for an association between the
      occurrence of UTI with sex, level of obstruction, grade of hydronephrosis, and
      circumcision status. RESULTS: A total of 92 patients met the study criteria. The
      rate of UTI in all patients was 4.3% (95% confidence interval 0.2%-8.6%). No
      statistically significant difference in the infection rate was noted according to
      sex, obstruction level, hydronephrosis grade, or circumcision status.
      CONCLUSIONS: Our results have demonstrated a low occurrence of UTI in antenatally
      diagnosed patients not maintained on antibiotics. We have concluded that
      antibiotic prophylaxis is unlikely to benefit most children with grade 3 or 4
      hydronephrosis secondary to upper tract obstruction.

PMID- 18619655
TI  - Emphysematous pyelonephritis with acute renal failure.
AB  - A 56-year-old woman with obesity and poorly controlled diabetes mellitus
      presented with a two-day history of abdominal fullness and vomiting. No fever,
      flank pain or dysuria was present. On admission, her blood urea nitrogen
      concentration was 74 mg per deciliter and the serum creatinine concentration was
      3.5 mg per deciliter. Laboratory data revealed an elevated white blood cell count
      (11.72 x 10(3)/ml), blood sugar (826 mg/dl), pyuria (WBC 30-50/HPF) and negative
      urine ketone. A plain abdominal radiograph revealed right renal stones and
      localized air accumulation at the left upper abdominal area.

PMID- 18619656
TI  - Dual source computed tomography: a novel technique to determine stone
      composition.
AB  - INTRODUCTION: Dual source computed tomography (CT), a novel technology that
      employs two different x-ray sources, may provide an image resolution that has not
      been possible with conventional single source CT. We tested the ability of dual
      source CT imaging to distinguish calcium oxalate (CaOx) stones from calcium
      phosphate (CaP) stones, and both types of calciferous stones from uric acid (UA)
      stones. METHODS: CaOx, CaP, and UA stones were placed in a tissue phantom and
      imaged with dual source multidetector CT at both 80kV and 140 kV. Hounsfield
      units (HU) of each stone were recorded for the 140 kV and the 80 kV datasets by
      drawing regions of interest by circle, hand-drawing, and using a volume
      calculation method. The differences between, and the ratios of, the HU obtained
      by the two energy sources were compared among the stone groups. RESULTS: Between
      CaOx and CaP stones, HU differences (80kV-140kV difference, hand-drawing
      technique: CaOx = 270.7; CaP = 369.5; UA = 11.45; P = 0.020 for CaOx vs. CaP; P <
      0.001 for CaOx and CaP vs. UA) as well as ratios (140kV:80kV ratio, hand-drawing
      technique: CaOx = 1.44; CaP = 1.51; UA = 1.04; P = 0.001 for CaOx vs. CaP; P <
      0.001 for CaOx and CaP vs. UA) were significantly different. There were no
      significant differences in stone size among the groups. CONCLUSIONS: Dual source
      CT has the ability to distinguish not only between calciferous stones and uric
      acid stones, but also among stones composed of different calcium salts. Further
      studies are warranted to confirm these findings in a clinical setting.

PMID- 18619657
TI  - Patterns of hematuria referral to urologists: does a gender disparity exist?
AB  - OBJECTIVES: To examine the referral patterns of hematuria within a nonprofit
      healthcare organization to determine the factors that influence referral.
      Hematuria continues to be an important sign of urologic disease, including
      urothelial malignancy. An increasing awareness of gender differences in tumor
      stage at bladder cancer presentation has led to speculation about delayed
      referral and diagnosis in women. However, little is known about the referral
      patterns of hematuria and whether gender differences exist. METHODS: The
      insurance records were examined from 926 consecutive adult health plan
      participants (559 men and 367 women) with newly diagnosed hematuria from 1998 to
      2002. The patterns of urologic referral were evaluated. A Cox multivariate
      regression model was used to examine the relationship between urologic referral
      and the relevant variables. RESULTS: Overall, 263 men (47%) and 102 women (28%)
      were referred for urologic evaluation of hematuria, with a median follow-up of 27
      and 26 months, respectively. Referral was initiated by the primary care physician
      in 80% of the cohort. Increased urologic referral was associated with advancing
      age, repeated hematuria, provider type, and male gender. The adjusted hazard
      ratio of male referral was 1.65 (95% confidence interval 1.31-2.08) compared with
      female referral. CONCLUSIONS: Primary care physicians practicing in a managed
      care setting are less likely to refer women for a urologic evaluation of new or
      first recurrent episodes of hematuria than to refer men in all patient age
      categories, except for 40-49 years. This apparent gender disparity could result
      in unequal access of specialty evaluation and could potentially delay the
      diagnosis of important urologic conditions.

PMID- 18619658
TI  - Newborn with klinefelter syndrome and posterior urethral valves.
AB  - We describe the case of a 10-day-old term infant with 47,XXY, in association with
      posterior urethral valves, a right ectopic ureter, a right dysplastic kidney,
      left hydronephrosis, cryptorchidism, and encephalomalacia. The renal anomaly was
      diagnosed prenatally by ultrasonography, and additional evaluation was performed
      after birth. Urinary tract anomalies are uncommon in Klinefelter syndrome.
      Unilateral and bilateral renal agenesis have been described. We describe, to our
      knowledge, the first case of posterior urethral valves, ectopic ureter, and
      encephalomalacia in association with 47,XXY.

PMID- 18619659
TI  - Posttraumatic posterior urethral strictures in children--management and
      intermediate-term follow-up in tertiary care center.
AB  - OBJECTIVES: To evaluate the management and intermediate-term follow-up of
      posttraumatic posterior urethral strictures in children. METHODS: From March 2000
      to November 2006, the surgical records of 28 children (< or = 18 years) who had
      been admitted for treatment of posttraumatic posterior urethral strictures were
      retrospectively reviewed. The patients had been followed up for a median of 36
      months (range 3-58). The cause of trauma, extent of urinary tract injury,
      radiologic examination findings, previous treatment, and its effect on the final
      outcome, treatment complications,, and failures were evaluated. RESULTS: The mean
      age of the patients was 12.1 years (range 5-18) at the injury. The estimated
      radiographic mean stricture length before surgery was 3.41 cm (range 2-6). Of the
      28 patients, 27 were treated with transperineal anastomotic urethroplasty, with a
      success rate of 75%. All treatment failures were at the anastomotic site and
      occurred within the first year of anastomotic urethroplasty. The failed repairs
      (7 cases) were successfully managed endoscopically in 4 patients and by redo
      urethroplasty in 3, for a final success rate of 100%. Of the 28 patients, 15
      (80%) with urethral manipulation before anastomotic urethroplasty had a
      satisfactory result compared with 69.3% of patients without previous surgical
      treatment. The difference was not statistically significant. CONCLUSIONS: Most
      posttraumatic posterior urethral strictures in children can be managed through
      the perineal route. The transpubic approach should be reserved for more complex
      posterior strictures. Previous urethral manipulations did not affect the
      intermediate-term results of anastomotic urethroplasty.

PMID- 18619660
TI  - Harvesting buccal mucosa graft under local infiltration analgesia--mitigating
      need for general anesthesia.
AB  - For buccal mucosal graft urethroplasty, nasal or oral endotracheal intubation
      anesthesia is used for harvesting the graft from the oral cavity. A technique of
      graft harvesting under local anesthesia using 2% lidocaine solution with
      adrenaline (1:200,000) is described. This method requires a cooperative patient
      but saves the morbidity of general anesthesia.

PMID- 18619661
TI  - Trocar site spigelian-type hernia after robot-assisted laparoscopic
      prostatectomy.
AB  - A 71-year-old man with unilateral, Gleason score 7 (3 + 4), clinical Stage T1c
      prostate adenocarcinoma underwent bilateral nerve-sparing robot-assisted
      laparoscopic prostatectomy. On postoperative day 13, he developed a small bowel
      obstruction owing to incarceration of a spigelian hernia in the right lower
      quadrant 8-mm trocar site. Surgical repair required small bowel resection and
      primary enteroenterostomy.

PMID- 18619662
TI  - Protein kinase C inhibitor Go6976 augments caffeine-induced reversal of
      chemoresistance to cis-diamminedichloroplatinum-II (CDDP) in a human ovarian
      cancer model.
AB  - OBJECTIVES: Novel strategies for the treatment of chemoresistant ovarian cancer
      are needed. Caffeine and related compounds have been shown to over-ride G2/M
      arrest in ovarian cancer cells, increasing toxicity to chemotherapy. Newer
      compounds have been developed which may have the same effect as and exhibit
      synergism with caffeine, allowing the use of lower doses. METHODS: We
      investigated the effects of caffeine and Go6976 in the presence of CDDP in the
      SKOV3 and A2780 cell lines using proliferation, cell-cycle analysis, apoptosis,
      and AKT expression. RESULTS: Proliferation of cancer cells was decreased in a
      dose-dependent manner with caffeine and CDDP, but doses of caffeine required for
      significant inhibition were higher than that achievable in patients. Go6976, a
      global PKC inhibitor with G2/M over-ride capability similar to caffeine, when
      combined with caffeine and CDDP at doses below that required for cell-cycle over
      ride produced the growth inhibitory effects of a ten-fold higher caffeine
      concentration in both cell lines. CDDP induced G2/M arrest was significantly
      abrogated by caffeine but not by Go6976 alone and no additional effect was seen
      on G2/M over-ride by the addition of Go6976 to caffeine. Addition of Go6976 to
      caffeine and CDDP did increase apoptosis but without altering phospho-AKT.
      CONCLUSIONS: Go6976, when added to caffeine at doses below that required for cell
      cycle over-ride, augments caffeine in overcoming CDDP resistance in this
      experimental system. G2/M over-ride is not the mechanism underlying the
      inhibition of proliferation. An AKT-independent apoptotic mechanism may be
      responsible.

PMID- 18619663
TI  - The elite athlete: yes, with allergy we can.

PMID- 18619664
TI  - Advantages and disadvantages of accelerated immunotherapy schedules.

PMID- 18619665
TI  - The role of wheat omega-5 gliadin IgE antibodies as a diagnostic tool for wheat
      allergy in childhood.

PMID- 18619666
TI  - Advances in asthma and allergy genetics in 2007.
AB  - This review discusses the main advances in the genetics of asthma and allergy
      published in the Journal in 2007. The association studies discussed herein
      addressed 3 main topics: the effect of the environment and gene-environment
      interactions on asthma/allergy susceptibility, the contribution of T(H)2 immunity
      gene variants to allergic inflammation, and the role of filaggrin mutations in
      atopic dermatitis and associated phenotypes. Other articles revealed novel,
      potentially important candidate genes or confirmed known ones. Collectively, the
      works published in 2007 reiterate that allergy and asthma are typical complex
      diseases; that is, they are disorders in which intricate interactions among
      environmental and genetic factors modify disease susceptibility by altering the
      fundamental structural and functional properties of target organs at critical
      developmental windows.

PMID- 18619668
TI  - Task-dependent semantic interference in language production: an fMRI study.
AB  - We used fMRI to investigate competition during language production in two word
      production tasks: object naming and color naming of achromatic line drawings.
      Generally, fMRI activation was higher for color naming. The line drawings were
      followed by a word (the distractor word) that referred to either the object, a
      related object, or an unrelated object. The effect of the distractor word on the
      BOLD response was qualitatively different for the two tasks. The activation
      pattern suggests two different kinds of competition during lexical retrieval: (1)
      Task-relevant responses (e.g., red in color naming) compete with task-irrelevant
      responses (i.e., the object's name). This competition effect was dominant in
      prefrontal cortex. (2) Multiple task-relevant responses (i.e., target word and
      distractor word) compete for selection. This competition effect was dominant in
      ventral temporal cortex. This study provides further evidence for the distinct
      roles of frontal and temporal cortex in language production, while highlighting
      the effects of competition, albeit from different sources, in both regions.

PMID- 18619670
TI  - Innovations in Rwanda's health system: looking to the future.
AB  - Rwanda is making substantial progress towards improvement of health and is
      working towards achievement of the Millennium Development Goals, which is a
      challenging task because the country has had genocide in 1994, has few natural
      resources, is landlocked, and has high population growth. Like many impoverished
      sub-Saharan countries, Rwanda's health system has had an uncoordinated plethora
      of donors, shortage of health staff, inequity of access, and poor quality of care
      in health facilities. This report describes three health system developments
      introduced by the Rwandan government that are improving these barriers to care
      ie, the coordination of donors and external aid with government policy, and
      monitoring the effectiveness of aid; a country-wide independent community health
      insurance scheme; and the introduction of a performance-based pay initiative. If
      these innovations are successful, they might be of interest to other sub-Saharan
      countries. However, Rwanda still does not have sufficient financial resources for
      health and will need additional external aid for some time to attain the
      Millennium Development Goals.

PMID- 18619671
TI  - Biodegradable biocomposite films based on whey protein and zein: barrier,
      mechanical properties and AFM analysis.
AB  - Whey and zein protein are byproducts of the food industries and have good film
      making properties. Single and laminated films were produced from zein protein and
      whey protein and their film properties were studied. Glycerol and olive oil were
      used as plasticizer for the single and laminated films. The laminated films
      exhibited higher ultimate tensile strength (UTS) than the single whey protein
      films (260% and 200% in the whey-zein-glycerol and whey-zein-olive oil films,
      respectively). The UTS of the whey protein films increased 2-3-fold after
      lamination. The laminated films showed higher barrier properties than the single
      whey protein films (180% in the whey protein-zein-glycerol films and 200% in the
      whey protein-zein-olive oil films in comparison to single whey protein films) and
      lower than the single zein films.

PMID- 18619669
TI  - Progress in matrix metalloproteinase research.
AB  - Matrix metalloproteinases (MMPs) are now acknowledged as key players in the
      regulation of both cell-cell and cell-extracellular matrix interactions. They are
      involved in modifying matrix structure, growth factor availability and the
      function of cell surface signalling systems, with consequent effects on cellular
      differentiation, proliferation and apoptosis. They play central roles in
      morphogenesis, wound healing, tissue repair and remodelling in response to injury
      and in the progression of diseases such as arthritis, cancer and cardiovascular
      disease. Because of their wide spectrum of activities and expression sites, the
      elucidation of their potential as drug targets in disease or as important
      features of the repair process will be dependent upon careful analysis of their
      role in different cellular locations and at different disease stages. Novel
      approaches to the specific regulation of individual MMPs in different contexts
      are also being developed.

PMID- 18619672
TI  - Placentomegaly in paternal uniparental disomy for human chromosome 14.

PMID- 18619674
TI  - Disruption of ERK signalling in Biomphalaria glabrata defence cells by
      Schistosoma mansoni: implications for parasite survival in the snail host.
AB  - Biomphalaria glabrata is an intermediate snail host for the human blood fluke
      Schistosoma mansoni. To survive in B. glabrata, S. mansoni must suppress the
      snail's haemocyte-mediated defence response; the molecular mechanisms by which
      this is achieved remain largely unknown. We report here that S. mansoni excretory
      secretory products (ESPs) attenuate phosphorylation of extracellular signal
      regulated kinase (ERK) in haemocytes from a B. glabrata strain susceptible to S.
      mansoni. Whole S. mansoni sporocysts also impair ERK signalling in these cells.
      In striking contrast, ERK signalling in haemocytes from a B. glabrata strain
      refractory to schistosome infection is unaffected by ESPs or sporocysts. Effects
      of ESPs on ERK are similar in the presence or absence of snail plasma, thus ESPs
      seem to affect haemocytes directly. These findings reveal novel schistosome
      interference mechanisms; as ERK regulates various haemocyte defence reactions, we
      propose that disruption of ERK signalling in haemocytes facilitates S. mansoni
      survival within susceptible B. glabrata.

PMID- 18619673
TI  - Differential activation of enkephalin, galanin, somatostatin, NPY, and VIP
      neuropeptide production by stimulators of protein kinases A and C in
      neuroendocrine chromaffin cells.
AB  - Neuropeptides function as peptide neurotransmitters and hormones to mediate cell
      cell communication. The goal of this study was to understand how different
      neuropeptides may be similarly or differentially regulated by protein kinase A
      (PKA) and protein kinase C (PKC) intracellular signaling mechanisms. Therefore,
      this study compared the differential effects of treating neuroendocrine
      chromaffin cells with stimulators of PKA and PKC on the production of the
      neuropeptides (Met)enkephalin, galanin, somatostatin, NPY, and VIP.
      Significantly, selective increases in production of these neuropeptides were
      observed by forskolin or phorbol myristate acetate (PMA) which stimulate PKA and
      PKC mechanisms, respectively. (Met)enkephalin production was stimulated by up to
      2-fold by forskolin treatment, but not by PMA. In contrast, PMA treatment (but
      not forskolin) resulted in a 2-fold increase in production of galanin and
      somatostatin, and a 3-fold increase in NPY production. Notably, VIP production
      was highly stimulated by forskolin and PMA, with increases of 3-fold and 10-15
      fold, respectively. Differences in elevated neuropeptides occurred in cell
      extracts compared to secretion media, which consisted of (i) increased NPY
      primarily in secretion media, (ii) increased (Met)enkephalin and somatostatin in
      secretion media (not cell extracts), and (iii) increased galanin and VIP in both
      cell extracts and secretion media. Involvement of PKA or PKC for forskolin or PMA
      regulation of neuropeptide biosynthesis, respectively, was confirmed with direct
      inhibitors of PKA and PKC. The selective activation of neuropeptide production by
      forskolin and PMA demonstrates that PKA and PKC pathways are involved in the
      differential regulation of neuropeptide production.

PMID- 18619675
TI  - Analysis of behavioral constraints and the neuroanatomy of fear to the predator
      odor trimethylthiazoline: a model for animal phobias.
AB  - Specific phobias, including animal phobias, are the most common anxiety
      disorders, and have a strong innate and genetic component. Research on the
      neurobiology and environmental constraints of innate fear of predators in rodents
      may be useful in elucidating mechanisms of animal phobias in humans. The present
      article reviews research on innate fear in rats to trimethylthiazoline (TMT), an
      odor originally isolated from fox feces. TMT induces unconditioned freezing and
      other defensive responses that are regulated by the dose of TMT and the shape of
      the testing environment. Contextual conditioning induced by TMT occurs, but is
      constrained by the environment. Lesion studies indicate the amygdala circuitry
      subserving fear conditioning is not necessary for unconditioned fear to TMT.
      Additionally, a medial hypothalamic defensive circuit also appears not necessary
      for unconditioned freezing to TMT, whereas circuits that include the medial
      nucleus of the amygdala and the bed nucleus of the stria terminalis are
      essential. The importance of these findings of innate predator odor fear in
      rodents to animal phobias in humans is discussed.

PMID- 18619676
TI  - Defect in TCR-CD3zeta signaling mediates T cell hypo-responsiveness in mesenteric
      lymph node.
AB  - Mesenteric lymph node (MLN) in gut-associated lymphoid tissue plays obligatory
      roles in the induction of oral tolerance and ignorance to commensals. However,
      little is known about its immunological characteristics. In this study, we
      investigated the hypo-responsiveness of MLN CD4(+) T cells, comparing them with
      spleen CD4(+) T cells. MLN CD4(+) T cells were hypo-proliferative and expressed
      low levels of Th1-type cytokines in response to antigen or CD3/T cell receptor
      (TCR) stimulation. The hypo-responsiveness of MLN CD4(+) T cells is linked
      neither with changes in the regulatory T cell population (CD4(+)CD25(+),
      CD4(+)Foxp3(+)) nor the apoptotic population. Rather, MLN CD4(+) T cells showed
      deformity of T cell:APC conjugation and reduced expression of TCR signaling
      molecules such as CD3zeta, PLC-gamma1, PKC-theta, Zap70, with reduced
      phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs). Among
      the alterations in TCR signaling molecules, defective CD3zeta expression is the
      most evident, and reversal of the anergic state by CD3/CD28 costimulation
      restored CD3zeta expression levels. Collectively, we suggest that reduced CD3zeta
      expression and defects in TCR signaling mediate the anergy state of MLN CD4(+) T
      cells, which play a critical role in maintenance of mucosal tolerance in gut
      associated lymphoid tissue.

PMID- 18619677
TI  - Suicide in Italian children and adolescents.
AB  - BACKGROUND: Data and statistics on suicide mortality in several countries have
      been published and discussed over the last few decades but gaps in knowledge are
      present in the epidemiology of suicide among Italian youths. METHODS: Suicide
      mortality data for the years 1973-2002 were obtained from the Italian Central
      Institute of Statistics (ISTAT). Age-standardized mortality rates were calculated
      and examined for trends over time. RESULTS: During the last 3 decades the Italian
      population's overall suicide rate increased slightly from 67.8 per million in
      1973 to 76.7 in 2002. Suicide rates were higher in males than females (2.8:1) and
      in Northern compared to Southern Italy. Suicide rates increased with age from 4.4
      per million for children 10-14 years old to 25.8 (15-19 years) and 95.6 (> or =
      20 years). The major increase over time was observed for 15-19 year old males.
      LIMITATIONS: Routine suicide mortality data have several weaknesses; these are
      especially, related to the level of accuracy in the certification of violent
      causes of death. CONCLUSION: A national research programme to study suicidal
      behaviour and risk factors in children and adolescents is essential. The
      permanent monitoring of the situation, exploring gender and interpersonal issues
      with the aim to plan protective initiatives in an appropriate manner, is also
      fundamental.

PMID- 18619678
TI  - Expression profile of toll like receptors in a range of water buffalo tissues
      (Bubalus bubalis).
AB  - The present study was carried out to determine the expression profile of toll
      like receptors (TLRs) 1-10 in buffalo peripheral blood mononuclear cells (PBMNC),
      neutrophils, spleen, liver, lung, heart, kidney, ovary and uterus using reverse
      transcriptase polymerase chain reaction (RT-PCR) with bovine TLR-specific primers
      The buffalo TLR partial nucleotide sequences had 95-98% nucleotide homology with
      bovine TLR sequences available in the GenBank. PBMNC expressed all TLRs except
      TLR1 and neutrophils expressed all TLRs except TLR3. Expression of all TLRs was
      observed in spleen, lung and liver tissues. Wide range of TLR mRNA expression was
      observed in heart, which lacked the expression of only TLR10. Among the tissues
      analyzed kidneys had the least repertoire of TLR expression. The kidney tissue
      revealed mRNA expression of only TLR2, TLR5, TLR7 and TLR9. Among the
      reproductive tissues analyzed, uterus expressed a wide range of TLRs such as 2,
      5, 7, 8, 9 and 10 while ovary expressed all TLRs except TLR1 indicating their
      immuno competence.

PMID- 18619679
TI  - Disproportionally strong increase of B cells in inflammatory cerebrospinal fluid
      of dogs with Steroid-responsive Meningitis-Arteritis.
AB  - Steroid-responsive Meningitis-Arteritis (SRMA) is a systemic inflammatory disease
      of juvenile to young adult dogs with a relapsing course and most prominent
      manifestation in the cervical meninges. Immunophenotyping and flow cytometric
      measurement of lymphocytes in peripheral blood (PB) and CSF was performed in the
      acute phase of SRMA (n=12) and during glucocorticosteroid treatment (n=10).
      Values were compared to those from dogs with other neurologic diseases (n=63) and
      healthy individuals (n=7). Dogs with SRMA had high CD4:CD8alpha ratios in PB and
      low T:B cell ratios in PB and CSF suggesting that a T(H)2-mediated immune
      response occurs. The T:B cell ratio in CSF was markedly lower than that in PB
      indicating that either a selective recruitment of B cells or, alternatively,
      their strong intrathecal proliferation takes place. SRMA appears to be a valuable
      animal model for the investigation of compartmentalization of immune responses
      and for studies on differences in local central nervous system and systemic
      immune responses.

PMID- 18619680
TI  - Atypical thyroglossal duct anomalies.
AB  - OBJECTIVE: Thyroglossal duct (TD) anomalies are generally considered to be a
      distinct clinical entity. However occasional cases do not conform to the standard
      picture and are complex. This study aimed to scrutinise consecutive cases of TD
      anomaly managed surgically over 7 years at a tertiary teaching hospital and
      analyse those with atypical features. METHODS: This is a retrospective study of
      62 children managed for a clinical diagnosis of TD anomaly from 1998 to 2005.
      Their medical records were reviewed for clinical presentation, investigations,
      operative findings, histopathology, management and outcome. After a clinical
      diagnosis, they had individualized investigations (USG, MRI, radioiodine scan,
      FNA) prior to the Sistrunk operation. RESULTS: 5/62 cases had atypical features.
      2/5 were adolescents with a short history while 3 were below 5 years of age with
      onset since infancy. 4/5 were females. 1/5 had a Sistrunk operation earlier, 2/5
      had a redo surgery prior to cure. 3/5 had a grossly identifiable tract at
      surgery, one with a midline course and two deviating laterally to open at the
      left pharyngeal wall. The final histological diagnosis was a mixed thyroglossal
      dermoid cyst (case 1), TD anomalies with aberrant pharyngeal communication (cases
      2 and 3), isthmic thyroglossal 'cold' cyst (case 4), and a tuberculous cyst (case
      5). Postoperatively, Cases 2 and 3 had wound infections that were managed
      conservatively while case 5 developed an incisional sinus that healed after a
      month of anti-tuberculous chemotherapy. Cases 1 and 4 had an uneventful recovery.
      At an average f/u of 2 years, all are asymptomatic and well. CONCLUSIONS: 5-10%
      of apparent TD anomalies may present with atypical clinicopathologic
      characteristics. Atypical cases and late presentations may warrant additional
      investigations to establish the diagnosis and tailor management.

PMID- 18619681
TI  - A simple and rapid immunochromatographic strip test for detecting antibody to
      porcine reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome is rapidly gaining worldwide
      importance as one of the most economically significant diseases of swine. The
      antibody of Porcine reproductive and respiratory syndrome virus (PRRSV) is
      detected currently by the combined use of an enzyme-linked immunosorbent assay,
      serum neutralization test, immunoperoxidase monolayer assay, indirect
      immunofluorescent antibody test. These methods are time-consuming and require
      specialized equipment operated by trained technicians. The purpose of this study
      was to evaluate a simple strip assay (based on a chromatographic and immunogold
      system) for specific detection of PRRSV antibody in swine sera. This
      "immunochromatographic strip" test uses Escherichia coli-expressed viral
      recombinant membrane protein antigen in combination with recombinant nucleocapsid
      protein as capture protein for detecting antibodies against PRRSV. In this study,
      the performance of this assay was evaluated with sera from both clinical samples
      and experimentally infected piglets. Detection by immunochromatographic strip
      test was compared with detection by a standard, available commercially, indirect
      enzyme-linked immunosorbent assay and an immunoperoxidase monolayer assay. The
      immunochromatographic test strip detected antibodies in sera known to contain
      antibodies to PRRSV in 95.7% sensitivity of samples from pigs infected
      experimentally and 98.6% sensitivity of clinical serum samples. For sera that did
      not contain antibodies to PRRSV, the specificity was 97.8% and 98.2% for clinical
      and experimental serum samples, respectively.

PMID- 18619682
TI  - Decoupling of cadmium biokinetics and metallothionein turnover in a marine
      polychaete after metal exposure.
AB  - This study investigated the kinetics of Cd bioaccumulation, detoxification,
      subcellular distribution, and efflux in the nereid polychaete Perinereis
      aibuhitensis after Cd pre-exposure. Cd pre-exposure increased the Cd body burden
      in the worms, but did not affect the overall Cd uptake and efflux rates and
      metallothionein-like protein (MTLP) concentrations. During short-term exposure to
      dissolved Cd, Cd in the cytosolic fraction increased after Cd pre-exposure, and
      this fraction also increased during the Cd efflux period, indicating that the
      insoluble fraction of Cd was presumably lost at a faster rate than the loss of
      cytosolic Cd. Even though the MTLP concentration remained comparable after Cd pre
      exposure, both the MTLP synthesis rate and the degradation rate increased, thus
      leading to a high MTLP turnover in the Cd-exposed worms. However, Cd uptake and
      efflux into different protein size fractions did not follow the patterns of MTLP
      synthesis and degradation, strongly suggesting that Cd kinetics is decoupled from
      the MTLP kinetics in the worms. Our study adds to an increasing body of evidence
      on the complicated relationship between metal biokinetics and MTLP kinetics in
      different groups of marine invertebrates which have strong contrasts in their
      metal handling strategies.

PMID- 18619683
TI  - In vitro characterization of cadmium and zinc uptake via the gastro-intestinal
      tract of the rainbow trout (Oncorhynchus mykiss): Interactive effects and the
      influence of calcium.
AB  - An in vitro gut sac technique was employed to study whether Cd and Zn uptake
      mechanisms in the gastro-intestinal tract of the rainbow trout are similar to
      those at the gills, where both metals are taken up via the Ca transport pathway.
      Metal accumulation in surface mucus, in the mucosal epithelium, and transport
      into the blood space were assayed using radiolabelled Cd or Zn concentrations of
      50micromolL(-1) in the luminal (internal) saline. Elevated luminal Ca (10 or
      100mmolL(-1)versus 1mmolL(-1)) reduced Cd uptake into all three phases by
      approximately 60% in the stomach, but had no effect in the anterior, mid, or
      posterior intestine. This finding is in accordance with recent in vivo evidence
      that Ca is taken up mainly via the stomach, and that high [Ca] diets inhibit Cd
      accumulation from the food specifically in this section of the tract. In
      contrast, 10mmolL(-1) luminal Ca had no effect on Zn transport in any section,
      whereas 100mmolL(-1) Ca stimulated Zn uptake, by approximately threefold, into
      all three phases in the stomach only. There was no influence of elevated luminal
      Zn (10mmolL(-1)) on Cd uptake in the stomach or anterior intestine, or of high Cd
      (10mmolL(-1)) on Zn uptake in these sections. However, high [Zn] stimulated Cd
      transport into the blood space but inhibited accumulation in the mucosal
      epithelium and/or mucus-binding in the mid and posterior intestine, whereas high
      [Cd] exerted a reciprocal effect in the mid-intestine only. We conclude that Cd
      uptake occurs via an important Ca-sensitive mechanism in the stomach which is
      different from that at the gills, while Cd transport mechanisms in the intestine
      are not directly Ca-sensitive. Zn uptake does not appear to involve Ca uptake
      pathways, in contrast to the gills. These results are discussed in the context of
      other possible Cd and Zn transport pathways, and the emerging role of the stomach
      as an organ of divalent metal uptake.

PMID- 18619684
TI  - Effects of hypertension on balance assessed by computerized posturography in the
      elderly.
AB  - Unsteadiness, dizziness and vertigo occur more frequently in hypertensive
      subjects, compared to the normal ones. This study evaluated the influence of
      hypertension on balance tests, performed on posturographic platform. The study
      pool consisted of 112 persons aged 65 and older (65 hypertensives), their mean
      age was 72.9+/-0.5, scored on the Mini Mental State Examination (MMSE) greater
      than 24, were able to perform self-care activities, to walk independently for at
      least 400 m and were free from major diseases. Subjective dizziness and vertigo
      were assessed by means of Sickness-Impact-Profile-Questionnaire (SIPQ). The
      static posturographic tests were performed on a vertical force platform, from
      which the center of foot pressure (COP) positions and displacements were
      recorded. In balance tests three standardized positions were utilized: feet 30
      degrees apart, semitandem and tandem. Subjects with hypertension complained more
      frequently dizziness and vertigo (41.5% vs. 21.3%). The track-length and COP
      velocity were associated with age in all the balance tests. In semitandem and
      tandem positions, the medio-lateral sway distance significantly increased in
      elderly subjects compared to young controls. No difference, however, was found in
      balance tests between normotensive and hypertensive subjects. Those with
      uncomplicated hypertension compared with normo-tensive subjects, although
      complaining more frequently symptoms of postural instability, did not show worse
      performances in static posturographic tests.

PMID- 18619685
TI  - Apolipoprotein E (APOE) and lipoprotein lipase (LPL) gene variants and carotid
      atherosclerotic lesions in the oldest old: a population-based autopsy study.
AB  - We investigated the association between histologically defined atherosclerotic
      lesions in the carotid arteries and the genetic variants of APOE and LPL in a
      population-based sample of Finns aged 85 or over. Post-mortem analysis of carotid
      arteries was performed in 240 subjects. Atherosclerotic lesions were categorized
      according to the modified American Heart Association criteria, and classified
      into four different categories: pathological intimal thickening (PIT), fibrous
      cap atheromas (FCA), calcified lesions (CL), and atherosclerotic burden (AB) (a
      combination of the other three categories). APOE epsilon4 genetic variant was
      associated with PIT (p=0.018) and AB (p=0.006) in the carotid arteries, and its
      effect was independent of the serum lipid levels. The genetic variant LPL
      Ser447Ter was protective against FCA (p=0.031) and AB (p=0.012), while APOE
      epsilon2 was protective against FCA (p=0.035). Our results suggest that the APOE
      epsilon4, epsilon2 and LPL Ser447Ter variants may have different roles in the
      atherosclerotic process and their effects are seen even in the oldest old
      population.

PMID- 18619686
TI  - The use of B-type natriuretic peptide in the management of patients with atrial
      fibrillation and dyspnea.
AB  - The utility of B-type natriuretic peptide (BNP) testing in patients with atrial
      fibrillation (AF) is poorly defined. We analyzed patients (n=452) included in the
      BNP for Acute Shortness of Breath Evaluation (BASEL) study. Patients were
      randomly assigned to a diagnostic strategy with or without the use of BNP. Ninety
      nine patients presented with AF (n=48 BNP group; n=51 control group). Although
      comparable with respect to gender and cardiopulmonary comorbidity, patients with
      AF were older and more often had heart failure as the cause of dyspnea. In
      addition, patients with AF had higher in-hospital mortality (13% versus 6%,
      P=0.012). The use of BNP significantly reduced time to discharge (BNP group
      median 8 days [1-16] versus 12 days [IQR 4-21] control group; P=0.046) in
      patients with AF. Initial total treatment costs (median) were $4239 [769-7422] in
      the BNP group and $5940 [4024-10848] in the control group (P=0.041). These
      benefits were maintained after 90 days: patients in the BNP group had spent fewer
      days in hospital (10 days [2-21] versus 15 days [IQR 9-27]; P=0.022) and induced
      lower total treatment costs ($4790 [1260-9387] versus $7179 [4311-13173];
      P=0.016). In conclusion, the use of BNP seems to improve the management of
      patients with AF presenting with dyspnea.

PMID- 18619687
TI  - Paediatric radiofrequency ablation experience at a Venezuelan cardiology
      facility.
AB  - Radiofrequency (RF) ablation is a curative treatment for many different types of
      cardiac arrhythmias but its application has been more limited in the paediatric
      population. We here describe RF paediatric ablation experience at a 400-bed
      University Hospital in a western Venezuelan province and compare it with the
      results reported in other countries. METHODS: One hundred and fifty five patients
      under 18 years of age who where submitted to RF ablation between 1994 and 2007
      were included. The patients were 12.8+/-3.4 year-old (rank: 3-17 years); 59% were
      female. Nine patients were submitted to more than one procedure. AV nodal re
      entrant tachycardia and atrio-ventricular re-entrant tachycardias mediated by
      accessory pathways made up 83% of the ablations. The overall success rate was
      91.5%. In the AV nodal re-entrant tachycardia and atrial flutter, success rate
      almost reached 100%. Ablation was successful in 93% of the patients with the
      Wolff-Parkinson-White syndrome. The overall complication rate was 5% with 0.6% of
      major complications and 0% death rate. The results were comparable to those
      recently reported by the cooperative paediatric ablation registry in the United
      States of America and by a large hospital in Taiwan. CONCLUSION: RF ablation is a
      curative therapy with a high success rate and very low complication rates in the
      paediatric population at the Cardiovascular Research Institute of the University
      Hospital of The Andes in Venezuela.

PMID- 18619688
TI  - Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a
      rat model of heart failure.
AB  - BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are
      very complicated and still unclear. The aim of this study was to investigate
      whether autophagy was involved in the progression of heart failure induced by
      adriamycin, so that we can develop a novel treatment strategy for heart failure.
      METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a
      heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were
      isolated from Sprague-Dawley rat hearts and randomly divided into controls, an
      adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then
      examined the morphology, expression of beclin 1 gene, mitochondrial permeability
      transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell
      viability, mitochondrial membrane potential changes and counted autophagic
      vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of
      autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an
      animal model. RESULTS: 3MA significantly improved cardiac function and reduced
      mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic
      vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin
      induced failing heart and inhibited the formation of autophagic vacuoles.
      CONCLUSION: Autophagic cardiomyocyte death plays an important role in the
      pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury
      may be involved in the progression of heart failure caused by adriamycin via the
      autophagy pathway.

PMID- 18619689
TI  - Financial strain predicts recurrent events among women with coronary artery
      disease.
AB  - BACKGROUND: Although a number of epidemiological studies have found an
      association between socioeconomic status (SES) indices such as income and
      education and coronary morbidity and mortality, few have looked at health
      consequences arising from actually experiencing financial shortcomings. The
      objective of the present study was to examine whether financial strain predicts
      recurrent coronary artery disease (CAD) events among women with established CAD.
      METHODS: Two hundred two women (mean age 62+/-9 years) hospitalized for an acute
      coronary event were followed over a period of 3.5 years. Demographic,
      socioeconomic, lifestyle-related, psychosocial and biological characteristics
      were obtained by means of questionnaires and clinical examination. Data on
      recurrent cardiac events were collected from the Swedish discharge and death
      registers. RESULTS: Women experiencing financial strain over the past year had an
      increased risk for recurrent events, i.e. the combination of all-cause mortality,
      new acute myocardial infarction and unstable angina pectoris during the follow-up
      with an unadjusted hazard ratio (HR) of 3.2 (95% CI 1.6-6.6), and a HR of 2.76
      (95% CI 1.02-7.50) after controlling for education, household income, age,
      cohabiting status, inclusion diagnosis and rehabilitation therapy. Adjustment for
      potential mediators, i.e. psychosocial factors, lipids, diabetes mellitus,
      smoking, body-mass index, blood pressure, physical activity, alcohol consumption,
      participation in other cardiac rehabilitation programs did not alter the results
      significantly. CONCLUSIONS: Financial strain was a predictor for recurrent events
      among women with CAD, independently of commonly used SES indicators such as
      education and household income. Future studies will have to explore the mechanism
      behind this association.

PMID- 18619690
TI  - Coronary artery dilation after Kawasaki disease for children within the normal
      range.
AB  - BACKGROUND: Kawasaki disease is an acute, self-limited vasculitis of unknown
      etiology. Coronary artery involvement is the predominant complication, ranging
      from no involvement to dilation through to aneurysm formation. We sought to
      determine trends over time and associated factors for normalized coronary artery
      dimensions for patients with acute KD. METHODS: Clinical data and
      echocardiographic studies were reviewed for patients with acute Kawasaki disease
      over a 3 year period having standardized assessments and management strategies.
      Patients with echocardiograms from the initial, 6-8 week, and 1 year post
      Kawasaki disease assessments were included. Coronary artery measurements were
      normalized for body surface area. A mixed linear regression analysis for repeated
      measures was used to determine trends over time. RESULTS: We included 176
      patients. Based on the Japanese Ministry of Health measurement criteria 11% of
      patients were classified as having coronary artery abnormalities. Normalized
      initial measurements showed Z-scores greater than +2 for 23% of patients for any
      of the coronary artery branches. Particularly for initial measurements, Japanese
      Ministry of Health measurement criteria underestimated the prevalence of
      abnormalities defined by Z-scores. Time trends were noted, such that Z-scores
      decreased from initial values in a logarithmic manner, mostly in the first 2 to 3
      months. Greater than 50% of patients with initial Z-scores within the normal
      range showed a decrease over time, suggesting previously unrecognized dilation.
      CONCLUSION: A longitudinal assessment of normalized coronary artery measurements
      may identify further patients with subtle coronary artery abnormalities after
      acute Kawasaki disease.

PMID- 18619691
TI  - Progress in the management of ST-segment elevation myocardial infarction during
      economic transition in Poland between 1992 and 2006.
AB  - Implementation of new therapeutic strategies is intended to decrease morbidity
      and mortality in patients with acute coronary syndromes (ACS). The aim of this
      study is to evaluate progress in the treatment of ST-segment elevation myocardial
      infarction (STEMI) in 1992-2006 based on data from Polish National ACS Registry.
      A total of 881 STEMI patients in 1992-1996 and 889 in 2005-2006 were enrolled.
      The use of reperfusion therapy resulted in marked reduction in in-hospital and
      post-discharge mortality with the best results achieved in the invasive arm. Low
      invasive approach rate in high-risk patients resulted in no reduction in global
      mortality.

PMID- 18619692
TI  - Quantification of aortic valve area with ECG-gated multi-detector spiral computed
      tomography in patients with aortic stenosis and comparison of two image analysis
      methods.
AB  - Thirty-three consecutive patients with aortic stenosis underwent a 16-row spiral
      CT scan. Aortic valve planimetry was performed using two methods: double-oblique
      reformation (DO) and 2D-curved multiplanar reconstruction using advanced vessel
      analysis software (VA). The mean aortic valve area determined by transthoracic
      echocardiography was 0.88+/-0.34 [0.53-1.88] and did not differ significantly
      from that determined by CT (DO): 0.87+/-0.38 [0.42-1.93] (p=0.75) or CT (VA):
      0.87+/-0.38 [0.44-2.00] (p=0.69). This study demonstrates that 16-row spiral CT
      scan is a feasible, accurate and reproducible method for aortic valve planimetry
      in patients with aortic stenosis. Both methods show similar accuracy but the VA
      method takes slightly longer.

PMID- 18619693
TI  - Treatment and outcome in acute myocardial infarction in a community in relation
      to gender.
AB  - AIM: To describe treatment and outcome in all patients in a community with acute
      myocardial infarction (AMI) in relation to gender. METHODS: All patients
      discharged from hospital between 2001 and 2002 in Goteborg, Sweden, with a
      diagnosis of AMI underwent a survey to find possible gender differences. All p
      values are age adjusted. RESULTS: Among 1423 admissions, women comprised 41% and
      were older than men (mean 79 versus mean 72 years). Women were admitted to a
      coronary care unit less frequently than men (49% versus 67%; p=0.005). Women
      underwent coronary angiography less frequently (21% versus 40%; p=0.02).
      Percutaneous coronary intervention (PCI) was performed in 10% of the women and
      18% of the men (p=0.36). Coronary artery bypass grafting (CABG) was performed in
      2% of the women and in 9% of the men (p<0.0001). Female gender was associated
      with a lower risk of reinfarction during first year after hospital discharge (12%
      versus 16%; p=0.003). The cumulative three-year mortality was 49% in women and
      41% in men. However, when adjusting for age, admittance to CCU, coronary
      angiography and coronary revascularisation, risk of death during 3 years was
      lower in women than men (odds ratio 0.72; 95% confidence interval 0.60-0.85;
      p=0.0001). CONCLUSION: In the community of Goteborg women (mean age 79 years)
      with AMI are prioritised differently than men (mean age 72 years), prior to
      admission to a CCU. This results in a less invasive strategy in women,
      particularly with regard to CABG. When adjusting for difference in age,
      admittance to CCU and coronary revascularisation female gender was associated
      with a low risk of death during the subsequent 3 years.

PMID- 18619694
TI  - Bluetongue in Europe and the Mediterranean Basin: history of occurrence prior to
      2006.
AB  - Bluetongue virus (BTV) exists around the world in a broad band covering much of
      the Americas, Africa, southern Asia and northern Australia. Historically, it also
      occasionally occurred in the southern fringes of Europe. It is considered to be
      one of the most important diseases of domestic livestock. Recently BTV has
      extended its range northwards into areas of Europe never before affected and has
      persisted in many of these locations causing the greatest epizootic of bluetongue
      (BT), the disease caused by BTV, on record. Indeed, the most recent outbreaks of
      BT in Europe are further north than this virus has ever previously occurred
      anywhere in the world. The reasons for this dramatic change in BT epidemiology
      are complex but are linked to recent extensions in the distribution of its major
      vector, Culicoides imicola, to the involvement of novel Culicoides vector(s) and
      to on-going climate-change. This paper investigates these recent outbreaks in the
      European theatre, up to the beginning of 2006, highlights prospects for the
      future and sets the scene for the following papers in this special issue.

PMID- 18619695
TI  - Cost-effectiveness analysis and innovation.
AB  - While cost-effectiveness (CE) analysis has provided a guide to allocating often
      scarce resources spent on medical technologies, less emphasis has been placed on
      the effect of such criteria on the behavior of innovators who make health care
      technologies available in the first place. A better understanding of the link
      between innovation and cost-effectiveness analysis is particularly important
      given the large role of technological change in the growth in health care
      spending and the growing interest of explicit use of CE thresholds in leading
      technology adoption in several Westernized countries. We analyze CE analysis in a
      standard market context, and stress that a technology's cost-effectiveness is
      closely related to the consumer surplus it generates. Improved CE therefore often
      clashes with interventions to stimulate producer surplus, such as patents. We
      derive the inconsistency between technology adoption based on CE analysis and
      economic efficiency. Indeed, static efficiency, dynamic efficiency, and improved
      patient health may all be induced by the cost-effectiveness of the technology
      being at its worst level. As producer appropriation of the social surplus of an
      innovation is central to the dynamic efficiency that should guide CE adoption
      criteria, we exemplify how appropriation can be inferred from existing CE
      estimates. For an illustrative sample of technologies considered, we find that
      the median technology has an appropriation of about 15%. To the extent that such
      incentives are deemed either too low or too high compared to dynamically
      efficient levels, CE thresholds may be appropriately raised or lowered to improve
      dynamic efficiency.

PMID- 18619696
TI  - Real-time PCR assay for the detection of species of the genus Mannheimia.
AB  - Infections caused by species of the genus Mannheimia cause diverse disease
      complexes in many wild and domestic animals worldwide. Fast and accurate
      detection of single species within the genus remains an unsolved problem till
      today. To resolve this diagnostic challenge, we developed a real-time PCR assay
      for the rapid and specific identification of five species of the genus Mannheimia
      (M. haemolytica, M. varigena, M. ruminalis, M. granulomatis and M. glucosida)
      from bacterial cultures and tissue samples. The assay was validated with
      reference strains, field isolates and bacteria spiked tissue samples. The sodA
      gene was used as target region for species-specific primer pairs. The real-time
      PCR assay demonstrated species specificity for all five examined Mannheimia spp.
      and a rapid test completion time of less than 5 h. This is a considerable
      advantage compared to the traditional phenotyping methods currently used to
      distinguish between the species of the genus. The assay was able to detect
      approximately 10(3) bacterial cells per gram lung tissue sample, as determined
      with spiked tissue samples. We assume that the assay could become useful for fast
      laboratory diagnostic assessment particularly of respiratory infections caused by
      Mannheimia in animals.

PMID- 18619697
TI  - Vitality enhancement of the rehydrated active dry wine yeast.
AB  - In winemaking, spontaneous grape must fermentations have been replaced by
      inoculation of commercial active dry wine yeast (ADWY). Yeast rehydration is the
      key to avoiding stuck and sluggish fermentations. Despite the importance of this
      step, not enough is known about what this process implies for winemaking as a
      whole or about what kind of practices could help to improve it. The main aim of
      this study is to determine the best yeast rehydration conditions for ensuring
      good cell viability and vitality before inoculation into the must. The
      experimental rehydration media in this study can be divided into four groups:
      carbon and nitrogen compounds, metallic ions, oxidant and antioxidant agents, and
      membrane fluidity agents. We studied the biochemical and biophysical behaviour of
      ADWY after rehydration in the various media under oenological conditions, i.e.
      incubation at 37 degrees C for 30 min. The viability of rehydrated yeast cells
      was evaluated by plating, and assessed by fluorescence microscopy and flow
      cytometry. The vitality of rehydrated cells was estimated by indirect impedance.
      The rehydrating solution complemented with magnesium provided the best vitality
      rate because the time taken to reach the activity threshold was cut by two
      thirds. This improvement was also illustrated by the less time needed to stop the
      leakage of intracellular compounds during the rehydration process.

PMID- 18619698
TI  - Prevalence and predictors of obesity among individuals with positive hepatitis C
      antibody in a tertiary referral clinic.
AB  - BACKGROUND/AIMS: To determine the prevalence of obesity and investigate factors
      associated with obesity in a hepatitis C antibody positive clinic population.
      METHODS: We reviewed 3505 patient records (1990-2006) from a liver clinic in
      Toronto. We used regression analysis to explore factors associated with obesity.
      We compared the prevalence of obesity among propensity matched patients by
      hepatitis C ribonucleic acid status. RESULTS: Patients (1118) met inclusion
      criteria. The prevalence of obesity in this clinic population was 28.8%. In
      multiple regression analyses, older age (odds ratio 1.02; 95% confidence interval
      1.00-1.04) and a positive hepatitis C ribonucleic acid test (odds ratio 1.80; 95%
      confidence interval 1.11-2.92) were independently associated with obesity. In the
      analysis comparing 112 propensity matched pairs, the prevalence of obesity was
      significantly higher among hepatitis C ribonucleic acid positive patients than in
      matched patients who tested negative (32.1% vs. 18.8%; p=0.02). Supplemental
      analysis by excluding patients with probable fatty liver disease strengthened the
      association between hepatitis C viremia and obesity. CONCLUSIONS: Hepatitis C
      viremia may be associated with an increased prevalence of obesity observed in a
      tertiary referral clinic for hepatitis C.

PMID- 18619699
TI  - Ultrasonography in patients with Budd-Chiari syndrome: diagnostic signs and
      prognostic implications.
AB  - BACKGROUND/AIMS: We analyzed sonomorphological signs of Budd-Chiari syndrome
      (BCS) and their potential for prognosis prediction. METHODS: Forty-five
      consecutive patients were included. Analysis included the frequencies of
      sonomorphological signs and their predictive value for diagnosis of BCS, mean
      values of laboratory and color Doppler data in different therapeutic groups and
      survival. RESULTS: Specific ultrasound signs were identified at the level of the
      hepatic veins in 71% of the patients and in 33% at the level of the caval vein,
      i.e. thrombosis, stenosis, fibrotic cord or insufficient recanalization of the
      vessels. The frequent non-specific signs were splenomegaly (78%), inhomogeneous
      liver parenchyma (76%), intrahepatic collaterals (73%), caudate lobe hypertrophy
      (67%), ascites (56%) and extrahepatic collaterals (44%). The combination of
      specific signs and "caudate lobe hypertrophy" offered the highest predictive
      value to identify patients with BCS (p=0.014) with a specificity of 100%. Mean
      survival was significantly different between the patients with or without portal
      hypertension (n=25, 41.1+/-7.6, 95% CI (26.2-55.9) versus n=20, 89.4+/-4.5, 95%
      CI (80.5-98.2), p=0.004) and with or without portal vein thrombosis (n=12, 29.8+/
      10.7, 95% CI (8.9-50.7) versus n=33, 79.3+/-6.1, 95% CI (67.4-91.1), p=0.003).
      CONCLUSIONS: We present a comprehensive description of sonomorphological signs in
      BCS. The combination of ultrasound signs "altered hepatic and/or caval veins" and
      "caudate lobe hypertrophy" was the best strategy to diagnose BCS. Patients with
      portal vein thrombosis or portal hypertension have a poor prognosis.

PMID- 18619700
TI  - Expression of multidrug resistance-associated protein 3 and cytotoxic T cell
      responses in patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Multidrug resistance-associated protein 3 (MRP3) is a carrier
      type transport protein belonging to the ABC transporters. It is expressed in
      normal tissues, and enhanced expression in many cancers has been reported. In
      this study, we investigated the usefulness of MRP3 as a target antigen in
      immunotherapy for hepatocellular carcinoma (HCC). METHODS: The MRP3 expression
      level in HCC tissue was measured by quantitative PCR. MRP3-specific T cell
      responses were investigated by several immunological techniques using peripheral
      blood mononuclear cells or tumor-infiltrating lymphocytes. RESULTS: The MRP3
      expression level in HCC tissue was significantly higher than that in non
      cancerous tissue (P<0.05). MRP3-specific cytotoxic T cells (CTLs) could be
      induced regardless of liver function, the presence or absence of HCV infection,
      the blood AFP level, and the stage of HCC. The CTLs showed cytotoxicity against
      HCC cells overexpressing MRP3. A negative correlation was present between the
      MRP3 expression level in HCC tissue and the frequency of MRP3-specific CTLs. The
      frequency of MRP3-specific CTLs increased after HCC treatment, such as
      transcatheter arterial embolization and radiofrequency ablation. CONCLUSIONS: Our
      study demonstrates that MRP3 is a potential candidate for tumor antigen with
      strong immunogenicity in HCC immunotherapy.

PMID- 18619702
TI  - From cost-effectiveness information to decision-making on liquid-based cytology:
      Mind the gap.
AB  - OBJECTIVE: This paper explores the policy process involved in the production of
      cost-effectiveness information in the context of both national and local policy
      making requirements. We use the decision to implement a new technology for
      cervical cancer screening (liquid-based cytology) in England as a case study.
      METHODS: The analysis traces the initial decision by the National Institute of
      Health and Clinical Excellence to commission further research before implementing
      this new technology, the economic data produced as a result, the final decision
      nationally and the implications for decision-makers locally. RESULTS: The paper
      highlights a number of reasons why there may be a gap between the evidence
      produced by a cost-effectiveness analysis and the information needs of the
      decision-maker. For example there are difficulties in estimating whether savings
      in staff time are realisable. In addition, even after a technology has been
      deemed cost-effective and is recommended for national implementation, further
      questions remain at the local level, including identifying the most cost
      effective way to implement a technology, and selecting the best supplier.
      CONCLUSION: In order to make cost-effective implementation decisions, local
      decision-makers require economic data in addition to that required for the
      national recommendation, and this deserves recognition and further research.

PMID- 18619701
TI  - DNA polymorphisms and response to treatment in patients with chronic hepatitis C:
      results from the HALT-C trial.
AB  - BACKGROUND/AIMS: Certain host genetic polymorphisms reportedly affect the
      likelihood of a sustained virological response (SVR) to interferon treatment in
      subjects infected with hepatitis C virus (HCV). As part of the HALT-C trial we
      evaluated genetic associations among patients infected with HCV genotype 1 who
      had failed previous interferon treatment. METHODS: SVR was determined 24 weeks
      after completing treatment with pegylated interferon alfa-2a and ribavirin. Eight
      single nucleotide polymorphisms (SNPs) were selected on the basis of previously
      reported associations with treatment response. Genotypes were assessed by
      polymerase chain reaction-based assays. The percentage of patients who achieved
      SVR was determined for each genotype and for an IL10 promoter diplotype. RESULTS:
      Among 637 non-Hispanic Caucasian patients there were no significant associations
      between genotype for any individual SNP (IL10-1082, IL10-592, TNF-308, TNF-238,
      TGFB1 codon 25, CCL2-2518, EPHX1 codon 113 and AGT-6) and SVR, but SVR was more
      common among the patients who were homozygous for the ACC IL10 promoter diplotype
      (adjusted odds ratio, 3.24; 95% confidence interval, 1.33-7.78; p=0.001).
      CONCLUSIONS: Among non-Hispanic Caucasian patients treated with peginterferon and
      ribavirin after failing previous treatment with interferon, homozygosity for the
      ACC IL10 promoter diplotype was associated with SVR.

PMID- 18619703
TI  - Consumer use of publicly released hospital performance information: assessment of
      the National Hospital Evaluation Program in Korea.
AB  - OBJECTIVE: To assess the extent of consumer use of publicly released hospital
      performance information by the National Health Evaluation Program (HEP) in Korea.
      DESIGN: A questionnaire survey with 385 outpatients visiting four general
      hospitals in Seoul. MAIN OUTCOME MEASURES: The consumer use of performance
      information was assessed by the consumers' intention to: (1) recommend hospitals
      with good performance reports, according to HEP, to their relatives; (2) switch
      to other hospitals with a better performance and (3) keep the performance report
      for future use. RESULTS: Overall, 52-75% of the respondents expressed their
      intention to use the hospital performance information. Logistic regression
      analysis results showed that people would use the performance information if they
      considered HEP to be effective in improving the quality of health care and the
      performance reports to be trustworthy and useful in choosing hospitals.
      CONCLUSION: This study provides evidence that consumers in a health care system
      with few restrictions for provider choice, such as in Korea, have a high
      potential to utilize the provider performance information in their decision
      making. If public use of the performance information becomes common, policy
      makers should acknowledge the critical value of the quality of the performance
      report in order to avoid misleading consumers.

PMID- 18619704
TI  - Public health policy decisions on medical innovations: what role can early
      economic evaluation play?
AB  - OBJECTIVES: Our contribution aims to explore the different ways in which early
      economic data can inform public health policy decisions on new medical
      technologies. METHODS: A literature research was conducted to detect
      methodological contributions covering the health policy perspective. RESULTS:
      Early economic data on new technologies can support public health policy
      decisions in several ways. Embedded in horizon scanning and HTA activities, it
      adds to monitoring and assessment of innovations. It can play a role in the
      control of technology diffusion by informing coverage and reimbursement decisions
      as well as the direct public promotion of healthcare technologies, leading to
      increased efficiency. Major problems include the uncertainty related to economic
      data at early stages as well as the timing of the evaluation of an innovation.
      CONCLUSIONS: Decision-makers can benefit from the information supplied by early
      economic data, but the actual use in practice is difficult to determine. Further
      empirical evidence should be gathered, while the use could be promoted by further
      standardization.

PMID- 18619705
TI  - Ellipticine-induced apoptosis depends on Akt translocation and signaling in lung
      epithelial cancer cells.
AB  - Ellipticine and its analogues were reported as topoisomerase II inhibitors and
      promising antitumor agents. In this work, we showed that the growth of human non
      small-cell-lung-cancer (NSCLC) epithelial cells A549 can be inhibited by
      ellipticine. The inhibitory effect was reverted by PI3K inhibitors. The sub-G(1)
      phase cells after ellipticine treatment appeared at the expense of those that
      accumulated first at S- and G(2)/M phases during the early stage of treatment. We
      showed that the progression leading to cell death was impaired by wortmannin,
      which reverted apoptosis by retaining cells at S- and G(2)/M transition states.
      The characteristic apoptosis marker p53 activation after treatment appeared first
      followed by poly(ADP-ribose)polymerase (PARP) fragmentation. They disappeared
      upon co-treatment with wortmannin and the apoptotic phenotype reversed.
      Furthermore, ellipticine regulated endogenous survival signaling by up-regulating
      phosphorylated Akt that returned to its basal level later. Furthermore,
      ellipticine induced nucleus translocalization of p53 and Akt and recruitment of
      autophagosomes. The autophagic-related cell death was interfered by wortmannin
      and the suppressed growth reverted. The Akt-related cell death also occurred in
      p53-deficient cells with stable expression of exogenous p53. The work showed that
      ellipticine-induced cytotoxicity in NSCLC cells was achieved through autophagy
      and apoptotic death as a result of Akt-modulation. Being a topoisomerase II
      inhibitor, ellipticine proved a regulator in autophagy-related cell death through
      corporation of p53 and Akt.

PMID- 18619706
TI  - Geochemical characterisation of shallow aquifer sediments of Matlab Upazila,
      Southeastern Bangladesh - implications for targeting low-As aquifers.
AB  - High arsenic (As) concentrations in groundwater pose a serious threat to the
      health of millions of people in Bangladesh. Reductive dissolution of Fe(III)
      oxyhydroxides and release of its adsorbed As is considered to be the principal
      mechanism responsible for mobilisation of As. The distribution of As is extremely
      heterogeneous both laterally and vertically. Groundwater abstracted from oxidised
      reddish sediments, in contrast to greyish reducing sediments, contains
      significantly lower amount of dissolved arsenic and can be a source of safe
      water. In order to study the sustainability of that mitigation option, this study
      describes the lithofacies and genesis of the sediments within 60 m depth and
      establishes a relationship between aqueous and solid phase geochemistry. Oxalate
      extractable Fe and Mn contents are higher in the reduced unit than in the
      oxidised unit, where Fe and Mn are present in more crystalline mineral phases.
      Equilibrium modelling of saturation indices suggest that the concentrations of
      dissolved Fe, Mn and PO(4)(3-)-tot in groundwater is influenced by secondary
      mineral phases in addition to redox processes. Simulating As(III) adsorption on
      hydroferric oxides using the Diffuse Layer Model and analytical data gave
      realistic concentrations of dissolved and adsorbed As(III) for the reducing
      aquifer and we speculate that the presence of high PO(4)(3-)-tot in combination
      with reductive dissolution results in the high-As groundwater. The study confirms
      high mobility of As in reducing aquifers with typically dark colour of sediments
      found in previous studies and thus validates the approach for location of wells
      used by local drillers based on sediment colour. A more systematic and
      standardised colour description and similar studies at more locations are
      necessary for wider application of the approach.

PMID- 18619707
TI  - Impact of nonaqueous phase liquid (NAPL) source zone architecture on mass removal
      mechanisms in strongly layered heterogeneous porous media during soil vapor
      extraction.
AB  - An existing multiphase flow simulator was modified in order to determine the
      effects of four mechanisms on NAPL mass removal in a strongly layered
      heterogeneous vadose zone during soil vapor extraction (SVE): a) NAPL flow, b)
      diffusion and dispersion from low permeability zones, c) slow desorption from
      sediment grains, and d) rate-limited dissolution of trapped NAPL. The impacts of
      water and NAPL saturation distribution, NAPL-type (i.e., free, residual, or
      trapped) distribution, and spatial heterogeneity of the permeability field on
      these mechanisms were evaluated. Two different initial source zone architectures
      (one with and one without trapped NAPL) were considered and these architectures
      were used to evaluate seven different SVE scenarios. For all runs, slow diffusion
      from low permeability zones that gas flow bypassed was a dominant factor for
      diminished SVE effectiveness at later times. This effect was more significant at
      high water saturation due to the decrease of gas-phase relative permeability.
      Transverse dispersion contributed to fast NAPL mass removal from the low
      permeability layer in both source zone architectures, but longitudinal dispersion
      did not affect overall mass removal time. Both slow desorption from sediment
      grains and rate-limited mass transfer from trapped NAPL only marginally affected
      removal times. However, mass transfer from trapped NAPL did affect mass removal
      at later time, as well as the NAPL distribution. NAPL flow from low to high
      permeability zones contributed to faster mass removal from the low permeability
      layer, and this effect increased when water infiltration was eliminated. These
      simulations indicate that if trapped NAPL exists in heterogeneous porous media,
      mass transfer can be improved by delivering gas directly to zones with trapped
      NAPL and by lowering the water content, which increases the gas relative
      permeability and changes trapped NAPL to free NAPL.

PMID- 18619708
TI  - Locally-calibrated light transmission visualization methods to quantify
      nonaqueous phase liquid mass in porous media.
AB  - Five locally-calibrated light transmission visualization (LTV) methods were
      tested to quantify nonaqueous phase liquid (NAPL) mass and mass reduction in
      porous media. Tetrachloroethylene (PCE) was released into a two-dimensional
      laboratory flow chamber packed with water-saturated sand which was then flushed
      with a surfactant solution (2% Tween 80) until all of the PCE had been dissolved.
      In all the LTV methods employed here, the water phase was dyed, rather than the
      more common approach of dyeing the NAPL phase, such that the light adsorption
      characteristics of NAPL did not change as dissolution progressed. Also, none of
      the methods used here required the use of external calibration chambers. The five
      visualization approaches evaluated included three methods developed from
      previously published models, a binary method, and a novel multiple wavelength
      method that has the advantage of not requiring any assumptions about the intra
      pore interface structure between the various phases (sand/water/NAPL). The new
      multiple wavelength method is also expected to be applicable to any translucent
      porous media containing two immiscible fluids (e.g., water-air, water-NAPL).
      Results from the sand-water-PCE system evaluated here showed that the model that
      assumes wetting media of uniform pore size (Model C of Niemet and Selker, 2001)
      and the multiple wavelength model with no interface structure assumptions were
      able to accurately quantify PCE mass reduction during surfactant flushing. The
      average mass recoveries from these two imaging methods were greater than 95% for
      domain-average NAPL saturations of approximately 2.6x10(-2), and were
      approximately 90% during seven cycles of surfactant flushing that sequentially
      reduced the average NAPL saturation to 7.5x10(-4).

PMID- 18619709
TI  - Adherence to acitretin and home narrowband ultraviolet B phototherapy in patients
      with psoriasis.
AB  - BACKGROUND: In the treatment of psoriasis, patient adherence to oral medications
      is poor and even worse for topical therapy. However, few data exist about
      adherence rates to home phototherapy, adding to concerns about the
      appropriateness of home phototherapy as a psoriasis treatment option. OBJECTIVE:
      We sought to assess adherence to both oral acitretin and home ultraviolet B
      phototherapy for the treatment of psoriasis. METHODS: In all, 27 patients with
      moderate to severe psoriasis were treated with 10 to 25 mg of acitretin daily,
      combined with narrowband ultraviolet B, 3 times weekly at home, for 12 weeks.
      Adherence to acitretin was monitored by an electronic monitoring medication
      bottle cap, and to phototherapy by a light-sensing data logger. RESULTS:
      Adherence data were collected on 22 patients for acitretin and 16 patients for
      adherence to ultraviolet B. Mean adherence to acitretin decreased steadily during
      the 12-week trial (slope -0.24), whereas mean adherence to home phototherapy
      remained steady at 2 to 3 d/wk. Adherence was similar between patients who
      reported side effects and those who did not. LIMITATIONS: Small sample size and
      lack of follow-up on some patients were limitations of this study. CONCLUSIONS:
      Adherence rates to home phototherapy were very good and higher than adherence
      rates for the oral medication. Side effects of treatment were well tolerated in
      this small group and did not affect use of the treatment. Home phototherapy with
      acitretin may be an appropriate option for some patients with extensive
      psoriasis.

PMID- 18619710
TI  - Patient comprehension of emergency department care and instructions: are patients
      aware of when they do not understand?
AB  - STUDY OBJECTIVE: To be able to adhere to discharge instructions after a visit to
      the emergency department (ED), patients should understand both the care that they
      received and their discharge instructions. The objective of this study is to
      assess, at discharge, patients' comprehension of their ED care and instructions
      and their awareness of deficiencies in their comprehension. METHODS: We conducted
      structured interviews of 140 adult English-speaking patients or their primary
      caregivers after ED discharge in 2 health systems. Participants rated their
      subjective understanding of 4 domains: (1) diagnosis and cause; (2) ED care; (3)
      post-ED care, and (4) return instructions. We assessed patient comprehension as
      the degree of agreement (concordance) between patients' recall of each of these
      domains and information obtained from chart review. Two authors scored each case
      independently and discussed discrepancies before providing a final concordance
      rating (no concordance, minimal concordance, partial concordance, near
      concordance, complete concordance). RESULTS: Seventy-eight percent of patients
      demonstrated deficient comprehension (less than complete concordance) in at least
      1 domain; 51% of patients, in 2 or more domains. Greater than a third of these
      deficiencies (34%) involved patients' understanding of post-ED care, whereas only
      15% were for diagnosis and cause. The majority of patients with comprehension
      deficits failed to perceive them. Patients perceived difficulty with
      comprehension only 20% of the time when they demonstrated deficient
      comprehension. CONCLUSION: Many patients do not understand their ED care or their
      discharge instructions. Moreover, most patients appear to be unaware of their
      lack of understanding and report inappropriate confidence in their comprehension
      and recall.

PMID- 18619712
TI  - Odor identification impairment in carriers of ApoE-varepsilon4 is independent of
      clinical dementia.
AB  - The ApoE gene is expressed in olfactory brain structures and is believed to play
      a role in neuronal regenerative processes as well as in development of
      Alzheimer's disease (AD), the most common form of dementia. The varepsilon4
      allele has been reported to be associated with compromised odor identification
      ability in the elderly, and this deficit has been interpreted as a sign of pre
      diagnostic AD. However, because it has not been demonstrated that the
      relationship between the varepsilon4 allele and odor identification is mediated
      by dementia, it is possible that the varepsilon4 allele may have an effect on
      odor identification over and above any effects of dementia. The present study
      investigated effects of ApoE-status on odor identification in a large, population
      based sample (n=1236) of adults (45-80 years), who were assessed for dementia at
      time of testing and 5 years later. The results showed that the varepsilon4 allele
      was associated with an odor identification deficit among elderly participants (75
      80). Critically, this effect remained after current and pre-diagnostic dementia,
      vocabulary, global cognitive status and health variables were partialled out. The
      present results suggest that the ApoE gene plays a role in olfactory functioning
      that is independent of dementia conversion within 5 years.

PMID- 18619711
TI  - Molecular polymorphism of Abeta in Alzheimer's disease.
AB  - Alzheimer's disease is defined pathologically by the presence of senile plaques,
      which consist primarily of extracellular aggregates of fibrillar Abeta peptide,
      and neurofibrillary tangles, which are abnormal, intracellular bundles of
      fibrillar tau protein. The advent of amyloid binding agents as diagnostic imaging
      probes for Alzheimer's disease (AD) has made it imperative to understand at a
      molecular and disease level what these ligands are reporting. In addition to
      improving the accuracy of diagnosis, we argue that these selective ligands can
      serve as probes for molecular polymorphisms that may govern the pathogenicity of
      abnormal protein aggregates.

PMID- 18619713
TI  - Design, synthesis and evaluation of novel uracil acetamide derivatives as
      potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase.
AB  - The ubiquitous enzyme dUTP nucleotidohydrolase (dUTPase) catalyses the hydrolysis
      of dUTP to dUMP and can be considered as the first line of defence against
      incorporation of uracil into DNA. Inhibition of this enzyme results in over
      incorporation of uracil into DNA, leading to DNA fragmentation and cell death and
      is therefore lethal. By taking advantage of structural differences between the
      human and Plasmodium dUTPase, selective inhibitors of the enzyme can be designed
      and synthesised with the aim of being developed into novel anti-parasitic drugs.
      Analogue based design was used to target the Plasmodium falciparum dUTPase
      (PfdUTPase). The structures of previously discovered selective inhibitors of the
      PfdUTPase were modified by insertion of an amide bond. A series of tritylated
      uracil acetamide derivatives were synthesised and assessed for inhibition of the
      enzyme and parasite growth in vitro. These compounds were weak inhibitors of the
      PfdUTPase.

PMID- 18619714
TI  - A novel QSAR model for predicting the inhibition of CXCR3 receptor by 4-N-aryl
      [1,4] diazepane ureas.
AB  - A linear quantitative structure-activity relationship (QSAR) model is presented
      for modeling and predicting the inhibition of CXCR3 receptor. The model was
      produced by using the multiple linear regression (MLR) technique on a database
      that consists of 32 recently discovered 4-N-aryl-[1,4] diazepane ureas. The key
      conclusion of this study is that 3k, ChiInf8, ChiInf0, AtomCompTotal and ClogP
      affect significantly the inhibition of CXCR3 receptor by diazepane ureas. The
      selected physicochemical descriptors serve as a first guideline for the design of
      novel and potent antagonists of CXCR3.

PMID- 18619715
TI  - [Intra-alveolar pulmonary haemorrhage, an unusual manifestation of the primary
      antiphospholipid syndrome].
AB  - Pulmonary embolism is the main pulmonary manifestation of primary
      antiphospholipid syndrome. Other pulmonary manifestations including intra
      alveolar haemorrhage are less common. We report a 36-year-old man with a primary
      antiphospholipid syndrome who presented with an acute respiratory failure due to
      the association of pulmonary embolism and intra-alveolar haemorrhage. This
      diagnosis should be systematically considered as it is life threatening and
      requires a specific therapy.

PMID- 18619716
TI  - [Systemic lupus erythematosus: future therapeutic avenues].
AB  - During the last decade, new biotherapies have been developed for the treatment of
      systemic autoimmune diseases, especially for systemic lupus erythematosus (SLE).
      These new approaches are based on a better understanding of the auto-immune
      response. Targets of these new treatments are all the steps of the immune
      response. These new therapies are: (1) "B lymphocyte (BL)" inhibitors such as
      anti-CD20 monoclonal antibody, anti-CD22 monoclonal antibody, BlyS antagonists,
      tolerogens of pathogenic-antibody secreting LB (LJP 394) and edratide; (2)
      "Inhibitors of the costimulation" between antigen-presenting cells and T
      lymphocyte (TL) like monoclonal anti-CD40 ligand antibody or CTLA-4-Ig
      (abatacept); (3) "Cytokine antagonists" inhibiting key cytokines of SLE:
      interleukin-10, interferon-alpha, interleukin-6 and TNF. These new therapies are
      currently under development in SLE.

PMID- 18619717
TI  - [Influence of hospitalisation on the elderly people polypharmacy].
AB  - INTRODUCTION: The objective of this study was to analyse the influence of
      hospitalisation on the polypharmacy of elderly people in internal medicine.
      METHODS: Prescriptions before hospitalisation and after discharge were
      prospectively collected and analysed. The percentages of pharmaceutical
      medication classes used before and after hospitalisation were compared using
      marginal homogeneity's test for paired series. RESULTS: One hundred and sixteen
      patients (mean age: 79 years) were included in this study. The number of drugs
      prescribed amounted to 6.4 before hospitalisation and 6.7 at discharge.
      Hospitalisation did not lead to reduction in the amount of prescribed drugs but
      some medications were modified. We observed a significant reduction in beta
      blockers (25 to 19.8%, P=0.035) and lipid-lowering drugs (21.6 to 15.5%,
      P=0.058). On the other hand, the laxative medication was increased at discharge
      (19.8 to 34.5%, P=0.001). Similarly, there was an increase in psycholeptic drugs
      after hospitalisation (34.5 to 44%, P=0.007). CONCLUSION: These results pointed
      out firstly the polypharmacy observed in elderly patients and secondly the
      difficulty to reassess prescriptions. Our results should heighten clinicians'
      awareness of polypharmacy of elderly patients and of the usefulness of performing
      an individual assessment of the various drugs prescribed to a patient. The
      hierarchical organisation of disorders and drugs should allow to optimise the
      safety of the medications and decrease iatrogenic events.

PMID- 18619719
TI  - An intramuscular haemangioma of the tongue.

PMID- 18619718
TI  - The Bologna process: the quiet revolution in nursing higher education.
AB  - This paper will trace the history and continuing development of the 'Bologna
      Process' whose aim is to create convergence of higher education across the
      European Union by 2010. It will identify how this will have profound implications
      for graduate nurse education and present opportunities for students, graduate
      nurses, teachers and researchers in terms of mobility and employment as well as
      collaborative research. Although supportive, the paper questions whether these
      reforms will provide the much-needed impetus to raise the educational status of
      the vast majority of European nurses from diploma to graduate level. Barriers to
      achieving the ideal of an all-graduate EU nursing workforce are discussed in an
      economic and political context. The main thrust of the paper is that, if this
      were achieved, it would have a positive impact on the health care systems and
      populations of participating countries as well as their economies.

PMID- 18619720
TI  - Creating intoxigenic environments: marketing alcohol to young people in Aotearoa
      New Zealand.
AB  - Alcohol consumption among young people in New Zealand is on the rise. Given the
      broad array of acute and chronic harms that arise from this trend, it is a major
      cause for alarm and it is imperative that we improve our knowledge of key drivers
      of youth drinking. Changes wrought by the neoliberal political climate of
      deregulation that characterised the last two decades in many countries including
      Aotearoa (Aotearoa is a Maori name for New Zealand) New Zealand have transformed
      the availability of alcohol to young people. Commercial development of youth
      alcohol markets has seen the emergence of new environments, cultures and
      practices around drinking and intoxication but the ways in which these changes
      are interpreted and taken up are not well understood. This paper reports findings
      from a qualitative research project investigating the meaning-making practices of
      young people in New Zealand in response to alcohol marketing. Research data
      included group interviews with a range of Maori and Pakeha young people at three
      time periods. Thematic analyses of the youth data on usages of marketing
      materials indicate naturalisation of tropes of alcohol intoxication. We show how
      marketing is used and enjoyed in youth discourses creating and maintaining what
      we refer to as intoxigenic social environments. The implications are considered
      in light of the growing exposure of young people to alcohol marketing in a
      discussion of strategies to manage and mitigate its impacts on behaviour and
      consumption.

PMID- 18619721
TI  - Mental number line disruption in a right-neglect patient after a left-hemisphere
      stroke.
AB  - A right-neglect patient with focal left-hemisphere damage to the posterior
      superior parietal lobe was assessed for numerical knowledge and tested on the
      bisection of numerical intervals and visual lines. The semantic and verbal
      knowledge of numbers was preserved, whereas the performance in numerical tasks
      that strongly emphasize the visuo-spatial layout of numbers (e.g. number
      bisection) was impaired. The behavioral pattern of error in the two bisection
      tasks mirrored the one previously described in left-neglect patients. In other
      words, our patient misplaced the subjective midpoint (numerical or visual) to the
      left as function of the interval size. These data, paired with the patient's
      lesion site are strictly consistent with the tripartite organization of number
      related processes in the parietal lobes as proposed by Dehaene and colleagues.
      According to these authors, the posterior superior parietal lobe on both
      hemispheres underpins the attentional orientation on the putative mental number
      line, the horizontal segment of the intraparietal sulcus is bilaterally related
      to the semantic of the numerical domain, whereas the left angular gyrus subserves
      the verbal knowledge of numbers. In summary, our results suggest that the
      processes involved in the navigation along the mental number line, which are
      related to the parietal mechanisms for spatial attention, and the processes
      involved in the semantic and verbal knowledge of numbers, are dissociable.

PMID- 18619722
TI  - A toxicogenomics approach for early assessment of potential non-genotoxic
      hepatocarcinogenicity of chemicals in rats.
AB  - For assessing carcinogenicity in animals, it is difficult and costly, an
      alternative strategy has been desired. We explored the possibility of applying a
      toxicogenomics approach by using comprehensive gene expression data in rat liver
      treated with various compounds. As prototypic non-genotoxic hepatocarcinogens,
      thioacetamide (TAA) and methapyrilene (MP) were selected and 349 commonly changed
      genes were extracted by statistical analysis. Taking both compounds as positive
      with six compounds, acetaminophen, aspirin, phenylbutazone, rifampicin, alpha
      naphthylisothiocyanate, and amiodarone as negative, prediction analysis of
      microarray (PAM) was performed. By training and 10-fold cross validation, a
      classifier containing 112 probe sets that gave an overall success rate of 95% was
      obtained. The validity of the present discriminator was checked for 30 chemicals.
      The PAM score showed characteristic time-dependent increases by treatment with
      several non-genotoxic hepatocarcinogens, including TAA, MP, coumarin, ethionine
      and WY-14643, while almost all of the non-carcinogenic samples were correctly
      predicted. Measurement of hepatic glutathione content suggested that MP and TAA
      cause glutathione depletion followed by a protective increase, but the protective
      response is exhausted during repeated administration. Therefore, the presently
      obtained PAM classifier could predict potential non-genotoxic
      hepatocarcinogenesis within 24 h after single dose and the inevitable pseudo
      positives could be eliminated by checking data of repeated administrations up to
      28 days. Tests for carcinogenicity using rats takes at least 2 years, while the
      present work suggests the possibility of lowering the time to 28 days with high
      precision, at least for a category of non-genotoxic hepatocarcinogens causing
      oxidative stress.

PMID- 18619723
TI  - Dasatinib inhibits the growth and survival of neoplastic human eosinophils (EOL
      1) through targeting of FIP1L1-PDGFRalpha.
AB  - OBJECTIVE: Chronic eosinophilic leukemia (CEL) is a myeloproliferative disorder
      characterized by molecular and/or cytogenetic evidence of clonality of
      eosinophils, marked eosinophilia, and organ damage. In many patients, the
      transforming mutation FIP1L1-PDGFRalpha and the related CHIC2 deletion are found.
      The respective oncoprotein, FIP1L1-PDGFRalpha, is considered to play a major role
      in malignant cell growth in CEL. The tyrosine kinase (TK) inhibitor imatinib
      (STI571) has been described to counteract the TK activity of FIP1L1-PDGFRalpha in
      most patients. However, not all patients with CEL show a response to imatinib.
      Therefore, several attempts have been made to identify other TK inhibitors that
      counteract growth of neoplastic eosinophils. MATERIALS AND METHODS: We provide
      evidence that dasatinib, a multi-targeted kinase inhibitor, blocks the growth and
      survival of EOL-1, an eosinophil leukemia cell line carrying FIP1L1-PDGFRalpha.
      RESULTS: The effects of dasatinib on proliferation of EOL-1 cells were dose
      dependent, with an IC50 of 0.5 to 1 nM, which was found to be in the same range
      when compared to IC50 values produced with imatinib. Dasatinib was also found to
      induce apoptosis in EOL-1 cells in a dose-dependent manner (IC50: 1-10 nM). The
      apoptosis-inducing effects of dasatinib on EOL-1 cells were demonstrable by light
      microscopy, flow cytometry, and in a TUNEL assay. In Western blot experiments,
      dasatinib completely blocked the phosphorylation of FIP1L1-PDGFRalpha in EOL-1
      cells. CONCLUSIONS: Dasatinib inhibits the growth of leukemic eosinophils through
      targeting of the disease-related oncoprotein FIP1L1-PDGFRalpha. Based on this
      observation, dasatinib may be considered as a new interesting treatment option
      for patients with CEL.

PMID- 18619724
TI  - AKR-501 (YM477) in combination with thrombopoietin enhances human
      megakaryocytopoiesis.
AB  - OBJECTIVE: AKR-501 (YM477) is an orally active thrombopoietin (TPO) receptor
      agonist that mimics the biological effect of TPO in vitro and in vivo. Here, we
      report that AKR-501 in combination with TPO has additive effect on
      megakaryocytopoiesis. MATERIALS AND METHODS: Granulocyte colony-stimulating
      factor-mobilized human peripheral blood CD34+ cells were cultured with AKR-501,
      TPO, or a combination of the two in serum-free liquid culture system. The numbers
      of hematopoietic progenitor cells, megakaryocytic progenitor cells, and
      megakaryocytes were measured using flow cytometry. Further, the effect of AKR-501
      on TPO binding to TPO receptor was examined. RESULTS: Both AKR-501 and TPO alone
      increased the number of megakaryocytes, and the maximum activities of AKR-501 and
      TPO were similar. Interestingly, in the presence of TPO concentrations producing
      maximal stimulation, the addition of AKR-501 increased the number of
      megakaryocytes to about 200% of that generated with TPO only. In the time course
      experiment, the combination of AKR-501 and TPO augmented the numbers of
      hematopoietic progenitor cells and colony-forming unit in culture in the early
      stages. Thus, the combination of AKR-501 and TPO enhanced not only the
      differentiation into megakaryocytes, but also the expansion of human
      hematopoietic progenitor cells. Further, AKR-501 did not inhibit TPO binding to
      the TPO receptor. This result indicated the possibility that AKR-501 and TPO may
      act simultaneously on the TPO receptor, and this could be responsible for their
      additive effect of on megakaryocytopoiesis. CONCLUSIONS: This study suggests that
      AKR-501 would be useful for the treatment of thrombocytopenia even at high plasma
      levels of endogenous TPO following chemotherapy.

PMID- 18619725
TI  - Reversible commitment to differentiation by human multipotent stromal cells in
      single-cell-derived colonies.
AB  - OBJECTIVE: Human multipotent stromal cells readily form single-cell-derived
      colonies when plated at clonal densities. However, the colonies are heterogeneous
      because cells from a colony form new colonies that vary in size and
      differentiation potential when replated at clonal densities. The experiments here
      tested the hypothesis that cells in the inner regions of colonies are partially
      differentiated, but the differentiation is reversible. MATERIALS AND METHODS:
      Cells were separately isolated from the dense inner (IN) regions and less-dense
      outer regions (OUT) of single-cell-derived colonies. Cells were then compared by
      assays of their transcriptomes and proteins, and for clonogenicity and
      differentiation. RESULTS: IN cells expressed fewer cell-cycle genes and higher
      levels of genes for extracellular matrix than the OUT cells. When transferred to
      differentiation medium, differentiation of the colonies occurred primarily in the
      IN regions. However, the IN cells were indistinguishable from OUT cells when
      replated at clonal densities and assayed for rates of propagation and
      clonogenicity. Also, colonies formed by IN cells were similar to colonies formed
      by OUT cells because they had distinct IN and OUT regions. Cultures of IN and OUT
      cells remained indistinguishable through multiple passages (30 to 75 population
      doublings), and both cells formed colonies that were looser and less dense as
      they were expanded. CONCLUSIONS: The results demonstrated that cells in the IN
      region of single-cell-derived colonies are partially differentiated, but the
      differentiation can be reversed by replating the cells at clonal densities.

PMID- 18619727
TI  - Mesenchymal stromal cells lose their immunosuppressive potential after
      allotransplantation.
AB  - OBJECTIVE: The stem cell fraction of mesenchymal stromal cells (MSCs) is capable
      of self-renewal and under inductive conditions differentiates into bone,
      cartilage, hematopoietic stroma, and other mesenchymal tissues. Therefore, MSCs
      represent a promising source for hard tissue repair therapies. MSCs are also
      immunosuppressive and prevent activation of allogeneic lymphocytes in vitro. Thus
      it has been suggested that they might be able to engraft in allogeneic recipients
      and downregulate recipients' immunity. In this study we examined whether MSCs
      retain their immunomodulating properties in vivo after allotransplantation.
      MATERIALS AND METHODS: MSCs were propagated from bone marrow (BM), placenta, or
      umbilical cord tissues. Using a murine parental-into-F1 model of graft-vs-host
      disease (GVHD) we tried to control GVHD by intravenous transplanting parental or
      recipient MSCs together with parental lymphocytes (day 0) and on days +7 and +14.
      MSCs' immunosuppressive potential in vivo was also examined by comparing their
      ability to construct ectopic bone after local transplantation with osteogenic
      inductor (demineralized bone matrix) under the kidney capsule of syngeneic and
      allogeneic recipients. RESULTS: Repeated IV MSC injections failed to reduce GVHD
      related recipient mortality. Local implantation of MSCs propagated from BM,
      placenta or umbilical cord resulted in ectopic bone formation in syngeneic
      recipients and in transplant rejection by allogeneic mice. CONCLUSION: MSCs lose
      their immunosuppressive potential in mismatched setting.

PMID- 18619726
TI  - Dasatinib exerts an immunosuppressive effect on CD8+ T cells specific for viral
      and leukemia antigens.
AB  - OBJECTIVE: To investigate the inhibitory effects of dasatinib on proliferation,
      function, and signaling events on CD8+T cells. MATERIALS AND METHODS:
      Carboxyfluorescein diacetate succinimidyl ester and 5-bromo-2-deoxyuridine were
      used to detect proliferation and cell cycle of CD8+T cells treated with
      dasatinib, respectively. Frequency and function of viral and leukemia-antigen
      specific CD8+T cells from healthy donors were measured by tetramer staining and
      ELISPOT assay. Western blotting analysis was performed to detect T-cell receptor
      (TCR), nuclear factor kappa B (NF-kappaB) and Src signaling events in T cells
      treated with dasatinib or imatinib. RESULTS: Dasatinib inhibited proliferation of
      CD8+T cells in a dose-dependent manner, which was associated with lower secretion
      of interferon-gamma and granzyme B, as well as with arrest of CD8+T cells in the
      G0/G1 phase of cell cycle. Inhibition of CD8+T cells was proven for blood samples
      from a patient under dasatinib medication when compared with their T-cell status
      without dasatinib. Western blotting confirmed that these effects were mediated
      through downregulation of the phosphorylation level of molecules from the TCR and
      the NF-kappaB signaling transduction cascade. Dasatinib proved to be more potent
      than imatinib on Src and TCR signaling events in Jurkat T cells. CONCLUSION: Our
      study demonstrated that dasatinib impaired proliferation and function of CD8+T
      cells via TCR and NF-kappaB signaling events without inducing apoptosis.
      Therefore, dasatinib might alter the graft-vs-leukemia effect and the graft-vs
      host disease after allogeneic stem cell transplantation sustained by CD8+T cells.
      Dasatinib might also be used as a novel immunosuppressant agent.

PMID- 18619728
TI  - Environmental bonds and the challenge of long-term carbon sequestration.
AB  - The potential to capture carbon from industrial sources and dispose of it for the
      long-term, known as carbon capture and sequestration (CCS), is widely recognized
      as an important option to reduce atmospheric carbon dioxide emissions.
      Specifically, CCS has the potential to provide emissions cuts sufficient to
      stabilize greenhouse gas levels, while still allowing for the continued use of
      fossil fuels. In addition, CCS is both technologically-feasible and commercially
      viable compared with alternatives with the same emissions profile. Although the
      concept appears to be solid from a technical perspective, initial public
      perceptions of the technology are uncertain. Moreover, little attention has been
      paid to developing an understanding of the social and political institutional
      infrastructure necessary to implement CCS projects. In this paper we explore a
      particularly dicey issue--how to ensure adequate long-term monitoring and
      maintenance of the carbon sequestration sites. Bonding mechanisms have been
      suggested as a potential mechanism to reduce these problems (where bonding refers
      to financial instruments used to ensure regulatory or contractual commitments).
      Such mechanisms have been successfully applied in a number of settings (e.g., to
      ensure court appearances, completion of construction projects, and payment of
      taxes). The paper examines the use of bonding to address environmental problems
      and looks at its possible application to nascent CCS projects. We also present
      evidence on the use of bonding for other projects involving deep underground
      injection of materials for the purpose of long-term storage or disposal.

PMID- 18619729
TI  - Emerging conflict in collaborative mapping: towards a deeper understanding?
AB  - In spatial planning and environmental management, maps are found very helpful in
      many situations, but in other situations they may also deepen conflicts or be
      ignored. This paper addresses the question what explains such phenomena, with
      particular emphasis on, and reference to, collaborative policymaking settings in
      the Netherlands. We have elaborated the concept of 'frames' and 'framing' to
      structure and analyze the function of maps in the context of deliberative
      policymaking. With help of discourse analysis, a method adopted from the policy
      sciences, we have observed ongoing multi-actor processes and focused on
      discussions around maps in several case studies. From the observations of both
      the maps themselves and the discussions and actions with the maps, we have
      interpreted the meaning and frames represented 'in' the map images, as well as
      the various perspectives of actors 'on' the collaborative use of the map. We have
      conceptualized three fundamentally different perspectives or frames on the
      function of maps in the decision-making process. The cross-frame debate over maps
      is illustrated with the recollection of one particular map-making example. We
      conclude that the conflicts observed in a number of case studies can be
      adequately explained with help of the three identified frames, and provide some
      recommendations for the profession of mapping.

PMID- 18619730
TI  - Ten recently identified associations between nsSNPs and colorectal cancer could
      not be replicated in German families.
AB  - Ten non-synonymous single nucleotide polymorphisms (nsSNPs), which were recently
      associated with colorectal cancer risk in a comprehensive, array based study
      (AKAP9 M463I, DKK3 G335R, AMPD1 Q12X, LIPC L356F, PSMB9 V32I, THBS1 N700S, CA6
      S90G, ASCC3 C1995S, DHX36 S416C and CPA4 G303C) were re-evaluated in the present
      study based on 626 German familial non-HNPCC colorectal cancer patients and 736
      healthy controls. No associations of any of the 10 nsSNPs with colorectal cancer
      could be replicated. The combined analyses indicated that further research based
      on additional independent samples is required.

PMID- 18619731
TI  - Prediction of autoignition temperatures of organic compounds by the structural
      group contribution approach.
AB  - A model to predict the autoignition temperatures (AIT) of organic compounds is
      proposed based on the structural group contribution (SGC) approach. This model
      has been built up using a 400-compound training set; the fitting ability for
      these training data is 0.8474, with an average error of 32K and an average error
      percentage of 4.9%. The predictive capability of the proposed model has been
      demonstrated on an 83-compound validation set; the predictive capability for
      these validation data is about 0.5361, with an average error of 70K and an
      average error percentage of 11.0%. The proposed model is shown to be more
      accurate than those of other published works. This improvement is largely
      attributed to the modifications of the group definitions for estimating the AIT
      instead of the type of empirical model chosen. Through the Q(2) value and
      hypothesis testing, it was found that the empirical model should be chosen as a
      polynomial of degree 3. As compared to the known errors in experimentally
      determining the AIT, the proposed method offers a reasonable estimate of the AIT
      for the organic compounds in the training set, and can also approximate the AIT
      for compounds whose AIT is as yet unknown or not readily available to within a
      reasonable accuracy.

PMID- 18619732
TI  - Radioactive contamination in Croatia by phosphate fertilizer production.
AB  - The contents of natural radionuclides (radium, uranium and potassium) were
      measured in the area of a phosphate fertilizer factory in central Croatia, as a
      part of extended and still ongoing monitoring program of radioactive
      contamination of human environment in Croatia that is performed by the Radiation
      Protection Unit of the Institute for Medical Research and Occupational Health in
      Zagreb. Activity concentrations in all analysed media (waste water, trickling
      water from piezometers, phosphogypsum deposit and final products) considerably
      fluctuated, especially in phosphogypsum and waste water. Mean (226)Ra activity
      concentration in waste phosphogypsum was measured to be 483+/-190 Bqkg(-1). Based
      on that value, it was estimated that 4 million m(3) of phosphogypsum that have
      been deposited up to now contain about 4.3 x 10(12) Bq, i.e. about 200 g of
      (226)Ra. However, effective dose for an adult that would be incurred by
      consumption of water from nearby wells was estimated to be 5.3+/-1.3 microSv. The
      results show that (226)Ra activities cause effective doses, which are below the
      recommended maximum as the estimated annual (226)Ra effective dose does not
      exceed 0.1 mSv as recommended by the World Health Organization.

PMID- 18619733
TI  - Development of environmental consequence index (ECI) using fuzzy composite
      programming.
AB  - Estimation of environmental consequences of hazardous substances in chemical
      industries is a very difficult task owing to (i) diversity in the types of
      hazards and their effects, (ii) location, and (ii) uncertainty in input
      information. Several indices have been developed over the years to estimate the
      environmental consequences. In this paper, a critical literature review was done
      on the existing environmental indices to identify their applications and
      limitations. The existing indices lack in consideration of all environmental
      consequence factors such as material hazard factors, dispersion factors,
      environmental effects, and their uncertainty. A new methodology is proposed for
      the development of environmental consequence index (ECI), which can overcome the
      stated limitations. Moreover, the recently developed fuzzy composite programming
      (FCP) is used to take care of the uncertainty in estimation. ECI is applied to
      benzene extraction unit (BEU) of a petrochemical industry situated in eastern
      part of India. The ECI for all the eight sections of BEU are estimated and
      ranked. The results are compared with well-established indices such as Dow fire
      and explosion index, safety weight hazard index (SWeHI), and environmental
      accident index (EAI). The proposed ECI may outperform other indices based on its
      detailed consideration of the factors and performed equally to Dow F&E index, and
      EAI in most of the cases for the present application.

PMID- 18619734
TI  - Role of metal ion incorporation in ion exchange resin on the selectivity of
      fluoride.
AB  - Indion FR 10 resin has sulphonic acid functional group (H(+) form) possesses
      appreciable defluoridation capacity (DC) and its DC has been enhanced by chemical
      modification into Na(+) and Al(3+) forms by loading respective metal ions in H(+)
      form of resin. The DCs of Na(+) and Al(3+) forms were found to be 445 and 478 mg
      F(-)/kg, respectively, whereas the DC of H(+) form is 265 mg F(-)/kg at 10 mg/L
      initial fluoride concentration. The nature and morphology of sorbents are
      characterized using FTIR and SEM analysis. The fluoride sorption was explained
      using the Freundlich, Langmuir and Redlich-Peterson isotherms and kinetic models.
      The calculated thermodynamic parameters such as DeltaG degrees, DeltaH degrees,
      DeltaS degrees and sticking probability (S(*)) explains the nature of sorption.
      Comparison was also made by the elution capacity of these resins in order to
      select a cost effective material. A field trial was carried out to test the
      suitability of the resins with fluoride water collected from a nearby fluoride
      endemic area.

PMID- 18619735
TI  - Flea blood feeding patterns in cats treated with oral nitenpyram and the topical
      insecticides imidacloprid, fipronil and selamectin.
AB  - A series of studies was conducted to determine the effect of systemically and
      topically active insecticides on blood consumption by fleas (Ctenocephalides
      felis). Infestations were conducted by placing fleas into plexi-glass chambers
      attached to the lateral rib cage of domestic short-hair cats. After pre-defined
      periods, fleas and flea feces were extracted using vacuum aspiration and
      spectrophotometrically analyzed for hemoglobin using Drabkin's reagent. To
      determine how rapidly nitenpyram kills actively feeding fleas, a single oral
      treatment was administered 24h after infestation. To determine the effect of
      nitenpyram on blood consumption of newly acquired fleas, cats were infested with
      fleas 1h post-treatment and fleas and flea feces from both studies were extracted
      at 15, 30, 60, 120, 240 and 480min post-treatment or post-infestation. To compare
      the effects of topically versus systemically active insecticides, 20 cats each
      with 2 chambers attached, were randomly allocated among groups and were infested
      with fleas 1h after each of 4 nitenpyram treatments, or at 7, 14, 21 and 28 days
      after a single application of commercial spot-on formulations of fipronil,
      imidacloprid or selamectin. Infestations were also completed for untreated
      (control) cats. Twenty-four hours after infestation, fleas and flea feces were
      removed for host blood quantification. If at any time, flea blood consumption in
      a treated group did not significantly differ from that of fleas infesting
      controls, that treatment group was withdrawn from the study. Nitenpyram effects
      on actively feeding fleas were first observed at 60min post-dosing when 38% of
      fleas were dead or moribund, and at 240min 100% were dead or moribund. Nitenpyram
      produced a significant reduction in flea blood consumption (p<0.05), which
      appeared to cease 15min after infestation. For the treatment comparisons,
      significantly more (p<0.05) blood was consumed by fleas taken from imidacloprid
      and fipronil-treated cats than from the nitenpyram or selamectin groups. Only on
      nitenpyram- or selamectin-treated cats were there significant reductions (p<0.05)
      in flea blood consumption on days 21 and 28, with significant difference (p>0.05)
      between these two groups on day 28. In this study systemically acting
      insecticides such as nitenpyram, and the topically applied but systemically
      active insecticide selamectin, were more effective in interfering with flea blood
      feeding than were imidacloprid and fipronil.

PMID- 18619736
TI  - Haplotypic variability within the mitochondrial gene encoding for the cytochrome
      c oxidase 1 (cox1) of Cylicocyclus nassatus (Nematoda, Strongylida): evidence for
      an affiliation between parasitic populations and domestic and wild equid hosts.
AB  - This study investigated the genetic variability within Cylicocyclus nassatus
      (Nematoda, Strongylida, Cyathostominae) collected from different domestic and
      wild hosts (i.e. horse, donkey, Przewalskii horse, tarpan and Turkmen kulan) and
      localities in Europe and/or USA. The ribosomal Internal Transcribed Spacer 2
      (ITS2) and the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were PCR
      amplified and sequences characterized from seventy individual parasitic
      specimens. While ITS2 displayed 0-0.6% variation rate among all individual adult
      specimens of C. nassatus examined, 22 different sequence variants (haplotypes) of
      cox1 were detected. Nucleotide variation was detected at 75 of the total 689
      positions (overall 10.8% rate of intraspecific nucletidic difference) in the
      cox1, with the absence of invariable positions among specimens collected from
      each equid species or country. Conversely, two haplotypes were detected in horses
      from USA and in donkeys of Italy and Ukraine, respectively. The absence of
      haplotypes shared by the equid species suggests an affiliation of C. nassatus
      populations to their specific host. The results of the present study demonstrated
      that the characterization of mitochondrial regions may have important
      implications for studying the genetic structure and biology of equine
      cyathostomes, and to exploit taxonomic issues and practical implications related
      to the spread of anthelmintic resistance.

PMID- 18619737
TI  - Association between antibiotic use and changes in susceptibility patterns of
      Pseudomonas aeruginosa in an intensive care burn unit: a 5-year study, 2000-2004.
AB  - This study aimed to evaluate the relationship between antimicrobial resistance in
      Pseudomonas aeruginosa and annual antibiotic use in a burn unit. From 1 January
      2000 to 31 December 2004, 203 non-repetitive strains of Ps. aeruginosa were
      recovered from various clinical specimens. Antimicrobial susceptibility testing
      was performed using the disc diffusion method, and susceptibility data were
      interpreted according to break points recommended by the French Society of
      Microbiology. The antibiotic consumption for imipenem, ceftazidime, cefotaxime,
      piperacillin-tazobactam, ofloxacin, ciprofloxacin, gentamicin and amikacin was
      calculated with antimicrobial density. The relationship between antibiotic use
      and the resistance of Ps. aeruginosa was analysed. The consumption of ceftazidime
      and amikacin showed no association with resistance. A statistically significant
      relationship was observed between increasing use of ciprofloxacin and the
      incidence of resistant Ps. aeruginosa to this antibiotic (rs=0.89, p=0.05), and a
      significant correlation between ciprofloxacin consumption and resistance to
      imipenem was noted (rs=0.89, p=0.043). Restricted use of ciprofloxacin during
      2003 and 2004 was followed by a significant decrease of resistance in Ps.
      aeruginosa. Our report illustrates the major role of ciprofloxacin in the
      emergence of resistant Ps. aeruginosa.

PMID- 18619738
TI  - Cytidine-5-diphosphocholine supplement in early life induces stable increase in
      dendritic complexity of neurons in the somatosensory cortex of adult rats.
AB  - Cytidine-5-diphosphocholine (CDP-choline or citicholine) is an essential molecule
      that is required for biosynthesis of cell membranes. In adult humans it is used
      as a memory-enhancing drug for treatment of age-related dementia and
      cerebrovascular conditions. However the effect of CDP-choline on perinatal brain
      is not known. We administered CDP-choline to Long Evans rats each day from
      conception (maternal ingestion) to postnatal day 60 (P60). Pyramidal neurons from
      supragranular layers 2/3, granular layer 4 and infragranular layer 5 of
      somatosensory cortex were examined with Golgi-Cox staining at P240. CDP-choline
      treatment significantly increased length and branch points of apical and basal
      dendrites. Sholl analysis shows that the complexity of apical and basal dendrites
      of neurons is maximal in layers 2/3 and layer 5. In layer 4 significant increases
      were seen in basilar dendritic arborization. CDP-choline did not increase the
      number of primary basal dendrites on neurons in the somatosensory cortex. Primary
      cultures from somatosensory cortex were treated with CDP-choline to test its
      effect on neuronal survival. CDP-choline treatment neither enhanced the survival
      of neurons in culture nor increased the number of neurites. However significant
      increases in neurite length, branch points and total area occupied by the neurons
      were observed. We conclude that exogenous supplementation of CDP-choline during
      development causes stable changes in neuronal morphology. Significant increase in
      dendritic growth and branching of pyramidal neurons from the somatosensory cortex
      resulted in enlarging the surface area occupied by the neurons which we speculate
      will augment processing of sensory information.

PMID- 18619739
TI  - Alcohol outcome expectancies and drinking motives mediate the association between
      sensation seeking and alcohol use among adolescents.
AB  - Sensation seeking is a strong correlate of alcohol consumption among young
      people, yet the research on mediators of this association is mainly limited to
      English-speaking adolescents. The proposed model of the present study includes
      antecedent variables (sensation seeking, age and gender), mediators (positive and
      negative expectancies and drinking motives), and one outcome variable (a
      composite score of alcohol use). Self-reported data obtained from Hungarian high
      school students (N=707, mean age 16.6, SD=1.5) were analyzed with structural
      equation modeling. The general model fit was excellent, and this study supported
      the proposed sensation seeking --> positive and negative expectancies -->
      drinking motives --> alcohol use indirect effects. The total indirect effect
      explains 38% of sensation seeking and alcohol use association. Results support
      the notion that positive expectancy mediates between sensation seeking and
      drinking motives, and finally, positive expectancy and drinking motives are
      mediators between sensation seeking and alcohol use.

PMID- 18619740
TI  - Subjective alcohol effects and drinking behavior: the relative influence of early
      response and acquired tolerance.
AB  - OBJECTIVES: (1) To establish the reliability and validity of a modified version
      of the Self-Rating of Alcohol (SRE) form. (2) To differentiate early subjective
      alcohol response (SR) from acquired tolerance in the prediction of drinking
      outcomes. METHOD: 353 undergraduates completed an online survey. SR was assessed
      using the SRE form and a modified SRE including items assessing global stimulant
      and sedative effects. The Daily Drinking Questionnaire-Revised (DDQ-R), and the
      Rutgers Alcohol Problems Index (RAPI) assessed alcohol use and problems,
      respectively. RESULTS: The revised version of the SRE showed good internal
      consistency and incremental validity. Early SR assessed by the modified SRE was
      consistently associated with use and problems. Acquired tolerance was
      significantly related to use and problems above and beyond early SR. CONCLUSIONS:
      The modified SRE incorporating stimulant and sedative responses demonstrated good
      psychometric properties and the potential to capture unique variability in
      drinking outcomes. Differentiating early SR from tolerance showed that each
      contributes uniquely to drinking behavior and problems. Thus, future studies
      would benefit from examining the unique contribution of each aspect of SR.

PMID- 18619741
TI  - [Postpartum-urinary retention. A report of two cases and a review of literature].
AB  - The urinary retention is rather banal during the postpartum: 0.45 to 17.9% and
      now we know the main risk factors: duration of labour, epidural, episiotomy.
      Diagnosed on time, the postpartum-urinary retention will not have any
      consequence; on the other hand, a delay in care can lead to a persisting urinary
      retention with possible long-term urinary sequels. This article, based on two
      cases reports and a literature review, shows the heterogeneity in medical care of
      the postpartum-urinary retention.

PMID- 18619742
TI  - The dihydrouracil/uracil ratio in plasma, clinical and genetic analysis for
      screening of dihydropyrimidine dehydrogenase deficiency in colorectal cancer
      patients treated with 5-fluorouracil.
AB  - A rapid and cost-effective reversed phase high performance liquid chromatography
      (HPLC) method for quantification of dihydrouracil to uracil ratio (UH2/U) in
      plasma has been developed and used to screen for dihydropyrimidine dehydrogenase
      (DPD) deficiency in nine patients treated with 5-fluorouracil (5-FU). This HPLC
      method is based on the use of a simultaneous UV detection at 205 and 268nm during
      the analysis run of the plasma extract and taking into account the particularity
      that UH2 shows no absorbance response at 268nm. The plasma UH2/U ratio values
      evaluated by the use of our HPLC assay were found to be highly correlated with
      the plasma 5-FU-half-life values and were significantly associated with the toxic
      side effects, whereas, data set provided from genetic analysis of the coding
      sequences of the DPD gene (DPYD) were found to be insufficient to explain all the
      cases of the 5-FU-related toxicity pattern. The proposed HPLC assay could be
      available for routine clinical use for DPD deficiency assessment in patients
      prior to 5-FU administration.

PMID- 18619743
TI  - Helicobacter equorum is highly prevalent in foals.
AB  - Faecal samples of sixty-six 3-day- to 6-month-old foals were screened for
      Helicobacter equorum DNA by means of a PCR amplifying a 1074 bp fragment of the
      23S rRNA gene with primers specific for this enterohepatic Helicobacter species.
      H. equorum DNA was demonstrated in faeces from 28.6% of the less than 1-month-old
      foals, while 67.8% of foals from 1 to 6 months of age tested positive. In a
      previous study, H. equorum was demonstrated in faeces of 0.8-7.9% of adult
      horses. These results indicate that the prevalence of H. equorum in horses
      differs with the age of the investigated horse population. The organism seems
      highly prevalent in foals between 1 and 6 months of age but the possible
      association with intestinal disease in this age group needs further
      investigation.

PMID- 18619744
TI  - Evaluation of recombinant Bhlp29.7 as an ELISA antigen for detecting pig herds
      with swine dysentery.
AB  - Swine dysentery (SD) results from infection of the porcine large intestine with
      the anaerobic intestinal spirochaete Brachyspira hyodysenteriae. Diagnosis of SD
      traditionally has relied on detecting the spirochaete in the faeces of acutely
      affected pigs. To date simple and reliable serological assays that can be applied
      as a diagnostic tool at the herd level have not been available. In the current
      study a recombinant histidine tagged 29.7 kDa lipoprotein of B. hyodysenteriae
      (His6-Bhlp29.7) was used as an ELISA plate-coating antigen. Sera (n=1121) from
      slaughter-aged pigs on 19 farms were tested in this ELISA. Following optimization
      of the ELISA conditions using hyperimmune control sera, a set of 464 sera from
      slaughter-aged pigs from five herds where SD did not occur was tested. From these
      results a suitable cut-off value for herd negativity was defined as the mean
      optical density reading plus three standard deviations. Testing of 337 pig sera
      from six farms with SD then showed that the sensitivity of the test at the herd
      level was 100%, with all six farms having one or more serum samples exceeding the
      cut-off value for negativity. Finally, 320 sera from eight herds suspected of
      having SD were examined. Four of these herds were shown to have pigs with titres
      consistent with SD. The true health status of the other four herds that were
      serologically negative could not be confirmed. In conclusion, when used on sets
      of 40 sera from slaughter-aged pigs the His6-Bhlp29.7 ELISA as established proved
      to be a useful adjunct to the diagnosis of SD at the herd level.

PMID- 18619745
TI  - Long form of leptin receptor gene and protein expression in the porcine
      trophoblast and uterine tissues during early pregnancy and the oestrous cycle.
AB  - Leptin, the product of the OB gene, is a 16-kDa polypeptide of 146 amino acid
      residues produced mainly by adipocytes that regulates metabolism and
      reproduction. The actions of leptin are mediated mainly via the long form of the
      leptin receptor (OB-Rb). The identification of leptin and OB-Rb mRNAs and
      proteins in human and mouse endometrium, and placental trophoblast suggests that
      leptin may be involved in the implantation process. Thus, the aim of this study
      was to compare the expression levels of porcine OB-Rb mRNA and protein in the
      endometrium and myometrium during mid- and late-luteal phases of the oestrous
      cycle (days 10-12 and 14-16, respectively) as well as during two stages of
      pregnancy respondent to the beginning of the implantation process (days 14-16)
      and the post-implantation period (days 30-32), and in trophoblast during both
      periods of pregnancy. OB-Rb gene expression in endometrium during the examined
      stages of pregnancy and the mid- and late-luteal phases of the cycle was at the
      same level. In contrast, in myometrium leptin receptor gene expression decreased
      on days 14-16 of pregnancy compared to both phases of the cycle, and on days 30
      32 of pregnancy in relation to late-luteal phase. OB-Rb protein expression in the
      tissues was lower during the examined stages of pregnancy in comparison to the
      mid- and late-luteal phases of the cycle. In trophoblast, OB-Rb mRNA and protein
      expression was higher on days 30-32 than during days 14-16 of pregnancy. In
      conclusion, our results might suggest that leptin can participate in the control
      of pig reproduction by exercising its action at the uterine and trophoblast level
      and have a direct effect on these organ during both the luteal phase of the cycle
      and early pregnancy. Moreover, changes in OB-Rb gene and protein expression in
      tissues of pig reproductive tract strongly suggest that their sensitivity to
      leptin varies throughout luteal phase of the cycle and early pregnancy.

PMID- 18619746
TI  - Relationships between ovarian blood flow and ovarian response to eCG-treatment of
      dairy cows.
AB  - The goal of the present study was to investigate ovarian blood flow and ovarian
      response in cows undergoing a gonadotropin treatment to induce a superovulatory
      response, using transrectal colour Doppler sonography. Forty-two cows including
      19 cross-bred, 14 German Holstein and 9 German Black Pied cows were examined
      sonographically before hormonal stimulation on Day 10 of the oestrous cycle,
      three days after administration of eCG (Day 13) and seven days after artificial
      insemination (Day 7(p.i.)). After each Doppler examination, blood was collected
      for determination of total oestrogens (E) and progesterone (P4) in peripheral
      plasma. The blood flow volume (BFV) and pulsatility index (PI), which is a
      measure for blood flow resistance, were determined in the ovarian artery, and B
      mode sonography was used to count dominant follicles and corpora lutea. Important
      criteria to assess the ovarian response following the hormonal treatment were the
      number of follicles >5mm in diameter on Day 13 and the number of corpora lutea on
      Day 7(p.i.) per cow. The number of follicles ranged from 2 to 61 (mean+/-S.E.M.:
      17.5+/-1.7) and corpora lutea from 0 to 50 (mean+/-S.E.M.: 17.0+/-1.6). The BFV
      increased from 28.4 to 45.0 ml/min between Days 10 and 13 and reached a maximum
      of 108.5 ml/min on Day 7(p.i.) The PI decreased from 6.25 on Day 10 to 4.70 on
      Day 13 and to 2.10 on Day 7(p.i.) The BFV and PI on Day 13 did not correlate with
      the number of follicles (P>0.05). However, on Day 7(p.i.) the number of corpora
      lutea correlated positively with the BFV (r=0.64; P<0.0001), and an inverse
      relationship was found for the PI (r=-0.51; P=0.0005). There were no correlations
      (P>0.05) between the BFV and PI on Day 10 and the number of follicles on Day 13
      or the number of corpora lutea on Day 7(p.i.) Results of the present study show
      that in cows, a hormonal treatment to induce a superovulatory response yielded a
      marked increase in BFV and a marked decrease in PI in the ovarian artery.
      However, there was no correlation between BFV and PI in the ovarian arteries
      before hormonal stimulation and the number of follicles and corpora lutea that
      developed after stimulation. Thus BFV and PI measured in the ovarian arteries
      have limited diagnostic value to predict the outcome of a gonadotropin treatment.

PMID- 18619747
TI  - "Collision" metastasis from unknown primary squamous cell carcinoma and papillary
      microcarcinoma of thyroid presenting as lateral cervical cystic mass.
AB  - We report an unusual case of "collision metastasis". In a single lymph node, we
      found a metastatic mass composed of two immunohistochemically distinct components
      originating from two primary tumors: a papillary microfollicular thyroid cancer
      and an unknown primary squamous cell carcinoma. The clinical features and
      immunohistochemical profile are reported. Collision phenomena in oncology are
      extremely rare and pose diagnostic and management challenges which are discussed.

PMID- 18619748
TI  - [Pathophysiology and prognosis of refractory ascites in patients with cirrhosis].

PMID- 18619750
TI  - [Liver transplantation of refractory ascites].

PMID- 18619749
TI  - [Helminths and inflammatory bowel diseases].
AB  - The current etiologic model of inflammatory bowel diseases proposes a genetically
      predisposed host responding to a variety of environmental triggers by exhibiting
      an abnormal immune response to normal luminal flora. Crohn's disease is common in
      highly industrialized western countries where helminths are rare and uncommon in
      less developed areas of the world where most people carry worms. From this
      observation grew the hygiene hypothesis, which states that our failure to be
      exposed to previously common infectious agents alters the immune repertoire
      established in childhood. Helminths diminish immune responsiveness in naturally
      colonised humans and reduce inflammation in experimental colitis. Crohn's disease
      involves over reactive T-helper (Th1) pathways, and helminths blunt Th1
      responses, inducing production of Th2 cytokines. Helminths also induce regulatory
      T cells to maintain host mucosal homeostasis. Thus, there is an immunological
      basis to expect that exposure to helminths such as Trichuris suis will prove
      beneficial in Crohn's disease. Exposure to helminths may be effective in treating
      inflammatory bowel diseases and was well tolerated, according to the results of
      few studies. Its long-term safety remains unknown.

PMID- 18619751
TI  - Internal carotid artery stenosis measurements from 3D reconstructed multi
      directional views using phantom data set on MRA image sequence.
AB  - PURPOSE: To evaluate the inter-observer variability of stenosis measurements by
      using multi-directional 3D reconstructed projection view of internal carotid
      artery (ICA) that simulate the pre-determined stenosis degree on magnetic
      resonance angiography (MRA) image sequence of phantom data set and to compare the
      difference in measured percentages of maximum ICA stenosis between projection and
      axial images. MATERIALS AND METHODS: By using adaptive region growing and
      circumscribed quadrangle on the clinical data set, the cylinder shape of a
      mathematical phantom was modeled and implemented. The maximum ICA stenosis was
      categorized as mild (30%), moderate (50%), and severe (70%) stenosis those
      simulated on the tomographic image sequence of ICA only and synthesized phantom.
      The 36 maximum intensity projection (MIP) images were radially projected at 10
      degrees increments that were rotated about the long axis of the body by using the
      simulated stenosis degree on the tomographic image sequence of phantom data sets.
      The six different projection image data sets were used to measure the minimum
      residual lumen and reference diameter by three blinded observers. The percentage
      of maximum ICA stenosis was calculated as the following. The ICA stenosis grading
      was [1-(minimum residual lumen/averaged reference diameter)] x 100%. RESULTS: The
      percentage of maximum ICA stenosis degree measured on projection image was
      underestimated on ICA only phantom and overestimated on synthesized phantom
      compared to the simulated ICA stenosis degree on the axial image. In addition,
      the synthesized phantom provided the less projection image for stenosis
      measurement than ICA only phantom. These results attributed to the nature of MIP
      algorithm and the overlapping effects of surrounded anatomic structures such as
      other ICA, pair of external carotid artery (ECA), pair of VA, and background
      tissues. Furthermore, the inter-observer variability was also introduced by
      manual measurement. CONCLUSION: The automated scheme is recommended to measure
      the ICA stenosis by using axial image. This technique is not only accurate as
      possible but also robust, simple to handle, and less time consuming compared with
      manual measurements. A computerized ICA stenosis measuring method, which applied
      the image processing technique on the axial image, is necessary to overcome the
      drawbacks introduced by using the projection image and manual measurement.

PMID- 18619752
TI  - Assessment of regional left ventricular function by dual source computed
      tomography: interobserver variability and validation to laevocardiography.
AB  - OBJECTIVE: Assessment of left ventricular function is possible in contrast
      enhanced cardiac CT data sets. However, rapid ventricular motion especially in
      systole can lead to artifacts. Dual Source Computed Tomography (DSCT) has high
      temporal resolution which effectively limits motion artifact. We therefore
      assessed the accuracy of DSCT to detect regional left ventricular wall motion
      abnormalities in comparison to invasive cine angiocardiography. METHODS: We
      analyzed DSCT data sets of 50 patients (39 male, 11 female, mean age: 61+/-10
      years) which were acquired after intravenous injection of 55-70 mL contrast agent
      (rotation time: 330 ms, collimation: 2 mm x 64 mm x 0.6 mm, 120 kV, 380 mAs, ECG
      correlated tube current modulation). 10 data sets consisting of transaxial slices
      with a slice thickness of 1.5 mm, an increment of 1.0 mm and a matrix of 256 x
      256 pixels were reconstructed at 10 time instants during the cardiac cycle (0-90%
      in 10% increments). The data sets were analyzed visually by two independent
      readers, using standard left ventricular planes, concerning regional wall motion
      abnormalities. DSCT was verified in a blinded fashion against cine
      ventriculography performed during cardiac catheterization (RAO and LAO
      projection), using a 7-segment model. Analysis was performed on a per-patient
      (presence of at least one hypo-, a- or dyskinetic segment) and on a per-segment
      basis. RESULTS: Concerning the presence of a wall motion abnormality, the two
      observers agreed in 340/350 segments (97%) and 48/50 patients (96%). In invasive
      cine angiocardiography, 22 of 50 patients displayed at least one segment with
      abnormal contraction. To detect these patients, DSCT showed a sensitivity of 95%
      (21/22), specificity of 96% (27/28), positive predictive value of 95% and
      negative predictive value of 96%. Out of a total of 350 left ventricular
      segments, 66 segments had abnormal contraction in cine angiocardiography (34
      hypokinetic, 26 akinetic, 6 dyskinetic). For detection of these segments, DSCT
      had a sensitivity of 88% (58/66), specificity of 98% (278/284), positive
      predictive value of 91% (58/64) and negative predictive value of 97% (278/286).
      CONCLUSION: DSCT allows the detection of regional wall motion abnormalities with
      high interobserver agreement as well as high sensitivity and specificity. Whereas
      sensitivity and positive predictive value were higher in a per-patient- in
      comparison to a per-segment-based analysis, specificity, negative predictive
      value and interobserver agreement did not differ considerably between both
      analyzing methods.

PMID- 18619753
TI  - MR fetography using heavily T2-weighted sequences: comparison of thin- and thick
      slab acquisitions.
AB  - PURPOSE: To evaluate the use of MR-fetography sequences in identifying the major
      fetal structures and to compare thick- and thin-slab acquisitions for their
      diagnostic value. MATERIALS AND METHODS: Twenty-one consecutive, pregnant women
      with suspected fetal pathology underwent fetal magnetic resonance imaging (MRI)
      using a 1.5 T MRI unit. Heavily T2-weighted, single-shot fast spin-echo (SSFSE)
      sequences with a long echo train (MR-fetography) were acquired in a thick- and
      thin-slab modus. Thick- and thin-slab acquisitions were reviewed by two
      experienced radiologists with regard to the overall image quality and landmark
      anatomical structures (spinal canal, spinal cord, posterior fossa, cerebellum,
      brainstem, basal cisterns, stomach, urinary bladder and umbilical cord according
      to a three-scale grading system (good, moderate and poor). Visibility scores were
      calculated and compared between both sequences. RESULTS: Overall image quality
      was graded good in 76.2%, moderate in 19.0% and poor in 4.8% for thick-slab
      images and good in 81%, moderate in 14.3% and poor in 4.8% for thin-slab images.
      The visibility scores of the thick/thin-slab images for evaluation of the main
      fetal structures were as follows: for the spinal canal 2.8+/-0.4/2.9+/-0.54
      (p>0.05), spinal cord 2.4+/-0.75/2.7+/-0.66 (p>0.05), posterior fossa components
      (cerebellum, brainstem and basal cisterns) 2.4+/-0.68/2.8+/-0.54; 2.4+/
      0.67/2.7+/-0.66; 2.5+/-0.51/2.7+/-0.56 (p<0.05), stomach 2.8+/-0.44/2.9+/-0.48
      (p>0.05), urinary bladder 2.8+/-0.51/2.8+/-0.54 (p>0.05) and umbilical cord 2.9+/
      0.30/2.6+/-0.60 (p<0.05). CONCLUSION: Heavily T2-weighted MR-fetography renders a
      quick overview of fetal contours, fetal position, amount of amniotic fluid and
      integrity and presence of several major fluid containing structures. Thick- and
      thin-slab acquisitions render complementary information. Thick-slab images
      display the entire fetus in one projection while thin-slab images provide more
      detailed anatomical information. The short imaging time usually allows measuring
      both thick- and thin-slab images. MR-fetography is as a helpful addition to
      conventional fetal MRI. MR-fetography should not be viewed as a single, stand
      alone sequence but as a supporting fast MR sequence in a well-designed
      multisequence fetal MRI protocol. Future studies evaluating larger patient groups
      are mandatory.

PMID- 18619754
TI  - Region of interest and pixel-by-pixel analysis of dynamic contrast enhanced
      magnetic resonance imaging parameters and time-intensity curve shapes: a
      comparison in chondroid tumors.
AB  - Dynamic contrast enhanced (DCE) MRI is widely acknowledged to be a helpful tool
      in the diagnosis and differentiation of tumors. In common clinical settings, the
      dynamic changes described by the time-intensity curves (TICs) are evaluated to
      find patterns of atypical tissue behavior, i.e., areas characterized by rapid
      contrast wash-in and wash-out. Despite the ease of this approach, there is no
      consensus about the specificity of the TIC shapes in discriminating tumor grades.
      We explore a new way of looking at TICs, where these are not averaged over a
      selected region of interest (ROI), but rendered pixel-by-pixel. In this way, the
      characteristic of the tissue is not given as a single TIC classification but as a
      distribution of the different TIC patterns. We applied this method in a group of
      patients with chondroid tumors and compared its outcome with the outcome of the
      standard ROI-based averaged TIC analysis. Furthermore, we focused on the problem
      of ROI selection in these tumors and how this affects the outcome of the TIC
      analysis. Finally, we investigated what relationship exists between the
      "standard" DCE-MRI parameter maximum enhancement (ME) and the TIC shape.
      CONCLUSIONS: We demonstrate that, where the ROI approach fails to show the
      presence of areas of rapid contrast wash-in and wash-out, the pixel-by-pixel
      approach reveals the coexistence of a heterogeneous pattern of TIC shapes.
      Secondly, we point out the differences in the DCE MRI parameters and tumor volume
      that can result when selecting the tumor based on DCE parameter maps or post
      contrast T1-weighted images. Finally, we show that ME maps and TIC shape maps
      highlight different tissue areas and, therefore, the use of the ME maps is not
      appropriate for the correct identification of areas of atypical TICs.

PMID- 18619755
TI  - A combined harmonic phase and strain-encoded pulse sequence for measuring three
      dimensional strain.
AB  - Measurement of myocardial strain provides direct information about heart function
      that can be correlated with disease. We present an MRI pulse sequence that
      acquires in just six heartbeats both harmonic phase (HARP) and strain-encoded
      (SENC) images and provides dense measurements of radial, circumferential and
      longitudinal strains within a single short-axis slice. Normal volunteer data
      confirm the feasibility of this pulse sequence, and acquired data demonstrate the
      strain measurement reliability.

PMID- 18619756
TI  - Quenching of alpha,beta-unsaturated aldehydes by green tea polyphenols: HPLC-ESI
      MS/MS studies.
AB  - The aim of this work was to investigate in vitro the quenching activity of green
      tea polyphenols against alpha,beta-unsaturated aldehyde, using 4-hydroxy-nonenal
      (HNE) as prototype and HPLC-ESI-MS/MS techniques. HNE is the most abundant and
      genotoxic product of oxidation of dietary polyunsaturated fatty acids, and is
      believed to be involved in the early stage of colorectal carcinogenesis on
      account of its genotoxic potential. Both epigallocatechin gallate (EGCG, 1.0
      3.5mM), the main constituent of green tea polyphenols, and a green tea aqueous
      extract are able to quench HNE (50 microM) in colorectal physiomimetic conditions
      (10mM phosphate buffer, pH 8.0, 37 degrees C), giving rise to the formation of
      six diastereomeric covalent adducts at the ring A of EGCG, as indicated by their
      ESI-MS/MS fragmentation pathways. The specificity of the adduction positions was
      explained by (1)H NMR experiments. HNE quenching is pH-dependent and maximum at
      pH 8.0. ESI-MS analysis showed no formation of 4-hydroxy-2,3-epoxy-nonanal, or
      adduction of the epoxide to EGCG. This implies that too little hydrogen peroxide
      (1mM, 24h incubation, FOX-2 method) develops from auto-oxidation of EGCG in our
      aerobic experimental conditions to oxidize HNE to its corresponding epoxide, so
      this mechanism is not responsible for the compound's disappearance. EGCG and
      green tea extract also quenched acrolein, another genotoxic alpha,beta
      unsaturated aldehyde, giving one predominant adduct and minor isobaric species,
      probably due the adduction of acrolein at different positions of the EGCG ring A.
      These results suggest that EGCG and green tea extract, beside the proposed
      mechanisms of chemoprevention that target multiple cell-signaling pathways that
      control cell proliferation and apoptosis in cancer cells, can also prevent
      protein carbonylation in the tumor tissue environment, depending on the pH of the
      medium surrounding the tissue, the type of tumor, the stage of dysregulation of
      lipid peroxidation and, finally, the stage of carcinoma development.

PMID- 18619757
TI  - Robust Raman measurement of hydrogen peroxide directly through plastic containers
      under the change of bottle position and its long-term prediction reproducibility.
AB  - Hydrogen peroxide concentration in antiseptic solutions has been non
      destructively measured with the use of wide area illumination (WAI) scheme by
      applying a laser beam directly through a plastic container. The prediction
      accuracy was comparable to that from the use of quartz cell instead of a plastic
      bottle as well as near-infrared (NIR) prediction result in the previous study.
      Although the position of a plastic bottle was artificially changed in three
      dimensional directions up to +/-10 mm to simulate real situation of practical
      measurement, the prediction accuracy was not degraded within +/-5 mm positional
      variation. This robust prediction performance was powered by the merits of WAI
      scheme that could provide improved reproducibility by illuminating large sample
      areas as well as less sensitivity of sample placement by the design of long focal
      length. Moreover, the prediction accuracy was successfully maintained over a long
      period of time. Finally, the prediction was also reproducible under the situation
      of laser power variation. The overall results demonstrate that WAI Raman scheme
      can provide robust and non-destructive quantitative analysis for not only
      hydrogen peroxide in antiseptic solution, but also other active pharmaceutical
      ingredients in diverse containers.

PMID- 18619758
TI  - Antifouling enzymes and the biochemistry of marine settlement.
AB  - Antifouling coatings are used extensively on marine vessels and constructions,
      but unfortunately they are found to pose a threat to the marine environment,
      notably due to content of metal-based biocides. Enzymes have repeatedly been
      proposed as an alternative to traditional antifouling compounds. In this review,
      the enzymes claimed to hold antifouling activity are classified according to
      catalytic functions. The enzyme functions are juxtaposed with the current
      knowledge about the chemistry of settlement and adhesion of fouling organisms.
      Specific focus will be on bacteria, microalgae, invertebrate larvae and
      macroalgae zoospores. Two main concepts in enzyme-based antifouling are
      identified: breakdown of adhesive components and catalytic production of
      repellent compounds in-situ. The validity of the various modes of action is
      evaluated and the groups of enzymes with the highest potential are highlighted.

PMID- 18619759
TI  - "Four Habits" goes abroad: report from a pilot study in Norway.
AB  - OBJECTIVE: "Four Habits" is the first larger generic clinical communication
      program to have a documented effect. It has not been evaluated outside USA. In a
      pilot study, Norwegian hospital physicians assessed its usefulness, and we
      developed a questionnaire where patients reported "Four Habits"-specific
      physician behaviour. METHODS: We ran a 3-day course with 16 participants and
      three US facilitators. The questionnaire mapping "Four Habits" with 23 items was
      distributed by participating physicians to 210 patients. Participating physicians
      met in evaluative focus groups 3 months after the course. RESULTS: The
      questionnaire was condensed to 10 items after factorial analysis. The resulting
      scale performed well. A large amount of missing data on some items suggested that
      patients found it difficult to evaluate details of "Four Habits"-specific
      physician behaviour. Participants found that the "Four Habits" short course led
      to improvement of their encounters. Some elements of the method were not
      perceived as relevant for all types of encounters (habits II and III).
      CONCLUSION: "Four Habits" is applicable outside US with some adjustments. A
      shortened version of the questionnaire will be used in a planned randomized
      controlled trial.

PMID- 18619760
TI  - The role of relationships in the professional formation of physicians: case
      report and illustration of an elicitation technique.
AB  - OBJECTIVE: Studies of physicians' professional development highlight the
      important effect that the learning environment has in shaping student attitudes,
      behaviors, and values. The objective of this study was to better understand the
      interplay among relationships and experiences in mediating the effects of the
      learning environment. METHODS: We randomly recruited 2nd- and 4th-year students
      from among volunteers at each of five medical schools. One interviewer at each
      school conducted a face-to-face, open-ended, semi-structured interview with each
      student. The interviewers used a method called 'life-circle diagramming' to
      direct the student to draw a picture of all of the relationships in his/her life
      that had an influence on the sort of doctor that each student saw him/herself
      becoming. Interviews lasted between 60 and 120 min. Using a narrative framework
      that focuses on elements of students' stories (e.g., setting, characters, plot),
      we analyzed transcripts through an iterative process of individual reading and
      group discussion to derive themes and relationships among themes. RESULTS: Twenty
      students completed interviews. These students are embedded in complex webs of
      relationships with colleagues, friends, family, role models, patients, and
      others. Most students entered medical school with formed notions of what they
      wanted to 'be like' as physicians. While students generally gravitated toward
      relationships with like-minded people, their experiences varied, and some
      students could sense themselves changing as they moved through school. Such
      changes were often related to important events or issues. The relationships that
      students found themselves in during the context of these events had an important
      effect on students' beliefs about what kinds of behaviors and attitudes were
      possible and desirable in their future practice. CONCLUSIONS: Students proceed
      through medical school embedded in complex webs of relationships that exert a
      powerful influence (both positive and negative) on their formation as physicians.
      PRACTICE IMPLICATIONS: Educational interventions that foster adoption of
      professional values need to acknowledge the influence of relationships, and
      assist students to harness and shape relational effects on their growth and
      development. The life-circle diagramming activity holds potential to promote
      reflection and self-knowledge, and to provide a foundation for professional
      growth.

PMID- 18619761
TI  - Trends in colorectal cancer testing among Medicare subpopulations.
AB  - BACKGROUND: In 1998, Medicare initiated universal coverage for colorectal cancer
      (CRC) screening via fecal occult blood testing (FOBT) and sigmoidoscopy. In mid
      2001, universal coverage was advanced to screening colonoscopy. This study sought
      to determine whether trends in CRC testing differed among racial/ethnic, age, or
      gender subgroups of the Medicare population. METHODS: In 2006, claims from 1995
      to 2003 were analyzed for annual 5% random samples of fee-for-service Medicare
      enrollees living in Surveillance, Epidemiology, and End Results (SEER) regions to
      calculate the annual, age-standardized percentages of subjects who received FOBT,
      sigmoidoscopy, or colonoscopy. Logistic regression then modeled trends in annual
      test use within racial/ethnic, age, and gender subgroups across three Medicare
      coverage periods (precoverage [1995-1997]; limited coverage [1998-mid-2001]; and
      full coverage [mid-2001-2003]). RESULTS: The annual use of FOBT and sigmoidoscopy
      declined from 1995 to 2003 in all racial/ethnic groups, but the relative decline
      in sigmoidoscopy use was greater among whites compared to nonwhites. In contrast,
      colonoscopy use increased substantially in all racial/ethnic groups. However,
      relative to the precoverage period among whites, the full-coverage period was
      associated with significantly greater colonoscopy use among whites (OR=2.14; 95%
      CI=2.09, 2.19) than blacks (OR=1.86; 95% CI=1.75, 1.96); Asian/Pacific Islanders
      (OR=1.73; 95% CI=1.62, 1.86); or Hispanics (OR=1.65; 95% CI=1.49, 1.81). The use
      of colonoscopy during the full-coverage period was also differentially greater
      among enrollees aged <80 years. CRC testing trends were similar among male and
      female enrollees. CONCLUSIONS: Colonoscopy is supplanting sigmoidoscopy as a CRC
      test among Medicare enrollees, while FOBT use is in decline. The transition from
      sigmoidoscopy to colonoscopy has occurred more quickly among white than nonwhite
      Medicare enrollees.

PMID- 18619762
TI  - [Sedation and analgesia for the brain-injured patient].
AB  - Sedation-analgesia occupies an essential place in the specific therapeutic
      arsenal of the brain-injured patients. The maintenance of the perfusion of the
      brain, its relaxation and its protection are the fundamental objectives whose
      finality is to avoid the extension of the lesions and to preserve the neuronal
      capital. Sedation is instituted when patients are severely agitated or present a
      deterioration of their state of consciousness (GCS< or =8). Under cover of
      mechanical ventilation, sedation is the first line treatment of intracranial
      hypertension, a common pathway of various acute brain diseases of traumatic,
      vascular or other origin. The use of the combination of hypnotic and opioids is
      the rule. The combined action of these two classes reinforces and improves their
      sedative effects. Midazolam is the 2 benzodiazepine of reference. Propofol is
      more and more frequently added to the combination of hypnotic and opioids. The
      "propofol infusion syndrome" is a severe limitation to its long term
      administration in particular among patients presenting a severe septic or
      inflammatory state. Propofol will be imperatively stopped in the event of
      metabolic acidosis, rhabdomyolysis, acute renal insufficiency, hyperkaliemia or
      increase in the blood triglyceride levels. The use of thiopental is restricted to
      the most severe cases. Its use as a monotherapy at high doses is abandoned to the
      profit of a co-administration with midazolam or even with the combination of
      midazolam and propofol. Thiopental overdose is very frequent in the event of
      associated hypothermia. Etomidate does not have its place apart from induction in
      fast sequence. The neuro-protective effects of ketamine require to be
      demonstrated in man before being recommended routinely. Withdrawal of sedation
      can be responsible for a state of agitation which can be controlled by
      neuroleptics.

PMID- 18619763
TI  - Interaction of pneumococcal phase variation and middle ear pressure/gas
      composition: an in vitro model of simulated otitis media.
AB  - Streptococcus pneumoniae, a leading cause of otitis media (OM), undergoes
      spontaneous intra-strain variations in colony morphology. Transparent (T) variant
      is more efficient in colonizing the nasopharynx while the opaque (O) variant
      exhibits greater virulence during systemic infections. We hypothesized that
      changes in middle ear (ME) gas pressure/composition during Eustachian tube (ET)
      dysfunction and the treatment of that dysfunction, e.g., tympanostomy tube (TT)
      insertion, play a role in selecting the S. pneumoniae variant that can
      efficiently colonize/infect the ME mucosa. Human ME epithelial cells were
      preconditioned for 24h under one of three conditions that simulated (1) normal
      ME, (2) ME with ET obstruction (ETO) and (3) ME with TT; subsequently exposed to
      a dose (approximately 10(7)CFU/ml) of either T or O variant of S. pneumoniae, and
      then incubated for 1h and 3h. Under the simulated ETO and TT conditions, T
      variant exhibited a higher growth rate and greater epithelial adherence and
      killing than did O variants. Attachment of T variant to epithelial cells was
      documented by scanning electron microscopy. These results suggest that the T
      variant is more highly adapted to various ME environments than the O variants.

PMID- 18619764
TI  - Symptoms associated with malignant wounds: a prospective case series.
AB  - A significant proportion of cancer patients develop malignant wounds. Malignant
      wounds are generally nonhealable and are managed with palliative methods.
      Palliative wound care encompasses the pain and symptom management of such wounds.
      Sixty-seven of 472 cancer patients from a prospective sequential case series of
      palliative medicine consultations demonstrated malignant wounds at the time of
      referral and were studied to determine the most common symptoms and anatomic
      sites associated with malignant wounds. Data were collected from patients' own
      reports of up to three wound-related symptoms. Overall, 67.7% of malignant wounds
      were associated with at least one of the following eight symptoms: pain, mass
      effect, esthetic distress, exudation, odor, pruritus, bleeding, and crusting;
      21.9% of wounds were associated with two or more symptoms; and 11.5% of wounds
      were associated with three symptoms. The symptom point prevalence was 31.3% for
      pain, 23.9% for mass effect, 19.4% for esthetic distress, 17.9% for exudation,
      11.9% for odor, 6% for pruritus, 6% for bleeding, and 1.5% for crusting. Breast
      cancer patients had the highest prevalence of malignant wounds (47.1%). The
      anterior chest wall and breast was the site of 31.2% of wounds. The perineum and
      genitalia presented with the highest ratio of symptoms per wound (2.2). The
      results of this study reflect that malignant wounds are associated with a
      significant symptomatic burden, and reinforces the need for thorough clinical
      assessment and evaluation of symptoms. Further research is required to define the
      optimal methods of pain and symptom management for malignant wounds.

PMID- 18619765
TI  - Re: Chiropractic: a critical evaluation.

PMID- 18619766
TI  - Pain and quality of life in hospitalized patients with heart failure.
AB  - The pain experience of patients with heart failure (HF) and its impact on their
      quality of life (QOL) has not been described in sufficient detail. This study
      sampled patients hospitalized with HF to describe the prevalence and severity of
      bodily pain; evaluate differences in bodily pain related to selected demographic
      and disease-specific characteristics; and evaluate the effect of selected
      demographic, disease-specific characteristics, bodily pain, and mental health on
      QOL. Two items from the Medical Outcomes Study--Short Form (SF-36) were used to
      measure pain, and one subscale of the SF-36 was used to evaluate mental health.
      The Minnesota Living With Heart Failure Questionnaire was used to measure QOL.
      Patients with HF (n=93) had a mean age of 75 years, were predominantly male
      (65%), and lived alone (47.3%). Lung diseases and diabetes were the most common
      comorbidities; 58% were categorized as New York Heart Association (NYHA) Class
      III, whereas 58% of the sample was diagnosed with HF in the past four years. Of
      note, 85% of the patients reported pain and 42.5% said that it was in the severe
      or very severe range. No demographic variables were associated with pain, whereas
      a higher number of chronic conditions were associated with pain. SF-36 mental
      health and pain scores, as well as NYHA class, explained 34.1% of the variance in
      QOL in patients with HF. These data suggest that pain is highly prevalent and has
      a significant impact on the QOL of patients with HF. However, additional research
      is warranted to determine the specific causes and characteristics of pain in
      these patients.

PMID- 18619767
TI  - A first step in the development of an international self-report instrument for
      physical functioning in palliative cancer care: a systematic literature review
      and an expert opinion evaluation study.
AB  - Decline in physical functioning (PF) in progressive cancer increases risk of
      psychological problems, dependence, and distress, and it considerably affects
      quality of life. Despite this, assessment of PF has received little attention.
      Standardized, internationally endorsed assessment tools are needed that assess
      activities of relevance to palliative cancer patients from very low to high
      levels of PF. This study was done in cooperation with the European Association
      for Palliative Care Research Network. It was initiated to develop a computer
      based symptom-assessment tool and aimed to 1) identify relevant existing PF
      assessment instruments, 2) extract relevant items and classify them into
      meaningful subdimensions, and 3) construct unidimensional scales of selected PF
      domains. A systematic literature review was performed to detect relevant PF items
      from existing instruments. The International Classification of Functioning and
      Health was used to decide relevant subdimensions of PF, and expert panels within
      palliative cancer care were consulted to make decisions on activities to be
      included. One hundred and thirty-five instruments containing 743 items were
      included from the literature review. Two relevant PF subdimensions were revealed:
      Mobility (386 items representing 65 different activities) and Self-Care (143
      items representing 30 different activities). The final PF tool consisted of two
      unidimensional scales: 24 hierarchically ranked Mobility items ranging from
      turning in bed to running, and 16 non-hierarchically ranked Self-Care items.
      Further testing of the instrument in a palliative cancer population is needed to
      develop the final PF instrument.

PMID- 18619768
TI  - Epidemiology of regular prescribed opioid use: results from a national,
      population-based survey.
AB  - Chronic pain occurs commonly and accounts for significant suffering and costs.
      Although use of opioids for treatment of chronic pain is increasing, little is
      known about patients who use opioids regularly. We report data from the second
      wave of the Healthcare for Communities survey (2000-2001), a large, nationally
      representative household survey. We compared regular users of prescription
      opioids to nonusers of opioids and calculated the percentage of individuals
      within a given demographic or disease state that reported chronic opioid use.
      Approximately 2% of the 7,909 survey respondents reported use of opioid
      medications for at least a month, which the Healthcare for Communities survey
      defined as "regular use." Opioid users were more likely than nonusers to report
      high levels of pain interference with their daily lives and to rate their health
      as fair or poor. Arthritis and back pain were the most prevalent chronic,
      physical health conditions among users of opioids, with 63% of regular users of
      opioids reporting arthritis and 59% reporting back pain. The majority of regular
      users of opioids had multiple pain conditions (mean=1.9 pain conditions). Regular
      opioid users appear to have an overall lower level of health status and to have
      multiple, chronic physical health disorders.

PMID- 18619770
TI  - Obsessive beliefs in first-degree relatives of patients with OCD: a test of the
      cognitive vulnerability model.
AB  - Cognitive models of obsessive-compulsive disorder (OCD) focus on the role of
      dysfunctional beliefs and appraisals in conferring risk to the onset and
      persistence of clinical obsessions. The origins of obsessive beliefs have been
      proposed to occur within a familial-based developmental context, although little
      research has examined this empirically. The aim of the present study was to
      examine the familial cognitive vulnerability for OCD by comparing scores on the
      Obsessive Beliefs Questionnaire (OBQ) [Obsessive Compulsive Cognitions Working
      Group (2005). Psychometric validation of the obsessive beliefs questionnaire and
      interpretation of intrusions inventory-Part 2. Factor analyses and testing of a
      brief version. Behavior Research and Therapy, 43, 1527-1542] between DSM-IV
      diagnosed OCD probands, their nonaffected first-degree relatives, and nonaffected
      controls. First-degree relatives scored significantly higher than controls on the
      OBQ domain tapping inflated responsibility and overestimation of threat. Further,
      relatives of early onset OCD probands scored significantly higher than controls
      on both the inflated responsibility and overestimation of threat domain and the
      domain tapping perfectionism and intolerance of uncertainty. The results are
      discussed in relation to the developmental context of cognitive-based
      vulnerabilities for OCD.

PMID- 18619769
TI  - Do interference-based cut-points differentiate mild, moderate, and severe levels
      of 16 cancer-related symptoms over time?
AB  - In our previous work, we established interference-based cut-points to
      differentiate moderate from mild, and severe from moderate levels of severity for
      16 symptoms as reported by cancer patients undergoing chemotherapy. This work
      examines how consistent the differentiation is over time. If the levels of
      severity successfully differentiate interference scores over time, then anchor
      based categories can be developed to evaluate patients' responses to the
      intervention. To test the differentiation of the interference scores by the three
      severity categories, data from two symptom management trials were used. Five
      hundred and ninety-nine patients were queried at each of the six contacts that
      occurred over eight weeks as to the severity of each of the 16 symptoms on the
      scale from 0 (not present) to 10 and the extent to which each symptom interfered
      with enjoyment of life, relationships with others, general daily activities and
      emotions. Longitudinal models that related interference scores to severity levels
      of symptoms were used. Differences among adjusted mean interference scores for
      mild, moderate, and severe levels were tested at each contact. Differences among
      interference-based severity categories were consistent over time and clinically
      important, and thus can be used to anchor changes in symptom severity.

PMID- 18619771
TI  - Gene-rich islands for fiber development in the cotton genome.
AB  - Cotton fiber is an economically important seed trichome and the world's leading
      natural fiber used in the manufacture of textiles. As a step toward elucidating
      the genomic organization and distribution of gene networks responsible for cotton
      fiber development, we investigated the distribution of fiber genes in the cotton
      genome. Results revealed the presence of gene-rich islands for fiber genes with a
      biased distribution in the tetraploid cotton (Gossypium hirsutum L.) genome that
      was also linked to discrete fiber developmental stages based on expression
      profiles. There were 3 fiber gene-rich islands associated with fiber initiation
      on chromosome 5, 3 islands for the early to middle elongation stage on chromosome
      10, 3 islands for the middle to late elongation stage on chromosome 14, and 1
      island on chromosome 15 for secondary cell wall deposition, for a total of 10
      fiber gene-rich islands. Clustering of functionally related gene clusters in the
      cotton genome displaying similar transcriptional regulation indicates an
      organizational hierarchy with significant implications for the genetic
      enhancement of particular fiber quality traits. The relationship between gene
      island distribution and functional expression profiling suggests for the first
      time the existence of functional coupling gene clusters in the cotton genome.

PMID- 18619772
TI  - Inflammatory markers and negative mood symptoms following exercise withdrawal.
AB  - OBJECTIVE: Physical inactivity is associated with elevated inflammatory markers,
      but little is known about the time trajectories of reduced physical activity and
      inflammatory markers. Changes in inflammatory markers in response to withholding
      regular aerobic exercise were prospectively examined and correlated with
      increased negative mood symptoms and fatigue that accompany exercise withdrawal.
      METHODS: Participants with regular exercise habits (N=40, mean age of 31.3+/-7.5
      years, 55% women) were randomized to aerobic exercise withdrawal or to continue
      regular exercise for 2 weeks. Protocol adherence was documented using ambulatory
      actigraphy. Inflammatory markers (interleukin-6, C-reactive protein, fibrinogen
      and soluble intercellular adhesion molecule-1) were assessed at weekly intervals.
      Negative mood was measured with the Profile of Mood States (POMS) and the Beck
      Depression Inventory (BDI), and fatigue with the Multidimensional Fatigue
      Inventory (MFI). Autonomic nervous system activity was examined using heart rate
      variability-based indices. RESULTS: Changes in inflammatory markers did not
      differ between exercise withdrawal and control groups (multivariate p
      interaction=0.25). Exercise withdrawal resulted in increased negative mood
      symptoms and fatigue from baseline to day 14 compared to controls (p
      DeltaPOMS=0.008, p DeltaBDI=0.002; p DeltaMFI=0.003), but these responses were
      not associated with changes in inflammatory markers (p-values >0.10).
      Inflammatory markers were also not correlated with autonomic nervous system
      dysregulation (p-values >0.10). CONCLUSION: Inflammatory markers were not
      increased following 2 weeks of exercise withdrawal. Negative mood symptoms and
      fatigue were not accounted for by changes in inflammatory markers. Compensatory
      feedback mechanisms may operate among healthy individuals to promote resilience
      from the effects of reduced exercise.

PMID- 18619773
TI  - Endovenous laser ablation for short saphenous vein incompetence.
AB  - Conventional surgery for short saphenous vein (SSV) incompetence has a high
      incidence of recurrence and is associated with neurovascular injury. The aim of
      this study was to evaluate the safety and efficacy of endovenous laser ablation
      (EVLA) as an alternative to open surgery for SSV incompetence. Data were
      prospectively collected for all patients undergoing EVLA for SSV disease in our
      unit, including clinical outcomes and postoperative duplex. There were 368 EVLA
      procedures performed from April 2004 through December 2007, of which 66 (18%)
      were for SSV incompetence. Six (9%) SSV procedures were for recurrent disease
      after conventional surgery. Forty (61%) procedures were performed under local
      anesthesia, including four patients who underwent bilateral procedures at the
      same session. There were no intraoperative complications, and there was no
      evidence of neurovascular injury. During a median follow-up of 14 months
      (interquartile range 6-24) there was no clinical or duplex evidence of recurrence
      and no recanalization of the SSV. Our early results suggest that EVLA is a safe
      alternative to conventional surgery for the treatment of SSV incompetence in
      patients with C2-C4 disease. Bilateral procedures have been performed under local
      anesthesia.

PMID- 18619774
TI  - Optional filters in trauma patients: can retrieval rates be improved?
AB  - Prophylactic inferior vena cava interruption may be appropriate in trauma
      patients at risk for pulmonary embolism for whom anticoagulation is
      contraindicated. The Recovery filter is approved for removal up to 180 days from
      insertion. High retrieval rates need to be achieved before we can lower the
      threshold for inserting these filters prophylactically. The objective of this
      study was to evaluate the retrieval rate of the Recovery filter in this patient
      population and how it has influenced our practice. This is a retrospective study
      in which the records of 122 consecutive trauma patients in whom the Recovery
      filters were inserted between October 2003 and October 2005 were reviewed.
      Patients who had the new generation of this filter were excluded. All these
      filters were inserted with the intention of retrieval. We attempted to contact
      all these patients at 3 months. The technical factors associated with failure to
      retrieve these filters were reviewed. There were no complications related to
      filter insertion. Excluding six patients (4.9%) who expired from causes unrelated
      to the insertion procedure, 20 patients could not be reached (17.3%) and 21
      patients declined retrieval (18.1%). The filters were considered permanent in 18
      patients (15.5%) if they were not ambulatory or if they developed inferior vena
      cava occlusion. Inferior vena cava occlusion was diagnosed in four patients
      (5.5%). Seventy-three (62.9%) patients presented for follow-up and were evaluated
      by color venous duplex ultrasound. We attempted to retrieve the filters in 52
      patients and were successful in 45 (86.5%). However, the total retrieval rate was
      40.5%. All failures of retrieval were related to tilting of the filters or
      bending of the limbs. There were no complications related to the retrieval
      procedure. Insertion and retrieval of the Recovery inferior vena cava filter are
      safe. In spite of the thorough follow-up and the good success rate in retrieving
      the filters, the overall retrieval rate in this patient population is still low.
      This should be strongly considered at the time of insertion. Multiple factors
      were found to contribute. Attention to details in patient selection and follow-up
      as well as modifications in technique may improve the retrieval rate.

PMID- 18619775
TI  - Endovascular dialysis interventions in the era of DOQI.
AB  - The National Kidney Foundation Dialysis Outcomes and Quality Initiative (DOQI)
      recommends autogenous fistulae as the preferred access for new dialysis
      procedures. Unfortunately, despite superior patency rates compared to prosthetic
      grafts, even autogenous access durability is often undermined by venous stenosis
      due to intimal hyperplasia at the outflow vein or by central venous stenosis due
      to long-standing central venous catheters. Salvage interventions, in the form of
      endovascular treatments such as percutaneous transluminal angioplasty (PTA)
      and/or stenting, are increasingly utilized for access salvage and maintenance.
      The objective of this study was to evaluate the efficacy of endovascular dialysis
      interventions in the era of DOQI. A retrospective review of a database of
      endovascular interventions for dialysis access during 36 months at an academic
      medical center was performed. Both central venous and access outflow lesions were
      included in the analysis. Kaplan-Meier curves and log-rank analysis were used to
      assess and compare time-dependent variables. Forty-five patients with dialysis
      access underwent 72 endovascular interventions for access maintenance. There were
      27 central venous and 32 outflow endovascular interventions with 98% follow-up.
      Primary and assisted primary patency rates for outflow balloon PTA were 50% and
      72% at 12 months, respectively. There were 1.1 reinterventions required per index
      outflow PTA procedure. Postintervention primary patency rates for central venous
      PTA were 30% and 9% at 6 and 12 months, respectively. Postintervention assisted
      patency for central venous PTA was 100% at 12 months, requiring 1.8
      reinterventions per index PTA. Central venous and venous outflow interventions
      extended overall access patency by 38.5 and 33 months, respectively (p < 0.0001).
      Endovascular interventions are the mainstay of treatment for the malfunctioning
      dialysis access. Despite the need for multiple reinterventions and close
      surveillance, catheter-based interventions positively contribute to dialysis
      access durability in accordance with DOQI guidelines.

PMID- 18619776
TI  - Complete femoral artery and vein avulsion from a hyperextension injury: a case
      report and literature review.
AB  - Blunt peripheral extremity vascular injuries are much less frequent than those of
      penetrating injuries, especially in the absence of significant musculoskeletal
      trauma. We present an unusual case of complete femoral artery and vein avulsion
      that resulted from a forced hip hyperextension and thigh abduction after slipping
      when a patient's foot became entrapped in a ladder. The patient presented with an
      acutely ischemic right lower extremity 8 hr postinjury, which necessitated
      immediate surgical exploration, temporary intravascular shunting, interposition
      grafting, and prophylactic fasciotomy. To our knowledge, this is the first such
      mechanism to be reported resulting in complete transection of both femoral artery
      and vein. We review the mechanism of injury and management.

PMID- 18619777
TI  - Outcomes of Amplatzer vascular plugs for occlusion of internal iliacs during
      aortoiliac aneurysm stent grafting.
AB  - We report on the outcomes of the Amplatzer vascular plug (AVP) for occlusion of
      the internal iliac artery (IIA) during stent grafting of aortoiliac and isolated
      common iliac artery aneurysms. We retrospectively reviewed 10 patients treated
      concomitantly with a single AVP in the IIA and endografting of the degenerative
      aneurysmal segment. Imaging review included pre- and postdeployment conventional
      angiography as well as pre- and postprocedure contrast-enhanced computed
      tomography (CT). Furthermore, subjective pre- and postprocedure exercise
      tolerance was also assessed, with specific attention directed toward the presence
      or absence of buttock claudication. Placement of the AVP precisely in the main
      trunk of the IIA was achieved in all cases using a standard up-and-over approach
      while maintaining patency of the distal trunk and both divisional IIA branches.
      No type II endoleaks through the AVP were identified intraoperatively or on
      follow-up CT imaging. Buttock claudication was absent in all but one patient,
      whose symptoms resolved at 6 weeks. The AVP device can be used as an alternative
      to coils to occlude the IIA at the time of stent graft repair of aortoiliac
      aneurysms. The deployment accuracy of this device allows for consistent
      preservation of the IIA divisional bifurcation and, thus, may allow for
      preservation of important pelvic collateral flow.

PMID- 18619778
TI  - The value of vein graft surveillance in bypasses performed with small-diameter
      vein grafts.
AB  - We assessed the impact of preoperative diameter of the venous conduit on
      reintervention rate and outcome following infrainguinal vein graft bypass.
      Consecutive infrainguinal vein bypasses between January 2001 and December 2006
      were reviewed. All patients underwent preoperative measurement of vein graft
      diameter (VGD). Grafts were classified into those with VGD <3.5 mm and those with
      VGD > or =3.5 mm. All patients were enrolled in a duplex surveillance program.
      The association between VGD and reintervention rate was assessed. Graft patency
      and amputation rates were compared. There were 377 bypasses followed up for a
      median of 23 months (range 8-67). VGD was <3.5 mm in 139 grafts (36.9%) and > or
      =3.5 mm in 238 grafts (63.1%). A higher proportion of smaller vein grafts (32.3%)
      required reintervention to maintain graft patency compared with larger conduits
      (20.2%) (chi(2) = 7.7, p < 0.001). VGD (odds ratio [OR] = 2.87, 95% confidence
      interval [CI] 1.63-3.81; p < 0.001), smoking (OR = 1.83, 95% CI 1.39-3.20; p =
      0.02), and type of bypass (OR = 1.86, 95% CI 1.49-2.47; p = 0.02) were variables
      associated with higher reintervention rate. There was no difference in graft
      patency (p = 0.13) or amputation rates (p = 0.35) between the two groups. Use of
      smaller vein grafts was associated with a higher reintervention rate. Provided
      that these grafts are surveyed and where necessary repaired, the use of smaller
      vein grafts is successful and expands the availability of autogenous conduit for
      infrainguinal arterial reconstruction.

PMID- 18619779
TI  - One patent intracranial collateral predicts tolerance of flow reversal during
      carotid angioplasty and stenting.
AB  - Internal carotid artery (ICA) flow reversal is an effective means of cerebral
      protection during carotid stenting. Its main limitation is that in the absence of
      adequate collateral flow it may not be tolerated by the patient. The purpose of
      this study was to determine if preoperative identification of intracranial
      collaterals with computerized tomographic (CTA) or magnetic resonance (MRA)
      angiography can predict adequate collateral flow and neurological tolerance of
      ICA flow reversal for embolic protection. This was a study of patients undergoing
      transcervical carotid angioplasty and stenting. Neuroprotection was established
      by ICA flow reversal. All patients underwent preoperative cervical and cerebral
      noninvasive angiography with CTA or MRA and had at least one patent intracranial
      collateral. Mean carotid artery back pressure was measured. Neurological changes
      during carotid clamping and flow reversal were continuously monitored with
      electroencephalography (EEG). Thirty-seven patients with at least one patent
      intracranial collateral on brain imaging with CTA or MRA were included. Mean
      carotid artery back pressure was 58 mm Hg. All procedures were technically
      successful. No EEG changes were present with common carotid artery occlusion and
      ICA flow reversal. One patent intracranial collateral provides sufficient
      cerebral perfusion to perform carotid occlusion and flow reversal with absence of
      EEG changes. Continued progress in noninvasive imaging modalities is becoming
      increasingly helpful in our understanding of cerebral physiology and selection of
      patients for invasive carotid procedures.

PMID- 18619781
TI  - Is Reinke's edema a precancerous lesion? Histological and electron microscopic
      aspects.
AB  - The objectives of this study were to evaluate morphologic alterations and
      precancerous lesions in Reinke's edema. Patients included were 54 smokers with
      bilateral Reinke's edema submitted to surgery in the Otolaryngology Department,
      Botucatu Medical School, Sao Paulo State University, Brazil, between 2002 and
      2006. All specimens were evaluated by light microscopy and five contralateral
      lesions were also evaluated by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). The main histological alterations were
      edema (100%), inflammation (81.48%), basal membrane (bm) thickening (77.77%), and
      vessel proliferation (75.92%). Epithelium alterations were classified as grade 0
      (11.11%), grade 1 (70.37%), grade 2 (14.81%), and grade 3 (3.70%). In the case
      included in grade 3 classification, microinvasive carcinoma was detected. SEM
      showed epithelial surface with some cellular desquamation, few microridges, and a
      polished and impermeable surface aspect. TEM showed epithelial hyperplasia, basal
      cells with different sizes, widening of the intercellular spaces, abnormal
      desmosome architecture, thickening of the bm, some electron-dense vesicles, and
      points of interruption. The morphological alterations presented in this study are
      not specific to Reinke's edema but this lesion can be the site of different
      grades of dysplasia and carcinoma, justifying the importance of periodic
      laryngeal endoscopic exams and meticulous histological analysis.

PMID- 18619780
TI  - Superiority of thoracoscopic sympathectomy over medical management for the
      palmoplantar subset of severe hyperhidrosis.
AB  - Severe hyperhidrosis is a disabling disorder whose management is controversial.
      Medical treatment consists of topical aluminum chloride, oral anticholinergics,
      ionotophoresis, and botulinum toxin A (Botox) injections. Despite the minimally
      invasive nature of thoracoscopic sympathectomy, there is a common perception that
      surgery is only a "last resort." The palmoplantar subtype of hyperhidrosis is
      particularly problematic for patients professionally and socially. The purpose of
      our study was to determine the safety, efficacy, and side effects of the various
      medical treatments vs. bilateral thoracoscopic sympathectomy (BTS) for
      palmoplantar hyperhidrosis. Consecutive patients (n = 192) were selected based on
      massive palmar sweating, similar level of plantar sweating, bimodal onset in
      early childhood or puberty, and exacerbation with ordinary hand lotion. A
      prospective cohort of 47 patients underwent medical treatment with their
      responses monitored on a prospective basis, and 145 patients underwent
      retrospective evaluation of their medical treatment based on their histories.
      Patients whose medical treatments failed or resulted in intolerable side effects
      were offered outpatient BTS surgery at the T2-T3 level. Of the 47 prospective
      patients, 46 received topical aluminum chloride, 40 anticholinergics, six
      iontophoresis, and 45 BTS surgery. Only one patient was successfully treated with
      aluminum chloride (2.2%) and one successfully treated with anticholinergics
      (2.5%), and these did not undergo surgery. Iontophoresis was not successful in
      any prospectively followed patient. BTS was effective in curing palmar
      hyperhidrosis in 100% of patients. The superiority of BTS vs. topical aluminum
      chloride, anticholinergics, and iontophoresis to successfully treat palmar
      hyperhidrosis was highly statistically significant (p < 0.001). For the
      retrospective group of 145 patients, 89 had been treated with topical aluminum
      chloride, 38 with oral anticholinergics, 31 with iontophoresis, eight with Botox,
      one with no medical treatment, and 144 with BTS surgery. All medical treatments
      failed with the exception that one patient was satisfied with anticholinergic
      treatment (2.6%), and this patient did not undergo BTS. BTS was successful in
      curing bilateral palmar hyperhidrosis in 99.3% (one unilateral failure due to
      adhesions). BTS was superior in treating palmar hyperhidrosis compared to
      aluminum chloride, anticholinergics, iontophoresis, and Botox (p < 0.001). The
      medically treated patients suffered significant side effects ranging from local
      stinging, cracking, and blistering to xerostomia, xerophthalmia, and blunted
      mentation. Overall, compensatory hyperhidrosis (CH) was present in 56% of
      patients undergoing BTS, but only 3.2% of BTS patients had severe CH with
      significant discomfort; all were men. There were no other significant operative
      complications. The safety and overwhelming efficacy of BTS compared to medical
      management of severe palmoplantar hyperhidrosis is demonstrated. Rather than
      being a "last resort," BTS can be confidently recommended as first-line treatment
      for the typical, severe form of palmoplantar hyperhidrosis.

PMID- 18619782
TI  - Transventricular chondroplastic laryngotomy--a new surgical technique for the
      endolarynx.
AB  - Current surgical techniques for laryngeal exposure pose distinct limitations. To
      address these issues, this article describes a novel surgical technique. Our
      technique, termed Transventricular Chondroplastic Laryngotomy, allows for
      extensive and direct external access to the endolarynx. This procedure is
      described in both a cadaver and animal models. Three pigs were submitted to
      thyroid cartilage window opening without touching the laryngeal ventricle, and
      seven animals were submitted to the full procedure, opening a thyroid cartilage
      window with wide ventricular opening. The animals were sacrificed 20 days
      following the procedure. Prior to sacrifice, all animals underwent laryngoscopic
      examination and following euthanasia, the larynx and cervical regions were
      examined grossly, in addition to histologically. This surgery allowed for
      extensive exposure of the ipsilateral vocal fold and the contralateral
      hemilarynx, through the laryngeal ventricle, and thus enabled bi-instrumental
      handling of the vestibular fold, laryngeal ventricle, and from the anterior
      commissure to the arytenoids, bilaterally. No postoperative complications were
      observed. Access to the ventricle was easily and directly achieved through the
      thyroarytenoid muscle. We hypothesize that transventricular chondroplastic
      laryngotomy will emerge as the surgical technique of choice in patients
      presenting with difficult exposure and/or traditional surgical instruments are
      not feasible. Future transventricular chondroplastic laryngotomy clinical
      applications of the procedure are discussed including the resection of lesions
      and more complex reconstruction of vocal folds.

PMID- 18619783
TI  - Long-term average spectrum in screening of voice quality in speech: untrained
      male university students.
AB  - Voice quality has mainly been studied in trained speakers, singers, and dysphonic
      patients. Few studies have concerned ordinary untrained university students'
      voices. In light of earlier studies of professional voice users, it was
      hypothesized that good, poor, and intermediate voices would be distinguishable on
      the basis of long-term average spectrum characteristics. In the present study,
      voice quality of 50 Finnish vocally untrained male university students was
      studied perceptually and using long-term average spectrum analysis of text
      reading samples of one minute duration. Equivalent sound level (Leq) of text
      reading was also measured. According to the results, the good and ordinary voices
      differed from the poor ones in their relatively higher sound level in the
      frequency range of 1-3 kHz and a prominent peak at 3-4 kHz. Good voices, however,
      did not differ from the ordinary voices in terms of the characteristics of the
      long-term average spectrum (LTAS). The strength of the peak at 3-4 kHz and the
      voice-quality scores correlated weakly but significantly. Voice quality and alpha
      ratio (level difference above and below 1 kHz) correlated likewise. Leq was
      significantly higher in the students with good and ordinary voices than in those
      with poor voices. The connections between Leq, voice quality, and the formation
      of the peak at 3-4 kHz warrant further studies.

PMID- 18619784
TI  - Comparing health locus of control in patients with Spasmodic Dysphonia,
      Functional Dysphonia and Nonlaryngeal Dystonia.
AB  - Locus of Control (LoC) refers to an individuals' perception of whether they are
      in control of life events. Health Locus of Control refers to whether someone
      feels they have influence over their health. Health Locus of Control has not been
      studied in any depth in voice-disordered patients. The objective of this study
      was to examine Health Locus of Control in three patient groups: (1) Spasmodic
      Dysphonia, (2) Functional Dysphonia and (3) a nondysphonic group with
      Nonlaryngeal Dystonia. LoC was measured and compared in a total of 57 patients
      using the Multidimensional Health Locus of Control Scales (diagnostic specific)
      Form C. Internal, Chance, and Powerful others LoC were measured and comparisons
      were made using one-way analysis of variance. Contrary to expectations Internal
      LoC was found to be significantly higher in the Functional Dysphonia group when
      compared to the other two groups. There was no significant difference between the
      groups in Chance or Powerful others LoC. The two organic groups, Spasmodic
      Dysphonia and Nonlaryngeal Dystonia, were more alike in Internal Health Locus of
      Control than the Functional Dysphonia group. The diagnostic nature of the groups
      was reflected in their LoC scores rather than their voice loss. These results
      contribute to the debate about the etiology of Spasmodic Dysphonia and will be of
      interest to those involved in the psychology of voice and those managing voice
      disordered patients.

PMID- 18619785
TI  - Bilateral occult mucosal bridges of the true vocal folds.
AB  - A mucosal bridge of the true vocal fold is a rare, benign anatomical finding that
      can cause dysphonia. It has been described by some in the literature as "occult"
      as it is often not visibly evident on flexible nasopharyngolaryngoscopy or
      strobovideolaryngoscopy, but mistakenly diagnosed as a sulcus vocalis (Sataloff
      RT, Rosen C, Hawkshaw M. Occult mucosal bridge of the vocal fold. Ear Nose Throat
      J. 1997; 76(12):850).(2) Final diagnosis is usually not made until microscopic
      direct laryngoscopy is performed and palpation of the true vocal fold reveals the
      mucosal bridge (Tanaka S, Hirano M, Umeno H, Tanaka Y. Mucosal bridge of the
      vocal fold [Japanese].(4)Nippon Jibiinkoka Gakkai Kaiho. 1991; 94(12):1853-1856).
      We describe a case of a 15-year-old boy complaining of long-standing hoarseness
      and found to have bilateral mucosal bridges of the true vocal folds. Previous
      reports cite cases of a unilateral mucosal bridge. We believe this is the first
      reported case of bilateral mucosal bridges.

PMID- 18619786
TI  - Plasmacytoma of larynx--a case report.
AB  - Plasma cell myeloma, the most common plasma cell neoplasm, is characterized by
      the presence of multiple lesions in the bone marrow. A single isolated lesion may
      occur either in bone (solitary plasmacytoma of bone) or in soft tissue
      (extramedullary plasmacytoma). Most cases of extramedullary plasmacytoma occur in
      the head and neck region. The diagnosis is established by histopathology and
      immunohistochemistry. A detailed evaluation for lesions at other sites is
      recommended as extramedullary plasmacytoma treated by radiation therapy has
      better survival rates than plasma cell myeloma, which is treated by chemotherapy.
      A case of plasmacytoma of the larynx is presented highlighting clinical and
      histological features with a review of literature.

PMID- 18619787
TI  - Computer-aided optimal designs for improving neural network generalization.
AB  - In this article we propose a new insight into the field of feed-forward neural
      network modeling. We considered the framework of the nonlinear regression models
      to construct computer-aided D-optimal designs for this class of neural models.
      These designs can be seen as a particular case of active learning. Classical
      algorithms are used to construct local approximate and local exact D-optimal
      designs. We observed that the so-called generalization of a neural network (the
      equivalent term, "predictive ability", is more familiar to statisticians) is
      improved when the D-efficiency of the chosen "learning set design" increases. We
      thus showed that the D-efficiency criterion can be the basis for a better
      strategy for the neural network learning phase than the standard uniform random
      strategy encountered in this field. Our proposition is based on two possible
      strategies: a One-Step Strategy or a Full Sequential Strategy. Intensive Monte
      Carlo simulations with an academic example show that the D-optimal "learning set
      design" strategies proposed lead to a substantial improvement in the use of
      neural network models.

PMID- 18619788
TI  - Computerized adaptive test for patients with knee impairments produced valid and
      responsive measures of function.
AB  - OBJECTIVE: Assess practicality of using a computerized adaptive test (CAT) in
      routine clinical practice, perform a psychometric evaluation of content range
      coverage and test precision, and assess known group construct validity,
      sensitivity to change and responsiveness of knee CAT functional status (FS)
      measures. STUDY DESIGN AND SETTING: Secondary analysis of retrospective intake
      and discharge rehabilitation FS data collected in a prospective cohort study.
      Data represented a convenience sample of 21,896 patients with knee impairments
      receiving outpatient physical therapy in 291 clinics in 30 U.S. states (2005
      2007). RESULTS: The CAT used an average of seven items to produce precise
      estimates of FS that adequately covered the content range with negligible floor
      and ceiling effects. Test information functions and standard errors supported FS
      measure precision. FS measures discriminated patients by age, symptom acuity,
      surgical history, condition complexity, and prior exercise history in clinically
      logical ways. Seventy-two percent of patients obtained discharge FS measures > or
      = minimal detectable change (95% confidence interval). Change of 9 FS units (0
      100 scale) represented minimal clinically important improvement, which 67% of
      patients obtained. CONCLUSION: The knee CAT was efficient and produced precise,
      valid, and responsive measures of FS for patients receiving therapy for knee
      impairments and functioned well in routine clinical application.

PMID- 18619789
TI  - Assessing continuity of care in a community diabetes program: initial
      questionnaire development and validation.
AB  - OBJECTIVE: To develop and validate a questionnaire based on agency theory to
      measure continuity of care in a community-based diabetes control program in
      Shanghai, China. STUDY DESIGN AND SETTING: Continuity of care was conceptualized
      in relation to two domains: information transfer and goal alignment. The
      questionnaire combined scales adopted from two validated questionnaires: the
      Primary Care Assessment Survey and the Summary of Diabetes Self-care Activities
      Measure. Patient interviews were conducted with 156 diabetes patients in the
      intervention group and 182 in the control group in two community health settings
      in Shanghai, China. The questionnaire was validated in terms of Likert-scaling
      assumptions, data completeness, score distribution, construct validity, and
      sensitivity. RESULTS: All scales consistently showed strong measurement
      properties in item reliability and validity. Requirements of data completeness
      and distribution were achieved in all scales. Principal components analysis of
      six scales provided a satisfactory explanation of the hypothesized scale-domain
      construction. CONCLUSIONS: The validation results suggested that the scales in
      our continuity of care questionnaire are consistent with the concept of
      continuity of care based on agency theory.

PMID- 18619790
TI  - The Singaporean English and Chinese versions of the EQ-5D achieved measurement
      equivalence in cancer patients.
AB  - OBJECTIVE: To assess measurement equivalence of the Singaporean English and
      Chinese versions of the EuroQol Group's 5-domain questionnaire (EQ-5D) in cancer
      patients. STUDY DESIGN AND SETTING: Seven hundred and seventy-one ethnic Chinese
      patients in Singapore were recruited, and they answered either an English or a
      Chinese version of the EQ-5D. Seven days later, a similar questionnaire in the
      same language was mailed to the patients. Regression analysis was used to assess
      equivalence of the mean values obtained by using the two language versions. The
      validity, responsiveness to change, and reliability of the two versions of the EQ
      5D were assessed and compared. RESULTS: Based on the prespecified equivalence
      margin of +/-10% for binary outcome, +/-0.05 for utility index, and +/-5 points
      in the visual analog scale, the two language versions of the EQ-5D gave
      equivalent mean values at item and scale levels. They also showed similar
      characteristics in validity, responsiveness, and reliability. For example, the
      test-retest reliability values for the EQ-5D utility index in the two language
      samples were identical in two significant digits: 0.79. CONCLUSION: The
      Singaporean English and Chinese versions of the EQ-5D were validated in cancer
      patients and were shown to achieve measurement equivalence.

PMID- 18619791
TI  - Interpretation and precision of the Observer Scar Assessment Scale improved by a
      revised scoring.
AB  - OBJECTIVE: To apply Rasch measurement to develop a rule for clinical
      interpretation of the Observer Scar Assessment Scale (OSAS) to help surgeons
      judge reported sum scores clinically. STUDY DESIGN AND SETTING: We used cross
      sectional data of a multicenter randomized clinical trial for the treatment of
      nontuberculous cervicofacial lymphadenitis in children. Rasch analysis was used
      on the OSAS scores obtained from scar photographs of 100 children after surgical
      or antibiotic treatment. RESULTS: Rasch analysis showed that all OSAS item rating
      scales needed revision and weighting. After doing so, raw scale scores could be
      converted into quantitative interval scale-based measures of scar quality. The
      clinical interpretation of the OSAS was clearly improved by the revised scoring.
      By using the Rasch-modeled item and person measures, the most likely OSAS score
      patterns associated with the revised OSAS sum scores could be determined.
      CONCLUSIONS: The Rasch analysis improved the measurement properties and clinical
      interpretability of the OSAS instrument.

PMID- 18619792
TI  - A philosophical perspective supports the need for patient-outcome studies in
      diagnostic test evaluation.
AB  - OBJECTIVE: Most clinical research evaluates diagnostic tests by accuracy measures
      such as sensitivity and specificity. This is stimulated by the Standards for
      Reporting of Diagnostic Accuracy initiative, which focuses on accuracy in the
      widely accepted guidelines. Referring to the clinical consequences of diagnostic
      tests, many epidemiologists recognize the importance of patient outcome studies
      in addition to accuracy studies. However, there is a theoretical argument that
      stipulates the need for patient outcome studies, which has thus far been
      overlooked. RESULTS: Using a philosophical argument, we show that the definition
      of disease necessarily involves the concept of function, which in turn is
      inextricably related to outcome. Consequently, diagnostic tests that establish
      the presence or absence of disease cannot be evaluated without measuring patient
      outcome. Patient outcome studies are therefore the definitive means to assess the
      merits of a diagnostic test. CONCLUSION: The need for patient outcome studies is
      not due to pragmatic reasons, as previous authors argued, but is based on a
      philosophical argument relating the definition of disease to the concept of
      function. We propose that authors justify the use of accuracy studies in papers
      reporting diagnostic test evaluation by describing the association between gold
      standard test and patient outcome.

PMID- 18619793
TI  - Registered post achieved a higher response rate than normal mail--a randomized
      controlled trial.
AB  - OBJECTIVE: The aim was to study the most effective method for increasing response
      rates to postal questionnaires by comparing normal post with registered mail and
      to assess the cost implications of the two mailing methods. STUDY DESIGN AND
      SETTING: General Practitioners in Victoria (n=1,550) were randomized to receive a
      research questionnaire via either normal post or registered mail. RESULTS: The
      overall response rate for the study after two reminders was 76.1% (1,179/1,550).
      After the initial mail out the response rate for the registered mail arm was
      55.9% (n=433) compared to the normal post arm, 40.1% (n=311, P-value <0.001).
      After the first and second reminders the response rates dropped, registered mail
      obtained a response rate of 47.4% (n=162) and 37.8% (n=68), respectively,
      compared to a response rate of 28.0% (n=130) and 22.5% (n=75) for normal post.
      Overall, the cumulative response rate for the registered mail was greater, 85.6%
      (n=663) compared to 66.6% (n=516) for the normal post arm (P-value <0.001) There
      was a total cost difference between the registered and normal method of AUD
      $1,531.50. CONCLUSION: Registered post when used for mail out of the initial
      questionnaire and all subsequent reminders is a more effective yet more expensive
      method for achieving a high response rate.

PMID- 18619794
TI  - Scales could be developed based on simple clinical ratings of International
      Classification of Functioning, Disability and Health Core Set categories.
AB  - OBJECTIVE: The aim of the study was to examine whether clinical ratings of
      International Classification of Functioning, Disability and Health categories can
      be integrated into parametric scales, which provide a reliable estimation of
      specified patient problems and rehabilitation goals using the example of mobility
      of the upper and lower extremities in the acute hospital situation. STUDY DESIGN
      AND SETTING: Psychometrical study based on data from a prospective multicentric
      cohort study in patients with musculoskeletal conditions in the acute hospital.
      RESULTS: Two hundred thirty-four patients were included (mean age 56, 50% female.
      Forty-four percent with a diagnosis involving lower extremities, 18% with a
      diagnosis involving the hip, 18% with a diagnosis involving upper extremities,
      16% with a diagnosis involving the spine). After adjustment for differential item
      functioning two separate scales for upper and lower extremity mobility could be
      constructed. The constructed scales had 10 (upper) and eight (lower) items
      displaying adequate to good fit. CONCLUSION: The results of this study indicate
      that it could be possible to develop scales based on categories of the
      International Classification of Functioning, Disability and Health Core Sets.
      This may be a promising approach for areas where psychometrically sound measures
      are not available.

PMID- 18619795
TI  - Exposure to environmental tobacco smoke in Chinese new mothers decreased during
      pregnancy.
AB  - OBJECTIVE: To determine the current status of environmental tobacco smoke (ETS)
      exposure in new mothers living in urban Shanghai. STUDY DESIGN AND SETTING: A
      cross-sectional study was carried out in three communities of Shanghai from June
      2005 to August 2006. A total of 950 new mothers with infants aged 5-8 months were
      recruited in community health centers by trained health workers. The prevalence
      of ETS exposure was determined for before, during, and after pregnancy. Chi
      square test and logistical regression analysis were used in statistical analysis.
      RESULTS: The prevalence of ETS exposure was 55.9% (95% confidence interval [CI]:
      52.2, 59.6) before pregnancy and decreased significantly to 41.9% (95% CI: 38.2,
      45.6) during pregnancy. However, the amount and time of exposure to ETS changed
      little before, during, and after pregnancy for those exposed. Among husbands who
      ever smoked, 14.4% stopped smoking before pregnancy, 38.1% changed smoking
      behaviors during pregnancy, and after pregnancy 10.7% quit smoking, whereas three
      nonsmoking husbands began to smoke. CONCLUSION: Pregnancy is a very important
      time period to implement tobacco control projects targeting young male smokers.

PMID- 18619796
TI  - Factors distinguishing general practitioners who more readily participated in a
      large randomized trial were identified.
AB  - OBJECTIVE: To investigate factors associated with the successful recruitment of
      general practices to a randomized controlled trial. STUDY DESIGN AND SETTING:
      Analysis of accrual of primary care centers to a randomized controlled trial in
      the UK. RESULTS: Those practices promptly agreeing to take part had better target
      achievement and a higher proportion of white British residents locally.
      Participating practices had a mean Quality and Outcomes Framework attainment of
      92% of the points available, whereas nonparticipating practices achieved 88%
      (P=0.009). Participating practices were located in areas with a higher proportion
      of white British residents (mean 89%), in comparison to nonparticipating
      practices (mean 84%, P=0.004). Reasons given by practices to explain
      nonparticipation were primarily related to internal factors, with 38% of
      practices approached saying that they could not participate for such reasons.
      CONCLUSION: There are some small differences between participating practices and
      nonparticipants in achievement of government targets and in the local ethnic mix.
      The primary reason given by practices for nonparticipation was workload or time
      pressures, with over a third of practices reporting being prevented by issues
      relating to practice organization. It may be that practices with workload or
      organizational difficulties require additional support to participate in
      research.

PMID- 18619797
TI  - Quantitative assessment of unobserved confounding is mandatory in nonrandomized
      intervention studies.
AB  - OBJECTIVE: In nonrandomized intervention studies unequal distribution of patient
      characteristics in the groups under study may hinder comparability of prognosis
      and therefore lead to confounding bias. Our objective was to review methods to
      control for observed confounding, as well as unobserved confounding STUDY DESIGN
      AND SETTING: We reviewed epidemiologic literature on methods to control for
      observed and unobserved confounding. RESULTS: Various methods are available to
      control for observed (i.e., measured) confounders, either in the design of data
      collection (i.e., matching, restriction), or in data analysis (i.e., multivariate
      analysis, propensity score analysis). Methods to quantify unobserved confounding
      can be categorized in methods with and without prior knowledge of the effect
      estimate. Without prior knowledge of the effect estimate, unobserved confounding
      can be quantified using different types of sensitivity analysis. When prior
      knowledge is available, the size of unobserved confounding can be estimated
      directly by comparison with prior knowledge. CONCLUSION: Unobserved confounding
      should be addressed in a quantitative way to value the inferences of
      nonrandomized intervention studies.

PMID- 18619798
TI  - Socioeconomic factors influence selection and participation in a population-based
      case-control study of head and neck cancer in Scotland.
AB  - OBJECTIVE: We aimed to investigate the association between socioeconomic factors
      and selection and participation biases in a population-based case-control study
      of head and neck cancer conducted in the city of Glasgow, UK. METHODS: General
      Practices (GP) of the case subjects were the sampling frame from which age and
      sex-matched controls were randomly selected. Participant and nonparticipant
      postcodes of cases and controls were linked to the area-based Scottish Index of
      Multiple Deprivation. Comparisons of study selection and participation were made
      with the Glasgow study-base population. RESULTS: Cases were from significantly
      more deprived areas than controls. Overall, participation was low for both cases
      (34.9%) and controls (34.7%). Our overall control sample was not similar to the
      general population of Glasgow having "over selected" from deprived areas.
      Individuals from more affluent areas were more likely to participate providing a
      set of interviewed participants reflecting the socioeconomic distribution of
      Glasgow. CONCLUSIONS: Low participation rates in case-control studies remain a
      problem and socioeconomic factors strongly affect participation. A control sample
      selection biased in one direction was offset by participation bias in the
      opposite direction -- fortuitously providing a representative control sample.
      Selecting controls from case GP lists needs to be implemented with care with
      attention paid to obtaining evidence on the underlying socioeconomic
      characteristics of GP populations, especially for diseases with a skewed
      socioeconomic distribution.

PMID- 18619799
TI  - Randomized patients in IBS research had different disease characteristics
      compared to eligible and recruited patients.
AB  - OBJECTIVE: The recruitment process may generate a selected patient sample, which
      may threaten the generalizability of trial results. This risk is particularly
      high in case disease and patient characteristics demonstrate a wide variation,
      such as in irritable bowel syndrome (IBS). We compared IBS patients who were
      selected, approached, and randomized to participate in a clinical trial assessing
      the efficacy of dietary fiber therapy in IBS. STUDY DESIGN AND SETTING:
      Retrospective survey in primary care patients diagnosed with IBS by their general
      practitioner in the past 2 years selected and invited for participation in a
      trial. Characteristics were compared between randomized patients (n=193)
      nonrandomized eligible patients (n=371), and patients not eligible for
      participating in the trial (n=724). RESULTS: Of the 2,100 IBS patients, 1,288
      (61%) returned the questionnaire. Randomized patients had a higher intensity of
      IBS abdominal pain as compared to the other groups, a higher consultation rate
      and a longer IBS disease history. Noneligible patients had less active IBS
      symptoms. CONCLUSIONS: Patients randomized do differ from those nonrandomized in
      IBS disease characteristics. These observations may have implications for the
      applicability of our research outcome.

PMID- 18619800
TI  - Using multiple data features improved the validity of osteoporosis case
      ascertainment from administrative databases.
AB  - OBJECTIVES: The aim was to construct and validate algorithms for osteoporosis
      case ascertainment from administrative databases and to estimate the population
      prevalence of osteoporosis for these algorithms. STUDY DESIGN AND SETTING:
      Artificial neural networks, classification trees, and logistic regression were
      applied to hospital, physician, and pharmacy data from Manitoba, Canada.
      Discriminative performance and calibration (i.e., error) were compared for
      algorithms defined from different sets of diagnosis, prescription drug,
      comorbidity, and demographic variables. Algorithms were validated against a
      regional bone mineral density testing program. RESULTS: Discriminative
      performance and calibration were poorer and sensitivity was generally lower for
      algorithms based on diagnosis codes alone than for algorithms based on an
      expanded set of data features that included osteoporosis prescriptions and age.
      Validation measures were similar for neural networks and classification trees,
      but prevalence estimates were lower for the former model. CONCLUSION: Multiple
      features of administrative data generally resulted in improved sensitivity of
      osteoporosis case-detection algorithm without loss of specificity. However,
      prevalence estimates using an expanded set of features were still slightly lower
      than estimates from a population-based study with primary data collection. The
      classification methods developed in this study can be extended to other chronic
      diseases for which there may be multiple markers in administrative data.

PMID- 18619801
TI  - R and S-PLUS produced different classification trees for predicting patient
      mortality.
AB  - OBJECTIVE: There is a growing interest in using classification and regression
      trees in biomedical research. R and S-PLUS are two statistical programming
      languages that share a similar syntax and functionality. Both R and S-PLUS allow
      users to fit classification and regression trees. The objective was to compare
      classification trees grown using R with those grown using S-PLUS. STUDY DESIGN
      AND SETTING: Using data on 9,484 patients hospitalized with an acute myocardial
      infarction, we compared the classification trees for predicting mortality that
      were grown using R and S-PLUS. We also used repeated split-sample derivation to
      determine the predictive accuracy of classification trees grown using R and S
      PLUS. RESULTS: The classification tree grown using R was substantially more
      parsimonious than the one grown using S-PLUS. The pruned classification tree
      grown using R was equal to a classification tree that was obtained by removing
      six subtrees from the pruned classification tree grown using S-PLUS. Repeated
      split-sample validation was then used to demonstrate that classification trees
      constructed using S-PLUS had greater discrimination and accuracy compared to
      classification trees grown using R. CONCLUSIONS: R can produce different
      classification trees than S-PLUS using the same data.

PMID- 18619802
TI  - Diagnostic properties of a symptoms scale for diagnosing reflux esophagitis.
AB  - OBJECTIVE: To the objective of the study was to determine accuracy and predictive
      values of a symptoms scale for diagnosing reflux esophagitis (RE). STUDY DESIGN
      AND SETTING: Standard criterion study. All recruited patients from two centers in
      Chile underwent both digestive endoscopy (reference standard) and a symptoms
      scale known to be valid and reliable for diagnosing gastroesophageal reflux
      disease. The RE variable was dealt with dichotomously. A receiver operating
      characteristic curve was constructed. Sensitivity, specificity, positive and
      negative predictive values, and positive and negative likelihood ratios of the
      scale were calculated. RESULTS: Two hundred and thirty eight (238) subjects
      (57.6% female), with an average age of 44.2+/-13.0 years were included. Of these,
      57.1% presented with RE. With a cut-off score of six, association was confirmed
      between the symptoms scale and RE with an odds ratio of 7.26 and a correct
      classification i.e. diagnostic accuracy of 73.1%. Sensitivity, specificity,
      positive and negative predictive values, positive and negative likelihood ratios,
      of 74.3%, 71.6%, 77.7%, 67.6%, 2.61, and 0.36 respectively, were obtained.
      CONCLUSION: A seven-item symptoms scale when compared to endoscopy as gold
      standard was useful for diagnosing RE. Using a cutoff of six points, the
      diagnostic accuracy of the scale was 73.1%.

PMID- 18619803
TI  - An easy mathematical proof showed that time-dependent bias inevitably leads to
      biased effect estimation.
AB  - OBJECTIVE: Time-dependent bias occurs when future exposure status is analyzed as
      being known with start of observation. As this bias is common, we sought to
      determine whether it always leads to biased effect estimation. We also sought to
      determine the direction of the effect bias. STUDY DESIGN AND SETTING: We derived
      an easy mathematical proof investigating the nature of time-dependent bias. We
      applied the general mathematical result to data from a prospective cohort study
      on the incidence of hospital infection in intensive care: Here, we investigated
      the effect of time-dependent hospital infection status on intensive care unit
      stay. The nature of time-dependent bias was also illustrated graphically.
      RESULTS: Biased effect estimation is a mathematically inevitable consequence of
      time-dependent bias, because the number of individuals at risk of exposure is
      distorted over the course of time. In case of a time-dependent exposure that
      prolongs time until the study endpoint, the prolonging effect will be
      overestimated. CONCLUSION: Because time-dependent bias inevitably leads to
      erroneous findings, it is a major concern that it is common in the clinical
      literature. Time-dependent bias can be avoided by proper hazard-based analyses.

PMID- 18619804
TI  - Specific HRQL instruments and symptom scores were more responsive than preference
      based generic instruments in patients with GERD.
AB  - OBJECTIVE: To determine relative responsiveness of disease-specific and generic
      preference-based health-related quality of life instruments in gastroesophageal
      reflux disease (GERD). STUDY DESIGN AND SETTING: We compared standardized
      response means (SRM) of disease-specific and preference-based instruments in 217
      outpatients with GERD. RESULTS: Quality of Life in Reflux and Dyspepsia and
      symptom scores were responsive across all domains, whereas global rating of
      change and Work Productivity and Activity Impairment-GERD only in single domains.
      The most responsive were Quality of Life in Reflux and Dyspepsia food/drink
      problems (SRM: 1.90, 95% confidence interval [CI]: 1.76-2.03) and vitality (SRM:
      1.68, 95% CI 1.55-1.82) domains, Work Productivity and Activity Impairment-GERD
      workdays with reflux symptoms (SRM: 2.02, 95% CI 1.84-2.19), symptoms of
      heartburn (SRM: 1.83, 95% CI 1.69-1.96) and acid reflux (SRM: 1.48, 95% CI 1.35
      1.62), and global rating of change in stomach problems (SRM: 2.19, 95% CI 2.05
      2.32). The least responsive were Work Productivity and Activity Impairment-GERD
      domains related to hours absent at work (SRM: 0.22, 95% CI 0.05-0.38), reduced
      productivity at work (SRM: 0.66, 95% CI 0.48-0.83) and during other activities
      (SRM: 0.78, 95% CI 0.65-0.92), as well as emotional global rating of change (SRM:
      0.72, 95% CI 0.58-0.85), and the standard gamble (SRM: 0.35, 95% CI 0.21-0.48),
      which was less responsive than the feeling thermometer (SRM: 0.92, 95% CI 0.78
      1.05). CONCLUSIONS: In patients with GERD, disease-specific health-related
      quality of life instruments and symptom scores showed greater responsiveness than
      preference-based generic instruments. The feeling thermometer proved more
      responsive than the standard gamble.

PMID- 18619805
TI  - The Charlson comorbidity index is adapted to predict costs of chronic disease in
      primary care patients.
AB  - OBJECTIVE: (1) To determine chronic illness costs for large cohort of primary
      care patients, (2) to develop prospective model predicting total costs over one
      year, using demographic and clinical information including widely used
      comorbidity index. STUDY DESIGN AND SETTING: Data including diagnostic,
      medication, and resource utilization were obtained for 5,861 patients from
      practice-based computer system over a 1-year period beginning December 1, 1993,
      for retrospective analysis. Hospital cost data were obtained from hospital cost
      accounting system. RESULTS: Average annual per patient cost was $2,655. Older
      patients and those with Medicare or Medicaid had higher costs. Hospital costs
      were $1,558, accounting for 58.7% of total costs. In the predictive model,
      individuals with higher comorbidity incurred exponentially higher annual costs,
      from $4,317 with comorbidity score of two, to $5,986 with score of three, to
      $13,326 with scores greater than seven. To use an adapted comorbidity index to
      predict total yearly costs, four conditions should be added to the index:
      hypertension, depression, and use of warfarin with a weight of one, skin
      ulcers/cellulitis, a weight of two. CONCLUSION: The adapted comorbidity index can
      be used to predict resource utilization. Predictive models may help to identify
      targets for reducing high costs, by prospectively identifying those at high risk.

PMID- 18619806
TI  - Literacy affected ability to adequately discriminate among categories in
      multipoint Likert Scales.
AB  - OBJECTIVES: To assess the effect of inability to read on a five-point Likert
      scale, using the WHOQOL-BREF response scale. It is hypothesized that inability to
      read is related to loss of discriminant power among the five-category response
      scale. STUDY DESIGN AND SETTING: In a cross-sectional design, nonreaders (n=141)
      and subjects educated at a graduate level (n-907) were assessed. Statistical
      analyses combined classic and modern psychometric approaches (Confirmatory factor
      analysis and Rasch analysis). RESULTS: There is a remarkable difference in the
      psychometric performance of items across the two subgroups. Fit indexes proved to
      be closer to the ideal for the graduate group, but not for the nonreader group.
      Reducing the number of response categories improved the model exclusively for the
      nonreader sample. Nonreaders do not interpret the scale as a true five-category
      scale, but exhibit a response pattern indicative that only three categories are
      in fact considered. CONCLUSION: These results confirm the hypothesis that a
      multiple-category response scale is not suitable for nonreaders. They suggest
      that a simpler response scale should be adopted to achieve a more reliable and
      satisfactory psychometric performance in this population. This effect seems to be
      stronger when more abstract and subjective constructs are involved.

PMID- 18619807
TI  - Evaluation of a diabetes management program in China demonstrated association of
      improved continuity of care with clinical outcomes.
AB  - OBJECTIVE: The aim of the study was to evaluate a community-based diabetes
      management program in Shanghai, China and to examine the association between
      continuity of care and clinical outcomes. STUDY DESIGN AND SETTING: The diabetes
      management program was implemented in downtown Shanghai. One hundred fifty-six
      patients participated in the intervention group and 182 patients were in the
      control group. Participants were elders without severe diabetic complications.
      Patient weight, body mass index, blood pressures, and fasting blood glucose were
      collected from outpatient records at baseline and the end of the study in both
      groups. Fructosamine level was measured to monitor glycemic control for patients
      in the intervention group. Continuity of care was measured based on our broad
      definition. RESULTS: Improved patient health outcomes were observed in the
      diabetes management program: patients in the intervention group significantly
      reduced their weight, systolic blood pressure, and fasting blood glucose compared
      with those in the control group (P<0.05). In hierarchical regression models,
      continuity of care scales had a significant association with weight loss and
      fasting blood glucose reduction. CONCLUSION: This study suggested that continuity
      based on broad terms can act as an important management tool to improve the
      quality of primary care in similar urban settings.

PMID- 18619808
TI  - Modified WHODAS-II provides valid measure of global disability but filter items
      increased skewness.
AB  - OBJECTIVE: The WHODAS-II was substantially modified for use in the World Mental
      Health Surveys. This article considers psychometric properties and implications
      of filter items used to reduce respondent burden of the modified WHODAS-II. STUDY
      DESIGN AND SETTING: Seventeen surveys in 16 countries administered a modified
      WHODAS-II to population samples (N=38,934 adults). Modifications included
      introducing filter questions for four subscales and substituting questions on the
      number of days activity was limited for the Life Activities domain. We evaluated
      distributional properties, reliability, and validity of the modified WHODAS-II.
      RESULTS: Most respondents (77%-99%) had zero scores on filtered subscales. Lower
      bound estimates of internal consistency (alpha) for the filtered subscales were
      typically in the 0.70s, but were higher for the Global scale. Loadings of
      subscale scores on a Global Disability factor were moderate to high. Correlations
      with the Sheehan Disability Scale were modest but consistently positive, while
      correlations with SF-12 Physical Component Summary were considerably higher.
      Cross-national variability in disability scores was observed, but was not readily
      explainable. CONCLUSIONS: Internal consistency and validity of the modified
      WHODAS-II was generally supported, but use of filter questions impaired
      measurement properties. Group differences in modified WHODAS-II disability scores
      may be compared within, but not necessarily across, countries.

PMID- 18619809
TI  - Longitudinal and cross-sectional validity of the DynaPort Knee Test in adults
      with nontraumatic knee complaints in general practice.
AB  - OBJECTIVE: The aim of the study was to determine the cross-sectional and
      longitudinal validity of a performance-based assessment of knee function,
      DynaPort KneeTest (DPKT), in first-time consulters with nontraumatic knee
      complaints in general practice. METHODS: Patients consulting for nontraumatic
      knee pain in general practice aged >18 years were enrolled in the study. At
      baseline and 6-months follow-up knee function was assessed by questionnaires and
      the DPKT; a physical examination was also performed at baseline. Hypothesis
      testing assessed the cross-sectional and longitudinal validity of the DPKT.
      RESULTS: Eighty-seven patients were included for the DPKT, 86 were available for
      analysis. The studied population included 44 women (51.2%), the median age was 54
      (range 18-81) years. At follow up, 77 patients (89.5%) were available for the
      DPKT. Only 3 out of 11 (27%) predetermined hypotheses concerning the cross
      sectional and longitudinal validity were confirmed. Comparison of the general
      practice and secondary care population showed a major difference in baseline
      characteristics, DynaPort Knee Score, internal consistency, and hypotheses
      confirmation concerning the construct validity. CONCLUSION: The validity of the
      DPKT could not be demonstrated for first-time consulters with nontraumatic knee
      complaints in general practice. Measurement instruments developed and validated
      in secondary care are therefore not automatically also valid in primary care
      setting.

PMID- 18619810
TI  - Reducing population stratification bias: stratum matching is better than
      exposure.
AB  - OBJECTIVE: Genetic studies of complex human diseases rely heavily on the
      epidemiologic association paradigm, particularly the population-based case
      control designs. This study aims to compare the matching effectiveness in terms
      of bias reduction between exposure matching and stratum matching. STUDY DESIGN
      AND SETTING: Formulas for population stratification bias were derived. An index
      of matching effectiveness was constructed to compare the two types of matching.
      RESULTS: It was found that exposure matching can paradoxically increase the
      magnitude of population stratification bias sometimes, whereas stratum matching
      can guarantee to reduce it. CONCLUSION: The authors propose two simple rules for
      genetic association studies: (a) to match on anything that helps to delineate
      population strata such as race, ethnicity, nationality, ancestry, and birthplace
      and (b) to match on an exposure only when it is a strong predictor of the disease
      and is expected to have great variation in prevalence across population strata.

PMID- 18619811
TI  - Development of a complex intervention improved randomization and informed consent
      in a randomized controlled trial.
AB  - OBJECTIVE: Multicenter randomized trials are required for pragmatic evaluations
      of health care interventions, but recruitment is difficult. Systematic reviews
      failed to identify robust strategies to improve recruitment. We developed and
      evaluated a complex intervention to increase levels of randomization and informed
      consent. STUDY DESIGN AND SETTING: The ProtecT (Prostate testing for cancer and
      Treatment) trial compares radical surgery, radical conformal radiotherapy, and
      active monitoring for men aged 50-69 years with localized prostate cancer. The
      intervention was developed using qualitative research methods (content, thematic
      and conversation analysis). Rates of randomization and immediate acceptance of
      allocation were measured every 6 months to evaluate the impact of the
      intervention. RESULTS: The complex intervention comprised reviews of centers
      falling below study targets, training programmes, documents and individually
      tailored feedback. Over 65% of eligible participants consented to randomization.
      Trial participants became increasingly well informed as immediate acceptance of
      allocation rose from 65% to 81% between 2001 and 2005. CONCLUSION: This complex
      intervention resulted in high levels of randomization and informed consent in a
      difficult trial. The generic aspects of the intervention could be applied to
      other trials to maximize randomization and informed consent, and allow the
      mounting of trials previously considered too difficult.

PMID- 18619812
TI  - Published randomized controlled trials of drug therapy for dementia often lack
      complete data on harm.
AB  - OBJECTIVE: The objective of the study was to determine the extent to which
      published randomized controlled trials (RCTs) report data on harm. STUDY DESIGN
      AND SETTING: A systematic search strategy was used to identify RCTs published
      between 1996 and 2005 on the use of cholinesterase inhibitors or atypical
      antipsychotics in patients with dementia. A structured abstraction form was used
      to determine if data on mortality or serious adverse events were reported and if
      the articles followed Consolidated Standards of Reporting Trials format for
      reporting harm. RESULTS: Thirty-three RCTs were identified (27 on cholinesterase
      inhibitors and 6 on atypical antipsychotics). Nineteen trials (58%) had explicit
      data on mortality and only four (12%) reported regulatory-agency-defined serious
      adverse events. Most abstracts (31, 94%) stated that harm was studied but few
      studies (9, 27%) provided a clear definition of the measures of harm.
      CONCLUSIONS: Although most published RCTs state that they examine harm, many
      failed to provide data on mortality and most lacked clear definitions or detailed
      analyses of harm. Better reporting of harm would provide timely and important
      information that could help physicians and the public to make more informed
      decisions.

PMID- 18619813
TI  - Tolerability and safety of olive oil-based lipid emulsion in critically ill
      neonates: a blinded randomized trial.
AB  - OBJECTIVE: We assessed the safety and tolerability of an olive oil-based lipid
      emulsion compared with a soybean-based lipid emulsion in critically ill neonates.
      METHODS: A double-blinded, randomized study was conducted in critically ill
      neonates requiring parenteral nutrition in the first week of life. Infants were
      randomized to receive a lipid emulsion based on olive oil (OO; ClinOleic) or
      soybean oil (SO; Intralipid) for a minimum of 5 d. Plasma phospholipid fatty
      acids, F(2)-isoprostanes, liver function, and clinical outcome were assessed
      after 5 d of therapy. RESULTS: Seventy-eight neonates (men gestational age 37 wk,
      range 26-41 wk) received OO (n = 39) or SO (n = 39). Both emulsions were well
      tolerated with no adverse events observed. At day 5, plasma phospholipid oleic
      acid (C18:1omega-9) levels increased in infants receiving OO compared with lower
      levels in infants receiving SO (mean percentage +/- SD 33.1 +/- 6.4 for OO versus
      18.6 +/- 2.4 for SO; mean difference -14.7 mmol/L, 95% confidence interval -17.5
      to -11.9). The increase in plasma phospholipid linoleic acid levels was
      attenuated in infants receiving OO (mean percentage +/- SD 12.6 +/- 3.0 for OO
      versus 23.7 +/- 6.9 for SO; adjusted mean 11.4 mmol/L, 95% confidence interval
      8.1-14.8). No differences were observed in plasma F(2)-isoprostane levels
      according to the type of lipid emulsion received. CONCLUSION: The OO-based
      emulsion (ClinOleic) was well tolerated in critically ill neonates. Differences
      in plasma phospholipids at day 5 reflected the fatty acid composition of the
      administered emulsion. No significant differences in plasma F(2)-isoprostane
      levels were detected after 5 d of lipid administration.

PMID- 18619814
TI  - A tale of two nutritionists (or the importance of analysis plans).

PMID- 18619816
TI  - Anti-Toxoplasma gondii RH strain activity of herbal extracts used in traditional
      medicine.
AB  - Methanolic extracts of 15 traditional medicines used to treat Toxoplasma gondii
      were tested in vitro for their anti-T. gondii activity and cytotoxicity. The
      median effective concentration (EC(50)) values for the herbal extracts ranged
      from 0.11mg/mL to 2.28mg/mL. Significant anti-T. gondii RH strain activity was
      observed with Zingiber officinale extracts (EC(50)=0.18mg/mL), which displayed a
      highly selective toxicity (selectivity=10.1). Sophora flavescens Aiton extracts
      also showed high anti-T. gondii activity (EC(50)=0.20mg/mL) and a high selective
      toxicity (4.6). This indicates that Z. officinale and S. flavescens Aiton
      extracts may be sources of new anti-T. gondii compounds.

PMID- 18619815
TI  - Longitudinal progression of negative symptoms in schizophrenia: a new look at an
      old problem.
AB  - OBJECTIVE: Longitudinal analysis is crucial in determining the ability of new
      interventions to successfully reduce negative symptoms in schizophrenia. However,
      there are still conflicting reports as to whether there are significant treatment
      effects on these symptoms and the extent of these effects. We examine the
      possible effects of analysis method on these questions. METHODS: We use
      generalized linear mixed models (GLMM) to assess the change in specific negative
      symptom items following treatment changes in two separate cohorts of
      schizophrenia patients, one chronic and one first episode. RESULTS: Both data
      sets indicate that examining the change in prevalence of moderate to severe
      symptoms provides a useful estimate of the effect size associated with changes in
      treatment that often differs from that given using analysis of means.
      CONCLUSIONS: The use of categorical longitudinal methods may be critical to
      determining the responsiveness of negative symptoms to treatment as well as
      determining the stability of these symptoms over time.

PMID- 18619818
TI  - A bioinformatic approach to understanding antibiotic resistance in intracellular
      bacteria through whole genome analysis.
AB  - Intracellular bacteria survive within eukaryotic host cells and are difficult to
      kill with certain antibiotics. As a result, antibiotic resistance in
      intracellular bacteria is becoming commonplace in healthcare institutions. Owing
      to the lack of methods available for transforming these bacteria, we evaluated
      the mechanisms of resistance using molecular methods and in silico genome
      analysis. The objective of this review was to understand the molecular mechanisms
      of antibiotic resistance through in silico comparisons of the genomes of obligate
      and facultative intracellular bacteria. The available data on in vitro mutants
      reported for intracellular bacteria were also reviewed. These genomic data were
      analysed to find natural mutations in known target genes involved in antibiotic
      resistance and to look for the presence or absence of different resistance
      determinants. Our analysis revealed the presence of tetracycline resistance
      protein (Tet) in Bartonella quintana, Francisella tularensis and Brucella ovis;
      moreover, most of the Francisella strains possessed the blaA gene, AmpG protein
      and metallo-beta-lactamase family protein. The presence or absence of folP
      (dihydropteroate synthase) and folA (dihydrofolate reductase) genes in the genome
      could explain natural resistance to co-trimoxazole. Finally, multiple genes
      encoding different efflux pumps were studied. This in silico approach was an
      effective method for understanding the mechanisms of antibiotic resistance in
      intracellular bacteria. The whole genome sequence analysis will help to predict
      several important phenotypic characteristics, in particular resistance to
      different antibiotics. In the future, stable mutants should be obtained through
      transformation methods in order to demonstrate experimentally the determinants of
      resistance in intracellular bacteria.

PMID- 18619817
TI  - An immunomodulating dipeptide, SCV-07, is a potential therapeutic for recurrent
      genital herpes simplex virus type 2 (HSV-2).
AB  - Herpes simplex virus type 2 (HSV-2) infections produce a recurrent disease state
      associated with susceptibility to other pathogens, including human
      immunodeficiency virus (HIV), and cannot be cured by current therapeutic
      treatments. The HSV-2 epidemic must therefore be addressed by therapeutic
      strategies that reduce recurrent lesions and ideally lack the possibility for
      development of drug resistance. To this end, the therapeutic potential of SCV-07
      (gamma-D-glutamyl-L-tryptophan), a synthetic dipeptide with potent
      immunomodulatory and antimicrobial activity, was studied in the guinea pig model
      of recurrent genital HSV-2. Initial evaluations showed that when delivered
      orally, but not subcutaneously, SCV-07 significantly reduced recurrent lesions.
      Oral dose ranging studies indicated that, of the tested amounts, 5microg/kg was
      optimal when delivered after an overnight fast. Interestingly, fasting induced a
      significant increase in recurrent lesions in vehicle-treated guinea pigs relative
      to non-fasted animals. Despite this increase, SCV-07 significantly reduced lesion
      formation in treated animals but showed no durability following cessation of
      treatment. In fact, this regimen of SCV-07 treatment produced statistically
      indistinguishable outcomes compared with those provided by topical aciclovir.
      These data illustrate that SCV-07 may provide an easily administered alternative
      or supplemental treatment option for genital HSV-2 recurrent disease.

PMID- 18619819
TI  - Outbreak of Pseudomonas aeruginosa producing IMP-9-type metallo-beta-lactamase in
      Guangzhou, China.

PMID- 18619820
TI  - Emergence of a cefepime- and cefpirome-resistant Citrobacter freundii clinical
      isolate harbouring a novel chromosomally encoded AmpC beta-lactamase, CMY-37.
AB  - Citrobacter freundii strain 4306 was isolated from a urine specimen of a patient
      in March 2006 in Palestine. This strain showed a unique multidrug resistance
      phenotype, as it was resistant both to 7-alpha-methoxy- and oxyimino
      cephalosporins, including cefepime, cefpirome and monobactams, in addition to
      quinolones, streptomycin and trimethoprim/sulfamethoxazole. Clavulanic acid did
      not act synergistically with cephalosporins by the double-disk synergy test.
      Molecular characterisation showed that the resistance to 7-alpha-methoxy- and
      oxyimino-cephalosporins was due to a novel AmpC beta-lactamase, designated CMY
      37, with an isoelectric point of approximately 9.0. CMY-37 is a variant of C.
      freundii chromosomal AmpC enzymes with at least seven amino acid substitutions.
      One of these substitutions, L316I, is located within the R2 loop that is
      considered the hotspot region responsible for the extended substrate spectrum in
      class C beta-lactamases. The blaCMY-37 gene was cloned and expressed in
      Escherichia coli TG1. CMY-37 is chromosomally encoded and is not associated with
      ISEcp1-like element. Phylogenetic analysis suggested that CMY-37 is the origin of
      many plasmid-mediated AmpC beta-lactamases. This study highlights the emergence
      of cefepime and cefpirome resistance in C. freundii owing to a new type of AmpC
      beta-lactamase.

PMID- 18619821
TI  - Formation and recovery of a cell sheet by a particle monolayer with the surface
      roughness.
AB  - We studied the topographical effect of roughness displayed by a closely packed
      particle monolayer on formation of a cell monolayer (cell sheet). Particle
      monolayers were prepared by Langmuir-Blodgett deposition using particles, which
      were 527nm (SA053) and 1270nm (SA127) in diameter. Human umbilical vein
      endothelial cells (HUVECs) were seeded at a high density (2.0 x10(5)cells/cm(2))
      onto particle monolayers. It was found that cells gradually became into contact
      with adjacent cells on the SA053 monolayer and the formed cell sheet could be
      readily detached from the particle monolayer by gentle pipetting. On the other
      hand, cells adhering onto the tissue culture polystyrene (TCPS) and the SA127
      particle monolayer were difficult to peel off. At a low cell seeding density
      (5.0x10(4)cells/cm(2)), pre-coating with bovine plasma fibronectin (FN) allowed
      cell growth on an SA053 particle monolayer, and a confluent monolayer was able to
      be peeled as a cell sheet from the particle monolayer just by pipetting. By
      immunostaining of human fibronectin, we found that fibronectin was secreted and
      concentrated onto the substrate side of a cell sheet. The obtained cell sheet
      adhered and grew on the TCPS again within 20min.

PMID- 18619822
TI  - Living together: the marine amoeba Thecamoeba hilla Schaeffer, 1926 and its
      endosymbiont Labyrinthula sp.
AB  - Two protists isolated simultaneously from the same sample of gill tissue of
      Psetta maxima (L.) were identified as Thecamoeba hilla Schaeffer, 1926 and
      Labyrinthula sp. A Labyrinthula strain (LTH) derived from a mixed culture of both
      organisms was well established in a short time, while subcultures of T. hilla
      continued to be associated with Labyrinthula cells despite all efforts to
      eliminate them. Ultrastructural examination, repeated several times in the course
      of long-lasting subculturing of amoebae, revealed that trophozoites of T. hilla
      host in their cytoplasm multiplying labyrinthulid cells. Comparison of SSU rDNA
      sequences of the Labyrinthula strain LTH and those from labyrinthulid
      endosymbionts from T. hilla verified the assumption that the extra- and intra
      cellularly multiplying Labyrinthula cells are identical organisms. The
      association of the marine amoeba T. hilla and Labyrinthula sp. displayed signs of
      mutualistic symbiosis.

PMID- 18619823
TI  - Premaxillary movements in cyprinodontiform fishes: an unusual protrusion
      mechanism facilitates "picking" prey capture.
AB  - Premaxillary protrusion is hypothesized to confer a number of feeding advantages
      to teleost fishes; however, most proposed advantages relate to enhanced stealth
      or suction production during prey capture. Cyprinodontiformes exhibit an unusual
      form of premaxillary protrusion where the descending process of the premaxilla
      does not rotate anteriorly to occlude the sides of the open mouth during prey
      capture. Instead, the premaxilla is protruded such that it gives the impression
      of a beak during prey capture. We quantified premaxillary kinematics during
      feeding in four cyprinodontiform taxa and compared them with three percomorph
      taxa to identify any performance consequences of this protrusion mechanism.
      Individual prey capture events were recorded using digital high-speed video at
      250-500 frames per second (n >or= 4 individuals, >or= 4 strikes per individual).
      Species differed in the timing of movement and the maximum displacement of the
      premaxilla during the gape cycle and in the contribution of the premaxilla to jaw
      closing. Cyprinodontiform taxa produced less premaxillary protrusion than the
      percomorph taxa, and were consistently slower in the time to maximum gape.
      Further, it appears cyprinodontiforms can alter the contribution of the
      premaxilla to mouth closure on an event-specific basis. We were able to
      demonstrate that, within at least one species, this variability is associated
      with the location of the prey (bottom vs. water column). Cyprinodontiform upper
      jaw movements likely reflect increased dexterity associated with a foraging
      ecology where prey items are "picked" from a variety of locations: the bottom,
      water column, or surface. We postulate that dexterity requires slow, precisely
      controlled jaw movements; thus, may be traded off for some aspects of suction
      feeding performance, such as protrusion distance and speed.

PMID- 18619824
TI  - Efficacy of clinical guideline implementation to improve the appropriateness of
      chest physiotherapy prescription among inpatients with community-acquired
      pneumonia.
AB  - BACKGROUND: Although there is no strong evidence of benefit, chest physiotherapy
      (CP) seems to be commonly used in simple pneumonia. CP requires equipment and
      frequently involves the assistance of a respiratory therapist, engendering a
      significant medical workload and cost. AIM: To measure and compare the efficacy
      of two modalities of chest physiotherapy (CP) guideline implementation on the
      appropriateness of CP prescription among patients hospitalised for community
      acquired pneumonia (CAP). PATIENTS AND METHODS: We measured the CP prescription
      rate and duration in all consecutive CAP inpatients admitted in a division of
      general internal medicine at an urban teaching community hospital during three
      consecutive one-year time periods: (1) before any guideline implementation; (2)
      after a passive implementation by medical grand rounds and guideline diffusion
      through mailing; (3) after adding a one-page reminder in the CAP patient's
      medical chart highlighting our recommendations. Death and recurrent
      hospitalisation rates within one year after hospitalisation were recorded to
      assess whether CP prescription reduction, if any, impaired patient outcomes.
      RESULTS: During the three successive phases, 127, 157, and 147 patients with
      similar characteristics were included. Among all CAP inpatients, the CP
      prescription rate decreased from 68% (86/127) to 51% (80/157), and to 48%
      (71/147), respectively (P for trend <0.01 for trend). A significant reduction in
      CP duration was observed after the active guideline implementation (12.0, 11.0,
      7.0days, respectively) and persisted after adjustment for length of stay.
      Reductions in CP prescription rate and duration were also observed among CAP
      patients with COPD CP prescription rate: 97% (30/31), 67% (24/36), 75% (35/47),
      respectively (P<0.01 for trend). The mean cost of CP per patient was reduced by
      56%, from $709 to $481, and to $309, respectively. Neither the in-hospital
      deaths, the one-year overall recurrent hospitalisation nor the one-year CAP
      specific recurrent hospitalisation significantly differed between the three
      phases. CONCLUSION: Both passive and active implementation of guidelines appear
      to improve the appropriateness of CP prescription among inpatients with CAP
      without impairing their outcomes. Restricting CP use to patients who benefit from
      this treatment might be an opportunity to decrease CAP medical cost and workload.

PMID- 18619825
TI  - Right ventricular systolic pressure by echocardiography as a predictor of
      pulmonary hypertension in idiopathic pulmonary fibrosis.
AB  - RATIONALE: Pulmonary hypertension (PH) commonly complicates the course of
      patients with idiopathic pulmonary fibrosis (IPF). It has a significant impact on
      outcomes and is, therefore, important to detect. OBJECTIVES: We sought to
      characterize the accuracy and performance characteristics of the right
      ventricular systolic pressure (RVSP) as estimated by echocardiography (ECHO)
      alone and in conjunction with physiologic indices in predicting the presence of
      PH in IPF patients. METHODS: Cross-sectional study of IPF patients from two large
      tertiary centers in whom both ECHO and right-heart catheterization (RHC) were
      available. MEASUREMENTS AND MAIN RESULTS: There were 110 patients with available
      ECHOs and RHCs. Estimates of RVSP were reported in 60 of these patients (54.5%)
      of whom 22 (36.6%) had PH, while 16 of the 50 patients without RVSP estimate
      (32%) had PH. Twenty-four of 60 (40%) ECHOs accurately reflected the pulmonary
      arterial systolic pressure as measured by RHC. An optimal RVSP threshold for the
      screening of PH could not be detected. When assessed in combination with various
      thresholds of PFT and 6-minute walk test (6MWT) parameters, the performance
      characteristics of the RVSP were slightly improved. CONCLUSION: The RVSP is not
      an accurate test for the assessment of PH in IPF patients. Awareness of the
      various combinations of threshold values for RVSP with and without PFT and 6MWT
      might nonetheless assist clinicians in risk stratifying IPF patients for the
      presence of PH.

PMID- 18619826
TI  - Clinical and radiological features of Mycobacterium kansasii infection and
      Mycobacterium simiae infection.
AB  - This retrospective study sought to systematically identify clinical and
      radiological features of Mycobacterium kansasii and Mycobacterium simiae
      infections. The sample included consecutive patients with a culture-positive
      diagnosis of M. simiae infection (n=102) or M. kansasii infection (n=62) derived
      from the databases of the Laboratory of Microbiology of a tertiary medical centre
      and two outpatient tuberculosis centres. Data on patient background and clinical
      features were collected, and chest radiographs were analysed. Sixty percent of
      the M. kansasii group were native born compared to 18% of the M. simiae group
      (p=0.0001). M. simiae infection was associated with a higher rate of co-morbid
      disease, including diabetes mellitus, heart disease, and malignancy. A similar
      rate of lung disease was found in both groups. Clinical symptoms were
      significantly more common in patients with M. kansasii infection. On radiological
      study, M. kansasii infection was associated with more cavitations, and M. simiae
      infection with more pulmonary infiltrates. Patients with M. simiae infection had
      a higher likelihood of middle and lower lobe disease whereas patients with M.
      kansasii infection had more upper lobe disease (p=0.001). Pleural effusions and
      lymphadenopathy were found only in the presence of M. simiae infection. We
      concluded that there are major differences in the epidemiologic features of M.
      kansasii and M. simiae infection which have important diagnostic and therapeutic
      implications.

PMID- 18619827
TI  - Feasibility and interpretation of FE(NO) measurements in asthma patients in
      general practice.
AB  - BACKGROUND: Exhaled NO (FE(NO)) is a useful biomarker for the monitoring of
      asthma control and response to therapy. However, there is a lack of data on
      FE(NO) levels and their interpretation in Primary Care asthma population
      depending on their treatment and smoking habit. Besides, the majority of current
      FE(NO) tests have been done by stationary chemiluminescence analysers whose use
      is limited to research laboratories. METHODS: FE(NO) measurements by the novel
      hand-held NO monitoring device (NIOX MINO) were made in 96 asthma patients (32
      males, mean age 53+/-12) at five local General Practices during their scheduled
      15-20 min visits for lung function assessment. RESULTS: Success rate was 78% and
      the intra-subject coefficient of variation was 8.7%. Inhaled corticosteroid
      treatment had an overall reducing effect on the FE(NO) value (30.5 [19.8-49.8])
      vs. patients not on the ICS (26.5 [19-94]) (p<0.044). FE(NO) levels in the ICS
      treated current or ex-smokers group of patients were still significantly above
      the normal values (p<0.0001). FE(NO) levels were similar in patients receiving
      ICS whether there were current, ex-smokers or non-smokers. The highest FE(NO)
      levels (94 [15.8-151]) were found in asthmatic current smokers and not receiving
      treatment with ICS. The most "normalised" FE(NO) levels (35.3 [13.5-35.3]) were
      seen in ex-smokers. CONCLUSIONS: FE(NO) measurements performed with a new hand
      held monitoring device are reproducible and feasible in General Practice in the
      majority of patients of different ages and asthma severities. A high percentage
      of patients with different severities of asthma and regardless of their treatment
      with ICS and current smoking habit (current and/or ex-smokers) had highly
      elevated FE(NO) values, suggesting that their current therapy was possibly
      insufficient to control the underlying degree of airway inflammation and asthma
      symptoms.

PMID- 18619828
TI  - Does correction of exercise-induced desaturation by O(2) always improve exercise
      tolerance in COPD? A preliminary study.
AB  - BACKGROUND: This study sought to investigate whether correction of exercise
      induced desaturation by oxygen supply (O(2)) systematically improves exercise
      tolerance and cardiorespiratory adaptations in COPD patients. METHODOLOGY: Twenty
      five COPD patients [FEV(1)=52+/-2.5% pred] exhibiting exercise-induced
      desaturation performed cyclo-ergometer endurance exercise at 60%of their maximal
      workload in two randomized conditions: air vs. O(2). O(2) was adjusted to ensure
      90 < or = SpO(2) < or = 95%. Endurance time (Tlim), dyspnoea, ventilation (V
      (E)), breathing frequency (fb), tidal volume (V(T)), cardiac output (CO), heart
      rate (HR) and arterio-venous difference in oxygen (AVD) were compared between
      conditions. RESULTS: The comparison of whole group performance between conditions
      revealed no differences, but individual analysis showed that O(2) increased Tlim
      for 14 patients [+68%; p<0.01; (positive responders)], decreased it for seven [
      36%; p<0.05; (negative responders)] and induced no change for four (non
      responders). For positive responders, improved performance was supported by
      reduced dyspnoea, V (E), fb, HR and CO and increased AVD. For negative
      responders, hyperoxia resulted in increased dyspnoea and fb without change in V
      (E) or cardiovascular parameters. CONCLUSION: For comparable correction of
      exercise desaturation, O(2) does not induce similar effects on exercise responses
      in all patients. These results were confirmed in complementary study with 11
      consecutives patients at higher exercise intensity. For R+, we recorded the
      classic and expected O(2) effects on cardiorespiratory adaptations (i.e. reduced
      ventilatory demand and cardiac output). In the other group, exercise breathing
      frequency and dyspnoea were paradoxically increased despite desaturation
      correction. However, this study must be considered as pilot study, which will
      need to be confirmed in future studies conducted on a larger case series.

PMID- 18619829
TI  - Peroxisomes: minted by the ER.
AB  - Peroxisomes are one of numerous organelles in a eukaryotic cell; they are small,
      single-membrane-bound vesicles involved in cellular metabolism, particularly
      fatty acid degradation. Transport of metabolites and co-factors in and across the
      membrane is taken care of by specific transporters. Peroxisome formation and
      maintenance has been debated for a long time: opinions swinging from autonomous
      to ER-derived organelles. Only recently it has been established firmly that the
      site of origin of peroxisomes is the ER. It implies that a new branch of the
      endomembrane system is open to further characterization.

PMID- 18619830
TI  - The effects of aeration rate on generated compost quality, using aerated static
      pile method.
AB  - To determine the most appropriate composting process in an active municipal solid
      waste system, an experiment was carried out using a nested design method with
      three aeration rates. During each aeration rate, parameters such as temperature,
      pH, EC, carbon-to-nitrogen ratio, NO(3)-N, nitrogen, potassium and phosphorous
      were measured and the efficiency of different composting processes was evaluated.
      The result of this study showed that the lower and medium aeration rates had a
      significant impact on nitrogen, carbon-to-nitrogen ratio and temperature profile,
      while higher aeration rates led to higher EC values. Furthermore, the
      thermophilic phase lasted 13, 9 and 4 weeks for the aeration rates of 0.4, 0.6
      and 0.9 L min(-1)kg(-1), respectively. Accordingly, it was concluded that
      starting at a rate of 0.6 L min(-1)kg(-1) during first 2 months (about 9 weeks)
      of the process and continuing at a rate of 0.4 L min(-1)kg(-1)until the end of
      composting process would result in lower energy consumption.

PMID- 18619831
TI  - Pt-Pb nanowire array electrode for enzyme-free glucose detection.
AB  - Pt-Pb nanowire array was directly synthesized by electrochemical deposition of Pt
      Pb alloy into the pores of microporous polycarbonate template and subsequent
      chemical etching of the template. The morphology and the composition of the Pt-Pb
      nanowires were characterized by scanning electron microscopy (SEM) and X-ray
      photoelectron spectroscopy (XPS), respectively. Cyclic voltammetry (CV) was used
      to evaluate the electrochemical performance of the Pt-Pb nanowire array electrode
      (Pt-PbNAE). Direct glucose oxidation on Pt-PbNAE was investigated in detail by
      discussing the effect of the structure and materials of the electrode on
      electrocatalytic oxidation of glucose. As a result, we found that the Pt-PbNAE
      with a three-dimensional structure exhibited high electrocatalytic activity to
      glucose oxidation in neutral condition and could be used for the development of
      nonenzymatic glucose sensor. To effectively avoid the interference coming from
      ascorbic acid, a negative potential of -0.20V was chosen for glucose detection,
      and the sensitivity of the sensor to glucose oxidation was 11.25 microAmM(-1)cm(
      2) with a linearity up to 11 mM, and a detection limit of 8 microM (signal-to
      noise ratio of 3).

PMID- 18619832
TI  - High expression of indoleamine 2,3-dioxygenase gene in prostate cancer.
AB  - Arginase 2, inducible- and endothelial-nitric-oxide synthase (iNOS and eNOS),
      indoleamine 2,3-dioxygenase (IDO) and TGF-beta, might impair immune functions in
      prostate cancer (PCA) patients. However, their expression was not comparatively
      analysed in PCA and benign prostatic hyperplasia (BPH). We evaluated the
      expression of these genes in PCA and BPH tissues. Seventy-six patients (42 BPH,
      34 PCA) were enrolled. Arginase 2, eNOS and iNOS gene expression was similar in
      BPH and PCA tissues. TGF-beta1 gene expression was higher in BPH than in PCA
      tissues (p=0.035). IDO gene expression was more frequently detectable (p=0.00007)
      and quantitatively higher (p=0.00001) in PCA tissues than in BPH. IDO protein,
      expressed in endothelial cells from both BPH and PCA, was detectable in tumour
      cells in PCA showing evidence of high specific gene expression. In these
      patients, IDO gene expression correlated with kynurenine/tryptophan ratio in
      sera. Thus high expression of IDO gene is specifically detectable in PCA.

PMID- 18619833
TI  - Anti-herpetic and anti-inflammatory activities of two new synthetic 22,23
      dihydroxylated stigmastane derivatives.
AB  - Stromal keratitis resulting from ocular infection with Herpes simplex virus type
      1 (HSV-1) is a common cause of blindness. This report investigates the antiviral
      and anti-inflammatory properties of two new synthetic stigmastane analogs in the
      experimental model of HSV-1-induced ocular disease in mice. (22S,23S)-22,23
      dihydroxystigmast-4-en-3-one (1) and (22S,23S)-22,23-dihydroxystigmasta-1,4-dien
      3-one (2) exhibited anti-HSV-1 activity in vitro and ameliorated the signs of
      murine herpetic stromal keratitis (HSK), although none of the compounds showed
      antiviral activity in vivo. We discuss that the improvement of HSK could be due
      to an immunomodulatory effect of both compounds.

PMID- 18619834
TI  - Diagnostic precision of carcinoembryonic antigen in the detection of recurrence
      of colorectal cancer.
AB  - INTRODUCTION: The aim of the study was to evaluate the diagnostic precision of
      serum carcinoembryonic antigen (CEA) in the detection of local or distant
      recurrence following resectional surgery for colon and rectal cancer. METHODS:
      Quantitative meta-analysis was performed on 20 studies, comparing serum CEA with
      radiological imaging and/or pathology in detecting colorectal cancer (CRC)
      recurrence in 4285 patients. The cut-off for a 'positive' CEA ranged from 3 to 15
      ng/ml between the various studies. Sensitivity, specificity and diagnostic odds
      ratio (DOR) were calculated for each study. Summary receiver operating
      characteristic curves (SROC) and sub-group analysis were undertaken. RESULTS: The
      overall sensitivity and specificity of CEA for detecting CRC recurrence was 0.64
      (95% CI: 0.61-0.67) and 0.90 (95% CI: 0.89-0.91), respectively. The area under
      the SROC curve was 0.75 (SE=0.04) and the diagnostic odds ratio was 18.44 (95%
      CI: 11.94-28.49). A CEA cut-off of 5 ng/ml yielded a higher diagnostic odds ratio
      than a cut-off of 3 ng/ml (15.5 vs. 11.1). Using meta-regression analysis the
      optimum CEA cut-off point for the best combination of sensitivity and specificity
      was 2.2 ng/ml. On sub-group analysis high quality studies, and those involving >
      or =100 patients yielded a marginal improvement in the sensitivity and
      specificity with minimal change to the SROC. CONCLUSION: Serum CEA is a test with
      high specificity but insufficient sensitivity for detecting CRC recurrence in
      isolation. A cut-off of 2.2 ng/ml may provide an ideal balance of sensitivity and
      specificity. It may be useful as a first-line surveillance investigation in
      patients during surgical follow-up based on serial CEA measurements using
      temporal trends in conjunction with clinical, radiological and/or histological
      confirmation.

PMID- 18619835
TI  - Testing of thermal properties of compost from municipal waste with a view to
      using it as a renewable, low temperature heat source.
AB  - To determine how much heat may be recovered from a composting process, first it
      is necessary to know the heat production during the high temperature phase and
      characteristic values of the thermal conductivity coefficient for compost. The
      composting process was monitored in laboratory experiments. During the high
      temperature phase an average 1136kJ/kg of heat was released (but generally it was
      around 900kJ/kg). An average of 37.4% of that heat resulted from total bio
      oxidation of organic compounds, assumed to be carbohydrates. The values of
      conductivity coefficient were from 0.150 to 0.309W/mK and depended on the
      temperature, humidity, density and age of compost.

PMID- 18619836
TI  - Removal of H2S in down-flow GAC biofiltration using sulfide oxidizing bacteria
      from concentrated latex wastewater.
AB  - A biofiltration system with sulfur oxidizing bacteria immobilized on granular
      activated carbon (GAC) as packing materials had a good potential when used to
      eliminate H(2)S. The sulfur oxidizing bacteria were stimulated from concentrated
      latex wastewater with sulfur supplement under aerobic condition. Afterward, it
      was immobilized on GAC to test the performance of cell-immobilized GAC biofilter.
      In this study, the effect of inlet H(2)S concentration, H(2)S gas flow rate, air
      gas flow rate and long-term operation on the H(2)S removal efficiency was
      investigated. In addition, the comparative performance of sulfide oxidizing
      bacterium immobilized on GAC (biofilter A) and GAC without cell immobilization
      (biofilter B) systems was studied. It was found that the efficiency of the H(2)S
      removal was more than 98% even at high concentrations (200-4000 ppm) and the
      maximum elimination capacity was about 125 g H(2)S/m(3)of GAC/h in the biofilter
      A. However, the H(2)S flow rate of 15-35 l/h into both biofilters had little
      influence on the efficiency of H(2)S removal. Moreover, an air flow rate of 5.86
      l/h gave complete removal of H(2)S (100%) in biofilter A. During the long-term
      operation, the complete H(2)S removal was achieved after 3-days operation in
      biofilter A and remained stable up to 60-days.

PMID- 18619837
TI  - Using the combined bioelectrochemical and sulfur autotrophic denitrification
      system for groundwater denitrification.
AB  - A combined bioelectrochemical and sulfur autotrophic denitrification system
      (CBSAD) was evaluated to treat a groundwater with nitrate contamination (20.9
      22.0mgNO(3)(-)-N/L). The reactor was operated continuously for several months
      with groundwater to maximize treatment efficiency under different hydraulic
      retention times (HRT) and electric currents. The denitrification rate of sulfur
      autotrophic part followed a half-order kinetics model. Moreover, the removal
      efficiency of bioelectrochemical part depended on the electric current. The
      reactor could be operated efficiently at the HRT ranged from 4.2 to 2.1h
      (corresponding nitrogen volume-loading rates varied from 0.12 to 0.24 kg N/m(3)d;
      and optimum current ranged from 30 to 1000 mA), and the NO(3)(-)-N removal rate
      ranged from 95% to 100% without NO(3)(-)-N accumulation. The pH of effluent was
      satisfactorily adjusted by bioelectrochemical part, and the sulfate concentration
      of effluent was lower than 250 mg/L, meeting the drinking water standard of China
      EPA.

PMID- 18619838
TI  - Microbial production of low molecular weight hyaluronic acid by adding hydrogen
      peroxide and ascorbate in batch culture of Streptococcus zooepidemicus.
AB  - Microbial production of low molecular weight hyaluronic acid (HA) by the addition
      of hydrogen peroxide and ascorbate during the batch culture of Streptococcus
      zooepidemicus was investigated. Hydrogen peroxide (1.0 mmol/g HA) and ascorbate
      (0.5 mmol/g HA) were added at 8h and 12h to degrade HA. With the redox
      depolymerization of HA, the HA molecular weight decreased from 1,300 kDa for the
      control to 80 kDa, and the average broth viscosity during 8-16 h decreased from
      360 mPa s for the control to 290 mPa s. The average oxygen mass transfer
      coefficient K(L)a increased from 10h(-1) for the control to 35 h(-1) and the
      average dissolved oxygen level increased from 1% of air saturation in the control
      to 10%. HA production increased from 5.0 g/L for the control to 6.5 g/L, and
      contributed to the increased redox potential and energy charge. This novel
      process not only significantly enhanced production of low molecular weight HA,
      but also improved purification efficiency due to a decreased broth viscosity. Low
      molecular weight HA finds applications in biomedical and healthcare fields.

PMID- 18619839
TI  - Pyrazole inhibitors of coactivator associated arginine methyltransferase 1
      (CARM1).
AB  - This study reports the identification and Hits to Leads optimization of
      inhibitors of coactivator associated arginine methyltransferase (CARM1). Compound
      7b is a potent, selective inhibitor of CARM1.

PMID- 18619840
TI  - Lobular neoplasia: core needle breast biopsy underestimation of malignancy in
      relation to radiologic and pathologic features.
AB  - The purpose of this study is to assess the positive predictive value (PPV) for
      malignancy of core needle biopsy (CNB) demonstrating lobular neoplasia (LN). From
      3920 CNBs, 35 (0.89%) LNs (14 atypical lobular hyperplasia - ALH - and 21 lobular
      carcinoma in situ - LCIS) were identified. Twenty-eight patients underwent
      surgical excision and seven radiologic follow-up. We describe the imaging
      findings and excision histology outcomes. We report the PPV for malignancy based
      on excision histology (n=28) and on excision or follow-up (n=35), and according
      to the histologic type, biopsy probe and guidance, lesion diameter, and BI-RADS
      category. PPV for malignancy (based on excision histology) was 46.4% (13/28) and
      PPV (based on excision or follow-up) was 37.1% (13/35). The overall rate of
      malignancy for LN was 37.1% (13/35), with a PPV for malignancy of ALH and LCIS of
      7.1% (1/14) and 57.1% (12/21), respectively (p=0.003). Estimates of the PPV for
      malignancy were: stereotactic-guided vacuum-assisted biopsy (22.7%) versus
      ultrasound-guided automated CNB (61.5%), p=0.053; lesions<20mm (31.2%) versus
      lesions>20mm (100%), p=0.043; lesions classified as BI-RADS 3 (16.7%) versus BI
      RADS 4 or 5 (41.4%), p=0.377. Underestimation of malignancy was therefore more
      likely in cases of LCIS, US-guided CNB, and lesions that were large and
      suspicious on imaging. Nevertheless, the absence of these features does not spare
      the need for surgical excision in lobular neoplasia diagnosed on CNB.

PMID- 18619841
TI  - Changing reference frames during the encoding of tactile events.
AB  - The mindless act of swatting a mosquito on the hand poses a remarkable challenge
      for the brain. Given that the primary somatosensory cortex maps skin location
      independently of arm posture [1, 2], the brain must realign tactile coordinates
      in order to locate the origin of the stimuli in extrapersonal space. Previous
      studies have highlighted the behavioral relevance of such an external mapping of
      touch, which results from combining somatosensory input with proprioceptive and
      visual cues about body posture [3-7]. However, despite the widely held assumption
      about the existence of this remapping process from somatotopic to external space
      and various findings indirectly suggesting its consequences [8-11], a
      demonstration of its changing time course and nature was lacking. We examined the
      temporal course of this multisensory interaction and its implications for tactile
      awareness in humans using a crossmodal cueing paradigm [12, 13]. What we show is
      that before tactile events are referred to external locations [12-15], a
      fleeting, unconscious image of the tactile sensation abiding to a somatotopic
      frame of reference rules performance. We propose that this early somatotopic
      "glimpse" arises from the initial feed-forward sweep of neural activity to the
      primary somatosensory cortex, whereas the later externally-based, conscious
      experience reflects the activity of a somatosensory network involving recurrent
      connections from association areas.

PMID- 18619842
TI  - Osmotic regulation of Rab-mediated organelle docking.
AB  - Osmotic gradients across organelle and plasma membranes modulate the rates of
      membrane fission and fusion; sufficiently large gradients can cause membrane
      rupture [1-6]. Hypotonic gradients applied to living yeast cells trigger prompt
      (within seconds) swelling and fusion of Saccharomyces cerevisiae vacuoles,
      whereas hypertonic gradients cause vacuoles to fragment on a slower time scale [7
      11]. Here, we analyze the influence of osmotic strength on homotypic fusion of
      isolated yeast vacuoles. Consistent with previously reported in vivo results, we
      find that decreases in osmolyte concentration increase the rate and extent of
      vacuole fusion in vitro, whereas increases in osmolyte concentration prevent
      fusion. Unexpectedly, our results reveal that osmolytes regulate fusion by
      inhibiting early Rab-dependent docking or predocking events, not late events. Our
      experiments reveal an organelle-autonomous pathway that may control organelle
      surface-to-volume ratio, size, and copy number: Decreasing the osmolyte
      concentration in the cytoplasmic compartment accelerates Rab-mediated docking and
      fusion. By altering the relationship between the organelle surface and its
      enclosed volume, fusion in turn reduces the risk of membrane rupture.

PMID- 18619844
TI  - Molecular mechanisms of epithelial-barrier disruption by Helicobacter pylori.
AB  - Intact intercellular junctions and cell-matrix contacts are important structures
      in the formation and maintenance of epithelial-barrier functions against
      microbes. The human gastric pathogen Helicobacter pylori developed a remarkable
      network of strategies to alter these epithelial cell-cell and cell-matrix
      adhesions, which are implicated in inflammation, proliferation, cell migration
      and invasive growth. This review focuses on recent findings on H. pylori-induced
      host-cell signaling. We propose a stepwise model for how H. pylori interacts with
      components of focal adhesions and intercellular tight and adherens junctions to
      disrupt the epithelial layer, providing novel insights into the pathogenesis of
      H. pylori.

PMID- 18619843
TI  - Modulation of stress and virulence in Listeria monocytogenes.
AB  - Listeria monocytogenes can respond rapidly to changing environmental conditions,
      as illustrated by its ability to transition from a saprophyte to an orally
      transmitted facultative intracellular pathogen. Differential associations between
      various alternative sigma factors and a core RNA polymerase provide a
      transcriptional mechanism for regulating bacterial gene expression that is
      crucial for survival in rapidly changing conditions. Alternative sigma factors
      are key components of complex L. monocytogenes regulatory networks that include
      multiple transcriptional regulators of stress-response and virulence genes,
      regulation of genes encoding other regulators, and regulation of small RNAs. In
      this article, the contributions of various sigma factors to L. monocytogenes
      stress response and virulence are described.

PMID- 18619845
TI  - Failure to modulate neural response to increased task demand in mild Alzheimer's
      disease: fMRI study of visuospatial processing.
AB  - Alzheimer's disease (AD) is characterized by disturbances of visuospatial
      cognition. Given that these impairments are closely related to metabolic and
      neuropathological changes, our study aimed to investigate the functional
      competency of brain regions in the visuospatial networks responsible for early
      clinical symptoms in AD using event-related functional magnetic resonance imaging
      (fMRI). Participants (13AD patients with mild symptoms and 13 age- and education
      matched controls) performed an angle discrimination task with varying task
      demand. Using a novel approach that modeled the dependency of the blood
      oxygenation level-dependent (BOLD) signal on the subject's reaction time allowed
      us to investigate task demand-dependent signal changes between the groups. Both
      groups demonstrated overlapping neural networks engaged in angle discrimination,
      including the parieto-occipital and frontal regions. In several network regions,
      AD patients showed a significantly weaker and sometimes no BOLD signal due to
      increased task demand compared with controls, demonstrating failure to modulate
      the neural response to increased task demand. A general task demand-independent
      increase of activation in AD patients compared with controls was found in right
      middle temporal gyrus. This latter finding may indicate an attempt to compensate
      for dysfunctional areas in the dorsal visual pathway. These results confirm
      deficits in visuospatial abilities, which occur early in AD, and offer new
      insights into the neural mechanisms underlying this impairment.

PMID- 18619846
TI  - Activity of two catabolic enzymes of the phosphogluconate pathway in mesquite
      roots inoculated with Azospirillum brasilense Cd.
AB  - The mesquite amargo (Prosopis articulate), one of the main nurse trees of the
      Sonoran Desert in Mexico, is responsible for major, natural re-vegetation
      processes. It exudes gluconic acid in root exudates, a favorite carbon source for
      the plant growth-promoting bacterium Azospirillum brasilense. Two enzymes,
      gluconokinase (EC 2.7.1.12) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44),
      participating in the phosphogluconate pathway, are active in the bacteria.
      Bacterial 6-phosphogluconate dehydrogenase is a constitutive enzyme, while
      gluconokinase is induced upon exposure to gluconic acid. Both enzymes are active
      in young, non-inoculated mesquite seedlings growing under hydroponic conditions.
      When A. brasilense Cd bacteria are inoculated on the root system, the roots
      exhibit much higher activity of gluconokinase, but not 6-phosphogluconate
      dehydrogenase. Mesquite roots exhibit high levels of root colonization by the
      inoculating bacteria. At the same time, and also for plants growing under sand
      culture conditions, the seedlings grew taller, greener, had longer leaves, and
      were heavier.

PMID- 18619847
TI  - Differential regulation of rice mitogen activated protein kinase kinase (MKK) by
      abiotic stress.
AB  - Mitogen activated protein kinase cascade plays a crucial role in various biotic
      and abiotic stresses, hormones, cell division and developmental processes. MAP
      kinase kinase being integral part of this cascade performs an important function
      of integrating upstream signals to mitogen activated protein kinase for further
      appropriate cellular responses. We here report cloning of five MAP kinase kinase
      members from Oryza sativa indica cultivar var. Pusa Basmati 1, namely MAP kinase
      kinases 1, 3, 4, 6 and 10-2. All these members, except MKK10-2 possess fully
      canonical motif structures of MAP kinase kinase. The deduced amino acid sequence
      showed changes at certain position within japonica and indica variety of rice.
      Analysis of transcript regulation by quantitative real time PCR revealed that
      these five members are differentially regulated by cold, heat, salinity and
      drought stresses. MAP kinase kinases 4 and 6 are strongly regulated by cold and
      salt stresses while MAP kinase kinase 1 is regulated by salt and drought
      stresses. MAP kinase kinase 10-2 is regulated only by cold stress. The study
      provides the indication of involvement of specific MAP kinase kinase in different
      abiotic stress signaling and also possible cross talks that exist during the
      signaling processes.

PMID- 18619848
TI  - Endoscopic neurovascular perspective in microvascular decompression of trigeminal
      neuralgia.
AB  - PURPOSE: To evaluate the advantages of endoscopic assistance in microvascular
      decompression (MVD) for the treatment of trigeminal neuralgia (TGN). METHODS: One
      hundred and sixty-seven patients suffering from TGN were treated by MVD from
      October 2003 to December 2006. The operating microscope was used in conjunction
      with a 30 degrees effect endoscope to diagnose neurovascular compression (NVC).
      RESULTS: The type and grade of NVC were determined in all cases. 85.26% of
      neurovascular conflicts were diagnosed with the microscope alone. An additional
      14.76% could be diagnosed with the assistance of the endoscope. 96.79% of
      patients experienced immediate relief of pain. CONCLUSIONS: MVD is a highly
      effective treatment for TGN. Endoscopes are very useful during the procedures.
      They increase the clarity of the surgical field and they enable panoramic
      visualization in areas that are blind to the direct field of view of the
      operating microscope. A significant percentage of neurovascular conflicts would
      be missed at surgery without endoscopic assistance.

PMID- 18619849
TI  - Asymmetric distribution of biotin labeling on the purple membrane.
AB  - This work examined the biotin modification of bacteriorhodopsin (BR) in the
      purple membrane (PM). The results of flash kinetic absorption measurements showed
      that photocycle was maintained in biotinylated BR. Biotinylated BR also
      maintained its photoelectric activity, as indicated by the photoelectric response
      of the bilayer lipid membrane (BLM). Atomic force microscopy (AFM) of
      stretavidiin-bound biotin revealed that biotin molecules covered both surfaces of
      the, but the amount of biotinylated BR on the extracellular (EC) surface was
      markedly higher than on the cytoplasmic (CP) surface. Further studies showed
      that, after reaction with fluorescamine (FL), biotin labeling occurred only on
      the CP surface. These results are informative for future work on bioconjugation
      of BR as well as work on oriented assembly and the design of BR-based
      photoelectric devices.

PMID- 18619850
TI  - The chemokine CXCL16 induces migration and invasion of glial precursor cells via
      its receptor CXCR6.
AB  - Chemokines are implicated in developmental and inflammatory processes in the
      brain. The transmembrane chemokine CXCL16 is produced in brain endothelial and
      reactive astroglial cells and released by shedding. Its receptor CXCR6 is
      detected during brain development highest at postnatal day 6, found in glial
      precursor cells differentiated from neural stem cells and in an A2B5-positive
      glial precursor cell line. Their stimulation by soluble CXCL16 induces the PI3
      kinase/Akt and Erk pathways resulting in the activation of the transcription
      factor AP-1. As biological responses, soluble CXCL16 upregulates its own
      receptor, increases cell proliferation, stimulates cell migration in wound
      healing and in spheroid confrontation assays. Invasion of CXCR6-positive glial
      cells into CXCL16-expressing spheroids can be blocked by sheddase inhibitors and
      CXCL16-antibody. Since CXCL16 is induced by cytokines at sites of inflammation,
      neurodegeneration, ischemia and malignant transformation, it should attract CXCR6
      positive glial precursor cells, enhance their invasion and proliferation and thus
      favor astrogliosis.

PMID- 18619851
TI  - Adaptive changes in gene expression patterns in the somatosensory cortex after
      deletion of ephrinA5.
AB  - The role of wiring molecules in circuit assembly is tested directly in
      genetically engineered animals, in which the corresponding gene has been
      selectively mutated. Minor alterations in neuronal circuits in these mutant
      animals are explained by redundancy and/or adaptive changes of other genes
      relevant for brain development. There is very little known, however, about the
      extent and nature of the compensatory molecular mechanisms. Using gene
      microarrays, we compared gene expression patterns in the somatosensory cortex of
      wild type and ephrinA5 deficient mice, which exhibit subtle, but highly
      reproducible alterations of thalamocortical projections and intrinsic cortical
      circuits. We found that between 2.2%-5.7% of all transcripts (140-373 targets)
      detected in the somatosensory cortex are differentially expressed in comparing
      wild type and ephrinA5 mutants. A gene group analysis of the annotated
      transcripts revealed that a high proportion of the dysregulated genes encode
      proteins relevant for circuit development. Finer grain analysis by in situ
      hybridization and quantitative RT-PCR revealed that 20% of the Eph/ephrin family
      genes expressed in the somatosensory cortex are up-regulated in the mutant. One
      of these genes, EphB6, was up-regulated in all cortical layers, where it is
      normally expressed. However, the ephrinA2 and EphA5 were up-regulated only in
      selected layers in the cortex of the mutant; expression levels in other layers
      did not change. These findings indicate that there is specificity of adaptive and
      compensative changes in gene expression after the mutation of a single gene
      relevant for cortical development. Our results also point to the complexity of
      interpreting phenotypes of gene knock-out animals.

PMID- 18619852
TI  - Nuclear receptor binding protein 2 is induced during neural progenitor
      differentiation and affects cell survival.
AB  - We previously identified nuclear receptor binding protein 2 (NRBP2) in a screen
      for genes induced by differentiation of neural stem/progenitor cells. Here we
      show that during embryonic mouse brain development NRBP2 was expressed in the
      walls of the third and fourth ventricles, and in the hippocampus. In the adult
      brain, Purkinje cells of the cerebellum and neurons in the CA3 region of the
      hippocampus were main sites of NRBP2 expression. Analysis of a pediatric
      medulloblastoma showed that clusters of NRBP2 positive tumor cells co-expressed
      neurofilament, but not GFAP. Thus, NRBP2 was associated with neuronal
      differentiation both in normal and malignant brain tissue. We report that NRBP2
      is a 55-60 kDa protein with mainly cytoplasmic location. In vitro, NRBP2 protein
      levels increased as neural stem/progenitor cells differentiated, and its down
      regulation by siRNA rendered neural progenitor cells more vulnerable to
      apoptosis. NRBP2 has no previously assigned function and our studies suggest a
      role for NRBP2 in neural progenitor cell survival.

PMID- 18619853
TI  - Development of pilot scale production process and characterization of a
      recombinant multiepitope malarial vaccine candidate FALVAC-1A expressed in
      Escherichia coli.
AB  - Among the four human malarial species, Plasmodium falciparum causes most of the
      mortality associated with malaria. Several approaches are being pursued to
      develop a suitable malaria vaccine since it may be the most effective weapon to
      fight against malaria. A highly immunogenic, synthetic protein consisting of 21
      epitopes from pre-erythrocytic and blood stages of P. falciparum (FALVAC-1A) was
      constructed and expressed in Escherichia coli. This vaccine candidate was highly
      immunogenic and induced protective antibodies in rabbits when produced through
      lab-scale processes in milligram quantities. In order to take this vaccine
      candidate for further clinical trial, we optimized the process for industrial
      scale production and purification. Here we describe various methods used in pilot
      scale production and characterization of FALVAC-1A. A fed-batch cultivation
      process in a bioreactor at 10-L scale was optimized to express the protein in
      high yields as inclusion bodies in E. coli cells with the recombinant plasmids.
      Methods to solubilize, capture and purify the target protein from the inclusion
      bodies were optimized and the resultant protein was >95% pure based on SDS-PAGE
      and RP-HPLC. This protein was then refolded and nativity was confirmed by Far-UV
      CD spectroscopy. Final purified protein was characterized to estimate yield,
      purity, mass and confirmed to be free of host cell proteins, nucleic acids and
      bacterial endotoxins. This study confirms that industrial scale clinical grade
      FALVAC-1A can be produced in a cost-effective manner for clinical trials.

PMID- 18619854
TI  - Vitamin D and intervention trials in prostate cancer: from theory to therapy.
AB  - Studies of vitamin D and prostate cancer have advanced rapidly from the
      hypothesis that vitamin D deficiency increases the risk of prostate cancer to
      intervention trials of vitamin D administration in clinical cancer. The hormonal
      form of vitamin D, 1,25(OH)(2)D, exerts prodifferentiating, antiproliferative,
      anti-invasive, and antimetastatic effects on prostate cells. Moreover, normal
      prostate cells synthesize 1,25(OH)(2)D from serum levels of the prohormone, 25
      hydroxyvitamin D. The autocrine synthesis of 1,25(OH)(2)D by prostatic cells
      provides a biochemical mechanism whereby vitamin D may prevent prostate cancer.
      Many prostate cancer cells have lost the ability to synthesize 1,25(OH)(2)D but
      still possess 1,25(OH)(2)D receptors. This suggests that whereas vitamin D (e.g.,
      cholecalciferol) might prevent prostate cancer, existing prostate tumors likely
      would require treatment with 1,25(OH)(2)D and/or its analogs. The major obstacle
      to the use of 1,25(OH)(2)D in patients therapeutically is the risk of
      hypercalcemia. Several maneuvers to reduce this risk, including pulse dosing and
      the use of less calcemic 1,25(OH)(2)D analogs, have been explored in Phase I-III
      clinical trials. Once merely a promise, vitamin D-based therapies for prostate
      cancer may soon be medical practice.

PMID- 18619855
TI  - Induction of Mx protein in Atlantic cod with poly I:C: immuno-cross reactive
      studies of antibodies to Atlantic salmon Mx with Atlantic cod.
AB  - A polyclonal rabbit antiserum directed against the conserved region of the
      Atlantic salmon antiviral Mx1 protein was used to detect the putative Atlantic
      cod Mx protein using Western and dot blotting. A doublet band at about 75 kDa and
      65 kDa was detected by Western blotting in kidney and spleen extracts of cod 3
      and 4 days after i.p. injection with poly I:C but not in control fish injected
      with PBS. In blood leucocyte lysates, similar immunostaining could also be
      detected in Atlantic cod weakly after injection with PBS and more intensely after
      injection with poly I:C, suggesting some constitutive expression of Mx protein by
      leucocytes. Dot blot analysis showed that the Mx protein level was significantly
      higher in spleen, kidney, liver and gill of cod at least up to 4 days after
      injection with poly I:C when compared with the PBS-injected controls.

PMID- 18619856
TI  - Spectrum of the nonstationary electromyographic signal modelled with integral
      pulse frequency modulation and its application to estimating neural drive
      information.
AB  - The spectrum of nonstationary electromyographic signal (EMG) is investigated,
      from which the error for neural drive information estimation from nonstationary
      EMG is studied in terms of signal-to-noise ratio (SNR), in analytical, numerical
      simulation, and experimental work. The signal refers to the neural drive
      information embedded within the nonstationary EMG, and noise refers to other
      portions of EMG that induce error in the estimation. The analytical expressions
      for the SNRs of force-modulated EMG with both single and multiple motor units
      (MU) are derived based on a sinusoidal integral pulse frequency modulation (IPFM)
      model. It is shown that the previously developed SNR expressions for stationary
      (unmodulated) EMG are special cases of the formulas presented here. The SNR
      results obtained from numerical simulated EMG agree very well with the analytical
      result. Results from nonstationary (modulated) surface EMG obtained from seven
      subjects also match the analytical and simulation results reasonably well. The
      results obtained from this work establish an analytical framework in studying and
      estimating the neural drive information contained in the EMG in the context of
      anisotonic and isometric contractions. Through the analytical study, the effects
      of different physiological parameters are identified, thus providing theoretical
      guidelines for developing advanced signal processing methods for nonstationary
      EMG in applications such as prosthesis control.

PMID- 18619857
TI  - Classification of amyloid deposits in diagnostic cardiac specimens by
      immunofluorescence.
AB  - BACKGROUND: At least 12 distinct forms of amyloidosis are known to involve the
      heart or great vessels. Patient treatment regimens require proper subtyping of
      amyloid deposits in small diagnostic cardiac specimens. A growing lack of
      confidence in immunohistochemical staining for subtyping amyloid has arisen
      primarily as a result of studies utilizing immunoperoxidase staining of formalin
      fixed paraffin-embedded tissue. Immunofluorescence staining on fresh frozen
      tissue is generally considered superior to immunoperoxidase staining for
      subtyping amyloid; however, this technique has not previously been reported in a
      series of cardiac specimens. METHODS: Amyloid deposits were subtyped in 17
      cardiac specimens and 23 renal specimens using an immunofluorescence panel.
      RESULTS: Amyloid deposits were successfully subtyped as AL, AH, or AA amyloid by
      immunofluorescence in 82% of cardiac specimens and 87% of renal specimens. In all
      cases, the amyloid classification was in good agreement with available clinical
      and laboratory assessments. A cross-study analysis of 163 cases of AL amyloidosis
      reveals probable systemic misdiagnosis of cardiac AL amyloidosis by the
      immunoperoxidase technique, but not by the immunofluorescence technique.
      CONCLUSIONS: Amyloid deposits can be reliably subtyped in small diagnostic
      cardiac specimens using immunofluorescence. The practical aspects of implementing
      an immunofluorescence approach are compared with those of other approaches for
      subtyping amyloid in the clinical setting.

PMID- 18619858
TI  - Cardiac tumor comprising two components including typical myxoma and atypical
      hypercellularity suggesting a malignant change.
AB  - BACKGROUND: Cardiac myxoma is a benign neoplasm and is not considered to carry a
      risk of malignant transformation. We describe a case of a cardiac tumor
      comprising typical myxoma and atypical cellular parts. METHODS AND RESULTS: A 72
      year-old woman was found to have a tumor in the left atrial chamber after
      undergoing echocardiographic investigation and so she underwent tumor excision
      surgery. The excised tumor was composed of two components with different features
      with a smooth transition from one type to the other. The apex of the tumor showed
      a gelatinous and villous appearance on gross examination, and histological
      examination revealed that the tumor cells had small oval nuclei and eosinophilic
      cytoplasm and were arranged in cords and vasoformative structures in the myxoid
      matrix. The base of the tumor appeared as a solid mass on gross examination with
      hypercellular proliferation of spindle-shaped tumor cells and intersecting
      fascicles observed histologically. Nuclear mitosis was seen in more than 10/10
      high-power fields, coagulation necrosis was prominent, and invasion of the atrial
      wall was seen. On immunohistochemistry, the tumor cells were found to be positive
      for alpha-smooth muscle actin, calretinin, and CD34, and this immunoreactivity
      was decreased at the tip. Ki-67 labeling index was increased at the apex.
      CONCLUSIONS: We diagnosed this tumor as cardiac myxoma with an atypical
      hypercellular component suggesting a malignant change. It is important to
      recognize that a cardiac myxoma could be accompanied by atypical change.

PMID- 18619860
TI  - Phylogenetic relationships within Passerida (Aves: Passeriformes): a review and a
      new molecular phylogeny based on three nuclear intron markers.
AB  - The avian clade Passerida was first identified based on DNA-DNA hybridization
      data [C.G. Sibley, J.E. Ahlquist, Phylogeny and Classification of Birds, 1990,
      Yale University Press, New Haven, CT]. Monophyly of the Passerida, with the
      exception of a few taxa, has later been corroborated in several studies; however,
      the basal phylogenetic relationships have remained poorly understood. In this
      paper, we review the current knowledge of the phylogenetic relationships within
      Passerida and present a new phylogeny based on three nuclear introns (myoglobin
      intron 2, ornithine decarboxylase introns 6 and 7, as well as beta-fibrinogen
      intron 5). Our findings corroborate recent molecular hypotheses, but also
      identify several hitherto unrecognized relationships.

PMID- 18619859
TI  - Has the 2004 revision of the International Society of Heart and Lung
      Transplantation grading system improved the reproducibility of the diagnosis and
      grading of cardiac transplant rejection?
AB  - We compared the interobserver reproducibility of the 1990 and 2004 International
      Society for Heart and Lung Transplantation (ISHLT) grading system for cardiac
      rejection. The 2004 ISHLT grading system for cardiac allograft rejection did not
      improve reproducibility partly due to pathologists' disagreement in diagnosing
      Grades 1B/1R and 3A/2R rejection. To achieve better reproducibility, better
      criteria for defining 1B/1R vs. 3A/2R rejection and markers of myocyte injury are
      needed.

PMID- 18619861
TI  - Molecular phylogeny and population structure of the codling moth (Cydia
      pomonella) in Central Europe: II. AFLP analysis reflects human-aided local
      adaptation of a global pest species.
AB  - Originally resident in southeastern Europe, the codling moth (Cydia pomonella L.)
      (Tortricidae) has achieved a nearly global distribution, being one of the most
      successful pest insect species known today. As shown in our accompanying study,
      mitochondrial genetic markers suggest a Pleistocenic splitting of Cydia pomonella
      into two refugial clades which came into secondary contact after de-glaciation.
      The actual distribution pattern shows, however, that Central European codling
      moths have experienced a geographic splitting into many strains and locally
      adapted populations, which is not reflected by their mitochondrial haplotype
      distribution. We therefore have applied, in addition to mitochondrial markers, an
      approach with a higher resolution potential at the population level, based on the
      analysis of amplification fragment length polymorphisms (AFLPs). As shown in the
      present study, AFLP markers elucidate the genetic structure of codling moth
      strains and populations from different Central European apple orchard sites.
      While individual genetic diversity within codling moth strains and populations
      was small, a high degree of genetic differentiation was observed between the
      analyzed strains and populations, even at a small geographic scale. One of the
      main factors contributing to local differentiation may be limited gene flow among
      adjacent codling moth populations. In addition, microclimatic, ecological, and
      geographic constraints also may favour the splitting of Cydia pomonella into many
      local populations. Lastly, codling moths in Central European fruit orchards may
      experience considerable selective pressure due to pest control activities. As a
      consequence of all these selective forces, today in Central Europe we see a
      patchy distribution of many locally adapted codling moth populations, each of
      them having its own genetic fingerprint. Because of the complete absence of any
      correlation between insecticide resistance and geographic or genetic distances
      among populations, AFLP markers do not have a prognostic value for predicting an
      outbreak of pesticide resistance in the field. By combining mitochondrial genetic
      data and AFLP analysis it was possible, however, to track the recent evolutionary
      history of Cydia pomonella on three different time scales: from population
      splitting in Pleistocene, to interbreeding of mitochondrial haplotypes in
      Holocene, to human-aided complete intermixing and splitting into many locally
      adapted populations in very recent times. The case of Cydia pomonella is
      reminiscent of examples of sympatric speciation and another example of a human
      induced globally successful pest species.

PMID- 18619862
TI  - Heartbeat dynamics in adrenergic blocker treated conscious beagle dogs.
AB  - INTRODUCTION: Adrenergic blockade as a treatment for chronic heart failure (CHF)
      has proved effective, but its pharmacological mechanism on CHF remains unclear.
      In the past two decades, studies on heart rate variability (HRV) have reported
      that CHF patients generally have a reduced temporal complexity in heart rate
      variability. On the other hand, adrenergic blockers have been shown to restore
      such complexity. Fractal analysis is a novel and efficient tool to explore the
      adrenergic blockade effect on HRV. This paper applies the detrended fluctuation
      analysis (DFA) and multifractal DFA (MF-DFA) methods in an attempt to understand
      the effect of adrenergic blockade on cardiac dynamics in conscious beagle dogs.
      METHODS: DFA and MF-DFA analysis are conducted on RR interval data generated from
      telemetry instrumented dogs receiving a combination of 15 mg/kg nadolol and 5
      mg/kg phenoxybenzamine orally administered at the 22nd and 34th hour in a
      parallel design (n=12). All dogs had approximately 48 h of beat-to-beat heart
      rate measurements recorded in the left ventricle. Complexity measures for
      heartbeat series are compared between the blocker and vehicle group. We also
      compute traditional statistics for HRV and spectral parameters and examine their
      correlation with fractal analysis. RESULTS: When compared to the vehicle group,
      the adrenergic blocker group had: 1) longer RR intervals (p=0.02) and lower beat
      to-beat variability (p=0.04); 2) decreased low frequency (LF) and high frequency
      (HF) power (p=0.03), and higher LF-to-HF ratio; 3) larger middle-range scaling
      exponents (p<0.01); 4) broader multifractal spectra (p=0.03) with higher dominant
      singularity indices (p=0.02). DISCUSSION: Our results show that 1) adrenergic
      blockade alters the sympathovagal balance; 2) adrenergic blockers enhance the
      complexity of the cardiac dynamics; 3) the adrenergic blockade effect on cardiac
      dynamics is primarily the attenuation of small fluctuations in RR intervals.
      Fractal analysis also has the potential to be applied to early QT diagnosis.

PMID- 18619863
TI  - Lateral epicondylitis: anatomic relationships of the extensor tendon origins and
      implications for arthroscopic treatment.
AB  - The purpose this study was to provide an understanding of the location of the
      extensor carpi radialis brevis (ECRB) and its relationship to surgically relevant
      landmarks. In part I, 20 fresh-frozen cadaveric elbows were dissected, and the
      anatomic boundaries of the ECRB origin were determined, including its
      relationship to the extensor carpi radialis longus, the extensor digitorum
      communis, the lateral epicondyle, the radiocapitellar joint, the lateral
      collateral ligament, and the elbow capsule. All measurements were made by 3
      separate investigators. Whereas the ECRB and extensor digitorum communis
      converged distal to the radiocapitellar joint, the bony origin of the ECRB was
      reliably identified beneath the distal-most aspect of the supracondylar ridge,
      with a mean dimension of 13 +/- 2 mm in length by 7 +/- 2 mm in width. Part II
      was performed on 10 separate specimens to document whether the ECRB tendon could
      be identified and released arthroscopically. In all specimens, the ECRB origin
      was safely and completely released, by use of the landmarks defined in part I.
      When the ECRB is released arthroscopically, the elbow capsule must be resected
      and the tendinous origin of the ECRB released from the top of the capitellum to
      the midline of the radiocapitellar joint.

PMID- 18619864
TI  - Repair of partial thickness rotator cuff tears: a retrospective review with
      minimum two-year follow-up.

PMID- 18619865
TI  - Biomechanical evaluation of a pre-contoured clavicle plate.
AB  - Recent attention has been focused on the operative treatment of mid-shaft
      fractures of the clavicle. This study compares the in-vitro biomechanical
      properties of a pre-formed titanium clavicle plate (Acumed) to a Synthes 3.5 mm
      limited-contact dynamic-compression (LCDC) plate using a cadaveric osteotomy
      model. An osteotomy was performed on 7 pairs of human clavicles and were randomly
      plated with either a Synthes 3.5 mm LCDC stainless steel plate or an Acumed
      titanium pre-contoured clavicle plate. After plating, specimens were tested on an
      EnduraTEC material testing apparatus for axial compression and tension strength,
      as well as torsional strength in compression and tension. Biomechanical test
      results for plated specimens are reported for the LCDC plate and the Acumed
      plate, and the 2 plates are compared. This exploratory study supports
      investigations with larger sample sizes to determine if the Acumed pre-contoured
      plate differs from the LCDC plate in biomechanical properties and the clinical
      implications of such differences.

PMID- 18619866
TI  - The fulcrum axis: a new method for determining glenoid version.
AB  - Previously applied methods for the evaluation of glenoid version did not use body
      surface landmarks; therefore, it is not possible to get information about glenoid
      version from the outside. The tip of the coracoid and the posterolateral corner
      of the acromion can easily be found on the body surface. These 2 landmarks were
      connected by a line called the fulcrum axis. After using an experimental x-ray
      technique in 143 human cadaver scapulae, 5 independent observers identified the
      fulcrum axis and the glenoid fossa twice. The resulting overall angle between the
      fulcrum axis and the glenoid fossa was 1.8 degrees (SD 4.5). The fulcrum axis may
      be used for the preoperative planning and the intraoperative evaluation of
      glenoid version while performing total shoulder arthroplasties. As the fulcrum
      axis and the plane of the glenoid fossa are approximately parallel, the fulcrum
      axis can be used to position patients for performing a true antero-posterior x
      ray.

PMID- 18619867
TI  - Variation in the position of the elbow flexion axis after total joint replacement
      with three different prostheses.
AB  - The instantaneous flexion axes in rheumatoid patients treated with a Kudo (Biomet
      UK Ltd, Swindon, UK), Capitellocondylar (Johnson & Johnson Orthopaedics Inc,
      Raynham, MA), or GSB III (Zimmer GmbH, Winterthur, Switzerland) elbow prosthesis
      were calculated using radiostereometric analysis and compared with those
      previously found in the normal elbow in vivo. Variability in the flexion axis
      position was greater in the prosthetic elbows than reported for healthy subjects.
      This was especially evident for the unlinked Kudo prosthesis, with dispersions of
      the axes up to 84.3 degrees in the frontal and 45.0 degrees in the horizontal
      plane. Corresponding values for the unlinked Capitellocondylar prosthesis were
      19.7 degrees and 20.9 degrees. The linked GSB III prosthesis was the most
      constrained, with dispersions within 15.4 degrees in the frontal and 4.6 degrees
      in the horizontal plane. The unlinked elbow prostheses displayed considerable
      axis dispersion under physiologic conditions. Implant design seems to be able to
      compensate for this to some extent, as indicated, for example, by the results of
      the Capitellocondylar prosthesis.

PMID- 18619868
TI  - Recurrent anterior dislocation after the Latarjet procedure: outcome after
      revision using a modified Eden-Hybinette operation.
AB  - We assessed the results of the modified Eden-Hybinette operation as a salvage
      procedure after failure of an index Latarjet. Outcomes, complications, and
      evidence of arthritis of the glenohumeral joint were evaluated in 46 patients.
      Thirty-four (74%) were clinically and radiologically assessed at a mean of 6.8
      years (range, 2-17 years). Good or excellent results were recorded in 27 of the
      34 patients (79%). Four patients had another dislocation, and 2 became recurrent
      dislocators. One required an arthrodesis. Thirteen complained of a sensation of
      persistent apprehension. Twenty-three (68%) returned to their predislocation
      level of sport. Two gave up sports entirely. Radiographic evidence of arthritis
      was present in 6 (18%) before revision surgery. At final review, 10 (29%) had
      glenohumeral arthritis, graded as moderate or severe in 6 patients. Recurrence
      after an initial Latarjet procedure may be successfully treated by the modified
      Eden-Hybinette procedure. Patients may still experience a sensation of
      apprehension, but this does not appear to be clinically significant.

PMID- 18619870
TI  - A lysosomal protein negatively regulates surface T cell antigen receptor
      expression by promoting CD3zeta-chain degradation.
AB  - Modulation of surface T cell antigen receptor (TCR) expression is an important
      mechanism for the regulation of immune responses and the prevention of T cell
      hyperactivation and autoimmunity. The TCR is rapidly internalized after antigen
      stimulation and then degraded in lysosomes. However, few of the molecules
      involved in this process have been identified. We demonstrate that the lysosomal
      protein LAPTM5 negatively regulated surface TCR expression by specifically
      interacting with the invariant signal-transducing CD3zeta chain and promoting its
      degradation without affecting other CD3 proteins, CD3epsilon, CD3delta, or
      CD3gamma. TCR downmodulation required the polyproline-tyrosine motifs and the
      ubiquitin-interacting motif of LAPTM5. LAPTM5 deficiency resulted in elevated TCR
      expression on both CD4(+)CD8(+) thymocytes and spleen T cells after CD3
      stimulation, as well as enhanced T cell responses in vitro and in vivo. These
      results identify a lysosomal protein important for CD3zeta degradation and
      illustrate a unique mechanism for the control of surface TCR expression and T
      cell activation.

PMID- 18619869
TI  - Engagement of the type I interferon receptor on dendritic cells inhibits T helper
      17 cell development: role of intracellular osteopontin.
AB  - Mechanisms that prevent inappropriate or excessive interleukin-17-producing T
      helper (Th17) cell responses after microbial infection may be necessary to avoid
      autoimmunity. Here, we define a pathway initiated by engagement of type I IFN
      receptor (IFNAR) expressed by dendritic cells (DC) that culminated in suppression
      of Th17 cell differentiation. IFNAR-dependent inhibition of an intracellular
      translational isoform of Osteopontin, termed Opn-i, derepressed interleukin-27
      (IL-27) secretion and prevented efficient Th17 responses. Moreover, Opn-i
      expression in DC and microglia regulated the type and intensity of experimental
      autoimmune encephalomyelitis (EAE). Mice containing DC deficient in Opn-i
      produced excessive amounts of IL-27 and developed a delayed disease characterized
      by an enhanced Th1 response compared with the dominant Th17 response of Opn
      sufficient mice. Definition of the IFNAR-Opn-i axis that controls Th17
      development provides insight into regulation of Th cell sublineage development
      and the molecular basis of type I interferon therapy for MS and other autoimmune
      diseases.

PMID- 18619871
TI  - Systemic host immuno-inflammatory response to dental extractions and
      periodontitis.
AB  - OBJECTIVES: Little is known about the host immuno-inflammatory response to dental
      extractions. The purpose of this pilot clinical study was to explore the effect
      of both periodontitis and dental extractions on the host systemic immuno
      inflammatory response. STUDY DESIGN: We recruited and collected baseline blood
      samples on 41 essentially healthy patients. A subset of 22 subjects underwent
      single (n = 11) or multiple (n = 11) tooth extractions with additional blood
      samples taken at 1 hour following single tooth extraction and at 8 and 24 hours
      following multiple tooth extractions. Samples were used for determination of an
      array of 12 cytokines known to play key roles in innate and adaptive immunity.
      RESULTS: There was no significant difference in cytokine levels between the pre-
      and post-tooth extraction samples for either extraction group for the time points
      measured. Nor was there a positive relationship between the level of any of the
      cytokines and periodontal disease status as measured by mean probing depths and
      other periodontal disease parameters. CONCLUSION: Our pilot data suggest that the
      body is well adjusted to deal with the inflammation and bacteremia associated
      with dental extractions and periodontal disease.

PMID- 18619872
TI  - The effect of changes in tPCO2 on the fractional tissue oxygen extraction--as
      measured by near-infrared spectroscopy--in neonates during the first days of
      life.
AB  - The cerebral fractional oxygen extraction (FOE) reflects the balance between
      cerebral oxygen delivery (OD) and consumption (VO(2)). PCO(2) affects the
      cerebral blood flow (CBF): hypocapnia decreases CBF and OD and increases FOE. We
      recently showed that the fractional tissue oxygen extraction (FTOE) reflects FOE
      and hypothesized that a decrease in tPCO(2) increases FTOE. In this study we
      looked at the effect of changes in tPCO(2) on FTOE. We analysed 23 measurements
      in 13 neonates with birth weight below 1500 g and need for intensive care.
      Exclusion criteria were congenital malformations or cerebral complications. The
      tissue oxygenation index (TOI), tPCO(2), mean arterial blood pressure (MABP),
      heart rate (HR) and peripheral oxygen saturation (SaO(2)) were continuously
      recorded for 4h during the first days of life and FTOE was calculated. Over the
      whole group we found a significant negative (r=-0.227) correlation between
      tPCO(2) and FTOE and a significant positive (r=0.258) correlation between tPCO(2)
      and TOI. After correction for MABP these correlations remained significant. Over
      the whole group we found a significant positive correlation between tPCO(2) and
      TOI and a significant negative correlation between tPCO(2) and FTOE, which
      remained significant after correction for MABP. This implies that tPCO(2)
      influences the cerebral oxygenation independently of MABP. We therefore believe
      that for the interpretation of cerebral oxygenation in mechanically ventilated
      neonates during the first days of life continuous measurements of tPCO(2) are
      needed. Moreover we suggest FTOE to become a continuous parameter in the clinical
      setting for the non-invasive measurement of the neonatal brain oxygenation.

PMID- 18619873
TI  - Does evidence support physiotherapy management of adult Complex Regional Pain
      Syndrome Type One? A systematic review.
AB  - OBJECTIVE: To source and critically evaluate the evidence on the effectiveness of
      Physiotherapy to manage adult CRPS-1. DESIGN: Systematic literature review.
      METHODS: Electronic databases, conference proceedings, clinical guidelines and
      text books were searched for quantitative studies on CRPS-1 in adults where
      Physiotherapy was a sole or significant component of the intervention. Data were
      extracted according to predefined criteria by two independent reviewers.
      Methodological quality was assessed using the Critical Review Form. RESULTS: The
      search strategy identified 1320 potential articles. Of these, 14 articles,
      representing 11 studies, met inclusion criteria. There were five randomised
      controlled trials, one comparative study and five case series. Methodological
      quality was dependent on study type, with randomised controlled trials being
      higher in quality. Physiotherapy treatments varied between studies and were often
      provided in combination with medical management. This did not allow for the
      'stand-alone' value of Physiotherapy to be determined. Heterogeneity across the
      studies, with respect to participants, interventions evaluated and outcome
      measures used, prevented meta-analysis. Narrative synthesis of the results, based
      on effect size, found there was good to very good quality level II evidence that
      graded motor imagery is effective in reducing pain in adults with CRPS-1,
      irrespective of the outcome measure used. No evidence was found to support
      treatments frequently recommended in clinical guidelines, such as stress loading.
      CONCLUSIONS: Graded motor imagery should be used to reduce pain in adult CRPS-1
      patients. Further, the results of this review should be used to update CRPS-1
      clinical guidelines.

PMID- 18619874
TI  - Long-term oral lacosamide in painful diabetic neuropathy: a two-year open-label
      extension trial.
AB  - OBJECTIVES: This open-label follow-on trial aimed to investigate long-term safety
      and efficacy of lacosamide in patients with painful diabetic neuropathy. METHODS:
      After 1-week baseline period, lacosamide 100mg/day was started. Each week, based
      on pain and safety assessments, doses were escalated by 100mg/day to an optimal
      level, up to a maximum of 400mg/day. Patients then entered the 20-week
      maintenance period (dose adjusted as needed). Thereafter, patients could opt to
      continue lacosamide up to about 2.5 years (extension period). RESULTS: Of the 69
      enrolled patients, 47 (68%) completed the 20-week maintenance period and elected
      to continue into the extension period; 37/69 (54%) patients were in the extension
      period for more than one year and 34/69 (49%) continued until study termination.
      The modal lacosamide dose in most patients (54%) was 400mg/day. Headache, upper
      respiratory tract infection, arthralgia, sinusitis, nasopharyngitis, and back
      pain were the most frequently reported adverse events (10% of patients).
      Significant reductions from baseline in Likert pain scores began during dose
      titration and were sustained throughout the study. Significant improvements were
      also seen in Neuropathic Pain Scale, Quality of Life scores, and Patient's Global
      Impression of Change assessment. Of 34 patients at study termination, 32 (90%)
      elected to continue with lacosamide treatment in another long-term open-label
      trial (NCT00235443). CONCLUSION: The long-term safety profile and sustained
      efficacy of lacosamide observed in this trial support its continued development
      for treatment of painful diabetic neuropathy.

PMID- 18619875
TI  - Multiband excitation pulses for hyperpolarized 13C dynamic chemical-shift
      imaging.
AB  - Hyperpolarized 13C offers high signal-to-noise ratios for imaging metabolic
      activity in vivo, but care must be taken when designing pulse sequences because
      the magnetization cannot be recovered once it has decayed. It has a short
      lifetime, on the order of minutes, and gets used up by each RF excitation. In
      this paper, we present a new dynamic chemical-shift imaging method that uses
      specialized RF pulses designed to maintain most of the hyperpolarized substrate
      while providing adequate SNR for the metabolic products. These are multiband,
      variable flip angle, spectral-spatial RF pulses that use spectral selectivity to
      minimally excite the injected prepolarized 13C-pyruvate substrate. The metabolic
      products of lactate and alanine are excited with a larger flip angle to increase
      SNR. This excitation was followed by an RF amplitude insensitive double spin-echo
      and an echo-planar flyback spectral-spatial readout gradient. In vivo results in
      rats and mice are presented showing improvements over constant flip angle RF
      pulses. The metabolic products are observable for a longer window because the low
      pyruvate flip angle preserves magnetization, allowing for improved observation of
      spatially varying metabolic reactions.

PMID- 18619877
TI  - Solvent suppression using phase-modulated binomial-like sequences and
      applications to diffusion measurements.
AB  - Two phase-modulated binomial-like pi pulses have been developed by simultaneously
      optimizing pulse durations and phases. In combination with excitation sculpting,
      both of the new binomial-like sequences outperform the well-known 3-9-19 sequence
      in selectivity and inversion width. The new sequences provide similar selectivity
      and inversion width to the W5 sequence but with significantly shorter sequence
      durations. When used in PGSTE-WATERGATE, they afford highly selective solvent
      suppression in diffusion experiments.

PMID- 18619876
TI  - Microtesla MRI of the human brain combined with MEG.
AB  - One of the challenges in functional brain imaging is integration of complementary
      imaging modalities, such as magnetoencephalography (MEG) and functional magnetic
      resonance imaging (fMRI). MEG, which uses highly sensitive superconducting
      quantum interference devices (SQUIDs) to directly measure magnetic fields of
      neuronal currents, cannot be combined with conventional high-field MRI in a
      single instrument. Indirect matching of MEG and MRI data leads to significant co
      registration errors. A recently proposed imaging method--SQUID-based microtesla
      MRI--can be naturally combined with MEG in the same system to directly provide
      structural maps for MEG-localized sources. It enables easy and accurate
      integration of MEG and MRI/fMRI, because microtesla MR images can be precisely
      matched to structural images provided by high-field MRI and other techniques.
      Here we report the first images of the human brain by microtesla MRI, together
      with auditory MEG (functional) data, recorded using the same seven-channel SQUID
      system during the same imaging session. The images were acquired at 46 microT
      measurement field with pre-polarization at 30 mT. We also estimated transverse
      relaxation times for different tissues at microtesla fields. Our results
      demonstrate feasibility and potential of human brain imaging by microtesla MRI.
      They also show that two new types of imaging equipment--low-cost systems for
      anatomical MRI of the human brain at microtesla fields, and more advanced
      instruments for combined functional (MEG) and structural (microtesla MRI) brain
      imaging--are practical.

PMID- 18619878
TI  - The effect of impermeable boundaries of arbitrary geometry on the apparent
      diffusion coefficient.
AB  - The apparent diffusion coefficient (ADC) obtained from NMR measurements is
      modelled for diffusion in a compartment restricted by an impermeable boundary.
      For a given pulse sequence, the ADC can be determined from the connected velocity
      autocorrelation function (the second-order velocity cumulant), which we show can
      be expressed as a double surface integral over the boundary, involving the
      probability for molecules to diffuse from one boundary point to another. There is
      no restriction on the geometry of the boundary. This result allows a fast
      calculation of the ADC for an arbitrary time course of the diffusion-sensitizing
      gradient. Explicit examples are given for diffusion within three basic geometries
      for different pulse sequences. The ADCs measured with the Stejskal-Tanner pulse
      sequence and a more realistic pulse sequence with slice selection gradient and
      eddy current compensation are found to yield almost identical results. The
      application of the results are discussed in relation to determination of the
      microscopic structure of brain white matter.

PMID- 18619879
TI  - A simple method of estimating sampling consistency based on free energy map
      distance.
AB  - Free energy surfaces, calculated during computer simulations, are known to be
      useful in characterizing the system of interest such as bio-molecules. However,
      it is usually very difficult to evaluate free energy from direct simulations,
      mainly because of high computational costs. Several simulation strategies,
      including replica exchange method (REM), have been developed to overcome this
      problem by providing efficient conformational sampling methods. Even with such
      efficient simulation schemes, fundamental questions concerning simulation
      convergence still remain to be resolved. In this paper, we propose to use a meta
      distance between different free energy surfaces as one of the minimal measures
      for determining simulation consistency. This method is used for examining free
      energy surfaces obtained from folding simulations of a synthetic 11-residue
      protein (1AQG) using REM.

PMID- 18619880
TI  - Bone mineral density changes after total knee arthroplasty: one-year follow-up.
AB  - The study involved analysis of differences in bone mineral density (BMD) in the
      region of knee arthroplasty in 106 female patients. BMD was assessed using dual
      energy X-ray absorptiometry in a follow-up time schedule: before surgery and 2
      weeks postoperatively (baseline), 5, 12, 24, and 48 weeks after knee joint
      arthroplasty. Four assessment regions A, B, C, and D were determined in immediate
      proximity to the arthroplasty site. A year after surgery, a decrease in BMD was
      observed in all determined regions-(9.9%, 13.8%, 9.9%, and 7.6% respectively) in
      comparison with the baseline value. The most significant BMD decrease was
      observed in the period between 5 and 12 weeks after the knee joint arthroplasty.
      In our opinion, the decrease in BMD at the knee joint arthroplasty site is a
      result of the postoperative increased bone resorption and decreased patient motor
      activity.

PMID- 18619881
TI  - Application of epidemiology to change health policy: defining age-related
      thresholds of bone mineral density for primary prevention of fracture.
AB  - In Australia, benefits for antifracture therapies have been available for
      patients with osteoporosis and a prior fracture. No benefits were available to
      those with no prior fracture. We aimed to define, in women with no prior
      fracture, age-related thresholds of bone mineral density (BMD) associated with
      fracture risk equivalent to that of women with prior fracture and osteoporosis. A
      case-control study of women (> or =50 yr) was conducted, including 291 fracture
      cases and 823 controls. BMD was measured at the proximal femur and posterior
      anterior (PA) spine. A fracture risk score (FRS) for the group with no prior
      fracture was calculated with discriminant analysis. The thresholds for equivalent
      fracture risk between those with no prior fracture and those with prior fracture
      were assessed using logistic regression. Increasing the FRS to +0.98 in women
      with no prior fracture resulted in equivalent odds of sustaining a fracture to
      those with prior fracture and osteoporosis. The corresponding T-score thresholds
      at the spine were -4.6 at 50 yr, -3.9 at 60 yr, -3.1 at 70 yr, and -2.4 at 80 yr.
      The femoral neck T-score thresholds were lower by 0.5 standard deviation. The
      high-risk individuals defined by this study should be considered for primary
      fracture prevention therapy.

PMID- 18619882
TI  - Bone mineral density in cystic fibrosis: benefit of exercise capacity.
AB  - The aim of this study was to evaluate the association between bone mineral
      density (BMD) and objective maximal exercise measurements in adults with cystic
      fibrosis (CF). Twenty-five CF patients (19 males, 6 females, mean age 25.5 yr,
      range: 17-52) underwent BMD assessment and maximal-cycle ergometer exercise
      testing. We examined the relationship between gas exchange (% peak-predicted O(2)
      uptake, CO(2) output, O(2) saturation), exercise performance (maximum power,
      exercise duration), and respiratory mechanics (tidal volume, rate) with lumbar
      spine and total proximal femur BMD. The strongest clinical correlate with BMD was
      forced expiratory volume at 1s (lumbar spine Z-score, r=0.36; total proximal
      femur Z-score, r=0.68, p<0.01). The strongest exercise correlate was % peak
      predicted O(2) uptake (lumbar spine Z-score, r=0.44, p<0.01; total proximal femur
      Z-score, r=0.59, p<0.01). There was a closer association between exercise
      parameters and total proximal femur BMD (r=0.43-0.60) than with lumbar spine BMD
      (r=0.04-0.45). Multiple regression analysis revealed VO(2) to be the strongest
      independent predictor of BMD (R(2)=0.86, p<0.001) followed by petCO(2) and body
      mass index (R(2)=0.7 and 0.5, respectively, p<0.01). Exercise appears to
      influence total proximal femur BMD more than lumbar spine BMD in CF. Exercise
      rehabilitation programs focusing on peripheral strength training may benefit
      those CF patients with low total proximal femur BMD.

PMID- 18619884
TI  - Avian influenza A H5N1 infections in cats.
AB  - Although cats had been considered resistant to disease from influenza virus
      infection, domestic cats and large felids are now known to be naturally und
      experimentally susceptible to infection with highly pathogenic avian influenza
      virus H5N1 (HPAIV H5N1). The virus causes systemic infection, lung and liver
      being the mainly affected organs. Infected cats show fever, depression, dyspnoea,
      and neurological signs, but subclinical infections have also occurred. Mostly,
      cats have been infected by direct contact with affected birds, especially by
      eating raw poultry; transmission from cat to cat may also occur. Little is known
      about the role of cats in the epidemiology of the virus. So far, no reassortment
      between avian and mammalian influenza viruses has occurred in cats, but experts
      fear that cats might give the virus an opportunity to adapt to mammals. This
      publication gives a review on avian influenza in cats with a focus on practical
      aspects for veterinarians.

PMID- 18619883
TI  - Lactate metabolism in the muscle of the crab Chasmagnathus granulatus during
      hypoxia and post-hypoxia recovery.
AB  - The present study showed that the lactate/glucose ratio in the hemolymph of
      Chasmagnathus granulatus maintained in normoxia (controls) was 4.9, suggesting
      that lactate is an important substrate for this crab. Periods of hypoxia are part
      of the biological cycle of this crab, and lactate is the main end product of
      anaerobiosis in this crab. Our hypothesis was that this lactate would be,
      therefore, used by gluconeogenic pathway or can be oxidized or excreted to the
      aquatic medium during hypoxia and post-hypoxia periods in C. granulatus. The
      concentrations of hemolymphatic lactate in animals in normoxia are high, and are
      used as an energy substrate. In hypoxia, muscle gluconeogenesis and excretion of
      lactate to the aquatic medium would contribute significantly in regulating the
      concentration of circulating lactate. Utilization of these pathways would serve
      the objective of maintaining the acid-base equilibrium of the organism. Muscle
      gluconeogenesis participates, during the recovery process, in metabolizing the
      lactate produced during the period of hypoxia. Lactate excretion to the external
      medium, was one of the strategies used to decrease the higher hemolymphatic
      lactate levels. However, oxidation of lactate in the muscle is not a main
      strategy used by this crab to metabolize lactate in the recovery periods.

PMID- 18619885
TI  - Multiple urogenital abnormalities in a Persian cat.
AB  - A 1.5-year-old female Persian cat was presented for inappetence and azotemia.
      Ultrasonography and urography revealed multiple abnormalities involving the
      genitourinary tract, including agenesis of the right kidney and ureter. Gross
      examination of the abnormal uterus revealed segmental aplasia of right caudal
      uterine horn causing cranial distension with fluid, a normal left uterine horn,
      and both normal ovaries. Microscopically, endometrial glands of the right uterine
      horn were markedly decreased in number. The right uterine horn was hemorrhagic
      suggesting estrus. This is the first report of this combination of urinary and
      uterus abnormalities in the veterinary literature.

PMID- 18619886
TI  - Treatment of 46 cats with porcine lente insulin--a prospective, multicentre
      study.
AB  - This prospective, multicentre, non-blinded, open study followed 46 cats with
      diabetes mellitus during treatment with porcine lente insulin (also known as
      porcine insulin zinc suspension, Caninsulin, Intervet) for 16+/-1 weeks
      (stabilization phase), with additional monitoring of some cats (n=23) for a
      variable period. At least three of the following were present at initial
      presentation: appropriate history of clinical signs consistent with diabetes
      mellitus, glucosuria, blood glucose greater than 15 mmol/l and fructosamine
      greater than 380 micromol/l. Insulin treatment was started at a dose rate of 0.25
      0.5 IU/kg body weight twice daily, with a maximum starting dose of 2
      IU/injection. Twenty-eight of the cats were classed as reaching clinical
      stability during the study, in 23 of these cats this was during the stabilization
      phase. Seven cats went into remission during the stabilization phase and one of
      the cats in week 56. Clinical signs of hypoglycaemia, significantly associated
      with a dose of 3 units or 0.5 IU/kg or more per cat (twice daily), were observed
      in nine of the 46 cats during the stabilization phase and concomitant biochemical
      hypoglycaemia was recorded in most cases. Biochemical hypoglycaemia, recorded in
      6% of the blood glucose curves performed during the stabilization phase, was
      significantly associated with a dose rate of 0.75 IU/kg or more twice daily. This
      further highlights the need for cautious stepwise changes in insulin dose. The
      protocol used in the present study is suitable for and easy to use in practice.
      This study confirmed the efficacy and safety of porcine lente insulin
      (Caninsulin) in diabetic cats under field conditions.

PMID- 18619887
TI  - Evaluation of pradofloxacin for the treatment of feline rhinitis.
AB  - Forty humane society cats with suspected bacterial upper respiratory infections
      (URIs) were studied in order to compare amoxycillin and pradofloxacin for
      treatment of rhinitis and describe common pathogens. Nasal discharges were
      collected prior to random placement into one of three treatment groups. Cats
      failing to initially respond were crossed to the alternate drug. Drug toxicity
      was not noted. The organisms most frequently isolated or amplified pre-treatment
      were feline herpesvirus-1 (75%), Mycoplasma species (62.5%), Bordetella species
      (47.5%), Staphylococcus species (12.5%) and Streptococcus species (10.0%). No
      differences in clinical scores between groups over time were noted. Overall
      response rates for amoxycillin at 22 mg/kg, q12 h for seven doses (10/15 cats;
      67%), pradofloxacin at 5mg/kg, q24 h for seven doses (11/13 cats; 85%), and
      pradofloxacin at 10mg/kg, q24 h for seven doses (11/12 cats; 92%) were not
      statistically significant. Results suggest that pradofloxacin can be a safe,
      efficacious therapy for some cats with suspected bacterial URI.

PMID- 18619889
TI  - [A contribution to a study of apoptosis of hematopoietic stem cells CD34+ by flow
      cytometry before and after cryopreservation].
AB  - Apoptosis represents a particular form of programmed cell death which appears in
      all the damaged cells and potentially hazardous. It plays a crucial role in the
      development of multicellular organisms by assuring and maintaining the cellular
      homeostasis. Thus, apoptosis intervenes not only in the normal process of
      organisms' development but also in immune defence and in cancerous cells
      detection. Indeed, any blockage in the program of the apoptotic machinery would
      be responsible of some neurodegenerative and auto-immune diseases and could play
      a crucial role in different steps of carcinogenesis. Some researchers were very
      interested in studying apoptosis in hematopoietic stem cells CD34+ which could be
      intended to be reinfused to patients suffering from malignant diseases. They have
      noted that kinetic study of apoptosis of the hematopoietic stem cells CD34+ after
      the process of cryoconservation is also necessary. Such study permits to quantify
      the real and exact number of the viable hematopoietic stem cells CD34+ and
      therefore to eliminate such risk which would be associated with the reinfusion of
      apoptotic cells to patients. In this paper, we describe our contribution to
      hematopoietic stem cells CD34+ study by flow cytometry before and after
      cryopreservation by using annexin V as a specific probe allowing detection of
      phosphatidyl serine, one of the major features of apoptosis. But, we have noted a
      pronounced induction of apoptosis in peripheral mobilized blood compared to
      cytapheresis (after cryopreservation: 29.79% of apoptotic HSC CD34+ in peripheral
      mobilized blood but only 11.67% apoptotic HSC CD34+ in cytapheresis). Besides, we
      have noticed that hematopoietic stem cells CD34+ have had a statute of viability
      better than other mononuclear cells. These results put in value the reliability,
      the simplicity and the efficiency of flow cytometry for the analysis of apoptosis
      in hematopoietic stem cells CD34+ by following the intensity of fluorescence of
      annexin V.

PMID- 18619890
TI  - [The effect of waiting list for radiotherapy for glioblastoma].

PMID- 18619888
TI  - Asparaginyl endopeptidase from the carcinogenic liver fluke, Opisthorchis
      viverrini, and its potential for serodiagnosis.
AB  - OBJECTIVES: To isolate and characterize an asparaginyl endopeptidase from the
      carcinogenic liver fluke, Opisthorchis viverrini, and evaluate its expression
      profile, biochemical activity, and potential as an immunodiagnostic antigen.
      METHODS: The full length mRNA encoding an asparaginyl endopeptidase (family C13),
      Ov-aep-1, was isolated by immunoscreening of a cDNA bacteriophage library of
      adult O. viverrini using sera from patients infected with O. viverrini.
      Investigation of Ov-aep-1 transcripts in developmental stages of the parasite,
      and phylogenetic analysis, immunohistochemical localization, and recombinant
      protein expression and enzymology were employed to characterize the Ov-AEP-1
      protein. Immunoblotting was used to assess the potential of this enzyme for
      immunodiagnosis of human opisthorchiasis. RESULTS: Ov-AEP-1 is characteristic of
      the C13 cysteine protease family. Ov-aep-1 transcripts were detected in adult and
      juvenile worms, eggs, and metacercariae. Phylogenetic analysis indicated that Ov
      AEP-1 is closely related to homologous proteins in other trematodes. Recombinant
      Ov-AEP-1 was expressed in bacteria in inclusion bodies and refolded to a soluble
      form. Excretory-secretory (ES) products derived from adult O. viverrini and
      refolded recombinant Ov-AEP-1 both displayed catalytic activity against the
      diagnostic tripeptide substrate, Ala-Ala-Asn-aminomethylcoumarin. Rabbit
      antiserum raised to recombinant Ov-AEP-1 identified the native AEP-1 protease in
      both somatic extract and ES products of adult worms. Anti-Ov-AEP-1 IgG
      immunolocalized the anatomical site of expression to the gut of the fluke,
      implying a physiological role in digestion of food or activation of other
      digestive enzymes. Recombinant Ov-AEP-1 was recognized by serum antibodies from
      patients with opisthorchiasis but not other helminth infections, with a
      sensitivity and specificity of 85% and 100%, respectively. The positive and
      negative predictive values are 100% and 67%, respectively. CONCLUSIONS: The liver
      fluke, O. viverrini, has a gut-localized asparaginyl endopeptidase. Refolded
      recombinant Ov-AEP-1 is catalytically active and has potential for
      immunodiagnosis of human opisthorchiasis.

PMID- 18619891
TI  - Recurrent primary giant cell tumour of the proximal radius with pulmonary
      metastases.

PMID- 18619892
TI  - Damage effects of protoporphyrin IX - sonodynamic therapy on the cytoskeletal F
      actin of Ehrlich ascites carcinoma cells.
AB  - In this study, we report evidence of the damage effects of sonodynamic therapy
      (SDT) on a novel intracellular target, cytoskeletal F-actin, that has great
      importance for cancer treatment. Ehrlich ascites carcinoma (EAC) cells suspended
      in PBS were exposed to ultrasound at 1.34 MHz for up to 60s in the presence and
      absence of protoporphyrin IX (PPIX). To evaluate the polymeric state and
      distribution of actin filaments (AF) we employed FITC-Phalloidin staining. The
      percentage of cells with intact AF was decreased with 10-80 microM PPIX after
      ultrasonic exposure, while only few cells with disturbed F-actin were observed
      with 80 microM PPIX alone. The fluorescence intensity of FITC-Phalloidin labeled
      cells was detected by flow cytometry. The morphological changes of EAC cells were
      observed by scanning electron microscope (SEM). The nuclei were stained with
      Hoechst 33258 to determine apoptosis. Cytoskeletal F-actin and cell morphological
      changes were dependent on the time after SDT. Some cells suffered deformations of
      plasma membrane as blebs that reacted positively to FITC-Phalloidin at 2h after
      SDT treatment. Many of the cells showed the typically apoptotic chromatin
      fragmentation. The alterations were more significant 4h later. Our results showed
      that cytoskeletal F-actin might represent an important target for the SDT
      treatment and the observed effect on F-actin and the subsequent bleb formation
      mainly due to apoptosis formation due to the treatment.

PMID- 18619893
TI  - Continuous sleep EEG monitoring in PD patients with and without sleep attacks.
AB  - The pathogenesis of sleep attacks in Parkinson's disease (PD) is still
      unresolved. We investigated seven matched pairs of PD patients with and without a
      history of sleep attacks using continuous sleep EEG recording. According to the
      event marker altogether 12 sleep attacks were identified in three patients with a
      history of sleep attacks. All sleep attacks were characterized by NREM stage 1
      and 2 sleep, whereas no sleep onset REM episodes were recorded. Five sleep
      attacks fulfilled our criteria for microsleep episodes lasting less than 120 s.
      The cumulative duration of microsleep episodes during the day was 27.7+/-20 min
      in patients with a history of sleep attacks vs. 6.4+/-4.1 min in patients without
      a history of sleep attacks (p=0.03), i.e., the majority of microsleep episodes
      were not perceived by the patients. In summary, our study suggests that sleep
      attacks are intrusions of NREM stage 1 and 2 sleep into wakefulness and can be
      identical to microsleep episodes. Future studies should systematically address
      the awareness of short sleep episodes in patients with PD and other disorders
      with increased daytime sleepiness.

PMID- 18619894
TI  - Freezing tolerance by vesicle-mediated fructan transport.
AB  - Fructans are fructose-based polymers associated with freezing tolerance. They
      might act directly via membrane stabilization or indirectly by stimulating
      alternative cryoprotectants. Fructans and fructan biosynthetic enzymes, in
      general, are believed to be present in the vacuole. This paper draws particular
      attention to the surprising presence of fructans and fructan exohydrolase
      activity in the apoplast of cold-stressed plants. This observation raises
      questions concerning the origin of apoplastic fructans and suggests that fructans
      are transported to the apoplast by post-synthesis mechanisms, perhaps induced by
      cold. We propose a conceptual vesicle-mediated transport model for the movement
      of vacuolar fructans to the apoplast, where they could assist in stabilizing the
      plasma membrane.

PMID- 18619895
TI  - High expression of EZH2 is associated with tumor proliferation and prognosis in
      human oral squamous cell carcinomas.
AB  - Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes and
      is important in cell cycle regulation. Overexpression of EZH2 protein has been
      associated with biological malignancy of prostate cancer and several other
      cancers. The aim of the present study was to evaluate the expression of EZH2
      protein in human oral normal mucosa, dysplasia and oral squamous cell carcinoma
      (OSCC) with clinicopathological profiles. EZH2 expression was assessed by Western
      blotting and immunohistochemistry in 3 OSCC cell lines, 10 normal mucosae, 50
      dysplasias and 102 OSCCs. The labeling indices (LIs) of EZH2, Ki-67, P53, and the
      apoptotic index (AI) were evaluated by immunohistochemistry and the terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling
      (TUNEL) method. Western blot analysis detected EZH2 protein as a single band at
      91kDa in the 3 OSCC cell lines, but it was almost absent in non-tumoral oral
      mucosae. The LI of EZH2 was highest in the OSCCs, followed by the dysplasias
      (p<0.05) and normal mucosae (p<0.05) with significant difference. The LI of EZH2
      correlated with the clinical stage, tumor size, lymph node metastasis and LIs of
      Ki-67 and P53, but not with the AI in OSCCs, and inversely correlated with the
      histological differentiation of OSCCs. The survival rate calculated by the Kaplan
      Meier method revealed that OSCC patients with higher EZH2 expression showed
      poorer prognosis than those with a lower EZH2 expression (p<0.01). These results
      suggest that overexpression of EZH2 is correlated with malignant potential and
      poor prognosis in OSCCs. EZH2 might serve as a novel biomarker for predicting
      prognosis in patients with OSCCs.

PMID- 18619896
TI  - Access to and use of the Internet by South African general practitioners.
AB  - INTRODUCTION: In the developed world, doctors use the Internet to support the
      delivery of health care. Their usage patterns are explained by Rogers' Diffusion
      of Innovations. There is no knowledge of Internet usage by doctors in the
      developing world. METHODS: In July 2006, 2600 survey forms were posted in the
      first national survey of South African (SA) General Practitioners' (GPs) use of
      the Internet. A sample of non-responders was followed up. The aim was to
      determine SA GPs' Internet usage patterns, to compare them to world usage, and to
      examine them in the light of Diffusion of Innovations. RESULTS: A 10% usable
      response rate was a major weakness, but similar surveys are unlikely to be more
      representative. 89% of SA GPs have Internet access, home usage is high, and
      overall usage patterns are equivalent to the usage patterns of international
      studies. DISCUSSION: In spite of the overall technological under-development in
      South Africa, as predicted by Diffusion of Innovations, SA GPs have adopted the
      technology, and use it for health care in much the same way as their
      international counterparts. Further studies on some of the details will be
      valuable. CONCLUSION: The indications are that SA GPs will reap the benefits of
      the Internet as it continues to evolve, and translate these into improved health
      care delivery in South Africa.

PMID- 18619897
TI  - Public views of mobile medical devices and services: a US national survey of
      consumer sentiments towards RFID healthcare technology.
AB  - A 2007 national public opinion survey of 1404 Americans revealed variations in
      sentiments concerning the desirability of several mobile healthcare technologies
      based on RFID. The survey appears to be the first reasonably national public
      opinion survey of US adults concerning their attitudes towards mobile healthcare
      technology. The survey revealed high levels of interest in emergency intervention
      services, but much less so in health information and monitoring services.
      Interest in RFID personal medical technology was positively associated with high
      levels of trust in others and social support. At the same time, a small minority
      were negatively disposed towards such applications. In those cases, the negative
      sentiment appears heightened when the mobile healthcare application is offered in
      a modality attached to the body as opposed to a somewhat more physically remote
      option, i.e., attached to one's cell phone.

PMID- 18619898
TI  - Human cytomegalovirus infection in infants with prolonged neonatal jaundice.
AB  - BACKGROUND: Although human cytomegalovirus (HCMV) infection in infants has been
      associated with liver disease, the role of HCMV in infants presenting with
      prolonged neonatal jaundice is unclear as this clinical picture can be caused by
      a broad spectrum of underlying conditions. OBJECTIVES: This study aimed to
      determine a possible role for HCMV infection in infants with prolonged
      cholestatic neonatal jaundice that could facilitate the appropriate use of
      diagnostic assays and specific treatment in this condition. STUDY DESIGN: HCMV
      immunohistochemical staining was performed on liver biopsy specimens received for
      histopathological examination from 85 infants (mean age 3 months) with a clinical
      history of prolonged neonatal jaundice. HCMV serology was also performed.
      RESULTS: One infant with a histological diagnosis of HCMV hepatitis was also
      positive by immunohistochemical staining, while all other tissue specimens were
      negative for HCMV. HCMV IgG was positive in 92.3% and HCMV IgM in 39.7% of the
      infants (n=78). CONCLUSIONS: The serological results confirm the ubiquitous
      nature of HCMV with many primary infections occurring within the first year of
      life. Despite this, HCMV hepatitis was uncommon in this cohort.

PMID- 18619899
TI  - A case of congenital cardiomyopathy with acute heart failure.
AB  - A 45-year-old woman was admitted to our cardiology department for palpitations
      and dyspnoea. She had previously been investigated by echocardiography several
      times, resulting in a diagnosis of hypertrophic cardiomyopathy. However, a
      congenitally corrected transposition of the great arteries was diagnosed by our
      echocardiographic examination. The patient underwent electrophysiological
      evaluation and the accessory pathway was successfully ablated by applying
      radiofrequency pulses. This case report identifies that in patients with
      congenitally corrected transposition of the great arteries the primary diagnosis
      by echocardiography can sometimes be missed and that these patients are
      increasingly liable to develop Congestive Heart Failure with advancing age. In
      order to avoid diagnostic mistakes, more widespread dissemination of information
      about this congenital heart defect is essential.

PMID- 18619900
TI  - Very long term follow-up of cardiac resynchronization therapy: clinical outcome
      and predictors of mortality.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, left
      ventricular ejection fraction (LVEF) and survival in patients with heart failure
      and wide QRS, however, long term clinical outcome is unknown. AIMS: To identify
      predictors of mortality and evaluate the effects of CRT after long term follow
      up. METHODS: Consecutive patients treated with CRT between 1997 and 2002 were
      included. We collected clinical information from patient files. Patients who were
      still alive underwent echocardiography and clinical evaluation. RESULTS: We
      included 179 patients (median age 65.5 years, 144 male). Median follow-up for
      survival was 4.0 years. Mortality at one and five years was 15% and 53%,
      respectively. Predictors of mortality were, ischaemic heart disease (IHD), higher
      NYHA class and lower LVEF (<22.5%) at baseline, and no improvement in NYHA class
      at early follow-up. NYHA class remained stable from early to long term follow-up
      after a median of 5.1 years. In patients with non-IHD median LVEF increased
      significantly from early to long term follow-up (39% vs. 50% p=0.007).
      CONCLUSION: Predictors of mortality in patients with CRT are IHD, lower LVEF and
      higher NYHA class at baseline, and no symptomatic response to CRT. After 5 years
      follow-up, clinical effects are sustained, and in patients with non-IHD further
      improvements in LVEF are observed.

PMID- 18619901
TI  - Venous endothelial function in heart failure: comparison with healthy controls
      and effect of clinical compensation.
AB  - BACKGROUND: Endothelial function has been extensively evaluated at the arterial
      bed in several cardiovascular scenarios. Venous endothelial dysfunction, however,
      has not been thoroughly explored particularly in heart failure (HF). AIMS: To
      characterize venous endothelial function in severe HF. METHODS AND RESULTS:
      Venous endothelial function was evaluated by the dorsal hand vein technique using
      a tripod holding a linear variable differential transformer. Dorsal hand veins
      were pre-constricted with phenylephrine and dose-response curves were constructed
      after acetylcholine and sodium nitroprusside administration. Maximum vasodilator
      response to acetylcholine, a marker of endothelium-dependent venodilation, was
      significantly lower (47+/-53% versus 102+/-54%, respectively, p=0.0004) in HF
      (n=27) patients compared to healthy controls (n=20). No difference in the
      endothelium-independent venodilator response was observed (p=0.87). Maximum
      vasodilator response to acetylcholine was also significantly lower on admission
      compared to the response immediately before hospital discharge in patients with
      acute decompensated HF (p<0.01). Improvement in venous endothelial function
      paralleled weight loss (mean difference of -3.8 kg, p<0.01) and improvement in
      the 6-minute walk test (mean difference of 107 m, p<0.01). There was no
      significant change in angiotensin-converting enzyme inhibitor or beta-blocker use
      during hospital stay. CONCLUSIONS: HF patients experience marked endothelium
      dependent venous dysfunction with partial recovery during in-hospital management.

PMID- 18619903
TI  - Platelet transfusions in clinical practice at a multidisciplinary hospital in
      North India.
AB  - Specialty wise utilization pattern of platelet concentrates (PLT) over a period
      of 2 months was evaluated prospectively for appropriateness. Overall 4.87 random
      donor platelets (RDP) (total 1672) units were issued per request. A total of 1101
      RDP (66%) were transfused prophylactically against 221 requests (64.4%) while,
      571 RDP were transfused for therapeutic (requests=122, 35.6%) reasons. Twenty
      three percent of prophylactic requests and 15% of the therapeutic requisitions
      were not justified. Most common reason for unjustified prophylactic transfusion
      was unavailability of pre-transfusion platelet count. Concurrent screening of
      request forms to ensure optimized PLT usage may further decrease platelet misuse
      at our center.

PMID- 18619902
TI  - Prion safety of transfusion plasma and plasma-derivatives typically used for
      prophylactic treatment.
AB  - Reports about transfusion-related transmissions of variant Creutzfeldt-Jakob
      disease have urged the need for more information regarding the risk for prion
      contaminated units in the blood supply and the safety of transfusion plasma and
      biopharmaceuticals derived from this precious raw material. According to a
      possible epidemiological model, the risk in many European countries is the same
      or lower than that of human immunodeficiency virus. Comprehensive investigations
      have shown that the prion safety margin of both single-donor and pooled
      solvent/detergent treated transfusion plasma is high. Furthermore, prophylactic
      treatment using plasma-derivatives poses a very low risk in terms of prion
      disease despite extensive lifetime exposure.

PMID- 18619904
TI  - Pathogen reduction technology.

PMID- 18619905
TI  - Seizure emergency plans: patient results from a cross-sectional epilepsy survey.
AB  - Guidance for seizure emergency plans exists, although their impact and extent of
      use in patients with epilepsy are undetermined. This study's primary purpose was
      to measure the estimated use and content of seizure emergency plans. Secondary
      objectives included measuring: disease severity, quality of life, productivity,
      and adherence among patients with and without a plan. An online survey was
      conducted among 408 patients with epilepsy (ages 18-64) who took one or more
      antiepileptic drugs. Only 30% of patients reported having a plan, which included
      avoiding injury, notifying a physician, resting/relaxing, and seeking emergency
      assistance. Those with a plan were more likely to have experienced more seizures
      in the past year, to have missed school/work, to have incurred injury, to have
      visited the ER, to have been hospitalized, to fear additional seizures, and to
      have lost a job. Seizure emergency plans appear to be reserved for adults with
      more severe disease, but there may be clinical benefits to developing a plan for
      all adult patients with epilepsy.

PMID- 18619906
TI  - Dermatomal scratching after intramedullary quisqualate injection: correlation
      with cutaneous denervation.
AB  - Central nervous system lesions cause peripheral dysfunctions currently attributed
      to central cell death that compromises function of intact peripheral nerves.
      Injecting quisqualate (QUIS) into the rat spinal cord models spinal cord injury
      (SCI) and causes at-level scratching and self-injury. Such overgrooming was
      interpreted to model pain until patients with self-injurious scratching after SCI
      reported itch motivated scratching that was painless because of sensory loss.
      Because self-injurious scratching is difficult to explain by central mechanisms
      alone, we hypothesized that QUIS injections damage peripheral axons of at-level
      afferents. QUIS was injected into thoracic spinal cords of 18 Long-Evans rats.
      Animals were killed 3 days after overgrooming began or 14 days after injection.
      Spinal cord lesions were localized and DRG-immunolabeled for ATF-3. At-level and
      control skin samples were PGP9.5-immunabeled to quantify axons. Eighty-four
      percent of QUIS rats overgroomed. Skin in these regions had lost two-thirds of
      epidermal innervation as compared with controls (P < .001). Rats that overgroomed
      had 47% less axon-length than nongrooming rats (P = .006). The presence of ATF-3
      immunolabeled neurons within diagnosis-related groups of QUIS rats indicated
      death of afferent cell bodies. Overgrooming after QUIS injections may not be due
      entirely to central changes. As in humans, self-injurious neuropathic scratching
      appeared to require loss of protective pain sensations in addition to peripheral
      denervation. PERSPECTIVE: This study suggests that intramedullary injection of
      quisqualic acid in rats causes death of at-level peripheral as well as central
      neurons. Self-injurious dermatomal scratching that develops in spinal-injured
      rats may reflect neuropathic itch and loss of protective pain sensations.

PMID- 18619907
TI  - Cortical alpha rhythms are related to the anticipation of sensorimotor
      interaction between painful stimuli and movements: a high-resolution EEG study.
AB  - We tested whether cortical activation anticipating painful stimuli is reduced
      more by integrative processes on somatosensory painful and motor information
      relative to the same hand than when that information refers to different hands.
      In 3 conditions, visual warning stimuli were followed by visual target stimuli
      associated with an electrical painful stimulation at left index finger. In the
      Pain (control) condition, no task was required after the target stimuli. In the
      "Pain + ipsilateral movement" condition, the subjects had to perform a movement
      of the left index finger. In the "Pain + contralateral movement" condition, they
      had to perform a movement of the right index finger. Meanwhile,
      electroencephalographic data were recorded (n = 18) from 128 scalp electrodes.
      Off line, these data were spatially enhanced by surface Laplacian transformation.
      Sensorimotor cortical activation before the painful stimulation was probed by the
      percentage power reduction of alpha rhythms at approximately 8 to 12 Hz (event
      related desynchronization, ERD). Results showed that the subjects perceived a
      lower stimulus intensity in both "Pain + ipsilateral" and "Pain + contralateral"
      conditions compared with the control "Pain" condition. Furthermore, wide
      anticipatory alpha ERD (approximately 10-12 Hz) was lower in amplitude in the
      "Pain + ipsilateral" than in the "Pain + contralateral" condition. These results
      suggest that modulation of alpha rhythms is a putative physiological mechanism
      underlying anticipatory processes preceding the integration of painful and motor
      information at cortical level. Furthermore, these processes show a marked
      interference ("gating") when the sensorimotor integration refer to the same hand
      as opposed to both hands. PERSPECTIVE: We showed that cortical alpha rhythms
      preceding painful stimulation are influenced by the preparation of contralateral
      and ipsilateral finger movements. These results motivate further investigation
      for testing the hypothesis that chronic pain patients might exaggerate the
      anticipatory activation of sensorimotor cortex to negligible pain stimuli.

PMID- 18619908
TI  - Rostral ventral medulla modulation of the visceromotor reflex evoked by urinary
      bladder distension in female rats.
AB  - The present studies examined the involvement of the rostral ventral medulla (RVM)
      in modulating the visceromotor response (VMR) evoked by urinary bladder
      distension (UBD) in adult female rats. The VMR was indexed by electromyographic
      (EMG) responses of the abdominal external oblique muscle to UBD. Experiment 1
      showed that the predominant effect of electrical stimulation of the RVM in normal
      rats was to produce intensity-dependent inhibition of the VMR (54% of sites
      sampled). Facilitatory, biphasic, or no effects were obtained at the remaining
      sites. Experiment 2 showed that RVM-induced inhibition of the VMR was
      significantly attenuated by intraperitoneal (i.p.) administration of naloxone but
      not saline vehicle. In experiment 3, we examined the effect of lesions of the RVM
      in rats with inflamed bladders because previous research has shown that an
      endogenous opioid inhibitory system is engaged by bladder inflammation.
      Electrolytic lesions of the RVM but not sham lesions of the RVM significantly
      increased the VMR to graded UBD in rats with augmented VMRs induced by prior
      inflammation of the bladder. The present data suggest that the RVM can inhibit
      the VMR to UBD, acting in part via an opioid-inhibitory system, and that bladder
      inflammation can recruit the RVM to produce a net inhibitory effect on the VMR to
      UBD. PERSPECTIVE: Stimulation of the RVM resulted in inhibitory, facilitatory,
      and biphasic modulation of the visceromotor reflex to urinary bladder distension.
      Inhibitory effects of stimulation were attenuated by naloxone, and lesions of the
      RVM enhanced the VMR in rats with inflamed bladders. These data indicate an
      important role of the RVM in modulating bladder pain.

PMID- 18619909
TI  - Notochordal cells stimulate migration of cartilage end plate chondrocytes of the
      intervertebral disc in in vitro cell migration assays.
AB  - BACKGROUND CONTEXT: It was recently demonstrated that the postnatal transition
      from a notochordal to a fibrocartilaginous nucleus pulposus (NP) is accomplished
      exogenously by chondrocytes migrating from hyaline cartilage end plates (CEs)
      into the ectopic notochordal NP region. Although our previous in vivo studies
      showed evidences for the migration of CE chondrocyte from hyaline CEs into the
      notochordal NP, it is unknown whether CE chondrocytes of the intervertebral disc
      (IVD) really have a motile property. In addition, the effect of notochordal cells
      on this property has not been elucidated. PURPOSE: The purpose of this in vitro
      study was to demonstrate whether CE chondrocytes of the IVD are capable of
      migration, and whether there is any biological link between notochordal cells and
      CE chondrocytes that may regulate the CE chondrocyte migration. STUDY
      DESIGN/SETTING: In vitro cell migration assays were performed using rat IVDs.
      METHODS: Notochordal cells and chondrocytes were obtained from the NP and CE
      tissues, respectively, and were cultured separately. The different numbers of
      notochordal cells and the supernatant (conditioned medium) that contained soluble
      factors produced by notochordal cells were used to demonstrate their effects on
      the migration of CE chondrocytes. Bovine serum albumin (BSA) and lysophosphatidic
      acid (LPA) were used as negative and positive controls, respectively. RESULTS:
      Compared with BSA, LPA, notochordal cells (N=4x, 2x, 1x, and 0.5 x 10(5)), and
      its conditioned media (unconcentrated and fivefold concentrated) significantly
      increased migration of CE chondrocytes (p<.05 in all comparisons). Particularly,
      notochordal cells and its conditioned media increased migration in a number- and
      concentration-dependent manner, respectively. CONCLUSIONS: This study
      demonstrates that CE chondrocytes of the IVD are capable of migration and that
      soluble factors produced by notochordal cells stimulate the migration. These
      results provide a plausible explanation to the question of why CE chondrocytes of
      the IVD migrate into the ectopic NP region during the natural transition from the
      notochordal to fibrocartilaginous NP.

PMID- 18619910
TI  - Pregnancy after anterior spinal surgery: fertility, cesarean-section rate, and
      the use of neuraxial anesthesia.
AB  - BACKGROUND CONTEXT: Previous publications have reported results with respect to
      functional outcome and sexual function in young women after traumatic injuries to
      the pelvis. It is well known that anterior spinal surgery has the possibility of
      causing reproductive dysfunction in men. Little has been described concerning
      deleterious effects of anterior spinal surgery in women of childbearing age.
      PURPOSE: The purpose of the study was to determine the fertility, cesarean
      section rate, and the use of neuraxial anesthesia in a population of women of
      childbearing age who have undergone anterior spinal surgery. STUDY
      DESIGN/SETTING: This was a retrospective chart review combined with a telephone
      questionnaire of the patients who had undergone anterior spinal surgery by a
      single orthopedic surgeon. METHODS: Demographic data were collected from hospital
      and office records. Patients were asked if they had tried to become pregnant, if
      their pregnancy had come to term, the use of spinal or epidural anesthesia for
      that labor and delivery, and the type of delivery. RESULTS: Seventy-nine
      potential subjects were identified and 67 patients were contacted to determine
      their fertility status. Ninteen patients had tried to become pregnant after their
      anterior spinal surgery. All patients who reported that they tried to become
      pregnant were successful at having a child. Seven of the 19 women had children
      who were born by cesarean section (37%). Only two patients received an epidural
      as analgesia for their delivery. CONCLUSIONS: Although the cesarean-section rate
      appears high, it is consistent with the current obstetrical trends.
      Anesthesiologists appear less inclined to offer neuraxial anesthesia to a
      population which has undergone anterior spinal surgery.

PMID- 18619911
TI  - Antibiotic prophylaxis in spine surgery: an evidence-based clinical guideline for
      the use of prophylactic antibiotics in spine surgery.
AB  - BACKGROUND CONTEXT: The objective of the North American Spine Society's (NASS)
      Evidence-Based Clinical Guideline on Antibiotic Prophylaxis in Spine Surgery is
      to provide evidence-based recommendations on key clinical questions concerning
      the use of prophylactic antibiotics in spine surgery. The guideline is intended
      to address these questions based on the highest quality clinical literature
      available on this subject as of December 2006. The goal of the guideline
      recommendations is to assist in delivering optimum, efficacious treatment to
      prevent surgical site infection. PURPOSE: To provide an evidence-based,
      educational tool to assist spine surgeons in preventing surgical site infections.
      STUDY DESIGN: Evidence-based Clinical Guideline. METHODS: This report is from the
      Antibiotic Prophylaxis Work Group of the NASS's Evidence-Based Clinical Guideline
      Development Committee. The work group comprised multidisciplinary surgical spine
      care specialists, who were trained in the principles of evidence-based analysis.
      Each member of the group formatted a series of clinical questions to be addressed
      by the group. The final questions agreed upon by the group are the subjects of
      this report. A literature search addressing each question and using a specific
      search protocol was performed on English language references found in MEDLINE,
      EMBASE (Drugs and Pharmacology), and four additional, evidence-based, databases.
      The relevant literature was then independently rated by at least three reviewers
      using the NASS-adopted standardized levels of evidence. An evidentiary table was
      created for each of the questions. Final grades of recommendation for the answer
      to each clinical question were arrived at via Webcast meetings among members of
      the work group using standardized grades of recommendation. When Level I to Level
      IV evidence was insufficient to support a recommendation to answer a specific
      clinical question, expert consensus was arrived at by the work group through the
      modified nominal group technique and is clearly identified in the guideline.
      RESULTS: Eleven clinical questions addressed the efficacy and appropriateness of
      antibiotic prophylaxis protocols, repeat dosing, discontinuation, wound drains,
      and special considerations related to the potential impact of comorbidities on
      antibiotic prophylaxis. The responses to these 11 clinical questions are
      summarized in this document. The respective recommendations were graded by the
      strength of the supported literature which was stratified by levels of evidence.
      CONCLUSIONS: A clinical guideline addressing the use of antibiotic prophylaxis in
      spine surgery has been created using the techniques of evidence-based medicine
      and the best available evidence. This educational tool will assist spine surgeons
      in preventing surgical site infections. The entire guideline document, including
      the evidentiary tables, suggestions for future research, and references, is
      available electronically at the NASS Web site (www.spine.org) and will remain
      updated on a timely schedule.

PMID- 18619912
TI  - Cervicobulbar intramedullary lipoma.
AB  - BACKGROUND CONTEXT: Spinal lipomas not associated with spinal dysraphism are rare
      entities. Further, large medullary lipomas with intracranial extension are
      occasionally described. Most of the intradural lipomas are subpial and not really
      intramedullary. PURPOSE: Clinicians may be made aware of such a rare entity and
      its presentation. STUDY DESIGN/SETTING: An extremely rare case of medullary
      lipoma extending into posterior fossa is described in an adult, not associated
      with spinal dysraphism. METHODS: A young male presented with high cord myelopathy
      in the form of spastic quadriparesis. Radiological investigations revealed
      dorsally placed intramedullary lipoma extending into posterior fossa. RESULTS:
      Surgical excision of tumor provided satisfactory resolution of symptoms.
      CONCLUSIONS: Medullary lipomas may present with features of high cord compression
      and myelopathy. Magnetic resonance imaging remains the investigative and follow
      up modality of choice. Even when total tumor excision is not feasible, subtotal
      removal and decompression provides long lasting symptom-free survival.

PMID- 18619913
TI  - Sagittal balance influences range of motion: an in vivo study with the ProDisc-C.
AB  - BACKGROUND CONTEXT: Cervical arthroplasty is designed to maintain cervical motion
      of the functional spinal unit after cervical discectomy. The impact of the
      ProDisc-C (Synthes Spine, Paoli, PA) on in vivo kinematics and sagittal alignment
      requires further assessment. PURPOSE: The purpose of this study is to test the
      hypothesis that the ProDisc-C increases range of motion (ROM) in flexion and
      extension at the surgical level, and assess its impact on cervical alignment.
      STUDY DESIGN: Clinical study. PATIENT SAMPLE: Fifteen patients with a mean age of
      49 years were included in this study. Each patient had a single-level
      arthroplasty. Patients with multilevel arthroplasty, previous cervical spine
      surgery, and length of follow-up less than 6 months were excluded from this
      study. OUTCOME MEASURE: Lateral dynamic radiographs of the cervical spine were
      analyzed using quantitative measurement analysis (QMA) preoperatively and
      postoperatively. QMA software was also used to determine the ROM and sagittal
      translation at the surgical level. METHODS: Flexion/extension lateral radiographs
      of the cervical spine were prospectively collected and reviewed in 15 patients
      preoperatively and at early (1-3 months) and late (6-14 months) follow-up after
      placement of the ProDisc-C. Shell angle (SA) and C2-C7 Cobb angles were measured.
      Sagittal translation and ROM were calculated at each time point. Preoperative
      values were compared with early and late follow-up values using paired Student t
      tests and Pearson's correlation. RESULTS: The C2-C7 Cobb angle did not change
      significantly after surgery. Segmental ROM increased significantly from neutral
      to flexion (p=.02) and neutral to extension (p=.002) at late follow-up. SA
      correlated significantly with ROM from neutral to extension (Pearson's r=-0.55;
      p=.02) and translation from neutral to extension (Pearson's r=-0.58; p=.02).
      CONCLUSIONS: The ProDisc-C increased overall segmental ROM. A lordotic SA may be
      associated with restricted segmental ROM and translation in extension. This study
      did not detect any change in overall cervical spinal alignment after insertion of
      the device.

PMID- 18619914
TI  - Differential pattern of Cu/Zn superoxide dismutase isoforms in relation to tidal
      spatio-temporal changes in the blue mussel Mytilus edulis.
AB  - Inducible antioxidant defences in marine organisms such as mussel bivalves are
      commonly used as biomarkers of pollutant-induced oxidative stress and their
      variations proposed as one of the biological effect measurements for assessment
      of contamination impact in aquatic environments. Among them, the copper/zinc
      superoxide dismutases (Cu/Zn-SODs) are metalloenzymes which play a key role in
      the protection of cells in case of oxidative stress. In order to observe possible
      variations of an antioxidant response in relation to tidal oscillations, the
      copper/zinc superoxide dismutase activity (Cu/Zn-SOD) was characterized in the
      digestive gland and gills of blue mussels sampled at high and low shore
      throughout the tidal cycle. Determination of SOD activity was performed on gels
      after isoelectro-focusing, allowing the revelation of three isoforms. In both
      tissues, high-shore mussels exhibited a higher level of total SOD activity than
      low-shore mussels. During emersion, a decrease of total SOD activity appeared in
      digestive gland for both groups. In high-shore mussels, the less acidic form
      contributed to 75% of the total activity, the second one to 20% and the more
      acidic one to 5% in both tissues before air exposure. During emersion, the
      relative contribution of the three isoforms to the total activity was markedly
      changed with a significant decrease in intensity of the first isoform and
      parallel increases in the two other ones. After re-immersion a progressive
      recovery of proportions of SOD isoforms was observed. In low-shore mussels, the
      relative contribution of the three isoforms to the total SOD activity showed
      similar changes. The observed variations could correspond to changes in the redox
      status of the mussels during tidal oscillations.

PMID- 18619915
TI  - Carcinoid syndrome unmasked by fluoxetine, a selective serotonin reuptake
      inhibitor.

PMID- 18619916
TI  - Specifying the risk of arterial thrombosis in inflammatory bowel disease.

PMID- 18619917
TI  - Spleen enlargement on follow-up evaluation: a noninvasive predictor of
      complications of portal hypertension in cirrhosis.
AB  - BACKGROUND & AIMS: Splenomegaly is observed in most but not all patients with
      cirrhosis, and has been detected more often in patients showing complications of
      portal hypertension. We aimed to test the hypotheses that spleen enlarges over
      time in cirrhosis, and that a progressive enlargement may be associated with
      portal hypertension-related events. METHODS: A total of 127 cirrhotic patients
      (Child-Pugh, 6.7 +/- 1.7; range, 5-11), observed at our center and followed-up
      clinically, endoscopically, and with periodic abdominal ultrasound for at least 1
      year, were included. Spleen diameter was recorded at each ultrasound examination.
      The change of spleen diameter over time was calculated. The occurrence of
      clinical complications of cirrhosis on follow-up evaluation was recorded.
      RESULTS: At inclusion, spleen diameter was 14.9 +/- 3.1 cm; 83% of the patients
      had splenomegaly. Spleen was larger in patients with decompensated disease (n =
      39) versus patients with compensated disease (n = 88) (16.1 +/- 3.5 vs 14.5 +/-
      2.7; P = .012). The mean follow-up period was 53 +/- 37 months. Spleen
      progressively enlarged over time (analysis of variance, P < .0001). A total of
      46.4% of patients showed a spleen enlargement of 1 cm or more at 1 year. Over 5
      years of follow-up evaluation patients showing spleen enlargement showed a higher
      actuarial probability of esophageal varices formation (84.6% vs 16.6%; P = .001)
      and growth (63.3% vs 20.6%; P = .001). Among patients with compensated cirrhosis
      at inclusion, those showing a spleen enlargement had a higher actuarial
      probability of developing the first clinical decompensation of cirrhosis (51.1%
      vs 19.5%, P = .002). CONCLUSIONS: Spleen enlargement at follow-up evaluation
      outlines a subgroup of cirrhotic patients at higher risk of complications of
      portal hypertension. Noninvasive monitoring of spleen diameter allows a
      prognostic stratification of cirrhotic patients.

PMID- 18619918
TI  - High prevalence of functional liver derangement in visceral leishmaniasis at an
      Indian tertiary care center.
AB  - BACKGROUND & AIMS: Functional derangement of liver in visceral leishmaniasis is
      reported infrequently in the literature. Because of this, many cases are wrongly
      diagnosed and treated as hepatitis. We therefore envisaged to assess the actual
      magnitude of liver function derangement in confirmed cases of visceral
      leishmaniasis at our hospital. METHODS: All confirmed kala-azar cases presenting
      over a period of 3 years at our tertiary care hospital were included in the
      study. A detailed assessment of their liver functions was performed at the time
      of diagnosis and at various intervals until their discharge. RESULTS: A total of
      114 cases of microscopy-confirmed visceral leishmaniasis were included in the
      study. Of these, 15 (13%) had jaundice at the time of presentation, 58 (51%), 37
      (32%), 27 (24%), and 24 (21%) had increased levels of aspartate aminotransferase,
      alanine aminotransferase, alkaline phosphatase, and bilirubin, respectively.
      Eleven of the 114 cases had a fatal outcome, of whom 9 (82%) had some form of
      functional hepatic derangement. CONCLUSIONS: Thus, in our study, functional
      derangement of liver was found to be common in patients with visceral
      leishmaniasis. In some cases, hepatitis confounded and delayed the diagnosis of
      kala-azar.

PMID- 18619919
TI  - Treatment of Barrett's esophagus with high-grade dysplasia or cancer: predictors
      of surgical versus endoscopic therapy.
AB  - BACKGROUND & AIMS: Patients with Barrett's esophagus and high-grade dysplasia or
      intramucosal carcinoma are at risk of progression to invasive carcinoma. Both
      esophagectomy and endoscopic ablation are treatment options. The aim of this
      study was to identify predictors of surgical versus endoscopic therapy at a
      tertiary center. METHODS: An institutional database identified patients with
      Barrett's esophagus between 2003 and 2007. Demographic data and International
      Classification of Diseases-9th revision codes for esophagectomy, endoscopic
      ablation, as well as selected medical comorbidities were retrieved. Individual
      endoscopy, surgical, and pathology reports were reviewed. RESULTS: Among 2107
      individuals with Barrett's esophagus, 79 underwent esophagectomy and 80 underwent
      endoscopic ablation. The mean age was 63.1 +/- 10.6 years in the surgical group
      and 69.7 +/- 9.4 years in the ablation group (P < .0001). Among high-grade
      dysplasia/intramucosal carcinoma patients, 9 of 76 (12%) first seen by a
      gastroenterologist underwent esophagectomy, whereas 18 of 21 (86%) first seen by
      a surgeon underwent esophagectomy. In a logistic regression model, factors
      associated independently with esophagectomy were as follows: patient age of 60 or
      younger (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.65-14.9), cancer
      stage T1sm or greater (OR, 16.0; 95% CI, 5.60-45.6), and initial consultation
      performed by a surgeon (vs gastroenterologist) (OR, 35.1; 95% CI, 9.58-129).
      CONCLUSIONS: Patient age and cancer stage predict treatment modality for
      Barrett's esophagus with neoplasia. Treatment choice is influenced further by
      whether the initial evaluation is performed by a gastroenterologist or a surgeon.

PMID- 18619920
TI  - Fluid resuscitation in acute pancreatitis.
AB  - Acute pancreatitis is a common inflammatory disorder of the pancreas resulting in
      considerable morbidity and a mortality rate of approximately 5%. Although there
      are no pharmacologic treatments known to improve important outcomes, aggressive
      intravenous fluid resuscitation generally is recommended in all patients.
      However, few human investigations have been performed and several important
      questions have not been answered. For example, what is the optimal resuscitative
      fluid? Is there a role for colloid solutions? To what clinical marker should
      resuscitation be targeted? When is the best time to start such fluids and in
      which group of patients? This review describes the microcirculation of the
      pancreas and the pathophysiologic alterations caused by acute pancreatitis.
      Previous animal experiments are described, as are the limited human studies
      specifically addressing fluid resuscitation. Finally, current recommendations and
      goals for further investigation are highlighted. It is our hope that this review
      will stimulate interest in this often overlooked subject and lead to carefully
      designed human clinical trials using varying fluid solutions and rates, with an
      emphasis on patient monitoring and safety, in the near future.

PMID- 18619922
TI  - The use of bidirectional barbed suture in laparoscopic myomectomy and total
      laparoscopic hysterectomy.
AB  - Bidirectional barbed suture is a new design that incorporates tiny barbs spaced
      evenly along the length of the suture cut facing in opposite directions from the
      midpoint. Unlike the smooth-textured traditional suture, the bidirectional barbs
      on this new product introduce a new paradigm in which wound tension is evenly
      distributed across the length of the suture line rather than at the knotted end.
      No knots are required with bidirectional barbed suture. We present a small case
      series with bidirectional barbed suture to close myometrial defects in
      laparoscopic myomectomies and vaginal cuffs in total laparoscopic hysterectomies.
      On the basis of our early experience, we are optimistic that this new suture
      material is a potentially valuable tool for gynecologic surgeons.

PMID- 18619921
TI  - Increased immune reactivity predicts aggressive complicating Crohn's disease in
      children.
AB  - BACKGROUND & AIMS: The ability to identify children with CD who are at highest
      risk for rapid progression from uncomplicated to complicated phenotypes would be
      invaluable in guiding initial therapy. The aims of this study were to determine
      whether immune responses and/or CARD15 variants are associated with complicated
      disease phenotypes and predict disease progression. METHODS: Sera were collected
      from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti-outer
      membrane protein C, anti-Saccharomyces cerevisiae, and perinuclear antineutrophil
      cytoplasmic antibody by using enzyme-linked immunosorbent assay. Genotyping
      (Taqman MGB) was performed for 3 CARD15 variants (single nucleotide polymorphisms
      8, 12, and 13). Associations between immune responses (antibody sum and quartile
      sum score, CARD15, and clinical phenotype were evaluated. RESULTS: Thirty-two
      percent of patients developed at least 1 disease complication within a median of
      32 months, and 18% underwent surgery. The frequency of internal penetrating,
      stricturing, and surgery significantly increased (P trend < .0001 for all 3
      outcomes) with increasing antibody sum and quartile sum score. Nine percent of
      seropositive groups had internal penetrating/stricturing versus 2.9% in the
      seronegative group (P = .01). Twelve percent of seropositive groups underwent
      surgery versus 2% in the seronegative group (P = .0001). The highest antibody sum
      group (3) and quartile sum score group (4) demonstrated the most rapid disease
      progression (P < .0001). Increased hazard ratio was observed for antibody sum
      group 3 (7.8; confidence interval, 2.2-28.7), P < .002 and quartile sum score
      group 4 (11.0; confidence interval, 1.5-83.0, P < .02). CONCLUSIONS: The rate of
      complicated CD increases in children as the number and magnitude of immune
      reactivity increase. Disease progression is significantly faster in children
      expressing immune reactivity.

PMID- 18619923
TI  - Electrosurgical bipolar vessel sealing versus conventional clamping and suturing
      for total abdominal hysterectomy: a randomized trial.
AB  - STUDY OBJECTIVE: To compare the effects of bipolar vessel sealing versus
      conventional clamping and suturing in women undergoing total abdominal
      hysterectomy. DESIGN: A randomized controlled trial was performed. Patients were
      randomized to vessel sealing or conventional surgery. Postoperative pain was the
      primary outcome. An intention-to-treat analysis was performed (Canadian Task
      Force classification I). SETTING: Two Dutch teaching hospitals. PATIENTS: A total
      of 57 women undergoing abdominal hysterectomy for benign conditions. MEASUREMENTS
      AND MAIN RESULTS: During the first 3 postoperative days, patients operated on
      using vessel sealing had statistically significantly lower pain scores. The
      amount of blood loss, surgery time, complication risk, and duration of
      hospitalization were similar between both groups. Patients in the vessel-sealing
      group resumed their normal daily activities on average 8 days earlier as compared
      with the conventional group. Postoperative pelvic floor function was similar in
      both groups. CONCLUSION: The use of vessel sealing during abdominal hysterectomy
      for benign conditions appears to be associated with reduced postoperative pain
      and faster recovery.

PMID- 18619924
TI  - Endometriomas as a marker of disease severity.
AB  - STUDY OBJECTIVE: Although superficial endometriosis can be treated effectively
      and safely by most gynecologic surgeons, deep infiltrating disease (DIE) needs to
      be treated in specialist endometriosis centers. For women to be treated in the
      most appropriate setting, it is necessary to identify if they have DIE. DESIGN:
      Prospective observational study (Canadian Task Force classification II-2).
      SETTING: Dedicated pelvic pain clinic attracting both secondary and tertiary
      referrals. PATIENTS: A total of 295 women with histologically confirmed
      endometriosis. INTERVENTIONS: Prospective intraoperative data were collected to
      investigate the role of endometriomas as a marker for DIE, and in particular,
      rectosigmoid disease. MEASUREMENTS AND MAIN RESULTS: In all, 61 (21%) women had
      an endometrioma. A significantly greater proportion of women with an endometrioma
      had accompanying endometriotic disease affecting the bowel compared with women
      without an endometrioma (77% vs 21%; p<.001). A strong relationship existed
      between presence of endometrioma and posterior cul-de-sac obliteration,
      rectosigmoid disease, and involvement of the seromuscular layer of the bowel. The
      presence of an endometrioma significantly increased the probability of having
      rectosigmoid disease, with a positive likelihood ratio of 6.96 (95% CI; 4.04
      12.00). However, the absence of an endometrioma did not preclude having
      rectosigmoid disease, with a negative likelihood ratio of 0.55 (95% CI; 0.45
      0.67). CONCLUSION: Although endometriomas provide a useful marker for DIE, the
      absence of an endometrioma does not preclude the presence of DIE, although a
      significantly lower proportion of women without an endometrioma will have DIE
      when compared with women with an endometrioma.

PMID- 18619926
TI  - The diversity of current research in the red cell field.

PMID- 18619925
TI  - Rudimentary horn pregnancy diagnosed by ultrasound and treated by laparoscopy--a
      case report and review of the literature.
AB  - Pregnancy in a rudimentary horn occurs once in 76,000 pregnancies. The most
      significant threat of pregnancy in a rudimentary horn is the risk of rupture.
      With the use of ultrasound the diagnosis can be made before symptoms occur.
      Management usually consists of excision of the rudimentary horn with the
      pregnancy and the ipsilateral tube, traditionally by laparotomy. We present a
      case of an 11-week pregnancy in a rudimentary horn with a nonviable fetus
      diagnosed by ultrasound and treated with laparoscopic resection. Review of the
      literature revealed 11 cases treated successfully with laparoscopic surgery.
      Laparoscopic treatment should be considered for pregnancy in rudimentary horn
      during the first trimester.

PMID- 18619927
TI  - Microvascular complications in patients with cystic fibrosis-related diabetes
      (CFRD).
AB  - BACKGROUND: This study aims to quantitatively and qualitatively assess
      microvascular complications and their risk factors in patients with cystic
      fibrosis-related diabetes (CFRD) compared to those with type 1 diabetes mellitus
      (DM1). METHODS: 79 patients with CFRD were matched with 79 patients with DM1
      according to sex, age and duration of insulin therapy. Retinopathy, peripheral
      neuropathy, nephropathy and microalbuminuria were the microvascular complications
      assessed. Risk factors studied were: smoking, BMI, HbA1c, cholesterol,
      cholesterol/HDL ratio, diastolic and systolic blood pressure. RESULTS: Both
      groups had the same number of microvascular complications (29%). CFRD patients
      showed more microalbuminuria (21% versus 4.1%; p=0.003), while retinopathy was
      more common in patients with DM1 (24% versus 10%; p=0.044). The prevalences of
      peripheral neuropathy and nephropathy were similar. Patients with CFRD had lower
      BMI (p<0.0001), total cholesterol (p<0.0001) and HbA1c (p=0.056) levels, and a
      lower prevalence of smokers (p<0.0001). Cholesterol/HDL ratio and diastolic and
      systolic blood pressure were similar in both groups. CONCLUSIONS: The
      microvascular complications shown by patients with CFRD are similar to those seen
      in patients with DM1 but with a lower prevalence of retinopathy and a higher
      prevalence of microalbuminuria. The latter may reflect the influence of other
      cystic fibrosis-related factors on renal function.

PMID- 18619928
TI  - Optimized separation of beta-blockers with multiple chiral centers using
      capillary electrochromatography-mass spectrometry.
AB  - This work focuses on the simultaneous analysis of beta-blockers with multiple
      stereogenic centers using capillary electrochromatography-mass spectrometry (CEC
      MS) with a vancomycin stationary phase. The critical mobile phase variables
      (composition of organic solvents, acid/base ratios) as well as column temperature
      and electric field strength, effecting enantioresolution and analysis time were
      first optimized sequentially. Next, to achieve global optimum a multivariate D
      optimal design was used. Although multivariate approach did not improve
      enantioresolution any further, analysis time was significantly reduced. Under
      optimum CEC-MS conditions, all stereoisomers were resolved with resolution in the
      range 1.0-3.1 in less than 60 min with an average signal-to-noise (S/N) greater
      than 1000. The developed CEC-MS method has the potential to emerge as a screening
      method for analysis of multiple chiral compounds using a single protocol using
      the same column and mobile phase conditions, thus reducing the operation time and
      cost.

PMID- 18619929
TI  - Automated and simultaneous two-dimensional micro-high-performance liquid
      chromatographic determination of proline and hydroxyproline enantiomers in
      mammals.
AB  - A fully automated 2D-HPLC system employing a microbore-ODS column and a
      narrowbore-enantioselective column has been developed for the simultaneous
      enantiomer determination of proline, trans-4-hydroxyproline and cis-4
      hydroxyproline in mammals. As a first dimension, a monolithic ODS column of 0.53
      mm i.d. showed 3-6 times larger theoretical plate numbers than those of particle
      packed ODS columns, and the best enantioseparations were obtained by a Chiralpak
      QN-2-AX column of 1.5 mm i.d. in the second dimension (separation factors: 1.44
      1.83). The R.S.D. values for within-day and dayto-day precisions were less than
      5.8%, and the lower limits of quantitation for the D-enantiomers were 1 fmol. The
      present method was successfully applied to the determination of proline and
      hydroxyproline enantiomers in the serum and collagen-rich skin tissue. Small
      amounts of D-proline were found both in the serum (1.57 +/- 0.19 nmol/mL) and in
      the skin (0.093 +/- 0.015 nmol/mg protein), while the amounts of D-hydroxyproline
      were smaller than the lower limit of quantitation.

PMID- 18619930
TI  - Contingent valuation analysis of willingness to pay to reduce childhood obesity.
AB  - Several recent surveys have asked Americans whether they support policies to
      reduce childhood obesity. There is reason for skepticism of such surveys because
      people are not confronted with the tax costs of such policies when they are asked
      whether they support them. This paper uses contingent valuation (CV), a method
      frequently used to estimate people's willingness to pay (WTP) for goods or
      services not transacted in markets, applied to unique survey data from New York
      State to estimate the willingness to pay to reduce childhood obesity. The
      willingness to pay data correlate in predictable ways with respondent
      characteristics. The mean WTP for a 50% reduction in childhood obesity is $46.41
      (95% CI: $33.45, $59.15), which implies a total WTP by New York State residents
      of $690.6 million (95% CI: $497.7, $880.15), which is less than that implied by
      previous surveys that did not use CV methods but greater than current spending on
      policies to reduce childhood obesity and greater than the estimated savings in
      external costs. The findings provide policymakers with useful information about
      taxpayers' support for, and preferred budget for, anti-obesity policies.

PMID- 18619931
TI  - Multiple nodular lesions by colonic metastatic malignant melanoma.

PMID- 18619932
TI  - Endoscopic treatment for pill bezoars after continent ileostomy.
AB  - Difficulty intubation is the most common long-term complication after continent
      ileostomy, which can be associated with nipple valve slippage, parastomal hernia,
      stenosis. Diagnosis and management of a patient with nipple valve stricture and
      partial bowel obstruction associated with dietary supplement retention in the
      pouch reservoir is described. A 50-year-old female patient with ulcerative
      colitis and a 15-year history of continent ileostomy after total proctocolectomy
      reported 5-week symptoms of abdominal pain and difficulty in intubating the
      pouch. Pill bezoar composed of dietary supplement was found in diagnostic pouch
      endoscopy. Therapeutic pouch endoscopy was performed with balloon dilation of a
      nipple valve stenosis and retrieval of 224 dietary supplement tablets. Pill
      bezoar in the pouch is rare. However, patients with continent ileostomy should be
      advised to avoid taking hard-to-dissolve foods and medications.

PMID- 18619933
TI  - Breast reconstruction using tissue expander and TRAM flap with vascular
      enhancement procedures.
AB  - The transverse rectus abdominis myocutaneous (TRAM) flap can create a good breast
      shape, however, the patchwork-like scar obviously shows that the breast has been
      reconstructed. To reconstruct a breast without the patchwork-like appearance, we
      used a two-stage procedure using a tissue expander before transplanting a de
      epithelialised TRAM flap. In addition, to avoid fat necrosis and resorption in a
      large TRAM flap, we performed two vascular enhancement procedures, surgical delay
      and supercharging microvascular anastomosis. The surgical delay, which consisted
      of an extended skin island delay and a vascular delay, was performed when the
      tissue expander was placed under the breast skin in the first stage. As the
      extended skin island delay, zones 3 and 4 of the TRAM flap were elevated and
      silicone sheets were laid under the flaps. As the vascular delay, the deep
      inferior epigastric vessels (DIEV) on the pedicle side were ligated. In the
      second stage, the de-epithelialised TRAM flap was transferred into the expanded
      breast skin pocket. The flap was double pedicled with supercharging microvascular
      anastomosis between DIEV on the contra-pedicle side of the flap and the
      thoracodorsal vessels of the recipient site. This surgery was performed on 20
      post modified radical mastectomy patients to reconstruct large breasts without
      patchwork-like scars, and every TRAM flap survived perfectly without fat necrosis
      or resorption. All patients were satisfied with the reconstructed breasts and the
      abdominal contour without abdominal wall hernia or any other complications.

PMID- 18619934
TI  - Botulinum toxin for treatment of glandular hypersecretory disorders.
AB  - SUMMARY: The use of botulinum toxin to treat disorders of the salivary glands is
      increasing in popularity in recent years. Recent reports of the use of botulinum
      toxin in glandular hypersecretion suggest overall favourable results with minimal
      side-effects. However, few randomised clinical trials means that data are limited
      with respect to candidate suitability, treatment dosages, frequency and duration
      of treatment. We report a selection of such cases from our own department managed
      with botulinum toxin and review the current data on use of the toxin to treat
      salivary gland disorders such as Frey's syndrome, excessive salivation
      (sialorrhoea), focal and general hyperhidrosis, excessive lacrimation and chronic
      rhinitis.

PMID- 18619935
TI  - Developing a review process for Australian midwives: a report of the midwifery
      practice review project process.
AB  - OBJECTIVE: To develop a formal, robust and transparent process that supports and
      enables midwives to reflect on their own midwifery practice in relation to
      recognised professional standards and to identify, prioritise and act upon
      individual professional development and learning needs for the provision of safe,
      high quality care to women and their families within the full scope of midwifery
      practice. This process was part of a national project commissioned by the
      Australian College of Midwives and funded by the Australian Council for Safety
      and Quality in Health Care and is part of the Continuing Professional
      Development, MidPLUS program developed by the Australian College of Midwives.
      APPROACH: A multi-method, staged approach was used to develop the national
      Midwifery Practice Review process. Data to inform the development of the
      Midwifery Practice Review process was collected through a literature review,
      workshop consultations, written submissions and the pilot testing of a draft
      process. Finally, a national training workshop was undertaken to train reviewers
      to carry out reviews and to ensure the final process was validated and was
      feasible and acceptable to midwives and consumers. SETTING: Maternity care
      settings in each state and territory throughout Australia. PARTICIPANTS:
      Midwives, other health professionals and consumers of midwifery care. FINDINGS:
      The Midwifery Practice Review process was developed through research and national
      consultation prior to being validated in practice. KEY CONCLUSIONS: The Midwifery
      Practice Review process is currently being implemented and evaluated in
      Australia. IMPLICATIONS FOR PRACTICE: The Midwifery Practice Review Project
      established a national validated process for assessing the ongoing competence of
      midwives. The resulting program helps to reinforce responsibility and
      accountability in the provision of quality midwifery care through safe and
      effective practice.

PMID- 18619936
TI  - Osseous Hodgkin's lymphoma-review of literature and report of an unusual case
      presenting as a large ulcerofungating sternal mass.
AB  - Osseous involvement in Hodgkin's lymphoma is uncommon. The most common location
      is vertebral, primarily in the thoracolumbar region, followed by pelvis, ribs,
      femur, sternum, clavicle and skull in decreasing incidence. We herein illustrate
      the salient features of the disease citing a case of a disseminated Hodgkin's
      lymphoma presenting as a large ulcerofungating sternal mass mimicking chronic
      tubercular osteomyelitis. The case report highlights the importance of clinical
      suspicion of unusual presentation of lymphohematopoietic tumors of the bone
      especially in developing countries, where chronic granulomatous disease is
      preponderant.

PMID- 18619937
TI  - Relating osteon diameter to strain.
AB  - Osteon diameter is generally smaller in bone regions that experience larger
      strains. A mechanism relating osteon diameter to strain is as yet unknown. We
      propose that strain-induced osteocyte signals inhibit osteoclastic bone
      resorption. This mechanism was previously shown to produce load-aligned osteons
      in computer simulations. Now we find that it also predicts smaller osteon
      diameter for higher loads. Additionally, we find that our model predicts osteon
      development with two cutting cones, one moving up and one moving down the loading
      axis. Such 'double-ended osteons' were reported in literature as a common type of
      osteon development. Further, we find that a steep gradient in strain magnitude
      can result in an osteonal tunnel with continuous resorption along the less
      strained side, which corresponds to 'drifting osteons' reported in literature.

PMID- 18619938
TI  - Ecology, evolution, and the long-term surveillance of vector-borne Chagas
      disease: a multi-scale appraisal of the tribe Rhodniini (Triatominae).
AB  - Chagas disease incidence has sharply declined over the last decade. Long-term
      disease control will, however, require extensive, longitudinal surveillance
      systems capable of detecting (and dealing with) reinvasion-reinfestation of
      insecticide-treated dwellings by non-domiciliated triatomines. Sound surveillance
      design calls for reliable data on vector ecology, and these data must cover
      different spatial scales. We conducted a multi-scale assessment of ecological and
      evolutionary trends in members of the tribe Rhodniini, including (i) a macroscale
      analysis of Rhodniini species richness and composition patterns across the
      Americas, and (ii) a detailed, mesoscale case-study of ecological and behavioural
      trends in Rhodnius neglectus and R. nasutus. Our macroscale overview provides
      some comprehensive insights about key mechanisms/processes probably underlying
      ecological and genetic diversification in the Rhodniini. These insights translate
      into a series of testable hypotheses about current species distributions and
      their likely causes. At the landscape scale, we used geometric morphometrics to
      identify dubious specimens as either R. neglectus or R. nasutus (two near-sibling
      species), and studied palm tree populations of these two vector taxa in five
      geographical areas. The data suggest that deforestation and the associated loss
      of habitat and host diversity might increase the frequency of vector-human
      contact (and perhaps Trypanosoma cruzi infection rates in vectors). Surveillance
      in central-northeastern Brazil should prioritise deforested landscapes where
      large palm trees (e.g., Attalea, Mauritia, Copernicia, Acrocomia or Syagrus)
      occur near houses. We anticipate that, by helping define the distribution
      patterns and ecological preferences of each species, multi-scale research will
      significantly strengthen vector surveillance systems across Latin America.

PMID- 18619939
TI  - Cryptic splice site in the complementary DNA of glucocerebrosidase causes
      inefficient expression.
AB  - The low levels of human lysosomal glucocerebrosidase activity expressed in
      transiently transfected Chinese hamster ovary (CHO) cells were investigated.
      Reverse transcription PCR (RT-PCR) demonstrated that a significant portion of the
      transcribed RNA was misspliced owing to the presence of a cryptic splice site in
      the complementary DNA (cDNA). Missplicing results in the deletion of 179 bp of
      coding sequence and a premature stop codon. A repaired cDNA was constructed
      abolishing the splice site without changing the amino acid sequence. The level of
      glucocerebrosidase expression was increased sixfold. These data demonstrate that
      for maximum expression of any cDNA construct, the transcription products should
      be examined.

PMID- 18619940
TI  - Difference in polymerization and steady-state dynamics of free and gelsolin
      capped filaments formed by alpha- and beta-isoactins.
AB  - The polymerization of scallop beta-like actin is significantly slower than that
      of skeletal muscle alpha-actin. To reveal which steps of polymerization
      contribute to this difference, we estimated the efficiency of nucleation of the
      two actins, the rates of filament elongation at spontaneous and gelsolin
      nucleated polymerization and the turnover rates of the filament subunits at
      steady-state. Scallop actin nucleated nearly twice less efficient than rabbit
      actin. In actin filaments with free ends, when dynamics at the barbed ends
      overrides that at the pointed ends, the relative association rate constants of
      alpha- and beta-actin were similar, whereas the relative dissociation rate
      constant of beta-ATP-actin subunits was 2- to 3-fold higher than that of alpha
      actin. The 2- to 3-fold faster polymerization of skeletal muscle versus scallop
      Ca-actin was preserved with gelsolin-capped actin filaments when only
      polymerization at the pointed end is possible. With gelsolin-induced
      polymerization, the rate constants of dissociation of ATP-actin subunits from the
      pointed ends were similar, while the association rate constant of beta-actin to
      the pointed filament ends was twice lower than that of alpha-actin. This
      difference may be of physiological relevance for functional intracellular sorting
      of actin isoforms.

PMID- 18619941
TI  - Deltapsi and DeltapH are equivalent driving forces for proton transport through
      isolated F(0) complexes of ATP synthases.
AB  - The membrane-embedded F(0) part of ATP synthases is responsible for ion
      translocation during ATP synthesis and hydrolysis. Here, we describe an in vitro
      system for measuring proton fluxes through F(0) complexes by fluorescence changes
      of the entrapped fluorophore pyranine. Starting from purified enzyme, the F(0)
      part was incorporated unidirectionally into phospholipid vesicles. This allowed
      analysis of proton transport in either synthesis or hydrolysis direction with
      Deltapsi or DeltapH as driving forces. The system displayed a high signal-to
      noise ratio and can be accurately quantified. In contrast to ATP synthesis in the
      Escherichia coli F(1)F(0) holoenzyme, no significant difference was observed in
      the efficiency of DeltapH or Deltapsi as driving forces for H(+)-transport
      through F(0). Transport rates showed linear dependency on the driving force.
      Proton transport in hydrolysis direction was about 2400 H(+)/(s x F(0)) at
      Deltapsi of 120 mV, which is approximately twice as fast as in synthesis
      direction. The chloroplast enzyme was faster and catalyzed H(+)-transport at
      initial rates of 6300 H(+)/(s x F(0)) under similar conditions. The new method is
      an ideal tool for detailed kinetic investigations of the ion transport mechanism
      of ATP synthases from various organisms.

PMID- 18619942
TI  - Overexpression of Kir2.3 in PC12 cells resists rotenone-induced neurotoxicity
      associated with PKC signaling pathway.
AB  - Parkinson's disease (PD) can be triggered by genetic or environmental factors.
      Although the precise etiopathogenesis of the disease remains unknown, recent
      studies focusing on the K(+) channel gene have uncovered the dysfunctions in
      various K(+) channels (e.g., Kir2, Kv, K(ATP), and SKCa) that are involved in the
      pathological mechanisms underlying PD. Here we show that Kir2.3 overexpression
      can protect against rotenone-induced apoptosis in cell models in the
      neurodegenerative process, suggesting Kir2.3's general neuroprotective function.
      The protection of Kir2.3 against neurodegeneration may be associated with the
      protein kinase C (PKC) pathway, as PKC is downregulated by Kir2.3 overexpression
      and the PKC activator can reduce the protective effect of Kir2.3. Our studies
      provide an entry point for understanding the novel roles of Kir2.3 in cell models
      of PD, and they offer clues for the common mechanisms underlying different
      neurodegenerative conditions.

PMID- 18619943
TI  - Construction of a non-infectious SARS coronavirus replicon for application in
      drug screening and analysis of viral protein function.
AB  - Severe acute respiratory syndrome virus (SARS-CoV) was the causative agent of the
      SARS outbreaks in 2002-2003. A safer in vitro system is desirable for conducting
      research on SARS-CoV and to screen for antiviral drugs against the virus. Based
      on the infectious cDNA clone of rSARS-CoV-DeltaE, in which the E gene has been
      deleted, a safe non-infectious replicon was constructed by replacing the S gene
      with the enhanced green fluorescent protein (eGFP) gene. Successful replication
      was achieved as evident from continuous expression of eGFP detected by both
      fluorescence and Western blot. Treatment with antiviral drugs demonstrated that
      the replication could be significantly inhibited by 0.4 mg/ml of cysteine
      proteinase inhibitor E-64D, but not by ribavirin. The same replicons containing
      further deletion of the coding regions for non-structural proteins (nsp) 1, 2 or
      16 confirmed previous observation that nsp16, but not nsp1 or nsp2, was essential
      for efficient viral replication or transcription.

PMID- 18619944
TI  - Outer arm fucosylation of N-glycans increases in sera of hepatocellular carcinoma
      patients.
AB  - Serum glycans are promising markers for early-stage cancer detection, but the
      research remains challenging because low concentrations of serum glycoproteins
      are secreted from early-stage tumors. We have established an N-glycan profiling
      method using liquid chromatography electrospray ionization-mass spectrometry with
      high sensitive derivative, trimethyl(4-aminophenyl)ammonium chloride (TMAPA). The
      mass sensitivity of TMAPA-labeled oligosaccharides was enhanced more than 50
      times compared with 2-aminopyridine (PA) labeled oligosaccharides, and the
      analytical period was significantly shortened compared with traditional HPLC 2D
      mapping. Using this method, we found about 28 major N-linked oligosaccharides in
      human sera, and we investigated their alterations in patients who developed
      hepatocellular carcinoma (HCC). We found that outer arm fucosylation (attached
      GlcNAc via an alpha 1-3/4 linkage) in highly branched oligosaccharides increased
      significantly in sera of HCC patients. Normalizing the level of outer arm
      fucosylation by taking into account platelet concentration allowed us to
      distinguish more clearly between HCC and LC patients.

PMID- 18619945
TI  - Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved
      sequences with tolerance for wobble base-pairing.
AB  - The high genetic diversity and mutability of HIV pose a major problem for RNAi
      mediated antiviral therapy. Simultaneous targeting of multiple highly conserved
      viral sequences has been suggested for durable cross-clade inhibition. Here we
      validate the approach of co-targeting two conserved sequences in the Tat and Vif
      genes. When coexpressed as artificial microRNA from a PolII driven miR-155-based
      vector, the sequences together mediated effective and sustained inhibition of HIV
      replication without virus breakout. To understand the nature of this efficient
      control, we analyzed genome sequences of 625 HIV-1 isolates in the Los Alamos
      Sequence database. Interestingly most natural variants were capable of wobble
      binding with the Tat/Vif siRNAs. Efficient silencing of reporter luciferase
      constructs bearing these variants residues verified that the Tat/Vif sequences
      together tolerated wobble binding and mediated functional RNAi. We propose the
      rationale of targeting highly conserved HIV sequences where wobble substitutions
      permit functional RNAi for global HIV repression.

PMID- 18619946
TI  - Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein
      expression in human cancer cells.
AB  - MicroRNAs are short non-coding RNA molecules able to affect stability and/or
      translation of mRNA, thereby regulating the expression of genes involved in many
      biological processes. We report here that microRNAs miR-27a and miR-451 are
      involved in activating the expression of P-glycoprotein, the MDR1 gene product
      that confers cancer cell resistance to a broad range of chemotherapeutics. We
      showed that expressions of miR-27a and miR-451 were up-regulated in multidrug
      resistant (MDR) cancer cell lines A2780DX5 and KB-V1, as compared with their
      parental lines A2780 and KB-3-1. Treatment of A2780DX5 cells with the antagomirs
      of miR-27a or miR-451 decreased the expression of P-glycoprotein and MDR1 mRNA.
      In contrast, the mimics of miR-27a and miR-451 increased MDR1 expression in the
      parental cells A2780. The sensitivity to and intracellular accumulation of
      cytotoxic drugs that are transported by P-glycoprotein were enhanced by the
      treatment with the antagomirs of miR-27a or miR-451. Our results demonstrate for
      the first time the roles of microRNAs in the regulation of drug resistance
      mediated by MDR1/P-glycoprotein, and suggest the potential for targeting miR-27a
      and miR-451 as a therapeutic strategy for modulating MDR in cancer cells.

PMID- 18619947
TI  - Changes in the expression and subcellular localization of RARalpha in the rat
      hippocampus during postnatal development.
AB  - Retinoic acid receptors (RARs) are reported to mediate the effects of retinoid
      acid and participate in the maintenance of normal hippocampal function during
      embryonic and postnatal stages. RARalpha is the only one that has been reported
      to be continuously expressed among RARs in the CA1-CA3 areas of the hippocampus,
      at both the mRNA and the protein level. Here, we show the expression and
      subcellular localization of RARalpha in granule and pyramidal cells in various
      regions of the hippocampus during postnatal development of rats. We discovered
      that the expression level of RARalpha in postnatal hippocampal tissue gradually
      decreased over time with increasing developmental maturity of the nervous system.
      Moreover, the subcellular localization of RARalpha expression showed a phenomenon
      of intracellular translocation during the postnatal development period. This new
      discovery is inconsistent with a traditional viewpoint according to which
      RARalpha, as a nuclear transcription factor, is mainly expressed inside nucleus.
      This phenomenon suggests that RARalpha may have different actions during each
      stage of hippocampal development.

PMID- 18619948
TI  - Abnormal response of dopaminergic neurons to nicotine without perturbation of
      nicotinic receptors in alphaCGRP knock-out mice.
AB  - Alpha-calcitonin gene-related peptide (alphaCGRP) is a neuropeptide with multiple
      biological properties, including the regulation of nicotinic acetylcholine
      receptors (nAChRs). We have previously reported a reduction of somatic withdrawal
      symptoms in alphaCGRP knock-out mice exposed to chronic nicotine, leading us to
      investigate the contribution of alphaCGRP to the regulations of ventral tegmental
      area (VTA) neurons and their response to nicotine. The electrophysiological
      activity of VTA dopaminergic (DA) neurons was recorded in vivo, under anesthesia.
      These neurons displayed identical spontaneous electrophysiogical activities in
      wild-type and alphaCGRP-/- mice. However, we found that intravenous
      administration of nicotine (30 microg/kg) had no significant effect on the
      activity of DA neurons in alphaCGRP-/- mice, whereas it induced a doubling of the
      firing rate in wild-type animals. A higher dose (90 microg/kg) produced a
      significant excitation in both strains, but this effect remained smaller in the
      mutants. To investigate this difference, we have studied the functional state of
      nAChRs in wild-type and alphaCGRP-/- mice. Both strains exhibited identical
      expression of alpha(7) and alpha(4)beta(2) nAChRs as revealed by
      autoradiographical studies in the VTA. In addition, focal application of
      acetylcholine on DA neurons recorded by patch-clamp revealed identical currents
      mediated by nAChRs in mutant animals, as compared to wild-type mice. These data
      outline the possibility of a contribution of alphaCGRP to the effects of nicotine
      on DA neurons, by a physiological pathway independent of VTA nicotinic receptors.

PMID- 18619949
TI  - Effects of BNST lesions in female rats on forced swimming and navigational
      learning.
AB  - The bed nucleus of the stria terminalis (BNST) in the forebrain shows sexual
      dimorphism in its neuroanatomical connectivity and neurochemical characteristics.
      The structure is involved in many behavioral and motivational phenomena
      particularly related to coping with stress. Female rats differ from males in
      responding to stressful situations such as forced swimming and navigational
      learning in the water maze. It was previously shown that bilateral damage to the
      BNST in male Wistar rats aggravated depression as measured by forced swim tests,
      but did not impair navigational learning in the water maze. The present study
      extended the findings to female rats demonstrating that bilateral electrolytic
      lesions of the BNST increased immobility and decreased climbing compared to sham
      operated controls, but failed to affect performance in the water maze.
      Additionally, lesions did not alter behavior in the open field and the elevated
      plus-maze tests suggesting not only that the modulation of depression by BNST
      lesions is specific, but also providing support for the view that the BNST may
      not necessarily be critically involved in anxiety.

PMID- 18619950
TI  - Inhibition of cell-cycle progression in human colorectal carcinoma Lovo cells by
      andrographolide.
AB  - In recent years, attention has been focused on the anti-cancer properties of pure
      components, an important role in the prevention of disease. Andrographolide
      (Andro), the major constituent of Andrographis paniculata (Burm. F.) Nees plant,
      is implicated towards its pharmacological activity. To investigate the mechanism
      basis for the anti-tumor properties of Andro, Andro was used to examine its
      effect on cell-cycle progression in human colorectal carcinoma Lovo cells. The
      data from cell growth experiment showed that Andro exhibited the anti
      proliferation effect on Lovo cells in a time- and dose-dependent manner. This
      event was accompanied the arrest of the cells at the G1-S phase by Andro at the
      tested concentrations of 0-30 microM. Cellular uptake of Andro and Andro was
      confirmed by capillary electrophoresis analysis and the intracellular
      accumulation of Andro (0.61+/-0.07 microM/mg protein) was observed when treatment
      of Lovo cells with Andro for 12h. In addition, an accumulation of the cells in G1
      phase (15% increase for 10 microM of Andro) was observed as well as by the
      association with a marked decrease in the protein expression of Cyclin A, Cyclin
      D1, Cdk2 and Cdk4. Andro also inducted the content of Cdk inhibitor p21 and p16,
      and the phosphorylation of p53. Further immunoprecipitation studies found that,
      in response to the treatment, the formation of Cyclin D1/Cdk4 and Cyclin A/Cdk2
      complexes had declined, preventing the phosphorylation of Rb and the subsequent
      dissociation of Rb/E2F complex. These results suggested Andro can inhibit Lovo
      cell growth by G1-S phase arrest, and was exerted by inducing the expression of
      p53, p21 and p16 that, in turn, repressed the activity of Cyclin D1/Cdk4 and/or
      Cyclin A/Cdk2, as well as Rb phosphorylation.

PMID- 18619952
TI  - p53 is involved in inducing testicular apoptosis in mice by the altered redox
      status following tertiary butyl hydroperoxide treatment.
AB  - In testis, seminiferous epithelium is one of the most productive self-renewing
      systems in which apoptosis is an important phenomenon. Alteration in the cellular
      redox status has several detrimental effects on the cells, one of which is
      increased rate of apoptotic signals disturbing the natural balance. Since
      apoptotic responses to various therapeutic agents and toxicants follow diverse
      molecular mechanisms, therefore, the present study was designed to explore
      apoptosis in testes under the effect of oxidative stress. Tertiary butyl
      hydroperoxide (tBHP) was used to induce oxidative stress in mice. It was found
      that ROS production in testes by tBHP resulted in increased apoptosis. The
      apoptosis was evident from TUNEL staining in Zenker-fixed paraffin-embedded
      testicular sections of tBHP treated mice testis and DNA fragmentation analysis.
      Increased mRNA and protein expression of p53 in testis were observed by using RT
      PCR and ELISA techniques, respectively. This indicates that p53 expression is
      linked to ROS generation in mice testes. The functional status of p53 was also
      assessed by upregulation of cyclin dependent kinase inhibitor, p21. Thus tBHP
      induced oxidative stress subject testicular cells to apoptosis which seems to
      involve p53.

PMID- 18619951
TI  - In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus
      (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin.
AB  - The lack of a safe and reliable alternative to hormone therapy (HT) for treating
      menopausal symptoms underscores the need for alternative therapies. OBJECTIVE:
      The purpose of this study was to assess the in vivo estrogenic effects of the
      botanical dietary supplements Trifolium pratense (red clover) and Humulus lupulus
      (hops), and two compounds obtained from H. lupulus, isoxanthohumol and 8
      prenylnaringenin (8-PN) using the ovariectomized uterotrophic adult rat model. A
      H. lupulus extract and a 30% isoflavone extract of T. pratense were tested at
      three escalating doses as was one dose of isoxanthohumol for 21d. 8
      Prenylnaringenin, the major estrogen in H. lupulus, was also tested at three
      relevant escalating doses. In order to determine the in vivo metabolism of 8-PN,
      the major phases I and II metabolites were also identified. The primary outcome
      measure, uterus weight gain, indicated that H. lupulus and T. pratense did not
      have an estrogenic effect on the uterus, and none of the secondary outcome
      measures were positive. In contrast, there was a clear dose response when 8-PN
      was evaluated where the middle and high doses of 8-PN were active. 8
      Prenylnaringenin in rat plasma, liver, and mammary gland was measured and the
      major phases I and II 8-PN metabolites were detected. Our findings suggest that
      while both the H. lupulus and T. pratense extracts do not have an effect on the
      rat uterus, 8-PN at equivalent doses to those previously used in humans did have
      an effect, and may therefore have a deleterious effect in women.

PMID- 18619953
TI  - How reliable an indicator of inflammation is myeloperoxidase activity?
AB  - BACKGROUND: Myeloperoxidase (MPO) and interleukin-6 (IL-6) are often used as
      markers of inflammation. The aim of this study was to ascertain whether MPO
      activity is as reliable as IL-6 as an indicator of inflammation. METHODS:
      Inflammation was induced in mice, using either turpentine or indomethacin.
      Duodenal tissue was removed from these animals at various time periods ranging
      from 6 h to 7 days later. Concentrations of IL-6 and MPO activity were estimated
      in the tissue. Histopathological examination was also carried out at some of the
      time periods to determine the presence of neutrophil infiltration in turpentine
      treated mice. RESULTS: Concentrations of IL-6 and MPO activity were significantly
      higher in tissue that had been treated with the agents used, at all the time
      periods studied, when compared with corresponding control tissue. Fold-increases
      in MPO activity were higher than fold-increases in IL-6. Concentrations of the 2
      parameters showed significant positive correlation. Histopathological examination
      did not show significantly higher numbers of neutrophils infiltrating the tissue
      in response to turpentine, at the time periods studied. CONCLUSIONS: Estimation
      of MPO activity is a reliable indicator of inflammation, being more sensitive
      than histopathological examination of tissue and as good as measurement of IL-6
      concentrations.

PMID- 18619954
TI  - Specific requirements of MRFs for the expression of muscle specific microRNAs,
      miR-1, miR-206 and miR-133.
AB  - The expression of three microRNAs, miR-1, miR-206 and miR-133 is restricted to
      skeletal myoblasts and cardiac tissue during embryo development and muscle cell
      differentiation, which suggests a regulation by muscle regulatory factors (MRFs).
      Here we show that inhibition of C2C12 muscle cell differentiation by FGFs, which
      interferes with the activity of MRFs, suppressed the expression of miR-1, miR-206
      and miR-133. To further investigate the role of myogenic regulators (MRFs), Myf5,
      MyoD, Myogenin and MRF4 in the regulation of muscle specific microRNAs we
      performed gain and loss-of-function experiments in vivo, in chicken and mouse
      embryos. We found that directed expression of MRFs in the neural tube of chicken
      embryos induced ectopic expression of miR-1 and miR-206. Conversely, the lack of
      Myf5 but not of MyoD resulted in a loss of miR-1 and miR-206 expression. Taken
      together our results demonstrate differential requirements of distinct MRFs for
      the induction of microRNA gene expression during skeletal myogenesis.

PMID- 18619955
TI  - Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1).
AB  - The ATP-binding cassette (ABC) transporter ABCC1, or multidrug resistance-related
      protein 1 (MRP1) is implicated in Phase II metabolism and multidrug resistance as
      it effluxes substrate anticancer drugs. As cannabinoids inhibit two related ABC
      transporters, P-glycoprotein and ABCG2, here we examined whether they also
      inhibit ABCC1. Indeed, the cannabinoids enhanced the intracellular accumulation
      of two ABCC1 substrates, Fluo3 and vincristine, in ovarian carcinoma cells over
      expressing ABCC1 (2008/MRP1) with a rank order of potency:
      cannabidiol>cannabinol>Delta(9)-tetrahydrocannabinol. Cannabinoid inhibition of
      ABCC1 was confirmed using insect cell membrane MRP1 ATPase assays. These results
      demonstrate that cannabinoids inhibit ABCC1.

PMID- 18619956
TI  - Effect of 17alpha-ethinyl estradiol on active phase rapid eye movement sleep
      microarchitecture.
AB  - Estrogen treatment decreases active phase rapid eye movement (REM) sleep in
      ovariectomized rats. Here we explored further the effect of 17alpha-ethinyl
      estradiol (17alpha-EE) on active phase REM sleep in ovariectomized rats by
      analyzing spectral properties and the number and length of REM sleep bouts. The
      greatest suppression of REM sleep occurred on day 4 of 17alpha-EE treatment, was
      due to decreases in bout length, and was accompanied by decreased EEG theta
      power. These results further elucidate 17alpha-EE's effects on REM sleep and
      provide greater understanding of the mechanisms by which estrogens alter sleep
      wakefulness patterns.

PMID- 18619957
TI  - Statins suppress MMP2 secretion via inactivation of RhoA/ROCK pathway in
      pulmonary vascular smooth muscles cells.
AB  - Recent studies have shown that statins ameliorate hypoxia-induced pulmonary
      hypertension in animal models. Yet, the underlying molecular mechanisms have not
      been completely understood. Here, we investigated the hypothesis that statins
      regulate vascular remodeling by modulation of matrix metalloproteinases (MMP)
      secretion in primary cultured pulmonary artery smooth muscle cells (PASMCs).
      Angiotensin II induced a concentration-dependent MMP2 secretion. A 2.75 fold
      increase was achieved by 100 nM angiotensin II stimulation for 24 h in primary
      cultured PASMCs (P<0.01 versus control), which was reversed by silencing Ras
      homolog gene family member A (RhoA) or inhibition of its downstream Rho
      associated kinase (ROCK). There was no effect of angiotensin II on the expression
      of tissue inhibitors of matrix metalloproteinases (TIMPs). Pre-exposure of cells
      to simvastatin concentration-dependently blocked angiotensin II-stimulated MMP2
      release. MMP2 release was reduced to1.34 fold increase in the presence of 10
      microM simvastatin (P<0.01 versus angiotensin II-stimulated cells). We further
      revealed that simvastatin suppression of RhoA activation mediated its inhibitory
      effect on angiotensin II-triggered MMP2 release. Similarly, simvastatin
      suppressed endothelin-1-induced MMP2 release through RhoA/ROCK pathway. These
      results indicated a novel statins-regulation of RhoA/ROCK signaling against
      pulmonary vascular remodeling, and suggest that statins could prove useful in
      targeting this pathway in pulmonary hypertension and other disease conditions.

PMID- 18619958
TI  - Calebin-A induces apoptosis and modulates MAPK family activity in drug resistant
      human gastric cancer cells.
AB  - This study is the first to investigate Calebin-A, a natural compound present in
      Curcuma longa, which inhibits cell growth and induce apoptosis in
      SGC7901/VINCRISTINE cells, a multidrug resistant (MDR) human gastric
      adenocarcinoma cell line. Our data suggest the drug efflux function of P
      glycoprotein was inhibited by Calebin-A treatment, while the expression level of
      P-glycoprotein was not affected. Additionally, co-treatment of Calebin-A and
      vincristine resulted in a remarkable reduction in S phase and G2/M phase arrest
      in SGC7901/VINCRISTINE cells. Calebin-A was also found to modulate the activities
      of mitogen-activated protein kinase (MAPK) family members, which includes
      decreased c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase
      (ERK) and increased protein kinase of 38 kDa (p38) activity. These results
      suggest that Calebin-A might be an effective compound for the treatment of human
      gastric and other MDR cancers.

PMID- 18619959
TI  - Expression of p63 and p73 in retinoblastoma: a clinicopathological correlation
      study.
AB  - The aim of the study was to explore the expression profile of p63, p73 and their
      delta isoforms in the retinoblastoma tumor samples and to correlate with
      clinicopathological parameters. Immunohistochemistry was performed for p63, delta
      p63, p73 and delta p73 on the archival paraffin sections of retinoblastoma and
      correlated with clinicopathological features. Western blotting was performed to
      confirm immunoreactivity results. p63 immunoreactivity was observed in 59%
      (29/49) of the RB specimens. p63 was expressed in 60% (20/33) low risk tumors and
      in 56% (9/16) of high risk tumors. p73 was expressed in 77% (38/49) RB specimens.
      Among the 33 low risk tumors, p73 was expressed in 69% (23/33) tumors and among
      the 26 high risk tumors, p73 was expressed in 93% (15/16) tumors. High risk
      tumors showed significantly increased expression of p73 compared to tumors with
      low risk (P<0.05). This is the first correlation between p63/p73 expression and
      histopathology in human RB tumors. Our study showed increased expression of p73
      in high risk tumors (P<0.05) compared to low risk tumors. Further functional
      studies are required to explore the role of p63, p73 and their respective
      isoforms in retinoblastoma.

PMID- 18619961
TI  - Ammonium-dependent hydrogen peroxide production by mitochondria.
AB  - NADH-supported generation of H2O2 by permeabilized rat heart mitochondria was
      partially prevented by the specific complex I-directed inhibitor, NADH-OH, and
      was significantly stimulated by ammonium. Ammonium did not affect H2O2 production
      by complex I in coupled submitochondrial particles. The soluble mitochondrial
      matrix protein fraction catalyzed NADH-dependent H2O2 production, which was
      greatly (approximately 10-fold) stimulated by ammonium. We conclude that complex
      I is not the major contributor to mitochondrial superoxide (hydrogen peroxide)
      generation and that there are specific ammonium-sensitive NADH:oxygen
      oxidoreductase(s) in the mitochondrial matrix which are responsible for
      mitochondrial H2O2 production.

PMID- 18619960
TI  - Endogenous small RNAs and antibacterial immunity in plants.
AB  - Small RNAs are non-coding regulatory RNA molecules that control gene expression
      by mediating mRNA degradation, translational inhibition, or chromatin
      modification. Virus-derived small RNAs induce silencing of viral RNAs and are
      essential for antiviral defense in both animal and plant systems. The role of
      host endogenous small RNAs on antibacterial immunity has only recently been
      recognized. Host disease resistance and defense responses are achieved by
      activation and repression of a large array of genes. Certain endogenous small
      RNAs in plants, including microRNAs (miRNAs) and small interfering RNAs (siRNAs),
      are induced or repressed in response to pathogen attack and subsequently regulate
      the expression of genes involved in disease resistance and defense responses by
      mediating transcriptional or post-transcriptional gene silencing. Thus, these
      small RNAs play an important role in gene expression reprogramming in plant
      disease resistance and defense responses. This review focuses on the recent
      findings of plant endogenous small RNAs in antibacterial immunity.

PMID- 18619962
TI  - A novel interaction between the proto-oncogene Evi1 and histone
      methyltransferases, SUV39H1 and G9a.
AB  - The transcription factor ecotropic viral integration site 1 (Evi1) is associated
      with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients
      due to chromosomal aberration of chromosome 3. Here we show that Evi1 interacts
      with the histone methyltransferase SUV39H1. The interaction requires the N
      terminal part of Evi1 and the H3-specific histone methyltransferase domain, SET,
      of SUV39H1 without Evi1 having an inhibitory effect on SUV39H1 methyltransferase
      activity. Presence of SUV39H1 enhances Evi1 transcriptional repression in a dose
      dependent manner. In addition, Evi1 also interacts with another histone
      methyltransferase, G9a, but not with SET9. Our data establish an epigenetic role
      of Evi1 in cell transformation by recruiting higher order chromatin remodeling
      complexes.

PMID- 18619963
TI  - DNA-binding profiling of human hormone nuclear receptors via fluorescence
      correlation spectroscopy in a cell-free system.
AB  - The nuclear hormone receptors (NHRs), a family of transcription factors, bind
      directly to the hormone response elements (HREs) to regulate gene expression. In
      this study, we describe a comprehensive NHR-HRE profiling analysis with a new
      high-throughput DNA binding assay system utilizing wheat germ cell-free protein
      production and fluorescence correlation spectroscopy (FCS). This approach
      revealed NHR binding to natural response elements and new heterodimeric NHR-HRE
      bindings. We analyzed 408 possible binding combinations between 34 human NHRs and
      12 different HREs, and identified 205 NHR-HRE binding combinations, 124 of which
      have not been previously reported. Thus, this study provides a novel biochemical
      classification of the human NHRs, as well as describing a novel approach to the
      large-scale analysis of DNA-protein interactions.

PMID- 18619964
TI  - Heat shock protein 60 induces inflammatory mediators in mouse adipocytes.
AB  - Adipocytes represent an important cellular source of inflammatory mediators.
      However, the signals for the induction of proinflammatory adipocyte activities
      are largely unknown. Here, we demonstrate that heat shock protein (Hsp) 60, a
      potent stimulator of innate immunity, induces the release of the inflammatory
      mediators interleukin-6, CXCL1 and monocyte chemoattractant protein-1 in a time-
      and concentration-dependent manner from cells of the adipocyte line 3T3-L1 and
      from adipocytes of obese mice. These results identify Hsp60 as an important
      regulator of adipocyte functions which contribute to the development of
      inflammatory processes as observed in diabetes and diabetes-associated
      complications.

PMID- 18619965
TI  - Syndecan-4 regulates platelet-derived growth factor-mediated MAP kinase
      activation by altering intracellular reactive oxygen species.
AB  - The cell adhesion receptor, syndecan-4, regulates cellular interactions with both
      the extracellular matrix and soluble ligands. Accumulating evidence also suggests
      that cell adhesion is involved in generating reactive oxygen species (ROS). Here,
      we investigated the role of syndecan-4 in regulating growth factor-induced ROS
      generation. Rat embryo fibroblasts (REFs) overexpressing syndecan-4 exhibited
      increased ROS levels compared to control cells. Expression of the non-phagocytic
      NADH oxidase component Nox1 was increased in syndecan-4-overexpressing REFs and
      syndecan-4-mediated ROS generation was diminished when levels of Nox1 were
      knocked-down with small inhibitory RNAs. In addition, syndecan-4 enhanced
      platelet-derived growth factor (PDGF)-induced MAP kinase activity in parallel
      with ROS generation. Collectively, these data suggest that syndecan-4 regulates
      PDGF-induced MAP kinase activation by altering ROS generation.

PMID- 18619966
TI  - The gastroenterology fellowship match--the first two years.

PMID- 18619968
TI  - Guardians of the gut: newly appreciated role of epithelial toll-like receptors in
      protecting the intestine.

PMID- 18619969
TI  - Electronic clinical challenges and images in GI. Lymphomatous polyposis.

PMID- 18619970
TI  - Hedgehog spikes pancreas regeneration.

PMID- 18619971
TI  - Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in
      noninfected volunteers: a phase I study.
AB  - INTRODUCTION: Helicobacter pylori infection is among the most common human
      infections and the major risk factor for peptic disease and gastric cancer.
      Immunization with vaccines containing the H pylori vacuolating cytotoxin A
      (VacA), cytotoxin-associated antigen (CagA), and neutrophil-activating protein
      (NAP), alone or in combination, have been shown to prevent experimental infection
      in animals. AIM: We sought to study the safety and immunogenicity of a vaccine
      consisting of recombinant VacA, CagA, and NAP given intramuscularly with
      aluminium hydroxide as an adjuvant to noninfected healthy subjects. METHODS: This
      controlled, single-blind Phase I study randomized 57 H pylori-negative volunteers
      into 7 study arms exploring 2 dosages (10 and 25 microg) of each antigen and 3
      schedules (0, 1, 2 weeks; 0, 1, 2 months; and 0, 1, 4 months) versus alum
      controls. All participants were followed for 5 months. Thirty-six subjects
      received a booster vaccination 18-24 months after the completion of the primary
      vaccination. RESULTS: Local and systemic adverse reactions were mild and similar
      in placebo and vaccine recipients on the monthly schedules. All subjects
      responded to 1 or 2 of the antigens and 86% of all vaccines mounted
      immunoglobulin G antibody responses to all 3 antigens. Vaccinees exhibited an
      antigen-specific cellular response. Vaccination 18-24 months later elicited
      anamnestic antibody and cellular responses. CONCLUSIONS: This intramuscular H
      pylori vaccine demonstrated satisfactory safety and immunogenicity, produced
      antigen-specific T-cell memory, and, therefore, warrants further clinical study.

PMID- 18619972
TI  - CCL3 (MIP-1 alpha) levels are elevated during acute coronary syndromes and show
      strong prognostic power for future ischemic events.
AB  - As chemokines are considered instrumental in thrombotic plaque rupture and
      erosion as well as in ischemia-reperfusion injury processes, we aimed to identify
      previously unknown chemokines associated with acute coronary syndromes. Plasma of
      44 patients with acute myocardial infarction (AMI) and 22 controls were profiled
      for a panel of chemokines by multiplex analysis. Levels of CCL3 were
      prospectively verified in 54 patients with unstable angina pectoris (UAP). An AMI
      mouse model was used to assess the relationship between differentially expressed
      chemokines and myocardial ischemia. CCL3 levels were significantly elevated in
      AMI vs. controls (P=0.02) albeit, that adjustment for confounding factors
      attenuated this association. In support of a direct association with cardiac
      ischemia CCL3 levels were also seen to be elevated in patients with UAP at
      baseline and significantly down-regulated after 180 days (P<0.001). Importantly,
      baseline upper quartile levels were strongly correlated with future acute
      coronary syndromes (Likelihood Ratio 11.5; P<0.01). Furthermore circulating
      levels of CCL3 were significantly enhanced after AMI in mice (P=0.02), while
      CCR5(+) T-cell numbers were increased as well, suggestive of CCL3 driven T-cell
      homing towards the ischemic area. CCL3 levels are elevated during ACS and
      released upon ischemia. Since CCL3 specifically predicts future cardiovascular
      events, it may serve as a predictive biomarker.

PMID- 18619973
TI  - High glucose reduces cathepsin L activity and impairs invasion of circulating
      progenitor cells.
AB  - Endothelial progenitor cells (EPC) significantly contribute to neovascularization
      and endothelial regeneration. Risk factors for coronary artery disease,
      particularly diabetes mellitus, reduce the number and functional activity of EPC.
      As we have recently shown, expression and activity of the matrix degrading
      cysteine protease cathepsin L in EPC is required for tissue invasion and EPC
      mediated improvement of neovascularization. Therefore, we investigated the effect
      of high glucose and diabetes mellitus on EPC invasion and cathepsin L activity.
      Incubation of EPC with high levels of glucose (10-30 mM) dose-dependently
      decreased cathepsin L activity (glucose 20 mM: 67+/-4% compared to control;
      p<0.05) and protein expression (48+/-5% of control, p<0.05). In contrast, other
      proteases of the cathepsin family such as cathepsins D and O, and the matrix
      metalloproteinases MMP-2 and MMP-9 were not altered with high glucose. Cathepsin
      L mRNA was not affected suggesting that a posttranscriptional mechanism is
      responsible for cathepsin L down-regulation. As a functional consequence, high
      glucose significantly reduced the gelatinolytic activity and invasion of EPC
      (50+/-5% of control). Importantly, EPC of patients with type 2 diabetes revealed
      profoundly decreased cathepsin L expression and activity as compared to EPC
      derived from healthy controls. Taken together, high glucose significantly reduces
      the protein expression and activity of cathepsin L, which is involved in matrix
      degradation and required for invasion of EPC into the ischemic tissue, and,
      thereby, may limit the functional capacity of EPC to improve neovascularization
      in diabetics.

PMID- 18619974
TI  - Combinatorial optimization of a CD4-mimetic miniprotein and cocrystal structures
      with HIV-1 gp120 envelope glycoprotein.
AB  - Miniproteins provide a bridge between proteins and small molecules. Here we adapt
      methods from combinatorial chemistry to optimize CD4M33, a synthetic miniprotein
      into which we had previously transplanted the HIV-1 gp120 binding surface of the
      CD4 receptor. Iterative deconvolution of generated libraries produced CD4M47, a
      derivative of CD4M33 that had been optimized at four positions. Surface plasmon
      resonance demonstrated fourfold to sixfold improvement in CD4M47 affinity for
      gp120 to a level about threefold tighter than that of CD4 itself. Assessment of
      the neutralization properties of CD4M47 against a diverse range of isolates
      spanning from HIV-1 to SIVcpz showed that CD4M47 retained the extraordinary
      breadth of the parent CD4M33, but yielded only limited improvements in
      neutralization potencies. Crystal structures of CD4M47 and a phenylalanine
      variant ([Phe23]M47) were determined at resolutions of 2.4 and 2.6 A, in ternary
      complexes with HIV-1 gp120 and the 17b antibody. Analysis of these structures
      revealed a correlation between mimetic affinity for gp120 and overall mimetic
      gp120 interactive surface. A correlation was also observed between CD4- and
      mimetic-induced gp120 structural similarity and CD4- and mimetic-induced gp120
      affinity for the CCR5 coreceptor. Despite mimetic substitutions, including a
      glycine-to-(d)-proline change, the gp120 conformation induced by CD4M47 was as
      close or closer to the conformation induced by CD4 as the one induced by the
      parent CD4M33. Our results demonstrate the ability of combinatorial chemistry to
      optimize a disulfide-containing miniprotein, and of structural biology to
      decipher the resultant interplay between binding affinity, neutralization
      breadth, molecular mimicry, and induced affinity for CCR5.

PMID- 18619975
TI  - Extensive conformational transitions are required to turn on ATP hydrolysis in
      myosin.
AB  - Conventional myosin is representative of biomolecular motors in which the
      hydrolysis of adenosine triphosphate (ATP) is coupled to large-scale structural
      transitions both in and remote from the active site. The mechanism that underlies
      such "mechanochemical coupling," especially the causal relationship between
      hydrolysis and allosteric structural changes, has remained elusive despite
      extensive experimental and computational analyses. In this study, using combined
      quantum mechanical and molecular mechanical simulations and different
      conformations of the myosin motor domain, we provide evidence to support that
      regulation of ATP hydrolysis activity is not limited to residues in the immediate
      environment of the phosphate. Specifically, we illustrate that efficient
      hydrolysis of ATP depends not only on the proper orientation of the lytic water
      but also on the structural stability of several nearby residues, especially the
      Arg238-Glu459 salt bridge (the numbering of residues follows myosin II in
      Dictyostelium discoideum) and the water molecule that spans this salt bridge and
      the lytic water. More importantly, by comparing the hydrolysis activities in two
      motor conformations with very similar active-site (i.e., Switches I and II)
      configurations, which distinguished this work from our previous study, the
      results clearly indicate that the ability of these residues to perform crucial
      electrostatic stabilization relies on the configuration of residues in the nearby
      N-terminus of the relay helix and the "wedge loop." Without the structural
      support from those motifs, residues in a closed active site in the post-rigor
      motor domain undergo subtle structural variations that lead to consistently
      higher calculated ATP hydrolysis barriers than in the pre-powerstroke state. In
      other words, starting from the post-rigor state, turning on the ATPase activity
      requires not only displacement of Switch II to close the active site but also
      structural transitions in the N-terminus of the relay helix and the "wedge loop,"
      which have been proposed previously to be ultimately coupled to the rotation of
      the converter subdomain 40 A away.

PMID- 18619976
TI  - Force-based analysis of multidimensional energy landscapes: application of
      dynamic force spectroscopy and steered molecular dynamics simulations to an
      antibody fragment-peptide complex.
AB  - Multidimensional energy landscapes are an intrinsic property of proteins and
      define their dynamic behavior as well as their response to external stimuli. In
      order to explore the energy landscape and its implications on the dynamic
      function of proteins dynamic force spectroscopy and steered molecular dynamics
      (SMD) simulations have proved to be important tools. In this study, these
      techniques have been employed to analyze the influence of the direction of the
      probing forces on the complex of an antibody fragment with its peptide antigen.
      Using an atomic force microscope, experiments were performed where the attachment
      points of the 12 amino acid long peptide antigen were varied. These measurements
      yielded clearly distinguishable basal dissociation rates and potential widths,
      proving that the direction of the applied force determines the unbinding pathway.
      Complementary atomistic SMD simulations were performed, which also show that the
      unbinding pathways of the system are dependent on the pulling direction. However,
      the main barrier to be crossed was independent of the pulling direction and is
      represented by a backbone hydrogen bond between Gly(H)-H40 of the antibody
      fragment and Glu(Oepsilon)-6(peptide) of the peptide. For each pulling direction,
      the observed barriers can be correlated with the rupture of specific
      interactions, which stabilize the bound complex. Furthermore, although the SMD
      simulations were performed at loading rates exceeding the experimental rates by
      orders of magnitude due to computational limitations, a detailed comparison of
      the barriers that were overcome in the SMD simulations with the data obtained
      from the atomic force microscope unbinding experiments show excellent agreement.

PMID- 18619977
TI  - Ribosome collisions and translation efficiency: optimization by codon usage and
      mRNA destabilization.
AB  - Individual mRNAs are translated by multiple ribosomes that initiate translation
      with an interval of a few seconds. The ribosome speed is codon dependent, and
      ribosome queuing has been suggested to explain specific data for translation of
      some mRNAs in vivo. By modeling the stochastic translation process as a traffic
      problem, we here analyze conditions and consequences of collisions and queuing.
      The model allowed us to determine the on-rate (0.8 to 1.1 initiations/s) and the
      time (1 s) the preceding ribosome occludes initiation for Escherichia coli lacZ
      mRNA in vivo. We find that ribosome collisions and queues are inevitable
      consequences of a stochastic translation mechanism that reduce the translation
      efficiency substantially on natural mRNAs. The cells minimize collisions by
      having its mRNAs being unstable and by a highly selected codon usage in the start
      of the mRNA. The cost of mRNA breakdown is offset by the concomitant increase in
      translation efficiency.

PMID- 18619978
TI  - Diffusional constraints on energy metabolism in skeletal muscle.
AB  - Aerobic metabolic flux depends on the diffusion of high-energy phosphate
      molecules (e.g., ATP and phosphocreatine) from the mitochondria to cellular
      ATPases, as well as the diffusion of other molecules (e.g., ADP, Pi) back to the
      mitochondria. Here, we develop an approach for evaluating the influence of
      intracellular metabolite diffusion on skeletal muscle aerobic metabolism through
      the application of the effectiveness factor (eta). This parameter provides an
      intuitive and informative means of quantifying the extent to which diffusion
      limits metabolic flux. We start with the classical approach assuming an infinite
      supply of substrate at the fiber boundary, and we expand this model to ultimately
      include nonlinear boundary and homogeneous reactions. Comparison of the model
      with experimental data from a wide range of skeletal muscle types reveals that
      most muscle fibers are not substantially limited by diffusion (eta close to
      unity), but many are on the brink of rather substantial diffusion limitation.
      This implies that intracellular metabolite diffusion does not dramatically limit
      aerobic metabolic flux in most fibers, but it likely plays a role in limiting the
      evolution of muscle fiber design and function.

PMID- 18619979
TI  - Cyanidin-3-O-beta-glucoside inhibits iNOS and COX-2 expression by inducing liver
      X receptor alpha activation in THP-1 macrophages.
AB  - Anthocyanins belong to a large and widespread group of water-soluble
      phytochemicals and exhibit potent antioxidative and anti-inflammatory properties;
      however, the molecular mechanisms of these biochemical actions mediated by
      anthocyanins remain unclear. In this study, our data show that pretreatment of
      THP-1 macrophages with Cyanidin-3-O-beta-glucoside (C3G) for 12 h can enhance the
      expression and transcriptional activities of the nuclear receptor peroxisome
      proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha
      (LXRalpha). Furthermore, pretreatment of these cells with C3G for 12 h causes
      dose-dependent inhibition of lipopolysaccharide (LPS)-induced nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the mRNA and protein levels
      together with a decrease in nitric oxide (NO) and prostaglandin E(2) (PGE(2))
      production. Consequently, addition of geranylgeranyl pyrophosphate ammonium salt
      (GGPP), an LXRalpha antagonist, significantly downregulates the inhibitory effect
      of C3G on LPS-induced iNOS and COX-2 expression in THP-1 macrophages, whereas the
      PPARgamma antagonist GW9662 has no effect. Further investigation revealed that
      LXRalpha might interfere with LPS-induced iNOS and COX-2 expression by
      suppressing the functional activation of nuclear factor-kappaB (NF-kappaB), not -
      as was previously proposed - by reducing NF-kappaB nuclear translocation. Taken
      together, these results indicate that LXRalpha activation has an essential role
      in the anti-inflammatory property of C3G. Moreover, they provide new insight into
      the molecular basis for the anti-inflammatory property of anthocyanins.

PMID- 18619980
TI  - Pre-clinical evidence for altered absorption and biliary excretion of irinotecan
      (CPT-11) in combination with quercetin: possible contribution of P-glycoprotein.
AB  - P-glycoprotein (P-gp) is found to play a very significant role in intestinal and
      biliary transport of irinotecan and its active metabolite, SN-38. This makes P-gp
      inhibition a logical strategy for improving irinotecan's oral efficacy and
      reducing its toxicity. The objective of the present study was to identify the
      most suitable P-gp inhibitor, amongst various commonly used herbal components via
      in vitro screening; followed by determination of in vivo effects in rats. Caco-2
      cell monolayers were used to investigate the influence of various components
      (quercetin, hesperitin, piperine, curcumin and naringenin) on the transport of
      irinotecan. The secretory transport (basolateral-to-apical) was significantly
      decreased by all components (p<0.05) except piperine. In the apical-to
      basolateral transport, quercetin showed the highest absorptive permeability
      enhancement and P-gp interaction potential making it an appropriate candidate for
      further in vivo studies in female Wistar rats. Quercetin pre-treatment resulted
      in increased irinotecan C(max) and area under curve (AUC) with a concomitant
      decrease in t(max), plasma clearance and volume of distribution (p<0.05). The
      absolute bioavailability (F) of irinotecan control was 33%, which was increased
      to 43% (1.3 fold) by quercetin administration. The amounts of irinotecan and SN
      38 eliminated in bile in control rats, is reduced to almost half when treated
      with quercetin. Our studies not only propose a safe approach for bioavailability
      enhancement and reducing toxicity of irinotecan by P-gp inhibition but in another
      way also reiterate the significance of elucidating herb-drug interactions for
      future insights.

PMID- 18619981
TI  - Influence of various radiographic contrast media on the buckling of endothelial
      cells.
AB  - The intra-arterial application of radiographic contrast media (RCM) can induce
      decreases of blood flow velocity in downstream capillaries as well as a decrease
      in the tissue oxygen tension. It is unclear whether changes in endothelial cell
      morphology contribute to the observed microcirculatory disorders. Four RCMs
      (Iodixanol320, Iohexol350, Iopromide370, and Imeron350) were added to the culture
      medium of human umbilical venous endothelial cells (HUVEC) and used for short
      term incubation studies of these cells. Addition of Iohexol (p=0.6377) and
      Iodixanol (p=0.6309) did not affect the HUVEC height 1.5 min after incubation in
      the modified cell culture media supplemented with 30% v/v of the respective RCM.
      Strong buckling and increased endothelial height appeared after incubation in
      Iopromide-supplemented medium (the cell height increased by 95% compared to cells
      incubated under control conditions; p=0.0065). Addition of Iomeprol-supplemented
      medium caused an increase by 61.6% compared to cells incubated under control
      conditions; p=0.0051. After 5 min of incubation in any of the RCM-supplemented
      media, there was no difference in HUVEC height in comparison to incubation in
      control standard culture media (each p value>0.05). The tremendous buckling
      caused by Iopromide and Iomeprol, coinciding with an echinocyte formation of
      erythrocytes might be the reason why a bolus injection of Iopromide in vivo into
      the left coronary artery was followed by a 50% decrease of oxygen partial
      pressure in the supplied tissue.

PMID- 18619982
TI  - Dual neurotoxic and neuroprotective role of metabotropic glutamate receptor 1 in
      conditions of trophic deprivation - possible role as a dependence receptor.
AB  - Group I metabotropic glutamate receptors have been often implicated in various
      models of neuronal toxicity, however, the role played by the individual receptors
      and their putative mechanisms of action contributing to neurotoxicity or
      neuroprotection remain unclear. Here, using primary cultures of rat cerebellar
      granule cells and mouse cortical neurons, we show that conditions of trophic
      deprivation increased mGlu1 expression which correlated with the developing cell
      death. The inhibition of mGlu1 expression by specific siRNA attenuated toxicity,
      while adenovirus-mediated overexpression of mGlu1 resulted in increased cell
      death, indicating a causal relationship between the level of receptor expression
      and neuronal survival. In pharmacological experiments selective mGlu1 antagonists
      failed to protect from mGlu1-induced cell death, instead, neuronal survival was
      promoted by glutamate acting at mGlu1 receptors. Such properties are
      characteristics of a novel heterogeneous family of dependence receptors which
      control neuronal apoptosis. Our findings indicate that increased expression of
      mGlu1 in neurons creates a state of cellular dependence on the presence of its
      endogenous agonist glutamate. We propose a new role and a new mechanism for mGlu1
      action. This receptor may play a crucial role in determining the fate of
      individual neurons during the development of the nervous system.

PMID- 18619983
TI  - Switch in the expression of mGlu1 and mGlu5 metabotropic glutamate receptors in
      the cerebellum of mice developing experimental autoimmune encephalomyelitis and
      in autoptic cerebellar samples from patients with multiple sclerosis.
AB  - Recent evidence suggests that changes in the expression of membrane receptors/ion
      channels in cerebellar Purkinje cells contribute to the onset of cerebellar motor
      symptoms in patients with multiple sclerosis (MS). We examined the expression of
      group-I metabotropic glutamate receptors (mGlu1 and mGlu5 receptors) in the
      cerebellum of mice developing experimental autoimmune encephalomyelitis (EAE) and
      in autoptic cerebellar samples of MS patients. EAE was induced in mice by
      immunization with the 35-55 fragment of MOG (myelin oligodendrocyte
      glycoprotein). EAE mice showed a progressive loss of mGlu1a receptors in the
      cerebellum, associated with an increased expression of mGlu5 receptors. These
      changes were restricted to Purkinje cells and their dendritic arborization, as
      shown by immunohistochemistry. A reduced expression of mGlu1a receptors in
      cerebellar Purkinje cells was also found in 7 of 9 MS patients. In addition, a
      light/moderate to very strong mGlu5 receptor immunoreactivity was detected in
      Purkinje cells of 8 MS patients, but was always absent in non-MS control
      patients. In EAE mice, an acute treatment with the mGlu1 receptor enhancer, 9H
      xanthene-9-carboxylic acid (4-trifluoromethyl-oxazol-2-yl)-amide (RO0711401),
      significantly improved motor coordination, whereas treatment with the mGlu5
      receptor antagonists, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and 6-methyl-2
      (phenylazo)-3-pyridinol (SIB-1757), had no effect. We conclude that mGlu1
      receptor enhancers improve motor symptoms associated with EAE and might be
      helpful as symptomatic drugs in patients with MS.

PMID- 18619985
TI  - A case of persistent retrograde amnesia following a dissociative fugue:
      neuropsychological and neurofunctional underpinnings of loss of autobiographical
      memory and self-awareness.
AB  - Autobiographical memory relies on complex interactions between episodic memory
      contents, associated emotions and a sense of self-continuity over the course of
      one's life. This paper reports a study based upon the case of the patient NN who
      suffered from a complete loss of autobiographical memory and awareness of
      identity subsequent to a dissociative fugue. Neuropsychological, behavioral, and
      functional neuroimaging tests converged on the conclusion that NN suffered from a
      selective retrograde amnesia following an episode of dissociative fugue, during
      which he had lost explicit knowledge and vivid memory of his personal past. NN's
      loss of self-related memories was mirrored in neurobiological changes after the
      fugue whereas his semantic memory remained intact. Although NN still claimed to
      suffer from a stable loss of autobiographical, self-relevant memories 1 year
      after the fugue state, a proportionate improvement in underlying fronto-temporal
      neuronal networks was evident at this point in time. In spite of this improvement
      in neuronal activation, his anterograde visual memory had been decreased. It is
      posited that our data provide evidence for the important role of visual
      processing in autobiographical memory as well as for the efficiency of protective
      control mechanisms that constitute functional retrograde amnesia.

PMID- 18619984
TI  - Cue-induced reinstatement of alcohol-seeking behavior is associated with
      increased ERK1/2 phosphorylation in specific limbic brain regions: blockade by
      the mGluR5 antagonist MPEP.
AB  - Relapse to alcohol use after periods of abstinence is a hallmark behavioral
      pathology of alcoholism and a major clinical problem. Emerging evidence indicates
      that metabotropic glutamate receptor 5 (mGluR5) antagonists attenuate relapse to
      alcohol-seeking behavior but the molecular mechanisms of this potential
      therapeutic effect remain unexplored. The extracellular signal-regulated kinase
      (ERK1/2) pathway is downstream of mGluR5 and has been implicated in addiction. We
      sought to determine if cue-induced reinstatement of alcohol-seeking behavior, and
      its reduction by an mGluR5 antagonist, is associated with changes in ERK1/2
      activation in reward-related limbic brain regions. Selectively-bred alcohol
      preferring (P) rats were trained to lever press on a concurrent schedule of
      alcohol (15% v/v) vs. water reinforcement. Following 9 days of extinction, rats
      were given an additional extinction trial or injected with the mGluR5 antagonist
      MPEP (0, 1, 3, or 10mg/kg) and tested for cue-induced reinstatement. Brains were
      removed 90-min later from the rats in the extinction and MPEP (0 or 10mg/kg)
      conditions for analysis of p-ERK1/2, total ERK1/2, and p-ERK5 immunoreactivity
      (IR). Cue-induced reinstatement of alcohol-seeking behavior was associated with a
      three to five-fold increase in p-ERK1/2 IR in the basolateral amygdala and
      nucleus accumbens shell. MPEP administration blocked both the relapse-like
      behavior and increase in p-ERK1/2 IR. p-ERK1/2 IR in the central amygdala and
      NAcb core was dissociated with the relapse-like behavior and the pharmacological
      effect of mGluR5 blockade. No changes in total ERK or p-ERK5 were observed. These
      results suggest that exposure to cues previously associated with alcohol self
      administration is sufficient to produce concomitant increases in relapse-like
      behavior and ERK1/2 activation in specific limbic brain regions. Pharmacological
      compounds, such as mGluR5 antagonists, that reduce cue-induced ERK1/2 activation
      may be useful for treatment of relapse in alcoholics that is triggered by
      exposure to environmental events.

PMID- 18619986
TI  - Effects of endogenous hydrogen peroxide and glutathione on the stability of
      arsenic metabolites in rat bile.
AB  - Trivalent arsenicals such as arsenite (iAs(III)), monomethylarsonous acid
      (MMA(III)) and dimethylarsinous acid (DMA(III)) are more toxic than analogous
      pentavalent compounds such as arsenate (iAs(V)), monomethylarsonic acid (MMA(V))
      and dimethylarsinic acid (DMA(V)). It has been reported that arsenic-glutathione
      (As-GSH) complexes such as arsenic triglutathione (ATG) and methylarsenic
      diglutathione (MADG) are major metabolites in rat bile following intravenous
      administration of iAs(III). Recently, we have shown that both ATG and MADG are
      unstable and easily hydrolyzed to iAs(III) and MMA(III), respectively, and that
      MMA(III) is oxidized to MMA(V) in bile. In the present study we report the
      effects of H(2)O(2) and GSH on the stability of As-GSH complexes in rat bile.
      Male SD rats were injected intravenously with saline or iAs(III) at a dose of 0.2
      or 2.0 mg As/kg body weight, and bile fluid was collected on ice for 30 min. To
      estimate the stability of As-GSH complexes in bile, ATG or MADG was added to
      untreated, heat-treated, catalase-treated, or dialyzed bile, and then incubated
      at 37 degrees C for 10 min. Concentrations of biliary H(2)O(2) and GSH in the
      higher dose group were 12.6- and 4.5-times higher than the control value,
      respectively. Exogenously added trivalent arsenicals were oxidized to pentavalent
      arsenicals in the bile depending on the biliary concentration of H(2)O(2). Both
      catalase and dialysis prevented oxidation of trivalent arsenicals to the
      corresponding pentavalent compounds. Exogenously added GSH stabilized As-GSH
      complexes in bile. These results suggest that H(2)O(2) converts trivalent
      arsenicals to less toxic pentavalent arsenicals, whereas GSH prevents hydrolysis
      of As-GSH complexes and the generation of unconjugated toxic trivalent
      arsenicals.

PMID- 18619987
TI  - Secretory phospholipases A(2) isolated from Bothrops asper and from Crotalus
      durissus terrificus snake venoms induce distinct mechanisms for biosynthesis of
      prostaglandins E2 and D2 and expression of cyclooxygenases.
AB  - The effects of myotoxin III (MT-III), a phospholipase A(2) (sPLA2) from Bothrops
      asper snake venom, and crotoxin B (CB), a neurotoxic and myotoxic sPLA2 from the
      venom of Crotalus durissus terrificus, on cyclooxygenases (COXs) expression and
      biosynthesis of prostaglandins (PGs) were evaluated, together with the mechanisms
      involved in these effects. Upon intraperitoneal injection in mice, both sPLA(2)s
      promoted the synthesis of PGD2 and PGE2, with a different time-course. MT-III,
      but not CB, induced COX-2 expression by peritoneal leukocytes without
      modification on COX-1 constitutive expression, whereas CB increased the
      constitutive activity of COX-1. MT-III increased the enzymatic activity of COX-1
      and COX-2. Similar effects were observed when these sPLA(2)s were incubated with
      isolated macrophages, evidencing a direct effect on these inflammatory cells.
      Moreover, both toxins elicited the release of arachidonic acid from macrophages
      in vitro. Inhibition of cPLA2 by AACOCF3, but not of iPLA2 by PACOCF3 or BEL,
      significantly reduced PGD2, PGE2 and arachidonic acid (AA) release promoted by MT
      III. These inhibitors did not affect MT-III-induced COX-2 expression. In
      contrast, cPLA2 inhibition did not modify the effects of CB, whereas iPLA2
      inhibition reduced PGD2 and AA production induced by CB. These findings imply
      that distinct regulatory mechanisms leading to PGs' synthesis are triggered by
      these snake venom sPLA(2)s. Such differences are likely to explain the dissimilar
      patterns of inflammatory reaction elicited by these sPLA(2)s in vivo.

PMID- 18619988
TI  - Beta-Bungarotoxin induction of neurite outgrowth in NB41A3 cells.
AB  - In this study, different concentrations of beta-Bgt were used to treat cultured
      NB41A3 cells. Inverted phase contrast microscopy was then used 24h after
      treatment to observe the outgrowth of neurite. We found a clear outgrowth of
      neurite at beta-Bgt concentrations of 357 nM. However, using a cytotoxicity assay
      to study apoptosis, we found no significant difference in the rate of cell death
      in cell cultures treated with either 357 nM or 714 nM. Western blotting showed
      that after treatment with beta-Bgt, there was a notable decrease in small G
      protein Cdc42 and a marked increase in RhoA protein. Flow cytometry revealed that
      beta-Bgt did not alter the calcium influx in NB41A3 cells. The neurite outgrowth
      induced by beta-Bgt was not affected by extracellular EGTA, suggesting that the
      internalization of beta-Bgt from extracellular was independent of phospholipase.
      Taken together, our results suggest the beta-Bgt-induced outgrowth of neurite
      from NB41A3 cells may be mediated by small G proteins.

PMID- 18619989
TI  - Determination of paralytic shellfish poisoning toxins in Norwegian shellfish by
      liquid chromatography with fluorescence and tandem mass spectrometry detection.
AB  - A novel extraction and clean-up method has been developed for the determination
      of paralytic shellfish poisoning (PSP) toxins in shellfish samples. Raw shellfish
      material was extracted with an acidic acetonitrile/water (80:20, v/v) solution,
      whilst being homogenised. During the homogenisation the sample extraction
      solution was cooled with ice water. Subsequently, the extract was frozen at -20
      degrees C for at least 4h. During freezing, two layers were formed, only the
      lower predominantly aqueous layer was used for the determination. The final
      extract solution was cleaned-up using a combination of Oasis HLB and Carbograph
      activated carbon SPE columns. The developed extraction and clean-up methods
      combined with gradient elution liquid chromatography (LC)-mass spectrometry/mass
      spectrometry (MS/MS) has resulted in a method which can determine the analogs GTX
      1-5, C1-2, DcGTX 2-3, DcSTX, Neo, STX in a single analysis with an overall
      detection limit of 313 microg STXdiHCL-eq./kg shellfish meat. The use of the
      developed extraction method with post-column high performance liquid
      chromatography (HPLC) with fluorescence detection (FLD) method provided an
      overall limit of detection of 89 microg STXdiHCL-eq./kg shellfish meat for the
      same toxins. Both post-column HPLC-FLD and LC-MS/MS was used to investigate the
      Norwegian PSP toxin profile. It was found that the PSP toxins could be detected
      in shellfish samples from the Norwegian coastline for 10 months of the year, from
      March till December. The toxin profile consisted mainly of the carbamate toxins,
      GTX 1-4, Neo and STX, in terms of both concentrations and contribution to the
      overall toxicity. In addition, several of the n-sulfo-carbamoyl toxins were
      either detected in the samples at relatively low concentrations or their presence
      in the samples were indicated but could not be confirmed by the post-column HPLC
      FLD and LC-MS/MS analyses.

PMID- 18619990
TI  - Profiles and levels of fatty acid esters of okadaic acid group toxins and
      pectenotoxins during toxin depuration. Part II: blue mussels (Mytilus edulis) and
      flat oyster (Ostrea edulis).
AB  - Bivalve molluscs accumulate toxins of the okadaic acid (OA) and pectenotoxin
      (PTX) groups, which are frequently found in Dinophysis spp. Transformation of the
      OA-group toxins into fatty acid ester derivatives (often designated "DTX3") is
      common in many bivalve species but the degree to which these toxins are
      transformed vary between species, and is also depending on the parent toxin
      involved. In this paper, detailed profiles and levels of fatty acid esters of OA,
      DTX1, DTX2 and PTX2 SA were studied in blue mussels (Mytilus edulis) and European
      flat oysters (Ostrea edulis), collected during a bloom of Dinophysis spp. and
      after 3 and 6 weeks of depuration. Analysis of samples by HPLC-MS/MS and HPLC
      MS(2) revealed some differences in identity and abundance of fatty acid moieties
      of the OA-group esters between species, but the 16:0 fatty acid esters dominated
      in both oysters and mussels, which is in accordance with the free fatty acid
      profiles in these species. A wider range of PTX2 SA-esters were detected compared
      to esters of the OA-group toxins in both mussels and oysters, and in oysters,
      both 14:0, 18:4 and 20:5 fatty acid side chains were more common than 16:0. OA
      group toxins were esterified to a larger degree in oysters (83-93%) compared to
      mussels (21-41%), and in mussels a higher proportion of OA was esterified
      compared to DTX1 and DTX2. Contrary to what was observed for OA-group toxins,
      PTX2 SA was esterified to a larger degree in mussels (81%) compared to oysters
      (64%). Calculations of depuration rates for all individual esters of each parent
      compound showed that the esters of DTX1 depurated significantly slower from both
      mussels and oysters compared to esters of OA, DTX2 and PTX2 SA, but overall the
      depuration rates of esters of both toxin group were highly similar for both
      species. This indicated that differences in depuration rates are not causing the
      large species-specific differences in levels and profiles of these toxins.
      Instead, the results for the OA-group toxins suggested that a higher rate of
      esterification in oysters is the main factor causing the observed differences in
      the proportion of esters to free toxin. For PTX2 SA, large differences in ester
      profiles and a higher proportion of esters of PTX2 SA in mussels compared to
      oysters suggested differential assimilation and metabolic rate processes for the
      PTXs compared to OA-group toxins between these species. Hence, although produced
      by the same Dinophysis species, conclusions about the dynamics of one toxin group
      based on results from the other group should be avoided in future studies.

PMID- 18619991
TI  - Involvement of mitochondrial alteration and reactive oxygen species generation in
      Taiwan cobra cardiotoxin-induced apoptotic death of human neuroblastoma SK-N-SH
      cells.
AB  - Naja naja atra cardiotoxin 3 (CTX3) induced apoptotic death on human
      neuroblastoma SK-N-SH cells. The apoptosis signals of CTX3 included reactive
      oxygen species (ROS) generation, disruption of mitochondrial membrane potential
      (DeltaPsim), cytochrome c release to the cytosol and activation of caspase-9 and 
      3. However, CTX3-induced increase in mitochondrial permeability transition was
      not initiated by proteins of the Bcl-2 family. The collapse of DeltaPsim, release
      of cytosolic cytochrome c, production of ROS and subsequent apoptotic cell death
      in CTX-treated cells could not be completely abolished by either N-acetylcysteine
      (ROS scavenger) or cyclosporin A (an inhibitor of mitochondrial permeability
      transition). Co-incubation with rotenone, an inhibitor of mitochondrial electron
      transport chain complexes I, resulted in partial inhibition of CTX3-induced ROS
      generation but not the loss of DeltaPsim. Obviously, the dissipation of DeltaPsim
      was not an upstream event for ROS generation or vice versa. Given that CTX3 was
      able to induce the leakage of isolated mitochondria, our data indicate that CTX3
      induced apoptotic death of SK-N-SH cells is mediated through mitochondrial
      alteration and ROS generation.

PMID- 18619992
TI  - Aminopeptidase activities, oxidative stress and renal function in Crotalus
      durissus terrificus envenomation in mice.
AB  - Acute renal failure is a serious condition of Crotalus bites, which could be
      treated with statins. The effects of Crotalus durissus terrificus venom (vCdt)
      and simvastatin on renal function, oxidative stress and representative plasma,
      urinary and renal aminopeptidase (AP) activities were evaluated in mice. Eighty
      percent LD50 of vCdt caused hyperuricemia and urinary hypoosmolality (100%) and
      hypercreatinemia (60%). Plasma neutral, pyroglutamyl and dipeptidyl IV and renal
      soluble and membrane-bound APs were susceptible to vCdt. Cortical and medullar
      oxidative stress (GSSG/GSH ratio) was increased by vCdt. Simvastatin (3mg/kg body
      wt.) altered urinary creatinine and urea, membranal protein in cortex and
      medulla, plasma neutral and dipeptidyl IV APs and most of renal APs in
      nonenvenomed, and exacerbated hypercreatinemia, but mitigated uricosuria, renal
      oxidative stress and protein increase in envenomed. Hyperuricemia and urinary
      hypoosmolality are early signs of indirect myotoxicity of vCdt with diagnostic
      significance. In kidney, oxidative stress and alteration of protein content and
      AP activities suggest membrane destruction, enzyme release and protein loss,
      which may be due to direct tissue damage. Plasma AP activities might be
      nephrotoxicity markers of C. d. terrificus envenomation. The deleterious effects
      of simvastatin on creatinemia and APs constitute important restrictions to its
      use within the antivenom therapy.

PMID- 18619993
TI  - Pharmacokinetics of the venom of Bothrops erythromelas labeled with 131I in mice.
AB  - Bothrops erythromelas venom (BeV) has been responsible for many snake accidents
      in Brazil. We investigated the plasmatic pharmacokinetic of BeV labeled with
      (131)I in the absence and the presence of anti-Bothrops serum (BAS). A higher
      percentage of BeV plasmatic radioactivity and longer elimination were found in
      the presence of BAS. Our results showed a redistribution of venom from the tissue
      to vascular compartment associated with the treatment of envenomed mice with anti
      venom 15 min after venom injection.

PMID- 18619994
TI  - Profiles and levels of fatty acid esters of okadaic acid group toxins and
      pectenotoxins during toxin depuration. Part I: brown crab (Cancer pagurus).
AB  - In 2002, two outbreaks of diarrhetic shellfish poisoning (DSP) occurred in
      Norway, which was later confirmed to be caused by the consumption of brown crab
      (Cancer pagurus) contaminated predominantly by esters of okadaic acid (OA) after
      feeding on toxic blue mussels (Mytilus edulis). In addition to OA-group toxins,
      pectenotoxins (PTXs) are commonly detected in the toxin-producing algae (i.e.
      Dinophysis). In this paper, an experiment was set up to study the fatty acid
      ester profiles and depuration rates of OA-group toxins and PTXs from C. pagurus
      after feeding on M. edulis containing these toxin groups. OA, DTX1, DTX2 and PTX2
      SA were all detected primarily in the form of fatty acid esters in the crab
      hepatopancreas (HP). Crabs preferentially assimilated toxins of the OA group
      after feeding on the mussels for 1 week. Detailed analysis of the fatty acid
      ester profile in crabs and mussels showed that the ester profiles in the crabs
      differed slightly from profiles of the fatty acid esters in M. edulis, but
      neither ester profile nor ester to free toxin ratio appeared to change in the
      crabs during the first 2 weeks of depuration. Calculations of depuration rates of
      the free forms of toxins resulted in similar reduction rates for OA and DTX2,
      whereas the depuration rate of DTX1, PTX2 and PTX2 SA was considerably faster.
      From the industrial perspective, the PTX-compounds are of minor importance
      compared to the OA group toxins in crabs, considering (1) the uncertainty
      regarding the oral toxicity of the PTXs, (2) the preferential ingestion of OA
      group toxins compared to PTXs and (3) the faster depuration of PTXs.

PMID- 18619995
TI  - Indoxyl sulfate, a uremic toxin, is biotransformed from indoxyl-beta-D-glucoside
      (indican) in rats.
AB  - Indican (Indoxyl-beta-D-glucoside) is present in many Chinese herbs such as
      Isatis indigotica, Clerodendrum crytophyllum, Glehnia littoralis, Polygonum
      tinctorium and P. perfoliatum. This study aims to investigate whether indoxyl
      sulfate, a uremic toxin, would be biotransformed from indican in rats. Indican
      was administered intravenously and orally to Sprague-Dawley rats. The blood
      samples were withdrawn via cardiopuncture at specific time points and the serum
      concentrations of indican and indoxyl sulfate were assayed by HPLC method. The
      results showed that indican was rapidly and extensively metabolized to indoxyl
      sulfate either given intravenously or orally. Indoxyl sulfate showed markedly
      higher systemic exposure than indican. Because indoxyl sulfate is a harmful
      uremic toxin, we suggest that the content of indican in the aforementioned
      medicinal plants be quantitated and well controlled to ensure the safety for
      clinical use.

PMID- 18619996
TI  - Combined effects of spatial and feature-based attention on responses of V4
      neurons.
AB  - Attention is thought to be controlled by a specialized fronto-parietal network
      that modulates the responses of neurons in sensory and association cortex.
      However, the principles by which this network affects the responses of these
      sensory and association neurons remains unknown. In particular, it remains
      unclear whether different forms of attention, such as spatial and feature-based
      attention, independently modulate responses of single neurons. We recorded
      responses of single V4 neurons in a task that controls both forms of attention
      independently. We find that the combined effects of spatial and feature-based
      attention can be described as the sum of independent processes with a small super
      additive interaction term. This pattern of effects demonstrates that the spatial
      and feature-based aspects of the attentional control system can independently
      affect responses of single neurons. These results are consistent with the idea
      that spatial and feature-based attention are controlled by distinct neural
      substrates whose effects combine synergistically to influence responses of visual
      neurons.

PMID- 18619998
TI  - Reliability of doctors' anthropometric measurements to detect obesity.
AB  - OBJECTIVE: To evaluate the reliability of anthropometric measurements (weight,
      height, Body Mass Index (BMI), waist and hip circumferences (WC; HC) and waist-to
      hip ratio (WHR)) performed by doctors to assess obesity. METHOD: Repeated
      anthropometric measurements were performed by 12 primary care physicians on 24
      adult volunteers in Geneva, Switzerland, 2006. Volunteers (54% women, mean age
      41) had a mean BMI of 28.1 (respective mean values for WC, HC and WHR: 91.4,
      108.3, 0.84). Inter-observer reliability coefficient (R) and percent disagreement
      in categorisation of volunteers (normal weight, overweight, obesity, abdominal
      obesity) were computed according to these measurements. RESULTS: The inter
      observer reliability for weight, height, and derived BMI were excellent (R>0.99),
      but unsatisfactory for WC (R=0.92), HC (R=0.76) and WHR (R=0.51). Based on the
      BMI, only 1% of the volunteers were misclassified as overweight or obese, whereas
      the use of WC and WHR lead to misclassification in 6% and 23% respectively.
      Reliability for the measurements improved after a one-hour training in
      anthropometric measurements (R=0.97 for WC, 0.92 for HC and 0.89 for WHR), but
      the proportion who were misclassified remained high despite the training session
      for WC (5%) and WHR (9%). CONCLUSIONS: BMI remains the most reliable measure to
      detect obesity in medical practice, whereas WC, HC and WHR are less reliable.
      These results challenge current recommendations on obesity-related cardio
      vascular risk management based on WC and WHR and underline the need for further
      research to improve the reliability of anthropometric measurements by doctors.

PMID- 18620000
TI  - Novel pharmacological targets based on receptor heteromers.
AB  - Studies performed in the last 10 years have provided solid evidence indicating
      that G-protein-coupled receptors are expressed on the plasma membrane as homo and
      heterodimers. The first consequence of this fact is that homo and heterodimers
      are the true targets of natural (hormones, neurotransmitters) and synthetic
      drugs. Furthermore a given receptor in a heteromer may display a different
      functional and/or pharmacological profile than the same receptor characterized as
      monomer or as homodimer. Recent evidence indicates that receptor heteromers are
      sensors that lead to a fine-tuning in neurotransmission or hormone regulation;
      mainly this is achieved by a modification of the signaling pathways activated via
      a given receptor when it is forming a given heteromer. Quite often antagonists
      display variable affinities when a given receptor is expressed with different
      heteromeric partners. This fact should be taken into account in the development
      of new drugs. Finally it should be pointed out that radioligand binding data has
      to be analyzed by a model that considers receptors as dimers and not as monomers.
      This model provides a novel approach to characterize drugs interacting with the
      orthosteric center (agonists/antagonists) or with allosteric centers (allosteric
      regulators).

PMID- 18619997
TI  - Intrinsic disorder in scaffold proteins: getting more from less.
AB  - Regulation, recognition and cell signaling involve the coordinated actions of
      many players. Signaling scaffolds, with their ability to bring together proteins
      belonging to common and/or interlinked pathways, play crucial roles in
      orchestrating numerous events by coordinating specific interactions among
      signaling proteins. This review examines the roles of intrinsic disorder (ID) in
      signaling scaffold protein function. Several well-characterized scaffold proteins
      with structurally and functionally characterized ID regions are used here to
      illustrate the importance of ID for scaffolding function. These examples include
      scaffolds that are mostly disordered, only partially disordered or those in which
      the ID resides in a scaffold partner. Specific scaffolds discussed include RNase,
      voltage-activated potassium channels, axin, BRCA1, GSK-3beta, p53, Ste5, titin,
      Fus3, BRCA1, MAP2, D-AKAP2 and AKAP250. Among the mechanisms discussed are:
      molecular recognition features, fly-casting, ease of encounter complex formation,
      structural isolation of partners, modulation of interactions between bound
      partners, masking of intramolecular interaction sites, maximized interaction
      surface per residue, toleration of high evolutionary rates, binding site overlap,
      allosteric modification, palindromic binding, reduced constraints for alternative
      splicing, efficient regulation via posttranslational modification, efficient
      regulation via rapid degradation, protection of normally solvent-exposed sites,
      enhancing the plasticity of interaction and molecular crowding. We conclude that
      ID can enhance scaffold function by a diverse array of mechanisms. In other
      words, scaffold proteins utilize several ID-facilitated mechanisms to enhance
      function, and by doing so, get more functionality from less structure.

PMID- 18619999
TI  - Stress, depression, and coronary artery disease: modeling comorbidity in female
      primates.
AB  - Depression and coronary heart disease (CHD) are leading contributors to disease
      burden in women. CHD and depression are comorbid; whether they have common
      etiology or depression causes CHD is unclear. The underlying pathology of CHD,
      coronary artery atherosclerosis (CAA), is present decades before CHD, and the
      temporal relationship between depression and CAA is unclear. The evidence of
      involvement of depression in early CAA in cynomolgus monkeys, an established
      model of CAA and depression, is summarized. Like people, monkeys may respond to
      the stress of low social status with depressive behavior accompanied by
      perturbations in hypothalamic-pituitary-adrenal (HPA), autonomic nervous system,
      lipid metabolism, ovarian, and neural serotonergic system function, all of which
      are associated with exacerbated CAA. The primate data are consistent with the
      hypothesis that depression may cause CAA, and also with the hypothesis that CAA
      and depression may be the result of social stress. More study is needed to
      discriminate between these two possibilities. The primate data paint a compelling
      picture of depression as a whole-body disease.

PMID- 18620001
TI  - Essential role of Toll-like receptors for dendritic cell and NK1.1(+) cell
      dependent activation of type 1 immunity by Lactobacillus pentosus strain S-PT84.
AB  - Activation of type 1 immunity plays a critical role in host defense mechanisms
      against infectious disease and tumor. Lactic acid bacteria, existing in the
      gastrointestinal tract, are one of the powerful tools to induce a type-1-dominant
      immunity, which may improve Th2-dependent allergic diseases. In the present work,
      we found that an oral intake of Lactobacillus pentosus strain, S-PT84 into mice
      significantly enhanced NK activity of spleen cells in vivo. We further revealed
      that NK1.1 positive NK cells and NKT cells are responsible cells for producing
      IFN-gamma after stimulation with S-PT84 in vitro. S-PT84 induced IFN-gamma
      producing cells through activation of IL-12 production by CD11c(+)DCs in Toll
      like receptor (TLR) 2- and/or TLR4-dependent manner. Interestingly, direct
      interaction between DCs and NK1.1(+) cells was also essential for the IFN-gamma
      production in response to the S-PT84 stimulation. Therefore, we concluded that S
      PT84 effectively promoted type 1 immunity through IL-12 and IFN-gamma which were
      produced by DCs and NK1.1(+) cells, respectively. Thus, S-PT84 would be a nice
      immune modulator for improving immunobalance, which plays a pivotal role for
      controlling allergy, infectious diseases and tumor.

PMID- 18620002
TI  - The Fasciola hepatica thioredoxin: High resolution structure reveals two
      oxidation states.
AB  - The Fasciola hepatica thioredoxin protein structure has been determined to 1.45A
      resolution. This is the first example of a single crystal structure to show the
      active site cysteine residues in both the reduced and disulfide oxidised form.
      Consistent with this observation the process of oxidation appears to require very
      little rearrangement of the surrounding protein structure. The F. hepatica
      thioredoxin structure has been compared to other thioredoxin protein structures
      already known and is found to be highly conserved. The F. hepatica protein is
      most similar to that of the thioredoxin from its human and animal hosts but it
      resembles other parasitic thioredoxins with regard to having no additional
      cysteine residues and is therefore not regulated by transient disulfide bond
      formation as proposed for thioredoxins from higher eukaryotic species.

PMID- 18620003
TI  - Activation of submucosal but not myenteric plexus of the gastrointestinal tract
      accompanies reduction of food intake by camostat.
AB  - It has been shown in the rat that endogenous cholecystokinin (CCK), released in
      response to the non-nutrient trypsin inhibitor camostat, reduces food intake at
      meals and increases Fos-like immunoreactivity (Fos-LI; a marker for neuronal
      activation) in the dorsal vagal complex (DVC) of the hindbrain but not the
      myenteric plexus of the duodenum and jejunum. Experiment 1: We examined Fos-LI in
      the myenteric and the submucosal plexuses of the gut in response to orogastric
      gavage of camostat in rats. As we reported previously, camostat failed to
      increase Fos-LI in the myenteric plexus. We show here that camostat increased Fos
      LI in the submucosal plexus of the duodenum and jejunum. Camostat also increased
      Fos-LI in the DVC. Experiment 2: Pretreatment with devazepide, a specific CCK(1)
      receptor antagonist abolished camostat-induced Fos-LI in the submucosal plexus
      and the DVC. Experiment 3: Bilateral subdiaphragmatic vagotomy reduced camostat
      induced Fos-LI in the submucosal plexus approximately 40% and abolished it in the
      DVC. CONCLUSIONS: Activation of the submucosal plexus by cholecystokinin at the
      CCK(1) receptor accompanies stimulation of the dorsal vagal complex of the
      hindbrain and inhibition of food intake. Unlike the submucosal plexus, activation
      of the myenteric plexus is not necessary for cholecystokinin's influence on the
      dorsal vagal complex and food intake. The lack of activation in the myenteric
      plexus after camostat stimulation, in contrast to nutrient releasers of CCK such
      as oleate, suggests that intestinal stimulants can either release different
      amounts of CCK or cause release of CCK from I cells with different molecular
      forms of CCK. This would suggest that CCK-8 is released by camostat and is not
      able to travel to the myenteric plexus while a more stable form of CCK such as
      CCK-58 can travel to this site that is further away from the I cell.

PMID- 18620004
TI  - Cristae formation-linking ultrastructure and function of mitochondria.
AB  - Mitochondria are double-membrane enclosed eukaryotic organelles with a central
      role in numerous cellular functions. The ultrastructure of mitochondria varies
      considerably between tissues, organisms, and the physiological state of cells.
      Alterations and remodeling of inner membrane structures are evident in numerous
      human disorders and during apoptosis. The inner membrane is composed of two
      subcompartments, the cristae membrane and the inner boundary membrane. Recent
      advances in electron tomography led to the current view that these membrane
      domains are connected by rather small tubular structures, termed crista
      junctions. They have been proposed to regulate the dynamic distribution of
      proteins and lipids as well as of soluble metabolites between individual
      mitochondrial subcompartments. One example is the release of cytochrome c upon
      induction of apoptosis. However, only little is known on the molecular mechanisms
      mediating the formation and maintenance of cristae and crista junctions. Here we
      review the current knowledge of the factors that determine cristae morphology and
      how the latter is linked to mitochondrial function. Further, we formulate several
      theoretical models which could account for the de novo formation of cristae as
      well as their propagation from existing cristae.

PMID- 18620005
TI  - Identification of a functional interaction between Kv4.3 channels and c-Src
      tyrosine kinase.
AB  - Voltage-gated K(+) (Kv) channels are key determinants of cardiac and neuronal
      excitability. A substantial body of evidence has accumulated in support of a role
      for Src family tyrosine kinases in the regulation of Kv channels. In this study,
      we examined the possibility that c-Src tyrosine kinase participates in the
      modulation of the transient voltage-dependent K(+) channel Kv4.3. Supporting a
      mechanistic link between Kv4.3 and c-Src, confocal microscopy analysis of HEK293
      cells stably transfected with Kv4.3 showed high degree of co-localization of the
      two proteins at the plasma membrane. Our results further demonstrate an
      association between Kv4.3 and c-Src by co-immunoprecipitation and GST pull-down
      assays, this interaction being mediated by the SH2 and SH3 domains of c-Src.
      Furthermore, we show that Kv4.3 is tyrosine phosphorylated under basal
      conditions. The functional relevance of the observed interaction between Kv4.3
      and c-Src was established in patch-clamp experiments, where application of the
      Src inhibitor PP2 caused a decrease in Kv4.3 peak current amplitude, but not the
      inactive structural analogue PP3. Conversely, intracellular application of
      recombinant c-Src kinase or the protein tyrosine phosphatase inhibitor bpV(phen)
      increased Kv4.3 peak current amplitude. In conclusion, our findings provide
      evidence that c-Src-induced Kv4.3 channel activation involves their association
      in a macromolecular complex and suggest a role for c-Src-Kv4.3 pathway in
      regulating cardiac and neuronal excitability.

PMID- 18620006
TI  - Assembly of the oxidative phosphorylation system in humans: what we have learned
      by studying its defects.
AB  - Assembly of the oxidative phosphorylation (OXPHOS) system in the mitochondrial
      inner membrane is an intricate process in which many factors must interact. The
      OXPHOS system is composed of four respiratory chain complexes, which are
      responsible for electron transport and generation of the proton gradient in the
      mitochondrial intermembrane space, and of the ATP synthase that uses this proton
      gradient to produce ATP. Mitochondrial human disorders are caused by dysfunction
      of the OXPHOS system, and many of them are associated with altered assembly of
      one or more components of the OXPHOS system. The study of assembly defects in
      patients has been useful in unraveling and/or gaining a complete understanding of
      the processes by which these large multimeric complexes are formed. We review
      here current knowledge of the biogenesis of OXPHOS complexes based on
      investigation of the corresponding disorders.

PMID- 18620007
TI  - Mitochondrial ATP synthase disorders: molecular mechanisms and the quest for
      curative therapeutic approaches.
AB  - In mammals, the majority of cellular ATP is produced by the mitochondrial F1F(O)
      ATP synthase through an elaborate catalytic mechanism. While most subunits of
      this enzymatic complex are encoded by the nuclear genome, a few essential
      components are encoded in the mitochondrial genome. The biogenesis of this multi
      subunit enzyme is a sophisticated multi-step process that is regulated on levels
      of transcription, translation and assembly. Defects that result in diminished
      abundance or functional impairment of the F1F(O)-ATP synthase can cause a variety
      of severe neuromuscular disorders. Underlying mutations have been identified in
      both the nuclear and the mitochondrial DNA. The pathogenic mechanisms are only
      partially understood. Currently, the therapeutic options are extremely limited.
      Alternative methods of treatment have however been proposed, but still encounter
      several technical difficulties. The application of novel scientific approaches
      promises to deepen our understanding of the molecular mechanisms of the ATP
      synthase, unravel novel therapeutic pathways and improve the unfortunate
      situation of the patients suffering from such diseases.

PMID- 18620008
TI  - Effects of tobacco smoking and schizotypal personality on spectral contents of
      spontaneous EEG.
AB  - Effects of chronic tobacco smoking on the spectral contents of spontaneous
      electroencephalogram (EEG) were examined in connection with schizotypal
      personality. EEG recorded from 19 smokers and 20 non-smokers college students
      were studied by means of parametric spectral estimation followed by a statistical
      analysis of differences. We observed that tobacco smoking affects EEG of high and
      low schizotypy individuals differently. Tobacco smoking may (with the probability
      exceeding 95%) lead to an increase in high frequency contents of EEG while
      evaluated for low schizotypy participants. For high schizotypy individuals, on
      the other hand, the most pronounced changes associated with smoking (increase of
      EEG power) arose in the low frequency rhythms. The most significant changes in
      spontaneous EEG-as attributed to smoking-were observed in the occipital region
      for both groups of high and low schizotypy participants. The observations are
      consistent with the finding reported on the schizophrenia patients and partially
      support the nicotine self-medication model.

PMID- 18620009
TI  - Mutational events during the primary propagation and consecutive passages of
      hepatitis E virus strain JE03-1760F in cell culture.
AB  - We recently developed a cell culture system for hepatitis E virus (HEV) in
      PLC/PRF/5 cells, using a genotype 3 HEV (JE03-1760F strain). Thirteen generations
      of consecutive passages of culture supernatant were successfully carried out in
      PLC/PRF/5 cells, with the highest HEV load reaching 10(8) copies/ml in the
      culture medium. Based on continuous release of progenies into culture medium, 50%
      tissue culture infectivity doses were estimated to be 2.0 x 10(3) copies for wild
      type JE03-1760F and 1.4 x 10(2) copies for p13 (progeny in the thirteenth
      passage). Earlier appearance and greater increase in the yield of progenies in
      the culture supernatant were evident in p13 compared with wild-type. The cell
      culture-produced variants in primary propagation (p0) and consecutive passages
      (p5 [fifth passage], p10 [tenth], and p13) differed from the wild-type virus by
      1, 9, 18, and 19 nucleotides (nt), respectively, over the entire genome of
      7226nt, excluding the poly(A) tail. Three of five non-synonymous mutations in p13
      were shared by a variant (fifth passage) in another series of passages of JE03
      1760F. These results suggest that adaptation of HEV variants to growth in vitro
      is associated with a limited number of mutations similar to hepatitis A virus.

PMID- 18620010
TI  - Cross-reactive and serospecific epitopes of nucleocapsid proteins of three
      hantaviruses: prospects for new diagnostic tools.
AB  - The diagnosis of infectious diseases is sometimes difficult because of extensive
      immunological cross-reactivity between related viral antigens. On the path of
      constructing sero-specific antigens, we have identified residues involved in sero
      specific and cross-reactive recognition of the nucleocapsid proteins (NPs) of
      Puumala virus (PUUV), Seoul virus (SEOV), and Sin Nombre virus (SNV) using serum
      samples from 17 Nephropathia epidemica patients. The mapping was performed by
      enzyme-linked immunosorbent assay (ELISA) and Western blot analysis on a panel of
      N protein derivatives and alanine-substitution mutants in the three different
      hantavirus backgrounds. Four regions with different serological profiles were
      identified encompassing the amino acids (aa) 14-17, 22-24, 26, and 35-38. One of
      the regions showed strong cross-reactivity and was important for the recognition
      of SEOV and SNV antigens, but not the PUUV antigen (aa 35-38). Two regions
      displayed perceivable SEOV characteristics (aa 14-17 and aa 22-24 and 26) and the
      combined result of the alanine replacements resulted in a synergetic effect
      against the PUUV antigen (aa 14-17, 22-24, 26).

PMID- 18620011
TI  - Formulating erythropoietin-loaded sustained-release PLGA microspheres without
      protein aggregation.
AB  - We report a simple method to microencapsulate erythropoietin (EPO, a protein
      easily denatured and antigenized by contact with water-organic solvent
      interfaces) into poly(lactic-co-glycolic acid) (PLGA) microspheres with minimal
      aggregation. This formulation process involved an aqueous-aqueous emulsion formed
      at reduced temperature. EPO was first dissolved in water together with dextran
      (MW=70,000) and polyethylene glycol (MW=8000), followed by a freezing process
      during which dextran separated out as the dispersed phase with EPO partitioned in
      preferentially. The frozen sample was then lyophilized to powder and washed with
      dichloromethane to remove the PEG continuous phase. Once loaded in the
      polysaccharide particles, 1-4 microm in diameter, EPO gained resistance to
      organic solvents and was encapsulated into PLGA microspheres without significant
      aggregation (<2%). EPO released from the composite PLGA microspheres in a
      sustained-release manner with minimal burst (<20% at the first day) and
      incomplete (<20%) release. Single injection of these EPO-loaded PLGA microspheres
      to mice resulted in a red blood cell elevation equivalent to twelve injections of
      the solution formulation. An ELISA assay suggested that the mice injected with
      the EPO-loaded PLGA microspheres did not develop anti-EPO IgG more than those
      given solution form EPO.

PMID- 18620012
TI  - Identification and characterization of novel reptile cathelicidins from elapid
      snakes.
AB  - Three cDNA sequences coding for elapid cathelicidins were cloned from constructed
      venom gland cDNA libraries of Naja atra, Bungarus fasciatus and Ophiophagus
      hannah. The open reading frames of the cloned elapid cathelicidins were all
      composed of 576bp and coded for 191 amino acid residue protein precursors. Each
      of the deduced elapid cathelicidin has a 22 amino acid residue signal peptide, a
      conserved cathelin domain of 135 amino acid residues and a mature antimicrobial
      peptide of 34 amino acid residues. Unlike the highly divergent cathelicidins in
      mammals, the nucleotide and deduced protein sequences of the three cloned elapid
      cathelicidins were remarkably conserved. All the elapid mature cathelicidins were
      predicted to be cleaved at Valine157 by elastase. OH-CATH, the deduced mature
      cathelicidin from king cobra, was chemically synthesized and it showed strong
      antibacterial activity against various bacteria with minimal inhibitory
      concentration of 1-20microg/ml in the presence of 1% NaCl. Meanwhile, the
      synthetic peptide showed no haemolytic activity toward human red blood cells even
      at a high dose of 200microg/ml. Phylogenetic analysis of cathelicidins from
      vertebrate suggested that elapid and viperid cathelicidins were grouped together
      in the tree. Snake cathelicidins were evolutionary closely related to the
      neutrophilic granule proteins (NGPs) from mouse, rat and rabbit. Snake
      cathelicidins also showed a close relationship with avian fowlicidins (1-3) and
      chicken myeloid antimicrobial peptide 27. Elapid cathelicidins might be used as
      models for the development of novel therapeutic drugs.

PMID- 18620013
TI  - Hyper-responsiveness of adrenal gland to vasopressin resulting in enhanced plasma
      cortisol in patients with adrenal nodule(s).
AB  - Hyper-responsiveness of plasma cortisol to vasopressin has been demonstrated in
      ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) and
      some adrenal adenomas with Cushing's syndrome (CS). However, the clinical
      significance of hyper-responsiveness of plasma cortisol to vasopressin has not
      been investigated systematically in adrenal nodule(s). The aim of this study was
      to clarify the prevalence of hyper-responsiveness of plasma cortisol to
      vasopressin (vasopressin responder) and their clinical characteristics in terms
      of hormonal secretion using vasopressin-loading test in the patients with adrenal
      nodule(s) except pheochromocytomas. A vasopressin-loading test was performed on
      61 consecutive patients with adrenal nodules (CS: 33, aldosterone-producing
      adenoma: 10, non-functional tumor: 18). Vasopressin responders were observed in
      36.1% of adrenal nodule(s), 42.4% of CS and 28.5% of non-CS. In responders with
      CS, eight patients had bilateral nodules that were diagnosed as AIMAH, and the
      remaining six patients had a unilateral nodule. These patients had lower plasma
      cortisol than non-responders at both morning (P<0.01) and midnight (P<0.05), as
      well as the morning following overnight dexamethasone suppression at 1mg (P<0.05)
      and 8mg (P<0.05). Hyper-responsiveness of the adrenal gland to vasopressin
      resulting in enhanced plasma cortisol was frequently observed among patients with
      adrenal nodule(s). The vasopressin responders among the patients with adrenal
      nodule(s) frequently had CS with low autonomous cortisol secretion.

PMID- 18620014
TI  - Caffeine improves adult mice performance in the object recognition task and
      increases BDNF and TrkB independent on phospho-CREB immunocontent in the
      hippocampus.
AB  - Caffeine is one of the most psychostimulants consumed all over the world that
      usually presents positive effects on cognition. In this study, effects of
      caffeine on mice performance in the object recognition task were tested in
      different intertrial intervals. In addition, it was analyzed the effects of
      caffeine on brain derived neurotrophic factor (BDNF) and its receptor, TrkB,
      immunocontent to try to establish a connection between the behavioral finding and
      BDNF, one of the neurotrophins strictly involved in memory and learning process.
      CF1 mice were treated during 4 consecutive days with saline (0.9g%, i.p.) or
      caffeine (10mg/kg, i.p., equivalent dose corresponding to 2-3 cups of coffee).
      Caffeine treatment was interrupted 24h before the object recognition task
      analysis. In the test session performed 15min after training session, caffeine
      treated mice recognized more efficiently both the familiar and the novel object.
      In the test session performed 90min and 24h after training session, caffeine did
      not change the time spent in the familiar object but increased the object
      recognition index, when compared to control group. Western blotting analysis of
      hippocampus from caffeine-treated mice revealed an increase in BDNF and TrkB
      immunocontent, compared to their saline-matched controls. Phospho-CREB
      immunocontent did not change with caffeine treatment. Our results suggest that
      acute treatment with caffeine improves recognition memory, and this effect may be
      related to an increase of the BDNF and TrkB immunocontent in the hippocampus.

PMID- 18620015
TI  - Are adolescents ready for tuberculosis vaccine trials?
AB  - Tuberculosis (TB) vaccine trials are planned in adolescents in a high
      tuberculosis burden rural area near Cape Town, South Africa. To determine the
      knowledge and attitudes of adolescents about tuberculosis, vaccines and vaccine
      trials, a representative sample of adolescent learners was chosen from high
      schools in the trial area. A questionnaire was administered and focus group
      discussions held with the group and a sample of their parents. The questionnaire
      response rate was 65%. Knowledge of tuberculosis was fair 63.7% but knowledge of
      vaccines poor 41.9% based on a TB and vaccine knowledge score, respectively.
      Willingness to participate in vaccine trials will be influenced by the type of
      procedures involved (60% willing to answer questions, 43% willing to be examined,
      32% willing to undergo skin tests and 39% willing to undergo blood draw). In
      general, better knowledge was statistically associated with greater willingness
      to participate in study procedures except for the blood draw. The focus group
      discussions showed that adolescents and their parents were positive about
      participating in vaccine trials but concerns about safety and the provision of
      adequate information should be considered when planning TB vaccine trials. This
      study suggests that TB vaccine trials would be acceptable amongst adolescents in
      this community with certain provisos.

PMID- 18620016
TI  - Co-morbidities associated with influenza-attributed mortality, 1994-2000, Canada.
AB  - The elderly and persons with specific chronic conditions are known to face
      elevated morbidity and mortality risks resulting from an influenza infection, and
      hence are routinely recommended for annual influenza vaccination. However, risk
      specific mortality rates have not been established. We estimated age-specific
      influenza-attributable mortality rates stratified by the presence of chronic
      conditions and type of residence based on deaths of persons who were admitted to
      hospital with a respiratory complication captured in our national database. The
      majority of patients had chronic heart or respiratory conditions (80%) and were
      admitted from the community (80%). Influenza-attributable mortality rates clearly
      increase with age for all risk groups. Our influenza-specific estimates
      identified higher risk ratios for chronic lung or heart disease than have been
      suggested by other methods. These estimates identify groups most in need of
      improved vaccines and for whom the use of additional strategies, such as
      immunization of household contacts or caregivers should be considered.

PMID- 18620017
TI  - Efficacy and bait acceptance of vaccinia vectored rabies glycoprotein vaccine in
      captive foxes (Vulpes vulpes), raccoon dogs (Nyctereutes procyonoides) and dogs
      (Canis familiaris).
AB  - The red fox, dog, and raccoon dog are known to play a major role in the global
      epidemiology of rabies. These three canid species were used to compare the
      appetency and efficacy of two commercial bait formats, each containing a single
      dose of vaccinia-rabies glycoprotein (V-RG) vaccine. Square and rectangular
      RABORAL V-RG baits were fed to individual caged animal, and results were
      evaluated using three parameters: bait consumption, induction of rabies virus
      neutralizing antibodies and protection after a virulent rabies challenge. The
      rectangular and square RABORAL V-RG baits were found to deliver the oral rabies
      vaccine in a similar manner to all three species resulting in acceptable
      seroconversion and effective protection levels after the rabies challenge.
      Appetency of each bait type was measured by bait consumption and found to be
      similar for both RABORAL V-RG bait formats in the fox and dog. The square RABORAL
      V-RG bait, however, was consumed more effectively than the rectangular RABORAL V
      RG bait by the raccoon dog.

PMID- 18620018
TI  - Synergistic effects of ferritin and propolis in modulation of beryllium induced
      toxicogenic alterations.
AB  - Synergistic therapeutic potential of ferritin (5mg/kg, i.p.) and propolis
      (honeybee hive product; 200mg/kg, p.o.) was analyzed to encounter the beryllium
      induced biochemical and ultra morphological alterations. Female albino rats were
      exposed to beryllium nitrate (1mg/kg, i.p.) daily for 28 days followed by
      treatment of above mentioned therapeutic agents either individually or in
      combination for five consecutive days. Exposure to beryllium increased its
      concentration in serum, liver and kidney and significantly altered the activities
      of CYP2E1 and CYP1A2 enzymes, microsomal lipid peroxidation and microsomal
      proteins. Activities of aspartate aminotransferase, alanine aminotransferase,
      alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase,
      bilirubin, protein, creatinine and urea in serum as well as hemoglobin and blood
      glucose level; activity of acid phosphatase, alkaline phosphatase, adenosine
      triphosphatase, glucose-6-phosphatase and succinic dehydrogenase, total
      triglycerides, total cholesterol, total protein contents, glycogen contents,
      lipid peroxidation and glutathione level in liver and kidney were significantly
      altered after beryllium administration. Beryllium exposure severely altered
      ultramorphology of liver and kidney that proved its toxic consequences at
      cellular level. Ferritin in combination with propolis dramatically reversed the
      alterations of these variables towards control in a synergistic manner concluding
      its beneficial effects over monotherapy in attenuating beryllium induced systemic
      toxicity.

PMID- 18620019
TI  - Sartan-AT1 receptor interactions: in vitro evidence for insurmountable antagonism
      and inverse agonism.
AB  - Sartans are non-peptide AT(1) receptor antagonists used to treat hypertension and
      related pathologies. Their effects on the G protein-dependent responses of
      angiotensin II (Ang II) were the same in vascular tissues and in isolated cell
      systems. All are competitive but, when pre-incubated, they act surmountably (only
      rightward shift of the Ang II concentration-response curve) or insurmountably
      (also decreasing the maximal response). Insurmountable behaviour reflects the
      formation of tight sartan-receptor complexes; it is often partial due to the co
      existence of tight and loose complexes. Their ratio positively correlates with
      the dissociation half-life of the tight complexes and depends on the sartan: i.e.
      candesartan>olmesartan>telmisartan approximately equal
      EXP3174>valsartan>irbesartan>>losartan. When AT(1) receptors display sufficient
      basal activity (in case of receptor over-expression, mutation and, especially,
      tissue stretching) sartans may also act as inverse agonists. This rather affects
      long-term, G protein-independent hypertrophic responses leading to cardiovascular
      remodelling.

PMID- 18620020
TI  - Hormone affinity and fibril formation of piscine transthyretin: the role of the N
      terminal.
AB  - Transthyretin (TTR) transports thyroid hormones (THs), thyroxine (T4) and
      triiodothyronine (T3) in the blood of vertebrates. TH-binding sites are highly
      conserved in vertebrate TTR, however, piscine TTR has a longer N-terminus which
      is thought to influence TH-binding affinity and may influence TTR stability. We
      produced recombinant wild type sea bream TTR (sbTTRWT) plus two mutants in which
      6 (sbTTRM6) and 12 (sbTTRM12) N-terminal residues were removed. Ligand-binding
      studies revealed similar affinities for T3 (Kd=10.6+/-1.7nM) and T4 (Kd=9.8+/
      0.97nM) binding to sbTTRWT. Affinity for THs was unaltered in sbTTRM12 but
      sbTTRM6 had poorer affinity for T4 (Kd=252.3+/-15.8nM) implying that some
      residues in the N-terminus can influence T4 binding. sbTTRM6 inhibited acid
      mediated fibril formation in vitro as shown by fluorometric measurements using
      thioflavine T. In contrast, fibril formation by sbTTRM12 was significant,
      probably due to decreased stability of the tetramer. Such studies also suggested
      that sbTTRWT is more resistant to fibril formation than human TTR.

PMID- 18620021
TI  - DOPA cyclohexyl ester, a DOPA antagonist, blocks the depressor responses elicited
      by microinjections of nicotine into the nucleus tractus solitarii of rats.
AB  - Nicotinic cholinergic receptors play a role in cardiovascular regulation in the
      lower brain stem. Herein, we present evidence that l-3,4-dihydroxyphenylalanine
      (DOPA), a putative neurotransmitter in the central nervous system, is involved in
      the depressor response to microinjection of nicotine into the nucleus tractus
      solitarii (NTS). Microinjection of nicotine into the medial area of the NTS led
      to decreases in arterial blood pressure and heart rate in anesthetized rats.
      Mecamylamine, a nicotinic receptor antagonist, microinjected into NTS, blocked
      the depressor and bradycardic responses to nicotine. Nicotine-induced depressor
      and bradycardic responses were blocked by DOPA cyclohexyl ester (DOPA CHE), an
      antagonist for DOPA. DOPA CHE did not modify the action of carbachol on
      excitatory postsynaptic potential in rat cortical slices. These results suggest
      that endogenous DOPA is involved in nicotine-induced depressor responses in the
      NTS of anesthetized rats.

PMID- 18620022
TI  - A surgical ankle sprain pain model in the rat: effects of morphine and
      indomethacin.
AB  - Ankle sprain is a frequent injury in humans that results in pain, swelling and
      difficulty in walking on the affected side. Currently a suitable animal model
      resembling human ankle sprain is lacking. Here, we describe an animal ankle
      sprain model induced by ankle ligament injury (ALI) in rats. Cutting combinations
      of the lateral ankle ligament complex produced pain, edema and difficulty of
      weight bearing, thereby mimicking severe (grade III) ankle sprain in humans.
      Analgesic compounds, morphine and indomethacin, significantly reversed the
      reduced weight bearing, thus indicating that reduction of weight bearing is
      partially due to pain. The ALI model is a new ankle sprain model that may be
      useful for the study of ankle sprain pain mechanisms and treatments, as well as
      for the screening of new analgesic drugs.

PMID- 18620023
TI  - Effects of topiramate and levetiracetam vs placebo on habituation of contingent
      negative variation in migraine patients.
AB  - Migraine is characterized by reduced habituation of multimodal evoked potentials,
      which in turn reflects an abnormal pattern of cortical excitability. We assessed
      the effects of a 2-month treatment with topiramate or levetiracetam vs placebo on
      contingent negative variation (CNV) habituation and amplitude in a cohort of
      migraine without aura (MO) patients. Forty-five MO patients were selected from a
      university-based outpatient clinic and randomly assigned to 100mg topiramate or
      1000mg levetiracetam or placebo in a double-blind design. Twenty-four control
      subjects were also recruited. The initial CNV (iCNV) amplitude and habituation
      were assessed by Cz/A1-A2 derivation recordings in the basal condition (T0) and
      after 2 months of treatment (T1). Both topiramate and levetiracetam produced a
      significant reduction in migraine frequency compared to placebo, they also
      reversed the abnormal iCNV habituation pattern which characterized the MO
      patients in the basal condition and which was not present in controls. For
      migraine patients, the reduced migraine frequency and habituation index following
      treatment were significantly correlated. A lack of habituation of evoked
      responses is an interictal endophenotypic marker in migraine, the reversion of
      which may improve disease outcome. These results suggest a role for
      neurophysiological methods in the management of migraine.

PMID- 18620024
TI  - Docosahexaenoic acid dietary supplementation enhances the effects of exercise on
      synaptic plasticity and cognition.
AB  - Omega-3 fatty acids (i.e. docosahexaenoic acid; DHA), similar to exercise,
      improve cognitive function, promote neuroplasticity, and protect against
      neurological lesion. In this study, we investigated a possible synergistic action
      between DHA dietary supplementation and voluntary exercise on modulating synaptic
      plasticity and cognition. Rats received DHA dietary supplementation (1.25% DHA)
      with or without voluntary exercise for 12 days. We found that the DHA-enriched
      diet significantly increased spatial learning ability, and these effects were
      enhanced by exercise. The DHA-enriched diet increased levels of pro-brain-derived
      neurotrophic factor (BDNF) and mature BDNF, whereas the additional application of
      exercise boosted the levels of both. Furthermore, the levels of the activated
      forms of CREB and synapsin I were incremented by the DHA-enriched diet with
      greater elevation by the concurrent application of exercise. While the DHA diet
      reduced hippocampal oxidized protein levels, a combination of a DHA diet and
      exercise resulted in a greater reduction rate. The levels of activated forms of
      hippocampal Akt and CaMKII were increased by the DHA-enriched diet, and with even
      greater elevation by a combination of diet and exercise. Akt and CaMKII signaling
      are crucial step by which BDNF exerts its action on synaptic plasticity and
      learning and memory. These results indicate that the DHA diet enhanced the
      effects of exercise on cognition and BDNF-related synaptic plasticity, a capacity
      that may be used to promote mental health and reduce risk of neurological
      disorders.

PMID- 18620025
TI  - Unconditioned stimulus pathways to the amygdala: effects of lesions of the
      posterior intralaminar thalamus on foot-shock-induced c-Fos expression in the
      subdivisions of the lateral amygdala.
AB  - The lateral nucleus of the amygdala (LA) is a site of convergence for auditory
      (conditioned stimulus) and foot-shock (unconditioned stimulus) inputs during fear
      conditioning. The auditory pathways to LA are well characterized, but less is
      known about the pathways through which foot shock is transmitted. Anatomical
      tracing and physiological recording studies suggest that the posterior
      intralaminar thalamic nucleus, which projects to LA, receives both auditory and
      somatosensory inputs. In the present study we examined the expression of the
      immediate-early gene c-fos in the LA in rats in response to foot-shock
      stimulation. We then determined the effects of posterior intralaminar thalamic
      lesions on foot-shock-induced c-Fos expression in the LA. Foot-shock stimulation
      led to an increase in the density of c-Fos-positive cells in all LA subnuclei in
      comparison to controls exposed to the conditioning box but not shocked. However,
      some differences among the dorsolateral, ventrolateral and ventromedial subnuclei
      were observed. The ventrolateral subnucleus showed a homogeneous activation
      throughout its antero-posterior extension. In contrast, only the rostral aspect
      of the ventromedial subnucleus and the central aspect of the dorsolateral
      subnucleus showed a significant increment in c-Fos expression. The density of c
      Fos-labeled cells in all LA subnuclei was also increased in animals placed in the
      box in comparison to untreated animals. Unilateral electrolytic lesions of the
      posterior intralaminar thalamic nucleus and the medial division of the medial
      geniculate body reduced foot-shock-induced c-Fos activation in the LA ipsilateral
      to the lesion. The number of c-Fos labeled cells on the lesioned side was reduced
      to the levels observed in the animals exposed only to the box. These results
      indicate that the LA is involved in processing information about the foot-shock
      unconditioned stimulus and receives this kind of somatosensory information from
      the posterior intralaminar thalamic nucleus and the medial division of the medial
      geniculate body.

PMID- 18620026
TI  - Central administration of corticotropin-releasing factor induces thermogenesis by
      changes in mitochondrial bioenergetics in neonatal chicks.
AB  - Corticotropin-releasing factor (CRF), has multiple biological effects and plays a
      central regulatory role in the hypothalamic-pituitary-adrenal (HPA) axis
      regulating energy homeostasis that is required for adaptive responses to maintain
      and support life. Central administration of CRF increases O(2) consumption, CO(2)
      and heat production resulting in hyperthermia. To determine the precise mechanism
      for this condition, here we investigated transcripts of candidate genes for
      thermogenesis and their up-regulator (avian uncoupling protein (avUCP), avian
      adenine nucleotide translocator (avANT) and avian peroxisome-proliferator
      activated receptor-gamma co-activator-1alpha) and mitochondrial bioenergetics
      (gene transcripts for mitochondrial fatty acid (FA) transport and oxidation
      enzymes; carnitine-palmitoyl-transferase (CPT)-I; CPT-II, long-chain acyl CoA
      dehydrogenase (LCAD), 3-hydroxyacyl CoA dehydrogenase (3HADH) and citrate
      synthase (CS), and enzyme activities of 3HADH and CS) that might explain the
      bioenergetic basis of CRF-induced increased thermogenesis. Neonatal chicks
      (Gallus gallus) with and without i.c.v. injection of CRF (42 pmol) were kept at
      thermoneutral temperature (30 degrees C) for 3 h. Central administration of CRF
      increased the core temperature and plasma NEFA level of chicks compared with the
      control. This CRF-induced increased thermogenesis was not accompanied by
      enhancement of avUCP and/or avANT gene transcripts and was associated with
      increased FA oxidation in tissue specific manner: increase in gene transcript
      levels of CPT-I, CPT-II, LCAD, 3HADH and CS, and increase in enzyme activities of
      3HADH and CS were observed in liver and heart while no such changes were observed
      in skeletal muscle. In conclusion, these results suggest that CRF-induced
      increased thermogenesis in neonatal chicks was not accompanied by enhancement of
      gene transcripts of mitochondrial putative thermogenic proteins, and was induced
      by tissue specific increase in mitochondrial FA transport and beta-oxidation
      enzymes.

PMID- 18620027
TI  - Clusterin expression during fetal and postnatal CNS development in mouse.
AB  - Clusterin (or apolipoprotein J) is a widely distributed multifunctional
      glycoprotein involved in CNS plasticity and post-traumatic remodeling. Using
      biochemical and morphological approaches, we investigated the clusterin ontogeny
      in the CNS of wild-type (WT) mice and explored developmental consequences of
      clusterin gene knock-out in clusterin null (Clu-/-) mice. A punctiform expression
      of clusterin mRNA was detected through the hypothalamic region, neocortex and
      hippocampus at embryonic stages E14/E15. From embryonic stage E16 to the first
      week of the postnatal life, the vast majority of CNS neurons expressed low levels
      of clusterin mRNA. In contrast, a very strong hybridizing signal mainly localized
      in pontobulbar and spinal cord motor nuclei was observed from the end of the
      first postnatal week to adulthood. Astrocytes expressing clusterin mRNA were
      often detected through the hippocampus and neocortex in neonatal mice. Real-time
      polymerase chain amplification and clusterin-immunoreactivity dot-blot analyses
      indicated that clusterin levels paralleled mRNA expression. Comparative analyses
      between WT and Clu-/- mice during postnatal development showed no significant
      differences in brain weight, neuronal, synaptic and astrocyte markers as well
      myelin basic protein expression. However, quantitative estimation of large motor
      neuron populations in the facial nucleus revealed a significant deficit in motor
      cells (-16%) in Clu-/- compared with WT mice. Our data suggest that clusterin
      expression is already present in fetal life mainly in subcortical structures.
      Although the lack of this protein does not significantly alter basic aspects of
      the CNS development, it may have a negative impact on neuronal development in
      certain motor nuclei.

PMID- 18620028
TI  - Motion sickness induced by otolith stimulation is correlated with otolith-induced
      eye movements.
AB  - This article addresses the relationships between motion sickness (MS) and three
      dimensional (3D) ocular responses during otolith stimulation. A group of 19
      healthy subjects was tested for motion sickness during a 16 min otolith
      stimulation induced by off-vertical axis rotation (OVAR) (constant velocity 60
      degrees /s, frequency 0.16 Hz). For each subject, the MS induced during the
      session was quantified, and based on this quantification, the subjects were
      divided into two groups of less susceptible (MS-), and more susceptible (MS+)
      subjects. The angular eye velocity induced by the otolith stimulation was
      analyzed in order to identify a possible correlation between susceptibility to MS
      and 3D eye velocity. The main results show that: (1) MS significantly correlates
      in a multiple regression with several components of the horizontal vestibular eye
      movements i.e. positively with the velocity modulation (P<0.01) and bias (P<0.05)
      of the otolith ocular reflex and negatively with the time constant of the
      vestibulo-ocular reflex (P<0.01) and (2) the length of the resultant 3D eye
      velocity vector is significantly larger in the MS+ as compared with the MS-
      group. Based on these results we suggest that the CNS, including the velocity
      storage mechanism, reconstructs an eye velocity vector modulated by head position
      whose length might predict MS occurrence during OVAR.

PMID- 18620029
TI  - Cellular localization and distribution of dopamine D(4) receptors in the rat
      cerebral cortex and their relationship with the cortical dopaminergic and
      noradrenergic nerve terminal networks.
AB  - The role of the dopamine D(4) receptor in cognitive processes and its association
      with several neuropsychiatric disorders have been related to its preferential
      localization in the cerebral cortex. In the present work we have studied in
      detail the regional and cellular localization of the dopamine D(4) receptor
      immunoreactivity (IR) in the rat cerebral cortex and its relationship to the
      dopaminergic and noradrenergic nerve terminal networks, since both dopamine and
      noradrenaline have a high affinity for this receptor. High levels of D(4) IR were
      found in motor, somatosensory, visual, auditory, temporal association, cingulate,
      retrosplenial and granular insular cortices, whereas agranular insular, piriform,
      perirhinal and entorhinal cortices showed low levels. D(4) IR was present in both
      pyramidal and non-pyramidal like neurons, with the receptor being mainly
      concentrated to layers II/III. Layer I was observed to be exclusively enriched in
      D(4) IR branches of apical dendrites. Finally, mismatches were observed between
      D(4) IR and tyrosine hydroxylase and dopamine beta-hydroxylase IR nerve terminal
      plexuses, indicating that these receptors may be activated at least in part by
      dopamine and noradrenaline operating as volume transmission signals. The present
      findings support a major role of the dopamine D(4) receptor in mediating the
      transmission of cortical dopamine and noradrenaline nerve terminal plexuses.

PMID- 18620030
TI  - Can prepared anticipatory postural adjustments be updated by proprioception?
AB  - Stepping over an obstacle is preceded by a center of pressure (CoP) shift, termed
      anticipatory postural adjustments (APAs). It provides an acceleration of the
      center of mass forward and laterally prior to step initiation. The APAs are
      characterized in the lateral direction by a force exerted by the moving leg onto
      the ground, followed by an unloading of the stepping leg and completed by an
      adjustment corresponding to a slow CoP shift toward the supporting foot. While
      the importance of sensory information in the setting of the APAs is undisputed,
      it is currently unknown whether sensory information can also be used online to
      modify the feedforward command of the APAs. The purpose of this study was to
      investigate how the CNS modulates the APAs when a modification of proprioceptive
      information (Ia) occurs before or during the initiation of the stepping movement.
      We used the vibration of ankle muscles acting in the lateral direction to induce
      modification of the afferent inflow. Subjects learned to step over an obstacle,
      eyes closed, in synchrony to a tone signal. When vibration was applied during the
      initiation of the APAs, no change in the early APAs was observed except in the
      case of a cutaneous stimulation (low frequency vibration); it is thus possible
      that the CNS relies less on proprioceptive information during this early phase.
      Only the final adjustment of the CoP seems to take into account the biased
      proprioceptive information. When vibration was applied well before the APAs
      onset, a postural reaction toward the side of the vibration was produced. When
      subjects voluntarily initiated a step after the postural reaction, the thrust
      amplitude was set according to the direction of the postural reaction. This
      suggests that the planned motor command of the APAs can be updated online before
      they are triggered.

PMID- 18620032
TI  - Kinetics study on a novel natural inhibitor of alpha-chymotrypsin.
AB  - The mechanism of inhibition of alpha-chymotrypsin by benzoylsalireposide (1), a
      phenolic glycoside isolated from Symplocos racemosa, was investigated. Lineweaver
      Burk and Dixon plots and their secondary replots showed that 1 was a non
      competitive inhibitor of this enzyme with the Ki value of 29.60 microM.

PMID- 18620031
TI  - Selective overexpression of excitatory amino acid transporter 2 (EAAT2) in
      astrocytes enhances neuroprotection from moderate but not severe hypoxia
      ischemia.
AB  - Attempts have been made to elevate excitatory amino acid transporter 2 (EAAT2)
      expression in an effort to compensate for loss of function and expression
      associated with disease or pathology. Increased EAAT2 expression has been noted
      following treatment with beta-lactam antibiotics, and during ischemic
      preconditioning (IPC). However, both of these conditions induce multiple changes
      in addition to alterations in EAAT2 expression that could potentially contribute
      to neuroprotection. Therefore, the aim of this study was to selectively
      overexpress EAAT2 in astrocytes and characterize the cell type specific
      contribution of this transporter to neuroprotection. To accomplish this we used a
      recombinant adeno-associated virus vector, AAV1-glial fibrillary acidic protein
      (GFAP)-EAAT2, designed to selectively drive the overexpression of EAAT2 within
      astrocytes. Both viral-mediated gene delivery and beta-lactam antibiotic
      (penicillin-G) treatment of rat hippocampal slice cultures resulted in a
      significant increase in both the expression of EAAT2, and dihydrokainate (DHK)
      sensitive glutamate uptake. Penicillin-G provided significant neuroprotection in
      rat hippocampal slice cultures under conditions of both moderate and severe
      oxygen glucose deprivation (OGD). In contrast, viral-mediated overexpression of
      EAAT2 in astrocytes provided enhanced neuroprotection only following a moderate
      OGD insult. These results indicate that functional EAAT2 can be selectively
      overexpressed in astrocytes, leading to enhanced neuroprotection. However, this
      cell type specific increase in EAAT2 expression offers only limited protection
      compared to treatment with penicillin-G.

PMID- 18620033
TI  - Ocimum basilicum ethanolic extract decreases cholesterol synthesis and lipid
      accumulation in human macrophages.
AB  - Macrophage lipid accumulation induced by low density lipoproteins (LDL) plays a
      pivotal role in atherosclerotic plaque development. Previous work showed that
      Ocimum basilicum extract, used as hypocholesterolemic agent by traditional
      medicine in Morocco, has hypolipidemic activity in rat acute hyperlipimidemia.
      This study investigated the effects of ethanolic extract of O. basilicum on lipid
      accumulation in human macrophages. As modification of LDL increase atherogenicity
      of the particles we evaluated the effects of the extract on LDL oxidation. The
      extract caused a dose-related increase of LDL-resistance to Cu(2+)-induced
      oxidation. Furthermore, at the dose of 60 microg/ml, significantly decreases the
      accumulation of macrophage lipid droplets induced by modified LDL evaluated as by
      red-oil staining. Cholesterol esterification and triacylglycerol synthesis in the
      cells were not affected. Macrophage treatment with 60 microg/ml, but not 20
      microg/ml, of the extract reduced newly synthesized unesterified cholesterol by
      about 60% and decreased scavenger receptors activity by about 20-30%, evaluated
      by the internalization of cholesterol carried by [(3)H]CE-aggregated-LDL. The
      results suggest that O. basilicum ethanolic extract has the capability to reduce
      foam cell formation through the reduction of cholesterol synthesis and the
      modulation of the activity of surface scavenger receptors.

PMID- 18620034
TI  - The origin of nucleus: rebuild from the prokaryotic ancestors of ribosome export
      factors.
AB  - Various hypotheses have been proposed on the evolutionary origin of eukaryotic
      nucleus. Because one of the major cargoes in the nucleocytoplasmic export in the
      eukaryotic cell is the ribosome, its stimulating proteins called Ribosome Export
      Factors (REFs) might have an evolutionary history of inscribing the origin of
      eukaryotic nucleus. With the aim of understanding the evolutionary origin of the
      nucleus, here we employed the yeast REFs and searched for their evolutionary
      origin in more than 500 genomes of archaea and eubacteria by the PSI-BLAST
      search. Our results showed that the non-membranous REFs (non-mREFs) originated
      exclusively from eubacterial proteins, whereas the membranous REFs (mREFs) are
      from both archaeal and eubacterial proteins. Since the non-mREFs just work inside
      the nucleus while the mREFs shuttle between the nucleus and the cytoplasm, these
      results suggest that the extant REFs working inside the nucleus have derived
      exclusively from eubacterial proteins, implying that the nucleus arose in a cell
      that contained chromosomes possessing a substantial fraction of eubacterial
      genes, in line with the predictions of several models entailing endosymbiosis at
      eukaryote origins.

PMID- 18620035
TI  - Replication timing of extremely large genes on human chromosomes 11q and 21q.
AB  - Many human genes have been mapped precisely in the genome. These genes vary from
      a few kb to more than 1 Mb in length. Previously, we measured replication timing
      along the entire lengths of human chromosomes 11q and 21q at the sequence level.
      In the present study, we used the newest information for human chromosomes 11q
      and 21q to analyze the replication timing of 30 extremely large genes (>250 kb)
      in two human cell lines (THP-1 and Jurkat). The timing of replication differed
      between the 5'- and 3'-ends of each of extremely large genes on 11q and 21q, and
      the time interval between their replication varied among genes of different
      lengths. The large genes analyzed here included several tissue-specific genes
      associated with neural diseases and genes encoding cell adhesion molecules: some
      of these genes had different patterns of replication timing between the two cell
      lines. The amyloid precursor protein gene (APP), which is associated with
      familial Alzheimer's disease (AD1), showed the largest difference in timing of
      replication between its 5'- and 3'-ends in relation to gene length of all the
      large genes studied on 11q and 21q. These extremely large genes were concentrated
      in and around genomic regions in which replication timing switches from early to
      late on both 11q and 21q. The differences of replication timing between the 5'-
      and 3'-terminal regions of large genes may be related to the molecular mechanisms
      that underlie tissue-specific expression.

PMID- 18620037
TI  - Frequency modulation facilitates (modal) auditory restoration of a gap.
AB  - In this study we further investigated processes of auditory restoration (AR) in
      recently described stimulus types: the so-called gap-transfer stimulus, the
      shared-gap stimulus and the pseudo-continuous stimulus. The stimuli typically
      consist of two crossing sounds of unequal duration. In the shared-gap and pseudo
      continuous stimuli, the two crossing sounds share a gap (<45 ms) at their
      crossing point. In the gap-transfer stimulus, only the long sound contains a gap
      (100 ms), whereas the short sound is physically continuous. Earlier research has
      shown that in these stimuli the long sound is subject to AR, in spite of the gap
      it contains, whereas the gap is perceived in the short sound. Experiment 1 of the
      present study showed that AR of the stimuli's long sound was facilitated when its
      slope increased from 0 to 1 oct/s. Experiment 2 showed that the effect of slope
      on AR of the long sound also occurred when the slope relationship between the
      long and short sound was fixed. Implications for a tentative sound edge-binding
      explanation of AR as well as alternative explanations for the effect of slope on
      AR are discussed.

PMID- 18620036
TI  - Interaction of dipeptide prodrugs of saquinavir with multidrug resistance protein
      2 (MRP-2): evasion of MRP-2 mediated efflux.
AB  - Saquinavir (SQV), the first protease inhibitor approved by FDA to treat HIV-1
      infection. This drug is a well-known substrate for multidrug resistance protein-2
      (MRP-2). The objective of this study was to investigate whether derivatization of
      SQV to dipeptide prodrugs, valine-valine-saquinavir (Val-Val-SQV) and glycine
      valine-saquinavir (Gly-Val-SQV), targeting peptide transporter can circumvent MRP
      2 mediated efflux. Uptake and transport studies were carried out across MDCKII
      MRP2 cell monolayers to investigate the interaction of SQV and its prodrugs with
      MRP-2. In situ single pass intestinal perfusion experiments in rat jejunum were
      performed to calculate intestinal absorption rate constants and permeabilities of
      SQV, Val-Val-SQV and Gly-Val-SQV. Uptake studies demonstrated that the prodrugs
      have significantly lower interaction with MRP-2 relative to SQV. Transepithelial
      transport of Val-Val-SQV and Gly-Val-SQV across MDCKII-MRP2 cells exhibited an
      enhanced absorptive flux and reduced secretory flux as compared to SQV.
      Intestinal perfusion studies revealed that synthesized prodrugs have higher
      intestinal permeabilities relative to SQV. Enhanced absorption of Val-Val-SQV and
      Gly-Val-SQV relative to SQV can be attributed to their translocation by the
      peptide transporter in the jejunum. In the presence of MK-571, a MRP family
      inhibitor, there was a significant increase in the permeabilities of SQV and Gly
      Val-SQV indicating that these compounds are probably substrates for MRP-2.
      However, there was no change in the permeability of Val-Val-SQV with MK-571
      indicating lack of any interaction of Val-Val-SQV with MRP-2. In conclusion,
      peptide transporter targeted prodrug modification of MRP-2 substrates may lead to
      shielding of these drug molecules from MRP-2 efflux pumps.

PMID- 18620038
TI  - Ethnoveterinary use of southern African plants and scientific evaluation of their
      medicinal properties.
AB  - AIM OF THE STUDY: Livestock keepers in many developing countries with restricted
      access to orthodox veterinary healthcare services commonly use traditional
      remedies to treat their animals when disease is encountered. This review collates
      the documented use of plants in South Africa for healing various ailments in
      domestic animals, and records bioactivity testing that has been carried out on
      these plants. MATERIALS AND METHODS: A literature survey was conducted on the use
      of plants in South African ethnoveterinary medicine (EVM), as well as on
      biological activity investigations relating to their ethnoveterinary use where
      available. RESULTS: The ethnoveterinary application of plants, and results of
      screening studies of EVM plant extracts in various bioassays is presented. For
      diseases such as coughs, wounds, skin diseases, mild diarrhoea and reproductive
      disorders, EVM may be a cheap and easily accessible alternative to expensive
      pharmaceuticals. Studies on biological activity of EVM plants can provide
      indications of promising leads for extracts that can be developed into
      standardized medications to be used on a commercial basis. Isolation studies on
      active plants may yield pure active compounds that could be chemically modified
      to optimize medicinal value and reduce possible toxic effects. CONCLUSION: In
      South Africa, a large proportion of the population relies on traditional remedies
      to treat themselves and their animals for common diseases. Only a small
      percentage of EVM plants have been analysed for biological activity or toxic
      effects, and hence research in this field offers fertile possibilities for future
      investigation.

PMID- 18620039
TI  - Prevention of common neurodegenerative disorders in the elderly.
AB  - Since population aging has become a worldwide phenomenon, the burden of the age
      related neurodegenerative diseases is expected to increase dramatically in both
      developed and developing nations. Alzheimer's disease is the most common
      neurodegenerative disorder among old people. Prevention may represent an ideal
      solution to the challenge posed by this condition. Recent epidemiological studies
      have revealed a number of risk and protective factors that could influence
      occurrence of dementia including Alzheimer type dementia. We propose that an
      active and stimulating lifestyle in late life as well as an optimal control of
      vascular and other chronic diseases both at middle age and late life can be two
      possible intervention strategies to prevent or postpone the onset of dementia,
      and perhaps other neurodegenerative disorders such as Parkinson's disease.

PMID- 18620040
TI  - Interplay between MgtC and PagC in Salmonella enterica serovar Typhimurium.
AB  - In Salmonella enterica serovar Typhimurium, MgtC and PagC are positively
      regulated by the PhoP-PhoQ two-component system, which is activated under
      magnesium deprivation. Both MgtC and PagC are of unknown function but have been
      involved in intramacrophage survival. We have found that the amount of PagC is
      lowered in a DeltamgtC mutant strain grown in magnesium depleted medium. However,
      the effect of MgtC on PagC does not account for the growth defect of a DeltamgtC
      mutant in macrophages since, in contrast to previous reports, our results
      indicate that PagC does not contribute to intramacrophage survival. In addition,
      a pagC null mutant is only poorly attenuated in Nramp1-negative or Nramp1
      positive mice. On the other hand, a mgtC null mutant is significantly more
      attenuated with Nramp1-positive than Nramp1-negative mice, suggesting that a
      functional Nramp1 (Slc11a1) further limits the multiplication of this mutant
      within the host.

PMID- 18620041
TI  - Genomewide comparative phylogenetic and molecular evolutionary analysis of tubby
      like protein family in Arabidopsis, rice, and poplar.
AB  - Tubby-like proteins, which are characterized by a highly conserved tubby domain,
      play an important role in the maintenance and function of neuronal cells during
      postdifferentiation and development in mammals. In additional to the tubby
      domain, most tubby-like proteins in plants also possess an F-box domain. Plants
      also appear to harbor a large number of TLP genes. To gain insight into how TLP
      genes evolved in plants, we conducted a comparative phylogenetic and molecular
      evolutionary analysis of the tubby-like protein gene family in Arabidopsis, rice,
      and poplar. Genomewide screening identified 11 TLP genes in Arabidopsis, 14 in
      rice, and 11 in poplar. Phylogenetic trees, domain organizations, and intron/exon
      structures classified this family into three subfamilies and indicated that
      species-specific expansion contributed to the evolution of this family in plants.
      We determined that in rice and poplar, the tubby-like protein family had expanded
      mainly through segmental duplication events. Tissue-specific expression analysis
      indicated that functional diversification of the duplicated TLP genes was a major
      feature of long-term evolution. Our results also demonstrated that the tubby and
      F-box domains had co-evolved during the evolution of proteins containing both
      domains.

PMID- 18620042
TI  - Evidence that oxidative stress is linked to anxiety-related behaviour in mice.
AB  - Oxidative stress in central and peripheral systems is involved in many diseases,
      including cancer, cardiovascular diseases, neurodegenerative diseases and several
      psychiatric disorders. In the present study, the brain and peripheral oxidative
      status of non-anxious and anxious mice was evaluated using 2',7'
      dichlorofluorescin diacetate (DCFH-DA), a sensor of reactive oxygen species
      (ROS). Here we report that anxiety levels are linked to the oxidative status in
      both neuronal and glial cells in the cerebellum and hippocampus, in neurons of
      the cerebral cortex and in peripheral leucocytes (monocytes, granulocytes and
      lymphocytes), revealing the presence of oxidative stress in the central and
      peripheral systems of anxious mice. These findings suggest the redox system in
      anxious mice may play a role in neuroinflammation and neurodegeneration,
      predisposing them to recurrent infections and chronic inflammation.

PMID- 18620043
TI  - Statistical methods for estimating the probability of spontaneous abortion in
      observational studies--analyzing pregnancies exposed to coumarin derivatives.
AB  - BACKGROUND: Spontaneous abortion rates are of general interest when investigating
      pregnancy outcome. In most studies observations are left truncated as pregnant
      women enter with a delay of several weeks after conception. Apart from
      spontaneous abortion pregnancy may end in induced abortion or live birth. These
      outcomes are considered as competing events (risks). Although statistical methods
      for handling this setting are available since more than 10 years, studies on
      pregnancy outcome after drug exposure usually report crude rates of spontaneous
      abortions, ignoring left truncation and competing risks. METHODS: The authors
      propose simple methods which remove bias inherent to crude rates. The probability
      of spontaneous abortion is estimated using an event-history based approach for
      the subdistribution of competing risks that handles left truncation
      appropriately. Variance estimation enables the construction of approximate
      confidence intervals and of a simple test-statistic for comparing rates between
      different cohorts. The proposed methods are applied to a comparative prospective
      study on the association of spontaneous abortion and exposure to coumarin
      derivatives. RESULTS: The naive analysis using crude rates gives substantially
      different results than those based on the proposed methods, with up to a twofold
      change. Correctly incorporating left truncation into the analysis may increase
      the variance of the estimators, relative to an ideal sample where all pregnancies
      are followed from the time of conception. The consequences of such truncation for
      study design are discussed. CONCLUSION: Combining corrections for left truncation
      and competing risks offers a powerful method for analyzing miscarriage risk.

PMID- 18620044
TI  - The non-provitamin A carotenoid, lutein, inhibits NF-kappaB-dependent gene
      expression through redox-based regulation of the phosphatidylinositol 3
      kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways: role of H(2)O(2) in NF
      kappaB activation.
AB  - Reactive oxygen species (ROS) have been implicated in the regulation of NF-kappaB
      activation, which plays an important role in inflammation and cell survival.
      However, the molecular mechanisms of ROS in NF-kappaB activation remain poorly
      defined. We found that the non-provitamin A carotenoid, lutein, decreased
      intracellular H(2)O(2) accumulation by scavenging superoxide and H(2)O(2) and the
      NF-kappaB-regulated inflammatory genes, iNOS, TNF-alpha, IL-1beta, and
      cyclooxygenase-2, in lipopolysaccharide (LPS)-stimulated macrophages. Lutein
      inhibited LPS-induced NF-kappaB activation, which highly correlated with its
      inhibitory effect on LPS-induced IkappaB kinase (IKK) activation, IkappaB
      degradation, nuclear translocation of NF-kappaB, and binding of NF-kappaB to the
      kappaB motif of the iNOS promoter. This compound inhibited LPS- and H(2)O(2)
      induced increases in phosphatidylinositol 3-kinase (PI3K) activity, PTEN
      inactivation, NF-kappaB-inducing kinase (NIK), and Akt phosphorylation, which are
      all upstream of IKK activation, but did not affect the interaction between Toll
      like receptor 4 and MyD88 and the activation of mitogen-activated protein
      kinases. The NADPH oxidase inhibitor apocynin and gp91(phox) deletion reduced the
      LPS-induced NF-kappaB signaling pathway as lutein did. Moreover, lutein treatment
      and gp91(phox) deletion decreased the expressional levels of the inflammatory
      genes in vivo and protected mice from LPS-induced lethality. Our data suggest
      that H(2)O(2) modulates IKK-dependent NF-kappaB activation by promoting the redox
      sensitive activation of the PI3K/PTEN/Akt and NIK/IKK pathways. These findings
      further provide new insights into the pathophysiological role of intracellular
      H(2)O(2) in the NF-kappaB signal pathway and inflammatory process.

PMID- 18620045
TI  - Redox modulation of long-term potentiation in the hippocampus via regulation of
      the glycogen synthase kinase-3beta pathway.
AB  - Alzheimer disease (AD) is an age-related neurodegenerative disorder. Many
      observations indicate that impaired redox regulation is implicated in AD with
      synaptic failure. The aim of the current investigation was to characterize the
      role of redox-active agents on long-term potentiation (LTP) in the CA1 region of
      rat hippocampal slices and to elucidate the molecular sequence of events leading
      to these changes. The results presented here indicate that the membrane-permeable
      oxidizing agent chloramine-T (CH-T) inhibits the induction of LTP, whereas the
      membrane-permeable reducing agent dithiothreitol (DTT) enhances the induction of
      LTP. In contrast, neither the membrane-impermeable oxidizing agent 5,5'-dithio
      bis-(2-nitrobenzoic acid) (DTNB) nor the membrane-impermeable reducing agent tris
      (2-carboxyethyl) phosphine (TCEP) can affect the induction of LTP. The inhibition
      of LTP by CH-T can be restored by pretreatment with DTT but not with TCEP,
      whereas the enhancement of LTP by DTT can be reversed by pretreatment with CH-T
      but not with DTNB. We also provide evidence that the CH-T-evoked inhibition of
      LTP is mediated via activation of glycogen synthase kinase-3beta (GSK-3beta),
      whereas the DTT-evoked enhancement of LTP is mediated via inactivation of GSK
      3beta. These findings will benefit the understanding of the redox contribution to
      the mechanisms underlying synaptic plasticity and AD pathogenesis.

PMID- 18620046
TI  - Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid
      peroxidation in streptozotocin-induced diabetes.
AB  - Free radical production is implicated in the pathogenesis of diabetes mellitus,
      where several pathways and different mechanisms were suggested in the
      pathophysiology of the complications. In this study, we used electron
      paramagnetic resonance (EPR) spectroscopy combined with in vivo spin-trapping
      techniques to investigate the sources and mechanisms of free radical formation in
      streptozotocin-induced diabetic rats. Free radical production was directly
      detected in the diabetic bile, which correlated with lipid peroxidation in the
      liver and kidney. EPR spectra showed the trapping of a lipid-derived radical.
      Such radicals were demonstrated to be induced by hydroxyl radical through isotope
      labeling experiments. Multiple enzymes and metabolic pathways were examined as
      the potential source of the hydroxyl radicals using specific inhibitors. No
      xanthine oxidase, cytochrome P450s, the Fenton reaction, or macrophage activation
      were required for the production of radical adducts. Interestingly, inducible
      nitric oxide synthase (iNOS) (apparently uncoupled) was identified as the major
      source of radical generation. The specific iNOS inhibitor 1400W as well as L
      arginine pretreatment reduced the EPR signals to baseline levels, implicating
      peroxynitrite as the source of hydroxyl radical production. Applying
      immunological techniques, we localized iNOS overexpression in the liver and
      kidney of diabetic animals, which was closely correlated with the lipid radical
      generation and 4-hydroxynonenal-adducted protein formation, indicating lipid
      peroxidation. In addition, protein tyrosine nitration occurred in the diabetic
      target organs. Taken together, our studies support inducible nitric oxide
      synthase as a significant source of EPR-detectable reactive intermediates, which
      leads to lipid peroxidation and may contribute to disease progression as well.

PMID- 18620047
TI  - A FRET-based method to study protein thiol oxidation in histological
      preparations.
AB  - Cysteine residues in proteins have important biological roles. For example,
      disulfide bonds are important structural elements; additionally, reversible
      oxidation of thiols to disulfides functions as a molecular switch and constitutes
      an early response to oxidative damage. Because organs are heterogeneous
      structures composed of diverse cell types, there is a compelling need for a
      histological approach to investigate thiol oxidation in situ in order to address
      the role of specific cell types in oxidative imbalance. Here we describe a
      fluorescence technique-which can be used in association with standard
      immunological staining procedures-to detect variations in disulfides in
      histological preparations. Moreover, by monitoring the fluorescence resonance
      energy transfer (FRET) between a labeled specific primary antibody and the thiol
      probe described here, this method can detect thiol oxidation in candidate
      proteins of interest. When applied to an animal model of Parkinson's disease, our
      technique demonstrated that thiol oxidation occurs selectively in the
      dopaminergic neurons of the substantia nigra, the same neurons that are lost
      selectively in the disease. In summary, this technique provides a new, powerful
      tool for providing further understanding of oxidative imbalance, a phenomenon
      common to many diseases.

PMID- 18620048
TI  - Viperous fangs: development and evolution of the venom canal.
AB  - Fangs are specialised long teeth that contain either a superficial groove (Gila
      monster, Beaded lizard, some colubrid snakes), along which the venom runs, or an
      enclosed canal (viperid, elapid and atractaspid), down which the venom flows
      inside the tooth. The fangs of viperid snakes are the most effective venom
      delivery structures among vertebrates and have been the focus of scientific
      interests for more than 200 years. Despite this interest the questions of how the
      canal at the centre of the fang forms remains unresolved. Two different
      hypotheses have been suggested. The mainstream hypothesis claims that the venom
      conducting canal develops by the invagination of the epithelial wall of the
      developing tooth germ. The sides of this invagination make contact and finally
      fuse to form the enclosed canal. The second hypothesis, known as the "brick
      chimney", claims the venom-conducting canal develops directly by successive
      dentine deposition as the tooth develops. The fang is thus built up from the tip
      to the base, without any folding of the tooth surface. In an attempt to cast
      further light on this subject the early development of the fangs was followed in
      a pit viper, Trimeresurus albolabris, using the expression of Sonic hedgehog
      (Shh). We demonstrate that the canal is indeed formed by an early folding event,
      resulting from an invagination of epithelial cells into the dental mesenchyme.
      The epithelial cells proliferate to enlarge the canal and then the cells die by
      apoptosis, forming an empty tube through which the poison runs. The entrance and
      discharge orifices at either end of the canal develop by a similar invagination
      but the initial width of the invagination is very different from that in the
      middle of the tooth, and is associated with higher proliferation. The two sides
      of the invaginating epithelium never come into contact, leaving the orifice open.
      The mechanism by which the orifices form can be likened to that observed in
      reptiles with an open groove along their fangs, such as the boomslang. It is thus
      tempting to speculate that the process of orifice formation in viperids
      represents the ancestral pleisomorphic state, and that enclosed canals developed
      by a change in the shape and size of the initial invagination.

PMID- 18620049
TI  - The PAMPA technique as a HTS tool for partition coefficients determination in
      different solvent/water systems.
AB  - 1,2-dichloroethane (DCE) and o-nitrophenyl octyl ether (o-NPOE), were tested for
      their ability to form artificial membranes immobilized on polycarbonate (PC) and
      polyvinylidene fluoride (PVDF) supporting filters using the PAMPA (parallel
      artificial membrane permeability assays) technique. These detailed studies
      provided important information on the application domain of the artificial
      membranes investigated. According to the nature of the organic solvent and the
      composition of the filter, different permeation behaviours were noted. A double
      permeation pathway was observed for DCE-coated with PVDF filters since
      hydrophilic compounds permeated the membrane through aqueous pores created by the
      interaction of DCE and PVDF filters, while the more lipophilic compounds were
      trapped in the DCE present on filters. On the other hand, the permeation through
      PVDF and PC filters coated with o-NPOE did not follow the same mechanisms. An
      interesting application emerged from these mechanistic studies, namely the use of
      PC filters for a first high throughput assay designed to measure o-NPOE/water
      partition coefficients.

PMID- 18620050
TI  - PEGylated chitosan-based polymer micelle as an intracellular delivery carrier for
      anti-tumor targeting therapy.
AB  - Stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles presented a
      potential candidate for intracellular drug delivery carrier due to its special
      spatial structure. In this article, CSO-SA was further modified by polyethylene
      glycol (PEG). The physicochemical properties of PEGylated CSO-SA (PEG-CSO-SA)
      micelles were characterized. After PEGylation, the critical micelle concentration
      (CMC) of PEG-CSO-SA had no significant change; the micelle size increased; and
      the zeta potential decreased. The cellular uptake of CSO-SA micelles before and
      after PEGylation in macrophage RAW264.7, immortalized rat liver cells BRL-3A and
      human liver tumor cells HepG2 was studied. About 58.4+/-0.63% of CSO-SA micelles
      were uptaked by RAW264.7 in 24h, however, only 17.7+/-0.94% of PEG-CSO-SA
      micelles were internalized into RAW264.7 after the CSO-SA was modified with PEG
      in five molar times. Meanwhile, there were no changes in the uptake after
      PEGylation of CSO-SA in BRL-3A and HepG2. Using mitomycin C as a model drug, the
      in vitro anti-tumor activities of the drug loaded in the micelles were
      investigated. The 50% cellular growth inhibition (IC(50)) of the drug decreased
      from 1.97+/-0.2 to 0.13+/-0.02mug/mL after mitomycin C was loaded into CSO-SA
      micelles, and the IC(50) value of the drug had no obvious change when the CSO-SA
      was modified by PEG.

PMID- 18620051
TI  - Contamination of semi-solid dosage forms by leachables from aluminium tubes.
AB  - The objective of this study was to determine to what extent bisphenol A (BPA),
      bisphenol A diglycidyl ether (BADGE) and its derivatives are extractable from
      epoxy-based coatings of aluminium tubes for pharmaceutical use and to monitor
      their leaching into different kinds of semi-solid dosage forms. Migration
      increasing factors should be evaluated. Extraction tests using acetonitrile for
      10 days at 40 degrees C turned out to be suitable to estimate the maximum amount
      of extractables. A plain variability in the nature and amount of extractables
      among tubes of different vendors (n=7) could be demonstrated. Leaching of the
      remnants into various semi-solid drug products (ointment, cream, gel) during
      storage (30 degrees C/40 degrees C) was verifiable. Leachable profiles were,
      apart from storage time and temperature, decisively influenced by the matrix. In
      particular, matrix polarity seemed to play a crucial role. Thus, the highest
      amount of leachables was found in isopropanol-based carbomer gel. Furthermore, in
      use conditions (mechanical stress) enhanced migration significantly. In order to
      ensure quality and safety of semi-solid formulae, interactions between the
      coating material and the drug product should be thoroughly evaluated.

PMID- 18620052
TI  - Optimization of the aerosolization properties of an inhalation dry powder based
      on selection of excipients.
AB  - The aim of this study was to investigate the influence of formulation excipients
      on physical characteristics of inhalation dry powders prepared by spray-drying.
      The excipients used were a series of amino acids (glycine, alanine, leucine,
      isoleucine), trehalose and dipalmitoylphosphatidylcholine (DPPC). The particle
      diameter and the powder density were assessed by laser diffraction and tap
      density measurements, respectively. The aerosol behaviour of the powders was
      studied in a Multi-Stage Liquid Impinger. The nature and the relative proportion
      of the excipients affected the aerosol performance of the powders, mainly by
      altering powder tap density and degree of particle aggregation. The
      alanine/trehalose/DPPC (30/10/60 w/w/w) formulation showed optimal aerodynamic
      behaviour with a mass median aerodynamic diameter of 4.7 microm, an emitted dose
      of 94% and a fine particle fraction of 54% at an airflow rate of 100 L/min using
      a Spinhaler inhaler device. The powder had a tap density of 0.10 g/cm(3). The
      particles were spherical with a granular surface and had a 4 microm volume median
      diameter. In conclusion, optimization of the aerosolization properties of
      inhalation dry powders could be achieved by appropriately selecting the
      composition of the particles.

PMID- 18620053
TI  - Bone sialoprotein-collagen interaction promotes hydroxyapatite nucleation.
AB  - In bone, hydroxyapatite (HA) crystals are deposited onto the type I collagen
      scaffold by a mechanism that has yet to be elucidated. Bone sialoprotein (BSP) is
      an acidic phosphoprotein that is expressed at high levels in mineralized tissues,
      capable of binding type I collagen, and nucleating HA. Both bone-extracted and
      recombinant BSP (rBSP) bind with equal affinity to collagen. The nature of the
      BSP-collagen interaction and its role in HA nucleation are not known. We have
      used a solid-phase binding assay and affinity chromatography to characterize the
      BSP-collagen interaction. rBSP-binding affinities of triple-helical and fibrillar
      type I collagen were similar (K(D) approximately 13 nM), while that of heat
      denatured type I collagen was lower (K(D) approximately 44 nM), indicating the
      importance of triple-helical structure in binding BSP. Pepsin treatment of
      collagen had no effect on rBSP binding, demonstrating that the telopeptides of
      collagen are not involved. The majority of collagen-bound rBSP was eluted by
      acetonitrile, indicating that hydrophobic interactions are principally
      responsible for binding. Using an HA-nucleation assay, it was shown that rBSP is
      ten-fold more potent in reconstituted fibrillar collagen gels than in agarose
      gels. Nucleating potency of a non-collagen-binding, HA-nucleating peptide
      [rBSP(134-206)] showed no difference in the two gel systems. The work here shows
      that optimal binding of rBSP requires collagen to be in a native, triple-helical
      structure, does not require the telopeptides, and is stabilized by hydrophobic
      interactions. Upon binding to collagen, rBSP displays an increase in nucleation
      potency, implying a co-operative effect of BSP and collagen in mineral formation.

PMID- 18620054
TI  - Sloppiness, robustness, and evolvability in systems biology.
AB  - The functioning of many biochemical networks is often robust-remarkably stable
      under changes in external conditions and internal reaction parameters. Much
      recent work on robustness and evolvability has focused on the structure of
      neutral spaces, in which system behavior remains invariant to mutations. Recently
      we have shown that the collective behavior of multiparameter models is most often
      sloppy: insensitive to changes except along a few 'stiff' combinations of
      parameters, with an enormous sloppy neutral subspace. Robustness is often assumed
      to be an emergent evolved property, but the sloppiness natural to biochemical
      networks offers an alternative nonadaptive explanation. Conversely, ideas
      developed to study evolvability in robust systems can be usefully extended to
      characterize sloppy systems.

PMID- 18620055
TI  - Synthesis, biochemical evaluation and rationalisation of the inhibitory activity
      of a range of phenyl alkyl imidazole-based compounds as potent inhibitors of the
      enzyme complex 17alpha-hydroxylase/17,20-lyase (P450(17alpha)).
AB  - The cytochrome P450 enzyme, 17alpha-hydroxylase/17,20-lyase (P450(17alpha)), is a
      potential target in hormone-dependent cancers. We report the synthesis,
      biochemical evaluation and rationalisation of the inhibitory activity of a number
      of azole-based compounds as inhibitors of the two components of P450(17alpha),
      i.e., 17alpha-hydroxylase (17alpha-OHase) and 17,20-lyase (lyase). The results
      suggest that the imidazole-based compounds are highly potent inhibitors of both
      components, with N-7-phenyl heptyl imidazole (21) (IC(50)=0.32 microM against
      17alpha-OHase and IC(50)=0.10 microM against lyase) and N-8-phenyl octyl
      imidazole (23) (IC(50)=0.25 microM against 17alpha-OHase and IC(50)=0.21 microM
      against lyase) being the two most potent compounds within the current study, in
      comparison to ketoconazole (KTZ) (IC(50)=3.76 microM against 17alpha-OHase and
      IC(50)=1.66 microM against lyase). Furthermore, consideration of the inhibitory
      activity against the two components show that the compounds tested are less
      potent towards the 17alpha-OHase component, a desirable property in the
      development of novel inhibitors of P450(17alpha). Structure-activity relationship
      determination of the range of compounds synthesised suggests that logP (log of
      the partition coefficient) is a key physicochemical factor in determining the
      overall inhibitory activity. In an effort to determine the viability of these
      compounds becoming potential drug candidates as well as to show specificity of
      these compounds, we undertook the biochemical evaluation of the synthesised
      compounds against two isozymes of 17beta-hydroxysteroid dehydrogenase [namely
      type 1 (17beta-HSD1) and type 3 (17beta-HSD3)] and 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD). Consideration of the inhibitory activity possessed by
      the compounds considered within the current study against 3beta-HSD, 17beta-HSD1
      and 17beta-HSD3 shows that there is no clear structure-activity relationship and
      that the compounds appear to possess similar inhibitory activity against both
      3beta-HSD and 17beta-HSD3 whilst against 17beta-HSD1, the compounds appear to
      possess poor inhibitory activity at [I]=100 microM. Indeed, two of the most
      potent inhibitors of P450(17alpha), (compounds 21 and 23), were found to possess
      relatively good levels of inhibition against the three enzymes-compound 21 was
      found to possess approximately 32%, approximately 21% and approximately 37%
      inhibition whilst compound 23 was found to possess approximately 38%,
      approximately 30% and approximately 28% inhibition against 3beta-HSD, 17beta-HSD1
      and 17beta-HSD3 respectively. We therefore concluded that the azole-based
      compounds synthesised within the current study are not suitable for further
      consideration as potential drug candidates due to their lack of specificity.

PMID- 18620056
TI  - Synthesis, biochemical evaluation and rationalisation of the inhibitory activity
      of a range of 4-hydroxyphenyl ketones as potent and specific inhibitors of the
      type 3 of 17beta-hydroxysteroid dehydrogenase (17beta-HSD3).
AB  - We report the synthesis and biochemical evaluation of a number of 4-hydroxyphenyl
      ketones as potential inhibitors of the enzyme 17beta-hydroxysteroid dehydrogenase
      (17beta-HSD). In particular, we evaluated compounds against the catalysis of the
      conversion of androstenedione (AD) to testosterone (T) [17beta-HSD type 3 (17beta
      HSD3)], furthermore, in an effort to determine the specificity of our compounds,
      we evaluated the ability of the compounds to inhibit the catalysis of the
      conversion of estrone (E1) to estradiol (E2) [17beta-HSD type 1 (17beta-HSD1)] as
      well as the conversion of dehydroepiandrosterone (DHEA) to AD [by 3beta
      hydroxysteroid dehydrogenase (3beta-HSD)]. The results of our study suggest that
      the synthesised compounds are, in general, able to inhibit 17beta-HSD3 whilst
      being weak inhibitors of 17beta-HSD1. Against 3beta-HSD, we discovered that all
      of the synthesised compounds were weak inhibitors (all were found to possess less
      than 50% inhibition at [I]=500 microM). More specifically, we discovered that 1
      (4-hydroxy-phenyl)-nonan-1-one (15) was the most potent against 17beta-HSD3
      (IC(50)=2.9 microM) whilst possessing poor inhibitory activity against 17beta
      HSD1 ( approximately 36% inhibitory activity against this reaction at [I]=100
      microM) and less than 10% inhibition for the conversion of DHEA to AD. We have
      therefore provided good lead compounds in the design and synthesis of novel non
      steroidal inhibitors of 17beta-HSD3.

PMID- 18620058
TI  - Treatment with pharmacological peroxisome proliferator-activated receptor alpha
      agonist clofibrate increases intestinal carnitine absorption in rats.
AB  - Activation of PPARalpha by clofibrate has recently been shown to cause
      upregulation of the high-affinity carnitine transporter novel organic cation
      transporter (OCTN) 2 in small intestine. This strongly suggests that PPARalpha
      activation in response to clofibrate treatment improves the absorption of
      carnitine from the diet. To test this hypothesis, we performed an experiment with
      rats which were fed diets with or without 5 g clofibrate/kg diet and with or
      without 5 g L-carnitine/kg diet. PPARalpha was significantly activated by
      clofibrate in small intestine as evidenced by increased relative mRNA
      concentrations of the PPARalpha target gene acyl-CoA oxidase (P < 0.05). Relative
      mRNA concentration of OCTN2 in small intestine was significantly increased by
      clofibrate (P < 0.05) but not the carnitine supplementation, whereas relative
      mRNA concentrations of other carnitine transporters (OCTN1, ATB(0+)) in small
      intestine were not influenced by either clofibrate or carnitine. The absorption
      rate of carnitine in small intestine was markedly higher in rats treated with
      clofibrate than in those treated without clofibrate (P < 0.05). In conclusion,
      the present study shows that administration of clofibrate to rats increases
      carnitine absorption in small intestine which is probably due to the observed
      upregulation of OCTN2 mediated by activation of PPARalpha.

PMID- 18620059
TI  - Estradiol facilitates neurite maintenance by a Src/Ras/ERK signalling pathway.
AB  - Different reports suggest the estrogens are involved in neuritic outgrowth,
      maintenance of dendritic morphology and spine formation in the CNS. However, the
      molecular mechanisms regulated by estrogens on neuronal integrity are not fully
      understood. We have addressed the relationship between 17beta-estradiol-dependent
      ERK pathway stimulation and the maintenance of neuritic morphology in cerebellar
      granule cell cultures (CGC). We report that 17beta-estradiol clearly activates
      ERK phosphorylation in CGC cultured in low potassium via ERalpha localized in the
      plasma membrane and without the activation of the insulin-like growth factor-I
      receptor. 17beta-estradiol activates the ERK pathway through Ras-dependent Src
      kinase activity. A concomitant activation of the cAMP-response element-binding
      protein (CREB) is observed. Moreover, we demonstrate that 17beta-estradiol
      mediated ERK activation is involved in the maintenance of neuritic arborisation
      and neuronal morphology in proapoptotic conditions.

PMID- 18620060
TI  - Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation
      of neural progenitors induced by insulin.
AB  - The fate of neural progenitor cells (NPCs) is determined by many extracellular
      cues. Among them, insulin and insulin-like growth factor (IGF) family are found
      to promote the neuronal differentiation of NPCs. Akt activation has been
      indicated to be responsible for the insulin/IGF-I induced neuronal
      differentiation. However, the mechanism by which insulin/IGF-I-PI3K-Akt pathway
      induces neurogenesis of NPCs is not clear. In this study, we have demonstrated
      that mTOR is involved in the insulin-induced neuronal differentiation. Insulin
      induces neurogenesis of NPCs in a dose-dependent manner. Phosphorylated mTOR has
      been up-regulated in a PI3K-Akt dependent manner during NPC differentiation
      induced by insulin. The specific inhibitor of mTOR, rapamycin, can abrogate the
      increase of differentiated neurons stimulated by insulin. In addition, this is
      not the result from the apoptosis of neurons or NPCs. This research has extended
      the understanding of functions of mTOR and the mechanism of NPC differentiation
      regulated by insulin.

PMID- 18620061
TI  - Characterizing proteins and their interactions in cells and tissues using the in
      situ proximity ligation assay.
AB  - The activity of proteins is typically regulated by secondary modifications and by
      interactions with other partners, resulting in the formation of protein complexes
      whose functions depend on the participating proteins. Accordingly, it is of
      central importance to monitor the presence of interaction complexes as well as
      their localization, thus providing information about the types of cells where the
      proteins are located and in what sub-cellular compartment these interactions
      occur. Several methods for visualizing protein interactions in situ have been
      developed during the last decade. These methods in most cases involve genetic
      constructs, and they have been successfully used in assays of living cell
      maintained in tissue culture, but they cannot easily be implemented in studies of
      clinical specimens. For such samples, affinity reagents like antibodies can be
      used to target the interacting proteins. In this review we will describe the in
      situ proximity ligation assays (in situ PLA), a method that is suitable for
      visualizing protein interactions in both tissue sections and in vitro cell lines,
      and we discuss research tasks when this or other method may be selected.

PMID- 18620062
TI  - Expression of the extracellular domain of OB-cadherin as an Fc fusion protein
      using bicistronic retroviral expression vector.
AB  - Osteoblast cadherin (OB-cadherin, also known as cadherin-11) is a Ca(2+)
      dependent homophilic cell adhesion molecule that is expressed mainly in
      osteoblasts. OB-cadherin is expressed in prostate cancer and may be involved in
      the homing of metastatic prostate cancer cells to bone. The extracellular domain
      of OB-cadherin may be used to inhibit the adhesion between prostate cancer cells
      and osteoblasts. In this report, we describe the expression of the extracellular
      domain of OB-cadherin as an Fc fusion protein (OB-CAD-Fc) in human embryonic
      kidney 293FT cells using a bicistronic retroviral vector. Coexpression of GFP and
      OB-CAD-Fc through the bicistronic vector permitted enrichment of OB-CAD-Fc
      expressing cells by fluorescence-activated cell sorting. Recombinant OB-CAD-Fc
      proteins were secreted into cell medium, and about 0.85 mg of purified OB-CAD-Fc
      protein was purified from 1l of the conditioned medium using immobilized protein
      A-affinity chromatography. The purified OB-CAD-Fc was biologically active because
      it supported the adhesion of PC3 cells and L cells transduced with OB-cadherin.
      The availability of OB-CAD-Fc offers opportunities to test whether OB-CAD-Fc can
      be used to inhibit OB-cadherin-mediated prostate cancer bone metastasis in vivo
      or to generate antibodies for inhibiting the adhesion between prostate cancer
      cells and osteoblasts.

PMID- 18620063
TI  - Predicting the recognition of natural scenes from single trial MEG recordings of
      brain activity.
AB  - In our daily life we look at many scenes. Some are rapidly forgotten, but others
      we recognize later. We accurately predicted recognition success with natural
      scene photographs using single trial magnetoencephalography (MEG) measures of
      brain activation. Specifically, we demonstrate that MEG responses in the initial
      600 ms following the onset of scene photographs allow for prediction accuracy
      rates up to 84.1% using linear Support-Vector-Machine classification (lSVM). A
      permutation test confirmed that all lSVM based prediction rates were
      significantly better than "guessing". More generally, we present four approaches
      to analyzing brain function using lSVMs. (1) We show that lSVMs can be used to
      extract spatio-temporal patterns of brain activation from MEG-data. (2) We show
      lSVM classification can demonstrate significant correlations between
      comparatively early and late processes predictive of scene recognition,
      indicating dependencies between these processes over time. (3) We use lSVM
      classification to compare the information content of oscillatory and event
      related MEG-activations and show they contain a similar amount of and largely
      overlapping information. (4) A more detailed analysis of single-trial
      predictiveness of different frequency bands revealed that theta band activity
      around 5 Hz allowed for highest prediction rates, and these rates are
      indistinguishable from those obtained with a full dataset. In sum our results
      clearly demonstrate that lSVMs can reliably predict natural scene recognition
      from single trial MEG-activation measures and can be a useful tool for analyzing
      predictive brain function.

PMID- 18620057
TI  - The immune system and cardiac repair.
AB  - Myocardial infarction is the most common cause of cardiac injury and results in
      acute loss of a large number of myocardial cells. Because the heart has
      negligible regenerative capacity, cardiomyocyte death triggers a reparative
      response that ultimately results in formation of a scar and is associated with
      dilative remodeling of the ventricle. Cardiac injury activates innate immune
      mechanisms initiating an inflammatory reaction. Toll-like receptor-mediated
      pathways, the complement cascade and reactive oxygen generation induce nuclear
      factor (NF)-kappaB activation and upregulate chemokine and cytokine synthesis in
      the infarcted heart. Chemokines stimulate the chemotactic recruitment of
      inflammatory leukocytes into the infarct, while cytokines promote adhesive
      interactions between leukocytes and endothelial cells, resulting in
      transmigration of inflammatory cells into the site of injury. Monocyte subsets
      play distinct roles in phagocytosis of dead cardiomyocytes and in granulation
      tissue formation through the release of growth factors. Clearance of dead cells
      and matrix debris may be essential for resolution of inflammation and transition
      into the reparative phase. Transforming growth factor (TGF)-beta plays a crucial
      role in cardiac repair by suppressing inflammation while promoting myofibroblast
      phenotypic modulation and extracellular matrix deposition. Myofibroblast
      proliferation and angiogenesis result in formation of highly vascularized
      granulation tissue. As the healing infarct matures, fibroblasts become apoptotic
      and a collagen-based matrix is formed, while many infarct neovessels acquire a
      muscular coat and uncoated vessels regress. Timely resolution of the inflammatory
      infiltrate and spatial containment of the inflammatory and reparative response
      into the infarcted area are essential for optimal infarct healing. Targeting
      inflammatory pathways following infarction may reduce cardiomyocyte injury and
      attenuate adverse remodeling. In addition, understanding the role of the immune
      system in cardiac repair is necessary in order to design optimal strategies for
      cardiac regeneration.

PMID- 18620065
TI  - Intelligence and EEG phase reset: a two compartmental model of phase shift and
      lock.
AB  - OBJECTIVES: The purpose of this study was to explore the relationship between EEG
      phase reset and performance on the Wechsler Intelligence test. METHODS: The
      electroencephalogram (EEG) was recorded from 19 scalp locations from 378 subjects
      ranging in age from 5 years to 17.6 years. The Wechsler Intelligence test (WISC
      R) was administered to the same subjects on the same day but not while the EEG
      was recorded. Complex demodulation was used to compute instantaneous EEG phase
      differences between pairs of electrodes and the 1st and 2nd derivatives were used
      to measure phase reset by phase shift duration and phase lock duration. The
      dependent variable was full scale I.Q. and the independent variables were phase
      shift duration (SD) and phase lock duration (LD) with age as a covariate.
      RESULTS: Phase shift duration (40-90 ms) was positively related to intelligence
      (P<.00001) and the phase lock duration (100-800 ms) was negatively related to
      intelligence (P<.00001). Phase reset in short interelectrode distances (6 cm) was
      more highly correlated to I.Q. (P<.0001) than in long distances (>12 cm).
      CONCLUSIONS: The duration of unstable phase dynamics and phase locking represent
      a bounded optimization process, for example, too long a duration of phase locking
      then less flexibility and too short of a phase shift then reduced neural
      resources. A two compartmental model of local field coupling and neuron synchrony
      to a preferred phase was developed to explain the findings.

PMID- 18620064
TI  - The relationship between diffusion tensor imaging and volumetry as measures of
      white matter properties.
AB  - There is still limited knowledge about the relationship between different
      structural brain parameters, despite huge progress in analysis of neuroimaging
      data. The aim of the present study was to test the relationship between
      fractional anisotropy (FA) from diffusion tensor imaging (DTI) and regional white
      matter (WM) volume. As WM volume has been shown to develop until middle age, the
      focus was on changes in WM properties in the age range of 40 to 60 years. 100
      participants were scanned with magnetic resonance imaging (MRI). Each hemisphere
      was parcellated into 35 WM regions, and volume, FA, axial, and radial diffusion
      in each region were calculated. The relationships between age and the regional
      measures of FA and WM volume were tested, and then FA and WM volume were
      correlated, corrected for intracranial volume, age, and sex. WM volume was weakly
      related to age, while FA correlated negatively with age in 26 of 70 regions,
      caused by a mix of reduced axial and increased radial diffusion with age. 23
      relationships between FA and WM volume were found, with seven being positive and
      sixteen negative. The positive correlations were mainly caused by increased
      radial diffusion. It is concluded that FA is more sensitive than volume to
      changes in WM integrity during middle age, and that FA-age correlations probably
      are related to reduced amount of myelin with increasing age. Further, FA and WM
      volume are moderately to weakly related and to a large extent sensitive to
      different characteristics of WM integrity.

PMID- 18620066
TI  - Evaluation of hierarchical Bayesian method through retinotopic brain activities
      reconstruction from fMRI and MEG signals.
AB  - A hierarchical Bayesian method estimated current sources from MEG data,
      incorporating an fMRI constraint as a hierarchical prior whose strength is
      controlled by hyperparameters. A previous study [Sato, M., Yoshioka, T.,
      Kajihara, S., Toyama, K., Goda, N., Doya, K., Kawato, M., 2004. Hierarchical
      Bayesian estimation for MEG inverse problem. Neuroimage 23, 806-826] demonstrated
      that fMRI information improves the localization accuracy for simulated data. The
      goal of the present study is to confirm the usefulness of the hierarchical
      Bayesian method by the real MEG and fMRI experiments using visual stimuli with a
      fan-shaped checkerboard pattern presented in four visual quadrants. The proper
      range of hyperparameters was systematically analyzed using goodness of estimate
      measures for the estimated currents. The robustness with respect to false
      positive activities in the fMRI information was also evaluated by using noisy
      priors constructed by adding artificial noises to real fMRI signals. It was shown
      that with appropriate hyperparameter values, the retinotopic organization and
      temporal dynamics in the early visual area were reconstructed, which were in a
      close correspondence with the known brain imaging and electrophysiology of the
      humans and monkeys. The false-positive effects of the noisy priors were
      suppressed by using appropriate hyperparameter values. The hierarchical Bayesian
      method also was capable of reconstructing retinotopic sequential activation in V1
      with fine spatiotemporal resolution, from MEG data elicited by sequential
      stimulation of the four visual quadrants with the fan-shaped checker board
      pattern at much shorter intervals (150 and 400 ms) than the temporal resolution
      of fMRI. These results indicate the potential capability for the hierarchical
      Bayesian method combining MEG with fMRI to improve the spatiotemporal resolution
      of noninvasive brain activity measurement.

PMID- 18620067
TI  - Early Xanthochorema (Trichoptera, Insecta) radiations in New Caledonia originated
      on ultrabasic rocks.
AB  - The toxic and nutrient poor ultrabasic rock substrate covering one-third of New
      Caledonia greatly influenced on the biogeography and diversity of plants in the
      island. Studies on the effect of ultrabasic substrate on fauna are almost
      entirely absent. In this paper we examine whether the diversification of
      Trichoptera of the New Caledonian endemic genus Xanthochorema Kimmins, 1953 was
      related to the presence of ultrabasic substrate. The analysis is based on data
      from a phylogeny derived from DNA sequences of mitochondrial COX1, COX2 and 16S,
      and nuclear EF1a genes. The study of the relationships between ancestral species
      and substrate was carried out using dispersal-vicariance analysis and tracing the
      history of substrate association with ultrabasic and non-ultrabasic distributions
      representing the terminals in the fully resolved phylogenetic tree. Our results
      show that (1) the ancestor of all Xanthochorema species was present on ultrabasic
      substrate, (2) early speciation events were restricted to ultrabasic substrate,
      (3) younger ancestral species dispersed into non-ultrabasic substrates, and (4)
      late speciation events were restricted to non-ultrabasic substrate. These results
      correspond to the hypothesis that New Caledonia once was more extensively covered
      by ultrabasic rocks than at present.

PMID- 18620068
TI  - Hemocyanin in mollusks--a molecular survey and new data on hemocyanin genes in
      Solenogastres and Caudofoveata.

PMID- 18620069
TI  - The effect of motivation on working memory: an fMRI and SEM study.
AB  - This study investigated the effective connectivity between prefrontal regions of
      human brain supporting motivational influence on working memory. Functional
      magnetic resonance imaging (fMRI) and structural equation modeling (SEM) were
      used to examine the interaction between the lateral orbitofrontal (OFC), medial
      OFC, and dorsolateral prefrontal (DLPFC) regions in the left and right hemisphere
      during performance of the verbal 2-back working memory task under two
      reinforcement conditions. The "low-motivation" condition was not associated with
      monetary reinforcement, while the "high-motivation" condition involved the
      probability of winning a certain amount of money. In the "low-motivation"
      condition, the OFC regions in both hemispheres positively influenced the left
      DLPFC activity. In the "high-motivation" condition, the connectivity in the
      network including the right OFC regions and left DLPFC changed from positive to
      negative, whereas the positive connectivity in the network composed of the left
      OFC and left DLPFC became slightly enhanced compared with the "low-motivation"
      condition. However, only the connection between the right lateral OFC and left
      DLPFC showed a significant condition-dependent change in the strength of
      influence conveyed through the pathway. This change appears to be the functional
      correlate of motivational influence on verbal working memory.

PMID- 18620071
TI  - Ups and downs: the STAT1:STAT3 seesaw of Interferon and gp130 receptor
      signalling.
AB  - Downstream of cytokine or growth factor receptors, STAT3 counteracts inflammation
      and promotes cell survival/proliferation and immune tolerance while STAT1
      inhibits proliferation and favours innate and adaptive immune responses. STAT1
      and STAT3 activation are reciprocally regulated and perturbation in their
      balanced expression or phosphorylation levels may re-direct cytokine/growth
      factor signals from proliferative to apoptotic, or from inflammatory to anti
      inflammatory. Here we review the functional canonical and non-canonical effects
      of STAT1/3 activation and discuss the hypothesis that perturbation of their
      expression and/or activation levels may provide novel therapeutic strategies in
      different clinical settings and particularly in cancer.

PMID- 18620070
TI  - Infant visual habituation.
AB  - The use of visual habituation in the study of infant cognition and learning is
      reviewed. This article traces the history of the technique, underlying theory,
      and procedural variation in its measurement. In addition, we review empirical
      findings with respect to the cognitive processes that presumably contribute to
      habituation, studies of developmental course and long-term prediction, as well as
      recent attempts to address or explain the phenomenon of visual habituation
      through the use of mathematical or quantitative models. The review ends with an
      appeal for a return to the study of habituation per se as a valid measure of
      infant learning, rather than relegating the phenomenon to its use as a technique
      for familiarizing infants in procedures testing for discrimination or
      recognition.

PMID- 18620072
TI  - Associated links among mtDNA glycation, oxidative stress and colony sectorization
      in Metarhizium anisopliae.
AB  - Mycelial colonies of filamentous fungi often deteriorate when maintained on
      artificial media, and this can take the form of sterile sectors. We previously
      established that sectorization by the entomopathogenic fungus Metarhizium
      anisopliae correlates with intracellular accumulation of reactive oxygen species
      (ROS). In this study we demonstrate that: (1) H(2)O(2) increases rates of
      sectorization; (2) a stable strain of M. anisopliae eliminates intracellular ROS
      more rapidly than an unstable strain; (3) mitochondrial DNA from sectors
      undergoes a non-enzymatic glycation of deoxyguanosine that is not shown by
      genomic DNA; (4) the membrane potential of mitochondria in sector cells is
      decreased in comparison to wild type cells indicating loss of function; (5) DNA
      glycation changes the properties of DNA and (6) treating wild type mycelia with
      H(2)O(2) reproduced the glycation pattern shown in sectors. H(2)O(2) also
      reproduced the morphological changes in mitochondria and lipid droplets that
      occur in sector cells. Fungal sectorization thus displays aging related
      developmental impairments resulting from oxidative stress, suggesting a new
      research direction for studies on fungal colony deterioration. Mitochondrial DNA
      has a very high AT bias. We speculate that reducing the consequences of glycation
      could provide an adaptive reason for this.

PMID- 18620073
TI  - Maintaining the silence: reflections on long-term RNAi.
AB  - Since the demonstration of RNA interference (RNAi) in mammalian cells,
      considerable research and financial effort has gone towards implementing RNAi as
      a viable therapeutic platform. RNAi is, without doubt, the most promising
      strategy for the treatment of human genetic disorders. Because many of the
      targets proposed for RNAi therapy require chronic treatment, researchers agree
      that the emphasis must now be placed on the safe and long-term application of
      RNAi drugs to reap the benefits at last.

PMID- 18620074
TI  - Recent advances in the preclinical evaluation of the topical antibacterial agent
      REP8839.
AB  - REP8839 is a synthetic fluorovinylthiophene-containing diaryldiamine that
      inhibits bacterial methionyl tRNA synthetase (MetRS) and is a new chemical entity
      that represents a novel pharmacological class. The compound has potent in vitro
      antibacterial activity against many clinically important Gram-positive bacteria
      including the major skin pathogens Staphylococcus aureus and Streptococcus
      pyogenes. In light of the emergence of methicillin-resistant S. aureus in the
      community and increasing resistance to mupirocin, REP8839 is being evaluated as a
      topical agent for the treatment of superficial skin infections. REP8839 was
      active against resistant phenotypes of S. aureus and can be formulated at high
      concentrations to minimize the development of resistance. A formulation of
      REP8839 has demonstrated efficacy in a porcine partial thickness wound infection
      model against mupirocin-resistant S. aureus.

PMID- 18620075
TI  - Host-parasite interactions: the balance of trade.

PMID- 18620076
TI  - Evidence of anoxia-induced channel arrest in the brain of the goldfish (Carassius
      auratus).
AB  - The common goldfish (Carassius auratus) is extremely anoxia tolerant and here we
      provide evidence that "channel arrest" in the brain of these fish contributes to
      ATP conservation during periods of anoxia. Whole-cell patch-clamp recordings of
      slices taken from the telencephalon indicated that the N-methyl-d-aspartate
      (NMDA) receptor, an ionotropic glutamate receptor and Ca(2+)-channel, underwent a
      40-50% reduction in activity during 40 min of acute anoxia. This is the first
      direct evidence of channel arrest in an anoxia-tolerant fish. Because goldfish
      produce ethanol as a byproduct of anaerobic metabolism we then conducted
      experiments to determine if the observed reduction in NMDA receptor current
      amplitude was due to inhibition by ethanol. NMDA receptor currents were not
      inhibited by ethanol (10 mmol L(-1)), suggesting that channel arrest of the
      receptor involved other mechanisms. Longer-term (48 h) in vivo exposure of
      goldfish to anoxic conditions (less than 1% dissolved O(2)) provided indirect
      evidence that a reduction in Na(+)/K(+)-ATPase activity also contributed to ATP
      conservation in the brain but not the gills. Anoxia under these conditions was
      characterized by a decrease in brain Na(+)/K(+)-ATPase activity of 30-40% by 24
      h. Despite 90% reductions in the rates of ventilation, no change was observed in
      gill Na(+)/K(+)-ATPase activity during the 48-h anoxia exposure, suggesting that
      branchial ion permeability was unaffected. We conclude that rapid "channel
      arrest" of NMDA receptors likely prevents excitotoxicity in the brain of the
      goldfish, and that a more slowly developing decrease in Na(+)/K(+)-ATPase
      activity also contributes to the profound metabolic depression seen in these
      animals during oxygen starvation.

PMID- 18620077
TI  - Probabilistic classifiers and automated cancer registration: an exploratory
      application.
AB  - A test of the performance of two probabilistic classifiers (random forests and
      multinomial logit models) in automatically defining cancer cases has been carried
      out on 5608 subjects, registered by the Venetian Tumour Registry (RTV) during the
      years 1987-1996 and manually checked for possible second cancers that occurred
      during the 1997-1999 period. An eightfold cross-validation was performed to
      estimate the classification error; 63 predictive variables were entered into the
      model fitting. The random forest allows to automatically classify 45% of subjects
      with a classification error lower than 5%, while the corresponding error is 31%
      for the multilogit model. The performance of the former classifier is appealing,
      indicating a potential drop of manually checked cases from 1750 to 960 per
      incidence year with a moderate error rate. This result suggests to refine the
      approach and extend it to other categories of manually treated cases.

PMID- 18620078
TI  - Immunohistochemical analysis of Disc1 expression in the developing and adult
      hippocampus.
AB  - In recent years, Disrupted-In-Schizophrenia 1 (DISC1) has emerged as one of the
      most promising candidate genes whose disruption confers an increased risk for
      schizophrenia. Cell biology studies have implicated DISC1 in key
      neurodevelopmental processes including neurite outgrowth and neuronal migration.
      In situ hybridization analysis has revealed that Disc1 is expressed in the
      hypothalamus, olfactory bulbs, the developing cerebral cortex and the
      hippocampus. The hippocampus is of particular interest because abnormalities in
      hippocampal volume and function have been consistently reported in
      schizophrenics. Moreover, DISC1 mutations have been associated with abnormal
      activation of the hippocampus in humans. Given the involvement of the hippocampus
      in the pathophysiology of schizophrenia, there is an intriguing possibility that
      disruption of DISC1 may increase schizophrenia susceptibility by altering the
      normal development and function of the hippocampus. In order to contribute to our
      understanding of DISC1's role in the hippocampus, we have performed a detailed
      analysis of the Disc1 expression pattern in the mouse hippocampus throughout
      development. We report that Disc1 is expressed throughout the hippocampus during
      embryonic development, with expression becoming increasingly specialized in
      Ammon's horn and dentate gyrus granule cells within the first postnatal week.
      This expression pattern remains consistent into adulthood, with a noted decrease
      in Disc1 expression in the adult CA1. Disc1 is also expressed in proliferating
      cells in the adult subgranular zone, as well as in a subset of GABAergic
      interneurons. Our results are the first report of a detailed immunohistochemical
      analysis of the ontogeny of Disc1 expression within the hippocampus.

PMID- 18620079
TI  - Spatio-temporal expression patterns of anterior Hox genes in Atlantic salmon
      (Salmo salar).
AB  - Hox genes encode transcription factors that play important roles in patterning
      the anterior-posterior (A-P) body axis. In vertebrates, up to 14 Hox genes are
      physically linked in 4-13 chromosomal clusters. Their expression patterns obey
      spatial and temporal collinearity. Genes located at the 3' end of the clusters
      are expressed earlier and more anteriorly than those at the 5' end. To
      investigate how the expression of Hox genes has evolved after very recent (
      approximately 25-100 Mya) and relatively recent ( approximately 320-350 Mya)
      genome duplications, we focused on three paralogous groups of salmon anterior Hox
      genes, in which gene duplicates have been retained. RNA-RNA whole mount in situ
      hybridization with gene-specific probes at early development stages showed
      essentially conserved expression patterns for most genes when compared to mouse
      and zebrafish orthologs. However, changes in spatial expression were observed for
      the ancient fish gene duplicate HoxB3b, while recently duplicated genes showed
      divergence in their expression levels.

PMID- 18620080
TI  - Neuromodulation of hypoglossal motoneurons during sleep.
AB  - Hypoglossal motoneurons are influenced by a variety of neuromodulators, some of
      which change dynamically across sleep-wake states to alter motoneuron
      excitability and responses to pharmacological manipulations. Determining the
      mechanisms underlying the modulation of hypoglossal motoneurons during sleep is
      relevant to understanding the increased upper airway resistance, airflow
      limitation and hypoventilation in normal sleeping individuals, as well as the
      airway obstruction underlying the pathogenesis of obstructive sleep apnea. This
      review summarizes current concepts underlying the neurobiology of sleep and
      arousal states, and so identifies the rationale for focus on particular
      neuromodulators and their effects on hypoglossal motoneurons. Emphasis is placed
      on the control of hypoglossal motoneurons by components of the aminergic arousal
      system, i.e., serotonergic, noradrenergic and histaminergic inputs. The role of
      inhibitory mechanisms at the hypoglossal motor nucleus, including glycine and
      gamma-amino butyric acid, and the mixed excitatory and inhibitory influences of
      acetylcholine are also reviewed. New concepts on the control of hypoglossal
      motoneurons by sedative hypnotics are also discussed.

PMID- 18620081
TI  - Postnatal emergence of synaptic plasticity associated with dynamic adaptation of
      the respiratory motor pattern.
AB  - The shape of the three-phase respiratory motor pattern (inspiration,
      postinspiration, late expiration) is controlled by a central pattern generator
      (CPG) located in the ponto-medullary brainstem. Synaptic interactions between and
      within specific sub-compartments of the CPG are subject of intensive research.
      This review addresses the neural control of postinspiratory activity as the
      essential determinant of inspiratory/expiratory phase duration. The generation of
      the postinspiratory phase depends on synaptic interaction between neurones of the
      nucleus tractus solitarii (NTS), which relay afferent inputs from pulmonary
      stretch receptors, and the pontine Kolliker-Fuse nucleus (KF) as integral parts
      of the CPG. Both regions undergo significant changes during the first three
      postnatal weeks in rodents. Developmental changes in glutamatergic synaptic
      functions and its modulation by brain-derived neurotrophic factor may have
      implications in synaptic plasticity within the NTS/KF axis. We propose that
      dependent on these developmental changes, the CPG becomes permissive for short-
      and long-term plasticity associated with environmental, metabolic and behavioural
      adaptation of the breathing pattern.

PMID- 18620082
TI  - Mass spectrometric proteome analysis suggests anaerobic shift in metabolism of
      Dauer larvae of Caenorhabditis elegans.
AB  - The Dauer larva is a non-feeding alternative larval stage of some nematodes
      specialized for long-term survival and dispersal. In this study we compared
      proteome maps obtained from Dauer larvae with those from the corresponding third
      larval stage (L3) of the feeding life cycle of C. elegans wild-type strain N2. We
      demonstrate at the protein level that altered metabolism may participate in
      longevity determination of Dauers. We detected huge amounts of alcohol
      dehydrogenase (CE12212) and aldehyde dehydrogenase (CE29809) in Dauer animals,
      indicating highly active fermentative pathways. Inorganic pyrophosphatase
      (CE05448) that enables to metabolize pyrophosphate as a high-energy source was
      over-expressed in Dauers. An interesting differentially expressed protein was
      phosphatidylethanolamine-binding protein (CE38516) that was found in high
      abundance in samples from Dauer larvae. Protein synthesis may be lowered in Dauer
      animals by the reduced expression of splicing factor rsp-3 (CE31089) and
      methionyl-tRNA synthase (CE34219). We observed significantly lower amounts of the
      pepsin-like aspartyl protease 1 (CE21681) in non-feeding Dauers, which is in
      agreement with reduced nutrient digestion. Finally, the hypothetical protein
      R08E5.2 (CE33294) was present in high abundance in L3 animals.

PMID- 18620083
TI  - Polycarboxylates enhance beetle antifreeze protein activity.
AB  - Antifreeze proteins (AFPs) lower the noncolligative freezing point of water in
      the presence of ice below the ice melting point. The temperature difference
      between the melting point and the noncolligative freezing point is termed thermal
      hysteresis (TH). The magnitude of the TH depends on the specific activity and the
      concentration of AFP, and the concentration of enhancers in the solution. Known
      enhancers are certain low molecular mass molecules and proteins. Here, we
      investigated a series of polycarboxylates that enhance the TH activity of an AFP
      from the beetle Dendroides canadensis (DAFP) using differential scanning
      calorimetry (DSC). Triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetate, the
      most efficient enhancer identified in this work, can increase the TH of DAFP by
      nearly 1.5 fold over than that of the published best enhancer, citrate. The
      Zn(2+) coordinated carboxylate results in loss of the enhancement ability of the
      carboxylate on antifreeze activity. There is not an additional increase in TH
      when a weaker enhancer is added to a stronger enhancer solution. These
      observations suggest that the more carboxylate groups per enhancer molecule the
      better the efficiency of the enhancer and that the freedom of motion of these
      molecules is necessary for them to serve as enhancers for AFP. The hydroxyl
      groups in the enhancer molecules can also positively affect their TH enhancement
      efficiency, though not as strongly as carboxylate groups. Mechanisms are
      discussed.

PMID- 18620084
TI  - Unraveling the mechanisms of tryptophan fluorescence quenching in the
      triosephosphate isomerase from Giardia lamblia.
AB  - In the native state several proteins exhibit a quenching of fluorescence of their
      tryptophans. We studied triosephosphate isomerase from Giardia lamblia (GlTIM) to
      dissect the mechanisms that account for the quenching of fluorescence of its Trp.
      GlTIM contains four Trp per monomer (Trp75, Trp162, Trp173, and Trp196)
      distributed throughout the 3D structure. The fluorescence of the denatured enzyme
      is 3-fold higher than that of native GlTIM. To ascertain the origin of this
      phenomenon, single and triple mutants of Trp per Phe were made. The intrinsic
      fluorescence was determined, and the data were interpreted on the basis of the
      crystal structure of the enzyme. Our data show that the fluorescence of all Trp
      residues is quenched through two different mechanisms. In one, fluorescence is
      quenched by aromatic-aromatic interactions due to the proximity and orientation
      of the indole groups of Trp196 and Trp162. The magnitude of the quenching of
      fluorescence in Trp162 is higher than in the other three Trp. Fluorescence
      quenching is also due to energy transfer to the charged residues that surround
      Trp 75, 173 and 196. Further analysis of the fluorescence of GlTIM showed that,
      among TIMs from other parasites, Trp at position 12 exhibits rather unique
      properties.

PMID- 18620086
TI  - A pI-based protein fractionation method using solid-state buffers.
AB  - The analysis of very complex proteomes is dependent on efficient fractionation
      methods with low level of carry over from fraction to fraction. Among various
      possibilities the separation by ranges of isoelectric points for further analysis
      appears as attractive, but current methods involving an electrically driven
      migration in the presence of ampholyte carriers are not exempt of technical
      complications. In the present work a new separation concept is described
      involving the use of so-called solid-state buffers, in association with ion
      exchangers, to separate protein categories of different pI ranges with a low
      level of protein overlapping. Resin blends packed in separated columns are used
      under a cascade configuration of increasing or decreasing pH and, once proteins
      of different pI are adsorbed by individual resin blends, the columns are
      dissociated. From each column protein mixtures corresponding to a given pI range
      are collected by competitive desorption with salts so as to be ready for
      proteomic analysis. The process is rapid and does not involve electrical fields
      nor addition of carrier ampholyte material. The presence of potassium chloride
      during the separation prevents protein precipitation at the vicinity of their
      isoelectric points. The fractions thus obtained can be used for two dimensional
      electrophoresis and mass spectrometry analysis after the removal of salts.

PMID- 18620085
TI  - Establishment of a European Network for Urine and Kidney Proteomics.

PMID- 18620087
TI  - The art of microRNA: various strategies leading to gene silencing via an ancient
      pathway.
AB  - MicroRNAs (miRNAs), an endogenous type of small RNAs of approximately 22
      nucleotides (nt), have long resided in the cells of plants and animals including
      humans, constituting an ancient pathway of gene regulation in eukaryotes. They
      have a simple structure in their mature form but carry enormous information that
      may regulate up to 90% of the human transcriptome. Furthermore, the multi-facets
      of a miRNA are tightly associated with diverse cellular proteins that make it
      broadly connected to various physiological and pathological processes. This
      review aims to examine miRNAs briefly from their biogenesis to their general
      functions with an emphasis on working mechanisms in regulation of their target
      mRNAs.

PMID- 18620088
TI  - Calmodulin-dependent kinase 1beta is expressed in the epiphyseal growth plate and
      regulates proliferation of mouse calvarial osteoblasts in vitro.
AB  - The Ca(2+)/Calmodulin-dependent protein kinase (CaMK) family is activated in
      response to elevation of intracellular Ca(2+), and includes CaMK1 (as well as
      CaMK2 and CaMK4), which exists as different isoforms (alpha, beta, gamma and
      delta). CaMK1 is present in several cell types and may be involved in various
      cellular processes, but its role in bone is unknown. In situ hybridization was
      used to determine the spatial and temporal expression of CaMK1beta during
      endochondral bone development in mouse embryos and newborn pups. The cellular and
      subcellular distribution of CaMK1 was assessed by quantitative immunogold
      electron microscopy (EM). The role of CaMK1beta in mouse calvarial osteoblasts
      was investigated by using small interfering RNA (siRNA) to silence its
      expression, while in parallel monitoring cell proliferation and levels of
      skeletogenic transcripts. cRNA in situ hybridization and EM studies show that
      CaMK1beta is mainly located in developing long bones and vertebrae (from ED14.5
      until day 10 after birth), with highest expression in epiphyseal growth plate
      hypertrophic chondrocytes. By RT-PCR, we show that CaMK1beta2 (but not beta1) is
      expressed in mouse hind limbs (in vivo) and mouse calvarial osteoblasts (in
      vitro), and also in primary human articular chondrocyte cultures. Silencing of
      CaMK1beta in mouse calvarial osteoblasts by siRNA significantly decreases
      osteoblast proliferation and c-Fos gene expression (approx. 50%), without
      affecting skeletogenic markers for more differentiated osteoblasts (i.e.
      Cbfa1/Runx2, Osterix (Osx), Osteocalcin (Oc), Alkaline phosphatase (Alp) and
      Osteopontin (Opn)). These results identify CaMK1beta as a novel regulator of
      osteoblast proliferation, via mechanisms that may at least in part involve c-Fos,
      thus implicating CaMK1beta in the regulation of bone and cartilage development.

PMID- 18620089
TI  - Skeletal effects of estrogen and mechanical loading are structurally distinct.
AB  - Estrogen has been suggested to influence skeletal homeostasis by both increasing
      the sensitivity of the feedback control system for skeletal rigidity and acting
      directly on bone surfaces. The objective of the present study was to explore the
      proposed interaction between the skeletal effects of estrogen and locomotion.
      Thirty 3-week-old littermates of female Sprague-Dawley rats were first randomly
      assigned into bilateral sham (E(+)) or ovariectomy (E(-)) surgery after which,
      the left hindlimb each study animal was cast immobilized (L(-)) while the right
      limb served as locomotively loaded control (L(+)), a classic 2x2 factorial study
      design. After 8-week study period, femoral neck, femur midshaft and distal
      metaphysis were analyzed by peripheral quantitative computed tomography (pQCT),
      microcomputed tomography (microCT), and mechanical testing. The loading-induced
      effects were virtually identical in the estrogen-replete (E(+)) and estrogen
      deplete (E(-)) groups (Femoral neck: +78% vs. +69% in the tCSA, +74% vs. +55% in
      the tBMC, -6.0% vs. -7.2% in the tBMD, and +33% vs. +58% in the F(max); Femoral
      midshaft: +6.9% vs. +3.9% in the cCSA, +13% vs. +13% in the tCSA, +23% vs. +16%
      in the cBMC, +5.2% vs. +5.1% in the cBMD, and +8.0% vs. +8.0% in the F(max),
      respectively. All comparisons, NS), challenging the alleged modulatory effect of
      estrogen on skeletal mechanosensitivity. Estrogen did not have an independent
      effect on the periosteal apposition at any of the evaluated bone regions.
      Instead, according to its primary reproductive function, the effects of estrogen
      were restricted to accrual of bone mass only, the stimulus being apparent at the
      endosteal surface of cortex and trabecular structure of the distal metaphysis. In
      conclusion, the present results indicate that that the actions of estrogen and
      loading on bone structure are independent and additive in nature.

PMID- 18620090
TI  - Advances in Cancer Research: Centennial Volume. Introduction.

PMID- 18620091
TI  - Met-related receptor tyrosine kinase Ron in tumor growth and metastasis.
AB  - The Ron receptor is a member of the Met family of cell surface receptor tyrosine
      kinases and is primarily expressed on epithelial cells and macrophages. The
      biological response of Ron is mediated by binding of its ligand, hepatocyte
      growth factor-like protein/macrophage stimulating-protein (HGFL). HGFL is
      primarily synthesized and secreted from hepatocytes as an inactive precursor and
      is activated at the cell surface. Binding of HGFL to Ron activates Ron and leads
      to the induction of a variety of intracellular signaling cascades that leads to
      cellular growth, motility and invasion. Recent studies have documented Ron
      overexpression in a variety of human cancers including breast, colon, liver,
      pancreas, and bladder. Moreover, clinical studies have also shown that Ron
      overexpression is associated with both worse patient outcomes as well as
      metastasis. Forced overexpression of Ron in transgenic mice leads to
      tumorigenesis in both the lung and the mammary gland and is associated with
      metastatic dissemination. While Ron overexpression appears to be a hallmark of
      many human cancers, the mechanisms by which Ron induces tumorigenesis and
      metastasis are still unclear. Several strategies are currently being undertaken
      to inhibit Ron as a potential therapeutic target; current strategies include the
      use of Ron blocking proteins, small interfering RNA (siRNA), monoclonal
      antibodies, and small molecule inhibitors. In total, these data suggest that Ron
      is a critical factor in tumorigenesis and that inhibition of this protein, alone
      or in combination with current therapies, may prove beneficial in the treatment
      of cancer patients.

PMID- 18620093
TI  - Epithelial morphogenesis and intestinal cancer: new insights in signaling
      mechanisms.
AB  - In this review, the major signal transduction pathways that have been shown to
      play an important role in intestinal homeostasis are highlighted. Each of them,
      the Wnt, Notch, Hedgehog, and Bone Morphogenetic Protein, as well as growth
      factor regulated Receptor Tyrosine Kinases are depicted with a special emphasis
      through their involvement in stem cell maintenance and their role in intestinal
      tumorigenesis. Finally, we discuss recent data on the final steps of tumor
      progression, notably the formation of distant metastases. This multistep process
      is highly complex and still far from being understood while being of major
      importance for the survival of patients with digestive cancer.

PMID- 18620094
TI  - Molecular mechanisms and therapeutic development of angiogenesis inhibitors.
AB  - Bevacizumab (Avastin), a vascular endothelial growth factor antagonist, is the
      first approved antiangiogenic drug for the treatment of human cancers.
      Endostatin, a broad-spectrum endogenous angiogenesis inhibitor, has recently been
      approved in China for cancer therapy. Today, hundreds of antiangiogenic molecules
      targeting different signaling pathways are being tested for their anticancer
      efficacies at preclinical and clinical stages. The underlying mechanisms by which
      these antiangiogenic cancer drugs used in combination with chemotherapy confer
      survival advantages for cancer patients are not fully understood. Thus, deeper
      understanding the mechanisms of tumor angiogenesis and actions of these
      therapeutic molecules is crucial for designing more potent anticancer drugs.

PMID- 18620095
TI  - The tumorigenicity of human embryonic stem cells.
AB  - Human embryonic stem cells (HESCs) are the in vitro descendants of the
      pluripotent inner cell mass (ICM) of human blastocyst stage embryos. HESCs can be
      kept undifferentiated in culture or be differentiated to tissues representing all
      three germ layers, both in vivo and in vitro. These properties make HESC-based
      therapy remarkably appealing for the treatment of various disorders. Upon
      transplantation in vivo, undifferentiated HESCs rapidly generate the formation of
      large tumors called teratomas. These are benign masses of haphazardly
      differentiated tissues. Teratomas also appear spontaneously in humans and in
      mice. When they also encompass a core of malignant undifferentiated cells, these
      tumors are defined as teratocarcinomas. These malignant undifferentiated cells
      are termed embryonic carcinoma (EC), and are the malignant counterparts of
      embryonic stem cells. Here we review the history of experimental teratomas and
      teratocarcinomas, from spontaneous teratocarcinomas in mice to induced teratomas
      by HESC transplantation. We then discuss cellular and molecular aspects of the
      tumorigenicity of HESCs. We also describe the utilization of HESC-induced
      teratomas for the modeling of early human embryogenesis and for modeling
      developmental diseases. The problem of HESC-induced teratomas may also impede or
      prevent future HESC-based therapies. We thus conclude with a survey of approaches
      to evade HESC-induced tumor formation.

PMID- 18620096
TI  - Contact interactions between cells that suppress neoplastic development: can they
      also explain metastatic dormancy?
AB  - A comprehensive listing with accompanying discussions is given for established
      cases of interactions between normal and neoplastic cells of the same histotype
      that suppress neoplastic development. General principles that apply to the
      process are: (a) the requirement for a large excess of normal cells in direct
      contact with the neoplastic cells; (b) the effectiveness of suppression decreases
      with the degree of malignant progression of the neoplastic cells; and (c) the
      transformability of normal cells decreases under long-term negative selection,
      which also increases their contact suppression of neoplastic cells. Although
      suppression requires adhesive contact, it does not require gap junction
      communication, and it represents the first line of defense against tumor
      development. In contrast, potentially metastatic cells released from primary
      carcinomas into the circulation are activated to multiply when they form
      heterotypic adhesions with endothelial and parenchymal cells of distant organs.
      The great majority of the disseminated cancer cells (DCCs) fail to develop
      heterotypic cells adhesions in distant organs, and remain metastatically dormant
      as single cells. The lack of growth factors for the DCC in foreign territory also
      contributes to metastatic dormancy. The major insights about suppression of
      neoplastic development by homotypic contact arose from strictly operational
      experiments with living cells in culture. Molecular characterization of the cell
      cell adhesions that underlie neoplastic suppression and metastasis activation has
      had only limited success, probably because of the complex variety of molecules
      involved. Hence, a program is outlined for further operational experiments on
      cell-cell interactions in tumor suppression to deepen our understanding of the
      neoplastic process, and provide possible avenues for its control.

PMID- 18620092
TI  - TAM receptor tyrosine kinases: biologic functions, signaling, and potential
      therapeutic targeting in human cancer.
AB  - Tyro-3, Axl, and Mer constitute the TAM family of receptor tyrosine kinases
      (RTKs) characterized by a conserved sequence within the kinase domain and
      adhesion molecule-like extracellular domains. This small family of RTKs regulates
      an intriguing mix of processes, including cell proliferation/survival, cell
      adhesion and migration, blood clot stabilization, and regulation of inflammatory
      cytokine release. Genetic or experimental alteration of TAM receptor function can
      contribute to a number of disease states, including coagulopathy, autoimmune
      disease, retinitis pigmentosa, and cancer. In this chapter, we first provide a
      comprehensive review of the structure, regulation, biologic functions, and
      downstream signaling pathways of these receptors. In addition, we discuss recent
      evidence which suggests a role for TAM receptors in oncogenic mechanisms as
      family members are overexpressed in a spectrum of human cancers and have
      prognostic significance in some. Possible strategies for targeted inhibition of
      the TAM family in the treatment of human cancer are described. Further research
      will be necessary to evaluate the full clinical implications of TAM family
      expression and activation in cancer.

PMID- 18620097
TI  - Tumor-microenvironment interactions: dangerous liaisons.
AB  - The interaction between microenvironmental components and tumor cells is
      bidirectional. Tumor cells and their products are capable of regulating and
      altering gene expression in nontumor cells residing in or infiltrating into the
      microenvironment and exert selective pressures on such cells, thereby shaping
      their phenotype. Conversely, microenvironmental components regulate gene
      expression in tumor cells thereby directing the tumor into one or several
      possible molecular evolution pathways, some of which may lead to metastasis. This
      review summarizes six instances in which the tumor liaises with different
      components of its microenvironment. These liaisons result, in most cases, in
      enhanced tumor progression. In these cases (responses of tumor and nontumor cells
      to microenvironmental stress, the interaction of the tumor with fibroblasts,
      endothelial cells and macrophages, the formation of the metastatic niche, and the
      interaction of the tumor with immunoglobulins) the tumor, directly or indirectly,
      alters the phenotype of its interaction partners thereby enlisting them to
      promote its progression. Does the tumor need all these pathways to form
      metastasis? Is there a hierarchy of interactions with respect to impact on tumor
      progression? These questions remain open. They may be answered by approaches
      employed in the analysis of hypercomplex systems.

PMID- 18620098
TI  - Percutaneous valve procedures. Foreword.

PMID- 18620099
TI  - Percutaneous valve procedures: an update.
AB  - Valvular heart disease is an important cause of morbidity and mortality. Aortic
      stenosis and mitral regurgitation account for the majority of patients with
      native valve disease. Although surgical treatment provides satisfactory outcome,
      a large proportion of patients do not undergo a surgical intervention, because of
      the high estimated operative risk and multiple comorbidities. Recently, new
      techniques that enable percutaneous treatment of valvular heart disease have been
      developed and their feasibility has been reported in several studies. All
      techniques target a minimal invasive procedure with a low risk of procedure
      related complications. In this article, an overview of the various percutaneous
      procedures for mitral and aortic valve disease is provided. In addition, an
      update on the ongoing trials in percutaneous valve procedures is presented.
      Finally, the role of imaging in performing percutaneous valve procedures will be
      discussed.

PMID- 18620101
TI  - "They diagnosed bad heart": a qualitative exploration of patients' knowledge
      about and experiences with heart failure.
AB  - BACKGROUND: Patient education is central to the management of individuals with
      heart failure; therefore, it is important to know what these patients understand
      and experience both clinically and personally. OBJECTIVES: This study
      qualitatively explored patients' knowledge regarding a heart failure diagnosis,
      their understanding of their cardiac care providers' treatment recommendations,
      and their views concerning the impact of heart failure on their daily lives and
      prognosis. METHODS: A qualitative study was conducted whereby data were collected
      through 25 telephone interviews with adults being followed for heart failure at a
      Veterans Affairs medical center. Subjects were interviewed using semistructured
      open-ended questions. Audiotaped responses were analyzed using grounded theory
      methods. RESULTS: The majority of participants were elderly, male, and white, and
      had New York Heart Association class II disease. Participants without angina
      typically experienced a lengthy and difficult diagnostic delay, with symptoms
      misattributed to comorbid diseases. Most understood the importance of self
      monitoring and adhering to physician recommendations, and their discussions of
      life-changing effects typically focused on loss of physical functioning and
      decreased quality of life. Although participants wanted to know their prognosis,
      most had not received information about it or about advance care planning.
      CONCLUSION: Patients require opportunities for enhanced communication with
      physicians and health care team members during the challenging diagnostic period
      and subsequently need more information about their medical condition and
      prognosis.

PMID- 18620100
TI  - Relationships between fatigue and early postoperative recovery outcomes over time
      in elderly patients undergoing coronary artery bypass graft surgery.
AB  - BACKGROUND: Despite successful coronary artery bypass graft (CABG) surgery, some
      patients continue to experience fatigue after their surgery. OBJECTIVE: The
      purpose of this secondary analysis study was to examine the relationships of
      fatigue and early recovery outcomes (psychosocial and physiologic functioning,
      and physical activity) over time (6 weeks and 3 months) among older adult
      subjects, age 65 years and older, after CABG surgery. Comparison groups were
      those subjects who had fatigue at 3 weeks after surgery and nonfatigued subjects.
      DESIGN: A prospective, comparative design was used for this secondary analysis
      study. SAMPLE: Subjects in this study were drawn from the control group of
      subjects enrolled in the larger parent study. Subjects (N = 119) were
      dichotomized into fatigue (n = 66) and nonfatigued (n = 53) groups on the basis
      of their 3-week self-reports of postoperative fatigue. RESULTS: At 6 weeks after
      surgery, fatigued subjects had significantly (P < .05) more impaired psychosocial
      functioning (role-emotional [t = 1.9], social [t = 2.6], and mental [t = 1.9]
      functioning) on the basis of the Medical Outcome Study Short Form 36. They had
      significantly (P < .005) higher mean hospital anxiety (t = -3.6) and depression
      (t = -2.9) subscale scores, respectively. Anxiety (t = -2.3, P < .05) remained
      significantly (P < .05) impaired at 3 months. At 6 weeks, role physical
      functioning, measured by the Medical Outcome Study Short Form 36, was
      significantly impaired (t = 2.4, P < .01). There were no significant differences
      in physical activity variables as measured by an RT3 accelerometer (Stayhealthy,
      Inc., Monrovia, CA) and self-report diary. CONCLUSIONS: Persistent fatigue can
      hamper early recovery after CABG surgery. Tailored interventions are needed to
      address fatigue management and improve patient outcomes.

PMID- 18620102
TI  - Prehospital transport of patients with acute myocardial infarction: a community
      wide perspective.
AB  - OBJECTIVE: The objectives of this population-based study were to examine the use
      of emergency medical services (EMS) in greater Worcester, Massachusetts,
      residents (2000 census = 478,000) hospitalized with acute myocardial infarction
      (AMI) at all metropolitan Worcester medical centers in four biennial periods
      between 1997 and 2003. A secondary study aim was to describe the demographic and
      clinical characteristics of patients with AMI transported to metropolitan
      Worcester hospitals by EMS, compared with those transported by other means, and
      their hospital outcomes. METHODS: We reviewed the medical records of 3805
      patients hospitalized for confirmed AMI at 11 greater Worcester medical centers
      during 1997, 1999, 2001, and 2003. Information about the use of EMS, patient
      characteristics, and hospital outcomes was obtained through the review of
      hospital charts. RESULTS: A total of 2693 greater Worcester residents with AMI
      (70.8%) were transported to area hospitals by ambulance. Patients transported by
      ambulance were older, were more likely to be women, had a greater prevalence of
      comorbidities, and had a different symptom profile than patients transported by
      other means. Patients arriving at greater Worcester hospitals by ambulance were
      more likely to develop serious clinical complications, including heart failure
      and cardiogenic shock, and die during hospitalization compared with patients not
      transported by EMS. CONCLUSIONS: Our results suggest that the majority of greater
      Worcester residents seeking care for AMI are transported by EMS. Patients
      transported by ambulance differ from patients transported by other means and are
      more likely to experience adverse hospital outcomes. The reasons why patients use
      EMS in the setting of AMI need to be further explored and patients' care-seeking
      behavior enhanced.

PMID- 18620103
TI  - Diagnostic and prognostic impact of brain natriuretic peptide in cardiac and
      noncardiac diseases.
AB  - OBJECTIVE: Cardiac secretion of brain natriuretic peptide (BNP) increases with
      the progression of congestive heart failure (CHF). The plasma measurement of BNP
      emerged recently as a useful, cost-effective biomarker for the diagnosis and
      prognosis of CHF. METHODS: BNP assay is useful for evaluating patients with acute
      dyspnea, because a low level can help rule out CHF in primary care settings and
      reduce the demand for echocardiography. Equally, BNP level can be particularly
      useful in recognizing heart failure in a patient with acute dyspnea and a history
      of chronic obstructive pulmonary disease. RESULTS: However, although the clinical
      use of BNP as a biomarker in CHF is increasing, the specificity of BNP in CHF is
      not strong, suggesting that other mechanisms beyond simple ventricular stretch
      stimulate BNP release. Multiple disorders in the intensive care unit, apart from
      CHF, cause elevated BNP levels, including cardiovascular disease states such as
      ischemia, arrhythmias, cardiac hypertrophy, and coronary endothelial dysfunction,
      as well as disorders of no cardiac origin, such as sepsis, septic shock, and
      acute respiratory distress syndrome. Moreover, the impact of increased BNP in
      patients with sepsis is not clear. The relationship between BNP and both left
      ventricular ejection fraction and left-sided filling pressures is weak, and data
      on the prognostic impact of high BNP levels in patients with sepsis are
      conflicting. CONCLUSION: Nevertheless, this review highlights the potential
      benefits of BNP in the recognition and management of heart failure, and defines
      the gray zones of BNP levels; it also identifies conditions influencing BNP
      levels in relation to a certain heart failure and describes conditions of no
      cardiac origin with increased BNP.

PMID- 18620104
TI  - Comparison of the Short Form 36 and the Hospital Anxiety and Depression Scale
      measuring emotional distress in patients admitted for elective coronary
      angiography.
AB  - BACKGROUND: Anxiety and depression are frequently observed in patients with
      coronary artery disease. Because emotional distress is of prognostic importance
      in these patients, screening is recommended. OBJECTIVE: We compared the Short
      Form 36 (SF-36) and the Hospital Anxiety and Depression Scale (HADS) in measuring
      emotional distress in patients admitted for elective coronary angiography.
      METHODS: A total of 587 patients were consecutively included (mean age 62 years,
      75% were male). Gender-specific partial correlations were calculated for the
      associations between their SF-36 and HADS scores, whereas subgroup differences
      were evaluated using t tests or analysis of variance. RESULTS: In both genders,
      the HADS subscales for anxiety and depression were significantly related to all
      SF-36 subscales and most strongly related to the Mental Health subscale. Both
      HADS and the Mental Health subscale demonstrated a high occurrence of emotional
      distress and discriminated significantly between patients with and without severe
      angina. The HADS, but not the SF-36, demonstrated high levels of emotional
      distress (anxiety) among men without verified coronary artery disease.
      CONCLUSION: Both instruments seem appropriate as screening instruments for
      emotional distress in patients with suspected coronary artery disease. Although
      the Mental Health subscale has the advantage of being shorter, we recommend the
      HADS because it shows anxiety more specifically.

PMID- 18620105
TI  - Repair of acute type A aortic dissection without the use of blood products.
AB  - Ascending aorta replacement for acute aortic dissection repair was carried out in
      a 29-year-old man without the use of blood or blood products. Intraoperative
      blood loss was minimized with the use of biological glues and red cell salvage.
      Erythropoietic agents were started before surgery and continued during and after
      operative repair. Postoperatively, oxygen balance was maintained despite very low
      hemoglobin levels by increasing the cardiac output to compensate for the low
      oxygen-carrying capacity, thus maximizing oxygen delivery. Only essential
      laboratory determinations were carried out, which reduced additional blood loss.
      Repair was successful, and the patient was discharged from the hospital despite a
      delay in diagnosis and definitive surgical repair.

PMID- 18620107
TI  - Streptococcus acidominimus isolated from a multiloculated empyema in a critically
      ill adult man with pneumonia: case report and review of literature.
AB  - We describe a 55-year-old man with a medical history of hypertension and
      schizophrenia who presented to the medical intensive care with delirium and
      respiratory failure requiring intubation. Chest radiography showed a complete
      opacification of the right hemithorax. Subsequent chest computed tomography with
      contrast confirmed a multiloculated right pleural effusion, compressive
      atelectasis, and mediastinal shift to the left. This patient required multiple
      tube thoracostomies and a video-assisted thoracoscopic decortication to
      adequately drain the multiloculated empyemas. Streptococcus acidominimus, a
      common bacterial pathogen in veterinary medicine, was isolated. The organism is
      an uncommon cause of invasive disease in humans. This is the first case report in
      which S. acidominimus was isolated from a multiloculated empyema in a critically
      ill patient causing significant morbidity and must be considered as a potential
      but rare pathogen.

PMID- 18620106
TI  - Electronic feedback messages for home spirometry lung transplant recipients.
AB  - BACKGROUND: Lung transplant recipients use a telemedicine device known as the
      electronic home spirometer to gauge the function of their lungs when they are
      away from the hospital or clinic setting. Health care providers review
      transmitted spirometry tests and user's symptom responses to detect early signs
      of infection and or rejection. Current home spirometry users have questions,
      concerns, and preferences about spirometry that may influence their daily
      adherence. A spirometer with two-way electronic messaging has the capability to
      deliver feedback messages to potentially address these questions and concerns.
      OBJECTIVES: The purpose of this study was to identify the type of messaging
      content users prefer to receive and recognize as positively influencing their
      spirometry use. METHODS: The study design followed a qualitative approach
      investigating the experiences, perceptions, preferences, and realities of home
      spirometry. Three focus group sessions were used to generate opinions and
      interests about automatic messaging content. RESULTS: The focus group approach
      revealed the nature of six categories and five subcategories for feedback
      messaging content. These include education (general, lifestyle, and infection),
      goals, timing, technique, monitoring, and reminders (time sensitive, positive).
      Messages were created according to length, feasibility, past experience, and
      neutrality for electronic implementation. CONCLUSION: The narrative content
      served as the primary source of electronic feedback messages. Actual quotes were
      used when applicable. It is believed that pertinent automated electronic feedback
      messages will enhance home spirometry connection, raise confidence in spirometry
      use, and influence daily adherence to the spirometry protocol. The content also
      serves as a foundation for establishing a plan of care individualized to each
      home spirometry user.

PMID- 18620108
TI  - Severe Legionella pneumonia: rapid presumptive clinical diagnosis with Winthrop
      University Hospital's weighted point score system (modified).
AB  - Legionnaires' disease is a systemic infection involving the lungs and accompanied
      by a characteristic pattern of extrapulmonary organ involvement. Legionnaires'
      disease is one of the non-zoonotic causes of atypical community-acquired
      pneumonia (CAP). Legionnaires' disease commonly presents as severe CAP requiring
      hospitalization and intensive care. Each atypical CAP has its own characteristic
      pattern of extrapulmonary laboratory clinical findings and abnormalities that are
      the basis of clinical syndromic diagnosis. Studies have been unsuccessful in
      identifying individual clinical and laboratory parameters that are specific for
      Legionella. Individually, clinical and laboratory abnormalities lack diagnostic
      specificity. The diagnostic specificity of clinical and laboratory findings is
      increased when combined and are the basis of a clinical syndromic diagnosis. The
      importance of serial nonspecific laboratory abnormalities with Legionnaires'
      disease is emphasized. The sensitivity and specificity of a clinical syndromic
      diagnosis are enhanced if they are based on a weighted point score system. A
      diagnostic weighted point score system is based on the varying diagnostic
      importance of clinical and laboratory diagnostic findings. The Winthrop
      University Hospital's Infectious Disease Division's rapid clinical diagnostic
      weighted point system is based on a weighted point score of clinical and
      laboratory findings. The case presented is that of a 55-year-old man with severe
      CAP who required hospitalization and intensive care admission. The presumptive
      clinical diagnosis of Legionella CAP was based on the Winthrop-University
      Hospital Infectious Disease Division's weighted point score system, which
      permitted early empiric anti-Legionella antimicrobial therapy and prompted
      specific Legionella testing. Legionnaires' disease is definitively diagnosed by
      serology or a urinary Legionella antigen test. This case of severe Legionnaires'
      CAP was confirmed by urinary antigen test reported on hospital day 6. The
      Winthrop-University Hospital is weighted point score system (modified) permits a
      rapid clinical presumptive diagnosis of Legionnaires' disease and is an accurate
      predictor of Legionella CAP.

PMID- 18620109
TI  - The Bix rule.

PMID- 18620110
TI  - Steady as a ROC: the Resuscitation Outcomes Consortium.

PMID- 18620111
TI  - Renal stenting for incidentally discovered renal artery stenosis: is there any
      outcome benefit?
AB  - We evaluated whether there was a clinical outcome benefit in patients
      incidentally discovered to have high-grade renal artery stenosis (RAS) and
      treated with percutaneous transluminal renal angioplasty and stenting (PTRAS) at
      the time of angiogram for another indicated procedure. A retrospective chart
      review was performed on all patients undergoing renal arteriography over 4 years
      at our academic tertiary-care referral center. Review of catheterization reports
      was used to identify patients diagnosed with high-grade RAS (reduction of > or
      =70% luminal diameter by arteriogram). Patients treated with PTRAS were
      identified. Baseline and postprocedure blood pressure (BP, an average of at least
      three independent measurements), glomerular filtration rate, serum creatinine,
      and antihypertensive medication regimen were compared for 12 months of follow-up.
      Over 4 years, 124 patients underwent renal arteriography and 78 (63%) were
      diagnosed with high-grade RAS. Fifty-eight patients (74% of those with high-grade
      RAS) received PTRAS. Patients treated with PTRAS had similar baseline
      characteristics to those with high-grade RAS with no intervention, with the
      exception of lower diastolic BP (DBP; 74 +/- 11.2 vs. 80 +/- 14.2 mm Hg, p =
      0.04) and a higher proportion of hyperlipidemia (78 vs. 55%, p = 0.05). Thirty
      eight out of 58 PTRAS patients (66%) received sufficient follow-up to assess
      outcomes. When baseline and postprocedure variables were compared in PTRAS
      patients with 12-month follow-up, there was a reduction in systolic BP (SBP, 153
      +/- 20.8 vs. 136 +/- 27.2 mm Hg, p = 0.01) and mean arterial pressure (MAP, 103
      +/- 11.2 vs. 95 +/- 14 mm Hg, p = 0.04). When these patients were stratified by
      those with an increase, decrease, or no change in postprocedure antihypertensive
      medications, significant reductions in SBP, MAP, and DBP were noted only in the
      patient population that also had an increase in the number of antihypertensive
      medications. No differences in renal insufficiency were detected. Patients with
      high-grade RAS incidentally discovered during arteriography performed for
      extrarenal disease and treated with PTRAS have a modest reduction in BP, which is
      significant only in those patients with an increased number of antihypertensive
      medications postprocedure. Caution must be taken in stenting patients with
      incidental RAS as outcome benefit may be minimal when compared to medical
      management only.

PMID- 18620112
TI  - Long-term outcomes of endoluminal therapy for chronic atherosclerotic occlusive
      mesenteric disease.
AB  - Percutaneous interventions for symptomatic chronic mesenteric arterial
      atherosclerosis are rapidly gaining popularity. This study evaluates the long
      term anatomic and functional outcomes of endovascular therapy for chronic
      atherosclerotic occlusive mesenteric arterial disease at a tertiary referral
      academic medical center. A retrospective analysis of records from patients who
      underwent endovascular mesenteric arterial interventions between 1984 and 2006
      for chronic mesenteric ischemia was performed. Cases of acute ischemia or cases
      with associated bowel resection were excluded. Results were standardized to
      current Society for Vascular Surgery (SVS) criteria. Kaplan-Meier survival
      analyses were performed to assess time-dependent outcomes. Factor analyses were
      performed using either a multivariate model for fixed variables or a Cox
      proportional hazard model for time-dependent variables. Data are presented as
      mean +/- SEM. Thirty-one patients (84% female, average age 70, range 43-90,
      years) with 41 visceral vessel interventions were identified. Indications for
      intervention included weight loss >10 kg (61%) and/or postprandial pain (94%).
      The median SVS comorbidity score was 15 (range 10-24). All had three-vessel
      athero-occlusive mesenteric disease with a median of two vessels occluded on
      angiography. The median number of vessels revascularized was two. In all cases
      stenosis, and not occlusion, was treated. The 90-day mortality was 20% and the
      major morbidity was 6%. While primary and assisted patency rates for the
      interventions at 7 years were 69 +/- 8% and 72 +/- 9%, respectively (mean +/- SE,
      n > or = 10), cumulative freedom from recurrent symptoms was only 56 +/- 10%.
      Twenty percent of the vessels developed restenosis at a median interval of 0.29
      years (range 0.3-2.8), with a freedom from restenosis of 79 +/- 8% at 5 years.
      Fifty percent of these, all with recurrent symptoms, were reintervened
      successfully with balloon angioplasty and resolution of their symptoms. There was
      no significant difference between the celiac and superior mesenteric artery
      outcomes. The correlation of recurrent symptoms and restenosis was significant (p
      < 0.001). Endoluminal therapy for chronic mesenteric ischemia carries a low
      morbidity and mortality in a high-risk population. While anatomic patency remains
      high, long-term therapeutic benefit is not achieved. In its present iteration,
      endovascular therapy for mesenteric ischemia should be limited to those patients
      without an open surgical option.

PMID- 18620113
TI  - Endovascular treatment of traumatic carotid pseudoaneurysm with stenting and coil
      embolization.
AB  - Posttraumatic internal carotid pseudoaneurysm is an infrequent but potentially
      life-threatening condition that complicates approximately one-third of blunt
      carotid injuries. Other types of injuries include dissection, thrombosis, and
      complete disruption. Historically, carotid pseudoaneurysms have been managed
      operatively with repair, ligation, and anticoagulation, with percutaneous
      angioplasty and stenting emerging over the past decade. We present the case of a
      19-year-old patient with a posttraumatic internal carotid pseudoaneurysm that
      increased in size with conservative management and was treated with coil
      embolization and stenting.

PMID- 18620115
TI  - Too many options for computed tomography for coronary calcium screening: can we
      strike a balance between accuracy and radiation exposure?

PMID- 18620116
TI  - Variability of repeated coronary artery calcium scoring and radiation Dose on 64-
      and 16-slice computed tomography by prospective electrocardiographically
      triggered axial and retrospective electrocardiographically-gated spiral computed
      tomography: a phantom study.
AB  - RATIONALE AND OBJECTIVES: We sought to compare coronary artery calcium (CAC)
      scores, the variability and radiation doses on 64- and 16-slice computed
      tomography (CT) scanners by both prospective electrocardiographically (ECG)
      triggered and retrospective ECG-gated scans. MATERIALS AND METHODS: Coronary
      artery models (n = 3) with different plaque CT densities (approximately 240
      Hounsfield units [HU], approximately 600 HU, and approximately 1000 HU) of four
      sizes (1, 3, 5, and 10 mm in length) on a cardiac phantom were scanned three
      times in five heart rate sequences. The tube current-time products were set to
      almost the same on all four protocols (32.7 mAs for 64-slice prospective and
      retrospective scans, 33.3 mAs for 16-slice prospective and retrospective scans).
      Slice thickness was set to 2.5 mm to keep the radiation dose low. Overlapping
      reconstruction with a 1.25-mm increment was applied on the retrospective ECG
      gated scan. RESULTS: The CAC scores were not different between the four protocols
      (one-factor analysis of variance: Agatston, P = .32; volume, P = .19; and mass, P
      = .09). Two-factor factorial analysis of variance test revealed that the
      interscan variability was different between protocols (P < .01) and scoring
      algorithms (P < .01). The average variability of Agatston/volume/mass scoring and
      effective doses were as follows: 64-slice prospective scan: 16%/15%/11% and 0.5
      mSv; 64-slice retrospective scan: 11%/11%/8% and 3.7 mSv; 16-slice prospective
      scan: 20%/18%/13% and 0.6 mSv; and 16-slice retrospective scan: 16%/15%/11% and
      2.9 to 3.5 mSv (depending on the pitch). CONCLUSION: Retrospective ECG-gated 64
      slice CT showed the lowest variability. Prospective ECG-triggered 64-slice CT,
      with low radiation dose, shows low variability on CAC scoring comparable to
      retrospective ECG-gated 16-slice CT.

PMID- 18620117
TI  - Multiparametric tissue characterization of brain neoplasms and their recurrence
      using pattern classification of MR images.
AB  - RATIONALE AND OBJECTIVES: Treatment of brain neoplasms can greatly benefit from
      better delineation of bulk neoplasm boundary and the extent and degree of more
      subtle neoplastic infiltration. Magnetic resonance imaging (MRI) is the primary
      imaging modality for evaluation before and after therapy, typically combining
      conventional sequences with more advanced techniques such as perfusion-weighted
      imaging and diffusion tensor imaging (DTI). The purpose of this study is to
      quantify the multiparametric imaging profile of neoplasms by integrating
      structural MRI and DTI via statistical image analysis methods to potentially
      capture complex and subtle tissue characteristics that are not obvious from any
      individual image or parameter. MATERIALS AND METHODS: Five structural MRI
      sequences, namely, B0, diffusion-weighted images, fluid-attenuated inversion
      recovery, T1-weighted, and gadolinium-enhanced T1-weighted, and two scalar maps
      computed from DTI (ie, fractional anisotropy and apparent diffusion coefficient)
      are used to create an intensity-based tissue profile. This is incorporated into a
      nonlinear pattern classification technique to create a multiparametric
      probabilistic tissue characterization, which is applied to data from 14 patients
      with newly diagnosed primary high-grade neoplasms who have not received any
      therapy before imaging. RESULTS: Preliminary results demonstrate that this
      multiparametric tissue characterization helps to better differentiate among
      neoplasm, edema, and healthy tissue, and to identify tissue that is likely to
      progress to neoplasm in the future. This has been validated on expert assessed
      tissue. CONCLUSION: This approach has potential applications in treatment, aiding
      computer-assisted surgery by determining the spatial distributions of healthy and
      neoplastic tissue, as well as in identifying tissue that is relatively more prone
      to tumor recurrence.

PMID- 18620118
TI  - Computer-aided detection of ischemic lesions related to subcortical vascular
      dementia on magnetic resonance images.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to develop an automated
      method for detection of the hyperintense ischemic lesions related to subcortical
      vascular dementia based on conventional magnetic resonance images (T1-weighted,
      T2-weighted, and fluid-attenuated inversion-recovery images [FLAIR]). MATERIALS
      AND METHODS: Our proposed method was based on subtraction between the T1-weighted
      image and the FLAIR image. First, a brain region was extracted by an automated
      thresholding technique based on a linear discriminant analysis for a pixel value
      histogram. Next, for enhancement of ischemic lesions, the T1-weighted image was
      subtracted from the fluid-attenuated inversion-recovery image. Ischemic lesion
      candidates were identified using a multiple gray-level thresholding technique and
      a feature-based region-growing technique on the subtraction image. Finally, an
      artificial neural network trained with 15 image features of the ischemic
      candidates was used to remove false-positives. We applied our method to nine
      patients with vascular dementia (age range, 64-94 years, mean age, 69.4 years;
      four males and five females), who were scanned on a 1.5-T magnetic resonance
      unit. RESULTS: Our method achieved a sensitivity of 90% with 4.0 false-positives
      per slice in detection of ischemic lesions. The overlap measure between ischemic
      lesion areas obtained by our method and a neuroradiologist was 60.7% on average.
      The ratio of ischemic lesion area to the whole brain area obtained by our method
      correlated with that determined by a neuroradiologist with a correlation
      coefficient of 0.911. CONCLUSION: Our preliminary results suggest that the
      proposed method may have feasibility for evaluation of the ischemic lesion area
      ratio.

PMID- 18620119
TI  - Contrast-enhanced T1-weighted fluid-attenuated inversion-recovery BLADE magnetic
      resonance imaging of the brain: an alternative to spin-echo technique for
      detection of brain lesions in the unsedated pediatric patient?
AB  - RATIONALE AND OBJECTIVES: We compared contrast-enhanced T1-weighted magnetic
      resonance (MR) imaging of the brain using different types of data acquisition
      techniques: periodically rotated overlapping parallel lines with enhanced
      reconstruction (PROPELLER, BLADE) imaging versus standard k-space sampling
      (conventional spin-echo pulse sequence) in the unsedated pediatric patient with
      focus on artifact reduction, overall image quality, and lesion detectability.
      MATERIALS AND METHODS: Forty-eight pediatric patients (aged 3 months to 18 years)
      were scanned with a clinical 1.5-T whole body MR scanner. Cross-sectional
      contrast-enhanced T1-weighted spin-echo sequence was compared to a T1-weighted
      dark-fluid fluid-attenuated inversion-recovery (FLAIR) BLADE sequence for
      qualitative and quantitative criteria (image artifacts, image quality, lesion
      detectability) by two experienced radiologists. Imaging protocols were matched
      for imaging parameters. Reader agreement was assessed using the exact Bowker
      test. RESULTS: BLADE images showed significantly less pulsation and motion
      artifacts than the standard T1-weighted spin-echo sequence scan. BLADE images
      showed statistically significant lower signal-to-noise ratio but higher contrast
      to-noise ratios with superior gray-white matter contrast. All lesions were
      demonstrated on FLAIR BLADE imaging, and one false-positive lesion was visible in
      spin-echo sequence images. CONCLUSION: BLADE MR imaging at 1.5 T is applicable
      for central nervous system imaging of the unsedated pediatric patient, reduces
      motion and pulsation artifacts, and minimizes the need for sedation or general
      anesthesia without loss of relevant diagnostic information.

PMID- 18620120
TI  - Independent predictors of acute appendicitis on CT with pathologic correlation.
AB  - RATIONALE AND OBJECTIVES: To assess computed tomographic (CT) signs that have
      been described in published studies for the diagnosis of appendicitis to identify
      independent findings that predict appendicitis. METHODS AND MATERIALS: A
      retrospective database search identified 67 patients with a CT scan of the
      abdomen/pelvis and pathologic evaluation of the appendix, including 41 with
      appendicitis and 26 with a normal appendix on pathologic examination. Each
      computed tomogram was re-evaluated by three independent, blinded observers who
      evaluated appendix diameter, enhancement of the appendix, thickening of the
      appendix, presence of an appendicolith, infiltration of peri-appendiceal fat,
      focal cecal thickening, local lymphadenopathy, fluid collections, non-appendiceal
      bowel thickening, non-periappendiceal infiltration of fat, and comparison of peri
      appendiceal fat infiltration to thickening of adjacent bowel loops. RESULTS: Mean
      diameter of the normal appendix (6.7 +/- 2.2 mm) was significantly lower than
      that of the inflamed appendix (12.1 +/- 4.3 mm; P < .001). Significant univariate
      predictors of appendicitis included appendix diameter >8 mm (odds ratio [OR]
      34.8), enhancement of the appendix (OR 4.4), thickening of the appendix (OR 4.3),
      infiltration of peri-appendiceal fat (OR 5.5), focal cecal thickening (OR 5.1),
      non-appendiceal bowel thickening (OR 0.4), and non-periappendiceal infiltration
      of fat (OR = 0.3). Of these variables, only appendix diameter and enhancement of
      the appendix were significant independent predictors of appendicitis on
      multivariate analysis. An overall diagnostic impression based on all secondary
      signs was less accurate than a diagnosis based on appendix diameter alone
      (receiver-operating characteristic analysis: Az = 0.80 vs. Az = 0.91, P = .02).
      Sensitivity/specificity of appendix diameter was 84%/87% using a cutoff between 8
      and 9 mm and 97%/48% using a cutoff between 6 and 7 mm. CONCLUSION: Appendix
      diameter is the best single diagnostic criterion for appendicitis on CT scan. A
      cutoff between 8 and 9 mm provided the best balance of sensitivity/specificity in
      our study population, whereas a cutoff between 6 and 7 mm improved sensitivity at
      the expense of specificity. The presence of appendiceal enhancement provided
      additional diagnostic information, but other secondary signs of appendicitis did
      not improve diagnostic accuracy.

PMID- 18620121
TI  - Classification of parenchymal abnormality in scleroderma lung using a novel
      approach to denoise images collected via a multicenter study.
AB  - RATIONALE AND OBJECTIVES: Computerized classification techniques have been
      developed to offer accurate and robust pattern recognition in interstitial lung
      disease using texture features. However, these techniques still present
      challenges when analyzing computed tomographic (CT) image data from
      multiprotocols because of disparate acquisition protocols or from standardized,
      multicenter clinical trials because of noise variability. Our objective is to
      investigate the utility of denoising thin section CT image data to improve the
      classification of scleroderma disease patterns. The patterns are lung fibrosis
      (LF), groundglass (GG), honeycomb (HC), or normal lung (NL) within small regions
      of interest (ROIs). METHODS: High-resolution CT images were scanned in a
      multicenter clinical trial for the Scleroderma Lung Study. A thoracic radiologist
      contoured a training set (38 patients) consisting of 148 ROIs with 46 LF, 85 GG,
      4 HC, and 13 NL patterns and contoured a test set (33 new patients) consisting of
      132 ROIs with 44 LF, 72 GG, 4 HC, and 12 NL patterns. The corresponding CT slices
      of a contoured ROI were denoised using Aujol's mathematic partial differential
      equation algorithm. The algorithm's noise parameter was estimated as the standard
      deviation of grey-level signal (in Hounsfield units) in a homogeneous, non-lung
      region: the aorta. Within each contoured ROI, every pixel within a 4 x 4
      neighborhood was sampled (4 x 4 grid sampling). All sampled pixels from a
      contoured ROI were assumed to be the same disease pattern as labeled by the
      radiologist. 5,690 pixels (3,009 LF, 1,994 GG, 348 HC, and 339 NL) and 5,045
      pixels (2,665 LF, 1,753 GG, 291 HC, and 336 NL) were sampled in training and test
      sets, respectively. Next, 58 texture features from the original and denoised
      image were calculated for each pixel. Using a multinomial logistic model, subsets
      of features (one from original and another from denoised images) were selected to
      classify disease patterns. Finally, pixels were classified into disease patterns
      using a support vector machine procedure. RESULTS: From the training set,
      multinomial logistic model selected 45 features from the original images and 38
      features from denoised images to classify disease patterns. Using the test set,
      the overall pixel classification rate by SVM increased from 87.8% to 89.5% with
      denoising. The specific classification rates (original/denoised) were 96.3/96.4%
      for LF, 88.8/89.4% for GG, 21.3/28.9% for HC, and 73.5/88.4% for NL. Denoising
      significantly improved the NL and overall classification rates (P = .037 and P =
      .047 respectively) at ROI level. CONCLUSIONS: Analyzing multicenter data using a
      denoising approach led to more parsimonious classification models with increasing
      accuracy. This approach offers a novel alternate classification strategy for
      heterogeneous technical and disease components. Furthermore, the model offers the
      potential to discriminate the multiple patterns of scleroderma disease correctly.

PMID- 18620122
TI  - Computed tomography-navigated transthoracic core biopsy of pulmonary lesions:
      which factors affect diagnostic yield and complication rates?
AB  - RATIONALE AND OBJECTIVES: Only a few studies have systematically evaluated risk
      factors for pneumothorax and pulmonary hemorrhage in computed tomographically
      (CT)-guided transthoracic lung biopsy (TLB). We evaluated the diagnostic yield of
      CT-guided TLB and determined risk factors for pneumothorax and hemorrhage.
      METHODS: One hundred seventy-two CT-guided TLBs were performed on 159 patients
      (mean age 66 +/- 11 years; 72% male) using a 16-gauge core biopsy needle. Lesion
      and patient characteristics, lung function analysis, CT signs of emphysema,
      histopathologic diagnoses, and complications were recorded. Statistical analysis
      was performed with multivariate regression analysis. RESULTS: Histopathologic
      diagnosis was established in 153 cases (89%). Although lesion size was higher (47
      +/- 29 vs. 43 +/- 35 mm, P = .191) and depth was lower (22 +/- 23 vs. 6 +/- 23
      mm, P = .350) in procedures with histopathologic diagnosis, no parameter showed
      significant impact on diagnostic yield. Sensitivity and specificity for detection
      of malignancy were 93% and 100%, respectively, whereas positive and negative
      predictive values were 100% and 88%. Overall accuracy was 95%. Pneumothorax
      occurred in 45 procedures (26%). Hemorrhage was recorded in 17 procedures (10%).
      There was higher frequency of pneumothorax in smaller lesions (35 +/- 23 vs. 50
      +/- 31 mm, P = .003; odds ratio = .96) and greater depth (29 +/- 29 vs. 20 +/- 19
      mm, P = .05; odds ratio = 1.03). CT signs of emphysema revealed higher incidence
      of hemorrhage (35% vs. 23%; P = .04; odds ratio=41.03). Other parameters were
      nonsignificant. CONCLUSIONS: The high diagnostic yield of CT-guided TLB was not
      affected by lesion characteristics or emphysema. Pneumothorax rate was influenced
      by lesion size and depth. Hemorrhage was associated with CT signs of emphysema.

PMID- 18620124
TI  - Development and implementation of a systems-based practice project requirement
      for radiology residents.
AB  - RATIONALE AND OBJECTIVES: Radiology residents must now participate in a learning
      activity that involves identification and analysis of system errors and
      implementation of potential solutions. Evidence of participation must be
      documented in the resident's learning portfolio. MATERIALS AND METHODS: An
      activity based on adult learning principles was designed for residents to
      increase their knowledge of health care systems and problems; gain experience in
      writing a proposal, conducting an investigation, and reporting results; organize
      and present information in a supportive environment; and document participation
      in their portfolio. Postgraduate year 2 residents identify a systems problem. A
      written proposal is required and must include a "plan" that includes a
      hypothesis, a methods section that explains what they will "do" as an
      intervention, a "study" that involves collection and analysis of relevant data,
      and a systems change or "act." Proposals approved by the program director are
      presented to the radiology department. Residents complete projects, evaluate
      their effectiveness, and present their results by spring of postgraduate year 3.
      RESULTS: Goals, objectives, and guidelines were written. Assessment tools were
      identified. From 2006 to 2008, nine projects were proposed and conducted by 12
      residents. Local and national systems issues were selected, and interventions
      involved residents, faculty, and medical students. A timeline was imposed to
      promote sustained effort. CONCLUSION: Opportunities of daily work can be used to
      teach and learn systems-based practice concepts. Residents can use the scientific
      method to test effects of change on health care systems. Relevant and practical
      projects enable residents to learn while improving their clinical and learning
      environments.

PMID- 18620125
TI  - Diagnostic radiology resident compliance with recommended health guidelines:
      effect of resident work environment.
AB  - RATIONALE AND OBJECTIVES: To determine diagnostic radiology resident compliance
      with recommended health guidelines for physical activity, body weight, diet,
      related health indicators, and the effects of the resident work environment on
      compliance. MATERIALS AND METHODS: A request was electronically mailed to members
      of the Association of Program Directors in Radiology and the Association of
      Program Coordinators in Radiology in May 2007 and again in June 2007, asking
      members to forward to their radiology residents an invitation to complete an
      online health survey. Frequency counts and Fisher's exact test, respectively,
      were used to summarize results and to determine statistically significant
      relationships between survey variables. RESULTS: A total of 811 radiology
      residents completed the survey, representing 18% of 4,412 diagnostic radiology
      residents. Five hundred forty-five (67.2%) of 811 were male and 264 (32.6%)
      female. Two hundred ten (25.9%) were first-year, 239 (29.5%) second-year, 201
      (24.8%) third-year, and 161 (19.9%) fourth-year residents. Three hundred two
      (37.2%) engaged in recommended guidelines for physical activity and < or =465
      (57.3%) complied with each of multiple federal dietary guidelines (excluding
      alcohol intake). Up to 329 (40.6%) residents did not know whether they were in
      compliance with various dietary guidelines. A total of 426 (52.5%) residents
      reported working > or =60 hours/week, which significantly correlated with less
      physical activity (P = .013). CONCLUSION: A substantial number of residents are
      out of compliance with federal guidelines for physical activity and diet and are
      not knowledgeable about their personal dietary intake. Long work hours are
      related to a lack of physical activity. Radiology programs may be able to
      influence resident health practices by modifying work hours and the working
      environment, encouraging healthy dietary intake and physical activity, and
      instituting campaigns to inform residents and faculty about health guidelines and
      available wellness programs.

PMID- 18620123
TI  - Registration methodology for histological sections and in vivo imaging of human
      prostate.
AB  - RATIONALE AND OBJECTIVES: Registration enables quantitative spatial correlation
      of features from different imaging modalities. Our objective is to register in
      vivo imaging with histologic sections of the human prostate so that histologic
      truth can be correlated with in vivo imaging features. MATERIALS AND METHODS: In
      vivo imaging of the prostate included T2-weighted anatomic and diffusion weighted
      3-T magnetic resonance imaging (MRI) as well as 11C-choline positron emission
      tomography (PET). In addition, ex vivo 3-T MRI of the prostate specimen,
      histology, and associated block face photos of the prostate specimen were
      obtained. A standard registration method based on mutual information (MI) and
      thin-plate spline (TPS) was applied. Registration among in vivo imaging
      modalities is well established; however, accurate registration involving
      histology is difficult. Our approach breaks up the difficult direct registration
      of histology and in vivo imaging into achievable subregistration tasks involving
      intermediate ex vivo modalities like block face photography and specimen MRI.
      Results of subregistration tasks are combined to compute the intended, final
      registration between in vivo imaging and histology. RESULTS: The methodology was
      applied to two patients and found to be clinically feasible. Overall registered
      anatomic MRI, diffusion MRI, and 11C-choline PET aligned well with histology
      qualitatively for both patients. There is no ground truth of registration
      accuracy as the scans are real patient scans. An indirect validation of the
      registration accuracy has been proposed comparing tumor boundary markings found
      in diffusion MRI and histologic sections. Registration errors for two patients
      between diffusion MRI and histology were 3.74 and 2.26 mm. CONCLUSION: This proof
      of concept paper demonstrates a method based on intrinsic image information
      content for successfully registering in vivo imaging of the human prostate with
      its post-resection histology, which does not require the use of extrinsic
      fiducial markers. The methodology successfully mapped histology onto the in vivo
      imaging space, allowing the observation of how well different in vivo imaging
      features correspond to histologic truth. The methodology is therefore the basis
      for a systematic comparison of in vivo imaging for staging of human prostate
      cancer.

PMID- 18620126
TI  - Assessment of pancreatic tumor resectability with multidetector computed
      tomography: semiautomated console-generated images versus dedicated workstation
      generated images.
AB  - RATIONALE AND OBJECTIVES: The purpose of this retrospective study was to compare
      the maximum intensity projection (MIP) images generated at a multidetector
      computed tomography (MDCT) scanner console using advanced tools at a three
      dimensional (3D) workstation for assessment of pancreatic tumor resectability.
      MATERIALS AND METHODS: Institutional review board approval and informed consent
      wavier were obtained for this retrospective study. The intraoperative findings
      were used as reference standard. Two radiologists assessed console MIPs that were
      created using computed tomographic (CT) data sets of 30 patients (17 men and 13
      women; age range, 35-79 years; mean age, 58 years) operated for pancreatic
      tumors. Semi-automated MIP images were created on a separate MDCT console. Two
      blinded radiologist (R1, R2) and surgeons (S1, S2) evaluated the image data
      independently for vascular involvement and tumor resectability. The image quality
      and diagnostic confidence for MIPs were graded on a 5-point scale (1 = poor, 2 =
      suboptimal, 3 = intermediate, 4 = good; 5 = excellent) and comparison was made
      with 3D workstation image scores. RESULTS: The findings revealed greater than 90%
      sensitivity, specificity, and accuracy for detecting involvement of
      peripancreatic vessels by pancreatic tumor with an excellent interobserver
      agreement (kappa = 0.87-1.00). The findings of console-generated MIPs were same
      as the findings of 3D workstation images. The mean of image quality and
      diagnostic confidence grading for console MIPs by assessors were 4.4 and 4.2,
      respectively. The average time to generate simple MIPs at the console was 3.4
      minutes (range, 2.3-4.4) compared to 26 minutes (range, 18-33) to create images
      at the 3D workstation. CONCLUSION: Semi-automated MIPs generated from an MDCT
      scanner console is an excellent alternative to 3D workstation images for
      assessing resectability of pancreatic tumor based on vascular involvement.
      Console MIPs can be quickly generated during the time of scan and thus can
      improve CT workflow.

PMID- 18620127
TI  - Development of variable pitch factor scanning for multislice computed tomography.
AB  - RATIONALE AND OBJECTIVES: The latest multislice computed tomography (MSCT)
      scanners permit the chest and abdomen to be scanned continuously. However,
      conventionally, it has been necessary to perform scanning twice using different
      pitch factors for the cardiac and abdominal regions. We have developed a new
      scanning technique known as variable pitch factor scanning, in which the table
      speed is changed during scanning to obtain continuous images from the heart to
      the abdomen in a single scan, and have evaluated its physical characteristics.
      MATERIALS AND METHODS: A bead phantom, a comb phantom, and a gold wire placed at
      an angle were scanned using a 64-row MSCT scanner. The variation in the spatial
      resolution and continuity of images in the body axis direction because of changes
      in the pitch factor were evaluated. RESULTS: Because reconstruction taking the
      cone angle into consideration was employed, the spatial resolution in the body
      axis direction was unchanged and the continuity of images in the body axis
      direction was maintained at a certain level even when the pitch factor was
      changed. CONCLUSION: Variable pitch factor scanning is a useful technique for
      obtaining continuous images from the heart to the abdomen in a single scan.

PMID- 18620128
TI  - Three-dimensional mapping of gallbladder wall thickness on computed tomography
      using Laplace's equation.
AB  - RATIONALE AND OBJECTIVES: Traditionally, maximum gallbladder wall thickness is
      measured at a single point on ultrasonography. The purpose of this work was to
      develop an automated technique to measure the thickness of the gallbladder wall
      over the entire gallbladder surface using computer tomography (CT). MATERIALS AND
      METHODS: Subjects who had (5-mm) thick and thin (2.5-mm) reconstruction through
      the abdomen were selected from a research database. Their volumetric computed
      tomographic images were acquired using a multidetector GE Medical Systems
      LightSpeed 16 scanner at 120 kVp, approximately 250 mAs, with standard filter
      reconstruction algorithm and segmented in three dimensions. Two segmentation
      boundaries were obtained, an inner and an outer boundary of the gallbladder wall.
      The thickness of the wall was quantified by computing the distance between the
      boundaries over the entire volume using Laplace's equation from mathematical
      physics. The distance between the surfaces is found by computing normalized
      gradients that form a vector field, representing tangent vectors along field
      lines connecting both boundaries. The Laplacian technique was compared with the
      well-known Euclidean distance transformation (EDT) technique that provides a
      three-dimensional Euclidean distance mapping between the two extracted surfaces.
      RESULTS: The technique was tested on 10 subjects who had thin- and thick-section
      computed tomographic datasets reconstructed from a single scan. The mean
      thickness for the thick- and thin-section CT using Laplace was 3.18 and 2.93 mm,
      respectively. The smooth transition between surfaces resulting from the Laplace
      technique resulted in a coefficient of variation that was less than 1% compared
      to EDT. CONCLUSIONS: EDT technique is very sensitive to imperfect segmentations,
      resulting in higher variation compared to the Laplacian technique. The smooth
      transition between surfaces makes the Laplacian technique more robust compared to
      EDT for the measurement of CT gallbladder thickness.

PMID- 18620129
TI  - Make a stink.

PMID- 18620130
TI  - The electronic era.

PMID- 18620131
TI  - Atopic dermatitis.

PMID- 18620132
TI  - The epidermal barrier in atopic dermatitis.
AB  - Epidermal barrier function is abnormal in individuals with atopic dermatitis
      (AD). It is controversial whether primary epidermal barrier abnormalities alone
      account for the physiological and clinical abnormalities found in those persons
      with AD or whether the observed barrier dysfunction is a consequence of primary
      immunologic abnormalities. Recent evidence is strengthening the argument for the
      former hypothesis. Attention to epidermal barrier care (ie, gentle skin care) has
      long been an important part of the therapy of AD. Advances in our understanding
      of the biology of the epidermal barrier and how this relates to the clinical
      manifestations of this disease has important consequences for new therapeutic
      approaches in the management of AD.

PMID- 18620133
TI  - A multidisciplinary approach to evaluation and treatment of atopic dermatitis.
AB  - Atopic dermatitis is a common, complex disease that frequently follows a chronic,
      relapsing course. The disease can impact the quality of life (QOL) of patients
      and families to a significant degree. Patients and caregivers may focus on
      unproven triggers at the expense of proper skin care. A multidisciplinary
      approach is needed to comprehensively evaluate triggers and response to
      treatment, address confounding factors including sleep disruption, and educate
      patients and caregivers.

PMID- 18620134
TI  - Atopic eczema and the filaggrin story.
AB  - The discovery that null mutations in the filaggrin gene (FLG) are associated with
      atopic eczema represents the single most significant breakthrough in
      understanding the genetic basis of this complex disorder. The association has
      been replicated in multiple independent studies during the past 2 years with the
      use of various methodologies, from populations in Europe, the United States, and
      Japan. Filaggrin plays a key role in epidermal barrier function, and its
      association with atopic eczema emphasizes the importance of barrier dysfunction
      in eczema pathogenesis. This review aims to summarize the current state of
      knowledge regarding the role of FLG mutations in ichthyosis vulgaris, atopic
      eczema, and other skin disorders, with an emphasis on potential clinical
      applications. Further research is needed to clarify the precise role of filaggrin
      in skin and systemic atopic disease, to pave the way for novel therapeutic
      interventions.

PMID- 18620135
TI  - The immune system and atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex
      pathogenesis. It is clinically well-defined and represents one manifestation of
      the atopic state, along with asthma, food allergy and/or allergic rhinitis.
      Within the last several decades, there has been much evidence to support the
      contribution of immune mechanisms in the pathogenesis of AD. It has also been
      documented that the prevalence of all atopic disease, including AD, has been
      increasing, although the environmental factors that may be contributing to this
      increase are not clearly defined. A better understanding of the underlying
      immunopathogenesis of AD should aid in better clinical management and development
      of new treatment options.

PMID- 18620137
TI  - Atopic dermatitis: systemic immunosuppressive therapy.
AB  - Atopic dermatitis (AD) is a pruritic, relapsing skin disorder that negatively
      impacts the quality of life of those affected and that of their families.
      Treatment options for AD encompass a variety of emollients, topical
      corticosteroids, topical immunomodulators, phototherapy, and systemic agents.
      Such agents as systemic corticosteroids, cyclosporine, azathioprine, interferon
      gamma, methotrexate, and mycophenolate mofetil have been shown to be efficacious
      in the treatment of moderate-to-severe AD but are not officially approved for
      this purpose. In this article, we review some of the data supporting efficacy of
      these medications and discuss some of the adverse events associated with their
      use.

PMID- 18620138
TI  - Pediatric atopic dermatitis: the importance of food allergens.
AB  - Food allergy and atopic dermatitis often occur in the same patients. Food-induced
      eczema may be perceived as a controversial topic because the immunologic
      mechanisms have yet to be fully elucidated. Nevertheless, published clinical
      studies have clearly demonstrated that foods can induce symptoms in a subset of
      patients with atopic dermatitis. Those at greatest risk are young children in
      whom eczematous lesions are severe or recalcitrant to therapy. Allergy testing
      can be helpful but must be applied judiciously. A medical history obtained by a
      skilled and knowledgeable health care provider is of paramount importance to
      interpret test results appropriately. Finally, the implementation of proper
      dietary avoidance can improve symptoms and provide safety from potentially fatal
      anaphylaxis. However, if inappropriate prescribed, elimination diets can have
      significant negative nutritional and social consequences.

PMID- 18620139
TI  - Topical therapy in pediatric atopic dermatitis.
AB  - With a prevalence of 10% to 20% in the first decade of life, atopic dermatitis
      (AD) is one of the most common skin disorders in young children. It is a chronic
      illness with limited therapeutic options. Topical anti-inflammatory agents remain
      at the core of medical management; however, their efficacy must be balanced with
      safety concerns, especially as they relate to the pediatric population. This
      article discusses the principles of topical AD therapy with a detailed review of
      the differences between topical corticosteroids and topical calcineurin
      inhibitors. It also includes specialized topical treatment strategies for AD,
      such as wet wraps and diluted bleach baths, and highlights the most common
      challenges to patient compliance in atopic dermatitis.

PMID- 18620136
TI  - Antimicrobial peptides, skin infections, and atopic dermatitis.
AB  - The innate immune system evolved more than 2 billion years ago to first recognize
      pathogens then eradicate them. Several distinct defects in this ancient but
      rapidly responsive element of human immune defense account for the increased
      incidence of skin infections in atopics. These defects include abnormalities in
      the physical barrier of the epidermis, alterations in microbial pattern
      recognition receptors such as toll receptors and nucleotide binding
      oligomerization domains, and a diminished capacity to increase the expression of
      antimicrobial peptides during inflammation. Several antimicrobial peptides are
      affected including; cathelicidin, HBD-2, and HBD-3, which are lower in lesional
      skin of atopics compared with other inflammatory skin diseases, and dermcidin,
      which is decreased in sweat. Other defects in the immune defense barrier of
      atopics include a relative deficiency in plasmacytoid dendritic cells. In the
      future, understanding the cause of these defects may allow therapeutic
      intervention to reduce the incidence of infection in atopic individuals and
      potentially decrease the severity of this disorder.

PMID- 18620140
TI  - Absence of transcriptase activity or transcription-inhibiting ability in
      defective interfering particles of vesicular stomatitis virus.
AB  - Defective interfering particles of New Jersey serotype VSV were found to contain
      very little or no virion transcriptase activity. Furthermore no VSV transcriptase
      activity was observed in cells treated with cycloheximide and infected with DI.
      Cells infected with DI together with standard infectious virus and cycloheximide
      showed little or no DI interference with standard virion primary transcription,
      whereas double infection in the absence of cycloheximide exhibited strong DI
      interference with replication of standard virus genome RNA. We present a model of
      DI interference based upon competition at the level of viral RNA replication.

PMID- 18620141
TI  - Cellular localization and proposed function of midgut trehalase in the silkworm
      larva, Bombyx mori.
AB  - A sorbitol density gradient analysis with the aid of several marker enzymes
      demonstrated that midgut trehalase of the silkworm larvae. Bombyx mori, was
      localized in the microsomal membranes, but not in mitochondria, lysosomes and
      microvilli at the apical surface. Electron microscopic examination showed that
      trehalase-enriched membrane fraction consisted of heterogeneous mixtures of
      membrane vesicles derived from the endoplasmic reticulum and plasma membrane
      parts other than the microvillus membrane. The enzyme-histochemical stains of
      trehalase activity on the midgut section could be detected only at the basal
      surface of the epithelium against haemocoel. Such a specific localization was
      further confirmed by immunohistochemistry with the peroxidase-conjugated antibody
      technique. Thus, it is concluded that midgut trehalase of silkworm larvae is
      situated on the plasma membrane at the basal surface of the epithelium. An intact
      preparation of midgut incubated in vitro in the medium containing
      [(14)C]trehalose could hydrolyse trehalose into glucose and take it up into the
      cell, although some glucose was liberated into the medium when incubated for
      extended periods. These results suggest that midgut trehalase plays a
      physiological role in utilization of haemolymph trehalose not in nutrient
      absorption.

PMID- 18620142
TI  - The egg-shell of Drosophila melanogaster III. Covalent crosslinking of the
      chorion proteins involves endogenous hydrogen peroxide.
AB  - Utilizing two cytochemical methods, namely, diaminobenzidine for the assay of
      peroxidases and cerium(III) chloride for the localization of hydrogen peroxide it
      was found that the enzyme exists in two out of the five egg-shell layers: the
      innermost choronic layer and the endochorion. In addition, hydrogen peroxide
      which acts as a substrate for the enzyme in vitro enabling the formation of
      covalent bonding between the egg-shell proteins, was found to be produced at the
      follicle cell plasma membrane during the last stage of oogenesis. It is concluded
      that hydrogen peroxide is an endogenous, programmed product of the follicle
      cells, responsible for the action of peroxidase in order to oxidize the tyrosyl
      residues producing di-tyrosine and tri-tyrosine bonds between the chorion
      polypeptides.

PMID- 18620143
TI  - Membrane specializations in the paired spermatozoa of dytiscid water beetles.
AB  - The paired spermatozoa of the dytiscid beetles Dytiscus marginalis and Hydaticus
      seminiger were studied by electron microscopy with the aim of examining whether
      the regions of the cell membrane in the zones of sperm conjugation might differ
      from other regions and to explore whether these cells had any other specialized
      domains of the cell membrane that could be recognized by the freeze-fracturing
      technique. The spermatozoa are conjugated along one side of the sperm head and
      proximal tail portion, called the ventral side. The cell membrane was seen to
      contain tightly packed intramembranous particles (IMPs) that were predominantly
      located in the external membrane face (the E-face). In thin sections the cell
      membrane had a ladder-like appearance at these regions and a specialized type of
      glycocalyx seen as a fluffy material containing granules. Other specialized
      membrane domains could also be recorded: a ribbon of particles in the
      protoplasmic face (P-face) of the dorsal side of the spermatozoon at the proximal
      tail portion and regularly arranged particle rows in the P-face of the distal
      tail portion. These domains corresponded to regions where the glycocalyx is
      prominent. Both the E-face and the P-face of the cell membrane were seen to
      contain numerous intramembranous particles, which suggests an active function for
      both membrane leaflets; this is in contrast to the situation in most cells where
      the particles are mainly in the P-face. The functions of the intramembranous
      particles in the specialized domains of the cell membrane remains unknown. Some
      particles may represent receptors or ion gates, others proteins with a mechanical
      function.

PMID- 18620144
TI  - The pairing of nucleolar patterns in an epithelium as evidence for a conserved
      nuclear skeleton.
AB  - The nucleoli in epidermal cells of fifth instar Calpodes and Manduca larvae
      undergo three cycles of unravelling into necklaces with condensation back to a
      dense particle or particles. Mitosis occurs before the first cycle and at the
      beginning of the third cycle. In spite of the formation and condensation of these
      nucleolar necklaces the nucleoli in the intercycle condition all have paired
      patterns. Adjacent pairs of nuclei have nucleoli that resemble one another in the
      number of their component particles, the shape and size of the particles and
      sometimes in their arrangement as mirror images. The paired patterns begin at
      mitosis and reform after necklace elongation and condensation. The patterns are
      presumed to reflect a nuclear skeleton that is paired from mitosis and conserved
      until the next mitosis. The nuclear pairing is related to the retention of mid
      bodies by sibling cells so that the epidermis is a collection of minimal two-cell
      syncytia.

PMID- 18620145
TI  - Nucleolar necklace formation in response to hemolymph ecdysteroid peaks.
AB  - Previous work on the last (fifth) larval stadium of Calpodes showed two phases of
      elaboration of epidermal nucleoli correlated with RNA synthesis, the first after
      ecdysis at the beginning of the intermolt and the second near the end of the
      stadium prior to molting. Both phases followed periods of elevated hemolymph
      ecdysteroid. The demonstration of four hemolymph ecdysteroid peaks and an
      improvement in the bismuth-staining procedure for nucleoli has prompted further
      study of nucleolar changes in relation to hemolymph edcysteroids. We have found
      that three of the four ecdysteroid peaks (I, II and IV) are followed by nucleolar
      changes. The exception is the commitment peak (III) for which there is no
      corresponding nucleolar change. The three nucleolar cycles are similar in their
      essential features. An intercycle nucleolus consists of one or a few irregularly
      shaped particles that become more densely stained and condense into a knot at the
      beginning of each cycle. The knot unfolds into a necklace which becomes beaded as
      it elongates to a length of about 23 microm. Cells have one or two, rarely more,
      necklaces presumably depending on their ploidy. At the end of the cycle the
      necklaces contract, becoming coarser and fragmented before they condense to the
      intercycle condition of central irregular cores. Whereas nucleolar necklaces are
      a general response to hemolymph ecdysteroids, mitoses are locally determined and
      are imposed over other nuclear activities at any time in the third nucleolar
      cycle.

PMID- 18620146
TI  - Cuticulogenesis correlated with ultrastructural changes in oenocytes and
      epidermal cells in the late cockroach embryo.
AB  - During late embryogenesis in a cockroach, the epidermal cells secrete two
      cuticles: the embryonic cuticle and the pharate first larval cuticle. Late
      embryogenesis begins with the deposition of the cuticulin layer of the embryonic
      cuticle. The embryonic cuticle is an atypical one. It remains relatively thin and
      a well lamellated endocuticle is usually lacking. After general apolysis of the
      embryonic cuticle the epidermis secretes the epicuticle of the first larval
      cuticle and, subsequently, a typical lamellate procuticle. During the penultimate
      phase of late embryogenesis (i.e. before general apolysis) the epidermis becomes
      larvally committed. Some epidermal cells start to differentiate into specialized
      structures of the dermal glands, whereas the differentiated oenocytes appear to
      have acquired some stability. Nevertheless, shortly before general apolysis some
      oenocytes display signs of an increased alteration of the SER. When general
      apolysis occurs, the oenocytes contain a well-developed SER. The whole of the
      oenocyte population is programmed to regress after epicuticle deposition of the
      first larval cuticle. The correlation of oenocyte regression with available data
      on cuticulogenesis, ecdysteroid titres and cuticular lipid synthesis is
      discussed.

PMID- 18620147
TI  - Fine structure and development of the silver and golden cuticle in butterfly
      pupae.
AB  - Pupae of the butterflies Danaus chrysippus and Helioconius charitonius display
      characteristic patterns of golden spots, while the pupae of the genera Euploea
      and Amauris exhibit metallic lustre over most of their surface; E. core and
      midamus more golden, A. ochlea and niavius more silvery. The absolute reflectance
      exceeds 80% at wavelengths longer than 550 nm, but drops more or less steeply at
      shorter wavelengths (shown by microspectrophotometry for E. core and A. ochlea;
      in all species this effect is caused by constructive interference of the incident
      light at Multiple Endocuticular Thin Alternating Layers (METAL cuticle). Dense,
      cuticular D layers alternate with clear, watery C layers and form over 200 double
      layers. The thickness of the D layers is fairly constant throughout the stack,
      whereas the C layers systematically increase and decrease in thickness, thus
      causing the broad bandwidth of the reflector. Connecting filaments, traversing
      the C layers in zig zag course, probably secure the mechanical stability of the
      arrangement. After drying, the C layers have vanished and the lustre is lost; the
      cuticle is now perfectly transparent, except for D. chrysippus, where it is
      partly transparent and partly yellow. The metallic reflectance develops between
      20 and 30 hr after pupal ecdysis, starting with blue colours which change via
      green to gold or silver. About half a day before emergence of the imago, the
      reflection fades again via the opposite colour sequence. Coincident with these
      colour changes, the METAL cuticle is being deposited and decomposed,
      respectively. The deposition zone immediately above the apical epidermal
      microvilli consists of about three helicoidal lamellae as in normal, non
      reflecting cuticle. The METAL cuticle is formed abruptly at the outer border of
      the deposition zone, possibly during condensation of the cuticular microfibres.
      The periodicity it is suggested is controlled either directly by the epidermal
      cells or indirectly via appropriate self-assembling processes.

PMID- 18620148
TI  - A simple mechanical method to isolate the basal lamina of insect midgut
      epithelial cells.
AB  - In mealworms (Tenebrio molitor) the midgut epithelium is surrounded by a
      1.6microm thick basal lamina of low electron density with a framework of high
      electron density imbedded in a part of it. The lamina can be isolated by
      ultrasonication followed by repeated filtrations and high-speed centrifugations,
      making large-scale preparation of the lamina for further analyses possible. The
      isolation of the basal lamina is confirmed by electron microscopy.

PMID- 18620149
TI  - The fibrous system in the extracellular matrix of hydromedusae.
AB  - The ultrastructure and the histochemistry of the fibrous system in the mesogloeal
      extracellular matrix (ECM) of two hydromedusae (Polyorchis penicillatus and
      Aglanlha digitale) has been examined. There is a fundamental difference in the
      architecture of the fibrous system between the two species. In Polyorchis, 60-150
      A thick, striated fibrils with periodicities of 60-65 A form a three-dimensional
      network which fills in the entire ECM of outer and inner mesogloea. In the outer
      mesogloea vertical fibres (up to 1.8 mum in diameter) penetrate the
      threedimensional network and branch near the exumbrellar and subumbrellar side.
      These branches impinge on a dense matrix covering the exumbrellar and
      subumbrellar surface. In Aglantha the branches of thick vertical fibres anchor at
      the subumbrellar side in a dense plexus (0.2-0.3 mum in thickness) which consists
      of two types of fibrils (35-40 and 80-100 nm in diameter). Towards the
      exumbrellar side the vertical fibres branch and intermingle with a meshwork of
      non-striated fibrils with uniform diameter (35-40 nm). These fibrils form a
      laminated structure (about 1 mum in thickness) so that fibrils of each layer
      course in the same direction but fibrils of adjacent layers run perpendicularly
      to each other. The banded pattern with periodicities of 600-640 A observed in the
      electron microscope and by histochemical methods confirm the thick vertical
      fibres and their branches to be a collagen. There is also strong evidence that
      the laminated structure in Aglantha represents layers of collagen fibrils.

PMID- 18620150
TI  - Glial cell contacts in insects: Effects of feeding on intercellular junctions.
AB  - The intercellular junctions associated with the modified glial cells of the
      perineurium have been examined in the ganglia and main abdominal nerves of the
      blood-sucking bug Rhodnius prolixus, both before and and after feeding, by means
      of freeze-fracture and tracer studies. It was found that the pleated septate
      junctions found in the main abdominal nerve have many fewer septa than those
      found in the ganglion. These junctions appear to provide the flexibility needed
      for the movement of cells which occurs to accommodate the tremendous increase in
      body size that takes place after a bloodmeal. On feeding and during the
      subsequent period of digestion the nerves stretch to double their length, yet the
      blood-brain barrier is maintained throughout. In the same manner as loosely
      interconnected tight junctions, septate junctions with fewer septa seem to form a
      junction which is able to respond readily to the stress of stretching. With
      feeding and afterwards the septate junctions become disorganized and disassemble,
      while the gap junctions and tight junctions remain intact. It is envisaged,
      therefore, that the primary function of the septate junction is adhesive.

PMID- 18620151
TI  - Elaborations of the basal surface of the cells of the Malpighian tubules of an
      insect.
AB  - Electrical measurements of membrane potential and resistance using intracellular
      microelectrodes showed that the fluid-secreting parts of the Malpighian tubules
      of Rhodnius have superficial regions different in electrical properties from the
      main body of the cell. The membrane potential in these superficial regions was
      smaller by 30-40 mV, but showed a standard depolarization on changing the
      potassium concentration of the bathing medium. The response to changes in the
      external chloride concentration also differed in the two regions, a finding that
      was reinforced by different responses to the drug, furosemide. Electron
      microscopy of the basal regions of the cells revealed many long cellular
      projections that run parallel to the cell surface and interdigitate with similar
      projections from neighbouring cells. The degree of interdigitation was examined
      by marking individual cells with alcian blue or by horseradish peroxidase
      injection. A survey of the published micrographs of insect Malpighian tubules
      shows that most have similar projections on their basal surfaces and not the
      simple basal infoldings previously supposed.

PMID- 18620152
TI  - The fine structural morphology of the midgut of adult Drosophila: A morphometric
      analysis.
AB  - The midgut of one day old Drosophilia was examined morphometrically at the
      electron microscopic level. Results suggest that parenchymal cells, with the
      exception of basal cells, possess identical functions. Drosophilia midgut cells
      are smaller than those of other insects studied, and the surface densities of the
      rER was less, indicating that its protein synthetic activity is also less than
      that of other insects.

PMID- 18620153
TI  - The structure of epidermal feet during their development.
AB  - Epidermal cells in Calpodes and other insects form basal processes or feet that
      at first extend axially and later shorten at the same time as the larval segment
      shortens to the pupal shape. The feet grow into spaces at the surfaces of other
      cells to make a basal interlacing meshwork of cellular extensions that are
      combined mechanically by their desmosomal attachments to cell bodies above and to
      the basal lamina below. Microtubules and microfilaments are linked to these
      junctions by a reticular fibrous matrix. Gap junctions on the feet may couple
      cells that are several cell bodies removed from one another. The meshwork is also
      a sieve separating the hemolymph from the spaces between cells to form an
      intercellular compartment. Entry to the intercellular compartment is through the
      sieve made by the negatively charged basolateral cell surfaces that can prevent
      the entry of positively charged molecules such as cationic ferritin. As the cells
      become columnar, coincident with the metamorphic change in segment shape, the
      feet shorten and pack more densely together. At this time the basal lamina
      buckles axially as if responding to contraction of the feet. Segment shape change
      involves cell rearrangement and relative cell movement, necessitating the
      transient loss of plasma membrane plaque attachments to the cuticle apically and
      the loss of junctions laterally. Gap junctions involute in characteristic
      vacuoles. The metamorphic reduction in cell surface area coincides with the loss
      of basolateral membrane in smooth tubes and vesicles and the turnover of the
      apical surface in multivesicular bodies. New apical plasma membrane plaques and
      new lateral and basal junctions stabilize the cells in their pupal positions.

PMID- 18620154
TI  - A mutant of bacteriophage phiX174 which infects E. coli K12 strains. I. Isolation
      and partial characterization of phiXtB.
AB  - A mutant of bacteriophage phiX174 has been isolated which infects K12 strains of
      E. coli. This mutant, phiXtB, also infects strains C and B, though at reduced
      efficiencies. phiXtB's properties are summarized as follows: (1) phiXtB has an
      altered plating temperature range; (2) phiXtB particles sediment slightly faster
      and are slightly more dense than phiX174 particles; (3) phiXtB's replication
      involves intracellular DNA forms like those found in phiX-infected cells and a
      possible new species not previously seen in phiX-infected cells.

PMID- 18620155
TI  - The cellular localization of long chain fatty acids in sponges.
AB  - Examination of fractionated sponge tissue shows that long chain fatty acids
      (LCFAs) occur in high proportions in cell membranes. This conclusion refutes a
      recent suggestion made by other workers that sponge membranes would contain
      conventional fatty acids similar to those found in membranes from other
      organisms.

PMID- 18620156
TI  - Immunocytochemical staining of central neurones in Periplaneta americana using
      monoclonal antibodies to choline acetyltransferase.
AB  - Immunocytochemical mapping of cholinergic neurones in the CNS of the cockroach
      Periplaneta americana has been attempted using monoclonal antibodies to choline
      acetyltransferase (ChAT, acetyl-CoA: choline O-acetyltransferase, EC 2.3.1.6).
      Monoclonal antibodies 11 255 and 1E6 raised against rat brain ChAT and 1C8 raised
      against Drosophila melanogaster ChAT were ineffective in staining Periplaneta
      neurones. However, the cytoplasm of certain neuronal cell bodies was stained by
      monoclonal antibody 4D7 prepared against rat ChAT. Staining of cell bodies by 4D7
      was enhanced following in vivo pre-treatment with colchicine. The staining of
      specific neurones by monoclonal antibody 4D7 indicates that these cockroach cells
      are rich in a protein with antigenic determinants resembling those of vertebrate
      ChAT. For some unidentified neurones, 4D7 staining is associated with the
      presence of acetylcholinesterase indicating that this monoclonal antibody offers
      a probe for mapping cholinergic neurones in the CNS of Periplaneta americana. The
      fast coxal depressor motoneurone (D(f)) was not stained by monoclonal antibody
      4D7. Some neuronal processes in the sixth abdominal ganglion, and sensory cell
      bodies in the cerci were lightly stained by monoclonal antibody 4D7 following pre
      injection of animals for 36 hr with colchicine.

PMID- 18620158
TI  - Temperature and the transpiration of water through the insect cuticle.
AB  - The effervescence that occurs when an insect is immersed in a mixture of liquid
      paraffin and butanol indicates that the waterproofing barrier may be very close
      to the surface, that this barrier varies greatly in permeability in different
      areas, and that it is readily permeable in the newly moulted insect, but becomes
      far more resistant as the cuticle hardens. At the height of the effervescence the
      streams of expanding vesicles, that come from the surface, arise from fixed
      points-which suggests that the water is escaping from the terminations of the
      tubular filaments. It is shown that if the intact insect is warmed in a solution
      of ammoniacal silver at a succession of rising temperatures the argentaffin
      component of the extracuticular waterproofing layer is usually the first location
      of silver reduction, to be followed by the contents of the epicuticular channels
      piercing the outer epicuticle, the substance of the inner epicuticle, and the
      distal portions of the pore canals. The temperature at which this silver staining
      increases most rapidly parallels (approximately) the temperature at which
      transpiration in dry air begins to rise most steeply. It is inferred that both
      responses are probably dependent on the same temperature effects in the
      waterproofing lipids.

PMID- 18620157
TI  - Quantitative ultrastructural changes of the endodermal cells in the early chick
      embryo analysed by stereological methods.
AB  - The ultrastructure of endoderm cells of the area pellucida has been analysed in
      the chick embryo by stereological methods. These cells show a specific
      subcellular evolution which can be correlated with several aspects of
      morphogenetic behaviour. The cell form coefficient (CFc) changes notably from
      stage 5 (0.683) to stage 8 (0.446) accompanying the transformation of this layer
      into a squamous epithelium. An increase of the nuclear surface density is
      observed and is discussed in relation to the control of nucleocytoplasmic
      interchange. The mitochondrial volume and surface densities remain constant
      (3.12% of cellular volume and 0.727 mitochondria/mu(3) respectively). The
      endodermal cells possess higher levels of vitelline reserves (lipid bodies, 6.97%
      and yolk droplets, 8.90%) than other cellular types of the chick embryo. This
      fact is discussed with respect to the role of the endoderm in the phagocytosis of
      yolk. The RER length density shows an increase that could be related to some
      specific changes of the extracellular matrix during this period, but this fact
      remains to be demonstrated in relation to changes of Golgi membranes.

PMID- 18620159
TI  - Similarity in yolk-platelet structure of an ancient bony fish (Acipenser) and an
      ancient reptile (Sphenodon).
AB  - Lipovitellin-phosvitin crystals from oocytes of the sturgeon (Acipenser boeri L.)
      and the tuatara (Sphenodon punctatus [Gray]) have been shown to he orthorhombic
      like all such known crystals from vertebrates higher than cyclostomes. Lattice
      parameters and projected crystal views also resembled closely the hitherto known
      cases. The high evolutionary conservation of this crystal structure probably
      reflects a cell-biological significance of the tertiary structure of crystal
      constituents, especially of the lipovitellines. A comparative consideration of
      crystallographic data from cyclostomes and higher vertebrates suggests that
      cyclostomes started with one species and all higher vertebrates with two species
      of lipovitellin molecules.

PMID- 18620160
TI  - Fine structure and development of the large sensilla basiconica on the antennae
      of sphecid wasps.
AB  - The large sensilla basiconica of different species of the Sphecoidea are
      similarly shaped. Each sensillum is associated with a large number of sense cells
      as well as three envelope cells, the second of which is doubled. During early
      development degenerating supernumerous envelope cells were observed. After the
      early cell degeneration four envelope cells remain. The inner envelope cell
      secretes a temporary dendritic sheath, the three outer envelope cells secrete the
      various parts of the cuticular cone. After the secretion of the cone, envelope
      cell 3 degenerates.

PMID- 18620161
TI  - Transcription of double-stranded RNA in cytoplasmic polyhedrosis virus in vitro.
AB  - RNA polymerase associated with cytoplasmic polyhedrosis virus, which contains
      double-stranded RNA as a genome, synthesizes single-stranded RNA in vitro. The
      RNA product has the same size distribution to the genome segments, showing two
      fractions on a glycerol concentration gradient centrifugation. Each fraction of
      the synthesized RNA hybridized specifically with the corresponding size fraction
      of the denatured genome RNA segments. Only after the transcription has been
      carried out over the whole length of each genome segment, the single-stranded RNA
      product leaves the virus particle. It seems that the transcription of every
      segment starts at the same time, although the transcribed RNA for the shorter
      segment group is released from a virion faster than the larger group.

PMID- 18620162
TI  - Effects of glycerol and freezing on the appearance and arrangement of
      microtubules in three different systems: A freeze-substitution study.
AB  - Effects of glycerol and freezing on microtubules in three different systems viz.
      the ovaries of Notonecta glauca, the sperm tails of Notonecta glauca and the
      hyphae of the fungus Phanaerochaete velutina have been studied by means of freeze
      substitution. The protofilamentous substructure of microtubules is visible in
      positive image whether or not the tissues are treated with glycerol prior to
      freezing, suggesting that it is the freezing which allows this by the weakening
      of hydrophobic bonding between protofilaments. Glycerol, used as a
      cryoprotectant, causes a re-arrangement of the microtubules which is proportional
      to the concentration of, and the duration of exposure to, glycerol. This
      rearrangement of microtubules is greater in systems where the microtubules are
      not inter-linked than those where microtubules have obvious intertubule linkages.
      Rates of cooling on freezing affected the degree of rearrangement and was less
      with propane than with Freon 22. Possible explanations for these effects have
      been discussed.

PMID- 18620163
TI  - Endodermal secretion of chitin in the 'cuticle' of the earthworm gizzard.
AB  - The gizzard of earthworms is definitely of endodermal origin. Contrary to the
      opinion that tissue of endodermal origin is unable to synthesize chitin, the
      gizzard epithelium secretes large amounts of chitin-containing material which has
      special properties. 28.7 +/- 5.7% of the dry weight proved to be chitin; the
      microfibres form a random felt-like texture. They are not arranged in layers
      comparable to those found in arthropod cuticle. The protein content amounts to
      44.9 +/- 7.1% of the dry weight; the remaining material contains at least uronic
      acids. In the protein matrix large amounts of the enzymes amylase and protease
      have been demonstrated. As the so-called cuticle is sloughed off at the lumen
      side, these enzymes are mingled with the gut contents. It might be called a
      gastric shield, as it closely resembles this structure, widespread among
      Mollusca. The thickness of the gizzard cuticle varies between 10 and 90 mum in
      Lumbricus terrestris and 10-50 mum in L. rubellus. Autoradiography has shown that
      it is replaced at a high rate. In Lumbricus terrestris it is renewed completely
      in less than 60 hr, and in smaller Lumbricus rubellus, this takes place in about
      48 hr. These results are in agreement with the biochemical findings.

PMID- 18620164
TI  - An electron microscopic study of a 'Sertoli-like' cell in the testis of a
      barnacle, Balanus.
AB  - The organization of a 'Sertoli-like' cell (SLC) is described in the testis of a
      barnacle, Balanus eburneus. Underlying a relatively thick basal lamina are 'sheet
      like' cytoplasmic extensions that develop from the base of the SLC and almost
      completely enclose the germ cells. Junctional structures are frequently observed
      between the SLCs and between an SLC and a developing germ cell. Portions of the
      SLC extend deep into the testis and subdivide into branches. Developing sperm are
      seen within inpocketings of the plasmalemma of the branches. Noteworthy among the
      SLC's organelles are large, well-developed mitochondria, an abundant smooth
      endoplasmic reticulum and masses of glycogen particles. Intercellular bridges are
      present between germ cells which are at the same stage of development. In some
      respects the organization of the SLC in B. eburneus is suggestive of that in the
      Sertoli cell in the testis of vertebrates.

PMID- 18620165
TI  - Accumulation of cadmium by the fourth instar larva of the fly Chironomus thummi.
AB  - Accumulation and effects of cadmium were investigated in Chironomus thummi larvae
      exposed to 10, 100 and 250 mug radiolabeled Cd/1 for up to 4 days. (1) After 4
      days, average cadmium accumulation was 6.6 ng Cd/mg dry weight (10 mug Cd/1
      exposure) and 177 ng Cd/mg dry weight (250 mug Cd/1 exposure). (2) Dissection
      studies showed that by 32 hr of exposure to both cadmium concentrations, 63.5
      81.4% of accumulated cadmium was confined to the posterior midgut epithelium.
      Light microscope autoradiography similarly showed accumulations of cadmium in
      posterior midgut epithelium and smaller amounts in fat body and muscle. Little
      cadmium was associated with Malphigian tubules, haemocoel, anterior midgut or
      exoskeleton. (3) After exposure to 10 or 250 mug Cd/1, 60-75% of cadmium in
      ultracentrifuged homogenates of whole animals or dissected guts was associated
      with the resulting supernatant. When supernatants were further analyzed by gel
      chromatography, cadmium eluted with both a high and low molecular weight peak.
      The relative proportions of cadmium in the two peaks varied with concentration
      and length of exposure. (4) Transmission electron microscopy of posterior midgut
      cells from animals exposed to cadmium demonstrated frequent mitochondrial
      lesions. Exposure to high cadmium concentrations caused some posterior midgut
      cells to undergo generalized structural degeneration.

PMID- 18620166
TI  - Structure of the larval midgut of the fly Chironomus thummi and its relationship
      to sites of cadmium sequestration.
AB  - The midgut structure of 4-7 day old fourth instar Chironomus thummi larvae was
      investigated with the light arid electron microscopes. Four regions are present
      which may be identified by the following major features: (1) Anterior I: this is
      the region under the esophageal invagination. (2) Anterior II: short microviili
      characterize these cells. Long narrow, basal plasma membrane infoldings
      associated with mitochondria are conspicuous. This region is hypothesized to be
      important in ion and fluid transport. (3) Anterior III: numerous crystals are
      seen in these cells. Storage is proposed to be a major function of this region.
      (4) Posterior: these cells have long microviili, extensive RER, many Golgi, and
      short basal plasma membrane infoldings. Posterior cells probably function in
      secretion of digestive enzymes and absorption of nutrients. Cadmium is
      sequestered by the midgut, almost exclusively in the posterior cells. This
      phenomenon is discussed.

PMID- 18620167
TI  - Transport of peroxidase through the midgut epithelium of Glossina M. Morsitans
      (diptera, glossinidae).
AB  - The peritrophic membrane (pm) of teneral female tsetse flies, Glossina morsitans
      morsitans, did not extend to the full length of the midgut 1-12 hr after
      emergence. The ingested blood did not reach the posterior part of the midgut (p
      part), and the crop still contained food 12 hr after feeding. In these flies, the
      p-part contained the remains of the larval gut, the meconium, and bacteria.
      Ferritin molecules fed to tsetse females together with human serum were only
      found in the endoperitrophic space of the gut. This electron-dense tracer did not
      penetrate and cross the pm. On the other hand, ingested peroxidase passed the pm,
      and was transported through intercellular clefts, the basal labyrinth and the
      basal lamina to the hemolymph. This uptake was observed in the anterior part and
      to a smaller extent in the middle part of the midgut within 2 hr after feeding.
      Peroxidase was incorporated from the hemolymph into fat body cells, where it was
      found 2 hr and later after feeding. Pinocytosis of the tracer molecules, as an
      additional intracellular pathway to the intercellular route of transport, could
      not be demonstrated.

PMID- 18620168
TI  - Ultrastructure of the rectal sac, the site of water vapour uptake from the
      atmosphere in larvae of the oriental rat flea Xenopsylla cheopis.
AB  - A portion of the hindgut of Xenopsylla cheopis larvae, the rectal sac, is
      extraordinarily enlarged and differentiated into a specialized organ displaying
      well-elaborated transporting epithelia. This organ is unique among insect recta
      because of gutter-like arrangement of two ultrastructurally distinct cell types
      with an asymmetrical position of the membranemitochondria complexes. The cells of
      the dorsal gutter have highly folded apical plasma membranes on the lumen side.
      The cells of the ventral gutter show deep infoldings of the basal plasma membrane
      on the haemolymph side. Less elaborate folds originate from the opposite sides of
      the cells. The nuclei of the dorsal epithelial cells are located in the basal
      part; those of the ventral cells in the apical portion of the cell. The
      ultrastructural features of the rectal sac, its ventilation synchronized with
      rhythmic opening of the anus during phases of active water vapour uptake, as well
      as the reversible arrest of uptake by experimental occlusion of the anus, reveal
      that condensation and uptake of atmospheric water take place in this organ.

PMID- 18620169
TI  - A permeability barrier in the testis of an insect Triatoma: A freeze-fracture and
      lanthanum tracer study.
AB  - In vertebrates, the testicular permeability barrier has been the subject of
      numerous studies. Some recent observations also indicate the existence of such a
      barrier in some invertebrates, e.g. insects and worms. With the aim of
      determining whether the morphological features of the blood-testis barrier
      generally found in vertebrates can be extended to other animals, we studied the
      testis of the insect Triatoma infestans using electron-dense tracers and freeze
      fracture techniques. This organ is divided into cysts timed in synchroneous
      maturation. The intercellular tracer (lanthanum hydroxide) freely penetrates the
      basal areas of the seminiferous epithelium surrounding spermatogonia and
      spermatocytes devoid of synaptonemal complexes (pre-leptotene and leptone).
      Zygotene spermatocytes indicate the establishment of the barrier. Freeze-fracture
      techniques exhibit the morphological correlate of the barrier consisting of 9-10
      nm particle rows on the P faces of the Sertoli cell membranes. These rows are
      relatively loose showing an undulating disposition and correspond to the septate
      junctions found in thin sections. The percolation of intercellular tracers
      demonstrates that septate junctions between the basal membraneous areas of
      Sertoli cells possess the barrier properties.

PMID- 18620170
TI  - Fusion of myocytes with larval muscle remnants during flight muscle development
      in the Colorado beetle.
AB  - The transformation of the slow contracting larval m. obliquus lateralis caudalis
      II during metamorphosis into the asynchronous indirect flight muscle, m. obliquus
      lateralis dorsalis, in the Colorado beetle, Leptinotarsa decemlineata, was
      examined by electron microscopy. Particular attention was paid to the fate of the
      larval muscle fibres, the origin and behaviour of the myoblasts for flight muscle
      development and the change of the myofibrillar filament lattice of the larva into
      that of the adult. In the pre-pupal period, the larval muscles dedifferentiate
      and fragment. At pupation, the muscle fibres consist of cell fragments containing
      very few myofibrils. The sarcoplasmic reticulum and the transverse tubular system
      are greatly reduced. The number of myoblasts developed from satellite cells by
      mitosis increases considerably. They penetrate the muscle fibre and surround the
      cell fragments. The new fibres of the flight muscle develop from myocytes fused
      with the larval fragments. The larval basal lamina, surrounding the cell
      fragments and myoblasts, is present in pupae up to 1 day old. In pupae about 2.5
      days old new myofibrils appear that have the adult filament lattice. The insect
      muscle transformation and the repair of vertebrate muscle after injury show
      striking resemblances.

PMID- 18620171
TI  - The ontogenetic development of refracting superposition eyes in crustaceans:
      Transformation of optical design.
AB  - We have investigated, comparatively, the ontogenetic development of the compound
      eye in larvae of a mysid (Neomysis) and a euphausiid (Thysanoessa) species and
      found it to be close to identical in the two species. The larval eye is of
      apposition type with special adaptations for planktonic life. The elongated
      dioptric apparatus is devoid of screening pigment and instead has a proximal lens
      optically isolating the ommatidium. The pigmented retina is extremely compressed
      making the eye largely transparent and presumably suitable for a planktonic life.
      The presence of this specialized type of eye in the planktonic larvae of
      euphausiids was known before but it is intriguing to find exactly the same type
      in mysids, spending their entire larval life as embryos in the female marsupium.
      A possible explanation is offered if mysids earlier in evolution had planktonic
      larvae. Upon reduction of free-living larvae, the transparent type of eye may
      have been preserved because there is no selection pressure on the larva to change
      it. In late larval life, both species transform their eyes to a refracting
      superposition type typical for adult mysids and euphausiids. The process of
      transformation and the functional connection between transparent apposition and
      superposition is described.

PMID- 18620172
TI  - The virgin bursa copulatrix of the butterfly, Calpodes.
AB  - The different parts of the bursa copulatrix of virgin females of Calpodes ethlius
      have fine structures consistent with their different functions. The thin pitted
      cuticle of the bursal sac and its underlying epithelium suggest an absorptive
      function, with their 'pores' and numerous mitochondria respectively. The highly
      folded junctional region with its robust muscle and epithelium anchored to the
      thick folded spinous cuticle by sockets and their tonofibrillae suggest a holding
      structure capable of great muscular activity. The bursal duct with its hardened
      cuticle might serve to hold the body of the elongated, cone-shaped sperm sac
      straight and in position so that its contents might be more easily squeezed out
      into the seminal duct, whose opening is adjacent to the open end of the sperm
      sac.

PMID- 18620173
TI  - The ovaries and changes in their structural components at the end of
      vitellogenesis and during vitelline membrane formation in the butterfly,
      Calpodes.
AB  - The eight ovarioles of Calpodes ethlius are meroistic and polytrophic with seven
      nurse cells per follicle. The follicles consisting of oocyte, nurse cells and
      surrounding follicular cells are connected by interfollicular bridges, whose
      cells are characterized by bundles of microtubules which appear, with some fine
      filaments, to terminate on or near to the plasma membrane at hemidesmosomes. The
      ovariolar sheath consists of tightly knit circular and longitudinal muscles which
      are heavily tracheated. The ovariolar duct consists of more loosely arranged
      circular and longitudinal muscles and an inner epithelial layer, also tracheated.
      The vitelline membrane appears to be secreted largely by the oocyte first as an
      electron-lucent layer which becomes gradually more electron-dense, probably as a
      result of addition of material from the follicular cells. Overlapping plate-like
      structures on the outer surface of the fully formed vitelline membrane may
      provide waterproofing.

PMID- 18620174
TI  - Structure and formation of the chorion in the butterfly, Calpodes.
AB  - The hemispherical eggshell of Calpodes consists of a domed dorsal surface of thin
      inner endochorion and a thick, lamellate, outer exochorion, and a flat bottom of
      predominantly unlamellated endochorion. The endochorion is traversed by small
      pores and the exochorion by larger ones, which are formed by the withdrawal of
      processes from the follicular cells. The presence of a phenoloxidase in the
      ovariolar ducts, lateral and common oviducts and in ovulated eggs, and the
      stability of ovulated eggs suggest that stabilization of the eggshell is
      accomplished through quinone tanning. However, the endochorion, which is soluble
      in sodium dodecyl sulphate (SDS), is more likely cross-linked by di- and tri
      tyrosyls through the action of a peroxidase, present in the cells of the
      ovariolar duct and in the endochorion.

PMID- 18620175
TI  - Theory of microtomy artefacts in arthropod cuticle.
AB  - Arthropod cuticles observed in section generally present alternating clear and
      dark bands. These have often been interpreted in terms of superimposed layers of
      different structure or composition. It has been shown, however that this material
      is homogeneous, and is formed by a twisted arrangement of microfibrils. The dense
      bands correspond actually to a microtomy artefact and they form dark single
      spirals in certain distorted areas of the cuticle. A model was proposed,
      involving the interaction between knife motion and microfibrils; it will be
      referred to as the stepped model, since the proposed mechanism results in the
      formation of steps at the surface of sections, on both faces. These steps are
      limited by structures resembling crests or cliffs, whose regular distribution
      produces alternating thick and thin bands in the section. This explains the
      observed contrast (Bouligand, (1972)). Two very interesting models were proposed
      later (Gordon and Winfree, (1978)) and are referred to as the cos F model and the
      sand model, but steps and crests are absent in these models. However, Giraud
      Guille ((1986)), has shown very clearly the existence of these crests, which seem
      to be quite essential in this microtomy artefact. To clarify the debate, the
      texts defining the initial and the two new models are reproduced here and the
      difficulties encountered by each model are discussed. A mathematical formulation
      of this artefact is presented in an appendix to the present article; this leads
      to a more complete discussion of the possible models. Other factors are also
      taken into consideration: microfibril orientation and staining. The main factor
      of contrasts is undoubtedly the variation in thickness over a single section, as
      proposed in the stepped model.

PMID- 18620176
TI  - Cell shape, spatial patterns of cilia, and mucus-net construction in the ascidian
      endostyle.
AB  - The endostyle of the ascidian Ciona intestinalis secretes a mucus-net composed of
      regularly spaced longitudinal and transverse mucoprotein filaments. It is a
      gutter-shaped organ composed of eight different longitudinally aligned epithelial
      zones numbered 1-8. Each zone, with the exception of zone 7 which is unciliatcd.
      has a characteristic cell shape and spatial pattern of cilia and microvilli.
      Zones 1.5 and 8 are composed of multiciliated cells, and zones 2,3,4 and 6 of
      monociliated cells. Cell apices in zones 2, 3 and 4 are rectangular in cross
      section, and bear highly ordered rows of cilia. Spacings between cilia both
      within and between rows are different in each of these zones, but they are
      similar to interfilament spacings in the mucus-net. The basic structure of the
      mucus-net is probably secreted and constructed by secretory cells and cilia in
      zones 1-4. Further secretion may be added in zones 6 and 7 whilst cilia in zones
      5, 6 and 8 propel the net out on to the inner surface of the pharynx where it
      acts as a food filter. The highly organized and structurally complex pattern of
      ciliated epithelia in the ascidian endostyle is surprising when compared with the
      endostyle of the cephalochordate Branchiostoma lanceolatum, which is composed
      entirely of monociliated cells that differ very little in structure between
      epithelial zones.

PMID- 18620177
TI  - Ultrastructural and histochemical observations on electroejaculated
      spermatophores of the palaemonid shrimp, Macrobrachium rosenbergii.
AB  - Spermatophores obtained by electroejaculation from mature males of Macrobrachium
      rosenbergii were studied by light microscopy and by transmission and scanning
      electron microscopy. Upon electrical stimulation, single spermatophores were
      usually extruded simultaneously from each gonopore and frequently became firmly
      adherent to one another forming a compound spermatophore. Individual
      spermatophores were pod-shaped. 0.5-1 cm long, 2-3 microm in diameter and
      consisted of a lateral sperm mass, a medial mucus mass, and a noncellular
      capsule. The capsule was a single-layered PAS-reactive structure composed of
      fine, intertwining fibrils and almost completely surrounded the sperm and mucus
      masses. On its outer surface were large. AB-reactive globules of flocculent
      material partially surrounded by finger-like extensions of a canaliculated
      reticulum composed of fine, intertwining fibrils. The canaliculated reticulum may
      permit fluid imbibition by the spermatophore. Forming a central band within the
      capsule were many small membrane-less AB/PAS-reactive granules. The lateral sperm
      masses consisted of unistellate spermatozoa embedded in an AB/PAS-reaetive matrix
      composed of globules of flocculent. AB-reactive material and a highly plastic
      canaliculated and thread-filled reticulum. The reticulum itself consisted of
      fine, intertwining fibrils. The threads within the interstices of the reticulum
      were long, curving structures, 30-36 nm in diameter. The function(s) of the
      canaliculated and thread-filled reticulum within the sperm mass is not known at
      this time. The medial mucus mass was similar in fine structure and histochemical
      reactivity to the sperm mass, except that spermatozoa were lacking. It is
      apparent that the spermatophore of M. rosenbergii consists of relatively few
      complexly arranged structural and macromolecular components designed to transport
      and protect the spermatozoa.

PMID- 18620178
TI  - Origin of myoblasts involved in the formation of the flight muscles of a
      butterfly (Pieris brassicae).
AB  - The larval muscle precursors of the dorsal longitudinal flight muscles of Pieris
      brassicae were examined by electron microscopy at five developmental stages of
      the fifth larval instar. At the beginning of this instar, a large neuromuscular
      area (NMA) was observed along the larval muscle precursors, on the side of the
      muscle where the nerve comes into contact with it. This area was delimited by the
      basement membrane of the muscle and by a thicker external basal lamina and
      contained nerve branches, tracheae, neuromuscular endings and cells with a
      cytoplasm rich is free ribosomes. Cells similar to the ribosome rich cells of the
      NMA were located along the motor nerves supplying the larval muscle precursors in
      a compartment joined to the NMA. From 78 hr after the fourth moult onwards, the
      ribosome-rich cells increased in number, accumulated inside the NMA and in the
      space around the nerves. Then they penetrated the muscle fibre via the channels
      of the transverse system. These cells were the myoblasts that later help to form
      the flight muscles. As regards their earlier origin, they do not seem to derive
      from cells formed from larval fibre nuclei, but might be present together with
      the muscle precursors, and along the nerves from the beginning of larval
      development. The differences with the Nematoceran Diptera are discussed.

PMID- 18620179
TI  - Modulation of cytoskeletal organization during insect follicle cell
      morphogenesis.
AB  - Follicle cell morphogenesis during Rhodnius oogenesis involves extensive changes
      in lateral follicle cell shape, creating a patent epithelium. Cytoskeletal
      elements are involved in this cell shape change as assessed by investigating the
      relative abundance, orientation and dynamics of the follicle cell microtubule and
      microfilament cytoskeleton. Anti-tubulin immunofluorescence and transmission
      electron microscopy revealed the cytoskeletal organization from pre-follicular to
      post-vitellogenic follicle stages. A well-developed cylindrical arrangement of
      longitudinally orientated microtubules is present beneath the plasmalemma of the
      non-patent pre-vitellogenic and apical vitellogenic follicle cells. In contrast
      patent lateral vitellogenic follicle cells contain a dispersed distribution of
      microtubules in both longitudinal and cross-sectional planes. Prominent
      microfilament bands are not abundant in the pre-vitellogenic or apical
      vitellogenic follicle cells. The lateral vitellogenic follicle cells do however
      contain a prominent band of microfilaments in the subplasmalemmal area and in the
      projections connecting to adjacent cells and the apical microvilli. The changes
      in cytoskeletal arrangement in lateral follicle cells during vitellogenesis
      emphasize a third essential component, in addition to juvenile hormone stimulated
      [NA(+)K(+)] ATPase cell shrinkage, and cell junctional modulation, for the
      formation of a patent follicle cell epithelium in Rhodnius.

PMID- 18620180
TI  - Nurse cell-oocyte interaction: a new F-actin mesh associated with the microtubule
      rich core of an insect ovariole.
AB  - Fluorescent staining of Rhodnius prolixus ovarioles with rhodaminylphalloidin
      revealed an elaborate interconnecting meshwork of F-actin encasing the
      microtubule rich core. The thick actin struts have branches extending partially
      into the nurse cell lobes extending from the syncytical core. Basally the network
      ends at the nurse cell-pre-follicular interface and does not extend into the
      trophic cords. Light microscopy, TEM and SEM show the dense fibrous struts have
      numerous branch points creating a porous cylindrical collar at the core
      periphery. The filaments are organized in a dense felt-like anisotropic meshwork
      rather in parallel arrays. This morphology coupled with the stability of the
      entire structure in extraction procedures suggests the actin filaments are
      crosslinked, presumably by associated proteins. Detergent extraction experiments
      indicate isolation of the mesh is possible. Comparison of Nomarski DIC images
      with polarizing microscopy images of the same preparations show the F-actin
      struts are not birefringent while the microtubules of the core are highly
      birefringent and resistant to nocodazole. Indirect immunocytochemical staining of
      sections for actin confirmed the F-actin distribution visualized with phalloidin
      and contrasted markedly with staining pattern for tubulin. The discovery of this
      prominent actin meshwork must now be incorporated into models attempting to
      explain the mechanisms underlying polarized nurse cell-oocyte transport.

PMID- 18620181
TI  - Corpus luteum formation and ovulation in the butterfly Calpodes.
AB  - The first corpus luteum of each ovariole is formed initially from the epithelial
      plug of cells which underly the first leading oocyte through autolysis,
      characterized by increased acid phosphatase activity, autophagy and lipophilic
      material. Later autolysis spreads progressively to apposing follicular cells,
      degeneration moving upwards until the leading oocyte is in the ovariolar duct,
      resulting in ovulation. All subsequent corpora lutea are compound structures,
      comprising the degenerating follicle of the newly shed eggs as well as remnants
      of previous corpora lutea. The interfollicular bridge cells appear to envelope
      the mature follicle during corpus luteum formation, thereby giving some support
      to the ovariole as a follicle disintegrates und the egg is shed.

PMID- 18620182
TI  - The development of the plasma membrane reticular system in the fat body of an
      insect.
AB  - Several insect tissues have plasma membranes that are folded inwards to make a
      subsurface reticulum on faces that are exposed to hemolymph. The infolds have
      been called plasma membrane reticular systems (RSs) to distinguish them from the
      somewhat similar structures found in transporting epithelia. They are
      characterized by having negative charges on the plasma membranes of the
      entranceways and by the concentration of some hemolymph proteins in their lymph
      spaces. Their formation and loss in the fat body has been studied by scanning
      electron microscopy during the fifth stadium of Calpodes ethlius (Lepidoptera,
      Hesperiidae). Fat body cells begin the fifth stadium arranged in ribbons with the
      cells linked together by a fringe of processes. In the first stage many more
      processes form. These partially fuse together in the second stage, leaving a
      subsurface reticulum connected by narrow entrances to the lateral cell faces and
      the face below the basal lamina. Both the cell processes and the reticular
      systems that they enclose are usually axially orientated. The completed RS
      persists for the second half of the intermoult devoted to larval syntheses when
      the concentration of hemolymph proteins rises. After protein sequestration prior
      to pupation the RS is lost and the fat body returns to being a tissue of rounded
      cells linked by a few enmeshed processes.

PMID- 18620183
TI  - Integument of the tapeworm scolex. 1. Freeze-fracture of the syncytial layer,
      microvilli and discoid bodies.
AB  - The tegument of cestodes is the most important and structurally complex metabolic
      interface between these parasites and the hostile environment in which they
      reside. In spite of the complex metabolic, regulatory and immunological
      properties of this layer of syncytial cytoplasm, which are relatively well known,
      the detailed fine structural anatomy of the cestode tegument remains equivocal.
      The present study therefore reports the freeze-fracture morphology of the
      tapeworm (Hymenolepis diminuta) tegument. The most important features revealed by
      analysis of platinum replicas of freeze-fractured tapeworm scolex-neck tegument
      include: (a) presence of highly ordered linear and/or circumferentially
      orientated rows of intramembrane particles situated on the PF fracture face of
      microvillar plasma membrane, which may participate in movements of the
      microvilli, (b) presence of apparent 'pores' (11 nm in diameter) at the tips of
      the tegumentary microvilli, which could serve as regulated gates through which
      extramicrovillar surface coating materials can be extruded, and (c) the alignment
      of cytoplasmic discoid bodies into positions at the bases of the surface
      microvilli such that they could move into the core of each microvillus and
      thereby release their contents for extrusion (via the pores) onto the outer
      surface of the microvilli. Concomitantly, the limiting membrane of the discoid
      bodies could be added to the tegument plasma membrane and thereby contribute to
      the rapid turnover of the tegumentary surface. This study provides the first
      detailed account of the ultrastructural anatomy of the tapeworm tegument and is
      intended to serve as a point of reference for future investigations of tapeworm
      tegumentary functions.

PMID- 18620184
TI  - Sealing junctions in a number of arachnid tissues.
AB  - The junctions present in the central nervous system (CNS), midgut, silk gland and
      venom gland of arachnids have been investigated. Special care was taken to try to
      locate tight junctions in tissue other than CNS but they were not found in any of
      the other tissues. The detailed structure of the junctions present are discussed.
      The tight junctions present in CNS are somewhat different in appearance and
      fracturing behaviour to most vertebrate tight junctions and closely resemble only
      those found in Urochordates (a non-vertebrate chordate). The two types of septate
      junctions found in the other tissues belong to the pleated septate and smooth
      septate classes but show some interesting differences. It appears probable that
      the septate junctions in Arachnida, Merostomata and Myriopoda have different
      fracturing properties from those found in other arthropods. The finding that only
      septate junctions are present in most arachnid tissues, although tight junctions
      are present in CNS, is discussed in the context of the sealing function of
      septate junctions in invertebrate tissues.

PMID- 18620185
TI  - Ultrastructural study of oogenesis and yolk formation in an opisthobranch
      mollusc, Runcina.
AB  - Runcina is a hermaphroditic opisthobranch mollusc of small size. It produces
      large eggs, rich in yolk substances, and it is thus ideal for studying the
      mechanisms of vitellogenesis. The rough endoplasmic reticulum and the Golgi
      apparatus appear to be involved in early build up of yolk precursors. Endocytotic
      vesicles carrying yolk proteins, taken up from the haemolymph, dominate yolk
      formation at a later stage. The findings presented in this study enhance the
      proposition of a dual pathway of auto- and heterosynthesis in yolk formation. It
      is not found that the yolk bodies in Runcina acquire lysosomal enzymes in order
      to digest the perivitelline fluid, as has been described for some pulmonates. The
      importance of the role played by the follicle cells in oocyte development is
      discussed.

PMID- 18620186
TI  - Ultrastructural and physiological studies of the contraction of the trunk
      musculature of Sagitta setosa (chaetognath).
AB  - The relationships between structure and function of the contractile apparatus of
      the trunk musculature in the chaetognath Sagitta setosa, were studied by electron
      microscopy and mechanical recordings. We also investigated the nature of the
      neuromediator at the synaptic level. Contraction, relaxation and stretch can be
      explained on the sliding model basis. The primary filaments are linked to a large
      Z line, via C filaments. These C filaments vary in length according to the
      mechanical states of the contractile apparatus. These muscles are directly
      excitable by electrical current, high K(+) solutions induced depolarization, or
      exogenous acetylcholine. The characteristics of the unitary contractile response
      (twitch) and the effects of the frequency of stimulation set up the contractions
      of Sagitta among the fastest in the animal kingdom. Acetylcholine appears to be
      the best candidate for the mediator released at the neuromuscular junction. Its
      effect on the post-junctional membrane seems to require a receptor of the
      nicotinic type.

PMID- 18620187
TI  - Physiological and cytochemical studies of Ca in the primary muscle of the trunk
      of Sagitta setosa (chaetognath).
AB  - The movements of Sagitta are conditioned by the presence of Ca(2+) in the
      external medium. When this ion is removed from artificial sea water, animals do
      not move. They swim again when Ca(2+) is present. Among the problems raised by
      this observation, we have studied the role of Ca(2+) in the contraction of the
      primary musculature. Physiological experiments show the central importance of the
      extracellular Ca(2+) and of its translocation through the membrane during the
      initiation of the contraction. Cytochemical data correlate these observations.
      They show that Ca(2+) is localized mainly at the level of the plasma membrane,
      its invaginations and in the poorly developed SR (less than 2% of cell). Like SR,
      mitochondria accumulate Ca(2+) but do not seem to participate in the regulation
      of these Ca movements except in abnormal situations. La(3+) blocks the entry of
      extracellular Ca(2+) and attaches to the membranes; this fixation is not the same
      on the plasma membrane and in its invaginations. The contractile apparatus of
      Sagitta primary musculature show remarkable specializations (Duvert and Savineau,
      1986). It is composed of ribbon-shaped myofibrils of regular thickness surrounded
      by external membranes implicated in the fixation and the translocation of a pool
      of Ca(2+) necessary for initiating contraction. The poorly developed SR and the
      mitochondria probably modulate the functioning of the two types of fibres (A and
      B).

PMID- 18620188
TI  - The ability of an epithelium to survive removal of the basal lamina by enzymes:
      fine structure and content of sodium and potassium of the midgut epithelium of
      the larva of Tenebrio molitor after withdrawal of the basal lamina by elastase--a
      short note.
AB  - A method is described to separate the epithelial cells of the posterior part of
      the mealworm midgut from their thick basal lamina using elastase. After removal
      of the basal lamina the naked epithelial cells remain connected with each other,
      still forming a midgut tube. The ultrastructural changes observed are enlargement
      of the lateral spaces between the cells and simultaneous destruction of
      junctional structures other than desmosomes and tight junctions. This enlargement
      is most probably due to shrinkage of the epithelial cells as a consequence of
      osmotic stress, which the cells normally seem to be protected against by the
      basal lamina. The content of sodium and potassium in the epithelium is not
      influenced by the elastase treatment, indicating that the midgut tube stays alive
      with intact plasma membranes.

PMID- 18620189
TI  - Ultrastructure and development of the extensible abdominal intersegmental
      membranes of the female migratory locust.
AB  - The cuticle of the retracted extensible membrane of the female locust is 300
      microm thick and below its highly folded epicuticle there is a zone (5 microm
      thick) of helicoidally oriented laminae of microfibrils (lamellae), an elastomer
      layer (180 microm thick) of microfibrils with no preferred orientation and a
      subcuticular zone (1 microm thick). The epidermal cell layer has an extensive
      system of junctional specializations and pore canals traverse the cuticle to the
      helicoidally oriented lamellae. In the newly ecdysed adult the elastomer layer is
      absent and the helicoidally oriented lamellae are incomplete. Essentially the
      membrane consists of an elastomer layer contained between two stable layers cross
      linked by pore canals, one to the other. When in the plasticized state the
      membrane combines low stiffness with high extensibility and during extension the
      elastomer layer flows. Recovery is effected by muscles and when the two stable
      layers have returned to their unstretched states the fluid elastomer is again
      evenly distributed. There is an increase in the water content and in the volume
      of the cuticle when it is fully extended. The ultrastructure of the extensible
      membrane is compared with those of the inextensible membranes from male and
      female locusts.

PMID- 18620190
TI  - Histochemical studies of uric acid in some insects. I. Storage in the fat body of
      Periplaneta americana and the action of the symbiotic bacteria.
AB  - An improved histochemical method for uric acid consists in precipitation as
      silver magnesium urate combined with fixation of the tissues in
      formol/glutaraldehyde followed by argentaffin reaction with silver nitrate
      buffered with "tris" to pH 9.5. This reveals urates both in solid deposits and in
      solution in the tissues. Polyphenols concerned in sclerotin formation also react.
      In Periplaneta, uric acid synthesized in the trophocytes is carried by
      intracellular and intercellular channels to form the intercellular deposits of
      solid spheres. The symbiotic bacteria in the mycetocytes in contact with the
      deposits appear to metabolize the uric acid and they disperse and eliminate the
      deposits.

PMID- 18620191
TI  - Histochemical studies of uric acid in some insects. 2. Uric acid and polyphenols
      in the fat body.
AB  - It is recalled that in the larva of Aedes aegypti, starved after a rich protein
      diet, uric acid is formed and accumulates in the fat body, not as solid spheres
      but in high concentration in aqueous vacuoles. In the mature larva of Celliphora
      vicina which has finished feeding and is settling down to form the puparium, the
      fat body at first contains no argentaffin deposits. During the following 2 or 3
      days, argentaffin material appears in the form of amber or brown vesicles and
      black granules of all sizes. Some of this material remains in the fat body cells;
      but a large part, presumably polyphenols, is discharged from the cells so that
      finally all the amber staining disappears and only black granules remain. During
      this transfer the epidermal cells become charged with sclerotin precursors, which
      are transferred into the outer part of the cuticle to form the puparium. The
      stored uric acid remains in the fat body and is dispersed during adult
      development and ultimately excreted.

PMID- 18620192
TI  - Internal extraocular photoreceptors in a dipteran insect.
AB  - Within the head capsule of the moth-fly Psychoda cinerea, underlying each of the
      two compound eyes, are two internal ocelli of different sizes. There are seven
      photoreceptor cells in Ocellus I and two in Ocellus II. The internal Ocellus I
      appears clearly different from the retina of the compound eye, by different
      rhabdom structure, different size of pigment granules and different stability of
      these pigments to solvents. Ocellus II does not contain any pigment granules. The
      physiological activity of these photoreceptors is indicated by their well
      developed axons, the rhabdom structure, organelles produced by membrane
      reorganization, and adaptation phenomena. The internal ocelli are former larval
      stemmata that have been displaced inward during metamorphosis. Presumably they
      have a stimulatory action on the CNS, in analogy with the dorsal ocelli, which
      are lacking in Psychoda. It is plausible to credit the internal ocelli with a
      photosensitive role in the functional complex of pacemakers and circadian rhythm.

PMID- 18620193
TI  - Diffusion barriers in silkmoth sensory epithelia: application of lanthanum tracer
      to olfactory sensilla of Antheraea polyphemus and Bombyx mori.
AB  - The distribution of diffusion barriers in silkmoth olfactory sensilla has been
      investigated with ionic lanthanum. The tracer was applied from the apical side of
      the sensory epithelium by first pinching off the hair tips and then dipping the
      antennal branches into the La(NO(3))(3) solution. The tracer neither passed the
      apical septate junctions between the dendrite and the thecogen cell nor those
      between thecogen, trichogen, and tormogen cells, nor the tight contact between
      the apical membrane of the tormogen cell and the cuticle. After perfusing the
      hemolymph space with La(NO(3))(3) solution, the tracer was found in the clefts
      between the thecogen, trichogen, tormogen, and epidermis cells, but not in those
      between the receptor cells and the thecogen cell, or between the axon and the
      glial envelope. Lanthanum neither entered the receptor-lymph space nor the
      subcuticular space. Therefore, (i) receptor-lymph space, subcuticular space, and
      hemolymph space are isolated from each other, and (ii) the cleft between thecogen
      and sensory cell is separated from the hemolymph as well as from the receptor
      lymph spaces. Furthermore, the results indicate that pleated septate junctions
      form the diffusion barriers in silkmoth olfactory sensilla.

PMID- 18620194
TI  - Oriented spermatozoa in the spermatophore of the palaemonid shrimp, Macrobrachium
      rosenbergii.
AB  - Estimates of the degree of orientation of spermatozoa within spermatophores of
      the freshwater shrimp, Macrobrachium rosenbergii, were made using electron
      micrographs of ultrathin sections cut transverse and parallel to the longitudinal
      axis of the spermatophores. Counts of the total number of longitudinal and non
      longitudinal profiles of sperm spikes in transverse sections of spermatophores
      indicated that 67% of the spermatozoa were oriented with their spikes
      approximately perpendicular to the long axis of the spermatophore. In
      longitudinal sections, approximately 30% of the sperm spike profiles were
      oriented parallel to the longitudinal axis of the spermatophore, leaving
      approximately 70% of the profiles oriented in planes not parallel to the
      longitudinal spermatophore axis. Stereologic analyses based on the number of
      intersections of longitudinally sectioned sperm spike profiles per unit length of
      test lines placed over photographic images of ultrathin sections cut in both
      transverse and longitudinal planes of spermatophores gave a Saltykov
      approximation of 0.607, favoring the view that the spermatozoa were oriented with
      their spikes perpendicular to the long axis of the spermatophore. This
      orientation brings many of the sperm bases approximately parallel to the surface
      of the spermatophore, an orientation which may facilitate normal sperm-egg
      interaction during fertilization in this species.

PMID- 18620195
TI  - Proteins induced in Bacillus subtilis infected with bacteriophage phi29.
AB  - Bacteriophage phi29 induces, in UV-irradiated B. subtilis, the synthesis of 12
      non-structural proteins as well as the 7 structural polypeptides which form the
      viral particle. The molecular weight of the nonstructural polypeptides amounts to
      180,000 daltons; if all these proteins are phage-coded, this corresponds to about
      30% of the information content of phi29 DNA. The phage-induced polypeptides can
      be classified as early and late proteins, according with the time of their
      appearance after infection. All the structural proteins as well as three
      nonstructural proteins are late proteins. The remaining nonstructural proteins
      appear early after infection.

PMID- 18620196
TI  - A comparative study of ciliary differentiations in the branchial stigmata of
      ascidians.
AB  - In a correlated thin sectioning and freeze-fracturing study, we have examined
      species belonging to the orders of the ascidian class: Stolidobranchiata
      (Botryllus schlosseri, Botrylloides leachi, Molgula socialis, Styela plicata),
      Phlebobranchiata (Ascidiella aspersa, Phallusia ingeria, Ciona intestinalis) and
      Aplousobranchiata (Clavelina lepadiformis). Though the branchial basket varies in
      the complexity and filtration efficiency in the three orders, the ciliated
      epithelia aroand the stigmata contain a common pattern of organization; seven
      rows of flattened cells, each bearing a single row of long cilia flanked by a
      single row of microvilli. All the species examined possess ciliary
      specializations represented by: (a) bridges connecting doublets number 5 and 6 as
      well as 9.1 and 2; (b) dense material lying between the above mentioned axonemal
      doublets (5-6 and 1-2) and the ciliary membrane, sometimes in the shape of
      longitudinal strands or often as lines of dots; (c) a fuzzy coat protruding from
      the ciliary membrane, consisting of tufts or scattered filaments; (d)
      intramembrane particles (IMPs) associated with the P-face of the membrane, often
      arranged in clusters and orderly alignments related to the anderlying axonemal
      doublets; these IMPs decorate the opposite sides of each cilium facing the
      adjacent cilia forming the ciliary rows of adjacent cells and are absent on the
      lateral sides. The stigmatal cilia propel water through the stigmata and their
      effective strokes follow a line at right angles to the row of cilia in each cell.
      The usual direction of the effective stroke is toward doublets 5-6. It is
      possible, therefore, to refer to structure in relation to the ciliary beat cycle.
      The importance of these specializations is unknown, but the structures appear to
      vary in the different species. A correlation between the richness of the
      specializations and the complexity of the branchial basket was not evidenced. It
      was suggested that the ciliary specializations relate to the peculiar
      organization of the stigmatal margin and that all are involved in the regulation
      of the ciliary activity.

PMID- 18620197
TI  - Epithelial cell types of the primary ureter of Helix aspersa: Ultrastructural and
      cytochemical characteristics.
AB  - The present study describes the morphological characteristics which determine the
      structural polarity of the principal and ciliated cells in the primary ureter
      epithelium of Helix aspersa. These characteristics are analysed on the basis of
      the function performed by both cell types. The presence of paniculate glycogen
      and the location of glycoconjugates associated with cell membranes of the
      epithelial cells is revealed by the method of Thiery.

PMID- 18620198
TI  - Histochemical studies of uric acid in some insects. 3. Excretion of uric acid by
      the malpighian tubules in Calliphora vicina and Rhodnius prolixus.
AB  - In adult Calliphora uric acid is excreted throughout the Malpighian tubules.
      Histochemical preparations for the light microscope show uric acid passing
      through the cells and forming crystalline spheres in immediate contact with the
      microvilli. Uric acid appears to be synthesized and discharged into the
      haemolymph by the fat body cells. In Rhodnius there is no visible uric acid in
      the cells or lumen of the upper segment of the tubule (two-thirds of the total
      length of the tubule) apart from occasional deposits in the basal lamina. All
      uric acid excretion depends on the lower segment. Electron micrographs after
      argentaffin staining show high concentration of uric acid in the cytoplasm below
      the basal lamina (which also contains uric acid deposits). Uric acid is visible
      throughout the cell, particularly aroand the mitochondria; it is absent from the
      infolded plasma membrane and from all vacuoles. At the lumen there is a
      concentrated deposit of uric acid immediately beyond the plasma membrane. The
      uric acid particles unite with particles of unstained matrix material to form
      crystalline spheres. The fat body shows active synthesis of uric acid which is
      discharged by the cells into the intercellular channels and so to the basal
      lamina through which it passes into the haemolymph. As judged by histochemical
      preparations the haemolymph contains a high concentration of uric acid, very
      variable in different sites. Likewise large variations in uric acid secretion
      occur in different parts of the fat body.

PMID- 18620199
TI  - The cercal sensilla of the blowfly Lucilia cuprina. I. Structure of the sockets
      and distal dendritic regions.
AB  - The functions of the gustatory, olfactory, touch and stress receptors on the
      cerci of Lucilia cuprina Wied. (Diptera: Calliphoridae) are apparent from the
      morphology of their distal dendritic segments and associated cuticular
      structures. Each trichoid mechanoreceptor has a dendrite containing a tubular
      body at the base of the hairshaft. The suspension fibres and socket septum may be
      involved in transmitting a stimulus to the dendrite terminal and restoring the
      hair to its resting position. The campaniform sensilla are considered as trichoid
      mechanoreceptors with reduced hair shafts and socket structures, reflected in
      fusion of the suspension fibres into the inner cuticle of the dome and loss of
      the socket septum. Fusion and reduction of the socket structures is also apparent
      at the bases of the olfactory pegs. They differ from typical antennal olfactory
      sensilla in having a flexible socket and relatively thick walls; features which
      may protect them from damage during ovipositor probing of potential oviposition
      substrates. The two types of cereal gustatory sensilla differ in their complement
      of chemosensory dendrites, one has three, the other four, the latter type also
      has a mechanoreceptive dendrite at the base of the hair shaft. Both types have
      socket structures resembling those of the trichoid mechanoreceptors.

PMID- 18620200
TI  - The very rapid induction of filopodia in insect cells.
AB  - Many insect cells, including epidermis, fat body, ocnocytcs and pericardial
      cells, can very easily be induced to form long fine processes or filopodia.
      Filopodia contain microfilaments hut differ from epidermal feet in lacking
      microtubules and in having a much smaller and uniform diameter. Although they may
      be 10-30 mum long they are less than 0.1 mum wide. They often form straight
      connections like guy-ropes between their origins and their tips, and when freed
      from their surface attachments they may contract into helices, as though capable
      of generating tension. The basal lamina helps to keep the basal surfaces of
      epidermal cells together. In Rhodnius epidermis, filopodia form only seconds
      after its removal. They arise at the cell margins and extend to distant part of
      neighbouring cells where they adhere particularly at their tips. Such filopodia
      retract and disappear in 20-60 min with the reformation of the basal lamina as
      though they have functioned to pull neighbouring cells back together. In Calpodes
      epidermis, filopodia form from the lateral faces as well as the cell margins
      after trypsin digestion of desmosomes and hemidesmosomes. The observations
      suggest that filopodia are induced in response to cell separation and function to
      restore cell to cell continuity. Filopodia also form in the normal course of
      development where cells separate prior to their rearrangement to make new tissues
      as in epidermal and fat body metamorphosis. Filopodia are probably ubiquitous
      agents for the sensing and movement of cells relative to one another in tissue
      morphogenesis.

PMID- 18620202
TI  - Morphometry of transport tissues in a freshwater crustacean.
AB  - Gills and fenestra dorsalis of the syncarid crustacean Allanaspides helonomus
      were examined with the electron microscope. Their epithelia were characterized
      using morphometric measurement, with a view to assessing potential for ion
      transport and respiratory activity. The results obtained show distinctions
      between the paired gills and allow the possibility that one gill of each pair is
      respiratory and the other osmoregulatory. The fenestra dorsalis has been
      tentatively assigned a transport function, although the nature of its transport
      load remains uncertain. The detailed morphometric analysis provided useful
      insights into the nature of the tissues studied.

PMID- 18620201
TI  - Replication of Sindbis virus. III. An electron microscopic study of virus
      maturation using the surface replica technique.
AB  - We have examined surface replicas of chick embryo cells infected with Sindbis
      virus. In some cells the virus buds over extensive areas of the cell surface,
      although there are areas where budding virus is clustered and other regions
      almost devoid of budding figures. In other cells, virus budding occurs primarily
      or exclusively at the periphery of the monolayer cells. Budding in these cells
      often occurs in long processes extending from the cell, which have widths from
      one to several virion diameters and lengths up to 7 microm. These processes have
      also been examined by means of thin sections to visualize their internal
      features, especially the presence of nucleocapsids in the process of budding.

PMID- 18620203
TI  - The feeding apparatus of a chitinivorous ciliate.
AB  - The chitinivorous ciliate Ascophrys, an ectosymbiont of the shrimp Palaemon
      serratus, is enclosed by a thick cyst wall except for a ventral hiatus exposing a
      circular area of exoskeleton to the interior of the cyst. The exoskeleton
      underlying the cyst wall remains intact, but the circular area of exoskeleton is
      dissolved enzymatically and ingested. The feeding ciliate forms a cavity in the
      exoskeleton into which it sinks. Its complex oral apparatus resembles a pump
      encircled by cytoplasm containing Golgi and high concentrations of coated
      vesicles that join pellicular pores between cilia. The ingestive apparatus is
      formed of microtubular lamellae that originate in the midplane of the body,
      descend toward a coated membrane on the surface, and ascend again as a lamellar
      lining to a complex food tube that ends in the middle of the body surrounded by
      food vacuoles. The cytoplasm enclosed between the descending lamellae and the
      food tube is crowded with membrane organelles that recycle as food vacuole
      membranes at the coated membrane. We hypothesize that vacuoles containing
      dissolved exoskeleton are drawn up into the oral tube and are released into the
      cytoplasm at the terminus of the tube, where their contents are concentrated and
      excess vacuolar membrane collapsed into membrane organelles.

PMID- 18620204
TI  - A light and electron microscopic study of a new species of centroheliozoon,
      Chlamydaster fimbriatus.
AB  - The centroheliozoon Chlamydaster fimbriatus n.sp. has been studied in culture by
      light and electron microscopy. The cell body is surrounded by a fimbriated mucus
      envelope through which axopods extend. Each cell contains two or three
      contractile vacuoles and an eccentrically located nucleus with a single
      nucleolus. The cells have typical centroheliozoan characteristics such as a
      centroplast with a trilamellate disc, mitochondria with ribbon-like cristae, ball
      and-cone kinetocysts, and a peripheral lacunar system. The axopodial axonemes
      possess a single hexagon of six microtubules. The genus is defined to include
      only centroheliozoa with a mucus coat. C. fimbriatus differs from the only other
      species recognized in this genus (C. laciniatus and C. sterni) in its size and
      number of arms. This is the first ultrastructural account of a species of the
      genus Chlamydaster.

PMID- 18620205
TI  - Ultrastructural features of oogenesis in a free-living marine Platyhelminth,
      Vorticeros luteum.
AB  - The female gonad of the prolecithophoran turbellarian Voticeros luteum has a
      heterocellular organization as is typical in the neoophoran Platyhelminthes. It
      is composed of an ovarian and a vitellarian area that are not well separated from
      one another and from the surrounding tissues by a tunica. Each oocyte during
      maturation becomes completely surrounded by a single accessory cell whose
      function has been hypothesized on the basis of the present investigation. The
      main feature in oocyte differentiation appears to be the synthesis and
      accumulation of small electron-dense inclusions; these are about 1-2 microm in
      size, are elaborated by the Golgi apparatus and have a content which reacts
      partially to the cytochemical test for polyphenols. The genesis, composition and
      cortical localization of the inclusions suggest that they could be homologous to
      the egg-shell granules present in the oocytes of 'archoophoran' species. A
      comparative analysis and discussion of the oocyte inclusions observed to date in
      other turbellarians is undertaken and the hypothetical use of these structures as
      characters providing some new insights in clarifying the phylogenetic
      relationships among free-living Platyhelminthes is finally discussed.

PMID- 18620206
TI  - Role of the nephridia in the elimination of foreign cells from the coelomic fluid
      of two polychaete annelids, with observations on the structure of the nephridia.
AB  - Formalinized sheep red blood cells and living bacteria (Serratia marinorubra) are
      rapidly phagocytosed. When infected into Arenicola marina and Neoamphitrite
      figulus. Phagocytes clump but later disperse. After sheep red cells have been
      taken up by phagocytes they migrate through the nephridial cells into the lumen.
      After bacteria have been taken up by the phagocytes they also clump and again
      later disperse but they are not found within the nephridial cell walls probably
      because the bacteria are effectively eliminated by the phagocytes. Formalinized
      red cells are probably indigestible and such particles can only be eliminated by
      active migration of the phagocytes to the exterior, or are sequestered or, more
      rarely, encapsulated. Loss of either red cells or bacteria directly through the
      nephridia is no more than can be accounted for by normal urine flow.

PMID- 18620207
TI  - Cell junctions in amphioxus (Cephalochordata): a thin section and freeze-fracture
      study.
AB  - Tissues from the epidermis, alimentary tract and notochord of the cephalochordate
      Branchiostoma lanceolatum have been examined in both thin sections and freeze
      fracture replicas to ascertain the nature of the intercellular junctions that
      characterize their cell borders. The columnar epithelial cells from the branchial
      chamber (pharynx), as well as from the anterior and posterior intestine, all
      feature cilia and microvilli on their luminal surfaces. However, their lateral
      surfaces exhibit zonulae adhaerentes only. No gap junctions have been observed,
      nor any tight junctions (as are a feature of the gut of urochordates and higher
      vertebrates), nor unequivocal septate junctions (as are typical of the gut of
      invertebrates). The basal intercellular borders are likewise held together by
      zonulae adhaerentes while hemidesmosomes occur along the basal surface where the
      cells abut against the basal lamina. The lateral cell surfaces, where the
      adhesive junctions occur, at both luminal and basal borders, do not exhibit any
      specialized arrangement of intramembrane particles (IMPs), as visualized by
      freeze-fracture. The IMPs are scattered at random over the cell membranes, being
      particularly prevalent on the P-face. The only distinctive IMPs arrays are those
      found on the ciliary shafts in the form of ciliary necklaces and IMP clusters.
      With regard to these ciliary modifications, cephalochordates closely resemble the
      cells of the branchial tract of ascidians (urochordates). However, the absence of
      distinct junctions other than zonulae adhaerentes makes them exceptions to the
      situation generally encountered in both vertebrates and urochordates, as well as
      in the invertebrates. Infiltration with tracers such as lanthanum corroborates
      this finding; the lanthanum fills the extracellular spaces between the cells of
      the intestine since there are no junctions present to restrict its entry or to
      act even as a partial barrier. Junctions are likewise absent from the membranes
      of the notochord; the membranes of its lamellae and vesicles exhibit irregular
      clusters of IMPs which may be related to the association between the membranes
      and the notochordal filaments. Epidermis and glial cells from the nervous system
      possess extensive desmosomal-like associations or zonulae adhaerentes, but no
      other junctional type is obvious in thin sections, apart from very occasional
      cross-striations deemed by some previous investigators to represent 'poorly
      developed' septate junctions.

PMID- 18620208
TI  - A novel occluding junction which lacks membrane fusion in insect testis.
AB  - Spermatocysts develop within the lumina of the lepidopteran testis. Each
      spermatocyst contains a clone of maturing germ cells which are separated from the
      fluid in the testicular lumen by a layer of somatic envelope cells. A blood
      testis barrier is located at the level of the somatic envelope cells. We used
      macromolecular tracers horseradish peroxidase (applied before fixation) and
      ruthenium red (applied during fixation) with thin sections and freeze-fracture
      replicas to study the nature of this barrier in spermatocysts of the tobacco
      budworm, Heliothis virescens. Movement of the tracers into the spermatocysts was
      blocked by a structure at the outer edge of the septate junctions which join the
      spermatocyst envelope cells. In freeze-fracture replicas there was a P-face ridge
      or an E-face groove in this location. The ridge/groove appeared similar to a
      single-stranded vertebrate tight junction. Unlike tight junctions, however, there
      was no fusion or even close apposition of adjacent cell membranes in this
      location. We conclude, therefore, that a novel type of occluding junction was the
      barrier to paracellular movement of macromolecules in Heliothis spermatocysts.

PMID- 18620209
TI  - Quantitative evidence for merocrine secretion in insect midgut cells.
AB  - The occurrence of apical extrusions from cells has been observed on a large
      number of occasions in a wide variety of histological investigations. But whether
      the extrusions observed are a normal physiological event or are artefacts of the
      experimental procedures adopted has been the subject of much controversy. Lehane
      (1976a) described the extrusion of apical portions of the opaque zone midgut
      cells of Stomoxys calcitrans which contained large numbers of storage granules
      (merocrine secretion). This process involved the cell in the loss of cytoplasm,
      mitochondria and membranes as well as secretory products. If merocrine secretion
      is a normal physiological event rather than a fixation artefact then large falls
      should occur in the quantities of these components in the cell following the
      secretion burst. Using stereological methods the opaque zone cells were
      quantitatively described before and after the period in which merocrine secretion
      occurs (using these timings any possibility of producing apical extrusions as
      fixation artefacts was avoided). The results are entirely consistent with
      merocrine secretion having occurred. The volume of the cytoplasm falls by 23.74%,
      mitochondria by 30.55% and the total area of membrane in the cell by 32.59%.

PMID- 18620210
TI  - The final stages of wing development in Drosophila melanogaster.
AB  - A brief description is given of the behavioural changes in Drosophila
      melanogaster at the time of eclosion and wing expansion. The developmental
      changes in the wing during this period are classified into four stages (0-III).
      Details of changes in the morphology of both the cuticle and the wing epidermal
      cells are given using both light and electron microscopy. It was found that the
      breakdown of the wing epidermis is initiated before wing expansion starts. The
      results obtained for Drosophila are compared with those for other insect species.

PMID- 18620211
TI  - Change of form of septate and gap junctions during development of the insect
      midgut.
AB  - In insects, smooth septate junctions join cells derived from the embryonic
      midgut, and pleated septate junctions are found in all other tissues. Relatively
      little is known about either type of septate junction or the relationship between
      them, but they have been treated as two different junctions in the literature.
      The gap junctions which are associated with these septate junctions also differ.
      Crystalline gap junctions are found in the midgut, associated with smooth septate
      junctions, and irregular gap junctions are found in tissues where pleated septate
      junctions are located. We have examined the development of smooth septate
      junctions and crystalline gap junctions and the relationship between them, by
      studying the embryogenesis of the midgut in Manduca sexta (tobacco hornworm). At
      56 hr of development (hatching is at 104 hr) pleated septate junctions and
      irregular gap junctions joined the midgut epithelial cells. At 65 hr, the septate
      junctions had disappeared, but gap junctions persisted. At 70 hr, smooth septate
      junctions had replaced the earlier pleated septate junctions and gap junctions
      associated with these smooth septate junctions were often of the crystalline
      form. In later embryos, the smooth septate junctions matured and enlarged, while
      all gap junctions became crystalline in form.

PMID- 18620212
TI  - Ultrastructure of the anal organ of Drosophila larva with reference to ion
      transport.
AB  - The ultrastructure of the anal organ of the full-grown larva of Drosophila
      melanogaster is described. The thin cuticle is characterized by epicuticular
      depressions which contain particulate material. In AgNO(3)-treated larvae, silver
      grains tend to penetrate the cuticle at the epicuticular depressions. At the
      basal surface, the epithelial cells exhibit narrow, parallel membrane infoldings
      which bear a particulate coat on the cytoplasmic surface. The infoldings are also
      attached around the cytoplasmic surface of endocuticular tubercles, thereby
      greatly increasing the absorptive surface area. At the apical surface, the
      membrane invaginations, which are closely associated with mitochondria,
      anastomose freely and extend deeply into the cytoplasm. The lateral membranes are
      linked by desmosomes and septate junctions. They are highly folded, are closely
      associated with mitochondria, and enclose intercellular channels and spaces. The
      epithelial cells are rich in mitochondria, glycogen particles and tracheoles.
      Numerous vesicles, multivesicular bodies, lysosome-like dense bodies and sparse
      endoplasmic reticulum are found in the cytoplasm. In concentrated medium, the
      epithelial cells show complete absence of the membrane infoldings and
      invaginations and reduction in the number of mitochondria. The ultrastructural
      features of the anal organ are consistent with its function in ion transport.

PMID- 18620213
TI  - Enzyme effects on the connective tissues of an insect central nervous system.
AB  - The effect of various enzymes on the two connective tissue matrices of the
      cockroach central nervous system were investigated. Removal of the neural
      lamella, using collagenase, allows some of the cells which form the perineurium
      to pull out of this cell layer but the perineurial bracelet cells maintain an
      intact blood-brain barrier. Incubation of the nerve cord with hyaluronidase has
      little or no effect on the neural lamella and allows the selective removal of the
      matrix from the glial lacunar system. Partial removal of this matrix appears to
      have little effect on the ability of the axons to conduct action potentials at
      high frequencies. In addition to this difference in susceptibility of the neural
      lamella and lacunar matrices to different enzymes, there appears to be a
      difference between the lacunar matrix of the connectives and of the ganglia, the
      latter being more resistant to enzyme attack. There is no such difference in the
      neural lamella covering the ganglia and connectives.

PMID- 18620214
TI  - Neutrophil-endothelial interactions: Modulation of neutrophil activation
      responses by endothelial cells.
AB  - There is controversy concerning whether intravascular activation of neutrophils
      during acute inflammation injures contiguous endothelial cells in vivo. Several
      physiologic defense mechanisms tend to limit such injury. In this paper we have
      examined evidence for one of these putative protective mechanisms: endothelial
      cell modulation of the activation responses of neutrophils during adherence and
      diapedesis. In vitro, endothelial cells co-incubated with neutrophils inhibit the
      release of superoxide anion when stimulated by receptor-mediated activators. The
      possible mechanisms include contact-linked down-regulation of neutrophil
      activation, the release from endothelial cells of soluble mediators which
      attenuate neutrophil activation responses, and the presence of free radical
      scavengers in endothelial cells which are active at the interface between
      endothelial cells and adherent neutrophils. There may be a broad spectrum of
      mechanisms by which intercellular interactions protect the lining cells of the
      vascular lumen from 'inadvertent' destruction by phagocytes which become
      activated while in an intravascular location.

PMID- 18620215
TI  - Supercoil of collagen fibrils in the integument of Alvinella, an abyssal annelid.
AB  - The polychaete annelid Alvinella pompejana was discovered near the hydrothermal
      vents, recently explored in the Eastern Pacific Ocean. This worm is protected by
      a cuticle deeply transformed over certain areas of the body and some changes are
      due to the presence of a very special bacterial flora. The present work however
      deals mainly with the supercoiled collagen fibrils, which are well visualized in
      thin sections observed by transmission electron microscopy. This character
      strongly differentiates this species from other annelids and worms in general,
      the cuticle of which includes straight and apparently non-coiled collagen
      fibrils. This indicates that fibrils are extensible in Alvinella, possibly under
      physiological conditions, and that internal pressure and local volume variations
      are regulated according to principles which depart from what is recognized in
      other worms, where cuticular fibrils are considered as inextensible. Possible
      models of this cuticle are discussed and particularly aspects which show a
      relationship with certain liquid crystals. Very different factors may be involved
      in morphogenesis of such cuticles: microvilli distribution, self-assembly of
      collagen fibrils, mechanical constraints. An appendix recalls some classical data
      on worm cuticle geometry and presents an estimate of volume variations resulting
      from coiling of fibrils.

PMID- 18620216
TI  - The head cartilage of cephalopods. I. Architecture and ultrastructure of the
      extracellular matrix.
AB  - The morphology of head cartilage of the cephalopods Sepia officinalis and Octopus
      vulgaris has been studied on samples fixed and embedded for light- and electron
      microscopy and on fresh frozen sections viewed by polarizing microscopy. The
      organization of extracellular matrix (ECM) varies in different regions of the
      head cartilage. Superficial zones are made up of densely packed collagenous
      laminae parallel to the cartilage surface, while radially arranged laminae form a
      deeper zone where territorial and interterritorial areas are present. A compact
      arrangement of banded collagen fibrils (10-25 nm in diameter) forms the laminae
      of the superficial zones and of the interterritorial areas; a loose three
      dimensional network of fibrils (10-20 nm) with many proteoglycan aggregates forms
      the territorial areas. A pericellular matrix surrounds the bodies of extremely
      branched territorial chondrocytes. Peculiar anchoring devices (ADs) are dispersed
      with variable orientation within the ECM. A perichondrium is present, but often
      connectival and muscular bundles are fused with the superficial layers of
      cartilage. Some vessels were also observed within the superficial inner zone and
      clusters of hemocyanin molecules were demonstrated both in the ECM and in some
      cells. The cephalopod head cartilage seems to share some morphological
      characteristics with both hyaline cartilage and bone tissue of vertebrates.

PMID- 18620217
TI  - The scent glands of the male south american locust Schistocerca cancellata, an
      electron microscope study.
AB  - The male South American locust, Schistocerca cancellata, emits a strong aromatic
      scent at the time of maturation. This aroma is characteristic of mature adult
      males living in crowded conditions. In isolated males and in females it is
      perceptible but faint, while nymphs emit no scent at all. Since dermal glands are
      numerous in the mature adult but much rarer in nymphs, young imagos and females,
      it seems likely that the scent is associated with these glands. The scent seems
      to be a maturation-pheromone, stored and released by these dermal glands. Each
      gland consists of a gland cell and a duct cell (type 3 gland in the
      classification of Noirot and Quennedey, (1974)). Each gland cell has a single end
      apparatus consisting of an oblong cavity limited by the projecting tips of
      densely packed microvilli. A duct, dilated to form three successive bulbosities
      at its distal end, opens in the cavity from which it conveys the secretion to the
      outside. A network of fibrillar material anchors the duct to the cavity.
      Reproductive synchrony, beneficial in social insects, seems to be achieved in
      locusts by the aromatic pheromone released by the glands at the time of
      maturation.

PMID- 18620218
TI  - Insect cuticular growth layers seen under the scanning electron microscope: A new
      display method.
AB  - The scanning electron microscope (SEM) is demonstrated as a useful tool in the
      study of insect cuticular growth layers. The helicoids present in the endocuticle
      are shown to be comprised of discrete chitin fibrils, orientated in a staggered
      manner. Surface relief is used to explain the appearance of daily growth layer
      images under the SEM, the bulk of this work being performed on the short-horned
      grasshopper, Romalea microptera.

PMID- 18620219
TI  - Ultrastructure of the excretory system of the marine nematode Monhystera
      disjuncta.
AB  - The excretory system of Monhystera disjuncta is a single ventral gland in the
      pharyngo-intestinal region. Its ultrastructural morphology is described. The
      posterior part is swollen, contains the nucleus and many secretory granules. This
      part gradually narrows anteriorly to form the cell neck, in the apical part of
      which a valve structure is differentiated. This pear-shaped valve structure opens
      into a cuticular duct which is embedded in an accompanying cytoplasmic sheath.
      The cuticular duct opens to the exterior by a pore between the two subventral
      inner labial papillae.

PMID- 18620220
TI  - Receptor-mediated endocytosis of a chemoreceptor involved in triggering the
      discharge of cnidae in a sea anemone tentacle.
AB  - Collodial gold coated with the glycoprotein, bovine submaxillary mucin (BSM
      gold), was used to localize chemoreceptors known to be involved in triggering the
      discharge of cnidae in sea anemones. BSM-gold binds exclusively at the apical
      surface of the supporting cell, the cell adjacent to the cnidocyte (Watson and
      Hessinger, 1986). Subsequent to binding, BSM-gold is internalized into endosomes
      and then translocated to multivesicular bodies (MVBs) and lysosomes. At cold
      temperature (4 degrees C), BSM-gold appears in endosomes near the surface of the
      cell but not in endosomes located more medially in the cell, nor in MVBs or
      lysosomes. The kinetics and sequence of intracellular translocation of BSM-gold
      were studied by fixing animals at various intervals following incubation in BSM
      gold. Unlike that for supporting cells adjacent to non-cnidocytes, the amount of
      gold at the surface of supporting cells adjacent to penetrant cnidocytes does not
      seem to change despite considerable internalization of the mucin-probe.
      Apparently, free receptors replace receptor-ligand complexes in a one-for-one
      fashion in these cells.

PMID- 18620221
TI  - The fibrous system of the extracellular matrix of Podocoryne carnea and its
      degradation by the subumbrellar plate endoderm demonstrated by a monoclonal
      antibody.
AB  - Homogenized fragments of crude umbrellar material of the hydromedusa Podocoryne
      carnea was injected into BALB/c mice. The immunization resulted in the isolation
      of a monoclonal antibody designated 3A1 which specifically binds to fibrils in
      the mesogloeal extracellular matrix (ECM) of hydromedusae. In vivo, the
      architecture and the ultrastructure of the fibrous system in the outer mesogloea
      (outer ECM) of Podocoryne carnea, and its degradation under in vitro conditions
      have been described by morphological and immunological criteria. In vivo, 120-150
      A thick, striated fibrils (with periodicities up to 50 nm) form a
      threedimensional network which fills in the entire outer ECM. Vertical fibers (up
      to 150 nm in diameter) penetrate the three-dimensional network and branch at the
      subumbrellar and the exumbrellar side. The vertical fibers show uniform
      distribution over the entire outer ECM. The branches impinge on a dense matrix
      (about 30 nm in thickness) covering the exumbrellar and subumbrellar surface. In
      vitro, the fibrillar system does not alter in its basic pattern, neither in
      isolated outer ECM, nor in portions of outer ECM which is either covered by the
      exumbrella, or which is attached to both: the exumbrella at the outside, and the
      subumbrellar plate endoderm at the inner side. After removal of the exumbrellar
      cells in the latter portions, a characteristic pattern of selective degradation
      of the outer ECM by the endodermal cells is observed. This process involves three
      distinct steps: an initial extracellular condensation within the ECM fibrillar
      network, followed by intercellular internalization of the fibrillar elements and
      subsequent endocytosis of ECM material. The first step immediately follows the
      removeal procedure of the exumbrellar cells and is completed within minutes. This
      process cannot be interrupted by dihydrocytochalasin B (H(2)CB). The second step
      lasts 24-48 hr, is mediated by cell mechanisms, and can be stopped by H(2)CB. The
      third step is a slow process (of up to 14 days). It involves intercellular
      degradation of fibrillar material, endocytosis, and completion of digestion
      within lysosomes.

PMID- 18620222
TI  - Evidence for the existence of microtubule protein in the extracellular space of
      marine sponges.
AB  - The medulla region of sponges (= mesohyl) is only rarely dispersed with cells
      (approximately 25% of the total tissue volume). In vivo studies with a series of
      anti-cytoskeletal drugs revealed that taxol caused a significant contraction of
      intact specimens. Therefore, we investigated the possibility that microtubules
      are one component of the dynamic extracellular network in sponges, especially in
      the mesohyl. Using the sponge Geodia cydonium we found that most cells are not
      intracellulary stained in indirect immunofluorescence microscopy. However, all
      cells were brightly stained by the monoclonal antibody (mAb) at their plasma
      membranes. After incubating cryostat sections with a buffer, containing ATP,
      large (length up to 75 mum) aster- to filamentous-like structures became visible
      in the extracellular space of the mesohyl region. By three cycles of assembly and
      disassembly microtubules could be isolated from the extracellular material which
      were composed of alpha- and beta-tubulin (M(r): 55,000), several polypeptides
      within the M(r) range 55,000-82,000 (presumably tau proteins) and one protein of
      an M(r) higher than 100,000. Electron microscopical analysis revealed
      morphologically intact microtubules with typical side projections (very probably
      composed of microtubule-associated protein). Some aspects of the possible
      involvement of microtubules in the extracellularly localized displacement and
      motion network are discussed.

PMID- 18620223
TI  - Spider tracheal systems.
AB  - 1. The tracheal structures of spiders belonging to 15 families were investigated.
      Techniques developed primarily for use with insects were used to visualize spider
      tracheae. The tracheae were investigated in whole spiders and with serial
      sections. A macerating agent is described which dissolves the soft-tissues of the
      spiders without harming the tracheae, or decolourizing the injected dye. 2. A
      variety of tracheal systems are illustrated using diagrammatic line-drawings and
      photographs. 3. The variation in the tracheal structures of the spiders
      investigated in this study is discussed, as well as the use of tracheal
      structures in spider classification. Spider tracheae are compared with those of
      insects. 4. A list is given of the major investigations into spider tracheal
      systems this century.

PMID- 18620224
TI  - Ultrastructural shape and three-dimensional organization of the intracuticular
      canal systems in the mineralized cuticle of the green crab Carcinus maenas.
AB  - Two main self-contained canal systems are present in the crab mineralized
      cuticle. The first, or fibre canal system, is constituted by simple, unbranched
      vertical canals containing axially running fibres in close association with
      myoepidermal junctions. The second, or pore canal system, is composed of
      procuticular pore canals and epicuticular channels that prolong the procuticular
      canals. In opposition to widespread opinion, pore canals make up a three
      dimensional branched system extending from the apical plasma membrane of the
      epidermis up to the epicuticle. Branching occurs by projections of lateral
      horizontal from the vertical canals at the lower level of the pigmented layer and
      by innumerable ramifications of epicuticular canals. In agreement with Neville's
      model for insects, vertical procuticular pore canals of crustacean mineralized
      cuticle, and also fibre canals, exhibit a twisted ribbon structure reflecting the
      helicoidal arrangement of the horizontal chitin-protein microfibrils.

PMID- 18620225
TI  - Elaboration and ultrastructural changes in the pore canal system of the
      mineralized cuticle of Carcinus maenas during the moulting cycle.
AB  - Two basic structural components are concerned in the elaboration of the pore
      canal system in the mineralized cuticle of the decapod crab Carcinus maenas:
      tubular cytoplasmic extensions originating from epidermis and vertical fibres.
      These components are present from the moment the first procuticular materials of
      the new cuticle are laid down but their organization varies according to a
      precise schedule during the further moult cycle stages. Cytoplasmic extensions
      form a complicated branching system connecting the epidermal layer with all
      regions of the cullcular compartment, at least transitorily. During the moult
      cycle the prolongation of this cellular system appears to result from two
      concomitant but opposite phenomena. Before ecdysis the growth of cell extensions
      in the proximal cuticular layers prevails over their regression at the distal
      level. During the post-moult period these phenomena are reversed in importance so
      that the pore canal system is without cytoplasmic material as soon as intermoult
      starts. The depositing of vertical fibres takes place in close contact with the
      proximal cell extension plasma membrane, which never bears dense plaques. As
      moult stages progress, they are gradually organized into twisted sheaths that
      persist throughout the intermoult. Incidentally, some fibres invade the pore
      canal lumen freed from cell extensions. Some aspects regarding the fine
      organization, the chemical composition and the functional significance of both
      epidermal tubular extensions or vertical fibres are also discussed in the light
      of previous investigations carried out on crustaceans and in other arthropods.

PMID- 18620226
TI  - Blood cells contribute to glial repair in an insect.
AB  - Using antibodies specific for haemocytes, we have shown that these blood cells
      penetrate the abdominal nervous connectives of the cockroach following selective
      disruption of the glia using the DNA-intercalating drug, ethidium bromide, as a
      glial toxin. Within 4 days post-lesion, the labelled cells formed a mosaic
      beneath the neural lamella and penetrated deeply among the disrupted
      subperineurial glia. These observations confirm that exogenous cells are involved
      in glial repair and support a previous hypothesis that they play critical roles
      in both structural repair and the recruitment of endogenous reactive cells.

PMID- 18620227
TI  - Cell differentiation in the embryonic midgut of the tobacco hornworm, Manduca
      sexta.
AB  - While the larval midgut of Manduca sexta has been intensively studied as a model
      for ion transport, the developmental origins of this organ are poorly understood.
      In our study we have used light and electron microscopy to investigate the
      process of midgut epithelial cell differentiation in the embryo. Our studies were
      confined to the period between 56 and 95 hr of embryonic development (hatching is
      at 101 hr at 25 degrees C), since preliminary studies indicated that all
      morphologically visible differentiation of the midgut epithelium occurs during
      this time. At 56 hr the midgut epithelium is organized into a ragged
      pseudostratified epithelium. Over the next 10 hr, the embryo molts and the midgut
      epithelium takes on a distinctive character in which the future goblet and
      columnar cells can be identified. With further differentiation, closed vesicles
      in the goblet cells expand and subsequently communicate to the outside by way of
      a valve. The columnar cells form numerous microvilli on their apical surfaces
      that extend over the goblet cells. Both cell types form basal folds from a series
      of plasmalemmal invaginations. Differentiation occurs concurrent with a six-fold
      elongation of these cells.

PMID- 18620228
TI  - The muscle of a monogonont rotifer, Trichocerca rattus. II. The central retractor
      muscles.
AB  - This work concerns the ultrastructural characteristics of the two cells of the
      paired, bicellular, central retractor muscles (CRM) of the rotifer Trichocerca
      rattus. By transverse ultrathin serial sections, precise measurements where made
      on the following cytological characteristics: the length, diameter and average
      number by unit surface area for the myofilaments; the percentage of cell volume
      for the myoplasm and mitochondria; and the average number of peripheral elements
      of the sarcoplasmic reticulum (dyads) by unit surface area. These characteristics
      agree with a phasic fibre type for the CRM. The muscular insertions are
      described, as are the junctions between the two cells of each CRM:
      hemidesmosomes, desmosomes and gap junctions. The two symmetrical CRM are coupled
      by a large gap junction between two subcerebral sarcoplasmic processes. Some of
      these processes partially enter the cerebral neuropile; each CRM is innervated at
      this level. The functions of the cytological specializations are discussed in the
      light of the behaviour assumed by the CRM: the retraction of the rotatory
      apparatus in the trunk of T. rattus.

PMID- 18620229
TI  - Different functions of tight junctions in the ascidian branchial basket.
AB  - The stigmatal cells in the branchial basket of ascidians from a number of genera
      have been examined as to the nature and distribution of their intercellular
      junctions. The branchial wall consists of ciliated and parietal cells; the
      ciliated cells are arranged in seven rows and are associated by junctions with
      other cells in the same row as well as with those in adjacent rows. They are also
      associated by junctions with peripheral parietal cells. Junctions between
      adjacent ciliated cells in all cases exhibit tight junctions or zonulae
      occludentes. However, these cell borders also possess fasciae or zonulae
      adhaerentes if they are in the same row and the ciliary rootlets insert-into
      these junctions. If the cells are in adjacent rows they exhibit adhaerentes
      junctions only in species belonging to the orders Phlebobranchiata and
      Aplousobranchiata. In contrast, if the cells in adjacent rows belong to the order
      Stolidobranchiata. they never exhibit any adhaerentes junctions and the ciliary
      rootlets of the basal bodies from the cilia insert instead into the tight
      junctions and the non-junctional membrane below them. At the homologous
      junctional borders between adjacent parietal cells and also at heterologous
      junctional borders between parietal and ciliated cells, tight junctions alone
      occur, with no co-existing adhaerentes junctions along their lateral borders.
      Again, fibrils from ciliary rootlets insert into zonulae occludentes. This shows
      that tight junctions are capable both of forming permeability barriers, in that
      they can be seen to prevent the entry of exogenous tracers such as lanthanum, and
      of acting as adhesive devices.

PMID- 18620230
TI  - The need for a constraining layer in the formation of monodomain helicoids in a
      wide range of biological structures.
AB  - 1. To be mechanically effective, supporting structures which are helicoidal need
      to be monodomain, with planar or concentric layers. 2. To achieve this in
      cholesteric liquid crystalline chemical models, a constraining surface is
      required. 3. The prediction which logically follows from this is that natural
      helicoidal systems in plant cell walls, spores, animal eggshells and cuticles
      need to be secreted within an initial constraining layer. 4. Evidence in support
      of this prediction is presented for a wide range of living systems, by
      reinterpretation of published work. This helps, at least partly, to explain the
      profusion of different kinds of layers in skeletal structures. 5. By contrast,
      systems lacking constraining layers have polydomain texture. 6. In plants, normal
      turgor pressure appears to be required for the deposition of monodomain
      helicoidal wall layers: reduced pressure leads to polydomain helicoid.

PMID- 18620231
TI  - The fine structure of the dorsal ocelli in the male bibionid fly.
AB  - The dorsal ocelli of bibionid flies, details of which have not previously been
      described, were examined in males of Dilophus febrilis. The three ocelli are
      combined within an elevated chitin capsule, in a medial position between the
      enlarged dorsal compound eyes. The biconvex lenses show a multiple layering of up
      to 150 regularly spaced, clear and dense cuticle zones (100 nm spacing) which
      probably provide some spectral filtering, suggested by in vivo observations with
      an epifluorescence microscope. The corneagenous cells and the retina with 100-200
      photoreceptor cells are adjoined proximally. A distal retina zone comprises the
      rhabdoms, which are laterally connected in an hexagonal network. The rhabdoms are
      between 4 and 15 mum in length; they decrease gradually from the dorsal to the
      ventral retina region. A middle retina zone comprises the receptor somata, a
      proximal zone, their axons. Synaptic contacts between axons and interneuron
      dendrites, feedback synapses to axons, and axo-axonic synapses are found, showing
      varying pre-synaptic structures. A possible functional role of the ocelli is
      discussed.

PMID- 18620232
TI  - Revertants of mouse cells transformed by murine sarcoma virus. III. Metastable
      expression of virus functions in revertants retransformed by murine sarcoma
      virus.
AB  - 3T3FL cells transformed by the Moloney murine sarcoma virus (MSV) (sarcoma
      positive, leukemia negative, S+L- cells) segregate spontaneous flat revertants.
      These S-L- revertants do not release MSV upon superinfection with MuLV but are
      susceptible to a second cycle of single-hit MSV transformation. The behavior and
      nature of second-cycle MSV transformed revertants were followed by successive
      clonal generations. The second transformation by MSV resulted in a number of
      metastable states. The simplest of these was a tranformed S+L- like state, which
      in contrast to parental S+L- cells, was also inducible by halogenated
      pyrimidines. A second type consisted of a transformed S+L- clone which could give
      rise to a secondary flat S-L- clone, which when followed over several generations
      could turn again into a stable S+L- type cell. Thus an MSV genome can persist in
      a nontransformed cell in a nonrescuable state. A third condition has been found
      in which a previously S+L- type MSV retransformed revertant began to produce
      infectious MSV with or without an atypical murine leukemia virus (MuLV). Other
      clonal sublines from a second cycle MSV transformed cell resulted in both a
      stable S+L- type line and a spontaneous MSV releaser line. The S+L- type
      retransformed cell resembled parental single cycle MSV transformed S+L- cells in
      that it contained MuLV group specific antigen(s), and C type particles. Some
      second cycle MSV transformed S+L- cells produced infectious MSV on chemical
      induction. No second-cycle reversion was ever observed, if both the first and the
      second infecting genomes were Moloney-MSV. The nature of the atypical MuLV was
      examined in terms of host range, growth potential, and antigenicity. This MuLV
      was at times released with an apparent excess of MSV, yet if eleven weekly blind
      passages of such a virus stock were made in S+L- cells, replicating MuLV was
      found in titers similar to the MSV content. This atypical virus replicated in
      mouse cells, less in rat cells, but not at all in human or cat cells.
      Neutralization revealed that it was closely related to the Moloney type of MuLV.
      The above observations are compatible with the interpretation that the second
      cycle of MSV transformation destabilizes cellular controls over the transforming
      genome.

PMID- 18620233
TI  - Serial passage of strawberry crinkle virus in the aphid Chaetosiphon jacobi.
AB  - Strawberry crinkle virus was maintained through 6 consecutive serial passages by
      needle inoculation of the aphid vector, Chaetosiphon jacobi. A dilution factor of
      at least 10(-3) at each passage, coupled with a high rate of successful
      inoculation (ca. 90%) and a stable incubation period, indicated that the virus
      titer was being maintained by multiplication in the aphid.

PMID- 18620234
TI  - Ultrastructure of the photoreceptor of Diplolaimella sp. (Nematoda).
AB  - The photoreceptor of the free-living marine nematode Diplolaimella sp. is
      ultrastructurally described. The most prominent feature of the photoreceptor is
      called the 'ocellar complex' and is composed of three dorso-laterally located
      parts. (1) The lens is an amorphous half sphere-shaped structure, about 1.5 mum
      in diameter. (2) The receptoral part is a stack of slightly undulating lamellae,
      localized just posterior to the lens. (3) The receptoral part is surrounded by a
      pigment cup containing electron-dense granules of 0.1-0.3 microm diameter. These
      three parts are embedded in a cell process, which has a more sizeable ventral
      extension containing the nucleus and cytoplasm characterized by a lot of free
      ribosomes and broad cisternae of the granular endoplasmic reticulum. This sheath
      cell is supposed to synthesize the pigment. The above described structure occurs
      bilaterally paired, some 50 microm from the anterior end.

PMID- 18620235
TI  - Excretion in the house cricket (Acheta domesticus): ultrastructure of the ampulla
      and ureter.
AB  - An ultrastructural analysis of the ampulla and ureter of the cricket, Acheta
      domesticus, is presented. The excretory system of the cricket is unusual in that
      the 112 Malpighian tubules do not attach directly to the gut, but fuse to form a
      bladder-like ampulla which is joined to the colon by a muscular ureter. The
      ampulla consists of two cell types, primary and regenerative. Primary cells
      secrete large numbers of membrane-bound vesicles into the lumen and also appear
      to be involved in fluid reabsorption. Regenerative cells are very small and form
      a layer just beneath the basal lamina of the ampulla. They are believed to
      differentiate and replace sloughed off primary cells. The ureter is a muscular
      tube lined with cuticle which connects the ampulla (endoderm) with the colon
      (ectoderm). The probable origin and significance of the morphological
      modifications of the excretory system are discussed.

PMID- 18620236
TI  - Excretion in the house cricket (Acheta domesticus): fine structure of the
      Malpighian tubules.
AB  - An ultrastructural analysis of the Malpighian tubules of the cricket, Acheta
      domesticus, is presented. The excretory system of the cricket is unusual in that
      the 112 Malpighian tubules do not attach directly to the gut, but fuse to form a
      bladder-like ampulla which is joined to the colon by a muscular ureter. The
      tubules have three structurally distinct segments and consist of four cell types.
      Attached by basal lamina to the outer surface of the distal tip are nodules,
      consisting of small cells on membranous stalks. These are presumed to serve as
      attachments to the body wall. The distal 20% of the tubule is hyaline, consisting
      of a monolayer of squamous cells that appear to be secretory. The mid-tubule
      comprises 75% of the total length and is the primary region for fluid secretion.
      It is also characterized by having large numbers of laminate spheres in the
      cytoplasm of the cells. The proximal 5% of each tubule consists of more columnar
      cells and may function in fluid resorption. The relationship between structural
      features and known physiological functions are discussed.

PMID- 18620237
TI  - On the numbering of peripheral doublets in cilia and flagella.
AB  - The nine microtubular doublets of cilia and flagella have distinctive features
      that make it possible to assign an index number to each of them. Such an indexing
      has been used for a long time for animal cilia and flagella, whereas other
      indexing systems have been proposed recently for plant cilia. It is shown here
      that the similarity between cilia from animals and cilia from plants and protists
      is so great that the same indexing system can be used for all cilia regardless of
      their derivation.

PMID- 18620238
TI  - Immunolocalization of prophenoloxidase among hemocytes of the silkworm, Bombyx
      mori.
AB  - Silkworm (Bombyx mori) hemocytes were fixed immediately after collection. Thin
      sections of the hemocytes were stained by an indirect immunogold staining method
      using rabbit anti-prophenoloxidase/IgG as a primary antibody and colloidal gold
      coated with goat anti-rabbit/IgG as a secondary antibody. Electron micrographs of
      the sections revealed that only plasmatocytes and oenocytoids have
      prophenoloxidase both in cytoplasm and nucleus whereas granulocytes,
      spherulocytes and prohemocytes do not have appreciable amounts of the proenzyme.
      Cytoplasmic inclusions of oenocytoids also contain the proenzyme. A wide variety
      of concentrations of prophenoloxidase was observed among oenocytoids.
      Plasmatocytes appeared to have less prophenoloxidase than any oenocytoids. Once
      materials in the granules of granulocyte were discharged into the plasma and
      formed coagula, they cross-reacted with antiprophenoloxidase/IgG, suggesting that
      prophenoloxidase was trapped in the coagula by unknown mechanisms. This
      observation is discussed in relation to the dispute concerning the presence of
      prophenoloxidase or phenoloxidase in the granulocyte.

PMID- 18620239
TI  - Fine structural study of the acrosome formation in the starfish Marthasterias
      glacialis (Echinodermata, Asteroidea).
AB  - The fine structure of the spermatogenic cells in the starfish Marthasterias
      glacialis was studied regarding acrosome formation. The main finding in the
      spermatogenesis of M. glacialis is that the formation of the pro-acrosomal
      vesicles seems to be initiated in late spermatogonia. Small dense bodies
      resulting from the division of large granulofibrillar masses were also observed
      in the cytoplasm of late spermatogonia. During spermiogenesis the inner acrosomal
      vesicle membrane becomes coated first with dense materials originated from the
      cytoplasmic dense bodies and then with cisternae of endoplasmic reticulum. Both
      coating materials are incorporated in the periacrosomal space of the mature
      acrosome. Besides being involved in the genesis of the periacrosomal material,
      cytoplasmic dense bodies were also seen in close relationship with intercellular
      bridges and midpiece structures of spermatids. These findings are discussed in
      comparison with other echinoderm spermatogenesis.

PMID- 18620240
TI  - Arthropod immune system. III. Septate junctions in the hemocytic capsule of the
      german cockroach, Blattella germanica.
AB  - Granulocytes (GRs) and/or plasmatocytes (PLs), the two major immunocytes in
      arthropods, participate in cellular encapsulation of foreign tissue. Although gap
      and desmosome junctions have been reported in insect capsules, smooth septate
      junctions are being reported for the first time by both thin section and freeze
      fracture techniques in Blattella germanica. In 7-day-old capsules, the septa are
      23 nm thick, faintly 'scalloped' and slightly curved in appearance; the
      interseptal space has a periodicity of about 5 nm. In freeze-fractured capsules,
      the septa are associated on both sides with the corresponding intramembranous
      structures, belonging to the plasma membranes of the two junction-forming GRs.
      The intercellular space is 27 nm wide. There are 36-40 septa/1 microm junctional
      length. The junctions show furrows on the extracellular fracture face (E) and the
      complementary regular rows of intramembranous particles on the cytoplasmic face
      (P). The septate junctions often occur in the region of the capsule that also
      shows the presence of gap junctions, but only rarely that of desmosomes. The
      septate junctions are in close proximity with mitochondria. It is suggested that
      the function of these junctions is to produce compact capsules.

PMID- 18620241
TI  - Luminescent activity and ultrastructural characterization of photocytes
      dissociated from the coelenterate Renilla kollikeri.
AB  - Dissociation and Percoll sedimentation techniques were used to separate and pool
      the autofluorescent luminescent cells (photocytes) of the pennatulid anthozoan
      Renilla kollikeri. Photometric recordings of luminescent activity of photocyte
      suspensions show that activation of flashing and glowing by KCl depolarization is
      suppressed in calcium-free sea water and by cobalt but enhanced by
      trifluoperazine, thus suggesting that luminescence excitation is dependent on
      extracellular calcium and calmodulin-mediated mechanisms. Of several neuroactive
      substances tested, adrenaline, dopamine, N-methyl-N-phenylethanolamine, serotonin
      and the native neuropeptide Antho-RFamide all induced photocyte responses at high
      concentrations (0.1-1 mM) only, whereas lower concentrations of adrenaline and
      Antho-RFamide are known to activate or enhance luminescence or muscular
      contractions in intact Renilla tissues (Anctil et al., 1982; Anctil, 1987).
      Hence, none of these substances is a likely neurotransmitter candidate for direct
      photocyte activation. Ultrastructural observations of dissociated photocytes
      reveal that they are musculo-epithelial cells containing numerous 0.2-mum
      vesicles resembling previously extracted and light-emitting lumisomes (Anderson
      and Cormier, 1973). Similar cells were traced ultrastructurally in situ in the
      endodermal luminescent zones, but not in non-luminescent endoderm.

PMID- 18620242
TI  - The tardigrade cuticle. I. Fine structure and the distribution of lipids.
AB  - Fine structure and lipid distribution are studied in cuticles of five tardigrade
      species using TEM and SEM. Double osmication using partitioning methods reveals a
      substantial lipid component in the intracuticle and in irregular granular regions
      within the procuticle. These results are substantiated by the loss of osmiophily
      following lipid extraction with chloroform and methanol. Other lipid components
      are revealed by osmication following unmasking of lipo-protein complexes with
      thymol. These occur in the outer epicuticle and in the trilaminar layer lying
      between the epi- and intracuticles. Anhydrous fixation of dehydrated tardigrades
      (tuns) reveals dense, superficial masses of osmiophilic material, apparently
      concentrated lumps of the surface mucopolysaccharide ('flocculent coat').
      However, cryo-SEMs of tuns reveal similar dense aggregations which apparently
      exude from pores (not visible) and are removed by chloroform. These results
      suggest extruded lipids since the flocculent coat is unaffected by chloroform;
      likely functions of such lipids are discussed.

PMID- 18620243
TI  - Size of secretory granules from midgut cells of the stablefly, Stomoxys
      calcitrans.
AB  - The size frequency distribution and number of secretory granules in the opaque
      zone midgut cells of the stablefly Stomoxys calcitrans have been determined using
      several independent methods. Average mean secretory granule diameter is 0.45
      microm. Mean number of secretory granules per cell is 28,560. The diameter of the
      granules is compared to the size of secretory granules found in complementary
      vertebrate tissues and the consequences for the cell of the differences in the
      size of the granules is discussed.

PMID- 18620244
TI  - Glial cells in peripheral nerves of the cockroach, Periplaneta americana.
AB  - The ultrastructural organization and the junctional complexes of peripheral
      nerves have been investigated in the cockroach Periplaneta americana. Nerve 5 is
      surrounded by a layer of connective tissue, the neural lamella, beneath which is
      a layer of perineurial glial cells wrapping the axons. Adjacent perineurial cells
      are joined to one another by septate, gap and tight junctions. Septate and gap
      junctions were observed in freeze-fracture replicas of main trunk nerve 5.
      Septate junctions were found as rows of PF particles mainly in perineurial cell
      membranes. Gap junctions exhibited EF macular aggregates in perineurial and
      subperineurial glial cells. During incubations in vivo with extracellularly
      applied ionic lanthanum, the lanthanum did not penetrate beyond the perineurium.
      Where nerve 5 branches and contacts the muscle, lanthanum penetrated freely
      between the muscle fibres and the nerve branches. In small peripheral branches
      where the axons are surrounded by single a glial layer, lanthanum is unable to
      penetrate to the axolemma.

PMID- 18620245
TI  - The flea ovary: ultrastructure and analysis of cell clusters.
AB  - Panoistic ovarioles are found in the order of fleas (Siphonaptera). Only in some
      species of the Hystrichopsylloidea do polytrophic meroistic ovaries occur. No
      stem cells and no dividing cystocytes are found in female imagines of
      Hystrichopsylla talpae. However, each germ cell cluster consists of 32 cells
      which are generated by five mitotic cycles during the pupal stage. One of the
      cells containing five intercellular bridges becomes the oocyte, the others serve
      as nurse cells. Thus, germ cell cluster formation follows the 2(n)-rule. However,
      no polyfusome is found and nurse cells do not form a rosette. Furthermore, nurse
      cells remain small and show the same ultrastructural characters as the oocytes,
      which became distinguishable from nurse cells only by their enhanced growth
      during pre-vitellogenesis. The first phase of pre-vitellogenesis is dominated by
      the production of an unknown cytoplasmatic component, consisting of spherical
      particles, clearly distinguishable from ribosomes by diameter and contrast. The
      next phase is characterized by a tremendous increase in the production of
      ribosomes. During this second phase another cytoplasmic component consisting of
      ball-like structures becomes prominent. During pre-vitellogenesis, germ cell
      nuclei undergo a pronounced structural change in which, finally, numerous
      extranucleolar particles predominate. Thus, H. talpae has a polytrophic meroistic
      ovary, but its oocyte genomes behave panoistically.

PMID- 18620246
TI  - Ultrastructural and cytochemical studies in the mantle of Anodonta cygnea.
AB  - The large central region of the mantle of Anodonta cygnea was studied using
      transmission and scanning electron microscopy (TEM and SEM) for ultrastructural
      analysis and light microscopy (LM) and TEM for cytochemical analysis. X-ray
      diffraction studies of the organic matrix pellicle deposited on the inner surface
      of the shell were also carried out. Two groups of columnar cells presenting
      desmosomes on the apical region were observed in the outer epithelium. One group
      secretes a structural and neutral mucopolysaccharide (MPS) identified with
      chitin, normally excreted to form the organic matrix of the shell. Another group
      presents numerous cytoplasmic vesicles and constitutes the predominant cells of
      this epithelium. Two different types of mucous cells were found in the inner
      epithelium. One type secretes a faintly acid mucopolysaccharide (MPS) with
      sulphate groups and another type secretes an association of this polysaccharide
      with a neutral MPS. Staining for sulfhydryl groups (probably cysteine) was also
      positive, suggesting the presence of proteoglycans in these secretions. A third
      type of cells was also observed presenting a very different ultrastructural
      aspect (columnar form) without large secretion masses. They may correspond to the
      replacing cells in this highly secretory epithelium. Elastic fibers were found on
      the base of the outer epithelium and amoebocytes were observed in the
      interepithelial tissue.

PMID- 18620247
TI  - Electron microscopy of the germ cells and the ovarian wall in Xiphinema
      (Nematoda).
AB  - The ovary of Xiphinema theresiae is studied ultrastructurally. It consists of two
      cell types, the ovarian epithelial cells and the germ cells. The ovarian
      epithelial cells form a thin layer around the germ cells. Their nuclei are
      located in between the germ cells. At some sites, processes of the ovarian
      epithelial cells migrate inward and form a central cytoplasmic mass. The germ
      cells have a large lobated nucleus, with an eccentric nucleolus, and are
      considered to represent young previtellogenic oocytes. In contact with the
      central cytoplasmic mass, the germ cells develop two membrane derived features,
      the villi and the small coated bulges, which most probably play a role in
      transport.

PMID- 18620248
TI  - The source of lipids and polyphenols for the insect cuticle: The role of fat
      body, oenocytes and oenocytoids.
AB  - The newly fed fourth instar larva of Rhodnius lays down the outer epicuticle at 8
      9 days, the inner epicuticle at 9 days, and it moults at 12 days. The oenocytes,
      which supply the lipid precursors, reach their maximum size at 7 days when lipid
      spheres and lipid-coated vesicles appear in their cytoplasm. The epidermal cells
      extend cytoplasmic strands to the contracting oenocytes and receive abundant
      lipid, which they transfer to the plasma membrane for construction of the outer
      and inner epicuticle. The oenocytes also transfer lipid to the epidermis attached
      to the basal lamina. This lipid is discharged through the lamina and taken up by
      ocnocytoids. which apply themselves to the basal lamina and liberate this copious
      absorbed material into the haemolymph before disintegrating. The synthesis of
      polyphenols for sclerotization takes place in the fat body, reaching a peak at
      day 10. After discharge into the haemolymph it is taken (presumably by a carrier
      protein) to the epidermis, where its uptake and transfer can be monitored by
      argentaffin staining. The tubular system of pore canals and tubular filaments is
      formed by invagination of the plasma membrane immediately after the inner
      epicuticle is complete, and is filled with lipid precursors and polyphenols.
      There is evidence that these metabolites are carried separately: the lipid in
      multiple tubular filaments; the polyphenol through the substance of the axial
      filament. Lipid and polyphenols are still supplied to the epidermis during days
      10-12. Both are most richly supplied to the sites forming exocuticle-which
      illustrates the importance of lipid as well as polyphenol in cuticle hardening.

PMID- 18620249
TI  - Cytometric investigations on hemocytes of the American oyster, Crassostrea
      virginica.
AB  - Pericardial hemolymph was obtained from American Oysters (Crassostrea virginica)
      and the hemocytes characterized by flow cytometry. The cells were found to have a
      broad unimodal size distribution with a median diameter of 7 micrometers. Total
      protein measured by flow cytometric fluorescence of dansylated cells also
      revealed a broad unimodal distribution similar to that obtained for size. The
      proportion of hemocytes in each stage of the cell cycle was measured using DNA
      specific DAPI fluorescence. Histograms showed a single peak representing the
      G(0)/G(1) population. There was no evidence of S or G(2)+M phases of the cell
      cycle, nor was polyploidy seen. The forward and orthogonal light scatter of fixed
      hemocytes showed no evidence of sub-populations on the basis of cytoplasmic
      granularity. Thus, in terms of these parameters, oyster hemocytes appear to
      represent a single population exhibiting graded cellular differences.

PMID- 18620250
TI  - Hatching envelope formation in shrimp (Sicyonia ingentis) ova: Origin and
      sequential exocytosis of cortical vesicles.
AB  - The ova of Sicyonia ingentis lack cortical vesicles at the time of spawning.
      Within 30 min post-spawning, two populations of cortical vesicles are organized
      in the ooplasm which, during cortical vesicle exocytosis (cortical reaction),
      successively release two morphologically different exudates. The first type of
      cortical vesicles (dense vesicles) appears to be derived from the Golgi complexes
      after spawning. The second type (the ring vesicles) is formed by the fusion of
      asternal elements which contain loosely packed ring-shaped structures that are
      present in the unactivated ova. During exocytosis of the dense vesicles an
      electron dense material is released which coalesces with the surface coat of the
      ovum to form a thin hatching envelope which eventually lifts from the ovum's
      surface. Subsequent to the formation of the thin hatching envelope, the ring
      vesicles undergo exocytosis resulting in an accumulation of ring-shaped
      structures in the perivitelline space. These structures coalesce and form an
      electron translucent layer on the inner surface of the thin elevated envelope to
      form the thickened hatching envelope. The formation of the cortical vesicles,
      their exocytosis and the elaboration of the hatching envelope are normally
      completed within 40-45 min after spawning.

PMID- 18620251
TI  - Cnidocytes and adjacent supporting cells form receptor-effector complexes in
      anemone tentacles.
AB  - Cnidocytes, the stinging cells of enidarians, discharge enidae (intracellular
      capsules containing eversible tubules) in response to physical contact combined
      with the stimulation of specific chemoreceptors. These receptors, occurring in at
      least two classes, bind N-acetylated sugars and certain amino-compounds,
      respectively (Thorington and Hessinger, 1988). Colloidal gold coated with bovine
      submaxillary mucin (mucin-gold) binds exclusively at the surface of the
      supporting cells which surround enidocytes (Watson and Hessinger, 1986). We now
      find that mucin-gold sensitizes enidocytes to discharge nematocysts in a dose
      dependent manner. In addition, we find that the number of mucin-gold particles
      appearing at the surface of supporting cells changes over time, and that such
      changes correlate with the time-course of enidocyte responsiveness. Thus, the
      discharge of nematocysts by enidocytes may be regulated by the number of receptor
      ligand complexes at the surface of the adjacent supporting cells. We conclude
      that enidocytes and supporting cells constitute receptor-effector complexes.
      Subsequent to binding at the cell surface, mucin-gold is endocytosed (Watson and
      Hessinger, 1987a). Multivesicular bodies seem to dispose of the endocytosed mucin
      gold at the cell surface rather than via lysosomes. This novel route appears to
      be the major pathway by which endocytosed mucingold is removed from supporting
      cells.

PMID- 18620253
TI  - Actin localization at the tight junctions of invertebrate ciliated epithelia.
AB  - Indirect immunofluorescencc, rhodamine-phalloidin staining and immunoelectron
      microscopy performed with the on-grid postembedding immunostaining of Lowicryl
      K4M sections, were used to identify actin in the branchial epithelium of the
      lower chordate ascidians. The ciliated cells of these invertebrates present two
      distinct junctional patterns. One consists only of an extended tight junction
      whereas in the other the tight junction is accompanied by a prominent zonula
      adhaerens. Evidence is given of the localization of actin at the tight junction.
      The absence of reaction in the zonula adhaerens suggests that the definition of
      this junction in the model here presented must be reconsidered.

PMID- 18620252
TI  - Directed migration of cells from the sponge Geodia cydonium.
AB  - The migration behavior of cells from the sponge Geodia cydonium was studied in
      vitro, applying the 'Tissue Culture Slide Chamber' technique. The homologous
      lectin caused a directed cell migration with a maximal locomotory rate of 1.6
      mum/min. Competition experiments using the solubilized lectin receptor (=
      antiaggregation receptor) revealed that the chemotactic ligand (= lectin)
      interacts directly with the lectin receptor which-in consequence-functions as the
      chemotactic receptor. The ability of the lectin to promote cell migration is
      abolished by coincubation with purified leucine aminopeptidase. Biochemical and
      immunochemical data revealed that this enzyme is present also on the surface of
      sponge cells. Furthermore, we present evidence that the chemotactic receptor (=
      anti-aggregation receptor) on the cell surface is, in an hitherto unknown manner,
      coupled with the intracellularly present actin filaments. From these data we
      conclude that the directed migration of Geodia cells is mediated by the
      interaction between the lectin (= chemotactic ligand) and the lectin receptor (=
      chemotactic receptor); it is very likely that also intracellular structural
      elements operate simultaneously and coordinately during cell migration.

PMID- 18620254
TI  - Fine structure of shark leucocytes during chemotactic migration.
AB  - It has previously been demonstrated that peripheral blood leucocytes of the nurse
      shark (Ginglymostoma cirrhatum) are capable of in vitro chemotaxis. In the
      present study we have identified the chemotactic cells as the shark granulocyte
      and monocyte-macrophage. Chemotaxis assays were set up in blind well chambers.
      Cells migrating into the filter in a chemotaxis assay were identified
      morphologically by transmission electron microscopy. Migration, in response to
      LPS-activated rat serum, was accompanied by change in cell shape and
      reorganization of the cytoskeleton. Ultrastructural changes included formation of
      lamellipodia with cell polarization, submembranous accumulation of microfilaments
      at points of plasma membrane contact with filter surfaces, densification of the
      membrane at these points of engagement, appearance of bundles of intermediate
      filaments extending into the protruded lamellipodia, and presence of oriented
      microtubules in the cytoplasma (cellular cortex). The phagocytic and chemotactic
      properties of the shark granulocyte and monocyte-macrophage points to their being
      structural and functional equivalents of the mammalian neutrophil and macrophage.

PMID- 18620255
TI  - Spiracular closing mechanisms in the firebrat, Thermobia domestica (packard)
      (Thysanura).
AB  - Mechanisms for regulating the degree of opening of its spiracles are present in
      Thermobia. That of the mesothoracic spiracle is of the external type with a flap
      like hood guarding the spiracular aperture. Contraction of muscles open the
      spiracle by raising the hood. Closure is brought about by muscular relaxation and
      elastic cuticular recoil. Opening is either partial, with small-scale oscillatory
      movements ('fluttering'), or complete ('wide-opening'). Wide-opening follows
      bouts of muscular activity. Carbon dioxide anaesthesia relaxes the opener muscles
      causing the spiracles to close by elastic recoil. This explains continued low
      tracheal water loss during anaesthesia, and also in death. The control mechanisms
      of the metathoracic and 8 pairs of abdominal spiracles are of the internal type,
      with a crypt-like atrium leading into the slit-like neck region of the spiracular
      pit, one side of which has an elastic cuticular rod running along it. Muscles
      inserted on the opposite side widen the aperture. As with the mesothoracic
      spiracle, closure is brought about by muscular relaxation and elastic cuticular
      recoil.

PMID- 18620256
TI  - Fine structure of the pheromone-sensitive sensilla on the antenna of the
      hawkmoth, Manduca sexta.
AB  - The flagellar antenna of the male hawkmoth Manduca sexta carries about 42,000
      pheromone-sensitive sensilla trichodea, which are arranged in 'baskets' on the
      single segments. Each sensillum consists of a cuticular hair up to 500 mum long
      and is innervated by two bipolar sensory neurons. Each neuron sends an unbranched
      dendrite into the hair shaft. The dendrite is subdivided by a short ciliary
      region into an inner and an outer segment. The inner segment is especially rich
      in smooth vesicles, which accumulate beneath the ciliary region where they seem
      to fuse with the dendritic membrane. The outer dendritic segment often shows
      conspicuous 'beads' along its length. Three auxiliary, or enveloping, cells
      belong to each adult sensillum. These are the thecogen, the trichogen, and the
      'outer' cell. Most probably, the latter is not homologous with the 'traditional'
      tormogen cell from a genealogical point of view.

PMID- 18620257
TI  - Membranous tubes in pseudoscorpion spermiogenesis.
AB  - The highly complicated differentiation of the spermatid in the pseudoscorpion
      Diplotemnus sp. is accomplished without the presence of microtubules. Instead
      membranous tubes measuring approximately 50 nm in diameter and closely associated
      with endoplasmic reticulum are found from early to mid spermatids. The lumen of
      the tube is devoid of electron dense contents but a fluffy material is attached
      to the cytoplasmic side. They run straight or slightly bent and are in open
      connection with the cell membrane. First appearing near the cell bridge of the
      interconnected spermatids they form a bundle in the longitudinal axis during a
      transitory phase of elongation. When the cell rounds off again the tubules
      together with the endoplasmic reticulum disappear. The arrangement of the tubes
      and their presence during abortive elongation of the spermatid suggest a
      supportive function commonly attributed to microtubules. Moreover, the open
      connection with the cell membrane and their close association with the
      endoplasmic reticulum may indicate their participation also in transport.

PMID- 18620258
TI  - A single layer of microtubules is part of a complex cytoskeleton in mature
      nematocytes of hydra.
AB  - The architecture of microtubules in mature nematocytes (stinging cells) of Hydra
      attenuata was investigated in detail by an indirect immunofluorescence study and
      by scanning and transmission electron microscopy in order to comprehend the
      function of the cytoskeleton in this extremely complex cell type. Microtubules
      were detected in all types of nematocytes in the tentacles and were found to be
      arranged in parallel arrays forming a highly organized basket-like structure
      around the nematocysts.

PMID- 18620259
TI  - Ultrastructure of feeding in the karyorelictean ciliate Tracheloraphis examined
      by scanning electron microscopy.
AB  - The karyorelictean ciliate Tracheloraphis is considered to be among the most
      primitive of the extant ciliates based on both nuclear and somatic characters.
      These organisms lack the elaborate oral ciliation present in most ciliates. Their
      mode of ingestion is a type of phagocytosis through a non-ciliated region, the
      glabrous stripe, which runs the length of the cell. This type of ingestion is
      reminiscent of feeding in amoebae and some flagellate groups. It is possible that
      ciliate oral structures evolved within the karyorelictean ciliates from an
      ancestor resembling Tracheloraphis. We studied the ingestion process in a
      Tracheloraphis species from the Chesapeake Bay using scanning electron
      microscopy. The results indicate that the anterior terminus of the organism is
      not involved in the actual ingestion process, only the glabrous stripe. There is
      some interaction between the food particle and the surface of the stripe,
      possibly mediated by a substance secreted by the underlying extrusomes. The
      somatic cilia do not appear to be involved. The stripe invaginates at the
      ingestion site engulfing the particle. The cell becomes greatly distended at this
      site, but neither the anterior nor posterior terminus is affected.

PMID- 18620260
TI  - Intercellular junctions and rhombic particle arrays in the developing and adult
      dorsal ocelli of the honeybee.
AB  - Intercellular junctions and particle arrays in the developing and mature dorsal
      ocelli of the honeybee Apis mellifera have been studied with conventional and
      freeze-fracture electron microscopy. Four types of junctions are found in the
      lentigenic and retinogenic part during development. These are desmosomes, septate
      junctions, tight junctions, and gap junctions. Gap junctions and septate
      junctions are found between differentiating photoreceptor cells only as long as
      the rhabdoms are beginning to form. Their disappearance after differentiation
      indicates that they could play a part in cell determination. Desmosomes connect
      photoreceptor cells into the early imaginai stage and then disappear. Other
      junctions, once they have formed, remain for the life of the animal, but can
      change considerably in structure, distribution and frequency. The cells of the
      perineurium surrounding the ocellus are connected by septate and gap junctions,
      which may be the basis of the blood-eye barrier. Rhombic particle arrays on the E
      face of the glial membrane attached to the photoreceptor cell membrane first
      appear in small groups one day before emergence. In the further course of life
      these arrays become more extensive and apparent. Their significance may be to
      play some role in receptor function.

PMID- 18620261
TI  - Investigations on the midgut caeca of mosquito larvae-I. Fine structure.
AB  - Four types of cells can be distinguished in the epithelium of the caeca of three
      species of mosquito larvae. Specialized cells secreting a 160nm caecal membrane
      occur either near the opening of the caeca into the midgut (Aedes, Anopheles) or
      in the posterior half of the caeca (Culex). The presence of chitin could be
      demonstrated in this membrane with wheat germ agglutinin. In larvae of A. aegypti
      and C. pipiens the posterior part of the caeca is occupied by ion transporting
      cells. In larvae of A. stephensi these cells are interspersed among other cells,
      even in the anterior part of the caeca. The ion transporting cells resemble other
      insect cells involved in osmoregulation. Their microvillar membranes are studded
      with 14 nm portasomes and are closely associated with mitochondria. The main type
      of caecal cell seems to be responsible for resorption and storage of nutrients
      and for the secretion of enzymes. Small and undifferentiated cells were observed
      sporadically and seem to be imaginal cells.

PMID- 18620262
TI  - Investigations on the midgut caeca of mosquito larvae-II. Functional aspects.
AB  - Fluorescent dyes were used to observe antiperistaltic movements of the midgut
      which cause an anteriorly directed flow which provides the caeca with midgut
      fluid. Aminopeptidases could be demonstrated histochemically in the cells and
      lumen of the caeca. This would suggest that the caeca of mosquito larvae take
      part in the final degradation, resorption and storage of nutrients. The caecal
      membrane acts as a permeability barrier. Particulate material and substances
      which cannot be degraded or resorbed accumulate in the caeca. Moreover, the caeca
      are involved in osmoregulation. Changes in the number of mitochondria present in
      the microvilli of ion transporting cells occur. The number of mitochondria in the
      microvilli depends on the salinity of the culture medium of these larvae.

PMID- 18620263
TI  - The tardigrade cuticle II. Evidence for a dehydration-dependent permeability
      barrier in the intracuticle.
AB  - Tardigrades weighed during desiccation in high or low humidities show a short
      period of rapid transpiration followed by an abrupt decline in transpiration
      which virtually arrests water loss. The amount of water retained following this
      'permeability slump' is greater at low rates of desiccation but the slump is not
      a metabolic phenomenon, being reproducible in dead or narcotised animals.
      Tardigrades rinsed in hot chloroform (62 degrees C) for 5 hr still show the
      characteristic permeability decline when desiccated in 80% RH. However, 25hr
      rinsing in hot chloroform apparently obliterates the slump. Estimates of the
      bound water content of tardigrades by DSC show that this can account for the
      dehydrated masses of these chloroform-rinsed animals and that all free water is
      probably transpired. Lipid analysis of the 25 hr chloroform extracts by GC-MS
      reveals several lipid classes, predominantly free fatty acids (C(12)-C(18));
      these are not detectable in the 5 hr extracts. Control rinsing in hot water has
      no apparent effect on the permeability slump. TEM tracer studies with lanthanum
      show the lipid-rich intracuticle to serve as a transpiration barrier in
      dehydrated animals but not in fully hydrated specimens. There is thus strong
      support for the role of intracuticular lipids in effecting the permeability
      slump. A model to explain this phenomenon on the basis of lipid phase changes is
      postulated.

PMID- 18620264
TI  - The cercal sensilla of the blowfly Lucilia cuprina. II. Structure of the
      enveloping cells and the basal regions of the sensory dendrites.
AB  - The gustatory, olfactory, touch and stress receptors on the cerci of Lucilia
      cuprina Wied. (Diptera: Calliphoridae) have either two or three enveloping cells.
      The gustatory and olfactory sensilla have three enveloping cells: a tormogen,
      trichogen and thecogen cell. The tormogen and trichogen cells contribute to a sub
      cuticular sensillar lumen which divides into two lobes basally. The thecogen cell
      forms a lumen around the dendrites. Distally the dendrites lie in the contents of
      the thecogen lumen within the dendritic sheath. Proximally the dendrites embed in
      the thecogen cell which has an expanded, microlamellate lumen basally. The
      sensillar lumen of the mechanosensory (trichoid mechanoreceptors and campaniform)
      sensilla is formed by a single enveloping cell: the presumptive tormogen cell. In
      trichoid mechanoreceptors the thecogen lumen is restricted to the region of the
      transitional region of the dendrite whereas the thecogen lumen of campaniform
      sensilla extends proximally although it is not as well-developed as that of the
      chemoreceptive sensilla. The dendrites of all sensillum types on the cerci have a
      granular body in the transitional region: a situation which has not been
      previously reported in chemoreceptive sensilla although common in the
      mechanoreceptors of Calliphoridae and Sarcophagidae.

PMID- 18620265
TI  - Ultrastructural changes in the gill epithelium of the green crab Carcinus maenas
      in relation to the external salinity.
AB  - Observation of semi-thin and ultrathin sections performed in the gills of green
      crabs (Carcinus maenas) kept in 100% and in dilute 30% sea water respectively
      reveals marked differences between the six anterior and the three posterior pairs
      of gills. The anterior gill lamellae are almost entirely lined by a thin pavement
      epithelium (0.9 to 3 mum thick) which does not undergo any noticeable change when
      crabs are acclimated from full to dilute sea water. This supports the view it is
      chiefly involved in the respiratory function. In addition to the pavement
      epithelium, the posterior gills exhibit small areas corresponding to a thick
      prismatic epithelium (10 mum) the ultrastructure of which is similar to that of
      most of the so-called 'salt transporting epithelia'. When submitted to reduced
      external salinity, this epithelium undergoes structural changes consisting of
      elaboration of an extensive apical plasma membrane infolding system, enlargement
      of the subcuticular compartment and close association of mitochondria with
      basolateral membrane infoldings. Pilaster cells exhibit ultrastructural features
      of either thin (respiratory) or thick (salt transporting) epithelial
      differentiation according to their localization within the gill. Their peculiar
      organization suggests they ensure, in addition, mechanical reinforcement of the
      gill lamellae against blood hydrostatic pressure. The fact that salt-transporting
      epithelium areas do not exceed, at most, 30% of the total lamellar surface is
      probably related to the weak osmoregulatory capabilities of the shore crab.

PMID- 18620266
TI  - Oogenesis in Hydra carnea: A new model based on light and electron microscopic
      analyses of oocyte and nurse cell differentiation.
AB  - Oogenesis in Hydra carnea starts with an accumulation of a great number of I
      cells in the interstitial spaces of the ectoderm of the body column. One
      centrally located I-cell becomes the future oocyte, the others differentiate into
      nurse cells. Presumptive oocyte and nurse cells are not easily distinguishable at
      that time. The earliest stage of an oocyte we could identify on ultrastructural
      criteria was in prophase of its first meiotic division. Only at this stage
      autosynthesis of nutritive substances predominates, the following rapid increase
      of the oocyte volume relies on the successive adoption of cytoplasmic fragments
      from nurse cells. Extending fingerlike processes between the epitheliomuscular
      cells, the oocyte then starts to phagocytose apoptotic nurse cells. Nurse cell
      differentiation is indicated by the appearance of lipid vesicles in I-cells. As
      differentiation proceeds glycogen, rEr and Golgi complexes appear and the cells
      increase due to a continuous production and accumulation of lipid, glycogen and
      yolk-like electron dense material. Then the loss of cytoplasmic fragments and
      degenerative changes typical of apoptosis, a morphologically defined form of cell
      death, converts the nurse cells into apoptotic bodies. The bulk of nurse cells
      becomes phagocytosed by the oocyte at late stages of their transformation into
      apoptotic bodies. At the end of oogenesis which in Hydra carnea takes about 4
      days, the egg consists for the largest part of apoptotic nurse cells which
      persist in the developing embryo until hatching.

PMID- 18620267
TI  - The phorbol ester TPA dramatically inhibits planarian regeneration.
AB  - The effect of phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) on head
      regeneration in decapitated planarians (Dugesia lugubris s.1.) has been studied.
      TPA-treatment soon after head amputation dramatically inhibited the regenerative
      process. Ultrastructural analysis revealed that the migration of fixed
      parenchymal cells (FPCs) to the wound area was strongly activated by TPA. FPCs
      interacted with various types of cells inducing lysis and phagocyting cell
      debris. The resulting fluid was removed through diaphanous protrusions appearing
      at the level of the wound zone. Moreover the close association of FPCs with
      neoblastlike cell clusters in the parenchyma indicated their possible role in the
      modulation of neoblast migration.

PMID- 18620268
TI  - Ultrastructure of the embryonic dorsal organ of Orchestia cavimana (crustacea,
      amphipoda); with a note on localization of chloride and on the change in calcium
      deposition before the embryonic moult.
AB  - The transitory dorsal organ of Orchestia cavimana appears simultaneously with the
      development of the germ layer and is gradually reduced during the last 2-3 days
      of embryonic development. It represents the only direct connection of the embryo
      with the chorion or-after the embryonic moult-with the embryonic envelope. The
      shape is hemispherical and it consists of about 50 bottle-shaped cells, arranged
      radially around a centre. This centre is filled with different kinds of
      extracellular material which forms a central plug apically and a central cone
      below it. The bottle-shaped cells taper apically. The neck region of these cells
      is characterized by numerous microvilli which project into the intercellular
      space. This space is filled with an electron dense substance and is in contact
      with the central cone. In the basal neck region numerous mitochondria are
      associated with the microvilli. The high density of mitochondria is
      characteristic for the nuclear region. The cytoplasm of the basal region below
      the nucleus contains numerous calcium granules. Evidence for the concentration of
      chloride in the apical dorsal organ is shown. Before the embryonic moult and
      during the duplication of the egg-volume the number of calcium granules in the
      dorsal organ and the integument is reduced. Simultaneously calcium granules
      appear in the now visible periembryonic space. This suggests that part of the
      calcium is shifted into this space. The function of the dorsal organ is
      discussed. Besides the probable main function-transport activity of ions-its role
      before and during embryonic moult and its part in the utilisation of yolk are
      discussed.

PMID- 18620269
TI  - Deposition of calcium salts in oocytes and ovarian somatic tissue of millipedes.
AB  - Until recently calcium concretions commonly encountered in the millipede ooplasm
      were considered as mineral store, incorporated in larva exoskeleton during
      embryogenesis. The presence of mineral bodies also in somatic tissues of
      millipedes (including ovarian epithelia) suggests that their appearance is mainly
      associated with detoxification of physiologically active mineral ions excess.

PMID- 18620270
TI  - The same cell lineage is involved in scale formation and regeneration in the
      teleost fish Hemichromis bimaculatus.
AB  - The elasmoid scales of the cichlid fish, Hemichromis bimaculatus, are localized
      within dermal pockets, the floors of which are separated from the stratum
      compactum by uninterrupted cellular sheets, the scale-pocket linings (SPL). TEM
      study of the fry skin shows that the SPL cells originate from the cell population
      constituting the dermal papilla of the scale. The upper-layer cells of the
      papilla, close to the epidermal-dermal junction, differentiate into scleroblasts
      that, subsequently, form the scale-bag, while the inner-layer cells, close to the
      stratum compactum, constitute a bi-layered sheet, the SPL. The SPL cells are
      joined one to another by numerous desmosomes and their cytoplasm is filled
      principally by microfilaments and free ribosomes. The SPL is also characterized
      by the presence of a basement membrane on its two faces. When a scale is
      experimentally pulled off, the scale-forming cells are removed with the dermis
      and the epidermis covering the free region of the scale, but the SPL is not
      damaged and epidermal fragments remain at the posterior edge of each scale
      pocket. The epithelial cells migrate, from the epidermal fragments, on an
      extracellular matrix situated on the surface of the SPL, and the wound is closed
      from 3 to 6 h after scale removal. The scale-regenerating cells differentiate
      from the upper-layer cells of the SPL, initially in the central region of the
      scale-pocket where epithelial cells first contacted the SPL surface.
      Consequently, it is shown that scale-forming cells and scale-regenerating cells
      are derived from the same ontogenetic population, the dermal papilla.

PMID- 18620271
TI  - The formation of plasma membrane reticular systems in the oenocytes of an insect.
AB  - Plasma membrane reticular systems (RSs) are infolds of the plasma membrane found
      in cells of several insect tissues that are not transporting epithelia. They form
      a subsurface reticular lymph space that may be involved in the loading and
      unloading of hemolymph carrier molecules. The development of a new RS during the
      fifth larval stadium has been studied in the oenocytes of Calpodes ethlius by
      scanning electron microscopy. The RS forms by the extension and progressive
      apical fusion of cell processes leaving a reticular lymph space below. Reticular
      system formation occurs in a front moving over the cell surface. The RS made in
      the 4th stadium persists through the moult to the 5th stage but diminishes for
      the next 3 days. A new intermoult RS then forms very quickly. Its time of
      formation follows the commitment ecdysteroid peak rather than the beginning of
      secretion by the wax glands. This new 5th stage RS is maintained during the
      period of intermoult synthesis, after which it declines and is nearly absent by
      the time of pupation.

PMID- 18620272
TI  - Electron microscopic and microprobe analysis of calciuminduced differentiation of
      the white mutant (LU887 x LU897) strain of Physarum polycephalum.
AB  - Differentiation of the white mutant (LU887 x LU897) strain of Physarum
      polycephalum leading to spherule formation can be induced by CaCl(2) if the
      concentration in the nutrient medium is increased by 5mM prior to the transfer to
      a non-nutrient salts medium. All stages previously reported for the typical
      (M(3)cVII) strain of Physarum polycephalum from microplasmodia to spherules are
      seen but the mutant lacks the synchrony that the replacement technique induces in
      the typical strain. X-ray microanalyses locate calcium and phosphorus in granules
      in mitochondria and in the cytoplasm of specimens fixed without osmium.
      Mitochondria accumulate calcium-containing granules during early differentiation
      and appear to be essentially without granules in mature spherules. Mobilization
      of mitochondrial calcium is implicated in the initiation of differentiation. A
      longitudinally striated cytoplasmic inclusion is abundant in microplasmodia grown
      in media that have not been supplemented with additional calcium and is seen more
      rarely during calcium-induced spherulation. Whether or not this inclusion
      represents cytoplasmic contractile elements is unknown. The calcium-treated
      mutant strain, previously considered non-differentiating, may prove to be a good
      alternate model for the study of factors influencing differentiation. It was
      employed earlier as a control in studies of strains that readily spherulate in
      response to routine procedures.

PMID- 18620273
TI  - Immunoelectron microscopic localization of a fibronectin-like molecule in Dugesia
      lugubris s.l.
AB  - Fibronectin (FN)-like protein has been localized by immunoelectron microscopy in
      the extracellular matrix (ECM) of planaria Dugesia lugubris s.l. The
      immunolabeling was present in both intercellular spaces of epidermal cells and
      the basement membrane, however the amount and distribution of gold particles
      seemed to be substantially different. FN-like material increased markedly during
      the passage of migrating cells through the basement membrane from the parenchyma
      to the epidermis. Gold particles were often found at cell-matrix contacts. Our
      result suggest that FN-like molecules detected in planarian ECM may be involved
      not only in cell adhesion but also in promoting cell migration and in regulating
      the epidermal cell turnover.

PMID- 18620274
TI  - Anti-connectin monoclonal antibodies that react with the unc-22 gene product bind
      dense bodies of Caenorhabditis (Nematode) bodywall muscle cells.
AB  - Monoclonal antibodies, 3B9 and 4C9, specific to connectin (also called titin),
      3000 kDa elastic filamentous protein of vertebrate skeletal muscle, crossreacted
      with a high molecular weight protein (500 kDa) of the nematode Caenorhabditis
      elegans. However, its crossreactivity was weak to that of the unc-22 gene
      deficient mutant. Immunofluorescence showed that the antibodies stained both
      bodywall and pharynx muscles in the wild type, but only pharynx muscle in the
      mutant. Immunoelectron microscopy revealed that the antibodies bound to the dense
      bodies of bodywall muscle cells of the wild type but not to those of the mutants.
      In the pharynx muscles the localization of the antibodies was not clear in both
      normal and mutant worms. Moerman, D.G. et al. (Genes & Development 2, 93-105
      (1988) reported that the unc-22 gene product (500 kDa) is located in the A band
      of the bodywall muscle cells of C. elegans. Taking this information into
      consideration, it is suggested that the unc-22 gene product may be a qfilamentous
      protein linking a dense body and myosin filaments in the bodywall muscles of C.
      elegans.

PMID- 18620275
TI  - A putative new hydrostatic skeletal function for the epidermis in Monhysterids
      (Nematoda).
AB  - The ultrastructure of the epidermis of two Monhysterid nematodes (Geomonhystera
      disjuncta and Diplolaimella dievengatensis) is studied in detail. The epidermis
      is composed of discrete uninucleated cells. The cytoplasmic layer of the
      epidermis between the cuticle and the somatic muscles is very thin and contains
      bundles of filaments that attach the muscles to the cuticle. The epidermal chords
      are voluminous and contain the nuclei and most of the cell organelles. In the
      chords many large electron-transparent vacuoles are found. It is hypothesized
      that these vacuoles fulfill a function as a compartmentalised hydrostatic
      skeleton.

PMID- 18620276
TI  - An autoradiographic analysis of vitellogenin synthesis and secretion in the fat
      body of the stick insect Bacillus rossius.
AB  - The fat body of the stick insect Bacillus rossius was studied with a view to
      clarifying the metabolic pathway leading to secretion of vitellogenin (VG).
      Electrophoretic analysis of ovarian follicles and hemolymph from egg-laying
      females showed that the two tissues shared a common polypeptide composition
      consisting of five major polypeptides with molecular weights ranging from 60-180
      Kd. Following in vivo exposure to [(35)S]-methionine for up to 24 h, these
      polypeptides were labeled in a stage- and time-dependent manner, suggesting that
      they were transferred from the hemolymph to the oocyte during vitellogenesis. Fat
      body pulse-labeled with [(35)S]-methionine for up to 240 min and
      immunoprecipitated with an anti-yolk serum was labeled only in a fraction
      containing high molecular weight polypeptides. We presume these polypeptides to
      be VG precursors bearing a precursor-product relationship with the five major
      polypeptides of the hemolymph and developing ovarian follicles. Fat body exposed
      in vivo to [(3)H]-leucine for time intervals ranging from 20-240 min were
      processed for EM autoradiography. The results of this analysis showed that
      incorporated radioactivity was progressively transferred from the endoplasmic
      reticulum to the Golgi apparatus and from there to the composite granules. The
      data provided in this study are consonant with previous findings by which
      composite granules were shown to contain two compartments differing both in
      content and origin. In addition, the autoradiographical data of in vivo labeled
      fat body demonstrate that only the material partitioned into the electron-dense
      compartment of these granules is exocytosed.

PMID- 18620277
TI  - Hemocytes contribute to both the formation and breakdown of the basal lamina in
      developing wings of Manduca sexta.
AB  - Monoclonal antibodies (MAbs) raised against wing tissues of Manduca sexta
      recognize epitopes shared by both hemocytes and basal laminae. During the last
      larval stadium, the basal lamina of moth wing epithelium forms after hemocytes
      have migrated into the space adjacent to basal surfaces of epithelial cells. As
      adult development commences, hemocytes participate in phagocytosis of the same
      basal lamina; and as dissolution of the basal lamina proceeds (day 2-day 5 post
      pupation), wing epithelial cells send forth long basal processes and rearrange
      within the plane of the epithelium. During this period of cell rearrangement, the
      immunoreactivity of the basal lamina decreases in concert with an increase in
      immunoreactive vesicles within hemocytes; and at the ultrastructural level,
      hemocytes have been observed to engulf fragments of basal lamina. The
      distribution of immunolabel in the developing moth wing suggests that hemocytes
      contribute not only to the formation of the wing's basal lamina but also to its
      breakdown. Since basal laminae are probably important determinants of epithelial
      form and pattern, hemocytes also contribute to the shaping of epithelial
      populations.

PMID- 18620278
TI  - FMRF-amide immunoreactivity in a moth larva (Heliothis zea): The cerebral nervous
      system.
AB  - The cerebral nervous system of the larval corn earworm, Heliothis zea, was
      examined using light microscopy and immunocytochemistry. Immunoreactivity for the
      molluscan cardioactive peptide FMRF-amide (FMRFa) is widely distributed. Staining
      is localized in perikarya and axons of the brain, subesophageal ganglion and
      first thoracic ganglion. Immunoreactive axons are also found in the frontal
      ganglion and the corpora cardiaca. Crossreactivity studies for FMRFa and bovine
      pancreatic polypeptide (BPP) demonstrate that (a) the immunoreactive material is
      more FMRFa-like than BPP-like and (b) the antigenic material is heterogeneous.
      For animals on different feeding regimens, immunocytochemical surveys and
      radioimmunoassay suggest the observed variation in immunoreactivity among
      individuals is unrelated to feeding state.

PMID- 18620279
TI  - The secretory pathway of vitellogenin in the fat body of the stick insect
      bacillus rossius: An ultrastructural and immunocytochemical study.
AB  - The fat body of the adult female stick insect Bacillus rossius was examined
      ultrastructurally with a view to clarifying the secretory pathway. The absence of
      lipid storage in the tissue allowed visualization of a polarized distribution of
      all organelles in the cell cytoplasm. Composite granules were distributed along
      the baso-apical axis of the cell according to progressive stages of maturation.
      At their final stage of maturation, these granules possess two distinct
      compartments, an electron-translucent compartment and a more electron-dense one.
      The origin of each of the two compartments was traced back to other organelles in
      the basal cytoplasm of the fat body cell. The differential origin of the two
      compartments contributing to the composite granules was further investigated by
      cytochemical analyses. Vitellogenin was detected both in the electrondense
      compartment of the composite granules and in the Golgi apparatus. The electron
      translucent compartment of the composite granules appeared to consist mainly of
      urate crystals. Such enzyme activities as acid phosphatase, peroxidase and
      catalase were also detected in this latter compartment. The observations support
      the interpretation that secretion in the fat body of B. rossius entails fusion of
      Golgi-derived vesicles with a specialized kind of multivesicular body. While
      Golgiderived vesicles convey their load of newly synthesized vitellogenin to the
      electron-dense compartment, the multivesicular body develops the urate crystals
      of the electron-translucent compartment.

PMID- 18620280
TI  - Ultrastructural and histochemical investigations of peripatus integument.
AB  - The integument of Euperipatoides leukarti (Onychophora) has been studied by SEM
      and TEM-histochemical techniques. The thin (2-3 mu) cuticle is essentially
      arthropodan in design, comprising a thin, lamellate outer epicuticle, a
      homogeneous inner epicuticle, and an extensive fibrous procuticle. Five tanned
      lipoprotein lamellae constitute the outer epicuticle, the innermost showing a
      cross-striated pattern and the outermost also containing carbohydrates. The inner
      epicuticle contains untanned lipoproteins. The chitin-protein composite
      procuticle reveals a fibrous ultrastructure but no trace of helicoids. Distally
      it may be tanned, producing a sclerotin layer (exocuticle), pronounced in the
      sensory setae, claws and mandibles. Penetrating the epicuticle and extending into
      the procuticle are numerous, minute pore canals through which mobilised
      procuticle is resorbed prior to ecdysis. Beneath the procuticle is a monolayered
      epidermis traversed by tonofibrils and containing dense pigment granules. The
      membrane junctions are strongly convoluted and include an apical zonula adherens,
      septate desmosomes and a proximal lymph space. The epidermis is underlain by a
      thick (5-25mu) basement membrane of helicoidally organised collagen fibres.
      Functional and phylogetic implications of the integumental structure are
      discussed. Arthropod affinities are clear and the Onychophora should be included
      in that phylum if it is to be retained in modern taxonomic nomenclature.

PMID- 18620281
TI  - Dynamic role of microvilli in peritrophic membrane formation.
AB  - Although the peritrophic membrane (PM) is a common extracellular construction in
      many invertebrate groups, evidence of the location of its secretion has never
      been reported. In this study a specific marker for chitin has been developed,
      enabling a separate examination of secretion of the chitinous and proteinaceous
      components of the PM in the millipede, Glomeris marginata. Chitin appears first
      at the base of the microvilli (MV), synchronized in adjacent cells along the
      entire length of the midgut. Evidence showing that it originates at the plasma
      membrane is discussed. Proteinaceous components appear to be added from the MV to
      the chitinous sheet as it moves along the MV toward the lumen. Precedence for
      such a dynamic role for MV in formation of extracellular structures is reviewed.
      The completed PM extends around individual items in the gut contents as well as
      forming a multilayered envelope; this may enhance both its digestive and
      protective functions.

PMID- 18620282
TI  - Novel cnidocysts of narcomedusae and a medusivorous ctenophore, and confirmation
      of kleptocnidism.
AB  - Cnidocysts have been examined from the tentacles of the ctenophore Haeckelia
      rubra (Euchlora rubra) and five species of hydrozoan narcomedusae (Solmundella
      bitentaculata, Aegina citrea, Solmissus marshalli, Solmissus albescens, and
      Cunina sp.) using TEM, both in sections and by firing whole cnidocysts onto EM
      grids. The study revealed that these apotrichous isorhiza cnidocysts have a novel
      morphology in which the intracapsular inverted tubule has five circumferential
      pleats when viewed in transverse section, rather than the usual three pleats.
      Accordingly, the definition of helicoptychoneme cnidocysts has been broadened to
      include both the usual three-pleated cnidocysts and these new five-pleated
      cnidocysts. In general, apotrichous isorhizas have subspherical capsules with a
      thick, bilayered wall, whose interior is nearly filled with the regularly coiled,
      helically folded, five-pleated inverted tubule. Upon discharge, the everted
      tubule is several mm long and the five circumferential pleats become manifested
      as five helical rows of spines running up the tubule, which has three
      morphologically different segments. The very short basal segment is devoid of
      ornamentation; the remaining proximal portion is characterized by five spirals of
      uniform, closely packed short spines; the long distal portion is characterized by
      a single spiral of regularly spaced large spines that derive from all five
      spirals-the five spirals are otherwise demarcated in the distal portion by
      'scales' that are visible only with the electron microscope.

PMID- 18620283
TI  - Cytochemical localization of calcium in renal sac nephrocytes of Helix aspersa.
AB  - In renal sac nephrocytes of Helix aspersa, intracellular calcium has been
      localized using the oxalate-pyroantimonate (OPA) and phosphate-pyroantimonate
      (PPA) methods. Pyroantimonate precipitates are preferentially localized in the
      excretory spherule and in vesicles located in the basal and lateral regions of
      the nephrocyte. Such vesicles appear to release their content into the excretory
      vacuole. Calcium may interact with diverse types of molecules present in the
      excretory vacuole, thus favouring stabilization and packaging of the excretory
      spherule.

PMID- 18620284
TI  - Adult insect glial culture: Activation, substrate effects and proliferation.
AB  - Glial cells from an adult insect, Periplaneta americana, have been grown in
      neurone-free cultures. No growth occurred from freshly-excised fragments of
      abdominal nervous connectives. Vigorous growth was obtained, however, from
      explants of connectives induced to proliferate by prior exposure to a toxin,
      ethidium bromide, applied selectively to glial cells in vivo. Glial growth in
      vitro is dependent upon the initiation of early stages of repair in vivo: this
      supports the idea that haemocytes which invade the lesion zone immediately after
      damage are involved in directing proliferation of perineurial and sub-perineurial
      glia. In contrast, both glial and neuronal cells grew in vitro from explanted
      abdominal ganglia without prior glial lesioning, indicating that different
      factors may determine cellular regeneration in this domain. The morphology of the
      proliferating cells was influenced by the substrate; extensive glial migration
      was restricted to areas of close contact between cell and substrate surface.

PMID- 18620285
TI  - Ultrastructural investigations on the muscular systems in the barnacle,
      Tetraclita squamosa japonica.
AB  - Four muscular systems of the Tetraclita squamosa barnacle were observed by means
      of an electron microscope and it was revealed that these systems each bore
      different types of muscle cells. The four systems were the adductor (A), the
      lateral scutal depressor (LSD), the ventral scutal depressor (VSD), and the
      tergal depressor (TD). The A-system included cross stiated muscle cells which
      showed long sarcomeres (about 10 mum) and rather disordered arrays of
      myofilaments. The LSD-system included cross striated muscles which had medium
      length sarcomeres (about 6.7 mum) and rather ordered myofilamental arrays. The
      VSD-system was constructed of cross striated muscle cells which bore shorter
      sarcomeres (4.6 mum) than the previous three systems and ordered myofilamental
      arrays. This last type of cell also bore well-developed sarcoplasmic reticular
      systems. The TD-system included smooth muscle cells which showed rather ordered
      arrays of myofilaments and dense-bodies. Each muscular system, as described
      above, included to its advantage one type of cross striated or smooth muscle cell
      for its characteristic contraction. The relations between ultrastructures and
      functions of each muscular system will now be discussed.

PMID- 18620286
TI  - Mode of formation of the flight muscles in a butterfly Pieris brassicae.
AB  - The formation and development of the dorsal longitudinal flight muscles of the
      butterfly Pieris brassicae L have been studied by electron and light microscopy.
      These imaginal muscles arise from two symmetrical pairs of mesothoracic larval
      muscles, which are morphologically indistinguishable from the other wall muscles
      at the beginning of the 5th larval instar. However, 2 days before the end of this
      instar an accumulation of myoblasts is observed at the median region of these
      muscle fibres. The muscle fibres are penetrated by the myoblasts and broken into
      fragments. Progressive dedifferentiation of the larval fibrillar material in each
      of the muscle fragments is observed during the first days of the pupal
      development. The myoblasts within the basal lamina of the original larval muscle
      fibres remain associated with the muscle fragments. Myoblasts then fuse with the
      larval muscle fragments, which simultaneously fuse with each other. This results
      in the formation of rudimentary imaginal muscle fibres. The development of these
      fibres, particularly myofibrillogenesis, is studied until the emergence of the
      imago.

PMID- 18620287
TI  - The development of epidermal feet in preparation for metamorphosis in an insect.
AB  - Insect epidermal cell surfaces can be seen by scanning electron microscopy after
      removal of the basal lamina. This let us study surface changes in the 5th larval
      stage of Calpodes ethlius (Lepidoptera, Hesperiidae) in preparation for
      metamorphosis at the end of the stadium, in particular changes in the basal cell
      processes or feet, intercellular lymph spaces, filopodia and hemidesmosomes. The
      feet develop in three phases, initiation, elongation and contraction. Initial
      growth begins immediately after ecdysis and continues until commitment to
      pupation 66 hr later. During this phase the feet are randomly oriented.
      Elongation and orientation begin after commitment to pupation. Orientation is
      probably achieved by selective survival and growth of those feet that are axially
      oriented rather than by reorientation. As the larva shortens to the pupal form
      late in the stadium, contraction of the feet occurs and the cells become
      columnar. The feet finally disappear as the cells rearrange themselves into new
      positions in the pupal epidermis. The lateral margins of the feet are united by
      adhesions even when their interdigitations are most complex. The adhesions
      separate an intercellular lymph space from the haemolymph. The lymph space
      remains small through most of the stadium, but enlarges with the loss of lateral
      junctions as the feet contract and eventually extends along most of the length of
      the columnar cells. Filopodia then form and span the gaps between the cells as
      though they have been induced by the separation and loss of lateral cell to cell
      contact. Scanning electron microscopy also shows that hemidesmosomes reflect the
      axial alignment of the cells even before the orientation of the feet. The
      hemidesmosome plaques are linear structures having a constant width of 0.15 - 0.2
      mum and variable length. They arise in short sections and lengthen by the linear
      addition of more sections with the same width. Late in the stadium they lose
      their axial alignment and may become branched.

PMID- 18620288
TI  - Protein synthesis in vitro in cultures of the subepidermal adipose tissue and the
      ovary of the shrimp Penaeus semisulcatus.
AB  - In vitro culture systems were developed for subepidermal adipose tissue (SAT) and
      ovary of the shrimp Penaeus semisulcatus. Both tissues were cultured in sea water
      based media buffered with HEPES to pH 7.4 in an oxygen enriched atmosphere.
      Various incubation conditions were tested in order to define those supporting
      optimal rates of protein synthesis. Best results for de novo protein synthesis
      were obtained when amino acids and other supplements were added according to
      Landureau's medium composition for the SAT and Eagle's MEM for the ovary.
      Streptomycin was found to inhibit protein synthesis in SAT cultures. These in
      vitro systems are appropriate for future studies of serum lipoprotein synthesis
      and its hormonal control.

PMID- 18620289
TI  - Peroxisomes of the midgut epithelium, malpighian tubules and fat body of larvae
      of the dragonfly, Aeshna cyanea.
AB  - The enterocytes of the midgut epithelium of Aeshna cyanea larvae are rich in
      peroxisomes while the nidal regenerative and endocrine cells contain only a few.
      Most of the enterocytic peroxisomes are microperoxisomes lacking a crystalloid
      nucleoid, but peroxisomes with well developed nucleoid are also present. The
      peroxisomes are usually concentrated in the basal region of the cells but may
      also spread into the apical region and closely intermingle with absorptive lipid
      droplets. They significantly increase in number, when the larvae are regularly
      fed lipid-rich natural food or long-chain monounsaturated fatty acids that are
      unusual dietary components of these animals. This observation seems to indicate
      that the enterocytic peroxisomes are involved in chain shortening and degradation
      of fatty acids absorbed from the gut lumen. Numerous microperoxisomes are also
      present in the lipid-storing cells of the Malpighian tubules and fat body.

PMID- 18620290
TI  - Demonstration of bone resorbing cells in elasmobranchs: Comparison with
      osteoclasts.
AB  - We have previously shown that Elasmobranchs-characterized by a partially
      calcified cartilaginous endoskeleton-presented a bony vertebral arch containing
      osteoblasts, osteocytes and resorbing cells. The aim of this study is to test the
      ability of Elasmobranchs to resorb bone tissue. The subcutaneous implantation in
      dogfish (Scyliorhinus canicula) of devitalized mineral-containing bone particles,
      obtained from a bony fish (the eel, Anguilla anguilla) resulted, after 21 2
      months, in the formation of mononucleated as well as multinucleated cells around
      and between the bone fragments. By light microscopy, the multinucleated giant
      cells presented the general aspect of osteoclastic cells whereas, by transmission
      electron microscopy they never showed ruffled borders which are considered as the
      typical features of osteoclasts. Except for this character, the mononucleated and
      multinucleated cells exhibited the typical ultrastructural aspects leading us to
      say that these cells are involved in the resorption of the bone fragments. This
      study shows that Elasmobranchs are able to resorb implanted bone.

PMID- 18620291
TI  - Ultrastructural and histochemical aspects of zinc accumulation by fish scales.
AB  - The effect of zinc exposure on the ultrastructure of the scales and scale
      associated cells of the estuarine teleost, Fundulus heteroclitus was investigated
      in laboratory experiments. The Timm sulfide silver stain indicated that in the
      calcified region of the scales, Zn was colocalized with the calcium phosphate
      mineral crystals. X-ray diffraction analysis showed that Zn did not have an
      effect on crystal structure. The scale osteoblasts of Zn-exposed fish showed an
      increase in the number of lysosome-like structures contained by the cytoplasm. In
      Zn-exposed animals, X-ray microanalysis revealed that these structures contain
      greatly increased levels of zinc and sulfur relative to controls. In all
      specimens, the lysosomes contained higher levels of Zn than either the
      surrounding cytoplasm or adjacent scales. The findings suggest that osteoblast
      lysosomes may be involved in the accumulation of Zn and other metals by fish
      scales by the enzymatic degradation of metallothioneins or other metal-binding
      proteins. This could represent an important mechanism for the detoxification of
      excess heavy metal ions taken up from the environment and the metabolism of
      essential metals by calcified tissues.

PMID- 18620292
TI  - Intercellular junctions during development of the definitive kidney in lampreys:
      freeze fracture and morphometric analyses.
AB  - The changing morphology of intercellular junctions in renal morphogenesis during
      lamprey metamorphosis was followed using freeze-fracture replicas and
      morphometry. Gap junctions and particle aggregates among strands of occluding
      junctions are conspicuous in the differentiating podocytes of the renal corpuscle
      and in the early ciliated neck and proximal segments but not in the distal
      segment. The cells of the segmented nephron arise from alpha nephrogenic cells
      which have a focal aggregate (macula occludens) of 4.8 junctional strands. Upon
      the initiation of metamorphosis the number of strands increases to 8 in
      undifferentiated cells with either maculae or zonulae occludentes.
      Differentiation of both neck and proximal segments is accompanied by gradual
      transformation of a 7-strand zonula occludens to a 4-strand junction but it
      becomes more shallow in the latter segment. Two types of undifferentiated cell
      are recognized through five of the seven metamorphic stages. Cells of two types
      of distal segments begin differentiation at the midpoint of transformation and
      immediately show zonula occludens of different morphology. Distal segment I (pars
      recta) has 5 strands and a 0.250 microm depth whereas segment II has 8-9 strands
      with twice the apical-basal depth. The larval archinephric duct undergoes a
      moderate transformation in junctional morphology with the addition of 2 strands
      and no increase in apical-basal depth in zonulae occludentes during
      metamorphosis. Changes and development of types of intercellular junctions along
      the nephron in lampreys are discussed with reference to known regional functional
      specialization in this organism and with the morphology of renal tubular
      intercellular junctions in other vertebrates.

PMID- 18620293
TI  - Ultrastructural features of egg development in oviparae of the vetch aphid,
      Megoura viciae buckton.
AB  - In the ovaries of the oviparous morph of the aphid, Megoura viciae, resting
      oocytes are located in the basal region of each germarium. During previtellogenic
      egg development, electron-dense spheres appear in the ooplasm. During
      vitellogenesis a brush border develops at the oolemma, and numerous protein and
      lipid-like spheres accumulate in the egg cytoplasm. Follicle cells are of two
      morphologically distinct types, termed 'type 1' and 'type 2' follicle cells.
      Unlike the more numerous 'type 1' cell, 'type 2' cells do not become patent. The
      acellular tunica propria exterior to follicle cell apices remains intact
      throughout egg development. During late vitellogenesis symbiont invasion of eggs
      takes place via 'receptor' cells encircling the pedicel at the posterior egg
      pole. These cells shrink and/or degenerate to create intercellular spaces that
      facilitate symbiont transmission. The end of vitellogenesis is marked by
      vitelline membrane formation and secretion of the chorionic layers, at which time
      the next egg in the ovariole undergoes final stages of previtellogenic growth and
      enters vitellogenesis.

PMID- 18620294
TI  - Differentiation and function of chorioallantoic cells in avian surrogate eggs.
AB  - Embryos of the domestic fowl have been successfully reared in turkey eggshells.
      The development of the Chorioallantois and its fusion to the shell membranes has
      been studied ultrastructurally and compared with the calcium transporting ability
      of normal embryos. There is no evidence of any species-specific effects in this
      functional association. The use of surrogate eggshells provides an interesting
      opportunity to study the differentiation and physiological properties of the
      chorioallantois.

PMID- 18620295
TI  - Ultrastructural spermatid and sperm morphology in Poecilocerus pictus (Fab.) with
      a reference to spermeiophagic cells in the testis and sperm duct.
AB  - Electron microscopical studies were carried out on spermatid and sperm structure
      in P. pictus. The spermatid nuclear envelope possesses pores and is surrounded by
      microtubules which disappear on metamorphosis to sperm though centriolar adjunct,
      and its corresponding centriole comprising the basal body for flagellum. remains
      persistent in both. The mitochondria are arranged as two fused bodies with
      prominent cristae flanking the central axoneme and also contain curved end feet.
      In axoneme the microtubular complex is comprised of 9 + 9 (doublet) + 2 tubules +
      nine coarse fibres and also reveals nine radial links with electron-dense link
      heads. In P. pictus an alteration in temperature range, ambient for its rearing
      and generation of fertile spermatozoa, induces the production of sterile sperms
      which are characterized by multiple axonemes and mitochondrial bodies engirdled
      by a common plasma membrane. Presence of phagocytic cells is also an essential
      feature of its testis and vas deferens. These spermeiophagic cells engulf the
      neighbouring spermatozoa as evidenced by the fragments of axoneme, nuclei, and
      acrosomes in their cytoplasm.

PMID- 18620296
TI  - Transmission of symbiotic algae through sexual reproduction in hydra: movement of
      algae into the oocyte.
AB  - The histological pathway by which intracellular symbiotic Chlorella move into the
      developing oocytes of hydra was investigated at the ultrastructural level. Algae
      move from within the digestive cells of the endoderm to within the oocytes of the
      ectoderm in a three-step process. First, the algae are released by digestive
      cells into the mesolamella (basement membrane). Second, the algae move as
      individual cells into the adjacent intercellular spaces of the ectoderm. Third,
      they are taken up by the oocyte by phagocytosis. This transfer occurs only in the
      central regions of the ovary, and only after oocytes have reached an advanced
      stage. Normally the mesolamella is separated from the ectodermal interstitial
      spaces by a layer of epitheliomuscular cell muscle processes. This layer
      degenerates in the region where algae will move into the ectoderm. This study
      shows that algae move as individual cells and not intracellularly within
      processes of the epithelial cells.

PMID- 18620297
TI  - Spatial and temporal variations in cuticle proteins as revealed by monoclonal
      antibodies. Immunoblotting analysis and ultrastructural immunolocalization in a
      beetle, Tenebrio molitor.
AB  - A library of monoclonal antibodies (Mabs) against adult cuticle of Tenebrio was
      used to visualize the secretion of cuticular antigens during metamorphosis.
      Immunoblots of water- and urea-soluble proteins, and high resolution immunogold
      labelling has shown that, except in one clone, the Mabs recognize antigens in the
      three developmental stages. However, the MW of larval and pupal antigens are
      different from the adult ones, though sharing common epitopes. Blots of cuticle
      proteins (CPs) bound to different lectins shown few water-soluble glycosylated
      proteins weakly or not recognized by the Mabs, suggesting that the majority of
      the Mabs do not recognize glycosylated epitopes. The immunolocalization of the
      different antigens suggests a molecular basis for both developmental and regional
      variations in cuticular architecture and to the modifications due to
      sclerotization, which differ between pre- and postecdysial cuticles of the three
      developmental stages.

PMID- 18620298
TI  - A periodic structure in the 'pen' chitin of the squid Loligo vulgaris.
AB  - The organization of the chitin-proteoglycan in Loligo vulgaris pen was examined
      ultrastructurally and related to the molecular order indicated by X-ray
      diffraction. There is a centrosymmetric striated repeat of 22 nm in the system
      which is based upon dark and light bands of unequal width. The banding is
      orientated perpendicular to the direction of the major molecular axis of the
      chitin fibres. The chitin molecules are laid down in sheets with a mutual, though
      irregular, twist to produce a laminated 'plywood' material.

PMID- 18620299
TI  - Origin and development of the dorso-ventral flight muscles in Chironomus
      (Diptera; Nematocera).
AB  - The origin and development of the dorso-ventral flight muscles (DVM) was studied
      by light and electron microscopy in Chironomus (Diptera; Nematocera). Chironomus
      was chosen because unlike Drosophila, its flight muscles develop during the last
      larval instar, before the lytic process of metamorphosis. Ten fibrillar DVM were
      shown to develop from a larval muscle associated with myoblasts. This muscle is
      connected to the imaginal leg disc so that its cavity communicates with the
      adepithelial cells present in the disc; but no migration of myoblasts seems to
      take place from the imaginal leg disc towards the larval muscle or vice versa. At
      the beginning of the last larval instar, the myoblasts were always present
      together with the nerves in the larval muscle. In addition, large larval muscle
      cells incorporated to the imaginal discs were observed to border on the area
      occupied by adepithelial cells, and are probably involved in the formation of 4
      other fibrillar DVM with adepithelial cells. Three factors seem to determine the
      number of DVM fibres: the initial number of larval fibres in the Anlage, the
      fusions of myoblasts with these larval fibres and the number of motor axons in
      the Anlage. The extrapolation of these observations to Drosophila, a higher
      dipteran, is discussed.

PMID- 18620300
TI  - Unusual organization of the tropharium in the telotrophic ovarioles of an insect,
      Saldula saltatoria.
AB  - The tropharium of the common shorebug Saldula saltatoria consists of 2 zones: the
      apical mitotic region and the distal one comprising numerous mononucleate nurse
      cells. Each individual nurse cell is connected to the centrally located trophic
      core by a thin cytoplasmic projection referred to as a trophic process. The
      accumulations of a dense material interpreted as the remnants of intercellular
      bridge rim are observed associated with the trophic process membrane. In the
      light of these results the establishment of telotrophic ovarioles in hemipterans
      is discussed.

PMID- 18620301
TI  - The double nucleus of the sertoli cell in the lizard Anolis carolinensis.
AB  - Over 90% of the Sertoli cells in the testes of adult lizards (Anolis
      carolinensis) are binucleate. The nuclei occur in closely associated pairs in the
      basal cytoplasm of the Sertoli cells that line the testis tubules. The two nuclei
      of a pair are of similar volume, and each usually contains one conspicuous
      rounded nucleolus. The average volume of individual nuclei varies from 367.8
      microm(3) in spermatogenically active testes in March to 172.5 microm(3) in
      September, when testes are regressed. The irregular shape of the Sertoli nuclei
      is particularly pronounced during testicular regression. Until initiation of
      spermatogenesis in hatchling lizards, Sertoli cells have a single nucleus
      containing patches of hetcrochromatin. With the appearance of prophase stages of
      primary spermatocytes, a few paired Sertoli nuclei can be found, and the nuclei
      increasingly exhibit the homogeneous euchromatic nucleoplasm of the adult. The
      average volume of individual nuclei in lizards under 4 months of age is less than
      a third the volume of Sertoli nuclei in reproductively active adults. The
      appearance of binucleate cells at this time documents a doubling of the amount of
      desoxynucleic acid in Sertoli cells preparatory to their growth and expanded
      functions during spermatogenesis.

PMID- 18620302
TI  - The properties of the lining membrane of the insect tracheal system.
AB  - In the surface layer of the lining cuticle of the tracheae of adult Calliphora
      there is no sign of any waterproofing layer of cuticulin (sclerotin + lipid) as
      seen in the surface of the general body cuticle. In a few insects: Calliphora
      adult thorax, Rhodnius adult tracheae serving the ovary, Periplaneta abdominal
      tracheae, it has been possible to introduce silver hydroxide solution into the
      lumen of tracheae in the living insect. In each case the silver hydroxide reacted
      at room temperature with the argentaffin structures in the cuticle, as happens in
      the soft surface cuticle of Rhodnius larva before moulting or after gentle
      abrasion. In the thorax of Calliphora the taenidia of the tracheae are stiffened
      by argentaffin cuticulin. but immediately upon entering the cleft in the flight
      muscle the taenidia disappear and are replaced by simple folds, so that no stiff
      taenidia enter the muscle and there is no argentffin material deeper in the
      flight muscle system.

PMID- 18620303
TI  - The direct transport of oxygen in insects by large tracheae.
AB  - Vast numbers of large and small tracheae in the abdomen of adult Calliphora are
      so modified that they can transfer oxygen directly by diffusion to the developing
      ovaries. Tracheoles are scarce but. instead, a system of distended tubules,
      evaginated into the cytoplasmic surface of the trachea, cover the entire tracheal
      surface with permeable tubes diffusing oxygen to the developing tissues. A
      similar development occurs also in the male fly.

PMID- 18620304
TI  - Sensory organs in a cavernicolous insect after cryofixation without
      cryoprotectants: a comparative ultrastructural study.
AB  - Three different sensory organs (one mechanoreceptor, one chemoreceptor and one
      chemo-mechanoreceptor) of the antennae of the cavernicolous Coleoptera Speonomus
      hydrophilus and S. zophosinus have been compared by means of electron microscopy
      after chemical fixation or cryofixation without cryoprotectant; when cryofixation
      succeeds, cells and organelles have a different appearance from the chemically
      fixed ones: they have rounded and smooth outlines and are more electron-dense;
      some very fine details, such as tubuline sub-units of microtubules, are
      perceptible after cryofixation only. However, chemical fixation gives much more
      reproducible results than cryofixation; moreover, when good cryofixation is
      achieved preservation of cells and organelles is satisfactory only for the
      peripheral region; large ice-crystals more or less destroying the central zone,
      except the nerves. In short, chemical fixation and cryofixation appear as
      complementary techniques: chemical fixation must be used as a routine fixation
      and cryofixation when specially good cell and molecular preservation must be
      achieved for peripheral tissues only.

PMID- 18620305
TI  - High titers of ecdysteroids are associated with the secretory process of
      embryonic envelopes in the european lobster.
AB  - The newly laid egg of the lobster Homarus gammarus is surrounded by a vitelline
      coat. Just after fertilization, a new subjacent envelope (2), originating from
      the cortical reaction, is deposited beneath the vitelline coat. In the course of
      embryonic development, five new coatings (envelopes 3 to 7) are secreted
      successively from the ectodermal embryonic cells. These will remain until
      hatching, freeing the mysis larva in concentric order without exuviation. The
      concentration of both the two major ecdysteroids (ponasterone A and 20
      hydroxyecdysone) and their respective precursors (25-deoxyecdysone and ecdysone)
      were determined as a function of the secretory phase for three embryonic
      envelopes (2, 3 and 6). We determined that the secretory processes proceed in the
      presence of high titers of 20-hydroxyecdysone during the onset of envelope
      secretion and of ponasterone A in the last phase of secretion.

PMID- 18620306
TI  - Morphogenesis of the antenna of the male silkmoth, Antheraea polyphemus. I. The
      leaf-shaped antenna of the pupa from diapause to apolysis.
AB  - The antenna of the male silkmoth Antheraea polyphemus is a featherlike structure
      consisting of a central stem and ca. 120 side branches, which altogether carry
      about 70,000 olfactory sensilla. We investigate the development during the pupal
      phase. At the end of diapause, the antennal rudiment consists of a leaf-shaped,
      one-layered epidermal sac. It is supplied with oxygen via a central main trachea,
      which gives off numerous thin side branches. These are segmentally arranged into
      bundles which run to the periphery of the antennal blade. When the epidermis
      retracts from the pupal cuticle (apolysis; stage 1), it consists of cells which
      are morphologically uniform. The epidermal cells form a network of long,
      irregular basal protrusions (epidermal feet), which crisscross the antennal
      lumen. During the first day post-apolysis (stage 2), the antennal epidermis
      differentiates into alternating thick 'sensillogenic' and thin 'non
      sensillogenic' areas arranged in stripes which run in parallel to the tracheal
      bundles. Numerous dark, elongated cells, which might be the sensillar stem cells,
      are scattered in the sensillogenic epithelium. A number of very early sensilla
      has been found at the distal edges of the sensillogenic stripes in positions
      which later will be occupied by sensilla chaetica. The whole antennal blade is
      enveloped by the transparent ecdysial membrane, consisting of the innermost
      layers of the pupal cuticle which are detached during apolysis.

PMID- 18620307
TI  - Intercellular junctions in myriapods.
AB  - Tissue from the intestinal tract of myriapods, including millipedes, centipedes
      and pauropods were examined in tracer-impregnated sections and freeze-fracture
      replicas. The foregut and hindgut of all three classes exhibit pleated septate
      junctions; these display undulating intercellular ribbons in thin sections. In
      replicas they show discrete intramembranous particle (IMP) arrays aligned in rows
      in parallel; with one another. The tissues of the hindgut also possess
      scalariform junctions, characterized by cross-striated intercellular clefts in
      sections and IMP-enriched membranes in replicas. Gap junctions occur in all
      groups, but they are atypical in replicas in that their component IMPs do not
      always fracture onto the E face, as is characteristic of other arthropods; some
      IMPs cleave to the P face and others to the E face. The midgut of these organisms
      exhibits smooth septate junctions with conventional straight septal ribbons and
      occasional interseptal columns. However the intramembranous appearance in
      replicas is variable, particularly in centipedes, in that the rows of IMPs in
      chemically-unfixed propanecryofixed tissues, are prominent and adhere
      preferentially to the E face, with complementary P face grooves, while in fixed
      tissues the IMPs are much less distinct and fracture to either P face or E face.
      They tend not to protrude far beyond the mid-plane of the membrane bilayer and
      lie in rows which commonly take on the form of a network. Individual rows of the
      network sometimes curve to run beside a second row, over a short distance, before
      bending away into another part of the network. The aligned particle rows, which
      are much more prominent in millipedes, where they frequently lie in close
      parallel appositions, do not fuse into ridges as often occurs in insect tissues.
      The myriapod junctions, therefore, are of the same general kind as are found in
      the gut tract of other arthropod groups, but differ with respect to the
      subtleties of their intramembranous organization and disposition.

PMID- 18620308
TI  - Ultrastructural observations on chondroid bone in the teleost fish Hemichromis
      bimaculatus.
AB  - This paper presents transmission electron microscopical observations on the
      chondroid bone (CB) supporting the neurocraniad articulation facet of the upper
      pharyngeal jaws of juvenile specimens of Hemichromis bimaculatus (an acellular
      boned teleost fish). Chondroid bone, a skeletal tissue morphologically
      intermediate between cartilage and bone, is composed of a dense mineralized
      collagenous matrix, resembling that of woven-fibred bone, and large chondrocyte
      like cells. The latter vary considerably in their morphological features
      (functional cells, cells containing a large vacuole and degenerating cells). The
      CB is mineralized except for its upper layer. Mineralization is initiated in
      matrix vesicles. Clusters of apatite crystals coalesce at the mineralization
      front. Distally, the tissue grows by incorporation of cells which exhibit the
      features of osteoblasts, and which derive from less differentiated fibroblast
      like cells located in the outermost layer of the tissue. Proximally, the CB is
      subjected to erosion by multinucleated clastic cells. The deposition of bone
      against the wall of lacunae which have been opened by clastic resorption may
      suggest a possible active involvement of the CB cells. Further studies should
      point out whether this bone substantially contributes to the acellular dermal
      dentigerous bone located below.

PMID- 18620309
TI  - Scanning electron microscopic study of blood cell surfaces of the middle asian
      tortoise, Testudo horsfieldi.
AB  - The micromorphology and surface topography of spleen cells of the Middle Asian
      tortoise, Testudo horsfieldi, have been examined by scanning electron microscopy.
      Spleen cells comprise a population with surface characteristics similar to
      counterparts in mammalian spleen except for an, as yet undescribed, lymphocyte
      which is designated as lamellar type on the basis of its surface contours.

PMID- 18620310
TI  - Ultrastructure studies of the extracellular filaments in the ventral nerve of
      Panulirus argus.
AB  - The ventral nerve cord of the spiny lobster, Panulirus argus was examined by
      transmission and scanning electron microscopy. Tannic acid mordant stain was used
      to enhance extracellular filaments. The ventral nerve cord is surrounded by an
      unusual perineurial sheath composed primarily of interwoven extracellular
      filaments. Gap junctions were found associated with the glial cells making up the
      perineurium. The axo-glial wrappings also contained extracellular filaments
      associated in bundles rather than uniformly around the axons. The extracellular
      filaments of the perineurium and axo-glial wrappings appeared to be
      morphologically identical with diameters ranging from 10-15 nm.

PMID- 18620311
TI  - Seasonal patterns of ornithine decarboxylase activity and levels of polyamines in
      relation to the cytology of germinal cells during spermatogenesis in the sea
      star, Asterias vulgaris.
AB  - The activity of ornithine decarboxylase (ODC) and levels of polyamines were
      measured in the testes of Asterias vulgaris collected throughout an annual
      spermatogenic cycle. Samples of the testes were prepared for light and electron
      microscopy to observe the associated changes in the cytology of germinal cells.
      The specific activity of ODC increased at the onset of testicular growth,
      decreased during the coldest period of the winter when testicular growth was
      minimal, and increased again early in the spring when testes grew maximally.
      Increased activity of ODC resulted in increased levels of polyamines and was
      correlated with either mitotic or meiotic germinal cell divisions, or both.
      Spermine levels were always greater than putrescine, followed by spermidine.
      Highest levels of polyamine synthesis coincided with the onset of spermatogonial
      proliferation during the fall and with the period of meiotic differentiation and
      spermiogenesis in the spring. Mid-summer (July) testes were small (0.3-0.5 gonad
      index (GI)) and contained amitotic spermatogonia arrested in G(1) of the cell
      cycle. Mitotic and pre-meiotic testes (October/November) increased slightly in
      size (0.3-1.4 GI) and contained actively dividing spermatogonia, most of which
      differentiated into primary spermatocytes. Testes from February and March were
      large (1-6.75 GI), but the proliferative status of their spermatogonia and
      primary spermatocytes varied. Spermatogonia and primary spermatocytes from early
      February testes were not dividing. In testes obtained in March, both
      spermatogonial mitosis and meiosis of spermatocytes resumed, coincident with
      increased field water temperatures.

PMID- 18620312
TI  - A radioautographic study of collagen secretion in the dogfish nidamental gland.
AB  - Optical microscope and ultrastructural autoradiography have been used to localise
      the sites of collagen secretion in the gland zones, and track its cellular
      synthesis and mode of cellular secretion. Optical microscope observation has been
      done after (3)H proline injection into the gland. Untrastructural study has been
      achieved after applying the incubation method. Optical microscope study has
      demonstrated that all the gland zones were involved in the secretion of the
      collageneous protein, though some of them (the D zone and lamellae) secrete more
      collagen than the others. The ultrastructural study demonstrates that the forms
      of secretion are numerous: various-looking grains, whose elaboration follows the
      path of vertebrate collagen produced by fibroblasts, or grains whose only source
      is rER. The protein periodicity which is observed in the mature capsule (37 nm)
      is acquired only outside the cells, in the tubular or glandular lumen. It is
      possible that two types of collagen are secreted by the gland, the first forming
      the major part of the capsule wall, the other contributing to the plugs sealing
      the slits of dehiscence.

PMID- 18620313
TI  - Sem observations on the interfacial surface of the cement of the adult barnacle,
      attached to natural and synthetic adherends.
AB  - The barnacle, Chthamalus fragilis Darwin, is found attached to a variety of
      natural and man-made substrates in the marine environment. Bases of specimens of
      this species attached to the leaves and stalks of marsh grass, Spartina
      alterniflora, and to polyethylene films placed in the high intertidal zone of the
      marsh were studied by scanning electron microscopy in order to determine the
      interfacial features of the cement holding these animals in place. When removed
      carefully, the interfacial surfaces of the barnacle cement appeared as finely
      detailed replicas of the leaf surfaces and of the polyethylene film surfaces,
      mimicking the highly contoured surface features and peripheral interdigitations
      of the adjacent epithelial cells which compose the surfaces of the leaves and
      'crow's foot' and linear perturbations in the relatively smooth polyethylene
      films. These observations indicate that the bioadhesive secretion of this
      barnacle species loses its liquidity and becomes a hardened adhesive cement. It
      is probable that this mold-like replication of adherend surface details
      contributes to barnacle adhesion by mechanical interaction between the barnacle
      cement and the adherend surfaces.

PMID- 18620314
TI  - Differential fate of mitochondria during spermiogenesis in the ratfish
      Hydrolagus.
AB  - During spermiogenesis in the ratfish Hydrolagus colliei, spermatid mitochondria
      follow one of three fates. Some are retained as functional spermatozoan
      mitochondria clustered in the midpiece, some are enclosed in large vacuoles and
      phagocytosed by Sertoli cells, and the remaining mitochondria are segregated to
      the remnant cytoplasm. In the latter site rhodamine 123 fluoresence studies show
      that the mitochondrial derivatives, although much altered morphologically, retain
      the electrochemical gradient characteristic of the inner mitochondrial membrane.
      Some mitochondrial derivatives show activity even after the remnant cytoplasm is
      cast off from the spermatozoon.

PMID- 18620315
TI  - Ultrastructural features of degeneration of the gallbladder during lamprey
      biliary atresia.
AB  - Thin sections and freeze-fracture replicas were used to examine the fine
      structural features of degeneration of the gallbladder during lamprey biliary
      atresia. The cells of the epithelium undergo a progressive accumulation of dense
      bodies and vacuoles, loss of glycogen, condensation of the filamentous ectoplasm,
      fragmentation of microvilli, and dilation of cisternae of rough endoplasmic
      reticulum but eventually disappear by stage 4 of metamorphosis. Zonulae
      occludentes in the epithelium show a progressive increase in apical-basal depth
      as the junctional strands fragment. The possibility of an influence of
      transformed, subepithelial cells on degeneration of epithelial cells is suggested
      by close contact of the former with the thickened, highly pleated, epithelial
      basal lamina. The smooth muscle cells of the larval gallbladder are believed to
      transform during lamprey metamorphosis into these subepithelial cells which shed
      their external lamina, become intimately associated with collagen and other
      microfibrils, and which may be capable of phagocytosis. The events of gallbladder
      degeneration during lamprey metamorphosis show features of apoptosis.

PMID- 18620316
TI  - Ultrastructure of mitochondria in the corpora allata of honeybees infected by
      Nosema apis before and after treatment with anti-Nosema drugs.
AB  - Ultrastructural differences were observed among mitochondria from the corpora
      allata of healthy, Nosema-infected, and anti-Nosema drug treated honeybees.
      Mitochondria in the corpora allata of the healthy honeybees were large in size,
      possessed well defined membrane, numerous mitochondrial granules and less
      electron-dense matrix. In the corpora allata of Nosema-infected honeybees,
      mitochondria were small in size and the mitochondrial matrix had a higher
      electron density. Mitochondria from the corpora allata of Nosema-infected
      honeybees after treatment with thimerosal, had a lower electron density in the
      mitochondrial matrix and a larger diameter than those from untreated honeybees.
      Mitochondria from fumagillin-treated honeybees had the smallest diameter and the
      highest electron density in the matrix among mitochondria observed in the present
      study. Image analysis also confirmed the differences in the electron density of
      the mitochondrial matrix among mitochondria in the corpora allata of four
      experimental groups of honey bees.

PMID- 18620317
TI  - Ultrastructural differences of neurosecretion granules in the corpora cardiaca of
      the honeybee with and without infection by Nosema apis.
AB  - Axons of corpora cardiaca in the Nosema infected honeybees contained numerous
      tightly packed neurosecretion granules. These granules invariably possessed high
      electron densities. Neurosecretion granules of similar size were also observed in
      the axons of corpora cardiaca in the healthy honeybees. But these granules were
      shown to possess various electron densities. Image analysis revealed that some of
      these granules possessed an electron dense core, and the electron densities
      decreased gradually from the core, to the fringe of the granule. Some granules
      appeared to be completely broken down into fine granular substances, while others
      appeared to be completely broken down into finer particles. It is suggested that
      in the healthy honeybees, the releasing of neurosecretion from the corpora
      cardiaca had taken place normally, whereas in the diseased bee, the releasing
      mechanism had been blocked. The blockage is probably due to the infection.

PMID- 18620318
TI  - Ultrastructural changes in the secretion granules of the hypopharyngeal glands of
      the honeybee infected by Nosema apis and after treatment with fumagillin.
AB  - Electron-dense secretion granules were numerous in the hypopharyngeal glands of
      healthy honeybees. In the hyopharyngeal glands of honeybees infected by Nosema
      apis, these granules appeared to have increased in size and lost their electron
      density, possessing a core area that consisted of numerous smaller granules, and
      a slightly electron dense fringe area, which in some cases possessed a
      crystalline structure. In the hypopharyngeal glands of infected honeybees after
      treatment with fumagillin, the secretion granules were also large and slightly
      electron dense, but the granular content was homogenous. Some of these granules
      were also partially crystallized. These ultrastructural changes in the secretion
      granules of diseased and fumagillin treated bees, is probably associated with a
      change in secretory activity of the glands.

PMID- 18620319
TI  - Ultrastructural analysis on the gland secretion in the extracellular ducts of the
      hypopharyngeal glands of the honeybee infected by Nosema apis.
AB  - The hypopharyngeal glands of the honeybee secrete the larval food royal jelly,
      along with enzymes that are used in the production of honey from nectar. The
      composition of this secretion mixture varies with the physiological condition of
      the honeybee, and the final secretion mixture is conveyed through the
      extracellular ducts to the large excretory duct. The secretion products in the
      extracellular duct of both healthy and infected honeybees, was studied by
      transmission electron microscopy and image analysis. These products consisted of
      a densely packed, faintly visible granular substance. The granules were clearly
      defined by the computer enhanced image. The secretion products from the Nosema
      infected honeybees exhibited the same granular structure, but were much less
      concentrated, thereby reducing the overall electron density of the secretion.
      These observations suggest that the composition of the secretion products from
      the hypopharyngeal glands in the Nosema-infected honeybees, was altered
      considerably.

PMID- 18620320
TI  - Ultrastructure of the epidermal eyespots of an acoel platyhelminth.
AB  - The epidermal eyespots of the acoel Otocelis rubropunctata would appear to
      consist of a single cell type provided with pigment granules and cilia. Very
      numerous dictyosomes characterize the cytoplasm of the cells. The cilia possess
      the 9X2 + 2 pattern of microtubules and the typical rootlets of acoels.
      Microvilli are interspersed among the cilia. The basal surface of the cells seems
      to present synatpic input and to generate an axonal process, which would confirm
      their photosensitive role. The structural similarities with other photoreceptors
      are outlined.

PMID- 18620321
TI  - Regulation of air and blood flow through the booklungs of the desert scorpion,
      Paruroctonus mesaensis.
AB  - Injections of dye, latex and India ink were used to reveal the path of hemolymph
      circulation through the scorpion booklungs. Fine, branched arteries carry blood
      directly to muscle and other organs. The blood returns through venous channels to
      the ventral mesosoma where it passes laterally through the booklungs and into the
      pneumocardial veins just beneath the pleural cuticle. Blood flows dorsally
      through these veins to the pericardial sinus and heart. The scorpion has four
      pairs of booklungs located in the anterior segments of the ventral mesosoma. Each
      booklung has a spiracle which opens into an atrium enclosed by cuticular
      membrane. Air passes from the atrium into the booklung lamellae. Agitation of the
      animal or application of CO(2) causes retraction of the anterior and posterior
      atrial membrane. This expands the atrial chamber and allows gas exchange in the
      booklung lamellae. The posterior atrial membrane has a specialized region which
      forms a springy valve. This normally closes the spiracle unless pulled open by
      contraction of the attached poststigmaticus muscle. The pectens and receptors
      within the atrium may mediate the responses to CO(2). Slender hypocardial
      ligaments containing muscle fibers extend from the heart (dorsal mesosoma) to the
      booklungs in the ventral mesosoma. Heart movements thus cause dorso-ventral
      movement of the booklungs. The significance of these movements is as yet unclear.
      They may increase ventilation, help force blood to the heart and/or agitate the
      blood and booklung lamellae and thereby aid gas exchange. Passage of blood
      through the booklungs is regulated by dorsal and ventral muscles attached to the
      atrium at the lateral edge of the booklung. Contraction of the ventral atrial
      muscle closes the excurrent channel for passage of blood from the booklung into
      the pneumocardial vein. Electrical stimulation of the segmentai nerves from the
      subesophageal and first three abdominal ganglia causes spiracle opening and
      contraction of muscles attached to the atrial membrane. A previous study showed
      that these same segmental nerves also modulate heart activity. They thus provide
      a major pathway for regulation of the respiratory and circulatory systems.

PMID- 18620322
TI  - Primary culture of axolotl spinal cord ependymal cells.
AB  - In order to examine the role of ependymal cells in the spinal cord regeneration
      of urodele amphibians, procedures were established to identify and culture these
      cells. Cell isolation and culture conditions were determined for ependymal cells
      from larval and adult axolotls (Ambystoma mexicanum). Dissociated cells prepared
      from intact spinal cords were cultured on fibronectin- or laminin-coated dishes.
      Dissociated cells attached more rapidly to fibronectin, but attached and spread
      on both fibronectin and laminin. Essentially pure populations of ependymal cells
      were obtained by removing 2 week old ependymal outgrowth from lesion sites of
      adult spinal cords. These ependymal outgrowths attached and grew only on
      fibronectin-coated dishes. Growth and trophic factors were tested to formulate a
      medium that would support ependymal cell proliferation. The necessary peptide
      hormones were PDGF, EGF, and insulin. TGF-beta(1) affected the organization of
      cell outgrowth. Initially, longterm culture required the presence of high levels
      of axolotl serum. Addition of purified bovine hemaglobin in the culture medium
      reduced the serum requirement. Outgrowth from expiants was subcultured by
      transferring groups of cells. Intrinsic markers were used to identify ependymal
      cells in culture. The ependymal cells have characteristic ring-shaped nucleoli in
      both intact axolotl spinal cords and in culture. Indirect immunofluorescence
      examination of intermediate filaments showed that ependymal cells were glial
      fibrillary acidic protein (GFAP) negative and vimentin positive in culture.
      Identification of dividing cells was made using (3)H-thymidine incorporation and
      autoradiography, and by the presence of mitotic figures in the cultured cells.

PMID- 18620323
TI  - X-ray microanalysis of elements present in the matrix of cnidarian nematocysts.
AB  - The composition and concentration of elements, in particular those of metallic
      cations, present in the intracapsular matrix and the wall of nematocysts of
      various cnidarian species have been recorded by means of X-ray microanalysis
      performed on 100nm thick cryosections. The predominant cation detected in the
      nematocyst matrix of the hydrozoan Podocoryne carnea (medusa), the scyphozoan
      Aurelia aurita (scyphopolyp) and the anthozoan Calliactis parasitica (tentacles
      and acontia) is K(+). Mg(2+) prevails in tentacular cysts of Anthopleura
      elegantissima, Actinia equina and Anemonia viridis, whereas, the acrorhagial
      cysts of A. elegantissima and A. equina contain Ca(2+) instead of Mg(2+). The
      acrorhagial cysts of A. viridis contain Mg(2+) like those of the tentacles. In
      the tentacular nematocysts of Podocoryne carnea polyps (Hydrozoa) on the other
      hand ambiguous element contents were found indicating that the cysts of this
      species has no preference for a particular cation. The high values of sulfur
      recorded in the matrix and particularly the wall of all the cysts are reflecting
      the presence of numerous protein disulfide bonds within the structural components
      (wall, shaft, tubule) of the nematocysts.

PMID- 18620324
TI  - The influence of temperature on the fluorine and calcium composition of fish
      scales.
AB  - Proton microprobe studies of the scales of the kahawai (Arripis trutta) and the
      snapper (Chrysophrys auratus) showed non-linear changes in the fluorine to
      calcium ratio that increase with increasing temperature, but both species showed
      a different temperature sensitivity. Fluorine and calcium levels vary within
      years from summer to winter by up to 1000%, making fluorine and calcium levels
      good markers of seasonal events.

PMID- 18620325
TI  - Neural control in the immunocytotoxic destruction of muscles in Diptera.
AB  - Following successful escape from the puparium (eclosion), sets of muscles in all
      three segments of dipteran flies degenerate. Whereas the head and abdominal
      muscles degenerate in response to hormonal triggers released before, and
      immediately after eclosion, the thoracic muscles require a specific neural
      trigger encountered following eclosion. Evidence is presented for the role of
      neural activity in the activation of immunocytes that destroy the thoracic
      muscles. Removal of the neural input by severing the nerve to any particular
      muscle results in survival of the muscle and inactivation of the immunocyte. The
      destruction process can be stopped at any time by severing the nerve and the
      muscle fibres that remain continue to show normal physiology and response to
      stimulation. Elcctrophysiological recordings of the response to lethal attack are
      presented together with ultrastructural evidence demonstrating the invasion of
      muscle fibres by processes of the immunocyte.

PMID- 18620326
TI  - Morphogenesis of the antenna of the male silkmoth, Antheraea polyphemus. II.
      Differential mitoses of 'dark' precursor cells create the Anlagen of sensilla.
AB  - The antenna of the male silkmoth Antheraea polyphemus develops from a one
      layered, flattened epidermal sac during the pupal phase. Within the first day
      post-apolysis (developmental stages 1 and 2), this epithelium differentiates into
      'sensillogenic' and 'nonsensillogenic' regions, while numerous slender 'dark
      cells' interpreted as the precursor cells of sensilla arise in the former.
      Approximately between the first and second day post-apolysis (developmental stage
      3), the dark cells retract to the apical pole of the epidermis, assume a round
      shape, and undergo a series of differential mitoses with spindles usually
      oriented parallel to the epidermal surface. These mitoses finally yield the
      Anlagen of the olfactory sensilla trichodea, each consisting of mostly 6-7 dark
      cells arranged side by side. In most of the Anlagen, 3-4 of these cells are
      situated more basally, each giving off a slender apical process which together
      are arranged in a fascicle. These are the prospective 2-3 sensory neurons plus
      the thecogen cell, which most probably is a sister cell of the former. Three
      additional cells are arranged more apically and partly enclose the fascicle of
      presumed sensory and thecogen cell processes. These are interpreted as the
      trichogen plus 2 tormogen cells, one of the latter degenerating later during
      development. In the basal region of the sensillogenic epidermis, massive signs of
      cell degeneration have been found. At stage 3, the basal epidermal feet in the
      non-sensillogenic regions have assumed a more uniform orientation as compared
      with the preceding stages.

PMID- 18620327
TI  - Morphogenesis of the wing Anlagen in the mealworm beetle tenebrio molitor during
      the last larval instar.
AB  - The wing Anlagen of Tenebrio develop from epidermal cells located on the lateral
      margins of meso- and metathoraces. Three to four days after larval ecdysis, these
      cells start to proliferate slowly, continuing to do so until day 13 which
      corresponds to the period of the pupal commitment of the remaining epidermis. The
      wing Anlagen cells then proliferate rapidly until day 18.5. Three days before
      pupal ecdysis, the mitotic index falls suddenly while 40% of the Anlagen cells
      disappear owing to cell degeneration. The sudden changes observed in the mitotic
      index are correlated with two hemolymphatic peaks in ecdysteroid levels. Anlagen
      of the forewings and hindwings show similar development except for cuticular
      secretion at the end of the instar which is greater on the upper face of the
      forewings. A comparison is made with imaginal discs and histoblasts described in
      other holometabolous insects.

PMID- 18620328
TI  - Innervation of the dorsal body cells of Helix aspersa: Immunocytochemical
      evidence for the presence of FMRF amidelike substances in nerves and synapses.
AB  - In Helix aspersa, single axons or small nerves make synapse-like structures (SLS)
      with dorsal body (DB) cells. The present immunocytochemical study performed on
      the DB-containing connective tissue located around the cerebral commissure
      reveals the presence of FMRFamide-like substances in many nerves of this DB area.
      The immunogold method coupled with electron microscopy show that among the four
      observed axon types, only one, containing 95-110 nm granules, is positive for
      FMRFamide and that most of the SLS between axons and DB cells contain the same
      immunoreactive granule types. The results support the previously suggested role
      of FMRFamide-like peptides in the nervous control of DB cells.

PMID- 18620329
TI  - The persistence of false beliefs.
AB  - Do false beliefs last? To explore this question, this study planted false beliefs
      or memories of a childhood experience with asparagus. We found that these false
      beliefs had consequences for subjects, when assessed directly after the
      suggestive manipulation. Moreover, subjects were brought back two weeks later to
      see if their false beliefs persisted. After two weeks, subjects' confidence in
      their new memories, and the consequences of those memories were diminished, but
      not extinguished. These false beliefs were found to be somewhat weaker than other
      subjects' true beliefs for the same events. Another novel finding was that the
      manipulation was sufficiently powerful to affect actual food choices.

PMID- 18620330
TI  - Natural Plasmodium infections in Brazilian wild monkeys: reservoirs for human
      infections?
AB  - Four hundred and forty-eight samples of total blood from wild monkeys living in
      areas where human autochthonous malaria cases have been reported were screened
      for the presence of Plasmodium using microscopy and PCR analysis. Samples came
      from the following distinct ecological areas of Brazil: Atlantic forest (N=140),
      semideciduous Atlantic forest (N=257) and Cerrado (a savannah-like habitat)
      (N=51). Thick and thin blood smears of each specimen were examined and Plasmodium
      infection was screened by multiplex polymerase chain reaction (multiplex PCR).
      The frequency of Plasmodium infections detected by PCR in Alouatta guariba
      clamitans in the Sao Paulo Atlantic forest was 11.3% or 8/71 (5.6% for Plasmodium
      malariae and 5.6% for Plasmodium vivax) and one specimen was positive for
      Plasmodium falciparum (1.4%); Callithrix sp. (N=30) and Cebus apella (N=39)
      specimens were negative by PCR tests. Microscopy analysis was negative for all
      specimens from the Atlantic forest. The positivity rate for Alouatta caraya from
      semideciduous Atlantic forest was 6.8% (16/235) in the PCR tests (5.5, 0.8 and
      0.4% for P. malariae, P. falciparum and P. vivax, respectively), while C. apella
      specimens were negative. Parasitological examination of the samples using thick
      smears revealed Plasmodium sp. infections in only seven specimens, which had few
      parasites (3.0%). Monkeys from the Cerrado (a savannah-like habitat) (42
      specimens of A. caraya, 5 of Callithrix jacchus and 4 of C. apella) were negative
      in both tests. The parasitological prevalence of P. vivax and P. malariae in wild
      monkeys from Atlantic forest and semideciduous Atlantic forest and the finding of
      a positive result for P. falciparum in Alouatta from both types of forest support
      the hypothesis that monkeys belonging to this genus could be a potential
      reservoir. Furthermore, these findings raise the question of the relationship
      between simian and autochthonous human malaria in extra-Amazonian regions.

PMID- 18620331
TI  - [Effect of polymorphisms on key enzymes in homocysteine metabolism, on plasma
      homocysteine level and on coronary artery-disease risk in a Tunisian population].
AB  - BACKGROUND: Hyperhomocysteinemia is known as an independent-risk factor for
      coronary-artery disease (CAD). However, the effect of homocystein metabolic
      enzymes polymorphisms on CAD is still controversed. We investigated the relation
      between homocystein metabolic key enzymes polymorphisms, homocystenemia and
      coronary stenosis in a Tunisian population. METHODS: Samples were collected from
      251 CAD patients documented by angiography. Genotyping were performed for C677T
      methylene-tetrahydrofolate reductase (MTHFR), A2756G methionine-synthase (MS) and
      844ins 68 cystathionine-beta-synthase (CBS). We measured fasting plasma tHcy,
      folate and vitamin B12. RESULTS: There was significant increase in
      homocysteinemia for homozygous genotypes of C677T MTHFR (p<0.001) and A2756G MS
      (p=0.01), but not for 844ins68 CBS (p=0.105). Potential confounders adjusted odds
      ratios for significant coronary stenosis, associated with MTHFR TT, MS GG and CBS
      insertion, were respectively 1.78 (p=0.041); 2.33 (p=0.036) and 0.87 (p=0.823).
      The effect of mutated MTHFR genotype was more pronounced on homocysteinemia
      (21.4+/-9.1 micromol/L; p<0.001) and coronary stenosis (OR=2.73; p=0.033) at low
      folatemia (< or =6.1 ng/mL). CONCLUSION: MTHFR TT and MS GG genotypes increase
      tHcy concentration and coronary stenosis risk, especially with low folatemia.

PMID- 18620332
TI  - Unilateral testicular tumour associated to congenital adrenal hyperplasia:
      Failure of specific tumoral molecular markers to discriminate between adrenal
      rest and leydigioma.
AB  - Testicular adrenal rest tumours are frequently associated with congenital adrenal
      hyperplasia (CAH). These ACTH-dependent tumours cannot be easily distinguished
      histologically from Leydig-cell tumours. We report the case of a 30-year-old man
      who was explored for infertility, azoospermia and unilateral testicular tumour.
      High levels of 17-OH progesterone and ACTH, low cortisol and undetectable
      gonadotropins levels, associated to bilateral adrenal hyperplasia, led to the
      diagnosis of CAH by 21-OH deficiency with a composite heterozygoty. The
      testicular tumour was first considered as adrenal rest. However, histological
      analysis of this unilateral painful tumour showed a steroid-hormone-secreting
      cell proliferation with atypical and frequent mitosis. To discriminate between a
      benign adrenal rest tumour and a possible malignant leydigioma, tumoral
      expression of specific gene products was analyzed by RT-PCR. No 11-beta
      hydroxylase nor ACTH receptor mRNAs could be found in the tumour, which did not
      behave like usual adrenal rest cells. For this unilateral testicular tumour, the
      lack of adrenal-specific markers associated with a high rate of mitosis and
      pleiomorphism supported a leydigian origin with malignant potential. However,
      lack of tumoral LH-R mRNA expression and a tumour-free 3-year follow-up led us to
      retain the diagnosis of adrenal rest tumour with loss of adrenal gene expression
      and progressive autonomous behaviour.

PMID- 18620333
TI  - Work fatigue and physiological symptoms in different occupations of high
      elevation construction workers.
AB  - The objective of this study is to investigate whether work fatigue and
      physiological symptoms that high-elevation construction workers experience would
      be affected by the occupations. Questionnaires of demographic data and subjective
      fatigue symptoms as well as some physiological measurements were carried out, pre
      and post-shift, on scaffolders, steel fixers, formworkers, electrician-plumbers,
      concreters and miscellaneous workers at a high-rise building construction site.
      This study found that some subjective fatigue symptoms coincide with the life
      style of some workers and that the extent of fatigue symptoms and physiological
      strains varies among different occupations of construction workers. Scaffolders,
      steel fixers and formworkers are categorized as physically demanding fatigue type
      of workers, while concreters, electrician-plumbers and miscellaneous workers as
      general type. The prevalence and occurrence of subjective fatigue symptoms
      indicate high-elevation workers have more complaints of "projection of physical
      impairment" than "drowsiness and dullness" and "difficulty in concentration".
      Some unexpected changes (i.e., post-shift measurements are greater than pre-shift
      ones) in some strength tests in scaffolders and concreters were consistent with
      the observations of how they exercised their bodies during work shift.
      Considerable variation of average heart rate among occupations was found, with
      scaffolders the highest and concreters the lowest. This study concludes that
      questionnaires of subjective fatigue symptoms and some physiological measurements
      can be used as indicators to predict the extent of strains or hazards which
      construction workers encounter. In terms of management program of safety and
      health, more attention should be paid to those physically demanding workers, such
      as scaffolders, workers with lower sense of safety and health, such as
      miscellaneous workers, and workers with older age, such as concreters.

PMID- 18620334
TI  - Classification and mass production technique for three-quarter shoe insoles using
      non-weight-bearing plantar shapes.
AB  - We have developed a technique for the mass production and classification of three
      quarter shoe insoles via a 3D anthropometric measurement of full-size non-weight
      bearing plantar shapes. The plantar shapes of fifty 40-60-year-old adults from
      Taiwan were categorized and, in conjunction with commercially available flat or
      leisure shoe models, three-quarter shoe-insole models were generated using a CAD
      system. Applying a rapid prototype system, these models were then used to provide
      the parameters for manufacturing the shoe insoles. The insoles developed in this
      study have been classified into S, M and L types that offer user-friendly options
      for foot-care providers. We concluded that these insoles can mate tightly with
      the foot arch and disperse the pressure in the heel and forefoot over the foot
      arch. Thus, practically, the pressure difference over the plantar region can be
      minimised, and the user can experience comfort when wearing flat or leisure
      shoes.

PMID- 18620335
TI  - Strength limitations to proper child safety seat installation: implications for
      child safety.
AB  - A majority of child safety restraints are misused in some manner, often leading
      to an increased risk of serious injury or death. It is possible that at least
      some instances of misuse are the result of biomechanical limitations during the
      installation process. Twenty-seven adult participants were trained and then
      monitored in three stages of child safety seat installation. All installations
      were done with an identical restraint system in the rear bench seat of a mocked
      up minivan. EMG of 10 muscles, as well as trunk, shoulder, and wrist postures
      were analyzed. Peak maximum efforts were often required of the trunk extensor,
      forearm, and anterior shoulder muscles during the installation process. Routing
      and tightening of the seatbelt, as well as placing and securing the child into
      the seat were observed to be particularly difficult tasks. Many portions of the
      child safety seat installation process were found to be very physically
      demanding; some individuals may not be capable of performing these tasks
      correctly, thereby putting the child at greater risk in the motor vehicle.

PMID- 18620336
TI  - The dual-state theory of prefrontal cortex dopamine function with relevance to
      catechol-o-methyltransferase genotypes and schizophrenia.
AB  - There is now general consensus that at least some of the cognitive deficits in
      schizophrenia are related to dysfunctions in the prefrontal cortex (PFC) dopamine
      (DA) system. At the cellular and synaptic level, the effects of DA in PFC via D1-
      and D2-class receptors are highly complex, often apparently opposing, and hence
      difficult to understand with regard to their functional implications.
      Biophysically realistic computational models have provided valuable insights into
      how the effects of DA on PFC neurons and synaptic currents as measured in vitro
      link up to the neural network and cognitive levels. They suggest the existence of
      two discrete dynamical regimes, a D1-dominated state characterized by a high
      energy barrier among different network patterns that favors robust online
      maintenance of information and a D2-dominated state characterized by a low energy
      barrier that is beneficial for flexible and fast switching among representational
      states. These predictions are consistent with a variety of electrophysiological,
      neuroimaging, and behavioral results in humans and nonhuman species. Moreover,
      these biophysically based models predict that imbalanced D1:D2 receptor
      activation causing extremely low or extremely high energy barriers among activity
      states could lead to the emergence of cognitive, positive, and negative symptoms
      observed in schizophrenia. Thus, combined experimental and computational
      approaches hold the promise of allowing a detailed mechanistic understanding of
      how DA alters information processing in normal and pathological conditions,
      thereby potentially providing new routes for the development of pharmacological
      treatments for schizophrenia.

PMID- 18620337
TI  - Abnormal corpus callosum integrity in bipolar disorder: a diffusion tensor
      imaging study.
AB  - OBJECTIVE: Abnormalities in the anterior interhemispheric connections provided by
      the corpus callosum (CC) have long been implicated in bipolar disorder (BD). In
      this study, we used complementary diffusion tensor imaging methods to study the
      structural integrity of the CC and localization of potential abnormalities in BD.
      METHODS: Subjects included 33 participants with BD and 40 healthy comparison
      participants. Fractional anisotropy (FA) measures were compared between groups
      with region of interest (ROI) methods to investigate the anterior, middle, and
      posterior CC and voxel-based methods to further localize abnormalities. RESULTS:
      In ROI-based analyses, FA was significantly decreased in the anterior and middle
      CC in the BD group (p < .05). Voxel-based analyses similarly localized group
      differences to the genu, rostral body, and anterior midbody of CC (p < .05,
      corrected). CONCLUSION: The findings demonstrate abnormalities in the structural
      integrity of the anterior CC in BD that might contribute to altered
      interhemispheric connectivity in this disorder.

PMID- 18620338
TI  - Cortisol diurnal rhythm and stress reactivity in male adolescents with early
      onset or adolescence-onset conduct disorder.
AB  - BACKGROUND: Previous studies have reported lower basal cortisol levels and
      reduced cortisol responses to stress in children and adolescents with conduct
      disorder (CD). It is not known whether these findings are specific to early-onset
      CD. This study investigated basal and stress-induced cortisol secretion in male
      participants with early-onset and adolescence-onset forms of CD. METHODS: Forty
      two participants with early-onset CD, 28 with adolescence-onset CD, and 95
      control subjects participated in the study. They collected saliva across the day
      to assess their cortisol awakening response and diurnal rhythm. Subsequently,
      salivary cortisol was measured before, during, and after a psychosocial stress
      procedure designed to elicit frustration. Cardiovascular activity and subjective
      mood states were also assessed during stress exposure. RESULTS: There were no
      group differences in morning cortisol levels or the size of the cortisol
      awakening response. Basal cortisol levels in the evening and at 11 am during the
      laboratory visit were higher in both CD subgroups relative to control subjects.
      In contrast, cortisol and cardiovascular responses to psychosocial stress were
      reduced in both CD subgroups compared with control subjects. All groups reported
      similar increases in negative mood states during stress. CONCLUSIONS: Our
      findings suggest that group differences in cortisol secretion are most pronounced
      during stress exposure, when participants with CD show cortisol hyporeactivity
      compared with control subjects. There was no evidence for reduced basal cortisol
      secretion in participants with CD, but rather increased secretion at specific
      time points. The results do not support developmentally sensitive differences in
      cortisol secretion between CD subtypes.

PMID- 18620340
TI  - Phox2b expression in the aldosterone-sensitive HSD2 neurons of the NTS.
AB  - The transcription factor Phox2b is necessary for the development of the nucleus
      of the solitary tract (NTS). In this brainstem nucleus, Phox2b is expressed
      exclusively within a subpopulation of glutamatergic neurons. The present
      experiments in the adult rat were designed to test whether this subpopulation
      includes the aldosterone-sensitive NTS neurons, which express the enzyme 11-beta
      hydroxysteroid dehydrogenase type 2 (HSD2). Nuclear Phox2b was found in virtually
      all the HSD2 neurons (95-99%, n = 6 cases). Unlike the activity-related
      transcription factor c-Fos, Phox2b expression in the HSD2 neurons was not
      influenced by dietary sodium deprivation. The ubiquitous expression of Phox2b by
      the HSD2 neurons suggests that they are developmentally related to other Phox2b
      dependent neurons of the NTS and that they release the excitatory
      neurotransmitter glutamate. This finding also suggests that human Phox2b
      mutations, which cause the central congenital hypoventilation syndrome (CCHS,
      also known as Ondine's curse), may also produce deficits in central aldosterone
      signaling and appetitive or autonomic responses to sodium deficiency.

PMID- 18620339
TI  - Cytokine mRNA induction by interleukin-1beta or tumor necrosis factor alpha in
      vitro and in vivo.
AB  - Hypothalamic and cortical mRNA levels for cytokines such as interleukin-1beta
      (IL1beta), tumor necrosis factor alpha (TNFalpha), nerve growth factor (NGF) and
      brain derived neurotrophic factor (BDNF) are impacted by systemic treatments of
      IL1beta and TNFalpha. To investigate the time course of the effects of IL1beta
      and TNFalpha on hypothalamic and cortical cytokine gene expression, we measured
      mRNA levels for IL1beta, TNFalpha, interleukin-6 (IL-6), interleukin-10 (IL-10),
      IL1 receptor 1, BDNF, NGF, and glutamate decarboxylase-67 in vitro using
      hypothalamic and cortical primary cultures. IL1beta and TNFalpha mRNA levels
      increased significantly in a dose-dependent fashion after exposure to either
      IL1beta or TNFalpha. IL1beta increased IL1beta mRNA in both the hypothalamic and
      cortical cultures after 2-6 h while TNFalpha mRNA increased significantly within
      30 min and continued to rise up to 2-6 h. Most of the other mRNAs showed
      significant changes independent of dose in vitro. In vivo,
      intracerebroventricular (icv) injection of IL1beta or TNFalpha also significantly
      increased IL1beta, TNFalpha and IL6 mRNA levels in the hypothalamus and cortex.
      IL1beta icv, but not TNFalpha, increased NGF mRNA levels in both these areas.
      Results support the hypothesis that centrally active doses of IL1beta and
      TNFalpha enhance their own mRNA levels as well as affect mRNA levels for other
      neuronal growth factors.

PMID- 18620341
TI  - Modeling the top-down influences on the lateral interactions in the visual
      cortex.
AB  - Attention modulates the amount of excitatory and inhibitory lateral interactions
      in the visual cortex. A recurrent neural network is proposed to account for
      modulatory influence of top-down signals. In the model, two types of inhibitions
      are distinguished: dendritic and lateral inhibitions. Dendritic inhibition
      regulates the amount of impact that surrounding cells may exert on a target cell
      via the dendrites of excitatory neurons and the dendrites of subpopulation of
      inhibitory neurons mediating lateral inhibition. Attention increases the amount
      of dendritic inhibition and prevents contextual interactions, while it has no
      effect on the target cell when there is no surround input. Computer simulations
      showed that the proposed model is able to exhibit properties of attentional
      gating. In the condition of focused attention, neural activity in the presence of
      surrounding stimuli is restored to the level as when the target stimulus is
      presented alone. Moreover, the model is able to show contrast gain and response
      gain on the contrast sensitivity function depending on the strength of the
      dendritic inhibition.

PMID- 18620342
TI  - Multisensory temporal numerosity judgment.
AB  - In temporal numerosity judgment, observers systematically underestimate the
      number of pulses. The strongest underestimations occur when stimuli are presented
      with a short interstimulus interval (ISI) and are stronger for vision than for
      audition and touch. We investigated if multisensory presentation leads to a
      reduction of underestimation. Participants were presented with 2 to 10
      (combinations of) auditory beeps, tactile taps to the index finger and visual
      flashes at different ISIs (20 to 320 ms). For all presentation modes, we found
      underestimation, except for small number of pulses. A control experiment showed
      that the latter is due to a (cognitive) range effect. Averaged over conditions,
      the order of performance of sensory modalities is touch, audition and last
      vision. Generally, multisensory presentation improves performance over the
      unisensory presentations. For larger ISIs (160 and 320 ms), we found a tendency
      toward a reduction in variance for the multisensory presentation modes. For
      smaller ISIs (20 and 40 ms), we found a reduction in underestimation, but an
      increase in variance for the multisensory presentation modes. In the discussion,
      we relate these two findings to Maximum Likelihood Estimation (MLE) models
      predicting that multisensory integration reduces variance.

PMID- 18620343
TI  - Seeing the hand boosts feeling on the cheek.
AB  - Tactile acuity improves when subjects look at the stimulated body part, even when
      vision does not provide any information relevant to touch. This "visual
      enhancement of touch" (VET), might involve modulation of primary somatosensory
      cortex (SI) processing by multimodal information related to the body. SI shows a
      characteristic somatotopic organization, with the face and hand represented
      laterally and adjacent to each other, and the foot represented more medially. The
      aim of this study was to investigate whether VET is limited to the viewed body
      part, spreads to all body parts, or generalizes only to body parts represented in
      SI closely to the viewed body part. Tactile acuity was assessed in healthy
      subjects on the hand, face and foot, while subjects viewed either their
      stimulated hand, their foot or were blindfolded: viewing the hand, compared to
      blindfold condition, enhanced tactile sensitivity on the hand and also on the
      face, but not on the foot. Conversely, viewing the foot, compared to blindfold
      condition, improved touch only on the foot. Two control experiments assured this
      effect was due to viewing the body and not to directing visuo-spatial attention
      toward the location of tactile stimulation. The present results show that VET
      acts accordingly to a somatotopic gradient based on SI organization, suggesting
      that this multisensory effect may occur within SI. This finding might have a
      possible application to facilitate the recovery of tactile deficits in patients
      with a lesion of somatosensory cortices.

PMID- 18620344
TI  - Right lateral position does not affect gastric transit times of video capsule
      endoscopy: a prospective study.
AB  - BACKGROUND: Video capsule endoscopy (VCE) examination of the small bowel is not
      complete in approximately 20% of the procedures. This fact limits its diagnostic
      yield. One of the main factors that influences the small-bowel transit time
      (SBTT) is the gastric transit time (GTT), ie, the interval in which the capsule
      stays in the stomach. It has been described that placing the patient in a right
      lateral position (RLP) after swallowing the capsule could decrease the GTT.
      OBJECTIVE: To investigate whether the RLP, after the patient swallows the
      capsule, shortens the GTT and, secondarily, increases the rate of complete
      procedures. DESIGN: Randomized prospective study. SETTING: Third-level hospital.
      PATIENTS: Consecutive outpatients in whom VCE was indicated. Exclusion criteria
      were inpatients and previous gastric surgery. INTERVENTION: GTT for RLP 30
      minutes after swallowing the capsule versus non-RLP (standing up position). MAIN
      OUTCOME MEASUREMENTS: The GTT, SBTT, and rate of complete procedures (examination
      of the entire small bowel). RESULTS: We did not observe significant differences
      in the GTT, the SBTT, and the complete procedures between groups. LIMITATION:
      Only outpatients were included. CONCLUSIONS: RLP after swallowing the capsule
      does not influence either GTT nor the rate of VCE complete procedures.

PMID- 18620345
TI  - Comparison of EMR and endoscopic submucosal dissection for en bloc resection of
      early esophageal cancers in Japan.
AB  - BACKGROUND: EMR and endoscopic submucosal dissection (ESD) are now being
      increasingly used for the treatment of esophageal cancers. However, their
      efficacies in smaller lesions have not been compared. OBJECTIVE: For effective
      use of these methods, we compared the results of ESD and 2 major EMR methods for
      treating esophageal cancers of <or=20 mm. DESIGN: A retrospective study. SETTING:
      A cancer-referral center. PATIENTS: A total of 136 patients with 171 lesions
      <or=20 mm who presented between January 2002 and October 2007 were enrolled. MAIN
      OUTCOME MEASUREMENTS: En bloc and curative resection. RESULTS: Of the 171
      lesions, 168 were squamous-cell carcinoma and 3 were adenocarcinoma. The en bloc
      resection rates decreased in the order of ESD (100%), EMR using a transparent cap
      (EMRC) (87%), and 2-channel EMR (71%). However, the differences showed only
      marginal significance. The curative resection rate of ESD (97%) was significantly
      higher than those of the other 2 methods. Furthermore, the curative resection
      rate of EMRC (71%) was significantly higher than that of 2-channel EMR (46%). In
      lesions <15 mm, the en bloc and curative resection rates were significantly
      higher for EMRC (100% and 86%, respectively) than 2-channel EMR (86% and 51%,
      respectively), whereas no significant differences were found between the en bloc
      and curative resection rates of EMRC and ESD. There were no differences in the
      complication rates. LIMITATIONS: A single-center, retrospective analysis.
      CONCLUSIONS: ESD was found to be the best endoscopic resection method, even for
      smaller esophageal cancers. EMRC would be a good alternative to ESD for lesions
      <15 mm.

PMID- 18620346
TI  - Clinical manifestations and management of buried bumper syndrome in patients with
      percutaneous endoscopic gastrostomy.
AB  - BACKGROUND: Buried bumper syndrome has been regarded as an uncommon and late
      complication after percutaneous endoscopic gastrostomy (PEG) tube insertion. A
      variety of techniques have been reported to treat this problem, but only a few
      published cases exist. OBJECTIVE: Our purpose was to present the clinical
      manifestations and our management of a series of 19 patients with buried bumper
      syndrome. DESIGN: Case series study. SETTING: Referral medical centers. PATIENTS:
      Within 5 years, 31 episodes of buried bumper syndrome occurred in 10 men and 9
      women. The estimated prevalence was 8.8% (19 in 216 PEG procedures during this
      period). INTERVENTION: All the buried tubes were removed smoothly by external
      traction and replaced with a new pull-type feeding tube by the pull method or a
      button or balloon replacement tube after dilation of the old tract. MAIN OUTCOME
      MEASUREMENTS: Success rate, complication rate. RESULTS: The duration between
      occurrence of buried bumper syndrome and PEG placement ranged from 1 to 50
      months, with a median of 18 months. All the episodes were treated successfully
      except for one, in which reinsertion failed and a new PEG tube was inserted 1
      week later. No significant complications occurred. LIMITATION: Small sample size.
      CONCLUSIONS: Buried bumper syndrome is not that uncommon and can occur soon after
      insertion of a PEG tube. The buried tube can be safely removed by external
      traction and in most cases can then be replaced with a pull-type or balloon
      replacement tube.

PMID- 18620347
TI  - The "cecal patch" in patients with ulcerative colitis.

PMID- 18620348
TI  - Creation of an effective and reproducible nonsurvival porcine model that
      simulates actively bleeding peptic ulcers.
AB  - BACKGROUND: Efforts to develop improved endoscopic therapeutic methods for upper
      GI bleeding require an effective animal model. OBJECTIVE: To develop a
      nonsurvival porcine model that simulates acute peptic ulcer bleeding. DESIGN:
      Prospective animal (porcine) study. SETTING: Animal laboratory. INTERVENTIONS: A
      surgical seromyotomy was created along the external surface of the greater
      curvature of the stomach in anesthesized pigs. A submucosal plane was developed
      and the gastroepiploic bundle, in continuity, was placed adjacent to the mucosa,
      and the seromuscular tissues were re-approximated over the vascular bundle. By
      using EGD, a needle-knife with electrocautery was then used to incise the mucosal
      tissue overlying the vascular bundle. Standard endoscopic methods for bleeding
      control were then tested in this animal model. MAIN OUTCOME MEASUREMENTS: To
      evaluate whether successful bleeding that simulates submucosal arterial bleeding
      from peptic ulcer disease could be achieved in a porcine animal model. RESULTS:
      Successful simulation of active peptic ulcer bleeding was achieved with this
      nonsurvival porcine model in a total of 5 sequential pigs. Other porcine models
      for bleeding were tested and found to be unsatisfactory. Hemoclips and
      combination injection-thermal therapy were used to stop bleeding over Doppler
      positive areas, with subsequent endoscopic nonimaging Doppler US probe
      examination of the ulcer bed revealing a negative Doppler signal. LIMITATIONS:
      This was an animal laboratory study. Further human studies would be ideal once
      any future endoscopic interventions are proven to be safe in animals.
      CONCLUSIONS: This active bleeding ulcer model can be used to develop future
      endoscopic therapies and for training purposes.

PMID- 18620349
TI  - Acute abdomen: superior mesenteric artery occlusion.

PMID- 18620352
TI  - Intuitive robust stability metric for PID control of self-regulating processes.
AB  - Published methods establish how plant-model mismatch in the process gain and dead
      time impacts closed-loop stability. However, these methods assume no plant-model
      mismatch in the process time constant. The work presented here proposes the
      robust stability factor metric, RSF, to examine the effect of plant-model
      mismatch in the process gain, dead time, and time constant. The RSF is presented
      in two forms: an equation form and a visual form displayed on robustness plots
      derived from the Bode and Nyquist stability criteria. This understanding of
      robust stability is reinforced through visual examples of how closed-loop
      performance changes with various levels of plant-model mismatch. One example
      shows how plant-model mismatch in the time constant can impact closed-loop
      stability as much as plant-model mismatch in the gain and/or dead time.
      Theoretical discussion shows that the impact is greater for small dead time to
      time constant ratios. As the closed-loop time constant used in Internal Model
      Control (IMC) tuning decreases, the impact becomes significant for a larger range
      of dead time to time constant ratios. To complete the presentation, the RSF is
      used to compare the robust stability of IMC-PI tuning to other PI, PID, and PID
      with Filter tuning correlations.

PMID- 18620351
TI  - The effect of hormone therapy on olfactory sensitivity is dependent on
      apolipoprotein E genotype.
AB  - Patients with Alzheimer's disease (AD) show a deficit in olfactory threshold
      sensitivity. The Apolipoprotein E (ApoE) epsilon4 allele is associated with
      increased risk of AD and earlier symptom onset. Hormone therapy (HT) may exert
      neuroprotective effects on brain areas affected by AD. The current study
      investigated the effect of HT on performance on an olfactory threshold test in
      epsilon4 positive and epsilon4 negative non-hysterectomized, non-demented,
      elderly females and AD patients. Among the non-demented participants, epsilon4
      positive females who had received HT performed 1) significantly better than those
      without HT, and 2) at levels similar to those of epsilon4 negative females. In
      contrast, those without HT who were epsilon4 positive performed significantly
      worse than those who were epsilon4 negative. HT had no effect on performance in
      AD patients regardless of epsilon4 status. These results suggest that HT may
      offer protection against loss of olfactory function in epsilon4 positive
      individuals in preclinical stages of AD. Future research is warranted in order to
      investigate further the neuroprotective role of HT on sensory and cognitive
      functions in non-demented aging individuals.

PMID- 18620354
TI  - Comments on "Ballistics: a primer for the surgeon".

PMID- 18620353
TI  - Laparotomy and unstable pelvic fractures.
AB  - The requirement for laparotomy was analysed in 91 patients with unstable pelvic
      fractures. Laparotomies were classified as positive or negative. Injuries found
      at laparotomy were compared with the pelvic fracture pattern. Laparotomy was
      carried out in 28 patients but was unnecessary in 8. Eleven of the 28 patients
      died, a mortality of 39%. Vertical shear and combined mechanical injury pelvic
      fracture patterns had the highest incidence of abdominal injuries (28%) but the
      fracture pattern was not a reliable guide to the presence or nature of intra
      abdominal injury. Inadequate preoperative investigations contributed to the eight
      negative laparotomies and three of these patients died. Laparotomy was only
      necessary in 22% of our patients. Major pelvic fractures with concomitant intra
      abdominal injuries have a high mortality rate. Preoperative CT scanning was 98%
      accurate in the identification of intra-abdominal injury and was the most useful
      investigation for determining the need for laparotomy and minimising the risk of
      negative laparotomy.

PMID- 18620355
TI  - Nonobstetric lower genital tract injuries in rural India.
AB  - OBJECTIVE: To study the impact of nonobstetric genital tract injury (NOGTI) in
      rural India. METHODS: A prospective observational study of 52 consecutive women
      admitted with NOGTIs caused by voluntary coitus or accidental injury. Details of
      the causes of trauma, clinical presentations, and management were recorded.
      RESULTS: A total of 17 women (32.7%) presented with coital trauma, while 35 women
      (67.3%) sustained noncoital injuries: bicycle/automobile accidents (10); fall
      from height (7); cattle horn injury (7); straddle-type trauma (6); leech bites
      (3); and vaginal foreign bodies (2). Most women had multiple injuries; 15 women
      developed vulvar hematomas and 3 had anorectal lacerations. Management included
      immediate resuscitation along with primary repair of injuries, evacuation of
      vulvar hematomas, and removal of vaginal foreign bodies. Fifteen women (28.8%)
      required blood transfusions; none of the women died. CONCLUSIONS: Severe
      hemorrhage caused by NOGTIs is potentially fatal in rural settings if treatment
      is delayed. Prompt resuscitation, early referral, and appropriate surgical
      intervention can avert both morbidity and mortality.

PMID- 18620356
TI  - Maternal obesity and neonatal congenital cardiovascular defects.
AB  - OBJECTIVE: To determine whether isolated congenital heart defects (CHDs) were
      associated with maternal obesity. METHOD: In a retrospective study we compared
      the incidence and severity of isolated CHDs in the offspring of 428 women divided
      into 3 groups, one of women of normal weight (n=141), one of obese women (n=228),
      and one of morbidly obese women (n=59) according to their body mass index.
      RESULTS: There were 143 mild (66.8%), 44 moderate (20.6%), and 27 complex (12.6%)
      forms of CHDs in the offspring and septal defects were the most common (61.7%).
      No significant differences were found among the 3 groups of women regarding the
      type or severity of CHDs in their respective offspring, or the corrective cardiac
      surgery required. CONCLUSION: No association was found between maternal weight
      and isolated CHDs in the offspring.

PMID- 18620357
TI  - Overexpression of heme oxygenase-1 in coronary atherosclerosis of Japanese
      autopsies with diabetes mellitus: Hisayama study.
AB  - Few studies regarding the topographical expression of heme oxygenase-1 (HO-1) and
      its pathophysiological role in human coronary atherosclerotic lesions,
      particularly in relation to type 2 diabetes mellitus (DM) and intimal
      angiogenesis, have been reported. HO-1 expression was immunohistochemically
      examined in 312 tissue blocks of coronary arteries obtained from 53 Japanese
      autopsy cases in Hisayama cohort study that included 19 diabetic subjects and 34
      age- and sex-matched non-diabetic subjects (56-93 years old, mean+/-S.D.: 73+/
      10). The HO-1 was ubiquitously distributed in atherosclerotic intima, and was
      mainly expressed by macrophages and endothelial cells, and partly by smooth
      muscle cells. The prevalence of HO-1 expression increased as the lesion type (as
      classified by the American Heart Association (AHA) Committee) and stenotic grade
      progressed (p<0.0001), and was significantly higher in diabetic than in non
      diabetic subjects (p<0.01). This HO-1 overexpression was associated with greater
      CD-68-positive macrophage infiltration (p=0.005). Interestingly, the distribution
      of HO-1-positive cells was accentuated in coronary atherosclerotic lesions with
      intimal microvessels in diabetic subjects (p<0.05), particularly those with
      hypercholesterolemia (p<0.05), and was preferentially distributed in the shoulder
      region of atherosclerotic lesion type IV in the AHA classification (p<0.01). In
      conclusion, HO-1 expression was distributed in overall human coronary
      atherosclerotic lesions, particularly in diabetic subjects, indicating that HO-1
      expression is intimately associated with atherogenesis and may play an important
      role as an adaptive molecule in the inflammatory-repair process. The association
      of HO-1 overexpression with a greater extent of intraplaque angiogenesis suggests
      a multi-faceted role for HO-1 in modulating the progression of atherosclerosis.

PMID- 18620358
TI  - Use of cyclohexanedimethanol as a nonflammable organic solvent for industrial
      scale reversed phase chromatography.
AB  - This work demonstrates that cyclohexanedimethanol is an effective nonflammable
      organic solvent for the pilot scale reversed phase chromatography of recombinant
      apolipoprotein A-I(Milano). Cyclohexanedimethanol has low viscosity in water,
      enabling the use of conventional low pressure process scale chromatography
      columns and hardware. Results from pilot scale manufacturing using a 30 cm
      diameter CG71M packed column indicate that a 5.7 log reduction in E. coli host
      cell protein with >80% yield can be obtained for the purification of
      apolipoprotein A-I(Milano).

PMID- 18620359
TI  - Quantification of polycyclic aromatic hydrocarbons based on comprehensive two
      dimensional gas chromatography-isotope dilution mass spectrometry.
AB  - Comprehensive two-dimensional gas chromatography (GCxGC) offers favourable
      resolution and sensitivity compared with conventional one-dimensional gas
      chromatography (1D-GC), as reported in many studies. These characteristics are of
      major interest when analytes are in trace concentration, and are present in
      complex mixtures, as is the case of polycyclic aromatic hydrocarbons (PAHs) in
      atmospheric particulate samples. Whilst GCxGC has been widely applied to
      identification of different types of analytes in several matrices, less seldom
      has it been used for quantification of these analytes. Although several
      quantitative methods have been proposed, they may be tedious and/or require
      considerable user development. Whereas quantification in 1D-GC is a routine and
      well-established procedure, in GCxGC, it is not so straightforward, especially
      where novel or untested procedures have yet to be incorporated into software
      packages. In the present study, it is proposed that a subset of the modulated
      peaks generated for each solute may be summed, based on the specific target ion
      mass of each compound present in a certified standard reference material (SRM)
      1649a (urban dust). The ratio between a PAH and its corresponding deuterated (PAH
      d) form showed that there is no statistical loss of sensitivity when this ratio
      is calculated based on whether the total sum of modulated peaks, or if only the
      two or the three most intense modulated peaks, are employed. Manual integration
      may be required, and here was found to give more acceptable values than automatic
      integration. Automated integration has been shown here to underestimate the
      modulated peak responses when low concentrations of PAHs were analyzed. Although
      for most PAHs good agreement with the certified values were observed, the
      analytical method needs to be further optimized for some of the other PAH, as can
      be see with those PAH with high variability in the range of urban dust analyzed.

PMID- 18620360
TI  - Determination of phenolic compounds and hydroxymethylfurfural in meads using high
      performance liquid chromatography with coulometric-array and UV detection.
AB  - The objective of this study was the determination of 25 phenolic compounds in
      different mead samples (honeywines) using high performance liquid chromatography
      (HPLC) with coulometric-array detection and in case of hydroxymethylfurfural with
      UV detection. Our method was optimized in respect to both the separation
      selectivity of individual phenolic compounds and the maximum sensitivity with the
      electrochemical detection. The method development included the optimization of
      mobile phase composition, the pH value, conditions of the gradient elution and
      the flow rate using a window-diagram approach. The developed method was used for
      the determination of limits of detection and limits of quantitation for
      individual compounds. The linearity of calibration curves, accuracy and precision
      (intra- and inter-day) at three concentration levels (low, middle and high
      concentration range) were verified. Mead samples were diluted with the mobile
      phase at 1:1 to 1:50 ratio depending on the concentration and filtered through a
      PTFE filter without any other sample pre-treatment. Phenolic compounds
      concentration was determined in 50 real samples of meads and correlated with
      meads composition and hydroxymethylfurfural concentration. The most frequently
      occurred compounds were protocatechuic acid and vanillic acid (both of them were
      present in 98% samples), the least occurred compounds were (+)-catechin (10%
      samples) and sinapic acid (12% samples). Vanillin and ethylvanillin, which are
      used as artificial additives for the taste improvement, were found in 60% and 42%
      samples, respectively. Hydroxymethylfurfural concentration, as an indicator of
      honey quality, was in the range from 2.47 to 158 mg/L. Our method is applicable
      for the determination of 25 phenolic compounds in mead, honey and related natural
      samples.

PMID- 18620361
TI  - Synthesis of Pd particle-deposited microporous silica membranes via a vacuum
      impregnation method and their gas permeation behavior.
AB  - Pd particle-deposited microporous silica membranes were synthesized to improve
      hydrogen permselectivity of the microporous silica membrane and to overcome high
      cost of palladium and crack formation through hydrogen embrittlement. Pd
      particles below 400 nm in diameter were readily deposited on the microporous
      silica membrane via a vacuum-impregnation method by using a
      Pd(C(3)H(5))(C(5)H(5)) precursor. After deposition of Pd particles on the
      microporous silica membrane, hydrogen permselectivity over nitrogen considerably
      increased from 11-28 to 30-115 in a permeation temperature range of 25-350
      degrees C due to plugging membrane defects and hydrogen adsorption diffusion
      through the interface between the Pd and silica layer. The activation energy of
      the Pd-deposited silica membrane (6.32 kJ mol(-1)) was higher than that of the
      microporous silica membrane (4.22 kJ mol(-1)). In addition, the Pd-particle
      deposition led to an increase in the permselectivity of He and CO(2) with little
      chemical affinity for the Pd particles, which indicates that Pd-particle
      deposition gives the effect of plugging defects such as pinholes or cracks, which
      could be formed during the membrane preparation. Therefore it is demonstrated
      that Pd-particle deposition on the silica membrane is effective for induction of
      the hydrogen adsorption diffusion and plugging membrane defects.

PMID- 18620362
TI  - Organic inorganic dye filler for polymer: blue-coloured layered double hydroxides
      into polystyrene.
AB  - A series of blue dye molecules, Evans blue (EB), Chicago sky blue (CB), Niagara
      blue (NB) were incorporated by direct co-precipitation within the galleries of
      negatively charge layered double hydroxide (LDH). The materials of cation
      composition Zn/Al = 2 lead to well-defined organic inorganic assemblies. The
      molecular arrangement of the interleaved dye molecule is proposed by 1D
      electronic density projection along the stacking direction for the hydrothermally
      treated samples with alternatively a highly inclined orientation of EB and CB and
      a parallel-bilayer arrangement for NB. Blue coloured LDH assemblies were
      subsequently dispersed into polystyrene (PS). It was found that the hybrid
      fillers do not interfere in the radical polymerization of styrene, giving rise to
      similar molecular weight and polydispersity than filler free PS, while higher
      glass transition temperatures were obtained for the nanocomposites. This was
      consistent with the rheological behaviour with the observation for LDH/NB filler
      based nanocomposite of shear thinning exponent different from zero, underlining
      frictional interaction between filler and PS chain. The absorption maximum
      slightly blue-shifted for the hybrid filler in comparison to the corresponding
      organic dye was found unmodified for the PS nanocomposite, thus giving rise to
      blue coloured plastic films, reminiscent somehow of the blue Maya effect.

PMID- 18620363
TI  - Introduction: molecular and biomolecular electrochemistry.

PMID- 18620364
TI  - One-electron and two-electron transfers in electrochemistry and homogeneous
      solution reactions.

PMID- 18620365
TI  - Electrochemical approach to the mechanistic study of proton-coupled electron
      transfer.

PMID- 18620367
TI  - Molecular catalysis of electrochemical reactions. Mechanistic aspects.

PMID- 18620366
TI  - Electron transfer initiated reactions: bond formation and bond dissociation.

PMID- 18620368
TI  - Direct electrochemistry of redox enzymes as a tool for mechanistic studies.

PMID- 18620370
TI  - Electrochemical monitoring of single cell secretion: vesicular exocytosis and
      oxidative stress.

PMID- 18620369
TI  - Enzymes as working or inspirational electrocatalysts for fuel cells and
      electrolysis.

PMID- 18620371
TI  - Electron transfer through molecules and assemblies at electrode surfaces.

PMID- 18620372
TI  - Single-molecule electron transfer in electrochemical environments.

PMID- 18620373
TI  - Clustering dynamics of the metal-benzene sandwich complex: the role of
      microscopic structure of the solute in the bis(eta6-benzene)chromium .Arn
      Clusters (n = 1-15).
AB  - Ar clustering dynamics around the metal-benzene sandwich complex, bis(eta (6)
      benzene)chromium: Cr(Bz) 2, is found to occur in two distinct regimes. The shift
      of the ionization potential (IP) upon the addition of Ar is measured to be 151 cm
      (-1), and it is constant until the number of Ar solvents ( n) becomes 6. The IP
      shift per Ar is found to be suddenly decreased to 82 cm (-1) for the clusters of
      n = 7-12. The cluster distribution indicates that the n = 6 cluster is most
      populated in the molecular beam. These experimental findings with the aid of ab
      initio calculation indicate that the first six Ar solvent molecules are attached
      to top and bottom of Cr(Bz) 2 to give the robust structure for the Cr(Bz) 2-Ar 6
      cluster whereas the next six Ar molecules are gathered on the side of the solute
      core to give the highly symmetric structure of the Cr(Bz) 2-Ar 12 cluster.

PMID- 18620374
TI  - Evidence for Rydberg doorway states in photoion pair formation in bromomethane.
AB  - The vacuum ultraviolet laser-excited photoion-pair formation spectrum of CH 3Br
      has been measured under high resolution in the threshold region. The (2 + 1) and
      (3 + 1) resonance-enhanced multiphoton ionization spectra in the same energy
      region are also reported. By comparison of the spectra in this and a more
      extended region, resonances in the photoion-pair formation spectrum are assigned
      to p and f Rydberg states. It is concluded that all the structure in the photoion
      pair formation spectrum near threshold can be accounted for by members of the
      Omega = 0 subset of Rydberg states that act as doorway states to the ion channel.

PMID- 18620376
TI  - Vibrational relaxation of highly vibrationally excited O3 in collisions with OH.
AB  - We report a theoretical study of highly excited O3 in collisions with
      vibrationally cold OH. Special emphasis is placed on initial vibrational energies
      of O3 between 9 and 21 kcal mol(-1). All calculations have employed the
      quasiclassical trajectory method and the realistic double many-body expansion
      potential energy surface for HO 4((2)A). Many aspects of the title relaxation
      process are presented. The results indicate that it may not be ignorable in
      studying the stratospheric ozone budget.

PMID- 18620377
TI  - Intramolecular excimer formation and photoinduced electron-transfer process in
      bis-1,8-naphthalimide dyads depending on the linker length.
AB  - The photophysical properties of bis-1,8-naphthalimide (NI-L-NI) dyads with
      different linkers ( L = -C 3H 6-, -C 4H 8-, -C 6H 12-, -C 8H 16-, and -C 9H 18-)
      as well as the reference NI derivative (NI-C 7H 15) were investigated in CH 3CN
      and H 2O/CH 3CN (v/v = 1:9). The normal fluorescence peak of (1)NI*-L-NI was
      observed at 379 nm together with a broad emission at longer wavelength both in
      aprotic CH 3CN and in H 2O/CH 3CN, which is assigned to an excimer, (1)(NI-L
      NI)*. The excimer emission maximum was blue-shifted with increasing length of the
      linker. The photoinduced electron-transfer process of NI-L-NI was also
      investigated in both solvents by using nanosecond-laser flash photolysis. The T 1
      T n absorption band for (3)NI*-L-NI was observed around 470 nm in both solvents.
      In H 2O/CH 3CN, NI-L-NI is solvated with H 2O in the ground state to exist as
      solvated NI-L-NI. In the excited triplet state, the NI radical anion (NI (*-))
      was generated via the intramolecular quenching of (3)NI*-L-NI by another NI
      moiety. The solvated NI (*-)-L-NI may undergo the proton abstraction process to
      give NI(H) (*)-L-NI, which can be confirmed by the transient absorption band at
      410 nm. This band was not observed in pure aprotic CH 3CN.

PMID- 18620378
TI  - A VB/MM view of the identity S(N)2 valence-bond state correlation diagram in
      aqueous solution.
AB  - The valence-bond state correlation diagram (VBSCD), which was developed by Shaik
      and co-workers is an excellent tool to understand reactivity patterns in chemical
      reactions. The strength of the model is in its ability to describe the whole
      spectrum of reaction types and unify them under a single general paradigm.
      Moreover, it allows one to understand, conceptualize, and predict chemical
      reactivity in a general as well as specific manner. As such, VBSCD is a valuable
      model. The model has been largely tested on various systems in the gas phase both
      qualitatively and quantitatively. However, its application to reactions in
      solution was given less attention because of the difficulties to represent
      solvent reorganization and estimate non-equilibrium solvation effects, which, on
      the basis of the model, are expected to be fundamental. The recently developed
      valence-bond molecular mechanics (VB/MM) method overcomes these difficulties
      because it involves explicit solvent molecules and thus allows quantitative
      examination of these solvent effects. This work presents a study of the identity
      S(N)2 reaction X(-) + H(3)CX --> XCH(3) + X(-); (X = F, Cl, Br, I) in aqueous
      solution. The various parameters that form the VBSCD model are calculated and
      compared with the corresponding model's estimated values. A relatively good
      agreement between the calculated and estimated values is found. It is shown that
      when facing quantitative considerations, the picture may not be as simplistic as
      in the qualitative study; yet, the fundamental nature of the description is
      unaffected. This indicates that combined together, the VB/MM approach and the
      VBSCD model offer a very powerful tool to study reactions in complex systems and
      understand their reactivity patterns.

PMID- 18620379
TI  - Novel terphenyls and 3,5-diaryl isoxazole derivatives endowed with growth
      supporting and antiapoptotic properties.
AB  - A new study on terphenyl and diaryl-isoxazole and -isoxazoline derivatives,
      maintaining a common 3-adamantyl-4-hydroxyphenyl moiety, has been conducted to
      find compounds with growth supporting and antiapoptotic properties. Unexpectedly,
      diphenyisoxazole derivatives bearing a nitro group replacing the carboxylic
      function have been found with the highest cell protective activity within the
      series, in complete and in serum-free conditions. Inhibition of apoptosis induced
      by daunorubicin has also been observed for the most active compound.

PMID- 18620380
TI  - Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid
      dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme
      and the potent inhibitor 3,5-dichlorosalicylic acid.
AB  - The crystal structure of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in
      ternary complex with the coenzyme NADP (+) and the potent inhibitor 3,5
      dichlorosalicylic acid was determined at a resolution of 1.8 A. The inhibitor is
      held in place by a network of hydrogen bonding interactions with the active site
      residues Tyr55, His117, and His222. The important role of the nonconserved
      residues Leu54, His222, Leu306, and Leu308 in inhibitor binding and selectivity
      was determined by site-directed mutagenesis.

PMID- 18620381
TI  - Novel indoline-based acyl-CoA:cholesterol acyltransferase inhibitor with
      antiperoxidative activity: improvement of physicochemical properties and
      biological activities by introduction of carboxylic acid.
AB  - A series of novel indoline derivatives with an ionizable moiety were synthesized
      to find a bioavailable acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor with
      antiperoxidative activity. [7-(2,2-Dimethylpropanamido)-4,6-dimethyl-1
      octylindolin-5-yl]acetic acid hemisulfate (2, pactimibe sulfate) with low
      lipophilicity and high water solubility showed good oral absorption and
      inhibitory activity against foam cell formation in THP-1 cells exposed to acetyl
      LDL after differentiation (IC50: 0.3 microM) and an antiperoxidative effect in
      LDL of hypercholesterolemic rabbits (IC50: 1.0 microM). 2 inhibited macrophage,
      hepatic, and intestinal ACAT activity (IC50: 1.9, 0.7, and 0.7 microM,
      respectively). Maximal plasma concentration after oral administration of 2 at 10
      mg/kg was 0.9 microg/mL in rats, 3.0 microg/mL in rabbits, and 11.2 microg/mL in
      dogs. Repeated administration of 2 lowered plasma LDL/VLDL cholesterol in
      hypercholesterolemic rabbits at 1 mg/kg/day, rats and dogs at 3 mg/kg/day, and in
      normocholesterolemic hamsters at 3 mg/kg/day. 2 is a promising candidate for
      antihyperlipidemic and antiatherosclerotic drugs.

PMID- 18620382
TI  - Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2
      pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent
      vascular endothelial growth factor receptor inhibitor.
AB  - Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway has
      emerged as one of the most promising new approaches for cancer therapy. We
      describe herein the key steps starting from an initial screening hit leading to
      the discovery of pazopanib, N(4)-(2,3-dimethyl-2H-indazol-6-yl)-N(4)-methyl-N(2)
      (4-methyl-3-sulfonamidophenyl)-2,4-pyrimidinediamine, a potent pan-VEGF receptor
      (VEGFR) inhibitor under clinical development for renal-cell cancer and other
      solid tumors.

PMID- 18620383
TI  - Mechanistic studies on fast ligand substitution reactions of Pt(II) in different
      ionic liquids: role of solvent polarity and ion-pair formation.
AB  - The effect of several imidazolium-based ionic liquids on the mechanism of a
      classical ligand substitution reaction of [Pt(terpyridine)Cl] (+) with thiourea
      was investigated. A detailed kinetic study as a function of the nucleophile
      concentration and temperature was undertaken under pseudo-first-order conditions
      using stopped-flow techniques. Polarity measurements were performed for the
      employed ionic liquids on the basis of solvatochromic effects, and they show
      similarities with conventional polar solvents. Density-functional theory
      calculations (RB3LYP/LANL2DZp) were employed to predict the ion-pair
      stabilization energy between the ionic components of the ionic liquids and/or
      between the anions of the ionic liquids and the cationic Pt (II) complex. These
      data illustrate how the anions of the ionic liquids can affect the investigated
      substitution reaction. In general, the substitution mechanism in ionic liquids
      was found to have an associative character similar to that in conventional
      solvents. The observed deviations reflect the influence of the ionic liquid on
      the interaction between the anionic component of the liquid and the positively
      charged complex.

PMID- 18620384
TI  - Triazenide complexes of the heavier alkaline earths: synthesis, characterization,
      and suitability for hydroamination catalysis.
AB  - A series of triazenide complexes of the heavier alkaline earths, Ca, Sr and Ba,
      have been synthesized by either protonolysis or salt metathesis routes. Although
      complexes of the form [{Ar 2N 3}M{N(SiMe 3) 2}(THF) n ] (M = Ca, n = 2; M = Sr, n
      = 3; Ar = 2,6-diisopropylphenyl) and [{Ar 2N 3}Ca(I)(THF) 2] 2 could be isolated
      and characterized by X-ray crystallography, solution studies revealed the
      propensity of these species to undergo Schlenk-like redistribution with the
      formation of [{Ar 2N 3} 2M(THF) n ] (M = Ca, n = 1; M = Sr, n = 2). The latter
      compounds have been synthesized independently. In the case of the large barium
      dication, attempts to synthesize the heaviest analogue of the series, [{Ar 2N 3}
      2Ba(THF) n ], failed and led instead to the isolation of the potassium barate
      complex [K{Ar 2N 3}Ba{N(SiMe 3) 2} 2(THF) 4]. Single crystal X-ray diffraction
      studies demonstrated that, although in all the aforementioned cases the
      triazenide ligand binds to the electrophilic group 2 metal centers via
      symmetrical kappa (2)- N, N-chelates, in the latter compound an unprecedented
      bridging mode is observed in which the triazenide ligand coordinates through both
      terminal and internal nitrogen centers. A series of density-functional theory
      computational experiments have been undertaken to assist in our understanding of
      this phenomenon. In further experiments, the calcium and strontium amide
      derivatives [{Ar 2N 3}M{N(SiMe 3) 2}(THF) n ] (M = Ca, n = 2; M = Sr, n = 3)
      proved to be catalytically active for the intramolecular hydroamination of 1
      amino-2,2-diphenylpent-4-ene to form 2-methyl-4,4-diphenylpyrrolidine, with the
      calcium species demonstrating a higher turnover number than the strontium
      analogue ( 2a, TOF = 500 h (-1); 2b, TOF = 75 h (-1)). In these instances,
      because of ambiguities in the structural charcterization of the precatalyst in
      solution, such quantification holds little value and detailed catalytic studies
      have not been conducted.

PMID- 18620385
TI  - Synthesis and characterization of phase-pure manganese(II) and manganese(III)
      silicalite-2.
AB  - Manganese silicalite-2 was synthesized at high pH using the molecular cluster Mn
      12O 12(O 2CCH 3) 16 as a Mn source. The silicalite-2 (ZSM-11) materials were
      synthesized using 3,5-dimethyl- N, N-diethylpiperdinium hydroxide as a structure
      directing agent to produce phase-pure ZSM-11 materials. No precipitation of
      manganese hydroxide was observed, and synthesis resulted in the incorporation of
      up to 2.5 mol % Mn into the silicalite-2 with direct substitution into the
      framework verified by the linear relationship between the unit cell volume and
      loading. The Mn is reduced to Mn (II) during hydrothermal synthesis and
      incorporated into the silicalite-2 framework during calcination at 500 degrees C.
      Further calcination at 750 degrees C does not affect the crystallinity but
      oxidizes essentially all of the Mn (II) to Mn (III) in the framework. The large
      difference in oxidation temperatures between the II and III oxidation states
      provides a means of producing relatively pure manganese(II) and manganese(III)
      silicalite-2 materials for applications such as catalysis.

PMID- 18620386
TI  - Two Dawson-templated three-dimensional metal-organic frameworks based on oxalate
      bridged binuclear cobalt(II)/Nickel(II) SBUs and Bpy linkers.
AB  - The Dawson anion P 2W 18O 62 (6-) has been used as a noncoordinating polyoxoanion
      template for the construction of two metal-organic frameworks, namely, [M 2(bpy)
      3(H 2O) 2(ox)][P 2W 18O 62]2(H 2-bpy). nH 2O (M = Co(II), n = 3 ( 1); M = Ni(II),
      n = 2 ( 2)) (bpy = 4,4'-bipyridine; ox = C 2O 4 (2-)). Single-crystal X-ray
      analysis reveals that both of the structures exhibit 3D host frameworks
      constructed from the oxalate-bridged binuclear superoctahedron secondary building
      units (SBUs) and bpy linkers and the voids of which are occupied by Dawson
      anions, guest bpy, and water molecules. Magnetic studies reveal that there are
      antiferromagnetic exchange interactions among the transition-metal centers in
      compounds 1 and 2. Furthermore, a compound 1-modified carbon paste electrode ( 1
      CPE) displays good electrocatalytic activity toward the reduction of nitrite.

PMID- 18620388
TI  - Self-assembly and characterization of a novel 2D network polymer containing a 60
      membered organotin macrocycle.
AB  - The reaction of 1-(4-carboxyphenyl)-5-mercapto-1 H-tetrazole with trimethyltin
      chloride in the presence of sodium ethoxide in benzene affords a novel 2D
      organotin network structure complex 1, which is an unusual organotin network
      containing a hexanuclear 60-membered organotin macrocycle. The complex has been
      characterized by elemental analysis, IR, and (1)H, (13)C, and (119)Sn NMR
      spectroscopy. Furthermore, we have also characterized the complex by X-ray
      crystallography.

PMID- 18620387
TI  - Redox and structural properties of mixed-valence models for the active site of
      the [FeFe]-hydrogenase: progress and challenges.
AB  - The one-electron oxidations of a series of diiron(I) dithiolato carbonyls were
      examined to evaluate the factors that affect the oxidation state assignments,
      structures, and reactivity of these low-molecular weight models for the H ox
      state of the [FeFe]-hydrogenases. The propanedithiolates Fe 2(S 2C 3H 6)(CO)
      3(L)(dppv) (L = CO, PMe 3, P i-Pr 3) oxidize at potentials approximately 180 mV
      milder than the related ethanedithiolates ( Angew. Chem., Int. Ed. 2007, 46,
      6152). The steric clash between the central methylene of the propanedithiolate
      and the phosphine favors the rotated structure, which forms upon oxidation.
      Electron Paramagnetic Resonance (EPR) spectra for the mixed-valence cations
      indicate that the unpaired electron is localized on the Fe(CO)(dppv) center in
      both [Fe 2(S 2C 3H 6)(CO) 4(dppv)]BF 4 and [Fe 2(S 2C 3H 6)(CO) 3(PMe 3)(dppv)]BF
      4, as seen previously for the ethanedithiolate [Fe 2(S 2C 2H 4)(CO) 3(PMe
      3)(dppv)]BF 4. For [Fe 2(S 2C n H 2 n )(CO) 3(P i-Pr 3)(dppv)]BF 4; however, the
      spin is localized on the Fe(CO) 2(P i-Pr 3) center, although the Fe(CO)(dppv)
      site is rotated in the crystalline state. IR and EPR spectra, as well as redox
      potentials and density-functional theory (DFT) calculations, suggest that the
      Fe(CO) 2(P i-Pr 3) site is rotated in solution, driven by steric factors.
      Analysis of the DFT-computed partial atomic charges for the mixed-valence species
      shows that the Fe atom featuring a vacant apical coordination position is an
      electrophilic Fe(I) center. One-electron oxidation of [Fe 2(S 2C 2H 4)(CN)(CO)
      3(dppv)] (-) resulted in 2e oxidation of 0.5 equiv to give the mu-cyano
      derivative [Fe (I) 2(S 2C 2H 4)(CO) 3(dppv)](mu-CN)[Fe (II) 2(S 2C 2H 4)(mu
      CO)(CO) 2(CN)(dppv)], which was characterized spectroscopically.

PMID- 18620389
TI  - Kinetic evaluation of highly active supported gold catalysts prepared from
      monolayer-protected clusters: an experimental Michaelis-Menten approach for
      determining the oxygen binding constant during CO oxidation catalysis.
AB  - Thiol monolayer-protected Au clusters (MPCs) were prepared using dendrimer
      templates, deposited onto a high-surface-area titania, and then the thiol
      stabilizers were removed under H2/N2. The resulting Au catalysts were
      characterized with transmission electron microscopy, X-ray photoelectron
      spectroscopy, and infrared spectroscopy of adsorbed CO. The Au catalysts prepared
      via this route displayed minimal particle agglomeration during the deposition and
      activation steps. Structural data obtained from the physical characterization of
      the Au catalysts were comparable to features exhibited from a traditionally
      prepared standard Au catalyst obtained from the World Gold Council (WGC). A
      differential kinetic study of CO oxidation catalysis by the MPC-prepared Au and
      the standard WGC catalyst showed that these two catalyst systems have essentially
      the same reaction order and Arrhenius apparent activation energies (28 kJ/mol).
      However, the MPC-prepared Au catalyst shows 50% greater activity for CO
      oxidation. Using a Michaelis-Menten approach, the oxygen binding constants for
      the two catalyst systems were determined and found to be essentially the same
      within experimental error. To our knowledge, this kinetic evaluation is the first
      experimental determination of oxygen binding by supported Au nanoparticle
      catalysts under working conditions. The values for the oxygen binding equilibrium
      constant obtained from the Michaelis-Menten treatment (ca. 29-39) are consistent
      with ultra-high-vacuum measurements on model catalyst systems and support density
      functional theory calculations for oxygen binding at corner or edge atoms on Au
      nanoparticles and clusters.

PMID- 18620391
TI  - Evolution of standing mesochannels on porous anodic alumina substrates with
      designed conical holes.
AB  - We report the formation of standing mesochannels simply by spin-coating a
      precursor solution onto a PAA (porous anodic alumina) substrate with designed
      conical holes, utilizing exactly the same precursors and reaction conditions that
      form two-dimensional (2D) hexagonal mesoporous SBA-15-type films. When the aspect
      ratios of the conical holes are lower, the sponge-like mesopores are generated
      within the conical holes. Such a formation of sponge-like mesostructures truly
      acts as a trigger for the evolution of perpendicularly oriented and tilted
      mesochannels. On the other hand, when the PAA substrates with high-aspect cones
      are used, the mesochannels are stacked like a doughnut within the conical holes,
      which leads to parallel orientations of the mesochannels in the continuous film
      region.

PMID- 18620392
TI  - Antiaromatic spacer-bridged bisfluorenyl dications generated by superacid induced
      ionization.
AB  - Derivatives of the dication of tetrabenzo[5.5]fulvalene were prepared with phenyl
      and ethynyl spacers through ionization of the appropriate bis-methylethers. The
      antiaromaticity shown by the parent dication was demonstrated for these dications
      with spacers, although it was attenuated by the presence of the spacer. It was
      substantially greater than that of fluorenyl monocations with similar
      substituents. Antiaromaticity was evaluated through comparison of (1)H NMR shifts
      with those of acyclic analogues, through nucleus independent chemical shifts, and
      through magnetic susceptibility exaltation. Although the fluorenyl systems are
      separated by spacers, the antiaromaticity of one system is affected by the other
      remote fluorenyl system. An explanation for this interaction may lie in the
      ability of a remote cationic substituent to attenuate delocalization in the
      spacer. The use of spacers is designed to prevent side reactions in less stable
      antiaromatic dications, allowing exploration of a number of species that have
      previously been inaccessible.

PMID- 18620393
TI  - Combined experimental and theoretical study of the mechanism and
      enantioselectivity of palladium- catalyzed intermolecular Heck coupling.
AB  - The asymmetric Heck reaction using P,N-ligands has been studied by a combination
      of theoretical and experimental methods. The reaction follows Halpern-style
      selectivity; that is, the major isomer is produced from the least favored form of
      the pre-insertion intermediate. The initially formed Ph-Pd(P,N) species prefers a
      geometry with the phenyl trans to N. However, the alternative form, with Ph trans
      to P, is much less stable but much more reactive. In the preferred transition
      state, the phenyl moiety is trans to P, but significant electron density has been
      transferred to the alkene carbon trans to N. The steric interactions in this
      transition state fully account for the enantioselectivity observed with the
      ligands studied. The calculations also predict relative reactivity and nonlinear
      mixing effects for the investigated ligands; these predictions are fully
      validated by experimental testing. Finally, the low conversion observed with some
      catalysts was found to be caused by inactivation due to weak binding of the
      ligand to Pd(0). Adding monodentate PPh3 alleviated the precipitation problem
      without deteriorating the enantioselectivity and led to one of the most effective
      catalytic systems to date.

PMID- 18620390
TI  - Atomistic insights into rhodopsin activation from a dynamic model.
AB  - Rhodopsin, the light sensitive receptor responsible for blue-green vision, serves
      as a prototypical G protein-coupled receptor (GPCR). Upon light absorption, it
      undergoes a series of conformational changes that lead to the active form,
      metarhodopsin II (META II), initiating a signaling cascade through binding to the
      G protein transducin (G(t)). Here, we first develop a structural model of META II
      by applying experimental distance restraints to the structure of lumi-rhodopsin
      (LUMI), an earlier intermediate. The restraints are imposed by using a
      combination of biased molecular dynamics simulations and perturbations to an
      elastic network model. We characterize the motions of the transmembrane helices
      in the LUMI-to-META II transition and the rearrangement of interhelical hydrogen
      bonds. We then simulate rhodopsin activation in a dynamic model to study the path
      leading from LUMI to our META II model for wild-type rhodopsin and a series of
      mutants. The simulations show a strong correlation between the transition
      dynamics and the pharmacological phenotypes of the mutants. These results help
      identify the molecular mechanisms of activation in both wild type and mutant
      rhodopsin. While static models can provide insights into the mechanisms of ligand
      recognition and predict ligand affinity, a dynamic model of activation could be
      applicable to study the pharmacology of other GPCRs and their ligands, offering a
      key to predictions of basal activity and ligand efficacy.

PMID- 18620394
TI  - Isopenicillin N synthase mediates thiolate oxidation to sulfenate in a
      depsipeptide substrate analogue: implications for oxygen binding and a link to
      nitrile hydratase?
AB  - Isopenicillin N synthase (IPNS) is a nonheme iron oxidase that catalyzes the
      central step in the biosynthesis of beta-lactam antibiotics: oxidative
      cyclization of the linear tripeptide delta-L-alpha-aminoadipoyl-L-cysteinyl-D
      valine (ACV) to isopenicillin N (IPN). The ACV analogue delta-L-alpha
      aminoadipoyl-L-cysteine (1-(S)-carboxy-2-thiomethyl)ethyl ester (ACOmC) has been
      synthesized as a mechanistic probe of IPNS catalysis and crystallized with the
      enzyme. The crystal structure of the anaerobic IPNS/Fe(II)/ACOmC complex was
      determined to 1.80 A resolution, revealing a highly congested active site region.
      By exposing these anaerobically grown crystals to high-pressure oxygen gas, an
      unexpected sulfenate product has been observed, complexed to iron within the IPNS
      active site. A mechanism is proposed for formation of the sulfenate-iron complex,
      and it appears that ACOmC follows a different reaction pathway at the earliest
      stages of its reaction with IPNS. Thus it seems that oxygen (the cosubstrate)
      binds in a different site to that observed in previous studies with IPNS,
      displacing a water ligand from iron in the process. The iron-mediated conversion
      of metal-bound thiolate to sulfenate has not previously been observed in
      crystallographic studies with IPNS. This mode of reactivity is of particular
      interest when considered in the context of another family of nonheme iron
      enzymes, the nitrile hydratases, in which post-translational oxidation of two
      cysteine thiolates to sulfenic and sulfinic acids is essential for enzyme
      activity.

PMID- 18620395
TI  - A rigorous framework to interpret water relaxivity. The case study of a Gd(III)
      complex with an alpha-cyclodextrin derivative.
AB  - We present a general theoretical framework suitable for an economical, but
      rigorous, analysis of the relaxivity and EPR data of paramagnetic metal
      complexes. This framework is based on the so-called Grenoble method that properly
      accounts for the fluctuations of the "static" zero-field splitting Hamiltonian
      and avoids the misinterpretation of experimental data, which occurs with the
      Solomon, Bloembergen, and Morgan (SBM) formalism and may lead to erroneous
      conclusions. The applicability of the SBM approximation is discussed. Our
      approach is implemented in the case of a new Gd(3+) chelate with a cyclodextrin
      derivative ligand hexakis(2-O-carboxymethyl-3,6-anhydro)-alpha-cyclodextrin
      (ACX), designed to obtain lanthanide complexes of enhanced stability in
      comparison to natural cyclodextrins. The introduction of carboxymethyl units on
      the six residual hydroxyl groups of an alpha-per-3,6-anhydro cyclodextrin leads
      to mono- and binuclear Ln(3+) complexes with log beta(110) approximately = 7.5.
      The GdACX complex induces large water proton relaxivity in 0.1 M KCl aqueous
      solution. The molecular parameters governing the longitudinal (r1) and transverse
      (r2) relaxivities above 1 T are obtained through simple SBM-like theoretical
      expressions and complementary experimental techniques. The metal hydration state,
      the translational diffusion coefficient of the complex, and its rotational
      correlation time are derived from luminescence lifetime studies, pulse-field
      gradient NMR, and deuteron quadrupolar relaxation, respectively. The high
      relaxivity induced by the GdACX complex is attributed to its high hydration state
      in the presence of potassium ions and to a rotational correlation time lengthened
      by the hydrophilic character of the ACX scaffold.

PMID- 18620396
TI  - Hydrogen-bond-induced hysteresis in the compression/relaxation of monolayer
      films.
AB  - Two stereoisomers of surfactants were synthesized in which a diketopiperazine
      ring was inserted between a hydrocarbon chain (of variable length) and an anionic
      headgroup. It was found (by HPLC, conductivity, surface tension, and diffusion
      NMR) that these compounds have low solubilities in water, remarkably high Krafft
      temperatures, and low critical micelle concentrations. Of particular interest
      were the pressure/area isotherms of insoluble monolayers of nonionic analogues of
      the amphiphiles. These isotherms showed an unprecedented hysteresis but only
      during the first compression/relaxation cycle. Additional cycles were normal in
      that they lacked the original hysteresis. These results were attributed to
      diketopiperazine rings that initially lie flat on the water surface at the
      air/water interface. Compression flips the diketopiperazine rings so that they
      now reside roughly perpendicular to the interface in a stable hydrogen-bonded
      orientation where the rings occupy far less space.

PMID- 18620397
TI  - Bidirectional transfer of phenyl and methyl groups between Pt(IV) and boron in
      platinum dipyridylborato complexes.
AB  - In the presence of weakly Lewis basic DMSO methyl group migration between B and
      PtIV in dipyridylborato trihydrocarbyl PtIV complexes is reversible; the
      preferred direction of Ph group migration in THF solution is from PtIV to B.

PMID- 18620398
TI  - Interstrand cross-link formation in duplex and triplex DNA by modified
      pyrimidines.
AB  - DNA interstrand cross-links have important biological consequences and are useful
      biotechnology tools. Phenylselenyl substituted derivatives of thymidine (1) and 5
      methyl-2'-deoxycytidine (5) produce interstrand cross-links in duplex DNA when
      oxidized by NaIO4. The mechanism involves a [2,3]-sigmatropic rearrangement of
      the respective selenoxides to the corresponding methide type intermediates, which
      ultimately produce the interstrand cross-links. Determination of the rate
      constants for the selenoxide rearrangements indicates that the rate-determining
      step for cross-linking is after methide formation. Cross-linking by the thymidine
      derivative in duplex DNA shows a modest kinetic preference when flanked by
      pyrimidines as opposed to purines. In contrast, the rate constant for cross-link
      formation from 5 opposite dG in duplex DNA is strongly dependent upon the
      flanking sequence and, in general, is at least an order of magnitude slower than
      that for 1 in an otherwise identical sequence. Introduction of mispairs at the
      base pairs flanking 5 or substitution of the opposing dG by dI significantly
      increases the rate constant and yield for cross-linking, indicating that stronger
      hydrogen bonding between the methide derived from it and dG compared to dA and
      the respective electrophile derived from 1 limits reaction by increasing the
      barrier to rotation into the required syn-conformation. Incorporation of 1 or 5
      in triplex forming oligonucleotides (TFOs) that utilize Hoogsteen base pairing
      also yields interstrand cross-links. The dC derivative produces ICLs
      approximately 10x faster than the thymidine derivative when incorporated at the
      5'-termini of the TFOs and higher yields when incorporated at internal sites. The
      slower, less efficient ICL formation emanating from 1 is attributed to reaction
      at N1-dA, which requires local melting of the duplex. In contrast, 5 produces
      cross-links by reacting with N7-dG. The cross-linking reactions of 1 and 5
      illustrate the versatility and utility of these molecules as mechanistic probes
      and tools for biotechnology.

PMID- 18620399
TI  - Identification and characterization of the precursor of chicken matrix
      metalloprotease 2 (pro-MMP-2) in hen egg.
AB  - Using zymography and mass spectrometry, we identified for the first time the
      precursor of chicken matrix metalloprotease 2 (pro-MMP-2) as a complex with TIMP
      2 (tissue inhibitor of metalloproteinases) in egg white and yolk. Real-time
      polymerase chain reaction confirmed that MMP-2 and its inhibitors TIMP-2 and TIMP
      3 were expressed all along the oviduct and in the liver of laying hens. We also
      demonstrated that the processing of pro-MMP-2 into mature MMP-2 by serine
      proteases does not occur in vivo, although purified pro-MMP-2 undergoes
      proteolytic maturation by these proteases in vitro. Moreover, the relative pro
      MMP-2 activity assessed by gelatin zymography was shown to decrease in egg white
      during the storage of unfertilized or fertilized eggs. However, the mature form
      of 62 kDa MMP-2 could not be detected. The fact that MMP-2 is found as a proform
      in fresh eggs suggests that the activity of this metalloprotease is regulated
      under specific conditions during embryonic development.

PMID- 18620400
TI  - Protein quality, antigenicity, and antioxidant activity of soy-based foodstuffs.
AB  - Commercial soy-based foodstuffs, including beverages ( n = 15), cow's milk
      supplemented with soy isoflavones ( n = 1), snacks ( n = 1), and biscuits ( n =
      2), were analyzed to find any link between alterations in protein quality, safety
      (antigenicity), functionality (antioxidant activity), and food processing.
      Protein content was analyzed by the Kjeldhal method and available lysine by OPA
      assay. Chromatographic (RP-HPLC) and electrophoretic (SDS-PAGE) protein profiles
      were obtained to monitor modifications in the structure of soy allergens. The
      antigenicity was estimated by immunoblotting against soy total antibodies. Total
      phenol content was measured by Folin-Ciocalteu, while peroxyl radical scavenging
      activity of the sample was determined by ORAC FL assay. Protein content did not
      differ of those declared by the producers. Lysine availability was higher in
      liquid soy beverages compared to that in other soy foodstuffs studied here. 7S
      and 11S soy allergens were detected by RP-HPLC and SDS-PAGE, respectively. Both
      data indicated changes in soy protein patterns due to processing of instant
      powdered soymilk, soy snacks, and biscuits. Immunoblotting assay showed
      modifications in the antigenic response of these foodstuffs based on soy,
      suggesting that their processing had altered the structure of soy allergens. RP
      HPLC, SDS-PAGE, and immunoblotting resulted in adequate analytical approaches for
      detecting changes in protein structure due to processing and adulteration.
      Protein quality, antigenicity, and antioxidant activity of soy products can be
      affected as a function of the intensity of the thermal processing.

PMID- 18620401
TI  - Evaluation of the umami taste intensity of green tea by a taste sensor.
AB  - A method for evaluating the umami taste intensity of green tea by a taste sensor
      system was established. Interference in the measurement from catechins was solved
      by removing the catechins from sample solutions with poly(vinylpolypyrrolidone).
      A 5.00 mM aqueous solution of glutamic acid monosodium salt was used as the
      standard solution. Sensor outputs were converted into EIT uma (estimated
      intensity of taste concerning umami) values. One unit on the EIT uma scale was
      defined as the amount of the sensor output corresponding to a difference in 1.2
      times the concentration of the standard substance (glutamic acid monosodium
      salt). The umami taste intensity of green tea was classified into six grades on
      the EIT uma scale. Sensory tests proved that the EIT uma value had a high
      correlation to the human gustatory sense.

PMID- 18620402
TI  - Comparison of nutritional traits variability in selected eighty-seven inbreds
      from Chinese maize (Zea mays L.) germplasm.
AB  - Among cereals, only maize has not only a high amount of carotenoids, tocopherols,
      and oil content but also is rich in starch and protein content compared with
      other major food crops, such as rice and wheat. The present investigation was
      made primarily to assess the genetic variability for nutritionally important
      traits in 87 elite maize inbreds representing major heterotic groups in China.
      Carotenoid and tocopherol fractions were measured by high-performance liquid
      chromatography (HPLC), whereas oil, starch, and protein contents were detected by
      a VECTER22/N near-infrared analyzer. Significant interactions between genotypes
      and years were observed for all the traits. The pooled mean values of beta
      carotene, beta-cryptoxanthin, alpha-carotene, lutein, zeaxanthin, and total
      carotenoids were 0.449, 0.876, 0.121, 5.803, 3.048, and 10.298 microg g (-1),
      respectively, whereas the combined mean performance of alpha-tocopherol, gamma
      tocopherol, delta-tocopherol, and total tocopherols were 23.98, 32.90, 2.189, and
      59.55 microg g (-1), respectively. The average protein, starch, and oil contents
      were observed to be 12.28, 64.51, and 3.55%, respectively. High level of
      heritability estimates were observed for all the traits and ranged from 65.6%
      (protein content) to 92.5% (alpha/gamma-tocopherol ratio). Most of the traits
      studied in this experiment were either significantly positive correlated or
      independent. The present finding exhibits substantial opportunities to the
      breeders for improvement of these traits in maize cultivars and also suggests
      further exploration of a new source of elite breeding stocks containing a high
      level of these nutritionally important compounds. Finally, these findings may
      also help in biofortification of maize.

PMID- 18620403
TI  - Impact of high-pressure carbon dioxide combined with thermal treatment on
      degradation of red beet (Beta vulgaris L.) pigments.
AB  - A combined high-pressure carbon dioxide (HP-CO 2) and thermal degradation
      reaction of betanin and isobetanin in aqueous solution was investigated and can
      be described by a first-order decay. At 45 degrees C, the degradation rate
      constant ( k) for each pigment component significantly increased (the half-life (
      t 1/2) decreased, p < 0.05) with elevated pressure. Furthermore, HP-CO 2
      treatment led to lower k values (higher t 1/2 values) than thermal treatment.
      However, k and t 1/2 values approached those of thermal treatment when the
      pressure was >30 MPa combined with temperatures exceeding 55 degrees C. Moreover,
      betanin was more stable than isobetanin under HP-CO 2. E a values ranged from
      94.01 kJ/mol for betanin and 97.16 kJ/mol for isobetanin at atmospheric pressure
      to 170.83 and 142.69 kJ/mol at 50 MPa, respectively. A higher pressure and
      temperature as well as longer exposure time resulted in higher values of L*, b*,
      C*, and h degrees . HP-CO 2 induced more degradation products from betanin and
      isobetanin than thermal treatment with an identical temperature and exposure
      time.

PMID- 18620404
TI  - Extrinsic labeling method may not accurately measure Fe absorption from cooked
      pinto beans (Phaseolus vulgaris): comparison of extrinsic and intrinsic labeling
      of beans.
AB  - Isotopic labeling of food has been widely used for the measurement of Fe
      absorption in determining requirements and evaluating the factors involved in Fe
      bioavailability. An extrinsic labeling technique will not accurately predict the
      total Fe absorption from foods unless complete isotopic exchange takes place
      between an extrinsically added isotope label and the intrinsic Fe of the food. We
      examined isotopic exchange in the case of both white beans and colored beans
      (Phaseolus vulgaris) with an in vitro digestion model. There are significant
      differences in (58)Fe/(56)Fe ratios between the sample digest supernatant and the
      pellet of extrinsically labeled pinto bean. The white bean digest shows
      significantly better equilibration of the extrinsic (58)Fe with the intrinsic
      (56)Fe. In contrast to the extrinsically labeled samples, both white and red
      beans labeled intrinsically with (58)Fe demonstrated consistent ratios of
      (58)Fe/(56)Fe in the bean meal, digest, supernatant, and pellet. It is possible
      that the polyphenolics in the bean seed coat may bind Fe and thus interfere with
      extrinsic labeling of the bean meals. These observations raise questions on the
      accuracy of studies that used extrinsic tags to measure Fe absorption from beans.
      Intrinsic labeling appears necessary to accurately measure Fe bioavailability
      from beans.

PMID- 18620405
TI  - Influence of complexation between amylose and a flavored model sponge cake on the
      degree of aroma compound release.
AB  - Flavoring is used in the food industry to reinforce the aroma profile of baked
      cereal goods. During the processing of such products, interactions between starch
      and aroma compounds can occur, and this may have an impact on aroma release and
      perception. In the present study, 20 aroma compounds were tested to establish
      whether they formed complexes with amylose. The structure of the complexes was
      determined by wide-angle X-ray scattering (WAXS). A cocomplexation study proved
      that several complexing compounds could be present in the same crystalline
      aggregate. WAXS and differential scanning calorimetry (DSC) experiments were
      performed in a flavored model sponge cake at different steps of processing and
      showed that aroma compounds might form complexes with amylose in a sponge cake as
      they can do in simple system containing only amylose. Some of the aroma compounds
      trapped in the sponge cake were quantified, and their release behavior was
      followed by headspace analysis. The V-type structure could partly explain aroma
      retention in the product and the rate of aroma release.

PMID- 18620406
TI  - Synthesis, crystal structure, and insecticidal activity of novel N-alkyloxyoxalyl
      derivatives of 2-arylpyrrole.
AB  - Two series of novel N-alkyloxyoxalyl derivatives of 2-arylpyrrole were
      synthesized, and their structures were characterized by (1)H NMR spectroscopy,
      elemental analysis, and single-crystal X-ray diffraction analysis. The
      insecticidal activities of the new compounds were evaluated. The results of
      bioassays indicated that some of these title compounds exhibited excellent
      insecticidal activities, and their insecticidal activities against oriental
      armyworm, mosquito, and spider mite are comparable to those of the commercialized
      Chlorfenapyr.

PMID- 18620407
TI  - Fluorescence-based method, exploiting lipofuscin, for real-time detection of
      central nervous system tissues on bovine carcasses.
AB  - The removal of central nervous system (CNS) tissues as part of bovine spongiform
      encephalopathy (BSE) risk material is one of the highest priority tasks to avoid
      contamination of the human food chain with BSE. No currently available method
      enables the real-time detection of possible CNS tissue contamination on carcasses
      during slaughter. The fluorescent pigment lipofuscin is a heterogeneous, high
      molecular weight material that has been shown to be enriched in high
      concentrations in neuronal tissues. In this study, lipofuscin fluorescence was
      investigated as a marker for real-time detection of CNS contamination. Front
      faced fluorescence spectra of brain and spinal cord samples from 11 cattle gave
      identical, reproducible fluorescence signal patterns with high intensities. The
      specificity of these spectra was assessed by investigating 13 different non-CNS
      tissues enabling the differentiation of brain and spinal cord by signal intensity
      and structure of the spectra, respectively. Small quantities of bovine spinal
      cord were reliably detected in the presence of raw bovine skeletal muscle, fat,
      and vertebrae. The presented data are a fundamental basis for the development of
      a prototype device allowing real-time monitoring of CNS tissue contamination on
      bovine carcasses and meat cuts.

PMID- 18620408
TI  - Proteomic analysis of lupin seed proteins to identify conglutin Beta as an
      allergen, Lup an 1.
AB  - Lupin products may be valuable as human foods because of their high protein
      content and potential anticholesterolemic properties. However, a small percentage
      of the population is allergic to lupin. In this study, we use in vitro IgE
      binding and mass spectrometry to identify conglutin beta, a major storage
      protein, as an allergen in seeds of Lupinus angustifolius and Lupinus albus.
      Purification of conglutin beta from L. angustifolius flour confirmed that serum
      IgE binds to this protein. Where IgE in sera recognized lupin proteins on Western
      blots, it recognized conglutin beta, suggesting this protein is a major allergen
      for lupin. The L. angustifolius conglutin beta allergen has been designated Lup
      an 1 by the International Union of Immunological Societies (IUIS) allergen
      nomenclature subcommittee.

PMID- 18620409
TI  - Hypolipidemic effect in cholesterol-fed rats of a soluble fiber-rich product
      obtained from cocoa husks.
AB  - A new soluble cocoa fiber product (SCFP), obtained after enzymatic treatment of
      cocoa husks, was characterized and its potential health effects studied in an
      animal model of dietary-induced hypercholesterolemia. The SCFP was rich in
      soluble dietary fiber (DF) and antioxidant polyphenols. Consumption of a
      cholesterol-rich diet containing the SCFP as a source of DF resulted in lower
      food intake and body weight gain in comparison with control groups consuming
      cholesterol-free or cholesterol-rich diets with cellulose as DF. The cholesterol
      rich diet caused remarkable hypercholesterolemia. However, the SCFP diminished
      the negative impact of the cholesterol-rich diet, buffering the decrease of high
      density lipoprotein-cholesterol, and the increase of total and low density
      lipoprotein-cholesterol levels, and lipid peroxidation (malondialdehyde levels)
      induced by the fatty diet. The SCFP also decreased triglyceride levels to values
      lower than those in the group fed the cholesterol-free diet. These results put
      forward the potential application of the SCFP as a dietary supplement or
      functional food ingredient.

PMID- 18620410
TI  - Effects of ultra-high-pressure homogenization treatment on the lipolysis and
      lipid oxidation of milk during refrigerated storage.
AB  - Free fatty acid (FFA) release and quantification and lipid oxidation extent of
      ultra-high-pressure homogenized (UHPH) milk samples were evaluated to assess the
      effect of UHPH on the susceptibility of milk lipids to lipolysis and oxidation.
      Milk was UHPH-treated at 200 and 300 MPa with inlet temperatures of 30 and 40
      degrees C. UHPH-treated samples were compared to high-pasteurized milk (PA; 90
      degrees C, 15 s). Results showed that all FFA increased significantly during
      storage only in 200 MPa samples. Lipid oxidation was measured as an accumulation
      of lipid hydroperoxides as the primary oxidation product and malondialdehyde and
      hexanal as the secondary oxidation products. Samples treated at 300 MPa presented
      higher malondialdehyde and hexanal content compared to 200 MPa treated-samples
      and to PA milk.

PMID- 18620411
TI  - Effect of centrifugal ultrafiltration on the composition of aqueous extracts of
      saffron spice (Crocus sativus L.).
AB  - The purpose of this research was to study the effect of centrifugal
      ultrafiltration (UF) on the composition of aqueous extracts of saffron spice. The
      contents of seven crocetin esters, picrocrocin, and two kaempferol glycosides
      were analyzed by UV-vis and HPLC in the filtrate and retentate fractions from 16
      centrifugal filter devices with regenerated cellulose (RC) and polyethersulfone
      (PES) membranes ranging from 1-100 kDa nominal molecular weight cutoff (MWCO).
      The separation of crocetin esters from picrocrocin and their concentration with
      centrifugal UF have been demonstrated. A great heterogeneity of results regarding
      devices with equal MWCO was found that could not be related to the membrane
      material or manufacturer. Four devices of 5 and 10 kDa MWCO, three of which had
      RC membranes, showed the best results. The device having the lowest MWCO also
      showed a potential to obtain picrocrocin without crocetin esters and could be
      considered in successive UF steps. The less polar crocetin esters were rejected
      better than the others.

PMID- 18620412
TI  - Optimization of color and antioxidant activity of peach and nectarine puree:
      scale-up study from pilot to industrial plant.
AB  - The effects of an innovative process for the manufacture of peach and nectarine
      purees on the main quality indices, namely, color, consistency, carotenoid and
      phenolic content, and antioxidant activity, were studied using a peach cultivar
      that is optimal for nectar processing (cv. Redhaven) and peach and nectarine
      varieties that undergo a faster browning degradation. The innovative process,
      operating the pulping/finishing step at room temperature, was compared to the
      traditional process of hot pulping/finishing. The study comprised initial trials
      on a pilot plant scale and scaling up to industrial production of the puree and
      nectar. The quality of products was analyzed at the time of production and as a
      function of storage of both the puree and the nectar. With respect to the
      traditional process, the new process, scaled up to industrial levels, improved
      the color of peach and nectarine products (by increasing the L* value and
      decreasing the a* value), whatever the variety studied; maintained almost the
      same levels of carotenoids, hydroxycinnamates, flavan-3-ols, and flavonols; and
      reduced the level of cyanidin 3-O-glucoside. The presence of cyanidin 3-O
      glucoside was correlated to an unstable and undesirable red hue of the products
      (even if its concentration was very low in all products), and the decreased level
      obtained by the innovative process was considered to be positive. On the basis of
      these results, new technology can be proposed for the processing of fruit
      varieties that are not suitable for puree production using traditional
      technology. This opens up two possibilities: (a) utilization of fresh market
      fruit surplus and (b) processing of selected fruit varieties that are rich in
      antioxidants but have a high browning potential, such as the Stark Red Gold
      nectarine. Furthermore, as the positive impact of the new technology is optimal
      at the beginning of storage, it is particularly suitable for fruit-based products
      with a short shelf life.

PMID- 18620413
TI  - Cooking decreases observed perfluorinated compound concentrations in fish.
AB  - Dietary intake is a major route of exposure to perfluorinated compounds (PFCs).
      Although fish and seafood contribute significantly to total dietary exposure to
      these compounds, there is uncertainty with respect to the effect of cooking on
      PFC concentrations in these foods. Eighteen fish species purchased from markets
      in Toronto, Mississauga, and Ottawa, Canada were analyzed for
      perfluorooctanesulfonamide (PFOSAs)-based fluorochemicals and perfluorinated
      acids (PFAs) in raw and cooked (baked, boiled, fried) samples. Of 17 analytes,
      perfluorooctanesulfonic acid (PFOS) was detected most frequently; concentrations
      ranged from 0.21 to 1.68 ng/g ww in raw and cooked samples. PFOSAs were detected
      only in scallops at concentrations ranging from 0.20 ng/g ww to 0.76 ng/g ww.
      Total concentrations of PFAs in samples were 0.21 to 9.20 ng/g ww, respectively,
      consistent with previous studies. All cooking methods reduced PFA concentrations.
      Baking appeared to be the most effective cooking method; after baking samples for
      15 min at 163 C (325 degrees F), PFAs were not detected in any of the samples.
      The margin of exposures (MOE) between the toxicological points of reference and
      the dietary intake of perfluorocarboxylates (PFCAs) and PFOS in fish and seafood
      muscle tissue were greater than 4 orders of magnitude. This indicates that
      reducing consumption of fish muscle tissue is not warranted on the basis of PFC
      exposure concerns at the reported levels of contamination, even for high fish
      consuming populations.

PMID- 18620414
TI  - Total synthesis of (+/-)-2-O-methylneovibsanin H.
AB  - The total synthesis of (+/-)-2- O-methylneovibsanin H was achieved in 12 steps.
      An acid-catalyzed, one-pot, four-step cascade reaction was key to the concise
      total synthesis, lending support to the proposed biosynthesis.

PMID- 18620416
TI  - Cyclooligomerization of a helix-bearing template into macrocycles bearing
      multiple helices.
AB  - Cyclooligomerization was investigated for separating and spatially arranging
      helical peptides as discontinuous surfaces. Tetrapeptide H-[Ile-Ser-Lys(Ox)]-OH,
      containing a turn-inducing oxazole constraint, was connected through its lysine
      side chain via a beta-alanine linker to the C-terminus of a two-turn helical
      nonapeptide Ac-(cyclo-4,8)-LRL [KARAD](Aib). The resulting helix-appended
      template was self-condensed and cyclized to a library of macrocycles ( n = 2-6)
      containing multiple (2-6) helices. An NMR structure shows retention of alpha
      helicity in the cyclotrimer ( n = 3).

PMID- 18620415
TI  - Water-mediated catalyst preactivation: an efficient protocol for C-N cross
      coupling reactions.
AB  - A protocol for forming a highly active Pd(0) catalyst from Pd(OAc) 2, water, and
      biaryldialkylphosphine ligands has been developed. This protocol generates a
      catalyst system, which exhibits excellent reactivity and efficiency in the
      coupling of a variety of amides and anilines with aryl chlorides.

PMID- 18620417
TI  - In silico drug profiling of the human kinome based on a molecular marker for
      cross reactivity.
AB  - Protein kinases are paradigmatic targets in molecular cancer therapy. Affinity
      profiles of kinase drug inhibitors are of considerable interest to assess and
      modulate clinical drug impact. In the initial stages of discovery, a thorough
      experimental screening of lead compound libraries becomes critically limited by
      the size of the kinase sample. This work introduces a computational screening
      approach which provides a tool for extensive screening that uses experimentally
      obtained small-scale profiles as input data and makes predictions for a larger
      kinase set. These predictions result from a propagation of the reduced profile,
      exploiting a structural comparison of kinases based on a feature-similarity
      matrix. The comparison focuses on a molecular marker for specificity and
      promiscuity of kinase inhibitors. Our approach enables the computational high
      throughput screening of entire libraries of compounds to search for suitable
      leads, mapping their inhibitory impact on a sizable sample of the human kinome.
      Our in silico tool is validated by contrasting predictions against reported high
      throughput screening experiments.

PMID- 18620418
TI  - Structural characterization of a 140 degrees domain movement in the two-step
      reaction catalyzed by 4-chlorobenzoate:CoA ligase.
AB  - Members of the adenylate-forming family of enzymes play a role in the metabolism
      of halogenated aromatics and of short, medium, and long chain fatty acids, as
      well as in the biosynthesis of menaquinone, peptide antibiotics, and peptide
      siderophores. This family includes a subfamily of acyl- and aryl-CoA ligases that
      catalyze thioester synthesis through two half-reactions. A carboxylate substrate
      first reacts with ATP to form an acyl-adenylate. Subsequent to the release of the
      product PP i, the enzyme binds CoA, which attacks the activated acyl group to
      displace AMP. Structural and functional studies on different family members
      suggest that these enzymes alternate between two conformations during catalysis
      of the two half-reactions. Specifically, after the initial adenylation step, the
      C-terminal domain rotates by approximately 140 degrees to adopt a second
      conformation for thioester formation. Previously, we determined the structure of
      4-chlorobenzoate:CoA ligase (CBL) in the adenylate forming conformation bound to
      4-chlorobenzoate. We have determined two new crystal structures. We have
      determined the structure of CBL in the original adenylate-forming conformation,
      bound to the adenylate intermediate. Additionally, we have used a novel product
      analogue, 4-chlorophenacyl-CoA, to trap the enzyme in the thioester-forming
      conformation and determined this structure in a new crystal form. This work
      identifies a novel binding pocket for the CoA nucleotide. The structures
      presented herein provide the foundation for biochemical analyses presented in the
      accompanying manuscript in this issue [Wu et al. (2008) Biochemistry 47, 8026
      8039]. The complete characterization of this enzyme allows us to provide an
      explanation for the use of the domain alternation strategy by these enzymes.

PMID- 18620419
TI  - Interaction of recombinant surfactant protein D with lipopolysaccharide:
      conformation and orientation of bound protein by IRRAS and simulations.
AB  - Effective innate host defense requires early recognition of pathogens. Surfactant
      protein D (SP-D), shown to play a role in host defense, binds to the
      lipopolysaccharide (LPS) component of Gram-negative bacterial membranes. Binding
      takes place via the carbohydrate recognition domain (CRD) of SP-D. Recombinant
      trimeric neck+CRDs (NCRD) have proven valuable in biophysical studies of specific
      interactions. Although X-ray crystallography has provided atomic level
      information on NCRD binding to carbohydrates and other ligands, molecular level
      information about interactions between SP-D and biological ligands under
      physiologically relevant conditions is lacking. Infrared reflection-absorption
      spectroscopy (IRRAS) provides molecular structure information from films at the
      air/water interface where protein adsorption to LPS monolayers serves as a model
      for protein-lipid interaction. In the current studies, we examine the adsorption
      of NCRDs to Rd 1 LPS monolayers using surface pressure measurements and IRRAS.
      Measurements of surface pressure, Amide I band intensities, and LPS acyl chain
      conformational ordering, along with the introduction of EDTA, permit
      discrimination of Ca (2+)-mediated binding from nonspecific protein adsorption.
      The findings support the concept of specific binding between the CRD and heptoses
      in the core region of LPS. In addition, a novel simulation method that accurately
      predicts the IR Amide I contour from X-ray coordinates of NCRD SP-D is applied
      and coupled to quantitative IRRAS equations providing information on protein
      orientation. Marked differences in orientation are found when the NCRD binds to
      LPS compared to nonspecific adsorption. The geometry suggests that all three CRDs
      are simultaneously bound to LPS under conditions that support the Ca (2+)
      mediated interaction.

PMID- 18620420
TI  - Role of the cochaperone Tpr2 in Hsp90 chaperoning.
AB  - The molecular chaperones Hsp90 and Hsp70 are highly regulated by various
      cochaperones that participate in the activation of steroid receptors. Here we
      study Tpr2 (also called DjC7), a TPR domain-containing type III J protein
      implicated in steroid receptor chaperoning. We propose that Tpr2 plays a role in
      the Hsp90-dependent chaperoning of the progesterone receptor (PR). Tpr2
      overexpression or knockdown resulted in slight reductions in PR transcriptional
      activity in HeLa cells. Immunoprecipitation and pulldown experiments indicated
      that Tpr2 associates with Hsp90 and Hsp70 complexes, some of which also contain
      the PR. Tpr2 can bind Hsp90 and Hsp70 simultaneously, which is also a property of
      the cochaperone Hop. However, unlike Hop, Tpr2 binding to Hsp70 in the presence
      of Hsp90 is ATP-dependent, and Tpr2 cannot replace Hop in Hsp90 chaperoning in
      vitro or in vivo. While Tpr2 was not detected as a component of PR
      heterocomplexes in cell lysates, purified Tpr2 bound the PR readily.
      Surprisingly, Tpr2 replaced type I and II J proteins in the Hsp90-dependent
      chaperoning of the PR and the protein kinase, Chk1. Unlike other J proteins, Tpr2
      promoted the accumulation of Hsp70 in PR heterocomplexes in the presence of
      Hsp90. Thus, Tpr2 has the potential to regulate PR chaperoning.

PMID- 18620421
TI  - Mechanism of 4-chlorobenzoate:coenzyme a ligase catalysis.
AB  - Within the accompanying paper in this issue (Reger et al. (2008) Biochemistry,
      47, 8016-8025) we reported the X-ray structure of 4-chlorobenzoate:CoA ligase
      (CBL) bound with 4-chlorobenzoyl-adenylate (4-CB-AMP) and the X-ray structure of
      CBL bound with 4-chlorophenacyl-CoA (4-CP-CoA) (an inert analogue of the product
      4-chlorobenzoyl-coenzyme A (4-CB-CoA)) and AMP. These structures defined two CBL
      conformational states. In conformation 1, CBL is poised to catalyze the
      adenylation of 4-chlorobenzoate (4-CB) with ATP (partial reaction 1), and in
      conformation 2, CBL is poised to catalyze the formation of 4-CB-CoA from 4-CB-AMP
      and CoA (partial reaction 2). These two structures showed that, by switching from
      conformation 1 to conformation 2, the cap domain rotates about the domain linker
      and thereby changes its interface with the N-terminal domain. The present work
      was carried out to determine the contributions made by each of the active site
      residues in substrate/cofactor binding and catalysis, and also to test the role
      of domain alternation in catalysis. In this paper, we report the results of
      steady-state kinetic and transient state kinetic analysis of wild-type CBL and of
      a series of site-directed CBL active site mutants. The major findings are as
      follows. First, wild-type CBL is activated by Mg (2+) (a 12-75-fold increase in
      activity is observed depending on assay conditions) and its kinetic mechanism
      (ping-pong) supports the structure-derived prediction that PP i dissociation must
      precede the switch from conformation 1 to conformation 2 and therefore CoA
      binding. Also, transient kinetic analysis of wild-type CBL identified the rate
      limiting step of the catalyzed reaction as one that follows the formation of 4-CB
      CoA (viz. CBL conformational change and/or product dissociation). The single
      turnover rate of 4-CB and ATP to form 4-CB-AMP and PP i ( k = 300 s (-1)) is not
      affected by the presence of CoA, and it is approximately 3-fold faster than the
      turnover rate of 4-CB-AMP and CoA to form 4-CB-CoA and AMP ( k = 120 s (-1)).
      Second, the active site mutants screened via steady-state kinetic analysis were
      ranked based on the degree of reduction observed in any one of the substrate k
      cat/ K m values, and those scoring higher than a 50-fold reduction in k cat/ K m
      value were selected for further evaluation via transient state kinetic analysis.
      The single-turnover time courses, measured for the first partial reaction, and
      then for the full reaction, were analyzed to define the microscopic rate
      constants for the adenylation reaction and the thioesterification reaction. On
      the basis of our findings we propose a catalytic mechanism that centers on a
      small group of key residues (some of which serve in more than one role) and that
      includes several residues that function in domain alternation.

PMID- 18620422
TI  - Roles of K+, H+, H2O, and DeltaPsi in solute transport mediated by major
      facilitator superfamily members ProP and LacY.
AB  - H (+)-solute symporters ProP and LacY are members of the major facilitator
      superfamily. ProP mediates osmoprotectant (e.g., proline) accumulation, whereas
      LacY transports the nutrient lactose. The roles of K (+), H (+), H 2O, and
      DeltaPsi in H (+)-proline and H (+)-lactose symport were compared using right
      side-out cytoplasmic membrane vesicles (MVs) from bacteria expressing both
      transporters and proteoliposomes (PRLs) reconstituted with pure ProP-His 6. ProP
      activity increased as LacY activity decreased when osmotic stress (increasing
      osmolality) was imposed on MVs. The activities of both transporters decreased to
      similar extents when Na (+) replaced K (+) in MV preparations. Thus, K (+) did
      not specifically control ProP activity. As with LacY, an increasing
      extravesicular pH stimulated ProP-mediated proline efflux much more than ProP
      mediated proline exchange from de-energized MVs. In contrast to that of LacY,
      ProP-mediated exchange was only 2-fold faster than ProP-mediated efflux and was
      inhibited by respiration. In the absence of the protonmotive force (Deltamu H (+)
      ), efflux of lactose from MVs was much more sensitive to increasing osmolality
      than lactose exchange. Thus, H 2O may be directly involved in proton transport
      via LacY. In the absence of Deltamu H (+) , proline efflux and exchange from MVs
      were osmolality-independent. In PRLs with a DeltapH of 1 (lumen alkaline), ProP
      His 6 was inactive when the membrane potential (DeltaPsi) was zero, was active
      but insensitive to osmolality when DeltaPsi was -100 mV, and became osmolality
      sensitive as DeltaPsi increased further to -137 mV. ProP-His 6 had the same
      membrane orientation in PRLs as in cells and MVs. ProP switches among "off",
      "on", and "osmolality-sensitive" states as the membrane potential increases.
      Kinetic parameters determined in the absence of Deltamu H (+) represent a ProP
      population that is predominantly off.

PMID- 18620424
TI  - A metabolic bypass of the triosephosphate isomerase reaction.
AB  - Triosephosphate isomerase (TIM) catalyzes the interconversion of d-glyceraldehyde
      3-phosphate and dihydroxyacetone phosphate, an essential step in glycolytic and
      gluconeogenic metabolism. To uncover promiscuous isomerases embedded within the
      Escherichia coli genome, we searched for genes capable of restoring growth of a
      TIM-deficient bacterium under gluconeogenic conditions. Rather than discovering
      an isomerase, we selected yghZ, a gene encoding a member of the aldo-keto
      reductase superfamily. Here we show that YghZ catalyzes the stereospecific, NADPH
      dependent reduction of l-glyceraldehyde 3-phosphate, the enantiomer of the TIM
      substrate. This transformation provides an alternate pathway to the formation of
      dihydroxyacetone phosphate.

PMID- 18620425
TI  - Tetrameric bacterial sodium channels: characterization of structure, stability,
      and drug binding.
AB  - NaChBac from Bacillus halodurans is a bacterial homologue of mammalian voltage
      gated sodium channels. It has been proposed that a NaChBac monomer corresponds to
      a single domain of the mammalian sodium channel and that, like potassium
      channels, four monomers form a tetrameric channel. However, to date, although
      NaChBac has been well-characterized for functional properties by
      electrophysiological measurements on protein expressed in tissue culture, little
      information about its structural properties exists because of the difficulties in
      expressing the protein in large quantities. In this study, we present studies on
      the overexpression of NaChBac in Escherichia coli, purification of the functional
      detergent-solubilized channel, its identification as a tetramer, and
      characterization of its secondary structure, drug binding, and thermal stability.
      These studies are correlated with a model produced for the protein and provide
      new insights into the structure-function relationships of this sodium channel.

PMID- 18620427
TI  - Amino-modified diamond as a durable stationary phase for solid-phase extraction.
AB  - We report the formation of a highly stable amino stationary phase on diamond and
      demonstrate its use in solid-phase extraction (SPE). This process consists of
      spontaneous and self-limiting adsorption of polyallylamine (PAAm) from aqueous
      solution onto oxidized diamond. Thermal curing under reduced pressure or chemical
      cross-linking with a diepoxide was shown to fix the polymer to the particles. The
      resulting adsorbents are stable under even extreme pH conditions (from at least
      pH 0-14) and significantly more stable than a commercially available amino SPE
      adsorbent. Coated diamond particles were characterized by X-ray photoelectron
      spectroscopy (XPS) and diffuse reflectance Fourier transform-infrared
      spectroscopy (DRIFT). Model silicon surfaces were characterized by spectroscopic
      ellipsometry and wetting. Solid-phase extraction was demonstrated using
      cholesterol, hexadecanedioic acid, and palmitoyloleoylphosphatidylcholine as
      analytes, and these results were compared to those obtained with commercially
      available materials. Breakthrough curves indicate that, as expected, porous
      diamond particles have higher analyte capacity than nonporous solid particles.

PMID- 18620426
TI  - Mass-balanced 1H/2H isotope dipeptide tag for simultaneous protein quantitation
      and identification.
AB  - Mass-balanced (1)H/(2)H isotope dipeptide tags (MBITs) are presented for
      simultaneous protein quantitation and identification. MBIT is derived from N
      acetyl-Ala-Ala dipeptide and conjugated to primary amines of target peptides.
      (1)H/(2)H isotopes are encoded in the methyl groups of N-acetylated dipeptide:
      one tag deuterated on the N-acetyl group and another on the C-terminal alanine.
      MBIT-linked peptides comigrate in reversed-phase liquid chromatography without
      significant (1)H/(2)H isotope effects and provide 2-plex quantitation signals at
      114 and 117 Th as well as peptide sequence information upon MS/MS analysis with
      MALDI TOF/TOF. MBIT shows good quantitation linearity in a concentration range of
      20-250 fmol. The performance of MBIT on protein quantitation and identification
      is further tested with yeast heat-shock protein (Hsp82p) obtained from three
      different physiological states. MBIT using nanogram-scale samples produces the
      relative abundance ratios comparable to those obtained from optical imaging of
      microgram-scale samples visualized with SYPRO Ruby stain. The MBIT strategy is a
      simple and low-cost alternative for 2-plex quantitation of proteins and offers
      possibilities of tuning the 2-plex signal mass window by replacing the N-terminal
      alanine with other amino acid residues.

PMID- 18620428
TI  - Synchronized, continuous-flow zone electrophoresis.
AB  - A new method for performing continuous electrophoretic separation of complex
      mixtures in microscale devices is proposed. Unlike in free-flow electrophoresis
      devices, no mechanical pumping is required--both fluid transport and separation
      are driven electrokinetically. This gives the method great potential for on-a
      chip integration in multistep analytical systems. The method enables us to
      collect fractionated sample and tenfold purification is possible. The model of
      the operation is presented and a detailed description of the optimal conditions
      for performing purification is given. The chip devices with 10-microm-deep
      separation chamber of 1.5 mm x 4 mm in size were fabricated in glass. A standard
      microchip electrophoresis setup was used. Continuous separation of rhodamine B,
      rhodamine 6G, and fluorescein was accomplished. Purification was demonstrated on
      a mixture containing rhodamine B and fluorescein, and the recovery of both
      fractions was achieved. The results show the feasibility of the method.

PMID- 18620429
TI  - Estimation of atmospheric lifetimes of hydrofluorocarbons, hydrofluoroethers, and
      olefins by chlorine photolysis using gas-phase NMR spectroscopy.
AB  - An empirical correlation has been derived between accepted atmospheric lifetimes
      of a set of hydrofluorocarbons and hydrofluoroethers and relative rates of
      reaction with photolyzed chlorine in excess at ambient temperature. These kinetic
      systems were studied by nuclear magnetic resonance (NMR) spectroscopy in the gas
      phase, marking the first application of NMR spectroscopy to this field. The
      square of the Pearson coefficient R for the linear correlation between observed
      reaction rates and accepted atmospheric lifetimes was 0.87 for compounds of
      lifetime less than 20 years. The method was extended to the study of ethene and
      propene; the rate of reaction of propene was found to be 1.25 times that of
      ethene at 23 degrees C. The chief advantage of this method is its simplicity and
      reliance only on common tools and techniques of an industrial chemical
      laboratory.

PMID- 18620430
TI  - Towards nanoscale molecular analysis at atmospheric pressure by a near-field
      laser ablation ion trap/time-of-flight mass spectrometer.
AB  - An instrument that combines near-field laser ablation at atmospheric pressure
      with an ion trap/time-of-flight mass spectrometer was developed. By coupling a UV
      laser into a fiber tip of a scanning near-field optical microscope, ablation
      craters much smaller than achievable with conventional laser optics can in
      principle be obtained. Laser ablation was performed on samples such as DHB,
      anthracene, and pyrene. Desorbed neutral analytes are transferred from
      atmospheric pressure to an ion trap, ionized, and stored. After 10 ms, the ions
      are extracted into a sensitive time-of-flight spectrometer. We demonstrate the
      feasibility of this unique SNOM-MS instrument for chemical analysis with
      unprecedented lateral resolution at atmospheric pressure. Spatially resolved
      molecular analysis with a lateral resolution of 5 microm (fwhm) and a sensitivity
      of approximately 60 fmol of solid anthracene is demonstrated, along with
      topographical analysis with the same instrument. No other technique available
      today offers this lateral resolution in combination with soft mass spectrometry
      and the capability of sampling fragile specimens at atmospheric pressure.

PMID- 18620431
TI  - Development of air-stable, supported membrane arrays with photolithography for
      study of phosphoinositide-protein interactions using surface plasmon resonance
      imaging.
AB  - We report the development of an air-stable, supported membrane array by use of
      photolithography for label-free detection of lipid-protein interactions.
      Phosphoinositides and their phosphorylated derivatives (PIPs) were studied for
      their binding properties to proteins with lipid microarray in combination with
      surface plasmon resonance imaging (SPRi). We have demonstrated a simple method to
      fabricate lipid arrays using photoresist and carried out a series of surface
      characterizations with SPRi, ac impedance, cyclic voltammetry, and fluorescence
      microscopy to validate the array quality and lipid bilayer formation. A number of
      lipid compositions have been tested for the robustness of resulting membranes
      when undergoing dehydration and rehydration procedures, and the 1,2-dioleoyl-sn
      glycero-3-ethylphosphocholine/poly(ethylene glycol)-phosphatidylethanolamine
      (DOPC+/PEG-PE) system stands out as the best performer that yields the recovery
      to within 2% of the original state according to SPR sensorgrams. Limits of
      detection on the dehydrated/rehydrated DOPC+/PEG-PE membranes were determined to
      be 33 nM for avidin binding to biotinylated lipids, 73.5 nM for cholera toxin to
      GM1, and 25 nM for PtdIns(4,5)P2-binding protein (P(4,5)BP) to PtdIns(4,5)P2
      lipid, respectively. These results demonstrate the suitability and sensitivity of
      this membrane for constructing membrane arrays for SPRi analysis under ambient
      conditions. With the use of this addressable and functional lipid membrane array,
      the screening of specific lipid-protein interactions has been conducted. Strong
      and specific interactions between P(4,5)BP and PtdIns(4,5)P2/DOPC+/PEG-PE
      membrane were observed as expected, while cross reactions were spotted for
      P(4,5)BP/PtdIns(4)P and avidin/GM1 at varied degrees. The air-stable membrane
      array demonstrated here presents a simple, effective approach for constructing
      functional membrane surfaces for screening applications, which opens a new avenue
      for the label-free study of membrane proteins and other forms of lipid-membrane
      interactions.

PMID- 18620432
TI  - Flavonoids as substrates and inhibitors of myeloperoxidase: molecular actions of
      aglycone and metabolites.
AB  - Myeloperoxidase (MPO), secreted by activated neutrophils and macrophages at the
      site of inflammation, may be implicated in the oxidation of protein/lipoprotein
      during the development of cardiovascular diseases. Flavonoids have been suggested
      to act as antioxidative and anti-inflammatory agents in vivo; however, their
      molecular actions have not yet been fully understood. In this study, we examined
      the molecular basis of the inhibitory effects of dietary flavonoids, such as
      quercetin, and their metabolites on the catalytic reaction of MPO using a
      combination of biological assays and theoretical calculation studies.
      Immunohistochemical staining showed that a quercetin metabolite was colocalized
      with macrophages, MPO, and dityrosine, an MPO-derived oxidation product of
      tyrosine, in human atherosclerotic aorta. Quercetin and the plasma metabolites
      inhibited the formation of dityrosine catalyzed by the MPO enzyme and HL-60 cells
      in a dose-dependent manner. Spectrometric analysis indicated that quercetin might
      act as a cosubstrate of MPO resulting in the formation of the oxidized quercetin.
      Quantitative structure-activity relationship studies showed that the inhibitory
      actions of flavonoids strongly depended not only on radical scavenging activity
      but also on hydrophobicity (log P). The requirement of a set of hydroxyl groups
      at the 3, 5, and 4'-positions and C2-C3 double bond was suggested for the
      inhibitory effect. The binding of quercetin and the metabolites to a hydrophobic
      region at the entrance to the distal heme pocket of MPO was also proposed by a
      computer docking simulation. The current study provides the structure-activity
      relationships for flavonoids as the anti-inflammatory dietary constituents
      targeting the MPO-derived oxidative reactions in vivo.

PMID- 18620435
TI  - Surface charge microscopy: novel technique for mapping charge-mosaic surfaces in
      electrolyte solutions.
AB  - The effective surface potential, called the zeta potential, is commonly
      determined from electrophoretic mobility measurements for particles moving in a
      solution in response to an electric field applied between two electrodes. The
      situation can be reversed, with the solution being forced to flow through a plug
      of packed particles, and the streaming potential of the particles can be
      calculated. A significant limitation of these electrokinetic measurements is that
      only an average value of the zeta potential/streaming potential is measured-
      regardless of whether the surface charge distribution is homogeneous or
      otherwise. However, in real-world situations, nearly all solids (and liquids) of
      technological significance exhibit surface heterogeneities. To detect
      heterogeneities in surface charge, analytical tools which provide accurate and
      spatially resolved information about the material surface potential--particularly
      at microscopic and submicroscopic resolutions--are needed. In this study, atomic
      force microscopy (AFM) was used to measure the surface interaction forces between
      a silicon nitride AFM cantilever and a multiphase volcanic rock. The experiments
      were conducted in electrolyte solutions with different ionic strengths and pH
      values. The colloidal force measurements were carried out stepwise across the
      boundary between adjacent phases. At each location, the force-distance curves
      were recorded. Surface charge densities were then calculated by fitting the
      experimental data with a DLVO theoretical model. Significant differences between
      the surface charge densities of the two phases and gradual transitions in the
      surface charge density at the interface were observed. It is demonstrated that
      this novel technique can be applied to examine one- and two-dimensional
      distributions of the surface potential.

PMID- 18620434
TI  - Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions employing
      dialkylbiaryl phosphine ligands.
AB  - The cores of many types of polymers, ligands, natural products, and
      pharmaceuticals contain biaryl or substituted aromatic structures, and efficient
      methods of synthesizing these structures are crucial to the work of a broad
      spectrum of organic chemists. Recently, Pd-catalyzed carbon-carbon bond-forming
      processes, particularly the Suzuki-Miyaura cross-coupling reaction (SMC), have
      risen in popularity for this purpose. The SMC has many advantages over other
      methods for constructing these moieties, including mild conditions, high
      tolerance toward functional groups, the commercial availability and stability of
      its reagents, and the ease of handling and separating byproducts from its
      reaction mixtures. Until 1998, most catalysts for the SMC employed
      triarylphosphine ligands. More recently, new bulky and electron-rich phosphine
      ligands, which can dramatically improve the efficiency and selectivity of such
      cross-coupling reactions, have been introduced. In the course of our studies on
      carbon-nitrogen bond-forming reactions, we found that the use of electron-rich
      and bulky phosphines enhanced the rate of both the oxidative addition and
      reductive elimination processes; this was the beginning of our development of a
      new family of ligands, the dialkylbiarylphosphines L1-L12. These ligands can be
      used for a wide variety of palladium-catalyzed carbon-carbon, carbon-nitrogen,
      and carbon-oxygen bond-forming processes as well as serving as supporting ligands
      for a number of other reactions. The enhanced reactivity of these catalysts has
      expanded the scope of cross-coupling partners that can be employed in the SMC.
      With use of such dialkylbiarylphosphine ligands, the coupling of unactivated aryl
      chlorides, aryl tosylates, heteroaryl systems, and very hindered substrate
      combinations have become routine. The utility of these ligands has been
      successfully demonstrated in a wide number of synthetic applications, including
      industrially relevant processes. In this Account, we provide an overview of the
      use and impact of dialkylbiarylphosphine ligands in the SMC. We discuss our
      studies on the mechanistic framework of the reaction, which have allowed us to
      rationally modify the ligand structures in order to tune their properties. We
      also describe selected applications in the synthesis of natural products and new
      materials to illustrate the utility of these dialkylbiarylphosphine ligands in
      various "real-world" synthetic applications.

PMID- 18620436
TI  - One-step photochemical attachment of NHS-terminated monolayers onto silicon
      surfaces and subsequent functionalization.
AB  - N-Hydroxysuccinimide (NHS)-ester-terminated monolayers were covalently attached
      in one step onto silicon using visible light. This mild photochemical attachment,
      starting from omega-NHS-functionalized 1-alkenes, yields a clean and flat
      monolayer-modified silicon surface and allows a mild and rapid functionalization
      of the surface by substitution of the NHS-ester moieties with amines at room
      temperature. Using a combination of analytical techniques (infrared reflection
      absorption spectroscopy (IRRAS), extensive X-ray photoelectron spectroscopy (XPS)
      in combination with density functional theory calculations of the XPS chemical
      shifts of the carbon atoms, atomic force microscopy (AFM), and static contact
      angle measurements), it was shown that the NHS-ester groups were attached fully
      intact onto the surface. The surface reactivity of the NHS-ester moieties toward
      amines was qualitatively and quantitatively evaluated via the reaction with para
      trifluoromethyl benzylamine and biotin hydrazide.

PMID- 18620437
TI  - Preparation, characterization, and chemical stability of gold nanoparticles
      coated with mono-, bis-, and tris-chelating alkanethiols.
AB  - A systematically varying series of monolayer-protected clusters (MPCs) was
      prepared by exposing small gold nanoparticles ( approximately 2 nm in diameter)
      to the following four adsorbates: n-octadecanethiol ( n - C18), 2
      hexadecylpropane-1,3-dithiol ( C18C2), 2-hexadecyl-2-methylpropane-1,3-dithiol (
      C18C3), and 1,1,1-tris(mercaptomethyl)heptadecane ( t - C18). The resultant MPCs
      were characterized by solubility studies, UV-vis spectroscopy, transmission
      electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier
      transform infrared spectroscopy (FT-IR). All of the MPCs were soluble in common
      organic solvents; moreover, analysis by TEM showed that the core dimensions were
      unaffected by exposure to any of the adsorbates. Separate studies by XPS revealed
      that the sulfur atoms in all MPCs were predominantly bound to the surface of gold
      (i.e., approximately 85% or better). Analysis by FT-IR showed that MPCs
      functionalized with n - C18 possessed alkyl chains having the greatest
      conformational order in both the solid-state and dispersed in solution; in
      contrast, those generated from the other three adsorbates were more liquid-like
      with reduced conformational order (or crystallinity). The rate of nanoparticle
      decomposition induced by cyanide ions was monitored by UV-vis spectroscopy. While
      MPCs functionalized with n - C18 showed the fastest rate of decomposition, those
      functionalized with C18C3 were the most resistant to decomposition. Overall, the
      following trend in chemical stability was observed, C18C3 >> C18C2 > t - C18 >> n
      - C18.

PMID- 18620438
TI  - Influence of nanoparticle addition on the properties of wormlike micellar
      solutions.
AB  - The addition of positively charged, 30 nm diameter silica nanoparticles to
      cationic wormlike micellar solutions of cetyltrimethylammonium bromide and sodium
      nitrate is studied using a combination of rheology, small angle neutron
      scattering, dynamic light scattering, and cryo-transmission electron microscopy.
      The mixtures are single phase up to particle volume fractions of 1%. The addition
      of like-charged particles significantly increases the wormlike micelle (WLM)
      solution's zero shear rate viscosity, longest relaxation time, and storage
      modulus. The changes are hypothesized to originate from a close association of
      the particles with the micellar mesh. Small angle neutron scattering measurements
      with contrast matching demonstrate associations between particles mitigated by
      the WLMs. The effective interparticle interactions measured by SANS can explain
      the observed phase behavior. Dynamic light scattering measurements confirm the
      dynamic coupling of the particles to the micellar mesh.

PMID- 18620439
TI  - Role of nanomechanical properties in the tribological performance of phospholipid
      biomimetic surfaces.
AB  - The role of phospholipid bilayers in controlling and reducing frictional forces
      between biological surfaces is investigated by three complementary experiments:
      friction forces are measured using a homemade tribometer, mechanical resistance
      to indentation is measured by AFM, and lipid bilayer degradation is controlled in
      situ during friction testing using fluorescence microscopy. DPPC lipid bilayers
      in the solid phase generate friction coefficients as low as 0.002 (comparable to
      that found for cartilage) that are stable through time. DOPC bilayers formed by
      the vesicle fusion method or the adsorption of mixed micelles generate higher
      friction coefficients. These coefficients increased through time, during which
      the bilayers degraded. The friction coefficient is correlated with the force
      needed to penetrate the bilayer with the AFM tip. With only one bilayer in the
      contact region, the friction increased to a similar value of about 0.08 for the
      DPPC and DOPC. Our study therefore shows that good mechanical stability of the
      bilayers is essential and suggests that the low friction coefficient is ensured
      by the hydration layers between adjacent lipid bilayers.

PMID- 18620440
TI  - Transport and separation of charged macromolecules under nonlinear
      electromigration in nanochannels.
AB  - In this work, we theoretically investigate the implications of nonlinear
      electrophoretic effects on the transport and size-based separation of charged
      macromolecules in nanoscale confinements. By employing a regular perturbation
      analysis, we address certain nontrivial features of interconnection among wall
      induced transverse migrative fluxes, electrophoretic and electroosmotic
      transport, confinement-induced hindered diffusive effects, and hydrodynamic
      interactions in detail. We demonstrate that there occurs an optimal regime of
      influence of the nonlinear electrophoretic effects, within which high values of
      separation resolution may be achieved. This size-based optimal regime, however,
      can be effectively exploited only for nanochannel flows, as attributed to the
      strong electric double layer interactions prevalent within the same.

PMID- 18620441
TI  - Predictive modeling of electrocatalyst structure based on structure-to-property
      correlations of x-ray photoelectron spectroscopic and electrochemical
      measurements.
AB  - Chemical structure and catalytic activity of nonplatinum porphyrin-based
      electrocatalyst for oxygen reduction is characterized by combination of X-ray
      photoelectron spectroscopy (XPS) and rotating disk electrode. The goal of the
      study is to show how modifications in the molecular structure affect catalytic
      characteristics and how to use these structural modifications in a purposeful
      manner to increase catalytic activity. Initial correlation of structure to
      electrochemical performance is achieved through the application of principal
      component analysis (PCA) to curve-fits of high-resolution XPS spectra combined
      with results of electrochemical measurements. Furthermore, a predictive model
      that describes this correlation is build using the combination of genetic
      algorithm (GA) and multiple linear regression (MLR). Based on structure-to
      property correlations, two types of active sites responsible for the catalytic
      activity, i.e., Co associated with pyropolymer and Co particles covered by oxide
      layer, are determined, and a dual-site for oxygen reduction on cobalt porphyrins
      is hypothesized, allowing for designing a catalyst structure with optimal
      performance characteristics.

PMID- 18620442
TI  - Transport processes in responding lipid membranes: a possible mechanism for the
      pH gradient in the stratum corneum.
AB  - The "acidic mantle" of the skin surface has been related to several essential
      functions of the skin, although the origin of the acidity is still obscure. In
      this paper, we investigate how different transport processes can influence the
      local proton concentration inside a membrane consisting of oriented lipid
      bilayers. This system is chosen as a simple model of the extracellular lipids in
      the upper layer of the skin, the stratum corneum. We present a theoretical model
      for diffusional transport over the membrane in the presence of an osmotic
      gradient and a gradient in CO(2), taking into account the influence of these
      gradients on the lipid structure and the local electrostatics. We are also
      discussing the complications in applying the concept of pH to the stratum
      corneum. From this, we make the following conclusions: (i) The definition of pH
      in the stratum corneum is ambiguous, and thus, all statements regarding pH should
      always be related to a clear definition. (ii) A natural definition of pH in the
      stratum corneum can be proposed which takes into account local heterogeneity,
      local charges, and the fact that the stratum corneum is not in thermodynamical
      equilibrium. (iii) Diffusive transport across an oriented bilayer stack in the
      presence of an osmotic gradient and/or a gradient in CO(2) can give rise to a
      substantial gradient in pH. (iv) The results from the simplified model can be
      correlated to experimental observations of pH in the stratum corneum.

PMID- 18620443
TI  - Transmission X-ray microscopy (TXM) reveals the nanostructure of a smectite gel.
AB  - The unusual behavior of smectites, the ability to change volume when wetted
      (swelling) or dried (shrinking), makes soil rich in smectites very unstable and
      dangerous for the building industry because of the movement of building
      foundations and poor slope stability. These macroscopic properties are dominated
      by the structural arrangement of the smectites' finest fraction. Here, we show in
      three dimensions how the swelling phenomenon in smectite, caused by a combination
      of hydratation and electrostatic forces, may expand the dry smectite volume not
      10-fold, as previously thought, but to more than 1000-fold. A new technique,
      transmission X-ray microscopy, makes it possible to investigate the internal
      structure and 3-D tomographic reconstruction of clay aggregates. This reveals,
      for the first time, the smectite gel arrangement in the voluminous cellular
      tactoid structure within a natural aqueous environment.

PMID- 18620444
TI  - Reversible pH-triggered encapsulation and release of pyrene by adsorbed block
      copolymer micelles.
AB  - The well-established ability of copolymer micelles to encapsulate and release
      hydrophobic molecules has been investigated following their adsorption onto
      silica particles. Here, a pH-responsive copolymer, poly(2-(dimethylamino)ethyl
      methacrylate)- b-poly(2-(diethylamino)ethyl methacrylate) (PDMA(106)- b
      PDEA(25)), has been used to study the formation and dissociation of adsorbed
      micelles through pH variation. This copolymer behaves as free unimers in aqueous
      solutions below pH 8 and forms micelles 29 nm in hydrodynamic diameter above this
      pH. Encapsulation and release of a model hydrophobic compound (pyrene) by in situ
      adjustment of the solution pH has been compared for both free and adsorbed
      micelles using fluorescence spectrophotometry, epifluorescence microscopy, and
      zeta potential measurements. At basic pH values, pyrene is solubilized within the
      cores of micelles adsorbed on silica particles: addition of acid leads to micelle
      dissociation and release of the pyrene into the bulk aqueous solution. Micelle
      adsorption does not appear to hinder the extent of pyrene uptake/release.
      Moreover, this pH-responsive behavior is both reversible and reproducible over
      multiple pH cycles.

PMID- 18620445
TI  - Lateral structures of buried interfaces in ABA-type triblock copolymer films.
AB  - The lateral structure of an ABA-type triblock copolymer polyparamethylstyrene-
      block-polystyrene- block-polyparamethylstyrene at the buried silicon substrate
      interface is studied as a function of different substrate surface treatments.
      With grazing incidence small-angle neutron scattering (GISANS), high interface
      sensitivity is reached. With GISANS, the orientation and degree of order of the
      morphology are probed. The powderlike oriented lamellar structure in the bulk
      orients along the surface normal in the vicinity of the substrate. A modification
      of the short-ranged interface potential of the substrate introduces a lateral
      stretching of this lamellar structure of up to 8% as compared to the bulk. The
      decay in stretching toward the volume structure is probed with depth profiling.
      It extends at least up to a distance of 51 nm from the solid surface.

PMID- 18620446
TI  - A beta-cyclodextrin "click cluster" decorated with seven paramagnetic chelates
      containing two water exchange sites.
AB  - The development of novel macromolecular contrast agents that offer enhanced
      relaxivity profiles at high magnetic fields have the potential to greatly improve
      the diagnosis, understanding, and treatment of disease. To this end, we have
      designed a monodiperse paramagnetic beta-cyclodextrin click cluster decorated
      with seven paramagnetic arms. A novel alkyne-functionalized
      diethylenetriaminetetraacetic acid (DTTA) chelate (6) has been created and
      coupled to a per-azido-beta-cyclodextrin core (7) to yield the precursor
      macromolecule (8). After removal of the protecting groups and titrating with Gd
      (3+), the final paramagnetic click cluster, Gd10, was obtained. Luminescence
      measurements were carried out in H 2O and D 2O on an analogous structure, Eu10,
      and indicated that at each lanthanide has an average of 1.8 water exchange sites,
      which is important for enhancing relaxivity and MRI resolution. This discrete
      paramagnetic click cluster yields a high relaxivity profile (43.4 mM (-1) s (-1)
      per molecule and 6.2 mM (-1) s (-1) per Gd (3+) at 9.4 T) and enhanced contrast
      on a human MRI scanner as compared to a commercial agent, Magnevist (3.2 mM (-1)
      s (-1) at 9.4 T). Moreover, the useful inclusion properties exhibited by beta
      cyclodextrin also make this an excellent host scaffold to functionalize via
      noncovalent assembly with receptor specific targeting moieties for biomolecular
      imaging.

PMID- 18620448
TI  - Prediction of acute cellular renal allograft rejection by urinary metabolomics
      using MALDI-FTMS.
AB  - The present study investigated small molecule analysis of urinary samples as a
      noninvasive method to detect acute cellular renal allograft rejection. Matrix
      assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI
      FTMS) was used to analyze 15 urinary samples from transplant patients with
      different grades of biopsy showing improved clinical acute cellular rejection
      (ACR) and 24 urinary samples from 8 transplant patients without evidence of
      rejection. Seven small molecules demonstrated highly successful diagnostic
      performance (m/z): 278.1 (t = 3.398, p = 0.004), 293.0 (t = 2.169, p = 0.048),
      294.1 (t = 2.154, p = 0.05), 382.2 (t = 2.961, p = 0.010), 383.3 (t = 2.270, p =
      0.040), 402.2 (t = 2.994, p = 0.010), 424.0 (t = 2.644, p = 0.019). Kidney
      transplant patients with ACR could be distinguished from those without ACR using
      four individual small molecules with a specificity of 100%. In conclusion, the
      combination of MALDI-FTMS technology with a clear definition of patient groups
      can detect urine small molecule associated with ACR.

PMID- 18620449
TI  - Proteomics of multigenic families from species underrepresented in databases: the
      case of loquat (Eriobotrya japonica Lindl.) polyphenol oxidases.
AB  - Here, we approach the problem of obtaining accurate and reliable information
      about the gene origin of a protein belonging to a multigenic family, polyphenol
      oxidase, from an underrepresented species, Eriobotrya japonica. De novo
      sequencing was a key approach to obtain broad sequence coverage. Alignment of
      peptides on their most similar homologous protein revealed divergent amino acid
      positions that lead to hypothesize the minimal number of genes encoding for the
      proteins analyzed.

PMID- 18620447
TI  - Evaluation of a maleimido derivative of CHX-A'' DTPA for site-specific labeling
      of affibody molecules.
AB  - Affibody molecules are a new class of small targeting proteins based on a common
      three-helix bundle structure. Affibody molecules binding a desired target may be
      selected using phage-display technology. An Affibody molecule Z HER2:342 binding
      with subnanomolar affinity to the tumor antigen HER2 has recently been developed
      for radionuclide imaging in vivo. Introduction of a single cysteine into the
      cysteine-free Affibody scaffold provides a unique thiol group for site-specific
      labeling of recombinant Affibody molecules. The recently developed maleimido-CHX
      A'' DTPA was site-specifically conjugated at the C-terminal cysteine of Z
      HER2:2395-C, a variant of Z HER2:342, providing a homogeneous conjugate with a
      dissociation constant of 56 pM. The yield of labeling with (111)In was >99% after
      10 min at room temperature. In vitro cell tests demonstrated specific binding of
      (111)In-CHX-A'' DTPA-Z 2395-C to HER2-expressing cell-line SKOV-3 and good
      cellular retention of radioactivity. In normal mice, the conjugate demonstrated
      rapid clearance from all nonspecific organs except kidney. In mice bearing SKOV-3
      xenografts, the tumor uptake of (111)In-CHX-A'' DTPA-Z 2395-C was 17.3 +/- 4.8%
      IA/g and the tumor-to-blood ratio 86 +/- 46 (4 h postinjection). HER2-expressing
      xenografts were clearly visualized 1 h postinjection. In conclusion, coupling of
      maleimido-CHX-A'' DTPA to cysteine-containing Affibody molecules provides a well
      defined uniform conjugate, which can be rapidly labeled at room temperature and
      provides high-contrast imaging of molecular targets in vivo.

PMID- 18620452
TI  - Conformation of poly(styrene sulfonate) layers physisorbed from high salt
      solution studied by force measurements on two different length scales.
AB  - The conformation of poly(styrene sulfonate) (PSS) layers physisorbed from 1 M
      NaCl is determined by force measurements and imaging on two length scales. With
      colloidal probe technique steric forces as predicted for neutral grafted brushes
      are observed. On decrease and increase of the NaCl concentration, the grafting
      density remains constant, yet the brush thickness swells and shrinks reversibly
      with the salt concentration with an exponent of -0.3. At low salt conditions, the
      brush length amounts to 30% of the contour length, a behavior known for
      polyelectrolyte brushes and attributed to the entropy of the counterions trapped
      in the brush. Between a PSS layer and a pure colloidal silica sphere, the same
      steric forces are observed, and additionally at large separations (beyond the
      range of the steric repulsion) an electrostatic force is found. A negatively
      charged AFM tip penetrates the brush--a repulsive electrostatic force between the
      tip and surface is found, and single chains can be imaged. Thus, with the
      nanometer-sized AFM tip, the flatly adsorbed fraction of the PSS chains is seen,
      whereas the micrometer-sized colloidal probe interacts with the fraction of the
      chains penetrating into solution.

PMID- 18620451
TI  - Poly(amidoamine) dendrimers on lipid bilayers II: Effects of bilayer phase and
      dendrimer termination.
AB  - The molecular structures and enthalpy release of poly(amidoamine) (PAMAM)
      dendrimers binding to 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC)
      bilayers were explored through atomistic molecular dynamics. Three PAMAM
      dendrimer terminations were examined: protonated primary amine, neutral
      acetamide, and deprotonated carboxylic acid. Fluid and gel lipid phases were
      examined to extract the effects of lipid tail mobility on the binding of
      generation-3 dendrimers, which are directly relevant to the nanoparticle
      interactions involving lipid rafts, endocytosis, lipid removal, and/or membrane
      pores. Upon binding to gel phase lipids, dendrimers remained spherical, had a
      constant radius of gyration, and approximately one-quarter of the terminal groups
      were in close proximity to the lipids. In contrast, upon binding to fluid phase
      bilayers, dendrimers flattened out with a large increase in their asphericity and
      radii of gyration. Although over twice as many dendrimer-lipid contacts were
      formed on fluid versus gel phase lipids, the dendrimer-lipid interaction energy
      was only 20% stronger. The greatest enthalpy release upon binding was between the
      charged dendrimers and the lipid bilayer. However, the stronger binding to fluid
      versus gel phase lipids was driven by the hydrophobic interactions between the
      inner dendrimer and lipid tails.

PMID- 18620450
TI  - Poly(amidoamine) dendrimers on lipid bilayers I: Free energy and conformation of
      binding.
AB  - Third-generation (G3) poly(amidoamine) (PAMAM) dendrimers are simulated
      approaching 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) bilayers with
      fully atomistic molecular dynamics, which enables the calculation of a free
      energy profile along the approach coordinate. Three different dendrimer
      terminations are examined: protonated primary amine, uncharged acetamide, and
      deprotonated carboxylic acid. As the dendrimer and lipids become closer, their
      attractive force increases (up to 240 pN) and the dendrimer becomes deformed as
      it interacts with the lipids. The total energy release upon binding of a G3-NH3+,
      G3-Ac, or G3-COO- dendrimer to a DMPC bilayer is, respectively, 36, 26, or 47
      kcal/mol or, equivalently, 5.2, 3.2, or 4.7x10(-3) kcal/g. These results are
      analyzed in terms of the dendrimers' size, shape, and atomic distributions as
      well as proximity of individual lipid molecules and particular lipid atoms to the
      dendrimer. For example, an area of 9.6, 8.2, or 7.9 nm2 is covered on the bilayer
      for the G3-NH3+, G3-Ac, or G3-COO- dendrimers, respectively, while interacting
      strongly with 18-13 individual lipid molecules.

PMID- 18620453
TI  - Aqueous laponite clay dispersions in the presence of poly(ethylene oxide) or
      poly(propylene oxide) oligomers and their triblock copolymers.
AB  - The effect of polyethylene oxide (PEO) or polypropylene oxide (PPO) oligomers of
      various molecular weight (Mw) as well as of triblock copolymers, based on PEO and
      PPO blocks, on aqueous laponite RD suspensions was studied with small-angle
      neutron scattering (SANS). The radius of gyration (RG) increases for low M w
      whereas the opposite occurs for larger Mw. This behavior is explained on the
      basis that an effective R G is given by two contributions: (1) the size of the
      particles coated with the polymer and (2) the interactions between the laponite
      RD particles which are attractive for small and repulsive for large polymers. The
      SANS curves in the whole Q-range are well described by a model of noninteracting
      polydisperse core+shell disks, where the thickness of the polymer layer increases
      with the Mw. The adsorbed polymer is in a more compact conformation compared to a
      random coil distribution while the fraction of the polymer in the shell formed
      around the laponite RD particles is nearly independent of Mw. For increasing
      laponite RD amounts, at a given polymer composition, the thickness of the polymer
      slightly changes. In some cases, where also gelation is sped up, a structure
      factor with attractive interaction was employed which allowed to evaluate the
      attractive forces between the laponite RD particles. The gelation time was
      determined for mixtures at fixed copolymer and laponite RD concentrations.
      Surprisingly, it is observed that gels are formed despite the fact that the
      binding sites of the laponite RD particles are almost covered but the polymer
      size is too small to prevent aggregation. The gelation rate is correlated to
      structure and thermodynamics of these systems. Namely, when the balance between
      the steric forces and the depletion attractive forces undergoes an abrupt change
      the gelation time also undergoes a sharp variation. For lower and comparable Mw,
      PPO speeds up the gelation more efficiently than PEO while for higher Mw the
      gelation kinetics is slowed down again. Interestingly, copolymers of PEO and PPO
      blocks do not induce gelation in the time-window where the homopolymers do.

PMID- 18620454
TI  - Cadinane sesquiterpenes from the leaves of Eupatorium adenophorum.
AB  - Four new cadinane sesquiterpenes (1- 4), including a dimeric cadinane derivative
      (2) and a peroxide cadinane analogue (3), have been isolated from the leaves of
      Eupatorium adenophorum. Their structures including absolute configurations were
      determined on the basis of spectroscopic data interpretation and single-crystal X
      ray crystallography. Compound 4 showed in vitro cytotoxicity against the HCT-8,
      Bel-7402, and A2780 cancer cell lines.

PMID- 18620456
TI  - Chemoselective N-acylation via condensations of N-(benzoyloxy)amines and alpha
      ketophosphonic acids under aqueous conditions.
AB  - A new amide-forming reaction with N-benzoyloxyamines and alpha-ketophosphonic
      acids was investigated. A mixed solvent of t-BuOH/water (1:1) at 40 degrees C
      provided the desired amide in high yield (71-96%). Both phosphonic acids ( 9, 12,
      or 13) and their disodium salts (e.g., 10) were shown to react with the
      respective N-benzoyloxyamines ( 1b and 4) in excellent yields. The phosphonic
      acid methyl ester monosodium salt 11 did not react under these conditions.
      However, compound 11 did provide the desired amide in 22% yield upon addition of
      2 equiv of TFA. The N-acylation reaction is highly chemoselective for N
      benzoyloxyamines as both aliphatic amines and N-hydroxylamines were shown not to
      react productively with the alpha-ketophosphonic acids under the conditions
      tested. Moreover, the alpha-ketophosphonic acids are more selective than the
      related alpha-ketocarboxylic acid systems, which react with both the N
      hydroxylamines and N-benzoyloxyamines. In this regard, this novel phosphonic acid
      methodology provides a new high-yielding, chemoselective acylating reagent for
      further study.

PMID- 18620457
TI  - Waiting for reimbursement of new medicines in Canada: it's time for a rethink.
AB  - Available evidence indicates that patients who have private sector drug insurance
      are immediately covered for all new medically necessary drugs certified by Health
      Canada, with few exceptions. The experience for patients who are dependent on
      public drug programmes is much worse. Evidence indicates that, on average across
      the provinces, far less than half of the drugs certified by Health Canada are
      finally approved by the provinces for public reimbursement. Publicly insured
      patients also wait up to 1 year longer than privately insured patients to get
      insurance coverage for new drugs. Evidence also shows that public drug coverage
      varies widely across provinces.

PMID- 18620458
TI  - Modelling approaches: the case of schizophrenia.
AB  - Schizophrenia is a chronic disease characterized by periods of relative stability
      interrupted by acute episodes (or relapses). The course of the disease may vary
      considerably between patients. Patient histories show considerable inter- and
      even intra-individual variability. We provide a critical assessment of the
      advantages and disadvantages of three modelling techniques that have been used in
      schizophrenia: decision trees, (cohort and micro-simulation) Markov models and
      discrete event simulation models. These modelling techniques are compared in
      terms of building time, data requirements, medico-scientific experience,
      simulation time, clinical representation, and their ability to deal with patient
      heterogeneity, the timing of events, prior events, patient interaction,
      interaction between co-variates and variability (first-order uncertainty). We
      note that, depending on the research question, the optimal modelling approach
      should be selected based on the expected differences between the comparators, the
      number of co-variates, the number of patient subgroups, the interactions between
      co-variates, and simulation time. Finally, it is argued that in case micro
      simulation is required for the cost-effectiveness analysis of schizophrenia
      treatments, a discrete event simulation model is best suited to accurately
      capture all of the relevant interdependencies in this chronic, highly
      heterogeneous disease with limited long-term follow-up data.

PMID- 18620459
TI  - Assessing the impact of global price interdependencies.
AB  - Documented launch delays and the ensuing debate over their underlying causes have
      focused on assessment from the individual country's perspective. Seen in a larger
      game theoretical framework this may cause problems, because although the
      countries see an individual game, the pharmaceutical firm sees a repeated linked
      game. The links are due to external reference pricing and parallel trade.
      Behaviours that are optimal in the single, individual game (for either the
      country or the pharmaceutical firm) may no longer be optimal when considering the
      global repeated game. A theoretical mixed integer linear model of the firm's
      launch and pricing decisions is presented along with examples wherein
      international price dependencies most likely played a role. This model can help
      countries understand the implication of their external reference pricing policies
      on the global repeated pricing game. Understanding the behaviour of the
      pharmaceutical firm in this global context aids countries in designing policies
      to maximize the welfare of their citizens.

PMID- 18620460
TI  - Conducting discrete choice experiments to inform healthcare decision making: a
      user's guide.
AB  - Discrete choice experiments (DCEs) are regularly used in health economics to
      elicit preferences for healthcare products and programmes. There is growing
      recognition that DCEs can provide more than information on preferences and, in
      particular, they have the potential to contribute more directly to outcome
      measurement for use in economic evaluation. Almost uniquely, DCEs could
      potentially contribute to outcome measurement for use in both cost-benefit and
      cost-utility analysis. Within this expanding remit, our intention is to provide a
      resource for current practitioners as well as those considering undertaking a
      DCE, using DCE results in a policy/commercial context, or reviewing a DCE. We
      present the fundamental principles and theory underlying DCEs. To aid in
      undertaking and assessing the quality of DCEs, we discuss the process of carrying
      out a choice study and have developed a checklist covering conceptualizing the
      choice process, selecting attributes and levels, experimental design,
      questionnaire design, pilot testing, sampling and sample size, data collection,
      coding of data, econometric analysis, validity, interpretation and welfare and
      policy analysis. In this fast-moving area, a number of issues remain on the
      research frontier. We therefore outline potentially fruitful areas for future
      research associated both with DCEs in general, and with health applications
      specifically, paying attention to how the results of DCEs can be used in economic
      evaluation. We also discuss emerging research trends. We conclude that if
      appropriately designed, implemented, analysed and interpreted, DCEs offer several
      advantages in the health sector, the most important of which is that they provide
      rich data sources for economic evaluation and decision making, allowing
      investigation of many types of questions, some of which otherwise would be
      intractable analytically. Thus, they offer viable alternatives and complements to
      existing methods of valuation and preference elicitation.

PMID- 18620461
TI  - Demand forecasting for preventive AIDS vaccines: economic and policy dimensions.
AB  - BACKGROUND: An AIDS vaccine could play a very significant role in reversing the
      HIV pandemic, saving millions of lives. For a vaccine to have such an impact, it
      must be widely available and adopted and taken up rapidly in the countries most
      affected. A demand-forecasting model provides a valuable tool that can guide R&D
      spending decisions and identify policy actions to help achieve these goals.
      OBJECTIVE: To identify the key determinants of vaccine demand, model global
      adoption and uptake dynamics, estimate potential demand and revenues associated
      with future preventive AIDS vaccines, and to conduct sensitivity analyses to
      assess the impact of each parameter on demand. METHODS: A discrete,
      deterministic, linear, predictive mathematical model based on stratified
      population averages with a 30-year time horizon was developed to assess scenarios
      of future demand. This forecasting model was used to explore the effects of
      vaccine characteristics and a variety of regulatory, political, financial and
      health service factors on future demand and revenues. The intervention modelled
      was a preventive AIDS vaccine (efficacy: 30-90%; duration of protection: 3-5
      years; in a two-dose prime-boost combination). The main outcome measure was the
      number of complete courses of vaccine administered. RESULTS: The model suggests
      that demand for a preventive AIDS vaccine with a medium efficacy (50%) and
      duration of protection (3 years) would average 68 million courses annually over a
      30-year period. Under different scenarios, demand would peak at 38-152 million
      courses annually. On the basis of tiered pricing across public and private
      markets ($US2-100 per dose), these levels of peak demand would translate into
      $US2.5-5.5 billion in peak annual sales revenues. Private markets and high-income
      countries account for small volumes but large shares of projected revenues, while
      low-income countries account for large volumes and more modest, but still
      significant, sales revenues. Vaccinations to 'catch-up' those who are missed or
      not eligible for routine annual programmes (whether adolescent or high-risk
      populations) would account for 20-35% of cumulative vaccination courses across
      all scenarios. Demand was found to be sensitive to vaccine efficacy, duration of
      protection and price. Efforts to expedite regulatory review processes, improve
      immunization infrastructure and reduce political constraints could increase
      demand for an AIDS vaccine by 40 million additional courses a year compared with
      the medium efficacy (baseline) vaccine forecast. CONCLUSIONS: Our model can
      provide vaccine developers with credible estimates of market potential for an
      AIDS vaccine, and with a tool that can be used to improve forecasts over time as
      AIDS vaccine science progresses. It can also help governments to identify and
      pursue those policies that could best strengthen demand and uptake of a safe and
      effective preventive AIDS vaccine.

PMID- 18620462
TI  - Trastuzumab: a pharmacoeconomic review of its use in early breast cancer.
AB  - Trastuzumab (Herceptin) is a monoclonal antibody approved for the treatment of
      breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2).
      Well designed clinical trials in women with early breast cancer have demonstrated
      that 1 years' therapy with adjuvant intravenous trastuzumab (a loading dose
      followed by 6 mg/kg every 3 weeks or 2 mg/kg weekly) significantly improves
      disease-free survival and overall survival compared with observation (subsequent
      to chemotherapy) or chemotherapy alone in women with HER2-positive disease. In
      the HERA trial, disease-free survival was estimated to improve by 6.3% at 3 years
      in the trastuzumab group compared with the observation group. Trastuzumab is
      generally well tolerated. The most common adverse events are infusion-related
      symptoms, such as fever and chills, which usually occur with administration of
      the first dose. Cardiotoxicity occurs in a small proportion of patients receiving
      trastuzumab, particularly when coadministered with anthracyclines, and cardiac
      assessment is recommended for all patients at baseline and at 3-monthly
      intervals. In modelled cost-effectiveness analyses based on data from clinical
      trials in patients with HER2-positive early breast cancer, adjuvant trastuzumab
      was predicted to be cost effective from a healthcare payer or societal
      perspective in several countries. Incremental costs per QALY or life-year gained
      with trastuzumab administered subsequent to or concurrent with chemotherapy
      compared with chemotherapy alone were consistently within accepted local
      thresholds for cost effectiveness. Sensitivity analyses demonstrated that these
      results remained generally robust to plausible changes in key model assumptions.
      In conclusion, in patients with HER2-positive early breast cancer, the addition
      of adjuvant trastuzumab is clinically effective in improving disease-free
      survival. Available pharmacoeconomic data from several countries, despite some
      inherent limitations, support the use of adjuvant trastuzumab for 1 year as a
      cost-effective treatment relative to chemotherapy alone in this patient
      population.

PMID- 18620463
TI  - A physiological and psychological basis for anti-pronation taping from a critical
      review of the literature.
AB  - Anti-pronation taping is a treatment technique commonly used by clinicians in the
      management of lower extremity musculoskeletal pain and injury. The clinical
      efficacy of anti-pronation tape is described anecdotally and has some support
      through clinical trials for some foot conditions. However, the mechanism(s)
      underlying its clinical efficacy is unknown, but are broadly categorized under
      mechanical, neurophysiological and psychological hypotheses. This article
      explores these hypotheses and contributes to the understanding of the technique.A
      computer database search was conducted to identify relevant experimental studies
      using an a priori defined search strategy. Data were extracted from reviewed
      articles and wherever possible mean differences between baseline and taped
      condition and the 95% confidence interval, as well as percentage change scores
      and effect size statistics were calculated. Articles were organized pertaining to
      the hypothetical mechanism investigated and presented accordingly into
      biomechanical, neurophysiological or psychological paradigms.Overall, the
      research to date has focused predominantly on the mechanical paradigm with far
      fewer papers being found for the neurophysiological and psychological paradigms.
      The literature provides evidence that anti-pronation tape has a biomechanical
      effect, which has been demonstrated by increases in navicular height and medial
      longitudinal arch height, reductions in tibial internal rotation and calcaneal
      eversion and alteration of plantar pressure patterns, under both static (i.e.
      standing) and dynamic (i.e. walking, jogging, running) conditions. The reduction
      in pronation was dependent on the surrogate measure of pronation used, but
      generally ranged from as little as 5% increase in longitudinal arch height during
      jogging to as much as a 33% change in calcaneal eversion during walking.
      Preliminary evidence from few studies suggests that anti-pronation tape has a
      neurophysiological effect as it has been shown to reduce the activity of several
      muscles of the leg during dynamic tasks such as walking, hopping, cutting, back
      pedalling and drop jumps. Data were difficult to extract from these papers, but
      it would appear from a small study that the reduction is in the order of about
      45% for tibialis posterior. To date, there has been limited investigation of the
      psychological effects of anti-pronation tape. A main issue, as with most placebo
      or sham interventions for physical therapy research, is that of an appropriate
      comparator in this regard. Consequently, these effects are currently not well
      understood. This article reports of evidence in support of anti-pronation tape
      exerting a biomechanical effect. As its name suggests, it does reduce pronation.
      There is emerging evidence of a neurophysiological effect, which is generally one
      of reduction in muscle activity, but caution is urged in over-interpreting a few
      studies on small sample sizes. Further research is required in this paradigm
      before sports medicine practitioners can utilize these findings in day-to-day
      clinical practice. Due to insufficient evidence, this article was unable to draw
      any conclusions as to the psychological effects of the tape, but the article does
      prompt the need for further exploration into the possible role of placebo in the
      clinical effects of anti-pronation taping.

PMID- 18620465
TI  - Influence of running velocity on vertical, leg and joint stiffness : modelling
      and recommendations for future research.
AB  - Human running can be modelled as either a spring-mass model or multiple springs
      in series. A force is required to stretch or compress the spring, and thus
      stiffness, the variable of interest in this paper, can be calculated from the
      ratio of this force to the change in spring length. Given the link between force
      and length change, muscle stiffness and mechanical stiffness have been areas of
      interest to researchers, clinicians, and strength and conditioning practitioners
      for many years. This review focuses on mechanical stiffness, and in particular,
      vertical, leg and joint stiffness, since these are the only stiffness types that
      have been directly calculated during human running. It has been established that
      as running velocity increases from slow-to-moderate values, leg stiffness remains
      constant while both vertical stiffness and joint stiffness increase. However, no
      studies have calculated vertical, leg or joint stiffness over a range of slow-to
      moderate values to maximum values in an athletic population. Therefore, the
      effects of faster running velocities on stiffness are relatively unexplored.
      Furthermore, no experimental research has examined the effects of training on
      vertical, leg or joint stiffness and the subsequent effects on running
      performance. Various methods of training (Olympic style weightlifting, heavy
      resistance training, plyometrics, eccentric strength training) have shown to be
      effective at improving running performance. However, the effects of these
      training methods on vertical, leg and joint stiffness are unknown. As a result,
      the true importance of stiffness to running performance remains unexplored, and
      the best practice for changing stiffness to optimize running performance is
      speculative at best. It is our hope that a better understanding of stiffness, and
      the influence of running speed on stiffness, will lead to greater interest and an
      increase in experimental research in this area.

PMID- 18620464
TI  - Autonomic control of heart rate during and after exercise : measurements and
      implications for monitoring training status.
AB  - Endurance training decreases resting and submaximal heart rate, while maximum
      heart rate may decrease slightly or remain unchanged after training. The effect
      of endurance training on various indices of heart rate variability remains
      inconclusive. This may be due to the use of inconsistent analysis methodologies
      and different training programmes that make it difficult to compare the results
      of various studies and thus reach a consensus on the specific training effects on
      heart rate variability. Heart rate recovery after exercise involves a coordinated
      interaction of parasympathetic re-activation and sympathetic withdrawal. It has
      been shown that a delayed heart rate recovery is a strong predictor of mortality.
      Conversely, endurance-trained athletes have an accelerated heart rate recovery
      after exercise. Since the autonomic nervous system is interlinked with many other
      physiological systems, the responsiveness of the autonomic nervous system in
      maintaining homeostasis may provide useful information about the functional
      adaptations of the body. This review investigates the potential of using heart
      rate recovery as a measure of training-induced disturbances in autonomic control,
      which may provide useful information for training prescription.

PMID- 18620466
TI  - Exercise and primary dysmenorrhoea : a comprehensive and critical review of the
      literature.
AB  - Primary dysmenorrhoea (PD) is chronic, cyclic, pelvic, spasmodic pain associated
      with menstruation in the absence of identifiable pathology and is typically known
      as menstrual cramps or period pain. PD is the most common gynaecological disorder
      in menstruating women. Despite treatments being available for PD, relatively few
      women consult a clinician about their symptoms, preferring not to use treatment,
      or to self-treat using non-pharmacological or over-the-counter interventions. The
      notion that exercise is effective in preventing and treating symptoms has
      prevailed for many years and led to the promotion of anecdotal belief that
      exercise is beneficial. Behavioural interventions such as exercise may not only
      reduce dysmenorrhoea, but also eliminate or reduce the need for medication to
      control menstrual cramps and other associated symptoms. With emphasis on data
      from experimental studies, this report seeks to review the available evidence
      regarding the role of exercise in the management of PD and menstruation-related
      symptomatology. Using key search terms, online bibliographical databases were
      searched from the beginning of each database to 1 April 2007. Despite the
      widespread belief that exercise can reduce PD, empirical support is limited.
      Evidence from observational studies was mixed. Several observational studies
      reported that physical activity/exercise was associated with reduced prevalence
      of dysmenorrhoea, although numerous other studies found no significant
      association between outcomes. Evidence from controlled trials suggests that
      exercise can reduce PD and associated symptoms, but these have been small and of
      low methodological quality. There are, however, several plausible mechanisms by
      which exercise might be effective in the management of PD. A large randomized
      controlled trial is required before women and clinicians are advised that
      exercise is likely to be effective in reducing PD and related menstrual symptoms.

PMID- 18620469
TI  - Effectiveness of assisted reproductive technology (ART).
AB  - OBJECTIVES: We reviewed the evidence regarding the outcomes of interventions used
      in ovulation induction, superovulation, and in vitro fertilization (IVF) for the
      treatment of infertility. Short-term outcomes included pregnancy, live birth,
      multiple gestation, and complications. Long-term outcomes included pregnancy and
      post-pregnancy complications for both mothers and infants. DATA SOURCES: MEDLINE
      and Cochrane Collaboration resources. REVIEW METHODS: We included studies
      published in English from January 2000 through January 2008. For short-term
      outcomes, we excluded non-randomized studies and studies where a pregnancy or
      live birth rate per subject could not be calculated. For long-term outcomes, we
      excluded studies with fewer than 100 subjects and those without a control group.
      Articles were abstracted for relevant details, and relative risks or odds ratios,
      with 95 percent confidence intervals, were calculated for outcomes of interest
      for each study. RESULTS: We identified 5294 abstracts and (for the three
      questions discussed in this draft report) reviewed 1210 full-text articles and
      included 478 articles for abstraction. Approximately 80 percent of the included
      studies were performed outside the United States. The majority of randomized
      trials were not designed to detect differences in pregnancy and live birth rates;
      reporting of delivery rates and obstetric outcomes was unusual. Most did not have
      sufficient power to detect clinically meaningful differences in live birth rates,
      and had still lower power to detect differences in less frequent outcomes such as
      multiple births and complications. Interventions for which there was sufficient
      evidence to demonstrate improved pregnancy or live birth rates included: (a)
      administration of clomiphene citrate in women with polycystic ovarian syndrome,
      (b) metformin plus clomiphene in women who fail to respond to clomiphene alone;
      (c) ultrasound-guided embryo transfer, and transfer on day 5 post-fertilization,
      in couples with a good prognosis; and (d) assisted hatching in couples with
      previous IVF failure. There was insufficient evidence regarding other
      interventions. Infertility itself is associated with most of the adverse longer
      term outcomes. Consistently, infants born after infertility treatments are at
      risk for complications associated with abnormal implantation or placentation; the
      degree to which this is due to the underlying infertility, treatment, or both is
      unclear. Infertility, but not infertility treatment, is associated with an
      increased risk of breast and ovarian cancer. CONCLUSIONS: Despite the large
      emotional and economic burden resulting from infertility, there is relatively
      little high-quality evidence to support the choice of specific interventions.
      Removing barriers to conducting appropriately designed studies should be a major
      policy goal.

PMID- 18620468
TI  - Palpitations in athletes.
AB  - In an athletic population, the incidence of palpitations varies from 0.3% to as
      high as 70%, depending on age and type of sport being studied. Palpitations, or
      an awareness of an increased or abnormal heart beat, are rare in the school-age
      athlete, but much more common in older endurance athletes. The majority are felt
      to be benign, with prognosis relating to type of specific rhythm disturbance and
      presence or absence of underlying heart disease. Atrial fibrillation can account
      for up to 9% of rhythm disturbances in elite athletes, and up to 40% in those
      with long-standing symptoms. In athletes with premature ventricular beats (PVCs),
      underlying heart disease is more likely to be present in those with a high PVC
      burden, defined as >/=2000 PVCs/24 hours. Choice of monitoring device is crucial
      in making a proper diagnosis of the specific rhythm disturbance. For symptoms
      occurring within a 24-hour period, simple Holter monitoring is adequate to make a
      diagnosis. However, if symptoms occur less frequently, clinicians must choose one
      of the other available monitoring devices. Most importantly, choice of device
      should depend on which device is most likely to detect the rhythm disturbance.
      Other cardiac testing such as echocardiography, stress testing, endomyocardial
      biopsy, genetic testing, electrophysiologic testing, or cardiac magnetic
      resonance imaging may be indicated as well. The majority of palpitations in
      athletes will be first identified by screening examination, or by a complaint
      from the athlete. The third and most current pre-participation examination
      monograph recommends asking the athlete if he/she has palpitations with exercise.
      The assumption has been made that palpitations occurring at rest in athletes are
      benign, but this theory has not been validated prospectively in a large cohort of
      the athletic population. Specific rhythms can often be treated with
      radiofrequency ablation, with return to sports provided there is no significant
      high risk underlying heart disease present. Athletes with known malignant
      ventricular rhythm disturbances, or underlying substrate for such, who have
      undergone implantation of an automatic implanted cardioverter-defibrillator are
      not recommended to return to sport because there is no data on the safety and
      efficacy of defibrillators in this clinical setting, and certain athletic
      activities may result in damage to the device.

PMID- 18620467
TI  - Exercise, energy balance and the shift worker.
AB  - Shift work is now common in society and is not restricted to heavy industry or
      emergency services, but is increasingly found amongst 'white collar' occupations
      and the growing number of service industries. Participation in shift work is
      associated with increased body mass index, prevalence of obesity and other health
      problems. We review the behavioural and biological disturbances that occur during
      shift work and discuss their impact on leisure-time physical activity and energy
      balance. Shift work generally decreases opportunities for physical activity and
      participation in sports. For those shift workers who are able to exercise,
      subjective and biological responses can be altered if the exercise is taken at
      unusual times of day and/or if the shift worker is sleep deprived. These altered
      responses may in turn impact on the longer-term adherence to an exercise
      programme. The favourable effects of exercise on body mass control and sleep
      quality in shift workers have not been confirmed. Similarly, recent reports of
      relationships between sleep duration and obesity have not been examined in a
      shift work context. There is no evidence that exercise can mediate certain
      circadian rhythm characteristics (e.g. amplitude or timing) for improved
      tolerance to shift work. Total energy intake and meal composition do not seem to
      be affected by participation in shift work. Meal frequency is generally reduced
      but snacking is increased on the night shift. Unavailability of preferred foods
      in the workplace, a lack of time, and a reduced desire to eat at night explain
      these findings. 'Normal' eating habits with the family are also disrupted. The
      metabolic responses to food are also altered by shift work-mediated disruptions
      to sleep and circadian rhythms. Whether any interactions on human metabolism
      exist between timing or content of food intake and physical activity during shift
      work is not known at present. There are very few randomized controlled studies on
      the efficacy of physical activity or dietary interventions during shift work.
      Some favourable effects of such interventions on fatigue levels at work have been
      reported, but biological and behavioural outcomes relevant to long-term health
      and energy balance have not been studied adequately. In addition, recruitment and
      retention of research participants for randomized controlled trials of physical
      activity or dietary interventions have been very difficult. We present a model of
      the various behavioural and biological factors relevant to exercise and energy
      balance during shift work as a framework for future research.

PMID- 18620470
TI  - Diabetes education for children with type 1 diabetes mellitus and their families.
AB  - OBJECTIVES: To determine the effectiveness of diabetes education on metabolic
      control, diabetes-related hospitalizations, complications, and knowledge, quality
      of life and other psychosocial outcomes for children with type 1 diabetes and
      their families. DATA SOURCES: A systematic and comprehensive literature review
      was conducted in 21 electronic databases of medical and health education
      literature to identify randomized controlled trials (RCTs) and observational
      studies evaluating the effectiveness of diabetes education. REVIEW METHODS: Study
      selection, quality assessment, and data extraction were conducted independently
      by several investigators in duplicate. A descriptive analysis is presented.
      RESULTS: From 12,756 citations, 80 studies were identified and included in the
      review (53 RCTs or CCTs, 27 observational studies). The methodological quality of
      studies was generally low. Most studies (35/52) that examined the effect of
      educational interventions on HbA1c found no evidence of increased effectiveness
      of the interventions over the education provided as part of standard care.
      Successful interventions were heterogeneous and included cognitive behavioral
      therapy, family therapy, skills training and general diabetes education. Most
      studies reported a positive effect on health service utilization (i.e., reduced
      use), although less than half were statistically significant. There was no clear
      evidence that educational interventions had an effect on short-term
      complications. The effect of educational interventions on diabetes knowledge was
      unclear with 12/30 studies reporting a significant improvement. Interventions
      which had varying effects on knowledge scores included diabetes camp, general
      diabetes education, and cognitive behavioral therapy. In the area of self
      management/regimen adherence, 10/21 studies reported improving this outcome
      significantly. Successful interventions included general diabetes education and
      cognitive behavioral therapy. Educational interventions were successful in
      improving various psychosocial outcomes. The results of two studies examining
      refinements to intensive therapy education suggest that educational interventions
      may enhance the effects of intensive diabetes management in reducing HbA1c.
      CONCLUSIONS Due to the heterogeneity of reported diabetes education
      interventions, outcome measures, and duration of followup, there is insufficient
      evidence to identify a particular intervention that is more effective than
      standard care to improve diabetes control or quality of life or to reduce short
      term complications.

PMID- 18620471
TI  - Outcomes of maternal weight gain.
AB  - OBJECTIVES: The RTI International-University of North Carolina at Chapel Hill
      Evidence-based Practice Center (RTI-UNC EPC) systematically reviewed evidence on
      outcomes of gestational weight gain and their confounders and effect modifiers,
      outcomes of weight gain within or outside the 1990 Institute of Medicine (IOM)
      guidelines, risks and benefits of weight gain recommendations, and anthropometric
      measures of weight gain. DATA SOURCES: We searched MEDLINE Cochrane Collaboration
      resources, Cumulative Index to Nursing & Allied Health Literature, and Embase.
      REVIEW METHODS: We included studies published in English from 1990 through
      October 2007. We excluded studies with low sample size (based on study design:
      case series <100 subjects and cohorts <40 subjects). RESULTS: Overall, strong
      evidence supported an association between gestational weight gains and the
      following outcomes: preterm birth, total birthweight, low birthweight (<2,500 g),
      macrosomia, large-for-gestational-age (LGA) infants, and small-for-gestational
      age (SGA) infants; moderate evidence supported an association for cesarean
      delivery and intermediate-term weight retention (3 months to 3 years postpartum).
      The studies reviewed provided strong evidence for the independent association of
      pregravid weight status and outcomes, moderate evidence for age and parity, and
      weak evidence for race. Regarding outcomes of weight gain within or outside 1990
      IOM guidelines, moderate to strong evidence suggests an association between
      weight gain below IOM recommendations and preterm birth, low birthweight, SGA
      birthweights, and failure to initiate breastfeeding, and strong evidence for the
      association between weight gain above IOM recommendations and high birthweight,
      macrosomia, and LGA birthweights. Moderate evidence supports an association
      between weight gain above IOM guidelines and cesarean delivery and postpartum
      weight retention in the short, intermediate, and long term. Included research is
      inadequate for objective assessments of the range of harms and benefits of
      providing all women, irrespective of age, race or ethnicity, or pregravid body
      mass index (BMI), with the same recommendation for weight gain in pregnancy.
      CONCLUSIONS: Gestational weight gain is associated with some infant and maternal
      outcomes. One weight gain recommendation for all women is not supported by the
      evidence identified in this review. To understand fully the impact of gestational
      weight gain on short- and long-term outcomes for women and their offspring will
      require that researchers use consistent definitions of weight gain during
      pregnancy, better address confounders in their analyses, improve study designs
      and statistical models, and conduct studies with longer followup.

PMID- 18620472
TI  - Effects, uptake, and fate of 2,4,6-trinitrotoluene aged in soil in plants and
      worms.
AB  - The present study was aimed at providing data to be used at predicting exposure
      based effects of 2,4,6-trinitrotoluene (TNT) aged in soil on endpoint organisms
      representing two trophic levels. These data can be used to define criteria or
      reference values for environmental management and conducting specific risk
      assessment. Long-term exposure tests were conducted to evaluate sublethal
      toxicity and uptake of aged soil-based explosives, with TNT as the main
      contaminant. In these tests, plants were exposed for 55 d, and biomass and
      explosives residues were determined. Worms were exposed for 28 and 42 d, and
      biomass, number, and tissue residues were determined. Biomass of Lolium perenne
      significantly decreased with soil-TNT concentration, and an effective
      concentration causing a 20% decrease in biomass (EC20) for TNT metabolites of
      3.75 mg/kg was calculated. The concentrations of TNT metabolites in shoots and
      roots were significantly related to concentrations in soil, as were
      concentrations of hexahydro-1,3,5-trinitro-1,3,5 triazine (RDX) and octahydro
      1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). The mean bioconcentration factors,
      indicating the potential of a chemical to accumulate in an organism, were 0.9 for
      TNT metabolites, 71.8 for RDX, and 12.2 for HMX in L. perenne shoots. Biomass of
      Eisenia fetida adults significantly decreased with soil-TNT concentration, and an
      EC20 for TNT of 3.70 mg/kg was calculated. The TNT, RDX, and HMX levels in E.
      fetida were below detection.

PMID- 18620473
TI  - Arsenic accumulation and toxicity in the earthworm Eisenia fetida affected by
      chloride and phosphate.
AB  - Chloride and phosphate (PO4) were added to field soils contaminated with arsenic
      and heavy metals, and Eisenia fetida were inoculated in these treated soils for
      70 d. After 28 d, earthworm survival, body weight, and cocoon production were
      measured. During the exposure period, the accumulation of As and four metals (Cu,
      Zn, Cd, and Pb) in E. fetida was analyzed. Bulk soils and soil solutions were
      characterized for the contents of As, metals, organic matter, and major cations
      and anions; cation exchange capacity; and pH. Although addition of Cl to the soil
      did not impact As toxicity, it significantly reduced As uptake. The addition of
      PO4 induced changes in As toxicity and reduced As accumulation even though the As
      concentration in the soil pore water increased because of the substitution of As
      by P at soil sorption sites. These results imply that the addition of Cl induced
      the formation of an As-Cl complex, thereby resulting in decreased As
      bioavailability; they also imply that monovalent phosphate (H2PO4(-)) competes
      with As for uptake through transporter-mediated mechanisms in cells.

PMID- 18620474
TI  - Effects of post-Hurricane Katrina New Orleans (LA, USA) sediments on early
      development of the Japanese medaka (Oryzias latipes).
AB  - When Hurricane Katrina struck the U.S. Gulf Coast, levees surrounding New
      Orleans, Louisiana, USA, were breached, leading to widespread flooding of the
      city and potential contamination from industrial spills, residential sources, and
      redistribution of pre-existing pollutants. We chemically characterized sediment
      samples from five New Orleans locations and used early development and
      mutagenesis in Japanese medaka (Oryzias latipes) as metrics of the toxic effects
      of these sediments. Sediment samples were analyzed for organohalogen pesticides,
      polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and metals. One
      month after Hurricane Katrina, four of the five sites had unsafe concentrations
      of arsenic and one or more pesticides, pesticide metabolites, or polycyclic
      aromatic hydrocarbons. Medaka embryonic mortality and time to hatching both
      increased during exposure to aqueous extracts of sediments, with the greatest
      toxicity observed for the most heavily contaminated sediment. Exposure to
      sediment extracts did not, however, result in significantly elevated rates of
      mutagenesis. When the most contaminated site was resampled 4.5 months later, the
      sediment had lower contaminant concentrations and fewer deleterious effects on
      medaka development. Using the medaka bioassay, therefore, we demonstrate toxic
      effects of post-Hurricane Katrina sediments immediately following the storm, with
      some amelioration over time of contaminant concentrations and their negative
      biological effects.

PMID- 18620475
TI  - Ectoparasitism by Eutrombicula alfreddugesi larvae (Acari: Trombiculidae) on
      Liolaemus tenuis lizard in a Chilean fragmented temperate forest.
AB  - We compared parasite load (prevalence and mean intensity) of Eutrombicula
      alfreddugesi larvae on the lizard Liolaemus tenuis sampled during January 2006
      and 2007 from the interior and edges of large forest tracts in the coastal
      Maulino Forest (35 degrees 59'S, 72 degrees 41'W) and from nearby forest
      fragments (1.5-20 ha). All lizards were parasitized by chiggers regardless of
      location (prevalence, 100%); however, mean intensity of infestation was
      significantly lower at forest fragment edges compared with either large forest
      interiors or forest edges. We attribute differences in mean intensity to
      differences in microclimate among localities; maximum air temperature was
      significantly higher and relative humidity significantly lower in fragment edges
      compared with either large forest tract interior or edges.

PMID- 18620476
TI  - Soap-scented skin patch for menstrual cramps: a case series.

PMID- 18620478
TI  - Some terminology needs for writers, researchers, practitioners, and editors as we
      move toward integrating medicines.

PMID- 18620477
TI  - Integrative medicine research at an academic medical center: patient
      characteristics and health-related quality-of-life outcomes.
AB  - OBJECTIVE: To characterize patients seeking care at a university-based
      integrative medicine practice, and to assess short-term changes in health-related
      quality of life (HRQoL) associated with integrative medical treatment. DESIGN:
      Prospective, observational study. SETTING: This study was conducted at a large
      U.S. academic medical center affiliated with the Consortium of Academic Health
      Centers for Integrative Medicine. PARTICIPANTS: Seven hundred and sixty-three
      (763) new patients with diverse medical conditions participated in the study.
      Mean age was 49 years (standard deviation = 16, range = 14-93). Two thirds of
      patients were women and three quarters were white. The most common International
      Classification of Diseases 9th Revision medical diagnoses were malaise and
      fatigue, myalgia and myositis, allergy, anxiety or depression, hypertension,
      malignant neoplasm of the breast, lumbago, and irritable bowel disease. Over half
      the sample had two or more comorbid medical conditions. OUTCOME MEASURE: The
      Medical Outcomes Study 36-item Short-Form (SF-36) health survey was used to
      measure HRQoL at initial assessment and 3-months following integrative medicine
      consultation. RESULTS: Baseline SF-36 scores fell below the 25th percentile,
      indicating substantially compromised HRQoL. Physician-prescribed treatment
      modalities included anthroposophical medicine, nutritional medicine, Western
      herbs, homeopathy, nutritional counseling, and acupuncture. Three (3) month
      follow-up assessment revealed statistically significant improvements on all eight
      SF-36 subscales among survey respondents. HRQoL effect sizes ranged from 0.17
      (Physical Functioning) to 0.41 (Social Functioning), with a mean of 0.30. HRQoL
      effects were consistent among demographic subgroups. CONCLUSIONS: Integrative
      medical treatment at a university-based center is associated with significant
      increases in HRQoL for a medically diverse population with substantial
      comorbidity and functional limitations. Controlled studies that measure HRQoL and
      additional outcomes related to whole person health--physical, mental, social, and
      spiritual--are needed to determine the full therapeutic potential of integrative
      medicine, and to determine efficacy and cost-effectiveness relative to
      conventional medical care.

PMID- 18620479
TI  - In vivo maturation of scaffold-free engineered articular cartilage on
      hydroxyapatite.
AB  - Tissue engineering is a promising approach, not only for cartilage, but also for
      osteochondral repair. Recent studies have demonstrated that scaffold-free
      cartilaginous tissue can be engineered using the alginate-recovered-chondrocyte
      (ARC) method. This method has also been applied to form osteochondral tissue
      using bovine articular chondrocytes and coralline hydroxyapatite (HA). The
      purpose of this study was to test whether osteochondral tissue, fabricated in
      vitro using the ARC method combined with a block of HA, would undergo maturation
      in vivo using a subcutaneous model in immunodeficient mice. Articular
      chondrocytes were isolated from the cartilage of New Zealand white rabbits and
      cultured in alginate beads. The cells with their associated matrix were recovered
      by dissolving the alginate beads with a sodium citrate buffer, resuspended in
      media and seeded onto a porous HA block. After 4 weeks of culture, some samples
      were analyzed, and others were implanted into subcutaneous pockets in nude mice.
      The analysis involved removing the cartilage portion of the de novo-formed ARC-HA
      graft and performing biochemical and histological examinations. Some samples were
      subjected to nondecalcified histology. Histological and immunohistochemical
      analyses of cartilaginous tissue were performed at 0, 2, 4, and 8 weeks after
      implantation. Biochemical characteristics were examined at 0, 4, and 8 weeks. The
      size and shape of the implanted ARC osteochondral tissue changed with time. The
      histological and immunohistochemical examination of the tissue revealed that it
      contained a cartilage-like matrix that stained strongly with Toluidine blue and
      for collagen type II. The proteoglycan (PG) content had increased significantly
      at 4 weeks from baseline. However, by 8 weeks, the PG content had decreased from
      4 weeks. The results presented here represent a possible approach to form a
      tissue-engineered osteochondral implant. Further studies are needed to improve
      biomechanical properties of the osteochondral implant to be suitable for surgical
      transplantation.

PMID- 18620480
TI  - Nanobiomechanics of repair bone regenerated by genetically modified mesenchymal
      stem cells.
AB  - Genetically modified mesenchymal stem cells (MSCs), overexpressing a BMP gene,
      have been previously shown to be potent inducers of bone regeneration. However,
      little was known of the chemical and intrinsic nanomechanical properties of this
      engineered bone. A previous study utilizing microcomputed tomography, back
      scattered electron microscopy, energy-dispersive X-ray, nanoindentation, and
      atomic force microscopy showed that engineered ectopic bone, although similar in
      chemical composition and topography, demonstrated an elastic modulus range (14.6
      22.1 GPa) that was less than that of the native bone (16.6-38.5 GPa). We
      hypothesized that these results were obtained due to the specific conditions that
      exist in an intramuscular ectopic implantation site. Here, we implanted MSCs
      overexpressing BMP-2 gene in an orthotopic site, a nonunion radial bone defect,
      in mice. The regenerated bone tissue was analyzed using the same methods
      previously utilized. The samples revealed high similarity between the engineered
      and native radii in chemical structure and elemental composition. In contrast to
      the previous study, nanoindentation data showed that, in general, the native bone
      exhibited a statistically similar elastic modulus values compared to that of the
      engineered bone, while the hardness was found to be marginally statistically
      different at 1000 muN and statistically similar at 7000 muN. We hypothesize that
      external loading, osteogenic cytokines and osteoprogenitors that exist in a
      fracture site could enhance the maturation of engineered bone derived from BMP
      modified MSCs. Further studies should determine whether longer duration periods
      postimplantation would lead to increased bone adaptation.

PMID- 18620481
TI  - Human aortic smooth muscle cells promote arteriole formation by coengrafted
      endothelial cells.
AB  - Collagen-fibronectin gels containing Bcl-2-transduced human umbilical vein
      endothelial cells (Bcl-2-HUVEC) implanted in the abdominal walls of
      immunodeficient mice form mature microvessels invested by host-derived smooth
      muscle cells (SMC) by 8 weeks. We tested the hypothesis that coengraftment of
      human aortic SMC (HASMC) could accelerate vessel maturation. To prevent SMC
      mediated gel contraction, we polymerized the gel within a nonwoven poly(glycolic
      acid) (PGA) scaffold. Implanted grafts were evaluated at 15, 30, and 60 days.
      Acellular PGA-supported protein gels elicited a macrophage-rich foreign body
      reaction and transient host angiogenic response. When transplanted alone, HASMC
      tightly associated with the fibers of the scaffold and incorporated into the
      walls of angiogenic mouse microvessels, preventing their regression. When
      transplanted alone in PGA-supported gels, Bcl-2-HUVEC retained the ability to
      form microvessels invested by mouse SMC. Interestingly, grafts containing both
      Bcl-2-HUVEC and HASMC displayed greater numbers of smooth muscle alpha-actin
      expressing cells associated with human EC-lined arteriole-like microvessels at
      all times examined and showed a significant increase in the number of larger
      caliber microvessels at 60 days. We conclude that SMC coengraftment can
      accelerate vessel development by EC and promote arteriolization. This strategy of
      EC-SMC coengraftment in PGA-supported protein gels may have broader application
      for perfusing bioengineered tissues.

PMID- 18620482
TI  - Development of defined media for the serum-free expansion of primary
      keratinocytes and human embryonic stem cells.
AB  - Primary keratinocyte (Kc) cells and human embryonic stem (hES) cells are
      routinely propagated on a mouse fibroblast feeder layer in media containing fetal
      bovine serum or other nondefined factors. One disadvantage of using these
      nondefined factors is that they may inadvertently contaminate the culture system
      with infectious agents; thus, there remains a need to develop safe culture
      conditions free from poorly defined and/or animal products. Our laboratory has
      discovered that growth factors (GFs) and vitronectin (VN) can bind to each other
      resulting in synergistic short-term functional effects in several cell types. The
      aim of the current study was to determine whether primary Kc and hES cells can be
      established and serially propagated serum-free using medium containing VN,
      insulin-like growth factor-I, and insulin-like growth factor binding protein-3
      (VN:GF). Here we demonstrate that primary Kc cells can be isolated, established,
      serially propagated, and re-form an epidermal layer using the VN:GF combination.
      Additionally, cell proliferation studies indicate that the Kcs proliferate using
      the VN:GF combination at a rate comparable to cells grown using serum. Similarly,
      we verified that this VN:GF combination could be employed for the serial
      propagation of hES cells. Importantly, both the Kc and hES cells retain their
      undifferentiated phenotype when cultured using the VN:GF combinations as a serum
      free medium for up to 4 passages for Kc and at least 10 passages for hES cells as
      indicated by the expression of a range of cell surface markers. This study
      demonstrates that the novel, fully defined VN:GF medium is a viable alternative
      to media containing serum and highlights the potential of this technology for
      generating therapeutically viable cells and tissues.

PMID- 18620483
TI  - Noninvasive assessment of glycosaminoglycan production in injectable tissue
      engineered cartilage constructs using magnetic resonance imaging.
AB  - The glycosaminoglycan (GAG) content of engineered cartilage is a determinant of
      biochemical and mechanical quality. The ability to measure the degree to which
      GAG content is maintained or increases in an implant is therefore of importance
      in cartilage repair procedures. The gadolinium exclusion magnetic resonance
      imaging (MRI) method for estimating matrix fixed charge density (FCD) is ideally
      suited to this. One promising approach to cartilage repair is use of seeded
      injectable hydrogels. Accordingly, we assess the reliability of measuring GAG
      content in such a system ex vivo using MRI. Samples of the photopolymerizable
      hydrogel, poly(ethylene oxide) diacrylate, were seeded with bovine chondrocytes
      (approximately 2.4 million cells/sample). The FCD of the constructs was
      determined using MRI after 9, 16, 29, 36, 43, and 50 days of incubation. Values
      were correlated with the results of biochemical determination of GAG from the
      same samples. FCD and GAG were found to be statistically significantly correlated
      (R2 = 0.91, p < 0.01). We conclude that MRI-derived FCD measurements of FCD in
      injectable hydrogels reflect tissue GAG content and that this methodology
      therefore has potential for in vivo monitoring of such constructs.

PMID- 18620484
TI  - Rapid large-scale expansion of functional mesenchymal stem cells from
      unmanipulated bone marrow without animal serum.
AB  - Adult mesenchymal stem cells (MSCs) are considered as valuable mediators for
      tissue regeneration and cellular therapy. This study was performed to develop
      conditions for regularly propagating a clinical quantity of > 2 x 10(8) MSCs
      without animal serum from small bone marrow (BM) aspiration volumes within short
      time. We established optimized culture conditions with pooled human platelet
      lysate (pHPL) replacing fetal bovine serum (FBS) for MSC propagation. MSC
      quality, identity, purity, and function were assessed accordingly. Biologic
      safety was determined by bacterial/fungal/mycoplasma/endotoxin testing and
      genomic stability by array comparative genomic hybridization (CGH). We
      demonstrate that unmanipulated BM can be used to efficiently initiate MSC
      cultures without the need for cell separation. Just diluting 1.5-5 mL heparinized
      BM per 500 mL minimum essential medium supplemented with L-glutamine, heparin,
      and 10% pHPL sufficiently supported the safe propagation of 7.8 +/- 1.5 x 10(8)
      MSCs within a single 11- to 16-day primary culture under defined conditions. This
      procedure also resulted in sustained MSC colony recovery. MSC purity, immune
      phenotype, and in vitro differentiation potential fully matched current criteria.
      Despite high proliferation rate, MSCs showed genomic stability in array CGH. This
      easy single-phase culture procedure can build the basis for standardized
      manufacturing of MSC-based therapeutics under animal serum-free conditions for
      dose-escalated cellular therapy and tissue engineering.

PMID- 18620485
TI  - A training model for laparoscopic urethrovesical anastomosis.
AB  - PURPOSE: To create and evaluate the effectiveness of an in vitro training model
      for laparoscopic urethrovesical anastomosis. MATERIALS AND METHODS: Chicken
      posterior trunks and porcine colons were used to construct the training model,
      which was later compared with the chicken skin model. The posterior trunk of a
      chicken was used to simulate a human pelvis, and a 3-mm cloacal stump was used to
      simulate a human urethral stump. A 15-cm segment of porcine colon with a 1-cm
      orifice was used to simulate a human bladder or neobladder. An imitation
      urethrovesical anastomosis was performed with laparoscopic instruments in a
      laparoscopic training box. The simulated urethral stump and bladder neck were
      anastomosed with six interrupted stitches. Forty urologic residents were
      randomized into two groups. The residents in group A (n = 20) practiced using
      this model for 8 hours, while those in group B (n = 20) practiced using the
      chicken skin model for 8 hours. The residents' skills were assessed using the
      porcine model before and after training. RESULTS: All residents accomplished the
      training course and both assessments. There was no significant difference between
      the groups in anastomosis time (122.65 +/- 19.98 minutes v 120.70 +/- 17.30
      minutes, P > 0.05) and quality (3.80 +/- 1.24 v 3.75 +/- 1.16, P > 0.05) before
      training. After the training sessions, both groups improved in anastomosis time
      and quality. Compared with residents in group B, residents in group A required
      less time (63.55 +/- 11.08 minutes v 76.55 +/- 12.46 minutes, P < 0.05) and
      achieved a higher quality score (8.80 +/- 1.00 v 7.65 +/- 0.88, P < 0.05).
      CONCLUSION: This training model more accurately resembles the structure and
      characteristic of the human pelvis, urethral stump, and bladder (neobladder). In
      addition, all the materials needed for this model are inexpensive and easily
      obtained. Therefore, it is an effective, convenient training model for
      laparoscopic urethrovesical anastomosis.

PMID- 18620486
TI  - A neural network model for cell classification based on single-cell biomechanical
      properties.
AB  - The potential success of tissue engineering or other cell-based therapies is
      dependent on factors such as the purity and homogeneity of the source cell
      populations. The ability to enrich cell harvests for specific phenotypes can have
      significant effects on the overall success of such therapies. While most
      techniques for cell sorting or enrichment have relied on cell surface markers,
      recent studies have shown that single-cell mechanical properties can serve as
      identifying markers of phenotype. In this study, a neural network modeling
      approach was developed to classify mesenchymal-derived primary and stem cells
      based on their biomechanical properties. Cell sorting was simulated using
      previously published data characterizing the mechanical properties of several
      different cell types as measured by atomic force microscopy. Neural networks were
      trained using combined data sets, with the resultant groupings analyzed for their
      purity, efficiency, and enrichment. Heterogeneous populations of zonal
      chondrocytes, chondrosarcoma cells, and mesenchymal-lineage cells, respectively,
      could all be classified into enriched subpopulations. Additionally, adult stem
      cells (adipose-derived or bone marrow-derived) separated disproportionately into
      nodes associated with the three primary mesenchymal lineages examined. These
      findings suggest that mathematical approaches such as neural network modeling, in
      combination with novel measures of cell properties, may provide a means of
      classifying and eventually sorting mixed populations of cells that are otherwise
      difficult to identify using more established techniques. In this respect, the
      identification of biomechanically based cell properties that increase the
      percentage of stem cells capable of differentiating into predictable lineages may
      improve the overall success of cell-based therapies.

PMID- 18620488
TI  - Differential interaction of retroviral vector with target cell: quantitative
      effect of cellular receptor, soluble proteoglycan, and cell type on gene delivery
      efficiency.
AB  - Retroviral vectors are powerful tools for gene therapy and stem cell engineering.
      To improve efficiency of retroviral gene delivery, quantitative understanding of
      interactions of a retroviral vector and a cell is crucial. Effects of nonspecific
      adsorption of retrovirus on a cell via proteoglycans and receptor-mediated
      binding of retrovirus to a cell on overall transduction efficiency were
      quantified by combining a mathematical model and experimental data. Results
      represented by transduction rate constant, a lumped parameter of overall
      transduction efficiency, delineated that chondroitin sulfate C (CSC) plays dual
      roles as either enhancer or inhibitor of retroviral transduction, depending on
      its concentrations in the retroviral supernatant. At the concentration of 20
      microg/mL, CSC enhanced the transduction efficiency up to threefold but inhibited
      more than sevenfold at the concentration of 100 microg/mL. Transduction rate
      constants for amphotropic retroviral infection of NIH 3T3 cells under phosphate
      depleted culture condition showed a proportional relationship between cellular
      receptor density on a cell and transduction efficiency. It was finally shown that
      amphotropic retrovirus transduced human fibroblast HT1080 cells more efficiently
      than NIH 3T3 cells. On the contrary, the transduction efficiency of NIH 3T3 cells
      by vesicular stomatitis virus G protein pseudotyped retroviruses was eightfold
      higher than that of HT1080 cells. This study implies usefulness of using
      quantitative analysis of retroviral transduction in understanding and optimizing
      retroviral gene delivery systems for therapeutic approaches to tissue
      engineering.

PMID- 18620487
TI  - Effects of initial seeding density and fluid perfusion rate on formation of
      tissue-engineered bone.
AB  - We describe a novel bioreactor system for tissue engineering of bone that enables
      cultivation of up to six tissue constructs simultaneously, with direct perfusion
      and imaging capability. The bioreactor was used to investigate the relative
      effects of initial seeding density and medium perfusion rate on the growth and
      osteogenic differentiation patterns of bone marrow-derived human mesenchymal stem
      cells (hMSCs) cultured on three-dimensional scaffolds. Fully decellularized
      bovine trabecular bone was used as a scaffold because it provided suitable
      "biomimetic" topography, biochemical composition, and mechanical properties for
      osteogenic differentiation of hMSCs. Trabecular bone plugs were completely
      denuded of cellular material using a serial treatment with hypotonic buffers and
      detergents, seeded with hMSCs, and cultured for 5 weeks. Increasing seeding
      density from 30 x 10(6) cells/mL to 60 x 10(6) cells/mL did not measurably
      influence the characteristics of tissue-engineered bone, in contrast to an
      increase in the perfusion rate from 100 microms(-1) to 400 microms(-1), which
      radically improved final cell numbers, cell distributions throughout the
      constructs, and the amounts of bone proteins and minerals. Taken together, these
      findings suggest that the rate of medium perfusion during cultivation has a
      significant effect on the characteristics of engineered bone.

PMID- 18620489
TI  - Interferon-gamma receptors in HIV-1 infection.
AB  - We studied in vitro production of interferon-gamma and expression of interferon
      gamma receptors (R1 and R2) by the peripheral blood mononuclear cells of 24 HIV-1
      infected patients and 12 healthy volunteers. Interferon-gamma production was
      lower in HIV-1-infected patients compared with healthy volunteers (p < 0.05), and
      it further declined in patients with lower CD4+ T-cell counts. In contrast,
      expression of interferon-gamma R1 by CD4+ T lymphocytes was higher in HIV
      infected patients than healthy volunteers (25% versus 10%, p < 0.05). In the HIV
      infected group, interferon-gamma R1 expression increased with a decline in CD4+ T
      cell count (r = -0.64, p < 0.001). Interferon-gamma R2 expression directly
      correlated with interferon-gamma R1 expression (p < 0.001). When stimulated with
      heat-killed Mycobacterium avium complex (MAC) and phorbol myristic acetate (PMA),
      the mononuclear cells of patients with advanced HIV-1 infection had lowered
      ability to produce additional interferon-gamma (either MAC or PMA) and interferon
      gamma receptors (MAC). In conclusion, with progression of HIV-1 infection,
      interferon-gamma production declines whereas expression of interferon-gamma
      receptors (R1 and R2) increases. Persistent upregulation of both interferon-gamma
      R1 and R2 receptors probably favors development of type 2 T-helper cells
      environment and promotes viral replication. This dysfunction in the interferon
      gamma pathway contributes to a further impairment in cellular immune function in
      patients with advanced HIV-1 infection, which may further increase susceptibility
      to opportunistic infections.

PMID- 18620490
TI  - Short communication: high prevalence of drug-resistant human immunodeficiency
      virus type 1 in treatment-naive patients in Greenland.
AB  - A molecular epidemiologic study of HIV-1 in Greenland showed distinct
      transmission clusters correlated with demographic and behavioral data. Resistance
      mutations were found in a majority of the pol sequences. The objective of the
      present study was to estimate prevalence of drug resistance in Greenland and
      identify transmission chains by comparing resistance data with phylogeny and
      treatment history. Of 60 untreated patients, 15 (25%) had primary resistance
      mutations. The most prevalent mutations were T69D/N (15%), K70R (15%), and M184V
      (10%). Four possible transmission chains were identified based on phylogeny and
      mutation profiles. The clusters consisted of treated and untreated patients and
      showed the same mutation profiles in both resistance and nonresistance positions.
      Prevalence of transmitted drug resistance in Greenland (25%) is higher than in
      Denmark where only 3% transmission was observed. Suboptimal use of nucleoside
      reverse transcriptase inhibitor (NRTI) in Greenland was reflected in the high
      prevalence of NRTI-related resistance in the patients. A combination of phylogeny
      and genotypic resistance tests enabled us to study the number of transmissions
      and how the virus was transmitted. Resistance mutations detected in untreated
      patients were backed up by the treatment history of index patients in the
      possible transmission chains and indicated that these drug-resistant variants
      were in fact transmitted and had not emerged due to unregistered drug intake.

PMID- 18620491
TI  - Analysis of near full-length genomic sequences of drug-resistant HIV-1 spreading
      among therapy-naive individuals in Nagoya, Japan: amino acid mutations associated
      with viral replication activity.
AB  - We analyzed a total of 12 near full-length genomes of drug-resistant HIV-1
      spreading among therapy-naive individuals in Nagoya, Japan. Genomes comprised
      seven protease inhibitor (PI)-resistant viruses possessing an M46I (n = 6) or
      L90M mutation (n = 1) and five non-nucleoside reverse transcriptase inhibitor
      resistant viruses possessing a K103N mutation. All 12 viruses conserved both an
      H87Q mutation in the cyclophilin A-binding site of Gag p24 (capsid) and a T23N
      mutation in the cysteine-rich domain of Tat protein. PI-resistant viruses
      commonly possessed two cleavage site mutations in the p6(Pol)/protease of Pol
      polyprotein (F48L in p6(Pol)) and the anchor/core domains of Nef protein (L57V).
      These amino acid mutations represent candidates for enhancing replication
      activity of drug-resistant viruses and supporting expansion of such viruses in
      therapy-naive individuals.

PMID- 18620492
TI  - Peripheral arterial disease in HIV patients older than 50 years of age.
AB  - Our objective was to analyze the prevalence of peripheral arterial disease (PAD)
      in HIV patients at risk and to compare them with the general population. All HIV
      patients older than 50 years who attended our unit from October 2005-July 2006
      and all persons attending for an annual medical checkup at an employees'
      insurance association during the same period were invited to participate in the
      study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was
      included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI)
      in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV
      patients and 99 persons from the general population of the same age and sex were
      included in the study. The HIV patients had a greater prevalence of dyslipidemia,
      diabetes, and PAD, which was symptomatic in five of them and in one subject from
      the general population. Patients with HIV infection older than 50 had a high
      prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be
      performed in this population to actively look for PAD. Control of cardiovascular
      risk factors and the use of such drugs as platelet antiaggregation agents should
      therefore be optimized in this population.

PMID- 18620493
TI  - Anti-platelet-activating factor effects of highly active antiretroviral therapy
      (HAART): a new insight in the drug therapy of HIV infection?
AB  - Platelet-activating factor (PAF) is a potent inflammatory mediator, which seems
      to play a role in the pathogenesis of several AIDS manifestations such as AIDS
      dementia complex, Kaposi's sarcoma, and HIV-related nephropathy. PAF antagonists
      have been studied in these conditions with promising results. In order to examine
      the possible interactions between PAF and antiretroviral therapy, we studied the
      effect of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse
      transcriptase inhibitors, and protease inhibitors against PAF biological
      activities and its basic biosynthetic enzymes dithiothreitol-insensitive PAF
      cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT),
      as well as its main degradative enzyme PAF-acetylhydrolase, of human mesangial
      cell line (HMC). We also studied the effect of several backbones and highly
      active antiretroviral therapy (HAART) regimens against PAF activity. Among the
      drugs tested, several inhibited PAF-induced platelet aggregation in a
      concentration-depended manner, with tenofovir, efavirenz, and ritonavir
      exhibiting the higher inhibitory effect. In addition, when these drugs were
      combined in backbones and HAART regimens based on American antiretroviral therapy
      proposals, they also synergistically exhibited an inhibitory effect against PAF
      induced platelet aggregation. Several of these drugs have also inhibited in vitro
      microsomal PAF-CPT activity, and concentrations of lopinavir-r or tenofovir-DF
      (similar to their IC(50) against PAF-induced platelet aggregation) exhibited the
      same effect against PAF-CPT and Lyso-PAF-AT when added in the cell medium of
      cultured HMC. In addition, in naive patients treated with one of the most potent
      anti-PAF HAART regimens (efavirenz/emtricitabine/tenofovir-DF) for a period of 1
      month, a significant reduction of the specific activity of PAF-CPT of washed
      human leukocytes of these patients was also observed, compared with its levels
      before the HAART treatment. These promising results need to be further studied
      and confirmed by additional in vivo tests in order to optimize HAART efficacy.

PMID- 18620494
TI  - Proliferation and foxp3 expression in virus-specific memory CD8+ T lymphocytes.
AB  - Foxp3 plays a critical role in development of CD4+ regulatory T lymphocytes
      (Tregs). It was originally proposed as a specific marker for Tregs, but recent
      studies have shown that Foxp3 can be expressed in proliferating CD8+ and CD4+ T
      lymphocytes. We further investigated the association between Foxp3 expression and
      proliferation of peripheral blood CD4+ and CD8+ T lymphocytes and focused on
      virus-specific memory CD8+ T lymphocytes. We found that resting peripheral blood
      bulk and cytomegalovirus- or HIV-1-specific CD8+ T lymphocytes do not normally
      express Foxp3. However, stimulation in vitro triggered these cells to express
      Foxp3 as well as CD25, and the addition of interleukin-2 possibly enhanced the
      expression of Foxp3. These data demonstrate that proliferation itself is
      sufficient to induce the Treg-like phenotype. Given that others have demonstrated
      Treg functional activity in such "induced Tregs," these results suggest that
      virus-specific CD8+ T lymphocytes have the capacity to acquire regulatory
      functions. Although the implications of Foxp3 expression in virus-specific CD8+ T
      lymphocytes in the immunologic control of persistent HIV-1 viremia remain to be
      determined, our results are consistent with Foxp3 expression playing an essential
      role in regulation of cell proliferation and functional outcomes for HIV-1
      specific CD8+ T lymphocytes.

PMID- 18620496
TI  - Quantification of simian immunodeficiency virus cytotoxic T lymphocyte escape
      mutant viruses.
AB  - Escape from cytotoxic T-lymphocyte (CTL) pressure is common in HIV-1 infection of
      humans and simian immunodeficiency virus (SIV) infections of macaques. CTL escape
      typically incurs a fitness cost as reversion back to wild-type can occur upon
      transmission. We utilized sequence-specific primers and DNA probes with real-time
      polymerase chain reaction (PCR) to sensitively and specifically track wild-type
      and escape mutant viremia at the Mane-A*17-restricted SIV Gag(371379) epitope AF9
      in pigtail macaques. The generation of minor escape mutant populations is
      detected by the real-time PCR 2 weeks earlier than observed using standard
      sequencing techniques. We passaged the AF9 CTL escape mutant virus into two naive
      Mane-A*17-negative pigtail macaques and showed that reversion to wild-type was
      rapid during acute infection and then slowed considerably at later stages of the
      infection. These data help refine our understanding of how CTL escape mutant
      viruses evolve.

PMID- 18620495
TI  - A therapeutic SIV DNA vaccine elicits T-cell immune responses, but no sustained
      control of viremia in SIVmac239-infected rhesus macaques.
AB  - The immunologic and virologic outcome of therapeutic DNA-vaccines administered
      during antiretroviral therapy (ART) using electroporation with or without
      (interleukin) IL-2 treatment was evaluated in the SIVmac239/macaque model. Rhesus
      macaques inoculated with pathogenic SIVmac239 were treated with ART [(R(-9-(2
      phosphonomethoxypropyl) adenine) (PMPA), FTC, Zerit] from weeks 13 to 41
      postinfection (wpi). Group 1 (n = 7) received ART only, groups 2 and 3 (each n =
      6) additionally received SIVmac239-derived gp140Env, GagPol, and TatRevNef
      plasmids by in vivo electroporation at 22, 26, 30, and 34 wpi, and group 3 also
      IL-2 for 14 days after each vaccination. Endpoints evaluated were viral load,
      Gag(181189)-specific CD8+ T-cell responses in MamuA01+ animals,
      lymphoproliferative responses, and CD4 T-cell counts. Viremia in all animals
      dropped below 200 RNA copies/ml during ART. Frequencies of Gag(181189)-specific
      CD8+ T cells prior to ART were detectable in all three groups (1.27-3.01%) and
      increased significantly (p < 0.01) postvaccination with maximum responses after
      the fourth immunization (0.2% versus 3.49-7.15%). Gag(181189)-specific CD8+ T
      cell frequencies increased post-ART cessation in all groups and remained at
      significantly higher levels (p < 0.001) until the end of the study (75 wpi) in
      both groups of vaccinated animals. Lymphoproliferative responses were detected
      against Gag in a limited number of animals after vaccination and post-ART.
      However, plasma RNA viral loads rebounded after ART termination to similar levels
      in all three groups, but remained below 10(5) copies/ml until the end of the
      study, which could be a late effect of the triple drug therapy.

PMID- 18620497
TI  - Laparoscopic orchiopexy for treating inguinal canalicular palpable undescended
      testis.
AB  - BACKGROUND AND PURPOSE: This study investigated the safety and efficacy of using
      the minimally invasive operation of laparoscopic orchiopexy to treat palpable
      inguinal canalicular undescended testes. PATIENTS AND METHODS: Laparoscopic
      orchiopexy was performed on 90 Chinese patients (103 testes) with inguinal
      canalicular palpable undescended testes. Patients with testes that were
      nonpalpable, ectopic, retractable, or palpable but distal to the external ring
      were excluded. Patients in the study ranged from 8 months to 6 years old (mean
      age: 17 months). Of the 103 testes undergoing operation, 26.7% were on the left
      side of the body and 58.9% were on the right; 14.4% of the patients had bilateral
      undescended testes. Laparoscopic techniques were used by the same surgeon to move
      the spermatic vessels and transfer the testis into the scrotum. RESULTS: All 103
      testes were successfully descended by laparoscopy. In the first 46 unilateral
      cases, the operation took significantly longer for the first 15 patients than the
      next 31, which were completed in 32.7 +/- 5.2 min. Of all 90 patients, a
      complication was encountered in only one, and this occurred at the beginning of
      the surgeon's learning curve. Of 77 unilateral undescended testes, a patent
      processes vaginalis was found in 90.3% of the cases on the ipsilateral side and
      15.6% on the contralateral side. All of the testes maintained an adequate size
      and intrascrotal position with no atrophy or recurrent inguinal hernia during a
      follow-up of 6 to 12 months. CONCLUSIONS: The laparoscopic approach to orchiopexy
      is a safe way to descend the inguinal canalicular palpable testis. It offers
      several advantages of a minimally invasive technique and yield effective results.

PMID- 18620498
TI  - Ayurvedic medicine and renal calculi.
AB  - OBJECTIVE: To explore the supportive evidence for the use of Ayurvedic medicine
      in the management of existing and recurrent nephrolithiasis. METHOD: Nine
      Ayurvedic medicines commonly utilized in the management of nephrolithiasis were
      identified by discussions with Ayurvedic practitioners in India. Mechanistic and
      clinical studies evaluating the use of these agents were identified using the
      Medline database and bibliographies suggested by Ayurvedic practitioners. The
      articles were then critically reviewed and summarized. RESULTS: Four in vitro
      mechanistic studies, eight animal studies, and seven human trials were
      identified. Phyllanthus niruri has undergone mechanistic in vitro, animal, and
      clinical trials that support its impact on calcium oxalate crystallization.
      Preliminary clinical trials have evaluated the role of Dolichos biflorus and
      Orthosiphon grandiflorus in the prevention of urolithiasis and fish stone as a
      method of stone expulsion, yet the treatment effect and mechanism of action
      remains to be elucidated. CONCLUSION: Ayurvedic medicine holds promise as a
      complementary approach to the management and prevention of nephrolithiasis. The
      best studied compound is P. niruri. Further controlled randomized clinical trials
      are justified to support or refute the potential benefits demonstrated in these
      initial studies.

PMID- 18620499
TI  - A fast method to identify renal vessels during retroperitoneal laparoscopic
      nephrectomy.
AB  - PURPOSE: To evaluate a fast method to identify renal vessels during
      retroperitoneal laparoscopic nephrectomy. METHODS: One hundred fifty
      retroperitoneal laparoscopic nephrectomies were performed from October 2003 to
      June 2006. The renal arteries were identified by following five steps: location,
      pulling, apophysis, pulsation,and fibrin. Then the renal arteries were severed or
      ligatured with a linear cutter or Hem-o-lok clips. The renal veins were exposed
      by dissecting toward the abdominal side under the renal arteries. The management
      for the renal veins was the same with that of the renal arteries. The fast method
      to identify the renal vessels during retroperitoneal laparoscopic nephrectomy
      were evaluated. RESULTS: All 150 procedures were successfully completed, and the
      renal vessels could be identified in short time. The average time to operation
      was 90 min (range 45-120 min) with average blood loss of 105 mL (range 10-510
      mL). The average specimen weight was 494 g (range 140-890 g). Intake of usual
      diet and walking were allowed within 3 days for all patients. Drains were removed
      within 2-4 postoperative days. No patient was converted into an open surgery and
      blood transfusion. Minor complications were found in 12 cases (8%), and no severe
      complication occurred in any of the 150 cases. The median time to hospitalization
      was 6.3 days. Following the five steps, the renal vessels could be identified
      quickly and easily. The duration of the operations, the risk of conversion to the
      open surgery, and the vessel injury were decreased. CONCLUSIONS: Renal vessels
      could be identified quickly by the following the five steps during
      retroperitoneal laparoscopic nephrectomy: location, pulling, apophysis,
      pulsation, and fibrin. It proved to be a useful method suitable for clinic
      application.

PMID- 18620500
TI  - Phenytoin metabolite renal calculus: an index case.
AB  - INTRODUCTION: Drugs and their metabolites are known factors in 1% to 2% of all
      kidney stones. Certain antiepileptic drugs are known to cause stone formation.
      Phenytoin is used as a first line antiepileptic therapy for many seizure
      disorders. We present what we believe to be the first report of a phenytoin
      metabolite urinary stone. METHODS: A 79-year-old woman with a fever and seizure
      disorder was found to have a right pelvic kidney with hydronephrosis and multiple
      large calcifications. She had been taking the antiepileptic medication phenytoin
      for the past 10 years. Average total serum phenytoin level from the year prior
      was in the normal range. Free phenytoin levels were not routinely monitored, but
      the one value available was elevated at 5.1 ng/dL. The patient underwent a
      percutaneous nephrolitomy, ultimately expiring from medical complications after
      the procedure. Final stone analysis revealed a composition of 35% phenytoin
      metabolite (5-(para-hydroxyphenyl)-5-phenylhydantoin) and 65% proteinaceous
      material. An extensive review of literature including PubMed, MedLine, and
      various internet search engines was performed, searching for any prior reports of
      urinary calculi formed from phenytoin or its metabolite. RESULTS: No previous
      reports of phenytoin or phenytoin metabolite urinary stones were found in the
      medical literature. Phenytoin has many known ill effects on the genitourinary
      system including acute interstitial nephritis, nephrotic syndrome, acute renal
      failure, and priapism. Now we can add urinary lithiasis to the list of its
      potential adverse effects. This article represents the first report of a
      phenytoin metabolite urinary stone. CONCLUSION: A metabolite of the commonly used
      antiepileptic medication phenytoin can cause clinically relevant urolithiasis
      leading to significant morbidity and even mortality. Clinicians should have an
      increased level of suspicion for metabolite stone formation in symptomatic
      patients taking antiepileptic medications. Further studies on phenytoin
      metabolism and its potential for inducing urinary lithiasis should be performed.

PMID- 18620502
TI  - Landmarks for consistent nerve sparing during robotic-assisted laparoscopic
      radical prostatectomy.

PMID- 18620501
TI  - Robot-assisted laparoscopic anterior pelvic exenteration for bladder cancer in
      the female patient.
AB  - INTRODUCTION: Recent small case series have now been reported for robotic
      assisted laparoscopic radical cystectomy. Herein, we describe our approach and
      initial experience with robotic-assisted laparoscopic anterior pelvic
      exenteration in the female patient with bladder cancer. METHODS: We describe the
      technique of robotic-assisted laparoscopic anterior pelvic exenteration. The
      classic da Vinci or the da Vinci S robotic platform is utilized for the
      procedure. In our experience, 12 women underwent robotic-assisted laparoscopic
      anterior pelvic exenteration and extracorporeal urinary diversion for clinically
      localized bladder cancer. RESULTS: Mean age was 67.9 years (range 61-79 years).
      Nine patients underwent ileal conduit diversion and three patients underwent an
      orthotopic neobladder. In all cases, the urinary diversion was performed
      extracorporeally. Mean operating room time was 4.6 h; mean surgical blood loss
      was 221 mL. On surgical pathology, seven patients were =pT2, three patients were
      pT3, and two patients were N+. In no case was there positive surgical margins,
      and in one case there was inadvertent entry into the bladder. Mean number of
      lymph nodes removed was 19 (range 12-34). Mean time to flatus was 1.9 days and to
      bowel movement 2.4 days, and time to discharge 4.8 days. Six patients were
      discharged on postoperative day 4, four patients on postoperative day 5, one on
      postoperative day 6, and one on postoperative day 8. There were two postoperative
      complications (17%) in two patients. CONCLUSIONS: Our initial experience with
      robotic-assisted laparoscopic anterior pelvic exenteration appears to be
      favorable with acceptable operative, pathologic, and short-term clinical
      outcomes. Certainly, larger experiences are required to adequately evaluate and
      validate this procedure as an appropriate surgical and oncologic option.

PMID- 18620503
TI  - Laparoscopic management of genitourinary hydatid cyst disease.
AB  - Hydatid disease is endemic in parts of India. Genitourinary involvement is rare.
      Laparoscopic management of such cases is uncommonly reported. We present our
      experience of laparoscopic management of two cases of retrovesical hydatid cyst
      treated by laparoscopic aspiration, instillation, and suction and two cases of
      renal hydatid cyst treated by partial nephrectomy and cystopericystectomy with
      preservation of renal parenchyma.

PMID- 18620504
TI  - The effect of cryoablation on the histologic interpretation of intraoperative
      biopsy of small clear cell renal carcinoma and renal oncocytoma.
AB  - BACKGROUND AND PURPOSE: We evaluated the effects of the first freeze-thaw cycle
      of cryoablation on Fuhrman grade, histology, and tumor architecture of small
      clear cell renal carcinomas and renal oncocytomas using an 18-gauge needle
      biopsy. PATIENTS AND METHODS: Between August 2006 and June 2007, 11 patients
      underwent cryoablation for 14 renal neoplasms. A laparoscopic approach was
      employed using third-generation argon/helium cryotechnology. Biopsies were taken
      prior to and following the first freeze-thaw cycle. Each biopsy sample was
      semiquantitively evaluated for cytoplasmic fraying, nuclear hyperchromasia,
      nuclear breakdown, and tissue discohesion as well as Fuhrman grade and
      interpretability by a single pathologist. RESULTS: Eighteen precryoablation and
      15 post-first freeze biopsies were taken. A tissue diagnosis was rendered in 100%
      of 11 patients. Pathologic diagnosis following the first freeze-thaw cycle of
      cryotherapy, as compared with the pretreatment biopsy, was accurate in 10 (91%)
      cases. Neither of the two post-first freeze biopsies in the remaining patient
      rendered a diagnosis: one had an insufficient quantity of tissue and the second
      missed the tumor, abstracting benign renal tissue. There was no significant
      difference in cytoplasmic fraying (P = 0.30), nuclear hyperchromasia (P = 0.43),
      nuclear breakdown (P = 0.58), or tissue discohesion (P = 0.84) observed between
      biopsies taken before and after the first freeze-thaw cycle of cryoablation. In
      no case did we note a change in Fuhrman grade greater than 1. CONCLUSIONS: One
      cycle of cryoablation does not significantly alter the architecture or Fuhrman
      grade of biopsy tissue, thus allowing for another method to obtain sufficient
      histologic tissue when bleeding is minimal.

PMID- 18620505
TI  - Occupational noise exposure during endourologic procedures.
AB  - INTRODUCTION: Long-term noise exposure in the workplace is a known cause of
      hearing loss. There has been limited study on the potential harm related to shock
      wave lithotripsy (SWL) or intracorporeal devices on patients and operating room
      personnel. PATIENTS AND METHODS: We used a digital sound meter to measure decibel
      levels in the operating room during several endourologic procedures. The decibel
      levels were recorded during SWL (Storz SLX-F2), percutaneous nephrolithotomy
      using single- and dual-probe ultrasonic lithotripters (Olympus LUS-2, CyberWand),
      and during ureteroscopy using the Versa Pulse Holmium:YAG laser. Findings were
      compared with the U.S. Department of Labor Occupational Health and Safety
      Administration and Canadian Centre for Occupational Health recommendations on
      permissible noise levels in the workplace. RESULTS: The background sound level in
      the operating room prior to endourologic procedures ranged between 58 and 60 dB.
      In the SWL control room, 5 m from the source, the mean sound level was 68 dB
      (range 64-75) during treatment. The mean corresponding decibel level recorded at
      the patient's head during SWL was 77 dB (range 73-83). Noises produced by
      intracorporeal lithotripters were recorded at the surgeon's head, 2 m from the
      source. Measurements of the CyberWand (dual-probe) device revealed a higher mean
      decibel reading of 93 dB (range 85-102). Noise levels recorded for the Olympus
      LUS-2 (single-probe) ultrasound and the holmium laser were 65 dB (62 -68) and 60
      dB (58-62), respectively. CONCLUSION: Although we noted that patients and
      urologists maybe exposed to significant noise levels during endourologic
      procedures, the duration of exposure is short. This risk appears to be minimal,
      based on current occupational guidelines, for most operating personnel.

PMID- 18620506
TI  - Working tools in flexible ureterorenoscopy--influence on flow and deflection:
      what does matter?
AB  - INTRODUCTION: Flexible renoscopes offer access to almost all points within the
      collecting system. For stone workup, excellent visualization is mandatory.
      Therefore, irrigation flow is of critical importance. The aim of this study was
      to evaluate the effect of tools and probes on deflection angle and irrigation
      flow volume in the latest generation of flexible renoscopes. METHODS: Five
      flexible renoscopes [Wolf (Viper), Storz (FlexX(2)), ACMI (DUR-8 Elite, DUR-D),
      Olympus (URF-P5)] were tested. Deflection angle, lowest diameter of the bent tip,
      and flow rates were measured. Recorded parameters were deflection angle and flow
      rate of the empty and loaded scopes. A laser probe (273 mum), biopsy forceps (2.4
      3.0 French), and tipless nitinol baskets (1.5-2.4 French) were tested. RESULTS:
      Deflection has no influence on flow rate. The size of the basket has no influence
      on the maximum angle of deflection. Introducing the laser fiber or the biopsy
      forceps leads to relevant loss of deflection (laser fiber: 4.44%-10.21%; biopsy
      forceps: 30.7%-57.8%). The inner diameter of the bent tip increases with
      introduction of a laser fiber (+1 to 3 mm) or the biopsy forceps (+13 to 34 mm).
      Flow rates are dependent on the size of the tool used. Loss of irrigation volume
      varies from 62.24% (1.5 French) to 99.1% (3.0 French). The use of a laser fiber
      leads to a decrease in irrigation volume of 53.7%. CONCLUSION: Irrigation flow,
      loss of deflection, and intraoperative visualization are dependent on the working
      tool used. The provided data, in awareness of the patient's anatomy, help to
      select scopes, probes, and tools correctly for successful ureterorenoscopy.

PMID- 18620507
TI  - Laparoscopic port-site metastasis in urologic surgery.
AB  - PURPOSE: Port-site metastasis has been an increasing concern with the spread of
      laparoscopy in managing urologic malignancies. The purpose of this study was to
      provide a current review of port-site metastases reported in the urologic
      oncology literature, as well as etiologic factors and preventative measures.
      METHODS: A comprehensive Medline search (up to September 2007; subject headings:
      "neoplasm seeding," "laparoscopy," "urologic neoplasms") of all case reports and
      series related to laparoscopic urology surgery for malignant disease was
      performed. The references for each of these case reports and series were also
      reviewed for any additional reports of port-site metastases. RESULTS: Only 28
      cases of port-site metastases involving urologic malignancies have been reported,
      with laparoscopic procedures involving upper tract transitional cell carcinoma
      comprising the majority (11/28 or 39%) of these. Recent reports involving renal
      cell carcinoma, prostatic carcinoma, and bladder cancer have been published as
      well. SUMMARY: The incidence of port-site metastases is comparable with that seen
      following open surgery. The etiology is likely multifactorial, but adhering to
      proper surgical technique is the most effective preventative strategy.

PMID- 18620508
TI  - Molecular screening of Bartonella species in rodents from south western Spain.
AB  - Rodents (87 Mus spretus and 10 Rattus norvegicus) collected in a suburban area of
      Seville (Andalusia, Spain) between September 2003 and April 2004 were tested by
      polymerase chain reaction for the presence of Bartonella DNA using primers
      amplifying a fragment of the 16S/23S rRNA internal transcribed spacer (ITS).
      Sequence analyses of the ITS of these Bartonella demonstrated that rodents in
      this region harbored at least three strains: two Bartonella genotypes detected in
      M. spretus, which clustered separately, and one genotype corresponding with B.
      tribocorum in R. norvegicus. The finding of Bartonella species in a high
      proportion of the rodent samples suggests the need to investigate whether these
      agents might be responsible for cases of febrile illnesses of unknown etiology in
      Southern Spain.

PMID- 18620509
TI  - Density-dependent competitive suppression of sylvatic dengue virus by endemic
      dengue virus in cultured mosquito cells.
AB  - Mosquito-borne dengue viruses are maintained in two discrete transmission cycles:
      a sylvatic cycle between nonhuman primates and sylvatic Aedes mosquitoes, and an
      endemic cycle between humans and peridomestic Aedes (primarily Ae. aegypti and
      Ae. albopictus). Most sylvatic strains are genetically distinct from endemic
      strains, and human infections with sylvatic strains have been detected only
      rarely. Interestingly, sylvatic strains replicate as well as endemic strains in
      Ae. aegypti and experimental models of replication in humans, suggesting that
      adaptive constraints may not explain the limited spillover of sylvatic strains
      into the endemic cycle. Within-host competition is another mechanism known to
      decrease emergence of strains into occupied niches. In the current study, we
      examined the magnitude of competitive suppression between sylvatic and endemic
      dengue strains of different serotypes in pair-wise mixed infections of cultured
      Ae. albopictus cells to test whether the ecotype or the initial ratio of the two
      strains influenced the outcome of competition. Strains isolated from nonhuman
      primates were competitively inferior to those isolated from humans. Moreover,
      competition was density-dependent; the magnitude of suppression increased as the
      starting density of a strain relative to its competitor decreased. These data
      suggest that competitive inferiority in endemic vectors coupled with a numerical
      disadvantage relative to resident endemic strains could restrict reemergence of
      sylvatic strains into the endemic cycle and contribute to the ecologically
      correlated genetic divergence between sylvatic and endemic strains.

PMID- 18620510
TI  - Potential vectors of Rift Valley fever virus in the Mediterranean region.
AB  - We evaluated the ability of three mosquito species (Aedes caspius, Aedes
      detritus, Culex pipiens), collected in southern France and Tunisia, and of
      different laboratory-established colonies (Aedes aegypti, Aedes albopictus, Aedes
      vexans, Anopheles gambiae, Culex pipiens, Culex quinquefasciatus) to disseminate
      two strains of Rift Valley fever virus (RVFV), the virulent ZH548 and the
      avirulent Clone 13. After feeding on an infectious blood meal at 10(8.5) plaque
      forming units/mL, females were maintained at 30 degrees C for 14 days. Surviving
      females were tested for the presence of virus on head squashes. Disseminated
      infection rate corresponds to the number of females with disseminated infection
      among surviving females. Among field-collected mosquitoes, Cx. pipiens was the
      most susceptible species with disseminated infection rates ranging from 3.9% to
      9.1% for French strains and up to 14.7% for Tunisian strains. Among laboratory
      established colonies, Ae. aegypti from Tahiti exhibited the highest disseminated
      infection rates: 90% when infected with ZH548 and 72.6% with Clone 13. The
      presence of competent Cx. pipiens in southern France and Tunisia indicates the
      potential for RVFV epizootics to occur if the virus was introduced into countries
      of the Mediterranean basin.

PMID- 18620511
TI  - On chikungunya acute infection and chloroquine treatment.
AB  - In recent issues, the efficacy of chloroquine (and the dosage that may be used)
      in the treatment of acute chikungunya infections was discussed. We have conducted
      a double-blind placebo-controlled randomized trial on the French Reunion Island
      (Indian Ocean), in which 27 patients received chloroquine and 27 patients
      received a placebo treatment. The chloroquine treatment consisted of 600 mg at
      day 1, 600 mg at days 2 and 3, and 300 mg at days 4 and 5. No significant
      difference between groups could be identified regarding the duration of febrile
      arthralgia or the decrease of viremia between day 1 and day 3. However, at day
      200, patients who received chloroquine complained more frequently of arthralgia
      than those who received placebo (p < 0.01). In conclusion, our results suggest
      that there is currently no justification for the use of chloroquine to treat
      acute chikungunya infections.

PMID- 18620512
TI  - Dynamics and distribution of house infestation by Triatoma dimidiata in central
      and southern Belize.
AB  - Chagas disease is a major public health problem from South America to Mexico,
      with approximately 10 million infected people. Chagas disease is known to occur
      in Belize, but little is known about the prevalence of Trypansoma cruzi infection
      in the Belizean population or the Chagas vector in this region. An entomologic
      survey of triatomines in the central and southern region of Belize was thus
      performed. Triatomines were collected by community participation in 37 villages
      of the Cayo (central) and Toledo (southern) districts and analyzed for infection
      with T. cruzi by microscopic examination and polymerase chain reaction. Two
      hundred fifty-six triatomines were collected in 34/37 villages, indicating a wide
      distribution, and all were identified as T. dimidiata. The majority (87%) were
      adults (42% males, 58% females), and 13% were larval stages. The infection rate
      with T. cruzi was 28%. Triatomines were more abundant during the hot season
      (March-July) compared with the cooler season (September-February). These results
      confirm that there is a significant risk for autochthonous Chagas disease
      transmission in central and southern Belize and suggest a pattern of seasonal
      infestation by nondomiciliated adult triatomines, which are likely to be closely
      related to T. dimidiata from Yucatan, Mexico. Further entomologic and
      epidemiologic studies should be performed to precisely determine T. cruzi
      transmission risk to humans, as well as the seroprevalence of T. cruzi infection
      and incidence of Chagasic cardiomyopathy in the Belizean population.

PMID- 18620513
TI  - Nutritional stress affects mosquito survival and vector competence for West Nile
      virus.
AB  - Most anautogenous female mosquitoes ingest plant carbohydrates for flight energy
      and survival, and they imbibe vertebrate blood for egg development. We evaluated
      the effect of different sucrose meals following a blood meal containing West Nile
      virus (WNV) on Culex pipiens pipiens survival, nutritional status, and
      susceptibility to viral infection and transmission. Ten days after blood feeding,
      no mosquitoes survived on distilled water, 55% survived on 2% sucrose, 61% on 10
      and 20% sucrose meals, and over 70% survived on 40% sucrose. There was a positive
      correlation between sucrose meal concentration and detectable sugars, glycogen,
      and lipid in whole-body homogenates. Average sugar values increased from 0 microg
      per starved mosquito (range 0-1.0 microg) to an average of 392 microg per
      mosquito fed on 40% sucrose (85-1088 microg). Average glycogen values increased
      from 0 microg (0-5.7 microg) to an average of 620 microg (118-1421 microg).
      Average lipid values were identical for mosquitoes in the starved and 2% sucrose
      series (38 microg) and increased to 172 microg per mosquito fed on 40% sucrose
      (92-266 microg). Mosquitoes in all sucrose series were equally susceptible to WNV
      infection (p > 0.5), but mosquitoes with lower nutrient reserves as a result of
      lower sucrose meals were more likely to orally transmit virus (p < 0.05). We
      discuss how mosquito nutritional status influences probability of daily survival,
      susceptibility to infection, and vectorial capacity. We conclude that maintaining
      C. p. pipiens on standard 10% sucrose is justified in light of these results.

PMID- 18620514
TI  - Rickettsia slovaca infection in humans in the northeast of Spain: seroprevalence
      study.
AB  - Catalonia is an endemic area of Mediterranean spotted fever. In 1997, A. Lakos
      described a new tick-borne infectious disease called tick-borne lymphadenopathy.
      The causative agent is Rickettsia slovaca, which is transmitted by Dermacentor
      marginatus ticks. We have diagnosed human cases in Catalonia. The objective of
      this study was to determinate seroprevalence of R. slovaca infection in humans in
      the northeast of Spain. The population included 217 subjects from Catalonia,
      northeast of Spain and was stratified by age and living place (rural, suburban,
      and urban). Age, gender, residence area, contact with animals, occupation, and
      history of rickettsioses was surveyed. Immunoglobulin G was measured by indirect
      immunofluorescence assay. Titers >or= 1/40 were considered. Seroprevalence of R.
      slovaca was 5.5% at titers of 1/40-1/320. Eight (3.7%) sera had antibodies
      against R. slovaca exclusively. Four sera reacted also against Rickettsia conorii
      and/or Bar29. Seroprevalence of R. slovaca would range from 3.7% to 5.5%. The
      only statistically significant association was that between R. slovaca
      seropositivity and age. We present serologic evidence of R. slovaca infection
      among population of Catalonia, northeast of Spain.

PMID- 18620515
TI  - Relationship between plasma osteopontin and oxidative stress in patients with
      coronary artery disease.
AB  - BACKGROUND: It is known that oxidative stress plays an important role in the
      pathogenesis of atherosclerosis and that an association exists between
      osteopontin (OPN) and atherosclerosis. OBJECTIVES: It was proposed that
      malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress,
      would be related to plasma OPN levels in patients with coronary artery disease
      (CAD). METHODS/RESULTS: Plasma OPN and MDA levels were measured in 71 patients
      (60 males and 11 females; mean age 61.7 +/- 10 years). Fifty-eight patients had
      significant CAD (group I) and 13 patients were free of CAD as defined
      angiographically (group II). Plasma OPN was measured by enzyme-linked
      immunosorbent assay (ELISA), while MDA was determined spectrophotometrically.
      Multivariate regression analysis revealed that ln-transformed OPN levels were
      independently associated with MDA after adjustment for age, hypertension and
      diabetes mellitus (R(2) = 0.278, p = 0.0004 and beta regression coefficient =
      0.252 [standard error = 0.0958], p = 0.011). OPN and MDA levels were higher in
      patients with diabetes (73.6 +/- 36.2 ng/ml versus 56.1 +/- 30.9 ng/ml, p = 0.02
      and 2.5 +/- 0.5 microM versus 2.0 +/- 0.5 microM, p = 0.002, respectively).
      CONCLUSIONS: The association between OPN and MDA levels in patients with CAD
      suggests an interaction between OPN and oxidative stress. This interaction may
      play a role in the pathogenesis of atherosclerosis.

PMID- 18620516
TI  - MK2: a novel molecular target for anti-inflammatory therapy.
AB  - BACKGROUND: Mitogen-activated protein kinase (MAPK)-activated protein kinase 2
      (MK2) is activated upon stress by p38 MAPK. MK2 is stimulated in a wide range of
      inflammatory conditions and its catalytic activity is required for cytokine
      production, cell migration and is a potential drug target for inflammatory
      diseases. Disruption of MK2 leads to a reduction in TNF-alpha production. MK2
      mediated pro-inflammatory cytokine production has been demonstrated in several
      inflammatory conditions where TNF-alpha plays a role. OBJECTIVE/METHODS: We
      discuss the development of specific MK2 inhibitors for the treatment of
      inflammatory diseases. RESULTS/CONCLUSION: Inhibition of the p38 MAPK pathway may
      have therapeutic uses for inflammatory diseases. However, blocking p38 MAPK
      activation in vivo is not advisable due to toxicity, significant off-target
      effects, and lack of oral bioavailability. This concern may be countered by the
      use of MK2 inhibitors that can dissect the pathways downstream of p38 without
      affecting additional cellular functions.

PMID- 18620517
TI  - Cholesterol ester transfer protein: a therapeutic target in atherosclerosis?
AB  - BACKGROUND: CETP has an established role in the transport of cholesterol from the
      peripheral tissues to the liver for elimination. The fact that CETP was
      recognized as a target for raising high-density lipoprotein cholesterol (HDL-C)
      levels has led to research on CETP inhibitors to protect against atherosclerosis.
      OBJECTIVE: To review the role of CETP as a pivotal target for atherosclerosis and
      cardiovascular diseases and the effect of its overexpression or inhibition on
      lipid metabolism. METHODS: A review of literature on the role of CETP in
      cholesterol metabolism and on recent developments on CETP inhibitors.
      RESULTS/CONCLUSIONS: Animal and human studies have provided evidence supporting
      both the pro- and antiatherogenic roles of CETP. Clinical trials with CETP
      inhibitors remain under serious consideration. Further studies are necessary for
      understanding of the role of CETP in lipid metabolism and the development of
      novel therapies involving a combination of strategies for treatment of
      atherosclerosis and cardiovascular disease.

PMID- 18620518
TI  - Treatment of autism spectrum disorders: neurotransmitter signaling pathways
      involved in motivation and reward as therapeutic targets.
AB  - BACKGROUND: There is a growing body of literature describing the etiology of
      autism spectrum disorders (ASD). Some of the targets suggested belong to
      neurochemical transmitter pathways implicated in the behavior and motivation
      reward pathway. OBJECTIVE: To examine data linking potential targets to ASD and
      the feasibility of developing drugs targeting these pathways. While the
      inhibitors are mostly being developed for other indications, it is beneficial to
      examine them to determine the responsiveness of the targets to small-molecule
      modulation. METHODS: A search in Medline and Scifinder for articles concerning
      relevant targets in the context of ASD and their relation to the reward signaling
      pathway. RESULTS: There is evidence suggesting that behaviors controlled by these
      targets are related to behaviors exhibited by individuals with ASD. The targets
      appear to be involved in neurotransmitter pathways controlling motivation and
      reward, further implicating this system in ASD. Sufficient research has been
      conducted to identify lead compounds for discovering agents for treatment of ASD.

PMID- 18620519
TI  - Signaling through CD80: an approach for treating lymphomas.
AB  - BACKGROUND: One of the mechanisms by which tumors evade the immune system is by
      downregulating the expression of costimulatory molecules like CD80 and CD86. The
      role of CD80 in the activation of T cells is well established, and current
      studies are exploring its role in cancer. OBJECTIVE: To examine the possible role
      of CD80 signaling in generating an effective immune response against cancer
      cells. METHODS: Many reports have described the influence of CD80 on the growth
      of B cell and follicular lymphomas. Signaling through CD80 in B cell lymphomas
      can retard their proliferation by upregulating expression of pro-apoptotic
      molecules and downregulating antiapoptotic molecules and can therefore induce
      apoptosis. Recently, a Phase I/II study of treatment with CD80-specific antibody
      has shown it to be quite effective in relapsed and refractory follicular lymphoma
      patients. CONCLUSION: This study shows that anti-CD80 immunotherapy may have a
      potent role in treating CD80-bearing cancer cells.

PMID- 18620520
TI  - IAPs as therapeutic targets in haematological malignancies.
AB  - BACKGROUND: Regulation of apoptosis is fundamental to maintain the balance
      between cell survival and cell death. Disruption of this process may have severe
      consequences, contributing to carcinogenesis. Therapeutic targeting of the
      proteins that control apoptosis may therefore be used in the treatment of various
      types of cancer. OBJECTIVE: We address whether regulators of apoptosis could be
      suitable targets for the treatment of haematological cancers. METHODS: We focus
      on the emerging role of inhibitor of apoptosis (IAP) proteins in cancer, their
      modulators and the possibility of therapeutically targeting these proteins in
      haematological cancer. RESULTS/CONCLUSION: IAPs have emerged as an important
      novel class of intracellular proteins that regulate apoptosis. Various compounds
      have been described that may be used to modulate the activity of IAPs, which
      opens the way to therapeutically targeting these proteins in cancer.

PMID- 18620521
TI  - Netrin-1 and its receptors in tumour growth promotion.
AB  - BACKGROUND: Netrin-1 belongs to a family of secreted proteins that act as
      migration and adhesion cues in the developing CNS and in a number of non-neural
      tissues. Netrin-1 is the ligand of deleted in colorectal cancer (DCC) and the
      uncoordinated family member 5 (UNC5) orthologues of the dependence receptor
      family. Over the past ten years, a novel mechanism has emerged, that a receptor
      unoccupied by its ligand is not necessarily inactive. Rather, such a receptor can
      mediate two signalling pathways, depending on whether it is bound to its ligand
      or not. In the absence of ligand, an active signalling pathway results in cell
      death through apoptosis. OBJECTIVE: Coupled netrin-1 receptors have been shown to
      regulate diverse processes such as maintenance, integrity, migration and renewal
      of many tissues. We propose that netrin-1 receptors can regulate tumour
      development. METHODS: We review the properties of netrin-1 and present netrin-1
      receptors as regulators of tumourigenesis. RESULTS/CONCLUSION: Netrin-1 and its
      receptors are unexplored critical targets in cancer.

PMID- 18620522
TI  - Downregulating sphingosine kinase-1 for cancer therapy.
AB  - BACKGROUND: The sphingolipids ceramide and sphingosine 1-phosphate (S1P) are key
      regulators of cell death and proliferation. The subtle balance between their
      intracellular levels is governed mainly by sphingosine kinase-1, which produces
      the pro-survival S1P. Sphingosine kinase-1 is an oncogene; is overexpressed in
      many tumors; protects cancer cells from apoptosis in vitro and in vivo; and its
      activity is decreased by anticancer therapies. Hence, sphingosine kinase-1
      appears to be a target of interest for therapeutic manipulation. OBJECTIVE: This
      review considers recent developments regarding the involvement of sphingosine
      kinase-1 as a therapeutic target for cancer, and describes the pharmacological
      tools currently available. RESULTS/CONCLUSION: The studies described provide
      strong evidence that strategies to kill cancer cells via sphingosine kinase-1
      inhibition are valid and could have a favorable therapeutic index.

PMID- 18620524
TI  - DNA methylation: a promising target for the twenty-first century.
AB  - BACKGROUND: Over the last few years DNA methylation and its involvement in
      diseases such as cancer has become of great interest for applied research. Since
      reversal of aberrant DNA methylation may influence the behavior of tumors, the
      methylation of DNA CpG sites is a potential target for the development of
      inhibitors for use in cancer treatment. OBJECTIVE/METHODS: We briefly review the
      structural and mechanistic features of DNA methylation, including a structural
      analysis of the three main human DNA methyltransferases and some (pre)clinical
      results. RESULTS/CONCLUSION: Despite side effects, data obtained to date still
      support the vision that DNA-methylation, possibly associated with the use of
      histone deacetylases (HDACs) and/or artificial transcription factors (ATFs), is a
      promising target for improving anticancer therapy in the 21st century.

PMID- 18620523
TI  - Grb2 signaling in cell motility and cancer.
AB  - BACKGROUND: Metastasis is the primary cause of death in most human cancers, and
      understanding the molecular mechanisms underpinning this multistep process is
      fundamental to identifying novel molecular targets and developing more effective
      therapies. OBJECTIVE/METHODS: Here we review the role of growth factor receptor
      bound protein 2 (Grb2) in cancer and specifically in metastasis-related
      processes, and summarize the development of anticancer therapeutics selectively
      targeting this adapter protein. RESULTS/CONCLUSION: Grb2 is a key molecule in
      intracellular signal transduction, linking activated cell surface receptors to
      downstream targets by binding to specific phosphotyrosine-containing and proline
      rich sequence motifs. Grb2 signaling is critical for cell cycle progression and
      actin-based cell motility, and, consequently, more complex processes such as
      epithelial morphogenesis, angiogenesis and vasculogenesis. These functions make
      Grb2 a therapeutic target for strategies designed to prevent the spread of solid
      tumors through local invasion and metastasis.

PMID- 18620525
TI  - PPAR-gamma signaling pathway in placental development and function: a potential
      therapeutic target in the treatment of gestational diseases.
AB  - BACKGROUND: PPAR-gamma is a target for the treatment of metabolic disorders, as
      Pioglitazone and Rosiglitazone are already used against type 2 diabetes.
      Pleiotropic functions, such as antiproliferative and anti-inflammatory effects
      against several pathological states, including cardiovascular disease and cancer,
      are currently being explored in clinical studies. OBJECTIVE: Evidence indicates
      that PPAR-gamma is expressed in the placenta, playing a crucial role in placental
      development and function, while PPAR-gamma ligands appear to modulate fetal
      membrane signals. Thus, in the last few years, the pivotal role of PPAR-gamma in
      placental biology has been the focus of extensive research, as diabetes appears
      to be the most common metabolic dysfunction in pregnancy. METHODS: We aim to
      present data concerning the expression of PPAR-gamma in animal and human
      placenta, underlining its significance in normal placental development and
      several gestational diseases. The effects of PPAR-gamma ligands as modulators of
      placental biology in normal and certain pathological conditions are also
      discussed. RESULTS/CONCLUSION: Current research provides substantial evidence
      that PPAR-gamma plays a pivotal role in placental biology and may reveal new
      perspectives in the treatment of gestational diseases.

PMID- 18620526
TI  - Use of LHRH-agonists as adjuvant therapy for breast cancer.
AB  - Individual data was collected for 11,906 women in 16 randomised trials evaluating
      a luteinising-hormone-releasing hormone (LHRH) agonist either alone, as an
      addition to tamoxifen or chemotherapy or in place of chemotherapy. When used
      alone these agents led to a large (28%) relative decrease in recurrence, which
      was not significant (p = 0.08) due to the small number of patients randomised.
      Addition of LHRH-agonist to tamoxifen, chemotherapy or both, reduced recurrence
      by 13% (p = 0.02), and when used alone these agents showed similar efficacy to
      chemotherapy. The largest effect after chemotherapy was seen in women aged <or=
      40 years. Most of the chemotherapy was CMF-based, so comparisons with more modern
      chemotherapy would be useful. In addition, the optimum duration of treatment is
      unknown.

PMID- 18620527
TI  - Role of glyceraldehyde-3-phosphate dehydrogenase in vesicular transport from
      golgi apparatus to endoplasmic reticulum.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a well-studied glycolytic
      protein with energy production as its implied occupation. It has established
      itself lately as a multifunctional protein. Recent studies have found GAPDH to be
      involved in a variety of nuclear and cytosolic pathways ranging from its role in
      apoptosis and regulation of gene expression to its involvement in regulation of
      Ca2+ influx from endoplasmic reticulum. Numerous studies also indicate that GAPDH
      interacts with microtubules and participates in cell membrane fusion. This review
      is focused on the cytosolic functions of the protein related to vesicular
      transport. Suggestions for future directions as well as the model of protein
      polymer structure and possible post-translational modifications as a basis for
      its multifunctional activities in the early secretory pathway are given.

PMID- 18620528
TI  - The centrosome is a polyfunctional multiprotein cell complex.
AB  - Contemporary knowledge about centrosome proteins and their ensembles, which can
      be divided into several functional groups--microtubule-nucleating proteins,
      microtubule-anchoring proteins, centriole-duplication proteins, cell cycle
      control proteins, primary cilia growth regulation proteins, and proteins of
      regulation of cytokinesis--is reviewed. Structural-temporal classification of
      centrosomal proteins and the scheme of interconnection between the different
      centrosomal protein complexes are presented.

PMID- 18620529
TI  - Analysis of proteins interacting with TRIP8b adapter.
AB  - Calcium-independent receptor of latrotoxin (CIRL) is an orphan heptahelical
      receptor implicated in regulation of exocytosis. To characterize molecular
      mechanisms of CIRL functioning, we searched for its intracellular partners using
      the yeast two-hybrid SR system with the cytoplasmic C-terminal fragment of CIRL
      as bait. One of the interacting proteins was identified as TRIP8b, a putative
      cytosolic adapter protein with multiple tetratricopeptide repeats. To understand
      functional significance of CIRL-TRIP8b interaction, we further isolated TRIP8b
      interacting proteins by affinity chromatography of brain extracts on immobilized
      recombinant TRIP8b. Sixteen proteins were identified by mass spectrometry in the
      purified preparations. Clathrin and subunits of AP2 complex appeared to be the
      major TRIP8b-interacting proteins. Our data suggest a role of TRIP8b in receptor
      mediated endocytosis.

PMID- 18620530
TI  - Selection of random RNA fragments as method for searching for a site of
      regulation of translation of E. coli streptomycin mRNA by ribosomal protein S7.
AB  - In E. coli cells ribosomal small subunit biogenesis is regulated by RNA-protein
      interactions involving protein S7. S7 initiates the subunit assembly interacting
      with 16S rRNA. During shift-down of rRNA synthesis level, free S7 inhibits self
      translation by interacting with 96 nucleotides long specific region of
      streptomycin (str) mRNA between cistrons S12 and S7 (intercistron). Many bacteria
      do not have the extended intercistron challenging development of specific
      approaches for searching putative mRNA regulatory regions, which are able to
      interact with proteins. The paper describes application of SERF approach
      (Selection of Random RNA Fragments) to reveal regulatory regions of str mRNA. Set
      of random DNA fragments has been generated from str operon by random hydrolysis
      and then transcribed into RNA; the fragments being able to bind protein S7
      (serfamers) have been selected by iterative rounds. S7 binds to single serfamer,
      109 nucleotide long (RNA109), derived from the intercistron. After multiple
      copying and selection, the intercistronic mutant (RNA109) has been isolated; it
      has enhanced affinity to S7. RNA109 binds to the protein better than authentic
      intercistronic str mRNA; apparent dissociation constants are 26 +/- 5 and 60 +/-
      8 nM, respectively. Location of S7 binding site on the mRNA, as well as putative
      mode of regulation of coupled translation of S12 and S7 cistrons have been
      hypothesized.

PMID- 18620531
TI  - Hepatitis C virus helicase/NTPase: an efficient expression system and new
      inhibitors.
AB  - A method has been developed for obtaining a full-length protein NS3 of hepatitis
      C virus with the yield of 6.5 mg/liter of cell culture, and conditions for
      measuring its NTPase and helicase activities have been optimized. The helicase
      reaction can proceed in two modes depending on the enzyme and substrate
      concentration ratio: it can be non-catalytic in the case of enzyme excess and
      catalytic in the case of tenfold substrate excess. In the latter case, helicase
      activity is coupled with NTPase and is stimulated by ATP. A number of NTP and
      inorganic pyrophosphate analogs were studied as substrates and/or inhibitors of
      NS3 NTPase activity, and it was found that the structure of nucleic base and
      ribose fragment of NTP molecule has a slight effect on its inhibitory (substrate)
      properties. Among the nucleotide derivatives, the most efficient inhibitor of
      NTPase activity is 2 -deoxythymidine 5 -phosphoryl-beta,gamma-hypophosphate, and
      among pyrophosphate analogs imidodiphosphate exhibited maximal inhibitory
      activity. These compounds were studied as inhibitors of the helicase reaction,
      and it was shown that imidodiphosphate efficiently inhibited the ATP-dependent
      helicase reaction and had almost no effect on the ATP-independent duplex
      unwinding. However, the inhibitory effect of 2 -deoxythymidine 5 -phosphoryl
      beta,gamma-hypophosphate was insignificant in both cases, which is due to the
      possibility of helicase activation by this ATP analog.

PMID- 18620532
TI  - Anti-inflammatory activity of polysaccharide from Pholiota nameko.
AB  - Pholiota nameko polysaccharide (PNPS-1) has been isolated and purified by
      enzymatic hydrolysis, hot water extraction, ethanol precipitation, and ion
      exchange and gel-filtration chromatography. The anti-inflammatory activity of
      PNPS-1 was evaluated in rodents using xylene-induced ear edema, egg albumin-,
      carrageenin-, and formaldehyde-induced paw edema, cotton pellet granuloma test,
      adhesion of peritoneal leukocytes in vitro, and ulcerogenic activity. The results
      showed that PNPS-1 (5 mg/ear) inhibited topical edema in the mouse ear and at
      100, 200, and 400 mg/kg (intraperitoneally) it significantly suppressed the
      development of egg albumin-, carrageenin-, and formaldehyde-induced paw edema in
      the animals. PNPS-1 (100, 200, and 400 mg/kg, per oral) significantly inhibited
      the growth of granuloma tissues induced by subcutaneously implanted cotton
      pellets in rats by 10.96, 18.07, and 43.75%, respectively. PNPS-1 also inhibited
      spontaneous and phorbol-12-myristate-13-acetate-activated adhesion of peritoneal
      leukocytes in vitro. Further, both acute as well as chronic administration of
      PNPS-1 (100, 200, and 400 mg/kg, per oral) did not produce any gastric lesion in
      rats. In conclusion, these data indicated that PNPS-1 possesses significant anti
      inflammatory activity suggesting its potential as an anti-inflammatory agent for
      use in the treatment of various inflammatory-related diseases.

PMID- 18620533
TI  - Proteomic characterization of royal jelly proteins in Chinese (Apis cerana
      cerana) and European (Apis mellifera) honeybees.
AB  - In this study, the proteins contained in royal jelly (RJ) derived from Chinese
      and European honeybees have been analyzed in detail and compared. Remarkable
      differences were found in the heterogeneity of major royal jelly proteins
      (MRJPs), MRJP2 and MRJP3, in terms of molecular weight and isoelectric points
      between the two species of RJ. MRJP2 and MRJP3 produced by Chinese honeybee are
      less polymorphic than those produced by European honeybee. This study is a
      contribution to the description of the royal jelly proteome.

PMID- 18620534
TI  - Coalescence of spherical beads of retro-HSP12.6 into linear and ring-shaped
      amyloid nanofibers.
AB  - The sequence-reversed form of a small heat shock protein, HSP12.6 (retro
      HSP12.6), has been reported to fold and assemble into structured tetramers in
      aqueous solution. Upon raising the protein concentration to ~1.0-1.5 mg/ml,
      tetrameric retro-HSP12.6 is known to display a tendency to associate further into
      spherical beads of 18-20 nm in diameter containing folded protein subunits. Here
      we report that storage of this protein at low temperatures leads to further
      association of the beaded structures into linear and ring-shaped amyloid
      nanofibers of 18-20 nm in diameter. The electron micrographs presented in this
      communication provide the best visual evidence yet that amyloids can form through
      the association of smaller structured bead-like intermediates. The results also
      suggest that folded beta-sheet-rich subunits can participate in amyloid
      formation.

PMID- 18620535
TI  - Molecular cloning and analysis of function of nucleoside diphosphate kinase
      (NDPK) from the scallop Chlamys farreri.
AB  - Nucleoside diphosphate kinase (NDPK) is a key metabolic enzyme that catalyzes the
      synthesis of non-adenine nucleoside triphosphate (NTP) by transferring the
      terminal phosphate between nucleoside diphosphate (NDP) and NTP. NDPK regulates a
      variety of eukaryotic cellular activities including cell proliferation,
      development, and differentiation. The ndpk cDNA was cloned from the hemocytes of
      the scallop Chlamys farreri and designated Cf-ndpk. The full-length sequence of
      Cf-ndpk consists of 715 bp encoding a polypeptide of 153 amino acids with a
      calculated molecular mass of 16927.52 daltons and pI of 7.64. The mRNA expression
      and distribution of Cf-ndpk in both bacterially challenged and unchallenged
      scallops were studied by Northern blotting and in situ hybridization. The results
      showed that Cf-ndpk transcripts were present in hemocytes, gill, adductor muscle,
      mantle, digestive gland, foot, and gonad, and the expression level increased in
      hemocytes after bacterial challenge. Recombinant Cf-NDPK expressed in Escherichia
      coli could transfer the terminal phosphate between UDP and ATP. The Cf-NDPK
      protein was present in all tested tissues including foot, adductor muscle,
      digestive gland, gonad, mantle, gill, and hemolymph. It was up-regulated in
      hemolymph after bacterial challenge. Taken together, these results suggest that
      NDPK may play roles in the innate immune response of scallop.

PMID- 18620536
TI  - pH-induced equilibrium unfolding of apomyoglobin: substitutions at conserved
      Trp14 and Met131 and non-conserved Val17 positions.
AB  - A number of residues in globins family are well conserved but are not directly
      involved in the primary oxygen-carrying function of these proteins. A possible
      role for these conserved, non-functional residues has been suggested in promoting
      a rapid and correct folding process to the native tertiary structure. To test
      this hypothesis, we have studied pH-induced equilibrium unfolding of mutant
      apomyoglobins with substitutions of the conserved residues Trp14 and Met131,
      which are not involved in the function of myoglobin, by various amino acids. This
      allowed estimating their impact on the stability of various conformational states
      of the proteins and selecting conditions for a folding kinetics study. The
      results obtained from circular dichroism, tryptophan fluorescence, and
      differential scanning microcalorimetry for these mutant proteins were compared
      with those for the wild type protein and for a mutant with the non-conserved
      Val17 substituted by Ala. In the native folded state, all of the mutant
      apoproteins have a compact globular structure, but are destabilized in comparison
      to the wild type protein. The pH-induced denaturation of the mutant proteins
      occurs through the formation of a molten globule-like intermediate similar to
      that of the wild type protein. Thermodynamic parameters for all of the proteins
      were calculated using the three state model. Stability of equilibrium
      intermediates at pH ~4.0 was shown to be slightly affected by the mutations.
      Thus, all of the above substitutions influence the stability of the native state
      of these proteins. The cooperativity of conformational transitions and the
      exposed to solvent protein surface were also changed, but not for the
      substitution at Val17.

PMID- 18620537
TI  - Single-chain antibody against human lipocalin-type prostaglandin D synthase:
      construction, expression, purification, and activity assay.
AB  - An active form of single-chain antibody (ScFv) from murine monoclonal antibody
      4A7, which is specific for lipocalin-type prostaglandin D synthase (L-PGDS), was
      produced in Escherichia coli. The complementary DNA fragments encoding the
      variable regions of heavy chain (VH) and light chain (VL), which amplified from
      hybridoma 4A7 producing a monoclonal antibody (IgG1) against L-PGDS, were
      connected by a (Gly4Ser)3 linker using an assembly polymerase chain reaction. The
      resultant ScFv were cloned into the vector pGEM and expressed in E. coli as
      inclusion bodies. The expressed ScFv fusion proteins were purified by Ni2+
      nitrilotriacetic acid chromatography. The purity and activity of purified ScFv
      were confirmed by SDS-PAGE and ELISA. The result revealed that 4A7 ScFv conserved
      the same characteristics of specific recognition and binding to sperm as the
      parental 4A7 monoclonal antibody.

PMID- 18620538
TI  - Interaction of human alpha-lactalbumin with fatty acids: determination of binding
      parameters.
AB  - The interaction of holo- and apo-forms of human alpha-lactalbumin with fatty
      acids was studied by a partition equilibrium method. Apo-alpha-lactalbumin,
      obtained by treatment with EDTA, displays one binding site for fatty acids, the
      association constants for oleic and palmitic acids being 1.9.10(6) and 4.2.10(5)
      M(-1), respectively. However, holo-alpha-lactalbumin was unable to bind fatty
      acids as measured by this technique. Likewise, no fatty acids bound to holo-alpha
      lactalbumin, isolated using nondenaturing conditions, were detected by gas
      chromatography. These results demonstrate that the conformational change induced
      in alpha-lactalbumin by the removal of calcium enables the protein to interact
      with fatty acids.

PMID- 18620539
TI  - Activated protein C via PAR1 receptor regulates survival of neurons under
      conditions of glutamate excitotoxicity.
AB  - The effect of an anticoagulant and cytoprotector blood serine proteinase-
      activated protein C (APC)--on survival of cultured hippocampal and cortical
      neurons under conditions of glutamate-induced excitotoxicity has been studied.
      Low concentrations of APC (0.01-10 nM) did not cause neuron death, but in the
      narrow range of low concentrations APC twofold and stronger decreased cell death
      caused by glutamate toxicity. High concentrations of APC (>50 nM) induced the
      death of hippocampal neurons similarly to the toxic action of glutamate. The
      neuroprotective effect of APC on the neurons was mediated by type 1 proteinase
      activated receptor (PAR1), because the inactivation of the enzyme with
      phenylmethylsulfonyl fluoride or PAR1 blockade by a PAR1 peptide antagonist
      ((Tyr1)-TRAP-7) prevented the protective effect of APC. Moreover, APC inhibited
      the proapoptotic effect of 10 nM thrombin on the neurons. Geldanamycin, a
      specific inhibitor of heat shock protein Hsp90, completely abolished the
      antiapoptotic effect of 0.1 nM APC on glutamate-induced cytotoxicity in the
      hippocampal neurons. Thus, APC at low concentrations, activating PAR1, prevents
      the death of hippocampal and cortical neurons under conditions of glutamate
      excitotoxicity.

PMID- 18620540
TI  - Analysis of RNA cleavage by RNA polymerases from Escherichia coli and Deinococcus
      radiodurans.
AB  - RNA polymerase can both synthesize and cleave RNA. Both reactions occur at the
      same catalytic center containing two magnesium ions bound to three aspartic acid
      residues of the absolutely conserved NADFDGD motif of the RNA polymerase beta
      subunit. We have demonstrated that RNA polymerase from Deinococcus radiodurans
      possesses much higher rate of intrinsic RNA cleavage than RNA polymerase from
      Escherichia coli (the difference in the rates is about 15-fold at 20 degrees C).
      However, these RNA polymerases do not differ in the rates of RNA synthesis.
      Comparison of the RNA polymerase sequences adjacent to the NADFDGD motif reveals
      the only amino acid substitution in this region (Glu751 in D. radiodurans vs.
      Ala455 in E. coli), which is localized in the secondary enzyme channel and can
      potentially affect the rate of RNA cleavage. Introduction of the corresponding
      substitution in the E. coli RNA polymerase leads to a slight (about 2-3-fold)
      increase in the cleavage rate, but does not affect RNA synthesis. Thus, the
      difference in the RNA cleavage rates between E. coli and D. radiodurans RNA
      polymerases is likely determined by multiple amino acid substitutions, which do
      not affect the rate of RNA synthesis and are localized in several regions of the
      active center.

PMID- 18620541
TI  - Mechanism of photoisomerization of the rhodopsin chromophore.
AB  - This work is devoted to the problem connected with rhodopsin activation.
      Electrostatic forces involved in photoisomerization of retinal are considered. It
      is suggested that the repulsion force and rotating moment between electric dipole
      moments of methyl groups on the C5 and C13 atoms of retinal can promote
      isomerization upon light absorption because the pi-pi* transition is accompanied
      by a decrease in the potential barrier for torsional rotations around the C11-C12
      bond.

PMID- 18620542
TI  - Structure-function relationships in Escherichia coli adenylate cyclase.
AB  - Class I adenylate cyclases are found in gamma- and delta-proteobacteria. They
      play central roles in processes such as catabolite repression in Escherichia coli
      or development of full virulence in pathogens such as Yersinia enterocolitica and
      Vibrio vulnificus. The catalytic domain (residues 2-446) of the adenylate cyclase
      of E. coli was overexpressed and purified. It displayed a V(max) of 665 nmol of
      cAMP x mg(-1) x min(-1) and a K(m) of 270 microM. Titration of the metal cofactor
      Mg(2+) against the substrate ATP showed a requirement for free metal ions in
      addition to the MgATP complex, suggesting a two-metal-ion mechanism as is known
      for class II and class III adenylate cyclases. Twelve residues which are
      essential for catalysis were identified by mutagenesis of a total of 20 polar
      residues conserved in all class I adenylate cyclases. Five essential residues
      (Ser(103), Ser(113), Asp(114), Asp(116) and Trp(118)) were part of a region which
      is found in all members of the large DNA polymerase beta-like
      nucleotidyltransferase superfamily. Alignment of the E. coli adenylate cyclase
      with the crystal structure of a distant member of the superfamily, archaeal tRNA
      CCA-adding enzyme, suggested that Asp(114) and Asp(116) are the metal-cofactor
      ion-binding residues. The S103A mutant had a 17-fold higher K(m) than wild-type,
      demonstrating its important role in substrate binding. In comparison with the
      tRNA CCA-adding enzyme, Ser(103) of the E. coli adenylate cyclase apparently
      binds the gamma-phosphate group of ATP. Consistent with this function, the S103A
      mutation caused a marked reduction of discrimination between ATP- and ADP- or AMP
      derived inhibitors.

PMID- 18620543
TI  - A novel neuronal calcium sensor family protein, calaxin, is a potential Ca(2+)
      dependent regulator for the outer arm dynein of metazoan cilia and flagella.
AB  - BACKGROUND INFORMATION: Spermatozoa show several changes in flagellar waveform,
      such as upon fertilization. Ca(2+) has been shown to play critical roles in
      modulating the waveforms of sperm flagella. However, a Ca(2+)-binding protein in
      sperm flagella that regulates axonemal dyneins has not been fully characterized.
      RESULTS: We identified a novel neuronal calcium sensor family protein, named
      calaxin (Ca(2+)-binding axonemal protein), in sperm flagella of the ascidian
      Ciona intestinalis. Calaxin has three EF-hand Ca(2+)-binding motifs, and its
      orthologues are present in metazoan species, but not in yeast, green algae or
      plant. Immunolocalization revealed that calaxin is localized near the outer arm
      of the sperm flagellar axonemes. Moreover, it is distributed in adult tissues
      bearing epithelial cilia. An in vitro binding experiment indicated that calaxin
      binds to outer arm dynein. A cross-linking experiment showed that calaxin binds
      to beta-tubulin in situ. Overlay experiments further indicated that calaxin binds
      the beta-dynein heavy chain of outer arm dynein in the presence of Ca(2+).
      CONCLUSIONS: These results suggest that calaxin is a potential Ca(2+)-dependent
      modulator of outer arm dynein in metazoan cilia and flagella.

PMID- 18620544
TI  - Identification of lysine residues critical for the transcriptional activity and
      polyubiquitination of the NF-kappaB family member RelB.
AB  - RelB is the key component of the alternative NF-kappaB (nuclear factor kappaB)
      signalling pathway. However, RelB exerts also a negative effect via the
      recruitment of a DNMT1 (DNA methyltransferase 1)-Daxx (death domain-associated
      protein) complex to NF-kappaB target genes. Importantly, the molecular mechanisms
      which determine the functions of RelB are still largely unknown. In the present
      study, we aimed to analyse whether ubiquitination of RelB might be involved in
      the regulation of RelB. Indeed, RelB is constitutively polyubiquitinated in the B
      cell lines Namalwa and 70Z/3. Although a PMA+ionomycin-induced augmentation of
      RelB polyubiquitination was linked to its proteasomal degradation in B-cells, the
      constitutive RelB polyubiquitination seems to affect non-proteasomal functions.
      Consistently, a significant RelB polyubiquitination in HEK (human embryonic
      kidney)-293 cells correlated with an augmentation of the transcriptional activity
      of RelB. Yet, neither nuclear localization nor DNA binding was enhanced by RelB
      polyubiquitination. Interestingly, basal RelB polyubiquitination depends neither
      on Lys(48) nor on Lys(63) conjugates, but might involve unconventional ubiquitin
      conjugates. Mapping of the ubiquitination target sites in RelB revealed the
      existence of various lysine residues, which serve as ubiquitination acceptors.
      However, only the substitution of Lys(273/274) and Lys(305/308) significantly
      decreased the basal RelB activity and the ubiquitin-induced augmentation of the
      RelB activity. Collectively, these results imply a dual role of RelB
      polyubiquitination for the stability and activity of this transcription factor.

PMID- 18620545
TI  - Identification and characterization of FUS/TLS as a new target of ATM.
AB  - ATM (ataxia-telangiectasia mutated), ATR (ATM- and Rad3-related) and DNA-PK (DNA
      dependent protein kinase), important regulators of genome stability, belong to
      the PIKK (phosphoinositide 3-kinase-like kinase) family of protein kinases. In
      the present study, DNA-affinity chromatography was used to identify DNA-binding
      proteins phosphorylated by these kinases. This resulted in the identification of
      FUS (fused in sarcoma)/TLS (translocated in liposarcoma) as an in vitro target of
      the PIKKs. FUS is a member of the Ewing's sarcoma family of proteins that appears
      to play a role in regulating genome stability, since mice lacking FUS show
      chromosomal instability and defects in meiosis. The residues in FUS that are
      phosphorylated in vitro and in vivo were identified, and phospho-specific
      antibodies were generated to demonstrate that FUS becomes phosphorylated at
      Ser(42) in vivo, primarily in response to agents that cause DSBs (double-strand
      breaks). DSB-induced FUS phosphorylation in vivo at Ser(42) requires ATM and not
      DNA-PK. Although Ser(42) is retained in the oncogenic FUS-CHOP [C/EBP
      (CCAAT/enhancer-binding protein)-homologous protein 10] fusion generated by a
      t(12;16)(q13;p11) chromosomal translocation, Ser(42) in FUS-CHOP is not
      phosphorylated after DNA damage. These results identify FUS as a new target of
      the ATM-signalling pathway and strengthen the notion that FUS regulates genome
      stability.

PMID- 18620546
TI  - Discovery of novel non-peptide thrombopoietin mimetic compounds that induce
      megakaryocytopoiesis.
AB  - We have identified a series of novel non-peptide compounds that activate the
      thrombopoietin-dependent cell line Ba/F3-huMPL. The compounds stimulated
      proliferation of Ba/F3-huMPL in the absence of other growth factors, but did not
      promote proliferation of the thrombopoietin-independent parent cell line Ba/F3.
      The thrombopoietin-mimetic compounds elicited signal-transduction responses
      comparable with recombinant human thrombopoietin, such as tyrosine
      phosphorylation of the thrombopoietin receptor, JAK (Janus kinase) 2, Tyk2
      (tyrosine kinase 2), STAT (signal transducer and activator of transcription) 3,
      STAT5, MAPKs (mitogen-activated protein kinases), PLCgamma (phospholipase
      Cgamma), Grb2 (growth-factor-receptor-bound protein 2), Shc (Src homology and
      collagen homology), Vav, Cbl and SHP-2 (Src homology 2 domain-containing protein
      tyrosine phosphatase 2) and increased the number of CD41(+) cells (megakaryocyte
      lineage) in cultures of human CD34(+) bone-marrow cells (haematopoietic stem
      cells). These findings suggest that this series of compounds are novel agonists
      of the human thrombopoietin receptor and are possible lead compounds for the
      generation of anti-thrombocytopaenia drugs.

PMID- 18620548
TI  - A possible biochemical link between NADPH oxidase (Nox) 1 redox-signalling and
      ERp72.
AB  - Emerging evidence indicates that Nox (NADPH oxidase) 1-generated ROS (reactive
      oxygen species) play critical regulatory roles in various cellular processes, yet
      little is known of direct targets for the oxidase. In the present study we show
      that one of the proteins selectively oxidized in response to Nox1-generated ROS
      was ERp72 (endoplasmic reticulum protein 72 kDa) with TRX (thioredoxin) homology
      domains. Oxidation of ERp72 by Nox1 resulted in an inhibition of its reductase
      activity. EGF treatment of cells stimulated the Nox1 activity and the activated
      Nox1 subsequently mediated EGF-induced suppression of the ERp72 reductase
      activity. Co-immunoprecipitation, GST (glutathione transferase) pulldown assays
      and mutational analysis, indicated that Nox1 associates with ERp72, which
      involves its N-terminus encompassing a Ca(2+)-binding site and the first TRX-like
      motif. Furthermore, confocal microscopy showed co-localization between Nox1 and
      ERp72 at the plasma membrane. These results suggest that Nox1 functionally
      associates with ERp72, regulating redox-sensitive signalling pathways in a
      cellular context.

PMID- 18620547
TI  - Substrate specificity and structure of human aminoadipate
      aminotransferase/kynurenine aminotransferase II.
AB  - KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for
      catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the
      only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme
      also catalyses the transamination of aminoadipate to alpha-oxoadipate; therefore
      it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin,
      aminoadipate influences various elements of glutamatergic neurotransmission and
      kills primary astrocytes in the brain. A number of studies dealing with the
      biochemical and functional characteristics of this enzyme exist in the
      literature, but a systematic assessment of KAT II addressing its substrate
      profile and kinetic properties has not been performed. The present study examines
      the biochemical and structural characterization of a human KAT II/AADAT.
      Substrate screening of human KAT II revealed that the enzyme has a very broad
      substrate specificity, is capable of catalysing the transamination of 16 out of
      24 tested amino acids and could utilize all 16 tested alpha-oxo acids as amino
      group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic
      efficiency for individual amino-group donors and acceptors, providing information
      as to its preferred substrate affinity. Structural analysis of the human KAT II
      complex with alpha-oxoglutaric acid revealed a conformational change of an N
      terminal fraction, residues 15-33, that is able to adapt to different substrate
      sizes, which provides a structural basis for its broad substrate specificity.

PMID- 18620549
TI  - Heparin-induced thrombocytopenia during renal replacement therapy in the
      intensive care unit.
AB  - Whereas some 30% to 50% of patients admitted to the intensive care unit develop
      thrombocytopenia during their stay, the incidence of heparin-induced
      thrombocytopenia (HIT) remains low, at around 0.3% to 0.5%. Lasocki and
      colleagues prospectively tested patients with premature clotting of the
      hemofiltration circuit for HIT, and reported a 25% incidence of HIT, particularly
      if the circuit clotted within 6 hours. By switching the anticoagulant from
      heparin to danaparoid, the hemofiltration circuit survival and urea clearances
      improved. HIT should therefore be clinically suspected if extracorporeal circuits
      clot repeatedly.

PMID- 18620550
TI  - Normal adrenocortical function on initial testing in the intensive care unit: not
      a long-term warranty.
AB  - There has been a lot of debate about the concept of relative adrenocortical
      insufficiency (often defined as a reduced response to corticotropin) as a
      pathophysiological explanation of steroid effects in septic shock. Less is known
      about the prevalence of absolute adrenocortical insufficiency based on more usual
      definitions (low baseline and corticotropin stimulated cortisol). A study by Wu
      and colleagues provides convincing evidence that critically ill patients could
      evolve from a normal adrenal status towards very low cortisol levels within a few
      days. Although the exact consequences of these findings deserve more
      investigation, adrenal testing should not be omitted in patients not improving
      their hemodynamic status.

PMID- 18620551
TI  - Applying logic to pulmonary artery catheter use.

PMID- 18620552
TI  - Stage debut for the elusive Drosophila insulin-like growth factor binding
      protein.
AB  - Insulin-like growth factor (IGF) binding proteins provide a layer of complexity
      to the insulin/IGF signaling system in mammals, but only now, in a recent study
      in Journal of Biology, has one such protein been functionally characterized in
      Drosophila.

PMID- 18620554
TI  - Protein evolution of ANTP and PRD homeobox genes.
AB  - BACKGROUND: Although homeobox genes have been the subject of many studies, little
      is known about the main amino acid changes that occurred early in the evolution
      of genes belonging to different classes. RESULTS: In this study, we report a
      method for the fast and efficient retrieval of sequences belonging to the ANTP
      (HOXL and NKL) and PRD classes. Furthermore, we look for diagnostic amino acid
      residues that can be used to distinguish HOXL, NKL and PRD genes. CONCLUSION: The
      reported protein features will facilitate the robust classification of homeobox
      genes from newly sequenced bilaterian genomes. Nevertheless, in non-bilaterian
      genomes our findings must be cautiously applied. In principle, as long as a good
      manually curated data set is available the approach here described can be applied
      to non-bilaterian organisms as well. Our results help focus experimental studies
      onto investigating the biochemical functions of key homeodomain residues in
      different gene classes.

PMID- 18620553
TI  - Survey of childhood empyema in Asia: implications for detecting the unmeasured
      burden of culture-negative bacterial disease.
AB  - BACKGROUND: Parapneumonic empyema continues to be a disease of significant
      morbidity and mortality among children despite recent advances in medical
      management. To date, only a limited number of studies have assessed the burden of
      empyema in Asia. METHODS: We surveyed medical records of four representative
      large pediatric hospitals in China, Korea, Taiwan and Vietnam using ICD-10
      diagnostic codes to identify children <16 years of age hospitalized with empyema
      or pleural effusion from 1995 to 2005. We also accessed microbiology records of
      cultured empyema and pleural effusion specimens to describe the trends in the
      epidemiology and microbiology of empyema. RESULTS: During the study period, we
      identified 1,379 children diagnosed with empyema or pleural effusion (China, n =
      461; Korea, n = 134; Taiwan, n = 119; Vietnam, n = 665). Diagnoses of pleural
      effusion (n = 1,074) were 3.5 times more common than of empyema (n = 305),
      although the relative proportions of empyema and pleural effusion noted in
      hospital records varied widely between the four sites, most likely because of
      marked differences in coding practices. Although pleural effusions were reported
      more often than empyema, children with empyema were more likely to have a
      cultured pathogen. In addition, we found that median age and gender distribution
      of children with these conditions were similar across the four countries. Among
      1,379 empyema and pleural effusion specimens, 401 (29%) were culture positive.
      Staphylococcus aureus (n = 126) was the most common organism isolated, followed
      by Streptococcus pneumoniae (n = 83), Pseudomonas aeruginosa (n = 37) and
      Klebsiella (n = 35) and Acinetobacter species (n = 34). CONCLUSION: The age and
      gender distribution of empyema and pleural effusion in children in these
      countries are similar to the US and Western Europe. S. pneumoniae was the second
      leading bacterial cause of empyema and pleural effusion among Asian children. The
      high proportion of culture-negative specimens among patients with pleural
      effusion or empyema suggests that culture may not be a sufficiently sensitive
      diagnostic method to determine etiology in the majority of cases. Future
      prospective studies in different countries would benefit from standardized case
      definitions and coding practices for empyema. In addition, more sensitive
      diagnostic methods would improve detection of pathogens and could result in
      better prevention, treatment and outcomes of this severe disease.

PMID- 18620555
TI  - Zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, demonstrates potent
      antitumor effects but is unable to potentiate antitumor effects of
      chemotherapeutics in mice.
AB  - BACKGROUND: HO-1 participates in the degradation of heme. Its products can exert
      unique cytoprotective effects. Numerous tumors express high levels of HO-1
      indicating that this enzyme might be a potential therapeutic target. In this
      study we decided to evaluate potential cytostatic/cytotoxic effects of zinc
      protoporphyrin IX (Zn(II)PPIX), a selective HO-1 inhibitor and to evaluate its
      antitumor activity in combination with chemotherapeutics. METHODS:
      Cytostatic/cytotoxic effects of Zn(II)PPIX were evaluated with crystal violet
      staining and clonogenic assay. Western blotting was used for the evaluation of
      protein expression. Flow cytometry was used to evaluate the influence of
      Zn(II)PPIX on the induction of apoptosis and generation of reactive oxygen
      species. Knock-down of HO-1 expression was achieved with siRNA. Antitumor effects
      of Zn(II)PPIX alone or in combination with chemotherapeutics were measured in
      transplantation tumor models. RESULTS: Zn(II)PPIX induced significant
      accumulation of reactive oxygen species in tumor cells. This effect was partly
      reversed by administration of exogenous bilirubin. Moreover, Zn(II)PPIX exerted
      potent cytostatic/cytotoxic effects against human and murine tumor cell lines.
      Despite a significant time and dose-dependent decrease in cyclin D expression in
      Zn(II)PPIX-treated cells no accumulation of tumor cells in G1 phase of the cell
      cycle was observed. However, incubation of C-26 cells with Zn(II)PPIX increased
      the percentage of cells in sub-G1 phase of the cells cycle. Flow cytometry
      studies with propidium iodide and annexin V staining as well as detection of
      cleaved caspase 3 by Western blotting revealed that Zn(II)PPIX can induce
      apoptosis of tumor cells. B16F10 melanoma cells overexpressing HO-1 and
      transplanted into syngeneic mice were resistant to either Zn(II)PPIX or antitumor
      effects of cisplatin. Zn(II)PPIX was unable to potentiate antitumor effects of 5
      fluorouracil, cisplatin or doxorubicin in three different tumor models, but
      significantly potentiated toxicity of 5-FU and cisplatin. CONCLUSION: Inhibition
      of HO-1 exerts antitumor effects but should not be used to potentiate antitumor
      effects of cancer chemotherapeutics unless procedures of selective tumor
      targeting of HO-1 inhibitors are developed.

PMID- 18620556
TI  - Hemorrhage associated with hepatic artery pseudoaneurysms after regional
      chemotherapy with floxuridine: case report.
AB  - Pseudoaneurysms of the hepatic artery are a rare complication in patients with
      primary or secondary liver tumors treated with intra-arterial chemotherapy. We
      present two patients who developed this complication after placement of a
      catheter system into the gastroduodenal artery and initiation of regional
      chemotherapy with floxuridine. Diagnosis was made after symptomatic bleeding
      occurred, necessitating emergency angiography with coil embolization.
      Pseudoaneurysms usually occur after mechanical damage of the vessel wall, but the
      chemical toxicity of floxuridine may add to the development of vascular
      impairment.

PMID- 18620557
TI  - The Hypocrea jecorina (Trichoderma reesei) hypercellulolytic mutant RUT C30 lacks
      a 85 kb (29 gene-encoding) region of the wild-type genome.
AB  - BACKGROUND: The hypercellulolytic mutant Hypocrea jecorina (anamorph Trichoderma
      reesei) RUT C30 is the H. jecorina strain most frequently used for cellulase
      fermentations and has also often been employed for basic research on cellulase
      regulation. This strain has been reported to contain a truncated carbon
      catabolite repressor gene cre1 and is consequently carbon catabolite derepressed.
      To date this and an additional frame-shift mutation in the glycoprotein
      processing beta-glucosidase II encoding gene are the only known genetic
      differences in strain RUT C30. RESULTS: In the present paper we show that H.
      jecorina RUT C30 lacks an 85 kb genomic fragment, and consequently misses
      additional 29 genes comprising transcription factors, enzymes of the primary
      metabolism and transport proteins. This loss is already present in the ancestor
      of RUT C30--NG 14--and seems to have occurred in a palindromic AT-rich repeat
      (PATRR) typically inducing chromosomal translocations, and is not linked to the
      cre1 locus. The mutation of the cre1 locus has specifically occurred in RUT C30.
      Some of the genes that are lacking in RUT C30 could be correlated with pronounced
      alterations in its phenotype, such as poor growth on alpha-linked oligo- and
      polyglucosides (loss of maltose permease), or disturbance of osmotic homeostasis.
      CONCLUSION: Our data place a general caveat on the use of H. jecorina RUT C30 for
      further basic research.

PMID- 18620558
TI  - Conditional variable importance for random forests.
AB  - BACKGROUND: Random forests are becoming increasingly popular in many scientific
      fields because they can cope with "small n large p" problems, complex
      interactions and even highly correlated predictor variables. Their variable
      importance measures have recently been suggested as screening tools for, e.g.,
      gene expression studies. However, these variable importance measures show a bias
      towards correlated predictor variables. RESULTS: We identify two mechanisms
      responsible for this finding: (i) A preference for the selection of correlated
      predictors in the tree building process and (ii) an additional advantage for
      correlated predictor variables induced by the unconditional permutation scheme
      that is employed in the computation of the variable importance measure. Based on
      these considerations we develop a new, conditional permutation scheme for the
      computation of the variable importance measure. CONCLUSION: The resulting
      conditional variable importance reflects the true impact of each predictor
      variable more reliably than the original marginal approach.

PMID- 18620559
TI  - Temporal trends in breast cancer presentation in the third world.
AB  - BACKGROUND: Third world breast cancer is characterized by late presentation,
      occurrence at relatively young ages and dismal mortality. This poor outcome has
      encouraged patients to patronize quacks and alternative healers. Public control
      measures have targeted mainly public education and provision of screening
      facilities. Recent reports from the developed world indicate a high association
      with obesity, tobacco and alcohol, habits which though not currently very popular
      in the third world are nevertheless increasingly accepted. METHODS: A prospective
      study initiated in 1985 for all breast cancer patients attending 4 hospitals
      located in the Eastern Nigeria heartland where the author practiced. On
      attendance to hospital detailed epidemiological data including social habits were
      collected from patients. RESULTS: Reports from our first series [1987-97] showed
      some improvement in terms of earlier presentation compared to a historical
      control of earlier reports from the sub-region. Reports from the present study
      showed that this improvement has not been maintained probably as a result of
      diversion of public health campaign finances to HIV/AIDS. However there is an
      increasing mean age of presentation due to a higher representation of above 70
      years age group and a significant reduction in parity. Alcohol intake and smoking
      have remained at low levels among the patients. CONCLUSION: There is need to take
      another look at cancer public health campaign mechanisms in the face of competing
      demands from HIV. Public control measures should include among others teaching of
      Breast Self Examination [BSE] to patients, Clinical Breast Examination [CBE] to
      health workers and opportunistic CBE to all patients. Strenuous efforts should be
      made to break the vicious cycle of late presentation, poor treatment outcome and
      reluctance of patients to present to health facilities because of poor outcome.

PMID- 18620560
TI  - The usefulness of a new rapid diagnostic test, the First Response Malaria Combo
      (pLDH/HRP2) card test, for malaria diagnosis in the forested belt of central
      India.
AB  - BACKGROUND: Malaria presents a diagnostic challenge in tribal belt of central
      India where two Plasmodium species, Plasmodium falciparum and Plasmodium vivax,
      are prevalent. In these areas, rapid detection of the malaria parasites and early
      treatment of infection remain the most important goals of disease management.
      Therefore, the usefulness of a new rapid diagnostic (RDT), the First Response(R)
      Combo Malaria Ag (pLDH/HRP2) card test was assessed for differential diagnosis
      between P. falciparum with other Plasmodium species in remote villages of
      Jabalpur district. METHODS: A finger prick blood sample was collected to prepare
      blood smear and for testing with the RDT after taking informed consent. The
      figures for sensitivity, specificity, accuracy and predictive values were
      calculated using microscopy as gold standard. RESULTS: Analysis revealed that
      overall, the RDT was 93% sensitive, 85% specific with a positive predictive value
      (PPV) of 79%, and a negative predictive value (NPV) of 95%. The accuracy 88% and
      J-index was 0.74. For P. falciparum, the sensitivity and specificity of the test
      were 96% and 95% respectively, with a PPV of 85% and a NPV of 99%. The RDT
      accuracy 95% and J-index was 0.84. For non-falciparum malaria, the sensitivity,
      specificity and accuracy were 83%, 94% and 92% respectively with a PPV of 69% and
      a NPV of 97%. CONCLUSION: The RDTs are easy to use, reliable and simple to
      interpret. RDTs are more suited to health workers in situations where health
      services are deficient or absent. Therefore, the test can be used as an
      epidemiological tool for the rapid screening of malaria.

PMID- 18620561
TI  - Dignity in the care of older people - a review of the theoretical and empirical
      literature.
AB  - BACKGROUND: Dignity has become a central concern in UK health policy in relation
      to older and vulnerable people. The empirical and theoretical literature relating
      to dignity is extensive and as likely to confound and confuse as to clarify the
      meaning of dignity for nurses in practice. The aim of this paper is critically to
      examine the literature and to address the following questions: What does dignity
      mean? What promotes and diminishes dignity? And how might dignity be
      operationalised in the care of older people?This paper critically reviews the
      theoretical and empirical literature relating to dignity and clarifies the
      meaning and implications of dignity in relation to the care of older people. If
      nurses are to provide dignified care clarification is an essential first step.
      METHODS: This is a review article, critically examining papers reporting
      theoretical perspectives and empirical studies relating to dignity. The following
      databases were searched: Assia, BHI, CINAHL, Social Services Abstracts, IBSS, Web
      of Knowledge Social Sciences Citation Index and Arts & Humanities Citation Index
      and location of books a chapters in philosophy literature. An analytical approach
      was adopted to the publications reviewed, focusing on the objectives of the
      review. RESULTS AND DISCUSSION: We review a range of theoretical and empirical
      accounts of dignity and identify key dignity promoting factors evident in the
      literature, including staff attitudes and behaviour; environment; culture of
      care; and the performance of specific care activities. Although there is scope to
      learn more about cultural aspects of dignity we know a good deal about dignity in
      care in general terms. CONCLUSION: We argue that what is required is to provide
      sufficient support and education to help nurses understand dignity and adequate
      resources to operationalise dignity in their everyday practice. Using the themes
      identified from our review we offer proposals for the direction of future
      research.

PMID- 18620562
TI  - Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the
      polyglandular autoimmune syndrome type II.
AB  - BACKGROUND: Polymorphisms within the insulin gene can influence insulin
      expression in the pancreas and especially in the thymus, where self-antigens are
      processed, shaping the T cell repertoire into selftolerance, a process that
      protects from beta-cell autoimmunity. METHODS: We investigated the role of the 
      2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients
      with a monoglandular autoimmune endocrine disease [patients with isolated type 1
      diabetes (T1D, n = 317), Addison's disease (AD, n = 107) or Hashimoto's
      thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II
      (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy
      controls (HC, n = 275). RESULTS: T1D patients carried significantly more often
      the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms
      than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 x 10-8,
      respectively). The distribution of insulin gene polymorphisms did not show
      significant differences between patients with AD, HT, or APS-II and HC.
      CONCLUSION: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" 
      23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to
      isolated AD, HT or as a part of the APS-II.

PMID- 18620563
TI  - Design paper: The CapOpus trial: a randomized, parallel-group, observer-blinded
      clinical trial of specialized addiction treatment versus treatment as usual for
      young patients with cannabis abuse and psychosis.
AB  - BACKGROUND: A number of studies indicate a link between cannabis-use and
      psychosis as well as more severe psychosis in those with existing psychotic
      disorders. There is currently insufficient evidence to decide the optimal way to
      treat cannabis abuse among patients with psychosis. OBJECTIVES: The major
      objective for the CapOpus trial is to evaluate the additional effect on cannabis
      abuse of a specialized addiction treatment program adding group treatment and
      motivational interviewing to treatment as usual. DESIGN: The trial is designed as
      a randomized, parallel-group, observer-blinded clinical trial. Patients are
      primarily recruited through early-psychosis detection teams, community mental
      health centers, and assertive community treatment teams. Patients are randomized
      to one of two treatment arms, both lasting six months: 1) specialized addiction
      treatment plus treatment as usual or 2) treatment as usual. The specialized
      addiction treatment is manualized and consists of both individual and group-based
      motivational interviewing and cognitive behavioral therapy, and incorporates both
      the family and the case manager of the patient.The primary outcome measure will
      be changes in amount of cannabis consumption over time. Other outcome measures
      will be psychosis symptoms, cognitive functioning, quality of life, social
      functioning, and cost-benefit analyses. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00484302.

PMID- 18620564
TI  - The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific
      expression patterns and involvement in cell spreading and stress response.
AB  - BACKGROUND: FUS, EWS and TAF15 are structurally similar multifunctional proteins
      that were first discovered upon characterization of fusion oncogenes in human
      sarcomas and leukemias. The proteins belong to the FET (previously TET) family of
      RNA-binding proteins and are implicated in central cellular processes such as
      regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA
      processing. In the present study, we investigated the expression and cellular
      localization of FET proteins in multiple human tissues and cell types. RESULTS:
      FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in
      human tissues. The three proteins showed almost ubiquitous nuclear expression and
      FUS and TAF15 were in addition present in the cytoplasm of most cell types.
      Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types.
      Furthermore, FET expression was downregulated in differentiating human embryonic
      stem cells, during induced differentiation of neuroblastoma cells and absent in
      terminally differentiated melanocytes and cardiac muscle cells. The FET proteins
      were targeted to stress granules induced by heat shock and oxidative stress and
      FUS required its RNA-binding domain for this translocation. Furthermore, FUS and
      TAF15 were detected in spreading initiation centers of adhering cells.
      CONCLUSION: Our results point to cell-specific expression patterns and functions
      of the FET proteins rather than the housekeeping roles inferred from earlier
      studies. The localization of FET proteins to stress granules suggests activities
      in translational regulation during stress conditions. Roles in central processes
      such as stress response, translational control and adhesion may explain the FET
      proteins frequent involvement in human cancer.

PMID- 18620565
TI  - Distributed usability evaluation of the Pennsylvania Cancer Atlas.
AB  - BACKGROUND: The Pennsylvania Cancer Atlas (PA-CA) is an interactive online atlas
      to help policy-makers, program managers, and epidemiologists with tasks related
      to cancer prevention and control. The PA-CA includes maps, graphs, tables, that
      are dynamically linked to support data exploration and decision-making with
      spatio-temporal cancer data. Our Atlas development process follows a user
      centered design approach. To assess the usability of the initial versions of the
      PA-CA, we developed and applied a novel strategy for soliciting user feedback
      through multiple distributed focus groups and surveys. Our process of acquiring
      user feedback leverages an online web application (e-Delphi). In this paper we
      describe the PA-CA, detail how we have adapted e-Delphi web application to
      support usability and utility evaluation of the PA-CA, and present the results of
      our evaluation. RESULTS: We report results from four sets of users. Each group
      provided structured individual and group assessments of the PA-CA as well as
      input on the kinds of users and applications for which it is best suited. Overall
      reactions to the PA-CA are quite positive. Participants did, however, provide a
      range of useful suggestions. Key suggestions focused on improving interaction
      functions, enhancing methods of temporal analysis, addressing data issues, and
      providing additional data displays and help functions. These suggestions were
      incorporated in each design and implementation iteration for the PA-CA and used
      to inform a set of web-atlas design principles. CONCLUSION: For the Atlas, we
      find that a design that utilizes linked map, graph, and table views is
      understandable to and perceived to be useful by the target audience of cancer
      prevention and control professionals. However, it is clear that considerable
      variation in experience using maps and graphics exists and for those with less
      experience, integrated tutorials and help features are needed. In relation to our
      usability assessment strategy, we find that our distributed, web-based method for
      soliciting user input is generally effective. Advantages include the ability to
      gather information from users distributed in time and space and the relative
      anonymity of the participants while disadvantages include less control over when
      and how often participants provide input and challenges for obtaining rich input.

PMID- 18620566
TI  - Effect of variable heat transfer coefficient on tissue temperature next to a
      large vessel during radiofrequency tumor ablation.
AB  - BACKGROUND: One of the current shortcomings of radiofrequency (RF) tumor ablation
      is its limited performance in regions close to large blood vessels, resulting in
      high recurrence rates at these locations. Computer models have been used to
      determine tissue temperatures during tumor ablation procedures. To simulate large
      vessels, either constant wall temperature or constant convective heat transfer
      coefficient (h) have been assumed at the vessel surface to simulate convection.
      However, the actual distribution of the temperature on the vessel wall is non
      uniform and time-varying, and this feature makes the convective coefficient
      variable. METHODS: This paper presents a realistic time-varying model in which h
      is a function of the temperature distribution at the vessel wall. The finite
      element method (FEM) was employed in order to model RF hepatic ablation. Two
      geometrical configurations were investigated. The RF electrode was placed at
      distances of 1 and 5 mm from a large vessel (10 mm diameter). RESULTS: When the
      ablation procedure takes longer than 1-2 min, the attained coagulation zone
      obtained with both time-varying h and constant h does not differ significantly.
      However, for short duration ablation (5-10 s) and when the electrode is 1 mm away
      from the vessel, the use of constant h can lead to errors as high as 20% in the
      estimation of the coagulation zone. CONCLUSION: For tumor ablation procedures
      typically lasting at least 5 min, this study shows that modeling the heat sink
      effect of large vessels by applying constant h as a boundary condition will yield
      precise results while reducing computational complexity. However, for other
      thermal therapies with shorter treatment using a time-varying h may be necessary.

PMID- 18620568
TI  - Constrictive pericarditis is an easily overlooked cause of right heart failure: a
      case report.
AB  - We describe a patient who suffered progressive right heart failure of unknown
      aetiology, despite a lengthy series of hospital investigations. Constrictive
      pericarditis had not been suspected during life, and was ultimately diagnosed as
      an autopsy finding. The salient clinical features and confirmatory investigations
      for this unusual disorder are reviewed. The case reminds us to consider the
      possibility of constrictive pericarditis in patients with unexplained chronic
      right heart failure, so that prompt investigation and treatment can be
      instigated.

PMID- 18620567
TI  - Palliative care in advanced dementia; A mixed methods approach for the
      development of a complex intervention.
AB  - BACKGROUND: There is increasing interest in improving the quality of care that
      patients with advanced dementia receive when they are dying. Our understanding of
      the palliative care needs of these patients and the natural history of advanced
      disease is limited. Many people with advanced dementia have unplanned emergency
      admissions to the acute hospital; this is a critical event: half will die within
      6 months. These patients have complex needs but often lack capacity to express
      their wishes. Often carers are expected to make decisions. Advance care planning
      discussions are rarely performed, despite potential benefits such more consistent
      supportive healthcare, a reduction in emergency admissions to the acute hospital
      and better resolution of carer bereavement. DESIGN/METHODS: We have used the MRC
      complex interventions framework, a "bottom-up" methodology, to develop an
      intervention for patients with advanced dementia and their carers aiming to 1)
      define end of life care needs for both patients and carers, 2) pilot a palliative
      care intervention and 3) produce a framework for advance care planning for
      patients.The results of qualitative phase 1 work, which involved interviews with
      carers, hospital and primary care staff from a range of disciplines, have been
      used to identify key barriers and challenges. For the exploratory trial, 40
      patients will be recruited to each of the control and intervention groups. The
      intervention will be delivered by a nurse specialist. We shall investigate and
      develop methodology for a phase 3 randomised controlled trial. For example we
      shall explore the feasibility of randomisation, how best to optimise recruitment,
      decide on appropriate outcomes and obtain data for power calculations. We will
      evaluate whether the intervention is pragmatic, feasible and deliverable on acute
      hospital wards and test model fidelity and its acceptability to carers, patients
      and staff. DISCUSSION: Results of qualitative phase 1 work suggested that carers
      and staff were keen to discuss these issues and guided the development of the
      intervention and choice of outcomes. This will be vital in moving to a phase III
      trial that is pragmatic and feasible for these complex patients within the NHS.
      TRIAL REGISTRATION: ISRCTN03330837.

PMID- 18620569
TI  - Primary malignant melanoma of the lower oesophagus presenting with dysphagia and
      upper gastrointestinal bleeding.
AB  - Primary malignant melanoma of the oesophagus is an exceedingly rare oesophageal
      neoplasm. It accounts for less than 0.1% of all primary oesophageal tumours. Less
      than 262 cases have been documented till today. Surgical resection with re
      establishment of gastrointestinal continuity is the treatment of choice. However,
      haematogenic and lymphogenic metastases are common and despite advances in
      surgery, radiotherapy and chemotherapy, this tumour continues to be a highly
      aggressive neoplasm with poor prognosis. The case of a 64 year-old lady with this
      tumour is presented.

PMID- 18620570
TI  - The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin
      deficiency.
AB  - BACKGROUND: Genetic variation may underlie phenotypic variation in chronic
      obstructive pulmonary disease (COPD) in subjects with and without alpha 1
      antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and
      may underlie the poor replication of previous genetic studies. This study
      investigated subjects with AATD to determine the relationship between specific
      phenotypes and TNFalpha polymorphisms. METHODS: 424 unrelated subjects of the
      PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung
      function and radiological presence of emphysema and bronchiectasis. A subset of
      subjects with 3 years consecutive lung function data was assessed for decline of
      lung function. Four single nucleotide polymorphisms (SNPs) tagging TNFalpha were
      genotyped using TaqMan(R) genotyping technologies and compared between subjects
      affected by each phenotype and those unaffected. Plasma TNFalpha levels were
      measured in all PiZZ subjects. RESULTS: All SNPs were in Hardy-Weinberg
      equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele
      (p = 0.01) frequency was seen between subjects with and without chronic
      bronchitis, independent of the presence of other phenotypes. TNFalpha plasma
      level showed no phenotypic or genotypic associations. CONCLUSION: Variation in
      TNFalpha is associated with chronic bronchitis in AATD.

PMID- 18620571
TI  - Cross-platform comparison of SYBR Green real-time PCR with TaqMan PCR,
      microarrays and other gene expression measurement technologies evaluated in the
      MicroArray Quality Control (MAQC) study.
AB  - BACKGROUND: The MicroArray Quality Control (MAQC) project evaluated the inter-
      and intra-platform reproducibility of seven microarray platforms and three
      quantitative gene expression assays in profiling the expression of two
      commercially available Reference RNA samples (Nat Biotechnol 24:1115-22, 2006).
      The tested microarrays were the platforms from Affymetrix, Agilent Technologies,
      Applied Biosystems, GE Healthcare, Illumina, Eppendorf and the National Cancer
      Institute, and quantitative gene expression assays included TaqMan Gene
      Expression PCR Assay, Standardized (Sta) RT-PCRtrade mark and QuantiGene. The
      data showed great consistency in gene expression measurements across different
      microarray platforms, different technologies and test sites. However, SYBR Green
      real-time PCR, another common technique utilized by half of all real-time PCR
      users for gene expression measurement, was not addressed in the MAQC study. In
      the present study, we compared the performance of SYBR Green PCR with TaqMan PCR,
      microarrays and other quantitative technologies using the same two Reference RNA
      samples as the MAQC project. We assessed SYBR Green real-time PCR using
      commercially available RT2 Profilertrade mark PCR Arrays from SuperArray,
      containing primer pairs that have been experimentally validated to ensure gene
      specificity and high amplification efficiency. RESULTS: The SYBR Green PCR Arrays
      exhibit good reproducibility among different users, PCR instruments and test
      sites. In addition, the SYBR Green PCR Arrays have the highest concordance with
      TaqMan PCR, and a high level of concordance with other quantitative methods and
      microarrays that were evaluated in this study in terms of fold-change correlation
      and overlap of lists of differentially expressed genes. CONCLUSION: These data
      demonstrate that SYBR Green real-time PCR delivers highly comparable results in
      gene expression measurement with TaqMan PCR and other high-density microarrays.

PMID- 18620572
TI  - In-vitro antimycobacterial drug susceptibility testing of non-tubercular
      mycobacteria by tetrazolium microplate assay.
AB  - BACKGROUND: Non-tubercular mycobacteria (NTM) has not been given due attention
      till the recent epidemic of HIV. This has led to increasing interest of health
      care workers in their biology, epidemiology and drug resistance. However, timely
      detection and drug susceptibility profiling of NTM isolates are always difficult
      in resource poor settings like India. Furthermore, no standardized methodology or
      guidelines are available to reproduce the results with clinical concordance.
      OBJECTIVE: To find an alternative and rapid method for performing the drug
      susceptibility assay in a resource limited settings like India, we intended to
      evaluate the utility of Tetrazolium microplate assay (TEMA) in comparison with
      proportion method for reporting the drug resistance in clinical isolates of NTM.
      METHODS: A total of fifty-five NTM isolates were tested for susceptibility
      against Streptomycin, Rifampicin, Ethambutol, Ciprofloxacin, Ofloxacin,
      Azithromycin, and Clarithromycin by TEMA and the results were compared with agar
      proportion method (APM). RESULTS: Of the 55 isolates, 23 (41.8%) were sensitive
      to all the drugs and the remaining 32 (58.2%) were resistant to at least one
      drug. TEMA had very good concordance with APM except with minor discrepancies.
      Susceptibility results were obtained in the median of 5 to 9 days by TEMA. The
      NTM isolates were highly sensitive against Ofloxacin (98.18% sensitive) and
      Ciprofloxacin (90.09% sensitive). M. mucogenicum was sensitive only to
      Clarithromycin and resistant to all the other drugs tested. The concordance
      between TEMA and APM ranged between 96.4 - 100%. CONCLUSION: Tetrazolium
      Microplate Assay is a rapid and highly reproducible method. However, it must be
      performed only in tertiary level Mycobacteriology laboratories with proper bio
      safety conditions.

PMID- 18620573
TI  - Sinusoidal obstruction syndrome (veno-occlusive disease) in a patient receiving
      bevacizumab for metastatic colorectal cancer: a case report.
AB  - INTRODUCTION: We present the case of a patient with colon cancer who, while
      receiving bevacizumab, developed sinusoidal obstruction syndrome (veno-occlusive
      disease) (SOSVOD). Certain antitumour agents such as 6-mercaptopurine and 6
      thioguanine have also been reported to initiate hepatic SOSVOD in isolated cases.
      There have been no reports so far correlating bevacizumab with SOSVOD. CASE
      PRESENTATION: A 77-year-old man was being treated with oxaliplatin and a modified
      de Gramont regimen of 5-fluorouracil for metastatic colon cancer. Bevacizumab
      (7.5 mg/kg) was added from the seventh cycle onwards. Protracted neutropenia and
      thrombocytopenia led to discontinuation of oxaliplatin after the ninth cycle. A
      computed tomography scan showed complete response and bevacizumab was continued
      for another 3 months, after which time the patient developed right hypochondrial
      pain, transudative ascites, splenomegaly and abnormal liver function tests. Upper
      gastrointestinal endoscopy showed oesophageal varices. Liver biopsy showed
      features considered to be consistent with SOSVOD. Bevacizumab was stopped and a
      policy of watchful waiting was adopted. He tolerated the acute damage to his
      liver and subsequently the ascites resolved and liver function tests normalised.
      CONCLUSION: We need to be aware that bevacizumab can cause sinusoidal obstruction
      syndrome (veno-occlusive disease) and that the occurrence of ascites should not
      be attributed to progressive disease without appropriate evaluation.

PMID- 18620574
TI  - Plasmatic level of neurosin predicts outcome of mild cognitive impairment.
AB  - BACKGROUND: Mild Cognitive Impairment (MCI) is a disorder considered to be a
      transitional stage from health to dementia. Diagnosis of dementias at these early
      stages is always troublesome because the pathophysiologic events leading to
      dementia precede clinical symptoms. Thus, the development of biomarkers that can
      be used to support the diagnosis of dementias at early stages is rapidly becoming
      a high priority. We have recently reported the value of measuring plasmatic
      levels of neurosin in the diagnosis of Alzheimer's disease (AD). The aim of this
      study is to determine whether measuring plasmatic concentration of neurosin is a
      valuable test to predict progression of MCI. METHODS: Plasmatic neurosin
      concentrations were measured in 68 MCI patients and 70 controls subjects. Blood
      samples were obtained at the beginning of the study. Sixty six patients diagnosed
      with MCI were observed for 18 months. In 36 patients a second blood sample was
      obtained at the endpoint. RESULTS: The mean value of plasmatic neurosin
      concentration differs significantly between MCI patients who converted to
      Dementia with vascular component, those who converted to AD, or those who
      remained at MCI stage. The relative risk of developing Dementia with vascular
      component when neurosin levels are higher than 5.25 ng/ml is 13 while the
      relative risk of developing mild AD when neurosin levels are lower than 5.25
      ng/ml is 2. Increases in the levels of neurosin indicate progression to Dementia
      with vascular component. CONCLUSION: The measurement of plasmatic neurosin level
      in patients diagnosed with MCI may predict conversion from MCI to Dementia with
      vascular component. A single measurement is also valuable to estimate the risk of
      developing AD and Dementia with vascular component. Finally, repeated measurement
      of plasmatic neurosin might be a useful test to predict outcome in patients with
      MCI.

PMID- 18620575
TI  - Factors influencing the growth hormone peak and plasma insulin-like growth factor
      I in young adults with pituitary stalk interruption syndrome.
AB  - BACKGROUND: The diagnostic criteria for growth hormone (GH) deficiency (GHD) in
      adolescents and young adults are not yet clearly established.We evaluated the
      factors influencing the GH peak and plasma insulin-like growth factor (IGF) I in
      order to determine the cut-off limits for the diagnosis of GHD during the
      transition period. METHODS: 21 patients treated for GHD due to pituitary stalk
      interruption syndrome at 5.7 +/- 4.1 years were reevaluated at 16.0 +/- 1.8
      years, 0.6 +/- 0.6 years after the end of GH treatment. Group 1 had isolated GHD
      (n = 9) and group 2 had multiple pituitary deficiencies (n = 12), including
      deficiencies of thyroid stimulating (n = 12), adrenocorticotropin (n = 8) and
      gonadotropin (n = 9) hormones. RESULTS: At diagnosis, group 1 had a greater
      pituitary height (2.8 +/- 1.2 vs 1.6 +/- 1.1 mm, P = 0.03) and GH peak (3.8 +/-
      1.9 vs 1.6 +/- 1.5 ng/ml, P < 0.02) than did group 2.At last evaluation, group 1
      had greater GH peak (3.9 +/- 1.9 vs 0.2 +/- 0.4 ng/ml, P = 0.0001) and plasma IGF
      I (211 +/- 88 vs 78 +/- 69 ng/ml, P < 0.002) than did group 2. No group 1 and 9
      group 2 patients had an undetectable GH peak, while the 3 others had GH peak
      below 1 ng/ml.The GH peak decreased between diagnosis and last evaluation only in
      group 2 (P < 0.008). CONCLUSION: The GH peak response to pharmacological
      stimulation and the plasma IGF I concentration in young adults with GHD of
      childhood onset depend on the presence of additional pituitary deficiencies,
      reflecting a more severe defect of the hypothalamic-pituitary axis. The sex
      steroids cannot increase the IGF I if the GH secretion is zero.

PMID- 18620576
TI  - Dominant negative mutant cyclin T1 proteins inhibit HIV transcription by
      specifically degrading Tat.
AB  - BACKGROUND: The positive transcription elongation factor b (P-TEFb) is an
      essential cellular co-factor for the transcription of the human immunodeficiency
      virus type 1 (HIV-1). The cyclin T1 (CycT1) subunit of P-TEFb associates with a
      viral protein, Tat, at the transactivation response element (TAR). This
      represents a critical and necessary step for the stimulation of transcriptional
      elongation. Therefore, CycT1 may serve as a potential target for the development
      of anti-HIV therapies. RESULTS: To create effective inhibitors of HIV
      transcription, mutant CycT1 proteins were constructed based upon sequence
      similarities between CycT1 and other cyclin molecules, as well as the defined
      crystal structure of CycT1. One of these mutants, termed CycT1-U7, showed a
      potent dominant negative effect on Tat-dependent HIV transcription despite a
      remarkably low steady-state expression level. Surprisingly, the expression levels
      of Tat proteins co-expressed with CycT1-U7 were significantly lower than Tat co
      expressed with wild type CycT1. However, the expression levels of CycT1-U7 and
      Tat were restored by treatment with proteasome inhibitors. Concomitantly, the
      dominant negative effect of CycT1-U7 was abolished by these inhibitors.
      CONCLUSION: These results suggest that CycT1-U7 inhibits HIV transcription by
      promoting a rapid degradation of Tat. These mutant CycT1 proteins represent a
      novel class of specific inhibitors for HIV transcription that could potentially
      be used in the design of anti-viral therapy.

PMID- 18620577
TI  - Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in
      Ghanaian children: a randomized efficacy and safety trial with one year follow
      up.
AB  - BACKGROUND: Artesunate-amodiaquine (AS+AQ) and artemether-lumefantrine (AM-L) are
      efficacious artemisinin combination therapy (ACT) regimens that have been widely
      adopted in sub-Saharan Africa. However, there is little information on the
      efficacy of these regimens on subsequent episodes beyond 28 days, or on the
      safety of repeated treatments. METHODS: Children aged six months to 14 years with
      uncomplicated malaria were randomly assigned to treatment with AS+AQ (n = 116),
      or AM-L (n = 111). Recruited subjects were followed-up, initially for 28 days,
      and then monthly for up to one year. All subsequent attacks of uncomplicated
      malaria after 28 days were treated with the same regimen as at randomization.
      Investigations aimed at determining efficacy and side effects were conducted.
      RESULTS: Adequate clinical and parasitological response in subjects with
      evaluable end-points were, 97.1% (100/103) and 98.2% (107/109) on day 14, and
      94.2% (97/103) and 95.3% (102/107) on day 28 in the AM-L and AS+AQ groups,
      respectively. Similar results were obtained after PCR correction. The incidence
      of malaria attacks in the year following recruitment was similar between the two
      treatment groups (p = 0.93). There was a high incidence of potentially AQ
      resistant parasites in the study area. The incidence of adverse events, such as
      pruritus, fatigue and neutropaenia were similar in the two treatment groups. No
      patient showed signs of hearing impairment, and no abnormal neurological signs
      were observed during one year of follow-up. Other adverse events were mild in
      intensity and overlapped with known malaria symptomatology. No adverse event
      exacerbation was observed in any of the subjects who received multiple treatment
      courses with these ACT regimens during one year follow-up. CONCLUSION: AS+AQ and
      AM-L were efficacious for treatment of children with uncomplicated malaria in
      Ghana and drug-related adverse events were rare in treated subjects during one
      year of follow-up. The high prevalence of potentially AQ resistant parasites
      raises questions about the utility of AQ as a partner drug for ACT in Ghana. The
      efficacy of AS+AQ in Ghana requires, therefore, continuous monitoring and
      evaluation. TRIAL REGISTRATION: NCT 00406146 http://www.clinicaltrials.gov.

PMID- 18620578
TI  - Persisting with prevention: the importance of adherence for HIV prevention.
AB  - BACKGROUND: Only four out of 31 completed randomized controlled trials (RCTs) of
      HIV prevention strategies against sexual transmission have shown significant
      efficacy. Poor adherence may have contributed to the lack of effect in some of
      these trials. In this paper we explore the impact of various levels of adherence
      on measured efficacy within an RCT. ANALYSIS: We used simple quantitative methods
      to illustrate the impact of various levels of adherence on measured efficacy by
      assuming a uniform population in terms of sexual behavior and the binomial model
      for the transmission probability per partnership.At 100% adherence the measured
      efficacy within an RCT is a reasonable approximation of the true biological
      efficacy. However, as adherence levels fall, the efficacy measured within a trial
      substantially under-estimates the true biological efficacy. For example, at 60%
      adherence, the measured efficacy can be less than half of the true biological
      efficacy. CONCLUSION: Poor adherence during a trial can substantially reduce the
      power to detect an effect, and improved methods of achieving and maintaining high
      adherence within trials are needed. There are currently 12 ongoing HIV prevention
      trials, all but one of which require ongoing user-adherence. Attention must be
      given to methods of maximizing adherence when piloting and designing RCTs and HIV
      prevention programmes.

PMID- 18620579
TI  - Calcitonin gene-related peptide alters the firing rates of hypothalamic
      temperature sensitive and insensitive neurons.
AB  - BACKGROUND: Transient hyperthermic shifts in body temperature have been linked to
      the endogenous hormone calcitonin gene-related peptide (CGRP), which can increase
      sympathetic activation and metabolic heat production. Recent studies have
      demonstrated that these centrally mediated responses may result from CGRP
      dependent changes in the activity of thermoregulatory neurons in the preoptic and
      anterior regions of the hypothalamus (POAH). RESULTS: Using a tissue slice
      preparation, we recorded the single-unit activity of POAH neurons from the adult
      male rat, in response to temperature and CGRP (10 muM). Based on the slope of
      firing rate as a function of temperature, neurons were classified as either warm
      sensitive or temperature insensitive. All warm sensitive neurons responded to
      CGRP with a significant decrease in firing rate. While CGRP did not alter the
      firing rates of some temperature insensitive neurons, responsive neurons showed
      an increase in firing rate. CONCLUSION: With respect to current models of
      thermoregulatory control, these CGRP dependent changes in firing rate would
      result in hyperthermia. This suggests that both warm sensitive and temperature
      insensitive neurons in the POAH may play a role in producing this hyperthermic
      shift in temperature.

PMID- 18620580
TI  - Effects of ginsenosides Re and Rg3 on intracellular redox state and cell
      proliferation in C6 glioma cells.
AB  - BACKGROUND: Cellular redox state is important to cell growth and death. The
      growth of tumor cells may be modulated by intracellular reduced
      glutathione/oxidized glutathione (GSH/GSSG). The present study aims to
      investigate the effects of ginsenosides Re and Rg3 on cellular redox state and
      cell proliferation in C6 glioma cells. METHODS: Cultured C6 glioma cells were
      exposed to various concentrations of either Rg3 or Re for 24 hours. Cell growth
      and death were measured by the BrdU incorporation assay and the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay respectively.
      Cellular redox state was determined by free radical production using flow
      cytometry and GSH/GSSG using spectrofluorometry. RESULTS: At a sub-lethal
      concentration, Re suppressed cell proliferation with a significant decrease in
      BrdU incorporation. Re did not increase reactive oxygen species (ROS) production
      but increased GSH/GSSG via increased activity of gamma glutamylcystenyl synthase
      (gamma-GCS). In contrast, Rg3 increased free radical production and reduced
      GSH/GSSG. The effects of Rg3 were probably due to increased activity of
      glutathione peroxidase (GPx). CONCLUSION: Re and Rg3 alter cellular redox state
      of C6 glioma cells in opposite directions. Changes in cellular redox state
      induced by Re and Rg3 are correlated with the proliferation rates of C6 glioma
      cells.

PMID- 18620581
TI  - Gene silencing by RNAi in mouse Sertoli cells.
AB  - BACKGROUND: RNA interference (RNAi) is a valuable tool in the investigation of
      gene function. The purpose of this study was to examine the availability, target
      cell types and efficiency of RNAi in the mouse seminiferous epithelium. METHODS:
      The experimental model was based on transgenic mice expressing EGFP (enhanced
      green fluorescent protein). RNAi was induced by in vivo transfection of plasmid
      vectors encoding for short hairpin RNAs (shRNAs) targeting EGFP. shRNAs were
      transfected in vivo by microinjection into the seminiferous tubules via the rete
      testis followed by square wave electroporation. As a transfection reporter,
      expression of red fluorescent protein (HcRed 1) was used. Cell types, the
      efficiency of both transfections and RNAi were all evaluated. RESULTS: Sertoli
      cells were the main transfected cells. A reduction of about 40% in the level of
      EGFP protein was detected in cells successfully transfected both in vivo and in
      vitro. However, the efficiency of in vivo transfection was low. CONCLUSION: In
      adult seminiferous epithelial cells, in vivo post-transcriptional gene silencing
      mediated by RNAi via shRNA is efficient in Sertoli cells. Similar levels of RNAi
      were detected both in vivo and in vitro. This also indicates that Sertoli cells
      have the necessary silencing machinery to repress the expression of endogenous
      genes via RNAi.

PMID- 18620582
TI  - Patterns of health-related quality of life and patterns associated with health
      risks among Rhode Island adults.
AB  - BACKGROUND: Health-related quality of life (HRQOL) has become an important
      consideration in assessing the impact of chronic disease on individuals as well
      as in populations. HRQOL is often assessed using multiple indicators. The authors
      sought to determine if multiple indicators of HRQOL could be used to characterize
      patterns of HRQOL in a population, and if so, to examine the association between
      such patterns and demographic, health risk and health condition covariates.
      METHODS: Data from Rhode Island's 2004 Behavioral Risk Factor Surveillance System
      (BRFSS) were used for this analysis. The BRFSS is a population-based random-digit
      dialed telephone survey of adults ages 18 and older. In 2004 RI's BRFSS
      interviewed 3,999 respondents. A latent class regression (LCR) model, using 9
      BRFSS HRQOL indicators, was used to determine latent classes of HRQOL for RI
      adults and to model the relationship between latent class membership and
      covariates. RESULTS: RI adults were categorized into four latent classes of
      HRQOL. Class 1 (76%) was characterized by good physical and mental HRQOL; Class 2
      (9%) was characterized as having physically related poor HRQOL; Class 3 (11%) was
      characterized as having mentally related poor HRQOL; and Class 4 (4%) as having
      both physically and mentally related poor HRQOL. Class 2 was associated with
      older age, being female, unable to work, disabled, or unemployed, no
      participation in leisure time physical activity, or with having asthma or
      diabetes. Class 3 was associated with being female, current smoking, or having
      asthma or disability. Class 4 was associated with almost all the same predictors
      of Classes 2 and 3, i.e. older age, being female, unable to work, disabled, or
      unemployed, no participation in leisure time physical activity, current smoking,
      with having asthma or diabetes, or with low income. CONCLUSION: Using a LCR
      model, the authors found 4 distinct patterns of HRQOL among RI adults. The
      largest class was associated with good HRQOL; three smaller classes were
      associated with poor HRQOL. We identified the characteristics of subgroups at
      higher-risk for each of the three classes of poor HRQOL. Focusing interventions
      on the high-risk populations may be one approach to improving HRQOL in RI.

PMID- 18620583
TI  - A rare myoepithelioma of the sinonasal cavity: case report.
AB  - Myoepithelioma is a rare benign neoplasm. Pure accounting for less than 1% of
      all salivary gland tumors. Only three cases of sinonasal myoepithelioma have been
      reported in the literature. Diagnosis of myoepithelioma through light microscopy
      is possible and immunohistochemistry is done to facilitate the diagnosis. The
      lesion is so rare that there are no specific indications/guidelines for its
      treatment. We report to you a rare case of sinonasal myoepithelioma in a 57 year
      old Asian female.Myoepitheliomas are rare tumours that account for only about 1%
      of all salivary gland tumors. Most are benign, but some can be malignant. Only
      three cases of sinonasal myoepithelioma have been reported in the literature so
      far.

PMID- 18620584
TI  - Finger joint motion generated by individual extrinsic muscles: a cadaveric study.
AB  - BACKGROUND: Our understanding of finger functionality associated with the
      specific muscle is mostly based on the functional anatomy, and the exact motion
      effect associated with an individual muscle is still unknown. The purpose of this
      study was to examine phalangeal joints motion of the index finger generated by
      each extrinsic muscle. METHODS: Ten (6 female and 4 male) fresh-frozen cadaveric
      hands (age 55.2 +/- 5.6 years) were minimally dissected to establish baseball
      sutures at the musculotendinous junctions of the index finger extrinsic muscles.
      Each tendon was loaded to 10% of its force potential and the motion generated at
      the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal
      interphalangeal (DIP) joints was simultaneously recorded using a marker-based
      motion capture system. RESULTS: The flexor digitorum profundus (FDP) generated
      average flexion of 19.7, 41.8, and 29.4 degrees at the MCP, PIP, and DIP joints,
      respectively. The flexor digitorum superficialis (FDS) generated average flexion
      of 24.8 and 47.9 degrees at the MCP and PIP joints, respectively, and no motion
      at the DIP joints. The extensor digitorum communis (EDC) and extensor indicis
      proprius (EIP) generated average extension of 18.3, 15.2, 4.0 degrees and 15.4,
      13.2, 3.7 degrees at the MCP, PIP and DIP joints, respectively. The FDP generated
      simultaneous motion at the PIP and DIP joints. However, the motion generated by
      the FDP and FDS, at the MCP joint lagged the motion generated at the PIP joint.
      The EDC and EIP generated simultaneous motion at the MCP and PIP joints.
      CONCLUSION: The results of this study provide novel insights into the kinematic
      role of individual extrinsic muscles.

PMID- 18620585
TI  - Secondary amenorrhoea due to pheochromocytoma: a case report.
AB  - INTRODUCTION: Pheochromocytoma is a chromaffin cell catecholamine-secreting
      tumour originating from the adrenal medulla. CASE PRESENTATION: We report here an
      unusual presentation of pheochromocytoma with secondary amenorrhoea and its
      resolution after medical treatment with the alpha adrenergic blocker,
      Phenoxybenzamine. CONCLUSION: Pheochromocytoma is a rare cause of secondary
      amenorrhoea.

PMID- 18620586
TI  - Development of methods for the genetic manipulation of Flavobacterium columnare.
AB  - BACKGROUND: Flavobacterium columnare is the causative agent of columnaris
      disease, a disease affecting many freshwater fish species. Methods for the
      genetic manipulation for some of the species within the Bacteroidetes, including
      members of the genus Flavobacterium, have been described, but these methods were
      not adapted to work with F. columnare. RESULTS: As a first step toward developing
      a robust set of genetic tools for F. columnare, a protocol was developed to
      introduce the E. coli - Flavobacterium shuttle vector pCP29 into F. columnare
      strain C#2 by conjugal mating at an efficiency of 1.5 x 10(-3) antibiotic
      resistant transconjugants per recipient cell. Eight of eleven F. columnare
      strains tested were able to receive pCP29 using the protocol. pCP29 contains the
      cfxA and ermF genes, conferring both cefoxitin and erythromycin resistance to
      recipient cells. Selection for pCP29 introduction into F. columnare was dependent
      on cfxA, as ermF was found not to provide strong resistance to erythromycin. This
      is in contrast to other Flavobacterium species where ermF-based erythromycin
      resistance is strong. The green fluorescent protein gene (gfp) was introduced
      into F. columnare strains under the control of two different native
      Flavobacterium promoters, demonstrating the potential of this reporter system for
      the study of gene expression. The transposon Tn4351 was successfully introduced
      into F. columnare, but the method was dependent on selecting for erythromycin
      resistance. To work, low concentrations of antibiotic (1 microg ml(-1)) were
      used, and high levels of background growth occurred. These results demonstrate
      that Tn4351 functions in F. columnare but that it is not an effective mutagenesis
      tool due to its dependence on erythromycin selection. Attempts to generate
      mutants via homologous recombination met with limited success, suggesting that
      RecA dependent homologous recombination is rare in F. columnare. CONCLUSION: The
      conjugation protocol developed as part of this study represents a significant
      first step towards the development of a robust set of genetic tools for the
      manipulation of F. columnare. The availability of this protocol will facilitate
      studies aimed at developing a deeper understanding of the virulence mechanisms of
      this important pathogen.

PMID- 18620587
TI  - Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age
      related hearing loss in the Fischer 344/NHsd rat.
AB  - BACKGROUND: The Fischer 344/NHsd rat undergoes age-related, progressive, high
      frequency hearing loss beginning at age 12 months. The loss has been linked to
      defects/death in the outer hair cells related to oxidative stress originating in
      the mitochondria. Acetyl L-carnitine (ALCAR) is known to enhance mitochondrial
      bioenergetics and membrane efficiency. Therefore, ALCAR was targeted as a
      possible pharmacologic intervention to prevent, or even restore, hearing loss
      from aging. METHODS: Three different paradigms were used to deliver ALCAR to
      aging Fischer 344/NHsd rats. Rats in each condition had their hearing evaluated
      by auditory brainstem responses before, during, and after treatment. First, 24
      month-old rats were given ALCAR (100 mg/kg dissolved 25 mg/ml in saline) by IP
      injection daily for one month. Second, 18-month-old rats were given ALCAR (100
      mg/kg) by oral gavage for 90 days. Third, 15-month-old rats were given ALCAR (100
      mg/kg) by oral gavage for 90 days. Control rats in each condition received saline
      by i.p. injection or gavage. RESULTS: Hearing thresholds of the three sets of
      ALCAR-treated animals were never significantly different from their matched
      controls before, during, or after the treatments at any of the five test stimuli
      (5, 10, 20, and 40 kHz tone bursts and a click). CONCLUSION: The current study
      does not provide evidence that age-related hearing loss in the Fischer 344/NHsd
      rat can be altered with systemic administration of ALCAR.

PMID- 18620589
TI  - Regulation of thymus-dependent and thymus-independent production of
      immunoglobulin G subclasses by Galpha12 and Galpha13.
AB  - BACKGROUND: A previous study from this laboratory showed that Galpha12 members
      participate in the production of inflammatory cytokines. In spite of the
      identification of B cell homeostasis responses regulated by Galpha13, the
      functional roles of Galpha12 members in the production of immunoglobulin (Ig)
      isotypes remained unknown. This study investigated whether Galpha12 members are
      involved in the Ig isotype antibody production with the purpose of establishing
      their functions in thymus-dependent and thymus-independent humoral responses.
      RESULTS: Mice lacking Galpha12 and/or Galpha13 showed an impaired antigen
      specific antibody production promoted by challenge(s) of ovalbumin or
      trinitrophenyl-lipopolysaccharide (TNP-LPS), used for thymus-dependent and thymus
      independent stimuli, respectively. Homozygous knockout (KO) of Galpha12 or double
      heterozygous KO of Galpha12/Galpha13 significantly reduced the antigen-specific
      total IgG level after multiple ovalbumin immunizations with decreases in the
      production of IgG1, IgG2a and IgG2b subclasses, as compared to wild type control.
      In contrast, IgM production was not decreased. Moreover, mice deficient in
      Galpha12 or partially deficient in Galpha13 or Galpha12/Galpha13 showed
      significantly low production of IgG2b in response to TNP-LPS. In TNP-LPS-injected
      mice, IgG1 and IgG2a productions were unaffected by the G protein KOs.
      CONCLUSION: Our results demonstrate that both Galpha12 and Galpha13 are
      essentially involved in thymus-dependent and independent production of IgG
      subclasses, implying that the G-proteins contribute to the process of antigen
      specific IgG antibody production.

PMID- 18620590
TI  - How do surgical pathologists evaluate critical diagnoses (critical values)?
AB  - BACKGROUND: After introduction of the concept of critical value (CV) in
      laboratory medicine, some efforts were performed to define possible critical
      values in surgical pathology. Critical diagnosis (critical value) is a concept
      recently established in surgical pathology and is a challenging issue among
      pathologists and clinical specialists. The concept may be the subject of
      variation according to the geographical or work setting differences. The current
      study was performed to bring the contribution of the Iranian pathologists to the
      evolving concept of critical diagnoses (critical values) in surgical pathology.
      MATERIALS AND METHODS: During annual meeting of Iranian Pathologist Society,
      November 2006, Tehran, Iran, anonymous questionnaires were distributed among
      participants. They were requested to openly name conditions in which a
      pathologist should communicate the results immediately with clinicians. RESULTS:
      147 pathologists completed the questionnaire. They were varied in their level of
      experience and setting of workplace. Each participant referred to 1-7 (mean 3)
      conditions as CV. About 90 different conditions which were considered as CV by
      participants were extracted from the questionnaires. DISCUSSION: The list of
      conditions obtained through this survey as CVs in surgical pathology covered most
      items previously described in literature. Major differences are low number (or
      lack) of refers to some relatively routine and potentially important conditions
      and considering many unimportant conditions as CV by participants of present
      survey. Almost all conducted surveys have been performed on this issue so far
      (including the present survey) suffer from lack of supportive scientific
      evidences and based mainly on experience and common sense of participants in
      survey. Potential problems with application of CV concept in daily routine work
      flow of pathology, particularly in developing countries like Iran, were
      discussed.

PMID- 18620588
TI  - Pharmacological switch in Abeta-fiber stimulation-induced spinal transmission in
      mice with partial sciatic nerve injury.
AB  - BACKGROUND: We have previously demonstrated that different spinal transmissions
      are involved in the nociceptive behavior caused by electrical stimulation of
      Abeta-, Adelta- or C-fibers using a Neurometer in naive mice. In this study, we
      attempted to pharmacologically characterize the alteration in spinal transmission
      induced by partial sciatic nerve injury in terms of nociceptive behavior and
      phosphorylation of extracellular signal-regulated kinase (pERK) in the spinal
      dorsal horn. RESULTS: Abeta-fiber responses (2000-Hz), which were selectively
      blocked by the AMPA/kainate antagonist CNQX in naive mice, were hypersensitized
      but blocked by the NMDA receptor antagonists MK-801 and AP-5 in injured mice in
      an electrical stimulation-induced paw withdrawal (EPW) test. Although Adelta
      fiber responses (250-Hz) were also hypersensitized by nerve injury, there was no
      change in the pharmacological characteristics of Adelta-fiber responses through
      NMDA receptors. On the contrary, C-fiber responses (5-Hz) were hyposensitized by
      nerve injury. Moreover, Adelta- and C-, but not Abeta-fiber stimulations
      significantly increased the number of pERK-positive neurons in the superficial
      spinal dorsal horns of naive mice, and corresponding antagonists used in the EPW
      test inhibited this increase. In mice with nerve injury, Abeta- as well as Adelta
      fiber stimulations significantly increased the number of pERK-positive neurons in
      the superficial spinal dorsal horn, whereas C-fiber stimulation decreased this
      number. The nerve injury-specific pERK increase induced by Abeta-stimulation was
      inhibited by MK-801 and AP-5, but not by CNQX. However, Abeta- and Adelta
      stimulations did not affect the number or size of pERK-positive neurons in the
      dorsal root ganglion, whereas C-fiber-stimulation selectively decreased the
      number of pERK-positive neurons. CONCLUSION: These results suggest that Abeta
      fiber perception is newly transmitted to spinal neurons, which originally receive
      only Adelta- and C-fiber-mediated pain transmission, through NMDA receptor
      mediated mechanisms, in animals with nerve injury. This pharmacological switch in
      Abeta-fiber spinal transmission could be a mechanism underlying neuropathic
      allodynia.

PMID- 18620591
TI  - Hydroxyethyl starch versus Ringer solution in cardiopulmonary bypass prime
      solutions (a randomized controlled trial).
AB  - BACKGROUND: In our study we compared the Ringer solution, which is the standard
      prime solution of our department, with the HES (Hydroxyethyl starch) 130-0.4
      solution, which can be a potential alternative prime solution with an
      indispensable material for the cardio-pulmonary bypass applications. METHODS: 140
      patients undergoing to CABG (Coronary Artery Bypass Graft surgery) were
      electively enrolled to the study. 1500 ml Ringer solution + 200 ml mannitol + 60
      ml sodium bicarbonate + 150 U/kg heparin was used as a prime solution to start
      cardiopulmonary by-pass in 70 patients which was defined as group 1. On the other
      hand, 1500 ml HES 130 - 0.4 + 200 ml mannitol + 60 ml sodium bicarbonate + 150
      U/kg heparin was used as a prime solution in 70 patients in group 2. RESULTS: INR
      (International Normalized Ratio), urea levels and blood platelet counts were
      significantly different between the groups. INR level was higher in group 1,
      while blood urea and creatinine levels and platelet count were higher in group 2
      at the end of the 12th and 24nd hours postoperatively (p = 0.001).In this study,
      it was shown that the usage of HES 130-0.4 as a prime solution did not have
      negative effect on postoperative INR level, platelet count, the need for
      transfusion and the amount of drainage, despite the negative opinions that
      similar solutions caused coagulation disorders. Another interesting result of the
      study was that blood platelet count at 24th hour was statistically significantly
      higher in group 2 (p = 0.001). CONCLUSION: HES 130-0.4 solution is an alternative
      colloidal solution which can be used as the prime solution or as a mixture with
      the crystalloids in cardio-pulmonary bypass applications.

PMID- 18620592
TI  - Post-traumatic tension faecopneumothorax in a young male: case report.
AB  - Diaphragmatic rupture due to trauma is both well recognised and uncommon. The
      difficulties in diagnosing traumatic diaphragmatic rupture at the first admission
      are the most common causes of latent morbidity and mortality. Herniation of the
      abdominal viscera is the most common sequel with strangulation and perforation
      the most serious complication. This case outlines the delayed presentation of
      diaphragmatic rupture and herniation presenting as an acute tension
      faecopneumothorax. We review the relevant literature, with particular emphasis on
      the difficulties in diagnosis at presentation.

PMID- 18620593
TI  - Investigation of 89 candidate gene variants for effects on all-cause mortality
      following acute coronary syndrome.
AB  - BACKGROUND: Many candidate genes have been reported to be risk factors for acute
      coronary syndrome (ACS), but their impact on clinical prognosis following ACS is
      unknown. METHODS: We examined the association of putative genetic risk factors
      with 3-year post-ACS mortality in 811 ACS survivors at university-affiliated
      hospitals in Kansas City, Missouri. Through a systematic literature search, we
      first identified genetic variants reported as susceptibility factors for
      atherosclerosis or ACS. Restricting our analysis to whites, so as to avoid
      confounding from racial admixture, we genotyped ACS cases for 89 genetic variants
      in 72 genes, and performed individual Kaplan-Meier survival analyses. We then
      performed Cox regression to create multivariate risk prediction models that
      further minimized potential confounding. RESULTS: Of 89 variants tested, 16 were
      potentially associated with mortality (P < 0.1 for all), of which 6 were
      significantly associated (P < 0.05) with mortality following ACS. While these
      findings are not more than what would be expected by chance (P = 0.28), even
      after Bonferroni correction and adjustment for traditional cardiac risk factors,
      the IRS1 972Arg variant association (P = 0.001) retained borderline statistical
      significance (P < 0.1). CONCLUSION: With the possible exception of IRS1, we
      conclude that multiple candidate genes were not associated with post-ACS
      mortality in our patient cohort. Because of power limitations, the 16 gene
      variants with P values < 0.1 may warrant further study. Our data do not support
      the hypothesis that the remaining 73 genes have substantial, clinically
      significant association with mortality after an ACS.

PMID- 18620594
TI  - Exploratory study of plasma total homocysteine and its relationship to short-term
      outcome in acute ischaemic stroke in Nigerians.
AB  - BACKGROUND: Hyperhomocysteinemia is a potentially modifiable risk factor for
      stroke, and may have a negative impact on the course of ischaemic stroke. The
      role of hyperhomocysteinemia as it relates to stroke in Africans is still
      uncertain. The objective of this study was to determine the prevalence and short
      term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We
      hypothesized that Hcy levels are significantly higher than in normal controls,
      worsen stroke severity, and increase short-term case fatality rates following
      acute ischaemic stroke. METHODS: The study employed both a case-control and
      prospective follow-up design to study hospitalized adults with first - ever acute
      ischaemic stroke presenting within 48 hours of onset. Clinical histories,
      neurological evaluation (including National Institutes of Health Stroke Scale
      (NIHSS) scores on admission) were documented. Total plasma Hcy was determined on
      fasting samples drawn from controls and stroke cases (within 24 hours of
      hospitalization). Outcome at 4 weeks was assessed in stroke patients using the
      Glasgow Outcome Scale (GOS). RESULTS: We evaluated 155 persons (69 acute
      ischaemic stroke and 86 healthy controls). The mean age +/- SD of the cases was
      58.8 +/- 9.8 years, comparable to that of controls which was 58.3 +/- 9.9 years
      (T = 0.32; P = 0.75). The mean duration of stroke (SD) prior to hospitalization
      was 43.5 +/- 38.8 hours, and mean admission NIHSS score was 10.1 +/- 7.7. Total
      fasting Hcy in stroke patients was 10.2 +/- 4.6 umol/L and did not differ
      significantly from controls (10.1 +/- 3.6 umol/L; P = 0.88).
      Hyperhomocysteinemia, defined by plasma Hcy levels > 90th percentile of controls
      (>14.2 umol/L in women and >14.6 umol/L in men), was present in 7 (10.1%) stroke
      cases and 11 (12.8%) controls (odds ratio 0.86, 95% confidence interval 0.31 -
      2.39; P > 0.05). In multiple regression analysis admission NIHSS score (but not
      plasma Hcy) was a significant determinant of 4 week outcome measured by GOS score
      (P < 0.0001). CONCLUSION: This exploratory study found that homocysteine levels
      are not significantly elevated in Nigerians with acute ischaemic stroke, and
      admission Hcy level is not a determinant of short-term (4 week) stroke outcome.

PMID- 18620595
TI  - Delayed treatment of diagnosed pulmonary tuberculosis in Taiwan.
AB  - BACKGROUND: Mycobacterium tuberculosis infection is an ongoing public health
      problem in Taiwan. The National Tuberculosis Registry Campaign, a case management
      system, was implemented in 1997. This study examined this monitoring system to
      identify and characterize delayed treatment of TB patients. METHODS: Records of
      all tuberculosis cases treated in Taiwan from 2002 through 2005 were obtained
      from the National Tuberculosis Registry Campaign. Initiation of treatment more
      than 7 days after diagnosis was considered a long treatment delay. RESULTS: The
      study included 31,937 patients. The mean day of delayed treatment was 3.6 days.
      Most patients were treated immediately after diagnosis. The relationship between
      number of TB patients and days of delayed treatment after diagnosis exhibited a
      Power-law distribution. The long tail of the power-law distribution indicated
      that an extreme number occur cannot be neglected. Tuberculosis patients treated
      after an unusually long delay require close observation and follow up.
      CONCLUSION: This study found that TB control is generally acceptable in Taiwan;
      however, delayed treatment increases the risk of transmission. Improving the
      protocol for managing confirmed TB cases can minimize disease transmission.

PMID- 18620597
TI  - Severe pulmonary tuberculosis complicating Ileocecal intussusception due to
      intestinal tuberculosis: a case report.
AB  - Adult intussusception is a rare clinical entity that is most often caused by a
      tumor, such as a lipoma, adenoma, or malignant tumor. A case of adult
      intussusception due to intestinal tuberculosis of the ileocecal region is
      reported. There are few cases of intussusception due to intestinal tuberculosis.

PMID- 18620596
TI  - Ultrasound properties of articular cartilage in the tibio-femoral joint in knee
      osteoarthritis: relation to clinical assessment (International Cartilage Repair
      Society grade).
AB  - INTRODUCTION: There is a lack of data relating the macroscopic appearance of
      cartilage to its ultrasound properties. The purpose of the present study was to
      evaluate degenerated cartilage and healthy-looking cartilage using an ultrasound
      system. METHODS: Ultrasound properties--signal intensity (a measure of
      superficial cartilage integrity), echo duration (a parameter related to the
      surface irregularity) and the interval between signals (that is, time of flight-
      which is related to the thickness and ultrasound speed of cartilage)--of 20 knees
      were measured at seven sites: the lateral femoral condyle (site A, anterior; site
      B, posterior), the medial condyle (site C), the lateral tibial plateau (site D,
      center; site E, under the meniscus) and the medial tibial plateau (site F,
      anterior; site G, posterior). The sites were evaluated macroscopically and
      classed using the International Cartilage Repair Society (ICRS) grading system.
      RESULTS: The signal intensity of grade 0 cartilage was significantly greater than
      the intensities of grade 1, grade 2 or grade 3 cartilage. Signal intensity
      decreased with increasing ICRS grades. The signal intensity was greater at site B
      than at site C, site D, site F and site G. The signal intensity of grade 0 was
      greater at site B than at site E. The echo duration did not differ between the
      grades and between the sites. The interval between signals of grade 3 was less
      than the intervals of grade 0, grade 1 or grade 2. The interval between signals
      at site C was less than the intervals at site A, site B, site D, and site E.
      CONCLUSION: Site-specific differences in signal intensity suggest that a
      superficial collagen network may be maintained in cartilage of the lateral
      condyle but may deteriorate in cartilage of the medial condyle and the medial
      tibial plateau in varus knee osteoarthritis. Signal intensity may be helpful to
      differentiate ICRS grades, especially grade 0 cartilage from grade 1 cartilage.

PMID- 18620599
TI  - GenCLiP: a software program for clustering gene lists by literature profiling and
      constructing gene co-occurrence networks related to custom keywords.
AB  - BACKGROUND: Biomedical researchers often want to explore pathogenesis and
      pathways regulated by abnormally expressed genes, such as those identified by
      microarray analyses. Literature mining is an important way to assist in this
      task. Many literature mining tools are now available. However, few of them allows
      the user to make manual adjustments to zero in on what he/she wants to know in
      particular. RESULTS: We present our software program, GenCLiP (Gene Cluster with
      Literature Profiles), which is based on the methods presented by Chaussabel and
      Sher (Genome Biol 2002, 3(10):RESEARCH0055) that search gene lists to identify
      functional clusters of genes based on up-to-date literature profiling. Four
      features were added to this previously described method: the ability to 1)
      manually curate keywords extracted from the literature, 2) search genes and gene
      co-occurrence networks related to custom keywords, 3) compare analyzed gene
      results with negative and positive controls generated by GenCLiP, and 4)
      calculate probabilities that the resulting genes and gene networks are randomly
      related. In this paper, we show with a set of differentially expressed genes
      between keloids and normal control, how implementation of functions in GenCLiP
      successfully identified keywords related to the pathogenesis of keloids and
      unknown gene pathways involved in the pathogenesis of keloids. CONCLUSION: With
      regard to the identification of disease-susceptibility genes, GenCLiP allows one
      to quickly acquire a primary pathogenesis profile and identify pathways involving
      abnormally expressed genes not previously associated with the disease.

PMID- 18620598
TI  - The Procalcitonin And Survival Study (PASS) - a randomised multi-center
      investigator-initiated trial to investigate whether daily measurements biomarker
      Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal
      Procalcitonin levels, can improve survival in intensive care unit patients.
      Calculated sample size (target population): 1000 patients.
AB  - BACKGROUND: Sepsis and complications to sepsis are major causes of mortality in
      critically ill patients. Rapid treatment of sepsis is of crucial importance for
      survival of patients. The infectious status of the critically ill patient is
      often difficult to assess because symptoms cannot be expressed and signs may
      present atypically. The established biological markers of inflammation
      (leucocytes, C-reactive protein) may often be influenced by other parameters than
      infection, and may be unacceptably slowly released after progression of an
      infection. At the same time, lack of a relevant antimicrobial therapy in an early
      course of infection may be fatal for the patient. Specific and rapid markers of
      bacterial infection have been sought for use in these patients. METHODS: Multi
      centre randomized controlled interventional trial. Powered for superiority and
      non-inferiority on all measured end points. Complies with, "Good Clinical
      Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion:
      1) Age > or = 18 years of age, 2) Admitted to the participating intensive care
      units, 3) Signed written informed consent.Exclusion: 1) Known hyper
      bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by
      blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two
      arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and
      Procalcitonin guided diagnostics and treatment of infection. Primary Trial
      Objective: To address whether daily Procalcitonin measurements and immediate
      diagnostic and therapeutic response on day-to-day changes in procalcitonin can
      reduce the mortality of critically ill patients. DISCUSSION: For the first time
      ever, a mortality-endpoint, large scale randomized controlled trial with a
      biomarker-guided strategy compared to the best standard of care, is conducted in
      an Intensive care setting. Results will, with a high statistical power answer the
      question: Can the survival of critically ill patients be improved by actively
      using biomarker procalcitonin in the treatment of infections? 700 critically ill
      patients are currently included of 1000 planned (June 2008). Two interim analyses
      have been passed without any safety or futility issues, and the third interim
      analysis is soon to take place. Trial registration number at clinicaltrials.gov:
      Id. nr.: NCT00271752).

PMID- 18620600
TI  - Experimental insight into the proximate causes of male persistence variation
      among two strains of the androdioecious Caenorhabditis elegans (Nematoda).
AB  - BACKGROUND: In the androdioecious nematode Caenorhabditis elegans virtually all
      progeny produced by hermaphrodite self-fertilization is hermaphrodite while 50%
      of the progeny that results from cross-fertilization by a male is male. In the
      standard laboratory wild type strain N2 males disappear rapidly from populations.
      This is not the case in some other wild type isolates of C. elegans, among them
      the Hawaiian strain CB4856. RESULTS: We determined the kinetics of the loss of
      males over time for multiple population sizes and wild isolates and found
      significant differences. We performed systematic inter- and intra-strain crosses
      with N2 and CB4856 and show that the males and the hermaphrodites contribute to
      the difference in male maintenance between these two strains. In particular,
      CB4856 males obtained a higher number of successful copulations than N2 males and
      sired correspondingly more cross-progeny. On the other hand, N2 hermaphrodites
      produced a higher number of self-progeny, both when singly mated and when not
      mated. CONCLUSION: These two differences have the potential to explain the
      observed variation in male persistence, since they should lead to a predominance
      of self-progeny (and thus hermaphrodites) in N2 and, at the same time, a high
      proportion of cross-progeny (and thus the presence of males as well as
      hermaphrodites) in CB4856.

PMID- 18620601
TI  - Analysis of transient phosphorylation-dependent protein-protein interactions in
      living mammalian cells using split-TEV.
AB  - BACKGROUND: Regulated protein-protein interactions (PPIs) are pivotal molecular
      switches that are important for the regulation of signaling processes within
      eukaryotic cells. Cellular signaling is altered in various disease conditions and
      offers interesting options for pharmacological interventions. Constitutive PPIs
      are usually mediated by large interaction domains. In contrast, stimulus
      regulated PPIs often depend on small post-translational modifications and are
      thus better suited targets for drug development. However, the detection of
      modification-dependent PPIs with biochemical methods still remains a labour- and
      material-intensive task, and many pivotal PPIs that are potentially suited for
      pharmacological intervention most likely remain to be identified. The
      availability of methods to easily identify and quantify stimulus-dependent,
      potentially also transient interaction events, is therefore essential. The assays
      should be applicable to intact mammalian cells, optimally also to primary cells
      in culture. RESULTS: In this study, we adapted the split-TEV system to quantify
      phosphorylation-dependent and transient PPIs that occur at the membrane and in
      the cytosol of living mammalian cells. Split-TEV is based on a PPI-induced
      functional complementation of two inactive TEV protease fragments fused to
      interaction partners of choice. Genetically encoded transcription-coupled and
      proteolysis-only TEV reporter systems were used to convert the TEV activity into
      an easily quantifiable readout. We measured the phosphorylation-dependent
      interaction between the pro-apoptotic protein Bad and the adapter proteins 14-3
      3epsilon and zeta in NIH-3T3 fibroblasts and in primary cultured neurons. Using
      split-TEV assays, we show that Bad specifically interacts with 14-3-3 isoforms
      when phosphorylated by protein kinase Akt-1/PKB at Ser136. We also measured the
      phosphorylation-dependent Bad/14-3-3 interactions mediated by endogenous and
      transient Akt-1 activity. We furthermore applied split-TEV assays to measure the
      phosphorylation-dependent interactions of Neuregulin-1-stimulated ErbB4 receptors
      with several adapter proteins. CONCLUSION: Split-TEV assays are well suited to
      measure phosphorylation-dependent and transient PPIs that occur specifically at
      the membrane and in the cytosol of heterologous and primary cultured mammalian
      cells. Given the high sensitivity of the split-TEV system, all assays were
      performed in multi-plate formats and could be adapted for higher throughput to
      screen for pharmacologically active substances.

PMID- 18620602
TI  - A systems approach to model natural variation in reactive properties of bacterial
      ribosomes.
AB  - BACKGROUND: Natural variation in protein output from translation in bacteria and
      archaea may be an organism-specific property of the ribosome. This paper adopts a
      systems approach to model the protein output as a measure of specific ribosome
      reactive properties in a ribosome-mediated translation apparatus. We use the
      steady-state assumption to define a transition state complex for the ribosome,
      coupled with mRNA, tRNA, amino acids and reaction factors, as a subsystem that
      allows a focus on the completed translational output as a measure of specific
      properties of the ribosome. RESULTS: In analogy to the steady-state reaction of
      an enzyme complex, we propose a steady-state translation complex for mRNA from
      any gene, and derive a maximum specific translation activity, Ta(max), as a
      property of the ribosomal reaction complex. Ta(max) has units of a-protein output
      per time per a-specific mRNA. A related property of the ribosome, T a(max), has
      units of a-protein per time per total RNA with the relationshipT a(max) =
      rho(a)Ta(max), where rho(a) represents the fraction of total RNA committed to
      translation outpout of P(a) from gene a message. Ta(max) as a ribosome property
      is analogous to k(cat) for a purified enzyme, and Ta(max) is analogous to enzyme
      specific activity in a crude extract. CONCLUSION: Analogy to an enzyme reaction
      complex led us to a ribosome reaction model for measuring specific translation
      activity of a bacterial ribosome. We propose to use this model to design
      experimental tests of our hypothesis that specific translation activity is a
      ribosomal property that is subject to natural variation and natural selection
      much like Vmax and Km for any specific enzyme.

PMID- 18620603
TI  - Adrenocortical oncocytic neoplasm presenting with Cushing's syndrome: a case
      report.
AB  - INTRODUCTION: Oncocytic neoplasms occur in several organs and are most commonly
      found in the thyroid, kidneys and salivary glands. Oncocytic neoplasms of the
      adrenal cortex are extremely rare and are usually non-functioning. CASE
      PRESENTATION: We report the case of an adrenocortical oncocytic neoplasm with
      uncertain malignant potential in a 31-year-old man with Cushing's syndrome. The
      patient had been operated on following diagnosis of a 7 cm adrenal mass.
      Following surgery, the Cushing's syndrome resolved. The patient is still alive
      with no metastases one year after the surgery. CONCLUSION: Adrenocortical
      oncocytic neoplasms must be considered in the differential diagnosis of both
      functioning and non-functioning adrenal masses.

PMID- 18620604
TI  - PRESTO: rapid calculation of order statistic distributions and multiple-testing
      adjusted P-values via permutation for one and two-stage genetic association
      studies.
AB  - BACKGROUND: Large-scale genetic association studies can test hundreds of
      thousands of genetic markers for association with a trait. Since the genetic
      markers may be correlated, a Bonferroni correction is typically too stringent a
      correction for multiple testing. Permutation testing is a standard statistical
      technique for determining statistical significance when performing multiple
      correlated tests for genetic association. However, permutation testing for large
      scale genetic association studies is computationally demanding and calls for
      optimized algorithms and software. PRESTO is a new software package for genetic
      association studies that performs fast computation of multiple-testing adjusted P
      values via permutation of the trait. RESULTS: PRESTO is an order of magnitude
      faster than other existing permutation testing software, and can analyze a large
      genome-wide association study (500 K markers, 5 K individuals, 1 K permutations)
      in approximately one hour of computing time. PRESTO has several unique features
      that are useful in a wide range of studies: it reports empirical null
      distributions for the top-ranked statistics (i.e. order statistics), it performs
      user-specified combinations of allelic and genotypic tests, it performs
      stratified analysis when sampled individuals are from multiple populations and
      each individual's population of origin is specified, and it determines
      significance levels for one and two-stage genotyping designs. PRESTO is designed
      for case-control studies, but can also be applied to trio data (parents and
      affected offspring) if transmitted parental alleles are coded as case alleles and
      untransmitted parental alleles are coded as control alleles. CONCLUSION: PRESTO
      is a platform-independent software package that performs fast and flexible
      permutation testing for genetic association studies. The PRESTO executable file,
      Java source code, example data, and documentation are freely available at
      http://www.stat.auckland.ac.nz/~browning/presto/presto.html.

PMID- 18620605
TI  - The association of APOE genotype and cognitive decline in interaction with risk
      factors in a 65-69 year old community sample.
AB  - BACKGROUND: While the evidence of an association between the apolipoprotein E
      (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4
      allele on cognitive decline in the general population is more equivocal. A cross
      sectional study on the lifespan effects of the *E4 allele 1 failed to find any
      effect of the *E4 allele on cognitive performance at ages 20-24, 40-44 or 60-64
      years. METHODS: In this four year follow-up study, we reexamine the effect of *E4
      in the sample of 2,021 individuals, now aged 65-69 years. RESULTS: Performance on
      the Mini-Mental State Examination (MMSE) was significantly poorer for *E4
      homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype
      on cognitive decline over four years were found on the MMSE and Symbol-Digit
      Modalities test but only when controlling for risk factors such as head injury
      and education. Analyses were repeated with the exclusion of participants
      diagnosed with a mild cognitive disorder, with little change. CONCLUSION: It is
      possible that *E4 carriers become vulnerable to greater cognitive decline in the
      presence of other risk factors at 65-69 years of age.

PMID- 18620606
TI  - Gonadotropin-releasing hormone agonist use in men without a cancer registry
      diagnosis of prostate cancer.
AB  - BACKGROUND: Use of gonadotropin-releasing hormone (GnRH) agonists has become
      popular for virtually all stages of prostate cancer. We hypothesized that some
      men receive these agents after only a limited work-up for their cancer. Such
      cases may be missed by tumor registries, leading to underestimates of the total
      extent of GnRH agonist use. METHODS: We used linked Surveillance, Epidemiology
      and End-Results (SEER)-Medicare data from 1993 through 2001 to identify GnRH
      agonist use in men with either a diagnosis of prostate cancer registered in SEER,
      or with a diagnosis of prostate cancer based only on Medicare claims (from the 5%
      control sample of Medicare beneficiaries residing in SEER areas without a
      registered diagnosis of cancer). The proportion of incident GnRH agonist users
      without a registry diagnosis of prostate cancer was calculated. Factors
      associated with lack of a registry diagnosis were examined in multivariable
      analyses. RESULTS: Of incident GnRH agonist users, 8.9% had no diagnosis of
      prostate cancer registered in SEER. In a multivariable logistic regression model,
      lack of a registry diagnosis of prostate cancer in GnRH agonist users was
      significantly more likely with increasing comorbidity, whereas it was less likely
      in men who had undergone either inpatient admission or procedures such as radical
      prostatectomy, prostate biopsy, or transurethral resection of the prostate.
      CONCLUSION: Reliance solely on tumor registry data may underestimate the rate of
      GnRH agonist use in men with prostate cancer.

PMID- 18620608
TI  - The risk of pathogenic intestinal parasite infections in Kisii Municipality,
      Kenya.
AB  - BACKGROUND: Intestinal parasitic infections are among the most common infections
      worldwide. Various epidemiological studies indicate that the prevalence of
      intestinal parasites is high especially in developing countries, although in many
      of these, the environmental risk factors have not been clearly elucidated. The
      objective of this study was to determine the risk of pathogenic intestinal
      parasites infections in Kisii Municipality. METHODS: Random sampling was used in
      the selection of the study samples. Stool parasitological profiles of food
      handlers were done by direct smear and formalin-ethyl acetate sedimentation
      method. Both vegetable and meat samples were examined for the presence of
      intestinal parasites. The storage and meat handling practices of the various
      butcheries were observed. RESULTS: Types of samples examined for occurrence of
      intestinal parasites includes, a total of 84 vegetable, 440 meat and 168 stool
      samples. Fifty five (65.5%) vegetable, 334 (75.9%) meat and 69 (41.1%) of the
      stool samples were found positive for intestinal parasites indicating a high
      overall risk (66.18%) for intestinal parasite infections. Of the parasites
      detected, the most common parasites infesting the foodstuffs and infecting the
      food handlers were Ascaris lumbricoides and Entamoeba histolytica. Parasites were
      significantly less likely to be present on meat that was refrigerated during
      display than meat that was displayed at ambient temperature. CONCLUSION: There is
      a high risk of infection with intestinal parasites in the sampled Municipal
      markets. About half of the food handlers surveyed (41.1 %) at the Municipal
      Hospital had one or more parasitic infections. Furthermore, meat (65.5%) and
      vegetables (75.9%) sold at the Municipal market were found to be contaminated
      with parasites hence the inhabitants requires a need for education on food
      safety, good distribution practices and improvement on sanitary conditions.

PMID- 18620607
TI  - Fragmentation of decorin, biglycan, lumican and keratocan is elevated in
      degenerate human meniscus, knee and hip articular cartilages compared with age
      matched macroscopically normal and control tissues.
AB  - INTRODUCTION: The small leucine-rich proteoglycans (SLRPs) modulate tissue
      organization, cellular proliferation, matrix adhesion, growth factor and cytokine
      responses, and sterically protect the surface of collagen type I and II fibrils
      from proteolysis. Catabolism of SLRPs has important consequences for the
      integrity of articular cartilage and meniscus by interfering with their tissue
      homeostatic functions. METHODS: SLRPs were dissociatively extracted from
      articular cartilage from total knee and hip replacements, menisci from total knee
      replacements, macroscopically normal and fibrillated knee articular cartilage
      from mature age-matched donors, and normal young articular cartilage. The tissue
      extracts were digested with chondroitinase ABC and keratanase-I before
      identification of SLRP core protein species by Western blotting using antibodies
      to the carboxyl-termini of the SLRPs. RESULTS: Multiple core-protein species were
      detected for all of the SLRPs (except fibromodulin) in the degenerate
      osteoarthritic articular cartilage and menisci. Fibromodulin had markedly less
      fragments detected with the carboxyl-terminal antibody compared with other SLRPs.
      There were fewer SLRP catabolites in osteoarthritic hip than in knee articular
      cartilage. Fragmentation of all SLRPs in normal age-matched, nonfibrillated knee
      articular cartilage was less than in fibrillated articular cartilage from the
      same knee joint or total knee replacement articular cartilage specimens of
      similar age. There was little fragmentation of SLRPs in normal control knee
      articular cartilage. Only decorin exhibited a consistent increase in
      fragmentation in menisci in association with osteoarthritis. There were no
      fragments of decorin, biglycan, lumican, or keratocan that were unique to any
      tissue. A single fibromodulin fragment was detected in osteoarthritic articular
      cartilage but not meniscus. All SLRPs showed a modest age-related increase in
      fragmentation in knee articular and meniscal cartilage but not in other tissues.
      CONCLUSION: Enhanced fragmentation of SLRPs is evident in degenerate articular
      cartilage and meniscus. Specific decorin and fibromodulin core protein fragments
      in degenerate meniscus and/or human articular cartilage may be of value as
      biomarkers of disease. Once the enzymes responsible for their generation have
      been identified, further research may identify them as therapeutic targets.

PMID- 18620609
TI  - Early distant relapse after optimal local control in locally advanced rectal
      cancer.
AB  - We present a case of locally advanced rectal cancer with initial optimal local
      control after neoadjuvant concurrent chemoradiotherapy followed by surgery; early
      liver recurrence then occurred and was treated again with curative intent with
      neoadjuvant combination chemotherapy followed by liver surgery. We reflect on
      this difficult problem and discuss relevant topics to this case report.

PMID- 18620610
TI  - Performance of self-diagnosis and standby treatment of malaria in international
      oilfield service employees in the field.
AB  - BACKGROUND: Falciparum malaria remains a major occupational illness that accounts
      for several deaths per year and numerous lost working days among the expatriate
      population, working or living in high-risk malarious areas. Compliance to
      preventive strategies is poor in travellers, especially business travellers,
      expatriates and long-term travellers. METHODS: In this cross-sectional, web-based
      study the adherence to and outcome of a preventive malaria programme on
      knowledge, attitudes and practices, including the practice of self-diagnosis and
      standby treatment (curative malaria kit, CMK) was evaluated in 2,350 non-immune
      expatriates, who had been working in highly malaria endemic areas. RESULTS: One
      third (N = 648) of these expatriates visited a doctor for malaria symptoms and
      almost half (29 of 68) of all hospitalizations were due to malaria. The mandatory
      malaria training for non-immunes was completed by 92% of those who visited or
      worked in a high risk malaria country; 70% of the respondents at risk also
      received the CMK. The malaria awareness training and CMK significantly increased
      malaria knowledge [relative risk (RR) of 1.5, 95%CI 1.2-2.1], attitudes and
      practices, including compliance to chemoprophylaxis [RR = 2.2, 95%CI 1.6-3.2].
      Hospitalization for malaria tended to be reduced by the programme [RR = 0.4,
      95%CI 0.1-1.1], albeit not significantly. Respondents who did not receive
      instructions on the rapid diagnostic test were two times [RR = 2.3, 95%CI 1.6
      3.3] more likely to have difficulties. Those who did receive instructions adhered
      poorly to the timing of repeating the test. Moreover, 6% (31 of 513) of those
      with a negative test result were diagnosed with malaria by a local doctor. 77% (N
      = 393) of the respondents with a negative test result did not take curative
      medication. 57% (252 of 441) of the respondents who took the curative medication
      that was included in the kit did not have a positive self-test or clinical
      malaria diagnosis made by a doctor. CONCLUSION: This survey demonstrated that a
      comprehensive programme targeting malaria prevention in expatriates can be
      effectively implemented and that it significantly increased malaria awareness.

PMID- 18620611
TI  - Determinants of low birth weight in urban Pakistan.
AB  - OBJECTIVE: To identify determinants of low birth weight (LBW) in Karachi,
      Pakistan, including environmental exposures and nutritional status of the mother
      during pregnancy. DESIGN: Cross-sectional study.ParticipantsFive hundred and
      forty mother-infant pairs. We interviewed mothers about obstetric history, diet
      and exposure to Pb. We measured birth weight and blood lead level (BLL). We
      performed multiple log binomial regression analysis to identify factors related
      to LBW. RESULTS: Of 540 infants, 100 (18.5 %) weighed <or=2.5 kg. Umbilical cord
      BLL was not significantly associated with LBW. Maternal poor self-rated health
      (adjusted prevalence ratio (adjPR) = 1.83; 95 % CI 1.09, 3.07) and none or one
      prenatal visit (adjPR = 2.18; 95 % CI 1.39, 3.43) were associated with LBW. A
      statistically significant interaction between mothers' mid upper-arm
      circumference (MUAC) and dietary vitamin C intake was noted. Compared with
      mothers with MUAC above the median and dietary vitamin C intake above the 3rd
      quartile (>208.7 mg/d), infants of mothers with MUAC less than or equal to the
      median and dietary vitamin C intake >208.7 mg/d (adjPR = 10.80; 95 % CI 1.46,
      79.76), mothers with MUAC above the median and vitamin C intake <or=208.7 mg/d
      (adjPR = 10.67; 95 % CI 1.50, 76.02) and mothers with MUAC less than or equal to
      the median and vitamin C intake <or=208.7 mg/d (adjPR = 13.19; 95 % CI 1.85,
      93.79) more likely to give birth to an LBW infant. CONCLUSIONS: In Pakistan, poor
      nutritional status and inadequate prenatal care were major determinants of LBW in
      this setting. Environmental factors including umbilical cord BLL were not
      significantly associated with LBW.

PMID- 18620612
TI  - Measurement of macular pigment optical density and distribution using the steady
      state visual evoked potential.
AB  - The purpose of this study was to specify isoluminance at different retinal
      eccentricities and to characterize macular pigment optical density (MPOD) and
      distribution using the steady-state visual evoked potential (VEP). Redgreen (B/G)
      gratings were generated within two circular stimulus fields (radius = 0.55 or 1.1
      deg) and within four annular fields (maximum mean radius = 6.0 deg) on a color
      monitor. Temporal frequency was 15 Hz. Isoluminance was determined for each
      stimulus using minimum flicker photometry. Steady-state onset-offset VEPs were
      recorded to the same annular stimuli as the luminance ratio between adjacent
      chromatic components was changed from 0.25 to 0.85 in 11 automated steps (0.5
      representing photometric isoluminance). Fourier analysis showed that the power of
      the first harmonic was minimized at the isoluminant ratio specific to each
      subject. Relative OD was computed by comparing the isoluminant ratio at any
      location with that for the most eccentric annulus. To compensate for the
      broadband characteristics of the monitor, OD values were corrected according to
      minimum flicker measurements made through known concentrations of carotenoid
      solution. MPOD was additionally measured using minimum motion photometry.There
      was high correlation between the isoluminant ratios determined by minimum flicker
      and VEPs for both R/G and B/G stimulation (r = 0.91, P < 0.005, slope = 1).
      Calibrated OD values computed from VEP estimates of B/G isoluminance correlated
      with those derived from minimum flicker (r = 0.96, P < 0.0005, slope = 0.85) and
      motion photometry (r = 0.94, P < 0.0005, slope = 0.88). OD values derived from
      B/G VEPs increased toward the fovea and corresponded closely with minimum flicker
      and minimum motion assessment of MP distribution profiles. The steady-state VEP
      can be used to determine isoluminance at different retinal eccentricities. MPOD
      and distribution can be measured by steady-state VEPs to B/G stimuli.

PMID- 18620614
TI  - Antihypertensive effect of an angiotensin converting enzyme inhibitory peptide
      from enzyme modified cheese.
AB  - Two angiotensin converting enzyme (ACE)-inhibitory peptides were isolated from
      enzyme modified cheese (EMC) and their amino acid sequences were identified as
      Leu-Gln-Pro and Met-Ala-Pro. The EMC was prepared by a combination of Protease N,
      Umamizyme, and Flavourzyme 500L. Both peptides were derived from beta-casein, f
      88-90 and f 102-104, respectively. Met-Ala-Pro showed strong ACE inhibitory
      activity (IC50=0.8 mum) and antihypertensive activity in spontaneously
      hypertensive rats (SHR) after single oral administration. The IC50 value of Met
      Ala-Pro was not affected by pre-incubation with ACE, suggesting that this peptide
      was a true ACE-inhibitory peptide. We report here, for the first time
      antihypertensive peptides from EMC.

PMID- 18620613
TI  - Molecular pathogenesis and clinical implications of eczema herpeticum.
AB  - A subgroup of patients with atopic dermatitis develops one or more episodes of a
      severe viral skin infection caused by herpes simplex virus superimposed on
      eczematous skin lesions. This condition is named atopic dermatitis complicated by
      eczema herpeticum. Characteristic features of patients developing eczema
      herpeticum include an early age of onset of atopic dermatitis with a persistent
      and severe course into adulthood, predilection for eczematous skin lesions in the
      head and neck area, elevated total serum IgE levels and increased allergen
      sensitisation. Deficiencies at the level of both the innate and the adaptive
      immune system, which have been identified in atopic dermatitis, are much more
      pronounced in this subgroup. Predisposing cellular factors include a reduced
      number of plasmacytoid dendritic cells in the epidermis and a modified capacity
      of these cells to produce type I interferons after allergen challenge. In
      addition, lower levels of antimicrobial peptides in the skin of atopic dermatitis
      patients, resulting in part from a Th2-prone micromilieu, contribute to the lack
      of an effective defence against viral attack. In this review, we summarise the
      current knowledge of the molecular pathogenesis of eczema herpeticum.

PMID- 18620615
TI  - Changes in the surface protein of the fat globules during homogenization and heat
      treatment of concentrated milk.
AB  - The changes in milk fat globules and fat globule surface proteins of both low
      preheated and high-preheated concentrated milks, which were homogenized at low or
      high pressure, were examined. The average fat globule size decreased with
      increasing homogenization pressure. The total surface protein (mg m-2) of
      concentrated milk increased after homogenization, the extent of the increase
      being dependent on the temperature and the pressure of homogenization, as well as
      on the preheat treatment. The concentrates obtained from high-preheated milks had
      higher surface protein concentration than the concentrates obtained from low
      preheated milks after homogenization. Concentrated milks heat treated at 79
      degrees C either before or after homogenization had greater amounts of fat
      globule surface protein than concentrated milks heat treated at 50 or 65 degrees
      C. This was attributed to the association of whey protein with the native MFGM
      (milk fat globule membrane) proteins and the adsorbed skim milk proteins. Also,
      at the same homogenization temperature and pressure, the amount of whey protein
      on the fat globule surface of the concentrated milk that was heated after
      homogenization was greater than that of the concentrated milk that was heated
      before homogenization. The amounts of the major native MFGM proteins did not
      change during homogenization, indicating that the skim milk proteins did not
      displace the native MFGM proteins but adsorbed on to the newly formed surface.

PMID- 18620616
TI  - Butter making from caprine creams: effect of washing treatment on phospholipids
      and milk fat globule membrane proteins distribution.
AB  - A washing treatment was applied to caprine cream before churning in order to
      improve phospholipids and MFGM protein purification from buttermilk and butter
      serum. Cream obtained from a first separation was diluted with water and
      separated a second time using pilot plant equipment. Regular and washed creams
      were churned to produce buttermilk and butter, from which butter serum was
      extracted. The washing treatment allowed a significant decrease of the casein
      content. As a result, the phospholipids-to-protein ratios in washed buttermilk
      and butter serum were markedly increased by 2.1 and 1.7-folds respectively, which
      represents an advantage for the production of phospholipids concentrates.
      However, when compared with bovine cream, lower phospholipids-to-protein ratios
      were observed when the washing treatment was applied to caprine cream. A higher
      concentration of MFGM protein and a lower retention of phospholipids during
      washing treatment are responsible for the lower phospholipids-to-protein ratios
      in buttermilk and butter serum obtained from caprine cream. The phospholipids
      distribution in the butter making process was similar to the one obtained from
      bovine regular and washed cream. Phospholipids were preferentially concentrated
      in the butter serum rather than the buttermilk fraction. This simple approach
      permitted the production of caprine and bovine butter sera extracts containing up
      to 180 and 240 g phospholipids/kg sera, respectively, on a dry basis.

PMID- 18620617
TI  - The rebodying of stirred yoghurt: interactions between proteins.
AB  - The aim of the present study was to identify the nature of bonds established
      between protein particles after stirring that are responsible for the texture
      improvement of stirred yoghurts, called rebodying. Using a constant model yoghurt
      at pH 4.4, the effects of changes in the physicochemical conditions at stirring
      were studied on the subsequent rebodying. Short term rebodying was measured as
      the changes in viscoelastic properties at 4 degrees C during 20 h after stirring,
      while long-term rebodying was measured as the viscosity changes during 28 d
      storage at 4 degrees C. Moreover, stirred gels obtained from either set gels that
      were allowed time or not for ionic equilibration were compared. Increasing or
      decreasing ionic strength did not change the properties of stirred gels. Calcium
      chloride addition significantly decreased G'0 h, G'20 h and tan20 h but did not
      induce changes in the gel microstructure as observed by confocal scanning
      microscopy. Yoghurt rebodying could not be explained by fulfilling ionic
      equilibrium. Moreover, N-ethyl maleimide addition had no effect on the stirred
      yoghurt. Attractive electrostatic and disulphide interactions were not involved
      in the gel rebodying and increasing calcium concentration in the set gel limited
      rebodying.

PMID- 18620618
TI  - Molecular methods for identification of Lactobacillus delbrueckii subsp.
      bulgaricus and Streptococcus thermophilus using methionine biosynthesis and 16S
      rRNA genes.
AB  - Yoghurt and starter culture producers are still searching strains of
      Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus to
      produce healthier yogurt with longer shelf life, better texture, taste and
      quality. However, selective identification of Lb. delbrueckii subsp. bulgaricus
      and Strep. thermophilus from a mixed population using microbiological and
      biochemical methods is difficult, time consuming and may not be accurate. In this
      study, a quick, sensitive and accurate method is proposed to identify both Lb.
      delbrueckii subsp. bulgaricus and Strep. thermophilus using PCR. The method is
      comprised of two parts. In the first part, methionine biosynthesis genes, known
      to be present in both species were partially amplified by designed primers
      (cysmet2F and cysmet2R). Partial amplification of the methionine biosynthesis
      gene which gives 700 bp fragment resulted in selective identification of Lb.
      bulgaricus and Strep. thermophilus. All 16 Lb. bulgaricus and 6 Strep.
      thermophilus isolates assessed by this method gave the expected amplification. On
      the other hand, further analysis of other closely related species with the same
      primers have indicated that the same product was also amplified in two more
      lactobacilli namely, Lb. delbrueckii subsp. lactis and Lb. helveticus species.
      Thus, in the second part of the method, further differentiation of Lb.
      delbrueckii subsp. bulgaricus and Strep. thermophilus from each other and these
      species was achieved using restriction analysis of 16S rRNA gene with EcoRI.

PMID- 18620619
TI  - Protease expression analysis in recently field-isolated strains of Trypanosoma
      cruzi: a heterogeneous profile of cysteine protease activities between TC I and
      TC II major phylogenetic groups.
AB  - Protease expression among TCI and TCII field isolates was analysed. Gelatin
      containing gels revealed hydrolysis bands with molecular masses ranging from 45
      to 66 kDa. The general protease expression profile showed that TCII isolates
      presented higher heterogeneity compared to TCI. By utilizing protease inhibitors,
      we showed that all active proteases at acid pH are cysteine-proteases and all
      proteases active at alkaline pH are metalloproteases. However, the expression of
      cruzipain, the T. cruzi major cysteine-protease, did not reproduce a
      heterogeneous TCII cysteine zymogram profile. Dendogram analyses based on
      presence/absence matrices of proteases and cruzipain bands showed a TCI
      separation from the TCII group with 50-60% similarity. We suggest that the
      observed cysteine protease diversification contributes to differential host
      infection between TCI and II genotypes.

PMID- 18620620
TI  - Immunolocalization of Taenia solium gap junction innexins.
AB  - In previous studies, ultrastructural observations revealed a large number of gap
      junctions (GJs) in the neck and immature proglottid tissues of Taenia solium
      tapeworms. In these helminths, cytoplasmic glycogen sacs are connected by
      numerous discrete GJs to other cells throughout the maturing strobilar tissue.
      Discontinuous sucrose gradients were used to purify membrane fractions containing
      GJs, which were identified by ultrastructural analysis. A trans-membrane peptide
      sequence from a highly conserved innexin region was used to construct a 20-amino
      acid synthetic peptide and used to raise polyclonal antibodies in rabbits that
      recognized both a 55 and a 67 kDa protein in a Western blot of the GJ-enriched
      pellet. Immunohistochemistry of larval and adult worm sections incubated with
      antiserum to the synthetic peptide and a secondary anti-rabbit IgG bound to
      fluorescein, revealed strong binding to the tegumentary surface of the worm, as
      well as patchy fluorescent areas in the parenchyma. The results indicate that
      both the tegument of cysticerci and adult T. solium contain innexin-rich
      membranes, which may function as a tegumentary transport system for small
      molecules.

PMID- 18620621
TI  - Were class C iron-containing superoxide dismutases of trypanosomatid parasites
      initially imported into a complex plastid? A hypothesis based on analyses of
      their N-terminal targeting signals.
AB  - Trypanosomatid parasites possess 2 distinct iron-containing superoxide dismutases
      (Fe-SODs) designated SODA and SODC, both of which are targeted to their
      mitochondria. In contrast to SODAs that carry typical mitochondrial transit
      peptides, SODCs have highly unusual mitochondrial targeting signals. Our analyses
      clearly show that these pre-sequences are bipartite possessing a signal peptide
      like domain followed by a transit peptide-like domain. Consequently, they
      resemble N-terminal extensions of proteins targeted to multi-membrane plastids,
      suggesting that trypanosomatids once contained a eukaryotic alga-derived plastid.
      Further support for this hypothesis comes from striking similarities in length,
      hydropathy profile, and amino acid composition of SODC pre-sequences to those of
      Euglena and dinoflagellate plastid proteins. To account for these data, we
      propose that the Trypanosomatidae initially possessed a gene encoding a
      mitochondrial Fe-SOD with a classical mitochondrial transit peptide. Before or
      after plastid acquisition, a gene duplication event gave rise to SODA and SODC.
      In a subsequent evolutionary step a signal peptide was linked to SODC, enabling
      its import into the plastid. When the trypanosomatid plastid subsequently was
      lost, natural selection favoured adaptation of the SODC N-terminal signal as a
      mitochondrial transit peptide and re-targeting to the mitochondrion.

PMID- 18620622
TI  - The distribution of the pathogenic nematode Nematodirus battus in lambs is zero
      inflated.
AB  - Understanding the frequency distribution of parasites and parasite stages among
      hosts is essential for efficient experimental design and statistical analysis,
      and is also required for the development of sustainable methods of controlling
      infection. Nematodirus battus is one of the most important organisms that infect
      sheep but the distribution of parasites among hosts is unknown. An initial
      analysis indicated a high frequency of animals without N. battus and with zero
      egg counts, suggesting the possibility of a zero-inflated distribution. We
      developed a Bayesian analysis using Markov chain Monte Carlo methods to estimate
      the parameters of the zero-inflated negative binomial distribution. The analysis
      of 3000 simulated data sets indicated that this method out-performed the maximum
      likelihood procedure. Application of this technique to faecal egg counts from
      lambs in a commercial upland flock indicated that N. battus counts were indeed
      zero-inflated. Estimating the extent of zero-inflation is important for effective
      statistical analysis and for the accurate identification of genetically resistant
      animals.

PMID- 18620623
TI  - Host-cell apoptosis in Taenia solium-induced brain granulomas in naturally
      infected pigs.
AB  - To assess whether apoptosis occurs in pig brain granulomas due to Taenia solium
      cysticerci, brain tissues from 30 pigs naturally infected with T. solium
      cysticercosis were evaluated by terminal deoxynucleotidyl transferase-end
      labelling (TUNEL) staining. In addition, tissues were stained with CD3 marker to
      identify T lymphocytes. Examination of TUNEL-stained tissues showed apoptotic
      cells in early lesions that contained viable cysticerci. Apoptotic cells were
      primarily found interspersed with normal cell types, and were mostly located in
      the inflammatory infiltrate. Late or advanced granulomas with disintegrated
      scolices did not show TUNEL-positive cells. CD3+ cells were found in both early
      and advanced lesions and apoptosis mainly co-localized with CD3+ T lymphocytes.
      This suggests that these cells are constantly undergoing apoptosis and thus die
      as soon as they arrive at the site of infection. Apoptosis indeed may be one way
      by which T. solium cysticerci down-regulate the host's cellular immune response
      in early cysticercosis. Therefore, further research is needed to establish if
      other cells besides T-lymphocytes are also a target for destruction by cysticerci
      in early cysticercosis as well as studies to assess if cysteine protease is
      expressed by viable cysticerci in situ.

PMID- 18620624
TI  - Specificity of the Toxoplasma gondii-altered behaviour to definitive versus non
      definitive host predation risk.
AB  - The hypothesis that the parasite Toxoplasma gondii manipulates the behaviour of
      its intermediate rat host in order to increase its chance of being predated
      specifically by its feline definitive host, rather than a non-definitive host
      predator species, was tested. The impact of a range of therapeutic drugs,
      previously demonstrated to be effective in preventing the development of T.
      gondii-associated behavioural and cognitive alterations in rats, on definitive
      host predator specificity was also tested. Using a Y-shaped maze design, we
      demonstrated that T. gondii-associated behavioural changes, apparently aimed to
      increase predation rate, do appear to be specific to that of the feline
      definitive host--there were significant and consistent differences between the
      (untreated) infected and uninfected rats groups where T. gondii-infected rats
      tended to choose the definitive host feline-predator-associated maze arm and nest
      box significantly more often than a maze arm or nest-box treated with non
      definitive host predator (mink) odour. Drug treatment of infected rats prevented
      any such host-specificity from being displayed. We discuss our results in terms
      of their potential implications both for T. gondii epidemiology and the evolution
      of parasite-altered behaviour.

PMID- 18620625
TI  - Confirmatory factor analysis of the Revised Scale for Caregiving Self-Efficacy in
      a sample of dementia caregivers.

PMID- 18620626
TI  - Symptomatic remission in elderly schizophrenia patients treated with long-acting
      risperidone.
AB  - BACKGROUND: In elderly schizophrenia patients remission is difficult to determine
      due to long disease duration, exposure to differing treatments, long-standing
      side-effects, non-adherence, cognitive decline and physical comorbidity. METHOD:
      Retrospective chart reviews were undertaken of 48 elderly (60+ years)
      schizophrenia patients admitted to a university-affiliated tertiary psychiatric
      center in 2006. These patients were experiencing an exacerbation of symptoms at
      admission. Remission criteria used were those of the American Psychiatric
      Association's "Remission in Schizophrenia Working Group", and clinical status and
      improvement were quantified using the Clinical Global Impression scale (CGI).
      RESULTS: Of 25 patients treated with long-acting risperidone (LAR), 19 (76%)
      continued uninterrupted treatment for 6 months or longer. In six patients
      treatment was discontinued due to insufficient response. The clinical severity
      ratings with the CGI of all patients were in the range 5-7 prior to treatment.
      Following six months of LAR treatment, mean dose 36.0 mg/2 weeks (range: 25-50),
      18 patients were rated as "improved" or "very much improved" on the CGI-global
      improvement item scale. In 15/25 patients (60%) symptomatic remission was
      achieved. CONCLUSION: LAR may be effective in achieving remission among elderly
      schizophrenia patients. Tolerability was high and adherence rates improved.
      However, the results must be treated with caution owing to the inherent bias in
      this retrospective analysis.

PMID- 18620627
TI  - Evaluation of scimitar syndrome by multislice computed tomography.

PMID- 18620628
TI  - Interaction between the nematophagous fungus Duddingtonia flagrans and infective
      larvae of Haemonchus contortus (Nematoda: Trichostrongyloidea).
AB  - The interaction between Duddingtonia flagrans and infective larvae of Haemonchus
      contortus was studied in vitro under optical and scanning electron microscopy.
      Trap formation by the fungus started 9 hours after inoculation and first larvae
      were found 11 hours after larval inoculation on colonies grown on the surface of
      dialysis membranes. Scanning electron micrographs were taken 12, 24, 36 and 48 h
      after larval predation. Details of predation structures and fungus-larvae
      interaction are described. A mucilaginous substance occurred at the points of
      adherence of traps to nematode cuticle. Bacteria were also found at some points
      of interaction between fungus and larval cuticle. Cuticle penetration by fungus
      hyphae occurred only 48 h after predation.

PMID- 18620629
TI  - Smoking to stay thin or giving up to save face? Young men and women talk about
      appearance concerns and smoking.
AB  - OBJECTIVE: This study was designed to investigate how young men and women smokers
      and non-smokers talk about the impact of smoking on appearance, with the aim of
      using these accounts to inform anti-smoking campaigns targeted at young people.
      DESIGN: Volunteer smokers and non-smokers took part in 24 focus groups. METHOD:
      Eighty-seven men and women aged 17-24 were asked to talk about impacts of smoking
      on appearance. RESULTS: A thematic analysis of transcripts suggested that weight
      gain after quitting was only a significant concern for the younger (17-year-old)
      women. Non-smokers of both genders expressed concern about yellowing of skin and
      teeth if they started smoking, and women non-smokers were concerned about skin
      ageing. Smokers believed that smoking made them look 'cool', mature, and
      sophisticated and would quit only if skin ageing and other negative effects on
      appearance became visible. CONCLUSIONS: Appearance concerns are relevant to the
      decision whether to start and quit smoking, and are linked to gender and age.
      Results are discussed in relation to implications for the development of age- and
      gender-relevant anti-smoking interventions.

PMID- 18620630
TI  - Comment and reply on: Dosing accuracy of two insulin pre-filled pens.

PMID- 18620631
TI  - [Happy Audit study. Management of a project on respiratory infection financed by
      the European community].

PMID- 18620632
TI  - [On prescription of physical exercise].

PMID- 18620633
TI  - [Measurement of the evaluative capacity of the CVP-35 questionnaire for
      perceiving the quality of professional life].
AB  - OBJECTIVE: To establish the CVP-35 evaluative properties to measure the
      professional quality of life (PQL). DESIGN: Prospective, observational study.
      SETTING: A primary care area in the Community of Madrid, Spain. PARTICIPANTS: A
      total of 149 sanitary workers with some burnout sign measured by Maslach Burnout
      Inventory (MBI) participated. MEASUREMENTS: They fulfilled MBI, Goldberg Health
      Questionnaire (GHQ-28), and CVP-35 questionnaires at the beginning and after a
      year of follow-up, in which 73 subjects took part in activities for coping
      stress. It was assessed the change of PQL and their domains managerial support
      (PQL-MS), work load (PQL-WL), intrinsic motivation (PQL-IM) for the subjects with
      variations at the MBI, or GHQ-28 punctuation greater than 0.5 SD of the initial
      distribution. RESULTS: Variations in CVP-35 and their domains correlate weakly
      with changes in MBI and GHQ-28 (r<0.500), but they are congruent with the
      conceptual model. In the individuals with significant variations in the GHQ-28,
      they appreciate an average change in PQL and their domains between 0.18 and 0.55
      points (absolute value). In those with significant variations in the MBI domains,
      PQL presented average absolute variations between 0.23 and 0.45 points, PQL-MS
      between 0.30 and 0.67, PQL-WL between 0.01 and 0.55 and PQL-IM between 0.22 and
      0.83 points. CONCLUSIONS: CVP-35 is a sensitive-to-change instrument under
      population point of view. Changes in PQL perception or in any of their domains of
      0.5 points could be pointed as relevant.

PMID- 18620634
TI  - [Commentary: Reassessment of the validity of the QPL-35 questionnaire:
      sensitivity to change and significant changes and minimum significant
      difference].

PMID- 18620635
TI  - [Randomized clinical trial for primary care patients with neck pain: manual
      therapy versus electrical stimulation].
AB  - OBJECTIVE: To compare the effectiveness of manual therapy (MT) versus
      transcutaneous electrical nervous stimulation (TENS) in reducing the intensity of
      pain in patients with subacute or chronic neck pain (NP) attended at primary care
      physiotherapy units (PCPU). DESIGN: Randomised clinical trial. SETTING: Thirteen
      PCPU in 4 health districts of the Community of Madrid, Spain. PARTICIPANTS:
      Ninety patients with subacute or chronic NP attended. Lost after intervention: 3.
      INTERVENTIONS: At random, 47 patients were allocated to MT treatment and 43 to
      TENS. MAIN MEASUREMENTS: Social and demographic characteristics and prognosis
      variables in the intervention groups were measured. Intensity of pain before and
      after intervention was calculated by mean values on the analogue visual scale
      (present moment, average and worst pain of the last 2 weeks). Side-effects were
      also measured. RESULTS: Difference between before-and-after pain was 21.83 mm
      (95% CI, 13.71-29.95) for the group treated with Transcutaneous electrical
      nervous stimulation and 22.87 mm (95% CI, 17.11-28.64) for manual therapy. The
      difference in averages on comparing the 2 procedures for improvement was 1.04
      (95% CI, -8.66% to 10.75%). CONCLUSIONS: TENS and MT significantly reduce
      patients' perceived intensity of pain, although there were no differences between
      the 2 groups.There are no conclusive results for the alternative physiotherapy
      treatments that determine a clear strategy of intervention.

PMID- 18620636
TI  - [Validation of the Life-Support Preferences Questionnaire (LSPQ) for its use in
      Spain].
AB  - OBJECTIVE: To validate the Life-Support Preferences Questionnaire (LSPQ) for its
      use in Spain. DESIGN: Three-stage study: a) translation and linguistic
      adaptation; b) evaluation of its validity; and c) validation of its psychometric
      properties. SETTING: Nine primary care nursing clinics and 2 university classes
      in Granada, Spain. PARTICIPANTS: Patients who were of age and were first- or
      second-year university students, without any cognitive deterioration. MAIN
      MEASUREMENTS: The equivalence of the translation and the original was checked by
      bilingual people; its linguistic and grammatical standard was appraised by
      experts in Spanish. The validity of the questionnaire was evaluated by 15 judges
      experts and 20 patients; linguistic complexity (Szigriszt index); stability in
      time (McNemar test); internal consistency (Cronbach's alpha). RESULTS: a) 2
      bilingual people did a translation that was reviewed by 6 experts in Spanish.
      After alterations suggested by the experts, the bilingual people ratified its
      equivalence with the original; b) 15 experts affirmed that each item was a good
      indicator of care preferences at the end of life; c) 20 users confirmed the
      acceptability and comprehensibility of the questionnaire; d) reliability: 299
      participants out of the 369 initially selected filled in the questionnaire; and
      e) its stability was 0.92; and its internal consistency, 0.85. CONCLUSION: The
      LSPQ questionnaire in Spanish (LSPQ-e) is a reliable tool, designed to help
      patients to clarify their care and treatment preferences at the end of their
      lives.

PMID- 18620637
TI  - [Effects of a structured exercise programme on cardiovascular risk programmes in
      post-menopausal women. CLIDERICA study].
AB  - OBJECTIVE: To analyse the influence of a physical exercise programme of
      strength/stamina on cardiovascular risk factors in low-risk post-menopausal
      women. DESIGN: Six-month randomised clinical trial with post-menopausal women.
      SETTING: Three health centres in the autonomous community of Murcia, Spain.
      PARTICIPANTS: Sixty-three post-menopausal women aged 45 to 59 at low
      cardiovascular risk. INTERVENTIONS AND MAIN MEASUREMENTS: They were split into 2
      groups: a) control: 23 people with no specific intervention, and b) 40 people
      with an intervention of strength/stamina exercise with protocol for in water and
      on land. At their initial and final visits, everyone in the 2 groups had
      anamnesis, physical examination, and general analyses, including Apo A, Apo B,
      insulin, serum creatinine, creatinine clearance, creatinine in urine,
      albuminuria, ultrasensitive PCR, and HOMA index. RESULTS: The insulin levels
      increased in the control group by 2.02 mU/L and dropped in the experimental group
      by 0.13 mU/L (P=.021). At the start of the study, creatinine in the control group
      was 0.83+/-0.12 mg/dL; and at the end, 0.91+/-0.02 mg/dL. In the intervention
      group it was 0.84+/-0.12 mg/dL at the start and 0.90+/-0.13 mg/dL at the end
      (NS). Systolic blood pressure dropped in both groups, with a bigger drop in the
      exercise group (11.81 vs 0.17 mm Hg) (P=.0001). HDL-C values increased in the
      control group by 4.97 mg/dL; and in the experimental group, by 3.46 mg/dL (NS).
      CONCLUSIONS: A controlled programme of strength/stamina physical exercise reduces
      the cardiovascular risk of post-menopausal women.

PMID- 18620639
TI  - [The practice of "being attentive" (mindfulness) in medicine. Impact on patients
      and professionals].

PMID- 18620638
TI  - [What do men between 50 and 70 know about the effectiveness, the benefits, and
      the risks of prostate cancer screening?].
AB  - OBJECTIVE: To evaluate the understanding of the population on prostate cancer
      screening. DESIGN: Descriptive study. SETTING: Primary care teams in the province
      of Barcelona, Spain, from april to september 2005. PARTICIPANTS AND CONTEXT: Men
      between 50 and 70 years old without prostate symptoms and seen in the clinics of
      12 primary care teams. METHOD: Systematic sample. VARIABLES: age, marital status,
      educational level, and self-perceived health status. Appraisal of knowledge
      through a 14-question questionnaire referring to the key ideas, previously
      defined by a group of experts, requisite before deciding on prostate cancer
      screening. RESULTS: N=221. Mean age, 59.9 (SD, 5.9); educational level, primary
      or lower: 63.4%; 89.1% (95% CI, 84.4-92.6) did not have sufficient knowledge
      about prostate cancer screening. In the questions on what PSA is and what it is
      for, over 50% said they did not know; 63.3% recognised that prostate cancer was a
      highly prevalent illness; 84.6% replied that early detection of prostate cancer
      avoids deaths; 49.8% did not know whether the doctor had doubts on this question;
      and 38.9% thought he didn't. There were no differences in knowledge for any of
      the variables studied. CONCLUSIONS: Although prostate cancer screening is widely
      known about, the information of the population is scant and often wrong. Existing
      scientific uncertainty on the use of screening is the aspect that is least known
      by users.

PMID- 18620640
TI  - [What are patients' rights?].

PMID- 18620642
TI  - [Are circular and reflexive techniques useful in clinical interviews with the
      family doctor?].

PMID- 18620641
TI  - [Outbreak of Mediterranean exanthematic fever due to tick bites in a public
      square].

PMID- 18620643
TI  - [The home visit briefcases of family doctors].

PMID- 18620645
TI  - [Brazil has to teach Spain as well].

PMID- 18620644
TI  - [Programme in primary care centres to promote physical activity. Pilot study].

PMID- 18620647
TI  - [Flu vaccination as a cardiovascular preventive measure: widely overlooked].

PMID- 18620649
TI  - [Monoclonal gammopathies of uncertain significance].

PMID- 18620650
TI  - [Self-care behavior and patients' knowledge about self-care predict
      rehospitalization among older adults with heart failure].
AB  - INTRODUCTION: This study examined the association of self-care behavior and
      patients' knowledge about self-care with rehospitalization among older adults
      with heart failure (HF). METHODS: Case-control comparison (116 cases and 209
      controls) nested in a prospective cohort of patients aged 65 years and older
      admitted for HF at 4 Spanish hospitals. Cases were patients experiencing a first
      emergency rehospitalization in the 6 months following the index hospital
      admission. Controls were patients who did not undergo a rehospitalization during
      such time-period. RESULTS: The number of self-care behaviors was inversely
      associated with the frequency of readmission (p for linear trend: 0.006).
      Compared with patients showing the appropriate self-care behavior, hospital
      readmission was more frequent among those who did no go for a walk daily or did
      not engage in any daily physical activity (hazard ratio [HR] 1.55; 95% confidence
      limits [CL] 1.04-2.29), and among those who did not keep their medical
      appointments (HR 1.82; 95% CL 1.10-3.02). Hospital readmission was also more
      frequent among patients who: failed to take their medication at the scheduled
      time (HR 2.07; 95% CL 1.15-3.72); stopped taking their medication when it
      disagreed with them (HR 1.76; 95% CL 1.08-2.85); and failed to adhere to their
      drug treatment (HR 1.96; 95% CL 1.29-2.98). Furthermore, the fewer the number of
      behaviors which patients knew to be required for self-care, the greater the
      frequency of rehospitalization (p for linear trend:0.029). CONCLUSIONS: A lower
      degree of self-care and of patients' knowledge about self-care predicted a higher
      risk of hospital readmission.

PMID- 18620651
TI  - [Poisonings by oral antidiabetic drugs in Spain. Analysis and evolution during 13
      years (1991-2003)].
AB  - INTRODUCTION: The prevalence of diabetes type 2 increases and increased in the
      next years. The pharmacology treatment of the diabetes type 2 is the oral
      antidiabetic oral drugs. The objective of our study is to know the existence and
      evolution of the poisonings by oral antidiabetics in Spain. We have studied the
      poisonings registered by oral antidiabetics in the National System of information
      toxicological, centre of national reference for acute poisonings in our country,
      during period 1991-2003. RESULTS: The total number of poisonings was of 309
      subjects, being more frequent in women 52.9% versus 47.1% in men. The clinical
      poisonings were classified in asymptomatic 13.9%, low symptoms 49.5% moderate
      serious 31.3% serious 5.1%. The pharmacologic group with greater number of
      poisonings was of sulfonilurea 66.5%, within this group the glyburide one. In the
      last years poisonings with but of a drug appear appearing in the 2002 poisoning
      by triple therapy (sulfonilurea-metformin and alpha-glucosidase inhibitor). It is
      important to emphasize the absence of mortality and the modification of
      prescription increase of cases of metformin and diminution of alpha-glucosidase
      inhibitor. In our study we emphasized the greater one I number of poisonings in
      group of suckling babies and children with respect to the adults. Everything
      shows the importance of the correct prescription and use of the oral
      antidiabetics.

PMID- 18620652
TI  - Analysis of 27,248 hospital discharges for heart failure: a study of an
      administrative database 1998-2002.
AB  - AIMS: To describe the epidemiology of hospital admissions for heart failure in 32
      hospitals. To define the profile of those attended by Internal Medicine (IM).
      METHODS AND RESULTS: Analysis of the Minimum-Basic-Data-Set registry of 32 public
      Spanish hospitals, during 1998-2002, identifying those cases whose main or
      secondary diagnosis was heart failure, with attention to age, sex, length of
      stay, season, outcome, number of diagnoses, Diagnostic Related Groups (DRG), and
      coded procedures. There were 2,787,008 discharges, 27,248 with heart failure
      (15,737 IM, 7,735 Cardiology and 3,776 other services). Discharges for heart
      failure increase from 1998 to 2002 (r(2) = 0.7232). Of the total, 44% were men
      (average age 70.98 years; 95% CI 70.08-70.47) and 56% were women (74.77 years;
      95% CI 74.61-74.93; p < 0.0001). The global in-hospital mortality rate was 11.1%
      and we found differences between Cardiology and MI. MI patients were older (74
      years compared to 69, p < 0.0001), had greater comorbidity, a similar length of
      stay (11.1 days), and a lower number of coded diagnostic procedures. Associated
      pathologies were different. Seasonal variation is clear. CONCLUSION: The
      incidence of discharges for heart failure is high and steadily increasing,
      although this is more evident in IM. The populations attended by the two services
      are different, which makes it difficult to ascertain differences in handling. The
      results are slightly different from those reported in other countries.

PMID- 18620653
TI  - [A series of 618 cases of monoclonal gammopathies of undetermined significance:
      predictive factors of disappearance of monoclonal component or evolution to
      malignant gammopathies].
AB  - INTRODUCTION: How to identify monoclonal gammopathies of undeterminated
      significance (MGUS) at risk for progression has been studied for the last years.
      AIMS: To study the incidence of MGUS in a region with 300,000 inhabitants and
      factors which associate with a) monoclonal gammopathy disappearance (transient
      MGUS) b) evolution to malignant gammopathy. METHODS: Study of 618 MGUS. RESULTS:
      Incidence: 30/40 new cases a year with increase to 70 cases a years in the latest
      years of study. Age and gender: 71,4 y (32-100), male/female ratio 1.4.
      Associated pathology: infection 328, heart diseases 249, rheumatic diseases 211,
      liver diseases 108, cancer 80, neuropathy 43. Monoclonal proteins: IgG 407, IgM
      78, IgD 2, biclonal 16, triclonal 1; no heavy chain 21, light chain Kappa 389.
      Variables (mean): monoclonal component: 14 g/l, ESR 32,5, bone marrow: 5,9%
      plasma cells beta2-microglobulin: 2,59 mg/l, albumin: 3,1g/l, bone survey: normal
      39,5%. Evolution: transient MGUS 20 cases. Time to disappearance 2,6 months (1,4
      4,6). Evolution to malignant gammopathy 24 cases, time to progression 3 years (IC
      1,82-4,3). RESULTS: Several factors were associatedc with malignant
      transformation: heavy chain IgA (p < 0,002), ESR (p < 0,001), age < 70 (p <
      0,05), bone marrow percentage of plasma cells (p < 0,002) y ostheoporosis (p <
      0,005). A MGUS follow up model is suggested.

PMID- 18620654
TI  - [The Strategic Plan for the development of Internal Medicine in Andalusia].
AB  - The Strategic Plan for the Development of Internal Medicine in Andalusia arose
      from the need that the internal medicine doctors had to redefine the purpose and
      values of their specialty to cope with the numerous changes occurring in the
      health care area. The project was developed in three phases. First, the tendency
      of the health care system and current position of the specialty were analyzed.
      After, the internal and external opinions on the present-future of Internal
      Medicine were checked out. Finally, five strategic lines with their action plans
      were established. Specific objectives were defined within each line: results to
      be achieved, methodology according to action plan. After several years of
      collegial work in this initiative, very positive results have been achieved. We
      conclude that the Strategic Plan has been useful to better define the position of
      our specialty and to state which tools such as those mentioned are effective to
      cope with the new challenges that may occur in other groups.

PMID- 18620655
TI  - [Current state of adjuvant treatment to surgery in the initial stages of nonsmall
      cell lung cancer].
AB  - The results of the recently performed randomised trials support the conclusion
      that adjuvant chemotherapy confers survival advantage in early stage in non-small
      cell lung cancer, and now has become the standard of care for patients with
      resected stage II and IIIA. The role of adjuvant chemotherapy for stage I disease
      remains controversial. Only some patients benefit from systemic adjuvant therapy
      and we need to identify factors of patients most likely to respond to
      chemotherapy. The purpose of this article is to provide a general overview of
      adjuvant chemotherapy for early stage in non-small cell lung cancer.

PMID- 18620656
TI  - [Oral papillomatosis].

PMID- 18620657
TI  - [Broken heart].

PMID- 18620658
TI  - [Cerebral vascular accident in patient with systemic lupus erythematosus and
      antiphospholipid syndrome].

PMID- 18620659
TI  - [Brain abscess due to pulmonary arteriovenous malformation].

PMID- 18620660
TI  - [Fever and crusty skin lesions after local traumatism].

PMID- 18620661
TI  - [Health care quality and safety in the clinical governance].

PMID- 18620663
TI  - [All and part. Informed consent forms and clinical information procedure].

PMID- 18620664
TI  - [Patient safety and management of risks. Reply].

PMID- 18620665
TI  - [Wallemberg's syndrome in patient without vascular risk factors].

PMID- 18620666
TI  - [Onset of disseminated tuberculosis resembling a neoplasm].

PMID- 18620667
TI  - [Biliary ileus as a consequence of a cholecystoduodenal fistula (Bouveret
      syndrome)].

PMID- 18620668
TI  - [Respiratory syncytial virus infections. Old challenges and new strategies].

PMID- 18620670
TI  - [Thrombocytosis in the oncology-haematology clinic: description, aetiological
      diagnosis and progression thrombocytosis].
AB  - INTRODUCTION: Thrombocytosis is a common cause of patient referral to a
      paediatric haematologist specialist which requires a significant number of
      laboratory tests and visits to confirm the diagnosis. The aim of our study has
      been to analyse the characteristics of patients referred to our centre for
      specialised thrombocytosis assessment. Based on this assessment we established
      the criteria patients must fulfil to be recommend for further hospital study.
      PATIENTS AND METHODS: We categorised the 33 patients referred for thrombocytosis
      assessment according to sex, age, origin, personal and family history, platelet
      count at diagnosis and the reason why the red and white blood count at diagnosis
      (Haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin, leukocyte,
      neutrophils, lymphocyte and monocyte count), maximum platelet count during follow
      up and other complementary examinations were done. The final diagnosis itself and
      number of previous visits before were also considered. The classification used to
      grade thrombocytosis was: low (500-700 X 10(3)/microl), mild (700-900 x
      10(3)/microl), severe (900-1.000 x 10(3)/microl) and extreme (> 1.000 x
      10(3)/microl). RESULTS: There was no predominance of males or females. 45 % of
      patients were under 2 years old and 55 % of them came from their primary care
      centre. The mean platelet count at the first medical visit was 669,000 (mild
      thrombocytosis). During follow-up, 24 % of the patients reached extreme platelets
      levels. In 28 % the initial blood count was performed because of an infection.
      The most frequently requested laboratory test was iron metabolism (82 % of the
      cases). All cases correspond to secondary thrombocytosis (48 % were reactive to
      infections, 24 % secondary to iron deficiency, and 15 % were associated to both
      causes). The mean number of visits before hospital discharge was 5.12.
      CONCLUSIONS: The finding of thrombocytosis in the majority of the cases studied
      was casual or in the context of an infectious process. Most of the thrombocytosis
      were mild. Due to the extremely low incidence of primary thrombocytosis in
      childhood and the fact that diagnosis is made by exclusion of other
      possibilities, the initial study of these patients should be done in primary care
      centres. The first conditions to be ruled out are infectious, inflammatory or
      bleeding processes. Once these causes are excluded, the most useful complementary
      test is to measure iron level given the relation between iron deficiency and
      thrombocytosis. Once these causes are ruled out and thrombocytosis persists, it
      would then be indicated to refer the patient to a paediatric oncology-haematology
      department for a more exhaustive follow-up.

PMID- 18620669
TI  - [Severe acquired aplastic anemia: historical outcome of patients treated by
      allogeneic bone marrow transplantation from matched sibling donors. A study by
      the Spanish Group for Bone Marrow Transplantation in Children (GETMON)].
AB  - INTRODUCTION: Allogeneic haematopoietic stem-cell transplantation is the
      treatment of choice for acquired aplastic anaemia in children. Experience with
      this approach from Spanish Working Party for Bone Marrow Transplantation in
      Children in two sequential time periods (1982-1990 and 1991-2004) is reported.
      PATIENTS AND METHODS: Sixty two consecutive patients with a median age of 10
      years were transplanted; 18 in the 1982-1990 period and 44 in the 1991-2004
      period. Conditioning regimen consisted mainly of irradiation and cyclophosphamide
      in the first period (72 % of patients) and cyclophosphamide +/- anti-thymocyte
      globulin (62 %) in the second. Graft versus host disease prophylaxis consisted of
      cyclosporine in most patients (57/62). RESULTS: Fifty one patients are alive and
      disease-free at a median follow-up of 127 months. Five years probability of event
      free survival is 82 %. The survival increased from 61 % to 91 % during the two
      time periods. Eleven patients died from graft failure or rejection (3), acute or
      chronic graft versus host disease and infection (4) or multi-organ failure (4).
      Univariate analysis identified two significant prognostic factors: interval
      diagnostic/transplant and time period of transplant (for both p = 0.03).
      CONCLUSIONS: This experience corroborates that allogeneic haematopoietic stem
      cell transplantation is the best treatment for severe acquired aplastic anaemia,
      with a current disease-free survival of 90 % of patients.

PMID- 18620671
TI  - [Primary cardiac tumours in infancy].
AB  - INTRODUCTION: Primary cardiac tumours are very rare in the paediatric age, their
      incidence varies from 0.0017 % to 0.28 %. More than 90 % are benign in nature.
      The most common variety is the rhabdomyoma, present in over 60 % of cases with
      tuberous sclerosis. MATERIAL AND METHODS: We performed a retrospective analysis
      of medical records with a diagnosis of primary cardiac tumor between March 1977
      and March 2007, finding a total of 27 patients. RESULTS: The age of initial
      diagnosis is more prevalent in the neonatal period, beginning with the discovery
      of a heart murmur (11 cases). There was no difference in gender distribution. In
      14 patients were found cardiomegaly on chest radiograph. According to the
      echocardiography characteristics there were diagnosed 20 rhabdomyomas, 2
      fibromas, 2 pericardial teratomas and 3 non classifiable tumours. Most were
      located in the left ventricle. Echocardiography, cardiac catheterization was also
      performed in 3 cases and angioresonance in 5 cases. During their evolution,
      episodes of arrhythmias were observed in 11 patients, 5 patients required some
      sort of surgical procedure, which confirmed the histopathology diagnosis. In 3
      patients the initial cause of death was cardiological. The 75 % of cases with
      rhabdomyomas presented or developed tuberous sclerosis. In most of the
      rhabdomyomas (13 cases), there was a spontaneous regression. CONCLUSIONS:
      Firstly, there is shown to be a low prevalence of this disorder in children.
      Rhabdomyoma is the most common primary cardiac tumour in our study and it was
      associated in 75 % of cases with tuberous sclerosis. The diagnosis is more common
      in the early neonatal period after auscultation of a cardiac murmur and
      echocardiography, the diagnostic technique of choice, other imaging techniques,
      such as angioMRI not being of much for diagnosis in children. The emergence of
      foetal echocardiography allows early detection. The course is benign in most
      tumours, rhabdomyomas tending to regress spontaneously. It must be monitored as
      the occurrence of arrhythmias during its evolution will require medical
      treatment. Surgery is needed in cases with severe symptoms, due to obstruction in
      the ventricular output tracts. One option is the surgical cardiac transplant in
      non-resectable life-threatening tumours.

PMID- 18620672
TI  - [Incidence and clinical characteristics of congenital heart disease in Badajoz
      Province, Spain].
AB  - INTRODUCTION: There is no clear consensus as regards the exact incidence of
      congenital heart disease. The objective of this study was to determine the
      incidence of congenital heart defects in Badajoz province (Spain). MATERIAL AND
      METHODS: This is a retrospective study based on the clinical histories of 742
      patients who were seen for the first time during 1997 in the paediatric
      cardiology unit of Badajoz Women and Children's Hospital. The incidence of
      congenital Heart defects is calculated by adding the number of patients assessed
      in 1997 and those who will be assessed in the future, considering the population
      born in 1997. The last figure is inferred from the number of patients who were
      born before 1997 and were assessed in that year, comparing the number of newborns
      between 1997 and previous years. The number of patients is divided by the total
      newborns in 1997 and multiplied by 1,000. RESULTS: Congenital heart defects were
      found in 15.6 % of the patients seen during 1997. The incidence ranges from 16.1
      to 5.4 new cardiac diseases per 1,000 newborn babies per year if some minor
      congenital heart defects that are not considered in other publications are
      excluded, such as interatrial communication of the ostium secundum type,
      interventricular communication of the small muscle, mild prolapsed mitral valve,
      bicuspid aortic valve, patent ductus arteriosus in prematures infants, silent
      ductus arteriosus and congenital arrhythmias. CONCLUSIONS: The incidence of
      congenital heart defects in Badajoz province range from 16.1 to 5.5 new cardiac
      diseases per 1,000 newborn babies per year. We consider that the incidence in the
      Badajoz province is reliable and similar to other recent publications.

PMID- 18620673
TI  - [Care of the critically ill child with heart disease in Spain].
AB  - INTRODUCTION: The objective of the present study is to present the organization
      of the resources of paediatric cardiac critical care in Spain. PATIENTS AND
      METHODS: Data were collected through questionnaires sent by e-mail to Spanish
      PICUs. RESULTS: 22 PICUs were enrolled. The median number of beds were 9.5 (4-18
      beds). Total cardiac admissions represented a 20 % of total PICUs admissions per
      year, firstly for congenital heart defects, and secondly for respiratory
      problems. Cardiac surgical activities were carried out in 16 centres, centralized
      in PICU in 10 cases. Mechanical support of the myocardium was performed in 7
      PICUs. A total of 10 participating PICUs considered echocardiograph training
      necessary and also an increase in the amount of activity for better results.
      CONCLUSIONS: Paediatric cardiac critical care involves a significant use of
      resources, including PICUs with no surgical activity. This study is useful for
      detecting common problems and for improving clinical care.

PMID- 18620674
TI  - [Nosocomial infections in pediatric patients following cardiac surgery].
AB  - INTRODUCTION: Nosocomial infection (NI) is a possible complication in patients
      who undergo cardiac surgery, and represents an important cause of morbidity and
      mortality. This study was undertaken to determine the NI rate, main risk factors,
      and microbial spectrum in a paediatric intensive care unit (PICU) for this group
      of patients. PATIENTS AND METHODS: A prospective review was performed, including
      all patients admitted to the PICU after cardiac surgery between December 2003 and
      November 2004. NI was defined according to Centers for Disease Control criteria.
      RESULTS: Sixty-nine patients were included. Sixteen patients (23.2 %) acquired at
      least one episode of NI. The NI rate was 4.9 per 100 patient-days. The most
      common NI was pneumonia, followed by urinary tract infection. There were no
      episodes of sepsis. No patients died from infectious causes. The main
      aetiological organism was Haemophilus influenzae, associated with 41.6 % of
      pneumonias, and followed by Pseudomonas aeruginosa. No multiresistant organisms
      were isolated. There was a statistically significant association between the
      duration of use of external devices (mechanical ventilation, urinary and central
      venous catheterization) and development of NI. CONCLUSIONS: Aggressive monitoring
      and support devices are the main risk factors for NI. Based on our data, we
      suggest early removal of these. Presumed NI should be diagnosed according
      standard criteria before starting antibiotic therapy, and treatment modified
      depending on culture results.

PMID- 18620675
TI  - [Quality control of nosocomial infection in PICU].
AB  - INTRODUCTION: Nosocomial infection represents a problem of public health given
      his high morbidity and mortality, and the cost that it causes to the sanitary
      system. OBJECTIVE: To analyze the nosocomial infection related to the principal
      invasive techniques realized in the paediatric intensive care unit of our
      hospital. MATERIAL AND METHODS: We prospectively analyzed the epidemiological
      information (days of hospitalization, days of placement of devices, intravascular
      and closed drainage system, and mechanical ventilation) and the incidence of
      nosocomial infections (bacteriemias, pneumonias, urinary tract infections) in the
      patients admitted during the years 2000-2004. RESULTS: There was analyzed a total
      of 302 patients finding an accumulated incidence of nosocomial infection of 9.76
      %. The microorganisms isolated with major frequency were the gramnegative stain
      (46.60 %), followed by Candida sp. (33.30 %) and grampositive cocci (20.01 %).
      The predominant location of infection was the bacteriemia, with an incidence of
      4.09 % (2.99 % of primary bacteraemia Vs 1.10 % of catheter related infection).
      The mean rate of incidence of bacteriemias associated to intravasculares devices
      (BADV) was 8.92 (NNISS 7.3 ) with mean rate of utilization of the device of 0.65
      (> Pc90 of the NNISS). The pneumonia associated with mechanical ventilation
      (NAVM) presented a mean rate of incidence of 1.80 departing from a mean rate of
      utilization of 0.27 (< Pc25 of the NNISS). The urinary infection associated with
      the closed drainage system presented an average rate of effect of 2.63 , with a
      mean rate of utilization of the closed drainage system of 0.37 (Pc75).
      CONCLUSIONS: Nosocomial infection represents an important problem in PICU. These
      data allow us the knowledge of the incidence of nosocomial infection in our PICU
      and target the strategies for reducing morbidity and mortality.

PMID- 18620676
TI  - [Hemophagocytic syndrome secondary to visceral leishmaniasis].
AB  - Haemophagocytic syndrome is a disease diagnosed according to clinical and
      analytical criteria, related to many infectious diseases. It is exceptionally
      described in patients infected with Leishmania. Visceral leishmaniasis is an
      uncommon disease in our country except in some areas where it is endemic. Its
      diagnosis is sometimes difficult and the use of other methods currently available
      is needed. Haemophagocytic syndrome treatment is based on established
      chemotherapy protocols, but when it is secondary to Visceral Leishmaniasis, it
      may be an exception, since the abnormalities can be resolved by treatment of the
      infection itself. This treatment has improved recently as Liposomal Amphotericin
      B has replaced classic antimonials, being more beneficial due to less adverse
      effects and a shorter treatment time.

PMID- 18620677
TI  - [Poland syndrome: description of two patients in the same family].
AB  - Poland syndrome is a congenital condition that consists of the unilateral absence
      of the large pectoral muscle, ipsilateral sympbrachydactyly, and is occasionally
      associated with other malformations of the anterior chest wall and breast. The
      aetiology of Poland's syndrome is unknown, although it is believed to be caused
      by an interruption or reduction in the embryonic circulation during pregnancy,
      and the majority of reported cases are sporadic. Only in a few instances there is
      a familial incidence. We describe the occurrence of Poland's syndrome in two
      cousins and the malformation is mainly in the large pectoral muscle.

PMID- 18620678
TI  - [Complete vascular rings].
AB  - The complete vascular rings, embryological anomalies of the aortic arch and great
      vessels, are frequently incidental findings, although patients with significant
      anomalies can present with upper airway and oesophagus compression, resulting in
      non-cardiac morbidity. The diagnostic needs high clinical suspicion. We describe
      six cases, with a mean age of two and a half months at diagnosis. The objective
      of our review is to describe the type of complete vascular ring (double aortic
      arch, right circumflex aortic arch and right aortic arch with aberrant left
      subclavian artery and left ligamentum arteriosus), the most common symptoms
      (respiratory symptoms including constant high-pitched, aggravated crying) and
      invasive and non-invasive diagnostic procedures (esophagograms, CT, MRI).

PMID- 18620679
TI  - [Hereditary juvenile cobalamin deficiency due to mutations in GIF gene].
AB  - Inborn errors of cobalamin (Cbl) metabolism affect its absorption, transport, as
      well as its intracellular metabolism. Hereditary juvenile megaloblastic anaemia
      due to cobalamin deficiency, results from defects in Cbl absorption. There is a
      lack of vitamin B12 in congenital pernicious anaemia due to intrinsic factor
      deficiency and megaloblastic anaemia 1 due to selective intestinal malabsorption
      of vitamin B12 or Imerslund-Grasbeck syndrome. Differential diagnosis can't be
      accomplished only by clinical and biochemical findings. We present a patient from
      Spain with a megaloblastic anaemia due to intrinsic factor deficiency (IFD). The
      patient is a compound heterozygous in GIF gene for a splice site mutation
      inherited from his mother and a missense change inherited from his father. The
      identification of disease-causing mutations in specific genes has improved our
      ability to diagnose many of these conditions.

PMID- 18620680
TI  - [Pneumococcal conjugate vaccine failure in HIV-infected child. Clinical case].
AB  - Despite appropriate antimicrobial therapy and vaccination, invasive pneumococcal
      infections remain associated with significant mortality, especially in selected
      high-risk groups (asplenic, humoral immunity deficient patients, etc.). We
      present a 13-year-old caucasian boy with HIV infection (vertical transmission).
      He received treatment with highly-active antiretroviral therapy (amprenavir,
      lamivudine and zidovudine) and vaccination with 23-valent vaccine (6 years old)
      and 7-valent pneumococcal conjugate vaccine (10 years old). His CD4 count and his
      viral load at these times were 2,063/microl and 13461 cop/ml, when he was 6 years
      old and 1,315/microl and 32400 cop/ml when he was 10 years old, respectively. The
      latest CD4 count (1,000/microl) and his viral load (3800 cop/ml) confirmed
      satisfactory control of the disease. He was referred to our emergency department
      presenting with fever, head and stomach-ache and vomiting. In the following hours
      his condition continued to deteriorate and depressed level of consciousness and
      meningismus were observed. Streptococcus pneumoniae, serotype 18 C, was detected
      in blood and cerebrospinal fluid cultures. Despite appropriate treatment with
      antibiotics (cefotaxime and vancomycin) and anti-oedema medications, brain-death
      was confirmed 24 hours after his admittance.

PMID- 18620681
TI  - [Spanish multidisciplinary consensus on the prevention of respiratory syncytial
      virus infection in children].
AB  - BACKGROUND: A certain degree of feasibility exists in Spanish clinical practice
      with respect to interventions performed to prevent paediatric respiratory
      infection by RSV, including hygienic measures and intramuscular immunoprophylaxis
      with palivizumab. This task involves different paediatric specialties that may
      have a different perception of the magnitude of the problem and different
      professional criteria regarding the most appropriate actions. OBJECTIVES: To
      develop Spanish multidisciplinary consensus on preventing infection by RSV with
      the participation of the paediatric scientific societies involved (SNS, SSPC,
      SSPP and SSHPO). METHODS: Delphi Consensus modified in two rounds was used. The
      study was conducted in four phases: 1) constitution of a multidisciplinary
      Scientific Committee at the recommendation of the scientific entities
      participating in the study, for bibliographic review and submission of the
      recommendations to discussion; 2) constitution of an Expert Panel with 77
      speciality representatives; 3) postal survey organised in two rounds and
      intermediate processing of opinions and issuing of a report for the panellists,
      and 4) discussion of the results in a meeting of the Scientific Committee.
      RESULTS: Consensus was reached on 48 of the 57 preventive recommendations
      analysed. With respect to the 9 remaining issues, no consensus was reached, due
      to differences in professional opinion and the absence of established criteria
      among the majority of the experts. Only in 3 recommendations was the opinion of
      the experts associated with the speciality of origin. CONCLUSIONS: A list of anti
      RSV prophylactic recommendations was submitted, rated in accordance with the
      degree of professional consensus on which they were based. These can be
      considered valid until such time as new scientific information emerges that
      warrants a review thereof.

PMID- 18620682
TI  - [School meals: state of the art and recommendations].
AB  - School meals contribute substantially to overall energy and nutrient intake
      adequacy of children, but also play an important role in the development of child
      food habits and the socialisation process. Evidence shows that school based
      environmental actions, which include changes in school meals and school food
      policies related to increased availability and access to healthy foods and drinks
      while in the school are effective to foster healthy eating practices among
      children. A growing number of children engage in school meals. Available
      information to date shows that the quality of the food on offer is not always
      consistent with dietary guidelines. Vegetables and fish are served less often
      than desirable and excess added fats are used in food preparations. Norms and
      regulations are very detailed regarding food safety issues and administrative
      management of the service, including subcontracting of catering providers and
      care staff. Nutrition and health promotion issues should also be included in
      regulations by means of nutrition recommendations for school meals along with
      information on food based dietary guidelines and portion sizes. School meals
      should be part of the educational project using a whole school approach.

PMID- 18620683
TI  - [Rotavirus and its indirect costs].

PMID- 18620684
TI  - [Bruck syndrome: osteogenesis imperfecta with congenital joint contractures].

PMID- 18620685
TI  - [Isolated vaginal bleeding in three pre-puberty children].

PMID- 18620686
TI  - [Extraordinarily early menarche as an initial sign of central idiopathic
      precocious puberty in a 15 month old child].

PMID- 18620687
TI  - [Cyanotic sobbing spasms in a newborn: an unusual presentation].

PMID- 18620688
TI  - [Bilateral ureteral hydronephrosis secondary to prenatally diagnosed
      hydromucocolpos].

PMID- 18620689
TI  - [Macroamylasemia in paediatrics].

PMID- 18620690
TI  - [Celso's kerion induced erythema nodosum].

PMID- 18620691
TI  - [An adolescent with hyperthyroidism secondary to Hashimoto thyroiditis diagnosed
      in the hyperthyroid phase. Diagnostic difficulties].

PMID- 18620692
TI  - [Upper limb thrombosis in a neonate homozygote for the C677T mutation].

PMID- 18620699
TI  - The association of host and phage DNA with the membrane of Escherichia coli.
AB  - The attachment of DNA to membrane in T4-infected cells was investigated by means
      of the Mg2+-sarkosyl crystals technique. Both parental and progeny phage DNA are
      associated with cell membrane throughout the eclipse period and are subsequently
      detached during the synthesis of mature phage. The initial attachment process
      does not require protein synthesis. Detachment appears to be due to a "late
      function" since it does not occur following infection with a DO mutant (amN82) or
      after treatment with chloramphenicol or tetracycline added 9 min after infection.
      Host DNA remains attached to membrane during the initial stages of infection and
      neither superinfection nor the addition of chloramphenicol alters this
      association.

PMID- 18620700
TI  - Intracellular appearance and some morphological features of viruslike particles
      in an ascomycete fungus.

PMID- 18620701
TI  - Bilateral retiform Sertoli-Leydig cell tumour in a bitch. Alpha-inhibin and
      epithelial membrane antigen as useful tools for differential diagnosis.
AB  - Sertoli-Leydig cell tumours with a retiform pattern similar to the pattern of the
      rete testis are a subtype of sex cord-stromal tumours recognized in the human WHO
      histological classification of ovarian tumours but not in the equivalent
      classification for domestic animals. The morphology of the tumour may be confused
      with that of the more common ovarian epithelial tumours. The gross, microscopical
      and immunohistochemical features of a canine retiform Sertoli-Leydig cell tumour
      and its comparison with the human counterpart are presented in this report. Both
      ovaries were enlarged and cystic. Microscopically, the tumour was cystic with
      tubulopapillary growth characterized by narrow, elongated branching tubules.
      Immunohistochemically, the tumour cells expressed alpha-inhibin, while epithelial
      membrane antigen was not detected, indicating a sex cord-stromal origin of the
      tumour. Additionally, the tumour cells expressed cytokeratin and vimentin in
      addition to oestrogen receptor alpha and progesterone receptor.

PMID- 18620702
TI  - Arteriovenous haemangioma in two dogs and a cat.
AB  - Haemangiomas are benign vascular tumours and several types can be distinguished
      based on microscopical features. Capillary and cavernous haemangiomas are most
      commonly reported in man and domestic animals. Arteriovenous haemangiomas are
      rare variants in man and herein we describe this subtype in two dogs and one cat.
      One dog and the cat presented with a cutaneous vascular lesion, the other dog
      with a bleeding mass in the tongue. Surgically excised masses comprised non
      encapsulated proliferations of variably sized arterial- and venous-like vessels,
      accompanied by clusters of capillaries and immature vascular structures in the
      feline cutaneous tumour and the canine lingual neoplasm. All vasoformative
      elements had von Willebrand factor-positive endothelia enclosed by a smooth
      muscle actin-positive tunica media or by pericytes. The results of this study
      expand the range of differential diagnoses for vascular neoplasms in the dog and
      cat.

PMID- 18620703
TI  - Epithelial distribution and replication of foot-and-mouth disease virus RNA in
      infected pigs.
AB  - Although the pathogenesis of foot-and-mouth disease (FMD) has been extensively
      investigated, relatively few studies have addressed the localization of FMD virus
      (FMDV) and in particular its replication in relation to the typical in-vivo sites
      of FMD lesions. In the present study, pigs were infected experimentally with FMDV
      serotype O UKG 34/2001 and tissue samples were collected from 1 to 4 days post
      infection. Samples were stored at -70 degrees C and frozen sections were prepared
      for in-situ hybridization (ISH). A digoxigenin-labelled RNA probe complementary
      to a coding part of the RNA-dependent RNA polymerase (3D) genomic region was
      prepared. The FMDV positive strand RNA was prominent in the basal layers of the
      epithelium. A diffuse positive signal was also noted in the cytoplasm of cells of
      the stratum spinosum of lesional epithelium, but there was no signal in the
      stratum corneum. Detection of FMDV negative strand RNA was observed in basal
      cells above the basement membrane and along the dermal papillae. The basal cells
      therefore demonstrate the highest signal for detection of the FMDV positive and
      negative strand RNAs in both tongue and foot epithelium. These novel results
      suggest that the epithelial basal cells could be an early replication site of
      FMDV in vivo.

PMID- 18620704
TI  - A simple measure to control for variations in chest electrodes placement in
      serial electrocardiogram recordings.
AB  - Variations in chest electrodes placement in the 12-lead electrocardiogram (ECG)
      are a major concern in interpretation of serial ECG changes, especially those
      changes involving V1 and V2 leads. Documentation of chest electrodes placement
      will help in controlling for these variations by facilitating comparison of
      electrodes placement between serial ECG recordings. This can be achieved by
      recording the distance from suprasternal notch (N) to the position of V1-V2 (V),
      referred to as the NV measurement and is proposed in this brief communication.
      When performed after placement of the electrodes, the NV measurement does not in
      any way interfere with the recommended standardized electrode placement
      procedure. Combining the proposed NV measurement with the numeric measures of V4
      and V6 transverse positions using previously proposed procedures is expected to
      further reduce errors in interpretation of serial ECG recordings.

PMID- 18620705
TI  - Architectures and functional coverage of protein-protein interfaces.
AB  - The diverse range of cellular functions is performed by a limited number of
      protein folds existing in nature. One may similarly expect that cellular
      functional diversity would be covered by a limited number of protein-protein
      interface architectures. Here, we present 8205 interface clusters, each
      representing a unique interface architecture. This data set of protein-protein
      interfaces is analyzed and compared with older data sets. We observe that the
      number of both biological and crystal interfaces increases significantly compared
      to the number of Protein Data Bank entries. Furthermore, we find that the number
      of distinct interface architectures grows at a much faster rate than the number
      of folds and is yet to level off. We further analyze the growth trend of the
      functional coverage by constructing functional interaction networks from
      interfaces. The functional coverage is also found to steadily increase.
      Interestingly, we also observe that despite the diversity of interface
      architectures, some are more favorable and frequently used, and of particular
      interest, are the ones that are also preferred in single chains.

PMID- 18620707
TI  - A case of intravascular B-cell lymphoma presenting as myelopathy and diagnosed
      post mortem.
AB  - The clinical presentation of intravascular lymphoma (IVL) is generally
      nonspecific and misleading and its course from onset to death is rapid. We report
      a case in a 70-year-old right-handed man who presented after 1 month of numbness
      and progressive paresis in both lower limbs and 20 days of urinary and bowel
      involvement. MRI of the cervical and lumbar spine with contrast failed to show
      signal change in the spinal cord. But brain MRI with contrast showed patchy
      lesions in the subcortical white matter of bilateral centrum semiovale and
      periventricular area. The patient's condition worsened rapidly. He died 3 months
      after the first occurrence of symptoms. Autopsy revealed intravascular large B
      cell lymphoma. Our report indicates that myelopathy can be the initial
      manifestation of this disease. Brain biopsy is indicated when neurological
      deterioration with abnormalities is progressive in cerebral MR imaging and when
      tumor is suspected.

PMID- 18620708
TI  - Important sources of variability in clinical studies of neutralizing antibodies
      against interferon beta.
AB  - Interferon (IFN) beta treatment of relapsing-remitting multiple sclerosis (RRMS)
      stimulates production of neutralizing antibodies (NAbs) in some patients.
      However, clinical data supporting the hypothesis that NAbs to IFN beta adversely
      affect patient outcomes are not consistent across multiple studies or different
      forms of IFN beta. Only the PRISMS trial has produced data showing a negative
      impact of NAbs to IFN beta-1a (Rebif) across multiple study endpoints. No such
      data are available for IFN beta-1b (Betaseron) despite completion of a large
      registry study. Biological factors affecting the development of NAbs to IFN beta
      include protein structure, product formulation, administration frequency and/or
      dosing, and patients' immunological responses. Technical factors affecting
      interpretation of clinical trial data on NAbs include inadequate randomization;
      differences in the methods used to measure NAbs and in definitions of NAb
      positivity; selection of NAb-positive patient subpopulations according to titer
      and duration of NAb response; lack of power to detect differences in patient
      subgroups; and different trial durations. Given the complexity of NAb studies, it
      is not possible to generalize from current data regarding the potential impact of
      NAbs on the clinical efficacy of all IFN beta therapies. Differences between IFN
      beta products and their specific trials should be considered when evaluating the
      evidence on this topic.

PMID- 18620706
TI  - Blockade of NF-kappaB using IkappaB alpha dominant-negative mice ameliorates
      cardiac hypertrophy in myotrophin-overexpressed transgenic mice.
AB  - Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor that
      regulates various kinds of genes including inflammatory molecules, macrophage
      infiltration factors, cell adhesion molecules, and so forth, in various disease
      processes including cardiac hypertrophy and heart failure. Previously, we have
      demonstrated that activation of NF-kappaB was required in myotrophin-induced
      cardiac hypertrophy, in spontaneously hypertensive rats, and in dilated
      cardiomyopathy human hearts. Moreover, our recent study using the myotrophin
      overexpressed transgenic mouse (Myo-Tg) model showed that short hairpin RNA
      mediated knockdown of NF-kappaB significantly attenuated cardiac mass associated
      with improved cardiac function. Although it has been shown that NF-kappaB is
      substantially involved in cardiovascular remodeling, it is not clear whether the
      continuous blockade of NF-kappaB is effective in cardiovascular remodeling. To
      address this question, we took a genetic approach using IkappaB alpha triple
      mutant mice (3M) bred with Myo-Tg mice (a progressive hypertrophy/heart failure
      model). The double transgenic mice (Myo-3M) displayed an attenuated cardiac
      hypertrophy (9.8+/-0.62 versus 5.4+/-0.34, p<0.001) and improved cardiac function
      associated with significant inhibition of the NF-kappaB signaling cascade,
      hypertrophy marker gene expression, and inflammatory and macrophage gene
      expression at 24 weeks of age compared to Myo-Tg mice. NF-kappaB-targeted gene
      array profiling displayed several important genes that were significantly
      downregulated in Myo-3M mice compared to Myo-Tg mice. Furthermore, Myo-3M did not
      show any changes of apoptotic gene expression, indicating that significant
      inhibition of NF-kappaB activation reduces further proinflammatory reactions
      without affecting susceptibility to apoptosis. Therefore, development of
      therapeutic strategies targeting NF-kappaB may provide an effective approach to
      prevent adverse cardiac pathophysiological consequences.

PMID- 18620709
TI  - Ataxia and migraine-like headache in a girl with a cerebellar developmental
      venous anomaly.
AB  - Cerebral developmental venous anomalies (DVAs) are generally considered as
      anatomical variants of the venous system without clinical importance. We report
      the case of a 15-year-old girl with recurrent episodes of migraine-like headache
      who presented with subacute vertigo and ataxia associated with intense occipital
      pain. Magnetic resonance imaging (MRI) showed a DVA with signal modifications of
      the surrounding brain parenchyma in the left cerebellar hemisphere. The patient's
      ataxia regressed completely within about 2 months. On a follow-up MRI 4 years
      later the venous malformation and the parenchymal abnormalities were unchanged.
      We attribute the patient's focal neurological dysfunction to regional changes in
      the brain parenchyma, possibly secondary to venous hypertension. Our report
      provides evidence that also uncomplicated DVAs can become symptomatic and
      supports the role of the venous congestion within the DVA territory in
      pathogenesis of some brain parenchymal abnormalities associated with DVAs.

PMID- 18620710
TI  - Levodopa, motor complications and disease progression.

PMID- 18620711
TI  - Survey of PAH in low density residential stormwater ponds in coastal South
      Carolina: false dark mussels (Mytilopsis leucophaeata) as potential biomonitors.
AB  - The distribution of PAHs was studied in sediment and false dark mussels,
      Mytilopsis leucophaeata, of three brackish stormwater retention ponds on Kiawah
      Island, a gated residential community and golf resort. Impervious surface in pond
      watersheds ranged from 5 to 30%. Sediment concentrations were lower than those
      found in other studies of suburban residential areas, and there were no
      significant differences among ponds or seasons. Mean summation PAH16 values for
      sediments in Ponds 67, 100, and 37 were 184.7+/-101.3ng g(-1), 67.5+/-26.0ng g(
      1), and 84.3+/-75.5ng g(-1), respectively. Mussel summation PAH16 concentrations
      from Pond 67 in August (mean 734.5+/-148.1ng g(-1)), and from Pond 37 in December
      (mean 1115.1+/-87.7ng g(-1)), were significantly higher than other ponds. Mean
      summation PAH16 values for mussels in Ponds 67, 100, and, 37 were 555.9+/-219.7ng
      g(-1), 312.5+/-99.1ng g(-1) and 737.8+/-419.8ng g(-1), respectively. The mean
      biota-to-sediment ratio was 7.6+/-8.1. Isomer ratios generally suggested
      pyrogenic sources. False dark mussels are a promising indicator species for PAH
      contamination because they are abundant, easy to sample, bioaccumulate PAH
      profiles representative of the time-integrated sediment profiles, and their PAH
      levels are less variable than either stormwater or sediment samples.

PMID- 18620712
TI  - The effects of acute and repeated oroxylin A treatments on Abeta(25-35)-induced
      memory impairment in mice.
AB  - Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis
      Georgi. The aim of this study was to characterize the effects of oroxylin A on
      the memory impairments and pathological changes induced by Abeta(25-35) peptide
      in mice. The ameliorating effect of oroxylin A on memory impairment was
      investigated using passive avoidance and Y-maze tasks and pathological changes
      were identified by immunostaining and western blotting. Abeta(25-35) peptide
      (5nmol) was administered by intracerebroventricular injection. In the acute
      treatment study, a single dose of oroxylin A (5mg/kg, p.o.) treated 1h before
      behavioral tests was found to significantly reverse Abeta(25-35)-induced
      cognitive impairments based on passive avoidance and Y-maze task findings
      (P<0.05). Moreover, these acute effects of oroxylin A were blocked by diazepam
      (1mg/kg, i.p.), a GABA(A)/benzodiazepine binding site agonist (P<0.05). On the
      other hand, our subchronic studies revealed that oroxylin A (1 or 5mg/kg/day,
      p.o.) for 7 days ameliorated the memory impairment induced by Abeta(25-35)
      peptide. Moreover, Abeta(25-35)-induced increases in GFAP (an astroglia marker)
      and OX-42 (a microglia marker), and increases in iNOS positive cells in the
      hippocampus were found to be attenuated by subchronic oroxylin A (1 or
      5mg/kg/day, i.p., P<0.05). In addition, reductions in the immunoreactivity and
      protein level of ChAT (a cholinergic neuronal cell marker) in the CA3 hippocampal
      area induced by Abeta(25-35) peptide were also attenuated by oroxylin A.
      Furthermore, lipid peroxidation induced by Abeta(25-35) was also reduced by
      oroxylin A. These results suggest that the amelioration of Abeta(25-35) peptide
      induced memory impairment by oroxylin A is mediated via the GABAergic
      neurotransmitter system after a single administration, or by reductions in
      Abeta(25-35) peptide-induced astrocyte and microglia activations, iNOS
      expression, lipid peroxidation, and increased cholinergic neurotransmission after
      subchronic administration.

PMID- 18620713
TI  - Arginine vasopressin V1a receptor antagonist impairs maternal memory in rats.
AB  - Primiparous female rats rapidly respond to foster pups following an extended
      separation from pups after an initial maternal experience. This consolidation of
      maternal behavior has been referred to as maternal memory. The neurochemical
      regulation of maternal memory is not clearly understood. One neuropeptide that
      may mediate maternal memory is arginine vasopressin (AVP), a neuropeptide which
      is modulated around the time of parturition and has an established role in
      learning and memory processes. Thus, the present studies examine the possible
      involvement of AVP in the establishment of maternal memory in female rats.
      Pregnant rats were implanted with chronic cannulae connected to subcutaneous
      osmotic minipumps filled with a V1a receptor antagonist [d(CH2)5Tyr(Me)AVP, 0.1
      12.5 ng/h] or saline vehicle which were chronically infused either into the
      lateral ventricles or bilaterally into the medial amygdala beginning on day 18 of
      gestation. Both the osmotic pumps and the newborn pups were removed 24 h
      following parturition. The effects of the V1a antagonist treatments on social
      recognition and maternal behavior were measured following parturition and
      maternal memory was assessed following a ten day separation from pups. Whereas
      none of the AVP treatments affected the initial establishment of maternal
      behavior postpartum, maternal memory was impaired in rats infused into the
      amygdala with the AVP antagonist (1.25 and 12.5 ng/h). Social recognition was not
      impaired by intracerebroventricular infusion of either the 0.1 or 1.0 ng/h dose
      of the V1a antagonist. The present results suggest a role for medial amygdaloid
      V1a receptors in the establishment of maternal memory.

PMID- 18620714
TI  - Sterols and fatty acids of three harmful algae previously assigned as
      Chattonella.
AB  - Sterol and fatty acid compositions were determined for three harmful algal
      species previously classified in the genus Chattonella (Raphidophyceae): the new
      genus Chloromorum toxicum (ex Chattonella cf. verruculosa), Verrucophora farcimen
      (Dictyochophyceae), previously Chattonella aff. verruculosa, and Verrucophora
      verruculosa (=Pseudochattonella verruculosa) previously Chattonella verruculosa.
      The major fatty acids of C. toxicum were 14:0, 16:0, 18:1n-9, 18:4n-3 and 20:5n
      3, and those of the Verrucophora strains were. 14:0, 16:0, 18:0, 18:4n-3, 18:5n-3
      and 22:6n-3. C. toxicum contained the 24beta-ethyl sterols, poriferasterol and
      clionasterol, as its major sterols. For comparison, the stereochemistry of the 24
      ethyl sterols of two raphidophytes, Chattonella marina and Heterosigma akashiwo,
      was determined to be 24alpha and 24beta, respectively. Both Verrucophora strains
      contained the 27-nor sterol occelasterol as the only detected sterol. This was
      the first time occelasterol has been found in algae.

PMID- 18620715
TI  - Strategies used to increase chlamydia screening in general practice: a
      qualitative study.
AB  - OBJECTIVES: To explore strategies used by chlamydia screening co-ordinators and
      practice staff to implement genital chlamydia screening within general practices.
      METHODS: Qualitative phenomenological study using individual semi-structured
      telephone interviews. Screening co-ordinators were selected purposively in Phase
      1 and 2 areas of the Department of Health National Chlamydia Screening Programme
      in England, where there was significant screening in general practice. Open
      questions were asked about: the factors that determined high chlamydia screening
      rates; maintaining motivation for screening; and strategies to increase screening
      in general practices. RESULTS: Co-ordinators reported that successful screening
      practices had a champion who drove the screening process forward. These practices
      had normalized screening, so all at-risk patients were offered opportunistic
      screening whenever they attended. This was facilitated by a variety of time
      saving methods including computer prompts, test kits in the reception area, youth
      clinics and receptionist involvement. Chlamydia screening was sustained through
      frequent reminders, newsletters containing chlamydia screening rates, and
      advertising to the 'at-risk' population from the screening team. Co-ordinators'
      enthusiasm and project management skills were as important as sexual health
      experience. Co-ordinators reported that to facilitate chlamydia screening across
      all practices, screening could be included in the General Medical Services (GMS)
      contract, and a higher national profile was needed amongst health professionals
      and the public. CONCLUSIONS: All practice staff need to be encouraged to become
      champions of the chlamydia screening programme through education, especially
      aimed at older clinicians and receptionists. The National Health Service should
      consider including chlamydia screening in the GMS contract. Increased public
      awareness will allow screening to be undertaken more quickly and by non-medical
      staff.

PMID- 18620716
TI  - Regional analysis of road mortality in Europe.
AB  - BACKGROUND: Road accidents are the tenth leading cause of premature death
      worldwide and, based on current trends, are likely to become the third leading
      cause of disability-adjusted life years lost by 2020. Road mortality varies in
      time and space both between countries and also between regions within the same
      country. Identifying and understanding the background of regional differences may
      lead to better understanding of the sources of road accidents, and enable the
      application of more effective road safety policies. METHODS: A Bayesian
      ecological regression model based on a unified generalized linear mixed model
      framework is introduced. Population density and country (affiliation) were used
      as covariates and were fitted into the model at the four levels of spatial
      aggregation known as 'nomenclature of statistical territorial units (NUTS)
      regional classification'. RESULTS: Population density has a significant influence
      on road mortality. For all countries together, the elasticity estimate is -0.32,
      meaning that a 10% increase in population density is linked to a 3.2% decrease in
      road fatalities. A multi-level model defined at the NUTS-3 level, taking into
      account the NUTS-2 aggregation, enables infraregional variances in road mortality
      to be taken into account and produces the most reliable estimates of the model
      parameters. Variation in the Bayes relative risk (the mortality ratio
      'standardized' by population density and country effect) is highest at the NUTS-3
      level, but is lower at country level and NUTS-2 level, which suggests that other
      important underlying factors are responsible for the variations in road mortality
      between regions. Mapping the Bayes relative risk enables the identification of
      regions that should be targeted by national and regional policies. Last but not
      least, a new ranking of European countries according to their road mortality
      risk, adjusted for population density, is presented.

PMID- 18620717
TI  - [Dental prosthetic rehabilitation and pre-implant procedure].

PMID- 18620718
TI  - Muscle differentiation in blackspot seabream (Pagellus bogaraveo, Brunnich):
      histochemical and immunohistochemical study of the fibre types.
AB  - The aim of this work was to gain insights into the mechanism of muscle
      differentiation and growth in Pagellus bogaraveo, by studying muscle fibre
      phenotypes identified by immunohistochemistry. At hatching, several layers of
      deep fast-white fibres were covered by a superficial fibre monolayer. At 5 days,
      slow-red fibres appeared near the lateral line nerve. At 40 days, the
      intermediate-pink muscle became visible, and in the slow-red and fast-white
      muscle layers transitions from larval myosin isoforms to the isoforms typical of
      adult muscle occurred. Between 70 and 100 days, small fibres with a distinct
      ATPase profile appeared throughout the fast-white muscle, marking the onset of
      "mosaic" hyperplasia. The myosin of the original superficial monolayer fibres
      underwent two myosin transformations, before being slowly replaced by an adult
      slow-red isoform. In juveniles and adults, the slow-red muscle layer could be
      resolved into two distinct types. The analysis of fibre phenotypes indicated that
      post-larval muscle growth occurred by two distinct stages of hyperplasia. This
      study offers a basis for further comparative and experimental studies with this
      economically relevant species, namely for identifying factors influencing its
      muscle growth dynamics and disclosing underlying mechanisms.

PMID- 18620720
TI  - Effects of four Fusarium toxins (fumonisin B(1), alpha-zearalenol, nivalenol and
      deoxynivalenol) on porcine whole-blood cellular proliferation.
AB  - The in vitro effects of four Fusarium toxins, fumonisin B(1) (FB(1)), alpha
      zearalenol (alpha-ZEA), nivalenol (NIV) and deoxynivalenol (DON), on mitogen
      induced cell proliferation were determined in swine whole-blood cultures.
      Considering the lack of sufficient toxicological data both on single and in
      combination effects, in vitro studies may contribute to risk assessment of these
      toxins. Incubation with increasing concentrations of FB(1) did not produce any
      consequence on proliferation; in contrast alpha-ZEA, NIV and DON showed an
      inhibitory effect. Dose-response curves for each mycotoxin were generated. NIV
      was found to be the most potent toxin followed by DON and alpha-ZEA. The effects
      of both FB(1)+alpha-ZEA and NIV+DON mixtures were also analysed to investigate
      possible interactions. The results indicated that combination of FB(1)+alpha-ZEA
      produces a synergistic inhibition of porcine cell proliferation; whereas there is
      no interaction between DON and NIV on porcine whole-blood proliferation, at
      tested concentrations.

PMID- 18620719
TI  - Increased oxidative stress and antioxidant expression in mouse keratinocytes
      following exposure to paraquat.
AB  - Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to
      induce skin toxicity. This is thought to be due to oxidative stress resulting
      from the generation of cytotoxic reactive oxygen intermediates (ROI) during
      paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes
      which protect against oxidative stress including superoxide dismutase (SOD),
      catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1),
      metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present
      studies we compared paraquat redox cycling in primary cultures of
      undifferentiated and differentiated mouse keratinocytes and determined if this
      was associated with oxidative stress and altered expression of antioxidant
      enzymes. We found that paraquat readily undergoes redox cycling in both
      undifferentiated and differentiated keratinocytes, generating superoxide anion
      and hydrogen peroxide as well as increased protein oxidation which was greater in
      differentiated cells. Paraquat treatment also resulted in increased expression of
      HO-1, Cu,Zn-SOD, catalase, GSTP1, GSTA3 and GSTA4. However, no major differences
      in expression of these enzymes were evident between undifferentiated and
      differentiated cells. In contrast, expression of GSTA1-2 was significantly
      greater in differentiated relative to undifferentiated cells after paraquat
      treatment. No changes in expression of MT-2, Mn-SOD, GPx-1, GSTM1 or the
      microsomal GST's mGST1, mGST2 and mGST3, were observed in response to paraquat.
      These data demonstrate that paraquat induces oxidative stress in keratinocytes
      leading to increased expression of antioxidant genes. These intracellular
      proteins may be important in protecting the skin from paraquat-mediated
      cytotoxicity.

PMID- 18620721
TI  - Prospection, structural analysis and phylogenetic relationships of endogenous
      gamma-phospholipase A(2) inhibitors in Brazilian Bothrops snakes (Viperidae,
      Crotalinae).
AB  - During the last 20 years, there have been an increasing number of reports on
      endogenous phospholipase A(2) inhibitors (PLIs) in the sera of snakes. These
      studies have demonstrated the existence of three different structural classes of
      PLIs (alpha, beta and gamma). The gamma class members are potent inhibitors of
      phospholipases A(2) (PLA(2)) from the venom of Viperidae snakes. These enzymes,
      together with the mammalian pro-inflammatory PLA(2), belong to the IIA class of
      the PLA(2)-superfamily. Although coming from distinct sources, these
      phospholipases A(2) share main structural features. For this reason, gammaPLIs
      have been considered as potential models for the development of selective
      inhibitors of pro-inflammatory PLA(2) in humans. In spite of the rich diversity
      of the ophidian fauna in Brazil, only two gammaPLI representatives, from Crotalus
      durissus terrificus and Lachesis muta, have been described in Brazilian snakes so
      far. Here we investigated the presence of transcripts of novel gammaPLIs in six
      Bothrops species (Viperidae, Crotalinae) commonly found in our country: Bothrops
      alternatus, Bothrops erythromelas, Bothrops jararaca, Bothrops jararacussu,
      Bothrops moojeni and Bothrops neuwiedi. gammaPLI transcripts were present in
      every species analysed. The deduced mature proteins possessed 181 amino acid
      residues following a 19-residue signal peptide, similar to the gammaPLIs from C.
      d. terrificus taken as our model, with the exception of the deduced proteins from
      B. erythromelas and B. neuwiedi snakes. In these particular cases, an insertion
      of 4-amino acid residues was consistently present. A Bayesian tree was obtained
      for the Brazilian Bothrops gammaPLIs, showing four clusters: (1) L. muta and B.
      jararacussu, (2) B. alternatus, (3) B. erythromelas and B. neuwiedi, (4) B.
      jararaca and B. moojeni. Detailed structural analysis and further comparisons of
      these novel Bothrops inhibitors with gammaPLIs from New and Old World snakes are
      provided.

PMID- 18620722
TI  - In vivo influence of cyanobacterial toxins on enzyme activity and gene expression
      of protein phosphatases in Alfalfa (Medicago sativa).
AB  - Irrigation of crop plants with surface water can be a threat if cyanobacterial
      toxins are present in the water. Cyanotoxins are known to cause adverse effects
      in plants. Microcystin (MC), a cyclic heptapeptide, with more than 70 structural
      variants, is a frequently occurring toxin. MC is a specific inhibitor of
      serine/threonine protein phosphatases 1 and 2A (PP1 and 2A), important regulatory
      enzymes in eukaryotic cells. Protein phosphatases consist of a catalytic subunit
      and one or more regulatory subunits. In Alfalfa several isoforms of the catalytic
      subunit of PP1 (MsPP1alpha, MsPP1beta, MsPP1gamma, MsPP1delta, MsPP1varepsilon)
      and PP2A (MsPP2A Calpha/beta/gamma) are known along with isoforms of the
      regulatory subunits of PP2A (MsPP2A Aalpha/beta, MsPP2A Balpha/beta). The in vivo
      effect of environmentally relevant concentrations of cyanobacterial components on
      the mRNA transcript level of the subunits of protein phosphatases 1 and 2A in
      Alfalfa (Medicago sativa) was examined using semi-quantitative RT-PCR. Plants
      were exposed for one week to 5 microg L(-1) microcystin-LR, microcystin-LW,
      okadaic acid and to cell-free cyanobacterial crude extracts from Microcystis
      aeruginosa containing 5 microg L(-1) microcystin-LR and a toxin-free crude
      extract from Synechocystis spp. The protein phosphatase activity in vivo was
      inhibited when exposed to toxins and crude extract containing microcystin-LR, no
      change was induced by Synechocystis crude extract. The gene expression of the
      MsPP1gamma subunit and the MsPP1varepsilon subunit was induced in plants exposed
      to MC-LW.

PMID- 18620723
TI  - An improved automatic time-of-flight picker for medical ultrasound tomography.
AB  - OBJECTIVE AND MOTIVATION: Time-of-flight (TOF) tomography used by a clinical
      ultrasound tomography device can efficiently and reliably produce sound-speed
      images of the breast for cancer diagnosis. Accurate picking of TOFs of
      transmitted ultrasound signals is extremely important to ensure high-resolution
      and high-quality ultrasound sound-speed tomograms. Since manually picking is time
      consuming for large datasets, we developed an improved automatic TOF picker based
      on the Akaike information criterion (AIC), as described in this paper. METHODS:
      We make use of an approach termed multi-model inference (model averaging), based
      on the calculated AIC values, to improve the accuracy of TOF picks. By using
      multi-model inference, our picking method incorporates all the information near
      the TOF of ultrasound signals. Median filtering and reciprocal pair comparison
      are also incorporated in our AIC picker to effectively remove outliers. RESULTS:
      We validate our AIC picker using synthetic ultrasound waveforms, and demonstrate
      that our automatic TOF picker can accurately pick TOFs in the presence of random
      noise with absolute amplitudes up to 80% of the maximum absolute signal
      amplitude. We apply the new method to 1160 in vivo breast ultrasound waveforms,
      and compare the picked TOFs with manual picks and amplitude threshold picks. The
      mean value and standard deviation between our TOF picker and manual picking are
      0.4 micros and 0.29 micros, while for amplitude threshold picker the values are
      1.02 micros and 0.9 micros, respectively. Tomograms for in vivo breast data with
      high signal-to-noise ratio (SNR) ( approximately 25 dB) and low SNR (
      approximately 18 dB) clearly demonstrate that our AIC picker is much less
      sensitive to the SNRs of the data, compared to the amplitude threshold picker.
      DISCUSSION AND CONCLUSIONS: The picking routine developed here is aimed at
      determining reliable quantitative values, necessary for adding diagnostic
      information to our clinical ultrasound tomography device--CURE. It has been
      successfully adopted into CURE, and allows us to generate such values reliably.
      We demonstrate that in vivo sound-speed tomograms with our TOF picks
      significantly improve the reconstruction accuracy and reduce image artifacts.

PMID- 18620724
TI  - Delivery of immunotherapy with peptide-pulsed blood in macaques.
AB  - Simple and effective delivery methods for cellular immunotherapies are needed. We
      assessed ex vivo pulsing of overlapping SIV Gag 15mer peptides onto either whole
      blood or PBMC in 15 randomly assigned SIV-infected macaques. Both delivery
      methods were safe and immunogenic, stimulating high levels of broad and
      polyfunctional Gag-specific CD4 and CD8 T cells. Delivery of overlapping Gag
      peptides via either whole blood or PBMC is suitable for clinical evaluation.

PMID- 18620725
TI  - Reorganization of visual processing in macular degeneration: replication and
      clues about the role of foveal loss.
AB  - We previously reported large-scale reorganization of visual processing (i.e.,
      activation of "foveal" cortex by peripheral stimuli) in two individuals with loss
      of foveal input from macular degeneration [Baker, C.I., Peli, E., Knouf, N., &
      Kanwisher, N. G. (2005). Reorganization of visual processing in macular
      degeneration. Journal of Neuroscience, 25(3), 614-618]. Here, we replicate this
      result in three new individuals. Further, we test the hypothesis that this
      reorganization is dependent on complete loss of foveal input. In two other
      individuals with extensive retinal lesions but some foveal sparing we found no
      evidence for reorganization. We conclude that large-scale reorganization of
      visual processing in MD occurs only in the complete absence of functional foveal
      vision.

PMID- 18620726
TI  - Is immunohistochemical epidermal growth factor receptor expression overestimated
      as a prognostic factor in head-neck squamous cell carcinoma? A retrospective
      analysis based on a tissue microarray of 365 carcinomas.
AB  - Epidermal growth factor receptor is overexpressed in more than 80% of head-neck
      squamous cell carcinoma. Its role as an independent prognostic marker is
      discussed controversially. No standardized evaluation methods are reported. The
      aim of our study was to analyze the prognostic relevance of epidermal growth
      factor receptor expression, using a tissue microarray with more than 300 tumor
      samples. Epidermal growth factor receptor expression was analyzed by
      immunohistochemistry and fluorescence in situ hybridization based on a tissue
      microarray of 365 head-neck squamous cell carcinomas with complete
      clinicopathologic and follow-up data. Multiple independent observers blinded for
      clinical data evaluated epidermal growth factor receptor immunostaining
      semiquantitatively. Cut-off scores for positivity were determined systematically
      by receiver operating characteristic curve analysis and validated by resampling
      of the data. Epidermal growth factor receptor expression cut-off scores for loco
      regional relapse and overall survival were determined to be 60%. No significant
      correlation with clinicopathologic data was found. Independent significant
      differences in loco-regional control and overall survival could not be
      distinguished by epidermal growth factor receptor expression. Epidermal growth
      factor receptor expression could not be confirmed as a significant independent
      prognostic marker in head-neck squamous cell carcinoma using a large tissue
      microarray with 365 head-neck squamous cell carcinomas with complete clinical
      data, an evaluation based on immunohistochemistry and fluorescence in situ
      hybridization by multiple independent observers and systematic determination of
      cut-off scores.

PMID- 18620727
TI  - Different estrogen receptor beta expression in distinct histologic subtypes of
      lung adenocarcinoma.
AB  - Adenocarcinoma is becoming the most common histologic type of lung cancer in both
      sex. Although most cases are seen in smokers, it develops more frequently than
      other histologic types in individuals who have never smoked. This evidence
      suggests that other putative etiologic factors, such as sex hormones, need to be
      investigated. Several subtypes of lung adenocarcinoma have been recently
      described with distinct clinicopathologic features and prognostic implications.
      The purpose of this study is to investigate the role of estrogen receptor beta in
      lung adenocarcinoma, with particular attention paid to its different histologic
      subtypes. Nuclear estrogen receptor beta expression was evaluated by
      immunohistochemistry in 112 lung adenocarcinomas, including both "single subtype"
      and "mixed subtype" samples. Using a 2-level (high/low) score system, estrogen
      receptor beta expression was high in most (75%) adenocarcinomas and turned out to
      be strongly related to the histologic subtypes. In fact, estrogen receptor beta
      expression was low or negative in 68.2% of solid subtypes, whereas it was high in
      76.5% of nonmucinous bronchioloalveolar, in 69.4% of acinar, and in 61.2% of
      papillary patterns (P = .00004). Furthermore, a strong association between
      estrogen receptor beta expression and tumor histologic grade was observed:
      estrogen receptor beta was highly expressed predominantly in well- and moderately
      differentiated tumors (P = .0014). In conclusion, estrogen receptor beta
      expression has distinct patterns in lung adenocarcinoma, suggesting a specific
      role for estrogen receptor beta in the pathogenesis of different histologic
      subtypes of this type of cancer. Moreover, loss of estrogen receptor beta
      expression in poorly differentiated (G3) tumors could represent a crucial step in
      the dedifferentiation process of lung adenocarcinoma.

PMID- 18620728
TI  - Deleted in pancreatic carcinoma locus 4/Smad4 participates in the regulation of
      apoptosis by affecting the Bcl-2/Bax balance in non-small cell lung cancer.
AB  - Deleted in pancreatic carcinoma locus 4 influences tumorigenesis and tumor
      progression by various mechanisms, including apoptosis. The aim of this study is
      to determine whether deleted in pancreatic carcinoma locus 4 participates in
      apoptosis in lung cancer and clarify its relationship with clinical parameters of
      non-small cell lung cancer. Immunohistochemical results revealed that the
      positive rate of deleted in pancreatic carcinoma locus 4 in normal tracheal
      bronchial epithelium (89.5%, 17/19) was much higher than that in tumor tissues
      (63.5%, 33/52) (P < .05) and closely correlated with lymph node metastasis (P <
      .001). These results were further confirmed by Western blot analysis.
      Furthermore, deleted in pancreatic carcinoma locus 4 overexpression was inversely
      associated with Bcl-2 immunostaining (P < .01), and the apoptosis index in
      deleted in pancreatic carcinoma locus 4-positive carcinomas (8.65 +/- 1.46) was
      much higher than that in deleted in pancreatic carcinoma locus 4-negative
      carcinomas (2.12 +/- 0.04) (P < .05). The results of deleted in pancreatic
      carcinoma locus 4 small interfering RNA in A549 cells also showed that deleted in
      pancreatic carcinoma locus 4 could inhibit cell proliferation, decrease Bcl-2
      mRNA and protein expression, and increase Bax messenger RNA and protein
      expression. These findings indicated that Deleted in pancreatic carcinoma locus 4
      might be an important biomarker for malignant transformation and be involved in
      inducing apoptosis by modulating Bcl-2/Bax balance.

PMID- 18620729
TI  - GLUT-1 expression in mesenchymal tumors: an immunohistochemical study of 247 soft
      tissue and bone neoplasms.
AB  - GLUT-1, an erythrocyte-type glucose transporter protein expressed in juvenile
      hemangiomas, has recently been shown to be a sensitive marker of perineurial
      cells and their tumors in a small number of cases. However, GLUT-1 expression has
      not been systematically examined in other mesenchymal neoplasms. Prompted by a
      recent report of GLUT-1 expression in epithelioid sarcoma, a tumor not generally
      felt to show perineurial differentiation, we examined GLUT-1 expression in a wide
      variety of mesenchymal tumors. Sections from 247 mesenchymal tumors of a variety
      of histologic subtypes were retrieved from our archives and immunostained for
      GLUT-1 using heat-induced epitope retrieval and the DAKO ADVANCE detection system
      (DAKO, Carpinteria, CA). Scoring was as follows: negative (<5% of cells), 1+ (5%
      25% of cells), 2+ (25%-50% of cells), and 3+ (>50% of cells). All benign nerve
      sheath tumors showed a peripheral rim of positive normal perineurial cells, with
      2 neurofibromas and 3 schwannomas showing more extensive staining. Three of 4
      perineuriomas showed strong GLUT-1 expression. All juvenile hemangiomas were GLUT
      1 positive. GLUT-1 expression was also seen in a wide variety of benign and
      malignant mesenchymal tumors. However, GLUT-1 expression was absent in
      nonjuvenile hemangioma endothelial tumors and in almost all low-grade lesions
      that enter the histologic differential diagnosis of perineurial tumors, including
      low-grade fibromyxoid sarcoma, dermatofibrosarcoma protuberans, and
      myxofibrosarcoma. We conclude that GLUT-1 expression in mesenchymal tumors is by
      no means specific for perineurial differentiation, but may instead represent
      upregulation of this protein within hypoxic zones, secondary to upstream
      activation of proteins such as hypoxia-inducible factor 1-alpha.

PMID- 18620730
TI  - The combination of high cyclin E and Skp2 expression in breast cancer is
      associated with a poor prognosis and the basal phenotype.
AB  - Gene expression studies have identified a basal phenotype of breast cancer; these
      are hormone receptor and HER2-negative cancers with poor prognosis. High levels
      of cyclin E and Skp2, and low levels of p27 have previously been individually
      associated with both basal-like breast cancer and a poor outcome after diagnosis.
      The goal of this study was to first confirm the prognostic value of these
      biomolecular markers using a breast cancer tissue microarray. Second, we also
      test the hypothesis that the combined phenotype of high cyclin E, low p27, and
      high Skp2 would be a strong predictor of outcome and would be closely associated
      with the basal phenotype of breast cancer. Our cohort consisted of 438 cases of
      breast cancer and the median follow-up was 15.4 years. The tissue microarray was
      constructed from archival tumor blocks and we used commercially available
      antibodies for biomarker immunostaining. Cyclin E was positive in 46% of cases,
      p27 was negative in 62%, and Skp2 was positive in 35%. We found cyclin E and Skp2
      to be prognostic for breast cancer-specific survival in univariate analyses, but
      p27 was not prognostic. The strongest predictor of outcome was the combination of
      cyclin E positive and Skp2 positive (difference in survival of 19% at 10 years, P
      = .0009). This combination was present in 78 (27%) of 288 cases for which data on
      both biomarkers were available. This combination was also highly associated with
      young age at diagnosis, grade 3 tumors, ER-negative status, HER2-negative status,
      and the basal biomarkers epidermal growth factor receptor and cytokeratin 5/6.
      However, in a multivariate model including standard clinicopathologic variables,
      this combination was not found to have independent prognostic significance. In
      conclusion, the combination of high cyclin E and Skp2 expression predicts for
      poor prognosis in breast cancer in univariate analysis only, it is associated
      with high risk features, and it is associated with the basal phenotype.

PMID- 18620731
TI  - Transitional cell carcinoma of the endometrium and endometrial carcinoma with
      transitional cell differentiation: a clinicopathologic study of 5 cases and
      review of the literature.
AB  - To date, only 16 cases of transitional cell carcinoma of the endometrium and
      endometrial carcinoma with transitional cell differentiation have been reported
      in the literature. We reviewed the clinicopathologic features of 5 cases of
      endometrial carcinoma with transitional cell differentiation. The mean age was 68
      years, and all patients presented with postmenopausal bleeding. Macroscopically,
      the tumors were intracavitary and friable. Microscopically, the tumors were
      composed of tightly packed papillary structures with thin fibrovascular cores,
      resembling a transitional cell carcinoma of the urinary tract. One tumor showed
      exclusively transitional cell differentiation, whereas the remaining 4 neoplasms
      showed that the transitional cell carcinoma was admixed with a variable
      proportions of endometrioid adenocarcinoma. Four cases were in FIGO stage IB,
      whereas the remaining tumor infiltrated the uterine cervix (FIGO stage IIB).
      Immunoreactivity was typical of mullerian derivatives (cytokeratin 7 positive,
      cytokeratin 20 negative). p16 protein was positive in all cases, but human
      papillomavirus DNA was not detected in any of the tumors. None of the patients
      developed local recurrence or distant metastases, even though there are too few
      cases of transitional cell carcinoma of the endometrium reported to make any
      statistically valid conclusions about response to therapy and prognosis.
      Transitional cell carcinoma is an unusual variant of endometrial carcinoma, with
      distinctive histologic and immunophenotypic features. Identification of this
      variant broadens the morphological spectrum of epithelial neoplasms of the
      endometrium.

PMID- 18620732
TI  - Progression of renal allograft histology after renal transplantation in recurrent
      and nonrecurrent immunoglobulin A nephropathy.
AB  - Little information is available regarding renal histology in cases of chronic
      allograft dysfunction and graft failure in patients with recurrent immunoglobulin
      A nephropathy. We compared 57 renal allograft biopsies of 44 patients with
      recurrent immunoglobulin A nephropathy to 43 biopsies of 33 patients without
      immunoglobulin A nephropathy recurrence. Clinical parameters such as patient
      demography and biopsy indications did not differ between the 2 groups, with the
      exception of time to biopsy. Renal allograft injury, which was assessed by
      semiquantitative scoring of glomerular, tubulointerstitial, and arteriolar
      changes, increased linearly over time after transplantation in both recurrent and
      nonrecurrent samples. Glomerular injuries were significantly correlated with
      tubulointerstitial injuries in both groups, but the correlation graph reflected
      an increasing gap in the degrees of tubulointerstitial injury between the 2
      groups over time. The levels of glomerulosclerosis, mesangial proliferation, and
      crescent formation were significantly higher in recurrent samples, whereas the
      prevalence of chronic rejection was significantly higher in nonrecurrent samples.
      The presence of segmental sclerosis was associated with significant proteinuria
      in recurrent samples. Graft survival was better in recurrent immunoglobulin A
      nephropathy patients than in nonrecurrent patients (74.4% versus 51%) at 10 years
      after transplantation. In conclusion, slow and progressive glomerular injury is
      the major cause of long-term graft failure in patients with recurrent
      immunoglobulin A nephropathy. In contrast, rapidly increasing tubulointerstitial
      injury is responsible for graft failure in nonrecurrent patients.

PMID- 18620733
TI  - Expression of p63 in anaplastic large cell lymphoma but not in classical
      Hodgkin's lymphoma.
AB  - Immunohistochemical determination of p63 protein is frequently used in the
      pathologic diagnosis of nonhematological solid tumors. In malignant hematological
      disease, p63 expression has been reported in 22% of follicular lymphoma, about
      35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in
      some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell
      lymphoma is a rare disease that accounts for less than 5% of all cases of non
      Hodgkin's lymphoma. There is little information concerning p63 expression in this
      specific type of lymphoma. In some cases, the morphological and phenotypic
      features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma
      are similar, making this differential diagnosis challenging. We studied p63
      expression using a tissue microarray approach in 154 cases of anaplastic large
      cell lymphoma, including 38% anaplastic large cell kinase positive and 62%
      anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty
      eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity
      (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell
      kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42%
      showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of
      CD45-negative/anaplastic large cell kinase-negative null cell-type anaplastic
      large cell lymphoma, a subgroup that offers the most difficulties in the
      differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of
      the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These
      results demonstrate that p63 protein expression is frequently expressed in a
      subset of anaplastic large cell lymphoma cases and may be used as a potential
      tool in the differential diagnosis between anaplastic large cell lymphoma and
      classical Hodgkin's lymphoma.

PMID- 18620734
TI  - Physico-chemical and biological parameters determine metal bioavailability in
      soils.
AB  - The Netherlands Stimulation program on System-oriented Ecotoxicological Research
      focused on three study areas, including two floodplains and a peaty grassland.
      All three areas were polluted with metals, with total soil concentrations often
      exceeding Dutch Intervention Values. The floodplain areas showed a homogeneous
      distribution of metal pollution, while pollution in the peaty area was more
      heterogeneous. This study aimed at establishing possible general trends in metal
      bioavailability by combining results obtained at the three different study sites.
      Available metal concentrations, measured as pore water or 0.01 M CaCl2
      extractable concentrations in soil, were lowest in the floodplain soils, probably
      due to the high pH (> 7.0) and high organic matter (8-30%) and clay contents (13
      42%). In the peaty soil, having a lower soil pH (4.5-6.5) but higher organic
      matter contents (38-60%), in some but not all samples Cu concentrations in pore
      water and Cu and Pb concentrations in 0.01 CaCl2 extracts were higher than in non
      polluted reference areas. Plants in the floodplain areas had only low metal
      concentrations in their leaves, but soil invertebrates and small mammals did
      contain elevated concentrations in their body. Cd showed high levels in
      earthworms, snails and small mammals, while also Cu levels were sometimes
      increased in earthworms, millipedes and small mammals from the floodplain areas.
      Earthworms from the peaty area contained increased levels of Cu and Pb. These
      results suggest that metal bioavailability cannot be predicted from available
      concentrations in pore water or 0.01 M CaCl2 soil extracts, but requires
      measurement of biota and more insight into the biodynamics of metal uptake.

PMID- 18620735
TI  - Identifying the origins of local atmospheric deposition in the steel industry
      basin of Luxembourg using the chemical and isotopic composition of the lichen
      Xanthoria parietina.
AB  - Trace metal atmospheric contamination was assessed in one of the oldest European
      industrial sites of steel production situated in the southern part of the Grand
      Duchy of Luxembourg. Using elemental ratios as well as Pb, Sr, and Nd isotopic
      compositions as tracers, we found preliminary results concerning the trace metal
      enrichment and the chemical/isotopic signatures of the most important emission
      sources using the lichen Xanthoria parietina sampled at 15 sites along a SW-NE
      transect. The concentrations of these elements decreased with increasing distance
      from the historical and actual steel-work areas. The combination of the different
      tracers (major elements, Rare Earth Element ratios, Pb, Sr and Nd isotopes)
      enabled us to distinguish between three principal sources: the historical steel
      production (old tailings corresponding to blast-furnace residues), the present
      steel production (industrial sites with arc electric furnace units) and the
      regional background (baseline) components. Other anthropogenic sources including
      a waste incinerator and major roads had only weak impacts on lichen chemistry and
      isotopic ratios. The correlation between the Sr and Nd isotope ratios indicated
      that the Sr-Nd isotope systems represented useful tools to trace atmospheric
      emissions of factories using scrap metal for steel production.

PMID- 18620736
TI  - Species-specific responses of two benthic invertebrates explain their
      distribution along environmental gradients in freshwater habitats.
AB  - The absence of species in polluted sediments does not necessarily imply exclusion
      due to toxicity. Other factors, like for instance food availability and oxygen
      content, could also partly cause their absence. Hence, knowledge of the
      (combinations of) factors acting on individual organisms is essential in order to
      understand how populations can persist in polluted sediments. In this study
      species-specific responses of two benthic invertebrate species, the mayfly
      Ephoron virgo and the midge Chironomus riparius, to environmental variables were
      compared. It was assessed how these responses determine the distribution of these
      species in polluted sediments. Subsequently, it was discussed how these results
      can assist in the formulation and implementation of policies with respect to the
      ecological risks of pollution to benthic invertebrates. The present study showed
      that sediment pollution is likely to act only occasionally as a single selective
      force reducing the persistence of sensitive species. Yet, it was shown in our
      studies that the pollution level in some tested sediments limits the persistence
      of insects with the sensitivity of E. virgo. In other cases, however, a
      combination of conditions is likely to determine their persistence. As shown here
      for C. riparius, sediment pollution drives this species close to intoxication,
      but a high availability of food enables them to persist very well. The present
      study provides evidence that pollution levels exceeding current Dutch Negligible
      Concentrations may pose a detectable ecological effect at least for sensitive
      benthic invertebrates.

PMID- 18620737
TI  - Behaviour of environmental aquatic nanocolloids when separated by split-flow thin
      cell fractionation (SPLITT).
AB  - A split-flow thin-cell (SPLITT) system in different operating modes was used to
      size fractionate colloids and particles in a lake water. The unperturbed lake
      water sample and eluent fractions (nominally a<1 microm; b>1 microm) were
      analysed with atomic force microscopy (AFM) to assess the quality of the
      separation, in particular to quantify the contamination of the b (>1 microm)
      fraction with nanocolloids (defined here as material <100 nm in size). Particle
      size distribution (PSD) results from AFM indicated that there was substantial
      contamination with nanocolloids. This contamination was, most likely, from
      diffusive transport across flow regimes within the SPLITT and this is supported
      by the fact that vertical distances between laminar flow regimes within the
      SPLITT channel are similar in magnitude, but slightly larger than the mean
      distances travelled by diffusion during the residence time of particles within
      the channel. Nevertheless, AFM surface density data showed that the concentration
      of nanoparticles in the a fraction was 6-9 times higher than in the b fraction,
      depending on the SPLITT mode, indicating that contamination of the b fraction was
      limited. Fluorescence data using monodisperse, low molar mass standards confirm
      the AFM results, with substantial contamination of the b fraction by the
      fluorescent molecular probes. The increased contamination of the b fraction of
      the standard molecular probes compared to natural nanocolloids is likely because
      they are smaller and more diffusive than the average of the natural material. Due
      to this contamination and the likelihood that these small colloids bind a large
      fraction of metals, SPLITT can only be used for metal fractionation and
      speciation in combination with other methods capable of performing further metal
      speciation analysis.

PMID- 18620738
TI  - Serum immunoglobulins and risk of infection: how low can you go?
AB  - OBJECTIVES: To determine the relationship between the levels of serum
      immunoglobulin (Ig) levels and risk of infection. The following 2 main questions
      are addressed: (1) At what level do reduced serum concentrations of the different
      Ig species (focusing on IgA, IgG, and IgM) significantly increase the risk of
      infection above background and (2) For how long can Ig depletion be tolerated
      before an increased risk of infection becomes apparent. METHODS: Information was
      gathered from a search of PubMed and relevant congress abstracts up to and
      including November 2007. RESULTS: Sustained, very low levels of IgA, IgG, or IgM,
      as occur in primary immunodeficiency syndromes, are associated with significantly
      increased risks of infections, primarily respiratory tract infections of
      bacterial origin. Patients with IgG levels <100 mg/dL or IgM levels <20 mg/dL for
      prolonged periods have an increased risk of recurrent and sometimes life
      threatening infectious episodes. Generally, IgA deficiency appears better
      tolerated. Replenishment of IgG in patients with hypogammaglobulinemia reduces
      the infection risk to background if IgG levels are maintained at approximately
      500 mg/dL, although higher levels may be necessary in the presence of certain
      comorbidities. Transient depletion of IgG and/or IgM (or, less commonly, IgA) can
      occur in some patients following the administration of certain drugs, including
      anticonvulsants, corticosteroids, and rituximab. Available evidence suggests that
      such changes are not generally associated with an increased risk of infections.
      CONCLUSIONS: While prolonged, very low levels of IgG and/or IgM are associated
      with a heightened risk of infections, transient or less severe immunodeficiency
      appears to be tolerated in most subjects.

PMID- 18620739
TI  - The potential biomarkers for thromboembolism detected by SELDI-TOF-MS.
AB  - INTRODUCTION: Few studies were concerned about searching for specific biomarkers
      for thromboembolic (arterial and venous) diseases by the use of Surface-Enhanced
      Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS).
      MATERIALS AND METHODS: We screened for potential biomarkers in 69 plasma samples,
      including samples from 20 patients with idiopathetic deep vein thrombosis (DVT),
      20 patients with acute myocardial infarction (AMI), and 29 healthy controls
      without a history of thromboembolism. Pretreated plasma samples were analyzed on
      the Protein Biology System IIc plus SELDI-TOF-MS (Ciphergen Biosystems, Fremont,
      CA). Proteomic spectra of mass to charge ratio (m/z) were generated by the
      application of plasma to immobilized metal affinity capture (IMAC-3) ProteinChip
      arrays activated with copper. RESULTS: A pattern of three biomarkers (m/z: 2 667,
      5 914, and 6 890 Da, respectively) with a total accuracy of 100% was selected
      based on their collective contribution to the optimal separation between patients
      with AMI and healthy controls. Another spattern consisting of only one biomarker
      (m/z: 5 914 Da) could totally discriminate patients with DVT and control
      subjects. For further analysis between patients with AMI and those with DVT, a
      pattern of four biomarkers (m/z: 3 418, 5 271, 33 378, and 68 125 Da,
      respectively) was selected with a total accuracy of 82.5%. CONCLUSIONS: Plasma
      proteomic profiling with SELDI-TOF-MS and ProteinChip technologies provides high
      sensitivity and specificity in discriminating patients with thrombosis and
      healthy subjects. The discovered biomarkers might show great potential for early
      diagnosis of thromboembolic diseases.

PMID- 18620740
TI  - Has the incidence of deep vein thrombosis in patients undergoing total hip/knee
      arthroplasty changed over time? A systematic review of randomized controlled
      trials.
AB  - BACKGROUND: There is a perception in the orthopaedic and thromboembolism
      community that the incidence of deep vein thrombosis (DVT) has decreased in
      patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty
      (THA). OBJECTIVES: To assess the incidence of DVT with warfarin
      thromboprophylaxis over time in patients undergoing elective TKA or THA. METHODS:
      The MEDLINE, EMBASE, and Cochrane Library databases were searched to October
      2006, supplemented by a manual search of reference lists. Two reviewers
      independently extracted data on study characteristics, quality and the frequency
      of total, symptomatic and proximal DVT. RESULTS: Fourteen studies (4,423
      patients) were included. Total and proximal DVT after TKA declined over time (r=
      0.75, p=0.031; r=-0.86, p=0.007 respectively). Total and proximal DVT after THA
      did not change. The risk of developing DVT after TKA was significantly higher
      than after THA (OR 1.85, 95% CI 1.6-2.14; p<0.0001). The risk of developing
      symptomatic DVT after THA was significantly higher than after TKA (OR 2.18, 95%
      CI 1.11-4.27; p=0.012). CONCLUSIONS: The incidence of DVT in patients undergoing
      elective TKA appears to have declined in patients receiving warfarin
      thromboprophylaxis.

PMID- 18620741
TI  - Retroperitoneoscopic right-sided donor nephrectomy with pre- and postcaval renal
      arteries.
AB  - A 56-year-old male donor was evaluated for a kidney donation. Computed tomography
      angiography revealed 2 right renal arteries, 1 coursing in front and 1 behind the
      inferior vena cava. The renal scan showed a lower glomerular filtration rate on
      the right side. We present a technique of retroperitoneoscopic right-sided donor
      nephrectomy.

PMID- 18620742
TI  - Robot-assisted abdominal laparoscopic radical trachelectomy.
AB  - BACKGROUND: Radical trachelectomy in conjunction with pelvic lymphadenectomy is
      an established method to preserve fertility in early cases of cervical cancer.
      The radical trachelectomy is usually performed vaginally despite the initial use
      of laparoscopy for the lymphadenectomy. The complexity of a laparoscopic
      abdominal trachelectomy may explain this dual approach. Here we describe the
      surgical technique of a robot-assisted laparoscopic radical trachelectomy with
      lymphatic mapping using a radiotracer and without a vaginal approach. CASES AND
      SURGICAL TECHNIQUE: Two nulliparous women with early cervical cancer underwent a
      laparoscopic radical trachelectomy and pelvic lymphadenectomy with the assistance
      of the da Vinci robot (Intuitive Surgical Inc, Sunnyvale, CA). After the sentinel
      lymph nodes were found negative on frozen section, the parametria, paracolpia and
      sacrouterine ligaments were dissected sparing the main branches of the uterine
      arteries. Following ligation of the descending branches of the uterine arteries
      the cervix and the vagina were transsected using monopolar diathermia and the
      vagina was sutured to the remaining cervix. Finally, a permanent cerclage was
      placed. Time for surgery was 387 and 358 min respectively. No perioperative
      complications were noted and the postoperative period was uneventful in both
      cases. CONCLUSIONS: Robot-assisted laparoscopic abdominal trachelectomy is a
      feasible alternative to a combined laparoscopic and vaginal approach.

PMID- 18620743
TI  - Tolerance to extensively heated milk in children with cow's milk allergy.
AB  - BACKGROUND: Cow's milk allergy is the most common childhood food allergy.
      Previously we noted that children who outgrew their milk allergy had milk
      specific IgE antibodies primarily directed against conformational epitopes; those
      with persistent milk allergy also had IgE antibodies directed against specific
      sequential epitopes. OBJECTIVE: Because high temperature largely destroys
      conformational epitopes, we hypothesized that some children with milk allergy
      would tolerate extensively heated (baked) milk products. METHODS: Children with
      milk allergy were challenged with heated milk products; heated milk-tolerant
      subjects were subsequently challenged with unheated milk. Heated milk-tolerant,
      unheated milk-reactive subjects ingested heated milk products for 3 months and
      were then re-evaluated. Immune responses were assessed in all subjects; growth
      and intestinal permeability were followed in heated milk-tolerant subjects.
      RESULTS: One hundred children (mean age, 7.5 years; range, 2.1-17.3 years)
      underwent heated milk challenges. Sixty-eight subjects tolerated extensively
      heated milk only, 23 reacted to heated milk, and 9 tolerated both heated and
      unheated milk. Heated milk-reactive subjects had significantly larger skin prick
      test wheals and higher milk-specific and casein-specific IgE levels than other
      groups. At 3 months, subjects ingesting heated milk products had significantly
      smaller skin prick test wheals and higher casein-IgG(4) compared with baseline;
      other immunologic parameters, growth, and intestinal permeability were not
      significantly different. Heated milk-reactive subjects had more severe symptoms
      during heated milk challenge than heated milk-tolerant subjects experienced
      during their unheated milk challenge. CONCLUSION: The majority (75%) of children
      with milk allergy tolerate heated milk.

PMID- 18620744
TI  - Increase in inflammatory mediator concentrations in exhaled breath condensate
      after allergen inhalation.
AB  - BACKGROUND: Although a number of studies have been carried out to examine the
      baseline concentrations of inflammatory mediators in asthmatic patients, the
      clinical utility of exhaled breath condensate (EBC) in allergen-induced
      bronchoconstriction has not yet been clarified. OBJECTIVE: We examined whether
      the release of inflammatory mediators can be detected in EBC after allergen
      induced bronchoconstriction in asthmatic patients. METHODS: We quantified mast
      cell-associated mediators in EBC and their corresponding urinary metabolites
      before and after allergen inhalation. RESULTS: Early asthmatic responses (EARs)
      caused significant increases in the concentrations of cysteinyl leukotrienes
      (CysLTs; median, 10.4 vs 99.0 pg/mL; P < .0001) and prostaglandin D(2) (PGD(2);
      median, 2.26 vs 8.72 pg/mL; P = .0077), but not that of histamine, from baseline
      concentrations. Significant increases in the concentrations of urinary
      leukotriene E(4) and 9alpha, 11beta-prostaglandin F(2) were detected in patients
      with EARs. However, the percentage increases in the concentrations of CysLTs and
      PGD(2) in EBC did not correlate with those of their corresponding urinary
      metabolites. The increases in concentrations of CysLTs and PGD(2) in EBC in
      patients with EARs correlated with each other and correlated with the extent of
      decrease in FEV(1). An insignificant difference in tyrosine concentration before
      and after the inhalation test demonstrated that errors caused by dilution of
      inflammatory mediators are negligibly small in EBC collected over a short period.
      CONCLUSION: In patients with allergen-induced EARs, pulmonary generation of mast
      cell-associated mediators can be evaluated by quantifying CysLTs and PGD(2) in
      EBC, suggesting that the quantification of EBC mediators might be useful in
      monitoring acute asthmatic airway inflammation.

PMID- 18620745
TI  - Repressor of GATA regulates TH2-driven allergic airway inflammation and airway
      hyperresponsiveness.
AB  - BACKGROUND: Studies of human asthma and of animal models of allergic
      inflammation/asthma highlight a crucial role for T(H)2 cells in the pathogenesis
      of allergic asthma. Repressor of GATA (ROG) is a POZ (BTB) domain-containing
      Kruppel-type zinc finger family (or POK family) repressor. A repressive function
      to GATA3, a master transcription factor for T(H)2 cell differentiation, is
      indicated. OBJECTIVE: The aim of this study was to clarify the regulatory roles
      of ROG in the pathogenesis of T(H)2-driven allergic diseases, such as allergic
      asthma. METHODS: We examined allergic airway inflammation and airway
      hyperresponsiveness (AHR) in 3 different mouse models, which use either ROG
      deficient (ROG(-/-)) mice, ROG transgenic mice, or adoptive transfer of cells.
      RESULTS: In ROG(-/-) mice T(H)2 cell differentiation, T(H)2 responses,
      eosinophilic airway inflammation, and AHR were enhanced. In ROG transgenic mice
      the levels of eosinophilic airway inflammation and AHR were dramatically reduced.
      Furthermore, adoptive transfer of T(H)2 cells with increased or decreased levels
      of ROG expression into the asthmatic mice resulted in reduced or enhanced airway
      inflammation, respectively. CONCLUSION: These results indicate that ROG regulates
      allergic airway inflammation and AHR in a negative manner, and thus ROG might
      represent another potential therapeutic target for the treatment of asthmatic
      patients.

PMID- 18620746
TI  - Influence of surface treatments and resin cement selection on bonding to densely
      sintered zirconium-oxide ceramic.
AB  - OBJECTIVES: To evaluate the effect of surface conditioning on the microtensile
      bond strength of zirconium-oxide ceramic to dual-cured resin cements. METHODS:
      Eighteen cylinder-shaped zirconium-oxide ceramic blocks (Cercon Zirconia,
      Dentsply) were treated as follows: (1) Sandblasting with 125 microm aluminum
      oxide (Al(2)O(3)) particles; (2) tribochemical silica coating using 50 microm
      Al(2)O(3) particles modified by silica; (3) no treatment. Each ceramic cylinder
      was duplicated in composite resin (Tetric Evo Ceram, Ivoclar-Vivadent) using a
      silicon mold. Composite cylinders were bonded to conditioned ceramics using: (1)
      Calibra (Densply Caulk); (2) Clearfil Esthetic Cement (Kuraray); (3) Rely x
      Unicem (3M ESPE). After 24h bonded specimens were cut into microtensile sticks
      that were loaded in tension until failure. Data were analyzed using two-way ANOVA
      and Student-Newman-Keuls test for multiple comparisons (p<0.05). Failure mode was
      recorded and the interfacial morphology of debonded specimens was observed using
      a scanning electron microscope (SEM). Surface topography and ceramic average
      surface roughness were analyzed under an atomic force microscope (AFM). RESULTS:
      Significant changes in zirconia surface roughness occurred after sandblasting
      (p<0.001). Bond strength of Clearfil cement to zirconia was significantly higher
      than that of Rely x Unicem and Calibra, regardless of the surface treatment
      (p<0.001). When using Calibra, premature failures occurred in non-treated and
      silica coated zirconia surfaces. SIGNIFICANCE: The phosphate monomer-containing
      luting system (Clearfil Esthetic Cement) is recommended to bond zirconia ceramics
      and surface treatments are not necessary.

PMID- 18620747
TI  - Rheological properties of experimental Bis-GMA/TEGDMA flowable resin composites
      with various macrofiller/microfiller ratio.
AB  - OBJECTIVES: The purpose of this study was to investigate the rheological behavior
      of resin composites and to evaluate the influence of each component, organic as
      well as inorganic, on their viscoelastic properties by testing model experimental
      formulations. METHODS: Several unfilled mixtures of 2,2-bis-[4-(methacryloxy-2
      hydroxy-propoxy)-phenyl]-propane (Bis-GMA) and triethylene glycol dimethacrylate
      (TEGDMA) were prepared as well as experimental flowable resin composites using a
      Bis-GMA/TEGDMA 50/50 wt% mixture as organic fraction filled at 60% in weight with
      varying ratios of silanated barium glass (1 microm) and partially hydrophobic
      fumed silica (0.1 microm). Their rheological properties were investigated using
      dynamic oscillatory rheometers. Transmission electron microscopy (TEM) was also
      performed to investigate the spatial organization of the filler particles.
      RESULTS: Unfilled Bis-GMA/TEGDMA mixtures all showed a Newtonian behavior. The
      experimental flowable resin composites were non-Newtonian, shear-thinning fluids.
      As the quantity of microfiller increased, the viscosity increased and the shear
      thinning behavior increased as well. In addition, the experimental composites
      showed thixotropy, i.e. their viscosity is a function of time after deformation.
      All these properties were not specifically linked to the creation and destruction
      of a visible network between inorganic particles, as no difference could be seen
      between particles' spatial organization at the equilibrium rest state or
      immediately after deformation. SIGNIFICANCE: The complex viscoelastic properties
      of resin composites are due to interactions between microfiller and monomer
      molecules. Modifying the chemical and physical properties of the particles'
      surface could possibly improve their flow properties and thus their clinical
      handling performances.

PMID- 18620748
TI  - High-strength CAD/CAM-fabricated veneering material sintered to zirconia copings-
      a new fabrication mode for all-ceramic restorations.
AB  - OBJECTIVES: With this in vitro study the fracture strength of zirconia-based
      crown copings being veneered with a CAD/CAM generated high-strength ceramic cap
      by sintering is compared with anatomically identical zirconia-based crowns, which
      were either overpressed or veneered by the layering technique for completion.
      METHODS: A 1.2mm, 360 degrees chamfer preparation was performed on a second
      maxillary molar and was dublicated 15 times in a cobalt-chromium-alloy. A sample
      of 45 zirconia copings was produced and divided into three groups. In the first
      group (VT) zirconia copings received conventional veneering in layering
      technique, in the second group the veneering porcelain was pressed over the
      zirconia coping (PT), and for the third group (ST) a CAD/CAM-fabricated high
      strength anatomically shaped veneering cap was sintered onto the zirconia coping.
      All crowns were cemented conventionally onto their dies and tested in the
      universal testing machine until clinical failure. The fracture load data were
      compared by a one-way analysis of variance and a multiple comparison posthoc test
      (alpha<0.05). RESULTS: Specimens from group VT showed a mean (S.D.) fracture load
      of 3700.39 (1238.72) N, group OT 3523.73 (1181.11) N and group ST 6262.67
      (2257.42) N. The difference between groups VT/OT and ST were statistically
      significant (P<0.001). SIGNIFICANCE: The new CAD/CAM-fabricated bilayered
      restorations (ST) were superior to the present techniques (VT and OT) in terms of
      fracture load and offer the possibility to produce cost-effective crowns and
      fixed partial dentures with a potential lower risk of chippings.

PMID- 18620749
TI  - Marginal and internal fits of fixed dental prostheses zirconia retainers.
AB  - OBJECTIVES: CAM (computer-aided manufacturing) and CAD (computer-aided
      design)/CAM systems facilitate the use of zirconia substructure materials for all
      ceramic fixed partial dentures. This in vitro study compared the precision of fit
      of frameworks milled from semi-sintered zirconia blocks that were designed and
      machined with two CAD/CAM and one CAM system. METHODS: Three-unit posterior fixed
      dental prostheses (FDP) (n=10) were fabricated for standardized dies by: a
      milling center CAD/CAM system (Etkon), a laboratory CAD/CAM system (Cerec InLab),
      and a laboratory CAM system (Cercon). After adaptation by a dental technician,
      the FDP were cemented on definitive dies, embedded and sectioned. The marginal
      and internal fits were measured under an optical microscope at 50x magnification.
      A one-way analysis of variance (ANOVA) was used to compare data (alpha=0.05).
      RESULTS: The mean (S.D.) for the marginal fit and internal fit adaptation were:
      29.1 microm (14.0) and 62.7 microm (18.9) for the milling center system, 56.6
      microm (19.6) and 73.5 microm (20.6) for the laboratory CAD/CAM system, and 81.4
      microm (20.3) and 119.2 microm (37.5) for the laboratory CAM system. One-way
      ANOVA showed significant differences between systems for marginal fit (P<0.001)
      and internal fit (P<0.001). SIGNIFICANCE: All systems showed marginal gaps below
      120 microm and were therefore considered clinically acceptable. The CAD/CAM
      systems were more precise than the CAM system.

PMID- 18620750
TI  - Design and evaluation of polypseudorotaxanes of pegylated insulin with
      cyclodextrins as sustained release system.
AB  - Supramolecular assemblies have attracted a great attention, due to their
      intriguing topologies and their application in various fields such as
      nanodevices, sensors, molecular switches, and drug delivery systems. In this
      study, we prepared the monosubstituted insulin with poly(ethylene glycol) (PEG,
      MW about 2200) and its cyclodextrin (CyD) polypseudorotaxanes. The pegylated
      insulin formed polypseudorotaxanes with alpha- and gamma-CyDs, by inserting one
      PEG chain in the alpha-CyD cavity and two PEG chains in the gamma-CyD cavity. The
      pegylated insulin/alpha- and gamma-CyD polypseudorotaxanes were less soluble in
      water and the release rate of the drug decreased in the order of drug alone>the
      gamma-CyD polypseudorotaxane>the alpha-CyD polypseudorotaxane. The plasma levels
      of the pegylated insulin after subcutaneous administration of the gamma-CyD
      polypseudorotaxane to rats were significantly prolonged, accompanying an increase
      in the area under plasma concentration-time curve, which was clearly reflected in
      the prolonged hypoglycemic effect. The results indicated that the pegylated
      insulin/CyD polypseudorotaxanes can work as a sustained drug release system, and
      the polypseudorotaxane formation with CyDs may be useful as a sustained drug
      delivery technique for other pegylated proteins and peptides.

PMID- 18620751
TI  - Altered stored calcium release in skeletal myotubes deficient of triadin and
      junctin.
AB  - Triadin and junctin are integral sarcoplasmic reticulum membrane proteins that
      form a macromolecular complex with the skeletal muscle ryanodine receptor (RyR1)
      but their roles in skeletal muscle calcium homeostasis remain incompletely
      understood. Here we report that delivery of siRNAs specific for triadin or
      junctin into C2C12 skeletal myoblasts reduced the expression of triadin and
      junctin in 8-day-old myotubes by 80 and 100%, respectively. Knocking down either
      triadin or junctin in these cells reduced Ca2+ release induced by depolarization
      (10mM KCl) by 20-25%. Unlike triadin knockdown myotubes, junctin knockdown and
      junctin/triadin double knockdown myotubes also had reduced Ca2+ release induced
      by 400 microM 4-chloro-m-cresol, 10mM caffeine, 400 microM UTP, or 1 microM
      thapsigargin. Thus, knocking down junctin compromised the Ca2+ stores in the
      sarcoplasmic reticulum of these cells. Our subsequent studies showed that in
      junctin knockdown myotubes at least two sarcoplasmic reticulum proteins (RyR1 and
      skeletal muscle calsequestrin) were down-regulated while these proteins' mRNA
      expression was not affected. The results suggest that triadin has a role in
      facilitating KCl depolarization-induced Ca2+ release in contrast to junctin which
      has a role in maintaining sarcoplasmic reticulum Ca2+ store size in C2C12
      myotubes.

PMID- 18620752
TI  - Erythropoietin and cancer, a double-edged sword.
AB  - This editorial is focused on the double controversial action of erythropoietin,
      acting as anticancer agent and as a promoting cancer agent.

PMID- 18620753
TI  - Do chronic conditions increase young children's risk of being maltreated?
AB  - OBJECTIVE: To examine whether and to what extent specific chronic health
      conditions place young children at risk of maltreatment. METHODS: The study used
      a sample of Illinois children (born between January 1990 and March 1996) who were
      through age 3 continuously enrolled in Medicaid, a public health insurance
      program for low-income families. The study used "paid claims" data and ICD-9-CM
      health codes to identify children with one or more of three chronic conditions:
      chronic physical illness, developmental delay/mental retardation (dd/mr), and
      behavior/mental health conditions (b/mh). The analysis used Cox proportional
      hazard models to estimate the risk of substantiated child maltreatment that each
      of these health conditions confer on children under age 6. RESULTS: Among
      children under age 6, 24.1% had chronic physical health conditions, 6.1% had b/mh
      conditions, and 4.2% had dd/mr. Among the children, 11.7% were maltreated (abused
      or neglected). Children with b/mh conditions were 1.95 times more likely than
      children without such conditions to be victims of child abuse or neglect.
      Children with chronic physical health conditions were 1.1 time more likely to be
      maltreated (p<or=.001). In contrast, children with dd/mr were not at an increased
      risk of maltreatment. Further, if the child had a prior history of abuse or
      neglect before age 3 and was also diagnosed with a behavioral health condition,
      that child was 10 times more likely to be maltreated again (relative risk of 9.2,
      p<or=.0001). CONCLUSIONS: Behavioral/mental health conditions placed low-income
      children under age 6 at the highest risk of abuse or neglect. Developmental
      delay/mental retardation, however, did not appear to increase the risk of
      maltreatment, while chronic physical health conditions increased the risk
      slightly among this group of children. Therefore, identified behavior/mental
      health in young, low-income children should be considered a risk factor for
      potential abuse to pediatricians and other health professionals. Child protection
      agencies should be trained to identify behavioral/mental health conditions of
      children. PRACTICE IMPLICATIONS: Chronic behavioral/mental health conditions
      place young children at heightened risk of abuse or neglect. Early detection of
      mental or psychosocial health conditions is mandated by the Individuals with
      Disabilities Education Act (IDEA), a federal law that governs how state and
      public agencies provide services to children with disabilities. Given the higher
      risk of abuse and neglect among children with behavioral/mental health
      conditions, clinicians should give added scrutiny to these children. Child
      protection agencies should also be trained to identify behavioral/mental health
      conditions, and more states should record disability status in their abuse
      records.

PMID- 18620754
TI  - One-dimensional copper(II) coordination polymers bridged both by mu-trans
      oxamidates and phenyldicarboxylates: Synthesis, crystal structure and DNA binding
      studies.
AB  - Two new one-dimensional copper(II) polymers with formulae of
      [Cu(2)(H(2)O)(2)(dmapox)(ipa)(2)](n) (1) and [Cu(2)(H(2)O)(2)(dmapox)(tpa)(2)](n)
      (2), where dmapox, ipa and tpa stand for the dianion of N,N'-bis[3
      (dimethylamino)propyl]oxamide, isophthalic acid and terephthalic acid
      respectively, have been synthesized and characterized by elemental analysis,
      conductivity measurement, IR and electronic spectral studies. The crystal
      structures of the two complexes have been determined by X-ray single-crystal
      diffraction. The structures of 1 and 2 consist of one-dimensional copper(II)
      coordination polymeric chain constructed both by the bis-tridentate trans-dmapox
      and bis-monodentate phenyldicarboxylate bridging ligands. In the two complexes,
      the environment around the copper(II) atoms can be described as distorted square
      pyramid and the Cu...Cu separations through mu-trans-dmapox and
      phenyldicarboxylato bridging ligands are 5.245(5) A and 8.212(3) A for 1,
      5.237(8) A and 11.171(1) A for 2, respectively. The binding properties of the two
      copper(II) polymers with herring sperm DNA (HS-DNA) have been investigated by
      using absorption and emission spectral and electrochemical techniques and
      viscometry. The results show that the two copper(II) complexes interact with the
      HS-DNA in the mode of intercalation with the intrinsic binding constants of
      1.22(+/-0.2)x10(4)M(-1) and 1.45(+/-0.3)x10(4)M(-1) for 1 and 2, respectively.

PMID- 18620755
TI  - Probability distributions of the logarithm of inter-spike intervals yield
      accurate entropy estimates from small datasets.
AB  - The maximal information that the spike train of any neuron can pass on to
      subsequent neurons can be quantified as the neuronal firing pattern entropy.
      Difficulties associated with estimating entropy from small datasets have proven
      an obstacle to the widespread reporting of firing pattern entropies and more
      generally, the use of information theory within the neuroscience community. In
      the most accessible class of entropy estimation techniques, spike trains are
      partitioned linearly in time and entropy is estimated from the probability
      distribution of firing patterns within a partition. Ample previous work has
      focused on various techniques to minimize the finite dataset bias and standard
      deviation of entropy estimates from under-sampled probability distributions on
      spike timing events partitioned linearly in time. In this manuscript we present
      evidence that all distribution-based techniques would benefit from inter-spike
      intervals being partitioned in logarithmic time. We show that with logarithmic
      partitioning, firing rate changes become independent of firing pattern entropy.
      We delineate the entire entropy estimation process with two example neuronal
      models, demonstrating the robust improvements in bias and standard deviation that
      the logarithmic time method yields over two widely used linearly partitioned time
      approaches.

PMID- 18620756
TI  - Molecular diversity of TEX101, a marker glycoprotein for germ cells monitored
      with monoclonal antibodies: variety of the molecular characteristics according to
      subcellular localization within the mouse testis.
AB  - TEX101 was characterized as a unique germ cell marker molecule using the specific
      monoclonal antibody (mAb), TES101. Although this mAb has strong
      affinity/specificity for TEX101, TES101 mAb loses its reactivity under reducing
      conditions. In this study, we have generated new mAbs against TEX101 to
      compensate for the shortcomings of the TES101 mAb using different approaches.
      First, we immunized mice with the antigen on a baculovirus expression system and
      isolated new anti-TEX101 mAbs, 6002 and 6035. Second, we raised the mAb Ts4 from
      spleen cells of an immunologically naive old mouse. Western blot analysis
      revealed that the new mAbs possess immunoreactivity under reducing/non-reducing
      conditions. Immunopositive staining of the mAbs against Bouin-fixed sections was
      observed in spermatocytes, spermatids and testicular spermatozoa, but not in
      other cells, similar to paraformaldehyde (PFA)-fixed frozen sections stained with
      TES101 as previously reported. However, whereas the mAbs 6002/6035 mainly showed
      immunoreactivity only in spermatocytes in PFA-fixed frozen sections, the
      reactivity of the mAbs to spermatids and testicular spermatozoa was clearly
      recovered when the PFA-fixed sections were autoclaved or treated with SDS.
      Peptide mapping and deglycosylation analysis indicated that the epitopes for
      TES101, 6002 and 6035 are located within TEX101(25-94), whereas Ts4 recognized N
      linked carbohydrate moieties on TEX101 in Triton X-100-soluble mouse testicular
      extracts but not in the extracellular or water-soluble fractions. These results
      suggest strongly that the molecular association or structure of N-linked
      carbohydrate moieties of TEX101 varies according to its subcellular localization
      within the seminiferous tubules. These new mAbs will be valuable tools for
      further analysis of TEX101, including its function(s).

PMID- 18620757
TI  - Osteopontin immunoreactivity in the ileum and ileocecal lymph node of dairy cows
      naturally infected with Mycobacterium avium subsp. paratuberculosis.
AB  - Osteopontin (Opn), a highly acidic glycoprotein, promotes cellular adhesion and
      recruitment and has been shown to be upregulated in the granulomas of
      mycobacterial infections. Johne's disease, caused by Mycobacterium avium subsp.
      paratuberculosis (MAP), is associated with granulomatous enteritis. The objective
      of this experiment was to identify Opn in the ileum and ileocecal lymph node
      (ICN) of dairy cows naturally infected with MAP and to compare the frequency and
      intensity of staining between noninfected healthy controls, subclinical and
      clinical cows. Sections from these three groups of animals were selected from a
      tissue archive. Immunohistochemical analysis was used to determine the location
      and expression of Opn. The frequency and intensity of staining was also reported.
      Confirmation of acid-fast bacilli in the tissue sections was achieved by the
      Ziehl-Neelsen method. Within the ileal tissue, macrophages, lymphocytes, and
      plasma cells stained positive for Opn. Clinical cows expressed Opn at a greater
      frequency in the lamina propria. Control and subclinical cows did not have areas
      of granulomatous inflammation but cells staining for Opn were equally intense for
      the three groups. The frequency of staining for Opn in the ICN was not affected
      by MAP infection. Results of this study confirm for the first time, the
      expression of Opn in the ileum and ICN of MAP-infected cattle.

PMID- 18620758
TI  - Management of extra sellar craniopharyngioma masquerading as hypertrophied
      adenoid tissue in a 6-year-old boy.
AB  - Described here is a rare case of a craniopharyngioma of the nasopharynx and the
      sphenoid sinus and its surgical resection via an endoscopic, transnasal,
      transphenoidal approach. The study design is case report. Craniopharyngiomas are
      histologically benign, extra-axial slow growing tumours of the sellar and the
      supra sellar space. Patients usually present with symptoms of neurologic,
      ophthalmologic or endocrine dysfunction. Possibility of the occurrence of such
      rare tumours needs to be always kept in mind while dealing with nasopharyngeal
      masses. The endoscopic transnasal transsphenoidal approach has been found to be
      associated with very low morbidity in experienced hands. Long term follow up of
      these patients is mandatory, because of the tendency of craniopharyngioma's to
      recur. Here, the patient was a 10-year-old boy, who had none of the above
      symptoms and was operated upon previously for the same complaints, with no relief
      in symptoms.

PMID- 18620759
TI  - Multiparametric comparison of cold knife tonsillectomy, radiofrequency excision
      and thermal welding tonsillectomy in children.
AB  - OBJECTIVE: This is a prospective study evaluating certain intraoperative and
      postoperative parameters, comparing the relatively new technique of thermal
      welding tonsillectomy with cold knife tonsillectomy, and radiofrequency excision
      in pediatric population. METHODS: Ninety children aged from 5 through 13 years
      were enrolled a randomized prospective trial comparing cold knife tonsillectomy,
      radiofrequency excision, and thermal welding tonsillectomy. Indications included
      recurrent acute tonsillitis and/or obstructive sleep apnea syndrome. All
      techniques were compared by means of length of surgery time, blood loss,
      postoperative bleeding and postoperative pain. RESULTS: Sixty-eight patients
      underwent tonsillectomy for obstructive sleep apnea, whereas 22 children
      underwent tonsillectomy due to recurrent acute tonsillitis. Median values of all
      variables tested, length of surgery time, blood loss, postoperative bleeding and
      postoperative pain, were found to differ significantly among the three surgical
      techniques (P<0.001). Particularly, a statistically significant higher median
      duration (P<0.001) and intraoperative blood loss (P<0.001), as well as, a
      statistically significant lower median pain score in each day tested (P<0.001) of
      the cold knife group, compared to each one of the other two groups, were found.
      Tissue welding and radiofrequency groups did not differ significantly in any
      aspect tested. CONCLUSIONS: Both thermal welding and radiofrequency excision
      techniques have shown comparable results regarding intraoperative blood loss,
      postoperative hemorrhage, and pain. Compared with cold knife tonsillectomy,
      welding and radiofrequency excision techniques were associated with less
      intraoperative blood loss and duration, though cold knife tonsillectomy seems to
      prevail over the two techniques in terms of the postoperative pain.

PMID- 18620760
TI  - Cidofovir modulated gene expression in recurrent respiratory papillomatosis.
AB  - OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is a benign aerodigestive
      tract neoplasm. Cidofovir, an antiviral drug, has demonstrated efficacy in
      slowing and/or reducing RRP recurrence. This investigation examined the
      differential gene expression of RPP before and after cidofovir use in vivo.
      METHODS: Papillomas were harvested from two patients pre- and post-cidofovir
      treatment. RNA was extracted from the tissues and separate Serial Analysis of
      Gene Expression (SAGE) libraries created. Overall gene expression as well as
      relative gene expression in the four libraries was compared. RESULTS: Over 19,000
      tags were found in each of the libraries, with over 6000 unique transcripts
      identified in the pre-treatment and over 6000 identified in the post-cidofovir
      libraries of both patient 1 and 2. Following cidofovir treatment, the greatest up
      regulation was in gene families associated with cell proliferation, metabolism,
      transport and response to biotic stimuli. Post-treatment up-regulation was seen
      in numerous specific genes, such as Interferon Regulatory Factor 7 (P=0.000014),
      which has been associated with virus-host interactions, passive viral induction
      of host immune response, and response to DNA damage stimulus. Down-regulation was
      demonstrated in gene families associated with transcription, regulation of
      nucleic acid metabolism, and signal transduction. DISCUSSION: Creation of RRP
      SAGE libraries demonstrates a broad list of genes expressed in RRP, as well as
      significant differences in gene expression after exposure to cidofovir,
      potentially allowing for a more thorough understanding of important genetic
      pathways in RRP treatment. In addition, over 1400 unique transcripts were
      identified, which will facilitate new gene discovery in RRP research.

PMID- 18620762
TI  - Secondary prevention of coronary artery disease in urban Indian primary care.
AB  - BACKGROUND: Although secondary prevention has the potential to substantially
      reduce the risk of coronary events, its impact depends on the extent to which it
      is applied in the community. Presently, there is no information on the frequency
      with which drugs recommended for secondary prevention of CAD are used in the
      setting of primary care in India or other developing countries. Such information
      could help focus attention of physicians on its importance. METHOD: In a
      prospective epidemiologic survey, 134 primary care physicians from 50 randomly
      selected cities distributed throughout India identified outpatients with stable
      CAD and symptoms of angina. Demographic and clinical characteristics, together
      with their treatment were recorded on a standardized questionnaire. RESULTS: In
      406 patients, the number (%, 95% CI) receiving aspirin was, 335 (82.5, 78.2 to
      86.2); b-blockers, 215 (53.0, 48.1 to 57.9); angiotensin converting enzyme
      inhibitors (ACEI), 63 (15.5, 12.0 to 19.0); and statins, 280 (69.0, 61.0 to
      77.0). Hypertension was untreated in 125 patients (33.4, 28.6 to 38.2).
      Combination treatment with any two (of aspirin, b-blocker, statin, ACEI, or
      antihypertensive agent other than b-blocker and ACEI) was received by 249
      patients (61.3, 51.3 to 71.3); and with any three by 21 (5.2, 3.0 to 7.3).
      DISCUSSION: Secondary prevention is under utilized in Indian patents with CAD.
      Against the background of an emerging epidemic, physicians in primary care need
      to increase the use of widely available specific secondary preventive agents
      recommended by guidelines.

PMID- 18620763
TI  - Unexpected pulsatile intracardiac mass.
AB  - We present a curious pulsatile right atrial mass which we found by routine
      transthoracic echocardiography in an asymptomatic woman. Only consecutive section
      planes finally revealed the true nature of this round mass, highlighting the
      general statement that the ultrasonographer should never rely on a single
      ultrasound imaging plane for making a correct diagnosis.

PMID- 18620761
TI  - A rapid point of care immunoswab assay for SARS-CoV detection.
AB  - The emergence of severe acute respiratory syndrome (SARS) resulted in several
      outbreaks worldwide. Early tests for diagnosis were not always conclusive in
      identifying a SARS suspected patient. Nucleocapsid protein (NP) is the most
      predominant virus derived structural protein which is shed in high amounts in
      serum and nasopharyngeal aspirate during the first week of infection. As part of
      such efforts, a simple, easy to use immunoswab method was developed by generating
      a panel of monoclonal antibodies (MAbs), Bispecific MAbs and chicken polyclonal
      IgY antibody against the SARS-CoV nucleocapsid protein (NP). Employing the MAb
      based immunoswab, an NP concentration of 200 pg/mL in saline and pig
      nasopharyngeal aspirate, and 500 pg/mL in rabbit serum were detected. BsMAb-based
      immunoswabs detected an NP concentration of 20 pg/mL in saline, 500 pg/mL in
      rabbit serum and 20-200 pg/mL in pig nasopharyngeal aspirate. Polyclonal IgY
      based immunoswabs detected an NP concentration of 10 pg/mL in pig nasopharyngeal
      aspirate providing the most sensitive SARS point of care assay. Results show that
      the robust immunoswab method of detecting SARS-CoV NP antigen can be developed
      into an easy and effective way of identifying SARS suspected individuals during a
      future SARS epidemic, thereby reducing and containing the transmission. The key
      feature of this simple immunoswab diagnostic assay is its ability to detect the
      presence of the SARS-CoV antigen within 45-60 min with the availability of the
      body fluid samples.

PMID- 18620765
TI  - Switch from abciximab to eptifibatide during percutaneous coronary intervention.
AB  - BACKGROUND: Treatment with glycoprotein (GP) IIb/IIIa inhibitors during
      percutaneous coronary intervention (PCI) reduce ischemic complications and
      improve outcome. Of the GPIIb/IIIa inhibitors abciximab is better documented than
      eptifibatide, but the former is more expensive. The aim of this study was to
      monitor a switch from abciximab to eptifibatide with respect to clinical outcome
      up to six months after PCI. METHODS: All consecutive patients that six months
      before and six months after a switch from abciximab to eptifibatide received
      GPIIb/IIIa inhibitors during and after de novo PCIs were followed for six months
      with respect to clinical outcome. RESULTS: 310 patients received abciximab and
      350 eptifibatide. Baseline characteristics were similar in the two groups. 55% of
      the patients underwent PCI for acute ST-elevation myocardial infarction and 41%
      for unstable coronary artery disease. There were trends for lower mortality among
      abciximab-treated than among the eptifibatide-treated patients during in-hospital
      stay (0.6% vs 2.0%:NS) as well as during the six month follow up (2.3% vs
      3.7%:NS). The combined endpoint of death, myocardial infarction, stroke, repeated
      revascularisation and serious bleeding occurred in 14.9% in the abciximab group
      vs 16.8% in the eptifibatide group (NS). CONCLUSION: The study could not
      demonstrate any significant deterioration of clinical results after a switch from
      abciximab to eptifibatide as routine GPIIb/IIIa inhibition during PCI. With
      respect to the limited number of patients a clinical significant difference
      between the two GPIIb/IIIa inhibitors cannot, however, be excluded.

PMID- 18620766
TI  - Successful cardiac resynchronization with single-site left ventricular pacing in
      children.
AB  - BACKGROUND: Dyssynchronous left ventricular (LV) contraction due to permanent
      right ventricular apex (RVA) pacing or delayed electrical activation as typically
      observed in left bundle brunch block (LBBB) has a negative impact on LV function.
      Objective was to evaluate the impact of epicardial single-site LV pacing in
      children on LV function and resynchronization. PATIENTS: Single-site epicardial
      LV free wall pacing was established in 6 children with congenital heart disease
      and echocardiographic signs of LV dyssynchrony. Reasons for dyssynchrony were
      either long-term RVA pacing (n=5; pacing duration: 7.7+/-2.4 years) or LBBB with
      drug-resistant congestive heart failure (n=1). RESULTS: After 1 month of single
      site LV pacing, LV ejection fraction increased (41+/-6 versus 53+/-8%) and LV
      enddiastolic volume decreased (70+/-22 versus 63+/-18 ml/m(2)) as compared to pre
      implant measurements. Interventricular mechanical delay decreased (67+/-15 versus
      16+/-15 ms) and intraventricular synchrony was restored (septal-to-posterior wall
      motion delay: 312+/-24 versus 95+/-57 ms). Accordingly, circumferential 2D strain
      demonstrated a decrease of LV mechanical delay (201+/-35 versus 99+/-23 ms).
      CONCLUSION: After 1 month of single-site LV pacing, conventional and 2D strain
      derived echocardiographic measurements indicated improved ventricular function
      and synchronization in children with previous RVA pacing or LBBB. Further studies
      are needed to evaluate whether single-site LV pacing may be sufficient for
      resynchronization therapy.

PMID- 18620768
TI  - Field observations during the Bluetongue serotype 8 epidemic in 2006. II.
      Morbidity and mortality rate, case fatality and clinical recovery in sheep and
      cattle in the Netherlands.
AB  - Data collected in the Netherlands during the Bluetongue serotype 8 (BTV-8)
      epidemic indicated that in outbreak cattle herds, predominantly dairy and nursing
      cows were clinically affected and not young stock, beef cattle, beef calves, or
      breeding animals. In outbreak sheep flocks, mainly ewes and--if present--rams,
      were clinically affected and not the lambs. Median morbidity rate in outbreak
      herds was 1.85 per 100 sheep-month at risk and 0.32 per 100 cattle-month at risk
      for sheep and cattle, respectively. The mean proportion of BT-affected animals in
      outbreak herds that recovered from clinical disease was approximately eight times
      higher for cattle compared to sheep in the Netherlands. Median mortality rate in
      outbreak herds was 0.5 per 100 sheep-month at risk of dying and 0 per 100 cattle
      month at risk of dying for sheep and cattle, respectively. Median recovery time
      of both sheep and cattle that recovered from clinical disease in outbreak herds
      was 14 days. Median case fatality was 50% in sheep outbreak flocks and 0% in
      outbreak cattle herds. It is concluded that morbidity and mortality in outbreak
      cattle herds was very limited during the BTV-8 epidemic in the Netherlands in
      2006. In outbreak sheep flocks, morbidity was limited, with exceptions for a few
      flocks. However, almost 50% of the clinically sick sheep died in outbreak sheep
      herds.

PMID- 18620767
TI  - Field observations during the bluetongue serotype 8 epidemic in 2006. I.
      Detection of first outbreaks and clinical signs in sheep and cattle in Belgium,
      France and the Netherlands.
AB  - Starting August 2006, a major epidemic of bluetongue (BT) was identified in North
      West Europe, affecting The Netherlands, Belgium, Germany, Luxembourg and the
      North of France. It was caused by BT virus serotype 8 (BTV-8), a serotype
      previously unknown to the European Union (EU). In this outbreak, the virus caused
      clinical disease in a few individual animals within cattle herds, whereas overt
      clinical disease was usually restricted to sheep. Investigations in Belgium
      suggested that the first clinical signs of BTV-8 appeared mid July 2006 in a
      cattle herd, while the first suspicion of a BT-outbreak in Belgium was reported
      on 17 August 2006. In the first 10 BTV-8 outbreaks in the Netherlands, the owners
      indicated that the first clinical signs started approximately 12-17 days before a
      suspicion was reported to the veterinary authorities via a veterinary
      practitioner. In BTV-8 affected sheep flocks, erosions of the oral mucosa, fever,
      salivation, facial and mandibular oedema, apathy and tiredness, mortality, oedema
      of the lips, lameness, and dysphagia were among the most frequent clinical signs
      recorded. The most prominent clinical signs in BTV-8 affected cattle herds were:
      crusts/lesions of the nasal mucosa, erosions of lips/crusts in or around the
      nostrils, erosions of the oral mucosa, salivation, fever, conjunctivitis,
      coronitis, muscle necrosis, and stiffness of the limbs. Crusts/lesions of nasal
      mucosa, conjunctivitis, hyperaemic/purple coloration and lesions of the teats,
      and redness/hypersensitivity of the skin were relatively more seen on outbreak
      farms with cattle compared to sheep. Mortality, oedema of the head and ears,
      coronitis, redness of the oral mucosa, erosions/ulceration of tongue mucosa,
      purple coloration of the tongue and tongue protrusion and dyspneu were relatively
      more seen on outbreak farms with sheep compared to cattle.

PMID- 18620769
TI  - Grana Padano cheese whey starters: microbial composition and strain distribution.
AB  - The aim of this work was to evaluate the species composition and the genotypic
      strain heterogeneity of dominant lactic acid bacteria (LAB) isolated from whey
      starter cultures used to manufacture Grana Padano cheese. Twenty-four Grana
      Padano cheese whey starters collected from dairies located over a wide geographic
      production area in the north of Italy were analyzed. Total thermophilic LAB
      streptococci and lactobacilli were quantified by agar plate counting. Population
      structure of the dominant and metabolically active LAB species present in the
      starters was profiled by reverse transcriptase, length heterogeneity-PCR (RT-LH
      PCR), a culture-independent technique successfully applied to study whey starter
      ecosystems. The dominant bacterial species were Lactobacillus helveticus,
      Lactobacillus delbrueckii subsp. lactis, Streptococcus thermophilus, and
      Lactobacillus fermentum. Diversity in the species composition allowed the whey
      cultures to be grouped into four main typologies, the one containing L.
      helveticus, L. delbrueckii subsp. lactis, and S. thermophilus being the most
      frequent one (45% of the cultures analyzed), followed by that containing only the
      two lactobacilli (40%). Only a minor fraction of the cultures contained L.
      helveticus alone (4%) or all the four LAB species (11%). Five hundred and twelve
      strains were isolated from the 24 cultures and identified by M13-PCR
      fingerprinting coupled with 16S rRNA gene sequencing. Most of the strains were L.
      helveticus (190 strains; 37% of the total), L delbrueckii subsp. lactis (90
      strains; 18%) and S. thermophilus (215 strains; 42%). This result was in good
      agreement with the qualitative whey starter composition observed by RT-LH-PCR.
      M13-PCR fingerprinting indicated a markedly low infra-species diversity, i.e. the
      same biotypes were often found in more than one culture. The distribution of the
      biotypes into the different cultures was mainly dairy plant-specific rather than
      correlated with the different production areas.

PMID- 18620770
TI  - Anti-Campylobacter, anti-aerobic, and anti-oxidative effects of roselle calyx
      extract and protocatechuic acid in ground beef.
AB  - The inhibitory effect of roselle calyx extract and protocatechuic acid against
      susceptible and antibiotic-resistant Campylobacter jejuni, C. coli and C. fetus
      in agar plate and ground beef was examined. The minimal inhibitory concentrations
      of roselle calyx extract and protocatechuic acid against susceptible and
      antibiotic-resistant Campylobacter species were in the range of 96-152 and 20-44
      microg/ml, respectively. Temperature treatments from 25 to 100 degrees C did not
      affect the anti-Campylobacter activity of protocatechuic acid. In ground beef
      stored at 15 degrees C for 6 days, roselle calyx extract and protocatechuic acid
      inhibited the survival and growth of aerobes, and susceptible and antibiotic
      resistant Campylobacter species, in which protocatechuic acid exhibited dose
      dependent effect. Both roselle calyx extract and protocatechuic acid decreased
      lipid oxidation levels in ground beef, in which protocatechuic acid also
      exhibited dose-dependent effect. The addition of roselle calyx extract or
      protocatechuic acid did not affect cooking loss, pH value, sensory attributes and
      content of fat, protein and moisture of beef samples during storage at 4 degrees
      C for 15 days. These data support that roselle calyx extract and protocatechuic
      acid may be used for muscle foods to prevent contamination from Campylobacter and
      aerobes, as well as delay lipid oxidation.

PMID- 18620771
TI  - The residual occurrences of Bacillus thuringiensis biopesticides in food and
      beverages.
AB  - In 2006, 54 pasteurized full fat milk samples, 40 ice-cream samples, and two
      green-tea beverage samples were analyzed and a total of 19 Bacillus thuringiensis
      like strains were isolated, nine from seven pasteurized milks, one from an ice
      cream with peach pulp and juice, and nine from two green-tea beverages. These
      strains were classified as B. thuringiensis, contained the cry1A gene and
      produced crystal inclusions during sporulation. All strains were characterized by
      a serotyping test, SDS-PAGE, random amplified polymorphic DNA, and enterotoxic
      gene PCR analysis. Most isolates produced bipyramidal crystals and belonged to
      serotypes H3a3b, H5a5b, or H7. Furthermore, two strains from pasteurized full fat
      milks and three strains from green-tea beverages were indistinguishable from the
      B. thuringiensis subsp. kurstaki strains isolated from commercial biopesticides
      (Kaiyan, Qiangdi, Lvpuan and Sutai), suggesting the residual occurrences of B.
      thuringiensis from biopesticides in food and beverages.

PMID- 18620772
TI  - Bacteriocin-producing Lactobacillus strains isolated from poto poto, a Congolese
      fermented maize product, and genetic fingerprinting of their plantaricin operons.
AB  - Thirty one bacteriocin-producing Lactobacillus isolates were identified among 135
      lactobacilli isolated from the Congolese fermented maize product poto poto,
      during the preparation and from the finished product. Using species-specific PCR
      and 16S rRNA gene sequencing, 28 and 3 isolates were identified as L. plantarum
      and L. fermentum, respectively. Cluster analysis of RAPD-PCR fingerprints
      revealed two main groups (G1 and G2) plus the L. fermentum isolate C4-13. Group
      G1 contained 23 isolates with a similarity coefficient > 74.5%, and could be
      divided in two subgroups (G1-1, G1-2) each with several branches, plus the L.
      plantarum isolate C11. Group G2 contained 8 isolates with a similarity
      coefficient > 86%, with two main branches. Using PCR amplification with specific
      primers, several genes of the plantaricin cluster found in L. plantarum C11 were
      identified in the isolates. The number of genes that were detected varied between
      the strains. The L. fermentum isolate EC11 also contained the plnDEFG genes. PCR
      amplification of DNA from isolates with primers directed to the upstream and
      downstream region of the plantaricin cluster generated an amplicon identical to
      that obtained with DNA from the control strain L. plantarum WCFS1. Amplification
      products from the positive strains were used for restriction analysis with
      HindIII, EcoRI and KpnI in separate reactions. Cluster analysis of restriction
      profiles revealed high similarities for EcoRI and HindII digest profiles, and an
      identical profile for all KpnI digests. The L. fermentum EC11 isolate clustered
      with L. plantarum strains in a group with a high correlation coefficient. The
      results suggest a low degree of diversity in the plantarincin gene cluster.
      However, other strains that tested positive for individual plantaricin genes may
      present great heterogeneity in the plantaricin operons. Because of their broad
      spectra of inhibition (including Escherichia coli, Salmonella enterica,
      Enterobacter aerogenes, Bacillus cereus, Staphylococcus aureus, Listeria
      monocytogenes, and Enterococcus faecalis), isolates from the present study could
      be used to improve the safety and storage stability of poto poto.

PMID- 18620773
TI  - Surgical resection vs. percutaneous ablation for hepatocellular carcinoma: a
      preliminary report of the Japanese nationwide survey.
AB  - BACKGROUND/AIMS: The treatment of choice for HCC remains controversial. We
      evaluated the therapeutic impact of surgical resection, PEI, and RFA for HCC on
      outcomes. METHODS: A database derived from a Japanese nationwide survey of 17,149
      patients with HCC treated by resection, PEI, or RFA between 2000 and 2003 was
      used to identify 7185 patients with no more than 3 tumors (< or = 3 cm) and a
      liver function of Child-Pugh class A or B. The patients classified into either a
      resection (n=2857), RFA (n=3022), or PEI group (n=1306) and their long-term
      outcomes were compared. RESULTS: The median follow-up period was 10.4 months. The
      2-year time-to-recurrence rate was 35.5%, 55.4%, and 73.3% in the resection, RFA,
      and PEI groups, respectively, while the number of recurrences was 2410, 2368, and
      862. Although the number of deaths was 55 (1.9%), 49 (1.6%), and 39 (3.0%), the
      overall survival rates were not different. In a multivariate analysis, surgical
      resection was a significant negative factor for recurrence as compared with RFA
      (relative risk, 0.62 [95% confidence interval, 0.54-0.71], P<0.0001) and PEI
      (0.45 [0.38-0.52], P<0.0001). CONCLUSIONS: This preliminary report suggested that
      surgical resection may provide less time-to-recurrence rate than either RFA or
      PEI in patients with HCC.

PMID- 18620774
TI  - Fish oil fed prior to ethanol administration prevents acute ethanol-induced fatty
      liver in mice.
AB  - BACKGROUND/AIMS: We examined whether dietary fish oil can prevent acute ethanol
      (alcohol)-induced fatty liver. METHODS: Mice were fed safflower oil, fish oil, or
      safflower oil plus a PPAR alpha activator on the day prior to ethanol
      administration. Oil red O staining, serum analysis, and RT-PCR were used to
      analyze ethanol-induced fatty liver. RESULTS: In mice fed safflower oil, ethanol
      increased liver TG 3-fold, with activation of SREBP-1c and ChREBP, which promote
      de novo lipogenesis, and increases in expression of mRNAs for PPAR gamma and
      DGATs mRNAs, which promote TG synthesis. When mice were fed fish oil, ethanol
      induced fatty liver was reduced by 73%. Fish oil decreased SREBP-1c activity and
      increased PPAR alpha activity. However, levels of DGAT1, DGAT2, ChREBP, LPK, and
      PPAR gamma mRNAs were increased in response to ethanol in mice fed fish oil.
      Prior administration of Wy14643, PPAR alpha activator, did not inhibit ethanol
      induced fatty liver, suggesting that PPAR alpha played little role in prevention
      of ethanol-induced fatty liver by fish oil. CONCLUSIONS: A single dose of ethanol
      increases the liver TG level via several mechanisms; however, prior ingestion of
      fish oil effectively prevents ethanol-induced fatty liver, at least in part, by
      decreasing basal SREBP-1c activity, especially a marked reduction in SCD1.

PMID- 18620775
TI  - Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic
      fatty liver disease.
AB  - BACKGROUND/AIMS: Citrin deficiency caused by SLC25A13 gene mutations develops
      into adult-onset type II citrullinemia (CTLN2) and may be accompanied with
      hepatic steatosis and steatohepatitis. As its clinical features remain unclear,
      we aimed to explore the characteristics of fatty liver disease associated with
      citrin deficiency. METHODS: The prevalence of hepatic steatosis in 19 CTLN2
      patients was examined, and clinical features were compared with those of non
      alcoholic fatty liver disease (NAFLD) patients without known SLC25A13 gene
      mutations. RESULTS: Seventeen (89%) CTLN2 patients had steatosis, and 4 (21%) had
      been diagnosed as having NAFLD before appearance of neuropsychological symptoms.
      One patient had steatohepatitis. Citrin deficiency-associated fatty livers showed
      a considerably lower prevalence of accompanying obesity and metabolic syndrome,
      higher prevalence of history of pancreatitis, and higher serum levels of
      pancreatic secretory trypsin inhibitor (PSTI) than fatty livers without the
      mutations. Receiver operating characteristic curve analyses revealed that a body
      mass index < 20kg/m(2) and serum PSTI>29ng/mL were associated with citrin
      deficiency. CONCLUSIONS: Patients presenting with non-alcoholic fatty liver
      unrelated to obesity and metabolic syndrome might have citrin deficiency, and
      serum PSTI may be a useful indicator for distinguishing this from conventional
      NAFLD.

PMID- 18620776
TI  - Patients with chronic hepatitis C achieving a sustained virological response to
      peginterferon and ribavirin therapy recover from impaired hepcidin secretion.
AB  - BACKGROUND/AIMS: The aim of this study is to determine the clinical relevance of
      hepatic producing iron regulatory hormone-hepcidin, on iron overload in patients
      with chronic hepatitis C (CHC). METHODS: Serum hepcidin was measured in 73 CHC
      patients by surface-enhanced laser desorption/ionization time of flight mass
      spectrometry (SELDI-TOF-MS), and compared to those of healthy controls and anemia
      of inflammation patients, and analyzed their relationship to hepatic hepcidin
      mRNA expression levels and clinical, hematological, and histological findings.
      The sequential changes of hepcidin were investigated in 27 CHC patients treated
      with a 48 week-course of pegylated-interferon (PEG-IFN) plus ribavirin therapy.
      RESULTS: Serum hepcidin was positively correlated with hepatic hepcidin mRNA
      levels, serum ferritin and the degree of hepatic iron deposition in CHC. Serum
      hepcidin-to-ferritin ratios were significantly lower in HCV positive patients
      than in HCV negative controls in both hyper- and normal-ferritinemic conditions.
      This relative impairment of hepcidin production was fully reversible after
      successful HCV eradication by PEG-IFN plus ribavirin, concomitantly with the
      improvement of the iron overload condition. CONCLUSIONS: The impairment of
      hepatic hepcidin production occurring with chronic HCV infection may enhance iron
      toxicity and lead to disease progression, and modulation or supplementation of
      hepcidin may be beneficial for these conditions in CHC.

PMID- 18620778
TI  - Saving maternal lives in resource-poor settings: facing reality.
AB  - OBJECTIVE: Evaluate safe-motherhood interventions suitable for resource-poor
      settings that can be implemented with current resources. METHODS: Literature
      review to identify interventions that require minimal treatment/infrastructure
      and are not dependent on skilled providers. Simulations were run to assess the
      potential number of maternal lives that could be saved through intervention
      implementation according to potential program impact. Regional and country level
      estimates are provided as examples of settings that would most benefit from
      proposed interventions. RESULTS: Three interventions were identified: (i) improve
      access to contraception; (ii) increase efforts to reduce deaths from unsafe
      abortion; and (iii) increase access to misoprostol to control postpartum
      hemorrhage (including for home births). The combined effect of postpartum
      hemorrhage and unsafe abortion prevention would result in the greatest gains in
      maternal deaths averted. DISCUSSION/CONCLUSIONS: Bold new initiatives are needed
      to achieve the Millennium Development Goal of reducing maternal mortality by
      three-quarters. Ninety-nine percent of maternal deaths occur in developing
      countries and the majority of these women deliver alone, or with a traditional
      birth attendant. It is time for maternal health program planners to reprioritize
      interventions in the face of human and financial resource constraints. The three
      proposed interventions address the largest part of the maternal health burden.

PMID- 18620779
TI  - Inoperable Pancoast tumors treated with hyperthermia-inclusive multimodality
      therapies.
AB  - PURPOSE: This study aimed to assess the feasibility, efficacy and complication of
      hyperthermia-inclusive multimodality therapies for patient with inoperable
      Pancoast tumor. MATERIAL AND METHODS: Five patients with inoperable Pancoast
      tumor were treated with hyperthermia-inclusive multimodality therapies. They
      received thermoradiotherapy with/without chemotherapy. Radiation therapy was
      delivered using 10 MV X-rays with total dose of 68-70 Gy. In the latter half of
      the radiation therapy hyperthermia was performed for 2-4 sessions once a week
      with 8 MHz radiofrequency device. RESULTS: For primary response, 4 tumors showed
      partial response to the treatment with the exception of 1 tumor who showed stable
      disease. Only one patient was with a short follow-up period (9 months), all other
      patients survived 3 years or more without recurrence. Of them, 2 patients were
      recognized with local recurrence at 38.7 and 42.7 months after treatment and died
      at 66.9 and 78.5 months after treatment. The other 2 patients are disease-free
      survivor for 4 and 5 years after treatment. No severe non-hematological toxicity
      was observed in each patient. CONCLUSION: These data suggested that hyperthermia
      inclusive multimodality therapies might be a promising approach for inoperable
      Pancoast tumor.

PMID- 18620780
TI  - Tumor expression of S100A6 correlates with survival of patients with stage I non
      small-cell lung cancer.
AB  - BACKGROUND: In a previously published in vitro study based on top-down proteomics
      we found that the calcium-binding proteins S100A6 and S100A4 were affected by
      exposure to ionizing radiation in a p53-dependent fashion. Both proteins showed
      post-translational modification changes, and S100A6 also showed increased
      expression and translocation in response to irradiation. Aim of the present study
      was to evaluate the expression of S100A6 and S100A4 in non-small-cell lung cancer
      (NSCLC). METHODS: S100A6 expression on archival tumor cell lysates from 39
      patients with radically resected NSCLC was assessed with SELDI-TOF-MS. S100A6
      identity was confirmed using a SELDI-based antibody-capture method on lysates
      from the A549 lung cancer cell line, cell lysates from two freshly prepared NSCLC
      samples, four plasma samples and one pleural effusion sample. Immunostainings for
      S100A6, S100A4 and p53 were performed on tissue microarrays containing 103 stage
      I surgically resected NSCLC cases and 14 normal lung parenchyma specimens.
      RESULTS: The presence of post-translationally modified S100A6 forms was confirmed
      with SELDI-MS on enriched tumor cell lysates, as well as in plasma and pleural
      effusion samples. In addition, high S100A6 peak intensity was associated with
      longer median survival (35 months vs. 18 months for high and low peak intensity,
      respectively; p=n.s.). The immunohistochemical analysis showed that 25% of tumors
      were S100A6 positive. S100A6 expression correlated directly with non-squamous
      histology (p<0.0001) and S100A4 expression (p=0.005), and inversely with p53
      expression (p=0.01). S100A6-positive cases showed a trend of longer survival
      compared with S100A6-negative cases (p=0.07). This difference became significant
      when the analysis was restricted to p53-negative cases (n=72). In this subgroup
      of patients, whose tumors likely exhibit a functional p53, S100A6 was an
      independent prognostic factor of improved survival at multivariate analysis (HR
      0.49, 95% CI 0.27-0.81, p=0.017). CONCLUSIONS: In this study we have validated on
      clinical material our previous findings on cell lines in terms of S100A6
      expression and post-translational modifications pattern in NSCLC. Moreover, the
      survival results obtained in p53-negative stage I NSCLC cases support the
      proposed pro-apoptotic function of S100A6 and suggest the hypothesis of a cross
      regulation between these two proteins.

PMID- 18620781
TI  - DLX5 overexpression impairs osteogenic differentiation of human bone marrow
      stromal cells.
AB  - The transcription factor DLX5 belongs to a family of homeoproteins required for
      craniofacial morphogenesis and forebrain development. DLX5 is expressed during
      formation of several skeletal elements such as cartilage, teeth and bone, and its
      knockout causes severe craniofacial malformations with a delay in the
      ossification process. Bone marrow contains mesenchymal progenitor cells which may
      differentiate along multiple pathways, therefore representing an interesting in
      vitro and in vivo model to study the mesodermal lineage differentiation. Here we
      report the effect of DLX5 overexpression in ex vivo expanded human bone marrow
      stromal cells by retroviral infection on the osteogenic lineage differentiation.
      A reduced mineral deposition was observed in DLX5-transduced cells upon
      osteogenic induction in culture. When DLX5-transduced cells were implanted in
      immunodeficient mice, a 60% reduction in bone matrix deposition was observed,
      whereas the in vitro chondrogenic potential was unaffected. A quantitative gene
      expression study indicated that DLX5 overexpression does not affect the early
      osteogenic commitment of bone marrow stromal cells but prevents their terminal
      differentiation. This block may be mediated by the observed persistent expression
      of SOX2, a transcription factor known to inhibit osteogenic differentiation.

PMID- 18620777
TI  - The JNK inhibitor SP600129 enhances apoptosis of HCC cells induced by the tumor
      suppressor WWOX.
AB  - BACKGROUND/AIMS: The FRA16D fragile site gene WWOX is a tumor suppressor that
      participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1
      interacts with WWOX and inhibits apoptosis. We investigated the function of WWOX
      in human hepatocellular carcinoma (HCC) and the effect of JNK inhibition on WWOX
      mediated apoptosis. METHODS: Allelic imbalance on chromosome 16 was analyzed in
      73 HCCs using 53 microsatellite markers. WWOX mRNA in HCC cell lines and primary
      HCCs was measured by real-time RT-PCR. Effects of WWOX on proliferation and
      apoptosis and the interaction between WWOX and JNK inhibition were examined.
      RESULTS: Loss on chromosome 16 occurred in 34 of 73 HCCs. Of 11 HCC cell lines, 2
      had low, 7 intermediate, and 2 had high WWOX mRNA. Of 51 primary tumors, 23 had
      low WWOX mRNA. Forced expression of WWOX in SNU387 cells decreased FGF2-mediated
      proliferation and enhanced apoptosis induced by staurosporine and the JNK
      inhibitor SP600129. Conversely, knockdown of WWOX in SNU449 cells using shRNA
      targeting WWOX increased proliferation and resistance to SP600129-induced
      apoptosis. CONCLUSIONS: WWOX induces apoptosis and inhibits human HCC cell growth
      through a mechanism enhanced by JNK inhibition.

PMID- 18620782
TI  - Omega-3 polyunsaturated fatty acids increase the neurite outgrowth of rat sensory
      neurones throughout development and in aged animals.
AB  - Polyunsaturated fatty acids (PUFA) of the omega-3 series and omega-6 series
      modulate neurite outgrowth in immature neurones. However, it has not been
      determined if their neurotrophic effects persist in adult and aged tissue. We
      prepared cultures of primary sensory neurones from male and female rat dorsal
      root ganglia (DRG), isolated at different ages: post-natal day 3 (P3) and day 9
      (P9), adult (2-4 months) and aged (18-20 months). Cultures were incubated with
      the omega-6 PUFA arachidonic acid (AA) and the omega-3 PUFA eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA), at 0.8, 4, 8 and 40muM. PUFA increased
      neurite outgrowth throughout the developmental stages studied. The effects of
      omega-3 PUFA, in particular DHA, were still prominent in aged tissue. The
      amplitude of the effects was comparable to that of nerve growth factor (NGF;
      50ng/ml) and all-trans-retinoic acid (ATRA; 0.1muM). The effects of PUFA were
      similar in cells positive or negative for the N52 neurofilament marker. Our
      results show that omega-3 PUFA have a marked neurite-promoting potential in
      neurones from adult and aged animals.

PMID- 18620783
TI  - Synaptic strength and postsynaptically silent synapses through advanced aging in
      rat hippocampal CA1 pyramidal neurons.
AB  - Synaptic dysfunction is thought to contribute to age-related learning
      impairments. Detailed information regarding the presence of silent synapses and
      the strength of functional ones through advanced aging, however, is lacking. Here
      we used paired-pulse minimal stimulation techniques in CA1 stratum radiatum to
      determine whether the amplitude of spontaneous and evoked miniature excitatory
      postsynaptic currents (sEPSCs and eEPSCs, respectively) changes over the lifespan
      of rats in hippocampal CA1 pyramidal neurons, and whether silent synapses are
      present in adult and aged rats. The amplitudes of both sEPSCs and eEPSCs at
      resting membrane potential (i.e., clamped at -65 mV) initially increased between
      2 weeks and 3 months, but then remained constant through 36 months of age. The
      potency of the eEPSCs at depolarized membrane potentials (i.e., clamped at +40
      mV), however, was highest among 36-month old rats. Additionally, presynaptically
      silent synapses in CA1 stratum radiatum disappeared between 2 weeks and 3 months,
      but postsynaptically silent synapses were present through advanced aging. The
      similarity of silent and functional synapses in CA1 hippocampus at resting
      membrane potentials throughout adulthood in rats may indicate that impairments in
      the mechanisms of synaptic plasticity and its subsequent stabilization, rather
      than deficient synaptic transmission, underlie age-related cognitive decline.
      Such a notion is consistent with the increased amplitude of synaptic currents at
      depolarized potentials, perhaps suggesting an upregulation in the expression of
      synaptic NMDA receptors once rats reach advanced age.

PMID- 18620784
TI  - Withania somnifera provides cardioprotection and attenuates ischemia-reperfusion
      induced apoptosis.
AB  - BACKGROUND & AIMS: The present study was undertaken to evaluate the
      cardioprotective mechanisms of Withania somnifera (Ws), in the setting of
      ischemia and reperfusion (IR) injury. METHODS: Wistar rats were divided into
      three groups and received orally saline (sham, control IR) and Ws-50 mg/kg (Ws
      IR), respectively, for 1 month. On the 31st day, in the rats of control IR and Ws
      IR group, LAD coronary artery occlusion was undertaken for 45 min followed by 1 h
      reperfusion. Subsequently, all the animals were sacrificed for biochemical,
      immunohistochemical {Bax and Bcl-2 protein}, terminal deoxynucleotidyl
      transferase biotin-dUTP nick end labeling (TUNEL) positivity and
      histopathological studies. RESULTS: Post-ischemic reperfusion injury resulted in
      significant cardiac necrosis, apoptosis, decline in antioxidant status and
      elevation in lipid peroxidation in the IR control group as compared to sham. Ws
      prior-treatment favorably restored the myocardial oxidant-antioxidant balance,
      exerted marked anti-apoptotic effects {upregulated Bcl-2 (p<0.001) protein,
      decreased Bax (p<0.01) protein, and attenuated TUNEL positivity (p<0.01)}, and
      reduced myocardial damage as evidenced by histopathologic evaluation.
      CONCLUSIONS: The antioxidant and anti-apoptotic properties of Ws may contribute
      to the cardioprotective effects.

PMID- 18620785
TI  - Salivary gland tumors: a single institution experience in India.
AB  - Between 1991 and 2006, 684 cases of salivary gland tumours were analysed
      retrospectively, of which 422 (62%) were benign and 262 (38%) malignant. Sixty
      one percent of tumours were in the parotid gland, 22% in the minor salivary
      glands, and 17% in the submandibular glands. The most common benign tumour was
      pleomorphic adenoma (86%), and the most common malignant tumours were adenoid
      cystic carcinoma (25%) and mucoepidermoid carcinoma (18%). Among the minor
      salivary gland tumours, most were seen in the palate (68%). We analyse the
      incidence and distribution of all types of salivary gland tumours in an Indian
      series, and provide data for comparison with other epidemiological studies from
      different geographical sites and races. Demographic data from these studies
      should help us to a better understanding of the biological and clinical
      characteristics of the disease.

PMID- 18620786
TI  - Recent developments in the treatment of aggressive non-Hodgkin lymphoma.
AB  - SUMMARY: Options for treating aggressive non-Hodgkin lymphoma (NHL) have expanded
      in recent years. In phase 3 clinical trials, giving rituximab with
      cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) every 3 weeks
      (R-CHOP-21) has been associated with improved survival, without increased
      toxicity, in all patient groups studied. Giving dose-dense CHOP--CHOP every 2
      weeks (CHOP-14)--has also proved appropriate for all patients 18-75 years old.
      Studies combining these approaches--dose-dense CHOP with rituximab (R-CHOP-14)-
      have shown improved survival over CHOP-14 in patients 60-81 years old. These
      results also indicate the importance of delivering chemotherapy at full dose and
      on schedule, which can improve survival in aggressive NHL. Effective delivery of
      dose-dense regimens requires granulocyte colony-stimulating factor support, which
      should also be considered for standard CHOP. A key question for the future is
      whether R-CHOP-14 is superior to R-CHOP-21.

PMID- 18620787
TI  - Bioremediation of oil-contaminated soil using Candida catenulata and food waste.
AB  - Even though petroleum-degrading microorganisms are widely distributed in soil and
      water, they may not be present in sufficient numbers to achieve contaminant
      remediation. In such cases, it may be useful to inoculate the polluted area with
      highly effective petroleum-degrading microbial strains to augment the exiting
      ones. In order to identify a microbial strain for bioaugmentation of oil
      contaminated soil, we isolated a microbial strain with high emulsification and
      petroleum hydrocarbon degradation efficiency of diesel fuel in culture. The
      efficacy of the isolated microbial strain, identified as Candida catenulata CM1,
      was further evaluated during composting of a mixture containing 23% food waste
      and 77% diesel-contaminated soil including 2% (w/w) diesel. After 13 days of
      composting, 84% of the initial petroleum hydrocarbon was degraded in composting
      mixes containing a powdered form of CM1 (CM1-solid), compared with 48% of removal
      ratio in control reactor without inoculum. This finding suggests that CM1 is a
      viable microbial strain for bioremediation of oil-contaminated soil with food
      waste through composting processes.

PMID- 18620788
TI  - Toxicity of water and sediment from stormwater retarding basins to Hydra
      hexactinella.
AB  - Hydra hexactinella was used to assess the toxicity of stormwater and sediment
      samples from three retarding basins in Melbourne, Australia, using an acute test,
      a sublethal test, and a pulse test. Stormwater from the Avoca St retarding basins
      resulted in a LC50 of 613 ml/L, NOEC and LOEC values of 50 ml/L and 100 ml/L,
      while the 7h pulse exposure caused a significant increase in the mean population
      growth rate compared to the control. Water samples from the two other retarding
      basins were found non-toxic to H. hexactinella. This is the first study to employ
      sediment tests with Hydra spp. on stormwater sediments and a lower population
      growth rate was observed for organisms exposed to sediment from the Avoca St
      retarding basins. The behavioral study showed that H. hexactinella tended to
      avoid the sediment-water interface when exposed to sediment from all retarding
      basins, compared to the reference sediment. Further work is needed to determine
      the long-term effects of stormwater polluted sediments and acute effects due to
      organism exposure to short-term high concentrations during rain events.

PMID- 18620789
TI  - Brain activation and deactivation during location and color working memory tasks
      in 11-13-year-old children.
AB  - Using functional magnetic resonance imaging (fMRI) and n-back tasks we
      investigated whether, in 11-13-year-old children, spatial (location) and
      nonspatial (color) information is differentially processed during visual
      attention (0-back) and working memory (WM) (2-back) tasks and whether such
      cognitive task performance, compared to a resting state, results in regional
      deactivation. The location 0-back task, compared to the color 0-back task,
      activated segregated areas in the frontal, parietal and occipital cortices
      whereas no differentially activated voxels were obtained when location and color
      2-back tasks were directly contrasted. Several midline cortical areas were less
      active during 0- and 2-back task performance than resting state. The task-induced
      deactivation increased with task difficulty as demonstrated by larger
      deactivation during 2-back than 0-back tasks. The results suggest that, in 11-13
      year-old children, the visual attentional network is differently recruited by
      spatial and nonspatial information processing, but the functional organization of
      cortical activation in WM in this age group is not based on the type of
      information processed. Furthermore, 11-13-year-old children exhibited a similar
      pattern of cortical deactivation that has been reported in adults during
      cognitive task performance compared to a resting state.

PMID- 18620790
TI  - Investigation of acute effects of aflatoxin on rat proximal and distal colon
      spontaneous contractions.
AB  - Aflatoxins are one of the most potent toxic, mutagenic, teratogenic,
      cancerogenic, and immunosuppresive substances that naturally occurring
      contaminants of food. There are some studies in various animal species that have
      reported aflatoxin effects on gastrointestinal systems, but acute effects of
      aflatoxins have not been clearly investigated. In this study, we aimed to
      investigate the acute gastrointestinal effects of total aflatoxin on rat isolated
      proximal and distal colon. Aflatoxin was given cumulatively at 10(-8)-10(-5)M
      concentrations and the amplitude and frequency of proximal and distal colon
      contractions were increased significantly. In the presence of atropine sulfate
      (23.6 nM) and morphine (0.3 microM) the amplitude and frequency of aflatoxin
      induced spontan contractions in the proximal and distal colon decreased
      significantly, on the other hand, L-NNA (0.3 microM) increased contractions'
      amplitude and frequency significantly in the proximal colon but not in the distal
      colon. In conclusion, aflatoxin may increase the amplitude and frequency of
      contractions by increasing muscarinic activity or by decreasing NO synthase
      and/or release in proximal colon and by increasing muscarinic activity in the
      distal colon. These findings of aflatoxin on isolated rat proximal and distal
      colon may explain their acute gastrointestinal effects in humans and animals.

PMID- 18620791
TI  - Evaluation of bond strength of various margin ceramics to a zirconia ceramic.
AB  - OBJECTIVE: This study evaluated the bond strengths of four different margin
      ceramics based on fluoroapatite and feldspath to a zirconia ceramic. METHODS:
      Zirconia cores (Zirconzahn) (N=28, n=7/margin ceramic group) were fabricated
      according to the manufacturers' instructions (diameter: 4mm; thickness: 2mm) and
      ultrasonically cleaned. Four different margin ceramics (thickness: 5mm) (Cerabien
      Zr, Noritake; Ceramco PFZ, Ceramco; e.max, Ivoclar Vivadent and Triceram,
      Dentaurum) were vibrated and condensed in a stainless steel mould and fired onto
      their zirconia cores. After trying the specimens in the mould for minor
      adjustments, they were again ultrasonically cleaned and embedded in PMMA. The
      specimens were stored in distilled water at 37 degrees C for 1 week and shear
      bond strength (MPa+/-S.D.) tests were performed in a universal testing machine
      (crosshead speed: 0.5mm/min). Failure modes were recorded under SEM. RESULTS:
      Significant effect of margin ceramic types were found on the bond strength values
      (P<0.05). The mean bond strength values of Ceramco margin ceramic to zirconia was
      significantly lower (25.4+/-4.5 MPa) (P<0.05) than those of Cerabien (31.6+/-6.4
      MPa), e.max (35.9+/-8.4 MPa), and Triceram margin ceramic (38.8+/-7.1 MPa)
      systems. CONCLUSIONS: Margin ceramics, compatible with zirconia framework
      material tested in the present study, exhibited high bond strength values.
      Variations in thermal expansion coefficients might influence their bond strength
      values.

PMID- 18620793
TI  - Increasing CPR duration prior to first defibrillation does not improve return of
      spontaneous circulation or survival in a swine model of prolonged ventricular
      fibrillation.
AB  - INTRODUCTION: The optimum duration of cardiopulmonary resuscitation (CPR) prior
      to first rescue shock is unknown. Clinical trials have used 90 and 180 s. Neither
      of these durations may be optimal. We sought to determine the optimum duration of
      CPR prior to first defibrillation attempt and whether this varied depending on
      the duration of ventricular fibrillation (VF). In this porcine model of basic
      life support, our outcomes were rates of return of spontaneous circulation
      (ROSC), survival, and coronary perfusion pressure (CPP). METHODS: We anesthetized
      and instrumented 45 swine and then induced VF. After 5 or 8 min of untreated VF,
      we randomized the swine to mechanical CPR for 90, 180, or 300 s. A single rescue
      shock (150 J biphasic) was then administered. If this shock failed, 2 min of
      mechanical CPR were completed prior to the next rescue shock. CPP was calculated
      for each 30s epoch. ROSC was defined as a blood pressure >80 mmHg sustained for
      60s. Survival was defined as sustained ROSC for 20 min. Data were analyzed with
      descriptive statistics, Fisher's exact test, and ANOVA. RESULTS: In the 5 min VF
      cohort, the rate of ROSC did not differ between the three groups (90 s: 25%; 180
      s: 38%; 300 s: 38%, p>.05). Survival rates did not differ (90 s: 25%; 180 s: 25%;
      300 s: 25%, p>0.05). In the 8 min VF cohort, no animals experienced ROSC or
      survival. CPP were calculated by 30s epoch and did not differ between the three
      groups (p>0.05). CPPs decline after 180 s of CPR. CONCLUSIONS: ROSC and survival
      were equivalent regardless of VF duration and CPR duration. When CPR begins late,
      CPPs are low, stressing the importance of early CPR. We do not recommend 300 s of
      CPR unless a defibrillator is unavailable.

PMID- 18620794
TI  - A review, and performance evaluation, of single-parameter "track and trigger"
      systems.
AB  - OBJECTIVES: There is no up-to-date literature review of physiologically-based,
      single-parameter weighted "track and trigger" systems (SPTTS) and little data on
      their sensitivity and specificity to predict adverse outcomes. The aim of this
      study was to describe the SPTTS in clinical use and measure their sensitivity and
      specificity when using admission vital signs data for predicting in-hospital
      mortality. MATERIALS AND METHODS: We performed a systematic review of the
      literature to describe the SPTTS, their components and their differences. We
      measured their sensitivity and specificity for predicting in-hospital mortality
      when using a database of 9987 admission vital signs datasets. RESULTS: We
      identified 39 unique classes of SPTTS, of which 30 were evaluated. There was
      considerable variation in the physiological variables used, together with
      significant variation in the physiological values used to trigger a medical
      emergency or critical care outreach team. There was marked variation in
      sensitivity (7.3-52.8%), specificity (69.1-98.1%), positive predictive values
      (13.5-26.1%), negative predictive values (92.1-94.2%) and the potential number of
      calls triggered (234-3271). CONCLUSIONS: There is a wide range of unique, but
      very similar, SPTTS in clinical use. Although specificities were high,
      sensitivities were too low to provide institutions with confidence that these
      SPTTS could identify patients at risk of in-hospital death using admission vital
      signs. Institutions may wish to consider these data when selecting which, if any,
      single-parameter track and trigger systems to introduce.

PMID- 18620795
TI  - Therapeutic hypothermia after out-of-hospital cardiac arrest due to Brugada
      syndrome.
AB  - A 56-year-old man was admitted to our hospital after successful resuscitation for
      out-of-hospital cardiac arrest. Electrocardiogram on admission showed right
      bundle branch block and ST segment elevation in leads V1-3. Subsequent
      intravenous infusion of isoproterenol rapidly resolved ST segment elevation,
      suggesting Brugada syndrome. Therapeutic hypothermia, that was performed with a
      target temperature of 34.0 degrees C did not induce ST segment elevation in leads
      V1-3. The J-ST segment elevation rather became much more normal, suggesting a
      beneficial effect of mild therapeutic hypothermia. Serial ECG showed the temporal
      variation of ST segment elevation, and pilsicainide challenge test showed the
      occurrence of ST segment elevation, confirming the diagnosis of Brugada syndrome.
      Clinical observation suggested that mild therapeutic hypothermia reversed the
      Brugada phenotype through the prevention of fever as well as being indicated for
      cerebral protection after cardiac arrest. In conclusion, therapeutic hypothermia
      with a temperature of 34.0 degrees C can be used safely in Brugada syndrome.

PMID- 18620796
TI  - Regulation of alloimmune responses by dendritic cell subsets.
AB  - OBJECTIVE: Dendritic cells (DCs) are powerful mediators of immune responses. We
      have demonstrated that the content of plasmacytoid (type 2) dendritic cells (DC2)
      within allogeneic bone marrow grafts impacts survival and graft-vs-host disease
      following transplantation. In order to better understand the effect of DC subsets
      on regulation of immunity, we tested the effect of DC subsets on T cells in a
      model of indirect antigen presentation to mimic presentation of host-type
      alloantigen by donor-type DC. MATERIALS AND METHODS: Volunteers underwent
      apheresis without cytokine priming, and DC1, DC2, naive, and memory T cells were
      purified by immunomagnetic bead and fluorescein-activated cell sorting. Purified
      DC1 and DC2 cells were cultured with third-party irradiated blood mononuclear
      cells and either naive or memory homologous T cells in mixed lymphocyte
      reactions. RESULTS: Myeloid (type 1) dendritic cells (DC1) induced significant
      proliferation of homologous T cells and were more effective in priming naive T
      cell responses than memory T cells responding to alloantigen. DC2 cells induced
      minimal T-cell proliferation regardless of the T-cell subset used as the
      responding fraction. Secondary mixed lymphocyte reaction studies demonstrated
      that DC2 primed T cells remained hyporesponsive even when challenged with a third
      party alloantigen. The immunostimulatory effect of DC1 required DC-to-T-cell
      contact, and induced interleukin-12 secretion, while DC2 cells induced interferon
      gamma secretion. Polymerase chain reaction analysis of DC2-primed T cells
      demonstrated a significant increase in Foxp3 expression, supporting induction of
      a regulatory T-cell population. CONCLUSION: DC1 and DC2 cells induced divergent T
      cell responses using homologous cells. Better understanding of DC2-mediated T
      cell suppression may yield strategies that overcome tumor-specific immune
      tolerance and regulate graft-vs-host disease.

PMID- 18620797
TI  - VEGF signaling on hematopoietic precursors restricts B-lymphoid commitment in
      vitro and in vivo.
AB  - Vascular endothelial growth factor (VEGF) signals on vascular and hematopoietic
      cells via its receptors, VEGFR-2 (KDR) and VEGFR-1 (FLT-1). Elevated levels of
      VEGF, such as during tumor growth or inflammation, have been suggested to
      suppress hematopoiesis; most studies refer to KDR as the main receptor involved
      in this inhibitory effect. In the present study, having detected expression of
      FLT-1 in B-lymphoid precursors, we exploited the possibility that VEGF signaling
      via FLT-1 might affect early B-cell commitment. Using a well-established in vitro
      B-cell differentiation assay, we demonstrate that FLT-1 blockade promotes B-cell
      commitment and subsequent differentiation, while KDR blockade has no effect on B
      cell commitment. In agreement, in vivo transplantation of human (CD34+) or murine
      (Sca1+l/Lin-) FLT-1-negative hematopoietic precursors into irradiated severe
      combined immune-deficient mice restored the bone marrow lymphoid compartment,
      while transplanting the FLT-1-positive counterpart failed to repopulate the
      lymphoid compartment, and unexpectedly resulted in early death of the irradiated
      recipients due to hematopoietic suppression. Taken together, we suggest that VEGF
      signaling via FLT-1 on hematopoietic precursors may restrict lymphopoiesis.

PMID- 18620798
TI  - Ultrasound transmission velocity for noninvasive evaluation of jaw bone quality
      in vivo before dental implantation.
AB  - For the insertion of dental implants, mechanical bone properties at the
      implantation site have great impact both for therapeutic regimes as well as for
      the overall long-term success, making a reliable method for the preoperative
      assessment of the bone quality desirable. Ultrasound transmission velocity (UTV)
      has been introduced as a noninvasive method to analyze mechanical properties of
      bone. The aim of this study was the first intra-oral in vivo assessment of
      alveolar crest UTV values of edentulous jaws. Partly or fully edentulous patients
      (n = 108) were enrolled in this study, taking into account possible influence
      factors that affect bone quality (osteoporosis, radiation therapy). Six intra
      oral measurement points were used: left side region, right side region and
      frontal region, for upper and lower jaw, respectively. Ultrasound transmission
      velocity values were measured bicortically (in bucco-oral direction) and
      correlated to sex, age, measurement site and history of osteoporosis or radiation
      therapy. We found a minimum mouth opening of 30 mm, as well as a residual
      alveolar ridge height of 8 mm as thresholds for a reliable intra-oral placement
      of the device. Xerostomia was no contraindication. Assessment of intra-oral UTV
      showed significantly higher values both for mandibular side regions (female 1713
      +/- 153 m/s, male 1734 +/- 221 m/s) and the maxillary frontal region (female 1665
      +/- 189 m/s, male 1648 +/- 82 m/s) than for maxillary side regions (female 1538
      +/- 177 m/s, male 1583 +/- 90 m/s). These data were even more clarified by intra
      individual correlation of upper and lower jaw side region UTV values. We found no
      correlation between assessed UTV values and the variables sex, age, osteoporosis
      or radiation therapy. The use of a small UTV device in this study allowed the
      recording of intra-oral UTV values in a large and heterogeneous patient
      collective for the first time. Assessment of alveolar-ridge UTV might offer the
      possibility to identify critical bone quality before implantation or to monitor
      bone healing (mineralization) after augmentation procedures.

PMID- 18620799
TI  - Contrast sonography enables noninvasive and quantitative assessment of
      neovascularization after stem cell transplantation.
AB  - Stem cell transplantation is one of the attractive therapeutic strategies for the
      treatment of hindlimb ischemia. However, few studies have quantitatively assessed
      perfusion noninvasively in deep tissues after cell transplantation. In this
      study, we examined the feasibility of contrast sonography for the assessment of
      perfusion after bone marrow-derived mesenchymal stem cell (MSC) transplantation
      by using a rat unilateral hindlimb ischemia model. The quantitative parameters
      derived from contrast sonography were compared with the colored microspheres
      derived blood flow and the capillary density. Nine rats were assigned each to a
      control (saline injection) or a treated (MSC transplantation) group. Video
      intensity vs. pulsing interval plots were acquired with ultraharmonic imaging of
      SONOS5500 during IV infusion of Levovist. The left-to-right ratio of hindlimb
      blood volume (A-ratio), microbubble velocity (beta-ratio) and hindlimb blood flow
      (Abeta-ratio) were calculated. The MS-ratio, the ratio of the left to the right
      hindlimb blood flow determined using colored microspheres, was also calculated.
      Although A-ratio did not change, beta- and Abeta-ratio in the treated group were
      significantly higher than those in the control group. In addition, MS-ratio and
      capillary density in the treated group were significantly higher than those in
      the control group. Compared with A- and Abeta-ratio, beta-ratio had the highest
      correlation with MS-ratio and capillary density (vs. MS-ratio: r = 0.66, p <
      0.01; vs. capillary density: r = 0.52, p < 0.05). The results of our study imply
      that the contrast sonography-derived beta-ratio is a useful parameter that
      reflects the perfusion after cell transplantation in ischemic hindlimb.

PMID- 18620800
TI  - Estimation of the transverse strain tensor in the arterial wall using IVUS image
      registration.
AB  - Intravascular ultrasound (IVUS) elastography is an imaging technique that obtains
      the local mechanical properties of the artery wall and atherosclerotic plaques
      through strain measurements using IVUS. Knowledge of these mechanical properties
      may provide crucial information that can help in estimating plaque composition
      and its vulnerability. Here, we present a new method to estimate the transverse
      strain tensor of the arterial wall based on nonrigid image registration using
      IVUS images. This method registers a pair of images acquired at a vessel site
      under different levels of luminal pressure. The 2-D displacement field in the
      vessel cross-section is estimated from image registration; then the displacement
      field is used to calculate the 2-D local strain tensor. From the strain tensor,
      the strain in any direction in the cross-section can be obtained; here, the
      radial and circumferential strain distributions are presented. This strain
      estimation method has been validated with synthetic motion IVUS images and
      evaluated using the IVUS images of a polyvinyl alcohol cryogel phantom. The
      accuracy of the estimated strain and the ability of the method to overcome IVUS
      system noise are demonstrated.

PMID- 18620801
TI  - A double-blind randomized controlled trial of topiramate and amitriptyline either
      alone or in combination for the prevention of migraine.
AB  - OBJECTIVE: Effectiveness of antidepressants and antiepileptic drugs has already
      been demonstrated for migraine prophylaxis as monotherapy. In the present study,
      the efficacy and tolerability of amitriptyline and topiramate combination is
      examined in the prevention of migraine attacks, in comparison to the monotherapy
      of each drug. METHODS: A total of 73 patients with migraine headache with or
      without aura are included in this single-center, double-blind, randomized, and
      controlled trial. Patients were assigned to receive topiramate alone,
      amitriptyline alone or a combination of these drugs. Frequency, duration and
      severity of migraine attacks, accompanied symptoms, depressive state, consumption
      of medications, side effects and patient satisfaction were evaluated. RESULTS:
      All treatments resulted in significant improvements in all efficacy measures
      (p<0.001 for all comparisons). However, patients receiving combination treatment
      had higher patient satisfaction compared with other groups both at 8 and 12 weeks
      (p=0.006 and p<0.001, respectively). Patients receiving amitriptyline and
      combination treatments had better depression scores compared with the topiramate
      group. Combination group had fewer side effects with a less amount of
      amitriptyline consumption. CONCLUSION: Amitriptyline and topiramate combination
      may be beneficial for patients with migraine and comorbid depression,
      particularly in terms of side effects and associated displeasure due to
      monotherapy.

PMID- 18620802
TI  - Transcription factor AP2alpha (TFAP2a) regulates differentiation and
      proliferation of neuroblastoma cells.
AB  - Neuroblastoma, the most common extracranial solid tumour of childhood, is derived
      from neural crest progenitor cells. The TFAP2a transcription factor regulates
      neural crest patterning. We analysed TFAP2a protein expression in 97 primary
      neuroblastic tumors and report that TFAP2a was strongly expressed in poorly
      differentiated neuroblastomas. TFAP2a expression in tumor cells of differentiated
      neuroblastic tumors was below detection. TFAP2a was strongly expressed in 4 of 6
      neuroblastoma cell lines tested, and TFAP2a siRNA mediated knock down in SH-EP
      cells reduced proliferation and induced a more differentiated phenotype
      associated with an increase in the expression of the differentiation marker
      neurotensin.

PMID- 18620803
TI  - Comparison of atmospheric mercury (Hg) among Korea, Japan, China and Taiwan
      during 2000-2008.
AB  - The paper reviewed studies about total gaseous mercury, atmospheric particulate
      of mercury and average dry deposition fluxes of mercury in Korea, Japan, China
      and Taiwan. This study compared sample collection and analytical methods for
      mercury in Asian countries. Analytical results indicated that the primary mercury
      sources are anthropogenic source (for example coal burning) and high temperature
      processes. This study also elucidates the sources, analytical tools, and the
      average concentrations for atmospheric mercury (Hg) for these Asian countries
      during 2000-2008. This study indicated that the total gaseous mercury
      concentrations were higher in urban area than that in suburban area in Asian
      countries (Korea, Japan, China and Taiwan). As for the seasonal variations, in
      general, the average total gaseous mercury concentrations were higher in winter
      than that in summer especially in China. In addition, the average total gaseous
      mercury concentrations were higher in mining areas than that in the rest of the
      other areas. And the total gaseous mercury concentrations were decreasing as this
      distance increasing. These phenomena revealed that the total gaseous mercury
      concentrations are reduced by long-distance transportation especially in the main
      land of China.

PMID- 18620804
TI  - Kinetic and isotherm studies of Cu(II) biosorption onto valonia tannin resin.
AB  - The biosorption of Cu(II) from aqueous solutions by valonia tannin resin was
      investigated as a function of particle size, initial pH, contact time and initial
      metal ion concentration. The aim of this study was to understand the mechanisms
      that govern copper removal and find a suitable equilibrium isotherm and kinetic
      model for the copper removal in a batch reactor. The experimental isotherm data
      were analysed using the Langmuir, Freundlich and Temkin equations. The
      equilibrium data fit well in the Langmuir isotherm. The experimental data were
      analysed using four sorption kinetic models - the pseudo-first- and second-order
      equations, the Elovich and the intraparticle diffusion model equation - to
      determine the best fit equation for the biosorption of copper ions onto valonia
      tannin resin. Results show that the pseudo-second-order equation provides the
      best correlation for the biosorption process, whereas the Elovich equation also
      fits the experimental data well.

PMID- 18620805
TI  - Preparation and characterization of polyethyleneglycolmethacrylate (PEGMA)-co
      vinylimidazole (VI) microspheres to use in heavy metal removal.
AB  - Polyethyleneglycolmethacrylate (PEGMA) and vinylimidazole (VI) were used in order
      to obtain microspheres of PEGMA-VI copolymers that can be used in heavy metal
      removal applications. The obtained copolymers were characterized and their use as
      sorbents in heavy metal removal was investigated. In the first part of the study,
      PEGMA-VI microspheres were prepared by suspension polymerization method. The
      obtained swellable microspheres with 10-50 microm average diameter did not have
      permanent porosity according to the morphological and physicochemical
      determinations. The sizes of microspheres became smaller with increasing VI and
      cross-linker ethyleneglycoldimethacrylate (EGDMA) contents and increasing
      agitation rate. The VI content, EGDMA ratio, pH and ionic strength were
      determined as the effective parameters on the swelling behavior of PEGMA-VI
      microspheres. In the second part of the study, Cu(II) ions were used as a model
      species in order to investigate the usability of the obtained PEGMA-VI
      microspheres in heavy metal removal. Adsorption capacities under optimum
      conditions were determined. The Cu(II) ion adsorption capacity increased by
      increasing the initial Cu(II) ion concentration, and it reached the maximum value
      (i.e., 30 mg Cu(II)/g PEGMA-VI microspheres) at 400 mg Cu(II)/L initial Cu(II)
      ion concentration under the determined optimum conditions. Microspheres were
      found to be reusable after desorption for several times.

PMID- 18620806
TI  - TiO(2)/BaTiO(3)-assisted photocatalytic mineralization of diclofop-methyl on UV
      light irradiation in the presence of oxidizing agents.
AB  - Gas chromatograph-mass spectroscopic identification of intermediate products in
      the degradation of diclofop-methyl and the kinetics of the reaction has been
      investigated. Formation of 4-[(2,4-dichlorophenoxy) phenoxy] ethane and (2,4
      dichlorophenoxy) phenol was investigated. The other intermediate products are 2,4
      dichlorophenol, 2,4-dichlorobenzene, phenol and acetic acid have been
      ascertained. The decrease in the concentration of the parent/intermediate
      compounds is followed by UV-vis spectral study and the supportive information on
      the functional groups in the intermediates has been obtained from IR
      spectroscopy. Degradation process proceeds with oxidation-reduction reaction by
      the attack of OH*, H*, O(2)*(-) free radicals, which are photogenerated on the UV
      light illuminated TiO(2)/BaTiO(3) photocatalysts particles in aqueous medium. In
      this presentation another wide band gap semiconductor BaTiO(3) is shown to have
      comparable photocatalytic efficiency. The oxidizing agents are added to
      accelerate the rate of the reaction by enhancing the formation of free radicals.
      Based on the intermediates formed in the process of degradation, a suitable
      mechanism has been proposed.

PMID- 18620808
TI  - Chromium (VI) adsorption on boehmite.
AB  - Boehmite was synthesized and characterized in order to study the adsorption
      behavior and the removal of Cr(VI) ions from aqueous solutions as a function of
      contact time, initial pH solution, amount of adsorbent and initial metal ion
      concentration, using batch technique. Adsorption data of Cr(VI) on the boehmite
      were analyzed according to Freundlich, Langmuir and Dubinin-Radushkevich (D-R)
      adsorption models. Thermodynamic parameters for the adsorption system were
      determinated at 293, 303, 313 and 323K temperatures. The kinetic values and
      thermodynamic parameters from the adsorption process show that the Cr(VI) ions
      adsorption on boehmite is an endothermic and spontaneous process. These results
      show that the boehmite could be considered as a potential adsorbent for chromium
      ions in aqueous solutions.

PMID- 18620807
TI  - Bioavailability of heavy metals monitoring water, sediments and fish species from
      a polluted estuary.
AB  - Concentrations of heavy metals (Cu, Zn, Cd, Pb and As) were measured in water,
      sediment and two fish species, Sparus aurata and Solea senegalensis, from the
      estuary of Tinto and Odiel rivers in Huelva (Spain), one of the most metallic
      polluted estuaries in Europe. As a forward step to understand metal
      bioavailability and assess the potential impact on aquatic biota, a study of
      heavy metal speciation of sediments and water were achieved. High levels of total
      and dissolved Zn and Cu were found in water and high pollution of Zn, Pb, As and
      Cu were found in sediments. Availability of metals was established as following
      ranking: Cd>Zn>Cu>Pb in both water and sediment. In addition, the effect of this
      pollution was studied by evaluation of metal bioaccumulations and correlations
      obtained between metal levels in fractions of water and sediment and metal levels
      in fish tissues. High Cu and Zn levels were observed in liver tissue of both
      species, in according with higher total content and more available metals in
      water and sediment. Correlations among metal content in tissues and different
      fractions of metal in water for S. aurata and sediment for S. senegalensis were
      found.

PMID- 18620809
TI  - A preconcentration system for determination of copper and nickel in water and
      food samples employing flame atomic absorption spectrometry.
AB  - A separation/preconcentration procedure using solid phase extraction has been
      proposed for the flame atomic absorption spectrometric determination of copper
      and nickel at trace level in food samples. The solid phase is Dowex Optipore SD-2
      resin contained on a minicolumn, where analyte ions are sorbed as 5-methyl-4-(2
      thiazolylazo) resorcinol chelates. After elution using 1 mol L(-1) nitric acid
      solution, the analytes are determinate employing flame atomic absorption
      spectrometry. The optimization step was performed using a full two-level
      factorial design and the variables studied were: pH, reagent concentration (RC)
      and amount of resin on the column (AR). Under the experimental conditions
      established in the optimization step, the procedure allows the determination of
      copper and nickel with limit of detection of 1.03 and 1.90 microg L(-1),
      respectively and precision of 7 and 8%, for concentrations of copper and nickel
      of 200 microg L(-1). The effect of matrix ions was also evaluated. The accuracy
      was confirmed by analyzing of the followings certified reference materials: NIST
      SRM 1515 Apple leaves and GBW 07603 Aquatic and Terrestrial Biological Products.
      The developed method was successfully applied for the determination of copper and
      nickel in real samples including human hair, chicken meat, black tea and canned
      fish.

PMID- 18620810
TI  - Leaching behavior of pollutants in ferrochrome arc furnace dust and its
      stabilization/solidification using ferrous sulphate and Portland cement.
AB  - In this study, dissolution properties under different conditions and pollution
      potential by toxicity characteristic leaching procedure (TCLP) of arc furnace
      dust generated in the production of ferrochrome were examined and some
      stabilization/solidification (S/S) techniques were applied to the dust depending
      on contaminants determined. Dissolution properties and pollution potentials of
      all the materials stabilized/solidified were also studied under the similar
      conditions. It was determined that the metallic components concentrations
      dissolved from the ferrochrome arc furnace dust (FAFD) except for chromium and
      zinc were below the detection limits. The chromium concentration dissolved from
      the FAFD by TCLP was found to be 9.8 mg/l. Portland cement (PC), PC-FeSO(4) and
      PC-sand-FeSO(4) mixtures for S/S of the FAFD were tested. Although metal ions in
      the cationic form were stabilized when the PC was only used, Cr(VI) in the sample
      was not changed depending on PC amount and remained in the soluble chromate form.
      The stabilization efficiency of Cr(VI) increased by the increasing amounts of PC
      and FeSO(4). The best S/S of the FAFD was accomplished when the 5 stoichiometric
      amounts of FeSO(4), 30% PC and 16% sand mixture were used. TCLP leaching results
      of the samples obtained under the optimum conditions were below the EPA
      landfilling limits.

PMID- 18620812
TI  - Towards better 3-D reconstructions by combining electron tomography and atom
      probe tomography.
AB  - Scanning transmission electron microscope tomography and atom-probe tomography
      are both three-dimensional techniques on the nanoscale. We demonstrate here the
      combination of the techniques by analyzing the very same volume of an Al-Ag alloy
      specimen. This comparison allows us to directly visualize the theoretically known
      artifacts of each technique experimentally, providing insight into the optimal
      parameters to use for reconstructions and assessing the quality of each
      reconstruction. The combination of the techniques for accurate morphology and
      compositional information in three dimensions at the nanoscale provides a route
      for a new level of materials characterization and understanding.

PMID- 18620813
TI  - Aspects of the life cycle of Amblyomma parvum (Acari: Ixodidae) under natural
      conditions.
AB  - Monthly samplings of the rodent Galea musteloides (Caviidae) were carried out
      from January 2005 to December 2006 in Quilino, Cordoba Province, Argentina, to
      determine the seasonal distribution of immature stages of Amblyomma parvum. In
      the same locality, cattle and goats were also monthly examined to asses the
      seasonality of the females of this species. Engorged ticks collected on their
      natural hosts were maintained in the laboratory at 25 degrees C and 83-86%
      relative humidity to study biological parameters, and groups of larvae and nymphs
      were also maintained at three different photoperiods [12h light (L)-12h dark (D),
      14 L-10 D, and 10 L-14 D]. Larvae were found from late summer to early winter
      with the peak in autumn, nymphs were collected from early winter to early spring
      with the peak in middle winter, and females were detected on cattle and goats
      during spring and summer, with the peak in early and middle summer. The pre-moult
      period of engorged immature ticks exposed at different photoperiods in the
      laboratory show no indication of morphogenetic diapause, being the maximum period
      16.4 days for larvae and 21.8 days for nymphs. The difference in the mean
      engorgement weight of nymphs moulting to females (6.2mg+/-1.8) and to males
      (2.1mg+/-0.1) was statistically significant (P<0.01), but the difference in the
      pre-moult period of the nymphs moulting to females (20.1 days+/-2.0) and to males
      (18 days+/-2.0) was not significant (P>0.01). The average weight of females was
      206.1mg+/-23.6, the mean number of eggs laid was 1500.4+/-298.2, the average of
      pre-oviposition period was 6.5 days+/-0.8, and the minimum incubation period of
      eggs was 33.1 days+/-1.2. There was not significant correlation between the
      weight of females and the pre-oviposition period and between weight of immature
      stages and pre-moult period, but there was significant positive correlation
      between weight of females and number of eggs laid. A. parvum has a life cycle
      under natural conditions with one generation per year characterized by distinct
      seasonal peaks of activity for each parasitic stage, where adults are abundant in
      the hottest months and the immature stages prevail in the dry season. Apparently,
      this life cycle is not regulated via diapause. Additional studies on the life
      cycle of A. parvum in nature should be performed in other countries to confirm
      the results obtained in Argentina.

PMID- 18620814
TI  - Re-evaluating the economics of neosporosis control.

PMID- 18620815
TI  - The role of doxorubicin and epirubicin in the treatment of patients with
      metastatic hormone-refractory prostate cancer.
AB  - Advanced hormone-refractory prostate cancer (HRPC) is characterized by
      prevalently osteoblastic bone metastases which are what mostly affect these
      patients' quality of life and make the assessment of response to treatment
      particularly difficult by commonly used criteria. HRPC cannot be cured by any
      available therapeutic option, and chemotherapy has to be still considered as a
      palliative treatment. The anthracyclines doxorubicin (Dox) and epirubicin (Epi),
      alone or in combination with other agents, have been extensively used in the
      treatment of HRPC, but controversial results have been reported. The majority of
      reviewed studies reported a pain reduction in >50% of patients receiving Dox or
      Epi, suggesting a substantial palliative effect by their use in metastatic HRPC.
      The weekly schedule of anthracyclines seemed to achieve similar results to the 3
      weekly schedule but with a better toxicity profile. Although the toxic adverse
      effects were usually manageable when anthracyclines were combined with other
      agents, toxicity was severe by a number of aggressive regimens. Docetaxel is
      today approved for the treatment of HRPC, and must be considered the standard
      platform on which new agents may be combined. Given that HRPC includes a
      heterogeneous group of patients with variable rates of tumour growth, the
      combination of docetaxel with active agents such as anthracyclines may deserve
      further clinical investigation.

PMID- 18620816
TI  - The effect of food deprivation on cigarette smoking in females.
AB  - Food deprivation is associated with increased self-administration of nicotine and
      other substances in laboratory animals, although little is known about the
      effects of food deprivation on substance use in humans. A within-subjects design
      was utilized to test the primary hypotheses that smoking rate and expired carbon
      monoxide (CO) levels would be greater among 15 female participants following a 24
      hour fasting period than when participants were not food-deprived. Food-deprived
      participants were also expected to endorse greater negative mood, smoking urges,
      and pleasure from smoking, as well as less positive mood. Analyses indicated that
      CO levels were significantly greater in the food-deprived condition than in the
      non-deprived condition (p=.05), although no differences were found in the number
      of cigarettes smoked during the laboratory session. Participants reported
      significantly lower Vigor-Activity in the food-deprived condition (p=.02). No
      differences were found between conditions in urges to smoke or pleasure from
      smoking. Findings suggest that nicotine intake may increase among females during
      acute food deprivation.

PMID- 18620817
TI  - Severity of heroin dependence in Taiwan: reliability and validity of the Chinese
      version of the Severity of Dependence Scale (SDS[Ch]).
AB  - The development of instruments to assess substance use that are easy to use,
      valid and reliable across cultures is an important task. The present study
      investigates the reliability and validity of the Chinese language version of the
      SDS (SDS([Ch])) when used to measure severity of dependence among heroin users in
      Taiwan (n=522). Data were collected on demographic data, heroin use behaviours,
      and criminal convictions. Taiwanese heroin users recorded high SDS([Ch]) scores
      and the results support the validity and reliability of the Chinese version of
      the SDS. A positive correlation was found between SDS([Ch]) scores and DSM-IV
      criteria for heroin dependence. SDS([Ch]) scores were positively related to
      heroin injection, frequency of heroin injection, spending on heroin, earlier age
      of onset of heroin use and more drug-related criminal convictions. The findings
      support the suggestion that the concept of dependence as assessed by the SDS has
      cross-cultural validity.

PMID- 18620818
TI  - Treatment-naive active alcoholics have greater psychiatric comorbidity than
      normal controls but less than treated abstinent alcoholics.
AB  - BACKGROUND: Most alcoholism research in the U.S. uses convenience samples of
      treated alcoholics. The findings from treated samples have traditionally been
      applied to all alcoholics, including the 75% of alcoholics who are untreated.
      Improper generalization from select samples to an entire population is called
      'Berkson's fallacy'. We compared untreated versus treated alcoholics, in order to
      ascertain whether both groups belonged to the same population with regard to
      psychiatric comorbidity. METHODS: We compared psychiatric comorbidity in 1)
      active treatment-naive alcoholics (TNA; n=86) 2) treated long-term abstinent
      alcoholics (TAA; n=52) and 3) non-alcoholic controls (NAC;n=118). We examined
      lifetime and current diagnoses, lifetime symptom counts, and psychological
      measures in the anxiety, mood and externalizing disorder domains. RESULTS: TNA
      did not differ from NAC in psychiatric diagnosis rates, were abnormal compared to
      NAC on all psychological measures, had more externalizing symptoms than NAC, and
      showed a strong trend for men to have more symptoms in the mood and anxiety
      domains. TAA compared to TNA had higher diagnosis rates (all domains), symptom
      counts (all domains), and psychological measures of deviance proneness, but were
      comparable to TNA on anxiety and mood psychological measures. CONCLUSIONS: The
      abnormal thinking (psychological measures) in TNA (versus NAC) does not extend to
      behavior (symptoms) to the degree that it does in TAA. These results underline
      the importance of the use of subdiagnostic measures of psychiatric comorbidity in
      studies of alcoholics. The finding of lesser comorbidity in TNA versus TAA
      confirms the presence of Berkson's fallacy in generalizing from treated samples
      to all alcoholics.

PMID- 18620819
TI  - Usage of antimicrobials and occurrence of antimicrobial resistance among bacteria
      from mink.
AB  - The usage of antimicrobials for treatment of mink and the occurrence of
      antimicrobial resistance among the most important bacterial pathogens in mink was
      investigated. The aim of the study was to provide data, which may serve as a
      basis for the formulation of recommendations for prudent use of antimicrobials
      for mink. A total of 164 haemolytic staphylococci, 49 haemolytic streptococci, 39
      Pseudomonas aeruginosa, 13 Pasteurella multocida, and 1093 Escherichia coli
      isolates from Danish mink were included in the study. A high frequency of
      resistance among S. intermedius was found for tetracyclines (54.7%), followed by
      penicillin (21.7%), lincosamides (20.4%), macrolides (19.1%), and spectinomycin
      (18.5%). Very low frequencies of resistance were recorded for other
      antimicrobials. The highest frequency among the E. coli isolates was recorded for
      ampicillin, streptomycin, sulphonamides, and tetracyclines, whereas resistance to
      other antimicrobials was rare. All P. aeruginosa were sensitive to gentamicin and
      colistin and sensitive or intermediate to enrofloxacin, whereas most isolates
      were resistant to all other antimicrobials. All P. multocida and haemolytic
      streptococci were sensitive to penicillin. There was a steady increase in the use
      of antimicrobials during the period 2001-2006, the majority of the prescribed
      amount being extended spectrum penicillins followed by aminoglycosides,
      sulphonamides with trimethoprim, and macrolides.

PMID- 18620821
TI  - Molecular characterization and SNPs analysis of the porcine Deleted in
      AZoospermia Like (pDAZL) gene.
AB  - The Deleted in AZoospermia Like (DAZL) gene is expressed in prenatal and
      postnatal germ cells. In this study, we cloned and characterized the porcine
      Deleted in AZoospermia Like (pDAZL) gene. We found the full-length coding
      sequence of the pDAZL encoded a protein of 295 amino acids with a RNA recognition
      motif (amino acids 41-111) and a DAZ repeat (amino acids 167-120). The deduced
      protein sequence of pDAZL is 92.5% and 91.5% similar to those of human and
      bovine, respectively. PCR-MspI-RFLP and PCR-TaqI-RFLP were established to detect
      an A/G mutation in intron 7 and a C/A mutation in intron 9, respectively.
      Associations of two SNPs with litter size traits were assessed in Large White
      (n=275) and DIV (n=128) pig populations, and the statistical analysis
      demonstrated that CC produced 0.716 more (P<0.05) piglets born alive than CD
      genotypes in Large White pigs at TaqI locus (C/A mutation in intron 9), and the
      dominance effect was 0.304 pig per litter (P<0.05). This result suggests that the
      pDAZL gene might be a good candidate gene of litter size trait and provides some
      marker information for marker-assisted selection (MAS).

PMID- 18620822
TI  - Studies on effect of Booroola (FecB) genotype on lifetime ewes' productivity
      efficiency, litter size and number of weaned lambs in Garole x Malpura sheep.
AB  - The FecB gene of Garole was introgressed into non-prolific Malpura sheep. The
      present study was conducted to evaluate the effects of FecB genotypes on
      cumulative lifetime (three lamb crops) litter size (CLS), cumulative number of
      weaned lambs (CWL) and cumulative ewe's productivity efficiency (CEPE) in 51
      Garole x Malpura (GM) crossbred sheep. The GM ewes of F(1) were selected and
      screened for FecB mutation using forced RFLP-PCR technique. The majority (78.4%)
      of F(1) GM individuals were carriers (FecB(B+)) for the FecB mutation. In first
      parity 55% FecB(B+) ewes gave births to multiple lambs. The FecB genotypes were
      significantly (P<0.01) associated with the CLS and CWL. The FecB(B+) ewes
      resulted in 65.6 and 62.1% higher CLS and CWL, respectively compared to non
      carriers. The CEPE was also affected significantly by the FecB genotypes at
      birth, weaning, 6 and 12 months of age. The FecB(B+) ewes weaned 20.9% higher
      total litter weight as compared to FecB++ ewes and at 12 months age the
      difference was 43.5% in favor of B+ ewes. The study indicated that the CLS, CWL
      and CEPE of carrier ewes (FecB(B+)) were comparatively higher than that of non
      carriers (FecB++).

PMID- 18620823
TI  - Effect of including growth factors and antioxidants in maturation medium used for
      in vitro culture of buffalo oocytes recovered in vivo.
AB  - This study examined the effect of including one of two growth factors (100 ng/ml
      IGF-1 or 20 ng/ml EGF) in combination with one of two antioxidants (50 microM
      cysteamine or 50 microM beta-mercaptoethanol) in maturation, fertilization and
      subsequent development of buffalo oocytes. The oocytes were recovered by in vivo
      ovum pick-up technique from six Murrah buffalo heifers twice a week over a period
      of 16 weeks. Immediately after ovum pick-up oocytes recovered from six donors
      were allocated randomly to five different maturation treatments. The control
      treatment was the basic maturation medium (MM; TCM-199 supplemented with 10% FBS,
      10 IU/ml LH, 0.5 microg/ml FSH, 1 microg/ml estradiol-17beta and 50 microg/ml
      gentamicin). The other four treatments consisted of the control maturation medium
      (MM) plus one combination of a growth factor and an antioxidant viz. IGF
      1+cysteamine; IGF-1+beta-ME; EGF+cysteamine or EGF+beta-ME. The total number of
      oocytes assigned to each maturation treatment ranged from 31 to 66. After
      maturation in different maturation medium, media used for in vitro fertilization
      and subsequent development of embryo was same for all groups. Data were analysed
      using Chi-square test. The maturation rate observed for the growth factor plus
      antioxidant treatments was similar to that for the control (90.4%). The highest
      cleavage rate recorded in the IGF-1+cysteamine treatment (71.9%) which was
      significantly higher (P<0.05) than the IGF-1+beta-ME (45.2%) and EGF+beta-ME
      (46.4%) treatments, but not significantly differ from the control (63.8%) and
      EGF+cysteamine treatment (60.7%). The proportion of cleaved oocytes those
      developed to blastocyst stage was significantly higher in the IGF-1+cysteamine
      treatment (52.2%; P<0.05) than in the control (23.3%), the EGF+cysteamine (13.5%)
      or the EGF+beta-ME (7.7%) treatments, but did not differ significantly from the
      IGF-1+beta-ME (28.6%) treatment. Following non-surgical transfer of 15 embryos to
      14 synchronized recipients, four became pregnant and only one recipient sustained
      the pregnancy as long as 4.5 months when spontaneous abortion occurred. It was
      concluded that supplementing the maturation medium with IGF-1+cysteamine improved
      the production of buffalo embryos significantly in vitro culture.

PMID- 18620824
TI  - Nails of newborns in monitoring drug exposure during pregnancy.
AB  - This project was developed to investigate the usefulness of newborn nails for
      monitoring in utero drug exposure. Cocaine, benzoylecgonine, morphine, methadone,
      caffeine, nicotine, and cotinine were determined in nail samples from the first 3
      months of life of 25 newborns abandoned immediately after birth (group 1) and of
      33 babies born at the local maternity hospital whose families were recruited on a
      voluntary basis (group 2). All substances were measured by gas chromatography
      mass spectrometry (detection limit: 0.025 ng/mg). Moreover, analytical results
      were compared with mothers' self-reported habits when the information was
      available. In group 1, 12 nails were found positive for caffeine and 13 for both
      nicotine and cotinine. Six samples tested cocaine- (range, median: 0.14-0.25,
      0.175 ng/mg) and benzoylecgonine-positive (range, median: 0.12-0.20, 0.165
      ng/mg). Both nicotine and cocaine were always retrieved together with their main
      metabolite. Morphine was found in four samples (range, median: 0.10-0.15, 0.125
      ng/mg), methadone in five samples (range, median: 0.12-0.26, 0.170 ng/mg) that
      were found negative for all other compounds. In group 2, two samples tested
      positive for methadone (0.16, 0.17 ng/mg). The mothers self-report of the use of
      coffee always corresponded to caffeine positivity in the newborn nails (n=6),
      whereas six samples tested positive for nicotine and/or cotinine with a non
      smoking mother. Sixteen out of the 33 samples of group 2 tested negative for all
      compounds. In conclusion, for the first time, results showed that, once that
      sample collection problems are solved, nails of the first period of life can be a
      very interesting indicator of in utero drug exposure.

PMID- 18620825
TI  - Temporal expression of immediate early gene mRNA during the supravital reaction
      in mouse brain and lung after mechanical asphyxiation.
AB  - In forensic pathology, the reactions that occur in the body from somatic death to
      cell death are commonly termed "supravital reactions". There are many reports of
      grossly visible and microscopic supravital reactions; however, few papers are
      available on the supravital reaction concerning gene expression. The aim of this
      study was to examine the gene expression of immediate early genes (IEGs)
      including c-fos, fos-B and c-jun in mechanically asphyxiated mouse brain and lung
      after somatic death and to identify the IEGs expressed at the point of supravital
      reaction in the brain and lung. Our results confirm that the expression of IEGs
      changed after death during supravital reaction and that the alterations differed
      according to the cause of death and the types of organ examined. In addition, IEG
      expression significantly increased following mechanical asphyxia. These results
      suggest that there is a specific pattern of gene expression following asphyxia.
      It is therefore important to identify the specific genes involved, as this may
      give significant information to aid in the post-mortem diagnosis of strangulation
      and hanging.

PMID- 18620826
TI  - Comparison of auditory steady-state responses and auditory brainstem responses in
      audiometric assessment of adults with sensorineural hearing loss.
AB  - OBJECTIVE: Many of the medico-legal patients who claimed compensation may
      exaggerate hearing loss that varies in degree, nature, and laterality. The
      purpose of this study was to investigate whether Auditory Steady-State Response
      (ASSR) could be used to predict the hearing level of adults, and whether ASSR
      could become a better testing method than Auditory brainstem response (ABR) in
      audiometric assessment of adults with sensorineural hearing loss. METHODS: This
      was a prospective study, which was conducted in a tertiary referral hospital.
      From January to June 2007, 142 subjects (284 ears) with varying degrees of
      sensori-neural hearing impairment were included in this study. Four commonly used
      frequencies (500, 1000, 2000, 4000Hz) were evaluated. All subjects received pure
      tone audiometry, multi-channel ASSR, and ABR tests for threshold measurement. The
      correlation of pure tone thresholds with ASSR and ABR thresholds were assessed.
      RESULTS: Between multi-channel ASSR and pure tone thresholds, a difference of
      less than 15dB was found in 71% while a difference of less than 25dB was found in
      89% of patients. The correlation coefficient (r) of multi-channel ASSR and pure
      tone thresholds were 0.89, 0.95, 0.96, and 0.97 at 500, 1000, 2000, and 4000Hz,
      respectively. The strength of the relationship increased with increasing
      frequency. On the other hand, between ABR and pure-tone thresholds, a difference
      of less than 15dB was found in 31%; a difference of less than 25dB was found in
      62% of patients. The r correlation value for ABR and pure tone thresholds was
      0.83. CONCLUSION: ASSR is a more reliable test for the accurate prediction of
      auditory thresholds than ABR. It can be a powerful and convenient electro
      physiologic examination tool for clinically assessing of adults with
      sensorineural hearing loss.

PMID- 18620827
TI  - Laterofixation of the vocal fold using an endo-extralaryngeal needle carrier for
      bilateral vocal fold paralysis.
AB  - OBJECTIVES: Laterofixation of the vocal fold is a simple and reliable surgical
      intervention for laryngeal obstruction due to bilateral vocal fold fixation to
      obtain sufficient glottal space. Nevertheless, it has some technical
      disadvantages. This report summarizes the surgical outcomes in patients who
      underwent laterofixation of the vocal fold with or without the use of an endo
      extralaryngeal needle carrier (EENC). METHODS: A prospective study of 11
      consecutive patients with bilateral vocal fold paralysis. All of the patients
      underwent unilateral vocal fold laterofixation. Six patients were assigned to the
      non-EENC group and five to the EENC group. The surgical outcomes were evaluated,
      including the operating time and respiratory and phonatory functions. RESULTS:
      The operating time was 44% shorter in the EENC group and less skin incisions were
      required. Postoperatively, the dyspnea was eliminated in all of the patients in
      both groups, and the six patients who required a tracheotomy were successfully
      decannulated. Spirometry confirmed the improvements in %FEV(1) and %PEF in the
      two groups. Postoperative voice function was socially acceptable in all patients,
      and it tended to be better in the non-EENC group. In the EENC group, one patient
      developed a minor submucosal hematoma and another patient had a recurrence of
      dyspnea 2 months postoperatively, probably due to thread disruption. CONCLUSION:
      The present study confirms that laterofixation of the vocal fold with or without
      EENC relieves laryngeal obstruction. Surgery with the EENC is simpler and quicker
      than the conventional procedure. However, the surgery with the EENC has some
      disadvantages, including likely problems with the thread and downward traction on
      the vocal fold. Surgeons should be aware of these possible shortcomings.

PMID- 18620828
TI  - Considerations on the physiopathological mechanism of inner ear damage induced by
      intravenous cocaine abuse: cues from a case report.
AB  - OBJECTIVE: Aim of the following paper is to discuss about the possible
      etiopathogenetic mechanisms of inner ear damage induced by cocaine abuse.
      Unfortunately the data concerning this topic are very limited; the authors are
      then presenting a literature review, also discussing the clinical presentation
      and the possible therapeutical approach of a clinical case of bilateral sudden
      sensorineural hearing loss following i.v. injection of cocaine. PATIENTS: Case
      report. INTERVENTION: A strictly audiological evaluation has been performed, in
      order to identify the cochlear lesion site(s) and to provide the best medical
      treatment. CONCLUSIONS: To our knowledge, this is the first report of acute
      cocaine intoxication with sudden bilateral hearing loss. Further studies are
      required in order to understand the effects of these substances on the inner ear
      cells and metabolism.

PMID- 18620829
TI  - Refraction-based 2D, 2.5D and 3D medical imaging: stepping forward to a clinical
      trial.
AB  - An attempt at refraction-based 2D, 2.5D and 3D X-ray imaging of articular
      cartilage and breast carcinoma is reported. We are developing very high contrast
      X-ray 2D imaging with XDFI (X-ray dark-field imaging), X-ray CT whose data are
      acquired by DEI (diffraction-enhanced imaging) and tomosynthesis due to
      refraction contrast. 2D and 2.5D images were taken with nuclear plates or with X
      ray films. Microcalcification of breast cancer and articular cartilage are
      clearly visible. 3D data were taken with an X-ray sensitive CCD camera. The 3D
      image was successfully reconstructed by the use of an algorithm newly made by our
      group. This shows a distinctive internal structure of a ductus lactiferi (milk
      duct) that contains inner wall, intraductal carcinoma and multifocal
      calcification in the necrotic core of the continuous DCIS (ductal carcinoma in
      situ). Furthermore consideration of clinical applications of these contrasts made
      us to try tomosynthesis. This attempt was satisfactory from the view point of
      articular cartilage image quality and the skin radiation dose.

PMID- 18620830
TI  - Cardiac CT angiography after coronary artery surgery in children using 64-slice
      CT scan.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of 64
      slice CT with that of invasive angiography in the detection of graft and/or
      coronary angioplasty stenosis in children who had undergone coronary artery
      surgery. POPULATION AND METHODS: Fifteen consecutive children (8 male and 7
      female; age 9.2+/-6.1 years) underwent 64-slice CT because of chest pain or ECG
      changes mean 4.8+/-3.7 years after surgical coronary artery surgery; 10 patients
      had coronary angioplasty using a patch from the saphenous vein, four had mammary
      artery bypass, and one had saphenous vein bypass. Six main segments of the
      coronary arteries and all the bypass graft considered as a single segment were
      analyzed and compared with invasive angiography used as the reference standard.
      RESULTS: CT correctly identified the four children with coronary angioplasty and
      mammary graft lesions that were confirmed by conventional angiography: one
      patient had a significant stenosis (>50% stenosis) at the mammary bypass graft
      anastomosis site; three other had non-significant stenosis (<50% stenosis)
      including a mild lesion of the saphenous vein patch in two patients and a mild
      lesion at the anastomosis site of the mammary bypass in one. All segments
      identified as normal by CT in the other 11 children were also found to be normal
      by conventional angiography. CONCLUSION: In centers expert in this technique, 64
      slice CT scanning is a promising, rapid, and useful diagnostic technique for
      evaluating both coronary angioplasty and bypass graft lesions in children who had
      undergone coronary artery surgery.

PMID- 18620831
TI  - Radiocontrast media-associated exanthema: identification of cross-reactivity and
      tolerability by allergologic testing.
AB  - BACKGROUND: All iodinated radiocontrast media (RCM) may cause hypersensitivity
      reactions, either immediate-type within 5-10 min of RCM injection or delayed
      type, which become apparent more than 1h after RCM exposure. Delayed-type
      hypersensitivity to RCM may pose a problem for future radiologic investigations
      because due to possible immunological cross-reactivity all iodinated RCM are
      usually avoided. OBJECTIVE: The aim of this study was not only to identify the
      causal RCM for the exanthema but also to demonstrate that patients may receive
      alternative iodinated RCM despite a history of RCM-induced allergic exanthema.
      METHODS: We evaluated 32 patients with a history of exanthema after RCM
      application using standardized patch, prick and intradermal skin testing. In case
      of positive skin tests intravenous challenges with skin-test-negative RCM were
      performed to identify non-ionic monomer RCM which are tolerated. RESULTS: In 6
      out of 32 patients skin tests strongly suggested a delayed-type non-IgE-mediated
      allergic hypersensitivity to the RCM iomeprol (3x), iopromide (2x), and
      iopamidol. In 4 patients alternative non-ionic monomer RCM (2x iosarcol,
      iopromide, and iomeprol) were identified by controlled challenge tests.
      CONCLUSIONS: The evaluation of patients with RCM-associated exanthema should
      always include appropriate skin tests ensuring that patients with a delayed-type
      allergic RCM-induced exanthema are not missed. Moreover, allergologic testing may
      identify alternative RCM of the group of non-ionic monomers, which are tolerated
      in future radiologic investigations.

PMID- 18620832
TI  - The direct comparison of health and ulcerated stomach tissue: a multiple probe
      microdialysis sampling approach.
AB  - The ability to directly compare gastric ulcerated and healthy tissue would aid in
      the understanding of the physiological differences between these tissue types.
      Presently, these comparisons can only be drawn by the use of separate animal
      groups, which results in increased study variability. The focus of this research
      was to develop a four-probe microdialysis sampling approach to directly compare
      ulcerated and healthy tissue in the same animal. After controlled chemical ulcer
      induction, probes were implanted in the ulcerated and healthy stomach submucosa,
      stomach lumen and in the blood. To assess the significance of this multiple probe
      approach, drug concentrations in each probe location were monitored after
      selected compounds were dosed to the ligated stomach by oral gavage. Analysis of
      the dialysate samples was performed by HPLC-UV and concentration-time curves and
      pharmacokinetics analyses were used to determine differences between these tissue
      types.

PMID- 18620833
TI  - Zabofloxacin (DW-224a) activity against Neisseria gonorrhoeae including quinolone
      resistant strains.
AB  - Zabofloxacin, a new fluoroquinolone compound (DW-224a), was tested by reference
      agar dilution methods against 35 strains of multiresistant Neisseria gonorrhoeae.
      The potency of zabofloxacin (MIC(50), 0.016 microg/mL) was generally comparable
      with azithromycin but 8-fold superior to ciprofloxacin. This novel naphthyridine
      should be explored as an alternative therapy for quinolone-nonsusceptible
      gonorrhea and Chlamydia trachomatis infections.

PMID- 18620834
TI  - Diagnostic utility of interferon-gamma-induced protein of 10 kDa (IP-10) in
      tuberculous pleurisy.
AB  - Tuberculous pleuritis (TP) is characterized by predominant Th1 immune response.
      We observed significantly high levels of interferon gamma (IFN-gamma) and
      chemokines such as IP-10, monokine induced by IFN-gamma (MIG), interleukin 8 (IL
      8), monocyte chemotactic protein (MCP)-1, and macrophage inflammatory protein
      (MIP)-1alpha in tuberculous pleural effusions. In the current study, we evaluated
      the diagnostic utility of IFN-gamma-dependent chemokine especially IP-10. The
      receiver operating characteristics (ROC) curve analyses based on cytometric bead
      array values depicted high sensitivity only for IP-10 (76.3%) followed by IFN
      gamma (73.7%). The ELISA test further confirmed the significantly high levels of
      IFN-gamma and IP-10 in TP. The ROC curve analysis again demonstrated high area
      under the curve (AUC) for IP-10 (0.966) than the referred diagnostic marker IFN
      gamma (0.930). The better sensitivity (84.2% for IFN-gamma and 89.2% for IP-10)
      and equal specificity (95.7%) of IP-10 assay compared with IFN-gamma suggest that
      IP-10 is a potential diagnostic marker for evaluating TP.

PMID- 18620836
TI  - Physiologic coarctation of the aorta resulting from proximal protrusion of
      thoracic aortic stent grafts into the arch.
AB  - Graft collapse is a known complication of thoracic aortic stent grafting,
      particularly in cases of traumatic thoracic aortic transection, when a typically
      smaller diameter aorta is repaired with a relatively large diameter device. In
      contrast, obstruction of the aorta from a stent graft that protrudes into the
      aortic arch but does not collapse is a less common complication of thoracic
      aortic stent grafting that can present as a functional aortic coarctation. We
      describe here two cases of physiologic coarctation of the aorta caused by stent
      graft protrusion into the arch that were successfully treated with stent graft
      explantation and open aortic reconstruction.

PMID- 18620835
TI  - When pregnant patients disclose substance use: missed opportunities for
      behavioral change counseling.
AB  - OBJECTIVE: The first obstetric visit is an opportunity to provide counseling to
      women with substance abuse risks, including smoking, drug use, and alcohol use.
      Little is known about how obstetric care providers and patients discuss these
      issues. Our objective was to examine patient-provider communication about
      substance use behaviors during these visits. METHODS: We audio-taped and
      transcribed verbatim first prenatal visits in an outpatient hospital clinic, then
      qualitatively analyzed them for content and process of communication using
      modified grounded theory methods. RESULTS: Twenty-nine providers (21 residents, 5
      midwives, 3 nurse practitioners) and 51 patients participated. Twenty-five
      patients were smokers, 4 used alcohol, and 11 used drugs. Provider responses to
      smoking disclosures included discussions of risks, encouragement to quit-cut
      down, affirmation of attempts to quit-cut down, and referral to smoking cessation
      programs. Responses to alcohol or drug disclosures included only a general
      statement regarding risks and referral to genetics. CONCLUSION: Providers were
      less attentive to alcohol and drugs than smoking where they had pre-established
      patterns of response. PRACTICE IMPLICATIONS: Providers should discuss behavioral
      change strategies and motivations with pregnant patients who use drugs and/or
      alcohol as well as those who smoke.

PMID- 18620837
TI  - The effect of smoke-free homes on smoking behavior in the U.S.
AB  - BACKGROUND: Evidence from longitudinal population surveys is needed to establish
      whether smoke-free homes might influence smoking behavior. METHODS: The Tobacco
      Use Supplement of the nationally representative U.S. Current Population Survey
      (TUS-CPS) interviewed 3292 adult recent smokers in 2002 and again 12 months
      later. Both surveys measured smoking status, rules on smoking in the home, and
      the number of cigarettes smoked per day (cpd). For the main study outcome, an
      early marker of successful cessation (>or=90 days quit) was used. Analysis was
      completed in 2008. RESULTS: In the 12 months ending February 2003, the prevalence
      of smoke-free homes among recent smokers increased from 33% to 39%. A smoke-free
      home at baseline was associated with >or=90 days cessation at follow-up (10.9% vs
      6.2%, AOR=1.44; 95% CI=0.97, 2.21), and those who maintained a smoke-free home
      were more likely to be >or=90 days quit than those who did not (12.9% vs 5.7%,
      AOR=1.99; 95% CI=0.93, 4.25). However, adopting a smoke-free home during the year
      was associated with a nearly fivefold increase in the percentage of >or=90 days
      quit (AOR=4.81; 95% CI=3.06, 7.59). This increase was seen among all smokers,
      including moderate-to-heavy smokers (>or=90 days quit: a smoke-free home=13.0% vs
      no smoke-free home=2.9%, p<0.001). Among continuing smokers with a smoke-free
      home at baseline, maintenance of te smoke-free home was associated with a decline
      in consumption (micro=or-2.18; 95 CI=or-1.24; -3.10 cpd). Among continuing
      smokers with no smoke-free home at baseline, adoption of that status was also
      associated with a decline in consumption (micro=or-1.72; 95% CI=or-0.58; -2.85
      cpd). CONCLUSIONS: This study provides strong evidence that the adoption of a
      smoke-free home is associated with successful quitting among smokers in the U.S.

PMID- 18620838
TI  - Driver and passenger seatbelt use among U.S. high school students.
AB  - BACKGROUND: In 2005, 40% of motor-vehicle occupant deaths in the group aged 16-19
      years involved passengers. Although seatbelts can reduce crash mortality by 50%
      or more, little is known about the differences in driver-versus-passenger
      seatbelt use among teens. METHODS: In 2007, data from the 2001 and 2003 Youth
      Risk Behavior Surveys were analyzed for 12,731 black, white, and Hispanic high
      school students aged >or=16 years reporting seatbelt use as both drivers and
      passengers. Seatbelt use was compared for driver- and passenger-seat positions,
      and stratified by age, gender, race/ethnicity, school grades, and histories of
      either drinking and driving or riding with a drinking driver. RESULTS: Overall,
      59% of students always used seatbelts when driving, but only 42% always buckled
      up as passengers. Across all covariate strata, passenger seatbelt use was
      significantly less prevalent than driver seatbelt use (p<0.001). A concordance
      analysis showed that only 38% of students always wore seatbelts both when driving
      and while riding as a passenger. Multivariate analyses indicated that, regardless
      of seat position, seatbelt use was lower for young men, blacks, students with
      poor grades, and students who reported either drinking and driving or riding with
      a drinking driver. CONCLUSIONS: U.S. high school students aged >or=16 years are
      significantly less likely to wear seatbelts as passengers than as drivers.
      Interventions designed to promote seatbelt use among teens need to address this
      disparity.

PMID- 18620840
TI  - Multivariable adjustments counteract spectrum and test review bias in accuracy
      studies.
AB  - OBJECTIVES: The STAndards for Reporting studies of Diagnostic accuracy (STARD)
      for investigators and editors and the Quality Assessment of Diagnostic Accuracy
      Studies (QUADAS) for reviewers and readers offer guidelines for the quality and
      reporting of test accuracy studies. These guidelines address and propose some
      solutions to two major threats to validity: spectrum bias and test review bias.
      STUDY DESIGN AND SETTING: Using a clinical example, we demonstrate that these
      solutions fail and propose an alternative solution that concomitantly addresses
      both sources of bias. We also derive formulas that prove the generality of our
      arguments. RESULTS: A logical extension of our ideas is to extend STARD item 23
      by adding a requirement for multivariable statistical adjustment using
      information collected in QUADAS items 1, 2, and 12 and STARD items 3-5, 11, 15,
      and 18. CONCLUSION: We recommend reporting not only variation of diagnostic
      accuracy across subgroups (STARD item 23) but also the effects of the
      multivariable adjustments on test performance. We also suggest that the QUADAS be
      supplemented by an item addressing the appropriateness of statistical methods, in
      particular whether multivariable adjustments have been included in the analysis.

PMID- 18620839
TI  - Assessing mitral valve area and orifice geometry in calcific mitral stenosis: a
      new solution by real-time three-dimensional echocardiography.
AB  - BACKGROUND: Planimetry of mitral valve area (MVA) is difficult in calcific mitral
      stenosis (CaMS) in which limiting orifice is near the annulus, and unlike
      rheumatic mitral stenosis (RhMS), does not present an area for planimetry at the
      leaflet tips. Moreover, pressure half time (PHT)-derived MVA (MVA(PHT)) has
      limitations in patients with CaMS in whom there are coexisting conditions that
      affect LV chamber compliance. We tested the hypothesis that real-time 3
      dimensional echocardiography (RT3D) can guide measurement at the narrowest
      orifice in CaMS. METHODS: In 34 patients with CaMS, MVA by RT3D (MVA(RT3D)) was
      obtained using a color-defined planimetry technique performed "en face" at the
      smallest annular orifice cross-section (diastolic maximum). MVA(RT3D) and
      MVA(PHT) were compared with an independent standard: MVA by continuity equation
      (MVA(CEQ)). In a subgroup of 10 patients with CaMS or RhMS, the 3-dimensional
      shape of the stenotic mitral valve was examined, guided by color flow mapping.
      RESULTS: MVA(PHT) overestimated the mitral orifice area compared with MVA(CEQ)
      (2.01 +/- 0.52 cm(2) vs 1.75 +/- 0.46 cm(2); P = .037), whereas there was no
      significant difference in MVA(RT3D) and MVA(CEQ) (1.83 +/- 0.52 cm(2) vs 1.75 +/-
      0.46 cm(2), respectively, P = .61). MVA(RT3D) had a greater correlation with MVA
      (CEQ) than MVA(PHT) (R = 0.86 vs 0.59 MVA(RT3D) vs MVA(PHT), respectively). There
      was better agreement between MVA by RT3D and MVA by continuity equation than MVA
      by PHT and MVA by continuity equation (difference in MVA: 0.23 +/- 0.15 cm(2) vs
      0.43 +/- 0.29 cm(2); P < .0001, MVA(RT3D) - MVA(CEQ) vs MVA(PHT) - MVA(CEQ,)
      respectively). In CaMS, there was a tubular geometry to the valve shape. In
      contrast, RhMS had a doming funnel-shaped geometry. CONCLUSION: RT3D provides an
      accurate measurement of MVA in CaMS. In contrast with the doming valve shape
      present in RhMS, the limiting anatomic orifice area occurs at the annulus in CaMS
      as measured by RT3D and reflects the effective orifice area as present in a
      tubular valve geometry.

PMID- 18620841
TI  - Publication bias was not a good reason to discourage trials with low power.
AB  - OBJECTIVE: The objective was to investigate whether it is justified to discourage
      trials with less than 80% power. Trials with low power are unlikely to produce
      conclusive results, but their findings can be used by pooling then in a meta
      analysis. However, such an analysis may be biased, because trials with low power
      are likely to have a nonsignificant result and are less likely to be published
      than trials with a statistically significant outcome. STUDY DESIGN AND SETTING:
      We simulated several series of studies with varying degrees of publication bias
      and then calculated the "real" one-sided type I error and the bias of meta
      analyses with a "nominal" error rate (significance level) of 2.5%. RESULTS: In
      single trials, in which heterogeneity was set at zero, low, and high, the error
      rates were 2.3%, 4.7%, and 16.5%, respectively. In multiple trials with 80%-90%
      power and a publication rate of 90% when the results were nonsignificant, the
      error rates could be as high as 5.1%. When the power was 50% and the publication
      rate of non-significant results was 60%, the error rates did not exceed 5.3%,
      whereas the bias was at most 15% of the difference used in the power calculation.
      CONCLUSION: The impact of publication bias does not warrant the exclusion of
      trials with 50% power.

PMID- 18620842
TI  - Markov random field-based clustering applied to the segmentation of masses in
      digital mammograms.
AB  - In this paper we propose a new pixel clustering model applied to the analysis of
      digital mammograms. The clustering represents here the first step in a more
      general method and aims at the creation of a concise data-set (clusters) for
      automatic detection and classification of masses, which are typically among the
      first symptoms analysed in early diagnosis of breast cancer. For the purpose of
      this work, a set of mammographic images has been employed, that are 12-bit gray
      level digital scans and as such, are inherently inhomogeneous and affected by the
      noise resulting from the film scanning. The image pixels are described only by
      their intensity (gray level), therefore, the available information is limited to
      one dimension. We propose a Markov random field (MRF)-based technique that is
      suitable for performing clustering in an environment which is described by poor
      or limited data. The proposed method is a statistical classification model, that
      labels the image pixels based on the description of their statistical and
      contextual information. Apart from evaluating the pixel statistics, that
      originate from the definition of the K-means clustering scheme, the model expands
      the analysis by the description of the spatial dependence between pixels and
      their labels (context), hence leading to the reduction of the inhomogeneity of
      the output. Moreover, we define a probabilistic description of the model, that is
      characterised by a remarkable simplicity, such that its realisation can be easily
      and efficiently implemented in any high- or low-level programming language, thus
      allowing it to be run on virtually any kind of platform. Finally, we evaluate the
      algorithm against the classical K-means clustering routine. We point out
      similarities between the two methods and, moreover, show the advantages and
      superiority of the MRF scheme.

PMID- 18620843
TI  - Prospective study of digital radiographs versus conventional screen films in
      Small Bowel Follow-Through examination.
AB  - PURPOSE: To prospectively compare subjective radiological quality, radiation dose
      and effect on workflow using digital radiography (DR) vs. conventional screen
      film (SF) radiography in the Small Bowel Follow-Through (SBFT) examination.
      METHODS: Five attending and four resident radiologists compared hard-copy images
      from 11 SBFT examinations, for which every patient had a defined pair of SF and
      DR images taken 20-30 min apart. SF and DR were performed with equivalent
      exposure data. Overall image quality, intestinal mucosa definition and bone
      visualization were graded on a 5-point scale, with 5 being the highest value.
      Thus, 11 patients had three criteria judged by nine observers in two modalities
      for a total of 594 observations of image quality. The radiation doses and effect
      on workflow were also compared. Statistical analysis was performed with the Mann
      Whitney U test. RESULTS: The mean scores on DR and SF for overall image quality,
      intestinal mucosa definition and bone visualization were 4.49 vs. 3.17, 4.38 vs.
      3.4, and 4.5 vs. 2.4, respectively (p<0.001 in all cases). The average radiation
      dose with DR was 0.93+/-0.54 cGy, and -1.58+/-0.63 cGy with SF (p=0.016),
      reflecting a 41% dose reduction. Production of a DR image by technicians took
      3.5+/-1.3 min vs. 5.5+/-1.5 min for SF (p=0.002). CONCLUSION: Subjective image
      quality of hard-copy digital radiographs of the small bowel through examination
      is superior to images obtained with conventional radiographs, with an associated
      reduction of 41% in radiation dose and increased efficiency.

PMID- 18620844
TI  - Post operative hiccups.

PMID- 18620845
TI  - Growth inhibition of a tongue squamous cell carcinoma cell line (Tca8113) in
      vitro and in vivo via siRNA-mediated down-regulation of skp2.
AB  - Human S-phase kinase-associated protein (skp) 2, the specific ubiquitin ligase
      subunit that targets the negative regulator p27(Kip1) of the cell cycle and
      brings about its degradation, is overexpressed in various cancers, including
      human oral squamous cell carcinomas; its expression levels are inversely related
      to those of p27(Kip1) in these cells. Recently, a technique known as RNA
      interference (RNAi) has successfully been applied to mammalian cells. In order to
      evaluate the applications of the RNAi strategy for cancer gene therapy, the
      authors treated Tca8113 cells expressing high levels of Skp2 with a small
      interfering RNA (siRNA) expression plasmid vector targeting skp2 in vitro and in
      vivo. They demonstrated that the Skp2 protein levels decreased, while the
      p27(Kip1) protein levels increased in Tca8113 cells transfected with skp2siRNA.
      Further, skp2siRNA inhibited growth in the Tca8113 cells in vitro and suppressed
      tumor proliferation in vivo. These results suggest that siRNA-mediated silencing
      of the skp2 gene may represent a useful strategy for gene therapy of tumors
      expressing high levels of Skp2.

PMID- 18620846
TI  - Functional characterisation of altered outer membrane proteins for tetracycline
      resistance in Escherichia coli.
AB  - Alterations in the outer membrane (OM) proteome in response to tetracycline have
      been reported in Escherichia coli K-12, but information regarding their
      functional profile is not available. In this study, upregulation of FimD, Tsx,
      OmpW, OmpC and TolC and downregulation of LamB in response to tetracycline were
      detected and confirmed by two-dimensional gel electrophoresis subproteomics and
      Western blotting, respectively. The ability of the six altered OM proteins was
      investigated using genetically modified strains with gene deletion or
      complementation. Of the six mutants tested, DeltatolC and DeltaompC showed
      decreased minimum inhibitory concentrations (MICs) and DeltalamB showed an
      increased MIC. These changes in the three mutants could be completely recovered
      by gene complementation. The survival capability of gene-deleted was
      significantly increased in DeltalamB mutants and significantly decreased in
      DeltatolC, DeltaompC, DeltaompW and Deltatsx with respect to the control; a more
      significant decrease was observed in DeltatolC and DeltaompC than DeltaompW and
      Deltatsx. These changes were also observed in their complemented strains. Our
      results indicate that LamB, OmpC and TolC are important OM proteins for
      tetracycline resistance in E. coli. Meanwhile, our data suggest that functional
      validation is required to investigate whether the altered proteins obtained from
      two-dimensional gel electrophoresis play a direct or indirect role in phenotypic
      changes.

PMID- 18620847
TI  - Molecular characterisation of high-level ampicillin-resistant Enterococcus
      faecium isolates from hospitalised patients in Tunis.

PMID- 18620849
TI  - Abuse liability of intra-nasal midazolam in inhaled-cocaine abusers.
AB  - Intra-nasally instilled benzodiazepines have been proposed for acute anxiety
      episodes. However, routes with faster absorption may increase abuse liability.
      This study compared abuse liability of intra-nasal midazolam between subjects
      with a history of intra-nasal drug abuse and non-psychiatric subjects on a single
      blind randomized controlled trial. Thirty-one inhaled-cocaine abusers and 34
      normal volunteers received either 1 mg intra-nasal midazolam or active placebo.
      Visual analogue scales assessing desire to repeat the experience (ER) and
      Experience Liking (EL) assessed abuse liability. Profile analysis for repeated
      measures showed a significant effect of time over ER (F([5,57])=3.311, p=0.011)
      and EL (F([5,57])=3.947, p=0.004), diagnostic group (cocaine abusers scoring
      higher on both - F([5,57])=5.229, p=0.026; F([5,57])=4.946, p=0.030), regardless
      of the administered substance. It is concluded that the intra-nasal route does
      not seem to pose risks for non-psychiatric individuals, but it may represent a
      risk in itself for subjects with a history of drug abuse through this path.

PMID- 18620848
TI  - Genetic characterisation of CTX-M-15-producing Klebsiella pneumoniae and
      Escherichia coli strains isolated from stem cell transplant patients in Tunisia.
AB  - Characterisation of extended-spectrum beta-lactamase (ESBL) genes and their
      genetic environments as well as the presence of integrons were analysed in nine
      Klebsiella pneumoniae and two Escherichia coli ESBL-positive isolates recovered
      in the Centre of Bone Marrow Transplantation of Tunisia. All strains harboured
      the bla(CTX-M-15) gene and presented minimum inhibitory concentrations for
      cefotaxime and ceftazidime of 256-1024 mg L(-1) and 16-512 mg L(-1),
      respectively, and eight of them showed different pulsed-field gel electrophoresis
      patterns. The bla(OXA-1) and bla(TEM-1) genes were detected in eight and ten
      strains, respectively. In addition, bla(SHV-1), bla(SHV-11) and bla(SHV-27) were
      found in six, one and one K. pneumoniae strains, respectively. The new variant
      bla(SHV-103) was characterised in one K. pneumoniae strain. The intI1 gene was
      detected in eight K. pneumoniae strains and the dfrA5+ereA2 and aadA gene
      cassettes were found in one and five strains, respectively. All strains harboured
      a 70 kb plasmid, and its transference in addition to bla(CTX-M-15), bla(TEM-1b)
      and bla(OXA-1) genes was demonstrated from three K. pneumoniae to E. coli. ISEcp1
      and orf477 were located upstream and downstream, respectively, of the bla(CTX-M
      15) gene in 10 strains. The occurrence of the bla(CTX-M-15) gene in unrelated
      strains might have originated from the dissemination of mobile genetic elements
      in which ISEcp1 may have played an important role.

PMID- 18620850
TI  - Anions bonded on the supramolecular hydrogel surface as the growth center of
      biominerals.
AB  - In this work, a supramolecular hydrogel formed from N,N',N''-tris(3-pyridyl)
      trimesic amide was reported to serve as the matrix for the growth of biominerals.
      The organic hydrogel scaffold contains nitrogen heterocyclic ring and amide
      groups that can bind anions of the mineral (specially here, carbonate ions and
      phosphate ions) through hydrogen bonding interactions and act as the
      biomineralization active sites for growing biominerals. Calcium carbonate
      nucleated on the site of the hydrogel fiber where carbonate ions bonded and left
      obvious hydrogel fiber prints on the obtained product. Calcium phosphate grew
      into curved platelike nanostructures along the hydrogel fibrous network. XRD
      pattern and FT-IR spectra confirmed the formation of minerals on the hydrogel.
      The results indicate that the hydrogen bonding interaction can provide strong
      enough binding force for the growth of the minerals on organic scaffolds. Our
      finding extends the organic scaffolds into biodegradable small molecule hydrogels
      and also extends the growth centers of the minerals from conventional carboxylate
      groups binding Ca(2+) to amide and pyridyl groups binding PO(4)(3-).

PMID- 18620851
TI  - Enhanced blood compatibility of polyurethane functionalized with sulfobetaine.
AB  - The purpose of this work is to develop a biocompatible polyurethane surface by
      the tailoring of sulfobetaine. The polyurethane film was first grafted
      polymerization with acrylic acid by ozonization, followed by immobilizing
      sulfobetaine via two routes: (i) synthesize primary amine group terminated
      sulfobetaine and then couple onto the surface of polyurethane using 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide hydrochloride (EDC); (ii) couple the primary
      amine group terminated tertiary amine onto the surface of polyurethane primarily
      using EDC and then form sulfobetaine through a ring-opening reaction between
      tertiary amine and 1,3-propanesultone (PS). The reaction process was monitored
      with attenuated total reflection Fourier transform infrared spectroscopy (ATR
      FTIR) and X-ray photoelectron spectroscopy (XPS). The blood compatibility was
      evaluated by a hemolytic test and platelet-rich plasma (PRP) adhesion experiment.
      Little hemolysis took place on the surface of polyurethane grafted with
      sulfobetaine. Platelets adhering on the surface of grafted polyurethane decreased
      greatly as compared to the original after 1 and 3h of incubation with PRP.

PMID- 18620852
TI  - The economic burden of chronic obstructive pulmonary disease (COPD) in a U.S.
      Medicare population.
AB  - RATIONALE: Although the economic burden of COPD has gained attention in recent
      years, data on the costs of COPD among U.S. Medicare beneficiaries are lacking.
      METHODS: This study used administrative claims and eligibility records from a
      large U.S. multi-state Medicare managed care database. Study patients were 65+
      years of age with paid claims during 2004. The COPD cohort comprised patients
      with 1+ inpatient/ER claims or 2+ outpatient claims (>30 days apart) for COPD
      (ICD-9-CM codes 491.xx, 492.x, 496). The comparison cohort included patients
      without COPD matched 3:1 to the COPD cohort on age, sex, enrollment months, and
      Medicare plan. Excess costs of COPD were estimated as the difference in overall
      health plan payments between the two cohorts during 2004. Attributable costs were
      calculated using medical claims with listed diagnoses of COPD or other
      respiratory-related conditions and pharmacy claims for respiratory medications.
      RESULTS: A total of 8370 patients were included in the COPD cohort and were
      matched to 25,110 comparison cohort patients. For both groups, mean (SD) age was
      78 (8) years, 54% were female, and duration of eligibility was 11 (2) months.
      COPD patients were more likely to utilize healthcare services and had excess
      total healthcare costs about $20,500 higher (P<0.0001) than the comparison
      cohort. Comorbidities were high in the COPD cohort, accounting for 46% of the
      observed excess cost. The attributable cost of COPD averaged about $6,300; other
      respiratory-related costs averaged about $4,400. CONCLUSION: In this U.S.
      Medicare managed care population, COPD posed a substantial burden in terms of
      both respiratory-related and total healthcare costs. A comparison of these cost
      of-illness estimates to those for elderly COPD patients in other countries would
      be of great interest, given the increasing age of populations in most Western
      countries.

PMID- 18620853
TI  - Long-term mortality follow-up of the ISOLDE participants: causes of death during
      13 years after trial completion.
AB  - The Inhaled Steroids in Obstructive Lung Disease (ISOLDE) study was a trial that
      randomised 752 patients with moderate to severe COPD to fluticasone propionate
      1000 mcg/day or placebo for three years. We aimed to examine the causes of death
      of the ISOLDE participants after the original three up to 13 years post
      randomisation. Death certificates were obtained either from the NHS Strategic
      Tracing Service or from the Office of National statistics. Deaths were classified
      according to the trial protocol. In the subsample of 375 participants from the
      seven ISOLDE original centers where complete extended follow-up was conducted,
      the factors associated with observed higher mortality (p<0.05) were male gender,
      older age and more severe COPD. Causes of death were; 107 (52%) respiratory, 38
      (18%) cardiac, 29 (14%) lung cancer, 16 (8%) other cancer and 16 (8%) other
      causes. The percentage of respiratory-related deaths increased during the follow
      up period; from 46% within the three-year trial, to 48% after 3-6 years, 57%
      after 6-9 years, and 60% after 9-13 years of follow-up (p for trend<0.05). We
      conclude that participants' survival is poor (only 44% in the 13 years after the
      ISOLDE trial), and that respiratory-related illnesses were the most frequent
      causes of death in patients with moderate to severe COPD.

PMID- 18620854
TI  - Urban observatories opportunities for environmental monitoring: solid wastes.
AB  - Towns concentrate around 50% of world-wide population and the trend is oriented
      to underscore an urban profile of population. In addition, towns have become
      important for their economic contribution to the Gross Internal Product. The
      negative side of towns is the environmental and social impacts as a result of
      productive and domestic activities, besides the lack of available data. In order
      to overcome these shortcomings, the United Nations has established a project of
      urban monitoring throughout the Global Network of Urban Observatories; Mexico
      joined the project in 2005. The Local Urban Observatory of Mexicali has the task
      to produce information about cities that is useful to design public policies.
      Some of this information deals with a set of environmental indicators in the
      United Nations Habitat Agenda, which includes solid wastes. Therefore, this paper
      deals with two main topics; firstly, from the Habitat Agenda, a comparative urban
      analysis of waste production and coverage of domestic waste collection services;
      secondly, from the Local Agenda, the identification and ranking of environmental
      problems according to public perception coming from people involved in the
      municipal planning and decision making process. Results will be used to develop
      local indicators and public environmental policies.

PMID- 18620855
TI  - Cerebral metastases in non-seminomatous germ cell tumour patients undergoing
      primary high-dose chemotherapy.
AB  - BACKGROUND: Retrospective analysis of characteristics and outcome of germ cell
      tumour (GCT) patients with cerebral metastases (CM) undergoing high-dose
      chemotherapy (HD-CTX) or relapsing with CM. PATIENTS AND METHODS: Patients
      initially presenting with CM (N=50 pts) or at first relapse (n=19 pts) after
      primary HD-CTX (434 pts) were analysed. RESULTS: Patients with primary CM (N=50)
      had elevated ss-human chorion gonadotropin (ss-HCG) in 88% and lung metastases in
      90%. Eighty six percent responded to HD-CTX and 40% underwent CNS radiotherapy.
      Forty four percent achieved long-term survival after primary and 16% after
      salvage treatment (60% in total). All patients relapsing with CM (n=19) presented
      initially with ss-HCG-elevation and pulmonary metastases. Treatment consisted of
      CTX in 78%, irradiation in 90% and surgery in 63%. Twenty six percent achieved
      long-term survival. CONCLUSION: An interdisciplinary approach of HD-CTX,
      radiotherapy and surgery leads to long-term survival in 60% of patients with CM
      at initial diagnosis and 26% relapsing with CM.

PMID- 18620856
TI  - Synthesis and biological evaluation of a focused library of beauveriolides.
AB  - Fungal beauveriolide III (1b), discovered as an inhibitor of lipid droplet
      accumulation in mouse macrophages and showing antiatherogenic activity in mouse
      model, consists of l-Phe, l-Ala, d-allo-Ile, and (3S, 4S)-3-hydroxy-4
      methyloctanoic acid moieties. A combinatorial library of beauveriolide analogues
      focusing on l-Ala and d-allo-Ile of 1b was synthesized by combinatorial
      synthesis. Among them, d-Ala analogues consisting of A{2} improved their
      solubility, while those with 7{1,3,2},7{2,3,1}, and 7{2,3,2} were 20 times more
      potent than 1b.

PMID- 18620857
TI  - Synthesis of some novel imidazole-based dicationic carbazolophanes as potential
      antibacterials.
AB  - Synthesis of fluorescent imidazole-based dicationic carbazolophanes incorporating
      various spacer units is described. Interestingly, the cyclophanes 2a and 5a
      incorporating a pyridine moiety exhibited superior antibacterial activity against
      most of the pathogenic bacteria in the tested concentrations as compared to the
      other cyclophanes as well as the test control, benzalkonium chloride (BAC),
      cetylpyridinium chloride (CPC) and tetracycline.

PMID- 18620859
TI  - Mechanisms of procentriole formation.
AB  - The centrosome comprises a pair of centrioles and associated pericentriolar
      material, and it is the principal microtubule-organizing centre of most animal
      cells. Like the genetic material, the centrosome is duplicated once and only once
      during the cell cycle. Despite the fact that both doubling events are crucial for
      genome integrity, the understanding of the mechanisms governing centrosome
      duplication has lagged behind the fuller knowledge of DNA replication. Here, we
      review recent findings that provide important mechanistic insights into how a
      single procentriole forms next to each centriole once per cell cycle, thus
      ensuring that one centrosome becomes two.

PMID- 18620858
TI  - Using plasma membrane nanoclusters to build better signaling circuits.
AB  - Cellular signaling pathways do not simply transmit data; they integrate and
      process signals to operate as switches, oscillators, logic gates, memory modules
      and many other types of control system. These complex processing capabilities
      enable cells to respond appropriately to the myriad of external cues that direct
      growth and development. The idea that crosstalk and feedback loops are used as
      control systems in biological signaling networks is well established. Signaling
      networks are also subject to exquisite spatial regulation, yet how spatial
      control modulates signal outputs is less well understood. Here, we explore the
      spatial organization of two different signal transduction circuits: receptor
      tyrosine kinase activation of the mitogen-activated protein kinase module; and
      glycosylphosphatidylinositol-anchored receptor activation of phospholipase C.
      With regards to these pathways, recent results have refocused attention on the
      crucial role of lipid rafts and plasma membrane nanodomains in signal
      transmission. We identify common design principals that highlight how the spatial
      organization of signal transduction circuits can be used as a fundamental control
      mechanism to modulate system outputs in vivo.

PMID- 18620861
TI  - The coordination of upper and lower limb movements during gait in healthy and
      stroke individuals.
AB  - Human walking involves coordinated movements of all four limbs. The benefits of
      incorporating arm movements in gait rehabilitation are not known and difficult to
      investigate in patient populations with poor balance and reduced walking
      capacity. This study assessed the effect of supported (SUP) versus unsupported
      (UNSUP) arm movements on the coordination patterns present during walking in
      individuals with and without a stroke. Ten high functioning stroke subjects and
      10 healthy subjects walked on a treadmill while swinging their arms naturally,
      and while holding onto handles that were either fixed in place or allowed to
      slide along horizontal handrails. Full-body kinematics were recorded, and arm-leg
      coordination was quantified using relative phase index, mean relative phase, and
      cross-correlation of hip and shoulder angle time series. No differences were
      observed in any measures of coordination between healthy and stroke subjects,
      indicating that the ability to coordinate arm and leg movements during walking
      remains preserved in high functioning stroke individuals. Coordination patterns
      were also unaffected by the use of sliding handrails, suggesting that this
      paradigm may be a suitable surrogate for natural arm movements if individuals are
      unable to walk without an external support. Stroke subjects were able to perform
      arm movements at a faster walking speed when using the handles than they were
      able to achieve without the handles, indicating that this paradigm may be useful
      in encouraging arm movements during gait rehabilitation.

PMID- 18620862
TI  - Experimental study of the influence of the m. tibialis anterior on the walk-to
      run transition by means of a powered ankle-foot exoskeleton.
AB  - The purpose of this study was to investigate the role of the tibialis anterior
      (TA) in the walk-to-run transition (WRT) by means of an experimental manipulation
      that allows increasing or decreasing muscular effort of the TA around heel
      contact. Eight subjects performed five WRTs on an accelerating treadmill wearing
      a powered ankle-foot exoskeleton. There was a trend towards a lower WRT-speed in
      the condition in which the TA was resisted (2.06+/-0.09 m s(-1)) than in the
      control condition (2.10+/-0.10 m s(-1)). This finding could not be extrapolated
      in the opposite direction, as there was no significant difference between the
      assist and control condition. The TA activation burst around heel contact showed
      a pattern that led to the hypothesis that the TA activation reaches a critical
      level at the fourth last heel contact before the WRT which triggers the WRT. The
      fact that the results comply with previous transition studies emphasises the role
      of the TA as a determinant of the WRT.

PMID- 18620863
TI  - How to quantify knee function after total knee arthroplasty?
AB  - Total knee arthroplasty (TKA) is being undertaken in a younger population than
      before and as a result the functional demands on the knee are likely to be
      increasing. As a consequence, it is important to define quantitative functional
      knee tests that can monitor any increase. A valuable functional knee test has to
      be able to distinguish small differences (selectivity) and has to be independent
      of pain (content validity). In this study, patient-based questionnaires (WOMAC
      and Knee Society score) and performance-based tests (sit-to-stand movement,
      maximal isometric contraction and timed-up-and-go) were used to assess which of
      these tests are selective and valid to measure knee function. Tests were
      considered to be selective if they could discriminate between knee patients and
      healthy control subjects, and to have functional content validity if they were
      relatively independent of pain. Twenty-eight patients were measured 16 months
      after surgery and compared to a healthy control group of 31 subjects. The sit-to
      stand movement and timed-up-and-go test were both selective and functionally
      content valid. The timed-up-and-go test can be used for a quick initial
      assessment of global function and the sit-to-stand movement as a more
      biomechanical instrument identifying how the knee function of the patient is
      affected.

PMID- 18620865
TI  - Therapeutic angiogenesis using naked DNA expressing two isoforms of the
      hepatocyte growth factor in a porcine acute myocardial infarction model.
AB  - OBJECTIVE: We evaluated the potency of therapeutic angiogenesis using
      intramyocardial injection of naked DNA expressing two isoforms of hepatocyte
      growth factor (pCK-HGF-X7) in a porcine myocardial infarction model. METHODS:
      Four weeks after left anterior descending coronary artery ligation, 14 pigs were
      allocated to pCK-Null (negative control, n=7) or pCK-HGF-X7 (n=7) treatment
      groups. Gated myocardial single photon emission computed tomography was performed
      4 and 8 weeks following coronary ligation. The effect of pCK-HGF-X7 on capillary
      density in the gene-injected myocardium was examined by histological analysis
      using alkaline phosphatase staining. RESULTS: Segmental myocardial perfusion of
      the underperfused area (< or =70%) from coronary ligation increased in the pCK
      HGF-X7 group (p=0.051), without significant differences in changes over time
      between the two groups (p=0.54). Systolic wall thickening (p=0.001), left
      ventricular end-diastolic (p=0.045) and end-systolic volumes (p=0.009), and left
      ventricular ejection fraction (p=0.041) changed in both groups without
      significant differences in changes over time between the two groups. The increase
      in the left stoke volume was higher in the pCK-HGF-X7 group than in the pCK-Null
      group (p=0.008). Histological analysis showed that capillary density was
      significantly higher in the pCK-HGF-X7 group than the pCK-Null group (p<0.001).
      CONCLUSION: Intramyocardial injection of pCK-HGF-X7 induced significant
      angiogenesis at infarct-border zone, and increased the left ventricular stroke
      volume probably caused by reverse remodeling process.

PMID- 18620864
TI  - Novel inhibitors of anthrax edema factor.
AB  - Several pathogenic bacteria produce adenylyl cyclase toxins, such as the edema
      factor (EF) of Bacillus anthracis. These disturb cellular metabolism by
      catalyzing production of excessive amounts of the regulatory molecule cAMP. Here,
      a structure-based method, where a 3D-pharmacophore that fit the active site of EF
      was constructed from fragments, was used to identify non-nucleotide inhibitors of
      EF. A library of small molecule fragments was docked to the EF-active site in
      existing crystal structures, and those with the highest HINT scores were
      assembled into a 3D-pharmacophore. About 10,000 compounds, from over 2.7 million
      compounds in the ZINC database, had a similar molecular framework. These were
      ranked according to their docking scores, using methodology that was shown to
      achieve maximum accuracy (i.e., how well the docked position matched the
      experimentally determined site for ATP analogues in crystal structures of the
      complex). Finally, 19 diverse compounds with the best AutoDock binding/docking
      scores were assayed in a cell-based assay for their ability to reduce cAMP
      secretion induced by EF. Four of the test compounds, from different structural
      groups, inhibited in the low micromolar range. One of these has a core structure
      common to phosphatase inhibitors previously identified by high-throughput assays
      of a diversity library. Thus, the fragment-based pharmacophore identified a small
      number of diverse compounds for assay, and greatly enhanced the selection process
      of advanced lead compounds for combinatorial design.

PMID- 18620866
TI  - Three-dimensional concentration mapping of gases using a portable mass
      spectrometer system.
AB  - The visualization of hazardous gaseous emissions at volcanoes using in-situ mass
      spectrometry (MS) is a key step towards a better comprehension of the geophysical
      phenomena surrounding eruptive activity. In-situ data consisting of helium,
      carbon dioxide, sulfur dioxide, and other gas species, were acquired with a
      quadrupole based MS system. Global position systems (GPS) and MS data were
      plotted on ground imagery, topography, and remote sensing data collected by a
      host of instruments during the second Costa Rica Airborne Research and Technology
      Applications (CARTA) mission. This combination of gas and imaging data allowed
      three-dimensional (3D) visualization of the volcanic plume and the mapping of gas
      concentration at several volcanic structures and urban areas. This combined set
      of data has demonstrated a better tool to assess hazardous conditions by
      visualizing and modeling of possible scenarios of volcanic activity. The MS
      system is used for in-situ measurement of 3D gas concentrations at different
      volcanic locations with three different transportation platforms: aircraft, auto,
      and hand-carried. The demonstration for urban contamination mapping is also
      presented as another possible use for the MS system.

PMID- 18620867
TI  - Peptide and protein quantification using iTRAQ with electron transfer
      dissociation.
AB  - Electron transfer dissociation (ETD) has become increasingly used in proteomic
      analyses due to its complementarity to collision-activated dissociation (CAD) and
      its ability to sequence peptides with post-translation modifications (PTMs). It
      was previously unknown, however, whether ETD would be compatible with a commonly
      employed quantification technique, isobaric tags for relative and absolute
      quantification (iTRAQ), since the fragmentation mechanisms and pathways of ETD
      differ significantly from CAD. We demonstrate here that ETD of iTRAQ labeled
      peptides produces c- and z-type fragment ions as well as reporter ions that are
      unique from those produced by CAD. Exact molecular formulas of product ions were
      determined by ETD fragmentation of iTRAQ-labeled synthetic peptides followed by
      high mass accuracy orbitrap mass analysis. These experiments revealed that ETD
      cleavage of the N-C(alpha) bond of the iTRAQ tag results in fragment ions that
      could be used for quantification. Synthetic peptide work demonstrates that these
      fragment ions provide up to three channels of quantification and that the quality
      is similar to that provided by beam-type CAD. Protein standards were used to
      evaluate peptide and protein quantification of iTRAQ labeling in conjunction with
      ETD, beam-type CAD, and pulsed Q dissociation (PQD) on a hybrid ion trap-orbitrap
      mass spectrometer. For reporter ion intensities above a certain threshold all
      three strategies provided reliable peptide quantification (average error <10%).
      Approximately 36%, 8%, and 16% of scans identified fall below this threshold for
      ETD, HCD, and PQD, respectively. At the protein level, average errors were 2.3%,
      1.7%, and 3.6% for ETD, HCD, and PQD, respectively.

PMID- 18620869
TI  - Immunolocalization of matrix proteins in nacre lamellae and their in vivo effects
      on aragonitic tablet growth.
AB  - How matrix proteins precisely control the growth of nacre lamellae is an open
      question in biomineralization research. Using the antibodies against matrix
      proteins for immunolabeling and in vivo experiments, we investigate the
      structural and functional roles of EDTA-soluble matrix (SM) and EDTA-insoluble
      matrix (ISM) proteins in nacre biomineralization of the pearl oyster Pinctada
      fucata. Immunolabeling reveals that a SM protein, nacrein, distributes within
      aragonitic tablets and intertabular matrix. An ISM protein, which we named P43,
      has been specifically recognized by polyclonal antibodies raised against the
      recombinant protein of P. fucata bone morphogenetic protein 2 in immunoblot
      analysis. Immunolabeling indicates that P43 is localized to interlamellar sheet,
      and also embedded within aragonitic tablets. Although nacrein and P43 both
      distribute within aragonitic tablets, they function differently in aragonitic
      tablet growth. When nacrein is suppressed by the antibodies against it in vivo,
      crystal overgrowth occurs, indicating that this SM protein is a negative
      regulator in aragonitic tablet growth. When P43 is suppressed in vivo, the organo
      mineral assemblage is disrupted, suggesting that P43 is a framework matrix. Taken
      together, SM and ISM proteins are indispensable factors for the growth of nacre
      lamellae, controlling crystal growth and constructing the framework of aragonitic
      tablets.

PMID- 18620871
TI  - The systematic affinity of the enigmatic Lamprolia victoriae (Aves:
      Passeriformes)--an example of avian dispersal between New Guinea and Fiji over
      Miocene intermittent land bridges?

PMID- 18620868
TI  - The lymph node in HIV pathogenesis.
AB  - Since the earliest days of the AIDS epidemic, clinicians and researchers have
      recognized the importance of lymphoid tissue both in the clinical manifestations
      of disease and in its pathogenesis. Generalized lymphadenopathy was one of the
      earliest harbingers of AIDS in the United States and over the past 27 years an
      increasing body of evidence has implicated the lymphoid organs as central to the
      pathogenesis of immune deficiency in chronic HIV-1 infection. In this essay, we
      will review some of the data that have been accumulated and propose a testable
      model that may reconcile them.

PMID- 18620870
TI  - Molecular phylogeny and population structure of the codling moth (Cydia
      pomonella) in Central Europe: I. Ancient clade splitting revealed by
      mitochondrial haplotype markers.
AB  - The codling moth (Cydia pomonella L., Tortricidae, Lepidoptera) is an important
      pest of pome fruit with global distribution. It has adapted successfully to
      different habitats by forming various ecotypes and populations, often termed
      strains, which differ among each other in several morphological, developmental,
      and physiological features. Many strains of Cydia pomonella have developed
      resistance against a broad range of chemically different pesticides. Obviously,
      pesticide-resistant strains must have a genetic basis inherent to the gene pool
      of codling moth populations, and this deserves our particular attention. The
      primary intention of the present study was to contribute novel information
      regarding the evolutionary phylogeny and phylogeography of codling moth
      populations in Central Europe. In addition, we aimed at testing the hypothesis
      that differential biological traits and response patterns towards pesticides in
      codling moth populations may be reflected at a mitochondrial DNA level. In
      particular, we wanted to test if pesticide resistance in codling moths is
      associated repeatedly and independently with more than one mitochondrial
      haplotype. To this end, we analyzed mitochondrial DNA and constructed
      phylogenetic trees based on three mitochondrial genes: cytochrome oxidase I
      (COI), the A+T-rich region of the control region (CR), and the nicotinamide
      adenine dinucleotide dehydrogenase subunit 5 (ND5). The results indicate that
      Central European populations of Cydia pomonella are clearly divided in two
      ancient clades. As shown by means of a molecular clock approach, the splitting of
      the two clades can be dated to a time period between the lower and middle
      Pleistocene, about 1.29-0.20 million years ago. It is assumed that the cyclic
      changes of warm and cold periods during Pleistocene may have lead to the
      geographic separation of codling moth populations due to glaciation, giving rise
      to the formation of the two separate refugial clades, as already shown for many
      other European animal species. Due to their inclination towards developing novel
      detoxification gene variants, codling moth individuals from both clades
      independently and multifariously may have developed pesticide resistance, and
      this process may be ongoing. During their more recent evolutionary history,
      natural events such as the gradual disappearance of climate-specific geographic
      barriers, as well as human-aided dispersal in recent historic times, may have
      allowed codling moth haplotypes from the original clades to interbreed and
      completely merge again, creating a globally successful insect species with a gene
      pool capable of responding to novel selective challenges by rapid adaptation.

PMID- 18620872
TI  - Phylogenetic utility of 141 low-copy nuclear regions in taxa at different
      taxonomic levels in two distantly related families of rosids.
AB  - Angiosperm systematics has progressed to the point where it is now expected that
      multiple, independent markers be used in phylogenetic studies. Universal primers
      for amplifying informative regions of the chloroplast genome are readily
      available, but in the faster-evolving nuclear genome it is challenging to
      discover priming sites that are conserved across distantly related taxa. With
      goals including the identification of informative markers in rosids, and perhaps
      other angiosperms, we screened 141 nuclear primer combinations for phylogenetic
      utility in two distinct groups of rosids at different taxonomic levels-Psiguria
      (Cucurbitaceae) and Geraniaceae. We discovered three phylogenetically informative
      regions in Psiguria and two in Geraniaceae, but none that were useful in both
      groups. Extending beyond rosids, we combined our findings with those of another
      recent effort testing these primer pairs in Asteraceae, Brassicaceae, and
      Orchidaceae. From this comparison, we identified 32 primer combinations that
      amplified regions in representative species of at least two of the five distantly
      related angiosperm families, giving some prior indication about phylogenetic
      usefulness of these markers in other flowering plants. This reduced set of primer
      pairs for amplifying low-copy nuclear markers along with a recommended
      experimental strategy provide a framework for identifying phylogenetically
      informative regions in angiosperms.

PMID- 18620873
TI  - Heart rate variability in patients with frontal lobe epilepsy.
AB  - OBJECTIVE: To identify autonomic dysregulation in frontal lobe epilepsy (FLE).
      METHODS: We studied 14 male and 11 female subjects with FLE and an equal number
      of matched healthy control subjects. Lead I electrocardiograms were obtained for
      5 min in the interictal state during daytime. Frequency-domain analysis of heart
      rate variability was performed and the data subsequently converted to heart rate
      interval and high frequency (HF; 0.15-0.45 Hz) power which representing vagal or
      parasympathetic regulation, as well as low frequency (LF; 0.04-0.15 Hz) power and
      LF/(HF+LF) expressed in normalized units (LF%) (considered to mirror sympathetic
      regulation). Differences in data between groups were compared using t-test.
      RESULTS: The epilepsy group had a lower mean heart rate interval and a lower high
      frequency power. CONCLUSIONS: Patients with FLE have interictally faster heart
      rates, attributed to lower parasympathetic drive, which may contribute to the
      higher incidence of sudden death that is seen in this group of patients. This
      suggests that the mechanism of decreased HRV in patients with FLE is probably
      different from that in patients with temporal lobe epilepsy.

PMID- 18620874
TI  - Validation of the Dutch version of the Hip disability and Osteoarthritis Outcome
      Score.

PMID- 18620875
TI  - Relationship between nicotinic receptors and cognitive function in early
      Alzheimer's disease: a 2-[18F]fluoro-A-85380 PET study.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order
      cognitive processes. Post-mortem studies suggest reductions in nAChRs
      (particularly the alpha(4)beta(2) subtype) with ageing and in Alzheimer's disease
      (AD). This study aimed to; (1) quantify nAChR distribution in vivo with 2
      [18F]fluoro-A-85380 (2-FA) in 15 early AD patients compared to 14 age-matched,
      healthy controls (HC) and (2) correlate nAChR distribution with cognitive
      performance in both groups. All participants were non-smokers and underwent
      cognitive testing along with a dynamic PET scan after injection of 200 MBq of 2
      FA. Brain regional 2-FA binding was assessed through a simplified estimation of
      Distribution Volume (DV(S)). The AD group differed significantly from HC on all
      cognitive measures employed, with impairments on measures of attention, working
      memory, language, executive function, visuospatial ability, verbal learning and
      verbal memory (p<.05). Contrary to post-mortem data this study found no evidence
      of in vivo nAChR loss in early AD despite significant cognitive impairment.
      Furthermore, no correlation between nAChR and cognitive performance was found for
      either group. The findings of the current study suggest preservation of nAChRs
      early in AD supporting previous studies. It is possible that while the clinical 2
      FA PET method described here may be insensitive in detecting changes in early AD,
      such changes may be detected in more advanced stages of the illness.

PMID- 18620876
TI  - Will carotid angioplasty become the preferred alternative to staged or
      synchronous carotid endarterectomy in patients undergoing cardiac surgery?
AB  - In the absence of randomized trials, the optimal management of patients who
      present with concomitant carotid and coronary artery disease remains an enduring
      controversy, with much of the debate revolving around whether staged or
      synchronous carotid endarterectomy (CEA) will reduce peri-operative morbidity and
      mortality after cardiac surgery. Although encouraging results have been reported
      using either strategy, there remains no consensus as to which is preferable. More
      recently, however, carotid artery angioplasty with stenting (CAS) has emerged as
      a potential alternative to CEA. In 'high-risk for CEA' patients, CAS has shown
      comparable short and long-term outcome rates to CEA. Accordingly, CAS followed by
      cardiac surgery could offer a less invasive (and safer) therapeutic option in
      cardiac patients. This paper reviews the evidence to date supporting the use of
      CAS+CABG, while highlighting potential situations where such a strategy might be
      harmful. In particular, it will focus on how the need for dual antiplatelet
      therapy after CAS can be balanced with avoiding unnecessary bleeding
      complications after cardiac surgery.

PMID- 18620877
TI  - Mycobacteriosis in fishes: a review.
AB  - Mycobacterium species have long been recognised as a significant source of
      morbidity and mortality in finfish aquaculture, as well as in wild finfishes.
      Mycobacteria infecting fishes also include zoonotic pathogens that can cause
      protracted illness, especially in immunocompromised individuals. Several basic
      aspects of mycobacterial pathobiology in aquatic animals remain poorly
      understood, although a number of important recent developments have been made,
      especially with respect to identification of novel Mycobacterium spp. infecting
      fishes and a new group of mycobacteria closely related to the human pathogen
      Mycobacterium ulcerans. This review will encompass important aspects of
      mycobacterial disease in fishes, discuss recent research including studies of
      mycobacteriosis in striped bass (Morone saxatilis) of Chesapeake Bay, USA, and
      suggest directions for future work.

PMID- 18620878
TI  - Incidence and treatment of inadequate postovulatory progesterone concentrations
      in repeat breeder cows.
AB  - The incidence of low day 5 milk progesterone in dairy cows has been investigated
      and the efficacy of treating the problem assessed. The incidence of inadequate
      milk progesterone (empirically defined as <3ng/mL) in repeat breeder cows was 34%
      compared with 11.4% in first insemination cows. Treatment with an intravaginal
      progesterone device for 7 days starting from day 5 or 6 did not improve pregnancy
      rate. Treatment with 1500 iu human chorionic gonadotrophin (hCG) on day 5 gave an
      increase in pregnancy rate that was dependent on initial progesterone
      concentration and significant (P<0.05) in multiparous but not primiparous cows.
      While the incidence of inadequate day 5 progesterone was high in repeat breeder
      cows, it was responsive to hCG treatment, although only in multiparous and not
      primiparous animals.

PMID- 18620879
TI  - Pediatric canalicular tear repairs--revisiting the pigtail probe.
AB  - Repairing canalicular lacerations can be complicated by difficulty in identifying
      and intubating the proximal injured system, retrieving stents in the nose, and
      repairing canalicular epithelium. We describe a hybrid method of repair that
      alleviates these challenges by the use of an eyelet-type pediatric pigtail probe
      and a self-threading monocanalicular stent. The pigtail probe is inserted through
      the intact punctum and canaliculus on the injured eyelid and rotated to identify
      the medial edge of the torn canaliculus. The stent is threaded through the
      injured punctum and pigtail probe, drawn back out the intact puncta, and cut
      flush. The eyelid is repaired without direct suturing of the canaliculus. When we
      applying this technique to 10 children, we successfully intubated the injured
      system without complication, and all children had good anatomic and clinical
      results, with negative dye disappearance tests.

PMID- 18620880
TI  - Ocular involvement after subgaleal hematoma.
AB  - Subgaleal hemorrhage (SGH) is a known complication of both major and minor
      childhood head trauma. Rarely, it can be associated with intraorbital hemorrhage
      and ocular compromise. We report a child who presented with SGH and later
      developed orbital hemorrhages bilaterally with loss of vision necessitating
      surgical intervention. We also review the literature for this condition.

PMID- 18620881
TI  - Morning glory disk anomaly with ipsilateral capillary hemangioma, agenesis of the
      internal carotid artery, and Horner syndrome: a variant of PHACES syndrome?
AB  - We describe a 6-week-old girl with a right upper lid capillary hemangioma,
      ipsilateral morning glory disk anomaly, microphthalmos, Mittendorf dot, and
      Horner syndrome. The ipsilateral internal carotid artery was also found to be
      absent. To our knowledge, this is the first patient to be reported with this
      group of findings. We suggest that this represents an overlap between morning
      glory disk and intracranial vascular abnormalities, a recognized association, and
      PHACES syndrome (posterior fossa malformations, hemangiomas, arterial anomalies,
      cardiac defects, eye, and sternal abnormalities). We discuss the common
      embryological basis for these abnormalities, which point to a widespread but
      highly variable disorder of mesodermal differentiation.

PMID- 18620882
TI  - Functional and structural characterization of PKA-mediated pHi gating of ROMK1
      channels.
AB  - Hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS) is a severe
      salt-losing renal tubular disorder and results from the mutation of renal outer
      medullary K(+) (ROMK1) channels. The aberrant ROMK1 function induces alterations
      in intracellular pH (pH(i)) gating under physiological conditions. We investigate
      the role of protein kinase A (PKA) in the pH(i) gating of ROMK1 channels. Using
      giant patch clamp with Xenopus oocytes expressing wild-type and mutant ROMK1
      channels, PKA-mediated phosphorylation decreased the sensitivity of ROMK1
      channels to pH(i). A homology model of ROMK1 reveals that a PKA phosphorylation
      site (S219) is spatially juxtaposed to the phosphatidylinositol 4,5-bisphosphate
      (PIP(2)) binding residues (R188, R217, and K218). Molecular dynamics simulations
      suggest a stable transition state, in which the shortening of distance between
      S219 and R217 and the movement of K218 towards the membrane after the PKA
      phosphorylation can be observed. Such conformational change may bring the PIP(2)
      binding residues (K218) more accessible to the membrane-bound PIP(2). In
      addition, PIP(2) dose-dependently reactivates the acidification-induced rundown
      channels only when ROMK1 channels have been phosphorylated by PKA. This implies a
      sequence regulatory episode reflecting the role of PIP(2) in the pH(i) gating of
      ROMK1 channels by PKA-mediated phosphorylation. Our results provide new insights
      into the molecular mechanisms underlying the ROMK1 channel regulation associated
      with HPS/aBS.

PMID- 18620884
TI  - A fatal case of pacemaker lead endocarditis caused by Mucor spp.

PMID- 18620883
TI  - How amantadine and rimantadine inhibit proton transport in the M2 protein
      channel.
AB  - To understand how antiviral drugs inhibit the replication of influenza A virus
      via the M2 ion channel, molecular dynamics simulations have been applied to the
      six possible protonation states of the M2 ion channel in free form and its
      complexes with two commercial drugs in a fully hydrated lipid bilayer. Among the
      six different states of free M2 tetramer, water density was present in the pore
      of the systems with mono-protonated, di-protonated at adjacent position, tri
      protonated and tetra-protonated systems. In the presence of inhibitor, water
      density in the channel was considerably better reduced by rimantadine than
      amantadine, agreed well with the experimental IC(50) values. With the
      preferential position and orientation of the two drugs in all states, two
      mechanisms of action, where the drug binds to the opening pore and the histidine
      gate, were clearly explained, i.e., (i) inhibitor was detected to localize
      slightly closer to the histidine gate and can facilitate the orientation of His37
      imidazole rings to lie in the close conformation and (ii) inhibitor acts as a
      blocker, binding at almost above the opening pore and interacts slightly with the
      three pore-lining residues, Leu26, Ala30 and Ser31. Here, the inhibitors were
      found to bind very weakly to the channel due to their allosteric hindrance while
      theirs side chains were strongly solvated.

PMID- 18620885
TI  - [Why defer blood donor candidates because of an exposure risk to Chagas
      disease?].
AB  - Various infectious agents can be transmitted by blood exposure, which comprises
      of transfusion, of which hemoparasites that are commonly absent from European
      countries but that can have infected blood donor candidates born, raised or
      having been living in the Tropics. Among those hemoparasites is Trypanosoma
      cruzi, responsible for Chagas disease. T. cruzi is responsible for acute post
      transfusion infections every year in endemic areas (South America) and also, more
      incidently, in North America. There are situations which expose European blood
      donors to this risk and the present essay discusses arguments which have now been
      taken into consideration by certain transfusion systems such as the French one.

PMID- 18620886
TI  - Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated
      rabbits.
AB  - OBJECTIVES: To investigate in vivo effects of lovastatin on inhibition of
      adipogenesis, an important mechanism of steroid-induced osteonecrosis, and on
      prevention of occurrence of steroid-induced osteonecrosis in rabbits. METHODS:
      Fifty-four rabbits were intramuscularly injected once with 20mg/kg of
      methylprednisolone acetate (MPSL). Then, they were divided into two groups:
      lovastatin was given in Group I and placebo was given in Group II. And another 16
      rabbits were injected with physiologic saline (PS) as a control (Group III).
      Hematological examination was performed for serum lipid levels. Both the femora
      and the humeri were histopathologically examined for the presence of
      osteonecrosis before the injection and 1, 2, 4 and 12 weeks after the injection.
      RESULTS: The serum lipid levels were significantly higher in Group II than in
      Groups I and III 1, 2 and 4 weeks after the injection. The incidence of
      osteonecrosis was significantly higher in Group II (69%) than in Group I (36%)
      and Group III (0%). Pathological examination showed less serious adipogenesis and
      bone death in Group I than in Group II. The size and area of the fat cells in the
      bone marrow were significantly smaller in Group I (47.5+/-1.3 microm, 25%) and
      Group III (41.7+/-1.6 microm, 12%) than in Group II (59.8+/-6.3 microm, 51%) (P<
      0.001). CONCLUSION: Lovastatin can prevent development of steroid-induced
      osteonecrosis in rabbits by inhibiting adipogenesis. Future evaluation on the
      effectiveness of lovastatin in the clinical practice is still necessary.

PMID- 18620887
TI  - "Air pollution is bad for my health": Hungarian children's knowledge of the role
      of environment in health and disease.
AB  - This study describes beliefs and knowledge of harmful environmental factors and
      environment-borne disease in 9- to 11-year-olds' (N=448) using the "draw-and
      write" technique as a method of data collection. Most respondents described the
      man-made environmental risks (such as car transportation or noise pollution) as
      direct effects; however, in their interpretations, lifestyle (e.g., smoking) and
      other effects (e.g., pollen pollution) also received considerable emphasis.
      Although many did not describe a specific disease as environment-borne diseases,
      the most mentioned among the children were infectious diseases followed by
      allergy. The results of this study draw the attention to the relationship between
      health and environmental consciousness.

PMID- 18620889
TI  - The impact of lymphovascular invasion on survival in oral carcinoma.
AB  - Data was retrospectively analysed on 72 consecutive patients treated primarily
      with resection and concomitant neck dissection for intraoral carcinomas. Twenty
      prognostic variables were assessed by univariate analysis to assess their
      influence on survival. Seven variables were significant at the 5% level. Survival
      was negatively influenced by six tumour related factors, increasing T stage
      (P=0.039), increasing N stage (P=0.004), greater than two nodes histologically
      positive nodal disease (P=0.017), tumour size > 4 cm (P=0.022), residual disease
      at the primary site (P=0.012), extracapsular nodal spread (P=0.01) and the one
      treatment related factor analysed, adjuvant radiotherapy (P=0.039). Subsequent
      multivariate analysis was performed via the cox stepwise regression method to
      assess the influence on survival of all factors which achieved significance at
      the 20% level. There were only two variables which made a significant difference
      (P<0.05) to the multivariate model. The presence of lymphovascular invasion
      (P=0.015) and histological evidence of mandibular invasion (P=0.047).
      Lymphovascular invasion appeared in the final model despite not achieving
      statistical significance at the 5% level on univariate analysis. A final cox
      survival model was constructed. The relative risk of death for those with
      cervical metastases (N2 and above) at diagnosis was 3.74 (P=0.005). The addition
      of lymphovascular invasion to the cox model revealed an increase in the relative
      risk of death in the presence of lymphovascular invasion of 2.99 (P=0.015).
      Patients with nodal negative disease and one single node positive provided the
      baseline risk as there was no significant difference between these two groups.
      The presence of histological evidence of lymphovascular invasion in oral
      carcinoma surgical specimens has a significant impact on survival outcome in oral
      carcinoma patients.

PMID- 18620890
TI  - The submental island flap for reconstruction of intraoral defects in oral cancer
      patients.
AB  - The submental artery island flap (SIF) is gaining acceptance as a simple and
      reliable option in selected oral oncologic reconstructions. The present study
      aims to assess the usefulness of submental artery flap in oral reconstruction
      with respect to flap reliability, cosmesis, function, donor site morbidity and
      oncological safety. Thirty (30) patients who underwent ablative surgery and
      reconstruction using the submental artery island flap for oral cancer at Regional
      Cancer Centre, Trivandrum, India, between October 2004 and December 2006 were
      prospectively studied for the flap viability, cosmesis, function (speech and
      swallowing) and locoregional recurrence. The site and stage of the tumour, type
      of resection, management of the neck and the technique of flap transfer were
      recorded and the patients were followed up to assess the status of the flap and
      its donor site and the oncologic outcomes. There were 19 men and 11 women, ages
      of whom ranged from 30 years to 78 years with a mean+/-SD of 53+/-11 years. With
      the exception of one patient who had undergone neck dissection as part of a
      previous surgery, all patients underwent neck dissection or at least a level I
      clearance along with the wide excision of the primary lesion. The follow up
      period ranged from 4 to 25 months with a median of 13.5 months. Six patients
      either recurred locoregionally or had metachronous second primary constituting an
      over all recurrence rate of 20%. The size of the skin paddle ranged from 3 x 3 cm
      to 7 x 6 cm, with a mean size of 4.9 x 4 cm. One total and one partial flap loss
      were observed. One patient had intractable hair growth on the flap even 3 months
      after surgery. Donor site healing was excellent in all cases and the donor site
      scar was well hidden. The long term cosmesis and functions were good in all the
      patients. The submental artery island flap is a simple and reliable option for
      oral cancer reconstruction in carefully selected cases, with acceptable cosmetic
      and functional results and reasonable oncological safety.

PMID- 18620888
TI  - Mechanical modulation of osteochondroprogenitor cell fate.
AB  - Mesenchymal cells are natural tissue builders. They exhibit an extraordinary
      capacity to metamorphize into differentiated cells, using extrinsic spatial and
      temporal inputs and intrinsic algorithms, as well as to build and adapt their own
      habitat. In addition to providing a habitat for osteoprogenitor cells, tissues of
      the skeletal system provide mechanical support and protection for the multiple
      organs of vertebrate organisms. This review examines the role of mechanics on
      determination of cell fate during pre-, peri- and postnatal development of the
      skeleton as well as during tissue genesis and repair in postnatal life. The role
      of cell mechanics is examined and brought into context of intrinsic cues during
      mesenchymal condensation. Remarkable new insights regarding structure function
      relationships in mesenchymal stem cells, and their influence on determination of
      cell fate are integrated in the context of de novo tissue generation and
      postnatal repair. Key differences in the formation of osteogenic and chondrogenic
      condensations are discussed in relation to direct intramembranous and indirect
      endochondral ossification. New approaches are discussed to elucidate and exploit
      extrinsic cues to generate tissues in the laboratory and in the clinic.

PMID- 18620891
TI  - MicroRNA and oral cancer: future perspectives.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the
      post-transcriptional level by degrading or repressing target messenger RNAs
      (mRNA). They are about 22 nucleotides in length and regulate mRNA translation by
      base pairing to partially complementary sites, predominantly in the 3'
      untranslated region (3' UTR) of mRNA. In this review, we discuss miRNA biogenesis
      and function, together with its possible involvement in oral cancer. Despite its
      great importance in normal cell development and diseases, a small number of
      studies have attempted to investigate miRNA in oral cancer. Overexpression of
      oncogenic miRNA may reduce protein products of tumor-suppressor genes. On the
      other hand, loss of tumor-suppressor miRNA expression may cause elevated levels
      of oncogenic protein. One or both of these alterations could represent new
      targets for cancer diagnosis and treatment in the future. Many researchers have
      focused on genetic and epigenetic alterations in oral squamous cell carcinoma
      cells. The emergence of miRNA knowledge, and its potential interactive action
      with such alterations, therefore creates a new understanding of cell
      transformation.

PMID- 18620892
TI  - Prognostic role of pneumonia in supracricoid and supraglottic laryngectomies.
AB  - The goal of this study was to identify host and tumour factors associated with
      postoperative pneumonia (PP) in a selected population of laryngeal cancer
      patients, treated by partial laryngectomy in 20 years at our Institution and to
      assess its potential prognostic impact. Clinical records of 416 consecutive
      patients were retrospectively reviewed. Tobacco consumption, body mass index
      (BMI), previous pulmonary disease, age, sex, preoperative blood gas analysis
      values, tumour stage and type of surgery were tested as potential risk factors
      for PP. Finally, the prognostic impact of these variables, including PP, in terms
      of disease-free and actuarial survival by Kaplan-Meier and Cox analyses were
      evaluated. PP developed in 73 patients (16.8%). We identified two groups of
      patients: 26 patients experienced an early PP within the first 7-9 days after
      surgery, whilst 44 experienced an ab ingestis PP following attempts of oral food
      intake restoration, three patients died for PP related sepsis. At multivariate
      Cox analysis, age older than 60 years and BMI greater than 30 were statistically
      associated with early PP; whereas male gender and laryngectomy with neck
      dissection were statistically related to a higher risk of ab ingestis PP.
      Interestingly, the occurrence of early PP was a negative independent prognostic
      factor for 5-years disease-free and actuarial survival (p=0.049 and p=0.001,
      respectively). The occurrence of early-onset pneumonia in laryngeal cancer
      patients selected for conservative laryngectomies is predictable and associated
      with poor clinical outcome.

PMID- 18620893
TI  - A novel technique for cheek mucosa defect reconstruction using a pedicled buccal
      fat pad and buccinator myomucosal island flap.
AB  - Reconstruction of cheek mucosa defects following tumor resections can be
      approached with several techniques, depending on size of the defect.
      Fasciocutaneous and perforators free flaps are widely employed today for such
      reconstructions. However, small defects or general health of the patient may
      limit their indications. Furthermore, approaching moderate size defects, some
      techniques, like temporalis muscle or fascia pedicled flaps, lead to contracture
      with limitation of mouth opening or trisma, and others, like intraoral local
      flaps, do not provide enough tissue for the reconstructions. In this work the
      authors propose, for reconstructing these kind of defects, the use of a
      buccinator myomucosal island flap and a buccal fat pad pedicled flap association.
      A case is reported and the surgical technique is explained. This new
      reconstructive technique can easily be used for reconstructing moderate-sized
      cheek defects, achieving optimal results: the internal mucosal lining is restored
      in few weeks without any retraction, contracture, of scars on the face limiting
      the aesthetic outcome and mouth opening.

PMID- 18620894
TI  - Umami taste dysfunction in patients receiving radiotherapy for head and neck
      cancer.
AB  - Taste loss is a major cause of morbidity in patients undergoing head and neck
      irradiation. Previous studies have reported the alteration of the four basic
      tastes in patients with head and neck cancer during radiotherapy. However, only a
      few studies have been conducted on the effects of irradiation on the function of
      umami taste, a novel and basic taste recently recognized. In a prospective study,
      52 patients undergoing radical head and neck irradiation were assessed for taste
      loss. Taste ability was measured by the taste threshold for umami quality using
      the whole-mouth taste method in patients before, during, and immediately after
      radiotherapy. Umami taste declined of the 3rd week after the start of
      radiotherapy and improved of the 8th week.

PMID- 18620895
TI  - Prognostic significance of 14-3-3sigma expression in oral squamous cell carcinoma
      (OSCC).
AB  - 14-3-3sigma an intracellular phosphoserine binding protein regulates different
      cellular signalling processes and is involved in cancer development. In this
      study, we examined the expression of 14-3-3sigma and evaluated its clinical
      significance in OSCC. Tumour tissue from 95 OSCC patients was analysed for 14-3
      3sigma and p53 expression, respectively. The correlation of these proteins with
      survival and clinical parameters was assessed. 14-3-3sigma high expression was
      observed in 44.2% of OSCC patients. A significant role of 14-3-3sigma expression
      on survival was shown by Kaplan-Meier analysis. Median survival time was 4.1years
      for patients with 14-3-3sigma low tumours, compared with 1.36years for 14-3
      3sigma high tumours (P=.0021). Subset analysis in patients receiving adjuvant
      chemotherapy showed that the overall survival was significantly decreased in 14-3
      3sigma high tumours than in 14-3-3sigma low tumours (P=.02). p53 expression was
      not significant in univariate analyses. In multivariate regression analysis, 14-3
      3sigma expression emerged as a significant independent parameter (P=.003). These
      results provide evidence that 14-3-3sigma expression is involved in OSCC and, in
      contrast to p53 expression represents a new prognostic marker for OSCC and
      therapy response. Pending validation targeting 14-3-3sigma might also be a new
      opportunity to improve therapy.

PMID- 18620896
TI  - Verrucous carcinoma of the oral cavity: A clinical and pathological study of 101
      cases.
AB  - This paper studies the clinical and pathological predictors of local recurrence
      and disease-free survival (DFS) in patients with oral verrucous carcinoma (OVC)
      treated surgically, through a retrospective chart review. Three hundred and two
      patients with OVC were identified from January 1990 to December 2000, of which,
      101 surgically treated patients who fulfilled our inclusion criteria were
      analyzed. A univariate analysis (UVA) of important prognostic factors, patterns
      of recurrence, and DFS is reported. Seventy-nine patients were male (M:F ratio,
      3.6:1) and the mean age at presentation was 53.9 years (range, 23-90 years). The
      median follow up was 4.61 years (range, 0.51-14.3 years). The incidence of
      tobacco chewing, smoking, and alcohol intake was 77%, 42%, and 10%, respectively.
      Thirty-four patients (33.7%) had either leukoplakia or submucous fibrosis (SMF)
      on oral cavity examination. Early-stage tumors accounted for 39.7%; while 60.4%
      were late-stage tumors. On UVA, tumor location, presence of a premalignant
      lesion, smoking, and positive margins were statistically significant. Sixty-eight
      percent (19/28) recurred locally. The salvage rate for recurrent tumors was 66.7%
      (16/28) with a median post-recurrence survival of 16 months (range, 10-83
      months). The five year DFS with surgical therapy was 77.6%. OVC has an excellent
      prognosis with surgical treatment. The significance of positive margins
      emphasizes the need for adequate surgical resection. Additionally, the presence
      of either leukoplakia or SMF and tumor location in the upper alveolar-palatal
      complex is associated with worse outcomes. Neck dissection, if considered, may be
      limited to a supra-omohyoid neck dissection (SOHND).

PMID- 18620897
TI  - The role of dihydropyrimidine dehydrogenase expression in resistance to 5
      fluorouracil in head and neck squamous cell carcinoma cells.
AB  - 5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs to
      treat cancer patients. However, the presence of drug resistant tumor cells may
      cause a poor response to 5-FU based chemotherapy. Dihydropyrimidine dehydrogenase
      (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and is
      also responsible for the degradation of 5-FU. In this study, we examined whether
      DPD expression affects the cytotoxic activity of 5-FU against head and neck
      squamous cell carcinoma (HNSCC) and the role of DPD in the biological regulation
      of HNSCC. We constitutively expressed the DPD cDNA in a HNSCC cell line. The
      effect of DPD expression on in vitro cell growth, cell cycle and 5-FU
      cytotoxicity was examined. In addition, we also evaluated the association between
      DPD expression and the proliferation of tumor cells in surgical specimens, and
      prognosis of the patients with HNSCC. DPD overexpression decreases the
      cytotoxicity of 5-FU. CDHP, a strong DPD inhibitor, enhances the cytotoxic effect
      of 5-FU in HNSCC cells in vitro. DPD expression level does not effect cell
      proliferation and does not seem to have prognostic value in HNSCC. The present
      results strongly indicate that DPD expression plays an important role in the
      sensitivity of HNSCC to 5-FU chemotherapy, suggesting the possibility of
      personalized chemotherapy including the prediction of response and adverse
      effects.

PMID- 18620898
TI  - Age at diagnosis and prognosis of oral cancer in relation to the patient's
      residential area: experience from a medical center in Taiwan.
AB  - Smoking and betel quid chewing are established risk factors for oral cancer in
      Taiwan. The prevalence of these risk factors in the central county of Changhua
      falls within the middle range nationally, yet the county has the highest
      incidence of oral cancer in Taiwan. The purpose of this study, therefore, was to
      identify if patients' ages and prognoses at diagnosis were related to their place
      of residence and, if so, to explore environmental and geographical factors which
      might explain local variance in the incidence of oral cancers within Changhua and
      their prevalence in the county as a whole. The paper contains results from a
      retrospective review of medical records for patients diagnosed with oral cancer
      in Changhua County who were treated at the Changhua Christian Hospital (CCH)
      between 1994 and 2005. The Wilcoxon signed rank test, ANOVA, t-test, Kaplan-Meier
      curve and log-rank tests were carried out to examine the association between
      patients' places of residence, their ages at diagnosis, and their overall
      prognoses. A total of 1363 oral cancer cases were diagnosed in the study period.
      These consisted of 1272 males and 91 females. A steady increase in the number of
      patients diagnosed with oral cancer annually was noted. The tongue and buccal
      mucosa were the two most frequently affected sites constituting 56% of cases,
      while squamous cell carcinoma was diagnosed in nearly 80% of the study
      population. The mean ages at diagnosis were 53.1 and 52.8 years for patients
      living in the northern and central areas of Changhua, and 55.1 years for those
      living in the south. Patients living in the northern and central areas of
      Changhua had poorer long-term prognoses as indicated by Kaplan-Meier survival
      curves and the log-rank test, and it appears that differences in the level, type
      and distribution of industry in these areas distinguish these patients from those
      living in the south of the county. In particular, the density of electroplating
      factories in northern and central Changhua is significantly higher than in the
      south. Patients living in northern and central areas of Changhua have their oral
      cancers diagnosed at a younger age and have poorer long-term prognoses than those
      living in the south of the county in spite of their being treated at the same
      hospital. We conclude that factors explaining local differences in the prognosis
      of oral cancer patients in this part of Taiwan require further investigation, as
      does Changhua's high overall incidence for these cancers.

PMID- 18620899
TI  - In vitro photodynamic therapy on human oral keratinocytes using chloroaluminum
      phthalocyanine.
AB  - In this study, oral carcinoma cells were used to evaluate chloroaluminum
      phthalocyanine encapsulated in liposomes as the photosensitizer agent in support
      of photodynamic therapy (PDT). The genotoxicity and cytotoxicity behavior of the
      encapsulated photosensitizer in both dark and under irradiation using the 670-nm
      laser were investigated with the classical trypan blue cell viability test, the
      acridine orange/ethidium bromide staining organelles test, micronucleus formation
      frequency, DNA fragmentation, and cell morphology. The cell morphology
      investigation was carried out using light and electronic microscopes. Our
      findings after PDT include reduction in cell viability (95%) associated with
      morphologic alterations. The neoplastic cell destruction was predominantly
      started by a necrotic process, according to the assay with acridine orange and
      ethidium bromide, and this was confirmed by electronic microscopy analysis.
      Neither the PDT agent nor laser irradiation alone showed cytotoxicity,
      genotoxicity, or even morphologic alterations. Our results reinforce the
      efficiency of light-irradiated chloroaluminum-phthalocyanine in inducing a
      positive effect of PDT.

PMID- 18620900
TI  - Epiregulin promotes migration and invasion of salivary adenoid cystic carcinoma
      cell line SACC-83 through activation of ERK and Akt.
AB  - Hematogenous metastasis is one of the most important factors determining the
      outcome of the patients with salivary adenoid cystic carcinoma (SACC). In the
      present study, we examined expression profile of genes in SACC cell lines to look
      for molecules responsible for its unique metastatic trait. A transcriptomic
      microarray analysis between the lower lung-metastatic rate cell line SACC-83 and
      the higher lung-metastatic rate cell line SACC-LM were performed, and eight
      genes, showed by microarray to be highly expressed in SACC-LM, were picked for
      validation by quantitative real-time PCR. Among the genes, the expression of
      epiregulin, a novel member of epidermal growth factor family, was 350-folds
      higher in SACC-LM than in SACC-83. Accordingly, we examined the effects of
      epiregulin on migration and invasion in SACC-83 as well as its targeted
      downstream molecules, and found that epiregulin could promote in vitro migration
      and invasion in SACC-83. Furthermore, epiregulin not only induced activation of
      both ERK1/2 and Akt, but also expression of COX-2. In addition, all these effects
      could be partially blocked by U0126, a specific inhibitor of mitogen-activated
      protein kinase kinase (MEK or MAPKK), or LY294002, a specific inhibitor of
      phosphatidylinositol 3-kinase (PI3K). Conclusively, the results suggest that
      epiregulin may play an important role in lung metastasis of SACC.

PMID- 18620901
TI  - Is there a role for the Fas-/Fas-Ligand pathway in chemoresistance of human
      squamous cell carcinomas of the head and neck (SCCHN)?
AB  - The aim of the present investigation was to determine the expression of the Fas
      receptor/ligand system in established cell lines of squamous cell carcinomas of
      the head and neck (SCCHN), and to study it's functional impact on chemotherapy
      induced apoptosis in these SCCHN cell lines. We observed constitutive expression
      of Fas and FasL in 13 SCCHN cell lines by RT-PCR, Southern-blotting and
      immunocytochemistry, respectively. Administration of the agonistic Fas-antibody
      CH-11 led to a significant reduction of viable cells in the colorimetric MTT
      assay in 5 out of 13 (38%) cell lines tested and preincubation with Interferon
      gamma (IFN-gamma) rendered 3 (23%) primarily resistant cell lines sensitive.
      Cisplatin (cDDP) and bleomycin (BLM) caused dose-dependent cytotoxicity in all
      cell lines as determined by the 50% inhibitory concentration (IC(50)) and
      induction of apoptosis. Furthermore, both antineoplastic agents led to an
      enhanced surface expression of Fas and FasL in all cell lines, and this effect
      was independent of the respective p53-status. This upregulation of Fas/FasL
      surface expression increased preexisting Fas-sensitivity only, but failed to make
      primarily resistant cell lines undergo Fas-mediated growth reduction or
      apoptosis. Vice versa, blockade of Fas-receptor-ligand-interactions by monoclonal
      antibodies directed against FasL was able to attenuate the cytotoxic effect of
      cDDP and BLM in 2 out of 5 (40%) cell lines tested only. In conclusion, in
      contrast to many other solid tumors, the Fas/FasL-system does not seem to play an
      exclusive role in anticancer drug mediated apoptosis in SCCHN.

PMID- 18620902
TI  - The prognostic value of hypoxia markers in T2-staged oral tongue cancer.
AB  - Tumor hypoxia is associated with poorer outcome in patients with head and neck
      carcinomas, but little is known about hypoxia biomarkers in oral tongue cancer.
      We evaluated whether hypoxia biomarkers and clinicopathologic variables were
      prognostic predictors in patients with T2-staged squamous cell carcinoma (SCC) of
      the oral tongue. Tissue microarrays were constructed from formalin-fixed tumor
      blocks of 43 patients with T2-staged tongue SCCs treated by surgical resection
      and neck dissection. Tissue samples were stained with monoclonal antibodies to
      hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase (CA)-9,
      glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR). Locoregional
      control and survival rates were calculated by the Kaplan-Meier method, and
      prognostic factors were calculated from uni- and multivariate analyses. Tumor
      thickness was correlated with expression of CA-9 and GLUT-1 and nodal
      classification was correlated with GLUT-1 expression. The nodal metastasis rate
      was 51%, and the 5-year locoregional control and disease-specific survival (DSS)
      rates were 59% and 69%, respectively. Univariate analysis showed that HIF-1alpha
      and EPOR expression were significantly related to DSS. Multivariate analysis
      showed that EPOR expression was an independent predictor of DSS (P=0.030). EPOR
      expression may be an independent predictor for DSS in patients with T2-staged SCC
      of the oral tongue.

PMID- 18620903
TI  - The design and development of a physician-oriented PACS for the enhancement of e
      hospital facilities.
AB  - Recent advancements in modern medical diagnoses have required a huge increase of
      the use of equipment such as CT and ultrasound machines. Correspondingly, the
      storage and dissemination of these medical images have become an important issue
      to medical professionals. Unfortunately, management of these images has
      traditionally been slow and cumbersome. With the prevalence of the personal
      computer, however, along with increased network bandwidth, it is now possible to
      handle this information electronically as well as wirelessly. The Picture
      Archiving and Communication System (PACS) is at the forefront of this revolution.
      Yet, commercially available PACS software is generally prohibitively expensive
      for hospitals with limited financial resources. A dilemma among many hospitals is
      deciding how to acquire and implement the proper PACS system without unduly
      affecting the budget. In this paper, a full function, efficient, and economical
      PACS system is presented as a viable, non-compromising option for many small and
      medium-sized hospitals. This system, designed and developed mainly by the
      physicians and technicians of Puli Christian Hospital (PCH), with the assistance
      from academia, allows for customization to fit the needs of individual hospitals.
      This system can be used as the foundation of a hospital's health information
      infrastructure and to enhance e-hospital service.

PMID- 18620904
TI  - Origin of frontal lobe spikes in the early onset benign occipital lobe epilepsy
      (Panayiotopoulos syndrome).
AB  - OBJECTIVE: Early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome
      [PS]) is a common and easily recognizable epilepsy. Interictal EEG spike activity
      is often multifocal but most frequently localized in the occipital lobes. The
      origin and clinical significance of the extra-occipital spikes remain poorly
      understood. METHODS: Three patients with the PS and interictal EEG spikes with
      frontal lobe topography were studied using high-resolution EEG. Independent
      component analysis (ICA) was used to decompose the spikes in components with
      distinct temporal dynamics. The components were mapped in the scalp with a spline
      laplacian algorithm. RESULTS: The change in scalp potential topography from spike
      onset to peak, suggests the contribution of several intracranial generators, with
      different kinetics of activation and significant overlap. ICA was able to
      separate the major contributors to frontal spikes and consistently revealed an
      early activating group of components over the occipital areas in all the
      patients. The local origin of these early potentials was established by the
      spline-laplacian montage. CONCLUSIONS: Frontal spikes in PS are consistently
      associated with early and unilateral occipital lobe activation, suggesting a
      postero-anterior spike propagation. SIGNIFICANCE: Frontal spikes in the PS
      represent a secondary activation triggered by occipital interictal discharges and
      do not represent an independent focus.

PMID- 18620905
TI  - Somatotopic representation of the tongue in human secondary somatosensory cortex.
AB  - OBJECTIVE: To clarify the somatotopic representation of the tongue secondary
      somatosensory cortex (SII) in humans. METHODS: Somatosensory evoked magnetic
      fields (SEFs) were recorded from nine subjects after stimulating four body sites,
      left antero (LA) and postero (LP) lateral margins of the tongue, left median
      nerve at the wrist (Hand), and left tibial nerve at the ankle (Foot). RESULTS:
      Clear neural activities were recorded from the bilateral SII in both hemispheres
      after the four sites were stimulated. The tongue SII for LA and LP was located
      close to the hand SII and significantly more anterior than the Foot SII. There
      was no significant difference in the location of dipoles between the LA and LP
      areas of the tongue SII. The mean peak latencies of the tongue SII for LA and LP
      were significantly shorter in the hemisphere contralateral to the stimulation
      than the ipsilateral hemisphere. CONCLUSIONS: The tongue areas are considered to
      occupy a small region in SII with insufficient spatial separation to
      differentiate anterior from posterior areas even using magnetoencephalography
      which has a higher spatial resolution than electroencephalography (EEG).
      SIGNIFICANCE: This is the first systematical study to clarify the activated
      regions in SII following stimulation of the tongue.

PMID- 18620906
TI  - Neural generators of brain potentials before rapid eye movements during human REM
      sleep: a study using sLORETA.
AB  - OBJECTIVE: Brain activity preceding rapid eye movements (REM) during human REM
      sleep has remained poorly understood. Slow negative brain potential (pre-REM
      negativity) appears before REMs. Current sources of this potential were
      investigated to identify brain activity immediately preceding REMs. METHODS: In
      this study, 22 young healthy volunteers (20-25 years old) participated.
      Polysomnograms were recorded during normal nocturnal sleep. Brain potentials
      between 200ms before and 50ms after the onset of REMs and pseudo-triggers (3000ms
      before the onset of REMs) were averaged. Standardized low-resolution brain
      electromagnetic tomography (sLORETA) was used to estimate current sources of pre
      REM negativity. RESULTS: Pre-REM negativity appeared with the maximal amplitude
      at right prefrontal sites immediately before REMs. However, this negativity did
      not appear before pseudo-triggers. Current sources of the pre-REM negativity were
      estimated in the ventromedial prefrontal cortex, uncus, insula, anterior
      cingulated cortex, basal forebrain, parahippocampal gyrus, premotor cortex and
      frontal eye field. CONCLUSIONS: The pre-REM negativity reflects brain activity
      coupled with the occurrence of REMs. Results of this study suggest that emotion,
      memory, and motor-related brain activity might occur before REMs. SIGNIFICANCE:
      Pre-REM negativity is expected to be a psychophysiological index for elucidating
      functions of REM sleep.

PMID- 18620907
TI  - Effects of allocation of visuo-spatial attention to visual stimuli triggering
      unilateral arm abduction on anticipatory postural control.
AB  - OBJECTIVE: We investigated the effects of allocation of visuo-spatial attention
      to visual stimuli triggering arm movement on anticipatory postural control.
      METHODS: Fourteen healthy right-handed subjects participated in the study. Visual
      stimuli were randomly presented to the left or right visual field on a screen. An
      attention-directing cue or a non-directional cue was presented at 1000ms before
      visual stimulus onset. Subjects focused or divided visuo-spatial attention
      (focused- and divided-attention conditions, respectively) based on types of cues,
      and abducted the left or right arm rapidly in response to target stimuli (with
      30% probability of visual stimuli) according to the side of presentation. Peak-to
      peak amplitude of P1 and N1 components of event-related potentials (P1-N1
      amplitude) elicited by visual stimuli and activation timing of postural muscles
      with respect to the middle deltoid were measured. RESULTS: Compared with divided
      attention condition, in focused-attention condition P1-N1 amplitude at occipital
      electrodes was enhanced and activation of the left hip abductors during right arm
      abduction was hastened. A significant correlation was observed between the
      attention-related changes in these two measurements. CONCLUSIONS: Anticipatory
      postural control during right arm abduction was influenced by attention-related
      modulation of sensory-perceptual processing. SIGNIFICANCE: These findings are
      important for understanding of the effects of visuo-spatial attention on
      anticipatory postural control.

PMID- 18620908
TI  - Carpal tunnel syndrome: ultrasound, neurophysiology, clinical and patient
      oriented assessment.
AB  - OBJECTIVE: The aim of this study is twofold. First, to assess the relationships
      between the cross-sectional area (CSA) of the median nerve (MN) calculated at
      ultrasound (US) and: (1) patient's perception of his/her symptoms and hand
      function; (2) clinical severity of CTS; (3) neurophysiological classification;
      (4) hand distribution of symptoms. Second, to assess the sensitivity of
      ultrasonography (US) and neurophysiology in the diagnosis of CTS using clinical
      measures as gold standard. METHODS: We performed a prospective study by using
      multidimensional assessment: clinical (Historic and Objective scale, Hi-Ob),
      neurophysiological, patient-oriented measures (Boston Carpal Tunnel
      Questionnaire, BCTQ) and high-resolution US. The dominant hands of 54 consecutive
      patients who were referred to our neurophysiologic laboratory with clinical signs
      of CTS (43 females, mean age 53.3, range 30-80, SD: 13.1) were examined. RESULTS:
      A statistically significant correlation was found between the CSA of the MN at
      wrist and (1) hand function (according to BCTQ, r=0.35, p=0.01), (2) clinical
      scale (Hi-Ob scale, r=0.51, p<0.00007), (3) neurophysiologic classification
      (r=0.80, p<0.0000001), and (4) hand distribution of symptoms (p=0.017).
      Neurophysiology showed higher sensitivity than US but in one of 3 cases with
      normal neurophysiological results, US showed data suggestive of CTS. CONCLUSIONS:
      A positive correlation exists between US findings and all the conventional
      measures of CTS severity. The sensitivity of the combination of US and
      neurophysiology is higher than the sensitivity of neurophysiology or US alone. US
      is a useful complementary tool for CTS assessment. SIGNIFICANCE: Information on
      the contribution of US in CTS and the interpretation of severity measurements in
      CTS.

PMID- 18620910
TI  - A simple and reliable method for determining plasma concentration of
      dehydroxymethylepoxyquinomicin by high performance liquid chromatography with
      mass spectrometry.
AB  - We have developed a simple and reliable method for determining plasma
      concentration of dehydroxymethylepoxyquinomicin (DHMEQ), a new low molecular
      weight NF-kappaB inhibitor, using high performance liquid chromatography with
      mass spectrometry (LC-MS). An experiment of mass spectrometry with electrospray
      ionization in the negative ionization mode was performed to detect ion
      transitions at m/z 260.05 [M-H](-) for DHMEQ and 240.29 for mefenamic acid as an
      internal standard. The samples were purified using liquid-liquid extraction with
      ethyl acetate. The method yielded a standard curve which was linear for the
      concentration range of 0.1-125 ng/mL when 0.05 mL plasma was used. The
      correlation coefficients of all standard curves were greater than or equal to
      0.999. The limit of detection was 50 pg/mL (signal/noise >3). Daily fluctuation
      of plasma standard curve was small. The intra- and inter-assay precision ranged
      from 2.84 to 4.76% (n=6) and 2.91 to 7.03% (n=6), respectively. The LC-MS
      technique described provides a simple and reliable liquid chromatographic method
      for the determination of DHMEQ level and for use in studies involving
      pharmacokinetics.

PMID- 18620909
TI  - Memory B cells in common variable immunodeficiency: clinical associations and sex
      differences.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized
      by impaired antibody responses, recurrent infections, inflammatory, autoimmune
      and malignancy-related conditions. We evaluated the relationship between memory B
      cell phenotype, sex, age at diagnosis, immunologic and clinical conditions in 105
      CVID subjects from one medical center. Reduced numbers of switched memory B cells
      (cutoff <or=0.55% of B cells) were an independent risk factor of granulomas,
      autoimmune diseases and splenomegaly (p<0.001). Not previously noted, CVID
      females had significantly more switched memory cells (p=0.007) than males.
      Splenectomized subjects did not have fewer IgM memory B cells and these numbers
      were not related to the development of lung disease, as previously proposed.
      Lower baseline serum IgG was an independent predictor of pneumonia (p=0.007) and
      severe infections (p=0.001). We conclude that outcomes in CVID depend on an
      interplay of factors including sex, numbers of switched memory B cells, and
      baseline serum IgG and IgA levels.

PMID- 18620911
TI  - Accurate identification and quantification of 11-nor-delta(9)
      tetrahydrocannabinol-9-carboxylic acid in urine drug testing: evaluation of a
      direct high efficiency liquid chromatographic-mass spectrometric method.
AB  - A direct liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for
      measurement of urinary Delta(9)-tetrahydrocannabinol carboxylic acid (THCA) was
      developed. The method involved dilution of the urine sample with water containing
      (2)H(9)-deuterated analogue as internal standard, hydrolysis with ammonia,
      reversed phase chromatography using a Waters ultra-performance liquid
      chromatography (UPLC) equipment with gradient elution, negative electrospray
      ionization, and monitoring of two product ions in selected reaction monitoring
      mode. The measuring range was 2-1000 ng/mL for THCA, and the intra- and inter
      assay imprecision, expressed as the coefficient of variation, was below 5%.
      Influence from urine matrix on ionization efficiency was noted in infusion
      experiments, but was compensated for by the internal standard. Comparison with
      established gas chromatography-mass spectrometry and liquid chromatography-mass
      spectrometry methods in authentic patient samples demonstrated accuracy in both
      qualitative and quantitative results. A small difference in mean ratios (~15%)
      may be explained by the use of different hydrolysis procedures between methods.
      In conclusion, the high efficiency LC-MS/MS method was capable of accurately
      identify and quantify THCA in urine with a capacity of 14 samples per hour.

PMID- 18620912
TI  - Phenotype differentiation of three E. coli strains by GC-FID and GC-MS based
      metabolomics.
AB  - Two mutants of E. coli with deletion of sdhAB and ackA-pta genes respectively and
      their wild-type strains were subjected to gas chromatography-flame-ionization
      detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) metabolomics
      analysis. Intracellular metabolites of the three strains were profiled by GC-FID
      firstly. Methodological evaluation of the employed platform indicated that the
      limit of detection ranges were from 0.2 to 12.5 ng for some representative
      metabolites and the corresponding recoveries were varied from 68.7 to 122.7%.
      Secondly, multivariable data analysis was applied to the acquired data sets. As
      expected, the three phenotypes could be easily differentiated, and the perturbed
      metabolite pools in the genetically modified strains were screened. Lastly, the
      metabolites playing key roles in the differentiation were further identified by
      GC-MS. It was confirmed that succinic acid and aspartic acid were similarly
      affected in the modified strains. But proline content was altered contrarily.
      Additionally, deletion of sdhAB gene also affected the growth property of
      relevant mutant greatly. The potential mechanism was postulated accordingly.

PMID- 18620913
TI  - Endoclipping for gastric perforation secondary to second session of EMRC in
      locally residual early gastric cancer: a case report.
AB  - A 72-year-old woman underwent gastric endoscopic mucosal resection with a cap
      fitted endoscope for an adenocarcinoma in situ. She was scheduled for endoscopic
      follow-up at 1 and 3 months after the procedure. By the third month of follow up,
      biopsies of a slightly depressed scar area showed an high grade epithelial
      dysplasia. For this reason a second endoscopic resection (ER) was performed using
      the oblique soft cap. A perforation in the site of endoscopic resection was
      immediately observed. The complication was treated successfully by the
      application of seven clips.

PMID- 18620914
TI  - Endoscopic endonasal reduction surgery for diplopia caused by orbital roof
      fractures.
AB  - BACKGROUND: Orbital roof fractures (ORF) frequently occur together with frontal
      bone fractures, and can cause diplopia as a sequela. However, ORF have never been
      treated using endoscopic endonasal reduction surgery. CASE: A 22-year-old woman
      was injured in a traffic accident and diagnosed with right ORF along with frontal
      bone fractures. She was referred to us for diplopia 2 weeks after the initial
      trauma. No facial deformation was seen. Endoscopic endonasal reduction surgery
      was performed under general anaesthesia. Ethmoidectomy was performed and,
      subsequently, the anterior superior portion of the medial orbital bone was
      removed. During the procedure, an ophthalmologist performed eye traction tests
      until definitive ocular motility improvement was observed. RESULTS AND
      CONCLUSION: Postoperatively, diplopia disappeared and no enophthalmos was seen.
      From both a functional and an aesthetic point of view, the endoscopic endonasal
      reduction surgery resulted in a satisfactory outcome without having to use any
      extranasal approaches in this case.

PMID- 18620915
TI  - Mass spectrometry of the fifth nucleoside: a review of the identification of
      pseudouridine in nucleic acids.
AB  - Pseudouridine, the so-called fifth nucleoside due to its ubiquitous presence in
      ribonucleic acids (RNAs), remains among the most challenging modified nucleosides
      to characterize. As an isomer of the major nucleoside uridine, pseudouridine
      cannot be detected by standard reverse-transcriptase-based DNA sequencing or
      RNase mapping approaches. Thus, over the past 15 years, investigators have
      focused on the unique structural properties of pseudouridine to develop selective
      derivatization or fragmentation strategies for its determination. While the N
      cyclohexyl-N'-beta-(4-methylmorpholinium)ethylcarbodiimide p-tosylate (CMCT)
      reverse transcriptase assay remains both a popular and powerful approach to
      screen for pseudouridine in larger RNAs, mass-spectrometry-based approaches are
      poised to play an increasingly important role in either confirming the findings
      of the CMCT-reverse transcriptase assay or in characterizing pseudouridine
      sequence placement and abundance in smaller RNAs. This review includes a brief
      discussion of pseudouridine including a summary of its biosynthesis and known
      importance within various RNAs. The review then focuses on chemical
      derivatization approaches that can be used to selectively modify pseudouridine to
      improve its detection, and the development of mass-spectrometry-based assays for
      the identification and sequencing of pseudouridine in various RNAs.

PMID- 18620917
TI  - Bromine determination in polymers by inductively coupled plasma-mass spectrometry
      and its potential for fast first screening of brominated flame retardants in
      polymers and paintings.
AB  - The impact of brominated flame retardants (BFRs) on the environment and their
      potential risk in animal and human health is a present concern. Therefore,
      existing legislation in the European Union demands that polymers with BFRs are
      identified and eliminated from the recycling process due to their potential
      health hazard. In this work, a flow-injection (FI) system coupled to inductively
      coupled plasma-mass spectrometry (ICP-MS) was optimized for the detection of
      traces of bromine in polymers, plastic paints and enamels containing BFRs. Sample
      preparation requires a microwave-assisted digestion in order to transfer bromine
      in polymeric samples to solution. After appropriate optimization of the digestion
      procedure and the ICP-MS detection, a detection limit (DL) of 4.2 mg kg(-1) was
      obtained for synthesized polyurethane standards containing known concentrations
      of bromine. The precision of the proposed method, evaluated as the R.S.D. of
      signals obtained for three replicates of polymeric standard BFRs at the normative
      EU level, was as low as 3.6%. This simple developed methodology was characterized
      for the screening of bromine in polymeric matrices. The proposed system provides
      rapid binary yes/no overall responses, being appropriate for the screening of
      bromine above a pre-set concentration threshold. The unreliability region (UR),
      given by the probability of false positives and false negatives (set at 5% in
      both cases), was in the range between 442 and 678 mg kg(-1) of bromine (at a cut
      off level of 0.1% in BFRs by weight of homogeneous material fixed by the EU
      normative). Finally, the applicability of the proposed screening system was
      tested for the reliable control of bromine in different commercial samples
      including flame-retardant paints and enamels.

PMID- 18620916
TI  - High-accuracy determination of iron in seawater by isotope dilution multiple
      collector inductively coupled plasma mass spectrometry (ID-MC-ICP-MS) using
      nitrilotriacetic acid chelating resin for pre-concentration and matrix
      separation.
AB  - In the present paper we describe a robust and simple method to measure dissolved
      iron (DFe) concentrations in seawater down to <0.1 nmol L(-1) level, by isotope
      dilution multiple collector inductively coupled plasma mass spectrometry (ID-MC
      ICP-MS) using a (54)Fe spike and measuring the (57)Fe/(54)Fe ratio. The method
      provides for a pre-concentration step (100:1) by micro-columns filled with the
      resin NTA Superflow of 50 mL seawater samples acidified to pH 1.9. NTA Superflow
      is demonstrated to quantitatively extract Fe from acidified seawater samples at
      this pH. Blanks are kept low (grand mean 0.045+/-0.020 nmol L(-1), n=21, 3 x S.D.
      limit of detection per session 0.020-0.069 nmol L(-1) range), as no buffer is
      required to adjust the sample pH for optimal extraction, and no other reagents
      are needed than ultrapure nitric acid, 12 mM H(2)O(2), and acidified (pH 1.9)
      ultra-high purity (UHP) water. We measured SAFe (sampling and analysis of Fe)
      reference seawater samples Surface-1 (0.097+/-0.043 nmol L(-1)) and Deep-2
      (0.91+/-0.17 nmol L(-1)) and obtained results that were in excellent agreement
      with their DFe consensus values: 0.118+/-0.028 nmol L(-1) (n=7) for Surface-1 and
      0.932+/-0.059 nmol L(-1) (n=9) for Deep-2. We also present a vertical DFe profile
      from the western Weddell Sea collected during the Ice Station Polarstern (ISPOL)
      ice drift experiment (ANT XXII-2, RV Polarstern) in November 2004-January 2005.
      The profile shows near-surface DFe concentrations of approximately 0.6 nmol L(-1)
      and bottom water enrichment up to 23 nmol L(-1) DFe.

PMID- 18620918
TI  - Quality control and original discrimination of Ganoderma lucidum based on high
      performance liquid chromatographic fingerprints and combined chemometrics
      methods.
AB  - In this paper, the feasibility and advantages of employing high-performance
      liquid chromatographic (HPLC) fingerprints combined with chemometrics methods for
      quality control of the cultured fruiting bodies of Ganoderma lucidum were
      investigated and demonstrated for the first time. In order to compare the HPLC
      fingerprints chromatograms between G. lucidum from different origins, the
      similarities of all the 60 samples and relative peak areas of 19 characteristic
      compounds were firstly calculated respectively. Then different pattern
      recognition procedures, including hierarchical cluster analysis (HCA), principal
      component analysis (PCA), partial least squares-discrimination analysis (PLS-DA)
      and soft independent modeling of class analogy (SIMCA) were applied to classify
      the G. lucidum samples according to their cultivated origins. Consistent results
      were obtained to show that G. lucidum samples could be successfully grouped in
      accordance with the province of origin. Furthermore, four marker constituents
      were screened out to be the most discriminant variables, which could be applied
      to accurate discrimination and quality control of G. lucidum by quantitative
      analysis. Finally, the chemical properties of those samples were also
      investigated to find out the differences of quality between them. Ranked in
      decreasing order, the quality of the G. lucidum can be arranged as
      Jinzhai/Huangshan, Shandong followed by Zhejiang samples. Our results revealed
      that the developed method has potential perspective for the original
      discrimination and quality control of G. lucidum.

PMID- 18620920
TI  - A novel separation/preconcentration system based on solidification of floating
      organic drop microextraction for determination of lead by graphite furnace atomic
      absorption spectrometry.
AB  - Solidified floating organic drop microextraction (SFODME) was successfully used
      as a sample preparation method for graphite furnace atomic absorption
      spectrometry (GFAAS). 20 microL of 1-undecanol containing dithizone as the
      chelating agent (2x10(-4) mol L(-1)) was transferred to the water samples
      containing lead ions, and the solution was stirred for the prescribed time. The
      sample vial was cooled in an ice bath for 5 min. The solidified extract was
      transferred into a conical vial where it melted immediately, and then 10 microL
      of it was analyzed by GFAAS. Factors that influence the extraction and complex
      formation, such as pH, concentration of dithizone, extraction time, sample
      volume, and ionic strength were optimized. Under the optimized conditions, a good
      relative standard deviation of +/-5.4% at 10 ng L(-1) and detection limit of 0.9
      ng L(-1) were obtained. The procedure was applied to tap water, well water, river
      water and sea water, and accuracy was assessed through the analysis of certified
      reference water or recovery experiments.

PMID- 18620919
TI  - Assays for serum cholinesterase activity by capillary electrophoresis and an
      amperometric flow injection choline biosensor.
AB  - A capillary electrophoresis method and a durable choline biosensor were developed
      for measuring serum cholinesterase (EC 3.1.1.8) activity, a useful clinical index
      for liver function. The former is based on separation of benzoate and
      benzoylcholine (the artificial substrate of cholinesterase) in an uncoated fused
      silica capillary. The migration time of benzoylcholine and benzoate was 1.3 min
      and 5.5 min, respectively. By the peak areas of A(233) signals, the linear
      dynamic ranges for both analytes were 0.01-50.0 mM, and the relative standard
      deviations of 1.0 mM benzoylcholine and benzoate were less than 4% and 6%,
      respectively. The FIA-choline sensor was constructed with the working electrode
      of the flow cell covered with a natural chitinous membrane purified from
      Taiwanese soldier crab, Mictyris brevidactylus. The biomembrane served as the
      supporting material for enzyme immobilization (choline oxidase, EC 1.1.3.17), and
      also prevented protein adsorption on the electrode surface. The calibration curve
      was linear between 0.05 and 5.0 mM (r=0.999). The relative standard deviations
      for 1.0 mM choline (n=7) were less than 3%, and the activity of the bioactive
      membrane lasted for about 2 months. The analytical results of both methods
      correlated well (r=0.940).

PMID- 18620921
TI  - Analysis of steroids in yeast-mediated cell culture by on-line solid-phase
      extraction coupled high-performance liquid chromatography electrospray
      ionization/mass spectrometry and novel continuous postcolumn infusion of internal
      standard technique.
AB  - The reduction of 17-ketosteroid estrone or androstenedione to corresponding
      17alpha- and 17beta-estradiol or testosterone and epitestosterone has been
      performed with Saccharomyces cerevisiae. In the analysis of the cell culture, the
      solid-phase extraction (SPE) method was on-line coupled to high-performance
      liquid chromatography electrospray-ionization/mass spectrometry (HPLC-ESI/MS) for
      sample pretreatment to eliminate the complicated matrix interference and
      preconcentrate of the analytes before chromatographic separation. A novel
      quantification method with the continuous postcolumn infusion of internal
      standard was developed for the determination of substrate and products. This
      novel quantitative method can stabilize and enhance the ionization of all
      analytes during analysis. The HPLC-ESI/MS analysis of estrone, 17alpha-, and
      17beta-estradiol was operated with a negative ion mode and the analysis of
      androstenedione, testosterone, and epitestosterone was operated with a positive
      ion mode. The optimal concentration of the internal standard progesterone with
      the continuous postcolumn infusion technique was 3 microg mL(-1) for estrogen
      analysis and 1 ng mL(-1) for androgen analysis and both were at a constant
      infusion rate of 0.5 microL min(-1). All of the linear correlation coefficients
      of the standard calibration curves were over 0.99 and had a linear range from 0
      to 50 ng mL(-1). The limit of detections (LODs) and the limit of quantitations
      (LOQs) for steroids analyzed were from 0.12 to 0.36 ng mL(-1) and from 0.4 to 1.2
      ng mL(-1), respectively. The analysis accuracies and precisions were better than
      94% and lower than 8.8% R.S.D., respectively. The developed method for the
      analysis of steroids in the cell culture was successful.

PMID- 18620922
TI  - Assessment of hand-held Raman instrumentation for in situ screening for
      potentially counterfeit artesunate antimalarial tablets by FT-Raman spectroscopy
      and direct ionization mass spectrometry.
AB  - Pharmaceutical counterfeiting has become a significant public health problem
      worldwide and new, rapid, user-friendly, reliable and inexpensive methods for
      drug quality screening are needed. This work illustrates the chemical
      characterization of genuine and fake artesunate antimalarial tablets by portable
      Raman spectroscopy and validation by FT-Raman spectroscopy and ambient mass
      spectrometry. The applicability of a compact and robust portable Raman
      spectrometer (TruScan) for the in situ chemical identification of counterfeit
      tablets is reported.

PMID- 18620923
TI  - Analysis of a coloured Dutch map from the eighteenth century: the need for a
      multi-analytical spectroscopic approach using portable instrumentation.
AB  - A Dutch map from the eighteenth century was multi-analytically analysed making
      use of energy dispersive X-ray fluorescence (EDXRF), Fourier transform infrared
      spectroscopy (FTIR), nuclear magnetic resonance (NMR), Raman and scanning
      electron microscopy coupled to energy dispersive spectrometry (SEM-EDS). The
      cellulosic support was characterised and its state of conservation was evaluated.
      Besides, paramagnetic impurities were detected together with copper metallic
      chips. The colours present in some areas of the map were also analysed.
      Vermilion, carbon black and organic pigments were found. Surprisingly, in the
      green areas, the rare presence of the mineral moolooite (copper oxalate) was
      detected. A possible biological attack is discussed in order to explain the
      presence of such compound. Almost all of the techniques used in the analysis were
      portable, non-destructive and non-invasive, which is very desirable when
      analysing objects belonging to Cultural Heritage. The need for a multi-analytical
      approach using portable instrumentation is also discussed.

PMID- 18620924
TI  - Development of an optical surface plasmon resonance biosensor assay for
      (fluoro)quinolones in egg, fish, and poultry meat.
AB  - The aim of this study was to develop an optical biosensor inhibition immunoassay,
      based on the surface plasmon resonance (SPR) principle, for use as a screening
      test for 13 (fluoro)quinolones, including flumequine, used as veterinary drugs in
      food-producing animals. For this, we immobilised various quinolone derivatives on
      the sensor chip and tested binding of a range of different antibodies (polyclonal
      and one engineered antibody) in the presence and absence of free
      (fluoro)quinolones. The main challenge was to detect flumequine in an assay
      giving good results for the other compounds. One antigen-antibody combination
      proved satisfactory: polyclonal antibodies raised against a dual immunogen and,
      on the sensor chip, a fluoroquinolone derivative. It was the first time that this
      concept of the bi-active antibody was described in the literature. The assay,
      optimised for detection in three matrices (poultry muscle, fish, and egg), was
      tested on incurred samples prepared by liquid extraction followed by two washing
      steps. This rapid, simple method proved adequate for detecting at least 13
      (fluoro)quinolones at concentrations below established maximum residue levels
      (MRLs). The reference molecule norfloxacin could be detected in the range of 0.1
      10 microg kg(-1) in extracts of egg and poultry meat and in the range of 0.1-100
      microg kg(-1) in extracts of fish. The determined midpoints of these calibration
      curves were about 1, 1.5 and 3 microg kg(-1) in poultry meat, egg and fish,
      respectively.

PMID- 18620925
TI  - Approach for non-destructive pigment analysis in model liquids and carrots by
      means of time-of-flight and multi-wavelength remittance readings.
AB  - Non-destructive spectroscopy in the visible and near infrared wavelength range
      has been introduced for analyzing absorbing compounds in fruit and vegetables. A
      drawback of the method appears due to the measuring principle, where photons
      detected in the diffusive tissue are influenced by the sample absorption but also
      scattering properties leading to variation in the photon pathlength. In the
      present work, distribution of time-of-flight reading was used to calculate the
      effective pathlength between source and detector. Using this information in
      addition to the spectral intensities obtained with common continuous wave
      spectroscopy, Lambert-Beer law was applied for analyzing absolute pigment
      contents. The method was tested for liquid phantoms mimicking the optical
      properties of fresh fruit and vegetables. Lambert-Beer law using a constant
      pathlength as well as combined application of the intensity at a specific
      wavelength and the effective pathlength resulted in low calibration errors with
      r(2)>0.98. Applying the two calibrations on phantoms mimicking changes in the
      scattering properties resulted in validation results of r(2)=0.47 and 0.64,
      respectively. Improved results by using the effective pathlength were confirmed
      on real-world samples. The carrot carotenoids analysis resulted in validation
      results of r(2)=0.66 and 0.74, respectively, while the measuring uncertainty was
      reduced from 18.10 to 9.62%. Multivariate calibrations using the entire carrot
      spectra and data pre-processing aiming the reduction of scattering effects
      resulted in slightly lower measuring uncertainty by comparison. In the sensor
      fusion approach proposed, however, no expensive spectrophotometer is required and
      the phenomenon of varying optical properties of the sample is characterized.

PMID- 18620926
TI  - An electropolymerized Nile Blue sensing film-based nitrite sensor and application
      in food analysis.
AB  - This paper reports a poly-Nile Blue (PNB) sensing film based electrochemical
      sensor and the application in food analysis as a possible alternative for
      electrochemical detection of nitrite. The PNB-modified electrode in the sensor
      was prepared by in situ electropolymerization of Nile Blue at a prepolarized
      glassy carbon (GC) electrode and then characterized by cyclic voltammetry (CV)
      and pulse voltammetry in phosphate buffer (pH 7.1). Several key operational
      parameters affecting the electrochemical response of PNB sensing film were
      examined and optimized, such as polarization time, PNB film thickness and
      electrolyte pH values. As the electroactive PNB sensing film provides plenty of
      active sites for anodic oxidation of nitrite, the nitrite sensor exhibited high
      performance including high sensitivity, low detection limit, simple operation and
      good stability at the optimized conditions. The nitrite sensor revealed good
      linear behavior in the concentration range from 5.0x10(-7) mol L(-1) to 1.0x10(
      4) mol L(-1) for the quantitative analysis of nitrite anion with a limit of
      detection of 1.0x10(-7) mol L(-1). Finally, the application in food analysis
      using sausage as testing samples was investigated and the results were consistent
      with those obtained by standard spectrophotometric method.

PMID- 18620927
TI  - A study of the analytical behaviour of selected new molecular entities using
      electrospray ionisation ion trap mass spectrometry, liquid chromatography, gas
      chromatography and polarography and their determination in serum at therapeutic
      concentrations.
AB  - This paper provides analytical chemical information on selected new molecular
      entities (NMEs) which are drugs that have recently been approved by the FDA.
      These are the antiretroviral drugs, atazanavir, indinavir and emtricitabine, the
      antibacterial gemifloxacin, rosuvastatine which is a cholesterol-lowering drug,
      the anti-cancer drug gefitinib and aprepitant for neurological disorders.
      Electrospray ionisation-quadrupole ion trap mass spectrometry (ESI-MS(n)) was
      employed to generate tandem mass spectrometric (MS(2)) data of the drugs studied
      and structural assignments of product ions were supported by quadrupole time-of
      flight mass spectrometry (QToF-MS/MS). These fragmentation studies were then
      utilised in the development and validation of a specific and sensitive liquid
      chromatographic method (LC-ESI-MS(2)) to identify and determine these drugs at
      therapeutic concentration levels in serum after a single protein precipitation
      procedure with acetonitrile. In addition, this method was compared to the
      application of gas liquid chromatography-flame ionisation detection (GLC-FID) and
      differential pulse polarography (DPP) for the analysis of these NMEs in serum.

PMID- 18620928
TI  - Capillary electrophoresis-chemiluminescence determination of norfloxacin and
      prulifloxacin.
AB  - A capillary electrophoresis (CE)-chemiluminescence (CL) method for determining
      norfloxacin (NFLX) and prulifloxacin (PFLX) was developed based on the enhanced
      CL intensity of the cerium(IV)-sulfite-fluoroquinolone (FQ) reaction sensitized
      by terbium(III). The separation was conducted in buffer composed of 20 mM sodium
      citrate, 4 mM citric acid and 10 mM sodium sulfite at pH 6.1. The CL reagent
      solution consisted of 2 mM cerium(IV), 4 mM terbium(III) and 1.1 mM hydrochloric
      acid. NFLX and PFLX were baseline separated within 11 min with detection limits
      (S/N=3) of 0.057 and 0.084 microg mL(-1), respectively. The maximum intra- and
      inter-day relative standard deviations (R.S.D.s) of migration time of the
      analytes were less than 4.0% and 4.2%, respectively. The proposed method was
      applied to detect NFLX and PFLX in fortified urine sample and the results were
      comparable to high-performance liquid chromatography (HPLC)-UV method. Moreover,
      the high selectivity of the CL detection and the high-separation efficiency of CE
      render the method the potential of quick analyzing fluoroquinolones in real
      complex matrix.

PMID- 18620929
TI  - Health care without (European) borders.

PMID- 18620930
TI  - Iodine deficiency--way to go yet.

PMID- 18620931
TI  - Can a student with a criminal conviction study medicine?

PMID- 18620932
TI  - Adjuvant therapy of melanoma: is pegylated interferon alfa-2b what we've been
      waiting for?

PMID- 18620933
TI  - Risking regulatory capture at the UK's Food Standards Agency?

PMID- 18620934
TI  - Five metaphors about global-health policy.

PMID- 18620935
TI  - Smokeless tobacco use by south Asian youth in the UK.

PMID- 18620936
TI  - Global health and the G8--is power just too sweet to share?

PMID- 18620938
TI  - Guineapig.

PMID- 18620939
TI  - Low bone density and decreased inhibin-B/FSH ratio in a boy treated with imatinib
      during puberty.

PMID- 18620940
TI  - Probiotic prophylaxis in predicted severe acute pancreatitis.

PMID- 18620941
TI  - Probiotic prophylaxis in predicted severe acute pancreatitis.

PMID- 18620942
TI  - Probiotic prophylaxis in predicted severe acute pancreatitis.

PMID- 18620944
TI  - Probiotic prophylaxis in predicted severe acute pancreatitis.

PMID- 18620945
TI  - Antibiotics for acute rhinosinusitis.

PMID- 18620946
TI  - Antibiotics for acute rhinosinusitis.

PMID- 18620948
TI  - Neurodevelopmental consequences of very preterm births.

PMID- 18620951
TI  - Pathogenesis and management of Paget's disease of bone.
AB  - Paget's disease of bone is a common disease characterised by focal areas of
      increased bone turnover, affecting one or several bones throughout the skeleton.
      Paget's disease is often asymptomatic but can be associated with bone pain and
      other complications such as osteoarthritis, pathological fracture, bone
      deformity, deafness, and nerve compression syndromes. Genetic factors have an
      important role in this disease, and mutations have been identified in four genes
      that cause Paget's disease and related syndromes. The most important of these is
      Sequestosome 1 (SQSTM1), which is a scaffold protein in the nuclear factor kappaB
      (NFkappaB) signalling pathway. Patients with SQSTM1 mutations have severe Paget's
      disease of bone and a high degree of penetrance with increasing age.
      Environmental factors also contribute. Most research has focused on paramyxovirus
      infection as a possible trigger, but evidence for this notion is conflicting.
      Other potential triggers include deficiency of dietary calcium and repetitive
      mechanical loading of the skeleton. Medical management of Paget's disease of bone
      is based on giving inhibitors of osteoclastic bone resorption, and
      bisphosphonates are the treatment of first choice. Bisphosphonate therapy is
      primarily indicated for patients who have bone pain arising from increased
      metabolic activity in affected bones. Bisphosphonate therapy is highly effective
      at reducing bone turnover, and it has been shown to heal radiological lesions and
      restore normal histology; however, the long-term effects of bisphosphonates on
      disease progression have not been adequately studied. No firm evidence as yet
      exists to show that bisphosphonates can prevent the development of complications
      of Paget's disease of bone, and further work is needed to address the effects of
      treatment on long-term clinical outcome.

PMID- 18620950
TI  - Effect of intermittent preventive treatment of malaria on health and education in
      schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Malaria is a major cause of morbidity and mortality in early
      childhood, yet its consequences for health and education during the school-age
      years remain poorly understood. We examined the effect of intermittent preventive
      treatment (IPT) in reducing anaemia and improving classroom attention and
      educational achievement in semi-immune schoolchildren in an area of high
      perennial transmission. METHODS: A stratified, cluster-randomised, double-blind,
      placebo-controlled trial of IPT was done in 30 primary schools in western Kenya.
      Schools were randomly assigned to treatment (sulfadoxine-pyrimethamine in
      combination with amodiaquine or dual placebo) by use of a computer-generated
      list. Children aged 5-18 years received three treatments at 4-month intervals
      (IPT n=3535, placebo n=3223). The primary endpoint was the prevalence of anaemia,
      defined as a haemoglobin concentration below 110 g/L. This outcome was assessed
      through cross-sectional surveys 12 months post-intervention. Analysis was by both
      intention to treat, excluding children with missing data, and per protocol. This
      study is registered with ClinicalTrials.gov, number NCT00142246. FINDINGS: 2604
      children in the IPT group and 2302 in the placebo group were included in the
      intention-to-treat analysis of the primary outcome; the main reason for exclusion
      was loss to follow-up. Prevalence of anaemia at 12 months averaged 6.3% in the
      IPT group and 12.6% in the placebo group (adjusted risk ratio 0.52, 95% CI 0.29
      0.93; p=0.028). Significant improvements were also seen in two of the class-based
      tests of sustained attention, with a mean increase in code transmission test
      score of 6.05 (95% CI 2.83-9.27; p=0.0007) and counting sounds test score of 1.80
      (0.19-3.41; p=0.03), compared with controls. No effect was shown for inattentive
      or hyperactive-compulsive behaviours or on educational achievement. The per
      protocol analysis yielded similar results. 23 serious adverse events were
      reported within 28 days of any treatment (19 in the IPT group and four in the
      placebo group); the main side-effects were problems of balance, dizziness,
      feeling faint, nausea, and/or vomiting shortly after treatment. INTERPRETATION:
      IPT of malaria improves the health and cognitive ability of semi-immune
      schoolchildren. Effective malaria interventions could be a valuable addition to
      school health programmes.

PMID- 18620952
TI  - Tuberculosis vaccine development: goals, immunological design, and evaluation.
AB  - A third of the world's population is infected with Mycobacterium tuberculosis,
      and 2 million people die from tuberculosis every year even though the bacille
      Calmette Guerin (BCG) vaccine has been available for more than 75 years. In order
      to reduce the immense burden of tuberculosis, new vaccines or vaccination
      strategies, or both, are urgently needed. Why BCG vaccination has not reduced
      disease prevalence, especially in the developing world, is not yet understood.
      Important contributing factors might include background immunity induced by non
      tuberculous environmental mycobacteria, diversity of BCG strains, and
      overattenuation of presently used strains. This review provides a summary of the
      immune responses thought to be important for protective tuberculosis immunity;
      various mycobacterial antigens that seem to be promising targets for vaccine
      induced immunity; different vaccination approaches being developed for use in
      people; and the key issues involved in the selection of new vaccines for expanded
      phase II or III testing.

PMID- 18620953
TI  - A deviated tongue.

PMID- 18620954
TI  - Acute kidney injury in the tropics: introduction.

PMID- 18620949
TI  - Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in
      resected stage III melanoma: final results of EORTC 18991, a randomised phase III
      trial.
AB  - BACKGROUND: Any benefit of adjuvant interferon alfa-2b for melanoma could depend
      on dose and duration of treatment. Our aim was to determine whether pegylated
      interferon alfa-2b can facilitate prolonged exposure while maintaining
      tolerability. METHODS: 1256 patients with resected stage III melanoma were
      randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627)
      6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance)
      for an intended duration of 5 years. Randomisation was stratified for microscopic
      (N1) versus macroscopic (N2) nodal involvement, number of positive nodes,
      ulceration and tumour thickness, sex, and centre. Randomisation was done with a
      minimisation technique. The primary endpoint was recurrence-free survival.
      Analyses were done by intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT00006249. FINDINGS: All randomised patients were
      included in the primary efficacy analysis. 608 patients in the interferon group
      and 613 patients in the observation group were included in safety analyses. The
      median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3.8
      33.4) months. At 3.8 (3.2-4.2) years median follow-up, 328 recurrence events had
      occurred in the interferon group compared with 368 in the observation group
      (hazard ratio 0.82, 95% CI 0.71-0.96; p=0.01); the 4-year rate of recurrence-free
      survival was 45.6% (SE 2.2) in the interferon group and 38.9% (2.2) in the
      observation group. There was no difference in overall survival between the
      groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon
      group and 60 (10%) in the observation group; grade 4 adverse events occurred in
      32 (5%) patients in the interferon group and 14 (2%) in the observation group. In
      the interferon group, the most common grade 3 or 4 adverse events were fatigue
      (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment
      with pegylated interferon alfa-2b was discontinued because of toxicity in 191
      (31%) patients. INTERPRETATION: Adjuvant pegylated interferon alfa-2b for stage
      III melanoma has a significant, sustained effect on recurrence-free survival.

PMID- 18620955
TI  - Epidemiology of acute kidney injury in Latin America.
AB  - There is little reliable information on the epidemiology of acute kidney injury
      (AKI) in Latin America. It is generally assumed that AKI in the developing world
      affects mainly young and previously healthy people, with an etiologic spectrum
      relying on particular socioeconomic and environmental conditions. Transmissible
      diseases such as leptospirosis, malaria, dengue, diarrhea, among others, are
      recognized as important causes of AKI in these areas. On the other hand, in large
      cities and university hospitals in Latin American, the AKI spectrum is similar to
      that seen in developed countries. Large studies are needed to improve our
      knowledge to design preventive strategies for this potentially lethal disease
      that affects all population subgroups, from the socially and economically
      vulnerable to the wealthy. In this article the available information regarding
      AKI epidemiology in Latin America is reviewed. Data obtained by the Latin
      American Acute Renal Failure Commission from the Latin American Society of
      Nephrology through surveys performed in 1997, 2000, and 2004 are reported.
      Finally, 3 particular medical conditions frequently associated with AKI in Latin
      America are reviewed.

PMID- 18620956
TI  - Community-acquired acute kidney injury in Asia.
AB  - Asia, the largest continent in the world, is heterogeneous in the ethnic,
      socioeconomic, and developmental status of its populations. A vast majority of it
      is poor with no adequate access to modern health care, making an accurate
      estimation of the nature and extent of acute kidney injury (AKI) difficult.
      Community-acquired AKI in otherwise healthy individuals is common, and the
      population developing AKI is younger compared with its counterparts in Europe or
      North America. The etiologic spectrum varies in different geographic regions of
      Asia depending on environmental, cultural, and socioeconomic factors. Some of the
      etiologic factors include AKI in relation to infectious diseases, intravascular
      hemolysis caused by glucose 6-phosphate dehydrogenase deficiency, poisonings
      caused by industrial chemicals or copper sulphate, animal venoms, natural
      medicines, heat stroke, and after complications of pregnancy. Preventive
      opportunities are missed because of failure to recognize the risk factors and
      early signs of AKI. Patients often present late for treatment, leading to multi
      organ involvement and increased mortality. The exact etiologic diagnosis cannot
      be established in many instances because of a lack of appropriate laboratory
      support. Modern methods of renal replacement therapy are not universally
      available; and intermittent peritoneal dialysis is still widely practiced in many
      areas.

PMID- 18620957
TI  - Epidemiology of acute kidney injury in Africa.
AB  - Acute kidney injury (AKI) is a challenging problem in Africa because of the
      burden of disease (especially human immunodeficiency virus [HIV]-related AKI in
      sub-Saharan Africa, diarrheal disease, malaria, and nephrotoxins), late
      presentation of patients to health care facilities, and the lack of resources to
      support patients with established AKI in many countries. The pattern of AKI is
      vastly different from that in more developed countries. There are no reliable
      statistics about the incidence of AKI in Africa. Infections (malaria, HIV,
      diarrheal diseases, and others), nephrotoxins, and obstetric and surgical
      complications are the major etiologies in Africa. AKI in hospitalized
      antiretroviral therapy (ART)-naive HIV-1-infected patients is associated with a 6
      fold higher risk of in-hospital mortality. The most common risk factors are
      severe immunosuppression (CD4 count, <200 cells/mm(3)) and opportunistic
      infection. The most common causes are acute tubular necrosis and thrombotic
      microangiopathy. In the post-ART era, HIV-1-infected patients with AKI still have
      an increased risk of in-hospital mortality and these episodes of AKI seem more
      frequent in the first year of ART. Subsequently, survival is comparable in those
      with and without HIV infection. More resources are required to prevent AKI and to
      provide renal support for those patients requiring dialytic therapy.

PMID- 18620958
TI  - Snakebite-induced acute kidney injury in Latin America.
AB  - There are 4 genera of venomous snakes in Latin America: Bothrops, Crotalus,
      Lachesis, and Micrurus. Acute kidney injury (AKI) has been reported consistently
      after Bothrops and Crotalus envenomations. In fact, these 2 genera of snakes are
      responsible, along with the Russell's viper, for the majority of cases of
      snakebite-induced AKI reported worldwide. Although the Bothrops snakes are the
      leading cause of venomous snakebites in Latin America, the absolute number of AKI
      cases seen after Bothrops and Crotalus snakebites is similar. In this article the
      main characteristics of Bothrops and Crotalus snakes and their venoms, the
      clinical picture, and the pattern of accidents, risk factors, and mechanisms of
      renal injury are reviewed.

PMID- 18620959
TI  - Snakebite nephrotoxicity in Asia.
AB  - Snakebites have the highest incidence in Asia and represent an important health
      problem. Clinical renal manifestations include proteinuria, hematuria,
      pigmenturia, and renal failure. Nephropathy usually is caused by bites by snakes
      with hemotoxic or myotoxic venoms. These snakes are Russell's viper, saw-scaled
      viper, hump-nosed pit viper, green pit viper, and sea-snake. Renal pathologic
      changes include tubular necrosis, cortical necrosis, interstitial nephritis,
      glomerulonephritis, and vasculitis. Hemodynamic alterations caused by vasoactive
      mediators and cytokines and direct nephrotoxicity account significantly for the
      development of nephropathy. Hemorrhage, hypotension, disseminated intravascular
      coagulation, intravascular hemolysis, and rhabdomyolysis enhance renal ischemia
      leading to renal failure. Enzymatic activities of snake venoms account for direct
      nephrotoxicity. Immunologic mechanism plays a minor role.

PMID- 18620960
TI  - Nephrotoxicity of insect and spider venoms in Latin America.
AB  - One of the most important and lethal effects of animal venoms is nephrotoxicity.
      In Latin America, severe acute kidney injury has been reported after accidents
      with poisonous arthropods such as bees, caterpillars of the genus Lonomia, and
      spiders of the genus Loxosceles. In this article the characteristics of these
      venoms, their probable mechanisms of renal damage, and the clinical picture of
      the accidents are reviewed.

PMID- 18620961
TI  - Leptospiral nephropathy.
AB  - Leptospirosis is recognized as a globally re-emerging zoonosis. Interstitial
      nephritis is the principal feature of the disease. Leptospirosis-induced acute
      kidney injury typically is nonoliguric and includes hypokalemia. Tubular function
      alterations precede a decrease in the glomerular filtration rate, which could
      explain the high frequency of hypokalemia. Studies in human beings and animals
      have shown increased urinary fractional excretion of potassium and sodium, as
      well as an increased potassium/sodium ratio, suggesting increased distal
      potassium secretion caused by increased distal sodium delivery consequent to
      functional impairment of proximal sodium reabsorption. Confirming these findings,
      Western blot studies have shown lower renal expression of the sodium/hydrogen
      exchanger isoform 3 and of aquaporin 2, together with higher renal expression of
      the Na-K-2Cl cotransporter NKCC2, in infected animals. The severe form (Weil's
      disease) manifests as diffuse alveolar hemorrhage, pulmonary edema, acute
      respiratory distress syndrome, or a combination of these features, accompanied by
      acute kidney injury and can be highly lethal. Antibiotic treatment is efficient
      in the early and late/severe phases. For critically ill leptospirosis patients,
      the following are recommended: daily hemodialysis, low daily net fluid intake
      (because of the risk for pulmonary hemorrhage), and lung-protective strategies
      (low tidal volumes and high positive end-expiratory pressures after recruitment
      maneuvers).

PMID- 18620962
TI  - Malaria and acute kidney injury.
AB  - Malaria is a major public health problem in tropical countries. About 500 million
      people suffer from malaria, leading to death in 1 to 3 million cases. Acute
      kidney injury (AKI) is one of the most dreaded complications of severe malaria.
      As per World Health Organization criteria, acute renal failure (serum creatinine
      level, > or =3 mg/dL or > or =265 micromol/L) occurs as a complication of
      Plasmodium falciparum malaria in less than 1% of cases, but the mortality rate in
      these cases may be up to 45%. It is more common in adults than children. Renal
      involvement varies from mild proteinuria to severe azotemia associated with
      metabolic acidosis. It may be oliguric or nonoliguric. AKI may be present as a
      component of multi-organ dysfunction or as a lone complication. The prognosis in
      the latter is generally better. Several pathogenic mechanisms interplay for the
      clinical manifestation. The predominant lesions are acute tubular necrosis and
      mild proliferative glomerulonephropathy. These patients do not progress to
      chronic kidney disease. The management of malaria-induced AKI includes
      appropriate antimalarials (parenteral artesunate or quinine), fluid electrolyte
      management, and renal replacement therapy at the earliest. The use of diuretics
      should be avoided.

PMID- 18620963
TI  - Viral hemorrhagic fever-induced acute kidney injury.
AB  - Viral hemorrhagic fevers (VHFs) are diseases caused by the RNA virus from 4
      different families (Flaviridiae, Arenaviridae, Bunyaviridae, and Filoviridae)
      that are acquired through the bite of an infected arthropod or by the inhalation
      of particles of rodent excreta. Among the VHFs, dengue and yellow fever are the
      most prevalent in tropical regions worldwide. The clinical presentation is
      characterized by fever, malaise, increased vascular permeability, and coagulation
      defects that can result in bleeding. Acute kidney injury is an uncommon
      complication but renal dysfunction has been associated with various VHFs. In this
      article we review the renal manifestations of dengue and yellow fever infections.

PMID- 18620964
TI  - Natural medicines causing acute kidney injury.
AB  - The use of alternative remedies derived from plants and animals is increasing
      worldwide. Their source and composition varies depending on the prevalent local
      practices. They are not tested for efficacy and safety; their ingredients are
      unknown and the dosage and route of administration are not standardized.
      Potentially toxic chemicals are added to them to increase their potency and
      mistaken identity has led to the use of toxic plants instead of the originally
      intended herb. Kidneys play a vital role in the metabolism and excretion of these
      substances and acute kidney injury is a common and important manifestation of
      their toxicity. The most usual renal lesions include acute tubular necrosis,
      cortical necrosis, and interstitial nephritis. Patients often present late to
      hospitals with multi-organ involvement. The diagnosis may be missed if the
      history is not sought specifically. These factors culminate in high mortality
      rates. Study of this entity is difficult because of the remoteness of the areas,
      unfamiliarity with local cultures, and mystery and secrecy surrounding the
      natural medicines used. Physicians need to be aware of this condition to make a
      timely diagnosis and provide appropriate management. Public awareness and
      regulation of the use of these medicines are required to eradicate this entity
      from the community.

PMID- 18620965
TI  - A review of microbial injury and recovery methods in food.
AB  - The existence of injured microorganisms in food and their recovery during
      culturing procedures is critical. Microbial injury is characterized by the
      capability of a microorganism to return to normalcy during a resuscitation
      process in which the damaged essential components are repaired. Injury of
      microorganisms can be induced by sublethal heat, freezing, freeze-drying, drying,
      irradiation, high hydrostatic pressure, aerosolization, dyes, sodium azide,
      salts, heavy metals, antibiotics, essential oils, sanitizing compounds, and other
      chemicals or natural antimicrobial compounds. Injured microorganisms present a
      potential threat in food safety since they may repair themselves under suitable
      conditions. Detection of injured microorganisms can be important to practical
      interpretations of data in food microbiology. This review provides an overview of
      microbial injury in food and discusses the development of recovery methods for
      detecting injured foodborne microorganisms.

PMID- 18620966
TI  - Recent advances in molecular techniques to study microbial communities in food
      associated matrices and processes.
AB  - In the last two decades major changes have occurred in how microbial ecologists
      study microbial communities. Limitations associated with traditional culture
      based methods have pushed for the development of culture-independent techniques,
      which are primarily based on the analysis of nucleic acids. These methods are now
      increasingly applied in food microbiology as well. This review presents an
      overview of current community profiling techniques with their (potential)
      applications in food and food-related ecosystems. We critically assessed both the
      power and limitations of these techniques and present recent advances in the
      field of food microbiology attained by their application. It is unlikely that a
      single approach will be universally applicable for analyzing microbial
      communities in unknown matrices. However, when screening samples for well-defined
      species or functions, techniques such as DNA arrays and real-time PCR have the
      potential to overtake current culture-based methods. Most importantly, molecular
      methods will allow us to surpass our current culturing limitations, thus
      revealing the extent and importance of the 'non-culturable' microbial flora that
      occurs in food matrices and production.

PMID- 18620967
TI  - Inhibition of Bacillus cereus and Bacillus weihenstephanensis in raw vegetables
      by application of washing solutions containing enterocin AS-48 alone and in
      combination with other antimicrobials.
AB  - Enterocin AS-48 is a broad-spectrum cyclic antimicrobial peptide produced by
      Enterococcus faecalis. In the present study, the bacteriocin was tested alone and
      in combination with other antimicrobials for decontamination of Bacillus
      inoculated on alfalfa, soybean sprouts and green asparagus. Washing with
      enterocin AS-48 solutions reduced viable cell counts of Bacillus cereus and
      Bacillus weihenstephanensis by 1.0-1.5 and by 1.5-2.38 log units right after
      application of treatment, respectively. In both cases, the bacteriocin was
      effective in reducing the remaining viable population below detection levels
      during further storage of the samples at 6 degrees C, but failed to prevent
      regrowth in samples stored at 15 or 22 degrees C. Application of washing
      treatments containing enterocin AS-48 in combination with several other
      antimicrobials and sanitizers (cinnamic and hydrocinnamic acids, carvacrol,
      polyphosphoric acid, peracetic acid, hexadecylpyridinium chloride and sodium
      hypochlorite) greatly enhanced the bactericidal effects. The combinations of AS
      48 and sodium hypochlorite, peracetic acid or hexadecylpyridinium chloride
      provided the best results. After application of the combined treatments on
      alfalfa sprouts contaminated with B. cereus or with B. weihenstephanensis, viable
      bacilli were not detected or remained at very low concentrations in the treated
      samples during a 1-week storage period at 15 degrees C. Inhibition of B. cereus
      by in situ produced bacteriocin was tested by cocultivation with the AS-48
      producer strain E. faecalis A-48-32 inoculated on soybean sprouts. Strain A-48-32
      was able to grow and produce bacteriocin on sprouts both at 15 and 22 degrees C.
      At 15 degrees C, growth of B. cereus was completely inhibited in the cocultures,
      while a much more limited effect was observed at 22 degrees C. The results
      obtained for washing treatments are very encouraging for the application of
      enterocin AS-48 in the decontamination of sprouts. Application of washing
      treatments containing AS-48 alone can serve to reduce viable cell counts of
      bacilli in samples stored under refrigeration, while application of combined
      treatments should be recommended to avoid proliferation of the surviving bacilli
      under temperature-abuse conditions.

PMID- 18620968
TI  - Detection and identification of wild yeasts in Champus, a fermented Colombian
      maize beverage.
AB  - The aim of this study was to identify and characterise the predominant yeasts in
      Champus, a traditional Colombian cereal-based beverage with a low alcoholic
      content. Samples of Champus from 20 production sites in the Cauca Valley region
      were analysed. A total of 235 yeast isolates were identified by conventional
      microbiological analyses and by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) of ITS1-5.8S rDNA-ITS2. The dominant species were:
      Saccharomyces cerevisiae, Issatchenkia orientalis, Pichia fermentans, Pichia
      kluyveri var. kluyveri, Zygosaccharomyces fermentati, Torulospora delbruekii,
      Galactomyces geotrichum and Hanseniaspora spp. Model Champus systems were
      inoculated with single strains of some isolated sporogenus species and the
      aromatic profiles were analysed by SPME. Analysis of data showed that Champus
      strains produced high amounts of esters. The aromatic compounds produced by
      Saccharomyces and non-Saccharomyces yeasts from Champus can exert a relevant
      influence on the sensory characteristics of the fermented beverage. The Champus
      strains could thus represent an important source for new yeast biotypes with
      potential industrial applications.

PMID- 18620969
TI  - Rational selection of non-Saccharomyces wine yeasts for mixed starters based on
      ester formation and enological traits.
AB  - Thirty-eight yeast strains belonging to the genera Candida, Hanseniaspora,
      Pichia, Torulaspora and Zygosaccharomyces were screened for ester formation on
      synthetic microbiological medium. The genera Hanseniaspora and Pichia stood out
      as the best acetate ester producers. Based on the ester profile Hanseniaspora
      guilliermondii 11027 and 11102, Hanseniaspora osmophila 1471 and Pichia
      membranifaciens 10113 and 10550 were selected for further characterization of
      enological traits. When growing on must H. osmophila 1471, which displayed a
      glucophilic nature and was able to consume more than 90% of initial must sugars,
      produced levels of acetic acid, medium chain fatty acids and ethyl acetate,
      within the ranges described for wine. On the other hand, it was found to be a
      strong producer of 2-phenylethyl acetate. Our data suggest that H. osmophila 1471
      is a good candidate for mixed starters, although the possible interactions with
      S. cerevisiae deserve further research.

PMID- 18620970
TI  - Microbiological characterisation of Robiola di Roccaverano cheese using PCR-DGGE.
AB  - The aim of this study was the microbiological characterisation of a typical
      Italian cheese "Robiola di Roccaverano" with Protected Designation of Origin
      (PDO). Fresh and ripened robiola samples were collected from four artisanal and
      one industrial producer. Artisanal producers used raw goat's milk and natural
      fermentation, whilst the industrial producer used mixed cow-goat's milk and
      selected starters. The microbial communities were monitored during different
      seasons and ripening times with PCR-DGGE and culture-dependent methods. The
      cluster analysis showed that the DGGE bacterial patterns were related to the
      different manufacturing and climatic conditions, revealing the occurrence of
      species associated to Robiola di Roccaverano. The DGGE profiles of yeasts were
      affected by ripening in summer season. Moreover, the results obtained allowed the
      identification of microbial species such as Lactococcus lactis subsp. lactis,
      Geotricum spp. and Kluyveromyces lactis that are related to the production of
      this typical cheese.

PMID- 18620971
TI  - Viability of multi-strain mixtures of Listeria monocytogenes, Salmonella
      typhimurium, or Escherichia coli O157:H7 inoculated into the batter or onto the
      surface of a soudjouk-style fermented semi-dry sausage.
AB  - The fate of Listeria monocytogenes, Salmonella typhimurium, or Escherichia coli
      O157:H7 were separately monitored both in and on soudjouk. Fermentation and
      drying alone reduced numbers of L. monocytogenes by 0.07 and 0.74 log(10)CFU/g
      for sausages fermented to pH 5.3 and 4.8, respectively, whereas numbers of S.
      typhimurium and E. coli O157:H7 were reduced by 1.52 and 3.51 log(10)CFU/g and
      0.03 and 1.11 log(10)CFU/g, respectively. When sausages fermented to pH 5.3 or
      4.8 were stored at 4, 10, or 21 degrees C, numbers of L. monocytogenes, S.
      typhimurium, and E. coli O157:H7 decreased by an additional 0.08-1.80, 0.88-3.74,
      and 0.68-3.17 log(10)CFU/g, respectively, within 30 days. Storage for 90 days of
      commercially manufactured soudjouk that was sliced and then surface inoculated
      with L. monocytogenes, S. typhimurium, and E. coli O157:H7 generated average D
      values of ca. 10.1, 7.6, and 5.9 days at 4 degrees C; 6.4, 4.3, and 2.9 days at
      10 degrees C; 1.4, 0.9, and 1.6 days at 21 degrees C; and 0.9, 1.4, and 0.25 days
      at 30 degrees C. Overall, fermentation to pH 4.8 and storage at 21 degrees C was
      the most effective treatment for reducing numbers of L. monocytogenes (2.54
      log(10)CFU/g reduction), S. typhimurium (> or =5.23 log(10)CFU/g reduction), and
      E. coli O157:H7 (3.48 log(10)CFU/g reduction). In summary, soudjouk-style sausage
      does not provide a favorable environment for outgrowth/survival of these three
      pathogens.

PMID- 18620972
TI  - Inhibitory effects of polyphosphates on Clostridium perfringens growth,
      sporulation and spore outgrowth.
AB  - This study evaluated the effects of various polyphosphates (SPP, STPP, SAPP and
      TSPP) on growth, sporulation and spore germination of Clostridium perfringens,
      and germination and outgrowth of C. perfrinegns spores in poultry meat. We have
      found that the requirements of polyP (0.8-1.0%) to inhibit C. perfringens
      bacterial growth were higher than those reported for other bacteria. Sub-lethal
      concentrations of polyP significantly (p<0.01) inhibited sporulation of C.
      perfringens by reducing sporulating cells (heat-resistant cells) approximately 5
      6 log(10). While C. perfringens spores were able to germinate in the presence of
      1% STPP, their outgrowth was significantly (p<0.01) inhibited. Finally, a
      significant (p<0.01) reduction of survival of C. perfringens was observed when
      meat samples contaminated with a cocktail of spores of C. perfringens isolates
      carrying enterotoxin gene on the chromosome were treated with 1% STPP.
      Collectively, this study demonstrated the inhibitory effects of polyP on growth,
      sporulation and spore outgrowth of C. perfringens, and suggests that polyP can be
      used not only as an enhancer of the functional properties of meat products, but
      also as a promising C. perfringens antimicrobial agent.

PMID- 18620973
TI  - Disinfection potential of ozone, ultraviolet-C and their combination in wash
      water for the fresh-cut vegetable industry.
AB  - The purpose of this research was to investigate the disinfection efficacy of
      ozone (O(3)) and UV-C illumination (UV), and their combination (O(3)-UV) for
      reducing microbial flora of fresh-cut onion, escarole, carrot, and spinach wash
      waters collected from the industry. Furthermore, the influence of water
      physicochemical parameters on the decontamination efficacy and the effect of
      these technologies on physicochemical quality of wash water were analyzed. O(3),
      UV, and O(3)-UV were effective disinfection treatments on vegetable wash water,
      with a maximum microbial reduction of 6.6 log CFU mL(-1) after 60 min treatment
      with O(3)-UV. However, maximum total microbial reductions achieved by UV and O(3)
      treatments after 60 min were 4.0 and 5.9 log CFU mL(-1), lower than by O(3)-UV
      treatment. Furthermore, turbidity of wash water was reduced significantly by O(3)
      and O(3)-UV treatments, while UV treatment did not affect the physicochemical
      quality of the water. Conclusions derived from this study illustrate that O(3)
      and O(3)-UV are alternatives to other sanitizers used in the fresh-cut washing
      processes. The use of these technologies would allow less frequent changing of
      spent water and the use of much lower sanitizer doses. Nevertheless, in specific
      applications such as carrot wash water, where levels of undesirable microbial and
      chemical constituents are lower than other vegetable wash water, UV treatment
      could be an appropriate treatment considering cost-effectiveness criteria.

PMID- 18620974
TI  - Reduction of soybean oligosaccharides and properties of alpha-D-galactosidase
      from Lactobacillus curvatus R08 and Leuconostoc mesenteroides [corrected] JK55.
AB  - This study was undertaken to investigate the potential for reducing non-digestive
      oligosaccharides (NDO) in soy foods, as well as the influence of exogenous
      conditions on intracellular alpha-galactosidase (alpha-Gal) producing lactic acid
      bacteria. Two strains, Lactobacillus curvatus R08 and Leuconostoc mesenteroides
      [corrected]JK55, showed the highest levels of raffinose degrading activity at
      over 40 U mL(-1), and presented maximum activities during the stationary phase in
      a medium where raffinose was the only carbon source. Raffinose was the most
      effective inducer, followed by melibiose, and galactose; the enzymes were
      partially inhibited by fructose and sucrose. On the other hand, limited activity
      was observed in glucose. The strains displayed optimum activity levels at neutral
      pH and a 35-37 degrees C temperature range. The alpha-Gal activities of L.
      curvatus R08 and Leu. mesenteroides [corrected] JK55 were maintained at pH 6.5
      10.0. The activity of the alpha-Gal enzyme was stable in a relatively broad range
      of temperatures from 0 to 40 degrees C for 3h. In soymilk, Leu. mesenteroides
      [corrected] JK55 and L. curvatus R08 completely hydrolyzed the NDO after 18-24h
      of fermentation. The abilities of L. curvatus R08 and Leu. mesenteroides
      [corrected] JK55 to degrade raffinose sugars and, particularly, to produce
      organic acids from sugar, could contribute to reductions in the anti-nutritional
      properties of soy, and to the accumulation of compounds with beneficial
      properties during food processing. Furthermore, this study provides the optimum
      conditions to induce alpha-Gal from these strains.

PMID- 18620975
TI  - Detection and molecular characterization of Vibrio parahaemolyticus isolated from
      seafood harvested along the southwest coast of India.
AB  - The levels of total and tdh(+)Vibrio parahaemolyticus were estimated in 83
      seafood samples from southwest coast of India by colony hybridization.
      Conventional enrichment and isolation technique was also used to study the
      prevalence. Polymerase chain reaction (PCR) was performed on bacterial cell
      lyates for detection of total and pathogenic V. parahaemolyticus by amplification
      of specific genes. Of 83 samples tested, V. parahaemolyticus could be detected in
      74 (89.2%) samples and tdh(+)V. parahaemolyticus in 5 (6.0%) samples by colony
      hybridization. V. parahaemolyticus was detected in 68 (81.9%) of 83 samples after
      18 h of enrichment by PCR, and isolated from 63 (75.9%) of 83 samples by
      conventional isolation. The virulence genes tdh and trh could be detected in 8.4%
      and 25.3%, respectively, in the sample enrichment broths by PCR. Use of colony
      hybridization following enrichment to achieve sensitive detection of tdh(+)V.
      parahaemolyticus in seafood was evaluated using another set of 58 seafood
      samples. Thirty pathogenic V. parahaemolyticus strains isolated during the study
      were screened by PCR for genetic markers to be specific for the detection of the
      pandemic clone. Results of this study suggest that the GS-PCR may serve as a
      reliable genetic marker for the pandemic clone of V. parahaemolyticus.

PMID- 18620976
TI  - Present knowledge of the bacterial microflora in the extreme environment of sugar
      thick juice.
AB  - The diversity of the bacterial population in sugar thick juice, an intermediate
      product in the production of beet sugar, which exhibits an extreme, osmophilic
      environment with a water activity value (a(w)) less than 0.86, was assessed with
      both culture-dependent and -independent 16S ribosomal RNA (rRNA) gene-based
      analyses. In comparison with previous studies, the number of different thick
      juice bacterial species increased from 29 to 72. Remarkably, a limited, gram
      positive, culturable flora, encompassing species of Bacillus, Staphylococcus and
      mainly Tetragenococcus dominated thick juice during storage, while a more
      heterogeneous and unculturable fraction of Acinetobacter, Sporolactobacillus and
      Thermus species could be detected in freshly produced thick juice. Notably,
      almost all bacteria detected in the thick juice were also detected in the air,
      emphasising the importance of further investigation and assessment of strategies
      to reduce (air) contamination during processing and storage. The discovery of the
      contamination source may be used for the development of management strategies for
      thick juice degradation resulting from microbial activity.

PMID- 18620977
TI  - Male Facial Rejuvenation. Preface.

PMID- 18620978
TI  - Aging changes in the male face.
AB  - Discrete anatomic differences exist between the male and female face that are
      relevant in surgical planning. Although the aging process of male and female
      faces share many common features, attention to the particular differences in the
      aging man is warranted. Gender differences in the male face include the presence
      of facial hair, increased facial vascularity, increased thickness, increased
      sebaceous content, hormonal influences, and potentially differing rates of fat
      and bone absorption during the life cycle. This article describes the anatomic
      characteristics of the male face that require attention as the facial plastic
      surgeon constructs a treatment plan for the aging face Further investigation is
      required to describe in more detail the anatomic and biologic differences in male
      and female facial aging.

PMID- 18620979
TI  - Considerations in male aging face consultation: psychologic aspects.
AB  - Historically, the male cosmetic surgery patient has been viewed as being highly
      psychopathologic. Recent studies have refuted this longheld belief. However, when
      conducting a male aging face consultation, it is important for cosmetic surgeons
      to perform a focused psychiatric assessment to screen for mentally-ill patients,
      who may not be good surgical candidates. Included in the spectrum of psychiatric
      diseases that should be recognized is body dysmorphic disorder, an illness
      characterized by distortions in body perception, which has a higher prevalence in
      the cosmetic surgery population. By taking a focused psychiatric history, the
      cosmetic surgeon can identify patients who have untreated psychiatric pathology
      and are not psychologically appropriate for surgery. These patients would instead
      benefit from consultation with a mental health professional.

PMID- 18620980
TI  - Hair restoration.
AB  - The impact of male hair loss as a personal and social marker of aging is
      tremendous and its persistence as a human concern throughout recorded history
      places it in the forefront of male concern about the physical signs of aging.
      Restoration of the frontal hairline has the visual effect of re-establishing
      facial symmetry and turning back time. Follicular unit transplantation has
      revolutionized hair restoration, with its focus on redistributing large numbers
      of genetically stable hair to balding scalp in a natural distribution. Follicular
      unit hair restoration surgery is a powerful tool for the facial plastic surgeon
      in male aesthetic facial rejuvenation because it offers high-impact, natural
      appearing results with minimal downtime and risk for adverse outcome.

PMID- 18620981
TI  - Rejuvenation of the male brow.
AB  - Rejuvenation of the brow is an integral component of surgery of the aging face.
      Browlifting in men poses challenges that are different from surgery on the female
      brow. The ideal shape of the brow in men is distinct from the shape of the female
      brow. The male hairline is often elevated or receding. Male skin is generally
      heavier, thicker, and coarser. Men generally have deeper furrows and creases. The
      purpose of this article is to delineate an approach that achieves optimal
      rejuvenation of the upper one third of the face in the male patient.

PMID- 18620982
TI  - Management of the lower lid in male blepharoplasty.
AB  - Rejuvenation of the lower eyelid blepharoplasty in men requires consideration of
      different esthetic norms than those considered in women. Although both require a
      thorough understanding of anatomy, and the process of aging in each includes
      descent of the globe, pseudoherniation of the orbital fat, and skeletonization of
      the inferior bony rim, the goals for male blepharoplasty differ. The authors
      review the primary surgical approaches in lower lid blepharoplasty
      (transconjunctival skin-muscle flap) and the currently described techniques used
      to address displaced orbital fat, with special consideration of the male patient.

PMID- 18620983
TI  - Midcheek and lower face/neck rejuvenation in the male patient.
AB  - Rejuvenation of the mid- and lower face in the male patient can be challenging.
      Historically, most of these procedures were performed on female patients.
      However, an increasing number of men are seeking rejuvenative procedures and
      because of this trend, it is imperative that facial plastic surgeons become
      facile with the nuances of male mid- and lower facial rejuvenation. Failing to
      understand the important differences between male and female patients can lead to
      pitfalls during the perioperative period. The conscientious surgeon should be
      mindful of these differences, beginning with the male cosmetic consultation and
      proceeding through to the postoperative period. The goal of this article is to
      review the principles of male mid- and lower facial rejuvenation.

PMID- 18620984
TI  - Aging male rhinoplasty.
AB  - Americans over the age of 65 represent one of the fastest growing segments of our
      population. Rhinoplasty in the elderly man presents a unique set of obstacles. In
      addition to the typical forces of healing and scar contracture, the aging nose
      features the altered anatomy and physiology of aging added to an already
      complicated three-dimensional structure. The heavier, thicker, and more sebaceous
      skin of men can exacerbate the loss of support associated with aging, creating a
      scenario of worse functional issues in men as compared with their female
      counterparts. Approaching the aging nose requires an appreciation of the nuances
      of the preoperative, intraoperative, and postoperative phases of the patient
      interaction. Although functional issues predominate in this population, aesthetic
      concerns also need to be addressed.

PMID- 18620985
TI  - Male skin care needs.
AB  - Male skin care has undergone significant development over the past decade, with
      many companies now marketing skin care products directly to the male consumer.
      Despite the claims of many of these companies, few over-the-counter products have
      data to support their efficacy at a clinical level. A basic, effective regimen
      for preventive male skin care should include twice-daily facial cleansing and
      twice-daily moisturizer application, which should include sunscreen during the
      day. This article focuses on topical therapies directed at the maintenance and
      repair of photoaged male skin. The future holds promise for new developments in
      skin care. However, in the absence of significant scientific breakthroughs, the
      most cost-effective intervention will continue to be prevention.

PMID- 18620986
TI  - Injectables and fillers in male patients.
AB  - Traditionally, in facial plastic surgery, male patients were known to focus on
      function over form. Men typically did not consider rejuvenation surgery until
      they had advanced changes associated with aging, and it was often coupled with a
      functional concern. However, over the last several years, the number of men
      seeking minimally invasive cosmetic products, such as dermal fillers and
      injectables, has increased significantly. Motives include the desire to be more
      competitive and youthful in the workforce, the growing social acceptability of
      cosmetic procedures, and increased awareness of nonsurgical options. The optimal
      use of these products and procedures requires appropriate patient selection,
      knowledge of the products, and a thorough understanding of the regional anatomy
      and clinical applications.

PMID- 18620987
TI  - Facial resurfacing of the male patient.
AB  - Cosmetic facial plastic procedures, surgical and nonsurgical alike, continue to
      increase in number. Recent statistics from the American Society of Aesthetic
      Plastic Surgery indicate that approximately 78% of the nearly 8.3 million
      cosmetic procedures performed in the United States each year are nonsurgical.
      Similar statistics have been demonstrated by the American Academy of Facial
      Plastic and Reconstructive Surgery who report that over the past 5 years there
      has been a 47% increase in nonsurgical procedures compared with a 19% increase in
      surgical procedures. The demographic of those seeking cosmetic procedures is
      dramatically changing also. Although cosmetic surgery was once predominantly
      sought by females, more and more male patients are now seeking treatment.

PMID- 18620988
TI  - Amyloidosis of seminal vesicles and ejaculatory ducts: a histologic analysis of
      21 cases among 447 prostatectomy specimens.
AB  - To investigate the incidence of amyloidosis of seminal vesicles and ejaculatory
      system including ejaculatory ducts and vasa deferentia, we reviewed the whole
      mount sections of 447 radical prostatectomy specimens removed for prostatic
      cancer, including 273 cases from the United States and 174 cases from Korea. Of
      these, 21 cases (4.7%) showed amyloidosis in seminal vesicles, vasa deferentia,
      and in ejaculatory ducts. Ten of these (3.7%) cases were from the United States
      and 11 cases (6.3%) from Korea. The patients' age ranged from 51 to 79 years
      (mean, 66.1 years). Amyloid deposition was found in 5 patients in the sixth
      decade (3.4%), 9 patients in the seventh decade (4.7%), and 7 patients in the
      eighth decade (9.3%). At the seventh decade of life, the Korean patients showed a
      higher incidence (8.3%) than American patients (2.5%), but other age groups
      showed no difference. All cases showed bilateral involvement of the seminal
      vesicles and ejaculatory systems. The deposits of amyloid tended to be nodular
      and affected the subepithelial region of seminal vesicles, vasa deferentia, and
      ejaculatory ducts. There was no amyloid deposit around blood vessels or in the
      prostatic parenchyma. Localized amyloidosis of the ejaculatory system involves
      not only the seminal vesicles but also the vasa deferentia and the ejaculatory
      ducts. The vessels or prostatic stroma are not part of this process. Amyloidosis
      develops subepithelially spreading to include the wall of these organs and
      appears to be related to advanced age. The incidence of amyloidosis of the
      ejaculatory system in Korean patients was higher than in US patients.

PMID- 18620989
TI  - Clinicopathologic profile of 470 giant cell tumors of bone from a cancer hospital
      in western India.
AB  - Over 20 years, 470 cases of giant cell tumor of bone diagnosed at a tertiary
      cancer hospital were analyzed. Male predominance (57%), predilection for bones
      around the knee joint (42%), and occurence in the 21- to 30-year-old age group
      (49.1%) with 6% being in the immature skeleton are well known facts. Accurate
      diagnosis was possible in 66% and 88% of cases on radiology and biopsy,
      respectively. Tumors measured 6 to 20 cm and, in 402 cases, showed "usual"
      histology comprising uniformly scattered multinucleate giant cells amidst
      mononuclear stromal cells, together imparting a syncitium-like appearance.
      Presence of osteoid, hemorrhage, and aneurysmal bone cyst-like areas; spindle
      cells in sheets (devoid of giant cells); or storiform pattern and intravascular
      osteoclasts were less common. The less common histologic features posed
      diagnostic difficulty in the setting of a small biopsy. Treatment included
      intralesional curettage (33.19%), marginal excision (4.2%), wide excision (31%),
      or radical surgeries (14.25%). Recurrences seen in 170 cases were multiple in 47
      cases. Metastases largely to the lung were recorded in 24 cases. The histology of
      all the tumors, namely, primary, recurrent, or metastatic was identical.
      Statistical analysis using the computer software SPSS (SPSS Inc, Chicago, Ill)was
      performed with particular reference to the unusual histologic features vs
      recurrence and metastasis by chi(2) test. The only statistically significant
      factors were occurrence in the axial skeleton vs appendicular skeleton (P = .001)
      and primary treatment elsewhere vs at this hospital (P = .045), each of these
      being associated with increased frequency for local recurrence but not
      metastasis.

PMID- 18620990
TI  - Lymphoglandular bodies in malignant tumors: with special reference to histologic
      specimens.
AB  - Lymphoglandular bodies (LGBs) have been described as cytoplasmic fragments of
      lymphocytes and a specific feature of organized lymphoid tissue. The recognition
      of LGBs is useful in distinguishing malignant lymphomas from carcinomas and
      sarcomas in cytology specimens, especially in Giemsa-stained tissues. So far,
      there has been no description of LGBs in hematoxylin and eosin (HE)-stained
      histologic specimens in the literature. Therefore, we evaluated LGBs in HE
      sections, especially regarding malignant tumors. We reviewed 110 biopsy and
      surgical materials including malignant lymphoma, carcinoma, and other malignant
      tumors and evaluated the frequency, number, size, and significance of LGBs. We
      also performed the terminal deoxyribosyl transferase-mediated dUTP-biotin nick
      end labeling (TUNEL) method on LGBs. Lymphoglandular bodies were found in about
      40% of cases with malignant lymphoma, whereas only 3 (3.8%) nonlymphoma cases
      showed LGBs. These were undifferentiated carcinoma, seminoma, and multiple
      myeloma. The size of LGBs was usually less than half the size of a red blood
      cell. No apoptotic cells were detected in any of the cases by TUNEL method
      regarding LGBs. Our study suggests that LGBs can be found in HE sections. As
      observed in cytologic specimens in the literature, the presence of LGBs around
      cytologically malignant cells favors a diagnosis of malignant lymphoma rather
      than nonlymphoma malignancies, even in HE histologic sections.

PMID- 18620991
TI  - The foamy variant of pancreatic intraepithelial neoplasia.
AB  - Foamy gland adenocarcinoma is a variant of pancreatic ductal carcinoma, whose
      precursor has not been described. We describe here the morphologic and
      immunohistochemical features of the pancreatic intraepithelial neoplasia (PanIN)
      lesions associated with invasive foamy pancreatic adenocarcinoma. The staining
      properties and morphologic and immunohistochemical features of 3 foamy PanIN
      lesions were compared with those of 7 pancreatic foamy gland adenocarcinomas.
      Hematoxylin and eosin, Mayer mucicarmine, periodic acid-Schiff, and Alcian blue
      stains were available for review in all cases. Immunohistochemical labeling for
      cytokeratin (CK)7, CK20, carcinoembryonic antigen polyclonal, MUC1, MUC2, CDX2,
      p53, and cyclin D1 was performed. The PanIN-1 lesions were found in the
      nonneoplastic pancreas and were similar to the PanIN-1 lesions of ordinary
      pancreatic ductal carcinoma. The PanIN-2 and -3 lesions were recognized
      immediately adjacent to or within the invasive foamy gland carcinoma. In these
      lesions, small or markedly dilated ducts were lined by cuboidal and columnar
      dysplastic nonfoamy cells and foamy cells. Hobnail cells were present in 2 cases.
      The PanIN-1, 2, and 3 lesions and the invasive foamy gland adenocarcinomas
      stained with mucicarmine, periodic acid-Schiff, and Alcian blue. The 3 PanIN-2
      and -3 lesions and all 7 invasive foamy adenocarcinomas labeled with CK7,
      carcinoembryonic antigen polyclonal, and MUC1, whereas only 2 PanIN-2 and -3
      lesions and 5 invasive adenocarcinomas showed immunoreactivity for cyclin D1 and
      p53. Three distinctive foamy PanIN lesions were identified within 7 invasive
      foamy gland pancreatic adenocarcinomas. The gradual progression of cytological
      and architectural abnormalities of the PanIN lesions from PanIN-1 to PanIN-3
      excludes neoplastic ductal spread. These foamy PanIN lesions probably represent
      cancer precursors.

PMID- 18620992
TI  - Cdx2, cytokeratin 20, thyroid transcription factor 1, and prostate-specific
      antigen expression in unusual subtypes of prostate cancer.
AB  - There are some unusual histologic variants of prostate carcinoma, including
      mucinous, signet-ring cells, and ductal carcinomas that can metastasize in a
      problematic way and simulate lung, colorectal, or bladder primaries. Currently,
      antibodies that are organ-specific have been used in the routine surgical
      pathology practice. Our aim is to study the profile of expression of Cdx2,
      thyroid transcription factor 1 (TTF1), and cytokeratin 20 (CK20) in prostate
      cancer with unusual histologic finding. Twenty-nine prostate adenocarcinomas with
      unusual histologic findings were submitted to immunohistochemistry with prostate
      specific antigen (PSA), CK20, Cdx2, and TTF1 antibodies. There were 7 mucinous, 5
      ductal, 2 signet-ring cells, and 15 usual acinar adenocarcinomas with focal
      mucinous differentiation. To compare the results with usual acinar
      adenocarcinomas, we studied 10 primary and their respective lymph node metastases
      in a tissue microarray, 2 unusual metastatic adenocarcinomas, and 6 usual acinar
      high-grade carcinomas. For tumors with special histologic finding, Cdx2 was
      expressed by 9 (31.0%) mucinous, signet-cell, or with focal mucinous
      differentiation. Thyroid transcription factor 1 was moderately positive in
      mucinous differentiation areas of 2 (6.9%) adenocarcinomas. Cytokeratin 20 was
      expressed by 9 (31.0%) tumors, among them, 3 ductal adenocarcinomas. Prostate
      specific antigen was positive in 28 (96.6%) cases and negative in 1 ductal
      adenocarcinoma. There was only 1 worrisome ductal adenocarcinoma that was
      strongly CK20 positive and PSA negative. Almost one third of mucinous prostate
      carcinomas express Cdx2. Cytokeratin 20 can be positive also in one third of
      prostate carcinomas, especially the ductal type. Pathologist should be alert when
      evaluating immunohistochemical profiles of unusual histologic findings of
      prostate cancer, mostly in distant sites.

PMID- 18620993
TI  - Eosinophilic angiocentric fibrosis of the sinonasal tract.
AB  - Eosinophilic angiocentric fibrosis (EAF) is an uncommon inflammatory fibrosing
      lesion of the upper respiratory tract and orbit that occurs mainly in young to
      middle-aged women. The etiology of EAF is unknown. To our knowledge,
      approximately 28 cases have been previously reported in the English literature.
      We report here 3 additional cases of EAF of the sinonasal tract; 2 in women aged
      19 and 31 years, and 1 in a man aged 49 years. The 19-year-old woman is the
      youngest patient with EAF ever described. The patients presented with a nasal
      cavity mass, face pain, or nasal obstructive symptoms of long duration.

PMID- 18620994
TI  - Interstitial cells of Cajal in chagasic megaesophagus.
AB  - Chagasic visceromegalies are the most important digestive manifestations of
      Chagas disease and are characterized by motor disorders and dilation of organs
      such as esophagus and colon. One of the theories raised to explain the
      physiopathogenesis of chagasic megas is the plexus theory. Recent studies have
      shown a reduction of interstitial cells of Cajal (ICCs) in the colon of chagasic
      patients. These cells are present throughout the gastrointestinal tract and are
      considered to be pacemaker cells, that is, they are responsible for coordinating
      peristalsis and for mediating nerve impulses. In view of the lack of studies on
      these cells in megaesophagus and the previous observation of a reduction of ICCs
      in chagasic megacolons, we compared the distribution of ICCs in the esophagus of
      chagasic and nonchagasic patients to contribute to a better understanding of the
      physiopathogenesis of this esophageal disease. Esophageal biopsy samples from 10
      chagasic and 5 nonchagasic patients were used. Cells were identified with the
      anti-CD117 antibody. The number of ICCs was quantified in longitudinal and
      circular muscle layers and myenteric plexus. The results were analyzed
      statistically by comparison of means. An intense reduction in the number of ICCs
      was observed in muscle layers and in the myenteric plexus of patients with
      megaesophagus. We conclude that there is an intense reduction of ICCs in the
      esophagus of chagasic patients when compared to nonchagasic patients, a finding
      supporting the important role of these cells in gastrointestinal tract motility.
      A deficiency in these cells might be implied in the genesis of megaesophagus.

PMID- 18620995
TI  - Phosphatase and tensin homologue and pituitary tumor-transforming gene in
      pituitary adenomas. Clinical-pathologic and immunohistochemical analysis.
AB  - Pituitary tumor-transforming gene (PTTG) is also known to induce angiogenesis
      during pituitary tumorigenesis. It has not been clarified whether PTTG functions
      as a cytoplasmic or a nuclear protein. Pituitary tumor-transforming gene-1 is
      usually expressed in most pituitary tumors, and little is known about phosphatase
      and tensin homologue (PTEN). In our knowledge, it has not been studied in
      pituitary tumors. The aim of this study was to determine the correlation between
      proliferating cell nuclear antigen (PCNA) labeling index (LI), PTEN, and PTTG-1
      immunoexpression in pituitary adenomas. Forty-five pituitary adenomas were
      included-46.7% were males and 53.7% were females. The mean age was 43.18 +/- 9.42
      years (27-70 years). For functional pituitary adenoma (PA), it was 41.92 +/-
      6.63, and for nonfunctional pituitary adenomas, it was 44.62 +/- 11.85 (P =
      .003). Proliferating cell nuclear antigen LI range was 19.42 +/- 5.49; in
      functional pituitary adenomas, it was 41.92 +/- 6.63, and in nonfunctional
      adenomas, it was 44.62 +/- 11.85 (P = .081). The PTEN immunoreaction was positive
      weak in 21 (47%), moderate in 19 (42%), and strong in 5 (11%; P = .000). The PTTG
      1 gene was positive-weak in 18 (41%), moderate in 19 (41%), and strong in 6 (13%;
      P = .000). When we correlated PTEN + PCNA, it was P =.004, and PTEN + PTTG-1, it
      was P = .019. And when we correlated PCNA + PTGG-1, it was P = .262. In our
      results, we observed higher expression of PCNA-LI and PTTG-1 and loss of
      expression of PTEN. Nonfunctional hypophysis adenomas presented a higher PCNA,
      PTTG-1, and PTEN expression than functional ones. There was no difference between
      single-hormone-producing hypophysis adenomas or multiple-hormone-producing ones.
      Necrosis and hemorrhage were associated with PTEN expression, whereas atypias and
      mitosis figures were associated to PTTG-1 expression.

PMID- 18620996
TI  - HER-2 status in gastrointestinal stromal tumor.
AB  - Human epidermal growth factor receptor-2 (HER-2) encodes for the transmembrane
      glycoprotein HER-2 that is involved in activation of intracellular signal
      transduction pathways that control cell growth and differentiation. HER-2 is
      overexpressed in approximately 20% of patients with breast cancer and has been
      associated with poorer prognosis. Since 1998, the anti-HER-2 antibody trastuzumab
      has been used for the treatment of patients with HER-2-positive breast cancers.
      However, little information is available about the relationship between HER-2 and
      gastrointestinal stromal tumors. This study's purpose was to determine the HER-2
      status in gastrointestinal stromal tumors. We found that all 477 cases included
      in this study were negative (score 0) by immunohistochemistry using HercepTest,
      and no HER-2 gene amplification was detected in 71 cases submitted to
      fluorescence in situ hybridization. These results show that HER-2 may not have
      any role in gastrointestinal stromal tumor pathogenesis and that the neoplasm may
      not be suitable for treatment with trastuzumab.

PMID- 18620997
TI  - Cranial vault metastasis of giant cell tumor.
AB  - Giant cell tumors are benign bony tumors involving the epiphysis of long bones.
      Here, we present a case of giant cell tumor involving the parietal bone that had
      metastasized from the sacrum. A 36-year-old healthy woman presented to
      neurosurgery clinic in April 2005 reporting a "bump" over the left parietal area
      that had been increasing in size over the past 6 months. The lesion was
      nontender, and the patient had no other associated neurological symptoms. As we
      have presented here, cranial vault metastases can occur and should be considered
      in a differential diagnosis of bony lesions found in this location. These distant
      metastases, although relatively uncommon, must be managed aggressively. Newer
      radiation treatments seem to be a promising favorable adjunct to wide local
      resection and should be investigated further for these tumors.

PMID- 18620998
TI  - Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma.
AB  - A case showing the typical clinical and pathological features of splenic
      micronodular T-cell/histiocyte-rich large B-cell lymphoma is presented. Since the
      series recorded by Dogan et al (Am J Surg Pathol 2003;27:903-911), there have
      been very few reports on this lymphoma variant. Our case presents minor
      variations on the recorded features. Possible reasons for the scarcity of reports
      and for the confirmation of this lymphoma as a variant of T-cell-rich large B
      cell lymphoma are discussed.

PMID- 18620999
TI  - Angiomyolipoma of the anterior mediastinum.
AB  - Angiomyolipoma is a benign tumor composed of varying proportions of smooth muscle
      cells, blood vessels, and adipose tissue that most commonly occurs in the kidney.
      Sporadic lesions and lesions arising in the setting of the tuberous sclerosis
      complex have been reported in extrarenal sites. We present the case of an
      incidentally discovered angiomyolipoma in the anterior mediastinum. Thymoma was
      suspected clinically, and the lesion was composed mainly of spindled-to
      epithelioid cells arranged in a histologic pattern reminiscent of
      hemangiopericytoma, a pattern that has been described in thymoma.
      Immunohistochemical stains revealed positivity for smooth muscle actin and HMB
      45, revealing the expression of smooth muscle and melanocytic markers
      characteristic of angiomyolipoma and other lesions in the PEComa family.

PMID- 18621000
TI  - Cystic pancreatic schwannoma in a 46-year-old man.
AB  - Pancreatic schwannomas are a rare benign mesenchymal neoplasm of the pancreas.
      They are thought to arise from the epineurium of either autonomic sympathetic or
      parasympathetic fibers, which course through the pancreas with the vagus nerve.
      Large pancreatic schwannomas often undergo cystic change, which causes them to be
      often confused with other more common cystic pancreatic neoplasms preoperatively.
      The radiological, histologic, and immunohistochemical findings of pancreatic
      schwannomas are consistent with those of neoplasms found in other sites.
      Treatment is by surgical resection, and the prognosis is excellent. The awareness
      and, to some extent, knowledge of less common tumors in the pancreas are needed
      to achieve the diagnosis. We discuss the clinical and pathologic features and
      differential diagnosis of cystic pancreatic tumors.

PMID- 18621001
TI  - Primary pleomorphic rhabdomyosarcoma of the kidney in an adult.
AB  - Sarcoma of the kidney is uncommon and represents between 1% and 3% of all
      malignant renal tumors. Primary rhabdomyosarcoma of the kidney in adult age is
      unusual, and only sporadic cases have been reported. This is a very aggressive
      tumor with dismal prognosis. We report a new case of pleomorphic rhabdomyosarcoma
      of the kidney in an adult patient.

PMID- 18621002
TI  - Pathologists are from Mercury, clinicians are from Uranus: the perverted
      prospects for perceptual pathology.
AB  - Clinicians and pathologists do their work, of course, in quite different ways.
      Because both groups are trained as physicians, however, this training commonality
      makes all involved seem basically to be on the same "medical team." There are,
      nevertheless, some fundamental differences between the 2 groups that can on
      occasion cause significant difficulties in mutual understanding; there are
      reasons to believe that such differences are becoming more pronounced. Although
      the differences in viewpoints are often subtle and, therefore, seemingly not very
      important, these differences have very profound causes and can be profound in
      their effects. This narrative examines the underlying broad historical
      sociological-philosophical bases for these differences with the aim of
      illuminating their importance to medicine and their prospective importance to
      pathology in particular.

PMID- 18621003
TI  - PEPped up: induction of Candida albicans virulence by bacterial cell wall
      fragments.
AB  - In this issue, Xu et al. (2008) report that Candida albicans, a prevalent fungal
      pathogen, expresses virulence-related attributes in response to bacterial
      peptidoglycan components, muramyl dipeptides, in human serum. Conserved elements
      in human and fungal detection of muramyl dipeptides highlight a common ability to
      perceive proximal bacterial populations.

PMID- 18621004
TI  - HIV and chemokine binding to red blood cells--DARC matters.
AB  - A mutation in the Duffy antigen (DARC) that abrogates receptor expression and
      gives profound protection against some malaria species has become almost
      universal in African populations. He et al. (2008) show that this polymorphism
      also leads to significantly increased susceptibility to HIV-1 infection but,
      paradoxically, to prolonged survival in HIV-1-infected subjects.

PMID- 18621005
TI  - Stabbing in the BAK--an original target for avirulence genes of plant pathogens.
AB  - Paradoxically, plant pathogens possess avirulence genes that render them
      avirulent in resistant hosts. In Cell Host & Microbe, Shan et al. (2008) show
      that the original role of the Pseudomonas syringae avirulence genes AvrPto and
      AvrPtoB is to target BAK1, a protein kinase important in hormone and innate
      immunity signaling.

PMID- 18621006
TI  - The Yeast Saccharomyces cerevisiae: a versatile model system for the
      identification and characterization of bacterial virulence proteins.
AB  - Microbial pathogens utilize complex secretion systems to deliver proteins into
      host cells. These effector proteins target and usurp host cell processes to
      promote infection and cause disease. While secretion systems are conserved, each
      pathogen delivers its own unique set of effectors. The identification and
      characterization of these effector proteins has been difficult, often limited by
      the lack of detectable signal sequences and functional redundancy. Model systems
      including yeast, worms, flies, and fish are being used to circumvent these
      issues. This technical review details the versatility and utility of yeast
      Saccharomyces cerevisiae as a system to identify and characterize bacterial
      effectors.

PMID- 18621007
TI  - Bacterial effectors target the common signaling partner BAK1 to disrupt multiple
      MAMP receptor-signaling complexes and impede plant immunity.
AB  - Successful pathogens have evolved strategies to interfere with host immune
      systems. For example, the ubiquitous plant pathogen Pseudomonas syringae injects
      two sequence-distinct effectors, AvrPto and AvrPtoB, to intercept convergent
      innate immune responses stimulated by multiple microbe-associated molecular
      patterns (MAMPs). However, the direct host targets and precise molecular
      mechanisms of bacterial effectors remain largely obscure. We show that AvrPto and
      AvrPtoB bind the Arabidopsis receptor-like kinase BAK1, a shared signaling
      partner of both the flagellin receptor FLS2 and the brassinosteroid receptor
      BRI1. This targeting interferes with ligand-dependent association of FLS2 with
      BAK1 during infection. It also impedes BAK1-dependent host immune responses to
      diverse other MAMPs and brassinosteroid signaling. Significantly, the structural
      basis of AvrPto-BAK1 interaction appears to be distinct from AvrPto-Pto
      association required for effector-triggered immunity. These findings uncover a
      unique strategy of bacterial pathogenesis where virulence effectors block signal
      transmission through a key common component of multiple MAMP-receptor complexes.

PMID- 18621008
TI  - Bacterial peptidoglycan triggers Candida albicans hyphal growth by directly
      activating the adenylyl cyclase Cyr1p.
AB  - Human serum potently induces hyphal development of the polymorphic fungal
      pathogen Candida albicans, a phenotype that contributes critically to infections.
      The fungal adenylyl cyclase Cyr1p is a key component of the cAMP/PKA-signaling
      pathway that controls diverse infection-related traits, including hyphal
      morphogenesis. However, identity of the serum hyphal inducer(s) and its fungal
      sensor remain unknown. Our initial analyses of active serum fractions revealed
      signs of bacterial peptidoglycan (PGN)-like molecules. Here, we show that several
      purified and synthetic muramyl dipeptides (MDPs), subunits of PGN, can strongly
      promote C. albicans hyphal growth. Analogous to PGN recognition by the mammalian
      sensors Nod1 and Nod2 through their leucine-rich-repeat (LRR) domain, we show
      that MDPs activate Cyr1p by directly binding to its LRR domain. Given the
      abundance of PGN in the intestine, a natural habitat and invasion site for C.
      albicans, our findings have important implications for the mechanisms of
      infection by this pathogen.

PMID- 18621009
TI  - Erythrocyte binding protein PfRH5 polymorphisms determine species-specific
      pathways of Plasmodium falciparum invasion.
AB  - Some human malaria Plasmodium falciparum parasites, but not others, also cause
      disease in Aotus monkeys. To identify the basis for this variation, we crossed
      two clones that differ in Aotus nancymaae virulence and mapped inherited traits
      of infectivity to erythrocyte invasion by linkage analysis. A major pathway of
      invasion was linked to polymorphisms in a putative erythrocyte binding protein,
      PfRH5, found in the apical region of merozoites. Polymorphisms of PfRH5 from the
      A. nancymaae-virulent parent transformed the nonvirulent parent to a virulent
      parasite. Conversely, replacements that removed these polymorphisms from PfRH5
      converted a virulent progeny clone to a nonvirulent parasite. Further, a
      proteolytic fragment of PfRH5 from the infective parasites bound to A. nancymaae
      erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human
      infection, and that amino acid substitutions can cause its binding domain to
      recognize different human erythrocyte surface receptors.

PMID- 18621010
TI  - Duffy antigen receptor for chemokines mediates trans-infection of HIV-1 from red
      blood cells to target cells and affects HIV-AIDS susceptibility.
AB  - Duffy antigen receptor for chemokines (DARC) expressed on red blood cells (RBCs)
      influences plasma levels of HIV-1-suppressive and proinflammatory chemokines such
      as CCL5/RANTES. DARC is also the RBC receptor for Plasmodium vivax. Africans with
      DARC -46C/C genotype, which confers a DARC-negative phenotype, are resistant to
      vivax malaria. Here, we show that HIV-1 attaches to RBCs via DARC, effecting
      trans-infection of target cells. In African Americans, DARC -46C/C is associated
      with 40% increase in the odds of acquiring HIV-1. If extrapolated to Africans,
      approximately 11% of the HIV-1 burden in Africa may be linked to this genotype.
      After infection occurs, however, DARC-negative RBC status is associated with
      slower disease progression. Furthermore, the disease-accelerating effect of a
      previously described CCL5 polymorphism is evident only in DARC-expressing and not
      in DARC-negative HIV-infected individuals. Thus, DARC influences HIV/AIDS
      susceptibility by mediating trans-infection of HIV-1 and by affecting both
      chemokine-HIV interactions and chemokine-driven inflammation.

PMID- 18621011
TI  - Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction
      in HIV/AIDS.
AB  - B lymphocyte hyperactivation and elevated immunoglobulin levels
      (hypergammaglobulinemia) are pathogenic manifestations of HIV-1 infection. Here
      we provide evidence that these hallmarks are caused by a soluble factor whose
      production by infected macrophages is induced by the HIV-1 Nef protein. In vitro,
      HIV-1-infected macrophages or macrophages expressing Nef promoted B cell
      activation and differentiation to immunoglobulin-secreting cells. Nef-mediated
      activation of NF-kappaB in macrophages induced secretion of the acute-phase
      protein ferritin, and ferritin was necessary and sufficient for the observed Nef
      dependent B cell changes. The extent of hypergammaglobulinemia in HIV-1-infected
      individuals correlated directly with plasma ferritin levels and with viral load.
      Furthermore, the induction of ferritin production and hypergammaglobulinemia was
      recapitulated when Nef was specifically expressed in macrophages and T cells of
      transgenic mice. Collectively, these results indicate that the HIV-1 Nef protein
      carries a pathogenic determinant that governs B cell defects in HIV-1 infection.

PMID- 18621012
TI  - Position-dependent function for a tandem microRNA miR-122-binding site located in
      the hepatitis C virus RNA genome.
AB  - MicroRNAs usually interact with 3' noncoding regions (3'NCRs) of target mRNAs
      leading to downregulation of mRNA expression. In contrast, liver-specific
      microRNA miR-122 interacts with the 5' end of the hepatitis C virus RNA genome,
      resulting in increased viral RNA abundance. We find that inserting the viral miR
      122 binding site into the 3' noncoding region of a reporter mRNA leads to
      downregulation of mRNA expression, indicating that the location of the miR-122
      binding site dictates its effect on gene regulation. Furthermore, we discovered
      an adjacent, second miR-122 binding site, separated from the first by a highly
      conserved 14-nucleotide sequence. Mutational analysis demonstrates that both miR
      122 binding sites in a single viral genome are occupied by the microRNA and
      function cooperatively to regulate target gene expression. These findings set a
      paradigm for dual, position-dependent functions of tandem microRNA-binding sites.
      Targeting an oligomeric microRNA complex offers potential as an antiviral
      intervention strategy.

PMID- 18621013
TI  - The epinephrine assay for superoxide: why dopamine does not work.
AB  - Superoxide oxidizes epinephrine to a semiquinone, initiating a series of
      reactions leading to the colored product adrenochrome. This popular assay for
      superoxide is more sensitive at higher pH, and it does not work if dopamine is
      used instead of epinephrine. A kinetic analysis shows that these effects can be
      explained by competing reactions that lower the yield of the observed product.
      The catecholamine quinone may cyclize to form the absorbing product, or it may be
      reduced back to the semiquinone by superoxide. For epinephrine, the quinone
      cyclizes quickly and adrenochrome formation dominates, but for dopamine, the
      quinone cyclizes slowly and the back reaction prevails. The yield of adrenochrome
      increases if the epinephrine semiquinone reacts with O(2) to form more
      superoxide, but this reaction competes with disproportionation of the
      semiquinone. Because disproportionation slows as pH increases, both superoxide
      formation and the yield of adrenochrome increase at higher pH.

PMID- 18621014
TI  - Calcium-activated membrane interaction of the islet amyloid polypeptide:
      implications in the pathogenesis of type II diabetes mellitus.
AB  - The role played by Ca(2+) ions in the interaction of the human islet amyloid
      polypeptide (hIAPP) with model membranes has been investigated by differential
      scanning calorimetry (DSC) and circular dichroism (CD) experiments. In
      particular, the interaction of hIAPP and its rat isoform (rIAPP) with
      zwitterionic dipalmitoyl-phosphatidylcholine (DPPC), negatively charged
      dipalmitoyl-phosphatidylserine (DPPS) vesicles and with a 3:1 mixtures of them,
      has been studied in the presence of Ca(2+) ions. The experiments have evidenced
      that amorphous, soluble hIAPP assemblies interact with the hydrophobic core of
      DPPC bilayers. Conversely, the presence of Ca(2+) ions is necessary to activate a
      preferential interaction of hIAPP with the hydrophobic core of DPPS membranes.
      These findings support the hypothesis that an impaired cellular homeostasis of
      Ca(2+) ions may promote the insertion of hIAPP into the hydrophobic core of
      carrier vesicles which is thought to contribute to an eventual intracellular
      accumulation of beta-sheet rich hIAPP aggregates.

PMID- 18621015
TI  - Mangiferin inhibits cyclooxygenase-2 expression and prostaglandin E2 production
      in activated rat microglial cells.
AB  - Mangiferin, a naturally occurring glucosylxanthone, has potent antioxidant and
      anti-inflammatory properties, as demonstrated in several reports. However, very
      limited information is available on the effects of this natural polyphenol on
      microglial activation. Thus, the aim of this study was to examine whether
      mangiferin is able to reduce prostaglandin E(2) (PGE(2)) and 8-iso-prostaglandin
      F(2alpha) (8-iso-PGF(2alpha)) production by lipopolysaccharide (LPS)-activated
      primary rat microglia. Microglial cells were stimulated with 10ng/ml of LPS in
      the presence or absence of different concentrations of mangiferin (1-50 microM).
      After 24h incubation, culture media were collected to measure the production of
      PGE(2) and 8-iso-PGF(2alpha) using enzyme immunoassays. Protein levels of
      cyclooxygenase (COX)-1 and COX-2 were studied by immunoblotting after 24h of
      incubation with LPS. Mangiferin potently reduced LPS-induced PGE(2) synthesis and
      the formation of 8-iso-PGF(2alpha). Interestingly, mangiferin dose-dependently
      reduced LPS-induced COX-2 protein synthesis without modifying COX-2
      transcription. This was due to a decrease in COX-2 transcript stability. However,
      mangiferin did not modify LPS-mediated phosphorylation of p38 mitogen-activated
      protein kinase (p38 MAPK), a key factor involved in enhancing COX-2 mRNA
      stability and COX-2 translation in primary microglia. Mangiferin had no effects
      on LPS-induced expression of inducible nitric oxide synthase (iNOS) or TNF-alpha
      production. Taken together, results from the present study indicate that
      mangiferin is able to limit microglial activation, in terms of attenuation of
      PGE(2) production, free radical formation and reduction in COX-2 synthesis
      induced by LPS. These data suggest that modulation of microglial activation might
      contribute to the mechanism of cerebral protection by mangiferin.

PMID- 18621016
TI  - Specificity of the N-benzoyl transferase responsible for the last step of Taxol
      biosynthesis.
AB  - The last few steps in the biosynthesis of the anticancer drug Taxol in yew
      (Taxus) species are thought to involve the attachment of beta-phenylalanine to
      the C13-O-position of the advanced taxane diterpenoid intermediate baccatin III
      to yield N-debenzoyl-2'-deoxytaxol, followed by hydroxylation on the side chain
      at the C2'-position to afford N-debenzoyltaxol, and finally N-benzoylation to
      complete the pathway. A cDNA encoding the N-benzoyl transferase that catalyzes
      the terminal step of the reaction sequence was previously isolated from a family
      of transferase clones (derived from an induced Taxus cell cDNA library) by
      functional characterization of the corresponding recombinant enzyme using the
      available surrogate substrate N-debenzoyl-2'-deoxytaxol [K. Walker, R. Long, R.
      Croteau, Proc. Nat. Acad. Sci. USA 99 (2002) 9166-9171]. Semi-synthetic N
      debenzoyltaxol was prepared by coupling of 7-triethylsilybaccatin III and (2R,3S)
      beta-phenylisoserine protected as the N-Boc N,O-isopropylidene derivative by
      means of carbodiimide activation and formic acid deprotections. The selectivity
      of the recombinant N-transferase for N-debenzoyltaxol was evaluated, and the
      enzyme was shown to prefer, by a catalytic efficiency factor of two, N
      debenzoyltaxol over N-debenzoyl-2'-deoxytaxol as the taxoid co-substrate in the
      benzoyl transfer reaction, consistent with the assembly sequence involving 2'
      hydroxylation prior to N-benzoylation. Selectivity for the acyl/aroyl-CoA co
      substrate was also examined, and the enzyme was shown to prefer benzoyl-CoA.
      Transfer from tigloyl-CoA to N-debenzoyltaxol to afford cephalomannine (Taxol B)
      was not observed, nor was transfer observed from hexanoyl-CoA or butanoyl-CoA to
      yield Taxol C or Taxol D, respectively. These results support the proposed
      sequence of reactions for C13-O-side chain assembly in Taxol biosynthesis, and
      suggest that other N-transferases are responsible for the formation of related,
      late pathway, N-acylated taxoids.

PMID- 18621017
TI  - Detoxification of promutagenic aldehydes derived from methylpyrenes by human
      aldehyde dehydrogenases ALDH2 and ALDH3A1.
AB  - Methylated polycyclic aromatic hydrocarbons can be metabolically activated via
      benzylic hydroxylation and sulpho conjugation to reactive esters, which can
      induce mutations and tumours. Yet, further oxidation of the alcohol may compete
      with this toxification. We previously demonstrated that several human alcohol
      dehydrogenases (ADH1C, 2, 3 and 4) oxidise various benzylic alcohols (derived
      from alkylated pyrenes) to their aldehydes with high catalytic efficiency.
      However, all these ADHs also catalysed the reverse reaction, the reduction of the
      aldehydes to the alcohols, with comparable or higher efficiency. Thus, final
      detoxification requires elimination of the aldehydes by further
      biotransformation. We have expressed two human aldehyde dehydrogenases (ALDH2 and
      3A1) in bacteria. All pyrene aldehydes studied (1-, 2- and 4-formylpyrene, 1
      formyl-6-methylpyrene and 1-formyl-8-methylpyrene) were high-affinity substrates
      for ALDH2 (K(m)=0.027-0.9 microM) as well as ALDH3A1 (K(m)=0.78-11 microM).
      Catalytic efficiencies (k(cat)/K(m)) were higher for ALDH2 than ALDH3A1 by a
      moderate to a very large margin depending on the substrate. Most important, they
      were also substantially higher than the catalytic efficiencies of the various
      ADHs for the reduction the aldehydes to the alcohols. These kinetic properties
      ensure that ALDHs, and particularly ALDH2, can complete the ADH-mediated
      detoxification.

PMID- 18621018
TI  - Oxidative stress causes membrane phospholipid rearrangement and shedding from RBC
      membranes--an NMR study.
AB  - Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the
      relationship between oxidative stress experienced by RBCs and their phospholipid
      content and shedding. Using 1H-NMR, we demonstrated a higher lactate/pyruvate
      ratio, an indicator of oxidative stress, in normal RBCs treated with oxidants (t
      butylhydroxyperoxide and H2O2) as well as in beta-thalassemic RBCs. Using 31P
      NMR, we found 30% more phosphatidylcholine (PC), and unexpectedly, 35% less
      phosphatidylserine (PS) in the thalassemic RBCs. PS was decreased by treatment
      with oxidants and increased by anti-oxidants (vitamin C and N-acetyl cysteine);
      PC showed the opposite behavior. Thalassemic RBCs incubated in phosphate buffered
      saline produced more PS in the supernatant than normal RBCs. Anti-oxidants
      reduced the PS in the supernatant while oxidants increased it. Plasma of
      thalassemic patients contained 2.6-fold and 1.8-fold more PS and PC,
      respectively, than normal plasma. These results indicate that the decreased PS in
      RBCs resulted from increased shedding. The nature of the shed PS was studied by
      purifying and analyzing membranous microparticles from the plasma and RBC
      supernatants. More PS was found in microparticles purified from thalassemic
      plasma and RBC supernatants (5.6- and 4.8-fold, respectively) than in their
      normal counterparts. However, the bulk (80-90%) of the shed PS was not associated
      with microparticles. The significance of PS shedding for RBC survival needs
      further clarification.

PMID- 18621019
TI  - A novel agonist effect on the nicotinic acetylcholine receptor exerted by the
      anticonvulsive drug Lamotrigine.
AB  - The anticonvulsive drug Lamotrigine (LTG) is found to activate adult muscle
      nicotinic acetylcholine receptors (AChR). Single-channel patch-clamp recordings
      showed that LTG (0.05-400 microM) applied alone is able to open AChR channels.
      [125I]alpha-bungarotoxin-binding studies further indicate that LTG does not bind
      to the canonical ACh-binding sites. Fluorescence experiments using the probe
      crystal violet demonstrate that LTG induces the transition from the resting state
      to the desensitized state of the AChR in the presence of excess alpha
      bungarotoxin, that is, when the agonist site is blocked. Allosterically
      potentiating ligands or the open-channel blocker QX-314 exhibited a behavior
      different from that of LTG. We conclude that LTG activates the AChR through a
      site that is different from those of full agonists/competitive antagonists and
      allosterically-potentiating ligands, respectively.

PMID- 18621020
TI  - Multidrug resistance-associated protein 1 as a major mediator of basal and
      apoptotic glutathione release.
AB  - The proteins responsible for reduced glutathione (GSH) export under both basal
      conditions and in cells undergoing apoptosis have not yet been identified,
      although recent studies implicate some members of the multidrug resistance
      associated protein family (MRP/ABCC) in this process. To examine the role of MRP1
      in GSH release, the present study measured basal and apoptotic GSH efflux in
      HEK293 cells stably transfected with human MRP1. MRP1-overexpressing cells had
      lower intracellular GSH levels and higher levels of GSH release, under both basal
      conditions and after apoptosis was induced with either Fas antibody or
      staurosporine. Despite the enhanced GSH efflux in MRP1-overexpressing cells,
      intracellular GSH levels were not further depleted when cells were treated with
      Fas antibody or staurosporine, suggesting an increase in GSH synthesis. MRP1
      overexpressing cells were also less susceptible to apoptosis, suggesting that the
      stable intracellular GSH levels may have protected cells from death. Overall,
      these results demonstrate that basal and apoptotic GSH release are markedly
      enhanced in cells overexpressing MRP1, suggesting that MRP1 plays a key role in
      these processes. The enhanced GSH release, with a concurrent decrease of
      intracellular GSH, appears to be necessary for the progression of apoptosis.

PMID- 18621021
TI  - Quantitative multiplexed quantum dot immunohistochemistry.
AB  - Quantum dots are photostable fluorescent semiconductor nanocrystals possessing
      wide excitation and bright narrow, symmetrical, emission spectra. These
      characteristics have engendered considerable interest in their application in
      multiplex immunohistochemistry for biomarker quantification and co-localisation
      in clinical samples. Robust quantitation allows biomarker validation, and there
      is growing need for multiplex staining due to limited quantity of clinical
      samples. Most reported multiplexed quantum dot staining used sequential methods
      that are laborious and impractical in a high-throughput setting. Problems
      associated with sequential multiplex staining have been investigated and a method
      developed using QDs conjugated to biotinylated primary antibodies, enabling
      simultaneous multiplex staining with three antibodies. CD34, Cytokeratin 18 and
      cleaved Caspase 3 were triplexed in tonsillar tissue using an 8h protocol, each
      localised to separate cellular compartments. This demonstrates utility of the
      method for biomarker measurement enabling rapid measurement of multiple co
      localised biomarkers on single paraffin tissue sections, of importance for
      clinical trial studies.

PMID- 18621023
TI  - Development of SM5-1-conjugated ultrasmall superparamagnetic iron oxide
      nanoparticles for hepatoma detection.
AB  - Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are maghemite or
      magnetite nanoparticles currently used as contrast agent in magnetic resonance
      imaging (MRI). In this study, a targeted contrast agent (SM-USPIO) was prepared
      by conjugating coprecipitated USPIO to a humanized SM5-1 antibody which can
      specifically react with human hepatocellular carcinoma (HCC) cells. The binding
      and internalization of SM-USPIO to the HCC cell line ch-hep-3 was confirmed by
      flow cytometry and confocal microscopy. Furthermore, SM-USPIO was demonstrated to
      be able to selectively accumulate in the tumor cells, resulting in a marked
      decrease of MRI T2-weighted signal intensity. Biodistribution studies
      demonstrated the efficient accumulation of SM-USPIO in the ch-hep-3 tumor in nude
      mice. The in vivo study in the ch-hep-3 tumor-bearing nude mice indicated that
      MRI using the SM-USPIO as contrast agent possessed good diagnostic ability,
      suggesting that SM-USPIO had the potential to be a promising targeted contrast
      agent for diagnosis of HCC.

PMID- 18621022
TI  - HaloTag protein-mediated specific labeling of living cells with quantum dots.
AB  - Quantum dots emerge as an attractive alternative to small molecule fluorophores
      as fluorescent tags for in vivo cell labeling and imaging. This communication
      presents a method for specific labeling of live cells using quantum dots. The
      labeling is mediated by HaloTag protein expressed at the cell surface which forms
      a stable covalent adduct with its ligand (HaloTag ligand). The labeling can be
      performed in one single step with quantum dot conjugates that are functionalized
      with HaloTag ligand, or in two steps with biotinylated HaloTag ligand first and
      followed by streptavidin coated quantum dots. Live cell fluorescence imaging
      indicates that the labeling is specific and takes place at the cell surface. This
      HaloTag protein-mediated cell labeling method should facilitate the application
      of quantum dots for live cell imaging.

PMID- 18621024
TI  - Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF
      kappaB.
AB  - Nucleoporin 88 kDa (Nup88) is a tumor marker, overexpressed in various types of
      cancer. In Drosophila Nup88 (mbo) was reported to selectively mediate the
      nucleocytoplasmic transport of NF-kappaB, an ubiquitous transcription factor
      involved in immune responses, apoptosis, and cancer. We addressed the function of
      Nup88 in mammalian cells. Selective depletion of Nup88 by small interfering RNA
      (siRNA) inhibited NF-kappaB-dependent reporter gene activation and the nuclear
      translocation of NF-kappaB without affecting the upstream activation pathway in
      NIH3T3 cells. In contrast, nuclear translocation of glucocorticoid receptor was
      not reduced by the depletion of Nup88. In metastatic melanoma cells
      overexpressing Nup88, constitutive activation of NF-kappaB was found both in
      nucleus and cytoplasm. Nup88 depletion in these cells reduced TNF-induced nuclear
      accumulation of NF-kappaB subunits. We conclude that Nup88 regulates the activity
      of NF-kappaB at the level of nucleocytoplasmic transport. Overexpression of Nup88
      in tumor cells may, thus be involved in the constitutive NF-kappaB activation.

PMID- 18621025
TI  - Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal
      tumor.
AB  - Angiogenesis plays a key role in the development of a wide variety of malignant
      tumors. The approach of targeting antiangiogenesis has become an important field
      of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the
      kringle 5 of human plasminogen) has been mutated by changing leucine71 to
      arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus
      expressing mK5, was constructed. It showed stronger inhibition on proliferation
      of human umbilical vein endothelial cell. Moreover, in tube formation and
      embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective
      antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious
      suppression on the growth of colorectal tumor xenografts and prolonged the life
      span of nude mice. These results indicate that ZD55-mK5 is a potent agent for
      inhibiting the tumor angiogenesis and tumor growth.

PMID- 18621026
TI  - A fatty acid elongase ELO with novel activity from Dictyostelium discoideum.
AB  - Fatty acid elongation was examined in the cellular slime mold, Dictyostelium
      discoideum. Profiling of the total fatty acid content of D. discoideum indicated
      that fatty acid elongation is active. Orthologs of the fatty acid elongase ELO
      family were identified in the D. discoideum genome and the cDNA for one, eloA,
      was cloned and functionally characterized by expression in yeast. EloA is a
      highly active ELO with strict substrate specificity for monounsaturated fatty
      acids, in particular 16:1(Delta9) to produce the unusual 18:1(Delta11) fatty
      acid. This is the first report on fatty acid elongation in a cellular slime mold.

PMID- 18621028
TI  - Molecular regulation of antioxidant ability in the hippocampus of EL mice.
AB  - We recently found that the antioxidant ability was remarkably decreased in the
      hippocampus (Hipp) of EL at 8 weeks of age utilizing ESR spectroscopy. In this
      study, in addition to evaluating the extracellular glutamate concentration, we
      tried to determine whether or not changes in the expression of cystine/glutamate
      exchanger (xCT) and glutamate transporter take place in the Hipp of EL. EL mice
      and DDY mice at 5, 10, and 20 weeks of age were used for Exp. I and II,
      respectively. Exp. I: During the interictal state, dialysate was collected from
      the ventral Hipp using a microdialysis technique, and an extracellular
      concentration of glutamate ([Glu](o)) was measured with HPLC-ECD. Exp. II: The
      hippocampal expression of the glutamate transporter and xCT was estimated by
      Western blots. Exp. I: The level of [Glu](o) at 10 weeks of age was remarkably
      higher at other ages of EL mice, while [Glu](o) of DDY was unchanged as a result
      of age. Exp. II: The excitatory amino acid carrier-1 (EAAC-1) and xCT of EL mice
      at 10 weeks of age decreased more than those of DDY. GLAST and GLT-1 of EL mice
      at 5 weeks of age decreased more than those of DDY at the same age. No
      differences were found between EL and DDY for GLAST and GLT-1 at other ages.
      According to previous studies, the decreased endogenous antioxidant potential
      observed at 10 weeks of age is a very likely explanation for ictogenesis. The
      decreased xCT expression at 10 weeks of age could provide the molecular mechanism
      to explain the depletion of the endogenous antioxidant ability of EL mice during
      ictogenesis. In addition to the depletion of antioxidant ability, decreased EAAC
      1 at this period could be one reason for the collapse of the molecular action of
      inhibition. These molecular findings support the idea that the elevation of
      [Glu](o) at 10 weeks of age triggers ictogenesis.

PMID- 18621027
TI  - The dependence of P300 amplitude on gamma synchrony breaks down in schizophrenia.
AB  - INTRODUCTION: Auditory P300 amplitude reduction in schizophrenia is canonical and
      may be explained by poor synchronization or reduced power of the underlying
      neural activity. We asked if patients have reduced synchrony and power, and
      whether together with P300 amplitude, they make unique or overlapping
      contributions to the discrimination between patients and controls. We also asked
      whether people who have large P300s have higher power and greater synchrony of
      neural activity, and if the relationships between P300 and power and synchrony
      are different in patients and healthy controls. METHODS: We recorded EEG data
      from 22 controls and 21 patients with schizophrenia (DSM-IV) while they performed
      an auditory target detection task. We used wavelet analyses of the single trial
      data to estimate total power and synchrony of delta, theta, alpha, beta, and
      gamma activity in a 50ms window around the peak of the P300 to the target. We
      measured P300 amplitude from the average of the single trials, in a 50ms window
      around its peak. RESULTS AND CONCLUSIONS: P300 amplitude and delta and theta
      synchrony were reduced in patients; delta power and synchrony better
      distinguished between groups than P300 amplitude. In healthy controls, but not
      patients, gamma synchrony predicted P300 amplitude. In patients, P300 and gamma
      synchrony are affected by independent factors; the relationship between them is
      attenuated by an additional pathophysiological process.

PMID- 18621029
TI  - Melatonin signaling in mouse cerebellar granule cells with variable native MT1
      and MT2 melatonin receptors.
AB  - Although G protein-coupled MT1 and MT2 melatonin receptors are expressed in
      neurons of the mammalian brain including in humans, relatively little is known
      about the influence of native MT1 and MT2 melatonin receptors on neuronal
      melatonin signaling. Whereas human cerebellar granule cells (CGC) express only
      MT1 receptors, mouse CGC express both MT1 and MT2. To study the effects of
      altered neuronal MT1/MT2 receptors, we used CGC cultures prepared from immature
      cerebella of wild-type mice (MT1/MT2 CGC) and MT1- and MT2-knockout mice (MT2 and
      MT1 CGC, respectively). Here we report that in MT1/MT2 cultures, physiological
      (low nanomolar) concentrations of melatonin decrease the activity
      (phosphorylation) of extracellular-signal-regulated kinase (ERK) whereas a
      micromolar concentration was ineffective. Both MT1 and MT2 deficiencies
      transformed the melatonin inhibition of ERK into melatonin-induced ERK
      activation. In MT1/MT2 CGC, 1 nM melatonin inhibited serine/threonine kinase Akt,
      whereas in MT1 and MT2 CGC, this concentration was ineffective. Under these
      conditions, both MT1 and MT2 deficiencies prevented melatonin from inhibiting
      forskolin-stimulated cAMP levels and cFos immunoreactivity. We demonstrated that
      selective removal of native neuronal MT1 and MT2 receptors has a profound effect
      on the intracellular actions of low/physiological concentrations of melatonin.
      Since the expression of MT1 and MT2 receptors is cell-type-specific and species
      dependent, we postulate that the pattern of expression of neuronal melatonin
      receptor types in different brain areas and cells could determine the
      capabilities of endogenous melatonin in regulating neuronal functioning.

PMID- 18621030
TI  - N-acetylaspartate synthesis in the brain: mitochondria vs. microsomes.
AB  - Several reports during the last three decades have indicated that biosynthesis of
      N-acetylaspartate (NAA) occurs primarily in the mitochondria. But a recent report
      by Lu et al. in this journal [2004; 122: 71-78] and subsequent two reports that
      cited those data suggested a predominant microsomal localization of the NAA
      biosynthetic enzyme, which is surprising in view of what is known about the
      biological functions of NAA. Therefore we reinvestigated this issue in rat brain
      homogenates using a similar fractionation procedure used by Lu et al. but without
      the loss of enzyme activity that they have encountered. We found that about 70%
      of the total Asp-NAT activity in the crude supernatant was present in the
      mitochondrial fraction which is about 5 times more than that in the microsomes.
      We found similar results in the case of the enzyme from bovine brain. In
      subsequent studies, we also have found that Asp-NAT activity in the bovine brain
      is very similar to that in the rat brain in substrate specificity and
      chromatographic characteristics including the high molecular weight pattern
      (approx. 670 kD) on size-exclusion HPLC.

PMID- 18621031
TI  - The phosphatidylinositol 3-kinase inhibitor LY 294002 inhibits GlyT1-mediated
      glycine uptake.
AB  - The actions of neurotransmitter glycine are regulated by the Na+/Cl(-) dependent
      high-affinity glycine transporters, GlyT1 and GlyT2. These two members of the
      SLC6 transport family have been cloned and extensively characterized, however
      relatively little is known regarding their modulation. In the present study,
      glycine uptake in primary cultures of rat embryonic cortex has been characterized
      and the effects of the phosphatidylinositol 3 (PI3) kinase inhibitors LY 294002
      and wortmannin on GlyT1- and GlyT2-mediated glycine uptake were investigated.
      GlyT1 inhibitors ALX 5407 and sarcosine reduced total glycine uptake to 80%
      whereas the specific GlyT2 inhibitor Org 25543 had no effect. In the presence of
      alanine, glycine uptake was completely blocked by the GlyT1 inhibitors ALX 5407
      and sarcosine, suggesting that the high-affinity glycine uptake occurs
      predominantly via GlyT1. Kinetic analysis of GlyT1 revealed the Km value of 27+/
      1.5 microM and Vmax value of 157+/-14 pmol/mg/min. LY 294002, a PI3 kinase
      inhibitor, blocked the GlyT1-mediated glycine uptake with an IC50 value of 81+/-2
      microM, whereas another inhibitor wortmannin did not show any effect. In human
      placental choriocarcinoma (JAR) cells, which have been previously shown to
      predominantly express GlyT1a, LY 294002 showed a similar potency with an IC50
      value of 86+/-3 microM. Immunoblots demonstrated that LY 294002 and wortmannin
      inhibited PI3 kinase-dependent Akt phosphorylation in the primary cultures with
      IC50 values of 10+/-4 microM and 7+/-1 nM, respectively. These results suggest
      that the commonly used PI3 kinase blocker LY 294002 may modulate GlyT1 function
      independent of PI3 kinase inhibition. Kinetic analysis in the presence of LY
      294002 demonstrated significant decreases of both Km and Vmax values, suggesting
      a mechanism of uncompetitive inhibition on GlyT1-mediated glycine uptake. In
      addition, glycine release was blocked by LY 294002. These results raised a
      possibility that LY 294002 might interact with GlyT1.

PMID- 18621032
TI  - The effect of varying talker identity and listening conditions on gaze behavior
      during audiovisual speech perception.
AB  - During face-to-face conversation the face provides auditory and visual linguistic
      information, and also conveys information about the identity of the speaker. This
      study investigated behavioral strategies involved in gathering visual information
      while watching talking faces. The effects of varying talker identity and varying
      the intelligibility of speech (by adding acoustic noise) on gaze behavior were
      measured with an eyetracker. Varying the intelligibility of the speech by adding
      noise had a noticeable effect on the location and duration of fixations. When
      noise was present subjects adopted a vantage point that was more centralized on
      the face by reducing the frequency of the fixations on the eyes and mouth and
      lengthening the duration of their gaze fixations on the nose and mouth. Varying
      talker identity resulted in a more modest change in gaze behavior that was
      modulated by the intelligibility of the speech. Although subjects generally used
      similar strategies to extract visual information in both talker variability
      conditions, when noise was absent there were more fixations on the mouth when
      viewing a different talker every trial as opposed to the same talker every trial.
      These findings provide a useful baseline for studies examining gaze behavior
      during audiovisual speech perception and perception of dynamic faces.

PMID- 18621033
TI  - Neural substrates for visual pattern recognition learning in Igo.
AB  - Different contexts require different visual pattern recognitions even for
      identical retinal inputs, and acquiring expertise in various visual-cognitive
      skills requires long-term training to become capable of recognizing relevant
      visual patterns in otherwise ambiguous stimuli. This 3-Tesla fMRI experiment
      exploited shikatsu-mondai (life-or-death problems) in the Oriental board game of
      Igo (Go) to identify the neural substrates supporting this gradual and adaptive
      learning. In shikatsu-mondai, the player adds stones to the board with the
      objective of making, or preventing the opponent from making nigan (two eyes), or
      the topology of figure of eight, with these stones. Without learning the game,
      passive viewing of shikatsu-mondai activated the occipito-temporal cortices,
      reflecting visual processing without the recognition of nigan. Several days after
      two-hour training, passive viewing of the same stimuli additionally activated the
      premotor area, intraparietal sulcus, and a visual area near the junction of the
      (left) intraparietal and transverse occipital sulci, demonstrating plastic
      changes in neuronal responsivity to the stimuli that contained indications of
      nigan. Behavioral tests confirmed that the participants had successfully learned
      to recognize nigan and solve the problems. In the newly activated regions, the
      level of neural activity while viewing the problems correlated positively with
      the level of achievement in learning. These results conformed to the hypothesis
      that recognition of a newly learned visual pattern is supported by the activities
      of fronto-parietal and visual cortical neurons that interact via newly formed
      functional connections among these regions. These connections would provide the
      medium by which the fronto-parietal system modulates visual cortical activity to
      attain behaviorally relevant perceptions.

PMID- 18621034
TI  - Progenitor cell-derived factors enhance photoreceptor survival in rat retinal
      explants.
AB  - Explantation of postnatal rat retinas is associated with degenerative events that
      show morphological similarities to human retinal degenerative disorders. The most
      evident morphological features are photoreceptor apoptosis involving caspase-3
      and Muller cell activation. The purpose of the present study was to determine the
      content of protective factors in rat retinal progenitor cells and analyze the
      influence of the identified factors on the survival of photoreceptor cells and
      retinal gliosis. Tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and
      vascular endothelial growth factor (VEGF) were identified as putative beneficial
      factors, and their combined effect was examined in rat retinal explant cultures.
      Photoreceptor apoptosis was estimated by cell counts of cleaved caspase-3 and
      caspase-12 immunolabeled as well as TUNEL labeled cells. TIMP-1 and VEGF in
      combination significantly suppressed photoreceptor apoptosis involving caspase-3
      activation. Cell counts of caspase-12 and TUNEL labeled photoreceptors showed no
      significant difference between the experiment and control retinas. TIMP-1 and
      VEGF appeared to have no effect on Muller cell activation as measured by GFAP and
      Ki-67 immunohistochemistry. Our data suggest that TIMP-1 and VEGF in combination
      promote the survival of photoreceptor cells in rat retinal explants, possibly by
      affecting a caspase-3 signaling pathway.

PMID- 18621035
TI  - Neuronal maturation-associated resistance of neurite degeneration caused by
      trophic factor deprivation or microtubule-disrupting agents.
AB  - Neurite (axon and dendrite) degeneration requires self-destructive programs
      independent of cell death programs to segregate neurite degeneration from cell
      soma demise. We have here addressed the question of whether neuritic degeneration
      is delayed or occurs normally under conditions in which sympathetic neurons
      acquire resistance to somal apoptosis upon maturation. For this purpose, we have
      examined both beading formation and fragmentation, two hall-marks of neurite
      degeneration, caused by three experimental paradigms including NGF deprivation,
      treatment with microtubule-disrupting agents, and in vitro Wallerian
      degeneration. Sympathetic neurons from 1-day-old mice or newborn rats were grown
      for 5-6 days (young) or 3 weeks (mature). Mature neurons acquired resistance to
      apoptosis caused by colchicine as well as NGF withdrawal. Neither cytochrome c
      release nor DNA fragmentation occurred. Both beading formation and subsequent
      fragmentation were delayed in mature neurons following NGF deprivation, treatment
      with colchicine, or in vitro Wallerian degeneration. Neuritic ATP levels of young
      ganglia decreased rapidly, while those of mature ganglia did so slowly during
      degeneration, although the basal levels of neuritic ATP of both ganglia were
      similar. Notably, mature neurites were resistant to fragmentation caused by NGF
      deprivation and capable of growing again after replenishment of NGF. This
      development of resistance to neurite degeneration in mature neurons may be
      thought as an important protective mechanism for the maintenance of the adult
      nervous system.

PMID- 18621036
TI  - GABAA receptors in deep cerebellar nuclei play important roles in mouse eyeblink
      conditioning.
AB  - The neural circuitry of eyeblink conditioning in rabbits has been studied in
      detail, however, the basic knowledge of eyeblink conditioning in mice remains
      limited. In the present study, we examined the role of the deep cerebellar nuclei
      (DCN) in mice in delay eyeblink conditioning and rotor rod test performance by
      using the gamma-aminobutyric acidA (GABA(A)) receptor agonist muscimol (MSC) and
      the GABA(A) receptor antagonist picrotoxin (PTX). Bilateral injections of MSC and
      PTX into the DCN significantly impaired motor coordination in the rotor rod test,
      however the performance recovered within 24 h after the injections. Bilateral
      injection of MSC and PTX significantly impaired learned eyeblink responses (LER)
      during the acquisition test. MSC-injected mice could not acquire LER, however,
      PTX-injected mice acquired LER latently, suggesting the distinctive effect of
      these drugs in DCN. Bilateral injection of MSC and PTX also impaired the
      retention of acquired LER during a 7-day performance test. Furthermore,
      ipsilateral injections of MSC and PTX impaired the acquired LER as much as
      bilateral injection of them. Contralateral MSC injections also impaired the
      expression of LER, but contralateral PTX injections only partially impaired
      eyeblink conditioning. These results suggest that GABA(A) receptors in bilateral
      DCN play important roles in both the acquisition and the expression of mouse
      eyeblink conditioning, and that GABA(A) receptors not only in ipsilateral but
      also in contralateral DCN are critical for the expression of LER.

PMID- 18621037
TI  - Isolating event-related potential components associated with voluntary control of
      visuo-spatial attention.
AB  - Attention-directing cues presented at fixation evoke several lateralized event
      related potential (ERP) components prior to the onset of visual targets. These
      components have been associated with the control of visuo-spatial attention, but
      the neuro-cognitive operations and neural generators of the components are still
      largely unknown. Here, we isolated cue-elicited ERP activity in different ways to
      home in on different neuro-cognitive operations and to gain a better
      understanding about the possible neuroanatomical sources of the cue-elicited ERP
      activities. To isolate lateralized cue-ERP activity, we compared shift-left and
      shift-right cue ERPs to shift-up cue ERPs. To measure all of the ERP activity
      related to attentional control, including spatially nonspecific activity that is
      removed in the process of isolating lateralized cue-ERP components, we compared
      shift-cue ERPs to neutral-cue (i.e., no-shift) ERPs. Isolated lateralized-ERP
      activity was seen in the contralateral-occipital lobe in the early phase of the
      cue-target interval and in the ipsilateral-occipital lobe in the late phase. The
      later, ipsilateral activity indicates that the late directing attention
      positivity (LDAP) reflected processing of the to-be-ignored location. The neutral
      cue isolation revealed a shift-related positivity over posterior scalp regions
      and a shift-related negativity over more anterior scalp regions. The spatio
      temporal sequence of shift-related activity observed on the scalp, together with
      estimates of distributed source activity underlying the shift-related ERP
      components, indicated that frontal and parietal regions of cortex participated in
      the control of attention and led to pre-target biasing in visual cortical areas.

PMID- 18621038
TI  - Early increases in serum S100B are associated with cerebral hemorrhage in a rat
      model of focal cerebral ischemia.
AB  - S100B is a 21-kD, Ca2+-binding protein that is mainly expressed in astroglial
      cells and Schwann cells in the nervous system. The S100B level in peripheral
      blood samples is reportedly elevated in patients with various central nervous
      system disorders including ischemic stroke. Since an elevated peripheral S100B
      level seems to be related closely to cerebral vascular damage involving a blood
      brain barrier (BBB) disruption, we hypothesized that the peripheral S100B levels
      may increase earlier and to a greater extent after stroke onset when the cerebral
      blood vessels are severely damaged and spontaneous cerebral hemorrhage exists. In
      the present study, the relationship between an increase in the serum S100B level
      and cerebral hemorrhage was investigated within 24 h of stroke onset. A rat model
      for focal cerebral ischemia using an intraluminal filament method was utilized
      because cerebral hemorrhage is sometimes observed as a result of vascular damage
      caused by the filament. Significant increases in the serum S100B levels of rats
      with cerebral hemorrhage were observed from 1 h after stroke onset, compared with
      the levels in rats without cerebral hemorrhage. The early increases in serum
      S100B were not correlated with the brain infarct volumes at 3 h after stroke.
      These findings suggest that the serum S100B level increases earlier, reflecting
      the existence of cerebral hemorrhage.

PMID- 18621039
TI  - Intra-periaqueductal gray matter injections of midazolam fail to alter anxiety in
      plus-maze experienced mice.
AB  - It is well known that prior experience to the elevated plus-maze increases the
      avoidance of rodents to the open arms and impairs the anxiolytic-like effect of
      benzodiazepines evaluated during a subsequent exposure to the maze, a phenomenon
      known as "one-trial tolerance". Centrally injected benzodiazepine drugs attenuate
      anxiety in some limbic structures, such as hypothalamus, amygdala and the
      midbrain periaqueductal gray (PAG). This study investigated the effects of intra
      PAG infusions of midazolam (MDZ) in maze-naive and maze-experienced mice. The
      antiaversive effects of MDZ (3.0 nmol and 30 nmol in 0.1 microl) were evaluated
      by prior injection of flumazenil (16 nmol/0.1 microl), a benzodiazepine receptor
      antagonist, into the same midbrain site. Test videotapes were scored for
      conventional measures of anxiety and locomotor activity, as well as a range of
      ethological measures related to risk assessment. In maze-naive mice, intra-PAG
      infusions of MDZ increased % open arm entries (3.0 nmol) and % open arm time (3.0
      and 30 nmol). These effects were observed in the absence of significant changes
      in locomotor activity, indicating a selective anxiolytic-like effect of MDZ. The
      antiaversive effects of MDZ were completely blocked by prior injection of
      flumazenil which in turn did not alter any other behavioral measure. In maze
      experienced mice, intra-PAG infusion of MDZ did not modify any behavioral
      measure. Taken together, present results corroborate previous studies
      demonstrating that GABA/benzodiazepine receptor complex located within the PAG
      plays a role on anxiety modulation in maze-naive mice as well as indicate its
      involvement in the OTT phenomenon.

PMID- 18621041
TI  - Establishing age/sex related serum creatinine reference intervals from hospital
      laboratory data based on different statistical methods.
AB  - BACKGROUND: This is a retrospective study on a large hospital database to
      establish age- and sex-related mean values and reference ranges for serum
      creatinine (Scr), obtained with an IDMS-traceable, enzymatic method, in a
      Caucasian population. METHODS: The database was filtered for unique entries to
      reduce the presence of correlated and pathological data. Three different
      statistical methods, a non-parametric method, the Bhattacharya procedure and a
      non-linear fit of the cumulative Gaussian distribution were used to estimate the
      serum creatinine-age dependency for men and women, from birth till 100 years of
      age. RESULTS: Scr increases with age, equal for boys and girls, up to 14 years
      and with a much steeper slope for boys than for girls between 14 and 20 years. We
      show that the Scr-age pattern is constant between 20 and 70 years with a mean of
      0.90 mg/dL [0.63-1.16 mg/dL] for men and 0.70 mg/dL [0.48-0.93 mg/dL] for women.
      Above 70, Scr starts to slowly increase again. CONCLUSIONS: Indirect methods
      confirm the available reference intervals from healthy-volunteer studies and add
      information on age-periods not covered by these studies. As such, indirect
      methods can be used complementary to healthy-volunteer studies.

PMID- 18621040
TI  - Effects of continuous hypoxia on energy metabolism in cultured cerebro-cortical
      neurons.
AB  - Mechanisms underlying hypoxia-induced neuronal adaptation have not been fully
      elucidated. In the present study we investigated glucose metabolism and the
      activities of glycolytic and TCA cycle enzymes in cerebro-cortical neurons
      exposed to hypoxia (3 days in 1% of O2) or normoxia (room air). Hypoxia led to
      increased activities of LDH (194%), PK (90%), and HK (24%) and decreased
      activities of CS (15%) and GDH (34%). Neurons were incubated with [1
      (13)C]glucose for 45 and 120 min under normoxic or hypoxic (120 min only)
      conditions and 13C enrichment determined in the medium and cell extract using 1H
      {13C}-NMR. In hypoxia-treated neurons [3-(13)C]lactate release into the medium
      was 428% greater than in normoxia-treated controls (45-min normoxic incubation)
      and total flux through lactate was increased by 425%. In contrast glucose
      oxidation was reduced significantly in hypoxia-treated neurons, even when
      expressed relative to total cellular protein, which correlated with the reduced
      activities of the measured mitochondrial enzymes. The results suggest that
      surviving neurons adapt to prolonged hypoxia by up-regulation of glycolysis and
      down-regulation of oxidative energy metabolism, similar to certain other cell
      types. The factors leading to adaptation and survival for some neurons but not
      others remain to be determined.

PMID- 18621042
TI  - Beneficial effects of vegetable oils (corn, olive and sunflower oils) and alpha
      tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin in
      rats.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin are widely
      used in the treatment of inflammation, fever and pain. However, NSAIDs cause
      gastric damage as a major adverse reaction. In this study, the effects of
      vegetable oils (corn, olive and sunflower oils) and alpha-tocopherol on anti
      inflammatory and gastrointestinal profiles of indomethacin were evaluated in
      rats. Results showed that indomethacin given with sunflower, corn and olive oils
      reduced paw edema induced by carrageenan by 79.5%, 74.0% and 60.5%, whereas
      individual indomethacin and diclofenac reduced paw edema by 56.2% and 50.7%,
      respectively. Furthermore, it has been found that the vegetable oils possess
      significant anti-inflammatory effect against paw edema when given alone. These
      results showed that the vegetable oils have beneficial effects on reduction paw
      edema induced by carrageenan. Besides, the administration of indomethacin
      together with the vegetable oils and alpha-tocopherol did not cause a
      statistically significant gastric damage in rats (P>0.05). However, indomethacin
      caused statistically significant gastric lesions as compared with untreated rats
      (P<0.05). Moreover, it was also found that the effects of the vegetable oils and
      alpha-tocopherol improved the levels of antioxidant defense systems in rat
      stomach tissues against oxidative damage. These results suggest that indomethacin
      as well as other NSAIDs do not have any adverse effect on the gastrointestinal
      tract when they are used together with vegetable oils and vitamin E or as the
      preparations of the oils.

PMID- 18621043
TI  - Rat urinary bladder-derived relaxant factor: studies on its nature and release by
      coaxial bioassay system.
AB  - The present study was designed to characterize the urinary bladder-derived
      relaxant factor that was demonstrated by acetylcholine-induced relaxation
      response in a coaxial bioassay system consisting of rat bladder as the donor
      organ and rat anococcygeus muscle as the assay tissue. The concentration
      dependent relaxation to acetylcholine (10 nM-1 mM) was inhibited by atropine but
      was not altered by the antagonists of calcitonin gene-related peptide (CGRP 8
      37), vasoactive intestinal peptide (VIP 6-28), tachykinin NK1 (L-732138),
      tachykinin NK2 (MEN-10376), tachykinin NK3 (SB-218795), purinergic P2 (PPADS) and
      adenosine (CGS 15943) receptors as well as alpha-chymotrypsin. Adenylate cyclase
      inhibitor SQ-22536 and protein kinase A inhibitor KT-5720 significantly inhibited
      the acetylcholine response while guanylate cyclase inhibitor ODQ, and protein
      kinase C inhibitor H-7 did not have any effect. The P2X agonist alpha,beta
      methylene ATP (10 nM-0.1 mM) also produced concentration-dependent relaxation
      response that was inhibited by PPADS, SQ-22536 and KT-5720 in the coaxial
      bioassay system. In bladder strips, acetylcholine and alpha,beta-methylene ATP
      elicited concentration-dependent contractions that were not altered in the
      presence of SQ-22536 and KT-5720. In conclusion, the urinary bladder-derived
      relaxant factor that was recognized by the coaxial bioassay system is neither a
      peptide of the bladder neurons nor a purinergic mediator but adenylate cyclase
      and protein kinase A are involved in its release and/or relaxant effect.
      Furthermore, activation of purinergic P2X receptors besides the muscarinic
      receptors leads to the release of this factor.

PMID- 18621044
TI  - Beneficial effects of treatment with cystamine on brain in NZB/W F1 mice.
AB  - The involvement of the central nervous system (CNS) or neuropsychosis has been
      reported in patients with systemic lupus erythematosus (SLE) and considered a
      major cause of long-standing functional impairment and mortality. However, little
      is known in the improvement of the brain abnormality in SLE. To investigate the
      effect and mechanism of cystamine on brain in SLE, NZB/W F1 mice were used as the
      animal model. Gel zymography, caspase-3 activity assay and Western blots were
      performed to elucidate the effect of cystamine. Significant reduction of matrix
      metalloproteinases (MMP)-9/MMP-2 ratio and urokinase-type plasminogen activator
      (uPA) expression was detected in brain of NZB/W F1 mice treated with cystamine as
      compared to control group. Significant increase of heat-shock protein (HSP)-70
      and HSP27 was detected in brain of NZB/W F1 mice treated with cystamine as
      compared to control group. Additionally, significant reduction of mitochondrial
      dependent apoptosis was observed in brain of NZB/W F1 mice treated with cystamine
      as compared to control group by increasing BCL-2 and reducing caspase-9, Bad, and
      Apaf-1 expression. Moreover, increased phosphorylated p65 (NF-kappaB) protein was
      observed in brain of NZB/W F1 mice treated with cystamine as compared to control
      group. These experimental results firstly demonstrated the beneficial effects of
      cystamine on brain in NZB/W F1 mice and suggested the therapeutic potential in
      patients with neuropsychiatric SLE (NP-SLE).

PMID- 18621045
TI  - Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin
      Na+, K+ ATPase complex.
AB  - Juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease) is the most common
      progressive neurodegenerative disorder of childhood. CLN3, the transmembrane
      protein underlying JNCL, is proposed to participate in multiple cellular events
      including membrane trafficking and cytoskeletal functions. We demonstrate here
      that CLN3 interacts with the plasma membrane-associated cytoskeletal and
      endocytic fodrin and the associated Na(+), K(+) ATPase. The ion pumping activity
      of Na(+), K(+) ATPase was unchanged in Cln3(-/-) mouse primary neurons. However,
      the immunostaining pattern of fodrin appeared abnormal in JNCL fibroblasts and
      Cln3(-/-) mouse brains suggesting disturbances in the fodrin cytoskeleton.
      Furthermore, the basal subcellular distribution as well as ouabain-induced
      endocytosis of neuron-specific Na(+), K(+) ATPase were remarkably affected in
      Cln3(-/-) mouse primary neurons. These data suggest that CLN3 is involved in the
      regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma
      membrane association of Na(+), K(+) ATPase. Most of the processes regulated by
      multifunctional fodrin and Na(+), K(+) ATPase are also affected in JNCL and Cln3
      deficiency implicating that dysregulation of fodrin cytoskeleton and non-pumping
      functions of Na(+), K(+) ATPase may play a role in the neuronal degeneration in
      JNCL.

PMID- 18621046
TI  - Cellular repressor of E1A-stimulated genes is a bona fide lysosomal protein which
      undergoes proteolytic maturation during its biosynthesis.
AB  - Cellular repressor of E1A-stimulated genes (CREG) has been reported to be a
      secretory glycoprotein implicated in cellular growth and differentiation. We now
      show that CREG is predominantly localized within intracellular compartments.
      Intracellular CREG was found to lack an N-terminal peptide present in the
      secreted form of the protein. In contrast to normal cells, CREG is largely
      secreted by fibroblasts missing both mannose 6-phosphate receptors. This is not
      observed in cells lacking only one of them. Mass spectrometric analysis of
      recombinant CREG revealed that the protein contains phosphorylated
      oligosaccharides at either of its two N-glycosylation sites. Cellular CREG was
      found to cosediment with lysosomal markers upon subcellular fractionation by
      density-gradient centrifugation. In fibroblasts expressing a CREG-GFP fusion
      construct, the heterologous protein was detected in compartments containing
      lysosomal proteins. Immunolocalization of endogenous CREG confirmed that
      intracellular CREG is localized in lysosomes. Proteolytic processing of
      intracellular CREG involves the action of lysosomal cysteine proteinases. These
      results establish that CREG is a lysosomal protein that undergoes proteolytic
      maturation in the course of its biosynthesis, carries the mannose 6-phosphate
      recognition marker and depends on the interaction with mannose 6-phosphate
      receptors for efficient delivery to lysosomes.

PMID- 18621047
TI  - TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in 124
      patients.
AB  - BACKGROUND & AIMS: Budd-Chiari syndrome (BCS) is a rare and life-threatening
      disorder secondary to hepatic venous outflow obstruction. Small series of BCS
      patients indicate that transjugular intrahepatic portosystemic shunt (TIPS) may
      be useful. However, the influence of TIPS on patient survival and factors that
      predict the outcome of TIPS in BCS patients remain unknown. METHODS: One hundred
      twenty-four consecutive BCS patients treated with TIPS in 6 European centers
      between July 1993 and March 2006 were followed until death, orthotopic liver
      transplantation (OLT), or last clinical evaluation. RESULTS: Prior to treatment
      with TIPS, BCS patients had a high Model of End Stage Liver Disease and high
      Rotterdam BCS prognostic index (98% of patients at intermediate or high risk)
      indicating severity of liver dysfunction. However, 1- and 5-year OLT-free
      survival were 88% and 78%, respectively. In the high-risk patients, 5-year OLT
      free survival was much better than that estimated by the Rotterdam BCS index (71%
      vs 42%, respectively). In the whole population, bilirubin, age, and international
      normalized ratio for prothrombin time independently predicted 1-year OLT-free
      survival. A prognostic score with a good discriminative capacity (area under the
      curve, 0.86) was developed from these variables. Seven out of 8 patients with a
      score >7 died or underwent transplantation vs 5 out of 114 patients with a score
      <7. CONCLUSIONS: Long-term outcome for patients with severe BCS treated with TIPS
      is excellent even in high-risk patients, suggesting that TIPS may improve
      survival. Furthermore, we identified a small subgroup of BCS patients with poor
      prognosis despite TIPS who might benefit from early OLT.

PMID- 18621048
TI  - The detection of flat and depressed colorectal lesions: which endoscopic imaging
      approach?

PMID- 18621049
TI  - B7-H1 on hepatocytes facilitates priming of specific CD8 T cells but limits the
      specific recall of primed responses.
AB  - BACKGROUND & AIMS: The requirement for costimulation of CD8 T-cell priming and
      restimulation by nonprofessional antigen-presenting cells is unresolved. Here, we
      investigated whether B7-H1 (CD274, PD-L1) on hepatocytes (HC) is involved in the
      specific activation of naive CD8 T cells or activated CD8 T blasts. METHODS:
      Naive or activated CD8 T cells from transgenic OT-I mice were primed/restimulated
      by peptide-pulsed HC, and their proliferation and effector response were
      determined. We used blocking monoclonal antibodies against B7-H1 and HC from B7
      H1-deficient mice to assign a costimulatory or coinhibitory role to B7-H1 for CD8
      T-cell priming/restimulation. RESULTS: Blockade of B7-H1 on HC down modulated
      interferon (IFN)-gamma production and proliferation of HC-primed CD8 T cells,
      indicating a costimulatory role for B7-H1 in priming CD8 T cells. In contrast,
      the PD-1/B7-H1 interaction inhibited proliferation and interferon-gamma release
      of effector/memory CD8 T blasts specifically restimulated by peptide-pulsed HC.
      CONCLUSIONS: B7-H1 differentially modulates the different stages of the specific
      CD8 T-cell response triggered by HC, and, whereas it costimulates priming and
      cytokine responses of naive CD8 T cells, it coinhibits their specific local
      recall of effector cytokine responses. The interaction of CD8 T cells with B7
      H1(+) HC can thus fine-tune proliferative and effector responses of specific CD8
      T cells reacting locally to nonprofessional antigen-presenting cells infected
      with hepatotropic agents.

PMID- 18621050
TI  - Intestinal deletion of Pofut1 in the mouse inactivates notch signaling and causes
      enterocolitis.
AB  - BACKGROUND & AIMS: Notch downstream targets are fundamental to intestinal cell
      lineage commitment and are suggested as therapeutic targets for colon cancer
      cells. However, the role of endogenous Notch signaling through receptor-ligand
      interaction, and effects of its longer term down-regulation on intestinal
      homeostasis, are unclear. METHODS: To address these issues, the gene encoding
      protein O-fucosyltransferase 1, an enzyme required for Notch ligand binding and
      thus activation of all Notch receptors, was deleted in the mouse intestinal and
      colonic epithelium, through Villin-Cre-mediated recombination. RESULTS: Pofut1
      deletion inactivated Notch signaling, giving rise to smaller but viable mice.
      These mice exhibited a large increase in all intestinal secretory cell lineages,
      which accumulated in the crypts, resulting in crypt hyperplasia. Although
      proliferating cells were largely reduced in the colon, the transit amplifying
      compartment was maintained in the upper crypts of the intestinal mucosa. By 9
      months, these perturbations in cell maturation altered mucus-associated gut
      microbiota and caused chronic intestinal inflammation, with evidence of bacterial
      translocation to the mesenteric lymph nodes, macrophage, and T-lymphocyte
      infiltration, and Th1/Th17 immune response. Dysplastic foci were also observed in
      Pofut1-deficient small intestine with occasional progression to tumor formation.
      CONCLUSIONS: Mucus hypersecretion upon Pofut1 inactivation is accompanied by
      alteration of the mucus-associated flora, which likely contributes to the
      development of enterocolitis. Therefore, these data identify important potential
      complications in strategies to target Notch signaling in therapeutic approaches
      to colon cancer.

PMID- 18621052
TI  - Comparative phylogeography reveals host generalists, specialists and cryptic
      diversity: Hexabothriid, microbothriid and monocotylid monogeneans from
      rhinobatid rays in southern Australia.
AB  - The phylogeography and host specificity of three monogenean species infecting
      different sites on the southern fiddler ray, Trygonorrhina fasciata
      (Rhinobatidae) in South Australia (SA) were studied: Branchotenthes octohamatus
      (Hexabothriidae: gills), Calicotyle australis (Monocotylidae: cloaca) and
      Pseudoleptobothrium aptychotremae (Microbothriidae: skin). Five rhinobatid
      species (Aptychotrema vincentiana, T. fasciata, Trygonorrhina sp. A, Aptychotrema
      rostrata and Rhinobatos typus) with distributions spanning west, south and east
      Australian coastal waters, were surveyed for monogeneans resembling the three
      species documented from T. fasciata in SA. The identities of hosts and parasites
      collected were investigated using the mitochondrial genes ND4 and Cytochrome b
      (cytb), respectively, in addition to the nuclear marker, Elongation factor 1
      alpha (EF1a) for Pseudoleptobothrium. Genetic analyses confirmed that B.
      octohamatus is geographically widespread and displays little genetic structure,
      suggesting high levels of gene flow. It was collected from four rhinobatid
      species throughout its distribution and is not, therefore, host specific. For C.
      australis, genetic analyses revealed two discrete populations with a genetic
      divergence of ~4%, one population occurring west of Bass Strait on two sympatric
      host species and the other population on the east coast, also occurring on
      sympatric host species. Similarly, for Pseudoleptobothrium, specimens collected
      west of Bass Strait were genetically distinct (~3.5%) from those collected to the
      east. However, on the east coast, a third Pseudoleptobothrium population was
      revealed, separated by a genetic distance of >11%, indicating a morphologically
      cryptic species. Host preferences were indicated for each Pseudoleptobothrium
      lineage. These genetic discoveries are discussed in relation to life history
      characteristics of each monogenean species, highlighting the value of
      phylogeographic analyses to understand the parasite-host relationship.

PMID- 18621051
TI  - Relationships between anaemia and parasitic infections in Kenyan schoolchildren:
      a Bayesian hierarchical modelling approach.
AB  - Anaemia is multi-factorial in origin and disentangling its aetiology remains
      problematic, with surprisingly few studies investigating the relative
      contribution of different parasitic infections to anaemia amongst schoolchildren.
      We report cross-sectional data on haemoglobin, malaria parasitaemia, helminth
      infection and undernutrition among 1523 schoolchildren enrolled in classes 5 and
      6 (aged 10-21 years) in 30 primary schools in western Kenya. Bayesian
      hierarchical modelling was used to investigate putative relationships. Children
      infected with Plasmodium falciparum or with a heavy Schistosoma mansoni
      infection, stunted children and girls were found to have lower haemoglobin
      concentrations. Children heavily infected with S. mansoni were also more likely
      to be anaemic compared with uninfected children. This study further highlights
      the importance of malaria and intestinal schistosomiasis as contributors to
      reduced haemoglobin levels among schoolchildren and helps guide the
      implementation of integrated school health programmes in areas of differing
      parasite transmission.

PMID- 18621053
TI  - Phylogenetic analysis of Spiroplasmas from three freshwater crustaceans
      (Eriocheir sinensis, Procambarus clarkia and Penaeus vannamei) in China.
AB  - Disease epizootics in freshwater culture crustaceans (crab, crayfish and shrimp)
      gained high attention recently in China, due to intensive developments of
      freshwater aquacultures. Spiroplasma was identified as a lethal pathogen of the
      above three freshwater crustaceans in previous studies. Further characterization
      of these freshwater crustacean Spiroplasma strains were analyzed in the current
      study. Phylogenetic position was investigated by analysis of partial nucleotide
      sequences of 16S ribosomal RNA (rRNA), gyrB and rpoB genes, together with
      complete sequencing of 23S rRNA gene and 16S-23S rRNA intergenetic spacer regions
      (ISRs). Phylogenetic analysis of these sequences showed that the above-mentioned
      three freshwater crustacean Spiroplasma strains were identical and had a close
      relationship with Spiroplasma mirum. Furthermore, the genomic size, serological
      studies and experimental infection characteristics confirmed that three
      freshwater crustacean Spiroplasma strains are a single species other than
      traditional S. mirum. Therefore, these data suggest that a single species of
      Spiroplasma infects all three investigated freshwater crustaceans in China, and
      is a potential candidate for a new species within the Spiroplasma genus. These
      results provide critical information for the further investigations in fresh
      aquaculture epizootics related to tremor diseases, caused by this infectious
      agent.

PMID- 18621054
TI  - Screening for antibacterial and antifungal activities in marine benthic
      invertebrates from northern Norway.
AB  - Benthic marine invertebrates collected from sub-Arctic regions of northern
      Norway, were found to be a promising source of novel bioactive compounds against
      human and fish pathogenic bacteria and fungi. Lyophilized material from seven
      species of ascidians, six sponges and one soft alcyonid coral were extracted with
      60% acidified acetonitrile (ACN). After separation into an ACN-rich phase (ACN
      extract) and an aqueous phase, and subsequent solid-phase extraction of the
      aqueous phase, fractions differing in polarity were obtained and screened for
      antibacterial and antifungal activities, along with the more lipophilic ACN
      extracts. Antimicrobial activity was determined against two gram-negative, two
      gram-positive bacteria, and two strains of fungi. Notably, all the invertebrate
      species in the study showed activity against all four strains of bacteria and the
      two strains of fungi. In general, the aqueous fractions displayed highest
      antimicrobial activity, and the most potent extracts were obtained from the
      colonial ascidian Synoicum pulmonaria which displayed activity against bacteria
      and fungi at a concentration of 0.02 mg/ml; the lowest concentration tested.

PMID- 18621055
TI  - Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by
      CNGA2 channels.
AB  - Epinephrine, through its action on beta-adrenoceptors, may induce endothelium
      dependent vascular dilation, and this action is partly mediated by a cytosolic
      Ca(2+) ([Ca(2+)](i)) change in endothelial cells. In the present study, we
      explored the molecular identity of the channels that mediate epinephrine-induced
      endothelial Ca(2+) influx and subsequent vascular relaxation. Patch clamp
      recorded an epinephrine- and cAMP-activated cation current in the primary
      cultured bovine aortic endothelial cells (BAECs) and H5V endothelial cells. L-cis
      diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated
      channels, diminished this cation current. Furthermore, this cation current was
      greatly reduced by a CNGA2-specific siRNA in H5V cells. With the use of
      fluorescent Ca(2+) dye, it was found that epinephrine and isoprenaline, a beta
      adrenoceptor agonist, induced endothelial Ca(2+) influx in the presence of
      bradykinin. This Ca(2+) influx was inhibited by L-cis-diltiazem and LY-83583, and
      by a beta(2)-adrenoceptor antagonist ICI-118551. CNGA2-specific siRNA also
      diminished this Ca(2+) influx in H5V cells. Furthermore, L-cis-diltiazem and LY
      83583 inhibited the endothelial Ca(2+) influx in isolated mouse aortic strips. L
      cis-diltiazem also markedly reduced the endothelium-dependent vascular dilation
      to isoprenaline in isolated mouse aortic segments. In summary, CNG channels,
      CNGA2 in particular, mediate beta-adrenoceptor agonist-induced endothelial Ca(2+)
      influx and subsequent vascular dilation.

PMID- 18621056
TI  - Changing the determinants of protein stability from covalent to non-covalent
      interactions by in vitro evolution: a structural and energetic analysis.
AB  - The three disulfide bonds of the gene-3-protein of the phage fd are essential for
      the conformational stability of this protein, and it unfolds when they are
      removed by reduction or mutation. Previously, we used an iterative in vitro
      selection strategy to generate a stable and functional form of the gene-3-protein
      without these disulfides. It yielded optimal replacements for the disulfide bonds
      as well as several stabilizing second-site mutations. The best selected variant
      showed a higher thermal stability compared with the disulfide-bonded wild-type
      protein. Here, we investigated the molecular basis of this strong stabilization
      by solving the crystal structure of this variant and by analyzing the
      contributions to the conformational stability of the selected mutations
      individually. They could mostly be explained by improved side-chain packing. The
      R29W substitution alone increased the midpoint of the thermal unfolding
      transition by 14 deg and the conformational stability by about 25 kJ mol(-1).
      This key mutation (i) removed a charged side chain that forms a buried salt
      bridge in the disulfide-containing wild-type protein, (ii) optimized the local
      packing with the residues that replace the C46-C53 disulfide and (iii) improved
      the domain interactions. Apparently, certain residues in proteins indeed play key
      roles for stability.

PMID- 18621057
TI  - A new model for growth factor activation: type II receptors compete with the
      prodomain for BMP-7.
AB  - Bone morphogenetic proteins (BMPs) are morphogens with long-range signaling
      activities. BMP-7 is secreted as a stable complex consisting of a growth factor
      noncovalently associated with two propeptides. In other transforming growth
      factor-beta-like growth factor complexes, the prodomain (pd) confers latency to
      the complex. However, we detected no difference in signaling capabilities between
      the growth factor and the BMP-7 complex in multiple in vitro bioactivity assays.
      Biochemical and biophysical methods elucidated the interaction between the BMP-7
      complex and the extracellular domains of its type I and type II receptors.
      Results showed that type II receptors, such as BMP receptor II, activin receptor
      IIA, and activin receptor IIB, competed with the pd for binding to the growth
      factor and displaced the pd from the complex. In contrast, type I receptors
      interacted with the complex without displacing the pd. These studies suggest a
      new model for growth factor activation in which proteases or other extracellular
      molecules are not required and provide a molecular mechanism consistent with a
      role for BMP receptors in the establishment of early morphogen gradients.

PMID- 18621058
TI  - Crystal structures of multiple GATA zinc fingers bound to DNA reveal new insights
      into DNA recognition and self-association by GATA.
AB  - The GATA family of transcription factors (GATA1-6) binds selected GATA sites in
      vertebrate genomes to regulate specific gene expression. Although vertebrate GATA
      factors have two highly conserved zinc finger motifs, how the two fingers act
      together to recognize functional DNA elements is not well understood. Here we
      determined the crystal structures of the C-terminal zinc finger of mouse GATA3
      bound to DNA containing two variously arranged GATA binding sites. Our structures
      and accompanying biochemical analyses reveal two distinct modes of DNA binding by
      GATA to closely arranged sites. One mode involves cooperative binding by two GATA
      factors that interact with each other through protein-protein interactions. The
      other involves simultaneous binding of the N-terminal zinc finger (N-finger) and
      the C-terminal zinc finger of the same GATA factor. Our studies represent the
      first crystallographic analysis of GATA zinc fingers bound to DNA and provide new
      insights into the DNA recognition mechanism by the GATA zinc finger. Our crystal
      structure also reveals a dimerization interface in GATA that has previously been
      shown to be important for GATA self-association. These findings significantly
      advance our understanding of the structure and function of GATA and provide an
      important framework for further investigating the in vivo mechanisms of GATA
      dependent gene regulation.

PMID- 18621059
TI  - Scrapie prion protein structural constraints obtained by limited proteolysis and
      mass spectrometry.
AB  - Elucidation of the structure of scrapie prion protein (PrP(Sc)), essential to
      understand the molecular mechanism of prion transmission, continues to be one of
      the major challenges in prion research and is hampered by the insolubility and
      polymeric character of PrP(Sc). Limited proteolysis is a useful tool to obtain
      insight on structural features of proteins: proteolytic enzymes cleave proteins
      more readily at exposed sites, preferentially within loops, and rarely in beta
      strands. We treated PrP(Sc) isolated from brains of hamsters infected with 263K
      and drowsy prions with varying concentrations of proteinase K (PK). After PK
      deactivation, PrP(Sc) was denatured, reduced, and cleaved at Cys179 with 2-nitro
      5-thiocyanatobenzoic acid. Fragments were analyzed by nano-HPLC/mass spectrometry
      and matrix-assisted laser desorption/ionization. Besides the known cleavages at
      positions 90, 86, and 92 for 263K prions and at positions 86, 90, 92, 98, and 101
      for drowsy prions, our data clearly demonstrate the existence of additional
      cleavage sites at more internal positions, including 117, 119, 135, 139, 142, and
      154 in both strains. PK concentration dependence analysis and limited proteolysis
      after partial unfolding of PrP(Sc) confirmed that only the mentioned cleavage
      sites at the N-terminal side of the PrP(Sc) are susceptible to PK. Our results
      indicate that besides the "classic" amino-terminal PK cleavage points, PrP(Sc)
      contains, in its middle core, regions that show some degree of susceptibility to
      proteases and must therefore correspond to subdomains with some degree of
      structural flexibility, interspersed with stretches of amino acids of high
      resistance to proteases. These results are compatible with a structure consisting
      of short beta-sheet stretches connected by loops and turns.

PMID- 18621060
TI  - A comparative computational analysis of protein sequences and literature mining
      classify 'orphan' neurotransmitter transporters.
AB  - Various sources of protein data, such as knowledgebases and scientific
      literature, are currently available, as are numerous tools for their analysis.
      The matter becomes one of choosing the tools that are most appropriate for the
      specific task and for the specific proteins. A combination of standard and
      alternative tools may lead to biologically significant results. Here, a
      computational classification of proteins is made using standard multiple sequence
      alignment in combination with an alternative method for analysis of hydropathy
      distribution in proteins. Both of these methods are applied to the Na+/Cl-
      dependent neurotransmitter symporters (NSSs), resulting in two alternative
      classifications. The classifications are validated and interpreted biologically
      by literature and knowledgebase annotation mining, producing a consensus
      classification. The classification leads to the identification and functional
      characterization of three families of largely structurally and functionally
      uncharacterized orphan NSSs. The literature and knowledgebase annotations are
      mined to functionally characterize the NSSs in these families. The presented work
      also demonstrates that, in specific cases, the analysis of the hydropathy
      distribution in proteins is capable of revealing functional properties of
      proteins.

PMID- 18621061
TI  - Genomic imprinting and kinship in the social Hymenoptera: what are the
      predictions?
AB  - The kinship theory of genomic imprinting predicts that conflicts of interest
      between parents can promote the evolution of opposed expression patterns of
      maternally and paternally derived alleles in the offspring. The social
      Hymenoptera (ants, some bees, and some wasps) are particularly suitable to test
      this theory, because a variety of social conflicts are predicted due to
      relatedness asymmetries between female and male nestmates that are a corollary of
      haplo-diploid sex determination. Here I argue that the kin-selection predictions
      for genomic imprinting in social Hymenoptera might in many cases be more complex
      than previously suggested, because the optimal strategy will have to take fitness
      effects in different castes and sexes into account.

PMID- 18621062
TI  - Quantifying the complexity of bat wing kinematics.
AB  - Body motions (kinematics) of animals can be dimensionally complex, especially
      when flexible parts of the body interact with a surrounding fluid. In these
      systems, tracking motion completely can be difficult, and result in a large
      number of correlated measurements, with unclear contributions of each parameter
      to performance. Workers typically get around this by deciding a priori which
      variables are important (wing camber, stroke amplitude, etc.), and focusing only
      on those variables, but this constrains the ability of a study to uncover
      variables of influence. Here, we describe an application of proper orthogonal
      decomposition (POD) for assigning importances to kinematic variables, using
      dimensional complexity as a metric. We apply this method to bat flight
      kinematics, addressing three questions: (1) Does dimensional complexity of motion
      change with speed? (2) What body markers are optimal for capturing dimensional
      complexity? (3) What variables should a simplified reconstruction of bat flight
      include in order to maximally reconstruct actual dimensional complexity? We
      measured the motions of 17 kinematic markers (20 joint angles) on a bat
      (Cynopterus brachyotis) flying in a wind tunnel at nine speeds. Dimensional
      complexity did not change with flight speed, despite changes in the kinematics
      themselves, suggesting that the relative efficacy of a given number of dimensions
      for reconstructing kinematics is conserved across speeds. By looking at subsets
      of the full 17-marker set, we found that using more markers improved resolution
      of kinematic dimensional complexity, but that the benefit of adding markers
      diminished as the total number of markers increased. Dimensional complexity was
      highest when the hindlimb and several points along digits III and IV were
      tracked. Also, we uncovered three groups of joints that move together during
      flight by using POD to quantify correlations of motion. These groups describe
      14/20 joint angles, and provide a framework for models of bat flight for
      experimental and modeling purposes.

PMID- 18621063
TI  - The interplay between predator's prey preference and environmental heterogeneity
      in food web long-term stability.
AB  - Prey preference of a predator is commonly used in models to analyze the timely
      issue of the relation among food web structure, diversity and stability. Given
      the variety of these terms in ecological literature, this work shows that domains
      of stability and species coexistence in food webs can be significantly altered by
      the chosen structure of predator's prey preference and environmental
      heterogeneity. Such results may bear upon issues in applied ecology, e.g.,
      species conservation, biological control. More generally, they may serve as a
      caution with respect to the robustness of some results of food web theory.

PMID- 18621064
TI  - A new SEIR epidemic model with applications to the theory of eradication and
      control of diseases, and to the calculation of R0.
AB  - We present a novel SEIR (susceptible-exposure-infective-recovered) model that is
      suitable for modeling the eradication of diseases by mass vaccination or control
      of diseases by case isolation combined with contact tracing, incorporating the
      vaccine efficacy or the control efficacy into the model. Moreover, relying on
      this novel SEIR model and some probabilistic arguments, we have found four
      formulas that are suitable for estimating the basic reproductive numbers R(0) in
      terms of the ratio of the mean infectious period to the mean latent period of a
      disease. The ranges of R(0) for most known diseases, that are calculated by our
      formulas, coincide very well with the values of R(0) estimated by the usual
      method of fitting the models to observed data.

PMID- 18621065
TI  - Modeling ventricular repolarization: effects of transmural and apex-to-base
      heterogeneities in action potential durations.
AB  - Heterogeneities in the densities of membrane ionic currents of myocytes cause
      regional variations in action potential duration (APD) at various intramural
      depths and along the apico-basal and circumferential directions in the left
      ventricle. This work extends our previous study of cartesian slabs to ventricular
      walls shaped as an ellipsoidal volume and including both transmural and apex-to
      base APD heterogeneities. Our 3D simulation study investigates the combined
      effect on repolarization sequences and APD distributions of: (a) the intrinsic
      APD heterogeneity across the wall and along the apex-to-base direction, and (b)
      the electrotonic currents that modulate the APDs when myocytes are embedded in a
      ventricular wall with fiber rotation and orthotropic anisotropy. Our findings
      show that: (i) the transmural and apex-to-base heterogeneities have only a weak
      influence on the repolarization patterns on myocardial layers parallel to the
      epicardium; (ii) the patterns of APD distribution on the epicardial surface are
      mostly affected by the apex-to-base heterogeneities and do not reveal the APD
      transmural heterogeneity; (iii) the transmural heterogeneity is clearly
      discernible in both repolarization and APD patterns only on transmural sections;
      (iv) the apex-to-base heterogeneity is clearly discernible only in APD patterns
      on layers parallel to the epicardium. Thus, in our orthotropic ellipsoidal wall,
      the complex 3D electrotonic modulation of APDs does not fully mix the effects of
      the transmural and apex-to-base heterogeneity. The intrinsic spatial
      heterogeneity of the APDs is unmasked in the modulated APD patterns only in the
      appropriate transmural or intramural sections. These findings are independent of
      the stimulus location (epicardial, endocardial) and of Purkinje involvement.

PMID- 18621066
TI  - Increased damage of exon 5 of p53 gene in workers from an arsenic plant.
AB  - Mutagenesis is a multistage process. Substitution mutations can be induced by
      base modified through alteration of pairing property. Mutations of exon 5 and 8
      of p53 gene have been found in most arsenicosis patients with precarcinomas and
      carcinomas, but never in arsenicosis individuals without precarcinomas and
      carcinomas. This study investigates whether base modification exists in exon 5
      and 8 of p53 gene, and explores the dose-effect relationship between damage of
      exon 5 of p53 gene and urinary arsenic. Concentrations of urinary 8
      hydroxydeoxyguanine (8-OHdG) are analyzed to identify the occurrence of DNA
      damage. The real-time PCR developed by Sikorsky et al. is applied to detect base
      modification in exon 5 and 8 of p53 gene for apparently healthy participants. Our
      results show that the mean total arsenic concentrations of two exposed groups
      from an arsenic plant are significantly elevated compared with the control group,
      and the damage level of exon 5 of the high-exposed group is significantly higher
      than that of the control group, but which does not happen in exon 8. The closely
      correlation between the damage index of exon 5 and urinary organic arsenic
      concentration are found. Concentration of 8-OHdG of the high-exposed group is
      significantly higher than that of the control group. These results imply that
      base modification in exon 5 of p53 gene can be induced by arsenic. In addition,
      our study suggests that the damage level of exon 5 is a useful biomarker to
      assess adverse health effect levels caused by chronic exposure to arsenic.

PMID- 18621067
TI  - Type-3 metabotropic glutamate receptors negatively modulate bone morphogenetic
      protein receptor signaling and support the tumourigenic potential of glioma
      initiating cells.
AB  - Targeted-therapies enhancing differentiation of glioma-initiating cells (GICs)
      are potential innovative approaches to the treatment of malignant gliomas. These
      cells support tumour growth and recurrence and are resistant to radiotherapy and
      chemotherapy. We have found that GICs express mGlu3 metabotropic glutamate
      receptors. Activation of these receptors sustained the undifferentiated state of
      GICs in culture by negatively modulating the action of bone morphogenetic
      proteins, which physiologically signal through the phosphorylation of the
      transcription factors, Smads. The cross-talk between mGlu3 receptors and BMP
      receptors was mediated by the activation of the mitogen-activated protein kinase
      pathway. Remarkably, pharmacological blockade of mGlu3 receptors stimulated the
      differentiation of cultured GICs into astrocytes, an effect that appeared to be
      long lasting, independent of the growth conditions, and irreversible. In in vivo
      experiments, a 3-month treatment with the brain-permeant mGlu receptor
      antagonist, LY341495 limited the growth of infiltrating brain tumours originating
      from GICs implanted into the brain parenchyma of nude mice. While clusters of
      tumour cells were consistently found in the brain of control mice, they were
      virtually absent in a large proportion of mice treated with LY341495. These
      findings pave the way to a new non-cytotoxic treatment of malignant gliomas based
      on the use of mGlu3 receptor antagonists.

PMID- 18621068
TI  - Assessing human 5-HT function in vivo with pharmacoMRI.
AB  - A number of novel ways of using magnetic resonance imaging (MRI) to visualise the
      action of drugs on animal and human brain (pharmacoMRI or phMRI) are becoming
      established tools in translational psychopharmacology. Using drugs with known
      pharmacology it is possible to investigate how neurotransmitter systems are
      involved in neural systems engaged by other processes, such as cognitive
      challenge (modulation phMRI) or to examine the acute effects of the drug itself
      in the brain (challenge phMRI). In this article we discuss the principles behind
      phMRI and review studies investigating the effect of serotonin (5-HT)
      manipulations. 5-HT modulation phMRI studies show the involvement of 5-HT in a
      broad range of neural processes ranging from motor function through 'cold'
      cognition, such as memory and response inhibition, to emotional processing. We
      highlight findings in brain areas that show some consistency or complementarity
      across studies, such as the ventrolateral orbitofrontal cortex where modulation
      by 5-HT is task-specific, and the amygdala in emotional processing where 5-HT is
      predominantly inhibitory. 5-HT challenge phMRI is promising but as yet few
      studies have been carried out. New ways of analysing phMRI data include
      connectivity analysis which holds the promise of going beyond identifying
      isolated areas of activation/modulation to understanding functional circuits and
      their neurochemistry. 5-HT phMRI now needs to be taken into patient populations
      and methods of investigating treatment effects need to be developed. If this is
      successful then phMRI will provide a genuinely exciting opportunity for the rapid
      development of better treatments for psychiatric conditions.

PMID- 18621069
TI  - Chemical synthesis and biochemical characterization of a biotinylated derivative
      of 17beta-estradiol with a long side chain covalently attached to its C-7alpha
      position.
AB  - High-affinity biotinylated derivatives of 17beta-estradiol (E2) are of value for
      isolation of various estrogen-binding proteins (including estrogen receptors) and
      also for studying protein-protein interactions involving these proteins. In this
      study, we developed a simplified route for the chemical synthesis of a
      biotinylated derivative of E2 (compound 7) with a side chain attached to its C
      7alpha position. Compound 7, i.e., 7alpha-{7-[8-(biotinamido)-octanamido]-heptyl}
      estradiol, could be readily synthesized from 6-keto-estradiol-3,17beta-di
      tetrahydropyranyl ether (compound 2, which can be prepared from E2), with a final
      yield of 36%. In vitro receptor-binding assay confirmed that the synthesized
      affinity ligand has a high binding affinity for both human estrogen receptor
      alpha and beta. When the affinity ligand (compound 7) was immobilized with avidin
      on an affinity column, it effectively bound human estrogen receptor alpha, and
      the receptor protein could be selectively eluted with a biotin-containing buffer.
      Using the same affinity ligand, prolyl 4-hydroxylase beta-subunit (also known as
      protein disulfide isomerase) was identified as one of the high-affinity E2
      binding proteins in the whole cytosolic protein mixture prepared from MCF-7 human
      breast cancer cells. Computational molecular modeling analysis showed that
      compound 7 can bind to human estrogen receptor alpha in a similar manner as ICI
      182,780 and raloxifene, and their binding energy values are also similar.

PMID- 18621070
TI  - Quantitative genetic models of sexual selection by male choice.
AB  - There are many examples of male mate choice for female traits that tend to be
      associated with high fertility. I develop quantitative genetic models of a female
      trait and a male preference to show when such a male preference can evolve. I
      find that a disagreement between the fertility maximum and the viability maximum
      of the female trait is necessary for directional male preference (preference for
      extreme female trait values) to evolve. Moreover, when there is a shortage of
      available male partners or variance in male nongenetic quality, strong male
      preference can evolve. Furthermore, I also show that males evolve to exhibit a
      stronger preference for females that are more feminine (less resemblance to
      males) than the average female when there is a sexual dimorphism caused by
      fertility selection which acts only on females.

PMID- 18621071
TI  - Characterization of antimicrobial peptides from the skin secretions of the
      Malaysian frogs, Odorrana hosii and Hylarana picturata (Anura:Ranidae).
AB  - Peptidomic analysis of norepinephrine-stimulated skin secretions from Hose's rock
      frog Odorrana hosii (Boulenger, 1891) led to the isolation of 8 peptides with
      differential antibacterial activities. Structural characterization demonstrated
      that the peptides belonged to the esculentin-1 (1 peptide), esculentin-2 (1
      peptide), brevinin-1 (2 peptides), brevinin-2 (2 peptides), and nigrocin-2 (2
      peptides) families of antimicrobial peptides. Similar analysis of skin secretions
      from the Malaysian fire frog Hylarana picturata (Boulenger, 1920) led to the
      isolation and characterization of peptides belonging to the brevinin-1 (2
      peptides), brevinin-2 (5 peptides), and temporin (1 peptide) families. The
      differences in antimicrobial activities of paralogous peptides provide insight
      into structure-activity relationships, emphasizing the importance of cationicity
      in determining potency. The substitution Lys11-->Gln in brevinin-1HSa
      (FLPAVLRVAAKIVPTVFCAISKKC) from O. hosii abolishes growth inhibitory activity
      against Escherichia coli but has no effect on the high potency (MIC = 8
      microg/ml) against Staphylococcus aureus. In contrast, the substitution (Gly4-
      >Asp) in brevinin-2PTb (GFKGAFKNVMFGIAKSAGKSALNALACKIDKSC) from H. picturata
      reduces activity against both E. coli and S. aureus. Cladistic analysis based
      upon the amino acid sequences of the brevinin-2 peptides from Asian frogs
      provides evidence for sister taxon relationships between O. hosii and O. livida
      and between H. picturata and H. guntheri.

PMID- 18621072
TI  - Immunization with cDNA of a novel P-III type metalloproteinase from the
      rattlesnake Crotalus durissus durissus elicits antibodies which neutralize 69% of
      the hemorrhage induced by the whole venom.
AB  - Zinc-dependent metalloproteinases play a key role in the hemorrhage induced by
      viperid bite envenoming. In this work we report the cloning and sequencing of the
      cDNA from a novel P-III type metalloproteinase from Crotalus durissus durissus
      venom glands. The recombinant plasmid was used for DNA immunization in mice using
      accelerate DNA-coated microparticles with the Gene Gun system. The results showed
      that there is no significant difference in the efficiency of the immunization in
      mice when gold or tungsten microparticles were used. A pool of the sera from mice
      immunized with the metalloproteinase encoding DNA neutralized the hemorrhagic
      activity of C. d. durissus venom. The co-immunization with DNA encoding the
      metalloproteinase and a plasmid encoding the murine IL-2 increased the number of
      mice which show a specific antibody response towards C. d. durissus venom
      antigens. The neutralizing ability of the produced antibodies demonstrates that
      DNA immunization with tungsten microparticles may be used in strategies for
      antivenom production.

PMID- 18621073
TI  - Development of process to produce polyvalent IgY antibodies anti-African snake
      venom.
AB  - Polyvalent anti-Bitis and anti-Naja antivenom IgY antibodies were prepared using
      B. arietans, B. nasicornis, B. rhinoceros, N. melanoleuca, and N. mossambica
      venoms to immunize chickens. Blood and eggs were collected before and during the
      10-month immunization period; the sera and yolk extracts were then prepared and
      assayed for the presence of antivenom antibodies by ELISA and Western blot
      methods. ELISA Antivenom antibody titers, referred to as U-ELISA/ml of serum or
      egg yolk extracts, absent in pre-immunization sera or yolk, increased sharply
      during the 4 weeks after immunization, reaching a plateau thereafter. Yolk
      extracts with high antivenom titers, as detected by ELISA were used to isolate
      and purify IgY. Purified IgY preparations recognized venom protein bands from 10
      to 20 kDa to 60 and 70 kDa, as shown by Western blot. Recovery of antivenom
      antibodies from the whole yolk was over 80%. Final preparations exhibited high
      antivenom activity (>100,000 U-ELISA/ml) as well as efficacy in neutralizing
      venom lethality (1,440 microg of IgY neutralize 62.2 LD(50) of venom), and were
      free of toxic products, pyrogen or bacterial and fungal contaminations.

PMID- 18621074
TI  - Retinotopic encoding of the direction aftereffect.
AB  - Kohn and Movshon [Kohn, A., & Movshon, J. (2003). Neuronal adaptation to visual
      motion in area MT of the macaque. Neuron, 39, 681-691; Kohn, A., & Movshon, J. A.
      (2004). Adaptation changes the direction tuning of macaque MT neurons. Nature
      Neuroscience, 7(7), 764-772] measured the contrast response functions of single
      neurons in MT (V5) before and after adaptation to high contrast gratings. They
      found that when gratings were smaller than the MT receptive field, so that
      adapting and test regions could be either co-localised or non-overlapping,
      adaptation was spatially specific. This led to the hypothesis that grating
      adaptation occurs in V1, where receptive fields are small and retinotopically
      organized, and that MT merely inherits this adaptation. We predicted that spatial
      specificity would be less for dot stimuli that probably adapt MT cells directly.
      Also, given recent contradictory claims that hMT primarily exhibits both
      spatiotopy [d'Avossa, G., Tosetti, M., Crespi, S., Biagi, L., Burr, D., &
      Morrone, M. (2006). Spatiotopic selectivity of BOLD responses to visual motion in
      human area MT. Nature Neuroscience, 10, 249-255] and retinotopy [Gardner, J. L.,
      Merriam, E. P., Movshon, J. A., & Heeger, D. J. (2008). Maps of visual space in
      human occipital cortex are retinotopic, not spatiotopic. The Journal of
      Neuroscience, 28, 3988-3999], we were interested in producing relevant
      psychophysical evidence using the direction aftereffect. In three experiments, we
      measured direction aftereffects (DAEs) induced and tested either with drifting
      gratings or drifting dots when stimulus location was changed both retinotopically
      and spatiotopically between adaptation and test; when retinotopic location only
      was changed; and when spatiotopic location only was changed. We predicted and
      found that spatial specificity was greater for gratings than for dots. We also
      found very small spatiotopic effects that call into question some recent claims
      that area MT exhibits a high degree of spatiotopicity.

PMID- 18621075
TI  - Characterization of SSR103800, a selective inhibitor of the glycine transporter-1
      in models predictive of therapeutic activity in schizophrenia.
AB  - On native human, rat and mouse glycine transporter-1(GlyT1), SSR130800 behaves as
      a selective inhibitor with IC50 values of 1.9, 5.3 and 6.8 nM, respectively. It
      reversibly blocked glycine uptake in mouse brain cortical homogenates, increased
      extracellular levels of glycine in the rat prefrontal cortex, and potentiated
      NMDA-mediated excitatory postsynaptic currents in rat hippocampal slices.
      SSR103800 (30 mg/kg, p.o.) decreased MK-801- and PCP-induced locomotor
      hyperactivity in rodents. SSR103800 (1 and 10 mg/kg, p.o.) attenuated social
      recognition deficit in adult rats induced by neonatal injections of PCP (10
      mg/kg, s.c., on post-natal day 7, 9 and 11). SSR103800 (3 mg/kg, p.o.)
      counteracted the deficit in short-term visual episodic-like memory induced by a
      low challenge dose of PCP (1 mg/kg, i.p.), in PCP-sensitized rats (10 mg/kg,
      i.p.). SSR103800 (30 mg/kg, i.p.) increased the prepulse inhibition of the
      startle reflex in DBA/1J mice. SSR103800 decreased defensive- and despair-related
      behaviors in the tonic immobility test in gerbils (10 and 30 mg/kg, p.o.) and in
      the forced-swimming procedure in rats (1 and 3 mg/kg, p.o.), respectively. These
      findings suggest that SSR103800 may have a therapeutic potential in the
      management of the core symptoms of schizophrenia and comorbid depression states.

PMID- 18621076
TI  - Toxic causes of mental illness are overlooked.
AB  - While proper brain function requires the complex interaction of chemicals
      perpetually occupied in purposeful biochemistry, it is well established that
      certain toxic substances have the potential to disrupt normal brain physiology
      and to impair neurological homeostasis. As well as headache, cognitive
      dysfunction, memory disturbance, and other neurological signs and symptoms,
      disruption of brain function may also manifest as subtle or overt alteration in
      thoughts, moods, or behaviors. Over the last four decades, there has been the
      unprecedented development and release of a swelling repertoire of potentially
      toxic chemicals which have the capability to inflict brain compromise. Although
      the ability of xenobiotics to induce clinical illness is well established, the
      expanding public health problem of widespread toxicant exposure in the general
      population is a relatively new phenomenon that has spawned escalating concern.
      The emerging area of clinical care involving the assessment and management of
      accrued toxic substances such as heavy metals, pesticides, plasticizers and other
      endocrine disrupting or neurotoxic compounds has not been fully appreciated by
      the medical community and has yet to be incorporated into the clinical practice
      of many consultants or primary care practitioners.

PMID- 18621077
TI  - Preclinical Torsades-de-Pointes screens: advantages and limitations of surrogate
      and direct approaches in evaluating proarrhythmic risk.
AB  - The successful development of novel drugs requires the ability to detect (and
      avoid) compounds that may provoke Torsades-de-Pointes (TdeP) arrhythmia while
      endorsing those compounds with minimal torsadogenic risk. As TdeP is a rare
      arrhythmia not readily observed during clinical or post-marketing studies,
      numerous preclinical models are employed to assess delayed or altered ventricular
      repolarization (surrogate markers linked to enhanced proarrhythmic risk). This
      review evaluates the advantages and limitations of selected preclinical models
      (ranging from the simplest cellular hERG current assay to the more complex in
      vitro perfused ventricular wedge and Langendorff heart preparations and in vivo
      chronic atrio-ventricular (AV)-node block model). Specific attention is paid to
      the utility of concentration-response relationships and "risk signatures" derived
      from these studies, with the intention of moving beyond predicting clinical QT
      prolongation and towards prediction of TdeP risk. While the more complex
      proarrhythmia models may be suited to addressing questionable or conflicting
      proarrhythmic signals obtained with simpler preclinical assays, further
      benchmarking of proarrhythmia models is required for their use in the robust
      evaluation of safety margins. In the future, these models may be able to reduce
      unwarranted attrition of evolving compounds while becoming pivotal in the
      balanced integrated risk assessment of advancing compounds.

PMID- 18621078
TI  - Functional brain abnormalities in psychiatric disorders: neural mechanisms to
      detect and resolve cognitive conflict and interference.
AB  - In the present article, we review functional neuroimaging studies on interference
      processing and performance monitoring in three groups of psychiatric disorders,
      (1) mood disorders, (2) schizophrenia, and (3) obsessive-compulsive disorder
      (OCD). Ad (1) Behavioral performance measures suggest an impaired interference
      resolution capability in symptomatic bipolar disorder patients. A series of
      neuroimaging analyses found alterations in the ACC-DLPFC system in mood disorder
      (unipolar depressed and bipolar) patients, putatively reflective of an abnormal
      interplay of monitoring and executive neurocognitive functions. Other studies of
      euthymic bipolar patients showed relatively decreased interference-related
      activation in rostroventral PFC which conceivably underlies defective inhibitory
      control. Ad (2) Behavioral Stroop studies revealed a specific performance pattern
      of schizophrenia patients (normal RT interference but increased error
      interference and RT facilitation) suggestive of a deficit in ignoring irrelevant
      (word) information. Moreover, reduced/absent behavioral post-error and post
      conflict adaptation effects suggest alterations in performance monitoring and/or
      adjustment capability in these patients. Neuroimaging findings converge to
      suggest a disorder-related abnormal neurophysiology in ACC which consistently
      showed conflict- and error-related hypoactivation that, however, appeared to be
      modulated by different factors. Moreover, studies suggest a specific deficit in
      context processing in schizophrenia, evidently related to activation reduction in
      DLPFC. Ad (3) Behavioral findings provide evidence for impaired interference
      resolution in OCD. Neuroimaging results consistently showed conflict- and error
      related ACC hyperactivation which--conforming OCD pathogenesis models--can be
      conclusively interpreted as reflecting overactive performance monitoring. Taken
      together, interference resolution and performance monitoring appeared to be
      fruitful concepts in the investigation of neurocognitive deficits in psychiatric
      disorders.

PMID- 18621079
TI  - Mouse model of focal cerebral ischemia using endothelin-1.
AB  - Intracerebral injection of the vasoconstrictor peptide, endothelin-1 (ET-1), has
      been used as a method to induce focal ischemia in rats. The relative technical
      simplicity of this model makes it attractive for use in mice. However, the effect
      of ET-1 on mouse brains has not been firmly established. In this study, we
      determined the ability of ET-1 to induce focal cerebral ischemia in four
      different mouse strains (CD1, C57/BL6, NOD/SCID, and FVB). In contrast to rats,
      intracerebral injection of ET-1 did not produce a lesion in any mouse strain
      tested. A combination of ET-1 injection with either CCA occlusion or N(G)-nitro-l
      arginine methyl ester (l-NAME) injection produced only a small infarct and its
      size was strain-dependent. A triple combination of CCA occlusion with co
      injection of ET-1 and l-NAME produced a lesion in all mouse strains tested, and
      this resulted in a significant motor deficit. However, lesion size was still
      relatively small and strain-dependent. This study shows that ET-1 has a much less
      potent effect for producing an infarct in mice than rats.

PMID- 18621080
TI  - Effects of estrous stage and time of day on prepulse inhibition in female rats.
AB  - Prepulse inhibition (PPI) of the acoustic startle response is a measure of
      sensory motor gating, and is affected in various neuropsychiatric disorders.
      Although PPI has been used extensively to study both the neural effects of such
      conditions, as well as in the search for animal models, a number of critical
      issues have been encountered. Published methods for testing PPI vary widely
      across many parameters, two of the most common being the phase of the light/dark
      cycle during which the subjects are tested and the inclusion or exclusion of
      females. While previous research has attempted to clarify the effect of these
      factors, results for both human and animal studies have often been contradictory.
      This study investigated the relevance of the estrous cycle and time of day as
      variables that may influence PPI in adult female Sprague-Dawley rats. Results
      indicate that PPI is not affected by estrous phase, but may be affected by the
      time of day of testing, particularly at higher prepulse levels. At the 86 dBs
      prepulse level, rats tested during the light phase of the light/dark cycle
      displayed significantly lowered PPI as compared to the animals tested during the
      dark phase. Additionally, other measures such as baseline startle, habituation
      and activity during testing did not vary across the estrous or light cycles.
      These findings indicate that while estrous phase does not have any effect on PPI
      in female Sprague-Dawley rats when tested under these parameters, the time of day
      during which testing occurs does have the potential to alter PPI.

PMID- 18621081
TI  - Recording of electrically evoked auditory brainstem responses (E-ABR) with an
      integrated stimulus generator in Matlab.
AB  - Electrical auditory brainstem responses (E-ABRs) of subjects with cochlear
      implants are used for monitoring the physiologic responses of early signal
      processing of the auditory system. Additionally, E-ABR measurements allow the
      diagnosis of retro-cochlear diseases. Therefore, E-ABR should be available in
      every cochlear implant center as a diagnostic tool. In this paper, we introduce a
      low-cost setup designed to perform an E-ABR as well as a conventional ABR for
      research purposes. The distributable form was developed with Matlab and the
      Matlab Compiler (The Mathworks Inc.). For the ABR, only a PC with a soundcard,
      conventional system headphones, and an EEG pre-amplifier are necessary; for E
      ABR, in addition, an interface to the cochlea implant is required. For our
      purposes, we implemented an interface for the Combi 40+/Pulsar implant (MED-EL,
      Innsbruck).

PMID- 18621082
TI  - Efficacy of orally administered Lobelia chinensis extracts on herpes simplex
      virus type 1 infection in BALB/c mice.
AB  - By a plaque reduction assay, methanolic extracts from Lobelia chinensis (LC)
      significantly blocked herpes simplex virus type 1 (HSV-1) replication in HeLa
      cells without apparent cytotoxicity. The 50% inhibitory concentration (IC(50)) of
      LC on HSV-1 replication is 139.2 microg/ml. To elucidate LC anti-HSV-1 activity
      in vivo, BALB/c mice were injected subcutaneously with HSV-1 (2.5 x 10(6)PFU/50
      microl), treated orally thrice a day with acyclovir (60 mg/kg/dose) or LC (20 and
      50 mg/kg/dose) for 7 days, and inspected daily for signs of disease. Data from
      the scoring system indicated that animals infected with HSV-1, developed
      progressive zoster lesions starting 2 days postinfection (p.i.) and appeared the
      most serious syndromes at 4-5 days p.i. In marked contrast to the results with
      control mice, treatment with acyclovir or 50 mg/kg/dose LC resulted in a
      sustained protective effect. The HSV-1 titers and DNA levels in ground skin
      samples were significantly reduced by LC. No toxic effect of LC on liver and
      kidney functions was apparent. These results indicated that LC was a potent
      inhibitor of the in vitro and in vivo replication of HSV-1.

PMID- 18621083
TI  - Heterologous array analysis in Heterobasidion: hybridisation of cDNA arrays with
      probe from mycelium of S, P or F-types.
AB  - Because of the close relatedness between three species of Heterobasidion annosum
      (P-type), Heterobasidion parviporum (S-type) and Heterobasidion abietinum (F
      type), we investigated the possible use of arrays from one species for studies of
      gene expression in the other. Clones containing partial cDNAs from 94
      identifiable genes expressed during spore germination and differentiation in H.
      parviporum were printed manually in six replications on nylon membranes. The
      membrane was hybridized with chemifluorescent labelled cDNA from actively growing
      mycelia of H. parviporum, H. annosum or H. abietinum, cultivated on a non
      selective substrate. Product-moment correlation coefficient varied between 0.81
      and 0.49. Due to the level of correlation, in the gene expression among the
      intersterility groups, we concluded that the cDNA array of one can be used to
      study gene expression in the others.

PMID- 18621085
TI  - A simple and effective method to overcome the inhibition of Fe to PCR.
AB  - Fe inhibition to PCR can be overcome by adding greatly excessive EDTA first, and
      then the same amount Mg(2+) as EDTA to PCR mix. By this method impure DNA was
      amplified successfully. DNA samples containing metals whose complexation constant
      with EDTA was much higher than Mg(2+) can also be amplified.

PMID- 18621084
TI  - An optimised PCR/T-RFLP fingerprinting approach for the investigation of
      protistan communities in groundwater environments.
AB  - Due to the scarcity or complete absence of higher organisms, protists may
      represent an important higher trophic level (above Prokaryotes) in the food webs
      of groundwater habitats. Nevertheless, the importance of aquifer protists,
      especially in contaminated groundwater environments, is poorly understood.
      Partly, this may be due to a lack of adequate PCR and fingerprinting approaches
      for protists in aquifers, which can be considered low in protistan or high in non
      target rRNA gene copy numbers. Therefore, we have validated the suitability of
      distinct eukaryote-targeted primer pairs and restriction endonucleases for T-RFLP
      fingerprinting of protistan communities. By in silico predictions, and by
      fingerprinting, cloning and sequencing of microeukaryote amplicons from
      hydrocarbon-contaminated aquifer sediment DNA, we show that the Euk20f/Euk516r
      primer set in combination with Bsh1236I digestion is best suited for the recovery
      of diverse protistan 18S rRNA lineages. In contrast to other tested primer sets,
      a preferred recovery of fungal and archaeal non-target amplicons was not
      observed. In summary, we present an optimised microeukaryote-targeted PCR/T-RFLP
      fingerprinting approach which may be of value for the characterisation of
      protistan communities in groundwater and other habitats.

PMID- 18621086
TI  - Cardiovascular costs of emotion suppression cross ethnic lines.
AB  - Previous research has shown that inhibiting emotion-expressive behavior (emotion
      suppression) leads to increased sympathetic activation of the cardiovascular
      system [Gross, J.J. and Levenson, R.W. (1993). Emotional suppression: physiology,
      self-report, and expressive behavior. J. Pers. Soc. Psychol. 64(6), 970-986].
      Ethnic differences have been reported in how frequently suppression is used as an
      emotion regulation strategy [Gross, J.J. and John, O. (2003). Individual
      differences in two emotion regulation processes: implications for affect,
      relationships, and well-being. J. Pers. Soc. Psychol. 85(2), 348-362]; however,
      it remains unknown whether there are ethnic differences in the physiological
      consequences of suppression. To test this, 168 participants from four ethnic
      groups (African American, Chinese American, European American, Mexican American)
      watched a disgust-eliciting film clip; half were instructed to suppress their
      emotions and half simply watched the film. Consistent with previous research,
      suppression was associated with decreased facial behavior, increased
      cardiovascular activation, and no impact on subjective emotional experience.
      Ethnicity failed to moderate these effects, indicating the generality of the
      cardiovascular consequences of emotion suppression across ethnic background.

PMID- 18621087
TI  - Evidence for interferon production and its correlation with YF 17DD vaccine virus
      yields in primary chick embryo cells.
AB  - Early experiments have resulted in the establishment of an efficient methodology
      for the production of a yellow fever vaccine in chicken embryo fibroblasts (CEF)
      using the 17DD virus strain [Freire, M.S., Mann, G.F., Marchevsky, R.S.,
      Yamamura, A.M., Almeida, L.F., Jabor, A.V., Malachias, J.M., Coutinho, E.S.,
      Galler, R., 2005. Production of yellow fever 17DD vaccine virus in primary
      culture of chicken embryo fibroblasts: yields, thermo and genetic stability,
      attenuation and immunogenicity. Vaccine 23, 2501-2512]. To investigate the role
      of the interferon system in vaccine virus yields, CEF cultures seeded at high and
      low cell densities and infected with the yellow fever 17DD virus were used. The
      supernatants of these cultures were tested for the presence of interferon by an
      assay based on the reduction of cytopathic effect of a challenge virus (Sindbis),
      for the enzymatic activity of the interferon-induced 2',5'-oligoadenylate
      synthetase and for the expression of 2',5'-oligoadenylate synthetase mRNA. The
      presence of interferon and its influence in the replication of yellow fever 17DD
      virus in CEF cultures was clearly demonstrated.

PMID- 18621089
TI  - Functional analysis of structural motifs in dicistroviruses.
AB  - The family Dicistroviridae is composed of positive-stranded RNA viruses which
      have monopartite genomes. These viruses carry genome-linked virus proteins (VPg)
      and poly (A) tails. The 5' untranslated region (UTR) is approximately 500
      nucleotides and contains an internal ribosome entry site (IRES). These features
      resemble those of vertebrate picornaviruses, but dicistroviruses have other
      distinct characteristics. Picornaviruses have a single large open reading frame
      (ORF) encoding the capsid proteins at the 5'-end and the replicases at the 3'
      end. In contrast, dicistroviruses have two nonoverlapping ORFs. The 5'-proximal
      ORF encodes the replicases and the 3'-proximal ORF encodes the capsid proteins.
      Usually, positive-stranded viruses which have capsid protein genes in the 3' part
      of the genome produce subgenomic RNA for synthesis of the capsid proteins,
      because abundant quantities of the capsid proteins are required for the viral
      replication cycle. In dicistroviruses, translation of the capsid proteins is
      controlled by an additional IRES. This IRES is located in the intergenic region
      (IGR) between the replicase and capsid coding regions, and mediates the
      initiation of translation for the capsid proteins. The IGR-IRES has a multiple
      stem-loop structure containing three pseudoknots. We describe the characteristics
      of dicistroviruses, including the RNA elements and viral proteins.

PMID- 18621090
TI  - Use of the BioDis to generate a physiologically relevant IVIVC.
AB  - In the last decades there has been continual interest in site-specific delivery
      to the colon. Recently, new types of site-specific delivery formulations have
      been developed for the treatment of ulcerative colitis and other colon related
      diseases. The aim of the present study was to establish a physiologically
      relevant IVIVC for two prototypes using a prospective in vitro study. Caffeine, a
      drug being absorbed along the entire gastrointestinal tract, was selected as a
      model drug. USP apparatus 3, the BioDis, was used for all experiments and the
      passage through the gastrointestinal tract was simulated with a physiologically
      based pH-gradient. Subsequently, the fraction of drug released in vitro was
      compared with the fraction of drug released in vivo, which was determined in
      humans in a separate study. Results indicated that the BioDis method is very
      useful in terms of predicting the site/timing and extent of drug release from the
      prototypes, since an a priori IVIVC could be established. Moreover, from the
      results generated in the present study, it is obvious that novel pH- and time
      based multi-unit formulations would improve selectivity of drug delivery to the
      distal ileum and the colon and therefore might be very helpful in the treatment
      of colonic diseases.

PMID- 18621088
TI  - Frameshifting RNA pseudoknots: structure and mechanism.
AB  - Programmed ribosomal frameshifting (PRF) is one of the multiple translational
      recoding processes that fundamentally alters triplet decoding of the messenger
      RNA by the elongating ribosome. The ability of the ribosome to change
      translational reading frames in the -1 direction (-1 PRF) is employed by many
      positive strand RNA viruses, including economically important plant viruses and
      many human pathogens, such as retroviruses, e.g., HIV-1, and coronaviruses, e.g.,
      the causative agent of severe acute respiratory syndrome (SARS), in order to
      properly express their genomes. -1 PRF is programmed by a bipartite signal
      embedded in the mRNA and includes a heptanucleotide "slip site" over which the
      paused ribosome "backs up" by one nucleotide, and a downstream stimulatory
      element, either an RNA pseudoknot or a very stable RNA stem-loop. These two
      elements are separated by six to eight nucleotides, a distance that places the 5'
      edge of the downstream stimulatory element in direct contact with the mRNA entry
      channel of the 30S ribosomal subunit. The precise mechanism by which the
      downstream RNA stimulates -1 PRF by the translocating ribosome remains unclear.
      This review summarizes the recent structural and biophysical studies of RNA
      pseudoknots and places this work in the context of our evolving mechanistic
      understanding of translation elongation. Support for the hypothesis that the
      downstream stimulatory element provides a kinetic barrier to the ribosome
      mediated unfolding is discussed.

PMID- 18621091
TI  - Effect of BDNF val66met polymorphism on age-related amygdala volume changes in
      healthy subjects.
AB  - Brain-derived neurotrophic factor (BDNF) has been implicated in the mechanism of
      age-related regional brain volumetric changes. Healthy volunteers with the valine
      to methionine polymorphism at codon 66 of the BDNF gene (val66met) exhibit
      decreased volume of a number of brain structures, including hippocampus, temporal
      and occipital lobar gray matter volumes, and a negative correlation between age
      and the volume of bilateral dorsolateral prefrontal cortices. We sought to
      characterize the relationship between age, BDNF and amygdala volumes among
      healthy volunteers. We measured amygdala volumes in 55 healthy, right-handed
      volunteers who underwent structural magnetic resonance imaging (MRI) and were
      also characterized demographically and genotyped with respect to BDNF. Using an
      ANCOVA model, we found that amygdala volumes were inversely correlated with age
      in BDNF val66met carriers but not in non-carriers. This is the first report of
      age-related BDNF val66met polymorphism effects on amygdala volume.

PMID- 18621093
TI  - The importance of RNA binding proteins in preproinsulin mRNA stability.
AB  - A dynamic production of insulin is necessary for proper glucose homeostasis. In
      order to generate enough insulin available for exocytosis in response to the
      demands of the organism, the level of preproinsulin mRNA in the pancreatic beta
      cell needs to fluctuate. In animal models for type 2 diabetes the contents of
      preproinsulin mRNA are lowered, which might suggest that an impaired metabolism
      of preproinsulin mRNA contributes to the development of glucose intolerance and
      diabetes. Thus, it is of importance to understand the mechanisms by which
      preproinsulin mRNA levels are regulated. Although extensively studied, there are
      aspects of the regulation of insulin gene expression that still remain enigmatic.
      Our understanding of insulin gene transcription has improved considerably the
      last 20 years, but less effort has been invested into the control of
      preproinsulin mRNA stability. The preproinsulin mRNA has a long half-life and
      changes in preproinsulin mRNA stability, induced by glucose, are likely to be
      regulated through specific mechanisms. Recent findings indicate that the
      polypyrimidine tract-binding protein (PTB), also named hnRNP I, by binding to the
      3'-UTR (untranslated region) of the preproinsulin mRNA molecule, stabilizes the
      messenger, thereby participating in the glucose-induced increase in preproinsulin
      mRNA. This review will focus both on recent findings pertinent to PTB function in
      general, and on the specific role of PTB on the production of insulin in beta
      cells. We will also discuss the putative co-operativity between PTB and other
      proteins in the control of preproinsulin mRNA stability, and review beta-cell
      signaling events that may control the mRNA stabilizing effect of PTB.

PMID- 18621092
TI  - Role of biotransformation in 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione-induced
      hepatotoxicity in Fischer 344 rats.
AB  - Cytochrome P450 (CYP)-mediated metabolism in the thiazolidinedione (TZD) ring may
      contribute to the hepatotoxicity of the insulin-sensitizing agents such as
      troglitazone. We were interested in determining if biotransformation could also
      be a factor in the liver damage associated with another TZD ring containing
      compound, 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT). Therefore,
      hepatotoxic doses of DCPT (0.6 or 1.0 mmol/kg, i.p.) were administered to male
      Fischer 344 rats after pretreatment with vehicle, 1-aminobenzotriazole (ABT, non
      selective CYP inhibitor) and troleandomycin (TAO, CYP3A inhibitor).
      Alternatively, rats were pretreated with vehicle or the CYP3A inducer
      dexamethasone (DEX) prior to a non-toxic DCPT dose (0.2 mmol/kg, i.p.). Vehicle-,
      ABT-, TAO- and DEX-only control groups were also run. Toxicity was assessed 24 h
      after DCPT administration. Both hepatotoxic doses of DCPT induced elevations in
      serum alanine aminotransferase (ALT) levels that were attenuated by ABT or TAO
      pretreatment. Liver sections from rats that received vehicle+DCPT revealed areas
      of gross necrosis and neutrophil invasion, whereas sections from ABT+DCPT and
      TAO+DCPT rats showed minor changes compared to controls. DEX pretreatment
      potentiated ALT levels associated with the non-toxic DCPT dose. Furthermore,
      DEX+DCPT rat liver sections exhibited hepatic injury when compared against rats
      that received vehicle+DCPT. Blood urea nitrogen levels, urinalysis and kidney
      morphology were not markedly altered by any combination of pretreatments or
      treatments. Enzyme activity and Western blotting experiments with rat liver
      microsomes confirmed the effects of the various pretreatments. Our results
      suggest that hepatic CYP3A isozymes may be involved in DCPT-induced liver damage
      in male rats. We believe this is the first report demonstrating that modulation
      of the biotransformation of a TZD ring-containing compound can alter
      hepatotoxicity in a common animal model.

PMID- 18621094
TI  - Impact of metabolic abnormalities for beta cell function: clinical significance
      and underlying mechanisms.
AB  - It is firmly established that poor metabolic control in diabetes inhibits beta
      cell function. Chronic hyperglycaemia is probably the most important factor,
      exerting both primary negative effects (by glucose per se and/or metabolites) and
      secondary ones (by beta cell exhaustion). Dyslipidemia in diabetes aggravates the
      glucose effects both by inducing insulin resistance and by direct effects on beta
      cells. Much experimental and some clinical evidence indicates that therapies that
      promote "beta cell rest" such as early and intensive insulin treatment and K-ATP
      channel blockers can be beneficial.

PMID- 18621095
TI  - Attenuation of naloxone-induced Vc pERK hyper-expression following capsaicin
      stimulation of the face in aged rat.
AB  - In order to clarify the effect of age-related change in trigeminal nociception,
      phosphorylation of extracellular signal-regulated kinase (pERK) in trigeminal
      spinal subnucleus caudalis (Vc) and upper cervical spinal cord neurons were
      studied in the aged rats following subcutaneous capsaicin injection into the
      whisker pad. A large number of pERK-LI cells was expressed in the superficial
      laminae of Vc and upper cervical spinal cord in adult and aged rats following
      subcutaneous capsaicin injection into the whisker pad region. The number of pERK
      LI cells was largest at about 2.0mm caudal from the obex and gradually decreased
      in their numbers in more rostral and caudal sections. The rostro-caudal
      distribution profile of pERK-LI cells expressed after subcutaneous capsaicin
      injection into whisker pad was similar in adult and aged rats. The number of pERK
      LI cells was slightly, but not significantly larger in aged rats compared with
      that of adults. Pretreatment with naloxone significantly increased the number of
      capsaicin-induced pERK-LI cells in adult rats but not in aged rats. The present
      findings suggest that the descending modulation system impaired with advancing
      age, resulting in the abnormal pain sensation in aged rats.

PMID- 18621096
TI  - Unexpected finding of a marked non-neuronal cholinergic system in human knee
      joint synovial tissue.
AB  - The cholinergic anti-inflammatory pathway is a newly discovered pathway. Another
      recent concept is the existence of a non-neuronal cholinergic system that has, so
      far, been defined for human tendons, intestine, airways and urinary bladder. The
      existence of such a system in joint synovial tissue is yet to be described. We
      therefore aimed to investigate the expression of choline acetyltransferase (ChAT)
      at both the protein and mRNA level using immunohistochemistry and in situ
      hybridisation, in human knee synovial tissue from rheumatoid arthritis (RA) and
      osteoarthritis (OA) patients. The biopsy samples were collected from patients
      undergoing knee prosthetic surgery. Our results show that both ChAT protein and
      mRNA is expressed in fibroblast-like and mononuclear-like cells, and to some
      extent in blood vessel walls in the synovial tissue. The mononuclear-like cells
      showing ChAT expression were scattered throughout the synovial tissue or located
      in association with lymphoid aggregates. Thus, we present the first evidence of
      the existence of a marked non-neuronal cholinergic system in human synovial
      tissue. The existence of this system could lead to the development of alternative
      medications to those currently in use. The system might function as a cholinergic
      anti-inflammatory pathway in synovial tissue. Our observations show that synovial
      tissue of patients with marked RA or OA, a tissue in which cholinergic
      innervation is not proven to exist, is supplied with acetylcholine via production
      in non-neuronal cells within the tissue.

PMID- 18621097
TI  - Activation of metabotropic glutamate 5 (mGlu5) receptors induces spontaneous
      excitatory synaptic currents in layer V pyramidal cells of the rat prefrontal
      cortex.
AB  - Serotonin and norepinephrine, in addition to direct postsynaptic excitatory
      effects, also enhances glutamate release onto layer V pyramidal cells of the
      prefrontal cortex/neocortex via G(q/11)-coupled 5-hydroxytryptamine(2A) (5
      HT(2A)) and alpha(1)-adrenergic receptors, respectively. Therefore, the present
      study was designed to test whether a metabotropic glutamate (mGlu) receptor
      subtype also coupled to G(q/11)-proteins, the mGlu5 receptor, also induces EPSCs
      when recording from layer V cortical pyramidal cells of the rat medial prefrontal
      cortex (mPFC). The mGlu1/5 receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG)
      induces EPSCs at a similar frequency as a near-maximally effective 5-HT
      concentration. The mGlu5 receptor negative allosteric modulator 2-methyl-6
      (phenylethynyl)pyridine (MPEP, 300 nM) potently blocked DHPG-induced EPSCs.
      Previous work has suggested that activation of 5-HT(2A) and OX2 receptors induces
      glutamate release, while mGlu2, mGlu4, and mGlu8 receptor activation suppress
      transmitter release from thalamocortical terminals. Taken together with past
      results, these findings suggest that mGlu2, mGlu4, mGlu5 and mGlu8 may all act to
      modulate glutamate release from afferents impinging on layer V pyramidal cells of
      the mPFC. These findings further suggest that monoamines, neuropeptides and
      glutamate itself all enhance the excitability of prefrontal cortical output cells
      indirectly via modulation of glutamate release.

PMID- 18621098
TI  - Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex.
AB  - Stress-mediated loss of synaptogenesis in the hippocampus appears to play a role
      in depressive and mood disorders. However, little is known about the effect of
      stress/depression on the plasticity and survival of cortical neurons. In this
      report, we have examined whether chronic stress increases the vulnerability of
      neurons in the rat cortex. We have used a chronic unpredictable mild stress (CMS)
      as a rat model of depression. CMS (5 weeks treatment) produced anedonia and
      increased corticosterone levels. These effects were accompanied by a detectable
      increase in caspase-3 positive neurons in the cerebral cortex, suggesting
      apoptosis. Desipramine (DMI), a well known antidepressant, reversed the pro
      apoptotic effect of CMS. These results suggest that antidepressants may reduce
      the pathological changes seen in stress-induced depressive disorders.

PMID- 18621099
TI  - Glutaredoxin systems.
AB  - Glutaredoxins utilize the reducing power of glutathione to maintain and regulate
      the cellular redox state and redox-dependent signaling pathways, for instance, by
      catalyzing reversible protein S-glutathionylation. Due to the general importance
      of these processes, glutaredoxins have been implied in various physiological and
      disease-related conditions, such as immune defense, cardiac hypertrophy, hypoxia
      reoxygenation insult, neurodegeneration and cancer development, progression as
      well as treatment. The past years have seen an impressive gain of knowledge
      regarding new glutaredoxin systems and functions. This is true both with respect
      to new functions in redox regulation and also with respect to unexpected new ties
      to iron metabolism and iron-sulfur cluster biosynthesis. The aim of this review
      is to provide a state-of-the-art overview over these recent discoveries with a
      focus on aspects related to human health.

PMID- 18621100
TI  - Import of hybrid forms of CYP11A1 into yeast mitochondria.
AB  - Heterologous expression in yeast of mCYP11A1 fusions with different topogenic
      signals of yeast mitochondrial proteins for artificial channeling to different
      translocases of the inner membrane was used to gain insight in the mechanism of
      its topogenesis in mitochondria. To ensure insertion of the CYP11A1 domain into
      the inner mitochondrial membrane during the process of translocation, topogenic
      sequences containing transmembrane segments of Bcs1p(1-83), DLD(1-72), and full
      sized AAC protein were used when constructing modified forms of CYP11A1, and the
      Su9(1-112) addressing signal was included to stimulate membrane insertion of
      CYP11A1 after its translocation to the matrix. Alternatively, to promote slippage
      of the hybrid molecules into the matrix, the hybrid of mCYP11A1 with the
      precursor of steroidogenic mitochondria matrix protein adrenodoxin (preAd) was
      designed. The extra sequences used for intramitochondrial sorting of CYP11A1
      apparently ensured predicted topology of hybrid molecules in yeast mitochondria.
      All of the addressing sequences, containing transmembrane domains, provided
      effective insertion of the hybrid proteins AAC-mCYP11A1, Bcs1p(1-83)-mCYP11A1,
      DLD(1-72)-mCYP11A1 and Su9(1-116)-mCYP11A1 into the inner membrane. preAd
      mCYP11A1 hybrid molecules were shown to be translocated across the inner membrane
      and tightly associated with the membrane on its matrix side but not membrane
      inserted. Measuring specific activities of hybrid proteins in the mitochondrial
      fractions upon addition of Ad and AdR showed that the hybrids predetermined for
      cotranslocational insertion of CYP11A1 into the inner membrane were more active
      in the reaction of cholesterol side-chain cleavage than those destined for
      insertion on the matrix side of the IM, the Ad-mCYP11A1 hybrid demonstrating only
      residual enzyme activity. The data obtained reinforce the proposal that complete
      transfer of the polypeptide chain into the matrix is not a necessary stage in its
      topogenesis, but rather persistent interaction of the polypeptide chain with the
      membrane during the process of translocation is of importance for heme binding,
      folding and membrane insertion.

PMID- 18621101
TI  - Enhancement of anxiety, facilitation of avoidance behavior, and occurrence of
      adult-onset obesity in mice lacking mitochondrial cyclophilin D.
AB  - In this report, we have assessed the behavioral responses of mice missing the
      Ppif gene (CyPD-KO), encoding mitochondrial cyclophilin D (CyPD). Mitochondrial
      CyPD is a key modulator of the mitochondrial permeability transition which is
      involved in the regulation of calcium- and oxidative damage-induced cell death.
      Behavioral screening of CyPD-KO mice (ranging between 4 and 15 months of age) was
      accomplished using a battery of behavioral paradigms which included testing of
      motor functions, exploratory activity, and anxiety/emotionality, as well as
      learning and memory skills. We found that, compared with wild-type mice, CyPD-KO
      mice were (i) more anxious and less explorative in open field and elevated plus
      maze and (ii) performed better in learning and memory of avoidance tasks, such as
      active and passive avoidance. However, the absence of CyPD did not alter the
      nociceptive threshold for thermal stimuli. Finally, deletion of CyPD caused also
      an abnormal accumulation of white adipose tissue resulting in adult-onset
      obesity, which was not dependent on increased food and/or water intake. Taken
      together, our results suggest a new fundamental role of mitochondrial CyPD in
      basal brain functions and body weight homeostasis.

PMID- 18621102
TI  - Timing of sound-evoked potentials and spike responses in the inferior colliculus
      of awake bats.
AB  - Neurons in the inferior colliculus (IC), one of the major integrative centers of
      the auditory system, process acoustic information converging from almost all
      nuclei of the auditory brain stem. During this integration, excitatory and
      inhibitory inputs arrive to auditory neurons at different time delays. Result of
      this integration determines timing of IC neuron firing. In the mammalian IC, the
      range of the first spike latencies is very large (5-50 ms). At present, a
      contribution of excitatory and inhibitory inputs in controlling neurons' firing
      in the IC is still under debate. In the present study we assess the role of
      excitation and inhibition in determining first spike response latency in the IC.
      Postsynaptic responses were recorded to pure tones presented at neuron's
      characteristic frequency or to downward frequency modulated sweeps in awake bats.
      There are three main results emerging from the present study: (1) the most common
      response pattern in the IC is hyperpolarization followed by depolarization
      followed by hyperpolarization, (2) latencies of depolarizing or hyperpolarizing
      responses to tonal stimuli are short (3-7 ms) whereas the first spike latencies
      may vary to a great extent (4-26 ms) from one neuron to another, and (3) high
      threshold hyperpolarization preceded long latency spikes in IC neurons exhibiting
      paradoxical latency shift. Our data also show that the onset hyperpolarizing
      potentials in the IC have very small jitter (<100 micros) across repeated
      stimulus presentations. The results of this study suggest that inhibition,
      arriving earlier than excitation, may play a role as a mechanism for delaying the
      first spike latency in IC neurons.

PMID- 18621104
TI  - Ketamine inhibits long-term, but not intermediate-term memory formation in
      Lymnaea stagnalis.
AB  - We investigated the effects of the drug ketamine on procedural intermediate- and
      long-term memory formation in a well-established operant learning and memory
      model system, Lymnaea stagnalis. Animals were administered ketamine at discrete
      time points, ranging from 2 h pre-one-trial training (1TT) to 23 h post-1TT. Our
      results demonstrated that ketamine causes impairment of procedural memory
      formation, and that ketamine acts differentially, inhibiting only long-term
      memory (LTM) formation while having no effect on intermediate-term memory (ITM)
      formation. Ketamine's ability to inhibit LTM was found not to be due to state
      dependent learning implying that ketamine's effects are therefore specific to the
      molecular process involved in procedural LTM formation. Given past data from our
      laboratory, this suggests that ketamine may be exerting its differential effects
      by altering the gene transcription processes necessary and specific for LTM
      formation. Additionally, ketamine was found to have no effect on retrieval when
      administered 1 h before testing. However, ketamine was able to disrupt LTM
      formation when administered immediately before 1TT and up to 2 h after 1TT. Our
      findings suggest a longer period of consolidation after 1TT than previously
      demonstrated in Lymnaea, during which the procedural long-term memory remains
      labile and is vulnerable to disruption via amnestic agents, such as ketamine.

PMID- 18621103
TI  - Inflammatory pain-induced signaling events following a conditional deletion of
      the N-methyl-D-aspartate receptor in spinal cord dorsal horn.
AB  - The N-methyl-d-aspartate (NMDA) receptor in the spinal cord dorsal horn (SCDH) is
      one of the mechanisms involved in central sensitization during chronic pain.
      Previously, this laboratory created a spatio-temporal knockout (KO) of the N
      methyl-d-aspartate receptor I (NR1) subunit in the mouse SCDH. The NR1 KO
      completely blocks NR1 gene and subsequent NMDA receptor expression and function
      in SCDH neurons. In the NR1 KO mice, the mechanical and cold allodynia induced at
      24 h after complete Freund's adjuvant (CFA) was reduced. However, the protective
      effects of KO were transient and were not seen at 48 h after CFA. These
      observations suggest the presence of NMDA-independent pathways that contribute to
      CFA-induced pain. CFA induces the activation of several signaling cascades in the
      SCDH, including protein kinase C (PKC)gamma and extracellular signal-regulated
      kinases (ERK1/2). The phosphorylation of PKCgamma and ERK1/2 was inhibited in the
      SCDH of NR1 KO mice up to 48 h after CFA treatment, suggesting that these
      pathways are NMDA receptor-dependent. Interestingly, neuronal cyclooxygenase
      (COX) -2 expression and microglial p38 phosphorylation were induced in the SCDH
      of the NR1 KO at 48 h after CFA. Our findings provide evidence that inflammatory
      reactions are responsible for the recurrence of pain after NR1 KO in the SCDH.

PMID- 18621105
TI  - Age-related changes in polyamines in memory-associated brain structures in rats.
AB  - Polyamines putrescine, spermidine and spermine are positively charged aliphatic
      amines and have important roles in maintaining normal cellular function,
      regulating neurotransmitter receptors and modulating learning and memory. Recent
      evidence suggests a role of putrescine in hippocampal neurogenesis, that is
      significantly impaired during aging. The present study measured the polyamine
      levels in memory-related brain structures in 24- (aged), 12- (middle-aged) and 4-
      (young) month-old rats using liquid chromatography/mass spectrometry and high
      performance liquid chromatography. In the hippocampus, the putrescine levels were
      significantly decreased in the CA1 and dentate gyrus, and increased in the CA2/3
      with age. Significant age-related increases in the spermidine levels were found
      in the CA1 and CA2/3. There was no difference between groups in spermine in any
      sub-regions examined. In the parahippocampal region, increased putrescine level
      with age was observed in the entorhinal cortex, and age did not alter the
      spermidine levels. The spermine level was significantly decreased in the
      perirhinal cortex and increased in the postrhinal cortex with age. In the
      prefrontal cortex, there was age-related decrease in putrescine, and the
      spermidine and spermine levels were significantly increased with age. This study,
      for the first time, demonstrates age-related region-specific changes in
      polyamines in memory-associated structures, suggesting that polyamine system
      dysfunction may potentially contribute to aged-related impairments in hippocampal
      neurogenesis and learning and memory.

PMID- 18621106
TI  - Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1
      42: involvement of endoplasmic reticulum calcium release in oligomer-induced cell
      death.
AB  - The nature of the toxic form of amyloid-beta peptide (Abeta) involved in early
      Alzheimer's disease (AD) pathology and whether it is the fibrillar or the
      oligomeric peptide that is the most deleterious to neurons remain controversial.
      This work aimed to compare the neurotoxicity of different amyloid-beta peptide 1
      42 (Abeta1-42) assemblies, using fresh and aged samples enriched in oligomeric
      and fibrillar species, respectively, and also isolated oligomers and fibrils. The
      results obtained with fresh and aged Abeta1-42 preparations suggested that
      oligomeric species are more toxic to cortical neurons in culture than fibrillar
      forms, which was confirmed by using isolated oligomers and fibrils. In order to
      further elucidate the mechanisms involved in soluble Abeta toxicity, the
      involvement of endoplasmic reticulum (ER) calcium (Ca(2+)) release in oligomer
      induced apoptosis was evaluated. We observed that oligomeric Abeta1-42 depletes
      ER Ca(2+) levels leading to intracellular Ca(2+) dyshomeostasis involving
      phospholipase C activation. Moreover, in the presence of dantrolene, an inhibitor
      of ER Ca(2+) release through ryanodine receptors, the oligomer-induced apoptosis
      was prevented demonstrating the involvement of ER Ca(2+) release.

PMID- 18621107
TI  - Involvement of angiotensin converting enzyme in cerebral hypoperfusion induced
      anterograde memory impairment and cholinergic dysfunction in rats.
AB  - Forebrain cholinergic dysfunction is the hallmark of vascular dementia (VaD) and
      Alzheimer's dementia (AD) induced by cerebral hypoperfusion during aging. The aim
      of the present study is to evaluate the role of angiotensin converting enzyme
      (ACE) in cerebral hypoperfusion-induced dementia and cholinergic dysfunction.
      Chronic cerebral hypoperfusion (CHP) was induced by permanent bilateral common
      carotid artery (2VO) occlusion in rats. Chronic cerebral hypoperfusion resulted
      in anterograde memory impairment revealed from Morris water maze (MWM) and
      passive avoidance step through tasks (PA), which was significantly attenuated by
      ACE inhibitor, captopril. Cerebral hypoperfusion down-regulated the relative
      expression of cholinergic muscarinic receptor (ChM-1r) and choline
      acetyltransferase (ChAT) as well as up-regulated the angiotensin II type-1
      receptor (AT-1) expression in hippocampus of vehicle treated CHP group on the
      54th day post-hypoperfusion. The diminished number of presynaptic cholinergic
      neurons and the pyramidal neurons were evident from ChAT-immunofluorescence and
      the hematoxylin and eosin (H&E) staining studies respectively in hippocampal
      Cornu ammonis1 (CA1); region of vehicle-treated hypoperfused animals. Further the
      lipid peroxidation level was also found to be elevated in the hippocampus of the
      vehicle-treated group. Our results demonstrated that continuous captopril
      treatment (50 mg/kg, i.p. twice daily) for 15 days mitigated the hypoperfusion
      induced cholinergic hypofunction and neurodegeneration in hippocampus. The
      present study robustly reveals that the angiotensinergic system plays a pivotal
      role in progression of neuronal death and memory dysfunctions during cerebral
      hypoperfusion.

PMID- 18621109
TI  - Differential activity to shapes under shape-from-motion condition in macaque
      middle temporal area.
AB  - To investigate the neural mechanisms of motion-defined shape processing, we
      recorded single unit activity in the middle temporal area (MT) while monkeys
      performed a shape discrimination task under the shape-from-motion (SFM)
      condition, where a motion cue is critical for shape perception. About 40% of MT
      neurons responded differentially to shapes under the SFM condition. The
      differential responses to shapes could not be explained by either the
      heterogeneous structure of the receptive field or the amount of motion signal. On
      the other hand, under the shape-from-luminance (SFL) condition, where a luminance
      cue is critical for shape perception, the proportion of neurons showing
      differential responses to shapes was smaller than that under the SFM condition
      and the magnitudes of differential responses themselves were weaker. Thus, the
      requirement for motion processing for shape perception may facilitate a
      differential response to shapes under the SFM condition. We compared neuronal
      activities during the shape discrimination task with those during the direction
      discrimination task under the SFM condition. Differential responses to shapes
      were observed more frequently during the shape discrimination task than during
      the direction discrimination task. Thus, the motion-defined shape processing
      influenced MT activity.

PMID- 18621110
TI  - Antiulcer activity of water extract of Scoparia dulcis.
AB  - Oral treatment with the water extracts of Scoparia dulcis whole aerial parts, at
      doses of 50, 100 and 200 mg/kg, dose dependently inhibited the indomethacin
      induced gastric damages in rats.

PMID- 18621108
TI  - Diverse roles of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in neuroinflammation and cerebral ischemia.
AB  - Regulation of the extracellular matrix by proteases and protease inhibitors is a
      fundamental biological process for normal growth, development and repair in the
      CNS. Matrix metalloproteinases (MMPs) and the tissue inhibitors of
      metalloproteinases (TIMPs) are the major extracellular-degrading enzymes. Two
      other enzyme families, a disintegrin and metalloproteinase (ADAM), and the serine
      proteases, plasminogen/plasminogen activator (P/PA) system, are also involved in
      extracellular matrix degradation. Normally, the highly integrated action of these
      enzyme families remodels all of the components of the matrix and performs
      essential functions at the cell surface involved in signaling, cell survival, and
      cell death. During the inflammatory response induced in infection, autoimmune
      reactions and hypoxia/ischemia, abnormal expression and activation of these
      proteases lead to breakdown of the extracellular matrix, resulting in the opening
      of the blood-brain barrier (BBB), preventing normal cell signaling, and
      eventually leading to cell death. There are several key MMPs and ADAMs that have
      been implicated in neuroinflammation: gelatinases A and B (MMP-2 and -9),
      stromelysin-1 (MMP-3), membrane-type MMP (MT1-MMP or MMP-14), and tumor necrosis
      factor-alpha converting enzyme (TACE). In addition, TIMP-3, which is bound to the
      cell surface, promotes cell death and impedes angiogenesis. Inhibitors of
      metalloproteinases are available, but balancing the beneficial and detrimental
      effects of these agents remains a challenge.

PMID- 18621111
TI  - Estrogenic activity of the dichloromethane extract from Pueraria mirifica.
AB  - Pueraria mirifica and its extracts are widely used as the ingredient(s) in many
      rejuvenating products. Up to now, the extract of P. mirifica roots that has been
      used in most studies, is the alcoholic extract. In the present study, we
      investigated the estrogenic activity using uterotropic and MCF-7 cell
      proliferation models of the dichloromethane extract as well as the water extract
      which was obtained from partitioning the ethanolic extract. The results indicated
      that among the three extracts, i.e. the ethanolic extract (PM1), the water
      extract (PM2) and dichloromethane extract (PM3), PM3 exhibited the most potent
      estrogenic activity in both models, followed by PM1. The extracts produced
      uterotropic activity associated with the increase of water content while
      uterotropic activity of 17beta-estradiol was related to the increase of muscle
      mass. The two isoflavonoids, genistein and daidzein, were not the major active
      phytoestrogens involving the estrogenic activity of these extracts.

PMID- 18621112
TI  - Early induction of LDL receptor gene expression by genistein in DLD-1 colon
      cancer cell line.
AB  - The phytoestrogen genistein has been demonstrated to possess anti-tumor
      properties by mechanisms not yet clearly established. The present study was
      designed to investigate the effects of isoflavone genistein exposure at
      concentrations ranging from 0.01 microM to 50 microM on the LDL receptor and
      HMGCoA reductase gene expression in the estrogen receptor positive DLD-1 human
      colon cancer cell line. LDL receptor and HMGCoA reductase gene expressions were
      evaluated by reverse transcription followed by real-time PCR. Genistein induced
      an early increase of LDL receptor gene expression and later decreased HMGCoA
      reductase mRNA expression in DLD-1 cells. These findings provide direct evidence
      on the role of genistein in regulating LDL receptor and HMGCoA reductase gene
      expression in colon cancer.

PMID- 18621113
TI  - Antimicrobial anthraquinones from Morinda angustifolia.
AB  - Investigation on Morinda angustifolia resulted in the isolation of a new
      anthraquinone, 1,8-dihydroxy-2-methyl-3,7-dimethoxyanthraquinone (1), along with
      five known analogues, lucidin 3-O-beta-primeveroside (2), 1,3-dihydroxy-2
      methylanthraquinone (3), lucidin- omega -ethyl ether (4), lucidin-omega-butyl
      ether (5) and damnacanthol (6). The new compound demonstrated significant
      antimicrobial activity against Bacillus subtilis, Escherichia coli, Micrococcus
      luteus, Sarcina lutea, Candida albicans and Saccharomyces sake.

PMID- 18621114
TI  - Hepatoprotective activity of Vitex negundo leaf extract against anti-tubercular
      drugs induced hepatotoxicity.
AB  - Hepatoprotective (HP) activity of Vitex negundo (VN) leaf ethanolic extract was
      investigated against hepatotoxicity (HT) produced by administering a combination
      of three anti-tubercular drugs isoniazid (INH)-7.5 mg/kg, rifampin (RMP)-10 mg/kg
      and pyrazinamide (PZA)-35 mg/kg for 35 35 days by oral route in rats. V. negundo
      leaf ethanolic extract was administered in three graded doses of 100, 250 and 500
      mg/kg orally, 45 min prior to anti-tubercular challenge for 35 days. HP effect of
      V. negundo leaf ethanolic extract was evident in the doses of 250 and 500 mg/kg
      as there was a significant decrease in TB, AST, ALT and ALP levels in comparison
      to control. Histology of the liver section of the animals treated with the V.
      negundo leaf ethanolic extract in the doses of 250 and 500 mg/kg further confirms
      the HP activity.

PMID- 18621115
TI  - Antimicrobial and cytotoxic activities of Laportea crenulata.
AB  - Crude extracts and 2alpha,3beta,21beta,24beta,28-pentahydroxy-olean-12-ene (1)
      obtained from the root of Laportea crenulata exhibited remarkable antibacterial
      activities against both Gram (+) and Gram (-) bacteria. The antifungal activities
      of crude extracts and compound (1) were also determined. The cytotoxic activities
      of crude extracts and compound (1) were observed by brine shrimp bioassay and
      LC(50) value of the compound (1) was found to be 27.54 microg/ml.

PMID- 18621116
TI  - Vectors for enhanced gene expression and protein purification in Salmonella.
AB  - Improved expression vectors have been tested for protein expression studies in
      Salmonella spp. They are derived from the broad host range expression vector
      pNSGroE [Seleem, M.N., Vemulapalli, R., Boyle, S.M., Schurig, G.G. and
      Sriranganathan, N., 2004. Improved expression vector for Brucella species.
      Biotechniques 37, 740-744] and have several advantages (i) small in size (less
      than 3 kb); (ii) possess eleven unique restriction site to facilitate directional
      cloning; (iii) express proteins as His-tagged fusions for easy detection and
      purification; (iv) carry different promoters for various level of expression and
      (v) carry an UP element and RNA stem-loop for enhanced gene expression. We have
      demonstrated the ability of the new vectors to stably express heterologous
      proteins in Salmonella. We also demonstrated the utility of our vectors by
      detecting expression and purification of recombinant GFP. Our results suggest
      that these new vectors should improve gene expression in Salmonella, particularly
      those aimed at foreign antigen delivery.

PMID- 18621117
TI  - On the relationship between perfect matches and mismatches in Affymetrix
      Genechips.
AB  - A relationship which links the fluorescence intensity histograms for perfect
      match (PM) and mismatch (MM) probes in Affymetrix Genechips is derived using
      inputs from physical-chemistry as the Langmuir and the Nearest Neighbor models.
      This relationship is in good agreement with experimental data from few dozens of
      chips belonging to about 10 different organisms. Principles of physical-chemistry
      impose some constant value for the average ratios of PM and MM intensities.
      Experimental data, however, show quite some variations in these parameters,
      although they follow the same inequalities as expected from hybridization free
      energies for oligonucleotides melting in solution. It is suggested that the
      anomalous experiment to experiment differences are due to 1) problems with chip
      design and 2) excessive fragmentation of the target in solution. The histogram
      analysis developed may be a useful preprocessing step to evaluate the global
      quality of the experimental data, prior to the calculation of the gene expression
      level.

PMID- 18621118
TI  - How does gene expression level contribute to thermophilic adaptation of
      prokaryotes? An exploration based on predictors.
AB  - By analyzing the predicted gene expression levels of 33 prokaryotes with living
      temperature span from <10 degrees C to >100 degrees C, a universal positive
      correlation was found between the percentage of predicted highly expressed genes
      and the organisms' optimal growth temperature. A physical interpretation of the
      correlation revealed that highly expressed genes are statistically more
      thermostable than lowly expressed genes. These findings show the possibility of
      the significant contribution of gene expression level to the prokaryotic thermal
      adaptation and provide evidence for the translational selection pressure on the
      thermostability of natural proteins during evolution.

PMID- 18621119
TI  - Effects of alkylphenols on bone metabolism in vivo and in vitro.
AB  - Alkylphenols are endocrine disruptors that show estrogen-like effects in various
      wildlife species. However, little information is available about the action of
      these chemicals on bone metabolism. We investigated the effects of alkylphenols,
      such as nonylphenol (NP) and octylphenol (OP), on the formation of bone using
      several culture systems for osteoclasts and osteoblasts, as well as in vivo
      experiments. NP and OP dose-dependently inhibited the formation of tartrate
      resistant acid phosphatase-positive multinucleated cells (osteoclasts) in
      cocultures of mouse spleen cells or mouse bone marrow cells with ST2 cells.
      However, beta-estradiol at 10(-9)M to 10(-6)M did not affect this process. In
      contrast, neither compound affected the proliferation and differentiation of rat
      calvarial osteoblast-like cells (ROB cells). When NP or OP (0.1mg/kg body weight)
      was administered subcutaneously to pregnant mice at 10 days, 12 days and 14 days
      post-coitus, fetuses at 17.5 days post-coitus showed stimulation of sternebrae
      bone calcification. Our findings suggest that alkylphenols have critical effects
      on the formation of bone by non-estrogenic effects.

PMID- 18621120
TI  - Evaluating particle hardness of pharmaceutical solids using AFM nanoindentation.
AB  - Understanding mechanical properties of pharmaceutical solids at the submicron
      scale can be very important to pharmaceutical research & development. In this
      paper, the hardness of individual particles of various pharmaceutical solids
      including sucrose, lactose, ascorbic acid, and ibuprofen was quantified using the
      atomic force microscopy (AFM) nanoindentation. Effects of data variation and
      indentation size or peak load on hardness are evaluated. The results show
      acceptable reproducibility and indicate that data variation may be primarily from
      the inhomogeneous nature of the samples. Different extents of indentation size or
      peak load effect on hardness were observed for the samples. With consideration of
      both data variation and indentation size effects, the hardness values of
      different samples were compared at similar contact depths or peak loads. The
      hardness ranked as: ascorbic acid>sucrose>lactose approximately ibuprofen, at
      contact depths from approximately 40 to 400 nm or peak loads ranging from
      approximately 16 to 70 microN. Additionally, the potential implication of
      particle hardness to compact hardness and tableting performance was discussed.

PMID- 18621121
TI  - South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia
      phylicoides--a review.
AB  - Rooibos (Aspalathus linearis (Brum.f) Dahlg.) and honeybush (Cyclopia Vent.
      species) are popular indigenous South African herbal teas enjoyed for their taste
      and aroma. Traditional medicinal uses of rooibos in South Africa include
      alleviation of infantile colic, allergies, asthma and dermatological problems,
      while a decoction of honeybush was used as a restorative and as an expectorant in
      chronic catarrh and pulmonary tuberculosis. Traditional medicinal uses of
      Athrixia phylicoides DC., or bush tea, another indigenous South African plant
      with very limited localised use as herbal tea, include treatment of boils, acne,
      infected wounds and infected throats. Currently rooibos and honeybush are
      produced for the herbal tea market, while bush tea has potential for
      commercialisation. A summary of the historical and modern uses, botany,
      distribution, industry and chemical composition of these herbal teas is
      presented. A comprehensive discussion of in vitro, ex vivo and in vivo biological
      properties, required to expand their applications as nutraceutical and
      cosmeceutical products, is included, with the main emphasis on rooibos. Future
      research needs include more comprehensive chemical characterisation of extracts,
      identification of marker compounds for extract standardisation and quality
      control, bioavailability and identification of bio-markers of dietary exposure,
      investigation of possible herb-drug interactions and plant improvement with
      regards to composition and bioactivity.

PMID- 18621122
TI  - Peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) assay for
      specific detection of Mycobacterium immunogenum and DNA-FISH assay for analysis
      of pseudomonads in metalworking fluids and sputum.
AB  - Specific and rapid detection and quantification of mycobacteria in contaminated
      metalworking fluid (MWF) are problematic due to complexity of the matrix and
      heavy background co-occurring microflora. Furthermore, cross-reactivity among
      neighboring species of Mycobacterium makes species differentiation difficult for
      this genus. Here, we report for the first time a species-specific peptide nucleic
      acid-fluorescence in situ hybridization (PNA-FISH) method for Mycobacterium
      immunogenum, a non-tuberculous Mycobacterium species prevalent in MWF and
      implicated in occupational lung disease hypersensitivity pneumonitis and pseudo
      outbreaks. A novel species-specific 14-bp PNA probe was designed for M.
      immunogenum based on its 16S rRNA gene sequence and was validated for
      specificity, by testing against a panel of other phylogenetically closely related
      rapidly growing mycobacteria and representative species of gram-positive, gram
      negative, and acid fast organisms. In addition, a DNA-FISH protocol was optimized
      for co-detection of Pseudomonas, the most predominantly co-occurring genus in
      contaminated MWF. Reliable quantification for both the test organisms was
      achieved at or above a cell density of 10(3)cellsml(-1), a recognized minimum
      limit for microscopic quantification. The mycobacterial PNA-FISH assay was
      successfully adapted to human sputum demonstrating its potential for clinical
      diagnostic applications in addition to industrial MWF monitoring, to assess MWF
      associated exposures and pseudo-outbreaks.

PMID- 18621124
TI  - The immense journey of bacteriophage T4--from d'Herelle to Delbruck and then to
      Darwin and beyond.
AB  - In spite of their importance, the genomics, diversity and evolution of phages and
      their impact on the biosphere have remained largely unexplored research domains
      in microbiology. Here, we report on some recent studies with the T4 phage
      superfamily that shed some new light on these topics.

PMID- 18621123
TI  - As(III) inhibits ultraviolet radiation-induced cyclobutane pyrimidine dimer
      repair via generation of nitric oxide in human keratinocytes.
AB  - Inorganic arsenic enhances skin tumor formation when combined with other
      carcinogens including ultraviolet radiation (UVR). The inhibition of DNA damage
      repair by arsenic has been hypothesized to contribute to the cocarcinogenic
      activities of arsenic observed in vivo. Cyclobutane pyrimidine dimers (CPDs) are
      an important mutagenic UVR photoproduct and implicated in the genesis of
      nonmelanoma skin cancer. The current study demonstrates that low concentrations
      of arsenite (As(III)) inhibit UVR-induced CPD repair in a human keratinocyte cell
      line via nitric oxide (NO) and inducible nitric oxide synthase (iNOS). Following
      As(III) treatment, NO production and iNOS expression are elevated. Little is
      known about regulation of iNOS by As(III) and further investigations indicated
      that p38 mitogen-activated protein kinase (p38 MAPK) and NF-kappaB are required
      for As(III) induction of iNOS expression. This As(III)-stimulated signaling
      cascade was involved in inhibition of UVR-induced CPD repair as disruption of p38
      MAPK activity and NF-kappaB nuclear translocation counteracted the effects of
      As(III) on CPD repair. Selective inhibition of iNOS ameliorated As(III)
      inhibition of CPD repair, thereby suggesting that iNOS is a downstream mediator
      of As(III) activity. These findings provide evidence that an As(III)-stimulated
      signal transduction cascade culminating in elevated iNOS expression and NO
      generation is an underlying mechanism for inhibition of UVR-induced DNA damage
      repair by arsenic.

PMID- 18621125
TI  - Transport of amino acids and GABA analogues via the human proton-coupled amino
      acid transporter, hPAT1: characterization of conditions for affinity and
      transport experiments in Caco-2 cells.
AB  - The objective of this study was to investigate transepithelial amino acid
      transport as a function of Caco-2 cell culture time. Furthermore, the objective
      was to investigate apical uptake characteristics of hPAT1-mediated transport
      under various experimental conditions. Apical amino acid uptake and transport
      studies were conducted in Caco-2 monolayers cultured for 4-28 days.
      Transepithelial transport of the prototypic hPAT1 (SLC36A1) substrates l-proline
      and glycine were maximal after 21-28 days in culture. Based on proton-dependency
      and substrate kinetics the major apical uptake and transport of Gly and Pro in
      Caco-2 cell monolayers is hPAT1-mediated. The apical uptake of Pro is decreased
      at apical hyperosmolarity conditions. Furthermore we identified the two GABA
      analogues, muscimol and THPO as novel hPAT1 substrates. THPO had an affinity for
      hPAT1 of 11.3mM, whereas muscimol had one of the highest affinities for hPAT1
      (1.7mM) reported. Our findings illustrate the suitability of the Caco-2 model for
      studying hPAT1-mediated transport. Furthermore, the affinity of THPO and muscimol
      underlines the possible importance of hPAT1 as a transporter for heterocyclic
      compounds consisting of a 3-isoxazolol moiety, which has been shown to function
      as a carboxylic acid bioisostere for substrates of the GABA receptor and
      transport systems.

PMID- 18621126
TI  - Integrins as regulators of the mitotic machinery.
AB  - Mitotic spindle bipolarity defines a unique division plane that promotes the
      successful transmission of genetic material during cytokinesis. The positioning
      and orientation of the spindle determines the symmetry of cell division and the
      relative location of daughter cells, which regulate cell fate decisions that
      contribute to embryonic development and tissue differentiation. Recent studies
      have identified integrins as regulators of spindle positioning and orientation,
      as well as spindle bipolarity and cytokinesis. This review summarizes and
      discusses the current effort focused on understanding how integrins regulate
      these mitotic events.

PMID- 18621127
TI  - Anti-obesity, anti-diabetic, and lipid lowering effects of the thyroid receptor
      beta subtype selective agonist KB-141.
AB  - Selective thyroid hormone receptor subtype-beta (TRbeta) agonists have received
      attention as potential treatments for hypercholesterolemia and obesity, but have
      received less attention as treatments for diabetes, partly because this condition
      is not improved in thyroid hormone excess states. The TRbeta selective agonist KB
      141 induces 5-10% increases in metabolic rate and lowering of plasma cholesterol
      levels without tachycardia in lean rats, unlike the major active thyroid hormone,
      T3. In the current study, we determined whether KB-141 promotes weight loss in
      obese animals and whether it exhibits anti-diabetogenic effects. Body weight,
      adiposity (DEXA), and lipid levels were examined following p.o. administration of
      KB-141 to obese Zucker fa/fa rats at 0.00547-0.547 mg/kg/day for 21 days, and in
      ob/ob mice at 0.5mg/kg/day KB-141 for 7 days. In rats, KB-141 reduced body weight
      by 6 and 8%, respectively, at 0.167 and 0.0547 mg/kg/day without tachycardia and
      adiposity was reduced at 0.167 mg/kg/day (5-6%). In ob/ob mice, KB-141 lowered
      serum cholesterol (35%), triacylglycerols (35%) and both serum and hepatic free
      fatty acids (18-20%) without tachycardia. Treatment of ob/ob mice with KB-141
      (0.0547 or 0.328 mg/kg/day over 2 weeks) improved glucose tolerance and insulin
      sensitivity in a dose-dependent manner with no effect on heart rate. Thus, KB-141
      elicits anti-obesity, lipid lowering and anti-diabetic effects without
      tachycardia suggesting that selective TRbeta activation may be useful strategy to
      attenuate features of the metabolic syndrome.

PMID- 18621128
TI  - Regional changes in the spatio-temporal pattern of progesterone receptor (PR)
      expression in the guinea-pig genital tract as parturition approaches.
AB  - Normal parturition in guinea-pig involves changes in responsiveness of the
      genital tract to estrogen and progesterone. To better characterize endocrine
      control of guinea-pig parturition, protein and mRNA expression of estrogen
      receptor-alpha (ERalpha) and progesterone receptor (PR) were quantitatively
      evaluated in lower (LUS) and upper (UUS) uterine segments, cervix (C) and pubic
      symphyseal ligament (PSL) at three stages of pregnancy (established based on
      interpubic distance, 0mm: non-relaxed group, 4-6mm: 5 days before parturition, 11
      14 mm: 1-2 days prepartum) and immediately after parturition. Towards
      parturition, no changes in PR mRNA levels were recorded in the UUS, whereas the
      LUS displayed a gradual increase. PR transcripts exhibited decreased levels
      during parturition in C and PSL. Levels of PR mRNA were increased in the LUS
      compared with that of the UUS only at parturition. Regarding protein expression
      during parturition, PR levels decreased in the UUS whereas in the LUS increased.
      In C and PSL, PR protein expression decreased 1-2 days prepartum and remained low
      during parturition. None of the regions studied showed changes in mRNA or protein
      expression of ERalpha. Therefore, functional regionalization of the guinea-pig
      genital tract is associated with changes in the spatio-temporal pattern of PR
      expression as parturition approaches.

PMID- 18621129
TI  - Human prostate stromal cells stimulate increased PSA production in DHEA-treated
      prostate cancer epithelial cells.
AB  - Dehydroepiandrosterone (DHEA) is commonly used as a dietary supplement and may
      affect prostate pathophysiology when metabolized to androgens and/or estrogens.
      Human prostate LAPC-4 cancer cells with a wild type androgen receptor (AR) were
      treated with DHEA, androgens dihydrotestosterone (DHT), T, or R1881), and E2 and
      assayed for prostate specific antigen (PSA) protein and gene expression. In LAPC
      4 monocultures, DHEA and E2 induced little or no increase in PSA protein or mRNA
      expression compared to androgen-treated cells. When prostate cancer-associated
      (6S) stromal cells were added in coculture, DHEA stimulated LAPC-4 cell PSA
      protein secretion to levels approaching induction by DHT. Also, DHEA induced 15
      fold more PSA mRNA in LAPC-4 cocultures than in monocultures. LAPC-4
      proliferation was increased 2-3-fold when cocultured with 6S stromal cells
      regardless of hormone treatment. DHEA-treated 6S stromal cells exhibited a dose-
      and time-dependent increase in T secretion, demonstrating stromal cell metabolism
      of DHEA to T. Coculture with non-cancerous stroma did not induce LAPC-4 PSA
      production, suggesting a differential modulation of DHEA effect in a cancer
      associated prostate stromal environment. This coculture model provides a research
      approach to reveal detailed endocrine, intracrine, and paracrine signaling
      between stromal and epithelial cells that regulate tissue homeostasis within the
      prostate, and the role of the tumor microenvironment in cancer progression.

PMID- 18621130
TI  - Nav1.1 is predominantly expressed in nodes of Ranvier and axon initial segments.
AB  - Aggregation of voltage-gated sodium (Nav) channels in the axon initial segment
      (AIS) and nodes of Ranvier is essential for the generation and propagation of
      action potentials. From the three Nav channel isoforms (Nav1.1, Nav1.2 and
      Nav1.6) expressed in the adult CNS, Nav1.1 appears to play an important function
      since numerous mutations in its coding sequence cause epileptic syndromes. Yet,
      its distribution is still controversial. Here we demonstrate for the first time
      that in the adult CNS Nav1.1 is expressed in nodes of Ranvier throughout the
      mouse spinal cord and in many brain regions. We identified three populations of
      nodes: expressing Nav1.1, Nav1.6 or both. We also found Nav1.1 expression
      concentrated in a proximal AIS subcompartment in spinal cord neurons including
      80% of motor neurons and in multiple brain areas. This novel distribution
      suggests that Nav1.1 is involved in the control of action potential generation
      and propagation.

PMID- 18621131
TI  - A tractography comparison between turboprop and spin-echo echo-planar diffusion
      tensor imaging.
AB  - The development of accurate, non-invasive methods for mapping white matter fiber
      tracts is of critical importance. However, fiber-tracking is typically performed
      on diffusion tensor imaging (DTI) data obtained with echo-planar-based imaging
      techniques (EPI), which suffer from susceptibility-related image artifacts, and
      image warping due to eddy-currents. Thus, a number of white matter fiber-bundles
      mapped using EPI-based DTI data are distorted and/or terminated early. This
      severely limits the clinical potential of fiber-tracking. In contrast, Turboprop
      MRI provides images with significantly fewer susceptibility and eddy-current
      related artifacts than EPI. The purpose of this work was to compare fiber
      tracking results obtained from DTI data acquired with Turboprop-DTI and EPI-based
      DTI. It was shown that, in brain regions near magnetic field inhomogeneities,
      white matter fiber-bundles obtained with EPI-based DTI were distorted and/or
      partially detected, when magnetic susceptibility-induced distortions were not
      corrected. After correction, residual distortions were still present and several
      fiber-tracts remained partially detected. In contrast, when using Turboprop-DTI
      data, all traced fiber-tracts were in agreement with known anatomy. The inter
      session reproducibility of tractography results was higher for Turboprop than EPI
      based DTI data in regions near field inhomogeneities. Thus, Turboprop may be a
      more appropriate DTI data acquisition technique for tracing white matter fibers
      near regions with significant magnetic susceptibility differences, as well as in
      longitudinal studies of such fibers. However, the intra-session reproducibility
      of tractography results was higher for EPI-based than Turboprop DTI data. Thus,
      EPI-based DTI may be more advantageous for tracing fibers minimally affected by
      field inhomogeneities.

PMID- 18621132
TI  - Potential gene flow in natural populations of the Drosophila ananassae species
      cluster inferred from a nuclear mitochondrial pseudogene.
AB  - A pseudogene with 94% similarity to mitochondrial cytochrome c oxidase subunit I
      (COI) was identified and localized to chromosome 4 of Drosophila ananassae.
      Because this chromosome is believed to have reduced recombination, its history
      can be traced using the pseudo-COI sequence. Pseudo-COI sequences were obtained
      from 27 iso-female lines of six taxa belonging to the D. ananassae species
      cluster in which reproductive isolation is incomplete. The phylogenetic network
      constructed from seven recognized haplotypes (#0-#6) indicated that different
      taxa inhabiting the same geographic area share the haplotypes: #1 from Papua New
      Guinean populations of D. ananassae and pallidosa-like-Wau; #2 from Papua New
      Guinean populations of D. ananassae, pallidosa-like, and papuensis-like; and #4
      from South Pacific populations of D. ananassae and D. pallidosa. Taxon-K has a
      unique haplotype (#6), and 18 mutation steps separate it from the closest
      haplotype, #2. We discuss the possibility of chromosome 4 introgression beyond
      taxon boundaries.

PMID- 18621134
TI  - Challenging the problem of clostridial identification with matrix-assisted laser
      desorption and ionization-time-of-flight mass spectrometry (MALDI-TOF MS).
AB  - Diverse techniques were applied to effect the identification and classification
      of isolated clostridial strains. Nevertheless, the correct identification of
      clostridial strains remains a laborious, time-consuming task which entails a not
      inconsiderable degree of expertise. In addition to this, traditional methods
      based on the metabolic properties of the bacteria require rigorously standardized
      media and growth conditions to assure the attainment of reproducible results.
      Although DNA-based methods, like the PCR of a species specific gene, are known to
      yield precise and reproducible results, their degree of effectivity is
      circumscribed by the fact that even the incidence of a toxin encoding gene is not
      necessarily linked to nor consequently indicative of the presence of an
      infectious disease. Moreover, most of these methods postulate an initial
      assumption concerning the expected bacterial species involved before the choice
      of PCR primer for use can be made. Consequently, the scope of these methods is
      restricted to that of targeted analyses. The 16S rDNA sequencing which is assumed
      to be the gold standard for bacterial classification having the unequivocal
      advantage of being capable of determining even uncultivable bacteria is
      nonetheless a time-consuming and costly technique. In the present study we
      describe the utilization of matrix-assisted laser desorption and ionization-time
      of-flight mass spectrometry (MALDI-TOF MS) for whole cell fingerprinting in
      combination with a dedicated bioinformatic software tool to distinguish between
      various clostridial species. Total 64 clostridial strains of 31 different species
      each displayed a mass spectrum unique to the strain involved, to the effect that
      it was also possible not only to differentiate between the strains examined, but
      also to establish to which species the individual strains belonged to. Starting
      with a single colony it was possible to correctly identify a Clostridium species
      within minutes. It was even possible to identify species which are normally
      difficult to differentiate by traditional methods, such as C. chauvoei and C.
      septicum. With the results obtained we were able to assemble a dendrogram of the
      Clostridium species which showed considerable similarities to dendrograms based
      upon 16S rDNA sequencing data. To conclude, our findings indicate that, inasmuch
      as the MALDI-TOF MS technology employed is based on a high-quality reference
      database, it may serve as an effective tool for the swift and reliable
      identification and classification of Clostridia.

PMID- 18621133
TI  - Phylogenetic relationships and the evolution of regulatory gene sequences in the
      parrotfishes.
AB  - Regulatory genes control the expression of other genes and are key components of
      developmental processes such as segmentation and embryonic construction of the
      skull in vertebrates. Here we examine the variability and evolution of three
      vertebrate regulatory genes, addressing issues of their utility for phylogenetics
      and comparing the rates of genetic change seen in regulatory loci to the rates
      seen in other genes in the parrotfishes. The parrotfishes are a diverse group of
      colorful fishes from coral reefs and seagrasses worldwide and have been placed
      phylogenetically within the family Labridae. We tested phylogenetic hypotheses
      among the parrotfishes, with a focus on the genera Chlorurus and Scarus, by
      analyzing eight gene fragments for 42 parrotfishes and eight outgroup species. We
      sequenced mitochondrial 12s rRNA (967 bp), 16s rRNA (577 bp), and cytochrome b
      (477 bp). From the nuclear genome, we sequenced part of the protein-coding genes
      rag2 (715 bp), tmo4c4 (485 bp), and the developmental regulatory genes otx1 (672
      bp), bmp4 (488bp), and dlx2 (522 bp). Bayesian, likelihood, and parsimony
      analyses of the resulting 4903 bp of DNA sequence produced similar topologies
      that confirm the monophyly of the scarines and provide a phylogeny at the species
      level for portions of the genera Scarus and Chlorurus. Four major clades of
      Scarus were recovered, with three distributed in the Indo-Pacific and one
      containing Caribbean/Atlantic taxa. Molecular rates suggest a Miocene origin of
      the parrotfishes (22 mya) and a recent divergence of species within Scarus and
      Chlorurus, within the past 5 million years. Developmentally important genes made
      a significant contribution to phylogenetic structure, and rates of genetic
      evolution were high in bmp4, similar to other coding nuclear genes, but low in
      otx1 and the dlx2 exons. Synonymous and non-synonymous substitution patterns in
      developmental regulatory genes support the hypothesis of stabilizing selection
      during the history of these genes, with several phylogenetic regions of
      accelerated non-synonymous change detected in the phylogeny.

PMID- 18621135
TI  - The function of Stat3 in tumor cells and their microenvironment.
AB  - Stat3 was initially recognized as a transcription factor and mediates the nuclear
      action of many different cytokines and growth factors. In addition to its roles
      in normal cell function, the inappropriate activation of Stat3 in tumor cells has
      attracted the attention of tumor biologists and has led to the consideration of
      Stat3 as a drug target. The induction of Stat3 activity under physiological
      circumstances is transient and many different levels of activation and
      deactivation have been defined. In addition to kinases and phosphatases, the SOCS
      proteins and the PIAS proteins have been recognized as negatively regulating
      components, which fine-tune the extent and the duration of Stat3 function. Its
      nuclear cytoplasmic shuttling is exquisitely regulated and adds to the complexity
      of Stat3 action. Newly discovered associations with cytoplasmic molecules suggest
      functions outside the conventional transcriptional regulation context. High
      molecular weight transcription complexes suggest that Stat3 might assume roles in
      transcriptional induction as well as in transcriptional suppression. The aberrant
      activation in tumor cells and the central function of Stat3 in the communication
      between cells of the immune system and tumor cells are of great interest for
      translational research projects and innovative drug development.

PMID- 18621136
TI  - Use of respiratory medication in five Latin American cities: The PLATINO study.
AB  - BACKGROUND: There is scanty information regarding respiratory medication
      prescription pattern in Latin America. We examined the use of bronchodilators and
      corticosteroids in a population-based study conducted in five Latin American
      cities. METHODS: Medication use was derived from questions regarding the use of
      medication "to help breathing" within the previous 12 months, type of medicine,
      and frequency of use. To minimize the possibility of overdiagnosis, we used
      postbronchodilator FEV(1)/FVC<0.70 plus FEV(1)<80% as the definition of
      obstruction. RESULTS: Interviews were completed in 5571 subjects from 6711
      eligible individuals, and spirometry was performed in 5314 subjects. There were
      360 (6.5%) treated subjects and 5211 not treated. Treated subjects were more
      likely to be older, women, unemployed, have higher tobacco consumption, higher
      body mass index, higher FEV(1) reversibility and airway obstruction. They were
      also more likely to report prior spirometry, prior diagnosis of COPD, asthma or
      tuberculosis, and more respiratory symptoms. Over half of treated subjects had
      neither obstruction nor FEV(1) reversibility, and approximately 30% reported no
      prior diagnosis of asthma or COPD. Prior respiratory diagnoses and wheezing were
      more strongly associated with treatment than objective measures of airway
      obstruction. CONCLUSIONS: The use of bronchodilators and/or corticosteroids is
      common in the general population aged 40 years or older, with over one-half of
      treated subjects using them without being obstructed.

PMID- 18621137
TI  - Inhaled ethanol potentiates the cough response to capsaicin in patients with
      airway sensory hyperreactivity.
AB  - A suggested explanation for airway symptoms induced by chemicals and scents is
      sensory hyperreactivity (SHR) of airway mucosal nerves. Patients with SHR have
      increased cough sensitivity to inhaled capsaicin, mediated by transient receptor
      potential (TRP) ion channels. In animal experiments, some TRP receptors are
      potentiated by ethanol, which is why in this study, the aim was to evaluate
      whether a pre-inhalation of ethanol could influence the capsaicin cough response
      in patients with SHR. Fifteen patients with SHR and 15 healthy controls were
      provoked on three occasions with two concentrations of inhaled capsaicin. Before
      each capsaicin provocation, a pre-inhalation of saline or one of two
      concentrations of ethanol was given in a double-blind, randomized fashion. The
      participants reacted in a dose-dependent way with cough on the capsaicin
      inhalations. Among the patients, but not in the control group, pre-inhalation of
      ethanol increased the cough response dose-dependently. The results suggest that
      the pathophysiology of SHR is related to airway mucosal TRP receptors in the
      sensory nerves. In scented products, the combination of ethanol as a solvent and
      perfume may augment an airway reaction in sensitive individuals.

PMID- 18621138
TI  - Effect of hyperosmotic stimulation on aquaporins gene expression in chick kidney.
AB  - Birds can produce hyperosmotic urine, but their renal morphology differs from
      that of mammals. Recent studies in mammals, suggested that various aquaporins
      (AQPs) are present in the kidney and play crucial roles in urine production. To
      elucidate the role of AQPs in the avian kidney, we first examined for the
      presence of AQP1, 2, 3, 4, 7 and 9 mRNAs in the chick (Gallus gallus) kidney by
      RT-PCR analysis. Next, we quantified variations of AQPs mRNAs levels in chick
      kidney after hyperosmotic stimulation (water-deprivation or salt-loading) by real
      time RT-PCR analysis. Our study showed that in addition to AQP1, 2, 3, 4 and 7,
      chick kidney also expressed AQP9 and that hyperosmotic stimulation induced
      changes in AQPs expression. In particular, water-deprivation increased AQP2 and
      AQP3 mRNAs levels, whereas salt-loading induced a significant increase in AQP1,
      AQP2 and AQP9 mRNAs levels. AQP4 and AQP7 mRNA levels were not affected by any
      hyperosmotic stimulation. Taken together, these results indicated that the
      presence of AQPs in chick kidney is similar to that in mammals, that the chick
      kidney has an additional AQP9 and that AQP1, 2, 3 and 9 may play a crucial but
      different role in water permeability in this organ.

PMID- 18621139
TI  - Differential gene expression of fatty acid binding proteins during porcine
      adipogenesis.
AB  - Four different subtypes of fatty acid binding proteins i.e. liver-type FABP1,
      heart/muscle-type FABP3, adipocyte-type FABP4 and epithelial/epidermal-type FABP5
      are expressed in adipose tissue. However, only the regulatory role of FABP4 in
      adipogenesis has been thoroughly investigated. To increase the knowledge on
      possible roles of these FABP subtypes in preadipocyte differentiation, gene
      expression patterns were examined during adipogenesis in pig (Sus scrofa). FABP1
      expression was induced in proliferating cells, whereas FABP3, FABP4 and FABP5
      expression increased throughout preadipocyte differentiation. Interestingly, the
      FABP4 and FABP5 expression increased early in the differentiation, followed by
      FABP3 later in the differentiation process. This indicates a role of FABP4 and
      FABP5 in intracellular fatty acid transport during initiation of differentiation,
      whereas, FABP3 likely is involved in the transport of fatty acids during
      intermediate stages of adipogenesis. In this study we demonstrate that FABP3,
      FABP4 and FABP5 expression is correlated with that of the peroxisome proliferator
      activated receptors alpha and gamma (PPARA and PPARG). Altogether, this suggests
      a role of FABP1 during cell proliferation, whereas a coordinated expression of
      FABP3, FABP4 and FABP5 together with that of PPARA, PPARG1 and PPARG2 might be
      critical for the metabolic regulation during porcine adipogenesis.

PMID- 18621142
TI  - Interactions between trypanosomes and tsetse flies.
AB  - African trypanosomes are insect-borne parasites that cause sleeping sickness in
      humans and nagana in domesticated animals. Successful transmission is the outcome
      of crosstalk between the trypanosome and its insect vector, the tsetse fly. This
      enables the parasite to undergo successive rounds of differentiation,
      proliferation and migration, culminating in the infection of a new mammalian
      host. Several stage- and species-specific parasite surface molecules have been
      identified and there are new insights into their regulation in the fly. Tsetse
      flies are often refractory to infection with trypanosomes. While many
      environmental and physiological factors are known to influence infection, our
      detailed understanding of tsetse-trypanosome relationships is still in its
      infancy. Recent studies have identified a number of tsetse genes that show
      altered expression patterns in response to microbial infections, some of which
      have also been implicated in modulating trypanosome transmission.

PMID- 18621143
TI  - The micronucleus test and erythropoiesis: effects of cyclic adenosine
      monophosphate (cAMP) on micronucleus formation.
AB  - The aim of this study was to determine the mechanism of the rodent bone marrow
      micronucleus test in relation to erythropoiesis. We have previously reported that
      an acceleration of erythropoiesis increases the frequency of micronucleated
      polychromatic erythrocytes (MPCE) induced by mutagens. The blood plasma
      erythropoietin level increased after the injection of N6-2-O-dibutyladenosine
      3',5'-cyclic monophosphate into adenosine 3',5'-cyclic monophosphate (cAMP) at a
      dose of 500 mg/kg. A peak of erythropoietin induction was observed 3 h after the
      injection of cAMP. cAMP itself did not induce any micronuclei in erythroblasts of
      BALB/c mice. So, the frequency of MPCE did not increase after injection of cAMP.
      The highest frequency of MPCE and the dose-response relationship between the cAMP
      doses and micronucleus frequency were observed 30 h after injection of mitomycin
      C (MMC) in mice which had been administered cAMP 24 h previously. The highest
      effect of cAMP on the increase of MPCE was observed when cAMP was given 24 h
      before MMC injection, thus indicating that accelerating the multiplication of
      erythroblasts increases the frequency of MPCE induced by mutagens. The induction
      of MPCE in the bone marrow by three other chemicals (carboquone, 5-fluorouracil,
      and vincristine) also increased after pretreatment with cAMP. Our results suggest
      that the increase of MPCE induced by mutagens can be amplified following the
      acceleration of erythropoiesis by pretreatment with cAMP.

PMID- 18621144
TI  - Two pathways for lysophosphatidic acid production.
AB  - Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) is a simple
      phospholipid but displays an intriguing cell biology that is mediated via
      interactions with G protein-coupled seven transmembrane receptors (GPCRs). So
      far, five GPCRs, designated LPA1-5, and, more recently, two additional GPCRs,
      GPR87 and P2Y5, have been identified as receptors for LPA. These LPA receptors
      can be classified into two families, the EDG and P2Y families, depending on their
      primary structures. Recent studies on gene targeting mice and family diseases of
      these receptors revealed that LPA is involved in both pathological and
      physiological states including brain development (LPA1), neuropathy pain (LPA1),
      lung fibrosis (LPA1), renal fibrosis (LPA1) protection against radiation-induced
      intestinal injury (LPA2), implantation (LPA3) and hair growth (P2Y5). LPA is
      produced both in cells and biological fluids, where multiple synthetic reactions
      occur. There are at least two pathways for LPA production. In serum or plasma,
      LPA is predominantly produced by a plasma enzyme called autotaxin (ATX). ATX is a
      multifunctional ectoenzyme and is involved in many patho-physiological conditions
      such as cancer, neuropathy pain, lymphocyte tracking in lymph nodes, obesity,
      diabetes and embryonic blood vessel formation. LPA is also produced from
      phosphatidic acid (PA) by its deacylation catalyzed by phospholipase A (PLA)-type
      enzymes. However, the physiological roles of this pathway as well as the enzymes
      involved remained to be solved. A number of phospholipase A1 and A2 isozymes
      could be involved in this pathway. One PA-selective PLA1 called mPA
      PLA1alpha/LIPH is specifically expressed in hair follicles, where it has a
      critical role in hair growth by producing LPA through a novel LPA receptor called
      P2Y5.

PMID- 18621145
TI  - Caste- and sex-specific adaptations within the olfactory pathway in the brain of
      the ant Camponotus floridanus.
AB  - Olfaction plays a key role in mediating ant behavior, and ant societies are
      characterized by caste- and sex-specific division of labor. We propose that caste
      and sex-specific adaptations in the olfactory pathway promote differences in
      olfactory behavior. This study compares olfactory centers in the brain of large
      (major) workers, small (minor) workers, virgin queens, and males of the carpenter
      ant Camponotus floridanus. The number of glomeruli in the antennal lobe was
      similar in the female castes, although the glomerular volumes differed. Males had
      approximately 45% fewer glomeruli compared to females (approximately 258 and
      approximately 434) and one antennal sensory tract was absent. A dual output
      pathway to the mushroom bodies was present in males. In contrast to females,
      however, the number of glomeruli connected to the medial antennocerebral tract
      was substantially smaller than those associated with the lateral tract. All
      glomeruli in the male antennal lobe contained serotonergic processes, whereas in
      the female castes glomeruli in the large tract six cluster lacked serotonergic
      innervations. We conclude that differences in general glomerular organization are
      subtle among the female castes, but sex-specific differences in the number,
      connectivity and neuromodulatory innervation of glomeruli are substantial and
      likely to underlie differences in olfactory processing and learning.

PMID- 18621146
TI  - How many modes of action should an antibiotic have?
AB  - All antibiotics that have been successfully employed for decades as
      monotherapeutics in the treatment of bacterial infections rely on mechanisms of
      bacterial growth inhibition which are by far more complex than inhibition of a
      single enzyme. Such successful antibiotics have in common that they address
      several targets in parallel and/or that their targets are encoded by multiple
      genes. Such multiplicity of targets and of target genes has the advantage that
      the emergence of spontaneous target-related resistance is a comparatively slow
      process. Recently registered antibiotics and novel antibiotics in development are
      discussed in the light of this promising concept of antibacterial
      polypharmacology.

PMID- 18621147
TI  - Group therapy for patients with psychogenic nonepileptic seizures: a pilot study.
AB  - Great advances have been made in the diagnosis of people with psychogenic
      nonepileptic seizures (PNES) since the advent of video/EEG monitoring. However,
      treatment options for this population have lagged significantly. This pilot study
      was undertaken to evaluate whether group therapy done with a psychodynamic focus
      would offer a useful intervention. Twelve patients entered the study and seven
      completed at least 75% of the 32 weekly sessions. The Beck Depression Inventory
      and the Global Severity Index of the Symptom Checklist-90 showed improvement as
      well as an overall decrease in PNES frequency. The data suggest that group
      therapy focusing on interpersonal issues may benefit patients with PNES.

PMID- 18621148
TI  - Disruption of circulation by ethanol promotes fetal alcohol spectrum disorder
      (FASD) in medaka (Oryzias latipes) embryogenesis.
AB  - Japanese medaka (Oryzias latipes) embryos exposed to ethanol have developed
      craniofacial, cardiovascular and skeletal defects which can be compared with the
      phenotypic features of fetal alcohol spectrum disorder (FASD) observed in human.
      The present experiment was designed to show that the disruption in circulation by
      ethanol during embryogenesis is a potential cause of FASD. Fertilized eggs were
      exposed to ethanol (0, 100 and/or 400 mM) for 24 or 48 h at various developmental
      stages (Iwamatsu stages 4-30) and were analyzed at 6 day post fertilization
      (dpf). It was observed that controls and the embryos exposed to 100 mM ethanol
      were in circulating state; however, a significant number of embryos of stages 4
      24 exposed to 400 mM ethanol had disrupted circulation. Compared to controls,
      protein and RNA contents were significantly reduced in non-circulating embryos.
      Lipid peroxidation (LPO) analysis was made at 3, 6, 24, 48, 96 and 144 hour post
      fertilization (hpf). LPO was increased with the advancement of morphogenesis;
      however, ethanol or the circulation status had no effect. We further analyzed
      alcohol dehydrogenase (Adh 5 and adh8) and aldehyde dehydrogenase (Aldh9A and
      Aldh1A2) enzyme mRNAs in the embryos exposed to 400 mM ethanol for 24 h. A
      developmental stage-specific reduction in these enzyme mRNAs by ethanol was
      observed. We conclude that ethanol-induced disruption in circulation during
      embryogenesis is a potential cause of the development of FASD features in medaka.

PMID- 18621149
TI  - The effects of a primary-treated municipal effluent on the immune system of
      rainbow trout (Oncorhynchus mykiss): exposure duration and contribution of
      suspended particles.
AB  - Municipal sewage effluents are complex mixtures of contaminants known to disrupt
      both immune and endocrine functions in aquatic organisms. The present study
      sought to determine the impacts of municipal effluent on the immune systems of
      juvenile rainbow trout (Oncorhynchus mykiss), by exposing specimens to low
      concentrations (0.01%, 0.1%, 1% or 10%) of sewage effluent for periods of 28 or
      90 days. The soluble and insoluble fractions of the effluent were also studied to
      assess the contribution of fractions rich in microorganisms and particles on fish
      immune systems. To this end, the trout were also exposed to soluble and insoluble
      fractions of the effluent for a period of 28 days. Immunocompetence was assessed
      by the following three parameters: phagocytosis, natural cytotoxic cells (NCC)
      and blastogenesis of lymphocytes under mitogen stimulation. Fish exposed to the
      1% sewage effluent concentration for 28 days had enhanced phagocytic activity; at
      90 days, phagocytic activity was reduced. T and B lymphocyte proliferation in
      fish from both groups was similarly stimulated. Phagocytosis and NCC activities
      were influenced more by the insoluble fraction than the soluble fraction of the
      effluent. Conversely, mitogen-stimulated T lymphocyte proliferation was enhanced
      in cells of fish exposed to the soluble fraction of the effluents, with a
      dampening effect on the insoluble (particulate) fraction of the effluent. In
      conclusion, the effects of the effluent and its fractions were higher at the
      cellular-mediated immunity level than at the acquired immunity level.
      Immunotoxicity data on the soluble fraction of the effluent were more closely
      associated to data on the unfractionated effluent, but the contribution of the
      particulate fraction could not be completely ignored for phagocytosis and B
      lymphocyte proliferation.

PMID- 18621150
TI  - Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis in LPS
      stimulated RAW264.7 macrophages.
AB  - The anti-inflammatory effects of glycyrol, a benzofuran coumarin isolated from
      Glycyrrhizae Radix, were studied. Glycyrol of 5, 25 and 50 microM dose
      dependently inhibited nitric oxide (NO) production by down-regulating inducible
      nitric oxide synthase (iNOS), and alleviated cyclooxygenase-2 (COX-2) expression
      in LPS-stimulated RAW264.7 macrophages, in both the mRNA and the protein.
      Furthermore, glycyrol dose-dependently decreased the mRNA of the pro-inflammatory
      cytokines IL-1beta and IL-6. LPS-induced NF-kappaB activation was prevented in
      RAW264.7 macrophages by inhibition of I-kappaBalpha phosphorylation. In addition,
      administration of glycyrol (30 and 100 mg/kg, i.p) reduced the thickness of
      carrageenan-induced mouse-paw edema swelling. Taken together, our results
      indicate that glycyrol is an important anti-inflammatory constituent of
      Glycyrrhizae Radix, and that its anti-inflammatory effect is attributed to the
      inhibition I-kappaBalpha phosphorylation.

PMID- 18621151
TI  - Characterization of the transduction pathway involved in c-fos and c-jun
      expression induced by Aggregatibacter actinomycetemcomitans lipopolysaccharides
      in human gingival fibroblasts.
AB  - Periodontal disease is an inflammatory disease caused by infection with oral
      bacteria that results in tooth exfoliation. Lipopolysaccharides (LPS) are a major
      component of the outer membrane of Gram-negative microorganisms and are involved
      in the inflammatory response. c-fos and c-jun are involved in pathological
      conditions such as inflammatory disorders. Inflammatory signaling cascades
      leading to c-fos activation in human gingival fibroblasts (HGFs) are not well
      characterized. Thus, we have investigated the kinase pathways involved in c-fos
      and c-jun activation induced by LPS in human gingival fibroblasts. LPS promoted a
      dose- and time-dependent increase in c-fos transcription. Phosphoinositide
      phospholipase C inhibitor (U-73122), protein kinase A inhibitor (H89), MEK1
      inhibitor (PD 98,059), p38 inhibitor (SB203580), and tyrosine kinase inhibitors
      (genistein and herbimycin) attenuated the LPS effect, while the PI-3 K inhibitor
      (Wortmannin) had no effect on LPS-induced c-fos transcription. Protein kinase C
      inhibitors (Ro 31-8220, calphostin C, staurosporine, and chelerythrine chloride)
      also inhibited LPS-induced c-fos transcription. However, long-term treatment (24 
      h) with the PKC activator tetradecanoyl phorbol-13-acetate (PMA) had no
      significant effect on LPS-induced transcription in HGFs. We also found an
      increase in c-jun expression in HGF stimulated with LPS. In addition, experiments
      using pharmacological inhibitors of individual mitogen-activated protein kinases
      (MAPK) and of protein kinase C (PKC) revealed that p38, ERK 1/2, and PKC are
      involved in LPS-induced c-jun expression. Our results indicate that LPS-induced c
      fos and c-jun expressions are mediated by two different signaling pathways: one
      through phosphoinositide-phospholipase C via an upstream protein tyrosine kinase,
      which activates PKC isoforms that are insensitive to phorbol stress, and the
      second through activation of protein kinase A (PKA). Both kinases regulate the
      phosphorylation of the extracellular signal-regulated kinase ERK 1/2 and p38.

PMID- 18621152
TI  - Nephrocytes of harvestmen, Leiobunum limbatum and L. rotundum.
AB  - Nephrocytes are said to be able to take up substances from the hemolymph. In
      Opiliones, which were examined electron microscopically three different types of
      nephrocytes were found. Numerous large nephrocytes lie clustered between the
      muscles in the anterior region of the body. Smaller nephrocytes occur scattered
      throughout the opilionid body, often affixed to tracheoles. The third group,
      pericardial cells, are always attached to the heart wall by connective ligaments.
      All nephrocytes are surrounded by a thick basement membrane and their plasma
      membrane forms pedicels. Junctional complexes link the adjacent pedicels to form
      diaphragm-like slit-membranes, which form the entrance to an extracellular
      compartment. The cytoplasm of the nephrocytes contains many pinocytotic vesicles
      and tubular elements. Different types of large electron-dense and electron-lucent
      vesicles can be distinguished. Occasionally a large bundle of unmyelinated nerve
      fibers is enclosed by a pericardial cell. Morphological differences between the
      types of nephrocytes are described and the ultrastructural characteristics of the
      nephrocytes of harvestmen are compared with those of other arthropods. Functional
      aspects are discussed with respect to their ultrafiltration structures.

PMID- 18621153
TI  - Fine structure and histochemistry of the ampullary organ of the urodele amphibian
      Pleurodeles.
AB  - A morphological study by light and electron microscopy on the lateral line system
      of the urodele amphibian Pleurodeles waltii demonstrates the presence of sensory
      organs other than neuromasts in the head. From their morphology, they have been
      called ampullary organs. The ampullary organs occur in the bottom of a groove and
      consist of three different types of cells: sensory, supporting and mantle cells.
      Histochemical analysis indicates that the last two are secretory cells, probably
      involved in the production of the material filling the ampulla and the groove.

PMID- 18621154
TI  - Extracellular matrix of the regeneration chamber and plasma membranes of the
      epidermis during leg regeneration in an insect Carausius morosus.
AB  - An extracellular matrix (ECM) is found in the regeneration chamber during leg
      regeneration in the stick insect Carausius morosus. The material which surrounds
      the regenerate is organised into fibrils and it includes proteins distributed in
      a hydrated polysaccharide gel. The compounds which can be demonstrated are chitin
      unlinked to proteins, glycoproteins and unsulfated glycosaminoglycans such as
      hyaluronic acid and/or chondroitin. Molecules related to vertebrate fibronectin
      and collagen IV were observed on the apical surface of the epidermal cells of the
      regenerate. During leg regeneration, the basal lamina which normally secures the
      cells to each other is absent. However a condensation of material on the
      regenerate epidermal cells ensures their cohesion. The extracellular matrix in
      the regeneration chamber must be secreted by the cells of retracted epidermis and
      then by the epidermal cells of the regenerate, until these cells are able to
      secrete the cuticle for the next instar. The analysis of the epidermal cell
      surface does not seem to show any localization or any changes during the
      development of the regenerate.

PMID- 18621155
TI  - The distribution of aeriferous tracheae for the ovaries of insects.
AB  - Examination of the tracheal supply to the ovaries in insects selected from nine
      orders shows that the main tracheae are always of the aeriferous type:
      characterized by a coating of spiral tubules with permeable cuticle which bring
      the tracheal air into close contact with the haemolymph. The structure of these
      tracheae is constant, from large tracheae exceeding 50 mum in diameter to small
      vessels with diameter a small fraction of 1 mum. On the other hand there is great
      diversity in the methods by which oxygen is delivered to the individual oocytes,
      some of which are briefly defined.

PMID- 18621156
TI  - Mesothoracic interneurons involved in flight steering in the locust.

PMID- 18621157
TI  - Fine structure of the spermatozoon of the strepsipteran Xenos moutoni.
AB  - Spermatozoa of Xenos moutoni De Buysson belonging to the order Strepsiptera
      (Insecta) were examined by electron microscopy. The spermatozoon was seen to have
      an elongated head and a tail containing a 9+9+2 axoneme and two mitochondrial
      derivatives of equal size. The pear-shaped acrosome is characterised by a mono
      layered structure and terminates anteriorly forming two pyramidal evaginations.
      The nucleus exhibits an external portion of dense chromatin and an internal one
      of uncondensed material. The latter occupies a central position at the base and
      becomes progressively peripheral at the apex. The tail is long and in its final
      portion the axoneme loses its elements progressively. These results have been
      compared with the ultrastructure of the spermatozoa of Coleoptera which have been
      considered as a sister group of Strepsiptera.

PMID- 18621158
TI  - Methylene blue filling of the dorsal giant fibres of the earthworm by
      electrophoresis.
AB  - Multisegmental methylene blue filling of the three dorsal giant fibres in the
      nervous system of the earthworm was obtained by the use of electrophoresis. There
      was no difference in aldehyde fixed and unfixed tissue; due to its larger
      diameter, the median giant fibre could be stained over longer distances than the
      lateral ones. Accumulations of the dye were detected in the median giant fibre in
      the dorsal openings of the myelin sheath and at the origins of the ventral
      branches descending from both fibre systems. Since no significant axonal filling
      was observed by using several other dyes similar to methylene blue in diffusion
      and dialysis properties, the staining mechanism obviously depends on the specific
      binding sites of methylene blue in combination with the current. Therefore, the
      revealed phenomena provides evidence of a direct correlation between methyelne
      blue coupling and electrical coupling in the dorsal giant fibres of the
      earthworm.

PMID- 18621159
TI  - Membrane specializations in flagellar ribbons of elasmobranch fish.
AB  - Specialized epithelial cells lining the elasmobranch nephron bear numerous
      flagella which are organized into closely-packed, parallel rows forming ribbons
      (Lacy et al., 1989a). The compact arrangement of the adjacent flagella comprising
      each ribbon suggests they are structurally bound together, forming a single unit
      which functions to force urine along the nephric tubule. In the present study,
      the structural basis of the interflagellar connections was investigated by
      scanning electron microscopy (SEM) and by transmission electron microscopy (TEM)
      of thin sections and freeze fracture replicas. Various fixatives and
      histochemical stains were used to elucidate the structure and composition of the
      interflagellar adhesive material. SEM of the luminal cell surface showed the
      organization of the flagella in ribbons. In TEM, fixation in a solution
      containing glutaraldehyde and tannic acid, Ruthenium red or Alcian blue, or
      postfixation in reduced OsO(4) revealed that the plasma membrane of each
      flagellum of a ribbon was surrounded by a thin layer of surface coat composed of
      very short filaments more prominent at sites where adjacent flagella were in
      close apposition. In comparable locations, freeze-fracture replicas disclosed
      small aggregates or plaques of particles arranged in an irregular, discontinuous
      line on both faces P and E of the flagellar membrane. In areas where the flagella
      were not arranged into ribbons (most frequently after immersion fixation), the
      surface coat was thick and expanded and, in replicas, the intramembranous
      particles were randomly scattered. All of these plasma membrane specializations
      appear to function in binding adjacent flagella and thus facilitate a coordinated
      flagellar ribbon beat.

PMID- 18621160
TI  - Absorption of phosphorus from the spermatophore through the cuticle of the bursa
      copulatrix of the butterfly, Calpodes ethlius.
AB  - In lepidoptera the spermatophore is deposited in a bursa copulatrix, which is
      lined by a cuticle through which solubilized components of the spermatophore must
      be absorbed by the underlying epithelium. This study follows the route taken by
      the phosphorus which, with calcium, forms a significant portion of the
      spermatophore of Calpodes ethlius in the form of homogeneous, amorphous
      concretions. Lead nitrate was used in the primary fixative to precipitate the
      phosphorus in order to follow the pathway taken by it through the cuticle and
      bursal epithelium. The epicuticle-free pits, which cover the bursal cuticle, are
      identified as the points of entry, and the epicuticular filaments as major
      pathways for transport of phosphorus and presumably soluble molecules. Lead
      phosphate deposits also occurred in the epithelium extracellularly between the
      apical microvilli, lateral membranes and basal folds, in calcium granules and in
      large compound structures which appear to be made up, at least in part, of
      calcium granules. The confinement of the phosphorus to extracellular compartments
      of the epithelium suggests that its function is to be found elsewhere.

PMID- 18621161
TI  - Distribution of serotonin-, Gamma-Aminobutyric Acid- and substance P-like
      immunoreactivity in the central and peripheral nervous system of Mytilus
      galloprovincialis.
AB  - The distribution of serotonin-, GABA- and substance P-like immunoreactivity has
      been studied in the cerebral and visceral ganglia and in some peripheral tissues
      of Mytilus galloprovincialis (Moleusca, Bivalvia). Cerebral ganglia contain a
      developed serotonin-immunoreactive neuronal subpopulation and numerous GABA
      immunoreactive neurons, whereas neurons positive for substance P are sparse. In
      peripheral tissues innervated by the cerebral ganglia (labial palps and
      oesophagus) only serotonin-immunoreactive nerve fibers were found. In the
      visceral ganglia, serotonin- and GABA-immunoreactive neurons are far less
      numerous than in the cerebral ganglia, whereas several neurons positive for
      substance P are scattered in all cortical zones. Serotonin-immunoreactive
      plexuses innervate the posterior adductor muscle and the gill filaments which
      contain also a developed nerve network positive for substance P. The distribution
      pattern of the immunoreactive elements in the ganglia and in peripheral
      territories indicates that GABA should exert only a central action, whereas
      serotonin and a substance P-like peptide are involved both in central and
      peripheral neurotransmission.

PMID- 18621162
TI  - The organization of exteroceptive sensory inputs to interneurons of the flight
      neuropil in locusts.
AB  - 1. Thirty-seven pairs of mesothoracic interneurons respond selectively to visual
      or ocellar stimuli corresponding to deviations from course in flight, expressed
      as angular rotation around the three spatial axes. 2. Sensitivities to roll and
      yaw are very strongly associated. All interneurons showing a directional
      preference for yaw rotations showed the same preference for roll rotations. A few
      roll-sensitive cells were not directionally sensitive to yaw. Some interneurons
      respond exclusively to pitch rotations, most to both pitch and roll/yaw. 3.
      Approximately equal numbers of interneurons prefer pitch up, pitch down, roll/yaw
      to the ipsilateral side and roll/yaw to the contralateral side. All four possible
      combinations of pitch (up or down) with roll/yaw (ipsilateral or contralateral)
      preferences occur with equal probability. 4. No relationship between neuronal
      structure and directional properties could be discerned. 5. The average latency
      of the ocellar EPSPs recorded in the interneurons is not significantly different
      from the average latency of the ocellar spike in the descending neurons (at the
      same temperature and in the same ganglion). The average ocellar IPSP latency is
      8.5 ms longer. The data support the hypothesis that most EPSPs are derived from
      monosynaptic inputs from the DNs, and most IPSPs from polysynaptic inputs. A few
      EPSPs are also derived from polysynaptic inputs. 6. Most of these neurons are
      sensitive to wind, at least some directionally so, in a manner functionally
      compatible with their visual or ocellar directionality, and most are excited. Two
      neurons respond to movement of small objects in the visual field, and 5 to high
      frequency sound.

PMID- 18621163
TI  - Tissue distribution and levels of natural and induced serum lysozyme
      immunoreactive molecules in a freshwater snail.
AB  - Lysozyme immunoreactive molecules (irLm) in Planorbarius corneus was demonstrated
      by an immunocytochemical method in oocytes, the kidney, spreading phagocytic
      hemocytes (SH), digestive phagocytic cells, and epithelial cells of the stomach
      and intestine. Three hr after the injection of a variety of bacteria or
      substances (S. aureus, E. coli, E. coli LPS, latex particles, PBS) a
      statistically significant increase in irLm serum level was detected by the
      microELISA method. Twenty-four hr later, this increase was detected only in
      specimens which had been injected with bacteria. A similar response was observed
      14 days later, following a second injection of the above-mentioned substances in
      the same snails. The results suggest that: 1) irLm appears to be an inducible
      molecule responding non-specifically to foreign challenge; 2) no anamnestic
      response is observed for irLm; 3) a relationship exists between irLm and
      phagocytosis; indeed, irLm have chemotactic activity towards SH; 4) serum irLm
      probably originates from different sources; in fact, they are released from SH
      and the kidney. The increase in the serum irLm level is responsible, at least in
      part, for the lytic attack and death of bacteria, but it is probably also
      involved in unspecific inflammatory reactions.

PMID- 18621164
TI  - Endothelial nuclear bulging: Morphological evidence for an intraglomerular
      perfusion regulating mechanism in the axolotl.
AB  - Kidneys of the Axolotl (Ambystoma mexicanum: Urodela, Amphibia) have been
      investigated by light and electron microscopy as well as microvascular corrosion
      casting. Numerous glomerular endothelial nuclei bulge into the glomerular
      capillary lumen. It is concluded that these cells virtually stop the blood-flow
      in the respective vessel by blockage of erythrocyte passage. A proposal for an
      intraglomerular regulation mechanism of capillary perfusion (and thus filtration)
      by endothelial isometric contraction in the Axolotl is made on the basis of
      morphological methods.

PMID- 18621165
TI  - A quantitative ultrastructural study of the honeybee antennal lobe.
AB  - This paper describes the ultrastructural organization of the honeybee antennal
      lobe, including the distribution of synapses within the antennal lobe neuropile
      and the distribution of the afferent fibres in the antennal nerve and its
      afferent tracts. We show that: 1) The antennal nerve and tracts T3-T6 are
      composed of a heterogeneous population of fibres, with respect to their
      diameters, whereas two afferent tracts (T1 and T2) are composed of fibres of
      almost homogeneous diameter. 2) Synapses are mainly localized in the glomeruli
      with a higher frequency in the cortical layer than in the core of the glomerulus.
      Nevertheless a few synapses are found in the coarse neuropile. 3) Reciprocal
      synapses have been identified in the cortical layer. At the ultrastructural
      level, the organization of the bee antennal lobe was largely unknown and these
      results bring the anatomical background needed in order to carry out a
      developmental study related to the bee antennal lobe structures.

PMID- 18621166
TI  - Ultrastructural analysis of the morphology and function of the spermatheca of the
      pulmonate slug Arion subfuscus.
AB  - A study of the histology, histochemistry and ultrastructure of the spermatheca of
      Arion subfuscus in different stages of its life cycle shows that the spermatheca,
      an accessory organ of the femal genital tract of pulmonates, is a spherical
      shaped organ lined with a columnar and non-ciliated epithelium surrounded by a
      thin network of connective tissue with some muscle fibres. The narrow epithelial
      cells possess numerous microvilli that, excepting young specimens, are provided
      with long, thin and generally curved, membranous process. Golgi apparatus, RER
      and mitochondria are abundant. Basal infolds are not very deep. In specimens
      killed two days after-copula, the spermatheca is swollen and its lumen is full of
      degenerating spermatozoa, mucus masses and spermatophore fragments. The apex of
      the cell is rich in granules with varied content, including multivesicular
      bodies. In specimens killed two weeks after-copula there are numerous endocytic
      vesicles in the apex and big vacuoles containing lipid. It is considered that
      after mating the excess of exogenous spermatozoa and copulatory seminal fluids
      are digested in the spermatheca. First, there is extracellular digestion that may
      be carried out by the enzymes contained in the multivesicular bodies exocytosed
      to the lumen, as well as by the enzymes secreted in apocrine vesicles. The
      partially digested materials would then be absorbed by endocytosis and further
      digested intracellularly. The great accumulation of lipid in the epithelial cells
      two weeks after mating suggest that the spermatheca could be involved in lipid
      synthesis, acting as a reserve organ.

PMID- 18621167
TI  - Apoferritin in the vacuolar system of insect hemocytes.
AB  - Electron microscopy showed no holoferritin in either the cytosol or the vacuolar
      system of hemocytes (granulocytes) from normal Calpodes ethlius larvae. This does
      not mean that ferritin is normally absent from hemocytes, since apoferritin lacks
      contrast and would not be observed. In vitro iron in glycerol treatment of
      hemocytes from normal larvae caused holoferritin cores to be visible in the rough
      endoplasmic reticulum, suggesting that hemocytes from normal larvae contain
      apoferritin. Hemocytes are therefore like the fat body, and could also be a
      source of hemolymph ferritin. After loading the hemolymph with iron in vivo, many
      holoferritin cores were resolvable in the vacuolar system of some hemocytes.
      Ferritin synthesis can therefore be induced by elevated hemolymph iron levels.
      Iron loading of epidermis and heart showed similar ferritin cores but more
      rarely. In all tissues they occurred in the secretory pathway and not in the
      cytosol.

PMID- 18621168
TI  - Distribution of sulfhydryloxidase (SOx) immunoreactivity in the testis of the
      axolotl (Ambystoma mexicanum) (amphibia, urodela).
AB  - Immunohistochemical localization of sulfhydryloxidase (SOx) has been examined in
      the testis of the Axolotl (Ambystoma mexicanum). The urodelan testis contains
      germ cells in various phases of differentiation from primordial germ cells to
      mature spermatozoa. SOx immunoreactivity is present in mitochondria of primordial
      germ cells and primary spermatogonia and declines within the population of
      secondary spermatogonia, suggesting, that the antibody used to localize SOx may
      serve to estimate the developmental stage of spermatogonia towards meiosis, since
      more undifferentiated cells react positively. Intensity of immunostaining
      increases again in spermatocytes and becomes most intense in early round
      spermatids correlating on ultrastructural level with an accumulation of numerous
      mitochondria in that part of the cytoplasm, where the acrosome vesicle is formed.
      Mature sperm are immunonegative. Additionally, Leydig cells within the glandular
      tissue are stained by the antibody. Thus the distribution pattern of SOx
      immunoreactivity principally resembles that in the mammalian testis found during
      ontogenesis or in the adult seminiferous epithelium. The possible functional
      significance of mitochondrial SOx in germ cells and Leydig cells is discussed.
      These results suggest, that the amphibian testis is a model for experimental
      problems dealing with the investigation of germ cells in various developmental
      phases including very undifferentiated premeiotic germ cells. The cystic testis
      may be of value in studying influences of various experimental conditions on
      varied homogeneous populations of germ cells.

PMID- 18621169
TI  - Ultrastructure of the pronephric kidney of embryos and prolarvae of the sea
      lamprey, Petromyzon marinus.
AB  - Embryos of lampreys Petromyzon marinus were obtained through a technique of
      artificial fertilization. Samples of developmental intervals to the prolarval
      stage were prepared for transmission electron microscopy and the pronephros was
      examined. The pronephros was visible in the cardiac region of the coelom prior to
      the time of hatching of embryos and consisted of a renal corpuscle, nephrostomes,
      and proximal tubules connected to a pronephric duct. The renal corpuscle was
      comprised of poorly-defined vascular channels and a visceral epithelium of yolk
      filled cells, the podocytes, with short major processes and pedicels resting on a
      basal lamina. The first proximal tubules possessed a delicate brush border of
      short microvilli but subsequent cellular differentiation yielded cells with all
      the components required for the process of endocytosis, a process which was
      demonstrated by uptake of the tracer, horseradish peroxidase. The distal tubules
      appeared later in development and were noted for abundant mitochondria and an
      extensive smooth tubular network. The timing of differentiation of various
      components of the nephron corresponds to that seen during morphogenesis of other
      vertebrate kidneys.

PMID- 18621170
TI  - Growth and differentiation of the larval midgut epithelium during molting in the
      moth, Manduca sexta.
AB  - The number of epithelial cells comprising larval midgut of the tobacco hornworm
      moth, Manduca sexta increases 200-fold in development from the first to the fifth
      instar. We have examined larvae periodically before and during molting to follow
      epithelial cell proliferation and differentiation. The midgut epithelium in
      Manduca sexta consists predominantly of columnar and goblet cells. These are
      arranged in a characteristic pattern with each goblet cell surrounded by a single
      layer of 4-6 columnar cells (Hakim et al., (1988)). While undifferentiated basal
      stem cells are infrequently seen in intermolt larvae, just prior to the period
      when external signs of molting are visible, their number increases and mitotic
      figures become common. Proliferation continues for several hours and then these
      stem cells differentiate following a pattern similar to that seen during
      embryogenesis (Hakim et al., (1988)). Here, however, the newly differentiating
      cells become intercalated among the mature differentiated cells already present
      in the epithelium. Since the pattern of individual goblet cells surrounded by a
      reticulum of columnar cells is maintained after the addition of new cells, the
      midgut epithelium of molting larvae appears to be a useful model for studying
      pattern formation in development.

PMID- 18621171
TI  - Sexual dimorphism of gnathocoxal glands of the spider Leptyphantes
      sanctivincentii.
AB  - The cave-living spider Leptyphantes sanctivincentii (Simon) (Aranea: Liniphiidae)
      is characterized by an extreme sexual dimorphism of its gnathocoxal glands. In
      the female they belong to one type, whereas three different types can be
      identified in the male; the most remarkable is the type III gland, singularized
      by the rice-shaped granules which originate from its complex patterned grains. It
      is likely that the secretion of the male are involved in the course of mating,
      either as a palp 'lubricant', or as a pheromone carrier.

PMID- 18621172
TI  - Evidence for intercellular cohesion in the septate junction of the protozoon
      Gregarina.
AB  - Injection of Lucifer Yellow dye was used to establish whether septate junctions
      formed a permeability barrier between primite and satellite gamonts in the syzygy
      of the protozoon Gregarina. The fluorescent dye did not pass from one cell to the
      other, thus suggesting that the septate junction served only for mechanical
      adhesion. Later on in development, when the gametocyst had formed, the septate
      junction vanished and interruptions were observed between opposing cell
      membranes. At this stage the fluorescent dye was able to pass freely into the
      conjugated cells.

PMID- 18621173
TI  - Cell types differing in thick myofilament diameter in obliquely striated muscle
      of a polychaete annelid, Neanthes.
AB  - The fine structure of the obliquely striated muscle cells of the longitudinal
      muscle of an annelid was investigated. The characteristics of myofilaments and
      cell components, such as sarcoplasmic reticular system (S.R.), T-systems and J
      rods corresponded to those previously reported, but it was noted for the first
      time that the cells could be classified into two types with respect to the
      diameters of their thick myofilaments. In one type, the thick myofilaments were
      about 29 nm in diameter (A-type) and in the other they were about 41 nm in
      diameter (B-type). Most of the obliquely striated muscles described to date have
      been composed of a single type of cell, but we found two types of cell mixed
      together in the longitudinal muscle. The A-type cells with slender thick
      myofilaments were distributed mainly in the inner part of the muscle and the B
      type cells with broader thick myofilaments were distributed in the outer part.

PMID- 18621174
TI  - Seasonal and environmental codes in the chemistry of the scales of the hoki
      Macruronus novaezelandiae.
AB  - Hoki (Macruronus novaezelandiae: Merluccidae) scales do not have conventional
      annual (annuli) marks, but when observed by transmitted light showed light and
      dark bands of the type produced by intra-annual variation in the growth rate of
      the internal lamellae of the scale. The calcium, fluorine, strontium and zinc
      content of the hoki scale was measured with a proton microprobe and showed cycles
      in elemental composition that could be interpreted as seasonal.

PMID- 18621175
TI  - Functional morphology of the divided compound eye of the honeybee drone (Apis
      mellifera).
AB  - Using different approaches, the functional morphology of the compound eye of the
      honeybee drone was examined. The drone exhibits an extended acute zone in the
      dorsal part of its eye. The following specializations were found here: enlarged
      facet diameters; smaller interommatidial angles; red-leaky screening pigment;
      enlarged rhabdom diameters; photopigment composition different from the drone's
      ventral eye region and the worker bee's eye. Thus, similar to other male insects,
      the drone compound eye is divided into a male-specific dorsal part and a ventral
      part resembling the worker bee's eye. The functional significance of the sex
      specific acute zone is discussed with respect to mating behaviour.

PMID- 18621176
TI  - Ultrastructural analysis of sperm flagella in two clitellates (Annelida), plasma
      membrane and periaxonemal area.
AB  - The region between axonemes and plasma membrane in the sperm tails of the
      tubincid oligochaetes Tubifex tubifex and Monopylephorus limosus has been studied
      by means of thin sections of conventionally and tannic acid fixed material, and
      of freeze-fracture replicas. The main portion of the flagellum in both species
      showed prominent, regularly repeating bridges connecting doublets to plasma
      membrane. In correspondence to the doublets, characteristic double rows of
      intramembrane particles are present, with an arrangement reminiscent of the
      "zipper lines" described in other species. A well-developed cortical web with a
      honeycomb appearance underlies the plasma membrane. Glycogen granules are
      regularly arranged within the cells. An outstanding difference between the two
      species is to be found in the presence only in Monopylephorus of complex muff
      like structures apparently formed by membrane particles and series of teeth
      embedded in the cortical web. Nothing similar has been found in Tubifex. This
      difference may be related to the fact that spermatozoa in Monopylephorus are not
      enclosed in spermatozeugmata as are those of Tubifex.

PMID- 18621177
TI  - The morphology and ultrastructure of antennal lobe cells from pupal honeybees
      (Apis mellifera) growing in culture.
AB  - A culture technique for the in vitro growth and differentiation of antennal lobe
      cells from the honeybee, Apis mellifera, is described and the ultrastructure of
      the growing cells is analysed. Two types of cell are present in the cultures and
      from their morphology and ultrastructure they can be identified as glial cells
      and neurones. The neurones have a granular cytoplasm, abundant endoplasmic
      reticulum and a small, densely stained nucleus. They produce long processes with
      varicosities that contain dense-core and clear vesicles. In contrast the glial
      cells have clear cytoplasm, little endoplasmic reticulum and a distinct
      cytoskeletal organisation. These cells produce short, flat processes that spread
      over the surface of the culture dish. Although a number of cell contacts have
      been identified in the cultures no synapses have yet been seen. These cultures
      provide a good in vitro model for an analysis of the interactions between cells
      derived from the antennal lobe of the honey bee.

PMID- 18621178
TI  - Egg envelopes in diplopods, a comparative ultrastructural study.
AB  - By means of electron microscopy two types of egg envelope have been described in
      representatives of two diplopod subclasses, the Chilognatha and the
      Pselaphognatha. The vitelline envelope appears on the oocyte surface in early
      previtellogenesis and persists till ovulation. In its thin and filamentous
      structure it resembles basement membranes. During vitellogenesis electron dense
      material is deposited on filamentous scaffolding which fills the space between
      the oolemma and the vitelline envelope. As a result, the thick and spongy or
      filamentous chorion is formed. In the present study it has been shown that
      regardless of the type of oogenesis (solitary-the Chilognatha, or follicular-the
      Pselaphognatha) both envelopes in diplopods are produced by the oocyte itself,
      and although completely different in structure and time of appearance, they must
      be both considered as primary.

PMID- 18621179
TI  - Structural changes in the proximal tubule of the short-toes axolotl mutant.
AB  - A recessive lethal mutation in axolotls that involves the kidneys, the Mullerian
      ducts and the limbs was described by Humphrey (1967). In the present experiments,
      we have examined the structural defects that lead to kidney malfunction and
      subsequent death in homozygous mutants and compared the defects with those
      observed in other axolotls lacking this mutant gene. The ultrastructure of the
      mesonephric kidney was studied in homozygous s/s short-toes axolotls with ascites
      and/or edema and hemorrhages (group 1a); in s/s short-toes axolotls not yet
      expressing kidney malfunction symptoms (group 1b); in normal siblings, either +/+
      or +/s, without affected limbs but possibly heterozygous for the 's' gene (group
      1c); in +/+ animals with malfunctioning kidneys that lack the short-toes gene
      (group 2a) and in normal +/+ animals from different gene pools (group 2b). In all
      of the short-toes animals that expressed pathological phenotypes, the proximal
      tubule showed abnormal morphology. There was no morphological evidence of kidney
      abnormality in the siblings having normal limbs or in the group 1b axolotls
      examined. However, mesonephroi from animals (group 2a) of other gene pools that
      had ascites exhibited a different and more pronounced pathology. On the basis of
      the dramatically distinct proximal tubule pathology of the sporadic floaters, we
      conclude that this phenotype is more likely caused by infection than to a variant
      of the short-toes gene.

PMID- 18621180
TI  - Eye muscles of the pike (Esox lucius) fiber types and their actomyosin ATPase and
      SDH activity.
AB  - The eye muscles of the pike are organized in two distinct populations of fibers
      arranged in semicircular layers. The distal layer, consisting of small diameter
      muscle fibers, is mainly made up of type I and tonic (slow) fibers. The central
      and proximal (facing the eyeball) parts of the eye muscles are occupied by IIB
      and IIC (fast) fibers. As a main criterion for identification of muscle fiber
      types, the reaction for actomyosin ATPase activity has been used: metabolic
      characterization of these fibers has been carried out on the basis of SDH
      activity.

PMID- 18621181
TI  - Trichobilharzia ocellata: Quantification of effects on haemocytes of the pond
      snail Lymnaea stagnalis by morphometric means.
AB  - To identify functionally different subpopulations, we quantified by morphometric
      means the spreading activity of circulating haemocytes of the pond snail Lymnaea
      stagnalis, recognized by monoclonal antibodies (5 surface and 5 cytoplasmic). The
      influence of snail age and of the different intramolluscan stages of the
      compatible avian schistosome Trichobilharzia ocellata on this activity were
      studied. The antibody-recognized cells could be separated into two groups,
      differing in their spreading activities. The probes detecting cytoplasmic markers
      recognized the majority of cells (78-95%). These were active (well spreading),
      differentiated cells. The surface probes recognized a smaller part (12-38%) of
      the total haemocyte population. These harmocytes were less active (less
      spreading), and were predominantly immature cells. The relative sizes of the
      antibody-detected subpopulations were not affected by snail age or infection with
      T. ocellata. The maximal size (planimetric area) attained after attaching to
      glass of all cells increased between day 0 (juvenile snails) and about 6 weeks
      post (sham) exposure and then decreased. Infection had little effect on the
      spreading activity of the more differentiated cells. The less differentiated
      cells showed a larger spreading activity when the parasite was present as mother
      sporocyst and also when the digestive gland area became colonized by growing
      daughter sporocysts.

PMID- 18621182
TI  - The morphology and chemistry of the scales of the orange roughy and the smooth
      and spiky oreo dories.
AB  - Proton and deuteron microprobes were used to establish the two-, and three
      dimensional patterns of calcium, fluorine, carbon and oxygen variation in the
      scales of the orange roughy (Hoplostethus atlanticus) smooth oreo dory
      (Pseudocyttus maculatus) and spiky oreo dory (Neocyttus rhomboidalis).

PMID- 18621183
TI  - Sustained primary culture of lobster (Panulirus argus) olfactory receptor
      neurons.
AB  - Appropriate conditions were developed for primary sustained culture of olfactory
      neurons of the spiny lobster Panulirus argus. Neurons were cultured in a modified
      Liebowitz L15 media supplemented with Panulirus salts, basic minimal essential
      (BME) vitamins, L-glutamine, low dextrose, and either fetal calf serum (FCS) or
      lobster haemolymph. Neurite outgrowth and cell viability was strongly affected by
      choice of adherent substratum, presence of serum, and length of animal captivity.
      Neither nerve growth factor 7s (NGF-7s), HEPES, nor preconditioned media from the
      target organ, the olfactory lobe, had any gross effect on either longevity or
      neurite outgrowth. Five morphologically distinct neuronal cell types (8-16 mum
      soma diameter) could be defined based on their number and type of processes. All
      of these cells were electrically excitable (N = 50), and many (56%) produced
      either inward or outward currents in response to stimulation with single odors.
      The proportion of cells responding to odors increased (80%) when 10 cells were
      sequentially presented with a series of 3-5 odors. The finding that cultured
      cells maintain responsiveness to odors yet are morphologically more compact than
      their counterparts in situ, argues for the prospect of using these dissociated
      cultured olfactory receptor neurons to study signal transduction in olfaction.

PMID- 18621184
TI  - Tegumental glands in a copepod Hemidiaptomus ingens: Structural, ultrastructural
      and cytochemical aspects.
AB  - Segmental tegumental glands in the calanoid copepods Hemidiaptomus ingens
      provinciae release secretions through pores which are located near the glands.
      These pores exhibit a partitioned structure. Ultrastructurally, all glands
      present a syncytial organization and are characterized by a highly developed
      Golgi apparatus and secretory grains with a heterogeneous structure. Cytochemical
      tests show that the grains are composed mainly by highly reactive polysaccharides
      associated with protein granulations alternating with slightly, if at all,
      reactive polysaccharides. The role of these secretions is still unclear.

PMID- 18621185
TI  - The eggshell of the cherry fly Rhagoletis cerasi.
AB  - One of the major pests in Greek cherry orchards is the cherry fly Rhagoletis
      cerasi (Diptera: Tephritidae). In order to complete our comparative work on the
      chorion assembly of other representatives of the fruit flies (e.g. Ceratitis
      capitata and Dacus oleae) we studied eggshell morphogenesis in the cherry fly.
      The oocyte is surrounded by several distinct layers which are produced during
      choriogenesis. The eggshell consists of the vitelline membrane, a fibrous layer
      of possible water-proofing function, an innermost chorionic layer, endochorionic
      and exochorionic layers. The endochorion shows a branched configuration with
      irregular cavities, and the exochorion consists of inner and outer layers for
      better embryo protection. At the anterior region of the follicle, the hexagonal
      borders of the follicle cells are created by endochorionic material, covered by
      both inner and outer exochorion. This area resembles the D. melanogaster
      chorionic appendages and therefore can serve for plastron respiration. The
      structural results support the phylogenetic relationships among the tephritids
      (Rhagoletis is closer to Ceratitis than Dacus). The presence of peroxidase in the
      endochorion, detected by diaminobenzidine, is consistent with the eggshell
      hardening at the end of choriogenesis, following the same pattern with the other
      fruit flies studied so far. Two major chorionic proteins are found both in R.
      cerasi and in C. capitata and therefore general conclusions can be drawn from
      this study, concerning the pattern of choriogenesis, which all dipteran insects
      follow, in order to create a resistant and functional eggshell, and the high
      conservation of the proteinaceous components of the chorion among species in the
      order.

PMID- 18621186
TI  - Effects of buprofezin on the ultrastructure of the third instar cuticle of the
      insect Trialeurodes vaporariorum.
AB  - Treatment with buprofezin at the beginning of the third instar of Trialeurodes
      vaporariorum results in death of the larvae at the time of moulting. Electron
      microscopic observations, after treatment of the larvae with 20 mg a.i./l
      buprofezin, does not reveal any difference in the ultrastructural profile before
      apolysis, however formation of a normal lamellate procuticle is disturbed. The
      pharate procuticle is amorphous, varying in thickness and the mean thickness is
      greatly reduced. The subcuticle is interrupted several times at locations
      corresponding with the thinnest places of the pharate cuticle. Epidermal cells
      contain unusual structures such as myelin figures and hypertrophied mitochondria
      indicating that buprofezin may have an additional toxic effect on epidermal
      cells.

PMID- 18621187
TI  - Development of muscle fibre nuclei in holometabolous insect larvae.
AB  - The growth and development of the nuclear population from intersegmental dorsal
      longitudinal muscles (IDLM) of Bombyx mori and Pieris brassicae during larval
      development were studied. Using whole muscle mounts, examined with an image
      analysis system, we observed increases in muscle size but a constant number of
      fibres and concomitant increases in the number and size of fibre nuclei. The
      gradual growth of the nuclei throughout larval life, corresponding very probably
      to an increase in their DNA content, is unequal and results in heterogeneity of
      the nuclear population. This suggests periodic incorporation of myoblasts into
      the larval muscles; the nuclei arising from these myoblasts would therefore
      undergo endomitotic processes and grow polyploid. The possibility of somatic
      reduction divisions of the polyploid muscle nuclei is discussed.

PMID- 18621188
TI  - Localization of catecholamine-containing nerve fibres in the branchial heart and
      cardiac ganglion of the common cuttlefish Sepia officinalis L. (cephalopoda).
AB  - The innervation of the branchial heart of Sepia officinalis was examined using
      TEM and glyoxylic acid induced fluorescence. In the cardiac ganglion and in
      cardiac nerves bluish-green fluorophores were seen associated with perikarya and
      varicose nerve fibres. Microspectrofluorometric analysis provided clear evidence
      that monoaminergic neurons in the branchial heart contain only catecholamines.
      Considering pharmacological data, it is more than likely that 5-hydroxytryptamine
      (serotonin) is not present in this system.

PMID- 18621189
TI  - Morphogenesis of the antenna of the male silkmoth. Antheraea polyphemus, III.
      Development of olfactory sensilla and the properties of hair-forming cells.
AB  - During adult development of the male silkmoth Antheraea polyphemus, the anlagen
      of olfactory sensilla arise within the first 2 days post-apolysis in the antennal
      epidermis (stage 1-3). Approximately on the second day, the primary dendrites as
      well as the axons grow out from the sensory neurons (stage 4). The trichogen
      cells start to grow apical processes approximately on the third day, and these
      hair-forming 'sprouts' reach their definite length around the ninth day (stages 5
      6). Then the secretion of cuticle begins, the cuticulin layer having formed on
      day 10 (stage 7a). The primary dendrites are shed, the inner dendritic segments
      as well as the thecogen cells retract from the prospective hair bases, and the
      inner tormogen cells degenerate around days 10/11 (stage 7b). The hair shafts of
      the basiconic sensilla are completed around days 12/13 (stage 7c), and those of
      the trichoid sensilla around days 14/15 (stage 7d). The trichogen sprouts retract
      from the hairs after having finished cuticle formation, and the outer dendritic
      segments grow out into the hairs: in the basiconic sensilla directly through, and
      in the trichoid sensilla alongside, the sprouts. The trichogen sprouts contain
      numerous parallel-running microtubules. Besides their cytoskeletal function,
      these are most probably involved in the transport of membrane vesicles. During
      the phase of cuticle deposition, large numbers of vesicles are transported
      anterogradely from the cell bodies into the sprouts, where they fuse with the
      apical cell membrane and release their electron-dense contents (most probably
      cuticle precursors) to the outside. As the cuticle grows in thickness, the
      surface area of the sprouts is reduced by endocytosis of coated vesicles. When
      finally the sprouts retract from the completed hairs, the number of endocytotic
      vesicles is further increased and numerous membrane cisterns seem to be
      transported retrogradely along the microtubules to the cell bodies. Here the
      membrane material will most probably be used again in the formation of the
      sensillum lymph cavities. Thus, the trichogen cells are characterized by an
      intensive membrane recycling. The sensillum lymph cavities develop between days
      16-20 (stage 8), mainly via apical invaginations of the trichogen cells. The
      imago emerges on day 21.

PMID- 18621190
TI  - The development of branched silk gland nuclei.
AB  - Nuclei in the giant polyploid silk gland cells of Calpodes ethlius grow by
      endomitosis and can develop hundreds of branches during larval life. The shape of
      the these nuclei is characteristic for each region of the gland. We have found
      shape to be correlated with arrangement of the nuclear matrix. Scanning electron
      microscopy showed nuclear matrices with shapes similar to those of feulgen
      stained nuclei. Profiles of isolated matrices seen by transmission electron
      microscopy had filaments aligned parallel to the long axis of nuclear branches.
      DNA stained by Hoechst had a similar parallel alignment within the branches.
      Nuclear shape may be maintained by a small number of components, since
      electrophoretic analysis showed only a few abundant polypeptides in the matrix
      fraction. Silk gland nuclei have some of the same nuclear matrix antigens found
      in smaller, more regularly shaped, eukaryote nuclei.

PMID- 18621191
TI  - Ultrastructure of sperm cells in the female gonoduct of Xiphinema.
AB  - The ultrastructure of the sperm cells in the female gonoduct of the nematodes
      Xiphinema theresiae and X. pinoides is described. The nucleus of the sperm cells
      is composed of several electron-dense clumps of chromatin that is not surrounded
      by a nuclear envelope. A layer of mitochondria, in which the mitochondrial
      cristae are only rarely visible, lies around the nuclear material. In the
      surrounding cytoplasm packets of electron-dense fibres are abundant. The sperm in
      the uterus have the following surface differentiations: highly intertwined
      protrusions between adjacent sperm cells, protrusions coinciding with the
      plication of the inner uterine wall and a slightly undulated surface towards the
      uterine lumen. It is argued that in the uterus, the sperm cells actively move in
      proximal direction by a mechanism resembling pseudopodial movement, in which the
      packets of fibres are involved. In the oviduct, the sperm cells loose their
      surface protrusions and the packets of fibres gradually become less abundant.
      Since the oviduct has no pre-formed lumen, the sperm cells appear to wedge their
      way along by forcing oviduct cells apart.

PMID- 18621192
TI  - Ultrastructural studies on accessory nuclei in developing oocytes of the
      crustacean, Siphonophanes grubei.
AB  - Numerous accessory nuclei (AN) occur within peripheral cytoplasm of Siphonophanes
      grubei oocytes. They exhibit typical nuclear structure, with double membrane
      envelope pierced by pore complexes. Although no explicit evidence was shown,
      indirect arguments exist indicating that AN originate from the oocyte nucleus.
      Presence of clumps of DNP material within AN suggests that AN might play some
      role in amplified DNA metabolism. Participation of AN in cellular membrane
      elaboration is also postulated.

PMID- 18621193
TI  - Effects of osmotic shock on the ultrastructure of cell nuclei in euryhaline and
      stenohaline crustaceans.
AB  - Changes in cell ultrastructure in relation to volume regulation following
      application of osmotic challenges have been but poorly documented up to now. In a
      previous study, we demonstrated that large and immediate changes in the
      organization of nuclear chromatin occur in mammalian cells under such conditions.
      Similar chromatin modifications are shown in the present study in the cells of
      the stenohaline crab Maia verrucosa. They are not seen in the cells of the
      euryhaline species tested, hyperosmoregulating (Eriocheir sinensis) or
      osmoconforming (Cancer pagurus). Nor are they seen in cells of Portunus puber,
      another stenohaline species. These results are discussed in the context of the
      disrupting effects that inorganic ions have on macromolecular structures and of
      the protection which may be conferred by organic osmolytes used by various
      crustacean species.

PMID- 18621194
TI  - Isolation of third, fourth, and fifth instar larval midgut epithelia of the moth,
      Trichoplusia ni.
AB  - A new tissue isolation technique was used to create intact midgut epithelial
      wholemounts from three Trichoplusia ni (Lepidoptera: Noctuidae) larval instars.
      The protease, dispase, removed the basal lamina and associated connective tissue
      and allowed for high resolution light microscopy of entire epithelia. Columnar,
      goblet, differentiating, and stem cells were characterized by double fluorescent
      labelling of f-actin and nuclei. A comparison of cell populations by digital
      image analysis revealed significant regional and temporal changes in the density
      and number of differentiating and stem cells. Growth of the midgut epithelium
      from third to fourth instar, and from fourth to fifth instar, was accomplished by
      both cell differentiation and cell division. Cell division however, was greatly
      reduced from fourth to fifth instar with a concomitant sharp decrease in the stem
      cell population.

PMID- 18621195
TI  - Structural and ultrastructural analysis of gills and gut of Hexagenia rigida
      nymphs (ephemeroptera) in relation to contamination mechanisms.
AB  - In the context of an experimental approach to organic and inorganic mercury bio
      accumulation by burrowing mayfly nymphs-Hexagenia rigida-, gills and different
      parts of the gut were investigated by light and electron microscopes. In the gut,
      two regions were studied: (1) mesenteron (midgut) characterized by cells with
      microvilli and a peritrophic membrane throughout this part, a lot of fungal
      hyphae being found on it; (2) proctodeum (hindgut) characterized by macrovilli,
      the apical face of cells being covered by a thick layer of chitin; many bacteria
      were observed at the bottom of macrovilli. The stomodeum (foregut) is extremely
      short. The gills are made up of six pairs of lamellae fringed with long filaments
      which are arranged on both sides of the long axis. Gills are constituted by
      tracheae and tracheoles, with a large canal for haemolymph circulation; muscle
      masses and nerve bundles were also observed. This structural approach shows that
      the nymph interface with the external environment, at gill and gut barrier
      levels, are quite different. Links between this structural and ultrastructural
      analysis and contamination mechanisms, via the trophic or direct route, are
      discussed; gills and gut could be transfer routes for mercury absorption, but
      also target organs for metal accumulation.

PMID- 18621196
TI  - Ultrastructure and permeability characteristics of the membranes of mucous
      granules of the hagfish.
AB  - Mucous granules secreted by the slime glands of the hagfish. Eptatretus stouti,
      were studied after ultrarapid cryofixation and freeze substitution in diverse
      media (osmium tetroxide in acetone; several aqueous glutaraldehyde-based media
      with or without osmium). Only freeze substitution with osmium tetroxide-acetone
      preserved the granules intact, allowing visualization of its single unit
      membrane. Tests of the rupture or stability of freshly secreted mucous granules
      in sea water and other aqueous media showed the membranes of the granules are
      permeable to all inorganic cations tested, ranging in relative mass from ammonium
      to barium. They are permeable to the univalent anions chloride, nitrate, and
      bicarbonate, but not to the di- or trivalent anions sulfate, phosphate, and
      citrate. Moreover, in solutions where nonpenetrant anions were present, rupture
      occurred if the osmotic pressure was below a critical level (about 800 mOsmol/l).
      The structural and permeability characteristics of the granules account for the
      explosive speed with which they rupture, releasing their mucous contents, on
      contact with sea water.

PMID- 18621197
TI  - Ring-shaped organization of cytoskeletal F-actin associated with surface sensory
      receptors of Schistosoma mansoni: a confocal and electron microscopic study.
AB  - The surface syncytial epithelium of the human blood fluke, Schistosoma mansoni,
      contains numerous ciliated or unciliated, bulb-shaped sensory receptors. At the
      ultrastructure level, sensory receptors with similar topographic and
      morphological structures have been found in the epithelial surface layers of all
      known species of schistosomes and other species of flatworm parasites. Although
      many studies have focused on the syncytial cytoskeleton of schistosomes, while
      some other studies have examined the fine structures of the syncytial sensory
      receptors, no-one has demonstrated the association of cytoskeletal elements with
      the surface sensory cells except the well-known microtubules associated with
      ciliated structures. The present study, using confocal laser scanning microscopy
      combined with scanning and transmission electron microscopies, demonstrates the
      association of ring-shaped F-actin within the epithelial sensory receptors. The F
      actin rings can be characterized into two types according to their size, density,
      and distribution. The actin rings found in the syncytia of both the male and
      female schistosomes appear to be more dense and larger in size than the actin
      rings located only at the central regions of the tuberculated structures of the
      male dorsal syncytium. Our observation of F-actin rings associated with the spine
      bearing tubercles, combined with the results obtained from other ultrastructural
      investigations, also indicate the presence of the unciliated sensory receptors in
      each tuberculated structure of the male dorsal surface syncytium, which have not
      been reported in other studies on schistosome epithelial sensory cells.

PMID- 18621198
TI  - Cell junctions in the gut of Protura.
AB  - The main cell junctions in the intestinal tract of a small group of apterygotan
      insects, Protura, were examined in conventional thin sections, tracer-infiltrated
      sections and freeze-fracture replicas. The smooth septate junctions in the midgut
      of collembolan Tomocerus minor were also studied for comparison. Pleated septate
      junctions are found in foregut, hindgut and Malpighian papillae. They exhibit
      regular septa crossing the intercellular clefts in thin sections; and the septa
      with a pronounced zig-zag appearance run parallel to form a honeycomb structure
      in tracer-impregnated sections. After freeze-fracture undulating rows of
      intramembranous particles (IMPs) are visible on the P face. Smooth septate
      junctions are observed in the midgut. The intercellular septa often run in pairs
      for long tracts and exhibit a wavy course in lanthanum impregnated sections. The
      IMPs exhibited on the E face are usually separated one from another. Twin
      arrangement of particle rows is also apparent on the replicas. Gap junctions are
      frequent in both the midgut and hindgut and possess the conventional
      characteristics of 'inverted gap junction' with E face connexons. These results
      provide further evidence relating Protura closely to Collembola as well as to
      primitive arthropods.

PMID- 18621199
TI  - Origin and development of the tergotrochanteral muscle in Chironomus (Diptera:
      Nematocera).
AB  - The origin and the development of the tubular tergo-trochanteral muscle (TTD) was
      studied by light and electron microscopy in Chironomus (Diptera: Nematocera).
      Unlike the flight muscles, the TTD was found to develop from myoblasts located
      around a larval axon, without contribution from a larval muscle. The myoblasts
      fuse together to form myotubes. Innervation of the TTD arises from the larval
      axon. The myotubes send out sarcoplasmic extensions towards the axon branches
      issued from the larval axon. The first differentiated synapses are described. The
      TTD begins to grow later than the flight muscles. The implications of this
      developmental lag are discussed.

PMID- 18621200
TI  - Structure of the female genital glands of the oviduct in the opisthobranch
      mollusc, Runcina.
AB  - Runcina is a small hermaphroditic opisthobranch which possesses a monaulic
      reproductive system. In previous studies the male copulatory apparatus, the
      structure of the spermatophore and also the process of oogenesis have been
      described. The present paper gives an account of the ultrastructure of the female
      genital glands of the oviduct. In Runcina the oviduct comprises three primary
      regions, the albumen gland, the egg capsule gland and the mucous gland. Eggs
      enter the fertilization chamber and as they pass the opening of the albumen gland
      they become surrounded by albumen or perivitelline fluid. The eggs appear to
      become encapsulated as they traverse the egg-capsule gland and are eventually
      stuck together by mucus to form an egg mass. The epithelial lining of the three
      glands consists of alternating ciliated and secretory cells. The characteristics
      in secretory products of the glandular cells are described, and are discussed
      with reference to the way they contribute to egg vestment.

PMID- 18621201
TI  - Ultrastructure of the tube-foot of an ophiuroid echinoderm, Hemipholis elongata.
AB  - The morphology of the tube-foot of the brittlestar, Hemipholis elongata was
      examined by transmission and scanning electron microscopy. The entire surface of
      the tube-foot is covered by microvilli and a thick cuticle layer. At the tip of
      the tube-foot the cuticle layer is thinner and sensory-secretory complexes are
      seen. These are composed of two secretary cells and a central ciliated sensory
      cell. Scanning electron microscopy shows that the cilium which extends from the
      receptor cell ends flush with the surrounding microvilli. These studies suggest
      that the tube-feet in ophiuroids are important structures in sensory-reception,
      gas-exchange as well as locomotion. The hemoglobin containing cells within the
      lumen of the tube-feet may serve in oxygen transport and storage.

PMID- 18621202
TI  - Initial stages of tunic morphogenesis in the ascidian Halocynthia: a fine
      structural study.
AB  - Tunic morphogenesis in embryos of the ascidian Halocynthia roretzi was examined
      by scanning and transmission electron microscopy. For this purpose it was
      necessary to modify the classical embedding procedure. Soon after reaching the
      initial tail-bud stage, tunic deposition is initiated on the dorsal side of the
      embryo. As soon as the embryo is completely covered by the tunic, larval fins are
      formed. The test cells settle onto the embryo. At this stage only the outer
      cuticle and the outer tunic compartment have appeared. Tunic morphogenesis is
      accompanied by ultrastructural modifications of the epidermis characteristic of
      secreting cells. Cytochemical investigations reveal polysaccharide glycogen-like
      material in the lumen of epidermal lacunae and in the outer compartment of the
      tunic. Our observations strongly suggest that this material is stored in the
      lacunae and discharged into the outer compartment. The significance of fluffy
      osmiophilic material that appears at the early tail-bud stage and enlaces the
      whole embryo is discussed.

PMID- 18621203
TI  - Oocytes degeneration in the queen honey bee after infection by Nosema apis.
AB  - Terminal oocytes containing yolk in both healthy and nosema infected queen honey
      bees were studied. In the healthy queens the terminal oocytes exhibited a layer
      of follicular cells which were covered by a smooth-surfaced ovariole sheath. In
      the ooplasm were numerous electron-dense yolk granules and lipid yolk droplets.
      The elecron-dense yolk granules exhibited a crystalline structure. Stacks of
      endoplasmic reticulum were observed in the yolk granules throughout the ooplasm.
      Numerous mitochondria possessing well defined cristae were also observed. Oocytes
      in the ovary of queen honey bees appeared degenerated after 7 days of infection
      by Nosema apis. The ovariole sheath was wrinkled. In the ooplasm, yolk granules
      were broken down into small spheres and granular substances. Numerous ribosomes
      without stacks of endoplasmic reticulate were observed. Lysosomes were abundant
      and numerous electron-dense materials surrounded by a membrane were detected. The
      oocytes appeared to be extensively autolysed. The significance of these
      observations is discussed.

PMID- 18621204
TI  - Fine structure of the rectal pads in the desert locust Schistocerca gregaria with
      reference to the mechanism of water uptake.
AB  - The rectal pads of Schistocerca gregaria are composed of three different cell
      types: epithelial, secondary and junctional cells. The rectal pads are
      interconnected by simple rectal cells and both are lined internally by a
      articular intima. The epithelial cells exhibit extensive infoldings of the apical
      plasma membranes that are closely associated with mitochondria. Their lateral
      plasma membranes are highly folded around large mitochondria and enclose
      intercellular channels and spaces. They are united by belt and spot desmosomes,
      septate junctions, gap junctions and scalariform junctions, but terminate in a
      basal syncytium without contacting the basal plasma membranes. The apical and
      basal cytoplasm contain coated vesicles, dense tubular elements, multivesicular
      bodies and lysosomes, suggesting receptor-mediated endocytosis of small peptide
      molecules into the epithelial cells. The apical membrane infoldings of the
      secondary cells are also associated with large mitochondria. Their basal plasma
      membranes are covered by connective cell processes and connected with them by
      spot desmosomes which may be involved in solute recycling. The presence of
      neurosecretory-like axons near the secondary cells suggests that they exert local
      control on the function of these cells. The ultrastructural details are examined
      in relation to their role in solute and water transport.

PMID- 18621205
TI  - Characteristics and development of the tyrosine-rich protein granules in the
      adipose tissue of the Curculionid beetle Sitophilus oryzae.
AB  - In the Curculionid beetle Sitophilus oryzae, the fat body is composed of one type
      of adipocyte, interstitial cells and oenocytes. Synthesis and storage of tyrosine
      rich-protein granules (TRPG) in adipocytes are observed during all the larval and
      prepupal stages (except the first larval instar which has not been studied). They
      appear first in the posterior part of the fat body, around the nucleus of
      adipocytes. They progressively invade the cytoplasm. In the young pupa, TRPG are
      present in every part of the body, including the head and the appendages in
      formation. TRPG grow in size by fusing together. Their mean diameter is 6 microm,
      but some of them reach up to 50 microm. They present a basic core and an acidic
      periphery. Their charge in tyrosine increases until the prepupa. They are APS and
      lipid negative and contain no RNA. During metamorphosis they take on a
      reticulated structure, evoking a golf ball, and disintegrate into small granules,
      the tyrosine content of which diminishes drastically, especially in contact with
      epidermal cells, whence tyrosine is probably transferred. TRPG in S. oryzae
      contain 16 different insoluble proteins. Five of them are tyrostaurins
      characterized by their very high content in tyrosine (up to 27%) and their strict
      insolubility in aqueous solution. Arylphorin-like proteins have not been detected
      in S. oryzae granules.

PMID- 18621206
TI  - Immunocytochemical localization of FMRFamide in the central nervous system and
      the kidney of Helisoma duryi (Mollusca): its possible antidiuretic role.
AB  - The distribution of FMRFamide-immunoreactive neurons in the central nervous
      system of the freshwater pulmonate, Helisoma duryi is described. All parts of the
      central nervous system except the two pleural and the right parietal ganglia,
      contain immunoreactive neurons. By immunogold techniques, only one kind of
      neurosecretory FMRFamide-immunoreactive cell (previously identified as the type-3
      cell) was localized in the visceral and left parietal ganglia. This cell type has
      been previously implicated in an antidiuretic role. FMRFamide-immunoreactive
      material is found in the whole mount of the kidney as well as in kidney sections.
      Electron microscopic examination shows that the axons innervating either the
      smooth muscles of the kidney or the kidney itself contain neurosecretory granules
      morphologically similar to type-3 cells of the visceral and left parietal
      ganglia. When incubated in saline containing nanogram quantities of FMRFamide,
      the wet weight of the kidney increased. It is suggested that FMRFamide-like
      substance may function as an antidiuretic factor and that the kidney is a target
      organ of this peptide for osmoregulation.

PMID- 18621207
TI  - Relationships between cell size and nuclear morphology in crayfish neurons.
AB  - The morphology and ultrastructure of cell nuclei in neurons of the third
      abdominal ganglion of crayfish were studied from alternating series of ultrathin
      and semithin sections. The ganglion contains approximately 850 neurons with sizes
      between 10 and 200 microm. Cell nuclei show a great variability. Their size, the
      chromatin distribution, the number of nuclear pores, the degree of nucleolar
      segregation and the size of nucleolus vary in close relationships with the cell
      size.

PMID- 18621208
TI  - Ciliary specializations in branchial stigmatal cells of protochordates.
AB  - Tissues from the pharynx of five representative species of the protochordates
      (subphylum Tunicata, the three classes Ascidiacea, Thaliacea and Appendicularia,
      and subphylum Cephalochordata) were examined in both thin sections and freeze
      fracture replicas. In all species, the stigmatal cilia of the branchial chamber
      are neatly arranged and move continuously to propel sea-water in a fixed
      direction for respiration and feeding of the organism. A number of
      specializations are found in the basal region of these cilia and are represented
      by: a) bridges connecting axonemal doublets numbers 5 and 6; b) dense fibrous
      material linking the doublet microtubules of the axoneme to the ciliary membrane,
      sometimes in the shape of longitudinal strands or as clusters of filaments; c)
      intramembrane particles (IMPs) associated with the P-face of the membrane, often
      arranged in clusters evenly aligned along the ciliary shaft in relation to the
      underlying axonemal doublets. Ciliary specializations are distributed along the
      plane of the effective stroke of the beat in both the ascidian Botryllus
      schlosseri and in the thaliacean Pyrosoma atlanticum and the amphioxus
      Branchiostoma lanceolatum, whereas in the thaliacean Doliolum nationalis and the
      appendicularian Oikopleura dioica a more uniform distribution of these
      specializations all around the basal portion of the cilia is observed. Whatever
      the disposition of the ciliary specializations in all the examined species, they
      are always present at the base of the water-propelling cilia. Some morphological
      evidence suggests that these specializations play a mechanical function in
      tethering the ciliary membrane to the axoneme. We propose that they help maintain
      the orientation of the cilia during beating, enhance their stiffness and improve
      their efficiency.

PMID- 18621209
TI  - 'Plywood' structure and mineralization in the scales of the ocean sunfishes, Mola
      mola and M. ramsayi.
AB  - The mineralized dermal denticles of fibrillar structure of the dermal plate of
      the modified scales of Mola mola and Mola ramsayi have both highly specialized
      and archaic features suggesting that the Molidae branched from the teleost line
      at an early stage in its evolution.

PMID- 18621210
TI  - The structure and growth rates of the cuticle of the stick-insect Heteropteryx
      dilatata.
AB  - Locust-style and pseudo-orthogonal structures were found in the cuticle of
      Heteropteryx dilatata, with the tibiae and femora containing both, and the ocular
      facets showing only helicoidal construction. The same epidermal cells appear to
      be competent to secrete both locust-style and pseudo-orthogonal cuticle
      structure. Curved fibres were found to exist and an apparent 'diagonal lattice'
      construction of the fibres in the thoracic and abdominal tergites and sternites
      at about 45 degrees to the insect's long axis. The advantages of flight have
      apparently been sacrificed for increased 'armour-plating' and the wings exhibit
      the characteristics of flightlessness. The minimum age post final moult of the
      insect as calculated from the growth layers was 7 weeks, the actual age being
      unknown. 'Trauma lines' and 'continuous lamellation' were seen and several
      possible explanations discussed.

PMID- 18621211
TI  - Liquid crystal order and turbulence in the planar twist of the growing plant cell
      walls.
AB  - During growth, the plant cell wall behaves as a dynamic structure that
      exemplifies a case of unstable balance between a capability to organize a
      characteristic order and a permanent tendency to destroy the order. This
      interpretation allows previous results to be complemented and reappraised; it
      also integrates the cell wall behavior into a unified frame. The wall thickenings
      are structured according to a crystal-like pattern (cholesteric mesophase).
      Laminar helicoids are locally deposited on cell facets and form actual flat and
      planar twists in which the causes of topological defects are minimized. The
      helicoidal pattern is short-lived and its occurrence results from a complex
      interplay between self-assembly and disassembly properties. Two alternative
      processes destroy this critical state: 1. Externally, the surface extension which
      produces a progressive degradation and a randomization by shearing and
      stretching; 2. Internally, aleatory and punctual instabilities which alter the
      genesis of the system at the plasmalemma/wall interface. As the time goes on, the
      twisting either resumes or, in contrast, the perturbation increases. The system
      tends to become unpredictable thus suggesting turbulence.

PMID- 18621212
TI  - Junctional complexes between the Sertoli cells in the testis of the
      crayfish,Procambarus paeninsulanus.
AB  - The testis of the crayfish,Procambarus paeninsulanus, was prepared for light and
      electron microscopic study. It is composed of tubules containing germ
      spermatogenic and somatic-Sertoli cells. In sections of tubules lacking sperm,
      the Sertoli cells rest on the basement membrane. A desmosome-like junction is
      found near the luminal surface between two adjacent Sertoli cells. It is closely
      associated with a long, septate junction. Between Sertoli cells which have
      surrounded numerous spermatids, the undulating membranes exhibit profiles of
      pleated septate junctions in tangential sections. The morphology of the pleated
      septate junctions between adjacent Sertoli cells suggests a possible role as a
      permeability barrier.

PMID- 18621213
TI  - Intestinal cell types in the freshwater snail planorbarius corneus:
      Histochemical, immunocytochemical and ultrastructural observations.
AB  - The intestinal cell types of the pulmonate gastropodPlanorbarius corneus were
      studied using histochemical, immunocytochemical and ultrastructural procedures.
      Supporting cells, mucous cells and gland cells were observed in the intestine
      epithelium. The supporting cells seem to be involved in absorption process,
      showing endocytosis vesicles, evidence of lysosomal activity and storage of
      reserve materials. The presence of epithelial cells specialized in secretion
      indicates that digestive enzymes may be produced. Indeed, immunoreactive alpha
      amylase molecules have been demonstrated. Some gland cells showed the
      ultrastructural features of invertebrate and vertebrate enteroendocrine cells and
      were also positive to vertebrate anti-insulin, anti-gastrin and anti-serotonin
      antibodies.

PMID- 18621214
TI  - Peculiarities of the organization of egg chambers in carabid ground beetles and
      their phylogenetic implications.
AB  - The ovaries of 31 species of the coleopteran familyCarabidae have been studied by
      light and electron microscopy. Ovarioles of all the examined insects are of the
      polytrophic type. In the majority of the species a constant number of nurse cells
      per egg chamber has been observed. However, several species do not obey the 2(n)
      rule and the number of nurse cells varies considerably even in the consecutive
      egg chambers of the same ovariole. In spite of the differences, the number of
      intercellular bridges connecting nurse cells to the oocyte is fixed and species
      specific. InCarabidae seven types of egg chambers have been characterized
      regarding the number of divisions, the number of nurse cells and the way the
      nurse cells are bridged to the oocyte. Some phylogenetic implications are
      considered.

PMID- 18621215
TI  - Ultrastructural diversity in the pore canal systems of amphipod crustaceans.
AB  - Transmission electron microscopy was used to analyze the structure and
      organization of the intracuticular pore canal system in 34 species of amphipod
      crustaceans. Pore canals were detectable in all species, including those that,
      from scanning electron microscopy, had been considered to lack them. Canal
      structure ranges from simple transcuticular passages of uniform diameter to more
      elaborate systems with distal canal dilatations variously equipped with electron
      dense collars, tubular filaments, single or multiple channels leading to the
      surface and transverse partitions separating canal contents of different electron
      densities. Considerable branching between tubular elements of the canal system is
      evident in many species. In most species the canals communicate with the
      outsidevia epicuticular channels. Even in those species in which this
      communication was not established, their epicuticle generally contains abundant
      cavities with external pores. Although some consistency in structure and
      organization is present among a few groups of taxonomically related species, pore
      canal characteristics generally could not be correlated with habitat or life
      style. It is suggested that the structural and organizational variety present
      reflects a considerable array of functions among amphipod pore canal systems.

PMID- 18621216
TI  - Ultrastructure of the spermatozoon ofElenchus japonicus and its bearing on the
      phylogeny of strepsiptera.
AB  - The fine structure of the mature spermatozoon of the strepsipteranElenchus
      japonicus Esaki and Hashimoto (Elenchidae) is described using transmission
      electron microscopy. The spermatozoon was seen to have an elongated head, a tail
      containing a 9 + 9 + 2 axoneme, two mitochondrial derivatives and two accessory
      sheaths. The monolayered acrosome is conical in shape while the nucleus exhibits
      an internal channel of uncondensed chromatin. The tail is long, and in its final
      portion, the axoneme, loses its elements progressively. These results are
      compared with the sperm ultrastructure ofXenos moutoni De Buysson (Stylopidae)
      and with those of other insect orders, particularly the Coleoptera.

PMID- 18621217
TI  - A comparative study of digestion in a raptorial ciliate and in the facultative
      carnivorous form of a filter feeding ciliate.
AB  - Digestion in the carnivorous form (giant) of the filter feeding ciliateOxytricha
      bifaria and in the obligatory carnivorous, raptorial feeding ciliateLitonotus
      lamella were studied and compared at the ultrastructural level. It was found that
      whenO. bifaria, shifts from the normal, bacterivorous to the gigantic carnivorous
      form, it modifies its morphology, acquiring new and more effective feeding
      devices but maintaining unaltered the digestion pattern and mode of food
      absorption. This takes place through pinocytotic activity at the food vacuolar
      membrane. The digestive process inLitonotus is far more rapid: within 10 min the
      vacuolar membrane disappears; in this way the cytoplasm of the prey, not yet
      completely digested, is mixed with that of the predator and a pinocytotic
      mechanism does not seem to he necessary for nutrient assimilation. In general,
      results demonstrate that filter feeders and raptorial ciliates differ not only in
      their food intake mechanism, but also in the pattern and the timing of their
      digestive process, even when they ingest similar kinds of food.

PMID- 18621218
TI  - Entry of algal symbionts into oocytes of the coral Litophyton arboreum.
AB  - On the Red Sea coral reefs Litophyton arboreum is a common octocoral whose
      endodermal cells are associated with endosymbiotic dinoflagellates
      (zooxanthellae). Colonies of this species are gonochoric and brood planulae
      which, upon release, are already associated with the algal symbionts. Algal cells
      within membrane-bound vacuoles are observed within the gastrovascular cavity of
      the polyps, adjacent to the oocytes and are gradually phagocytized by the
      follicular cells which surround the oocytes. During oogenesis, temporary gaps
      open in the mesoglea underlying the follicular cells. Symbionts within vacuoles,
      along with cytoplasm and various organelles derived from the follicular cells,
      are translocated through these gaps. Subsequently, groups of zooxanthellae
      accumulate at the perioocytic zone, flanked between the mesoglea and oocytic
      microvilli. At a later stage, prior to the commencement of the breeding season,
      symbionts pass through the oolemma and rest inside the periphery of the oocytes.
      It is proposed that early uptake of zooxanthellae by sexual progeny at the oocyte
      stage, indicates a highly specialized mode of interaction between this algal
      symbiont and its host.

PMID- 18621219
TI  - Actin filaments associated with the basal Sertoli cell surface in the alligator
      and turtle.
AB  - We have studied, using electron microscopy, the basal cytoplasm of Sertoli cells
      in the alligator (Alligator mississippiensis) and the turtle (Pseudemys scripta).
      Filament bundles occur immediately adjacent to the basal plasma membrane. The
      diameter of these filaments is smaller than that of perinuclear intermediate
      filaments, but is similar to that of filaments present in peritubular cells. In
      the alligator, the filament bundles appear to form a branching network over the
      base of the cell and are related to cisternae of the endoplasmic reticulum. In
      the turtle. filaments occur either in distinct bundles within folds of the plasma
      membrane or as a more uniform layer over the base of the cell. In fixed frozen
      sections, labelled with rhodamine phalloidin, linear bands of fluorescence occur
      in regions which correspond to those containing the filament bundles observed by
      electron microscopy. We conclude that the basal filaments in alligator and turtle
      Sertoli cells are actin and speculate that these filaments may be involved in
      cell/substratum adhesion.

PMID- 18621220
TI  - Endocrine cells and nerves in the stomach of the lizard Podarcis hispanica
      detected by immunocytochemistry.
AB  - The general identification of endocrine cells in the stomach of the lizard
      Podarcis hispanica was carried out by their response to the Grimelius and Masson
      Fontana techniques. 11 immunoreactive cell-types, positive for chromogranin-,
      serotonin-, caerulein/gastrin/ cholecystokinin (CAER/G/CCK)-, glucagon-like
      peptide-1 (GLP-1)-. glucagon-, bombesin-,somatostatin-, pancreatic polypeptide
      (PP)-, peptide tyrosine tyrosine (PYY)-, neurotensin-and calcitonin gene related
      peptide (CGRP)- antisera were detected by immunocytochemical methods. Co
      existence of glucagon with GLP-1, and PP with PYY were observed in some cells.
      Furthermore, immunoreactivities for members of gastrin and PP families were also
      found to co-exist in a few cells. In the muscular layer, vasoactive intestinal
      peptide (VIP)- and substance P-immunoreactive nerve fibers were also found.

PMID- 18621221
TI  - Parvalbumin-immunoreactive material in the earthworm, Lumbricus terrestris.
AB  - Parvalbumin-like material was localized using an immunoeytochcmieal method, in
      neurons of the central nervous system and in cells intermingled in the skin of
      the earthworm. Lumbricus terreslris L. Parvalbumin-immunoreactive material was
      found in the cytoplasm of perikarya and neutrites, not in the nucleoplasm. In
      contrast to vertebrates, Lumbricus musculature did not contain parvalbumin
      immunoreactive material.

PMID- 18621222
TI  - Fine structure of the chorion of Manduca sexta and Sesamia nonagrioides as
      revealed by scanning electron microscopy and freeze-fracturing.
AB  - The fine structure of Manduca sexta and Sesamia nonagrioides chorion was
      investigated by scanning electron microscopy and freeze-fracturing. In both
      species the mature chorion exhibits a complex ultrastructure on its outer
      surface, with a large number of aeropyles forming polygonal arrays. The micropyle
      is surrounded by a rosette of approximately 80 follicular cell imprints. Scanning
      electron microscopy of vertically ripped sections reveals that both chorions
      consist of two main layers: a trabecular layer closest to the oocyte and a
      lamellar layer. The technique of freeze-fracturing, utilizing single-sided and
      rotary shadowing, clearly shows that fibrils, approximately 3-4 nm in diameter,
      constitute chorionic lamellae in both species. The fibrils appear to have a
      'beaded' structure, with a 2-3 nm axial periodicity. Freeze-fracturing also
      provides a direct visualization of the helicoidal arrangement of these fibrils
      for the formation of chorion supramolecular architecture.

PMID- 18621223
TI  - An ultrastructural study of the clitellar epithelium of the earthworm Metaphire
      posthuma (vail.).
AB  - The ultrastructure of clitellar epithelium of Metuphire posthuma revealed mainly
      three types of secretory cells. Most prominent among these are the large slender
      granular cells which contain a large number of secretory granules filling in the
      entire columncr region of the cell. The secretory granules are 2-4mu in diameter
      with a limiting membrane and containing numerous tiny vesicles in a matrix of
      varying electron density. Basolateral rough endoplasmic reticulum and extensive
      Golgi cisternae were seen interspersed with the secretory granules. The Golgi
      cisternae in these cells were quite prominent extending all around the secretory
      granules. The secretory granules of type 2 cells are spheroid bodies with motley
      appearance due to varying electron density of the matrix. The immature granules
      contain fibrillar material. Type 3 cells contained electron lucent membrane-bound
      mucous like secretory granules which are reticulated with filamentous materials.
      All the three cell types open to the exterior at the cuticular region which is
      characterised by the presence of numerous microvilli.

PMID- 18621224
TI  - Peritrophic membrane structure and formation in the larva of a moth, Heliothis.
AB  - The peritrophic membrane (PM) in tobacco budworm larvae (Heliothis virescens,
      Lepidoptera: Noctuidae), is a continuous sac which encloses the food bolus in the
      midgut and hindgut. The PM is a single-walled structure 3-5 mum thick which is
      comprised of two main layers or laminae. The laminae may be fused into a single
      structure or remain separated by a space which may contain additional thin
      strands of matrix. Staining with an anti-PM antibody and wheat germ agglutinin
      (WGA) illustrate the laminar nature of the PM and suggest that protein and chitin
      have co-incident spatial distributions within the matrix. By transmission
      electron microscopy, the PM is composed of a loose network of fibrils and small
      granules, the only structural difference among laminae being a compaction of the
      matrix along the edges of the two limiting laminae facing the endoperitrophic and
      ectoperitrophic spaces. By scanning electron microscopy, the PM surface has a
      wrinkled, felt-like texture without pores or slits. Contrary to the classical
      view that lepidopterans are Type I insects with respect to PM formation in which
      the PM forms along the full length of the midgut, the PM in the tobacco budworm
      forms primarily from secretions of specialized midgut epithelial cells at the
      junction of the foregut and midgut. The secretory cells, their secretions and the
      nascent PM stain intensely with the anti-PM antibody but not with WGA suggesting
      that chitin is added more posteriorly. The PM may be supplemented by the addition
      of minor amounts of matrix material along the length of the midgut. PM synthesis
      begins during embryogenesis prior to the initiation of feeding. The PM in
      neonates is only about 0.1 mum thick but otherwise is structurally similar to
      that in older larvae.

PMID- 18621225
TI  - Secretion and stabilization of the layers of the egg capsule of the dogfish
      Scyuorhinus canicula.
AB  - The egg capsule of the dogfish is a unique, collagcnous, layered structure
      secreted by the nidamental gland which has nine, remarkably discrete, transverse
      zones of tubular glands. The present paper traces the origin of the four layers
      of the capsule to particular zones within the gland. Evidence is presented for
      the existence of DOPA, DOPA oxidase. protein(s) rich in tyrosyl residues and a
      peroxidase within the same storage granules within the secretory cells of the C
      and E zones. It is suggested that these interact when secreted to cross-link the
      inner and outer surfaces of the egg capsule. Evidence is presented that the
      middle layer which forms the bulk of the thickness of the egg capsule and has the
      highest collagen content may be partly stabilized by the peroxidation of tyrosyl
      residues. The mechanical significance of crosslinking in this system and the
      possible cytological mechanisms involved in the secretion of the tanning agents
      and enzymes are discussed.

PMID- 18621226
TI  - Invertebrate myosin filament: Parallel subfilament arrangement in the wall of
      solid filaments from the honeybee, Apis mellifica.
AB  - Transverse serial sections (100-140 nm thick) of solid myosin filaments of the
      honeybee, Apis mellifica, were photographed in a JEM-200 electron microscope at
      200 kV. The images were digitized and computer processed by rotational filtering.
      87% of the myosin filaments showed 6-fold symmetry in their power spectra,
      confirming the results of earlier works (Beinbrech et al., 1988, 1991). To
      determine if the subfilaments were arranged parallel to the filament backbone,
      two methods were used. First, the three images of each myosin filament in the
      three serial sections were superimposed. 85% of the resulting images showed a
      strong peak for 6-fold symmetry and the averaged images showed 6 pairs of
      subfilaments, which gives evidence for parallel arrangement of the subfilaments
      relative to the filament axis. This result was confirmed by the second method in
      which a 3-dimensional reconstruction was made. An average image was made from the
      images of the same 17 myosin filaments from each of the three sections. The data
      for the 3-dimensional reconstruction were collected by tracing the outlines of
      the structures in the three successive sections. The resulting stereo image shows
      a parallel arrangement of the subfilaments.

PMID- 18621227
TI  - Oosome formation in two ichneumonid wasps.
AB  - During oogenesis of two hymenopteran species. Cosmoconus meridionator and
      Lissonota catenator, the place of origin and the ways of transport of two oosome
      components have been shown. The first constituent is produced in the trophocytes
      cytoplasm as the nuagemitochondria complexes (NM complexes). The NM complexes
      subsequently are transported via intercellular bridges to the oocyte and along
      the oolemma to its posterior pole. At the same time, near the posterior pole, the
      other structures connected with the oosome formation appear. Most probably they
      are produced in the ooplasm and have the appearance of nuage of moderate density
      (NMD). The two structures are composed of proteins and do not contain RNA
      (toluidine blue test). The NM complexes as well as the NMD disappear as the
      definite oosome forms at the posterior pole of the oocyte. At the same time the
      oosome becomes RNA positive. It is suggested that the oocyte nucleus is not
      involved in the process of the oosome formation.

PMID- 18621228
TI  - Cephalic structures in the nemertine Parborlasia corrugatus-Are they really eyes?
AB  - The opinion as to whether tiny, approximately 0.1 mm large spots around the
      innermost margin of the cephalic slits in the Antarctic nemertine worm
      Parborlasia corrugatus represent photoreceptors or not has fluctuated over the
      years. This first electron microscope study of the enigmatic spots fails to
      detect any screening pigment granules, rhabdomeres, or lamellae, but reveals that
      the structure in question is principally made up of two types of cell,
      characterized by vesicular and vacuolar material of approximately 80 nm and 0.3
      mum in diameter, respectively. Filamentous connective tissue strands with gaps
      for axons surrounds the 'eye-spot' and it is suggested that either exposure to
      the bright Antarctic summer light has led to a total disintegration of all visual
      membranes or these structures do not represent eyes at all.

PMID- 18621229
TI  - Ultrastructural studies of the mantle and the periostracal lamina in the manila
      clam, Ruditapes philippinarum.
AB  - The four folds of the mantle and the periostracal lamina of R. philippinarum were
      studied using light, transmission and scanning electron microscopy to determine
      the histochemical and ultrastructural relationship existing between the mantle
      and the shell edge. The different cells lining the four folds, and in particular
      those of the periostracal groove, are described in relation to their secretions.
      The initial pellicle of the periostracum arises in the intercellular space
      between the basal cell and the first intermediate cell. In front of the third
      cell of the inner surface of the outer fold, the periostracal lamina is composed
      of two major layers; an outer electron-dense layer or periostracum and an inner
      electron-lucent fibrous layer or fibrous matrix. The role and the fate of these
      two layers differ; the outer layer will recover the external surface of the shell
      and the inner layer will contribute to shell growth.

PMID- 18621230
TI  - Induction of choriogenesis by 20-hydroxyecdysone in the German cockroach.
AB  - Experiments in vitro have shown that 20-hydroxyecdysone (at a concentration of
      0.2 and 2 microM and after 12 and 24 hr of incubation) is able to induce the
      precocious deposition of chorion materials by the follicular epithelium of young
      oocytes of the cockroach Blattella germanica. Since previous studies had shown
      that 20-hydroxyecdysone levels in B. germanica ovaries increase with oocyte
      maturation to reach a peak just before oviposition, we therefore hypothesize that
      ovarian ecdysteroids trigger Choriogenesis in this species through an autocrine
      action.

PMID- 18621231
TI  - The precocious commitment of wing Anlagen in Tenebrio molitor revealed by the
      addition of 20-hydroxyecdysone.
AB  - An injection of 20-hydroxyecdysone (10 mug per animal) 6-13 days after the moult
      of the last larval instar of Tenebrio molitor induces the development of
      prothetelic larvae and larval-pupal intermediates. The state of larval-pupal
      switchover, or commitment, is only disclosed at the time of injection of the
      moulting hormone. Prothetelic A and B larvae, with small and medium sized wing
      Anlagen, undergo another larval or pupal instar. Prothetelic C larvae with bigger
      Anlagen are unable to moult, but the adult programme is expressed. Ecdysed larval
      pupal intermediates give more or less perfect adults, while unecdysed mealworms,
      imprisoned in their larval cuticle, also expressed the adult programme. The
      commitment of Tenebrio is not a global switchover because a significant
      asynchronisation is noted between the development of organs considered. Animal
      crowding induces a delay in the appearance of wing Anlagen.

PMID- 18621232
TI  - Cellular differences in ring glands of flesh fly pupae as a consequence of
      diapause programming.
AB  - The ultrastructure of the ring gland (corpus cardiacum (CC), prothoracic gland
      (PG) and corpus allatum (CA)) was examined in diapausing and nondiapausing flesh
      fly pupae. The diapause developmental state, which is environmentally regulated
      and coordinated by the brain-ring gland complex, is associated with differences
      in the ultrastructure of PG and CA cells but not in the CC. During diapause the
      PG and CA cells have extensive arrays of rough endoplasmic reticulum and
      spherical mitochondria. The PG cells also contain lipid droplets surrounded by an
      electron dense amorphous coat not seen in PG cells from nondiapausing pupae. In
      nondiapausing pupae, the PG and CA cells contain large amounts of ribosomes
      throughout the cytoplasm but very little rough endoplasmic reticulum and
      elongated mitochondria. The fact that ring glands from diapausing pupae readily
      incorporate (35)S-methioninc indicates that the gland is actively synthesizing
      proteins, thus the contrasts in ring gland ultrastructure are not due to cellular
      quiescence during diapause but reflect fundamental cellular and physiological
      differences between the diapause and nondiapause developmental program.

PMID- 18621233
TI  - The hagfish oocyte at late stages of oogenesis: structural and metabolic events
      at the micropylar region.
AB  - The hagfishes (Class Agnatha), primitive vertebrates and massive secretors of
      mucus, occupy a unique niche in a marine benthic environment and exists in
      abundance despite an infrequent ovulation of a low number (12-45) of notably
      large, prolate ellipsoidal (approximately 8 mm x 28 mm, width x length,
      respectively) eggs. To establish factors that might contribute to survivability
      of one species (Eptatretus stouti), we examined three groups of mature females
      and document structural events characteristic of oocytes at late developmental
      stages: attached to the gonad, after ovulation into the body cavity, and after
      deposition on aquaria substrata. Quantitative autoradiographic analyses following
      administration in vivo of [(3)H]-leucine was useful to confirm post-vitellogenic
      stages and late metabolic events at the micropylar region located at one end of
      each egg. After egg disassembly, a combination of light microscopy and scanning
      electron microscopy was used to delineate structural features and 3-D
      relationships in juxtaposition to the micropylar cup and canal. A thick
      (approximately 200 microm) complex tripartite chorion surrounds a large
      micropylar cup (approximately 300 microm, width at base) consisting of fused
      polygonal (mainly hexagonal) substructural units (3-4 microm, width) and
      collectively serves to stabilize the micropylar canal (of size to prevent
      polyspermy) that penetrates the ooplasm near the germinal vesicle. A tuft
      composed of numerous chorionic appendages ('anchor filaments', approximately 2-3
      mm length) is enmeshed in a gel matrix and surrounds the cup. When the eggs are
      deposited, intermediate filament aggregates (IFA) from slime gland mucus become
      interspersed in the tuft/gel complex. A similar IFA/tuft/gel region found on the
      vegetal pole-end facilitates firm egg-end attachments and possibly assists
      localization of egg clutches to a favorable substratum. Although the mode of
      fertilization is as yet unknown, the collective structural characteristics of the
      hagfish egg arc indicative of physical strength and are markedly different from
      eggs of the other group of cyclostomes (lampreys) and from teleosts. The hagfish
      produces fewer but larger eggs which are prolate ellipsoidal rather than
      spherical and have a thicker chorion, a greater chorion to egg width ratio, a
      much larger micropylar cup with a unique substructure, larger and more localized
      chorionic appendages, and appendage tufts interspersed with adhesive substances
      derived not only from the follicular epithelium but also from the slime glands.

PMID- 18621234
TI  - Localization of putative biochemical messengers during Eisenia foetida (Annelida,
      Oligochaeta) development.
AB  - This histochemical-immunohistochemical study was performed on the earthworm
      Eisenia foetida at different developmental stages, to investigate the presence
      and distribution of cholinergic molecules (AChE, BuChE, alpha-bungarotoxin
      binding sites), several biogenic amines (5HT and catecholamines), and some
      immunologically-related peptides (somatostatin. FMRF-amide, VIP, substance-P,
      bombesin). The results showed that the pattern of labelling for the markers is
      different at different stages. In summary, cholinesterases appeared widely
      distributed in the early embryonic stages. They then were localized in particular
      areas of the developing nerve and muscle tissues, whereas in newborn and adult
      earthworms they were restricted to ventral muscular fibers and to some CNS cells.
      Biogenic amines were constantly present in the embryonic and adult nervous
      tissues. Immunologically-related peptides were detectable after organogenesis.
      Our results provide indirect evidence for a role of cholinesterases in regulating
      early intercellular communications, neurogenesis and myogenesis, and support the
      hypothesis that some conservative sequences of messenger peptides arose very
      early in evolution.

PMID- 18621235
TI  - Two kinds of thick filament in smooth muscle cells in the adductor of a clam,
      Chlamys nobilis.
AB  - The ultrastructure of the opaque portion of the adductor muscle in the pecten
      Chlamys nobilis was investigated. The opaque portion was composed of smooth
      muscle cells that contained thin and thick filaments. The thick filaments were
      classified into two kinds, thinner and thicker, according to the statistical
      analysis of diameters. They were also classified as being shorter and longer,
      when isolated native filaments were examined. The thick filaments may
      consequently be classified into two kinds: thinner and shorter filaments, and
      thicker and longer ones. The thinner and shorter filaments were about 26.5 nm in
      diameter and 7.5 mum in length, and the thicker and longer ones were about 42.0
      nm in diameter and 13.0 mum in length, respectively. A regular periodicity was
      apparent on the surface of the core after removal of myosin molecules from its
      surface. The periodicity seemed similar for the two kinds of thick filament.

PMID- 18621236
TI  - Morphological responses of dissociated sponge cells to different organic
      substrata.
AB  - To study interactions between sponge cells and components of the extracellular
      matrix (ECM), cells of the calcareous sponge Clathrina cerebrum were investigated
      in vitro by scanning electron microscopy. Cells were settled on glass coverslips,
      used as controls, and on coverslips coated with various ECM components (laminin,
      collagens and fibronectin), and with an adhesive substance (polylysine). Cells
      tended to conserve a rounded shape, producing thin, stiff processes (scleropodia)
      and lamellipodia, whose shape and extension varied according to the substrata.
      Spreading was observed only on polylysine, inducing cells to assume a fibroblast
      like aspect. On laminin, cell adhesion was assured only by scleropodia. On
      fibronectin, scleropodia and lamellipodia were present, but reduced in size and
      length. On collagens, laminar processes occurred among prevailing scleropodia.
      Measurements of cell area and perimeter allowed statistical comparison of
      substrata, on the basis of their induction of cell flattening and protuberance
      formation. In summary, sponge cells were found to modulate their morphology in
      response to the external environment, expressing features for dynamic activities
      most fully in the presence of substances close to their natural ECM constituents.
      These results are discussed in the context of tissue rearrangement as a basic
      adaptation occurring throughout the life span of these organisms.

PMID- 18621237
TI  - Ultrastructural studies on the nematode Xiphinema diversicaudatum: Egg shell
      formation.
AB  - The ultrastructure of the formation of the egg shell in the longidorid nematode
      Xiphinema diversicaudatum is described. Upon fertilization a vitelline membrane,
      which constitutes the vitelline layer of the egg shell, is formed. The chitinous
      layer is secreted in the perivitelline space, between the vitelline layer and the
      egg cell membrane. On completion of the chitinous layer, the material of the
      lipid layer is extruded from the egg cytoplasm to the outer surface, through
      finger-like projections. Both chitinous and lipid layers are secreted by granules
      in the egg cytoplasm that disappear as the layers are completed. Chitinous and
      lipid layers are formed during the passage of the egg through the oviduct. The
      vitelline layer is enriched with secretions produced by the oviduct cells and
      then by phospholipids secreted by the cells of the pars dilatata oviductus. The
      inner uterine layer is also formed by deposition of secretory products apposed on
      the egg shell in the distal uterine region and Z-differentiation. In the proximal
      part of the uterus, the egg has a discontinuous electron-dense layer, the
      external uterine layer. Tangential sections between chitinous and uterine layers
      revealed the presence of holes, possibly egg pores, delimited by the two uterine
      layers.

PMID- 18621238
TI  - Ultrastructural studies on the nematode Xiphinema diversicaudatum: Oogenesis and
      fertilization.
AB  - Oogenesis and fertilization in longidorid nematodes has been examined for the
      first time at electron microscope level in Xiphinema diversicaudatum. Oogonia in
      the germinative zone of the ovary are irregularly shaped and lie adjacent to each
      other or separated by processes of the epithelial cells of the ovary. Developing
      oocytes pass in single file up to the growth zone and fibrogranular formation
      occurs around their nucleus. The perinuclear deposits remain until the oocyte is
      fully grown. Oocytes increase rapidly in volume because of the production of
      secretory granules. Three types of granules are recognizable. Type 1 granules are
      spherical, amorphous in structure and delimited by a lighter area, probably
      consisting of lipoprotein. Type 2 granules, electron lucent, arranged in groups,
      are lipid inclusions. Type 3 are dense spheres and may represent yolk bodies. The
      two last are then utilized by the developing embryo. Mature oocytes assume a
      smooth, cylindrical configuration as they traverse the oviduct. A cone of
      fertilization seems to be formed at the distal pole of the oocyte, where the
      sperm penetrates. The sperm totally penetrates the oocyte, through an
      invagination formed at the oocyte surface. The oocyte continues to undergo two
      unequal cytoplasmic divisions, resulting in the formation of a female pronucleus
      and two polar bodies. Under the stimulus of fertilization, a new egg cell
      membrane is produced, the first one becoming the vitelline envelope.

PMID- 18621239
TI  - Properties of the esophageal epithelium in relation to organizative patterns of
      lymphoid infiltrations in the red-eared turtle.
AB  - The esophagus of the turtle, like the mucosal surfaces in other species, contains
      variously sized areas of lymphoid infiltration. The tunica propria and the
      surface epithelial layer of this area are invaded by the lymphoid cells. The
      features of the layer of epithelial cells which cover the lymphoid infiltrations
      are of a special kind: they do not possess vibratile cilia and are able to take
      up materials flowing into the lumen. The present paper contains further
      information concerning lymphoid infiltration obtained by histological and
      histochemical methods. The epithelial layer covering the lymphoid infiltrations
      is composed of cells with irregularly distributed microvilli, ciliated cells and
      mucous-secreting cells. After administration of silica and colloidal carbon, the
      microvillar epithelial cells proved to have these substances inside them, thereby
      accounting for the pinocytotic activity. The absorbing epithelial cells were not
      damaged by silica which is a macrophage-toxic agent, while the underlying
      macrophages are damaged. These results are compared with the features of lymphoid
      infiltration associated cells in various organs and animals; the hypothesis is
      proposed that these cells in the esophagus of turtles may originate from the
      covering epithelial cells.

PMID- 18621240
TI  - Dynamics of the oocyte cortical cytoskeleton during oogenesis in Rhodnius
      prolixus.
AB  - The oocyte cortex undergoes dramatic changes during oogenesis in Rhodnius
      prolixus. Despite numerous studies examining oogenesis in the telotrophic
      ovariole, none has investigated the ultrastructural details of the oocyte cortex,
      in particular, the lateral cortical cytoskeleton. Indirect immunofluorescent
      staining of sections, rhodamine phalloidin staining of whole mounts and scanning
      and transmission EM of permeabilized and unpermeabilized preparations revealed
      the dynamic changes of the oocyte cortex from early previtellogenesis through to
      late vitellogenesis. During early previtellogenesis, oocytes 50-150 mum in length
      have a smooth oolemma, with no discernible cortical cytoskeleton. During mid to
      late previtellogenesis (oocytes 150-350 mum in length) a tightly woven network of
      microfilaments and microtubules forms, excluding mitochondria and Golgi complexes
      from the lateral cortex. At the onset of vitellogenesis, the follicuiar
      epithelium becomes patent, and there is an increase in microvilli covering the
      lateral oocyte surface. The microfilament cores form a discrete pattern that
      corresponds to the imprint of the follicle cells on the oocyte surface. While the
      lateral microfilament cytoskeleton becomes more elaborate, the lateral
      microtubule cytoskeleton diminishes, remaining sparse throughout vitellogenesis.
      The oocyte cortical cytoskeleton undergoes dramatic changes during oogenesis.
      These cortical dynamics are intricately related to the cellular and molecular
      processes that occur during oogenesis.

PMID- 18621241
TI  - In vivo distribution of immune protein scolexin in bacteria-injected Manduca
      sexta larvae.
AB  - The Manduca sexta larva-specific immune protein, scolexin, was isolated and
      (14)CH(3)-labelled by reductive alkylation. The influence of the bacterium
      Streptococcus faecalis on the hemocoelic distribution of the labelled scolexin
      was then analyzed. During bacterial challenge, most of the scolexin signal was
      detected in association with the hemocyte aggregations and nodules which formed;
      in this respect the protein sometimes appeared to be associated with hemocytes
      which had phagocytized bacteria, while at other times it was most concentrated in
      the nodule-associated, and free, coagulum. Areas of high scolexin activity were
      sometimes detected at various sites on the surface of the fat body. The scolexin
      did not appear to bind directly to bacterial cells. Up to 24 hr following the
      injection of S. faecalis, the larvae were still carrying out the formation of
      nodules; unlike the nodules of the 3 and 6 hr intervals, the nodules observed at
      21-24 hr were covered with an apparently humorally derived, coagular capsule.

PMID- 18621242
TI  - Ultrastructural localization of tyrosinase in the tardigrade cuticle.
AB  - Tyrosinase activity has been demonstrated ultra-structurally in the cuticle of
      the eutardigrade Macrobiotus hufelandi. The enzyme could be localized in the
      outer layer (=epicuticle) of the integument. A weak deposition of reaction
      product was also seen in the cytoplasm of storage cells, free floating in the
      haemolymph.

PMID- 18621243
TI  - Nuclear changes during spermiogenesis in two chrysomelid beetles.
AB  - Ultrastructural and cytochemical studies were carried out on sperm nucleus of the
      beetles, Coelomera lanio and Diabrotica speciosa. Nuclear development involves
      changes in the shape and in the degree of chromatin condensation, with specific
      aggregation patterns of DNA-histone complex occurring during this process.
      Lamellar and paracrystalline arrangements of the nuclear material were observed
      in the Diabrotica speciosa spermatid and in the Coelomera lanio spermatozoon,
      respectively. Ethanolic-phosphotungstic acid technique suggest the presence of
      basic proteins in the nuclear material of spermatids. This reaction disappears
      during chromatin condensation. Chromatin condensation patterns may reflect
      specific intranuclear mechanisms and offers protection to the genome during
      spermatozoon transport to the oocyte.

PMID- 18621244
TI  - Morphogenesis of the antenna of the male silkmoth, Antheraea polyphemus. IV.
      Segmentation and branch formation.
AB  - The imaginal antenna of the male silkmoth Antheraea polyphemus is a featherlike
      structure; its flagellum consists of about 30 stem segments each giving off two
      pairs of side branches. The antenna develops during the pupal stage (lasting in
      total about 21 days) from a leaf-shaped anlage by incisions proceeding from the
      periphery towards the prospective antennal stem. Primary incisions, starting
      about 3 days after apolysis, form double branches, which arethen split into
      single branches by parallel running secondary incisions. The initial pattern of
      tracheae and peripheral nerves is completely rearranged during these
      morphogenetic processes which are finished 9-10 days after apolysis. In Antheraea
      the dorsal and ventral epithelial monolayers of the antennal anlage are
      successively subdivided during development into a pattern of repetitive
      epithelial zones. Within the first day after apolysis alternating stripes of
      sensillogenic and non-sensillogenic epithelium are differentiating. Then the
      latter are further subdivided, and at last four different stripelike zones (I-IV)
      can be discriminated. Long basal protrusions of the epidermal cells ('epidermal
      feet'), and most probably haemocytes, seem to be involved in the reconstruction
      of the epithelium: both show characteristic arrangements within the antennal
      anlage during successive developmental stages.

PMID- 18621245
TI  - The amylase-secreting cells of the stomach of the scallop, Pecten maximus:
      ultrastructural, immunohistochemical and immunocytochemical characterizations.
AB  - (1) alpha-amylase was extracted and purified from the stomach/digestive gland
      complex of the scallop Pecten maximus and an anti-serum was induced against the
      purified amylase by rabbit immunization. (2) The anti scallop amylase was used to
      localize the amylase-secreting cells in the stomach of Pecten maximus by
      immunofluorescence and immunogold labelling. The amylase-secreting cells are
      glandular cells particularly numerous in the main sorting area of the stomach.
      Their secretory granules were found strongly positive for anti-amylase. Three
      types of glandular cells were observed, actually corresponding to the three
      stages of the glandular-cell activity, synthesis, secretion and excretion. (3)
      The synthesizing cell shows the characteristic features of a protein-synthesizing
      cell: a conspicuous nucleolus and abundant granular endoplasmic reticulum. In the
      secretory cell, the secretory granules are formed by the Golgi apparatus and
      accumulate in the apical part of the cell. The secretory cell is filled with two
      types of secretory granules which are released in the stomach lumen by apocrine
      excretion. (4) The present study brings the first demonstration of the synthesis
      and extracellular release of amylase by glandular cells of the stomach epithelium
      of a bivalve.

PMID- 18621246
TI  - Neuropeptides and monoamines in the carp (Cyprinus carpio) pretectum: An
      immunocytochemical study.
AB  - The distribution of neurotensin, neurokinin A, dynorphin A, galanin, somatostatin
      28 (1-12), neuropeptide Y, vasoactive intestinal polypeptide, gastrin-releasing
      peptide, gamma-melanocyte stimulating hormone, alpha-neo-endorphin, angiotensin
      H, cholecystokinin-8, serotonin and tyrosine hydroxylase has been studied in the
      pretectal nuclei of the Cyprinus carpio: nuclei pretectalis superficialis
      parvicellularis and magnocellularis, pretectalis centralis, pretectalis, and
      pretectalis periventricularis dorsalis and ventralis using an indirect
      immunoperoxidase technique. We have found neuropeptide Y and serotonin
      immunoreactive fibres in all pretectal nuclei, whereas gastrin-releasing peptide
      immunoreactive fibres were visualized in the nuclei pretectalis superficialis
      parvicellularis and magnocellularis, pretectalis centralis. pretectalis and
      pretectalis periventricularis dorsalis; neurokinin A immunoreactive fibres in the
      nuclei pretectalis superficialis parvicellularis and magnocellularis and
      pretectalis periventricularis dorsalis; galanin immunoreactive fibres in the
      nuclei pretectalis superficialis parvicellularis, pretectalis centralis and
      pretectalis periventricularis dorsalis; and neurotensin immunoreactive fibres in
      the nucleus pretectalis periventricularis dorsalis. Additionally, immunoreactive
      cell bodies containing neuropeptide Y were observed in the nuclei pretectalis
      superficialis parvicellularis and pretectalis periventricularis dorsalis, and
      serotonin and tyrosine hydroxylase cell bodies were found in the nuclei
      pretectalis periventricularis dorsalis and ventralis respectively. The presence
      of the neuroactive substances found in the carp pretectal nuclei suggest that
      they might be involved in the regulation of certain functions within the visual
      system.

PMID- 18621247
TI  - NPY- and C-PON-immunoreactive substances in the central nervous system of Helix
      pomatia.
AB  - The distribution of neuropeptide-tyrosin (NPY)- and C-flanking peptide of
      neuropeptide-tyrosine (C-PON)-immunoreactivities in the central nervous system of
      the pulmonate gastropod, Helix pomatia, was investigated. NPY- and C-PON-like
      substances were localized in neuronal somata and neuntes, but were not co
      localized within the same cells. NPY-immunoreactive substances were also found in
      endocrine/paracrine like cells located in the epineurium. C-PON and NPY, both
      reduced serotonin activated isometric contractions of Helix aorta, suggesting
      that they may act as modulators in the control of the vascular system.

PMID- 18621248
TI  - Dynamics of 'immotile' olfactory cilia in the silkmoth Antheraea.
AB  - Living olfactory sensory dendrites of the silkmoth Antheraea which are modified
      cilia lacking the central microtubule pair have been observed by means of video
      microscopy in sensilla from which the apical tips had been pinched off as well as
      in vitro after isolation. Dendrites project out of the opened hair tips cither
      spontaneously without manipulation or after application of basal pressure via a
      syringe connected to the haemolymph side. Spontaneously appearing dendrites can
      repeatedly project up to ca. 60 mum from, and retract back into, the hairs. They
      tend to remain straight, but curve if they project too far and bend on meeting an
      obstacle. The average elongation velocity of the dendrites is 0.4 mum/sec. After
      application of basal pressure, large numbers of dendrites immediately slide out
      of the apically opened hairs. These dendrites usually detach at their bases and
      float free in the solution until settling down at the bottom of the petri dish.
      They are able to make active movements, for example bending between points of
      attachment. Dendrites tend to adhere to other dendrites, sometimes making sliding
      movements against each other. The ciliary olfactory dendrites are backed by a
      large number of microtubules which appear to be interconnected by fine filaments,
      most probably microtubule-associated proteins (MAPs). The elongation and
      shortening of the dendrites is explained here by a sliding-filament mechanism
      similar to the one acting in 'true motile' cilia. As the cytoskcleton is not as
      highly organized as in the latter, the resulting movements are limited to
      elongation and contraction, bending being brought about only passively by apical
      resistance. Membrane beads have been observed to appear on, and move along, the
      dendrites. Their number increases with the age of the preparation.

PMID- 18621249
TI  - The fine structure of the eggshell of the laid egg of Locusta migratoria
      migratorioides.
AB  - Ultrastructural analysis disclosed a regional diversification of the eggshell of
      the Locusta migratoria m. (L.m.m.) egg. This diversification is discussed taking
      into account the data about water permeability of the L.m.m. egg. The presence of
      several kinds of openings in the exochorion implies that in addition to the
      micropyles, the L.m.m. egg is provided with a respiratory system, especially in
      its anterior pole. The respiratory system of insect eggs is briefly reviewed. The
      presence of a wax layer in the L.m.m. egg is also discussed.

PMID- 18621250
TI  - A fine structural analysis of serosal cuticulogenesis in the egg of Locusta
      migratoria migratorioides.
AB  - The typical outer coat (the yellow cuticle) disclosed in the Locusta migratoria
      migratorioldes egg appears to be a usual formation in Acrididae; its
      physiological significance is discussed. There is a diversification of the
      epicuticle in the anterior egg pole, very likely related to a diversified water
      permeability of the egg. Three main regions of the endocuticle show that the
      cuticulogenesis proceeds in three main phases, each region being characterized by
      its own texture. The change in texture appears to be related to changes in water
      loading by the developing egg. Elucidation of the factors controlling the texture
      of the serosal cuticle was attempted. The assumption, that change in texture may
      reflect a phase behaviour reminiscent of that of a lyotropic liquid crystal
      polymer in aqueous solution, is discussed.

PMID- 18621251
TI  - The osmoregulatory tissue around the afferent blood vessels of the coxal gills in
      the estuarine amphipods, Grandidierella japonica and Melita setiflagella.
AB  - By electron microscopy of the coxal gills in two species of estuarine amphipod
      crustaceans, Grandidierella japonica and Melita satifragella, we found a patch
      like, specialized tissue area which consisted of unique cells closely resembling
      the salt-excreting cells in the gill of the brine shrimp and so-called chloride
      cells in teleost gills. These cells were characterized by an abundance of
      mitochondria, two kinds of extensive networks of cytoplasmic tubules, well
      developed lamellar infoldings of the basal cell membrane, sparse microvillous
      projections of the apical border, and numerous large vacuoles with several
      incomplete partitions. The large (60 nm in diameter) and the small (30 nm)
      cytoplasmic tubular networks were found in the basal and the apical portions of
      the cell, respectively. The large networks, which were both directly and
      indirectly (through the lamellar system) continuous with the basal cell membrane,
      were regarded as extensions of the cell membrane. Both the outer walls and the
      partition walls of the vacuoles were reinforced with a parallel array of
      microtubules. The results suggest that this unique tissue plays an important role
      in the active transport of electrolytes to maintain a constant osmotic pressure
      of the hemolymph under widely fluctuating salinities of the estuarine
      environments.

PMID- 18621252
TI  - An immunocytochemical and ultrastructural study of a specialized glial region of
      the medulla oblongata of the adult and juvenile grey mullet.
AB  - Electron microscopy together with glial fibrillary acidic protein (GFAP) and
      vimentin immunocytochemistry reveals the presence of a specialized glial region
      in the octavolateral area of the medulla oblongata of adult and juvenile grey
      mullets, Chelon labrosus. Glial cells, which can he characterized as ependymal
      and subependymal cells, originate in the walls of the lateral recess of the
      fourth ventricle. They contain numerous gliofilaments and are connected through
      frequent gap junctions. Electron microscopy also reveals the lack of nerve cell
      parikarya and processes in this region. Immunocytochemistry reveals that the
      glial cells are strongly GFAP-positive in both adults and juveniles, whereas
      vimentin is only detected in this region in juveniles. The meninges associated
      with this glial region contains connective fibres, formed of very thick collagen
      fibres, that arc metachromatic and PAS-positive under light microscopy. These
      findings strongly support a structural role for this medullary specialization.
      Differences between adults and juveniles in the distribution of GFAP- and
      vimentin-immunoreactive structures in other regions of the medulla oblongata are
      also reported.

PMID- 18621253
TI  - The persistence of Golgi complexes during cell division in an insect epidermis.
AB  - The Golgi complexes of animal cells are said to become vesicular during cell
      division in order to allow the equal partitioning of organelles between daughter
      cells (Warren, 1985). However, in the epidermis of fifth stage larval Calpodes
      ethlius (Lepidoptera, Hesperi idae), cutical deposition is concurrent with cell
      division in preparation for pupation. We therefore looked at the Golgi complexes
      of these epidermal cells to see if they maintained their interphase form to allow
      them to continue to function during cell division. Dividing cells were recognized
      by changes in the nucleus and nuclear envelope, the form of the cell cortex and
      cell surface, and by the disposition of microtubules. Epidermal Golgi complexes
      consist of 3-5 cisternae capped by endoplasmic reticulum with transfer vesicles
      and rings of GC beads next to the cis face, and secretory vesicles on the trans
      face. Golgi complexes of dividing cells are structurally indistinguishable from
      those in interphase, their beads are in the rings characteristic of active GCs,
      and cuticle continues in uninterrupted lamellae above the apical microvilli. The
      observations suggest that Golgi complexes in dividing insect cells differ from
      those of most vertebrates by remaining functional through mitosis.

PMID- 18621255
TI  - Ultrastructure of spermatogonia, spermatocytes, and sertoli cells in the testis
      of the crayfish, Procambarus paeninsulanus.
AB  - The testes of the crayfish, Procambarus paeninsulanus, were prepared for light
      and transmission electron microscopy. During early stages of spermatogenesis,
      when the spermatogonia are dividing, processes from a single Sertoli cell extend
      between numerous spermatogonia. As the cells enter meiosis, many points of
      contact can be observed between the Sertoli cell processes and spermatocytes.
      These desmosome-gap junctions are maintained between the germ and Sertoli cells
      until the early spermatid stage.

PMID- 18621254
TI  - Sperm morphology and distribution of intramembranous particles in the sperm heads
      of selected freshwater teleosts.
AB  - The morphology of spermatozoa and the distribution of intramembranous particles
      (IMPs) in sperm-head membranes in teleostean fish were examined ultrastructurally
      to clarify the presence of characteristic arrays (parallelogram or hexagon in
      packing) of IMPs. The following four species of fish were used: goldfish
      (Carassius auratus), loach (Misgurnus anguillicaudatus), flat bitterling
      (Acheilognatus rhombeus), sweetfish (Plecoglossus altivelis). It was demonstrated
      that spermatozoa of all these fish were devoid of an acrosomal structure in the
      anterior portion of the head. Spermatozoa had round heads in goldfish, loach and
      flat bitterling. Two centrioles (proximal centriole and basal body) were present
      and located adjacent to each other in all fish. The characteristic arrays of IMPs
      were found in spermatozoa of goldfish and flat bitterling. IMPs were more
      numerous on the P-face than on the E-face in all species. The present work showed
      that the characteristic arrays of IMPs were not common structures in spermatozoa
      of teleostean fish.

PMID- 18621256
TI  - The role of sertoli cells in spermatid maturation in the testis of the crayfish,
      Procambarus paeninsulanus.
AB  - With the onset of spermiogenesis, many changes become apparent in the crayfish
      spermatid during its transition to mature sperm. The nucleus passes through a
      series of stages, excess cytoplasm is removed, the acrosome develops, and nuclear
      arms form and become wrapped around the sperm prior to its enclosure in a
      capsule. Changes are also apparent in the Sertoli cells surrounding the germ
      cells in the crayfish testis. The amount of cytoplasm of individual Sertoli cells
      appears to increase in quantity and changes in the intracellular organelles
      become apparent. As spermiogenesis commences, the cytoplasm along one side of
      Sertoli cells adjacent to the spermatids is devoid of obvious organelles.
      Numerous finger/like projections of Sertoli cytoplasm penetrate into the
      spermatid and appear to isolate portions of the sperm cytoplasm. During later
      stages of spermiogenesis, several vesicles in the Sertoli cells which appear to
      contain droplets of this isolated sperm cytoplasm. appear to undergo lytic
      changes, As the amount of cytoplasm of the spermatid is reduced, contact is
      maintained between the spermatid and Sertoli cell in the area of the acrosome.
      The nuclear arms of the sperm extend into the Sertoli cell during their formation
      and later become wrapped around the acrosomal area of the sperm. At this time,
      very little space exists between the Sertoli cell and its many sperm. Large
      vesicles of electron dense material appear to be released by the Sertoli cells
      into the space between the sperm and Sertoli cell. This material completely
      surrounds the sperm and forms the sperm capsule. Spermiation involves the gradual
      dissolution of the points of contact between the sperm capsule and the Sertoli
      cell.

PMID- 18621257
TI  - Ultrastructure and maturation of a sex pheromone gland in the female German
      cockroach, Blattella germanica.
AB  - A volatile sex pheromone is produced in an adult female-specific gland located on
      the anterior of the last abdominal tergite of the female German cockroach,
      Blattella germanica (L.). In this area, the cuticle forms deep depressions in
      which a large number of cuticular orifices are located. The cuticular orifices
      are connected to secretory cells via cuticular ducts surrounded by duct cells.
      The pheromone gland exhibits a clear developmental maturation in relation to
      sexual maturation of the female. The secretory cells of a newly formed gland in
      the imaginal female are small and contain few secretory vesicles. The amount of
      extractable pheromone in the gland is low on day-0 but it increases with age and
      peaks on day-6. The secretory cells in a mature day-6 gland are characterized by
      a large number of electron-lucid secretory vesicles. abundant RER and SER, a
      large nucleus and a long, convoluted end apparatus which is lined with numerous
      microvilli. The contents of the secretory vesicles are exocytosed into
      extracellular reservoirs at the base of microvilli and then transported to the
      cuticular surface through the long ducts. The supportive function of the duct
      cell in the glandular organization and developmental regulation of the gland are
      discussed.

PMID- 18621258
TI  - Ultrastructure of growing oocytes and accessory cells in Austrognathia
      (Gnathostomulida, bursovaginoidea).
AB  - The ovary of Austrognathia cf. riedli consists of 4-6 oocytes which are located
      in the mid-body region between the epidermis and the gut epithelium. The ovary is
      not enveloped by a tunica and each growing oocyte is surrounded by one or more
      accessory cells, the function of which is hypothesized in this study. Oogenesis
      is not synchronous and can be subdivided into a previtellogenic phase and a
      vitellogenic phase. Previtellogenic oocytes undergo a number of cell
      differentiations which consist mainly of an increase in size of the nucleus and
      nucleolus and the appearance in the cytoplasm of chromatoid bodies, annulate
      lamellac and short cisternae of rough endoplasmic reticulum (RER). Vitellogenic
      oocytes are characterized by the increase of RER, the appearance of numerous
      Golgi complexes and the accumulation of electron-dense globules, glycogen and
      lipid droplets. The electron-dense globules have been interpreted as yolk on the
      basis of both their localization and composition. Yolk synthesis occurs mainly by
      an endogenous mechanism and, to a lesser extent, by micropinocytosis. No shell
      granules have been identified in the oocytes. The present ultrastructural
      findings are discussed in comparison with those from other lower metazoans.

PMID- 18621259
TI  - The effect of azadirachtin on the midgut histology of the locusts, Schistocerca
      gregaria and Locusta migratoria.
AB  - The effects of azadirachtin on midgut cells of adult Schistocerca gregaria and
      Locusta migratoria were investigated by both light and electron microscopy.
      Pathological effects were seen in both species which could be related to dose and
      time after treatment. The midgut cells showed a slow necrosis, a rounding up of
      the cell and swelling of organelles; the nidi were reduced in size and number,
      the connective tissue beneath the epidermal layer became enlarged with many
      invading cells/nuclei and the circular and longitudinal muscles become rounded
      and swollen. The pathological effects were closely linked to a loss of feeding,
      with injections of 5, 10 and 15 microg/g azadirachtin causing an increasingly
      rapid onset of the effects associated with an increasingly reduced food intake.
      At the highest dose, full histopathological effects were seen at 8 hr and death
      occurred after 3 days. At 1 microg/g, however, the insects showed midgut
      disruption and reduced feeding by day 3 post-treatment but both feeding and gut
      pathology had recovered by day 7. At all times, histopathological effects were
      different from those in starved insects.

PMID- 18621260
TI  - Neurite regeneration of long-term cultured adult insect neurosecretory cells
      identified as DUM neurons.
AB  - A distinctive group of neurons having cell bodies located along the midline of
      the dorsal surface of the sixth abdominal (A6) ganglion of the adult cockroach
      Periplaneta americana has been characterized by direct anterogradc cobalt
      chloride staining. These neurons identified as dorsal unpaired median (DUM)
      neurons, present a T-shaped morphology. The soma gives rise to a single primary
      neurite running anteriorly in the ganglion before dividing into two lateral
      neurites which run into the left and the right side of the ganglion. A
      characteristic dendritic arborization arises from the lateral neurites within the
      ganglion. This major branching pattern is mainly located at the periphery of the
      A6 ganglion and forms a symmetrical complicated network. A new culture procedure
      of these same adult DUM neurons has been developed from the dissociation of the
      median parts of the A6 ganglia. In our experimental conditions, we show that
      cultured adult DUM neurons can survive for several weeks, and regenerate a single
      primary neurite dividing into two symmetrical lateral neurites with a number of
      fine processes radiating from the endings. This corresponds to the typical DUM
      neuron morphology revealed in situ on the same preparation using the cobalt
      chloride staining technique. This culture system developed for the first time on
      A6 ganglia adult DUM neurons will allow a better understanding of the
      physiological intracellular mechanisms involved in the neurosecretory functions
      of DUM neurons, which are currently unknown.

PMID- 18621261
TI  - Characteristics of the sperm tail of the velvet worm, Euperipatoides leuckarti
      (Onychophora).
AB  - The onychophoran sperm tail contains several kinds of microtubulcs; probably more
      than that of any other animal group. There are thus a peripheral manchette
      consisting of many tightly spaced microtubules, a ring of nine 'peripheral
      singlets' and a central axoneme of the classical 9 + 2 type (nine doublets and
      two central singlets). The protofilament organization of these various
      microtubules was examined and compared to the structure and mode of formation of
      the peripheral singlets with that of its analogues in other animal groups. The
      onychophoran peripheral singlets were found to differ in two respects from those
      in insects: they are formed from the manchette rather than from the axonemal
      doublets and their transient connection to the axoneme is to the A-subtubules of
      the doublet rather than to the B-subtubules. The manchette microtubules as well
      as the peripheral singlets consist of 13 protofilaments. The manchette may serve
      a mechanical function (to strengthen the unusually thick sperm tail) hut the role
      of the peripheral singlets remains unknown.

PMID- 18621262
TI  - The ultrastructure of the sternal gills forming a striking contrast with the
      coxal gills in a fresh-water amphipod (Crustacea).
AB  - Sternomoera yezoensis has specialized sterna with 21 sternal gills in addition to
      six pairs of coxal gills. Despite a common high permeability to chloride ions,
      the epithelia of these two kinds of gills are diametrically opposed in the
      polarity of the cell membrane-mitochondria complex. The coxal gill epithelium (4
      6 microm thick) is characterized by a well-developed AIS (apical infolding
      system) associated with a huge number of large mitochondria. The AIS exceeds two
      thirds of the epithelial thickness and forms a highly sophisticated, subcuticular
      labyrinth. On the contrary, the sternal gill epithelium, an extension of the
      sternal epithelium proper, is extremely thick (10-15 microm) and is characterized
      by a very deep BIS (basolateral infolding system) associated with numerous
      slender mitochondria. The BIS reaches nine-tenths of the epithelial thickness and
      forms a giant, baso-lateral labyrinth. Shallower, less elaborate AIS and BIS
      without mitochondrial association originate from the opposite sides of these
      epithelia. Although AIS and BIS interpenetrate in the sternal gill epithelium,
      they never communicate. The results indicate that in addition to the coxal gills,
      the sterna with the sternal gills function as transporting as well as respiratory
      organs, though the functional difference between these two kinds of gills remains
      to be elucidated.

PMID- 18621263
TI  - Substructures in the core of thick filaments: arrangement and number in relation
      to the paramyosin content of insect flight muscles.
AB  - Transverse sections (100-140 nm thick) of solid myosin filaments of the flight
      muscles of the honeybee, Apis mellifica, the fleshfly, Phormia terrae-novae and
      the waterbug, Lethocerus uhleri, were photographed in a JEM-200 electron
      microscope at 200 kV. The images were digitized and computer processed by
      rotational filtering. The power spectra of the images of each of these filaments
      showed six-fold symmetry for the outer wall region and three-fold symmetry for
      the inner wall region. Images of the honeybee additionally showed three-fold
      symmetry for the center of the filament. Considering both paramyosin content of
      the myosin filaments and the results of the rotational filtering, we suggest the
      existence of 3 paramyosin strands in the myosin filaments of the fleshfly, 6
      paramyosin strands in the honeybee filaments and 5 strands in the myosin
      filaments of the waterbug. In the case of the honeybee, the 3 paramyosin strands
      of the inner wall are positioned directly opposite the myosin subfilaments, while
      the 3 strands of the center seem to be arranged opposite the gaps between the
      myosin subfilaments. The paramyosin filaments of the fleshfly wobble between 2
      myosin subfilaments, without loosing their three-fold symmetry arrangement in the
      inner wall. The 3 paramyosin strands in the inner wall of the waterbug myosin
      filaments are either arranged opposite the myosin subfilaments or opposite the
      gaps between the subfilaments. Finally, we were able to generate a 3-dimensional
      reconstruction of the myosin filament of the honeybee, showing the parallel
      arrangement of both, myosin subfilaments and paramyosin strands, relative to the
      long filament axis.

PMID- 18621264
TI  - A freeze-fracture study of mesophyll cell membranes in the embryonic Phaseolus
      leaf, in the dry seed and during the initial stages of germination.
AB  - Using rapid-freezing and freeze-fracturing techniques, we have examined cellular
      organisation within mesophyll cells in primary leaves of Phaseolus, in the dry
      seed and over a period of 48 hr from the onset of germination. The rapidly
      frozen, unetched image reveals a dynamic cytoplasm with membrane shape and role
      able to change and fluctuate with the increase in cell metabolism. The ER in this
      tissue is highly mobile, becoming progressively associated with protein and lipid
      bodies, then plastids, mitochondria and nuclei as cytoplasmic requirements
      change. The ER thus provides an efficient transport of substrates to metabolic
      sites within the cytoplasm. Nuclei and plastics change shape in early germination
      and the protein body membrane changes in role and character to that of a vacuolar
      tonoplast. The freeze-fractured image emphasizes the considerable movement that
      occurs within the cytoplasm during germination, with flexible and mobile
      membranes of the various organelles able to associate and interact with others.
      We have also measured the density of intramembrane particles on most of the
      membranes within the mesophyll parenchyma cell, during this period of early
      germination. Using our method of rapid-freezing, we find consistently higher IMP
      density on the protoplasmic face of each membrane. The counts provide a set of
      comparative values for membranes of a specific tissue, and for a specific
      cryofixation technique.

PMID- 18621265
TI  - Junctional types in the tissues of an onychophoran: the apparent lack of gap and
      tight junctions in Peripatus.
AB  - The Onychophora are a rare group of primitive invertebrates, relatively little
      investigated. Tissues from a range of their digestive, secretory and excretory
      organs have been examined to establish the features of their intercellular
      junctions. Glutaraldehyde-fixed cells from the midgut and rectum, as well as the
      renal organ, mucous gland, salivary gland, epidermis, CNS and testis from
      specimens of Peripatus acacioi, have been studied by thin section and freeze
      fracture electron microscopy. Adjacent cells in the epithelia of all these
      tissues are joined by apical zonulae adhaerentes, associated with a thick band of
      cytoskeletal fibrils. These are followed by regular intercellular junctional
      clefts, which, in thin sections, have the dense, relatively unstriated,
      appearance of smooth septate junctions (SSJ). However, freeze-fracture reveals
      that only the midgut has what appear to be characteristic SSJs with parallel
      alignments of closely-packed rows of intramembranous particles (IMPs); these IMPs
      are much lower in profile than is common in such junctions elsewhere. The mucous
      gland, testis, rectal and renal tissues exhibit, after freeze-fracture, the
      characteristic features of pleated septate junctions (PSJ) with undulating rows
      of aligned but separated junctional particles. Suggestions of tricellular septate
      junctions are found in replicas at the interfaces between 3 cells. In addition,
      renal tissues exhibit scalariform junctions in the basal regions of their cells.
      Between these basal scalariform and apical septate junctions, other junctions
      with reduced intercellular clefts are observed in these renal tissues as well as
      the rectum, but these appear not to be gap junctions. Such have not been
      unequivocally observed in any of the tissues studied from this primitive
      organism; the same is true of tight junctions.

PMID- 18621266
TI  - Interaction of collagen with hydrophobic protein granules in the egg capsule of
      the dogfish scyliorhinus canicula.
AB  - The egg capsule of the dogfish is a composite material containing collagenous
      fibrils and 2 mum spherical hydrophobic protein granules. The latter appear to
      owe much of their hydrophobicity to an exceptionally high tyrosine content
      (approximately 20% of total amino acid residues). The hydrophobic component
      appears to form as an emulsion in the secretory granules of the D and E zone
      gland cells of the nidamental gland. Droplets of the hydrophobic material appear
      to become coated with remarkably regular layers of radially-arranged collagen
      molecules which form a series of concentric, evenly spaced layers around each
      hydrophobic granule. Numerous disclinations were seen where the layers around
      adjacent granules interfered with one another. The layers are thought to
      represent a lamellar liquid crystalline phase previously described for this
      collagen (Knight et al., 1993). The fine structural appearance of the concentric
      layers and evidence for radial arrangement of collagen molecules within them is
      compatible with the suggestion that the layers are built from a dumbbell-shaped
      unit approximately 35 nm long with hydrophobic groups concentrated at the ends.
      This unit may represent a dumbbell-shaped molecule or an oligomer of two or more
      molecules lying parallel with one another in a head-to-tail arrangement. Such a
      unit can be readily incorporated into models for the micellar, hexagonal columnar
      and final fibrillar phases previously described for this collagen (Knight et al.,
      1993). Evidence from the TEM study of stretched egg capsule wall suggests that
      there is a mechanical interaction between the hydrophobic granules and the
      collagen fibrils in the fully formed material. We suggest that the radial,
      concentric layered arrangement of collagen molecules is established by
      hydrophobic interactions within the liquid crystalline material and locked into
      place by oxidative covalent cross-linking to give a 3-dimensional cross-linked
      meshwork of collagen fibrils and hydrophobic granules. The latter arrangement
      helps to account for the high tensilestrength and toughness of this material.

PMID- 18621267
TI  - Light and electron microscopical study of two types of endocrines cell in the
      midgut of the adult worker honeybee (apis mellifera).
AB  - The occurrence, development and ultrastructure of two types of gut endocrine cell
      have been studied in the midgut of adult honeybees. These cells, one of a basal
      granular type and one of a vesicular type, are evenly distributed throughout the
      posterior three-quarters of the midgut. Each crypt complex contains one of each
      cell type, both of which may be derived from the same stem cells as the
      enterocytes. They already contain their respective secretory product while still
      in the nidus. Both reach the midgut lumen by a narrow apex and are therefore of
      the open type. The granular cells release their secretory granules at the cell
      base in a typical endocrine way. In young vesicular cells the secretory vesicles
      are released at the cell base and in the intercellular spaces. Old cells are
      still filled with vesicles when they are shed in the midgut lumen. This seems to
      indicate that these cells have both an endocrine (or paracrine) and an exocrine
      function, the latter apparently by holocrinc release.

PMID- 18621268
TI  - Organisation and ultrastructure of the regenerative crypts in the midgut of the
      adult worker honeybee (L. Apis mellifera).
AB  - The midgut epithelium of the adult honeybee consists of columnar and endocrine
      cells, both originating from regenerative crypt cells. The regenerative crypt is
      composed of stem cells and differentiating cells. The stem cells generate two
      forms of endocrine cells along with differentiating enterocytes of two distinct
      stages. At first they can be seen as light crypt cells which are not secretory
      active; they then develop into more electron dense, active secretory crypt cells.
      The developing enterocytes are arranged as tetrads, each composed of cells with
      the same degree of differentiation. This can be explained by the occurrence of
      cytoplasmic bridges between the cells of each tetrad. These fusomes are probably
      responsible for the apparent intercellular coordination. This is a new example of
      intercellular bridges between somatic cells and, as far as we know the first
      description of fusomes in the insect midgut epithelium. The microvilli on top of
      the crypt cells develop within a spherical extracellular space where
      glycosaminoglycans are secreted. This occurs by the coordinated activity of the
      four surrounding electron dense crypt cells. Microvilli formation therefore seems
      to be the first in a series of successive functions of honeybee enterocytes
      during their ontogeny.

PMID- 18621269
TI  - Morphology and ontogeny of single-walled multiporous sensilla of hemimetabolous
      insects.
AB  - Comparative morphological investigations were made to determine the common
      organization plan of single-walled multiporous sensilla. The development of
      multiporous chemoreceptive sensilla of Gryllus, Oncopeltus and Lepisma follows
      the same path. Each chemoreceptive sensillum is associated with four types of
      enveloping cell. During ontogeny, enveloping cell 1 secretes the dendritic
      sheath. Enveloping cell 4 builds the connection of the hair base with the
      antennal cuticle. In Gryllus and Oncopehus, enveloping cells 2 and 3 build the
      hair shaft, the wall pores and pore tubules in nearly equal parts. Enveloping
      cells 2 and 3 lie side by side in the hair process, in which enveloping cell 2
      produces the inner part, enveloping cell 3 the outer part of the hair shaft. In
      Lepisma the predominant part of the hair shaft with the wall pores is formed by
      the doubled enveloping cells 3. Interpreting our findings and the literature
      data, a new proposal is given for the homology of the enveloping cells. In
      singlewalled chemoreceptors, enveloping cell 1 is considered as thecogen and
      enveloping cell 4 as tormogen cell. Enveloping cell 2 is interpreted as inner
      trichogcn cell and enveloping cell 3 as outer trichogen cell.

PMID- 18621270
TI  - Structure of the subgenual organ in the green lacewing, Chrysoperla carnea.
AB  - REM and TEM studies of the subgenual organ in Chrysoperla carnea (Neuroptera:
      Chrysopidae) show that it is composed of three scolopidia, each with one sensory,
      one scolopale and one cap cell. The distal part of the dendrite shows a cilium
      with a '9 + 0' structure. The cross-handing pattern of the ciliary root has a
      periodicity of bands of about 61 nm. The scolopale material in a certain part of
      the scolopale cell is organized into five rods. The cell bodies of all three cap
      cells form a lens-like structure. the velum, which is fixed to the leg wall and
      the trachea with an extracellular material. The importance of the velum is
      discussed. Four types of intercellular junction are found; spot desmosomes. belt
      desmosomes, septate junctions and gap junctions.

PMID- 18621271
TI  - Oosorption and oocyte loss in a terrestrial isopod under stressful conditions.
AB  - An increased number of resorbed oocytes was observed in ovaries of terrestrial
      isopods which were kept under different experimental temperature and photophase
      regimes compared with those observed in the natural population. Regardless of the
      nature of the stimulus: high or low temperature or long and short photophases,
      the female always responded through oosorption. In an iteroparous species such as
      Porcellio ficulneus B.-L., recruitment of resources for future utilization could
      be its main response to adverse ambient conditions.

PMID- 18621272
TI  - Some observations on the collagen fibrils of the egg capsule of the dogfish,
      Scyliorhinus canicula.
AB  - The egg capsule of the dogfish Scyliorhinus canicula is a collagenous material
      with a laminated, plywood (orthogonal) construction. The collagen fibrils which
      constitute the bulk of the egg capsule wall have a unique, highly ordered
      structure (Knight and Hunt, 1974; 1976, 1986; Gathercole et al., 1993) which is
      thought to represent a smectic A liquid crystalline phase (Knight et al., 1993).
      The egg capsule is extremely strong and chemically inert (Hunt, 1985). It is
      stored, secreted and formed by the nidamental gland (Rusaouen 1976, 1990 a, b;
      Knight and Feng, 1992). During intracellular storage, secretion and
      fibrillogenesis, the dogfish egg capsule collagen appears to pass through a
      remarkable series of textures within a lyotropic liquid crystalline phase diagram
      (Knight et al., 1993). In the present communication, further observations on the
      ultrastructure of the collagen fibrils and their arrangement within the laminae
      of the fully-formed egg capsule are reported. The effect of tilting ultrathin
      sections of fibrils in the goniometer stage of a transmission electron microscope
      are described, demonstrating that the crystalline lattice within the fibril
      appeared twisted more or less regularly into a long pitch helix. Other
      observations indicated that some of the fibrils were in turn twisted round one
      another to form fibres which therefore had a coiled-coil structure. The fibres
      are arranged parallel to one another in the laminae which are stacked to give an
      orthogonal plywood construction. The effects of staining fibrils with cuprolinic
      blue and with tannic acid are reported. Reduction in the water content of the
      fibrils before fixation appeared to move some of the fibrils through the part of
      the lyotropic phase transition diagram converting them from smectic A to smectic
      C. Finally, evidence is presented that the fibrils shrank, but remarkably, still
      retained a longitudinally-ordered but modified, molecular arrangement even after
      boiling in water for periods of up to 10 min. These observations are discussed in
      relation to other collagens.

PMID- 18621273
TI  - An unusual membrane system in the oocyte of the ascidian Botryllus schlosseri.
AB  - During vitellogenesis, oocytes of Botryllus schlosseri always exhibit an unusual
      system scattered in the cytoplasm. It consists of an association between a single
      fenestrated endoplasmic reticulum cisterna and one or a few smooth vesicles
      (cisterna vesicle association: CVA) containing a dense core facing the cisterna
      itself. The latter is smooth and perforated by numerous small pores (about 25 nm
      in diameter) in the area of association; towards the periphery, it extends into
      several branches with ribosomes bound to their membranes. In the vesicles,
      fibrillar material radiates from the dense core and is sometimes organized into a
      long, dense lamina. The membranes of both cisterna and vesicles appear to be
      coupled, but are in fact separated by a constant narrow space occupied by short
      densities. The presence in B. schlosseri of this unusual fenestrated membrane
      system contrasts with the absence of a typical porous cytoplasmic organelle, the
      annulate lamellae (ALs), which is widely distributed in female gametes. However,
      as in other animals, B. schlosseri oocytes possess intranuclear annulate lamellae
      (IALs) and vesicles. Comparative observations extended to the oocytes of the
      ascidian Ciona intestinalis have shown that the latter species exhibits typical
      ALs and IALs, but not the CVA. The morphology of the CVA is analysed here in
      detail, and similarities and differences with ALs are pointed out. Hypotheses
      regarding CVA function are discussed in terms of possible relations with ALs.

PMID- 18621274
TI  - Structure and formation of the peritrophic membrane in the larva of the southern
      corn rootworm, Diabrotica undecimpunctata.
AB  - The peritrophic membrane (PM) in larvae of the southern corn rootworm Diabrotica
      undecimpunctata (Coleoptera:Chrysomelidae) forms along the full length of the
      midgut epithelium, defining D. undecimpunctata as a Type I insect with respect to
      PM formation. PM formation occurs in three phases: organization of a continuous
      lamella of matrix from material secreted into the interstices between the
      microvilli, maturation and apical movement of the lamella along the microvilli,
      and shedding of the lamella from the tips of the microvilli into the midgut
      lumen. Subsequent cycles of synthesis and shedding give rise to multiple,
      concentric lamellae which surround the food in the gut lumen. PM lamellae are 0.2
      mum in profile width and consist of a core of bundles of 5 nm-diameter
      microfibers encased in a finely-granular homogeneous material. The microfiber
      bundles are arranged in an orthogonal grid-like array with dimensions consistent
      with formation around the microvilli. The homogeneous material separates from the
      PM lamellae to enclose food particles suggesting it may contain digestive
      enzymes. The PM, microvilli and intracellular vesicles in the midgut epithelium
      stain intensely with wheat germ agglutinin reflecting the presence and sites of
      secretion and synthesis of chitin.

PMID- 18621275
TI  - Effects of ingested diflubenzuron on ovarian development during the sexual
      maturation of mealworms.
AB  - Diflubenzuron is the common name of the most potent insecticide belonging to
      benzoylphenyl urea group. This study describes the effects of orally administered
      diflubenzuron on ovarian development and structure in mealworms (Tenebrio
      molitor). Diflubenzuron was found to disturb growth and development of oocytes.
      It caused a decrease in both the number of oocytes per paired ovaries, the
      thickness of the follicular epithelium and the length of the basal follicles
      during the sexual maturation. However, it had no significant effect on the fine
      structure of follicular cells and basal oocytes examined in vitellogenic phase.
      These findings suggest that the reduction in fecundity, observed in several
      insect species by numerous others, is probably due to interference of
      diflubenzuron with the vitellogenesis via biochemical processes.

PMID- 18621276
TI  - Morphological characteristics of antennal sensilla in the European cornborer
      Ostrinia nubilalis (Lepidoptera: Pyralidae).
AB  - The European cornborer antenna is filiform in both sexes, but exhibits a
      substantially larger diameter in the males. On the antenna of both sexes, the
      following sensillum types were characterized: sensilla trichodea, s. basiconica,
      s. auricillica, s. coeloconica, s. chaetica and s. styloconica. Long dorsal
      bristles were of a chaetic type. An intermediate trichoid/basiconic type was
      found in low numbers on the ventral part of the antenna. In the male, three
      different morphological types of s. trichodea were observed, having one, two or
      three sensory cells, correlated with different dimensions of the hair. The s.
      trichodea with three sensory cells are most common in the basal part of the
      antenna, while sensilla with two cells are mainly found distally. Trichodea with
      one sensory cell are more evenly distributed over the length of the antenna. All
      cells present in the different s. trichodea respond to sex pheromone components
      or to a behavioural antagonist in electrophysiological sensillum recordings. S.
      basiconica and s. auricillica had 2-3 sensory cells, and a probable olfactory
      function. Sensilla coeloconica, also with a putative olfactory function,
      contained 3-5 sensory cells. S. chaetica of the taste/tactile type possessed 4 +
      1 sensory cells. S. styloconica comprised three sensory cells with possible
      functions as thermo- and hygroreccptors.

PMID- 18621277
TI  - Correlation between dendrite diameter and action potential amplitude in sex
      pheromone specific receptor neurons in male Ostrinia nubilalis (Lepidoptera:
      Pyralidae).
AB  - Outer dendritic segments of olfactory receptor neurons tuned to sex pheromone
      components were measured morphometrically on the antenna of male European corn
      borers. Ostrinia nubilalis, to determine if a correlation exists between the
      diameter of the outer dendritic segment and the spike amplitude. The olfactory
      sensilla investigated each contained three receptor cells. Two cells were each
      specific for one of the two pheromone components, (Z)-11-tetradecenyl acetate
      (Z11-14:OAc) and (E)-11-tetradecenyl acetate (E11-14:OAc). Two strains of
      cornborers (Z and E) differ as to which of the two pheromone components is the
      main one. In both strains a large difference could be observed between the spike
      amplitudes elicited in the receptor cells by the two pheromone components, the
      main component always eliciting the large spike. In F1-hybrids (EZ) of these two
      strains, producing both pheromone components in similar quantities, the spike
      amplitudes were equal in the two pheromone-specific receptor cells. The third
      cell responded specifically to a behavioural antagonist. (Z)-9-tetradecenyl
      acetate (Z9-14:OAc) in both the parental and hybrid strains, and always showed
      the smallest spike amplitude. In a morphometric study, the outer dendritic
      segments were shown to differ more in diameter between the largest and second
      largest cell in the two parental strains than in the hybrid strain, while the
      smallest diameter cell did not differ between the different strains. These
      results imply that receptor cells with larger diameter produce spikes with
      greater amplitude. The data also show that all three types of receptor neurons
      display outer dendritic segments with strong variation in the diameter along the
      length of the segment, and with a pronounced taper towards the tip.

PMID- 18621278
TI  - Ultrastructure of the symbionts and mycetocytes of bird cherry aphid
      (Rhopalosiphum padi).
AB  - As is known for other aphids, the symbiont cytoplasm in Rhopalosiphum padi is
      differentiated into a central eccentric and a cortical region which contains
      electron-lucent nucleoplasm and DNA fibrils. The cytoplasm is surrounded by a
      plasma membrane, cell wall and perisymbiotic membrane which are separated by
      periplasmic spaces. The periplasmic space between the cell wall and perisymbiotic
      membrane contains small vesicles. The symbionts are packed into mycetocyte cells
      which contain a large nucleus and all the normal cell organelles. For the first
      time, however microtubules and microfilaments have been identified, but only at
      high magnification and evidence has been found which makes it possible to propose
      a mechanism of vesicular transport.

PMID- 18621279
TI  - Localization of some neurotransmitters during developments in hydroidomedusae.
AB  - Neurotransmission in Cnidarians is known to occur mainly by peptidergic neuronal
      pathways; the role of cholinergic neurotransmission, that in other animals this
      involves both neurotransmission and developmental regulation, has never been
      shown with certainty. This histochemical-immunohistochemical study was performed,
      in different developmental stages of some hydroidomedusan species (characterized
      by different reproductive and developmental patterns) to investigate the presence
      and distribution of cholinesterase (ChE) activity, acetylcholine receptors,
      biogenic amines, and molecules immunologically related to secretory peptides
      (FMRF amide and VIP). The results showed that ChE (revealed by all the kinds of
      activities: AChE, PrChE, BuChE) is mainly present in developing or 'juvenile'
      structures. Biogenic amines are revealed by aldehyde-induced fluorescence at
      every stage studied, while peptide-like immunoreactivities are mainly present in
      differentiated structures. These findings support the hypothesis that all the
      chemical messengers here investigated arose very early in evolution, although, in
      some cases, with different functions. For most of the investigated species,
      similarities in the distribution pattern of markers generally reflect
      similarities in life cycle, rather than phylogenetic affinities.

PMID- 18621280
TI  - Morphological analysis of honeybee antennal cells growing in primary cultures.
AB  - A culture technique for the in vitro growth of antennal cells from honeybee is
      described. On the basis of morphological and immunocytochemical criteria, the
      cultured cells could be classified into neural and non-neural cells. Neural cells
      (type D) exhibited the main morphological features of insect olfactory receptor
      neurones (ORNs). Non-neural cells were large, flat cells that could be divided
      into three main types: Type A, B and C cells. Type A cells were spindle-like
      cells and resembled insect myocytes in culture. Type B cells were large cells
      with a veil-like cytoplasm. These cells tended to group and vacuolate towards the
      center of the cellular aggregate. Type C cells were either bipolar (Type C1) or
      multipolar (Type C2) flat cells which closely resembled insect glial cells in
      cultures.

PMID- 18621281
TI  - The eggshell of the almond wasp Eurytoma amygdali (Hymenoptera, Eurytomidae) - 1.
      Morphogenesis and fine structure of the eggshell layers.
AB  - The almond wasp Eurytoma amvgdali (Hymenoptera: Eurytomidae) feeds and oviposits
      exclusively in almonds and therefore is characterized as an insect of economic
      importance. Its meroistic polytrophic ovaries include follicles with a tri
      partite configuration. The mature follicles exhibit two filaments occupying the
      two poles of the egg. One is the micropylar filament while the other might serve
      for respiration since it is likely that its flattened end layers remain outside
      the almond fruit. The eggshell is formed by aposition and the follicle cells,
      which surround the follicle until the end of oogenesis, may be responsible for
      protein synthesis and secretion which finally lead to the assembly of the
      eggshell. The eggshell comprises the thin vitelline membrane, possibly a 'wax'
      layer of waterproofing function, a transluscent layer which appears amorphous
      even at the end of choriogenesis, a granular layer, including large and small
      electron-dense granules, and finally a columnar layer very similar to layers
      found in other insect species of the same or different orders. Peroxidase is
      histochemicalLY found for the first time in an eggshell of the Hymenoptera order:
      the tranluscent layer in particular is positively stained (electron-dense). Two
      possible roles of this peroxidatic activity are discussed, first, in comparison
      to other fruit-infesting insects, we assume that elastic chorion is produced
      through the function of peroxidase induced bonds (resilin-type bonds), very
      important for avoiding premature breaking, while being oviposited through a
      narrow ovipositor. Second, referring to other studies, this layer can play a
      bactericidal role for additional embryonic protection.

PMID- 18621282
TI  - The eggshell of the almond wasp Eurytoma amygdali (Hymenoptera, Eurytomidae) - 2.
      The micropylar appendage.
AB  - Micropylar apparatuses in insects are specialized regions of the eggshell through
      which sperm enters the oocyte. This work is an ultrastructural study and deals
      with the structure and morphogenesis of the micropylar appendage in the
      hymenopteran Eurytoma amygdali. The micropylar appendage is a 130 microm long
      cylindrical protrusion located at the posterior pole of the egg, unlike other
      insects i.e. Diptera. in which the micropylar apparatus is located at the
      anterior pole. In mature eggs there is a 0.4 microm wide pore (micropyle) at the
      tip of the appendage leading to a 6 microm wide micropylar canal. The canal
      contains an electron-lucent substance, it travels along the whole appendage and
      finally reaches the vitelline membrane of the oocyte. The vitelline membrane is
      covered by a wax layer and an electron-lucent layer, whereas the chorion
      surrounding the canal consists of a granular layer (fine and rough) and a
      columnar layer. The morphogenesis of the appendage starts in immature follicles:
      four central cells located at the posterior tip of the oocyte near the vitelline
      membrane, differing morphologically from the adjacent follicle cells. These
      central cells degenerate during early chorionic stages, thus assisting in the
      formation of the micropylar canal. The adjacent, peripherally located cells
      secrete the electron-lucent substance which fills the canal and at the same time,
      the fine granular layer is formed starting from the base towards the tip of the
      appendage. The secretion persists at late chorionic stages and results in the
      formation of the chorion around the micropylar canal. The extremely long
      (compared to other insects) micropylar appendage seems to facilitate the egg
      passage through the very thin and long ovipositor. The structure and
      morphogenesis of this appendage differs significantly from the micropylar
      apparatuses studied so far in other insects i.e. Diptera, and may reflect
      adaptational and evolutionary relationships.

PMID- 18621284
TI  - David Spencer Smith - a tribute.

PMID- 18621283
TI  - Hormones regulating structural changes in the adipocytes of the female earwig
      Labidura riparia.
AB  - Changes in periovarian fat body fine structure occur during the reproductive
      cycle of the female earwig Labidura riparia. During the process of
      vitellogenesis, high levels of protein synthesis are seen in the adipocytes.
      Simultaneously, the formerly osmiophilic lipid droplets become non-osmiophilic,
      while an osmiophilic material diffuses from lipid droplets to the cisternae of
      the rough endoplasmic reticulum (RER). These structural features alter during non
      vitellogenic periods: RER and Golgi apparatus regress and seem to be inactive.
      Lipid droplets are once again osmiophilic and no material enters into RER
      cisternae. Using microsurgical manipulations, hormonal treatments and light and
      electron microscopy, we have investigated the regulation of these changes. The
      neuroendocrine cerebral centre pars intercerebralis, by the action of the
      juvenile hormone of the corpus allatum. triggers protein metabolism. Another
      neuroendocrine center, the pars lateralis. and the hormone 20-hydroxyecdysone,
      regulate structural lipid droplet changes in the adipocytes.

PMID- 18621285
TI  - The effect of PH on fibrillogenesis of collagen in the egg capsule of the
      dogfish, Scyliorhinus canicula.
AB  - The collagen of the egg capsule of the dogfish, Scyliorhinus canicula is stored
      and secreted by the secretory cells of the D-zone of the nidamental gland
      (Rusaouen-Innocent, 1990b). The collagen appears to pass through several
      morphologically distinct textures during storage, secretion and fibril formation
      which may represent different lyotropic liquid crystalline phases (Knight et al.,
      1993). In the present communication we report evidence that a fall in hydrogen
      ion concentration induces fibrillogenesis during the secretion of the dogfish egg
      capsule. In an attempt to understand the factors involved in collagen assembly,
      we investigated the effects of subjecting isolated collagen storage granules in
      vitro to solutions ranging in pH from 2-11 and Na(+), K(+), Ca(++), Mg(++),
      Zn(++) and Cu(++) ions at concentrations varying from 0.01-0.5 M. From pH 2 to pH
      4 most granules appeared completely amorphous; from pH 5 to pH 7 granules showed
      the following previously reported liquid crystalline textures: isotropic,
      lamellar, micellar, hexagonal columnar, transversely banded twisted nematic, and
      unbanded twisted nematic. At pH 8 granules showed both the hexagonal columnar
      phase (phase IV) and small quantities of the final fibrillar phase together with
      a previously undescribed texture. The latter texture, which we refer to as phase
      VII, had a D period (17.5 nm) half that of the lamellar texture (phase II) and
      the final egg capsule fibrils (phase VI). From pH 9 to pH 11, only the final
      fibrillar texture (phase VI) together with small quantities of the new texture
      (phase VII) were present. Na(+), K(+), Ca(++), Mg(++), Zn(++) and Cu(++) ions did
      not appear to have an observable effect on the phases found in isolated granules
      at pH 7.0. The role of pH in collagen storage and fibrillogenesis was confirmed
      by direct estimation of the pH in vivo using vital staining with neutral red, a
      range of pH indicators applied to unfixed cryostat sections and direct
      measurements of the pH of the jelly within the egg capsule. The implications of
      these findings for the mechanism of collagen storage and fibrillogenesis in the
      dogfish egg capsule and other collagenous systems are discussed.

PMID- 18621286
TI  - X-ray microanalysis of ion contents in vacuoles and cytoplasm of the growing tips
      of a hydroid polyp as related to osmotic changes and growth pulsations.
AB  - Growth pulsations (GP) in hydroid polyps are associated with changes in vacuolar
      patterns which can be imitated by altering external osmolarity. With the use of X
      ray spectroscopy we measured the elemental contents in the vacuoles and cytoplasm
      of the growing tips of a hydroid polyp, Podocoryne carnea, under various tonicity
      conditions. Under hypertonic condition which arrested the samples at the
      retraction phase of normal GP, the elemental content within the vacuolar
      compartment appeared to be similar to that of the external medium, confirming our
      previous conclusion about the dehermetization of the vacuolar compartment under
      these conditions. Under hypotonical condition which arrested samples at the
      extension GP phase (vacuoles isolated) element ratio data displayed an obvious
      bimodality. At least one of the data groups could be characterized by a
      significant increase in the concentrations of sodium and potassium, as related to
      Cl, Ca and Mg, and in comparison to the same ratios in hypotonical samples and
      those in the external medium. We suggest that under hypotonical conditions the
      isolated vacuolar compartment is formed by influx of sodium and potassium ions.
      These cations are accompanied by anions other than chloride. Potassium appears to
      be transferred into the vacuoles from the cytoplasm while the sodium derives from
      the external environment.

PMID- 18621287
TI  - Germ cell cluster formation and oogenesis in the hymenopteran Coleocentrotus
      soldanskii.
AB  - During first stages of oogenesis in an ichneumonid wasp Coleocentrotus
      soldanskii. in each 32 cell cluster, as many as 8 cystocytes enter meiosis. Only
      one differentiates as an oocyte, the rest are gradually transdetermined to become
      nurse cells. Significantly, the nurse cells that have passed the first stages of
      meiosis retain some features characteristic of the oocyte. Namely the nuclei of
      these cells, as the oocyte nucleus, produce accessory nuclei (AN). Gradual
      transdetermination of pro-oocytes into nurse cells and the occurrence of ANs in
      transdetermined cells suggest that a diffusing substance, forming a concentration
      gradient, is responsible for the determination of the oocyte within the cystocyte
      groups in hymenopterans.

PMID- 18621288
TI  - Functional morphology of the subgenual organ of the carpenter ant.
AB  - Using light microscopy, confocal microscopy, electron microscopy and
      histochemistry, the subgenual organ (SGO) of an ant, Camponutas ligniperda, is
      investigated. Sensory units and attachment cells together enclose a large
      extracellular cavity, which is filled by acid mucopolysaccharides, as revealed by
      staining with ruthenium red. Due to this cavity, the whole SGO has the shape of a
      deformed sphere and the scolopidia exhibit a distribution of angles between 0
      degrees and 60 degrees with the tibial long axis (as is shown by phalloidin
      rhodamin staining of the actin filaments of the scolopale, viewed in situ by
      laser scanning confocal microscopy). The subgenual organ is innervated by a
      branch of the tibial nerve, which splits within or shortly distal to the femur
      tibia joint. The other features of the SGO of Camponotus ligniperda are similar
      as in other insects: the SGO of Camponotus ligniperda contains about 35
      scolopidial sensilla; it is fixed to the subgenual nerve on its proximal end, by
      its attachment cells to the opposite part of the cuticle; the fixation by the
      attachment cells is accomplished by a vast quantity of cytoplasmic microtubules;
      the construction of the sensory units is the same as in other mononematic
      scolopidial organs. The role of the extracellular lumen inside the organ and the
      special shape of the SGO of Camponotus ligniperda in mechanical transmission is
      discussed.

PMID- 18621289
TI  - Structural changes in the gill cells of Gammarus duebeni (Crustacea, Amphipoda)
      under osmotic stress; with notes on microtubules in association with the septate
      junctions.
AB  - The amphipod crustacean Gammarus duebeni (Lilljeborg) tolerates salinities in the
      range freshwater to seawater. Such tolerance requires the ability to respond to
      the varying degrees of osmotic stress imposed on the single layer of epithelial
      cells separating the outside medium from the haemolymph space in the gills.
      Following transfer of individuals from low salinities to seawater, changes occur
      in the fine structure of the epithelial cells. These changes involve the
      configuration of the apical border of the cells, the mitochondria and cytoplasmic
      lacunae. Despite such variation in cell organisation, the association between
      neighbouring epithelial cells appears unaffected. Attention is drawn to a well
      developed system of microtubules in association with the septate junctions. The
      possible mechanical role of these microtubules in protecting the integrity of the
      septate junctions from the effects of osmotically induced changes in cell volume
      is discussed.

PMID- 18621290
TI  - The female reproductive system of the eastern Australian scorpion.
AB  - The reproductive system of the female Urodacus manicatus (Scorpionidae) is
      described. Situated on the ventral side of the ovariuterus tubes are buds and
      diverticulae belonging to three developmental phases: (1) Bud-like, rudimentary
      diverticulae that will form future generations. (2) Embryonic diverticulae that
      will house the present generation. (3) Degenerating (= 'post-partum')
      diverticulae that contained the previous generation of juveniles just born. The
      smallest buds could be identified only by scanning electron microscopy of the
      ovariuterus tube. The various diverticulae were counted and their dimensions were
      measured. Based on the average number of the embryonic diverticulae, it appears
      that the average number of young that can be produced by a female during a single
      parturition is 16.8. This number does not appear to increase significantly with
      the growth of the female.

PMID- 18621291
TI  - Larval-adult oviduct transformation in an insect (Oncopeltus fasciatus):
      cytological study.
AB  - The lateral oviducts of the milkweed bug undergo a drastic larval-adult
      transformation during the last larval instar. This transformation is hormonally
      regulated and is connected with considerable morphological and cytological
      reorganization. Prior to transformation, the ducts are long and thin. The
      epithelial cells are fusiform with their long axes running cranial-caudal. They
      are tilted and slightly helically arranged. During transformation, the lateral
      oviducts shorten dramatically, the cells become columnar, and their long axes
      shift into the plane of cross sections. Whereas the cells appear cytologically
      uniform in the larval state, after transformation, the lateral oviducts are
      divided into a cranial secretory part, and a caudal part which exhibits a
      cuticular lining. Secretory processes and deposition of the cuticle start in the
      larva, immediately after transformation. Cuticle synthesis is first observed next
      to the common oviduct and progresses craniad. The cuticle-lined luminal surface
      reveals circular ridges and an intricate pattern of cteniform spines which are
      directed caudally. The novel mode of cell rearrangement during oviducal
      transformation and the functional significance of the two parts of the adult
      lateral oviducts are discussed.

PMID- 18621292
TI  - Colocalization of immunoreactivities to serotonin, calcitonin and CGRP in
      endocrine pulmonary cells of the iberian lizard Podarcis hispanica (Reptilia).
AB  - The coexistence of immunoreactivities to serotonin (5HT), calcitonin (CT) and
      calcitonin gene-related peptide (CGRP) was studied in pulmonary endocrine cells
      of the Iberian lizard by immunocytochemistry and in semithin/thin sections under
      light and electron microscope. Immunostaining of serial sections revealed
      coexistence of 5HT/CT/CGRP immunoreactivities in some cells, while in others only
      5HT/CT or CGRP immunoreactivities were found. Appropriate absorption controls
      excluded crossreactivity between the antisera used. Ultrastructurally, cells
      immunoreactive to 5HT/CT and CGRP share similar features, with round or slightly
      ovoid secretory granules of mean diameter from 165 to 180 nm. The possible
      functional significance of the copresence of 5HT, CT and CGRP is discussed.

PMID- 18621293
TI  - Cell types and evidences for traumatic cell death in a pressure-bearing tendon of
      Rana catesbeiana.
AB  - Tendon fibrocartilages appear in areas subjected to compressive forces. The
      bullfrog plantaris longus tendon was shown to be subjected to compression and to
      develop a modified region which differs from fibrocartilage in many respects.
      Ultrastructural analyses of the compression region of the bullfrog tendon
      demonstrated the existence of typical fibroblasts in the fibrous areas and large
      cells with abundant cytoplasm filled with intermediate type filaments. This large
      cell type has organelles restricted to a small perinuclear area or dispersed in
      the network of intermediate type filaments. Other cells were also found and
      exhibited less abundant deposition of intermediate filaments, showing an
      organization intermediate between fibroblasts and typical cells from the
      compression region. These intermediate type cells are closely associated with
      collagen bundles while the large cells seemed to have no connection with the
      fibrous components, but are immersed in a glycosaminoglycan-rich extracellular
      matrix. Aspects of cell death in association with extracellular matrix disruption
      were observed in some instances and it is likely that these are associated with
      traumatic stimulation of the tendon, especially when it is submitted to the
      sudden and strong mechanical loading expected to occur during jumping. Since the
      damage occurred mainly in cells of the intermediate type, it is assumed that
      accumulating intermediate type filaments is a protective mechanism against
      compressive forces to which this tendon is subjected.

PMID- 18621294
TI  - Editor's comment: quantitative morphology: a necessary component of modern
      anatomical research.

PMID- 18621295
TI  - Microtubule systems associated with the septate junctions of the gill cells of
      four gammarid amphipods.
AB  - The microtubular systems associated with the septate junctions of the gill
      epithelial cells of four species of gammarid amphipod are described. The four
      species examined included two relatively stenohaline marine forms, Chaetogammarus
      marinus and Gammarus locusta; a highly euryhaline species, Gammarus duebeni, and
      a stenohaline freshwater species, Gammarus pulex. Of these amphipods, G. locusta
      and C. marinus maintain only a limited osmotic gradient between their haemolymph
      and the medium and have a poorly developed junctional microtubular system; G.
      pulex has haemolymph which is some 300 mOsmol hypertonic to freshwater and has a
      well ordered system of microtubules on both sides of fairly long septate
      junctions; G. duebeni from brackish water tend to have a somewhat shorter length
      of septate junctions lined by one or occasionally by a double row of
      microtubules. The most complex junctional microtubular systems are shown by
      specimens of the freshwater race of G. duebeni celticus which have been
      acclimated to seawater. These can take the form of multiple arrays in which some
      microtubules are linked to the plasma membrane by dense strands. It is suggested
      that these findings are consistent with the hypothesis that one role of these
      microtubules is to provide mechanical stability to enable the integrity of the
      septate junctions to be maintained during osmotic stress.

PMID- 18621296
TI  - Three-dimensional reconstruction of glycosomes in trypanosomatids of the genus
      Phytomonas.
AB  - Computer aided three dimensional (3-D) reconstruction of cells from two isolates
      of protozoa of the genus Phytomonas, trypanosomatids found in plants, were made
      from 0.3 microm thick sections, imaged on a Zeiss 902 electron microscope with a
      energy filter for in ellastically scattered electrons, in order to obtain
      information about glycosomal shape diversity. Direct counts of peroxisomes
      (glycosomes) from Phytomonas sp. from Chamaesyce thymifolia indicated that there
      were fewer glycosomes per cell than the simple count of ultrathin section
      profiles would suggest and that these organelles could be long and branched. On
      the other hand, the stacked glycosomes observed in the isolate from Euphorbia
      characias were small individual structures and no connection was seen between
      them.

PMID- 18621297
TI  - Reappraisal of the pore channel system in the grooved pegs of Aedes aegypti.
AB  - Pore channels occur along the grooves of lactic acid-receptive grooved pegs on
      the antennae of female Aedes aegypti. There are about 38 pore openings per groove
      or about 456 per peg. This finding is in conflict with the previous report that
      pore channels were extremely rare. The pore channels are of a similar electron
      density to the cuticle of the peg, making them difficult to see. For this reason
      many of the pore channels were probably overlooked in the previous study. We
      could not find a terminal pore in the grooved peg as has been reported. Scanning
      electron microscopy and negative staining of the pegs revealed a tip of variable
      shape, usually without a pore. It is possible that 'edge effect' (more secondary
      electrons escape from edges of objects, making them appear brighter than central
      regions) leads to an apparent terminal pore. Occasionally pegs have a number of
      small (20-40 nm) pores in the tip region and these might also have been
      misinterpreted as a terminal pore. Pore channels appear to be the primary means
      of entry for air-borne stimuli in these grooved pegs.

PMID- 18621298
TI  - The localization of aluminium in the digestive gland of the terrestrial snail
      Helix aspersa.
AB  - The terrestrial snail Helix aspersa was exposed to food containing elevated
      levels of aluminium for up to 33 days and the digestive gland examined by light
      and electron microscopy and X-ray microanalysis. Four types of cell are found in
      the digestive gland, (digestive, excretory, calcium and thin) although aluminium
      was only found in the excretory cells. The aluminium was localised in the
      'yellow' or excretory granules that are a characteristic feature of the excretory
      cells. Aluminium was only found in the granules of snails fed aluminium but there
      was no difference in the appearance of granules from control or aluminium-fed
      snails. The granules were large (up to 20 mum in diameter), irregularly shaped
      and electron-dense. Sulphur, phosphorus and calcium were detected in granules
      from all snails. The presence of sulphur may indicate protein residues. The
      amount of aluminium and phosphorus in the granules increased over the
      experimental period but the number of granules did not change. Levels of
      aluminium in the granules decreased when the snails were given control food. The
      role of the excretory granules in the localisation, detoxification and excretion
      of aluminium is discussed.

PMID- 18621299
TI  - New aspects of the possible sites of ultrafiltration in annelids (oligochaeta).
AB  - Electron microscopic investigations of blood vessels were conducted to show sites
      of filtration such as podocytes or fenestrated endothelia. The endothelia of the
      blood vessels of Aelosoma hemprichi, Nais elinguis, Dero obtusa and Enchytraeus
      buchholzi consist of myoendothelial cells, chloragocytes and podocytes. The
      podocytes form large archs over a considerable area of the vessels. On the lumen
      side of the vessel there are several columnar processes which split into numerous
      small pedicels. The gaps between the adjacent pedicles are bridged by slit
      membranes. The podocytes are restricted to the front part of the ventral vessel.
      They are presumed to form a filtration surface. Furthermore, some parts of the
      ventral vessel are formed by a fenestrated endothelium, mainly in Enchytraeus
      buchholzi. In the vascular system of E. buchholzi two separate filtration sites
      were found. Additionally to the filtration site between ventral vessel and
      coelomic cavity a second filtration site was found in the front part of the body
      between blood sinus and coelomic cavity. In such areas the basement membrane is
      the only continuous layer between the blood vessel and the coelomic cavity. Its
      thickness is in the range of 40 nm. Possible filtration sites in the form of
      podocytes and irregular fenestrations could be localized at the border between
      the blood compartment and the coelomic compartment. It can be presumed that the
      primary urine may be formed by ultrafiltration of blood.

PMID- 18621300
TI  - Morphogenesis of the antenna of the male silkmoth, Antheraea polyphemus. V.
      Development of the peripheral nervous system.
AB  - The imaginal antenna of the male silkmoth Antheraea polyphemus is a feather
      shaped structure consisting of about 30 flagellomeres, each of which gives off
      two pairs of side branches. During the pupal stage (lasting for 3 weeks), the
      antenna develops from a leaf-shaped, flattened epidermal sac ('antennal blade')
      via two series of incisions which proceed from the periphery towards the
      prospective antennal stem. The development of the peripheral nervous system was
      studied by staining the neurons with an antibody against horseradish peroxidase
      as well as by electron microscopy. The epithelium is subdivided in segmentally
      arranged sensillogenic regions alternating with non-sensillogenic regions.
      Immediately after apolysis, clusters consisting of 5 sensory neurons each and
      belonging to the prospective sensilla chaetica can be localized at the periphery
      of the antennal blade in the sensillogenic regions. During the first day
      following apolysis, the primordia of ca. 70,000 olfactory sensilla arise in the
      sensillogenic regions. Axons from their neurons are collected in segmentally
      arranged nerves which run towards the CNS along the dorsal as well as the ventral
      epidermis and are enveloped by a glial sheath. This 'primary innervation pattern'
      is completed within the second day after apolysis. A first wave of incisions
      ('primary incisions') subdivide the antennal blade into segmental 'double
      branches' without disturbing the innervation pattern. Then a second wave of
      incisions ('secondary incisions') splits the double branches into single antennal
      branches. During this process, the segmental nerves and their glial sheaths are
      disintegrated. The axons are then redistributed into single branch nerves while
      their glial sheath is reconstituted, forming the 'secondary', or adult,
      innervation pattern. The epidermis is backed by a basal lamina which is degraded
      after outgrowth of the axons, but is reconstituted after formation of the single
      antennal branches.

PMID- 18621301
TI  - Morphogenesis of the antenna of the male silkmoth, Antheraea polyphemus. VI.
      Experimental disturbance of antennal branch formation.
AB  - In the male silkmoth Antheraea polyphemus, the formation of the side branches of
      the quadripectinate antennal flagellum was disturbed by an experimental
      manipulation. Normally the side branches develop in the pupa via deep incisions
      which proceed from the periphery towards the centerline of the leaf-shaped
      antennal anlage. Local removal of the uppermost, pigmented cuticular layers of
      the pupal antennal pocket ('cuticular window') led to a local standstill of
      branch formation in the manipulated region of the pocket, most probably caused by
      increased evaporation of water through the remaining layers of meso- and
      endocuticle. These parts of the antenna retained an unbranched, plate-like shape.
      This early morphogenetic stage was conserved by the secretion of antennal
      cuticle. Besides cuticle formation, development of sensilla is not impeded by the
      manipulation. In the plate-shaped regions, the initial pattern formed by the
      sensilla in the antennal epidermis is preserved, because they maturate at their
      birth places. In the individual segments, the pattern of sensilla shows a mirror
      like symmetry with respect to the segmental midline. From the edge to the
      midline, we found large s. trichodea, followed by small s. trichodea, s.
      basiconica, and s. coeloconica on the dorsal side whereas on the ventral side,
      there are only large s. trichodea and s. campaniformia. We conclude that the
      development of the featherlike antennal shape on the one hand and the development
      of sensilla and cuticle on the other hand are independent processes.

PMID- 18621302
TI  - Immunocytochemical localization of lysozyme in the nephrocytes of the harvestman,
      Leiobunum rotundum.
AB  - Nephrocytes are cells involved in the metabolism of hemolymph components and are
      characterized by peripheral finger-like projections bordering a labyrinthine
      channel system. The antibacterial protein lysozyme was localized in anterior and
      pericardial nephrocytes of the harvestman, Leiobunum rotundum, by biochemical and
      immuno-gold postembedding-labelling techniques. Lysozyme-activity was
      demonstrated in experimental animals, challenged by Micrococcus luteus Gram
      positive bacteria. With SDS-electrophoresis, lysozyme was proved to be present in
      nephrocytes adjoining the heart, before studies at the electron microscopical
      level were carried out. The opilionid lysozyme was found to have a molecular
      weight of 14,000 Da, thus belonging to the c-type lysozyme which is represented
      by hen-egg-white lysozyme. In untreated animals the presence of lysozyme could
      not be proved by electrophoresis. With immunogold labelling, however, lysozyme
      could be clearly localized in the vesicles of nephrocytes of untreated animals.
      Additional control experiments were carried out which revealed that the
      nephrocytes of L. rotundum in vivo are able to take up native lysozyme from an
      exterior medium. Therefore, the problem needs to be solved if nephrocyte vesicles
      transport lysozyme into or out of the cell.

PMID- 18621303
TI  - Improved enrichment of insect gap junctions by filtration and sonication of NaOH
      extracted subcellular fractions.
AB  - The purification of gap junctions from insects has been hampered by low yields
      when starting with dissected tissues or by contamination with non-junctional
      structures when starting with intact insects. A method is described here
      involving filtration and sonication of NaOH-extracted crude membrane fractions
      from larvae of the lepidopteran Heliothis virescens which yields fractions
      containing approximately 50% gap junctions and approximately 7 microg total
      protein per g of larvae and represents an estimated 10-100 fold increase in gap
      junction enrichment compared with a previously described procedure (Cell Tissue
      Res. 274: 393-403, 1993). The remaining structures in the fractions consist of
      non-junctional membrane, septate junctions, lamellate bodies and amorphous
      material.

PMID- 18621304
TI  - The interstitial cells of the trout testis (Oncorhynchus mykiss): ultrastructural
      characterization and changes throughout the reproductive cycle.
AB  - The major non-vascular cell types present in the interstitial compartment in
      trout testes have been ultrastructurally characterized and cell changes in the
      course of the two first reproductive cycles have been studied. Three major cell
      types are always present fibroblasts, myoid cells and Leydig cells. Their
      structure varies with the maturational stage of the gonad. Fibroblasts are
      centrally located in the interstitial areas. Numerous typical myoid cells are
      always present near the basal lamina. However, at the end of a cycle some of them
      display degenerative changes, then disappear. At the beginning of the next cycle,
      fibroblasts appear to differentiate to new myoid cells. Leydig cells present
      before the start of the first spermatogenesis are replaced by new ones which
      probably also arise from fibroblasts. These cells progressively differentiate
      during spermatogenesis, so that most of the Leydig cells present during the
      spermiation phase are fully-differentiated steroidogenic cells. At the end of a
      cycle, a certain number of the Leydig cells disappear and are replaced at the
      beginning of the next cycle by new ones most likely derived from fibroblasts. The
      remaining Leydig cells dedifferentiate to cells which may redifferentiate during
      gonadal activity. Macrophages are present mostly at the end of a cycle and
      participate at this time in the removal of dead interstitial cells. In
      conclusion, at least some fibroblast-like cells are precursor cells, able to
      replace myoid cells and Leydig cells which disappear between two consecutive
      reproductive cycles.

PMID- 18621305
TI  - Ultrastructural changes of the microvillar cytoskeleton in the photoreceptor of
      the crayfish Orconectes limosus related to different adaptation conditions.
AB  - In the retina of crayfish microvilli of seven of the eight photoreceptor cells
      build highly organized structures, the rhabdoms. Cytoskeletal elements inside the
      microvilli were investigated in conventional and slightly extracted electron
      microscopical preparations. In conventional preparations the ultrastructure of
      these cytoskeletal elements depended on the adaptational state of the animal.
      They appeared as central filament-like structures inside each microvillus when
      dark-adapted retinae were prepared and fixed at night in the absence of calcium.
      Changes of these conditions (light, daytime, or calcium concentration) impaired
      the detectability of these central filaments; in light-adapted eyes prepared at
      midday they were rarely seen. Nevertheless, single microvillar filaments were
      present in light-adapted retinae after mild cell permeabilization with the
      saponin beta-escin. They appeared as a regular structure in each microvillus,
      often attached to the membrane. Their fine structure was consistent with the
      ultrastructure of single actin filaments as indicated by fast-Fourier-analysis
      and further supported by the presence of anti-actin immunoreactivity in electron
      microscopical and immunocytochemical preparations. These results indicate that
      microvillar filaments are not necessarily destroyed by light as previously
      described; we suggest that their appearance inside the microvillus might be
      altered by the properties of associated, maybe sidearm-like proteins.

PMID- 18621306
TI  - The corpuscles of Stannius in arawana (Osteoglossum bicirrhosum), an ancient
      teleost.
AB  - The corpuscles of Stannius of arawana (Osteoglossum bicirrhosum), an ancient
      teleost, were examined by routine light and electron microscopy and following
      their immunoreactivity to salmon and trout stanniocalcin antisera. Periodic acid
      Schiff positive cells of the corpuscles of Stannius had a follicular arrangement
      and demonstrated a strong immunohistochemical reaction with both stanniocalcin
      antisera. Fine structural analysis of the paired, posteriorly located, and
      perirenal ovoid glands revealed two morphologically distinct cell types the basal
      laminae of which were ramified by nerve terminals. Immunocytochemistry
      demonstrated that osmiophilic secretory granules in both cell types were
      immunoreactive to the stanniocalcin antisera. When extracts of arawana corpuscles
      of Stannius were subjected to sodium dodecyl sulphate electrophoresis and Western
      blot analysis a diffuse molecular weight band was evident ( approximately 68 kDa)
      in the non-reduced condition. In all cases, immunoreactivity was abolished by
      preabsorption of the antisera with salmon stanniocalcin or with a crude extract
      of arawana corpuscles of Stannius. The corpuscles of Stannius of arawana are
      similar to those in more recent teleosts with respect to cell structure and their
      anatomical distribution but their stanniocalcin is more similar in molecular
      weight to that present in at least one other non-teleost actinopterygian (the
      gar) which has an ancient lineage.

PMID- 18621307
TI  - The sclerotized spermatophore of the barklouse Lepinotus patruelis.
AB  - Lepinotus patruelis Pearman (Psocoptera: Trogiidae) has a very unusual
      spermatophore that is a permanent, hardened structure which is deposited and
      retained in the spermatheca. This study elaborates on the structure of the
      spermatophore, shows for the first time that the spermatophore is sclerotized,
      and provides information on its composition and development over time. The
      spermatophore is produced within the ventral seminal vesicles, and transferred to
      the female as a semi-solid, bullet shaped object. It is composed of five lamina
      which undergo several transformations during the first 24 h after copulation. A
      sample of three newly formed spermatophores were found to contain 18, 40 and 55
      sperm. The possible function of the sclerotized spermatophore wall is discussed.

PMID- 18621308
TI  - Fine structure of the dorsal papillae in the holothurioid Holothuria forskali
      (Echinodermata).
AB  - The dorsal surface of the holothurioid Holothuria forskali bears several
      longitudinal rows of modified podia called papillae. Each papilla consists of a
      conical stem topped by an hemispherical bud. Their gross tissue stratification is
      the same all along the papilla being made up of four tissue layers, viz. an inner
      mesothelium, a connective tissue layer, a nerve plexus and an outer epidermis.
      The latter is differently organized according to whether it belongs to the stem
      or to the bud. The epidermis of the bud is built up by ciliated cells that
      intimately contact the nerve plexus and have the classical structure of
      echinoderm sensory cells. The papillae are thus sensory organs involved in
      mechanoreception and possibly chemoreception.

PMID- 18621309
TI  - A comparative microscopic and ultrastructural study of perichondrial tissue in
      cartilage of Octopus vulgaris (Cephalopoda, Mollusca).
AB  - The microscopic and submicroscopic structures of perichondrial tissues in the
      head cartilages of Octopus vulgaris were studied by polarized light and
      transmission electron microscopy. The orbital cartilages possess a birefringent
      layer parallel to the surface of the cartilage; ultrastructurally, this layer,
      which may be considered perichondrial tissue, has the typical organisation of
      connective tissue but does not possess the stratification of collagen laminae
      found in vertebrate perichondria. Perichondrial extracellular matrix is clearly
      distinct from that of cartilage because its collagen fibrils are of a larger
      diameter than collagen fibrils from cartilage. In addition, perichondrial
      fibroblasts are characteristically located at the center of collagen fibers. In
      the cerebral cartilage, the perichondrium is absent or discontinuous in relation
      to complex interconnections between cartilage and connective fibres, muscle
      fibres, blood vessels and nerve. Distinctive cartilage-lining cells, rich in
      electron dense cytoplasmatic granules, are stratified either along the cartilage
      surface or along vessels and muscle fibres that penetrate within the cartilage.
      The perichondrium of cephalopod cartilage, whose structure varies according to
      the location and function of its skeletal segments, mimics that of vertebrate
      perichondrium, exemplifying the high level of tissue differentiation attained by
      cephalopods.

PMID- 18621310
TI  - Fine structure and morphogenesis of the sclerite epicuticle in the Atlantic shore
      crab Carcinus maenas.
AB  - Three basic sublayers are identified in the epicuticle of the mineralised
      sclerites of the Atlantic shore crab Carcinus maenas (Crustacea, Decapoda): the
      surface coat, the cuticulin layer, and the inner epicuticle. Their morphogenesis
      and subsequent changes are described throughout the moulting cycle in the normal
      cuticle and the cuticular structures, namely the sensory bristles and
      epicuticular spines. At first, the cuticulin layer begins to form just after
      apolysis. This layer is built directly over the plasma membrane and immediately
      appears as a membrane-like structure 40 nm thick, composed of five symmetrically
      arranged laminae: two inner electron-lucent leaflets sandwiched between two thick
      electron-dense leaflets and separated by a thin dense median stratum. Elaboration
      of the inner epicuticle below the cuticulin layer is thought to occur via an
      intussusceptive process involving the pore canal cell extensions as transport
      routes. The inner epicuticle is made of vertically oriented microfibres embedded
      in an electron-dense matrix material. During the second half of the premoult
      period, the surface coat is deposited on the upper side of the cuticulin layer.

PMID- 18621311
TI  - Microstructural roughness of skeletal calcite in ophiuroid vertebral ossicles:
      evidence of wear?
AB  - Local areas of roughened skeletal calcite are reported from the otherwise smooth,
      imperforate skeletal articulations of the ophiuroid vertebral ossicle
      (Echinodermata: Ophiuroidea). Complementary patterns of roughness on both
      proximal and distal articulating surfaces suggest local points of wear between
      adjacent ossicles, presumably caused by repeated rotation of the intervertebral
      joint. This surface feature is discussed with respect to its possible origin
      (mechanical action, resorption of skeletal material, experimental artifact) and
      the functional morphology of the ophiuroid arm skeleton.

PMID- 18621312
TI  - Two different forms of gap junctions within the same organism, one with
      cytoskeletal attachments, in tunicates.
AB  - The cells of the intestinal tract and the stigmatal cells of the branchial basket
      have been studied in a range of tunicates including phlebobranch, aplousobranch
      and stolidobranch ascidians, as well as the doliolid and pyrosomatid thaliaceans.
      The intercellular gap junctions between gut cells appear conventional in thin
      section as do those found in the lower part of adjacent stigmatal cells. However,
      save for the stolidobranchs, the stigmatal cells also have a second kind of gap
      junction which exhibit an unusual fibrous density in association with their
      junctional cytoplasmic surfaces; these are found in the apical region of the
      cells. The fibrous density is particularly well demonstrated in specimens treated
      with tannic acid during fixation, and subsequent en bloc uranyl acetate staining.
      In the branchial basket the position of these apical gap junctions is at regular
      intervals between adhaering junctions, which have a more substantial
      paramembranous fibrous mat; these two kinds of junctions alternate along deeply
      undulating membrane appositions. With freeze-fracture, after chemical or cryo
      fixation, the gap junctions of the gut and those of the lower part of the
      stigmatal cells appear typical, with P-face connexons, while in the apical part
      of cells of the branchial basket the two faces of the gap junctions are very
      difficult to cleave apart. Frequently the P- and E-faces are found to adhere
      together in replicas, so that in these apical gap junctional regions, plaques of
      E-face with pits overlie the PF particles. In addition, regions of cytoplasm,
      into which the dense fibres project, often cleave over these adhaering E-faces of
      the apical gap junctions. The presence of these unusual gap junctional features
      in the apical region of the stigmata in the vicinity of cilia is discussed as
      regards their functional role.

PMID- 18621313
TI  - In vivo inhibition of vitellogenesis in the Dermapteran Labidura riparia by 20
      hydroxyecdysone.
AB  - In previous studies we have described the existence of cyclical changes in
      ecdysteroid levels during the female reproductive life of the earwig Labidura
      riparia. High levels of ecdysteroids are observed at the end of each vitellogenic
      period just before follicle degeneration, in coincidence with the beginning of
      each non-vitellogenic period. In the present work, using in vivo
      [(35)S]methionine incorporation, electrophoresis and electron microscopy, we
      study the effects on fat body and ovaries of 20-hydroxyecdysone (20E) injections
      into young vitellogenic females. This resulted in a reduction of proteosynthetic
      organelles (scarce Golgi complexes and fragmented RER cisternae), inhibition of
      vitellogenin synthesis in adipocytes, vitellogenesis arrest and premature
      follicular atresy. All these effects are suppressed when juvenile hormone
      treatment is associated with 20E injections. 20E does not inhibit vitellogenesis
      when applied to pars lateralis deprived females, which display continuous
      vitellogenesis. Thus, 20E does not act directly on ovaries nor on corpus allatum:
      the presence of the pars lateralis cells is required for 20E to inhibit
      vitellogenesis. These findings are explained in terms of the existence of a 20E
      feed back loop. This hormone acts via lateral neurosecretory cells of the brain
      which probably have an allatostatic effect.

PMID- 18621314
TI  - Dissociated neurons of the pupal blowfly antenna in cell culture.
AB  - Primary cell cultures are useful for studying the function of neurons in a
      simplified and controlled environment. We established a primary culture of
      antennal cells from pupal blowflies in order to investigate olfactory receptor
      neurons. In cultures, neuron-like cells were identified on the basis of
      morphology and immunocytochemical characterization with anti-HRP staining. Neuron
      like cells showed variety in the extension pattern of neurites. Many neuron-like
      cells extended a single prominent long process, which reached about 200 microm
      after four days, and several short ones. However, some neuron-like cells
      differentiated in other ways; some exhibited bipolar or multipolar processes,
      distinct from intact olfactory receptor neurons. The size of cell bodies of
      neuron-like cells as divisible into two groups; approx. 7 microm diameter and 10
      15 microm diameter. Neuron-like cells in culture will provide a good model for
      electrophysiological analysis and for developmental studies of olfactory receptor
      neurons.

PMID- 18621315
TI  - Oogenesis in Actinoposthia beklemischevi (Platyhelminthes, Acoela): an
      ultrastructural and cytochemical study.
AB  - The oogenesis of the acoel Actinoposthia beklemischevi can be divided into a
      previtellogenic and a vitellogenic stage. Maturing oocytes are surrounded by
      accessory cells (a.c.) that produce electrondense granules, the content of which
      is released into the space between the oocyte and a.c. and gives rise to a thin
      primary egg envelope. The a.c. may also contribute to yolk synthesis by
      transferring low molecular weight precursors to the oocyte. Two types of
      inclusion are produced in maturing oocytes. Type I inclusions are small, roundish
      granules produced by the Golgi complex. They have a proteinaceous non
      polyphenolic content which is discharged in the intercellular space and produce a
      thicker secondary egg envelope. Type I inclusions represent eggshell-forming
      granules (EFGs). Type II inclusions are variably sized globules progressively
      changing their shape from round to crescent. They appear to be produced by the
      ER, contain glycoproteins and remain scattered throughout the cytoplasm in large
      oocytes. Type II inclusions represent yolk. The main features of oogenesis in
      Actinoposthia are: (a) EFGs have a non-polyphenolic composition; (b) the egg
      envelope has a double origin and is not sclerotinized; (c) yolk production
      appears to be autosynthetic. The present ultrastructural findings are compared
      with those from other Acoelomorpha and Turbellaria.

PMID- 18621316
TI  - Pereopodal disk: a new type of extrabranchial ion-transporting organ in an
      estuarine amphipod, Melita setiflagella (crustacea).
AB  - A discoid organ, 'pereopodal disk (PD)', was found on the medial surface of the
      basipodite of each pereopod, except the third and the fourth, in an estuarine
      amphipod, Melita setiflagella. The silver methods showed that PD is an
      extrabranchial ion-permeable area of the body surface. The ultrastructural study
      revealed that PD is covered by a thin and soft cuticle layer suggesting high
      permeability to gases and ions, and is composed of a thick, transporting-type
      epithelium. This epithelium is characterized by deep basal infolding systems
      (BIS) of cell membranes exceeding two-thirds of the epithelial thickness and
      complicated interdigitations between adjacent epithelial cells, both associated
      with many mitochondria. Apical infolding systems (AIS) are shallow and not
      accompanied by any mitochondria. These characteristics resemble those of the
      sternal epithelia and form a striking contrast in the polarity of the infoldings
      to the gill epithelia, which are characterized by a well-developed AIS and sparse
      BIS. The results suggest that this unique organ may be involved in the active
      transport of electrolytes to maintain constant osmotic pressures of the body
      fluids under widely fluctuating salinities of the estuarine environments.

PMID- 18621317
TI  - The infrared receptor of Melanophila acuminata De Geer (Coleoptera: Buprestidae):
      ultrastructural study of a unique insect thermoreceptor and its possible descent
      from a hair mechanoreceptor.
AB  - The paired infrared organs of Melanophila acuminata consist of 50-100 sensilla
      situated at the bottom of a pit next to the coxae of the mesothoracic legs, where
      no exocuticle is developed. Each sensillum is accompanied by a wax gland and has
      a cuticular lens-like spherule (diameter 12-15 microm) bulging out with its upper
      hemisphere above the surface, covered only by a thin cuticle of about 1 microm.
      Distal processes of two enveloping cells surround the entire spherule in the form
      of a flattened protoplasmatic layer with the exception of a small apical stalk
      connecting the spherule to the outer cuticle. The spherule is innervated by a
      single sensory neuron of the ciliary type which is anchored ventrally with the
      distal tip of its cylindrical and unbranched DOS in the spherule. The insertion
      of the dendrite, which contains a well-developed tubular body, is always
      eccentric like in a hair mechanoreceptor (sensillum trichodeum) and there is no
      evidence of any optical function of the spherule. Three enveloping cells exist,
      but only one - probably the trichogen cell - forms a relatively small outer
      receptor lymph cavity. In the posterior wall of the pit - where exocuticle is
      developed - so-called suppressed systems can be found which remain completely
      below the cuticle with their otherwise well-developed spherules. Additionally,
      there is a tendency towards basally flattening and longitudinally stretching of
      spherules which are situated more peripherally. They strongly resemble the basal
      regions of hair mechanoreceptors (sensilla trichodea) in their immediate
      neighbourhood which are also accompanied by wax glands. Because of the existence
      of these transitional stages and the great ultrastructural resemblance between
      infrared receptors and hair mechanoreceptors concerning the bauplan of the
      sensory neurons and their mode of innervating the cuticular apparatus, we
      conclude that the infrared sensilla are probably derived from hair
      mechanoreceptors. Based on these results and transmission measurements of
      infrared radiation through the cuticular components of the organ, a model of the
      possible function of the infrared receptor is presented.

PMID- 18621318
TI  - Impact of glutaraldehyde versus glutaraldehyde-formaldehyde fixative on cell
      organization in fish corneal epithelium.
AB  - The purpose of this study was to examine the impact of a low osmolality
      glutaraldehyde fixative and a high osmolality glutaraldehyde-formaldehyde
      fixative on the structural organization of a tissue that could be exposed to low
      and high osmolality environments. The corneas of freshwater trout were prepared
      for transmission and scanning electron microscopy using either a fixative of 2%
      glutaraldehyde in 60 mM cacodylate buffer (pH 7.8, 260 mOsm/l) or a fixative
      prepared by adding 2.5% glutaraldehyde to a solution of 1% formaldehyde and
      buffering the solution with 0.1 M cacodylate (pH 7.6, 850 mOsm/l; Karnovsky-type
      fixative). The corneal epithelial cell layer thickness was greater after
      glutaraldehyde compared to glutaraldehyde-formaldehyde fixation (67 vs 55
      microm), as was the thickness of the superficial cells (5.1 vs 3.4 microm) and
      basal cells (43 vs 38 microm). The intermediate (wing) cells of the epithelium
      were, however, less thick after glutaraldehyde fixation (15 vs 18 microm). The
      width of the squamous, intermediate and basal cells was greater following
      glutaraldehyde fixation with the effect being greatest in the superficial layers
      and insignificant at the level of the basal cells. The results show that chemical
      fixatives with extremes of osmolality cannot only produce different cell sizes in
      a tissue but also determine the overall organization of the cells in a positional
      dependent fashion.

PMID- 18621319
TI  - Localization of connectin-like proteins in leg and flight muscles of insects.
AB  - In leg muscle sarcomeres of a beetle, approximately 6 mum sarcomere length at
      rest, projectin ( approximately 1200 kDa) was located on the myosin filament up
      to 2 mum from the both ends of the filament, using immunofluorescence and
      immunoelectron microscopy. On the other hand, projectin linked the Z line to the
      myosin filament and bound on the myosin filament in beetle flight muscle,
      approximately 3-4 mum sarcomere length at rest. Connectin-like protein (
      approximately 3000 kDa) was detected by immunoblot tests in beetle, bumblebee and
      waterbug leg muscles. Immunofluorescence and immunoelectron microscopic
      observations revealed that the connectin-like protein linked the myosin filament
      to the Z line in beetle leg muscle.

PMID- 18621320
TI  - Moulting of mechanoreceptive hair sensilla of Lepisma saccharina (Zygentoma) and
      Machilis spec. (Archaeognatha).
AB  - In all insects investigated hitherto the mechanoreceptive hair sensilla possess
      the same organization plan. There are differences in the moulting process of
      hemimetabolous insects. While the functions of the three enveloping cells are
      corresponding, the position of the moulting porus is different. In Gryllus and
      Periplaneta the moulting porus is situated at the base of the hair, in Machilis
      25 mum above the base of the hair. In Lepisma, however, the moulting porus is
      located at the tip of the hair shaft. Comparison of mechanoand
      contactchemoreceptive hair sensilla shows that the position of the moulting porus
      in primitive ectognathous insects represents an argument for the close
      morphological and phylogenetical relationship between both types of sensilla.
      Interpreting our results, the original position of the moulting porus is at the
      tip of the hair sensilla. In mechanoreceptors, where the moulting porus is
      located at the base of the hair, the original tip of the hair (position of the
      moulting porus) is overgrown at the side by a 'secondary hair process'.

PMID- 18621321
TI  - Cerebral extraocular photoreceptors in ants.
AB  - Clusters of dark pigmented cells, called putative cerebral extraocular
      photoreceptors (CEPs), are described in the optic lobes of four ant species: Atta
      sexdens, Camponotus rufipes, Camponotus crassus, and Pseudomyrmex adustus.
      Electron-micrographs of CEPs show a central rhabdom-like structure formed by
      tightly interleaved cells containing shielding pigments, with axons projecting
      toward the outer optic chiasm. The presence of a great number of mitochondria,
      nucleolus, and multivesciular bodies suggests that these clusters might be
      functional extraocular photoreceptors. Although some branches from GABA-like
      immunoreactive neurones occur near the CEP region, GABA-immunoreactivity was not
      detected in CEPs. The ant's cephalic cuticle blocks short wavelengths (< 500 nm)
      and the light transmittance is less than 20% for wavelengths between 500-700 nm.
      Ant species with both diurnal and nocturnal habits and heightened nocturnal
      visual sensitivity (A. sexdens and C. rufipes) contain more CEPs than those with
      diurnal habits and lower visual sensitivity (C. crassus and P. adustus). The
      reduction of light reaching this putative extra-ocular system could act as a
      signal for a circadian pacemaker and, as a possible consequence, lead to an
      increase of nocturnal visual sensitivity of the compound eyes and/or nocturnal
      locomotor activity, as already observed in the species studied.

PMID- 18621322
TI  - Fine structure of cells specialized for secretion of aggregation pheromone in a
      nitidulid beetle Carpophilus freemani (coleoptera: Nitidulidae).
AB  - The cells that secrete the aggregation pheromone of the male nitidulid beetle
      Carpophilus freemani are exceptionally large and lie within the body cavity.
      These secretory cells share many ultrastructural features with cells of other
      pheromone and defense glands, but they also have several unique features. A deep
      invagination of the surface of each of these cells acts as the secretory surface
      for the pheromone. The invaginated surface is highly convoluted and surrounds a
      narrow cuticular ductule that is connected to the tracheal system. This surface
      is not covered with microvilli as the comparable surfaces are in other insect
      secretory cells. Each secretory cell is filled with an abundance of lipid spheres
      that presumably contain precursors for the pheromone. Examining cells from
      beetles producing different levels of pheromone showed that sizes of secretory
      cells are positively correlated with rates of pheromone production. Whereas
      secretory and ductule cells of other insect glands are usually epidermal cells,
      these cells of nitidulid beetles represent the first pheromone glands in which
      oenocytes are believed to have been recruited for pheromone production and
      tracheal cells have been recruited as ductules for these cells.

PMID- 18621323
TI  - Neuronal pathways of three neurosecretory cells from the lateral lobes in
      Helisoma (Mollusca): innervation of the dorsal body.
AB  - The neurite distribution of three large neurosecretory cells, namely one canopy
      cell and two lateral-lobe cells from each lateral lobe of the cerebral ganglia in
      Helisoma duryi were studied by thick and thin plastic serial sections. These
      cells from only the right lateral lobe innervate the dorsal body. Neurites from
      the canopy cell innervate the cell-bodies whereas those from the lateral-lobe
      cells innervate the cell-processes of the dorsal body. Neurosecretory granules
      from these neurites are released at their sites of innervation. The neurites of
      the optic nerve form synapses with lateral-lobe cell(1), and synapse-like
      contacts with lateral-lobe cell(2) while a neurite of each canopy cell is found
      within its collateral optic nerve. Based on the anatomy of the lateral-lobe nerve
      cells and the optic nerve, it is argued that the stimulatory effect of long days
      on the dorsal body and on egg production is mediated through the lateral-lobe
      cells and the canopy cell.

PMID- 18621324
TI  - The antenna cleaner gland in Messor rufitarsis (hymenoptera, formicidae).
AB  - TEM and SEM analysis of the tibio-tarsal antennal cleaner in Messor rufitarsis
      reveals a pore region on the surface of the basitarsus. These pores are
      originating from a cluster of highly prismatic epidermal cells that fill the
      anterior hemolymph space of the leg almost completely. Within the cytoplasma of
      the cells, basal labyrinth, nucleus/rough endoplasmic reticulum, 'secondary
      lysosomes', a lot of smooth endoplasmic reticulum and distal microvilli regions
      can be distinguished indicating that the cells are 'class I' gland cells. Their
      secretion appears to be transported to the antennal cleaner apparatus via a
      subcuticular space and pores. It is suggested that the secretion might be used
      for cleaning of the antenna and/or chemical communication. SEM examination of six
      additional species indicates that an antennal cleaner gland might be present
      throughout the ants.

PMID- 18621325
TI  - Yakov a. Vinnikov 85!

PMID- 18621326
TI  - Sugarcane somatic embryogenesis: a scanning electron microscopy study.
AB  - Spindles of CUBA 87-51 sugarcane were cultured in Murashige and Skoog (MS) basal
      medium and supplemented with different nutrients. Embryogenic and non-embryogenic
      callus obtained were comparatively studied by scanning electron microscopy (SEM).
      Samples of embryogenic callus cultured in regeneration medium (MS without 2.4
      dichlorophenoxyacetic acid) were taken at different times for analyzing the
      sequential process. Distinctive features of two types of callus are shown by SEM:
      cells organized in embryos are noted in embryogenic callus; while elongated,
      disorganized cells can be seen in non-embryogenic callus. The characteristics of
      the embryos during plant regeneration are described. Sugarcane embryoid stages
      are: globular, globular with lateral notch and scutellum. In this process also
      appear shoot meristems, leaf and root primordia and finally, true leaves and
      roots. It is concluded that callus plant regeneration from young leaf segments of
      sugarcane mainly occur via somatic embryogenesis.

PMID- 18621327
TI  - Antibodies to alpha-fetoprotein disrupt histogenesis in cultured chick retinae.
AB  - alpha-Fetoprotein (AFP) is an oncofetal antigen believed to play an important
      role in normal development and carcinogenesis but very little is known about such
      a role. We have investigated here the role of AFP in neural retina development by
      selectively neutralising AFP in vitro. AFP has been immunohistochemically located
      in different cells and layers of the retina during its development, 4-day-old
      embryos being the earliest developmental stage when AFP is detected in the
      growing ganglion cell layer. Seven-day-retinae treated with antibodies to AFP in
      organ culture for 3 days did not continue to develop in the same way that they do
      in the egg. Neither the plexiform layers nor the buds of photoreceptor cells were
      observed after this culture period. In contrast, 7-day retinae cultured in the
      presence of non-immune serum developed in a manner similar to retinae in ovo. We
      present here the first evidence, derived by selectively blocking AFP in vitro
      with specific antibodies for an essential role of AFP in the normal development
      of the chick retina.

PMID- 18621328
TI  - Light and electron microscopy study of the salivary gland secretory cells of
      Helicoidea (Gastropoda, Stylommatophora).
AB  - We have studied the secretory goblet-cells of the salivary gland of six species
      of Helicoidea: Elona quimperiana, Trissexodon constrictus, Hygromia limbata,
      Cernuella aginnica, Cepaea nemoralis and Helix aspersa, using light microscopy
      and transmission electron microscopy. In each of the species studied, we have
      been able to demonstrate the presence of four cell types. Following a comparative
      study with the goblet-gland cells present in the six species in question, and the
      comparison of our data with previously published reports on the entire set of
      Stylommatophora, we have established the homologies corresponding to the cell
      types observed. Our hypotheses were based primarily on the morphology of the
      rough endoplasmic reticulum and of the secretory vesicles. Accordingly, we have
      defined five cell types for these six species. The first three cell types, A, B
      and C, appear in the six species studied and seem to be present in all the
      stylommatophores. In order to standardize the terminology used by the different
      authors, we propose that these cell types be called: 'swollen RER cisterns
      mucocyte', 'granular mucocyte' and 'alveolar cell', respectively. The D-cell type
      or 'basophilous cell' is present only in Hygromia limbata, Cernuella aginnica,
      Cepaea nemoralis and Helix aspersa. The E-cell type or 'vacuolated cell' appears
      only in Elona quimperiana and Trissexodon constrictus.

PMID- 18621329
TI  - The ocelli of arctiid moths: ultrastructure of the retina during light and dark
      adaptation.
AB  - The ultrastructure of the dorsal ocelli of two arctiid moths (Arctia caja (A.
      caja) and Creatonotos transiens (C. transiens) was investigated. The two ocelli
      are positioned laterally on the vertex of the head posterior to the antennae,
      close to the dorsal margin of the compound eyes. The biconvex corneal lens is
      located at the apex of a cone-shaped cuticular elevation, which encapsulates the
      retina. The corneagenous cell layer and the cup-like retina with about 100-130
      receptor cells in A. caja (70-90 receptor cells in C. transiens) are adjoined
      proximally. The retina is completely enclosed by the perineurium and thus
      separated from the corneagenous cells and the surrounding hemolymph. Irregularly
      shaped rhabdomeres, consisting of densely packed microvilli, are present in the
      distal region of the receptor cells. Up to three cells may form a rhabdom. Thus a
      loose network of photoreceptive structures over the whole retina results. A
      unique feature of these arctiid ocelli are photoreceptor vacuoles containing
      microvilli. The function of these organelles is unknown. The rhabdomeric
      arrangement within the light and dark adapted retina differs considerably. The
      ultrastructure of the rhabdomeres indicates an intense membrane turnover.
      However, changes in adaptation state are not accompanied by dramatic changes in
      the photoreceptive area of an ocellus.

PMID- 18621330
TI  - Epixenosomes: peculiar epibionts of the ciliate Euplotidium itoi: morphological
      and functional cell compartmentalization.
AB  - As already reported, epixenosomes have a complex cell organization although they
      lack membranous organelles and a nuclear envelope. Different morphological
      compartments have been evidenced: (1) a space (IM) between the 2 external
      membranes in which acid phosphatase has been observed; (2) an apical,
      electrondense zone (DZ) not delimited by a membrane or thin envelope, containing
      DNA and basic proteins; (3) a roundish body (RB), 200 nm in diameter, containing
      reserve polysaccharides and enzymes, in particular, peroxidase; (4) an extrusive
      apparatus (EA) consisting of a ribbon with smooth surfaces in which lectin
      binding sites are present, and immersed in a complex matrix different from the
      remaining cytoplasm. Along its internal and external limits, active adenylate
      cyclase has been evidenced. At its top, a 'ring' of peroxidase is present; (5) a
      basket surrounding the extrusive apparatus probably consisting of tubulin
      microtubules. The cytochemical data, especially the precise localization of the
      enzymes shown here, indicate that in epixenosomes, a functional
      compartmentalization corresponds to a structural complexity, in spite of the
      absence of internal true membranes.

PMID- 18621331
TI  - Giant secretory granules in the ducts of the parotid and submandibular glands of
      the slow loris.
AB  - The parotid and submandibular glands of a slow loris, a rare Southeast Asian
      primate, were obtained after the head had been perfused by fixative for a study
      of the brain. These tissues were processed by conventional means for electron
      microscopy. Glands also were obtained at autopsy from 2 other lorises, fixed by
      immersion in formalin, and subjected to a battery of tests for glycoconjugates.
      In the parotid gland, a short segment of the proximal striated duct lacks both
      basal striations and any sign of secretory activity. The major portion of the
      striated duct consists of tall cells that contain a spectrum of secretory
      granules, some larger than the nuclei (many granules are > 9 mum in diameter).
      These granules, which are delimited by a single membrane, are capable of chain
      exocytosis. Many of the giant granules have bundles of cytofilaments (4.5-6.5 nm)
      in apparent association with their surface. Occasional cells contain numerous
      small granules. Duct cells with or without granules lack basal striations. The
      granules contain neutral glycoconjugates but no acidic glycoconjugates. Some, but
      not all, interlobular excretory ducts also have secretory granules that run the
      gamut from tiny to giant. Exactly the same situation occurs in the submandibular
      gland. Unlike other primates, which may have duct cells that contain only a few
      tiny granules in their apices, the cells in both the striated and excretory ducts
      in the slow loris appear to be specialized for secretion rather than for
      transport. The biofunction of the giant granules is unknown.

PMID- 18621332
TI  - The sperm structure of the gall-midges Anaretella and Lestremia (Insecta,
      Diptera, Cecidomyiidae).
AB  - The sperm structure of some dipteran flies belonging to the Lestremiini tribe
      have been examined. Anaretella cincta was shown to have an axoneme made of 20-21
      microtubular doublets, disposed in a circle in a cross section and surrounding a
      mitochondrion. Other crystal-containing mitochondria flank the axoneme; a second
      species (Anaretella sp.) was provided with 21-22 axonemal doublets. Lestremia is
      characterized by a flattened axoneme, consisting of about 150 doublets arranged
      in 2 antiparallel rows and surrounding a few mitochondria. These mitochondria, in
      Lestremia sp., have a crystalline core that is missing in Lestremia cinerea. The
      structure of microtubular doublets is quite similar in the 2 related genera and a
      derivation of the flattened axoneme found in Lestremia from that circular of
      Anaretella is suggested. Sperm structure suggests that Lestremia cinerea is not a
      uniform species.

PMID- 18621333
TI  - Time-course of apoptosis in the olfactory epithelium of rainbow trout exposed to
      a low copper level.
AB  - Copper at low doses is known to specifically induce olfactory neuron death in
      fish olfactory epithelium. Using light and electron transmission microscopy, we
      have investigated the features and the time-course of receptor cell death in
      rainbow trout exposed for 15 days to 20 mug Cu(2+)/l. Ultrastructural
      observations demonstrate that degenerating cells, which included both mature and
      immature neurons, exhibited morphological changes characteristic of a cell death
      by apoptosis. Quantitative analysis shows that the number of apoptotic cells
      increased significantly already after 1 day of exposure, reaching a peak at day
      5. From this timepoint of exposure, no more mature neuron was noted in the
      olfactory epithelium. Following a significant decrease in the number of apoptotic
      cells at day 10, a second wave of neuron death was noted at day 15. These
      findings argue for the occurrence of a neurogenesis process to balance the
      receptor cell death, despite continued copper exposure, and for a higher
      vulnerability to the metal of olfactory neurons presenting more advanced stages
      of cell differentiation. The molecular mechanisms by which copper may induce
      olfactory neuron apoptosis are discussed.

PMID- 18621334
TI  - Zinc metalloprotease activity in the cement precursor secretion of the barnacle,
      Chthamalus fragilis Darwin.
AB  - Adult barnacles, Chathamalus fragilis, were removed carefully from the leaves and
      stems of marsh grass and floated base-up in algae-supplemented sea water. During
      the next 24-72 h, the animals secreted onto their exposed bases, a fluid, the
      cement precursor secretion (CPS), aliquots of which were collected in glass
      micropipets and pooled. The concentration of protein in pooled samples of CPS
      averaged 1.5 g +/- 0.42 protein/l of secretion. Protease activity was expressed
      as A(492) units/h/g of CPS protein. Aliquots of 5-45 l of pooled CPS samples,
      incubated in the presence of FTC-casein at 37 degrees C for 24 h, exhibited 8.31
      x 10(-5) +/- 1.55 x 10(-5) DeltaA(492) units/hr/g of protein on average. Protease
      activity was optimized by the addition of 10 mM Ca(++) ions. Activity was
      detectable over a broad pH range, but was optimal around pH 8. Protease activity
      was inhibited up to 40% in the presence of 2.7 mM ethylenediaminetetraacetic acid
      (EDTA) and up to 97% in the presence of 2.5 mM 1,10-phenanthroline (OP) in the
      presence of 10 mM Ca(++) ions. Although low concentrations of Zn(++) ions (10 M)
      had little effect on protease activity, higher concentrations of Zn(++) ions (50
      M to 15 mM Zn(++)) inhibited CPS protease activity. Protease activity was not
      inhibited by 1 mM phenylmethylsulfonylfluoride (PMSF), nor by 28 M E64, nor by 20
      M leupeptin. At the present time, the protease activity in the barnacle CPS may
      best be characterized as a Ca-stimulated Zn-metalloprotease.

PMID- 18621335
TI  - Cell growth patterns and lens geometry: a quantitative study from three
      dimensional reconstructions.
AB  - The growth of the lens of the sea lamprey, Petromyzon marinus, was studied over
      the 5 years of larval development. Whole lenses (25) and Golgi-impregnated cells
      (393) were reconstructed with computer-assisted microscopy. Several cellular
      geometric parameters (length, width, curvature, surface, volume, shape) were
      correlated with the position of the cell's base on the lens capsular perimeter.
      Based on these correlations, the cells formed four groups that correspond to the
      central anterior, germinative, transitional and cortical fiber zones. A fifth
      zone, containing nuclear fiber cells, never stained. Lens growth is exponential
      during the 5 years. The anterior epithelium increases in size and in cell number
      by cell growth and division. The posterior mass increases in cell number by
      recruitment and increases in size by cell growth. A model is proposed to account
      for the size and shape of the lens based upon the coupling of anterior and
      posterior growth patterns. Four zonal boundaries are defined by changes in cell
      growth patterns. With growth, cells are subsumed into adjacent zones and zonal
      boundaries move away from the lens center. We find no support for the suggestion
      that cells migrate centrally.

PMID- 18621336
TI  - Ultrastructural adaptations for viviparity in the female reproductive system of
      gyrodactylid monogeneans.
AB  - The female reproductive system of viviparous monogeneans (Gyrodactylus and
      Macrogyrodactylus) has been examined using fluorescence microscopy and
      transmission electron microscopy. The female system is tubular, made up of a thin
      walled proximal seminal receptacle/ootype and a distal uterus, separated by a
      complex cellular region. Both parts have a continuous syncytial cytoplasmic
      lining. Maturing oocytes in the seminal receptacle/ootype are in intimate contact
      with the receptacle lining. The uterus cytoplasmic lining completely surrounds
      the developing embryo, and is continuous with anterior and posterior cell bodies
      which fluoresce strongly when stained with bisBenzimide. This lining is most
      extensive around small embryos, when it contains specialised organelles including
      star-shaped configurations of electron-dense membranes and multilamellate bodies.
      Pits in the uterus wall bridged by membranous structures connect the cytoplasmic
      lining to parenchyma or digestive cells. The cytoplasmic lining regresses as the
      embryo develops, but remains continuous and in intimate contact with the
      embryonic tegument (at least until the near-term embryo begins independent
      movement). Numerous ribosomes, membranes and mitochondria in the uterine
      cytoplasmic layer indicate a high metabolic rate, and exo/endocytotic vesicles in
      the F1 tegument suggest transfer of materials occurs between parent and embryo.
      Putative vitelline cells in the posterior of the body contain abundant RNA,
      ribosomes and membrane-bound secretory bodies, and are filled with an electron
      lucent secretion. However, there are no ducts associated with these cells, and
      their function remains unknown. The cytoplasmic lining of both the seminal
      receptacle/ootype and the uterus appears to regulate oocyte/embryo nutrition.
      Similar syncytial layers occur in rotifers, but are unlike the nutritive
      epithelia of most other viviparous organisms.

PMID- 18621337
TI  - A novel adhering junction in the apical ciliary apparatus of the rotifer
      Brachionus plicatilis (Rotifera, Monogononta).
AB  - Cultures of the rotifer Brachionus plicatilis were examined with regard to their
      interepithelial junctions after infiltration with the extracellular tracer
      lanthanum, freeze-fracturing or quick-freeze deep-etching. The lateral borders
      between ciliated cells have an unusual apical adhering junction. This apical part
      of their intercellular cleft looks desmosome-like, but it is characterized by
      unusual intramembranous E-face clusters of particles. Deep-etching reveals that
      these are packed together in short rows which lie parallel to one another in
      orderly arrays. The true membrane surface in these areas features filaments in
      the form of short ribbons; these are produced by projections, possibly part of
      the glycocalyx, emerging from the membranes, between which the electron-dense
      tracer lanthanum permeates. These projections appear to overlap with each other
      in the centre of the intercellular cleft; this would provide a particularly
      flexible adaptation to maintain cell-cell contact and coordination as a
      consequence. The filamentous ribbons may be held in position by the
      intramembranous particle arrays since both have a similar size and distribution.
      These contacts are quite different from desmosomes and appear to represent a
      distinct new category of adhesive cell-cell junction. Beneath these novel
      structures, conventional pleated septate junctions are found, exhibiting the
      undulating intercellular ribbons typical of this junctional type, as well as the
      usual parallel alignments of intramembranous rows of EF grooves and PF particles.
      Below these are found gap junctions as close-packed plaques of intramembranous
      particles on either the P-face or E-face. After freeze-fracturing, the
      complementary fracture face to the particles shows pits, usually on the P-face,
      arrayed with a very precise hexagonal pattern.

PMID- 18621338
TI  - Spermatozoa of two Eledone species (Cephalopoda, Octopoda).
AB  - Spermatozoa from testes and spermatophores of two octopod species, Eledone
      cirrhosa and E. moschata, have been investigated by electron microscopy. At the
      base of the mature sperm acrosome of both species a well developed, periodic,
      conical structure is present. This structure is strikingly similar to that
      present in the Octopus sp. acrosome. Also the modalities of formation of such a
      structure during spermiogenesis show strong similarities between the Octopus and
      Eledone genera. The resistance to disruption of sperm chromatin of E. cirrhosa
      and E. moschata after treatments with SDS and mercaptoethanol which are known to
      dissolve disulfide-bridges, reveals the presence of S-S crosslinks.

PMID- 18621339
TI  - Cytochemical investigations on tunic morphogenesis in the sea peach Halocynthia
      papillosa (Tunicata, Ascidiacea). 1: demonstration of polysaccharides.
AB  - The distribution of carbohydrates was demonstrated in the embryonic, larval, and
      juvenile tunics of Halocynthia papillosa. An enzyme-gold marker
      (cellobiohydrolase-Au) was used to identify cellulose on ultrathin sections. This
      is the first time this biopolymer has been detected in the embryonic or larval
      tunic of an ascidian. Cellulose is present from the initial tail-bud stage
      onwards, as soon as the outer compartment of the tunic appears. Both compartments
      of the larval tunic also contain non-cellulosic polysaccharides, as demonstrated
      by the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method. Our
      observations point to two types of cellulose synthesis. One occurs during the
      embryonic and larval stages, when glycogen-like material is stored in epidermal
      intracellular lacunae and discharged into the tunic where it is presumably used
      to synthesize cellulose throughout the depth of the tunic. The second occurs from
      the onset of metamorphosis onwards, just above the apical plasmalemma of
      epidermal cells, like cellulose biogenesis in plants.

PMID- 18621340
TI  - Cytochemical investigations on tunic morphogenesis in the sea peach Halocynthia
      papillosa (Tunicata, Ascidiacea) 2: demonstration of proteins.
AB  - In a previous paper, cellulose fibres were demonstrated in the larval, the
      metamorphosing, and the juvenile tunics. In this paper we used cytochemical
      methods and X-ray microanalysis to obtain additional information on tunic
      morphogenesis in Halocynthia papillosa. The chemical composition of the tunic
      evolves with its structural complexity. The larval and juvenile fibres are shown
      to be structurally and chemically different. While neither proteins nor
      glycosaminoglycans seem to be associated with the larval fibres, the juvenile
      fibres consist of a cellulose core wrapped in a sheath of tannophilic proteins.
      Patches of glycosaminoglycans line their longitudinal axes. In the course of
      metamorphosis, the cuticle undergoes profound modifications in regions of spine
      morphogenesis. Granular material that was previously called fibro-granular
      material (Lubbering et al., 1993) is essential to the formation of cuticular
      plates and spines. During metamorphosis, this material accumulates in epidermal
      granules and is discharged into the tunic. It crosses the fundamental layer of
      the tunic and reaches the cuticle. Our results strongly suggest that this
      material consists of proteins rich in cysteine and hydrophobic amino acids.

PMID- 18621341
TI  - The developmental expression of serotonin-immunoreactivity in the brain of the
      pupal honeybee.
AB  - The biogenic amine serotonin is a neurotransmitter and modulator in both
      vertebrates and invertebrates. In the CNS of insects, serotonin is expressed by
      identifiable subsets of neurons. In this paper, we characterize the onset of
      expression in the brain and suboesophageal ganglion of the honeybee during pupal
      development. Several identified serotonin-immunoreactive neurons are present in
      the three neuromeres of the suboesophageal ganglion the dorsal protocerebrum, and
      the deutocerebrum at pupal ecdysis. Further immunoreactive neurons are
      incorporated into the developing pupal brain in two characteristic developmental
      phases. During the first phase, 5 days after pupal ecdysis, serotonin
      immunoreactivity is formed in the protocerebral central body, the lamina and
      lobula, and the deutocerebral antennal lobe. During the second phase, 2 days
      later, immunoreactivity appears in neurons of the protocerebral noduli of the
      central complex, the medulla, and the pedunculi and lobes of the mushroom bodies.
      Three novel serotonin-immunoreactive neurons that innervate the central complex
      and the mushroom bodies can be individually identified.

PMID- 18621342
TI  - Sensilla on the maxillary palps of Helicoverpa armigera caterpillars: in search
      of the CO(2)-receptor.
AB  - The ultrastructure of sensilla on the maxillary palps of Helicoverpa armigera
      caterpillars has been investigated in order ot find candidates for CO(2)
      receptors. The following sensilla are found on the palps: a) 8 chemosensory pegs
      at the tip; b), a large distal pore plate; c), a smaller proximal pore plate; d),
      a digitiform organ; e), a campaniform sensillum; and f), 3 scolopidia. Each
      chemosensory peg at the tip is innervated by 4-5 sensory neurons. Five of these
      pegs are most probably contact chemoreceptors, because each has a dendrite with a
      tubular body. The distal pore plate has a porous cuticle and is innervated by 3
      sensory neurons, each of which sends a highly branched dendrite into a large
      cuticular cavity. The proximal pore plate is made up from two fused organs, has
      also a porous cuticle, and is innervated by two sensory neurons which send their
      dendrites into a narrow cuticular channel. The digitiform organ is innervated by
      one sensory cell which sends a highly lamellated dendrite into a narrow channel
      within a chip-shaped protrusion of the porous cuticle. For several reasons, the
      digitiform organ is the most probable candidate for the CO(2)-receptor. Another
      possible candidate is the distal pore plate.

PMID- 18621343
TI  - Autoradiographic localization of [22,23-(3)H(2)] dihydroazadirachtin binding
      sites in desert locust testes and effects of Azadirachtin on sperm motility.
AB  - Localization of [22,23-(3)H(2)] dihydroazadirachtin binding sites in locust
      (Schistocerca gregaria) testes was investigated by in vitro autoradiography.
      Preferential binding of the ligand at concentrations of 10(-8) M was located in
      the testes follicles, localized on the tail portions of developing sperm. This
      binding was fully displaceable with an excess of unlabelled ligand. The results
      indicate that Azadirachtin binds preferentially to sites on the organelles
      associated with maturing locust sperm tails. Azadirachtin, at concentrations of
      10(-4)M and above, caused a time-dependent reduction in the motility of eupyrene
      sperm bundles liberated from the accessory glands of mature male S. gregaria. The
      effect of azadirachtin on boar sperm motility was also time- and concentration
      dependent. Forward motility was significantly reduced by concentrations above 10(
      5)M at each time interval (P<0.05).

PMID- 18621344
TI  - The digestive gland of Viviparus ater (Mollusca, Gastropoda, Prosobranchia): an
      ultrastructural and histochemical study.
AB  - The digestive gland of Viviparus ater was studied using histochemical and
      ultrastructural methods. Only one cell type was observed in the tubule epithelium
      of the gland. The cells are involved in an endocytotic process mediated by
      clathrin-coated vesicles and in the intracellular digestion of food materials
      (thus they can be regarded as digestive cells). The different stages of digestion
      and exocytotic extrusion of residual bodies into the tubule lumen were shown by
      electron microscopy. Very few, small mucocytes are scattered among the digestive
      cells. Calcium concretions, glycogen-containing cells and endocrine cells are
      scattered in the area of connective tissue present among the digestive tubules.

PMID- 18621345
TI  - Effect of Azadirachtin on vitellogenesis of Labidura riparia (Insect Dermaptera).
AB  - This study investigates the effects of the insect growth regulator Azadirachtin
      (AZA) on the ultrastructure of ovaries and fat body of the earwig Labidura
      riparia. Ovarian development is severely reduced in AZA-injected females in a
      dose-dependent manner. Follicles exhibit degenerative changes, separation of
      follicle cells from the oocyte, and lack of pinocytotic vesicles as of yolk
      spheres in cortical ooplasm. Adipocytes show fragmented rough endoplasmic
      reticulum (RER), numerous autophagic vacuoles, multivesicular bodies, osmiophilic
      lipid droplets, and many large glycogen areas. Gel electrophoresis reveals that
      vitellogenin is absent from both fat body and hemolymph, and that vitellin is not
      deposited in the ovary. These pathological effects are not linked to an absence
      of feeding. The effect of AZA on vitellogenesis is rescuable by Juvenile hormone
      (JH) treatment. The inhibition of vitellogenesis by AZA is discussed on the basis
      of its direct cytotoxic effect as well as its interference with the
      neuroendocrine system.

PMID- 18621346
TI  - A different oogenetic pattern in a US apoikogenous scorpion, Vaejovis spinigerus
      (Scorpiones, Vaejovidae).
AB  - The ovariuterus of the scorpion Vaejovis spinigerus (Scorpiones, Vaejovidae)
      differs from that of all other apoikogenic species studied so far in that the
      oocytes mature inside, rather than on the outer surface, of the ovariuterus
      tubes. Only the small, second and third oocyte generations are situated on the
      outer surface, sometimes even on top, of the mature oocytes. This oogenetic
      pattern has so far not been described in any other scorpion species. Since no
      males were found in the populations studied here, this species can be assumed to
      be parthenogenetic. However, this point needs more concrete proof.

PMID- 18621347
TI  - Isolation and comparative study of the nucleocapsids of measles and canine
      distemper viruses from infected cells.
AB  - Nucleocapsids were isolated and purified from cells infected with measles and
      canine distemper virus (CDV). Electron microscopy of negatively stained
      nucleocapsids revealed the mean outside diameter was approximately 17-18 nm in
      each case and was not significantly different from similar measurements obtained
      with SV5 nucleocapsids and tobacco mosaic virus (TMV). All nucleocapsids also
      revealed central hollow cores which ranged from 4.3 to 5.2 nm. Direct chemical
      determinations showed that both CDV and measles virus nucleocapsids contained
      about 5% RNA. UV absorption spectra of measles and CDV nucleocapsids were typical
      for nucleoproteins and 280 260 nm ratios gave estimates of 5% RNA in each case.
      Buoyant density determinations in CsCl with both unlabeled and 32P-labeled
      nucleocapsids gave figures of 1.29-1.30 g/cc. Sedimentation analysis by
      analytical and sucrose gradient centrifugation revealed considerable
      heterogeneity, with nucleocapsids ranging from about 200-300 S. This
      heterogeneity was shown by electron microscopy to be due to the highly fragmented
      nature of the nucleocapsids. Analysis of CDV and measles nucleocapsids by SDS
      polyacrylamide gel electrophoresis revealed a single major polypeptide when
      infected cells were harvested in the absence of proteolytic enzymes. These had
      estimated molecular weight of 54,000 (CDV) and 61,000 (measles). However,
      nucleocapsids prepared from cells harvested with the aid of trypsin or pronase
      contained two polypeptides (38,000 and 24,000 for measles; 27,000 and 22,500 for
      CDV), while similarly prepared SV5 nucleocapsid contained only a single
      polypeptide (44,500). These differences in polypeptide composition were
      correlated with differences in morphologic appearance of the nucleocapsids.
      Nucleocapsids harvested from cells in the absence of proteolytic enzymes had a
      loosely coiled, flexible appearance, while those harvested from cells treated
      with trypsin or pronase had a tightly coiled, rigid appearance. RNA was extracted
      from 32P-labeled measles and CDV nucleocapsids. Treatment with RNase A converted
      most of the 32P to a TCA-soluble form and DNase had no effect. Base compositions
      were determined on the 32P-labeled RNA and both viruses were rich in uracil, the
      molar ratios for the four bases were similar for each virus and were not
      significantly different from values reported in the literature for the better
      characterized members of the Paramyxovirus group (NDV, Sendai and SV5).

PMID- 18621348
TI  - Polypeptides of mammalian oncornaviruses. II. Characterization of a murine
      leukemia virus polypeptide (p15) bearing interspecies reactivity.
AB  - Polypeptide p15 from Friend leukemia virus was isolated by multiple gel
      filtration steps in guanidine hydrochloride. Because of its marked tendency to
      aggregate, renaturation of the protein was performed in the presence of 0.2%
      sodium deoxycholate. Serological analyses revealed cross reactivity with other
      mammalian C-type oncornaviruses.

PMID- 18621349
TI  - Morphogenesis of the tail of bacteriophage lambda I. In vitro intratail
      complementation.
AB  - By studying nonsense mutants in ten of the 11 known tail genes of bacteriophage
      lambda we obtained the following results. Concentrated tail(-)-lysates complement
      each other in nearly all possible (45) combinations. The efficiency of
      complementation is very dependent on physical parameters (lysis procedure,
      concentration, temperature) and on the mutants used for complementation (i.e.,
      type of precursors present, absence or presence of abortive structures, polarity
      effects of some nonsense mutants). Gene product dosage experiments, in which the
      ratio of concentrations of the different precursors present in different lysates
      is varied up to four orders of magnitude, allow us to distinguish five classes of
      intratail complementations. By these studies we detected that the morphogenetic
      action of at least two gene products, pV and pM, is extremely concentration
      dependent. Furthermore the gene product dosage experiments allow us to deduce for
      five gene products the following sequence of morphogenetic action during lambda
      tail assembly: (pJ,pM), (pV,pU), pZ. Finally, we find that our in vitro
      complementation data are consistent with already known polarity properties of
      nonsense tail(-)-mutants of phage lambda.

PMID- 18621350
TI  - Electrophoretic separation of dsRNA genome segments from Fiji disease and maize
      rough dwarf viruses.
AB  - By employing two different buffer solutions for polyacrylamide gel
      electrophoresis, all genome segments of Fiji disease and maize rough dwarf virus
      were separated. Fiji disease virus contains ten genome segments with approximate
      genome molecular weights of 19.26 x 10(6) and 19.85 x 10(6), depending on the
      buffer employed for electrophoresis. Maize rough dwarf virus possesses ten dsRNA
      segments and according to the buffer employed for electrophoresis the approximate
      molecular weights of the genome were 18.91 x 10(6) and 19.61 x 10(6). In the
      samples of maize rough dwarf virus analysed, the evidence indicates that two
      types of virions were present which were distinguished by a slight difference in
      molecular weight for segment 10. The electrophoretic patterns for all dsRNA
      components of Fiji disease and maize rough dwarf viruses were very similar
      suggesting a close relationship between them.

PMID- 18621351
TI  - Structure of herpes simplex virus DNA: topography of the molecule. I. Absence of
      circularly permuted sequences.
AB  - Only linear structures were produced by re-annealing denatured herpes simplex
      type 1 virus (HSV)-DNA molecules, while T4-DNA molecules (known to be circularly
      permuted and therefore used as controls in the parallel tests) formed circles.
      These results suggested that HSV-DNA is a nonpermuted collection of sequences.
      Unfortunately, most of the linear structures observed after re-annealing were not
      full-length duplexes, thus making this test not quite satisfactory. Therefore
      another permutation test, the central region deletion experiment, was employed.
      Its results indicated that short fragments liberated from the ends of HSV-DNA by
      enzymatic treatment contained only a portion of the sequences present in the
      complete molecules. On the other hand, the presence of apparently all sequences
      was found in the short end-fragments of the control T4-DNA. These data also
      provide evidence that HSV-DNA molecules are not formed by circularly permuted
      collections of sequencies.

PMID- 18621352
TI  - Viral RNA synthesis is renewed in protoplasts isolated from TMV-infected Xanthi
      tobacco leaves in an advanced stage of virus infection.
AB  - TMV-RNA synthesis was shown to be renewed in protoplasts isolated from TMV
      infected Xanthi tobacco leaves in which virus synthesis has already slowed down
      or stopped. This was demonstrated by the use of isotope techniques in three
      different disease situations: (a) in primarily infected leaves 8-10 days after
      infection, (b) in secondarily infected leaves 2 mo after infection, and (c) in
      stable green areas ("true dark green islands" according to the terminology of
      Atkinson and Matthews, 1970) of leaves exhibiting mosaic symptoms.

PMID- 18621353
TI  - Murine sarcoma virus defectiveness. Viral polymerase expression in murine and
      nonmurine host cells transformed by S + L - type murine sarcoma virus.
AB  - Sarcoma virus-positive, leukemia virus-negative (S + L -) mouse cells transformed
      by defective but rescuable murine sarcoma virus (MSV) release noninfectious type
      C virions with a quantitative deficiency of viral-type RNA-dependent DNA
      polymerase (RDDP). Human S + L - cells containing the same genome fail to express
      any detectable viral-type reverse transcriptase. To study this difference in MSV
      expression, second-generation MSV from the S + L - human cells is recloned in
      dog, mink, and back into mouse cells. Heterologous host dog and mink S + L - cell
      clones, like human S + L - cell clones, fail to release viral-type reverse
      transcriptase into culture supernatant fractions. All second-generation
      homologous mouse S + L - cell clones again release viral reverse transcriptase in
      supernatant fractions, indicating that the MSV genome has not been altered in
      this function. Using (dT)(12-18)-cellulose and phosphocellulose chromatography of
      cellular polymerase preparations, no intracellular buildup of unreleased murine
      reverse transcriptase is detected in the S + L - clones. The data presented here
      suggest that the MSV genome is defective in the information for the viral core
      protein RDDP. The implications of these findings for the genetic study of MSV are
      discussed.

PMID- 18621354
TI  - A gene of bacteriophage T4 controlling the modification of host valyl-tRNA
      synthetase.
AB  - Two hydroxylamine-induced mutants of bacteriophage T4 defective in modification
      of host valyl-tRNA synthetase have been isolated by assay of crude extracts for
      the activity that is characteristic of the wild-type virus. The mutations define
      a single gene that is situated between the rI and e genes on the T4 genetic map.
      This new gene is designated vs for valyl-tRNA synthetase. One of the mutations
      may be of the missense type since it results in the production of a valyl-tRNA
      synthetase activity that has unusual urea-inactivation properties. The other
      appears to be an amber mutation since the viral enzyme can only be found after
      infection of cells that are permissive for amber mutations. No differences in
      growth properties were found between wild type and amber mutant strains on the
      nonpermissive host. We conclude that the bacteriophage T4 valyl-tRNA synthetase
      is not essential for viability under prevailing laboratory conditions.

PMID- 18621355
TI  - The smallest protein of Sendai virus: its candidate function of binding
      nucleocapsid to envelope.
AB  - The smallest nonglycosylated protein, VP5 (MW, 35,000), of Sendai virus was
      investigated for its location and function. Virion-associated VP5 resisted
      digestion by trypsin, fungal semi-alkali protease, or chymotrypsin, suggesting
      that VP5 is not an external protein. A close association of VP5 with both
      envelope and nucleocapsid was first established by polypeptide analyses and
      electron microscopic examinations of fractions obtained by a rate zonal
      centrifugation of alkali-Tween 20-treated virions. Second, by CsCl equilibrium
      centrifugation of the same alkali-Tween 20-disrupted virions, nucleocapsids free
      of VP5 (rho = 1.323) and those associated with VP5 (rho = 1.297) were separated.
      The former had a width of 18 nm, but the latter, a broad width ranging from 18 to
      40 nm (mean, 30 nm). Third, Triton X-100 treatment of the virions without KCl
      left VP5 in association with nucleocapsid, and, by electron microscopy, globular
      structures consisting of folded nucleocapsid were seen, while the same treatment
      with 1 M KCl completely removed VP5 from nucleocapsid and straightened
      nucleocapsids were observed. These three results suggest that VP5 bound to
      nucleocapsid is functioning to associate it to envelope and to sustain the
      spherical shape of the virion.

PMID- 18621356
TI  - Polyacrylamide disc electrophoresis of the soluble leaf proteins from Nicotiana
      tabacum var. 'Samsun' and 'Samsun NN'. IV. Similarity of qualitative changes of
      specific proteins after infection with different viruses and their relationship
      to acquired resistance.
AB  - The development of systemic mosaic symptoms on Nicotiana tabacum var. 'Samsun' or
      'Samsun NN' after infection with potato virus X (PVX), potato virus Yo (PVYo) or
      cucumber mosaic virus (CMV) was accompanied by differing alterations in protein
      constitution upon electrophoresis in polyacrylamide gels. Small amounts of four
      new protein components I-IV, identical to those found earlier in tobacco mosaic
      virus (TMV) infected Samsun NN, were observed in both varieties after infection
      with CMV. Only bands I and II were present after infection with PVYo, whereas no
      new components were detected in plants infected with PVX. Symptom expression
      differed in CMV-infected Samsun and Samsun NN, but changes in protein
      constitution were essentially similar for the two varieties. The induction of
      localized or systemic necrosis with tobacco necrosis virus, tobacco rattle virus
      or potato virus Yo always led to similar alterations and the appearance of the
      four new protein components in both varieties. Bands I-IV also occurred in
      symptomless leaves that developed after inoculation. However, the relative
      proportions of the bands varied with the variety used and with the characteristic
      of the infecting virus to remain localized or become systemic. In the variety
      Samsun NN, the presence of the new protein components closely correlated with the
      expression of acquired resistance after challenge inoculation with TMV. Systemic
      acquired resistance was also expressed in plants sprayed with mercuric chloride,
      although no new components had been induced. Inoculation with yeast-RNA induced
      only localized resistance by a mechanism that seems to differ from that of
      systemic acquired resistance and does not involve new protein components. In
      detached leaves of TMV-infected Samsun NN, lesions enlarged to a greater extent,
      and new protein components I-IV were induced to lower levels than in attached
      leaves. These observations are consistent with a role of the new protein
      components in limiting virus multiplication or spread.

PMID- 18621357
TI  - "Oryctes" virus replication: Electron microscopic observations on infected moth
      and mosquito cells.
AB  - "Oryctes" virus replicates efficiently in continuous moth (Spodoptera frugiperda)
      and mosquito (Aedes albopictus) cell cultures. Progeny virus was detected by
      bioassay and electron microscopy 15 hr after infection in both cell cultures. S.
      frugiperda cells permitted replication morphologically similar to that observed
      in vivo occurring in the cell nucleus. A. albopictus cells permitted replication
      of the virus solely in the cytoplasm.

PMID- 18621358
TI  - Superior oblique palsy with class III tendon anomaly.
AB  - PURPOSE: To describe the clinical findings and surgical results of superior
      oblique palsy with class III tendon anomaly. DESIGN: Observational case series.
      METHODS: One hundred and forty-one cases of congenital and idiopathic superior
      oblique palsy were operated on by one surgeon (M.S.) between September 1, 1995
      and August 31, 2007. The superior oblique tendons were explored in 26 cases.
      Among these, five cases were found to have the distal end of the tendon inserted
      into the Tenon capsule. Preoperative eye alignment, visual acuity, stereopsis
      measured with Titmus stereo acuity tests (Stereo Fly SO-001; Stereo Optical Co,
      Chicago, Illinois, USA), and magnetic resonance imaging findings were collected
      from the patients' records. Main outcome measures included preoperative eye
      position, surgical results, and stereoscopic acuity. Stereopsis and the amount of
      vertical deviation were compared in cases with class I, II, and IV tendon
      anomalies. RESULTS: A total of eight surgeries were performed on five patients
      with class III superior oblique tendon anomaly. Three muscles were operated on
      for each patient. The amount of vertical deviation was not significantly
      different from other types of tendon anomaly. Patients with class I to III tendon
      anomalies obtained good stereopsis after strabismus surgery, whereas cases with
      class IV anomaly achieved only limited stereopsis. The number of surgeries
      performed was significantly higher in cases with class IV anomaly. CONCLUSIONS:
      Without careful search of the Tenon capsule, the condition can be misdiagnosed as
      an absent tendon. Strengthening the superior oblique tendon in the Tenon capsule
      can improve the alignment significantly.

PMID- 18621360
TI  - Mast cells populations fluctuate along the spinal dura mater of the developing
      rat.
AB  - The present study reveals developmental changes in the number, the phenotype and
      the distribution pattern of mast cells (MCs) along the cervical, the thoracic and
      the lumbar parts of the spinal dura mater. Postnatal infiltration of spinal dura
      by MCs does not appear to follow a sequential developmental pattern and meningeal
      MCs are unevenly distributed along the various parts of the examined dura. At
      each spinal level, areas most densely populated by MCs are the dorsal dura and
      the dural sleeves of the dorsal (sensory) spinal roots The developmental time
      course of the total MCs number is characterized by significant fluctuations in
      all three parts examined, with notable increases at P1, P4, P21 and P60 (peak
      value) for the cervical part, at P1 (peak value), P7 and P21 for the thoracic
      part and at P1, P7 (peak value) and P30 for the lumbar part. At P180, MCs number
      declines to 56%, 33% and 13% of the peak values for the cervical, the thoracic
      and the lumbar part, respectively. However, a different developmental pattern is
      followed by each subpopulation of MCs identified on the basis of their staining
      characteristics, namely connective tissue type mast cells (CTMCs), mucosal type
      or cells with characteristics of immature mast cells (MTMCs) and mixed type MCs,
      in each part examined. The findings may be of importance in elucidating
      physiological and pathological processes in the dura mater and the vertebral
      column.

PMID- 18621359
TI  - Fusiform function in children with an autism spectrum disorder is a matter of
      "who".
AB  - BACKGROUND: Despite the importance of face processing for normal social
      development, no functional magnetic resonance imaging studies of face processing
      in autism have focused exclusively on the childhood years. To fill this gap, 45
      children aged 6-12 participated in practice scans. After exclusion due to motion,
      11 children with an ASD and 11 age-matched normal control subjects were included
      in final analyses. METHODS: Stimuli consisted of pictures of a familiar adult,
      familiar child, stranger adult, stranger child, and objects. During the scan,
      children pressed a button in response to an identical face shown on two
      consecutive trials. On the basis of our prior research, masks of four anatomic
      regions of interest (ROIs) including the fusiform gyrus, amygdala, and anterior
      and posterior cingulate were created for each subject and manually edited for
      anatomic precision. Following deconvolution analyses, the number of voxels
      significantly active and percent signal change values that fell within each ROI
      mask were calculated for each subject. RESULTS: Analyses revealed normal fusiform
      activity in children with autism when viewing a face of their mother or other
      children. In contrast, looking at stranger adult faces initiated profound
      deficits in that the mean number of significantly active voxels in the fusiform
      bilaterally was approximately 25% of that shown in typically developing children.
      CONCLUSIONS: A selective fusiform deficit in response only to the faces of adult
      strangers may be the result of reduced attention and interest during those
      conditions. Face processing abnormalities found in autism beyond the fusiform
      likely exist.

PMID- 18621361
TI  - Number words in young children's conceptual and procedural knowledge of addition,
      subtraction and inversion.
AB  - Three studies addressed children's arithmetic. First, 50 3- to 5-year-olds judged
      physical demonstrations of addition, subtraction and inversion, with and without
      number words. Second, 20 3- to 4-year-olds made equivalence judgments of
      additions and subtractions. Third, 60 4- to 6-year-olds solved addition,
      subtraction and inversion problems that varied according to the inclusion of
      concrete referents and number words. The results indicate that number words play
      a different role in conceptual and procedural development. Children have strong
      addition and subtraction concepts before they can translate the physical effects
      of these operations into number words. However, using number words does not
      detract from their calculation procedures. Moreover, consistent with iterative
      relations between conceptual and procedural development, the results suggest that
      inversion acquisition depends on children's calculation procedures and that
      inversion understanding influences these procedures.

PMID- 18621362
TI  - Implementation of CAM physiotherapy device with a virtual spring.
AB  - Continuous passive motion (CPM) and continuous active motion (CAM) physiotherapy
      devices are commonly used to promote rehabilitation of damaged synovial joints. A
      CPM/CAM device with no resistive CAM-type components is presented. In the CPM
      mode the electric motor functions conventionally, but in the CAM mode,
      intelligent use of the motor simulates resistive components by driving the motor
      to exert a force opposing the patient's muscle activity, so as to simulate the
      effect of a spring load. The system easily connects to the Internet or other data
      links for automatic monitoring of home patients, hospital networks, research
      stations, or telemedicine applications.

PMID- 18621363
TI  - The body unbound: vestibular-motor hallucinations and out-of-body experiences.
AB  - Among the varied hallucinations associated with sleep paralysis (SP), out-of-body
      experiences (OBEs) and vestibular-motor (V-M) sensations represent a distinct
      factor. Recent studies of direct stimulation of vestibular cortex report a
      virtually identical set of bodily-self hallucinations. Both programs of research
      agree on numerous details of OBEs and V-M experiences and suggest similar
      hypotheses concerning their association. In the present study, self-report data
      from two on-line surveys of SP-related experiences were employed to assess
      hypotheses concerning the causal structure of relations among V-M experiences and
      OBEs during SP episodes. The results complement neurophysiological evidence and
      are consistent with the hypothesis that OBEs represent a breakdown in the normal
      binding of bodily-self sensations and suggest that out-of-body feelings (OBFs)
      are consequences of anomalous V-M experiences and precursors to a particular form
      of autoscopic experience, out-of-body autoscopy (OBA). An additional finding was
      that vestibular and motor experiences make relatively independent contributions
      to OBE variance. Although OBEs are superficially consistent with universal
      dualistic and supernatural intuitions about the nature of the soul and its
      relation to the body, recent research increasingly offers plausible alternative
      naturalistic explanations of the relevant phenomenology.

PMID- 18621364
TI  - "Do you remember what you did on March 13, 1985?" A case study of confabulatory
      hypermnesia.
AB  - We report on a patient, LM, with a Korsakoff's syndrome who showed the unusual
      tendency to consistently provide a confabulatory answer to episodic memory
      questions for which the predicted and most frequently observed response in normal
      subjects and in confabulators is "I don't know". LM's pattern of confabulation,
      which we refer to as confabulatory hypermnesia, cannot be traced back to any more
      basic and specific cognitive deficit and is not associated with any particularly
      unusual pattern of brain damage. Making reference to the Memory, Consciousness
      and Temporality Theory - MCTT (Dalla Barba, 2002), we propose that LM shows an
      expanded Temporal Consciousness - TC, which overflows the limits of time ("Do you
      remember what you did on March 13, 1985?") and of details ("Do you remember what
      you were wearing on the first day of summer in 1979?") that are usually respected
      in normal subjects and in confabulating patients.

PMID- 18621365
TI  - The incidence and determinants of visual phenomenology during out-of-body
      experiences.
AB  - The visual content of out-of-body experiences (OBEs) has received little
      attention but a number of theories of OBEs include implicit predictions regarding
      the determinants of this phenomenological feature. Hypnagogic imagery and unusual
      sleep experiences, weak synaesthesia and preference for employing object and
      spatial visual imagic cognitive styles were psychometrically measured along with
      the incidence of self-reported OBEs and the absence or presence of visual content
      therein, in a sample of individuals drawn from the general population. Seventy
      percent of individuals who had experienced an OBE reported that the experience
      included some form of visual content. These individuals exhibited greater scores
      on the measures of preference for object visual imagic cognition and weak
      synaesthesia than those who reported an absence of visual content during their
      OBE. Subsequent analysis revealed that the measure of weak synaesthesia was the
      stronger discriminator of the two cohorts. The results are discussed within the
      context of the synaesthetic model of visual phenomenology during OBEs (Brugger,
      2000; Irwin, 2000). This account proposes that visual content appears during
      these experiences through a process of cognitive dedifferentiation in which
      visual hallucinations are derived from available non-visual sensory cues and that
      such dedifferentiation is made possible through an underlying characteristic
      hyperconnectivity of cortical structures regulating vestibular and visual
      representations of the body and those responsible for the rotation of
      environmental objects. Predictions derived from this account and suggestions for
      future research are proffered.

PMID- 18621366
TI  - Ganzfeld-induced hallucinatory experience, its phenomenology and cerebral
      electrophysiology.
AB  - Ganzfeld, i.e., exposure to an unstructured, uniform stimulation field, elicits
      in most observers pseudo-hallucinatory percepts, and may even induce global
      functional state changes ('altered states of consciousness'). The present paper
      gives a comprehensive overview of the phenomenology of subjective experience in
      the ganzfeld and its electrophysiological correlates. Laboratory techniques for
      visual or multi-modal ganzfeld induction are explained. The spectrum of ganzfeld
      induced phenomena, ranging from elementary percepts to complex, vivid, dream-like
      imagery is described, and the latter illustrated by transcripts of subjects'
      reports. Similarities and differences to related sensory/perceptual phenomena are
      also discussed. Earlier findings on electrophysiological correlates of the
      ganzfeld are reviewed. Our own studies of electroencephalographic (EEG) activity
      in the ganzfeld are presented in some detail, and a re-analysis of data on EEG
      correlates of hallucinatory percepts in statu nascendi is reported. The results
      do not support the hypothesis of the hypnagogic origin of the percepts; the
      ganzfeld-induced steady-state is an activated state, and the spectral EEG
      dynamics in the alpha frequency range reveals processes of attention shifts and
      percept formation. The final section is devoted to the controversial topic of
      allegedly anomalous communication between human subjects ('ganzfeld telepathy').
      It is shown that the use of ganzfeld in this research field relies partly on
      unsupported hypotheses concerning ganzfeld-induced states, partly on a weak
      conceptual background of the experimental procedure. The role of a particular
      belief system shared by the participants and experimenters is critically
      discussed.

PMID- 18621367
TI  - Beyond body experiences: phantom limbs, pain and the locus of sensation.
AB  - Reports of perceptual experiences are found throughout history. However, the
      phenomena considered worthy of note have not been those that nurture our survival
      (the veridical features of perception) but the oddities or departures from the
      common and commonplace accuracies of perception. Some oddities (like afterimages)
      could be experienced by everyone, whereas others were idiosyncratic. Such
      phenomena were often given a paranormal interpretation before they were absorbed
      into the normal science of the day. This sequence is examined historically in the
      context of beyond body experiences or phantom limbs. The experience of sensations
      in lost body parts provides an example of the ways in which novel phenomena can
      be interpreted. The first phase of description probably occurred in medieval
      texts and was often associated with accounts of miraculous reconnection. Ambroise
      Pare (1510-1590) initiated medical interest in this intriguing aspect of
      perception, partly because more of his patients survived the trauma of surgery.
      Description is followed by attempts to incorporate the phenomenon into the body
      of extant theory. Rene Descartes (1596-1650) integrated sensations in amputated
      limbs into his dualist theory of mind, and used the phenomenon to support the
      unity of the mind in comparison to the fragmented nature of bodily sensations.
      Others, like William Porterfield (ca. 1696-1771), did not consider the phenomenon
      as illusory and interpreted it in terms of other projective features of
      perception. Finally, the phenomenon is accepted and utilized to gain more
      insights into the functioning of the senses and the brain. The principal features
      of phantom limbs were well known before they were given that name in the 19th
      century. Despite the puzzles they still pose, these phantoms continue to provide
      perception with some potent concepts: the association with theories of pain has
      loosened the link with peripheral stimulation and emphasis on the phenomenal
      dimension has slackened the grip of stimulus-based theories of perception. The
      pattern of development in theories of phantom limbs might provide a model for
      examining out-of-body experiences (OBEs).

PMID- 18621369
TI  - The role of integrin alpha D beta2 (CD11d/CD18) in monocyte/macrophage migration.
AB  - Integrin alpha(D)beta(2) (CD11d/CD18) is a multiligand macrophage receptor with
      recognition specificity identical to that of the major myeloid cell-specific
      integrin alpha(M)beta(2) (CD11b/CD18, Mac-1). Despite its prominent upregulation
      on inflammatory macrophages, the role of alpha(D)beta(2) in monocyte and
      macrophage migration is unknown. In this study, we have generated model and
      natural cell lines expressing different densities of alpha(D)beta(2) and examined
      their migration to various extracellular matrix proteins. When expressed at a low
      density, alpha(D)beta(2) on the surface of recombinant HEK293 cells and murine IC
      21 macrophages cooperates with beta(1)/beta(3) integrins to support cell
      migration. However, its increased expression on the alpha(D)beta(2)-expressing
      HEK293 cells and its upregulation by PMA on the IC-21 macrophages result in
      increased cell adhesiveness and inhibition of cell migration. Furthermore,
      ligation of alpha(D)beta(2) with anti-alpha(D) blocking antibodies restores
      beta(1)/beta(3)-driven cell migration by removing the excess alpha(D)beta(2)
      mediated adhesive bonds. Consistent with in vitro data, increased numbers of
      inflammatory macrophages were recovered from the inflamed peritoneum of mice
      after the administration of anti-alpha(D) antibody. These results demonstrate
      that the density of alpha(D)beta(2) is critically involved in modulating
      macrophage adhesiveness and their migration, and suggest that low levels of
      alpha(D)beta(2) contribute to monocyte migration while alpha(D)beta(2)
      upregulation on differentiated macrophages may facilitate their retention at
      sites of inflammation.

PMID- 18621372
TI  - REMOVED: Comparing the reproducibility of intima-media thickness measurements
      using spectral analysis.
AB  - This article has been removed, consistent with Elsevier Policy on Article
      Withdrawal. Please see http://www.elsevier.com/locate/withdrawalpolicy. The
      Publisher apologizes for any inconvenience this may cause.

PMID- 18621368
TI  - Inositol 1,4,5-trisphosphate receptor 1, a widespread Ca2+ channel, is a novel
      substrate of polo-like kinase 1 in eggs.
AB  - To initiate embryo development, the sperm induces in the egg release of
      intracellular calcium ([Ca2+](i)). During oocyte maturation, the inositol 1,4,5
      trisphosphate receptor (IP(3)R1), the channel implicated, undergoes modifications
      that enhance its function. We found that IP(3)R1 becomes phosphorylated during
      maturation at an MPM-2 epitope and that this persists until the fertilization
      associated [Ca2+](i) responses cease. We also reported that maturation without
      ERK activity diminishes IP(3)R1 MPM-2 reactivity and [Ca2+](i) responses. Here,
      we show that IP(3)R1 is a novel target for Polo-like kinase1 (Plk1), a conserved
      M-phase kinase, which phosphorylates it at an MPM-2 epitope. Plk1 and IP(3)R1
      interact in an M-phase preferential manner, and they exhibit close co
      localization in the spindle/spindle poles area. This co-localization is reduced
      in the absence of ERK activity, as the ERK pathway regulates spindle organization
      and IP(3)R1 cortical re-distribution. We propose that IP(3)R1 phosphorylation by
      Plk1, and possibly by other M-phase kinases, underlies the delivery of spatially
      and temporally regulated [Ca2+](i) signals during meiosis/mitosis and
      cytokinesis.

PMID- 18621370
TI  - Closed reduction and iliosacral percutaneous fixation of unstable pelvic ring
      fractures.
AB  - OBJECTIVE: To report clinical results of patients treated with closed reduction
      and percutaneous iliosacral screw fixation for unstable pelvic ring fractures.
      MATERIALS AND METHODS: Retrospective study using medical records, images and late
      clinical assessment of all patients treated in our centre with percutaneous
      iliosacral screw fixation for unstable pelvic ring fractures, with a minimum
      follow-up of 12 months. Seventy-three patients with a mean age of 40.3 years old
      (range 14-70 years) were treated between July 1998 and December 2005. Seventy-one
      patients were included. Fractures types included 10 AO type B and 61 AO type C
      injuries. Forty-two patients had associated injuries. Mean follow-up was 31
      months (12-96). Functional status was assessed using Majeed's grading score for
      pelvic fractures at final follow-up. RESULTS: Sixty-nine patients obtained a
      satisfactory initial reduction. Two patients had transitory postoperative
      neurological deficit. Five patients presented hardware failure. Fifteen patients
      developed sacroiliac osteoarthritis during follow-up. Good and excellent
      functional results were observed in 66 patients at final follow-up. Five patients
      had bad results, one due to infection of an anterior pelvic plate and the others
      due to painful refractory sacroiliac osteoarthritis that required a sacroiliac
      fusion. Sixty-one (86%) patients were able to return to pre-injury occupation.
      CONCLUSIONS: Good clinical results with a low and predictable rate of
      complications can be expected using closed reduction and percutaneous iliosacral
      screw fixation for unstable pelvic ring fractures.

PMID- 18621374
TI  - Intima-media thickness is a useful marker of the extent of coronary artery
      disease in patients with impaired renal function.
AB  - OBJECTIVE: The aim of the study was the assessment of intima-media thickness
      (IMT) in peripheral arteries (the carotid and the femoral artery) and its
      correlation with the extent of coronary artery disease (CAD). The second task was
      the analysis of the renal function's influence within IMT complex. METHODS: 231
      patients (men, mean age 52.8), who had undergone coronary angiography due to
      symptoms of CAD were enrolled. The ultrasound measurement of IMT in the common
      carotid artery (CCA), carotid bulb and common femoral artery (CFA) was performed.
      The relationship between IMT, renal function and the extent of CAD was evaluated.
      RESULTS: Significantly higher values of IMT in the peripheral arteries were
      observed in patients with CAD than in those without (CCA-0.91 vs 0.61 mm, carotid
      bulb-1.31 vs 0.67, CFA-1.38 vs 0.63 respectively, p<0.0001). The GFR values in
      the CAD patients significantly negatively correlated with IMT complex in CCA
      (p<0.001) and carotid bulb (p<0.05). Lower values of GFR in patients with three
      vessel disease were observed than in those patients with one- or two-vessel
      disease (p<0.05). In multifactoral analysis (post-hoc NIR test) we found that
      glomerular filtration rate (GFR) is strongly determined by age (p<0.0001), BMI
      (p<0.0001), value of carotid intima-media thickness (p<0.001), value of IMT in
      the carotid bulb (p<0.02) and the treatment with ACE-I (p<0.05). In multifactoral
      analysis we did not find any statistical influence of lipid profile and glucose
      disturbances on GFR. CONCLUSIONS: Higher peripheral artery IMTs in patients with
      CAD than in those without and patients with three-vessel disease indicate that
      IMT may be used as an early marker of atherosclerosis and reflect the severity of
      CAD. A significant negative correlation between the value of a GFR and the IMT
      confirmed the usefulness of this noninvasive method for the estimation of
      preclinical stages of atherosclerotic changes' development in patients with
      impaired renal function.

PMID- 18621373
TI  - C-reactive protein stimulates superoxide anion release and tissue factor activity
      in vivo.
AB  - C-reactive protein (CRP), the prototypic marker of inflammation, is a
      cardiovascular risk marker and recent in vitro studies suggest that it may
      promote atherogenesis. CRP promotes oxidative stress in vitro and induces tissue
      factor (TF) release. However, there is a paucity of data examining the effects of
      CRP on oxidative stress and tissue factor procoagulant activity (PCA) in vivo.
      Thus, we tested the effects of CRP administration on superoxide anion release and
      tissue factor activity and examined mechanistic pathways using a rat sterile air
      pouch model. Intraperitoneal administration of CRP (20mg/kg body weight) compared
      to human serum albumin (HuSA) increased superoxide anion release and tissue
      factor activity from peritoneal macrophages in vivo (p<0.01). This was confirmed
      using intrapouch administration of CRP (25mug/mL) compared to HuSA. Pretreatment
      with reactive oxygen species (ROS) scavengers or protein kinase C (PKC) inhibitor
      significantly abrogated CRP-induced superoxide anion release and tissue factor
      activity. Pretreatment with extracellular signal-regulated kinase (ERK) and Jun N
      terminal kinase (JNK) inhibitors, but not p38 mitogen-activated protein kinase
      (p38MAPK) significantly decreased CRP-induced superoxide anion release from
      macrophages in vivo. CRP-induced tissue factor activity in vivo was abrogated by
      pretreatment with inhibitors to p38MAPK, JNK and NFkappab (nuclear factor
      kappab), but not ERK. Antibodies to Fc gamma receptors, CD32 and CD64 resulted in
      significant reduction in CRP-induced superoxide and tissue factor activity in
      vivo. Thus, CRP appears to induce oxidative stress in vivo by stimulating NADPH
      oxidase via PKC, ERK and JNK phosphorylation, and induces tissue factor PCA in
      vivo via upregulation of PKC, p38MAPK, JNK, ROS and NFkappab. CRP-induced ROS
      appears to precede tissue factor release. These effects are abrogated by blocking
      Fc gamma receptors, CD32 and CD64. This in vivo demonstration provides further
      evidence for a role for CRP in atherothrombosis.

PMID- 18621375
TI  - A method to obtain surface strains of soft tissues using a laser scanning device.
AB  - A three-dimensional laser scanning device was developed allowing surface
      digitization of musculoskeletal and soft tissue structures under different loads.
      Image-processing algorithms were formulated for image registration. These were
      used to determine displacement mapping and then surface strains. Various
      validation experiments were performed. Accuracy was obtained on a test cylinder
      after rigid rotation and on a silicon cylinder compressed in four loading steps.
      The system accuracy (including the scanning and the data evaluation) was +/-0.10%
      strain in vertical and +/-0.16% strain in shear and circumferential direction for
      the rigid rotation exhibiting the zero-strain situation. Silicon cylinder
      compression showed that the accuracy was best for small strains, whereas strains
      >5% evoked a slight underestimation increasing further with higher strains (error
      of 0.54% for 7.22% vertical strain). It was possible to increase the accuracy by
      performing the strain measurements via sub-steps. This had a remaining error of
      0.41% for 7.22% vertical strain. A further experiment was carried out in order to
      acquire the surface strain of a human lumbar intervertebral disc while it was
      forced to flexion and extension. This study introduced a laser-based scanning
      method to obtain soft tissue surface strains. It is important to know the strain
      distribution of musculoskeletal structures and soft tissues. This could help to
      better understand the mechanical loading of biological structures e.g. the
      processes in fracture healing. These data could also be used to assist in the
      validation process for finite-element models.

PMID- 18621376
TI  - Effects of suppressing arm swing on kinematics, kinetics, and energetics of human
      walking.
AB  - Human walking is characterized by pronounced arm movement, yet computer
      simulation models of walking usually lump the mass of the arms with the head and
      torso. The implications of this simplification have not been thoroughly
      documented in the literature. Thus, the purpose of this study was to establish
      the dependence of several biomechanical and energetic variables on suppressing
      arm swing (AS) in walking. Eight healthy adult subjects walked with and without
      normal AS, with speed and stride frequency/length matched between trials.
      Metabolic data were collected during walking on a treadmill, while kinematic and
      kinetic data were collected during overground walking. Gross and net energy
      expenditure were significantly higher during walking without AS, with the mean
      differences being less than 10%. Joint angles, angular velocities, and ground
      reaction forces were nearly identical for walking with and without AS. Most joint
      moments and powers were also similar between AS conditions; however, some kinetic
      variables (e.g., knee joint power) exhibited larger differences, primarily during
      the stance phase. The variable that differed most between walking with and
      without AS was the free vertical moment between the foot and ground. In summary,
      most variables differed by less than 10% and were highly correlated (r0.90)
      between walking with and without normal AS. Thus, researchers may be justified in
      using walking models without articulated arms. However, a few variables exhibited
      larger differences, which might be of relevance based on the specific research
      question being addressed.

PMID- 18621377
TI  - Unusual transduction response of progenitor-derived and mature endothelial cells
      exposed to laminar pulsatile shear stress.
AB  - Progenitor-derived endothelial cells (PDECs) isolated from human umbilical cord
      blood generate a great hope in the fields of vascular tissue engineering.
      Endothelial cells subjected to shear stress convert mechanical stimuli into
      intracellular signals that affect cellular functions. It is essential to ensure
      that PDECs are able to sense shear stress as mature endothelial cells from human
      saphenous veins (HSVECs) do with mitogen-activated protein (MAP) kinase and
      nuclear factor (NF)-kappaB signal transduction pathways. HSVECs and PDECs were
      seeded on glass slides coated with gelatin and exposed to 12 dyn/cm2 in a
      parallel-plate flow chamber. In both cell types, shear stress activated
      extracellular signal-related kinase (ERK)1/2 with a rapid time course (maximum 5
      min) followed by a reduced phosphorylation, and p38 pathway. c-Jun N-terminal
      protein kinase (JNK) phosphorylation is observed only in PDECs. With respect to
      NF-kappaB translocation to the nucleus, the NF-kappaB pathway is not activated by
      flow in HSVECs and PDECs although interleukin-1alpha (IL-1alpha) activates this
      pathway in both cell types. In our experimental conditions, shear stress does not
      modify the nuclear translocation of NF-kappaB in HSVECs after IL-1alpha
      stimulation. It can be stated that PDECs are shear stress sensitive and capable
      of signal transduction as mature HSVECs are, despite the unusual transduction
      response of both cell types.

PMID- 18621378
TI  - Direct determination of the estrogenic compounds 8-prenylnaringenin, zearalenone,
      alpha- and beta-zearalenol in beer by liquid chromatography-mass spectrometry.
AB  - A novel LC-ESI-MS method for the simultaneous determination of four of the most
      significant estrogenic compounds naturally occurring in beer, 8-prenylnaringenin
      (8-PN), zearalenone (ZON), alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta
      ZOL) which requires minimal sample preparation was developed using a chemometric
      approach. Experimental design was applied to assess the effects of the LC-ESI-MS
      parameters (mobile phase flow rate, drying gas flow, nebuliser pressure and
      capillary potential) on the obtained signal and to optimize the values in order
      to provide maximum sensitivity and detectability. The proposed method is simple,
      consisting only of degassing the beer and diluting with water (1:1, v/v) before
      injection. Comparison between the two internal standards used, zearalanone (ZAN)
      and 4,2'-dihydroxychalcone (4,2'-DHC), showed that ZAN performs better as
      internal standard not only for the mycotoxins but for 8-PN as well, giving lower
      % RSDs. Under inter-day conditions mean recoveries were 107% for ZON, 87.8% for
      alpha-ZOL, 72.8% for beta-ZOL, and 77.5% for 8-PN. The corresponding % RSDs
      ranged between 5.0 and 8.0. The method limits of detection were 1.3, 1.4, 1.0 and
      0.8 ng mL(-1) for ZON, alpha-ZOL, beta-ZOL and 8-PN, respectively. The method was
      applied to 15 beer samples obtained from local supermarkets and the concentration
      of the phytoestrogen 8-PN in beer ranged between <0.8 and 38.6 ng mL(-1), while
      neither ZON nor its metabolites, alpha-ZOL and beta-ZOL, were detected.

PMID- 18621379
TI  - Improved analysis of melamine-formaldehyde resins by capillary zone
      electrophoresis-mass spectrometry using ion-trap and quadrupole-time-of-flight
      mass spectrometers.
AB  - An improved method based on capillary zone electrophoresis (CZE) coupled to
      either ion-trap (IT) mass spectrometry (MS) or quadrupole-time-of-flight (Q-TOF)
      MS for the analysis of melamine-formaldehyde condensates is presented. Employing
      a formic acid-based electrolyte containing 50% acetonitrile (ACN) and MS
      detection up to 13 compounds could be determined in lab-made resins, synthesized
      by mixing formaldehyde and melamine in different ratios ranging from 1:1.5 to
      1:4. The use of a Q-TOF-MS for detection allowed the assignment of molecular
      formulas for all 13 substances with high accuracy.

PMID- 18621380
TI  - Superhydrophobic surface from Cu-Zn alloy by one step O2 concentration dependent
      etching.
AB  - The article reports on a very simple method to fabricate superhydrophobic
      surfaces with Cu-Zn alloy via changing the local oxygen concentration and
      formation of oxygen difference cell, which can be readily realized by covering or
      contacting the Cu-Zn alloy surface with a glass slide. This superhydrophobic film
      comes from the formation of a flower-like hierarchical structure due to the
      accelerated alloy etching. In contrast, the white film grown in the un-covered
      area showed a much lower hydrophobicity due to its different morphology. These
      superhydrophobic surfaces or superhydrophobic-hydrophobic surfaces are expected
      to find applications in making self-cleaning alloy surface, in metal
      anticorrosion, and in biomineralization, etc.

PMID- 18621381
TI  - Binding energies for alkane molecules on a carbon surface from gas-solid
      chromatography and molecular mechanics.
AB  - Gas-solid chromatography was used to determine B(2s) (gas-solid virial
      coefficient) values for 12 alkanes (10 branched and 2 cyclic) interacting with a
      carbon powder (Carbopack B, Supelco). B(2s) values were determined by multiple
      size variant injections within the temperature range of 393 to 623 K with each
      alkane measured at 5 or 6 different temperatures. The temperature variations of
      the gas-solid virial coefficients were used to find the experimental adsorption
      energy or binding energy values (E( *)) for each alkane. A molecular mechanics
      based, rough-surface model was used to calculate the molecule-surface binding
      energy (E(cal)( *)) using augmented MM2 parameters. The surface model consisted
      of three parallel graphene layers with each layer containing 127 interconnected
      benzene rings and two separated nanostructures each containing 17 benzene rings
      arranged in a linear strip. As the parallel nanostructures are moved closer
      together, the surface roughness increases and molecule-surface interactions are
      enhanced. A comparison of the experimental and calculated binding energies showed
      excellent agreement with an average difference of 3.8%. Linear regressions of E(
      *) versus E(cal)( *) for the current data set and a combined current and prior
      alkane data set both gave excellent correlations. For the combined data set with
      18 linear, branched and cyclic alkanes; a linear regression of E(
      *)=0.9848E(cal)( *) and r(2)=0.976 was obtained. The results indicate that alkane
      surface binding energies may be calculated from MM2 parameters for some gas-solid
      systems.

PMID- 18621382
TI  - Goethite surface reactivity: a macroscopic investigation unifying proton,
      chromate, carbonate, and lead(II) adsorption.
AB  - The goethite surface structure has been extensively studied, but no convincing
      quantitative description of its highly variable surface reactivity as inversely
      related to its specific surface area (SSA) has been found. The present study adds
      experimental evidence and provides a unified macroscopic explanation to this
      anomalous behavior from differences in average adsorption capacities, and not in
      average adsorption affinities. We investigated the chromate anion and lead(II)
      cation adsorption behavior onto three different goethites with SSA varying from
      50 to 94 m(2)/g, and analyzed an extensive set of published anion adsorption and
      proton charging data for variable SSA goethites. Maximum chromate adsorption was
      found to occupy on average from 3.1 to 9.7 sites/nm(2), inversely related to SSA.
      Congruency of oxyanion and Pb(II) adsorption behavior based on fractional site
      occupancy using these values, and a site density analysis suggest that: (i) ion
      binding occurs to singly and doubly coordinated sites, (ii) proton binding occurs
      to singly and triply coordinated sites (ranging from 6.2 to 8 total sites/nm(2),
      in most cases), and (iii) a predominance of (210) and/or (010) faces explains the
      high reactivity of low SSA goethites. The results imply that the macroscopic
      goethite adsorption behavior may be predicted without a need to investigate
      extensive structural details of each specific goethite of interest.

PMID- 18621383
TI  - Mechanism of nitromethane liquid membrane oscillator containing sodium oleate.
AB  - The oscillatory behavior of a liquid membrane oscillator with anionic surfactant
      was investigated in order to understand the oscillation mechanism at the
      molecular level. As a theoretical framework, an approach based on chemical
      kinetics laws has been used. The chosen system involved nitromethane with 2,2(')
      bipyridine as liquid membrane. The aqueous donor phase contained sodium oleate
      and butanol, while sodium chloride was added to the aqueous acceptor phase. It
      was established that the oscillations take place exclusively at the aqueous
      acceptor phase/membrane interface. Therefore, liquid membrane oscillators with
      anionic surfactants behave the same way as oscillators with cationic surfactants
      as to the location of oscillations. An oscillation mechanism involving three
      stages is proposed and confirmed by numerical simulations. The oscillations of
      electrical potential differences between the two aqueous phases are produced by
      sudden adsorption and desorption of anionic surfactant in solvated form and
      butanol at the acceptor/membrane interface. The whole process is controlled by
      the slow diffusion of these species across the liquid membrane. The chaotic
      character of the oscillations was demonstrated by Lyapunov exponents obtained
      from the strange attractor of the system.

PMID- 18621384
TI  - Histological, immunohistochemical and pathological features of the pituitary
      gland of odontocete cetaceans from the Western gulf of Mexico.
AB  - Pituitary glands were recovered from dolphins and small whales found stranded
      along the Texas coast of the Gulf of Mexico over a 15-year period (1991-2006).
      One hundred animals of 14 species were found to be suitable for inclusion in this
      study. Of these, 72 were Atlantic bottlenose dolphins (Tursiops truncatus). Other
      species included were the melon-headed whale (Peponocephala electra), spinner
      dolphin (Stenella longirostris), striped dolphin (Stenella coeruleoalba),
      pantropical spotted dolphin (Stenella attenuata), pygmy sperm whale (Kogia
      breviceps), dwarf sperm whale (Kogia sima), Risso's dolphin (Grampus griseus),
      the short finned pilot whale (Globicephala macrorhyncha), false killer whale
      (Pseudorca crassidens), Fraser's dolphin (Lagenorhynchus hosei), rough-tooth
      dolphin (Steno bredanensis), Gervais's beaked whale (Mesoplodon europaeus) and an
      infant sperm whale (Physeter catodon). The pituitary weights in T. truncatus
      ranged from 0.69 g in a 109-cm long neonate to 3.44 g in a large (277 cm) male.
      More typical weights were in the range of 0.95-2.35 g (mean=1.65+/-0.70 g) The
      cetacean pituitary consisted of two distinct parts, the adenohypophysis and the
      neurohypophysis, which were separated by a thin fibrous membrane in all species
      examined, in contrast to terrestrial mammals in which the parts are apposed and
      joined through a pars intermedia. Cell types were identified with conventional
      stains and immunohistochemistry. Cells positive for adrenocorticotropic hormone,
      follicle stimulating hormone, growth hormone, melanocyte stimulating hormone,
      luteinizing hormone and prolactin were identified with appropriate antibodies.
      Lesions, which were few, included one pituicytoma of the pars nervosa and a
      squamous cyst in T. truncatus, and colloid cysts in several species. Nodular
      aggregates of single cell types were common, probably representing a
      physiological variant.

PMID- 18621385
TI  - Electrocardiogram reading from the perspective of a medium-sized community
      hospital.

PMID- 18621386
TI  - Role of symbiotic and non-symbiotic bacteria in carbon dioxide production from
      hosts infected with Steinernema riobrave.
AB  - Entomopathogenic nematodes of the family Steinernematidae and their mutualistic
      bacteria (Xenorhabdus spp.) are lethal endoparasites of insects. We hypothesized
      that growth of the nematode's mutualistic bacteria in the insect host may
      contribute to the production of cues used by the infective juveniles (IJs) in
      responding to potential hosts for infection. Specifically, we tested if patterns
      of bacterial growth could explain differences in CO2 production over the course
      of host infection. Growth of Xenorhabdus cabanillasii isolated from Steinernema
      riobrave exhibited the characteristic exponential and stationary growth phases.
      Other non-nematode symbiotic bacteria were also found in infected hosts and
      exhibited similar growth patterns to X. cabanillasii. Galleria mellonella larvae
      infected with S. riobrave produced two distinct peaks of CO2 occurring at 25.6-36
      h and 105-16 h post-infection, whereas larvae injected with X. cabanillasii alone
      showed only one peak of CO2, occurring at 22.8-36.2h post-injection. Tenebrio
      molitor larvae infected with S. riobrave or injected with bacteria alone
      exhibited only one peak of CO2 production, which occurred later during S.
      riobrave infection (41.4-64.4h post-infection compared to 20.4-35.9h post
      injection). These results indicate a relationship between bacterial growth and
      the first peak of CO2 in both host species, but not for the second peak exhibited
      in G. mellonella.

PMID- 18621387
TI  - Cellular clot formation in a sipunculan worm: entrapment of foreign particles,
      cell death and identification of a PGRP-related protein.
AB  - Clotting in animals having open or closed circulatory system comprises humoral
      and cellular mechanisms. Sipunculans are a small phylum of non-segmented marine
      worms that do not have a true circulatory system. These worms can form a cellular
      clot without transforming cell-free coelomic fluid into an insoluble mass. The
      clot may also contribute to immune response by entrapping foreign particles. We
      evaluated the formation of a cellular clot ex vivo in the sipunculan Themiste
      petricola after activation through glass contact and sea water, the ability to
      entrap magnetic beads and non-pathogen cyanobacteria particles within the clot,
      and the presence of a peptidoglycan recognition protein S (PGRP-S) antigen in
      cells forming the clot. Our results showed that the clot was formed by homotypic
      aggregation of large granular leukocytes (LGLs), a subtype of cells found in the
      coelomic fluid. Aggregated LGLs served to entrap magnetic beads and non-pathogen
      cyanobacteria particles, and PGRP-S antigen was detected both in non-activated
      LGLs and in activated homotypic aggregates through immunofluorescence, Western
      blot and flow cytometry. Cellular clots were found to be positive to Annexin V
      FITC labelling. Complete disintegration of cytoplasm with shedding of
      microparticles, nuclear isolation and degradation were also observed by light
      microscopy and flow cytometry. In conclusion, cellular clot formation in Themiste
      petricola may serve both haemostatic and immune functions entailing rapid
      activation changes in LGLs, entrapment of foreign particles within a homotypic
      aggregate, and further cell death.

PMID- 18621388
TI  - Structural, biochemical, and in vivo investigations of the threonine synthase
      from Mycobacterium tuberculosis.
AB  - Threonine biosynthesis is a general feature of prokaryotes, eukaryotic
      microorganisms, and higher plants. Since mammals lack the appropriate synthetic
      machinery, instead obtaining the amino acid through their diet, the pathway is a
      potential focus for the development of novel antibiotics, antifungal agents, and
      herbicides. Threonine synthase (TS), a pyridoxal-5-phosphate-dependent enzyme,
      catalyzes the final step in the pathway, in which L-homoserine phosphate and
      water are converted into threonine and inorganic phosphate. In the present
      publication, we report structural and functional studies of Mycobacterium
      tuberculosis TS, the product of the rv1295 (thrC) gene. The structure gives new
      insights into the catalytic mechanism of TSs in general, specifically by
      suggesting the direct involvement of the phosphate moiety of the cofactor, rather
      than the inorganic phosphate product, in transferring a proton from C4' to
      C(gamma) in the formation of the alphabeta-unsaturated aldimine. It further
      provides a basis for understanding why this enzyme has a higher pH optimum than
      has been reported elsewhere for TSs and gives rise to the prediction that the
      equivalent enzyme from Thermus thermophilus will exhibit similar behavior. A
      deletion of the relevant gene generated a strain of M. tuberculosis that requires
      threonine for growth; such auxotrophic strains are frequently attenuated in vivo,
      indicating that TS is a potential drug target in this organism.

PMID- 18621389
TI  - Probing conserved helical modules of portal complexes by mass spectrometry-based
      hydrogen/deuterium exchange.
AB  - The Double-stranded DNA bacteriophage P22 has a ring-shaped dodecameric complex
      composed of the 84 kDa portal protein subunit that forms the central channel of
      the phage DNA packaging motor. The overall morphology of the P22 portal complex
      is similar to that of the portal complexes of Phi29, SPP1, T3, T7 phages and
      herpes simplex virus. Secondary structure prediction of P22 portal protein and
      its threading onto the crystal structure of the Phi29 portal complexes suggested
      that the P22 portal protein complex shares conserved helical modules that were
      found in the dodecameric interfaces of the Phi29 portal complex. To identify the
      amino acids involved in intersubunit contacts in the P22 portal ring complexes
      and validate the threading model, we performed comparative hydrogen/deuterium
      exchange analysis of monomeric and in vitro assembled portal proteins of P22 and
      the dodecameric Phi29 portal. Hydrogen/deuterium exchange experiments provided
      evidence of intersubunit interactions in the P22 portal complex similar to those
      in the Phi29 portal that map to the regions predicted to be conserved helical
      modules.

PMID- 18621390
TI  - Factors associated with pneumococcal carriage in healthy Dutch infants: the
      generation R study.
AB  - OBJECTIVE: To study the prevalence, risk factors, and dynamics of pneumococcal
      carriage in infancy. STUDY DESIGN: In a population-based prospective cohort study
      conducted in Rotterdam, the Netherlands between June 2003 and November 2006,
      nasopharyngeal swabs were obtained from children at age of 1.5, 6, and 14 months.
      Data on risk factors were obtained from midwives, hospital registries, and
      questionnaires. RESULTS: The prevalence of pneumococcal carriage increased from
      8.3% at age 1.5 months (n = 627) to 31.3% at age 6 months (n = 832) and 44.5% at
      age 14 months (n = 757). The prevalence of serotypes covered by the 7-valent
      conjugate increased from 3.0% to 16.2% and 27.7% at these respective ages. Having
      siblings (adjusted odds ratio [aOR] = 4.33; 95% confidence interval [CI] = 1.22
      to 15.35) and day care attendance (aOR = 3.05, 95% CI = 1.88 to 4.95 at 6 months;
      aOR = 2.78, 95% CI 1.= 70 to 4.55 at 14 months) were associated with pneumococcal
      carriage. Pneumococcal carriage at age 6 months was associated with pneumococcal
      carriage at age 14 months (aOR = 2.43; 95% CI = 1.50 to 3.94). Pneumococcal
      carriage was not associated with sex, maternal smoking, maternal educational
      level, or breast-feeding. CONCLUSIONS: The prevalence of serotypes covered by the
      7-valent conjugate vaccine increased in the first year of life. Siblings, day
      care attendance, and previous pneumococcal carriage were independent factors
      associated with pneumococcal carriage.

PMID- 18621391
TI  - Association of staphylococcal superantigen-specific immunoglobulin e with mild
      and moderate atopic dermatitis.
AB  - OBJECTIVE: To examine the frequency of allergic sensitization to staphylococcal
      superantigens in young children with mild to moderate atopic dermatitis (AD).
      STUDY DESIGN: AD severity was assessed with objective Scoring AD. Serum IgE to
      staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin
      1 were measured with ImmunoCAP. Comparisons between mild AD and moderate AD were
      performed by using logistic regressions. RESULTS: The prevalence of allergic
      sensitization to staphylococcal superantigens in patients with mild and moderate
      AD was 38% and 63%, respectively. Allergic sensitization to staphylococcal
      superantigens, particularly SEA and SED, was found to be associated with moderate
      AD, compared with mild AD. CONCLUSIONS: Our results suggest that allergic
      sensitization to staphylococcal superantigens is common even in young children
      with mild to moderate AD, and such sensitization may contribute to the disease
      severity of these patients.

PMID- 18621392
TI  - Maturation of rod function in preterm infants with and without retinopathy of
      prematurity.
AB  - OBJECTIVES: To establish normal development of rod electroretinograms in preterm
      infants and to assess the effects of retinopathy of prematurity (ROP). STUDY
      DESIGN: We measured 88 Naka-Rushton functions from 41 preterm infants at
      maturities from 30 to 72 weeks postmenstrual age (PMA). Outcomes (log sigma,
      retinal sensitivity and V(max), retinal responsivity) were compared between
      control (no ROP), untreated ROP, and treated ROP. RESULTS: In control infants,
      sensitivity increased by 1.5 log units from 30 to 40 weeks PMA and by a further
      0.5 log units by 50 weeks PMA but was 0.5 log units less than in similarly
      mature, healthy, term-born infants. Average retinal responsivity increased from
      23 microV to 90 microV between 30 and 40 weeks PMA and was 35 muV greater at 40
      weeks PMA than in similarly-mature term-born infants. At around 36 weeks PMA,
      (when onset of ROP peaks), infants with untreated ROP had average retinal
      sensitivity 0.2 log units lower than control infants; sensitivity was reduced
      further in infants treated for ROP. Retinal responsiveness did not differ between
      control subjects and untreated infants with ROP but was greatly reduced in
      infants treated for ROP. CONCLUSIONS: Maturation of rod sensitivity appears to be
      slowed by preterm birth whereas maturation of rod responsivity is accelerated.
      ROP reduces retinal sensitivity, and treated ROP reduces both sensitivity and
      responsivity.

PMID- 18621393
TI  - Effects of influenza plus pneumococcal conjugate vaccination versus influenza
      vaccination alone in preventing respiratory tract infections in children: a
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the effects of influenza vaccination with or without
      heptavalent pneumococcal conjugate vaccination on respiratory tract infections
      (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo
      controlled trial comprising 579 children age 18 to 72 months with a previous
      history of physician-diagnosed RTI, recruited between 2003 and 2005. The children
      were assigned to 2 doses of parenteral inactivated trivalent subunit influenza
      plus heptavalent pneumococcal conjugate vaccination (TIV+PCV7), influenza plus
      placebo vaccination (TIV+plac), or control hepatitis B virus vaccination plus
      placebo (HBV+plac). Main outcome measures were febrile RTI and related polymerase
      chain reaction (PCR)-confirmed influenza, primary care visits, antibiotic
      prescriptions, and acute otitis media (AOM) episodes. RESULTS: During influenza
      seasons, febrile RTI were reduced by 24% (95% confidence interval [CI] = 1% to
      42%) in the TIV+PCV7 group and by 13% (95% CI = -12% to 32%) in the TIV+plac
      group compared with the control group. The occurrence of PCR-confirmed influenza
      was reduced by 52% (95% CI = 7% to 75%) in the TIV+PCV7 group and by 51% (95% CI
      = 3% to 75%) in the TIV+plac group. Episodes of AOM were reduced by 57% (95% CI =
      6% to 80%) in the TIV+PCV7 group and by 71% (95% CI = 30% to 88%) in the TIV+plac
      group. Outside of the influenza seasons, no significant effects of vaccinations
      were demonstrated on the studied outcomes. CONCLUSIONS: During influenza seasons,
      influenza vaccination with or without pneumococcal conjugate vaccination
      substantially reduced cases of confirmed influenza and AOM episodes.

PMID- 18621394
TI  - Quantitative RT-PCR detection of colorectal tumor cells in peripheral blood--a
      systematic review.
AB  - BACKGROUND: Twenty percent to 40% of patients with node-negative colorectal
      cancer die of metastatic disease. Detection of cancer cell dissemination has been
      proposed as a tool to select patients at highest risk for recurrence. In this
      review, we summarize the evidence for detection with quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) assays of circulating tumor
      cells (CTCs) in peripheral blood of colorectal cancer patients. MATERIALS AND
      METHODS: Pubmed and Embase were systematically searched for all English
      publications relevant to circulating cancer cells, peripheral blood, quantitative
      RT-PCR (q-RT-PCR), and colorectal cancer. Cross-references and the "related
      articles" function were used to broaden the search. Manuscripts reporting on the
      results of nonquantitative RT-PCR assays were excluded. The study methodology,
      CTCs detection rates in peripheral blood, and prognostic value were reviewed.
      RESULTS: Twelve manuscripts on qRT-PCR were retrieved. Stage dependence was found
      for detection of CTCs in four of 10 studies. From univariate analysis performed
      for disease-free survival and overall survival in 4 of 12 studies, there was
      evidence (P < 0.05) for an effect of the detection of CTCs with qRT-PCR. None of
      the included trials identified detection of CTCs in peripheral blood as an
      independent predictor of survival. CONCLUSION: Quantification of CTCs in
      peripheral blood holds promise in predicting stage and outcome in colorectal
      cancer patients. At present, evidence from the literature is too scarce to
      integrate quantitative RT-PCR assays to detect CTCs into the management of
      colorectal cancer.

PMID- 18621395
TI  - Autonomic regulation of liver regeneration after partial hepatectomy in mice.
AB  - BACKGROUND/AIMS: The autonomic vagus nerve is thought to play an essential role
      in liver regeneration since hepatic vagotomy delays hepatic DNA synthesis.
      However, how the parasympathetic vagus nerve is involved in liver regeneration
      remains obscure. Kupffer cells are located in liver sinusoids adjacent to
      hepatocytes and might regulate liver regeneration by releasing interleukin-6 (IL
      6). The present study examines the role of the vagus nerve and how Kupffer cells
      are involved in parasympathetic nerve-mediated liver regeneration in mice.
      METHODS: We performed surgical vagotomy of the hepatic branch and then partial
      hepatectomy (PH); some mice received acetylcholine (ACh) agonist/antagonist
      before PH. We then evaluated liver regeneration and signal transducer and
      activator of transcription-3 (STAT3) activation. We also investigated whether ACh
      stimulates IL-6 release from Kupffer cells. RESULTS: Surgical vagotomy impaired
      liver regeneration. STAT3, which is activated by IL-6 after hepatectomy and plays
      a pivotal role in liver regeneration, was less activated in vagotomized mice
      after PH. Post-PH STAT3 activation was recovered by administering vagotomized
      mice with an ACh agonist. Furthermore, ACh stimulated IL-6 release in Kupffer
      cells in vitro. CONCLUSION: The parasympathetic system (vagus nerve) contributes
      to liver regeneration after hepatectomy by stimulating IL-6 release from Kupffer
      cells followed by STAT3 activation in hepatocytes.

PMID- 18621396
TI  - PKC and MLCK-dependent, cytokine-induced rat coronary endothelial dysfunction.
AB  - BACKGROUND: Heart disease is one of the leading causes of death in the United
      States, killing nearly one million people every year. Inflammatory mediators or
      cytokines are released following myocardial infarction and ischemia/reperfusion
      injury. These cytokines, of which interleukin-1beta, interleukin-6, and tumor
      necrosis factor-alpha (TNF-alpha) are among the most important, propagate the
      activation of a multitude of signaling pathways, such as the protein kinase C
      (PKC) and myosin light chain kinase (MLCK) pathways, which lead to deleterious
      changes in the structure and function of the coronary microvascular endothelium.
      METHODS: The effects of cytokines on rat heart microvascular endothelial cell
      monolayer integrity, PKC activity, and adherens junction protein alteration were
      examined. Further, an in vivo rat coronary ischemia/reperfusion injury model was
      used to determine vascular leakage and TNF-alpha release. RESULTS: Administration
      of the above mentioned cytokines to cell monolayers resulted in significant
      increases in PKC activation, gap formation, and hyperpermeability across the
      monolayer and beta-catenin phosphorylation/reorganization. Inhibition of
      conventional PKC and MLCK attenuated permeability increases. Ischemia/reperfusion
      injury to the left ventricle resulted in TNF-alpha release as well as
      conventional PKC- and MLCK-dependent protein extravasation from the circulation
      to the heart tissue. CONCLUSION: These results identify the conventional PKC and
      MLCK pathways as important factors in coronary endothelial dysfunction elicited
      by IR injury and cytokine release. Further examination of these molecular
      signaling cascades has the potential of identifying targets for therapeutic
      intervention following ischemic events in the heart.

PMID- 18621397
TI  - Two-port laparoscopic appendectomy: minimizing the minimally invasive approach.
AB  - BACKGROUND: Three laparoscopic ports are traditionally required to complete a
      laparoscopic appendectomy. We describe a novel, innovative 2-port laparoscopic
      technique, in which intracorporeal appendectomy can be completed safely with
      standard instrumentation. MATERIALS AND METHODS: Eight consecutive patients were
      prospectively assigned to undergo 2-port laparoscopic appendectomies for presumed
      appendicitis. The technique involves the placement of one 12-mm infraumbilical
      port for the working instruments and one 5-mm left lower quadrant port for the
      camera. A suture is tied in a loop to the anterior abdominal wall in the right
      lower quadrant, which is subsequently used as an axle. A pretied suture placed on
      the appendix is passed through the loop suture and then through the port to the
      outside of the abdomen. This technique allows exposure of the base of the
      appendix and compensates for the lack of the third port usually required for the
      retraction of the appendix. The mesoappendix and appendix are stapled and removed
      from the abdomen in an extrication bag. RESULTS: All 8 laparoscopic procedures
      were completed without difficulty. The mean operative time was 64.1 min. Length
      of hospitalization was 1 d or less. No major complications were encountered. One
      minor postoperative complication occurred in which the patient developed
      periumbilical cellulitis, which was completely resolved at the 1-wk postoperative
      visit. CONCLUSION: In times where surgeons are focusing on transluminal
      approaches to access the abdominal cavity, we favor laparoscopy for the enhanced
      exposure, instrument diversity, and overall patient safety. Two-port laparoscopic
      appendectomy is a safe, novel laparoscopic technique, which minimizes minimally
      invasive surgery even further to a new level of decreased invasiveness and
      improved cosmesis.

PMID- 18621398
TI  - Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus
      aureus clearance.
AB  - BACKGROUND: Staphylococcus aureus is the most common cause of healthcare
      associated pneumonia. Despite the significant morbidity and mortality associated
      with the disease, animal models of S. aureus pneumonia are rare. MATERIALS AND
      METHODS: We examined the pathogenicity of four different strains of S. aureus
      (both methicillin-sensitive and -resistant as well as Panton-Valentine leukocidin
      positive and -negative) in four strains of immunocompetent inbred and outbred
      mice (FVB/N, C57Bl/6, BALB/c, ND4; n = 148). The immunological basis for the
      development of murine S. aureus pneumonia was then determined by selectively
      depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset
      of infection. An additional cohort of animals was rendered immunosuppressed by
      induction of abdominal sepsis via cecal ligation and puncture 2, 4, or 7 d prior
      to the onset of pneumonia. RESULTS: Nearly all immunocompetent mice survived,
      regardless of which strain of S. aureus was used or which strain of mouse was
      infected. Among animals with immune depletion or prior immunosuppression,
      survival was decreased only following neutrophil depletion (26% versus 90% alive
      at 7 d, P < 0.0001). Compared to immunocompetent animals, neutrophil-depleted
      mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and
      40 h but had no difference in levels of bacteremia. Neutrophil-depleted mice also
      had elevated levels of pulmonary monocyte chemotactic protein-1 (822 pg/mL versus
      150 pg/mL, P < 0.05). In contrast, pulmonary histological appearance was similar
      in both groups as was dry/wet lung weight. CONCLUSIONS: These results suggest
      that neutrophils play a critical role in the host response to S. aureus
      pneumonia, and the survival differences observed in neutrophil-depleted mice are
      associated with alterations in bacterial clearance and pulmonary cytokine
      response.

PMID- 18621399
TI  - Timing and targeting of cell-based VEGF165 gene expression in ischemic tissue.
AB  - BACKGROUND: Therapeutic angiogenesis has become a key technology in experimental
      and clinical medicine. Only few data are available on the effects of timing and
      targeting of therapeutic proteins after cell-based gene transfer. This work
      investigates such effects after temporary expression of vascular endothelial
      growth factor 165 (VEGF(165)), the most commonly used angiogenic protein for
      therapeutic purposes. METHODS: We established a cell-based gene-transfer model
      using fibroblasts to temporarily produce VEGF(165). Cells were implanted into 40
      rats. Protein expression and angiogenic effects were measured by PCR,
      immunohistology, and microangiography. To determine an improvement for survival
      of ischemically challenged tissue, cells were implanted in an ischemic flap model
      at different locations and time points. RESULTS: After implantation of modified
      cells, a temporary increase was found in the target tissue for VEGF(165),
      endothelial cell counts, and capillary network formations. Four wk later,
      histological alterations in the target tissue area were not different from
      controls. Implantation of modified cells into flap plus wound margin 1 wk before
      surgery showed significant improvement of tissue survival demonstrated by
      planimetric measurements and blood vessels counting in the target tissue.
      CONCLUSION: In our model, temporary expression of VEGF(165) induces
      therapeutically relevant angiogenesis and improves blood supply only if applied 1
      wk before ischemia. It is essential to include the surrounding area for induction
      of angiogenesis in this model. In contrast, the angiogenic effects are not
      effective in the target area and its surrounding tissue, if therapeutic gene
      expression is started during onset of ischemia or 2 wk before ischemia in this
      model.

PMID- 18621400
TI  - The protective effect of CAPE on hepatic ischemia/reperfusion injury in rats.
AB  - BACKGROUND/AIMS: The transcription factor nuclear factor-kappa B (NF-kappaB)
      exerts a pivotal role in the pathogenesis of hepatic ischemia/reperfusion (I/R)
      injury. Caffeic acid phenyl ester (CAPE), a potent and specific NF-kappaB
      inhibitor, presents protective effects on I/R injury in some tissues. This study
      aimed to evaluate the effect of CAPE on hepatic I/R injury in rats. MATERIALS AND
      METHODS: Wistar rats were submitted to a sham operation, 60 min ischemia, or 60
      min ischemia plus saline or CAPE treatment followed by 6 h reperfusion. Liver
      tissue injury was evaluated by alanine aminotransferase, aspartate
      aminotransferase, and tissue glutathione measurement, and histological damage
      score. Apoptotic hepatocytes were determined by the transferase-mediated dUTP
      biotin nick-end labeling assay. Hepatic neutrophil accumulation was assessed by
      the naphthol method. Lipid peroxidation and NF-kappaB activation were evaluated
      by 4-hydroxynonenal and NF-kappaB p65 immunohistochemistry, respectively.
      RESULTS: Animals submitted to ischemia showed a marked increase of alanine
      aminotransferase and aspartate aminotransferase after reperfusion, but with lower
      levels in CAPE group. Tissue glutathione content declined gradually during
      ischemia to reperfusion and was partially recovered with CAPE treatment. The
      histological damage score, apoptosis index, and neutrophil infiltration, as well
      as 4-hydroxynonenal and NF-kappaB p65 nuclear labeling, were higher in the liver
      of animals submitted to I/R compared to the ischemia group. However, the CAPE
      treatment significantly reduced all of these alterations. CONCLUSIONS: CAPE was
      able to protect the liver against normothermic I/R injury in rats. This effect
      may be associated with the inhibition of the NF-kappaB signaling pathway and
      decrease of the acute inflammatory response following I/R in the liver.

PMID- 18621401
TI  - Tissue-engineered spleen protects against overwhelming pneumococcal sepsis in a
      rodent model.
AB  - BACKGROUND/PURPOSE: Solid organs production is an ultimate goal of tissue
      engineering. After refining a technique for intestinal engineering, we applied it
      to a solid organ, the spleen. Overwhelming postsplenectomy sepsis results in
      death in nearly half of all cases. This risk is pronounced in children. Necrosis
      of autotransplanted spleen slices occurs prior to regeneration. We postulate that
      tissue engineering techniques might be superior. METHODS: Four groups of Lewis
      rats were compared: sham laparotomy, tissue-engineered spleen (TES), traditional
      spleen slices, and splenectomy. TES was generated from splenic units,
      multicellular components of juvenile spleen implanted on a biodegradable polymer
      scaffold, and spleen slices were derived from age-matched juveniles. Pneumococcal
      sepsis was induced at wk 16, and survival curves were constructed. RESULTS:
      Tissue-engineered spleen protected against pneumococcal septicemia with a
      survival proportion of 85.7% compared with 41.17% of splenectomized animals.
      Spleen slice was also protective with 71.43% survival. Compared with splenectomy,
      control and TES groups were statistically significant (P = 0.0002, P = 0.0087;
      hazard ratio of splenectomy = 5.493) and the Slice group was nearly statistically
      significant (P = 0.0642, hazard ratio of splenectomy = 2.673). CONCLUSIONS: TES
      is a novel application of tissue engineering to splenic regeneration and creates
      a functional spleen. This approach could be advantageous in severe pediatric
      trauma.

PMID- 18621402
TI  - Huntington's disease: modeling the gait disorder and proposing novel treatments.
AB  - Huntington's disease is a movement disorder originated from malfunctioning of
      Basal Ganglia (BG). There are some models for this disease, most of them being
      conceptual. So, it seems that considering all physiological information and
      structural specifications to develop a holistic model is needed. We introduce a
      computational model based on experimental and physiological findings. Parts of
      the brain known to be involved in Huntington's disease are all considered in our
      model and most features of the movement disorders have been appeared in the
      model. This mathematical model has considered the involved parts of the brain in
      a fairly accurate way, explaining the behavior and mechanism of the disease
      according to the physiological information. Our model has several advantages. It
      is able to simulate the normal and Huntington's disease stride time intervals. It
      shows how the present treatment, i.e. diazepam, is able to ameliorate the gait
      disorder. In this research we assessed the effects of changing some
      neurotransmitter levels in order to propose new treatments. Although we showed
      that gamma amino butyric acid (GABA) blockers reduce Huntington's disease
      movement disorder, but we discussed that it is unfair to use this route for
      treatment. We evaluated our model response to increment of GABA, alone and
      observed that the gait disorder was strengthened. Our novel idea in this regard
      is resuscitation of BG loop in order to maintain its major physiological
      functions, and at the same time raising the threshold in order to weaken the
      internal disturbances. Our last idea about BG treatment is to decrease glutamate.
      Our model was able to show the effectiveness of this treatment on Huntington's
      disease disturbances. We propose that experimental studies should be designed in
      which these two novel methods of treatment will be evaluated. This validation
      would implement a milestone in treatment of such a debilitating disease at
      Huntington.

PMID- 18621403
TI  - Modeling the precision and robustness of Hunchback border during Drosophila
      embryonic development.
AB  - During anterior-posterior axis specification in the Drosophila embryo, the
      Hunchback (Hb) protein forms a sharp boundary at the mid-point of the embryo with
      great positional precision. While Bicoid (Bcd) is a known upstream regulator for
      hb expression, there is evidence to suggest that Hb effectively filters out
      "noisy" data received from varied Bcd gradients. We use mathematical models to
      explore simple regulatory networks which filter out such noise to produce a
      precise Hb boundary. We find that in addition to Bcd and Hb, at least one freely
      evolving protein is necessary. An automated search yields a number of examples of
      three-protein networks exhibiting the desired precision. In all such networks, Hb
      diffuses much slower than the third protein. In addition, the action of Hb on the
      third protein is the opposite of the action of the third protein on hb (i.e. if
      Hb activates the third protein, then the third protein inhibits hb expression,
      and vice versa). Most of the discovered systems satisfy the known biological
      properties, that Bcd activates hb, and that Hb activates its own expression. We
      find that all network topologies satisfying these constraints arise among the
      networks exhibiting the desired precision. Investigating the dynamics of these
      networks, we find that under a general class of non-uniform initial conditions,
      Bcd can be eliminated from the system and the spatiotemporal evolution of these
      two proteins alone is sufficient to recapture the dynamics. We hypothesize that
      Bcd is needed only to spatially disturb the gradient of the third protein, and
      then becomes unnecessary in the further evolution of the Hb border. This provides
      a possible explanation as to why the Hb dynamics are robust under perturbations
      of the Bcd gradient. Under this hypothesis, other proteins would be able to
      assume the role of Bcd in our simulations (possibly in the case of evolutionary
      divergences or a redundancy in the process), with the only constraint that they
      act to positively regulate hb.

PMID- 18621404
TI  - Serotonergic approaches in the development of novel antipsychotics.
AB  - Schizophrenia is a chronic, debilitating neuropsychological disease characterised
      by positive, negative, and cognitive deficits. In recent years, new
      pharmacological treatment strategies have been developed to treat the sequalae of
      schizophrenia based upon more selective receptor activity profiles in the hope
      that treatment efficacy can be increased without inducing the side-effect
      profiles seen with current available therapies. One such strategy involves the
      development of combined (partial) 5-HT(1A) agonists and D(2) receptor (partial)
      antagonists such as bifeprunox, SLV313, F15063 and SSR-181507 in an attempt to
      increase therapeutic efficacy of all symptom domains whilst alleviating adverse
      side effects. Other novel drugs including SLV310 and SLV314 combine selective
      serotonin reuptake inhibition (SSRI) functionality with D(2) receptor antagonism
      in an attempt to not only improve schizophrenic symptoms, but to also relieve
      other affective disorders intricately linked with the disorder. The main scope of
      this review will evaluate the major preclinical and clinical pharmacological
      findings concerning the aforementioned strategies and pharmacological agents, and
      compare their therapeutic potential with currently available antipsychotics;
      however, recent developments at other emerging serotonergic targets such as 5
      HT(2C), 5-HT(6) and 5-HT(7) receptors will also be considered.

PMID- 18621405
TI  - Banning smoking in restaurants: effects on behavioural intentions.

PMID- 18621406
TI  - Centrally administered verapamil prevents the autonomic reaction to visceral pain
      in sheep.
AB  - The significant role of voltage gated calcium channels (VGCC) L-type antagonists
      used concomitantly with opioids in attenuation of clinical pain has been
      confirmed. The aim of this study was to evaluate the effect of centrally
      administered verapamil on behavior and biochemical parameters in sheep that have
      undergone experimental duodenal distension (DD) and to determine whether
      verapamil exerts any anti-nociceptive effects under these conditions. The study
      was carried out using 24 mature crossbred ewes, each weighing 38-43 kg.
      Verapamil, a VGCC blocker, was administered through an intracerebroventricular
      cannula at the following doses: 0.25, 0.5, 1.0 and 2.0mg in toto. Ten minutes
      later experimental DD was conducted by insertion and the distension of rubber
      balloon (containing 40 ml of warm water) inserted into sheep duodenum. After 5
      min of mechanical DD the following reactions were then observed: the significant
      increase in behavioral pain responses, i.e. tachycardia, hyperventilation,
      inhibition of reticulo-ruminal contractions (70% approximately, during 15 min),
      an increase of plasma catecholamine concentration (over 7-fold increase of
      epinephrine during 2h following DD, 2-times norepinephrine and +/-80% increase of
      dopamine). Verapamil infusion administered 10 min prior to DD decreased intensity
      of visceral pain responses, such as: behavioral changes, tachycardia,
      hyperventilation, inhibition of the reticulo-rumen motility and efficiently
      prevented the appearance of catecholamine release. These data demonstrated that
      the development and persistence of duodenal hyperalgesia depends on the
      activation of Ca(2+) ion flux leading to neurotransmitters release and modulation
      of membrane excitability. The observed antinociceptive action of VGCCs type-L
      blockers suggests that these channels play a crucial role in the modulation of
      acute visceral hyperalgesia in sheep.

PMID- 18621407
TI  - Electroencephalographic evaluation of gold wire implants inserted in acupuncture
      points in dogs with epileptic seizures.
AB  - The purpose of this study was to evaluate both, clinically and with
      electroencephalographic (EEG) recordings, the effect of gold wire implants in
      acupuncture points in dogs with uncontrolled idiopathic epileptic seizures.
      Fifteen dogs with such diagnosis were enrolled in the study. A first EEG
      recording was performed in all dogs under anaesthesia with xylazine (1mg/kg) and
      propofol (6 mg/kg) before the treatment protocol, and a second EEG was performed
      15 weeks later. Relative frequency power, intrahemispheric coherence available
      through EEG, number of seizures and seizure severity were compared before and
      after treatment using a Wilcoxon signed-rank test. There were no significant
      statistical differences before and after treatment in relative power or in
      intrahemispheric coherence in the EEG recording. However, there was a significant
      mean difference in seizure frequency and seizure severity between control and
      treatment periods. After treatment, nine of the 15 dogs (60%) had at least a 50%
      reduction in seizures frequency during the 15 weeks established as follow-up of
      this treatment.

PMID- 18621408
TI  - Active fiber composites for the generation of Lamb waves.
AB  - Active fiber composites (AFC) are thin and conformable transducer elements with
      orthotropic material properties, since they are made of one layer of
      piezoelectric ceramic fibers. They are suitable for applications in structural
      health monitoring systems (SHM) with acoustic non-destructive testing methods
      (NDT). In the presented work the transfer behavior of an AFC as an emitter of
      transient elastic waves in plate-like structures is investigated. The wave field
      emitted by an AFC surface bonded on an isotropic plate was simulated with the
      finite-difference method. The model includes the piezoelectric element and the
      plate and allows the simulation of the elastic wave propagation. For comparison
      with the model experiments using a laser interferometer for non-contact
      measurements of particle velocities at different points around the AFC on the
      surface of the plate were performed. Transfer functions defined as the ratio of
      the electric voltage excitation signal and the resulting surface velocity at a
      specific point are separately determined for the two fundamental Lamb wave modes.
      In order to take the orthotropic behavior of the AFC into account the transfer
      functions are determined for several points around the AFC. Results show that the
      AFC is capable to excite the fundamental symmetric and antisymmetric Lamb wave
      mode. The antisymmetric mode is mainly radiated in the direction of the
      piezoelectric fibers, while the symmetric mode is spread over a larger angle. The
      amplitudes of the emitted waves depend on the frequency of the excitation as well
      as on the geometric dimensions of the transducer.

PMID- 18621409
TI  - Human herpesvirus-6 infection induces the reorganization of membrane microdomains
      in target cells, which are required for virus entry.
AB  - Cell-membrane raft microdomains are important for successful infection by several
      viruses. However, their role in the cell-entry process of human herpesvirus-6
      (HHV-6) is unknown. Here we tested whether HHV-6 requires cell-membrane rafts for
      its entry. When cell-membrane rafts were disrupted by cholesterol depletion,
      target-cell entry by HHV-6 was inhibited, although the virus bound normally to
      the cells. HHV-6 infectivity was partially rescued by adding exogenous
      cholesterol. Interestingly, the HHV-6 cellular receptor, CD46, was found in the
      rafts after virus attachment, but not in the rafts of uninfected cells,
      indicating that HHV-6 infection induces the re-location of its receptor into the
      rafts. Furthermore, glycoprotein Q1, part of a viral glycoprotein complex that
      binds CD46, was also associated with rafts immediately after infection. These
      data suggest that cellular-membrane lipid rafts are important in viral entry and
      that HHV-6 may enter the target cells via the rafts.

PMID- 18621410
TI  - A computational model that recovers the 3D shape of an object from a single 2D
      retinal representation.
AB  - Human beings perceive 3D shapes veridically, but the underlying mechanisms remain
      unknown. The problem of producing veridical shape percepts is computationally
      difficult because the 3D shapes have to be recovered from 2D retinal images. This
      paper describes a new model, based on a regularization approach, that does this
      very well. It uses a new simplicity principle composed of four shape constraints:
      viz., symmetry, planarity, maximum compactness and minimum surface. Maximum
      compactness and minimum surface have never been used before. The model was tested
      with random symmetrical polyhedra. It recovered their 3D shapes from a single
      randomly-chosen 2D image. Neither learning, nor depth perception, was required.
      The effectiveness of the maximum compactness and the minimum surface constraints
      were measured by how well the aspect ratio of the 3D shapes was recovered. These
      constraints were effective; they recovered the aspect ratio of the 3D shapes very
      well. Aspect ratios recovered by the model were compared to aspect ratios
      adjusted by four human observers. They also adjusted aspect ratios very well. In
      those rare cases, in which the human observers showed large errors in adjusted
      aspect ratios, their errors were very similar to the errors made by the model.

PMID- 18621411
TI  - Photocatalytic and photoelectrocatalytic humic acid removal and selectivity of
      TiO(2) coated photoanode.
AB  - In this study, photocatalytic (PC) and photoelectrocatalytic (PEC) treatment
      methods were comparatively investigated as a possible means of removing humic
      acid (HA) following absorbance at 254 nm (UV(254)) and total organic carbon (TOC)
      analysis. The enhanced HA degradation rates were obtained in the PEC system over
      the conventional PC process under acidic, neutral and alkaline conditions.
      Preliminary and binary experiments were performed to determine the selectivity of
      the photoanode in terms of HA and chloride oxidation. TOC, chlorine and
      photocurrent parameters proved that HA was selectively removed before chlorine
      generation. The inhibitory effect of carbonate ions on the performance of
      photoanode was also studied under different pH values.

PMID- 18621412
TI  - Pesticides in fluvial wetlands catchments under intensive agricultural
      activities.
AB  - A survey on pesticides (73 compounds) in the Bay St. Francois wetland and its
      catchment (part of the wetlands of Lake St. Pierre area [St. Lawrence River,
      Quebec]) was achieved in 2006. The metabolites as well as the active ingredients
      of pesticides (11 compounds) were detected in the wetland and its catchment. This
      wetland ecosystem was active in the degradation of agricultural pesticides (e.g.,
      atrazine). The measured pesticides were individually below the criteria for
      aquatic species in natural water, except chlorpyrifos. Overall, the pesticides
      lost from agricultural field towards the streams were <1% of the quantity
      applied. The environmental fates of the pesticides were found to vary according
      to the size of the watershed. Over large catchments, half-life times were
      important in terms of global loss from the agricultural lands to wetlands whereas
      over small catchments, soil organic carbon/water distribution coefficient (Koc)
      was an important term for pesticides losses to water system since half-life times
      were not limiting factors.

PMID- 18621413
TI  - Effect of allopurinol on damage caused by free radicals to cryptorchid testes.
AB  - Cryptorchidism causes apoptosis of germ cells. It has been suggested that the
      redox regulatory system is involved in this process. The free radicals produced
      are thought to be generated during the production of uric acid, a reaction
      catalyzed by xanthine oxidase. This enzyme is inhibited by allopurinol; however,
      the role of allopurinol in neonate rats with inguinal cryptorchidism has not been
      assessed yet. Sixty male Wistar rats were used and five groups were formed: a
      control, a sham, a sham group with allopurinol administration and two groups with
      surgical unilateral cryptorchidism, which either did not receive, or received,
      allopurinol. The rats were assessed at 40 days post-partum. Reactive oxygen
      species concentration and epithelial area were measured and the
      histopathological, apoptotic and cellular proliferation indexes were determined.
      We found a decrease in reactive oxygen species, histopathological and apoptotic
      indexes and an increase in proliferation index and epithelial area in rats with
      cryptorchidism treated with allopurinol in comparison with rats with untreated
      cryptorchidism. We suggest that the over-production of reactive oxygen species
      plays an important role in the damage of the cryptorchid testes. Allopurinol
      administration decreases reactive oxygen species concentrations as well as the
      damage to the germ epithelium.

PMID- 18621414
TI  - Vitamin D signaling in immune-mediated disorders: Evolving insights and
      therapeutic opportunities.
AB  - 1,25(OH)(2)D(3), the active form of vitamin D, is a central player in calcium and
      bone metabolism. More recently, important immunomodulatory effects have been
      attributed to this hormone. The widespread presence of the vitamin D receptor
      (VDR) in the immune system and the expression of the enzymes responsible for the
      synthesis of the active 1,25(OH)(2)D(3) regulated by specific immune signals,
      even suggest a paracrine immunomodulatory role for 1,25(OH)(2)D(3). Additionally,
      the different molecular mechanisms used by 1,25(OH)(2)D(3) to exert its
      immunomodulatory effects prove of a broad action radius for this compound. Both,
      the effects of vitamin D deficiency and/or absence of the VDR as well as
      intervention with pharmacological doses of 1,25(OH)(2)D(3) or one of its less
      calcemic analogs, affects immune system behavior in different animal models of
      immune-mediated disorders, such as type 1 diabetes. This review aims to summarize
      the data as they stand at the present time on the role of vitamin D in the
      pathogenesis of immune-mediated disorders, with special focus on type 1 diabetes,
      and on the therapeutic opportunities for vitamin D in the prevention and
      treatment of this autoimmune disease in mouse models and humans.

PMID- 18621415
TI  - Membrane allocation profiling: a method to characterize three-dimensional cell
      shape and attachment based on surface reconstruction.
AB  - Three-dimensional surface reconstructions from high resolution image stacks of
      biological specimens, observed by confocal microscopy, have changed the
      perspective of morphological understanding. In the field of cell-cell or cell
      substrate interfaces, combining these two techniques leads to new insights yet
      also creates a tremendous amount of data. In this article, we present a technique
      to reduce large, multidimensional data sets from confocal microscopy into one
      single curve: a membrane allocation profile. Reconstructed cells are represented
      in a three-dimensional surface from image sections of individual cells. We
      virtually cut segments of the reconstructed cell membrane parallel to the
      substrate and calculate the surface areas of each segment. The obtained membrane
      allocation profiles lead to morphological insights and yield an in vivo ratio of
      attached and free membrane areas without cell fixation. As an example, glass
      substrates were modified with different proteins (fibronectin, laminin,
      concavalin A, extracellular matrix gel, and both isomers of poly-lysine) and
      presented to HEK293 cells to examine differences in cell morphology and adhesion.
      We proved that proteins on a substrate could increase the attached portion of a
      cell membrane, facing the modified substrate, from an average of 32% (glass) to
      45% (poly-lysine) of the total membrane surface area.

PMID- 18621416
TI  - Gemtuzumab-ozogamicin in combination with fludarabine, cytarabine, idarubicin
      (FLAI-GO) as induction therapy in CD33-positive AML patients younger than 65
      years.
AB  - INTRODUCTION: The addition of gemtuzumab-ozogamicin (GO) to an induction regimen
      including synergistic drugs, such as intermediate dose of cytarabine (Ara-C),
      idarubicin and fludarabine (FLAI), could reduce treatment failure in acute
      myeloid leukemia (AML) patients. Nevertheless, the role and safety of this
      antibody target-therapy in first-line chemotherapy in patients younger than 65
      years has not yet been defined. PATIENTS AND METHODS: The primary goal of this
      prospective phase II pilot study was to evaluate the efficacy and the safety
      profile of FLAI plus GO as induction regimen. Thirty consecutive AML patients
      were included. All patients were younger than 65 with a median age of 53 years
      and CD33 expression exceeded 20% in all cases. The M/F ratio was 16/14 and 21/30
      (70%) of patients were poor-risk at diagnosis. The induction regimen (FLAI-GO)
      included fludarabine (30mg/m(2)) and Ara-C (2g/m(2)) on days 1-5, idarubicin
      (10mg/m(2)) on days 1, 3, and 5 and GO (3mg/m(2)) on day 6. Hematopoietic stem
      cell transplant (HSCT) was planned for all high risk AML patients in first
      complete remission (CR) after consolidation with intermediate doses of Ara-C and
      idarubicin (IDAC-IDA). Cytogenetic, multidrug-resistance phenotype, FLT3 mutation
      status, and WT1 quantitative expression analyses were performed at diagnosis in
      all patients. WT1 expression and cytogenetic (in positive cases) analyses were
      performed after induction to detect and follow minimal residual disease. RESULTS:
      Patients were evaluated for response rate, treatment-related adverse events,
      overall survival and relapse free survival. After induction with FLAI-GO, CR rate
      was 90% (26 of 29 evaluable pts); one patient achieved partial remission and two
      were resistant. There was only one case of death during induction (DDI). After
      FLAI-GO, the mean value of WT1 dropped from 4200+/-2777 copies/10(4)ABL to 192+/
      399 copies/10(4)ABL. The toxicity of FLAI-GO was acceptable; 57% of patients
      experienced transient and reversible GO infusion-related adverse events
      (especially fever and chills), but no cases of veno-occlusive disease occurred
      during CHT or after HSCT. After a median follow-up of 16 months (range 2-25),
      24/30 (80%) patients are alive (24/24 in CR). The probability of 1-year OS and
      RFS was 90 and 85%, respectively. Allogeneic and autologus HSCT was performed in
      19 (63%) and 4 (13%) patients, respectively. CONCLUSIONS: These preliminary
      results suggest that FLAI-GO is an effective and well tolerated induction regimen
      for CD33 positive AML patients younger than 65 years, with a high complete
      response rate, favourable safety profile, low DDI. These results encourage the
      testing of this regimen in a multicenter prospective trial.

PMID- 18621417
TI  - Inhibition of the mevalonate pathway potentiates the effects of lenalidomide in
      myeloma.
AB  - The effects of the combination of simvastatin and lenalidomide were analyzed in
      myeloma. Myeloma cell lines and patient myeloma cells were incubated with
      different concentrations of lenalidomide, simvastatin, or the combination. Co
      exposure to simvastatin and lenalidomide resulted in a synergistic reduction of
      cell viability in myeloma cells. This effect was due to induction of apoptosis
      and inhibition of proliferation. The combination augmented induction of caspase-8
      cleavage and enhanced down-regulation of pStat3. Mevalonate and GGOH abrogated
      the synergy between lenalidomide and simvastatin. These data provide a rationale
      for the clinical evaluation of lenalidomide and simvastatin in patients with
      myeloma.

PMID- 18621418
TI  - Resistance to amoebic gill disease (AGD) is characterised by the transcriptional
      dysregulation of immune and cell cycle pathways.
AB  - Amoebic gill disease (AGD) is a parasite-mediated proliferative gill disease
      capable of affecting a range of teleost hosts. While a moderate heritability for
      AGD resistance in Atlantic salmon has been reported previously, the mechanisms by
      which individuals resist the proliferative effects remain poorly understood. To
      gain more knowledge of this commercially important trait, we compared gill
      transcriptomes of two groups of Atlantic salmon, one designated putatively
      resistant, and one designated putatively susceptible to AGD. Utilising a 17k
      Atlantic salmon cDNA microarray we identified 196 transcripts that were
      differentially expressed between the two groups. Expression of 11 transcripts
      were further examined with real-time quantitative RT-PCR (qPCR) in the AGD
      resistant and AGD-susceptible animals, as well as non-infected naive fish. Gene
      expression determined by qPCR was in strong agreement with the microarray
      analysis. A large number of differentially expressed genes were involved in
      immune and cell cycle responses. Resistant individuals displayed significantly
      higher expression of genes involved in adaptive immunity and negative regulation
      of the cell cycle. In contrast, AGD-susceptible individuals showed higher
      expression of acute phase proteins and positive regulators of the cell cycle.
      Combined with the gill histopathology, our results suggest AGD resistance is
      acquired rather than innately present, and that this resistance is for the most
      part associated with the dysregulation of immune and cell cycle pathways.

PMID- 18621420
TI  - Bradykinin-induced IL-6 expression through bradykinin B2 receptor, phospholipase
      C, protein kinase Cdelta and NF-kappaB pathway in human synovial fibroblasts.
AB  - Bradykinin (BK) is an inflammatory mediator, and shows elevated levels in regions
      of severe injury and inflammatory diseases. It has been shown to induce
      interleukin-6 (IL-6) expression in inflammatory responses in rheumatoid
      arthritis. We investigated the signaling pathway involved in IL-6 production
      caused by BK in synovial fibroblasts. BK caused concentration- and time-dependent
      increases in IL-6 production. By using pharmacological inhibitors or genetic
      inhibition of the BK receptor, siRNA revealed that B2 but not B1 BK receptors are
      involved in BK-mediated up-regulation of IL-6. BK-mediated IL-6 production was
      attenuated by phospholipase C inhibitor (U73122), protein kinase Cdelta inhibitor
      (rottlerin), NF-kappaB inhibitor (PDTC), IkappaB protease inhibitor (TPCK) and NF
      kappaB inhibitor peptide. Stimulation of synovial fibroblasts with BK activated
      IkappaB kinase alpha/beta (IKK alpha/beta), IkappaBalpha phosphorylation,
      IkappaBalpha degradation, p65 phosphorylation at Ser(276), p65 and p50
      translocation from the cytosol to the nucleus and kappaB-luciferase activity. BK
      mediated an increase of IKK alpha/beta and IkappaBalpha phosphorylation, kappaB
      luciferase activity and p65 and p50 binding to the NF-kappaB element was
      inhibited by B2 BK receptor antagonist (HOE140), U73122 and rottlerin. Our
      results suggest that BK increased IL-6 production in synovial fibroblasts via the
      B2 BK receptor/PI-PLC/PKCdelta/and NF-kappaB signaling pathway.

PMID- 18621419
TI  - Comprehensive 3D-modeling of allergenic proteins and amino acid composition of
      potential conformational IgE epitopes.
AB  - Similarities in sequences and 3D structures of allergenic proteins provide vital
      clues to identify clinically relevant immunoglobulin E (IgE) cross-reactivities.
      However, experimental 3D structures are available in the Protein Data Bank for
      only 5% (45/829) of all allergens catalogued in the Structural Database of
      Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP). Here, an automated
      procedure was used to prepare 3D-models of all allergens where there was no
      experimentally determined 3D structure or high identity (95%) to another protein
      of known 3D structure. After a final selection by quality criteria, 433 reliable
      3D models were retained and are available from our SDAP Website. The new 3D
      models extensively enhance our knowledge of allergen structures. As an example of
      their use, experimentally derived "continuous IgE epitopes" were mapped on 3
      experimentally determined structures and 13 of our 3D-models of allergenic
      proteins. Large portions of these continuous sequences are not entirely on the
      surface and therefore cannot interact with IgE or other proteins. Only the
      surface exposed residues are constituents of "conformational IgE epitopes" which
      are not in all cases continuous in sequence. The surface exposed parts of the
      experimental determined continuous IgE epitopes showed a distinct statistical
      distribution as compared to their presence in typical protein-protein interfaces.
      The amino acids Ala, Ser, Asn, Gly and particularly Lys have a high propensity to
      occur in IgE binding sites. The 3D-models will facilitate further analysis of the
      common properties of IgE binding sites of allergenic proteins.

PMID- 18621421
TI  - Mononuclear metal complexes with ciprofloxacin: Synthesis, characterization and
      DNA-binding properties.
AB  - Five novel metal complexes of the quinolone antibacterial agent ciprofloxacin
      with Mn(2+), Fe(3+), Co(2+), Ni(2+) and MoO(2)(2+) have been prepared and
      characterized with physicochemical, spectroscopic and electrochemical techniques.
      In all these complexes, ciprofloxacin acts as a bidentate deprotonated ligand
      bound to the metal through the pyridone oxygen and one carboxylate oxygen. The
      central metal in each complex is six-coordinate and a slightly distorted
      octahedral geometry is proposed. The lowest energy model structures of the
      Mn(2+), Fe(3+) and MoO(2)(2+) complexes have been determined with molecular
      modeling calculations. The cyclic voltammograms of the complexes have been
      recorded in dmso solution and in 1/2 dmso/buffer (containing 150mM NaCl and 15mM
      trisodium citrate at pH 7.0) solution and the corresponding redox potentials have
      been estimated. The biological activity of the complexes has been evaluated by
      examining their ability to bind to calf-thymus DNA (CT DNA) with UV and
      fluorescence spectroscopies and cyclic voltammetry. UV studies of the interaction
      of the complexes with DNA have shown that these compounds can bind to CT DNA. The
      binding constants of the complexes with CT DNA have also been calculated. The
      cyclic voltammograms of the complexes in the presence of CT DNA have shown that
      the complexes can bind to CT DNA by both the intercalative and the electrostatic
      binding mode. Competitive studies with ethidium bromide (EB) have shown that the
      complexes exhibit the ability to displace the DNA-bound EB indicating that the
      complexes bind to DNA probably via intercalation in strong competition with EB
      for the intercalative binding site.

PMID- 18621422
TI  - The response of HEK293 cells transfected with bovine TLR2 to established pathogen
      associated molecular patterns and to bacteria causing mastitis in cattle.
AB  - Toll-like receptors (TLRs) are key sensors of pathogen-associated molecular
      patterns (PAMPs). Their role in immunity is difficult to examine in species of
      veterinary interest, due to restricted access to the knockout technology and TLR
      specific antibodies. An alternative approach is to generate cell lines
      transfected with various TLRs and to examine the recognition of PAMPs or relevant
      bacteria. In this report, we examined whether recognition of various PAMPs and
      mastitis-causing bacteria is achieved by transfection of recombinant bovine TLR2
      (boTLR2). Therefore, human embryonic kidney (HEK) 293 cells were transfected by
      whole boTLR2. A clonal analysis of stably transfected cells disclosed variable
      recognition of several putative TLR2 agonists although expressing similar amounts
      of the transgene and endogenous TLR6. One clone (clone 25) reacted by copious
      interleukin-8 (IL-8) production to several stimulants of TLR2 such as di
      palmitoylated cysteyl-seryl-lysyl-lysyl-lysyl-lysine (Pam2), a biochemical
      preparation of lipoteichoic acid from Staphylococcus aureus, a commercial
      preparation of peptidoglycan from S. aureus, and heat-killed Listeria
      monocytogenes (HKLM). TLR2-dependent induction of IL-8 release was stronger in
      medium containing human serum albumin than in medium containing fetal calf serum.
      Clone 25 cells responded to high concentrations of S. aureus and to Escherichia
      coli causing mastitis, but not to Streptococcus uberis and to Streptococcus
      agalactiae which also cause mastitis. Stimulation by S. aureus was relatively
      weak when compared (i) with stimulation of the same cells by HKLM and PAMPs
      derived from S. aureus, (ii) with a clone stably transfected with TLR4 and MD-2
      and stimulated by E. coli causing mastitis, and (iii) with interferon-gamma
      costimulated bovine macrophages stimulated by S. aureus and S. agalactiae. Thus,
      clone 25 is suitable for studying the interaction of putative TLR2 agonists with
      bovine TLR2-transfected cells, provides a cell to search for TLR2-specific
      antibodies, and is a tool for studying the interaction of TLR2 with bacteria
      causing disease, e.g. mastitis, in cattle.

PMID- 18621423
TI  - Immunopathological mechanisms in dogs with rupture of the cranial cruciate
      ligament.
AB  - The majority of studies on cranial cruciate ligament (CrCL) disease to date have
      been carried out on dogs that already sustained a CrCL rupture, which is the end
      stage of the disease. Investigations have recently been carried out to study
      humoral and cellular immunopathological mechanisms in predisposed dogs before
      clinical rupture of the contralateral CrCL. The cruciate ligaments are mainly
      composed of collagen type I, and immune responses to collagen have been suggested
      as a cause of CrCL degradation in dogs. None of these investigations showed
      evidence that anticollagen type I antibodies alone initiate CrCL damage. However,
      in predisposed dogs a distinct anticollagen type I antibody gradient was found
      towards the contralateral stifle joint that eventually sustained a CrCL rupture,
      suggesting that there was an inflammatory process present in these joints before
      detectable joint instability occurred. The importance of cellular reactivity to
      collagen type I in cruciate disease also remains unclear. Peripheral blood
      mononuclear cell proliferation to collagen type I was very diverse in dogs with
      cruciate disease whereas some sham operated dogs and healthy dogs tested positive
      as well. It is not yet determined whether cellular reactivity to collagen type I
      exists locally in the stifle joints nor whether this could initiate CrCL
      degradation. Inflammatory processes within the stifle joint can alter the
      composition of the cruciate ligaments. In animal models of immune-mediated
      synovitis, the mechanical strength of the CrCL is significantly reduced.
      Immunohistochemical studies on synovial tissues from dogs with rheumatoid
      arthritis and dogs with cruciate disease revealed that the pathologic features
      are similar in both joint pathologies and that the differences are mainly
      quantitative. Joint inflammation induced by biochemical factors such as cytokines
      has been implied in CrCL degeneration. In several studies, the levels of pro
      inflammatory and T helper cytokines were measured in dogs that sustained a CrCL
      rupture, but the exact role of the various cytokines in the pathogenesis of CrCL
      disease remains inconclusive. More recently, the levels of the cytokines have
      been investigated over time in predisposed dogs before and after CrCL rupture. IL
      8 expression tended to be higher in stifle joints that will rupture their CrCL
      during the next 6 months than in those that will not, indicating an inflammatory
      process in these joints before clinical rupture. This review provides a
      comprehensive overview of all possible implications of humoral and cell-mediated
      immune responses published in dogs with cruciate disease together with
      publications from human joint diseases. Furthermore, this review highlights
      recent findings on cytokines and proteinases in the accompanying joint
      inflammation.

PMID- 18621424
TI  - A role for membrane potential in regulating GPCRs?
AB  - G-protein-coupled receptors (GPCRs) have ubiquitous roles in transducing
      extracellular signals into cellular responses. Therefore, the concept that
      members of this superfamily of surface proteins are directly modulated by changes
      in membrane voltage could have widespread consequences for cell signalling.
      Although several studies have indicated that GPCRs can be voltage dependent,
      particularly P2Y(1) receptors in the non-excitable megakaryocyte, the evidence
      has been mostly indirect. Recent work on muscarinic receptors has stimulated
      substantial interest in this field by reporting the first voltage-dependent
      charge movements for a GPCR. An underlying mechanism is proposed whereby a
      voltage-induced conformational change in the receptor alters its ability to
      couple to the G protein and thereby influences its affinity for an agonist. We
      discuss the strength of the evidence behind this hypothesis and include
      suggestions for future work. We also describe other examples in which direct
      voltage control of GPCRs can account for effects of membrane potential on
      downstream signals and highlight the possible physiological consequences of this
      phenomenon.

PMID- 18621426
TI  - Influence of cognition on personal activities of daily living (P-ADL) in the
      acute phase: the Gothenburg Cognitive Stroke Study in Elderly.
AB  - This study examines how prestroke dementia and cognitive dysfunction after stroke
      influence the personal activities of daily living (P-ADL) in elderly patients in
      the acute phase after stroke. Elderly stroke patients (n=60) referred to
      geriatric rehabilitation were included. Assessments were carried out at admission
      and evaluated at discharge from the geriatric ward. The median age of the group
      was 77 years. Astrand's questionnaire was used to interview a close relative
      about the patient's prestroke cognitive status. P-ADL was assessed with the
      Barthel Index (BI). The Mini Mental State Examination (MMSE) and a
      neuropsychological test battery were used to measure cognitive functions.
      Analyses were made using non-parametrical methods. In the acute phase after
      stroke, neither the presence of prestroke dementia nor the cognitive status after
      stroke onset among these elderly patients influenced P-ADL at admission or at
      discharge. Prestroke dementia and cognitive dysfunction's were found to be common
      after stroke onset, however this did not have any impact on dependence in P-ADL
      in these elderly patients at admission or at discharge.

PMID- 18621425
TI  - Identification of polymerase and processivity inhibitors of vaccinia DNA
      synthesis using a stepwise screening approach.
AB  - Nearly all DNA polymerases require processivity factors to ensure continuous
      incorporation of nucleotides. Processivity factors are specific for their cognate
      DNA polymerases. For this reason, the vaccinia DNA polymerase (E9) and the
      proteins associated with processivity (A20 and D4) are excellent therapeutic
      targets. In this study, we show the utility of stepwise rapid plate assays that
      (i) screen for compounds that block vaccinia DNA synthesis, (ii) eliminate
      trivial inhibitors, e.g. DNA intercalators, and (iii) distinguish whether
      inhibitors are specific for blocking DNA polymerase activity or processivity. The
      sequential plate screening of 2222 compounds from the NCI Diversity Set library
      yielded a DNA polymerase inhibitor (NSC 55636) and a processivity inhibitor (NSC
      123526) that were capable of reducing vaccinia viral plaques with minimal
      cellular cytotoxicity. These compounds are predicted to block cellular infection
      by the smallpox virus, variola, based on the very high sequence identity between
      A20, D4 and E9 of vaccinia and the corresponding proteins of variola.

PMID- 18621427
TI  - Predicting health behaviors with an experimental measure of risk preference.
AB  - We conduct a large-scale economics experiment paired with a survey to examine the
      association between individual risk preference and health-related behaviors among
      adults aged 18-87 years. Risk preference is measured by the lottery choice
      experiment designed by Holt and Laury [Holt, C.A., Laury, S.K., 2002. Risk
      aversion and incentive effects. The American Economic Review 92(5), 1644-1655].
      Controlling for subject demographic and economic characteristics, we find that
      risk aversion is negatively and significantly associated with cigarette smoking,
      heavy drinking, being overweight or obese, and seat belt non-use. In additional
      specifications, we find that risk aversion is negatively and significantly
      associated with the likelihood a subject engaged in any of five risky behaviors
      and the number of risky behaviors reported.

PMID- 18621428
TI  - Long-term results of a prospective multicenter phase II study to preserve the
      larynx function using concomitant boost radiochemotherapy with Carboplatin.
AB  - PURPOSE: This prospective phase II study was undertaken to assess the feasibility
      of a larynx preservation protocol with simultaneous radiochemotherapy. PATIENTS
      AND METHODS: Between 3/1998 and 10/2000, 42 patients with moderately advanced
      cancer of the larynx (n=25) and hypopharynx (n=17) eligible for total
      laryngectomy (LE) were treated in a prospective larynx preservation study. The
      study protocol scheduled 66Gy in 5 weeks using a concomitant boost technique and
      70mg/m(2) Carboplatin on days 1-5 in weeks 1 and 5. RESULTS: The median follow-up
      time of the censored study patients was 41 months (9-95 months). The 5-year
      overall survival was 0.66 (95% CI 0.48-0.84), the 5-year laryngectomy-free
      survival 0.60 (95% CI 0.42-0.78), and the laryngeal preservation rate at 5 years
      0.67 (95% CI 0.49-0.85). Cox multivariate regression analysis showed the total
      tumor volume to be the only statistically significant factor on locoregional
      failure-free survival. Six of 23 tumor-free long-term survivors received a
      tracheotomy because of late laryngeal toxicity associated with dysphagia 30-79
      months after radiochemotherapy. CONCLUSIONS: Due to the late laryngeal toxicity
      observed the value of this regimen for larynx preservation is limited.

PMID- 18621429
TI  - Cost-effectiveness of screening and correcting refractive errors in school
      children in Africa, Asia, America and Europe.
AB  - OBJECTIVE: To estimate the costs and effects of alternative strategies for annual
      screening of school children for refractive errors, and the provision of
      spectacles, in different WHO sub-regions in Africa, Asia, America and Europe.
      METHODS: We developed a mathematical simulation model for uncorrected refractive
      error, using prevailing prevalence and incidence rates. Remission rates reflected
      the absence or presence of screening strategies for school children. All
      screening strategies were implemented for a period of 10 years and were compared
      to a situation were no screening was implemented. Outcome measures were life
      years adjusted for disability (DALYs), costs of screening and provision of
      spectacles and follow-up for six different screening strategies, and cost
      effectiveness in international dollars per DALY averted. Epidemiological
      information was derived from the burden of disease study from the World Health
      Organization (WHO). Cost data were derived from large databases from the WHO.
      Both univariate and multivariate sensitivity analyses were performed on key
      parameters to determine the robustness of the model results. RESULTS: In all
      regions, screening of 5-15 years old children yields most health effects,
      followed by screening of 11-15 years old, 5-10 years old, and screening of 8 and
      13 years old. Screening of broad-age intervals is always more costly than
      screening of single-age intervals, and there are important economies of scale for
      simultaneous screening of both 5-10 and 11-15-year-old children. In all regions,
      screening of 11-15 years old is the most cost-effective intervention, with the
      cost per DALY averted ranging from I$67 per DALY averted in the Asian sub-region
      to I$458 per DALY averted in the European sub-region. The incremental cost per
      DALY averted of screening 5-15 years old ranges between I$111 in the Asian sub
      region to I$672 in the European sub-region. CONCLUSIONS: Considering the
      conservative study assumptions and the robustness of study conclusions towards
      changes in these assumptions, screening of school children for refractive error
      is economically attractive in all regions in the world.

PMID- 18621430
TI  - Smoke-free restaurants in Shanghai: should it be mandatory and is it acceptable?
AB  - OBJECTIVES: This study aims to describe secondhand smoke (SHS) exposure in
      restaurants in Shanghai and to explore the impact on the health of restaurant
      workers. Attitude to smoke-free restaurants among restaurant workers and
      customers was also determined in this study. METHODS: A random sample of 242
      workers, 284 customers, and 46 restaurant owners participated in face-to-face
      questionnaire interviews. RESULTS: A total of 219 (90.7%) restaurant workers
      surveyed were found to be exposed to SHS during working hours with 24.2+/-18.6h
      of exposure on average per week. Exposure time each week was significantly
      associated with the symptoms of dyspnea and irritated eyes. Among the customers
      surveyed 73.9% supported the concept of a 100% smoke-free law in restaurants and
      49.6% expressed that they would be more likely to eat in restaurants if smoking
      was banned in restaurants. And 58.6% of the restaurant owners surveyed regarded
      smoke-free laws banning smoking in restaurant as feasible and 56.5% estimated
      such bans would decrease the profit. CONCLUSION: Both restaurant workers and
      customers are substantially exposed to SHS. Although some restaurant owners are
      concerned about a decrease in profits, the fear of losing business is not
      supported by the response among customers. Therefore, introducing a law-banning
      smoking in restaurants appears to be feasible and acceptable in Shanghai.

PMID- 18621431
TI  - Formal interaction specification in public health surveillance systems using pi
      calculus.
AB  - This paper provides formal specification of interactions in typical public health
      surveillance systems involving healthcare agencies at local, state and federal
      levels. Although few standards exist for exchange of healthcare information,
      there is a general lack of formal models of the protocols involved in the
      interactions between the agencies. The quality of medical care provided is an end
      result of a well designed choreography of diverse services provided by different
      healthcare entities. One of the major challenges in this field appears to be
      explicit formal specification of such interactions. Such formal specification
      work is the first step leading to both design and verification of important
      properties of public healthcare systems. pi-calculus is a formal modeling
      technique for precise specification of semantics in interacting concurrent
      systems where mobility is involved. Two different configurations of public health
      surveillance systems are modelled using pi-calculus in this paper.

PMID- 18621432
TI  - Systemic chemotherapy after cranial irradiation in patients with brain metastases
      from non-small cell lung cancer: a retrospective study.
AB  - BACKGROUND: Brain metastases (BMs) are found in about 10% of patients with newly
      diagnosed non-small cell lung cancer (NSCLC). This retrospective study was
      conducted to assess the clinical outcomes and prognostic factors of patients who
      received chemotherapy after cranial irradiation for NSCLC with synchronous BMs.
      MATERIALS AND METHODS: From January 2000 through July 2007, we reviewed the
      medical records of patients who received systemic chemotherapy following cranial
      irradiation for BMs from newly diagnosed NSCLC. RESULTS: A total of 40 patients
      were included in this review. As the first-line chemotherapy, a total of 114
      cycles were administered, for a median number of 2 cycles per patient (range, 0.5
      8 cycles). Thirty-four patients (85%) received platinum-based combination regimen
      and the remaining 6 received chemotherapy with a single agent. Sixteen (40%)
      patients, 11 of whom had ECOG of 2, only received 1 cycle or less of chemotherapy
      due to early death, rapid progression, clinical impairment, or toxicity. For 28
      patients who were evaluable for response, the extracranial overall response rate
      was 43%. The median overall survival for all patients was 7 months (range, 0.9
      25.3 months) and an estimated 1-year survival rate was 23%. Multivariate analysis
      revealed that ECOG status (P=0.018) and number of BM (P=0.038) were independent
      prognostic factors. CONCLUSION: Our results suggest that chemotherapy can be used
      to increase survival of patients treated with cranial irradiation for newly
      diagnosed NSCLC with synchronous BM. However, systemic chemotherapy should be
      carefully considered according to the patient's prognostic condition. Especially,
      patients with good performance status and limited number of BM may be good
      candidates for systemic chemotherapy after cranial irradiation.

PMID- 18621433
TI  - The oligomeric status of syndecan-4 regulates syndecan-4 interaction with alpha
      actinin.
AB  - Syndecan-4, a cell surface heparan sulfate proteoglycan, is known to regulate the
      organization of the cytoskeleton, and oligomerization is crucial for syndecan-4
      function. We therefore explored a possible regulatory effect of syndecan-4
      oligomerization on the cytoskeleton. Glutathione-S-transferase-syndecan-4
      proteins were used to show that syndecan-4 interacted specifically with alpha
      actinin, but not paxillin, talin, and vinculin. Interestingly, only dimeric, and
      not monomeric, recombinant syndecan-4 interacted with alpha-actinin in the
      presence of phosphatidylinositol 4,5-bisphosphate (PIP2), and PIP2 potentiated
      the interaction of both the cytoplasmic domain syndecan-4 peptide and recombinant
      syndecan-4 proteins with alpha-actinin, implying that oligomerization of syndecan
      4 was important for this interaction. Consistent with this notion, alpha-actinin
      interaction was largely absent in syndecan-4 mutants defective in transmembrane
      domain-induced oligomerization, and alpha-actinin-associated focal adhesions were
      decreased in rat embryo fibroblasts expressing mutant syndecan-4. Besides, this
      interaction was consistently lower with the phosphorylation-mimicking syndecan-4
      mutant S183E which is known to destabilize the oligomerization of the syndecan-4
      cytoplasmic domain. Taken together, the data suggest that the oligomeric status
      of syndecan-4 plays a crucial role in regulating the interaction of syndecan-4
      with alpha-actinin.

PMID- 18621434
TI  - Environmental meticillin-resistant Staphylococcus aureus (MRSA) disinfection
      using dry-mist-generated hydrogen peroxide.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) is a major problem in hospitals
      worldwide. Hand hygiene is recognised as crucial in limiting the spread of MRSA
      but less is known about the role of MRSA reservoirs in the inanimate hospital
      environment. We evaluated the effect of hydrogen peroxide vapour diffused by
      Sterinis((R)) against MRSA in two experimental hospital settings and in two field
      trials. Dipslides were used for MRSA detection and quantification before and
      after using the Sterinis disinfection process. In the first experimental hospital
      setting, four epidemic MRSA strains were placed at five locations and left for
      one week. All strains survived the week but not the disinfection process. In
      field trial one 14 upholstered chairs from a department with many MRSA positive
      patients were left for one month in a closed room prior to disinfection. MRSA was
      found on the upholstery of four of the 14 chairs. Three chairs became MRSA
      negative immediately after the disinfection, the fourth 24h later. The second
      field trial was in the private home of a MRSA positive family of four
      individuals. One location was found MRSA positive, remaining so after the
      Sterinis cycles. We found Sterinis to be effective against MRSA in the
      experimental hospital setting and upholstered chairs, but not in the private home
      of heavily colonised MRSA patients.

PMID- 18621435
TI  - Are lanyards a risk for nosocomial transmission of potentially pathogenic
      bacteria?

PMID- 18621436
TI  - Surgical site infections in cardiac surgery after a hospital catastrophe.
AB  - On 2 November 1999, one of the main hospital facades adjoining cardiovascular
      surgery collapsed in a 900-bed teaching hospital in Santander, Spain. The purpose
      of this study was to determine whether the accident affected the safety of
      patients by increasing the risk for nosocomial and surgical site infections
      (SSI). Measures for the prevention of nosocomial infections were immediately
      reinforced. A total of 217 consecutive patients were operated on before 2
      November 1999, with another 296 after this date. Patients in both study periods
      showed similar severity of illness, complexity of surgical procedure and length
      of hospital stay. The overall rate of nosocomial infection before and after the
      accident was 28.1% and 24.7%, respectively (P=0.381). The rates of respiratory
      infection, urinary infection and bacteraemia were also similar. A statistically
      significant reduction in the SSI rate in the second period was observed (14.8% vs
      4.4%, P=0.008). The collapse of the facade was not associated with any increase
      in nosocomial infection rates, but there was a significant reduction of SSI rates
      in relation to intensive infection control measures implemented after the
      collapse.

PMID- 18621437
TI  - Investigation and management of an outbreak of mucormycosis in a paediatric
      oncology unit.
AB  - Mucormycosis is an aggressive and often fatal infection, despite conventional
      methods of treatment, which predominantly affects immunocompromised patients.
      This report describes an outbreak of rhinocerebral mucormycosis in a university
      hospital paediatric oncology department secondary to water damage in a linen
      store and parents' shower room. The source of the outbreak was successfully
      determined using simple environmental sampling techniques. Sampling allowed
      timely and successful implementation of infection control measures to contain the
      source and protect patients. Two cases were treated with posaconazole and made a
      complete recovery, with no discernible impact on the management of their cancer.
      Fifteen other children identified as having a high risk of developing infection
      were given posaconazole prophylaxis. None of the children, including one that was
      only five years old, experienced any adverse events from taking posaconazole.

PMID- 18621438
TI  - Audience readings of media messages about MRSA.
AB  - This paper explores whether, and to what extent, national newspaper messages
      tally with public perceptions about meticillin-resistant Staphylococcus aureus
      (MRSA). It compares research on media messages about MRSA with interview data
      gathered from a demographically diverse sample of 60 people interviewed from the
      Greater London area. Across the interview sample there was a shared consensus
      that most people associated MRSA not with the history of antibiotic use, but with
      dirty and poorly managed hospitals. Some media messages, such as blaming MRSA on
      the alleged 'management culture' of the NHS, seemed to capture the Zeitgeist,
      whereas others, in particular the 'celebrity victims' of MRSA, did not seem to
      resonate with the audience. This study also found that ideas based on scientific
      understandings about germ theory and the immune system were held alongside
      folklore such as miasmic theory. The comparison of media and mind thus points to
      the existence of pre-scientific understandings of germs, contagion and blame in
      parallel with the biomedical story in the minds of the public. The findings
      contribute to our understanding of the public and patients' views of this
      infection.

PMID- 18621440
TI  - Risk factors associated with mortality of infections caused by Stenotrophomonas
      maltophilia: a systematic review.
AB  - The objective of this review was to assess the quality of available literature
      regarding risk factors associated with mortality of infections caused by S.
      maltophilia. PubMed and OVID were searched from March 1985 to March 2008, and
      eligible studies were considered to be those that related S. maltophilia
      infection with risk factors associated with mortality; described the
      characteristics of patients in detail; and provided data regarding the outcome
      and mortality. Thirty-eight studies were found referring to S. maltophilia (four
      with multivariate analysis and 10 with univariate analysis). This review has
      several limitations, mainly due to the heterogeneity of patients, lack of
      appropriate statistical analysis and lack of definition of nosocomial and
      community infection studies. Data reviewed suggest that infections caused by S.
      maltophilia have high mortality and that the risk factors associated with
      mortality are related to the initial clinical condition and patient type.
      Underlying haematological disease in cancer patients and admission to the
      intensive care unit are independent risk factors associated with mortality.
      Shock, thrombocytopenia and Acute Physiological Assessment and Chronic Health
      Evaluation (APACHE) score >15 are independent risk factors associated with
      outcome in patients with bloodstream infection and pneumonia. Organ dysfunction
      is the only independent risk factor associated with death from infection caused
      by sulfamethoxazole-resistant S. maltophilia. The impact of adequate
      antimicrobial therapy and removal of central venous catheter on mortality require
      further clinical studies.

PMID- 18621441
TI  - Infection controls: the hospital bed-control handset.

PMID- 18621442
TI  - Single-dose cefuroxime with gentamicin reduces Clostridium difficile-associated
      disease in hip-fracture patients.
AB  - Antibiotic-associated Clostridium difficile diarrhoea may complicate recovery
      from surgery for proximal femoral fracture. We undertook a four-year case-control
      study to evaluate a change in antibiotic prophylaxis in our department. During
      the period January 2003 to January 2005, patients received three doses of
      prophylactic cefuroxime (1.5g). We then introduced a new regimen, comprising of
      one single dose of cefuroxime (1.5g) with gentamicin (240mg) at induction. Prior
      to the change in prophylaxis, 912 patients underwent surgery for neck of femur
      fracture, and from March 2005 to March 2007, 899 patients had surgery under the
      new regimen. Thirty-eight patients developed C. difficile infection (4.2%) in the
      initial group, compared with 14 patients (1.6%) in the group with the new regimen
      (P=0.009). The incidence of C. difficile infection increased throughout the rest
      of the hospital over the same time period. Patients with C. difficile infection
      had a statistically significant increase in antibiotic exposure, inpatient stay,
      morbidity and inpatient mortality. The main challenges regarding prophylactic
      antibiotic selection are infection due to meticillin-resistant Staphylococcus
      aureus (MRSA) and C. difficile-associated diarrhoea. We advocate the use of the
      new regimen as an alternative to multiple-dose cephalosporin antibiotics for the
      prevention of C. difficile infection in this group of high-risk patients.

PMID- 18621443
TI  - Obligatory occupational health check increases vaccination rates among medical
      students.
AB  - In October 2002 an obligatory occupational health check for all preclinical
      students at the University of Erlangen-Nuremberg was introduced. Over the period
      2005 to 2007, medical students started their clinical year either with or without
      a health check during their preclinical years. The aim of the study was to
      evaluate the efficacy of health checks for preclinical students with respect to
      vaccination rates. At the beginning of the clinical year we examined 242
      consecutive students, 121 with and 121 without a preceding preclinical
      occupational health check. The immunisation rate against hepatitis B increased
      during medical education from 50% to 96% in women and from 58% to 96% in men. In
      medical students without an initial occupational health check, vaccination rates
      were significantly lower (85% in women and 81% in men). A significant benefit
      from the preclinical check was seen in men regarding immunisation status for
      hepatitis B, tetanus, diphtheria, polio, rubella and mumps and in women for
      hepatitis B and rubella. This study demonstrates that it is possible to
      significantly increase vaccination rates, particularly for men. Even in medical
      students starting their clinical training, an individual occupational health
      check is necessary to optimise immunisation against infectious diseases. Routine
      occupational health checks could make an important contribution to closing gaps
      in vaccination coverage.

PMID- 18621444
TI  - Community-acquired norovirus diarrhoea outbreak mimicking a community-acquired C.
      difficile diarrhoea outbreak.

PMID- 18621445
TI  - Investigation and control of a cluster of penicillin non-susceptible
      Streptococcus pneumoniae infections in a care home.
AB  - Two elderly residents of a care home were hospitalised with pneumonia over a
      period of one month. They had bacteraemia with penicillin non-susceptible
      Streptococcus pneumoniae (PNSP) and both died. All residents and staff of the
      care home were screened for PNSP using nasopharyngeal swabs, with one resident
      and one member of staff found to be asymptomatic carriers. Oral rifampicin was
      given to the carriers. All four strains were found to be serotype 14, and
      multilocus sequence typing (MLST) showed ST2652, not previously detected in
      Scotland. Review of care home residents showed that pneumococcal vaccination
      coverage was low (63%). This is similar to rates found in those aged > or =65
      years in the general population and needs to be improved upon.

PMID- 18621446
TI  - Pyjamas and sheets as a potential source of nosocomial pathogens.

PMID- 18621448
TI  - Synthesis, characterization and antidiabetic properties of N(1)-2,4
      dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato
      oxovanadium(IV).
AB  - A new oxovanadium(IV) chelate [VOL] (L: N(1)-2,4-dihydroxybenzylidene-N(4)-2
      hydroxybenzylidene-S-methyl-thiosemicarbazidato) was synthesized and
      characterized by elemental analysis, conductivity and magnetic measurements, UV
      vis, IR, EPR spectroscopy and mass spectrometry. The biochemical and
      immunohistochemical effects of the administration of the vanadium complex (VOL)
      into the pancreas of normal and streptozotocin-induced diabetic rats were
      profoundly investigated. The animals were randomly divided into four groups.
      Group I: control (intact) animals. Group II: control animals administered with
      VOL. Group III: STZ-induced diabetic animals. Group IV: STZ-induced diabetic
      animals administered with VOL. VOL was given to some of the experimental animals
      by gavage at a dose of 0.2mM/kg every day for 12 days. Blood samples were
      collected from animals, on 0 and 1, 6 and 12 days after STZ injection. On day 12,
      the pancreatic tissues were taken from the animals. The tissue sections were
      labelled with streptavidin biotin peroxidase technique for insulin. In the
      diabetic group, the blood glucose levels, aspartate and alanine transaminases,
      alkaline phosphatase activities were increased. But, in the diabetic+VOL groups,
      the blood glucose levels, aspartate and alanine transaminases, alkaline
      phosphatase activities were reduced. In the diabetic group, a decrease in the
      pancreatic glutathione levels, glutathione peroxidase and superoxide dismutase
      activities and an increase in the pancreatic lipid peroxidation level and
      catalase activities were observed. The administration of VOL to the diabetic rats
      reversed this diabetic effect due to its insulinomimetic effects. According to
      the immunohistochemical and biochemical results obtained, it was concluded that
      VOL can regenerate B cells of the pancreas in experimental diabetes and has an
      antidiabetic and protective effects on the pancreas.

PMID- 18621447
TI  - The R219K polymorphism in the ATP-binding cassette transporter 1 gene has a
      protective effect on atherothrombotic cerebral infarction in Chinese Han ethnic
      population.
AB  - The association of R219K and V825I polymorphisms of ABCA1 gene with cerebral
      infarction has been rarely reported. Here we wish to address this issue. A total
      of 476 subjects from Chinese Han ethnic population were investigated, including
      152 control individuals and 324 patients with cerebral infarction. Genotyping of
      R219K and V825I were performed by PCR-RFLP analysis. Data were analyzed using a
      statistical package. The R219K genotype frequency distributions were
      significantly different between patients with atherothrombotic cerebral
      infarction (ACI) and control individuals, with fewer KK genotypes and more RR
      genotypes in ACI patients (chi(2)=9.89, P<0.01). The K allele is less frequent
      among ACI patients than in controls (chi(2)=9.16, P<0.005). A significant
      association of KK with decreased ACI risk was exhibited, especially in male
      patients, aged patients and individuals with hypertension. These results indicate
      that the K allele of R219K polymorphism is an independent protective factor
      against ACI. In addition, though there is no association of V825I with ACI, this
      polymorphism may have certain synergistic effect with hypertension in
      susceptibility to ACI.

PMID- 18621449
TI  - Synthesis, analgesic and anti-inflammatory activities of novel 3-(4-acetamido
      benzyl)-5-substituted-1,2,4-oxadiazoles.
AB  - A series of 3-(4-acetamido-benzyl)-5-substituted-1,2,4-oxadiazoles (7a-7n) were
      synthesized and screened for analgesic and in vivo anti-inflammatory activities
      using acetic acid writhing in mice model and carrageenan-induced paw oedema
      method in mice, respectively. The analgesic activity of compounds 7i and 7m is
      superior while that of 7d, 7c, 7f and 7j is equal to the reference standard,
      diclofenac sodium. The anti-inflammatory activity of compounds 6, 7c, 7e, 7f, 7i,
      7l, 7m and 7n is found to be superior than that of diclofenac sodium which is
      used as a reference, while compounds 7d and 7g are found to be equipotent with
      the reference compound.

PMID- 18621450
TI  - Catering in a large hospital--does serving from a buffet system meet the
      patients' needs?
AB  - BACKGROUND & AIMS: It has been suggested that serving from a buffet system may
      increase food intake. This observational study estimates the energy intake in a
      representative group of patients admitted to a hospital, where the food is served
      from a buffet system. MATERIAL: One hundred and sixteen random patients were
      screened according to the NRS-2002 system and the energy requirements were
      calculated. The type of food ordered for the patients and the energy intake were
      determined. RESULT: Eighty had an NRS score of 0-2, i.e. not at nutritional risk
      and 36 a score > or = 3, i.e. at nutritional risk. Among patients with NRS score
      > or = 3 only 50% were ordered the correct menu. Only 50% of the patients had an
      energy intake < 75% of their requirements. In the group of patients, who took <
      50% of energy requirement more than 90% came from the main courses and very
      little from snacks. CONCLUSION: In-patients at nutritional risk focus should be
      on ordering the correct type of food for the main courses and especially on
      increasing the intake from snacks.

PMID- 18621452
TI  - Does counsellor's attitude influence change in a request for a caesarean in women
      with fear of birth?
AB  - BACKGROUND: the attitudes of two counsellors towards women requesting a caesarean
      section due to fear of birth were identified. One emphasised the ability to
      overcome any emotional obstacle to vaginal birth ('coping attitude'), and the
      other emphasised that the ultimate choice of mode of birth was the womans'
      ('autonomy attitude'). Two research questions were asked: (1) What are the
      predictors of change in a wish for a caesarean and of vaginal birth in women with
      fear of birth? (2) Does a change from an 'autonomy attitude' to a 'coping
      attitude' increase the number of women who change their request for a caesarean
      and who give birth vaginally? METHODS: the study population consisted of two
      samples of pregnant women with fear of birth and concurrent request for a
      caesarean, referred for crisis-oriented counselling at the antenatal clinic,
      University Hospital of North Norway between 2000-2002 (n=86) and 2004-2006
      (n=107). Data were gathered from referral letters, counseling and antenatal,
      intra- and postpartum records. FINDINGS: a coping attitude of the counsellor was
      positively associated with change in the request for a caesarean and with vaginal
      birth. A change from an autonomy attitude to a coping attitude was associated
      with a significant increase in the percentage of women who changed their desire
      for a caesarean from 77 to 93, and who had a vaginal birth from 42 to 81.
      CONCLUSION: a coping attitude was strongly associated with change in the desire
      for a caesarean and giving birth vaginally. A coping attitude can be learned
      through critical reflection and awareness of the counsellor's attitude, with
      measurable clinical results.

PMID- 18621451
TI  - Differential immunogenicity of vaccinia and HIV-1 components of a human
      recombinant vaccine in mucosal and blood compartments.
AB  - Mucosal immune responses induced by HIV-1 vaccines are likely critical for
      prevention. We report a Phase 1 safety and immunogenicity trial in eight
      participants using the vaccinia-based TBC-3B vaccine given subcutaneously to
      determine the relationship between HIV-1 specific systemic and gastrointestinal
      mucosal responses. Across all subjects, detectable levels of blood vaccinia- and
      HIV-1-specific antibodies were elicited but none were seen mucosally. While the
      vaccinia component was immunogenic for CD8(+) T lymphocyte (CTL) responses in
      both blood and mucosa, it was greater in blood. The HIV-1 component of the
      vaccine was poorly immunogenic in both blood and mucosa. Although only eight
      volunteers were studied intensively, the discordance between mucosal and blood
      responses may highlight mechanisms contributing to recent vaccine failures.

PMID- 18621453
TI  - Twelve-week biomechanical ankle platform system training on postural stability
      and ankle proprioception in subjects with unilateral functional ankle
      instability.
AB  - BACKGROUND: Functional ankle instability is defined as the subjective sensation
      of giving way or feeling joint instability after repeated episodes of ankle
      sprain. The purpose of this study was to examine the effects of 12-week
      biomechanical ankle platform system training on static postural stability and
      ankle reposition sense in subjects with unilateral functional ankle instability.
      METHODS: Twelve university students (4 females and 8 males) with unilateral
      functional ankle instability volunteered as subjects. The active and passive
      reposition senses were assessed using an isokinetic dynamometer. The mean radius
      of the center of pressure excursion was recorded during single-leg standing with
      a force platform. A 12-week training program and a progression test for
      controlling the platform in certain directions and advancing to next training
      level was given to each subject. Repeated-measures 2-way analyses of variance
      were conducted to determine differences in postural stability and ankle
      proprioception between each limb before and after the training period. FINDINGS:
      The mean radius of center of pressure on unilateral standing and the absolute
      error from pre-selected ankle angle in the functional ankle instability limb were
      significantly reduced after 12 weeks of training. INTERPRETATION: These
      improvements in postural stability appear to reflect improved neuromuscular
      ability along with enhanced functional joint stability, as ankle proprioception
      also demonstrated the same positive improvements after training.

PMID- 18621454
TI  - Relationships between organic matter, black carbon and persistent organic
      pollutants in European background soils: Implications for sources and
      environmental fate.
AB  - Black carbon (BC) and total organic carbon (TOC) contents of UK and Norwegian
      background soils were determined and their relationships with persistent organic
      pollutants (HCB, PAHs, PCBs, co-planar PCBs, PBDEs and PCDD/Fs) investigated by
      correlation and regression analyses, to assess their roles in influencing
      compound partitioning/retention in soils. The 52 soils used were high in TOC
      (range 54-460 mg/g (mean 256)), while BC only constituted 0.24-1.8% (0.88%) of
      the TOC. TOC was strongly correlated (p<0.001) with HCB, PCBs, co-PCBs and PBDEs,
      but less so with PCDD/Fs (p<0.05) and PAHs. TOC explained variability in soil
      content, as follows: HCB, 80%; PCBs, 44%; co-PCBs, 40%; PBDEs, 27%. BC also gave
      statistically significant correlations with PBDEs (p<0.001), co-PCBs (p<0.01) and
      PCBs, HCB, PCDD/F (p<0.05); TOC and BC were correlated with each other (p<0.01).
      Inferences are made about possible combustion-derived sources, atmospheric
      transport and air-surface exchange processes for these compounds.

PMID- 18621455
TI  - Functional transcranial Doppler sonography and a spatial orientation paradigm
      identify the non-dominant hemisphere.
AB  - RATIONALE: Functional transcranial Doppler sonography (fTCD) during word
      generation is well established for language lateralization. In this study, we
      evaluated a fTCD paradigm to reliably identify the non-dominant hemisphere.
      METHODS: Twenty-nine right-handed healthy subjects (27.1+/-7.6 years) performed
      the 'cube perspective test' [Stumpf, H., & Fay, E. (1983). Schlauchfiguren: Ein
      Test zur Beurteilung des raumlichen Vorstellungsvermogens. Verlag fur Psychologie
      Dr. C. J. Hogrefe, Gottingen, Toronto, Zurich] a spatial orientation task, while
      the cerebral blood flow velocity (CBFV) was simultaneously measured in both
      middle cerebral arteries (MCAs). In addition, the established word generation
      paradigm for language lateralization was performed. Subjects with atypical
      language representation were excluded. Data were analysed offline with the
      software Average, which performed a heart-cycle integration and a baseline
      correction and calculated a lateralization index (LI) with its standard error of
      the mean increase in CBFV separately for both MCAs. RESULTS: Twenty-one of 29
      subjects (72.4%) lateralized to the right hemisphere (chi2=5.828, p=0.016). The
      mean LI of the spatial orientation paradigm pointed to the right hemisphere (x =
      1.9+/-3.2) and was different from the LI of word generation (x =3.9+/
      2.2;p<0.001). There was no correlation between the LI of spatial orientation and
      word generation (R=0.095, p=0.624). Age of the subjects did not correlate with
      the LI during spatial orientation (p>0.05) but negatively with the LI during word
      generation (R=-0.468, p=0.010). The maximum increase of CBFV was greater in the
      spatial orientation (14.0%+/-3.6%) than in the word generation paradigm (9.4%+/
      4.0%; p<0.001). CONCLUSIONS: In more than two thirds of the subjects with left
      sided language dominance, the spatial orientation paradigm was able to identify
      the non-dominant hemisphere. The results suggest both paradigms to be independent
      of each other. The spatial orientation paradigm, therefore, appears to be a non
      verbal fTCD paradigm with possible clinical relevance.

PMID- 18621456
TI  - The influence of 30-day-old Streptococcus mutans biofilm on the surface of
      esthetic restorative materials--an in vitro study.
AB  - OBJECTIVE: To evaluate the effects of Streptococcus mutans biofilm/restorative
      materials interaction on surface roughness, hardness and morphology of materials
      tested. METHODS: Empress 2 (E2), Filtek Supreme (FS), Vitremer (V) and Ketac
      Molar Easymix (KM) were tested. Twenty-five disks of each material were made and
      divided into three storage groups: (1) 100% relative humidity (n=5); (2) growth
      medium (BHI and 1% sucrose) (n=5); (3) S. mutans biofilm-growth medium (n=15).
      Before storage, hardness measurements were immediately obtained from group 1
      specimens. After 30 days of storage, the specimens were cleaned in order to
      obtain the surface roughness and hardness values, besides morphology analysis by
      scanning electron microscopy. RESULTS: The surface roughness and hardness values
      obtained from E2 and FS specimens did not present statistically significant
      differences among the groups 1, 2 and 3 and between immediate and 30-day-old
      specimens of each material. However, group 3 specimens of V and KM showed
      statistically significant higher surface roughness means than other groups. Group
      1 specimens of V and KM also showed higher hardness values than the immediate
      values. Group 3 specimens of V presented decreased hardness values compared with
      other groups. The scanning electron micrographs showed an increase in surface
      degradation from group 1 to group 3 for FS, V and KM. CONCLUSIONS: Thirty-day-old
      biofilm promotes a negative effect on the surface morphology of FS, V and KM, on
      the surface roughness of V and KM and on the hardness of V.

PMID- 18621458
TI  - The effect of proximal contour on marginal ridge fracture of Class II composite
      resin restorations.
AB  - OBJECTIVES: To compare the marginal ridge fracture strength of Class II composite
      resin restorations placed with a straight or contoured matrix band using
      composite resins with different modulus of elasticity. METHODS: In 60 artificial
      first molars standardized MO-preparations were ground. Two matrix systems were
      used: (1) A straight matrix (Standard Tofflemire Matrix, KerrHawe) in Tofflemire
      retainer (Produits Dentaire). (2) A contoured matrix (Standard matrix, Palodent,
      Dentsply). In both groups, a wooden wedge and separation ring (Composi-Tight
      Gold, GDS) were placed and the matrix was burnished against the adjacent tooth.
      Three composite resins together were used (Filtek Supreme: e-modulus 13.3 GPa (3M
      ESPE), Clearfil AP-X: 16.6 GPa (Kuraray) and Clearfil Majesty Posterior: 22.0 GPa
      (Kuraray)), resulting in six groups (n=10). Teeth were mounted into a MTS servo
      hydraulic testing machine (Mini Bionix II, MTS, USA) with stylus placed on the
      marginal ridge. Samples were loaded at a crosshead speed of 1.0mm/min until
      fracture occurred. Fracture resistance data were statistically analyzed using
      ANOVA and Scheffe's post hoc test for multiple comparison of groups (p<0.05).
      RESULTS: Contoured proximal surfaces (365.5+/-87.6N) resulted in significant
      stronger marginal ridges compared to straight surfaces (290.5+/-64.2N) (p<0.001).
      Clearfil AP-X (378.1+/-94.63N) provided a higher resistance to fracture than
      Filtek Supreme (301.4+/-67.3N) (p=0.001) and Clearfil Majesty Posterior (304.5+/
      70.6N) (p=0.002). No differences were found between Filtek Supreme and Clearfil
      Majesty Posterior (p=0.890). CONCLUSION: Within the limitations of this in vitro
      study it was shown that use of a contoured matrix results in a stronger marginal
      ridge of a Class II composite resin restoration.

PMID- 18621457
TI  - Retention of fiber posts cemented at different time intervals in canals obturated
      using an epoxy resin sealer.
AB  - OBJECTIVES: To evaluate the effect of immediate versus delayed post space
      preparation and cementation on the retention of different types of fiber posts in
      canals obturated with an epoxy resin sealer. METHODS: Sixty-eight single-rooted
      human teeth were decoronated and the root canals were shaped with rotary
      instruments and obturated with gutta-percha and an epoxy resin sealer. The teeth
      were divided into four experimental groups according to the different times of
      post space preparation and cementation: immediate (group 1), 24h (group 2) and 1
      week (group 3) after root canal filling. Control group (group 4) with no root
      canal obturation was included. Two teeth were randomly selected from each group
      for SEM examination. Each group was further divided into three subgroups of five
      teeth each (n=5), according to the type of post and the materials used for luting
      the posts. A push-out test was performed and differences among experimental
      groups were analyzed with two-way ANOVA and Tukey test (alpha=0.05). RESULTS:
      Interfacial strength values achieved in group 1, where an immediate cementation
      was performed, were significantly lower (p<0.05) than those in group 2 and group
      3 in which post cementation was performed 24h or 1 week after the root canal
      filling. Post type affected post retention, FRC Postec and DT Light Post posts
      achieved higher interfacial strengths than ENA Post (p<0.05). SEM examination
      revealed a more conspicuous presence of sealer remnants on the walls of
      immediately prepared post spaces. CONCLUSIONS: Delayed cementation of fiber post
      resulted in higher retentive strengths irrespective of the post type.

PMID- 18621459
TI  - Differences in color, translucency and fluorescence between flowable and
      universal resin composites.
AB  - OBJECTIVES: To evaluate the optical properties such as color, translucency and
      fluorescence of flowable resin composites, and compare them with the
      corresponding shade universal resin composites of the same brand. METHODS: Four
      brands of flowable and universal resin composites of the same shade designation
      (A2) were investigated. Color of specimens (2mm in thickness) was measured after
      polymerization on a reflection spectrophotometer over background of white, black
      and each corresponding composite material itself. Color differences
      (DeltaE(ab)(*)) between each combination of resin composites were determined.
      Translucency parameter (TP) and color difference by the fluorescent emission
      (DeltaE(ab)(*)-FL) of materials were also calculated. Differences in the optical
      properties of flowable and universal resin composites were analyzed with one-way
      ANOVA. RESULTS: DeltaE(ab)(*) between the flowable and the corresponding
      universal resin composites was in the range of 1.0-6.0 DeltaE(ab)(*) units, which
      was perceptible (DeltaE(ab)(*)>2.6) in three brands. Flowable resin composites
      revealed lower TP values in two of the four brands. DeltaE(ab)(*) between
      flowable and the corresponding universal resin composites was influenced by their
      difference in translucency. All the four universal resin composites and two
      flowable resin composites showed fluorescent peak, and the range of DeltaE(ab)(*)
      FL was 0.3-2.3 DeltaE(ab)(*) units. CONCLUSIONS: Optical properties of flowable
      and universal resin composites was significantly different (p<0.05); therefore,
      differences in color, translucency and fluorescence between the flowable and the
      corresponding universal resin composites should be considered for clinically
      acceptable color matching.

PMID- 18621460
TI  - Bonding effectiveness and interfacial characterization of a HEMA/TEGDMA-free
      three-step etch&rinse adhesive.
AB  - OBJECTIVES: Small and hydrophilic monomers as HEMA and TEGDMA can easily
      penetrate human tissues. For biocompatibility issues it is therefore better to
      avoid such monomers in dental adhesive formulations. The purpose of this study
      was (1) to determine the micro-tensile bond strength (muTBS) to enamel/dentin of
      a HEMA/TEGDMA-free three-step etch&rinse adhesive (cmf Adhesive System, Saremco),
      and (2) to characterize it's interfacial interaction with enamel/dentin using
      transmission electron microscopy (TEM). METHODS: Twelve intact freshly extracted
      human third molars were used for muTBS. The three-step etch&rinse adhesive
      OptiBond FL (Kerr) served as control adhesive. After bonding procedures and
      subsequent composite build-up (Z100, 3M ESPE), specimens were sectioned to sticks
      and trimmed at the interface to a cylindrical hour-glass shape. TEM section of
      non-demineralized and demineralized sections were prepared by ultra-microtomy and
      examined. RESULTS: The muTBS of the cmf Adhesive System to enamel was not
      statistically significantly different from that of the control (OptiBond FL)
      adhesive (p=0.3512); the muTBS to dentin was however significantly lower
      (p<0.0001). TEM showed a tight interface at enamel for both adhesives. A
      relatively thick, completely demineralized and acid-resistant hybrid layer was
      formed at dentin. Some degree of spot- and cluster-like nano-leakage was observed
      with cmf Adhesive System, but did not differ in extent and form in comparison to
      that observed with the OptiBond FL control. CONCLUSIONS: The new three-step
      adhesive cmf Adhesive System showed indications of good bonding effectiveness,
      certainly to enamel and only significantly lower to dentin, when compared to the
      gold-standard adhesive. The latter may be related to the adapted HEMA/TEGDMA-free
      formulation and the somewhat lower mechanical properties.

PMID- 18621461
TI  - Neurological outcome and inflammation after cardiac arrest--effects of protein C
      in rats.
AB  - BACKGROUND: The response of the human body to cardiac arrest (CA) and
      cardiopulmonary resuscitation is characterised by excessive coagulation,
      inadequate endogenous anti-coagulation and fibrinolysis as well as an
      inflammatory syndrome that closely resembles the immunological profile observed
      in patients with sepsis. Recombinant human activated protein C (rhAPC) has been
      found to be protective in severe sepsis and in animal models of stroke and spinal
      cord injury. In the present study, we evaluated the effects of rhAPC on
      neurological outcome after CA in rats. METHODS: After 6 min of CA and subsequent
      cardiopulmonary resuscitation, male Wistar rats were randomized into 3 treatment
      groups: high dose rhAPC (2 mg/kg bolus and 0.1 mg/(kg h) for 6 h), low dose rhAPC
      (0.5 mg/kg and 0.025 mg/(kg h) for 6 h), and placebo (n=12 per treatment and
      reperfusion time). Neurological outcome was determined using a tape removal test
      and a composite neurological deficit score (NDS). As secondary measurements, we
      evaluated overall and neuronal survival, hippocampal caspase activity and
      inflammatory markers. RESULTS: No difference between groups was found with the
      NDS. The tape removal test showed only a transitory improvement in the low dose
      group at 3 d after CA (P=0.041). No significant differences were observed for
      secondary measurements. CONCLUSION: A clear and lasting effect of rhAPC on
      neurological outcome or inflammation after CA could not be shown in this study
      but the detailed analysis of the postresuscitation syndrome given here builds a
      firm basis for further research.

PMID- 18621462
TI  - A high peak current 150-J fixed-energy defibrillation protocol treats recurrent
      ventricular fibrillation (VF) as effectively as initial VF.
AB  - OBJECTIVE: We tested the hypothesis that the frequency of shock success differs
      between initial and recurrent episodes of ventricular fibrillation (VF). METHODS:
      Out-of-hospital cardiac arrest patients presenting with VF from December 1996 to
      February 2007 defibrillated using an AED with a fixed-energy protocol (150 J)
      (Philips Medical Systems, Seattle, WA) were included for analysis. We defined
      shock success as termination of VF within 5s post-shock (either asystole or
      organized rhythm). Generalized estimating equation (GEE) analysis was used to
      adjust for the interrelatedness of shocks within each patient. RESULTS: One
      hundred and three events occurred during the study period. Patient
      characteristics included: mean age 64.4 years, 82.5% male, and 81.6% bystander
      witnessed. Synchronized call-to-shock time was 6.4+/-2.3 min (mean+/-S.D.). VF
      recurred in 64 (62.1%) patients. Two hundred and fifty-seven shocks delivered for
      initial (101) or recurrent (156) VF were available for analysis. Initial shocks
      terminated VF in 93/101 (92.1%); subsequent shocks terminated recurrent VF in
      140/156 (89.7%). GEE odds ratio for shock type (initial versus refibrillation)
      was 1.10 (95% CI 0.37-3.24, p=0.87). After adjusting for potential confounders,
      shock type remained insignificant (OR 1.14, 95% CI 0.41-3.2, p=0.80). We observed
      no significant difference in ROSC (34.4% versus 46.2%, p=0.23) or survival (37.5%
      versus 41.0%, p=0.72) between those with and without VF recurrence. CONCLUSIONS:
      We observed no significant difference in the frequency of shock success between
      initial and recurrent episodes of VF using this AED with a 150 J fixed-energy
      protocol. VF recurrence is common and does not adversely affect shock success,
      ROSC or survival.

PMID- 18621464
TI  - Prognostic significance of the detection of human papilloma virus L1 protein in
      smears of mild to moderate cervical intraepithelial lesions.
AB  - OBJECTIVE: To investigate whether it is possible to use detection of the human
      papillomavirus (HPV) L1 capsid protein to predict the course of mild or moderate
      cervical intraepithelial neoplasia (CIN). STUDY DESIGN: Pap smears from 279 women
      in whom CIN 1 and CIN 2 had been diagnosed by cytology and histology, who were
      known to have a high-risk HPV status and had a median follow-up of 25 months,
      were immunohistochemically stained for the HPV L1 protein. The staining results
      were correlated with the clinical course of the disease. RESULTS: HPV L1-positive
      patients showed regression in 49.1% of cases, stable disease in 41.5%, and
      progressive disease in 9.4%, whereas HPV L1-negative women had progression in
      25.9% of cases (regression 33.3%, stable disease 40.7%; p=0.001). The effect was
      clearest in the group under 30 years of age. HPV L1-negative patients experienced
      progression significantly more often than women with a positive HPV L1 test (odds
      ratio 3.391). CONCLUSIONS: HPV L1-positivity was found to have prognostic
      significance in relation to disease progression in women with CIN 1 and CIN 2 and
      particularly in those less than 30 years of age.

PMID- 18621463
TI  - Volume resuscitation from hemorrhagic shock with albumin and hexaPEGylated human
      serum albumin.
AB  - The effect of restoring intravascular volume with polyethylene glycol (PEG)
      conjugated to human serum albumin (PEG-Alb) on systemic parameters and
      microvascular hemodynamics after hemorrhagic shock resuscitation was studied in
      the hamster window chamber model. Moderate hemorrhagic shock was induced by
      controlled arterial bleeding of 50% of blood volume, and hypovolemia was
      maintained for 1h. Fluid resuscitation was accomplished by infusion of 25% of
      blood volume and recovery was followed over 90 min. The PEG-Alb (six chains of
      maleimide phenyl PEG conjugated human serum albumin at 4%) resuscitation group
      was compared human serum albumin (HSA) at 5% (HSA5) and 10% (HSA10) protein
      concentrations. Systemic parameters, microvascular perfusion and capillary
      perfusion (functional capillary density, FCD) were measured by noninvasive
      methods. Hyperoncotic solutions provided rapid restoration of blood pressure,
      blood gas parameters and microvascular perfusion. Systemic and microvascular
      recovery was best and most rapid with PEG-Alb and followed by HSA10 and HSA5.
      Only recovery with PEG-Alb was sustained beyond 90 min. Hemodynamic functional
      benefits of PEG-Alb and the potential disadvantages associated with HSA, suggest
      PEG-Alb as better resuscitation solution.

PMID- 18621465
TI  - What is new?

PMID- 18621466
TI  - Transport of fecal bacteria by boots and vehicle tires in a rural Alaskan
      community.
AB  - People living without piped water and sewer can be at increased risk for diseases
      transmitted via the fecal-oral route. One rural Alaskan community that relies on
      hauling water into homes and sewage from homes was studied to determine the
      pathways of fecal contamination of drinking water and the human environment so
      that barriers can be established to protect health. Samples were tested for the
      fecal indicator, Escherichia coli, and the less specific indicator group, total
      coliforms. Shoes transported fecal contamination from outside to floor material
      inside buildings. Contamination in puddles on the road, in conjunction with
      contamination found on all-terrain vehicle (ATV) tires, supports vehicle traffic
      as a mechanism for transporting contamination from the dumpsite or other source
      areas to the rest of the community. The abundance of fecal bacteria transported
      around the community on shoes and ATV tires suggests that centralized measures
      for waste disposal as well as shoe removal in buildings could improve sanitation
      and health in the community.

PMID- 18621467
TI  - Web-based GIS for collaborative planning and public participation: an application
      to the strategic planning of wind farm sites.
AB  - Spatial planning typically involves multiple stakeholders. To any specific
      planning problem, stakeholders often bring different levels of knowledge about
      the components of the problem and make assumptions, reflecting their individual
      experiences, that yield conflicting views about desirable planning outcomes.
      Consequently, stakeholders need to learn about the likely outcomes that result
      from their stated preferences; this learning can be supported through enhanced
      access to information, increased public participation in spatial decision-making
      and support for distributed collaboration amongst planners, stakeholders and the
      public. This paper presents a conceptual system framework for web-based GIS that
      supports public participation in collaborative planning. The framework combines
      an information area, a Multi-Criteria Spatial Decision Support System (MC-SDSS)
      and an argumentation map to support distributed and asynchronous collaboration in
      spatial planning. After analysing the novel aspects of this framework, the paper
      describes its implementation, as a proof of concept, in a system for Web-based
      Participatory Wind Energy Planning (WePWEP). Details are provided on the specific
      implementation of each of WePWEP's four tiers, including technical and structural
      aspects. Throughout the paper, particular emphasis is placed on the need to
      support user learning throughout the planning process.

PMID- 18621468
TI  - Hybrid spectral domain method for attenuation slope estimation.
AB  - Attenuation estimation methods for medical ultrasound are important because
      attenuation properties of soft tissue can be used to distinguish between benign
      and malignant tumors and to detect diffuse disease. The classical spectral shift
      method and the spectral difference method are the most commonly used methods for
      the estimation of the attenuation; however, they both have specific limitations.
      Classical spectral shift approaches for estimating ultrasonic attenuation are
      more sensitive to local spectral noise artifacts and have difficulty in
      compensating for diffraction effects because of beam focusing. Spectral
      difference approaches, on the other hand, fail to accurately estimate attenuation
      coefficient values at tissue boundaries that also possess variations in the
      backscatter. In this paper, we propose a hybrid attenuation estimation method
      that combines the advantages of the spectral difference and spectral shift
      methods to overcome their specific limitations. The proposed hybrid method
      initially uses the spectral difference approach to reduce the impact of system
      dependent parameters including diffraction effects. The normalized power spectrum
      that includes variations because of backscatter changes is then filtered using a
      Gaussian filter centered at the transmit center frequency of the system. A
      spectral shift method, namely the spectral cross-correlation algorithm is then
      used to compute spectral shifts from these filtered power spectra to estimate the
      attenuation coefficient. Ultrasound simulation results demonstrate that the
      estimation accuracy of the hybrid method is better than the centroid downshift
      method (spectral shift method), in uniformly attenuating regions. In addition,
      this method is also stable at boundaries with variations in the backscatter when
      compared with the reference phantom method (spectral difference method).
      Experimental results using tissue-mimicking phantom also illustrate that the
      hybrid method is more robust and provides accurate attenuation estimates in both
      uniformly attenuating regions and across boundaries with backscatter variations.
      The proposed hybrid method preserves the advantages of both the spectral shift
      and spectral difference approaches while eliminating the disadvantages associated
      with each of these methods, thereby improving the accuracy and robustness of the
      attenuation estimation.

PMID- 18621469
TI  - Utility of a tumor-mimic model for the evaluation of the accuracy of HIFU
      treatments. results of in vitro experiments in the liver.
AB  - Presented in this article is a tumor-mimic model that allows the evaluation,
      before clinical trials, of the targeting accuracy of a high intensity focused
      ultrasound (HIFU) device for the treatment of the liver. The tumor-mimic models
      are made by injecting a warm solution that polymerizes in hepatic tissue and
      forms a 1 cm discrete lesion that is detectable by ultrasound imaging and gross
      pathology. First, the acoustical characteristics of the tumor-mimics model were
      measured in order to determine if this model could be used as a target for the
      evaluation of the accuracy of HIFU treatments without modifying HIFU lesions in
      terms of size, shape and homogeneity. On average (n = 10), the attenuation was
      0.39 +/- 0.05 dB.cm(-1) at 1 MHz, the ultrasound propagation velocity was 1523 +/
      1 m.s(-1) and the acoustic impedance was 1.84 +/- 0.00 MRayls. Next, the tumor
      mimic models were used in vitro in order to verify, at a preclinical stage, that
      lesions created by HIFU devices guided by ultrasound imaging are properly
      positioned in tissues. The HIFU device used in this study is a 256-element phased
      array toroid transducer working at a frequency of 3 MHz with an integrated
      ultrasound imaging probe working at a frequency of 7.5 MHz. An initial series of
      in vitro experiments has shown that there is no significant difference in the
      dimensions of the HIFU lesions created in the liver with or without tumor-mimic
      models (p = 0.3049 and p = 0.8796 for the diameter and depth, respectively). A
      second in vitro study showed that HIFU treatments performed on five tumor-mimics
      with safety margins of at least 1 mm were properly positioned. The margins
      obtained were on average 9.3 +/- 2.7 mm (min. 3.0 - max. 20.0 mm). This article
      presents in vitro evidence that these tumor-mimics are identifiable by ultrasound
      imaging, they do not modify the geometry of HIFU lesions and, thus, they
      constitute a viable model of tumor-mimics indicated for HIFU therapy.

PMID- 18621470
TI  - The periprostatic autonomic nerves--bundle or layer?
AB  - BACKGROUND: The functional outcome of a nerve-sparing radical prostatectomy (RP)
      depends on the knowledge of autonomic nerve distribution in correlation to the
      prostate. OBJECTIVE: Recent literature has focused predominantly on the anterior
      prostate; this study evaluates the nerve distribution on the entire prostate,
      using a two-dimensional approach. DESIGN, SETTING, AND PARTICIPANTS: From 17 non
      nerve-sparing (NS) RP specimens, 77 whole mounted serial sections were
      immunostained with PGP9.5 and analyzed. INTERVENTION: Each prostate half was
      divided into 12 sectors (three levels: apex, mid-part, base; four courses:
      anterior, anterolateral, posterolateral, posterior). MEASUREMENTS: The
      extracapsular nerves were counted and classified by size (>200microm or
      <or=200microm). RESULTS AND LIMITATIONS: Approximately two-thirds of the nerves
      were located in the posterolateral while 26.3/27.0% were located in the anterior
      and anterolateral. In the anterolateral, along the base-apex direction, the
      nerves decreased whereas they increased in the posterior. In the anterior, the
      highest counts were found in the mid-prostate. PGP 9.5 stain helps to determine
      the extracapsular nerve distribution, however, it does not allow a functional
      allocation. CONCLUSIONS: The nerve course expands from the base in the mid-part
      to the anterior sector, before it narrows towards the apex in the posterior
      lateral and posterior sectors. Therefore, it is recommended that the surgeon
      focus on nerve preservation in particular at the apex, starting in the anterior
      at the mid section as well as the common posterolateral course.

PMID- 18621471
TI  - Editorial comment on: the periprostatic autonomic nerves--bundle or layer?

PMID- 18621472
TI  - Editorial comment on: the periprostatic autonomic nerves--bundle or layer?

PMID- 18621473
TI  - A computer support system for neurological anatomical diagnosis.
AB  - OBJECTIVES: Accurate neurological diagnoses are often difficult to make due to
      the complexity of the neuroanatomy involved. This study was performed to evaluate
      the usefulness of a computer system with easily retrievable anatomical
      information as a support for arriving at more accurate anatomic diagnoses.
      PATIENTS AND METHODS: Anatomical information from an initial physical examination
      was programmed into a computer with stored neuroanatomical charts of the brain,
      spinal cord and peripheral nerves. The information generated a graphic display of
      possible lesions with suggestions for further examination. These suggestions were
      then followed and further data entered. This data entry generated a new graphic
      display with reduced lesion possibilities. Iterations were then followed to
      narrow the possibilities for diagnosis further, until a final anatomical
      diagnosis was reached. This method was applied to three hypothetical examples and
      a number of clinical cases. Here we report three clinical cases in which this
      method was particularly useful in making a diagnosis. RESULTS: Using computer
      iterations, the system was able to pinpoint one or more presumptive causative
      lesions in the CNS or PNS based on known neuronal pathways or nuclei. CONCLUSION:
      The results indicate that suitably used, computer memory, by virtue of its large
      capacity, accuracy and fast recall, can supplement human memory in reaching
      accurate anatomical diagnoses of neurological lesions.

PMID- 18621474
TI  - The new challenge of stem cell: brain tumour therapy.
AB  - The surprising similarity of much brain tumour behavior to the intrinsic
      properties of the neural stem/progenitor cell has triggered a recent interest in
      both arming stem cells to track and help eradicate tumours and in viewing stem
      cell biology as somehow integral to the emergence and/or production of the
      neoplasm itself. Moreover, based on the unique capacity of neural stem cells
      (NSCs) to migrate throughout the brain and to target invading tumour cells, the
      transplantation of NSCs offers a new potential therapeutic approach as a cell
      based delivery system for gene therapy in brain tumours. On the one hand, both
      stem cells and cancer cells are thought to be capable of unlimited proliferation.
      While on the other, many tumours and cancer cell lines express stem cell markers,
      suggesting either that cancer cells resemble stem cells or that cancers contain
      stem-like cells. In this review we highlight the close relationship between
      normal neural stem cells and brain tumour stem cells and also suggest the
      possible clinical implications that these similarities could offer.

PMID- 18621475
TI  - Adoptive transfer of pTRP2-specific CTLs expanding by bead-based artificial
      antigen-presenting cells mediates anti-melanoma response.
AB  - Cytotoxic CD8(+) T cells are key effectors in the immunotherapy of malignant and
      viral diseases. However, the lack of efficient methods for their in vitro priming
      and expansion has become a bottleneck to the development of vaccines and adoptive
      transfer strategies. Synthetic artificial antigen-presenting cells (aAPCs) are
      now emerging as an attractive tool for eliciting and expanding CTL responses.
      This study reported a novel approach for targeting malignant melanoma with pTRP2
      specific cytotoxic T lymphocytes (CTLs) expanded from the C57BL/6 splenocytes by
      multiple stimulations with aAPCs made by coating H-2K(b)-Ig/pTRP2 dimeric
      complexes, anti-CD28 antibody, 4-1BBL molecules and CD83 molecules to cell-sized
      latex beads. The induced CTLs exhibited specific lysis against RMA-S cells pulsed
      with the peptide pTRP2 and H-2K(b+) melanoma cells expressing TRP2, while a
      murine Lewis lung carcinoma cell line 3LL could not be recognized by the CTLs.
      The peptide-specific activity was inhibited by anti-H-2K(b) monoclonal antibody
      Y3. Adoptive Transfer of CTLs specific for malignant melanoma expanding by the
      aAPCs can mediate effective anti-melanoma response. These results suggested the
      bead-based aAPCs coated with an MHC-Ig/peptide complex, anti-CD28 antibody, 4
      1BBL and CD83 could provide a useful tool for the reproducible expansion of
      specific CTLs for adoptive immunotherapy.

PMID- 18621476
TI  - Treatment of bromoamine acid wastewater using combined process of micro
      electrolysis and biological aerobic filter.
AB  - The wastewater originated from the production of bromoamine acid was treated in a
      sequential system of micro-electrolysis (ME) and biological aerobic filter (BAF).
      Decolorization and COD(Cr) removal rate of the proposed system was investigated
      with full consideration of the influence of two major controlling factors such as
      organic loading rate (OLR) and hydraulic retention time (HRT). The removal rate
      of COD(Cr) was 81.2% and that of chrominance could be up to 96.6% at an OLR of
      0.56 kg m(-3)d(-1) when the total HRT was 43.4h. Most of the chrominance was
      removed by the ME treatment, however, the BAF process was more effective for
      COD(Cr) removal. The GC-MS and HPLC-MS analysis of the contaminants revealed that
      1-aminoanthraquinone, bromoamine acid and mono-sulfonated 1,2-dichlorobenzene
      were the main organic components in the wastewater. The reductive transformation
      of the anthraquinone derivatives in the ME reactor improved the biodegradability
      of the wastewater, and rendered the decolorization. After long-term of operation,
      it was observed that the predominant microorganisms immobilized on the BAF
      carriers were rod-shaped and globular. Four bacterial strains with apparent 16S
      rDNA fragments in the Denaturing Gradient Gel Electrophoresis (DGGE) profiles of
      BAF samples were identified as Variovorax sp., Sphingomonas sp., Mycobacterium
      sp., and Microbacterium sp.

PMID- 18621477
TI  - Thulium hydroxide: a new coprecipitant for speciation of chromium in natural
      water samples.
AB  - A coprecipitation procedure has been established for chromium speciation in
      natural water samples. The procedure is based on the coprecipitation of Cr(III)
      on thulium hydroxide precipitate. After reduction of Cr(VI) to Cr(III) by using
      potassium iodide, the presented method was applied to the determination of the
      total chromium. The level of Cr(VI) is calculated by difference of total chromium
      and Cr(III) levels. The procedure was optimized for some analytical parameters
      including pH, sample volume, matrix effects, etc. The detection limits based on
      3sigma criterion were 0.87 microg L(-1) for Cr(III) and 1.18 microg L(-1) for
      Cr(VI). The procedure presented was validated by the analysis of BCR-144R Sewage
      Sludge (domestic origin). The presented method was applied for the speciation of
      chromium in environmental sample with satisfactory results (recoveries>95%,
      R.S.D.s<10%).

PMID- 18621478
TI  - Identification of sustainable flux in the process of using flat-sheet membrane
      for simultaneous thickening and digestion of waste activated sludge.
AB  - The influences of mixed liquor properties on critical flux were investigated in
      the membrane for simultaneous thickening and digestion of activated sludge (MSTD)
      process, and the sustainable operation of the MSTD process was examined by
      employing sub-critical operation. The critical flux significantly decreased with
      the increase of operation time due to the variations of sludge properties in the
      MSTD process. Test results showed that mixed liquor suspended solids (MLSS),
      capillary suction time (CST), soluble microbial products (SMP) and chemical
      oxygen demand concentrations of colloids (COD(c)) were found to have significant
      influences on critical flux while the extracellular polymeric substances (EPS)
      had mild impacts. MLSS was then chosen as an indicated parameter, and an
      empirical relationship was established to predict the variation of critical flux
      in the MSTD process. The variable sub-critical flux operation was proposed to
      realize the sustainable operation according to the changing law of the critical
      flux during the MSTD process. The result showed that the membrane fouling
      potential in the MSTD process could be controlled at an operationally accepted
      condition by the variable sub-critical flux operation.

PMID- 18621479
TI  - Trace elements partitioning during co-firing biomass with lignite in a pilot
      scale fluidized bed combustor.
AB  - This study describes the partitioning of 18 trace elements (As, Ba, Cd, Co, Cr,
      Cu, Li, Mn, Mo, Ni, P, Pb, Sb, Se, Sn, Tl, V, Zn) and 9 major and minor elements
      (Al, Ca, Fe, K, Mg, Na, S, Si, Ti) during co-firing of olive residue, hazelnut
      shell and cotton residue with high sulfur and ash content lignite in 0.3 MW(t)
      Middle East Technical University (METU) Atmospheric Bubbling Fluidized Bed
      Combustor (ABFBC) test rig with limestone addition. Concentrations of trace
      elements in coal, biomass, limestone, bottom ash, cyclone ash and filter ash were
      determined by inductively coupled plasma optical emission and mass spectroscopy
      (ICP-OES and ICP-MS). Partitioning of major and minor elements are influenced by
      the ash split between the bottom ash and fly ash and that the major proportion of
      most of the trace elements (As, Ba, Co, Cr, Cu, Li, Mn, Mo, Ni, Pb, Tl, V and Zn)
      are recovered in fly ash when firing lignite only. Co-firing lignite with biomass
      enhances partitioning of these elements to fly ash. Co-firing also shifts the
      partitioning of Cd, P, Sb and Sn from bottom to fly ash.

PMID- 18621480
TI  - Effects of transition metal and sulfide on the reductive dechlorination of carbon
      tetrachloride and 1,1,1-trichloroethane by FeS.
AB  - Reductive dechlorination of carbon tetrachloride (CT) and 1,1,1-trichloroethane
      (1,1,1-TCA) by FeS with transition metals (Cu(II), Co(II), and Ni(II)) and
      hydrosulfide was characterized in this study. The batch kinetic experiments were
      conducted by spiking each stock solution of CT and 1,1,1-TCA into 33 g/L of FeS
      suspensions with and without transition metals at pH 7.5. No significant
      enhancement was observed in the reductive dechlorination of target compounds by
      FeS with 1mM transition metals. However, except the addition of Cu(II), the
      reduction rate of 1,1,1-TCA increased with increasing the concentration of
      transition metals. The rate constants with 10mM Co(II) and Ni(II) were 0.06 and
      0.11h(-1), approximately 1.3 and 3.0 times greater than those by FeS alone. The
      addition of 20mM HS(-) also increased the rate constants of 1,1,1-TCA by FeS by
      one order of magnitude. SEM analysis showed that the addition of transition metal
      (Ni(II)) and HS(-) caused a noticeable morphologic change of FeS surface. The
      transition metal added was substituted by the structural iron resulting in the
      decrease of iron content of FeS (52.6-46.9%). One third of the transition metal
      in FeS suspension existed as zero-valent form playing a catalyst role to
      accelerate the reaction kinetics.

PMID- 18621481
TI  - Effects of activated sludge on the degradation of chlorate in soils under varying
      environmental conditions.
AB  - Incubation experiments were conducted to examine the effects of activated sludge
      on degradation of chlorate in soils. The results show that application of
      activated sludge could significantly promote the decomposition of soil chlorate
      though the degradation rate of chlorate did not necessarily increase with
      increasing application rate of the sludge. The effectiveness of activated sludge
      on soil chlorate degradation was significantly affected by temperature, moisture
      content and pH. There is a tendency that the rate of chlorate decomposition
      increased with increasing temperature and moisture content until optimal values
      of temperature and moisture content were reached. This can be attributed to the
      enhanced activity of chlorate-reducing microorganisms in hot and more reducing
      soil conditions. Soil pH also had important controls on the decomposition of
      chlorate. The experimental results demonstrate that neutral pH more favoured the
      degradation of soil chlorate, compared to either acidic or alkaline pH. While
      soil organic matter content could affect chlorate decomposition, its impact on
      the effectiveness of activated sludge on chlorate degradation was minor. This
      study has implications for developing cost-effective techniques for remediating
      chlorate-contaminated soils, particularly in the longan-producing countries.

PMID- 18621482
TI  - Enhanced degradation of p-chlorophenol in a novel pulsed high voltage discharge
      reactor.
AB  - The yields of active specie such as ozone, hydrogen peroxide and hydroxyl radical
      were all enhanced in a novel discharge reactor. In the reactor, the original
      formation rate of hydroxyl radical was 2.27 x 10(-7) mol L(-1)s(-1), which was
      about three times than that in the contrast reactor. Ozone was formed in gas
      phase and was transferred into the liquid. The characteristic of mass transfer
      was better in the novel reactor than that in the contrast reactor, which caused
      much higher ozone concentration in liquid. The dissociation of hydrogen peroxide
      was more evident in the former, which promoted the formations of hydroxyl
      radical. The p-chlorophenol (4-CP) degradation was also enhanced. Most of the
      ozone transferred into the liquid and hydrogen peroxide generated by discharge
      could be utilized by the degradation process of 4-CP. About 97% 4-CP was removed
      in 36 min discharge in the novel reactor. Organic acids such as formic, acetic,
      oxalic, propanoic and maleic acid were generated and free chloride ions were
      released in the degradation process. With the formation of organic acid, the pH
      was decreased and the conductivity was increased.

PMID- 18621483
TI  - Impact of apoE deficiency during synaptic remodeling in the mouse olfactory bulb.
AB  - In this study we examined the role of apoE on the rate of synaptic recovery in
      the olfactory bulb (OB) following olfactory epithelium (OE) lesioning in mice. We
      used both immunoblotting and immunohistochemical techniques to compare the
      density of OB synaptophysin (Syn, a synaptic marker) in apoE-gene
      deficient/knockout (KO) mice and wild-type (WT) mice following OE lesion. We
      found that the whole bulb concentrations of Syn, measured by immunoblotting,
      declined sharply following injury in both WT and KO mice during the degenerative
      phase (3-7 days). After this initial decline, the Syn concentration gradually
      increased to normal levels by 56 days in WT mice. In contrast, Syn concentration
      in KO mice did not recover by day 56 when Syn density in WT was essentially
      normal. Glomerular Syn density, measured by immunohistochemistry, found a lower
      density in KO mice at all time points post-lesion. This lower concentration of
      whole bulb Syn parallels the slower recovery of glomerular area in KO mice. The
      data indicate that apoE deficiency in KO mice is associated with a delayed
      recovery of the glomerular area and a slower recovery in Syn concentration in the
      OB.

PMID- 18621484
TI  - Is mirror therapy all it is cracked up to be? Current evidence and future
      directions.

PMID- 18621485
TI  - Invivo insulin deficiency as a potential etiology for demyelinating disease.
AB  - Demyelinating disease is pathologically characterized by the death of mature
      oligodendrocytes that normally synthesize myelin to perform insulating functions.
      Moreover, demyelinating disease also results in the failure of remyelination
      process in which oligodendrocyte progenitor cells reactivate and differentiate
      into new oligodendrocytes. Thus, this disease reflects decreased nerve conduction
      velocity and eventually dysfunction of the nervous system. A notable fact in the
      clinic is that demyelination is one of the most common diabetes-induced
      complications, implying that demyelinating disease may be relevant to insulin
      deficiency in vivo. However, the explicit pathological relationship between
      demyelination and diabetes remains unclear. Mainstream theories posit that
      demyelinating disease is an autoimmune disease arising from abnormal
      immunological reactions, but this perspective is limited when applied to the
      clinic. Olig1 is a vital transcription factor involved in oligodendrogenesis and
      is essential for the survival and maturation of oligodendrocyte progenitor cells.
      Furthermore, Olig1 is required for the onset of remyelination in adults. In the
      present study, we serendipitously found by means of protein immunoblot that the
      expression of nuclear Olig1 was inhibited when mouse oligodendrocyte progenitor
      cells were cultured in the absence of insulin. Combining this finding with the
      clinical relevance of demyelination and diabetes, we hypothesize that in vivo
      insulin deficiency impairs the reactivation and differentiation of
      oligodendrocyte progenitor cells through downregulation of nuclear Olig1
      expression and therefore hinders the remyelination, which is an important process
      required for functional recovery in demyelinating disease. This hypothesis
      implies that in vivo insulin deficiency may be a novel etiological cause of
      demyelinating disease and thus contribute to improved the clinical therapies for
      remyelination repair. We suggest that sustaining normal insulin levels and stable
      nuclear Olig1 expression in vivo can be new therapeutic targets for remyelination
      repair and diabetic neuropathy. In addition, with respect to the clinical
      transplantation of oligodendrocyte progenitor cells for remyelination repair,
      supplementing cell suspensions that are to be transplanted with appropriate doses
      of insulin potentially may facilitate adaptation of the transplanted progenitor
      cells to the heterogeneous and pathological environment in vivo and eventually
      improve the efficacy of the cellular transplantation.

PMID- 18621486
TI  - S100 protein expression distinguishes metanephric adenomas from other renal
      neoplasms.
AB  - Metanephric adenoma is a benign renal neoplasm with morphologic features similar
      to those of malignant renal neoplasms, such as papillary renal cell carcinoma
      (RCC) and Wilms' tumor. Different methods have been used to distinguish between
      metanephric adenoma and papillary RCC and Wilms' tumor. However, some techniques
      are not always available, such as certain immunohistochemical stains,
      cytogenetics, molecular genetics, and electron microscopy. In the current study,
      we compared the expression of S100 protein in 15 cases of metanephric adenoma, 10
      cases of Wilms' tumor, and 13 cases of papillary RCC. Our results revealed strong
      expression of S100 proteins in all cases of metanephric adenoma, weak expression
      in two cases of Wilms' tumor, and no expression in any of the cases of papillary
      RCC. These findings indicate that S100 could be a useful and accessible tool for
      the diagnosis of metanephric adenoma.

PMID- 18621487
TI  - Reduced cardio-respiratory coupling in acute alcohol withdrawal.
AB  - BACKGROUND: Chronic alcoholism represents a risk factor for cardiac arrhythmias.
      One underlying mechanism is a sympathetically dominated autonomic imbalance. This
      is especially apparent during acute withdrawal from alcohol. Since linear
      analysis of heart rate variability may not be entirely adequate to detect such
      autonomic dysfunction in acute alcohol withdrawal, we applied novel non-linear
      parameters and measures for cardio-respiratory coupling. METHODS: 20 patients
      suffering from acute alcohol withdrawal syndrome and 20 controls were included.
      For patients, heart rate and respiration were recorded on admission, after
      medication and at discharge. From these data, complexity measures (symbolic
      dynamics, approximate entropy) of heart rate modulation and respiration as well
      as parameters for cardio-respiratory coupling (coherence, cross-approximate
      entropy) which relate to vagal function were calculated. RESULTS: Heart rate
      modulation was significantly less complex in patients acutely admitted for
      alcohol withdrawal. Furthermore, coupling between beat-to-beat (RR) intervals and
      respiration time series was significantly diminished. Of the parameters assessed,
      cross-approximate entropy showed a trend for correlation with symptom severity.
      CONCLUSION: These data indicate diminished vagal function in acute alcohol
      withdrawal. Applying the methods described thus allows a sensitive detection of
      vagal neuropathy in this disease.

PMID- 18621488
TI  - Pilot trials in Australia on eradication of footrot by flock specific
      vaccination.
AB  - Footrot is a contagious disease of ruminants requiring strains of Dichelobacter
      nodosus that possess virulence factors including proteases and fimbriae. Sheep
      can be immunised against footrot using vaccine-containing fimbriae, either native
      or recombinant. The fimbriae are responsible for the serological K-agglutination
      reaction, which has been used to classify field isolates into nine major
      serogroups. The range of protection conferred by vaccination is largely
      restricted to the serogroup involved, but antigenic competition precludes
      effective vaccination with multivalent vaccines that contain all serogroups.
      However, vaccination with specific bivalent recombinant fimbrial vaccine led to
      eradication of virulent footrot from small ruminants in Nepal and the same result
      was obtained in Bhutan using a specific whole cell vaccine. In the study reported
      here two pilot trials have been conducted in Australian sheep flocks, one with a
      virulent form of footrot caused by a single serogroup F, and the other with an
      intermediate form also caused by a single serogroup C. In trial 1 pre-vaccination
      prevalence of clinical footrot in a group of randomly selected animals was 44%.
      This reduced to 2% at 3 months and 0.5% at 4 months, and there were no clinical
      cases at 5 months or at 16 months post-vaccination in the whole flock. Similarly
      in trial 2 pre-vaccination whole flock prevalence was 8.5%, while it was 2% at 3
      months, 0.3% at 6 months and zero at 18 months post-vaccination. Use of flock
      specific monovalent whole cell vaccines over whole flocks for only one season and
      culling of the few non-responders has been a successful approach in eradication
      of the disease from both these flocks. This is the first study to report the
      successful use of specific vaccine for the intermediate form of footrot.

PMID- 18621489
TI  - Microarray-based detection of viruses causing vesicular or vesicular-like lesions
      in livestock animals.
AB  - Definitive diagnosis of vesicular or vesicular-like lesions in livestock animals
      presents challenges both for veterinary clinicians and diagnostic laboratories.
      It is often impossible to diagnose the causative disease agent on a clinical
      basis alone and difficult to collect ample vesicular epithelium samples. Due to
      restrictions of time and sample size, once laboratory tests have ruled out foot
      and-mouth disease, vesicular stomatitis and swine vesicular disease a definitive
      diagnosis may remain elusive. With the ability to test a small quantity of sample
      for a large number of pathogens simultaneously, DNA microarrays represent a
      potential solution to this problem. This study describes the application of a
      long oligonucleotide microarray assay to the identification of viruses known to
      cause vesicular or vesicular-like lesions in livestock animals. Eighteen virus
      isolates from cell culture were successfully identified to genus level, including
      representatives of each foot-and-mouth disease virus serotype, two species of
      vesicular stomatitis virus (VSV), swine vesicular disease virus, vesicular
      exanthema of swine virus (VESV), bovine herpesvirus 1, orf virus, pseudocowpox
      virus, bluetongue virus serotype 1 and bovine viral diarrhoea virus 1. VSV and
      VESV were also identified in vesicular epithelium samples, with varying levels of
      sensitivity. The results indicate that with further development this microarray
      assay could be a valuable tool for the diagnosis of vesicular and vesicular-like
      diseases.

PMID- 18621490
TI  - The changing face of haemolytic disease of the newborn.
AB  - The diagnosis, acute management and follow-up of neonates with haemolytic disease
      of the newborn (HDN) still represents a significant area of activity for
      maternity/neonatal services. ABO incompatability is now the single largest cause
      of HDN in the western world. However, with increasing knowledge at the molecular
      level, and closer liaison between neonatal paediatricians and haematologists, the
      diagnosis of non-immune causes of HDN is increasing. As these conditions have an
      inherited basis and therefore have implications for other family members (or
      future children), it remains a high priority for all neonatal paediatricians to
      achieve an accurate diagnosis in all cases of HDN. As the efficacy of
      phototherapy increases the role of exchange transfusion in acute management is
      rapidly decreasing. This makes gauging the appropriate time to intervene with
      exchange transfusion a difficult clinical decision, and guidelines appropriate to
      the spectrum of contemporary disease are required. In the future intravenous
      immunoglobulin and/or intramuscular metalloporphyrins may further reduce the need
      for exchange transfusion and continue to change the spectrum of HDN faced by
      neonatal paediatricians.

PMID- 18621491
TI  - Application of percolation theory in the study of an extended release Verapamil
      hydrochloride formulation.
AB  - The percolation theory studies the critical points or percolation thresholds of
      the system, where one component of the system undergoes a geometrical phase
      transition, starting to connect the whole system. The objective of the present
      paper was to study the existence of critical points governing the water and drug
      transport inside hydroxypropylmethylcellulose (HPMC) hydrophilic matrix systems
      obtained with different polymer viscosity grades. For this purpose, extended
      release formulations of Verapamil HCl, have been prepared and studied. The
      percolation theory has been applied for the first time to multi-component
      hydrophilic matrices. The materials used to prepare the tablets were Verapamil
      HCl, four different viscosity grades of HPMC, microcrystalline cellulose,
      lactose, magnesium stearate and colloidal silicon dioxide NF. In order to
      estimate the percolation threshold, the behaviour of the kinetic parameters with
      respect to the volumetric fraction of each component at time zero, was studied.
      From the point of view of the percolation theory, the optimum concentration for
      all the studied polymers, to obtain a hydrophilic matrix system for the
      controlled release of Verapamil HCl is higher than 20% (v/v) HPMC. Above 20%
      (v/v) HPMC, an infinite cluster of excipient would be formed, ensuring uniform
      hydration, maintaining integrity of the system and controlling the drug release.

PMID- 18621492
TI  - Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles.
AB  - Injectable biodegradable and biocompatible copolymers of lactic and glycolic acid
      (PLGA) are an important advanced delivery system for week-to-month controlled
      release of hydrophobic drugs (e.g., from biopharmaceutical classification system
      class IV), which often display poor oral bioavailability. The basic principles
      and considerations to develop such microparticle formulations is reviewed here
      based on a comprehensive study of papers and patents from the beginnings of
      hydrophobic drug encapsulation in polylactic acid and PLGA up through the very
      recent literature. Challenges with the diversity of drug properties,
      microencapsulation methods, and organic solvents are evaluated in light of the
      precedence of commercialized formulations and with a focus on decreasing the time
      to lab-scale encapsulation of water-insoluble drug candidates in the early stage
      of drug development. The influence of key formulation variables on final
      microparticle characteristics, and how best to avoid undesired microparticle
      properties, is analyzed mechanistically. Finally, concepts are developed to
      manage the common issues of maintaining sink conditions for in vitro drug release
      assays of hydrophobic compounds. Overall, against the backdrop of an increasing
      number of new, poorly orally available drug entities entering development,
      microparticle delivery systems may be a viable strategy to rescue an otherwise
      undeliverable substance.

PMID- 18621493
TI  - Degradation of biomolecules in artificially and naturally aged teeth:
      implications for age estimation based on aspartic acid racemization and DNA
      analysis.
AB  - Postmortem teeth are the most stable structures, and can be used to gain
      different information (age estimation, genetic data). Over long postmortem
      intervals (PMI), degradation processes may alter the molecular integrity and thus
      affect the reliability of applied molecular methods. Whereas some knowledge on
      the degradation of biomolecules in bone during the PMI exists, data for teeth are
      lacking. In particular, the impact of degradation processes in dentine on age
      estimation based on aspartic acid racemization (AAR) cannot be estimated yet.
      Hence, the molecular stability of both collagen and DNA was analyzed
      systematically, and their impact on the reliability of age estimation based on
      AAR and genetic analyses was checked. Two hundred and ten human and 59 porcine
      teeth were heated (90 degrees C in water) to simulate collagen and DNA
      diagenesis; 14 naturally aged teeth (PMI: 3 days to 1700 years) were analyzed
      comparatively. Peptide patterns of cyanogen bromide (CNBr)-cleaved collagen were
      employed as a new approach to check the collagen integrity. In the same samples,
      collagen yields, amino acid compositions, AAR in different protein fractions, and
      DNA integrity were analyzed. In heated human and porcine teeth the collagen
      content declined during the heating experiment. The amino acid composition in
      human samples was collagen-like until 12 days of heating. In naturally aged
      teeth, the collagen yielded from 9.5 to 15%, and no discrepancy of amino acid
      composition to that of modern collagen was observed. Electrophoresis of CNBr
      peptides showed an altered pattern in experimentally degraded samples from day 10
      on; naturally aged collagen displayed the typical collagen pattern. AAR increased
      in all protein fractions with increasing duration of the heating experiment;
      naturally aged samples displayed a slow accumulation of AAR. DNA degraded
      progressively, and after 32 h of heat exposure no more DNA was detectable,
      whereas the amplification of nuclear and mitochondrial DNA was successful up to
      48 h. STR typing was reliable up to 16 h, and sex determination up to 40 h of
      heat exposure. In naturally aged samples of DNA quality, yield and typing success
      did not correlate with PMI. The data highlight a remarkable stability of collagen
      dental proteins. Within relevant forensic periods a postmortem rise of AAR under
      normal conditions is negligible, and analyses of dental DNA has a high chance to
      be successful. However, after large PMI and/or extreme postmortem conditions age
      estimation based on AAR and genetic analyses lose their reliability.

PMID- 18621494
TI  - Identification of sinicuichi alkaloids in human serum after intoxication caused
      by oral intake of a Heimia salicifolia extract.
AB  - A 26-year-old male came to hospital around midnight complaining about muscle pain
      of the extremities as well as the tongue and slightly raised temperature. He
      reported the intake of an unknown amount of sinicuichi tea he had fermented over
      24 h by adding yeast and sugar. The patient was treated with Vomex A
      (dimenhydrinate) and released from hospital the following afternoon. A blood
      sample taken shortly after submission and a small amount of the used plant
      material were available for analysis. Herbal drugs are widely used as stimulants
      as a legal alternative to illegal psychoactive drugs or in traditional context.
      Among many others like Sassafras officinalis, Salvia divinorum or Ephedra, Heimia
      salicifolia ("sinicuichi"), a species of the lythraceae family, is available via
      several online shops. Brewed up or fermented and consumed, the so-called
      sinicuichi tea may cause exhilarating feelings and an alteration of awareness
      accompanied by bradycardia, relaxation of the muscles and a pleasant faintness.
      Therefore Sinicuichi brew and heimia leaves are widely used for medication by the
      natives of Central and South America. After liquid extraction with acetone five
      different alkaloids were detected in the plant material by LC-MS/MS operated in
      the Q1 scan mode applying a TurboIonSpray source. Subsequently, Product Ion
      Spectra were recorded and after confirming the molecular formula by determining
      the accurate masses, possible structures of H. salicifolia alkaloids were
      assigned. The information of the Product Ion Spectra was then used to set up a
      sensitive multiple reaction monitoring (MRM) method. Applying the MRM method to
      the patient's serum sample after alkaline liquid-liquid extraction all of the
      five heimia alkaloids detected in the plant material were also detected
      qualitatively in the serum extract, confirming the ingestion.

PMID- 18621495
TI  - Non-diagnosed pulmonary hyalinizing granuloma (PHG) as a cause of sudden
      unexpected death.
AB  - Pulmonary hyalinizing granuloma (PHG), a very rare benign tumour of the lungs,
      was first reported in 1977. We present a PHG of a 32-year-old woman from Yemen
      who collapsed 1 day after her arrival in Germany. Tuberculosis was suspected and
      the health authorities nearly closed part of one of the major international
      airports in Europe. However, this drastic measure was avoided by autopsy and a
      correct interpretation of the solid-elastic and well-circumscribed lung tumour as
      not characteristic for tuberculosis. Although the final diagnosis of PHG was only
      achieved after histology, this case strongly illustrates the necessity of a
      profound morphological training of forensic physicians.

PMID- 18621496
TI  - Integration of human papilloma virus type 26 in laryngeal cancer of a child.
AB  - Squamous cell carcinoma (SCC) in larynx is rare with children and adolescents.
      Usually larynx cancer is common with male smokers in the 7th decade. Among
      patients with no history of tobacco and/or alcohol consumption several factors
      have can play a role in the outbreak of laryngeal cancer: such as individual
      predisposition, radiation, gastroesophageal reflux, viral infection, dietary
      factors and environmental influences. In literature only few cases of laryngeal
      cancer with children are reported. Recent studies show that the most frequent
      laryngeal malignancy is the embryonal rhabdomyosarcoma. Besides the recurrent
      respiratory papillomatosis (RRP) based on an infection with human papilloma virus
      (HPV) types 6 and 11 (low risk) and types 16 and 18 (high risk) is known for a
      possible malignant transformation towards a SCC. HPV type 26 is only reported as
      low risk type HPV associated with cervical cancer. Final diagnosis often takes a
      long time. Initial symptoms such as hoarseness, cough or shortness of breath are
      often referred to more typical pediatric diseases or laryngeal development.

PMID- 18621497
TI  - Segawa disease with a novel heterozygous mutation in exon 5 of the GCH-1 gene
      (E183K).
AB  - We report a novel missense mutation in the GCH-1 gene resulting in Segawa
      disease. The patient, a 6-year-old girl, presented with dystonia. Her CSF
      biopterin and neopterin levels were reduced, suggesting Segawa disease. L-dopa
      administration led to clinical improvement. Genetic analysis revealed a missense
      mutation in exon 5 of the GCH-1 gene (E183K). Although dystonia or other movement
      disorders were not identified in her family, this may be explained by the low
      penetrance of Segawa disease.

PMID- 18621498
TI  - A real-time polymerase chain reaction for the detection of Streptococcus
      pneumoniae in blood using a mouse model: a potential new "gold standard".
AB  - Better diagnostics for pneumococcal disease are urgently needed. In a murine
      model, real-time polymerase chain reaction was superior to conventional culture
      in detecting pneumococcus in blood, particularly in early disease and after
      antibiotic administration, and could distinguish between commensalism and
      infection.

PMID- 18621499
TI  - Cocirculation of genotypes D4 and D6 in Greece during the 2005 to 2006 measles
      epidemic.
AB  - One of World Health Organization's proposed methods for the establishment of
      measles surveillance worldwide, to achieve the elimination of measles virus by
      2010, is the genetic characterization of measles wild-type virus strains. In this
      study, 34 measles virus strains, isolated from clinical samples during the 2005
      to 2006 measles outbreak in Greece, were genotyped and studied in terms of
      nucleotide variation and phylogeny. Interestingly, the cocirculation of 2
      different genotypes, namely, D6 and D4, was revealed. In fact, the D4 genotype
      has never been previously reported in Greece. Finally, although the D4 Greek
      strains possessed identical nucleotide sequences, the D6 isolates segregated into
      3 distinct subgroups, 2 of which differed genetically and phenotypically from all
      GenBank deposited measles sequences. It is, thus, important to continue the
      epidemiologic surveillance of measles in Greece to aid future studies of measles
      transmission, monitor the effectiveness of measles immunization, and eventually
      document the elimination of the virus in our country.

PMID- 18621500
TI  - Design and implementation of a protocol for the detection of Legionella in
      clinical and environmental samples.
AB  - Our laboratory has developed a novel real-time polymerase chain reaction (PCR)
      assay for the detection of Legionella pneumophila and differentiation from other
      Legionella spp. in clinical and environmental samples. The 23S rRNA gene was used
      as a target to detect all Legionella spp., and the mip gene was targeted for the
      specific detection of L. pneumophila in this multiplex Taqman real-time PCR
      assay. The 23S rRNA gene is a novel target for Legionella testing; it detects all
      species and serogroups of Legionella without the contamination issues that
      accompany the use of the 16S rRNA gene as a target. This assay provides an
      analytical sensitivity of <1 colony-forming unit and a specificity of 100%.
      Because culture is important and provides a means for molecular typing via pulsed
      field gel electrophoresis (PFGE), we developed a testing algorithm that includes
      both the new real-time PCR assay and culture for clinical and environmental
      samples and applied this algorithm during a period of 3 years. Of the 64 clinical
      samples received by our laboratory for Legionella testing during this period, PCR
      was found to be an essential diagnostic tool because only 13.3% (2/15) clinical
      samples that were determined to be L. pneumophila were detected by culture during
      this period. Of the 276 environmental samples received for Legionella testing
      during this period, 140 were found to be positive for L. pneumophila. Of these
      140 samples, 69.3% were detected by both PCR and culture methods, 29.3% were
      positive by PCR alone, and 1.4% were positive by culture methods alone. We feel
      these results indicate that our algorithm, including both PCR and culture, should
      be used for environmental samples. Among both the clinical and environmental
      Legionella samples identified by PCR, a subset was not suitable for culture
      because of issues of lengthy transport, antimicrobial treatment, or bacterial
      overgrowth. Samples like these are commonly submitted to our laboratory, so the
      use of our testing algorithm combining these methods is critical. We conclude
      that molecular and culture methods must be used in combination to provide the
      best and most comprehensive approach to laboratory detection and investigation of
      legionellosis.

PMID- 18621501
TI  - Integrating diabetes self-management with the health goals of older adults: a
      qualitative exploration.
AB  - OBJECTIVE: This study investigates the life and health goals of older adults with
      diabetes, and explores the factors that influence their diabetes self-management.
      METHODS: Qualitative in-depth interviews were conducted with 24 older adults with
      diabetes and other morbid conditions and/or their caregivers, when appropriate.
      RESULTS: Participants' provided a consistent set of responses when describing
      life and health goals. Participants described goals for longevity, better
      physical functioning, spending time with family, or maintaining independence.
      Diabetes discordant conditions, but not diabetes, were seen as barriers to life
      goals for participants with functional impairments. Functionally independent
      participants described additional health goals that related to diabetes self
      management as diabetes was seen often a barrier to life goals. Caregivers, co
      morbid conditions, denial and retirement were among the factors that influenced
      initiation of diabetes self-management. CONCLUSION: Participants endorsed health
      goals and diabetes self-management practices that they believed would help them
      accomplish their life goals. Functional capabilities and social support were key
      factors in the relationship between diabetes self-management and their broader
      goals. PRACTICE IMPLICATIONS: When planning diabetes treatments, clinicians,
      patients and caregivers should discuss the relationship between diabetes self
      management and health and life goals as well as the affects of functional
      limitations and caregiver support.

PMID- 18621502
TI  - Barriers to fertility preservation among pediatric oncologists.
AB  - OBJECTIVE: Limited research has been conducted on the extent to which fertility
      preservation is discussed by pediatric oncologists with patients and less is
      known about the discussion content. This study sought to examine factors that may
      influence the discussion with pediatric cancer patients and families. METHODS:
      Qualitative data were collected using open-ended, in-depth interviews with 24
      pediatric oncologists in Florida at 13 children's cancer centers, representing
      87% of the centers in the state. RESULTS: Providers practiced between 0.5 and 35
      years, treated most types of pediatric cancers, and most were board certified in
      pediatric hematology/oncology. The main factors associated with a discussion of
      fertility preservation options were: (1) physician factors that contribute to
      communication issues with FP discussion (e.g., awareness and sense of comfort in
      discussing issues, perceptions of the priority); (2) parent factors (e.g.,
      receptiveness and cultural background); (3) patient factors (e.g., receptiveness
      and age); and (4) institutional factors (e.g., referral sites and practice
      guidelines). CONCLUSIONS: Pediatric oncologists may benefit from education about
      fertility preservation options for pediatric cancer patients, particularly
      females. PRACTICE IMPLICATIONS: Training on how to address parents' and patients'
      emotions, culture, and other factors may also promote the discussion. Although
      guidelines have been established, barriers related to availability and
      affordability of resources must also be addressed.

PMID- 18621503
TI  - [Thrombocytopenia during pregnancy: from etiologic diagnosis to therapeutic
      management].
AB  - Thrombocytopenia complicates 10% of all pregnancies. It has many potential
      causes, but three are responsible for almost all cases: incidental gestational
      thrombocytopenia (IGT) (74%), preeclampsia and HELLP (hemolysis, elevated liver
      function tests, low platelet count) syndrome (21%) and immune thrombocytopenic
      purpura (ITP) (4%). Although there is no risk of maternal or fetal hemorrhage
      with IGT, a benign disorder, preeclampsia, HELLP syndrome and ITP expose mother
      and child to potentially life-threatening complications. Other rare causes are
      also associated with severe complications: thrombotic thrombocytopenic purpura,
      hemolytic and uremic syndrome, disseminated intravascular coagulation and von
      Willebrand disease type IIB. Because risks for mother and child vary so greatly
      according to the cause of thrombocytopenia, an accurate etiologic diagnosis is
      essential to ensure optimal therapeutic management.

PMID- 18621504
TI  - The role of toxicology to characterize biomarkers for agrochemicals with
      potential endocrine activities.
AB  - The paper discusses current knowledge and possible research priorities on
      biomarkers of exposure, effect and susceptibility for potential endocrine
      activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates,
      triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals
      highlights the need to assess internal exposure of animals or humans, which is
      the most relevant exposure measure for hazard and risk estimation; however,
      exposure data should be integrated by early indicators predictive of possible
      health effects, particularly for vulnerable groups such as mother-child pairs.
      Research need include: non-invasive biomarkers for children biomonitoring; novel
      biomarkers of total exposure to measure whole endocrine disrupter-related burden;
      characterization of biomarkers of susceptibility, including the role of markers
      of nutritional status; anchoring early molecular markers to established
      toxicological endpoints to support their predictivity; integrating "omics"-based
      approaches in a system-toxicology framework. As biomonitoring becomes
      increasingly important in the environment-and-health scenario, toxicologists can
      substantially contribute both to the characterization of new biomarkers and to
      the predictivity assessment and improvement of the existing ones.

PMID- 18621505
TI  - Chronic enteropathy and feeding in children: an update.
AB  - Enteropathy defines abnormalities of the small intestinal mucosa of various
      etiologies in which nutrition has a causal or a therapeutic role. Breast milk is
      the gold-standard feeding during infancy for optimal nutrition in health and the
      majority of diseases. Therapeutic formulae have decreased the need for enteral or
      parenteral support. Gastrointestinal infections are worldwide the most frequent
      cause of enteropathy by increasing mucosal permeability, local expression of
      costimulatory molecules allowing antigen penetration in the mucosa, and T-cell
      activation leading sometimes to disruption of oral tolerance. Concomitant
      malnutrition impairs not only the immunologic response but also the recovery of
      damaged mucosa with secondary intestinal and pancreatic enzymatic reductions.
      Optimal nutritional rehabilitation is the cornerstone of the management of
      persisting diarrhea. Celiac disease and cow's milk protein allergy are examples
      of chronic enteropathy. Multiple food allergies, even during breast-feeding, are
      increasingly reported due to an impaired development of oral tolerance. The
      dietary approach to allergic disease is currently evolving from passive allergen
      avoidance to active modulation of the immune system to (re)establish tolerance.
      The gastrointestinal flora provides maturational signals for the lymphoid tissue,
      improves balance of inflammatory cytokines, reduces bacterial invasiveness and
      dietary antigen load, and normalizes gut permeability. The clinical effects of
      nucleotides and zinc merit further clinical evaluation. Major attention has
      recently focused on the immune effects of dietary lipids in terms of possible
      prevention of allergic sensitization by downregulating inflammatory response and
      protecting the epithelial barrier and host-microbe interactions modifying the
      adherence of microbes to the mucosa.

PMID- 18621506
TI  - Expression of cIAP-1 correlates with nodal metastasis in squamous cell carcinoma
      of the tongue.
AB  - Cellular inhibitor-of-apoptosis protein 1 (cIAP-1) is a member of the inhibitor
      of- apoptosis protein family, which predominantly regulates apoptosis. It has
      been suggested that expression of cIAP-1 correlates with certain
      clinicopathological features. The possible significance of cIAP-1 expression in
      cervical lymph node metastasis of tongue squamous cell carcinoma (SCC) is
      investigated. Seventy-five tongue SCCs were analyzed by immunohistochemistry.
      cIAP-1 immunoreactivity patterns were nuclear in 38 (51%), cytoplasmic in 47
      (63%), and concurrent in 37 (49%) cases. Nuclear, cytoplasmic and concurrent cIAP
      1 immunoreactions were significantly correlated with lymph node metastasis in
      tongue SCCs (P=0.0011, 0.0012, and 0.0006, respectively). The cleaved caspase-3,
      which is a marker of tumor apoptosis, and Ki-67 index, which is a marker of tumor
      proliferation, were immunohistochemically examined in 21 tongue SCCs with
      concurrent nuclear and cytoplasmic cIAP-1 expression and with metastasis, and in
      23 tongue SCCs without concurrent nuclear and cytoplasmic cIAP-1 expression and
      without metastasis. Concurrent cIAP-1 expression was inversely correlated with
      caspase-3 (P=0.0066), but was positively correlated with Ki-67 expression
      (P=0.0028). The mode of invasion was associated with lymph node metastasis
      (P=0.014) and differentiation (P=0.013), but was not correlated with cIAP-1
      expression. There was no statistically significant correlation between nuclear or
      cytoplasmic cIAP-1 expression and the clinicopathological factors of gender, age,
      clinical stage or differentiation. These results suggest that both patterns of
      cIAP-1 are useful markers for predicting cervical lymph node metastasis in tongue
      SCC.

PMID- 18621507
TI  - Postoperative stability of bimaxillary surgery in Class III patients with
      mandibular protrusion and mandibular deviation: a frontal cephalometric study.
AB  - The aims of this study into bimaxillary surgery were to investigate and compare
      the postoperative stability of deviated side (lengthened side) and non-deviated
      side (shortened side), the effect of the type of surgery performed in the
      mandible, and the changes in signs and symptoms of temporomandibular joint (TMJ)
      disorders before and after surgery. The sample consisted of 31 Class III patients
      in whom imbalance between the maxilla and the mandible were corrected by Le Fort
      I osteotomy combined with bilateral intraoral vertical ramus osteotomy (BIVRO
      group, n=9), bilateral sagittal split ramus osteotomy (BSSRO group, n=10), or
      IVRO and SSRO (IVRO+SSRO group, n=12). IVRO+SSRO and BIVRO are more effective in
      improving TMJ signs and symptoms. There was no significant post-surgical
      difference between deviated and non-deviated sides in any group. BIVRO and BSSRO
      showed excellent post-surgical stability on both sides; less was found in the
      IVRO+SSRO group. The IVRO+SSRO group showed greater transverse displacement in
      menton point than the BIVRO group. In conclusion, after bimaxillary surgery and
      in asymmetric patients there were no differences between deviated and non
      deviated sides, BIVRO and BSSRO appear to be more stable than IVRO+SSRO.

PMID- 18621508
TI  - Pharmacokinetics/pharmacodynamics of antibacterials in the Intensive Care Unit:
      setting appropriate dosing regimens.
AB  - Patients admitted to Intensive Care Units (ICUs) are at very high risk of
      developing severe nosocomial infections. Consequently, antimicrobials are among
      the most important and commonly prescribed drugs in the management of these
      patients. Critically ill patients in ICUs include representatives of all age
      groups with a range of organ dysfunction related to severe acute illness that may
      complicate long-term illness. The range of organ dysfunction, together with drug
      interactions and other therapeutic interventions (e.g. haemodynamically active
      drugs and continuous renal replacement therapies), may strongly impact on
      antimicrobial pharmacokinetics in critically ill patients. In the last decade, it
      has become apparent that the intrinsic pharmacokinetic (PK) and pharmacodynamic
      (PD) properties are the major determinants of in vivo efficacy of antimicrobial
      agents. PK/PD parameters are essential in facilitating the translation of
      microbiological activity into clinical situations, ensuring a successful outcome.
      In this review, we analyse the typical patterns of antimicrobial activity and the
      corresponding PK/PD parameters, with a special focus on a PK/PD dosing approach
      of the antimicrobial agent classes commonly utilised in the ICU setting.

PMID- 18621509
TI  - A regulatory Apologia--a review of placebo-controlled studies in regulatory
      submissions of new-generation antidepressants.
AB  - Data on percentage of patients experiencing a relevant response (>50% reduction
      of the baseline Hamilton Depression Scale (HAMD) score), average baseline
      severity and sample size were retrieved for all placebo-controlled studies in
      regulatory submissions of SSRIs and SNRIs between 1984 and 2003. Overall there
      was 16%-units (95% CI: 12; 20) more responders on active drug compared to
      placebo. There was no evidence of a diminishing magnitude of effect with lower
      severity at baseline. With one exception significant differences varying between
      13.5 and 19.3%-units were demonstrated for the individual antidepressants.
      Statistically significant mean differences versus placebo in change in HAMD are
      not a proper basis for evaluation of clinical relevance and are not sufficient
      for approval. Differences in the percentage of patients experiencing a clinically
      relevant response should also be demonstrated. In this respect, the approved
      SSRIs and SNRIs were found superior to placebo, independent of severity of
      depression.

PMID- 18621510
TI  - Spectral properties and inclusion of 3-(4'-dimethylaminophenyl)-1-(2-furanyl)prop
      2-en-1-one in organized media of micellar solutions, beta-cyclodextrin and
      viscous medium.
AB  - On the line of a previous work on the spectral properties of some of heteroaryl
      chalcone, the absorption and fluorescence emission spectral properties of 3-(4'
      dimethylaminophenyl)-1-(2-furanyl)prop-2-en-1-one (DMAFP), have been investigated
      in organized media of aqueous micellar and beta-cyclodextrin (beta-CD) solutions.
      While the absorption spectra are less sensitive to the nature of the added
      surfactant or beta-CD, the characteristics of the intramolecular charge transfer
      (ICT) fluorescence are highly sensitive to the properties of the medium. The ICT
      maximum is strongly blue-shifted with a great enhancement in the fluorescence
      quantum yield on adding micellar or beta-CD. This indicates the solubilization of
      DMAFP in the micellar core and formation of an inclusion complex with beta-CD.
      The critical micelle concentrations (CMC) as well as the polarity of the micellar
      core of SDS, CTAB and TX-100 have been determined. The CMC values are in good
      agreement with the reported values while the polarity is lower indicating that
      DMAFP molecules are incorporated in the micellar core not at the micellar
      interface. The inclusion constants of binding of DMAFP in micellar or beta-CD
      have been also determined. The thermodynamic parameters of formation of DMAFP:CD
      inclusion complex have been calculated from the temperature dependence of the
      fluorescence spectra of the formed complex. The highly negative value of
      formation entropy (DeltaS=-98.0Jmol(-1)K(-1)) reflects the high restrictions
      imposed on the movement of both the host and included guest molecules which is
      consistent with the increase of the fluorescence yield and blue shift of the
      fluorescence maximum.

PMID- 18621511
TI  - Degradation of liposome cluster caused by the interaction with endocrine
      disrupting chemicals (EDCs).
AB  - The interaction between endocrine disrupting chemicals (EDCs) and liposome
      clusters was investigated using UV-vis spectroscopy and observed by microscope.
      Since liposome clusters are composed of small unilamellar liposomes and membrane
      proteins, they are regarded as a model of plasma membranes. The size of each
      cluster was 10microm in diameter. UV-vis spectroscopy of liposome clusters showed
      an apparent absorption at 300nm which was affected by the interaction with EDCs.
      Four EDCs caused an alteration in absorption in a concentration-dependence manner
      between 0.1 and 10ppm (i.e. 0.1-10mg/l). Microscopic observation showed that the
      effect was caused by the degradation of liposome clusters while degradation was
      induced by the interaction; liposome was broken down by EDCs. This report
      suggests that the liposome cluster can be applied for universal detection of EDCs
      based on the interaction between a plasma membrane model and EDCs.

PMID- 18621512
TI  - Chitosan and a modified chitosan as agents to improve performances of
      mucoadhesive vaginal gels.
AB  - New mucoadhesive formulations were designed and studied in order to improve local
      vaginal therapy by increasing formulation retention prolonging thus drug-mucosa
      contact time. Some gels were prepared using hydroxyethylcellulose (HEC) alone or
      mixed with chitosan (CS) or its derivative 5-methyl-pyrrolidinone-chitosan (MPCS)
      and were loaded with the antibacterial metronidazole (MET) (0.75%). All
      formulations showed pseudoplastic flow and viscosity increase was observed
      proportionally to chitosan content (CS>MPCS). Prepared gels showed better
      extrusion properties (yield stress) than market formulation Zidoval. Mucoadhesion
      force studies permitted to point out that: (i) CS decreases mucoadhesion force;
      (ii) MPCS addition increases the mucoadhesion force at high percentage; (iii) all
      gels containing chitosan showed better mucoadhesive performances than Zidoval.
      Gels containing MPCS showed higher and faster drug release than those containing
      CS. All the preparations were able to release higher drug amounts if compared to
      market formulation. In conclusion MPCS improved gel characteristics in terms of
      mucoadhesion force, rheological behaviour and drug release pointing out that this
      modified chitosan is very suitable to obtain manageable and more acceptable
      vaginal formulation.

PMID- 18621513
TI  - Towards a biosensor immunoassay of protein-bound isopeptides in human plasma.
AB  - This study demonstrates that synthetic isopeptides formed on BSA can be
      quantitatively analyzed by a surface plasmon resonance-based biosensor method. A
      monoclonal IgM antibody 81D4, that reacts with the synthetic isopeptide and also
      with the natural isopeptide cross-link in D-dimer (but not with its non-cross
      linked fibrin monomer), was covalently immobilized to a carboxymethylated dextran
      surface, a CM5 surface. Its immunocapturing efficiency was found to be good. The
      affinity of the interaction between the monoclonal 81D4 and the synthetic
      isopeptide was estimated to approximately 4x10(-7)M. Good reactivity was also
      observed when human plasma spiked with this isopeptide was used as test solution.
      Cross-linked D-dimer in the plasma of patients is a marker of disseminated
      intravascular coagulation (DIC) which occurs late in sepsis. This biosensor
      method has the potential to be developed into a rapid sensitive assay for
      measuring the level of natural isopeptide cross-links in proteins in the plasma
      of patients with a suspected diagnosis of sepsis.

PMID- 18621514
TI  - Gelation of charged bio-nanocompartments induced by associative and non
      associative polysaccharides.
AB  - Vesicles composed of sodium oleate (NaO) and monoolein (MO) are adequate
      candidates for drug nanoencapsulation and controlled release due to their
      stability and perceived biocompatibility. The object of the present study is to
      design hydrogels based on those anionic vesicles and polymers of both non
      associative and associative type. The selected macromolecules were k-carrageenan
      (KC), carboxymethyl cellulose (CMC) and hydrophobically modified carboxymethyl
      cellulose (HMCMC). While the polymer-vesicle association was probed by rheology,
      the influence of the polymer on the vesicle stability was monitored by cryo-TEM
      and calorimetric measurements. The effects of the polymer on the rheological
      properties of surfactant aggregate solutions clearly depend on the polymer type:
      the storage moduli of the polymer-vesicle mixtures, compared to the vesicles
      alone, increases around 2 orders of magnitude if the polymer is non-associative
      and 4 orders of magnitude if the macromolecule is of associative type. As the
      vesicles are added, the non-associative polymer networks tend to be disrupted,
      while the networks formed by associative polymer get more robust. These
      observations can be explained by fundamental changes in electrostatic/hydrophobic
      interactions: vesicles entrapped in KC networks convert the polysaccharide in a
      highly charged entity and favor high electrostatic repulsions between the chains;
      this encourages network collapse. The opposite picture is experienced in HMCMC
      systems, i.e., such network is stabilized by the presence of vesicles. This is
      ascribed to the enhanced hydrophobic association, compensating the electrostatic
      repulsions between vesicles and polymer chains.

PMID- 18621515
TI  - Influence of dipalmitoylphosphatidylcholine on the dissolution of Brazilian
      chrysotile.
AB  - It is known that Brazilian chrysotile is rapidly removed from the lungs, but
      quantitative studies about the influence of lung surfactants on chrysotile
      dissolution have not been investigated. In this work, the chemical behavior of
      chrysotile and its dissolution in the presence of dipalmitoylphosphatidylcholine
      (DPPC) were investigated in physiological conditions. The dissolution was
      investigated through quantification of magnesium and silicon released by
      chrysotile. At 37 degrees C, the magnesium concentration is similar to control
      (without DPPC), which is about 2.0x10(-4)molL(-1), meaning that the dissolution
      process is not affected by the presence of this surfactant. The same was observed
      for silicon. The silicon concentration released by chrysotile is similar in all
      media tested. It is known that the dissolution mechanisms of brucite and
      tridymite layers are different. From our results, we propose that under
      physiological conditions, the mechanism of brucite dissolution is based on its
      interaction with hydrogen ions and that the mechanism of tridymite dissolution is
      based on a hydrolysis process.

PMID- 18621516
TI  - Raman and thermal analysis of indomethacin/PVP solid dispersion enteric
      microparticles.
AB  - Indomethacin (IMC) and three types of poly-(vinylpyrrolidone) (PVP 12PF, PVP K30
      and PVP K90) were studied in the form of solid dispersion, prepared with the
      solvent evaporation method, by spectroscopic (Raman, FT-IR, X-ray diffraction),
      thermal (differential scanning calorimetry, thermogravimetry, hot-stage
      microscopy), fractal and image analysis. Raman and FT-IR micro-spectroscopy
      indicated the occurrence of drug/polymer interaction and the presence of an
      amorphous form of IMC, as also resulting from X-ray diffractometry. Hot-stage
      microscopy suggested that the interaction between IMC and the polymer occurring
      on heating of a physical mixture, is common to other acidic compounds and causes
      a depression of the temperature of the appearance of a molten phase. Co
      evaporated particles were coated by spray-congealing process with molten stearic
      acid for gastroprotection, but also for stabilization of the amorphous structure
      of the drug: the final particles were spherically shaped. Dissolution tests
      carried out on the final microparticles showed that the coating with stearic acid
      prevents IMC release at acidic pH and also protects against recovery of the IMC
      crystallinity, at least after 9 months of aging: the extent and mode of the
      release, before and after aging, overlap perfectly. The test revealed a notable
      improvement of the drug release rate from the solid dispersion at suitable pH,
      with respect to pure IMC. The comparison of the present solid dispersion with
      IMC/PVP (surface) solid dispersion obtained by freeze-drying of an aqueous
      suspension, where IMC maintained its crystalline state, revealed that there was
      no difference concerning the release rate, but suggested a superior quality of
      this last process as a mean of improving IMC availability for the easiness of
      preparation and stability, due to the absence of the amorphous state of the drug,
      as a possible instability source of the system. Finally, the coating with stearic
      acid is discussed as a determining process for the practical application of solid
      dispersions.

PMID- 18621517
TI  - Cyclin A expression is associated with apoptosis and mitosis in murine 3
      methylcholanthrene-induced fibrosarcomas.
AB  - The chemical carcinogen MCA induces fibrosarcoma and tissue damage at the
      injection site. Despite the importance of ROS in the development of cancer,
      little is known about the pattern of expression of ROS in MCA-induced
      fibrosarcomas. To gain some insight into the biological significance of iNOS and
      Cu/Zn-SOD, comparative immunohistochemical analyses were performed to
      characterize their expression in MCA-induced fibrosarcomas. Cyclin A is
      overexpressed in various tumors, but its expression in MCA-induced fibrosarcoma
      in mice and its correlation to mitosis and apoptosis are unclear. The presence of
      apoptotic cell death was evaluated using the TUNEL method and findings were
      compared with cyclin A expression and mitotic count of fibrosarcomas.
      Subcutaneous application of MCA caused fibrosarcoma development in 14 of 20 mice
      (70%) in 26 weeks. Limited cytoplasmic Cu/Zn-SOD and iNOS immunostainings were
      detected in 13 of 14 and 9 of 14 tumors with median immunoreactive scores of 2
      and 1, respectively. Prominent nuclear cyclin A immunostaining and TUNEL-positive
      reactions were seen in all the fibrosarcoma cases. Cyclin A immunoreaction
      significantly correlated with the TUNEL index (P<0.01) and MC (P<0.001). The
      present findings show a low level of iNOS expression in neoplastic cells
      indicating limited synthesizing capacity of tumor cells. Limited Cu/Zn-SOD
      reaction could be associated with an imbalance in between pro-oxidant/antioxidant
      levels. Furthermore, it was shown that cyclin A is overexpressed in MCA-induced
      fibrosarcomas and possibly plays a significant role in the pathogenesis of
      fibrosarcomas. Cyclin A could be useful for detecting the S phase of the cell
      cycle and could also indicate that cyclin A may induce S phase arrest associated
      with apoptosis in the MCA-induced fibrosarcomas.

PMID- 18621519
TI  - Use of 6-min and 12-min walking test for assessing the efficacy of formoterol in
      COPD.
AB  - Exercise tolerance is an important outcome measure in patients with COPD, mostly
      because there is evidence that exercise testing is superior to other functional
      measurements obtained at rest in demonstrating the positive effect of a specific
      intervention. We assessed the effect of a 5-day treatment with formoterol 12
      microg twice daily on lung function, exercise capacity and dyspnea in 22 stable
      COPD patients, and compared 6-MWT with 12-MWT in evaluating formoterol efficacy.
      All subjects entered a crossover design. They underwent 6-MWT or 12-MWT in a
      randomised order and soon after started the 5-day treatment. After a 3-day
      washout, patients who had first performed 6-MWT, underwent 12-MWT, and the
      contrary. Formoterol induced a progressively significant increase in pre-drug
      FEV1 and IC and also significant changes in these parameters 2 h after its
      inhalation at each test day. Moreover, it increased the walked distance by 53.6 m
      at the end of 6-MWT and 59.9 m at the end of 12-MWT. Formoterol also induced a
      significant change in Borg score for dyspnea caused by the 6-MWT when compared
      with the pre-treatment values, whereas it significantly changed dyspnea induced
      by 12-MWT only after the first dose. Our study not only strengthens the
      importance of walking tests as a useful tool for evaluating the impact of a
      bronchodilator on some COPD patient-centred outcomes, but also indicates that 6
      MWT seems to be a more appropriate instrument than 12-MWT for assessing the
      exercise response to a bronchodilator in COPD.

PMID- 18621518
TI  - Assessment of current practice in the diagnosis and therapy of idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: The consensus statement on the Diagnosis and Therapy of Idiopathic
      Pulmonary Fibrosis (IPF) formulated by the American Thoracic Society/European
      Respiratory Society (ATS/ERS) was published in 2000. Acceptance and
      implementation of these guidelines have not been assessed. We surveyed the
      fellows of the American College of Chest Physicians (FCCP) to establish current
      practice patterns regarding the diagnosis and therapy of IPF. METHODS: We
      electronically distributed a 32-item questionnaire to all 6443 pulmonary medicine
      board-certified Fellows of the American College of Chest Physicians. The response
      rate was 13%. Demographic characteristics were similar between respondents and
      non-respondents. RESULTS: Seventy-two percent of respondents were familiar with
      the ATS/ERS consensus statement and 63% found it clinically useful. However, a
      similar number of respondents indicated that an update is needed. Bronchoscopy
      and surgical lung biopsy are used infrequently. Forty-five percent of pulmonary
      physicians advocate providing only supportive care for patients outside of
      clinical trials. If pharmacological therapy is recommended, prednisone (either
      alone or in combination with azathioprine) or off-label agents are preferentially
      prescribed. Despite physician awareness (79%) of clinical trials, interested
      patients are not consistently referred (54%). A majority of respondents (61%)
      felt that lung transplantation represents the only effective therapy for IPF, and
      86% refer their patients to lung transplant centers. CONCLUSIONS: There is
      substantial variability among pulmonary physicians in the diagnosis and
      management of IPF. This may, in part, reflect the current lack of effective
      pharmacologic therapy. Updated practice guidelines are needed for the diagnosis
      and therapy of IPF.

PMID- 18621520
TI  - Perspectives for integrated municipal solid waste management in Thessaloniki,
      Greece.
AB  - Local authorities need updated and reliable data on the quantity and the quality
      of the waste generated in their area, in order to establish an integrated solid
      waste management system capable of fulfilling regional and national waste
      management targets. This paper presents information about the quantity and the
      characteristics of the municipal solid waste generated in Thessaloniki, which is
      the second largest city in Greece. It is based on the results of three research
      programs investigating the evolution of municipal solid waste. The investigations
      were carried out over the last 20 years at the landfill of Thessaloniki by the
      same research group using statistically acceptable practices for sampling and
      hand sorting. The results show a great increase in the incoming quantities during
      the last years and a significant increase of the per capita generation. There is
      also a significant change in the composition, demonstrated mainly by a decrease
      in the organic fraction followed by an increase of packaging materials (paper and
      plastic).

PMID- 18621521
TI  - Microbial fuel cell biosensor for in situ assessment of microbial activity.
AB  - Microbial fuel cell (MFC)-based sensing was explored to provide useful
      information for the development of an approach to in situ monitoring of substrate
      concentration and microbial respiration rate. The ability of a MFC to provide
      meaningful information about in situ microbial respiration and analyte
      concentration was examined in column systems, where Geobacter sulfurreducens used
      an external electron acceptor (an electrode) to metabolize acetate. Column
      systems inoculated with G. sulfurreducens were operated with influent media at
      varying concentrations of acetate and monitored for current generation. Current
      generation was mirrored by bulk phase acetate concentration, and a correlation
      (R(2)=0.92) was developed between current values (0-0.30 mA) and acetate
      concentrations (0-2.3 mM). The MFC-system was also exposed to shock loading
      (pulses of oxygen), after which electricity production resumed immediately after
      media flow recommenced, underlining the resilience of the system and allowing for
      additional sensing capacity. Thus, the electrical signal produced by the MFC
      system provided real-time data for electron donor availability and biological
      activity. These results have practical implications for development of a
      biosensor for inexpensive real-time monitoring of in situ bioremediation
      processes, where MFC technology provides information on the rate and nature of
      biodegradation processes.

PMID- 18621522
TI  - N-(thiazol-2-yl)-2-thiophene carboxamide derivatives as Abl inhibitors identified
      by a pharmacophore-based database screening of commercially available compounds.
AB  - Suggestions derived from a previous ligand-based ligand design approach and
      docking calculations aimed at finding compound with affinity toward Abl and
      molecular scaffolds previously untested as Abl inhibitors, led to the
      identification of commercially available N-(thiazol-2-yl)-2-thiophene carboxamide
      derivatives with affinity in a cell-free assay up to low nanomolar
      concentrations, significantly enhanced with respect to that of their parent
      compounds previously reported. In particular, among compounds of the Asinex
      database, molecular docking simulations guided the choice of high-affinity
      ligands, predicting their binding mode and their interaction pattern with the Abl
      catalytic binding site. Moreover, affinity of the new compounds was also
      rationalized in terms of their interactions with the enzyme.

PMID- 18621523
TI  - Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid
      based analogs of GW 4064.
AB  - Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements
      were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR
      agonist with improved developability parameters relative to 1a. Analog 1b also
      reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

PMID- 18621524
TI  - The identification of potent, selective and CNS penetrant furan-based inhibitors
      of B-Raf kinase.
AB  - Modification of the potent imidazole-based B-Raf inhibitor SB-590885 resulted in
      the identification of a series of furan-based derivatives with enhanced CNS
      penetration. One such compound, SB-699393 (17), was examined in vivo to challenge
      the hypothesis that selective B-Raf inhibitors may be of value in the treatment
      of stroke.

PMID- 18621525
TI  - Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy
      pyrimidines.
AB  - Reaction of 6a-f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine
      yielded 7a-f in excellent yield. The newly synthesized heterocycles were
      characterized by IR, (1)H NMR, and mass spectral data. Compounds 7a-f was
      screened for their anti-inflammatory activity and were compared with standard
      drugs. Of the compounds studied, the compound 7e showed more potent activity than
      the standard drugs at all doses tested.

PMID- 18621526
TI  - Design and synthesis of regioisomerically pure unsymmetrical xanthene derivatives
      for staining live cells and their photochemical properties.
AB  - We have demonstrated the synthesis of regioisomerically pure unsymmetrical
      xanthene derivatives consisting of three units which can be independently
      modified to control their physical properties. The photochemical properties of
      the synthetic unsymmetrical xanthene derivatives were investigated in solution by
      UV-vis absorption and fluorescence measurements, and their cell imaging
      properties were examined by confocal laser-scanning microscopy.

PMID- 18621527
TI  - Benzodiazepine ligands can act as allosteric modulators of the Type 1
      cholecystokinin receptor.
AB  - The cholecystokinin (CCK(1)) receptor is a G protein-coupled receptor important
      for nutrient homeostasis. The molecular basis of CCK-receptor binding has been
      debated, with one prominent model suggesting occupation of the same region of the
      intramembranous helical bundle as benzodiazepines. Here, we used a specific assay
      of allosteric ligand interaction to probe the mode of binding of devazepide, a
      prototypic benzodiazepine ligand. Devazepide elicited marked slowing of
      dissociation of pre-bound CCK, only possible through binding to a topographically
      distinct allosteric site. This effect was disrupted by chemical modification of a
      cysteine in the benzodiazepine-binding pocket. Application of an allosteric model
      to the equilibrium interaction between a series of benzodiazepine ligands and CCK
      yielded quantitative estimates of each modulator's affinity for the allosteric
      site, as well as the degree of negative cooperativity for the interaction between
      occupied orthosteric and allosteric sites. The allosteric nature of
      benzodiazepine binding to the CCK(1) receptor provides new opportunities for
      small molecule drug development.

PMID- 18621528
TI  - Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine as selective
      noradrenaline reuptake inhibitors: Reducing P-gp mediated efflux by modulation of
      H-bond acceptor capacity.
AB  - Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine are disclosed as a
      new series of noradrenaline reuptake inhibitors (NRI). Carboxamide 9e, carbamate
      11b and sulfonamide 13a were identified as potent NRIs with excellent selectivity
      over SRI and DRI, good in vitro metabolic stability and weak CYP inhibition.
      Carbamate 11b demonstrated superior transit performance in MDCK-mdr1 cell lines
      with minimal P-gp efflux which was attributed to reduced HBA capacity of the
      carbamate group. Evaluation in vivo, in rat microdialysis experiments, showed 11b
      increased noradrenaline levels by 400% confirming good CNS penetration.

PMID- 18621529
TI  - Synthesis of hydantoin analogues of (2S,3R,4S)-4-hydroxyisoleucine with
      insulinotropic properties.
AB  - The first synthesis of an optically pure (2R,3R,4S)-hydantoin 2, analogue of
      (2S,3R,4S)-4-hydroxyisoleucine, was achieved in two steps in un-optimized 35%
      overall yield from previously reported aldehyde synthon 1. (2R,3R,4S)-Hydantoin
      is stable at acidic pH. This solves the major drawback of (2S,3R,4S)-4
      hydroxyisoleucine that easily cyclizes into inactive lactone. Furthermore,
      (2R,3R,4S)-hydantoin stimulates the insulin secretion by 150% at 25microM
      compared with 4-hydroxyisoleucine and insulin secretagogue drug repaglinide. In
      view of its stability and biological activity, (2R,3R,4S)-hydantoin represents a
      good candidate for type-2 diabetes management and control.

PMID- 18621531
TI  - Skin temperature as a noninvasive marker of haemodynamic and perfusion status in
      adult cardiac surgical patients: an observational study.
AB  - OBJECTIVE: Foot temperature has long been advocated as a reliable noninvasive
      measure of cardiac output despite equivocal evidence. The aim of this pilot study
      was to investigate the relationship between noninvasively measured skin
      temperature and the more invasive core-peripheral temperature gradients (CPTGs),
      against cardiac output, systemic vascular resistance, serum lactate, and base
      deficit. RESEARCH METHODOLOGY: The study was of a prospective, observational and
      correlational design. Seventy-six measurements were recorded on 10 adults
      postcardiac surgery. Haemodynamic assessments were made via bolus thermodilution.
      Skin temperature was measured objectively via adhesive probes, and subjectively
      using a three-point scale. SETTING: The study was conducted within a tertiary
      level intensive care unit. RESULTS: Cardiac output was a significant predictor
      for objectively measured skin temperature and CPTG (p=.001 and p=.004,
      respectively). Subjective assessment of skin temperature was significantly
      related to cardiac output, systemic vascular resistance, and serum lactate
      (p<.001, respectively). CONCLUSIONS: These results support the utilisation of
      skin temperature as a noninvasive marker of cardiac output and perfusion. The use
      of CPTG was shown to be unnecessary, given the parallels in results with the less
      invasive skin temperature parameters. A larger study is however required to
      validate these findings.

PMID- 18621530
TI  - Structure-activity relationship study of bone morphogenetic protein (BMP)
      signaling inhibitors.
AB  - A structure-activity relationship study of dorsomorphin, a previously identified
      inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type
      1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be
      accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The
      activity contributions of various nitrogen atoms in the core pyrazolo[1,5
      a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2
      a]pyrimidine and pyrazolo[1,5-a]pyridine derivatives. In addition, increased
      mouse liver microsome stability was achieved by replacing the ether substituent
      on the pendent phenyl ring with piperazine. Finally, an optimized compound 13
      (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics
      (e.g., plasma t(1/2)=1.6h) following intraperitoneal administration in mice.
      These studies provide useful molecular probes for examining the in vivo
      pharmacology of BMP signaling inhibition.

PMID- 18621533
TI  - Wearing the F-Scan mobile in-shoe pressure measurement system alters gait
      characteristics during running.
AB  - This study investigated the influence of wearing an F-Scan mobile in-shoe
      pressure measurement system on running characteristics. Six subjects ran on a
      treadmill at three speeds (3.5 ms(-1), 4.5 ms(-1) and 5.4 ms(-1)) with and
      without wearing the F-Scan system while kinematic data were collected at 240 Hz
      using a motion capture system. Six gait cycles were selected for analysis, with
      touchdown and toe-off visually identified based on foot markers displacement.
      Spatio-temporal gait parameters including stride frequency, stride length, stride
      length relative to height, and stance time were determined. A 2x3 ANOVA with
      repeated measures (alpha=0.05) was performed to identify differences in each gait
      parameter between running with and without the F-Scan system at different speeds.
      Wearing the F-Scan system did not affect the stance time but lead to an increase
      in stride frequency (P<0.05) and a decrease in stride length (P<0.05) and
      relative stride length (P<0.05). As speed increased, stance time decreased while
      stride frequency, stride length and relative stride length increased (all
      P<0.001). These results imply that wearing the F-Scan system alters gait
      characteristics and therefore data obtained may not represent those in a real
      life setting, at least in the case of running. One should take into account the
      potential risk of the movement of interest being altered when interpreting data
      obtained while subjects were wearing the F-Scan system. Future instrumentation
      should minimize the potential influence a measurement device may have on natural
      movement.

PMID- 18621532
TI  - A pig allograft model of antibody-mediated rejection.
AB  - Allograft rejection caused by antibodies in sensitised individuals remains a real
      problem in human allotransplantation. There would be value in a simple model of
      this process to evaluate the mechanisms involved in antibody-mediated damage and
      the development of accommodation, as well as the impact of potential
      interventions. We have thus developed a novel large animal model of this process
      using an allosensitisation system. Two inbred lines of miniature pigs that carry
      different major histocompatibility antigen haplotypes were used. Pigs of one line
      were sensitised by the sequential subcutaneous injection of major
      histocompatibility antigen-mismatched allogeneic peripheral blood mononuclear
      cells derived from the other inbred line. We demonstrated that this generated
      high titres of allospecific antibodies. We then transplanted carotid arteries
      from donors syngeneic to the priming cells into the sensitised animals. After 48
      h these vessels showed a profound mononuclear cell inflammatory infiltrate in
      both intima and media, fibrin deposition, and luminal compromise with thrombus
      and antibody deposition. The mean endothelial surface affected by this process
      was 59.2%. No such pathology was seen in any of the controls. This model is
      technically simple to perform with few post-operative complications. It provides
      proof-of-principle of a model of antibody-mediated rejection which will be of
      potential value in elucidating the mechanisms underlying the process and the
      efficacy of interventions to prevent or treat it.

PMID- 18621534
TI  - Expression of hypoxia inducible factor-1alpha in tumors of patients with
      glioblastoma multiforme and transitional meningioma.
AB  - Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the major transcriptional factor
      involved in the adaptive response to hypoxia. The aim of this study was to assess
      HIF-1alpha in 22 patients with transitional meningioma (TM) and 26 patients with
      glioblastoma multiforme (GBM). HIF-1alpha was assessed using a commercially
      available enzyme-linked immunosorbent assay-based HIF-1 transcription factor
      assay. Levels of HIF-1alpha in TM and GBM were measured using optical density at
      450nm, and median values were found to be 0.35 for TM and 0.37 OD for GBM,
      respectively. There was no statistically significant difference between the two
      types of tumor (p=0.264). These findings indicate that HIF-1alpha is elevated in
      both TM and GBM, suggesting that although hypoxia is one of the most important
      and powerful stimuli for HIF-1alpha elevation and consequently angiogenesis,
      other mechanisms may play roles in HIF-1alpha stimulation in benign brain tumors
      such as TM.

PMID- 18621535
TI  - Alternative splicing resulting in nonsense-mediated mRNA decay: what is the
      meaning of nonsense?
AB  - Alternative splicing (AS) strongly affects gene expression by generating protein
      isoform diversity. However, up to one-third of human AS events create a premature
      termination codon that would cause the resulting mRNA to be degraded by nonsense
      mediated mRNA decay (NMD). The extent to which such events represent functionally
      selected post-transcriptional gene control, as opposed to noise in the splicing
      process, has been a contentious issue. Recent analyses indicate that many
      splicing regulatory proteins are themselves regulated by AS-NMD. Intriguingly,
      many of these AS-NMD events are coincident with ultraconserved genomic elements,
      which indicates their importance to vertebrate biology. Examination of these
      highly conserved events has led to new insights into the functions of AS-NMD and
      the role it can have in physiological circumstances.

PMID- 18621536
TI  - QSAR study of imidazoline antihypertensive drugs.
AB  - The hypotensive effect of imidazoline ligands was attributed to both alpha(2)
      adrenergic receptors and nonadrenergic imidazoline-1 receptors (I(1)-R).
      Selective I(1)-R ligands, devoid of the typical side effects of other centrally
      acting antihypertensive drugs, could be widely used in antihypertensive therapy.
      Thus, there is significant interest in developing new imidazoline analogs with
      higher selectivity and affinity for I(1) receptors. The quantitative structure
      activity relationship (QSAR) study of 12 ligands was carried out using
      multilinear regression method on I(1)-R and alpha(2)-adrenergic receptors binding
      affinities on human platelets. The compounds have been studied using Becke3LYP/3
      21G (d,p) and Becke3LYP/6-31G(d,p) DFT methods. Among 42 descriptors that were
      considered in generating the QSAR model, three descriptors such as partial atomic
      charges of nitrogen in the heterocyclic moiety, distribution coefficient, and
      molar refractivity of the ligands resulted in a statistically significant model
      with R(2)=0.935 and cross-validation parameter q(2)(pre) =0.803. The validation
      of the QSAR models was done by cross-validation and external test set prediction.
      The developed multiple linear regression models for the I(1)-R ligands were aimed
      to link the structures to their reported I(1)-R binding affinity log(1/K(i)). The
      theoretical approach indicates that an increase in distribution coefficient and
      molar refractivity value, together with a decrease in average N-charge in the
      heterocyclic moiety of the ligands, causes better binding affinity for active
      site of the I(1) receptors. The developed QSAR model is intended to predict I(1)
      R binding affinity of related compounds and to define possible physicochemical,
      electrical, and structural requirements for selective I(1)-receptor ligands.

PMID- 18621537
TI  - Application of alpha track registration technique for plutonium estimation in
      bioassay samples.
AB  - Bioassay monitoring is carried out for occupational workers handling plutonium
      (Pu) in nuclear facilities. In India, presently Pu estimation in bioassay samples
      is done by alpha spectrometry. The minimum detectable activity (MDA) of alpha
      spectrometry is 0.5mBq for a counting period of 1 day. To reduce the load of
      sample counting on alpha spectrometry, an alternative method based on alpha track
      registration in solid state nuclear track detectors (SSNTDs) is developed in the
      present paper. For this purpose, few urine samples of normal subjects spiked with
      known amounts of Pu in the range of 0.5-5.5mBq were exposed to CR-39 SSNTDs. The
      total number of alpha tracks seen in the CR-39 films of the sample and the
      standard were used to calculate the amount of Pu in the sample. The results of
      alpha track registration technique were also compared with that obtained by the
      well-established alpha spectrometry and were found to agree well within +/-30%.
      The minimum amount of Pu that can be analyzed by this method is 0.18mBq for an
      exposure period of 45 days.

PMID- 18621538
TI  - Chronic post-traumatic pseudoaneurysm of the innominate artery with an associated
      bovine aortic arch resulting in airway obstruction.

PMID- 18621539
TI  - Risk factors for posterior ventricular rupture after mitral valve replacement:
      results of 2560 patients.
AB  - OBJECTIVE: Posterior ventricular rupture is a rare and fatal complication of
      mitral valve surgery. This study is designed to define the risk factors for left
      ventricular rupture after mitral valve replacement and, especially, to find out
      if posterior leaflet preservation is protective for posterior ventricular
      rupture. METHODS: Between January 1996 and March 2007, 2560 patients underwent
      mitral valve replacement operation in our hospital. Risk factors for posterior
      ventricular rupture were studied with chi(2) and logistic regression analysis.
      RESULTS: The surgery was complicated with posterior ventricular rupture in 23
      (0.8%) of 2560 patients. Nineteen patients (82.6%) were female, four patients
      (17.4%) were male. Mean age of the patients in this group was 60+/-10. Mortality
      rate of the patients with posterior ventricular rupture was 86% (20 patients).
      Twelve patients with posterior ventricular rupture were at the age of 60 and
      older. Age of 60 and above was found as a highly significant risk factor for
      posterior ventricular rupture (OR 4.53, 95% CI 1.98-10.38, p<0.001). Posterior
      leaflet was preserved in 513 patients (20%) and posterior ventricular rupture did
      not occur in these patients. Resection of posterior leaflet was also found as a
      highly significant risk factor (p=0.008) for posterior ventricular rupture.
      Reoperation was performed in 372 patients and posterior ventricular rupture
      occurred in 7 of them. Reoperation was also found as a significant risk factor
      (OR 2.563, 95% CI 1.03-6.34, p=0.042) for posterior ventricular rupture.
      CONCLUSIONS: Extreme annular traction and aggressive decalcification should be
      avoided during mitral valve resection. Posterior leaflet of the mitral valve
      should be preserved, especially in the older age group to prevent posterior
      ventricular rupture.

PMID- 18621540
TI  - Late posterior failure after mitral valve repair in degenerative disease.
AB  - OBJECTIVES: Little is known regarding the mechanisms, the feasibility and the
      long-term results of re-repair in 'posterior failure' of a previous mitral valve
      repair performed for severe degenerative mitral regurgitation. We report our 16
      year experience in redo surgery for late posterior failure of mitral valve repair
      in degenerative disease. METHODS: From 1991 to 2004, 13 consecutive patients (10
      males; median age: 65 years) were reoperated for late posterior failure of mitral
      valve repair. All patients had grade > or =3+ mitral regurgitation. Repair was
      mainly performed using Carpentier's techniques. RESULTS: Repair failure was due
      to posterior leaflet prolapse, leaflet retraction or leaflet dehiscence in eight
      (62%), three (23%) and two (15%) patients, respectively. Repair was performed in
      nine patients (69%). There was no perioperative death. During follow-up (median:
      105 months; range: 40-170 months) one late death occurred in the mitral valve
      replacement group. One (11%) patient underwent mechanical mitral valve
      replacement 125 months after re-repair. Congestive heart failure occurred in one
      patient in each group. At the latest follow-up, all but one patient in the mitral
      valve repair group were in NYHA functional class I or II and all were in sinus
      rhythm. Doppler echocardiographic studies of the re-repaired valves (n=8) showed
      no or trivial, grade 1+ and grade 2+ residual mitral regurgitation in 6 (75%), 1
      and 1 patients, respectively. Mean transmitral gradient was 3 mmHg (2-8 mmHg) and
      left ventricular ejection fraction was 59% (43-77%). CONCLUSION: In case of late
      posterior failure of mitral valve repair for severe degenerative, re-repair is
      feasible in about 70% of the patients with encouraging results at 10 years.

PMID- 18621541
TI  - The emerging role of the intensive care nurse practitioner.

PMID- 18621543
TI  - Fluorescent nanocrystal-encoded microbeads for multiplexed cancer imaging and
      diagnosis.
AB  - Bead-based assays on very large numbers of molecules in proteomics, genomics,
      drug screening and clinical diagnostics require encoding of each of the
      microbeads according to the particular ligand bound to its surface. The benefits
      of using optically encoded microbeads (instead of the solid-state two-dimensional
      arrays) are derived from the freedom of bead to move in three dimensions.
      Polymeric beads optically encoded with organic dyes allow for a limited number of
      unique codes whereas the use of semiconductor nanocrystals as fluorescent tags
      improves the beads multiplexed imaging capabilities, photostability and
      sensitivity of the antigen detection. Additionally, an employment of the recently
      demonstrated Forster resonance energy transfer (FRET) from the microbeads
      nanocrystal codes to the nearby antibody dye label allows for the very specific
      detection of the interaction between the microbead and the antibody. This
      interaction turns the fluorescence signal from dye label off and on thus
      effectively discriminating between the occurrence and the non-occurrence of
      antibody binding. The absence of fluorescent background from non-interacting with
      the beads dye-labelled antibodies additionally increases the sensitivity of
      detection and further facilitates the multiplexing capabilities of nanocrystals
      based detection and diagnostics. This paper reviews the state-of-the-art results
      of development of microbeads optically encoded with the fluorescent nanocrystals
      "quantum dots" and their applications to proteomics for cancer antigens and
      autoantibodies imaging and diagnosis.

PMID- 18621544
TI  - Differential IL-6 and VEGF secretion in adult and neonatal mesenchymal stem
      cells: role of NFkB.
AB  - Stem cells have shown promise for the treatment of end organ ischemia. NFkB has
      been demonstrated to regulate growth factor secretion in human adult bone marrow
      stem cells (aBMSCs). We hypothesized that: (1) NFkB is an important mediator in
      aBMSC and neonatal BMSC (nBMSC) VEGF and IL-6 secretion; and (2) inhibition of
      NFkB will result in a decrease of VEGF and IL-6 in nBMSCs. BMSCs were plated and
      exposed to TNF (50 ng/ml) or LPS (100 ng/ml), with or without NFkB or IKK
      inhibition. VEGF and IL-6 were measured via ELISA in 24-h supernatants.
      Inhibition of NFkB and IKK both demonstrated a decrease in VEGF (p<0.05) in
      aBMSCs but not nBMSCs. The LPS-stimulated nBMSC with IKK inhibition group was the
      only exception which demonstrated a decrease in VEGF secretion. However, both
      NFkB inhibition caused both aBMSCs and nBMSCs to produced less IL-6 after LPS
      stimulation (p<0.05). Only aBMSCs' secretion of IL-6 decreased with NFkB and IKK
      inhibition when stimulated with TNF (p<0.05) differing only when TNF-stimulated
      nBMSCs were inhibited with IKK. VEGF and IL-6 secretion in aBMSCs is dependent on
      the classic NFkB pathway. However, neonatal BMSC VEGF and IL-6 secretion is
      stimulant-specific and utilization of the NFkB pathway is more complex.

PMID- 18621545
TI  - Expression, purification, and characterization of a functionally active
      Mycobacterium tuberculosis UDP-glucose pyrophosphorylase.
AB  - Tuberculosis, which is caused by Mycobacterium tuberculosis, remains to be a
      global health problem. The thick and complex cell envelope has been implicated in
      many aspects of the pathogenicity of M. tuberculosis. M. tuberculosis UDP-glucose
      pyrophosphorylase (UGP, coded by galU, Rv0993) is involved in cell envelope
      precursor synthesis. UGP catalyzes the reversible formation of UDP-glucose and
      inorganic pyrophosphate from UTP and glucose 1-phosphate (Glc-l-P). Bacterial
      UGPs are completely unrelated to their eukaryotic counterparts. This enzyme is
      recognized as a virulence factor in several bacterial species and is conserved
      among mycobacterial species, which makes it a good target for mycobacterial
      pathogenicity research. The recombinant M. tuberculosis UGP (rMtUGP) was purified
      in Escherichia coli and found to be stable and catalytically active. The effects
      of pH, temperature and Mg2+ on enzyme activity were characterized. In addition,
      subcellular localization studies revealed that most of M. tuberculosis UGP
      protein was located in the cell wall. The purification and characterization of M.
      tuberculosis UGP may help to decipher the pathogenicity of M. tuberculosis.

PMID- 18621546
TI  - A Script-Assisted Microscopy (SAM) package to improve data acquisition rates on
      FEI Tecnai electron microscopes equipped with Gatan CCD cameras.
AB  - High throughput methods of data acquisition are advantageous for cryoelectron
      microscopy and single particle reconstruction as high-resolution structure
      determination requires thousands of particle images. We have developed a semi
      automated data collection method that utilizes the scripting languages provided
      by FEI for their Tecnai User Interface (TUI) and by Gatan for their Digital
      Micrograph package. Our Script-Assisted Microscopy (SAM) method allows for the
      selection of multiple locations within a low magnification, search mode,
      micrograph and for subsequent automated imaging of these locations at a higher
      exposure magnification. The SAM approach permits the user to retain control over
      the microscope, while streamlining the most repetitive steps of collecting and
      evaluating micrographs. With SAM, we have found an average of 1000 micrographs
      can be collected per day on any grid type, either irregular homemade grids or
      prefabricated grids with regularly spaced holes. This rate of data collection
      represents a fivefold improvement over our manual collection rates. SAM provides
      an example of an individually tailored approach to data acquisition utilizing the
      scripting interfaces provided by the equipment manufacturers. The SAM method has
      proven valuable for determination of a subnanometer resolution cryoEM structure
      of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a 469kDa protein.

PMID- 18621547
TI  - Effects of electromyostimulation versus voluntary isometric training on elbow
      flexor muscle strength.
AB  - The purpose of this study was to determine whether 7 weeks of standardized (same
      number and duration of repetitions, sets and rest strictly identical)
      electromyostimulation training of the elbow flexor muscles would induce strength
      gains equivalent to those of voluntary isometric training in isometric, eccentric
      and concentric contractions. Twenty-five males were randomly assigned to an
      electromyostimulated group (EMS, n=9), a voluntary isometric group (VOL, n=8), or
      a control group (CON, n=8). Maximal voluntary isometric, eccentric and concentric
      strength, electromyographic (EMG) activity of the biceps and triceps brachii
      muscles, elbow flexor muscle activation (twitch interpolation technique) and
      contractile properties were assessed before and after the training period. The
      main findings were that the isometric torque gains of EMS were greater than those
      of VOL after the training period (P<0.01) and that the eccentric and concentric
      torque gains were equivalent. In both groups, we observed that the mechanical
      twitch (Pt) was increased (P<0.05) and that torque improvements were not mediated
      by neural adaptations. Considering the respective intensities of the training
      programs (i.e., submaximal contractions for EMS versus maximal for VOL), it can
      be concluded that electromyostimulation training would be more efficient than
      voluntary isometric training to improve both isometric and dynamic strength.

PMID- 18621548
TI  - Group independent component analysis of language fMRI from word generation tasks.
AB  - Language fMRI has been used to study brain regions involved in language
      processing and has been applied to pre-surgical language mapping. However, in
      order to provide clinicians with optimal information, the sensitivity and
      specificity of language fMRI needs to be improved. Type II error of failing to
      reach statistical significance when the language activations are genuinely
      present may be particularly relevant to pre-surgical planning, by falsely
      indicating low surgical risk in areas where no activations are shown.
      Furthermore, since the execution of language paradigms involves cognitive
      processes other than language function per se, the conventional general linear
      model (GLM) method may identify non-language-specific activations. In this study,
      we assessed an exploratory approach, independent component analysis (ICA), as a
      potential complementary method to the inferential GLM method in language mapping
      applications. We specifically investigated whether this approach might reduce
      type II error as well as generate more language-specific maps. Fourteen right
      handed healthy subjects were studied with fMRI during two word generation tasks.
      A similarity analysis across tasks was proposed to select components of interest.
      Union analysis was performed on the language-specific components to increase
      sensitivity, and conjunction analysis was performed to identify language areas
      more likely to be essential. Compared with GLM, ICA identified more activated
      voxels in the putative language areas, and signals from other sources were
      isolated into different components. Encouraging results from one brain tumor
      patient are also presented. ICA may be used as a complementary tool to GLM in
      improving pre-surgical language mapping.

PMID- 18621550
TI  - Structure and evolution of the mitochondrial genomes of Haematobia irritans and
      Stomoxys calcitrans: the Muscidae (Diptera: Calyptratae) perspective.
AB  - We present the first two mitochondrial genomes of Muscidae dipterans for the
      species Haematobia irritans (the horn fly) and Stomoxys calcitrans (the stable
      fly). Typical insect mtDNA features are described, such as a high A+T content
      (79.1% and 78.9%, respectively), the preference for A+T-rich codons, and the
      evidence of a non-optimal codon usage. The strong A+T enrichment partially masks
      another nucleotide content bias maintained by A+C mutation pressure in these
      Muscidae mtDNAs. The analysis of this data provides a model of metazoans tRNA
      anticodon evolution, based on the selection hypothesis of anticodon versatility.
      H. irritans mitochondrial genome (16078 bp) is structurally similar to the
      hypothetical ancestral mitochondrial genome of arthropods and its control region
      (A+ T-rich region in insects) organization is consistent with the structure
      described for Brachycera dipterans. On the other hand, the mitochondrial genome
      of S. calcitrans is approximately 2kb longer (18 kb), characterized by the
      presence of approximately 550 bp tandem repeats in the control region, and an
      extra copy of trnI remarkably similar to a duplicated element of blowflies mtDNA.
      Putative sequence elements, involved in the regulation of transcription and
      replication of the mtDNA, were reliably identified in S. calcitrans control
      region despite the 0.8-1.5 kb gap uncovered from this genome. The use of amino
      acid and nucleotide sequences of concatenated mitochondrial protein-coding genes
      (PCGs) in phylogenetic reconstructions of Diptera does not support the monophyly
      of Muscomorpha, as well as the monophyly of Acalyptratae. Within the Calyptratae
      group, the inclusion of Muscidae (Muscoidea) as a sister group of Calliphoridae
      (Oestroidea) implies in a potential conflict concerning the monophyly of the
      superfamily Oestroidea.

PMID- 18621549
TI  - Abundance and location of proteoglycans and hyaluronan within normal and
      myxomatous mitral valves.
AB  - INTRODUCTION: Extracellular matrix changes occur in many heart valve pathologies.
      For example, myxomatous mitral valves are reported to contain excess
      proteoglycans and hyaluronan. However, it is unknown which specific proteoglycans
      are altered in myxomatous valves. Because proteoglycans perform varied functions
      in connective tissues, this study was designed to identify and localize three
      matrix-associated proteoglycans, as well as hyaluronan and the hyaluronan
      receptor for endocytosis, within myxomatous and normal mitral valves. METHODS:
      Human mitral posterior leaflets (control, n=6-9; myxomatous, n=14-21; mean age,
      61 years for all groups) were histochemically stained for proteoglycan core
      proteins, hyaluronan, and the hyaluronan receptor for endocytosis. Stain
      intensity was semiquantitatively graded to determine differences in marker
      abundance between normal and myxomatous valves. The proteoglycans were localized
      to different regions of the leaflet by correspondence to parallel Movat-stained
      sections. RESULTS: The proteoglycans decorin, biglycan, and versican were more
      abundant in myxomatous valves than in normal controls (P<.03). There was a gender
      effect on proteoglycan presence, but no age-related trends were observed.
      Hyaluronan and the hyaluronan receptor for endocytosis were distributed
      throughout all valves. There was no significant difference in hyaluronan between
      groups, but expression of the hyaluronan receptor for endocytosis was reduced in
      myxomatous valves compared to normal controls (P<.002). CONCLUSION: Excess
      decorin, biglycan, and versican may be associated with the remodeling of other
      matrix components in myxomatous mitral valves. Decreased expression of the
      hyaluronan receptor for endocytosis in myxomatous valves suggests that hyaluronan
      metabolism could be altered in myxomatous mitral valve disease. These findings
      contribute towards elucidating the pathogenesis of myxomatous mitral valve
      disease and developing potential new therapies.

PMID- 18621551
TI  - Nuclear and cpDNA sequences combined provide strong inference of higher
      phylogenetic relationships in the phlox family (Polemoniaceae).
AB  - Members of the phlox family (Polemoniaceae) serve as useful models for studying
      various evolutionary and biological processes. Despite its biological importance,
      no family-wide phylogenetic estimate based on multiple DNA regions with complete
      generic sampling is available. Here, we analyze one nuclear and five chloroplast
      DNA sequence regions (nuclear ITS, chloroplast matK, trnL intron plus trnL-trnF
      intergeneric spacer, and the trnS-trnG, trnD-trnT, and psbM-trnD intergenic
      spacers) using parsimony and Bayesian methods, as well as assessments of
      congruence and long branch attraction, to explore phylogenetic relationships
      among 84 ingroup species representing all currently recognized Polemoniaceae
      genera. Relationships inferred from the ITS and concatenated chloroplast regions
      are similar overall. A combined analysis provides strong support for the
      monophyly of Polemoniaceae and subfamilies Acanthogilioideae, Cobaeoideae, and
      Polemonioideae. Relationships among subfamilies, and thus for the precise root of
      Polemoniaceae, remain poorly supported. Within the largest subfamily,
      Polemonioideae, four clades corresponding to tribes Polemonieae, Phlocideae,
      Gilieae, and Loeselieae receive strong support. The monogeneric Polemonieae
      appears sister to Phlocideae. Relationships within Polemonieae, Phlocideae, and
      Gilieae are mostly consistent between analyses and data permutations. Many
      relationships within Loeselieae remain uncertain. Overall, inferred phylogenetic
      relationships support a higher-level classification for Polemoniaceae proposed in
      2000.

PMID- 18621552
TI  - Molecular phylogeny of the brachyuran crab superfamily Majoidea indicates close
      congruence with trees based on larval morphology.
AB  - In this study, we constructed the first molecular phylogeny of the diverse crab
      superfamily Majoidea (Decapoda: Pleocyemata: Brachyura), using three loci (16S,
      COI, and 28S) from 37 majoid species. We used this molecular phylogeny to
      evaluate evidence for phylogenetic hypotheses based on larval and adult
      morphology. Our study supports several relationships predicted from larval
      morphology. These include a monophyletic Oregoniidae family branching close to
      the base of the tree; a close phylogenetic association among the Epialtidae,
      Pisidae, Tychidae, and Mithracidae families; and some support for the monophyly
      of the Inachidae and Majidae families. However, not all majoid families were
      monophyletic in our molecular tree, providing weaker support for phylogenetic
      hypotheses inferred strictly from adult morphology (i.e., monophyly of individual
      families). This suggests the adult morphological characters traditionally used to
      classify majoids into different families may be subject to convergence.
      Furthermore, trees constructed with data from any single locus were more poorly
      resolved than trees constructed from the combined dataset, suggesting that
      utilization of multiple loci are necessary to reconstruct relationships in this
      group.

PMID- 18621553
TI  - Consequences of a Perthes-Bankart lesion in twenty cadaver shoulders.
AB  - This study investigated whether an anteroinferior capsulolabral lesion is
      sufficient to allow the humeral head to dislocate and whether a limited inferior
      approach for creating the lesions influenced the results compared with an all
      arthroscopic approach. Four ligamentous zones of the glenohumeral capsule were
      sequentially detached from the glenoid neck and labrum in 20 cadaver shoulders
      through an inferior approach. Before and after each resection step, inferior
      stability was tested using a sulcus test and anterior stability using a drawer
      test and an apprehension maneuver. Dislocation was only possible when at least 3
      zones were cut. This study confirmed that superior and posterior extension of the
      classic anteroinferior Perthes-Bankart lesion is necessary before the capsular
      restraint in external rotation and abduction is overcome and dislocation occurs.
      Lesions other than the Perthes-Bankart need to be investigated when recurrent
      dislocation is treated, because this anteroinferior injury is most probably not
      the sole factor responsible for the instability.

PMID- 18621554
TI  - Reconstruction of humeral length and centering of the prosthetic head in
      hemiarthroplasty for proximal humeral fractures.
AB  - Anatomic reconstruction of humeral length in hemiarthroplasty for complex
      proximal humeral fractures is difficult because reliable surgical landmarks are
      missing or are destroyed by the fracture. The pectoralis major tendon is a
      reliable landmark to determine prosthetic height intraoperatively. This study
      analyzed the clinical outcome, reconstruction of humeral length, centering of the
      prosthetic head in the glenoid, and tuberosity positioning and healing, using the
      pectoralis major tendon as a reference intraoperatively. The study included 30
      patients. In 21 patients (group 1), humeral length reconstruction was performed
      using the pectoralis major tendon as a reference; in 9 (group 2), this reference
      was not used. Patients underwent a clinical and radiologic evaluation at a mean
      of 22.7 months. Group 1 showed significantly better results in clinical and
      radiologic values, especially in anatomic reconstruction of humeral length, than
      group 2. Clinical outcome depended significantly on greater tuberosity healing
      and centering of the prosthetic head in the glenoid.

PMID- 18621555
TI  - Novel optical imaging technique to determine the 3-D orientation of collagen
      fibers in cartilage: variable-incidence angle polarization-sensitive optical
      coherence tomography.
AB  - OBJECTIVE: To investigate a novel optical method to determine the three
      dimensional (3-D) structure of articular cartilage collagen non-destructively.
      METHODS: Polarization-sensitive optical coherence tomography was used to
      determine the apparent optical birefringence of articular cartilage for a number
      of different illumination directions. A quantitative method based on the theory
      of light propagation in uniaxial crystalline materials was validated on equine
      flexor tendon. Qualitative maps of fiber polar and azimuthal orientation at sites
      on the posterior and anterior segments of the equine third metacarpophalangeal
      (fetlock) joint were produced, and the azimuthal orientations compared with data
      from a split-line experiment. RESULTS: Polar and azimuthal angles of cut flexor
      tendon broadly agreed with the nominal values but suggested that the accuracy was
      limited by our method of determining the apparent birefringence. On intact equine
      fetlock joints we found a non-zero polar tilt that changed in direction at
      various points along the apex, moving from the sagittal ridge outwards. The
      azimuthal orientation changes from being parallel to the sagittal ridge in the
      posterior region to being inclined to the ridge in the anterior region. This
      broadly agrees with split-line data for the anterior region but differs in the
      posterior region, possibly reflecting depth-dependent orientation changes.
      CONCLUSION: General quantitative agreement was found between our method and
      histology in validation experiments. Qualitative results for cartilage suggest a
      complicated 3-D structure that warrants further study. There is potential to
      develop this approach into a tool that can provide depth-resolved information on
      collagen orientation in near real-time, non-destructively and in vivo.

PMID- 18621556
TI  - Systemic administration of a nitric oxide synthase inhibitor impairs fear
      sensitization in the plus-maze.
AB  - The aim of the present study was to evaluate the occurrence of fear sensitization
      in rats previously treated with an inhibitor of the NO syntheses and submitted to
      Trial1/Trial2 plus-maze (PM) procedure. Male Wistar rats received a systemic
      treatment with N(omega)-nitro-L-Arginine-methyl ester (L-NAME; 5, 10 or 50 mg kg(
      1)) and were submitted to PM Trial1. In the following day the animals were re
      exposed to the PM with no drug administration (Trial2). Some standards spatial
      temporal measures, such as the percentage of entries (% Open arm entries) and
      time spent (% Open arm time) in the open arms and risk assessment frequency were
      recorded and used to estimate the animal level of fear sensitization in PM
      Trial2. The results showed that animals receiving L-NAME (50 mg kg(-1)) displayed
      increased % Open arm entries and % Open arm time in Trial2 in relation to the
      group receiving 0.9% saline, which is compatible with impaired fear/anxiety
      acquisition during Trial1/Trial2 PM procedure. In addition, rats treated with L
      NAME (50 mg kg(-1)) exhibited low level of risk assessment in Trial2 in relation
      to the group treated with 0.9% saline, which indicates low level of fear/anxiety
      during PM re-exposure. The number of entries into the enclosed arms was not
      changed by any L-NAME treatment, which suggests no bias of the drug treatments on
      animal locomotor activity. The data suggest that NO synthesis may mediate the
      fear sensitization process in the PM.

PMID- 18621558
TI  - Genome Wide Association Studies: identifying the genes that determine the risk of
      abdominal aortic aneurysm.

PMID- 18621559
TI  - Predominantly post-transcriptional regulation of activation molecules in chronic
      lymphocytic leukemia: the case of transferrin receptors.
AB  - Transcriptional and post-transcriptional control mechanisms have a differential
      impact on cellular physiology depending on activation status. Several lines of
      evidence suggest that chronic lymphocytic leukemia (CLL) malignant B cells
      resemble antigen-experienced and activated B cells. In the present study, we
      investigated the expression of transferrin receptor 1 (TfR1, CD71), one of the
      "classical" markers up-regulated upon B-cell activation, and TfR2, a novel
      receptor for transferrin, in peripheral blood CD19+ B cells from ten healthy
      individuals and 76 patients with CLL so as to gain insight into potential disease
      related differences in underlying regulatory mechanisms. Marked differences in
      the production and expression of these receptors were detected in malignant but
      not in normal B cells. Specifically, TfR1 mRNA and protein levels were
      significantly higher in comparison to TfR2, both in normal and malignant B cells.
      Furthermore, discrepancies between TfR mRNA and protein expression were observed
      in CLL; in contrast, mRNA and protein expression levels were generally concordant
      in normal B cells. Exposure to actinomycin D decreased TfR1 and TfR2 mRNA levels
      in normal CD19+ B cells but had no effect on CLL malignant cells. The protein
      synthesis inhibitor cycloheximide had opposing effects in normal vs. CLL
      malignant B cells: thus, TfR1 and TfR2 mRNA levels were increased in normal B
      cells, whereas they were unaffected or even suppressed in CLL malignant B cells.
      These results allude to differential regulation of TfR1 and TfR2 expression in
      normal B cells vs. CLL. In normal B cells, transcriptional mechanisms exert a
      critical control over TfR1 and TfR2 expression, whereas in CLL post
      transcriptional mechanisms seem to play a complementary and perhaps more
      important role. This type of control appears to be especially suited for
      modulation of genes implicated in proliferation of activated cells, like CLL
      malignant B cells.

PMID- 18621560
TI  - Adenocarcinoma of the disseminated prostate in a cat.
AB  - An adenocarcinoma of the disseminated prostate gland with pulmonary, myocardial
      and renal metastases is described in a 12-year-old, neutered male European cat.
      Histologically, the tumour was localised in the spongy layer of the prostatic
      urethra and showed an epithelial alveolar pattern. Considering the anatomic,
      microscopic and immunohistochemical findings, the tumour was diagnosed as an
      adenocarcinoma of the disseminated prostate gland. To our knowledge this is the
      first report of adenocarcinoma of the disseminated prostate gland in a cat.

PMID- 18621561
TI  - Bartonella: emerging pathogen or emerging awareness?
AB  - The number of known Bartonella species is rapidly growing. Some of them are
      responsible for distinct infectious diseases and show different prevalence and
      antibiotic susceptibility profiles. Not only have some vectors of Bartonella not
      been fully characterized, but also intermediate hosts are actually much more
      numerous and diverse than previously thought. Among these, dogs differ from cats
      because they tend to suffer an overt disease similar to humans, thus providing
      the base for a useful animal indicator and research model. Among the debilitating
      conditions with an unclear impact on the course of these infections, specific
      conditions (e.g., homelessness, alcoholism) have been linked to a much higher
      prevalence and to high risk of unfavorable outcome. Due to the limited arsenal of
      antibiotics effective in vivo on this peculiar intracellular pathogen, the
      risk/benefit balance of antibiotic therapy is sometimes difficult to draw. In
      this evolving picture, the recent discoveries of new species highlights the
      importance of basic molecular biology resources that would bring major public
      health benefits if available in endemic areas, and specifically in many areas of
      Peru and Bolivia.

PMID- 18621562
TI  - The economic impact of aspergillosis: analysis of hospital expenditures across
      patient subgroups.
AB  - OBJECTIVE: To measure the impact of invasive aspergillosis infection on US
      hospital costs and financial performance across different patient populations.
      METHODS: Hospital discharge data for patients with a primary or secondary
      diagnosis of aspergillosis were extracted from the 2003 Nationwide Inpatient
      Sample (NIS) and the fiscal year 2003 (FYO3) Medicare Provider Analysis and
      Review (MedPAR) file. The data on patient demographics, length of stay (LOS),
      hospital charges, estimated costs, and reimbursement levels were reported. After
      controlling for comorbidities, operative procedures, and diagnosis-related group
      (DRG) assignment, the clinical and economic outcomes were compared for patients
      with and without aspergillosis. RESULTS: The NIS contains a total of over 38
      million projected hospital discharges. From these, 10400 aspergillosis cases were
      identified across 171 DRGs, resulting in a US incidence rate of 36 per million
      per year. The mean age of aspergillosis patients was 55.6 years, with 53.4% male
      and 67.9% Caucasian. The median (mean) LOS per aspergillosis patient was 10
      (17.7) days, with a median (mean) total hospital charge (THC) of $44,845
      ($96,731). Among the patient subgroups analyzed, the median (mean) THC per
      patient ranged from $47,252 ($82,946) for HIV to $413,200 ($442,233) for bone
      marrow transplant (BMT). When compared to the non-aspergillosis patient
      population, the data showed a significant increase in LOS, THC, and hospital
      costs. Furthermore, the higher hospital costs associated with aspergillosis
      patients were not matched by similar increases in reimbursements, resulting in a
      greater financial loss for hospitals. The mean reimbursement-to-cost ratio for
      aspergillosis cases across the DRGs analyzed was 0.80. CONCLUSIONS: Aspergillosis
      affects a wide range of patient groups and has a negative economic impact across
      many DRGs. Improved prevention, diagnosis, and patient management strategies can
      help mitigate these effects on hospital financial performance.

PMID- 18621563
TI  - Two cases of bacterial meningitis accompanied by thalidomide therapy in patients
      with multiple myeloma: is thalidomide associated with bacterial meningitis?
AB  - Morbidity and mortality in multiple myeloma is often attributed to life
      threatening infections. A defect in humoral immunity has been proposed for the
      predisposition to bacterial infections. Most of the infections are of bacterial
      origin, and the most serious are septicemia, meningitis, and pneumonia.
      Thalidomide is a drug with pleiotropic effects. The immunomodulatory effects of
      thalidomide are at least partially mediated through its ability to down-regulate
      the pathogenic over-production of tumor necrosis factor-alpha (TNF-alpha). TNF
      alpha is a cytokine that plays a central role in the regulation of the host
      immune and inflammatory response to infection. In the central nervous system, TNF
      alpha is involved in induction of a fever response and triggers the release of
      other cytokines, and may also influence transport of compounds into the brain,
      leading to cerebrospinal fluid leukocytosis, increased protein influx, and
      lactate accumulation. Thalidomide has been shown to down-regulate the production
      of TNF-alpha. On the other hand, knowledge of the effects of thalidomide on
      granulocyte functions is limited. Thalidomide has been shown to attenuate
      neutrophil adhesion and chemotaxis. We present herein two cases of Streptococcus
      pneumoniae bacterial meningitis that developed soon after the initiation of
      thalidomide treatment, and discuss the effect of thalidomide on the immune
      system. Although, it is not clear whether thalidomide caused the development of
      the bacterial infections and meningitis, or what its pathogenetic mechanisms are,
      physicians should be alert for signs and symptoms of meningitis in patients with
      multiple myeloma who are treated with thalidomide, especially those in
      neutropenic states.

PMID- 18621564
TI  - Changes in antioxidant profile among HIV-infected individuals on generic highly
      active antiretroviral therapy in southern India.
AB  - OBJECTIVE: The role of oxidative stress in disease progression has been shown to
      be more complicated in HIV-infected individuals receiving highly active
      antiretroviral therapy (HAART) compared to those who remain treatment-naive. This
      study examined the changes in the antioxidant profile of HIV-infected subjects
      who remained HAART-naive due to a high CD4 cell count and HIV-negative controls,
      over a 12-month follow-up period at YRG CARE, a tertiary HIV referral centre in
      southern India. METHODS: We prospectively studied 35 HIV-infected participants
      (18 on d4T+3TC+EFV (stavudine+lamivudine+efavirenz), eight on AZT+3TC+EFV
      (zidovudine+lamivudine+efavirenz), and nine who were antiretroviral therapy
      naive) and 20 HIV-negative controls. Antioxidant profile (total antioxidant
      status, glutathione reductase, glutathione peroxidase, uric acid, ceruloplasmin,
      zinc, and albumin), CD4 cell count, plasma viral load, dietary intake, and
      history of smoking and alcohol use were determined at baseline and at twelve
      months. RESULTS: At 12 months, participants on HAART showed a significant
      increase in glutathione peroxidase (baseline: 1765 vs. 12 months: 2850U/l;
      p<0.001) and albumin (3.6 vs. 4.4g/dl; p<0.001), and a significant decrease in
      glutathione reductase (52.6 vs. 50.5U/l; p=0.054) and uric acid (5.4 vs.
      4.8mg/dl; p=0.027) compared to baseline. Also HAART-naive participants had a
      significant increase in albumin (baseline: 3.7 vs.12 months: 4.3g/dl; p=0.023)
      and a significant decrease in zinc levels (baseline: 79.0 vs.12 months:
      74.5microg/dl; p=0.052) from baseline to 12 months. HIV-negative subjects had a
      significant increase in glutathione reductase at 12 months from baseline
      (baseline: 37 vs.12 months: 39U/l; p=0.002). No significant difference in total
      antioxidant status, ceruloplasmin, and zinc levels were observed in HAART
      experienced subjects and negative controls over the 12-month follow-up period.
      CONCLUSION: This study documents changes in antioxidants over a period of time in
      HAART-experienced subjects in a southern India setting.

PMID- 18621565
TI  - The role of vascular endothelial growth factor and other endogenous interplayers
      in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a multifaceted disease characterized by
      early subclinical changes at the choroidea-retinal pigment epithelium interface.
      Both the causal and formal pathogenesis of the disease is still puzzling.
      Similarly, the reason for progression into two distinct late forms which are
      "geographic atrophy" and "choroidal neovascularization" remains enigmatic. Late
      changes are usually responsible for the dramatic loss in central function that
      has a devastating effect on quality of life. In industrialized countries the
      disease is a major cause for visual disability among persons over 60 years of
      age. Due to demographic right-shift and increased life expectancy, AMD is not
      only a medical problem but will have a pronounced socio-economic effect.
      Neovascular AMD with the development of choroidal neovascularization in the
      macular area accounts for 80% of the severe loss of visual acuity due to AMD. In
      the last decades, treatment modes were merely based on the destruction or
      surgical removal of the neovascular complex. In the present, however, the
      philosophical approach to treat the disease is changing to a pathology modifying
      manner. Intelligent targeting of the involved relevant factors and pathways
      should stop disease progression, reduce complications and improve vision. The
      first step into this new era has been accomplished with the introduction of
      antiangiogenic agents. The new agents act either directly on vascular endothelial
      growth factor (VEGF) or indirectly on its functional cascade. VEGF makes a
      fundamental contribution to neovascular processes but it also acts in
      physiological pathways. The main purpose of this review is to summarize its
      physiological role especially within the eye, the role in the development of AMD
      and to understand and foresee both the benefits and potential side-effects of the
      anti-VEGF-based therapy.

PMID- 18621566
TI  - Genetic screening for LRRK2 gene G2019S mutation in Parkinson's disease patients
      from Southern Italy.
AB  - Leuchine-rich repeat kinase 2 (LRRK2) gene mutations are a common cause of
      familial and sporadic Parkinson disease (PD). G2019S is the most frequent
      mutation of the LRRK2 gene and has been reported in about 5-6% of familial and 1
      2% of sporadic PD cases. The aim of this study is to investigate the G2019S
      frequency in a series of 58 familial and 70 sporadic PD patients recruited from
      Campania, a region in Southern Italy. We identified one heterozygous G2019S
      mutation in a PD patient who also suffered from obsessive disorder and depression
      and presented hallucinations and delusional jealousy while he was treated with l
      dopa, pramipexole, and amantadine. Brain (18)F-deoxy-glucose PET showed relative
      decrease of glucose metabolism in the caudate nuclei and to a lesser extent in
      cortical parietal/frontal regions. The patient's mother also had PD and molecular
      analysis demonstrated that she carried the same mutation. G2019S mutation
      frequency is rather low in overall patients (0.8%) and in the familial group
      (1.7%), suggesting that it may be an uncommon cause of PD in Southern Italy.

PMID- 18621567
TI  - DARPins: a new generation of protein therapeutics.
AB  - DARPins (designed ankyrin repeat proteins) are a novel class of binding molecules
      with the potential to overcome limitations of monoclonal antibodies, hence
      allowing novel therapeutic approaches. DARPins are small, single domain proteins
      (14 kDa) which can be selected to bind any given target protein with high
      affinity and specificity. These characteristics make them ideal agonistic,
      antagonistic or inhibitory drug candidates. Furthermore, DARPins can be
      engineered to carry various effector functions or combine multiple binding
      specificities, enabling completely new drug formats. Taken together, DARPins are
      a prominent member of the next generation of protein therapeutics with the
      potential to surpass existing antibody drugs.

PMID- 18621568
TI  - Restoration of MRI data for intensity non-uniformities using local high order
      intensity statistics.
AB  - MRI at high magnetic fields (>3.0 T) is complicated by strong inhomogeneous radio
      frequency fields, sometimes termed the "bias field". These lead to non-biological
      intensity non-uniformities across the image. They can complicate further image
      analysis such as registration and tissue segmentation. Existing methods for
      intensity uniformity restoration have been optimized for 1.5 T, but they are less
      effective for 3.0 T MRI, and not at all satisfactory for higher fields. Also,
      many of the existing restoration algorithms require a brain template or use a
      prior atlas, which can restrict their practicalities. In this study an effective
      intensity uniformity restoration algorithm has been developed based on non
      parametric statistics of high order local intensity co-occurrences. These
      statistics are restored with a non-stationary Wiener filter. The algorithm also
      assumes a smooth non-uniformity and is stable. It does not require a prior atlas
      and is robust to variations in anatomy. In geriatric brain imaging it is robust
      to variations such as enlarged ventricles and low contrast to noise ratio. The co
      occurrence statistics improve robustness to whole head images with pronounced non
      uniformities present in high field acquisitions. Its significantly improved
      performance and lower time requirements have been demonstrated by comparing it to
      the very commonly used N3 algorithm on BrainWeb MR simulator images as well as on
      real 4 T human head images.

PMID- 18621569
TI  - Deep inferior epigastric artery perforator free flaps in head and neck
      reconstruction.
AB  - The advantage of free perforator flaps versus free musculocutaneous flaps is the
      reduced morbidity of the donor site with preservation of nerves, muscles and deep
      fascia. In this study, we evaluated the reconstruction results of deep inferior
      epigastric artery perforator (DIEAP) free flaps in the head and neck. A
      retrospective review was performed of 12 patients with head and neck tumor
      ablation defects that were reconstructed with the deep inferior epigastric artery
      perforator (DIEAP) free flaps between January 2004 and December 2006.
      Reconstruction outcomes and complications were measured. Recipient sites were
      subdivided into defects of total or subtotal glossectomy (N=6), three-dimensional
      defects of midface (N=3), through and through defects of the cheek (N=2), and
      anterior skull base resection with an external skin component defect (N=1).The
      overall free flap success rate was 92% (11/12). One DIEAP free flap was lost
      because the draining jugular vein thrombosed. No complications were observed in
      the donor site, including abdominal bulge or hernia. Due to the advantage of
      minimum donor site morbidity, the DIEAP free flap is a new and reliable
      reconstruction choice for head and neck surgical defects.

PMID- 18621570
TI  - GAPD and tubulin are suitable internal controls for qPCR analysis of oral
      squamous cell carcinoma cell lines.
AB  - The selection of housekeeping genes is critical for gene expression studies. To
      address this issue, four candidate housekeeping genes, including several commonly
      used ones, were investigated in oral squamous cell carcinoma cell lines. A simple
      quantitative RT-PCR approach was employed by comparing relative expression of the
      four candidate genes within two cancerous cell lines (HN6 and HN31) and one
      noncancerous cell line (HaCaT) treated or not with EGF and TGF-beta1. Data were
      analyzed using ANOVA followed by the NormFinder software program. On this basis,
      stability of the candidate housekeeping genes was ranked and non statistical
      differences were found using ANOVA test. On the other hand, the NormFinder was
      able to show that GAPD and TUBB presented the less variable results, representing
      appropriated housekeeping genes for the samples and conditions analyzed. In
      conclusion, this study suggests that the GAPD and the TUBB represent adequate
      normalizers for gene profiling studies in OSCC cell lines, covering,
      respectively, high and low expression levels genes.

PMID- 18621571
TI  - Squamous cell carcinoma of the gingivobuccal complex: predictors of locoregional
      failure in stage III-IV cancers.
AB  - The purpose of our study was to analyze the indicators of loco-regional failure
      in a large cohort of patients with gingivobuccal complex tumors treated at a
      single institution. A retrospective review of 2275 patients diagnosed with tumors
      of the gingivobuccal complex was conducted from January 1997 to December 1999;
      642 patients who fulfilled our inclusion criteria were analyzed. A univariate
      analysis, multivariate analysis, and disease-free survival are reported. During a
      median follow up of 2.51 years, there were 228 (35.5%) recurrences with a median
      post-recurrence survival of 2.7 months. The incidence of occult neck metastasis
      was 29%. The 2- and 5-year DFS rates were 63.8% and 53.3%, respectively. On
      multivariate analysis, tumor depth and metastatic lymphadenopathy were found to
      be independent prognostic factors for disease-free survival. Advanced
      gingivobuccal cancers fail loco-regionally. Cervical metastasis and tumor depth
      influence disease-free survival. Elective neck dissection due to a high incidence
      of occult neck disease is recommended.

PMID- 18621573
TI  - Structure alerts for carcinogenicity, and the Salmonella assay system: a novel
      insight through the chemical relational databases technology.
AB  - In the past decades, chemical carcinogenicity has been the object of mechanistic
      studies that have been translated into valuable experimental (e.g., the
      Salmonella assays system) and theoretical (e.g., compilations of structure alerts
      for chemical carcinogenicity) models. These findings remain the basis of the
      science and regulation of mutagens and carcinogens. Recent advances in the
      organization and treatment of large databases consisting of both biological and
      chemical information nowadays allows for a much easier and more refined view of
      data. This paper reviews recent analyses on the predictive performance of various
      lists of structure alerts, including a new compilation of alerts that combines
      previous work in an optimized form for computer implementation. The revised
      compilation is part of the Toxtree 1.50 software (freely available from the
      European Chemicals Bureau website). The use of structural alerts for the chemical
      biological profiling of a large database of Salmonella mutagenicity results is
      also reported. Together with being a repository of the science on the chemical
      biological interactions at the basis of chemical carcinogenicity, the SAs have a
      crucial role in practical applications for risk assessment, for: (a) description
      of sets of chemicals; (b) preliminary hazard characterization; (c) formation of
      categories for e.g., regulatory purposes; (d) generation of subsets of congeneric
      chemicals to be analyzed subsequently with QSAR methods; (e) priority setting. An
      important aspect of SAs as predictive toxicity tools is that they derive directly
      from mechanistic knowledge. The crucial role of mechanistic knowledge in the
      process of applying (Q)SAR considerations to risk assessment should be strongly
      emphasized. Mechanistic knowledge provides a ground for interaction and dialogue
      between model developers, toxicologists and regulators, and permits the
      integration of the (Q)SAR results into a wider regulatory framework, where
      different types of evidence and data concur or complement each other as a basis
      for making decisions and taking actions.

PMID- 18621572
TI  - Parotid-gland-sparing 3D conformal radiotherapy in patients with bilateral
      radiotherapy of the head and neck region--results in clinical practice.
AB  - The aim was to improve the prediction rate of hyposalivation after using a modern
      3D-conformal-radiotherapy-technique (3D-CRT) by sparing of the contralateral
      parotid gland. Between June 2002 and October 2006, 107 patients (90 male, 17
      female, average age: 58 years) with squamous cell carcinoma of the head and neck
      were included in a prospective, non-randomized study. All patients were treated
      using 3D-CRT. Parotid function was assessed by measuring stimulated salivary flow
      before, during and at the end of radiotherapy, as well as 1, 6 and 12 months
      after radiotherapy. Measurements were converted to flow rates and normalized
      relative to that before treatment. Mean doses (D(mean)) were calculated from dose
      volume histograms (DVHs) based on computed tomographies (CTs) for the left and
      right parotid gland separately. Patients were grouped according to the D(mean) of
      the lowest irradiated parotid gland. Group I included all patients who received a
      D(mean)<26Gy (n=23), group II D(mean) 26-40Gy (n=38) and group III D(mean)>40Gy
      (n=46). By the time of 6 months after irradiation, salivary flow rates decreased
      continuously during the therapy. In group I the flow rate decreased to 59%, in
      group II to 40% and in group III to 14%, p<0.05. One year after irradiation a
      recovery effect could be measured in all groups. A sufficient saliva flow rate
      can be proven if one parotid gland is spared with a D(mean) dose <26Gy.
      Approximately, one quarter of the participants showed a significant improvement.

PMID- 18621574
TI  - A development framework for semantically interoperable health information
      systems.
AB  - BACKGROUND: Semantic interoperability is a basic challenge to be met for new
      generations of distributed, communicating and co-operating health information
      systems (HIS) enabling shared care and e-Health. Analysis, design, implementation
      and maintenance of such systems and intrinsic architectures have to follow a
      unified development methodology. METHODS: The Generic Component Model (GCM) is
      used as a framework for modeling any system to evaluate and harmonize state of
      the art architecture development approaches and standards for health information
      systems as well as to derive a coherent architecture development framework for
      sustainable, semantically interoperable HIS and their components. The proposed
      methodology is based on the Rational Unified Process (RUP), taking advantage of
      its flexibility to be configured for integrating other architectural approaches
      such as Service-Oriented Architecture (SOA), Model-Driven Architecture (MDA), ISO
      10746, and HL7 Development Framework (HDF). RESULTS: Existing architectural
      approaches have been analyzed, compared and finally harmonized towards an
      architecture development framework for advanced health information systems.
      CONCLUSION: Starting with the requirements for semantic interoperability derived
      from paradigm changes for health information systems, and supported in formal
      software process engineering methods, an appropriate development framework for
      semantically interoperable HIS has been provided. The usability of the framework
      has been exemplified in a public health scenario.

PMID- 18621575
TI  - Famciclovir treatment options for patients with frequent outbreaks of recurrent
      genital herpes: the RELIEF trial.
AB  - BACKGROUND: Recurrent genital HSV outbreaks are common among those suffering from
      the disease. Antiviral medications taken as suppressive therapy can reduce the
      frequency of these recurrences and reduce viral shedding occurring in between
      recurrences. OBJECTIVES: To investigate the efficacy and safety of oral
      famciclovir as episodic (125 mg twice daily for 5 days) and suppressive (250 mg
      twice daily) treatment of recurrent genital herpes (RGH). STUDY DESIGN: This was
      a randomized, multicenter, 6-month, open-label study. Efficacy variables were
      time to first recurrence of RGH symptoms, and change in total score of the
      Recurrent Genital Herpes Quality of Life (RGHQoL) questionnaire. Subject
      satisfaction questions were summarized. RESULTS: 384 subjects were randomized.
      There was a highly statistically significant difference between treatments in
      time to first recurrence of symptoms in favor of suppressive treatment
      (p<0.0001). There was no significant difference between treatments in total score
      of the RGHQoL or in subject satisfaction with treatment. CONCLUSIONS: This study
      demonstrated that, compared to episodic treatment, suppressive treatment with
      oral famciclovir may extend the time to symptomatic outbreaks in patients with
      frequent recurrences of genital herpes.

PMID- 18621576
TI  - Combination of native and recombinant cytomegalovirus antigens in a new ELISA for
      detection of CMV-specific antibodies.
AB  - BACKGROUND: Serological detection of cytomegalovirus (CMV)-specific antibodies
      varies greatly due to antigen composition and the lack of antigen
      standardization. OBJECTIVES: To develop and evaluate a new ELISA with native
      and/or recombinant cytomegalovirus antigens for the detection of anti-CMV IgG and
      IgM antibodies. RESULTS: The diagnostic performance of three anti-CMV ELISAs
      coated with different CMV antigen preparations, (i) native CMV antigen, (ii) a
      mixture of recombinant CMV peptides pp150, pp28, gB2 and pp52 and (iii) a
      combination of native CMV antigens and recombinant CMV IE1 antigen applied in the
      new Genzyme Virotech CMV ELISA, were compared. All tested sera were derived from
      patients or healthy blood donors and were predefined with the Dade Behring
      Enzygnost CMV ELISA as well as by CMV PCR analysis. Additionally, official well
      characterized serum panels were also tested. The new Genzyme Virotech CMV ELISA
      IgG/IgM test applying a combination of native antigens and recombinant IE1
      antigen was evaluated and the performance was compared to the Dade Behring
      Enzygnost CMV ELISA. The sensitivities were 98.9% (IgG) and 98.2% (IgM), the
      specificities were 98.8% (IgG) and 98.9% (IgM) for the Genzyme Virotech CMV
      ELISA. Furthermore all sera of the BBI mixed titer performance panel as well as
      the BBI seroconversion panel were identified 100% correctly with the new Genzyme
      Virotech ELISA. CONCLUSIONS: These data suggest that the new Genzyme Virotech CMV
      ELISA has higher sensitivity and specificity than ELISAs based on native antigens
      or recombinant peptides only. Specific combinations of native and recombinant
      antigens increase the serological detection of CMV infections and may add to
      further standardization of CMV serology.

PMID- 18621577
TI  - How do feelings cause faints?

PMID- 18621578
TI  - Distinct information processing characteristics in dyslexia and ADHD during a
      covert orienting task: an event-related potential study.
AB  - OBJECTIVE: A visuo-spatial orienting task was used to investigate the individual
      and joint contribution of the presence of dyslexia and attention-deficit
      hyperactivity disorder (ADHD) to information processing. METHODS: Sixteen
      control, 17 dyslexic, 16 ADHD, and 15 comorbid adults performed the task,
      comprising a valid, invalid, and no-cue condition. Performance measures were
      errors and reaction time (RT). A negative potential in response to cues and
      targets (N2), and a positive potential in response to targets (P3) were derived
      from the EEG. A 2x2 design was used with the factors dyslexic/non-dyslexic, and
      ADHD/non-ADHD. RESULTS: Dyslexic participants demonstrated a smaller cue-related
      N2, yet a greater target-related N2 in the valid condition. ADHD participants
      were discriminated by the P3 difference between the invalid and valid conditions.
      Comorbids differed from ADHD mainly in invalid-valid RT, and were similar to
      dyslexics in target N2 processing. CONCLUSIONS: Dyslexics were impaired in early
      information processing, and participants with ADHD differed for later processing
      stages. SIGNIFICANCE: This is the first ERP study of attentional processes in
      dyslexia to incorporate an ADHD and a comorbid group. Its results may contribute
      to differentiation of these clinical groups.

PMID- 18621579
TI  - Reproducibility in nerve conduction studies and F-wave analysis.
AB  - OBJECTIVE: Reproducibility testing of nerve conduction studies and F-wave
      latencies in a group of healthy volunteers. METHODS: A total of 32 healthy
      volunteers underwent sensory and motor nerve conduction studies of the ulnar and
      tibial nerves, including F-waves, elicited by 32 stimuli, repeated in two
      different days by the same examiner. RESULTS: The F-wave latencies showed less
      variability than the other parameters of conduction studies, and, among them, the
      F-wave mean latency of the tibial nerve has been the one with the higher
      reproducibility. CONCLUSIONS: F-wave latencies were the parameters with best
      reproducibility, followed by conduction velocities and amplitudes. SIGNIFICANCE:
      Our data showed that the F-wave mean latency is a parameter with a high
      reliability, considering the reproducibility, for sequential studies.

PMID- 18621580
TI  - A brain-actuated wheelchair: asynchronous and non-invasive Brain-computer
      interfaces for continuous control of robots.
AB  - OBJECTIVE: To assess the feasibility and robustness of an asynchronous and non
      invasive EEG-based Brain-Computer Interface (BCI) for continuous mental control
      of a wheelchair. METHODS: In experiment 1 two subjects were asked to mentally
      drive both a real and a simulated wheelchair from a starting point to a goal
      along a pre-specified path. Here we only report experiments with the simulated
      wheelchair for which we have extensive data in a complex environment that allows
      a sound analysis. Each subject participated in five experimental sessions, each
      consisting of 10 trials. The time elapsed between two consecutive experimental
      sessions was variable (from 1h to 2months) to assess the system robustness over
      time. The pre-specified path was divided into seven stretches to assess the
      system robustness in different contexts. To further assess the performance of the
      brain-actuated wheelchair, subject 1 participated in a second experiment
      consisting of 10 trials where he was asked to drive the simulated wheelchair
      following 10 different complex and random paths never tried before. RESULTS: In
      experiment 1 the two subjects were able to reach 100% (subject 1) and 80%
      (subject 2) of the final goals along the pre-specified trajectory in their best
      sessions. Different performances were obtained over time and path stretches, what
      indicates that performance is time and context dependent. In experiment 2,
      subject 1 was able to reach the final goal in 80% of the trials. CONCLUSIONS: The
      results show that subjects can rapidly master our asynchronous EEG-based BCI to
      control a wheelchair. Also, they can autonomously operate the BCI over long
      periods of time without the need for adaptive algorithms externally tuned by a
      human operator to minimize the impact of EEG non-stationarities. This is possible
      because of two key components: first, the inclusion of a shared control system
      between the BCI system and the intelligent simulated wheelchair; second, the
      selection of stable user-specific EEG features that maximize the separability
      between the mental tasks. SIGNIFICANCE: These results show the feasibility of
      continuously controlling complex robotics devices using an asynchronous and non
      invasive BCI.

PMID- 18621581
TI  - Stochastic resonance in auditory steady-state responses in a
      magnetoencephalogram.
AB  - OBJECTIVE: To see whether stochastic resonance can be triggered in the auditory
      steady-state responses (ASSRs) in a magnetoencephalogram (MEG). METHODS: We
      measured ASSRs to 1kHz sinusoidal tone modulated at 40Hz with various intensities
      of white noise and obtained its power and degree of phase synchrony. RESULTS:
      Group statistics showed a significant enhancement in phase synchrony of ASSR by
      the presence of white noise of appropriate intensity. Tests on individual
      subjects showed that the data of four out of nine subjects exhibited enhancements
      in power or phase synchrony. CONCLUSIONS: The ASSRs exhibit stochastic resonance
      of the so-called I-type (I for information) shown in phase synchrony when
      responding to modulated sinusoidal sound superimposed with weak white noise.
      SIGNIFICANCE: The gamma-band component and other oscillatory components in the
      brain activity have been recently ascribed by some researchers to the result of
      stochastic resonance caused by internal noise in the brain. Therefore the
      presence of stochastic resonance in ASSRs may be evidence to the hypothesis that
      ASSRs are related to the ongoing gamma-band component.

PMID- 18621582
TI  - Association of seizures with cortical spreading depression and peri-infarct
      depolarisations in the acutely injured human brain.
AB  - OBJECTIVE: To test the co-occurrence and interrelation of ictal activity and
      cortical spreading depressions (CSDs) - including the related periinfarct
      depolarisations in acute brain injury caused by trauma, and spontaneous
      subarachnoid and/or intracerebral haemorrhage. METHODS: 63 patients underwent
      craniotomy and electrocorticographic (ECoG) recordings were taken near foci of
      damaged cortical tissue for up to 10 days. RESULTS: 32 of 63 patients exhibited
      CSDs (5-75 episodes) and 11 had ECoGraphic seizure activity (1-81 episodes).
      Occurrence of seizures was significantly associated with CSD, as 10 of 11
      patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test).
      Clinically overt seizures were only observed in one patient. Each patient with
      CSD and seizures displayed one of four different patterns of interaction between
      CSD and seizures. In four patients CSD was immediately preceded by prolonged
      seizure activity. In three patients the two phenomena were separated in time:
      multiple CSDs were replaced by ictal activity. In one patient seizures appeared
      to trigger repeated CSDs at the adjacent electrode. In 2 patients ongoing
      repeated seizures were interrupted each time CSD occurred. CONCLUSIONS: Seizure
      activity occurs in association with CSD in the injured human brain. SIGNIFICANCE:
      ECoG recordings in brain injury patients provide insight into pathophysiological
      mechanisms, which are not accessible by scalp EEG recordings.

PMID- 18621583
TI  - Three families of LTR retrotransposons are present in the genome of the
      choanoflagellate Monosiga brevicollis.
AB  - The choanoflagellates are a ubiquitous group of nanoflagellates and the sister
      group of Metazoa. Examination of the initial draft version of the first
      choanoflagellate genome, that of Monosiga brevicollis, reveals the presence of
      three novel families of long terminal repeat (LTR) retrotransposons and an
      apparent absence of non-LTR retrotransposons and transposons. One of the newly
      discovered LTR families falls in the chromovirus clade of the Ty3/gypsy group
      while the other two families are closely related members of the Ty1/copia group.
      Examination of EST sequences and nucleotide analyses show that all three families
      are transcriptionally active and potentially functional within the genome of M.
      brevicollis.

PMID- 18621586
TI  - The antennal sensilla of the adult of Libellula depressa (Odonata: Libellulidae).
AB  - An ultrastructural investigation (SEM, TEM) on the antennal flagellum of the
      adult of the dragonfly Libellula depressa (Odonata:Libellulidae) revealed
      sensilla located in pits on the lateral-ventral side of the antenna. These
      sensilla are represented by sensilla coeloconica and by deeply sunken sensilla.
      The sensilla coeloconica are innervated by three unbranched dendrites, which
      enter the peg and show a dendrite sheath ending at the base of the peg. The peg
      has no socket and its cuticle is irregular with wide pore-like structures at the
      base of which actual pores are visible. The structure of these coeloconic
      sensilla is in agreement with that reported for single-walled insect
      chemoreceptors. The deeply sunken sensilla are represented by two kinds of
      sensilla styloconica, named type-1 and type-2, located at the bottom of deep
      cavities appearing as simple openings on the antennal surface. These sensilla are
      no-pore sensilla with inflexible socket and unbranched dendrites and,
      notwithstanding their structural differences, share common features typical of
      thermo/hygroreceptors. The presence of chemoreceptors in adult dragonflies sheds
      light on evolutionary trends in insect perception; the previously unknown
      occurrence of thermo/hygroreceptors in dragonflies is very important in view of
      the reported ability of Odonata to thermoregulate heliothermically.

PMID- 18621587
TI  - Caste-specific postembryonic development of primary and secondary olfactory
      centers in the female honeybee brain.
AB  - Eusocial insects are characterized by division of labor among a sterile worker
      caste and a reproductive queen. In the honeybee both female castes are determined
      postembryonically by environmental factors, and queens develop substantially
      faster than workers. Since olfaction plays a crucial role in organizing honeybee
      behavior and social interactions, we compared the development of primary and
      secondary olfactory centers in the brain. Age-synchronized queen and worker pupae
      were raised in incubators at 34.5 degrees C, and their external morphology was
      characterized for all pupal stages. The development of olfactory synaptic
      neuropil was analyzed using anti-synapsin immunocytochemistry, f-actin-phalloidin
      labeling and confocal microscopy. In the antennal lobes of queens olfactory
      glomeruli formed approximately 4 days earlier than in workers. The adult number
      of olfactory glomeruli was in a similar range, but the total glomerular volume
      was slightly smaller in queens. Olfactory and visual subdivisions (lip, collar)
      of the mushroom-body calyx formed early, whereas the basal ring separated late.
      Synaptic microglomeruli in the olfactory lip were established approximately 3-4
      days earlier in queens compared to workers. We propose that developmental
      heterochrony results in fewer synapses in olfactory centers (smaller glomeruli,
      fewer microglomeruli) in queens, which may result in poorer performance on
      olfactory learning tasks compared to workers.

PMID- 18621588
TI  - Aborted sudden death from sustained ventricular fibrillation.
AB  - Ventricular fibrillation usually is sustained and unrelenting in human subjects
      and rarely is self-terminating after 30 seconds' duration. Temporal evolution of
      the arrhythmia in our patient suggested that organization of electrical activity
      varies over time. Interaction of organization with high catecholamine levels and
      hyperkalemia may play a role in self-termination of ventricular fibrillation.
      Understanding the true mechanisms of spontaneous defibrillation may provide newer
      therapeutic options for treatment of this otherwise fatal arrhythmia.

PMID- 18621589
TI  - Effects of cell orientation and electric field frequency on the transmembrane
      potential induced in ellipsoidal cells.
AB  - The transmembrane potential (Deltaphi) induced by external electric fields is
      important both in biotech applications and in new medical therapies. We analyzed
      the effects of AC field frequency and cell orientation for cells of a general
      ellipsoidal shape. Simplified equations were derived for the membrane surface
      points where the maximum Deltaphi is induced. The theoretical results were
      confirmed in experiments with three-axial chicken red blood cells (a:b:c=6.66
      microm:4.17 microm:1.43 microm). Propidium iodide (PI) staining and cell lysis
      were detected after an AC electropermeabilization (EP) pulse. The critical field
      strength for both effects increased when the shorter axis of a cell was parallel
      to the field, as well as at higher field frequency and for shorter pulse
      durations. Nevertheless, data analysis based on our theoretical description
      revealed that the Deltaphi required is lower for the shorter axis, i.e. for
      smaller membrane curvatures. The critical Deltaphi was independent of the field
      frequency for a given axis, i.e. the field strength had to be increased with
      frequency to compensate for the membrane dispersion effect. Comparison of the
      critical field strengths of PI staining in a linear field aligned along semi-axis
      a (142 kV m(-1)) and a field rotating in the a-b plane (115 kV m(-1)) revealed
      the higher EP efficiency of rotating fields.

PMID- 18621590
TI  - Oxidation of chylomicron remnants and vascular dysfunction.
AB  - Recent evidence suggests that chylomicron remnants (CMRs), the lipoproteins which
      carry dietary lipids in the blood, may play a direct role in the initiation of
      atherosclerosis by influencing vascular function. Unlike low-density lipoprotein
      (LDL), CMR do not require prior oxidation to bring about potentially pro
      atherogenic effects on vascular endothelial cell function and macrophage foam
      cell formation. However, CMR carry oxidized lipids from the diet and may also
      become oxidized in the body, thus it is important to establish how the oxidative
      state of the particles may modulate these effects. Pharmacological studies have
      demonstrated that oxidation of CMR significantly enhances their inhibitory
      effects on endothelium-dependent vascular relaxation and their potentiation of
      vasoconstriction in rat and pig arteries. In striking contrast to the effects of
      LDL oxidation, however, the induction of macrophage foam cell formation has been
      found to be inversely related to the oxidative state of CMR. Thus, oxidation of
      CMR has potentially pro-atherogenic effects on endothelial function, but appears
      to protect against foam cell generation. These findings indicate that the
      oxidative state of CMR may cause important changes in the atherogenicity of the
      particles.

PMID- 18621591
TI  - High throughput and sensitive determination of trazodone and its primary
      metabolite, m-chlorophenylpiperazine, in human plasma by liquid chromatography
      tandem mass spectrometry.
AB  - A precise, sensitive and high throughput liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for simultaneous determination of trazodone (TRZ)
      and its primary metabolite, m-chlorophenylpiperazine (mCPP), in human plasma was
      developed and validated. The analytes and the internal standard-nefazodone were
      extracted from 500 microL aliquots of human plasma via liquid-liquid extraction
      in n-hexane. Chromatographic separation was achieved in a run time of 2.5 min on
      a Betabasic cyano column (100 mm x 2.1 mm, 5 microm) under isocratic conditions.
      Detection of analytes and IS was done by tandem mass spectrometry, operating in
      positive ion and multiple reaction monitoring (MRM) acquisition mode. The
      protonated precursor to product ion transitions monitored for TRZ, mCPP and IS
      were m/z 372.2-->176.2, 197.2-->118.1 and 470.5-->274.6 respectively. The method
      was fully validated for its sensitivity, selectivity, accuracy and precision,
      matrix effect, stability study and dilution integrity. A linear dynamic range of
      10.0-3000.0 ng/mL for TRZ and 0.2-60.0 ng/mL for mCPP was evaluated with mean
      correlation coefficient (r) of 0.9986 and 0.9990 respectively. The intra-batch
      and inter-batch precision (%CV) across five validation runs (LLOQ, lower limit of
      quantitation; LQC, low quality control; MQC, middle quality control; HQC, high
      quality control and ULOQ, upper limit of quantitation) was < or =8.4% for both
      the analytes. The method was successfully applied to a bioequivalence study of
      100mg trazodone tablet formulation in 36 healthy Indian male subjects under
      fasting and fed conditions.

PMID- 18621592
TI  - Liver-kidney pathophysiological interrelationships in liver diseases.
AB  - On the basis of several clinical and experimental researches, it is possible
      today to deepen the different mechanisms regarding kidney and liver
      relationships. However, the most studied field remains the renal function during
      liver disease. These alterations can be divided into: 1. Renal functional
      impairment is mainly considered due to hemodynamic derangement with a progressive
      decrease in peripheral vascular resistance (PVR) and an increase in cardiac
      output and rate, characteristic of hyperdynamic circulation, and outer cortex
      renal ischemia. Two principal forms of RFI characterize the hepatorenal syndrome
      (HRS) while in the first stage is based on the simple decrease in renal
      clearances with avid sodium retention. 2. Metabolic renal damage is principally
      due to abnormal serum levels of bile acids, bilirubin and perhaps toxic hepatic
      molecules which induce tubular dysfunction leading to RTA, of which type I, in
      the incomplete form, is the most common, varying between 30% and 50% of cases. It
      is mainly studied during cholestatic disease. 3. Organic renal impairment is
      principally based on immunological response to viral antigens and abnormal
      hepatic products which lead to the presence of immunocomplexes and cryoglobulins
      on the blood which tend to be deposited in the subendothelial and subepithelial
      glomerular areas, inducing complement activation, mesangial cell proliferation
      and monocyte-macrophage cell infiltration.

PMID- 18621593
TI  - The effect of shape on the adhesion of fibrillar surfaces.
AB  - Experimental data have demonstrated that mushroom-shaped fibrils adhere much
      better to smooth substrates than punch-shaped fibrils. We present a model that
      suggests that detachment processes for such fibrils are controlled by defects in
      the contact area that are confined to its outer edge. Stress analysis of the
      adhered fibril, carried out for both punch and mushroom shapes with and without
      friction, suggests that defects near the edge of the adhesion area are much more
      damaging to the pull-off strength in the case of the punch than for the mushroom.
      The simulations show that the punch has a higher driving force for extension of
      small edge defects compared with the mushroom adhesion. The ratio of the pull-off
      force for the mushroom to that of the punch can be predicted from these
      simulations to be much greater than 20 in the friction-free case, similar to the
      experimental value. In the case of sticking friction, a ratio of 14 can be
      deduced. Our analysis also offers a possible explanation for the evolution of
      asymmetric mushroom shapes (spatulae) in the adhesion organ of geckos.

PMID- 18621594
TI  - The submersion technique for vascular injection of perforator flaps.

PMID- 18621595
TI  - Preparing for upper and lower limb surgery in seconds: a technique with
      implications for theatre efficiency and manual handling.

PMID- 18621596
TI  - Functional outcome after facial allograft transplantation in rats.
AB  - BACKGROUND: Full face, hemiface and facial subunit transplants have been reported
      before. However, the functional recovery of the face transplant largely remains
      unknown. The mystacial pad (also known as the vibrissal or whiskers region) is
      the main sensorimotor unit in rats' faces. We included the mystacial region in
      the hemifacial flap of the rat, and our aim was to study its functional recovery
      after transplant. METHODS: Hemifacial flaps were transplanted from Brown-Norway
      RT(n) to Wistar-Lewis RT(l) rats, under tapered doses of tacrolimus
      immunosuppression monotherapy (8 mg/Kg/day to 2mg/Kg/day after 4 weeks). Group I
      (n=12) was the anatomic study group, in which the harvesting technique of the
      flap was trial run and angiographies of the flap were obtained. In group II
      (n=12), non-vascularized hemifacial allografts were transplanted. Group III
      (n=24) was the vascularized hemiface allotransplant group. This was divided into
      two subgroups relating to nerve repairs. In subgroup III(a) (n=12) no nerve
      repairs were performed, while in subgroup III(b) (n=12) the zygomaticoorbital,
      bucolabial and upper marginal mandibular branches of the facial nerve, and the
      infraorbital branch of the trigeminal nerve were repaired. Clinical,
      neurophysiological and histological studies were performed to evaluate the
      recovery of the mystacial region after six weeks. RESULTS: In group I the
      hemifacial flap harvesting technique to include the mystacial region was
      established, and angiographies confirmed a rich axial vascular network in the
      flaps. All grafts in group II necrosed. In group III, each procedure required an
      average of 7h (range 5-11). Of this group, 75% of the rats survived for 8 weeks.
      In subgroup III(a) no signs of recovery were noted, whilst in subgroup III(b)
      clinical, neurophysiological and histological recovery were found in face
      transplant recipients after 6 weeks. CONCLUSIONS: The hemifacial flap including
      the mystacial region could be transplanted successfully in the rat model. Face
      allotransplants in which nerves were repaired showed clinical, neurophysiological
      and histological signs of recovery.

PMID- 18621597
TI  - A very rare complication: keloid formation after circumcision, and its treatment.

PMID- 18621598
TI  - [New trends in lipidology: the increasing role of HDL-cholesterol].
AB  - Previous epidemiological studies have demonstrated the low level of high-density
      lipoprotein (HDL) cholesterol as an independent risk factor for cardiovascular
      diseases, the increase of which is one of the cornerstones of preventive
      cardiovascular care. In addition to its major role in reverse cholesterol
      transport, HDL-C has other biological activities that may contribute to its
      protective effects against atherosclerosis. These include antioxidant, anti
      inflammatory, antithrombotic/profibrinolytic and vasoprotective effects. Current
      guidelines recommend aggressive lifestyle modifications, niacin, fibrate, statin
      or a combination of these to increase HDL-cholesterol levels. In addition,
      several novel HDL-based therapeutic strategies have been or are currently being
      tested. These include newer formulations of nicotinic acid/receptor agonists,
      CETP inhibitors, cannabinoid-1 receptor antagonists, PPAR agonists, liver X
      receptor/farnesoid X receptor agonists, and apoA-I and/or phospholipid-derived
      therapies. In this article previous clinical trials, epidemiological
      observations, basic science studies and the most important trials of novel agents
      are reviewed.

PMID- 18621599
TI  - [High-dose chemotherapy followed by autologous CD34+ stem cell transplantation in
      the treatment of severe refractory multisystem autoimmune diseases of adults-
      first experiences in Hungary].
AB  - High dose chemotherapy followed by autologous stem cell support is a promising
      therapeutical approach in the treatment of severe refractory multisystem
      autoimmune diseases. The aim of this study was to perform the authors' first
      experiences in this field. RESULTS: Between August 2006 and November 2007
      autologous stem cell transplantation was performed for seven patients: two of
      them had systemic lupus erythematosus, four of them had rheumatoid arthritis and
      one of them had systemic sclerosis. Cyclophosphamide plus colony stimulating
      factor were administered to mobilize stem cells. The conditioning protocol
      included high dose cyclophosphamide (200 mg/kg) and anti-thymocyte globulin (9
      mg/kg). The re-infused stem cells were successfully engrafted by all patients.
      One of the lupus patients died on the 46th day due to a lethal cytomegalovirus
      infection, but the rest of them had no severe complications. Complete remission
      of their diseases and significant improvement in their quality of life were
      observed during a mean follow-up period of 10 months. CONCLUSIONS: Autologous
      stem cell therapy can be effectively administered in special cases of severe
      autoimmune disorders.

PMID- 18621600
TI  - [Inclusion body myositis pathomechanism and therapy].
AB  - Inclusion body myositis is an acquired inflammatory muscle disease belonging to
      the family of idiopathic inflammatory myopathy with vacuole formation.
      Approximately 15-28% of idiopathic inflammatory myopathy patients suffer from
      inclusion body myositis. Early diagnosis is very important due to the slowly
      progressive disease course and consecutive muscle atrophy. Inclusion body
      myositis is the most common chronic progressive muscle disease over the age of 50
      years. Both degenerative processes including beta-amyloid accumulation and
      inflammatory processes, such as CD8 positive T-lymphocytes mediated cellular
      cytotoxicity take part in the pathomechanism of the inclusion body myositis.
      These findings are well demonstrated by the parallel presence of vacuolized
      muscle fibers rarely invaded by T cells and intact muscle fibers invaded by
      inflammatory T-cells in biopsy specimens. MHC-I/CD8 complex was introduced into
      the newly revised diagnostic criteria as a specific immune marker which helps to
      differentiate inclusion body myositis from aspecific inflammation present in
      other muscle dystrophies. Clinically both proximal and distal muscle weakness,
      respiratory muscle weakness and dysphagia are present. Interstitial lung disease
      is infrequent. Inclusion body myositis responds poorly to antiinflammatory
      treatment due to the predominant degenerative processes and it often results in
      only biochemical response instead of clinical. Diagnosis and differential
      diagnosis of inclusion body myositis are a very special challenge for the
      physician due to the diagnostic procedures which need immunohistochemical
      background. New therapeutic targets, monoclonal antibodies against the
      costimulatory molecules, anticytokine therapy may provide further improvement in
      the quality of life of inclusion body myositis patients.

PMID- 18621601
TI  - [Genes of longevity].
AB  - Aging, as most of the processes in the organism's life, is under genetic control.
      A handful of genes have become known in the recent decade that are involved in
      this process. Understanding how they work may reveal the keys to longer life
      while banishing diseases of old age. The aim of this paper is to present a review
      of the research to extend the human lifespan.

PMID- 18621602
TI  - [Bela Johan's subjective memories of Antal Genersich and of contemporary
      pathology].

PMID- 18621603
TI  - [Memorial plate to Jozsef Hofner, surgeon of Gyor].

PMID- 18621604
TI  - [In memoriam Pal Braun (1909-1998)].

PMID- 18621607
TI  - Pill-popping and therapeutic outcome.

PMID- 18621608
TI  - Low-dose estrogen therapy to reverse acquired antihormonal resistance in the
      treatment of breast cancer.
AB  - Estrogen is a potent stimulus for growth in its target organs: the uterus,
      vagina, and some estrogen receptor-positive breast cancers. However, estrogen is
      also able to control menopausal symptoms and maintain bone density in
      postmenopausal women. Until recently, there was also believed to be a link
      between estrogen and the prevention of cardiovascular disease. For these reasons,
      hormone replacement therapy (HRT) with an orally active estrogen and progesterone
      has been used routinely for more than 50 years to maintain physiologic
      homeostasis after menopause. Not surprisingly, HRT increases the risk of
      developing breast cancer. The link between estrogen and breast cancer growth
      served as the incentive to develop long-term tamoxifen therapy and, subsequently,
      the aromatase inhibitors (AIs) as successful "anti-estrogenic" treatments.
      Unfortunately, the consequence of exhaustive therapy is drug resistance.
      Laboratory studies have defined the evolution of tumor drug resistance to
      tamoxifen, raloxifene (used for breast and osteoporosis chemoprevention), and the
      AIs. Remarkably, the long-term exposure of breast cancers to antihormonal therapy
      also exposes a vulnerability that is being exploited in the clinic. Years of
      antihormonal therapy alters the cellular response mechanism to estrogen.
      Normally, estrogen is classified as a survival signal in breast cancer, but in
      sensitive antihormone-resistant cells, estrogen induces apoptosis. When resistant
      cells are killed, antihormonal therapy is once again effective. This new targeted
      approach to the treatment of metastatic breast cancer could open the door to
      novel approaches to treatment with drug combinations.

PMID- 18621609
TI  - Defining the role for autologous breast reconstruction after mastectomy: social
      and oncologic implications.
AB  - Breast reconstruction plays a significant role in the management of breast
      cancer. The removal of a breast has implications for the psychologic, social, and
      sexual well-being of the patient, establishing the need for discussion of
      postmastectomy breast reconstruction with suitable patients. However, operative
      morbidity and the potential for diminished oncologic safety are ongoing issues of
      contention. A Medline literature review was performed to evaluate the interplay
      between the psychosocial need for breast reconstruction in patients after
      mastectomy and the issues surrounding its oncologic safety. Immediate breast
      reconstruction does not impair the oncologic safety of breast cancer management,
      with no increase in local recurrence rates, and no delays in the initiation of
      adjuvant chemotherapy or radiation therapy (RT). Immediate breast reconstruction
      in the setting of chemotherapy is not associated with greater complication rates;
      however, there is some evidence for increased complications in the setting of
      adjuvant RT. Breast reconstruction has a positive effect on the psychosocial
      outcomes of mastectomy and is oncologically safe in the immediate and delayed
      settings. Ultimately, the decision-making process of whether to reconstruct, how
      to reconstruct, and when to reconstruct requires a multidisciplinary approach,
      with the patient, plastic surgeon, oncologic surgeon, medical oncologist, and
      radiation oncologist all contributing.

PMID- 18621610
TI  - Method of primary tumor detection as a risk factor for local and distant
      recurrence after breast-conservation treatment for early-stage breast cancer.
AB  - BACKGROUND: Recent studies have shown that breast cancer detected by screening
      has a more favorable prognosis than interval breast cancer. To further understand
      the biologic significance of this finding, we investigated the association of
      disease recurrence, local and distant, with the method of detection of the
      primary breast cancer in a cohort of 1686 women treated with breast conservation.
      PATIENTS AND METHODS: The charts of 1686 women with primarily stage I or II
      invasive breast cancer treated by breast conservation between 1977 and 2002 were
      reviewed. The median length of follow-up was 6 years. Univariate and multivariate
      analyses using binary logistic regression were performed for 2 subgroups: (1)
      those with local recurrence versus those without; and (2) those with distant
      metastasis versus those without distant metastasis. RESULTS: Our data confirmed
      several of the well-known risk factors for local and distant recurrence. In
      addition, we found that individuals with breast cancer detected on physical
      examination alone have a significantly higher risk for local recurrence compared
      with patients with cancer detected on mammogram alone, independent of tumor size
      (odds ratio [OR], 2.369; 95% CI, 1.235-4.547; P = .01). We also found a similar
      correlation for risk of distant metastasis in these 2 groups of women (OR, 2.201;
      95% CI, 1.211-3.998; P = .01). CONCLUSION: Breast cancers that are palpable might
      represent an aggressive biologic subtype with an increased risk of local and
      distant recurrence. Risk stratification might need to include this clinical
      feature in addition to conventional prognostic factors.

PMID- 18621611
TI  - A Phase II study of capecitabine and vinorelbine in patients with metastatic
      breast cancer pretreated with anthracyclines and taxanes.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and safety of
      capecitabine in combination with vinorelbine in patients with metastatic breast
      cancer (MBC) pretreated with anthracyclines and taxanes. PATIENTS AND METHODS: In
      this prospective, multicenter, open-label phase II trial, patients received
      capecitabine (2000 mg/m2 daily, taken in 2 oral doses) on days 1-14 and
      vinorelbine (25 mg/m2 intravenous infusion) on days 1 and 8. Cycles were repeated
      every 3 weeks up to a maximum of 6 cycles, unless disease progression or
      unacceptable toxicity occurred or patient consent was withdrawn. RESULTS: Thirty
      one patients were included and received 152 cycles of chemotherapy, with a median
      of 3 cycles per patient. All patients were evaluated for efficacy and toxicity in
      an intent-to-treat analysis. The overall response rate was 49% (95% CI, 30%-67%),
      including 4 complete (13%) and 11 partial (36%) responses. With a median follow
      up time of 9 months, the median time to disease progression was 7.6 months (95%
      CI, 5.7-9.8 months), and the median survival time was 27.2 months. The most
      frequent severe hematologic toxicities were neutropenia (48% of patients) and
      leukopenia (10% of patients). Vomiting (16% of patients) was the most common
      nonhematologic toxicity, while asthenia, bone pain, dyspnea, plantar-palmar
      erythrodysesthesia, nausea, and transaminase elevation were observed in 6%-10% of
      patients. There was 1 death from septic shock. CONCLUSION: Capecitabine in
      combination with vinorelbine is an effective and safe schedule for patients with
      MBC pretreated with anthracycline- and taxane-containing regimens.

PMID- 18621612
TI  - Insight into barriers against optimal adherence to oral hormonal therapy in women
      with breast cancer.
AB  - BACKGROUND: Suboptimal adherence to prescribed oral anticancer agents has been
      demonstrated in several studies. Understanding the barriers to treatment
      compliance is becoming increasingly important because of the growing number of
      oral agents available to treat women with breast cancer. PATIENTS AND METHODS: To
      identify barriers that affect patient adherence to oral hormonal medications, a
      self-reported, 30-question Internet survey was posted on the Y-ME National Breast
      Cancer Organization Web site, www.y-me.org, from June 30, 2005, through October
      31, 2005. Of the 542 respondents who began the survey, 328 completed it. RESULTS:
      Of those who answered the question related to whether healthcare professionals
      encouraged adherence, only 44.2% reported receiving instruction on the importance
      of taking oral medication as directed at every office visit. For 33%, the topic
      was reportedly discussed only once, and this occurred before treatment. Although
      83.6% of patients indicated that they were taking their oral therapy as directed,
      only 57.4% rated their ability to adhere to therapy as excellent (not missing a
      single dose in the past month). The most frequently cited factors for increasing
      compliance to oral medications were knowing adherence could improve clinical
      outcomes (88.7%) and better management of treatment-related side effects (60.2%).
      CONCLUSION: The results of this survey suggest that treatment adherence could be
      improved if healthcare professionals discuss and emphasize (1) the importance of
      taking oral medications as directed and (2) the effect of adherence on clinical
      outcomes. Additional research is needed to evaluate the optimal methods for
      improving compliance with oral therapy.

PMID- 18621613
TI  - A Phase II trial of split, low-dose docetaxel and low-dose capecitabine: a
      tolerable and efficacious regimen in the first-line treatment of patients with
      HER2/neu-negative metastatic breast cancer.
AB  - BACKGROUND: Successful therapeutic regimens in metastatic breast cancer (MBC)
      must balance efficacy and tolerability. Docetaxel/capecitabine is an active and
      commonly used doublet in this setting. Docetaxel upregulates thymidine
      phosphorylase and thus potentiates the antitumor effects of capecitabine. A
      schedule with split, low-dose docetaxel in combination with low-dose capecitabine
      could improve the therapeutic index of this regimen without compromising its
      clinical activity. PATIENTS AND METHODS: Patients with previously untreated
      HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m2 on
      days 1 and 8 in combination with capecitabine 750 mg/m2 twice daily on days 1-14
      of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years
      (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of
      metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17);
      nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients
      had bone-only disease. All subjects had a performance status of 0/1. A total of
      329 cycles were administered (median, 6; range, 1-50). RESULTS: Of 37 patients
      who received study treatment, 32 had evaluable disease, 1 had a complete
      response, and 15 had a partial response (overall response rate was 50% in
      evaluable patients and 43% in the intent-to-treat analysis). Six patients had
      stable disease. The overall clinical benefit rate was 69% for patients with
      evaluable disease and 60% overall. Fifteen patients had disease that progressed
      or had been withdrawn from study at the time of first evaluation. With a median
      follow-up of 25 months, median time to treatment failure was 4.25 months (95% CI,
      1.5-7 months), and median overall survival has not yet been reached. Toxicity was
      moderate: 15 patients (41%) had grade 3/4 adverse events. CONCLUSION: Split, low
      dose docetaxel and low-dose capecitabine is an active combination in the first
      line treatment of patients with MBC. Toxicity with this schedule was manageable,
      making it an attractive regimen for further study in combination with targeted
      agents.

PMID- 18621614
TI  - Plasminogen activator inhibitor type 1 is the most significant of the usual
      tissue prognostic factors in node-negative breast ductal adenocarcinoma
      independent of urokinase-type plasminogen activator.
AB  - PURPOSE: The aim of the present investigation was to evaluate the prognostic
      significance of urokinase-type plasminogen activator (uPA) and plasminogen
      activator inhibitor-1 (PAI-1) tissue contents in primary breast adenocarcinoma.
      PATIENTS AND METHODS: Patients from 3 medical centers were included between 1994
      and 2001. Biologic factors in tumor extracts were all assayed in the same
      laboratory. PAI-1 and uPA were treated as continuous or dichotomized variables.
      Metastasis-free survival analyses were performed using the Cox model and the
      classification algorithm and regression tree (CART) in the whole population and
      in the subsets of node-negative (pN0) or positive (pN+) cases. Kaplan curves of
      metastasis-free survival were designed for different groups in relation to
      uPA/PAI-1 combinations. Urokinase-type plasminogen activator tumor level appears
      related to the anatomic degree of extension; conversely, PAI-1 tumor content is
      independent of tumor size and nodal extension. RESULTS: In univariate analysis,
      adjusted on usual prognostic factors, the metastasis risk increased with PAI-1
      level in all patients (HR [hazard ratio], 3.1; P < .001), in pN0 (HR, 4.3; P <
      .001), and pN+ patients (HR, 2.3; P = .019). It increased also with uPA in all
      patients (HR, 2.6; P = 0.006). In multivariate analysis, when both variables were
      included, PAI-1 remained significant in all patients (HR, 2.4; P = .002) and pN0
      patients (HR, 3.2; P = .003) but not uPA. CART analyses confirmed that the best
      partitioning factor was PAI-1. CONCLUSION: There was no evidence for any
      additional impact of uPA. PAI-1 is an independent prognostic factor in particular
      in pN0 breast ductal carcinoma.

PMID- 18621615
TI  - Phase II trial of gemcitabine/carboplatin (plus trastuzumab in HER2-positive
      disease) in patients with metastatic breast cancer.
AB  - BACKGROUND: Gemcitabine and carboplatin have significant preclinical synergy, and
      both provide synergistic antitumor activity in metastatic breast cancer (MBC)
      when used in combination with trastuzumab. The gemcitabine/ cisplatin combination
      is highly active in MBC with response rates (RRs) of approximately 50% in
      anthracycline- and taxane-pretreated patients and up to 80% in untreated
      subjects. This phase II trial studied the efficacy and safety of
      gemcitabine/carboplatin with or without trastuzumab in patients with MBC.
      PATIENTS AND METHODS: Patients were stratified into 3 groups: group 1, HER2
      positive; group 2, HER2-negative and taxane- naive/remote (no taxanes within past
      2 years); and group 3, HER2-negative and previous taxane therapy. Included were
      women aged > or = 18 years, Eastern Cooperative Oncology Group performance status
      of 0-2, with Response Evaluation Criteria in Solid Tumors-defined measurable MBC;
      HER2-negative or HER2 (3+) by immunohistochemistry or fluorescence in situ
      hybridization positive. All cycles were repeated every 14 days. On day 1,
      gemcitabine 1500 mg/m2 over 30 minutes was administered followed by carboplatin
      area under the curve of 2.5. Group 1 also received trastuzumab 8 mg/kg on day 1
      of each cycle followed by 4 mg/kg for every 2 weeks thereafter. RESULTS: One
      hundred fifty patients were registered (50, 51, and 49 in groups 1, 2, and 3,
      respectively). The overall RRs were 64%, 27%, and 32%, respectively, with median
      time to progression of 7.2, 5.5, and 4.4 months, respectively. Overall, grade 3/4
      toxicities included neutropenia (45%), leukopenia (17%), and thrombocytopenia
      (7%). Alopecia was infrequent: grade 1 (34%) and grade 2 (3%), and there was no
      significant cardiac toxicity. CONCLUSION: Gemcitabine/carboplatin/trastuzumab is
      highly active in patients with HER2-positive MBC. Gemcitabine/carboplatin is
      active in patients with HER2-negative MBC independent of previous taxane therapy.
      Gemcitabine/carboplatin with or without trastuzumab administered every 2 weeks is
      associated with a low frequency of serious toxicity.

PMID- 18621616
TI  - Primary mucosa-associated lymphoid tissue lymphoma of the breast.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal indolent
      lymphoma with histopatholigic features similar to those of marginal zone B-cell
      lymphomas. Primary breast MALT lymphomas were first described by Lamovec and
      Jancar as a low-grade B-cell lymphoma in 1987. Herein, a case is presented of a
      patient with primary MALT lymphoma of the breast. Issues in diagnosis and breast
      conservation treatment, as it pertains to primary MALT lymphoma of the breast,
      will be discussed.

PMID- 18621617
TI  - Primary carcinoma of ectopic breast tissue.
AB  - We describe a case of a 37-year-old woman with a left axillary mass. Often, the
      initial differential diagnosis of an axillary mass is not easy to make. We
      performed fine-needle aspiration of the axillary mass that revealed the presence
      of numerous epithelial neoplastic cells. A bilateral digital mammography, chest
      and abdomen computed tomography scan, and a magnetic resonance imaging scan (MRI)
      of the axillary region were performed. In our case, the MRI was able to exclude
      the presence of neoplastic tissue in the breast; moreover, it confirmed the
      presence of metastatic lymph nodes and recognized a second type of nodular lesion
      in the axilla, showing on the MRI a radiologic pattern similar to breast tissue.

PMID- 18621618
TI  - Preoperative chemotherapy plus lapatinib or trastuzumab or both in HER2-positive
      operable breast cancer (CHERLOB Trial).

PMID- 18621621
TI  - Gender issues and the molecular epidemiology of lung cancer risk.

PMID- 18621622
TI  - Monoclonal antibodies versus tyrosine kinase inhibitors concurrent with
      chemotherapy in non-small-cell lung cancer: exploring divergent results.

PMID- 18621624
TI  - Molecular epidemiology to better predict lung cancer risk.
AB  - Although it is clear that smoking causes lung cancer, it is not known why some
      smokers develop the disease while others do not. Little is also known regarding
      risk factors for lung cancer among never-smokers, particularly women, or why
      women with lung cancer are more likely to have a family history of cancer, to be
      diagnosed at a young age, or to have adenocarcinoma. The application of molecular
      epidemiology to the study of lung cancer risk might facilitate elucidation of
      these questions. In this review, the molecular epidemiology of lung cancer is
      discussed, with an emphasis on studies of genetic variability in metabolic
      pathways as a means for determining susceptibility. Work that has assessed
      intermediate markers of risk, such as DNA adducts, is also presented, as are
      studies of tumor tissue alterations, such as mutations and DNA methylation, in
      relation to risk of lung cancer. Finally, approaches to evaluating factors that
      might explain the differing epidemiology of lung cancer between men and women are
      also presented. It is likely that, by incorporating biomarkers of susceptibility,
      exposure, and effect, molecular epidemiologic approaches might better define
      factors that explain some of the variability in lung cancer risk.

PMID- 18621625
TI  - A randomized phase II trial of oral topotecan versus docetaxel in the second-line
      treatment of non-small-cell lung cancer.
AB  - BACKGROUND: This randomized phase II trial evaluated the efficacy and toxicity of
      oral topotecan compared with intravenous docetaxel in the second-line treatment
      of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eighty
      patients were randomized to receive topotecan (2 mg per day or 2.5 mg per day
      fixed dose for 5 of 7 days for 2 weeks) or docetaxel (75 mg/m2) every 21 days.
      Thirty-nine patients received 138 cycles of topotecan. RESULTS: The overall
      response rate (RR; ORR) was 8%, median time to progression (TTP) was 1.6 months,
      median survival was 8.4 months, and the 1- and 2-year survival rates were 36% and
      13%, respectively, for patients receiving topotecan. Forty-one patients were
      randomized, but only 38 patients were actually treated with 136 cycles of
      docetaxel. The ORR was 8% (7% intent to treat RR), median TTP was 1.4 months,
      median survival was 7.6 months, and the 1- and 2-year survival rates were 29% and
      13%, respectively, for patients receiving docetaxel. CONCLUSION: Oral topotecan
      appears to be active and well tolerated when administered as a fixed dose daily
      for 5 of every 7 days for 2 weeks every 21 days and might provide another
      treatment alternative for patients with advanced-stage NSCLC.

PMID- 18621626
TI  - Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in
      patients with non-small-cell lung cancer.
AB  - PURPOSE: The aim of this study was to evaluate the safety and tolerability of
      escalating doses of flavopiridol/ paclitaxel/carboplatin in patients with
      advanced-stage non-small-cell lung cancer (NSCLC) as well as the pharmacokinetics
      and activity of flavopiridol when used in combination with
      paclitaxel/carboplatin. PATIENTS AND METHODS: Eligible patients aged 18-75 years
      with previously untreated stage IIIB/IV NSCLC received paclitaxel 175 mg/m2 over
      3 hours followed by carboplatin area under the curve (AUC) 5 over 1 hour and
      flavopiridol 30-85 mg/m2 over 24 hours every 3 weeks for 3 cycles. RESULTS:
      Eighteen patients were enrolled at 4 sites in the United States and received
      flavopiridol 30 mg/m2 (n = 3), 50 mg/m2 (n = 6), 70 mg/m2 (n = 3), or 85 mg/m2 (n
      = 6). No dose-limiting toxicities (DLTs) occurred at the 50-mg/m2 or 70-mg/m2
      dose levels. Two patients treated at the 85-mg/m2 dose level experienced
      cardiovascular events that did not meet the criteria for DLT but were fatal in 1
      case, prompting no further flavopiridol dose escalations and establishment of 70
      mg/m2 as the maximum tolerated dose. The most frequently reported adverse events
      across all dose levels combined were nausea (89%), asthenia (67%), and diarrhea
      (56%). Flavopiridol concentrations increased rapidly, reached a plateau, and
      showed a multiphasic decline after the 24-hour infusion. Of 12 patients evaluable
      for efficacy, 8 achieved a partial response, and 4 had stable disease.
      CONCLUSION: Flavopiridol in doses <or= 70 mg/m2 in a 24-hour infusion can safely
      be combined with a 3-hour infusion of paclitaxel 175 mg/m2 and a 1-hour infusion
      of carboplatin AUC 5.

PMID- 18621627
TI  - Serum endothelial monocyte-activating polypeptide-II: a novel biomarker in
      patients with non-small-cell lung cancer.
AB  - BACKGROUND: Endothelial monocyte-activating polypeptide-II (EMAP-II) is a
      proinflammatory cytokine with antiangiogenic properties. Serum EMAP-II levels
      have not been investigated previously in non-small-cell lung cancer (NSCLC). The
      aim of this study was to examine the relationship between serum EMAP-II levels
      and clinicopathologic features, including prognosis, in patients with NSCLC.
      PATIENTS AND METHODS: We measured serum EMAP-II levels in 30 healthy control
      subjects and 48 patients with untreated NSCLC by enzyme linkedimmunosorbent
      assay. RESULTS: Patients with NSCLC had significantly higher serum EMAP-II levels
      than did the control group (492 pg/mL +/- 1126 pg/mL vs. 266 pg/mL +/- 1013
      pg/mL; P = .015). No significant association was found between serum EMAP-II
      levels and various clinicopathologic features (age, smoking history, performance
      status, histopathology, tumor stage, lymph node stage, or distant metastasis).
      Median survival time was 10.13 months (range, 2-53.8 months). The high-EMAP-II
      (>or= 100 pg/mL) group had a shorter survival compared with the low-EMAP-II (<
      100 pg/mL) group (P = .023), and the serum EMAP-II level was still an important
      predictor of survival in a multivariate analysis, along with disease stage.
      CONCLUSION: Our results showed that serum EMAP-II levels are significantly higher
      in patients with NSCLC than in healthy subjects and suggest it is of potential
      prognostic value.

PMID- 18621628
TI  - Assessment of guilt and shame in patients with non-small-cell lung cancer
      compared with patients with breast and prostate cancer.
AB  - PURPOSE: Patients with lung cancer might feel more guilt and shame resulting from
      previous smoking. This study was designed to determine the levels of guilt and
      shame among patients with non-small-cell lung cancer (NSCLC) compared with breast
      and prostate cancer. PATIENTS AND METHODS: Surveys were sent to participants 3
      times (at enrollment, 2 months, and 6 months). Patients were eligible if they had
      stage IV NSCLC, breast cancer, or prostate cancer. The survey included tests of
      generalized guilt, shame, depression, and anxiety as well as guilt, shame, and
      embarrassment related to one's cancer. RESULTS: One hundred seventy-two
      participants completed >or= 1 questionnaire: 96 patients with NSCLC, 30 patients
      with breast cancer, and 46 patients with prostate cancer. Of the patients with
      NSCLC, 91.7% were current or former smokers versus 67.1% of the comparison
      patients. A composite score of embarrassment related to one's cancer (perceived
      cancer-related stigma; PCRS) was higher in patients with NSCLC (P < .01). Mean
      baseline generalized guilt and shame scores were not different among groups and
      did not change over time. A history of smoking correlated with increased levels
      of guilt and shame, regardless of tumor type. A personal identification of past
      behaviors as contributing to cancer correlated with higher levels of guilt,
      shame, anxiety, and depression. Of the patients with NSCLC, 29.5% felt that their
      behaviors contributed to their cancer compared with 10.5% of the comparison
      patients. CONCLUSION: Patients with NSCLC had higher levels of PCRS than patients
      with prostate cancer or breast cancer but not higher baseline levels of shame and
      guilt. Smoking is correlated with higher levels of guilt and shame. A belief that
      one caused one's own cancer is correlated with higher levels of guilt, shame,
      anxiety, and depression. These findings could be translated into an increased
      need for open communication among patients and their providers surrounding issues
      of cancer causation, guilt, shame, depression, and anxiety.

PMID- 18621629
TI  - Hypertrophic osteoarthropathy effectively treated with zoledronic acid.
AB  - Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by digital
      clubbing, arthralgias, and tissue swelling and is frequently described in
      association with bronchogenic carcinoma. The associated pain can be disabling,
      and symptoms are often resistant to conventional analgesic medications. We
      present a patient with HOA of the lower extremities and wrists that developed
      after bronchogenic carcinoma. The pain and swelling completely resolved after a
      single administration of 4 mg of zoledronic acid. The proposed pathogenesis of
      HOA and the mechanisms by which bisphosphonates might alleviate symptoms are
      reviewed.

PMID- 18621632
TI  - Molecular biomarker development for anti-EGFR therapy: moving beyond EGFR
      expression.

PMID- 18621634
TI  - Biomarker validation: in situ analysis of protein expression using
      semiquantitative immunohistochemistry-based techniques.
AB  - Biomarker-driven cancer research is common in the current literature. Much of
      this research is a result of the increase in genomic and proteomic high
      throughput technologies, which have increased our knowledge and also produced an
      abundance of data with unclear clinical significance. Immunohistochemistry-based
      assessment of protein expression is a natural validation method of expression
      profiling data that is easily performed on tissue samples collected prospectively
      or from archived samples. Coupled with tissue microarray technology and the
      increasing number of available automated, quantitative systems to read these
      arrays, we now have an efficient method of validating biomarkers for prognostic
      and predictive capabilities and for the identification of drug development
      targets.

PMID- 18621635
TI  - Colon cancer: update on adjuvant therapy.
AB  - Colon cancer is a public health problem worldwide. Although potentially curable
      at early stages, a substantial number of patients will inevitably present with or
      eventually develop metastatic disease, which is often incurable. Despite the
      progress achieved with the introduction of new cytotoxic agents, recurrence rates
      for patients with resected stage II/III disease remain > 20%. Therefore, a great
      deal of effort and resources have been put into improving early diagnosis and
      prevention tools as well as the efficacy of adjuvant treatment. Oxaliplatin-based
      chemotherapy is now considered the standard of care in node-positive colon
      cancer, but there remains controversy with regard to the indication and type of
      adjuvant treatment in patients with nodenegative disease. Oral fluoropyrimidines
      play a growing role in the management of colorectal cancer and can be currently
      considered an alternative to 5-fluorouracil. Numerous reports have suggested that
      elderly patients benefit equally from chemotherapy, but the growing numbers of
      octogenarian and nonagenarian patients in our clinics, many of whom occasionally
      struggle through treatment, are a reminder of the challenges ahead. Finally, as
      we might have reached a plateau in terms of cytotoxic chemotherapy, numerous
      clinical trials are now focusing on the role of biologic agents in the adjuvant
      setting.

PMID- 18621636
TI  - Association of K-ras mutational status and clinical outcomes in patients with
      metastatic colorectal cancer receiving panitumumab alone.
AB  - BACKGROUND: Identifying predictive biomarkers is important to optimally treat
      patients. This analysis evaluated the association of K-ras, BRAF, and PIK3CA gene
      mutations with tumor resistance to panitumumab alone. PATIENTS AND METHODS: From
      3 phase II panitumumab metastatic colorectal cancer (mCRC) studies, 62 of 533
      patient samples were available. Mutations were identified from genomic DNA by
      sequencing. RESULTS: Of the 62 samples, 24 (38.7%) harbored a K-ras mutation, and
      38 (61.3%) were wild type. In the wild-type K-ras group, 11% of patients had a
      partial response (PR), 53% had stable disease (SD), and 37% had progressive
      disease (PD). In the mutant K-ras group, 21% of patients had SD, and 79% of
      patients had PD; there were no responses. The absence of a K-ras mutation was
      associated with response to panitumumab (PR vs. SD vs. PD; P = .0028). The hazard
      ratio for wild-type versus mutant K-ras was 0.4 (95% CI, 0.2-0.7) for progression
      free survival and 0.5 (95% CI, 0.3-0.9) for overall survival. Four patients had a
      V600E BRAF mutation, and 2 patients had a PIK3CA mutation. CONCLUSION: These data
      suggest that patients with mCRC with activating K-ras mutations are less likely
      to respond to panitumumab alone. The small sample size limits us from defining a
      predictive role of PIK3CA and BRAF mutations for panitumumab treatment.

PMID- 18621637
TI  - Adherence to surveillance guidelines after curative resection for stage II/III
      colorectal cancer.
AB  - PURPOSE: Our aims were to determine adherence to American Society of Clinical
      Oncology (ASCO) guidelines on colorectal cancer (CRC) surveillance and to
      evaluate differences in practice patterns and clinical outcomes between an
      academic institution (Princess Margaret Hospital [PMH]) and a community cancer
      hospital (Credit Valley Hospital [CVH]). PATIENTS AND METHODS: Patients with
      stage II/III CRC who were diagnosed between January 1, 1999, and December 31,
      2001, were identified, and their records were retrospectively reviewed. RESULTS:
      A total of 244 and 97 patients were eligible at PMH and CVH, respectively.
      Surveillance patterns, including blood tests, imaging studies, and colonoscopies,
      were inconsistent with ASCO recommendations in a significant proportion of
      patients. Clinic visits occurred more frequently and imaging studies were more
      commonly ordered at PMH than at CVH (P < .001). In contrast, CVH performed a
      higher median number of blood count and liver function tests (P = .001) per
      patient than PMH. The rates of carcinoembryonic antigen monitoring and
      surveillance colonoscopies were not statistically different between centers (P =
      .67 and P = .43, respectively). There were a total of 70 CRC recurrences: 53
      (75.7%) were detected by surveillance (44 at PMH and 9 at CVH) and 17 (24.3%) by
      patient symptoms (9 at PMH and 8 at CVH). For recurrences detected by
      surveillance, 38% were resectable, whereas only 18% of those detected by symptoms
      were resectable. CONCLUSION: Colorectal cancer surveillance revealed noticeable
      departures from ASCO guidelines, with the academic institution using a more
      intensive surveillance strategy with imaging studies than the community cancer
      center. Surveillance was associated with a higher proportion of resectable tumor
      recurrences than was detection by patient symptoms.

PMID- 18621638
TI  - A decision analysis model predicts the optimal treatment pathway for patients
      with colorectal cancer and resectable synchronous liver metastases.
AB  - BACKGROUND: The estimated 2400 Americans who annually present with colorectal
      cancer and simultaneous resectable liver metastases encounter a wide array of
      surgical and medical treatment options. Because of the large number of possible
      treatment sequences and the absence of clinical trials comparing these various
      pathways, there is no consensus on the optimal therapeutic strategy. MATERIALS
      AND METHODS: To address this issue, a decision-making model was developed
      incorporating all possible combinations of the following treatments: colorectal
      resection, hepatic resection, simultaneous colohepatic resection, and systemic
      chemotherapy. Transition probabilities associated with each treatment were
      determined by systematic review of the literature. Variations in complication
      rates based on the extent of hepatectomy (minor: 1-2 segments vs. major: > 2
      segments) were factored into the model. Sensitivity analyses were performed to
      identify threshold values for study variables that altered the optimal treatment
      pathway. RESULTS: After 10,000 simulated patient trials with no bias toward any
      one initial treatment (ie, current practice conditions), the global calculated 5
      year survival rate was 21%. For simulated patients with moderate hepatic tumor
      burden, only treatment sequences that placed systemic therapy before major
      hepatectomy resulted in improved 5-year survival projections (38% vs. 29%; P =
      .001; odds ratio, 1.82). Initial treatment with simultaneous colohepatic
      resection was only favored when the operative mortality rate was adjusted to <
      0.5%. CONCLUSION: This detailed decision-making analysis predicts that the
      optimal treatment pathway for most patients with colorectal cancer and
      simultaneous resectable liver metastases is preoperative systemic therapy
      followed by colohepatectomy or 2-stage resection. In the era of improved systemic
      therapies, major hepatic resection should be deferred until local and systemic
      disease can been addressed.

PMID- 18621639
TI  - Successful administration of panitumumab alone after severe infusion reaction to
      cetuximab in a patient with metastatic colorectal cancer.
AB  - The administration of monoclonal antibodies (MoAbs) can result in infusion
      reactions of various grades; severe reactions are seen in approximately 3% of
      patients after infusions of cetuximab (fatalities occur in approximately 0.1% of
      patients). We report a case of a patient who had a severe reaction to cetuximab
      (a murine MoAb) who then received panitumumab (a human MoAb) and tolerated it
      without any infusion reaction.

PMID- 18621640
TI  - Intussusception in colorectal cancer.
AB  - Adult intussusception is a rare occurrence and, unlike in childhood, is usually
      associated with an underlying tumor. Although computed tomography (CT) imaging
      can identify an intussusception and point toward a cause, diagnosis is
      challenging if it is only intermittent. When an intussusception presents in the
      context of a known bowel cancer, it is possible to attribute nonspecific
      abdominal symptoms to the malignant process. Herein, we describe 2 cases of
      retrograde intussusception caused by cecal tumors that were not identified on
      preoperative CT scanning, only to be found during surgery. Both patients
      presented with intermittent severe abdominal pain and weight loss, which is not
      usually a feature of cecal cancer without metastases. These cases highlight the
      difficulty of diagnosing intermittent adult intussusception and that atypical
      abdominal pain might herald an otherwise occult colorectal cancer.

PMID- 18621641
TI  - Is XELOX equivalent to FOLFOX or other continuous-infusion 5-fluorouracil
      chemotherapy in metastatic colorectal cancer?
AB  - Continuous-infusion 5-fluorouracil (5-FU)/leucovorin (LV) and oxaliplatin is a
      frequently used regimen in metastatic colorectal cancer. Continuous-infusion 5-FU
      imposes constraints on patients and institutions. Oral fluoropyrimidines that
      mimic continuous-infusion 5-FU are now available and can be combined with
      oxaliplatin. In addition, it has been shown in small randomized trials that oral
      fluoropyrimidines are preferred by patients. Several randomized trials have
      compared continuous-infusion 5-FU/oxaliplatin with the oral fluoropyrimidine
      capecitabine plus oxaliplatin. In all of these trials, noninferiority was
      demonstrated for the use of oral fluoropyrimidines on the predefined endpoints
      such as progression-free survival, overall survival, or response rate. In all
      trials, however, the hazard ratios were always in favor of the use of continuous
      infusion 5-FU/LV even though noninferiority was demonstrated. This could question
      the need to use oral fluoropyrimidines instead of continuous-infusion 5-FU.
      Patient preference, quality of life, and cost of treatment could also be
      considered in this setting, wherein most of the patients are not in a curative
      situation.

PMID- 18621643
TI  - European research, 10 years on.

PMID- 18621644
TI  - Food safety. Arsenic and paddy rice: a neglected cancer risk?

PMID- 18621645
TI  - U.S. graduate training. Top Ph.D. feeder schools are now Chinese.

PMID- 18621646
TI  - U.S. budget. 2008 supplemental helps Fermilab by putting jobs before research.

PMID- 18621647
TI  - Social sciences. Defense, NSF team up on national security research.

PMID- 18621648
TI  - Nuclear control. Iraq embarks on demolition of Saddam-era nuclear labs.

PMID- 18621649
TI  - Acoustical science. Major European cities are quietly missing antinoise deadline.

PMID- 18621650
TI  - University research. Steering Harvard toward collaborative science.

PMID- 18621651
TI  - Bipolar disorder. Poles apart.

PMID- 18621652
TI  - Evolution. Modernizing the modern synthesis.

PMID- 18621653
TI  - Biofuels: effects on land and fire.

PMID- 18621654
TI  - Comment on "Genetically determined differences in learning from errors".
AB  - Klein et al. (Reports, 7 December 2007, p. 1642) used individuals with a
      polymorphism adjacent to the dopamine receptor 2 gene as naturally occurring
      models for reduced brain dopamine receptor density in a probabilistic learning
      task. We raise the concern that this polymorphism resides in the gene for the
      kinase ANKK1, where it causes a nonconservative amino acid exchange.

PMID- 18621655
TI  - Biofuels: one of many claims to resources.

PMID- 18621656
TI  - Genetics. Celebrating spuds.

PMID- 18621657
TI  - Economics. Homo experimentalis Evolves.

PMID- 18621658
TI  - Genetics. Insights into the pathogenesis of autism.

PMID- 18621659
TI  - Engineering. Phase-change materials for electronic memories.

PMID- 18621660
TI  - Paleontology. New tricks with old bones.

PMID- 18621661
TI  - Enzymes without borders: mobilizing substrates, delivering products.
AB  - Many cellular reactions involve both hydrophobic and hydrophilic molecules that
      reside within the chemically distinct environments defined by the phospholipid
      based membranes and the aqueous lumens of cytoplasm and organelles. Enzymes
      performing this type of reaction are required to access a lipophilic substrate
      located in the membranes and to catalyze its reaction with a polar, water-soluble
      compound. Here, we explore the different binding strategies and chemical tricks
      that enzymes have developed to overcome this problem. These reactions can be
      catalyzed by integral membrane proteins that channel a hydrophilic molecule into
      their active site, as well as by water-soluble enzymes that are able to capture a
      lipophilic substrate from the phospholipid bilayer. Many chemical and biological
      aspects of this type of enzymology remain to be investigated and will require the
      integration of protein chemistry with membrane biology.

PMID- 18621662
TI  - Source analysis of the Crandall Canyon, Utah, mine collapse.
AB  - Analysis of seismograms from a magnitude 3.9 seismic event on 6 August 2007 in
      central Utah reveals an anomalous radiation pattern that is contrary to that
      expected for a tectonic earthquake and which is dominated by an implosive
      component. The results show that the seismic event is best modeled as a shallow
      underground collapse. Interestingly, large transverse surface waves require a
      smaller additional noncollapse source component that might represent either
      faulting in the rocks above the mine workings or deformation of the medium
      surrounding the mine. Seismic moment tensor results for nuclear explosions,
      explosion and other mining cavity collapses, and tectonic earthquakes are
      compared, and the separation of the different populations indicates that the
      seismic moment tensor may be used for source-type discrimination.

PMID- 18621664
TI  - High-efficiency organic solar concentrators for photovoltaics.
AB  - The cost of photovoltaic power can be reduced with organic solar concentrators.
      These are planar waveguides with a thin-film organic coating on the face and
      inorganic solar cells attached to the edges. Light is absorbed by the coating and
      reemitted into waveguide modes for collection by the solar cells. We report
      single- and tandem-waveguide organic solar concentrators with quantum
      efficiencies exceeding 50% and projected power conversion efficiencies as high as
      6.8%. The exploitation of near-field energy transfer, solid-state solvation, and
      phosphorescence enables 10-fold increases in the power obtained from photovoltaic
      cells, without the need for solar tracking.

PMID- 18621663
TI  - Identifying autism loci and genes by tracing recent shared ancestry.
AB  - To find inherited causes of autism-spectrum disorders, we studied families in
      which parents share ancestors, enhancing the role of inherited factors. We mapped
      several loci, some containing large, inherited, homozygous deletions that are
      likely mutations. The largest deletions implicated genes, including PCDH10
      (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of
      expression changes in response to neuronal activity, a marker of genes involved
      in synaptic changes that underlie learning. A subset of genes, including NHE9
      (Na+/H+ exchanger 9), showed additional potential mutations in patients with
      unrelated parents. Our findings highlight the utility of "homozygosity mapping"
      in heterogeneous disorders like autism but also suggest that defective regulation
      of gene expression after neural activity may be a mechanism common to seemingly
      diverse autism mutations.

PMID- 18621665
TI  - Optical pumping and vibrational cooling of molecules.
AB  - The methods producing cold molecules from cold atoms tend to leave molecular
      ensembles with substantial residual internal energy. For instance, cesium
      molecules initially formed via photoassociation of cold cesium atoms are in
      several vibrational levels nu of the electronic ground state. We applied a
      broadband femtosecond laser that redistributes the vibrational population in the
      ground state via a few electronic excitation/spontaneous emission cycles. The
      laser pulses are shaped to remove the excitation frequency band of the nu = 0
      level, preventing re-excitation from that state. We observed a fast and efficient
      accumulation ( approximately 70% of the initially detected molecules) in the
      lowest vibrational level, nu = 0, of the singlet electronic state. The validity
      of this incoherent depopulation pumping method is very general and opens exciting
      prospects for laser cooling and manipulation of molecules.

PMID- 18621666
TI  - A positive test of East Antarctica-Laurentia juxtaposition within the Rodinia
      supercontinent.
AB  - The positions of Laurentia and other landmasses in the Precambrian supercontinent
      of Rodinia are controversial. Although geological and isotopic data support an
      East Antarctic fit with western Laurentia, alternative reconstructions favor the
      juxtaposition of Australia, Siberia, or South China. New geologic, age, and
      isotopic data provide a positive test of the juxtaposition with East Antarctica:
      Neodymium isotopes of Neoproterozoic rift-margin strata are similar; hafnium
      isotopes of approximately 1.4-billion-year-old Antarctic-margin detrital zircons
      match those in Laurentian granites of similar age; and a glacial clast of A-type
      granite has a uraniun-lead zircon age of approximately 1440 million years, an
      epsilon-hafnium initial value of +7, and an epsilon-neodymium initial value of
      +4. These tracers indicate the presence of granites in East Antarctica having the
      same age, geochemical properties, and isotopic signatures as the distinctive
      granites in Laurentia.

PMID- 18621667
TI  - Anticrack nucleation as triggering mechanism for snow slab avalanches.
AB  - Snow slab avalanches are believed to begin by the gravity-driven shear failure of
      weak layers in stratified snow. The critical crack length for shear crack
      propagation along such layers should increase without bound as the slope
      decreases. However, recent experiments show that the critical length of
      artificially introduced cracks remains constant or, if anything, slightly
      decreases with decreasing slope. This surprising observation can be understood in
      terms of volumetric collapse of the weak layer during failure, resulting in the
      formation and propagation of mixed-mode anticracks, which are driven
      simultaneously by slope-parallel and slope-normal components of gravity. Such
      fractures may propagate even if crack-face friction impedes downhill sliding of
      the snowpack, indicating a scenario in which two separate conditions have to be
      met for slab avalanche release.

PMID- 18621668
TI  - The high-affinity E. coli methionine ABC transporter: structure and allosteric
      regulation.
AB  - The crystal structure of the high-affinity Escherichia coli MetNI methionine
      uptake transporter, a member of the adenosine triphosphate (ATP)-binding cassette
      (ABC) family, has been solved to 3.7 angstrom resolution. The overall
      architecture of MetNI reveals two copies of the adenosine triphosphatase (ATPase)
      MetN in complex with two copies of the transmembrane domain MetI, with the
      transporter adopting an inward-facing conformation exhibiting widely separated
      nucleotide binding domains. Each MetI subunit is organized around a core of five
      transmembrane helices that correspond to a subset of the helices observed in the
      larger membrane-spanning subunits of the molybdate (ModBC) and maltose (MalFGK)
      ABC transporters. In addition to the conserved nucleotide binding domain of the
      ABC family, MetN contains a carboxyl-terminal extension with a ferredoxin-like
      fold previously assigned to a conserved family of regulatory ligand-binding
      domains. These domains separate the nucleotide binding domains and would
      interfere with their association required for ATP binding and hydrolysis.
      Methionine binds to the dimerized carboxyl-terminal domain and is shown to
      inhibit ATPase activity. These observations are consistent with an allosteric
      regulatory mechanism operating at the level of transport activity, where
      increased intracellular levels of the transported ligand stabilize an inward
      facing, ATPase-inactive state of MetNI to inhibit further ligand translocation
      into the cell.

PMID- 18621669
TI  - Structural basis for specific substrate recognition by the chloroplast signal
      recognition particle protein cpSRP43.
AB  - Secretory and membrane proteins carry amino-terminal signal sequences that, in
      cotranslational targeting, are recognized by the signal recognition particle
      protein SRP54 without sequence specificity. The most abundant membrane proteins
      on Earth are the light-harvesting chlorophyll a/b binding proteins (LHCPs). They
      are synthesized in the cytoplasm, imported into the chloroplast, and
      posttranslationally targeted to the thylakoid membrane by cpSRP, a heterodimer
      formed by cpSRP54 and cpSRP43. We present the 1.5 angstrom crystal structure of
      cpSRP43 characterized by a unique arrangement of chromodomains and ankyrin
      repeats. The overall shape and charge distribution of cpSRP43 resembles the SRP
      RNA, which is absent in chloroplasts. The complex with the internal signal
      sequence of LHCPs reveals that cpSRP43 specifically recognizes a DPLG peptide
      motif. We describe how cpSPR43 adapts the universally conserved SRP system to
      posttranslational targeting and insertion of the LHCP family of membrane
      proteins.

PMID- 18621670
TI  - Genetic determinants of self identity and social recognition in bacteria.
AB  - The bacterium Proteus mirabilis is capable of movement on solid surfaces by a
      type of motility called swarming. Boundaries form between swarming colonies of
      different P. mirabilis strains but not between colonies of a single strain. A
      fundamental requirement for boundary formation is the ability to discriminate
      between self and nonself. We have isolated mutants that form boundaries with
      their parent. The mutations map within a six-gene locus that we term ids for
      identification of self. Five of the genes in the ids locus are required for
      recognition of the parent strain as self. Three of the ids genes are
      interchangeable between strains, and two encode specific molecular identifiers.

PMID- 18621671
TI  - Drug target identification using side-effect similarity.
AB  - Targets for drugs have so far been predicted on the basis of molecular or
      cellular features, for example, by exploiting similarity in chemical structure or
      in activity across cell lines. We used phenotypic side-effect similarities to
      infer whether two drugs share a target. Applied to 746 marketed drugs, a network
      of 1018 side effect-driven drug-drug relations became apparent, 261 of which are
      formed by chemically dissimilar drugs from different therapeutic indications. We
      experimentally tested 20 of these unexpected drug-drug relations and validated 13
      implied drug-target relations by in vitro binding assays, of which 11 reveal
      inhibition constants equal to less than 10 micromolar. Nine of these were tested
      and confirmed in cell assays, documenting the feasibility of using phenotypic
      information to infer molecular interactions and hinting at new uses of marketed
      drugs.

PMID- 18621673
TI  - Ethnic variations in mammographic density: a British multiethnic longitudinal
      study.
AB  - It is not known whether the 20-30% lower breast cancer incidence rates in first
      generation South Asian and Afro-Caribbean women relative to Caucasian women in
      the United Kingdom are reflected in mammographic density. The authors conducted a
      United Kingdom population-based multiethnic study of mammographic density at ages
      50-64 years in 645 women. Data on breast cancer risk factors were obtained using
      a questionnaire/telephone interview. Threshold percent density was assessed on
      5,277 digitized mammograms taken in 1995-2004 and was analyzed using multilevel
      models. Both ethnic minorities were characterized by more protective breast
      cancer risk factor distributions than Caucasians, such as later menarche, shorter
      stature, higher parity, earlier age at first birth, and less use of hormone
      therapy, but they had a higher mean body mass index; the last four factors were
      associated with lower mammographic density. Age-adjusted percent mammographic
      densities in Afro-Caribbeans and South Asians were 5.6% (95% confidence interval
      (CI): 3.5, 7.5) and 5.9% (95% CI: 3.6, 8.0) lower, respectively, than in
      Caucasians. Lower densities were partly attributed to higher body mass index,
      less use of hormone therapy, and a protective reproductive history, but these
      factors did not account entirely for ethnic differences, since fully adjusted
      mean densities were 1.3% (95% CI: -1.3, 3.7) and 3.8% (95% CI: 1.1, 6.3) lower,
      respectively. Ethnic differences in mammographic density are consistent with
      those for breast cancer risk.

PMID- 18621675
TI  - Structure of the alpha2epsilon2 Ni-dependent CO dehydrogenase component of the
      Methanosarcina barkeri acetyl-CoA decarbonylase/synthase complex.
AB  - Ni-dependent carbon monoxide dehydrogenases (Ni-CODHs) are a diverse family of
      enzymes that catalyze reversible CO:CO(2) oxidoreductase activity in acetogens,
      methanogens, and some CO-using bacteria. Crystallography of Ni-CODHs from CO
      using bacteria and acetogens has revealed the overall fold of the Ni-CODH core
      and has suggested structures for the C cluster that mediates CO:CO(2)
      interconversion. Despite these advances, the mechanism of CO oxidation has
      remained elusive. Herein, we report the structure of a distinct class of Ni-CODH
      from methanogenic archaea: the alpha(2)epsilon(2) component from the
      alpha(8)beta(8)gamma(8)delta(8)epsilon(8) CODH/acetyl-CoA decarbonylase/synthase
      complex, an enzyme responsible for the majority of biogenic methane production on
      Earth. The structure of this Ni-CODH component provides support for a hitherto
      unobserved state in which both CO and H(2)O/OH(-) bind to the Ni and the
      exogenous FCII iron of the C cluster, respectively, and offers insight into the
      structures and functional roles of the epsilon-subunit and FeS domain not present
      in nonmethanogenic Ni-CODHs.

PMID- 18621676
TI  - The tumor suppressor genes dachsous and fat modulate different signalling
      pathways by regulating dally and dally-like.
AB  - The activity of different signaling pathways must be precisely regulated during
      development to define the final size and pattern of an organ. The Drosophila
      tumor suppressor genes dachsous (ds) and fat (ft) modulate organ size and pattern
      formation during imaginal disc development. Recent studies have proposed that Fat
      acts through the conserved Hippo signaling pathway to repress the expression of
      cycE, bantam, and diap-1. However, the combined ectopic expression of all of
      these target genes does not account for the hyperplasic phenotypes and patterning
      defects displayed by Hippo pathway mutants. Here, we identify the glypicans dally
      and dally-like as two target genes for both ft and ds acting via the Hippo
      pathway. Dally and Dally-like modulate organ growth and patterning by regulating
      the diffusion and efficiency of signaling of several morphogens such as
      Decapentaplegic, Hedgehog, and Wingless. Our findings therefore provide
      significant insights into the mechanisms by which mutations in the Hippo pathway
      genes can simultaneously alter the activity of several signaling pathways,
      compromising the control of growth and pattern formation.

PMID- 18621677
TI  - A synthetic mammalian gene circuit reveals antituberculosis compounds.
AB  - Synthetic biology provides insight into natural gene-network dynamics and enables
      assembly of engineered transcription circuitries for production of difficult-to
      access therapeutic molecules. In Mycobacterium tuberculosis EthR binds to a
      specific operator (O(ethR)) thereby repressing ethA and preventing EthA-catalyzed
      conversion of the prodrug ethionamide, which increases the resistance of the
      pathogen to this last-line-of-defense treatment. We have designed a synthetic
      mammalian gene circuit that senses the EthR-O(ethR) interaction in human cells
      and produces a quantitative reporter gene expression readout. Challenging of the
      synthetic network with compounds of a rationally designed chemical library
      revealed 2-phenylethyl-butyrate as a nontoxic substance that abolished EthR's
      repressor function inside human cells, in mice, and within M. tuberculosis where
      it triggered derepression of ethA and increased the sensitivity of this pathogen
      to ethionamide. The discovery of antituberculosis compounds by using synthetic
      mammalian gene circuits may establish a new line of defense against multidrug
      resistant M. tuberculosis.

PMID- 18621678
TI  - Divergent sodium channel defects in familial hemiplegic migraine.
AB  - Familial hemiplegic migraine type 3 (FHM3) is a severe autosomal dominant
      migraine disorder caused by mutations in the voltage-gated sodium channel
      Na(V)1.1 encoded by SCN1A. We determined the functional consequences of three
      mutations linked to FHM3 (L263V, Q1489K, and L1649Q) in an effort to identify
      molecular defects that underlie this inherited migraine disorder. Only L263V and
      Q1489K generated quantifiable sodium currents when coexpressed in tsA201 cells
      with the human beta(1) and beta(2) accessory subunits. The third mutant, L1649Q,
      failed to generate measurable whole-cell current because of markedly reduced cell
      surface expression. Compared to WT-Na(V)1.1, Q1489K exhibited increased
      persistent current but also enhanced entry into slow inactivation as well as
      delayed recovery from fast and slow inactivation, thus resulting in a
      predominantly loss-of-function phenotype further demonstrated by a greater loss
      of channel availability during repetitive stimulation. In contrast, L263V
      exhibited gain-of-function features, including delayed entry into, as well as
      accelerated recovery from, fast inactivation; depolarizing shifts in the steady
      state voltage dependence of fast and slow inactivation; increased persistent
      current; and delayed entry into slow inactivation. Notably, the two mutations
      (Q1489K and L1649Q) that exhibited partial or complete loss of function are
      linked to typical FHM, whereas the gain-of-function mutation L263V occurred in a
      family having both FHM and a high incidence of generalized epilepsy. We infer
      from these data that a complex spectrum of Na(V)1.1 defects can cause FHM3. Our
      results also emphasize the complex relationship between migraine and epilepsy and
      provide further evidence that both disorders may share common molecular
      mechanisms.

PMID- 18621679
TI  - Coordinated evolution of the hepatitis C virus.
AB  - Hepatitis C virus is a genetically heterogeneous RNA virus that is a major cause
      of liver disease worldwide. Here, we show that, despite its extensive
      heterogeneity, the evolution of hepatitis C virus is primarily shaped by negative
      selection and that numerous coordinated substitutions in the polyprotein can be
      organized into a scale-free network whose degree of connections between sites
      follows a power-law distribution. This network shares all major properties with
      many complex biological and technological networks. The topological structure and
      hierarchical organization of this network suggest that a small number of amino
      acid sites exert extensive impact on hepatitis C virus evolution. Nonstructural
      proteins are enriched for negatively selected sites of high centrality, whereas
      structural proteins are enriched for positively selected sites located in the
      periphery of the network. The complex network of coordinated substitutions is an
      emergent property of genetic systems with implications for evolution, vaccine
      research, and drug development. In addition to such properties as polymorphism or
      strength of selection, the epistatic connectivity mapped in the network is
      important for typing individual sites, proteins, or entire genetic systems. The
      network topology may help devise molecular intervention strategies for disrupting
      viral functions or impeding compensatory changes for vaccine escape or drug
      resistance mutations. Also, it may be used to find new therapeutic targets, as
      suggested in this study for the NS4A protein, which plays an important role in
      the network.

PMID- 18621680
TI  - The MCK mouse heart model of Friedreich's ataxia: Alterations in iron-regulated
      proteins and cardiac hypertrophy are limited by iron chelation.
AB  - There is no effective treatment for the cardiomyopathy of the most common
      autosomal recessive ataxia, Friedreich's ataxia (FA). The identification of
      potentially toxic mitochondrial (MIT) iron (Fe) deposits in FA suggests that Fe
      plays a role in its pathogenesis. This study used the muscle creatine kinase
      conditional frataxin (Fxn) knockout (mutant) mouse model that reproduces the
      classical traits associated with cardiomyopathy in FA. We examined the mechanisms
      responsible for the increased cardiac MIT Fe loading in mutants. Moreover, we
      explored the effect of Fe chelation on the pathogenesis of the cardiomyopathy.
      Our investigation showed that increased MIT Fe in the myocardium of mutants was
      due to marked transferrin Fe uptake, which was the result of enhanced transferrin
      receptor 1 expression. In contrast to the mitochondrion, cytosolic ferritin
      expression and the proportion of cytosolic Fe were decreased in mutant mice,
      indicating cytosolic Fe deprivation and markedly increased MIT Fe targeting.
      These studies demonstrated that loss of Fxn alters cardiac Fe metabolism due to
      pronounced changes in Fe trafficking away from the cytosol to the mitochondrion.
      Further work showed that combining the MIT-permeable ligand pyridoxal
      isonicotinoyl hydrazone with the hydrophilic chelator desferrioxamine prevented
      cardiac Fe loading and limited cardiac hypertrophy in mutants but did not lead to
      overt cardiac Fe depletion or toxicity. Fe chelation did not prevent decreased
      succinate dehydrogenase expression in the mutants or loss of cardiac function. In
      summary, we show that loss of Fxn markedly alters cellular Fe trafficking and
      that Fe chelation limits myocardial hypertrophy in the mutant.

PMID- 18621681
TI  - Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1,
      the principal cholesterol hydroxylase in the brain.
AB  - By converting cholesterol to 24S-hydroxycholesterol, cytochrome P450 46A1
      (CYP46A1) initiates the major pathway for cholesterol removal from the brain. Two
      crystal structures of CYP46A1 were determined. First is the 1.9-A structure of
      CYP46A1 complexed with a high-affinity substrate cholesterol 3-sulfate (CH-3S).
      The second structure is that of the substrate-free CYP46A1 at 2.4-A resolution.
      CH-3S is bound in the productive orientation and occupies the entire length of
      the banana-shaped hydrophobic active-site cavity. A unique helix B'-C loop
      insertion (residues 116-120) contributes to positioning cholesterol for
      oxygenation catalyzed by CYP46A1. A comparison with the substrate-free structure
      reveals substantial substrate-induced conformational changes in CYP46A1 and
      suggests that structurally distinct compounds could bind in the enzyme active
      site. In vitro assays were performed to characterize the effect of different
      therapeutic agents on cholesterol hydroxylase activity of purified full-length
      recombinant CYP46A1, and several strong inhibitors and modest coactivators of
      CYP46A1 were identified. Structural and biochemical data provide evidence that
      CYP46A1 activity could be altered by exposure to some therapeutic drugs and
      potentially other xenobiotics.

PMID- 18621682
TI  - Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted
      spaces of myoendothelial projections.
AB  - Calcium (Ca(2+)) release through inositol 1,4,5-trisphosphate receptors (IP(3)Rs)
      regulates the function of virtually every mammalian cell. Unlike ryanodine
      receptors, which generate local Ca(2+) events ("sparks") that transmit signals to
      the juxtaposed cell membrane, a similar functional architecture has not been
      reported for IP(3)Rs. Here, we have identified spatially fixed, local Ca(2+)
      release events ("pulsars") in vascular endothelial membrane domains that project
      through the internal elastic lamina to adjacent smooth muscle membranes. Ca(2+)
      pulsars are mediated by IP(3)Rs in the endothelial endoplasmic reticulum of these
      membrane projections. Elevation of IP(3) by the endothelium-dependent
      vasodilator, acetylcholine, increased the frequency of Ca(2+) pulsars, whereas
      blunting IP(3) production, blocking IP(3)Rs, or depleting endoplasmic reticulum
      Ca(2+) inhibited these events. The elementary properties of Ca(2+) pulsars were
      distinct from ryanodine-receptor-mediated Ca(2+) sparks in smooth muscle and from
      IP(3)-mediated Ca(2+) puffs in Xenopus oocytes. The intermediate conductance,
      Ca(2+)-sensitive potassium (K(Ca)3.1) channel also colocalized to the endothelial
      projections, and blockage of this channel caused an 8-mV depolarization.
      Inhibition of Ca(2+) pulsars also depolarized to a similar extent, and blocking
      K(Ca)3.1 channels was without effect in the absence of pulsars. Our results
      support a mechanism of IP(3) signaling in which Ca(2+) release is spatially
      restricted to transmit intercellular signals.

PMID- 18621683
TI  - Respiratory syncytial virus uses a Vps4-independent budding mechanism controlled
      by Rab11-FIP2.
AB  - Respiratory syncytial virus (RSV) infects polarized epithelia, which have tightly
      regulated trafficking because of the separation and maintenance of the apical and
      basolateral membranes. Previously we established a link between the apical
      recycling endosome (ARE) and the assembly of RSV. The current studies tested the
      role of a major ARE-associated protein, Rab11 family interacting protein 2 (FIP2)
      in the virus life cycle. A dominant-negative form of FIP2 lacking its N-terminal
      C2 domain reduced the supernatant-associated RSV titer 1,000-fold and also caused
      the cell-associated virus titer to increase. These data suggested that the FIP2
      C2 mutant caused a failure at the final budding step in the virus life cycle.
      Additionally, truncation of the Rab-binding domain from FIP2 caused its
      accumulation into mature filamentous virions. RSV budding was independent of the
      ESCRT machinery, the only well-defined budding mechanism for enveloped RNA
      viruses. Therefore, RSV uses a virus budding mechanism that is controlled by
      FIP2.

PMID- 18621684
TI  - Cyanobacteriochrome CcaS is the green light receptor that induces the expression
      of phycobilisome linker protein.
AB  - Cyanobacteriochromes are a newly recognized group of photoreceptors that are
      distinct relatives of phytochromes but are found only in cyanobacteria. A
      putative cyanobacteriochrome, CcaS, is known to chromatically regulate the
      expression of the phycobilisome linker gene (cpcG2) in Synechocystis sp. PCC
      6803. In this study, we isolated the chromophore-binding domain of CcaS from
      Synechocystis as well as from phycocyanobilin-producing Escherichia coli. Both
      preparations showed the same reversible photoconversion between a green-absorbing
      form (Pg, lambda(max) = 535 nm) and a red-absorbing form (Pr, lambda(max) = 672
      nm). Mass spectrometry and denaturation analyses suggested that Pg and Pr bind
      phycocyanobilin in a double-bond configuration of C15-Z and C15-E, respectively.
      Autophosphorylation activity of the histidine kinase domain in nearly full-length
      CcaS was up-regulated by preirradiation with green light. Similarly,
      phosphotransfer to the cognate response regulator, CcaR, was higher in Pr than in
      Pg. From these results, we conclude that CcaS phosphorylates CcaR under green
      light and induces expression of cpcG2, leading to accumulation of CpcG2
      phycobilisome as a chromatic acclimation system. CcaS is the first recognized
      green light receptor in the expanded phytochrome superfamily, which includes
      phytochromes and cyanobacteriochromes.

PMID- 18621686
TI  - Alpha-Helix folding in the presence of structural constraints.
AB  - We have investigated the site-specific folding kinetics of a photoswitchable
      cross-linked alpha-helical peptide by using single (13)C = (18)O isotope labeling
      together with time-resolved IR spectroscopy. We observe that the folding times
      differ from site to site by a factor of eight at low temperatures (6 degrees C),
      whereas at high temperatures (45 degrees C), the spread is considerably smaller.
      The trivial sum of the site signals coincides with the overall folding signal of
      the unlabeled peptide, and different sites fold in a noncooperative manner.
      Moreover, one of the sites exhibits a decrease of hydrogen bonding upon folding,
      implying that the unfolded state at low temperature is not unstructured.
      Molecular dynamics simulations at low temperature reveal a stretched-exponential
      behavior which originates from parallel folding routes that start from a
      kinetically partitioned unfolded ensemble. Different metastable structures (i.e.,
      traps) in the unfolded ensemble have a different ratio of loop and helical
      content. Control simulations of the peptide at high temperature, as well as
      without the cross-linker at low temperature, show faster and simpler (i.e.,
      single-exponential) folding kinetics. The experimental and simulation results
      together provide strong evidence that the rate-limiting step in formation of a
      structurally constrained alpha-helix is the escape from heterogeneous traps
      rather than the nucleation rate. This conclusion has important implications for
      an alpha-helical segment within a protein, rather than an isolated alpha-helix,
      because the cross-linker is a structural constraint similar to those present
      during the folding of a globular protein.

PMID- 18621685
TI  - Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus
      arise from nonreactive and polyreactive precursors.
AB  - Persistent autoantibody production in patients with systemic lupus erythematosus
      (SLE) suggests the existence of autoreactive humoral memory, but the frequency of
      self-reactive memory B cells in SLE has not been determined. Here, we report on
      the reactivity of 200 monoclonal antibodies from single IgG+ memory B cells of
      four SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive
      antibodies in this compartment was similar to controls. We found 15% of IgG
      memory B cell antibodies highly reactive and specific for SLE-associated
      extractable nuclear antigens (ENA) Ro52 and La in one patient with serum
      autoantibody titers of the same specificity but not in the other three patients
      or healthy individuals. The germ-line forms of the ENA antibodies were non-self
      reactive or polyreactive with low binding to Ro52, supporting the idea that
      somatic mutations contributed to autoantibody specificity and reactivity.
      Heterogeneity in the frequency of memory B cells expressing SLE-associated
      autoantibodies suggests that this variable may be important in the outcome of
      therapies that ablate this compartment.

PMID- 18621687
TI  - Isolation of a Drosophila amplification origin developmentally activated by
      transcription.
AB  - We exploited the Drosophila Amplicon in Follicle Cells, DAFC-62D, to identify a
      new metazoan amplification origin, ori62. In addition to the origin, DAFC-62D
      contains two other developmental stage-specific binding regions for the Origin
      Recognition Complex (ORC) and the replicative helicase MCM2-7. All three of these
      regions are required for proper amplification. There are two rounds of
      amplification initiation at ori62, and the second round is preceded by
      transcription across ori62. We show by alpha-amanitin inhibition that RNA
      polymerase II (RNAPII) transcription is required to localize MCM2-7 (but not ORC)
      to permit the second round of origin firing. This role for transcription appears
      unique to DAFC-62D, because neither other DAFCs nor ectopic transposons with the
      DAFC-62D replication elements bounded by functional chromatin insulators are
      affected by alpha-amanitin. By sequential chromatin immunoprecipitation, we show
      that the MCM complex and RNAPII are bound to the same 100-500 bp pieces of
      chromatin during late origin firing. These results raise the possibility that
      RNAPII may recruit MCM2-7 at some metazoan replication origins.

PMID- 18621688
TI  - Tools for neuroanatomy and neurogenetics in Drosophila.
AB  - We demonstrate the feasibility of generating thousands of transgenic Drosophila
      melanogaster lines in which the expression of an exogenous gene is reproducibly
      directed to distinct small subsets of cells in the adult brain. We expect the
      expression patterns produced by the collection of 5,000 lines that we are
      currently generating to encompass all neurons in the brain in a variety of
      intersecting patterns. Overlapping 3-kb DNA fragments from the flanking noncoding
      and intronic regions of genes thought to have patterned expression in the adult
      brain were inserted into a defined genomic location by site-specific
      recombination. These fragments were then assayed for their ability to function as
      transcriptional enhancers in conjunction with a synthetic core promoter designed
      to work with a wide variety of enhancer types. An analysis of 44 fragments from
      four genes found that >80% drive expression patterns in the brain; the observed
      patterns were, on average, comprised of <100 cells. Our results suggest that the
      D. melanogaster genome contains >50,000 enhancers and that multiple enhancers
      drive distinct subsets of expression of a gene in each tissue and developmental
      stage. We expect that these lines will be valuable tools for neuroanatomy as well
      as for the elucidation of neuronal circuits and information flow in the fly
      brain.

PMID- 18621689
TI  - Plasma membranes are poised for activation of raft phase coalescence at
      physiological temperature.
AB  - Cell membranes are not randomly organized, but rather are populated by
      fluctuating nanoassemblies of increased translational order termed lipid rafts.
      This lateral heterogeneity can be biophysically extended because cooling
      formaldehyde-isolated plasma membrane preparations results in separation into
      phases similar to the liquid-ordered (Lo) and liquid-disordered (Ld) states seen
      in model membrane systems [Baumgart T, et al. (2007) Proc Natl Acad Sci USA
      104:3165-3170]. In this work we demonstrate that raft clustering, i.e.,
      amplifying underlying raft-based connectivity to a larger scale, makes an
      analogous capacity accessible at 37 degrees C. In plasma membranes at this
      temperature, cholera toxin-mediated cross-linking of the raft ganglioside GM1
      induced the sterol-dependent emergence of a slower diffusing micrometer-scale
      phase that was enriched in cholesterol and selectively reorganized the lateral
      distribution of membrane proteins. Although parallels can be drawn, we argue that
      this raft coalescence in a complex biological matrix cannot be explained by only
      those interactions that define Lo formation in model membranes. Under this light,
      our induction of raft-phase separation suggests that plasma membrane composition
      is poised for selective and functional raft clustering at physiologically
      relevant temperature.

PMID- 18621690
TI  - Uncoupling of behavioral and autonomic responses after lesions of the primate
      orbitofrontal cortex.
AB  - Successful adaptation to changes in an animal's emotional and motivational
      environment depends on behavioral flexibility accompanied by changes in bodily
      responses, e.g., autonomic and endocrine, which support the change in behavior.
      Here, we identify the orbitofrontal cortex (OFC) as pivotal in the flexible
      regulation and coordination of behavioral and autonomic responses during
      adaptation. Using an appetitive Pavlovian task, we demonstrate that OFC lesions
      in the marmoset (i) impair an animal's ability to rapidly suppress its appetitive
      cardiovascular arousal upon termination of a conditioned stimulus and (ii) cause
      an uncoupling of the behavioral and autonomic components of the adaptive response
      after reversal of the reward contingencies. These findings highlight the role of
      the OFC in emotional regulation and are highly relevant to our understanding of
      disorders such as schizophrenia and autism in which uncoupling of emotional
      responses may contribute to the experiential distress and disadvantageous
      behavior associated with these disorders.

PMID- 18621691
TI  - Autophagy is an adaptive response in desmin-related cardiomyopathy.
AB  - A missense mutation in the alphaB-crystallin (CryAB) gene triggers a severe form
      of desmin-related cardiomyopathy (DRCM) characterized by accumulation of
      misfolded proteins. We hypothesized that autophagy increases in response to
      protein aggregates and that this autophagic activity is adaptive. Mutant CryAB
      (CryAB(R120G)) triggered a >2-fold increase in cardiomyocyte autophagic activity,
      and blunting autophagy increased the rate of aggregate accumulation and the
      abundance of insoluble CryAB(R120G)-associated aggregates. Cardiomyocyte
      restricted overexpression of CryAB(R120G) in mice induced intracellular aggregate
      accumulation and systolic heart failure by 12 months. As early as 2 months (well
      before the earliest declines in cardiac function), we detected robust autophagic
      activity. To test the functional significance of autophagic activation, we
      crossed CryAB(R120G) mice with animals harboring heterozygous inactivation of
      beclin 1, a gene required for autophagy. Blunting autophagy in vivo dramatically
      hastened heart failure progression with a 3-fold increase in interstitial
      fibrosis, greater accumulation of polyubiquitinated proteins, larger and more
      extensive intracellular aggregates, accelerated ventricular dysfunction, and
      early mortality. This study reports activation of autophagy in DRCM. Further, our
      findings point to autophagy as an adaptive response in this proteotoxic form of
      heart disease.

PMID- 18621692
TI  - Consistency and functional specialization in the default mode brain network.
AB  - The notion of a "default mode of brain function" has taken on certain relevance
      in human neuroimaging studies and in relation to a network of lateral parietal
      and midline cortical regions that show prominent activity fluctuations during
      passive imaging states, such as rest. In this study, we perform three fMRI
      experiments that demonstrate consistency and specialization in the default mode
      network. Correlated activity fluctuations of default mode network regions are
      identified during (i) eyes-closed spontaneous rest, (ii) activation by moral
      dilemma, and (iii) deactivation by Stroop task performance. Across these imaging
      states, striking uniformity is shown in the basic anatomy of the default mode
      network, but with both tasks clearly and differentially modulating this activity
      compared with spontaneous fluctuations of the network at rest. Against rest,
      moral dilemma is further shown to evoke regionally specific activity increases of
      hypothesized functional relevance. Mapping spontaneous and task-related brain
      activity will help to constrain the meaning of the default mode network. These
      findings are discussed in relation to recent debate on the topic of default modes
      of brain function.

PMID- 18621693
TI  - The RPG gene of Medicago truncatula controls Rhizobium-directed polar growth
      during infection.
AB  - Rhizobia can infect roots of host legume plants and induce new organs called
      nodules, in which they fix atmospheric nitrogen. Infection generally starts with
      root hair curling, then proceeds inside newly formed, intracellular tubular
      structures called infection threads. A successful symbiotic interaction relies on
      infection threads advancing rapidly at their tips by polar growth through
      successive cell layers of the root toward developing nodule primordia. To
      identify a plant component that controls this tip growth process, we
      characterized a symbiotic mutant of Medicago truncatula, called rpg for rhizobium
      directed polar growth. In this mutant, nitrogen-fixing nodules were rarely formed
      due to abnormally thick and slowly progressing infection threads. Root hair
      curling was also abnormal, indicating that the RPG gene fulfils an essential
      function in the process whereby rhizobia manage to dominate the process of
      induced tip growth for root hair infection. Map-based cloning of RPG revealed a
      member of a previously unknown plant-specific gene family encoding putative long
      coiled-coil proteins we have called RRPs (RPG-related proteins) and characterized
      by an "RRP domain" specific to this family. RPG expression was strongly
      associated with rhizobial infection, and the RPG protein showed a nuclear
      localization, indicating that this symbiotic gene constitutes an important
      component of symbiotic signaling.

PMID- 18621694
TI  - A remark on global positioning from local distances.
AB  - Finding the global positioning of points in Euclidean space from a local or
      partial set of pairwise distances is a problem in geometry that emerges naturally
      in sensor networks and NMR spectroscopy of proteins. We observe that the
      eigenvectors of a certain sparse matrix exactly match the sought coordinates.
      This translates to a simple and efficient algorithm that is robust to noisy
      distance data.

PMID- 18621695
TI  - An operational model for mainstreaming ecosystem services for implementation.
AB  - Research on ecosystem services has grown markedly in recent years. However, few
      studies are embedded in a social process designed to ensure effective management
      of ecosystem services. Most research has focused only on biophysical and
      valuation assessments of putative services. As a mission-oriented discipline,
      ecosystem service research should be user-inspired and user-useful, which will
      require that researchers respond to stakeholder needs from the outset and
      collaborate with them in strategy development and implementation. Here we provide
      a pragmatic operational model for achieving the safeguarding of ecosystem
      services. The model comprises three phases: assessment, planning, and management.
      Outcomes of social, biophysical, and valuation assessments are used to identify
      opportunities and constraints for implementation. The latter then are transformed
      into user-friendly products to identify, with stakeholders, strategic objectives
      for implementation (the planning phase). The management phase undertakes and
      coordinates actions that achieve the protection of ecosystem services and ensure
      the flow of these services to beneficiaries. This outcome is achieved via
      mainstreaming, or incorporating the safeguarding of ecosystem services into the
      policies and practices of sectors that deal with land- and water-use planning.
      Management needs to be adaptive and should be institutionalized in a suite of
      learning organizations that are representative of the sectors that are concerned
      with decision-making and planning. By following the phases of our operational
      model, projects for safeguarding ecosystem services are likely to empower
      stakeholders to implement effective on-the-ground management that will achieve
      resilience of the corresponding social-ecological systems.

PMID- 18621696
TI  - Designing payments for ecosystem services: Lessons from previous experience with
      incentive-based mechanisms.
AB  - Payments for ecosystem services (PES) policies compensate individuals or
      communities for undertaking actions that increase the provision of ecosystem
      services such as water purification, flood mitigation, or carbon sequestration.
      PES schemes rely on incentives to induce behavioral change and can thus be
      considered part of the broader class of incentive- or market-based mechanisms for
      environmental policy. By recognizing that PES programs are incentive-based,
      policymakers can draw on insights from the substantial body of accumulated
      knowledge about this class of instruments. In particular, this article offers a
      set of lessons about how the environmental, socioeconomic, political, and dynamic
      context of a PES policy is likely to interact with policy design to produce
      policy outcomes, including environmental effectiveness, cost-effectiveness, and
      poverty alleviation.

PMID- 18621697
TI  - Ecosystem services: from theory to implementation.
AB  - Around the world, leaders are increasingly recognizing ecosystems as natural
      capital assets that supply life-support services of tremendous value. The
      challenge is to turn this recognition into incentives and institutions that will
      guide wise investments in natural capital, on a large scale. Advances are
      required on three key fronts, each featured here: the science of ecosystem
      production functions and service mapping; the design of appropriate finance,
      policy, and governance systems; and the art of implementing these in diverse
      biophysical and social contexts. Scientific understanding of ecosystem production
      functions is improving rapidly but remains a limiting factor in incorporating
      natural capital into decisions, via systems of national accounting and other
      mechanisms. Novel institutional structures are being established for a broad
      array of services and places, creating a need and opportunity for systematic
      assessment of their scope and limitations. Finally, it is clear that formal
      sharing of experience, and defining of priorities for future work, could greatly
      accelerate the rate of innovation and uptake of new approaches.

PMID- 18621698
TI  - Navigating the transition to ecosystem-based management of the Great Barrier
      Reef, Australia.
AB  - We analyze the strategies and actions that enable transitions toward ecosystem
      based management using the recent governance changes of the Great Barrier Reef
      Marine Park as a case study. The interplay among individual actors,
      organizations, and institutions at multiple levels is central in such
      transitions. A flexible organization, the Great Barrier Reef Marine Park
      Authority, was crucial in initiating the transition to ecosystem-based
      management. This agency was also instrumental in the subsequent transformation of
      the governance regime and provided leadership throughout the process. Strategies
      involved internal reorganization and management innovation, leading to an ability
      to coordinate the scientific community, to increase public awareness of
      environmental issues and problems, to involve a broader set of stakeholders, and
      to maneuver the political system for support at critical times. The
      transformation process was induced by increased pressure on the Great Barrier
      Reef (from terrestrial runoff, overharvesting, and global warming) that triggered
      a new sense of urgency to address these challenges. The focus of governance
      shifted from protection of selected individual reefs to stewardship of the larger
      scale seascape. The study emphasizes the significance of stewardship that can
      change patterns of interactions among key actors and allow for new forms of
      management and governance to emerge in response to environmental change. This
      example illustrates that enabling legislations or other social bounds are
      essential, but not sufficient for shifting governance toward adaptive
      comanagement of complex marine ecosystems.

PMID- 18621699
TI  - Accounting for ecosystem services as a way to understand the requirements for
      sustainable development.
AB  - Millennium Ecosystem Assessment documented the importance of ecosystem services.
      It is therefore important that these services are included in our economic
      accounts (Standard National Accounts), as long as we believe that these accounts
      should tell us something about our wellbeing. This requires measures of the
      ecosystem assets and their accounting prices. This article discusses how the
      concept of inclusive wealth can be exploited for creating such accounts.

PMID- 18621700
TI  - Ecological and socioeconomic effects of China's policies for ecosystem services.
AB  - To address devastating environmental crises and to improve human well-being,
      China has been implementing a number of national policies on payments for
      ecosystem services. Two of them, the Natural Forest Conservation Program (NFCP)
      and the Grain to Green Program (GTGP), are among the biggest programs in the
      world because of their ambitious goals, massive scales, huge payments, and
      potentially enormous impacts. The NFCP conserves natural forests through logging
      bans and afforestation with incentives to forest enterprises, whereas the GTGP
      converts cropland on steep slopes to forest and grassland by providing farmers
      with grain and cash subsidies. Overall ecological effects are beneficial, and
      socioeconomic effects are mostly positive. Whereas there are time lags in
      ecological effects, socioeconomic effects are more immediate. Both the NFCP and
      the GTGP also have global implications because they increase vegetative cover,
      enhance carbon sequestration, and reduce dust to other countries by controlling
      soil erosion. The future impacts of these programs may be even bigger. Extended
      payments for the GTGP have recently been approved by the central government for
      up to 8 years. The NFCP is likely to follow suit and receive renewed payments. To
      make these programs more effective, we recommend systematic planning, diversified
      funding, effective compensation, integrated research, and comprehensive
      monitoring. Effective implementation of these programs can also provide important
      experiences and lessons for other ecosystem service payment programs in China and
      many other parts of the world.

PMID- 18621701
TI  - Global mapping of ecosystem services and conservation priorities.
AB  - Global efforts to conserve biodiversity have the potential to deliver economic
      benefits to people (i.e., "ecosystem services"). However, regions for which
      conservation benefits both biodiversity and ecosystem services cannot be
      identified unless ecosystem services can be quantified and valued and their areas
      of production mapped. Here we review the theory, data, and analyses needed to
      produce such maps and find that data availability allows us to quantify imperfect
      global proxies for only four ecosystem services. Using this incomplete set as an
      illustration, we compare ecosystem service maps with the global distributions of
      conventional targets for biodiversity conservation. Our preliminary results show
      that regions selected to maximize biodiversity provide no more ecosystem services
      than regions chosen randomly. Furthermore, spatial concordance among different
      services, and between ecosystem services and established conservation priorities,
      varies widely. Despite this lack of general concordance, "win-win" areas-regions
      important for both ecosystem services and biodiversity-can be usefully
      identified, both among ecoregions and at finer scales within them. An ambitious
      interdisciplinary research effort is needed to move beyond these preliminary and
      illustrative analyses to fully assess synergies and trade-offs in conserving
      biodiversity and ecosystem services.

PMID- 18621702
TI  - An ecosystem services framework to support both practical conservation and
      economic development.
AB  - The core idea of the Millennium Ecosystem Assessment is that the human condition
      is tightly linked to environmental condition. This assertion suggests that
      conservation and development projects should be able to achieve both ecological
      and social progress without detracting from their primary objectives. Whereas
      "win-win" projects that achieve both conservation and economic gains are a
      commendable goal, they are not easy to attain. An analysis of World Bank projects
      with objectives of alleviating poverty and protecting biodiversity revealed that
      only 16% made major progress on both objectives. Here, we provide a framework for
      anticipating win-win, lose-lose, and win-lose outcomes as a result of how people
      manage their ecosystem services. This framework emerges from detailed
      explorations of several case studies in which biodiversity conservation and
      economic development coincide and cases in which there is joint failure. We
      emphasize that scientific advances around ecosystem service production functions,
      tradeoffs among multiple ecosystem services, and the design of appropriate
      monitoring programs are necessary for the implementation of conservation and
      development projects that will successfully advance both environmental and social
      goals. The potentially bright future of jointly advancing ecosystem services,
      conservation, and human well-being will be jeopardized unless a global monitoring
      effort is launched that uses the many ongoing projects as a grand experiment.

PMID- 18621703
TI  - Efficiency of incentives to jointly increase carbon sequestration and species
      conservation on a landscape.
AB  - We develop an integrated model to predict private land-use decisions in response
      to policy incentives designed to increase the provision of carbon sequestration
      and species conservation across heterogeneous landscapes. Using data from the
      Willamette Basin, Oregon, we compare the provision of carbon sequestration and
      species conservation under five simple policies that offer payments for
      conservation. We evaluate policy performance compared with the maximum feasible
      combinations of carbon sequestration and species conservation on the landscape
      for various conservation budgets. None of the conservation payment policies
      produce increases in carbon sequestration and species conservation that approach
      the maximum potential gains on the landscape. Our results show that policies
      aimed at increasing the provision of carbon sequestration do not necessarily
      increase species conservation and that highly targeted policies do not
      necessarily do as well as more general policies.

PMID- 18621704
TI  - In silico identified CCR4 antagonists target regulatory T cells and exert
      adjuvant activity in vaccination.
AB  - Adjuvants are substances that enhance immune responses and thus improve the
      efficacy of vaccination. Few adjuvants are available for use in humans, and the
      one that is most commonly used (alum) often induces suboptimal immunity for
      protection against many pathogens. There is thus an obvious need to develop new
      and improved adjuvants. We have therefore taken an approach to adjuvant discovery
      that uses in silico modeling and structure-based drug-design. As proof-of
      principle we chose to target the interaction of the chemokines CCL22 and CCL17
      with their receptor CCR4. CCR4 was posited as an adjuvant target based on its
      expression on CD4(+)CD25(+) regulatory T cells (Tregs), which negatively regulate
      immune responses induced by dendritic cells (DC), whereas CCL17 and CCL22 are
      chemotactic agents produced by DC, which are crucial in promoting contact between
      DC and CCR4(+) T cells. Molecules identified by virtual screening and molecular
      docking as CCR4 antagonists were able to block CCL22- and CCL17-mediated
      recruitment of human Tregs and Th2 cells. Furthermore, CCR4 antagonists enhanced
      DC-mediated human CD4(+) T cell proliferation in an in vitro immune response
      model and amplified cellular and humoral immune responses in vivo in experimental
      models when injected in combination with either Modified Vaccinia Ankara
      expressing Ag85A from Mycobacterium tuberculosis (MVA85A) or recombinant
      hepatitis B virus surface antigen (rHBsAg) vaccines. The significant adjuvant
      activity observed provides good evidence supporting our hypothesis that CCR4 is a
      viable target for rational adjuvant design.

PMID- 18621705
TI  - Flavin-dependent thymidylate synthase X limits chromosomal DNA replication.
AB  - We have investigated the hitherto unexplored possibility that differences in the
      catalytic efficiencies of thymidylate synthases ThyX and ThyA, enzymes that
      produce the essential DNA precursor dTMP, have influenced prokaryotic genome
      evolution. We demonstrate that DNA replication speed in bacteria and archaea that
      contain the low-activity ThyX enzyme is up to 10-fold decreased compared with
      species that contain the catalytically more efficient ThyA. Our statistical
      studies of >400 genomes indicated that ThyA proteins are preferred for the
      replication of large genomes, providing further evidence that the thymidylate
      metabolism is limiting expansion of prokaryotic genomes. Because both ThyX and
      ThyA participate in frequent reciprocal gene replacement events, our observations
      indicate that the bacterial metabolism continues to modulate the size and
      composition of prokaryotic genomes. We also propose that the increased kinetic
      efficiency of thymidylate synthesis has contributed to extending the prokaryotic
      evolutionary potential.

PMID- 18621706
TI  - The maternal-effect, selfish genetic element Medea is associated with a composite
      Tc1 transposon.
AB  - Maternal-Effect Dominant Embryonic Arrest ("Medea") factors are selfish nuclear
      elements that combine maternal-lethal and zygotic-rescue activities to gain a
      postzygotic survival advantage. We show that Medea(1) activity in Tribolium
      castaneum is associated with a composite Tc1 transposon inserted just downstream
      of the neurotransmitter reuptake symporter bloated tubules (blot), whose
      Drosophila ortholog has both maternal and zygotic functions. The 21.5-kb
      insertion contains defective copies of elongation initiation factor-3, ATP
      synthase subunit C, and an RNaseD-related gene, as well as a potentially intact
      copy of a prokaryotic DUF1703 gene. Sequence comparisons suggest that the current
      distribution of Medea(1) reflects global emanation after a single transpositional
      event in recent evolutionary time. The Medea system in Tribolium represents an
      unusual type of intragenomic conflict and could provide a useful vehicle for
      driving desirable genes into populations.

PMID- 18621707
TI  - Subnanometer-resolution electron cryomicroscopy-based domain models for the
      cytoplasmic region of skeletal muscle RyR channel.
AB  - The skeletal muscle Ca(2+) release channel (RyR1), a homotetramer, regulates the
      release of Ca(2+) from the sarcoplasmic reticulum to initiate muscle contraction.
      In this work, we have delineated the RyR1 monomer boundaries in a subnanometer
      resolution electron cryomicroscopy (cryo-EM) density map. In the cytoplasmic
      region of each RyR1 monomer, 36 alpha-helices and 7 beta-sheets can be resolved.
      A beta-sheet was also identified close to the membrane-spanning region that
      resembles the cytoplasmic pore structures of inward rectifier K(+) channels.
      Three structural folds, generated for amino acids 12-565 using comparative
      modeling and cryo-EM density fitting, localize close to regions implicated in
      communication with the voltage sensor in the transverse tubules. Eleven of the 15
      disease-related residues for these domains are mapped to the surface of these
      models. Four disease-related residues are found in a basin at the interfaces of
      these regions, creating a pocket in which the immunophilin FKBP12 can fit. Taken
      together, these results provide a structural context for both channel gating and
      the consequences of certain malignant hyperthermia and central core disease
      associated mutations in RyR1.

PMID- 18621708
TI  - A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies
      unexpected roles for TCF transcription factors in cancer.
AB  - The Wnt family of secreted proteins coordinate cell fate decision-making in a
      broad range of developmental and homeostatic contexts. Corruption of Wnt signal
      transduction pathways frequently results in degenerative diseases and cancer. We
      have used an iterative genome-wide screening strategy that employs multiple
      nonredundant RNAi reagents to identify mammalian genes that participate in
      Wnt/beta-catenin pathway response. Among the genes that were assigned high
      confidence scores are two members of the TCF/LEF family of DNA-binding proteins
      that control the transcriptional output of the pathway. Surprisingly, we found
      that the presumed cancer-promoting gene TCF7L2 functions instead as a
      transcriptional repressor that restricts colorectal cancer (CRC) cell growth.
      Mutations in TCF7L2 identified from cancer genome sequencing efforts abolish its
      ability to function as a transcriptional regulator and result in increased CRC
      cell growth. We describe a growth-promoting transcriptional program that is
      likely activated in CRC tumors with compromised TCF7L2 function. Taken together,
      the results from our screen and studies focused on members of the TCF/LEF gene
      family refine our understanding of how aberrant Wnt pathway activation sustains
      CRC growth.

PMID- 18621709
TI  - Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and
      blood-testis barrier restructuring during spermatogenesis.
AB  - The Par3/Par6/aPKC and the CRB3/Pals1/PATJ polarity complexes are involved in
      regulating apical ectoplasmic specialization (ES) and blood-testis barrier (BTB)
      restructuring in the testis. Par6 was a component of the apical ES and the BTB.
      However, its level was considerably diminished at both sites at stage VIII of the
      cycle. Par6 also formed a stable complex with Pals1 and JAM-C (a component of the
      apical ES) in normal testes. When rats were treated with adjudin to induce apical
      ES restructuring without compromising the BTB, Par6 staining virtually
      disappeared at the apical ES in misaligned spermatids before their depletion.
      Additionally, the Par6/Pals1 complex became tightly associated with Src kinase,
      rendering a loss of association of the Par6/Pals1 complex with JAM-C, thereby
      destabilizing apical ES to facilitate spermatid loss. Primary Sertoli cell
      cultures with established functional BTB, but without apical ES, were next used
      to assess the Par6-based complex on BTB dynamics. When either Par6 or Par3 was
      knocked down by RNAi in Sertoli cell epithelium, a significant loss of the
      corresponding protein by approximately 60% in cells vs. controls was detected,
      alongside with a decline in aPKC after Par6, but not Par3, knockdown. This Par3
      or Par6 knockdown also led to a transient loss of selected BTB proteins at the
      cell-cell interface, thereby compromising the BTB integrity. These findings
      illustrate that the Par6/Par3-based polarity complex likely coordinates the
      events of apical ES and BTB restructuring that take place concurrently at the
      opposing ends of adjacent Sertoli cells in the seminiferous epithelium during
      spermatogenesis.

PMID- 18621710
TI  - The role of nanostructure in the wetting behavior of mixed-monolayer-protected
      metal nanoparticles.
AB  - Self-assembled monolayer-protected nanoparticles are promising candidates for
      applications, such as sensing and drug delivery, in which the molecular ligands'
      interactions with the surrounding environment play a crucial role. We recently
      showed that, when gold nanoparticles are coated with a binary mixture of
      immiscible ligands, ordered ribbon-like domains of alternating composition
      spontaneously form and that their width is comparable with the size of a single
      solvent molecule. It is usually assumed that nanoparticles' solubility depends
      solely on the core size and on the molecular composition of the ligand shell.
      Here, we show that this is not always the case. We find that the ligand shell
      morphology affects the solubility of these nanoparticles almost as much as the
      molecular composition. A possible explanation is offered through a molecular
      dynamics analysis of the surface energy of monolayers differing only in their
      domain structure. We find that the surface free energy of such model systems can
      vary significantly as a function of ordering, even at fixed composition. This
      combined experimental and theoretical study provides a unique insight into
      wetting phenomena at the nano- and subnanometer scale.

PMID- 18621711
TI  - Evolution of an RNP assembly system: a minimal SMN complex facilitates formation
      of UsnRNPs in Drosophila melanogaster.
AB  - In vertebrates, assembly of spliceosomal uridine-rich small nuclear
      ribonucleoproteins (UsnRNPs) is mediated by the SMN complex, a macromolecular
      entity composed of the proteins SMN and Gemins 2-8. Here we have studied the
      evolution of this machinery using complete genome assemblies of multiple model
      organisms. The SMN complex has gained complexity in evolution by a blockwise
      addition of Gemins onto an ancestral core complex composed of SMN and Gemin2. In
      contrast to this overall evolutionary trend to more complexity in metazoans,
      orthologs of most Gemins are missing in dipterans. In accordance with these
      bioinformatic data a previously undescribed biochemical purification strategy
      elucidated that the dipteran Drosophila melanogaster contains an SMN complex of
      remarkable simplicity. Surprisingly, this minimal complex not only mediates the
      assembly reaction in a manner very similar to its vertebrate counterpart, but
      also prevents misassembly onto nontarget RNAs. Our data suggest that only a
      minority of Gemins are required for the assembly reaction per se, whereas others
      may serve additional functions in the context of UsnRNP biogenesis. The evolution
      of the SMN complex is an interesting example of how the simplification of a
      biochemical process contributes to genome compaction.

PMID- 18621712
TI  - The relationship between dNTP pool levels and mutagenesis in an Escherichia coli
      NDP kinase mutant.
AB  - Loss of nucleoside diphosphate kinase (Ndk) function in Escherichia coli results
      in an increased frequency of spontaneous mutation and an imbalance in dNTP pool
      levels. It is presumed that the imbalance in dNTP pool levels is responsible for
      the mutator phenotype of an E. coli ndk mutant. A human homologue of Ndk and
      potential suppressor of tumor metastasis, nm23-H2, can complement the mutagenic
      phenotype of an E. coli ndk mutant. Here, we show that the antimutagenic property
      of nm23-H2 in E. coli is independent of dNTP pool levels, indicating that dNTP
      pool imbalance is not responsible for the mutator phenotype associated with the
      loss of ndk function. We have identified multiple genetic interactions between
      ndk and genes involved in the metabolism of dUTP, a potentially mutagenic
      precursor of thymidine biosynthesis. We show that loss of ndk function is
      synergistic with a dut-1 mutation and synthetically lethal with the loss of
      thymidine kinase function. Our results suggest that Ndk prevents the accumulation
      of dUTP in vivo. Based on these results and biochemical studies of Ndk, we
      propose that the mutagenic phenotype of an ndk mutant is caused by excess
      misincorporation of uracil in place of thymidine combined with a defect in the
      uracil base excision pathway.

PMID- 18621713
TI  - Fine-scale mapping of recombination rate in Drosophila refines its correlation to
      diversity and divergence.
AB  - Regional rates of recombination often correlate with levels of nucleotide
      diversity, and either selective or neutral hypotheses can explain this
      relationship. Regional recombination rates also correlate with nucleotide
      differences between human and chimpanzee, consistent with models where
      recombination is mutagenic; however, a lack of correlation is observed in the
      Drosophila melanogaster group, consistent with models invoking natural selection.
      Here, we revisit the relationship among recombination, diversity, and
      interspecies difference by generating empirical estimates of these parameters in
      Drosophila pseudoobscura. To measure recombination rate, we genotyped 1,294
      backcross hybrids at 50 markers across the largest assembled linkage group in
      this species. Genome-wide diversity was estimated by sequencing a second isolate
      of D. pseudoobscura at shallow coverage. Alignment to the sequenced genome of the
      closely related species, Drosophila persimilis, provided nucleotide site
      orthology. Our findings demonstrate that scale is critical in determining
      correlates to recombination rate: fine-scale cross-over rate estimates are far
      stronger predictors of both diversity and interspecies difference than broad
      scale estimates. The correlation of fine-scale recombination rate to diversity
      and interspecies difference appears to be genome-wide, evidenced by examination
      of an X-linked region in greater detail. Because we observe a strong correlation
      of cross-over rate with interspecies difference, even after correcting for
      segregating ancestral variation, we suggest that both mutagenic and selective
      forces generate these correlations, the latter in regions of low crossing over.
      We propose that it is not cross-overs per se that are mutagenic, but rather
      repair of DNA double-strand break precursors via crossing over and gene
      conversion.

PMID- 18621714
TI  - FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning,
      remodeling, and functions in adipose tissue.
AB  - Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life,
      and the interplay between these two processes is communicated by multiple
      factors. Here we show that in a transgenic mouse model, increased expression of
      forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular
      patterning, and functions. White and brown adipose tissues contain a considerably
      high density of microvessels appearing as vascular plexuses, which show
      redistribution of vascular smooth muscle cells and pericytes. Dysfunction of
      these primitive vessels is reflected by impairment of skin wound healing. We
      further provide a mechanistic insight of the vascular phenotype by showing that
      FOXC2 controls Ang-2 expression by direct activation of its promoter in
      adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses
      this vascular phenotype. Thus, the FOXC2-Ang-2 signaling system is crucial for
      controlling adipose vascular function, which is part of an adaptation to
      increased adipose tissue metabolism.

PMID- 18621715
TI  - A Cre-loxP-based mouse model for conditional somatic gene expression and
      knockdown in vivo by using avian retroviral vectors.
AB  - Site- and time-specific somatic gene transfer by using the avian sarcoma-leukosis
      retrovirus RCAS (replication-competent avian sarcoma-leukosis virus long terminal
      repeat with splice acceptor) has been shown to be a powerful tool to analyze gene
      function in vivo. RCAS retroviruses that express the avian subgroup A envelope
      transduce only mammalian cells genetically engineered to express the avian
      retroviral receptor, tumor virus A (TVA). Here, we generated a knockin mouse line
      termed LSL-R26(Tva-lacZ) with concomitant conditional expression of TVA and lacZ
      by targeting the Rosa26 locus. A loxP-flanked transcriptional stop cassette was
      used for conditional activation of TVA and LacZ expression in a Cre-recombinase
      dependent manner. To demonstrate the ability of this system for conditional
      somatic gene transfer in vivo, we directed TVA expression to the pancreas.
      Introduction of an RCAS vector with Bryan-RSV polymerase and subgroup A envelope
      [RCASBP(A)] carrying oncogenic Kras(G12D) induced focal ductal pancreatic lesions
      that recapitulate human pancreatic intraepithelial neoplasias that progress to
      pancreatic ductal adenocarcinomas. TVA-mediated infection of genetically
      engineered mice with endogenous expression of Kras(G12D) in pancreatic progenitor
      cells by using RCASBP(A) virus carrying a short hairpin RNA directed against
      murine TP53, resulted in dramatically enhanced progression to invasive
      adenocarcinomas. These results show that conditional expression of TVA enables
      spatiotemporal gene expression and knockdown in a small subset of somatic cells
      in vivo. Therefore, it closely models carcinogenesis in humans where tumors
      evolve from somatic gene mutations in developmentally normal cells. Combined with
      the growing number of Cre expression models, RCAS-TVA-based gene expression and
      knockdown systems open up promising perspectives for analysis of gene function in
      a time-controlled and tissue-specific fashion in vitro and in vivo.

PMID- 18621716
TI  - Amide bonds assemble pili on the surface of bacilli.
AB  - Pilin precursors are the building blocks of pili on the surface of Gram-positive
      bacteria; however, the assembly mechanisms of these adhesive fibers are unknown.
      Here, we describe the chemical bonds that assemble BcpA pilin subunits on the
      surface of Bacillus cereus. Sortase D cleaves BcpA precursor between the
      threonine (T) and the glycine (G) residues of its LPXTG sorting signal and
      catalyzes formation of an amide bond between threonine (T) of the sorting signal
      and lysine (K) in the YPKN motif of another BcpA subunit. Three CNA B domains of
      BcpA generate intramolecular amide bonds, and one of these contributes also to
      pilus formation. Conservation of catalysts and structural elements in pilin
      precursors in Gram-positive bacteria suggests a universal mechanism of fiber
      assembly.

PMID- 18621717
TI  - Distinct conformational changes in beta-arrestin report biased agonism at seven
      transmembrane receptors.
AB  - Beta-arrestins critically regulate G protein-coupled receptors (GPCRs), also
      known as seven-transmembrane receptors (7TMRs), both by inhibiting classical G
      protein signaling and by initiating distinct beta-arrestin-mediated signaling.
      The recent discovery of beta-arrestin-biased ligands and receptor mutants has
      allowed characterization of these independent "G protein-mediated" and "beta
      arrestin-mediated" signaling mechanisms of 7TMRs. However, the molecular
      mechanisms underlying the dual functions of beta-arrestins remain unclear. Here,
      using an intramolecular BRET (bioluminescence resonance energy transfer)-based
      biosensor of beta-arrestin 2 and a combination of biased ligands and/or biased
      mutants of three different 7TMRs, we provide evidence that beta-arrestin can
      adopt multiple "active" conformations. Surprisingly, phosphorylation-deficient
      mutants of the receptors are also capable of directing similar conformational
      changes in beta-arrestin as is the wild-type receptor. This indicates that
      distinct receptor conformations induced and/or stabilized by different ligands
      can promote distinct and functionally specific conformations in beta-arrestin
      even in the absence of receptor phosphorylation. Our data thus highlight another
      interesting aspect of 7TMR signaling--i.e., functionally specific receptor
      conformations can be translated to downstream effectors such as beta-arrestins,
      thereby governing their functional specificity.

PMID- 18621718
TI  - Structures of synthetic O-antigen fragments from serotype 2a Shigella flexneri in
      complex with a protective monoclonal antibody.
AB  - The anti-LPS IgG mAb F22-4, raised against Shigella flexneri serotype 2a
      bacteria, protects against homologous, but not heterologous, challenge in an
      experimental animal model. We report the crystal structures of complexes formed
      between Fab F22-4 and two synthetic oligosaccharides, a decasaccharide and a
      pentadecasaccharide that were previously shown to be both immunogenic and
      antigenic mimics of the S. flexneri serotype 2a O-antigen. F22-4 binds to an
      epitope contained within two consecutive 2a serotype pentasaccharide repeat units
      (RU). Six sugar residues from a contiguous nine-residue segment make direct
      contacts with the antibody, including the nonreducing rhamnose and both branching
      glucosyl residues from the two RUs. The glucosyl residue, whose position of
      attachment to the tetrasaccharide backbone of the RU defines the serotype 2a O
      antigen, is critical for recognition by F22-4. Although the complete
      decasaccharide is visible in the electron density maps, the last four
      pentadecasaccharide residues from the reducing end, which do not contact the
      antibody, could not be traced. Although considerable mobility in the free
      oligosaccharides can thus be expected, the conformational similarity between the
      individual RUs, both within and between the two complexes, suggests that short
      range transient ordering to a helical conformation might occur in solution.
      Although the observed epitope includes the terminal nonreducing residue, binding
      to internal epitopes within the polysaccharide chain is not precluded. Our
      results have implications for vaccine development because they suggest that a
      minimum of two RUs of synthetic serotype 2a oligosaccharide is required for
      optimal mimicry of O-Ag epitopes.

PMID- 18621720
TI  - A protein from the salivary glands of the pea aphid, Acyrthosiphon pisum, is
      essential in feeding on a host plant.
AB  - In feeding, aphids inject saliva into plant tissues, gaining access to phloem sap
      and eliciting (and sometimes overcoming) plant responses. We are examining the
      involvement, in this aphid-plant interaction, of individual aphid proteins and
      enzymes, as identified in a salivary gland cDNA library. Here, we focus on a
      salivary protein we have arbitrarily designated Protein C002. We have shown, by
      using RNAi-based transcript knockdown, that this protein is important in the
      survival of the pea aphid (Acyrthosiphon pisum) on fava bean, a host plant. Here,
      we further characterize the protein, its transcript, and its gene, and we study
      the feeding process of knockdown aphids. The encoded protein fails to match any
      protein outside of the family Aphididae. By using in situ hybridization and
      immunohistochemistry, the transcript and the protein were localized to a subset
      of secretory cells in principal salivary glands. Protein C002, whose sequence
      contains an N-terminal secretion signal, is injected into the host plant during
      aphid feeding. By using the electrical penetration graph method on c002-knockdown
      aphids, we find that the knockdown affects several aspects of foraging and
      feeding, with the result that the c002-knockdown aphids spend very little time in
      contact with phloem sap in sieve elements. Thus, we infer that Protein C002 is
      crucial in the feeding of the pea aphid on fava bean.

PMID- 18621719
TI  - The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more
      elaborate and diverse than found in any known metazoan.
AB  - Tyrosine kinase signaling has long been considered a hallmark of intercellular
      communication, unique to multicellular animals. Our genomic analysis of the
      unicellular choanoflagellate Monosiga brevicollis discovers a remarkable count of
      128 tyrosine kinases, 38 tyrosine phosphatases, and 123 phosphotyrosine (pTyr)
      binding SH2 proteins, all higher counts than seen in any metazoan. This elaborate
      signaling network shows little orthology to metazoan counterparts yet displays
      many innovations reminiscent of metazoans. These include extracellular domains
      structurally related to those of metazoan receptor kinases, alternative methods
      for membrane anchoring and phosphotyrosine interaction in cytoplasmic kinases,
      and domain combinations that link kinases to small GTPase signaling and
      transcription. These proteins also display a wealth of combinations of known
      signaling domains. This uniquely divergent and elaborate signaling network
      illuminates the early evolution of pTyr signaling, explores innovative ways to
      traverse the cellular signaling circuitry, and shows extensive convergent
      evolution, highlighting pervasive constraints on pTyr signaling.

PMID- 18621721
TI  - Force-dependent hopping rates of RNA hairpins can be estimated from accurate
      measurement of the folding landscapes.
AB  - The sequence-dependent folding landscapes of nucleic acid hairpins reflect much
      of the complexity of biomolecular folding. Folding trajectories, generated by
      using single-molecule force-clamp experiments by attaching semiflexible polymers
      to the ends of hairpins, have been used to infer their folding landscapes. Using
      simulations and theory, we study the effect of the dynamics of the attached
      handles on the handle-free RNA free-energy profile F(o)(eq)(z(m)), where z(m) is
      the molecular extension of the hairpin. Accurate measurements of F(o)(eq)(z(m))
      requires stiff polymers with small L/l(p), where L is the contour length of the
      handle, and l(p) is the persistence length. Paradoxically, reliable estimates of
      the hopping rates can only be made by using flexible handles. Nevertheless, we
      show that the equilibrium free-energy profile F(o)(eq)(z(m)) at an external
      tension f(m), the force (f) at which the folded and unfolded states are equally
      populated, in conjunction with Kramers' theory, can provide accurate estimates of
      the force-dependent hopping rates in the absence of handles at arbitrary values
      of f. Our theoretical framework shows that z(m) is a good reaction coordinate for
      nucleic acid hairpins under tension.

PMID- 18621722
TI  - Class 1A PI3K regulates vessel integrity during development and tumorigenesis.
AB  - PI3K is important in the regulation of growth, proliferation, and survival of
      tumor cells. We show that class 1A PI3K is also critical in the tumor
      microenvironment by regulating the integrity of the tumor vasculature. Using
      Tie2Cre-mediated deletion of the PI3K regulatory subunits (p85alpha, p55alpha,
      p50alpha, and p85beta), we generated mice with endothelial cell-specific loss of
      class 1A PI3K. Complete loss of all subunits caused acute embryonic lethality at
      E11.5 due to hemorrhaging, whereas retention of a single p85alpha allele yielded
      viable mice that survived to adulthood. These heterozygous mice exhibited no
      vascular defects until challenged with a pathological insult, such as tumor cells
      or high levels of VEGF. Under these pathological conditions, heterozygous mice
      exhibited localized vascular abnormalities, including vessel leakage and the
      inability to maintain large vessels, which caused a deceleration of
      tumorigenesis. Furthermore, we show that a PI3K inhibitor can mimic the effects
      of class 1A PI3K loss, which suggests that targeting class 1A PI3K may be a
      promising therapy for blocking tumor angiogenesis.

PMID- 18621723
TI  - Clues to the evolution of complex signaling machinery.

PMID- 18621724
TI  - Solution structure of the U2 snRNP protein Rds3p reveals a knotted zinc-finger
      motif.
AB  - Rds3p, a component of the U2 snRNP subcomplex SF3b, is essential for pre-mRNA
      splicing and is extremely well conserved in all eukaryotic species. We report
      here the solution structure of Rds3p, which reveals an unusual knotted fold
      unrelated to previously known knotted proteins. Rds3p has a triangular shape with
      a GATA-like zinc finger at each vertex. Pairs of cysteines contributing to each
      finger are arranged nonsequentially in a permuted arrangement reminiscent of
      domain-swapping but which here involves segments of subdomains within a single
      chain. We suggest that the structure arose through a process of segment swapping
      after gene duplication. The fingers are connected through beta-strands and loops,
      forming an overall topology strongly resembling a "triquetra knot." The
      conservation and surface properties of Rds3p suggest that it functions as a
      platform for protein assembly within the multiprotein SF3b complex of U2 snRNP.
      The recombinant protein used for structure determination is biologically active,
      as it restores splicing activity in a yeast splicing extract depleted of native
      Rds3p.

PMID- 18621725
TI  - Electrostatic funneling of substrate in mitochondrial inner membrane carriers.
AB  - Exchange of ATP and ADP across mitochondrial membrane replenishes the cytoplasm
      with newly synthesized ATP and provides the mitochondria with the substrate ADP
      for oxidative phosphorylation. The sole means of this exchange is the
      mitochondrial ADP/ATP carrier (AAC), a membrane protein that is suggested to
      cycle between two conformationally distinct states, cytosolic-open (c-state) and
      matrix-open (m-state), thereby shuttling nucleotides across the inner
      mitochondrial membrane. However, the c-state is the only structurally resolved
      state, and the binding site of ADP remains elusive. Here, we present
      approximately 0.3 mus of all-atom MD simulations of the c-state revealing rapid,
      spontaneous binding of ADP to deeply positioned binding sites within the AAC
      lumen. To our knowledge, a complete ligand-binding event has heretofore not been
      described in full atomic detail in unbiased simulations. The identified ADP-bound
      state and additional simulations shed light on key structural elements and the
      initial steps involved in conversion to the m-state. Electrostatic analysis of
      trajectories reveals the presence of an unusually strong positive electrostatic
      potential in the lumen of AAC that appears to be the main driving force for the
      observed spontaneous binding of ADP. We provide evidence that the positive
      electrostatic potential is likely a common attribute among the entire family of
      mitochondrial carriers. In addition to playing a key role in substrate
      recruitment and translocation, the electropositivity of mitochondrial carriers
      might also be critical for their binding to the negatively charged environment of
      the inner mitochondrial membrane.

PMID- 18621726
TI  - Bioinformatic method for protein thermal stabilization by structural entropy
      optimization.
AB  - Engineering proteins for higher thermal stability is an important and difficult
      challenge. We describe a bioinformatic method incorporating sequence alignments
      to redesign proteins to be more stable through optimization of local structural
      entropy. Using this method, improved configurational entropy (ICE), we were able
      to design more stable variants of a mesophilic adenylate kinase with only the
      sequence information of one psychrophilic homologue. The redesigned proteins
      display considerable increases in their thermal stabilities while still retaining
      catalytic activity. ICE does not require a three-dimensional structure or a large
      number of homologous sequences, indicating a broad applicability of this method.
      Our results also highlight the importance of entropy in the stability of protein
      structures.

PMID- 18621727
TI  - Molecular basis for the thiol sensitivity of insulin-degrading enzyme.
AB  - Insulin-degrading enzyme (IDE) is a ubiquitous zinc-metalloprotease that
      hydrolyzes several pathophysiologically relevant peptides, including insulin and
      the amyloid beta-protein (Abeta). IDE is inhibited irreversibly by compounds that
      covalently modify cysteine residues, a mechanism that could be operative in the
      etiology of type 2 diabetes mellitus (DM2) or Alzheimer's disease (AD). However,
      despite prior investigation, the molecular basis underlying the sensitivity of
      IDE to thiol-alkylating agents has not been elucidated. To address this topic, we
      conducted a comprehensive mutational analysis of the 13 cysteine residues within
      IDE. Our analysis implicates C178, C812, and C819 as the principal residues
      conferring thiol sensitivity. The involvement of C812 and C819, residues quite
      distant from the catalytic zinc atom, provides functional evidence that the
      active site of IDE comprises two separate domains that are operational only in
      close apposition. Structural analysis and other evidence predict that alkylation
      of C812 and C819 disrupts substrate binding, whereas alkylation of C178
      interferes with the apposition of active-site domains and subtly repositions zinc
      binding residues. Unexpectedly, alkylation of C590 was found to activate
      hydrolysis of Abeta significantly, while having no effect on insulin,
      demonstrating that chemical modulation of IDE can be both bidirectional and
      highly substrate selective. Our findings resolve a long-standing riddle about the
      basic enzymology of IDE with important implications for the etiology of DM2 and
      AD. Moreover, this work uncovers key details about the mechanistic basis of the
      unusual substrate selectivity of IDE that may aid the development of
      pharmacological agents or IDE mutants with therapeutic value.

PMID- 18621728
TI  - Identifying a property of origins of DNA synthesis required to support plasmids
      stably in human cells.
AB  - The plasmid origin of replication, oriP, of Epstein-Barr Virus (EBV) was
      identified in an assay to detect autonomously replicating sequences (ARSs) in
      human cells. Raji ori, a second origin in EBV, functions in vivo but fails in
      long-term ARS assays. We examined the initiating element, DS, within oriP and
      Raji ori to resolve this paradox. DS, but not Raji ori, binds EBNA1; whereas both
      act as ARSs in short-term assays, with DS being more efficient, only DS can act
      as an ARS in long-term assays. Surprisingly, we found that DS supported the
      establishment of a plasmid with Raji ori in cis and that after deletion of DS,
      Raji ori could now act as an ARS in the long term. This finding explains the
      frequent failure of ARS assays in mammalian cells. More origins can initially act
      as ARSs than can be established. We identified one requirement for ARSs to be
      established: They must function efficiently enough initially to generate a wide
      distribution of numbers of plasmids per cell. Only the cells that have more than
      a threshold number of plasmids can survive selections imposed on the cells to
      retain these replicons.

PMID- 18621730
TI  - Introduction of a lethal redox switch that controls the opening and closing of
      the hydrophobic cavity in LolA.
AB  - LolA plays a critical role in the outer membrane sorting of Escherichia coli
      lipoproteins because it carries a hydrophobic lipoprotein from the inner membrane
      through the hydrophilic periplasm to the outer membrane receptor LolB. LolA has
      an incomplete beta-barrel structure composed of 11 beta-strands with an alpha
      helical lid forming a hydrophobic cavity inside. The accompanying study revealed
      that the hydrophobic cavity opens and closes upon the binding and release of
      lipoproteins, respectively. Ile(93) in the alpha-helix and Phe(140) in the beta
      strand are located close to each other in the hydrophobic cavity. These two
      residues were replaced by Cys to construct the I93C/F140C derivative. Expression
      of I93C/F140C immediately arrested growth whether wild-type LolA was present or
      not. However, this dominant negative phenotype was abolished by reducing agents,
      indicating that the intramolecular disulfide bonding between the two Cys residues
      is lethal. I93C/F140C was unstable, and its periplasmic level was lower than that
      of wild-type LolA or its single Cys derivative. Reduction of I93C/F140C was
      essential for the release of lipoproteins from the inner membrane. Moreover,
      treatment of I93C/F140C with divalent cross-linkers having different side chain
      lengths revealed that opening of the lid for a sufficient distance is required
      for the release activity. The binding of a fluorescent probe to the hydrophobic
      cavity of I93C/F140C also depended on reducing agents. Taken together, these
      results indicate that the two Cys residues introduced into LolA function as a
      redox switch, which regulates the opening and closing of the hydrophobic cavity.

PMID- 18621729
TI  - The age lipid A2E and mitochondrial dysfunction synergistically impair
      phagocytosis by retinal pigment epithelial cells.
AB  - Accumulation of indigestible lipofuscin and decreased mitochondrial energy
      production are characteristic age-related changes of post-mitotic retinal pigment
      epithelial (RPE) cells in the human eye. To test whether these two forms of age
      related impairment have interdependent effects, we quantified the ATP-dependent
      phagocytic function of RPE cells loaded or not with the lipofuscin component A2E
      and inhibiting or not mitochondrial ATP synthesis either pharmacologically or
      genetically. We found that physiological levels of lysosomal A2E reduced
      mitochondrial membrane potential and inhibited oxidative phosphorylation (OXPHOS)
      of RPE cells. Furthermore, in media with physiological concentrations of glucose
      or pyruvate, A2E significantly inhibited phagocytosis. Antioxidants reversed
      these effects of A2E, suggesting that A2E damage is mediated by oxidative
      processes. Because mitochondrial mutations accumulate with aging, we generated
      novel genetic cellular models of RPE carrying mitochondrial DNA point mutations
      causing either moderate or severe mitochondrial dysfunction. Exploring these
      mutant RPE cells we found that, by itself, only the severe but not the moderate
      OXPHOS defect reduces phagocytosis. However, sub-toxic levels of lysosomal A2E
      are sufficient to reduce phagocytic activity of RPE with moderate OXPHOS defect
      and cause cell death of RPE with severe OXPHOS defect. Taken together, RPE cells
      rely on OXPHOS for phagocytosis when the carbon energy source is limited. Our
      results demonstrate that A2E accumulation exacerbates the effects of moderate
      mitochondrial dysfunction. They suggest that synergy of sub-toxic lysosomal and
      mitochondrial changes in RPE cells with age may cause RPE dysfunction that is
      known to contribute to human retinal diseases like age-related macular
      degeneration.

PMID- 18621731
TI  - Weak organic acids trigger conformational changes of the yeast transcription
      factor War1 in vivo to elicit stress adaptation.
AB  - The Saccharomyces cerevisiae zinc cluster regulator War1 mediates an essential
      transcriptional and adaptive response to weak organic acid stress. Here we
      investigate the mechanism of War1 activation upon weak acid stress. We identified
      several gain-of-function WAR1 alleles mapping to the central War1 region. These
      mutations constitutively increase levels of the plasma membrane ABC transporter
      Pdr12, the main War1 target mediating stress adaptation. Functional analysis of
      War1 reveals that the central region and its C-terminal activation domain are
      required for function. Notably, the native DNA-binding and dimerization domains
      appear dispensable for War1 activity, because they can be replaced by a LexA DNA
      binding domain. Chromatin immunoprecipitation demonstrates elevated promoter
      affinity of activated War1, because its PDR12 promoter association increases upon
      stress. Hyperactive WAR1 alleles have constitutively high PDR12 promoter
      association. Furthermore, fluorescence resonance energy transfer of functional
      CFP-War1-YFP proteins also demonstrates conformational changes of stress
      activated War1 in vivo. Our results suggest a mechanism whereby War1 activation
      is accompanied by conformational changes enhancing promoter association, thus
      initiating the adaptation process.

PMID- 18621732
TI  - Insights into small heat shock protein and substrate structure during chaperone
      action derived from hydrogen/deuterium exchange and mass spectrometry.
AB  - Small heat shock proteins (sHSPs) and the related alpha-crystallins are
      ubiquitous chaperones linked to neurodegenerative diseases, myopathies, and
      cataract. To better define their mechanism of chaperone action, we used
      hydrogen/deuterium exchange and mass spectrometry (HXMS) to monitor
      conformational changes during complex formation between the structurally defined
      sHSPs, pea PsHsp18.1, and wheat TaHsp16.9, and the heat-denatured model
      substrates malate dehydrogenase (MDH) and firefly luciferase. Remarkably, we
      found that even when complexed with substrate, the highly dynamic local structure
      of the sHSPs, especially in the N-terminal arm (>70% exchange in 5 s), remains
      unchanged. These results, coupled with sHSP-substrate complex stability, indicate
      that sHSPs do not adopt new secondary structure when binding substrate and
      suggest sHSPs are tethered to substrate at multiple sites that are locally
      dynamic, a feature that likely facilitates recognition and refolding of sHSP
      bound substrate by the Hsp70/DnaK chaperone system. Both substrates were found to
      be stabilized in a partially unfolded state that is observed only in the presence
      of sHSP. Furthermore, peptide-level HXMS showed MDH was substantially protected
      in two core regions (residues 95-156 and 228-252), which overlap with the MDH
      structure protected in the GroEL-bound MDH refolding intermediate. Significantly,
      despite differences in the size and structure of TaHsp16.9-MDH and PsHsp18.1-MDH
      complexes, peptide-level HXMS patterns for MDH in both complexes are virtually
      identical, indicating that stabilized MDH thermal unfolding intermediates are not
      determined by the identity of the sHSP.

PMID- 18621733
TI  - Differential roles of phosphatidylserine, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 in
      plasma membrane targeting of C2 domains. Molecular dynamics simulation, membrane
      binding, and cell translocation studies of the PKCalpha C2 domain.
AB  - Many cytosolic proteins are recruited to the plasma membrane (PM) during cell
      signaling and other cellular processes. Recent reports have indicated that
      phosphatidylserine (PS), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)),
      and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) that are present
      in the PM play important roles for their specific PM recruitment. To
      systematically analyze how these lipids mediate PM targeting of cellular
      proteins, we performed biophysical, computational, and cell studies of the Ca(2+)
      dependent C2 domain of protein kinase Calpha (PKCalpha) that is known to bind PS
      and phosphoinositides. In vitro membrane binding measurements by surface plasmon
      resonance analysis show that PKCalpha-C2 nonspecifically binds phosphoinositides,
      including PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3), but that PS and Ca(2+) binding
      is prerequisite for productive phosphoinositide binding. PtdIns(4,5)P(2) or
      PtdIns(3,4,5)P(3) augments the Ca(2+)- and PS-dependent membrane binding of
      PKCalpha-C2 by slowing its membrane dissociation. Molecular dynamics simulations
      also support that Ca(2+)-dependent PS binding is essential for membrane
      interactions of PKCalpha-C2. PtdIns(4,5)P(2) alone cannot drive the membrane
      attachment of the domain but further stabilizes the Ca(2+)- and PS-dependent
      membrane binding. When the fluorescence protein-tagged PKCalpha-C2 was expressed
      in NIH-3T3 cells, mutations of phosphoinositide-binding residues or depletion of
      PtdIns(4,5)P(2) and/or PtdIns(3,4,5)P(3) from PM did not significantly affect the
      PM association of the domain but accelerated its dissociation from PM. Also,
      local synthesis of PtdIns(4,5)P(2) or PtdIns(3,4,5)P(3) at the PM slowed membrane
      dissociation of PKCalpha-C2. Collectively, these studies show that
      PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3) augment the Ca(2+)- and PS-dependent
      membrane binding of PKCalpha-C2 by elongating the membrane residence of the
      domain but cannot drive the PM recruitment of PKCalpha-C2. These studies also
      suggest that effective PM recruitment of many cellular proteins may require
      synergistic actions of PS and phosphoinositides.

PMID- 18621734
TI  - The Haemophilus influenzae HMW1 adhesin is a glycoprotein with an unusual N
      linked carbohydrate modification.
AB  - The Haemophilus influenzae HMW1 adhesin mediates adherence to respiratory
      epithelial cells, a critical early step in the pathogenesis of H. influenzae
      disease. In recent work, we demonstrated that HMW1 undergoes glycosylation. In
      addition, we observed that glycosylation of HMW1 is essential for HMW1 tethering
      to the bacterial surface, a prerequisite for HMW1-mediated adherence to host
      epithelium. In this study, we examined HMW1 proteolytic fragments by mass
      spectrometry, achieved 89% amino acid sequence coverage, and identified 31 novel
      modification sites. All of the modified sites were asparagine residues, in all
      but one case in the conventional consensus sequence of N-linked glycans, viz.
      NX(S/T). Liquid chromatography-tandem mass spectrometry analysis using a hybrid
      linear quadrupole ion trap Fourier transform ion cyclotron mass spectrometer,
      accurate mass measurements, and deuterium exchange studies established that the
      modifying glycan structures were mono- or dihexoses rather than the N-acetylated
      chitobiosyl core that is characteristic of N-glycosylation. This unusual
      carbohydrate modification suggests that HMW1 glycosylation requires a
      glycosyltransferase with a novel activity.

PMID- 18621735
TI  - A conformationally mobile cysteine residue (Cys-561) modulates Na+ and H+
      activation of human CNT3.
AB  - In humans, the SLC28 concentrative nucleoside transporter (CNT) protein family is
      represented by three Na+-coupled members; human CNT1 (hCNT1) and hCNT2 are
      pyrimidine and purine nucleoside-selective, respectively, whereas hCNT3
      transports both purine and pyrimidine nucleosides and nucleoside drugs. Belonging
      to a phylogenetic CNT subfamily distinct from hCNT1/2, hCNT3 also mediates
      H+/nucleoside cotransport. Using heterologous expression in Xenopus oocytes, we
      have characterized a cysteineless version of hCNT3 (hCNT3C-). Processed normally
      to the cell surface, hCNT3C- exhibited hCNT3-like transport properties, but
      displayed a decrease in apparent affinity specific for Na+ and not H+. Site
      directed mutagenesis experiments in wild-type and hCNT3C- backgrounds identified
      intramembranous Cys-561 as the residue responsible for this altered Na+-binding
      phenotype. Alanine at this position restored Na+ binding affinity, whereas
      substitution with larger neutral amino acids (threonine, valine, and isoleucine)
      abolished hCNT3 H+-dependent nucleoside transport activity. Independent of these
      findings, we have established that Cys-561 is located in a mobile region of the
      hCNT3 translocation pore adjacent to the nucleoside binding pocket and that
      access of p-chloromercuribenzene sulfonate to this residue reports a specific H+
      induced conformational state of the protein ( Slugoski, M. D., Ng, A. M. L., Yao,
      S. Y. M., Smith, K. M., Lin, C. C., Zhang, J., Karpinski, E., Cass, C. E.,
      Baldwin, S. A., and Young, J. D. (2008) J. Biol. Chem. 283, 8496-8507 ). The
      present investigation validates hCNT3C- as a template for substituted cysteine
      accessibility method studies of CNTs and reveals a pivotal functional role for
      Cys-561 in Na+- as well as H+-coupled modes of hCNT3 nucleoside transport.

PMID- 18621736
TI  - RACK1, a new ADAM12 interacting protein. Contribution to liver fibrogenesis.
AB  - ADAM12 belongs to a disintegrin-like and metalloproteinase-containing protein
      family that possesses multidomain structures composed of a pro-domain, a
      metalloprotease, disintegrin-like, cysteine-rich, epidermal growth factor-like,
      and transmembrane domains, and a cytoplasmic tail. Overexpression of several
      ADAMs has been reported in human cancer, and we recently described the
      involvement of ADAM12 in liver injury (Le Pabic, H., Bonnier, D., Wewer, U. M.,
      Coutand, A., Musso, O., Baffet, G., Clement, B., and Theret, N. (2003) Hepatology
      37, 1056-1066). In this study, we used a yeast two-hybrid screening of a cDNA
      library from human hepatocellular carcinoma to analyze binding partners of
      ADAM12. We identify RACK1, a receptor for activated protein kinase C (PKC), as a
      new ADAM12 interacting protein. RACK1 is up-regulated in patients with
      hepatocellular carcinoma and is highly expressed by activated hepatic stellate
      cells. We demonstrate the involvement of RACK1 in mediating the PKC-dependent
      translocation of ADAM12 to membranes of activated hepatic stellate cells. In
      particular, treatment of cells with phorbol esters enhances ADAM12 immunostaining
      in the membrane fractions and the co-immunoprecipitation of ternary complexes
      containing RACK1, ADAM12, and PKC. By using RNA interference, we demonstrate that
      inhibition of RACK1 expression diminishes the phorbol 12-myristate 13-acetate
      dependent translocation of ADAM12 to membranes of hepatic stellate cells.
      Finally, hepatic stellate cells cultured on coated type I collagen induces
      relocalization of ADAM12 in the membrane, suggesting that this major matrix
      component in liver cancer and fibrogenesis might stimulate ADAM12 translocation
      to the cell membrane where its shedding activity takes place.

PMID- 18621737
TI  - c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha
      (TNFalpha)-induced NF-kappaB activation.
AB  - The inhibitor of apoptosis (IAP) proteins are a family of anti-apoptotic
      regulators found in viruses and metazoans. c-IAP1 and c-IAP2 are recruited to
      tumor necrosis factor receptor 1 (TNFR1)-associated complexes where they can
      regulate receptor-mediated signaling. Both c-IAP1 and c-IAP2 have been implicated
      in TNFalpha-stimulated NF-kappaB activation. However, individual c-IAP1 and c
      IAP2 gene knock-outs in mice did not reveal changes in TNF signaling pathways,
      and the phenotype of a combined deficiency of c-IAPs has yet to be reported. Here
      we investigate the role of c-IAP1 and c-IAP2 in TNFalpha-stimulated activation of
      NF-kappaB. We demonstrate that TNFalpha-induced NF-kappaB activation is severely
      diminished in the absence of both c-IAP proteins. In addition, combined absence
      of c-IAP1 and c-IAP2 rendered cells sensitive to TNFalpha-induced cell death.
      Using cells with genetic ablation of c-IAP1 or cells where the c-IAP proteins
      were eliminated using IAP antagonists, we show that TNFalpha-induced RIP1
      ubiquitination is abrogated in the absence of c-IAPs. Furthermore, we
      reconstitute the ubiquitination process with purified components in vitro and
      demonstrate that c-IAP1, in collaboration with the ubiquitin conjugating enzyme
      (E2) enzyme UbcH5a, mediates polymerization of Lys-63-linked chains on RIP1.
      Therefore, c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1
      ubiquitination and NF-kappaB activation.

PMID- 18621738
TI  - Design of a disulfide-less, pharmacologically inert, and chemically competent
      analog of maurocalcine for the efficient transport of impermeant compounds into
      cells.
AB  - Maurocalcine is a 33-mer peptide initially isolated from the venom of a Tunisian
      scorpion. It has proved itself valuable as a pharmacological activator of the
      ryanodine receptor and has helped the understanding of the molecular basis
      underlying excitation-contraction coupling in skeletal muscles. Because of its
      positively charged nature, it is also an innovative vector for the cell
      penetration of various compounds. We report a novel maurocalcine analog with
      improved properties: (i) the complete loss of pharmacological activity, (ii)
      preservation of the potent ability to carry cargo molecules into cells, and (iii)
      coupling chemistries not affected by the presence of internal cysteine residues
      of maurocalcine. We did this by replacing the six internal cysteine residues of
      maurocalcine by isosteric 2-aminobutyric acid residues and by adding an
      additional N-terminal biotinylated lysine (for a proof of concept analog) or an N
      terminal cysteine residue (for a chemically competent coupling analogue).
      Additional replacement of a glutamate residue by alanyl at position 12 further
      improves the potency of these analogues. Coupling to several cargo molecules or
      nanoparticles are presented to illustrate the cell penetration potency and
      usefulness of these pharmacologically inactive analogs.

PMID- 18621739
TI  - Acetylation of PML is involved in histone deacetylase inhibitor-mediated
      apoptosis.
AB  - PML is a potent tumor suppressor and proapoptotic factor and is functionally
      regulated by post-translational modifications such as phosphorylation,
      sumoylation, and ubiquitination. Histone deacetylase (HDAC) inhibitors are a
      promising class of targeted anticancer agents and induce apoptosis in cancer
      cells by largely unknown mechanisms. We report here a novel post-transcriptional
      modification, acetylation, of PML. PML exists as an acetylated protein in HeLa
      cells, and its acetylation is enhanced by coexpression of p300 or treatment with
      a HDAC inhibitor, trichostatin A. Increased PML acetylation is associated with
      increased sumoylation of PML in vitro and in vivo. PML is involved in
      trichostatin A-induced apoptosis and PML with an acetylation-defective mutation
      shows an inability to mediate apoptosis, suggesting the importance of PML
      acetylation. Our work provides new insights into PML regulation by post
      translational modification and new information about the therapeutic mechanism of
      HDAC inhibitors.

PMID- 18621741
TI  - Stopping a trial early in oncology: for patients or for industry?

PMID- 18621740
TI  - Switching of G-protein usage by the calcium-sensing receptor reverses its effect
      on parathyroid hormone-related protein secretion in normal versus malignant
      breast cells.
AB  - The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that signals
      in response to extracellular calcium and regulates parathyroid hormone secretion.
      The CaR is also expressed on normal mammary epithelial cells (MMECs), where it
      has been shown to inhibit secretion of parathyroid hormone-related protein
      (PTHrP) and participate in the regulation of calcium and bone metabolism during
      lactation. In contrast to normal breast cells, the CaR has been reported to
      stimulate PTHrP production by breast cancer cells. In this study, we confirmed
      that the CaR inhibits PTHrP production by MMECs but stimulates PTHrP production
      by Comma-D cells (immortalized murine mammary cells) and MCF-7 human breast
      cancer cells. We found that changes in intracellular cAMP, but not phospholipase
      C or MAPK signaling, correlated with the opposing effects of the CaR on PTHrP
      production. Pharmacologic stimulation of cAMP accumulation increased PTHrP
      production by normal and transformed breast cells. Inhibition of protein kinase A
      activity mimicked the effects of CaR activation on inhibiting PTHrP secretion by
      MMECs and blocked the effects of the CaR on stimulating PTHrP production in Comma
      D and MCF-7 cells. We found that the CaR coupled to Galphai in MMECs but coupled
      to Galphas in Comma-D and MCF-7 cells. Thus, the opposing effects of the CaR on
      PTHrP production are because of alternate G-protein coupling of the receptor in
      normal versus transformed breast cells. Because PTHrP contributes to
      hypercalcemia and bone metastases, switching of G-protein usage by the CaR may
      contribute to the pathogenesis of breast cancer.

PMID- 18621742
TI  - Stoffenmanager exposure model: development of a quantitative algorithm.
AB  - In The Netherlands, the web-based tool called 'Stoffenmanager' was initially
      developed to assist small- and medium-sized enterprises to prioritize and control
      risks of handling chemical products in their workplaces. The aim of the present
      study was to explore the accuracy of the Stoffenmanager exposure algorithm. This
      was done by comparing its semi-quantitative exposure rankings for specific
      substances with exposure measurements collected from several occupational
      settings to derive a quantitative exposure algorithm. Exposure data were
      collected using two strategies. First, we conducted seven surveys specifically
      for validation of the Stoffenmanager. Second, existing occupational exposure data
      sets were collected from various sources. This resulted in 378 and 320
      measurements for solid and liquid scenarios, respectively. The Spearman
      correlation coefficients between Stoffenmanager scores and exposure measurements
      appeared to be good for handling solids (r(s) = 0.80, N = 378, P < 0.0001) and
      liquid scenarios (r(s) = 0.83, N = 320, P < 0.0001). However, the correlation for
      liquid scenarios appeared to be lower when calculated separately for sets of
      volatile substances with a vapour pressure >10 Pa (r(s) = 0.56, N = 104, P <
      0.0001) and non-volatile substances with a vapour pressure < or =10 Pa (r(s) =
      0.53, N = 216, P < 0.0001). The mixed-effect regression models with natural log
      transformed Stoffenmanager scores as independent parameter explained a
      substantial part of the total exposure variability (52% for solid scenarios and
      76% for liquid scenarios). Notwithstanding the good correlation, the data show
      substantial variability in exposure measurements given a certain Stoffenmanager
      score. The overall performance increases our confidence in the use of the
      Stoffenmanager as a generic tool for risk assessment. The mixed-effect regression
      models presented in this paper may be used for assessment of so-called reasonable
      worst case exposures. This evaluation is considered as an ongoing process and
      when more good quality data become available, the analyses described in this
      paper will be expanded. Based on these analyses, the algorithm will be refined in
      the near future.

PMID- 18621743
TI  - Comorbid forms of psychopathology: key patterns and future research directions.
AB  - The purpose of this review is to systematically appraise the peer-reviewed
      literature about clustered forms of psychopathology and to present a framework
      that can be useful for studying comorbid psychiatric disorders. The review
      focuses on four of the most prevalent types of mental health problems: anxiety,
      depression, conduct disorder, and substance abuse. The authors summarize existing
      empirical research on the distribution of concurrent and sequential comorbidity
      in children and adolescents and in adults, and they review existing knowledge
      about exogenous risk factors that influence comorbidity. The authors include
      articles that used a longitudinal study design and used psychiatric definitions
      of the disorders. A total of 58 articles met the inclusion criteria and were
      assessed. Current evidence demonstrates a reciprocal, sequential relation between
      most comorbid pairs, although the mechanisms that mediate such links remain to be
      explained. Methodological concerns include the inconsistency of measurement of
      the disorders across studies, small sample sizes, and restricted follow-up times.
      Given the significant mental health burden placed by comorbid disorders, and
      their high prevalence across populations, research on the key risk factors for
      clustering of psychopathology is needed.

PMID- 18621744
TI  - Impaired tyrosine phosphorylation of membrane type 1-matrix metalloproteinase
      reduces tumor cell proliferation in three-dimensional matrices and abrogates
      tumor growth in mice.
AB  - Pericellular proteolysis of the extracellular matrix by membrane type 1-matrix
      metalloproteinase (MT1-MMP) confers tumor cells with the ability to proliferate
      within three-dimensional (3D) matrices and sustains tumor growth in mice. In this
      study, we show that in addition to its matrix-degrading activity, phosphorylation
      of MT1-MMP on its unique tyrosine residue located within its cytoplasmic sequence
      (Tyr573) may also participate to these processes. Fibrosarcoma cells expressing a
      proteolytically active but non-phosphorylable mutant of MT1-MMP showed a markedly
      reduced proliferation rate when embedded within 3D type I collagen matrices, this
      antiproliferative effect being correlated with arrest in the G(0)/G(1) phase of
      the cell cycle. Impaired tyrosine phosphorylation of MT1-MMP also inhibits
      anchorage-independent growth of HT-1080 cells in soft agar as well as their
      invasion of collagen barriers, two prominent attributes of tumor cells,
      suggesting a broad inhibitory effect of the MT1-MMP mutant on tumorigenesis.
      Accordingly, whereas HT-1080 cells formed well-vascularized tumors containing
      tyrosine-phosphorylated MT1-MMP, tumor growth was completely abolished by
      expression of the non-phosphorylable MT1-MMP mutant. These findings thus indicate
      a close co-operation between the matrix-degrading activity of MT1-MMP and
      tyrosine phosphorylation of its intracellular domain for tumor cell invasion and
      proliferation and suggest that the targeting of the intracellular signaling
      pathways leading to tyrosine phosphorylation of MT1-MMP may represent an
      unexpected alternative strategy for the inhibition of this enzyme.

PMID- 18621745
TI  - SNAREing the basis of multicellularity: consequences of protein family expansion
      during evolution.
AB  - Vesicle trafficking between intracellular compartments of eukaryotic cells is
      mediated by conserved protein machineries. In each trafficking step, fusion of
      the vesicle with the acceptor membrane is driven by a set of distinctive soluble
      N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins
      that assemble into tight 4-helix bundle complexes between the fusing membranes.
      During evolution, about 20 primordial SNARE types were modified independently in
      different eukaryotic lineages by episodes of duplication and diversification.
      Here we show that 2 major changes in the SNARE repertoire occurred in the
      evolution of animals, each reflecting a main overhaul of the endomembrane system.
      In addition, we found several lineage-specific losses of distinct SNAREs,
      particularly in nematodes and platyhelminthes. The first major transformation
      took place during the transition to multicellularity. The primary event that
      occurred during this transformation was an increase in the numbers of endosomal
      SNAREs, but the SNARE-related factor lethal giant larvae also emerged.
      Apparently, enhanced endosomal sorting capabilities were an advantage for early
      multicellular animals. The second major transformation during the rise of
      vertebrates resulted in a robust expansion of the secretory set of SNAREs, which
      may have helped develop a more versatile secretory apparatus.

PMID- 18621747
TI  - Detecting short tandem repeats from genome data: opening the software black box.
AB  - Short tandem repeats, specifically microsatellites, are widely used genetic
      markers, associated with human genetic diseases, and play an important role in
      various regulatory mechanisms and evolution. Despite their importance, much is
      yet unknown about their mutational dynamics. The increasing availability of
      genome data has led to several in silico studies of microsatellite evolution
      which have produced a vast range of algorithms and software for tandem repeat
      detection. Documentation of these tools is often sparse, or provided in a format
      that is impenetrable to most biologists without informatics background. This
      article introduces the major concepts behind repeat detecting software essential
      for informed tool selection. We reflect on issues such as parameter settings and
      program bias, as well as redundancy filtering and efficiency using examples from
      the currently available range of programs, to provide an integrated comparison
      and practical guide to microsatellite detecting programs.

PMID- 18621746
TI  - The orl rat with inherited cryptorchidism has increased susceptibility to the
      testicular effects of in utero dibutyl phthalate exposure.
AB  - Phenotype results from interactions between genetics and environment, but for
      most environmental chemical exposures, such interactions are theoretical. The
      phenotypic response of the testis to in utero dibutyl phthalate (DBP) exposure
      was compared between two strains of Long-Evans (LE) rats, the orl substrain with
      inherited cryptorchidism and an outbred (wt) strain. orl and wt LE rats were
      exposed daily between gestational day (GD) 12 and GD21 to DBP dose levels ranging
      from 50 to 200 mg/kg by oral gavage and sensitive phthalate testicular end points
      examined at either GD19, GD21, or postnatal day (PND) 21. At 50 mg/kg DBP, GD19
      expression of Cyp17a1, Insl3, and Scarb1 was significantly reduced in orl but not
      wt testis. At GD21, statistically significant differential strain effects (orl
      more sensitive than wt) were observed for testicular expression of Scarb1 at 50
      and 200 mg/kg DBP and Star at 200 mg/kg DBP. Similarly, DBP exposure
      disproportionately increased GD21 seminiferous cord diameters and numbers of
      multinucleated germ cells in the orl strain. At PND21, body weight-corrected
      testis weights were lowered significantly by DBP exposure at all dose levels in
      the orl strain but not in wt rats. While the frequency of undescended testes
      after 200 mg/kg DBP exposure in the orl strain appeared increased, these data
      were not statistically significant. These results demonstrated enhanced
      sensitivity of the orl rat to phthalate exposure as compared to its parent
      strain, a potentially important model of the effects of gene-environment
      interaction on development of male reproductive malformations.

PMID- 18621748
TI  - Experience using web services for biological sequence analysis.
AB  - Programmatic access to data and tools through the web using so-called web
      services has an important role to play in bioinformatics. In this article, we
      discuss the most popular approaches based on SOAP/WS-I and REST and describe our,
      a cross section of the community, experiences with providing and using web
      services in the context of biological sequence analysis. We briefly review main
      technological approaches as well as best practice hints that are useful for both
      users and developers. Finally, syntactic and semantic data integration issues
      with multiple web services are discussed.

PMID- 18621749
TI  - The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process
      in osteoarthritic chondrocytes.
AB  - OBJECTIVES: Previous work has shown that the CO-releasing molecule CORM-2
      protects against cartilage degradation. The aim of this study was to examine
      whether CORM-2 can control the production of inflammatory mediators in
      osteoarthritic chondrocytes and determine the mechanisms involved. METHODS:
      Primary cultures of chondrocytes from OA patients were stimulated with IL-1beta.
      The production of reactive oxygen species, nitrite, PGE(2), TNF-alpha and IL-1
      receptor antagonist (IL-1Ra) were measured in the presence or absence of CORM-2.
      The expression of nitric oxide synthase-2 (NOS-2), cyclo-oxygenase-2 (COX-2) and
      microsomal PG E synthase-1 (mPGES-1) was followed by western blot and real-time
      PCR. Activation of nuclear factor-kappaB (NF-kappaB) and hypoxia inducible factor
      1alpha (HIF-1alpha), and phosphorylation of NF-kappaB inhibitory protein alpha
      (IkappaBalpha) were determined by ELISA. RESULTS: CORM-2 decreased the production
      of oxidative stress, nitrite and PGE(2). In addition, CORM-2 inhibited IL-1beta
      induced TNF-alpha but enhanced IL-1Ra production. Treatment of chondrocytes with
      CORM-2 strongly down-regulated NOS-2 and mPGES-1 protein expression, whereas COX
      2 was reduced to a lesser extent. These changes were accompanied by a significant
      decrease in mRNA expression for NOS-2 and mPGES-1. CORM-2 showed a concentration
      dependent inhibition of DNA-binding activity for p65 NF-kappaB and HIF-1alpha.
      IkappaBalpha phosphorylation was also reduced by CORM-2 treatment. CONCLUSIONS:
      These data have opened new mechanisms of action for CORM-2, raising the prospect
      that CO-releasing molecules are an interesting strategy for the development of
      new treatments in articular conditions.

PMID- 18621750
TI  - Clinical outcome in children with chronic recurrent multifocal osteomyelitis.
AB  - OBJECTIVE: To determine the clinical outcome of children with chronic recurrent
      multifocal osteomyelitis (CRMO). METHODS: We retrospectively reviewed clinical,
      biological and radiological data of children with CRMO at five French paediatric
      centres. Outcome data were obtained through review of hospital charts and
      questionnaires sent to all patients to assess disease activity and educational
      and vocational achievement. RESULTS: Forty patients were assessed (34 females and
      6 males) with a median age at diagnosis of 11.5 yrs (range 2-17). Median number
      of initial bony lesions was 2 at onset, and 3.5 over disease course. Median time
      since diagnosis was 3.5 yrs (range 0.5-15) and median duration of active disease
      2.7 yrs (range 0.5-13.5). Nine (22.5%) patients had psychological or physical
      sequelae. Twenty-nine children (72.5%) responded to the questionnaire. Twenty-six
      had no physical disability as judged by the HAQ 0-1, two had moderate disability
      (HAQ: 1-2) and one had severe disability (HAQ: 2-3). Seventeen patients (58.6%)
      had active disease at follow-up (after 6 months to 15 yrs since diagnosis) and
      continued to have pain (median value of visual analogue scale: 10/100). CRMO had
      interfered with patient's education in two cases. CONCLUSIONS: Clinical outcome
      of children with CRMO is generally good, but a sizeable proportion of patients
      have active disease at follow-up, and a minority of patients can have a severe
      and prolonged disease course despite intensive treatments. Further studies are
      required to determine predictive factors for severe disease.

PMID- 18621751
TI  - Signalling, inflammation and arthritis: Crossed signals: the role of interleukin
      15 and -18 in autoimmunity.
AB  - Several cytokines are involved in the complex processes ultimately leading to
      autoimmune diseases. In a preceding review, we have already discussed the role of
      the IL-12 and -17 families of cytokines. This review is focused on IL-15 and -18.
      Both these molecules have pro-inflammatory activity and act on many cell types
      and because of their broad spectrum of activity they play an important role in
      autoimmunity and disease pathogenesis. Their biological activity is ultimately
      regulated by the signalling cascades set into motion within their target cells.
      In this second review, we will, once again, describe the signal transduction
      pathways activated by these two cytokines and focus on how this relates to the
      pathogenesis of autoimmune diseases. We will also describe some of the
      therapeutic approaches that are being investigated to curtail the pro
      inflammatory activities of these two molecules.

PMID- 18621752
TI  - The sperm chemoattractant secreted from human cumulus cells is progesterone.
AB  - BACKGROUND: Human spermatozoa appear to be guided by chemotaxis to the oocyte in
      the female genital tract. While one of the sources of sperm chemoattractants is
      the cumulus cells that surround the oocyte, the identity of the chemoattractant
      secreted from them is unknown. Progesterone, recognized to be secreted from
      cumulus cells, was demonstrated, at the pM concentration range, to be a
      chemoattractant for human spermatozoa. Here, we examined whether this steroid is
      the cumulus-originated chemoattractant for human spermatozoa. METHODS: Human
      cumulus cells were cultured, and the cultured medium was demonstrated to be
      chemotactically active. Progesterone was then eliminated from the medium by a
      specific anti-progesterone antibody, and the residual chemotactic activity was
      assessed. RESULTS: The rate of progesterone secretion from the cells decreased
      with time. Removal of progesterone from the cumulus-cultured medium resulted in
      total loss of the chemotactic activity of the medium. Furthermore, the cumulus
      cultured medium could substitute for progesterone in stimulating changes in the
      intracellular Ca(2+) concentration in the spermatozoa, and the changes were very
      similar to those caused by measured progesterone concentrations in the medium.
      CONCLUSIONS: Taken together, the results suggest that progesterone is the main,
      if not the sole, chemoattractant secreted by human cumulus cells.

PMID- 18621753
TI  - Regulation of muscular contractions in the human Fallopian tube through
      prostaglandins and progestagens.
AB  - BACKGROUND: Transport of gametes and embryos is an important function of the
      Fallopian tube. Both muscular contractions and cilia activity are involved in the
      transportation. Prostaglandins (PGs) are known mediators of muscular
      contractility. PG receptors have previously been demonstrated in the human
      Fallopian tube. The aim was to study the effect of PGs and progestagens,
      antiprogestin, hCG and oxytocin on muscular contractions in the human Fallopian
      tube, and the hormonal regulation of PG receptors. METHODS: Twenty-two healthy
      women operated for benign causes were included in the study. The ampullary
      isthmic junction of the Fallopian tubes was excised and used for in vitro
      contractility studies. The effect of PGE(1), PGE(2), PGF(2alpha), progesterone,
      mifepristone, levonorgestrel, oxytocin and hCG on contractility was studied.
      Explants of Fallopian tubes were cultured for 24 h to study the effect of
      progestagens and hCG on the expression of PG receptors using immunohistochemistry
      and real-time PCR. RESULTS: Muscular contractions increased after treatment with
      PGF(2alpha) and PGE(2) (P < 0.05). The contractions decreased after PGE(1),
      progesterone, levonorgestrel, mifepristone, oxytocin and hCG (P < 0.05). In tubal
      explant studies, relative mRNA expression of EP1, EP2, EP3 and FP increased after
      levonorgestrel treatment (P < 0.05). Mifepristone and levonorgestrel treatment
      increased immunostaining intensity of EP1 and EP2 protein, in lumen, muscle and
      vessels. Progesterone and mifepristone increased immunostaining of FP in vessels.
      CONCLUSIONS: These data suggest that the transport of gametes and embryos
      involves the action of PGs, progesterone, oxytocin and hCG on muscular
      contractility.

PMID- 18621754
TI  - Trophoblastic invasion in vitro and in vivo: similarities and differences.
AB  - BACKGROUND: The basic mechanisms of trophoblast invasion are not completely
      understood. This may be due to the lack of suitable in vitro models which enable
      experimental modulation of this complex process. In the present study, a three
      dimensional co-culture model is used for comparing two factors considered to be
      implicated in the regulation of trophoblast invasion, the expression of HLA-G and
      apoptosis, in vitro and in vivo. METHODS: Tissue fragments from human first
      trimester decidua parietalis were put in close contact with spheroids of AC-1M59
      trophoblast/choriocarcinoma hybrid cells as a model of the invasive trophoblast.
      Cryostat sections from these co-cultures were immunohistochemically stained and
      compared with first trimester placentation sites in vivo. RESULTS: Only the
      invasive trophoblast-derived cells showed an intensive staining for HLA-G,
      whereas the cells on the periphery of the confrontation culture exhibited only a
      weak staining. A similar staining pattern was found in vivo. Both in vitro and in
      vivo CD45(+) apoptotic leukocytes were frequently detected in close proximity to
      the invasive trophoblastic cells. CONCLUSIONS: In this co-culture system, key
      factors considered to be implicated in trophoblast invasion in vivo can also be
      demonstrated in vitro. Therefore, it may help in finding strategies for the
      management of diseases associated with deficient trophoblast invasion.

PMID- 18621755
TI  - Chromosomal aneuploidy in embryos conceived with unstimulated cycle IVF.
AB  - There is an ever increasing trend in reproductive medicine to reduce the
      intensity of ovarian stimulation for in vitro fertilization (IVF) and to restrict
      the number of embryos that are transferred into the uterine cavity. Recent
      findings suggest that the magnitude of ovarian stimulation affects the proportion
      of euploid embryos. As a result of the restriction in the number of embryos
      transferred, it becomes even more important to select the embryo with optimum
      implantational and developmental potential. Our aim was to asses the prevalence
      of numerical chromosomal abnormalities (aneuploidy) in unstimulated cycle IVF
      embryos. Thirty patients (mean age 31.4 years) underwent oocyte retrieval in a
      natural cycle without any form of ovarian stimulation, followed by
      intracytoplasmic sperm injection and Preimplantation genetic aneuploidy screening
      (PGS) for chromosomes X, Y, 13, 16, 18, 21 and 22. Out of 30 cycles, 21 oocytes
      were retrieved, 15 of which fertilized successfully. Eleven embryos developed
      sufficiently in order to undergo the PGS analysis, and four embryos proved to be
      aneuploid (36.4%; 95% CI: 10.9-69.2%). Six normal embryos were transferred in
      utero, resulting in three ongoing pregnancies. Two healthy girls were born and
      one patient miscarried. Numerical chromosomal abnormalities (aneuploidy) are
      present even in embryos of young women, and in the absence of ovarian
      stimulation.

PMID- 18621756
TI  - Glycan stem-cell markers are specifically expressed by spermatogonia in the adult
      non-human primate testis.
AB  - BACKGROUND: The glycan cell surface molecules, stage-specific embryonic antigen
      (SSEA)-1, -3 and -4 and tumor-rejection antigen (TRA)-1-60 and -1-81, are
      expressed in specific combinations by undifferentiated pluripotent cells, i.e.
      embryonic stem cells, induced pluripotent stem cells, embryonal carcinoma cells,
      primordial germ cells and embryonic germ cells. Upon differentiation of the
      cells, these markers vanish. Recently, it has been shown that also neonatal and
      adult mouse testes contain pluripotent cells. Here, we aimed at identifying in
      situ possibly pluripotent cells in the adult primate testis. METHODS: Monoclonal
      antibodies raised against the glyco-epitopes SSEA-1, -3 and -4 and TRA-1-60 and 
      1-81, respectively, were tested to detect cells expressing the antigens, by
      immunohistochemistry on Bouin's-fixed and paraffin-embedded adult primate testes.
      Man, the new-world monkey, Callithrix jacchus (common marmoset), and the old
      world monkey species, Macaca mulatta (Rhesus macaque) and Macaca silenus (Lion
      tailed macaque), were included. The percentage of SSEA-4-positive cells in three
      adult marmoset testes was determined using flow cytometry. RESULTS: Spermatogonia
      in the testes of C. jacchus were labeled by SSEA-4, TRA-1-60 and -1-81
      antibodies. In the macaques, spermatogonia were detected by SSEA-4 and TRA-1-81
      antibodies. TRA-1-61 did not bind to macaque spermatogonia. Also, SSEA-1 and -3
      did not bind to spermatogonia in any species. In human testes, we never obtained
      any clear staining. The total percentage of SSEA-4-positive cells in marmoset
      testes was 8.6 +/- 1.61%. CONCLUSIONS: SSEA-4 and TRA-1-81-antibodies may be very
      well suited for the identification and isolation of spermatogonia, and possibly
      also germline stem cells, in the non-human primate testis.

PMID- 18621757
TI  - Integrating metabolic, transcriptional regulatory and signal transduction models
      in Escherichia coli.
AB  - MOTIVATION: The effort to build a whole-cell model requires the development of
      new modeling approaches, and in particular, the integration of models for
      different types of processes, each of which may be best described using different
      representation. Flux-balance analysis (FBA) has been useful for large-scale
      analysis of metabolic networks, and methods have been developed to incorporate
      transcriptional regulation (regulatory FBA, or rFBA). Of current interest is the
      integration of these approaches with detailed models based on ordinary
      differential equations (ODEs). RESULTS: We developed an approach to modeling the
      dynamic behavior of metabolic, regulatory and signaling networks by combining FBA
      with regulatory Boolean logic, and ordinary differential equations. We use this
      approach (called integrated FBA, or iFBA) to create an integrated model of
      Escherichia coli which combines a flux-balance-based, central carbon metabolic
      and transcriptional regulatory model with an ODE-based, detailed model of
      carbohydrate uptake control. We compare the predicted Escherichia coli wild-type
      and single gene perturbation phenotypes for diauxic growth on glucose/lactose and
      glucose/glucose-6-phosphate with that of the individual models. We find that iFBA
      encapsulates the dynamics of three internal metabolites and three transporters
      inadequately predicted by rFBA. Furthermore, we find that iFBA predicts different
      and more accurate phenotypes than the ODE model for 85 of 334 single gene
      perturbation simulations, as well for the wild-type simulations. We conclude that
      iFBA is a significant improvement over the individual rFBA and ODE modeling
      paradigms. AVAILABILITY: All MATLAB files used in this study are available at
      http://www.simtk.org/home/ifba/. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 18621758
TI  - Classification with reject option in gene expression data.
AB  - MOTIVATION: The classification methods typically used in bioinformatics classify
      all examples, even if the classification is ambiguous, for instance, when the
      example is close to the separating hyperplane in linear classification. For
      medical applications, it may be better to classify an example only when there is
      a sufficiently high degree of accuracy, rather than classify all examples with
      decent accuracy. Moreover, when all examples are classified, the classification
      rule has no control over the accuracy of the classifier; the algorithm just aims
      to produce a classifier with the smallest error rate possible. In our approach,
      we fix the accuracy of the classifier and thereby choose a desired risk of error.
      RESULTS: Our method consists of defining a rejection region in the feature space.
      This region contains the examples for which classification is ambiguous. These
      are rejected by the classifier. The accuracy of the classifier becomes a user
      defined parameter of the classification rule. The task of the classification rule
      is to minimize the rejection region with the constraint that the error rate of
      the classifier be bounded by the chosen target error. This approach is also used
      in the feature-selection step. The results computed on both synthetic and real
      data show that classifier accuracy is significantly improved. AVAILABILITY:
      Companion Website. http://gsp.tamu.edu/Publications/rejectoption/

PMID- 18621759
TI  - Are learning portfolios worth the effort? Yes.

PMID- 18621760
TI  - Are learning portfolios worth the effort? No.

PMID- 18621761
TI  - Patient consent for information sharing not always possible or appropriate.

PMID- 18621763
TI  - Standards for adult sickle cell disease aim to reduce gaps in care.

PMID- 18621762
TI  - Management of breast cancer--Part II.

PMID- 18621764
TI  - Rising age of starting family in Netherlands reflects fall in younger not rise in
      older mothers.

PMID- 18621765
TI  - Pharmacists rather than GPs should be first contact for minor ailments, report
      says.

PMID- 18621766
TI  - Characterization of an acrosome protein VAD1.2/AEP2 which is differentially
      expressed in spermatogenesis.
AB  - The release of enzymes from the acrosome of the sperm head (acrosome reaction)
      starts the fertilization process and enables the spermatozoa to penetrate the
      zona pellucida of the oocytes. Defective acrosome reaction is one of the
      important causes of infertility in men. To investigate the molecular regulation
      of spermatogenesis in vivo, we used differential display reverse transcription
      polymerase chain reaction to identify stage-specific genes in a retinol
      supplemented vitamin-A deficiency (VAD) rat model and identified the VAD1.2
      (acrosome-expressed protein 2, AEP2) gene, which was expressed strongly in the
      rat testis from post-natal day 32 to adult stage. The mouse VAD1.2 mRNA shared
      85% and 67% sequence homology, and 74% and 38% amino acid homology, respectively,
      with the rat and human counterparts. VAD1.2 transcript was abundantly expressed
      in the rat seminiferous tubules at stage VIII-XII, and the protein was detected
      in the acrosome region of the round and elongated spermatids of mouse, human,
      monkey and pig. VAD1.2 co-localized with lectin-PNA to the acrosome region of
      spermatids. Interestingly, the expression of VAD1.2 protein in human testis
      diminished in patients with hypospermatogenesis, maturation arrest, undescended
      testis and Sertoli cell-only syndrome. Co-immunoprecipitation experiments
      followed by western blotting and mass spectrometry (MS-MS) identified syntaxin 1,
      beta-actin and myosin heavy chain (MHC) proteins as putative interacting
      partners. Taken together, the stage-specific expression of VAD1.2 in the acrosome
      of spermatids and the binding of VAD1.2 protein with vesicle forming (syntaxin 1)
      and structural (beta-actin and MHC) proteins suggest that VAD1.2 maybe involved
      in acrosome formation during spermiogenesis.

PMID- 18621767
TI  - Effects of natural ligands of PPARgamma on lipid metabolism in placental tissues
      from healthy and diabetic rats.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      dependent nuclear receptor that plays an important role in placental development
      and function metabolism in diabetic and control rats after midpregnancy, as well
      as the concentrations of the PPARgamma endogenous agonist
      15deoxyDelta(12,14)Prostaglandin J(2) (15dPGJ(2)). In vitro experiments showed
      that 15dPGJ(2) did not regulate placental concentrations of triglycerides,
      cholesteryl esters, phospholipids and free fatty acids, but decreased the de novo
      synthesis of these lipid species. PPAR agonists were administered in vivo through
      dietary supplementation with either 6% olive oil or 6% safflower oil. These
      treatments led to increases in placental lipid mass in control tissues and more
      markedly in diabetic tissues. In addition, they led to reductions in the de novo
      lipid synthesis both in control and in diabetic placental tissues. In the
      placenta from diabetic rats fed with the standard diet, 15dPGJ(2) concentrations
      were greatly reduced. Both dietary supplementations increased the concentrations
      of 15dPGJ(2) in placentas from control and diabetic rats. These data indicate
      that, in the placenta, PPARgamma natural ligands regulate the concentration of
      their own endogenous ligands. In addition, they increase the placental capacity
      to accumulate maternal-derived lipids, and reduce the de novo lipid synthesis,
      thus regulating metabolic pathways that are altered in the placenta from diabetic
      rats and involved in the lipid transfer to the developing fetus.

PMID- 18621768
TI  - Successful catheter ablation of premature ventricular contractions originating
      from the tricuspid annulus using a Halo-type catheter.
AB  - A 31-year-old woman with idiopathic premature ventricular contractions
      originating from the tricuspid annulus (TA) underwent electrophysiological
      testing. Activation mapping with a 20-pole bipolar Halo-type catheter positioned
      along the TA revealed the earliest ventricular activation at a site between 7 and
      8 o'clock along the TA. A reversal in the polarity of the local ventricular
      electrograms was observed between the two neighbouring electrode pairs of the TA
      catheter. Successful catheter ablation was achieved at the ventricular site
      between those electrode pairs. A Halo-type catheter may be effective for mapping
      and catheter ablation of ventricular arrhythmias originating from the TA.

PMID- 18621769
TI  - Reduction of complex ventricular ectopy and improvement in exercise capacity with
      flecainide therapy in Andersen-Tawil syndrome.
AB  - Andersen-Tawil syndrome (ATS) is a rare inherited autosomal disorder
      characterized by the clinical triad of ventricular arrhythmias, hypokalaemic
      periodic paralyses, and skeletal developmental abnormalities, resulting in
      dysmorphic features. Although ATS patients have a high incidence of ventricular
      arrhythmias, the occurrence of sudden cardiac death is rare. In this report, we
      describe the successful use of flecainide in an ATS patient with a considerable
      ventricular arrhythmia burden who had not demonstrated any response to
      conventional beta-blocker therapy used in conjunction with potassium (K(+))
      supplementation.

PMID- 18621770
TI  - Improvement of regional myocardial blood flow and function and reduction of
      infarct size with ivabradine: protection beyond heart rate reduction.
AB  - AIMS: Effects of the bradycardic agent ivabradine on regional blood flow,
      contractile function, and infarct size were studied in a pig model of myocardial
      ischaemia/reperfusion. Heart rate reduction by beta-blockade is associated with
      negative inotropism and unmasked alpha-adrenergic coronary vasoconstriction.
      Ivabradine is the only available bradycardic agent for clinical use. METHODS AND
      RESULTS: Anaesthetized pigs were subjected to 90 min controlled left anterior
      descending coronary artery hypoperfusion and 120 min reperfusion. Regional blood
      flow was measured with microspheres, regional function with sonomicrometry, and
      infarct size with triphenyl tetrazolium chloride staining. Pigs received placebo
      or ivabradine (0.6 mg/kg i.v.) before or during ischaemia or before reperfusion,
      respectively. Pre-treatment with ivabradine reduced infarct size from 35 +/- 4
      (SEM) to 19 +/- 4% of area at risk (AAR). Ivabradine 15-20 min after the onset of
      ischaemia increased regional myocardial blood flow from 2.12 +/- 0.31 to 3.55 +/-
      0.56 microL/beat/g and systolic wall thickening from 6.7 +/- 1.0 to 16.3 +/-
      3.0%; infarct size was reduced from 12 +/- 4 to 2 +/- 1% of AAR. Ivabradine 5 min
      before reperfusion still reduced infarct size from 36 +/- 4 to 21 +/- 5% of AAR.
      The benefit of ivabradine on flow and function was eliminated by atrial pacing,
      but part of the reduction of infarct size by ivabradine was not. CONCLUSION:
      Ivabradine's protection goes beyond heart rate reduction.

PMID- 18621772
TI  - Electrical remodelling of the left and right atria due to rheumatic mitral
      stenosis.
AB  - AIMS: To characterize the atrial remodelling in mitral stenosis (MS). METHODS AND
      RESULTS: Twenty-four patients with severe MS undergoing commissurotomy and 24
      controls were studied. Electrophysiological evaluation was performed in 12
      patients in each group by positioning multi-electrode catheters in both atria to
      determine the following: effective refractory period (ERP) at 10 sites at 600 and
      450 ms; conduction time; conduction delay at the crista terminalis (CT); and
      vulnerability for atrial fibrillation (AF). P-wave duration (PWD) was determined
      on the surface ECG. In the remaining 12 patients in each group, electroanatomic
      maps of both atria were created to determine conduction velocity and identify
      regions of low voltage and electrical silence. Patients with MS had larger left
      atria (LA) (P < 0.0001); prolonged PWD (P = 0.0007); prolonged ERP in both LA (P
      < 0.0001) and right atria (RA) (P < 0.0001); reduced conduction velocity in the
      LA (P = 0.009) and RA (P < 0.0001); greater number (P < 0.0001) and duration (P<
      0.0001) of bipoles along the CT with delayed conduction; lower atrial voltage in
      the LA (P < 0.0001) and RA (P < 0.0001); and more frequent electrical scar (P =
      0.001) compared with controls. Five of twelve with MS and none of the controls
      developed AF with extra-stimulus (P = 0.02). CONCLUSION: Atrial remodelling in MS
      is characterized by LA enlargement, loss of myocardium, and scarring associated
      with widespread and site-specific conduction abnormalities and no change or an
      increase in ERP. These abnormalities were associated with a heightened
      inducibility of AF.

PMID- 18621771
TI  - Contribution of novel biomarkers to incident stable angina and acute coronary
      syndrome: the PRIME Study.
AB  - AIMS: To compare whether novel inflammatory and haemostatic biomarkers are more
      predictive of well-characterized incident acute coronary syndrome (ACS) than
      stable angina (SA). METHODS AND RESULTS: We used data from the PRIME Study, a
      prospective cohort of 9758 asymptomatic middle-aged men recruited in Northern
      Ireland and France between 1991 and 1993. A nested case-control study was
      established with the baseline plasma sample of 269 incident cases and 538 matched
      controls. Odds ratios (ORs) for SA and ACS were estimated by conditional logistic
      regression analysis. After 5 years of follow-up, 107 incident SA and 162 ACS
      cases were validated. After adjustment for traditional risk factors, higher
      circulating levels of hs-CRP, ICAM1, interleukin 6 and interleukin 18 were
      equally predictive of SA and ACS (all P-values of OR comparison >0.05). In
      contrast, elevated levels of fibrinogen, von Willebrand factor, and possibly
      higher level of D-dimers and lower level of tissue factor pathway inhibitor were
      associated with ACS only. The comparison of the ORs showed a statistically
      significant difference for von Willebrand factor only [OR(4th vs. 1st quartile) =
      2.99 (1.49-6.02) for ACS vs. 0.80 (0.33-1.94) for SA; P(z test) = 0.02].
      CONCLUSION: This is the first population-based study suggesting that higher
      levels of circulating haemostatic markers and of von Willebrand factor, in
      particular, are significantly more predictive of incident ACS than SA.

PMID- 18621773
TI  - Assessment and relevance of ventricular wall stress in heart failure.

PMID- 18621774
TI  - Acute and stable coronary heart disease: different risk factors.

PMID- 18621775
TI  - The hypoxic ischaemic encephalopathy score in predicting neurodevelopmental
      outcomes among infants with birth asphyxia at the Muhimbili National Hospital,
      Dar-es-Salaam, Tanzania.
AB  - Hypoxic Ischemic Encephalopathy (HIE) score may be used to predict
      neurodevelopment outcome in infants with birth asphyxia. A total of 140 infants
      who had a 5 min Apgar score of <7 at birth had detailed motor and
      neurodevelopment assessment. Outcome measures were grouped as normal or abnormal
      with morbidity (convulsions, abnormal muscle tone and delayed development) or
      death. The positive predictive value (PPV) for mortality was 42.3% for moderate
      HIE and 93.8% for severe HIE. For severe HIE the PPV was 100%. Thirteen infants
      had delayed development, the score had PPV of 63.6% for moderate HIE and 100% for
      severe HIE. The best correlation with outcome was the peak score of 15 or higher
      had a PPV of 100%. Specificity was found to be 100% and sensitivity of 14%. The
      HIE scoring system is a useful predictor of neurodevelopment outcome at 6 months
      of age in a resource poor setting.

PMID- 18621776
TI  - Income and short-term case fatality after myocardial infarction in the whole
      middle-aged population of Malmo, Sweden.
AB  - BACKGROUND: There are no previous studies investigating when and where those who
      die pre-hospitally after an AMI paid their last visit to medical care. METHODS
      AND RESULTS: Incidence of AMI, pre-hospital and 28-day case fatality rates were
      monitored over 13 years of follow-up, in relation to sex-specific quartiles of
      annual income in all inhabitants aged 40-64 years in Malmo, Sweden. Both
      incidence and short-term case fatality were inversely related to income. In all,
      60-70% of all deaths within 28 days after the AMI were pre-hospital deaths. As
      compared with the lowest income group, the highest income group had lower odds of
      pre-hospital death with an age- and time-to-event-adjusted odds ratio of 0.5 (95%
      CI 0.4-0.8) for men and 0.3 (95% CI 0.1-0.6) for women. On the other hand, while
      72% of those in the lowest two income groups had paid a visit to the medical
      services during the three months before death, only 59% had done so in the two
      highest income groups (P < 0.05). CONCLUSIONS: Poor socioeconomic circumstances
      increase the risk of pre-hospital death after an AMI. Of the pre-hospital deaths,
      the proportion who had visited the medical services during the 3 months preceding
      their AMI was higher among those from lower income groups. However, many of those
      suffering a pre-hospital death had visited clinics that normally do not treat
      coronary symptoms. If more patients were identified at an earlier stage this
      might increase the number of patients reaching hospital alive.

PMID- 18621777
TI  - Risk-adjustment model in health outcomes evaluation: a contribution to strengthen
      assessment towards quality improvement in interventional cardiology.
AB  - OBJECTIVE: The aim of this study was to develop a risk adjustment model for major
      adverse cardiac and cerebrovascular events following percutaneous coronary
      intervention (PCI), using data from a national registry, and to highlight the use
      of the risk adjustment when we evaluate the quality of care in interventional
      cardiology. DESIGN: The STUDY DESIGN: was based on a Coorte study. Bivariate and
      multivariate logistic regression models were used to identify independent risk
      factors for these major adverse events. SETTING: A total of 19 hospitals from the
      Portuguese National Registry of Interventional Cardiology. PARTICIPANTS: Data
      from 10.641 consecutives procedures collected between June 30, 2003 and June 30,
      2006. INTERVENTION: Build a risk adjustment model for these major adverse events,
      following percutaneous coronary intervention. MAIN OUTCOME MEASURE: Factors that
      were associated with major adverse cardiac and cerebrovascular events following
      percutaneous coronary intervention. RESULTS: The rate of in-hospital major
      adverse cardiac and cerebrovascular events was 1.9%. Factors associated with
      major adverse cardiac and cerebrovascular events included, among others: age >80
      years (adjusted odds ratio = 3.91); female gender (1.72); and cardiogenic shock
      (6.05). Overall, a good discrimination was achieved with receiver operating
      characteristics curve = 0.84 and Hosmer-Lemeshow goodness of fit statistic across
      groups of risk was not significant (P = 0.18) indicating little departure from a
      perfect fit. CONCLUSIONS: These findings will represent an important contribution
      to quality and safety improvement and should help driving new research and
      innovative approaches to different subgroups of patients who have higher chances
      of having an adverse event or poorer outcomes following this intervention.

PMID- 18621778
TI  - Content of antenatal care services in secondary health care facilities in
      Nigeria: implication for quality of maternal health care.
AB  - OBJECTIVE: To assess the contents of antenatal care and to relate the findings to
      the adequacy of maternal health care. DESIGN: Cross-sectional study. SETTING:
      Public secondary health-care facilities. PARTICIPANTS: Pregnant women.
      INTERVENTIONS: Three hundred and ninety consecutive pregnant women attending 12
      selected secondary health facilities were recruited proportionate to the client
      load recorded for each facility during the year preceding the study. Interviews
      were conducted using the antenatal care exit interview form of the Safe
      Motherhood Needs Assessment package. MAIN OUTCOME MEASURES: Antenatal care
      services provided to pregnant women in current pregnancy. RESULTS: Blood pressure
      measurement, abdominal palpation and detection of foetal heart rate were provided
      to all participants. Three hundred and eighty-six (99%) were reached with at
      least one educational message. One hundred and sixty-seven (42.8%) had
      haemoglobin or packed cell volume estimated, whereas 168 (43.1%) had urine
      checked for protein, at least once during antenatal visits. Routine iron and
      folate supplements, and malaria prophylaxis were, respectively, given to 142
      (36.4%) and 25 (6.4%). CONCLUSIONS: The antenatal care service as provided had
      reasonable capacity for intervention against pre-eclampsia and some foetal
      problems, and could contribute to delivery in a health facility and by a health
      worker. Capacity to address the possible effects of severe anaemia and malaria in
      pregnancy was lacking. Equipping health-care facilities with capacity to detect
      anaemia and proteinuria as well as ensuring that iron and folate supplements, and
      malaria prophylaxis are given to all pregnant women would help to meet national
      guidelines and improve quality of service.

PMID- 18621779
TI  - Caring for children: a model of healthcare service quality in Bangladesh.
AB  - OBJECTIVE: This study assesses the links between service quality and patient
      satisfaction in the context of health services delivered to children in a
      developing country. With the growing importance of patients' voice in the
      healthcare environment, it is important to assess the factors that are best able
      to explain patient satisfaction to influence the art and science of patient care
      and health service delivery. DESIGN: A field survey was conducted using a
      household survey to assess the quality of services provided to children who had
      been to a hospital in the past 12 months. PARTICIPANTS: Caregivers who had
      accompanied an afflicted child to a hospital in Dhaka City. MAIN OUTCOME
      MEASURES: Patient satisfaction was the main outcome/dependent variable as
      reflected in surrogate measures obtained from the children's accompanying
      caregivers. RESULTS: A regression model was tested. The independent variables
      were nurse composite, doctor composite, tangibles, health inputs and facilitation
      payments. The model explained 67.4% of the variation in the dependent variable
      (R(2)). The behavior of nurses had the greatest impact on satisfaction (P <
      0.001) as reflected in the standardized betas, followed by the behavior of
      doctors (P < 0.001). Facilitation payments had a negative effect on satisfaction
      (P < 0.01). CONCLUSIONS: Bringing about attitude change among doctors, nurses and
      support staff is vital for improving children's satisfaction with hospital care.
      Installing proper recruitment procedures, training, supervision, and reward
      systems are most likely to facilitate this change. But similar changes are also
      needed elsewhere: in the Ministry of Health and Family Welfare, other
      facilitating ministries, as well as the development partners to achieve enduring
      and positive effects.

PMID- 18621780
TI  - Shone's syndrome diagnosed with echocardiography and confirmed at pathology.
AB  - The Shone's complex, defined by four cardiovascular defects such as a
      supravalvular mitral membrane, valvular mitral stenosis by a parachute mitral
      valve, subaortic stenosis, and aortic coarctation, is a rare entity, which occurs
      most frequently in its incomplete form. We report the case of a 19-year-old
      female patient who presented at the emergency room for progressively worsening
      dyspnoea, orthopnoea, fever, and productive cough, due to bronchopneumonia.
      Echocardiography revealed the co-existence of aortic coarctation with bicuspid
      aortic valves, mitral supravalvular ring, and dysplastic mitral valves producing
      severe mitral stenosis and severe pulmonary hypertension. Although wide spectrum
      antibiotics were administered from the first day of hospitalization, the patient
      developed severe sepsis and died. The components of the Shone's complex diagnosed
      by echocardiography were confirmed at pathology.

PMID- 18621781
TI  - Anomalous insertion of the papillary muscle causing left ventricular outflow
      obstruction: visualization by real-time three-dimensional echocardiography.
AB  - Anomalous insertion of the papillary muscle (PM)/chordae tendineae is a rare but
      important cause of dynamic left ventricular outflow tract (LVOT) obstruction in
      patients with hypertrophic cardiomyopathy or cardiac amyloidosis. These anomalies
      are often challenging to diagnose with 2-D Echo, yet accurate diagnosis is
      critical in determining whether to proceed with an extended septal myectomy
      instead of a standard septal myectomy for relief. We report two cases of
      anomalous insertion of the PM causing LVOT obstruction with diagnosis facilitated
      by real-time 3-D echocardiograms.

PMID- 18621782
TI  - Preferential heterodimerization of a bispecific diabody based on a humanized anti
      EGFR antibody 528.
AB  - We report the utility of in vitro refolding in the preparation of monomorphous
      hEx3 bispecific diabodies with epidermal growth factor receptor and CD3
      retargeting from insoluble aggregates in Escherichia coli. Appropriate
      interaction between cognate variable heavy and light chains led to the formation
      of functional hEx3 heterodimers in a diabody format rather than inactive
      homodimers. The refolded hEx3 was found to exhibit almost the equivalent activity
      to the hEx3 and single-chain hEx3 (hEx3-scDb) prepared in a mammalian secretion
      system. We suggest that the preparation of hEx3 from bacterial insoluble material
      by means of in vitro refolding would be useful for industrial-scale production of
      the diabody for its potential use in clinical studies.

PMID- 18621783
TI  - Spatial configuration of the chicken alpha-globin gene domain: immature and
      active chromatin hubs.
AB  - The spatial configuration of the chicken alpha-globin gene domain in erythroid
      and lymphoid cells was studied by using the Chromosome Conformation Capture (3C)
      approach. Real-time PCR with TaqMan probes was employed to estimate the
      frequencies of cross-linking of different restriction fragments within the
      domain. In differentiated cultured erythroblasts and in 10-day chick embryo
      erythrocytes expressing 'adult' alpha(A) and alpha(D) globin genes the following
      elements of the domain were found to form an 'active' chromatin hub: upstream
      Major Regulatory Element (MRE), -9 kb upstream DNase I hypersensitive site (DHS),
      -4 kb upstream CpG island, alpha(D) gene promoter and the downstream enhancer.
      The alpha(A) gene promoter was not present in the 'active' chromatin hub although
      the level of alpha(A) gene transcription exceeded that of the alpha(D) gene.
      Formation of the 'active' chromatin hub was preceded by the assembly of multiple
      incomplete hubs containing MRE in combination with either -9 kb DHS or other
      regulatory elements of the domain. These incomplete chromatin hubs were present
      in proliferating cultured erythroblasts which did not express globin genes. In
      lymphoid cells only the interaction between the alpha(D) promoter and the CpG
      island was detected.

PMID- 18621784
TI  - From risk factors to explanation in public health.

PMID- 18621785
TI  - Causes in epidemiology: the jewels in the public health crown.

PMID- 18621786
TI  - Explanations in practice.

PMID- 18621787
TI  - Explanations adequate for public health.

PMID- 18621788
TI  - Towards a realistic and relevant public health: the challenges of useful
      simplification.

PMID- 18621790
TI  - Detection of visual-field deterioration by Glaucoma Progression Analysis and
      Threshold Noiseless Trend programs.
AB  - BACKGROUND: To compare the ability of Glaucoma Progression Analysis (GPA) and
      Threshold Noiseless Trend (TNT) programs to detect visual-field deterioration.
      METHODS: Patients with open-angle glaucoma followed for a minimum of 2 years and
      a minimum of seven reliable visual fields were included. Progression was assessed
      subjectively by four masked glaucoma experts, and compared with GPA and TNT
      results. Each case was judged to be stable, deteriorated or suspicious of
      deterioration RESULTS: A total of 56 eyes of 42 patients were followed with a
      mean of 7.8 (SD 1.0) tests over an average of 5.5 (1.04) years. Interobserver
      agreement to detect progression was good (mean kappa = 0.57). Progression was
      detected in 10-19 eyes by the experts, in six by GPA and in 24 by TNT. Using the
      consensus expert opinion as the gold standard (four clinicians detected
      progression), the GPA sensitivity and specificity were 75% and 83%, respectively,
      while the TNT sensitivity and specificity was 100% and 77%, respectively.
      CONCLUSION: TNT showed greater concordance with the experts than GPA in the
      detection of visual-field deterioration. GPA showed a high specificity but lower
      sensitivity, mainly detecting cases of high focality and pronounced mean defect
      slopes.

PMID- 18621791
TI  - Long-term efficacy and safety of bimatoprost for intraocular pressure lowering in
      glaucoma and ocular hypertension: year 4.
AB  - BACKGROUND: Bimatoprost 0.03% has been shown to consistently reduce mean
      intraocular pressure (IOP) more than timolol 0.5% over 2 years. To further
      evaluate long-term safety and efficacy, once-daily bimatoprost 0.03% was compared
      with timolol 0.5% twice daily through year 4. METHODS: In this multicentre,
      double-masked, randomised, controlled trial, glaucoma and ocular hypertension
      patients (n = 152) who completed phase III bimatoprost trials through month 36
      were enrolled in a study extension through month 48. Patients randomised to
      bimatoprost once daily (n = 78) or timolol twice daily (n = 35) continued on the
      same regimen for a fourth year. Patients randomised to bimatoprost twice daily
      had been switched to bimatoprost once daily dosing at month 24 (bimatoprost twice
      daily/once daily treatment group), and continued with once daily dosing through
      month 48 (n = 39). IOP was measured at 08:00 and 10:00 at months 39, 42, 45 and
      48. Safety measures included adverse events, biomicroscopy, ophthalmoscopy,
      visual acuity and visual field. RESULTS: Baseline IOP was comparable among
      groups. During year 4, mean IOP reductions from baseline were 7.0 to 8.1 mm Hg
      with bimatoprost once daily and 6.5 to 7.9 mm Hg with bimatoprost twice
      daily/once daily, significantly greater than with timolol twice daily (3.8 to 5.8
      mm Hg, p< or =0.035) at all measurements. Over 4 years, the mean IOP reduction
      from baseline at 08:00 and 10:00 was 1.9 to 3.9 mm Hg (35% to 100%) greater with
      bimatoprost once daily than with timolol (p< or =0.013). Low IOPs were achieved
      by more bimatoprost than timolol patients (p< or =0.042). No safety concerns
      developed during long-term bimatoprost treatment; two patients in the timolol
      treatment group discontinued after month 36 because of adverse events. The most
      common treatment-related adverse event in the bimatoprost treatment groups was
      conjunctival hyperaemia. CONCLUSION: Bimatoprost once daily provided sustained
      IOP lowering greater than timolol twice daily and was well tolerated over long
      term use.

PMID- 18621792
TI  - Wearing swimming goggles can elevate intraocular pressure.
AB  - AIM: To examine the acute effects of wearing swimming goggles upon intraocular
      pressure (IOP). METHODS: This research consisted of a Pilot study and a
      Validation study. Holes were drilled into the faces of 13 different goggles to
      allow IOP measurement by applanation tonometry. IOP was measured before goggles
      wear, 2 min after goggles application, 20 min after goggles application and after
      goggles removal. The Pilot study (n = 15) was initially performed to investigate
      changes in IOP while wearing five different types of swimming goggles. Anatomical
      and goggles design parameters from the Pilot study were then used to generate a
      predictive model and design a Validation study (n = 20). The Validation study
      tested the predictive model, examined IOP changes using another eight goggles and
      clarified whether IOP changes were sustained for the duration of goggles wear.
      RESULTS: IOP increased while wearing goggles by a mean pressure of 4.5 mm Hg (SD
      3.7, p<0.001) with this pressure rise being sustained for the duration of goggles
      wear. A smaller goggles face area (p = 0.013), was consistently associated with
      greater IOP elevation. CONCLUSION: These measurements were not taken while
      swimming, but they suggest that some swimming goggles can elevate IOP.

PMID- 18621793
TI  - Filling in at partially deafferented visual cortex.
AB  - METHODS: Perceptual visual filling in at the corresponding area of toxoplasmic
      retinochoroiditis scotomas in the fellow eye was studied in 14 patients. Targets
      were programmed to appear inside the scotoma corresponding area in the fellow
      eye, and at two control points. RESULTS: The results showed faster perceptual
      filling-in latencies (p<0.0001) in the scotoma corresponding area than at the
      control points. CONCLUSIONS: Perceptual filling in is facilitated at the
      corresponding area of retinal scotomas. The neural mechanisms of this visual
      facilitation might be similar to those found following somatosensory cortex
      partial deafferentation.

PMID- 18621794
TI  - Incidence of retinoblastoma in the USA: 1975-2004.
AB  - BACKGROUND: The purpose of this study was to determine the age-adjusted incidence
      of retinoblastoma in the USA over a 30-year period from 1975 to 2004 using a
      review of existing databases. METHODS: Six hundred and fifty-eight patients with
      retinoblastoma (International Classification of Oncology (ICDO-3) codes C69.2
      (retina) and C69.9 (eye, NOS)) were derived from the Surveillance, Epidemiology,
      and End Results (SEER) program database in the USA from 1975 to 2004. Nine
      historical SEER registries were utilised. The significance of trend in age
      adjusted incidence rate was determined using the chi(2) test, and 95% CIs were
      calculated. The patients were stratified according to age at diagnosis,
      laterality, gender and race. RESULTS: There were a total of 658 cases of
      retinoblastoma, representing 6.1% of all childhood cancers under age 5 years. The
      mean age-adjusted incidence of retinoblastoma in the USA was 11.8 per million
      children aged 0-4 years (95% CI 10.9 to 12.8). There was no significant trend in
      age-adjusted incidence for all races/genders, nor was there any significant
      variation of incidence between races or between genders. The proportion of
      bilateral cases (26.7%) versus unilateral cases (71.9%) remained stable over the
      30-year period. CONCLUSIONS: The mean age-adjusted incidence rate of
      retinoblastoma of 11.8 cases per million children aged 0-4 years in the USA is
      similar to rates reported from European countries. The age-adjusted incidence
      rate of retinoblastoma in the USA has remained stable for the last 30 years.

PMID- 18621795
TI  - Longitudinal analysis of corneal topography in suspected keratoconus.
AB  - AIMS: To examine the incidence of progression of suspected keratoconus to true
      keratoconus and compare quantitative descriptors of corneal topography between
      eyes with and without progression. METHODS: 34 eyes with suspected keratoconus
      were retrospectively reviewed in 34 patients. Their age at the initial
      examination was 13 to 40 years (24.1 (7.5), mean (SD)), and the follow-up periods
      ranged from 3 to 10 years (6.0 (2.2) years). Suspected keratoconus was defined as
      the fellow eye of a clinically apparent keratoconus but that had no slit-lamp
      signs of keratoconus (Fleischer ring, Vogt striae and Munson sign) with a best
      spectacle-corrected visual acuity of 20/20 or better. Eyes were monitored for the
      progression of apparent slit-lamp findings of keratoconus during the follow-up
      period. Using a Fourier analysis of the corneal topography data, regular
      astigmatism, asymmetry component and higher-order irregularity component were
      calculated in the central 3 mm zone. Quantitative descriptors of corneal
      topography were compared between eyes which progressed to true keratoconus and
      those which did not. RESULTS: Five eyes (14.7%) progressed to apparent
      keratoconus from suspected keratoconus (progression group), and 29 eyes did not
      (non-progression group). On average, it took 5.2 years for the eyes to develop
      apparent slit-lamp findings of keratoconus. The cumulative incidence of
      progression by Kaplan-Meier analysis was 21.5% in 6 years. The asymmetry
      component and regular astigmatism by Fourier analysis at the initial examination
      were significantly larger in the progression group than in the non-progression
      group. CONCLUSION: In our retrospective study, approximately 20% of eyes with
      suspected keratoconus progressed to true keratoconus in 6 years, and these eyes
      had presented greater asymmetry and regular astigmatism at the initial
      examination.

PMID- 18621796
TI  - Efficacy of intravitreal injection of bevacizumab for severe retinopathy of
      prematurity: a pilot study.
AB  - AIM: The aim of the study was to evaluate the short-term efficacy of intravitreal
      injections of bevacizumab for severe retinopathy of prematurity (ROP). METHODS: A
      retrospective chart review was conducted of 23 consecutive eyes (stage 3, three
      eyes; 4A, 18 eyes; 4B, two eyes) of 14 patients with vascularly active ROP
      considered at high risk for progression or development of tractional retinal
      detachment despite conventional laser ablation therapy. Patients received an
      intravitreal injection of bevacizumab (0.5 mg), either as the initial treatment
      (15 eyes) or at the end of vitrectomy (eight eyes). RESULTS: After injection of
      bevacizumab as the initial treatment, reduced neovascular activity was seen on
      fluorescein angiography in 14 of 15 eyes. In three eyes, a tractional retinal
      detachment developed or progressed after bevacizumab injection. No other ocular
      or systemic adverse effects were identified. Vitrectomy was performed in 20 eyes
      and the retina was reattached after one surgery in 18 eyes. Multiple surgeries
      were necessary in two eyes, resulting in retinal reattachment. CONCLUSION: There
      results suggest that intravitreal injection of bevacizumab seems to be associated
      with reduced neovascularisation without apparent ocular or systemic adverse
      effects, and is thus beneficial for treating severe ROP that is refractory to
      conventional laser therapy.

PMID- 18621797
TI  - Fibrin glue versus sutures for conjunctival autografting in pterygium surgery: a
      prospective comparative study.
AB  - AIM: To compare the use of fibrin glue versus sutures for fixating conjunctival
      autografts in patients undergoing pterygium excision. METHODS: Fifty patients (50
      eyes) with primary pterygium were randomised to undergo pterygium surgery using
      either fibrin glue (25 eyes) or 8-0 Vicryl sutures (25 eyes) to attach the
      conjunctival autograft. The patients were followed up for 12 months. Outcome
      measures were postoperative patient comfort, duration of surgery and recurrence
      of pterygium. RESULTS: In the fibrin glue group, the mean operation time was 15.7
      (SD 2.4) min (range 12-18 min) and in the suture group (p<0.001) it was 32.5
      (6.7) min (range 25-40 min). The intensity of the postoperative pain, foreign
      body sensation, irritation and epiphora were significantly lower in the fibrin
      glue group than in the suture group (p<0.001). The intensity of itchy sensation
      at the first two postoperative visits was lower among patients in the fibrin glue
      group (five patients, 20%) than in the suture group (12 patients, 48%) (p<0.05).
      Two patients in the fibrin glue group had partial graft dehiscence; these grafts
      were successfully reattached with fibrin glue. At the end of follow-up, pterygium
      recurrence was observed in one eye (4%) in the fibrin glue group and in three
      eyes (12%) in the suture group (p<0.05). CONCLUSION: The use of fibrin glue in
      pterygium surgery with conjunctival autografting significantly reduces surgery
      time, improves postoperative patient comfort and results in a lower recurrence
      rate compared with suturing.

PMID- 18621798
TI  - Treatment of peripapillary choroidal neovascular membranes with intravitreal
      bevacizumab.
AB  - AIMS: To evaluate the effect of intravitreal injections of bevacizumab in the
      treatment of peripapillary choroidal neovascular membranes. METHODS:
      Interventional case series of patients with active peripapillary choroidal
      neovascular membranes. Ophthalmological examination included best-corrected
      visual acuity, fundus biomicroscopy, fluorescein angiography and optical
      coherence tomography (OCT). Bevacizumab injections (1.25 mg) were repeated
      monthly for the first 3 months. Re-treatment was considered if there were any
      signs of membrane activity. RESULTS: Six eyes of five patients with peripapillary
      choroidal membranes were included in the study with a mean follow-up of 13 months
      (range 6 to 16). Bevacizumab was used as the initial treatment in four eyes and
      to manage recurrences after surgery in the other two. In five eyes, three
      injections of bevacizumab led to a complete resolution of leakage on fluorescein
      angiography and OCT. In one eye, membrane activity persisted despite six
      injections of bevacizumab. Visual acuity improved in five eyes with a mean
      improvement of four lines (range: 2-10 lines). It deteriorated only in the eye
      that did not respond to treatment. CONCLUSIONS: The results of this case series
      suggest that the intravitreal injection of bevacizumab may be an effective
      treatment for peripapillary choroidal membranes.

PMID- 18621799
TI  - What is systems biology?

PMID- 18621800
TI  - Influence of liver biopsy on abstinence in alcohol-dependent patients.
AB  - BACKGROUND: Liver biopsy indication for the evaluation of alcoholic liver disease
      is controversial. Our aim was to investigate the influence of the biopsy on the
      patients' motivation for abstinence. METHODS: We retrospectively analysed, in a
      population of 324 patients hospitalized for alcohol withdrawal, the impact of
      liver biopsy on the following clinical outcomes: rapid loss to follow-up
      (immediately after hospital discharge), early relapse (< 3 months) and long
      lasting abstinence (> 12 months). The biopsy was performed in 136 patients who
      had liver enzymes perturbations. Hepatic lesions were graded as mild (isolated
      steatosis and/or non-bridging fibrosis), moderate (bridging fibrosis and/or
      moderate alcoholic hepatitis) or severe (cirrhosis and/or marked alcoholic
      hepatitis) in 66 (48%), 41 (30%) and 29 (21%) cases, respectively. RESULTS: In
      univariate analysis, patients who had a liver biopsy were less likely to be
      rapidly lost to follow-up (12% versus 27%, P = 0.003) but had a lower rate of
      long-term abstinence (20% versus 34%, P = 0.025). In multivariate analysis, age
      was the only factor significantly associated with clinical outcome: older
      patients had higher rate of long-term abstinence (OR = 1.041; P = 0.010). Among
      patients who had a biopsy, those with severe hepatic lesions had a lower rate of
      rapid relapse than those with moderate or mild lesions (32% versus 68% and 56%, P
      = 0.018) but the rate of long-term abstinence was similar in the three groups.
      CONCLUSION: This observational study does not support the notion that liver
      biopsy has a significant influence on the maintenance of alcohol abstinence in
      patients with alcoholic liver disease.

PMID- 18621801
TI  - Proteasome inhibition and stress compromise the heart in chemotherapy.

PMID- 18621802
TI  - Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental
      autoimmune myocarditis.
AB  - AIMS: Experimental autoimmune myocarditis (EAM) is a CD4(+) T cell-mediated mouse
      model of inflammatory heart disease. Tissue-resident bone marrow-derived cells
      adopt different cellular phenotypes depending on the local milieu. We expanded a
      specific population of bone marrow-derived prominin-1-expressing progenitor cells
      (PPC) from healthy heart tissue, analysed their plasticity, and evaluated their
      capacity to protect mice from EAM and heart failure. METHODS AND RESULTS: PPC
      were expanded from healthy mouse hearts. Analysis of CD45.1/CD45.2 chimera mice
      confirmed bone marrow origin of PPC. Depending on in vitro culture conditions,
      PPC differentiated into macrophages, dendritic cells, or cardiomyocyte-like
      cells. In vivo, PPC acquired a cardiac phenotype after direct injection into
      healthy hearts. Intravenous injection of PPC into myosin alpha heavy
      chain/complete Freund's adjuvant (MyHC-alpha/CFA)-immunized BALB/c mice resulted
      in heart-specific homing and differentiation into the macrophage phenotype.
      Histology revealed reduced severity scores for PPC-treated mice compared with
      control animals [treated with phosphate-buffered saline (PBS) or crude bone
      marrow at day 21 after MyHC-alpha/CFA immunization]. Echocardiography showed
      preserved fractional shortening and velocity of circumferential shortening in PPC
      but not PBS-treated MyHC-alpha/CFA-immunized mice. In vitro and in vivo data
      suggested that interferon-gamma signalling on PPC was critical for nitric oxide
      mediated suppression of heart-specific CD4(+) T cells. Accordingly, PPC from
      interferon-gamma receptor-deficient mice failed to protect MyHC-alpha/CFA
      immunized mice from EAM. CONCLUSION: Prominin-1-expressing, heart-resident, bone
      marrow-derived cells combine high plasticity, T cell-suppressing capacity, and
      anti-inflammatory in vivo effects.

PMID- 18621804
TI  - Commentary: Clustering in Down syndrome.

PMID- 18621803
TI  - A protective effect of the Mediterranean diet for cutaneous melanoma.
AB  - BACKGROUND: Many studies have investigated the Mediterranean diet as a risk
      factor for cancer, none of which has included cutaneous melanoma. The latter is
      usually fatal, rendering knowledge about prevention extremely important. We
      assessed the role of some food components of the Mediterranean diet and cutaneous
      melanoma. METHODS: A hospital-based case-control study was conducted in the
      inpatient wards of IDI-San Carlo Rome, Italy including 304 incident cases of
      cutaneous melanoma and 305 controls, frequency matched to cases. Information on
      socio-demographic characteristics, medical history, smoking, sun exposure,
      pigmentary characteristics and diet was collected. Logistic regression was the
      method used to estimated odds ratio and 95% CIs. RESULTS: After careful control
      for several sun exposure and pigmentary characteristics, we found a protective
      effect for weekly consumption of fish (OR, 0.65, 95%CI = 0.43-0.97), shellfish
      (OR, 0.53, 95%CI = 0.31-0.89), fish rich in n-3 fatty acids (OR, 0.52, 95%CI =
      0.34-0.78), daily tea drinking (OR, 0.42, 95%CI, 0.18-0.95; P(trend) = 0.025) and
      high consumption of vegetables (OR, 0.50, 95%CI = 0.31-0.80, P(trend) = 0.005) in
      particular carrots, cruciferous and leafy vegetables and fruits (OR, 0.54, 95%CI
      =0.33-0.86, P(trend) = 0.013), in particular citrus fruits. No association was
      found for alcohol consumption and any other food items. CONCLUSION: Overall, our
      findings suggest that some dietary factors present in the Mediterranean diet
      might protect from cutaneous melanoma.

PMID- 18621805
TI  - Factors that affect longevity of intravenous cannulas: a prospective study.
AB  - BACKGROUND: Few guidelines exist to guide medical personnel on the most
      successful means of achieving sustained intravenous cannulation. This study
      examines the impact of gauge and site of intravenous cannulas (IC) on the
      longevity of ICs in hospitalized patients. METHODS: A prospective study was
      conducted on 500 ICs inserted into patients of St Vincent's Private hospital from
      December 2005 to June 2006. Patients were followed until the IC had been removed
      or changed. Statistical analysis was performed using Cox proportional hazards.
      RESULTS: Of the 500 ICs inserted, 37% were 18 g, 46% were 20 g and 18% were 22 g.
      Gauge of IC was the most significant predictor of increased longevity of IC (P =
      0.0002, RR = 1.17, 95% CI 1.08-1.27). The median survival of 18, 20 and 22 g were
      57 h (95% CI 49-72), 43 h (95% CI 36-48.5) and 29 h (95% CI 24-40.5),
      respectively. The site of IC placement influenced the longevity of ICs (P =
      0.005, RR= 0.7, 95% CI 0.55-0.9), as did male gender (P = 0.03, RR = 0.76, 95% CI
      0.6-0.97). However in subgroup analysis, the most marked effect on IC longevity
      was evident in those patients with 18 g placed in the forearm/wrist (median 72 h)
      with less marked changes in other site/gauge combinations. In contrast, 22 g ICs
      placed in the hand had a median lifespan of 29 h. CONCLUSION: IC gauge and site
      of placement are important factors in determining IC longevity. 18 g ICs placed
      in the forearm/wrist can considerably increase the longevity of ICs and should be
      attempted in patients who require sustained cannulation.

PMID- 18621806
TI  - Stability of adhesion clusters and cell reorientation under lateral cyclic
      tension.
AB  - This work is motivated by experimental observations that cells on stretched
      substrate exhibit different responses to static and dynamic loads. A model of
      focal adhesion that can consider the mechanics of stress fiber, adhesion bonds,
      and substrate was developed at the molecular level by treating the focal adhesion
      as an adhesion cluster. The stability of the cluster under dynamic load was
      studied by applying cyclic external strain on the substrate. We show that a
      threshold value of external strain amplitude exists beyond which the adhesion
      cluster disrupts quickly. In addition, our results show that the adhesion cluster
      is prone to losing stability under high-frequency loading, because the receptors
      and ligands cannot get enough contact time to form bonds due to the high-speed
      deformation of the substrate. At the same time, the viscoelastic stress fiber
      becomes rigid at high frequency, which leads to significant deformation of the
      bonds. Furthermore, we find that the stiffness and relaxation time of stress
      fibers play important roles in the stability of the adhesion cluster. The essence
      of this work is to connect the dynamics of the adhesion bonds (molecular level)
      with the cell's behavior during reorientation (cell level) through the mechanics
      of stress fiber. The predictions of the cluster model are consistent with
      experimental observations.

PMID- 18621809
TI  - Stochastic simulation of enzyme-catalyzed reactions with disparate timescales.
AB  - Many physiological characteristics of living cells are regulated by protein
      interaction networks. Because the total numbers of these protein species can be
      small, molecular noise can have significant effects on the dynamical properties
      of a regulatory network. Computing these stochastic effects is made difficult by
      the large timescale separations typical of protein interactions (e.g., complex
      formation may occur in fractions of a second, whereas catalytic conversions may
      take minutes). Exact stochastic simulation may be very inefficient under these
      circumstances, and methods for speeding up the simulation without sacrificing
      accuracy have been widely studied. We show that the "total quasi-steady-state
      approximation" for enzyme-catalyzed reactions provides a useful framework for
      efficient and accurate stochastic simulations. The method is applied to three
      examples: a simple enzyme-catalyzed reaction where enzyme and substrate have
      comparable abundances, a Goldbeter-Koshland switch, where a kinase and
      phosphatase regulate the phosphorylation state of a common substrate, and coupled
      Goldbeter-Koshland switches that exhibit bistability. Simulations based on the
      total quasi-steady-state approximation accurately capture the steady-state
      probability distributions of all components of these reaction networks. In many
      respects, the approximation also faithfully reproduces time-dependent aspects of
      the fluctuations. The method is accurate even under conditions of poor timescale
      separation.

PMID- 18621807
TI  - Self-assembly of a simple membrane protein: coarse-grained molecular dynamics
      simulations of the influenza M2 channel.
AB  - The transmembrane (TM) domain of the M2 channel protein from influenza A is a
      homotetrameric bundle of alpha-helices and provides a model system for
      computational approaches to self-assembly of membrane proteins. Coarse-grained
      molecular dynamics (CG-MD) simulations have been used to explore partitioning
      into a membrane of M2 TM helices during bilayer self-assembly from lipids. CG-MD
      is also used to explore tetramerization of preinserted M2 TM helices. The M2
      helix monomer adopts a membrane spanning orientation in a lipid (DPPC) bilayer.
      Multiple extended CG-MD simulations (5 x 5 micros) were used to study the
      tetramerization of inserted M2 helices. The resultant tetramers were evaluated in
      terms of the most populated conformations and the dynamics of their
      interconversion. This analysis reveals that the M2 tetramer has 2x rotationally
      symmetrical packing of the helices. The helices form a left-handed bundle, with a
      helix tilt angle of approximately 16 degrees. The M2 helix bundle generated by CG
      MD was converted to an atomistic model. Simulations of this model reveal that the
      bundle's stability depends on the assumed protonation state of the H37 side
      chains. These simulations alongside comparison with recent x-ray (3BKD) and NMR
      (2RLF) structures of the M2 bundle suggest that the model yielded by CG-MD may
      correspond to a closed state of the channel.

PMID- 18621808
TI  - In-depth activation of channelrhodopsin 2-sensitized excitable cells with high
      spatial resolution using two-photon excitation with a near-infrared laser
      microbeam.
AB  - We used two-photon excitation with a near-infrared (NIR) laser microbeam to
      investigate activation of channelrhodopsin 2 (ChR2) in excitable cells for the
      first time to our knowledge. By measuring the fluorescence intensity of the
      calcium (Ca) indicator dye, Ca orange, at different wavelengths as a function of
      power of the two-photon excitation microbeam, we determined the activation
      potential of the NIR microbeam as a function of wavelength. The two-photon
      activation spectrum is found to match measurements carried out with single-photon
      activation. However, two-photon activation is found to increase in a nonlinear
      manner with the power density of the two-photon laser microbeam. This approach
      allowed us to activate different regions of ChR2-sensitized excitable cells with
      high spatial resolution. Further, in-depth activation of ChR2 in a spheroid
      cellular model as well as in mouse brain slices was demonstrated by the use of
      the two-photon NIR microbeam, which was not possible using single-photon
      activation. This all-optical method of identification, activation, and detection
      of ChR2-induced cellular activation in genetically targeted cells with high
      spatial and temporal resolution will provide a new method of performing minimally
      invasive in-depth activation of specific target areas of tissues or organisms
      that have been rendered photosensitive by genetic targeting of ChR2 or similar
      photo-excitable molecules.

PMID- 18621810
TI  - Brownian dynamics and molecular dynamics study of the association between
      hydrogenase and ferredoxin from Chlamydomonas reinhardtii.
AB  - The [FeFe] hydrogenase from the green alga Chlamydomonas reinhardtii can catalyze
      the reduction of protons to hydrogen gas using electrons supplied from
      photosystem I and transferred via ferredoxin. To better understand the
      association of the hydrogenase and the ferredoxin, we have simulated the process
      over multiple timescales. A Brownian dynamics simulation method gave an initial
      thorough sampling of the rigid-body translational and rotational phase spaces,
      and the resulting trajectories were used to compute the occupancy and free-energy
      landscapes. Several important hydrogenase-ferredoxin encounter complexes were
      identified from this analysis, which were then individually simulated using
      atomistic molecular dynamics to provide more details of the hydrogenase and
      ferredoxin interaction. The ferredoxin appeared to form reasonable complexes with
      the hydrogenase in multiple orientations, some of which were good candidates for
      inclusion in a transition state ensemble of configurations for electron transfer.

PMID- 18621811
TI  - Microarchitecture of three-dimensional scaffolds influences cell migration
      behavior via junction interactions.
AB  - Cell migration plays a critical role in a wide variety of physiological and
      pathological phenomena as well as in scaffold-based tissue engineering. Cell
      migration behavior is known to be governed by biochemical stimuli and cellular
      interactions. Biophysical processes associated with interactions between the cell
      and its surrounding extracellular matrix may also play a significant role in
      regulating migration. Although biophysical properties of two-dimensional
      substrates have been shown to significantly influence cell migration, elucidating
      factors governing migration in a three-dimensional environment is a relatively
      new avenue of research. Here, we investigate the effect of the three-dimensional
      microstructure, specifically the pore size and Young's modulus, of collagen
      glycosaminoglycan scaffolds on the migratory behavior of individual mouse
      fibroblasts. We observe that the fibroblast migration, characterized by motile
      fraction as well as locomotion speed, decreases as scaffold pore size increases
      across a range from 90 to 150 mum. Directly testing the effects of varying strut
      Young's modulus on cell motility showed a biphasic relationship between cell
      speed and strut modulus and also indicated that mechanical factors were not
      responsible for the observed effect of scaffold pore size on cell motility.
      Instead, in-depth analysis of cell locomotion paths revealed that the
      distribution of junction points between scaffold struts strongly modulates
      motility. Strut junction interactions affect local directional persistence as
      well as cell speed at and away from the junctions, providing a new biophysical
      mechanism for the governance of cell motility by the extracellular
      microstructure.

PMID- 18621812
TI  - Effects of multiple-bond ruptures on kinetic parameters extracted from force
      spectroscopy measurements: revisiting biotin-streptavidin interactions.
AB  - Force spectroscopy measurements of the rupture of the molecular bond between
      biotin and streptavidin often results in a wide distribution of rupture forces.
      We attribute the long tail of high rupture forces to the nearly simultaneous
      rupture of more than one molecular bond. To decrease the number of possible
      bonds, we employed hydrophilic polymeric tethers to attach biotin molecules to
      the atomic force microscope probe. It is shown that the measured distributions of
      rupture forces still contain high forces that cannot be described by the forced
      dissociation from a deep potential well. We employed a recently developed
      analytical model of simultaneous rupture of two bonds connected by polymer
      tethers with uneven length to fit the measured distributions. The resulting
      kinetic parameters agree with the energy landscape predicted by molecular
      dynamics simulations. It is demonstrated that when more than one molecular bond
      might rupture during the pulling measurements there is a noise-limited range of
      probe velocities where the kinetic parameters measured by force spectroscopy
      correspond to the true energy landscape. Outside this range of velocities, the
      kinetic parameters extracted by using the standard most probable force approach
      might be interpreted as artificial energy barriers that are not present in the
      actual energy landscape. Factors that affect the range of useful velocities are
      discussed.

PMID- 18621813
TI  - Taxol allosterically alters the dynamics of the tubulin dimer and increases the
      flexibility of microtubules.
AB  - Taxol is a commonly used antitumor agent that hyperstabilizes microtubules and
      prevents cell division. The interaction of Taxol with tubulin and the microtubule
      has been studied through a wide array of experimental techniques; however, the
      exact molecular mechanism by which Taxol stabilizes microtubules has remained
      elusive. In this study, through the use of large-scale molecular simulations, we
      show that Taxol affects the interactions between the M and H1-S2 loops of
      adjacent tubulin dimers leading to more stable interprotofilament interactions.
      More importantly, we demonstrate that Taxol binding leads to a significant
      increase in the dynamics and flexibility of the portion of beta-tubulin that
      surrounds the bound nucleotide and makes contact with the alpha-monomer of the
      next dimer in the protofilament. We conclude that this increase in flexibility
      allows the microtubule to counteract the conformational changes induced by
      nucleotide hydrolysis and keeps the protofilaments in a straight conformation,
      resulting in a stable microtubule.

PMID- 18621814
TI  - Pressure effects on the ensemble dynamics of ubiquitin inspected with molecular
      dynamics simulations and isotropic reorientational eigenmode dynamics.
AB  - According to NMR chemical shift data, the ensemble of ubiquitin is a mixture of
      "open" and "closed" conformations at rapid equilibrium. Pressure perturbations
      provide the means to study the transition between the two conformers by imposing
      an additional constraint on the system's partial molar volume. Here we use
      nanosecond-timescale molecular dynamics simulations to characterize the network
      of correlated motions accessible to the conformers at low- and high-pressure
      conditions. Using the isotropic reorientational eigenmode dynamics formalism to
      analyze our simulation trajectories, we reproduce NMR relaxation data without
      fitting any parameters of our model. Comparative analysis of our results suggests
      that the two conformations behave very differently. The dynamics of the "closed"
      conformation are almost unaffected by pressure and are dominated by large
      amplitude correlated motions of residues 23-34 in the extended alpha-helix. The
      "open" conformation under conditions of normal pressure displays increased
      mobility, focused on the loop residues 17-20, 46-55, and 58-59 at the bottom of
      the core of the structure, as well as the C-terminal residues 69-76, that
      directly participate in key protein-protein interactions. For the same
      conformation, a pressure increase induces a loss of separability between
      molecular tumbling and internal dynamics, while motions between different
      backbone sites become uncorrelated.

PMID- 18621816
TI  - The surfactant peptide KL4 sequence is inserted with a transmembrane orientation
      into the endoplasmic reticulum membrane.
AB  - Surfactant protein B (SP-B) is an essential component of pulmonary surfactant.
      Synthetic surfactant peptide KL(4), a peptide based on a C-terminal amphipathic
      helical region of human SP-B, efficiently mimics some functional properties of SP
      B and is included in therapeutic surfactant preparations used in trials to treat
      respiratory distress syndrome. The membrane orientation of this peptide is
      controversial. We used an in vitro transcription-translation system to study the
      insertion of hydrophobic sequences into microsomal membranes, and showed that the
      KL(4) sequence integrates efficiently with a transmembrane orientation despite
      the presence of intermittent lysines throughout the sequence. In contrast, the
      precise sequence of the C-terminal SP-B amphipathic region failed to integrate,
      indicating a nontransmembrane orientation. Differences in the membrane insertion
      between KL(4) and the SP-B-inspiring sequence match predictions from calculated
      free energies of insertion of the two sequences into membranes.

PMID- 18621815
TI  - Characterizing complex dynamics in the transactivation response element apical
      loop and motional correlations with the bulge by NMR, molecular dynamics, and
      mutagenesis.
AB  - The HIV-1 transactivation response element (TAR) RNA binds a variety of proteins
      and is a target for developing anti-HIV therapies. TAR has two primary binding
      sites: a UCU bulge and a CUGGGA apical loop. We used NMR residual dipolar
      couplings, carbon spin relaxation (R(1) and R(2)), and relaxation dispersion
      (R(1rho)) in conjunction with molecular dynamics and mutagenesis to characterize
      the dynamics of the TAR apical loop and investigate previously proposed long
      range interactions with the distant bulge. Replacement of the wild-type apical
      loop with a UUCG loop did not significantly affect the structural dynamics at the
      bulge, indicating that the apical loop and the bulge act largely as independent
      dynamical recognition centers. The apical loop undergoes complex dynamics at
      multiple timescales that are likely important for adaptive recognition: U31 and
      G33 undergo limited motions, G32 is highly flexible at picosecond-nanosecond
      timescales, and G34 and C30 form a dynamic Watson-Crick basepair in which G34 and
      A35 undergo a slow (approximately 30 mus) likely concerted looping in and out
      motion, with A35 also undergoing large amplitude motions at picosecond-nanosecond
      timescales. Our study highlights the power of combining NMR, molecular dynamics,
      and mutagenesis in characterizing RNA dynamics.

PMID- 18621817
TI  - Metallic nanoparticles used to estimate the structural integrity of DNA motifs.
AB  - Branched DNA motifs can be designed to assume a variety of shapes and structures.
      These structures can be characterized by numerous solution techniques; the
      structures also can be inferred from atomic force microscopy of two-dimensional
      periodic arrays that the motifs form via cohesive interactions. Examples of these
      motifs are the DNA parallelogram, the bulged-junction DNA triangle, and the three
      dimensional-double crossover (3D-DX) DNA triangle. The ability of these motifs to
      withstand stresses without changing geometrical structure is clearly of interest
      if the motif is to be used in nanomechanical devices or to organize other large
      chemical species. Metallic nanoparticles can be attached to DNA motifs, and the
      arrangement of these particles can be established by transmission electron
      microscopy. We have attached 5 nm or 10 nm gold nanoparticles to every vertex of
      DNA parallelograms, to two or three vertices of 3D-DX DNA triangle motifs, and to
      every vertex of bulged-junction DNA triangles. We demonstrate by transmission
      electron microscopy that the DNA parallelogram motif and the bulged-junction DNA
      triangle are deformed by the presence of the gold nanoparticles, whereas the
      structure of the 3D-DX DNA triangle motif appears to be minimally distorted. This
      method provides a way to estimate the robustness and potential utility of the
      many new DNA motifs that are becoming available.

PMID- 18621818
TI  - Interplay of unsaturated phospholipids and cholesterol in membranes: effect of
      the double-bond position.
AB  - The structural and dynamical properties of lipid membranes rich in phospholipids
      and cholesterol are known to be strongly affected by the unsaturation of lipid
      acyl chains. We show that not only unsaturation but also the position of a double
      bond has a pronounced effect on membrane properties. We consider how cholesterol
      interacts with phosphatidylcholines comprising two 18-carbon long monounsaturated
      acyl chains, where the position of the double bond is varied systematically along
      the acyl chains. Atomistic molecular dynamics simulations indicate that when the
      double bond is not in contact with the cholesterol ring, and especially with the
      C18 group on its rough beta-side, the membrane properties are closest to those of
      the saturated bilayer. However, any interaction between the double bond and the
      ring promotes membrane disorder and fluidity. Maximal disorder is found when the
      double bond is located in the middle of a lipid acyl chain, the case most
      commonly found in monounsaturated acyl chains of phospholipids. The results
      suggest a cholesterol-mediated lipid selection mechanism in eukaryotic cell
      membranes. With saturated lipids, cholesterol promotes the formation of highly
      ordered raft-like membrane domains, whereas domains rich in unsaturated lipids
      with a double bond in the middle remain highly fluid despite the presence of
      cholesterol.

PMID- 18621819
TI  - Simulations of knotting in confined circular DNA.
AB  - The packing of DNA inside bacteriophages arguably yields the simplest example of
      genome organization in living organisms. As an assay of packing geometry, the DNA
      knot spectrum produced upon release of viral DNA from the P4 phage capsid has
      been analyzed, and compared to results of simulation of knots in confined
      volumes. We present new results from extensive stochastic sampling of confined
      self-avoiding and semiflexible circular chains with volume exclusion. The
      physical parameters of the chains (contour length, cross section, and bending
      rigidity) have been set to match those of P4 bacteriophage DNA. By using advanced
      sampling techniques, involving multiple Markov chain pressure-driven confinement
      combined with a thermodynamic reweighting technique, we establish the knot
      spectrum of the circular chains for increasing confinement up to the highest
      densities for which available algorithms can exactly classify the knots.
      Compactified configurations have an enclosing hull diameter approximately 2.5
      times larger than the P4 caliper size. The results are discussed in relation to
      the recent experiments on DNA knotting inside the capsid of a P4 tailless mutant.
      Our investigation indicates that confinement favors chiral knots over achiral
      ones, as found in the experiments. However, no significant bias of torus over
      twist knots is found, contrary to the P4 results. The result poses a crucial
      question for future studies of DNA packaging in P4: is the discrepancy due to the
      insufficient confinement of the equilibrium simulation or does it indicate that
      out-of-equilibrium mechanisms (such as rotation by packaging motors) affect the
      genome organization, hence its knot spectrum in P4?

PMID- 18621820
TI  - Interaction of gramicidin S and its aromatic amino-acid analog with phospholipid
      membranes.
AB  - To investigate the mechanism of interaction of gramicidin S-like antimicrobial
      peptides with biological membranes, a series of five decameric cyclic cationic
      beta-sheet-beta-turn peptides with all possible combinations of aromatic D-amino
      acids, Cyclo(Val-Lys-Leu-D-Ar1-Pro-Val-Lys-Leu-D-Ar2-Pro) (Ar identical with Phe,
      Tyr, Trp), were synthesized. Conformations of these cyclic peptides were
      comparable in aqueous solutions and lipid vesicles. Isothermal titration
      calorimetry measurements revealed entropy-driven binding of cyclic peptides to
      POPC and POPE/POPG lipid vesicles. Binding of peptides to both vesicle systems
      was endothermic-exceptions were peptides containing the Trp-Trp and Tyr-Trp pairs
      with exothermic binding to POPC vesicles. Application of one- and two-site
      binding (partitioning) models to binding isotherms of exothermic and endothermic
      binding processes, respectively, resulted in determination of peptide-lipid
      membrane binding constants (K(b)). The K(b1) and K(b2) values for endothermic two
      step binding processes corresponded to high and low binding affinities (K(b1)
      >or= 100 K(b2)). Conformational change of cyclic peptides in transferring from
      buffer to lipid bilayer surfaces was estimated using fluorescence resonance
      energy transfer between the Tyr-Trp pair in one of the peptide constructs. The
      cyclic peptide conformation expands upon adsorption on lipid bilayer surface and
      interacts more deeply with the outer monolayer causing bilayer deformation, which
      may lead to formation of nonspecific transient peptide-lipid porelike zones
      causing membrane lysis.

PMID- 18621821
TI  - Conformational changes in the selectivity filter of the open-state KcsA channel:
      an energy minimization study.
AB  - Potassium channels switch between closed and open conformations and selectively
      conduct K(+) ions. There are at least two gates. The TM2 bundle at the
      intracellular site is the primary gate of KcsA, and rearrangements at the
      selectivity filter (SF) act as the second gate. The SF blocks ion flow via an
      inactivation process similar to C-type inactivation of voltage-gated K(+)
      channels. We recently generated the open-state conformation of the KcsA channel.
      We found no major, possibly inactivating, structural changes in the SF associated
      with this massive inner-pore rearrangement, which suggests that the gates might
      act independently. Here we energy-minimize the open state of wild-type and mutant
      KcsA, validating in silico structures of energy-minimized SFs by comparison with
      crystallographic structures, and use these data to gain insight into how
      mutation, ion depletion, and K(+) to Na(+) substitution influence SF
      conformation. Both E71 or D80 protonations/mutations and the presence/absence of
      protein-buried water molecule(s) modify the H-bonding network stabilizing the P
      loops, spawning numerous SF conformations. We find that the inactivated state
      corresponds to conformations with a partially unoccupied or an entirely empty SF.
      These structures, involving modifications in all four P-loops, are stabilized by
      H-bonds between amide H and carbonyl O atoms from adjacent P-loops, which block
      ion passage. The inner portions of the P-loops are more rigid than the outer
      parts. Changes are localized to the outer binding sites, with innermost site S4
      persisting in the inactivated state. Strong binding by Na(+) locally contracts
      the SF around Na(+), releasing ligands that do not participate in Na(+)
      coordination, and occluding the permeation pathway. K(+) selectivity primarily
      appears to arise from the inability of the SF to completely dehydrate Na(+) ions
      due to basic structural differences between liquid water and the "quasi-liquid"
      SF matrix.

PMID- 18621822
TI  - Water-membrane partition thermodynamics of an amphiphilic lipopeptide: an
      enthalpy-driven hydrophobic effect.
AB  - To shed light on the driving force for the hydrophobic effect that partitions
      amphiphilic lipoproteins between water and membrane, we carried out an atomically
      detailed thermodynamic analysis of a triply lipid modified H-ras heptapeptide
      anchor (ANCH) in water and in a DMPC (1,2-dimyristoyl-sn-glycero-3
      phosphocholine) bilayer. Combining molecular mechanical and continuum solvent
      approaches with an improved technique for solute entropy calculation, we obtained
      an overall transfer free energy of approximately -13 kcal mol(-1). This value is
      in qualitative agreement with free energy changes derived from a potential of
      mean force calculation and indirect experimental observations. Changes in free
      energies of solvation and ANCH conformational reorganization are unfavorable,
      whereas ANCH-DMPC interactions-especially van der Waals-favor insertion. These
      results are consistent with an enthalpy-driven hydrophobic effect, in accord with
      earlier calorimetric data on the membrane partition of other amphiphiles.
      Furthermore, structural and entropic analysis of molecular dynamics-generated
      ensembles suggests that conformational selection may play a hitherto
      unappreciated role in membrane insertion of lipid-modified peptides and proteins.

PMID- 18621823
TI  - Charged surface area of maurocalcine determines its interaction with the skeletal
      ryanodine receptor.
AB  - The 33 amino acid scorpion toxin maurocalcine (MCa) has been shown to modify the
      gating of the skeletal-type ryanodine receptor (RyR1). Here we explored the
      effects of MCa and its mutants ([Ala(8)]MCa, [Ala(19)]MCa, [Ala(20)]MCa,
      [Ala(22)]MCa, [Ala(23)]MCa, and [Ala(24)]MCa) on RyR1 incorporated into
      artificial lipid bilayers and on elementary calcium release events (ECRE) in rat
      and frog skeletal muscle fibers. The peptides induced long-lasting subconductance
      states (LLSS) on RyR1 that lasted for several seconds. However, their average
      length and frequency were decreased if the mutation was placed farther away in
      the 3D structure from the critical (24)Arg residue. The effect was strongly
      dependent on the direction of the current through the channel. If the direction
      was similar to that followed by calcium during release, the peptides were 8- to
      10-fold less effective. In fibers long-lasting calcium release events were
      observed after the addition of the peptides. The average length of these events
      correlated well with the duration of LLSS. These data suggest that the effect of
      the peptide is governed by the large charged surface formed by residues Lys(20),
      Lys(22), Arg(23), Arg(24), and Lys(8). Our observations also indicate that the
      results from bilayer experiments mimic the in situ effects of MCa on RyR1.

PMID- 18621824
TI  - A new FRAP/FRAPa method for three-dimensional diffusion measurements based on
      multiphoton excitation microscopy.
AB  - We present a new convenient method for quantitative three-dimensionally resolved
      diffusion measurements based on the photobleaching (FRAP) or photoactivation
      (FRAPa) of a disk-shaped area by the scanning laser beam of a multiphoton
      microscope. Contrary to previously reported spot-photobleaching protocols, this
      method has the advantage of full scalability of the size of the photobleached
      area and thus the range of diffusion coefficients, which can be measured
      conveniently. The method is compatible with low as well as high numerical
      aperture objective lenses, allowing us to perform quantitative diffusion
      measurements in three-dimensional extended samples as well as in very small
      volumes, such as cell nuclei. Furthermore, by photobleaching/photoactivating a
      large area, diffusion along the optical axis can be measured separately, which is
      convenient when studying anisotropic diffusion. First, we show the rigorous
      mathematical derivation of the model, leading to a closed-form formula describing
      the fluorescence recovery/redistribution phase. Next, the ability of the
      multiphoton FRAP method to correctly measure absolute diffusion coefficients is
      tested thoroughly on many test solutions of FITC-dextrans covering a wide range
      of diffusion coefficients. The same is done for the FRAPa method on a series of
      photoactivatable green fluorescent protein solutions with different viscosities.
      Finally, we apply the method to photoactivatable green fluorescent protein
      diffusing freely in the nucleus of living NIH-3T3 mouse embryo fibroblasts.

PMID- 18621825
TI  - Polymerization and bundling kinetics of FtsZ filaments.
AB  - FtsZ is a tubulin homolog essential for prokaryotic cell division. In living
      bacteria, FtsZ forms a ringlike structure (Z-ring) at the cell midpoint. Cell
      division coincides with a gradual contraction of the Z-ring, although the
      detailed molecular structure of the Z-ring is unknown. To reveal the structural
      properties of FtsZ, an understanding of FtsZ filament and bundle formation is
      needed. We develop a kinetic model that describes the polymerization and bundling
      mechanism of FtsZ filaments. The model reveals the energetics of the FtsZ
      filament formation and the bundling energy between filaments. A weak lateral
      interaction between filaments is predicted by the model. The model is able to fit
      the in vitro polymerization kinetics data of another researcher, and explains the
      cooperativity observed in FtsZ kinetics and the critical concentration in
      different buffer media. The developed model is also applicable for understanding
      the kinetics and energetics of other bundling biopolymer filaments.

PMID- 18621826
TI  - Intracellular calcium release channels mediate their own countercurrent: the
      ryanodine receptor case study.
AB  - Intracellular calcium release channels like ryanodine receptors (RyRs) and
      inositol trisphosphate receptors (IP(3)Rs) mediate large Ca(2+) release events
      from Ca(2+) storage organelles lasting >5 ms. To have such long-lasting Ca(2+)
      efflux, a countercurrent of other ions is necessary to prevent the membrane
      potential from becoming the Ca(2+) Nernst potential in <1 ms. A recent model of
      ion permeation through a single, open RyR channel is used here to show that the
      vast majority of this countercurrent is conducted by the RyR itself.
      Consequently, changes in membrane potential are minimized locally and instantly,
      assuring maintenance of a Ca(2+)-driving force. This RyR autocountercurrent is
      possible because of the poor Ca(2+) selectivity and high conductance for both
      monovalent and divalent cations of these channels. The model shows that, under
      physiological conditions, the autocountercurrent clamps the membrane potential
      near 0 mV within approximately 150 mus. Consistent with experiments, the model
      shows how RyR unit Ca(2+) current is defined by luminal [Ca(2+)], permeable ion
      composition and concentration, and pore selectivity and conductance. This very
      likely is true of the highly homologous pore of the IP(3)R channel.

PMID- 18621827
TI  - Role of extracellular glutamic acids in the stability and energy landscape of
      bacteriorhodopsin.
AB  - Bacteriorhodopsin (BR), a specialized nanomachine, converts light energy into a
      proton gradient to power Halobacterium salinarum. In this work, we analyze the
      mechanical stability of a BR triple mutant in which three key extracellular
      residues, Glu(9), Glu(194), and Glu(204), were mutated simultaneously to Gln.
      These three Glu residues are involved in a network of hydrogen bonds, in cation
      binding, and form part of the proton release pathway of BR. Changes in these
      features and the robust photocycle dynamics of wild-type (WT) BR are apparent
      when the three extracellular Glu residues are mutated to Gln. It is speculated
      that such functional changes of proteins go hand in hand with changes in their
      mechanical properties. Here, we apply single-molecule dynamic force spectroscopy
      to investigate how the Glu to Gln mutations change interactions, reaction
      pathways, and the energy barriers of the structural regions of WT BR. The altered
      heights and positions of individual energy barriers unravel the changes in the
      mechanical and the unfolding kinetic properties of the secondary structures of WT
      BR. These changes in the mechanical unfolding energy landscape cause the proton
      pump to choose unfolding pathways differently. We suggest that, in a similar
      manner, the changed mechanical properties of mutated BR alter the functional
      energy landscape favoring different reaction pathways in the light-induced proton
      pumping mechanism.

PMID- 18621828
TI  - Protein-protein interaction investigated by steered molecular dynamics: the TCR
      pMHC complex.
AB  - We present a novel steered molecular dynamics scheme to induce the dissociation
      of large protein-protein complexes. We apply this scheme to study the interaction
      of a T cell receptor (TCR) with a major histocompatibility complex (MHC)
      presenting a peptide (p). Two TCR-pMHC complexes are considered, which only
      differ by the mutation of a single amino acid on the peptide; one is a strong
      agonist that produces T cell activation in vivo, while the other is an
      antagonist. We investigate the interaction mechanism from a large number of
      unbinding trajectories by analyzing van der Waals and electrostatic interactions
      and by computing energy changes in proteins and solvent. In addition,
      dissociation potentials of mean force are calculated with the Jarzynski identity,
      using an averaging method developed for our steering scheme. We analyze the
      convergence of the Jarzynski exponential average, which is hampered by the large
      amount of dissipative work involved and the complexity of the system. The
      resulting dissociation free energies largely underestimate experimental values,
      but the simulations are able to clearly differentiate between wild-type and
      mutated TCR-pMHC and give insights into the dissociation mechanism.

PMID- 18621829
TI  - Molecular modeling of the axial and circumferential elastic moduli of tubulin.
AB  - Microtubules play a number of important mechanical roles in almost all cell types
      in nearly all major phylogenetic trees. We have used a molecular mechanics
      approach to perform tensile tests on individual tubulin monomers and determined
      values for the axial and circumferential moduli for all currently known complete
      sequences. The axial elastic moduli, in vacuo, were found to be 1.25 GPa and 1.34
      GPa for alpha- and beta-bovine tubulin monomers. In the circumferential
      direction, these moduli were 378 MPa for alpha- and 460 MPa for beta-structures.
      Using bovine tubulin as a template, 269 homologous tubulin structures were also
      subjected to simulated tensile loads yielding an average axial elastic modulus of
      1.10 +/- 0.14 GPa for alpha-tubulin structures and 1.39 +/- 0.68 GPa for beta
      tubulin. Circumferentially the alpha- and beta-moduli were 936 +/- 216 MPa and
      658 +/- 134 MPa, respectively. Our primary finding is that that the axial elastic
      modulus of tubulin diminishes as the length of the monomer increases. However, in
      the circumferential direction, no correlation exists. These predicted
      anisotropies and scale dependencies may assist in interpreting the macroscale
      behavior of microtubules during mitosis or cell growth. Additionally, an
      intergenomic approach to investigating the mechanical properties of proteins may
      provide a way to elucidate the evolutionary mechanical constraints imposed by
      nature upon individual subcellular components.

PMID- 18621830
TI  - Peptide aggregation in finite systems.
AB  - Universal features of the peptide aggregation process suggest a common mechanism,
      with a first-order phase transition in aqueous solutions of the peptides being
      the driving force. Small system sizes strongly affect the stability of the minor
      phase in the two-phase region. We show manifestations of this effect in aqueous
      solutions of fragments of the islet amyloid polypeptide, using computer
      simulation methods and invoking various approaches in characterizing clustering
      and aggregate formation. These systems with peptide concentrations deeply inside
      the immiscibility region show two distinct stable states, which interchange with
      time: one state contains a peptide aggregate; and the other state has an
      aggregate that is noticeably dissolved. The first state is relevant for
      macroscopic systems, whereas the second one is artificial. At a fixed
      concentration, the occurrence probability of the aggregate state vanishes upon
      decreasing the system size, thus indicating the necessity to apply a finite size
      scaling for meaningful studies of peptide aggregation by simulations. The effect
      observed may be one of the factors responsible for the difference between
      intracellular and extracellular aggregation and fibrillization of polypeptides.
      The finite size of biological cells or their compartments may be playing a
      decisive role in hampering intracellular aggregation of highly insoluble
      amyloidogenic proteins, whereas aggregation is unavoidable in the extracellular
      space at the same peptide concentration.

PMID- 18621831
TI  - Influence of nonuniform geometry on nanoindentation of viral capsids.
AB  - A series of recent nanoindentation experiments on the protein shells (capsids) of
      viruses has established atomic force microscopy (AFM) as a useful framework for
      probing the mechanics of large protein assemblies. Specifically these experiments
      provide an opportunity to study the coupling of the global assembly response to
      local conformational changes. AFM experiments on cowpea chlorotic mottle virus,
      known to undergo a pH-controlled swelling conformational change, have revealed a
      pH-dependent mechanical response. Previous theoretical studies have shown that
      homogeneous changes in shell geometry can play a significant role in the
      mechanical response. This article develops a method for accurately capturing the
      heterogeneous geometry of a viral capsid and explores its effect on mechanical
      response with a nonlinear continuum elasticity model. Models of both native and
      swollen cowpea chlorotic mottle virus capsids are generated from x-ray crystal
      structures, and are used in finite element simulations of AFM indentation along
      two-, three-, and fivefold icosahedral symmetry orientations. The force response
      of the swollen capsid model is observed to be softer by roughly a factor of two,
      significantly more nonlinear, and more orientation-dependent than that of a
      native capsid with equivalent elastic moduli, demonstrating that capsid geometric
      heterogeneity can have significant effects on the global structural response.

PMID- 18621832
TI  - Conformation and membrane orientation of amphiphilic helical peptides by oriented
      circular dichroism.
AB  - Oriented circular dichroism (OCD) was used to characterize and compare in a
      quantitative manner the secondary structure and concentration dependent
      realignment of the antimicrobial peptides PGLa and MSI-103, and of the
      structurally related cell-penetrating peptide MAP in aligned phospholipid
      bilayers. All these peptides adopt an amphiphilic alpha-helical conformation, and
      from solid-state NMR analysis they are known to bind to membranes in two distinct
      orientations depending on their concentration. At low peptide/lipid (P/L) ratio
      the helices are aligned parallel to membrane surface (S-state), but with
      increasing concentration they realign to a tilted orientation (T-state), getting
      immersed into the membrane with an oblique angle supposedly as a result of dimer
      formation. In macroscopically aligned liquid crystalline 1,2-dimyristoyl-sn
      glycero-3-phosphatidylcholine bilayers the two limiting states are represented by
      distinct OCD spectra, and all spectra at intermediate peptide concentrations can
      be described by a linear combination of these two line shapes. The corresponding
      fraction of molecules occupying the T-state was determined by fitting the
      intermediate spectra with a superposition of the two extreme line shapes. By
      plotting this fraction versus 1/(P/L), the threshold P/L* ratio for realignment
      was extracted for each of the three related peptides. Despite their structural
      similarity distinctly different thresholds were obtained, namely for MSI-103
      realignment starts already at a low P/L of approximately 1:236, for a MAP
      derivative (using a nonaggregating analog containing a D-amino acid) the
      transition begins at P/L approximately 1:156, whereas PGLa needs the highest
      concentration to flip into T-state at P/L approximately 1:85. Analysis of the
      original MAP sequence (containing only L-amino acids) gave OCD spectra compatible
      with beta-pleated conformation, suggesting that this peptide starts to aggregate
      with increasing concentration, unlike the other helical peptides. All these
      changes in peptide conformation and membrane alignment observed here by OCD seem
      to be functionally relevant, as they can be correlated with the membrane
      perturbing activities of the three antimicrobial and cell-penetrating sequences.

PMID- 18621833
TI  - Scaling theory of polymer translocation into confined regions.
AB  - We examine the voltage-driven polymer translocation from a spacious region into a
      confined region imposed by two parallel planes, so that the entry is impeded by
      the entropic confinement but aided by the electric field inside the confined
      region. Two modes of entry are examined: linear translocation where a chain
      enters the confined region with chain ends, and hairpin translocation where a
      chain enters the confined region by forming a hairpin. Our calculation shows that
      translocation time increases with polymer length for linear entries but decreases
      with polymer length for hairpin entries. Applying to electrophoresis of DNA
      molecules through periodic spacious and confined regions, our theory shows that
      the dominance of hairpin translocations leads to the experimentally observed
      faster migration of longer DNA molecules. Our theory predicts experimental
      conditions for the validity of this law in terms of polymer length, size of the
      confined region, and solution conditions.

PMID- 18621834
TI  - Generation, comparison, and merging of pathways between protein conformations:
      gating in K-channels.
AB  - We present a general framework for the generation, alignment, comparison, and
      hybridization of motion pathways between two known protein conformations. The
      framework, which is rooted in probabilistic motion-planning techniques in
      robotics, allows for the efficient generation of collision-free motion pathways,
      while considering a wide range of degrees of freedom involved in the motion.
      Within the framework, we provide the means to hybridize pathways, thus producing,
      the motion pathway of the lowest energy barrier out of the many pathways proposed
      by our algorithm. This method for comparing and hybridizing pathways is modular,
      and may be used within the context of molecular dynamics and Monte Carlo
      simulations. The framework was implemented within the Rosetta software suite,
      where the protein is represented in atomic detail. The K-channels switch between
      open and closed conformations, and we used the overall framework to investigate
      this transition. Our analysis suggests that channel-opening may follow a three
      phase pathway. First, the channel unlocks itself from the closed state; second,
      it opens; and third, it locks itself in the open conformation. A movie that
      depicts the proposed pathway is available in the Supplementary Material (Movie
      S1) and at http://www.cs.tau.ac.il/~angela/SuppKcsA.html.

PMID- 18621835
TI  - Mechanical stability of helical beta-peptides and a comparison of explicit and
      implicit solvent models.
AB  - Synthetic beta-peptide oligomers have been shown to form stable folded structures
      analogous to those encountered in naturally occurring proteins. Literature
      studies have speculated that the conformational stability of beta-peptides is
      greater than that of alpha-peptides. Direct measurements of that stability,
      however, are not available. Molecular simulations are used in this work to
      quantify the mechanical stability of four helical beta-peptides. This is achieved
      by subjecting the molecules to tension. The potential of mean force associated
      with the resulting unfolding process is determined using both an implicit and an
      explicit solvent model. It is found that all four molecules exhibit a highly
      stable helical structure. It is also found that the energetic contributions to
      the potential of mean force do not change appreciably when the molecules are
      stretched in explicit water. In contrast, the entropic contributions decrease
      significantly. As the peptides unfold, a loss of intramolecular energy is
      compensated by the formation of additional water-peptide hydrogen bonds. These
      entropic effects lead in some cases to a loss of stability upon cooling the
      peptides, a phenomenon akin to the cold denaturing of some proteins. While the
      location of the free energy minimum and the structural helicity of the peptides
      are comparable in the implicit-solvent and explicit-water cases, it is found
      that, in general, the helical structure of the molecules is more stable in the
      implicit solvent model than in explicit water.

PMID- 18621836
TI  - Monovalent and divalent promoted GAAA tetraloop-receptor tertiary interactions
      from freely diffusing single-molecule studies.
AB  - Proper assembly of RNA into catalytically active three-dimensional structures
      requires multiple tertiary binding interactions, individual characterization of
      which is crucial to a detailed understanding of global RNA folding. This work
      focuses on single-molecule fluorescence studies of freely diffusing RNA
      constructs that isolate the GAAA tetraloop-receptor tertiary interaction. Freely
      diffusing conformational dynamics are explored as a function of Mg(2+) and Na(+)
      concentration, both of which promote facile docking, but with 500-fold different
      affinities. Systematic shifts in mean fluorescence resonance energy transfer
      efficiency values and line widths with increasing [Na(+)] are observed for the
      undocked species and can be interpreted with a Debye model in terms of
      electrostatic relaxation and increased flexibility in the RNA. Furthermore, we
      identify a 34 +/- 2% fraction of freely diffusing RNA constructs remaining
      undocked even at saturating [Mg(2+)] levels, which agrees quantitatively with the
      32 +/- 1% fraction previously reported for immobilized constructs. This verifies
      that the kinetic heterogeneity observed in the docking rates is not the result of
      surface tethering. Finally, the K(D) value and Hill coefficient for [Mg(2+)]
      dependent docking decrease significantly for [Na(+)] = 25 mM vs. 125 mM,
      indicating Mg(2+) and Na(+) synergy in the RNA folding process.

PMID- 18621837
TI  - Control of transcriptional variability by overlapping feed-forward regulatory
      motifs.
AB  - In yeast, beta-oxidation of fatty acids (FAs) takes place in the peroxisome, an
      organelle whose size and number are controlled in response to environmental cues.
      The expression of genes required for peroxisome assembly and function is
      controlled by a transcriptional regulatory network that is induced by FAs such as
      oleate. The core FA-responsive transcriptional network consists of carbon source
      sensing transcription factors that regulate key target genes through an
      overlapping feed-forward network motif (OFFNM). However, a systems-level
      understanding of the function of this network architecture in regulating dynamic
      FA-induced gene expression is lacking. The specific role of the OFFNM in
      regulating the dynamic and cell-population transcriptional response to oleate was
      investigated using a kinetic model comprised of four core transcription factor
      genes (ADR1, OAF1, PIP2, and OAF3) and two reporter genes (CTA1 and POT1) that
      are indicative of peroxisome induction. Simulations of the model suggest that 1),
      the intrinsic Adr1p-driven feed-forward loop reduces the steady-state expression
      variability of target genes; 2), the parallel Oaf3p-driven inhibitory feed
      forward loop modulates the dynamic response of target genes to a transiently
      varying oleate concentration; and 3), heterodimerization of Oaf1p and Pip2p does
      not appear to have a noise-reducing function in the context of oleate-dependent
      expression of target genes. The OFFNM is highly overrepresented in the yeast
      regulome, suggesting that the specific functions described for the OFFNM, or
      other properties of this motif, provide a selective advantage.

PMID- 18621838
TI  - Modeling subunit cooperativity in opening of tetrameric ion channels.
AB  - Most potassium channels are tetramers of four homologous polypeptides (subunits).
      During channel gating, each subunit undergoes several conformational changes
      independent of the state of other subunits before reaching a permissive state,
      from which the channel can open. However, transition from the permissive states
      to the open state involves a concerted movement of all subunits. This cooperative
      transition must be included in Markov models of channel gating. Previously, it
      was implemented by considering all possible combinations of four subunit states
      in a much larger expanded model of channel states (e.g., 27,405 channel states
      versus 64 subunit states), which complicates modeling and is computationally
      intense, especially when accurate modeling requires a large number of subunit
      states. To overcome these complexities and retain the tetrameric molecular
      structure, a modeling approach was developed to incorporate the cooperative
      transition directly from the subunit models. In this approach, the open state is
      separated from the subunit models and represented by the net flux between the
      open state and the permissive states. Dynamic variations of the probability of
      state residencies computed using this direct approach and the expanded model were
      identical. Implementation of the direct approach is simple and its computational
      time is orders-of-magnitude shorter than the equivalent expanded model.

PMID- 18621839
TI  - Orientation of the essential light chain region of myosin in relaxed, active, and
      rigor muscle.
AB  - The orientation of the ELC region of myosin in skeletal muscle was determined by
      polarized fluorescence from ELC mutants in which pairs of introduced cysteines
      were cross-linked by BSR. The purified ELC-BSRs were exchanged for native ELC in
      demembranated fibers from rabbit psoas muscle using a trifluoperazine-based
      protocol that preserved fiber function. In the absence of MgATP (in rigor) the
      ELC orientation distribution was narrow; in terms of crystallographic structures
      of the myosin head, the LCD long axis linking heavy-chain residues 707 and 843
      makes an angle (beta) of 120-125 degrees with the filament axis. This is
      approximately 30 degrees larger than the broader distribution determined
      previously from RLC probes, suggesting that, relative to crystallographic
      structures, the LCD is bent between its ELC and RLC regions in rigor muscle. The
      ELC orientation distribution in relaxed muscle had two broad peaks with beta
      approximately 70 degrees and approximately 110 degrees, which may correspond to
      the two head regions of each myosin molecule, in contrast with the single broad
      distribution of the RLC region in relaxed muscle. During isometric contraction
      the ELC orientation distribution peaked at beta approximately 105 degrees ,
      similar to that determined previously for the RLC region.

PMID- 18621840
TI  - Lipid bilayer deformation and the free energy of interaction of a Kv channel
      gating-modifier toxin.
AB  - A number of membrane proteins act via binding at the water/lipid bilayer
      interface. An important example of such proteins is provided by the gating
      modifier toxins that act on voltage-gated potassium (Kv) channels. They are
      thought to partition to the headgroup region of lipid bilayers, and so provide a
      good system for probing the nature of interactions of a protein with the
      water/bilayer interface. We used coarse-grained molecular dynamics simulations to
      compute the one-dimensional potential of mean force (i.e., free energy) profile
      that governs the interaction between a Kv channel gating-modifier toxin (VSTx1)
      and model phospholipid bilayers. The reaction coordinate sampled corresponds to
      the position of the toxin along the bilayer normal. The course-grained
      representation of the protein and lipids enabled us to explore extended time
      periods, revealing aspects of toxin/bilayer dynamics and energetics that would be
      difficult to observe on the timescales currently afforded by atomistic molecular
      dynamics simulations. In particular, we show for this model system that the
      bilayer deforms as it interacts with the toxin, and that such deformations
      perturb the free energy profile. Bilayer deformation therefore adds an additional
      layer of complexity to be addressed in investigations of membrane/protein
      systems. In particular, one should allow for local deformations that may arise
      due to the spatial array of charged and hydrophobic elements of an interfacially
      located membrane protein.

PMID- 18621841
TI  - Phase separation and crystallization of hemoglobin C in transgenic mouse and
      human erythrocytes.
AB  - Individuals expressing hemoglobin C (beta6 Glu-->Lys) present red blood cells
      (RBC) with intraerythrocytic crystals that form when hemoglobin (Hb) is
      oxygenated. Our earlier in vitro liquid-liquid (L-L) phase separation studies
      demonstrated that liganded HbC exhibits a stronger net intermolecular attraction
      with a longer range than liganded HbS or HbA, and that L-L phase separation
      preceded and enhanced crystallization. We now present evidence for the role of
      phase separation in HbC crystallization in the RBC, and the role of the RBC
      membrane as a nucleation center. RBC obtained from both human homozygous HbC
      patients and transgenic mice expressing only human HbC were studied by bright
      field and differential interference contrast video-enhanced microscopy. RBC were
      exposed to hypertonic NaCl solution (1.5-3%) to induce crystallization within an
      appropriate experimental time frame. L-L phase separation occurred inside the
      RBC, which in turn enhanced the formation of intraerythrocytic crystals. RBC L-L
      phase separation and crystallization comply with the thermodynamic and kinetics
      laws established through in vitro studies of phase transformations. This is the
      first report, to the best of our knowledge, to capture a temporal view of
      intraerythrocytic HbC phase separation, crystal formation, and dissolution.

PMID- 18621842
TI  - Dynamics of voltage profile in enzymatic ion transporters, demonstrated in
      electrokinetics of proton pumping rhodopsin.
AB  - H(+)-pumping rhodopsins mediate a primordial conversion of light to metabolic
      energy. Bacteriorhodopsin from Halobacterium salinarium is the first identified
      and (biochemically) best-studied H(+)-pumping rhodopsin. The electrical
      properties of H(+)-pumping rhodopsins, however, are known in more detail for the
      homolog Acetabularia rhodopsin, isolated from the eukaryotic green alga
      Acetabularia acetabulum. Based on data from Acetabularia rhodopsin we present a
      general reaction kinetic model of H(+)-pumping rhodopsins with only seven
      independent parameters, which fits the kinetic properties of photocurrents as
      functions of light, transmembrane voltage, internal and external pH, and time.
      The model describes fast photoisomerization of retinal with simultaneous H(+)
      transfer to an H(+) acceptor, reprotonation of retinal from the intracellular
      face via an H(+) donor, and proton release to the extracellular space via an H(+)
      release complex. The voltage sensitivities of the individual reaction steps and
      their temporal changes are treated here by a novel approach, whereby--as in an
      Ohmic voltage divider--the effective portions of the total transmembrane voltage
      decrease with the relative velocities of the individual reaction steps. This
      analysis quantitatively infers dynamic changes of the voltage profile and of the
      pK values of the H(+)-binding sites involved.

PMID- 18621844
TI  - Comment to the article by Michael J. Saxton: A biological interpretation of
      transient anomalous subdiffusion. I. qualitative model.

PMID- 18621845
TI  - Modeling the establishment of PAR protein polarity in the one-cell C. elegans
      embryo.
AB  - At the one-cell stage, the C. elegans embryo becomes polarized along the anterior
      posterior axis. The PAR proteins form complementary anterior and posterior
      domains in a dynamic process driven by cytoskeletal rearrangement. Initially, the
      PAR proteins are uniformly distributed throughout the embryo. After a cue from
      fertilization, cortical actomyosin contracts toward the anterior pole. PAR-3/PAR
      6/PKC-3 (the anterior PAR proteins) become restricted to the anterior cortex. PAR
      1 and PAR-2 (the posterior PAR proteins) become enriched in the posterior
      cortical region. We present a mathematical model of this polarity establishment
      process, in which we take a novel approach to combine reaction-diffusion dynamics
      of the PAR proteins coupled to a simple model of actomyosin contraction. We show
      that known interactions between the PAR proteins are sufficient to explain many
      aspects of the observed cortical PAR dynamics in both wild-type and mutant
      embryos. However, cytoplasmic PAR protein polarity, which is vital for generating
      daughter cells with distinct molecular components, cannot be properly explained
      within such a framework. We therefore consider additional mechanisms that can
      reproduce the proper cytoplasmic polarity. In particular we predict that
      cytoskeletal asymmetry in the cytoplasm, in addition to the cortical actomyosin
      asymmetry, is a critical determinant of PAR protein localization.

PMID- 18621846
TI  - How topological constraints facilitate growth and stability of bubbles in DNA.
AB  - The bubbles in double-stranded DNA, essential for gene transcription and
      replication, occur in mechanically constrained situations. Through an elastic
      model incorporating topological constraint, we show that, when a stretched double
      helix is underwound above a critical value of twist, a bubble can spontaneously
      form, yielding extension and torque behaviors quantitatively in agreement with
      magnetic tweezers experiments. We find that, unlike thermal bubble in an
      unconstrained DNA, the bubbles in these constrained states can grow and
      stabilize, provided that tension and length of DNA are above critical values.

PMID- 18621847
TI  - A prospective longitudinal study comparing a radical retropubic prostatectomy and
      permanent prostate brachytherapy regarding the health-related quality of life for
      localized prostate cancer.
AB  - OBJECTIVE: The health-related quality of life (HRQOL) after a radical retropubic
      prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) was prospectively
      compared at a single institute. METHODS: Between 2003 and 2005, 122 patients were
      treated by RRP and 82 patients were treated by PPB. A QOL survey was completed at
      baseline, and 1, 3, 6 and 12 months after treatment, prospectively. RESULTS: The
      general HRQOL was not different between the RRP and PPB groups after 3 months.
      However, at 1 month after treatment, the general HRQOL scores, except for general
      health, were significantly better in the PPB group than that in the RRP group.
      Moreover, the disease-specific QOL was worse in urinary and sexual functions in
      the RRP group. Urinary function in the RRP group had not recovered to baseline
      after 12 months. Although the urinary function in the PPB group was better than
      that of the RRP group, urinary bother continued to worsen until 6 months and
      thereafter it recovered gradually. The bowel function was not worse in the PPB
      group but bowel bother was worse at 6 months in the PPB group. In the RRP group,
      the patients with nerve sparing demonstrated better in sexual function than those
      without nerve sparing, but the recovery did not reach the level of the PPB group.
      CONCLUSIONS: This prospective study revealed the differences in the QOL after RRP
      and PPB. These results will be helpful for making treatment decisions.

PMID- 18621848
TI  - Comparison of the outcome and morbidity for localized or locally advanced
      prostate cancer treated by high-dose-rate brachytherapy plus external beam
      radiotherapy (EBRT) versus EBRT alone.
AB  - OBJECTIVE: To compare the survival, gastrointestinal (GI) and genitourinary (GU)
      toxicity for localized or locally advanced prostate cancer treated by high-dose
      rate-brachytherapy (HDR-BT) plus external beam radiotherapy (EBRT) versus EBRT
      alone at a single institute in Taiwan. METHODS: Eighty-eight patients with T1c
      T3b prostate cancer consecutively treated by EBRT alone (33 patients) or HDR
      BT+EBRT (55 patients) were studied. The median dose of EBRT was 70.2 Gy in the
      EBRT group and 50.4 Gy in the HDR-BT group. HDR-BT was performed 2-3 weeks before
      EBRT, with 12.6 Gy in three fractions over 24 h. RESULTS: Five patients (15.2%)
      in the EBRT group and seven (12.7%) in the HDR-BT group developed a biochemical
      relapse. The 5-year actuarial biochemical relapse-free survival rates were 65.0%
      in the EBRT group and 66.7% in the HDR-BT group (P = 0.76). The 5-year actuarial
      likelihood of late > or =Grade 2 and > or =Grade 3 GI toxicity in the EBRT versus
      HDR-BT group was 62.8 versus 7.7% (P < 0.001) and 19.6 versus 0% (P = 0.001),
      respectively. In a multivariate analysis, the only predictor for late GI toxicity
      was the mode of RT. The 5-year actuarial likelihood of late > or =Grade 2 and >
      or =Grade 3 GU toxicity in the EBRT versus HDR-BT group was 14.8 versus 15.9% (P
      = 0.86) and 3.6 versus 8.5% (P = 0.40), respectively. CONCLUSIONS: The addition
      of HDR-BT before EBRT with a reduced dose from the EBRT produces a comparable
      survival outcome and GU toxicity but a significantly less GI toxicity for
      prostate cancer patients.

PMID- 18621849
TI  - Inhibition of vascular smooth muscle cell proliferation by chronic hemin
      treatment.
AB  - Hemin, an oxidized form of heme, is an essential regulator of gene expression and
      cell cycle progression. Our laboratory previously reported (34) that chronic
      hemin treatment of spontaneously hypertensive rats reversed the eutrophic inward
      remodeling of small peripheral arteries. Whether long-term treatment of cultured
      vascular smooth muscle cells (VSMCs) with hemin alters the proliferation status
      of these cells has been unknown. In the present study, hemin treatment at 5 muM
      for 4, 7, 14, and 21 days significantly inhibited the proliferation of cultured
      rat aortic VSMCs (A-10 cells) by arresting cells at G0/G1 phases so as to
      decelerate cell cycle progression. Heme oxygenase (HO) activity and inducible HO
      1 protein expression were significantly increased by hemin treatment. HO
      inhibitor tin protoporphyrin IX (SnPP) abolished the effects of hemin on cell
      proliferation and HO activity. Interestingly, hemin-induced HO-1 expression was
      further increased in the presence of SnPP. Hemin treatment had no significant
      effect on the expression of constitutive HO-2. Expression of p21 protein and the
      level of reactive oxygen species (ROS) were decreased by hemin treatment, which
      was reversed by application of SnPP. After removal of hemin from culture medium,
      inhibited cell proliferation and increased HO-1 expression in VSMCs were returned
      to control level within 1 wk. Transfection with HO-1 small interfering RNA
      significantly knocked down HO-1 expression and decreased HO activity, but had no
      effect on HO-2 expression, in cells treated with or without hemin for 7 days. The
      inhibitory effect of hemin on cell proliferation was abolished in HO-1 silenced
      cells. It is concluded that induction of HO-1 and, consequently, increased HO
      activity are responsible for the chronic inhibitory effect of hemin on VSMC
      proliferation. Changes in the levels of p21 and ROS might also participate in the
      cellular effects of hemin.

PMID- 18621850
TI  - Toward a noninvasive subject-specific estimation of abdominal aortic pressure.
AB  - A method for estimation of central arterial pressure based on linear one
      dimensional wave propagation theory is presented in this paper. The equations are
      applied to a distributed model of the arterial tree, truncated by three-element
      windkessels. To reflect individual differences in the properties of the arterial
      trees, we pose a minimization problem from which individual parameters are
      identified. The idea is to take a measured waveform in a peripheral artery and
      use it as input to the model. The model subsequently predicts the corresponding
      waveform in another peripheral artery in which a measurement has also been made,
      and the arterial tree model is then calibrated in such a way that the computed
      waveform matches its measured counterpart. For the purpose of validation,
      invasively recorded abdominal aortic, brachial, and femoral pressures in nine
      healthy subjects are used. The results show that the proposed method estimates
      the abdominal aortic pressure wave with good accuracy. The root mean square error
      (RMSE) of the estimated waveforms was 1.61 +/- 0.73 mmHg, whereas the errors in
      systolic and pulse pressure were 2.32 +/- 1.74 and 3.73 +/- 2.04 mmHg,
      respectively. These results are compared with another recently proposed method
      based on a signal processing technique, and it is shown that our method yields a
      significantly (P < 0.01) lower RMSE. With more extensive validation, the method
      may eventually be used in clinical practice to provide detailed, almost
      individual, specific information as a valuable basis for decision making.

PMID- 18621851
TI  - Strain distribution over plaques in human coronary arteries relates to shear
      stress.
AB  - Once plaques intrude into the lumen, the shear stress they are exposed to alters
      with hitherto unknown consequences for plaque composition. We investigated the
      relationship between shear stress and strain, a marker for plaque composition, in
      human coronary arteries. We imaged 31 plaques in coronary arteries with
      angiography and intravascular ultrasound. Computational fluid dynamics was used
      to obtain shear stress. Palpography was applied to measure strain. Each plaque
      was divided into four regions: upstream, throat, shoulder, and downstream.
      Average shear stress and strain were determined in each region. Shear stress in
      the upstream, shoulder, throat, and downstream region was 2.55+/-0.89, 2.07+/
      0.98, 2.32+/-1.11, and 0.67+/-0.35 Pa, respectively. Shear stress in the
      downstream region was significantly lower. Strain in the downstream region was
      also significantly lower than the values in the other regions (0.23+/-0.08% vs.
      0.48+/-0.15%, 0.43+/-0.17%, and 0.47+/-0.12%, for the upstream, shoulder, and
      throat regions, respectively). Pooling all regions, dividing shear stress per
      plaque into tertiles, and computing average strain showed a positive correlation;
      for low, medium, and high shear stress, strain was 0.23+/-0.10%, 0.40+/-0.15%,
      and 0.60+/-0.18%, respectively. Low strain colocalizes with low shear stress
      downstream of plaques. Higher strain can be found in all other plaque regions,
      with the highest strain found in regions exposed to the highest shear stresses.
      This indicates that high shear stress might destabilize plaques, which could lead
      to plaque rupture.

PMID- 18621852
TI  - The metabolic basis of vascular oxygen sensing: diversity, compartmentalization,
      and lessons from cancer.

PMID- 18621853
TI  - Conditioning the heart induces formation of signalosomes that interact with
      mitochondria to open mitoKATP channels.
AB  - Perfusion of the heart with bradykinin triggers cellular signaling events that
      ultimately cause opening of mitochondrial ATP-sensitive K+ (mitoKATP) channels,
      increased H2O2 production, inhibition of the mitochondrial permeability
      transition (MPT), and cardioprotection. We hypothesized that the interaction of
      bradykinin with its receptor induces the assembly of a caveolar signaling
      platform (signalosome) that contains the enzymes of the signaling pathway and
      that migrates to mitochondria to induce mitoKATP channel opening. We developed a
      novel method for isolating and purifying signalosomes from Langendorff-perfused
      rat hearts treated with bradykinin. Fractions containing the signalosomes were
      found to open mitoKATP channels in mitochondria isolated from untreated hearts
      via the activation of mitochondrial PKC-epsilon. mitoKATP channel opening
      required signalosome-dependent phosphorylation of an outer membrane protein.
      Immunodetection analysis revealed the presence of the bradykinin B2 receptor only
      in the fraction isolated from bradykinin-treated hearts. Immunodetection and
      immunogold labeling of caveolin-3, as well as sensitivity to cholesterol
      depletion and resistance to Triton X-100, attested to the caveolar nature of the
      signalosomes. Ischemic preconditioning, ischemic postconditioning, and perfusion
      with ouabain also led to active signalosome fractions that opened mitoKATP
      channels in mitochondria from untreated hearts. These results provide initial
      support for a novel mechanism for signal transmission from a plasma membrane
      receptor to mitoKATP channels.

PMID- 18621855
TI  - The impact of endurance exercise training on left ventricular systolic mechanics.
AB  - Although exercise training-induced changes in left ventricular (LV) structure are
      well characterized, adaptive functional changes are incompletely understood.
      Detailed echocardiographic assessment of LV systolic function was performed on 20
      competitive rowers (10 males and 10 females) before and after endurance exercise
      training (EET; 90 days, 10.7 +/- 1.1 h/wk). Structural changes included LV
      dilation (end-diastolic volume = 128 +/- 25 vs. 144 +/- 28 ml, P < 0.001), right
      ventricular (RV) dilation (end-diastolic area = 2,850 +/- 550 vs. 3,260 +/- 530
      mm2, P < 0.001), and LV hypertrophy (mass = 227 +/- 51 vs. 256 +/- 56 g, P <
      0.001). Although LV ejection fraction was unchanged (62 +/- 3% vs. 60 +/- 3%, P =
      not significant), all direct measures of LV systolic function were altered. Peak
      systolic tissue velocities increased significantly (basal lateral S'Delta = 0.9
      +/- 0.6 cm/s, P = 0.004; and basal septal S'Delta = 0.8 +/- 0.4 cm/s, P = 0.008).
      Radial strain increased similarly in all segments, whereas longitudinal strain
      increased with a base-to-apex gradient. In contrast, circumferential strain (CS)
      increased in the LV free wall but decreased in regions adjacent to the RV.
      Reductions in septal CS correlated strongly with changes in RV structure (DeltaRV
      end-diastolic area vs. DeltaLV septal CS; r2 = 0.898, P < 0.001) and function
      (Deltapeak RV systolic velocity vs. DeltaLV septal CS, r2 = 0.697, P < 0.001).
      EET leads to significant changes in LV systolic function with regional
      heterogeneity that may be secondary to concomitant RV adaptation. These changes
      are not detected by conventional measurements such as ejection fraction.

PMID- 18621854
TI  - Cardiac cholinergic NO-cGMP signaling following acute myocardial infarction and
      nNOS gene transfer.
AB  - Myocardial infarction (MI) is associated with oxidative stress, which may cause
      cardiac autonomic impairment. We tested the hypothesis that acute MI disrupts
      cardiac cholinergic signaling by impairing nitric oxide (NO)-cGMP modulation of
      acetylcholine (ACh) release and whether the restoration of this pathway following
      cardiac neuronal NO synthase (nNOS) gene transfer had any bearing on the neural
      phenotype. Guinea pigs underwent four ligature coronary artery surgery (n = 50)
      under general anesthesia to induce MI or sham surgery (n = 32). In a separate
      group, at the time of MI surgery, adenovirus encoding nNOS (n = 29) or enhanced
      green fluorescent protein (eGFP; n = 30) was injected directly into the right
      atria, where the postganglionic cholinergic neurons reside. In vitro-evoked right
      atrial [3H]ACh release, right atrial NOS activity, and cGMP levels were measured
      at 3 days. Post-MI 24% of guinea pigs died compared with 9% in the sham-operated
      group. Evoked right atrial [3H]ACh release was significantly (P < 0.05) decreased
      in the MI group as was NOS activity and cGMP levels. Tetrahydrobiopterin levels
      were not significantly different between the sham and MI groups. Infarct sizes
      between gene-transferred groups were not significantly different. The nNOS
      transduced group had significantly increased right atrial [3H]ACh release, right
      atrial NOS activity, cGMP levels, and decreased cAMP levels. Fourteen percent of
      the nNOS transduced animals died compared with 31% mortality in the MI + eGFP
      group at 3 days. In conclusion, cardiac nNOS gene transfer partially restores the
      defective NO-cGMP cholinergic pathway post-MI, which was associated with a trend
      of improved survival at 3 days.

PMID- 18621856
TI  - iNOS in cardiac myocytes plays a critical role in death in a murine model of
      hypertrophy induced by calcineurin.
AB  - Transgenic overexpression of calcineurin (CN/Tg) in mouse cardiac myocytes
      results in hypertrophy followed by dilation, dysfunction, and sudden death.
      Nitric oxide (NO) produced via inducible NO synthase (iNOS) has been implicated
      in cardiac injury. Since calcineurin regulates iNOS expression, and since
      phenotypes of mice overexpressing iNOS are similar to CN/Tg, we hypothesized that
      iNOS is pathogenically involved in cardiac phenotypes of CN/Tg mice. CN/Tg mice
      had increased serum and cardiac iNOS levels. When CN/Tg-iNOS(-/-) and CN/Tg mice
      were compared, some phenotypes were similar: extent of hypertrophy and fibrosis.
      However, CN/Tg-iNOS(-/-) mice had improved systolic performance (P < 0.001) and
      less heart block (P < 0.0001); larger sodium current density and lower serum TNF
      alpha levels (P < 0.03); and less apoptosis (P < 0.01) resulting in improved
      survival (P < 0.0003). To define tissue origins of iNOS production, chimeric
      lines were generated. Bone marrow (BM) from wild-type or iNOS(-/-) mice was
      transplanted into CN/Tg mice. iNOS deficiency restricted to BM-derived cells was
      not protective. Calcineurin activates the local production of NO by iNOS in
      cardiac myocytes, which significantly contributes to sudden death, heart block,
      left ventricular dilation, and impaired systolic performance in this murine model
      of cardiac hypertrophy induced by the overexpression of calcineurin.

PMID- 18621857
TI  - Sex and limb-specific ischemic reperfusion and vascular reactivity.
AB  - With little known regarding sex and limb heterogeneity, we investigated vascular
      reactivity and ischemic reperfusion (IR) in the upper and lower extremities of 15
      healthy men (26 +/- 2 yr) and women (23 +/- 1 yr). Doppler ultrasound was used to
      evaluate IR and flow-mediated dilation (FMD) after suprasystolic cuff occlusion
      in both the arm [brachial artery (BA)] and the leg [popliteal artery (PA)].
      Cumulative IR [area under the curve (AUC)], normalized for muscle mass, revealed
      no sex-related differences in either limb (forearm: men 38 +/- 3 and women 44 +/-
      4 ml/100 g; lower leg: men 12 +/- 2 and women 14 +/- 2 ml/100 g), while both
      groups revealed a greater IR per unit of arm muscle mass (AUC) compared with the
      lower leg (P < 0.05). The BA and PA were smaller in women (BA 0.31 +/- 0.1, PA
      0.47 +/- 0.1 cm) than in men (BA 0.41 +/- 0.1, PA 0.6 +/- 0.2 cm). Absolute
      FMD/shear rate revealed attenuated vascular function in the PA of the women
      [women 3.3 +/- 0.6, men 5.0 +/- 0.8 (all x10(-6)) cm/s(-1).s] and no sex
      difference in the BA [women 1.2 +/- 0.2, men 1.6 +/- 0.1 (all x10(-6)) cm/s(
      1).s]. In both sexes the PA demonstrated greater vascular reactivity than the BA.
      Thus vascular reactivity in healthy young people is greater in the legs,
      regardless of sex, and women have vascular function similar to men in the upper
      extremities but appear to have poorer vascular function normalized for shear rate
      in the lower extremities.

PMID- 18621858
TI  - Material properties of the ovine mitral valve anterior leaflet in vivo from
      inverse finite element analysis.
AB  - We measured leaflet displacements and used inverse finite-element analysis to
      define, for the first time, the material properties of mitral valve (MV) leaflets
      in vivo. Sixteen miniature radiopaque markers were sewn to the MV annulus, 16 to
      the anterior MV leaflet, and 1 on each papillary muscle tip in 17 sheep. Four
      dimensional coordinates were obtained from biplane videofluoroscopic marker
      images (60 frames/s) during three complete cardiac cycles. A finite-element model
      of the anterior MV leaflet was developed using marker coordinates at the end of
      isovolumic relaxation (IVR; when the pressure difference across the valve is
      approximately 0), as the minimum stress reference state. Leaflet displacements
      were simulated during IVR using measured left ventricular and atrial pressures.
      The leaflet shear modulus (G(circ-rad)) and elastic moduli in both the commisure
      commisure (E(circ)) and radial (E(rad)) directions were obtained using the method
      of feasible directions to minimize the difference between simulated and measured
      displacements. Group mean (+/-SD) values (17 animals, 3 heartbeats each, i.e., 51
      cardiac cycles) were as follows: G(circ-rad) = 121 +/- 22 N/mm2, E(circ) = 43 +/-
      18 N/mm2, and E(rad) = 11 +/- 3 N/mm2 (E(circ) > E(rad), P < 0.01). These values,
      much greater than those previously reported from in vitro studies, may result
      from activated neurally controlled contractile tissue within the leaflet that is
      inactive in excised tissues. This could have important implications, not only to
      our understanding of mitral valve physiology in the beating heart but for
      providing additional information to aid the development of more durable tissue
      engineered bioprosthetic valves.

PMID- 18621859
TI  - Characterization of blood borne microparticles as markers of premature coronary
      calcification in newly menopausal women.
AB  - While the risk for symptomatic atherosclerotic disease increases after menopause,
      currently recognized risk factors do not identify ongoing disease processes in
      low-risk women. This study tested the hypothesis that circulating cell-derived
      microparticles may reflect disease processes in women defined as low risk by the
      Framingham risk score. The concentration and phenotype of circulating
      microparticles were evaluated in a cross-sectional study of apparently healthy
      menopausal women, screened for enrollment into the Kronos Early Estrogen
      Prevention Study. Microparticles were evaluated by flow cytometry, and coronary
      artery calcification (CAC) was scored using 64-slice computed tomography
      scanners. The procoagulant activity of isolated microparticles was determined
      with a sensitive fluorescent thrombin generation assay. Chronological age, body
      mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%,
      range 1-3%), and high-sensitivity C-reactive protein did not differ significantly
      among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range,
      93-315 Agatston units) CAC compared with women without calcification. The total
      concentration and percentage of microparticles derived from platelets and
      endothelial cells were greatest in women with high CAC scores. The thrombin
      generating capacity of the isolated microparticles correlated with
      phosphatidylserine expression, which also was greatest in women with high CAC
      scores. The percentages of microparticles expressing granulocyte and monocyte
      markers were not significantly different among groups. Therefore, the
      characterization of platelet and endothelial microparticles may identify early
      menopausal women with premature CAC who would not otherwise be identified by the
      usual risk factor analysis.

PMID- 18621860
TI  - C-reactive protein and vein graft disease: evidence for a direct effect on smooth
      muscle cell phenotype via modulation of PDGF receptor-beta.
AB  - Plasma C-reactive protein (CRP) concentration is a biomarker of systemic
      atherosclerosis and may also be associated with vein graft disease. It remains
      unclear whether CRP is also an important modulator of biological events in the
      vessel wall. We hypothesized that CRP influences vein graft healing by
      stimulating smooth muscle cells (SMCs) to undergo a phenotypic switch.
      Distribution of CRP was examined by immunohistochemistry in prebypass human
      saphenous veins (HSVs, n = 21) and failing vein grafts (n = 18, 25-4,400 days
      postoperatively). Quiescent HSV SMCs were stimulated with human CRP (5-50
      microg/ml). SMC migration was assessed in modified Boyden chambers with platelet
      derived growth factor (PDGF)-BB (5-10 ng/ml) as the chemoattractant. SMC
      viability and proliferation were assessed by trypan blue exclusion and reduction
      of Alamar Blue substrate, respectively. Expression of PDGF ligand and receptor
      (PDGFR) genes was examined at RNA and protein levels after 24-72 h of CRP
      exposure. CRP staining was present in 13 of 18 diseased vein grafts, where it
      localized to the deep media and adventitia, but it was minimally detectable in
      most prebypass veins. SMCs pretreated with CRP demonstrated a dose-dependent
      increase in migration to PDGF-BB (P = 0.02), which was inhibited by a PDGF
      neutralizing antibody. SMCs treated with CRP showed a dose-dependent increase in
      PDGFRbeta expression and phosphorylation after 24-48 h. Exogenous CRP had no
      effect on SMC viability or proliferation. These data suggest that CRP is
      detectable within the wall of most diseased vein grafts, where it may exert local
      effects. Clinically relevant levels of CRP can stimulate SMC migration by a
      mechanism that may involve upregulation and activation of PDGFRbeta.

PMID- 18621861
TI  - Cardiovascular effects of prorenin blockade in genetically spontaneously
      hypertensive rats on normal and high-salt diet.
AB  - Recent reports have demonstrated a potential role of tissue prorenin in the
      pathogenesis of cardiovascular and renal damage. This study was designed to
      examine the role of prorenin in the pathogenesis of target organ damage in
      spontaneously hypertensive rats (SHRs), the best naturally occurring experimental
      model of essential hypertension. To this end, we studied 20-wk-old male SHRs
      receiving a normal diet and 8-wk-old male SHRs given food with 8% NaCl. One-half
      the rats in each group were given prorenin inhibitor (PRAM-1, 0.1 mg.kg(-1).day(
      1)) via osmotic minipumps; the other half served as controls. Arterial pressure,
      left ventricular function, cardiovascular mass indexes, cardiac fibrosis, and
      renal function were examined at the end of the experiment. Arterial pressure was
      unaffected by PRAM-1 in rats on either regular or salt-excess diets. In those
      rats receiving a normal diet, the blockade of prorenin activation consistently
      reduced left ventricular mass but affected no other variable. Salt-loaded rats
      given PRAM-1 for 8 wk demonstrated (1) reduced serum creatinine level, (2)
      decreased left ventricular mass, (3) improved left ventricular function, and (4)
      reduced left ventricular fibrosis. These data demonstrated that the blockade of
      nonproteolytic activation of prorenin exerted significant cardiovascular and
      renal benefit in SHRs with cardiovascular damage produced by salt excess and
      suggested that the activation of cardiovascular or renal prorenin may be a major
      mechanism that mediates cardiac and renal damage in this form of accelerated
      hypertension.

PMID- 18621862
TI  - Effect of heavy exercise on spectral baroreflex sensitivity, heart rate, and
      blood pressure variability in well-trained humans.
AB  - The aim of the study was to assess the instantaneous spectral components of heart
      rate variability (HRV) and systolic blood pressure variability (SBPV) and
      determine the low-frequency (LF) and high-frequency baroreflex sensitivity (HF
      BRS) during a graded maximal exercise test. The first hypothesis was that the
      hyperpnea elicited by heavy exercise could entail a significant increase in HF
      SBPV by mechanical effect once the first and second ventilatory thresholds (VTs)
      were exceeded. It was secondly hypothesized that vagal tone progressively
      withdrawing with increasing load, HF-BRS could decrease during the exercise test.
      Fifteen well-trained subjects participated in this study. Electrocardiogram
      (ECG), blood pressure, and gas exchanges were recorded during a cycloergometer
      test. Ventilatory equivalents were computed from gas exchange parameters to
      assess VTs. Spectral analysis was applied on cardiovascular series to compute RR
      and systolic blood pressure power spectral densities, cross-spectral coherence,
      gain, and alpha index of BRS. Three exercise intensity stages were compared:
      below (A1), between (A2), and above (A3) VTs. From A1 to A3, both HF-SBPV (A1: 45
      +/- 6, A2: 65 +/- 10, and A3: 120 +/- 23 mm2Hg, P < 0.001) and HF-HRV increased
      (A1: 20 +/- 5, A2: 23 +/- 8, and A3:40 +/- 11 ms2, P < 0.02), maintaining HF-BRS
      (gain, A1: 0.68 +/- 0.12, A2: 0.63 +/- 0.08, and A3: 0.57 +/- 0.09; alpha index,
      A1: 0.58 +/- 0.08, A2: 0.48 +/- 0.06, and A3: 0.50 +/- 0.09 ms/mmHg, not
      significant). However, LF-BRS decreased (gain, A1: 0.39 +/- 0.06, A2: 0.17 +/-
      0.02, and A3: 0.11 +/- 0.01, P < 0.001; alpha index, A1: 0.46 +/- 0.07, A2: 0.20
      +/- 0.02, and A3: 0.14 +/- 0.01 ms/mmHg, P < 0.001). As expected, once VTs were
      exceeded, hyperpnea induced a marked increase in both HF-HRV and HF-SBPV.
      However, this concomitant increase allowed the maintenance of HF-BRS, presumably
      by a mechanoelectric feedback mechanism.

PMID- 18621863
TI  - Feasibility of assessing the community composition of prasinophytes at the
      Helgoland Roads sampling site with a DNA microarray.
AB  - The microalgal class Prasinophyceae (Chlorophyta) contains several picoeukaryotic
      species, which are known to be common in temperate and cold waters and have been
      observed to constitute major fractions of marine picoplankton. However, reliable
      detection and classification of prasinophytes are mainly hampered by their small
      size and few morphological markers. Consequently, very little is known about the
      abundance and ecology of the members of this class. In order to facilitate the
      assessment of the abundance of the Prasinophyceae, we have designed and evaluated
      an 18S rRNA gene-targeted oligonucleotide microarray consisting of 21 probes
      targeting different taxonomic levels of prasinophytes. The microarray contains
      both previously published probes from other hybridization methods and new probes,
      which were designed for novel prasinophyte groups. The evaluation of the probe
      set was done under stringent conditions with 18S PCR fragments from 20 unialgal
      reference cultures used as positive targets. This microarray has been applied to
      assess the community composition of prasinophytes at Helgoland, an island in the
      North Sea where time series data are collected and analyzed daily but only for
      the nano- and microplankton-size fractions. There is no identification of
      prasinophytes other than to record them numerically in the flagellate fraction.
      The samples were collected every 2 weeks between February 2004 and December 2006.
      The study here demonstrates the potential of DNA microarrays to be applied as a
      tool for quick general monitoring of this important picoplanktonic algal group.

PMID- 18621864
TI  - Short-term response of soil bacteria to carbon enrichment in different soil
      microsites.
AB  - The response of bacteria in bulk soil and earthworm casts to carbon enrichment
      was studied by an RNA stable-isotope probing/terminal restriction fragment length
      polymorphism strategy with (13)C-labeled glucose and acetate. Both the soil
      microsite status and the carbon enrichment selected rapidly for different active
      bacterial communities, which resulted in different degradation kinetics. Our
      study clearly illustrates the biases that are generated by adding C substrates to
      detect metabolically active bacteria in soil.

PMID- 18621865
TI  - Real-time PCR detection of pathogenic microorganisms in roof-harvested rainwater
      in Southeast Queensland, Australia.
AB  - In this study, the microbiological quality of roof-harvested rainwater was
      assessed by monitoring the concentrations of Escherichia coli, enterococci,
      Clostridium perfringens, and Bacteroides spp. in rainwater obtained from tanks in
      Southeast Queensland, Australia. Samples were also tested using real-time PCR
      (with SYBR Green I dye) for the presence of potential pathogenic microorganisms.
      Of the 27 rainwater samples tested, 17 (63%), 21 (78%), 13 (48%), and 24 (89%)
      were positive for E. coli, enterococci, C. perfringens, and Bacteroides spp.,
      respectively. Of the 27 samples, 11 (41%), 7 (26%), 4 (15%), 3 (11%), and 1 (4%)
      were PCR positive for the Campylobacter coli ceuE gene, the Legionella
      pneumophila mip gene, the Aeromonas hydrophila lip gene, the Salmonella invA
      gene, and the Campylobacter jejuni mapA gene. Of the 21 samples tested, 4 (19%)
      were positive for the Giardia lamblia beta-giardin gene. The binary logistic
      regression model indicated a positive correlation (P < 0.02) between the
      presence/absence of enterococci and A. hydrophila. In contrast, the
      presence/absence of the remaining potential pathogens did not correlate with
      traditional fecal indicators. The poor correlation between fecal indicators and
      potential pathogens suggested that fecal indicators may not be adequate to assess
      the microbiological quality of rainwater and consequent health risk.

PMID- 18621866
TI  - Distinct contributions of the nisin biosynthesis enzymes NisB and NisC and
      transporter NisT to prenisin production by Lactococcus lactis.
AB  - Several Lactococcus lactis strains produce the lantibiotic nisin. The dedicated
      enzymes NisB and NisC and the transporter NisT modify and secrete the ribosomally
      synthesized nisin precursor peptide. NisB can function in the absence of the
      cyclase NisC, yielding the dehydrated prenisin that lacks the thioether rings. A
      kinetic analysis of nisin production by L. lactis NZ9700 demonstrated that the
      prenisin was released from the cell into the medium before the processing of the
      leader sequence occurred. Upon the deletion of nisC, the production of prenisin
      was reduced by 70%, while in the absence of nisB, the production of prenisin was
      nearly completely abolished. In cells lacking nisT, no secretion was observed,
      while the expression of nisABC in these cells resulted in considerable growth
      rate inhibition caused by the intracellular accumulation of active nisin.
      Overall, these data indicate that the efficiency of prenisin transport by NisT is
      markedly enhanced by NisB, suggesting a channeling mechanism of prenisin transfer
      between the nisin modification enzymes and the transporter.

PMID- 18621867
TI  - Baseline data from a Belgium-wide survey of Campylobacter species contamination
      in chicken meat preparations and considerations for a reliable monitoring
      program.
AB  - From February to November 2007, chicken meat preparations (n = 656) were sampled
      at 11 processing companies across Belgium. All samples were tested for
      Campylobacter by enrichment culture and by direct plating according to standard
      methods. Almost half (48.02%) of the samples were positive for Campylobacter spp.
      The mean Campylobacter count was 1.68 log(10) CFU/g with a standard deviation of
      +/- 0.64 log(10) CFU/g. The study revealed a statistically significant variation
      in Campylobacter contamination levels between companies; processors with a wider
      frequency distribution range of Campylobacter counts provided chicken meat
      preparations with higher Campylobacter incidences and concentrations. There was
      no significant difference between the counts of Campylobacter spp. in various
      preparation types. However, the Campylobacter counts and incidences in chicken
      wings were the highest and portioned-form products (legs, wings, and breasts)
      showed a higher probability of being Campylobacter positive compared to minced
      form products (sausages, burgers, and minced meat). The proportion of
      Campylobacter-positive samples was significantly higher in July than in other
      months. Recovery of Campylobacter spp. recovery by direct plating was higher
      (41.0%) compared to detection after enrichment (24.2%). Statistical modeling of
      the survey data showed that the likelihood of obtaining a positive result by
      enrichment culture increases with an increase in the Campylobacter concentration
      in the sample. In the present study, we provide the first enumeration data on
      Campylobacter contamination in Belgian chicken meat preparations and address
      proposals for improving Campylobacter monitoring programs.

PMID- 18621868
TI  - Bacteriophage P22 and Staphylococcus aureus attenuation on nonporous fomites as
      determined by plate assay and quantitative PCR.
AB  - Decay rates of bacteriophage P22 and Staphylococcus aureus on six types of common
      household inanimate surfaces were evaluated based on cultivation and quantitative
      PCR. A much higher level of inactivation was observed using the plate assay,
      suggesting that detection of the pathogen genome in samples from fomites does not
      necessarily imply a health risk to humans.

PMID- 18621869
TI  - Importance of type II secretion for survival of Legionella pneumophila in tap
      water and in amoebae at low temperatures.
AB  - Legionella pneumophila type II secretion mutants showed reduced survival in both
      tap water at 4 to 17 degrees C and aquatic amoebae at 22 to 25 degrees C. Wild
      type supernatants stimulated the growth of these mutants, indicating that
      secreted factors promote low-temperature survival. There was a correlation
      between low-temperature survival and secretion function when 12 additional
      Legionella species were examined.

PMID- 18621870
TI  - Corynebacterium glutamicum contains 3-deoxy-D-arabino-heptulosonate 7-phosphate
      synthases that display novel biochemical features.
AB  - 3-Deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase (EC 2.5.1.54)
      catalyzes the first step of the shikimate pathway that finally leads to the
      biosynthesis of aromatic amino acids phenylalanine (Phe), tryptophan (Trp), and
      tyrosine (Tyr). In Corynebacterium glutamicum ATCC 13032, two chromosomal genes,
      NCgl0950 (aroF) and NCgl2098 (aroG), were located that encode two putative DAHP
      synthases. The deletion of NCgl2098 resulted in the loss of the ability of C.
      glutamicum RES167 (a restriction-deficient strain derived from C. glutamicum ATCC
      13032) to grow in mineral medium; however, the deletion of NCgl0950 did not
      result in any observable phenotypic alteration. Analysis of DAHP synthase
      activities in the wild type and mutants of C. glutamicum RES167 indicated that
      NCgl2098, rather than NCgl0950, was involved in the biosynthesis of aromatic
      amino acids. Cloning and expression in Escherichia coli showed that both NCgl0950
      and NCgl2098 encoded active DAHP synthases. Both the NCgl0950 and NCgl2098 DAHP
      synthases were purified from recombinant E. coli cells and characterized. The
      NCgl0950 DAHP synthase was sensitive to feedback inhibition by Tyr and, to a much
      lesser extent, by Phe and Trp. The NCgl2098 DAHP synthase was slightly sensitive
      to feedback inhibition by Trp, but not sensitive to Tyr and Phe, findings that
      were in contrast to the properties of previously known DAHP synthases from C.
      glutamicum subsp. flavum. Both Co2+ and Mn2+ significantly stimulated the
      NCgl0950 DAHP synthase's activity, whereas Mn2+ was much more stimulatory than
      Co2+ to the NCgl2098 DAHP synthase's activity.

PMID- 18621871
TI  - Isolation of predation-deficient mutants of Bdellovibrio bacteriovorus by using
      transposon mutagenesis.
AB  - The availability of the complete genome sequence of Bdellovibrio bacteriovorus
      provides an opportunity for investigating genes that play a significant role in
      predation. Using two independently derived facultatively predatory Bdellovibrio
      strains, we have designed a method to cultivate and screen transposon insertion
      mutants in 96-well microtiter dishes. Transposon insertion mutants were produced
      by introducing the plasposon pRL27, which carries a mini-Tn5. Mutants have been
      screened for predatory activity using 96-well plates. Seventeen independent
      nonpredatory mutants have been isolated, and DNA flanking the insertion has been
      sequenced. BLAST analysis revealed that most of these interrupted DNA sequences
      do not code for known proteins or functions. Two of the inactivated genes were
      analyzed further: one was found to code for a putative serine protease and the
      other a probable protein involved in secretion through the outer membrane. The
      methods described here are the first for the generation and isolation of
      predation-deficient mutants using random-transposon-insertion mutagenesis. As
      more mutants are isolated and their gene products analyzed, more light will be
      shed on how this predator carries out its exclusive life processes and perhaps
      how these products, or the organism itself, can be used for therapeutic,
      agricultural, and/or other purposes.

PMID- 18621872
TI  - Cryptosporidium genotypes and subtypes in lambs and goat kids in Spain.
AB  - To provide information on the transmission dynamics of cryptosporidial infections
      in domestic small ruminants and the potential role of sheep and goats as a source
      for human cryptosporidiosis, Cryptosporidium-positive isolates from 137 diarrheic
      lambs and 17 goat kids younger than 21 days of age were examined by using
      genotyping and subtyping techniques. Fecal specimens were collected between 2004
      and 2006 from 71 sheep and 7 goat farms distributed throughout Aragon
      (northeastern Spain). Cryptosporidium parvum was the only species identified by
      restriction analyses of PCR products from small-subunit rRNA genes from all 154
      microscopy-positive isolates and the sequencing of a subset of 50 isolates.
      Sequence analyses of the glycoprotein (GP60) gene revealed extensive genetic
      diversity within the C. parvum strains in a limited geographical area, in which
      the isolates from lambs exhibited 11 subtypes in two subtype families (IId and
      IIa) and those from goat kids displayed four subtypes within the family IId. Most
      isolates (98%) belonged to the subtype family IId, whereas only three isolates
      belonged to the most widely distributed family, IIa. Three of the four most
      prevalent subtypes (IIdA17G1a, IIdA19G1, and IIdA18G1) were previously identified
      in humans, and five subtypes (IIdA14G1, IIdA15G1, IIdA24G1, IIdA25G1, and
      IIdA26G1) were novel subtypes. All IId subtypes were identical to each other in
      the nonrepeat region, except for subtypes IIdA17G1b and IIdA22G1, which differed
      by a single nucleotide polymorphism downstream of the trinucleotide repeats.
      These findings suggest that lambs and goat kids are an important reservoir of the
      zoonotic C. parvum subtype family IId for humans.

PMID- 18621874
TI  - Methylotrophy in freshwater Beggiatoa alba strains.
AB  - Two freshwater strains of the gammaproteobacterium Beggiatoa alba, B18LD and OH75
      2a, are able to use methanol as a sole carbon and energy source under microoxic
      conditions. Genes encoding a methanol dehydrogenase large-subunit homolog and
      four enzymes of the tetrahydromethanopterin-dependent C(1) oxidation pathway were
      identified in B18LD. No evidence of methanotrophy was detected.

PMID- 18621875
TI  - Molecular characterization of the bacterial communities in the different
      compartments of a full-scale reverse-osmosis water purification plant.
AB  - The origin, structure, and composition of biofilms in various compartments of an
      industrial full-scale reverse-osmosis (RO) membrane water purification plant were
      analyzed by molecular biological methods. Samples were taken when the RO
      installation suffered from a substantial pressure drop and decreased production.
      The bacterial community of the RO membrane biofilm was clearly different from the
      bacterial community present at other locations in the RO plant, indicating the
      development of a specialized bacterial community on the RO membranes. The typical
      freshwater phylotypes in the RO membrane biofilm (i.e., Proteobacteria, Cytophaga
      Flexibacter-Bacteroides group, and Firmicutes) were also present in the water
      sample fed to the plant, suggesting a feed water origin. However, the relative
      abundances of the different species in the mature biofilm were different from
      those in the feed water, indicating that the biofilm was actively formed on the
      RO membrane sheets and was not the result of a concentration of bacteria present
      in the feed water. The majority of the microorganisms (59% of the total number of
      clones) in the biofilm were related to the class Proteobacteria, with a dominance
      of Sphingomonas spp. (27% of all clones). Members of the genus Sphingomonas seem
      to be responsible for the biofouling of the membranes in the RO installation.

PMID- 18621877
TI  - Somatechnics of medico-legal taxonomies: elective amputation and transableism.

PMID- 18621876
TI  - The lamin B receptor under transcriptional control of C/EBPepsilon is required
      for morphological but not functional maturation of neutrophils.
AB  - The lamin B receptor (LBR) is an integral nuclear envelope protein that interacts
      with chromatin and has homology to sterol reductases. Mutations in LBR result in
      Pelger-Huet anomaly and HEM-Greenberg skeletal dysplasia, whereas in mice Lbr
      mutations result in ichthyosis. To further understand the function of the LBR and
      its role in disease, we derived a novel mouse model with a gene-trap insertion
      into the Lbr locus (Lbr(GT/GT)). Phenotypically, the Lbr(GT/GT) mice are similar
      to ichthyosis mice. The Lbr(GT/GT) granulocytes lack a mature segmented nucleus
      and have a block in late maturation. Despite these changes in nuclear morphology,
      the innate granulocyte immune function in the killing of Staphylococcus aureus
      bacteria appears to be intact. Granulocyte differentiation requires the
      transcription factor C/EBPepsilon. We identified C/EBPepsilon binding sites
      within the Lbr promoter and used EMSAs and luciferase assays to show that Lbr is
      transcriptionally regulated by C/EBPepsilon. Our findings indicate that the
      Lbr(GT/GT) mice are a model for Pelger-Huet anomaly and that Lbr, under
      transcriptional regulation of C/EBPepsilon, is necessary for morphological but
      not necessarily functional granulocyte maturation.

PMID- 18621878
TI  - The use of arterial closure devices for incidental arterial injury.
AB  - Incidental arterial injury is one of the main mechanical complications associated
      with central venous catheter placement. These injuries can result in significant
      morbidity and mortality. The use of arterial closure devices to repair these
      injuries offers a less invasive alternative than open repair and a safer approach
      than manual compression. We present 3 cases of critically ill patients treated
      with arterial closure devices when attempted central venous catheterization
      failed and inadvertent arterial cannulation occurred. A brief review of the
      various closure devices and there indications is discussed.

PMID- 18621879
TI  - Effect of preoperative renal dysfunction on mortality and postoperative renal
      failure following endovascular abdominal aortic aneurysm repair.
AB  - This study was aimed to assess the effect of preoperative renal dysfunction on
      mortality and postoperative renal failure in patients undergoing elective
      endovascular repair of abdominal aortic aneurysm. A total of 155 patients with a
      mean age of 74.9 years (+/-6.4) were included. In all, 31 patients (20%) had a
      preoperative creatinine level of >1.5 mg/dL, whereas 66 patients (42.6%) had an
      estimated glomerular filtration rate of <60 mL/min. Perioperative mortality was
      2.6% with no significant difference between those with and without abnormal renal
      indices. Long-term survival at 4 years was 30% in patients with creatinine >1.5
      mg/dL compared to over 60% in those with normal creatinine (P < .02). The
      difference in long-term survival was not as significant in patients with normal
      or reduced glomerular filtration rate (P = .13). However, neither creatinine nor
      glomerular filtration rate were found to accurately predict survival even though
      both demonstrated strong predictivity for postoperative renal failure in patients
      undergoing elective endovascular repair of abdominal aortic aneurysm.

PMID- 18621873
TI  - Selective isolation and rapid identification of members of the genus
      Micromonospora.
AB  - Improved methods for selective isolation of diverse actinomycetes of the genus
      Micromonospora and a genus-specific nested PCR for rapid identification of
      putative Micromonospora isolates were developed. The robustness of both the
      isolation and the identification approach was underpinned by phylogenetic
      analysis based on 16S rRNA gene sequences.

PMID- 18621880
TI  - Nicotinamide adenine dinucleotide phosphate oxidase and diabetes: vascular
      implications.
AB  - Vascular disease associated with diabetes mellitus is a major cause of morbidity
      and mortality and is increasing in the United States. It is now recognized that
      oxidative stress plays a substantial role in the underlying vascular pathology of
      several diseases, including hypertension and diabetes. In diabetes, there is an
      increase in the steady state levels of reactive oxygen species. One of the
      primary generators of reactive oxygen species is nicotinamide adenine
      dinucleotide phosphate oxidase. Studies have indicated that inhibition of this
      system is associated with vascular benefits in diabetes. Therefore, there may be
      a role for therapies directed at nicotinamide adenine dinucleotide phosphate
      oxidase in this disease. This review will examine the structure, activation,
      potential role in vascular disease, and benefits of inhibition of nicotinamide
      adenine dinucleotide phosphate oxidase.

PMID- 18621881
TI  - Evolving strategies in treatment of isolated symptomatic innominate artery
      disease.
AB  - PURPOSE: To examine the evolving roles of endovascular and open approaches in
      treatment of symptomatic innominate artery (IA) disease. METHODS: Patients
      treated for symptomatic IA lesions with or without involvement of the right
      common carotid and/or right subclavian arteries between 1997 and 2006 were
      identified. Charts and diagnostic studies were retrospectively reviewed. RESULTS:
      Of 18 patients treated, 8 required open reconstruction. Ten patients with high
      grade focal stenosis were stented. Immediate technical and clinical success was
      100% among all patients. Mean follow-up time was 25 and 27 months for
      endovascular and open interventions, respectively. The primary patency rates were
      78% +/- 14 and 80% +/- 10 for endovascular and open groups, respectively.
      Assisted primary patency rate was 100% for both groups. There were no peri
      operative mortalities or neurological events. We encountered two systemic
      (pulmonary) complications and one access-related complication among open and
      endovascular patients, respectively. CONCLUSION: Endovascular repair is evolving
      as a primary mode of therapy for focal IA lesions while open approach is reserved
      for more extensive disease. Patho-anatomical characteristics of a given IA lesion
      along with peri-operative risk assessment determine a proper surgical approach.

PMID- 18621882
TI  - Modified trapdoor exposure for open repair of brachiocephalic artery branch
      injury: case report.
AB  - Central venous catheterization is associated with a wide spectrum of vascular
      complications, including inadvertent arterial puncture. We describe 2 cases of
      successful open surgical repair of iatrogenic cervicothoracic arterial injuries
      secondary to central venous catheterization. In both patients, a novel
      transmanubrial approach was incorporated to expose and control the
      brachiocephalic artery.

PMID- 18621883
TI  - Single-center experience of caval thrombectomy in patients with renal cell
      carcinoma with tumor thrombus extension into the inferior vena cava.
AB  - The objective of this study is to describe a single-center experience of caval
      thrombectomy in patients with renal cell carcinoma (RCC) and tumor thrombus
      extension into the inferior vena cava (IVC). We retrospectively reviewed 23
      patients undergoing radical nephrectomy with caval thrombectomy. Follow-up
      included an office visit and computed tomography scan. Statistical comparisons
      were made using 2-sample t tests. Patients' ages ranged from 32 to 83 years
      (mean, 62 years; 18 male, 5 female). Tumor size ranged from 3 to 21 cm (mean, 8.6
      cm). Tumor thrombus staging was based on the Nevus classification: level I
      (2/23), II (6/23), III (13/26), IV (2/23). Tumor thrombi were removed by means of
      digital extraction (20), Fogarty embolectomy (2), or endarterectomy (1-caval wall
      invasion). Lateral venorrhaphy was used for IVC repair in all cases. Hepatic
      mobilization and suprahepatic clamping were necessary in 14 patients. Clamp times
      were significantly different between the suprahepatic (SH) and infrahepatic (IH)
      groups (15 vs 9.4 minutes, P < .012). Mean blood loss was also significantly
      different (3.2 L vs 2 L, P < .045). In the SH group, 2 patients developed
      postoperative atrial fibrillation and 2 patients died (respiratory failure;
      missed enterotomy). The IH group had no perioperative morbidity or mortality.
      Median followup was 15 months (range, 1-54 months). Follow-up imaging was
      available for 19/23 patients. Ninety-five percent of patients had a patent IVC
      (18). One SH patient developed an IVC stenosis/thrombosis 12 months
      postoperatively with successful thrombolysis and stenting. There was a 16% (3/19)
      recurrence rate in follow-up, with all patients demonstrating renal vascular
      invasion and high Fuhrman grade upon final pathologic evaluation. Caval
      thrombectomy can be performed safely during radical nephrectomy for RCC with
      tumor thrombus extension. The need for suprahepatic clamping is associated with
      longer clamp times, increased blood loss, and increased morbidity and mortality.
      Lateral venorrhaphy with primary repair avoids complicated caval reconstructions
      and results in high patency rates, despite a not insignificant recurrence rate.

PMID- 18621884
TI  - Associations between statin treatment and markers of inflammation,
      vasoconstriction, and coagulation in patients with abdominal aortic aneurysm.
AB  - The association of statins with markers of inflammation, vasoconstriction, and
      coagulation was evaluated in 325 patients with abdominal aortic aneurysm with
      respect to statin treatment or not. Variables evaluated included routine
      laboratory markers, lipids, homocysteine, endothelin-1, matrix metalloproteinases
      (MMP)-2 and -9, and activated protein C-protein C inhibitor (APC-PCI) complex.
      Statin-treated patients were more often male (85% vs 75%; P = .024) and had
      ischemic heart disease (57% vs 19%; P < .0001). They showed lower levels of
      cholesterol (P < .0001), homocysteine (P = .027), MMP-9 (P = .038), and
      endothelin-1 (P = .005), and higher levels of APC-PCI complex (P = .042).
      Differences persisted in logistic regression for cholesterol (P < .0001), APC-PCI
      complex (P = .034), and homocysteine (P = .021). Statin-treated patients with
      abdominal aortic aneurysm show higher APC-PCI complex and lower homocysteine
      levels. Whether this translates into lower risk for aneurysm expansion or rupture
      will be evident from further follow-up.

PMID- 18621885
TI  - Aneurysm regression after endovascular aneurysm repair: what should we expect?
AB  - This study reviewed a large national core laboratory database for the Ancure
      (Guidant, Menlo Park, California) phase I and II trial of overall aneurysm sac
      regression after endovascular aneurysm repair. Data were reviewed for aneurysm
      size and endoleak in follow-up. Endoleak was recorded as well as maximum major
      and minor axis aortic diameters. Included were patients with baseline assessment
      within 3 months of implantation and at least 24 months of follow-up, and 444 were
      available for review. The mean baseline aortic diameter was 56.6 mm; mean follow
      up was 48.7 months. Of these patients, 129 (29.5%) had aneurysm regression to
      less than 40 mm, 42 (9.5%) regressed to less than 35 mm, and 12 (2.7%) had
      complete aneurysm sac obliteration. Multivariate analysis demonstrated that
      baseline aneurysm size was the only predictor of aneurysm size regression.
      Significant sac regression is common after Ancure aneurysm repair and appears to
      be related primarily to initial aneurysm size.

PMID- 18621887
TI  - The role of statin drugs in the management of the peripheral vascular patient.
AB  - The impact of statin therapy on established vascular conditions and recurrent
      disease is most relevant for long-term care. Patients receiving statin therapy
      have been shown to experience less recurrent stenosis following carotid
      endarterectomy and stent angioplasty, reduced cardiac events following cardiac
      and noncardiac vascular surgery, and reduction in aneurysm development. In
      patients with peripheral arterial disease, claudication distance is increased, as
      well as patency rates following infrainguinal arterial bypass grafting. Of note,
      statins drugs may also prove beneficial in the prevention of certain cancers,
      Alzheimer's disease, and osteoporosis (all diseases frequently seen concurrently
      in the patient with peripheral arterial disease). As such, it is becoming all the
      more necessary that vascular surgeons remain informed about clinical research
      initiatives related to statin use and lipid management in general. The following
      is a review of lipid metabolism as it applies to statins as well as a review of
      the beneficial effects of statins.

PMID- 18621886
TI  - Assessment of aortic pathology and peripheral arterial disease using
      multidetector computed tomographic angiography.
AB  - The development of multidetector computed tomography represents a remarkable
      diagnostic advancement because this imaging modality has been widely used in the
      evaluation of the cardiovascular system. With scanner-adjusted image acquisition
      and contrast medium administration, multidetector computed tomographic
      angiography provides a cost-effective and accurate imaging assessment in patients
      with aortic pathologies or peripheral arterial occlusive disease. Multidetector
      computed tomographic angiography is associated with several advantages, including
      high image spatial resolution and rapid imaging acquisition speed. This
      diagnostic methodology allows accurate detection of a variety of intravascular
      lesions in the carotid artery, thoracic and abdominal aorta, renal arteries, and
      peripheral arterial systems. This article provides an overview of multidetector
      computed tomographic angiography in the assessment of arterial disease and
      reviews current literature about this diagnostic technology in the evaluation of
      aortic and peripheral arterial pathologies.

PMID- 18621888
TI  - Endovascular repair of symptomatic renal transplant site pseudoaneurysm.
AB  - This article reports a patient with a symptomatic external iliac artery
      pseudoaneurysm at a prior transplant nephrectomy site who underwent successful
      repair with percutaneous endovascular placement of a covered stent. Endovascular
      treatment with a covered stent is a safe and effective alternative to open
      surgery in the treatment of a symptomatic pseudoaneurysm arising from a
      transplant nephrectomy site.

PMID- 18621889
TI  - Use of the abdominal aorta as an alternative access site for thoracic aortic
      stent graft placement.
AB  - The treatment of thoracic aortic pathology has undergone a paradigm shift in
      recent years, with a trend toward less invasive endovascular techniques and away
      from open surgical repair. Reports on the successful use of endografts in the
      thoracic aorta have demonstrated decreased morbidity and mortality of these
      procedures compared with traditional open repair. However, some patients are not
      candidates for an endovascular approach because of a short proximal landing zone,
      arch angulation, luminal irregularities, or a large diameter of the transverse
      arch and the proximal descending aorta. Other patients are excluded because of
      distal pathology or anatomic irregularities. This article presents 2 patients
      with thoracic aortic pathology, and both had inadequate proximal landing zones
      and small, calcified iliac arteries prohibiting femoral or iliac access.
      Successful repair of these patients was achieved by a staged procedure using a
      brachiocephalic debranching technique, followed by direct infrarenal aortic
      cannulation through a limited celiotomy.

PMID- 18621890
TI  - Successful repair of popliteal artery pseudoaneurysm after tibial lengthening
      osteotomy in a 7-year-old boy.
AB  - Popliteal artery injury is a known but rare complication of elective orthopedic
      procedures. This case report describes the diagnosis and treatment of a popliteal
      artery pseudoaneurysm and arteriovenous fistula after a tibial lengthening
      osteotomy in a 7-year-old boy.

PMID- 18621891
TI  - Analysis of a growth-phase-regulated two-component regulatory system in the
      periodontal pathogen Treponema denticola.
AB  - Nothing is currently known regarding the global regulatory networks of Treponema
      denticola and other oral spirochetes. In this report, we assess the properties
      and potential phosphotransfer capability of a putative two-component regulatory
      system (TCS) of T. denticola that is formed by the products of open reading
      frames tde0032 (a sensor kinase) and tde0033 (a response regulator), henceforth
      designated AtcS and AtcR, respectively. Using PCR and DNA sequence analyses, atcS
      and atcR were demonstrated to be widely distributed and conserved among T.
      denticola isolates. Reverse transcription-PCR (RT-PCR) analyses revealed that
      these genes are cotranscribed and may also be expressed as part of a larger
      operon that includes several flanking genes. Analyses using 5' rapid
      amplification of cDNA ends identified the transcriptional start sites for these
      operons and provided evidence that some of these genes may be independently
      transcribed from internal promoters. Real-time RT-PCR and Western blot analysis
      revealed significant upregulation of atcRS during late-stage growth, indicating
      growth-phase-dependent expression. Lastly, the phosphorelay capability of the
      AtcRS system was assessed and demonstrated using recombinant proteins. AtcS was
      found to undergo autophosphorylation and to transfer phosphate to AtcR. These
      analyses represent the first description of a functional TCS in an oral
      spirochetes and provide insight into the transcriptional regulatory mechanisms of
      these important bacteria.

PMID- 18621892
TI  - Biosynthesis of a rare di-N-acetylated sugar in the lipopolysaccharides of both
      Pseudomonas aeruginosa and Bordetella pertussis occurs via an identical scheme
      despite different gene clusters.
AB  - Pseudomonas aeruginosa and Bordetella pertussis produce lipopolysaccharide (LPS)
      that contains 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid (D-ManNAc3NAcA). A
      five-enzyme biosynthetic pathway that requires WbpA, WbpB, WbpE, WbpD, and WbpI
      has been proposed for the production of this sugar in P. aeruginosa, based on
      analysis of genes present in the B-band LPS biosynthesis cluster. In the
      analogous B. pertussis cluster, homologs of wbpB to wbpI were present, but a
      putative dehydrogenase gene was missing; therefore, the biosynthetic mechanism
      for UDP-D-ManNAc3NAcA was unclear. Nonpolar knockout mutants of each P.
      aeruginosa gene were constructed. Complementation analysis of the mutants
      demonstrated that B-band LPS production was restored to P. aeruginosa knockout
      mutants when the relevant B. pertussis genes were supplied in trans. Thus, the
      genes that encode the putative oxidase, transaminase, N-acetyltransferase, and
      epimerase enzymes in B. pertussis are functional homologs of those in P.
      aeruginosa. Two candidate dehydrogenase genes were located by searching the B.
      pertussis genome; these have 80% identity to P. aeruginosa wbpO (serotype O6) and
      32% identity to wbpA (serotype O5). These genes, wbpO(1629) and wbpO(3150), were
      shown to complement a wbpA knockout of P. aeruginosa. Capillary electrophoresis
      was used to characterize the enzymatic activities of purified WbpO(1629) and
      WbpO(3150), and mass spectrometry analysis confirmed that the two enzymes are
      dehydrogenases capable of converting UDP-D-GlcNAc, UDP-D-GalNAc, to a lesser
      extent, and UDP-D-Glc, to a much lesser extent. Together, these results suggest
      that B. pertussis produces UDP-D-ManNAc3NAcA through the same pathway proposed
      for P. aeruginosa, despite differences in the genomic context of the genes
      involved.

PMID- 18621893
TI  - Characterization of the accessory Sec system of Staphylococcus aureus.
AB  - The SraP adhesin of Staphylococcus aureus is a member of a highly conserved
      family of serine-rich surface glycoproteins of gram-positive bacteria. For
      streptococci, export of the SraP homologs requires a specialized transport
      pathway (the accessory Sec system). Compared to streptococci, however, SraP is
      predicted to differ in its signal peptide and glycosylation, which may affect its
      dependence on a specialized system for transport. In addition, two genes (asp4
      and asp5) essential for export in Streptococcus gordonii are missing in S.
      aureus. Thus, the selectivity of the accessory Sec system in S. aureus may also
      differ compared to streptococci. To address these issues, the five genes encoding
      the putative accessory Sec system (secY2, secA2, and asp1-3) were disrupted
      individually in S. aureus ISP479C, and the resultant mutants were examined for
      SraP export. Disruption of secA2 resulted in the near complete loss of SraP
      surface expression. Similar results were seen with disruption of secY2 and asp1,
      asp2, or asp3. To assess whether the accessory Sec system transported other
      substrates, we compared secreted proteomes of ISP479C and a secA2 isogenic
      mutant, by two-dimensional fluorescence difference gel electrophoresis. Although
      two consistent differences in proteome content were noted between the strains,
      neither protein appeared to be a likely substrate for accessory Sec export. Thus,
      the accessory Sec system of S. aureus is required for the export of SraP, and it
      appears to be dedicated to the transport of this substrate exclusively.

PMID- 18621894
TI  - Cell surface structures of archaea.

PMID- 18621895
TI  - Protein aggregates: an aging factor involved in cell death.
AB  - In a previous study, we demonstrated the presence of protein aggregates in an
      exponentially grown Escherichia coli culture. In light of these observations,
      protein aggregates could be considered damage to cells that is able to pass from
      one generation to the next. Based on the assumption that the amount of aggregate
      protein could represent an aging factor, we monitored this amount in a bacterial
      culture during senescence. In doing so, we observed (i) a significant increase in
      the amount of aggregate protein over time, (ii) a proportional relationship
      between the amount of aggregate protein and the level of dead cells, (iii) a
      larger amount in dead cells than in culturable cells, (iv) a heterogeneous
      distribution of different amounts within a homogenous population of culturable
      cells entering stasis, and (v) that the initial amount of aggregate protein
      within a culturable population conditioned the death rate of the culture.
      Together, the results presented in this study suggest that protein aggregates
      indeed represent one aging factor leading to bacterial cell death.

PMID- 18621896
TI  - Mutational analysis of the connector segment in the HAMP domain of Tsr, the
      Escherichia coli serine chemoreceptor.
AB  - HAMP domains are approximately 50-residue motifs, found in many bacterial
      signaling proteins, that consist of two amphiphilic helices joined by a
      nonhelical connector segment. The HAMP domain of Tsr, the serine chemoreceptor of
      Escherichia coli, receives transmembrane input signals from the periplasmic
      serine binding domain and in turn modulates output signals from the Tsr kinase
      control domain to elicit chemotactic responses. We created random amino acid
      replacements at each of the 14 connector residues of Tsr-HAMP to identify those
      that are critical for Tsr function. In all, we surveyed 179 connector missense
      mutants and identified three critical residues (G235, L237, and I241) at which
      most replacements destroyed Tsr function and another important residue (G245) at
      which most replacements impaired Tsr function. The region surrounding G245
      tolerated 1-residue deletions and insertions of up to 10 glycines, suggesting a
      role as a relatively nonspecific, flexible linker. The critical connector
      residues are consistent with a structural model of the Tsr-HAMP domain based on
      the solution structure of an isolated thermophile HAMP domain (M. Hulko, F.
      Berndt, M. Gruber, J. U. Linder, V. Truffault, A. Schultz, J. Martin, J. E.
      Schultz, A. N. Lupas, and M. Coles, Cell 126:929-940, 2006) in which G235 defines
      a critical turn at the C terminus of the first helix and L237 and I241 pack
      against the helices, perhaps to stabilize alternative HAMP signaling
      conformations. Most I241 lesions locked Tsr signal output in the kinase-on mode,
      implying that this residue is responsible mainly for stabilizing the kinase-off
      signaling state. In contrast, lesions at L237 resulted in a variety of aberrant
      output patterns, suggesting a role in toggling output between signaling states.

PMID- 18621897
TI  - Identification of a sigma B-dependent small noncoding RNA in Listeria
      monocytogenes.
AB  - In Listeria monocytogenes, the alternative sigma factor sigma(B) plays important
      roles in stress tolerance and virulence. Here, we present the identification of
      SbrA, a novel small noncoding RNA that is produced in a sigma(B)-dependent
      manner. This finding adds the sigma(B) regulon to the growing list of stress
      induced regulatory circuits that include small noncoding RNAs.

PMID- 18621898
TI  - Excess SeqA leads to replication arrest and a cell division defect in Vibrio
      cholerae.
AB  - Although most bacteria contain a single circular chromosome, some have complex
      genomes, and all Vibrio species studied so far contain both a large and a small
      chromosome. In recent years, the divided genome of Vibrio cholerae has proven to
      be an interesting model system with both parallels to and novel features compared
      with the genome of Escherichia coli. While factors influencing the replication
      and segregation of both chromosomes have begun to be elucidated, much remains to
      be learned about the maintenance of this genome and of complex bacterial genomes
      generally. An important aspect of replicating any genome is the correct timing of
      initiation, without which organisms risk aneuploidy. During DNA replication in E.
      coli, newly replicated origins cannot immediately reinitiate because they undergo
      sequestration by the SeqA protein, which binds hemimethylated origin DNA. This
      DNA is already methylated by Dam on the template strand and later becomes fully
      methylated; aberrant amounts of Dam or the deletion of seqA leads to asynchronous
      replication. In our study, hemimethylated DNA was detected at both origins of V.
      cholerae, suggesting that these origins are also subject to sequestration. The
      overproduction of SeqA led to a loss of viability, the condensation of DNA, and a
      filamentous morphology. Cells with abnormal DNA content arose in the population,
      and replication was inhibited as determined by a reduced ratio of origin to
      terminus DNA in SeqA-overexpressing cells. Thus, excessive SeqA negatively
      affects replication in V. cholerae and prevents correct progression to downstream
      cell cycle events such as segregation and cell division.

PMID- 18621899
TI  - Salmonella enterica serovar gallinarum requires ppGpp for internalization and
      survival in animal cells.
AB  - To elucidate the pathogenic mechanism of Salmonella enterica serovar Gallinarum,
      we examined the expression of the genes encoded primarily in Salmonella
      pathogenicity island 1 (SPI-1) and SPI-2. These genes were found to be induced as
      cultures entered stationary phase under high- and low-oxygen growth conditions,
      as also observed for Salmonella serovar Typhimurium. In contrast, Salmonella
      serovar Gallinarum in the exponential growth phase most efficiently internalized
      cultured animal cells. Analysis of mutants defective in SPI-1 genes, SPI-2 genes,
      and others implicated in early stages of infection revealed that SPI-1 genes were
      not involved in the internalization of animal cells by Salmonella serovar
      Gallinarum. Following entry, however, Salmonella serovar Gallinarum was found to
      reside in LAMP1-positive vacuoles in both phagocytic and nonphagocytic cells,
      although internalization was independent of SPI-1. A mutation that conferred
      defects in ppGpp synthesis was the only one found to affect animal cell
      internalization by Salmonella serovar Gallinarum. It was concluded that
      Salmonella serovar Gallinarum internalizes animal cells by a mechanism
      independent of SPI-1 genes but dependent on ppGpp. Intracellular growth also
      required ppGpp for the transcription of genes encoded in SPI-2.

PMID- 18621900
TI  - Artificial septal targeting of Bacillus subtilis cell division proteins in
      Escherichia coli: an interspecies approach to the study of protein-protein
      interactions in multiprotein complexes.
AB  - Bacterial cell division is mediated by a set of proteins that assemble to form a
      large multiprotein complex called the divisome. Recent studies in Bacillus
      subtilis and Escherichia coli indicate that cell division proteins are involved
      in multiple cooperative binding interactions, thus presenting a technical
      challenge to the analysis of these interactions. We report here the use of an E.
      coli artificial septal targeting system for examining the interactions between
      the B. subtilis cell division proteins DivIB, FtsL, DivIC, and PBP 2B. This
      technique involves the fusion of one of the proteins (the "bait") to ZapA, an E.
      coli protein targeted to mid-cell, and the fusion of a second potentially
      interacting partner (the "prey") to green fluorescent protein (GFP). A positive
      interaction between two test proteins in E. coli leads to septal localization of
      the GFP fusion construct, which can be detected by fluorescence microscopy. Using
      this system, we present evidence for two sets of strong protein-protein
      interactions between B. subtilis divisomal proteins in E. coli, namely, DivIC
      with FtsL and DivIB with PBP 2B, that are independent of other B. subtilis cell
      division proteins and that do not disturb the cytokinesis process in the host
      cell. Our studies based on the coexpression of three or four of these B. subtilis
      cell division proteins suggest that interactions among these four proteins are
      not strong enough to allow the formation of a stable four-protein complex in E.
      coli in contrast to previous suggestions. Finally, our results demonstrate that
      E. coli artificial septal targeting is an efficient and alternative approach for
      detecting and characterizing stable protein-protein interactions within
      multiprotein complexes from other microorganisms. A salient feature of our
      approach is that it probably only detects the strongest interactions, thus giving
      an indication of whether some interactions suggested by other techniques may
      either be considerably weaker or due to false positives.

PMID- 18621901
TI  - Determination of antibiotic hypersensitivity among 4,000 single-gene-knockout
      mutants of Escherichia coli.
AB  - We have tested the entire Keio collection of close to 4,000 single-gene knockouts
      in Escherichia coli for increased susceptibility to one of seven different
      antibiotics (ciprofloxacin, rifampin, vancomycin, ampicillin, sulfamethoxazole,
      gentamicin, or metronidazole). We used high-throughput screening of several
      subinhibitory concentrations of each antibiotic and reduced more than 65,000 data
      points to a set of 140 strains that display significantly increased sensitivities
      to at least one of the antibiotics, determining the MIC in each case. These data
      provide targets for the design of "codrugs" that can potentiate existing
      antibiotics. We have made a number of double mutants with greatly increased
      sensitivity to ciprofloxacin, and these overcome the resistance generated by
      certain gyrA mutations. Many of the gene knockouts in E. coli are hypersensitive
      to more than one antibiotic. Together, all of these data allow us to outline the
      cell's "intrinsic resistome," which provides innate resistance to antibiotics.

PMID- 18621902
TI  - Characterization of an inducible, antibiotic-resistant aminoacyl-tRNA synthetase
      gene in Streptomyces coelicolor.
AB  - Streptomyces coelicolor has two genes encoding tryptophanyl-tRNA synthetases, one
      of which (trpRS1) is resistant to and transcriptionally activated by indolmycin.
      We found that this gene also confers resistance to chuangxinmycin (another
      antibiotic that inhibits bacterial tryptophanyl-tRNA synthetases) and that its
      transcription is not absolutely dependent on either antibiotic.

PMID- 18621903
TI  - Membrane morphology and leukotoxin secretion are associated with a novel membrane
      protein of Aggregatibacter actinomycetemcomitans.
AB  - Gram-negative bacteria display either a flat or an irregular outer membrane. The
      periodontal pathogen Aggregatibacter (Actinobacillus) actinomycetemcomitans has
      an irregular outer membrane. We have identified a gene that is associated with
      the biogenesis of this morphology. The gene is part of a three-gene operon and
      codes for a 141-kDa protein designated morphogenesis protein C (MorC), which is
      conserved in several gram-negative bacteria including Haemophilus influenzae and
      Pasteurella multocida. Insertional inactivation of this gene resulted in the
      conversion of an irregularly shaped membrane to a flat membrane. Associated with
      this morphological change were the autoaggregation of the bacteria during
      planktonic growth and a concomitant increase in the surface hydrophobicity of the
      bacterium. The absence of MorC also resulted in the loss of the secretion of
      leukotoxin but not the ltxA transcription. Our findings suggest that MorC is
      critical for membrane morphology and leukotoxin secretion in A.
      actinomycetemcomitans.

PMID- 18621904
TI  - Different pathways of choline metabolism in two choline-independent strains of
      Streptococcus pneumoniae and their impact on virulence.
AB  - The two recently characterized Streptococcus pneumoniae strains--R6Chi and R6Cho(
      )--that have lost the unique auxotrophic requirement of this bacterial species
      for choline differ in their mechanisms of choline independence. In strain R6Chi
      the mechanism is caused by a point mutation in tacF, a gene that is part of the
      pneumococcal lic2 operon, which is essential for growth and survival of the
      bacteria. Cultures of lic2 mutants of the encapsulated strain D39Chi growing in
      choline-containing medium formed long chains, did not autolyze, had no choline in
      their cell wall, and were completely avirulent in the mouse intraperitoneal
      model. In contrast, while the Cho(-) strain carried a complete pneumococcal lic2
      operon and had no mutations in the tacF gene, deletion of the entire lic2 operon
      had no effect on the growth or phenotype of strain Cho(-). These observations
      suggest that the biochemical functions normally dependent on determinants of the
      pneumococcal lic2 operon may also be carried out in strain Cho(-) by a second set
      of genetic elements imported from Streptococcus oralis, the choline-independent
      streptococcal strain that served as the DNA donor in the heterologous
      transformation event that produced strain R6Cho(-). The identification in R6Cho(
      ) of a large (20-kb) S. oralis DNA insert carrying both tacF and licD genes
      confirms this prediction and suggests that these heterologous elements may
      represent a "backup" system capable of catalyzing P-choline incorporation and
      export of teichoic acid chains under conditions in which the native lic2 operon
      is not functional.

PMID- 18621905
TI  - Salmonella enterica serovar Typhimurium BipA exhibits two distinct ribosome
      binding modes.
AB  - BipA is a highly conserved prokaryotic GTPase that functions to influence
      numerous cellular processes in bacteria. In Escherichia coli and Salmonella
      enterica serovar Typhimurium, BipA has been implicated in controlling bacterial
      motility, modulating attachment and effacement processes, and upregulating the
      expression of virulence genes and is also responsible for avoidance of host
      defense mechanisms. In addition, BipA is thought to be involved in bacterial
      stress responses, such as those associated with virulence, temperature, and
      symbiosis. Thus, BipA is necessary for securing bacterial survival and successful
      invasion of the host. Steady-state kinetic analysis and pelleting assays were
      used to assess the GTPase and ribosome-binding properties of S. enterica BipA.
      Under normal bacterial growth, BipA associates with the ribosome in the GTP-bound
      state. However, using sucrose density gradients, we demonstrate that the
      association of BipA and the ribosome is altered under stress conditions in
      bacteria similar to those experienced during virulence. The data show that this
      differential binding is brought about by the presence of ppGpp, an alarmone that
      signals the onset of stress-related events in bacteria.

PMID- 18621906
TI  - Chronic intrauterine pulmonary hypertension increases endothelial cell Rho kinase
      activity and impairs angiogenesis in vitro.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is characterized by
      endothelial dysfunction and decreased vascular growth. The role of Rho kinase
      activity in modulating endothelial function and regulating angiogenesis during
      normal lung development and in PPHN is unknown. We hypothesized that PPHN
      increases Rho kinase activity in fetal pulmonary artery endothelial cells (PAECs)
      and impairs angiogenesis in vitro. Proximal PAECs were harvested from fetal sheep
      with partial ligation of the ductus arteriosus in utero (PPHN) and age-matched
      controls. Rho kinase activity was measured by RhoA, Rho GTP, and phosphorylated
      MYPT-1 protein content. The effects of Rho kinase activity on angiogenesis,
      endothelial nitric oxide (NO) synthase (eNOS) protein expression, and NO
      production were determined in normal and PPHN PAECs. Angiogenesis was assessed by
      tube formation in vitro with/without Y-27632 (a Rho kinase inhibitor) and
      calpeptin (a Rho kinase activator) in the presence/absence of N-nitro-l-arginine
      (l-NA, an NOS inhibitor). RhoA, Rho GTP, and phosphorylated MYPT-1 protein were
      increased in PPHN PAECs. Tube formation was reduced 29% in PPHN PAECs (P < 0.001)
      and increased with Y-27632 treatment in normal and PPHN PAECs, with PPHN PAECs
      achieving levels similar to those of normal PAECs. l-NA inhibited the Y-27632
      induced increase in tube formation in normal, but not PPHN, PAECs. Calpeptin
      reduced tube formation in normal and PPHN PAECs. eNOS expression was reduced 42%
      in PPHN PAECs (P < 0.01). Y-27632 increased eNOS protein and NO production in
      normal and PPHN PAECs. Calpeptin decreased eNOS protein only in normal PAECs but
      reduced NO production in normal and PPHN PAECs. We conclude that Rho kinase
      activity is increased in PPHN PAECs and impairs angiogenesis and downregulates
      eNOS protein and NO production in vitro.

PMID- 18621907
TI  - Cytokine-induced arginase activity in pulmonary endothelial cells is dependent on
      Src family tyrosine kinase activity.
AB  - We hypothesized that the Src family tyrosine kinases (STKs) are involved in the
      upregulation of arginase and inducible nitric oxide synthase (iNOS) expression in
      response to inflammatory stimuli in pulmonary endothelial cells. Treatment of
      bovine pulmonary arterial endothelial cells (bPAEC) with lipopolysaccharide and
      tumor necrosis factor-alpha (L/T) resulted in increased urea and nitric oxide
      (NO) production, and this increase in urea and NO production was inhibited by the
      STK inhibitor PP1 (10 microM). The STK inhibitors PP2 (10 microM) and herbimycin
      A (10 microM) also prevented the L/T-induced expression of both arginase II and
      iNOS mRNA in bPAEC. Together, the data demonstrate a central role of STK in the
      upregulation of both arginase II and iNOS in bPAEC in response to L/T treatment.
      To identify the specific kinase(s) required for the induction of urea and NO
      production, we studied human pulmonary microvascular endothelial cells (hPMVEC)
      so that short interfering RNA (siRNA) techniques could be employed. We found that
      hPMVEC express Fyn, Yes, c-Src, Lyn, and Blk and that the protein expression of
      Fyn, Yes, c-Src, and Lyn could be inhibited with specific siRNA. The siRNA
      targeting Fyn prevented the cytokine-induced increase in urea and NO production,
      whereas siRNAs specifically targeting Yes, c-Src, and Lyn had no appreciable
      effect on cytokine-induced urea and NO production. These findings support our
      hypothesis that inflammatory stimuli lead to increased urea and NO production
      through a STK-mediated pathway. Furthermore, these results indicate that the STK
      Fyn plays a critical role in this process.

PMID- 18621908
TI  - Alveolar epithelial cell injury with Epstein-Barr virus upregulates TGFbeta1
      expression.
AB  - Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung
      disease characterized by alveolar epithelial cells apoptosis, fibroblast
      proliferation, and ECM protein deposition. Epstein-Barr virus (EBV) has
      previously been localized to alveolar epithelial cells of IPF patients and is
      associated with a poor prognosis. In this study, we utilized a microarray-based
      differential gene expression analysis strategy to identify molecular drivers of
      EBV-associated lung fibrosis. Two cell lines, primary human alveolar epithelial
      cells type 2 and A549 cells, were infected with EBV. EBV lytic phase induction
      increased active and total transforming growth factor-beta1 (TGFbeta1) transcript
      expression in association with reduced cell proliferation and increased caspase
      3/7 activity. Exposing EBV-infected cells to ganciclovir resulted in TGFbeta1
      deregulation and reduced expression of EBV early response genes, BRLF1 and BZLF1.
      We targeted the BRLF1 and BZLF1 gene products, Rta and Zta, by silencing RNA, and
      this resulted in the normalization of TGFbeta1 transcript and cell proliferation
      levels. Our study using a viral cell line model complements existing human and
      animal model data and further provides evidence to suggest that viral epithelial
      cell injury may play a role in IPF.

PMID- 18621910
TI  - Innate immune responses in murine pleural mesothelial cells: Toll-like receptor-2
      dependent induction of beta-defensin-2 by staphylococcal peptidoglycan.
AB  - The innate immune response is mediated in part by pattern recognition receptors
      including Toll-like receptors (TLRs). The pleural mesothelial cells (PMCs) that
      line the pleural surface are in direct contact with pleural fluid and accordingly
      carry the risk of exposure to infiltrating microorganisms or their components in
      an event of a complicated parapneumonic effusion. Here we show that murine
      primary PMCs constitutively express TLR-1 through TLR-9 and, upon activation with
      peptidoglycan (PGN), mouse PMC produce antimicrobial peptide beta-defensin-2 (mBD
      2). Treatment of PMCs with staphylococcal PGN, a gram-positive bacterial cell
      wall component and a TLR-2 agonist, resulted in a significant increase in TLR-2
      and mBD-2 expression. Silencing of TLR-2 expression by small interfering RNA led
      to the downregulation of PGN-induced mBD-2 expression, thereby establishing
      causal relationship between the activation of TLR-2 receptor and mBD-2
      production. PMCs exposed to PGN showed increased p38 MAPK activity. In addition,
      PGN-induced mBD-2 expression was attenuated by SB203580, a p38 MAPK inhibitor,
      underlining the importance of p38 MAPK in mBD-2 induction. Inhibition of
      erk1/erk2 or phosphatidylinositol 3-kinase did not block PGN-induced mBD-2
      expression in PMC. PGN-activated PMC-derived mBD-2 significantly killed
      Staphylococcus aureus, and mBD-2-neutralizing antibodies blunted this
      antimicrobial activity. Taken together, these data indicate that PMCs may
      contribute to host innate immune defense upon exposure to gram-positive bacteria
      or their products within the pleural space by upregulating TLR-2 and mBD-2
      expression.

PMID- 18621909
TI  - Reactive oxygen species mediate RhoA/Rho kinase-induced Ca2+ sensitization in
      pulmonary vascular smooth muscle following chronic hypoxia.
AB  - Recent evidence supports a prominent role for Rho kinase (ROK)-mediated pulmonary
      vasoconstriction in the development and maintenance of chronic hypoxia (CH)
      induced pulmonary hypertension. Endothelin (ET)-1 contributes to the pulmonary
      hypertensive response to CH, and recent studies by our laboratory and others
      indicate that pulmonary vascular reactivity following CH is largely independent
      of changes in vascular smooth muscle (VSM) intracellular free calcium
      concentration ([Ca(2+)](i)). In addition, CH increases generation of reactive
      oxygen species (ROS) in pulmonary arteries, which may underlie the shift toward
      ROK-dependent Ca(2+) sensitization. Therefore, we hypothesized that ROS-dependent
      RhoA/ROK signaling mediates ET-1-induced Ca(2+) sensitization in pulmonary VSM
      following CH. To test this hypothesis, we determined the effect of
      pharmacological inhibitors of ROK, myosin light chain kinase (MLCK), tyrosine
      kinase (TK), and PKC on ET-1-induced vasoconstriction in endothelium-denuded,
      Ca(2+)-permeabilized small pulmonary arteries from control and CH (4 wk at 0.5
      atm) rats. Further experiments examined ET-1-mediated, ROK-dependent
      phosphorylation of the regulatory subunit of myosin light chain phosphatase
      (MLCP), MYPT1. Finally, we measured ET-1-induced ROS generation in
      dihydroethidium-loaded small pulmonary arteries and investigated the role of ROS
      in mediating ET-1-induced, RhoA/ROK-dependent Ca(2+) sensitization using the
      superoxide anion scavenger, tiron. We found that CH increases ET-1-induced Ca(2+)
      sensitization that is sensitive to inhibition of ROK and MLCK, but not PKC or TK,
      and correlates with ROK-dependent MYPT1(Thr696) phosphorylation. Furthermore,
      tiron inhibited basal and ET-1-stimulated ROS generation, RhoA activation, and
      VSM Ca(2+) sensitization following CH. We conclude that CH augments ET-1-induced
      Ca(2+) sensitization through ROS-dependent activation of RhoA/ROK signaling in
      pulmonary VSM.

PMID- 18621911
TI  - Phospholipase D signaling in serotonin-induced mitogenesis of pulmonary artery
      smooth muscle cells.
AB  - We have previously reported the participation of mitogen-activated protein, Rho,
      and phosphoinositide-3 (PI3) kinases in separate pathways in serotonin (5-HT)
      induced proliferation of pulmonary artery smooth muscle cells (SMCs). In this
      study, we investigated the possible participation of phospholipase D (PLD) and
      phosphatidic acid (PA) in this growth process. 5-HT stimulated a time-dependent
      increase in [(3)H]phosphatidylbutanol and PA generation. Exposure of SMCs to 1
      butanol or overexpression of an inactive mutant of human PLD1R898R blocked 5-HT
      induced proliferation. Furthermore, 1-butanol inhibited 5-HT activation of S6K1
      and S6 protein, downstream effectors of mammalian target of rapamycin (mTOR), by
      80 and 72%, respectively, and partially blocked activation of extracellular
      signal-regulated kinase (ERK) by 30% but had no effect on other associated
      signaling pathways. Exogenous PA caused cellular proliferation and revitalized
      cyclin D1 expression by 5-HT of the 1-butanol-treated cells. PA also reproduced
      activations by 5-HT of mTOR, S6K1, and ERK. Transfection with inactive human PLD1
      reduced 5-HT-induced activation of S6K1 by approximately 50%. Inhibition of 5-HT
      receptor 2A (R 2A) with ketaserin blocked PLD activation by 5-HT. Inhibition with
      PI3-kinase inhibitor failed to block either activation of PLD by 5-HT or PA
      dependent S6K1 phosphorylation. Taken together, these results indicate that
      ligation of the 5-HTR 2A by 5-HT initiates PLD activation in SMCs, and that its
      product, PA, is an early signaling molecule in 5-HT-induced pulmonary artery SMC
      proliferation. Signaling by PA produces its downstream effects primarily through
      the mTOR/S6K1 pathway and to a lesser extent through the ERK pathway. Hydrolysis
      of cell membrane lipid may be important in vascular effects of 5-HT.

PMID- 18621913
TI  - The novel p53 isoform "delta p53" is a misfolded protein and does not bind the
      p21 promoter site.
AB  - The tumor suppressor p53 can be expressed as different isoforms because of
      promoter selection and mRNA editing. One isoform, "delta p53" (Delta p53),
      results from what would be an unusual alternative splicing of exons 7/8 of the
      p53 gene, conserving the reading frame and generating a novel protein with
      proposed transcriptional activity essential for the intra S-phase checkpoint.
      Here, we show that the deletion of the 66 residues that correspond to strand
      beta10 and the C-terminal helix of the core domain and the interconnecting linker
      to the tetramerization domain occurring in the Delta p53 isoform leads to a
      misfolded and unstable protein, prone to form soluble aggregates, which does not
      bind the p21 promoter site. The complex of coexpressed Delta p53 and flp53 is
      soluble in vitro and binds poorly to DNA. Our results provide a structural
      explanation for the dominant-negative effect of Delta p53 and its lack of
      transcriptional activity.

PMID- 18621914
TI  - The hemoglobins of the trematodes Fasciola hepatica and Paramphistomum epiclitum:
      a molecular biological, physico-chemical, kinetic, and vaccination study.
AB  - The trematode Fasciola hepatica (Fa.he.) is a common parasite of human and
      livestock. The hemoglobin (Hb) of Fa.he., a potential immunogen, was chosen for
      characterization in the search for an effective vaccine. Characterization of
      trematode Hbs show that they are intracellular single-domain globins with the
      following remarkable features: (1) Fa.he. expresses two Hb isoforms that differ
      at two amino acid sites (F1: 119Y/123Q; F2: 119F/123L). Both isoforms are
      monoacetylated at their N-termini; (2) the genes coding for Fa.he. and
      Paramphistomum epiclitum (Pa.ep.) Hbs are interrupted by two introns at the
      conserved positions B12.2 and G7.0.; (3) UV/VIS and resonance Raman spectroscopy
      identify the recombinant Fa.he. HbF2 as a pentacoordinated high-spin ferrous Hb;
      (4) electron paramagnetic resonance spectroscopy of cyano-met Fa.he. HbF2 proves
      that the endogenously bound imidazole has no imidazolate character; (5) the major
      structural determinants of the globin fold are present, they contain a
      TyrB10/TyrE7 residue pair on the distal side. Although such distal-site pair is a
      signature for high oxygen affinity, as shown for Pa.ep. Hb, the oxygen-binding
      rate parameters for Fa.he. Hb are intermediate between those of myoglobin and
      those of other trematode Hbs; (6) the three-dimensional structure of recombinant
      Fa.he. HbF2 from this study closely resembles the three-dimensional structure of
      Pa.ep. determined earlier. The set of distal-site polar interactions observed in
      Pa.ep. Hb is matched with small but significant structural adjustments; (7)
      despite the potential immunogenic character of the fluke Hb, vaccination of
      calves with recombinant Fa.he. HbF2 failed to promote protection against
      parasitic infection.

PMID- 18621915
TI  - A universal method for fishing target proteins from mixtures of biomolecules
      using isothermal titration calorimetry.
AB  - The most challenging tasks in biology include the identification of (1) the
      orphan receptor for a ligand, (2) the ligand for an orphan receptor protein, and
      (3) the target protein(s) for a given drug or a lead compound that are critical
      for the pharmacological or side effects. At present, several approaches are
      available, including cell- or animal-based assays, affinity labeling, solid-phase
      binding assays, surface plasmon resonance, and nuclear magnetic resonance. Most
      of these techniques are not easy to apply when the target protein is unknown and
      the compound is not amenable to labeling, chemical modification, or
      immobilization. Here we demonstrate a new universal method for fishing orphan
      target proteins from a complex mixture of biomolecules using isothermal titration
      calorimetry (ITC) as a tracking tool. We took snake venom, a crude mixture of
      several hundred proteins/peptides, as a model to demonstrate our proposed ITC
      method in tracking the isolation and purification of two distinct target
      proteins, a major component and a minor component. Identities of fished out
      target proteins were confirmed by amino acid sequencing and inhibition assays.
      This method has the potential to make a significant advancement in the area of
      identifying orphan target proteins and inhibitor screening in drug discovery and
      characterization.

PMID- 18621916
TI  - A study of indoor radon levels in rural dwellings of Ezine (Canakkale, Turkey)
      using solid-state nuclear track detectors.
AB  - Indoor radon activity level and radon effective dose (ED) rate have been carried
      out in the rural dwellings of Ezine (Canakkale) during the summer season using
      Radosys-2000, a complete set suitable to radon concentration measurements with CR
      39 plastic alpha track detectors. The range of radon concentration varied between
      9 and 300 Bq m(-3), with an average of 67.9 (39.9 SD) Bq m(-3). Assuming an
      indoor occupancy factor of 0.8 and 0.4 for the equilibrium factor of radon
      indoors, it has been found that the 222Rn ED rate in the dwellings studied ranges
      from 0.4 to 5.2 mSv y(-1), with an average value of 1.7 (1.0) mSv y(-1). There is
      a possibility that low radon concentrations exist indoors during the summer
      season in the study area because of relatively high ventilation rates in the
      dwellings. A winter survey will be needed for future estimation of the annual ED.

PMID- 18621912
TI  - Animal models of acute lung injury.
AB  - Acute lung injury in humans is characterized histopathologically by neutrophilic
      alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane
      formation, and microvascular thrombi. Different animal models of experimental
      lung injury have been used to investigate mechanisms of lung injury. Most are
      based on reproducing in animals known risk factors for ARDS, such as sepsis,
      lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion
      of pulmonary or distal vascular beds, and other clinical risks. However, none of
      these models fully reproduces the features of human lung injury. The goal of this
      review is to summarize the strengths and weaknesses of existing models of lung
      injury. We review the specific features of human ARDS that should be modeled in
      experimental lung injury and then discuss specific characteristics of animal
      species that may affect the pulmonary host response to noxious stimuli. We
      emphasize those models of lung injury that are based on reproducing risk factors
      for human ARDS in animals and discuss the advantages and disadvantages of each
      model and the extent to which each model reproduces human ARDS. The present
      review will help guide investigators in the design and interpretation of animal
      studies of acute lung injury.

PMID- 18621917
TI  - Comparison of radiation dose to patient and staff for two interventional
      cardiology units: a phantom study.
AB  - The purpose of this investigation was to measure the patient and staff dose
      during routine interventional cardiology procedures for an image intensifier
      based and a flat detector system using a water phantom. The Integris BH3000 image
      intensifier-based (Philips) and the Axiom Artis flat detector-based (Siemens)
      angiography units were used in this study. The accuracy of tubes potential and
      irradiation timers and also internal dosimeters were verified and confirmed. A
      water phantom with a thickness of 18 cm was used for patient and staff dose
      measurements. For the Philips system, phantom entrance dose rates were 2.77 and
      38.97 microGym(2) s(-1) during fluoroscopy and cineangiography. The respective
      dose rates for the Siemens were 1.98 and 13.46 microGym(2) s(-1). Phantom
      entrance dose rate was 28.5 and 65% higher for the Philips system during
      fluoroscopy and cineangiography, respectively. Comparing the scattered dose rates
      at the operator location showed that the flat detector-based Siemens system
      delivers five times lower dose to the operator in comparison with the image
      intensifier-based Philips unit. The results suggest that the decrease in received
      dose of the patient and staff is achievable using the flat detector system. In
      addition, application of lead curtain and glass is recommended to lower the
      cardiologist dose especially for the image intensifier-based Philips system.

PMID- 18621918
TI  - Statistical approaches to forecast gamma dose rates by using measurements from
      the atmosphere.
AB  - In this paper, the results obtained by inter-comparing several statistical
      techniques for estimating gamma dose rates, such as an exponential moving average
      model, a seasonal exponential smoothing model and an artificial neural networks
      model, are reported. Seven years of gamma dose rates data measured in Daejeon
      City, Korea, were divided into two parts to develop the models and validate the
      effectiveness of the generated predictions by the techniques mentioned above.
      Artificial neural networks model shows the best forecasting capability among the
      three statistical models. The reason why the artificial neural networks model
      provides a superior prediction to the other models would be its ability for a non
      linear approximation. To replace the gamma dose rates when missing data for an
      environmental monitoring system occurs, the moving average model and the seasonal
      exponential smoothing model can be better because they are faster and easier for
      applicability than the artificial neural networks model. These kinds of
      statistical approaches will be helpful for a real-time control of radio emissions
      or for an environmental quality assessment.

PMID- 18621919
TI  - Long-term fade study of the DT-702 LiF: Mg,Cu,P TLD.
AB  - LiF thermoluminescent dosemeters (TLDs) are used by the US Navy to record
      radiation exposure of personnel. The Model DT-648 LiF:Mg,Ti TLD has been replaced
      by a new Model DT-702 LiF:Mg,Cu,P TLD. The DT-648 was used for many years and has
      undergone extensive testing to identify its pre- and post-irradiation fade
      operating characteristics. Studies have shown that the addition of copper
      increases the thermoluminesence sensitivity of the TLD for improved low-level
      radiation monitoring. This study evaluates various fading characteristics of the
      new copper-doped dosemeter using current equipment for processing of TLDs and
      calibrating to a National Institute of Standards and Technology standard source.
      The 57-week study took place at the Naval Dosimetry Center, Bethesda, MD, USA.
      TLDs were stored for various lengths of time before and after being exposed to a
      National Institute of Standards and Technology calibrated radiation sources. TLDs
      were then processed using current US Navy instructions and the resulting dose
      compared with the calibrated exposure. Both loss of signal and loss of
      sensitivity were evaluated. The results of this study have shown that the DT-702
      TLD has no statistically significant change in sensitivity or change in signal
      with up to 57 weeks of pre- or post-irradiation time. The results of this study
      will increase the accuracy of exposure record keeping for the Navy and will allow
      longer issue periods. This will increase flexibility with international and
      domestic shipping procedures, as well as reduce workload requirements for
      dosimetry processing.

PMID- 18621920
TI  - Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher
      affinity than human apoA-I.
AB  - 4F is an anti-inflammatory, apolipoprotein A-I (apoA-I)-mimetic peptide that is
      active in vivo at nanomolar concentrations in the presence of a large molar
      excess of apoA-I. Physiologic concentrations ( approximately 35 microM) of human
      apoA-I did not inhibit the production of LDL-induced monocyte chemotactic
      activity by human aortic endothelial cell cultures, but adding nanomolar
      concentrations of 4F in the presence of approximately 35 microM apoA-I
      significantly reduced this inflammatory response. We analyzed lipid binding by
      surface plasmon resonance. The anti-inflammatory 4F peptide bound oxidized lipids
      with much higher affinity than did apoA-I. Initially, we examined the binding of
      PAPC (1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine) and observed
      that its oxidized products bound 4F with an affinity that was approximately 4-6
      orders of magnitude higher than that of apoA-I. This high binding affinity was
      confirmed in studies with defined lipids and phospholipids. 3F-2 and 3F(14) are
      also amphipathic alpha-helical octadecapeptides, but 3F-2 inhibits
      atherosclerosis in mice and 3F(14) does not. Like 4F, 3F-2 also bound oxidized
      phospholipids with very high affinity, whereas 3F(14) resembled apoA-I. The
      extraordinary ability of 4F to bind pro-inflammatory oxidized lipids probably
      accounts for its remarkable anti-inflammatory properties.

PMID- 18621921
TI  - Identification and spatial distribution of glycine receptor subunits in human
      sperm.
AB  - The human sperm surface glycine receptor (GLR) plays a role in an important
      fertilization event, the sperm acrosome reaction. Here, by western blot analysis,
      we report the presence of GLRA1, GLRA2, GLRA3, and GLRB subunits in human sperm.
      Immunolocalization studies showed that the GLRA1 and GLRA2 subunits are present
      in the equatorial region, the GLRA3 subunit in the flagellar principal piece, and
      the GLRB subunit in the acrosomal region of sperm. This first demonstration of
      isoforms of the sperm GLRA subunit and of a differential spatial distribution of
      the alpha and beta subunits on the surface of mammalian sperm suggests the
      possibility that human sperm GLRs have more than one function.

PMID- 18621922
TI  - Molecular phylogenetic analysis of a geographically and temporally matched set of
      Candida albicans isolates from humans and nonmigratory wildlife in central
      Illinois.
AB  - This study explored whether wildlife species serve as the reservoir for human
      Candida albicans strains in a given geographic area. C. albicans isolates were
      collected from nonmigratory wildlife admitted to the University of Illinois
      Wildlife Medical Clinic. A geographically and temporally matched set of C.
      albicans oral isolates was collected from healthy human volunteers. Multilocus
      sequence typing was used to assign strains to genetic clades. Clade 1 isolates,
      particularly diploid sequence type 69 (DST 69), were most common in humans. Clade
      1 strains were less frequently recovered from wildlife, while clade 8 strains,
      particularly DST 90, were overrepresented in the wildlife collection. All
      instances where a wildlife and human isolate shared the same DST occurred within
      clade 1. Clade distributions between human and wildlife isolates were
      significantly different, demonstrating population isolation between the groups.
      These differences may indicate limited strain transfer between groups or
      differential selection of C. albicans isolates in humans and wildlife. Wildlife
      strains had an amphotericin B MIC significantly lower than that of human
      isolates; strains with increased susceptibility were from several clades. C.
      albicans isolates were collected from domestic animals to provide comparisons
      with human and wildlife data sets. C. albicans isolation from canine and feline
      oral and anal swabs was infrequent; companion animal isolates were closely
      related to clade 1 human isolates. Collectively, the data suggest a greater
      likelihood of C. albicans transfer from humans to animals than from animals to
      humans. The nontransient human population may maintain the connection between
      geography and the C. albicans genetic groups recovered from humans.

PMID- 18621923
TI  - Polo-like kinase is expressed in S/G2/M phase and associated with the flagellum
      attachment zone in both procyclic and bloodstream forms of Trypanosoma brucei.
AB  - Trypanosoma brucei, the etiologic agent of African sleeping sickness, divides
      into insect (procyclic) and bloodstream forms. These two forms are subject to
      distinct cell cycle regulations, with cytokinesis controlled primarily by basal
      body/kinetoplast segregation in the procyclic form but by mitosis in the
      bloodstream form. Polo-like kinases (PLKs), known to play essential roles in
      regulating both mitosis and cytokinesis among eukaryotes, have a homologue in T.
      brucei, TbPLK, which regulates only cytokinesis. In our previous study,
      overexpressed triply hemagglutinin-tagged TbPLK (TbPLK-3HA) in the procyclic form
      localized to a mid-dorsal point and the anterior tip of the cell along the
      flagellum attachment zone (FAZ). In our current study, TbPLK-3HA expressed at the
      endogenous level was identified at the same dorsal location of both procyclic and
      bloodstream forms, albeit it was no longer detectable at the anterior tip of the
      cell. Endogenously expressed TbPLK fused with an enhanced yellow fluorescent
      protein (EYFP) localized to the same dorsal location along the FAZs in living
      procyclic and bloodstream cells. Fluorescence-activated cell sorter analysis of
      hydroxyurea-synchronized procyclic cells revealed that TbPLK-EYFP emerges during
      S phase, persists through G(2)/M phase, and vanishes in G(1) phase. An indicated
      TbPLK-EYFP association with the FAZs of G(2)/M cells may thus represent a timely
      localization to a potential initiation site of cytokinesis, which agrees with the
      recognized role of TbPLK in cytokinetic initiation.

PMID- 18621924
TI  - Regulation of the subcellular localization of cyclic AMP-dependent protein kinase
      in response to physiological stresses and sexual differentiation in the fission
      yeast Schizosaccharomyces pombe.
AB  - We describe regulation of the subcellular localization of cyclic AMP (cAMP)
      dependent protein kinase (PKA) regulatory (Cgs1p) and catalytic (Pka1p) subunits
      in the fission yeast Schizosaccharomyces pombe in response to physiological
      stresses and during sexual differentiation as determined by fluorescence
      microscopy of the Cgs1-green fluorescent protein (GFP) and Pka1-GFP fusion
      proteins, respectively. In wild-type S. pombe cells cultured to log phase under
      normal growth conditions, Cgs1p and Pka1p are concentrated in the nucleus and
      more diffusely present in the cytoplasm. Nuclear localization of both proteins is
      dependent on cAMP, since in cells lacking adenylate cyclase they are detectable
      only in the cytoplasm. In cells lacking Cgs1p or both Cgs1p and adenylate
      cyclase, Pka1p is concentrated in the nucleus, demonstrating a role for Cgs1p in
      the nuclear exclusion of Pka1p. Nuclear-cytoplasmic redistribution of Cgs1p and
      Pka1p is triggered by growth in glucose-limited or hyperosmotic media and in
      response to stationary-phase growth. In addition, both proteins are excluded from
      the nucleus in mating cells undergoing karyogamy and subsequently concentrated in
      postmeiotic spores. Cgs1p is required for subcellular redistribution of Pka1p
      induced by growth in glucose-limited and hyperosmotic media and during karyogamy
      but is not required for Pka1p redistribution triggered by stationary-phase growth
      or for the enrichment of Pka1p in spores. Our results demonstrate that PKA
      localization is regulated by cAMP and regulatory subunit-dependent and 
      independent mechanisms in S. pombe.

PMID- 18621925
TI  - Rho5p is involved in mediating the osmotic stress response in Saccharomyces
      cerevisiae, and its activity is regulated via Msi1p and Npr1p by phosphorylation
      and ubiquitination.
AB  - Small GTPases of the Rho family act as molecular switches, and modulation of the
      GTP-bound state of Rho proteins is a well-characterized means of regulating their
      signaling activity in vivo. In contrast, the regulation of Rho-type GTPases by
      posttranslational modifications is poorly understood. Here, we present evidence
      of the control of the Saccharomyces cerevisiae Rho-type GTPase Rho5p by
      phosphorylation and ubiquitination. Rho5p binds to Ste50p, and the expression of
      the activated RHO5(Q91H) allele in an Deltaste50 strain is lethal under
      conditions of osmotic stress. An overexpression screen identified RGD2 and MSI1
      as being high-copy suppressors of the osmotic sensitivity of this lethality.
      Rgd2p had been identified as being a possible Rho5p GTPase-activating protein
      based on an in vitro assay; this result supports its function as a regulator of
      Rho5p activity in vivo. MSI1 was previously identified as being a suppressor of
      hyperactive Ras/cyclic AMP signaling, where it antagonizes Npr1p kinase activity
      and promotes ubiquitination. Here, we show that Msi1p also acts via Npr1p to
      suppress activated Rho5p signaling. Rho5p is ubiquitinated, and its expression is
      lethal in a strain that is compromised for proteasome activity. These data
      identify Rho5p as being a target of Msi1p/Npr1p regulation and describe a
      regulatory circuit involving phosphorylation and ubiquitination.

PMID- 18621926
TI  - Investigation of the mechanisms underlying the differential effects of the K262R
      mutation of P450 2B6 on catalytic activity.
AB  - Human P450 2B6 is a polymorphic enzyme involved in the oxidative metabolism of a
      number of clinically relevant substrates. The lysine 262-to-arginine mutant of
      cytochrome P450 2B6 (P450 2B6.4) has been shown to have differential effects on
      P450 2B6 catalytic activity. We reported previously that the mutant enzyme was
      unable to metabolize 17-alpha-ethynylestradiol (17EE) or become inactivated by
      17EE or efavirenz, which are inactivators of the wild-type enzyme. Studies were
      performed to elucidate the mechanism by which this mutation affects P450 2B6
      catalytic activity. Studies using phenyldiazene to investigate differences
      between the active site topologies of the wild-type and mutant enzymes revealed
      only minor differences. Likewise, Ks values for the binding of both benzphetamine
      and efavirenz were comparable between the two enzymes. Using the alternate
      oxidant tert-butyl hydroperoxide, the mutant enzyme was inactivated by both 17EE
      and efavirenz. The stoichiometry of 17EE and efavirenz metabolism by P450s 2B6
      and 2B6.4 revealed that the mutant enzyme was more uncoupled, producing hydrogen
      peroxide as the primary product. Interestingly, the addition of cytochrome b5
      improved the coupling of the mutant, resulting in increased catalytic activity.
      In the presence of cytochrome b5 the variant readily metabolized 17EE and was
      inactivated by both 17EE and efavirenz. It is therefore proposed that the
      oxyferrous or iron-peroxo intermediate formed by the mutant enzyme in the
      presence of 17EE and efavirenz may be less stable than the same intermediates
      formed by the wild-type enzyme.

PMID- 18621927
TI  - Paraxanthine, the primary metabolite of caffeine, provides protection against
      dopaminergic cell death via stimulation of ryanodine receptor channels.
AB  - Epidemiological evidence suggests that caffeine or its metabolites reduce the
      risk of developing Parkinson's disease, possibly by protecting dopaminergic
      neurons, but the underlying mechanism is not clearly understood. Here, we show
      that the primary metabolite of caffeine, paraxanthine (PX; 1, 7
      dimethylxanthine), was strongly protective against neurodegeneration and loss of
      synaptic function in a culture system of selective dopaminergic cell death. In
      contrast, caffeine itself afforded only marginal protection. The survival effect
      of PX was highly specific to dopaminergic neurons and independent of glial cell
      line-derived neurotrophic factor (GDNF). Nevertheless, PX had the potential to
      rescue dopaminergic neurons that had matured initially with and were then
      deprived of GDNF. The protective effect of PX was not mediated by blockade of
      adenosine receptors or by elevation of intracellular cAMP levels, two
      pharmacological effects typical of methylxanthine derivatives. Instead, it was
      attributable to a moderate increase in free cytosolic calcium via the activation
      of reticulum endoplasmic ryanodine receptor (RyR) channels. Consistent with these
      observations, PX and also ryanodine, the preferential agonist of RyRs, were
      protective in an unrelated paradigm of mitochondrial toxin-induced dopaminergic
      cell death. In conclusion, our data suggest that PX has a neuroprotective
      potential for diseased dopaminergic neurons.

PMID- 18621928
TI  - A dose-ranging study evaluating once-daily oral administration of the factor Xa
      inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep
      vein thrombosis: the Einstein-DVT Dose-Ranging Study.
AB  - We performed a randomized dose-ranging study, double-blind for rivaroxaban doses
      and open-label for the comparator (low-molecular-weight heparin followed by
      vitamin K antagonists) to assess the optimal dose of rivaroxaban for the
      treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous
      thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator.
      Treatment lasted for 84 days. The primary efficacy outcome was the 3-month
      incidence of the composite of symptomatic venous thromboembolic complications and
      asymptomatic deterioration in thrombotic burden as assessed by comparison of
      ultrasound and perfusion lung scanning at day 84 with baseline. The main safety
      outcome was the composite of major bleeding and clinically relevant nonmajor
      bleeding. A total of 449 (83%) of the 543 patients could be included in the per
      protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and
      6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and
      in 9.9% of those receiving standard therapy. The main safety outcome occurred in
      5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups,
      respectively, and in 8.8% of those receiving standard therapy. These results with
      simple fixed-dose oral regimens justify phase 3 evaluations
      (www.ClinicalTrials.gov no.NCT00395772).

PMID- 18621929
TI  - A multicenter prospective phase 2 randomized study of extracorporeal
      photopheresis for treatment of chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is a major limitation of successful
      hematopoietic cell transplantation. The safety and efficacy of extracorporeal
      photopheresis (ECP) for 12 to 24 weeks together with standard therapy was
      compared with standard therapy alone in patients with cutaneous manifestations of
      cGVHD that could not be adequately controlled by corticosteroid treatment. The
      primary efficacy end point was a blinded quantitative comparison of percent
      change from baseline in Total Skin Score (TSS) of 10 body regions at week 12.
      Ninety-five patients were randomized to either ECP and standard therapy (n = 48)
      or standard therapy alone (n = 47). The median percentage improvement in TSS at
      week 12 was 14.5% for the ECP arm and 8.5% for the control arm (P = .48). The
      proportion of patients who had at least a 50% reduction in steroid dose and at
      least a 25% decrease from baseline in TSS was 8.3% in the ECP arm at week 12 and
      0% in the control arm (P = .04). The nonblinded investigator assessment of skin
      complete or partial responses revealed a significant improvement in favor of ECP
      (P < .001). ECP was generally well tolerated. These results suggest that ECP may
      have a steroid-sparing effect in the treatment of cGVHD. Clinical trials
      registered at www.ClinicalTrials.gov as NCT00054613.

PMID- 18621930
TI  - Translational control of c-MYC by rapamycin promotes terminal myeloid
      differentiation.
AB  - c-MYC inhibits differentiation and regulates the process by which cells acquire
      biomass, cell growth. Down-regulation of c-MYC, reduced cell growth, and
      decreased activity of the PI3K/AKT/mTORC1 signal transduction pathway are
      features of the terminal differentiation of committed myeloid precursors to
      polymorphonuclear neutrophils. Since mTORC1 regulates growth, we hypothesized
      that pharmacological inhibition of mTORC1 by rapamycin may reverse the phenotypic
      effects of c-MYC. Here we show that granulocytes blocked in their ability to
      differentiate by enforced expression of c-MYC can be induced to differentiate by
      reducing exogenous c-MYC expression through rapamycin treatment. Rapamycin also
      reduced expression of endogenous c-MYC and resulted in enhanced retinoid-induced
      differentiation. Total cellular c-Myc mRNA and c-MYC protein stability were
      unchanged by rapamycin, however the amount of c-Myc mRNA associated with
      polysomes was reduced. Therefore rapamycin limited expression of c-MYC by
      inhibiting c-Myc mRNA translation. These findings suggest that mTORC1 could be
      targeted to promote terminal differentiation in myeloid malignancies
      characterized by dysregulated expression of c-MYC.

PMID- 18621932
TI  - Looking toward DSM-V: should factitious disorder become a subtype of somatoform
      disorder?
AB  - BACKGROUND: Factitious and somatoform-disorder patients are alike in that they
      both organize their lives around seeking medical services in spite of having
      primarily a psychiatric condition. In DSM-IV, the key difference is that
      factitious-disorder patients feign illness, and somatoform-disorder patients
      actually believe they are ill. Although patients may not be conscious of their
      motivation or even their behaviors, deliberately embellishing history or inducing
      symptoms exemplifies behaviors designed to enhance a self-concept of being ill.
      CONCLUSION: For DSM-V, we propose reclassifying factitious disorder as a subtype
      within the somatoform-spectrum disorders or the proposed physical-symptom
      disorder, premised on our belief that deliberate deceptions serve primarily to
      portray to treaters the sense of being ill.

PMID- 18621933
TI  - Cancer fatigue: a neurobiological review for psychiatrists.
AB  - BACKGROUND: Fatigue, both during and subsequent to treatment, is a ubiquitous and
      debilitating phenomenon for patients undergoing treatment for cancer of all
      types. OBJECTIVE: This review will focus on understanding the complex
      neurobiological mechanisms underlying the phenomenon of cancer-related fatigue
      (CRF) and their relevance for various treatment routes. METHOD: The review will
      describe the prevalence of CRF, differential diagnosis, consideration of
      neurobiological mechanisms, and routes for intervention. DISCUSSION: The review
      will provide suggestions for future study and research, and a future article will
      describe behavioral and educational strategies psychiatrists may use in
      alleviating cancer fatigue.

PMID- 18621931
TI  - Differences in lymphocyte developmental potential between human embryonic stem
      cell and umbilical cord blood-derived hematopoietic progenitor cells.
AB  - Hematopoietic progenitor cells derived from human embryonic stem cells (hESCs)
      develop into diverse mature hematopoietic lineages, including lymphocytes.
      Whereas functional natural killer (NK) cells can be efficiently generated in
      vitro from hESC-derived CD34(+) cells, studies of T- and B-cell development from
      hESCs have been much more limited. Here, we demonstrate that despite expressing
      functional Notch-1, CD34(+) cells from hESCs did not derive T cells when
      cocultured with OP9 cells expressing Delta-like 1, or in fetal thymus organ
      culture. hESC-derived CD34(+) cells also did not produce B cells in vitro. In
      contrast, CD34(+) cells isolated from UCB routinely generated T and B cells when
      cultured in the same conditions. Notably, both undifferentiated hESCs, and sorted
      hESC-derived populations with hematopoietic developmental potential exhibited
      constitutive expression of ID family genes and of transcriptional targets of stem
      cell factor-induced signaling. These pathways both inhibit T-cell development and
      promote NK-cell development. Together, these results demonstrate fundamental
      differences between hESC-derived hematopoietic progenitors and analogous primary
      human cells. Therefore, hESCs can be more readily supported to differentiate into
      certain cell types than others, findings that have important implications for
      derivation of defined lineage-committed populations from hESCs.

PMID- 18621934
TI  - Successful implementation of an alcohol-withdrawal pathway in a general hospital.
AB  - BACKGROUND: Although alcohol use and abuse are common among general-hospital
      inpatients, many patients are inadequately assessed and treated for alcohol
      withdrawal. OBJECTIVE: The purpose of this study was to determine whether the
      implementation of a clinical pathway for the treatment of alcohol withdrawal in
      medical inpatients would result in improvements in clinical practice and patient
      outcomes. METHOD: Authors retrospectively reviewed 80 patient records (including
      40 of those treated before the implementation of a pathway and 40 of those
      treated after pathway implementation). RESULTS: Assessment procedures and
      ordering patterns of physicians (medical house staff and staff physicians)
      shifted in a fashion consistent with the new treatment guidelines. Patient
      outcomes (e.g., length of stay and the incidence of delirium) improved for those
      patients who received benzodiazepines within the range of the pathway guidelines.
      CONCLUSIONS: Timely assessment and staff education can shift prescription
      patterns, increase patient monitoring, and reduce costs associated with alcohol
      withdrawal.

PMID- 18621935
TI  - Motor symptoms in 100 patients with delirium versus control subjects: comparison
      of subtyping methods.
AB  - BACKGROUND: Different motor presentations of delirium may represent clinically
      meaningful subtypes. OBJECTIVE: Authors sought to evaluate delirium phenomena.
      METHOD: They used three non-validated delirium psychomotor subtype schemas,
      applied to a palliative-care population. Their unique items were merged to
      comprise a 30-item Delirium Motor Checklist (DMC) used to collect data, rate each
      schema, and determine subtype frequencies in 100 consecutive DSM-IV delirium
      patients and 52 medically-matched control subjects without delirium. The Delirium
      Rating Scale-Revised-98 (DRS-R98) assessed delirium severity, and subtype
      categorization using its two motor items was compared with the scale that used
      the psychomotor schema. RESULTS: In delirium, motor disturbance was present in
      100% by DMC versus 92% by DRS-R98 motor items; the DMC motor items also
      significantly distinguished delirium from control subjects. Motor subtype
      classification (hyperactive, hypoactive, mixed, and none) varied among the four
      methods, with low concordance across all four methods and 76% concordance for
      pairwise comparisons. The DRS-R-98 identified the most hypoactive delirium cases.
      CONCLUSION: Motor disturbances are common in delirium, although whether they
      represent clinical subtypes is confounded by methodological issues. New motor
      subtyping methods are needed that are validated in other medical populations, use
      matched control subjects, and have higher sensitivity and specificity for pure
      motor features.

PMID- 18621936
TI  - Pre-existing major depression predicts in-hospital cardiac complications after
      acute myocardial infarction.
AB  - BACKGROUND: Depression (MDD) and anxiety have been associated with negative long
      term outcomes among patients with acute myocardial infarction (MI). OBJECTIVE:
      The objective of the study was to determine whether MDD and anxiety preceding MI
      were associated with in-hospital post-MI cardiac complications. METHOD: Subjects
      (N=129) underwent psychiatric interviews within 72 hours of MI and were evaluated
      for five in-hospital cardiac complications (recurrent ischemia, ventricular
      arrhythmia, ventricular arrhythmia requiring intervention, congestive heart
      failure, and reinfarction). RESULTS: Current (pre-MI) MDD was a significant and
      independent predictor of all complications except recurrent ischemia on
      multivariate regression analysis. In contrast, pre-MI anxiety was not associated
      with complications. CONCLUSION: These findings underscore the importance of
      identifying and treating MDD in post-MI patients and those at risk for MI.

PMID- 18621937
TI  - Alexithymia and childhood abuse among patients attending primary and psychiatric
      care: results of the RADEP Study.
AB  - BACKGROUND: Some authors have suggested that the background of alexithymia is
      related to affective development during early childhood. OBJECTIVE: Authors
      studied the associations between alexithymia and childhood emotional neglect and
      sexual and physical abuse, also taking into account the significance of
      concomitant psychopathology. METHOD: Associations between childhood difficulties
      and adulthood alexithymia were studied with samples of primary-care (N=1,033) and
      mental-health center (N=243) outpatients assessed by The Toronto Alexithymia
      Scale and questionnaires for depressive, manic, and psychotic symptoms, and
      childhood difficulties. RESULTS: No association between alexithymia and childhood
      abuse was found in mental-health center patients. Among primary-care patients,
      alexithymia total score and difficulty in identifying feelings and difficulty in
      describing feelings were associated with childhood emotional, sexual, and
      physical abuse. CONCLUSION: After controlling for psychopathology, there still
      remained an association with difficulty in identifying feelings and most abuse
      and neglect variables. These findings serve to strengthen the theory of
      alexithymia as a developmental process starting in childhood.

PMID- 18621938
TI  - Depression, anxiety, and neuropsychological performance in coronary artery bypass
      graft patients: a follow-up study.
AB  - BACKGROUND: Undergoing coronary-artery bypass surgery (CABG) remains a
      significant life-event, with an important psycho-emotional impact on patients and
      their families. OBJECTIVE: The authors examined the incidence and course of
      depression and anxiety in CABG patients before and after surgery. METHOD: The
      long-term relationship between mood disorders and neuropsychological deficits was
      studied 1 day before and 6 days (N=53), 6 months (N=37), and 3-5 years (N=43)
      after the procedure. RESULTS: Before surgery, one-third of the patients showed
      mild-to-moderate cognitive-affective symptoms of depression. After surgery, one
      fourth still showed elevated depression scores, whereas anxiety was significantly
      decreased at all post-operative time-points. Patients with higher pre-operative
      symptoms of depression showed sustained feelings of depression after surgery.
      Visuomotor performance was most affected by mood. CONCLUSION: Data indicated that
      patients with preoperative moderate cognitive-affective depression could be at
      risk for sustained feelings of depression even up to 5 years after surgery.

PMID- 18621939
TI  - Clusters of alcohol use disorders diagnostic criteria and predictors of alcohol
      use after liver transplantation for alcoholic liver disease.
AB  - BACKGROUND: Establishing the correct alcohol use disorder diagnosis is clinically
      relevant because several reports of post-transplant alcohol use suggest that a
      pre-transplant diagnosis of alcohol dependence (rather than abuse) predicts
      relapse to alcohol use. Numerous combinations of specific symptoms are possible
      to achieve diagnostic significance. OBJECTIVE: The authors hypothesized that
      there would be distinct clusters of liver transplant recipients who showed
      specific combinations of alcohol-related symptoms and that these clusters would
      be predictive of alcohol-abuse outcome after transplant. METHOD: A group of 120
      ALD liver transplant recipients received the Structured Clinical Interview for
      DSM-IV (SCID) module for alcohol abuse/dependence, and a cluster analysis was
      performed. RESULTS: Within the clusters of those with alcohol dependence, cluster
      assignment did not predict those more likely to drink. However, those assigned to
      the alcohol abuse cluster were significantly less likely to drink than those with
      alcohol dependence. CONCLUSION: Results therefore suggest that the prognosis
      regarding continued abstinence posttransplant is much more positive for
      individuals with a diagnosis of abuse than for those who meet criteria for
      alcohol dependence.

PMID- 18621940
TI  - Electroconvulsive therapy in a candidate for heart transplant with an implantable
      cardiovertor defibrillator and cardiac contractility modulator.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) can be life-saving in treating
      depression, even for high-risk cardiac patients. A 56-year-old man with type 2
      diabetes and dilated cardiomyopathy, using both a defibrillator and an
      experimental cardiac contractility modulator, had had episodes of severe
      depression superimposed on dysthymia for 27 years, with a current exacerbation
      over the past 2 years, and little response to antidepressant treatment. METHOD:
      He received a course of 12 ECTs (6 right-unilateral and 6 left-anterior/right
      temporal electrode placements). RESULTS: After these, he was judged moderately
      but not dramatically improved. DISCUSSION: Serious adverse events, such as
      myocardial infarction, lethal arrhythmias, and cardiac rupture are possible in
      these high-risk patients, especially those with ejection fractions <50%, previous
      myocardial infarction, or significant arrhythmias. This case illustrates the
      complex decision-making involved and the need for close interdisciplinary
      collaboration entailed in preparing a high-risk patient with an implanted device
      for ECT.

PMID- 18621941
TI  - Schizophreniform disorder after heat injury in a military recruit.

PMID- 18621942
TI  - A preliminary attempt to personalize risperidone dosing using drug-drug
      interactions and genetics: part II.

PMID- 18621943
TI  - The precipitation of mania by citalopram in a patient with interferon-induced
      depression.

PMID- 18621944
TI  - The future of the DSM pain disorder category.

PMID- 18621945
TI  - Calmodulin7 plays an important role as transcriptional regulator in Arabidopsis
      seedling development.
AB  - Although calmodulin (CaM) is known to play multiple regulatory roles in
      eukaryotes, its direct function as transcriptional regulator is unknown.
      Furthermore, the physiological functions of CaM are largely unknown in plants.
      Here, we show that one of the four Arabidopsis thaliana CaM isoforms, CAM7, is a
      transcriptional regulator that directly interacts with the promoters of light
      inducible genes and promotes photomorphogenesis. CAM7 overexpression causes
      hyperphotomorphogenic growth and an increase in the expression of light-inducible
      genes. Mutations in CAM7 produce no visible effects on photomorphogenic growth,
      indicating likely redundant gene functions. However, cam7 mutants display reduced
      expression of light-inducible genes, and cam7 hy5 double mutants show an
      enhancement of the hy5 phenotype. Moreover, overexpression of CAM7 can partly
      suppress the hy5 phenotype, indicating that the two factors work together to
      control light-induced seedling development. The mutational and transgenic
      studies, together with physiological analyses, illustrate the concerted function
      of CAM7 and HY5 basic leucine zipper transcription factor in Arabidopsis seedling
      development.

PMID- 18621948
TI  - The social and political functioning of states and the homicide of media workers.

PMID- 18621946
TI  - RXLR-mediated entry of Phytophthora sojae effector Avr1b into soybean cells does
      not require pathogen-encoded machinery.
AB  - Effector proteins secreted by oomycete and fungal pathogens have been inferred to
      enter host cells, where they interact with host resistance gene products. Using
      the effector protein Avr1b of Phytophthora sojae, an oomycete pathogen of soybean
      (Glycine max), we show that a pair of sequence motifs, RXLR and dEER, plus
      surrounding sequences, are both necessary and sufficient to deliver the protein
      into plant cells. Particle bombardment experiments demonstrate that these motifs
      function in the absence of the pathogen, indicating that no additional pathogen
      encoded machinery is required for effector protein entry into host cells.
      Furthermore, fusion of the Avr1b RXLR-dEER domain to green fluorescent protein
      (GFP) allows GFP to enter soybean root cells autonomously. The conclusion that
      RXLR and dEER serve to transduce oomycete effectors into host cells indicates
      that the >370 RXLR-dEER-containing proteins encoded in the genome sequence of P.
      sojae are candidate effectors. We further show that the RXLR and dEER motifs can
      be replaced by the closely related erythrocyte targeting signals found in
      effector proteins of Plasmodium, the protozoan that causes malaria in humans.
      Mutational analysis of the RXLR motif shows that the required residues are very
      similar in the motifs of Plasmodium and Phytophthora. Thus, the machinery of the
      hosts (soybean and human) targeted by the effectors may be very ancient.

PMID- 18621949
TI  - Doubts on the appropriateness of universal human papillomavirus vaccination: is
      evidence on public health benefits already available?

PMID- 18621947
TI  - Mutation of the plastidial alpha-glucan phosphorylase gene in rice affects the
      synthesis and structure of starch in the endosperm.
AB  - Plastidial phosphorylase (Pho1) accounts for approximately 96% of the total
      phosphorylase activity in developing rice (Oryza sativa) seeds. From mutant
      stocks induced by N-methyl-N-nitrosourea treatment, we identified plants with
      mutations in the Pho1 gene that are deficient in Pho1. Strikingly, the size of
      mature seeds and the starch content in these mutants showed considerable
      variation, ranging from shrunken to pseudonormal. The loss of Pho1 caused smaller
      starch granules to accumulate and modified the amylopectin structure. Variation
      in the morphological and biochemical phenotype of individual seeds was common to
      all 15 pho1-independent homozygous mutant lines studied, indicating that this
      phenotype was caused solely by the genetic defect. The phenotype of the pho1
      mutation was temperature dependent. While the mutant plants grown at 30 degrees C
      produced mainly plump seeds at maturity, most of the seeds from plants grown at
      20 degrees C were shrunken, with a significant proportion showing severe
      reduction in starch accumulation. These results strongly suggest that Pho1 plays
      a crucial role in starch biosynthesis in rice endosperm at low temperatures and
      that one or more other factors can complement the function of Pho1 at high
      temperatures.

PMID- 18621950
TI  - Integrating research and action: a systematic review of community-based
      participatory research to address health disparities in environmental and
      occupational health in the USA.
AB  - INTRODUCTION: Integrating research and action represents a goal and key
      principles of community-based participatory research (CBPR), but there has been
      little effort to synthesise the literature to evaluate whether such integration
      is occurring. OBJECTIVES: (1) To examine the extent to which CBPR integrates
      action to effect community-level change and (2) to ascertain factors that
      facilitate such integration. METHODS: Original articles reporting on CBPR in
      environmental and occupational health in the USA were identified primarily
      through a MEDLINE search. Inceptions, processes, methods and outcomes of the
      projects were reviewed. RESULTS: In 14 of the 20 studies reviewed, CBPR led to
      community-level action to improve the health and well-being of the community
      members. Observational studies that investigated problems posed by the affected
      community and that incorporated qualitative methods were more likely to lead to
      action. The collaboration among government scientists, university researchers and
      community partners emerged as a new model of CBPR partnerships that effectively
      integrates research and action. CONCLUSIONS: To help CBPR better integrate
      research and action, a shift towards community-initiated and action-oriented
      observational studies might be needed.

PMID- 18621951
TI  - Glossary of terms relating to capture-recapture methods.
AB  - This glossary provides basic definitions for terms that have a specific meaning
      in the application of the capture-recapture methodology, particularly with
      respect to standard techniques for the application of log linear models to
      multiple lists. In epidemiology, capture-recapture is used for prevalence
      estimation. It is intended that, as well as being a central point of reference
      for terms used in the capture-recapture methodology, this glossary should provide
      a resource for those new to this methodology. It aims to provide a simple
      introduction using terms that should be understood by an uninitiated audience.

PMID- 18621952
TI  - Killing the canary: the international epidemiology of the homicide of media
      workers.
AB  - OBJECTIVES: To describe the international epidemiology of the homicide of media
      workers, and investigate country-level risk factors. METHODS: Data on the
      homicides occurring from 2002 to 2006 were collected and collated from five
      international databases. Analyses included consideration of seven existing
      international indices relating to human development, and to the social and
      political functioning of states. RESULTS: During the 5-year period, 370 deaths in
      54 countries met our definitions of homicides and media workers. Almost all (89%)
      were nationals of the country in which they died. The annual number of such
      homicides globally has more than doubled, from 41 in 2002 to 104 in 2006
      (including 49 in Iraq in 2006). Less than 25% of the homicides of media workers
      over the last 5 years have resulted in an arrest or prosecution. Statistically
      significant associations (p<0.001; Political Terror Scores, OR 1.15; Corruption
      Perceptions Index, OR 0.53; Overall Failed State Index, OR 1.05; Failed State
      Index 7, OR 1.52; Failed State Index 9, OR 1.55; Failed State Index 10, OR 1.61)
      were found on logistic regression between the occurrence of the homicide of media
      workers in countries and scoring on six of the seven indices associated with
      country-level sociopolitical development. These indices reflected high levels of
      political terror and corruption, low government legitimisation, poor human
      rights, and uncontrolled armed groups. However, in terms of the homicide rate for
      countries, these associations were significant for only four of the seven indices
      (the general functionality of government, ability of governments to control armed
      groups, the level of political terror, and the level of violation of rights).
      CONCLUSIONS: The homicide of media workers increased substantially in this 5-year
      period and was found to be particularly concentrated in selected countries such
      as Iraq. The authors were able to identify specific sociopolitical risk factors
      for homicide occurrence, and for homicide rates at the country level.

PMID- 18621953
TI  - Environmental attributes related to walking and bicycling at the individual and
      contextual level.
AB  - OBJECTIVE: The aim of the present paper was to give insight into the practical
      consequences of using either single-level or multilevel regression analyses on
      data from research on environmental determinants of physical activity. METHODS:
      For this purpose, results from single-level and multilevel regression analyses on
      comparable attributes of the environment were compared using a combination of
      individual and aggregated data, merged at the neighbourhood level. RESULTS: Using
      only individual level data, applying multilevel instead of single-level analyses
      did not substantially influence the results. However, ignoring the multilevel
      structure of our data by applying single-level in stead of multilevel analyses
      resulted in statistically significant associations for all the environmental
      attributes under study. Moreover, using information on environmental attributes
      at both the individual and the contextual level to adjust associations at one
      level for the other level showed that associated environmental attributes tend to
      be associated either at the individual or at the contextual level. CONCLUSIONS:
      These results stress the importance for reviews and meta-analyses of recording
      type of measurement and type of analytical strategy used and incorporating them
      in the review process. Using advanced multilevel designs will still only partly
      solve the methodological issues involved in studying environmental attributes
      associated with physical activity, but it will help in disentangling this complex
      relationship. Therefore, it is recommended that, whenever there is a presumably
      relevant grouping (context; eg neighbourhoods) in a study, a multilevel approach
      should at least be considered.

PMID- 18621954
TI  - Neighbourhood socioeconomic status, maternal education and adverse birth outcomes
      among mothers living near highways.
AB  - BACKGROUND: Residential proximity to highways is a potential proxy for exposure
      to traffic-related pollution that has been linked to adverse birth outcomes. We
      evaluated whether proximity to highway interacts with individual and
      neighbourhood socioeconomic status (SES) to influence birth outcomes. METHODS:
      The study population consisted of all live singleton births in Montreal, Canada,
      from 1997 to 2001 (n = 99,819). Proximity was defined as residing within 200 m of
      a highway. Neighbourhood SES was measured for census tracts as the proportion of
      families below the low-income threshold. Individual SES was represented by
      maternal education. Using multilevel logistic regression, the odds of preterm
      birth (PTB), low birthweight (LBW) and small-for-gestational-age (SGA) birth were
      calculated for mothers residing in proximity to highways, accounting for
      individual and neighbourhood SES. Effect modification between SES and proximity
      to highway was tested for each outcome. RESULTS: In wealthy neighbourhoods,
      proximity to highway was associated with an elevated odds of PTB (OR 1.58, 95% CI
      1.23 to 2.04), LBW (OR 1.81, 95% CI 1.36 to 2.41) and SGA birth (OR 1.32, 95% CI
      1.05 to 1.66). For highly educated mothers, proximity to highway was associated
      with PTB (OR 1.25, 95% CI 1.07 to 1.46) and LBW (OR 1.24, 95% CI 1.03 to 1.49),
      but the association was borderline for SGA birth (OR 1.15, 95% CI 1.00 to 1.32).
      Proximity to highway was not associated with birth outcomes in other maternal and
      neighbourhood SES categories. CONCLUSION: Counterintuitively, high SES mothers
      may be more likely than low SES mothers to experience adverse births associated
      with residential proximity to highway.

PMID- 18621955
TI  - Individual determinants of primary healthcare utilisation in Gaza Strip,
      Palestine.
AB  - OBJECTIVES: To examine the extent to which primary care patients are using the
      primary healthcare (PHC) services in Gaza Strip, Palestine, and to determine the
      factors that are associated with the use of these services. METHODS: Using
      Andersen's behavioural model, the authors interviewed 956 PHC attendees. Patients
      were questioned about predisposing factors: age, sex, marital status, education,
      work status, household size, life events (psychological and financial), perceived
      living conditions and health locus of control. Enabling factors included
      urbanisation and household income. Need factors included self-rated health.
      Healthy lifestyle was measured by two variables: smoking and physical activity.
      Outcome factors were measured by patients' satisfaction with PHC. RESULTS: The
      study revealed that the majority of interviewed patients (64.7%) reported high
      use (>3 times per 6 months) of PHC within the 6-month period before the
      interview. The main factors found to be associated with high use of PHC were
      older age, married and divorced/widowed status, perceived bad living conditions,
      not working, high level of income, poorly rated health status and current smoking
      habit. CONCLUSIONS: Gazean primary care patients are high users of PHC services.
      The increased use of these services is associated with the basic predisposing,
      enabling and needs factors and with the unique bad living conditions. Tobacco use
      was another aspect associated with high use of PHC. Effective health management,
      based on promoting a healthy lifestyle, is needed. The findings of this study can
      be used to improve health service planning and guide decision-makers towards
      healthcare resource allocation according to healthcare needs.

PMID- 18621956
TI  - Exposure to indoor mould and children's respiratory health in the PATY study.
AB  - BACKGROUND: Living in a damp or mouldy home reportedly damages children's
      respiratory health, yet mould appears not to be a prominent risk factor in the
      public's perception. Analyses of data on over 58,000 children from the Pollution
      and the Young (PATY) study are presented. In this collaboration, researchers from
      12 cross-sectional studies pooled their data to assess the effects of air quality
      on a spectrum of children's respiratory disorders. METHOD: Original studies were
      conducted in Russia, North America and 10 countries in Eastern and Western
      Europe. Pooled analyses were restricted to children aged 6-12 years. Associations
      between visible mould reported in the household and a spectrum of eight
      respiratory and allergic symptoms were estimated within each study. Logistic
      regressions were used, controlling for individual risk factors and for study
      area. Heterogeneity between study-specific results and mean effects (allowing for
      heterogeneity) were estimated using meta-analysis. RESULTS: Visible mould was
      reported by 13.9% of respondents in Russia, increasing to 39.1% in North America.
      Positive associations between exposure to mould and children's respiratory health
      were seen with considerable consistency across studies and across outcomes.
      Confounder-adjusted combined ORs ranged from 1.30 (95% CI 1.22 to 1.39) for
      "nocturnal cough" to 1.50 (1.31 to 1.73) for "morning cough". Evidence of
      stronger effects in more crowded households was statistically significant for
      only asthma and sensitivity to inhaled allergens. No consistent interactions
      between mould and age, sex or parental smoking were found. CONCLUSION: Indoor
      mould exposure was consistently associated with adverse respiratory health
      outcomes in children living in these diverse countries.

PMID- 18621957
TI  - Tuberculosis associated with household crowding in a developed country.
AB  - BACKGROUND: Tuberculosis (TB) remains an important infectious disease in New
      Zealand (NZ) and globally, but risk factors for transmission are still poorly
      understood. This research aimed to identify whether household crowding
      contributes to TB transmission in NZ. METHODS: This ecological study used TB
      surveillance and census data to calculate TB incidence rates by census area unit
      (CAU). Census data were used to determine CAU characteristics including
      proportion of household crowding (a bedroom deficit of one or more), proportion
      of population who are migrants born in high-TB-incidence countries, median
      household income, and deprivation level. A negative binomial regression model was
      used to estimate the association between TB incidence and household crowding.
      RESULTS: The analysis included 1898 notified TB cases for the 2000-4 period.
      Univariate analysis showed TB incidence at the CAU level was associated with
      household crowding, for the total population and for all ethnic and age groups.
      After adjusting for the covariates of household income, existing TB burden, and
      proportion of migrants from high-TB-incidence countries, multivariate analysis
      showed statistically significant associations between TB incidence and household
      crowding. The incidence rate ratio (IRR) was 1.05 (95% CI 1.02 to 1.08) in the
      total population and 1.08 (95% CI 1.04 to 1.12) for NZ-born people <40 years.
      CONCLUSION: At the CAU level, TB incidence in NZ is associated with household
      crowding. An individual-based study (e.g. case-control) in recently infected
      cases (detected by molecular epidemiology techniques) is suggested to complement
      these findings. Reducing or eliminating household crowding could decrease TB
      incidence in NZ and globally.

PMID- 18621958
TI  - Association between offspring intelligence and parental mortality: a population
      based cohort study of one million Swedish men and their parents.
AB  - BACKGROUND: An inverse association of IQ with mortality has been observed in
      previous studies. Analyses of associations between offspring's IQ and parental
      mortality in biological and non-biological family relations may shed light on
      genetic and environmental influences. METHODS: In a target cohort of 1,235,375
      Swedish men, 931,825 (75%) men had complete data on all variables used. IQ of
      offspring was measured at age 18 and mothers and father were followed, on
      average, for 21.2 years and 19.7 years, respectively, with respect to all-cause
      and cause-specific mortality (cardiovascular disease, coronary heart disease,
      stroke and diabetes). The analyses were conducted by proportional hazards
      regression with adjustment for parental occupation, education and income.
      RESULTS: In adjusted analyses using IQ as a continuous variable over a standard
      nine-point scale, hazards ratio (HR) for all-cause mortality was 0.96 (95% CI
      0.96 to 0.96) for fathers and 0.95 (0.95 to 0.95) for mothers. The corresponding
      HRs were 0.99 (0.97 to 1.00) for step-fathers and 0.97 (0.95 to 0.99) for step
      mothers. In adjusted analyses, HRs for CVD mortality among fathers and mothers
      were 0.97 (0.96 to 0.97) and 0.94 (0.93 to 0.94) respectively. The corresponding
      HRs for diabetes mortality were 0.91 (0.89 to 0.92) among fathers and 0.85 (0.83
      to 0.87) among mothers. CONCLUSIONS: The associations found in non-biological
      family relationships suggest shared environmental influences and/or assortative
      mating. Stronger IQ-mortality associations in biological than non-biological
      relationships suggest genetic influences. Stronger inverse offspring IQ-parental
      mortality associations in mothers than in fathers might be due to environmental
      factors or epigenetic mechanisms.

PMID- 18621959
TI  - Do consequences of a given pattern of drinking vary by socioeconomic status? A
      mortality and hospitalisation follow-up for alcohol-related causes of the Finnish
      Drinking Habits Surveys.
AB  - BACKGROUND: Socioeconomic differences in alcohol-related mortality and
      hospitalisations, as based on register data, are larger than socioeconomic
      differences in various types of harmful drinking, as based on survey data.
      OBJECTIVE: The aim was to use a follow-up study to examine whether differential
      drinking patterns between socioeconomic groups explain the observed differences
      in alcohol-related mortality and hospitalisations, or whether similar drinking
      patterns predict higher mortality among lower socioeconomic groups. METHOD: The
      study population included Finns who participated in cross-sectional surveys on
      drinking habits in 1969, 1976 or 1984 when aged 25-69 (n = 6406). They were
      followed up for alcohol-related mortality and hospitalisations (n = 180) for 16
      years. Drinking patterns were measured by total consumption, frequency of
      subjective intoxication and of drinking different amounts of alcohol at a time,
      and by volume of consumption that was drunk in heavy drinking occasions and non
      heavy drinking occasions. RESULTS: Compared with non-manual workers, manual
      workers had a 2.06-fold hazard of alcohol-related death or hospitalisation.
      Adjustment for drinking patterns explained only a small fraction of the excess
      hazard among manual workers. Additionally, in each category of total consumption
      and in each level of the volume drunk in heavy drinking occasions, the risk of
      alcohol-related death and hospitalisation was higher for manual than for non
      manual workers. CONCLUSIONS: Consequences of similar drinking patterns are more
      severe for those with lower socioeconomic status. Future studies are needed to
      explain how higher socioeconomic groups manage to escape the consequences of
      drinking that others have to face.

PMID- 18621960
TI  - Dietary patterns related to attainment in school: the importance of early eating
      patterns.
AB  - OBJECTIVES: To empirically test the impact of dietary intake at several time
      points in childhood on children's school attainment and to investigate whether
      any differences in school attainment between children who ate packed lunches or
      school meals was due to who these children were, their pre-school dietary
      patterns, or to what they ate at school. DESIGN: Using longitudinal data
      available in the Avon Longitudinal Study of Parents and Children (ALSPAC),
      multivariate linear regression was used to assess the relative importance of diet
      at different ages for school attainment. MAIN OUTCOME MEASURES: Three indicators
      of school attainment were used: at ages 4-5 entry assessments to school, at ages
      6-7 Key Stage 1 national tests and at ages 10-11 Key Stage 2 national tests.
      These outcome variables were measured in levels as well as in changes from the
      previous educational stage. RESULTS: The key finding at age 3 was that "junk
      food" dietary pattern had a negative association with the level of school
      attainment. A weak association remained after controlling for the impact of other
      dietary patterns at age 3, dietary patterns at ages 4 and 7 and other confounding
      factors. The authors did not find evidence that eating packed lunches or eating
      school meals affected children's attainment, once the impact of junk food dietary
      pattern at age 3 was accounted for in the model. CONCLUSIONS: Early eating
      patterns have implications for attainment that appear to persist over time,
      regardless of subsequent changes in diet.

PMID- 18621961
TI  - History in health and health services: exploring the possibilities.
AB  - Historical skills--especially the methodologies involved in interpreting a wide
      range of sources--can provide a useful analysis of the structure and function of
      health services, and be used as a means of improving public understanding of the
      expectations and experiences of health and health care. This paper discusses some
      key examples of different strategies used by historians to show how they can
      collaborate effectively with health professionals.

PMID- 18621962
TI  - Poverty and infant mortality in the Eastern Mediterranean region: a meta
      analysis.
AB  - OBJECTIVES: To test the hypothesis that poverty is associated with infant
      mortality in Eastern Mediterranean countries and to measure the strength of the
      association. METHODS: A bibliographic search was conducted. The studies including
      data regarding deaths during the first year of life, socioeconomic status of the
      household and/or maternal literacy were selected. Nine studies, conducted in the
      Eastern Mediterranean region, fulfilled the inclusion criteria. These included
      seven cross-sectional surveys and two case-control studies. Maternal illiteracy
      and low socioeconomic status were used to show the level of poverty in each
      household. Risk estimates for low socioeconomic status and maternal illiteracy
      were extracted from each study. Meta-analysis was performed for the association
      between exposure groups of low socioeconomic status and maternal illiteracy and
      the outcome of death within the first year of life. MAIN RESULTS: Poverty was
      associated with an increased risk of infant death (pooled OR 1.52, 95% CI 1.38 to
      1.67), significant at p<0.0001. There was a significantly increased risk of
      infant death among illiterate mothers (OR 1.72, 95% CI 1.42 to 2.08) compared
      with literate mothers. The meta-analysis OR for an association between low
      socioeconomic status subgroup and infant death was 1.37 (95% CI 1.25 to 1.49),
      significant at p<0.0001. CONCLUSIONS: This meta-analysis indicates that there is
      a significantly increased mortality risk in infants born in poor households. The
      results suggest that policies aimed at poverty alleviation and female literacy
      will substantially contribute to a decrease in infant mortality.

PMID- 18621963
TI  - When can group level clustering be ignored? Multilevel models versus single-level
      models with sparse data.
AB  - OBJECTIVE: The use of multilevel modelling with data from population-based
      surveys is often limited by the small number of cases per level-2 unit, prompting
      many researchers to use single-level techniques such as ordinary least squares
      regression. DESIGN: Monte Carlo simulations are used to investigate the effects
      of data sparseness on the validity of parameter estimates in two-level versus
      single-level models. SETTING: Both linear and non-linear hierarchical models are
      simulated in order to examine potential differences in the effects of small group
      size across continuous and discrete outcomes. Results are then compared with
      those obtained using disaggregated techniques (ordinary least squares and
      logistic regression). MAIN RESULTS: At the extremes of data sparseness (two
      observations per group), the group level variance components are overestimated in
      the two-level models. But with an average of only five observations per group,
      valid and reliable estimates of all parameters can be obtained when using a two
      level model with either a continuous or a discrete outcome. In contrast,
      researchers run the risk of Type I error (standard errors biased downwards) when
      using single-level models even when there are as few as two observations per
      group on average. Bias is magnified when modelling discrete outcomes.
      CONCLUSIONS: Multilevel models can be reliably estimated with an average of only
      five observations per group. Disaggregated techniques carry an increased risk of
      Type I error, even in situations where there is only limited clustering in the
      data.

PMID- 18621964
TI  - Effect of voting abstention and life course socioeconomic position on self
      reported health.

PMID- 18621965
TI  - A new approach to the quantification of degree of reciprocity in distylous (sensu
      lato) plant populations.
AB  - BACKGROUND AND AIMS: Although evolution of sexual polymorphism has been
      traditionally analysed using discrete characters, most of these polymorphisms are
      continuous. This is the case of heterostyly. Heterostyly is a floral polymorphism
      successfully used as a model to study the evolution of the sexual systems in
      plants. It involves the reciprocal positioning of anthers and stigmas in flowers
      of different plants within the same population. Studies of the functioning of
      heterostyly require the quantification of the degree of reciprocity between
      morphs of heterostylous species. Some reciprocity indices have been proposed
      previously, but they show significant limitations that need to be dealt with.
      This paper analyses these existing indices, and proposes a new index that aims to
      avoid their main problems (e.g. takes into account population variability and
      offers a single value per population). METHODS: The new index is based on the
      comparison of the position of every single sexual organ in the population with
      each and every organ of the opposite sex. To carry out all the calculations, a
      macro was programmed with MS Visual Basic in MS Excel. The behaviour of the index
      is tested using hypothetical data to simulate different situations of dimorphic
      populations; the index is also tested with some actual populations of different
      species of the genus Lithodora. RESULTS AND CONCLUSIONS: The index of reciprocity
      proposed here is a sound alternative to previous indices: it compares stigma
      stamen height gaps for all potential crosses in the population, it comprises
      stigma-stamen distance as well as dispersion, it is not skewed by the more
      frequent sex, and it can be meaningfully compared between populations and
      species. It has produced solid results for both hypothetical and natural
      populations.

PMID- 18621966
TI  - Adaptation of rhizome connections in drylands: increasing tolerance of clones to
      wind erosion.
AB  - BACKGROUND AND AIMS: Wind erosion is a severe stress for plants in drylands, but
      the mechanisms by which plants withstand erosion remain largely unknown. Here,
      the hypothesis is tested that maintaining rhizome connections helps plants to
      tolerate erosion. METHODS: Five transects were established across an inland dune
      in Inner Mongolia, China, and measurements were made of leaf number, biomass per
      ramet and rhizome depth of Psammochloa villosa in 45 plots. In 40 x 40 cm plots
      of P. villosa on another dune, the top 15 or 30 cm of sand was removed for 1.5 or
      3 months to simulate short- and long-term moderate and severe erosion,
      respectively, with untreated plots as controls, and the rhizomes at the edges of
      half of the plots were severed to mimic loss of rhizome connections. KEY RESULTS:
      Leaf number and biomass per ramet showed quadric relationships with rhizome
      depth; when rhizomes were exposed to the air, the associated ramets either died
      or became very weak. Ramet number, leaf number and biomass per plot decreased
      with increasing erosion severity. Rhizome connections did not affect these traits
      under control or short-term erosion, but increased them under long-term erosion.
      CONCLUSIONS: Rhizome connections alleviated the negative effects of erosion on P.
      villosa, very likely because the erosion-stressed ramets received water and/or
      photosynthates translocated from those connected ramets that were not subject to
      erosion. This study provides the first evidence that maintaining rhizome
      connections helps plants to tolerate erosion in drylands.

PMID- 18621968
TI  - Standardisation in clinical laboratory medicine: an ethical reflection.

PMID- 18621967
TI  - Detailed analysis of the expression of an alpha-gliadin promoter and the
      deposition of alpha-gliadin protein during wheat grain development.
AB  - BACKGROUND AND AIMS: Alpha-gliadin proteins are important for the industrial
      quality of bread wheat flour, but they also contain many epitopes that can
      trigger celiac (coeliac) disease (CD). The B-genome-encoded alpha-gliadin genes,
      however, contain very few epitopes. Controlling alpha-gliadin gene expression in
      wheat requires knowledge on the processes of expression and deposition of alpha
      gliadin protein during wheat grain development. METHODS: A 592-bp fragment of the
      promotor of a B-genome-encoded alpha-gliadin gene driving the expression of a GUS
      reporter gene was transformed into wheat. A large number of transgenic lines were
      used for data collection. GUS staining was used to determine GUS expression
      during wheat kernel development, and immunogold labelling and tissue printing
      followed by staining with an alpha-gliadin-specific antibody was used to detect
      alpha-gliadin protein deposited in developing wheat kernels. The promoter
      sequence was screened for regulatory motifs and compared to other available alpha
      gliadin promoter sequences. KEY RESULTS: GUS expression was detected primarily in
      the cells of the starchy endosperm, notably in the subaleurone layer but also in
      the aleurone layer. The alpha-gliadin promoter was active from 11 days after
      anthesis (DAA) until maturity, with an expression similar to that of a 326-bp low
      molecular weight (LMW) subunit gene promoter reported previously. An alpha
      gliadin-specific antibody detected alpha-gliadin protein in protein bodies in the
      starchy endosperm and in the subaleurone layer but, in contrast to the promoter
      activity, no alpha-gliadin was detected in the aleurone cell layer. Sequence
      comparison showed differences in regulatory elements between the promoters of
      alpha-gliadin genes originating from different genomes (A and B) of bread wheat
      both in the region used here and upstream. CONCLUSIONS: The results suggest that
      additional regulator elements upstream of the promoter region used may
      specifically repress expression in the aleurone cell layer. Observed differences
      in expression regulator motifs between the alpha-gliadin genes on the different
      genomes (A and B) of bread wheat leads to a better understanding how alpha
      gliadin expression can be controlled.

PMID- 18621969
TI  - Multiple sclerosis and systemic sclerosis: efficacy of interferon beta on skin
      lesions.

PMID- 18621970
TI  - Pharmacogenetic study of 5,10-methylenetetrahydrofolate reductase C677T and
      thymidylate synthase 3R/2R gene polymorphisms and methotrexate-related toxicity
      in Chinese Han patients with inflammatory arthritis.

PMID- 18621971
TI  - Pretreatment serum levels of anti-cyclic citrullinated peptide antibodies are
      associated with the response to methotrexate in recent-onset arthritis.

PMID- 18621972
TI  - Is there any role for tumour necrosis factor related apoptosis inducing ligand
      osteoprotegerin (TRAIL-OPG) interaction in rheumatoid arthritis?

PMID- 18621973
TI  - Investigating the role of CD24 gene polymorphisms in rheumatoid arthritis.

PMID- 18621974
TI  - Ultrasound-guided intra-articular injections in the wrist in patients with
      rheumatoid arthritis: a double-blind, randomised controlled study.

PMID- 18621975
TI  - The coenzyme a biosynthetic enzyme phosphopantetheine adenylyltransferase plays a
      crucial role in plant growth, salt/osmotic stress resistance, and seed lipid
      storage.
AB  - Coenzyme A (CoA) is an essential cofactor in the metabolism of both prokaryotic
      and eukaryotic organisms and a universal five-step pathway is utilized to
      synthesize CoA from pantothenate. Null mutations in two of the five steps of this
      pathway led to embryo lethality and therefore viable reduction-of-function
      mutations are required to further study its role in plant biology. In this
      article, we have characterized a viable Arabidopsis (Arabidopsis thaliana) T-DNA
      mutant affected in the penultimate step of the CoA biosynthesis pathway, which is
      catalyzed by the enzyme phosphopantetheine adenylyltransferase (PPAT). This ppat
      1 knockdown mutation showed an approximately 90% reduction in PPAT transcript
      levels and was severely impaired in plant growth and seed production. The sum of
      CoA and acetyl-CoA levels was severely reduced (60%-80%) in ppat-1 seedlings
      compared to wild type, and catabolism of storage lipids during seedling
      establishment was delayed. Conversely, PPAT overexpressing lines showed, on
      average, approximately 1.6-fold higher levels of CoA + acetyl-CoA levels, as well
      as enhanced vegetative and reproductive growth and salt/osmotic stress
      resistance. Interestingly, dry seeds of overexpressing lines contained between
      35% to 50% more fatty acids than wild type, which suggests that CoA biosynthesis
      plays a crucial role in storage oil accumulation. Finally, biochemical analysis
      of the recombinant PPAT enzyme revealed an inhibitory effect of CoA on PPAT
      activity. Taken together, these results suggest that the reaction catalyzed by
      PPAT is a regulatory step in the CoA biosynthetic pathway that plays a key role
      for plant growth, stress resistance, and seed lipid storage.

PMID- 18621976
TI  - Geminivirus-mediated gene silencing from Cotton leaf crumple virus is enhanced by
      low temperature in cotton.
AB  - A silencing vector for cotton (Gossypium hirsutum) was developed from the
      geminivirus Cotton leaf crumple virus (CLCrV). The CLCrV coat protein gene was
      replaced by up to 500 bp of DNA homologous to one of two endogenous genes, the
      magnesium chelatase subunit I gene (ChlI) or the phytoene desaturase gene (PDS).
      Cotyledons of cotton cultivar 'Deltapine 5415' bombarded with the modified viral
      vectors manifested chlorosis due to silencing of either ChlI or PDS in
      approximately 70% of inoculated plants after 2 to 3 weeks. Use of the green
      fluorescence protein gene showed that replication of viral DNA was restricted to
      vascular tissue and that the viral vector could transmit to leaves, roots, and
      the ovule integument from which fibers originate. Temperature had profound
      effects on vector DNA accumulation and the spread of endogenous gene silencing.
      Consistent with reports that silencing against viruses increases at higher
      temperatures, plants grown at a 30 degrees C/26 degrees C day/night cycle had a
      greater than 10-fold reduction in viral DNA accumulation compared to plants grown
      at 22 degrees C/18 degrees C. However, endogenous gene silencing decreased at 30
      degrees C/26 degrees C. There was an approximately 7 d delay in the onset of gene
      silencing at 22 degrees C/18 degrees C, but silencing was extensive and persisted
      throughout the life of the plant. The extent of silencing in new growth could be
      increased or decreased by changing temperature regimes at various times following
      the onset of silencing. Our experiments establish the use of the CLCrV silencing
      vector to study gene function in cotton and show that temperature can have a
      major impact on the extent of geminivirus-induced gene silencing.

PMID- 18621977
TI  - Interactions of two transcriptional repressors and two transcriptional activators
      in modulating gibberellin signaling in aleurone cells.
AB  - Gibberellins (GAs) regulate many aspects of plant development, such as
      germination, growth, and flowering. The barley (Hordeum vulgare) Amy32b alpha
      amylase promoter contains at least five cis-acting elements that govern its GA
      induced expression. Our previous studies indicate that a barley WRKY gene,
      HvWRKY38, and its rice (Oryza sativa) ortholog, OsWRKY71, block GA-induced
      expression of Amy32b-GUS. In this work, we investigated the functional and
      physical interactions of HvWRKY38 with another repressor and two activators in
      barley. HvWRKY38 blocks the inductive activities of SAD (a DOF protein) and
      HvGAMYB (a R2R3 MYB protein) when either of these proteins is present
      individually. However, SAD and HvGAMYB together overcome the inhibitory effect of
      HvWRKY38. Yet, the combination of HvWRKY38 and BPBF (another DOF protein) almost
      diminishes the synergistic effect of SAD and HvGAMYB transcriptional activators.
      Electrophoretic mobility shift assays indicate that HvWRKY38 blocks the GA
      induced expression of Amy32b by interfering with the binding of HvGAMYB to the
      cis-acting elements in the alpha-amylase promoter. The physical interaction of
      HvWRKY38 and BPBF repressors is demonstrated via bimolecular fluorescence
      complementation assays. These data suggest that the expression of Amy32b is
      modulated by protein complexes that contain either activators (e.g. HvGAMYB and
      SAD) or repressors (e.g. HvWRKY38 and BPBF). The relative amounts of the
      repressor or activator complexes binding to the Amy32b promoter regulate its
      expression level in barley aleurone cells.

PMID- 18621978
TI  - Identification of the wax ester synthase/acyl-coenzyme A: diacylglycerol
      acyltransferase WSD1 required for stem wax ester biosynthesis in Arabidopsis.
AB  - Wax esters are neutral lipids composed of aliphatic alcohols and acids, with both
      moieties usually long-chain (C(16) and C(18)) or very-long-chain (C(20) and
      longer) carbon structures. They have diverse biological functions in bacteria,
      insects, mammals, and terrestrial plants and are also important substrates for a
      variety of industrial applications. In plants, wax esters are mostly found in the
      cuticles coating the primary shoot surfaces, but they also accumulate to high
      concentrations in the seed oils of a few plant species, including jojoba
      (Simmondsia chinensis), a desert shrub that is the major commercial source of
      these compounds. Here, we report the identification and characterization of WSD1,
      a member of the bifunctional wax ester synthase/diacylglycerol acyltransferase
      gene family, which plays a key role in wax ester synthesis in Arabidopsis
      (Arabidopsis thaliana) stems, as first evidenced by severely reduced wax ester
      levels of in the stem wax of wsd1 mutants. In vitro assays using protein extracts
      from Escherichia coli expressing WSD1 showed that this enzyme has a high level of
      wax synthase activity and approximately 10-fold lower level of diacylglycerol
      acyltransferase activity. Expression of the WSD1 gene in Saccharomyces cerevisiae
      resulted in the accumulation of wax esters, but not triacylglycerol, indicating
      that WSD1 predominantly functions as a wax synthase. Analyses of WSD1 expression
      revealed that this gene is transcribed in flowers, top parts of stems, and
      leaves. Fully functional yellow fluorescent protein-tagged WSD1 protein was
      localized to the endoplasmic reticulum, demonstrating that biosynthesis of wax
      esters, the final products of the alcohol-forming pathway, occurs in this
      subcellular compartment.

PMID- 18621979
TI  - Overexpression of the Arabidopsis 10-kilodalton acyl-coenzyme A-binding protein
      ACBP6 enhances freezing tolerance.
AB  - Small 10-kD acyl-coenzyme A-binding proteins (ACBPs) are highly conserved
      proteins that are prevalent in eukaryotes. In Arabidopsis (Arabidopsis thaliana),
      other than the 10-kD ACBP homolog (designated Arabidopsis ACBP6), there are five
      larger forms of ACBPs ranging from 37.5 to 73.1 kD. In this study, the cytosolic
      subcellular localization of Arabidopsis ACBP6 was confirmed by analyses of
      transgenic Arabidopsis expressing autofluorescence-tagged ACBP6 and western-blot
      analysis of subcellular fractions using ACBP6-specific antibodies. The expression
      of Arabidopsis ACBP6 was noticeably induced at 48 h after 4 degrees C treatment
      by northern-blot analysis and western-blot analysis. Furthermore, an acbp6 T-DNA
      insertional mutant that lacked ACBP6 mRNA and protein displayed increased
      sensitivity to freezing temperature (-8 degrees C), while ACBP6-overexpressing
      transgenic Arabidopsis plants were conferred enhanced freezing tolerance.
      Northern-blot analysis indicated that ACBP6-associated freezing tolerance was not
      dependent on the induction of cold-regulated COLD-RESPONSIVE gene expression.
      Instead, ACBP6 overexpressors showed increased expression of mRNA encoding
      phospholipase Ddelta. Lipid profiling analyses of rosettes from cold-acclimated,
      freezing-treated (-8 degrees C) transgenic Arabidopsis plants overexpressing
      ACBP6 showed a decline in phosphatidylcholine (-36% and -46%) and an elevation of
      phosphatidic acid (73% and 67%) in comparison with wild-type plants. From our
      comparison, the gain in freezing tolerance in ACBP6 overexpressors that was
      accompanied by decreases in phosphatidylcholine and an accumulation of
      phosphatidic acid is consistent with previous findings on phospholipase Ddelta
      overexpressing transgenic Arabidopsis. In vitro filter-binding assays indicating
      that histidine-tagged ACBP6 binds phosphatidylcholine, but not phosphatidic acid
      or lysophosphatidylcholine, further imply a role for ACBP6 in phospholipid
      metabolism in Arabidopsis, including the possibility of ACBP6 in the cytosolic
      trafficking of phosphatidylcholine.

PMID- 18621980
TI  - Molecular and functional analyses support a role of Ornithine-{delta}
      aminotransferase in the provision of glutamate for glutamine biosynthesis during
      pine germination.
AB  - We report the molecular characterization and functional analysis of a gene
      (PsdeltaOAT) from Scots pine (Pinus sylvestris) encoding Orn-delta
      aminotransferase (delta-OAT; EC 2.6.1.13), an enzyme of arginine metabolism. The
      deduced amino acid sequence contains a putative N-terminal signal peptide for
      mitochondrial targeting. The polypeptide is similar to other delta-OATs from
      plants, yeast, and mammals and encoded by a single-copy gene in pine. PsdeltaOAT
      encodes a functional delta-OAT as determined by expression of the recombinant
      protein in Escherichia coli and analysis of the active enzyme. The expression of
      PsdeltaOAT was undetectable in the embryo, but highly induced at early stages of
      germination and seedling development in all different organs. Transcript levels
      decreased in later developmental stages, although an increase was observed in
      lignified stems of 90-d-old plants. An increase of delta-OAT activity was
      observed in germinating embryos and seedlings and appears to mirror the observed
      alterations in PsdeltaOAT transcript levels. Similar expression patterns were
      also observed for genes encoding arginase and isocitrate dehydrogenase.
      Transcripts of PsdeltaOAT and the arginase gene were found widely distributed in
      different cell types of pine organs. Consistent with these results a metabolic
      pathway is proposed for the nitrogen flow from the megagametophyte to the
      developing seedling, which is also supported by the relative abundance of free
      amino acids in embryos and seedlings. Taken together, our data support that delta
      OAT plays an important role in this process providing glutamate for glutamine
      biosynthesis during early pine growth.

PMID- 18621981
TI  - The Omp85-related chloroplast outer envelope protein OEP80 is essential for
      viability in Arabidopsis.
AB  - beta-Barrel proteins of the Omp85 (Outer membrane protein, 85 kD) superfamily
      exist in the outer membranes of Gram-negative bacteria, mitochondria, and
      chloroplasts. Prominent Omp85 proteins in bacteria and mitochondria mediate
      biogenesis of other beta-barrel proteins and are indispensable for viability. In
      Arabidopsis (Arabidopsis thaliana) chloroplasts, there are two distinct types of
      Omp85-related protein: Toc75 (Translocon at the outer envelope membrane of
      chloroplasts, 75 kD) and OEP80 (Outer Envelope Protein, 80 kD). Toc75 functions
      as a preprotein translocation channel during chloroplast import, but the role of
      OEP80 remains elusive. We characterized three T-DNA mutants of the Arabidopsis
      OEP80 (AtOEP80) gene. Selectable markers associated with the oep80-1 and oep80-2
      insertions segregated abnormally, suggesting embryo lethality of the homozygous
      genotypes. Indeed, no homozygotes were identified among >100 individuals, and
      heterozygotes of both mutants produced approximately 25% aborted seeds upon self
      pollination. Embryo arrest occurred at a relatively late stage (globular embryo
      proper) as revealed by analysis using Nomarski optics microscopy. This is
      substantially later than arrest caused by loss of the principal Toc75 isoform,
      atToc75-III (two-cell stage), suggesting a more specialized role for AtOEP80.
      Surprisingly, the oep80-3 T-DNA (located in exon 1 between the first and second
      ATG codons of the open reading frame) did not cause any detectable developmental
      defects or affect the size of the AtOEP80 protein in chloroplasts. This indicates
      that the N-terminal region of AtOEP80 is not essential for the targeting,
      biogenesis, or functionality of the protein, in contrast with atToc75-III, which
      requires a bipartite targeting sequence.

PMID- 18621982
TI  - A novel RNA-binding protein associated with cell plate formation.
AB  - Building a cell plate during cytokinesis in plant cells requires the
      participation of a number of proteins in a multistep process. We previously
      identified phragmoplastin as a cell plate-specific protein involved in creating a
      tubulovesicular network at the cell plate. We report here the identification and
      characterization of a phragmoplastin-interacting protein, PHIP1, in Arabidopsis
      (Arabidopsis thaliana). It contains multiple functional motifs, including a
      lysine-rich domain, two RNA recognition motifs, and three CCHC-type zinc fingers.
      Polypeptides with similar motif structures were found only in plant protein
      databases, but not in the sequenced prokaryotic, fungal, and animal genomes,
      suggesting that PHIP1 represents a plant-specific RNA-binding protein. In
      addition to phragmoplastin, two Arabidopsis small GTP-binding proteins, Rop1 and
      Ran2, are also found to interact with PHIP1. The zinc fingers of PHIP1 were not
      required for its interaction with Rop1 and phragmoplastin, but they may
      participate in its binding with the Ran2 mRNA. Immunofluorescence, in situ RNA
      hybridization, and green fluorescent protein tagging experiments showed the
      association of PHIP1 with the forming cell plate during cytokinesis. Taken
      together, our data suggest that PHIP1 is a novel RNA-binding protein and may play
      a unique role in the polarized mRNA transport to the vicinity of the cell plate.

PMID- 18621983
TI  - Combination of novel green fluorescent protein mutant TSapphire and DsRed variant
      mOrange to set up a versatile in planta FRET-FLIM assay.
AB  - Forster resonance energy transfer (FRET) measurements based on fluorescence
      lifetime imaging microscopy (FLIM) are increasingly being used to assess
      molecular conformations and associations in living systems. Reduction in the
      excited-state lifetime of the donor fluorophore in the presence of an
      appropriately positioned acceptor is taken as strong evidence of FRET.
      Traditionally, cyan fluorescent protein has been widely used as a donor
      fluorophore in FRET experiments. However, given its photolabile nature, low
      quantum yield, and multiexponential lifetime, cyan fluorescent protein is far
      from an ideal donor in FRET imaging. Here, we report the application and use of
      the TSapphire mutant of green fluorescent protein as an efficient donor to
      mOrange in FLIM-based FRET imaging in intact plant cells. Using time-correlated
      single photon counting-FLIM, we show that TSapphire expressed in living plant
      cells decays with lifetime of 2.93 +/- 0.09 ns. Chimerically linked TSapphire and
      mOrange (with 16-amino acid linker in between) exhibit substantial energy
      transfer based on the reduction in the lifetime of TSapphire in the presence of
      the acceptor mOrange. Experiments performed with various genetically and/or
      biochemically known interacting plant proteins demonstrate the versatility of the
      FRET-FLIM system presented here in different subcellular compartments tested
      (cytosol, nucleus, and at plasma membrane). The better spectral overlap with red
      monomers, higher photostability, and monoexponential lifetime of TSapphire makes
      it an ideal FRET-FLIM donor to study protein-protein interactions in diverse
      eukaryotic systems overcoming, in particular, many technical challenges
      encountered (like autofluorescence of cell walls and fluorescence of pigments
      associated with photosynthetic apparatus) while studying plant protein dynamics
      and interactions.

PMID- 18621984
TI  - Dysregulation of elastin expression by fibroblasts in pulmonary emphysema: role
      of cellular retinoic acid binding protein 2.
AB  - BACKGROUND: All-trans retinoic acid (ATRA) stimulates elastin synthesis by lung
      fibroblasts and induces alveolar regeneration in animal models of pulmonary
      emphysema. However, ATRA treatment has had disappointing results in human
      emphysema. It was hypothesised that a defect in the ATRA signalling pathway
      contributes to the defect of alveolar repair in the human emphysematous lung.
      METHODS: Fibroblasts were cultured from the lung of 10 control subjects and eight
      patients with emphysema. Elastin and retinoic acid receptor (RAR)-beta mRNAs were
      measured in those cells in the presence of incremental concentrations of ATRA.
      RARs, retinoic X receptors (RXRs) and cellular retinoic acid binding protein
      (CRABP) 1 and 2 mRNAs were measured as well as CRABP2 protein content. The effect
      of CRABP2 silencing on elastin and RAR-beta expression in response to ATRA was
      measured in MRC5 lung fibroblasts. RESULTS: ATRA at 10(-9) M and 10(-8) M
      increased median elastin mRNA expression by 182% and 126% in control but not in
      emphysema fibroblasts. RAR-beta mRNA expression was induced by ATRA in control as
      well as emphysema fibroblasts. RARs, RXRs and CRABP1 mRNAs were similarly
      expressed in control and emphysema fibroblasts while CRABP2 mRNA and protein were
      lower in emphysema fibroblasts. CRABP2 silencing abrogated the induction of
      elastin but not RAR-beta expression by ATRA in MRC5 fibroblasts. CONCLUSION:
      Pulmonary emphysema fibroblasts fail to express elastin under ATRA stimulation.
      CRABP2, which is necessary for elastin induction by ATRA in MRC-5 cells, is
      expressed at low levels in emphysema fibroblasts. This alteration in the retinoic
      acid signalling pathway in lung fibroblasts may contribute to the defect of
      alveolar repair in human pulmonary emphysema. These results are the first
      demonstration of the involvement of CRABP2 in elastin expression.

PMID- 18621985
TI  - Cost effectiveness of therapy with combinations of long acting bronchodilators
      and inhaled steroids for treatment of COPD.
AB  - BACKGROUND: Little is known about the combination of different medications in
      chronic obstructive pulmonary disease (COPD). This study determined the cost
      effectiveness of adding salmeterol (S) or fluticasone/salmeterol (FS) to
      tiotropium (T) for COPD. METHODS: This concurrent, prospective, economic analysis
      was based on costs and health outcomes from a 52 week randomised study comparing:
      (1) T 18 microg once daily + placebo twice daily (TP group); (2) T 18 microg once
      daily + S 25 microg/puff, 2 puffs twice daily (TS group); and (3) T 18 microg
      once daily + FS 250/25 microg/puff, 2 puffs twice daily (TFS group). The
      incremental cost effectiveness ratios (ICERs) were defined as incremental cost
      per exacerbation avoided, and per additional quality adjusted life year (QALY)
      between treatments. A combination of imputation and bootstrapping was used to
      quantify uncertainty, and extensive sensitivity analyses were performed. RESULTS:
      The average patient in the TP group generated CAN$2678 in direct medical costs
      compared with $2801 (TS group) and $4042 (TFS group). The TS strategy was
      dominated by TP and TFS. Compared with TP, the TFS strategy resulted in ICERs of
      $6510 per exacerbation avoided, and $243,180 per QALY gained. In those with
      severe COPD, TS resulted in equal exacerbation rates and slightly lower costs
      compared with TP. CONCLUSIONS: TFS had significantly better quality of life and
      fewer hospitalisations than patients treated with TP but these improvements in
      health outcomes were associated with increased costs. Neither TFS nor TS are
      economically attractive alternatives compared with monotherapy with T.

PMID- 18621986
TI  - Comparison of prophylactic use of midazolam, ketamine, and ketamine plus
      midazolam for prevention of shivering during regional anaesthesia: a randomized
      double-blind placebo controlled trial.
AB  - BACKGROUND: Regional anaesthesia, like general anaesthesia, influences the
      thermoregulatory process. The aim of the present study was to compare the
      efficacy of low-dose prophylactic midazolam with that of placebo, ketamine, and a
      combination of ketamine and midazolam in the prevention of shivering caused by
      regional anaesthesia. METHODS: In this double-blind study, 120 ASA I and II
      patients undergoing orthopaedic surgery were included. Subarachnoid anaesthesia
      was performed in all patients with bupivacaine 15 mg. The patients were randomly
      allocated to receive saline (Group C), ketamine 0.5 mg (Group K), midazolam 75
      microg kg(-1) (Group M), or ketamine 0.25 mg+midazolam 37.5 microg kg(-1) (Group
      KM). During surgery, a shivering score was recorded at 5 min intervals. Tympanic
      and axillary temperature were recorded at 10 min intervals during the
      perioperative period. RESULTS: After 15 min, the incidences of shivering in
      Groups C, M, K, and KM were 60%, 50%, 23.3%, 3.3%, respectively (P=0.000). The
      differences between Group KM and Groups M, K, and C were statistically
      significant (P=0.000, P=0.026, P<0.001, respectively). The number of patients
      with a shivering score of > or =3 was significantly higher in Group C compared
      with Groups M, K, and KM (8 vs 4, 1, and 0, respectively, P=0.040). CONCLUSIONS:
      Prophylactic use of ketamine 0.25 mg kg(-1)+midazolam 37.5 microg kg(-1) i.v. was
      more effective than ketamine 0.5 mg kg(-1) i.v. or midazolam 75 microg kg(-1)
      i.v. in preventing shivering developed during regional anaesthesia.

PMID- 18621987
TI  - A prospective double-blind randomized trial comparing intraluminal ethanol with
      heparinized saline for the prevention of catheter-associated bloodstream
      infection in immunosuppressed haematology patients.
AB  - OBJECTIVES: The aim of this study was to prospectively evaluate the use of
      intraluminal ethanol for the prevention of catheter-associated bloodstream
      infection (CABSI) in immunosuppressed haematology patients. PATIENTS AND METHODS:
      Patients receiving chemotherapy for haematological malignancy or haematopoietic
      cell transplantation were randomized in a double-blinded manner to receive either
      intraluminal 70% ethanol/water or heparinized saline locks on a daily basis
      throughout a prophylactic treatment period. The primary endpoint was an episode
      of CABSI (defined as 'bacteraemia in a febrile patient with a central venous
      catheter that was in use within the preceding 48 h and with no other identified
      focus of infection'). The trial was registered with the Australian Clinical
      Trials Register: number ACTRN012605000383662. RESULTS: There were 34 and 30
      prophylactic treatment periods in the ethanol and control groups, respectively.
      CABSI occurred in 3 (9%, 0.60/100 catheter-days) and 11 (37%, 3.11/100 catheter
      days) prophylactic treatment periods in the ethanol and control groups,
      respectively (OR = 0.18, 95% CI 0.05-0.65, P = 0.008). Eleven (32%) and 5 (17%)
      patients in the ethanol and control groups, respectively, remained afebrile
      throughout the prophylactic treatment (P = 0.18). CONCLUSIONS: The daily
      administration of ethanol locks into lumens of central venous catheters
      effectively reduces the incidence of CABSI.

PMID- 18621988
TI  - Thiorphan-induced survival and proliferation of rat thymocytes by activation of
      Akt/survivin pathway and inhibition of caspase-3 activity.
AB  - The activity of substance P (SP) in the rat thymus seems to be tightly controlled
      by its bioavailability. In this study, we provide evidence for the expression of
      the SP-degrading enzyme, neutral endopeptidase (NEP)/CD10, by rat thymocyte
      subsets, and we illustrate its involvement in the in vivo SP/neurokinin-1
      receptor (NK(1)R)-mediated regulation of thymocyte survival and proliferation.
      NEP/CD10 was expressed at both mRNA and protein levels on a substantial portion
      (45.5%) of CD5(+) thymocytes, namely on the CD4(+)CD8(+) (double positive; DP)
      and CD4(+) subsets. Continuous administration of thiorphan, a specific NEP/CD10
      inhibitor, by means of miniosmotic pumps, enhanced rat thymocyte preprotachykinin
      A (PPT-A) and NK(1)R mRNA expression as well as SP and NK(1)R protein levels in
      an NK(1)R-dependent manner. Thiorphan increased CD10(+)CD4(+) and CD10(+)DP
      thymocyte numbers, and an NK(1)R antagonist, (S)1-{2-[3(3-4-dichlorophenyl)-1-(3
      iso-propoxyphenylacetyl)-piperidine-3-yl]ethyl}-4-pheny-1
      azoniabicyclo[2.2.2]octane, chloride (SR140333), abrogated these stimulatory
      effects. In addition, the NEP/CD10 inhibitor stimulated interleukin (IL)-2
      production, IL-2 receptor alpha chain expression, and concanavalin A-induced
      proliferation of CD5(+) thymocytes, and it inhibited spontaneous and NK(1)R
      dependent thymocyte apoptosis. The thiorphan-protective antiapoptotic and
      proliferative effects involved the activation of Akt serine-threonine kinase,
      subsequent up-regulation of survivin mRNA, down-regulation of procaspase-3 mRNA
      levels, and suppression of caspase-3 activity, which were inhibited by SR140333
      and mimicked by exogenous SP administration. Overall, our findings suggest that
      by controlling SP availability, NEP/CD10 negatively regulates thymocyte
      homeostasis and development.

PMID- 18621989
TI  - The extensive nitration of neurofilament light chain in the hippocampus is
      associated with the cognitive impairment induced by amyloid beta in mice.
AB  - Tyrosine nitration of proteins at an extensive level is widely associated with
      the cognitive pathology induced by amyloid beta peptide (Abeta). However, the
      precise identity and explicit consequences of protein nitration have scarcely
      been addressed. In this study, we examined the detectable nitration of proteins
      in the hippocampus of mice with cognitive impairment (day 5) induced by the
      i.c.v. injection of Abeta(25-35) (day 0). The intensity of the nitration of
      proteins was inversely associated with the level of recognition memory in mice.
      The detectable tyrosine nitrations were revealed in proteins with a single size
      of approximately 70 kDa. The specific nitrated proteins at this size were
      identified using the liquid chromatography/mass spectrometry/mass spectrometry
      analysis and immunodetection methods. Intense nitration of the neurofilament
      light chain (NFL) was observed. The increased nitration of NFL was associated
      with its serine hyperphosphorylation and weak interaction with the nuclear
      distribution element-like, a protein essential for the stable assembly of
      neurofilaments. No changes in cell numbers in the hippocampus were found (day 5)
      in mice that received Abeta(25-35) injections. These findings suggested that
      extensive nitration of NFL is associated with the Abeta-induced impairment of
      recognition memory in mice.

PMID- 18621990
TI  - Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen
      regulated transcriptional network.
AB  - Neuronal subtype specification in the vertebrate neural tube is one of the best
      studied examples of embryonic pattern formation. Distinct neuronal subtypes are
      generated in a precise spatial order from progenitor cells according to their
      location along the anterior-posterior and dorsal-ventral axes. Underpinning this
      organization is a complex network of multiple extrinsic and intrinsic factors.
      This review focuses on the molecular mechanisms and general strategies at play in
      ventral regions of the forming spinal cord, where sonic hedgehog-based morphogen
      signaling is a key determinant. We discuss recent advances in our understanding
      of these events and highlight unresolved questions.

PMID- 18621991
TI  - Working group report: the roles of glycans in hemostasis, inflammation and
      vascular biology.

PMID- 18621993
TI  - Chemoenzymatic synthesis, characterization, and application of glycopolymers
      carrying lactosamine repeats as entry inhibitors against influenza virus
      infection.
AB  - To control interspecies transmission of influenza viruses, it is essential to
      elucidate the molecular mechanisms of the interaction of influenza viruses with
      sialo-glycoconjugate receptors expressed on different host cells. Competitive
      inhibitors containing mimetic receptor carbohydrates that prevent virus entry may
      be useful tools to address such issues. We chemoenzymatically synthesized and
      characterized the glycopolymers that were carrying terminal 2,6-sialic acid on
      lactosamine repeats as influenza virus inhibitors. In vitro and in vivo infection
      experiments using these glycopolymers demonstrated marked differences in
      inhibitory activity against different species of viruses. Human viruses,
      including clinically isolated strains, were consistently inhibited by
      glycopolymers carrying lactosamine repeats with higher activity than those
      containing a single lactosamine. A swine virus also showed the same recognition
      properties as those from human hosts. In contrast, avian and equine viruses were
      not inhibited by any of the glycopolymers examined carrying single, tandem, or
      triplet lactosamine repeats. Hemagglutination inhibition and solid-phase binding
      analyses indicated that binding affinity of glycopolymers with influenza viruses
      contributes dominantly to the inhibitory activity against viral infection.
      Sequence analysis and molecular modeling of human viruses indicated that specific
      amino acid substitutions on hemagglutinin may affect binding affinity of
      glycopolymers carrying lactosamine repeats with viruses. In conclusion,
      glycopolymers carrying lactosamine repeats of different lengths are useful to
      define molecular mechanisms of virus recognition. The core carbohydrate portion
      as well as sialyl linkages on the receptor glycoconjugate may affect host cell
      recognition of human and swine viruses.

PMID- 18621994
TI  - Characteristics of 234 dog bite incidents in Ireland during 2004 and 2005.
AB  - Information was obtained by telephone interview from 100 dog owners whose dog had
      bitten a person, and from 134 victims of bites by a dog not owned by the victim.
      Three-quarters of the victims were female and aged from 21 to 60 years. The
      majority of the dogs were owned, male, two to six years old, over 10 kg in
      bodyweight and belonged to the popular breeds: collies, cocker/springer spaniels,
      terrier breeds, Jack Russell terriers, German shepherd dogs, golden retrievers
      and crossbreeds. The numbers of bites by the different breeds indicated that
      those that inflicted the most bites were the popular breeds rather than the
      breeds with any greater propensity to bite. Most attacks were rapid single bites
      and in 50 per cent of the cases, neither the owner nor the victim was able to
      identify any signal of the dog's intention to bite. Overall, 21 per cent of the
      incidents were rated as 'serious' and 2 per cent as 'life threatening'. One fifth
      of the dogs were euthanased as a result of the incident. Half the incidents
      required professional medical assistance for the victim. Almost half the
      incidents took place while the victim was walking or passing close to the dog's
      territory, or while the victim was interacting with the dog at home.

PMID- 18621992
TI  - Strategies for carbohydrate recognition by the mannose 6-phosphate receptors.
AB  - The two members of the P-type lectin family, the 46 kDa cation-dependent mannose
      6-phosphate receptor (CD-MPR) and the 300 kDa cation-independent mannose 6
      phosphate receptor (CI-MPR), are ubiquitously expressed throughout the animal
      kingdom and are distinguished from all other lectins by their ability to
      recognize phosphorylated mannose residues. The best-characterized function of the
      MPRs is their ability to direct the delivery of approximately 60 different newly
      synthesized soluble lysosomal enzymes bearing mannose 6-phosphate (Man-6-P) on
      their N-linked oligosaccharides to the lysosome. In addition to its intracellular
      role in lysosome biogenesis, the CI-MPR, but not the CD-MPR, participates in a
      number of other biological processes by interacting with various molecules at the
      cell surface. The list of extracellular ligands recognized by this
      multifunctional receptor has grown to include a diverse spectrum of Man-6-P
      containing proteins as well as several non-Man-6-P-containing ligands. Recent
      structural studies have given us a clearer view of how these two receptors use
      related, but yet distinct, approaches in the recognition of phosphomannosyl
      residues.

PMID- 18621995
TI  - Patterns of lesions of bovine tuberculosis in wild red deer and wild boar.
AB  - The data obtained from a survey of Mycobacterium bovis infection in wild red deer
      (Cervus elaphus) and wild boar (Sus scrofa) conducted in France in the 2005/06
      hunting season were used to describe and quantify the pathological findings in
      the two species. The red deer had caseous abscessed lesions in their organs and
      lymph nodes, whereas in the wild boar the lesions were predominantly
      caseocalcareous and occurred mainly in the lymph nodes. The severity of the gross
      tuberculosis-like lesions was estimated on the basis of a numerical score. The
      significant difference between the distribution of the scores in the two species
      indicated that the disease was more serious in the red deer than in the wild
      boar. Unlike the red deer, the wild boar did not show a generalised pattern of
      disease. Among the lymph nodes examined systematically, gross lesions were most
      frequently observed in the mesenteric lymph nodes in the red deer and in the
      retropharyngeal lymph nodes in the wild boar. In both species, the presence of
      gross lesions showed the closest agreement with the isolation of M bovis from the
      same lymph nodes. The different patterns of the lesions of tuberculosis in the
      two species suggest that red deer might play an important role in the
      intraspecies and interspecies dissemination of the infection, whereas in wild
      boar the spread of the infection would be more likely to be restricted to other
      wild boar.

PMID- 18621996
TI  - B-mode and colour Doppler ultrasonography of the milk vein in 29 healthy Swiss
      braunvieh cows.
AB  - The morphology and diameter of the milk vein of 29 healthy Swiss braunvieh cows
      and the velocity of blood flow through it was measured by colour Doppler
      ultrasonography before and 10 minutes after they had been sedated with 0.03 mg/kg
      xylazine. The milk vein was situated immediately under the skin. It had a
      diameter of 0.8 to 1.6 cm and valves were visible in the milk vein of 12 of the
      cows. The spectral display appeared as a broad band structure with a wave-like
      course. The Doppler measurement point was 0.4 to 0.8 cm from the body surface.
      The diameter of the vein and the blood flow velocity did not differ significantly
      before and after the cows were sedated. The mean (sd) diameter of the milk vein
      before they were sedated was 1.3 (0.3) cm. The mean maximum blood flow velocity
      before they were sedated was 45.4 (12.5) cm/second, the mean velocity was 33.5
      (9.5) cm/second, and the mean minimum was 25.8 (11.6) cm/second. There were
      significant correlations between the blood flow velocities before and after the
      cows were sedated and between individual cow's blood flow velocities, with
      correlation coefficients ranging from 0.69 to 0.94.

PMID- 18621998
TI  - Serological evidence of West Nile virus in the great white pelican (Pelecanus
      onocrotalus).

PMID- 18621997
TI  - Evidence for transplacental transmission of the current wild-type strain of
      bluetongue virus serotype 8 in cattle.

PMID- 18621999
TI  - Primary ciliary dyskinesia and situs inversus in a young dog.

PMID- 18622000
TI  - Representing the profession.

PMID- 18622001
TI  - Disease importation and animal welfare.

PMID- 18622002
TI  - Dentistry and the curriculum.

PMID- 18622003
TI  - Representing the profession.

PMID- 18622004
TI  - Representing the profession.

PMID- 18622005
TI  - E-cadherin expression in canine cutaneous histiocytoma.

PMID- 18622006
TI  - Neurological disease in lambs and ewes grazing white clover.

PMID- 18622008
TI  - Glycogen phosphorylase BB could be a new circulating biomarker for detection of
      anthracycline cardiotoxicity.

PMID- 18622009
TI  - The Odor Awareness Scale: a new scale for measuring positive and negative odor
      awareness.
AB  - The Odor Awareness Scale (OAS) is a questionnaire designed to assess individual
      differences in awareness of odors in the environment. The theory that odor
      awareness can be distinguished in awareness of negative (to be avoided) odors and
      positive (to be approached) odors was tested using confirmatory factor analysis
      (CFA) on the 34-item questionnaire after completion by 525 respondents. CFA
      (after deletion of 2 items) showed good fit of the 2-factor theory, resulting in
      a positive awareness subscale (11 items, Cronbach's alpha = .77) and a negative
      awareness subscale (21 items, Cronbach's alpha = .80). Furthermore, reports of
      sickness from environmental odors were correlated with the negative odor
      awareness factor, not the positive odor awareness factor. Respondents scoring
      high on the overall sum score of the OAS showed significantly better olfactory
      performance on an odor perception test battery than respondents with a low score.
      These results suggest a causal relation between awareness of potentially negative
      odors, olfactory performance and experiencing health effects from environmental
      odor exposure, that warrants further investigation.

PMID- 18622010
TI  - Reasoning anomalies associated with delusions in schizophrenia.
AB  - Deluded people differ from nondeluded controls on attributional style
      questionnaires and probabilistic-reasoning and theory-of-mind (ToM) tasks. No
      study to date has examined the relations between these 3 reasoning anomalies in
      the same individuals so as to evaluate their functional independence and
      potentially inform theories of delusion formation. We did so in 35 schizophrenic
      patients with a history of delusions, 30 of whom were currently deluded, and 34
      healthy controls. Compared with healthy controls, patients showed (a) a jumping
      to-conclusions bias and a bias to overadjust when confronted with a change of
      evidence on probabilistic-reasoning tasks, (b) an excessive externalizing
      attributional bias, and (c) performance deficits on 3 ToM tasks. Probabilistic
      reasoning and ToM measures correlated, while attributional-bias scores were
      independent of other task measures. A general proneness to delusional ideation
      correlated with probabilistic-reasoning and ToM measures, while externalizing
      bias was unrelated to the study measures of delusional ideation. Personalizing
      bias associated specifically with paranoia across the clinical and nonclinical
      participants. Findings are consistent with a common underlying mechanism in
      schizophrenia which contributes to the anomalies on probabilistic-reasoning and
      ToM tasks associated with delusions. We speculate that this mechanism is
      impairment of the normal capacity to inhibit "perceived reality" (the evidence of
      our senses), a capacity that evolved as part of the "social brain" to facilitate
      intersubjective communication within a shared reality.

PMID- 18622011
TI  - 'Ready. Set. ACTION!' A theater-based obesity prevention program for children: a
      feasibility study.
AB  - This study examined the feasibility of implementing an innovative theater-based
      after-school program, 'Ready. Set. ACTION!', to reach ethnically diverse and low
      income children and their parents with obesity prevention messages. The study
      population included 96 children and 61 parents. Children were in fourth to sixth
      grade and 41% were overweight at baseline. Program impact was evaluated with a
      pre/post-randomized controlled study design, but a major focus was placed on the
      process evaluation conducted in the intervention schools. Intervention children
      and parents reported high program satisfaction and that they had made changes or
      intended to make positive changes in their behaviors due to program
      participation. However, few meaningful differences between the intervention and
      control conditions were found at follow-up. Thus, the combined process and impact
      evaluation results suggest that the intervention was effective in leading to
      increased awareness of the need for behavioral change, but was not powerful
      enough on its own to lead to behavioral change. From this feasibility study, we
      concluded that Ready. Set. ACTION! offers promise as a creative intervention
      strategy. The next research step may be to incorporate theater-based programs
      into more comprehensive school-based interventions, with both educational and
      environmental components, and evaluate program impact.

PMID- 18622012
TI  - Burnout in European family doctors: the EGPRN study.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of burnout,
      and of associated factors, amongst family doctors (FDs) in European countries.
      Methodology. A cross-sectional survey of FDs was conducted using a custom
      designed and validated questionnaire which incorporated the Maslach Burnout
      Inventory Human Services Survey (MBI-HSS) as well as questions about demographic
      factors, working experience, health, lifestyle and job satisfaction. MBI-HSS
      scores were analysed in the three dimensions of emotional exhaustion (EE),
      depersonalization (DP) and personal accomplishment (PA). RESULTS: Almost 3500
      questionnaires were distributed in 12 European countries, and 1393 were returned
      to give a response rate of 41%. In terms of burnout, 43% of respondents scored
      high for EE burnout, 35% for DP and 32% for PA, with 12% scoring high burnout in
      all three dimensions. Just over one-third of doctors did not score high for
      burnout in any dimension. High burnout was found to be strongly associated with
      several of the variables under study, especially those relative to respondents'
      country of residence and European region, job satisfaction, intention to change
      job, sick leave utilization, the (ab)use of alcohol, tobacco and psychotropic
      medication, younger age and male sex. CONCLUSIONS: Burnout seems to be a common
      problem in FDs across Europe and is associated with personal and workload
      indicators, and especially job satisfaction, intention to change job and the
      (ab)use of alcohol, tobacco and medication. The study questionnaire appears to be
      a valid tool to measure burnout in FDs. Recommendations for employment conditions
      of FDs and future research are made, and suggestions for improving the instrument
      are listed.

PMID- 18622014
TI  - HDAC1 promotes liver proliferation in young mice via interactions with C/EBPbeta.
AB  - HDAC1 (histone deacetylase 1) regulates a number of biological processes in
      cells. Our previous studies revealed that HDAC1 inhibits proliferation of the
      livers in old mice. We have surprisingly observed that HDAC1 is also increased in
      young livers proliferating after partial hepatectomy (PH) and in human liver
      tumors. Increased levels of HDAC1 after PH lead to its interaction with a member
      of the C/EBP family, C/EBPbeta, which is also elevated after PH. At early time
      points after PH, the HDAC1-C/EBPbeta complex binds to the C/EBPalpha promoter and
      represses expression of C/EBPalpha. A detailed analysis of the role of HDAC1 and
      C/EBPbeta proteins in the regulation of C/EBPalpha promoter showed that, whereas
      C/EBPbeta alone activates the promoter, HDAC1 represses the promoter in a
      C/EBPbeta-dependent manner. The inhibition of HDAC1 in the livers of young mice
      inhibits liver proliferation after PH, which is associated with high levels of
      C/EBPalpha. Consistent with the positive role of HDAC1-C/EBPbeta complexes in
      liver proliferation, we have found that the CUGBP1-HDAC1-C/EBPbeta pathway is
      activated in human tumor liver samples, suggesting that HDAC1-C/EBPbeta complexes
      are involved in the development of liver tumors. The causal role of the CUGBP1
      HDAC1 pathway in liver proliferation was examined in CUGBP1 transgenic mice,
      which display high levels of the CUGBP1-eIF2 complex. We have demonstrated that
      elevation of the HDAC1-C/EBPbeta complexes in CUGBP1 transgenic mice reduces
      expression of C/EBPalpha and increases the rate of liver proliferation. Thus,
      these studies have identified a new pathway that promotes liver proliferation in
      young mice and might contribute to the malignant transformations in the liver.

PMID- 18622013
TI  - Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: a novel
      paradigm for receptor cooperativity.
AB  - Proteinase-activated receptor 2 (PAR2), a seven-transmembrane G protein-coupled
      receptor, is activated at inflammatory sites by proteolytic cleavage of its
      extracellular N terminus by trypsin-like enzymes, exposing a tethered, receptor
      activating ligand. Synthetic agonist peptides (AP) that share the tethered ligand
      sequence also activate PAR2, often measured by Ca2+ release. PAR2 contributes to
      inflammation through activation of NF-kappaB-regulated genes; however, the
      mechanism by which this occurs is unknown. Overexpression of human PAR2 in
      HEK293T cells resulted in concentration-dependent, PAR2 AP-inducible NF-kappaB
      reporter activation that was protein synthesis-independent, yet blocked by
      inhibitors that uncouple Gi proteins or sequester intracellular Ca2+. Because
      previous studies described synergistic PAR2- and TLR4-mediated cytokine
      production, we hypothesized that PAR2 and TLR4 might interact at the level of
      signaling. In the absence of TLR4, PAR2-induced NF-kappaB activity was inhibited
      by dominant negative (DN)-TRIF or DN-TRAM constructs, but not by DN-MyD88,
      findings confirmed using cell-permeable, adapter-specific BB loop blocking
      peptides. Co-expression of TLR4/MD-2/CD14 with PAR2 in HEK293T cells led to a
      synergistic increase in AP-induced NF-kappaB signaling that was MyD88-dependent
      and required a functional TLR4, despite the fact that AP exhibited no TLR4
      agonist activity. Co-immunoprecipitation of PAR2 and TLR4 revealed a physical
      association that was AP-dependent. The response to AP or lipopolysaccharide was
      significantly diminished in TLR4(-/-) and PAR2(-/-) macrophages, respectively,
      and SW620 colonic epithelial cells exhibited synergistic responses to co
      stimulation with AP and lipopolysaccharide. Our data suggest a unique interaction
      between two distinct innate immune response receptors and support a novel
      paradigm of receptor cooperativity in inflammatory responses.

PMID- 18622015
TI  - HDAC1 cooperates with C/EBPalpha in the inhibition of liver proliferation in old
      mice.
AB  - Epigenetic control of liver proliferation involves cooperation between
      transcription factors and chromatin-remodeling proteins. In this work, we found
      that the levels of HDAC1 (histone deacetylase 1) are increased in quiescent
      livers of old mice. The elevation of HDAC1 in liver is mediated by the RNA
      binding protein CUGBP1. We found that the age-associated CUGBP1-eIF2 complex
      binds to the 5' region of HDAC1 mRNA and increases translation of HDAC1 in the
      liver. Further analyses showed that CUGBP1 also increases expression of HDAC1 in
      cultured cells, in the livers of CUGBP1 transgenic mice, and in the livers of
      mice injected with cyclin D3, which enhances the formation of the CUGBP1-eIF2
      complex. In livers of old mice, HDAC1 interacts with the transcription factor
      C/EBPalpha and is recruited by this protein to E2F-dependent promoters as a
      component of high M(r) C/EBPalpha-Brm complexes. The recruitment of HDAC1 to c
      Myc and FoxM1B promoters leads to deacetylation of histone H3 at Lys-9 on these
      E2F-dependent promoters. We show that HDAC1 is an important mediator of growth
      inhibitory activity of C/EBPalpha and that small interfering RNA-mediated
      inhibition of HDAC1 reduces the ability of C/EBPalpha to inhibit cell
      proliferation. In addition, we have found that both elevation of HDAC1 and
      interaction of C/EBPalpha with HDAC1 are controlled by cyclin D3-dependent
      mechanisms. Treatment of old mice with growth hormone, which reduces cyclin D3
      levels, leads to the reduction of the CUGBP1-eIF2 complex, normalization of HDAC1
      levels, and inhibition of interactions of HDAC1 with C/EBPalpha-Brm complexes.
      Thus, our data demonstrate that translational elevation of HDAC1 in livers of old
      mice is involved in the assembly of high M(r) protein-protein complexes that
      inhibit liver proliferation.

PMID- 18622016
TI  - Ca2+/calmodulin-dependent protein kinase II-dependent remodeling of Ca2+ current
      in pressure overload heart failure.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity is increased in
      heart failure (HF), a syndrome characterized by markedly increased risk of
      arrhythmia. Activation of CaMKII increases peak L-type Ca(2+) current (I(Ca)) and
      slows I(Ca) inactivation. Whether these events are linked mechanistically is
      unknown. I(Ca) was recorded in acutely dissociated subepicardial and
      subendocardial murine left ventricular (LV) myocytes using the whole cell patch
      clamp method. Pressure overload heart failure was induced by surgical
      constriction of the thoracic aorta. I(Ca) density was significantly larger in
      subepicardial myocytes than in subendocardial/myocytes. Similar patterns were
      observed in the cell surface expression of alpha1c, the channel pore-forming
      subunit. In failing LV, I(Ca) density was increased proportionately in both cell
      types, and the time course of I(Ca) inactivation was slowed. This typical pattern
      of changes suggested a role of CaMKII. Consistent with this, measurements of
      CaMKII activity revealed a 2-3-fold increase (p < 0.05) in failing LV. To test
      for a causal link, we measured frequency-dependent I(Ca) facilitation. In HF
      myocytes, this CaMKII-dependent process could not be induced, suggesting already
      maximal activation. Internal application of active CaMKII in failing myocytes did
      not elicit changes in I(Ca). Finally, CaMKII inhibition by internal diffusion of
      a specific peptide inhibitor reduced I(Ca) density and inactivation time course
      to similar levels in control and HF myocytes. I(Ca) density manifests a
      significant transmural gradient, and this gradient is preserved in heart failure.
      Activation of CaMKII, a known pro-arrhythmic molecule, is a major contributor to
      I(Ca) remodeling in load-induced heart failure.

PMID- 18622018
TI  - A functional peroxisome proliferator-activated receptor-gamma ligand-binding
      domain is not required for adipogenesis.
AB  - The nuclear hormone receptor peroxisome proliferator-activated receptor-gamma
      (PPARgamma) is the central regulator of adipogenesis. Although it is the target
      for several drugs that function as agonist activators, a high affinity endogenous
      ligand for this receptor that is involved in regulating adipogenesis has yet to
      be identified. Here, we investigated the requirement for ligand activation of
      PPARgamma in fat cell differentiation, taking advantage of a natural mutant of
      this receptor that does not bind or become activated by any known natural or
      synthetic ligand. When ectopically expressed in PPARgamma-null fibroblasts, this
      Q286P allele was able to strongly promote morphological adipogenesis, without any
      significant difference compared with wild-type PPARgamma. In addition, no
      significant differences were found in the expression of several adipogenic genes
      between the wild-type and Q286P mutant alleles. To extend our studies to an in
      vivo setting, we performed subcutaneous injections of PPARgamma-expressing
      fibroblasts into nude mice. We found that both wild-type and Q286P mutant
      expressing fibroblasts were able to generate fat pads in the mice. These results
      suggest that the binding and activation of PPARgamma by agonist ligands may not
      be required for adipogenesis under physiological conditions.

PMID- 18622017
TI  - Binding of recombinant but not endogenous prion protein to DNA causes DNA
      internalization and expression in mammalian cells.
AB  - Recombinant prion protein, rPrP, binds DNA. Both the KKRPK motif and the
      octapeptide repeat region of rPrP are essential for maximal binding. rPrP with
      pathogenic insertional mutations binds more DNA than wild-type rPrP. DNA promotes
      the aggregation of rPrP and protects its N terminus from proteinase K digestion.
      When rPrP is mixed with an expression plasmid and Ca(2+), the rPrP.DNA complex is
      taken up by mammalian cells leading to gene expression. In the presence of
      Ca(2+), rPrP by itself is also taken up by cells in a temperature- and
      pinocytosis-dependent manner. Cells do not take up rPrP(DeltaKKRPK), which lacks
      the KKRPK motif. Thus, rPrP is the carrier for DNA and the KKRPK motif is
      essential for its uptake. When mixed with DNA, a pentapeptide KKRPK, but not
      KKKKK, is sufficient for DNA internalization and expression. In contrast, whereas
      the normal cellular prion protein, PrP(C), on the cell surface can also
      internalize DNA, the imported DNA is not expressed. These findings may have
      relevance to the normal functions of PrP(C) and the pathogenic mechanisms of
      human prion disease.

PMID- 18622019
TI  - A fluorescent two-hybrid assay for direct visualization of protein interactions
      in living cells.
AB  - Genetic high throughput screens have yielded large sets of potential protein
      protein interactions now to be verified and further investigated. Here we present
      a simple assay to directly visualize protein-protein interactions in single
      living cells. Using a modified lac repressor system, we tethered a fluorescent
      bait at a chromosomal lac operator array and assayed for co-localization of
      fluorescent prey fusion proteins. With this fluorescent two-hybrid assay we
      successfully investigated the interaction of proteins from different subcellular
      compartments including nucleus, cytoplasm, and mitochondria. In combination with
      an S phase marker we also studied the cell cycle dependence of protein-protein
      interactions. These results indicate that the fluorescent two-hybrid assay is a
      powerful tool to investigate protein-protein interactions within their cellular
      environment and to monitor the response to external stimuli in real time.

PMID- 18622020
TI  - Lamellar bodies of human epidermis: proteomics characterization by high
      throughput mass spectrometry and possible involvement of CLIP-170 in their
      trafficking/secretion.
AB  - Lamellar bodies (LBs) are tubulovesicular secretory organelles of epithelial
      cells related to lysosomes. In the epidermis, they play a crucial role in
      permeability barrier homeostasis, secreting their contents, lipids, a variety of
      hydrolases, protease inhibitors, and antimicrobial peptides, in the upper
      keratinocyte layers. The identification of proteins transported in epidermal LBs
      is still far from complete, and the way their secretion is controlled unknown. In
      this study, we describe the first proteomics characterization by nano-LC-MS/MS of
      a fraction enriched in epidermal LBs. We identified 984 proteins, including
      proteins known or thought to be secreted by LBs. Moreover 31 proteins
      corresponded to lysosomal components further suggesting that LBs are a new class
      of secretory lysosomes. Many of the newly found proteins could play a role in the
      epidermal barrier and desquamation (one acid ceramidase-like protein,
      apolipoproteins, glycosidases, protease inhibitors, and peptidases) and in LB
      trafficking (e.g. Rab, Arf, and motor complex proteins). We focus here on CLIP
      170/restin, a protein that mediates interactions between organelles and
      microtubules. Western blotting confirmed the presence of CLIP-170 and its known
      effectors IQGAP1 and Cdc42 in the LB-enriched fraction. We showed, by confocal
      microscopy analysis of skin cryosections, that CLIP-170 was expressed in
      differentiated keratinocytes, first at the periphery of the nucleus then with a
      granular cytoplasmic labeling evocative of LBs. It was preferentially co
      localized with Cdc42 and with the known LB protein cathepsin D. CLIP-170 was also
      largely co-localized with Rab7. This study strongly suggests a new function for
      CLIP-170, its involvement together with Cdc42 and/or Rab7 in the intracellular
      trafficking of LBs, and provides evidence that nano-LC-MS/MS combined with
      monodimensional electrophoresis separation constitutes a powerful method for
      identifying proteins in a complex mixture such as subcellular structures.

PMID- 18622021
TI  - The role of macrophage in the pathogenesis of chronic cyclosporine-induced
      nephropathy.
AB  - BACKGROUND: Macrophages play diverse roles in tissue injury. We evaluated their
      role in cyclosporine (CsA)-induced renal injury by depletion with liposomal
      clodronate (CL). METHODS: Male Sprague Dawley rats were treated with CsA with or
      without CL treatment for 28 days. We assessed responses from the pathology and by
      measuring renal functions and levels of a proinflammatory cytokine (osteopontin),
      a profibrotic cytokine (betaig-h3), innate immune response markers (toll-like
      receptor 2 and MHC class II molecules), apoptotic cell death (deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labelling staining and caspase-3
      expression) and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG). RESULTS:
      Macrophage depletion with CL improved not only renal function but also
      histopathology compared with the CsA-treated rats. Osteopontin and betaig-h3
      levels increased significantly in CsA-treated rat kidneys, but CL treatment
      decreased both markers. Enhanced innate immune response and apoptotic cell death
      in CsA-treated rat kidney were decreased with CL. The increased rates of urinary
      8-OHdG excretion and the tubular expression of 8-OHdG produced by CsA treatment
      were reversed with CL treatment. CONCLUSIONS: Thus, infiltrating macrophages were
      involved in both nonimmunologic and immunologic injury and led to apoptotic cell
      death in this rat model of chronic CsA nephropathy.

PMID- 18622022
TI  - Increased incidence of infections following the late introduction of
      mycophenolate mofetil in renal transplant recipients.
AB  - BACKGROUND: Late introduction of mycophenolate mofetil (MMF) is used in renal
      transplant patients to allow calcineurin inhibitor (CNI) withdrawal. This change
      in treatment may alter the immunosuppressive load predisposing patients to
      infections. To assess this we have analysed infection rates in 30 consecutive
      patients with chronic allograft nephropathy commenced on MMF for CNI withdrawal.
      Methods and results. The study period was from 12 months pre-commencement to 12
      months post-commencement. At commencement, patient mean age was 51.2 +/- 12.9
      years and mean time post-transplant was 3170 +/- 2130 days. Estimated glomerular
      filtration rate (eGFR) at the start of the study period and at conversion was
      30.7 +/- 12.1 ml/min and 23.1 +/- 9.9 ml/min, respectively. The mean dose of MMF
      post-conversion was 1575 +/- 428 mg/day. Estimated GFR had stabilized at 12
      months post-conversion to 25.3 +/- 12.2 ml/min. There was a significant increase
      in infections following conversion: pre-conversion, 26.7% (8/30); post
      conversion, 66.6% (20/30) (chi(2) = 24.5, P < 0.0005). There was an inverse
      correlation between eGFR at conversion and infection rates post-conversion (r = 
      0.379, P = 0.039). There were no hospitalizations for infection pre-conversion
      and 6 patients (20%) were hospitalized post-conversion, for a total of 285 days
      (7-107). CONCLUSION: There is significant morbidity associated with an increased
      incidence of infection after late introduction of MMF at standard doses in renal
      transplant recipients. This risk may be related to GFR at the time of conversion.

PMID- 18622023
TI  - Twenty-one additional cases of familial renal glucosuria: absence of genetic
      heterogeneity, high prevalence of private mutations and further evidence of
      volume depletion.
AB  - INTRODUCTION: Familial renal glucosuria (FRG) is a rare renal tubular disorder
      caused by mutations within the SLC5A2 gene. It is characterized by persistent
      glucosuria in the absence of hyperglycaemia and any other signs of generalized
      tubular dysfunction. In small series of patients previously reported, the
      molecular and phenotypic findings in FRG families, including first hints of
      extracellular volume depletion and activation of the renin-angiotensin
      aldosterone system induced by natriuresis, have been described. We have now
      extended this analysis to another 21 consecutive cases from 17 pedigrees,
      including 11 cases with severe glucose excretion. METHODS: Mutation analysis was
      performed by direct sequencing of the genomic coding segments of the SLC5A2 gene.
      In two cases with severe glucosuria, basal plasma renin activity and serum
      aldosterone concentrations were determined. RESULTS: Within the 17 pedigrees, we
      have identified a total of 20 different SLC5A2 mutations. Fifteen have not been
      previously reported. In all glucosuric individuals tested, at least one SLC5A2
      mutation could be identified. Heterozygous individuals were found to have only
      mild glucose excretion whereas homozygous or compound heterozygous patients had
      severe glucosuria, ranging from 10 to 86.5 g/1.73 m(2)/24 h. In two patients of
      the latter group, basal plasma renin activity and serum aldosterone concentration
      were determined and found to be raised to an average of 4.6-fold and 3.1-fold of
      the upper limit of the normal range, respectively. Discussion. The identification
      of at least one mutated allele in every affected individual in this cohort of 17
      consecutively investigated families strongly suggests that genetic heterogeneity
      is not prevalent in FRG. Although 5 of the detected alleles have been described
      previously, 15 are novel, confirming that most mutations in FRG are private. Our
      finding of an activation of compensatory mechanisms for salt loss may warrant
      more detailed studies of long-term hormonal and metabolic imbalances in patients
      with FRG.

PMID- 18622024
TI  - Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis
      of tubular sodium reabsorption.
AB  - BACKGROUND: Obesity is associated with hypertension and glomerular
      hyperfiltration. A major mechanism responsible for the obesity-associated
      hypertension is renal salt retention. An increased glomerular filtration fraction
      (FF) is expected to raise postglomerular oncotic pressure and to increase
      proximal tubular sodium reabsorption. The aim of the present study was to verify
      whether obesity-associated hyperfiltration leads to increased postglomerular
      oncotic pressure and increased proximal sodium reabsorption. METHODS: Twelve
      obese subjects (BMI >36) and 19 lean subjects participated in the study. They
      underwent measurement of glomerular filtration rate (GFR), renal plasma flow
      (RPF) and fractional excretion of lithium (FE Li). RESULTS: GFR, RPF and FF were
      61%, 28% and 29% higher, respectively, in the obese than in the control group (P
      < 0.00001 for GFR, P < 0.005 for RPF and P < 0.00005 for FF). Half of the obese
      group had increased FF with increased GFR, while the other half had normal FF
      with high-normal or increased GFR. Postglomerular oncotic pressure was 13% higher
      (P < 0.03) and FE Li was 33% lower (P < 0.005) in the obese group with high FF
      than in the lean group. Postglomerular oncotic pressure and FE Li were normal in
      the obese group with normal FF. CONCLUSIONS: These results suggest that
      glomerular hyperfiltration may lead to increased proximal tubular sodium
      reabsorption in the obese.

PMID- 18622025
TI  - Thrombin enhances the production of monocyte chemoattractant protein-1 and
      macrophage inflammatory protein-2 in cultured rat glomerular epithelial cells.
AB  - BACKGROUND: Glomerular crescents play an important role in progressive glomerular
      injury. The lesions consist of epithelial cells, macrophages and deposits of
      fibrin and extracellular matrix. Monocyte chemoattractant protein-1 (MCP-1) and
      macrophage inflammatory protein-2 (MIP-2) are members of chemokine subfamilies.
      MCP-1 and MIP-2 are potent chemoattractant leukocyte cytokines, and they may be
      involved in crescent formation. Thrombin participates in fibrin formation. We
      hypothesized that thrombin stimulates the production of MCP-1 and MIP-2 by
      glomerular epithelial cells (GECs). METHODS: Cultured rat GECs from the 19th to
      the 24th passage were used. We incubated GECs with or without thrombin to examine
      the effect of thrombin on the production of MCP-1 and MIP-2. The levels of MCP-1
      and MIP-2 were measured in the cell supernatants by enzyme-linked immunosorbent
      assay (ELISA). The mRNA expressions of MCP-1 and MIP-2 were analysed by real-time
      reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the
      inhibitory effect of argatroban, a synthetic thrombin inhibitor, and prednisolone
      in the production of MCP-1 and MIP-2 stimulated by thrombin. RESULTS: Thrombin
      stimulated the production of MCP-1 and MIP-2 in a dose- and time-dependent
      manner. Thrombin also enhanced the mRNA expressions of MCP-1 and MIP-2 in the
      GECs. The stimulating effect of thrombin on the production of MCP-1 and MIP-2 was
      inhibited by the addition of argatroban or prednisolone. CONCLUSIONS: We
      demonstrated a novel role of thrombin: it stimulates the production of MCP-1 and
      MIP-2 by GECs. It is clinically important that the inhibition of these chemokines
      leads to the improvement of crescentic glomerulonephritis. Anti-thrombin drugs
      and prednisolone may be useful in treating crescentic glomerulonephritis.

PMID- 18622027
TI  - Effect of CYP2E1 gene deletion in mice on expression of microsomal epoxide
      hydrolase in response to VCD exposure.
AB  - Females are born with a finite number of primordial follicles. 4-Vinylcyclohexene
      diepoxide (VCD) is a metabolite formed by epoxidation of 4-vinylcyclohexene (VCH)
      via its two monoepoxides 1,2- and 7,8-4-vinylcyclohexene monoepoxide (VCM). VCD
      specifically destroys small preantral (primordial and small primary) follicles in
      the rodent ovary. The phase I enzyme, cytochrome P450 isoform 2E1 (CYP2E1) is
      involved in ovarian metabolism of VCM to VCD. Further, microsomal epoxide
      hydrolase (mEH) can detoxify VCD to an inactive tetrol (4-(1,2-dihydroxy)ethyl
      1,2-dihydroxycyclohexane). This study evaluated the effects of VCD-induced
      ovotoxicity on mEH in CYP2E1+/+ and -/- mice (129S(1)/SvImJ background strain)
      using a postnatal day 4 mouse whole ovary culture system. The hypothesis of our
      study is that there is a relationship between CYP2E1 and mEH gene expression in
      the mouse ovary. Relative to control, VCD exposure caused follicle loss (p <
      0.05) in ovaries from both genotypes; however, after 15 days, this loss was
      greater (p < 0.05) in CYP2E1+/+ ovaries. In a time course (2-15 days), relative
      to control, VCD (5 microM) caused an increase (p < 0.05) in mEH mRNA by 0.5-fold
      (day 10) and 1.84-fold (day 15) in CYP2E1-/- but not +/+ ovaries. 7,12
      Dimethylbenz[a]anthracene (DMBA) also destroys ovarian follicles but, unlike VCD,
      is bioactivated by mEH to an ovotoxic 3,4-diol-1,2-epoxide metabolite. Incubation
      of ovaries in increasing concentrations of DMBA (0.5-1 microM, 15 days) resulted
      in greater (p < 0.05) follicle loss in CYP2E1-/-, relative to +/+ ovaries. With
      greater mEH (CYP2E1-/-), increased follicle loss with DMBA (bioactivation) and
      decreased follicle loss with VCD (detoxification) support that ovarian expression
      of CYP2E1 and mEH may be linked.

PMID- 18622026
TI  - Ligand activation of peroxisome proliferator-activated receptor beta/delta
      (PPARbeta/delta) attenuates carbon tetrachloride hepatotoxicity by downregulating
      proinflammatory gene expression.
AB  - Peroxisome proliferator-activated receptor (PPAR) beta/delta-null mice exhibit
      exacerbated hepatotoxicity in response to administration of carbon tetrachloride
      (CCl(4)). To determine whether ligand activation of the receptor protects against
      chemical toxicity in the liver, wild-type and PPARbeta/delta-null mice were
      administered CCl(4) with or without coadministration of the highly specific
      PPARbeta/delta ligand GW0742. Biomarkers of liver toxicity, including serum
      alanine aminotransferase (ALT) and hepatic tumor necrosis factor (TNF) alpha
      mRNA, were significantly higher in CCl(4)-treated PPARbeta/delta-null mice
      compared to wild-type mice. Hepatic expression of TNF-like weak inducer of
      apoptosis receptor (TWEAKr) and S100 calcium-binding protein A6
      (S100A6/calcyclin), genes involved in nuclear factor kappa B signaling, was
      higher in the CCl(4)-treated PPARbeta/delta-null mice compared to wild-type mice.
      GW0742 treatment resulted in reduced serum ALT concentration and lower expression
      of CCl(4)-induced TNF-alpha, S100A6, monocyte chemoattractant protein-1 (MCP1),
      and TWEAKr in wild-type mice, and these effects were not observed in
      PPARbeta/delta-null mice. Expression of TNF-alpha was higher in PPARbeta/delta
      null primary hepatocytes in response to interleukin-1beta treatment compared to
      wild-type hepatocytes, but GW0742 did not significantly modulate TNF-alpha
      expression in hepatocytes from either genotype. While PPARbeta/delta-null hepatic
      stellate exhibited higher rates of proliferation compared to wild-type cells,
      GW0742 did not affect alpha-smooth muscle actin expression in these cells.
      Combined, these findings demonstrate that ligand activation of PPARbeta/delta
      protects against chemically induced hepatotoxicity by downregulating expression
      of proinflammatory genes. Hepatocytes and hepatic stellate cells do not appear to
      directly mediate the inhibitory effects of ligand activation of PPARbeta/delta in
      liver, suggesting the involvement of paracrine and autocrine events mediated by
      hepatic cells.

PMID- 18622028
TI  - Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol
      export from macrophages in vivo.
AB  - Eight proteins potentially involved in cholesterol efflux [ABCA1, ABCG1, CYP27A1,
      phospholipid transfer protein (PLTP), scavenger receptor type BI (SR-BI),
      caveolin-1, cholesteryl ester transfer protein, and apolipoprotein A-I (apoA-I)]
      were overexpressed alone or in combination in RAW 264.7 macrophages. When apoA-I
      was used as an acceptor, overexpression of the combination of ABCA1, CYP27A1,
      PLTP, and SR-BI (Combination I) enhanced the efflux by 4.3-fold. It was
      established that the stimulation of efflux was due to increased abundance of
      ABCA1 and increased apoA-I binding to non-ABCA1 sites on macrophages. This
      combination caused only a small increase of the efflux to isolated HDL. When HDL
      was used as an acceptor, overexpression of caveolin-1 or a combination of
      caveolin-1 and SR-BI (Combination II) was the most active, doubling the efflux to
      HDL, without affecting the efflux to apoA-I. When tested in the in vivo mouse
      model of cholesterol efflux, overexpression of ABCA1 and Combination I elevated
      cholesterol export from macrophages to plasma, liver, and feces, whereas
      overexpression of caveolin-1 or Combination II did not have an effect. We
      conclude that pathways of cholesterol efflux using apoA-I as an acceptor make a
      predominant contribution to cholesterol export from macrophages in vivo.

PMID- 18622029
TI  - Identification of diagnostic biomarkers for infection in premature neonates.
AB  - Infection is a leading cause of neonatal morbidity and mortality worldwide.
      Premature neonates are particularly susceptible to infection because of
      physiologic immaturity, comorbidity, and extraneous medical interventions.
      Additionally premature infants are at higher risk of progression to sepsis or
      severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial
      diagnosis is based upon clinical suspicion accompanied by nonspecific clinical
      signs and is confirmed upon positive microbiologic culture results several days
      after institution of empiric therapy. There exists a significant need for rapid,
      objective, in vitro tests for diagnosis of infection in neonates who are
      experiencing clinical instability. We used immunoassays multiplexed on
      microarrays to identify differentially expressed serum proteins in clinically
      infected and non-infected neonates. Immunoassay arrays were effective for
      measurement of more than 100 cytokines in small volumes of serum available from
      neonates. Our analyses revealed significant alterations in levels of eight serum
      proteins in infected neonates that are associated with inflammation, coagulation,
      and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor
      alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and
      its cognate receptor, and C-reactive protein were observed at statistically
      significant increased levels. Multivariate classifiers based on combinations of
      serum analytes exhibited better diagnostic specificity and sensitivity than
      single analytes. Multiplexed immunoassays of serum cytokines may have clinical
      utility as an adjunct for rapid diagnosis of infection and differentiation of
      etiologic agent in neonates with clinical decompensation.

PMID- 18622030
TI  - A key transcription cofactor on the nascent sex chromosomes of European tree
      frogs (Hyla arborea).
AB  - We show that MED15, a key component of the transcription complex Mediator, lies
      within the nonrecombining segment of nascent sex chromosomes in the male
      heterogametic Hyla arborea. Both X and Y alleles are expressed during embryonic
      development and differ by three frame-preserving indels (eight amino acids in
      total) within their glutamine-rich central part. These changes have the potential
      to affect the conformation of the Mediator complex and to activate genes in a sex
      specific way and might thus represent the first steps toward the acquisition of a
      male-specific function. Alternatively, they might result from an ancestral
      neutral polymorphism, with different alleles picked by chance on the X and Y
      chromosomes when MED15 was trapped in the nonrecombining segment.

PMID- 18622031
TI  - Complex network of Wnt signaling regulates neuronal migrations during
      Caenorhabditis elegans development.
AB  - Members of the Wnt family of secreted glycoproteins regulate many developmental
      processes, including cell migration. We and others have previously shown that the
      Wnts egl-20, cwn-1, and cwn-2 are required for cell migration and axon guidance.
      However, the roles in cell migration of all of the Caenorhabditis elegans Wnt
      genes and their candidate receptors have not been explored fully. We have
      extended our analysis to include all C. elegans Wnts and six candidate Wnt
      receptors: four Frizzleds, the sole Ryk family receptor LIN-18, and the Ror
      receptor tyrosine kinase CAM-1. We show that three of the Wnts, CWN-1, CWN-2, and
      EGL-20, play major roles in directing cell migrations and that all five Wnts
      direct specific cell migrations either by acting redundantly or by antagonizing
      each other's function. We report that all four Frizzleds function to direct Q
      descendant cell migrations, but only a subset of the putative Wnt receptors
      function in directing migrations of other cells. Finally, we find striking
      differences between the phenotypes of the Wnt quintuple and Frizzled quadruple
      mutants.

PMID- 18622032
TI  - Identity-by-descent estimation and mapping of qualitative traits in large,
      complex pedigrees.
AB  - Computing identity-by-descent sharing between individuals connected through a
      large, complex pedigree is a computationally demanding task that often cannot be
      done using exact methods. What I present here is a rapid computational method for
      estimating, in large complex pedigrees, the probability that pairs of alleles are
      IBD given the single-point genotype data at that marker for all individuals. The
      method can be used on pedigrees of essentially arbitrary size and complexity
      without the need to divide the individuals into separate subpedigrees. I apply
      the method to do qualitative trait linkage mapping using the nonparametric
      sharing statistic S(pairs). The validity of the method is demonstrated via
      simulation studies on a 13-generation 3028-person pedigree with 700 genotyped
      individuals. An analysis of an asthma data set of individuals in this pedigree
      finds four loci with P-values <10(-3) that were not detected in prior analyses.
      The mapping method is fast and can complete analyses of approximately 150
      affected individuals within this pedigree for thousands of markers in a matter of
      hours.

PMID- 18622033
TI  - Molecular evolution of the Pi-ta gene resistant to rice blast in wild rice (Oryza
      rufipogon).
AB  - Rice blast disease resistance to the fungal pathogen Magnaporthe grisea is
      triggered by a physical interaction between the protein products of the host R
      (resistance) gene, Pi-ta, and the pathogen Avr (avirulence) gene, AVR-pita. The
      genotype variation and resistant/susceptible phenotype at the Pi-ta locus of wild
      rice (Oryza rufipogon), the ancestor of cultivated rice (O. sativa), was surveyed
      in 36 locations worldwide to study the molecular evolution and functional
      adaptation of the Pi-ta gene. The low nucleotide polymorphism of the Pi-ta gene
      of O. rufipogon was similar to that of O. sativa, but greatly differed from what
      has been reported for other O. rufipogon genes. The haplotypes can be subdivided
      into two divergent haplogroups named H1 and H2. H1 is derived from H2, with
      nearly no variation and at a low frequency. H2 is common and is the ancestral
      form. The leucine-rich repeat (LRR) domain has a high pi(non)/pi(syn) ratio, and
      the low polymorphism of the Pi-ta gene might have primarily been caused by
      recurrent selective sweep and constraint by other putative physiological
      functions. Meanwhile, we provide data to show that the amino acid Ala-918 of H1
      in the LRR domain has a close relationship with the resistant phenotype. H1 might
      have recently arisen during rice domestication and may be associated with the
      scenario of a blast pathogen-host shift from Italian millet to rice.

PMID- 18622034
TI  - Integration of cytogenetic and genetic linkage maps unveils the physical
      architecture of tomato chromosome 2.
AB  - We report the integration of the linkage map of tomato chromosome 2 with a high
      density bacterial artificial chromosome fluorescence in situ hybridization (BAC
      FISH)-based cytogenetic map. The euchromatic block of chromosome 2 resides
      between 13 and 142 cM and has a physical length of 48.12 microm, with 1 microm
      equivalent to 540 kb. BAC-FISH resolved a pair of loci that were 3.7-3.9 Mb apart
      and were not resolved on the linkage map. Most of the regions had crossover
      densities close to the mean of approximately 200 kb/cM. Relatively hot and cold
      spots of recombination were unevenly distributed along the chromosome. The
      distribution of centimorgan/micrometer values was similar to the previously
      reported recombination nodule distribution along the pachytene chromosome. FISH
      based physical maps will play an important role in advanced genomics research for
      tomato, including map-based cloning of agronomically important traits and whole
      genome sequencing.

PMID- 18622035
TI  - Dissection of the genetic architecture of body weight in chicken reveals the
      impact of epistasis on domestication traits.
AB  - In this contribution, we study the genetic mechanisms leading to differences in
      the observed growth patterns of domesticated White Leghorn chickens and their
      wild ancestor the red jungle fowl. An epistatic QTL analysis for several body
      weight measures from hatch to adulthood confirms earlier findings that
      polymorphisms at >15 loci contribute to body-weight determination in an F(2)
      intercross between these populations and that many loci are involved in complex
      genetic interactions. Here, we use a new genetic model to decompose the genetic
      effects of this multilocus epistatic genetic network. The results show how the
      functional modeling of genetic effects provides new insights into how genetic
      interactions in a large set of loci jointly contribute to phenotypic expression.
      By exploring the functional effects of QTL alleles, we show that some alleles can
      display temporal shifts in the expression of genetic effects due to their
      dependencies on the genetic background. Our results demonstrate that the effects
      of many genes are dependent on genetic interactions with other loci and how their
      involvement in the domestication process relies on these interactions.

PMID- 18622036
TI  - Chromosomal rearrangement inferred from comparisons of 12 Drosophila genomes.
AB  - The availability of 12 complete genomes of various species of genus Drosophila
      provides a unique opportunity to analyze genome-scale chromosomal rearrangements
      among a group of closely related species. This article reports on the comparison
      of gene order between these 12 species and on the fixed rearrangement events that
      disrupt gene order. Three major themes are addressed: the conservation of
      syntenic blocks across species, the disruption of syntenic blocks (via
      chromosomal inversion events) and its relationship to the phylogenetic
      distribution of these species, and the rate of rearrangement events over
      evolutionary time. Comparison of syntenic blocks across this large genomic data
      set confirms that genetic elements are largely (95%) localized to the same Muller
      element across genus Drosophila species and paracentric inversions serve as the
      dominant mechanism for shuffling the order of genes along a chromosome. Gene
      order scrambling between species is in accordance with the estimated evolutionary
      distances between them and we find it to approximate a linear process over time
      (linear to exponential with alternate divergence time estimates). We find the
      distribution of synteny segment sizes to be biased by a large number of small
      segments with comparatively fewer large segments. Our results provide estimated
      chromosomal evolution rates across this set of species on the basis of whole
      genome synteny analysis, which are found to be higher than those previously
      reported. Identification of conserved syntenic blocks across these genomes
      suggests a large number of conserved blocks with varying levels of embryonic
      expression correlation in Drosophila melanogaster. On the other hand, an analysis
      of the disruption of syntenic blocks between species allowed the identification
      of fixed inversion breakpoints and estimates of breakpoint reuse and lineage
      specific breakpoint event segregation.

PMID- 18622038
TI  - Linkage disequilibrium and persistence of phase in Holstein-Friesian, Jersey and
      Angus cattle.
AB  - When a genetic marker and a quantitative trait locus (QTL) are in linkage
      disequilibrium (LD) in one population, they may not be in LD in another
      population or their LD phase may be reversed. The objectives of this study were
      to compare the extent of LD and the persistence of LD phase across multiple
      cattle populations. LD measures r and r(2) were calculated for syntenic marker
      pairs using genomewide single-nucleotide polymorphisms (SNP) that were genotyped
      in Dutch and Australian Holstein-Friesian (HF) bulls, Australian Angus cattle,
      and New Zealand Friesian and Jersey cows. Average r(2) was approximately 0.35,
      0.25, 0.22, 0.14, and 0.06 at marker distances 10, 20, 40, 100, and 1000 kb,
      respectively, which indicates that genomic selection within cattle breeds with
      r(2) >or= 0.20 between adjacent markers would require approximately 50,000 SNPs.
      The correlation of r values between populations for the same marker pairs was
      close to 1 for pairs of very close markers (<10 kb) and decreased with increasing
      marker distance and the extent of divergence between the populations. To find
      markers that are in LD with QTL across diverged breeds, such as HF, Jersey, and
      Angus, would require approximately 300,000 markers.

PMID- 18622040
TI  - Alpha-synuclein A30P point-mutation generates age-dependent nigrostriatal
      deficiency in mice.
AB  - Lewy bodies are mainly composed of alpha-synuclein (SNCA) and specific mutations
      in SNCA gene are related to familial forms of Parkinson's disease (PD). The
      purpose of our study was to generate a mouse line with A30P knock-in point
      mutation in SNCA gene and to test if a single point-mutation is able to turn
      otherwise normal SNCA into a toxic form. The behavioral profile of SNCA A30P mice
      was followed for 16 months. Generally, these mice are healthy and viable without
      any obvious abnormalities. Starting from the age of 13 months mice developed a
      significant deficit in motor performance tests related to nigrostriatal function
      (ink-test and beam walk). In other tests (motility boxes, rotarod) mice
      continuously performed normally. Moreover, SNCA A30P mice expressed the altered
      sensitivity to VMAT2 inhibitor reserpine, possibly reflecting a functional
      deficiency of dopamine. Indeed, mice at 15 months of age had significantly
      reduced levels of dopamine and its major metabolite DOPAC in the striatum, and
      reduced levels of dopamine in the mesolimbic system. The present study confirms
      that SNCA plays an important role in the development of PD and an insertion of a
      single point mutation is sufficient to generate age-related decline in specific
      motor performance. The generated mouse line has a potential to become a model for
      PD with comparable time course and phenotype.

PMID- 18622039
TI  - Phosphorylation of endothelial nitric-oxide synthase regulates superoxide
      generation from the enzyme.
AB  - In the vasculature, nitric oxide (NO) is generated by endothelial NO synthase
      (eNOS) in a calcium/calmodulin-dependent reaction. With oxidative stress, the
      critical cofactor BH(4) is depleted, and NADPH oxidation is uncoupled from NO
      generation, leading to production of (O(2)*). Although phosphorylation of eNOS
      regulates in vivo NO generation, the effects of phosphorylation on eNOS coupling
      and O(2)* generation are unknown. Therefore, we phosphorylated recombinant BH(4)
      free eNOS in vitro using native kinases and determined O(2)* generation using EPR
      spin trapping. Phosphorylation of Ser-1177 by Akt led to an increase (>50%) in
      maximal O(2)* generation from eNOS. Moreover, Ser-1177 phosphorylation greatly
      altered the Ca(2+) sensitivity of eNOS, such that O(2)* generation became largely
      Ca(2+)-independent. In contrast, phosphorylation of eNOS at Thr-495 by protein
      kinase Calpha (PKCalpha) had no effect on maximum activity or calcium sensitivity
      but decreased calmodulin binding and increased association with caveolin. In
      endothelial cells, eNOS-dependent O(2)* generation was stimulated by vascular
      endothelial growth factor that induced phosphorylation of Ser-1177. With PKC
      activation that led to phosphorylation of Thr-495, no inhibition of O(2)*
      generation occurred. As such, phosphorylation of eNOS at Ser-1177 is pivotal in
      the direct regulation of O(2)* and NO generation, altering both the Ca(2+)
      sensitivity of the enzyme and rate of product formation, whereas phosphorylation
      of Thr-495 indirectly affects this process through regulation of the calmodulin
      and caveolin interaction. Thus, Akt-mediated phosphorylation modulates eNOS
      uncoupling and greatly increases O(2)* generation from the enzyme at low Ca(2+)
      concentrations, and PKCalpha-mediated phosphorylation alters the sensitivity of
      the enzyme to other negative regulatory signals.

PMID- 18622037
TI  - Polytene chromosomal maps of 11 Drosophila species: the order of genomic
      scaffolds inferred from genetic and physical maps.
AB  - The sequencing of the 12 genomes of members of the genus Drosophila was taken as
      an opportunity to reevaluate the genetic and physical maps for 11 of the species,
      in part to aid in the mapping of assembled scaffolds. Here, we present an
      overview of the importance of cytogenetic maps to Drosophila biology and to the
      concepts of chromosomal evolution. Physical and genetic markers were used to
      anchor the genome assembly scaffolds to the polytene chromosomal maps for each
      species. In addition, a computational approach was used to anchor smaller
      scaffolds on the basis of the analysis of syntenic blocks. We present the
      chromosomal map data from each of the 11 sequenced non-Drosophila melanogaster
      species as a series of sections. Each section reviews the history of the polytene
      chromosome maps for each species, presents the new polytene chromosome maps, and
      anchors the genomic scaffolds to the cytological maps using genetic and physical
      markers. The mapping data agree with Muller's idea that the majority of
      Drosophila genes are syntenic. Despite the conservation of genes within
      homologous chromosome arms across species, the karyotypes of these species have
      changed through the fusion of chromosomal arms followed by subsequent
      rearrangement events.

PMID- 18622041
TI  - Activation of endocannabinoid transmission induces antidepressant-like effects in
      rats.
AB  - Recent reports indicate that endocannabinoid (eCB) system may be involved in
      depression and in the antidepressant-like activity demonstrated in experimental
      models. The present study examined the effects of the eCB uptake inhibitor 4
      hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404; 0.1-3 mg/kg), the fatty
      acid amide hydrolase (FAAH) inhibitor cyclohexylcarbamic acid 3-carbamoylbiphenyl
      3-yl ester (URB597; 0.03-0.3 mg/kg), the cannabinoid CB(1) receptor agonist (-)
      cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)
      cyclohexanol (CP55,940; 0.03-0.3 mg/kg) and the CB(1) receptor antagonist
      rimonabant (0.3-3 mg/kg) on immobility time in the forced swim test (FST) in
      rats. Moreover, the effects of AM404, CP55,940 and URB597 on the antidepressant
      like activity of imipramine and citalopram in the FST were also examined. We
      found that AM404 (0.3-3 mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.1-0.3 mg/kg)
      reduced the immobility time of rats, while rimonabant (0.3-3 mg/kg) was inactive
      in this respect. We also observed that the anti-immobility effects of AM404 (1
      mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.3 mg/kg), but not of imipramine (30
      mg/kg), were blocked by rimonabant (3 mg/kg). In another set of experiments we
      showed that the inactive dose of AM404 (0.1 mg/kg) potentiated the effects of the
      inactive doses of imipramine (15 mg/kg) or citalopram (30 mg/kg), while CP55,940
      (0.03 mg/kg) and URB597 (0.03 mg/kg) enhanced the effect of imipramine only. None
      of the drugs studied, given alone or in combination, increased the basal
      locomotor activity of rats. Our results indicate that activation of the eCB
      system induces antidepressant-like effects in the FST in rats, and that these
      effects are mediated by CB(1) receptors. Moreover, they also indicate that agents
      activating eCB transmission enhance the anti-immobility responses to
      antidepressant drugs.

PMID- 18622042
TI  - A search for colocalization of serotonin 5-HT2A and 5-HT1A receptors in the rat
      medial prefrontal and entorhinal cortices--immunohistochemical studies.
AB  - Recently developed antipsychotic drugs ameliorating the negative symptoms of
      schizophrenia act not only on dopamine D2 receptors but also on serotonin 2A (5
      HT2A) and 1A (5-HT1A) receptors in specific regions of the cerebral cortex. Since
      it is not yet known whether serotonin 5-HT1A and 5-HT2A receptors coexist in the
      same population of neurons in the cortex, the present study investigated their
      colocalization in the rat medial prefrontal (MPC) and entorhinal (EC) cortices.
      Using antibodies that recognize epitopes specific to the serotonin 5-HT2A or 5
      HT1A receptors, studies employing confocal microscopy have shown that in the MPC
      5-HT2A receptors are preferentially, if not exclusively, present on the pyramidal
      neurons and that 5-HT1A-immunopositive material is present in the axonal hillocks
      and, to lower extend, in cytoplasm of presumably pyramidal cell bodies. With the
      regard of labeling of active receptors (i.e. present in shafts and axonal
      hillocks) we found that about 38% of neurons positive for the presence of
      serotonin 5-HT2A receptors, are also positive for serotonin 5-HT1A receptors in
      the MPC. In the EC, only 22% of serotonin 5-HT2A-positive neurons were positive
      for serotonin 5-HT1A receptor-immunoreactivity. In the respect of cytoplasmatic
      serotonin 5-HT1A receptor-immunoreactivity (possibly inactive receptors), 65% and
      73% of serotonin 5-HT2A receptor-positive neurons were colocalized with serotonin
      5-HT1A receptors in the MPC and EC, respectively. Data obtained on serotonin 5
      HT2A and 5-HT1A receptor localization provide anatomical grounds for at least
      three distinct populations of pyramidal neurons, one governed only by 5-HT2A, one
      only by 5-HT1A and one by both types of serotonin receptors.

PMID- 18622043
TI  - Abrogation of mitochondrial transcription in smooth muscle cells impairs smooth
      muscle contractility and vascular tone.
AB  - BACKGROUND: Smooth muscle cells (SMC) constitute the major contractile cell
      population of blood vessels and inner organs. SMC contraction depends on energy
      provided by adenosine triphosphate (ATP) catabolism, which can be generated
      through oxidative phosphorylation in mitochondria or by anaerobic glycolysis.
      Mitochondrial activity may also modulate smooth muscle tone by biotransformation
      of vasoactive mediators. Here, we study the role of mitochondrial DNA gene
      expression for vascular function in vivo. METHODS: Since loss of functional
      mitochondria in SMC may not be compatible with normal development, we generated
      mice with inducible SMC-specific abrogation of the mitochondrial transcription
      factor A (Tfam). Deletion of this gene leads to dysfunctional mitochondria and
      prevents aerobic ATP production in affected cells. RESULTS: Invasive blood
      pressure monitoring in live animals demonstrated that SMC specific Tfam deletion
      results in lower blood pressure and a defective blood-pressure response to
      stress, changes that were not compensated by increased heart rate. The
      contractility to agonists was reduced in arterial and gastric fundus strips from
      Tfam-deficient mice. Endothelium-dependent relaxation of arterial strips in
      response to ACh was also blunted. CONCLUSION: Our data show that mitochondrial
      function is needed for normal gastric contraction, vascular tone, and maintenance
      of normal blood pressure.

PMID- 18622044
TI  - Thyroid hormone receptor alpha 1: a switch to cardiac cell "metamorphosis"?
AB  - Thyroid hormone receptor alpha1 (TRalpha1) is predominantly expressed in the
      myocardium but its biological function under physiological or pathological
      conditions remains largely unknown. The present study investigated possible
      interactions between alpha1 adrenergic and thyroid hormone signaling at the level
      of TRalpha1, potential underlying mechanisms and physiological consequences, as
      well as the role of TRalpha1 in cell differentiation. This may be of
      physiological relevance since both thyroid hormone and adrenergic signalling are
      implicated in the pathophysiology of cardiac remodelling. Neonatal cardiomyocytes
      obtained from newborn rats (2-3 days) were exposed to phenylephrine (PE, an
      alpha1 adrenergic agonist) for 5 days, in the absence or excess of T3 in the
      culture medium. PE, in the absence of T3, resulted in 5.0 fold increase in
      TRalpha1 expression in nucleus and 2.0 fold decrease in TRalpha1 expression in
      cytosol, P<0.05. As a result, a fetal pattern of myosin isoform expression with
      marked expression of beta-MHC was observed in PE treated vs the untreated cells,
      P<0.05. PD98059 (an ERK signalling inhibitor) abrogated this response. In the
      presence of T3 in the culture medium, TRalpha1 expression was increased 1.6 fold
      in nucleus and 2.0 fold in cytosol in PE-T3 vs PE treated cells, P<0.05, and the
      fetal pattern of myosin isoform expression was prevented. Parallel studies with
      H9c2 myoblasts showed that reduction of T3 binding to TRalpha1 receptor delayed
      cardiac myoblasts differentiation without affecting proliferation. In conclusion,
      in neonatal cardiomyocytes, nuclear TRalpha1 is overexpressed after prolonged
      activation of the alpha1- adrenergic signalling by PE. This response seems to be
      an ERK kinase dependent process. Over-expression of TRalpha1 may lead to fetal
      cardiac phenotype in the absence of thyroid hormone availability. Furthermore,
      TRalpha1 seems to be critical in cardiac myoblast differentiation.

PMID- 18622046
TI  - The effect of sarcoplasmic reticulum Ca2+ leak on contractile activity of guinea
      pig heart myocytes depends in activity of sarcoplasmic reticulum Ca2+-ATPase and
      Na+/Ca2+ exchanger.
AB  - Decreased expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA),
      overexpression of Na(+)/Ca(2+) exchanger (NCX) and diastolic SR Ca(2+) leak from
      the ryanodine receptors (RyRs) are believed to contribute to the decrease of
      myocyte contraction in failing heart. In this work we induced Ca(2+) leak through
      RyRs in isolated myocytes of guinea pig hearts by 20 microM FK-506. The SR Ca(2+)
      leak resulted in (1) decreased amplitude of cell shortening and of Ca(2+)
      transients, (2) decreased rate of Ca(2+) transients decay (3) enhanced diastolic
      Ca(2+) loss. The effect of FK-506 on amplitude of cell shortening was reversed
      and that on diastolic Ca(2+) loss blocked by partial inhibition of NCX due to
      lowering Na(+) concentration in superfusion solution from 144 mM to 100 mM. The
      amplitude of cell shortening and Ca(2+) transients decreased by FK-506 was
      significantly increased by 10(-7) M thapsigargin. In conclusion, the effect of SR
      Ca(2+) leak induced by FK-506 on myocyte contraction is strictly dependent on
      activity of SERCA and NCX.

PMID- 18622045
TI  - Thyroid hormones suppress epsilon-PKC signalling, down-regulate connexin-43 and
      increase lethal arrhythmia susceptibility in non-diabetic and diabetic rat
      hearts.
AB  - We examined whether thyroid hormones affect myocardial epsilon-PKC signalling,
      downstream target substrate, connexin-43 (Cx43) and arrhythmogenesis in non
      diabetic and diabetic rats. Diabetes was induced by a single streptozotocin
      injection (50mg/kg, i.v.). Triiodothyronine (T(3)) was applied by gavage
      (1microg/kg of body weight for 10 days) to 4 weeks and 9 weeks diabetic and age
      matched non-diabetic rats. Western blot analysis of Cx43 and epsilon-PKC,
      immunofluorescence of Cx43, ultrastructure of cardiomyocytes and myocardial
      conduction velocity were performed. Isolated perfused heart preparation was used
      to test ventricular fibrillation susceptibility. T(3) significantly decreased
      epsilon-PKC expression in non-diabetic and suppressed in diabetic rat heart
      ventricles. Decline of epsilon-PKC signalling was associated with decrease of
      Cx43 phosphorylation in diabetic and to a greater extent in non-diabetic rat
      hearts. However, conduction velocity was significantly decreased in diabetic
      while enhanced due to T(3) and increased in non-diabetic T(3)-treated rat heart
      ventricles compared to non-treated. T(3)-induced down-regulation of Cx43 was
      associated with increased cardiac propensity to ventricular fibrillation.
      Findings indicate that activation of epsilon-PKC signalling linked with
      phosphorylation of Cx43 is one of the mechanisms involved in the adaptation of
      the heart to hyperglycemia. Suppression of epsilon-PKC and Cx43 phosphorylation
      by T(3) abolish benefit of adaptation rendering the heart prone to lethal
      arrhythmias.

PMID- 18622047
TI  - Src kinase-mediated parallel activation of prostaglandin and constitutive nitric
      oxide synthase pathways in leptin protection of gastric mucosa against ethanol
      cytotoxicity.
AB  - Advances in understanding the functional aspects of leptin in the processes
      affecting peripheral tissues have brought to the forefront the role of this
      pluripotent cytokine in the processes of gastric mucosal defense and repair.
      Here, we report that leptin protects the gastric mucosal cells against ethanol
      cytotoxicity. We show that ethanol cytotoxicity, characterized by a marked drop
      in the mucosal cells capacity for NO production, arachidonic acid release and
      prostaglandin generation, was subject to suppression by leptin. The loss in
      countering capacity of leptin on the ethanol-induced cytotoxicity was attained
      with cyclooxygenase inhibitor, indomethacin and nitric oxide synthase (cNOS)
      inhibitor, L-NAME, as well as PP2, an inhibitor of Src kinase. Indomethacin
      caused the inhibition in PGE(2) generation, pretreatment with L-NAME led to the
      inhibition in NO production, whereas PP2 exerted the inhibitory effect on leptin
      induced changes in NO, arachidonic acid and PGE(2). The leptin-induced changes in
      arachidonic acid release and PGE(2) generation were blocked by ERK inhibitor,
      PD98059, but not by PI3K inhibitor, wortmannin. Moreover, the stimulatory effect
      of leptin on the mucosal cells cNOS activity was inhibited not only by PP2, but
      also by Akt inhibitor, SH-5. Our findings demonstrate that leptin protection of
      gastric mucosa against ethanol cytotoxicity involves Src kinase-mediated
      bifurcated activation of MAPK/ERK and Akt that leads to up-regulation of the
      respective prostaglandin and nitric oxide synthase pathways.

PMID- 18622048
TI  - Roles of nitric oxide (NO) and NO synthases in healing of dextran sulfate sodium
      induced rat colitis.
AB  - We examined the effects of various NO inhibitors on the healing of DSS-induced
      rat colitis. Experimental colitis was induced by feeding rats for 6 days with
      2.5% DSS in drinking water. After DSS treatment, the animals were fed normally
      and killed various days up to 7 days later. L-NAME (a nonselective NOS inhibitor)
      or aminoguanidine (a selective iNOS inhibitor) was given p.o. twice daily for 6
      days starting from the termination of DSS treatment. The area of lesions, colon
      length and MPO activity were measured on day 7 after DSS treatment. DSS treatment
      caused severe lesions in the colon, accompanied by an increase in MPO activity
      and a decrease in colon length. The lesions healed gradually after
      discontinuation of DSS treatment, with a histological restoration and subsidence
      of inflammation. The healing of DSS-induced colonic lesions was significantly
      impaired by daily administration of L-NAME or aminoguanidine, the effects being
      all but equivalent between these drugs, and the effect of L-NAME was
      significantly reverted by the co-administration of L-arginine. The expression of
      nNOS protein was observed in the colonic mucosa with or without DSS treatment,
      while those of iNOS and eNOS were markedly upregulated after DSS treatment.
      Likewise, the expression of VEGF was also up-regulated in the colon following DSS
      treatment, and this response was suppressed by both L-NAME and aminoguanidine.
      These results suggest that endogenous NO produced by mainly iNOS and partly eNOS
      contributes to the healing of DSS-induced colonic lesions, through the
      upregulation of VEGF expression and enhancement of angiogenesis.

PMID- 18622049
TI  - Ischemic preconditioning of the hindlimb or kidney does not attenuate the
      severity of acute ischemia/reperfusion-induced pancreatitis in rats.
AB  - Ischemic preconditioning of several organs, including the pancreas has been shown
      to protect these organs from injury evoked by subsequent exposure to severe
      ischemia followed by reperfusion. Moreover, it has been shown that ischemic
      preconditioning of distant organs such as the kidney, intestine or limb may
      protect the heart as effectively as cardiac preconditioning itself. This study
      was designed to determine whether ischemic preconditioning of the kidney or
      hindlimb protects the pancreas against ischemia/reperfusion-induced pancreatitis.
      METHODS: In male Wistar rats, remote ischemic preconditioning of the pancreas was
      performed by clamping of right femoral or renal artery twice for 5 min with 5 min
      interval. Direct ischemic preconditioning was performed by clamping of celiac
      artery. Thirty min after ischemic preconditioning or sham-operation, acute
      pancreatitis was induced by clamping of inferior splenic artery for 30 min
      followed by reperfusion. After 6, 12 h or 1, 2, 3, 5 or 9 days of reperfusion the
      experiment was ended. Secretory studies were performed 2 h after exposure to
      direct or remote ischemic preconditioning of the pancreas in conscious rats with
      chronic pancreatic fistula. RESULTS: Direct ischemic preconditioning of the
      pancreas applied alone reduced pancreatic exocrine secretion; whereas ischemic
      preconditioning of the hindlimb or kidney was without effect on pancreatic
      secretion. Direct ischemic preconditioning of the pancreas attenuated the
      severity of acute pancreatitis. It was found as a reduction in the pancreatitis
      evoked increase in serum activity of lipase and amylase, a decrease in serum
      concentration of pro-inflammatory interleukin-1beta, diminution of histological
      signs of pancreatic damage, as well as, an improvement of pancreatic blood flow
      and DNA synthesis. Remote ischemic preconditioning of the pancreas evoked by
      short-lasting ischemia of the hindlimb or kidney was without any protective
      effect in ischemia/reperfusion-induced pancreatitis. Moreover, this procedure led
      to a significant increase in serum activity of lipase and amylase, and enhanced
      the morphological signs of pancreatic damage. CONCLUSION: In contrast to direct
      ischemic preconditioning, remote ischemic preconditioning of the pancreas is
      without effect on pancreatic exocrine secretion and does not reduce the severity
      of ischemia/reperfusion-induced pancreatitis.

PMID- 18622050
TI  - Division of motor units into fast and slow of the basis of profile of 20 Hz
      unfused tetanus.
AB  - In the medial gastrocnemius muscle of intact rats, division of motor units (MUs)
      into slow (S) or fast (F) types is typically based on presence of a sag
      phenomenon in 40 Hz unfused tetanic contraction. MUs with sag are classified as
      F, while those without sag as S. However, in rats one month after spinal cord
      injury this phenomenon almost completely disappears and cannot be used as a basis
      for MUs differentiation, whereas the twitch contraction time increased
      significantly. Analysis of myosin heavy chain (MHC) isoform composition confirmed
      transformational changes of muscle fibres after spinal cord transection and
      indicated unchanged proportion of type I MHC isoforms, disappearance of type IIa
      MHC isoforms, and increase of type IIb MHC isoforms. We proposed an additional
      method for division of MUs into types when standard criteria are not applicable.
      It was observed that relative effectiveness of force summation during 20 Hz
      tetanus, described as a ratio of the force of the last contraction of this
      tetanus to the force of the first contraction, did not change after spinal cord
      injury. This ratio for S MUs both in intact and spinal rats exceeded 2.0, whereas
      for F units was lower than 2.0. Calculations of this ratio made for better fused
      tetani, evoked by 30 Hz or 40 Hz stimulation, showed overlapping values. We
      conclude that this 20 Hz tetanus index appears to be an alternative method useful
      for division of motor units into S and F types.

PMID- 18622051
TI  - Nitric oxide in the adrenergic-and CRH-induced activation of hypothalamic
      pituitary-adrenal axis.
AB  - In this report we investigated the effect of 7-nitroindazole (7-NI), a specific
      neuronal inhibitor of nitric oxide synthase (nNOS) and L-NAME, a nonselective NOS
      inhibitor upon the adrenergic- and CRH-induced stimulation of the hypothalamic
      pituitary-adrenal axis in nonanesthetized rats. 7-NI given i.p. and L-NAME
      administered i.c.v. considerably reduced ACTH and corticosterone secretion
      induced by phenylephrine (30 microg i.c.v.), an alpha(1)-adrenergic receptor
      agonist. These inhibitors also diminished the HPA response to isoprenaline (20
      microg i.c.v.), a nonselective beta-adrenergic receptor agonist, and i.c.v. L
      NAME significantly lowered the ACTH and corticosterone response to clenbuterol
      (10 microg i.c.v.), a selective beta(2)-adrenergic agonist. L-NAME abolished the
      noradrenaline (NA), an alpha- and beta-receptor agonist-evoked ACTH and
      corticosterone response, which was reversed by pretreatment with i.p. L-arginine,
      an endogenous NO substrate. 7-NI abolished the stimulatory action of
      corticotropin-releasing hormone (CRH 1 microg/kg i.p.) on ACTH but not
      corticosterone secretion. L-NAME only moderately diminished the CRH-induced ACTH
      secretion, suggesting that a major part of the CRH-induced HPA axis activation is
      of neuronal origin. Dihydropyridine, nifedipine, a specific L-type Ca(2+) channel
      blocker, inhibited significantly the CRH-induced ACTH and corticosterone response
      in rats exposed to 3 days crowding stress but not in rats under basal conditions.
      This finding indicates the strategic importance of Ca(2+) influx into the
      pituitary corticotrops to meet increased secretory requirement under stressful
      conditions. Collectively, our results point to complex functional relationship
      between NO, adrenergic agents CRH and Ca(2+) in the regulation of HPA axis
      activity.

PMID- 18622052
TI  - Beneficial effect of alpha-lipoic acid on lipopolysaccharide-induced oxidative
      stress in bronchoalveolar lavage fluid.
AB  - Lipopolysaccharide (LPS) from gram-negative bacteria is a major factor that
      contributes to multiple organ failure including lung injury. Among LPS-induced
      metabolites, reactive oxygen species are considered to play a crucial pathogenic
      role in the lung damage. In this study, the effect of early administration of an
      antioxidant, alpha-lipoic acid (LA), on bronchoalveoar lavage fluid (BALF) lipid
      peroxidation, hydrogen peroxide (H(2)O(2)), sulphydryl group (-SH) concentration
      and total protein concentration was evaluated in rats with endotoxic shock
      induced by administration of LPS (Escherichia coli 026:B6, 30 mg/kg, i.v.). The
      animals were treated intravenously with normal saline or LA (60 mg/kg or 100
      mg/kg i.v.) 30 min after LPS injection. Five hours after LPS or saline
      administration, the animals were sacrificed and BALF was obtained for
      measurements. The results showed that the levels of oxidative markers,
      thiobarbituric acid reactive substances (TBARS) and H(2)O(2) were increased
      significantly in BALF, whereas they were decreased significantly on treatment
      with LA. The concentrations of -SH groups were significantly increased and total
      protein concentration was insignificantly decreased in the LPS/LA group. There
      was no difference in oxidative stress reduction between 60 mg/kg and 100 mg/kg
      doses. These results indicate that early administration of lipoic acid provides
      protective effects against endotoxin-induced oxidative stress in the lung and
      supports the idea that alpha-lipoic acid is a free radical scavenger and a potent
      antioxidant.

PMID- 18622053
TI  - Kaempferol, but not resveratrol inhibits angiotensin converting enzyme.
AB  - Inhibition of angiotensin converting enzyme (ACE) has proved to be beneficial in
      the treatment of various cardiovascular disorders. The aim of this study was to
      evaluate ACE inhibitory potential of two polyphenolic compounds with different
      structures: resveratrol (present in high quantities in French wine) and
      kaempferol (abundant in greens), using method of liquid chromatography coupled
      with electrospray ionization mass spectrometry (LC-ESI-MS) for ex vivo
      measurement of angiotensin I to angiotensin II conversion by ACE in aortic tissue
      of Wistar-Kyoto rats. In this setting, kaempferol (10-30-100 microM), but not
      resveratrol (10-30-100 microM) appeared to inhibit dose-dependently conversion of
      Ang I to Ang II. Although the mechanism of ACE inhibition by kaempferol remains
      to be elucidated, this observation may help in search or designing of new classes
      of ACE inhibitors.

PMID- 18622054
TI  - Modulation of microglia can attenuate neuropathic pain symptoms and enhance
      morphine effectiveness.
AB  - Microglia play a crucial role in the maintenance of neuronal homeostasis in the
      central nervous system, and microglia production of immune factors is believed to
      play an important role in nociceptive transmission. There is increasing evidence
      that uncontrolled activation of microglial cells under neuropathic pain
      conditions induces the release of proinflammatory cytokines (interleukin - IL
      1beta, IL-6, tumor necrosis factor - TNF-alpha), complement components (C1q, C3,
      C4, C5, C5a) and other substances that facilitate pain transmission.
      Additionally, microglia activation can lead to altered activity of opioid systems
      and neuropathic pain is characterized by resistance to morphine. Pharmacological
      attenuation of glial activation represents a novel approach for controlling
      neuropathic pain. It has been found that propentofylline, pentoxifylline,
      fluorocitrate and minocycline decrease microglial activation and inhibit
      proinflammatory cytokines, thereby suppressing the development of neuropathic
      pain. The results of many studies support the idea that modulation of glial and
      neuroimmune activation may be a potential therapeutic mechanism for enhancement
      of morphine analgesia. Researchers and pharmacological companies have embarked on
      a new approach to the control of microglial activity, which is to search for
      substances that activate anti-inflammatory cytokines like IL-10. IL-10 is very
      interesting since it reduces allodynia and hyperalgesia by suppressing the
      production and activity of TNF-alpha, IL-1beta and IL-6. Some glial inhibitors,
      which are safe and clinically well tolerated, are potential useful agents for
      treatment of neuropathic pain and for the prevention of tolerance to morphine
      analgesia. Targeting glial activation is a clinically promising method for
      treatment of neuropathic pain.

PMID- 18622055
TI  - Glyburide for the treatment of gestational diabetes mellitus.
AB  - Insulin is the traditional treatment for gestational diabetes mellitus (GDM)
      unresponsive to dietary interventions. Until recently, oral hypoglycemic drugs
      had been contraindicated due to concerns regarding teratogenicity and the
      possibility of neonatal hypoglycemia. In contrast to other sulfonylurea drugs, in
      vitro and in vivo investigations have demonstrated very low transplacental
      transport of glyburide to the fetal circulation. The mechanisms preventing
      glyburide from crossing the human placenta are not completely understood. A
      combination of extremely high protein binding and a relatively short elimination
      half-life might partially explain it. It has also been demonstrated that
      glyburide is effluxed from the fetal to the maternal circulation by the breast
      cancer resistance protein (BRCP) and the human multidrug resistance protein 3
      (MRP3). Since 2000, several studies have reported an 80-85% success rate of
      glyburide treatment. However, some authors have noticed glyburide-related
      increased risk of preeclampsia, macrosomia, neonatal hypoglycemia, admission to a
      neonatal intensive care unit and need for phototherapy. These possible maternal
      as well as neonatal adverse outcomes warrant further investigations. Until that
      time, the use of glyburide should remain inadvisable in pregnancy.

PMID- 18622056
TI  - Paradoxical effects of adenosine receptor ligands on hydroxyl radical generation
      by L-DOPA in the rat striatum.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder associated
      with selective loss of dopaminergic neurons in substantia nigra pars compacta.
      Among the proposed mechanisms of dopaminergic degeneration, oxidative stress is
      believed to play an important role. On the other hand, L-DOPA used as the main
      medication in PD and overproduction of dopamine (DA) in striatal neurons could
      elicit toxic effects due to formation of free radicals (FRs). Adenosine, an
      endogenous neuromodulator was shown in various experimental models to have
      neuroprotective properties. In our study, we investigated the role of adenosine
      A(1) and A(2A) receptor ligands in hydroxyl radical generation by L-DOPA in the
      rat striatum. The hydroxyl radical was assayed by HPLC-ED as a product of its
      reaction with p-hydroxybenzoic acid (PBA). Intrastriatal infusion of L-DOPA(50
      microM) markedly increased dialysate level of DA and 3,4-dihydroxybenzoic acid
      (3,4-DHBA). An adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA, 25
      50 microM), nonselectiveA(1)/A(2A) receptor agonist 2-chloroadenosine (2-CADO, 50
      100 microM), and selective A(2A) receptor agonist CGS 21680 (25-50 microM)
      decreased the level of 3,4-DHBA. A non-selective A(1)/A(2A) adenosine receptor
      antagonist caffeine (100 microM) produced similar effect on 3,4-DHBA level. At
      the same time, CPA and 2-CADO, but not CGS 21680 or caffeine, decreased L-DOPA
      induced DA release. The adenosine receptor ligands alone only weakly changed
      extracellular DA level and did not influence hydroxyl radical production.
      However, they showed scavenging activity in Fenton reaction in vitro. The primary
      caffeine metabolite in rodents, 1,3,7-trimethyl uric acid (1,3,7-mUA) decreased
      both, DA synthesis and 3,4-DHBA level. Thus, paradoxically, both agonists of A(1)
      receptor and agonist of A(2A) receptor as well as antagonist of A(1) and A(2A)
      receptors (caffeine), all decreased generation of FRs. Our study suggests that a
      decrease in hydroxyl radical generation caused by adenosine receptor ligands
      results from attenuation of L-DOPA-induced DA release or from their scavenging
      activity.

PMID- 18622057
TI  - Neonatal N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) treatment modifies
      the vulnerability to phenobarbital- and ethanol-evoked sedative-hypnotic effects
      in adult rats.
AB  - To study the influence of the central noradrenergic system on sensitivity to
      sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact
      rats were contrasted with rats in which noradrenergic nerves were largely
      destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N
      ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the
      righting reflex (LORR) was used as an index to study the acute sedative-hypnotic
      effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v).
      Additionally, GABA concentration in the medial prefrontal cortex (PFC),
      hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method.
      Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both
      phenobarbital and ethanol in adult rats. While the endogenous GABA content in the
      PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered,
      phenobarbital significantly decreased GABA content of both intact and DSP-4
      lesioned rats by approximately 40% in the hippocampus and by approximately 20% in
      other brain regions at 1 h. Ethanol reduced GABA content by approximately 15-30%
      but only in the hippocampus and brainstem of both intact and lesioned rats. These
      findings indicate that the noradrenergic system exerts a prominent influence on
      sedative-hypnotics acting via GABAergic systems in the brain without directly
      altering GABA levels in the brain.

PMID- 18622058
TI  - Antinociceptive activity of sildenafil and adrenergic agents in the writhing test
      in mice.
AB  - The authors investigated the antinociceptive activity of sildenafil and
      adrenergic agents co-administered in the writhing test in mice. The intensity of
      nociception was quantified by the number of writhes occurring between 0 and 30
      min after stimulus injection. Nontreated groups (NT) received acid
      intraperitoneally (ip) followed by sterile saline (ip). Animals received (ip)
      sildenafil (2.5 or 5 mg/kg), propranolol (0.5 or 2 mg/kg), atenolol (0.05 or 2
      mg/kg), prazosin (0.05 or 0.25 mg/kg) or clonidine (0.01 or 0.1 mg/kg) 30 min
      before acid injection. It was observed that only the largest doses of every drug
      inhibited the number of writhes in mice. In another series of experiments,
      animals were pretreated with the lower ineffective doses of propranolol,
      atenolol, prazosin or clonidine. After 30 min, mice also received the lower
      ineffective dose of sildenafil followed by acid injection. The combination of
      ineffective doses of propranolol, atenolol, prazosin or clonidine with sildenafil
      significantly inhibited the nociceptive response induced by acetic acid
      injection. Data obtained from these experiments showed that ineffective doses of
      sildenafil associated with ineffective doses of adrenergic agents provided
      analgesic effects in the writhing test.

PMID- 18622059
TI  - Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis.
AB  - We investigated the influence of recurrent epileptic seizures on the arachidonic
      acid (AA) cascade in platelets and brain microvessels, using [(14)C]AA as a
      tracer substrate and chromatographic determination. The recurrent epileptic
      seizures of male Wistar rats were induced every second day with 3-aminopyridine
      (3-AP, 25 mg/kg ip) for two weeks. In the chronic 3-AP model, the earlier
      epileptic insults resulted in a decreased incidence of limbic seizures and higher
      survival rate at later administration of 3-AP. After 3-AP treatment, the
      formation of lipoxygenase products was unchanged, but the total amount of
      cyclooxygenase (COX) metabolites was decreased both in platelets and brain
      microvessels. The reduction in COX-mediated eicosanoid synthesis after recurrent
      seizures was due to the decreased synthesis of vasodilator and vasoconstrictor
      COX metabolites. In platelets, the 3-AP-treatment reduced the synthesis of
      vasodilator prostacyclin (PGI(2)), prostaglandin E(2) (PGE(2)) and 12-L-hydroxy
      5,8,10-heptadecatrienoic acid (12-HHT), while the synthesis of prostaglandin D(2)
      (PGD(2)) remained unchanged. In isolated brain capillaries, the PGD(2), PGE(2)
      and 12-HHT synthesis was decreased after recurrent seizures. As for the
      vasoconstrictor COX metabolites, both platelets and brain microvessels
      synthesized significantly lesser amount of prostaglandin F(2alpha) (PGF(2alpha))
      and thromboxane A(2) (TxA(2)) upon 3-AP administration. Our results indicate that
      platelets and isolated brain capillaries synthesize significantly lesser amount
      of COX metabolites after chronic 3-AP treatment. The decreased conversion of AA
      into different COX products may play a role in the neuroprotective/preconditional
      adaptation of the brain against subsequent seizures.

PMID- 18622060
TI  - Effect of the pyridoindole SMe1EC2 and compounds affecting A(1) and A(2A)
      adenosine receptors in rat hippocampus under ischemia in vitro.
AB  - The effect of the newly synthesized pyridoindole antioxidant SMe1EC2 (1
      micromol/l) and drugs activating or inhibiting adenosine receptors was tested
      under ischemia. Synaptic transmission was recorded extracellularly before and
      under 6-min ischemia and 20-min reoxygenation in rat hippocampal slices in vitro.
      In untreated slices, ischemia elicited failure of synaptic transmission and
      excitability expressed by a population spike decay (t(0.5) = 1.7 +/- 0.1 min) and
      poor recovery of synaptic transmission at the end of reoxygenation, expressed as
      percentage of PoS amplitude of that at zero minute of ischemia (9.9 +/- 3.6%).
      The compound SMe1EC2 increased recovery of PoS amplitude in reoxygenation (31.2
      +/- 7.0% of that at the beginning of ischemia) and decreased the number of
      irreversibly damaged slices in reoxygenation (64%) compared to untreated slices
      (80%). Co-administration of SMe1EC2 + SCH-58261 (1 micromol/l, A(2A) adenosine
      receptor antagonist) resulted in delayed synaptic transmission decay during 6-min
      ischemia (t(0.5) = 2.3 +/- 0.1 min), increased PoS amplitude recovery during
      reoxygenation (37.7 +/- 12.4% of that at zero minute of ischemia), and in a
      decreased number of slices with damaged synaptic transmission at the end of
      reoxygenation (54%), all data compared to untreated controls. Co-administration
      of pyridoindole with CGS 21680 (1 micromol/l, A(2A) adenosine receptor agonist)
      or with DPCPX (100 nmol/l, A(1) adenosine receptor antagonist) eliminated the
      described effect. Further studies are required to elucidate the putative
      influence of manipulation with adenosine receptors on the neuroprotective effect
      of SMe1EC2 under ischemia.

PMID- 18622061
TI  - Can we use adenosine diphosphate (ADP) to study "aspirin resistance"? The Janus
      faces of ADP-triggered platelet aggregation.
AB  - There is a growing number of contradictory reports indicating that adenosine
      diphosphate (ADP) can be a useful agonist in monitoring of the antiplatelet
      action of acetylsalicylic acid (ASA) in humans and animals. In the current study,
      we aimed to determine the conditions for using ADP to trigger platelet
      aggregation in order to detect ASA-mediated inhibition of rat platelet
      reactivity. Initially, we examined the usefulness of different ADP concentrations
      (0.25, 0.5, 1, 5 and 10 microM) in detecting the in vitro ASA mediated platelet
      inhibition using whole blood aggregometry, as well as we monitored the role of
      ADP in generation of thromboxane A(2) (TXA(2)). To study ex vivo ASA inhibitory
      potential on platelet aggregation induced by a range of ADP concentrations,
      animals were subjected to one or 10-day ASA administration at the dose of 50
      mg/kg. Our experiment shows that ADP in a concentration-dependent manner induces
      TXA(2) generation in the whole blood with hirudin as an anticoagulant. However,
      in vitro and ex vivo examination of ASA inhibitory potential on platelet
      aggregation revealed that irrespectively of administration regimen, ASA failed to
      block platelet aggregation induced by ADP at the concentrations higher than 0.5
      microM. Our findings suggest that the mechanism of ADP-induced platelet
      aggregation depends on agonist concentration. It appears that only low ADP
      concentrations (up to 0.5 microM) induce TXA(2)-dependent rat platelet
      aggregation. Therefore, ADP could be considered a useful platelet agonist for
      monitoring of ASA-mediated platelet inhibition only if used at much lower
      concentrations than those commonly employed.

PMID- 18622062
TI  - Comparison of cardioprotective effects of salvianolic acid B and benazepril on
      large myocardial infarction in rats.
AB  - In the present study, we compared cardioprotective effects of salvianolic acid B
      (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats
      with large myocardial infarction (MI). The large MI was produced by coronary
      artery ligation for 4 weeks in rats. The rats were divided into the following
      groups: sham operation; MI; MI + Sal B (100 mg/kg by a gavage, once a day for 4
      weeks) and MI + benazepril (1 mg/kg by a gavage, once a day for 4 weeks).
      Echocardiogram, hemodynamic and hemorheological changes, angiogenesis, infarct
      size and cardiac remodeling, as well as messenger ribonucleic acid (mRNA) of
      vascular endothelium growth factor (VEGF) were measured. The following similar
      effects were observed in MI rats treated with Sal B and benazepril: (1) a marked
      improvement of echocardiographic, hemodynamic and hemorheological parameters, (2)
      significant reduction of infarct size, (3) significantly attenuated heart
      hypertrophy, left ventricular (LV) dilatation and fibrosis. The unique effects of
      Sal B were: angiogenesis and augmented VEGF expression in the border and remote
      noninfarcted LV area. These results suggest that Sal B and benazepril exerted
      beneficial cardioprotective effects. However, Sal B enforced some different
      modality than benazepril, which might improve myocardial microcirculation by
      augmenting VEGF expression and promoting angiogenesis besides similar effects to
      benazepril.

PMID- 18622063
TI  - Protective effects of telmisartan against acute doxorubicin-induced
      cardiotoxicity in rats.
AB  - The therapeutic usefulness of doxorubicin (DXR), an anthracycline antibiotic, is
      limited by its cardiotoxicity. The present study investigated the effects of
      telmisartan, an angiotensin II receptor (AT1) antagonist against doxorubicin
      induced cardiotoxicity in rats using biochemical and histopathological
      approaches. Doxorubicin (20 mg/kg) was injected intraperitoneally (ip) as a
      single dose and telmisartan (10 mg/kg) was administered orally for 7 days. Rats
      treated with DXR showed cardiotoxicity as evidenced by elevation of serum lactate
      dehydrogenase (LDH) activity, tissue malondialdehyde (MDA) level, catalase
      activity and a decrease in the level of glutathione (GSH). Pre- and post
      treatment with telmisartan elicited a significant decrease in the activities of
      LDH and catalase in comparison with DXR-treated group. Furthermore, pretreatment
      with telmisartan also decreased lipid peroxidation (MDA level) and increased the
      GSH content in comparison with DXR group. However, the difference in lipid
      peroxidation and GSH content were not statistically significant in post-treated
      group. Histopathological studies showed disruption of cardiac tisuues in DXR
      groups. Pre- and post-treatment with telmisartan reduced the damage of cardiac
      tissue in rats. These results suggest that telmisartan treatment provides a
      significant protective effect against acute-doxorubicin induced cardiotoxicity in
      rats.

PMID- 18622064
TI  - Yohimbine-induced alterations in alpha(2)-adrenoceptors in kidney regions of the
      spontaneously hypertensive rats: an autoradiographic analysis.
AB  - We have tested the hypothesis that a pharmacologically determined alteration in
      renal alpha(2)-adrenoceptor (alpha(2)-AR) density might be a pathophysiologically
      important factor of genetic hypertension in the spontaneously hypertensive rats
      (SHRs). First, we compared he regional distribution and biochemical parameters of
      alpha(2)-ARs in SHRs and Wistar-Kyoto (WKY) rats, using the full agonist [(3)H]UK
      14304. Secondly, we evaluated the effect of selective blockade and stimulation of
      alpha(2)-ARs on the development of hypertension and on renal alpha(2)-AR density
      and regional distribution in SHRs. [(3)H]UK 14304 binding was distributed
      predominantly over the outer medulla, less abundantly over the inner medulla and
      was almost absent from the renal cortex. Renal alpha(2)-ARs were found to be
      increased in SHRs at the ages tested compared with their respective controls and
      the increase was completely localized to the outer medulla. In these rats, blood
      pressures immediately before sacrifice were significantly higher in the
      hypertensive group compared with normotensive controls. The daily administration
      of SK&F 86,466 or clonidine significantly decreased the blood pressure but the
      autoradiographic studies showed that the prolonged administration of yohimbine to
      rats for two weeks resulted in a large increase in the density of alpha(2)-ARs in
      some areas of the rat kidney but not in others. Taken together these data do not
      support the hypothesis that alteration in renal alpha(2)-ARs (as measured by
      autoradiography) is crucial for the maintenance of hypertension in the SHR model.

PMID- 18622065
TI  - Effect of luteinizing hormone-releasing hormone (LHRH) analogue treatment on a
      cytokine profile in prostate cancer patients.
AB  - The aim of the study was to test serum concentrations of the chosen cytokines in
      patients with prostate cancer (PCa) treated with an luteinizing hormone-releasing
      hormone (LHRH) analogue. We tested interleukin (IL)-2, IL-10, tumor necrosis
      factor (TNF)-alpha, interferon (INF)-gamma in blood at three time points; I -
      before the injection, II - 10 days and III - 20 days after the injection in 14
      men with PCa. Patients had one depot injection of the LHRH analogue monthly. The
      cytokine concentrations in serum samples were determined by ELISA method.
      Prostate specific antigen (PSA) level was examined before and after six months of
      the LHRH analogue treatment. After six months of the therapy, we observed
      normalization of serum PSA value from 16.48 ng/ml to 1.45 ng/ml. LHRH analogue
      injection resulted in a significant drop of the IL-2 concentration, and the value
      gradually returned to normal in the next 20 days. IL-10 concentration transiently
      increased and then was down-regulated. Serum TNF-alpha and INF-gamma
      concentrations in PCa patients were significantly lower compared to controls and
      were not affected by the treatment. LHRH analogue treatment in PCa patients
      modulates concentrations of the chosen cytokines which may result both in
      antitumor and a transient immunosuppressive effect.

PMID- 18622066
TI  - Trans-species assessment of antidepressant activity in a rodent model of
      depression.
AB  - Olfactory bulbectomy (OB), a preclinical model of depression, has most often been
      performed and validated in rats, but not as comprehensively in other rodent
      species. This study demonstrated that bulbectomy induced a hyperactive response
      in the open field test in three rodent species, namely the rat, mouse and
      hamster. OB, in all species, produced an increase in the distance travelled in
      the perimeter of the arena. The OB mouse was the only species to demonstrate
      increased distance travelled in the central part of the arena. These behavioral
      disturbances were attenuated in all species following chronic treatment with the
      antidepressant imipramine.

PMID- 18622067
TI  - Dose-response relationship analysis of vigabatrin doses and their antinociceptive
      effects in the hot-plate test in mice.
AB  - This study was aimed at determining the analgesic effects of vigabatrin (VGB, a
      newer antiepileptic drug) in the acute thermal pain model (hot-plate test) in
      mice. Linear regression analysis was used to evaluate a dose-response
      relationship between logarithms of VGB doses and their resultant maximum possible
      antinociceptive effects (MPAE) in the hot-plate test in mice. From the linear
      equation of dose-response relationship, doses of VGB that increased the
      antinociceptive effect by 15%, 20% and 25% were calculated and amounted in this
      study to 144, 383 and 1,016 mg/kg, respectively. In conclusion, VGB in a dose
      dependent manner produces the analgesic effects in mice in the hot-plate test.
      The method allowing for the calculation of doses of VGB increasing the
      antinociceptive effects by 15%, 20% and 25% can be readily adapted to preclinical
      studies because these values perfectly characterize the potency of antiepileptic
      drugs with respect to suppression of acute thermal pain in mice.

PMID- 18622069
TI  - The nature of plague in late eighteenth-century Egypt.
AB  - This article uses an examination of the 1791 plague in Egypt to explore the
      relationships among disease, famine, flood, drought, and death in late eighteenth
      century Egypt. It analyzes how plague functioned as part of a regular biophysical
      pathology of the environment in which the disease came and went as one iteration
      in a cycle that included famine, wind, flood, drought, price inflation, and
      revolt. Using the works of Egyptian chroniclers, archival materials, secondary
      studies, and traveler accounts, this article integrates plague into the study of
      the Egyptian environment by showing how it was a regular and expected part of
      life in Egypt.

PMID- 18622068
TI  - Comparison of the analgesic efficacy of preemptive and preventive tramadol after
      lumpectomy.
AB  - The aim of this study was to investigate the analgesic efficacy of tramadol
      administrated preemptively or preventively in the earlier period of lumpectomy.
      Four hundred American Society of Anesthesiologists (ASA) physical status I-II
      patients, undergoing lumpectomy, were screened and 317 were randomly assigned
      into one of two groups. In the preemptive tramadol (n = 158) group, patients
      received an iv injection of tramadol 100 mg 15 min before operation. The
      preventive group (n = 159) received the same dose of tramadol 15 min before the
      end of the operation. Pain intensity at rest, overall satisfaction score,
      morphine consumption and side effects were recorded. A total of 299 patients
      completed the study. Preemptive and preventive subjects experienced similar
      analgesic effect and feeling of satisfaction at the first 24 h after surgeries.
      The similar amount of additional morphine was consumed [4.6 mg (95% CI 1.5-7.2)
      vs. 4.1 mg (95% CI 1.2-6.3), p = 0.811]. No intergroup difference was observed in
      the incidence of side effects. In conclusion, preemptive and preventive
      administration of tramadol expressed analgesia of similar efficacy up to 24 h
      after lumpectomy. The additional morphine requirement, the overall satisfaction
      and the frequency of side effects all did not display significant difference
      between the two groups. This implies that the administration of tramadol either
      before the start or before the end of the surgical procedures all can produce
      effective postoperative analgesia.

PMID- 18622070
TI  - Sacagawea's "cold": pregnancy and the written record of the Lewis and Clark
      Expedition.
AB  - In June 1805, Sacagawea fell gravely ill along the Missouri River during the
      outward journey of the Corps of Discovery. Historical discussion of her illness
      has failed to take into account the context of travel literature and writing at
      the time-in particular, the conventions governing references to personal
      experience, descriptions of Native American life, and the language of women's
      bodies. When William Clark and Meriwether Lewis wrote in their journals that
      Sacagawea was dangerously ill because she had "taken a cold," and that they
      blamed her partner Toussaint Charbonneau for her illness, they likely meant that
      she was pregnant and had miscarried. Their references, obscure now, made sense
      under the conventions of writing at the time and in the context of intense
      medical interest in the relationship of cold to women's menstrual cycles.
      Deciphering this episode adds to our understanding of the often intimate
      relations on the Lewis and Clark Expedition and broadens the ramifications of the
      concept of "cold" in the context of women's health. Such an interpretation brings
      new insight to this crucial chapter in U.S. western history and sheds light on
      the productive ambiguity often employed in discussions of women's health.

PMID- 18622071
TI  - Doctors on record: Uruguay's infant mortality stagnation and its remedies, 1895
      1945.
AB  - Circa 1900 Uruguayan medical authorities prided themselves on their country's
      health achievement: the lowest recorded infant mortality rate in Latin America
      and one of the lowest rates in the world. Over the next three decades, however,
      these doctors' pride suffered blow after blow as Uruguay's infant mortality
      stagnated at roughly the same 1900 rate, while other countries experienced
      sustained mortality declines. Even more frustrating was the apparent inadequacy
      of the measures that physicians themselves had advocated and implemented. This
      paper explores Uruguay's infant mortality dynamics during the first half of the
      twentieth century through the observations, acerbic debates, analyses, policy
      making, and administrative perspectives of the country's pediatricians and public
      health experts. Only after infant health began to be addressed as an integral
      part of Uruguay's burgeoning welfare state in the 1930s did infant mortality
      rates start to decline once again.

PMID- 18622072
TI  - "Physicians are not bootleggers": the short, peculiar life of the Medicinal
      Alcohol Movement.
AB  - This essay seeks to chronicle the effort of physicians to secure the right to
      prescribe beer, liquor, and other alcoholic beverages to their patients for
      medicinal uses during the Prohibition era. A review of the medical literature and
      popular press from the period 1920-26 reveals that the physicians who lobbied for
      the right to prescribe alcohol and, ultimately, took their claim to the United
      States Supreme Court, were not uniformly antiprohibitionists attempting to
      circumvent the Eighteenth Amendment. Instead, this coalition of physician
      activists, led by John P. Davin and Samuel W. Lambert, included both supporters
      and opponents of prohibition. Their attitudes on the therapeutic value of beer
      and liquor also varied widely. Yet what united these men and women-and what
      defined their movement-was opposition to state interference with the practice of
      medicine and an increasing concern with the federal government's role in the
      regulation of their profession. The defeat of their efforts, presaging the
      passage of the Sheppard Towner Act in 1921 and the extension of veterans' health
      benefits in 1924, marked an important step in the development of antagonism
      between the medical community and the federal government during the mid-twentieth
      century.

PMID- 18622073
TI  - Between the ego and the icepick: psychosurgery, psychoanalysis, and psychiatric
      discourse.
AB  - Between the years 1935 and 1965, tens of thousands of lobotomies were performed
      on Americans in order to treat mental illness. This article reconstructs the
      relations between the theory and practice of psychosurgery and a dynamic approach
      to mental illness. The article claims that psychosurgical discourse adopted key
      concepts from psychoanalytical discourse and that psychodynamically oriented
      psychiatrists and psychoanalysts incorporated the basic tenets of psychosurgery
      into their writings. Hence a common, eclectic discourse on psychosurgery was
      created, used by psychodynamically oriented psychiatrists and psychosurgeons
      alike and containing elements from both theories. This article addresses the far
      reaching effects this discourse had on therapeutic practice and on the widespread
      mutual acceptance of psychosurgery. The article questions the distinction between
      somatic and dynamic approaches to mental illness, claiming that the common
      psychiatric discourse indicates that a spectrum of psychiatric thought would
      better describe the state of the profession at the time.

PMID- 18622078
TI  - Adrenergic control of bone remodeling and its implications for the treatment of
      osteoporosis.
AB  - Evidence that leptin regulates bone turnover in part through a central nervous
      system (CNS)/beta-adrenergic system relay has driven attention towards the
      potential therapeutic benefits of beta-adrenergic blockade to improve bone mass
      and strength. beta2- adrenergic receptor-mediated signaling in osteoblasts
      inhibits bone formation and triggers RANKL-mediated osteoclastogenesis and bone
      resorption. Mouse models of adrenergic-deficiency, particularly the mouse lacking
      the beta2-adrenergic receptor, have increased bone mass, more specifically
      increased trabecular bone volume. In turn, beta-blockers, such as propranolol,
      were reported to inhibit ovariectomy-induced bone loss. In contrast, a number of
      experiments in mice and rats suggest that inhibition of beta-adrenergic receptor
      mediated signaling does not improve, and could actually be detrimental, for bone
      mass and microstructure. In humans, epidemiological observations suggested that
      users of beta-blockers have higher bone mineral density (BMD) and/or a reduced
      risk of fractures, yet not all studies were concordant. Here we review the
      evidence for a role of the adrenergic system in the regulation of bone metabolism
      in vitro and in vivo and provide some new evidence for a dual role of beta
      adrenergic receptors 1 and 2 on bone turnover. Furthermore, we will examine the
      similarities and disparities that may exist in the effects of beta-adrenergic and
      PTH stimulation on bone metabolism.

PMID- 18622079
TI  - Effects of beta-blockers on fracture risk.
AB  - Laboratory studies make clear that the sympathetic nervous system does impact on
      bone cell and tissue function. However, these effects are inconsistent between
      models, possibly reflecting sympathetic effects at different levels, from the
      central nervous system through to the bone cells. Observational studies of the
      use of beta-blockers are confounded by the indications for which these drugs are
      prescribed, and by other medications that are commonly co-prescribed with them.
      These data are inconsistent, although a recent meta-analysis did conclude that
      beta-blocker use was associated with a significant decrease in fracture risk.
      However, the more recent studies cast doubt on this finding, and the limited data
      regarding fractures in randomized controlled trials certainly do not support this
      conclusion. Therefore, there is not an adequate evidence base to support using
      beta-blockers as a treatment for osteoporosis, nor can they be regarded as a
      discriminating risk factor for fracture assessment. Until there are definitive
      randomized, controlled trials of beta-blockers, which include fracture as an
      endpoint, it is unlikely that the current confusing situation will be resolved.

PMID- 18622080
TI  - Sympathetic nervous system and bone adaptive response to its mechanical
      environment.
AB  - While bone adaptive response to its mechanical environment was considered to be
      controlled locally by cytokines and systemic hormones, some recent work suggests
      that it could also be neuronally regulated. Bone is indeed very densely
      innervated and many experimental and clinical studies have previously shown the
      involvement of the nervous system in the control of bone metabolism. The
      demonstration that the central nervous system regulates bone mass via the
      sympathetic nervous system (SNS) has prompted recent studies aimed to investigate
      the role of the SNS in the bone mechano-adaptive response. This review will focus
      on this work and summarize the evidence for a contribution of the beta-adrenergic
      signalling in the response of bone cells to mechanical loading. The apparent
      conflicting results obtained in diverse experimental models of loading and
      unloading, at different skeletal sites, and in relation to various hormonal
      levels, will be discussed. While those studies do not support a major influence
      of the SNS on the bone mechano-adaptive response, there is nevertheless strong
      evidence that the SNS is part of a complex system which contributes to the
      metabolic regulation of bone.

PMID- 18622082
TI  - Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition:
      evidence from clinical studies.
AB  - The discovery of a functional serotonin (5-hydroxytryptamine; 5-HT) transporter
      (5-HTT) in bone has given rise to questions about the physiologic role of 5-HT in
      bone, and the possible clinical implications for humans. 5-HT is known to play a
      role in the pathophysiology of depression, and many antidepressant medications
      function by inhibiting the 5-HTT. Among the antidepressants, those that
      selectively block the 5-HTT (namely, selective serotonin reuptake inhibitors;
      SSRIs) appear to have skeletal effects. Several studies have demonstrated lower
      bone density, increased rates of bone loss at the hip, and increased rates of
      fracture among older individuals taking SSRIs. However, there remains uncertainty
      about whether it is the antidepressant medications themselves or the reason for
      their use (depression) that is responsible for these observed bone changes. This
      paper reviews the epidemiologic literature that explores the role of the 5-HTT in
      bone health, by looking at questions about how depression, antidepressant therapy
      and SSRIs impact bone health in humans. Further research will be important to
      better understand how these factors interact to influence skeletal status, and to
      characterize the biochemical mechanism through which 5-HT may mediate bone
      turnover and metabolism.

PMID- 18622081
TI  - Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition:
      evidence from in vitro and animal-based studies.
AB  - The regulation of bone metabolism continues to be an area of intense
      investigation, with recent evidence indicating a potential contribution from the
      neural system. In particular, the neurotransmitter serotonin (5-hydroxytryptamine
      [5-HT]) has been hypothesized to play a role in skeletal metabolism via its
      transporter (5-HTT). The 5-HTT is a plasma membrane transporter that is highly
      specific for the uptake of extracellular 5-HT, thereby facilitating the
      intracellular storage and/or degradation of 5-HT. The 5-HTT is clinically
      important as it is the key target of pharmaceutical agents aimed at treating
      affective disorders, such as major depressive disorder. By antagonizing the 5
      HTT, selective serotonin reuptake inhibitors (SSRIs) potentiate 5-HT activity and
      effectively relieve the symptoms of depression. However, questions have been
      raised regarding the potential skeletal effects of SSRIs given the recent
      identification of a functional 5-HTT and functional 5-HT receptors in bone cells.
      This paper discusses the preclinical evidence for the skeletal effects of 5-HT
      and the inhibition of the 5-HTT. In particular, it discusses the: (1) role of 5
      HT and the function of the 5-HTT; (2) presence of functional 5-HTTs in bone; (3)
      potential sources and response mechanisms for 5-HT in bone, and; (4) in vitro and
      in vivo skeletal effects of 5-HT and 5-HTT inhibition.

PMID- 18622083
TI  - CART deficiency increases body weight but does not alter bone strength.
AB  - The regulation of bone metabolism mediated by leptin is a complex process that is
      not clearly understood. Recent studies suggest that CART (cocaine-amphetamine
      related transcript) is a significant neuronal co-factor when combined with
      leptin. CART deficiency is thought to result in low trabecular bone mass, but
      since leptin exerts contrasting effects on trabecular and cortical bone it is
      possible that cortical bone may not respond to the absence of CART signaling in
      the same manner as trabecular bone. We tested the hypothesis that CART deficiency
      decreases cortical bone mass, density, and strength by examining femora of adult
      wild-type mice (CART(+/+)) and CART-deficient mice (CART(-/-)). DEXA densitometry
      (PIXImus system) was used to measure whole-bone mineral content (BMC) and mineral
      density (BMD) from right femora, and pQCT used to calculate densitometric and
      geometric parameters from the femur midshaft. Femora were also tested in three
      point bending, and sections of the tibia analyzed histologically to determine
      bone marrow adipocyte density (N.At./M.Ar) and endocortical osteoclast number
      (N.Oc/B.Pm). The control mice weighed less than the mice lacking CART (P<0.001),
      but mechanical testing data showed no differences (p>0.05) in ultimate force,
      energy to fracture, stiffness, or intrinsic properties such as ultimate stress,
      ultimate strain, or modulus. CART-deficient mice did not differ from normal
      controls in whole-femur BMC (p=0.09), BMD (p=0.19), midshaft cortical bone
      thickness (p=0.67), midshaft cortical bone area (p=0.59) or N.Oc/B.Pm (p=0.94),
      although CART deficiency was associated with a three-fold increase in bone marrow
      adipocyte density (p<0.001). Our data suggest that while the central,
      neuroendocrine regulation of bone mass via CART signaling may have effects on
      trabecular mass, absence of CART expression does not significantly alter cortical
      bone geometry, density, or strength.

PMID- 18622084
TI  - Osteotropic effects by the neuropeptides calcitonin gene-related peptide,
      substance P and vasoactive intestinal peptide.
AB  - Immunohistochemical phenotypic characterization of skeletal nerve fibers has
      demonstrated the expression of a restricted number of neuropeptides, including
      calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive
      intestinal peptide (VIP). According to the neuro-osteological hypothesis, such
      neuropeptides can be released and exert paracrine biological effects on bone
      cells present close to the nerve endings expressing these signaling molecules.
      The existence of such interplay is most convincingly shown by the hypothalamic
      control of bone formation, in the case of leptin stimulation of hypothalamic
      nuclei mediated by the sympathetic nervous system and inhibitory beta-adrenergic
      receptors on osteoblasts. In addition to these receptors, osteoblasts and
      osteoclasts express functional receptors for CGRP, SP and VIP, which can regulate
      both bone formation and bone resorption. The evidence for these observations is
      summarized in the present paper.

PMID- 18622085
TI  - The role of glutamate in the regulation of bone mass and architecture.
AB  - Communication between the cells in bone underlies the way that the tissue
      functions physiologically, and in nearly all pathologies, the pathogenesis of
      skeletal diseases. The number of molecules involved in intercellular signalling
      in bone grows constantly and it is perhaps unsurprising that the list includes
      many with functions in other tissues. In recent years, evidence has accumulated
      to show that molecules involved in neurotransmission have paracrine roles in the
      skeleton. The focus of this review is the excitatory amino acid glutamate and its
      role in regulating bone formation and resorption. Specifically, this article will
      concentrate on the functional role of the system, and the reasons why mechanisms
      like synaptic transmission are relevant to what might appear to be a slow
      responding tissue, as the sites of expression of glutamate signalling components
      in bone have been reviewed already. While there is strong evidence for a
      regulatory role for glutamate in osteoblast and osteoclast differentiation and
      function in vitro, in vivo data is less advanced. Preliminary data from in vivo
      systems does however suggest that glutamate has a physiological function in the
      skeleton.

PMID- 18622086
TI  - Ten years muscle-bone hypothesis: what have we learned so far?--almost a
      festschrift--.
AB  - The importance of mechanical stimuli for bone is widely appreciated. Mechanostat
      theory proposes a negative feedback system to explain the adaptation of bone by
      homeostatic control of peak strains. However, no assumption is made as to which
      forces cause these strains. Biomechanical analyses suggest that the largest
      forces emerge from muscle contractions, rather than from body weight per se.
      Hence, the idea of a 'muscle-bone' unit emerged ten years ago, proposing that
      bones adapt to muscle strength. This muscle-bone hypothesis is well able to
      account for the accrual of bone mass and strength during childhood, and also to
      explain why certain types of exercise are able to prevent bone loss during
      immobilization. However, the hypothesis fails to explain why exercise becomes
      rather ineffective to increase bone strength after puberty. It is here proposed
      that joint size as a 'third agent' might solve the conundrum. More specifically,
      the assumptions are made that the peak forces determine joint size until the end
      of puberty, and that motor control limits joint reaction forces to critical
      limits during adulthood in order to prevent joint damage. Providing evidence in
      favour or against these conjectures will improve our understanding of the
      musculoskeletal system.

PMID- 18622087
TI  - Whole body vibration in cystic fibrosis--a pilot study.
AB  - INTRODUCTION: In cystic fibrosis (CF), bone mass deficits as well as a lack of
      muscle mass and force have been described. The bone mass deficits are thought to
      be at least in part secondary to the reduced muscle mass. Whole body vibration
      has recently been suggested as an effective technique to increase muscle force
      and power. The aim of this pilot study was to evaluate the compliance and safety
      of a side-alternating, whole body vibration platform in patients with CF and to
      assess its effects on muscle force, muscle power, bone mass and lung function.
      PATIENTS AND METHODS: Eleven adult CF patients participated in a six-months home
      based training programme on a whole body vibration platform. Muscle force and
      power were assessed with three standard manoeuvres on a ground reaction force
      plate at regular intervals. Bone densitometry was performed at the spine, the
      radius and the tibia using quantitative computerized tomography. RESULTS: Regular
      cardiovascular monitoring did not show any critical drop in oxygen saturation or
      blood pressure. Lung function remained relatively constant with a median FEV1
      change [% of norm] of -3.1% (range -7-20). Trabecular density at the spine and
      parameters of bone density and geometry at the radius and tibia did not show
      consistent changes. A median decrease of -0.3% (-31.0-17.9) for muscle force and
      a median increase of 4.7% (-16.4-74.5) for muscle power and 6.6% (-0.9-48.3) for
      velocity was noted in the two-leg jump. In the one-leg jump, a median increase of
      6.7% (-8.5-24.3) for muscle force was measured. CONCLUSIONS: Whole body vibration
      was well tolerated in the majority of the study participants. Most patients were
      able to increase peak force in the one-leg jump. In the two-leg jump, velocity
      and muscle power increased with equal or decreased muscle force. This may
      indicate an improvement in neuromuscular and intramuscular co-ordination (and
      therefore efficiency) with less muscle force necessary to generate the same
      power.

PMID- 18622088
TI  - The influence of auxology and long-term glycemic control on muscle function in
      children and adolescents with type 1 diabetes mellitus.
AB  - We intended to investigate in this pilot-study if long-term glycemic control
      stands in close relationship with muscle function in children and adolescents
      with type 1 diabetes mellitus (T1DM). Muscle function (MIGF, maximal isometric
      grip force; PJF, peak jump force; PJP, peak jump power) was investigated in 40
      children and adolescents (males 20, females 20; age 13.5-/+2.5 yr) affected with
      T1DM. Muscular parameters were correlated with anthropometric parameters (age,
      height, weight) and with glycosylated hemoglobin (HbA1c) of the presence and the
      past. Standard deviation scores (SDSs) of weight and MIGF indicated significantly
      higher weight (mean 0.75-/+1.83 (SD)) and lower MIGF (mean -1.06-/+1.76 (SD)) in
      individuals with T1DM. When the study group was divided into two groups by the
      criteria that the actual HbA1c (HbA1c0) was lower (N=25) or higher (N=15) than
      8.5%, the comparison showed significantly higher muscular parameters (PJF-SDS,
      PJP-SDS and MIGF-SDS) in individuals with higher HbA1c0. Multiple regression
      analyses demonstrated that body weight and height primarily predicted muscle
      force (MIGF, PJF) in T1DM. In conclusion, skeletal growth is an important
      determinant for the development of muscle function in children and adolescents
      with T1DM.

PMID- 18622089
TI  - Lack of association between vitamin D and calcitonin receptor gene polymorphisms
      and forearm bone values of young Greek males.
AB  - INTRODUCTION--HYPOTHESIS: Since the genetic bases of bone mass regulation in
      males are still poorly understood and the role of calciotropic hormones on bone
      mineral metabolism is absolute, our hypothesis is based on the certainty that
      specific genetic polymorphism will contribute, at least, on bone mass values. Our
      objective was to examine the relative contribution of genetic variables to the
      regulation of bone values in a population of young healthy men, focusing on the
      BsmI polymorphism of vitamin D receptor (VDR) gene and the AluI polymorphism of
      calcitonin receptor (CTR) gene. METHODS: Areal bone mineral density (aBMD), bone
      mineral content (BMC) and geometrical areas at specific skeletal sites of the
      forearm, of 301 healthy Caucasian young men, aged 18-25, were assessed by single
      X-ray absorptiometry (Osteometer DTX-100). VDR and CTR alleles were determined by
      BsmI and AluI endonuclease restriction fragment analyses. Analysis of covariance
      was used as a statistical model. RESULTS: No significant differences in the
      forearm aBMD, BMC or in area values were observed between the VDR and CTR
      genotypes. Findings did not change after adjusting for demographic
      characteristics. CONCLUSIONS: The BsmI and AluI polymorphisms are not related to
      the forearm bone values either reflecting mass or geometrical variables in this
      male population.

PMID- 18622090
TI  - Organization and developmental aspects of lymphatic vessels.
AB  - The lymphatic system plays important roles in maintaining tissue fluid
      homeostasis, immune surveillance of the body, and the taking up dietary fat and
      fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many
      pathological conditions, including lymphedema, inflammatory diseases, and tumor
      dissemination. A clear understanding of the organization of the lymphatic vessels
      in normal conditions would be critically important to develop new treatments for
      diseases involving the lymphatic vascular system. Therefore, the present paper
      reviews the organization of the lymphatic vascular system of a variety of organs,
      including the thyroid gland, lung and pleura, small intestine, cecum and colon in
      the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the
      appendix in the rabbit, and human tonsils. Methods employed include scanning
      electron microscopy of lymphatic corrosion casts and tissues with or without
      treatment of alkali maceration technique, transmission electron microscopy of
      intact tissues, confocal microscopy in conjunction with immunohistochemistry to
      some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy
      in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental
      aspects of the lymphatic vessels and lymphedema are also discussed.

PMID- 18622091
TI  - Appearance of LFA-1 in the initial stage of synaptogenesis of developing
      hippocampal neurons.
AB  - In the present study, we found that leucocyte function-associated antigen-1 (LFA
      1), and integrin (heterodimer complex of CD11a and CD18), which are abundant in
      immunological synapse, were expressed in developing hippocampal neurons. The
      expression of LFA-1 in hippocampal neurons was in the period of synaptogenesis,
      and synaptogenesis was inhibited by the blocking antibodies of anti-CD11a or anti
      CD18 in vitro. Since it is known that LFA-1 has an important role in the
      immunological response, especially in immunological synapse, LFA-1 is considered
      to have an important role in neuronal synapse and is highly involved in
      synaptogenesis in the early developmental stage in vitro. In vivo, we also
      confirmed that CD18 was expressed in hippocampus in the early developmental
      stage. Telencephalin, which is a candidate for postsynaptic elements to contact
      LFA-1, was precisely opposed to CD18-positive structures in presynaptic elements,
      and telencephalin was considered to be involved in synaptogenesis. The present
      study showed that 17beta-estradiol of steroid hormones, which are well known to
      have various effects on hippocampal neurons, has a significant influence on the
      presynaptic expression of CD18 in synaptogenesis and inhibited synaptogenesis in
      the early developmental stage in vitro. These results suggest that LFA-1 plays
      some mechanisms in synaptic contacts and synaptogenesis of hippocampal neurons.

PMID- 18622092
TI  - The modulation of collagen fibril assembly and its structure by decorin: an
      electron microscopic study.
AB  - The present study was carried out to determine the effect of decorin in the
      process of collagen assembly. Collagen fibrils were obtained in vitro by
      aggregation from commercialized acid-soluble type I collagen with the addition of
      different concentrations of decorin (0-25 microg/ml). All specimens were observed
      by scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
      The distribution of collagen fibril diameters was also analyzed by TEM. In
      samples without or with low concentrations of decorin, highly porous collagen
      fiber networks were formed. On the other hand, dense networks were observed in
      samples treated with high concentrations of decorin. The influence of decorin
      secreted by cells on collagen fibrils was observed by SEM, and the fiber network
      elasticity was measured using a rheometer. SEM images showed that collagen fiber
      networks without fibroblasts were much looser than those cultured with normal
      fibroblasts. The networks cultured with the fibroblasts were composed of straight
      fibers with large diameters. On the other hand, collagen fiber networks cultured
      with siRNA-decorin-transfected (siDT) fibroblasts had loose, meandering fibers
      with small diameters. The elasticity of collagen fiber networks cultured with
      untransfected fibroblasts showed no significant difference over the 7-day
      incubation period. However, significantly lower elastic values were obtained for
      collagen fiber networks treated with siDT cells on days 3 and 7. In addition,
      after treatment with 5.0 or 25 microg/ml decorin, the l collagen fiber networks
      cultured with siDT cells exhibited an altered structure that showed a dense
      structure similar to that of the fiber networks cultured with untransfected
      fibroblasts. In conclusion, this in vitro study showed that decorin is a
      regulatory and architecturally small leucine-rich repeat proteoglycan in the
      process of collagen fibril assembly.

PMID- 18622093
TI  - The skeletal muscle vascular supply closely correlates with the muscle fiber
      surface area in the rat.
AB  - The skeletal muscle capillary supply (capillarity) dynamically changes in
      response to muscle conditions such as growth, atrophy, and hypertrophy. The
      capillary number-to-fiber ratio is reported to correlate closely with the muscle
      fiber cross sectional area. However, little information is available regarding
      the capillarity of neonatal and very young skeletal muscles. In this study, the
      vascular endothelium was reliably stained with an anti-PECAM-1 antibody, and
      relationships between the capillarity and muscle fiber parameters were analyzed.
      For assessment of the capillarity, we used the capillary length-to-fiber ratio,
      due to the presence of transversely running vessels. In young and adult rats, the
      capillary length-to-fiber ratio was proportional to both the muscle fiber cross
      sectional area and muscle fiber radius. However, when these data were analyzed
      together with data from neonatal and very young rats, the capillary length-to
      fiber ratio correlated more closely with the muscle fiber radius than the muscle
      fiber cross sectional area in the tibialis anterior muscle. The capillary number
      to-fiber ratio demonstrated results very similar to the capillary length-to-fiber
      ratio. During muscle atrophy after denervation, the number of capillaries was
      decreased in a non-apoptotic manner as revealed by electron microscopy,
      maintaining the close relationship between the parameters described above. In
      conclusion, capillarity was closely correlated with the muscle fiber radius
      (which represents the perimeter) during growth and atrophy. This indicates that
      the capillarity is linked to the muscle fiber surface area (which is determined
      by perimeter and section thickness), in agreement with the essential role of the
      cell membrane in the transport of materials by simple diffusion or active
      transport.

PMID- 18622094
TI  - Cell-type specific occurrence of apoptosis in taste buds of the rat circumvallate
      papilla.
AB  - The present study employed immunohistochemistry for single-stranded DNA (ssDNA)
      to detect apoptotic cells in taste buds of the rat circumvallate papilla. Double
      labeling of ssDNA and markers for each cell type - phospholipase C beta2
      (PLCbeta2) and alpha-gustducin for type II cells, neural cell adhesion molecule
      (NCAM) for type III cells, and Jacalin for type IV cells - was also performed to
      reveal which types of cells die by apoptosis. We detected approximately 16.8% and
      14.0% of ssDNA-immunoreactive nuclei among PLCbeta2-immunoreactive and alpha
      gustducinimmunoreactive cells, respectively, but rarely found ssDNA
      immunoreactive cells among NCAM-immunoreactive or Jacalin-labeled cells,
      indicating that type II cells die by apoptosis. We also applied double labeling
      of ssDNA and human blood group antigen H (AbH) - which mostly labels type I cells
      as well as other cell types - and found that approximately 78% of ssDNA
      immunoreactive cells were labeled with AbH, indicating that apoptosis also occurs
      in type I cells. The present results revealed that apoptosis occurs in both type
      I cells (dark cells) and type II cells (light cells), suggesting that there are
      two major cell lineages (dark cell and light cell lineages) for the
      differentiation of taste bud cells. In summury, type IV cells differentiate into
      dark and light cells and type III cells differentiate to type II cells within the
      light cell line.

PMID- 18622095
TI  - [Overview of chemical biology].

PMID- 18622096
TI  - [Cellular imaging by using molecular probes].

PMID- 18622097
TI  - [Chemical biology research on nuclear receptors].

PMID- 18622098
TI  - [Chemical biology of HDAC (histone deacetylase) inhibitors].

PMID- 18622099
TI  - [Development of protein kinase inhibitors and their applications for chemical
      biology].

PMID- 18622100
TI  - [Bioprobe generation from microbial origin for chemical biology study].

PMID- 18622101
TI  - [Pharmacogenomics: challenges in promoting its clinical usage].

PMID- 18622102
TI  - [Vascular toxicology].

PMID- 18622103
TI  - [Pharmacology and clinical results of topiramate (TOPINA Tablets), a new
      antiepileptic drug].

PMID- 18622104
TI  - [Pharmacological and clinical profile of imiquimod (BESELNA CREAM 5%)].

PMID- 18622105
TI  - [Medical problems in middle and high aged man --especially about their QOL
      preservation--].

PMID- 18622106
TI  - [Gender specific medicine for elderly women].

PMID- 18622107
TI  - [Gender issues in elderly care and possible solutions].

PMID- 18622108
TI  - [Heart surgery in elderly patients].

PMID- 18622109
TI  - [Pneumonia in the elderly].

PMID- 18622110
TI  - [An overview: impact of aging in atherosclerosis research].

PMID- 18622111
TI  - [Atherosclerosis and oxidative stress].

PMID- 18622112
TI  - [Sex hormones and atherosclerosis].

PMID- 18622113
TI  - [Contribution of vascular cell senescence to atherogenesis].

PMID- 18622114
TI  - [Ageing and metabolic syndrome].

PMID- 18622115
TI  - [Relationship of metabolic syndrome and insulin resistance with microalbuminuria
      in senior citizens of rural communities in Japan --the Tanno and Sobetsu study-
      ].
AB  - AIM: We investigated the relationship of metabolic syndrome (MetS) and insulin
      resistance (IR) with microalbuminuria in senior citizens of rural communities in
      Japan. METHOD: The subjects were 338 senior citizens (age 65 or older) who
      underwent medical examinations in the towns of Tanno and Sobetsu, Hokkaido in
      2005. The following participants were excluded: those with missing data, those
      with type 2 diabetes (fasting plasma glucose >or=126 mg/dl and/or those who were
      on medication for diabetes), those who were on medication for hypertension and
      those with macroalbuminuria (urinary albumin creatinine ratio (ACR) >or=300
      mg/g.Cr). The subjects were divided into two groups according to the Japanese
      criteria of MetS: a MetS group and a non-MetS group. The percentages of subjects
      with microalbuminuria (ACR >or=30 mg/g.Cr) in the two groups were compared. We
      also investigated the relationship between IR and microalbuminuria using
      homeostasis model assessment (HOMA-R). RESULT: The percentage of subjects with
      microalbuminuria was significantly higher in the MetS group than in the non-MetS
      group. Multiple logistic regression analysis showed that there was a significant
      relationship between MetS and microalbuminuria (relative risk: 3.09, 95%CI: 1.18
      8.07) and that there was also a significant relationship between HOMA-R and
      microalbuminuria (relative risk: 1.91, 95%CI: 1.14-3.20). CONCLUSION: It may be
      important for prevention of microalbuminuria in patients with MetS not only to
      manage blood pressure and blood glucose but also to manage IR, which is part of
      the background of accumulation of these risk factors.

PMID- 18622116
TI  - [Fall risk assessment and knee extensor muscle activity in elderly people].
AB  - PURPOSE: The purpose of this study was to analyze relationships between the
      history of falls, tripping, sway, and knee extensor muscle strengths as a tool
      for fall risk assessment in elderly people. We examined effective fall prevention
      measures. METHODS: We investigated 102 elderly volunteers in the community. The
      subjects were classified according to history of falls, tripping, sway and 5
      performance tests conducted to assess fall risk including Timed up-and-go test
      (TUG), Functional Reach test (FR), Hand grip and Reaction time (RT). In addition,
      the time serial data of the knee extensor muscle strength were acquired using a
      hand-held dynamometer. RESULTS: In comparison to the non-faller group, the faller
      group showed a significantly higher incident rate of tripping and sway. A
      frequency analysis using the Maximum Entropy Method revealed that the fallers
      group showed lower peak frequency (p=0.025). Also, the slope of the logarithmical
      spectrum was less steep in the fallers group (p=0.035). Also results from
      analysis of the peak force latency from the beginning of measurement to 50%, 80%,
      and 100% muscle strength, also showed that the faller group took more time for
      maximal voluntary contraction. CONCLUSIONS: The frequency analysis of the time
      series date of peak force latency of knee extensor muscle strength revealed that
      the muscle activity differs in faller compared to non-fallers. This study
      suggested that knee extensor muscle isometric performance could possibly be used
      as a new tool for fall risk assessment. We concluded that exercises to raise
      maximal muscle strength and muscle response speed are useful for the prevention
      of falls.

PMID- 18622117
TI  - [Risk factors associated with urinary incontinence in community-dwelling elderly
      women].
AB  - AIM: To evaluate whether the frequency, volume, and type of urinary incontinence
      (UI) correlated with physical fitness and self-rated health, and to assess the
      risk factors associated with frequency and volume of UI, and self-rated health in
      elderly community-dwelling women with UI. METHODS: The subjects were 957 women
      aged 70 or older who participated in a comprehensive health examination which
      included a face-to-face interview and physical fitness tests. In order to
      evaluate the differences in the physical fitness and the interview data with the
      frequency, volume, and type of UI we used student t-test for continuous variables
      and the chi-square test for categorical variables. Multivariate logistic
      regression models were used to assess the factors associated with frequency and
      volume of UI, and self-rated health. RESULTS: The prevalence of UI was 43.5% in
      elderly women. The high frequency and large amount of UI, and the urge and mixed
      UI were significantly associated with a lower level of balance, muscular
      strength, walking ability, and higher BMI. According to the logistic model, self
      rated health (odds ratio (OR)=0.49, 95%confidence intervals (CI)=0.26-0.92), urge
      (OR=2.04, 95%CI=1.04-4.06) and mixed UI (OR=4.07, 95%CI=1.94-8.70), BMI (OR=1.10,
      95%CI=1.01-1.21), urination frequency during the daytime(OR=1.25, 95%CI=1.10
      1.44), maximum walking speed (OR=0.25, 95%CI=0.08-0.71) were independent
      variables significantly associated with frequency of UI, the volume of UI was
      significantly associated with urge (OR=2.27, 95%CI=1.08-4.91) and mixed UI
      (OR=3.02, 95%CI=1.33-6.98), and the self-rated health was significantly
      associated with frequency of UI (OR=2.18, 95%CI=1.28-3.68) and urge UI (OR=2.28,
      95%CI=1.30-4.06). CONCLUSIONS: The high frequency and urge UI was significantly
      associated with a lower level of physical fitness and self-rated health. Our
      findings suggest that active lifestyle, which was focused on a decreased BMI and
      increased walking ability, may contribute to the prevention of UI.

PMID- 18622118
TI  - [Development of the Japanese version Care Planning Assessment Tool (J-CPAT):
      reliability and validity studies].
AB  - AIM: To develop a Japanese version Care Planning Assessment Tool (CPAT) , a
      comprehensive geriatric assessment instrument for dementia care, originally
      developed in Australia. METHODS: The J-CPAT is composed of 61 items, and 8
      domains: Communication, Physical problems, Self-help skills, Confusion, Behavior,
      Social interaction, Psychiatric observation, and Care dependency. The development
      of the J-CPAT included translation into Japanese, assessment of item
      comprehension, back translation, production of final version, and its validity
      and reliability analysis. Through this process, an item about family interaction
      was added in the J-CPAT. The participants were 199 clients in residential and day
      care. Raters were professional carers with 2.5 hours training about the J-CPAT.
      We assessed the validity of the J-CPAT, using correlation between the scores of
      the J-CPAT, MMSE, NM-scale, N-ADL, and levels of care needs (Kaigodo). Ten pairs
      of carers were included in the inter-rater reliability analysis. Fourteen carers
      participated in the intrarater reliability study. RESULTS: Cronbach's alpha
      values in each J-CPAT domain were 0.74-0.95. Mean difference of each domain
      between test and retest was 0.4-3.6%. Weighted kappa values for all items for 10
      pairs of raters were over 0.6. The correlation coefficients between the domain
      score of 'Confusion' in the J-CPAT and MMSE was -0.90 (p<0.01). Those between the
      domain scores of 'Physical problems', 'Self-help skills', 'Dependency on care' in
      the J-CPAT, and Kaigodo were sufficient (>0.62), and those between the item
      scores of the J-CPAT, NM-scale, and N-ADL were relevant (>0.60). CONCLUSIONS: The
      J-CPAT is considered to be an appropriate assessment instrument for dementia care
      in Japan.

PMID- 18622119
TI  - [Characteristics of heat illness in older people].
AB  - AIM: As summer become hotter due to rapid climate change, older people suffering
      from heat illness are increasing. The aim of our study was to examine the
      characteristics of older people who suffered from heat illness. METHODS: We
      analyzed the 65 years or older patients admitted for acute care of Nagoya
      Ekisaikai Hospital via the emergency department (ED) during the summer seasons of
      2006 and 2007. Demographic data, functional status, use situation of care
      services, climate of the onset day, use of an air conditioners, and cognitive
      status, length of hospital stay and disposition following their discharge were
      recorded. RESULTS: During the study period, 104 patients visited the ED because
      of heat illness. Twenty older patients were admitted for acute care. In
      hospitalized patients, the mean length of stay was 27.5+/-18.6 days. Sixty
      percent of patients were discharged to long-term care facilities (12/20). Sixteen
      patients suffered from heat illness inside their home. Most of the patients had
      characteristics such as living alone or with their spouses only (14/16),
      cognitive dysfunction (12/16), lack or no use of an air conditioner (11/16) , no
      use of care service (11/16) , and preserved functional status (10/16) .
      CONCLUSIONS: Many older patients suffered from heat illness in their home, and
      their ED visits were associated with prolonged admissions and post-discharge
      institutionalizations. It is important to give education to prevent heat illness
      in older people.

PMID- 18622120
TI  - [A case of pernicious anemia with type A gastritis in an extremely elderly
      patient with dementia and heart failure].
AB  - A 90-year-old woman was referred and admitted to our hospital because of
      progressing dementia, decreased appetite, and general fatigue. Blood tests on
      admission disclosed: white cell count, 2,900 /mm(3); hemoglobin 5.6 g/dl; mean
      corpuscular volume; 139.7 microm(3). Based on the presence of pancytopenia,
      macrocytic anemia, and elevated lactate dehydrogenises, we suspected pernicious
      anemia. We administered vitamin B12, which improved the blood test results and
      the signs of dementia. Gastrointestinal tract examination showed type A
      gastritis. Tests for anti-intrinsic factor antibody and anti-gastric parietal
      cell antibody were positive, which help confirm a diagnosis of pernicious anemia.
      Pernicious anemia is an autoimmune disease common among those aged 50-60 years.
      Cases aged over 90 years are rare. However, the numbers of extremely elderly
      patients are expected to increase with the growth of the elderly population.
      Fortunately, pernicious anemia is easy to treat. We need to make an appropriate
      diagnosis of pernicious anemia in the oldest elderly patients.

PMID- 18622121
TI  - [Successful treatment of non-small cell lung cancer by gefitinib in an elderly
      patient with poor performance status].
AB  - A 91-year-old woman was admitted to our hospital with dyspnea. A chest radiograph
      and chest CT films revealed a large amount of pleural effusion in the right side
      pleural cavity. After serial thoracentesis, chest CT films showed a mass shadow
      in the right S(6). Adenocarcinoma cells were found in the pleural effusion,
      leading to a diagnosis of non-small cell lung cancer (stage IIIB). After
      administration of gefitinib, the mass shadow and pleural effusion reduced and her
      performance status improved. Gefitinib may be a well-tolerated therapeutic
      strategy in elderly and poor performance status patients with advanced non-small
      cell lung cancer.

PMID- 18622122
TI  - [Standardization and individualization of end-of-life care for elderly at long
      term care facilities].

PMID- 18622124
TI  - Packing density of glycolipid biosurfactant monolayers give a significant effect
      on their binding affinity toward immunoglobulin G.
AB  - Mannosylerythritol lipid-A (MEL-A) is one of the most promising glycolipid
      biosurfactants, and abundantly produced by Pseudozyma yeasts. MEL-A gives not
      only excellent self-assembling properties but also a high binding affinity toward
      human immunoglobulin G (HIgG). In this study, three kinds of MEL-A were prepared
      from methyl myristate [MEL-A (m)], olive oil [MEL-A (o)], and soybean oil [MEL-A
      (s)], and the effect of interfacial properties of each MEL-A monolayer on the
      binding affinity toward HIgG was investigated using surface plasmon resonance
      (SPR) and the measurement of surface pressure (pi)-area (A) isotherms. Based on
      GC-MS analysis, the main fatty acids were C(8) and C(10) acids in all MEL-A, and
      the content of unsaturated fatty acids was 0% for MEL-A (m), 9.1% for MEL-A (o),
      46.3% for MEL-A (s), respectively. Interestingly, the acid content significantly
      influenced on their binding affinity, and the monolayer of MEL-A (o) gave a
      higher binding affinity than that of MEL-A (m) and MEL-A (s). Moreover, the mixed
      MEL-A (o)/ MEL-A (s) monolayer prepared from 1/1 molar ratio, which comprised of
      27.8% of unsaturated fatty acids, indicated the highest binding affinity. At the
      air/water interface, MEL-A (o) monolayer exhibited a phase transition at 13
      degrees C from a liquid condensed monolayer to a liquid expanded monolayer, and
      the area per molecule significantly expanded above 13 degrees C, while the amount
      of HIgG bound to the liquid expanded monolayer was much higher than that bound to
      liquid condensed monolayer. The binding affinity of MEL-A toward HIgG is thus
      likely to closely relate to the monolayer packing density, and may be partly
      controlled by temperature.

PMID- 18622125
TI  - Adsorption of cationic monomeric and gemini surfactants on montmorillonite and
      adsolubilization of vitamin E.
AB  - Adsorption of a cationic gemini surfactant (1,2-bis(dodecyldimethylammonio)
      ethane dibromide, 12-2-12) and the corresponding monomeric surfactant
      (dodecyltrimethylammonium bromide, DTAB) on montmorillonite has been
      characterized with a combination of adsorption isotherm, interlayer spacing and
      FT-IR spectroscopic data. Adsolubilization of vitamin E into the adsorbed
      surfactant layers has also been studied. The adsorption isotherm data reveal that
      the adsorption of the two surfactants is driven by the two factors: one is the
      cation exchange that occurs on the interlayer basal planes and the other is the
      hydrophobic interaction between hydrocarbon chains of the surfactants. Although
      the adsorbed amount measured in the saturation region (in mol g(-1)) is almost
      identical for the two surfactants, the conformation of the intercalated
      surfactant molecules differs significantly from each other. The adsorption of
      DTAB results in a lateral bilayer arrangement in the limited interlayer space,
      whereas 12-2-12 gives a normal bilayer arrangement in the expanded interlayer
      space. Adsolubilization of vitamin E takes place into the adsorbed surfactant
      layers, and interestingly, all the vitamin E molecules added in the
      montmorillonite suspensions are hybridized at lower surfactant concentrations due
      to the great specific surface area of the clay material. Since the maximum
      adsolubilization amount is usually obtained just below the critical micelle
      concentration, the gemini surfactant is deemed to be more efficient than the
      corresponding monomeric one to achieve the great adsolubilization amount.

PMID- 18622126
TI  - Alpha-glucosidase inhibitor from Bergenia ligulata.
AB  - Inhibitory compound of alpha-glucosidase activity, (+)-afzelechin (1), was
      isolated from rhizomes of Bergenia ligulata. The structure was identified by IR,
      EI-MS, (1)H and (13)C NMR spectroscopy. The ID(50) (50% inhibition dose) value of
      compound 1 was 0.13 mM. To investigate the structure-activity relationship, (+)
      afzelechin tetraacetate (2), (+)-5,7,4'-trimethoxyafzelechin (3), (+)
      tetramethoxyafzelechin (4), and (+)-3-acetyl-5,7,4'-trimethoxyafzelechin (5) as
      the derivatives of compound 1 were evaluated as well.

PMID- 18622127
TI  - An efficient synthesis of five-membered cyclic ethers from 1,3-diols using
      molecular iodine as a catalyst.
AB  - Intramolecular cyclic etherification of 1,3-diols was investigated using iodine
      as a catalyst under solution reaction conditions. Compounds containing five
      membered ether rings were obtained. Propella ether (11
      oxatricyclo[4.4.3.0(1,6)]tridecane) was conveniently synthesized from 1,3-diol (6
      (2-hydroxyethyl)spiro[4.5]decan-6-ol) in 97% yield via carbon skeleton
      rearrangement. Spiroethers and bicyclic ethers were also obtained from the
      corresponding 1,3-diols in yields of over 77%. The most suitable reaction
      conditions were a temperature of 80 degrees C, a 1:0.2 molar ratio of 1,3
      diol:iodine, and a time period of 8 h. In addition, terpenoic ethers were
      efficiently synthesized from the corresponding 1,3-diols, derived from (+)
      camphor and (-)-fenchone, via skeleton rearrangement. In particular, the reaction
      of the 1,3-diol derived from (+)-camphor proceeded smoothly at room temperature
      with a yield of 91%. The yield of the cyclic ether using iodine as a catalyst was
      comparable to the method using sulfuric acid.

PMID- 18622128
TI  - Synthesis and antibacterial activity of quaternary ammonium salt-type
      antibacterial agents with a phosphate group.
AB  - Quaternary ammonium salts are frequently used as antibacterial agent that
      disrupts cell membrane through the binding of their ammonium cations to anionic
      sites in the outer layer tissue of bacteria. This article describes the synthesis
      of quaternary ammonium salt-type antibacterial agents with a phosphate group that
      strongly binds to hydroxyapatite and bromide ion as counterion. Evaluation of the
      antibacterial activity of the synthesized compounds in terms of minimum
      inhibitory concentration (MIC test) showed that the compounds exhibit an
      excellent antibacterial activity on a variety of bacteria including Gram-positive
      and Gram-negative bacteria, yeast, and fungi.

PMID- 18622129
TI  - Facile one-pot synthesis of N-acyl-1H-1,2,3-benzotriazoles from internal and
      terminal olefinic fatty acids and their antimicrobial screening.
AB  - N-acyl-1H-1,2,3-benzotriazoles were prepared in good yields by the reaction of
      benzotriazole and thionyl chloride with olefinic fatty acids under mild reaction
      conditions. The new compounds 1-(undec-10-enoyl)-1H-1,2,3-benzotriazole (5a),1
      [(Z)-octadec-9-enoyl]-1H-1,2,3-benzotriazole (5b), 1-[(9Z,12R)-12-hydroxyoctadec
      9-enoyl]-1H-1,2,3-benzotriazole (5c), 1-[(9R,12Z)-9-hydroxyoctadec-12-enoyl]-1H
      1,2,3-benzotriazole (5d) formed were characterized on the basis of elemental
      analysis and spectral data. All the newly synthesized compounds (5a-5d) were
      screened for their antimicrobial activity and showed good antifungal activity.

PMID- 18622130
TI  - Preparation of ethyl magnesium bromide for regiospecific analysis of
      triacylglycerols.
AB  - This paper presents a procedure for preparation of a Grignard reagent, ethyl
      magnesium bromide, used for partial deacylation of triacylglycerols (TAG) in
      their regiospecific analysis. Magnesium turnings were reacted with ethereal
      solution of bromoethane in a screw-capped test tube to synthesize 2 mL of 1 M
      ethyl magnesium bromide. Continuously stirred with a vortex mixer, the reaction
      smoothly proceeded at room temperature. Regiospecific analysis of 1,3-distearoyl
      2-oleoylglycerol using this product showed that fatty acid compositions of the sn
      1(3) and sn-2 positions were contaminated by less than 2 mol% of fatty acids
      migrated from isomeric positions. The analyses of lard and cod liver/mackerel oil
      TAG showed typical distribution patterns of 16:0, 22:5n-3 and 22:6n-3 in pig and
      fish depot TAG. These results confirmed the view that the freshly prepared
      reagent is usable for regiospecific analysis of TAG.

PMID- 18622131
TI  - Comparison of the radiobiological effect of carbon ion beam therapy and
      conventional radiation therapy on cervical cancer.
AB  - Little clinical evidence has been provided to show the minimization of radiation
      resistance of tumors using high linear energy transfer radiation. We therefore
      investigated the radiobiological and molecular pathological aspects of carbon
      beam therapy. A total of 27 patients with squamous cell carcinoma (SCC) of the
      cervix were treated using a carbon beam and 50 control patients with SCC of the
      cervix using a photon beam. The expression of Ki-67, p53, and p27 proteins before
      radiotherapy and 5 and 15 days after therapy initiation were investigated using
      immunohistochemistry. Similar changes were observed in Ki-67 labeling index (LI)
      and p53 LI during carbon and photon beam therapies. However, for carbon beam
      therapy, the mean p27 LI significantly decreased from 25.2% before treatment to
      18.6% on the 5th day after treatment initiation, followed by a significant
      increase to 36.1% on the 15th day. In contrast, for photon beam therapy, the p27
      LI consistently decreased from the initial 19.9% to 13.7% on the 15th day.
      Histological effects were observably stronger under carbon than photon beam
      therapy, though no statistically significant difference was observed (p = 0.07 on
      the 5th day and p = 0.10 on the 15th day). The changes in p27 LI under carbon
      beam therapy were significantly different from those under photon beam therapy,
      which suggests important molecular differences in the radio-biological response
      between therapies. Further investigation is required to elucidate the clinical
      relevance of these putative changes and optimize the relative biological
      effectiveness of carbon beam to X-ray.

PMID- 18622132
TI  - [Diagnosis-the dark page of (scientific) complementary medicine].

PMID- 18622133
TI  - [Treatment with crystal singing bowls for chronic spinal pain and chronobiologic
      activities - a randomized controlled trial].
AB  - INTRODUCTION: This prospective randomized controlled trial examined the effect of
      harmonic vibrations of crystal singing bowls on the perception of pain,
      subjective wellbeing and chronobiologic activities (quality of sleep) in patients
      with chronic unspecific spinal pain. SUBJECTS AND METHODS: 54 persons with
      chronic, unspecific spinal pain participated in the study. The treatment group
      (IG) received 6 units of a singing bowl therapy, the placebo group (KG) received
      a placebo treatment. The control group (NG) was not treated at all. Pain
      intensity, pain disability and quality of life were evaluated right before and 1
      week after the intervention, pulse rate and skin conductance were measured during
      3 therapeutic sessions. A 24-hour measurement of the heart rate variability to
      evaluate quality of sleep was made four times. Before and after each session the
      Multidimensional Mood State Questionnaire (MDBF) was filled out. RESULTS: IG and
      KG had significant lower pain intensities compared to the NG. The NG even
      experienced an increase in pain intensity. The results of the MDBF suggest an
      unspecific relaxing effect of the intervention in IG and KG. Twice during the
      treatment a significant decrease of the pulse rate could be observed. CONCLUSION:
      Under the given conditions the hypothesis of pain relief and chronobiologic
      changes in patients with chronic spinal pain by a treatment with crystal singing
      bowls compared to placebo could not be confirmed.

PMID- 18622134
TI  - [Integrative therapy of a patient with complex psychosomatic complaints].
AB  - We present the case of a 76-year-old female patient with complex psychosomatic
      complaints. The patient suffered from depression, panic attacks, chronic pain and
      dyspepsia with nausea and loss of appetite. In addition to the conventional
      psychosomatic care, the patient received individual homeopathic treatment for her
      dyspepsia, resulting in complete remission. The therapeutic value of homeopathy
      in the present case is discussed in the context of recent findings from placebo
      research.

PMID- 18622135
TI  - [Sleep, mental guardians of peace. 9th Symposium on the ratio and plausibility in
      naturopathy, 8 December 2007, Jena, Germany].

PMID- 18622136
TI  - Relationship between lipoprotein(a), metabolic syndrome, and carotid
      atherosclerosis in older Japanese people.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] or metabolic syndrome (MS) is individually
      considered an atherosclerotic factor. Serum Lp(a) may reportedly show the
      additive effects on atherosclerosis under certain particular pathologies. We do
      not know the association between serum Lp(a) and carotid artery intima-media
      thickness (CIMT) with relation to MS in older people. OBJECTIVE: The present
      study aims at investigating the relationship between Lp(a) and CIMT levels in
      relation to MS among older subjects. METHODS: We studied 182 Japanese subjects of
      >or=60 years (mean 72.5 years), free of cardiovascular/cerebrovascular disease.
      MS was based on the NCEP-ATPIII criteria with a minor modification for Japanese.
      The CIMT was ultrasonographically measured. RESULTS: The CIMT levels were
      significantly greater in the MS group (n = 60, 1.03 +/- 0.22 mm) than the non-MS
      group (n = 122, 0.96 +/- 0.22 mm). Multivariate analysis, using Lp(a) levels or
      the product term for interaction between Lp(a) and MS, showed that age
      significantly and independently correlated to CIMT, along with male gender.
      DISCUSSION: Even when Lp(a) and MS were simultaneously considered, age was the
      best determinant of CIMT in this population. The mechanism of our results
      including weak additive effects of Lp(a) and MS among older subjects may be
      partly throughout aging.

PMID- 18622137
TI  - Cameron lesions: unusual cause of gastrointestinal bleeding and anemia.
AB  - Cameron lesions are linear gastric ulcers or erosions on the mucosal folds at the
      diaphragmatic impression in patients with a large hiatal hernia. The clinical
      relevance of Cameron lesions is due to their potential complications such as
      gastrointestinal bleeding (acute, chronic and obscure) and anemia. The diagnosis
      is usually made during upper endoscopy. Medical therapy is the mainstay of
      treatment with few cases reserved for surgical correction.

PMID- 18622138
TI  - Tumor necrosis factor-alpha develops late anaphylactic reaction through cytosolic
      phospholipase A(2) activation.
AB  - BACKGROUND: We have recently reported that tumor necrosis factor (TNF)-alpha
      plays an important role in the development of a late anaphylactic reaction, but
      the downstream pathway beyond TNF-alpha remains unclear. OBJECTIVE: It was the
      aim of this study to examine whether TNF-alpha induces late-phase anaphylaxis via
      the activation of cytosolic phospholipase A(2) (cPLA(2)). METHODS: Using a murine
      model of active systemic anaphylaxis to penicillin V, the induction of the late
      phase of anaphylaxis was quantified by measuring the increase in hematocrit value
      as well as the plasma level of platelet-activating factor in TNF-alpha knockout
      mice. Phosphorylation of mitogen-activated protein kinases (MAPKs) and cPLA(2)
      was measured by immunoprecipitation. cPLA(2) activity was assessed by using 1
      stearoyl-2-[1-(14)C] arachidonyl-sn-glycero-3-phosphocholine as the substrate.
      RESULTS: Phosphorylation and enzymatic activity of cPLA(2), and phosphorylation
      of the 3 known MAPKs, i.e. p38, extracellular signal-regulated kinase 1/2
      (ERK1/2) and c-Jun NH2-terminal kinase, were markedly increased in a TNF-alpha
      dependent way in the lungs of mice undergoing anaphylaxis. A specific cPLA(2)
      inhibitor significantly attenuated the late anaphylactic symptoms. Either p38 or
      an ERK inhibitor significantly attenuated not only cPLA(2) phosphorylation and
      activity, but also the late-phase anaphylaxis. CONCLUSION: TNF-alpha-induces
      cPLA(2) activation through the pathway involving p38 MAPK and ERK activation and
      appears to be the key mechanism leading to the development of late-phase
      anaphylaxis.

PMID- 18622139
TI  - Intranasal mometasone furoate alleviates the ocular symptoms associated with
      seasonal allergic rhinitis: results of a post hoc analysis.
AB  - BACKGROUND: Burdensome symptoms of allergic rhinitis (AR) include nasal and
      ocular symptoms such as itching, tearing and redness. Intranasal corticosteroids
      are efficacious in the treatment of nasal symptoms of AR. OBJECTIVE: It was the
      aim of this study to determine the efficacy of the intranasal corticosteroid
      mometasone furoate nasal spray (MFNS) in relieving ocular symptoms associated
      with seasonal AR (SAR). METHODS: Ocular symptom data were analyzed for subjects
      >or=12 years of age, randomized to MFNS 200 mug q.d. (n = 176) or placebo (n =
      177) in a placebo-controlled, double-blind clinical trial. Post hoc efficacy
      analysis assessed the mean change from baseline in subject-reported total ocular
      symptom scores (TOSS) averaged over the treatment period. RESULTS: Mean baseline
      TOSS was 4.91 for the MFNS group and comparable (5.05) for the placebo group -
      combined average for individual symptoms such as itching, tearing and redness
      ranged from 0 (no symptoms) to 9 (all symptoms, severe). Mean change from
      baseline in TOSS averaged over days 1-15 was -1.42 for the MFNS group and -0.94
      for the placebo group (p = 0.02), for an observed treatment difference of 0.49
      (statistical data rounded to 2 decimal positions). Improvement in individual
      symptoms (eye itching, tearing and redness) contributed to this treatment effect;
      the greatest improvement occurred with tearing, which decreased -0.52 from the
      baseline score 1.59 in the MFNS group and -0.31 from 1.67 in those receiving
      placebo (p < 0.01), for an observed treatment difference of 0.21. Treatment with
      MFNS was safe and well tolerated. CONCLUSION: MFNS is effective in reducing
      ocular symptoms of SAR, in addition to its established efficacy in reducing nasal
      symptoms of SAR.

PMID- 18622141
TI  - Prevention of mast cell activation disorder-associated clinical sequelae of
      excessive prostaglandin D(2) production.
AB  - BACKGROUND: Patients with systemic mastocytosis have increased numbers of mast
      cells in the bone marrow and other organs, such as the liver, spleen,
      gastrointestinal tract and skin. Symptoms result from the local and remote
      effects of mediator release from mast cells and from the local effects of
      increased mast cell numbers in various organs. Patients with mast cell activation
      experience many of the same clinical symptoms as do patients with systemic
      mastocytosis from chronic or spontaneous release of mast cell mediators. We
      report 4 patients with mast cell activation symptoms from selective release of
      prostaglandin (PG) D(2), but not histamine, and their improvement with aspirin
      therapy. METHODS: Bone marrow biopsy specimens obtained from 4 patients with
      symptoms suggestive of mastocytosis were examined by tryptase immunostaining.
      Baseline levels of serum tryptase and urinary 11beta-PGF(2)(alpha) and N
      methylhistamine were obtained. In 2 of the 4 patients, urinary 11beta
      PGF(2)(alpha) and N-methylhistamine samples were also measured during acute
      symptoms. RESULTS: Baseline increase in urinary excretion of the PGD(2)
      metabolite 11beta-PGF(2)(alpha) was found in 2 patients. In the remaining 2
      patients, baseline levels of urinary 11beta-PGF(2)(alpha) and N-methylhistamine
      were normal, but during acute symptoms, the excretion of 11beta-PGF(2)(alpha)
      increased markedly. Treatment with aspirin resulted in normalization of 11beta
      PGF(2)(alpha) excretion in the 2 patients with elevated baseline levels and in
      prevention of symptoms in all 4 patients. CONCLUSIONS: These results suggest that
      mast cell activation may be manifested by a selective excessive release of
      PGD(2). These patients respond to administration of aspirin but not to
      antihistamines.

PMID- 18622140
TI  - Hepatocyte growth factor suppresses production of reactive oxygen species and
      release of eosinophil-derived neurotoxin from human eosinophils.
AB  - BACKGROUND: Reactive oxygen species (ROS) and eosinophilic granule proteins such
      as eosinophil-derived neurotoxin (EDN) are known to damage bronchial tissue and
      cause airway hyperresponsiveness (AHR) in asthma. Hepatocyte growth factor (HGF)
      regulates various biological activities and is known to be a multifunctional
      factor. In our previous study, we found that HGF suppressed allergic airway
      inflammation and AHR in a murine model of asthma. However, there have been few
      reports regarding the detailed mechanism of the anti-allergic effect of HGF in
      asthma. In this study, we investigated the potential of recombinant HGF to
      regulate the production of ROS and the release of EDN from human eosinophils.
      METHODS: Eosinophils were isolated from subjects with mild eosinophilia by
      modified CD16-negative selection. We investigated the expression of CD69, an
      activation marker of eosinophils, on eosinophils, using flow cytometry. Further,
      ROS production from eosinophils was analyzed using luminol-dependent
      chemiluminescence, and EDN release was measured by ELISA. RESULTS: Treatment with
      HGF suppressed interleukin-5-induced upregulation of CD69 expression, ROS
      production and EDN release from human eosinophils. CONCLUSION: Taken together,
      these data suggest that in asthma, HGF attenuates allergic airway inflammation
      and AHR through at least the suppression of ROS production and EDN release from
      eosinophils.

PMID- 18622142
TI  - Predictive factors of attrition in a cohort of Alzheimer disease patients. The
      REAL.FR study.
AB  - BACKGROUND: Attrition, i.e. patient dropout, can threaten the validity of results
      in longitudinal studies. The aim of this study was to identify patient and
      caregiver factors predictive of attrition in a cohort of Alzheimer disease (AD)
      patients. METHODS: 686 patients with mild to moderate AD were included in the
      multicenter prospective REAL.FR study. Standardized gerontological evaluations
      were carried out twice yearly. Factors associated with attrition were assessed by
      survival analysis using a Cox proportional hazard model. RESULTS: After 2 years,
      278 (40.5%) patients had dropped out. Causes of attrition included refusal
      (20.9%), death (20.1%), institutionalization (19.8%), and loss to follow-up
      (19.8%). Attrition rates between each 6-month wave were constant at 12%. After
      adjustment, several independent factors remained associated with attrition:
      patients cared for by an unrelated caregiver [HR 1.7; 95% CI (1.08-2.59)], loss
      of autonomy [HR = 1.37; (1.03-1.82)], increasing caregiver burden [HR = 1.014;
      (1.005-1.022)], use of cholinesterase inhibitors [HR = 0.40; (0.27-0.59)], use of
      1 to 3 other types of medication [HR = 0.57; (0.36-0.89)]. CONCLUSIONS: The
      identification of both patient and caregiver factors predictive of attrition is
      of particular interest for the development and targeting of attrition prevention
      strategies. In patients with chronic diseases, particular attention should be
      paid to caregiver well-being to limit attrition.

PMID- 18622143
TI  - Mortality after a diagnosis of dementia in a population aged 75 and over in
      Spain.
AB  - OBJECTIVES: To examine the impact of incident dementia on the risk of death,
      taking into account other chronic illnesses potentially related to death. DESIGN:
      Six-year, prospective, two-phase, observational cohort study. SETTING: 8
      municipalities from a rural area in Girona (Spain). PARTICIPANTS: A
      representative community-based cohort of 1,153 adults aged over 70 living at home
      at study enrolment. MEASUREMENTS: Surviving participants underwent detailed
      clinical evaluation and were assessed by means of the Cambridge Examination for
      Mental Disorders of the Elderly. Relatives of deceased participants were
      interviewed using the Retrospective Collateral Dementia Interview. Mortality
      rates and relative risk of death for subjects with a diagnosis of dementia were
      calculated. The Cox proportional hazards regression model was used to assess the
      relationship between mortality and the diagnosis of dementia. RESULTS: In this
      cohort, 40.0% (n = 49) of the subjects with a diagnosis of dementia died. The
      mortality rate specific to dementia was 1.0 per 100 person-years. Mortality risk
      ratios for dementia were 1.79 in men [95% confidence interval (CI) = 1.06-3.02],
      and 3.14 in women (95% CI = 2.04-4.85). The population death risk attributable to
      the diagnosis of dementia in our cohort was 11.8%. The most important mortality
      risks were severe dementia (hazard ratio = 5.7, 95% CI = 3.7-8.6), cancer (hazard
      ratio = 3.2, 95% CI = 2.2-4.5), heart disease, and an age over 85 (hazard ratio =
      1.4, 95% CI = 1.1-1.9). CONCLUSION: Dementia is a major risk factor for death in
      advanced age, with the highest mortality rates in women. Moderate and severe
      dementia was associated with an increased mortality risk even after appropriate
      control of comorbid conditions.

PMID- 18622144
TI  - Prothrombotic gene variation in patients with large and small vessel disease.
AB  - The classification of ischemic stroke into different subtypes is supported in
      genetic association studies. While several gene variants have been identified as
      being associated with ischemia subtypes, most studies have not been powered to
      study subtypes separately. We investigated 887 patients with nondisabling
      cerebral ischemia of arterial origin and classified ischemia as being caused by
      large or small vessel disease (LVD or SVD), primarily based on neuroimaging
      findings. In total, 621 patients had LVD and 266 SVD. The coagulation factor XIII
      subunit B gene (F13B) His95Arg variant was more common in patients with LVD (mean
      prevalence difference 9.9%; 95% CI 4.7-15). None of 21 other prothrombotic gene
      variants was associated with LVD or SVD. Many gene variants may not be specific
      for one subtype. We could not replicate the genetic associations identified in
      previous smaller previous studies. Thus claims about genetic associations with
      specific subtypes of ischemia should be interpreted with caution. The association
      between F13B His95Arg and LVD requires replication.

PMID- 18622146
TI  - Status of influenza vaccination in patients presenting to two neighborhood
      primary health care clinics in Antalya.
AB  - The objective of our study was to determine the status of influenza vaccination
      in patients presenting to two neighborhood primary health care clinics at the
      provincial centre of Antalya. This type of descriptive research was conducted
      between March 15 and April 15, 2006, at Primary Health Care Clinics Number 9 and
      16 in Antalya. A prepared questionnaire was completed by Akdeniz University
      Medical Faculty intern physicians during face-to-face interviews with 1494
      patients. Information about infants and children were obtained from their
      parents. Data that were obtained were evaluated using the SPSS program. It was
      determined that 7.4% (111 individuals) of the research group had been vaccinated
      against influenza. Although there were no infants between 6 - 23 months who had
      been vaccinated, the percentage of individuals in the older than 60 yrs group who
      had been vaccinated was 27.9%. The vaccination status was significantly higher in
      the 60+ age group (p <0.001), in university graduates (p<0.001), in civil
      servants, in those with health insurance (p<0.025) and in those who had any kind
      of risk (p<0.001). It was determined that 24.6% of the research group had had
      influenza in the last month. In those at risk of catching influenza the
      vaccination rate was 14.9%. In the research group 27.3% of the chronic
      obstructive pulmonary disease (COPD) patients, 21.3% of the chronic
      cardiopulmonary disease patients, 18.0% of those with asthma, and 13.4% of the
      individuals with diabetes mellitus had received the influenza vaccination. It is
      recommended that all health care personnel working in primary health care clinics
      must educate the public about this issue.

PMID- 18622145
TI  - [Skin and soft tissue infections: current therapeutic options].
AB  - In the present review, the authors focus on skin and soft tissue infections
      (SSTIs), a set of commonly observed pathologies which can present different
      features in terms of site and localization, clinical characteristics, and the
      aetiological agent responsible; their severity is related to the depth of the
      affected sites. After a brief introduction to the diverse classification criteria
      which are currently adopted by various authors, the aetiology and role of the
      most frequently occurring pathogen, Staphylococcus aureus, often methicillin
      resistant is discussed, as well as the possible therapeutic options. We first
      present the internationally recommended guidelines, and stress that SSTI
      management has to conform to different criteria, in accordance with the different
      clinical settings: mild infections require simple and cost-saving treatments
      while severe infections make timely and aggressive treatments mandatory. The
      review then reports the recent data concerning the efficacy of new antimicrobials
      for treating SSTIs. In particular, results observed with linezolid, tigecycline,
      and daptomycin are discussed.

PMID- 18622147
TI  - [Association between raised IL-8 serum levels and resistance to combined peg
      interferon plus ribavirin therapy in HCV+ active chronic hepatitis].
AB  - IL-8 serum levels were measured in a group of 44 patients affected with Chronic
      Active Hepatitis (CAH) HCV+ at the beginning and end of peg-interferon plus
      ribavirin combined therapy. IL-8 levels were compared with those measured in a
      group of healthy controls. The patients were treated for 12 months, and then
      followed up for 6 months after the end of the therapy. IL-8 serum levels were
      detected by ELISA at the beginning and end of the therapy, and then at the end of
      the follow-up. IL-8 serum levels were significantly more elevated (p<0.01) in CAH
      HCV+ patients than in the healthy controls. Furthermore, IL-8 serum levels in
      those patients who subsequently showed a sustained virological response to the
      therapy, declined on treatment and maintained lower levels than in those who did
      not respond to therapy. Serum IL-8 can be considered and proposed as a non
      invasive and predictive marker of response to combined PEG IFN alpha2b +
      Ribavirin in CAH HCV +.

PMID- 18622148
TI  - Low bone mineral density in institutionalized patients with HIV and psychiatric
      co-morbidity.
AB  - Osteoporosis occurs in HIV-infected patients as well as in common psychiatric
      conditions and causes significant morbidity. There are no published studies
      assessing bone mineral density (BMD) in institutionalized HIV patients with
      associated psychiatric disorders. We analyzed 51 subjects in a case control
      study: 17 HIV patients (males or pre-menopausal females) with psychiatric co
      morbidity and a long-term antipsychotic and antiretroviral therapy; and 34
      control healthy subjects, not infected with HIV, matched with patients by age and
      sex. The results show that the HIV group had significantly higher rates of
      pathological T-scores, as compared with the controls (71% vs. 9% p<0.001).
      Chronic mental illness may represent a possible important co-factor influencing
      BMD in HIV patients. We suggest that fracture risk should be carefully evaluated
      for institutionalized HIV patients with psychiatric co-morbidity.

PMID- 18622149
TI  - Inguinal lymphadenopathy due to Bartonella henselae.
AB  - The bacterium Bartonella henselae causes cat scratch disease, a self-limited
      zoonotic disease which is common among children and adolescents. The most typical
      clinical presentation is a regional lymphadenopathy that commonly involves only a
      single node of cervical and axillary lymph nodes. Inguinal localization is rarely
      described. We report a case of a 35-year-old Caucasian male complaining of a
      painless right inguinal mass and slight fever. A diagnosis of Bartonella henselae
      infection was made according to the histopathological exam of the excised mass,
      that showed an inflammatory state likely due to Bartonella, and to the titre of
      antibodies for this agent. Cat scratch disease can occur at any age and may also
      involve inguinal lymph nodes. Therefore it should always be included in the
      differential diagnosis of lymphadenopathy for adults. It is important that a
      meticulous personal history is obtained and that a specific serological test and
      pathological examination of the lesions are carried out. Often antibiotic
      treatment is not required because it is a benign disease and often resolves
      spontaneously.

PMID- 18622150
TI  - [Linezolid therapy for the treatment of nocardial infection: report of a case and
      review of the literature].
AB  - Treatment of Nocardia infections continues to be difficult, especially for
      central nervous system infections or disseminated diseases and when sustained by
      highly drug-resistant species such as Nocardia farcinica. Linezolid, the first
      oxazolidinone approved for clinical use, shows an excellent in vitro activity
      against all species of Nocardia, and achieves good central nervous system and
      lung concentrations. We describe the case of a patient with pulmonary nocardiosis
      and intolerance to trimethoprim/sulfamethoxazole successfully treated with
      linezolid, and review all the published cases of systemic nocardiosis treated
      with this agent. On the basis of the available evidence, linezolid appears an
      effective option for the treatment of nocardiosis.

PMID- 18622151
TI  - Immune thrombocytopenic purpura as a complication of Bartonella henselae
      infection.
AB  - Immune thrombocytopenic purpura is an infrequent yet well-recognized complication
      of viral infections, such as mumps, rubella, varicella, cytomegalovirus,
      parvovirus and infectious monunucleosis by Epstein-Barr virus. Some recent
      studies have described a possible association between Henoch-Schonlein purpura, a
      non-thrombocytopenic purpura, and seropositivity for Bartonella henselae, but in
      the literature only sporadic case reports have described a severe immune
      thrombocytopenic purpura as a complication of Bartonella henselae infection. We
      report a case of an immunocompetent child with clinical and serological evidence
      of Bartonella henselae infection presenting with purpura and cervical
      lymphoadenopathy and treated with intravenous immunoglobulin. The patient
      obtained a rapid and persistent increase in platelet count and a complete
      regression of purpura.

PMID- 18622152
TI  - [Reports on nine cases of spondylodiscitis].
AB  - Spondylodiscitis is an infection of the intervertebral disk and the adjacent
      vertebrae, with or without associated epidural or psoas abscesses. It is a
      serious disease both due to its long-term course and the possible outcomes. It is
      frequently caused by S. aureus and, in endemic areas, by Mycobacterium
      tuberculosis and Brucella spp. We describe 9 cases, from October 2004 to August
      2005, all spontaneous diseases occurring in adults (mean age 64 years). The site
      of infection was lumbar in 7, lumbar-sacral in 1 and dorsal in 1. None were
      associated to sepsis. The causative bacteria were known in 6 cases (1 BK, 1 S.
      aureus, 4 Brucella) and unknown in 3 cases. In all cases therapy was only
      medical. Significant circulation in Sicily of both Mycobacterium tuberculosis and
      Brucella spp. make those microorganisms the most frequent agents of
      spondylodiscitis.

PMID- 18622153
TI  - [Physicians and philosophers tackling Cupid's disease: combating syphilis in the
      18th century].
AB  - After the great fear caused by the rapid spread of syphilis in the 16th century
      (and the progressive contraction in the following century), the European
      political authorities had to tackle a disease that had become endemic. There was
      no solution in terms of treatment since the cause was unknown: the only
      precaution seemed to be the repression of such behaviour as prostitution, which
      seemed connected to the spread of Cupid's disease, as syphilis was called
      euphemistically in cultured circles. Medicine was powerless, and thinkers and
      philosophers helped the rulers with their ideas to develop laws to repress and
      reduce the incidence of the disease. In the 18th century, philosophers such as
      Ludovico Antonio Muratori and Peter Frank (founder of the Health Police), the
      priest Maria Gennaro Sarnelli, the libertine Bernard De Mandeville, the
      Neapolitan thinker Gaetano Filangeri, the founder of Congregazione della Carita
      Don Giulio Canali and the Abbot Antonio Genovesi contributed with their studies
      and sometimes works to focus attention on health problems in relation to syphilis
      prevention, even if repression remained the most widely adopted solution.

PMID- 18622155
TI  - The expanding universe of inflammatory bowel disease genetics.
AB  - PURPOSE OF REVIEW: Genetic factors play an important role in the pathogenesis of
      inflammatory bowel disease. In this review, we will provide an update on the
      rapid advances in the discovery of inflammatory bowel disease, primarily Crohn's
      disease, associated genes. RECENT FINDINGS: Seven recently published Crohn's
      disease genome-wide association studies have confirmed prior findings related to
      the nucleotide-binding oligomerization domain 2 (NOD2) gene and the IBD5 locus.
      In addition, 10 novel loci have been identified and well replicated. SUMMARY:
      Several promising associations between Crohn's disease and gene variants have
      been identified and replicated, the two most widely replicated being variants in
      the IL23R and ATG16L1 genes. These findings highlight and further support the
      importance of the immune system and its interactions with the intestinal
      microflora in the pathogenesis of inflammatory bowel disease.

PMID- 18622156
TI  - Host-bacteria homeostasis in the healthy and inflamed gut.
AB  - PURPOSE OF REVIEW: We are currently entering an exciting transition period from
      studying the molecular and cellular bases of the virulence of bacterial pathogens
      to deciphering the mechanisms of tolerance of the gut commensal flora. This
      review attempts to delineate the (sometimes thin) border between these two
      situations that are at the heart of understanding gut homeostasis and its
      possible rupture. RECENT FINDINGS: Essential issues are examined, such as
      metagenomic analysis of gut microbiota, the control of inflammation leading to
      tolerance, the molecular bases of regulation and rupture, and the way pathogens
      themselves regulate inflammation. SUMMARY: Breakthroughs in understanding how gut
      homeostasis can be established, maintained or disrupted in the presence of
      microbes should be sources of new therapeutic targets and drugs (i.e. anti
      inflammatory, immunomodulatory and anti-infectious molecules).

PMID- 18622157
TI  - Pathogenic agents in inflammatory bowel diseases.
AB  - PURPOSE OF REVIEW: Infectious agents are still thought to be involved in the
      origin of inflammatory bowel disease. The focus in recent years has been more on
      Mycobacterium avium subsp paratuberculosis, adherent-invasive Escherichia coli or
      yeasts. RECENT FINDINGS: A metaanalysis has shown a significant association of M.
      avium subsp paratuberculosis and Crohn's disease and a large randomized placebo
      controlled trial reported an absence of sustained beneficial effects of combined
      antibiotic therapy on remission of active Crohn's disease. Adherent-invasive E.
      coli adhere via type 1 pili to carcinoembryonic antigen-related cell adhesion
      molecule 6 (CEACAM6), abnormally expressed by intestinal epithelial cells in
      Crohn's disease patients. Both colonization of the ileal mucosa and stimulation
      of ileal epithelial cells by tumour necrosis factor-alpha induce overexpression
      of CEACAM6, leading to an amplification loop of colonization and inflammation.
      Anti-Saccharomyces cerevisiae mannan antibodies are the most prevalent serologic
      marker in Crohn's disease. Major oligomannose epitopes supporting antibody
      formation are expressed by Candida albicans in human tissues, suggesting that a
      loss of tolerance to C. albicans could lead to antibody formation in a subset of
      Crohn's disease patients who are genetically predisposed. SUMMARY: M. avium subsp
      paratuberculosis, adherent-invasive E. coli and Candida are good candidates for
      an infectious aetiology of Crohn's disease on the basis of genetic
      susceptibility, which relates to impaired function in the defence against
      intracellular bacteria.

PMID- 18622158
TI  - Innate immunity in inflammatory bowel disease: state of the art.
AB  - PURPOSE OF REVIEW: Gut is exposed to enteric bacteria and food antigens but
      maintains its homeostasis without the development of acute or chronic
      inflammation in normal situations. Abnormal innate immunity to enteric flora may
      develop into intestinal inflammation such as inflammatory bowel disease. This
      paper reviews recent studies on innate immunity in gut homeostasis and
      inflammation, identifying novel susceptible genes and clarifying the interaction
      between epithelial cells and immune cells such as intestinal macrophages and
      dendritic cells, as well as the interaction between NOD2 and toll-like receptor.
      RECENT FINDINGS: Crosstalk between epithelial cells and monocytic cells such as
      macrophages and dendritic cells plays an important role in gut homeostasis.
      Dysregulation of this crosstalk leads to decreased epithelial integrity and
      chronic intestinal inflammation. Macrophages and dendritic cells also regulate
      bacterial flora for the maintenance of intestinal homeostasis. Interleukin-23
      derived from these cells is a key cytokine in inflammatory bowel disease
      pathogenesis. Interactions between NOD2 and toll-like receptor signaling pathways
      may cause abnormal immune responses and decreased bacterial clearance. Genome
      wide scanning has identified innate immunity-related genes as inflammatory bowel
      disease susceptibility genes. SUMMARY: Recent studies on gut innate immunity in
      animal models have greatly advanced our knowledge of inflammatory bowel disease
      pathogenesis. For further progress, human studies and clarification of the
      functions of the identified susceptibility genes are needed.

PMID- 18622159
TI  - Adaptive immunity in inflammatory bowel disease: state of the art.
AB  - PURPOSE OF REVIEW: Adaptive immune mechanisms are inherently involved in the
      pathogenesis of inflammatory bowel disease. This review summarizes the main
      discoveries made in 2007 within this field. RECENT FINDINGS: CD4 T cells
      secreting interleukin-17 (T helper type 17) cells have emerged as a key effector
      population driving colitis in animal models previously associated with
      exaggerated T helper type 1 responses. With regard to T-regulatory cells, a novel
      suppressive cytokine (interleukin-35) and induction of apoptosis as a means to
      exert suppression have been identified. The importance of specific chemokine
      receptors and integrins in effector and T-regulatory cell function in colitis has
      been recognized. SUMMARY: An improved understanding of adaptive immune
      mechanisms, on which manifold genetic and environmental traits might converge,
      and which ultimately mediate intestinal inflammation in inflammatory bowel
      disease, holds promise for novel effective therapeutic intervention.

PMID- 18622160
TI  - Intestinal fibrosis in inflammatory bowel disease: progress in basic and clinical
      science.
AB  - PURPOSE OF REVIEW: Intestinal fibrosis is a potentially serious complication of
      inflammatory bowel disease and its pathophysiology is still unclear. This review
      will discuss recent developments relating to sources of fibroblasts in intestinal
      inflammation, mediators that modulate fibroblast activation and function, as well
      as new clinical, laboratory, endoscopic and radiological studies aimed at
      improving diagnosis and management of intestinal fibrosis in inflammatory bowel
      disease. RECENT FINDINGS: The fibroblast remains the central cell responsible for
      intestinal fibrosis in inflammatory bowel disease and transforming growth factor
      beta1 is still the most potent pro-fibrogenic cytokine. Novel mediators, however,
      are being identified that modulate fibroblast function, such as interleukin-13,
      interleukin-21, galectin-3, osteopontin, Wnt and toll-like receptor ligands, and
      anti-tumor necrosis factor-alpha agents. New fibroblast sources are being
      identified, such as fibrocytes, and new mechanisms of fibroblast generation, like
      epithelial- and endothelial-to-mesenchymal transition. Animal models of
      intestinal fibrosis are still few, but new ways to induce gut fibrosis are being
      explored. Serological markers indicating a clinically complicated course that
      includes intestinal fibrosis are promising and are being tested in adult and
      pediatric populations, particularly in Crohn's disease. Video capsule endoscopy,
      the Given Patency capsule, double balloon enteroscopy, and computed tomographic
      enteroscopy are some of the new modalities being developed to assess the risk and
      improve the diagnosis of intestinal fibrosis. Novel therapeutic approaches
      include endoscopic balloon dilatation with conventional and double balloon
      enteroscopy, and local injection of glucocorticoids and tumor necrosis factor
      alpha blockers, showing partial but encouraging success. SUMMARY: More studies
      are needed to improve knowledge of the pathophysiology of intestinal fibrosis if
      better preventive, diagnostic and therapeutic measures are to be expected in the
      near future.

PMID- 18622161
TI  - Therapy of ulcerative colitis: state of the art.
AB  - PURPOSE OF REVIEW: Advances in conventional therapy, novel targets and
      therapeutic goals are the highlights of treatment for ulcerative colitis in the
      last year. There have also been disappointments. This review summarizes the highs
      and lows, with an emphasis on strategy as opposed to seeking the newest treatment
      option. RECENT FINDINGS: In conventional therapy, once daily therapy for 5
      aminosalicylic acid is generally sufficient. Furthermore, a new 5-aminosalicylic
      acid (mesalamine MMX) has been released that effectively induces and maintains
      remission. There have been reappraisals of immunomodulators and further
      evaluation of (yes, now conventional!) infliximab for ulcerative colitis.
      Opportunistic infections, long-term outcomes and the burden of disease are being
      characterized. New therapeutic targets included an antibody against T cells (anti
      CD3), but trials on visilizumab for acute severe colitis have been suspended. T
      cell costimulation, phosphatidylcholine to promote barrier function, new anti
      tumour necrosis factor agents, B-cell (anti-CD20) depletion and complementary
      therapies represent new therapeutic horizons. International agreement is needed
      on activity indices, definitions of remission, therapeutic goals (including
      mucosal healing) and outcomes that matter to patients, so that trials can be
      compared. SUMMARY: Advances will take time to alter mainstream practice, but 2007
      2008 is the year of organized strategies, with European, American and British
      guidelines on ulcerative colitis published or in press. These should be the
      platform for better outcomes for patients.

PMID- 18622162
TI  - Biologic therapy in Crohn's disease: state of the art.
AB  - PURPOSE OF REVIEW: This review is intended to appraise the evolution and latest
      developments in treatment strategies and management of patients with Crohn's
      disease. RECENT FINDINGS: The last 24 months has further established the role of
      anti-tumor necrosis factor therapy in Crohn's disease with two new agents
      demonstrating efficacy in well designed randomized controlled trials.
      Furthermore, other important strategies have been identified including inhibition
      of leukocyte trafficking and blocking of interleukin-12 and 23. Along with the
      evolution in drug therapies there has been more extensive investigation on the
      best means to use these new agents. SUMMARY: Biologic therapy has changed and
      will continue to transform the way we treat patients with Crohn's disease.
      Treatment success has been redefined. The challenges will be to utilize these
      agents in the best algorithms possible to benefit not only short-term but also
      long-term outcomes.

PMID- 18622164
TI  - Advances in esophageal motor disorders.
AB  - PURPOSE OF REVIEW: Esophageal motor disorders, often leading to dysphagia and
      chest pain, continue to pose diagnostic and therapeutic problems. In the past 12
      months important new information regarding esophageal motor disorders was
      published. This information will be reviewed in this paper. RECENT FINDINGS: A
      number of studies have addressed the issue of heterogeneity in achalasia, the
      best defined esophageal motility disorder. The spastic esophageal motility
      disorders nutcracker esophagus and diffuse esophageal spasm may coexist with
      gastroesophageal reflux disease, which has consequences for the management of
      patients with these disorders. The entity labelled ineffective esophageal
      motility is associated with reflux esophagitis, but also with morbid obesity. For
      the detection of disordered transit caused by ineffective esophageal motility,
      application of intraluminal impedance monitoring in conjunction with manometry
      leads to improved diagnosis. New data on the effect of Nissen fundoplication on
      esophageal motility were published during the last year. SUMMARY: Recent
      knowledge on the heterogeneity of achalasia and the association of spastic
      esophageal motor disorders and ineffective motility with reflux disease will help
      the clinician in the management of patients with these disorders.

PMID- 18622165
TI  - Novel developments in esophageal vascular disorders.
AB  - PURPOSE OF REVIEW: Esophageal variceal bleeding is a life-threatening
      complication of liver cirrhosis. The aim of this review is to discuss the most
      important studies published in 2007 concerning diagnosis of esophageal varices,
      primary and secondary prophylaxis and treatment of variceal bleeding. RECENT
      FINDINGS: The specific areas reviewed are the noninvasive or minimally invasive
      diagnosis of oesophageal varices, prevention of the formation of varices and
      their progression from small to large, prevention of the first variceal
      hemorrhage, treatment of acute bleeding episodes and prevention of rebleeding,
      assessment of costs related to prophylaxis and treatment of variceal bleeding.
      Multidetector computed tomographic esophagography was found to identify the
      presence and grade the size of esophageal varices. Portal vein thrombosis was
      found to be an independent predictor of the aggravation of esophageal varices in
      patients with cirrhosis and hepatocellular carcinoma. The role of hepatic vein
      pressure gradient measurement in the prediction of decompensation of cirrhosis
      has been elucidated. SUMMARY: Relevant studies are reviewed on the diagnosis and
      the natural history of esophageal varices, prevention of their formation and
      growth, prevention of the first variceal bleed, use of hepatic vein pressure
      gradient to predict the evolution of portal hypertension and to estimate the
      response to pharmacological treatment, prediction of bleeding, treatment of
      variceal bleeding and prevention of rebleeding, and cost strategies.

PMID- 18622166
TI  - Scope of drug-induced, infectious and allergic esophageal injury.
AB  - PURPOSE OF REVIEW: The most common cause of esophageal injury is gastroesophageal
      reflux disease, however other less recognized causes may affect the esophagus. In
      this review we will focus on pill-induced esophageal injury, infections of the
      esophagus and eosinophilic esophagitis. RECENT FINDINGS: Esophageal infections
      are less frequent since HIV infection has become better controlled with antiviral
      therapies. The most emergent 'allergic' disease of the esophagus is eosinophilic
      esophagitis, which has become increasingly recognized in children and adults over
      the last decade. Eosinophilic esophagitis is a clinicopathologic disorder
      characterized by a dense esophageal eosinophilia generally occurring in
      association with upper gastrointestinal symptoms, primarily intermittent
      dysphagia, and refractory to proton pump inhibitor therapy. SUMMARY: Drug-induced
      esophageal injury remains underdiagnosed and should be better recognized.

PMID- 18622167
TI  - New developments in gastroesophageal reflux disease diagnosis and therapy.
AB  - PURPOSE OF REVIEW: Gastroesophageal reflux disease is a highly prevalent chronic
      condition in Western populations. It has a profound effect on our society in
      terms of economic cost and quality of life. There have been major advances in
      understanding of disease pathogenesis over the last few years which are
      summarized in this article. RECENT FINDINGS: With improved understanding of
      gastroesophageal reflux disease, newer developments in diagnostic techniques have
      evolved. The proton pump inhibitor test has been formally described as one of the
      initial diagnostic tests. Other new tests include multiple channel impedance
      monitoring, bilirubin reflux monitoring, Barostat measurements and intraluminal
      ultrasounds which, along with other newer technologies, are described in this
      review. SUMMARY: The mechanisms involved in the pathogenesis of gastroesophageal
      reflux disease are complex and multifactorial. The lower esophageal sphincter
      pressure, the motility of the esophageal body and the stomach, the composition of
      the reflux material and the sensitivity or resistance of the esophageal mucosa to
      the reflux material are important factors involved in the pathogenesis of disease
      related symptoms and lesions. Based on our improving understanding, novel
      diagnostic tools are available to improve investigation of the disease.

PMID- 18622168
TI  - The nonerosive reflux disease-gastroesophageal reflux disease controversy.
AB  - PURPOSE OF REVIEW: To analyse the concept of nonerosive reflux disease (NERD),
      examining its evolving definition and its relationship to reflux disease and
      functional gastrointestinal disorders. RECENT FINDINGS: The advent of the
      Montreal definition of gastroesophageal reflux disease (GERD) and the Rome III
      definition of functional upper gastrointestinal disorders has refined the concept
      of NERD. The high prevalence of GERD symptoms and the strong overlap between GERD
      and irritable bowel syndrome is due to the influence of NERD. Subtle differences
      exist between patterns of acid exposure in NERD and erosive disease on pH
      testing. Symptom generation in NERD may be influenced by altered mucosal
      permeability. Improvements in endoscopic technology demonstrate esophageal
      mucosal changes in NERD which are not seen in controls. There is a general
      acknowledgement that the inferior symptomatic response to acid suppression
      reported in NERD is attributable, at least in part, to contamination of study
      populations by patients with functional heartburn. SUMMARY: NERD is common and
      its definition continues to evolve. For the present, however, this should be
      considered to be heartburn with and without regurgitation due to gastroesophageal
      reflux in the absence of esophageal mucosal erosions. Future studies examining
      treatment response of GERD subgroups must exclude functional heartburn if NERD is
      to be properly understood.

PMID- 18622169
TI  - What's new in columnar lined esophagus (Barrett's metaplasia)?
AB  - PURPOSE OF REVIEW: The rising incidence of esophageal adenocarcinoma in the
      Western world has led to continued interest in its precursor lesion, Barrett's
      esophagus. This review endeavors to summarize the recent advances in our
      understanding of Barrett's esophagus with an emphasis on novel imaging techniques
      and endoscopic therapies. RECENT FINDINGS: There are indications that ethnic
      minorities such as blacks and Hispanics are at considerably lower risk for
      Barrett's esophagus (<2%) compared with whites. Central obesity rather than BMI
      could be a more important determinant of Barrett's metaplasia and neoplasia.
      Novel imaging techniques, in feasibility trials, have shown high accuracy for the
      detection of metaplasia and dysplasia. Finally, a much lower prevalence of
      concomitant occult invasive cancer among high-grade dysplasia patients undergoing
      esophagectomy and similar long-term survival in endoscopically versus surgically
      treated high-grade dysplasia patients has led to a shift in treatment algorithms
      favoring endoscopic therapy. SUMMARY: A better appreciation of risk factors that
      lead to Barrett's esophagus and its neoplastic progression may help in
      formulating early intervention strategies. The emergence of novel imaging
      modalities for early and accurate detection of dysplasia, combined with new
      therapies, may have a substantial impact in improving outcomes among Barrett's
      esophagus patients.

PMID- 18622170
TI  - Detection and endoscopic therapy of early esophageal adenocarcinoma.
AB  - PURPOSE OF REVIEW: This review summarizes recent progress on endoscopic diagnosis
      and treatment of esophageal high-grade intraepithelial neoplasia and early
      adenocarcinoma and critically analyzes the literature in the context of
      preexisting scientific data. RECENT FINDINGS: Narrow band imaging and computed
      virtual chromoendoscopy enhanced visualization of the mucosal morphology. The
      type of mucosal and capillary patterns seen on narrow band imaging predicted the
      presence of specialized intestinal metaplasia, high-grade intraepithelial
      neoplasia and early adenocarcinoma. Endocytoscopy lacked sufficient image quality
      for clinical use currently. Optical coherence tomography had the potential to
      diagnose specialized intestinal metaplasia and dysplasia. Photodynamic therapy
      produced long-term ablation of high-grade intraepithelial neoplasia and reduced
      cancer risk. Endoscopic radiofrequency ablation of Barrett's mucosa did not cause
      strictures and buried glandular mucosa. Localized and radical or complete
      circumferential endoscopic mucosal resections were effective and safe. SUMMARY:
      Virtual chromoendoscopy detected subtle mucosal lesions and facilitated targeted
      biopsies. Photodynamic therapy was effective in the long term. Endoscopic
      radiofrequency ablation appeared promising. Localized and radical or complete
      circumferential endoscopic mucosa resections were effective therapies.

PMID- 18622171
TI  - Staging and restaging of advanced esophageal cancer.
AB  - PURPOSE OF REVIEW: Esophageal cancer staging continues to evolve, especially for
      advanced cases. Computer tomography (CT) scan of the thorax and abdomen to detect
      metastatic disease, and endoscopic ultrasound with fine needle aspiration (EUS
      FNA) remain the preferred methods. Several recent studies have evaluated
      alternative methods for locoregional and distant disease detection and staging.
      RECENT FINDINGS: There seems to be emerging roles for fluorine-18
      fluorodeoxyglucose (FDG)-PET, laparoscopic staging, and high-resolution T2
      weighted MRI in esophageal cancer staging. Perfusion CT and FDG-PET and FDG
      PET/CT may have an emerging role in assessing response to neoadjuvant therapy.
      Restaging following neoadjuvant therapy remains suboptimal. A 50% or more
      reduction of tumor thickness by EUS postchemotherapy continues to be the best
      measure for tumor downstaging survival, while FDG-PET/CT may be more accurate
      than EUS-FNA and CT scan for predicting nodal status and complete responders
      after neoadjuvant therapy. Potential methylation analysis, digital image
      analysis, and fluorescence in-situ hybridization on EUS-FNA samples may increase
      the yield and prove to be better than routine cytology. SUMMARY: For advanced
      esophageal cancer, locoregional staging is best performed with EUS-FNA, with CT
      scan of the thorax and abdomen and FDG-PET, to detect metastatic disease. The
      role of EUS in restaging following neoadjuvant therapy remains controversial,
      with recent studies showing that FDG-PET/CT may be more accurate than EUS-FNA and
      CT scan for predicting nodal status and complete responders after neoadjuvant
      therapy.

PMID- 18622172
TI  - Treatment of locally advanced esophageal cancer with surgery and chemoradiation.
AB  - PURPOSE OF REVIEW: This article reviews developments in the treatment of locally
      advanced esophageal cancer with surgery and chemoradiation published in 2007.
      RECENT FINDINGS: Overall long-term survival is the same for patients after
      transhiatal or transthoracic esophagectomy. The pathology report of the resected
      specimen should contain information on lymph node status, such as size, location
      and lymph node ratio. If surgery is performed in patients with advanced
      esophageal cancer, there is small survival advantage if combined with neoadjuvant
      therapy, that is chemoradiation. Prognostic factors are a good performance
      status, a major response to chemoradiation and an early metabolic response with
      fluorine-18 fluorodeoxyglucose PET. Definitive chemoradiation may have similar
      results as combination treatment including surgery in selected patients with
      esophageal squamous cell cancer. Salvage surgery should be considered if
      definitive chemoradiation fails, provided that an R0 resection can be performed.
      Nutritional status is a prognostic factor in patients undergoing treatment of
      esophageal cancer. SUMMARY: In 2007, refinements of the nodal status in the
      tumor, node, metastasis system were proposed. Chemoradiation followed by surgery
      is increasingly being used in patients with advanced esophageal cancer. Evidence
      suggests that definitive chemoradiation could be a reliable treatment option in
      selected patients with esophageal squamous cell cancer.

PMID- 18622173
TI  - Bibliography. Current world literature. Inflammatory bowel disease.

PMID- 18622174
TI  - Effects of hypophysectomy on compulsive checking and cortical dendrites in an
      animal model of obsessive-compulsive disorder.
AB  - Hormones may modulate the symptoms of obsessive-compulsive disorder (OCD), but
      the evidence is equivocal and not consistent across studies, with findings of
      hormone-associated increases and decreases of symptoms. To assess whether a
      strong endocrine influence on OCD exists, the effects of hypophysectomy were
      examined in an animal model of OCD. The model involves repeated injections of the
      dopamine D2/D3 receptor agonist, quinpirole, to induce locomotor sensitization
      and compulsive checking behavior. Intact and hypophysectomized rats were
      administered quinpirole (0.5 mg/kg x 6, twice weekly) or saline and compulsive
      checking in a large open field was measured according to a standard protocol.
      Results showed that in hypophysectomized animals, the development of locomotor
      sensitization was attenuated but the expression of quinpirole-induced compulsive
      checking was full-blown. Analysis of Golgi-stained neurons showed changes in
      spine density in Cg3 and Par1 and increased branching of apical dendrites in Cg3.
      It is suggested that compulsive checking could be coupled with drug-induced
      increases in Cg3 dendritic branching and that changes in spine density may
      reflect a compensatory adjustment in dopamine-innervated regions. On the basis of
      the animal model findings, it is concluded that the presence of OCD checking
      compulsions is not dependent on pituitary axis hormones.

PMID- 18622175
TI  - Effects of alcohol on inhibitory processes.
AB  - Earlier work has shown that alcohol may have disinhibiting effects on behaviour.
      Two studies tested the effects of a moderate dose of alcohol (0.6 g/kg) versus
      placebo on tasks that evaluate inhibitory processes related to alcohol stimuli,
      in moderate-to-heavy social drinkers (student population). An inhibition of
      interference task, the Stroop task (ST; study 1), and an inhibition of a
      prepotent response task, the go/no-go task (GNG; study 2), were used. The effects
      of alcohol on working memory function were also examined. Participants preloaded
      with alcohol made more errors on the colour and alcohol ST than those preloaded
      with placebo. In the GNG task, responding to alcohol-related pictures was slower
      than responding to neutral pictures. When participants were required to switch
      responding from neutral to alcohol-related go stimuli, responding became slower;
      however, responding to alcohol go stimuli became faster as time progressed; no
      effect of alcohol was found. Alcohol had no effect, compared with placebo, on the
      working memory tasks. Therefore, a moderate dose of alcohol had restricted
      effects on inhibitory processes: only interference inhibition measured in the ST
      was affected. Although the data obtained with the GNG task did not show an effect
      of alcohol on response inhibition, increased latency of response in the presence
      of alcohol-related stimuli compared with neutral stimuli indicates that alcohol
      stimuli are more salient to social drinkers, attracting a greater amount of
      attention.

PMID- 18622176
TI  - Food restriction and streptozotocin treatment decrease 5-HT1A and 5-HT2A receptor
      mediated behavioral effects in rats.
AB  - Food restriction and hypoinsulinemia can affect the synthesis, turnover, and
      receptor function of serotonin (5-HT) in brain. This study explored the effects
      of food restriction and streptozotocin treatment on behavioral effects related to
      5-HT1A (+)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) and 5
      HT2A [(+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI)] receptor
      activation. Lower lip retraction and flat body posture (8-OH-DPAT) and head
      twitching (DOI) were measured in rats during free feeding, food restriction,
      after treatment with streptozotocin, and finally after insulin replacement. 8-OH
      DPAT induced lower lip retraction and flat body posture whereas DOI induced head
      twitching. One week of food restriction (10 g/day) decreased 8-OH-DPAT-induced
      lower lip retraction, 8-OH-DPAT-induced flat body posture, and DOI-induced head
      twitching. Subsequently, 1 week of free access to food restored sensitivity to 8
      OH-DPAT and DOI-induced behavioral effects. Finally, 1 week after streptozotocin,
      8-OH-DPAT-induced flat body posture and DOI-induced head twitching were markedly
      reduced whereas 8-OH-DPAT-induced lower lip retraction was unchanged. One week of
      insulin replacement restored sensitivity to 8-OH-DPAT and DOI-induced behavioral
      effects. These results show that modest food restriction or experimentally
      induced diabetes can profoundly affect sensitivity to drugs acting at 5-HT1A or 5
      HT2A receptors; these results could be relevant to understanding the comorbidity
      of depression and diabetes.

PMID- 18622177
TI  - Sensitivity to delta9-tetrahydrocannabinol is selectively enhanced in beta
      arrestin2 -/- mice.
AB  - Little is known about the roles of beta-arrestins in the regulation of brain CB1
      cannabinoid receptors. This study investigated the role of beta-arrestin2 in
      cannabinoid behavioral effects using beta-arrestin2 -/- mice and their wild-type
      counterparts. A variety of cannabinoid ligands from different chemical classes
      that exhibit a variety of efficacies for activation of CB1 receptors were
      investigated, including Delta-tetrahydrocannabinol, CP55940, methanandamide, JWH
      073, and O-1812. Delta-tetrahydrocannabinol produced both greater antinociception
      and greater decreases in body temperature in beta-arrestin2 -/- compared with
      beta-arrestin2 +/+ mice. No significant differences were, however, present in
      either assay for the other CB1 agonists. Antagonist radioligand binding indicated
      no difference in the density of cannabinoid CB1 receptors in the cerebellum,
      cortex, or hippocampus of beta-arrestin2 +/+ and -/- mice. These data demonstrate
      that beta-arrestin2 may regulate cannabinoid CB1 receptor sensitivity in an
      agonist-specific manner.

PMID- 18622178
TI  - Effects of central administration of gonadotropin-releasing hormone agonists and
      antagonist on elevated plus-maze and social interaction behavior in rats.
AB  - The correlation between neuronal mechanism of anxiety and neuroanatomic
      expression/neuromodulatory role of gonadotropin-releasing hormone (GnRH), points
      to a role of GnRH in the modulation of anxiety. Therefore, we investigated the
      influence of GnRH agonists and antagonist on the anxiety-like behavior of rats in
      the elevated plus-maze and social interaction tests. GnRH agonists, leuprolide
      [100 or 200 ng/rat, intracerebroventricularly (i.c.v.)] or 6-D-tryptophan
      luteinizing hormone-releasing hormone (400 ng/rat, i.c.v.), significantly
      increased percentage of open arms entries, time spent in open arms, and time
      spent in social interaction. The observed anxiolytic effect of these agents was
      comparable with diazepam (0.5-1.0 mg/kg, intraperitoneally). Treatment with a
      GnRH antagonist [pGlu-D-Phe-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2, (100 ng/rat,
      i.c.v.)], significantly reduced percentage of open arm indices and decreased time
      spent in social interaction, indicating an anxiogenic-like effect. Further,
      castrated rats exhibited anxiogenic-like behavior in these tests, which was
      significantly attenuated by leuprolide (200 ng/rat, i.c.v.) or 6-D-tryptophan
      luteinizing hormone-releasing hormone (400 ng/rat, i.c.v.), indicating the
      noninvolvement of peripheral sex hormone in their anxiolytic-like effect, at
      least in castrated rats. In conclusion, this study indicated a putative role of
      GnRH in the control of anxiety, and further adds to the importance of
      investigating the possible role of the hypothalamus-pituitary-gonadal axis in
      regulating the anxiety-related disorders arising out of hypothalamus-pituitary
      adrenal axis dysregulation.

PMID- 18622179
TI  - Gamma-hydroxybutyric acid in male and female cynomolgus monkeys trained to
      discriminate 1.0 or 2.0 g/kg ethanol.
AB  - Gamma-hydroxybutyric acid has been proposed as a pharmacotherapy for alcoholism
      in part based on similar discriminative stimulus effects as ethanol. To date,
      drug discrimination studies with gamma-hydroxybutyric acid and ethanol have
      exclusively used rodents or pigeons as subjects. To evaluate possible differences
      between species, sex, and route of administration, this study investigated the
      substitution of gamma-hydroxybutyric acid (intragastrically or intramuscularly)
      for ethanol 30 or 60 min after administration in male (n=6) and female (n=7)
      cynomolgus monkeys trained to discriminate 1.0 and 2.0 g/kg ethanol. At least one
      dose of gamma-hydroxybutyric acid completely or partially substituted for ethanol
      in three of the 13 monkeys tested, with each case occurring in female monkeys.
      Ethanol-appropriate responding did not increase with gamma-hydroxybutyric acid
      dose. Monkeys were more sensitive to the response rate decreasing effects of
      gamma-hydroxybutyric acid administered intramuscularly compared with
      intragastrically. The lack of gamma-hydroxybutyric acid substitution for ethanol
      suggests that these drugs have different receptor bases for discrimination.
      Furthermore, the data do not strongly support shared discriminative stimulus
      effects as the rationale for gamma-hydroxybutyric acid pharmacotherapy for
      alcoholism.

PMID- 18622180
TI  - Protective effects of extract of Coeloglossum viride var. bracteatum on ischemia
      induced neuronal death and cognitive impairment in rats.
AB  - Our earlier study demonstrated that Coeloglossum viride (L.) Hartm. var.
      bracteatum (Willd.) extract (CE) significantly improved the impaired memory in
      mice caused by permanent two-vessel occlusion. To investigate whether chronic
      treatment with CE could influence cerebral ischemia-induced neuronal and
      cognitive impairments, we examined the effects of CE on two different kinds of
      cerebral injury: transient middle cerebral artery occlusion model of focal
      cerebral ischemia; four-vessel occlusion model of transient global forebrain
      ischemia. CE treatment (5 mg/kg, orally) significantly reduced lesion volume, and
      improved the performance of passive avoidance and rotarod motor tasks in
      transient middle cerebral artery occlusion rats. In the four-vessel occlusion
      model, neuronal cell loss in CA1 of hippocampus was significantly decreased and
      the performance in the Morris water maze was significantly improved in rats
      administered CE. We conclude that treatment with CE attenuated learning and
      memory deficits, motor functional disability, and neuronal cell loss induced by
      global or focal cerebral ischemia. These results suggest that CE may be a
      potential candidate for the treatment of vascular dementia.

PMID- 18622181
TI  - Effects of age on susceptibility to the induction of depressive behavior and
      imipramine in rats.
AB  - Effects of age on depression vulnerability and antidepressant efficacy remain an
      important concern. Here, we show, by using a novel animal model of depressive
      behavior, that young rats (4 weeks old) are more vulnerable to the induction of
      depressive behavior than older ones (3, 6, and 14 months old). The induced
      depressive behavior in different ages of rats, however, was similarly sensitive
      to imipramine. A direct cerebroventricular administration of brain-derived
      neurotrophic factor was also sufficient to produce an antidepressant-like effect
      in the rats of different ages. These results suggest that although different ages
      of rats exhibit different sensitivity to the induction of depressive behavior,
      the induced depressive behavior may involve the same type of underlying abnormal
      neuropathophysiology in the brain and is sensitive to imipramine and brain
      derived neurotrophic factor treatment.

PMID- 18622182
TI  - Temporal horizons of cigarette satiety: determining the window of time over which
      recent smoking influences motivation to smoke.
AB  - One of the hallmarks of drug addiction is a limitation of the temporal horizon of
      events that affect the behavior of drug users. The purpose of this experiment was
      to examine the time period over which smoking was influenced by an earlier
      opportunity to smoke. Baseline sessions measured how much was smoked in a current
      opportunity when it was preceded by a 2-h wait time in which no smoking was
      allowed. After the baseline phase, we examined the effects of temporal distance
      when an earlier opportunity to smoke (upon completion of a fixed ratio 100)
      preceded current smoking (upon completion of a progressive ratio). Temporal
      distance between these two opportunities to smoke was varied from 0 to 120 min.
      We found that current smoking for the group was reduced from baseline levels when
      the temporal distance was 0 min. At temporal distances ranging from 30 to 90 min,
      the individual's smoking returned to levels that were similar to baseline.
      Breakpoints were also a function of earlier smoking, and latencies to first puff
      of the session followed a similar trend. These findings provide evidence of the
      limited temporal horizons related to smoking bouts of smokers and may provide a
      useful measure for metabolism differences across populations. In addition, we
      suggest that the quantitative description of satiety provided by our procedures
      may validate drug replacement therapies involved in cessation treatments.

PMID- 18622184
TI  - Matching law analysis of rats' alcohol self-administration in a free-operant
      choice procedure.
AB  - The generalized matching law quantitatively describes the relation between
      relative response allocation and relative reinforcement allocation in a choice
      situation and has accounted well for drug-maintained choice behavior. Earlier
      studies applying the generalized matching law to alcohol-maintained choice,
      however, have produced somewhat atypical findings (e.g. poor fits, negative
      sensitivity values). These findings may be the result of the procedures used in
      the earlier alcohol studies (e.g. two-bottle choice procedure, variations in
      relative concentration of alcohol, volume consumed as dependent variable). This
      experiment examined the applicability of the generalized matching law to alcohol
      self-administration using procedures more similar to those typically used with
      other reinforcers. A free-operant choice procedure arranging concurrent variable
      interval schedules of alcohol reinforcement was used to vary rates of alcohol
      deliveries produced by two response options. Results showed that the generalized
      matching law provided a good description of changes in the relative allocation of
      behavior with changes in the relative rate of alcohol delivery. Thus, the
      atypical results in earlier studies were likely a result of the procedures used.
      These results suggest that the parameters of the generalized matching law may
      provide useful quantitative measures of the impact biological and environmental
      variables on alcohol-associated choice behavior.

PMID- 18622183
TI  - Effects of white and infrared lighting on apomorphine-induced pecking in pigeons.
AB  - This experiment was concerned with the role of the environment in the production
      and form of apomorphine-induced pecking of pigeons. Earlier literature has
      suggested that the pecking occurs even when pigeons are placed in complete
      darkness, but there are no systematic or quantitative reports of such pecking.
      Six pigeons were tested with doses of 0.1, 0.3, and 1.0 mg/kg apomorphine. Tests
      were made in conditions of white and infrared light. The apparatus used novel
      force transduction measures that provided for both the detection of a peck as
      well as its peak forcefulness. At the lowest dose tested, apomorphine elicited
      pecking when the pigeon was placed in white light, but not when the dose was
      examined under infrared lighting. As the dose increased, however, pecking was
      observed regardless of lighting condition. No consistent differences were found
      in forcefulness of pecking as a function of lighting condition or dose. Though
      response output was seemingly unaffected by the lighting condition at higher
      doses, videotaped analysis revealed important changes in the formal
      characteristics of pecking. In white light, apomorphine elicited pecking at
      stimuli in the chamber (e.g. screw heads or the pigeon's own toes), whereas in
      infrared light pecking was directed at the floor directly in front of the pigeon.
      Such differences may be attributable to shifts in control to other stimulus
      modalities when vision is limited. Additionally, apomorphine may have direct
      effects on retinal dopamine function modulating the expression of pecking in the
      dark.

PMID- 18622185
TI  - Attenuation of anxiety-related behaviour after the antagonism of transient
      receptor potential vanilloid type 1 channels in the rat ventral hippocampus.
AB  - The neurochemical mechanisms supporting the role of the ventral hippocampus in
      anxiety are now under investigation. To address this issue, we examined whether
      the pharmacological blockade of transient receptor potential vanilloid type 1
      (TRPV1) channels in the ventral hippocampus would attenuate anxiety-related
      behaviour. Rats infused with the TRPV1 channel antagonist capsazepine (2.0 nmol)
      showed less inhibitory avoidance than controls in the elevated plus-maze test.
      This result indicates an anxiolytic-like effect, and suggests a role for TRPV1
      channels in regulating anxiety.

PMID- 18622186
TI  - Behavior selectively elicited by novel stimuli: modulation by the 5-HT1A agonist
      8-OHDPAT and antagonist WAY-100635.
AB  - The serotonergic system has a broad influence on behavior, but its specific
      contribution to novel object exploration remains to be examined. Toward this end,
      we assessed the impact of the 5-HT1A agonist, 8-OHDPAT (0.01-0.05 mg/kg) and the
      5-HT1A antagonist, WAY-100635 (0.01-0.05 mg/kg) on novel object exploration in a
      familiar open-field environment. 8-OHDPAT produced a dose-related inhibition of
      responding to the novel object, whereas, WAY-100635 treatment induced a dose
      related increase in the investigatory response to the novel object. Combined, the
      effects of WAY and 8-OHDPAT treatments were statistically indistinguishable from
      saline. In terms of locomotor activity, only the highest dose of 8-OHDPAT (0.05
      mg/kg) altered locomotor activity and the effect was inhibitory. These findings
      provide evidence for an involvement of the serotonergic system in the response to
      novel stimuli and indicate that this effect can be dissociated from effects on
      overall activity including locomotor, rearing and grooming behaviors.

PMID- 18622187
TI  - Relationship between response rates and measures of reinforcing strength using a
      choice procedure in monkeys.
AB  - Concurrent schedules of reinforcement are increasingly being used to investigate
      the reinforcing strength of abused drugs. A purported advantage of concurrent
      schedules is that the primary dependent measure, percentage of responses emitted
      on the drug-associated manipulandum, is independent of the rate-altering effects
      of drugs. Data supporting this hypothesis are, however, rarely presented, which
      was one goal of this study. In addition, we tested the hypothesis that drug
      induced decreases in response rates provides an additional index to characterize
      abuse liability of drugs. This study examined the relationship between response
      rate and response allocation (i.e. drug choice) when 3,4
      methylenedioxymethamphetamine (MDMA, 0.03-0.3 mg/kg/inj) or cocaine (0.003-0.1
      mg/kg/inj) was the alternative to food under concurrent fixed-ratio reinforcement
      schedules in rhesus (n=4) and cynomolgus (n=16) monkeys, respectively. Increasing
      doses of MDMA or cocaine resulted in increased drug choice and dose-dependent
      decreases in overall response rates. For both drugs, response rates on the drug
      associated lever were not affected by dose and were not different from saline.
      Furthermore, at most doses, rates of responding on the food-associated lever were
      significantly higher than response rates on the drug-associated lever. Finally,
      MDMA but not cocaine decreased food-reinforced responding, providing evidence for
      potential differences between the drugs. These results demonstrate that under
      concurrent food-drug reinforcement schedules, response rates on the drug
      associated lever are independent of measures of reinforcement, whereas
      disruptions in food-maintained responding may be inversely related to abuse
      liability.

PMID- 18622189
TI  - Restrictive eating disorders: ancient challenges, new solutions.

PMID- 18622190
TI  - Gynecomastia in adolescents.
AB  - PURPOSE OF REVIEW: Gynecomastia is a common finding in adolescent men. The
      primary care provider should feel equipped to thoroughly evaluate this condition
      and to differentiate physiologic from pathologic breast enlargement. The present
      review focuses on the epidemiology, pathogenesis, evaluation, and treatment of
      gynecomastia during adolescence. RECENT FINDINGS: While gynecomastia has long
      been attributed to an imbalance between estrogen and androgen concentrations,
      recent literature has begun to illuminate other potential mechanisms for breast
      development in adolescent men. Increased leptin levels, as well as human
      chorionic gonadotropin and luteinizing hormone receptors on male breast tissue,
      may play a role. Newer treatment strategies, such as the antiestrogen raloxifene,
      have shown promising results; however, further studies are needed to determine
      long-term efficacy. As a result of the limited pharmaceutical treatment options,
      many more adolescents are seeking surgical intervention. SUMMARY: Gynecomastia is
      frequently encountered in the primary care setting. During adolescence, male
      breast enlargement is most often benign and rarely represents a pathologic
      mechanism. Careful attention should be paid to both the breast and testicular
      examination. A detailed history should include an inquiry regarding the use of
      illicit substances, anabolic-androgenic steroids, herbal products, and
      medications. The impact of gynecomastia on the adolescent's mental health should
      be assessed. A workup for pathologic causes is rarely required. Reassurance
      remains the standard of care for physiologic gynecomastia.

PMID- 18622191
TI  - Controversies in contraception.
AB  - PURPOSE OF REVIEW: New research is constantly being published regarding hormonal
      contraceptives and bone health, migraine headaches, thrombosis risk,
      hypertension, weight gain, and obesity, as well as emergency contraception. At
      times, these studies can be clarifying, but they can also raise new controversies
      and questions. It is important for providers to be aware of the emerging issues
      regarding contraceptive care for adolescent patients. RECENT FINDINGS: Research
      suggests that Depo-Provera (depot medroxyprogesterone acetate; Pfizer, New York
      City, New York, USA) and, perhaps, low-dose oral contraceptive pills can have
      adverse effects on adolescent bone health, although the data demonstrating
      reversibility of bone loss after discontinuation of these contraceptives are
      reassuring. Additionally, estrogen-containing contraceptives pose risks for
      patients, including the onset of or exacerbation of migraine headaches, venous
      thromboembolism, and hypertension. Depo-Provera has been implicated in weight
      gain, especially in girls who are already overweight. Obesity may decrease the
      efficacy of some hormonal contraceptives. Finally, the mechanism of action of
      emergency contraception is still unknown, although studies continue to suggest
      that it has primarily preovulatory, not postovulatory, effects. SUMMARY:
      Adolescent health providers need to be aware of the new research and
      controversies in contraceptive care in order to counsel and care for patients
      effectively.

PMID- 18622192
TI  - Clinical practice guidelines for treating restrictive eating disorder patients
      during medical hospitalization.
AB  - PURPOSE OF REVIEW: Anorexia nervosa is a life-threatening complex psychiatric
      disorder that often requires patients to be medically hospitalized. In order to
      help provide consistent high-quality care to inpatients medically hospitalized
      for nutritional deficiency, a clinical practice guideline for these patients was
      created at Children's Hospital Boston. This paper reviews essential components of
      the clinical practice guideline for patients with restrictive eating disorders.
      RECENT FINDINGS: There is considerable variability in admission practices,
      inpatient treatment and discharge criteria for patients with anorexia nervosa.
      Weight restoration is one critical factor in treatment, and research suggests
      that some medical complications are reversible with weight restoration. Weight
      gain during hospitalization is associated with better short-term outcomes, which
      indicate patients are continuing toward recovery. However, patients must be
      closely monitored during nutritional rehabilitation to avoid complications.
      SUMMARY: The clinical practice guideline for patients with restrictive eating
      disorders outlines the care patients receive during the course of their
      hospitalization. The clinical practice guideline has been effective in helping
      patients to meet weight-gain goals. Clinical practice guideline outcome data
      could be used to compare protocols on a national level and help establish best
      practices for the inpatient medical treatment for these patients.

PMID- 18622193
TI  - Caring for incarcerated youth.
AB  - PURPOSE OF REVIEW: Incarcerated youth are an unusually high-risk cohort with
      numerous unmet medical and psychiatric needs. Frequently seen medical conditions
      including sexually transmitted diseases, pregnancy, and psychiatric illness are
      reviewed along with recommended standards of care for this population. RECENT
      FINDINGS: The recent realization that two-thirds of juvenile detainees have a
      psychiatric disorder has sparked renewed interest in screening and treating these
      high-risk adolescents. The push for increased identification and treatment has
      been prompted by the hypothesis that treating illness reduces recidivism and
      therefore improves individual and community public health. Although many
      facilities perform psychiatric and medical health screening within 24 hours of
      detention, there are many lacking areas. Examples include limited sexually
      transmitted disease, HIV and pregnancy testing; given the high rates of
      asymptomatic sexually transmitted disease infection, universal screening is
      essential. Also, interpretation of psychiatric screening tools by untrained
      individuals and utilization of results to incriminate juveniles are other problem
      areas. SUMMARY: Incarcerated adolescents' time in detention represents a rare
      opportunity to provide care to this underserved population. Full implementation
      of recommended screening and assessment protocols could greatly enhance
      individual as well as community health.

PMID- 18622194
TI  - Transition from pediatric to adult services: are we getting it right?
AB  - PURPOSE OF REVIEW: The transition of healthcare from pediatric to adult settings
      has become more significant over the past 20 years as the survival of young
      people with chronic illness and disability has increased and healthcare delivery
      has become more complex. This review examines the evidence from recent studies
      and position statements to determine the current issues relating to transition.
      RECENT FINDINGS: Although there are many examples of excellent transition
      processes, these are mostly confined to individual clinics (often subspecialist),
      with little evidence of hospital-wide or regional planning. The notion of
      transition to adult healthcare has now spread from its roots in adolescent
      medicine to influence many subspecialty areas of practice. However, it remains
      largely confined to a pediatric paradigm and risks becoming disconnected from the
      principles and practice of adolescent medicine from which it emerged. SUMMARY:
      More systematic investment in regional clinical service planning is indicated, as
      is investment in more systematic approaches to training both pediatric and adult
      healthcare providers around the importance of transition to adult healthcare.
      Collaboration is urged in relationship to clinical service developments, training
      and research initiatives.

PMID- 18622195
TI  - Myths and controversies in adolescent dermatology.

PMID- 18622196
TI  - An update on selected connective tissue diseases in adolescents.
AB  - PURPOSE OF REVIEW: This review highlights recent advances in our current
      understanding of several autoimmune disorders that affect adolescents. Systemic
      lupus erythematosus, juvenile dermatomyositis, and juvenile localized scleroderma
      stand out among the connective tissue diseases for their multiorgan involvement,
      significant potential morbidity, and the challenges of chronic treatment. RECENT
      FINDINGS: A better understanding of the pathogenesis of these diseases and new
      insights into the relationship between the immune dysregulation and clinical
      features has allowed for the development of novel therapies that are more
      efficacious and targeted than traditional therapies. SUMMARY: This article
      provides an update of the recent literature, highlighting advances that the
      general pediatrician should know in the care of adolescents with these diseases.

PMID- 18622197
TI  - New insights and therapies for teenage psoriasis.
AB  - PURPOSE OF REVIEW: Psoriasis is an important disorder in the adolescent
      population and has a tremendous physical and psychological impact on patients. It
      is important to understand the genetics, various clinical presentations,
      comorbidities, and treatment options associated with psoriasis. RECENT FINDINGS:
      The human leukocyte antigen-C gene likely contains a susceptibility locus for
      psoriasis. Cytokines interleukin-12 and interleukin-23 have been implicated in
      the pathogenesis of psoriasis as well. Psoriasis is likely associated with an
      increased risk of myocardial infarction, metabolic syndrome, Crohn's disease, and
      depression; it is difficult to assess the implications in the adolescent
      population. SUMMARY: Psoriasis is not rare in the adolescent population. It is
      important for physicians to be aware of the different clinical presentations as
      well as the spectrum of treatment options that are available.

PMID- 18622198
TI  - An update on childhood urticaria and angioedema.
AB  - PURPOSE OF REVIEW: The present review serves to address urticaria - both acute
      and chronic - as well as the differential diagnosis of urticarial syndromes in
      the pediatric population. We also wish to update the reader on progress in the
      pathophysiology, diagnosis and treatment of urticaria. RECENT FINDINGS: Acute and
      chronic urticaria represent syndromes caused by a variety of triggers. Recent
      literature continues to describe subtypes of urticaria that may be differentially
      responsive to particular therapies. Recent associations highlight the need to
      fully evaluate patients for allergic and infectious triggers of urticaria. It is
      important to distinguish idiopathic urticaria from related conditions such as
      anaphylaxis, systemic conditions and autoimmune urticaria. Although
      antihistamines remain a cornerstone of therapy, particular urticaria subtypes may
      also respond to novel therapies such as omalizumab. Chronic urticaria has a
      significant impact on a patient's quality of life. SUMMARY: Urticaria is a common
      condition. Our understanding of distinct urticaria subtypes differentially
      responsive to targeted therapies continues to increase. Due to the myriad of
      triggers that may cause urticaria, careful individualized patient assessment is
      necessary to exclude potential etiologies prior to a diagnosis of idiopathic
      urticaria.

PMID- 18622199
TI  - Adolescent hair loss.
AB  - PURPOSE OF REVIEW: Hair loss, or alopecia, may occur as a primary skin disorder
      or because of an underlying health problem. It may be upsetting to patients,
      particularly adolescents who are experiencing physical, emotional, and
      psychological transitions. Understanding the impact of alopecia is important for
      care providers who see adolescents. RECENT FINDINGS: The most common forms of
      alopecia in adolescence are telogen effluvium, androgenetic alopecia, and
      alopecia areata. Telogen effluvium may present suddenly or insidiously secondary
      to a variety of triggers. Androgenetic alopecia may begin in adolescence, and
      topical minoxidil is effective at retarding further hair loss. It may be a sign
      of underlying androgen excess, particularly polycystic ovary syndrome in women.
      Alopecia areata is less common, but may be distressing, especially if hair loss
      is extensive. Because treatments for alopecia are not curative, helping affected
      patients cope by offering support and nonpharmacologic techniques to help appear
      more like their peers should be part of care. SUMMARY: Physicians need to be
      skilled in evaluating the most common forms of alopecia presenting in adolescence
      and should be aware of potential treatments, including the value of psychosocial
      support.

PMID- 18622200
TI  - New insights into adolescent acne.
AB  - PURPOSE OF REVIEW: Acne vulgaris remains one of the most common conditions
      affecting adolescents. The pediatric practitioner is the first to evaluate
      adolescent acne, making familiarity with the condition and its management
      essential. This review covers some of the recent literature regarding acne to
      help practitioners stay current on the issues regarding this topic. RECENT
      FINDINGS: The pathogenesis of acne is multifactorial and complex, but recent
      advances in molecular genetics have provided additional information on the
      actions of Proprionibacterium acnes. Nutritional studies have reevaluated a
      possible role for diet and lifestyle factors in acne development. Many therapies
      are available to control acne and to limit associated scarring. Their appropriate
      use requires an understanding of not only the benefits but also the possible
      risks and adverse effects involved. Recent concerns regarding the use of
      antibiotics and isotretinoin will be addressed. SUMMARY: This study reviews the
      recent literature regarding teenage acne, focusing on pathogenesis, associations,
      and controversies and considerations in therapy.

PMID- 18622201
TI  - Human papillomavirus vaccine: recommendations, issues and controversies.
AB  - PURPOSE OF REVIEW: The human papillomavirus vaccine is now Food and Drug
      Administration-approved for girls and young women ages 9-26 years and Advisory
      Committee on Immunization Practices-recommended for girls ages 11-12 years of
      age. Several issues have shrouded its debut and continue to provide controversy
      that may hinder effective delivery of this vaccine to young people in
      industrialized as well as third world countries. RECENT FINDINGS: The
      quadrivalent and divalent vaccines are compared, particularly with respect to
      juvenile recurrent respiratory papillomatosis. Recommendations for administration
      are summarized. Immunization of men and cost effectiveness are discussed. Issues
      regarding compulsory vaccination and attitudes of parents about human
      papillomavirus vaccination are reviewed. SUMMARY: Studies of the human
      papillomavirus vaccine are very promising, showing excellent efficacy and very
      few adverse events. It remains to be determined if it will be licensed in the
      United States for use in boys and men. Some stumbling blocks to implementing the
      vaccine in the United States need to be addressed in order to gain widespread
      acceptance.

PMID- 18622202
TI  - Endocrinology and metabolism.

PMID- 18622203
TI  - Differentiating appropriate antidiuretic hormone secretion, inappropriate
      antidiuretic hormone secretion and cerebral salt wasting: the common, uncommon,
      and misnamed.
AB  - PURPOSE OF REVIEW: Causes of hyponatremia in children include the syndrome of
      appropriate antidiuretic hormone secretion, the syndrome of inappropriate
      antidiuretic hormone secretion and cerebral salt wasting. The purpose of this
      review is to distinguish these possibilities, focusing on cerebral salt wasting.
      RECENT FINDINGS: Most cases of hyponatremia in children are due to the syndrome
      of appropriate antidiuretic hormone secretion. The syndrome of inappropriate
      antidiuretic hormone secretion can be seen with neurological injury, pain and
      medication use. Recent studies suggest that cerebral salt wasting is a rare cause
      of hyponatremia. When cerebral salt wasting is diagnosed, it is often difficult
      to make a direct link with the central nervous system insult. SUMMARY: The
      clinical condition, assessment of extracellular fluid space volume status,
      measurement of urinary electrolytes and responses to infusion of saline solutions
      can distinguish between syndrome of appropriate antidiuretic hormone secretion,
      syndrome of inappropriate antidiuretic hormone secretion and cerebral salt
      wasting. The word 'cerebral' in 'cerebral salt wasting syndrome' can thus be
      inappropriate, conveying inaccurate causation.

PMID- 18622204
TI  - Physiological roles of 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6
      phosphate dehydrogenase.
AB  - PURPOSE OF REVIEW: Inactive cortisone is converted to active cortisol by the
      reductase activity of 11 beta-hydroxysteroid dehydrogenase type 1, which can thus
      increase glucocorticoid effects in target tissues. This paper reviews the
      functional role(s) of 11 beta-hydroxysteroid dehydrogenase type 1 and examines
      factors influencing its activity. RECENT FINDINGS: In obese humans, 11 beta
      hydroxysteroid dehydrogenase type 1 is relatively highly expressed in adipose
      tissue. In mice, overexpression of 11 beta-hydroxysteroid dehydrogenase type 1 in
      adipose or liver causes obesity or insulin resistance, respectively, whereas mice
      lacking 11 beta-hydroxysteroid dehydrogenase type 1 resist diet-induced obesity
      and are insulin-sensitive. Thus, 11 beta-hydroxysteroid dehydrogenase type 1 is a
      promising drug target for treating the metabolic syndrome and type 2 diabetes.
      Studies in vitro and in mutant mice demonstrate that the reductase activity of 11
      beta-hydroxysteroid dehydrogenase type 1 depends on reduced nicotinamide adenine
      dinucleotide phosphate synthesized within the endoplasmic reticulum by hexose-6
      phosphate dehydrogenase. Apparent cortisone reductase deficiency is characterized
      by androgen excess in women or children and decreased urinary excretion of
      cortisol metabolites. Although polymorphisms in the genes encoding 11 beta
      hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase were
      initially implicated in this condition, subsequent reports have not confirmed
      this. SUMMARY: Hexose-6-phosphate dehydrogenase and 11 beta-hydroxysteroid
      dehydrogenase type 1 may play important roles in the pathogenesis of obesity and
      metabolic syndrome. Although the importance of polymorphisms in the corresponding
      genes remains uncertain, rare mutations have not been ruled out.

PMID- 18622205
TI  - Genetic control of pubertal timing.
AB  - PURPOSE OF REVIEW: Puberty is an important developmental and life stage that
      leads to sexual maturation and reproductive capability. Although the physiology
      of puberty is similar among individuals, the timing of puberty is quite variable
      and affected by environmental and genetic influences. Identification of the
      responsible genetic factors will greatly enhance the understanding of the key
      components and the modulation of the hypothalamic-pituitary-gonadal axis. RECENT
      FINDINGS: Genetic analyses are increasingly elucidating the genetic basis of
      pathological abnormalities in pubertal timing, including causes of idiopathic
      hypogonadotropic hypogonadism and Kallmann syndrome. Ongoing studies are also
      investigating the genetic control of puberty in the general population, although
      no definitive association between genetic variants and variations in pubertal
      timing has been discovered so far. SUMMARY: This review summarizes recent
      advances regarding the genetic control of pubertal timing and presents areas for
      future investigation.

PMID- 18622206
TI  - Gynecomastia in prepubertal and pubertal men.
AB  - PURPOSE OF REVIEW: Gynecomastia is often benign, but it can be the sign of
      serious endocrine disease and the source of significant embarrassment and
      psychological stress. Understanding its pathogenesis is crucial to distinguish a
      normal developmental variant from pathological causes. RECENT FINDINGS: There is
      a growing list of potential causes of gynecomastia. Rare and unique case reports
      continue to supplement the literature to augment our understanding of this common
      physical finding. However, the exact basis for the pathogenesis of gynecomastia
      remains unknown. There appears to be a local imbalance between estrogen
      stimulation and the inhibitory action of androgens on breast tissue
      proliferation. Gynecomastia in a prepubertal boy is rare and should prompt an
      immediate evaluation for possible endocrine disorder. Pubertal gynecomastia, on
      the contrary, is common and usually physiological, with sympathetic reassurance
      and watchful waiting the mainstays of treatment. There is some evidence that
      early pharmacological intervention with antiestrogens may diminish persistent
      pubertal gynecomastia, but treatment with an aromatase inhibitor has not been
      shown to be more effective than placebo. SUMMARY: Treatment of gynecomastia is
      geared toward its specific cause. Currently, there are insufficient data to
      recommend medical therapy in children with idiopathic gynecomastia.

PMID- 18622207
TI  - Disorders of mitochondrial function.
AB  - PURPOSE OF REVIEW: Mitochondrial diseases are a major category of childhood
      illness that produce a wide variety of symptoms and multisystemic disorders. This
      review highlights recent clinically important developments in diagnostic
      evaluation and treatment of mitochondrial diseases. RECENT FINDINGS: Major
      advances have been made in understanding the genetic bases of mitochondrial
      diseases. Molecular defects have recently been reported in mitochondrial DNA
      maintenance, RNA translation and protein import and in mitochondrial fusion and
      fission, opening new areas of cell disorder. Diagnostic testing is struggling to
      keep pace with these fundamental discoveries. The diagnostic approach to children
      suspected of mitochondrial disease is rapidly evolving but few patients have a
      molecular diagnosis. A better notion of the prognosis of affected children is
      emerging from studies of long-term outcome. Some therapeutic successes are
      reported, such as in coenzyme Q deficiency conditions. SUMMARY: Mitochondrial
      diseases can present with signs in almost any organ. Well planned clinical
      evaluation is the key to successful diagnostic work-up of mitochondrial diseases.
      An approach is presented for further testing in specialized laboratories.
      Mitochondrial diseases can be caused by mutations in mitochondrial DNA or, more
      commonly in children, in nuclear genes. Mitochondrial DNA mutations pose special
      challenges for genetic counseling and prenatal diagnosis. Supportive treatment
      and avoidance of environmental stresses are important aspects of patient care.
      Specific treatment of mitochondrial diseases is in its infancy and is a major
      challenge for pediatric medicine.

PMID- 18622208
TI  - Update on universal childhood immunizations.
AB  - PURPOSE OF REVIEW: To provide an update of research findings and recommendations
      regarding immunizations. RECENT FINDINGS: New research has examined the efficacy
      of the 2007-2008 influenza vaccine, the transmission and incidence of human
      papillomavirus, the increased prevalence of pneumococcal serotypes not included
      in the 7-valent pneumococcal conjugate vaccine, the emergence of a drug-resistant
      strain of Streptococcus pneumoniae, febrile seizure rates following measles-mumps
      rubella-varicella vaccination, and the 2006 mumps outbreak in the American
      Midwest. The Food and Drug Administration has approved the expansion of live
      attenuated influenza virus vaccine and quadrivalent meningococcal conjugate
      vaccine for use in children no younger than 2 years of age. The Advisory
      Committee on Immunization Practices now recommends immunization with quadrivalent
      meningococcal conjugate vaccine for all previously unvaccinated 11-18-year-old
      children and has revised its recommendations for Streptococcus pneumoniae catch
      up vaccinations. The Advisory Committee on Immunization Practices no longer
      expresses a preference for the use of the combination measles-mumps-rubella
      varicella vaccine over separate measles-mumps-rubella and varicella
      administration. Because of a notable recall of Haemophilus influenzae type B
      vaccines by Merck & Co Inc, Whitehouse Station, New Jersey, USA, the Advisory
      Committee on Immunization Practices recommends that pediatric providers conserve
      available Haemophilus influenzae type B vaccines by delaying the administration
      of the booster dose of the vaccine in healthy children. SUMMARY: New vaccine
      recommendations continue to be made, and research continues on infectious
      diseases, vaccine safety, and vaccine efficacy.

PMID- 18622209
TI  - Case report: thyroid hormone resistance and its therapeutic challenges.
AB  - Thyroid hormone resistance occurs when a genetic mutation in the thyroid hormone
      receptor leads to reduced hormone binding affinity; the concentration of free
      thyroid hormone in the circulation is inversely correlated with the hormone
      binding affinity of the mutant receptor. Thyroid hormone resistance mutations are
      associated with a wide variety of phenotypes and subsequent treatment challenges.
      Among the more common symptoms are hyperactivity, emotional lability, a below
      average intelligence quotient, and short stature. We report here a patient who
      presented with thyroid hormone resistance at an early age, providing an
      opportunity to optimize her overall growth and development. We review the limited
      information currently available in the literature addressing the treatment of
      thyroid hormone resistance in children and describe the approach used to
      determine the treatment plan in this young child.

PMID- 18622210
TI  - Bibliography. Current world literature. Adolescent medicine.

PMID- 18622211
TI  - A penny for your thoughts.

PMID- 18622212
TI  - Kidney disease: latest offering on NIHSeniorHealth.

PMID- 18622213
TI  - Coronary artery plaque imaging device cleared by FDA.

PMID- 18622214
TI  - Osteoporosis monograph now available.

PMID- 18622215
TI  - Home Health Quality Improvement National Campaign: the journey and potential
      impact on clinical practice.
AB  - Home health agencies are in a position to respond to patient and healthcare
      system needs by implementing strategies targeted at reducing avoidable
      hospitalizations. Many different interventions exist that home care agencies can
      use in achieving the national goal to reduce avoidable acute care
      hospitalizations. This article provides an overview of the Home Health Quality
      Improvement (HHQI) National Campaign and the efforts directed toward this
      initiative. This overview explains the 4 best practices explored in depth by the
      campaign participants.

PMID- 18622216
TI  - Research on reducing avoidable hospitalizations.

PMID- 18622217
TI  - Ergonomics for home care providers.

PMID- 18622219
TI  - Insulin management: a guide for the home health nurse.
AB  - The number of Americans with diabetes mellitus (diabetes) has skyrocketed in the
      past 2 decades. An estimated 21 million Americans have the disease, and
      approximately 6 million additional people are unaware that they even have
      diabetes (National Diabetes Educational Program [NDEP] Fact Sheet, 2007). Among
      all the developed nations on the globe, the United States leads the world in
      cases of diabetes, 90% of which are type 2 diabetes (Kitis & Emirogluk, 2006;
      National Diabetes Fact Sheet, 2005). Unfortunately, these numbers are expected to
      climb even higher.

PMID- 18622221
TI  - Deactivation of automatic implantable cardioverter-defibrillators in hospice and
      home care patients at the end of life.
AB  - For patients at the end of life, active automatic implantable cardioverter
      defibrillators (AICDs) may no longer achieve the treatment goals present at the
      time of implantation. It is possible to deactivate AICDs in patients with
      terminal and life-limiting diagnoses, thereby preventing the pain and distress of
      nontherapeutic discharge. This article presents a moral argument for the right of
      such patients to have their AICDs deactivated. It then explains that hospice and
      home care agencies have an obligation to address AICD deactivation at a policy
      level and offers recommendations for doing so.

PMID- 18622222
TI  - The reality of rehabilitation at home.

PMID- 18622223
TI  - European Society of Hypertension guidelines for blood pressure monitoring at
      home: a summary report of the Second International Consensus Conference on Home
      Blood Pressure Monitoring.
AB  - This document summarizes the available evidence and provides recommendations on
      the use of home blood pressure monitoring in clinical practice and in research.
      It updates the previous recommendations on the same topic issued in year 2000.
      The main topics addressed include the methodology of home blood pressure
      monitoring, its diagnostic and therapeutic thresholds, its clinical applications
      in hypertension, with specific reference to special populations, and its
      applications in research. The final section deals with the problems related to
      the implementation of these recommendations in clinical practice.

PMID- 18622224
TI  - Influencing the natural history of hypertension: is it the blood pressure
      achieved, the drug, or the drug dose?

PMID- 18622225
TI  - Influencing the natural history of hypertension: it is the blood pressure
      achieved more than the drug.

PMID- 18622226
TI  - Out-of-office blood pressure measurement in children and adolescents.

PMID- 18622227
TI  - Office and out of office heart rate measurements: which clinical value?

PMID- 18622228
TI  - Flow-mediated dilatation as a biomarker for cardiovascular risk in hypertension.

PMID- 18622229
TI  - Size matters?

PMID- 18622230
TI  - Antihypertensive treatment and cognitive function: another tempest in a P pot?

PMID- 18622231
TI  - Simvastatin, an inhibitor of epithelial-to-mesenchymal transition in experimental
      atherosclerotic renovascular disease?

PMID- 18622232
TI  - Diagnosis of hypertension in children and adolescents based on home versus
      ambulatory blood pressure monitoring.
AB  - OBJECTIVE: To investigate the usefulness of home blood pressure measurements in
      comparison with ambulatory monitoring in the diagnosis of sustained, white-coat
      hypertension and masked hypertension in children and adolescents. SUBJECTS AND
      METHODS: One hundred and two subjects, referred for elevated blood pressure, were
      assessed with clinic (two visits), home (6 days) and awake ambulatory blood
      pressure measurements [64 boys, mean age 12.8 +/- 2.9 (SD) years, range 6-18
      years]. RESULTS: Office hypertension was diagnosed in 38 subjects, ambulatory
      hypertension in 31 and home hypertension in 23 (P = 0.07). On the basis of clinic
      and ambulatory blood pressure, 52% of subjects were normotensive, 20%
      hypertensive, 18% had white-coat hypertension and 11% masked hypertension,
      whereas on the basis of clinic and home blood pressure, 55, 15, 23 and 8%,
      respectively. There was an agreement between ambulatory and home blood pressure
      in the diagnosis of hypertension in 82 cases (80%). When a 5-mmHg gray zone of
      diagnostic uncertainty was applied above and below the diagnostic thresholds,
      there were only eight cases with clinically important disagreement. By taking
      ambulatory blood pressure as the reference method for the diagnosis of
      hypertension, the sensitivity, specificity and positive and negative predictive
      values of home blood pressure were 55, 92, 74 and 82%, respectively, for the
      diagnosis of white-coat hypertension 89, 92, 70 and 98%, respectively, and for
      masked hypertension 36, 96, 50 and 93%, respectively. CONCLUSION: In children and
      adolescents, there is a reasonable agreement between home and ambulatory blood
      pressure measurements as diagnostic methods in hypertension. Home blood pressure
      appears to be a useful diagnostic test in this population, particularly for the
      detection of white-coat hypertension.

PMID- 18622233
TI  - Usefulness of waist circumference for the identification of childhood
      hypertension.
AB  - OBJECTIVE: To investigate the ability of BMI and waist circumference, single and
      combined, in identifying children who are at risk of hypertension and in
      influencing absolute blood pressure values. METHODS: The body weight, height,
      waist circumference and blood pressure of 4177 5-11-year-old school children
      [2005 (48%) girls] were collected. Elevated blood pressure was defined if either
      systolic or diastolic blood pressure values or both were more than the 95th
      percentile according to sex, age and height (US normative blood pressure tables).
      Overweight and obese children were defined according to International Obesity
      Task Force BMI cut-offs. RESULTS: The prevalence of hypertension was 4.1% and
      increased together with weight class: 1.4% (n = 42/3076) in normal weight, 7.1%
      (n = 59/827) in overweight and 25% (n = 69/274) in obese (P < 0.001). Only BMI
      and waist circumference showed a remarkable ability to discriminate hypertensive
      children (areas under receiver operating characteristic curves, 0.84 and 0.76,
      respectively). The multivariate analysis showed that z-scores for both BMI and
      waist circumference were significantly related to the risk of hypertension with
      odds ratios of 3.59 (95% confidence interval, 2.55, 5.06) and 1.20 (95%
      confidence interval, 1.04, 1.39), respectively, after adjusting for sex and age.
      When the weight class was included in the multivariate analysis, waist
      circumference retained its ability to identify hypertensive children only in the
      obese class (odds ratio, 1.44; 95% confidence interval, 1.21, 1.72; P < 0.01).
      When considering blood pressure as a continuous variable, both weight class and
      waist circumference showed a significant effect on systolic and diastolic blood
      pressure absolute values (P < 0.01). The effect of waist circumference on blood
      pressure values was maintained even when corrected for BMI. CONCLUSION: High
      blood pressure is strongly associated with excess weight. Waist circumference
      improves the ability of BMI to identify hypertension in obese children. Waist
      circumference is related to absolute blood pressure values in all weight classes.

PMID- 18622234
TI  - Predictive value of ambulatory heart rate in the Japanese general population: the
      Ohasama study.
AB  - BACKGROUND: Resting heart rate can predict cardiovascular disease mortality or
      all-cause mortality. Because of the effect of the alert reaction, heart rates
      measured out-of-office should have better predictive power than those obtained at
      clinics. However, only a few studies have described the relationship between
      heart rate measured by ambulatory blood pressure monitoring devices and
      cardiovascular disease prediction. METHODS: We studied 1444 individuals from the
      Japanese general population who did not have a history of cardiovascular diseases
      including arrhythmia. We used multiple adjusted Cox proportional hazards to
      calculate the mortality risk of daytime heart rate, night-time heart rate, and
      the day-night heart rate dip ratio [day-night heart rate dip ratio = (daytime
      heart rate--night-time heart rate)/daytime heart rate x 100]. RESULTS: After 12
      years of follow-up, 101, 195, and 296 participants died due to cardiovascular
      diseases, noncardiovascular diseases, and all causes, respectively. As shown by
      others, neither daytime nor night-time heart rate predicted cardiovascular
      disease mortality, whereas both predicted noncardiovascular disease mortality.
      The day-night heart rate dip ratio was significantly related to all-cause
      mortality. When night-time heart rate and day-night heart rate dip ratio were
      simultaneously included into the same Cox model, only night-time heart rate
      significantly and independently predicted all-cause mortality (relative hazard
      per 10 bpm increase = 1.29, 95% confidence interval, 1.07-1.54). CONCLUSION:
      Night-time heart rate value seems to have the most important predictor of all
      cause mortality among ambulatory heart rate parameters in this population.

PMID- 18622235
TI  - Further evidence for linkage of familial hyperaldosteronism type II at chromosome
      7p22 in Italian as well as Australian and South American families.
AB  - BACKGROUND: Familial hyperaldosteronism type II is a hereditary form of primary
      aldosteronism not attributable to the hybrid CYP11B1/CYP11B2 mutation that causes
      glucocorticoid remediable aldosteronism (or familial hyperaldosteronism type I).
      Although genetic defect(s) underlying familial hyperaldosteronism type II have
      not yet been elucidated, linkage to chromosome 7p22 was previously reported in
      two Australian families and a South American family with familial
      hyperaldosteronism type II. OBJECTIVE: To seek evidence of linkage to chromosome
      7p22 in two Italian families with familial hyperaldosteronism type II based on
      markers that have already yielded evidence of linkage in one South American and
      two Australian familial hyperaldosteronism type II families and to assess the
      combined multipoint logarithm of odds score in these five families (two
      Australian, two Italian, and one South American). METHODS: Primary aldosteronism
      was diagnosed or excluded using widely accepted clinical and biochemical
      criteria. Genotypes of affected and unaffected Italian patients from two families
      were analysed using seven closely spaced microsatellite markers at 7p22, and
      multipoint logarithm of odds scores were calculated to assess linkage with
      familial hyperaldosteronism type II. RESULTS: All known affected individuals
      (four and two, respectively) from each of two Italian families shared identical
      haplotypes for the seven markers, consistent with linkage of the disease locus
      with the 7p22 region. The combined multipoint logarithm of odds score for five
      families showing linkage at 7p22 was highly significant at 5.22 (theta = 0) for
      markers D7S462 and D7S517. CONCLUSION: Linkage in two Italian families makes this
      the third geographical area to show linkage of familial hyperaldosteronism type
      II at 7p22, emphasizing the likely importance of this locus in identifying the
      causative mutation.

PMID- 18622236
TI  - Job strain, job demands and adrenergic beta1-receptor-polymorphism: a possible
      interaction affecting blood pressure in men.
AB  - BACKGROUND: Job strain and the Arg389Gly polymorphism in the adrenergic beta1
      receptor gene have been linked to hypertension. We aimed to study whether there
      is an interaction between the Arg389Gly polymorphism and job strain and its
      components (job demand and decision latitude) in relation to blood pressure.
      METHODS: From the Malmo Diet and Cancer population cohort, 6095 individuals were
      randomly selected to be followed regarding cardiovascular risk factors. From this
      group, employed individuals with baseline data regarding work characteristics
      were included (1338 men and 1707 women). Determination of adrenergic beta1
      receptor Arg389Gly polymorphism was possible in 1271 men and 1601 women, and
      these individuals formed the study group. RESULTS: Men with the combination of
      Arg389Arg and job strain were more often on antihypertensive medication (P =
      0.04), whereas blood pressure was not significantly higher, in comparison with
      those without both of these two factors. The interaction term genotype x job
      strain was borderline significant for systolic blood pressure (P = 0.07) after
      adjustments for age, country of birth, and job status. The demand score showed
      significant interaction in men with genotype (P = 0.01 for systolic blood
      pressure and P = 0.009 for diastolic blood pressure) after adjustments for age,
      country of birth, job status, antihypertensive treatment, and BMI. Men with the
      Gly389 allele had lower blood pressure with increasing demand score (P = 0.001),
      whereas men homozygous for the Arg389 allele had lower blood pressure with
      increasing latitude score (P = 0.03). In women, those with job strain tended to
      have higher blood pressure than those without job strain, among carriers of
      Arg389Arg and Arg389Gly genotype. CONCLUSION: Men with job strain and the
      Arg389Arg polymorphism were more often on antihypertensive treatment than other
      men. Significant interactions between the Arg389Gly polymorphism and aspects of
      job stress are described, but the absolute blood pressure differences are small.
      Considering the commonness of the polymorphism, stress, and hypertension further
      studies are indicated.

PMID- 18622237
TI  - Y2 receptor gene variants reduce the risk of hypertension in obese children and
      adolescents.
AB  - OBJECTIVE: To verify whether peptide YY (PYY) and its Y2 receptor (Y2R) gene
      variants can be associated with obesity or hypertension or both in a cohort of
      obese children and adolescents. PATIENTS AND METHODS: Two hundred and twenty-nine
      obese children (105 girls, mean z-score BMI 5.1 +/- 2.4; mean age 10.5 +/- 2.9
      years) and 250 age and sex-matched lean controls (130 women, mean z-score BMI 0.5
      +/- 1.1; mean age 10.3 +/- 2.8) were enrolled in the study. Height, weight, BMI,
      waist circumference and 24-h systolic and diastolic blood pressure were measured.
      Night-time, day-time and 24-h systolic and diastolic blood pressures were
      evaluated by 24 h ambulatory blood pressure measurement, and appropriate standard
      deviation scores according to sex, age and height were calculated. Molecular
      screening of the PYY and Y2R genes was performed. RESULTS: No new mutations were
      found. We observed three previously described polymorphisms: G767C on PYY and
      T585C and T936C on Y2R. An association study was carried out in obese patients.
      No associations were found between the PYY genotypes and the studied phenotypes.
      The Y2R gene variants, T585C and T936C, which are in almost complete linkage
      disequilibrium, were found to be associated with night-time, day-time and 24-h
      systolic and diastolic blood pressures. In particular, subject homozygotes for
      the T allele showed lower systolic and diastolic blood pressure values compared
      with the other genotypes. Moreover, obese children homozygous for the T585 allele
      showed a lower risk of developing hypertension than patients carrying the CC and
      CT genotypes (chi 6.9; df = 1, P = 0.03; odds ratio = 0.5, 95% confidence
      interval: 0.27-0.88). CONCLUSION: Our results suggest that Y2R gene variants are
      involved in blood pressure regulation in obese children and adolescents.

PMID- 18622239
TI  - Long-term risk of diabetes, hypertension and left ventricular hypertrophy
      associated with the metabolic syndrome in a general population.
AB  - OBJECTIVES: Metabolic syndrome is accompanied by an increased risk of developing
      diabetes mellitus. Limited or no evidence exists on whether and to what extent
      metabolic syndrome increases the risk of developing office hypertension, daily
      life hypertension and left ventricular hypertrophy. METHODS: In 1412 individuals
      representative of the population of Monza, plasma glucose, office, home and
      ambulatory blood pressure, and echocardiographic left ventricular mass index were
      measured between 1990 and 1992 and 10 years later. New onset diabetes mellitus,
      new onset office, home and ambulatory hypertension as well as new onset left
      ventricular hypertrophy were assessed in individuals with and without metabolic
      syndrome (Adult Treatment Panel criteria) at the first examination. RESULTS: New
      onset diabetes mellitus, hypertension and left ventricular hypertrophy were all
      much more frequent in individuals with metabolic syndrome than in those without.
      In patients with metabolic syndrome, the adjusted risk of new onset diabetes
      mellitus was five to six times greater (P < 0.001), that of new onset office,
      home or ambulatory hypertension 3.5, 2.9 and 3.2 times greater (P < 0.001),
      respectively, and that of new onset left ventricular hypertrophy 2.6 times
      greater (P < 0.001). The most important predictors of new onset diabetes
      mellitus, hypertension and left ventricular hypertrophy were the baseline blood
      glucose, blood pressure and left ventricular mass index, respectively, with an
      independent contribution, in each condition, from other metabolic syndrome
      components. The metabolic syndrome as such did not have an additional predictive
      value. CONCLUSION: In the general population, metabolic syndrome is associated
      with a marked increase in the risk not only of new onset diabetes mellitus but
      also of new onset office and daily-life hypertension, and left ventricular
      hypertrophy. This may account for the increased rate of cardiovascular morbidity
      and mortality exhibited with this condition in long-term studies.

PMID- 18622238
TI  - Angiotensin receptor blockers improve insulin signaling and prevent microvascular
      rarefaction in the skeletal muscle of spontaneously hypertensive rats.
AB  - OBJECTIVE: Spontaneously hypertensive rats are an example of an animal model of
      genetic hypertension with insulin resistance. The aim of this study was to
      investigate insulin signaling in the heart and in the skeletal muscle of
      spontaneously hypertensive rats, as well as to evaluate the effects of renin
      angiotensin system blockade. DESIGN AND METHODS: We investigated eight untreated
      spontaneously hypertensive rats of 12 weeks of age and eight age-matched
      normotensive Wistar-Kyoto controls. In addition, eight spontaneously hypertensive
      rats were treated for 8 weeks with the angiotensin receptor blocker olmesartan,
      and eight spontaneously hypertensive rats with the angiotensin-converting enzyme
      inhibitor enalapril. The heart and a skeletal muscle (quadriceps femoris) were
      promptly dissected and frozen. Insulin signaling was evaluated by Western blot
      analysis of involved proteins; in addition, microvessel density was indirectly
      evaluated by immunohistochemistry. RESULTS: Blood pressure values were normalized
      by both olmesartan and enalapril. In the heart, no statistically significant
      difference in the expression of proteins involved in insulin signaling was
      observed between untreated spontaneously hypertensive rats and Wistar-Kyoto
      controls. On the contrary, in the skeletal muscle of untreated spontaneously
      hypertensive rats, we noted a significant reduction of insulin receptors, of
      insulin-receptor substrate-1, and of phosphorylated-mammalian target of
      rapamycin. The treatment with olmesartan normalized insulin signaling, including
      expression of glucose transporter-4, whereas the treatment with enalapril was
      ineffective for the insulin receptor and less effective than olmesartan on the
      insulin-receptor substrate-1, phosphorylated-mammalian target of rapamycin and
      glucose transporter-4. There was a significant reduction in microvessel density
      in the skeletal muscle of spontaneously hypertensive rats compared with Wistar
      Kyoto controls, and this was completely prevented by both olmesartan and
      enalapril. CONCLUSION: These results suggest that changes in insulin signaling
      occur in the skeletal muscle but not in the heart of untreated spontaneously
      hypertensive rats. In the skeletal muscle, insulin signaling was restored by
      olmesartan, whereas enalapril was less effective. Effective antihypertensive
      treatment with olmesartan or enalapril was associated with prevention of
      microvascular rarefaction.

PMID- 18622240
TI  - Prognostic role of flow-mediated dilatation of the brachial artery in
      hypertensive patients.
AB  - BACKGROUND: The prognostic role of endothelial dysfunction, as evaluated by flow
      mediated vasodilatation of the brachial artery, has been demonstrated in patients
      at very high risk. We aimed to investigate whether flow-mediated vasodilatation
      predicts cardiovascular events in uncomplicated hypertensive patients. METHODS
      AND RESULTS: A total of 172 prospectively identified uncomplicated hypertensive
      patients (age 56 +/- 8 years, 41% women, 48 with diabetes mellitus type 2) were
      studied. At baseline all patients were untreated and underwent baseline standard
      laboratory examination. A standard echocardiogram was performed for the
      evaluation of left ventricular anatomy and function and patients with systolic
      dysfunction or left ventricular wall motion abnormalities were excluded.
      Endothelial function was measured as flow-mediated vasodilatation of the brachial
      artery using high-resolution ultrasound. Patients were followed for 95 +/- 37
      months (range 2-136 months). A first nonfatal or fatal cardiovascular event
      occurred in 32 patients. The incidence of cardiovascular events was 1.4 and 3.1
      per 100 patient-years in patients with a flow-mediated vasodilatation below and
      above the median value (4.7%), respectively (P < 0.005 by the log-rank test). In
      Cox analysis, controlling for age, sex, glycemia, cholesterol, smoking, BMI,
      systolic and diastolic blood pressure at baseline and left ventricular mass
      index, a low flow-mediated vasodilatation conferred an increased risk of
      cardiovascular events (odds ratio 2.67, 95% confidence interval 1.17 to 6.1, P =
      0.02). CONCLUSION: The presence of endothelial dysfunction, as evaluated by flow
      mediated vasodilatation of the brachial artery, identifies hypertensive patients
      at increased risk of nonfatal and fatal cardiovascular events.

PMID- 18622241
TI  - Gender-specific brachial artery blood pressure-independent relationship between
      pulse wave velocity and left ventricular mass index in a group of African
      ancestry.
AB  - AIM: As it is uncertain whether arterial stiffness is related to left ventricular
      mass and left ventricle mean wall thickness independent of blood pressure
      measured at the brachial artery, we aimed to ascertain this effect in never
      treated participants with a high prevalence of risk factors for large artery
      dysfunction. METHODS: The conventional and ambulatory blood pressure-independent
      relations between indices of large artery function and either left ventricular
      mass or mean wall thickness were determined in 309 never-treated randomly
      recruited South Africans of African ancestry with prevalent risk factors for
      large artery changes [24% were hypertensive, 63% were overweight/obese, and 17%
      had diabetes mellitus or abnormal blood glucose control (glycosylated hemoglobin
      A1c > 6.1%)]. Large artery function was assessed from applanation tonometry
      performed at the carotid, radial and femoral arteries and central augmentation
      index and aortic pulse wave velocity (carotid femoral pulse wave velocity)
      derived from these measures. Left ventricular mass indexed for height (left
      ventricular mass index) and mean wall thickness were determined using
      echocardiography. RESULTS: Pulse wave velocity was associated with left
      ventricular mass index (r = 0.67, P < 0.0001) and mean wall thickness (r = 0.61,
      P < 0.0001) in women, but not in men (r = 0.04-0.08) (P < 0.0001 for the
      interaction between pulse wave velocity and gender). On multivariate analysis
      with appropriate adjustments including either conventional systolic blood
      pressure, pulse pressure or mean arterial pressure, pulse wave velocity was
      independently associated with left ventricular mass index (partial r = 0.25, P <
      0.005 after adjustments for systolic blood pressure) and with mean wall thickness
      (partial r = 0.17, P < 0.05 after adjustments for systolic blood pressure) in
      women, but not in men. With the inclusion of 24-h ambulatory rather than
      conventional systolic blood pressure, pulse pressure or mean arterial pressure in
      the regression equation, pulse wave velocity was similarly independently
      associated with left ventricular mass index (partial r = 0.39, P < 0.001 after
      adjustments for 24-h systolic blood pressure) and mean wall thickness (partial r
      = 0.33, P < 0.003 after adjustments for 24-h systolic blood pressure) in women,
      but not in men. Central augmentation index was not independently associated with
      left ventricular mass index or mean wall thickness. In women, the contribution of
      pulse wave velocity to left ventricular mass index or mean wall thickness
      independent of systolic blood pressure (standardized beta-coefficient for left
      ventricular mass index=0.37 +/- 0.13, P < 0.005) was equivalent to the
      contribution of systolic blood pressure (standardized beta-coefficient for left
      ventricular mass index = 0.38 +/- 0.13, P < 0.005). Moreover, after adjusting for
      clinic or ambulatory systolic blood pressure and other confounders, in women
      every one standard deviation increase in pulse wave velocity (2.1 m/s) translated
      into a 4.3 or 6.2 g/m increase in left ventricular mass index, respectively.
      CONCLUSION: Arterial stiffness is associated with left ventricular mass index and
      left ventricle wall thickness independent of conventional or ambulatory blood
      pressure and additional confounders in a never-treated population sample of
      women, but not men, of African ancestry with prevalent risk factors for large
      artery dysfunction.

PMID- 18622242
TI  - Autoantibody against AT1 receptor from preeclamptic patients induces
      vasoconstriction through angiotensin receptor activation.
AB  - Preeclampsia is a serious pathologic complication during pregnancy, and its
      pathogenesis remains poorly understood. Recent studies have demonstrated that
      autoantibodies against angiotensin II type 1A receptor (AT1-AA) are present in
      women with preeclampsia. However, their role in the development of hypertension
      in preeclamptic patients has never been previously investigated. The present
      study was designed to determine whether AT1-AA isolated from the sera of
      preeclamptic patients causes vascular constriction and, if so, to further
      investigate the cellular receptors that mediate their vasoactivity. Blood samples
      were collected from 49 pregnant women (preeclampsia = 31, control = 18) and AT1
      AA was detected using enzyme-linked immunosorbent assay. Vasoconstrictive effect
      of purified IgG from the sera of either preeclamptic patients or normal pregnant
      women was determined in isolated rat thoracic aorta, arteriae cerebri media and
      coronary artery. Compared with normal pregnant women, frequency of AT1-AA
      positive samples was markedly increased in preeclamptic patients (80.7 vs. 5.6%,
      P < 0.01). In isolated thoracic aortic rings, middle cerebral artery and coronary
      artery segments, AT1-AA induced vasoconstriction in a concentration-dependent
      fashion (P < 0.01). The vasoconstrictive effect of AT1-AA was completely blocked
      by losartan, an AT1-receptor antagonist. These data demonstrate that the AT1-AA
      causes significant vascular constriction in large conduit vessel as well as small
      resistant vessels though activation of the AT1 receptor. These results suggest
      that overproduction of AT1-AA is a novel risk factor in pregnant women and may
      play a causative role in the development of hypertension and vascular injury in
      preeclamptic patients.

PMID- 18622243
TI  - Ambulatory blood pressure as an independent determinant of brain atrophy and
      cognitive function in elderly hypertension.
AB  - OBJECTIVE: Recent studies have demonstrated a relationship between brain atrophy
      and hypertension. Systolic hypertension in the elderly has been found to be a
      risk factor for cognitive impairment. We studied the relationship of ambulatory
      blood pressure with brain atrophy and cognitive function. METHODS: We performed
      ambulatory blood pressure monitoring and brain magnetic resonance imaging in 55
      unmedicated elderly hypertensive patients (72.7 +/- 6.0 years old). The volume of
      total brain matter was measured using an intensity contour-mapping algorithm.
      Cognitive function was assessed by mini-mental state examination score. RESULTS:
      Total brain matter volume and cognitive function were significantly correlated (r
      = 0.314, P = 0.02). Total brain matter volume was significantly negatively
      correlated with age (r = -0.365, P = 0.006), 24-h systolic blood pressure (r = 
      0.343, P = 0.01), awake systolic blood pressure (r = -0.278, P = 0.04) and sleep
      systolic blood pressure (r = -0.491, P = 0.0001), and significantly positively
      correlated with male sex (r = 0.493, P = 0.0001), body mass index (r = 0.282, P =
      0.04) and nocturnal systolic blood pressure dipping (r = 0.323, P = 0.02). Mini
      mental state examination score was significantly negatively correlated with age
      (r = -0.277, P = 0.04) and sleep systolic blood pressure (r = -0.360, P = 0.007),
      and significantly positively correlated with nocturnal systolic blood pressure
      dipping (r = 0.402, P = 0.002). In multiple linear regression analysis adjusted
      for age, sex, and body mass index, sleep systolic blood pressure (P = 0.009) was
      more significantly negatively associated with total brain matter volume than was
      either 24-h (P = 0.035) or awake (P = 0.020) systolic blood pressure.
      CONCLUSIONS: In elderly hypertensive patients, absolute ambulatory systolic blood
      pressure level (particularly during sleep) and nocturnal dipping in systolic
      blood pressure were strong indicators of brain matter volume and cognitive
      function.

PMID- 18622244
TI  - Effects of hypertension therapy based on eprosartan on systolic arterial blood
      pressure and cognitive function: primary results of the Observational Study on
      Cognitive function And Systolic Blood Pressure Reduction open-label study.
AB  - BACKGROUND: Recent studies have indicated a relationship between hypertension and
      cognitive function but therapeutic trials of antihypertensive therapy on the
      prevention of cognitive disorders have produced controversial findings. METHODS:
      The Observational Study on Cognitive function And Systolic Blood Pressure
      Reduction is an open-label trial in 28 countries designed to evaluate the impact
      of eprosartan-based therapy on cognitive function. The Mini-Mental State
      Examination was used as a global tool for the comprehensive assessment of
      cognitive function, with an intention to treat a cohort of 25 745 hypertensive
      patients aged at least 50 years during a follow-up interval of 6 months. Blood
      pressure therapy was initiated with eprosartan 600 mg/day with provision for
      additional medication to be introduced after 1 month in patients with
      insufficient blood pressure response. RESULTS: Use of eprosartan, either as
      monotherapy or in combination regimens, was associated with a substantial
      reduction in arterial blood pressure from 161.9/93.1 mmHg at baseline to
      136.1/80.8 mmHg at 6 months (P < 0.0001). The overall mean Mini-Mental State
      Examination score at completion of follow-up was 27.9 +/- 2.9 compared with 27.1
      +/- 3.4 at baseline (P < 0.0001). A significant correlation was shown between the
      mean absolute response of Mini-Mental State Examination and the magnitude of
      systolic blood pressure reduction. At the end of the study, patients with
      systolic blood pressure less than 140 mmHg had a larger improvement in Mini
      Mental State Examination [0.88 +/- 0.01 (SEM)] than those with systolic blood
      pressure between 140 and 159 mmHg [0.69 +/- 0.02 (SEM); P < 0.001], or than those
      with systolic blood pressure of at least 160 mmHg [0.38 +/- 0.05 (SEM); P <
      0.0001]. Furthermore, cognitive decline was demonstrated in multiple linear
      regression to be independently associated with age [odds ratio 1.19 (1.14;
      1.25)], Mini-Mental State Examination at baseline [odds ratio 1.19 (1.14; 1.25)],
      systolic blood pressure at baseline [odds ratio 1.20 (1.13; 1.27)] and systolic
      blood pressure reduction [odds ratio 0.77 (0.73; 0.82)]. CONCLUSION: The results
      of the Observational Study on Cognitive function And Systolic Blood Pressure
      Reduction are supportive of the proposition that antihypertensive therapy based
      on drugs that target the renin-angiotensin system is associated with preservation
      of cognitive function.

PMID- 18622245
TI  - Simvastatin abates development of renal fibrosis in experimental renovascular
      disease.
AB  - BACKGROUND AND OBJECTIVES: Epithelial-to-mesenchymal transition contributes to
      renal fibrogenesis, which is regulated by profibrogenic and antifibrogenic
      mediators. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors can prevent
      epithelial-to-mesenchymal transition in some models. Therefore, we tested the
      hypothesis that epithelial-to-mesenchymal transition participates in renal injury
      in porcine atherosclerotic renovascular disease and can be attenuated by
      simvastatin. METHODS: Renal hemodynamics, function, and endothelial function were
      quantified in vivo in pigs after 12 weeks of combined hypercholesterolemia +
      renal artery stenosis without (n = 8) or with oral simvastatin supplementation
      (1.2 mg/kg, n = 6), and in controls (n = 8). Ex-vivo studies assessed renal
      immunoreactivity to fibrogenic factors and renal histology. RESULTS: Blood
      pressure, cholesterol levels, and basal renal function were similar in treated
      and untreated pigs with hypercholesterolemia + renal artery stenosis.
      Hypercholesterolemia + renal artery stenosis significantly upregulated renal
      transforming growth factor-beta signaling and elicited epithelial-to-mesenchymal
      transition, accompanied by glomerulosclerosis and renal fibrosis. Simvastatin did
      not affect smad 2/3 expression but upregulated expression of hepatocyte growth
      factor, bone morphogenetic factor-7, and smad 7 and prevented most of these renal
      structural and functional alterations. Furthermore, simvastatin improved renal
      blood flow response to endothelium-dependent challenge (+111.3 +/- 35.5 vs. -30.4
      +/- 18.7 ml/min in untreated pigs, P < 0.05). CONCLUSION: Simvastatin upregulates
      inhibitors of transforming growth factor-beta signaling, attenuates epithelial-to
      mesenchymal transition, and decreases renal fibrosis in hypercholesterolemia +
      renal artery stenosis. These lipid-lowering-independent effects result in
      improvement of renal function, suggesting clinically valuable potential for
      statins in preserving the stenotic kidney and limiting deterioration of renal
      function in atherosclerotic renovascular disease.

PMID- 18622246
TI  - Oxonic acid-induced hyperuricemia elevates plasma aldosterone in experimental
      renal insufficiency.
AB  - BACKGROUND: Hyperuricemia is associated with renal insufficiency and may
      predispose to Na retention and hypertension. Whether hyperuricemia plays a causal
      role in the pathogenesis of cardiovascular disease remains controversial.
      OBJECTIVE: We examined the effects of hyperuricemia on circulating and renal
      components of the renin-angiotensin-aldosterone system in experimental renal
      insufficiency. METHODS: Three weeks after 5/6 nephrectomy or sham-operation, rats
      were put on 2.0% oxonic acid diet for 9 weeks. Blood pressure was monitored using
      tail-cuff, and blood, urine, and kidney samples were taken, as appropriate.
      Kidney angiotensin-converting enzyme, angiotensin-converting enzyme 2 and
      angiotensin II receptors (AT1R, AT2R) were examined using real-time reverse
      transcriptase-PCR and autoradiography. RESULTS: Oxonic acid diet increased plasma
      uric acid by 80-90 micromol/l, while blood pressure was elevated only in
      hyperuricemic 5/6 nephrectomy rats (18 mmHg). Creatinine clearance was reduced by
      60% in both 5/6 nephrectomy groups and by 25% in hyperuricemic Sham rats. The 5/6
      nephrectomy group showed over 90% suppression of plasma renin activity, whereas
      the Sham + oxonic acid diet group showed 1.2 and 1.4-fold, and 5/6 nephrectomy +
      oxonic acid diet group 2.5 and 2.3-fold increases in plasma renin activity and
      plasma aldosterone, respectively. Hyperuricemia increased K and decreased Na
      excretion in Sham and 5/6 nephrectomy rats, leading to a more than 1.6-fold
      increase in urine K to Na ratio. No changes in kidney angiotensin-converting
      enzyme, angiotensin-converting enzyme 2, AT1R or AT2R were detected that could
      explain the hyperuricemia-induced alteration in Na-K balance. CONCLUSION: As
      oxonic acid diet increased plasma renin activity, plasma aldosterone, and urine K
      to Na ratio, these changes may play a significant role in the harmful
      cardiovascular actions of hyperuricemia.

PMID- 18622248
TI  - Effects of papillary muscles and trabeculae on left ventricular quantification:
      increased impact of methodological variability in patients with left ventricular
      hypertrophy.
AB  - BACKGROUND: Accurate quantification of left ventricular mass and ejection
      fraction is important for patients with left ventricular hypertrophy. Although
      cardiac magnetic resonance imaging has been proposed as a standard for these
      indices, prior studies have variably included papillary muscles and trabeculae in
      myocardial volume. This study investigated the contribution of papillary muscles
      and trabeculae to left ventricular quantification in relation to the presence and
      pattern of hypertrophy. METHODS: Cardiac magnetic resonance quantification was
      performed on patients with concentric or eccentric hypertrophy and normal
      controls (20 per group) using two established methods that included papillary
      muscles and trabeculae in myocardium (method 1) or intracavitary (method 2)
      volumes. RESULTS: Among all patients, papillary muscles and trabeculae accounted
      for 10.5% of ventricular mass, with greater contribution with left ventricular
      hypertrophy than normals (12.6 vs. 6.2%, P < 0.001). Papillary muscles and
      trabeculae mass correlated with ventricular wall mass (r = 0.53) and end
      diastolic volume (r = 0.52; P < 0.001). Papillary muscles and trabeculae
      inclusion in myocardium (method 1) yielded smaller differences with a standard of
      mass quantification from linear ventricular measurements than did method 2 (P <
      0.001). Method 1 in comparison with method 2 yielded differences in left
      ventricular mass, ejection fraction and volume in all groups, especially in
      patients with hypertrophy: the difference in ventricular mass index was three
      fold to six-fold greater in hypertrophy than normal groups (P < 0.001).
      Difference in ejection fraction, greatest in concentric hypertrophy (P < 0.001),
      was independently related to papillary muscles and trabeculae mass, ventricular
      wall mass, and smaller ventricular volume (R = 0.56, P < 0.001). CONCLUSION:
      Established cardiac magnetic resonance methods yield differences in left
      ventricular quantification due to variable exclusion of papillary muscles and
      trabeculae from myocardium. The relative impact of papillary muscles and
      trabeculae exclusion on calculated mass and ejection fraction is increased among
      patients with hypertrophy-associated left ventricular remodeling.

PMID- 18622247
TI  - Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive
      hypertension: role of activation of AMP-activated protein kinase and inhibition
      of Akt.
AB  - OBJECTIVE: Cardiac hypertrophy is common in diabetes and an independent risk
      factor for cardiac morbidity and mortality. We investigated the effects of
      pioglitazone on cardiac hypertrophy and hypertrophic signaling in Dahl salt
      sensitive hypertensive rats. METHODS: Dahl salt-sensitive rats were fed a high
      salt diet from 7 weeks of age and treated with pioglitazone (2.5 mg/kg per day)
      or vehicle from 7 to 11 weeks. RESULTS: The vehicle-treated rats developed left
      ventricular hypertrophy and fibrosis as well as left ventricular diastolic
      dysfunction. The serum level of adiponectin and the phosphorylation of AMP
      activated protein kinase in the myocardium did not differ between the vehicle
      treated rats and control rats maintained on a normal diet. The phosphorylation of
      Akt, mammalian target of rapamycin, and p70S6 kinase as well as the total protein
      content were increased in the heart of vehicle-treated rats compared with control
      rats, and these changes were blocked by treatment with pioglitazone. Pioglitazone
      treatment also ameliorated left ventricular hypertrophy and fibrosis, improved
      diastolic function, and increased both the serum adiponectin concentration and
      the level of AMP-activated protein kinase phosphorylation in the heart.
      CONCLUSIONS: Long-term administration of pioglitazone attenuated left ventricular
      hypertrophy and fibrosis as well as inhibited phosphorylation of mammalian target
      of rapamycin and p70S6 kinase in the heart of hypertensive rats. The beneficial
      cardiac effects of pioglitazone are likely attributable, at least partly, both to
      the activation of AMP-activated protein kinase signaling through stimulation of
      adiponectin secretion and to the inhibition of Akt signaling.

PMID- 18622249
TI  - Myocardial perfusion in hypertensive patients with normal coronary angiograms.
AB  - BACKGROUND: Pressure-induced left ventricular hypertrophy is one of the
      mechanisms responsible for an impaired coronary vasodilating capacity leading to
      myocardial ischemia and angina. The aim of the study was to investigate
      myocardial perfusion using cardiovascular magnetic resonance in patients with
      arterial hypertension and a history of chest pain and normal coronary
      angiography, and to estimate the influence of left ventricular hypertrophy on the
      parameters of myocardial perfusion. METHODS: The study included 102 patients
      (mean age 55.4 +/- 7.7 years) with well controlled hypertension and 12 healthy
      volunteers. In 96 patients, myocardial first-pass perfusion cardiovascular
      magnetic resonance both at rest and during an infusion of adenosine 140
      microg/kg/min was performed. Semiquantitative perfusion analysis was performed by
      using the upslope of myocardial signal enhancement to derive the myocardial
      perfusion index and the myocardial perfusion reserve index. The study group was
      divided according to the presence of left ventricular hypertrophy in the
      cardiovascular magnetic resonance examination: group with left ventricular
      hypertrophy (n = 40) and without left ventricular hypertrophy (n = 56). RESULTS:
      Independent of the presence of left ventricular hypertrophy, there were
      significant differences in baseline myocardial perfusion index between
      hypertensive patients and controls (0.13 +/- 0.07 vs. 0.04 +/- 0.01; P < 0.001),
      and in stress myocardial perfusion index (hypertensive patients 0.21 +/- 0.10 vs.
      controls 0.09 +/- 0.03; P < 0.001). In hypertensive patients, the myocardial
      perfusion reserve index was reduced in the mid and apical portions of the left
      ventricle (1.71 +/- 1.1 vs. 2.52 +/- 0.83; P < 0.02). There was no significant
      correlation of myocardial perfusion reserve index with left ventricular mass or
      hypertrophy. CONCLUSION: In patients with mild or moderate hypertension and a
      history of chest pain with normal coronary angiography, there is regional
      myocardial perfusion reserve impairment that is independent of the presence of
      left ventricular hypertrophy and may be a reason for angina.

PMID- 18622250
TI  - Effect on blood pressure of lumiracoxib versus ibuprofen in patients with
      osteoarthritis and controlled hypertension: a randomized trial.
AB  - OBJECTIVES: Nonsteroidal anti-inflammatory drugs vary in their impact on blood
      pressure and the effect of lumiracoxib 100 mg once daily has not been studied
      previously. To examine whether lumiracoxib 100 mg once daily would result in
      lower 24-h mean systolic ambulatory blood pressure than ibuprofen 600 mg three
      times daily in osteoarthritis patients with controlled hypertension, a 4-week,
      randomized, double-blind, parallel-group study was conducted in 79 centres in
      nine countries. METHODS: Hypertensive osteoarthritis patients of 50 years at
      least whose office blood pressure was less than 140/90 mmHg on stable
      antihypertensive treatment were randomized to lumiracoxib (n = 394) 100 mg once
      daily or ibuprofen 600 mg three times daily (n = 393) and 24-h ambulatory blood
      pressure monitoring was performed at baseline and end of study. The primary
      outcome measure was a comparison of the change in 24-h mean systolic ambulatory
      blood pressure from baseline to week 4. Secondary analyses included other blood
      pressure-related endpoints and efficacy (pain) measurements. RESULTS: Compared
      with baseline, the 24-h mean systolic ambulatory blood pressure (least square
      mean) decreased in lumiracoxib-treated patients (-2.7 mmHg) and increased in
      ibuprofen-treated patients (+2.2 mmHg) at 4 weeks, estimated difference -5.0 mmHg
      (95% confidence interval -6.1 to -3.8) in favour of lumiracoxib. The 24-h mean
      diastolic ambulatory blood pressure changes were -1.5 mmHg (lumiracoxib), +0.5
      mmHg (ibuprofen), difference -2.0 mmHg (95% confidence interval -2.7 to -1.3).
      Efficacy results were comparable. CONCLUSIONS: Treatment with lumiracoxib 100 mg
      once daily resulted in clinically significant lower blood pressure compared with
      ibuprofen 600 mg three times daily in osteoarthritis patients with well
      controlled hypertension.

PMID- 18622251
TI  - Effect of antihypertensive treatment on retinal microvascular changes in
      hypertension.
AB  - OBJECTIVE: Hypertension causes arteriolar narrowing and rarefaction in the
      retinal circulation, but the extent to which these changes are reversible by
      antihypertensive treatment is not well studied. We compared the effect of
      antihypertensive treatment with a calcium-channel-blocker-based regimen and an
      angiotensin-converting-enzyme-inhibitor-based regimen on the retinal
      microvasculature. METHODS: Twenty-five patients (17 men, age range 24-71 years)
      with untreated hypertension were randomized to treatment with an amlodipine-based
      (n = 12) or lisinopril-based (n = 13) regimen in a double-blind, prospective
      parallel limb trial for 52 weeks. Measurements of blood pressure and the retinal
      microvasculature were made at baseline and at the end of the study. RESULTS: Both
      the amlodipine-based and lisinopril-based treatments reduced blood pressure to
      similar extents. Blood pressure reduction was associated with a reduction in
      arteriolar narrowing, a widening of arteriolar branch angle and an increase in
      arteriolar density. There were no significant differences between the two
      treatment regimens. CONCLUSION: Antihypertensive treatment is associated with
      improvement in arteriolar narrowing and rarefaction. Improved microvascular
      structure may contribute to the beneficial effects of antihypertensive treatment
      in hypertension.

PMID- 18622252
TI  - Primary aldosteronism: an update on screening, diagnosis and treatment.

PMID- 18622254
TI  - Pulmonary venous flow in hypertension: ready for prime time?

PMID- 18622255
TI  - The relationship between CYP4A11 and human hypertension.

PMID- 18622257
TI  - Interactions between the single nucleotide polymorphisms in the homocysteine
      pathway (MTHFR 677C>T, MTHFR 1298 A>C, and CBSins) and the efficacy of HMG-CoA
      reductase inhibitors in preventing cardiovascular disease in high-risk patients
      of hypertension: the GenHAT study.
AB  - BACKGROUND: High homocysteine blood concentrations predispose to coronary artery
      disease and statins influence homocysteine levels. AIM: To study whether genes
      that regulate homocysteine metabolism interact with statins to modify the risk of
      coronary heart disease (CHD) and other cardiovascular outcomes. METHODS: The
      Genetics of Hypertension Associated Treatment is an ancillary study of the
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT). The genotyped population in the Lipid-Lowering Trial of
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      included 9624 participants randomly assigned to pravastatin or to usual care. The
      efficacy of pravastatin in reducing risk of all-cause mortality and CHD was
      compared among genotype strata (MTHFR 677 CC, CT, and TT, MTHFR 1298 AA, AC, and
      CC, CBSins DD and I) by examining an interaction term in a proportional hazards
      model. RESULTS: No evidence existed of a pharmacogenetic effect on statins with
      the MTHFR 1298 A>C genotype for CHD risk. However, in persons with the CC variant
      for the MTHFR 677 C>T genotype, a significantly protective effect against CHD
      [0.71 (95% CI 0.58-0.87)] was shown, although in the CT [1.25 (95% CI 0.97-1.61)]
      and TT groups [0.80 (95% CI 0.50-1.28)] there were no such effects (interaction
      hazard ratio P=0.004). The CBSins, I+ variant was associated with a significantly
      reduced risk for CHD among those on statin treatment [0.58 (95% CI 0.44-0.78)]
      whereas the DD genotype showed no effect of statin therapy [1.01 (95% CI 0.84
      1.20; P=0.002 for interaction]. For the endpoint all-cause mortality, no
      significant differences in efficacy were noted. CONCLUSION: Polymorphisms in
      genes in the homocysteine pathway (MTHFR 677 C>T and CBSins) appear to modify the
      efficacy of pravastatin in reducing risk of cardiovascular events.

PMID- 18622258
TI  - Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones
      among postmenopausal Chinese women.
AB  - OBJECTIVE: Circulating estrogen levels have been related to the risk of several
      female cancers. Blood levels of estrogen are controlled by estrogen synthesis
      enzymes. Genetic variation of estrogen genes thus may influence circulating
      estrogen levels. We investigated the associations of genetic polymorphisms in
      CYP19A1, a critical gene involved in estrogen synthesis, with plasma levels of
      sex hormones among postmenopausal Chinese women. METHODS: Included in this study
      were 345 postmenopausal community controls from a population-based case-control
      study conducted in Shanghai. Fasting blood samples from those women were measured
      for blood estradiol, estrone, estrone sulfate, and testosterone. A total of 19
      genetic polymorphisms in CYP19A1 were genotyped using ABI7900 or PCR-restriction
      fragment length polymorphism methods. Differences in plasma levels of hormones by
      genotype were examined using variance analysis. RESULT: The geometric means of
      plasma levels of estradiol, estrone, estrone sulfate, and testosterone were 10.1,
      16.8, 969.0, and 202.9 pg/ml, respectively, for this study population. We found
      that plasma levels of estrone were associated with rs28566535 (P=0.0180),
      rs730154 (P=0.0141), and rs936306 (P=0.0274) in block 2. In the same block, the
      haplotype CGCTA was related to level of estrone (P=0.0064). Single nucleotide
      polymorphism rs1902584 in block 1 was associated with estradiol only in
      overweight postmenopausal women. No clear association with sex hormones was noted
      for the other genetic polymorphisms evaluated in the study. CONCLUSION: Single
      nucleotide polymorphisms in blocks 1 and 2 of the CYP19A1 gene are related to
      plasma levels of estrogen among postmenopausal Chinese women and may therefore
      play an important role in the etiology of hormone-related cancers.

PMID- 18622259
TI  - Characterization of the biochemical and structural phenotypes of four CYP1B1
      mutations observed in individuals with primary congenital glaucoma.
AB  - OBJECTIVE: The objective of this study was to examine the biochemical and
      physical properties of cytochrome P450 1B1 (CYP1B1) mutants, test our hypothesis
      that primary congenital glaucoma (PCG)-causing mutants have altered metabolic
      activity, and correlate these to structural changes in the molecule. METHODS:
      CYP1B1.1 cDNA was mutated to four forms found in individuals with the PCG
      phenotype, Y81N, E229K, A330F, and R368H. Expression and stability of the mutant
      hemoproteins and their ability to metabolize beta-estradiol, arachidonic acid,
      and retinoids, were determined. Alterations in mutant properties were related to
      structural changes by in silico examination, on the basis of the CYP1A2 crystal
      structure. RESULTS: CYP1B1 mutations strongly affected the stability, ease of
      heterologous expression, and enzymatic properties of the protein. These were
      related to the location of the amino acid substitutions in the CYP1B1 structure.
      Three of the mutations involve residues located on the surface of CYP1B1, Y81N,
      and E229K near the distal surface, and R368H near the proximal surface. The
      former two substitutions, Y81N and E229K, caused greatly reduced stability at 4
      degrees C. Y81N severely inhibited all substrate turnover, but E229K only
      inhibited arachidonate turnover and exhibited minimal effect on efficiency of
      retinoid metabolism and estradiol metabolism. The R368H mutation is relatively
      conservative, affecting charge-pairing with the deeper-located D374, but it
      severely inhibited metabolism of all substrates tested, and, like Y81N,
      expression of the enzyme is less facile than CYP1B1wt. The A330F mutation
      replaces a small alanine by a bulky phenylalanine in the enzyme active site and
      had major impact on substrate binding, turnover, uncoupling, and metabolite
      pattern. CONCLUSION: Consistent with the hypothesis, these PCG-related mutations
      cause identifiable structural changes negatively impacting CYP1B1 biochemistry
      and stability.

PMID- 18622260
TI  - Common genetic variation in six lipid-related and statin-related genes, statin
      use and risk of incident nonfatal myocardial infarction and stroke.
AB  - OBJECTIVE: Genetic polymorphisms are associated with lipid-lowering response to
      statins, but generalizeability to disease endpoints is unclear. The association
      between 82 common single nucleotide polymorphisms (SNPs) in six lipid-related or
      statin-related genes (ABCB1, CETP, HMGCR, LDLR, LIPC, NOS3) and incident nonfatal
      myocardial infarction (MI) and ischemic stroke was analyzed according to current
      statin use and overall in a population-based case-control study (856 MI, 368
      stroke, 2686 controls). METHODS: Common SNPs were chosen from resequencing data
      using pairwise linkage disequilibrium. Gene-level analyses (testing global
      association within a gene) and SNP-level analyses (comparing the number of
      observed vs. expected associations across all genes) were performed using
      logistic regression, setting nominal statistical significance at P value of less
      than 0.05. RESULTS: No gene-level interactions with statin use on MI or stroke
      were identified. Across all genes, two SNP-statin interactions on MI were
      observed (one ABCB1, one LIPC) and five interactions on stroke (one CETP, four
      LIPC). The strongest SNP-statin interaction was for synonymous CETP SNP rs5883 on
      stroke (P=0.008). Gene-level associations were present for LIPC and MI (P=0.026),
      but not other genes or outcomes. SNP-level associations included three SNPs with
      MI (one LDLR, two LIPC) and two SNPs with stroke (one CETP, one LDLR). The number
      of observed SNP associations was no greater than expected by chance. CONCLUSION:
      Several potential novel associations or interactions of SNPs in ABCB1, CETP,
      LDLR, and LIPC with MI and stroke were identified; however, our results should be
      regarded as hypothesis generating until corroborated by other studies.

PMID- 18622261
TI  - Single nucleotide polymorphism discovery and functional assessment of variation
      in the UDP-glucuronosyltransferase 2B7 gene.
AB  - OBJECTIVE: UDP-glucuronosyltransferase 2B7 (UGT2B7) plays a central role in the
      liver-mediated biotransformation of endogenous and exogenous compounds. The
      genetic basis of interindividual variability in UGT2B7 function is unknown. This
      study aimed to discover novel gene variants of functional significance. METHODS:
      Caucasian human livers (n=54) were used. UGT2B7 was resequenced in 12 samples
      [(six highest and six lowest for the formation of morphine-3-glucuronide (M3G)].
      Haplotype-tagging single nucleotide polymorphisms were genotyped in the entire
      sample set. Samples were phenotyped for mRNA expression. RESULTS: 10 haplotype
      tagging single nucleotide polymorphisms were identified and their haplotypes were
      inferred. Haplotype 4 (-45597G; -6682_-6683A; 372A; IVS1+9_IVS1+10A; IVS1+829T;
      IVS1+985G; IVS1+999C; IVS1+1250G; 801T; IVS4+185C) (frequency of 0.12) was
      associated with an increase in enzyme activity and gene expression. The 1/4 and
      4/6 diplotypes had higher M3G formation compared with 1/1 (P<0.05) and 2/3
      (P<0.01) diplotypes. Diplotypes containing haplotype 4 resulted in a significant
      45% average increase in the formation of M3G compared with diplotypes without
      haplotype 4 (P=0.002). There was also an association between haplotype 4 and
      increased mRNA expression. IVS1+985A>G, 735A>G, and 1062C>T are the putative
      functional variants of haplotype 4. We also identified two mRNA splicing variants
      (UGT2B7_v2 and UGT2B7_v3) splicing out exon 1, 4, 5, and 6 but sharing exons 2
      and 3 with the involvement of additional 5' exons. UGT2B7_v2 was detected in all
      livers tested, but UGT2B7_v3 was present at much lower levels compared with
      UGT2B7_v2. The UGT2B7 reference sequence mRNA is now named UGT2B7_v1. CONCLUSION:
      UGT2B7 haplotype 4 is functional and its effects on the biotransformation of
      UGT2B7 substrates should be tested in controlled clinical trials. Biochemical
      studies should investigate the functional role of the newly discovered mRNA
      splicing variants.

PMID- 18622262
TI  - Impact of the endothelial nitric oxide synthase gene G894T polymorphism on renal
      endothelial function in patients with type 2 diabetes.
AB  - OBJECTIVE: Endothelial dysfunction and increased oxidative stress contribute to
      the progression of diabetic nephropathy. To analyze the functional significance
      of the G894T polymorphism of NOS3, the gene encoding endothelial nitric oxide
      synthase (NOS), we assessed basal nitric oxide activity and the amount of
      oxidative stress in the renal circulation of patients with type 2 diabetes.
      METHODS: Renal plasma flow (RPF) was assessed by steady-state input clearance
      technique with sodium para-aminohippurate in 84 patients with type 2 diabetes and
      84 patients without diabetes. RPF was measured at baseline and after the infusion
      of the NOS inhibitor N-monomethyl-L-arginine (4.25 mg/kg); the substrate of NOS L
      arginine (100 mg/kg); and coinfusion of vitamin C (3 g) with L-arginine (100
      mg/kg). RESULTS: The decrease of RPF to N-monomethyl-L-arginine was similar
      between carriers of the T allele and homozygous carriers of the G allele in
      patients with diabetes (-56+/-40 vs. -68.1+/-74 ml/min/1.73 m, P=0.342) and
      patients without diabetes (-66.7+/-81 vs. -58.3+/-63 ml/min/1.73 m, P=0.606). In
      patients with diabetes, however, carriers of the T allele revealed a more
      pronounced increase of RPF to coinfusion of vitamin C with L-arginine than
      homozygous carriers of the G allele (61.8+/-75 vs. 22.3+/-73 ml/min/1.73 m,
      P=0.021), whereas in patients without diabetes the response of RPF to coinfusion
      of vitamin C with L-arginine was similar between both groups (46.2+/-80 vs.
      70.7+/-86 ml/min/1.73 m, P=0.217). Gene-environment interaction between disease
      (diabetes) and genotype (genotype GG vs. genotype GT/TT) was observed for
      increase of RPF to coinfusion of vitamin C with L-arginine (P=0.020). CONCLUSION:
      G894T polymorphism of NOS3 has no impact on the basal nitric oxide activity of
      renal circulation. In contrast, the T allele is associated with increased
      oxidative stress in the renal circulation in patients with diabetes suggesting a
      specific role of the G894T polymorphism in the pathogenesis of diabetic
      nephropathy.

PMID- 18622263
TI  - Genetic polymorphisms in the 5'-flanking region of human UDP
      glucuronosyltransferase 2B7 affect the Nrf2-dependent transcriptional regulation.
AB  - OBJECTIVES: Human uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) plays
      important roles in the metabolism of some clinical drugs, carcinogens, and
      steroid hormones. The molecular mechanisms of the inducible expression of UGT2B7
      in response to xenobiotics have not been fully clarified. We sought to
      investigate whether the UGT2B7 is under the control of NF-E2 p45-related factor 2
      (Nrf2), a key transcriptional factor regulating the expression of cytoprotective
      enzymes. METHODS: HepG2, HuH7, HLE, and Caco-2 cells were treated with
      sulforaphane (SFN), and the UGT2B7 mRNA levels were determined by real-time
      reverse transcriptase PCR. These cells were genotyped for the UGT2B7*2 (H268Y)
      allele using the PCR-restriction fragment length polymorphism method. Luciferase
      analyses and gel shift analyses were performed to identify the responsive regions
      for Nrf2 signaling. RESULTS: The UGT2B7 mRNA was induced by SFN in HepG2 and HuH7
      genotyped as UGT2B7*1/*1, but not in HLE and Caco-2 cells genotyped as
      UGT2B7*2/*2. In HepG2 cells, the UGT2B7 protein level and morphine
      glucuronosyltransferase activity were also significantly induced by SFN. The
      induction was prominently decreased with small interfering RNA for Nrf2. In the
      5'-flanking region (-2.5 kb) of the UGT2B7*2 allele, a 324-base pair insertion at
      -2067 and 12 single nucleotide polymorphisms simultaneously existed. Luciferase
      analyses and gel shift analyses revealed that an antioxidant responsive element
      at -1170 was responsible for the transactivation by Nrf2. In addition, a region
      from -990 to -858 on the UGT2B7*1 allele was also responsible for the
      transactivation by Nrf2. Abrogation of the Nrf2-dependent transactivation of the
      UGT2B7*2 allele was owing to the single nucleotide polymorphism -900A>G.
      CONCLUSION: UGT2B7 is transcriptionally regulated by Nrf2, but the mechanism is
      hindered by polymorphisms in the promoter region of UGT2B7*2. The allele-specific
      mechanism may cause variability of the glucuronidation in response to oxidative
      stress.

PMID- 18622264
TI  - Association between a polymorphism of the HTR3A gene and therapeutic response to
      risperidone treatment in drug-naive Chinese schizophrenia patients.
AB  - OBJECTIVES: Certain components of the serotonin system have been known for some
      time to be risk factors for schizophrenia. Few studies have, however, focused on
      the association between the therapeutic responses to atypical antipsychotics,
      such as risperidone, and polymorphisms of the 5-HT3 receptor, the only ionotropic
      ligand-gated serotonin receptor, even though there have been some genetic clues
      linking HTR3A and schizophrenia. We therefore postulated that such a polymorphism
      might be an explanatory factor in the diversity of response to risperidone
      treatment. METHODS: The study recruited 107 drug-naive Chinese schizophrenia
      patients who were given 8 weeks of risperidone monotherapy and it explored three
      of four single nucleotide polymorphisms spanning HTR3A for possible association
      with therapeutic improvement, using the Positive and Negative Symptom Scale.
      RESULTS: Significant correlation between the baseline score and therapeutic
      improvement was observed in each subscale (P<0.001). Statistical analysis
      revealed association between genotypes of g.14396A>G polymorphism (rs1176713) and
      score reductions of negative and general subscales after adjusting for the
      influence of the baseline scores of each subscale [P (F, d.f.)=0.026 (3.763, 2),
      0.023 (3.937, 2) respectively]. One haplotype, C-A-G, contributed to an effective
      response in general symptoms (chi(2)=7.3, P=0.007, odds ratio=3.371). CONCLUSION:
      The results of this study are the first to suggest that the polymorphism of HTR3A
      may be a useful predictor of therapeutic response to risperidone treatment in
      Chinese schizophrenic patients, although these conclusions should be treated with
      caution because of the intricacy of the variety of the therapeutic effects to
      risperidone.

PMID- 18622265
TI  - A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted
      desensitization of beta2-adrenergic receptors.
AB  - Beta-agonist treatment of asthma displays substantial interindividual variation,
      which has prompted polymorphism discovery and characterization of beta2
      adrenergic (beta2AR) signaling genes. beta2AR function undergoes desensitization
      during persistent agonist exposure because of receptor phosphorylation by G
      protein coupled receptor kinases (GRKs). GRK5 was found to be highly expressed in
      airway smooth muscle, the tissue target for beta-agonists. The coding region is
      polymorphic at codon 41, where Gln can be substituted by Leu (minor allele), but
      almost exclusively in those of African descent. In transfected cells, GRK5-Leu41
      evoked a greater degree of agonist-promoted desensitization of adenylyl cyclase
      compared with GRK5-Gln41. Consistent with this functional effect, agonist
      promoted beta2AR phosphorylation was greater in cells expressing GRK5-Leu41, as
      was the rate of agonist-promoted receptor internalization. In studies with
      mutated beta2AR lacking PKA-phosphorylation sites, this phenotype was confirmed
      as being GRK-specific. So, GRK5-Leu41 represents a gain-of-function polymorphism
      that evokes enhanced loss-of-function of beta2AR during persistent agonist
      exposure, and thus may contribute to beta-agonist variability in asthma treatment
      of African-Americans.

PMID- 18622266
TI  - Chromosome 17: association of a large inversion polymorphism with corticosteroid
      response in asthma.
AB  - A 900-kb inversion exists within a large region of conserved linkage
      disequilibrium (LD) on chromosome 17. CRHR1 is located within the inversion
      region and associated with inhaled corticosteroid response in asthma. We
      hypothesized that CRHR1 variants are in LD with the inversion, supporting a
      potential role for natural selection in the genetic response to corticosteroids.
      We genotyped six single nucleotide polymorphisms (SNPs) spanning chromosome 17:
      40,410,565-42,372,240, including four SNPs defining inversion status. Similar
      allele frequencies and strong LD were noted between the inversion and a CRHR1 SNP
      previously associated with lung function response to inhaled corticosteroids.
      Each inversion-defining SNP was strongly associated with inhaled corticosteroid
      response in adult asthma (P values 0.002-0.005). The CRHR1 response to inhaled
      corticosteroids may thus be explained by natural selection resulting from
      inversion status or by long-range LD with another gene. Additional
      pharmacogenetic investigations into regions of chromosomal diversity, including
      copy number variation and inversions, are warranted.

PMID- 18622267
TI  - Modest reactivation of the mutant FMR1 gene by valproic acid is accompanied by
      histone modifications but not DNA demethylation.
AB  - Fragile X syndrome (FXS), the leading cause of inherited mental retardation, is
      due to expansion and methylation of a CGG sequence in the FMR1 gene, which result
      in its silencing. We previously demonstrated a reactivation of FMR1 in FXS cells
      treated with the DNA demethylating drug 5-azadeoxycytidine, and, to a lesser
      extent, with the histone deacetylating drug butyrate. To identify other
      reactivating drugs, we now treated three FXS lymphoblastoid cell lines with
      valproic acid (VPA), a well-known antiepileptic drug, causing histone deacetylase
      inhibition and, possibly, DNA demethylation. After VPA treatment, FMR1-mRNA
      levels were low and FMRP protein was undetectable. The gene remained methylated,
      whereas histones were acetylated and a modest variation of histone methylation
      was observed. These results confirm the histone hyperacetylating effect of VPA
      but do not support its putative DNA demethylation activity. The primary role of
      DNA demethylation in the reactivation of the FMR1 gene was confirmed.

PMID- 18622269
TI  - Promises and obstacles for the blockade of CD40-CD40L interactions in
      allotransplantation.
AB  - Although clinical trials using anti-CD40L mAb have been halted, blockade of CD40
      CD40L interactions has given promising results in rodent and nonhuman primate
      models. Recently, new insights into the consequences of blocking CD40-CD40L
      interactions have led to the possibility of overcoming the thromboembolic
      complications previously associated with this strategy and may pave the way for
      successful tolerance induction. This mini review will address the issues relating
      to CD40-CD40L blockade in allotransplantation.

PMID- 18622268
TI  - The multiple facets of toll-like receptors in transplantation biology.
AB  - Toll-like receptors (TLRs) belong to a family of pattern-recognition receptors
      for microbial products and endogenous molecules released by stressed cells.
      Experimental studies show that TLRs are involved in the process of acute
      allograft rejection and that their activation can prevent transplantation
      tolerance. Herein, we review the expression of TLRs and the impact of TLR
      signaling in different cell types in grafted organs including antigen-presenting
      cells, T and B lymphocytes, epithelial and endothelial cells. We then discuss the
      involvement of TLRs in the different phases of the rejection phenomenon and the
      impact of TLR-mediated events on regulatory circuits which dampen alloimmune
      responses.

PMID- 18622270
TI  - Evidence in transplantation: randomized versus nonrandomized studies.

PMID- 18622271
TI  - Expanding the evidence base in transplantation: the complementary roles of
      randomized controlled trials and outcomes research.
AB  - Transplantation offers a unique opportunity to demonstrate the complementary
      roles of randomized controlled trials and outcome research. The surgery and
      collaboration necessary for the transplant procedure makes randomization and
      blinding difficult. Because essentially every recipient is included in a
      transplant registry, sampling bias is minimized. Regulatory agencies generally do
      not consider outcomes research when assessing efficacy of new drugs or medical
      interventions. This workgroup summary examines the suitability of outcomes
      research to complement results of randomized controlled trials and related
      issues: efficacy versus effectiveness, internal versus external validity, data
      types, limitations, and analysis methodologies. Many advances in outcomes
      research have been pioneered in transplantation. A case is made for regulatory
      and reimbursement authorities to use outcomes research when making efficacy,
      effectiveness, and coverage decisions in transplantation.

PMID- 18622272
TI  - Randomization is essential for progress in transplant medicine.
AB  - Improvements in immunosuppressive regimens are likely to be moderate in size.
      Therefore, studies to detect them reliably require a guarantee of small biases
      (so randomization is essential) and small random errors. Even after adjustment,
      nonrandomized studies may have large biases, so are not a suitable alternative to
      large randomized trials.

PMID- 18622273
TI  - Complementarity comes of age.
AB  - The only inherent and inevitable difference between randomized controlled trials
      and nonrandomized studies (a term that is preferable to "outcomes research") is
      in the allocation of patients to different interventions. Although simple
      interventions, such as drugs, can and should always be evaluated using a
      randomized design, it is often not possible or appropriate to subject more
      complex interventions or policies to that approach. Rather than viewing
      randomized and nonrandomized designs as in competition, they should be seen as
      complementary. One of the major advantages of nonrandomized studies is that they
      can make use of existing large, high quality databases that have been assembled
      for other reasons and therefore provide excellent value-for-money.

PMID- 18622274
TI  - Expanding the evidence base in transplantation: toward a balanced approach.
AB  - The use of a one-dimensional "hierarchy of study designs" to grade the evidence
      on the effectiveness of healthcare interventions is problematic as it may
      underestimate the limitations of randomized controlled trials and overstate those
      of observational studies. Observational studies can be an alternative to
      randomized controlled trials or a source of complementary information. The role
      of observational studies will vary in different situations. Depending on their
      topic, design, and methods of analysis, observational studies may be as credible
      as randomized studies.

PMID- 18622275
TI  - Expanding the evidence base in transplantation: more and better randomized
      trials, and extending the value of observational data.
AB  - Transplant registries, despite being complete and large, will always be
      observational data and subject to potential biases, such as selection bias.
      Consequently conclusions about the effects of interventions will almost always be
      uncertain, except when the magnitude is very large, and natural history of a
      condition homogeneous. Rather than re-running old debates of the outcomes
      research movement, it is time for improvements in registries and randomized
      trials to occur so that effective interventions can be administered to individual
      patients in whom benefits will outweigh harms.

PMID- 18622278
TI  - Pathology of an islet transplant 2 years after transplantation: evidence for a
      nonimmunological loss.
AB  - BACKGROUND: We report the immunological and pathological findings of a 52-year
      old woman, who died two years after the second of two islet transplants performed
      using the Edmonton protocol. After each islet transplant, she gradually lost
      insulin independence while maintaining low levels of C-peptide secretion.
      METHODS: A complete autopsy was performed including pathological and
      immunohistochemical analysis of hepatic allogeneic islets and native pancreatic
      islets to identify rejection or autoimmunity. Elispots assays for allogeneic
      sensitization and autoantibody assays for autoimmunity were performed antemortem
      after her islet transplantations to test in vitro for evidence of allogeneic
      sensitization or autoimmunity. RESULTS: The cause of death was a hypertensive
      stroke. Small numbers of islets without inflammation were identified within
      portal venules and stained with insulin. The atrophic pancreas contained small
      numbers of islets, which stained for insulin, and lacked any inflammation within
      or adjacent to the islets. In vitro assays for alloantibodies were negative, and
      Elispots assays failed to identify allogeneic sensitization. In vitro assays for
      diabetic associated autoantibodies did not identify autoimmune resensitization.
      The allografted kidney showed only early changes of recurrent diabetic
      nephropathy, and no evidence of rejection. CONCLUSIONS: In summary, no evidence
      was found to support an immunological basis (either allo or autoimmunity) for the
      slow loss of intrahepatic islets, which may, therefore, be related to
      nonimmunological anatomic and physiological abnormalities of islets infused into
      the portal veins or to drug toxicity.

PMID- 18622279
TI  - Comparison of short bowel syndrome acquired early in life and during adolescence.
AB  - BACKGROUND: Prolonged survival in pediatric patients with short bowel syndrome
      (SBS) is now possible because of parenteral nutrition and small bowel
      transplantation. We hypothesized that there may be important differences between
      adult patients who developed SBS during early childhood and those who develop
      this as adolescents. METHODS: Sixty-seven patients between the ages of 16 and 40
      years were studied. Thirty patients developing SBS younger than 12 years
      comprised the pediatric group (PG), 37 developing SBS at age 13 to 25 constituted
      the adolescent group (AG). RESULTS: Midgut volvulus (n=11) was the most common
      cause in the PG followed by gastroschisis (n=5), intestinal atresia (n=5), and
      necrotizing enterocolitis (n=4). The most common cause of SBS in the AG was
      trauma (n=13), followed by tumors (n=7) and postoperative complications (n=5). A
      similar portion in each group had intestinal remnants less than 60 cm (69% vs.
      58%), however, the PG was more likely to have a colon remnant (97% vs. 71%,
      P<0.05), and less likely to have an ostomy (7% vs. 47%, P<0.05). Patients in PG
      were followed significantly longer than AG (246+/-67 vs. 90+/-58 months, P<0.05).
      A similar portion of the patients require long-term parenteral nutrition (86% vs.
      84%) or have undergone intestinal transplant (28% vs. 23%). Significantly more
      pediatric patients had negative height z scores when compared with the
      adolescents. CONCLUSIONS: Acknowledging the inherent biases created in defining
      the two groups, pediatric patients developing SBS early in life seem to be
      similar to those who develop SBS as adolescents with regards to long-term
      outcome, despite differences in origin and intestinal anatomy.

PMID- 18622276
TI  - The use of exenatide in islet transplant recipients with chronic allograft
      dysfunction: safety, efficacy, and metabolic effects.
AB  - BACKGROUND: A current limitation of islet transplantation is reduced long-term
      graft function. The glucagon-like peptide-1 receptor agonist, exenatide (Byetta,
      Amylin Pharmaceuticals, CA) has properties that could improve existing islet
      function, prevent further loss of islet mass and possibly even stimulate islet
      regeneration. METHODS: This prospective study evaluated the safety, efficacy, and
      metabolic effects of exenatide in subjects with type 1 diabetes mellitus and
      islet allograft dysfunction requiring exogenous insulin. RESULTS: Sixteen
      subjects commenced exenatide, 12 continue (follow-up 214+/-57 days; range 108
      287), four (25%) discontinued medication because of side effects. At 6 months,
      exogenous insulin was significantly reduced with stable glycemic control (0.15+/
      0.02 vs. 0.11+/-0.025 U/kg per day; P<0.0001); three subjects discontinued
      insulin from 4, 5, and 9 U/day, respectively, two sustained insulin independence
      with A1c reduction below graft dysfunction criteria. Postprandial capillary blood
      glucose was significantly decreased (129.4+/-3.8 vs. 118.7+/-4.6 mg/dL; P<0.001),
      C-peptide and C-peptide-to-glucose ratio increased significantly by 5th and 6th
      months of treatment (ratio, 1.09+/-0.15 vs. 1.52+/-0.18; P<0.05). Weight loss
      more than 3 kg occurred in 8 of 12 (67%) subjects. Stimulation testing
      demonstrated improved glucose disposal and C-peptide secretion (glucose area
      under the curve 52,332+/-3,219 vs. 42,072+/-1,965; P=0.002 mg x min x dL, mixed
      meal stimulation index 0.50+/-0.06 vs. 0.66+/-0.09; P=0.03 pmol x mL), with
      marked suppression of glucagon secretion and progressive increase in amylin
      secretion. Side effects were more frequent and severe compared with published
      reports in type 2 diabetes, tolerated doses were lower. CONCLUSIONS: Exenatide
      was tolerated in this patient population after appropriate dose titration and
      there appeared to be gradual but sustained positive effects on glycemic control
      and islet graft function.

PMID- 18622277
TI  - Anti-proinflammatory effects of sirolimus on human islet preparations.
AB  - BACKGROUND: Sirolimus plays a critical role in facilitating steroid-free
      immunosuppression, in conjunction with low dose tacrolimus, in current islet
      transplantation. Although several studies have investigated the effects of
      sirolimus on islet cells, conflicting results have been reported. In this study,
      we assessed the effects of sirolimus supplementation in culture media on human
      islet preparations, focusing on the anti-proinflammatory aspects. METHODS: Human
      islet preparations were divided into four groups: pure (purity >90%) sirolimus
      (30 ng/mL); pure control (0 ng/mL); impure (purity 40%-60%) sirolimus; and impure
      control. All groups were cultured for 3 days and assessed regarding glucose
      stimulated insulin release, fractional beta-cell viability, beta-cell, and
      macrophage content. Cytokine and chemokine production from islet preparations and
      sorted pancreatic ductal cells were also examined. RESULTS: Stimulated insulin
      release in the impure sirolimus group was significantly increased (P=0.024), as
      previously reported. Although fractional beta-cell viability showed no
      significant differences, beta-cell survival during culture significantly
      increased in impure sirolimus group when compared with the impure control group
      (P=0.015). Tumor necrosis factor-alpha, interleukin-1beta, monocyte chemotactic
      protein-1, and macrophage inflammatory protein-1beta production from the impure
      sirolimus group significantly decreased (P<0.05). Furthermore, tumor necrosis
      factor-alpha and macrophage inflammatory protein-1beta production from sorted
      ductal cells significantly decreased in the sirolimus group (P<0.05). The number
      of macrophages contained in islet preparations significantly decreased in the
      impure sirolimus group when compared with the impure control group (P<0.05).
      CONCLUSIONS: Sirolimus improved not only stimulated insulin release, but also
      beta-cell survival during culture. The antiinflammatory effects of sirolimus also
      appear beneficial to islet cells in culture and may be a useful strategy in
      improving islet transplantation outcomes.

PMID- 18622280
TI  - Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate
      sodium in primary renal transplant recipients given tacrolimus and
      daclizumab/thymoglobulin: one year follow-up.
AB  - BACKGROUND: It was of interest to compare enteric-coated mycophenolate sodium (EC
      MPS) versus mycophenolate mofetil (MMF) among renal transplant recipients
      receiving a tacrolimus-based immunosuppressive regimen. METHODS: Between December
      2004 and February 2006, a single-center, open-label randomized trial of MMF
      (group A, n=75) versus EC-MPS (group B, n=75) was performed in primary renal
      transplant recipients receiving combined thymoglobulin/daclizumab induction along
      with reduced tacrolimus dosing and elimination of corticosteroids 1 week
      postoperatively. The primary endpoint was the incidence rate of acute rejection
      (AR) during the first 12 months posttransplant; secondary aims were to compare
      graft and patient survival, renal function, drug dosing and monitoring,
      gastrointestinal side effects, and other adverse events at 12 months of follow
      up. RESULTS: Patient/graft survival in groups A and B were 100%/96% versus
      99%/96%, respectively (N.S.). At 12 months, a total of nine patients (6%)
      experienced biopsy-proven AR, 3% (2/75) vs. 9% (7/75) in the MMF and EC-MPS arms,
      respectively (N.S.). At 12 months, the geometric mean*/SE serum creatinine
      concentration and arithmetic mean+/-SE calculated glomerular filtration rate in
      groups A and B, respectively, were 1.30*/1.03 and 61.4+/-2.0 vs. 1.26*/1.03 and
      66.0+/-2.1 (N.S.). Incidence of new onset diabetes mellitus (11% vs. 11%),
      infections requiring hospitalization (13% vs. 15%), and gastrointestinal side
      effects (36% vs. 32%) appeared equivalent (N.S.). CONCLUSIONS: Early efficacy and
      toxicity were equivalent between the two study arms. Optimizing either MMF or EC
      MPS along with a combined thymoglobulin/daclizumab induction, low tacrolimus
      dosing and steroid avoidance resulted in a low AR rate and an acceptably high
      renal function at 12 months.

PMID- 18622282
TI  - Fluvastatin in the prevention of renal transplant vasculopathy: results of a
      prospective, randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Statins prevent the progression of transplant vasculopathy in heart
      transplants, but its beneficial effect on the transplanted kidney is
      controversial. METHODS: The aim is to evaluate the utility of fluvastatin 80
      mg/day to reduce the progression of 6-month renal transplant vasculopathy in a
      multicenter, prospective, randomized, placebo-controlled trial stratified
      according to donor age. All patients received cyclosporine, mycophenolate
      mofetil, and prednisone. The progression of transplant vasculopathy was evaluated
      in paired donor and 6-month protocol biopsies. The primary efficacy variable was
      the progression of mean arterial intimal volume fraction (deltaVvintima/artery)
      evaluated with histomorphometry. The minimum sample size to detect a 50%
      reduction in the progression of deltaVvintima/artery was 62 patients per group.
      The secondary efficacy variable included the incidence of transplant vasculopathy
      evaluated according to Banff criteria. RESULTS: A total of 89 patients were
      included, 74 completed the 6-month study and 57 have paired biopsies with
      sufficient tissue for histological evaluation. The deltaVvintima/artery was not
      different between treatment and placebo groups (6.9+/-8.2% vs. 6.9+/-7.4%, P=ns),
      whereas the incidence of transplant vasculopathy was lower in the fluvastatin
      group (7% vs. 33%; P=0.02). Because there was a discrepancy between the primary
      and secondary efficacy variables, post hoc analysis was performed to evaluate the
      reproducibility of both variables in a subset of 50 biopsies. The reproducibility
      of transplant vasculopathy was higher than the reproducibility of Vvintima/artery
      (kappa 0.86 vs. 0.33). CONCLUSIONS: In summary, there were no differences in
      deltaVvintima/artery between groups, but fluvastatin treatment was associated
      with a reduced incidence of transplant vasculopathy.

PMID- 18622281
TI  - H-Y antibody development associates with acute rejection in female patients with
      male kidney transplants.
AB  - BACKGROUND: Human minor histocompatibility antigens (mHA) and clinically relevant
      immune responses to them have not been well defined in organ transplantation. We
      hypothesized that women with male kidney transplants would develop antibodies
      against H-Y, the mHA encoded on the Y-chromosome, in association with graft
      rejection. METHODS: We tested sera from 118 consecutive transplant recipients
      with kidney biopsies. Antibodies that specifically recognized the recombinant H-Y
      antigens RPS4Y1 or DDX3Y were detected by IgG enzyme-linked immunosorbent assay
      and western blotting. Immunogenic epitopes were further identified using
      overlapping H-Y antigen peptides for both the H-Y proteins. RESULTS: In the 26
      female recipients of male kidneys, H-Y antibody development posttransplant (1)
      was more frequent (46%) than in other gender combinations (P<0.001), (2) showed
      strong correlation with acute rejection (P=0.00048), (3) correlated with plasma
      cell infiltrates in biopsied kidneys (P=0.04), and (4) did not correlate with C4d
      deposition or donor-specific anti-human leukocyte antigen (HLA) antibodies. Of
      the two H-Y antigens, RPS4Y1 was more frequently recognized (P=0.005).
      CONCLUSION: This first demonstration of a strong association between H-Y antibody
      development and acute rejection in kidney transplant recipients shows that in
      solid organ allografts, humoral immune responses against well defined mHA have
      clear clinical correlates, can be easily monitored, and warrant study for
      possible effects on long-term graft function.

PMID- 18622283
TI  - Optimizing tacrolimus therapy in the maintenance of renal allografts: 12-month
      results.
AB  - BACKGROUND: The determination of optimal tacrolimus (TAC) trough levels is needed
      to prevent adverse effects of calcineurin inhibitors. METHODS: Stable transplant
      recipients currently receiving cyclosporine (CsA) were assigned randomly (1:1:1)
      to continue CsA (target trough level of 50-250 ng/mL); or convert to "reduced"
      TAC (target trough level 3.0-5.9 ng/mL) or "standard" TAC (target trough level
      6.0-8.9 ng/mL). RESULTS: At 12 months, there was a significant improvement in
      renal function in the reduced TAC versus CsA group with lower serum creatinine
      (P=0.004) and cystatin C (P<0.001), and higher estimated creatinine clearance
      (P=0.017). However, there were no statistically significant differences in any
      renal parameter in the standard TAC versus CsA group. Total and low-density
      lipoprotein cholesterol were significantly reduced in both TAC groups versus the
      CsA group (P<0.001). Patient and graft survival and episodes of biopsy-confirmed
      acute rejection were similar for all treatment groups, and no statistically
      significant differences were observed between groups in the incidence of new
      onset diabetes or cardiac conditions, or in the prevalence of hyperglycemia,
      hypertension, or hyperlipidemia among patients who did not have these conditions
      at baseline. Alopecia developed more commonly among TAC-treated patients than CsA
      treated patients (P<0.001). CONCLUSIONS: Compared with CsA continuation,
      conversion to reduced TAC target trough concentrations resulted in significantly
      improved renal function without increasing the risk of rejection. Conversion to
      TAC, regardless of target concentration, resulted in improved serum lipid
      profiles in kidney transplant recipients at 12 months.

PMID- 18622284
TI  - Renal transplantation in patients with positive lymphocytotoxicity crossmatches:
      one center's experience.
AB  - BACKGROUND: Sensitization to human leukocyte antigens remains an important
      barrier to successful renal transplantation. MATERIALS AND METHODS: Herein we
      describe our center's experience with a plasmapheresis-based desensitization
      protocol for highly sensitized patients. Twenty-nine patients had a positive T
      cell or positive B-cell lymphocytotoxicity crossmatch against their donors. In
      some cases, baseline crossmatches were of high titer (e.g., 11 had baseline
      titers > or =1:32). RESULTS: Twenty-eight of 29 patients were rendered T-cell
      crossmatch negative and B-cell crossmatch negative/low positive and transplanted.
      None had hyperacute rejection but 11 (39%) had acute antibody mediated rejection.
      Median follow-up is 22 months: 25 of the 28 (89%) of allografts are still
      functioning with mean plasma creatinine 1.5 mg/dL. There was one death because of
      the transplant or immunsuppression, one case of cytomegalovirus disease and no
      cases of lymphoproliferative disease. CONCLUSION: This series provides further
      evidence of the high efficacy of plasmapheresis-based desensitization protocols.
      Even patients with high baseline crossmatch titers can be successfully
      desensitized and transplanted. Short- and medium-term outcomes are encouraging
      but longer-term data are needed.

PMID- 18622285
TI  - Liver transplantation trends for older recipients: regional and ethnic
      variations.
AB  - BACKGROUND: Liver transplantation (LT) provides long-term survival for adults
      with end-stage liver disease. As a result of improved survival and an aging
      United States population the demand for LT in older patients is expected to
      increase. The aim of this study was to describe the transplantation trends in the
      older recipient (older than 65 years). METHODS: Using the United Network for
      Organ Sharing database, we identified LT recipients between 1990 and 2006. We
      used Kaplan-Meier method to calculate overall survival (1, 3, 5 and 10 years) and
      Cox regression for predictors of survival. RESULTS: During the study period 5630
      (7.6%) LT recipients were older than 65 years. There were 4256 (79.4%) whites,
      Hispanic (10.3%), African Americans (AA) (3.6%), and rest (6.7%). There was an
      increase in LT for older than 65 years from 4.1% in 1990 to 10.2% in 2006
      (P=0.002) and a regional variation (P<0.001). The 10-year patient and graft
      survival was 60% and 57% for less than 65 years versus 42% and 40% for more than
      65 years (P<0.0001). With age stratification (65-75 years vs. >75 years), there
      was no difference in survival but when adjusted for race there was a significant
      difference in graft survival with a 10 year (white 40%, Hispanic 44%, and AA 19%)
      (P=0.04). CONCLUSION: The demand for LT in recipients older than 65 years is
      increasing. Although their survival is lower in comparison with recipients less
      than 65 years, there seems to be no difference in unadjusted survival with age
      stratification above 65 years. Among ethnic minorities, there was a
      disproportionately lower percentage of African Americans LT and a decreased
      survival.

PMID- 18622286
TI  - Chronic kidney disease--a common and serious complication after intestinal
      transplantation.
AB  - BACKGROUND: Chronic kidney disease after organ transplantation is a serious
      complication that negatively impacts on long-term patient survival. We describe
      long-term renal function after intestinal transplantation by serial measurements
      of glomerular filtration rates (GFR) with Chromium EDTA clearance. MATERIALS AND
      METHODS: Ten patients with at least 6 months survival form the basis of this
      report. Glomerular filtration rate measurements were performed at baseline, 3
      months posttransplantation, and yearly thereafter. Median follow-up time for the
      cohort was 1.5 years (0.5-7.8 years). Tacrolimus (Prograf) was discontinued in
      four patients because of impaired renal function. These four patients were
      switched to sirolimus (Rapamune) at 11, 18, 24, and 40 months
      posttransplantation. RESULTS: Median baseline GFR was 67 (22-114) mL/min/1.73 m.
      In the adult patients, GFR 3 months posttransplantation had decreased to 50% of
      the baseline. At 1 year, median GFR in the adult patients was reduced by 72%
      (n=5). Two patients developed renal failure within the first year and required
      hemodialysis. One of the pediatric patients fully recovered her renal function,
      the second pediatric patient lost 20% of her baseline GFR at 6 months
      posttransplantation. Glomerular filtration rate calculated with the modified diet
      in renal disease formula consistently overestimated GFR by approximately 30%
      compared with measured GFR. CONCLUSION: Chronic kidney disease and renal failure
      are common after intestinal transplantation. These two factors significantly
      contribute to poor long-term survival rates. Measurements of GFR may help to
      identify those individuals at risk for developing chronic kidney disease to
      implement renal sparing strategies.

PMID- 18622287
TI  - Safe inclusion of the entire pancreas as a component of the multivisceral graft.
AB  - BACKGROUND: Multivisceral transplantation (MVtx) involves simultaneous
      transplantation of the intestine with other organs, often including the pancreas.
      The pancreas portion of the graft has always been approached with caution because
      allograft pancreatitis, rejection or technical complications may be devastating
      in this setting. We reviewed our experience with multivisceral grafts that
      included the entire pancreas. METHODS: Twenty-five patients received 27 MVtx that
      included the entire pancreas between July 2003 and November 2006. In five, a
      modified MVtx with preservation of the native liver was performed. Two patients
      required retransplantation for severe rejection. Insulin requirements, graft and
      patient survival were determined at 6-months posttransplant. Serum amylase and
      lipase levels were analyzed on postoperative days 3, 7, 30, and 180. RESULTS:
      Twenty of 25 patients with a transplant pancreas graft were alive at 6-months
      posttransplant. Median serum amylase and lipase levels posttransplant were normal
      at all time points. One patient exhibited elevation of amylase and lipase at the
      time of severe acute cellular rejection of the intestinal graft, likely
      representing simultaneous pancreas allograft rejection, although this was not
      confirmed by biopsy. There were no episodes of allograft pancreatitis or
      technical complications. Once weaned from hyperalimentation, all patients
      remained normoglycemic and insulin-independent 6-months posttransplant.
      CONCLUSION: In this series, there were no postoperative pancreatic complications,
      no episode of isolated pancreas allograft rejection, and no loss of pancreatic
      graft function. None of the five deaths were related to pancreatic graft
      complications.

PMID- 18622288
TI  - Renal function impacts outcomes after intestinal transplantation.
AB  - BACKGROUND: Although renal dysfunction (RD) has been commonly associated with
      poor outcome after other solid organ transplants, it has not been studied in
      detail after intestinal transplantation (ITx). Here we provide a detailed
      analysis of renal function after ITx, and identify predictors of post-ITx RD.
      METHODS: A retrospective analysis of patients undergoing ITx from 1991 to 2006
      was performed. For each patient, the estimated glomerular filtration rate (eGFR)
      was compared with the normal GFR for age and gender to obtain the percent of
      normal eGFR. Chi-square analysis and log-rank tests were used to identify
      categorical variables associated with RD (eGFR <75% of normal) and to determine
      if RD was predictive of post-ITx survival. RESULTS: Sixty-eight transplantations
      were performed in 62 patients. Overall patient survival at 1 and 5 years was 78%
      and 56%, respectively. Renal dysfunction was observed in 16% of patients post
      ITx. The most frequent predictors of post-ITx RD were preoperative eGFR less than
      75% of normal, pre-ITx location in the intensive care unit, and high-dose
      tacrolimus immunotherapy. An eGFR less than 75% of normal at days 7, 28, and 365
      was predictive of poor patient survival (P<0.05). CONCLUSIONS: This study
      provides the first detailed analysis of renal function after ITx. We identified
      specific risk factors for the development of RD in the first year post-ITx and
      found a significant association of RD with decreased long-term survival. Given
      the strong correlation of RD with poor outcome, preserving renal function may be
      key to improving long-term outcomes in ITx recipients.

PMID- 18622289
TI  - C4d deposition and cellular infiltrates as markers of acute rejection in rat
      models of orthotopic lung transplantation.
AB  - BACKGROUND: C4d is a useful marker of antibody-mediated rejection in cardiac and
      renal transplants, but clinical studies examining correlations between
      circulating alloantibodies, C4d deposition, and rejection in lung transplants
      have yielded conflicting results. METHODS: We studied circulating alloantibody
      levels and C4d deposition in two rat models of lung transplantation: Brown Norway
      (BN) to Wistar-Kyoto (WKY) and PVG.R8 to PVG.1U lung allografts. The availability
      of C6 deficient (C6-) and C6 sufficient (C6+) PVG 1U rats allowed evaluation of
      the effects of the terminal complement components on graft injury and C4d
      deposition. RESULTS: The lung allografts had histologic features resembling human
      posttransplant capillaritis, characterized by neutrophilic infiltration of
      alveoli, edema, and hemorrhage. Immunoperoxidase stains on cross sections of
      allografts showed intense, diffuse, C4d deposition in a continuous linear pattern
      on the vascular endothelium. C4d deposits were found in both BN to WKY and PVG R8
      to 1U allografts, whereas no staining was detectable in WKY to WKY isografts or
      native lungs. Complement deposition was associated with vascular disruption in
      C6+, but not in C6- recipients. The presence of circulating donor-specific
      alloantibodies was verified by flow cytometry. Cell-specific staining revealed
      perivascular accumulation of macrophages and T lymphocytes whereas neutrophils
      were sequestered in the intravascular and alveolar capillary compartments.
      CONCLUSIONS: The deposition of C4d on vascular endothelium as well as the
      coincident presence of alloantibodies is consistent with previous findings in
      antibody-mediated rejection of renal and cardiac transplants. Furthermore, the
      histological features of our allografts support the concept that posttransplant
      capillaritis is a form of humoral rejection.

PMID- 18622290
TI  - Contrasted blood and intragraft toll-like receptor 4 mRNA profiles in operational
      tolerance versus chronic rejection in kidney transplant recipients.
AB  - BACKGROUND: Deciphering the mechanisms of tolerance and chronic rejection (CR)
      remains a major goal in transplantation. Data in rodents suggest that Toll-like
      receptors (TLR), regulators of innate immune responses, play a role in
      determining graft outcome. However, few studies have focused on TLR expression in
      human kidney transplant recipients. METHODS: Here, we analyzed the expression of
      TLR4 in peripheral blood mononuclear cells from kidney recipients with contrasted
      clinical situations: operational tolerance and CR, compared with patients with
      stable graft function, nontransplant patients with renal failure and healthy
      volunteers. RESULTS: We report that myeloid differentiation factor 88 and TLR4
      are significantly contrasted in the peripheral blood mononuclear cells, and in
      particular in monocytes, of patients with CR versus operational tolerance.
      Chronic rejection patients have significantly increased TLR4 and myeloid
      differentiation factor 88 compared with operationally tolerant patients, who
      resemble healthy volunteers and nontransplant patients with renal failure.
      Interestingly, analysis of TLR4 transcripts in graft biopsies from patients with
      normal histology or CR reflected the blood findings, with a significant increase
      of TLR4 in CR. CONCLUSIONS: These data support a link between TLR4 expression and
      long-term graft outcome. Moreover, whereas absence of TLR signaling may be a
      feature of tolerance, increased TLR4 signaling may be implicated in CR.

PMID- 18622291
TI  - Prolongation of cardiac and islet allograft survival by a blocking hamster anti
      mouse CXCR3 monoclonal antibody.
AB  - BACKGROUND: Acute allograft rejection requires a multifaceted immune response
      involving trafficking of immune cells into the transplant and expression of
      effector cell functions leading to graft destruction. The chemokine receptor
      CXCR3 and its ligands, CXCL9, CXCL10 and CXCL11, constitute an important pathway
      for effector cell recruitment posttransplant. However, analysis of CXCR3
      expression and function has been hampered by a general lack of availability of a
      neutralizing anti-CXCR3 monoclonal antibody (mAb) for use in experimental models.
      METHODS: We report the generation, characterization, and use of CXCR3-173, a new
      hamster mAb specific for mouse CXCR3 that recognizes CXCR3 on cells from wild
      type but not CXCR3-/- mice. RESULTS: Using CXCR3-173 mAb, we demonstrate CXCR3
      expression on primary memory phenotype CD4+ and CD8+ T cells, naturally occurring
      CD4+CD25+ Foxp3+ regulatory T cells, natural killer T cells, and approximately
      25% of NK cells. CXCR3-173 blocked chemotaxis in vitro in response to CXCL10 or
      CXCL11 but not CXCL9. When injected into mice, this mAb significantly prolonged
      both cardiac and islet allograft survival. When combined with a subtherapeutic
      regimen of rapamycin, CXCR3-173 mAb induced long-term (>100 day) survival of
      cardiac and islet allografts. The in vivo effects of CXCR3-173 mAb were not
      associated with effector lymphocyte depletion. CONCLUSION: These data highlight
      the utility of CXCR3-173 mAb in developing immunotherapeutic approaches to
      inhibit transplant rejection and potentially other immune-mediated diseases in
      murine models.

PMID- 18622292
TI  - Brain death induces inflammation in the donor intestine.
AB  - BACKGROUND: Brain death donors are frequently used for transplantation. Previous
      studies showed that brain death (BD) negatively affects the immunological and
      inflammatory status of both liver and kidney. Because the intestine is
      increasingly used as a donor organ and no information on effects of BD on small
      intestine is available we performed this study. METHODS: We studied the
      inflammatory and apoptotic changes in donor intestine after BD induction. Brain
      death was induced in rats by inflation of a balloon catheter. Three groups (n=6)
      were compared: 1-hr BD, 4-hr BD, and sham-operated controls. RESULTS: An
      increased polymorphonuclear cell influx in ileum, as a measure of inflammation,
      was observed in 1- and 4-hr BD group compared with controls. Jejunum showed a
      significant increase at the 4-hr BD group compared with the control group.
      Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin,
      and interleukin-6 were upregulated after 1- and 4-hr BD. Caspase-3 positive cells
      were found in jejunum and ileum after 4-hr BD on the top of the villi. Serum
      interleukin-6 was severely elevated in the 1- and 4-hr brain dead rats.
      CONCLUSION: These data show the early occurrence of intestinal inflammation and
      apoptosis after BD induction. These events may ultimately have a negative
      influence on the outcome of intestinal transplantation.

PMID- 18622293
TI  - Human fibroblasts are permissive for porcine cytomegalovirus in vitro.
AB  - BACKGROUND: Xenotransplantation with pig organs is being considered to alleviate
      donor organ shortages; however, the risk of introducing porcine viruses into
      humans is heightened in this setting. The goal of this study was to determine the
      infectious potential of porcine cytomegalovirus (PCMV), a xenozoonotic virus of
      interest, in human fibroblasts in vitro. METHODS: Confluent human cells were
      incubated with live PCMV, heat-killed PCMV, or medium alone. Infection was
      investigated by testing for viral-induced cytopathic effect, assaying viral
      transcription by nested RT-PCR and subsequent sequencing, and detecting viral
      protein expression by Western blotting. Plaque neutralization experiments were
      also performed. RESULTS: Cells incubated with PCMV demonstrated significant
      cytopathic effect by 7 days postinfection, and reverse-transcriptase polymerase
      chain reaction sequencing identified PCMV DNA polymerase in these infected cells.
      In Western blots, monoclonal antibodies (mAbs) to human CMV glycoprotein B and
      pig serum presumed to contain anti-PCMV antibodies detected characteristic
      proteins in experimentally infected human cells and positive controls but not in
      negative controls. Furthermore, one of these mAbs and the pig serum neutralized
      PCMV infection in vitro. CONCLUSIONS: These results are a first demonstration
      that PCMV can infect human fibroblasts in vitro.

PMID- 18622294
TI  - Prophylaxis followed by preemptive therapy versus preemptive therapy for
      prevention of human cytomegalovirus disease in pediatric patients undergoing
      liver transplantation.
AB  - Twenty-one pediatric liver transplant recipients were enrolled in a study
      comparing prophylaxis followed by preemptive therapy (10 patients) versus
      preemptive therapy alone (11 patients) for prevention of human cytomegalovirus
      (HCMV) disease. In the prophylaxis arm, patients were treated with ganciclovir
      for 30 days, then preemptive therapy was initiated with virologic monitoring for
      pp65 antigenemia. In the preemptive therapy arm, patients were treated on
      reaching 100,000 DNA copies/mL whole blood. An interim analysis showed that,
      although numbers of both infected and treated patients were comparable in the two
      arms, the median number of total days of antiviral therapy per patient (30 vs.
      18, P<0.01) was significantly higher in the prophylaxis arm. No case of HCMV
      disease occurred in either arm. Therefore, the trial was interrupted and
      prophylaxis replaced with preemptive therapy alone. In parallel, the development
      of T-cell-mediated immune response was found to be comparable in both arms.

PMID- 18622295
TI  - Therapeutic effects of hepatocyte transplantation on hemophilia B.
AB  - Hepatocyte transplantation offers an alternative therapeutic approach in the
      treatment of liver-related diseases. Hemophilia B is a bleeding disorder lacking
      factor IX (FIX) production in the liver, and achieving more than 1% coagulation
      activity results in significant improvement in the quality of life of the
      patients. The aim of this study was to investigate the efficacy of hepatocyte
      transplantation in the mouse model of hemophilia B. We transplanted isolated
      normal mouse hepatocytes into the liver of FIX knock-out mice. In some recipient
      mice, additional hepatocyte transplantations were performed 15 days after the
      first transplant. The recipient plasma FIX activities increased at 1% to 2% and
      persisted throughout the experimental period. An additional increase was achieved
      by the repeated transplantation. Close correlation between FIX messenger RNA
      levels of the liver and plasma FIX activity levels was observed. These results
      demonstrate that hepatocyte transplantation can provide therapeutic benefits in
      the treatment of hemophilia B.

PMID- 18622296
TI  - Efficacy of a nanocochleate-encapsulated 3,5-diaryl-s-triazole derivative in a
      murine model of graft-versus-host disease.
AB  - We have previously demonstrated that the compound 3-(2-ethylphenyl)-5-(3
      methoxyphenyl)-1H-1,2,4-triazole exerts immunosuppressive effects in several
      experimental models of autoimmunity. These results were achieved by
      subcutaneously administering ST1959 after dissolution in an oily vehicle, because
      of its poor water solubility. To circumvent this problem, we sought to determine
      whether nanocochleate technology could be successfully exploited to deliver
      ST1959 and protect mice undergoing lethal acute graft-versus-host disease (GVHD).
      Orally-administered encochleated ST1959 significantly protected animals from
      lethality, resulting in survival rates of 57% and 100% at doses of 2 and 10
      mg/kg, respectively, whereas oral administration of 2 mg/kg ST1959, mixed with
      empty nanocochleates, was completely inactive. Increased survival was associated
      with diminished serum chemokine levels and donor CD8+ T cells in the spleen of
      ST1959-treated mice. Moreover, ST1959 treatment significantly counteracted GVHD
      induced normocitic anemia by increasing hemoglobin, hematocrit, platelet, and red
      and white blood cell counts. Overall, these data show that orally-administered
      encochleated ST1959 significantly protects mice from GVHD.

PMID- 18622297
TI  - ABO incompatible renal transplantation in an HIV-seropositive patient.
AB  - To date, there have been no reports of successful ABO blood group incompatible
      renal transplantation in HIV patients. We describe a case of a 47-year-old
      African American man with end-stage renal disease secondary to HIV-induced
      nephropathy who underwent a live unrelated (spouse) donor ABO blood group
      incompatible transplant using an intravenous immunoglobulin/plasmapheresis
      preconditioning regimen with interleukin-2 receptor antagonist induction along
      with tacrolimus and mycophenolate mofetil maintenance. The postoperative course
      was complicated by two acute cellular rejection (Banff Ia) episodes that were
      successfully managed with corticosteroid boluses and the addition of
      corticosteroids to maintenance immunosuppression. Antibody-mediated rejection was
      not observed on biopsy. The patient reached a serum creatinine nadir of 2.0 mg/dL
      on postoperative day 20, which has now been maintained for 170 days. His current
      CD4 count was 410 cells/microL.

PMID- 18622298
TI  - Refractory graft versus host disease after pediatric intestinal transplantation
      beware of pre-existing immunodeficiency.

PMID- 18622299
TI  - Sirolimus (rapamycin) induced proteinuria in a patient undergoing allogeneic
      hematopoietic stem cell transplant.

PMID- 18622300
TI  - Global coding system for human cells and tissues for transplantation.

PMID- 18622302
TI  - Prospective comparative study on the acceptability of unsedated transnasal
      endoscopy in younger versus older patients.
AB  - GOALS: The aim of this prospective study was to compare the acceptance and
      tolerance for unsedated transnasal esophagogastroduodenoscopy (EGD) between
      younger and older patients. BACKGROUND: Little information is available on
      comparisons of younger and older patients with regard to acceptance and tolerance
      of transnasal EGD. STUDY: A total of 260 patients were referred for unsedated
      transnasal EGD and divided into 2 groups according to their age: less than 60
      years of age (group A, n=160) and 60 years of age and older (group B, n=100). A
      questionnaire for tolerance was completed by each patient (a validated 0 to 10
      scale where "0" represents no discomfort/well tolerated and "10" represents
      severe discomfort/poorly tolerated). RESULTS: In 94.4% of group A and 95.0% of
      group B, insertions were successfully completed (P>0.05). Between groups A and B,
      discomfort during nasal anesthesia (1.7+/-0.2 vs. 1.6+/-0.2) and overall
      tolerance during procedure (1.7+/-0.2 vs. 1.5+/-0.2) were similar (P>0.05).
      However, discomfort during insertion was significantly greater in group A than in
      group B (2.5+/-0.2 vs. 1.9+/-0.2, P=0.02). Of all, 97.4% of group A and 94.7% of
      group B were willing to undergo unsedated transnasal EGD in the future (P>0.05).
      CONCLUSIONS: There was no significant difference in acceptability between younger
      and older patients for unsedated transnasal EGD. Otherwise, younger patients
      experienced significantly more discomfort during insertion than did older
      patients.

PMID- 18622301
TI  - Interaction between income and education in predicting long-term survival after
      acute myocardial infarction.
AB  - BACKGROUND: Population-based data on the impact of socioeconomic status (SES) on
      long-term survival after myocardial infarction (MI) are lacking. We evaluated the
      association of income and education with all-cause mortality and cardiac
      mortality post-MI and assessed income-by-education interaction. DESIGN:
      Prospective cohort study. METHODS: Between February 1992 and February 1993, 1,521
      consecutive patients aged 65 years or less (19% women) discharged from all
      hospitals in central Israel after incident acute MI were enrolled and followed up
      through December 2005. Data on SES indicators, cardiovascular risk factors, MI
      characteristics and severity, comorbidities, and acute treatment were assessed at
      baseline. RESULTS: Low SES, as defined by income and education, was associated
      with older age, female sex, and higher prevalence of risk factors and
      comorbidities. Further, low SES patients presented with more severe disease and
      received fewer cardiac procedures and medications. During follow-up, 427 patients
      died. Income and education strongly interacted (P=0.003). The hazard ratio for
      death associated with income (below average vs. average/above average) was
      considerably higher for less educated (<12 years) patients [2.64, 95% confidence
      interval (CI): 1.92-3.63] than for more educated (>or=12 years) patients (1.53,
      95% CI: 1.02-2.29). Adjustment for various prognostic indicators attenuated these
      estimates, yet excess risk persisted for the less educated group (hazard
      ratio=1.58, 95% CI: 1.13-2.21). Similar patterns were noted for cardiac
      mortality. CONCLUSION: Among patients with incident MI, low SES is related to
      higher risk profile and poorer treatment. Low income is associated with a large
      increase in mortality risk when accompanied by low education, suggesting a double
      jeopardy phenomenon.

PMID- 18622303
TI  - Elevated sex hormone binding globulin levels may contribute to sexual dysfunction
      in men with chronic hepatitis C virus infection.

PMID- 18622304
TI  - Problems with combining together EGD, PEG, flexible sigmoidoscopy, and
      colonoscopy to analyze risks of endoscopic procedures after MI: a call for
      stratifying risk according to individual endoscopic procedures.

PMID- 18622305
TI  - In reference to Sleep medicine for surgeons.

PMID- 18622307
TI  - A clinical classification system for aberrant internal carotid arteries.
AB  - OBJECTIVES/HYPOTHESIS: Pronounced anatomic variations of the extracranial
      internal carotid artery (ICA) can be found in 5% to 6% of the general population.
      An aberrant ICA is at risk of injury during routine pharyngeal procedures if the
      vessel is placed into close relationship with the pharyngeal wall. The objective
      was to highlight the impact of parapharyngeal ICA aberrations and to analyze the
      clinical usefulness of the current anatomic classification system of these
      anomalies. STUDY DESIGN: Prospective quality assessment study in an academic
      tertiary care medical center. METHODS: A systematic clinicoradiological follow-up
      study was performed over a period of 18 months. The ICA's course was classified
      according to Weibel and Fields in 21 consecutive patients with 35 pronounced
      parapharyngeal ICA aberrations. The vessels' minimum distance to the pharyngeal
      wall and the corresponding pharyngeal level was analyzed. RESULTS: Tortuosity was
      found in 13, kinking in 18, and coiling in 4 aberrant ICAs. The vessel's minimum
      distance to the pharyngeal wall ranged from 0.8 to 17.9 mm (mean, 7.0 mm), but
      the currently used anatomic classification was inadequate to determine the risk
      potential for ICA injury in the given cases. We propose a clinicoradiological
      classification system, which considers the vessel's relation to the pharyngeal
      wall. CONCLUSIONS: Parapharyngeal ICA aberrations are common and probably under
      appreciated anatomic variations. The awareness of these anomalies is essential
      for clinicians. Since the current anatomic classification is insufficient to
      outline patients with an increased risk of ICA injury, a clinicoradiological
      graduation of cervical ICA aberrations may be of practical benefit.

PMID- 18622306
TI  - A genomewide screen for chronic rhinosinusitis genes identifies a locus on
      chromosome 7q.
AB  - OBJECTIVE/HYPOTHESIS: Chronic rhinosinusitis (CRS) is an important public health
      problem with substantial impact on patient quality of life and health care costs.
      We hypothesized that genetic variation may be one factor that affects this
      disease. STUDY DESIGN: Identification of genetic variation underlying
      susceptibility to CRS using linkage analysis in a founder population. METHODS: We
      studied a religious isolate that practices a communal lifestyle and shares common
      environmental exposures. Using physical examination, medical interviews, and a
      review of medical records, we identified eight individuals with CRS of 291
      screened. These eight individuals were related to each other in a single 60
      member, nine generation pedigree. A genome-wide screen for loci influencing
      susceptibility to CRS using 1123 genome-wide markers was conducted. RESULTS: The
      largest linkage peak (P = .0023; 127.15 cM, equivalent to limit of detection =
      2.01) was on chromosome 7q31.1-7q32.1, 7q31 (127.15 cM; 1-limit of detection
      support region: 115-135 cM) and included the CFTR locus. Genotyping of 38
      mutations in the CFTR gene did not reveal variation accounting for this linkage
      signal. CONCLUSIONS: Understanding the genes involved in CRS may lead to
      improvements in its diagnosis and treatment. Our results represent the first
      genome-wide screen for CRS and suggest that a locus on 7q31.1-7q32.1 influences
      disease susceptibility. This may be the CFTR gene or another nearby locus.

PMID- 18622308
TI  - Aerodynamic changes as a result of vocal function exercises in elderly men.
AB  - OBJECTIVES/HYPOTHESIS: Voice therapy can improve the vocal quality of elderly
      patients with voice problems, but the changes in vocal aerodynamics associated
      with physiologic voice therapy are not well documented. The purpose of the
      present study was to determine the changes in vocal aerodynamics as a result of
      the management program known as Vocal Function Exercises (VFEs). STUDY DESIGN:
      Pre- and post-treatment differences in VFE maximum phonation times (MPT) and
      measures of vocal aerodynamics were analyzed. METHODS: There were 19
      participants, aged 60 to 78 years, who performed VFEs twice a day for 12 weeks.
      Aerodynamic measures of glottal airflow and subglottic pressure were collected at
      comfortable, high, and low pitches both before the initiation of the exercise
      program and again at its conclusion. MPT data were collected weekly. RESULTS: The
      participants showed continuous improvement in VFE MPT across the 12 weeks.
      Significant differences occurred from pre- to post-therapy on some measures of
      vocal aerodynamics relating to glottic closure. CONCLUSIONS: Decrease in glottic
      airflow was achieved, with a concomitant increase in subglottic pressure, but
      without an increase in acoustic power (comfortable and low pitch). Improvement in
      VFE MPT mirrored the improvement in vocal aerodynamics.

PMID- 18622309
TI  - Chondrosarcomas of the jugular foramen.
AB  - OBJECTIVES/HYPOTHESIS: Chondrosarcomas of the jugular foramen are extremely rare
      tumors. Our review of the literature revealed eleven previously reported cases.
      The aim of this study is to describe the presenting symptoms, radiographic
      findings, operative procedures, and postoperative outcome of five histologically
      confirmed cases of chondrosarcomas arising from the jugular foramen. A review of
      the literature is also presented. STUDY DESIGN: Retrospective study of an
      quaternary referral otology and skull base private center. METHODS: Five cases of
      surgically treated and pathologically confirmed jugular foramen chondrosarcomas
      were identified. The follow-up of the series ranged from 23 to 42 months (mean,
      32.8 +/- 7.7 months). RESULTS: A single stage procedure was adopted in all the
      cases. Two patients underwent type A infratemporal approaches, one patient
      underwent a transotic approach extending to the neck with ligature of the
      internal jugular vein, one patient underwent a petro-occipital transigmoid
      approach, and one patient underwent a combined petro-occipital transigmoid
      transotic approach. Gross total tumor removal was achieved in all patients. The
      most common complications were lower cranial nerve deficits. To date, no
      recurrence or residual tumors have been observed at radiological controls.
      CONCLUSIONS: We believe that the primary treatment for chondrosarcomas of the
      jugular foramen is gross total surgical resection of the tumor. It is our
      philosophy to reserve postoperative radiotherapy for patients with histologically
      aggressive tumors, as well as in cases with subtotal resection and recurrent
      tumors.

PMID- 18622310
TI  - Narrow band imaging for detecting metachronous superficial oropharyngeal and
      hypopharyngeal squamous cell carcinomas after chemoradiotherapy for head and neck
      cancers.
AB  - We present two cases of metachronous superficial squamous cell carcinomas at
      oropharyngeal and hypopharyngeal mucosal sites after chemoradiotherapy for head
      and neck cancers. These were detected by narrow band imaging combined with a
      magnifying gastrointestinal endoscopy. In one case, we successfully removed the
      tumor using endoscopic submucosal dissection. Narrow band imaging combined with
      magnifying gastrointestinal endoscopy illustrated well-demarcated brownish area
      and scattered foci of microvascular proliferation. Thus, it may serve as an ideal
      surveillance mode after chemoradiotherapy for head and neck cancers.

PMID- 18622311
TI  - Down-regulation of carbonic anhydrase isoenzymes in nasal polyps.
AB  - OBJECTIVES/HYPOTHESIS: Carbonic anhydrase (CA) is a zinc metalloenzyme that
      participate in the biological processes of various fluid transporting epithelia,
      including ion and water transport. CA may thus play a role in the pathophysiology
      of normal nasal mucosa and nasal polyp. We evaluated the expression and pattern
      of distribution of mRNAs and proteins for CA isoenzymes in normal nasal mucosa
      and polyps. STUDY DESIGN: This was a controlled, prospective study. METHODS: The
      expression levels of 11 isoenzyme genes (I, II, III, IV, VA, VB, VI, VII, IX,
      XII, XIV) were evaluated in normal mucosa and polyps using semiquantitative
      reverse-transcriptase polymerase chain reaction. The expression and pattern of
      distribution of CA I, II, and IX were also investigated using
      immunohistochemistry and Western blot. RESULTS: mRNAs for the 11 CA isoenzymes
      were detected in all normal nasal mucosa and polyps tested. Their expression
      levels were decreased in nasal polyp in comparison with normal nasal mucosa. CA I
      was detected in the epithelial cells, endothelial cells, and submucosal gland of
      normal nasal mucosa, but only in the endothelial cells in nasal polyp. CA II in
      normal mucosa was intensely expressed in the submucosal gland cells and CA IX was
      noted in the cytoplasm and plasma membrane of epithelial cells and submucosal
      glands. However, these findings were not found in nasal polyp. Western blot also
      showed differences in their expression levels. CONCLUSIONS: These results
      indicate that CA may participate in the physiology of normal nasal mucosa, but
      also suggest that altered their expression in nasal polyps may cause impaired
      electrolyte and water transport across the epithelial cells.

PMID- 18622312
TI  - Pre-Baha operation three dimensional computed tomography with markers for
      determining optimal implant site.

PMID- 18622313
TI  - Reconstruction of the internal nasal valve: modified splay graft technique with
      endonasal approach.
AB  - OBJECTIVE/HYPOTHESIS: The aim of this study was to determine the reliability and
      feasibility of modified splay graft technique in the surgical correction of
      internal nasal valve (INV) incompetence and nasal valve collapse. STUDY DESIGN:
      Eleven patients operated with the diagnosis of INV incompetence were followed for
      6 to 30 months after operation. METHODS: Between 2004 and 2007, 11 patients with
      the complaint of shortness of breath, and in whom nasal valve incompetence was
      detected, and who were positive for Cottle and modified Cottle tests were
      operated. In the operation, splay graft was used endonasally with the technique
      we describe. Before and at least 6 months after the operation, patients were
      evaluated with acoustic rhinometry, linear symptom scale, and nasal obstruction
      symptom evaluation scale in addition to endoscopic examination, and the results
      were compared. RESULTS: In 10 of 11 (90.9%) patients operated with modified splay
      graft technique, marked improvement was observed in INV region with endoscopic
      examination and acoustic rhinometry. In the evaluation made with linear symptom
      scale and nasal obstruction symptom evaluation scale, partial improvement was
      seen in nasal obstruction in one patient and marked improvement in 10 patients.
      No complications developed. CONCLUSIONS: Modified splay technique is an effective
      graft method that can be easily applied and has minimal complications and
      morbidity.

PMID- 18622314
TI  - Superior canal dehiscence plugging reduces dizziness handicap.
AB  - OBJECTIVES/HYPOTHESIS: To compare dizziness handicap inventory (DHI) scores
      before and after surgery for plugging of superior canal dehiscence (SCD). The
      size of the dehiscence as measured during surgery, subject age, vestibular-evoked
      myogenic potentials threshold, and degree of conductive hearing loss (CHL) were
      also considered. STUDY DESIGN: Retrospective. METHODS: Nineteen adults with SCD
      who underwent surgery to plug the SCD via middle fossa approach were studied. Pre
      and postoperative DHI scores were compared, and correlations between DHI scores
      and other clinical measures were assessed. RESULTS: Average preoperative DHI
      score was 44 +/- 24 (mean +/- SD). Postoperative DHI score was significantly
      lower at 18 +/- 15 (P < .01). Only two subjects had a higher DHI score after
      surgery. Subjects who had a preoperative DHI score below 30 did not have any
      significant change in their DHI score after surgery, whereas those with a
      preoperative DHI score >or=30 had an improvement by an average of 39 +/- 16 after
      surgery. There were no correlations between either preoperative DHI score or the
      change in DHI score after surgery and HL, age, vestibular-evoked myogenic
      potentials threshold, or dehiscence size. CONCLUSIONS: DHI scores significantly
      decreased after SCD plugging. Subjects who had the largest decrease in DHI scores
      were those with high preoperative DHI scores. Subjects who chose to undergo SCD
      plugging because of nonvestibular symptoms such as conductive HL, tinnitus, or
      autophony generally had lower preoperative DHI scores and did not experience
      large improvements in DHI scores. The SCD plugging procedure offers an
      improvement in DHI score that is comparable with that of other procedures for
      peripheral vestibular dysfunction.

PMID- 18622315
TI  - Platelet-rich plasma for pediatric tonsillectomy patients.
AB  - OBJECTIVES/HYPOTHESIS: To determine if placement of autologous platelet-rich
      plasma (PRP) on the tonsil beds at the time of tonsillectomy would decrease
      postoperative pain and complications. STUDY DESIGN: Double blind, randomized,
      prospective study. METHODS: Seventy children were recruited to participate in the
      study, ranging in age from 4 to 15 years. They were randomized to treatment (PRP)
      or control groups. The parents, patients, and nurses were blinded as to which
      group they were in. Postoperative pain scores were obtained using the FACES pain
      scale and recorded in a home diary. RESULTS: Seventy patients were recruited to
      the study, and 12 did not submit their diaries and were considered to drop out of
      the study. Demographic data were similar for both control and treatment groups.
      Median pain scores, medication use, days to normal diet, and office visits did
      not differ between the two groups. CONCLUSIONS: PRP applied once at the time of
      tonsillectomy does not improve postoperative pain or recovery in pediatric
      patients.

PMID- 18622316
TI  - The perichondrial cutaneous graft: a facial reconstructive option for the ages
      (ages 1 week to 94 years).
AB  - OBJECTIVES/HYPOTHESIS: The perichondrial cutaneous graft (PCCG) possesses unique
      characteristics that make them a propitious reconstructive option in facial
      plastic surgery. The PCCG is easily harvested from the conchal bowl. Notable
      characteristics are that it does not contract, unexcelled color match for
      resurfacing facial skin, and minimal donor site morbidity. This free graft
      frequently offers an expeditious solution to an otherwise more complicated
      reconstructive effort. STUDY DESIGN: Retrospective review of an academic
      otolaryngology and facial plastic surgery practice. METHODS: : Patients requiring
      head and neck reconstruction for cutaneous deficiencies were studied. The PCCG is
      harvested from the anterior conchal bowl. This is technically easy, and the
      perichondrium is tightly adherent to the dermis in this area. The donor site is
      closed by resecting a fenestra of conchal cartilage and rotating a posterior
      auricular interpolated island flap into the defect (the "flip-flop-flap"). The
      posterior auricular defect is easily closed in a linear fashion. The main outcome
      measures were cosmetic result, graft survival, donor site morbidity, and
      complications. RESULTS: There are 406 PCCGs in our series. Patients ranged in age
      from 7 days to 94 years. There were 170 grafts used for trauma and 236 used for
      reconstruction after skin cancer resection. Over the past 30 years in observing
      these grafts, there are no contractions noted in infants and children, growth
      with maturity is noteworthy. Cosmesis is excellent and in most cases superior to
      other skin grafting techniques. We have had four total failures and six partial
      losses of less than 30% for the PCCG. All complete failures were in patients with
      a smoking history. CONCLUSIONS: The PCCG is a very reliable flap for
      reconstruction of facial defects. It has been used in elderly and heavy smoking
      patients with minimal complications, attesting to its viability. The graft
      provides excellent cosmesis and it is an expeditious alternative to commonly used
      local flaps. It is especially useful in pediatric patients because the graft
      actually expands with growth. This is in contrast to the disadvantages of split
      thickness and full thickness skin grafts that predictably contract with maturity.
      Local flaps often lack adequate laxity for common implementation and make the
      PCCG a propitious choice in the pediatric patient.

PMID- 18622317
TI  - Is radical neck dissection a current option for neck disease?

PMID- 18622318
TI  - The skin-sternocleidomastoid muscle composite flap for neck dissection (the gator
      neck flap).

PMID- 18622319
TI  - Spontaneous nasal septal perforation with antiangiogenic bevacizumab therapy.
AB  - Otolaryngologists should be made aware of a newer cause of nasal septal
      perforations resulting from the more recent antiangiogenic therapy used to treat
      malignancies. This case describes a 52-year-old white woman who developed a
      spontaneous nasal septal perforation after given the antiangiogenic drug,
      bevacizumab, for metastatic ovarian cancer treatment. Bevacizumab is a recently
      developed monoclonal antibody against vascular endothelial growth factor receptor
      used to inhibit angiogenesis. The patient was ultimately treated with a nasal
      septal button with good symptom relief. This case documents the first report in
      the otolaryngology literature describing this new etiology for nasal septal
      perforations.

PMID- 18622320
TI  - Paradigms and progress in vocal fold restoration.
AB  - Science advances occur through orderly steps, puzzle-solving leaps, or
      divergences from the accepted disciplinary matrix that occasionally result in a
      revolutionary paradigm shift. Key advances must overcome bias, criticism, and
      rejection. Examples in biological science include use of embryonic stem cells,
      recognition of Helicobacter pylori in the etiology of ulcer disease, and the
      evolution of species. Our work in vocal fold restoration reflects these patterns.
      We progressed through phases of tissue replacement with fillers and biological
      implants, to current efforts at vocal fold regeneration through tissue
      engineering, and face challenges of a new "systems biology" paradigm embracing
      genomics and proteomics.

PMID- 18622322
TI  - Maximizing effectiveness of bisphosphonate therapy for osteoporosis.
AB  - While highly prevalent, osteoporosis is greatly underdiagnosed and undertreated
      in clinical practice. Even when appropriate treatments are prescribed, patient
      adherence to bisphosphonate therapy is low. As osteoporosis is a silent disease,
      and therapy is required for many months before benefit is realized, strategies to
      increase bone mineral density (BMD) and improve medication adherence are
      important aspects of every patient's care plan. Osteoporotic bone loss occurs
      without symptoms, and there are often no warning signs before a fracture occurs.
      Osteoporotic fractures are the most severe consequence of osteoporosis.
      Bisphosphonates are the most frequently prescribed treatment option for
      postmenopausal osteoporosis, as they effectively increase BMD, slow bone
      turnover, and reduce fracture rates. Strategies to improve adherence to
      osteoporosis therapy include reducing dosing frequency, changing the route of
      administration, educating the patient about optimum bisphosphonate
      administration, and sending patient reminders.

PMID- 18622323
TI  - Improper renal dosing in long-term care facilities.
AB  - OBJECTIVES: With advancing age, physiologic changes occur that affect drug
      metabolism. Possibly the most predictable function decline in geriatric
      population is renal function. METHODS: The prescribing habits of physicians and
      the attention given to patient renal function was investigated. Data was
      collected from two nursing facilities in southeastern Georgia. RESULTS: Based on
      two models of prescribing habits and using logistic regression estimates, we
      concluded that physicians do not follow recommendations for dose adjustment of
      renally excreted medications in these two facilities. CONCLUSION: We recommend
      that physicians consider evaluating current medications and establishing a base
      line for renal function and degree of decline.

PMID- 18622324
TI  - Cocaine abuse in pregnancy: an evolution from panacea to pandemonium.

PMID- 18622325
TI  - Placenta increta and cocaine abuse in a grand multipara leading to a second
      trimester rupture of an unscarred uterus: a case report.
AB  - A case of a uterine rupture in a grand multiparous patient with an unscarred
      uterus at 19 weeks' gestation secondary to placenta increta and cocaine abuse is
      presented. This was a diagnostically difficult case where abnormal implantation
      of the placenta, grand multiparity, and cocaine abuse were all contributors to
      the uterine rupture.

PMID- 18622326
TI  - Unadjusted medication dose in patients with chronic kidney disease.

PMID- 18622332
TI  - Endovascular grafting as a complement to open surgery treatment for axillary and
      subclavian vascular injuries.

PMID- 18622333
TI  - Thrombotic microangiopathy as a complication of medicinal leech therapy.
AB  - Medicinal leeches (hirudo medicinalis) are increasingly used as a useful
      therapeutic option in various medical and surgical settings. The potential
      complications associated with this therapy include infections with Aeromonas
      species, bleeding, anemia, and allergic reactions. We describe a patient who
      developed thrombotic microangiopathy and acute renal failure following leech
      therapy. It is proposed that the series of nonhuman proteins within leech saliva
      may be capable of injuring the endothelium.

PMID- 18622334
TI  - Primary malignant melanoma of the duodenum: aggressive management and long-term
      survival of an unusual oncologic entity.
AB  - Primary malignant melanoma originating in the small bowel is extremely rare. We
      report the case of a 55-year-old man who presented with a preoperative bleeding
      duodenal tumor. A standard pancreaticoduodenectomy was performed.
      Histopathological examination ascertained the diagnosis of a duodenal malignant
      melanoma with locoregional lymphatic spread. A thorough postoperative
      investigation did not reveal any primary melanotic lesions. Thus, the diagnosis
      of a primary melanoma originating from the duodenum was suggested. Fourteen
      months after surgery, the patient had no evidence of recurrence. Primary
      malignant melanoma of the duodenum is an existing, though unusual, oncologic
      entity. Aggressive surgery remains the treatment of choice offering both symptom
      palliation and long-term survival.

PMID- 18622335
TI  - Aortic dissection presenting as uniocular blindness.
AB  - A patient presented with uniocular blindness and headache, which was initially
      suspected to be subarachnoid hemorrhage. The patient had a seven-year history of
      diabetes mellitus, hypertension and hypothyroidism, as well as a two-year history
      of congestive cardiac failure with aortic regurgitation. Upon autopsy, the
      patient was diagnosed with aortic dissection. There are no other known reports of
      such a presentation. This case demonstrates that aortic dissection can present
      without any classical features, and hence it is important to consider the
      possibility of dissection in patients with long-standing hypertension and acute
      neurologic symptoms associated with pain.

PMID- 18622336
TI  - CT angiogram and endovascular stent graft for an axillary artery gunshot wound.
AB  - A patient with an axillary artery gunshot wound pseudoaneurysm was evaluated and
      managed with computed tomographic angiogram and endovascular stent graft.
      Vascular injuries resulting from penetrating trauma or interventional vascular
      procedures are relatively uncommon. Subclavian and axillary arterial injuries may
      be associated with substantial morbidity and mortality if not managed
      expeditiously. The inaccessibility of these arteries makes stent graft treatment
      particularly attractive. The stable patient with a pseudoaneurysm or an
      arteriovenous fistula seems to be the ideal candidate to treat in this way. As
      computed tomography (CT) technology has evolved, CT angiography has become an
      integral part of the initial assessment of proximal extremity vascular injuries.

PMID- 18622337
TI  - Fetal and neonatal Graves disease: a case report and review of the literature.
AB  - Fetal and neonatal thyrotoxicosis from maternal Graves disease is a very rare
      entity. Fetal symptoms result from the transplacental passage of thyroid
      stimulating immunoglobulins, which persist in the neonate resulting in neonatal
      symptoms. We present a case of fetal and neonatal thyrotoxicosis from maternal
      Graves disease. Fetal symptoms were controlled with maternal administration of
      antithyroid drugs leading to fetal thyroid inhibition. We present this case with
      a brief review of the literature.

PMID- 18622338
TI  - Isolated medial cuneiform fracture: a special forces soldier with a rare injury.
AB  - Isolated cuneiform fractures rarely occur, but must be considered in the
      differential diagnosis for midfoot injuries. Along with other nondisplaced,
      nondislocated midfoot injuries, these fractures are commonly missed or delayed in
      diagnosis. A review of the literature reveals only three other reported cases of
      isolated medial cuneiform fractures. Because of the difficulties with finding
      nondisplaced, nondislocated cuneiform fractures on plain film, further studies
      should be considered. Other medial cuneiform fractures found in the literature
      were nonisolated. This report describes a case of isolated medial cuneiform
      fracture in a 26-year-old Special Forces soldier that resulted in a significant
      delay of diagnosis.

PMID- 18622339
TI  - The effects of outpatient management on hospitalization for ambulatory care
      sensitive conditions associated with diabetes mellitus.
AB  - BACKGROUND: Ambulatory care sensitive conditions (ACSC) related to diabetes
      mellitus can potentially be prevented by good quality outpatient care. The
      purpose of this study was to evaluate which characteristics of ambulatory
      patients with diabetes were associated with ACSC hospitalizations. METHODS:
      Retrospective chart review of 65 adults with an ACSC diabetes-related
      hospitalization, and 130 controls with diabetes without ACSC hospitalizations.
      The primary outcome measure was the difference in hemoglobin A1c between groups.
      RESULTS: Patients with an ACSC hospitalization had poorer glucose control (mean
      A1c 9.24 versus 7.68, P < 0.001), but there was no difference in blood pressure
      or lipid control. CONCLUSIONS: Prevention of diabetes-related hospitalizations
      related more closely to glycemic control, rather than other important aspects of
      comprehensive care.

PMID- 18622341
TI  - The PC mouse as a learning tool for the development of eye-hand coordination for
      trainees in laparoscopic surgery.

PMID- 18622342
TI  - A man with sicca symptoms and bilateral parotid enlargement.

PMID- 18622343
TI  - Rapid rise in bed bug populations: the need to include them in the differential
      diagnosis of mysterious skin rashes.

PMID- 18622344
TI  - Physician signatures.

PMID- 18622345
TI  - Appropriateness of the use of serum ferritin or serum transferrin saturation as a
      diagnostic tool for the evaluation of anemia.

PMID- 18622346
TI  - The sociocultural dimensions of pain in the mid-South.

PMID- 18622347
TI  - Unusual metastatic soft tissue calcification in a hemodialysis patient.

PMID- 18622348
TI  - Poverty or big government: which is the real disease?

PMID- 18622349
TI  - The use of dopamine agonist in the treatment of restless legs syndrome: caution
      for practitioners and bipolar patients.

PMID- 18622350
TI  - Orthopaedic in-training examination performance: a nine-year review of a
      residency program database.
AB  - BACKGROUND: The Orthopaedic In-Training Examination (OITE) provides an objective
      way for both the residency program and the resident to monitor progress. METHODS:
      This longitudinal descriptive study tracks the OITE performance of 16 residents
      from one orthopaedic surgery residency program over nine years (1997-2005).
      Domain comparisons are made to national averages (N > 3000) by mean difference
      and split middle celeration line assessment trend analysis to evaluate program
      strengths and weaknesses. Further evaluation by postgraduate year (PGY) is made
      of domains that were deemed to be in need of moderate attention. RESULTS:
      Resident performance for the medically related issues, rehabilitation, and sports
      medicine domains were deemed acceptable. Resident performance on the orthopaedic
      science, orthopaedic diseases, hip and knee reconstruction, spine, and shoulder
      and elbow domains were deemed to be in need of minor attention. Musculoskeletal
      trauma, pediatric orthopaedics, foot and ankle, and hand domains were deemed to
      be in need of moderate attention. Further analysis of these domains by PGY
      revealed less positive slopes for the pediatric orthopaedics and musculoskeletal
      trauma domains, and a negative slope for the hand domain between PGY-3 and PGY-4,
      each indicative of lower domain-specific OITE scores than the national mean. A
      similar, less positive slope was identified between PGY-2 and PGY-3 for the foot
      and ankle domain. CONCLUSIONS: A longitudinal descriptive review of orthopaedic
      surgery resident OITE performance enables the departmental education committee to
      identify curricular content areas that require attention, select the most
      efficient modes of educational information delivery, facilitate learning through
      the application of innovative educational technologies, establish measurable
      educational program goals, and more prescriptively allocate personnel and
      equipment resources.

PMID- 18622351
TI  - Antihypertensive agents: are all of them equal?

PMID- 18622352
TI  - Characteristics of patients who present to the emergency department with molar
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to determine presenting signs/symptoms
      and risk factors in emergency department (ED) patients ultimately diagnosed with
      molar pregnancy. METHODS: A retrospective review of ED medical records using a
      standardized abstraction sheet was conducted over a 10-year period (1995-2005)
      from three EDs. RESULTS: Records were available on 44 patients (mean age 25.2
      years, 75% African-American) with a diagnosis of molar pregnancy who had been
      seen in the ED. Almost half presented with abdominal pain, nausea/vomiting,
      and/or vaginal bleeding. Forty-three percent had a history of sexually
      transmitted disease; 41% had a history of abdominal or gynecological surgery; and
      three patients had a documented prior molar pregnancy. Of 22 ultrasounds
      performed, 68% were noted to have a molar pregnancy. Only five patients had molar
      pregnancy listed in the differential diagnosis at their initial visit.
      CONCLUSION: Patients who presented with molar pregnancy tended to be young,
      multiparous, and African-American. The most common presenting complaint was
      vaginal bleeding, and the ultrasound was not diagnostic of molar pregnancy in
      almost one-third of the cases.

PMID- 18622353
TI  - The pleiotropic effects of antihypertensive agents: do they account for
      additional cardiovascular benefit beyond BP reduction?
AB  - Hypertension commonly clusters with other cardiovascular risk factors, giving
      rise to the concept that hypertension is a multifaceted disease that potentially
      shares common pathogenic pathways with other risk factors. The renin-angiotensin
      aldosterone system has a central role in the shared mechanisms of hypertension
      and cardiovascular disease, primarily through angiotensin II. Increased levels of
      angiotensin II disrupt the balance of vasoactive substances and growth factors
      that regulate endothelial structure and function, and inhibition of the renin
      angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor or
      angiotensin II type 1 receptor blocker helps restore this equilibrium. Some
      pathogenic mechanisms may also be favorably affected by calcium channel blockade.
      While the relative contribution of pleiotropic effects to clinical benefit is
      difficult to quantify, based on recent data it is reasonable to consider using
      newer antihypertensive agents in selected high-risk patients to realize the
      benefits that may derive from interfering with pathogenic mechanisms of disease.

PMID- 18622354
TI  - Stress test: a primer for primary care physicians.
AB  - Although stress testing is generally a safe procedure, complications may occur.
      Types of stress tests include electrocardiographic exercise stress test,
      myocardial imaging exercise stress test, and myocardial imaging pharmacological
      stress tests. Nuclear imaging stress test is a preferable modality in women.
      Exercise-based stress tests provide evaluations of functional capacity, as well
      as their blood pressure and heart rate recovery rate, which offer additional
      diagnostic and prognostic information. Exercise-based stress tests should be
      considered before using a pharmacological-based test. Different exercise
      protocols are available, dependent on patients' clinical status. Patients
      incapable of achieving 5 metabolic equivalent units (METs) of exercise should
      have a pharmacological stress test. Different pharmacological agents are
      available for stress tests, and the agents' choice depends on the patients'
      characteristics and their medications. Some markers may indicate a highly
      positive stress test, which warrants immediate attention. Indications,
      contraindications, and precautions for stress test modalities are discussed in
      this article.

PMID- 18622356
TI  - Sterility of C-arm fluoroscopy during spinal surgery.
AB  - STUDY DESIGN: Prospective study evaluating the sterility of 25 C-arm drapes after
      their use during spine surgery. OBJECTIVE: To use swab samples to evaluate the
      sterility of draped C-arms at the end of spine surgical cases and assess the
      integrity of the sterile technique. SUMMARY OF BACKGROUND DATA: Intraoperative
      fluoroscopy is used routinely in the operating room for a variety of spinal
      applications. Although the C-arm may help the surgeon assess spinal alignment and
      facilitate the placement of instrumentation, there are concerns that the C-arm
      may represent a potential source of contamination and increase the risk of
      developing a postoperative infection. METHODS.: This study included 25 surgical
      cases requiring a standard fluoroscopic C-arm that were performed by 2 spine
      surgeons. Sterile culture swabs were used to obtain samples from 5 defined
      locations on the C-arm drape after its use during the operation. The undraped
      technician's console was sampled in each case as a positive control and an
      additional 25 C-arm drapes were swabbed immediately after they were applied to
      the C-arm unit in order to obtain negative controls. Swab samples were assessed
      for bacterial growth on 5% sheep blood Columbia agar plates using a
      semiquantitative technique. RESULTS: Contamination was noted on only 1 of 25
      negative control drapes at a single location (4%). One hundred percent and 96% of
      the positive control swabs that were obtained from the negative controls and
      postoperative drapes exhibited growth, respectively. Although at least some
      degree of contamination was observed at all locations of the C-arm drape after
      surgery, the upper 2 sample sites demonstrated the greatest degree of
      contamination; the incidences of postoperative contamination were significantly
      greater for the top (56%, P < 0.000001) and upper front of the receiver (28%, P =
      0.010) compared to the negative controls. In contrast, the lower front, receiver
      plate, and midportion of the C-arm were associated with lower rates of
      contamination (12%-20%). CONCLUSION: The upper portions of the C-arm clearly
      exhibited the greatest rates of contamination during spinal operations. This
      contamination most likely occurs when the undraped portions of the C-arm are
      rotated to acquire lateral images. As a result, we no longer consider the top
      portion of the C-arm drape to be sterile in these situations and we believe that
      avoiding contact with these areas may decrease the risks of intraoperative
      contamination and possibly postoperative infection as well.

PMID- 18622355
TI  - Biologic response of human intervertebral disc cells to gene therapy cocktail.
AB  - STUDY DESIGN: In vitro experiment using human intervertebral disc (IVD) cells and
      adenovirus-therapeutic gene constructs. OBJECTIVE: To examine the biologic effect
      of "cocktail" therapeutic gene transfer to human IVD cells in three-dimensional
      cultures. SUMMARY OF BACKGROUND DATA: Gene therapy is regarded as a potential
      option for the treatment of degenerative disc disease. Although various anabolic
      genes have previously been introduced for this purpose, cocktail gene transfer of
      anabolic genes to IVD cells has never been attempted. METHODS: Human IVDs were
      harvested during surgical disc procedures and cultured. We prepared recombinant
      adenovirus constructs bearing the TGF-beta1 gene (Ad/TGF-beta1), the IGF-1 gene
      (Ad/IGF-1), and the BMP-2 gene (Ad/BMP-2). Transgene expression was detected by
      luciferase assays, enzyme linked immunosorbent assays, and Western blot analysis.
      Newly synthesized proteoglycan was measured by S-sulfate incorporation on
      Sephadex G-25 M in PD 10 columns. Human IVD cells were transduced by single,
      double, and triple combination of Ad/TGF-beta1, Ad/IGF-1, Ad/BMP-2 with an MOI of
      75, then cultured three-dimensionally in alginate beads. RESULTS: Transgene
      expression was detected at 18 hours after viral transduction. IVD cultures with
      Ad/TGF-beta1, Ad/IGF-1, Ad/BMP-2 (MOI of 75) showed 2.9, 1.8, and 1.9 fold
      increases, respectively, in proteoglycan synthesis compared to control. Human IVD
      cultures with double gene combination (MOI of 75) showed 3.2 to 3.9 fold
      increases of proteoglycan synthesis. Lastly, Human IVD cultures with triple gene
      combination (TGF-beta1+IGF-1+BMP-2 genes with an MOI of 75) transfer demonstrated
      4.7 fold increase in proteoglycan synthesis compared control. CONCLUSION:
      Combination or "cocktail" gene therapy offers a promising mechanism for
      maximizing matrixsynthesis with low dose of adenoviral mixtures, circumventing
      systemic, local toxic effect, and immune response.

PMID- 18622357
TI  - Costs and state-specific rates of thoracic and lumbar vertebroplasty, 2001-2005.
AB  - STUDY DESIGN: Sequential cross-sectional analysis. OBJECTIVE: To document
      vertebroplasty rates and costs. SUMMARY OF BACKGROUND DATA: Little is known about
      interstate variation in rates or about nation-wide costs associated with the
      growing use of percutaneous vertebroplasty. METHODS: Using specific CPT-4 billing
      codes, we reviewed aggregate Medicare Part B fee-for-service claims data (cross
      stratified by physician specialty and treatment setting) on thoracolumbar
      vertebroplasties performed from 2001-2005. Vertebroplasty rates for individual
      states were expressed per 100,000 Part B fee-for-service enrollees. Nation-wide
      facility and physician charges (combining expected contributions from all
      sources) allowed by Medicare for vertebroplasties and associated imaging guidance
      procedures were applied to observed vertebroplasty volumes. These charges
      (reflecting direct medical costs from an all-payer perspective) were expressed in
      2005 dollars using the Producer Price Index. RESULTS: Vertebroplasty rates for
      individual states rose but varied considerably, ranging from 0.0 to 515.6/100,000
      Medicare Part B fee-for-service enrollees in 2001 (median state rate = 35.4), and
      from 9.8 to 849.5 in 2005 (median state rate = 75.0). On average, 1.3 vertebral
      levels were treated per procedure, varying by treatment site and physician
      specialty. Fluoroscopic rather than computed tomography guidance was used in
      98.7% of cases. Total nation-wide inflation-adjusted charges rose from $76.0
      million for 14,142 cases performed in 2001 to $152.3 million for 29,090 cases in
      2005. While vertebroplasty was predominantly an outpatient procedure, inpatient
      cases generated most of the charges. Increasing volumes and costs were associated
      with cases performed in ambulatory surgery centers and physicians' offices.
      CONCLUSION: Nation-wide vertebroplasty volumes and inflation-adjusted charges
      doubled from 2001 to 2005 in this Medicare population. Procedure rates varied
      considerablyby state. Almost all cases involved fluoroscopic guidance; procedures
      treating multiple vertebral levels were not uncommon. Procedures performed in
      free-standing facilities are of growing importance. Given the issues surrounding
      appropriate vertebroplasty use, future practice patterns and outcomes should be
      closely tracked.

PMID- 18622358
TI  - Rare metabolic syndromes, a vascular hypotheses of Alzheimer's disease, and drug
      developments for attention and trauma.

PMID- 18622359
TI  - Back to Briquet and Charcot.

PMID- 18622360
TI  - Depression, anhedonia, and psychomotor symptoms: the role of dopaminergic
      neurocircuitry.
AB  - The heterogeneity of major depression suggests that multiple neurocircuits and
      neurochemicals are involved in its pathogenesis. Anhedonia and psychomotor
      symptoms are, however, particularly characteristic features of major depression
      and may provide insights into its underlying psychobiology. Importantly, these
      symptoms appear to be mediated by dopaminergic mesolimbic and mesostriatal
      projections, the function of which is, in turn, influenced by key gene variants
      and environment stressors. Indeed, there is growing evidence of the way in which
      the dopaminergic system is associated with cognitive-affective disturbances in
      depression, and provides a useful target for therapeutic interventions. At the
      same time, a range of other systems are likely to contribute to the psychobiology
      of this condition.

PMID- 18622361
TI  - Selective serotonin reuptake inhibitors and initial oral contraceptives for the
      treatment of PMDD: effective but not enough.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are almost
      unanimously considered to be very efficacious and the first line of pharmacologic
      treatment for premenstrual dysphoric disorder (PMDD) and premenstrual syndrome
      (PMS). There is a need to examine if this is actually the case. More recently,
      combined oral contraceptives (COCs) have been pursued due to their ovulation
      suppression effects. Their effects on PMS/PMDD should be further examined as
      well. METHODS: For this review of the literature from 1990 to the present,
      MEDLINE, PsychLit, and Cochrane controlled trials register were searched.
      Randomized, double-blind, placebo-controlled clinical trials of SSRIs and COCs
      (N>20) that report the rate of responders and not just percent improvement in
      severity of symptoms were selected for study. The data extraction were the
      percentage or number of responders as reported by the original authors. RESULTS:
      In many studies, only mean improvement in severity was reported. In all studies,
      the main inclusion criterion was meeting criteria for PMDD; this has not,
      however, been an outcome measure. However, only 16 reports that provided actual
      rate of responders could be included. The percentage of non-responders (100%
      minus active medication) to SSRIs and COCs was found to be higher than the
      reported percentage of women who responded to active medication (response rate to
      an SSRI or COC minus the response rate to placebo). CONCLUSION: In the majority
      of larger-scale studies, once the placebo effect is accounted for, the percentage
      of women who respond to SSRIs or COCs is actually less than the percentage of
      women who do not respond at all. SSRIs provide an important step forward in the
      treatment of PMDD and PMS. COCs provide a different option, still, approximately
      40% of women with PMDD do not respond to SSRIs. Treatment with a currently
      approved COC does not substantially improve the percentage of responders.
      Therefore, additional alternative targeted treatment modalities need to be
      developed.

PMID- 18622362
TI  - A psychodynamic understanding of conversion nonepileptic seizures in a young
      woman with acquired blindness.

PMID- 18622363
TI  - The role of the glutamatergic system in posttraumatic stress disorder.
AB  - Antiglutamatergic agents, such as lamotrigine, have been used successfully for
      the treatment of posttraumatic stress disorder (PTSD). They could be potentially
      acting through the stabilization of the corticotropin-releasing factor (CRF)
      systems. Glutamate mediates CRF release in various brain regions involved in the
      pathophysiology of PTSD, antiglutamatergic agents could stabilize the CRF system
      and, thereby, improve the symptom complex of PTSD (reexperiencing, hyperarousal,
      and avoidance). The role of glutamate and CRF in PTSD and other anxiety disorders
      are still being elucidated. However, it is clear that the glutamatergic systems
      play a role in the pathophysiology of PTSD.

PMID- 18622365
TI  - Metabolic syndrome and Alzheimer's disease: a link to a vascular hypothesis?
AB  - Current evidence from epidemiological, neuroimaging, pathological,
      pharmacotherapeutic, and clinical studies indicate an association of Alzheimer's
      disease with risk factors of vascular atherosclerotic disease either in isolation
      or in aggregate. "Metabolic syndrome" (MetS) is the name for a clustering of risk
      factors for cardiovascular disease and type 2 diabetes that are of metabolic
      origin. These include central obesity, elevated plasma glucose, high blood
      pressure, atherogenic dyslipidemia, a prothrombotic state, and a proinflammatory
      state. In this article, we provide an overview of the relevant literature with
      regard to the relationship of Alzheimer's disease with MetS. Accumulating
      evidence suggests a "vascular hypothesis" to be related to the pathology of
      Alzheimer's disease. In the light of this evidence, clinician may consider
      lifestyle interventions toward an early and effective cardiovascular risk-factor
      management to reduce the cardiometabolic and the cognitive decline risk, while
      further research of other preventive strategies may be warranted.

PMID- 18622364
TI  - Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde
      dehydrogenase deficiency patients.
AB  - INTRODUCTION: Succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma
      hydroxybutyric aciduria) is a rare neurometabolic disorder of gamma-aminobutyric
      acid degradation. While neurological manifestations, such as developmental delay,
      are typical during infancy, limited data are available on adolescent and adult
      symptomatology. METHODS: We overview the phenotype of 33 adolescents and adults
      (10.1-39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency.
      For this purpose, we applied a database with systematic questionnaire-based
      follow-up data. RESULTS: Sixty-six percent of patients (n=21) presented by 6
      months of age, 14% from 6-12 months of age, 5% from 1-2 years of age, and 14%
      from 2-4 years of age, mean age at first symptoms was 11+/-12 months. However,
      mean age at diagnosis was 6.6+/-6.4 years of age. Presenting symptoms encompassed
      motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia.
      Eighty-two percent demonstrated behavioral problems, such as attention deficit,
      hyperactivity, anxiety, or aggression, and 33% had >or=3 behavior problems.
      Electroencephalograms showed background slowing or epileptiform discharges in 40%
      of patients. Treatment approaches are then summarized. CONCLUSION: The variable
      phenotype in SSADH deficiency suggests the likelihood that this disease may be
      under-diagnosed. Families of patients with SSADH deficiency should be counseled
      and supported regarding the anticipated persistence of various neuropsychiatric
      symptoms into adulthood.

PMID- 18622366
TI  - Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged
      children with attention-deficit/hyperactivity disorder.
AB  - INTRODUCTION: Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is
      indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6-12
      years of age and in adults. In short-term studies, once-daily LDX provided
      efficacy throughout the day. This study presented here was conducted to assess
      the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year
      olds with ADHD. METHODS: This open-label, multicenter, single-arm study enrolled
      children with Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition-Text Revision criteria for ADHD. Following 1-week screening and washout
      periods, subjects were titrated to LDX 30, 50, or 70 mg/day over 4 weeks and
      placed on maintenance treatment for 11 months. The ADHD Rating Scale and Clinical
      Global Impression-Improvement scale measured effectiveness. RESULTS: Of 272
      subjects receiving LDX, 147 completed the study. Most adverse events were mild to
      moderate and occurred during the first 4 weeks. There were no clinically
      meaningful changes in blood pressure or electrocardiographic parameters. From
      baseline to endpoint, mean ADHD Rating Scale scores improved by 27.2 points
      (P<.0001). Improvements occurred during each of the first 4 weeks, and were
      maintained throughout. Based on Clinical Global Impression-Improvement scale
      scores, >80% of subjects at endpoint and >95% of completers at 12 months were
      rated "improved." CONCLUSION: Long-term 30, 50, and 70 mg/day LDX was generally
      well tolerated and effective in children with ADHD.

PMID- 18622367
TI  - Everyday problems in treating depression: focus on SNRIs. Introduction.

PMID- 18622368
TI  - Recognizing and effectively treating depression.
AB  - In 2004, more people died in Europe from suicide than from road accidents. The
      lifetime prevalence of major depression is 20% for women and 10% for men.
      Depression is a leading cause of disability and decreased quality of life. In
      spite of this, numerous studies have shown that only approximately 50% of
      depressed patients are recognized as such in primary care. In a recent
      international survey of everyday management of depression we observed that only
      approximately 15% of patients became symptom-free following treatment. In spite
      of this low level of remission primary care physicians and psychiatrist only
      rarely increased the dose of antidepressant or switched to another medication as
      unanimously recommended by different guidelines. Numerous studies have
      demonstrated the importance of maintaining treatment for >6 months after
      remission is obtained in order to prevent relapse and recurrence. However, a
      recent study reported that only 19% of a cohort of patients in primary care
      continued treatment for 6 months as recommended. Antidepressants can be very
      effective but only when used correctly at adequate doses and for a sufficient
      duration. Although new improved antidepressants are obviously desirable, a
      greater recognition of depression and its treatment by the correct use of
      currently available antidepressant drugs could greatly improve the management of
      this major public health problem.

PMID- 18622369
TI  - Initial effectiveness, partial remission, and full remission in depression: focus
      on long-term treatment with SNRIs.
AB  - Full remission, defined as the absence of all significant symptoms of depression
      over at least 6 months, is the ultimate goal of antidepressant therapy. Remission
      takes time and studies have shown that remission rates continue to rise for at
      least 3 months after initial improvement. Depression is a recurrent condition
      with a cumulative probability of recurrence of 40% over 2 years and 70% over 5
      years after the first depressive episode. In addition the risk of recurrence
      increases with each new depressive episode. Continuing antidepressant treatment
      beyond the acute response significantly decreases the risk of recurrence. A
      double-blind study with the serotonin norepinephrine reuptake inhibitor
      milnacipran, for example, has shown that patients in remission following
      treatment with milnacipran who continued the active treatment for a further 12
      months had significantly less relapse (P<.05) than those switched to placebo. In
      spite of the importance of maintaining antidepressant therapy, many patients do
      not continue treatment. Among the principal reasons for this are side effects and
      worries of psychological or physical dependence. To reduce the risk of relapse,
      treatment with effective, well-tolerated antidepressants with few withdrawal
      effects should be pursued for at least 6 months and possibly longer in patients
      already experiencing relapse.

PMID- 18622370
TI  - Treating depression with SNRIs: who will benefit most?
AB  - There is evidence that the serotonin norepinephrine reuptake inhibitors (SNRIs)
      venlafaxine, milnacipran, and duloxetine, have probable superior antidepressant
      activity to most selective serotonin reuptake inhibitors (SSRIs), especially in
      more severe depression. Some patients, however, respond better than others to
      SNRIs. Several factors influencing response to milnacipran have been recently
      studied. The presence of certain polymorphisms related to noradrenergic
      neurotransmission has been shown to be related to different degrees or rapidity
      of response to milnacipran. In addition, patients with low pretreatment levels of
      plasma 3-methoxy-4-hydroxyphenylglycol have a better response to milnacipran.
      These recent genomic and neurochemical data confirm that milnacipran, in contrast
      to SSRIs and venlafaxine, has an impact on the noradrenergic system. Differences
      in metabolism determined by genetic variables in cytochrome P450 (CYP) 2D6
      activity are a major determinant of venlafaxine levels to such an extent that
      genetically determined decreases in CYP 2D6 activity have been associated
      increased adverse effects. Milnacipran, which is not metabolized by the enzymes
      of the CYP system is not influenced by polymorphism of these enzymes. These
      preliminary data suggest that a patient's biochemical and pharmacogenetic
      characteristics may be useful in the future to help clinicians chose the most
      effective antidepressant medication.

PMID- 18622371
TI  - Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors.
AB  - Comorbid chronic pain is common in depressed patients. It is predictive of a poor
      prognosis for depression and is a major risk factor for suicidal behavior.
      Depression and chronic pain may result from a common neurobiological dysfunction
      of monoamine cell bodies in the basal ganglia. Amitriptyline, which inhibits both
      serotonin and norepinephrine reuptake, is a preferred treatment of chronic pain
      although it is not officially indicated for this condition. Chronic pain can be
      modeled in animals where amitriptyline has been shown to be highly effective.
      Similar effects are obtained with the serotonin norepinephrine reuptake
      inhibitors milnacipran, duloxetine, and venlafaxine, whereas selective serotonin
      reuptake inhibitors (SSRIs) are only weakly active. Both animal and clinical
      studies of chronic pain show that dual-acting reuptake inhibitors are more active
      than selective norepinephrine reuptake inhibitors, which are, in turn, more
      active than SSRIs. A meta-analysis of placebo-controlled studies confirmed that
      dual-action antidepressants, but not SSRIs, were effective in reducing chronic
      lower-back pain. Milnacipran, duloxetine, and venlafaxine, have all been reported
      to be effective in a number of chronic pain conditions, including the treatment
      of fibromyalgia where their analgesic effects are independent of comorbid
      depression.

PMID- 18622372
TI  - Tolerability of serotonin norepinephrine reuptake inhibitor antidepressants.
AB  - All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the
      reuptake of both serotonin and norepinephrine but they do so with differing
      affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for
      norepinephrine while duloxetine has a 10-fold selectivity for serotonin.
      Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of
      the two neurotransmitters. The most frequent adverse event with SNRIs is nausea.
      Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as
      dry mouth, sweating, and constipation, are found more frequently with SNRIs than
      with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is
      associated with dose-dependent cardiovascular phenomena (principally increased
      blood pressure), an effect which is less frequent with duloxetine and rare with
      milnacipran. Serious and potentially fatal hepatotoxity has been reported with
      duloxetine. This problem appears to be unique to duloxetine and not a
      characteristic of the SNRI class. There are differences in overdose toxicity
      between venlafaxine and the other SNRIs, possibly related to its increased
      cardiotoxicity.

PMID- 18622373
TI  - [Pilot study on M2-PK-- a new non-invasive parameter for early diagnosis of
      colorectal carcinoma].
AB  - To determine the level of tumor marker pyruvate kinase dimer (M2-PK) in the feces
      of patients with colorectal cancer and benign polyps, as well as in individuals
      with chronic inflammatory bowel diseases. Fecal M2-PK determination could be
      outlined as a highly reliable non-invasive approach to the diagnosis of
      colorectal carcinoma. The establishing of elevated values in patients with
      chronic inflammatory bowel diseases decreases the specificity of M2-PK as a tumor
      marker. However, this does not compromise its essential clinical significance,
      because the precise diagnosis in both diseases imposes an obligatory performance
      of colonoscopy.

PMID- 18622374
TI  - [Surgical pain control and quality of life improvement in patients with
      nonoperable supramesocolic neoplasm by using thoracoscopic splanchicectomy
      (TSS)].
AB  - In patients, suffering from malignancies, pain is still predominant symptom. The
      control of carcinogenic pain has to be led with all known sources and methods:
      medications, surgical methods and interventional methods. Since august 2004 in a
      period of 34 months there have been examined 50 patients with abdominal viscera
      malignancies, located in between transversal colon and diaphragm, i.e having the
      same sympathetic innervations and suffering from pain, located in the upper
      abdomen, due to the illness. There have been examined the influence of pain level
      and quality of life improvement after TSS of the investigated group. TSS is easy
      to perform surgical method with good possibilities in visceral pain control in
      supramesocolic neoplasmas, with insignificant intra and postoperative
      complications. TSS improves the quality of life of patients with nonoperable
      supramesocolic neoplasms.

PMID- 18622375
TI  - [Laparoscopic pelvic lymph node dissection-- method for prostate cancer staging].
AB  - INTRODUCTION: Laparoscopic pelvic lymph node dissection is recently widely used
      method for surgical staging for prostate cancer. The first case in urology has
      been reported in 1991 from Schuessler et al. AIM: The aim of this study was to
      evaluate the surgical results from our first 20 cases of laparoscopic pelvic
      lymph node dissection. We analyze the operative time, blood loss, intraoperative
      et postoperative complications, number of lymph nodes, pain, hospital stay. To
      compare results of the first 10 and second 10 operations. MATERIALS AND METHODS:
      Between April 2003 and December 2006 in our Clinic have been operated 20 patients
      with adenocarcinoma of prostate. Median age was 64.4 years. Median prostate
      specific antigen was 53.7 ng/ml. Clinical methods - digital rectal examination of
      prostate, transrectal ultrasound punction biopsy of prostate, level of hemoglobin
      in blood to evaluate the blood loss. Operative method - transperitoneal
      laparoscopic pelvic bilateral pelvic lymph node dissection. RESULTS: Mean
      operative team for the first 10 cases was 178 minutes, and for the second 10
      cases - 68.5 minutes. Hemotransfusion in first case only. No medication for pain
      in 6 cases, injectable medication in 7 cases and as tablet form in 3 patients.
      Median number of lymph nodes - 8 /0-15/. Median hospital stay 5,7 days/11-3/. No
      major complications, no conversion. One case of symptomatic lymphocele.
      CONCLUSION: Laparoscopic pelvic lymph node dissection is a endoscopic method with
      short operative time, minimal blood loss, low level of pain, short hospital stay.
      The operative results are getting better after the first ten operations. This
      method is a useful for minimally invasive staging of prostate cancer.

PMID- 18622376
TI  - [Analysis of the results of femoro-popliteal arterial bypasses depending on the
      clinical stage of disease].
AB  - The strategy of treating infra inguinal arterial lesions according to the
      clinical Fontaine stage is very difficult and complicated. Critical limb ischemia
      is considered a strong indication for revascularization without delay. It is
      still not clear what operative treatment should be chosen for patients in
      Fontaine stage II. Early femoro-popliteal bypass reconstruction is a new
      practical doctrine and the wise alternative before the onset of severe and
      irreversible changes in the peripheral arterial vessels and the microcirculation.
      This conception takes a very important part in the evaluation of the long-term
      perspective of patients.

PMID- 18622377
TI  - [Posterior screw fixation for craniocervical junction instability].
AB  - INTRODUCTION: The craniocervical junction (C0-C2) is anatomically and
      biomechanically the most complex spinal region. It is frequently engaged by
      different pathologies of tumoral, traumatic or inflammatory origin, leading to
      spinal instability. We are presenting our experience with the posterior screw
      fixation for the treatment of the craniocervical junction instabilities. MATERIAL
      AND METHODS: Six posterior screw fixation of the craniocervical junction with the
      DePuy cervical fixation system - Summit were made for a period of 9 months. In 5
      cases the instability was caused by a traumatic injury and in 1 - by a
      malignancy. A C1- C2 fixation was made in 1 case, C2 - C3 in 2 cases, C0-C2-C3-C4
      in 2 cases and N0 - N3 - N4 - N5 in 1 case. RESULTS: No complications related to
      the surgical technique applied were observed. No dural, neural or vascular
      damages were provoked. In all cases the postoperative course was uneventful. The
      early clinical and radiologic follow-up data were satisfactory. CONCLUSION: Our
      data suggest that the posterior screw fixation is a reliable and efficient option
      for surgical treatment of craniocervical instability.

PMID- 18622378
TI  - [Oxidative stress: unsolved problem in the complex therapy in critically ill
      patients].
AB  - BACKGROUND: Recent reports emphasize the important role of oxidative stress in
      the genesis of many syndromes and diseases. The ICU patients have prerequisites
      for activation of oxidative stress process: activation of the neutrophils,
      macrophages, and other cells which are capable of producing reactive oxygen
      species (ROS). The traditional opinion was that lipids are the primary target of
      the ROS but new data show also protein damage. The interaction between ROS and
      lipids is an indicator for oxidative stress. OBJECTIVE: Complex investigation of
      the parameters of oxidative stress in critically ill patients undergoing
      abdominal surgery. METHODS: Eight patients undergoing surgery for diffuse
      peritonitis or acute pancreatitis were examined. The intensity of the lipid
      peroxidation processes was defined by the TBA-RS plasma levels. The status of the
      plasma antioxidant system was assessed by desoxyribose method. Patients with
      malignant diseases were not included. RESULTS: Our results confirm the growth of
      oxidative stress in study patients. We observed consistent increase in MDA levels
      toward 3rd-5th day of postoperative period. CONCLUSIONS: Oxidative stress
      processes have an important role in the course and outcome of surgical ICU
      patients. Multiple organ failure in these patients correlates well with the
      oxidative damage of body's protein structures. It is advisable to monitor the
      parameters of oxidative stress and protein damage in the course of critical
      illnesses.

PMID- 18622379
TI  - [Diagnostic and treatment of carotid bodies tumors].
AB  - Carotid body tumor is rare neoplasm (about 0,5 per cent of all tumors).[28]. The
      tumor arise from paraganglionic cells of carotid body, which develops from both
      mesodermal elements of the third branchial arch and neural elements originating
      from the neural crest ectoderm.[25]. Mathews warned: "this rare tumor presents
      unusual difficulties to the surgeon, and should one encounter it without having
      suspected the diagnosis, the experience will not soon be forgotten".[19]. The aim
      of this retrospective study is to investigate the frequency, number of spreading
      and results from the treatment in patients with carotid bodies tumors. MATERIALS
      AND METHODS: Eleven patients (2,58%) with carotid bodies tumors were diagnosed
      and operated under upon from January 1990 to June 2007 at the "Department of
      Vascular surgery and Angiology" of "St. Ekaterina" University hospital - Sofia,
      from commonly 427 surgical intervention in the area of carotid triangle for the
      same period. The clinical picture, operating time and blood loss during the
      surgery were examined. Careful subadventitial dissection was used like a method,
      which have to reduce the number of postoperative complications and blood loss.
      RESULTS: All 11 patients were operated upon with endotrachial anesthesia and in
      two of them there was intracranial nerves injure, reconstruction of carotid
      artery has established in two of the patients. In the early postoperative period
      there was disphagia in three of the patients, four were with partial damage of n.
      hypoglossus, two- with damage of the face branch of n. facialis and six with
      parasthesia at the operated side. CONCLUSION: CT angiography of carotid
      bifurcation has established as basic method in the diagnostic. Total extirpation
      of the tumor remains the basic method of treatment from high quality specialists
      in carotid surgery. Careful subadvetitial dissection and accuracy excision allow
      the whole separation of the tumor from the carotid bifurcation without traumatic
      lesion. [28].

PMID- 18622380
TI  - [Prognostic factors for survival in primary liver cancer].
AB  - BACKGROUND: The aim of this study was to identify the prognostic factors of
      survival after curative resection of primary liver cancer (PLC). STUDY DESIGN:
      Thirty four patients underwent resection PLC between January 1991 and December
      2000. Univariate and multivariable analysis were used to retrospectively identify
      factors associated with overall survival when resection was curative for primary
      tumor. RESULTS: Overall 1, 2, 3 and 5 - year survival rates were 76.0%, 57.5%,
      35.2% and 6.0% respectively. Recurrence after one year was 35%. Eleven predictive
      factors - clinical, laboratory, pathological and surgical were analyzed.
      Independent prognostic factors for overall survival were vascular invasion (p =
      0.006) and stage (p = 0.023). CONCLUSIONS: Hepatic resection is an effective
      treatment for PLC, even in advanced cases. The overall survival were low, because
      of late diagnosis and recurrence of the tumors.

PMID- 18622381
TI  - [Anal incontinence--new methods of surgical treatment using artificial bowel
      sphincter and sacral nerve stimulation].
AB  - Anal incontinence remains a largely hidden problem, with many patients which are
      long-term health and mobility problems. Anal incontinence is a symptom or sign
      rather than a disease, and that there are often multiple contributory factors.
      Anal incontinence affects both sexes and all age groups. Approximately 2% of the
      adult population have it on a frequent basis. Treatments include pelvic muscles
      training, drugs, surgery. Artificial bowel sphincters and sacral nerve
      stimulation (or neuromodulation) is a relatively new operative techniques for
      treating anal incontinence and are used in patients with an intact or repaired
      sphincter complex.

PMID- 18622382
TI  - [Surgical tactics in gunshot injuries of the rectum].
AB  - Gunshot rectal injuries, although uncommon, are a source of significant morbidity
      and mortality. These injuries are associated with a significant potential for
      life-threatening septic complications if they are not recognized and treated
      promptly. The gold standard has been intestinal diversion, primary rectal repair,
      distal rectal washout and presacral drainage. The management of these injuries
      has evolved, and controversy now exists as to the need for each of these
      maneuvers. An approach based on mechanism and degree of tissue destruction,
      location of injury, and associated organ involvement is now advocated.

PMID- 18622383
TI  - [Endovascular procedures in case of cancers engaging the vessels of the small
      pelvis].
AB  - Cervix cancer is quite common nowadays. Its progress is followed by painful
      symptomatology, urosepsis, lymphedem, flebothrombosis and ischemia of the lower
      limbs. The surgical treatment and the following chemotherapy and radiotherapy
      causes proliferation of the fibroid tissue, which embraces and presses the
      vessels of the small pelvis. We are to depict two clinical cases in which the
      choice of the percutaneous transluminal angioplasty and the implementation of a
      covered stent - graft is preferable to the open surgery. During the predilatation
      with a balloon catheter, our first patient suffered of a vessel rupture,
      visualized on the intraoperative angiogram. The rupture of vessel during
      angioplasty usually demands open surgical correction, but endovascular procedure
      can provide a fast, efficient, and less aggressive method. Covered stent-grafts
      are applicable for both treatment and stabilization of vessel lesions.

PMID- 18622384
TI  - Clinicopathological features and global genomic copy number alterations of
      pilomyxoid astrocytoma in the hypothalamus/optic pathway: comparative analysis
      with pilocytic astrocytoma using array-based comparative genomic hybridization.
AB  - Pilomyxoid astrocytoma is a recently identified variant of pilocytic astrocytoma.
      We studied 11 circumscribed astrocytomas with focal (n=5) or diffuse (n=6)
      pilomyxoid features and compared them with 17 pilocytic astrocytomas from the
      hypothalamic/chiasmatic region in children. In one patient, a tumor that recurred
      after initial surgery had changed from pure-form pilomyxoid astrocytoma to the
      mixed form. The presence of a pilomyxoid area was associated with shorter
      survival. Next, we compared the comprehensive genome copy number changes in the
      pilomyxoid astrocytoma (n=4) with those in pilocytic astrocytoma (n=6) cases by
      array-based comparative genomic hybridization. The number of lost clones was
      larger in pilomyxoid astrocytoma than in pilocytic astrocytoma. Clones located in
      chromosome 8q24.3 were frequently gained in pilocytic astrocytoma (four of six)
      and in pilomyxoid astrocytoma (one of four). Clones located in 9p24.3 and 15q26.3
      were lost in all of the pilomyxoid astrocytomas and in five of the pilocytic
      astrocytomas. Those in 8p23.3 showed a copy number loss in three of the
      pilomyxoid astrocytomas and four of the pilocytic astrocytomas. The frequency of
      copy number changes was significantly different between pilomyxoid astrocytoma
      and pilocytic astrocytoma in 47 (3.6%) clones, 20 of them having been located in
      2p, 10 in 2q, and 11 in 3q. An unsupervised hierarchical clustering analysis
      classified the cases into three clusters: one pilomyxoid astrocytoma patient into
      one cluster, two pilomyxoid astrocytoma patients into another cluster, and six
      pilocytic astrocytoma patients and one pilomyxoid astrocytoma patient into the
      third cluster. In conclusion, the presence of mixed-form pilomyxoid astrocytoma,
      the acquisition of pilocytic astrocytoma features in a recurrent tumor in pure
      form pilomyxoid astrocytoma, and the above results of the genome-wide gene copy
      number analysis suggest that pilomyxoid astrocytoma might be a pathologically and
      genetically related, aggressive variant of pilocytic astrocytoma with partially
      different genetic alterations.

PMID- 18622385
TI  - Global DNA hypomethylation in intratubular germ cell neoplasia and seminoma, but
      not in nonseminomatous male germ cell tumors.
AB  - Alterations in methylation of CpG dinucleotides at the 5 position of
      deoxycytidine residues (5(m)C) are a hallmark of cancer cells, including
      testicular germ cell tumors. Virtually all testicular germ cell tumors are
      believed to be derived from intratubular germ cell neoplasia unclassified
      (IGCNU), which is thought to arise from primordial germ cells. Prior studies
      revealed that seminomas contain reduced levels of global DNA methylation as
      compared with nonseminomatous germ cell tumors. Smiraglia et al have proposed a
      model whereby seminomas arise from IGCNU cells derived from primordial germ cells
      that have undergone 5(m)C erasure, and nonseminomas arise from IGCNU cells
      derived from primordial germ cells that have already undergone de novo
      methylation after the original erasure of methylation and contain normal 5(m)C
      levels. Yet the methylation status of IGCNU has not been determined previously.
      We used immunohistochemical staining against 5(m)C to evaluate global methylation
      in IGCNU and associated invasive testicular germ cell tumors. Strikingly,
      staining for 5(m)C was undetectable (or markedly reduced) in the majority of
      IGCNU and seminomas, yet there was robust staining in nonseminomatous germ cell
      tumors. The lack of staining for 5(m)C in IGCNU and seminomas was also found in
      mixed germ cell tumors containing both seminomatous and nonseminomatous
      components. Lack of 5(m)C staining was not related to a lack of the maintenance
      methyltransferase (DNA methyltransferase 1) protein. We conclude that testicular
      germ cell tumors are derived in most cases from IGCNU cells that have undergone
      developmentally programmed 5(m)C erasure and that the degree of subsequent de
      novo methylation is most closely related to the differentiation state of the
      neoplastic cells. That is, IGCNU cells and seminoma cells remain unmethylated,
      whereas all other histological types appear to arise after de novo methylation.

PMID- 18622386
TI  - N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar
      cholangiocarcinomas.
AB  - As a definite immunoprofile of this tumor is missing, the histopathologic
      diagnosis of intrahepatic cholangiocarcinoma is difficult. The aim of this study
      was to explore E- and N-cadherin expressions in intrahepatic bile duct tumors,
      and to determine their potential interest in differential diagnosis. Normal liver
      tissue, 5 cirrhosis with ductular reaction, 5 focal nodular hyperplasia, 5 bile
      duct hamartomas, 5 bile duct adenomas, and 45 intrahepatic cholangiocarcinomas
      from Caucasian patients were studied. Tissue-microarrays including 20 esophageal,
      86 gastric, 8 small bowel, 64 colonic, 18 pancreatic, 6 gallbladder, and 7
      extrahepatic biliary tract adenocarcinomas, 22 hepatocellular carcinomas, and
      normal tissues were constructed. Immunohistochemistry was performed using E
      cadherin, N-cadherin, NCAM, Hep Par1, and cytokeratins 7, 19 and 20. Immunoblot
      analysis of frozen liver tissues was performed to control the specificity of E-
      and N-cadherin antibodies used. In normal liver, epithelial cells of intrahepatic
      bile ducts, whatever their caliber, as well as hepatocytes, coexpressed E- and N
      cadherins at their plasma membranes. In cirrhosis, ductular reactions completely
      expressed E- and N-cadherins. All the benign lesions and 30 of the 45
      intrahepatic cholangiocarcinomas (23/29 peripheral and 7/16 hilar) also expressed
      N-cadherin. E-cadherin was detected in all the lesions. The expression of N
      cadherin at the plasma membrane of tumor cells was significantly more frequent in
      peripheral than in hilar intrahepatic cholangiocarcinomas (P=0.003). Among
      noncholangiocarcinomas, only 1% gastric and 66% gallbladder adenocarcinomas and
      all the hepatocellular carcinomas expressed N-cadherin at the membrane of tumor
      cells. Finally, for the diagnosis of intrahepatic cholangiocarcinomas, the
      specificity value of membranous expression of N-cadherin was 88%, whereas that of
      the combination cytokeratin 7/membranous N-cadherin was 98%. In the
      gastrointestinal and liver tract, membranous N-cadherin is restricted to the
      hepatocytes and intrahepatic biliary cells. In combination with cytokeratin 7 and
      Hep Par1, N-cadherin is a reliable tool for the histopathological diagnosis of
      primary hepatic tumors.

PMID- 18622387
TI  - Cartilaginous features in matrix-producing carcinoma of the breast: four cases
      report with histochemical and immunohistochemical analysis of matrix molecules.
AB  - Matrix-producing carcinoma of the breast is a well-established entity in the
      group of metaplastic carcinoma, which is histologically characterized by
      myxochondroid matrix formation and is extremely rare. We describe here four
      additional cases of matrix-producing carcinoma of the breast. All cases of matrix
      producing carcinoma show nest-like, sheet-like, and cord-like growth of tumor
      cells with cellular atypia, in addition to scattered cancer cells within myxoid
      or myxohyalinous stroma. Three of four cases showed an acellular or oligocellular
      matrix-rich zone in the center of the tumor. Immunohistochemically, cancer cells
      of all cases were positive for cytokeratins and epithelial membrane antigens and
      partially positive for sox9 and p63. Aggrecan and type II collagen, which are
      cartilage-specific matrix molecules, were deposited in the stroma of all cases.
      Type I and type IV collagens were also deposited on the stroma of all cases.
      These findings suggest that, although cancer cells of matrix-producing carcinoma
      of the breast are epithelial, they transdifferentiate to chondrocyte-like cells
      and produce cartilage-specific matrix molecules, which are useful markers for
      diagnosing matrix-producing carcinoma.

PMID- 18622388
TI  - The auxin influx carrier LAX3 promotes lateral root emergence.
AB  - Lateral roots originate deep within the parental root from a small number of
      founder cells at the periphery of vascular tissues and must emerge through
      intervening layers of tissues. We describe how the hormone auxin, which
      originates from the developing lateral root, acts as a local inductive signal
      which re-programmes adjacent cells. Auxin induces the expression of a previously
      uncharacterized auxin influx carrier LAX3 in cortical and epidermal cells
      directly overlaying new primordia. Increased LAX3 activity reinforces the auxin
      dependent induction of a selection of cell-wall-remodelling enzymes, which are
      likely to promote cell separation in advance of developing lateral root
      primordia.

PMID- 18622389
TI  - An integrated platform of genomic assays reveals small-molecule bioactivities.
AB  - Bioactive compounds are widely used to modulate protein function and can serve as
      important leads for drug development. Identifying the in vivo targets of these
      compounds remains a challenge. Using yeast, we integrated three genome-wide gene
      dosage assays to measure the effect of small molecules in vivo. A single TAG
      microarray was used to resolve the fitness of strains derived from pools of (i)
      homozygous deletion mutants, (ii) heterozygous deletion mutants and (iii) genomic
      library transformants. We demonstrated, with eight diverse reference compounds,
      that integration of these three chemogenomic profiles improves the sensitivity
      and specificity of small-molecule target identification. We further dissected the
      mechanism of action of two protein phosphatase inhibitors and in the process
      developed a framework for the rational design of multidrug combinations to
      sensitize cells with specific genotypes more effectively. Finally, we applied
      this platform to 188 novel synthetic chemical compounds and identified both
      potential targets and structure-activity relationships.

PMID- 18622390
TI  - Synaptotagmin arrests the SNARE complex before triggering fast, efficient
      membrane fusion in response to Ca2+.
AB  - Neuronal communication is mediated by Ca(2+)-triggered fusion of transmitter
      filled synaptic vesicles with the presynaptic plasma membrane. Synaptotagmin I
      functions as a Ca(2+) sensor that regulates exocytosis, whereas soluble N
      ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE)
      proteins in the vesicle and target membrane assemble into complexes that directly
      catalyze bilayer fusion. Here we report that, before the Ca(2+) trigger,
      synaptotagmin interacts with SNARE proteins in the target membrane to halt SNARE
      complex assembly at a step after donor vesicles attach, or dock, to target
      membranes. This results in fusion complexes that, when subsequently triggered by
      Ca(2+), drive rapid, highly efficient lipid mixing. Ca(2+)-independent
      interactions with SNAREs also predispose synaptotagmin to selectively penetrate
      the target membrane in response to Ca(2+); we demonstrate that Ca(2+)
      synaptotagmin must insert into the target membrane to accelerate SNARE-catalyzed
      fusion. These findings demonstrate that Ca(2+) converts synaptotagmin from a
      clamp to a trigger for exocytosis.

PMID- 18622391
TI  - A comprehensive library of histone mutants identifies nucleosomal residues
      required for H3K4 methylation.
AB  - Methylation of histone 3 lysine 4 (H3K4) by yeast Set1-COMPASS requires prior
      monoubiquitination of histone H2B. To define whether other residues within the
      histones are also required for H3K4 methylation, we systematically generated a
      complete library of the alanine substitutions of all of the residues of the four
      core histones in Saccharomyces cerevisiae. From this study we discovered that 18
      residues within the four histones are essential for viability on complete growth
      media. We also identified several cis-regulatory residues on the histone H3 N
      terminal tail, including histone H3 lysine 14 (H3K14), which are required for
      normal levels of H3K4 trimethylation. Several previously uncharacterized trans
      regulatory residues on histones H2A and H2B form a patch on nucleosomes and are
      required for methylation mediated by COMPASS. This library will be a valuable
      tool for defining the role of histone residues in processes requiring chromatin.

PMID- 18622392
TI  - Fission yeast SWI/SNF and RSC complexes show compositional and functional
      differences from budding yeast.
AB  - SWI/SNF chromatin-remodeling complexes have crucial roles in transcription and
      other chromatin-related processes. The analysis of the two members of this class
      in Saccharomyces cerevisiae, SWI/SNF and RSC, has heavily contributed to our
      understanding of these complexes. To understand the in vivo functions of SWI/SNF
      and RSC in an evolutionarily distant organism, we have characterized these
      complexes in Schizosaccharomyces pombe. Although core components are conserved
      between the two yeasts, the compositions of S. pombe SWI/SNF and RSC differ from
      their S. cerevisiae counterparts and in some ways are more similar to metazoan
      complexes. Furthermore, several of the conserved proteins, including actin-like
      proteins, are markedly different between the two yeasts with respect to their
      requirement for viability. Finally, phenotypic and microarray analyses identified
      widespread requirements for SWI/SNF and RSC on transcription including strong
      evidence that SWI/SNF directly represses iron-transport genes.

PMID- 18622393
TI  - Hypomethylation of multiple imprinted loci in individuals with transient neonatal
      diabetes is associated with mutations in ZFP57.
AB  - We have previously described individuals presenting with transient neonatal
      diabetes and showing a variable pattern of DNA hypomethylation at imprinted loci
      throughout the genome. We now report mutations in ZFP57, which encodes a zinc
      finger transcription factor expressed in early development, in seven pedigrees
      with a shared pattern of mosaic hypomethylation and a conserved range of clinical
      features. This is the first description of a heritable global imprinting disorder
      that is compatible with life.

PMID- 18622394
TI  - Critical function of Prdm14 for the establishment of the germ cell lineage in
      mice.
AB  - Specification of germ cell fate is fundamental in development and heredity.
      Recent evidence indicates that in mice, specification of primordial germ cells
      (PGCs), the common source of both oocytes and spermatozoa, occurs through the
      integration of three key events: repression of the somatic program, reacquisition
      of potential pluripotency and ensuing genome-wide epigenetic reprogramming. Here
      we provide genetic evidence that Prdm14, a PR domain-containing transcriptional
      regulator with exclusive expression in the germ cell lineage and pluripotent cell
      lines, is critical in two of these events, the reacquisition of potential
      pluripotency and successful epigenetic reprogramming. In Prdm14 mutants, the
      failure of these two events manifests even in the presence of Prdm1 (also known
      as Blimp1), a key transcriptional regulator for PGC specification. Our combined
      evidence demonstrates that Prdm14 defines a previously unknown genetic pathway,
      initiating independently from Prdm1, for ensuring the launching of the mammalian
      germ cell lineage.

PMID- 18622395
TI  - Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility
      to knee osteoarthritis.
AB  - Susceptibility to osteoarthritis, the most common human arthritis, is known to be
      influenced by genetic factors. Through a genome-wide association study using
      approximately 100,000 SNPs, we have identified a previously unknown gene on
      chromosome 3p24.3, DVWA, which is associated with susceptibility to knee
      osteoarthritis. Expressed specifically in cartilage, DVWA encodes a 276-amino
      acid protein with two regions corresponding to the von Willebrand factor type A
      domain (VWA domain). Several DVWA SNPs are significantly associated with knee
      osteoarthritis in two independent Japanese case-control cohorts. This association
      was replicated in a Japanese population cohort and a Han Chinese case-control
      cohort (combined P = 7.3 x 10(-11)). DVWA protein binds to beta-tubulin, and the
      binding is influenced by two highly associated missense SNPs (rs11718863 and
      rs7639618) located in the VWA domain. The Tyr169-Cys260 isoform of DVWA, which is
      overrepresented in knee osteoarthritis, showed weaker interaction. Our findings
      reveal a new paradigm for study of osteoarthritis etiology and pathogenesis.

PMID- 18622396
TI  - Improving membrane voltage measurements using FRET with new fluorescent proteins.
AB  - We used two new coral fluorescent proteins as fluorescence resonance energy
      transfer (FRET) donor and acceptor to develop a voltage sensor, named Mermaid,
      that displays approximately 40% changes in emission ratio per 100 mV, allowing
      for direct visualization of electrical activities in cultured excitable cells.
      Notably, Mermaid has fast on-off kinetics at warm (approximately 33 degrees C)
      temperatures and can report voltage spikes comparable to action potentials.

PMID- 18622397
TI  - A comprehensive strategy enabling high-resolution functional analysis of the
      yeast genome.
AB  - Functional genomic studies in Saccharomyces cerevisiae have contributed
      enormously to our understanding of cellular processes. Their full potential,
      however, has been hampered by the limited availability of reagents to
      systematically study essential genes and the inability to quantify the small
      effects of most gene deletions on growth. Here we describe the construction of a
      library of hypomorphic alleles of essential genes and a high-throughput growth
      competition assay to measure fitness with unprecedented sensitivity. These tools
      dramatically increase the breadth and precision with which quantitative genetic
      analysis can be performed in yeast. We illustrate the value of these approaches
      by using genetic interactions to reveal new relationships between chromatin
      modifying factors and to create a functional map of the proteasome. Finally, by
      measuring the fitness of strains in the yeast deletion library, we addressed an
      enigma regarding the apparent prevalence of gene dispensability and found that
      most genes do contribute to growth.

PMID- 18622398
TI  - Yeast Barcoders: a chemogenomic application of a universal donor-strain
      collection carrying bar-code identifiers.
AB  - The ability to perform complex bioassays in parallel enables experiments that are
      otherwise impossible because of throughput and cost constraints. For example,
      highly parallel chemical-genetic screens using pooled collections of thousands of
      defined Saccharomyces cerevisiae gene deletion strains are feasible because each
      strain is bar-coded with unique DNA sequences. It is, however, time-consuming and
      expensive to individually bar-code individual strains. To provide a simple and
      general method of barcoding yeast collections, we built a set of donor strains,
      called Barcoders, with unique bar codes that can be systematically transferred to
      any S. cerevisiae collection. We applied this technology by generating a
      collection of bar-coded 'decreased abundance by mRNA perturbation' (DAmP) loss-of
      function strains comprising 87.1% of all essential yeast genes. These experiments
      validate both the Barcoders and the DAmP strain collection as useful tools for
      genome-wide chemical-genetic assays.

PMID- 18622399
TI  - Patches of face-selective cortex in the macaque frontal lobe.
AB  - In primates, specialized occipital-temporal face areas support the visual
      analysis of faces, but it is unclear whether similarly specialized areas exist in
      the frontal lobe. Using functional magnetic resonance imaging in alert macaques,
      we identified three discrete regions of highly face-selective cortex in ventral
      prefrontal cortex, one of which was strongly lateralized to the right hemisphere.
      These prefrontal face patches may constitute dedicated modules for retrieving and
      responding to facial information.

PMID- 18622400
TI  - Neurons born in the adult dentate gyrus form functional synapses with target
      cells.
AB  - Adult neurogenesis occurs in the hippocampus and the olfactory bulb of the
      mammalian CNS. Recent studies have demonstrated that newborn granule cells of the
      adult hippocampus are postsynaptic targets of excitatory and inhibitory neurons,
      but evidence of synapse formation by the axons of these cells is still lacking.
      By combining retroviral expression of green fluorescent protein in adult-born
      neurons of the mouse dentate gyrus with immuno-electron microscopy, we found
      output synapses that were formed by labeled terminals on appropriate target cells
      in the CA3 area and the hilus. Furthermore, retroviral expression of
      channelrhodopsin-2 allowed us to light-stimulate newborn granule cells and
      identify postsynaptic target neurons by whole-cell recordings in acute slices.
      Our structural and functional evidence indicates that axons of adult-born granule
      cells establish synapses with hilar interneurons, mossy cells and CA3 pyramidal
      cells and release glutamate as their main neurotransmitter.

PMID- 18622401
TI  - Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and
      antipsychotic drugs.
AB  - DARPP-32 is a dual-function protein kinase/phosphatase inhibitor that is involved
      in striatal signaling. The phosphorylation of DARPP-32 at threonine 34 is
      essential for mediating the effects of both psychostimulant and antipsychotic
      drugs; however, these drugs are known to have opposing behavioral and clinical
      effects. We hypothesized that these drugs exert differential effects on
      striatonigral and striatopallidal neurons, which comprise distinct output
      pathways of the basal ganglia. To directly test this idea, we developed bacterial
      artificial chromosome transgenic mice that allowed the analysis of DARPP-32
      phosphorylation selectively in striatonigral and striatopallidal neurons. Using
      this new methodology, we found that cocaine, a psychostimulant, and haloperidol,
      a sedation-producing antipsychotic, exert differential effects on DARPP-32
      phosphorylation in the two neuronal populations that can explain their opposing
      behavioral effects. Furthermore, we found that a variety of drugs that target the
      striatum have cell type-specific effects that previous methods were not able to
      discern.

PMID- 18622402
TI  - The stress hormone corticosterone conditions AMPAR surface trafficking and
      synaptic potentiation.
AB  - Corticosterone facilitates hippocampal glutamate transmission, but the cellular
      pathways by which AMPA receptor (AMPAR) signaling is adjusted remain elusive.
      Single quantum-dot imaging in live rat hippocampal neurons revealed that
      corticosterone triggers, via distinct corticosteroid receptors, time-dependent
      increases in GluR2-AMPAR surface mobility and synaptic surface GluR2 content.
      Furthermore, corticosterone potentiates the increase of synaptic surface GluR2
      contents by a chemical long-term potentiation stimulus, revealing the influence
      that corticosterone has on AMPAR trafficking.

PMID- 18622404
TI  - Ordered silicon vacancies in the framework structure of the zeolite catalyst SSZ
      74.
AB  - Physico-chemical characterization of the high-silica zeolite catalyst SSZ-74
      (ref. 1) suggested that it, like the related materials TNU-9 (ref. 2) and IM-5
      (ref. 3), has a multidimensional 10-ring channel system. Such pore systems are
      ideal for many petrochemical applications, and indeed SSZ-74 has been shown to be
      a good catalyst for a wide variety of reactions. The elucidation of its framework
      structure, however, proved to be difficult. Comparable problems were encountered
      with TNU-9 and IM-5, which were synthesized with related structure-directing
      agents. Their framework structures, which are the two most complex ones known,
      both have 24 Si atoms in the asymmetric unit, and were finally solved by
      combining high-resolution powder diffraction data with information derived from
      high-resolution electron microscopy images. Therefore, a similar approach, using
      the powder charge-flipping algorithm to combine the two types of data and
      molecular modelling to help to locate the structure-directing agent, was applied
      to SSZ-74. This procedure eventually revealed a most unusual 23-Si-atom framework
      structure (|(C(16)H(34)N(2))(4)&Si(92)(4)O(184)(OH)(8)]) with ordered Si
      vacancies.

PMID- 18622403
TI  - Adenovirus-mediated gene expression imaging to directly detect sentinel lymph
      node metastasis of prostate cancer.
AB  - The accurate assessment of nodal involvement in prostate cancer is crucial to
      planning treatment, yet there is a shortage of noninvasive imaging techniques
      capable of visualizing nodal lesions directly. This study demonstrates the
      feasibility of using recombinant human adenoviral vectors to detect nodal
      metastases in a human prostate cancer model. This was achieved by the prostate
      restricted expression of optical and positron emission tomography (PET) imaging
      reporter genes by the viral vector coupled with the innate lymphotropic
      properties of adenovirus. We show that peritumoral administration of these
      vectors results in the direct detection of reporter gene expression in metastatic
      lesions within sentinel lymph nodes. Notably, this approach parallels the current
      lymphoscintigraphy method but enables the direct PET visualization of sentinel
      lymph node metastases, eliminating the need for invasive lymphadenectomy. These
      findings may lead to more effective diagnostic and therapeutic strategies for
      individuals with advanced-stage prostate cancer.

PMID- 18622405
TI  - The role of metal nanoparticles and nanonetworks in alloy degradation.
AB  - Oxide scale, which is essential to protect structural alloys from high
      temperature degradation such as oxidation, carburization and metal dusting, is
      usually considered to consist simply of oxide phases. Here, we report on a
      nanobeam X-ray and magnetic force microscopy investigation that reveals that the
      oxide scale actually consists of a mixture of oxide materials and metal
      nanoparticles. The metal nanoparticles self-assemble into nanonetworks, forming
      continuous channels for carbon transport through the oxide scales. To avoid the
      formation of these metallic particles in the oxide scale, alloys must develop a
      scale without spinel phase. We have designed a novel alloy that has been tested
      in a high-carbon-activity environment. Our results show that the incubation time
      for carbon transport through the oxide scale of the new alloy is more than an
      order of magnitude longer compared with commercial alloys with similar chromium
      content.

PMID- 18622406
TI  - Resonant bonding in crystalline phase-change materials.
AB  - The identification of materials suitable for non-volatile phase-change memory
      applications is driven by the need to find materials with tailored properties for
      different technological applications and the desire to understand the scientific
      basis for their unique properties. Here, we report the observation of a
      distinctive and characteristic feature of phase-change materials. Measurements of
      the dielectric function in the energy range from 0.025 to 3 eV reveal that the
      optical dielectric constant is 70-200% larger for the crystalline than the
      amorphous phases. This difference is attributed to a significant change in
      bonding between the two phases. The optical dielectric constant of the amorphous
      phases is that expected of a covalent semiconductor, whereas that of the
      crystalline phases is strongly enhanced by resonant bonding effects. The
      quantification of these is enabled by measurements of the electronic
      polarizability. As this bonding in the crystalline state is a unique fingerprint
      for phase-change materials, a simple scheme to identify and characterize
      potential phase-change materials emerges.

PMID- 18622407
TI  - Towards nanomicrobiology using atomic force microscopy.
AB  - At the cross-roads of nanoscience and microbiology, the nanoscale analysis of
      microbial cells using atomic force microscopy (AFM) is an exciting, rapidly
      evolving research field. Over the past decade, there has been tremendous progress
      in our use of AFM to observe membrane proteins and live cells at high resolution.
      Remarkable advances have also been made in applying force spectroscopy to
      manipulate single membrane proteins, to map surface properties and receptor sites
      on cells and to measure cellular interactions at the single-cell and single
      molecule levels. In addition, recent developments in cantilever nanosensors have
      opened up new avenues for the label-free detection of microorganisms and
      bioanalytes.

PMID- 18622409
TI  - Oleanolic acid induces relaxation and calcium-independent release of endothelium
      derived nitric oxide.
AB  - BACKGROUND AND PURPOSE: The present study investigated the mechanisms by which
      oleanolic acid, a component of olive oil, increases release of nitric oxide (NO).
      EXPERIMENTAL APPROACH: Measurements of isometric tension, NO concentration, or
      endothelial cell calcium were made in rat isolated mesenteric arteries.
      Immunoblotting for endothelial NOS (eNOS) and Akt kinase were performed in
      primary cultures of human umbilical vein endothelial cells (HUVECs). KEY RESULTS:
      Oleanolic acid (3-30 microM) evoked endothelium-dependent relaxations in
      noradrenaline-contracted rat superior and small mesenteric arteries. In rat
      superior mesenteric arteries, oleanolic acid induced simultaneous increases in NO
      concentration and relaxation, and these responses were inhibited by an inhibitor
      of NOS, asymmetric dimethyl-L-arginine (300 microM) and by the NO scavenger,
      oxyhaemoglobin (10 microM). Oleanolic acid-evoked NO increases were not reduced
      in Ca(2+)-free solution and in the presence of an inhibitor of endoplasmic
      reticulum calcium-ATPase, thapsigargin (1 microM). Oleanolic acid evoked
      relaxation without changes in endothelial cell calcium, but decreased smooth
      muscle calcium in arterial segments. Oleanolic acid failed to increase calcium in
      HUVECs, but increased time-dependently phosphorylation of Akt kinase at
      Serine(473) (Akt-Ser(473)) and eNOS at Serine(1177) (eNOS-Ser(1177)), which was
      attenuated by inhibitors of phosphoinositide-3-kinase. CONCLUSIONS AND
      IMPLICATIONS: This study provides direct evidence that a component of olive oil,
      oleanolic acid, activated endothelium-dependent release of NO and decreased
      smooth muscle cell calcium followed by relaxation. The oleanolic acid-evoked
      endothelium-derived NO release was independent of endothelial cell calcium and
      involved phosphoinositide-3-kinase-dependent phosphorylation of Akt-Ser(473)
      followed by phosphorylation of eNOS-Ser(1177).

PMID- 18622408
TI  - Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced
      hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors.
AB  - BACKGROUND AND PURPOSE: Salvinorin A, the active component of the hallucinogenic
      herb Salvia divinorum, inhibits intestinal motility through activation of kappa
      opioid receptors (KORs). However, this compound may have target(s) other than the
      KORs in the inflamed gut. Because intestinal inflammation upregulates cannabinoid
      receptors and endogenous cannabinoids, in the present study we investigated the
      possible involvement of the endogenous cannabinoid system in salvinorin A-induced
      delay in motility in the inflamed gut. EXPERIMENTAL APPROACH: Motility in vivo
      was measured by evaluating the distribution of a fluorescent marker along the
      small intestine; intestinal inflammation was induced by the irritant croton oil;
      direct or indirect activity at cannabinoid receptors was evaluated by means of
      binding, enzymic and cellular uptake assays. KEY RESULTS: Salvinorin A as well as
      the KOR agonist U-50488 reduced motility in croton oil treated mice. The
      inhibitory effect of both salvinorin A and U-50488 was counteracted by the KOR
      antagonist nor-binaltorphimine and by the cannabinoid CB(1) receptor antagonist
      rimonabant. Rimonabant, however, did not counteract the inhibitory effect of
      salvinorin A on motility in control mice. Binding experiments showed very weak
      affinity of salvinorin A for cannabinoid CB(1) and CB(2) and no inhibitory effect
      on 2-arachidonoylglycerol and anandamide hydrolysis and cellular uptake.
      CONCLUSIONS AND IMPLICATIONS: The inhibitory effect of salvinorin A on motility
      reveals a functional interaction between cannabinoid CB(1) receptors and KORs in
      the inflamed--but not in the normal--gut in vivo.

PMID- 18622410
TI  - Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of
      cognitive impairment in the rat.
AB  - BACKGROUND AND PURPOSE: The beneficial effect of 5-HT6 receptor antagonism in
      cognition remains controversial. This study has been undertaken to reassess the
      cognition enhancing properties of acute vs subchronic treatment with the
      selective 5-HT6 receptor antagonist SB-271046 in unimpaired rats, as well as
      against scopolamine (cholinergic-) or MK-801 (glutamatergic-mediated) deficits.
      EXPERIMENTAL APPROACH: The Morris water maze was used, measuring behaviour
      acquisition and retention, and swim speed. Other behavioural measures included
      yawning and motor activity. SB-271046 was given acutely before each trial or
      subchronically for 7 days before the trials. The AChE inhibitor galanthamine was
      also used alone or in combination with SB-271046. KEY RESULTS: Subchronic
      treatment with SB-271046 improved acquisition in the Morris water maze, while the
      acute treatment only improved retention. Neither acute nor subchronic SB-271046
      treatment reversed scopolamine-induced learning deficits. MK-801 induced learning
      impairment associated with a behavioural syndrome, reversed by acute, but not
      subchronic, SB-271046 treatment. Interestingly, combined treatment with
      galanthamine and SB-271046 reversed the scopolamine- or MK-801-induced learning
      impairments. Subchronic treatment with SB-271046 did not modify motor activity or
      the increased number of yawns, a cholinergic-mediated behaviour, induced by
      single administration of SB-271046. CONCLUSIONS AND IMPLICATIONS: These data
      suggest a potential therapeutic role of 5-HT6 receptor antagonists such as SB
      271046, alone or in combination with galanthamine, in the treatment of cognitive
      dysfunction, such as those seen in Alzheimer's disease and schizophrenia.

PMID- 18622411
TI  - Contemporary analysis of the influence of acute kidney injury after reduced
      intensity conditioning haematopoietic cell transplantation on long-term survival.
AB  - We evaluated retrospectively the incidence of acute kidney injury (AKI), defined
      by risk, injury, failure, loss and end-stage kidney disease (RIFLE) and its
      influence on long-term survival, in 82 patients aged 18-60 years who underwent a
      reduced intensity conditioning (RIC) haematopoietic cell transplantation (HCT).
      Patients (53.6%) developed AKI after HCT: 25% were on risk, 45.5% on injury and
      29.5% on failure. In all, 64 patients survived after 100 days of post transplant
      and were available for long-term survival analysis. At follow-up, 43.7% of
      patients died. A 5-year overall survival of AKI patients was 41.6% as compared
      with 67.1% for those who did not develop AKI (P=0.028), and decreased according
      to AKI severity (risk, 55.6%; injury plus failure, 33.3%; P=0.045). After
      adjusting for age, history of cardiovascular disease, high-risk disease and
      chronic GVHD, AKI predicted 5-year overall mortality (AKI: adjusted hazards ratio
      (AHR), 2.36, 95% CI: 1.03-5.37; P=0.041). Moreover, moderate and severe AKI
      (injury plus failure) was also associated with an increased 5-year overall
      mortality (injury plus failure: AHR, 1.64, 95% CI: 1.06-2.54; P=0.024). According
      to RIFLE, 53.6% of patients had AKI after RIC HCT. Such patients have poor long
      term survival, particularly in moderate or severe AKI.

PMID- 18622412
TI  - Fanconi Anemia patient with AML1 gene amplification and monosomy 7 in pre
      transplant myelodysplasia (MDS) relapsing 7 years after successful allo-SCT.

PMID- 18622413
TI  - Reduced intensity HLA-haploidentical BMT with post transplantation
      cyclophosphamide in nonmalignant hematologic diseases.
AB  - Allogeneic blood or marrow transplantation (BMT) is potentially curative for a
      variety of life-threatening nonmalignant hematologic diseases such as paroxysmal
      nocturnal hemoglobinuria (PNH) and hemoglobinopathies. The application of BMT to
      treat these disorders is limited by the lack of suitable donors and often end
      organ damage from the underlying disease. We treated three patients with
      thrombotic PNH, one of whom also had sickle cell disease, with a
      nonmyeloablative, HLA-haploidentical BMT with post-transplant CY. Rapid
      engraftment without GVHD occurred in two of the patients, including the patient
      with sickle cell disease. Both patients are disease free with full donor
      chimerism and require no immunosuppressive therapy, with follow-up of 1 and 4
      years, respectively. Nonmyeloablative, HLA-haploidentical BMT with post
      transplant CY is a promising approach for patients with life-threatening
      nonmalignant hematologic disease who lack an HLA-matched sibling donor.

PMID- 18622414
TI  - Long-term progression-free survival after early autologous transplantation for
      mantle-cell lymphoma.
AB  - Autologous hematopoietic progenitor SCT (HPCT) has been studied both as a
      consolidative and salvage maneuver in mantle-cell lymphoma (MCL), and may improve
      failure-free survival rates as well as overall survival. We describe 21 patients
      with MCL who received autologous HPCT at Emory University Hospital as part of the
      primary treatment strategy. Sixteen patients were in CR1 and five in PR1 at the
      time of HPCT. The most commonly used induction chemotherapy was the hyper-CVAD
      (cyclophosphamide, vincristine, doxorubicin and dexamethasone) regimen with or
      without rituximab. At the last follow-up, 17 patients were in continuous CR, and
      there were four relapses. There were no transplant-related deaths. With a median
      follow-up of 54 months from HPCT, 5-year progression-free survival and overall
      survival are 73% and 76%, respectively. Our retrospective analysis provides the
      longest follow-up to date for patients with MCL who received an autologous HPCT
      as part of primary treatment. This lengthy follow-up helps define the natural
      course of MCL after autologous transplantation.

PMID- 18622415
TI  - Treatment of adult AML with t(6;11)(q27;q23) by allogeneic hematopoietic SCT in
      the first CR.

PMID- 18622416
TI  - Breakthrough Rhizopus infection on posaconazole prophylaxis following allogeneic
      stem cell transplantation.

PMID- 18622417
TI  - BK virus encephalitis in an allogeneic hematopoietic stem cell recipient.

PMID- 18622418
TI  - Folinic acid administration following MTX as prophylaxis for GVHD in allogeneic
      HSCT centres in Australia and New Zealand.
AB  - The use of MTX for GVHD prophylaxis may be associated with significant toxicity,
      including hepatotoxicity, graft failure and mucositis. Folinic acid may be
      involved in the amelioration of MTX toxicity. There is, however, no consensus
      regarding its use. A survey was conducted in Australian and New Zealand
      transplant centres (n=22) regarding the use of folinic acid following MTX in the
      transplant setting. Of 18 participating transplant centres, 12 (66%) used folinic
      acid following MTX--8 (44%) routinely and 4 (22%) only in the presence of
      significant mucositis. Those centres that did not use routine dosing of folinic
      acid post transplant chose not to do so on the grounds that they believed that it
      was not efficacious or may increase the risk of GVHD. Grading of mucositis was
      inconsistently done. There is wide variation in the use of folinic acid following
      HSCT. Folinic acid is infrequently used in the adult transplant setting or is
      used after mucositis is already apparent, practices that appear to run counter to
      available clinical evidence and to pharmacological data. Further research is
      required to conclusively determine whether folinic acid has any benefit in the
      post-BMT setting.

PMID- 18622420
TI  - Factors influencing catheter-related infections in the Dutch multicenter study on
      high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer
      patients.
AB  - Neutropenia following high-dose chemotherapy leads to a high incidence of
      infectious complications, of which central venous catheter-related infections
      predominate. Catheter-related infections and associated risk factors in 392
      patients participating in a randomized adjuvant breast cancer trial and assigned
      to receive high-dose chemotherapy and peripheral stem-cell reinfusion were
      evaluated. Median catheter dwell time was 25 days (range 1-141). Catheter-related
      infections were seen in 28.3% of patients (11 infections per 1000 catheter-days).
      Coagulase-negative staphylococci were found in 104 of 186 positive blood cultures
      (56%). No systemic fungal infections occurred. Cox regression analysis showed
      that duration of neutropenia >10 days (P=0.04), using the catheter for both stem
      cell apheresis and high-dose chemotherapy (P= <0.01), and use of total parenteral
      nutrition (TPN, P=0.04) were predictive for catheter-related infections. In
      conclusion, a high incidence of catheter-related infections after high-dose
      chemotherapy was seen related to duration of neutropenia, use of the catheter for
      both stem-cell apheresis and high-dose chemotherapy, and use of TPN. Selective
      use and choice of catheters could lead to a substantial reduction of catheter
      related infectious complications.

PMID- 18622419
TI  - Optimizing BM harvesting from normal adult donors.
AB  - The experience at a single institution of BM harvesting (BMH) in general
      anesthetic for allogeneic transplantation from 49 healthy adult donors since
      March 2002 is presented in detail, together with an analysis of all the donor
      complications. In this study, we analyzed the advantages through the change from
      an aspiration needle with one hole (group A, n=18) to a system with additional
      five side holes (group B, n=31) in April 2005 for faster aspiration of large
      volumes of BM. In group B, the operation time was reduced by 50%, which is 12 min
      to date (1006 ml BM). Furthermore, the collection rate (volume BM/time) was
      significantly increased, namely to 81.9 ml/min in group B. The yields of total
      nucleated cells and CD34+ cells are nearly identical and adequate in both
      systems. The proportion of donors treated as day cases--that is, able to be
      discharged on the same day as the procedure--was 56% in group A and 81% in group
      B. There was no significant operative site morbidity. BMH accomplished by trained
      personal is a safe procedure for healthy adult donors on an outpatient basis as
      standard in our collection center.

PMID- 18622421
TI  - Autologous HSC transplant in t-MDS/AML using cells harvested prior to the
      development of the secondary malignancy.

PMID- 18622422
TI  - Successful autologous hematopoietic progenitor cell transplantation in a patient
      with an isoantibody against CD36 (glycoprotein IV, Naka).

PMID- 18622423
TI  - Determination of initial i.v. CYA dosage to achieve target AUC values in
      pediatric hematopoietic stem cell transplant patients.
AB  - In solid organ transplantation, CYA dosing is based on the area under the
      concentration vs time curve (AUC(inf)). This study aimed to develop a guideline
      for the initial i.v. CYA dose for pediatric hematopoietic SCT (HSCT) patients to
      achieve the target AUC(inf) recommended in solid organ transplantation. Whole
      blood CYA concentrations were determined in 24 patients (0.5-16.9 years) after
      the first i.v. dose given over 2 h, 1 day before HSCT. The i.v. CYA dose
      predicted to achieve an AUC(inf) of 4200 microg x h/l was calculated for each
      patient and expressed as a function of each patient's actual weight and body
      surface area (BSA). In patients <or=9 and >9 years of age, the mean i.v. CYA dose
      predicted to achieve the target AUC was 2.6+/-0.94 and 2.1+/-1.21 mg/kg,
      respectively. When these doses were expressed in terms of BSA, the mean dose was
      65+/-23.1 and 68+/-35.0 mg/m(2) in children <or=9 and >9 years of age,
      respectively. In children 0.5-17 years of age undergoing HSCT, we recommend an
      initial i.v. CYA dose of 65 mg/m(2) infused over 2 h to achieve an AUC(inf) of
      approximately 4200 microg x h/l.

PMID- 18622424
TI  - Mixed donor chimaerism in recipient fingernails following reduced-intensity
      conditioning haematopoietic SCT.

PMID- 18622425
TI  - Matrix metalloproteinase-11/stromelysin-3 exhibits collagenolytic function
      against collagen VI under normal and malignant conditions.
AB  - The substrate of matrix metalloproteinase 11 (MMP11) remains unknown. We have
      recently shown that MMP11 is a negative regulator of adipogenesis, able to reduce
      and even to revert mature adipocyte differentiation. Here, we have used mouse
      3T3L1 cells and human U87MG and SaOS cells to show that MMP11 cleaves the native
      alpha3 chain of collagen VI, which is an adipocyte-related extracellular matrix
      component. It is known that extracellular proteolytic processing of this chain is
      required for correct collagen VI folding. Interestingly, MMP11-deficient fat
      tissue is less cohesive and exhibits collagen VI alteration, dramatic adipocyte
      plasma and basement membrane abnormalities and lipid leakage. MMP11 is thus
      required for correct collagen VI folding and therefore for fat tissue cohesion
      and adipocyte function. Both MMP11 and collagen VI favor tumor progression.
      Similar spatio-temporal overexpression at the adipocyte-cancer cell interface has
      been reported for the two proteins. MMP11-dependent collagen VI processing might
      therefore be expected to occur during malignancy. Accordingly, collagen VI no
      longer delineates adipocytes located at the invasive front of breast carcinomas.
      In conclusion, the native alpha3 chain of collagen VI constitutes a specific
      MMP11 substrate. This MMP11 collagenolytic activity is functional in fat tissue
      ontogenesis as well as during cancer invasive steps.

PMID- 18622426
TI  - A novel fusion 5'AFF3/3'BCL2 originated from a t(2;18)(q11.2;q21.33)
      translocation in follicular lymphoma.
AB  - Follicular lymphoma is the second most frequent type of non-Hodgkin's lymphoma in
      adults. The basic molecular defect consists of the t(14;18)(q32;q21)
      translocation, juxtaposing the B-cell lymphoma protein 2 gene BCL2 to the
      immunoglobulin heavy chain locus IGH@, and leading to the antiapoptotic BCL2
      protein overproduction. Variations in the t(14;18) are rare and can be classified
      into two categories: (i) simple variants, involving chromosomes 18 and 2, or 22,
      in which the fusion partner of BCL2 is the light-chain IGK@ or IGL@; (ii) complex
      variant translocations occurring among chromosomes 14, 18 and other chromosomes.
      We report a follicular lymphoma case showing BCL2 overexpression, detected by
      immunohistochemistry and real-time quantitative PCR, consequently to the
      formation of a novel fusion gene between the 5' of the lymphoid nuclear
      transcriptional activator gene AFF3 at 2q11.2, and the 3' of BCL2. This case
      shows evidence, for the first time, of BCL2 overexpression consequently to the
      fusion of BCL2 to a non-IG partner locus.

PMID- 18622427
TI  - Novel evidences for a tumor suppressor role of Rev3, the catalytic subunit of Pol
      zeta.
AB  - Cell cycle checkpoints and DNA repair act in concert to ensure DNA integrity
      during perturbation of normal replication or in response to genotoxic agents.
      Deficiencies in these protective mechanisms can lead to cellular transformation
      and ultimately tumorigenesis. Here we focused on Rev3, the catalytic subunit of
      the low-fidelity DNA repair polymerase zeta. Rev3 is believed to play a role in
      double-strand break (DSB)-induced DNA repair by homologous recombination. In line
      with this hypothesis, we show the accumulation of chromatin-bound Rev3 protein in
      late S-G2 of untreated cells and in response to clastogenic DNA damage as well as
      an gamma-H2AX accumulation in Rev3-depleted cells. Moreover, serine 995 of Rev3
      is in vitro phosphorylated by the DSB-inducible checkpoint kinase, Chk2. Our data
      also disclose a significant reduction of rev3 gene expression in 74 colon
      carcinomas when compared to the normal adjacent tissues. This reduced expression
      is independent of the carcinoma stages, suggesting that the downregulation of
      rev3 might have occurred early during tumorigenesis.

PMID- 18622428
TI  - ABINs inhibit EGF receptor-mediated NF-kappaB activation and growth of EGF
      receptor-overexpressing tumour cells.
AB  - The epidermal growth factor receptor (EGFR) is frequently overexpressed in
      various tumours of epidermal origin and is held responsible for tumourigenicity
      and tumour persistence. Increased nuclear factor (NF)-kappaB activity has been
      suggested to be involved in the malignant behaviour of EGFR-overexpressing cells.
      However, the mechanisms that regulate EGF-induced NF-kappaB activation are still
      largely unknown. Here we show that EGF can induce NF-kappaB-dependent gene
      expression independently from IkappaBalpha degradation or p100 processing in EGFR
      overexpressing HEK293T cells. Moreover, EGF-induced NF-kappaB activation could be
      inhibited by overexpression of ABINs, which were previously identified as
      intracellular inhibitors of tumour necrosis factor, interleukin-1 and
      lipopolysaccharide-induced NF-kappaB activation. Knockdown of ABIN-1 by RNA
      interference boosted the NF-kappaB response upon EGF stimulation. The C-terminal
      ubiquitin-binding domain containing region of ABINs was crucial and sufficient
      for NF-kappaB inhibition. Adenoviral gene transfer of ABINs reduced constitutive
      NF-kappaB activity as well as the proliferation of EGFR-overexpressing A431 and
      DU145 human carcinoma cells. Altogether, these results demonstrate an important
      role for an ABIN-sensitive non-classical NF-kappaB signalling pathway in the
      proliferation of EGFR-overexpressing tumour cells, and indicate a potential use
      for ABIN gene therapy in the treatment of cancer.

PMID- 18622429
TI  - Cobalt-catalyzed cross-coupling reactions.
AB  - In the last few years, we and other groups have demonstrated that economical
      cobalt salts can advantageously replace expensive and toxic catalysts for cross
      coupling reactions. These cobalt-catalyzed reactions have considerably extended
      the range of functionalized compounds. A variety of sensitive functional groups
      can be tolerated in these coupling reactions and various organic compounds RX
      could be involved (R = alkyl, alkynyl, aryl, allyl and X = halides: F, Cl, Br, I
      and even triflates). Here, we describe our contributions in this area for the
      preparation of a broad range of functionalized compounds from organometallic
      species or by direct cross-coupling.

PMID- 18622430
TI  - Nickel-catalysed reactions with trialkylboranes and silacyclobutanes.
AB  - Nickel catalysis enables us to develop new reactions with trialkylboranes and
      silacyclobutanes of modest reactivity. A combination of Ni(cod)(2) and tri-tert
      butylphosphine catalyses alkylation reactions of aldehydes and alpha,beta
      unsaturated esters with various trialkylboranes of modest reactivity, suppressing
      conceivable beta-hydride elimination from alkylnickel intermediates. A nickel
      catalyst is also useful for 1,4-addition of bis(pinacolato)diboron to alpha,beta
      unsaturated esters and amides. Nickel-catalysed reaction of silacyclobutanes with
      aldehydes results in ring opening to afford the corresponding alkoxyallylsilanes.
      In contrast, the ring expansion reaction of benzosilacyclobutene with aldehydes
      yields benzoxasilacyclohexenes. A nickel catalyst prepared from Ni(cod)(2) and
      tricyclohexylphosphine realises direct silylation of terminal alkenes with
      silacyclobutane furnishing vinylsilanes.

PMID- 18622431
TI  - An N-substituted aza[14]metacyclophane tetracation: a spin-quintet tetraradical
      with four para-phenylenediamine-based semi-quinone moieties.
AB  - A fully dianisylaminophenylated aza[1(4)]metacyclophane has been synthesized that
      exhibits four reversible two-electron oxidation processes, and its dicationic and
      tetracationic species have been found to be in spin-triplet and spin-quintet
      states.

PMID- 18622432
TI  - Reversible siRNA-polymer conjugates by RAFT polymerization.
AB  - A straightforward synthetic method to prepare pyridyl disulfide end
      functionalized poly(PEG acrylate) by RAFT polymerization for efficient and
      reversible conjugation to siRNA is described.

PMID- 18622433
TI  - Novel DOTA-based prochelator for divalent peptide vectorization: synthesis of
      dimeric bombesin analogues for multimodality tumor imaging and therapy.
AB  - Dimeric peptidic vectors, obtained by the divalent grafting of bombesin analogues
      on a newly synthesized DOTA-based prochelator, showed improved qualities as tumor
      targeted imaging probes in comparison to their monomeric analogues.

PMID- 18622434
TI  - Unexpected effect of the fluorine atom on the optimal ligand-to-palladium ratio
      in the enantioselective Pd-catalyzed allylation reaction of fluorinated enol
      carbonates.
AB  - The enantioselective Pd-catalyzed allylation reaction of fluorinated allyl enol
      carbonates is presented; a key feature of this transformation is the important
      effect of the ligand-to-palladium ratio on the enantioselectivity of the alpha
      fluoroketones, since using a ligand excess (L/Pd ratio = 1.25 : 1) led to
      moderate results (30-76% ee), while using a L/Pd ratio <1 : 1.67 (to as low as 1
      : 4) allowed the desired products to be obtained with high enantiopurity (up to
      94% ee).

PMID- 18622435
TI  - Conformational control in the regioselective synthesis of N-2-substituted-1,2,3
      triazoles.
AB  - An effective strategy for the synthesis of N-2-substituted-1,2,3-triazoles with
      excellent yields and regioselectivity has been developed.

PMID- 18622436
TI  - Renewable highest capacity VB2/air energy storage.
AB  - The first renewable electrochemical energy system which stores more energy than
      gasoline is presented, and with an order of magnitude higher capacity than
      lithium-ion batteries, VB(2) opens a pathway towards electric vehicles with a
      viable driving range.

PMID- 18622437
TI  - CO2 enhanced carbon nanotube synthesis from pyrolysis of hydrocarbons.
AB  - We report on the role of CO(2) in improving carbon nanotube yield and
      crystallinity from catalytic chemical vapor deposition of hydrocarbons.

PMID- 18622438
TI  - Blue phosphorescent emitters: new N-heterocyclic platinum(II) tetracarbene
      complexes.
AB  - Photoluminescence measurements show that platinum(II) tetracarbene complexes,
      which could be obtained via different synthetic routes, are interesting lead
      structures for the development of blue emitters for PhOLEDs with good quantum
      yields and high photostability.

PMID- 18622439
TI  - Anion dependant self-assembly and the first X-ray structure of a neutral
      homoleptic lanthanide salen complex Tb4(salen)6.
AB  - Reaction of H(2)salen (H(2)L) with Tb(OAc)(3).4H(2)O (3 : 2) in MeOH-MeCN under
      reflux gave homoleptic Tb(4)L(6) (1) in 40% yield; in contrast, similar reactions
      of Tb(NO(3))(3).6H(2)O and LnCl(3).6H(2)O (Ln = Tb, Nd and Yb) gave
      [TbL(NO(3))(MeOH)](2)(micro-H(2)L) (2) and [LnL(Cl)(MeOH)](2)(micro-H(2)L) (Ln =
      Tb (3), Nd (4) and Yb (5); H(2)L = N,N'-ethylenebis(salicylideneimine)).

PMID- 18622440
TI  - Cerium(IV)-containing oxomolybdenum cluster with a unique Ce6Mo9O38 core
      structure.
AB  - Interaction of [Ce(L(OEt))(2)(NO(3))(2)] (L(OEt)(-) = [Co(eta(5)
      C(5)H(5)){P(O)(OEt)(2)}(3)](-)) with (NH(4))(6)[Mo(7)O(24)] in water affords the
      cerium(iv)-containing oxomolybdenum cluster [H(4)(CeL(OEt))(6)Mo(9)O(38)], which
      exhibits a unique Ce(6)Mo(9)O(38) core structure.

PMID- 18622441
TI  - Propane reacts with O2 and H2 on gold supported TS-1 to form oxygenates with high
      selectivity.
AB  - Gold nanoparticles supported on a microporous titanosilicate (TS-1) were found to
      be highly selective (95%) towards the formation of acetone and isopropanol from
      propane, O(2), and H(2) at moderate temperatures (443 K).

PMID- 18622442
TI  - Structural changes in nanoporous solids due to fluid adsorption: thermodynamic
      analysis and Monte Carlo simulations.
AB  - A thermodynamic analysis based on the osmotic ensemble scheme enables the
      prediction of structural changes occurring in silicalite-1 zeolite upon
      halocarbon molecule adsorption.

PMID- 18622443
TI  - Self-association of the N-methyl benzotellurodiazolylium cation: implications for
      the generation of super-heavy atom radicals.
AB  - The N-methyl benzotellurodiazolylium cation self-associates in the solid state
      via short (2.471(3) A) 4-center TeN' intermolecular contacts; electrochemical
      data and the results of DFT calculations suggest that the dimers persist in
      solution.

PMID- 18622444
TI  - Photocyclization reaction of a diarylmaleimide derivative in polar solvents.
AB  - Photochromism of a symmetric diarylmaleimide derivative, having two thiophene
      rings (1), and a non-symmetric derivative having a S,S-dioxide thiophene ring and
      a thiophene ring (2) as the aryl moieties, was studied in various solvents. The
      photocyclization quantum yield of gradually decreased with increasing the solvent
      polarity and the reaction was not observed in polar solvents, such as ethanol and
      acetonitrile; on the other hand, such a strong solvent dependence of the
      photocyclization reaction was not observed for ; the different behavior is
      attributed to the weaker electron donating ability of the S,S-dioxide thiophene
      ring.

PMID- 18622445
TI  - Facile unidirectional alignment of mesochannels in a mesoporous silica film on a
      freshly cleaved mica surface.
AB  - The alignment of mesochannels in a mesoporous silica film on a freshly cleaved
      mica surface, prepared by an evaporation-induced self-assembly process, is
      unexpectedly found to be unidirectional with the narrowest directional
      distribution.

PMID- 18622446
TI  - Ortho-lithiation of free ferrocenyl alcohols: a new method for the synthesis of
      planar chiral ferrocene derivatives.
AB  - An ortho-metalation method for free ferrocenyl alcohols has been developed, which
      allows preparation of planar chiral ferrocene derivatives with high yields and
      diastereoselectivities.

PMID- 18622447
TI  - Ag microparticles embedded in Si nanowire arrays: a novel catalyst for gas-phase
      oxidation of high alcohol to aldehyde.
AB  - A novel catalyst of silver microparticles embedded in a silicon nanowire array
      support (Ag@SiNW) was prepared by an in situ electroless metal deposition method;
      it exhibited high selectivity and stability for gas-phase oxidation of high
      alcohol to its corresponding aldehyde.

PMID- 18622448
TI  - Preparation of self-supporting hierarchical nanostructured anatase/rutile
      composite TiO(2) film.
AB  - Via the combination of an electrospinning method with a hydrothermal reaction, a
      large-scale cedar-like hierarchical nanostructured TiO(2) film with an
      anatase/rutile composite phase was fabricated.

PMID- 18622449
TI  - A new and specific mode of stabilization of metallic nanoparticles.
AB  - We report in this paper the stabilization of ruthenium nanoparticles using a very
      simple ligand (4-(3-phenylpropyl)pyridine), through strong pi-coordination of the
      phenyl moiety.

PMID- 18622450
TI  - A multi-stage growth model leading to high-yield production of carbon nanotubes.
AB  - A novel growth model leading to high-yield production of carbon nanotubes with
      crystallized Ni(x)Mg(1-x)MoO(4) as the catalyst is revealed.

PMID- 18622451
TI  - Asymmetric multifunctional organocatalytic Michael addition of nitroalkanes to
      alpha,beta-unsaturated ketones.
AB  - Cinchona alkaloid derived primary amine thioureas organocatalyzed Michael
      addition of nitroalkanes to enones in good yield and up to 98% ee and offered a
      new way to construct quaternary stereocenters from enones and nitroalkanes.

PMID- 18622452
TI  - Monovalent indium in a sulfur-rich coordination environment: synthesis, structure
      and reactivity of tris(2-mercapto-1-tert-butylimidazolyl)hydroborato indium,
      [TmBut]In.
AB  - [Tm(Bu(t))]In, the first structurally-characterized monovalent indium compound
      that features a sulfur-rich coordination environment, has been synthesized via
      treatment of InCl with [Tm(Bu(t))]K; in contrast to the thallium counterpart, the
      lone pair of [Tm(Bu(t))]In is a site of reactivity, thereby allowing formation of
      [Tm(Bu(t))]In-->B(C(6)F(5))(3) and [Tm(Bu(t))]In(kappa(2)-S(4)) upon treatment
      with B(C(6)F(5))(3) and S(8), respectively.

PMID- 18622453
TI  - Oxygen-assisted reduction of Au species on Au/SiO2 catalyst in room temperature
      CO oxidation.
AB  - An unexpected oxygen-assisted reduction of cationic Au species by CO was found on
      a Au/SiO(2) catalyst at room temperature and the produced metallic Au species
      plays an essential role in CO oxidation on Au/SiO(2).

PMID- 18622454
TI  - Synthesis of allyl selenides by palladium-catalyzed decarboxylative coupling.
AB  - This communication details the Pd-catalyzed decarboxylation of selenocarbonates;
      use of a chiral nonracemic catalyst affords enantioenriched allyl selenides which
      undergo stereospecific [2,3]-sigmatropic rearrangements to form enantioenriched
      allylic amines and chlorides.

PMID- 18622455
TI  - Influence of a diene impurity on the molecular structure of phosphate-containing
      polymers with medical applications.
AB  - We have demonstrated that the unacknowledged presence of almost 30% diene
      impurity in some commercial phosphate monomers had not only a significant effect
      on the molecular structure (topology) of a series of synthesized polymers but the
      instability of the ester functionalities during these polymerizations resulted in
      unexpectedly complex co-polymer chemistry.

PMID- 18622456
TI  - Me2Zn mediated, tert-butylhydroperoxide promoted, catalytic enantioselective
      Reformatsky reaction with aldehydes.
AB  - A practical and highly enantioselective catalytic Reformatsky reaction with
      aldehydes using a cheap, commercially available aminoalcohol as ligand is
      described.

PMID- 18622457
TI  - [Mental health and continuity of care in healthcare centers in a city of
      Southeastern Brazil].
AB  - OBJECTIVE: To analyze factors associated with the continuity of mental health
      care provided for patients referred to healthcare centers. METHODS: A follow-up
      study was carried out with 98 patients assisted between 2003 and 2004. These
      patients were referred to eight healthcare centers with mental health teams
      located in the catchment area of a mental health reference venter in the city of
      Belo Horizonte, Southeastern Brazil. Social, demographic, clinical and continuity
      variables were described and then compared using the chi-square test. RESULTS:
      After referral, 35 patients did not attend the first visit in the healthcare
      center. Of those who did, 38 continued in treatment. To return to the reference
      center for a new visit after referral and to have had more than two referrals
      were factors that facilitated continuity of care. No individual characteristic
      was associated with continuity. CONCLUSIONS: The findings suggest that there is a
      gap in the proposal for the line of care. Treatment continuity seems to be more
      related to service factors than to patients' characteristics.

PMID- 18622458
TI  - [Health of families from the Landless Workers' Movement and temporary rural
      workers, Brazil, 2005].
AB  - OBJECTIVE: To assess the health conditions of families from the Landless Rural
      Workers' Movement and temporary rural workers. METHODS: The research involved a
      comparative study of three populations: a settlement and a camp linked to the
      Rural Workers' Movement, and the families of temporary rural workers in a city of
      Southeast Brazil, in 2005. Information relating to sociodemographic
      characteristics and families were collected by means of questionnaires that were
      put to 202 families. In addition, structured observation and group discussions
      were used. A discriminative factor analysis was carried out to confirm
      differences between the communities. RESULTS: The three communities scored an
      average of 89%, which implies that they are distinct groups and supports the
      hypothesis that there are real differences between them when it come to health
      and lifestyle conditions. There was a high rate of food insecurity (39.5%) among
      temporary rural workers, almost double that of families who were camping and four
      times greater than those living on settlements. Temporary rural workers' salaries
      were low and fluctuate, meaning that they were more exposed to pesticides than
      the families living on settlements or in camps. A striking characteristic of
      families living on the settlement was that they all practiced animal rearing,
      unlike the families of temporary rural workers, practically none of whom were
      able to do so in the city. The perceptions of most families who were living on
      settlements or in camps were that the Brazilian Health System had not been
      meeting their health needs, mainly due to access difficulties. For this group,
      their needs are met only after making complaints to and putting pressure on
      governors. CONCLUSIONS: The view held by families from the Landless Rural
      Workers' Movement was that the fact that they belonged to the Movement and were
      better organized meant their health was better than that of temporary rural
      workers. The conservative modernization of rural Brazil has led to worse
      conditions for temporary rural workers, while Agrarian Reform has allowed for a
      better quality of life and improved health conditions among families, when
      compared in the areas under study.

PMID- 18622460
TI  - [Eosinophilic esophagitis: a new disorder that causes inflammation in the
      digestive tract].

PMID- 18622461
TI  - [Evaluation of hepatic resection for hepatocellular carcinoma on cirrhotic
      livers].
AB  - BACKGROUND: The hepatocellular carcinoma is a disorder that affects patients
      suffering from cirrhosis. Liver resection, orthotopic liver transplantation and
      percutaneous ablation are some forms of therapy currently used to provide a cure
      for this disease. AIM: To assess the results achieved through liver resection for
      the treatment of the hepatocellular carcinoma in patients with cirrhosis being
      under treatment in a general hospital. METHODS: Clinical observation, laboratory
      test results, endoscopic and histopathologic analysis were taken into
      consideration in the case of 22 patients who underwent liver resection between
      1996 and 2005. To verify the survival rates, identify the prognostic factors and
      determine the risk of recurrence, special attention was given to the serologic
      levels of bilirubins and alpha-fetoprotein, and to the level of the
      hepatocellular dysfunction (classified according to the Child-Pugh-Turcotte and
      the Model for End-Stage Liver Disease parameters). The size and number of
      tumours, microvascular invasion and the presence of satellite lesions were also
      taken into consideration. The level of statistic significance employed was of
      95%. RESULTS: In the cases studied, patients had an average age of 62.09 years,
      being 17 of them male. In 10 cases the liver cirrhosis was associated to the
      hepatitis C chronic infection; in 4 cases there was a combination of chronic
      ingestion of ethanol and the hepatitis C virus; in 3 cases there was an
      association with the hepatitis B virus chronic infection. Two cases were related
      to the chronic ingestion of ethanol alone and in one case the use of medications
      was reported. It was not possible to establish the etiology in two of the cases
      studied. Eighteen patients had a single tumour, 11 of them smaller than 5 cm. The
      survival rate varied between 10 days and 120 months, being of 33.5 months on
      average. At the end of the 1st, 3rd and 5th year, the survival rates were 61.90%,
      16.67% and 11.11%, respectively. Three patients died within the first 3 months
      after the liver resection. Thirteen patients died after the first 3 months, 12 of
      the cases associated to tumour recurrence and tumour progression. There was one
      death in the immediate post-operative period of a second operation carried out to
      remove a recurrent tumour. When it comes to the survival rate and the
      identification of prognostic factors, a relationship between patients survival
      and microvascular invasion was observed. No statically significant relationship
      was established between the survival rate and the serologic levels of bilirubins
      and alpha-fetoprotein or the level of hepatocellular dysfunction, size or number
      of tumours. However, a more significant incidence of tumour recurrence was
      observed in patients with microvascular invasion in the histopathologic study.
      CONCLUSION: In spite of the reduced number of cases studied, the surgical
      treatment of the hepatocellular carcinoma produced bad results. A careful
      selection of cases where surgery could be an option may be a decisive factor to
      improve such results. A careful selection of cases might be a decisive factor in
      order to improve such results.

PMID- 18622462
TI  - [Short-term and long-term postoperative complications after ileal pouch-anal
      anastomosis in familial adenomatous polyposis].
AB  - BACKGROUND: Restorative proctocolectomy is the procedure of choice to treat
      familial adenomatous polyposis, however it can be associated to short-term and
      long-term postoperative complications. AIM: To evaluate the occurrence of
      complications related to the surgical treatment of familial adenomatous polyposis
      with ileal pouch technique. METHODS: Retrospective study of 69 patients with
      familial adenomatous polyposis after rectocolectomy with ileal reservoir between
      1984 and 2006, operated on Coloproctology Group, Medical Sciences Faculty, State
      University of Campinas, Campinas, SP, Brazil. The median follow-up period was 82
      (2-280) months. Data obtained were surgical techniques and postoperative
      complications. RESULTS: The morbidity and mortality were 63.8% and 2.9%,
      respectively. The most frequent complications were small-bowel obstruction
      (17.4%), anastomotic stricture (15.9%) and pelvic sepsis (10.1%). Acute ischemia
      of the ileal pouch (4.3%), pouchitis (2.9%) and ileal pouch-related fistula
      (2.9%) had poorer frequency than others. CONCLUSIONS: The morbid-mortality was
      similar to the literatures data and it is acceptable for a complex surgery in two
      terms like the ileal reservoir-anal anastomosis. The small-bowel obstruction was
      the most frequent complication. However, ischemia of the reservoir, pouchitis and
      pelvic sepsis were important complications and was related to the failure of the
      ileal reservoir.

PMID- 18622463
TI  - [Weight, educational achievement, basic sanitation, alcoholism, smoking and
      eating habit in patients with gastric cancer].
AB  - BACKGROUND: About 35% of the cancer patients are involved in factors coming from
      the diet and others like alcohol, smoking, sunlight, chemical agents and
      infections caused by virus. The stomach cancer is the second cause of cancer in
      the world with 9.9 % of all diagnosis and about 12.1 % of death cases. AIMS:
      Evaluate the body weight, educational achievement, basic sanitation, smoking,
      alcoholism and eating habit among patients with gastric cancer and a control
      group. METHODS: Seventy patients with gastric cancer were paired with 70 subjects
      without cancer. Data on the weight and height, educational attainment, basic
      sanitation, smoking, alcoholism and eating habits of the patients were collected
      from the clinical records and from interviews. RESULTS: Forty two patients were
      men, the mean age were 60 years old. The actual weight and body mass index of the
      patients were smaller when compared to the controls. Within the group of patients
      with gastric cancer, 21 never attended school, and for those who attended, 55%
      did not finish the elementary school. Among the patient group, 32.9% of them
      lived in housing with basic sanitation and 37.1% with electricity, against 68.6%
      of the controls, and 58.6% of the patients lived in rural area, against only 7.1%
      of the controls. Among the test group, 65.7% of the patients were smokers,
      whereas in the control group, 44.3% were smokers. In addition, there was also
      difference in the duration of smoking habit. Alcoholism was also more frequent in
      the cancer group (44% vs 19%). Food rich in salt, condiments, nitrates, saturated
      fat, complex carbohydrates, refined sugar and fried salted food had been more
      used by gastric cancer patients. CONCLUSION: The patients with gastric cancer
      presented with: less weight, low quality of life as indicated by lower or no
      access to basic sanitation, electricity and schooling, lived predominantly in
      rural area, high incidence of alcohol intake and higher intake of high fat foods
      and industrialized foods.

PMID- 18622464
TI  - [Nosocomial diarrhea in the intensive care unit: incidence and risk factors].
AB  - BACKGROUND: Nosocomial diarrhea seems to be common at intensive care units,
      although its epidemiology be poorly documented in Brazil. AIM: To determine the
      incidence and risk factors of diarrhea among adult patients admitted to intensive
      care units. METHODS: Four hundred and fifty five patients were prospectively
      included during the period between October 2005 and October 2006. Demographic,
      clinical and biochemical data as well as aspect and number of bowel movements
      were recorded on a daily basis until discharge from the unit. RESULTS: Diarrhea
      occurred in 135 (29.5%) patients, lasting 5.4 days average. The time of its onset
      in according to admission was 17.8 days and similar cases of diarrhea during the
      same period were recorded in 113 (83.7%) patients. In a multivariate analysis
      through the logistics regression model, only the number of antibiotics (OR 1.65;
      I.C. 95% = 1.39-1.95) and the number of days of antibiotic therapy (OR 1.16; I.C.
      95% = 1.12-1.20) were statistically associated with the diarrhea occurrence. Each
      day added of antibiotic therapy, raised in 16% the risk of diarrhea (I.C. 12% to
      20%), while the addition of one more antibiotic to the scheme, increased the
      chances of occurring diarrhea in 65% (I.C. 39% to 95%). CONCLUSION: The incidence
      of nosocomial diarrhea in intensive care units is high (29.5%). The main risk
      factors for its occurrence were number of prescribed antibiotics and duration of
      the antibiotic therapy. Besides the enteric precautions, judicious and limited
      prescription of antimicrobians probably will reduce the occurrence of diarrhea at
      this unit.

PMID- 18622465
TI  - Consumption of red-hot chili pepper increases symptoms in patients with acute
      anal fissures. A prospective, randomized, placebo-controlled, double blind,
      crossover trial.
AB  - BACKGROUND: Red-hot chili pepper and other spices have been blamed for causing or
      exacerbating symptoms of anal pathologies like anal fissure and hemorrhoids. AIM:
      To determine if consumption of chilies increases symptoms of acute anal fissures.
      METHODS: Individual patients were randomized to receive capsules containing chili
      or placebo for one week in addition to analgesics and fiber supplement. Patients
      were asked to note score for symptoms like pain, anal burning, and pruritus
      during the study period. After 1 week, cross over treatment was administered to
      the same group of patients with the same methodology and results were noted at
      the end of 2 weeks. RESULTS: Fifty subjects were recruited for this study. Forty
      three of them completed the trial (22 in the chili group and 21 in the placebo
      group). The daily mean pain score was significantly lower in the placebo group in
      the study period. Score 2.05 in chili group and 0.97 in placebo group. There was
      a significant burning sensation experienced by the patients in the chili group
      (score 1.85 for the chili group vs 0.71 for the placebo group). Patients mean
      recorded improvement score was significantly higher after taking placebo. Eighty
      one point three percent patients preferred placebo while 13.9% preferred chilies.
      Two patients had no preference. CONCLUSION: Consumption of chili does increase
      the symptoms of acute anal fissure and reduces patient compliance.

PMID- 18622466
TI  - Prevalence of rectoanal inhibitory reflex in chagasic megacolon.
AB  - BACKGROUND: Rectoanal inhibitory reflex is not always evident in patients with
      chagasic megacolon. This may be due to insufficient volumes of air used during
      insufflation for the manometric examination. AIMS: To identify the volume of air
      necessary to induce rectoanal inhibitory reflex in patients with chagasic
      megacolon and to observe its prevalence in these individuals. METHODS: Rectoanal
      inhibitory reflex in 39 patient with chagasic megacolon was studied by means of
      anorectal manometry using the balloon method. The balloon was insufflated using
      sequential volumes up to 300 mL to induce reflex. RESULTS: Rectoanal inhibitory
      reflex was identified in 43.6% of the patients using a mean volume of 196 mL of
      insufflated air (standard error = 13.5). CONCLUSION: Rectoanal inhibitory reflex
      can be induced in patients with chagasic megacolon when greater volumes of air
      are used.

PMID- 18622467
TI  - [Study in oral cavity alterations in patients with gastroesophageal reflux
      disease].
AB  - BACKGROUND: The gastroesophageal reflux disease, which has become highly and
      increasingly incident, may be manifested by typical (pyrosis and regurgitation)
      and atypical (pulmonary, otorhinolaryngological and buccal) symptoms. AIM: To
      analyze alterations in the oral cavity patients with gastroesophageal reflux
      disease. METHODS: One hundred patients were studied being 50 gastroesophageal
      reflux disease patients (group 1) and 50 controls (group 2). All patients were
      submitted to an oral clinical exam and specific survey. Patients in group 1 were
      submitted to upper endoscopy, manometry and esophageal pH monitoring. RESULTS:
      The upper endoscopy revealed esophagitis in all patients, 20 erosive esophagitis,
      30 no-erosive esophagitis and 38 hiatal hernia. Average pressure of the lower
      esophageal sphincter was 11 +/- 4,8 mm Hg and of the upper esophageal sphincter
      75 +/- 26,5 mm Hg. In 42 patients of group 1 (84%) pathological gastroesophageal
      reflux was observed. Clinical exams revealed: dental erosions in group 1: 273
      faces and in group 2: 5 tooth decays in group 1: 23 and 115 in group 2; abrasion
      in group 1: 58 and in group 2: 95; attrition wear: 408 in group 1 and 224 in
      group 2. The most damages was the palatine face. In group 1, 21 patients
      complained about frequent episodes of canker sores, 35 of tooth sensibility, 26
      of burning mouth and 42 of sour taste in the mouth. In group 2 the complaints
      were observed in lower number of patients. CONCLUSIONS: Patients with
      gastroesophageal reflux disease present higher incidence of dental erosion,
      canker sores, mouth burning sensation, sensitivity and sour taste than controls.
      Patients with gastroesophageal reflux disease show lower incidence of tooth
      decays as compared to controls.

PMID- 18622468
TI  - Seroprevalence and risk factors for hepatitis B virus infection among general
      population in Northern India.
AB  - BACKGROUND: Infection with hepatitis-B virus has been a significant cause of
      morbidity claiming more than a million lives every year. Epidemiological data
      reveals that there are 360 million carriers of hepatitis-B virus throughout the
      globe and 78% of the world populations' hail from Asia. Though several studies
      from Indian sub-continent have provided an estimate of the prevalence of this
      viral infection, there exist only few studies, which reflect the status in the
      general population. AIM: The present study was designed to investigate the
      prevalence of hepatitis-B infection in North Indian general population. METHODS:
      The study population comprised of 20,000 healthy blood donors who were screened
      for hepatitis-B surface antigen (HBsAg) status using third generation ELISA kit.
      Seroprevalence rate of seropositive donors was calculated and stratified by age,
      sex and blood groups. Statistical analysis was performed using tests of
      proportions, chi-square and confidence interval. RESULTS: The study showed that
      out of 20,000 donors, 450 (2.25%) were HBsAg positive (95% confidence interval
      (CI), 2.0445-2.4554). Higher prevalence of HbsAg was found among males
      (440/19235) than females (10/765). The age specific prevalence rose from 1.78%
      (108/6058) in donors aged 19-25 years to a maximum of 3.03% (96/3161) in donors
      aged 35-45 years and decreased in older age groups. The peaks were detected in
      male donors aged 35-45 years and in females aged 25-35 years. Rh-negative blood
      group donors (21/873) and Rh-positive group donors (429/19127) had almost
      equivalent prevalence rates of HBsAg. HBsAg was more prevalent in blood group B
      donors (174/7426) and less prevalent in AB blood group donors (38/2032).
      CONCLUSION: It was found that variables including gender and age were
      significantly associated with HBsAg positivity. HBsAg positivity in our
      population was statistically not associated with ABO blood groups.

PMID- 18622469
TI  - [Eosinophilic esophagitis in 29 pediatric patients].
AB  - BACKGROUND: Eosinophilic esophagitis is a recently described entity with
      esophageal symptoms like gastroesophageal reflux disease and significant
      esophageal eosinophilic infiltration. AIM: To present our clinical series of 29
      children with eosinophilic esophagitis, describing the clinical and diagnostic
      features, treatment and outcome. METHODS: We describe 29 patients (22 boys), 1-18
      years-old, with 20 eosinophils per high-power field in esophageal biopsy
      specimens and absence of eosinophilic inflammation in the stomach and duodenum.
      Evaluation of the clinical, endoscopic and histologic findings, treatment and
      outcome was undertaken. RESULTS: The most common presenting symptoms included
      vomiting in 15 patients (52%) and abdominal pain in 11 patients (38%). Children
      under the age of 4 years presented with feeding disorder and failure to thrive.
      Patients between 5 and 8 years of age presented commonly with abdominal pain or
      symptoms that may be associated with reflux (heartburn and/or vomiting). Patients
      over the age of 8 presented most often with abdominal pain, dysphagia and
      occasional food impaction. Endoscopic features included vertical furrowing in 14
      patients (48%), whitish papules in 12 (41%), corrugated rings in 2 patients (7%)
      and esophageal erosions in 3 patients (10%). In seven patients endoscopy was
      normal (24%). Treatment included swallowed fluticasone propionate in 19 patients
      and restriction diet in 7 patients. Patients who returned for follow-up had
      either improvement or remission of symptoms. After treatment, endoscopic biopsies
      were repeated in 11 patients, and a significant decrease in esophageal eosinophil
      counts was observed. CONCLUSIONS: The diagnosis of eosinophilic esophagitis must
      be considered when symptoms of reflux do not respond to conventional treatment.
      Upper gastrointestinal endoscopy must be complemented by a detailed analysis of
      histologic findings and eosinophil counts.

PMID- 18622470
TI  - Decrease in prevalence of Helicobacter pylori infection during a 10-year period
      in Brazilian children.
AB  - BACKGROUND: Decreasing prevalence of H pylori infection has been reported in some
      countries. AIM: To evaluate the prevalence of Helicobacter pylori infection in a
      10-year period in children submitted to upper digestive endoscopy. METHODS: It
      was a retrospective observational study. The records of 1,165 endoscopies
      performed during a 10-year period in a public hospital of the City of Sao Paulo,
      SP, Brazil, in patients up to 18-year-old. Only the first endoscopy was
      considered. Helicobacter pylori infection was defined by the rapid urease test,
      performed with one fragment of antral mucosa. Chi-square for trend has been
      estimated to compare Helicobacter pylori prevalence across the period. RESULTS:
      The main indication for endoscopy was epigastric pain (47.4%). There were 392
      patients with H pylori infection (33.6%), 12.8% being infants, 19.4% toddlers,
      28.8% schoolchildren and 46.3% adolescents. Prevalence was 60.47% in the first
      year of the study and 30.43% in the last. Among the less than 6-year-old patients
      there was a decrease in infection prevalence from 25% for the 1993--6 period to
      14.3% in the 2000--02 period, while among the over 12-year-old patients the
      decrease was from 55.5% in the first period to 39.6% in the latter. The decrease
      in H pylori infection prevalence was more intense within patients with epigastric
      pain, in which prevalence has decreased from 48.2% (92/191) in 1993--6, to 41.9%
      (65/155) in 1997--9 and 27.7% (57/206) in 2000--02. CONCLUSION: The study
      suggests a significant decrease in the prevalence of H pylori infection regarding
      the studied patients. The trend was mainly observed in the younger age group and
      in patients with epigastric pain.

PMID- 18622471
TI  - Clinical and laboratory evaluation of 101 patients with intrahepatic neonatal
      cholestasis.
AB  - BACKGROUND: Intrahepatic neonatal cholestasis can be the initial manifestation of
      a very heterogeneous group of illnesses of different etiologies. AIM: To evaluate
      and compare clinical and laboratory data among intrahepatic neonatal cholestasis
      groups of infectious, genetic-endocrine-metabolic and idiopathic etiologies.
      METHODS: The study evaluated retrospectively clinical and laboratory data of 101
      infants, from March 1982 to December 2005, 84 from the State University of
      Campinas Teaching Hospital, Campinas, SP, Brazil, and 17 from the Child's
      Institute of the University of Sao Paulo, SP, Brazil. The inclusion criteria
      consisted of: jaundice beginning at up to 3 months of age and hepatic biopsy
      during the 1st year of life. It had been evaluated: clinical findings (gender,
      age, birth weight, weight during the first medical visit, stature at birth,
      jaundice, acholia/hipocholia, choluria, hepatomegaly and splenomegaly) and
      laboratorial (ALT, AST, FA, GGT, INR). RESULTS: According to diagnosis, patients
      were classified into three groups: group 1 (infectious) n = 24, group 2 (genetic
      endocrine-metabolic) n = 21 and group 3 (idiopathic) n = 56. There were no
      significant differences in relation to the variables: age, gender, stature at
      birth, jaundice, acholia/hipocholia, choluria, hepatomegaly, splenomegaly, AST,
      ALT, ALP, GGT, DB and albumin. Significant differences were observed in relation
      to the following variables: birth weight and weight during the first medical
      visit. Birth weight of group 1 was lower in relation group 2 and 3. Weight during
      the first medical visit followed the same pattern. There was a statistically
      significant difference in relation to the INR, as the patients of the group 2
      presented higher values in relation to groups 2 and 3, despite the median was
      still pointing out normal values. CONCLUSIONS: There were no significant
      differences in relation to age, gender, stature at birth, jaundice,
      acholia/hipocholia, choluria, hepatomegaly, splenomegaly, AST, ALT, ALP, GGT, BD
      and albumin. Birth weight and the weight during the first medical visit were
      lower in the group with infectious etiology. In addition, a significant
      difference in INR reflected impaired coagulation of patients of the group of the
      genetic-endocrine-metabolic disease.

PMID- 18622472
TI  - Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats.
AB  - BACKGROUND: Hepatic cirrhosis is the final stage of liver dysfunction,
      characterized by diffuse fibrosis which is the main response to the liver injury.
      The inhalatory carbon tetrachloride is an effective experimental model that
      triggers cirrhosis and allows to obtain histological and physiological
      modifications similar to the one seen in humans. AIM: To investigate the effects
      of N-acetylcysteine (NAC) on the fibrosis and oxidative stress in the liver of
      cirrhotic rats, analyzing liver function tests, lipoperoxidation, activity of
      glutathione peroxidase enzyme, collagen quantification, histopathology, as well
      as the nitric oxide role. METHODS: The animals were randomly in three
      experimental groups: control (CO); cirrhotic (CCl4) and CCl4 + NAC. Evaluate the
      lipid peroxidation, the glutathione peroxidase enzyme, the collagen and the
      expression of inducible nitric oxide synthase (iNOS). RESULTS: The cirrhotic
      group treated with N-acetylcysteine showed trough the histological analysis and
      collagen quantification lower degrees of fibrosis. This group has also shown less
      damage to the cellular membranes, less decrease on the glutathione peroxidase
      levels and less expression of inducible nitric oxide synthase when matched with
      the cirrhotic group without treatment. CONCLUSION: N-acetylcysteine seams to
      offer protection against hepatic fibrosis and oxidative stress in cirrhotic rat
      livers.

PMID- 18622473
TI  - [Epiploic appendagitis: clinical and radiological aspects].
AB  - Epiploic appendagitis is an uncommon inflammatory abdominal disease. Data of 44
      patients with a clinical diagnosis of appendagitis were retrospectively evaluated
      regarding laboratory and imaging findings. They were admitted to Barra D'Or
      Hospital, Rio de Janeiro, RJ, from February 2005 to September 2006. Eighty-two
      percent were male and 18 were female, with median age of 44.7 years. The most
      frequent laboratory findings were hematuria in urinalysis and leucocitosis,
      presenting in 5% of cases each. Diagnosis was obtained through computed
      tomography showing paracolic oval lesions, mainly over the descending colon in
      52% of patients. Patients were treated with analgesics and anti-inflammatory in
      an outpatient basis. Recovery was uneventful under conservative treatment.

PMID- 18622474
TI  - [Parasitic infection of the appendix and its possible relationship to acute
      appendicitis].
AB  - From 1,600 surgically removed appendices, 24 (1.5%) were found to have helminths.
      Enterobius vermicularis was observed in 23 of the 24 specimens (95.8%) and Taenia
      sp was detected in only 1 (4.2%) case. Sixteen patients (66.7%) were less than 10
      year-old; 15 patients were male and 9 female. Pathologic analysis disclosed acute
      neutrophilic inflammation in 12 cases and lymphoid hyperplasia in 10 of the 24
      appendices. Gangrenous appendicitis was diagnosed in 3 cases and peritonitis was
      found in 11 of the 24 infested appendices. Parasitic infection of the appendix is
      an uncommon cause of acute appendicitis in children and adolescents.

PMID- 18622476
TI  - Clinical trial registration--now required.

PMID- 18622475
TI  - [Early pancreatic cancer: can the methods currently available identify this
      disease?].
AB  - OBJECTIVES: Call attention of the gastroenterologists and surgeons on the
      patients with high risk of developing pancreatic carcinoma, and whether or not
      forms of surveillance and prevention of this disease, which can be applied to
      daily clinical practice. DATA SURVEY: It was used the database of PubMed (US
      National Library of Medicine), looked up the publications of recent years for the
      groups at risk, molecular biological testing and methods of image used in the
      identification of small tumors of the pancreas. BACKGROUND: The survival rates of
      adenocarcinoma of the pancreas remain negligible, even after the significant
      advances in diagnosis by imaging, treatment and understanding of the molecular
      biology of this disease. Although embryonic strategies for surveillance and
      prevention for people with high risk of pancreatic cancer has developed.
      CONCLUSIONS: This review summarizes how to identify people at high risk of
      developing this disease and what is the state of the art of genetic counseling
      and screening through techniques of image available.

PMID- 18622477
TI  - Anatomic variation of cranial parasympathetic ganglia.
AB  - Having broad knowledge of anatomy is essential for practicing dentistry. Certain
      anatomical structures call for detailed studies due to their anatomical and
      functional importance. Nevertheless, some structures are difficult to visualize
      and identify due to their small volume and complicated access. Such is the case
      of the parasympathetic ganglia located in the cranial part of the autonomic
      nervous system, which include: the ciliary ganglion (located deeply in the orbit,
      laterally to the optic nerve), the pterygopalatine ganglion (located in the
      pterygopalatine fossa), the submandibular ganglion (located laterally to the
      hyoglossus muscle, below the lingual nerve), and the otic ganglion (located
      medially to the mandibular nerve, right beneath the oval foramen). The aim of
      this study was to present these structures in dissected anatomic specimens and
      perform a comparative analysis regarding location and morphology. The proximity
      of the ganglia and associated nerves were also analyzed, as well as the number
      and volume of fibers connected to them. Human heads were dissected by planes,
      partially removing the adjacent structures to the point we could reach the
      parasympathetic ganglia. With this study, we concluded that there was no
      significant variation regarding the location of the studied ganglia.
      Morphologically, our observations concur with previous classical descriptions of
      the parasympathetic ganglia, but we observed variations regarding the proximity
      of the otic ganglion to the mandibular nerve. We also observed that there were
      variations regarding the number and volume of fiber bundles connected to the
      submandibular, otic, and pterygopalatine ganglia.

PMID- 18622478
TI  - In vitro assessment of the effectiveness of whitening dentifrices for the removal
      of extrinsic tooth stains.
AB  - This in vitro study evaluated the effectiveness of whitening dentifrices for the
      removal of extrinsic tooth stains. Twenty dental blocks (4 x 4 mm), including
      enamel and dentine, removed from freshly extracted bovine incisors, were randomly
      divided into 4 groups: G1--distilled water, G2--Colgate, G3--Crest Extra
      Whitening and G4--Rapid White. In all specimens, the dentin was covered with
      colorless nail polish, and the enamel was left exposed. Next, the specimens were
      immersed in a solution of black tea, which was changed every 24 h, for a period
      of 6 days. After this period, a photo-reflectance reading was taken (Time 1) with
      a spectrometer. The stained specimens were then submitted to linear brushing
      movements (5,000 cycles) using brushes (Oral B-Soft) coupled to an automatic
      toothbrushing machine, under a static axial load of 200 g and with a speed of 4
      movements/second, at 37 degrees C, with the dentifrice or water being injected
      every 60 s. When toothbrushing ended, a second photo-reflectance reading was
      taken (Time 2). The results were submitted to two-criteria analysis of variance
      (ANOVA) and to the Tukey test ( = 0.05). When the two times for a same group were
      compared, Time 2 presented the highest reflectance values with statistical
      difference only for G3 and G4. Among the dentifrices tested, only the Rapid White
      group differed from the control group, presenting the highest reflectance values.
      Only the whitening dentifrice Rapid White was effective for the removal of
      extrinsic stains.

PMID- 18622479
TI  - In vitro toothbrushing abrasion of dental resin composites: packable,
      microhybrid, nanohybrid and microfilled materials.
AB  - This study evaluated weight loss and surface roughening after toothbrushing of
      different resin composites: one packable (Solitaire 2, Heraeus Kulzer), one
      microhybrid (Charisma, Heraeus Kulzer), one nanohybrid (Simile, Pentron) and one
      microfilled (Durafill VS, Heraeus Kulzer). Cylindrical specimens (n = 20) were
      prepared. Half of the samples were submitted to 60,000 strokes, at 4 Hz, with a
      dentifrice-water slurry. Control samples (n = 10) remained stored at 37 degrees
      C. Pre- and post-abrasion parameters for weight (mg) and surface roughness (Ra,
      microm) were determined on an analytical balance and a surface profilometer. Data
      were separately submitted to Repeated Measures ANOVA and Tukey's test (a = 0.05).
      Percentages of weight loss were analyzed by ANOVA and Tukey's test (a = 0.05).
      The relationship between both evaluations was assessed by Pearson's test (a =
      0.05). The means (%) for weight loss (standard deviation) were 0.65(0.2),
      0.93(0.2), 1.25(0.6) and 1.25(0.4) for Simile, Durafill, Charisma and Solitaire,
      respectively. Baseline roughness means ranged from 0.065(0.01), 0.071(0.01),
      0.066(0.02) and 0.074(0.01) for Simile, Durafill, Charisma and Solitaire,
      respectively, to 0.105(0.04), 0.117(0.03), 0.161(0.03) and 0.214(0.07) after
      testing. The composites with larger fillers presented higher weight loss and
      roughening than the finer materials (p < 0.05). For both evaluations, control
      specimens showed no significant alteration. No significant relationship between
      loss of weight and roughness alteration was detected (r = 0.322, p = 0.429).

PMID- 18622480
TI  - Optimizing the procedure for mercury recovery from dental amalgam.
AB  - Mercury, as any other heavy metal, may cause environmental damages due to its
      accumulation and biotransformation. Dental offices, whether private or
      institutional, use dental amalgam as a restorative material on a daily basis.
      Dental amalgam is composed of mercury (50%), silver (30%) and other metals.
      Approximately 30% of the amalgam prepared in dental offices (0.6 g per capsule)
      are wasted and inadequately discarded without any treatment. Methods for mercury
      recovery have been proposed previously, using high temperatures through exposure
      to direct flame (650 degrees C), long processing time, and hazardous reagents as
      potassium cyanide. The purpose of this study was to develop a method to replace
      the direct flame by an electrical mantle in the process of mercury recovery.
      Results showed an average mercury recovery of 90% from 2 kg of amalgam after 30
      minutes of processing time, thus optimizing the procedure. The proposed
      modifications allowed a significant reduction in processing time and a mercury
      recovery with high purity. The modified process also provided minimization of
      operator exposure to physical, chemical and ergonomic hazards, representing a
      technological advance compared to the risks inherent to the original method. It
      also provided environmental health and economy of energy resources by replacing a
      finite energy source (fossil and organic) by a more environmentally appropriate
      electric source, resulting in significant improvement of the procedure for
      mercury recovery from dental amalgam.

PMID- 18622481
TI  - In vitro integrity of implant external hexagon after application of surgical
      placement torque simulating implant locking.
AB  - The aim of this study was to evaluate the integrity of the external hexagon of an
      implant system with internal and external hexagons but with prosthetic connection
      through the external hexagon (Internal Torque, IT) in comparison with that of an
      implant system with external hexagon with mount (External Hexagon, EH). A device
      was made to measure the rotational freedom angles between implant and abutment
      hexagons in 10 implants from each group after the application of surgical
      placement torques of 45, 60 and 80 Ncm simulating implant locking. The distances
      between the vertices of the external hexagon were also obtained. Rotational
      freedom data were subjected to ANOVA and Tukey's test (P < .05) showing no
      significant difference between the angles of the intact implants (EH - 3.31 +/-
      0.41 degrees and IT - 3.30 +/- 0.17 degrees ) and after application of a 45 Ncm
      torque (EH - 3.27 +/- 0.38 degrees and IT - 3.31 +/- 0.22 degrees ). However,
      after application of a 60 Ncm torque there were significant differences (IT -
      3.40 +/- 0.20 degrees and EH - 4.03 +/- 0.54 degrees ). After application of a 80
      Ncm torque, the IT implant presented values of 3.39 +/- 0.21 degrees whereas the
      EH did not support the torque, suffering deformation of its external hexagon.
      Within the limits of this study, it can be concluded that the IT implant system
      may be preferable in clinical situations where implant placement within a certain
      bone density could generate torques higher than 60 Ncm.

PMID- 18622482
TI  - Scanning electron microscopic study of the in situ effect of salivary stimulation
      on erosion and abrasion in human and bovine enamel.
AB  - This in situ study investigated, using scanning electron microscopy, the effect
      of stimulated saliva on the enamel surface of bovine and human substrates
      submitted to erosion followed by brushing abrasion immediately or after one hour.
      During 2 experimental 7-day crossover phases, 9 previously selected volunteers
      wore intraoral palatal devices, with 12 enamel specimens (6 human and 6 bovine).
      In the first phase, the volunteers immersed the device for 5 minutes in 150 ml of
      a cola drink, 4 times a day (8h00, 12h00, 16h00 and 20h00). Immediately after the
      immersions, no treatment was performed in 4 specimens (ERO), 4 other specimens
      were immediately brushed (0 min) using a fluoride dentifrice and the device was
      replaced into the mouth. After 60 min, the other 4 specimens were brushed. In the
      second phase, the procedures were repeated but, after the immersions, the
      volunteers stimulated the salivary flow rate by chewing a sugar-free gum for 30
      min. Enamel superficial alterations of all specimens were then evaluated using a
      scanning electron microscope. Enamel prism core dissolution was seen on the
      surfaces submitted to erosion, while on those submitted to erosion and to
      abrasion (both at 0 and 60 min) a more homogeneous enamel surface was observed,
      probably due to the removal of the altered superficial prism layer. For all the
      other variables--enamel substrate and salivary stimulation -, the microscopic
      pattern of the enamel specimens was similar.

PMID- 18622483
TI  - Comparative analysis of the effect of two chlorhexidine mouthrinses on plaque
      accumulation and gingival bleeding.
AB  - The aim of the present study was to evaluate the effect of two chlorhexidine
      rinsing solutions (0.12% and 0.2%) on plaque and gingival bleeding. Ten dental
      students participated in this double-blind, cross-over study, rinsing twice a
      day, for one minute, with each one of the tested solutions for fourteen days. A
      wash-out period of one week between treatments was observed. In order to assess
      gingival bleeding, the van der Weijden et al.(1) (1994) index was used. The
      plaque indexes used were those of Quigley, Hein(2) (1962) and Silness, Loe(3)
      (1964). In the pre-experimental period, subjects received oral hygiene
      instructions and dental prophylaxis. The results revealed no significant
      differences between both concentrations in relation to plaque and gingival
      bleeding. Mean values (+/- standard deviation) of the Quigley & Hein index were
      0.25 +/- 0.16 for the 0.12% solution and 0.23 +/- 0.26 for the 0.2% solution (p =
      0.4838). Mean values (+/- standard deviation) of the Silness-Loe index were 0.12
      +/- 0.10 for the 0.12% solution and 0.11 +/- 0.11 for the 0.2% solution (p =
      0.7592). The bleeding index mean values at the end of the study were not
      different for both concentrations with mean values (+/- standard deviation) of
      14.93% +/- 6.68% and 13.95 +/- 9.24% for the 0.12% and 0.2% solutions,
      respectively. Although an increase in gingival bleeding was observed, both
      concentrations were able to control dental plaque.

PMID- 18622484
TI  - Metronidazole-containing gel for the treatment of periodontitis: an in vivo
      evaluation.
AB  - The aim of this investigation was to monitor metronidazole concentrations in the
      gingival crevicular fluid (GCF) collected from periodontal pockets of dogs after
      treatment with an experimental 15% metronidazole gel. Five dogs had periodontitis
      induced by cotton ligatures placed subgingivally and maintained for a 30-day
      period. After the induction period, only pockets with 4 mm or deeper received the
      gel. Each pocket was filled up to the gingival margin by means of a syringe with
      a blunt-end needle. GCF was collected in paper strips and quantified in an
      electronic device before and after 15 minutes, 1 h, 6 h, 24 h and 48 h of gel
      administration. The GCF samples were assayed for metronidazole content by means
      of a high performance liquid chromatography method. Concentrations of
      metronidazole in the GCF of the 5 dogs (mean +/- SD, in microg/mL) were 0 +/- 0
      before gel application and 47,185.75 +/- 24,874.35 after 15 minutes, 26,457.34 +/
      25,516.91 after 1 h, 24.18 +/- 23.11 after 6 h, 3.78 +/- 3.45 after 24 h and
      3.34 +/- 5.54 after 48 h. A single administration of the 15% metronidazole gel
      released the drug in the GCF of dogs in levels several-fold higher than the
      minimum inhibitory concentration for some periodontopathogens grown in
      subgingival biofilms for up to one hour, but metronidazole could be detected in
      the GCF at least 48 hours after the gel application.

PMID- 18622485
TI  - Development of an experimental optoelectronic device to study the amplitude of
      mandibular movements.
AB  - This study aimed to present a wireless mandibular motion tracking device and
      optoelectronic data acquisition system developed to analyze the real-time spatial
      motion of the entire mandible during mouth opening and closing with no
      restriction of any movement. The procedures were divided into three phases:
      confection of a kinematic arch, dynamic digital video image acquisition, and
      image processing and analysis by using graphic computation. Four sequences of jaw
      opening/closing movements were recorded in lateral view: two from the maximum
      intercuspation (MIC) and the other two from a forced mandibular retruded
      position. Jaw motion was recorded by a digital video camera and processed as
      spatial coordinates corresponding to the position variation of the markers in the
      kinematic arch. The results showed that the method was capable of recording and
      processing the dynamics of the mandibular movements during jaw opening/closing
      using pixel-magnitude points. The mandible showed points with less displacement
      located near the temporomandibular joint during the opening/closing movements
      from the mandibular retruded position. When the jaw movements were recorded from
      MIC, these points were located near the mandibular foramen.

PMID- 18622486
TI  - Micro-morphological changes prior to adhesive bonding: high-alumina and glassy
      matrix ceramics.
AB  - The aim of this study was to qualitatively demonstrate surface micro
      morphological changes after the employment of different surface conditioning
      methods on high-alumina and glassy-matrix dental ceramics. Three disc-shaped high
      alumina specimens (In-Ceram Alumina, INC) and 4 glassy-matrix ceramic specimens
      (Vitadur Alpha, V) (diameter: 5 mm and height: 5 mm) were manufactured. INC
      specimens were submitted to 3 different surface conditioning methods: INC1-
      Polishing with silicon carbide papers (SiC); INC2--Chairside air-borne particle
      abrasion (50 microm Al2O3); INC3 - Chairside silica coating (CoJet; 30 microm
      SiOx). Vitadur Alpha (V) specimens were subjected to 4 different surface
      conditioning methods: V1--Polishing with SiC papers; V2 - HF acid etching; V3-
      Chairside air-borne particle abrasion (50 microm Al2O3); V4--Chairside silica
      coating (30 microm SiOx). Following completion of the surface conditioning
      methods, the specimens were analyzed using SEM. After polishing with SiC, the
      surfaces of V specimens remained relatively smooth while those of INC exhibited
      topographic irregularities. Chairside air-abrasion with either aluminum oxide or
      silica particles produced retentive patterns on both INC and V specimens, with
      smoother patterns observed after silica coating. V specimens etched with HF
      presented a highly porous surface. Chairside tribochemical silica coating
      resulted in smoother surfaces with particles embedded on the surface even after
      air-blasting. Surface conditioning using air-borne particle abrasion with either
      50 microm alumina or 30 microm silica particles exhibited qualitatively
      comparable rough surfaces for both INC and V. HF acid gel created the most micro
      retentive surface for the glassy-matrix ceramic tested.

PMID- 18622487
TI  - Influence of different light curing units on the bond strength of indirect resin
      composite restorations.
AB  - The aim of this study was to evaluate the influence of different light sources on
      the bond strength of indirect resin composite restorations cemented with a dual
      cure resin cement. The superficial dentin of human third molars was exposed and
      acid-etched and an adhesive system was applied (Single Bond 2). Four-mm-thick
      indirect resin composite restorations (Gradia) were fabricated and cemented using
      a dual-cure resin cement (Rely X). Four light sources were used to polymerize the
      cement: QTH - Optilux 401; LED1 - L.E.Demetron 1; LED2 - Optilight CL; and LED3-
      Ultralume 5. The teeth were stored for 24 h and then sectioned, yielding stick
      shaped specimens for each group with a bonded area of 1.0 mm(2). The specimens
      were then tested in a universal testing machine, at a crosshead speed of 1
      mm/min. Data were analyzed using ANOVA. Bond strength mean values were: QTH: 22.5
      (+/- 8.4); LED1: 22.7 (+/- 9.4); LED2: 21.4 (+/- 10.2); and LED3: 27.3 (+/-
      13.8). No statistically significant difference was observed among the
      experimental groups. The bond strength values when the cement was polymerized
      using different LED lights were equivalent to the values when the QTH light was
      used. It can be concluded that the variety of light sources used in the present
      study did not influence the bond strength of indirect resin composite
      restorations cemented with a dual-cure resin cement.

PMID- 18622488
TI  - Influence of intrapulpal pressure simulation on the bond strength of adhesive
      systems to dentin.
AB  - The purpose of this study was to evaluate the influence of intrapulpal pressure
      simulation on the bonding effectiveness of etch & rinse and self-etch adhesives
      to dentin. Eighty sound human molars were distributed into eight groups,
      according to the permeability level of each sample, measured by an apparatus to
      assess hydraulic conductance (Lp). Thus, a similar mean permeability was achieved
      in each group. Three etch & rinse adhesives (Prime & Bond NT - PB, Single Bond 
      SB, and Excite--EX) and one self-etch system (Clearfil SE Bond--SE) were
      employed, varying the presence or absence of an intrapulpal pressure (IPP)
      simulation of 15 cmH2O. After adhesive and restorative procedures were carried
      out, the samples were stored in distilled water for 24 hours at 37 degrees C, and
      taken for tensile bond strength (TBS) testing. Fracture analysis was performed
      using a light microscope at 40 X magnification. The data, obtained in MPa, were
      then submitted to the Kruskal-Wallis test ( a = 0.05). The results revealed that
      the TBS of SB and EX was significantly reduced under IPP simulation, differing
      from the TBS of PB and SE. Moreover, SE obtained the highest bond strength values
      in the presence of IPP. It could be concluded that IPP simulation can influence
      the bond strength of certain adhesive systems to dentin and should be considered
      when in vitro studies are conducted.

PMID- 18622489
TI  - In vitro evaluation of the effect of natural orange juices on dentin morphology.
AB  - The patient's diet has been considered an important etiological factor of dentin
      hypersensitivity. The frequent ingestion of acidic substances can promote the
      loss of dental structure or remove the smear layer. The purpose of this study was
      to evaluate the degree of smear layer removal and dentinal tubules exposure by
      different natural orange juices. Extracted human teeth were submitted to manual
      scaling in order to develop the smear layer. Seventy dentin samples were obtained
      and distributed into the following groups: Control, lime orange, lime, valencia
      orange, navel orange, mandarin, and tangerine. Each group included 2 methods of
      application: Topical and topical + friction. After preparation for SEM analysis,
      photomicrographs were assessed by a blind calibrated examiner using an index
      system. The Kruskal-Wallis test indicated a significant influence of the orange
      juices on smear layer removal. Significant difference was observed between navel
      orange, valencia orange, mandarin and the control group (p < 0.05). These orange
      juices resulted in greater removal of the smear layer and greater opening of
      dentinal tubules. The comparison between the application methods for each group
      using the Mann-Whitney test showed that friction increased smear layer removal
      significantly only for lime orange and lime. The data suggest that certain
      natural orange juices are more effective in terms of smear layer removal and
      dentinal tubules exposure than others.

PMID- 18622490
TI  - Bone regeneration in cranioplasty and clinical complications in rabbits with
      alloxan-induced diabetes.
AB  - This research evaluated the bone repair process in surgical defects created on
      the parietal bones of diabetic rabbits using the guided bone regeneration
      technique to observe the effects of alloxan in the induction of diabetes
      mellitus. Twenty-four adult rabbits were divided into three study groups: control
      (C), diabetic (D) and diabetic associated to polytetrafluoroethylene (PTFE)
      membrane (D-PTFE). For diabetes induction the animals received one dose of
      monohydrated alloxan (90 mg/kg) by intravenous administration in the auricular or
      femoral vein. In group D-PTFE the membrane covered both the floor and the surface
      of the bone defect. In groups D and C, the bone defect was filled up with blood
      clot. The specimens were fixed in 10% formol and prepared for histomorphometric
      analysis. The results showed that the 90 mg/kg dose of monohydrate alloxan was
      sufficient to promote diabetes mellitus when administered in the auricular vein.
      Bone regeneration was slower in the diabetic group when compared with the control
      and diabetic-PTFE groups, but there was no significant statistical difference
      between the two experimental groups (D and D-PTFE). The oral and general clinical
      complications among the diabetics were weight loss, polyuria, polyphagia and
      severe chronic gingivitis.

PMID- 18622491
TI  - Measurement of antioxidant activity with trifluoperazine dihydrochloride radical
      cation.
AB  - A novel, rapid and cost-effective trifluoperazine dihydrochloride (TFPH)
      decolorization assay is described for the screening of antioxidant activity. A
      chromogenic reaction between TFPH and potassium persulfate at low pH produces an
      orange-red radical cation with maximum absorption at 502 nm in its first-order
      derivative spectrum. TFPH was dissolved in distilled water to give a 100 mM
      solution. The TFPH radical cation solution was made by reacting 0.5 mL of the
      solution with K2S2O8 (final concentration: 0.1 mM) and diluting to 100 mL with 4
      M H2SO4 solution. A linear inhibition of color production was observed with
      linearly increasing amounts of antioxidants, with correlation coefficients (R(2))
      ranging from 0.999 to 0.983. The antioxidant capacity of standard solutions of an
      antioxidant was evaluated by comparing with the inhibition curve using Trolox as
      the standard. Comparison of antioxidant capacity determined with this newly
      developed TFPH assay and with the well-known 2,2'-azinobis-[3-ethylbenzthiazoline
      6-sulfonic acid] (ABTS)-persulfate decolorization assay indicated the efficacy
      and sensitivity of the procedure. The proposed assay is less expensive (costs
      about US$4 per 100 assays) and requires only 20 min for preparation of radical
      cation solution in comparison with ABTS assay, in which almost 12-16 h are
      required for preparation of a stable ABTS radical cation solution. The present
      assay has the advantage over ABTS assay that it can be used to measure the
      antioxidant activity of the samples, which are naturally found at a pH as low as
      1, because the radical cation itself has been stabilized at low pH.

PMID- 18622492
TI  - Association of polymorphisms at the ADIPOR1 regulatory region with type 2
      diabetes and body mass index in a Brazilian population with European or African
      ancestry.
AB  - Association studies between ADIPOR1 genetic variants and predisposition to type 2
      diabetes (DM2) have provided contradictory results. We determined if two single
      nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory
      regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or
      African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban
      (N = 567) areas. We detected a significant effect of ethnicity on the
      distribution of the allelic frequencies of both SNPs in these populations (EA: 
      8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G =
      0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the
      case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group 
      8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group
      10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A =
      0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G =
      0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the
      polymorphisms were associated with metabolic/anthropometric risk factors for DM2
      in any of the three populations, except for HDL cholesterol, which was
      significantly higher in AfA heterozygotes (GC = 53.75 +/- 17.26 mg/dL) than in
      homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk
      factors for DM2 or for metabolic/anthropometric measurements that represent risk
      factors for DM2 in populations of European and African ancestries.

PMID- 18622493
TI  - Hemodialysis improves endothelial venous function in end-stage renal disease.
AB  - The objective of the present study was to determine the acute effect of
      hemodialysis on endothelial venous function and oxidative stress. We studied 9
      patients with end-stage renal disease (ESRD), 36.8 +/- 3.0 years old, arterial
      pressure 133.8 +/- 6.8/80.0 +/- 5.0 mmHg, time on dialysis 55.0 +/- 16.6 months,
      immediately before and after a hemodialysis session, and 10 healthy controls
      matched for age and gender. Endothelial function was assessed by the dorsal hand
      vein technique using graded local infusion of acetylcholine (endothelium
      dependent venodilation, EDV) and sodium nitroprusside (endothelium-independent
      venodilation). Oxidative stress was evaluated by measuring protein oxidative
      damage (carbonyls) and antioxidant defense (total radical trapping antioxidant
      potential - TRAP) in blood samples. All patients were receiving recombinant human
      erythropoietin for at least 3 months and were not taking nitrates or a-receptor
      antagonists. EDV was significantly lower in ESRD patients before hemodialysis
      (65.6 +/- 10.5) vs controls (109.6 +/- 10.8; P = 0.010) and after hemodialysis
      (106.6 +/- 15.7; P = 0.045). Endothelium-independent venodilation was similar in
      all comparisons performed. The hemodialysis session significantly decreased TRAP
      (402.0 +/- 53.5 vs 157.1 +/- 28.3 U Trolox/microL plasma; P = 0.001). There was
      no difference in protein damage comparing ESRD patients before and after
      hemodialysis. The magnitude of change in the EDV was correlated negatively with
      the magnitude of change in TRAP (r = -0.70; P = 0.037). These results suggest
      that a hemodialysis session improves endothelial venous function, in association
      with an antioxidant effect.

PMID- 18622494
TI  - Prokaryotic expression of a novel mouse pro-apoptosis protein PNAS-4 and
      application of its polyclonal antibodies.
AB  - Mouse PNAS-4 (mPNAS-4) has 96% identity with human PNAS-4 (hPNAS-4) in primary
      sequence and has been reported to be involved in the apoptotic response to DNA
      damage. However, there have been no studies reported of the biological functions
      of mPNAS-4. In studies conducted by our group (unpublished data), it was
      interesting to note that overexpression of mPNAS-4 promoted apoptotic death in
      Lewis lung carcinoma cells (LL2) and colon carcinoma cells (CT26) of mice both in
      vitro and in vivo. In our studies, mPNAS-4 was cloned into the pGEX-6P-1 vector
      with GST tag at N-terminal in Escherichia coli strain BL21(DE3). The soluble and
      insoluble expression of recombinant protein mPNAS-4 (rmPNAS-4) was temperature
      dependent. The majority of rmPNAS-4 was insoluble at 37 degrees C, while it was
      almost exclusively expressed in soluble form at 20 degrees C. The soluble rmPNAS
      4 was purified by one-step affinity purification, using a glutathione Sepharose
      4B column. The rmPNAS-4 protein was further identified by electrospray ionization
      mass spectrometry analysis. The search parameters of the parent and fragment mass
      error tolerance were set at 0.1 and 0.05 kDa, respectively, and the sequence
      coverage of search result was 28%. The purified rmPNAS-4 was further used as
      immunogen to raise polyclonal antibodies in New Zealand white rabbit, which were
      suitable to detect both the recombinant and the endogenous mPNAS-4 in mouse brain
      tissue and LL2 cells after immunoblotting and/or immunostaining. The purified
      rmPNAS-4 and our prepared anti-mPNAS-4 polyclonal antibodies may provide useful
      tools for future biological function studies for mPNAS.

PMID- 18622495
TI  - The association of ACE gene D/I polymorphism with cardiovascular risk factors in
      a population from Rio de Janeiro.
AB  - Our aim was to determine the frequencies of the angiotensin-converting enzyme
      (ACE) gene alleles D and I and any associations to cardiovascular risk factors in
      a population sample from Rio de Janeiro, Brazil. Eighty-four adults were selected
      consecutively during a 6-month period from a cohort subgroup of a previous large
      cross-sectional survey in Rio de Janeiro. Anthropometric data and blood pressure
      measurements, echocardiogram, albuminuria, glycemia, lipid profile, and ACE
      genotype and serum enzyme activity were determined. The frequency of the ACE*D
      and I alleles in the population under study, determined by PCR, was 0.59 and
      0.41, respectively, and the frequencies of the DD, DI, and II genotypes were
      0.33, 0.51, and 0.16, respectively. No association between hypertension and
      genotype was detected using the Kruskal-Wallis method. Mean plasma ACE activity
      (U/mL) in the DD (N = 28), DI (N = 45) and II (N = 13) groups was 43 (in males)
      and 52 (in females), 37 and 39, and 22 and 27, respectively; mean
      microalbuminuria (mg/dL) was 1.41 and 1.6, 0.85 and 0.9, and 0.6 and 0.63,
      respectively; mean HDL cholesterol (mg/dL) was 40 and 43, 37 and 45, and 41 and
      49, respectively, and mean glucose (mg/dL) was 93 and 108, 107 and 98, and 85 and
      124, respectively. A high level of ACE activity and albuminuria, and a low level
      of HDL cholesterol and glucose, were found to be associated with the DD genotype.
      Finally, the II genotype was found to be associated with variables related to
      glucose intolerance.

PMID- 18622496
TI  - Correlation of serum leptin and insulin levels of pregnant protein-restricted
      rats with predictive obesity variables.
AB  - During pregnancy and protein restriction, changes in serum insulin and leptin
      levels, food intake and several metabolic parameters normally result in enhanced
      adiposity. We evaluated serum leptin and insulin levels and their correlations
      with some predictive obesity variables in Wistar rats (90 days), up to the 14th
      day of pregnancy: control non-pregnant (N = 5) and pregnant (N = 7) groups
      (control diet: 17% protein), and low-protein non-pregnant (N = 5) and pregnant (N
      = 6) groups (low-protein diet: 6%). Independent of the protein content of the
      diet, pregnancy increased total (F1,19 = 22.28, P < 0.001) and relative (F1,19 =
      5.57, P < 0.03) food intake, the variation of weight (F1,19 = 49.79, P < 0.000)
      and final body weight (F1,19 = 19.52, P < 0.001), but glycemia (F1,19 = 9.02, P =
      0.01) and the relative weight of gonadal adipose tissue (F1,19 = 17.11, P <
      0.001) were decreased. Pregnancy (F1,19 = 18.13, P < 0.001) and low-protein diet
      (F1,19 = 20.35, P < 0.001) increased the absolute weight of brown adipose tissue.
      However, the relative weight of this tissue was increased only by protein
      restriction (F1,19 = 15.20, P < 0.001) and the relative lipid in carcass was
      decreased in low-protein groups (F1,19 = 4.34, P = 0.05). Serum insulin and
      leptin levels were similar among groups and did not correlate with food intake.
      However, there was a positive relationship between serum insulin levels and
      carcass fat depots in low-protein groups (r = 0.37, P < 0.05), while in pregnancy
      serum leptin correlated with weight of gonadal (r = 0.39, P < 0.02) and
      retroperitoneal (r = 0.41, P < 0.01) adipose tissues. Unexpectedly, protein
      restriction during 14 days of pregnancy did not alter the serum profile of
      adiposity signals and their effects on food intake and adiposity, probably due to
      the short term of exposure to low-protein diet.

PMID- 18622497
TI  - Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with
      gastric cancer.
AB  - Gastric cancer is the forth most frequent malignancy and the second most common
      cause of cancer death worldwide. DNA methylation is the most studied epigenetic
      alteration, occurring through a methyl radical addition to the cytosine base
      adjacent to guanine. Many tumor genes are inactivated by DNA methylation in
      gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and
      TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric
      cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil.
      All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples
      were surgically obtained at the Joao de Barros Barreto University Hospital, State
      of Para, and were stored at -80 degrees C before DNA extraction. Patients had
      never been submitted to chemotherapy or radiotherapy, nor did they have any other
      diagnosed cancer. None of the gastric cancer samples presented methylated DNA
      sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal
      gastric mucosa; however, the CDKN2A promoter was methylated in 30.4% of gastric
      cancer samples, with 35% methylation in diffuse-type and 26.9% in intestinal-type
      cancers. CDKN2A methylation was associated with the carcinogenesis process for
      ~30% diffuse-type and intestinal-type compared to non-neoplastic samples. Thus,
      ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis
      in our samples. CDKN2A can be implicated in the carcinogenesis process of only a
      subset of gastric neoplasias.

PMID- 18622498
TI  - [Childhood wheezing].

PMID- 18622499
TI  - [Evaluation of acute bacterial rhinosinusitis in asthma patients based on
      clinical parameters and imaging studies, together with ear, nose and throat
      examination].
AB  - OBJECTIVE: To evaluate paranasal sinuses in patients with stable or acute asthma
      in order to determine the prevalence of acute bacterial rhinosinusitis. METHODS:
      A cross-sectional study including 30 patients with acute asthma (73% females)
      treated in the emergency room and 30 patients with stable asthma (80% females)
      regularly monitored as outpatients. All patients completed a questionnaire on
      respiratory signs and symptoms and were submitted to ear, nose and throat (ENT)
      examination, as well as to X-ray and computed tomography (CT) imaging of the
      sinuses. RESULTS: Based on the clinical diagnosis, the prevalence of acute
      bacterial rhinosinusitis was 40% in the patients with acute asthma and 3% in
      those with stable asthma. The ENT examination findings and the imaging findings
      in isolation were not useful to confirm the diagnosis. CONCLUSIONS: In
      themselves, ENT examination findings, X-ray findings and CT findings were not
      useful for the diagnosis of acute bacterial rhinosinusitis. Our results provide
      further evidence that a clinical diagnosis of bacterial rhinosinusitis should be
      made with caution.

PMID- 18622500
TI  - [Wheezing phenotypes from birth to adolescence: a cohort study in Pelotas,
      Brazil, 1993-2004].
AB  - OBJECTIVE: To study the prevalence of wheezing patterns and their associations
      with independent variables. METHODS: Cohort study of live births in 1993 in
      Pelotas, Brazil. A systematic subsample (20%) of the original cohort was
      evaluated at 6 months, 12 months and 4 years. At 10-12 years, 87.5% of the
      original cohort was contacted. Wheezing was categorized: transient, wheezing at 4
      years but not at 10-12; persistent, wheezing at all evaluations; late-onset,
      wheezing at 10-12 years. Independent variables were analyzed: gender; skin color;
      family income; smoking/asthma during pregnancy; breastfeeding; respiratory
      infection/diarrhea (during the 1st year); family members with asthma/allergy (at
      4 years and at 10-12); physician-diagnosed rhinitis/eczema (at 10-12 years).
      RESULTS: The subsample comprised 897 adolescents. Wheezing patterns were
      expressed as prevalence (95% CI): transient, 43.9% (40.7-47.2); persistent, 6.4%
      (4.8-8.0); and late-onset, 3.3% (2.2-4.5). The transient pattern was more common
      in children from low-income families, children breastfed for less time, children
      with a history of respiratory infections (during the 1st year) and children with
      asthma in the family (at 4 years). The persistent pattern was almost twice as
      common in males, in children whose mothers had asthma during pregnancy, in
      children with respiratory infections (during the 1st year) and in children with
      asthma in the family (at 4 and 10-12 years). The late-onset pattern was more
      prevalent among those with asthma in the family (at 10-12 years) and those
      diagnosed with rhinitis (at 10-12 years), being less prevalent among those
      reporting respiratory infections (during the 1st year) and those diagnosed with
      eczema (at 10-12 years). CONCLUSIONS: Knowledge of the associations of wheezing
      patterns allows us to adopt preventive and therapeutic measures.

PMID- 18622501
TI  - [Symptoms of obstructive sleep apnea-hypopnea syndrome in children].
AB  - OBJECTIVE: To investigate the symptoms most frequently found in children with a
      polysomnographic diagnosis of obstructive sleep apnea-hypopnea syndrome (OSAHS).
      METHODS: We evaluated 38 children consecutively referred to the sleep laboratory
      with suspicion of OSAHS between June of 2003 and December of 2004. The patients
      were submitted to a pre-sleep questionnaire and to polysomnography. RESULTS: The
      mean age was 7.8 +/- 4 years (range, 2-15 years), and 50% of the children were
      male. Children without apnea accounted for 7.9% of the sample. The obstructive
      sleep apnea observed in the remainder was mild in 42.1%, moderate in 28.9% and
      severe in 22.1%. Severe cases of apnea were most common among children under the
      age of six (pre-school age). In children with OSAHS, the most common symptoms
      were snoring and nasal obstruction, which were observed in 74.3 and 72.7% of the
      children, respectively. Excessive sleepiness and bruxism were seen in 29.4 and
      34.3%, respectively, and reflux disease was seen in only 3.1%. Restless legs and
      difficulty in falling asleep were identified in 65 and 33%, respectively. All of
      the children diagnosed with severe OSAHS also presented snoring and bruxism.
      CONCLUSIONS: Snoring and nasal obstruction were the most common symptoms found in
      our sample of children and adolescents with OSAHS. In addition, OSAHS severity
      was associated with being in the lower age bracket.

PMID- 18622502
TI  - [Pulmonary involvement in Behcet's disease: a positive single-center experience
      with the use of immunosuppressive therapy].
AB  - OBJECTIVE: Behcet's syndrome, or Behcet's disease (BD), is a multisystem
      pathology, and survival is related to pulmonary involvement. However, it appears
      that different treatments correlate with different prognoses. The aim of this
      study was to evaluate clinical and tomographic evolution, as well as the
      survival, of patients with BD-related pulmonary involvement. METHODS: A
      retrospective review of our experience with pulmonary manifestations in patients
      with BD treated at our institution between January 1, 1988 and April 30, 2006.
      The clinical, radiological, treatment and survival data were obtained from
      medical charts. RESULTS: We identified 9 patients with BD-related pulmonary
      involvement. The mean age was 34 +/- 11.5 years, and 7 of the patients were male.
      The radiological findings were as follows: pulmonary artery aneurysm (PAA) in 8
      patients; pulmonary embolism in 3 (translating to an incidence of 5.11 cases/100
      patient-years); alveolar hemorrhage in one; and pulmonary hypertension in one.
      The treatment consisted of immunosuppression with prednisone plus chlorambucil
      (or cyclophosphamide or mycophenolate mofetil) in all patients, with partial or
      complete resolution of the PAAs. One patient with a PAA and pulmonary
      hypertension also received sildenafil and warfarin, with good clinical and
      tomographic response (the first report in the English literature). In our sample,
      the mean duration of the follow-up period was 6.52 years. The three-year survival
      rate was 88.8%, as was the five-year survival rate. CONCLUSIONS: Patients with BD
      related pulmonary involvement can present good survival with immunosuppressive
      therapy, and BD should be borne in mind as a possible cause of pulmonary
      hypertension and alveolar hemorrhage.

PMID- 18622503
TI  - [Occupational exposure and occurrence of pneumoconioses in Campinas, Brazil, 1978
      2003].
AB  - OBJECTIVE: To develop and consolidate a comprehensive database on the occurrence
      of pneumoconioses in an industrialized region of Brazil, with a special focus on
      the activities most frequently related to these diseases. METHODS: A
      retrospective, observational study was conducted in order to gather data on cases
      of pneumoconioses treated at the outpatient clinic of the State University at
      Campinas Hospital das Clinicas between 1978 and 2003. Individuals diagnosed with
      pneumoconiosis, based on their occupational history and on chest X-ray findings
      of abnormalities consistent with interstitial lung disease involving the
      parenchyma, in accordance with the 1980 and 2000 recommendations of the
      International Labour Organization, were included in the study. RESULTS: A total
      of 1147 cases of pneumoconiosis were identified (1075 in males and 72 in
      females): 1061 cases of silicosis (92.5%); 51 cases of mixed-dust pneumoconiosis
      (4.45%); 15 cases of asbestosis (1.31%); 13 cases of phosphate rock-related
      pneumoconiosis (1.13%); and 7 cases of other types of pneumoconiosis (0.6%),
      including those related to exposure to coal, graphite and hard metals. The most
      common chest X-ray findings were 1/0, 1/1 or 1/2 profusion and small regular
      opacities (p, q or r), although 192 patients (16.74%) presented large opacities.
      There has been a substantial decline in the occurrence of the disease since the
      1990s, and the duration of exposure was typically shorter than that observed in a
      study conducted in the United States. CONCLUSIONS: Our findings have been
      compiled into a comprehensive database for the investigation of pneumoconiosis in
      an industrialized area of Brazil. These data make it possible to conduct follow
      up studies and develop health policies related to occupational respiratory
      disorders.

PMID- 18622504
TI  - [Immediate bronchodilator response to formoterol in poorly reversible chronic
      obstructive pulmonary disease].
AB  - OBJECTIVE: To evaluate, using pulmonary function tests, the effectiveness of
      formoterol as a bronchodilator at 30 min after its administration in patients
      with poorly reversible COPD. METHODS: A prospective study including 40 COPD
      patients not responding to the short-acting bronchodilator used in the
      spirometric test-variation of less than 200 mL and less than 7% of predicted in
      forced expiratory volume in one second (FEV1). All patients were classified as
      having stage II, III, or IV COPD (Brazilian Thoracic Society/Global Initiative
      for Chronic Obstructive Lung Disease) and presented FEV1 < 70% of predicted
      value. The patients were randomized into two groups of 20, with similar clinical
      characteristics, receiving, via a dry powder inhaler, either formoterol or a
      placebo. The pulmonary function testing (plethysmography) was repeated at 30 min
      after formoterol or placebo administration. RESULTS: In the formoterol group, the
      mean values obtained for FEV1, inspiratory capacity, and forced vital capacity
      were significantly greater than those obtained in the placebo group (p = 0.00065,
      p = 0.05, and p = 0.017, respectively), whereas that obtained for airway
      resistance was significantly lower (p = 0.010). Less pronounced differences were
      observed for residual volume, vital capacity and specific airway conductance,
      which were lower, higher and higher, respectively, in the formoterol group.
      CONCLUSIONS: In COPD patients not responding to the short-acting bronchodilator
      used in the spirometric test, formoterol promoted significant improvement in lung
      function at 30 min after of administration. Further studies are required to
      confirm whether formoterol can also be used as a medication for immediate relief
      of symptoms in COPD.

PMID- 18622505
TI  - [Effects of manually assisted coughing on respiratory mechanics in patients
      requiring full ventilatory support].
AB  - OBJECTIVE: Manually assisted coughing (MAC) consists of a vigorous thrust applied
      to the chest at the beginning of a spontaneous expiration or of the expiratory
      phase of mechanical ventilation. Due to routine use of MAC in intensive care
      units, the objective of this study was to assess the effects of MAC on
      respiratory system mechanics in patients requiring full ventilatory support.
      METHODS: We assessed 16 sedated patients on full ventilatory support (no active
      participation in ventilation). Respiratory system mechanics and oxyhemoglobin
      saturation were measured before and after MAC, as well as after endotracheal
      aspiration. Bilateral MAC was performed ten times on each patient, with three
      respiratory cycle intervals between each application. RESULTS: Data analysis
      demonstrated a decrease in resistive pressure and respiratory system resistance,
      together with an increase in oxyhemoglobin saturation, after MAC combined with
      endotracheal aspiration. No evidence of alterations in peak pressures, plateau
      pressures or respiratory system compliance change was observed after MAC.
      CONCLUSIONS: The use of MAC alters respiratory system mechanics, increasing
      resistive forces by removing secretions. The technique is considered safe and
      efficacious for postoperative patients. Using MAC in conjunction with
      endotracheal aspiration provided benefits, achieving the proposed objective: the
      displacement and removal of airway secretions.

PMID- 18622506
TI  - [Assessment of the quality of life of patients with lung cancer using the Medical
      Outcomes Study 36-item Short-Form Health Survey].
AB  - OBJECTIVE: To assess the quality of life of patients with lung cancer and to
      compare it with that of individuals without cancer. METHODS: The Medical Outcomes
      Study 36-item Short-Form Health Survey (SF-36) was administered to 57 patients
      diagnosed with lung cancer, treated at the Lung Cancer Outpatient Clinic of the
      Hospital Sao Paulo, and to a control group of 57 individuals recruited from the
      Extra Penha workout group. The Mann-Whitney test was used to compare the groups,
      domain by domain. The first model of logistic regression was adjusted for male
      gender, nonsurgical treatment, Karnofsky performance status and smoking, which
      were included as predictors. The second model was adjusted for each SF-36 domain
      in order to identify increases in the proportions of patients in stage IIIB or
      IV. RESULTS: The lung cancer group and the control group presented the following
      mean scores, respectively, for the SF-36 domains: role limitations due to
      physical health problems, 29.39 +/- 36.94 and 82.89 +/- 28.80; role limitations
      due to emotional problems, 42.78 +/- 44.78 and 86.55 +/- 28.77; physical
      function, 56.49 +/- 28.39 and 89.00 +/- 13.80; vitality, 61.61 +/- 23.82 and
      79.12 +/- 17.68; bodily pain, 62.72 +/- 28.72 and 81.54 +/- 19.07; general
      health, 62.51 +/- 25.57 and 84.47 +/- 13.47; emotional well-being, 68.28 +/-
      23.46 and 82.63 +/- 17.44; and social functioning, 72.87 +/- 29.20 and 91.67 +/-
      17.44. The logistic regression model showed that role limitations due to physical
      health problems, physical function and emotional well-being were predictors of
      stages IIIB and IV. CONCLUSIONS: The patients with lung cancer had a poorer
      quality of life, especially regarding physical aspects, than did the control
      subjects.

PMID- 18622507
TI  - [Treatment outcome and laboratory confirmation of tuberculosis diagnosis in
      patients with HIV/AIDS in Recife, Brazil].
AB  - OBJECTIVE: To compare the frequency of unfavorable outcome (death or default and
      treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for
      TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients
      who were so treated without diagnostic confirmation. METHODS: A retrospective
      cohort of TB/HIV co-infected patients who started TB treatment between July of
      2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main
      exposure variable, laboratory confirmation of TB, was adjusted for three
      different sets of variables: sociodemographic variables; HIV/AIDS-related
      variables; and TB-related variables. In order to evaluate the statistical
      significance of the results, we calculated odds ratios, with 95% confidence
      intervals, and p values (from chi-square tests and likelihood ratio tests).
      RESULTS: A total of 262 patients were studied. No association was found between
      laboratory confirmation of the diagnosis of TB at treatment outset and
      unfavorable outcome, even after adjustment for confounders. In the final multiple
      logistic regression model, the following variables remained: the presence of
      other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm(3); viral
      load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB;
      and change in the TB treatment regimen due to adverse reactions or intolerance.
      CONCLUSIONS: Our results suggest that TB treatment in TB/HIV co-infected patients
      without etiologic confirmation of TB, at the discretion of experienced physicians
      in referral centers, did not increase the risk of unfavorable outcomes. In
      addition, it allowed the identification of groups that should be closely
      monitored due to a greater risk of unfavorable outcomes.

PMID- 18622508
TI  - [Accuracy of inpatient and outpatient gastric lavage in the diagnosis of
      pulmonary tuberculosis in children].
AB  - OBJECTIVE: To compare gastric lavage (GL) performed in inpatients with GL
      performed in outpatients in terms of its accuracy in diagnosing pulmonary
      tuberculosis (TB) in children. METHODS: A prospective study was carried out in
      the state of Espirito Santo, Brazil, from 1999 to 2003. A total of 230 children
      suspected of having TB (103 inpatients and 127 outpatients) were selected to
      undergo GL. Those thus diagnosed with TB (n = 53) were divided into two groups:
      inpatient GL (n = 30) and outpatient GL (n = 23). All 53 children were monitored
      for 6 months in order to evaluate the accuracy of the diagnosis. Accuracy was
      determined based on any change in diagnosis, cure rate, and the percentage of
      positive cultures in the two groups studied. RESULTS: The cure rate was 100% in
      both groups, and there was no change in diagnosis in the 53 children studied. No
      significant difference was found between the two groups studied in terms of
      detection of Mycobacterium tuberculosis (RR = 1.47; 95% CI: 0.95-2.27; p =
      0.095), although the outpatient group presented a greater rate of positive
      cultures. CONCLUSIONS: Our results show that the accuracy of GL performed in an
      inpatient setting is similar to that of GL performed in an outpatient setting.
      This indicates that hospitalization is required only in more severe cases in
      which GL cannot be performed as an outpatient procedure.

PMID- 18622509
TI  - [Role of nitric oxide in the control of the pulmonary circulation: physiological,
      pathophysiological, and therapeutic implications].
AB  - Nitric oxide (NO) is an endogenous vasoactive compound that contributes to
      pulmonary vascular homeostasis and is produced by three nitric oxide synthase
      (NOS) isoforms-neuronal NOS (nNOS); inducible NOS (iNOS); and endothelial NOS
      (eNOS)-all three of which are present in the lung. Studies using pharmacological
      inhibitors or knockout mice have shown that eNOS-derived NO plays an important
      role in modulating pulmonary vascular tone and attenuating pulmonary
      hypertension. However, studies focusing on the role of iNOS have shown that this
      isoform contributes to the pathophysiology of acute lung injury and acute
      respiratory distress syndrome. This review aimed at outlining the role played by
      NO in the control of pulmonary circulation, both under physiological and
      pathophysiological conditions. In addition, we review the evidence that the L
      arginine-NO-cyclic guanosine monophosphate pathway is a major pharmacological
      target in the treatment of pulmonary vascular diseases.

PMID- 18622510
TI  - [Negative-pressure pulmonary edema and hemorrhage associated with upper airway
      obstruction].
AB  - Negative-pressure pulmonary edema accompanied by hemorrhage as a manifestation of
      upper airway obstruction is an uncommon problem that is potentially life
      threatening. The principal pathophysiological mechanism involved is the
      generation of markedly negative intrathoracic pressure, which leads to an
      increase in pulmonary vascular volume and pulmonary capillary transmural
      pressure, creating a risk of disruption of the alveolar-capillary membrane. We
      report the case of an adult male with diffuse alveolar hemorrhage following acute
      upper airway obstruction caused by the formation of a cervical and mediastinal
      abscess resulting from the insertion of a metallic tracheal stent. The patient
      was treated through drainage of the abscess, antibiotic therapy, and positive
      pressure mechanical ventilation. This article emphasizes the importance of
      including this entity in the differential diagnosis of acute lung injury after
      procedures involving upper airway instrumentation.

PMID- 18622511
TI  - [A rare case of pneumothorax: metastatic adamantinoma].
AB  - Here, we describe two cases of lung metastasis of adamantinoma of long bones, a
      low-grade bone neoplasm that rarely metastasizes. In both cases, the clinical
      presentation of the metastases was characterized by spontaneous pneumothorax
      secondary to tumor cavitation, a phenomenon described in only three of the
      studies reviewed in the literature. Clinical, radiological, and
      anatomopathological findings, as well as the procedures adopted in the two cases,
      are described.

PMID- 18622512
TI  - [Therapeutic application of collateral ventilation in diffuse pulmonary
      emphysema: study protocol presentation].
AB  - We present a protocol to test a new surgical procedure for the treatment of
      patients with diffuse lung emphysema who, after having received the golden
      standard treatment (pulmonary rehabilitation), continue to present respiratory
      failure with disabling dyspnea. Ten patients with severe lung hyperinflation will
      be evaluated. The method proposed is designed to create alternative expiratory
      passages for air trapped in the emphysematous lung by draining the lung
      parenchyma, thereby establishing communication between the alveoli and the
      external environment. The ten patients selected will be required to meet the
      inclusion criteria and to give written informed consent. Those ten patients will
      be included in the study pending the approval of the Ethics in Research Committee
      of the Sao Paulo Santa Casa School of Medicine, Sao Paulo, Brazil. The protocol
      we will employ in order to evaluate the proposed procedure is feasible and will
      show whether debilitated patients suffering from diffuse pulmonary emphysema can
      benefit from this procedure, which could represent an alternative to lung
      transplant or lung volume reduction surgery, the only options currently
      available.

PMID- 18622513
TI  - Evidence based practice in the field of the speech, language and hearing
      sciences. Editorial.

PMID- 18622514
TI  - [Assessment of self-representation abilities in seven-, eight-year-old children].
AB  - BACKGROUND: Theory of Mind. AIM: the purpose of this study was to assess the self
      representation abilities in 7-8 year old children and to verify the relationship
      between the Theory of Mind and language. METHOD: subjects of this study were 100
      children - 50 boys and 50 girls - with ages between 7:2 and 8:11, divided in four
      groups: 7-year-old children with no communication deficits (Group 1), with 37
      subjects; 7-year-old children with phonological retard (Group 2), with 13
      subjects; 8-year-old children with no communication deficits (Group 3), with 46
      subjects; and 8- year- old children with phonological retard (Group 4), with 4
      subjects. All of the subjects were students of a municipal school in the city of
      Sao Paulo and were submitted to speech, language and hearing tests prior to the
      assessment of the self-representation abilities. The assessment of the self
      representation abilities is composed by four tests proposed by Fernandes (2002)
      and adapted by Mecca (2005). RESULTS: 88% of the 7-year-old subjects passed the
      self-representation abilities test; 92% of the 8-year-old subjects also passed
      the same test. No statistically significant differences were found between
      gender, age or group. CONCLUSION: generally, children around 7 years have already
      acquired the Theory of Mind, however this acquisition can take longer and occur
      at other ages. The type of interaction and the presence of abstract elements
      during conversation can have an influence on the children's performance in tasks
      involving the theory of mind.

PMID- 18622515
TI  - [Influence of speech rate and loudness on speech intelligibility].
AB  - BACKGROUND: contextual cues intrinsic to speech stimuli can have an influence on
      speech intelligibility measurements; however, the influence of cues that depend
      on the acoustic signal, such as speech rate and vocal loudness, need further
      investigation. AIM: to examine whether possible reductions in the articulatory
      rate and increase in vocal loudness, associated to the production of different
      speech stimuli, can have an influence on speech intelligibility measurements.
      METHOD: participants of this study were thirty normal speakers and sixty normal
      listeners. Speakers were recorded during the repetition of three lists of speech
      stimuli (sentences, words and pseudo words). The averages of the articulatory
      rate (syllables per second) and of the vocal loudness (decibel) were calculated
      for each speaker according to their performance in each repetition task. Speech
      intelligibility was measured based on the orthographic transcription of the
      speech samples; the score was calculated in terms of percentage of correctly
      transcribed words. RESULTS: it was observed that articulatory rates were
      statistically different between the three types of stimuli; however, the stimuli
      produced with the lowest articulatory rate (pseudo words followed by words) did
      not present higher speech intelligibility scores. Vocal loudness was
      statistically higher during the repetition of pseudo words; however, this
      increase did not have an influence on the speech intelligibility scores.
      CONCLUSION: the reduction of the articulatory rate or the increase of vocal
      loudness did not have an influence on the speech intelligibility measurements,
      indicating that contextual cues have a greater impact on speech intelligibility
      than the independent cues given by the acoustic signal.

PMID- 18622516
TI  - [Narration of stories by children with specific language impairment].
AB  - BACKGROUND: narrative abilities provide rich information about the linguistic,
      cognitive and social competences of children with typical language development
      and with SLI (Specific Language Impairment). Children with SLI present deficits
      in speech elaboration, which is generally confusing and repetitive. Furthermore,
      there may be difficulty with text organization, understanding the underlying time
      and cause-effect relationships and in the development of the structural knowledge
      needed for comprehension. AIM: to characterize the narration of stories by
      children with SLI regarding the type and content of speech and to compare their
      performance to that of their typically developing peers, matched according to the
      chronological age. METHOD: two groups participated in this study: Control Group
      (CG), 24 children with no language deficits and Research Group (RG), 8 children
      with the diagnosis of SLI. To elicit the narratives, a series of 15 stories were
      used, represented by illustrations containing four scenes each. These sequences
      were created and classified as mechanical, behavioral and intentional, according
      to the relationship established between the characters. RESULTS: children with
      SLI presented poorer narratives when compared to their typically developing
      peers, independent of the type of story which was presented. Moreover, children
      with SLI showed a similar perception of the mental states when compared to
      children with normal development. CONCLUSIONS: these results indicate that,
      regardless the type of story, children with SLI have difficulties in the use of
      language, that is, with the linguistic abilities necessary to narrate stories and
      not in the perception of the characters' mental state.

PMID- 18622517
TI  - [Presbyvertigo as a cause of dizziness in elderly].
AB  - BACKGROUND: dizziness is a frequent complaint in the geriatric population and has
      a negative impact in the life quality of these individuals. AIM: to correlate the
      types of dizziness and alterations in the caloric test and to verify the
      frequency of presbyvertigo in an elderly population with dizziness. METHOD: The
      records of 132 patients aged over 60 and with balance disturbance were reviewed.
      These patients were evaluated in the Otoneurology Service of the Clinical
      Hospital of the Federal University of Minas Gerais between the years of 1998 and
      2007. The variables considered for analysis were: epidemiologic data, clinical
      history, associated diseases and the result of the caloric test. Patients with
      positional and central vertigo were excluded from the analysis. RESULTS: The
      research sample consisted of 120 patients, with an average age was of 70 years,
      being 71% (n=87) of sample women. Vertigo with the duration of a few minutes and
      of a daily frequency was the most frequent type of dizziness. In relation to the
      caloric test, normal results were observed in 73% of the sample. Altered results
      included unilateral weakness (14%), bilateral weakness (10%) and hyperactive
      caloric response (3%). Correlating the caloric test with the type of dizziness,
      bilateral weakness was associated with postural instability (p=0.006; IC=2 -
      419). CONCLUSION: dizziness in elderly has many causes. Bilateral weakness of the
      vestibular function can be related to presbyvertigo and must be considered in
      aged individuals who present unbalance. Metabolic, psychiatric, disautonomic,
      orthopedic, visual and proprioceptive disturbances may be the cause of dizziness
      in aged individuals who present normal vestibular evaluation.

PMID- 18622518
TI  - [Auditory steady-state response in the auditory evaluation: clinical
      application].
AB  - BACKGROUND: the auditory steady state response (ASSR) is an electrophysiological
      procedure that evaluates, at the same time, the hearing thresholds of both ears
      at various frequencies. This procedure reduces the time of testing and enables
      the stimulation of levels close to 125dB HL, characterizing residual hearing.
      AIM: to verify the applicability of the ASSR to determine the hearing thresholds
      in different levels of sensorineural hearing loss. METHOD: 48 individuals aged 7
      30 years, with different levels of hearing loss were assessed. The Pure tone
      Audiometry (PTA) and the ASSR were carried out in following carrier frequencies
      0.5; 1; 2 and 4k Hz. The carrier frequencies in the ASSR were modulated in
      amplitude and frequency, with multiple dicotic stimulation for mild and moderate
      hearing loss. Simple stimulation was used to test the other hearing deficit
      levels. RESULTS: there was a significant association (p<0.01) between the
      thresholds obtained in the PTA and in the ASSR for all of the tested frequencies,
      especially for the severe levels. However, for some patients, the hearing loss
      level was overestimated in the ASSR. CONCLUSION: the ASSR can be used to estimate
      the PTA threshold; nevertheless, it should not be analyzed in an isolated way,
      but seen as a complementary procedure to the behavioral auditory assessment.

PMID- 18622519
TI  - [Relations between the Autistic Behavior Checklist (ABC) and the functional
      communicative profile].
AB  - BACKGROUND: language and communication disorders are proposed as one of the three
      fundamental criteria for the description or diagnosis of pervasive developmental
      disorders (PDD), along with social disabilities and a narrow focus of interest.
      This way, the determination of simple procedures that can be used by health and
      education professionals to identify the persons that need specialized services is
      essential. The Autistic Behavior Checklist (ABC) is being used in several studies
      because it allows simple application and may be based on filmed behavior samples,
      interviews with parents or therapists. Its' results, on the other side, had been
      tested for a few decades and been shown reliable. AIM: the general aim of this
      study is to verify the possibility that the assessment of the relation between
      communicative profile and the ABC score contributes to the diagnostic process of
      persons with disorders of the autistic spectrum. METHOD: subjects were 117
      children and adolescents with ages between 2 and 16 years attending language
      therapy. RESULTS: were statistically analyzed and indicated that there are
      negative correlations between the ABC scores and communicative interaction and
      complexity. The small amount of correlations between language sub-scale and the
      other data suggest that there is a dissociation of the description provided by
      the ABC and the criteria proposed by the DSM-IV and the ICD-10 to the diagnosis
      of autism. CONCLUSION: the search for objective criteria to determine subgroups
      of the autistic spectrum remains a challenge.

PMID- 18622520
TI  - [Relationship between the motor development of the body and the acquisition of
      oral skills].
AB  - BACKGROUND: the literature points to the influence of body posture on the oral
      skills of children which sensorimotor deficits. Only a few studies with normal
      children exist on this subject. AIM: to study the relationship between motor
      skills and oral motor skills in children, from the first day of life to 24 months
      of age. METHOD: 42 children were video recorded at the first day of life, and at
      1, 2, 3, 4, 5, 6, 9, 12 and 24 months of age. Recordings were made in the
      following postures: supine, prone, seated, standing and during breast and bottle
      feeding (until 5 months), using spoon (puree: 3 - 12 months); cup (water or
      juice: 6 - 24 months) and eating solid food (6 -24 months). Quantitative scores
      for body motor development and oral skills were established; and for the
      statistical analysis the Pearson Correlation Coefficient Test was used with a
      significance level of 5%. RESULTS: the results of motor development point to
      similar data between supine, prone, seated and standing positions; for the oral
      motor skills (during feeding/ breastfeeding, using spoon, cup and chewing). A
      similarity was observed in the acquisition of motor abilities related to the
      lips, tongue and jaw in each of the feeding situations. There was an association
      between the motor and the oral motor skills; the results indicate that the motor
      development (motor skills) occurred prior to the development of the oral skills
      from the 5th to 24 months and that the skills related to the jaw when using a cup
      and spoon occurred prior to the development of the skills related to the lips and
      tongue. CONCLUSION: there was a growing increase in the acquisition of motor and
      oral skills along the ages, as well as a variability of skills in the ages
      between the 3rd and 24 months and a significant association between the motor and
      oral skills.

PMID- 18622521
TI  - [Brainstem auditory evoked potentials as a method to assist the diagnosis of
      brain death].
AB  - BACKGROUND: brainstem auditory evoked potentials in brain death. AIM: to verify
      the agreement between the response in the auditory brainstem audiometry and the
      clinical outcome, analyzing the pattern of responses to electric stimulation.
      METHOD: a cross-sectional study performed in 30 patients with Glasgow coma score
      of 3, submitted to the auditory brainstem audiometry and followed up until their
      clinical outcome: recovery or death. The test was considered positive to brain
      death when there was no registry of waves or when there was only the registry of
      wave I; and negative when there were two or more waves, independently of their
      latencies. RESULTS: Among the patients who presented positive results for brain
      death (86.66%), all died; the only patient who recovered presented a negative
      result, indicating a specificity of 100%. Internal consistency of data was also
      observed, with an intraclass correlation coefficient of 0.562, obtained using the
      Cronbach s test; and a significant agreement between the test and the clinical
      outcome using the Kappa s test, with a confidence interval of 95% (K = 0.545; p =
      0.015). CONCLUSION: in the present study, the brainstem auditory evoked potential
      demonstrated to be highly specific in death prediction of patients in Glasgow
      coma score of 3, and was useful in assisting the diagnosis of brain death.

PMID- 18622522
TI  - [Fluency shaping with surface electromyography: a pilot study].
AB  - BACKGROUND: the use of a technological resource in fluency promotion. AIM: to
      verify the effectiveness of a stuttering treatment based on the use of surface
      electromyography (SEMG) exclusively. METHOD: participants were four stuttering
      adults of both genders. Assessment, pre and post-treatment, consisted of a speech
      gathering session and the analyses of the rest tension and of the reaction time
      for speech. Treatment consisted of twelve twenty minute training sessions
      monitored by SEMG. RESULTS: there was a statistically significant reduction in
      the number of stuttering-like disfluencies (p = 0.094) and in the number of other
      disfluencies (p = 0.014). The other parameters, as well as differences in the
      electromyographic measurements, did not present significant variation.
      CONCLUSION: SEMG proved to be effective in the reduction of stuttering, with no
      need of association to other techniques.

PMID- 18622523
TI  - [The large vestibular aqueduct syndrome: a cause of neurosensory dysacusia].
AB  - BACKGROUND: the large vestibular aqueduct syndrome (LVAS) is characterized by the
      enlargement of the vestibular aqueduct associated with sensorioneural hearing
      loss. The level of hearing loss varies and may be fluctuant, progressive or
      sudden. Vestibular symptoms may be present. The diagnosis is reached by imaging
      methods. AIM: To report an LVAS case. METHOD: a female infant was submitted to a
      computerized tomography of the ears and to audiologic tests. RESULTS: enlargement
      of the vestibular aqueduct of more than 1.5mm and sensorioneural hearing loss in
      the right ear were observed. CONCLUSION: with an early hearing evaluation it is
      possible to diagnose hearing loss, even in children were this loss is unilateral.
      Although the literature indicates that the diagnosis of LVAS occurs at a later
      age, in this case the etiologic diagnosis was enabled by computerized tomography.

PMID- 18622524
TI  - The current burden of allergic rhinitis amongst primary care practitioners and
      its impact on patient management.
AB  - AIMS: To investigate the burden of allergic rhinitis (AR) amongst primary care
      practitioners (PCPs), the impact of AR on PCPs' professional lives, and the
      effect on their management of AR patients of PCPs' personal experience of AR.
      METHODS: An online questionnaire was completed by 1201 PCPs (50% AR sufferers)
      from eight countries. RESULTS: 21% of PCPs reported very well controlled symptoms
      and 66% quite good control. Six hours work per week, on average, was missed by
      PCPs whose AR symptoms resulted in absence. AR symptoms affected concentration,
      stress level, mood, time spent with patients, physical contact with patients, and
      patient throughput. PCPs with AR reported a significantly higher proportion of AR
      patients in their practice and gave a significantly higher ranking to specific
      treatment requests and emotional well-being, and gave a significantly lower
      ranking to preventing comorbidity development and providing a treatment most
      likely to result in high patient compliance. DISCUSSION: This is the first study
      demonstrating the impact of AR on PCPs showing association with lost
      productivity, absenteeism and reduction in professional performance. Personal
      experience of AR significantly influences PCPs' management of AR and may improve
      their AR diagnostic ability.

PMID- 18622525
TI  - National study of asthma quality of life--application of the Asthma Quality of
      Life Questionnaire (AQLQ-M) by Marks in the Portuguese population.
AB  - The Portuguese version of the Marks Asthma Quality of Life Questionnaire (AQLQ-M)
      has already proven to have good diagnostic properties, and is suitable for use
      with Portuguese asthma patients. The last forty years have seen a worldwide rise
      in the rate, morbidity, mortality and economic burden associated with asthma and
      the disease continues to be underdiagnosed and undertreated. In this study the
      AQLQ-M was administered to 826 asthmatic patients from continental Portugal
      (97.9% Caucasian, mean age 40.5 years, 30.2% male, 69.8% female), followed up by
      pulmonologists and allergologists. Patients were classified in line with the
      Global Initiative for Asthma (GINA) severity categories: 40.5% intermittent
      asthma, 26.9% mild persistent, 21.4% moderate persistent, 11.2% severe
      persistent. AQLQ-M scores maintained significant relationships with asthma
      severity, symptoms and lung function. Most of the patients were not managed and
      74.6% were observed in an emergency room during last year. Women reported poorer
      QoL than men in all the questionnaire's subscales. Surprisingly, smokers
      presented better QoL than non-smokers. The results of this study evidence that
      the Portuguese version of the AQLQ-M is a useful instrument for measuring health
      related quality of life in adults with asthma.

PMID- 18622526
TI  - Indoor air quality and respiratory symptoms in Porto schools.
AB  - AIM: To evaluate the association between the indoor air quality in Porto schools
      and the prevalence of allergic and respiratory symptoms in adolescents. MATERIAL
      AND METHODS: Temperature, relative humidity, carbon dioxide (CO2) and volatile
      organic compound (VOC) concentrations were evaluated in nine Porto schools.
      Questionnaires were distributed to 9 classes of 7th , 8th and 9th year students
      in each school, total 1607 adolescents, with a mean age of 14.0 years (standard
      deviation=0.3). Information was collected on participants' socio-demographic and
      social characteristics, behaviour, and housing conditions. The International
      Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to
      evaluate respiratory symptoms. RESULTS: 5.8% of participants stated they had had
      asthma, 9.2% wheezing, 22.0% sneezing and 6.6% itchy rash In the 12 months
      preceding the evaluation. After adjustment for parental educational attainment
      level, CO2 > 2100 ppm values were associated with exercise- induced wheeze
      [OR=1.86 (95%CI:1.20-2.89)] and night cough [OR=1.40 (4.20-2.89)]. We observed an
      increasing odds ratio in wheezing symptoms over the last 12 months, in asthma 'at
      some point' and asthma over the last 12 months, and night cough at schools with
      higher VOC values. The association was not statistically significant, however.
      CONCLUSION: Lower indicators of indoor air quality, particularly CO2, were
      associated with a greater respiratory symptomatology.

PMID- 18622527
TI  - [Strategical use of genotyping of Mycobacterium tuberculosis in tuberculosis
      control].
AB  - The tuberculosis situation in Portugal justifies the use of a strategy for the
      genotyping of Mycobacterium tuberculosis, particularly as Portugal is part of the
      global backdrop of human mobility, something which has a knock-on effect on the
      pandemic. Several international studies have placed spoligotyping and MIRU- VNTR
      typing as first line techniques for the molecular epidemiology of Mycobacterium
      tuberculosis as these techniques rely on simple technologies (PCR) and produce
      patterns which are easily translated into a direct interpretation numerical code.
      Spoligotyping has been accordingly proposed for all the isolates, while MIRU-VNTR
      typing should be applied to isolates with a common spoliotype. Other techniques,
      including IS6110-RFLP, should be reserved for use ill accordance with selected
      criteria. Previous studies in Portugal using spoligotyping have underlined the
      advantages of a strategy based on sampling consecutive patient isolates with no
      prior selection criteria. This allows characterisation of the M. tuberculosis
      population structure through monitoring the distribution of the genotypes
      geographically over time and within the various risk groups. On the other hand,
      the association of spoligotyping, MIRU-VNTF (typing and, possibly, other
      techniques, needs evaluating as part of bigger pictures, including identifying
      recent transmission situations, distinguishing between reinfection and relapse
      episodes and mapping the size and dynamics of disease transmission. The solution
      to the tuberculosis problem in Portugal implies structuring genotyping's role in
      tuberculosis prevention and control and its evaluation through concrete examples
      and results.

PMID- 18622528
TI  - [Cough in paediatrics].
AB  - Cough is perhaps the most frequently seen symptom in children and as such one of
      the most common reasons for physician appointments. The mechanics and causes of
      cough in children are different to those in adults and imply a different
      diagnostic and therapeutic management. This article reviews the physiopathology
      of cough in children, the most frequent causes, the initial evaluation and the
      treatment slant.

PMID- 18622529
TI  - [Tracheal tumors review--a clinical case of adenoid cystic carcinoma].
AB  - Tracheal tumours are rare, accounting for only about 0.3% of all bodily tumours.
      Their incidence is less than 0.2 per 100 000 inhabitants and 180 times less
      frequent than lung cancer. The reason for their rarity is not so clear. It is
      possible that turbulent airflow in the trachea protects its mucosa from inhaled
      carcinogen deposits. The authors report a case of adenoid cystic carcinoma in a
      23 year-old woman, non-smoker, with acute clinical inspiratory stridor, where Nd
      Yag laser use was extremely important to tracheal permeability as the tumor
      occupied over 80% of the tracheal lumen and could have led to imminent patient
      asphyxia.

PMID- 18622530
TI  - [Primary pleomorphic sarcoma of the lung].
AB  - The World Health Organization (WHO) classification of lung cancers ranks the
      heterogeneous nonsmall cell lung cancer (N-SCLC) group, encompassing sarcoma or
      sarcoma-containing tumours under one heading: "carcinomas with pleomorphic,
      sarcomatoid or sarcomatous elements". This group contains entities such as
      pleomorphic carcinoma (PC), spindle cell carcinoma (SCC), giant cell carcinoma
      (GCC), carcinosarcoma (CS) and pulmonary blastoma (PB). These tumors are rare
      overall, making up approx. 0.1-0.4% of all lung malignancies. They are more
      commonly found in males who are heavy smokers, diagnosed at the age of 60 on
      average and follow an aggressive clinical course. The authors describe the case
      of a male patient with primary pleomorphic lung sarcoma and also include a review
      of the literature.

PMID- 18622531
TI  - Primary tracheobronchial amyloidosis--two case reports.
AB  - Primary tracheobronchial amyloidosis is a form of respiratory amyloidosis,
      characterised by insoluble amyloid fibril proteins deposits along the airways
      wall. It is an uncommon disease, requiring a tissue sample to establish the
      definite diagnosis based on specific pathological features. The authors report
      two cases of tracheobronchial amyloidosis, describing their symptoms and the
      diagnostic and therapeutic procedures that were performed.

PMID- 18622532
TI  - [Lipoid pneumonia].
AB  - Lipoid pneumonia (LP) is a pneumonitis resulting from the aspiration of lipids,
      and is commonly associated with the use of mineral oil as a laxative. LP is
      relatively unfamiliar to clinicians and is probably underdiagnosed. Making a
      diagnosis of LP requires a high degree of clinical suspicion. The aim of this
      publication are to present a case of a patient with LP and to increase physician
      awareness of LP, its diagnosis and prevention.

PMID- 18622533
TI  - [Idiopathic chronic eosinophilic pneumonia--a clinical case report].
AB  - The eosinophilic pneumonias are a heterogeneous group of pulmonary disorders,
      which may compromise only the air ways, the pulmonary parenchyma, or both,
      characterised by alveolar eosinophils and infiltration of pulmonary tissue, with
      or without peripheral blood eosinophilia. Idiopathic Chronic Eosinophilic
      Pneumonia (ICEP), detailed description was by Carrington in 1969, is a rare
      eosinophilic lung disease, of unknown aetiology, characterised by peripheral
      blood eosinophilia, chest radiograph infiltrates and prompt response to
      corticosteroid therapy. ICEP most commonly affects women of middle age and usual
      symptoms are cough, dyspnea, fever and weight loss. The authors present a case of
      ICEP in a young woman, 21 years old, non-smoker and previously healthy.

PMID- 18622534
TI  - [Disseminated tuberculosis--a case report and discussion].
AB  - The authors report the case of a 13 year-old boy with disseminated tuberculosis
      evidenced by bilateral otomastoiditis associated to abdominal pain, ascites and
      apical alveolar pneumonia, prior history of contact with tuberculosis (TB)
      patients and radiology findings at mastoiditis, abdominal tract and thorax.
      Diagnosis was confirmed through positive culture for Mycobacterium tuberculosis
      from mastoiditis surgical drainage. After 6 months of anti-tuberculosis treatment
      there was remission of symptoms and regression of radiology findings.

PMID- 18622535
TI  - [The mild traumatic brain injury - a simple theme?].

PMID- 18622538
TI  - Laparoscopic Heller myotomy using hook electrocautery: a safe, simple, and
      inexpensive alternative.
AB  - BACKGROUND: Laparoscopic Heller myotomy (LHM) currently is considered the
      standard surgical therapy for achalasia. Historically, LHM has been associated
      with an intraoperative esophageal perforation rate of 5% to 10%. Recent
      literature has suggested that robotically assisted Heller myotomy is safer due to
      a reported lower incidence of intraoperative esophageal perforation than with
      conventional techniques. This study evaluated the results of LHM in a large
      series using simple hook electrocautery. METHODS: All patients undergoing LHM
      with Dor fundoplication (LHMDF) for achalasia by a single surgeon (A.D.P.) from
      2003 through 2006 were reviewed retrospectively at a multicenter academic
      institution. Demographic, perioperative, and follow-up data were collected.
      RESULTS: A total of 54 patients (52% female and 48% male) underwent LHMDF for the
      treatment of achalasia. The average age of these patients was 50 years, although
      6 patients were younger than 18 years. The average body mass index (BMI) was
      26.7, although four patients had a BMI exceeding 35. The average operative time
      was 113 min, and the estimated blood loss was 23 ml. The average length of
      hospital stay was 34 h. Only one patient (1.9%) underwent conversion to an open
      procedure, because of inadequate exposure attributed to an enlarged liver. One
      intraoperative esophageal perforation (1.9%) occurred in the series, which was
      sutured during the original operation without sequelae. Preoperatively, Botox
      injection therapy was administered for 24% of the patients and endoscopic
      dilation for 43%. Despite evidence that preoperative Botox increases the risk of
      esophageal perforation, this was not demonstrated in the patient population of
      this study. No postoperative leaks occurred, and only 3.7% of the patients had
      persistent dysphagia during an average follow-up period of 5 months. CONCLUSIONS:
      According to the findings, LHMDF using simple hook electrocautery is safe,
      inexpensive, and effective for the treatment of achalasia. The current series
      demonstrates that with meticulous surgical technique, intraoperative esophageal
      perforation is a rare event with this procedure. Hook electrocautery provides
      safety comparable with that of robotically assisted Heller myotomy, avoiding the
      added expense and operative time of a robotic system.

PMID- 18622537
TI  - Acculturation, psychiatric comorbidity and posttraumatic stress disorder in a
      Taiwanese aboriginal population.
AB  - BACKGROUND: This study investigates acculturation and other antecedent
      psychiatric and socio-environmental risk factors for posttraumatic stress
      disorder (PTSD) in one aboriginal group (the Bunun) exposed to an earthquake
      disaster in Taiwan. METHOD: Respondents (n = 196) were assessed 5 months after
      the disaster, using a Chinese version of the Schedules for Clinical Assessment in
      Neuropsychiatry and the Taiwan Aboriginal Acculturation Scale. RESULT: Four risk
      factors exerted independent effect on the risk of PTSD, including magnitude of
      the earthquake, subsequent traumas, antecedent major depressive disorder and
      acculturation status. CONCLUSION: Public mental health programs need to consider
      the liability to PTSD in populations with different ethnicity and socio-cultural
      environments.

PMID- 18622539
TI  - Percutaneous transesophageal gastrostomy (PTEG): a safe and effective technique
      for gastrointestinal decompression in malignant obstruction and massive ascites.
AB  - BACKGROUND: Enteral feeding and gastric decompression devices are common in
      critical, terminal, and chronically ill patients. Percutaneous transesophageal
      gastrostomy (PTEG) is a nonsurgical technique that creates an esophagostomy and
      allows enteral access in patients with a hostile abdomen, altered gastric
      anatomy, massive ascites, and carcinomatosis. We review our indications,
      technical experience, complications, and short- and long-term quality of life
      (QOL) in patients that underwent the PTEG procedure. METHODS: Patients were
      terminally ill from advanced cancer requiring gastrointestinal decompression or
      had hostile abdomens needing long-term feeding access. The procedure is carried
      out by inserting a rupture-free balloon (RFB) into the cervical esophagus and
      utilizing transcutaneous ultrasound to puncture the balloon. A guide wire is
      passed through the needle into the balloon, followed by a dilator and sheath. The
      in-dwelling catheter is inserted through the sheath, which exits the esophagus,
      and resides in the stomach. Proper placement is confirmed by fluoroscopy.
      RESULTS: From December 2003 to January 2006, 17 patients were treated with PTEG.
      Except for two patients, all of the patients had advanced metastatic cancer.
      Presenting symptoms were nausea, vomiting, and dysphagia. Average age was 62.8
      years, with nine men. Placement was successful in 16 patients (94%). There were
      no major complications and three minor complications (17.6%). Minor complications
      included two esophageal leaks at the catheter site and one catheter dislodgement.
      Seven patients (41.2%) died within 1 month after the procedure from their
      preexisting medical conditions. All patients were capable of being discharged
      from the hospital with adequate enteral access and gastrointestinal
      decompression. CONCLUSIONS: PTEG is a safe and effective method of enteral
      feeding and decompression in patients that have contraindications to standard
      enteral access. Appropriate patient selection and timing of PTEG placement is
      crucial for optimum benefit.

PMID- 18622540
TI  - Results of a new method to stop acute bleeding from esophageal varices:
      implantation of a self-expanding stent.
AB  - BACKGROUND: Acute bleeding from nontreated esophageal varices is associated with
      a mortality rate of 30% to 50%. Various pharmacologic and interventional methods
      to stop acute bleeding are available. However, for 10% to 20% of patients,
      therapy fails to stop the bleeding. This study aimed to assess the SX-ELLA Stent
      Danis Set (which has a self-expanding metal stent) instead of a balloon probe for
      compression of esophageal varices. METHODS: Using a multidisciplinary approach, a
      self-expanding stent was placed in 39 patients between January 2003 and August
      2007. For 34 of these patients with ongoing bleeding from esophageal varices,
      stent implantation was performed with the SX-ELLA Stent Danis Set, and the
      patients were included in this study. For all these patients, common methods
      failed to stop hemorrhage. With the SX-ELLA Stent Danis Set, the stent was
      implanted with a positioning balloon that enabled delivery without X-ray control.
      After implantation of the stent, its position was controlled by endoscopy and
      computed tomography (CT) scan. RESULTS: For all 34 patients, the implantation of
      the esophageal stent succeeded in stopping ongoing bleeding. No stent-related
      complications occurred during or after stent implantation. No bleeding recurrence
      was observed during the stent implantation (median time, 5 days; range 1-14
      days). For all the patients, the stent could be extracted by endoscopy without
      any complications using an extractor. Nine patients died of hepatic failure
      within 30 days after the procedure. No rebleeding occurred. CONCLUSIONS: The use
      of a self-expanding stent to stop acute bleeding from esophageal varices is a new
      therapeutic method. The authors' initial experience, which involved no method
      related mortality or complications, is encouraging. More data are necessary to
      confirm their results.

PMID- 18622541
TI  - NOTES, the debate continues.

PMID- 18622542
TI  - Sexual function after suburethral sling removal for dyspareunia.
AB  - INTRODUCTION: Impact on sexual function has received little attention in the
      medical literature for a long time. Because of the site of insertion of permanent
      tension free vaginal tape (TVT) the G spot might be affected or the tape might
      interfere with arousal and sensory stimulation. Recent studies have reported
      varying degrees of sexual impairment after TVT insertion ranging from 0% to 15%
      including dyspareunia. AIM: The aim of this study was to evaluate sexual function
      before and after suburethral sling removal due to postoperative female de novo
      dyspareunia. As a secondary outcome, general patients' satisfaction with their
      overall continence situation was assessed. PATIENTS AND METHODS: Between December
      2005 and December 2007, we included 18 female patients who complained of de novo
      dyspareunia after suburethral sling insertion for urinary stress incontinence.
      All patients filled in an FSFI questionnaire prior to sling removal and at 3
      months postoperatively. Additionally, all women were asked to estimate their
      general satisfaction regarding their continence situation using a Visual Analogue
      Scale (VAS) from 0 to 10, with 0 being the least satisfying situation and 10
      being the most satisfying situation. All patients underwent gynaecological
      examination including ICS-pelvic organ prolapse staging (ICS-POP score). RESULTS:
      Of the 18 slings, ten were transobturator tapes (6 x TVT-O, 2 x Monarch, 2 x
      unknown) and eight were retropubic tapes (7 x TVT, 1 x SPARC). Desire, arousal,
      lubrication, satisfaction, and pain improved statistically significant. Orgasm
      scores were low with median scoring of 1.5 scores before and 1.0 scores after
      sling removal, and they did not change significantly after sling removal. The
      satisfaction rate deteriorated from a median of 7 (95% confidence interval [CI]
      6.3-7.7) to a median of 4 (95% CI 3.7-5.1; p=0.99) but not statistically
      significant. CONCLUSIONS: Sexual function in patients with de novo dyspareunia is
      likely to improve after sling removal but not in all domains. Bladder function
      may deteriorate.

PMID- 18622543
TI  - Influence of carbon dioxide pneumoperitoneum environment on adhesion and
      metastasis of a human ovarian cancer cell line.
AB  - BACKGROUND: This study aimed to explore the adhesion and metastasis capability of
      the human ovarian cancer cell line SKOV(3) after exposure to a simulated
      laparoscopic carbon dioxide (CO(2)) pneumoperitoneum environment and the related
      mechanism. METHODS: SKOV(3) was subjected to a simulated laparoscopic CO(2)
      pneumoperitoneum environment at various CO(2) pressures (8-12 mmHg) and exposure
      times (1-3 h). Cell adhesive capacity was determined by a mechanical method. Real
      time fluorescent quantitative polymerase chain reaction (FQ-PCR) and
      immunocytochemical staining were used to examine the mRNA and protein expressions
      of heparanase (HPSE) and vascular endothelial growth factor C (VEGF-C) in
      SKOV(3). Cells cultured in a standard environment were used as the control.
      RESULTS: The increase of SKOV(3) cell adhesion capability was associated with
      CO(2) pressure and exposure time. A significantly higher adhesion capability was
      observed in the group with exposure to 10 mmHg for 2 h over a 48 h period, as
      compared with the control groups (p < 0.05). The expressions of HPSE and VEGF-C
      in SKOV(3), which are closely related to metastasis capability, also increased.
      Significantly higher expressions were observed in the group with exposure to 10
      mmHg for 3 h over a 48 h period, as compared with the control groups (p < 0.01).
      CONCLUSIONS: The adhesion and metastasis capacity of SKOV(3) increased with
      overexpression of HPSE and VEGF-C and were positively related to CO(2) pressure,
      exposure, and culture time.

PMID- 18622544
TI  - Laparoscopically assisted bowel surgery in an era of double-balloon enteroscopy:
      from inside to outside.
AB  - BACKGROUND: This report describes an integrated therapeutic method of double
      balloon enteroscopy (DBE) and laparoscopically assisted bowel surgery (LABS) for
      small bowel diseases. METHODS: In this study, 34 patients with obscure
      gastrointestinal bleeding (OGIB, n=25) and abdominal pain (n=9) who underwent DBE
      and LABS were analyzed. Demographics, patient characteristics, diagnostic tests,
      DBE and LABS findings, surgical results, and long-term outcome were reviewed.
      RESULTS: All 34 patients underwent DBE without significant complications. Biopsy
      was performed for 16 patients, ink mark for 25 patients, and temporary
      homeostasis during DBE for 5 patients. Laparoscopically assisted bowel resection
      was performed for 27 patients, converted laparotomy for 6 patients, and
      laparoscopic diagnosis alone for 1 patient. The pathologic diagnoses included
      gastrointestinal stromal tumor (GIST) for eight patients, primary adenocarcinoma
      for three patients, lymphoma for three patients, Meckel's diverticulum for three
      patients, angiodysplasia for three patients, ulcer for two patients, lipoma for
      four patients, metastasis for three patients, jejunal diverticulosis for two
      patients, and tuberculosis ileitis, ileal varix, and lymphangioma for one patient
      each. No surgical mortalities or significant morbidities were noted. After a
      follow-up period of 14+/-3 months, 29 patients were well without disease
      recurrence. Two patients had symptomatic recurrence, and three patients died of
      cancerous progression. CONCLUSIONS: The combination of DBE and LABS represents an
      ideal therapeutic method, especially for OGIB caused by small bleeding neoplasms
      or vascular lesions.

PMID- 18622545
TI  - Reversal of Hartmann's procedure through the stomal side: a new even more minimal
      invasive technique.
AB  - BACKGROUND: Several minimal invasive, mainly laparoscopic-assisted, techniques
      for reversal of Hartmann's procedure (HP) have been published. The purpose of
      this pilot study was to assess a minimal invasive procedure through the stomal
      site that may compare favorably with open or laparoscopic-assisted procedures in
      terms of operative time, hospital stay and postoperative complications. METHODS:
      HP reversal through the stomal side was attempted in 13 consecutive patients.
      Lysis of intra-abdominal adhesions was done manually through an incision at the
      formal stoma side, without direct vision between thumb and index finger. The
      rectal stump was identified intra-abdominally using a transanal rigid club. A
      manually controlled stapled end-to-end colorectal anastomosis was created.
      RESULTS: Mean duration of operation was 81 min (range 58-109 min); mean hospital
      stay was 4.2 days (range 2-7 days). In two patients the procedure was converted
      because of strong adhesions in the lower pelvic cavity around the rectal stump
      that could not be lysed manually safely. No complications occurred in the
      patients in whom reversal was completely done through the stomal site.
      CONCLUSIONS: In our opinion, restoration of intestinal continuity through the
      stomal side after HP is a feasible operation, without need for additional
      incisions. In the hands of a specialist gastrointestinal surgeon this technique
      can be attempted in all patients, as conversion to a laparoscopic-assisted or an
      open procedure can be performed when necessary.

PMID- 18622546
TI  - Laparoscopic repair of recurrent groin hernia: results of a prospective study.
AB  - BACKGROUND: Recurrences continue to be seen after repair of inguinal hernias. The
      repair of these recurrent hernias is a more complex and demanding procedure, with
      a high re-recurrence rate. Definite advantage has been demonstrated with
      endoscopic repair of these hernias. METHODS: The results for this prospective
      study from January 2003 to December 2006 were evaluated after laparoscopic repair
      of 65 recurrent hernias in 61 patients. The patients were followed up for 1 year.
      Longer follow-up evaluation was performed for the patients who underwent surgery
      in the initial 3 years. RESULTS: In this study, 37 recurrent hernias were managed
      using the transabdominal preperitoneal technique (TAPP) technique and 28 using
      the totally extraperitoneal (TEP) technique. There was no conversion and no cases
      of postoperative wound infection. Of the 12 metachronous hernias repaired
      simultaneously, 3 were occult. Seroma developed in five patients. At a follow-up
      assessment after 1 year, one patient had groin pain, and there was one re
      recurrence. A longer follow-up period with a mean of 35.11 months failed to show
      any new re-recurrence. CONCLUSIONS: Laparoscopic repair of recurrent inguinal
      hernia is safe and effective. The morbidity and recurrence rates for the
      procedure are as low as for laparoscopic repair of primary hernias. Laparoscopic
      repair should be the gold standard for these hernias.

PMID- 18622547
TI  - Performance of basic manipulation and intracorporeal suturing tasks in a robotic
      surgical system: single- versus dual-monitor views.
AB  - BACKGROUND: Technical advances in the application of laparoscopic and robotic
      surgical systems have improved platform usability. The authors hypothesized that
      using two monitors instead of one would lead to faster performance with fewer
      errors. METHODS: All tasks were performed using a surgical robot in a training
      box. One of the monitors was a standard camera with two preset zoom levels
      (zoomed in and zoomed out, single-monitor condition). The second monitor provided
      a static panoramic view of the whole surgical field. The standard camera was
      static at the zoomed-in level for the dual-monitor condition of the study. The
      study had two groups of participants: 4 surgeons proficient in both robotic and
      advanced laparoscopic skills and 10 lay persons (nonsurgeons) who were given
      adequate time to train and familiarize themselves with the equipment. Running a
      50-cm rope was the basic task. Advanced tasks included running a suture through
      predetermined points and intracorporeal knot tying with 3-0 silk. Trial
      completion times and errors, categorized into three groups (orientation,
      precision, and task), were recorded. RESULTS: The trial completion times for all
      the tasks, basic and advanced, in the two groups were not significantly
      different. Fewer orientation errors occurred in the nonsurgeon group during knot
      tying (p=0.03) and in both groups during suturing (p=0.0002) in the dual-monitor
      arm of the study. Differences in precision and task error were not significant.
      CONCLUSIONS: Using two camera views helps both surgeons and lay persons perform
      complex tasks with fewer errors. These results may be due to better awareness of
      the surgical field with regard to the location of the instruments, leading to
      better field orientation. This display setup has potential for use in complex
      minimally invasive surgeries such as esophagectomy and gastric bypass. This
      technique also would be applicable to open microsurgery.

PMID- 18622548
TI  - Psychomotor performance measured in a virtual environment correlates with
      technical skills in the operating room.
AB  - BACKGROUND: This study was conducted to validate the role of virtual reality
      computer simulation as an objective method for assessing laparoscopic technical
      skills. The authors aimed to investigate whether performance in the operating
      room, assessed using a modified Objective Structured Assessment of Technical
      Skill (OSATS), correlated with the performance parameters registered by a virtual
      reality laparoscopic trainer (LapSim). METHODS: The study enrolled 10 surgical
      residents (3 females) with a median of 5.5 years (range, 2-6 years) since
      graduation who had similar limited experience in laparoscopic surgery (median, 5;
      range, 1-16 laparoscopic cholecystectomies). All the participants performed three
      repetitions of seven basic skills tasks on the LapSim laparoscopic trainer and
      one laparoscopic cholecystectomy in the operating room. The operating room
      procedure was video recorded and blindly assessed by two independent observers
      using a modified OSATS rating scale. Assessment in the operating room was based
      on three parameters: time used, error score, and economy of motion score. During
      the tasks on the LapSim, time, error (tissue damage and millimeters of tissue
      damage [tasks 2-6], error score [incomplete target areas, badly placed clips, and
      dropped clips [task 7]), and economy of movement parameters (path length and
      angular path) were registered. The correlation between time, economy, and error
      parameters during the simulated tasks and the operating room procedure was
      statistically assessed using Spearman's test. RESULTS: Significant correlations
      were demonstrated between the time used to complete the operating room procedure
      and time used for task 7 (r (s) = 0.74; p = 0.015). The error score demonstrated
      during the laparoscopic cholecystectomy correlated well with the tissue damage in
      three of the seven tasks (p < 0.05), the millimeters of tissue damage during two
      of the tasks, and the error score in task 7 (r (s) = 0.67; p = 0.034).
      Furthermore, statistically significant correlations were observed between the
      economy of motion score from the operative procedure and LapSim's economy
      parameters (path length and angular path in six of the tasks) (p < 0.05).
      CONCLUSIONS: The current study demonstrated significant correlations between
      operative performance in the operating room (assessed using a well-validated
      rating scale) and psychomotor performance in virtual environment assessed by a
      computer simulator. This provides strong evidence for the validity of the
      simulator system as an objective tool for assessing laparoscopic skills. Virtual
      reality simulation can be used in practice to assess technical skills relevant
      for minimally invasive surgery.

PMID- 18622549
TI  - Ergonomic assessment of neck posture in the minimally invasive surgery suite
      during laparoscopic cholecystectomy.
AB  - BACKGROUND: With the expanding implementation of minimally invasive surgery, the
      operating team is confronted with challenges in the field of ergonomics. Visual
      feedback is derived from a monitor placed outside the operating field. This
      crossover trial was conducted to evaluate and compare neck posture in relation to
      monitor position in a dedicated minimally invasive surgery (MIS) suite and a
      conventional operating room. METHODS: Assessment of the neck was conducted for 16
      surgeons, assisting surgeons, and scrub nurses performing a laparoscopic
      cholecystectomy in both types of operating room. Flexion and rotation of the
      cervical spine were measured intraoperatively using a video analysis system. A
      two-question visual analog scale (VAS) questionnaire was used to evaluate posture
      in relation to the monitor position. RESULTS: Neck rotation was significantly
      reduced in the MIS suite for the surgeon (p = 0.018) and the assisting surgeon (p
      < 0.001). Neck flexion was significantly improved in the MIS suite for the
      surgeon (p < 0.001) and the scrub nurse (p = 0.018). On the questionnaire, the
      operating room team scored their posture significantly higher in the MIS suite
      and also indicated fewer musculoskeletal complaints. CONCLUSIONS: The ergonomic
      quality of the neck posture is significantly improved in the MIS suite for the
      entire operating room team.

PMID- 18622550
TI  - Molecular mechanisms underlying postoperative peritoneal tumor dissemination may
      differ between a laparotomy and carbon dioxide pneumoperitoneum: a syngeneic
      mouse model with controlled respiratory support.
AB  - BACKGROUND: The mechanisms promoting postoperative peritoneal tumor dissemination
      are unclear. This study aimed to investigate postoperative tumor dissemination
      over time on both tissue and molecular levels. METHODS: For this study, C57BL6
      mice were randomized into four groups: anesthesia alone (control), carbon dioxide
      (CO(2)) pneumoperitoneum at low (2 mmHg) or high (8 mmHg) intraperitoneal
      pressure (IPP), and laparotomy. A mouse ovarian cancer cell line (ID8) was
      injected intraperitoneally just before surgery. The groups were further
      subdivided into three groups, and a laparotomy was performed to evaluate tumor
      dissemination on postoperative day (POD) 7, 14, or 42. RESULTS: The incidence of
      cancer cell invasion into the muscle layers of the abdominal wall was
      significantly higher in the laparotomy and high-IPP groups than in the low-IPP
      and control groups on PODs 7 and 42. Expression levels of beta 1 integrin, cMet,
      urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator
      receptor (uPAR), and type-1 plasminogen activator inhibitor (PAI-1) mRNA in the
      disseminated nodules were not significantly different among the four groups on
      POD 7. However, the expression levels of all these genes in the disseminated
      nodules in the laparotomy group were significantly higher on POD 14 than on POD
      7. They then returned to control levels on POD 42. There were no significant
      differences in the expression levels of any of these genes among the groups on
      POD 42. CONCLUSIONS: The current study suggests that the molecular mechanisms
      underlying postoperative peritoneal tumor dissemination may differ between a
      laparotomy and CO(2) pneumoperitoneum. Therefore, strategies targeting
      postoperative tumor dissemination likely will need to account for the surgical
      environment.

PMID- 18622551
TI  - Randomized controlled trial investigating the effect of music on the virtual
      reality laparoscopic learning performance of novice surgeons.
AB  - BACKGROUND: Findings have shown that music affects cognitive performance, but
      little is known about its influence on surgical performance. The hypothesis of
      this randomized controlled trial was that arousing (activating) music has a
      beneficial effect on the surgical performance of novice surgeons in the setting
      of a laparoscopic virtual reality task. METHODS: For this study, 45 junior
      surgeons with no previous laparoscopic experience were randomly assigned to three
      equal groups. Group 1 listened to activating music; group 2 listened to
      deactivating music; and group 3 had no music (control) while each participant
      solved a surgical task five times on a virtual laparoscopic simulator. The
      assessed global task score, the total task time, the instrument travel distances,
      and the surgeons' heart rate were assessed. RESULTS: All surgical performance
      parameters improved significantly with experience (task repetition). The global
      score showed a trend for a between-groups difference, suggesting that the group
      listening to activating music had the worst performance. This observation was
      supported by a significant between-groups difference for the first trial but not
      subsequent trials (activating music, 35 points; deactivating music, 66 points; no
      music, 91 points; p = 0.002). The global score (p = 0.056) and total task time (p
      = 0.065) showed a trend toward improvement when participants considered the music
      pleasant rather than unpleasant. CONCLUSIONS: Music in the operating theater may
      have a distracting effect on novice surgeons performing new tasks. Surgical
      trainers should consider categorically switching off music during teaching
      procedures.

PMID- 18622552
TI  - Comparison of early outcomes for laparoscopic ventral hernia repair between
      nonobese and morbidly obese patient populations.
AB  - BACKGROUND: Obesity predisposes to incisional herniation and increased the
      incidence of recurrence after conventional open repair. Only sparse data on the
      safety and security of laparoscopic ventral hernia repair (LVHR) for morbidly
      obese patients are available. This study compared the incidence of perioperative
      complications and early recurrence after LVHR between morbidly obese and non
      morbidly obese patients. METHODS: The case records of consecutive patients who
      underwent LVHR between December 2002 and August 2007 were reviewed. Patients with
      a body mass index (BMI) lower than 35 kg/m2 were compared with morbidly obesity
      patients who had a BMI of 35 kg/m2 or higher. RESULTS: The study included 168
      patients (87 men) with a median age of 55 years (range, 24-92 years). Two
      conversions to open repair (1.2%) were performed, both for non-morbidly obese
      patients. Of the 168 patients, 42 (25%) were morbidly obese (BMI range, 35.0-58.0
      kg/m2) and 126 (75%) were non-morbidly obese (BMI range, 15.5-34.9 kg/m2). The
      groups showed no significant differences in age, gender, number or size of
      fascial defects, operative time, length of hospital stay, or incidence of
      perioperative complications. At a median follow-up period of 19 months (range, 6
      62 months), 20 patients (12%) had recurrent hernias. The incidence of recurrence
      was significantly associated with the size of the fascial defect and the size of
      the mesh, but not with morbid obesity. CONCLUSION: No significant difference in
      the incidence of perioperative complications or recurrence after LVHR was
      observed between the morbidly obese patients and the non-morbidly obese patients.

PMID- 18622553
TI  - Over-the-catheter precut to gain access to the biliary duct during ERCP
      rendezvous.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) rendezvous
      during laparoscopic cholecystectomy is an efficient and safe method to treat
      cholecystocholedocholithiasis. Advancing a guidewire through the cystic duct into
      the duodenum and withdrawing it in the accessory channel of duodenoscope may be,
      however, laborious. Moreover, rendezvous performed in the typical manner needs
      the use of several costly accessories. We herein describe a simpler and cheaper
      method to gain access to the biliary duct at rendezvous. METHODS: Twenty-four
      consecutive patients undergoing ERCP rendezvous during laparoscopic
      cholecystectomy were considered. A catheter was introduced in the cystic duct and
      advanced into the duodenum. Access to the bile duct was than achieved by means of
      a precut sphincterotomy performed over the catheter emerging from the papilla.
      RESULTS: Cannulation was successful in all but two patients, in whom ERCP was
      performed in the conventional manner. The only complication was a case of mild
      post-sphincterotomy bleeding. In comparison with the typical rendezvous technique
      our procedure allowed savings of about <euro>250, since its performance only
      requires a catheter and a knife sphincterotome. CONCLUSIONS: Over-the-catheter
      precut during ERCP rendezvous is a feasible and safe method which avoids the need
      for the manipulation of several accessories and guidewires, and thus results in
      money and time savings.

PMID- 18622554
TI  - Accuracy of endorectal ultrasonography in staging locally advanced rectal cancer
      after preoperative chemoradiation.
AB  - AIM: The aim of our study was to determine the accuracy of endorectal
      ultrasonography (ERUS) in staging locally advanced rectal cancer after
      preoperative neoadjuvant chemoradiation and to point out the most common reasons
      for false interpretation. METHODS: Forty-four patients with locally advanced
      rectal cancer received neoadjuvant chemoradiation followed by radical surgery.
      Restaging was done 1-2 weeks before surgery and the results of ERUS staging were
      compared with histopathology findings of the resected specimen. RESULTS: The
      accuracy of ERUS for T stage after chemoradiation was 75% (33/44). Overstaging
      occurred in 18% (8/44) of patients, and 7% (3/44) were understaged. The majority
      of overstaging occurred in patients with ERUS T3 tumors, eventually found to have
      pathological pT0-pT2 staging. Five patients (11.4%) had complete histology
      regression and only one of these patients was staged correctly while others were
      overstaged. In the detection of perirectal lymph node metastases, ERUS was
      accurate in 68% of patients (30/44). Twenty percent (9/44) of patients were
      overstaged and 11% were (5/44) understaged. CONCLUSIONS: ERUS provides a good
      accuracy rate for staging rectal cancer after neoadjuvant chemoradiation.
      However, it is insufficient in detection of complete pathological response.

PMID- 18622555
TI  - Very long-term outcomes of video-assisted thoracoscopic surgery for lung cancer.
AB  - BACKGROUND: The most critical parameter in the evaluation of the feasibility of
      video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer is long
      term outcome. In this study, patients in whom more than 5 years had elapsed since
      they had undergone VATS lobectomy for lung cancer were identified, and the 5-year
      survival rate and frequency of recurrence were evaluated as the long-term
      outcomes; in addition, the frequency of perioperative complications were also
      evaluated as the short-term outcomes. METHODS: The stage, histology,
      perioperative complications, recurrence, and survival data were carefully
      reviewed in 198 patients who underwent VATS lobectomy for lung cancer between
      1998 and 2002. RESULTS: Median postoperative follow-up period was 72.1 months. Of
      the 198 patients, 138 and 30 were diagnosed as having p-stage IA and IB disease,
      respectively, while the remaining 30 patients had more advanced disease.
      Perioperative complications were observed in 20 patients (10.1%), however, there
      were no perioperative mortalities. Recurrence was observed in 26 patients
      (13.1%): of these, 11 patients showed local recurrence, including malignant
      pleural effusion and mediastinal lymph node recurrence, and 16 patients showed
      distant metastasis, the lung being the commonest site of metastasis; six patients
      had both local recurrence and distant metastasis. During the study period, there
      were 26 deaths (13.1%), of which 17 were due to lung cancer and 9 were due to
      other causes. The 5-year overall survival rates of the patients with p-stage IA
      and IB disease were 93.5% and 81.6%, respectively. CONCLUSION: VATS lobectomy for
      the treatment of lung cancer is as feasible and safe as open lobectomy in terms
      of both very long- and short-term outcomes.

PMID- 18622556
TI  - Technique for transesophageal endoscopic cardiomyotomy (Heller myotomy): video
      presentation at the Society of American Gastrointestinal and Endoscopic Surgeons
      (SAGES) 2008, Philadelphia, PA.
AB  - BACKGROUND: Previous investigators have shown the feasibility of performing an
      esophageal myotomy using natural orifice translumenal endoscopic surgery (NOTES),
      but have been unsuccessful at extending the myotomy onto the body of the stomach.
      METHODS: In a nonsurvival porcine model, the authors used the self-approximating
      translumenal access technique (STAT) to create a submucosal tunnel in the upper
      esophagus and to extend it onto the body of the stomach allowing a complete
      cardiomyotomy. RESULTS: The STAT approach was successfully used to create a
      submucosal tunnel and perform a complete myotomy of the gastroesophageal junction
      without complication. CONCLUSIONS: A complete Heller-type cardiomyotomy can be
      successfully performed using transesophegeal NOTES.

PMID- 18622557
TI  - The safety and efficacy in humans of endoscopic mucosal resection with
      hydroxypropyl methylcellulose as compared with normal saline.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) is a therapeutic
      modality that utilizes fluid to form a submucosal fluid cushion (SFC) for the
      treatment of early gastrointestinal neoplasia. The goal of this study was to
      determine the safety and efficacy in humans of EMR with hydroxypropyl
      methylcellulose (HPMC) as compared with historical controls of EMR performed with
      normal saline. PATIENTS AND METHODS: A retrospective cohort study presented data
      on EMR performed in 89 lesions in 88 patients was compared with 22 control EMRs
      performed with normal saline. Indications for EMR included known or suspected
      cancerous or precancerous lesions of the gastrointestinal tract. Efficacy of EMR
      was based on rates of complete excision and tumor recurrence. RESULTS: EMR was
      performed in 89 lesions with HPMC-EMR used in 67 lesions and compared with 22
      historical control lesions treated with saline EMR by the same five endoscopists.
      Lesion size and location were similar in both HPMC and saline groups.
      Complications were observed in six patients [5/67 (8%) HPMC and 1/22 (5%) saline,
      p > 0.2]. Long-term follow-up with repeat endoscopy was available on 43 lesions
      and identified 35/43 to be completely excised [20/25 (80%) HPMC-EMR and 15/18
      (83%) saline EMR, p > 0.2]. Size of the lesion was not associated with success.
      CONCLUSION: Both HPMC and normal saline are effective agents for creating a
      submucosal cushion for EMR. Larger randomized studies are needed to determine
      statistically significant differences in efficacy.

PMID- 18622558
TI  - The effect of extended post-discharge chemical thromboprophylaxis on venous
      thromboembolism rates after bariatric surgery: a prospective comparison trial.
AB  - BACKGROUND: The effect of extended post-discharge thromboprophylaxis (ETP) on
      venous thromboembolism (VTE) rates following bariatric surgery (BS) is unknown.
      METHODS: 308 consecutive patients who underwent BS between 2003 and 2007 and who
      had > 1 month of follow-up were included. In-hospital-only VTE prophylaxis (group
      A), or extended 10-day ETP (group B) was used in 132 and 176 patients,
      respectively. All patients underwent bilateral lower extremity venous Doppler
      studies (BLEVDS) prior to discharge. Primary endpoint was the incidence of VTE
      within 30 days postoperatively. VTE was defined as a clinically evident deep vein
      thrombosis or pulmonary embolism documented by positive BLEVDS, or computed chest
      tomography. The primary safety endpoint was bleeding associated with > or = 2
      g/dL decrease in hemoglobin compared with baseline, transfusion or reoperation.
      RESULTS: The incidence of VTE was 1.9% (6/308); 66.6% (4/6) of cases occurred
      after cessation of thromboprophylaxis. There were no deaths in either group. With
      the exception of percentage open surgical approach (A: 3% versus B: 0%, p =
      0.03), percentage conversions (A: 0 versus B: 3.8%, p = 0.01), and hospital stay
      (A: 3 versus B: 2.2 days, p < 0.0001), the two groups were comparable in relation
      to age, sex, body mass index, percentage revision surgery, operative time, and
      history of VTE. VTE rate was significantly higher in group A (A: 4.5% versus B:
      0%, p = 0.006). Although morbidity was higher in group A (A: 12.1% versus B:
      1.1%, p < 0.0001), no VTE event occurred in patients who had other complications.
      The incidence of significant bleeding was lower in group B (A: 5.3% versus B:
      0.56%, p = 0.02). CONCLUSIONS: ETP is safe and effective in reducing the
      incidence of VTE as compared with in-hospital thromboprophylaxis only.

PMID- 18622559
TI  - Two-center experience in the treatment of hemorrhoidal disease using Doppler
      guided hemorrhoidal artery ligation: functional results after 1-year follow-up.
AB  - INTRODUCTION: Doppler-guided hemorrhoidal artery ligation (DGHAL), as a method of
      treating hemorrhoidal disease, is currently used in many centers across Europe,
      Asia, and Australia. The aim of our study was to evaluate the clinical
      effectiveness and functional results of DGHAL as estimated by means of anorectal
      manometry. MATERIALS AND METHODS: Between 2000 and 2006 the DGHAL procedure was
      performed on 507 patients with II-IV degree hemorrhoids in two centers (Poland
      and Austria). Three hundred eight patients were included in the initial phase of
      the study, designed to estimate the method's effectiveness. During the second
      phase (199 patients) selected functional results were also assessed. Patients
      were classified as having grade II (144), III (319), and IV (44) hemorrhoids.
      RESULTS: There were no intra- and immediate postoperative complications. Good
      results were reported by 351 patients (69.2%), and were acceptable in a further
      75 cases (4.8%). When the patients were grouped according to the stage of
      hemorrhoidal disease, 133 out of 144 patients (92.4%) with grade II and 272 out
      of 324 (84%) with grade III had very good or good results. Only 18 out of 44
      patients (41%) with grade IV were satisfied with the operation. Fifty-nine
      patients after anorectal folds, fissure or anal canal polyp excision required
      analgesics for 1-2 days. Apart from lower contraction amplitude and contraction
      speed after 1 month there were no differences in anorectal functional tests.
      CONCLUSION: Based on our results we may conclude that DGHAL is a safe and
      effective method and may offer an important alternative to operative
      hemorrhoidectomy with no risk of postoperative stool incontinence, minimal
      postoperative pain, and early return of patients to their normal activities.
      Nevertheless, this is a fairly new procedure with a short-term follow-up. Until 5
      year observations of large, multicenter, randomized trials are published we
      cannot recommend this method as a gold-standard procedure, although it still can
      offer significant benefits to patients.

PMID- 18622560
TI  - Laparoscopic surgery for rectal cancer: oncological results and clinical outcome
      of 225 patients.
AB  - INTRODUCTION: The efficacy and feasibility of laparoscopic resection for rectal
      cancer has been proved, but the results of prospective, randomized studies are
      not yet available. Here we present a prospective observational study evaluating
      oncological and clinical outcome after laparoscopic surgery in patients with
      rectal cancer. PATIENTS AND METHODS: Between January 1998 and March 2005, 225
      patients with rectal adenocarcinoma underwent laparoscopic surgery at the
      University of Regensburg Medical Center. Clinical and oncological outcome of
      these patients including perioperative and long-term complications was evaluated.
      Survival curves were calculated according to the Kaplan-Meier method. Minimum
      follow-up was 24 months. RESULTS: The distribution of the International Union
      against Cancer (UICC) stages was: 37.7% stage I, 20.5% stage II, 24.9% stage III,
      and 16.9% stage IV. Local recurrence was diagnosed in 5.8% and distant metastases
      in 8.1% of cases after mean follow-up of 36.4 months. The 5-year overall survival
      rate was 75.7% after curative and 40.7% after palliative surgery (p<0.05). The
      stage-related survival rates were 86.7% for UICC stage I, 61.7% for stage II,
      68.1% for stage III, and 40.1% for stage IV. CONCLUSIONS: Our results demonstrate
      the efficacy and technical feasibility of laparoscopic surgery for rectal cancer
      regarding the perioperative morbidity and the oncological outcome.

PMID- 18622561
TI  - Laparoscopic liver resection: preliminary results from a UK centre.
AB  - BACKGROUND AND AIMS: Advancements in surgical technique and technology have
      facilitated safe laparoscopic liver resection in selected patients. The aim of
      this study is to evaluate the feasibility and outcome of laparoscopic liver
      resection. METHODS: Patients with lesions situated in the anterior and left
      lateral segments were selected for laparoscopic resection. Data were collected
      prospectively. RESULTS: Between 2003 and 2007, 24 patients (12 males) with a
      median (range) age of 65 (30-83) years underwent 24 laparoscopic hepatic
      resections for presumed colorectal metastases (n=20) and other indications (n=4).
      The resections included left hepatic lobectomy (n=14), other resections of two or
      three segments with or without metastasectomy (n=5), left hemihepatectomy (n=2)
      and unisegmentectomy (n=3). All procedures were completed laparoscopically.
      Median operating time was 155 min. Estimated median (range) blood loss was 100
      (25-1100) ml and one patient received two units blood transfusion. The operative
      morbidity rate was 4%, and there were no operative deaths. The median (range)
      postoperative hospital stay was 3 (1-14) days. At median (range) follow-up of
      13.5 (5-36) months, 4 patients (21%) had disease recurrence and 17 patients (89%)
      remained alive. CONCLUSIONS: In selected patients with lesions in the anterior
      and left lateral segments, laparoscopic liver resection is feasible, achieves
      adequate cancer resection and is associated with smooth and rapid recovery. Long
      term follow-up data are required for oncological results.

PMID- 18622562
TI  - Laparoscopic versus open liver resection of hepatic neoplasms: comparative
      analysis of short-term results.
AB  - BACKGROUND: Concerns have been raised regarding outcome after laparoscopic
      resection of hepatic neoplasms. This prospective study compared morbidity and
      adequacy of surgical margins in laparoscopic (LLR) versus open liver resection
      (OLR). METHODS: Outcome in 359 consecutive patients [male/female ratio 187/172;
      median age 60 years (range 18-84 years)] who underwent partial hepatectomy was
      analysed. Cirrhosis was present in 32 patients and preoperative chemotherapy was
      administered in 141 patients. Comparative analyses were performed using
      propensity scores for all and for matched patients (n=76 per group). RESULTS:
      Complications occurred in 68/250 (27.2%) patients after OLR and in 6/109 (5.5%)
      after LLR [odds ratio (OR) 0.16; 95% confidence interval (CI) 0.07-0.37;
      p<0.0001]. Median intraoperative blood loss was 500 ml (range 10-7,000 ml) in OLR
      and 100 ml (range 5-4,000 ml) in LLR (p<0.0001). Postoperative hospital stay was
      8 days (range 0-155 days) after OLR and 6 days (range 0-41 days) after LLR
      (p<0.0001). In patients treated for liver malignancy, the surgical resection
      margin was positive on histopathological examination in 5/237 after OLR and in
      1/77 after LLR. The magnitude of the resection margin was 7.5 mm (range 0-45 mm)
      in OLR and 10.0 mm (range 0-30 mm) in LLR (p=0.087). CONCLUSIONS: LLR for hepatic
      neoplasms seems to be noninferior to OLR regarding adequacy of surgical margins,
      and superior to OLR regarding short-term postoperative outcome.

PMID- 18622563
TI  - Laparoscopic liver resection without portal clamping: a prospective evaluation.
AB  - BACKGROUND: Previous comparative studies have demonstrated that laparoscopic
      liver resection is associated with more frequent use and longer duration of
      portal camping than open liver resection, a fact that may partially explain the
      improvement in operative blood loss reported by most series of laparoscopic liver
      resection. The aim of this prospective study was to evaluate the real need for
      portal clamping in laparoscopic liver surgery. STUDY DESIGN: Surgical outcomes of
      40 consecutive patients who underwent laparoscopic liver resection for benign and
      malignant lesions from September 2005 to August 2007 were evaluate. Portal
      clamping was not systematically used. RESULTS: No patient required blood
      transfusion and median blood loss was 160 ml (range 100-340 ml). Mean operating
      time was 267 min (range 220-370 min) and portal clamping was necessary in only
      one patient. Surgical complications included two grade I complication, three
      grade II, and one case of postoperative hemorrhage (grade III). CONCLUSIONS:
      Laparoscopic liver surgery without clamping can be performed safely with low
      blood loss.

PMID- 18622564
TI  - Primary closure of choledochotomy after emergency laparoscopic common bile duct
      exploration.
AB  - INTRODUCTION: The debate into whether or not to drain the common bile duct after
      laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis
      continues. Reports are in favour of primary closure of choledochotomy in elective
      setting. The aim of this study is to evaluate our experience in the primary
      closure of choledochotomy in emergency setting by analysing indications,
      operative time, hospital stay, complications, and outcome. METHODS: All patients
      undergoing LCBDE were prospectively entered into a database incorporating
      demographic and clinical data including mode of admission, indication for
      surgery, operation details and clinical outcome. All operations were performed by
      the same consultant (A. Baker). RESULTS: All 81 patients had primary closure
      after LCBDE between October 2003 and April 2007. The male to female ratio was
      1:3. Median age was 68 years (range 19-90 years). Nineteen (23%) patients had
      obstructive jaundice, 4 (5%) had cholangitis, 7 (8.6%) had acute pancreatitis, 9
      (11.1%) had failed ERCP, and 42 (51.8%) had biliary colic or cholecystitis with
      positive intraoperative cholangiogram (IOC). Those patients were divided into two
      groups: elective LCBDE (ElLCBDE) (n=33, 41%) and emergency LCBDE (EmLCBDE) (n=48,
      59%). There was no significant difference in the median operative time, median
      hospital stay and complication rate. Total laparoscopic clearance rate in this
      series was 95%. CONCLUSIONS: To our knowledge, this is the first publication in
      the literature in which primary closure after laparoscopic common bile duct
      exploration in emergency setting was used. With no significant difference in
      operative time, hospital stay and complications, in experienced hands primary
      closure of CBD in emergency settings is safe and feasible.

PMID- 18622565
TI  - The surgical management of obesity in young women: consideration of the mother's
      and baby's health before, during, and after pregnancy.
AB  - BACKGROUND: Maternal obesity has a substantial associated morbidity and mortality
      affecting both mother and child. This has a major impact on provision of care due
      to increased requirements for both medical and surgical management of the
      consequences that follow obesity in pregnancy. METHODS: A review examined the
      English language literature on Medline databases describing the effect of obesity
      on pregnancy and outcomes of pregnancy after bariatric surgery. Guidelines from
      the National Institute for Clinical Excellence yielded information on selection
      criteria for fertility treatment and bariatric surgery. The World Health
      Organization definitions of overweight and obesity were adhered to throughout
      this review. RESULTS: The level of clinical and morbid obesity has shown a
      dramatic increase in women of childbearing age, with far-reaching consequences
      for both their own health and that of their offspring. Obese women require a
      substantial amount of additional clinical care beyond that offered to women of
      normal weight due to the wide range of medical and obstetric complications they
      experience. Recent evidence suggests that obesity may be implicated in
      approximately one-third of maternal deaths. The consensus of the literature is
      that the best way to reduce obesity-associated morbidity is by weight reduction
      before pregnancy. Where behavioral and medical interventions fail, the most
      successful method is bariatric surgery. The effect of surgery on the outcome of
      subsequent pregnancies indicate improved chances of normal pregnancy, delivery,
      and healthy babies. CONCLUSIONS: Bariatric surgery is a safe and effective method
      of weight loss for morbidly obese women of childbearing age, with favorable
      outcomes for pregnancies after surgery.

PMID- 18622566
TI  - Do hybrid simulator-generated metrics correlate with content-valid outcome
      measures?
AB  - BACKGROUND: Hybrid simulators provide objective metrics for laparoscopic task
      performance. This study aimed to evaluate the correlation between hybrid
      simulator-generated metrics and content-valid outcome measures. METHODS:
      Residents underwent training with a previously validated 5-task simulation model
      (5-TSM). The resident tasks included vessel clipping and dividing, lesion
      excision, loop appendectomy, mesh placement with tacks, and suture perforation
      with intracorporeal knot tying. After training, the residents were tested using
      the open module of a hybrid simulator (ProMIS) with previously validated passing
      scores. Content validity was defined as the extent to which outcome measures
      departed from clinical reality. Content-valid outcome measures (accuracy error,
      knot slippage, leak, operating time, tissue damage) were evaluated by two blinded
      raters. The hybrid simulator-generated metrics were path length and smoothness of
      movements. Values are given as means (standard deviation is not shown). RESULTS:
      Over 23 months, 20 residents underwent training with 5-TSM. Respectively, for
      tasks 1 to 5, the path length was 3,895, 3,472, 4,620, 2,408, and 9,089 mm; the
      smoothness (jerk) was 346, 455, 549, 264, and 910 cm/sec3; the accuracy error was
      0.45, 2.20, 0.55, 0.87, and 0.20 mm; and the knot slippage was 5%. There were no
      leaks. The operating time, respectively, was 54, 61, 135, 43, and 130 s, and the
      tissue damage was 0, 0.28, 0, 0.8, and 0 mm. The interrater reliability was more
      than 0.80 for all the outcome measures except accuracy error (k=0.52). There was
      correlation between path length and operating time (Spearman rho, 0.537-0.709;
      p<0.05) for all the tasks. There was no correlation between path length and
      accuracy error, knot slippage, leak, and tissue damage. No correlation was found
      between smoothness and any of the outcome measures for any of the tasks except
      operating time (Spearman rho, 0.762-0.958; p<0.05). CONCLUSIONS: Although an
      expected strong correlation was observed between hybrid simulator-generated
      metrics and operating time, this study showed no correlation between simulator
      generated metrics and other content-valid outcome measures.

PMID- 18622567
TI  - A quantitative study of disruption in the operating room during laparoscopic
      antireflux surgery.
AB  - BACKGROUND: Many activities performed by team members in the operating room (OR)
      are not directly related to the achievement of the surgical goal. METHODS: A
      video-aided observational field study was conducted in the OR to examine
      disruptive events during laparoscopic antireflux surgery. Disruptive events were
      categorized into one of six groups: instrument change, surgeon position change,
      nurse duty shift, conversation, phone/pager answering, and extraneous
      interruption. The frequency and duration of each type of disruptive event were
      recorded. Events were further categorized based on whether or not they delayed
      the workflow. RESULTS: The average procedure time of 12 observed cases was 123
      min. On average, a total of 114 disruptive events were recorded per hour.
      Intraoperative conversations were recorded with the highest frequency (71
      episodes/h) and longest duration (16 min/h); however, most conversations did not
      delay surgical workflow. The events that generated most surgical delays were
      instrument change (3.4 min/h), which included times for placing essential
      instruments into the surgical site and time spent waiting for an unavailable
      instrument. On average, disruptive events performed in the OR caused 4.1 min of
      delay for each case per hour, corresponding to 6.5% of the procedure time.
      CONCLUSIONS: This study demonstrated the feasibility of using video-aided
      observational studies for developing objective assessment of team quality in the
      OR. Categorizing disruptive events and examining their negative impact on the OR
      time will help to develop methods to eliminate inefficiency inside the OR.

PMID- 18622568
TI  - Needlescopic hysterectomy: incorporation of 3-mm instruments in total
      laparoscopic hysterectomy.
AB  - BACKGROUND: Progression to needlescopic techniques for advanced gynecologic
      procedures currently performed with conventional laparoscopy still is in its
      infancy, and published series are currently lacking in the gynecologic
      literature. This study aimed to report initial experience with incorporating
      needlescopic instruments in the performance of total laparoscopic hysterectomy
      (TLH). METHODS: The study group consisted of 32 consecutive women undergoing
      needlescopic hysterectomy. The control group included 54 women who underwent
      conventional TLH over the preceding 12-month period and met the same inclusion
      criteria as the study group. Conventional TLH was performed using 5-mm working
      ports and a 10-mm laparoscope. The needlescopic hysterectomy differed from the
      conventional laparoscopic procedure in that 3-mm working ports were used as well
      as a 3- or 5-mm laparoscope at the umbilicus. Otherwise, the trocar layout and
      surgical technique were identical. Parameters of technical feasibility (operating
      time, estimated blood loss, perioperative complications) were considered major
      statistical end points. RESULTS: In the study group, all but one procedure were
      performed successfully using the needlescopic approach. One patient in the
      needlescopic group required conversion to standard TLH because of uncontrollable
      bleeding from the uterine artery. The operative time and estimated blood loss of
      needlescopic hysterectomy were comparable with those of standard TLH. No
      significant complication occurred in either group. CONCLUSIONS: For properly
      selected patients, the needlescopic technique can be applied to TLH safely and
      effectively.

PMID- 18622570
TI  - Sequence and phylogenetic analysis of a Chinese very virulent infectious bursal
      disease virus.
AB  - The complete genome sequence of a Chinese very virulent infectious bursal disease
      virus (vvIBDV) strain, Harbin-1, was determined. Based on the sequence analysis,
      the molecular characteristics and potential virulence determinants and origin of
      vvIBDV strains were identified. Phylogenetic analysis indicated that a
      reassortment and/or recombination event may have occurred in the emergence of
      Chinese vvIBDV strains.

PMID- 18622569
TI  - Analysis of genes isolated from plated hemocytes of the Pacific oyster,
      Crassostreas gigas.
AB  - A complementary deoxyribonucleic acid library was constructed from hemocytes of
      Crassostrea gigas that had been plated on poly-lysine plates for 24 h. From this
      library, 2,198 expressed sequence tags (ESTs) of greater than or equal to 100 bp
      were generated and analyzed. A large number of genes that potentially could be
      involved in the physiology of the oyster hemocyte were uncovered. They included
      proteins involved in cytoskeleton rearrangement, proteases and antiproteases,
      regulators of transcription and translation, cell death regulators, receptors and
      their associated protein factors, lectins, signal transduction proteins, and
      enzymes involved in eicosanoid and steroid synthesis and xenobiotic metabolism.
      Based on their relationship with innate immunity, the expression of selected
      genes was analyzed by quantitative polymerase chain reaction in gills from
      bacterial-challenged oysters. Several genes observed in the library were
      significantly upregulated by bacterial challenge including interleukin 17,
      astacin, cystatin B, the EP4 receptor for prostaglandin E, the ectodysplasin
      receptor, c-jun, and the p100 subunit of nuclear factor-kB. Using a similar
      approach, we have been analyzing the genes expressed in trout macrophages. While
      there are significant differences between the types of genes present in
      vertebrate macrophages compared with oyster hemocytes, there are some striking
      similarities including proteins involved in cytoskeletal rearrangement, proteases
      and antiproteases, and genes involved in certain signal transduction pathways
      underlying immune processes such as phagocytosis. Finally, C. virginica homologs
      of some of the C. gigas genes uncovered in the ESTs were obtained by aligning the
      ESTs reported here, against the assembled C. virginica ESTs at the National
      Center for Biotechnology Information.

PMID- 18622571
TI  - Irreversible inhibition of the thermophilic esterase EST2 from Alicyclobacillus
      acidocaldarius.
AB  - Kinetic studies of irreversible inhibition in recent years have received growing
      attention owing to their relevance to problems of basic scientific interest as
      well as to their practical importance. Our studies have been devoted to the
      characterization of the effects that well-known acetylcholinesterase irreversible
      inhibitors exert on a carboxylesterase (EST2) from the thermophilic eubacterium
      Alicyclobacillus acidocaldarius. In particular, sulfonyl inhibitors and the
      organophosphorous insecticide diethyl-p-nitrophenyl phosphate (paraoxon) have
      been studied. The incubation of EST2 with sulfonyl inhibitors resulted in a time
      dependent inactivation according to a pseudo-first-order kinetics. On the other
      hand, the EST2 inactivation process elicited by paraoxon, being the inhibition
      reaction completed immediately after the inhibitor addition, cannot be described
      as a pseudo-first-order kinetics but is better considered as a high affinity
      inhibition. The values of apparent rate constants for paraoxon inactivation were
      determined by monitoring the enzyme/substrate reaction in the presence of the
      inhibitor, and were compared with those of the sulfonyl inhibitors. The
      protective effect afforded by a competitive inhibitor on the EST2 irreversible
      inhibition, and the reactivation of a complex enzyme/irreversible-inhibitor by
      hydroxylamine and 2-PAM, were also investigated. The data have been discussed in
      the light of the recently described dual substrate binding mode of EST2,
      considering that the irreversible inhibitors employed were able to discriminate
      between the two different binding sites.

PMID- 18622572
TI  - A bacterial ice-binding protein from the Vostok ice core.
AB  - Bacterial and yeast isolates recovered from a deep Antarctic ice core were
      screened for proteins with ice-binding activity, an indicator of adaptation to
      icy environments. A bacterial strain recovered from glacial ice at a depth of
      3,519 m, just above the accreted ice from Subglacial Lake Vostok, was found to
      produce a 54 kDa ice-binding protein (GenBank EU694412) that is similar to ice
      binding proteins previously found in sea ice diatoms, a snow mold, and a sea ice
      bacterium. The protein has the ability to inhibit the recrystallization of ice, a
      phenotype that has clear advantages for survival in ice.

PMID- 18622573
TI  - Intratumoral estrogen production in breast carcinoma: significance of aromatase.
AB  - It is well known that estrogens are closely involved in the growth of human
      breast carcinoma, and that the great majority of breast carcinomas express
      estrogen receptor. Recent studies have demonstrated that estrogens are locally
      produced in breast carcinoma by several enzymes. Among these, aromatase is
      generally considered the most important enzyme, and aromatase inhibitors are
      currently used in the treatment of breast carcinoma in postmenopausal women as an
      estrogen deprivation therapy. Therefore, in this review, we summarize the results
      of recent studies on aromatase in breast carcinoma, and we discuss its biological
      and/or clinical significance. Aromatase was expressed in various cell types in
      breast carcinoma, such as carcinoma cells, intratumoral stromal cells and
      adipocytes adjacent to the carcinoma, and the aromatase expression was regulated
      by various factors, including carcinoma cell-stromal cell interactions, cytokines
      and nuclear receptors, depending on the cell types. Aromatase was involved not
      only in local estrogen production but also the inhibition of intratumoral
      androgen synthesis in breast carcinoma. Finally, tissue concentrations of sex
      steroids were significantly higher in noninvasive breast carcinoma, regarded as a
      precursor lesion to invasive carcinoma, than in non-neoplastic breast tissue, and
      various sex steroid-producing enzymes (including aromatase) were abundantly
      expressed in noninvasive breast carcinoma tissue. Therefore, sex steroids are
      locally produced in noninvasive breast carcinoma as well as invasive carcinoma,
      and endocrine therapies may be clinically effective in a select group of
      noninvasive breast carcinoma patients.

PMID- 18622574
TI  - Rheumatologists' knowledge, attitude and current management of fatigue in
      patients with rheumatoid arthritis (RA).
AB  - To describe rheumatologists' knowledge, attitude and current management of
      fatigue in patients with rheumatoid arthritis (RA), a postal questionnaire was
      sent to all rheumatologists (N = 204) and trainees (N = 49), members of the Dutch
      Society of Rheumatology. The overall response rate was 44% (N = 110). In general,
      rheumatologists' knowledge about RA-related fatigue was in accordance with the
      literature but they perceive a lack of their own knowledge about aetiology and
      evidence-based interventions to prevent and treat fatigue. The majority of the
      rheumatologists believe that fatigue is a multi-disciplinary diagnosis and is
      preferably managed by the nurse specialist (34%). Assuming that the patient will
      raise the issue, most of the rheumatologists pay attention to fatigue during the
      first consultation and less often during follow-up consultations. There is a need
      for knowledge about causes and treatments for RA-related fatigue to ensure that
      patient outcomes are improved.

PMID- 18622575
TI  - A cross-sectional study of the relationship between body mass index and clinical
      characteristics, tenderness measures, quality of life, and physical functioning
      in fibromyalgia patients.
AB  - We examined the relationship between body mass index (BMI) and measures of
      tenderness, quality of life, and physical functioning in female fibromyalgia
      (FMS) patients. A random sample of 100 female FMS patients from a database of 550
      FMS individuals was interviewed and assessed according to a structured
      questionnaire that included FMS-related symptoms, measures of tenderness (point
      count and dolorimetry), quality of life (SF-36), physical functioning, and BMI.
      Weight was defined as normal, overweight, and obesity according to BMI. Twenty
      seven percent of the FMS patients had normal BMI, 28% were overweight, and 45%
      were obese. BMI was negatively correlated with quality of life (r = -0.205, P =
      0.044) and tenderness threshold (r = -0.238, P = 0.021) and positively correlated
      with physical dysfunctioning (r = 0.202, P = 0.047) and point count (r = 0.261, P
      = 0.011). Obese FMS patients display higher pain sensitivity and lower levels of
      quality of life. In designing studies that explore factors affecting tenderness,
      BMI should be included in addition to sex, age, etc.

PMID- 18622576
TI  - Use of nonsteroidal anti-inflammatory drugs and coxibs in the elderly. Are we
      following the guidelines?

PMID- 18622577
TI  - Erythropoietins from teleosts.
AB  - The epo genes of many teleosts, including zebrafish, have been cloned following
      the first identification of nonmammalian EPO from fugu in 2004. The zebrafish
      (Danio rerio) animal model is well suited for both developmental and genetic
      analyses for studying vertebrate erythropoiesis. The purpose of this review is to
      provide an update of recent progress in research on teleost EPO with a focus on
      its structure, expression and secretion. The EPO receptor and the downstream
      JAK/STAT signaling pathway are also discussed.

PMID- 18622578
TI  - Control of sperm motility and fertility: diverse factors and common mechanisms.
AB  - Spermatozoa generated in the testis are immature and incompetent for
      fertilization. During their journey toward the egg, the sperm acquire fertility
      and achieving fertilization. These sperm modifications to ensure fertilization
      are induced by many female or male extra-sperm factors: for example, sperm
      motility-activating factors from the egg jelly, sperm attractants from the eggs,
      and decapacitation factors from the seminal plasma. The factors controlling sperm
      fertility are myriad and species specific; they may be peptides, sugar chains, or
      small organic compounds. Nevertheless, the fundamental mechanisms underlying
      fertilization must be common among all animals; increase in [Ca(2+)](i) triggers
      all the steps in the process of fertilization, and cAMP plays important roles in
      many steps. Elucidating the dynamic functional and morphological changes in sperm
      cells is important for understanding the regulation of fertilization. Here, we
      introduce the diversity and generality of the control of sperm fertility.

PMID- 18622579
TI  - Comment to poem by Heather Christine Sinkinson.

PMID- 18622580
TI  - Neural differentiation arrest in embryonal carcinoma cells with forced expression
      of EWS-FLI1.
AB  - Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) has a characteristic
      chimeric oncogene EWS-FLI1, which results from chromosomal translocation t (11;
      22), that is believed to initiate tumorigenesis of EWS/PNET. However, the
      specific details of EWS/PNET oncogenesis and exact role of EWS-FLI1 remain
      largely unknown. In this study we explored the role of EWS-FLI1 in tumor
      differentiation using an embryonal carcinoma cell line P19 as a model, with
      forced expression of EWS-FLI1 in these cells. EWS-FLI1 has been reported to
      promote neural differentiation in fibroblasts, mesenchymal stem cells and
      rhabdomyosarcoma cells. We show forced expression of EWS-FLI1 causes absence of
      retinoic acid-induced neural morphology, and decreases expression of neural
      specific proteins MAPT and NCAM. Critical transcriptional factors for neural
      differentiation and stem cells are also altered in the presence of EWS-FLI1,
      including decreases in levels of Oct-3 and Pax-6, and an increase in the level of
      Id2, which is a target of EWS-FLI1. Increased proliferation and decreased
      apoptotic rates are also observed in P19 cells with forced expression of EWS
      FLI1. Our results raise the possibility that arrest of neural differentiation by
      forced expression of EWS-FLI1 as observed in this study may result from
      dysregulation of the cell cycle and cell proliferation. Taken together, our
      results demonstrate that the modulation of neural differentiation in P19 cells
      which have a stem cell-like pluripotency in vitro can provide a novel model
      system to study the neural differentiation effects of EWS-FLI1 tumorigenesis of
      EWS/PNET.

PMID- 18622581
TI  - Malignant prolactinoma with craniospinal metastasis in a 12-year-old boy.
AB  - The authors report the clinical features of and imaging studies on a rare case of
      pediatric malignant prolactinoma. A 12-year-old boy presented with ataxia,
      blurred vision, and consciousness disturbance. He had received transcranial
      surgery and adjuvant radiotherapy. However, the tumor regrew with craniospinal
      metastasis 16 months after the operation. The relevant literature was reviewed
      regarding the clinical presentation, pathogenesis, treatment approaches, and
      prognosis of malignant prolactinoma.

PMID- 18622583
TI  - Non-invasive automated measurement of cardiac output during stable cardiac
      surgery using a fully integrated differential CO(2) Fick method.
AB  - OBJECTIVES: To re-evaluate the accuracy and precision of a non-invasive method
      for measurement of cardiac output based on the differential CO(2) Fick approach
      using an automated change in respiratory rate delivered by a ventilator under
      control by a prototype measurement system. METHODS: Twenty-four patients during
      coronary artery bypass surgery, pre- and postcardiopulmonary bypass were
      recruited. After routine cannulation including pulmonary artery catheter,
      relaxant general anesthesia was induced. After hemodynamic and ventilatory
      stability were achieved, simultaneous paired measurements were made by the
      differential Fick method and by bolus thermodilution. Measurements were generated
      by inducing a change in respiratory rate by the ventilator under computer
      control. In Group 1, this involved an increase in respiratory rate from 8 to 12
      breaths/min. In Group 2, this involved a decrease from 12 to 6 breaths/min.
      RESULTS: Nineteen measurements were made in each Group, 12 pre-CPB and 7 post
      CPB. In Group 1 mean bias was -0.06 l/min, with a precision of agreement of 0.87
      l/min, r = 0.91. In Group 2 (excluding one outlier) mean bias was -0.07 l/min,
      with a precision of 1.12 l/min, r = 0.71. CONCLUSIONS: Acceptable agreement with
      thermo- dilution during surgery was found, particularly where the ventilatory
      change involved an increase in respiratory rate from a lower baseline. This
      approach has potential to be readily integrated into modern anesthesia delivery
      platforms, allowing routine non-invasive cardiac output measurement.

PMID- 18622582
TI  - High levels of high sensitivity C-reactive protein predict the progression of
      chronic rheumatic mitral stenosis.
AB  - BACKGROUND: High sensitive C-Reactive Protein (hs-CRP) predicts morbidity and
      mortality in various clinical conditions. The effect of hsCRP on progression of
      chronic rheumatic mitral stenosis (CRMS) has not been demonstrated. METHODS AND
      RESULTS: A total of 132 patients with CRMS (95 female, 37 male) and 145 control
      (100 female, 45 male) were included in the study. Baseline clinical,
      echocardiographic, hematologic and hs-CRP measurements were collected
      prospectively. Mean mitral valve area (MVA) was 1.4 +/- 0.3 cm(2), mean wilkins
      valve score value was 8.9 +/- 1.7, left atrial diameter was 5.0 +/- 0.7 cm, left
      atrial area was 37.2 +/- 12.6 cm(2), and systolic pulmonary arterial pressure
      (SPAP) was 44 +/- 11 mmHg in patients with CRMS. The mean levels of hs-CRP value,
      fibrinogen, and mean platelet volume (MPV) were significantly higher in CRMS
      group compared to control group. The levels of hsCRP were found to be positively
      correlated with mean Wilkins valve score value, SPAP, presence of atrial
      fibrillation (AF), left atrial diameter, left atrial area, presence of LASEC(+),
      fibrinogen, and MPV and inversely correlated with MVA in patients with CRMS.
      Linear regression analysis revealed that the hsCRP level independently affects
      mean Wilkins valve score value, left atrial area (LAA), LASEC(+) and AF in the
      patients with CRMS. CONCLUSIONS: These results suggest that increased hsCRP
      levels are associated with CRMS severity. These association may be important when
      treating patients with CRMS.

PMID- 18622585
TI  - Expression of PACAP-like compounds during the caudal regeneration of the
      earthworm Eisenia fetida.
AB  - The regeneration of the ventral nerve cord ganglion and peripheral tissues was
      investigated by radioimmunoassay and immunohistochemistry in the model animal,
      Eisenia fetida (Annelida, Oligochaeta). It is now well-established that pituitary
      adenylate cyclase-activating polypeptide (PACAP) is a neurotrophic factor,
      playing important roles in the development of the nervous system in vertebrate
      animals. Based on the apparent evolutionary conservation of PACAP and on the
      several common mechanisms of vertebrate and invertebrate nervous regeneration,
      the question was raised whether PACAP has any role in the regeneration of the
      earthworm nervous system. As a first step, we studied the distribution,
      concentration, and time-course of PACAP-like immunoreactivity during caudal
      regeneration of both lost segments and the ventral nerve cord ganglia in E.
      fetida. A strong upregulation of PACAP-like immunoreactivity was observed in most
      tissues following injury as determined by radioimmunoassay and
      immunohistochemistry. Significant increases in the concentration of PACAP-like
      compounds were found in the body wall, alimentary canal, and in coelomocytes. The
      most characteristic morphological feature was the accumulation of immunolabeled
      neoblasts in the injured tissues, especially in the ventral nerve cord ganglion
      that initiates and mediates regeneration processes. Our present results show that
      PACAP/PACAP-like peptides accumulate in the regenerating tissues of the
      earthworm, suggesting trophic functions of these compounds in earthworm tissues
      similarly to vertebrate species.

PMID- 18622584
TI  - The sticky business of histone H2AX in V(D)J recombination, maintenance of
      genomic stability, and suppression of lymphoma.
AB  - DNA double strand breaks (DSBs) induced during cellular metabolism, DNA
      replication, and genomic rearrangement events lead to phosphorylation of the H2AX
      core histone variant in surrounding chromatin. H2AX is essential for normal DSB
      repair, maintenance of genomic stability, and suppression of lymphomas with
      clonal translocations and intra-chromosomal deletions. One current focus of our
      lab is to elucidate mechanisms through which H2AX functions in the cellular DNA
      damage response using V(D)J recombination as a model system. A number of
      potential H2AX functions can be readily tested using novel experimental
      approaches developed in our lab. These putative functions include: (1) modulation
      of chromatin accessibility to facilitate kinetics of DSB repair, (2)
      stabilization of broken DNA strands to maintain ends in close proximity, and (3)
      amplification of DNA damage signals. Here, we summarize our recent efforts in
      elucidating mechanisms by which H2AX functions during V(D)J recombination to
      coordinate DSB repair with cellular proliferation and survival to prevent
      translocations and suppress lymphomagenesis.

PMID- 18622586
TI  - Amplitude histogram-based method of analysis of patch clamp recordings that
      involve extreme changes in channel activity levels.
AB  - Many ion channels show low basal activity, which is increased hundreds-fold by
      the relevant gating factor. A classical example is the activation G-protein
      activated K(+) channels (GIRK) by Gbetagamma subunit dimer. The extent of
      activation (relative to basal current), R(a), is an important physiological
      parameter, usually readily estimated from whole cell recordings. However,
      calculation of R(a) often becomes non-trivial in multi-channel patches because of
      extreme changes in activity upon activation, from a seemingly single-channel
      pattern to a macroscopic one. In such cases, calculation of the net current
      flowing through the channels in the patch, I, before and after activation may
      require different methods of analysis. To address this problem, we utilized
      neuronal GIRK channels activated by purified Gbetagamma in excised patches of
      Xenopus oocytes. Channels were expressed at varying densities, from a few to
      several hundreds per patch. We present a simple and fast method of calculating I
      using amplitude histogram analysis and establish its accuracy by comparing with I
      calculated from event lists. This method allows the analysis of extreme changes
      in I in multichannel patches, which would be impossible using the standard
      methods of idealization and event list generation.

PMID- 18622587
TI  - [Acute hearing loss from scuba-diving holidays: diagnosis and treatment of
      barotrauma of the inner ear].
AB  - A 35-year-old diver noticed hearing loss and tinnitus after his diving holiday.
      He presented to the Lubeck clinical practice for divers, and we found vascular
      injections on the eardrum. Audiometry showed a high-degree hearing loss of 40-60
      dB. Under the assumption of a perilymphatic fistula, we performed a tympanoscopy
      with covering of the oval and round windows. Bone-conduction hearing improved
      immediately postoperatively to 25 dB. A postoperative rheological infusion
      treatment was given. After 6 months the diver was assessed fit to dive with
      almost normal inner ear function.

PMID- 18622588
TI  - [Computer-aided discectomy and corpectomy in anterior reconstruction of the
      injured thoracolumbar spine. A prospective, controlled clinical trial].
AB  - BACKGROUND: In anterior reconstruction of the unstable thoracolumbar spine,
      discectomy and corpectomy are technically demanding steps requiring maximal
      surgical precision. This study investigated the feasibility of computer-aided
      guidance for discectomy and corpectomy. It also analysed the precision,
      advantages, and disadvantages of the procedure. PATIENTS AND METHODS: Vertebral
      body fractures of the non-osteoporotic thoracolumbar spine addressed by
      discectomy/corpectomy and subsequent implant interposition (cage, tricortical
      strut graft) for anterior reconstruction were included. All surgical steps were
      done under endoscopic assistance. In the trial group, discectomy and corpectomy
      were performed with computer-aided guidance; in the control group, no computer
      navigation was used. The time required for surgery was noted. To assess surgical
      precision, decentralization of the implant in the frontal plane was measured in
      postoperative x-rays and computed tomography. Additionally, parallel alignment of
      vertebral body end plates with the implant was evaluated. RESULTS: The trial
      group (TG) consisted of 16 patients, and the control group (CG) of 10 patients.
      Fractures were localized between T10 and L1 in TG, and between T9 and L1 in CG.
      Operating time was significantly shorter in CG: 104+/-28 min compared with 229+/
      64 min in TG (p<0.0005). In contrast, data on surgical precision showed no
      statistically significant differences between the 2 groups for either
      decentralization or parallel endplate alignment of implants. Remarkably, for CG
      we noted 2 cases of cage subsidence into an adjacent end plate, whereas for TG
      this was noted in only 1 case. However, this difference was not statistically
      significant. CONCLUSION: Computer-aided guidance for anterior reconstruction of
      the thoracolumbar spine is a technically feasible option that may help in
      performing discectomy and corpectomy. However, this technique significantly
      prolongs the operating time. There were no differences in the precision of
      implant positioning between the groups. However, during discectomy the use of
      computer navigation may possibly add to the protection of adjacent end plates.

PMID- 18622589
TI  - [Interventional emergency embolization for severe pelvic ring fractures with
      arterial bleeding. Integration into the early clinical treatment algorithm].
AB  - OBJECTIVE: Presentation of our own experiences and results of an early clinical
      algorithm for treatment integrating emergency embolization (TAE) in cases of
      unstable pelvic ring fractures with arterial bleeding. METHOD: Consecutive
      patient series from April 2002 to December 2006 at a level 1 trauma center. The
      data of the online shock room documentation (Traumawatch) of patients with a
      pelvic fracture and arterial bleeding detected on multislice computed tomography
      (MSCT) were examined for the following parameters: demographic data, injury
      mechanism, fracture classification according to Tile/AO and severity of the
      pelvic injury assessed with the Abbreviated Injury Score (AIS), accompanying
      injuries with elevation of the cumulative injury severity according to the Injury
      Severity Score (ISS), physiological admission parameters (circulatory parameters
      and initial Hb value) as well as transfusion requirement during treatment in the
      shock room, time until embolization, duration of embolization, and source of
      bleeding. RESULTS: Of a total of 162 patients, arterial bleeding was detected in
      21 patients by contrast medium extravasation on MSCT, 12 of whom were men and 9
      women with an average age of 45 (14-80) years. The mechanism of injury was high
      energy trauma in all cases. In 33% it involved type B pelvic fractures and in 67%
      type C fractures with an average AIS pelvis of 4.4 points (3-5) and a total
      severity of injury with the ISS of 37 points (21-66). Upon admission 47.6%
      presented hemodynamic instability with an average Hb value of 7.8 g/dl (3.2-12.4)
      and an average transfusion requirement of 6 red blood cell units (4-13). The time
      until the TAE was started was on average 62 min (25-115) with a duration period
      of the TAE of 25 min (15-67). Branches of the internal iliac artery were
      identified as the sole source of bleeding. The success rate of TAE amounted to
      over 90%. CONCLUSION: Interventional TAE represents an effective as well as a
      fast procedure for hemostasis of arterial bleeding detected on MSCT in patients
      with pelvic fractures. If an experienced radiologist on 24-h stand-by is assured
      and the infrastructure is efficient, this can be performed shortly after hospital
      admission and therefore should be integrated into the early clinical treatment
      protocol.

PMID- 18622590
TI  - [How can tumor drug therapy be implemented in urooncology?].

PMID- 18622591
TI  - [How do I measure outcome in the hospital setting?].

PMID- 18622592
TI  - [System of attending physicians--a critical assessment].

PMID- 18622593
TI  - Long-term exposure of mouse pancreatic islets to oleate or palmitate results in
      reduced glucose-induced somatostatin and oversecretion of glucagon.
AB  - AIMS/HYPOTHESIS: Long-term exposure to NEFAs leads to inhibition of glucose
      induced insulin secretion. We tested whether the release of somatostatin and
      glucagon, the two other major islet hormones, is also affected. METHODS: Mouse
      pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or
      without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin
      during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet
      content of the two hormones were determined. Lipid-induced changes in islet cell
      ultrastructure were assessed by electron microscopy. RESULTS: Culture at 15
      mmol/l glucose increased islet glucagon content by approximately 50% relative to
      that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or
      palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50%
      (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon
      secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l
      glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished
      the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin
      content was unaffected by glucose and lipids, but glucose-induced somatostatin
      secretion was reduced by approximately 50% following long-term exposure to either
      of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l
      glucose. Ultrastructural evidence of lipid deposition was seen in <10% of non
      beta cells but in >80% of the beta cells. CONCLUSIONS/INTERPRETATION: Long-term
      exposure to high glucose and/or NEFA affects the release of somatostatin and
      glucagon. The effects on glucagon secretion are very pronounced and in type 2
      diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.

PMID- 18622594
TI  - The development of microalbuminuria is associated with raised longitudinal
      adiponectin levels in female but not male adolescent patients with type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: We determined the longitudinal relationship between adiponectin
      levels and the development of microalbuminuria in an inception cohort of children
      with type 1 diabetes. METHODS: Blood samples collected annually over a median of
      9.0 (range 1.3-14.9) years were assayed for adiponectin and HbA(1c) in 55
      children (36 girls) with type 1 diabetes and microalbuminuria whose age of onset
      of diabetes was 9.4 years (range 2.2-15.4). Samples were also assayed from
      normoalbuminuric children (controls) matched for age, sex and duration of
      diabetes. RESULTS: Overall, adiponectin levels were higher in girls than in boys,
      but only after 11 years of age (median [range]: 15.3 [5.8-124.4] vs 11.6 [4.1
      26.5] mg/l, p < 0.001). Furthermore, adiponectin levels were higher in girls with
      microalbuminuria than in control girls, but this was only apparent after the
      onset of microalbuminuria (p = 0.001, adjusted for BMI, daily insulin dose,
      HbA(1c) and age). In boys, adiponectin levels did not differ between those with
      microalbuminuria and controls. Further sex-related discordant associations with
      adiponectin levels were observed; in girls, adiponectin levels were positively
      related to HbA(1c) levels (r = 0.2, p = 0.05) and urine albumin excretion (r =
      0.3, p < 0.05) and inversely related to BMI (r = -0.2, p < 0.05). These
      associations were absent in boys. CONCLUSIONS/INTERPRETATION: In adolescent girls
      with type 1 diabetes but not in boys, adiponectin levels increase with increasing
      urine albumin excretion and onset of microalbuminuria. Although causal links
      cannot be inferred, this sexual dimorphism may reflect interactive effects of
      hyperglycaemia and sex steroids on risk of complications and adiponectin
      production.

PMID- 18622595
TI  - [3-Tesla MRI vs. arthroscopy for diagnostics of degenerative knee cartilage
      diseases: preliminary clinical results].
AB  - BACKGROUND: The literature contains only a few studies investigating the magnetic
      resonance imaging (MRI) diagnostics of degenerative cartilage diseases. Studies
      on MRI diagnostics of the cartilage using field strengths of 3-Tesla demonstrate
      promising results. To assess the value of 3-Tesla MRI for decision making
      regarding conservative or operative treatment possibilities, this study focused
      on patients with degenerative cartilage diseases. METHODS: Thirty-two patients
      with chronic knee pain, a minimum age of 40 years, a negative history of trauma,
      and at least grade II degenerative cartilage disease were included. Cartilage
      abnormalities detected at preoperative 3-Tesla MRI (axial/koronar/sagittal PD-TSE
      SPAIR, axial/sagittal 3D-T1-FFE, axial T2-FFE; Intera 3.0T, Philips Medical
      Systems) were classified (grades I-IV) and compared with arthroscopic findings.
      RESULTS: Thirty-six percent (70/192) of the examined cartilage surfaces
      demonstrated no agreement between MRI and arthroscopic grading. In most of these
      cases, grades II and III cartilage lesions were confounded with each other.
      Regarding the positive predictive values, the probability that a positive finding
      in MRI would be exactly confirmed by arthroscopy was 39-72%. In contrast,
      specificities and negative predictive values of different grades of cartilage
      diseases were 85-95%. CONCLUSIONS: Regarding the high specificities and negative
      predictive values, 3-Tesla MRI is a reliable method for excluding even slight
      cartilage degeneration. In summary, in degenerative cartilage diseases, 3-Tesla
      MRI is a supportive, noninvasive method for clinical decision making regarding
      conservative or operative treatment possibilities. However, the value of
      diagnostic arthroscopy for a definitive assessment of the articular surfaces and
      for therapeutic planning currently cannot be replaced by 3-Tesla MRI. This
      applies especially to treatment options in which a differentiation between grade
      II and III cartilage lesions is of interest.

PMID- 18622596
TI  - Risk factors and prognosis of catheter-related bloodstream infection in
      critically ill patients: a multicenter study.
AB  - OBJECTIVE: To assess the risk factors associated with CR-BSI development in
      critically ill patients with non-tunneled, non-cuffed central venous catheters
      (CVC) and the prognosis of the episodes of CR-BSI. Design and setting;
      prospective, observational, multicenter study in nine Spanish Hospitals.
      PATIENTS: All subjects admitted to the participating ICUs from October 2004 to
      June 2005 with a CVC. INTERVENTIONS: None. MEASUREMENT AND RESULTS: Overall,
      1,366 patients were enrolled and 2,101 catheters were analyzed. Sixty-six
      episodes of CR-BSI were diagnosed. The incidence of CR-BSI was significantly
      higher in CVC compared with peripherically inserted central venous catheters
      (PICVC) without significant differences among the three locations of CVC. In the
      multivariate analysis, duration of catheterization and change over a guidewire
      were the independent variables associated with the development of CR-BSI whereas
      the use of a PICVC was a protective factor. Excluding PICVC, 1,598 conventional
      CVC were analyzed. In this subset, duration of catheterization, tracheostomy and
      change over a guidewire were independent risk factors for CR-BSI. A multivariate
      analysis of predictors for mortality among 66 patients with CRSI showed that
      early removal of the catheter was a protective factor and APACHE II score at the
      admission was a strong determinant of in-hospital mortality. CONCLUSIONS:
      Peripherically inserted central venous catheters is associated with a lower
      incidence of CR-BSI in critically ill patients. Exchange over a guidewire of CVC
      and duration of catheterization are strong contributors to CR-BSI. Our results
      reinforce the importance of early catheter removal in critically ill patients
      with CR-BSI.

PMID- 18622597
TI  - Ignicoccus hospitalis and Nanoarchaeum equitans: ultrastructure, cell-cell
      interaction, and 3D reconstruction from serial sections of freeze-substituted
      cells and by electron cryotomography.
AB  - Ultrastructure and intercellular interaction of Ignicoccus hospitalis and
      Nanoarchaeum equitans were investigated using two different electron microscopy
      approaches, by three-dimensional reconstructions from serial sections, and by
      electron cryotomography. Serial sections were assembled into 3D reconstructions,
      for visualizing the unusual complexity of I. hospitalis, its huge periplasmic
      space, the vesiculating cytoplasmic membrane, and the outer membrane. The
      cytoplasm contains fibres which are reminiscent to a cytoskeleton. Cell division
      in I. hospitalis is complex, and different to that in Euryarchaeota or Bacteria.
      An irregular invagination of the cytoplasmic membrane is followed by separation
      of the two cytoplasms. Simultaneous constriction of cytoplasmic plus outer
      membrane is not observed. Cells of N. equitans show a classical mode of cell
      division, by constriction in the mid-plane. Their cytoplasm exhibits two types of
      fibres, elongated and ring-shaped. Electron micrographs of contact sites between
      I. hospitalis and N. equitans exhibit two modes of interaction. One is indirect
      and mediated by thin fibres; in other cells the two cell surfaces are in direct
      contact. The two membranes of I. hospitalis cells are frequently seen in direct
      contact, possibly a prerequisite for transporting metabolites or substrates from
      the cytoplasm of one cell to the other. Rarely, a transport based on cargo
      vesicles is observed between I. hospitalis and N. equitans.

PMID- 18622599
TI  - Separation and identification of trinucleotide-melphalan adducts from
      enzymatically digested DNA using HPLC-ESI-MS.
AB  - Melphalan is a bifunctional alkylating agent that covalently binds to the
      nucleophilic sites present in DNA. In this study we investigated oligonucleotides
      prepared enzymatically from DNA modified with melphalan. Calf thymus DNA was
      incubated in-vitro with melphalan and the resulting modifications were
      enzymatically cleaved by means of benzonase and nuclease S1. Efficient sample
      preconcentration was achieved by solid-phase extraction, in which phenyl phase
      cartridges resulted in better recovery of the modified species than C(18). The
      applied enzymatic digestion time resulted in production of trinucleotide adducts
      which were efficiently separated and detected by use of reversed-phase HPLC
      coupled to an ion-trap mass spectrometer with electrospray ionization. It was
      assumed that melphalan could act as both a monofunctional and bifunctional
      alkylating agent. Mono-alkylated adducts were much more abundant, however, and
      the alkylation site was located on the nucleobases. On the other hand, we
      unequivocally identified cross-link formation in DNA, even though at low
      abundance and only a few adduct types were detected.

PMID- 18622600
TI  - Slower onset of vasodilating action of brain natriuretic peptide (BNP) compared
      to atrial natriuretic peptide (ANP) in human forearm resistant vessels.
AB  - PURPOSE: To investigate possible differences in the time course of vasodilating
      effects of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)
      in humans. METHODS: We measured forearm blood flow (FBF) by strain gauge
      plethymography and cyclic GMP spillover during and after intra-arterial infusions
      of BNP and ANP at 16.2 pmol/min for 30 min in healthy subjects. RESULTS: The
      steady-state responses of FBF and cyclic GMP to the infusion were achieved
      approximately 20 min after commencement of the infusion of BNP, but within 5 min
      for ANP, with similar magnitudes of maximum responses. These parameters more
      slowly returned to the baseline value after withdrawal of the BNP infusion than
      after the ANP infusion. CONCLUSION: The onset and disappearance of the guanylate
      cyclase-stimulating and vasodilating effects of BNP were significantly slower
      than those of ANP. This differing mode of vasodilator action may be relevant to
      the therapeutic use of natriuretic peptides.

PMID- 18622598
TI  - Substrate binding to cytochromes P450.
AB  - P450s have attracted tremendous attention owing to not only their involvement in
      the metabolism of drug molecules and endogenous substrates but also the unusual
      nature of the reaction they catalyze, namely, the oxidation of unactivated C-H
      bonds. The binding of substrates to P450s, which is usually viewed as the first
      step in the catalytic cycle, has been studied extensively via a variety of
      biochemical and biophysical approaches. These studies were directed towards
      answering different questions related to P450s, including mechanism of oxidation,
      substrate properties, unusual substrate oxidation kinetics, function, and active
      site features. Some of the substrate binding studies extending over a period of
      more than 40 years of dedicated work have been summarized in this review and
      categorized by the techniques employed in the binding studies.

PMID- 18622601
TI  - Assessing ventricular size: is subjective evaluation accurate enough? New MRI
      based normative standards for 19-year-olds.
AB  - INTRODUCTION: To create new standards for radiological indices of dilated
      ventricles and to compare these with subjectively assessed ventricular size.
      METHODS: One hundred healthy controls (54 females), birth weight above 3,000 g,
      were followed throughout childhood as part of a longitudinal study of ex
      prematures. All had a 3 Tesla brain magnetic resonance scan at age 17-20, and the
      following measurements were performed: biparietal and occipitofrontal diameters,
      width and depth of the frontal and occipital horns, diameter of the third
      ventricle and the frontal sub-arachnoid space. Ventricular size was judged
      subjectively by two neuroradiologists as being normal, or mildly, moderately or
      severely dilated. RESULTS: Head circumference was 31 mm higher for males than for
      females (95% confidence interval (CI) 25-28, p < 0.001). Similar, ventricular
      size except for the depth of the right frontal horn was larger for male; however,
      the observed differences were partly accounted for by the larger head
      circumference. Normative sex specific standards for different cerebral
      measurements were presented as mean and ranges and additional 2.5, 10, 50, 90,
      97.5 percentiles. The mean depth of the left ventricle was larger than the right
      for males, with an observed difference of 0.6 mm in male (95% CI 0.2-0.9, p =
      0.005). The mean width of the left ventricle was larger than the right for
      females, with an observed difference of 0.4 mm in male (95% CI 0.1-0.7, p =
      0.018). Two subjects were judged to have moderately and 36 to have mildly dilated
      ventricles by observer one, while figures for observer two were one and 14.
      Overall, the two observers agreed on 15 having either mild or moderate dilatation
      (kappa 0.43). For both sexes, the mean depth of the frontal horns as well as of
      the larger occipital horns differed significantly between the no dilatation and
      the mild/moderate dilatation groups. CONCLUSION: In our unselected cohort of
      healthy 19-year-olds, a high total of 14% was diagnosed to have dilated cerebral
      ventricles when subjectively assessed by an experienced neuroradiologist,
      underscoring the need for our new normative standards.

PMID- 18622602
TI  - The relationship of transverse sinus stenosis to bony groove dimensions provides
      an insight into the aetiology of idiopathic intracranial hypertension.
AB  - INTRODUCTION: Transverse sinus tapered narrowings are frequently identified in
      patients with idiopathic intracranial hypertension (IIH); however, it remains
      unclear whether they are primary stenoses or whether they occur secondary to
      raised cerebrospinal fluid pressure. Computed tomographic venography demonstrates
      both the morphology of the venous system and the adjacent bony grooves so it may
      provide an insight into the aetiology of these transverse sinus stenoses.
      MATERIALS AND METHODS: Tapered transverse sinus narrowings (>50%) were studied in
      19 patients without IIH and 14 patients with IIH. Computed tomography vascular
      studies were reviewed and the dimensions of the venous sinuses and bony grooves
      at the sites of maximum and minimum transverse sinus area dimensions were
      recorded. RESULTS: There was demonstrated to be a strong correlation of bony
      groove height with venous sinus height at the largest portions of the transverse
      sinus in both IIH patients and non-IIH subjects as well as at the transverse
      sinus narrowing in non-IIH subjects. There was a discordant relationship between
      bony groove height and venous sinus height at the site of transverse sinus
      stenoses in IIH patients. In 5/23 IIH transverse sinus stenoses, the bony groove
      height was proportionate to that seen in non-IIH subjects. There were a further
      8/23 cases where the small or absent sinus was associated with an absent bony
      groove. CONCLUSION: Transverse sinus tapered narrowings in subjects without IIH
      and in the majority of patients with IIH were associated with proportionately
      small or absent grooves, and these are postulated to be primary or fixed. Some
      patients with IIH demonstrate tapered transverse sinus stenoses with
      disproportionately large bony grooves, suggesting a secondary or acquired
      narrowing. This implies a varied aetiology for the transverse sinus stenoses of
      IIH.

PMID- 18622604
TI  - Structure and function of ion channels.

PMID- 18622603
TI  - Growth outcomes and complications after radiologic gastrostomy in 120 children.
AB  - BACKGROUND: Enteral feeding is ideal for children with low caloric intake. It can
      be provided through different methods, including nasogastric, nasojejunal,
      gastrostomy, or gastrojejunostomy tubes. OBJECTIVE: To assess growth outcomes of
      pediatric patients following retrograde percutaneous gastrostomy (RPG) and
      compare complications with those following other gastrostomy methods. MATERIALS
      AND METHODS: We retrospectively reviewed 120 random RPG patients from 2002 to
      2003 (mean follow-up, 2.7 years). Patient weights and growth percentiles were
      recorded at insertion, and at 0-5 months, 6-12 months, and 18-24 months after
      insertion, and then compared using a Student's t-test. Complications and tube
      maintenance issues (TMIs) were recorded. RESULTS: Gastrostomy tube insertion was
      successful in all 120 patients (59 boys, 61 girls; mean age 4.3 years). The most
      common underlying diagnosis was neurologic disease (29%, 35/120) and the main
      indication was inadequate caloric intake (24%, 29/120). Significant increases in
      growth percentile for the entire population were demonstrated between insertion
      and 0-5 months (18.7-25.3; P<0.001) and between insertion and 18-24 months (18.7
      25.8; P<0.001). In boys and girls significant growth increases occurred between
      insertion and 0-5 months (boys P=0.004; girls P=0.01). There were 11 major
      postprocedural complications, 100 minor complications and 169 TMIs. CONCLUSION:
      RPG provides long-term enteral nutrition in the pediatric population and
      increases growth significantly 6 and 24 months after insertion. Minor
      complications and TMIs are frequent.

PMID- 18622605
TI  - Surgical evaluation of magnetic resonance imaging findings in piriformis muscle
      syndrome.
AB  - OBJECTIVE: The objective of this study was to evaluate the accuracy of magnetic
      resonance imaging (MRI) in the diagnosis of the piriformis muscle syndrome (PMS).
      MATERIALS AND METHODS: In ten patients, seven female and three male, with a long
      history of clinical symptoms of the PMS, an MRI was performed as the last
      preoperative diagnostic tool. All patients were imaged using 2T MR system
      (Elscint, Haifa, Israel). Axial and coronal spin-echo, fast spin-echo (FSE), and
      fat-suppressed FSE-weighted images were made through the pelvic region with 3-mm
      section thickness and a 0.5-mm gap to show the whole piriformis muscle and the
      course of sciatic nerve on its way out of the pelvis. A routine examination also
      included axial fast spin-echo T2, three-dimensional gradient echo. RESULTS: In
      seven cases, an MRI abnormality for the PMS was found. In two women, the MRI
      demonstrated a bigastric appearance of the piriformis muscle with a tendinous
      portion between the muscle heads and the course of the common peroneal nerve
      through the muscle between the tendinous portions of the muscle. In one female
      patient, the common peroneal nerve passed through the hypertrophied piriformis
      muscle. In four patients, the MRI showed a hypertrophied aspect of the piriformis
      muscle and an anteriorly displaced sciatic nerve. All MRI findings were confirmed
      surgically. In three patients, no apparent abnormalities could be observed, but
      after a surgical treatment, i.e., a tenotomy of the piriformis muscle and
      neurolysis of the sciatic nerve, all symptoms disappeared. CONCLUSION: In
      piriformis muscle syndrome, MRI may demonstrate signal abnormalities of the
      sciatic nerve as well as its relationship with the normal and abnormal piriformis
      muscle.

PMID- 18622606
TI  - Relationships between plain-film radiographic patterns and clinicopathologic
      variables in AJCC stage II osteosarcoma.
AB  - OBJECTIVE: In this retrospective study, we assessed the plain-film radiographic
      patterns of American Joint Committee on Cancer (AJCC) stage II osteosarcoma and
      analyzed the relationship between these patterns and clinicopathologic variables.
      MATERIALS AND METHODS: We retrospectively reviewed 347 patients with AJCC stage
      II osteosarcoma who were treated at our institute. Patients were divided into
      three groups based on radiographic patterns, i.e., osteoblastic, osteolytic, and
      mixed. Fisher's exact chi-square test was performed to analyze correlations
      between radiographic patterns and clinicopathological variables. RESULTS: One
      hundred and eighty-eight patients had an osteoblastic tumor, 101 had an
      osteolytic tumor, and 58 had a mixed tumor. Tumors with an osteoblastic pattern
      showed a tendency to have the following characteristics: AJCC stage II-B,
      osteoblastic or chondroblastic subtype, and no pathologic fracture. Conversely,
      osteolytic tumors were frequently of AJCC stage II-A, had a fibroblastic or rare
      subtype, and were associated with a pathologic fracture. Finally, mixed tumors
      were frequently found in men. No survival difference was found according to
      radiographic pattern. CONCLUSIONS: Plain-film radiographic patterns were found to
      be related with clinicopathological features. We believe that it could be used to
      provide valuable information for treatment decision-making in cases of high-grade
      extremity osteosarcoma.

PMID- 18622607
TI  - MR findings in patients with disabling musculocutaneous chronic graft-versus-host
      disease.
AB  - OBJECTIVE: To describe musculocutaneous MR-findings responsible for disability in
      chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell
      transplantation (HCT). MATERIAL AND METHODS: Between June 2005 and February 2008,
      we performed whole-body musculoskeletal magnetic resonance imaging (MRI; n = 12)
      or regional MRI (n = 4) in 16 consecutive patients presenting with disabling
      sclerodermatous cGVHD (e.g., skin edema, fixed deep dermal sclerosis, joint
      contractures, painful muscular contractures, or myalgia). RESULTS: In all
      patients, MRI showed musculocutaneous abnormalities reflecting different degrees
      of inflammation and collagen tissue involvement of the skin (n = 10),
      subcutaneous fat tissue (n = 13), muscle fasciae (n = 16), subfascial muscular
      septae (n = 6), or findings compatible with myositis (n = 3). The most frequently
      involved muscle fasciae comprised those of the vastus lateralis muscle (n = 12),
      biceps femoris muscle (n = 11), gastrocnemius medialis muscle (n = 8), serratus
      anterior muscle, and latissimus dorsi muscle (each, n = 5). Increased signal of
      involved tissues on STIR-images and fat-saturated postgadolinium T1-weighted
      images represented the most frequent MR-signal abnormalities. CONCLUSION: MR
      imaging of musculocutaneous cGVHD allows accurate evaluation including assessment
      of deep tissue infiltration and assists in the differential diagnosis.

PMID- 18622608
TI  - Magnetic resonance imaging of double-bundle anterior cruciate ligament
      reconstruction.
AB  - Reconstruction of the anterior cruciate ligament (ACL) using the double-bundle
      technique is getting highly increasing attention. This surgical approach uses two
      separate tendon grafts with the intention to reconstruct both anatomic bundles in
      order to restore the full biomechanical function of the original ligament. With
      the increasing popularity of this technique, radiologists will be more frequently
      confronted with patients who underwent this surgical procedure. The aims of this
      essay are to briefly describe the basic biomechanical and surgical principles and
      to summarize the magnetic resonance imaging findings of the knee after double
      bundle ACL reconstruction.

PMID- 18622609
TI  - Atypically thick and high location of the Wrisberg ligament in patients with a
      complete lateral discoid meniscus.
AB  - The purpose of this study was to document the relationship between a discoid
      lateral meniscus and a thickened Wrisberg ligament with a higher location on the
      medial femoral condyle.Between July 2002 and February 2006, 100 consecutive
      patients who had a complete lateral discoid meniscus and another 100 patients
      without a discoid lateral meniscus (control group) were included. Two
      radiologists retrospectively reviewed all of the magnetic resonance images,
      paying particular attention to the presence and thickness of the Wrisberg
      ligament and the location of the attachment of the Wrisberg ligament to the
      medial femoral condyle (types I, II, or III). We assumed that type I Wrisberg
      ligaments had a higher location.All 141 patients had a Wrisberg ligament (71%).
      There were 73 patients (73%) in the discoid group and 68 patients (68%) in the
      non-discoid group. The mean thickness of the Wrisberg ligament in the patients in
      the discoid and non-discoid groups was 2.1 mm (range, 0.4-4.7 mm; median, 2.1 mm)
      and 1.6 mm (range, 0.4-4.5 mm; median, 1.3 mm), respectively. The Wrisberg
      ligaments of the discoid group were thicker than the non-discoid group (p =
      0.0002). The Wrisberg ligament was attached to the upper part of the medial
      femoral condyle in the discoid group more often than in the non-discoid group (p
      < 0.0001).

PMID- 18622610
TI  - Imaging of painful scoliosis.
AB  - Scoliosis is defined as a lateral deviation of the spine from the normal plumb
      line. Commonly, there is a rotational component and deviation also in the
      sagittal plane (kyphosis or hyperlordosis). When scoliosis presents in adults, it
      is often painful. In contrast, back pain in a child is considered rare, and
      serious underlying pathology should be excluded, particularly since idiopathic
      scoliosis is typically painless. A painful scoliosis in a child or adolescent,
      especially if the patient has a left-sided curve, should be examined thoroughly.
      The aim of this review is to illustrate the causes of a painful scoliosis in
      children, adolescents and adults.

PMID- 18622611
TI  - Cardiac sympathetic nerve abnormality predicts ventricular tachyarrhythmic events
      in patients without conventional risk of sudden death.
AB  - PURPOSE: Patients with structural heart disease, severe left ventricular
      dysfunction, or history of cardiac arrest are at increased risk of sudden cardiac
      death. However, a useful marker for predicting sudden cardiac death is not
      clarified in low-risk patients without those conventional risks. We hypothesized
      that cardiac sympathetic nerve system (SNS) abnormality would be associated with
      ventricular tachyarrhythmic events in low-risk patients with ventricular
      tachycardia (VT). METHODS: Iodine-123 metaiodobenzylguanidine ((123)I-MIBG)
      scintigraphy was performed in 50 patients (mean+/-standard deviation, age 54 +/-
      16 years, 52% males) with VT who did not have structural heart disease, severe
      left ventricular dysfunction, or history of cardiac arrest, and SNS activity was
      assessed from heart/mediastinal (H/M) ratio on delayed images. RESULTS: Over 11
      years of follow-up, three patients had sudden deaths (6%) and nine patients had
      sustained ventricular tachyarrhythmic events (18%). SNS abnormality, defined as
      H/M ratio <2.8, was predictive of sudden death or ventricular tachyarrhythmic
      events (45% in nine of 20 patients with SNS abnormality vs 16.7% in three of 30
      patients without SNS abnormality, p = 0.005). After adjustment for potential
      confounding variables including slight left ventricular dysfunction, SNS
      abnormality remained independently predictive of ventricular tachyarrhythmic
      events with a hazard ratio of 5.3 (95% confidence interval = 1.4 to 20.8, p =
      0.016). CONCLUSION: SNS abnormality is a readily available and powerful predictor
      of recurrent ventricular tachyarrhythmic events in patients with VT who did not
      have conventional risk of sudden cardiac death. (123)I-MIBG scintigraphy can
      provide prognostic information of VT patients without conventional risk.

PMID- 18622612
TI  - Dynamic 18F-fluoride small animal PET to noninvasively assess renal function in
      rats.
AB  - PURPOSE: Renal function can be quantified by both laboratory and scintigraphic
      methods. In the case of small animal diagnostics, scintigraphic image-based
      methods are ideal since they can assess split renal function, work noninvasively,
      and can be repeated. The aim of this study is to validate a (18)F-PET-based
      method to quantify renal function in rats. MATERIALS AND METHODS: Fluoride
      clearance was calculated from a dynamic whole body listmode acquisition of 60 min
      length in a small animal PET scanner following an i.v. injection of 15 MBq (18)F
      fluoride. Volumes of interest (VOIs) were placed in the left ventricle and the
      bladder as well as traced around the kidney contours. The respective time
      activity curves (TAC) were calculated. The renal (18)F-clearance was calculated
      by the ratio of the total renal excreted activity (bladder VOI) and the integral
      of the blood TAC. PET-derived renal function was validated by intraindividual
      measurements of creatinine clearance (n = 23), urea clearance (n = 23), and
      tubular excretion rate (TER-MAG3). The split renal function was derived from the
      injection of the clinically available radionuclide (99m)Tc-mercaptotriglycine by
      blood sampling and planar renography (n = 8). RESULTS: In all animals studied,
      PET revealed high-quality TACs. PET-derived renal fluoride clearance was linearly
      correlated with intraindividual laboratory measures (PET vs. creatinine: r =
      0.78; PET vs. urea: r = 0.73; PET vs. TER-MAG3: r = 0.73). Split function was
      comparable ((18)F-PET vs. MAG3-renography: r = 0.98). PET-derived measures were
      highly reproducible. CONCLUSIONS: (18)F-PET is able to noninvasively assess renal
      function in rats and provides a significant potential for serial studies in
      different experimental scenarios.

PMID- 18622613
TI  - The effect of education on rCBF changes in Alzheimer's disease: a longitudinal
      SPECT study.
AB  - PURPOSE: To determine the relationship of differing levels of education on
      regional cerebral blood flow (rCBF) in patients with Alzheimer's disease (AD).
      METHODS: Fifty-three patients with AD followed-up for an average of 36 months
      were divided into the high-educated group (HE, >or=12 years of schooling) and low
      educated group (LE, <12 years of schooling). The cognitive and functional
      impairment was assessed using the Mini-Mental State Examination (MMSE) and the
      Functional Assessment Staging (FAST), respectively. Initial and follow-up rCBF
      were assessed using SPECT with N-isopropyl-p-[(123)I]-iodoamphetamine and the
      SPECT data were analyzed by 3D-stereotactic surface projections. RESULTS: At
      initial evaluation, the HE group had greater rCBF deficits in the parietotemporal
      regions than did the LE group, even though both groups had comparable MMSE and
      FAST scores. When compared with initial SPECT, follow-up SPECT showed a
      significant rCBF reduction in widespread regions, including the frontal,
      parietal, temporal, and limbic lobes of the HE group, while it a significant rCBF
      reduction in scattered and small regions of the parietotemporal, cingulate, and
      occipital areas of the LE group, as the HE group had faster cognitive and
      functional decline than the LE group. CONCLUSION: The HE group showed lower rCBF
      at initial SPECT than the LE group, suggesting more advanced AD pathology. As a
      result, the HE group demonstrated a more extensive and severe reduction of rCBF
      on follow-up SPECT in association with faster cognitive and functional decline
      than the LE group. Our SPECT study provides stronger support for the cognitive
      reserve effects of education in AD.

PMID- 18622614
TI  - Efficacy of aspiration and autogenous bone marrow injection in the treatment of
      simple bone cysts.
AB  - Twenty eight patients with simple bone cyst that were treated by aspiration and
      percutaneous autogenous bone marrow injection were reviewed to evaluate the
      treatment outcome. There were 18 boys and ten girls. Their mean age was 10.9 +/-
      2.75 years. Single injection was performed for 16 patients; the rest had double
      or triple injections. There were no operative complications. The mean follow-up
      was 34.7 +/- 6.87 months. The procedure succeeded in obtaining healing in 23
      cysts (82%). Cysts with index of more than five and cortical thickness of less
      than 1 mm were significantly prone to pathological fractures and had significant
      poor results after treatment. Our results suggested that autogenous bone marrow
      injection is a safe and effective treatment method for simple bone cysts, but
      sometimes repeated injections are necessary. Cyst index and cortical thickness
      are good indicators for cyst aggressiveness and good predictors for treatment
      outcome.

PMID- 18622615
TI  - Targeting superoxide dismutase 1 to overcome cisplatin resistance in human
      ovarian cancer.
AB  - PURPOSE: Clinical drug resistance to platinum-based chemotherapy is considered a
      major impediment in the treatment of human ovarian cancer. Multiple pathways
      associated with drug resistance have been suggested by many previous studies.
      Over expression of several key proteins involved in DNA repair, drug transport,
      redox regulation, and apoptosis has been recently reported by our group using a
      global quantitative proteomic profiling approach. Superoxide dismutase 1 (SOD1)
      is one of these proteins consistently over-expressed in cisplatin-resistant
      ovarian cancer cells as compared to their sensitive counterparts, but its precise
      role in drug resistance is yet to be defined. METHOD: In the current study, we
      examined the role of SOD1 in drug resistance by inhibiting its redox activity in
      cisplatin-resistant ovarian cancer cells using a small-molecule inhibitor,
      triethylenetetramine (TETA). The effect of TETA was determined by the cell
      proliferation assay, clonogenic cell survival assay, and SOD1 activity assay.
      RESULTS: The inhibition of the SOD1 activity enhanced the cisplatin sensitivity
      in the resistant cells supporting the hypothesis that SOD1 is a key determinant
      of cisplatin resistance and is an exploitable target to overcome cisplatin drug
      resistance. CONCLUSION: SOD1 plays an important role in cisplatin resistance and
      modulation of its activity may overcome this resistance and ultimately lead to
      improved clinical outcomes.

PMID- 18622616
TI  - Expression of the rDNA-encoded mitochondrial protein Tar1p is stringently
      controlled and responds differentially to mitochondrial respiratory demand and
      dysfunction.
AB  - The novel yeast protein Tar1p is encoded on the anti-sense strand of the multi
      copy nuclear 25S rRNA gene, localizes to mitochondria, and partially suppresses
      the mitochondrial RNA polymerase mutant, rpo41-R129D. However, the function of
      Tar1p in mitochondria and how its expression is regulated are currently unknown.
      Here we report that Tar1p is subject to glucose repression and is up-regulated
      during post-diauxic shift in glucose medium and in glycerol medium, conditions
      requiring elevated mitochondrial respiration. However, Tar1p expression is down
      regulated in response to mitochondrial dysfunction caused by the rpo41-R129D
      mutation or in strains lacking respiration. Furthermore, in contrast to the
      previously reported beneficial effects of moderate over-expression of Tar1p in
      the rpo41-R129D strain, higher-level over-expression exacerbates the ROS-derived
      phenotypes of this mutant, including decreased respiration and life span.
      Finally, two-hybrid screening and in vitro-binding studies revealed a physical
      interaction between Tar1p and Coq5p, an enzyme involved in synthesizing the
      mitochondrial electron carrier and antioxidant, coenzyme Q. We propose that Tar1p
      expression is induced under respiratory conditions to maintain oxidative
      phosphorylation capacity, but that its levels in mitochondria are typically low
      and stringently controlled. Furthermore, we speculate that Tar1p is down
      regulated when respiration is defective to prevent deleterious ROS-dependent
      consequences of mitochondrial dysfunction.

PMID- 18622618
TI  - [Ipsilateral autorotational keratoplasty and cataract extraction in patients with
      trachoma and trauma in Oman. Report on visual rehabilitation].
AB  - AIM: To report on the results of visual rehabilitation by ipsilateral rotational
      keratoplasty (IRK) and cataract extraction in 17 patients with trachoma and with
      trachoma and trauma in Oman over 3 years. PATIENTS: Of 25 patients operated from
      2001-2004 with IRK, extracapsular cataract extraction, and intraocular lens
      implantation, 17 eyes of 17 patients with cicatricial trachoma (WHO stage CO)
      could be followed up after 1 year. Group 1 comprised 11 eyes with ciatricial
      trachoma. In group 2, six eyes had additional traumatic corneal scars. METHODS:
      Surgery was performed using a motor trephine Keratron (Geuder), the Accurus 800
      (Alcon) phacovitrectomy machine, and calculation for intraocular lens
      implantation (IOL: MZ60BD, Alcon) with a topography (Atlas, Humphrey Zeiss)
      supported SRK II formula (OcuScanRxP, Alcon). RESULTS: Although only four of 17
      patients had preoperative visual acuity (VA) at 5 m and one of 17 had VA at 1 m,
      postoperatively seven of 17 patients gained VA at 5 m and six of 17 at 1 m.
      Ambulatory vision was regained in 13 of 17 (78%) patients. Patients with trachoma
      and trauma benefited more from the surgery [vision increase in trachoma: eight of
      11 eyes (73%); trachoma and trauma: five of five eyes (100%)]. Postoperative
      spherical refraction was -12.0D to +4.0D (median:+4.0D), and astigmatism ranged
      from 10D to 0.3D (median 5.35D). One eye was lost because of uncontrolled
      keratitis. CONCLUSIONS: IRK with cataract extraction may provide ambulatory
      vision in patients with cicatricial trachoma and secondary dry eye syndrome
      living in developing countries where donor grafts are difficult to obtain and
      where postoperative follow-up of high-risk keratoplasty is impaired.

PMID- 18622617
TI  - Pseudohyphal differentiation defect due to mutations in GPCR and ammonium
      signaling is suppressed by low glucose concentration: a possible integrated role
      for carbon and nitrogen limitation.
AB  - In response to carbon and/or nitrogen limitation, diploid cells of Saccharomyces
      cerevisiae either sporulate or develop pseudohyphae. Although the signal
      transduction pathways leading to these developmental changes have been
      extensively studied, how nutritional signals are integrated is not clearly
      understood. Results of this study indicate that reducing glucose concentration
      from 2% (SLAD) to 0.05% (SLALD) causes an increase in the magnitude of
      filamentation as well as a discernible reduction in the time required for
      pseudohyphal development. Further, the pseudohyphal defect of gpa2, gpr1and
      gpa2gpr1 but not the mep2 mutant strain is overcome on SLALD. Low glucose also
      induced pseudohyphae in mep2gpr1 but not mep2gpa2 strain suggesting that GPR1
      inhibits pseudohyphae by inhibiting GPA2 function. Accordingly, deleting GPA2 in
      mep2gpr1 mutant abrogated pseudohyphae formation in SLALD. Further, replenishment
      of glucose suppressed pseudohyphal differentiation in wild-type cells grown in
      SLAD medium. However, in SLALD, glucose replenishment suppressed the
      filamentation response of gpa2 mutants but not that of strains carrying the wild
      type GPA2. Increased trehalose levels correlated with decreased pseudohyphae
      formation. Results of this study demonstrate that filamentation in response to
      nitrogen limitation occurs as glucose becomes limiting.

PMID- 18622619
TI  - Intraoperative infrared brain surface blood flow monitoring during superficial
      temporal artery-middle cerebral artery anastomosis in patients with childhood
      moyamoya disease.
AB  - OBJECTIVE: To monitor patency of the bypass and to accomplish comprehensive
      visualized evaluation of brain surface hemodynamics in childhood moyamoya
      patients, we performed intraoperative monitoring using novel infrared imaging
      system. MATERIALS AND METHODS: Intraoperative monitoring of brain surface blood
      flow by IRIS V infrared imaging system has been conducted during superficial
      temporal artery-middle cerebral artery anastomosis on seven sides of five
      pediatric patients with moyamoya disease (man/woman = 2:3, 7-8 years old). The
      range of recipient artery was 0.7-0.8 mm (average 0.75 mm). Magnetic resonance
      imaging and magnetic resonance angiography were performed routinely before and
      after surgery. CONCLUSIONS: In all cases, patency of bypass, as well as detailed
      local hemodynamics and changes of brain surface temperature distribution could be
      evaluated. Intraoperative infrared system will be a feasible monitoring not only
      for noninvasive intraoperative evaluation of bypass patency but also for local
      hemodynamics even in patients with childhood moyamoya disease.

PMID- 18622621
TI  - Disappearance of a middle cerebral artery aneurysm associated with Moyamoya
      syndrome after revascularization in a child: case report.
AB  - INTRODUCTION: Pediatric Moyamoya disease is rarely associated with intracranial
      aneurysms. We report a case of a 7-year-old girl with an antecedent of persistent
      craniopharyngeal canal, who presented with a history of choreiform movements.
      MATERIALS AND METHODS: A Moyamoya disease was found with an unruptured left
      middle cerebral artery aneurysm on her first angiography. Conservative treatment
      was chosen for the aneurysm and she underwent indirect revascularization by
      encephalosynangiosis using the multiple bur-hole technique for her Moyamoya
      disease. Abnormal movements were improved. Control angiogram at 6 months showed
      development of intracranial-extracranial anastomoses with complete resolution of
      the aneurysm. Aneuryms including the major arteries of the basal arterial circle
      occur as a by-product of the high velocity and blood flow secondary to the
      arterial stenosis. Blood flow modification after revascularization often lead to
      spontaneous regression and disappearance of these aneurysms. CONCLUSION:
      Therefore, a conservative treatment of these proximal aneurysms must be chosen
      after encephalosynangiosis.

PMID- 18622620
TI  - Resolution of syringomyelia and Chiari malformation after growth hormone therapy.
AB  - INTRODUCTION: The association between hypopituitarism, Chiari I malformation, and
      syringomyelia has been recently recognized. Most of the reported patients
      suffered perinatal injury or asphyxia. MATERIALS AND METHODS: We present the case
      of a premature child without identifiable perinatal injury, who was recognized to
      have growth hormone (GH) deficiency, Chiari I malformation, and
      syringohydromyelia. CONCLUSION: There was a resolution of syrinx and tonsillar
      herniation after GH replacement.

PMID- 18622622
TI  - Distal lengthening of ilio-tibial band by Z-plasty for treating refractory
      greater trochanteric pain after total hip arthroplasty (Pedersen-Noor operation).
AB  - INTRODUCTION: The development of greater trochanteric pain (GTP) after total hip
      arthroplasty (THA) represents a special category. Despite that treatment is
      mainly conservative, some patients show poor response and surgical intervention
      should be considered. We propose a new method consisting of distal lengthening of
      ilio-tibial band (ITB) by Z-plasty. MATERIAL AND METHODS: Between March 2004 and
      June 2006, 12 women with refractory GTP after THA were operated on using distal
      ITB lengthening. The procedure was done under local anaesthesia on an outpatient
      basis. The patients were followed up 3-4 months postoperatively by phone
      interview and at 1-3 years by EQ-5D questionnaire and clinical examination
      including tenderness evaluation with algometer. RESULTS: All patients improved
      significantly (EQ-5D = 0.26 preoperatively vs. 0.67 postoperatively; P < 0.005)
      except one patient who experienced no change in GTP symptoms. No postoperative
      complications were reported. CONCLUSION: We believe that treating patients with
      GTP after THA by the technique described offers a simple, safe and reliable
      method.

PMID- 18622623
TI  - Detection of the A189G mtDNA heteroplasmic mutation in relation to age in modern
      and ancient bones.
AB  - The aim of this study was to demonstrate the presence of the A189G age-related
      point mutation on DNA extracted from bone. For this, a peptide nucleic acid
      (PNA)/DNA sequencing method which can determine an age threshold for the
      appearance of the mutation was used. Initially, work was done in muscle tissue in
      order to evaluate the sensitivity of the technique and afterwards in bone samples
      from the same individuals. This method was also applied to ancient bones from six
      well-preserved skeletal remains. The mutation was invariably found in muscle, and
      at a rate of up to 20% in individuals over 60 years old. In modern bones, the
      mutation was detected in individuals aged 38 years old or more, at a rate of up
      to 1%, but its occurrence was not systematic (only four out of ten of the
      individuals over 50 years old carried the heteroplasmy). For ancient bones, the
      mutation was also found in the oldest individuals according to osteologic
      markers. The study of this type of age-related mutation and a more complete
      understanding of its manifestation has potentially useful applications. Combined
      with traditional age markers, it could improve identification accuracy in
      forensic cases or in anthropological studies of ancient populations.

PMID- 18622624
TI  - Job stress and depressive symptoms among Korean employees: the effects of culture
      on work.
AB  - OBJECTIVE: This study was conducted to investigate the association between
      depressive symptoms and job stress, as measured by the KOSS, among Korean
      employees in small- and medium-sized enterprises, and examined which components
      of stress are involved in the risk for depression among males and females.
      METHODS: Data were collected from a work-stress survey of full-time employees of
      small- and medium-sized enterprises in Incheon, South Korea. A total of 3,013
      participants were included in the analysis. Job stress was measured using 24
      items (7 sub-scales) of the short form of Korean occupational stress scale (KOSS
      SF), and depressive symptoms were evaluated using Center for epidemiologic
      studies depression scale (CES-D). RESULTS: After adjustment for confounding
      variables, most of subscales of job stress contributed to an increased risk of
      depressive symptoms, and job insecurity (male; OR = 2.02, 95%CI: 1.61-2.40,
      female; OR = 1.95, 95%CI: 1.42-2.70) and occupational climate (male; OR = 1.84,
      95%CI: 1.49-2.28, female; OR = 1.78, 95%CI: 1.30-2.49) showed strong associations
      in both male and female. Other subscales revealed different effects for males and
      females; for males, job demands (OR = 1.68, 95%CI: 1.43-2.20), inadequate social
      support (OR = 1.55, 95%CI: 1.23-1.94), and lack of rewards (OR = 1.88, 95%CI:
      1.48-2.37) were associated with depressive symptoms, whereas for females,
      organizational injustice (OR = 1.62, 95%CI: 1.14-2.30) was associated with
      depressive symptoms. CONCLUSION: These results indicate that job stress may play
      a significant role in increasing the risk of depressive symptoms, and that
      further preventive efforts and research are needed to reduce job stress and
      address health problems caused by job stress among Korean employees.

PMID- 18622625
TI  - Identification of genotypes of Giardia intestinalis of human isolates in Egypt.
AB  - In Egypt, the genotyping study of Giardia intestinalis in human is limited. To
      determine the prevalence of G. intestinalis, faecal samples were collected from
      Egypt. Samples were concentrated using density gradient centrifugation. The
      samples were subjected to PCR and DNA sequence analysis for TPI gene. Prevalence
      of Giardia infection was 34.6% of 52 examined. DNA sequence showed that the
      Assemblage B was the most prevalent (80%) genotype, the 15% of the positive
      samples belonged to Assemblage E, and the 5% of them belonged to Assemblage A.
      Certainly, both genotypes A and B are highly common in human worldwide. However,
      up to now, Assemblage E had not been known to be infectious for humans.
      Therefore, this is the first time that Assemblage E is reported in human.
      However, further analyses of a second locus are required to confirm this result.
      The extent to which Giardia-infected cattle in Egypt might pose a risk of human
      infection is unknown.

PMID- 18622626
TI  - Susceptibility of two strains of mice to the infection with Schistosoma mansoni:
      parasitological and biochemical studies.
AB  - In this article, two strains of mice BALB/C and C57 were infected with Egyptian
      strain of Schistosoma mansoni. BALB/C mice appeared to harbor fewer parasites
      than did C57 mice. The hepatic and intestinal tissues of C57 mice were loaded
      with more eggs than that of BALB/C mice. Regardless the strain of mice, the
      number of eggs per gram of liver tissues was higher than in the intestinal
      tissues. Some biochemical parameters were measured in the liver of infected and
      non-infected mice; a significant decrease in the activities of alkaline
      phosphatase, catalase, glutathione-s-transferase, glutathione, and total lipids
      of infected mice compared to their matched control were observed. However, there
      was a significant increase in malondialdehyde level of infected mice compared to
      their matched group. Detailed discussion on the parasitological and biochemical
      differences between the two strains was presented.

PMID- 18622627
TI  - Molecular characterization of a calcium-binding protein SjCa8 from Schistosoma
      japonicum.
AB  - A full-length cDNA encoding a cercarial stage-specifically expressed 8-kDa
      calcium-binding protein (SjCa8) was isolated from Schistosoma japonicum cercarial
      cDNA library using microarray screen. The putative gene coding for SjCa8 is of
      371 bp with an open reading frame of 69 amino acid (aa). The deduced aa sequence
      showed 83% identity with the Schistosoma mansoni 8-kDa CaBP, 47% identity with
      Clonorchis sinensis calcium-binding protein, and 38% identity with Fasciola
      hepatica putative calcium-binding protein. Also, it shares more than 30% identity
      with the calmodulin of many different species, while the most significant
      similarity between them lies around the two calcium-binding loop regions. There
      are two potential sites for phosphorylation and one potential site for N
      myristoylation in the sequence. The SjCa8 has also been predicted to contain a
      single pair of EF-hand Ca2+-binding domain. The recombinant SjCa8 (rSjCa8)
      protein expressed and purified from E. coli has been demonstrated to possess the
      calcium-binding activity. Immune serum from UV-attenuated S. japonicum cercariae
      immunized rabbit detected rSjCa8 by Western blot assay, while the sera from S.
      japonicum naturally infected rabbit and normal rabbit could not. These findings
      may contribute to the development of an effective vaccine against
      schistosomiasis.

PMID- 18622628
TI  - Molecular characterization of Trypanosoma cruzi sylvatic isolates from Rio de
      Janeiro, Brazil.
AB  - Trypanosoma cruzi, the etiologic agent of Chagas disease, presents considerable
      heterogeneity between isolated populations within the wild and domestic cycles.
      By using multiplex polymerase chain reaction based on the mini-exon gene,
      characterization was performed on seven samples isolated from specimens of
      Triatoma vitticeps that had been collected from the locality of Triunfo in the
      municipality of Santa Maria Madalena, state of Rio de Janeiro, Brazil. The
      samples SMM10, SMM53, SMM88, and SMM98 (area A) and SMM36 and SMM82 (area B)
      revealed the presence of 150 base pairs, corresponding to the zymodeme III (Z3).
      Our study suggested that one isolate (SMM1) presents a mixed genotype associated
      with Z3 and TcII. The typing of isolates of T. cruzi has the main aim of
      identifying strains with different epidemiological and/or clinical
      characteristics of Chagas disease. Our results corroborate other descriptions in
      the literature and contribute towards the knowledge and records of the profile of
      some additional wild isolates of T. cruzi in regions not yet affected by the
      disease.

PMID- 18622629
TI  - Limits to genetic bottlenecks and founder events imposed by the Allee effect.
AB  - The Allee effect can result in a negative population growth rate at low
      population density. Consequently, populations below a minimum (critical) density
      are unlikely to persist. A lower limit on population size should constrain the
      loss of genetic variability due to genetic drift during population bottlenecks or
      founder events. We explored this phenomenon by modeling changes in genetic
      variability and differentiation during simulated bottlenecks of the alpine
      copepod, Hesperodiaptomus shoshone. Lake surveys, whole-lake re-introduction
      experiments and model calculations all indicate that H. shoshone should be
      unlikely to establish or persist at densities less than 0.5-5 individuals m(-3).
      We estimated the corresponding range in minimum effective population size using
      the distribution of habitat (lake) sizes in nature and used these values to model
      the expected heterozygosity, allelic richness and genetic differentiation
      resulting from population bottlenecks. We found that during realistic bottlenecks
      or founder events, >90% of H. shoshone populations in the Sierra Nevada may be
      resistant to significant changes in heterozygosity or genetic distance, and 70
      75% of populations may lose <10% of allelic richness. We suggest that ecological
      constraints on minimum population size be considered when using genetic markers
      to estimate historical population dynamics.

PMID- 18622630
TI  - Foreign ant queens are accepted but produce fewer offspring.
AB  - Understanding social evolution requires us to understand the processes regulating
      the number of breeders within social groups and how they partition reproduction.
      Queens in polygynous (multiple queens per colony) ants often seek adoption in
      established colonies instead of founding a new colony independently. This mode of
      dispersal leads to potential conflicts, as kin selection theory predicts that
      resident workers should favour nestmate queens over foreign queens. Here we
      compared the survival of foreign and resident queens as well as their relative
      reproductive share. We used the ant Formica exsecta to construct colonies
      consisting of one queen with workers related to this resident queen and
      introduced a foreign queen. We found that the survival of foreign queens did not
      differ from that of resident queens over a period of 136 days. However, the
      genetic analyses revealed that resident queens produced a 1.5-fold higher number
      of offspring than introduced queens, and had an equal or higher share in 80% of
      the colonies. These data indicate that some discrimination can occur against
      dispersing individuals and that dispersal can thus have costs in terms of direct
      reproduction for dispersing queens.

PMID- 18622631
TI  - Neonatal onset of nephrogenic syndrome of inappropriate antidiuresis.
AB  - This paper describes the manifestation in a child of a new syndrome characterized
      by unusual, severe, persistent hyponatremia associated with hyposmolarity,
      euvolemia, inappropriately concentrated urine and elevated natriuresis. This is
      the fourth case of this syndrome reported to date, and the first to be reported
      in a neonate. The clinical features resemble those typically observed in patients
      with inappropriate antidiuretic hormone secretion, although high arginine
      vasopressin (AVP) levels are lacking. The findings led the authors to hypothesise
      a nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The previously
      described R137C gain-of-function mutation was detected by means of mutation
      analysis of the V2R gene. Our results indicate that NSIAD is already present
      during the neonatal period and that molecular analysis of the V2R receptor should
      therefore be carried out, in all newborns with prolonged euvolemic hyponatremia
      with hypo-osmolarity, high urinary sodium and normal/low or undetectable AVP
      levels.

PMID- 18622632
TI  - Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic
      syndrome.
AB  - We performed a multi-centre randomized controlled trial to compare the efficacy
      of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating
      children with frequently relapsing nephrotic syndrome and biopsy-proven minimal
      change disease. Of the 31 randomized initially selected patients, seven were
      excluded. The remaining 24 children received either MMF 1200 mg/m(2) per day (n =
      12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period. Of the 12
      patients in the MMF group, two discontinued the study medication. Evaluation of
      the changes from the baseline glomerular filtration rate showed an overall
      significant difference in favour of MMF over the treatment period (p = 0.03).
      Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA
      group remained in complete remission during the entire study period. Relapse rate
      in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08).
      None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic
      acid were performed in seven patients. The patient with the lowest area under the
      curve had three relapses within 6 months. In children with frequently relapsing
      minimal change nephrotic syndrome, MMF has a favourable side effect profile
      compared to CsA; however, there is a tendency towards a higher relapse risk in
      patients treated with MMF.

PMID- 18622633
TI  - Morphological-anatomical characterization and identification of Tomentella
      ectomycorrhizas.
AB  - Over the last two decades, much information has been gathered on the
      ectomycorrhizal fungus community composition of plant associations of boreal,
      temperate, and tropical regions. Worldwide, Tomentella ectomycorrhizas (ECM) are
      often common and dominant in the mycorrhizosphere of coniferous and deciduous
      forests. They are present under different environmental conditions and associate
      with diverse plant hosts. Tomentella sporocarps, however, are rarely found
      aboveground, so Tomentella species are often missing from fungus community
      studies based on fruit-body presence. Tomentella is a resupinate genus of
      Thelephoraceae (Basidiomycota) forming black-brown, brown, yellow, or ochre ECM
      on the roots of gymnosperm and angiosperm trees, distinguished by typical
      morphological-anatomical characteristics (clamped hyphae, angular mantle, surface
      network, special rhizomorphs and cystidia). In this paper, we review the
      taxonomic position and morphological-anatomical characteristics of Tomentella
      ECM. A short summary of the microscopic features used for distinguishing
      tomentelloids during morphotyping and identification is presented in order to
      support molecular and ecological studies of ectomycorrhizal fungus communities.

PMID- 18622635
TI  - Experimental research on recolonisation with Anemone nemorosa of the beech
      forests of the Ruhr district (Germany) floristically impoverished by air
      pollution.
AB  - BACKGROUND, AIM, AND SCOPE: High SO(2) concentrations as have been observed over
      decades in the Ruhr district lead to a remarkable reduction of leaf area in the
      majority of the characteristic broad-leafed herbs of the Central European beech
      forests even after only a few months of experimental fumigation. Thus, it is no
      wonder in the time of high SO(2) pollution, e.g., in the town of Herne (centre of
      the Ruhr district), that there was not a single beech forest hosting, for
      instance, Viola reichenbachiana or Anemone nemorosa. As air quality has improved
      very much over some decades in the Ruhr district, one can expect a recolonisation
      of the beech forests by the species of former time characteristic for the herb
      layer. However, one has to consider that only the air pollution was reduced,
      while soil acidification and contamination with heavy metals and PAH are, on the
      short run, irreversible. That is why experiments were carried out, considering
      the question as to whether recolonisation of the forests of the Ruhr district by
      the aforementioned species is possible and why such a recolonisation up to now
      has not occurred. MATERIALS AND METHODS: The experiments were carried out in a
      beech forest situated in the centre of the Ruhr district in the City of Herne.
      The wood anemone (A. nemorosa) was chosen as test plant because of its high
      frequency in beech forests on loess soils outside the Ruhr district, and its
      absence in beech forests in the Ruhr district. The experiments with A. nemorosa
      were carried out in three variants with different soils: (a): soil of the local
      forests (R); (b): soil of the local forests whose soot layer was removed (r);
      (c): imported soil from a clean air region far away from the Ruhr district
      (Odenwald). RESULTS: Survival of rhizomes of A. nemorosa is possible for some
      years in the soils of the Ruhr district; however, the establishment of a
      population could not be achieved. The results obtained by the imported soil show
      that it is no longer air pollution, but the soil which prevents the establishment
      of a population. Sexual reproduction is rather impossible because of the thick
      litter layer with which all of the Ruhr district's beech forests are covered.
      DISCUSSION: With respect to the unfavourable chemistry of the soil of the Ruhr
      district and in consideration of the unfavourable attributes of the soot layer,
      the author expected the following order of the development of shoot numbers: O >
      r > R. However, the result is: O > R > r. In contrast to the expected result, the
      soot layer has no negative but slightly positive effects on the implanted
      rhizomes. A possible explanation is that the soot layer, which is situated
      immediately below the top soil, prevents the top soil from drying up and thus
      even protects the rhizomes from desiccation. Also, the possibility has to be
      considered that the soot layer functions as a nutrient storage area. CONCLUSIONS:
      At present, a survival of the rhizomes of A. nemorosa in the soils of the Ruhr
      district is temporarily possible but does not lead to the establishment of a
      permanent population. This only can be achieved by additional sexual
      reproduction. However, the thick litter layer present in all beech forests of the
      Ruhr district prevents the establishment of seedlings, i.e., it does not allow
      sexual reproduction to contribute to the population. The soot layer situated
      below the litter layer represents a second hindrance for germination. Other than
      seedlings, rhizomes are not negatively affected by the soot layer but even a
      slight stabilisation has to be stated. As a reason for this slightly positive
      effect, a protection of the upper mineral soil from desiccation by the hydrophob
      soot layer has to be considered. Secondly, the soot layer may serve as a nutrient
      storage which is of particular importance in acid soils, because acidification
      generally leads to a leeching of nutrients. To answer these questions, detailed
      further research is necessary. RECOMMENDATIONS AND PERSPECTIVES: In order to
      restore the formerly rich herbaceous layer of the forests of the Ruhr district,
      experiments (removal of the litter layer; liming; ploughing) should be carried
      out at broad-scale to solve the question of how the strong negative effects of
      the established thick raw humus layer can be reduced or even be avoided. When the
      problem of the humus layer is solved, the beech forests of the Ruhr district
      today highly impoverished in species will become a vivid ecosystem, rich in
      flowering herbaceous species and thus much more attractive for the people of the
      Ruhr district than at present.

PMID- 18622634
TI  - Delayed perforation of the aorta by a thoracic pedicle screw.
AB  - Pedicle screw instrumentation has become increasingly popular during the past 20
      years and a vast selection of products is available on the market. With rising
      implantation rates, reports about specific complications also have increased. The
      main reason for these complications is the fact that the course of the pedicle
      and in turn the positioning of the pedicle screw cannot be adequately controlled
      visually. Based on the anatomy of the surrounding structures, complications
      caused by malpositioning can be divided into three main groups: mechanical,
      neurological and vascular. Beyond mechanical limitations of spinal motion, nerve
      injury can lead to neurological problems while injuries to vascular structures
      usually cause hemorrhage. These typical problems in general become apparent
      intraoperatively or in the immediate postoperative course. We report on a rare
      delayed complication and analyze the factors that led to it. In addition, we
      outline our treatment strategy. The goal has to be to avoid such problems in the
      future by using suitable navigational aids.

PMID- 18622636
TI  - Comparative activities of daidzein metabolites, equol and O-desmethylangolensin,
      on bone mineral density and lipid metabolism in ovariectomized mice and in
      osteoclast cell cultures.
AB  - Daidzein, a major isoflavone predominantly found in soybean, is mainly
      metabolized to equol and O-desmethylangolensin (O-DMA) by the human gut
      microflora. Equol exhibits a stronger estrogenic activity than daidzein, however,
      only approximately 30% of the population has been identified as equol-producers
      and there are too few direct evidences of the effects of the other major
      metabolite, O-DMA on estrogen-deficient status. The purpose of this study is
      therefore, to compare the effect of both O-DMA and equol on bone and lipid
      metabolism in vivo and in vitro. For the in vivo study, 8-week-old female mice
      were assigned to five groups as follows: sham-operated (sham), ovariectomized
      (OVX), OVX + 0.5 mg/day O-DMA (OVX + O-DMA), OVX + 0.5 mg/day equol (OVX + Eq),
      and OVX + 0.03 microg/day 17beta-estradiol (OVX + E2) administration. Three weeks
      after the intervention, O-DMA and equol did not affect uterine atrophy in OVX
      mice. The bone mineral density (BMD) of the femur was lower in the OVX group than
      in the sham group. The administration of equol but not O-DMA, maintained BMD
      through the intervention. Values of whole body fat mass and plasma lipids were
      lower in the equol and O-DMA treated OVX mice than those in OVX mice. In the in
      vitro study, equol significantly inhibited the osteoclast formation induced by
      1alpha,25(OH)(2)D(3) in a dose-dependent manner in a co-culture system of mouse
      bone-marrow cells with primary osteoblastic cells. However, O-DMA slightly
      inhibited osteoclast formation, and the effect was not dose dependent. These
      results suggest that the effects of O-DMA on bone and lipid metabolism in OVX
      mice and osteoclast cell cultures are weaker than those of equol.

PMID- 18622637
TI  - Diet diversity and the risk of oral and pharyngeal cancer.
AB  - BACKGROUND: Diet diversity has been recommended to achieve a healthy diet and
      prevent cancer. AIM OF THE STUDY: The relation between diet diversity (i.e.,
      variety in food intake computed as the total number of foods consumed at least
      once per week) and the risk of oral and pharyngeal cancer was investigated using
      data from a multicentric case-control study carried out between 1991 and 2005 in
      Italy. METHODS: Cases were 805 patients with histologically confirmed incident
      cancers of the oral cavity and pharynx, and controls were 2,081 patients admitted
      for acute, non-neoplastic diseases, unrelated to tobacco or alcohol consumption.
      RESULTS: A significant inverse association was observed with total diet
      diversity. The multivariate odds ratio (OR), adjusted for education, tobacco and
      alcohol, was 0.78 (95% confidence interval, CI 0.61-0.98) for subjects in the
      highest tertile of diversity. Inverse relations were found also for diversity
      within vegetables (OR = 0.62; 95% CI 0.49-0.78) and fruits (OR = 0.67; 95% CI
      0.53-0.86). CONCLUSIONS: This study suggests that a more diversified, and
      particularly a diet varied in vegetables and fruit, is a favourable indicator of
      oral and pharyngeal cancer risk, independently from the major recognised risk
      factors, i.e. alcohol and tobacco consumption.

PMID- 18622638
TI  - Advanced glycation end products depress function of endothelial progenitor cells
      via p38 and ERK 1/2 mitogen-activated protein kinase pathways.
AB  - OBJECTIVE: Advanced glycation end products (AGEs) and endothelial progenitor
      cells (EPCs) play divergent roles in the process of atherosclerosis. We
      investigated the effects of AGE-human serum albumin (AGE-HSA) on receptor
      expression for AGEs (RAGE) and EPCs apoptosis. METHODS: The human mononuclear
      cells were obtained by Ficoll density gradient centrifugation and cultured in
      M199 medium containing rh-VEGF (30 ng/ml), rh-b-FGF(6 ng/ml) and 20% NBCS for 8
      days. The adhesive EPCs were sequentially harvested after 24 h synchronization
      and challenged with AGE-HSA (concentration range from 0 to 300 microg/ml) for 24
      h and 200 microg/ml AGE-HSA (time range from 0 to 36 h). EPCs apoptosis and
      migration were determined, expressions of RAGE, phosphorylated ERK1/2, JNK and
      p38 mitogen-activated protein kinase (MAPK) of EPCs were quantified by
      fluorescent quantitation RT-PCR and Western-blot, effect of AGE-HSA on NF-kappaB
      activtiy was determined by EMSA (electrophoretic mobility shift assay) in the
      presence and absence of special MAPK pathways pathway inhibitors. RESULTS: AGE
      HSA upregulated the expression of RAGE, this effect could be significantly
      inhibited by p38 MAPK and ERK MAPK inhibitor, but not by JNK MAPK inhibitor. AGE
      HSA also promoted EPCs apoptosis and inhibited EPCs migration and increased NF
      kappaB activity, these effects could be significantly attenuated by the anti-RAGE
      neutralizing antibody as well as by p38 and ERK MAPK inhibitors. CONCLUSION: AGE
      HSA could promote atherosclerosis by upregulating EPCs RAGE expressions and
      promoting EPCs apoptosis via p38, ERK MAPK pathways, activation of NF-kappaB
      might also play a role in this process.

PMID- 18622639
TI  - Do effectiveness ("real world") studies on antipsychotics tell us the real truth?
AB  - In recent years, so-called "effectiveness studies" have gained increasing
      importance in the context of evidence-based medicine. These studies supposedly
      follow less restrictive methodological standards than phase III studies in terms
      of patient selection, co-medication and other design issues, and their results
      should therefore be better generalisable than those of phase III studies.
      Effectiveness studies, like other types of phase IV studies, can therefore
      contribute to the knowledge about antipsychotics or other psychopharmaceuticals
      and supply relevant information in addition to that gained from phase III trials.
      However, the less restrictive design and inherent methodological problems of
      phase IV studies mean that their results cannot falsify the results of phase III
      studies. The greater complexity of phase IV studies, for example the greater
      variance caused by the different kinds of confounders, means that their results
      have to be interpreted with great care and especially with a high degree of
      awareness of problematic design issues, such as insensitive primary outcome
      criteria, biased randomisation, unblinded treatment conditions, inclusion of
      chronic refractory patients, etc. Some recently published effectiveness studies
      on antipsychotic treatment of schizophrenia will be discussed under these
      methodological aspects. The main conclusions of these trials will be questioned
      on the basis of their severe methodological pitfalls.

PMID- 18622641
TI  - Letter to the editor re: "Optimizing the use of computer radiography in pediatric
      chest imaging".

PMID- 18622640
TI  - Pilot study of pyridostigmine in constipated patients with autonomic neuropathy.
AB  - BACKGROUND: The effects of cholinesterase inhibitors, which increase colonic
      motility in health, on chronic constipation are unknown. Our aims were to
      evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic
      constipation and to assess whether acute effects could predict the long term
      response. METHODS: In this single-blind study, 10 patients with autonomic
      neuropathy and constipation were treated with placebo (2 weeks), followed by an
      escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180-540 mg
      daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and
      8 weeks. The acute effects of neostigmine on colonic transit and motility were
      also assessed. RESULTS: At baseline, 4, 6, and 3 patients had delayed gastric,
      small intestinal, and colonic transit respectively. Pyridostigmine was well
      tolerated in most patients, improved symptoms in 4 patients, and accelerated the
      geometric center for colonic transit at 24 h by > or =0.7 unit in 3 patients. The
      effects of i.v. neostigmine on colonic transit and compliance predicted (P <
      0.05) the effects of pyridostigmine on colonic transit. CONCLUSIONS:
      Pyridostigmine improves colonic transit and symptoms in some patients with
      autonomic neuropathy and constipation. The motor response to neostigmine
      predicted the response to oral pyridostigmine.

PMID- 18622642
TI  - Long-term results of antegrade colonic enema in adult patients: assessment of
      functional results.
AB  - PURPOSE: This retrospective study reviewed long-term results in a large group of
      adult patients treated with antegrade colonic enema and antegrade colonic enema
      combined with a colostomy. METHODS: Retrospective chart review identified 80
      patients (64 females, mean age 51) surgically treated between 1993 and 2007 for
      fecal incontinence or constipation. Surgical treatments included 69
      appendicostomies, 13 tapered ileum, 3 cecal tube, and 25
      appendicostomy/neoappendicostomy combined with a colostomy. A 44-item
      questionnaire was mailed considering bowel regimen, complications, bowel
      function, social function, and quality of life. RESULTS: Sixty-nine patients were
      available for follow-up (mean follow-up, 75 months). Thirty patients (38 percent)
      had surgical complications. Forty-three patients (62 percent) were still
      performing antegrade continence enema and 8 patients (12 percent) no longer
      needed it. Accordingly, treatment was successful in 51 patients (74 percent).
      Twenty-seven patients (63 percent) had side effects. Evaluation of bowel
      function, social function, and quality of life all showed significant
      improvement. Antegrade continence enema was successful in patients with
      neurologic disabilities (67 percent), anorectal injury (53 percent), idiopathic
      fecal incontinence (50 percent), and idiopathic fecal constipation (42 percent).
      Antegrade continence enema was successful in patients with constipation,
      incontinence, and mixed symptoms. Results did not differ between appendicostomy,
      neoappendicostomy, and the combined appendicostomy/neoappendicostomy and
      colostomy. CONCLUSION: Long-term results were favorable in most patients treated
      with antegrade continence enema for fecal incontinence or constipation.

PMID- 18622643
TI  - Does prior abdominal surgery influence conversion rates and outcomes of
      laparoscopic right colectomy in patients with neoplasia?
AB  - PURPOSE: The study investigated the impact of prior abdominal surgery on
      conversions and outcomes of laparoscopic right colectomy. METHODS: A consecutive
      series of 414 patients with cancer or adenomas who underwent a laparoscopic right
      colectomy from March 1996 to November 2006 were studied for surgical conversions
      and outcomes. Conversion was defined as an incision length > 7 cm. RESULTS:
      Patients with prior abdominal surgery (n = 191) were compared with patients with
      no prior abdominal surgery (n = 223), and showed no significant differences in
      age, ASA classification, length of stay, operative time, blood loss, harvested
      nodes, tumor size, and specimen length. Significantly more wound infections
      occurred in the prior abdominal surgery group (22 vs.12, P = 0.023). Body mass
      index > 30 showed a three-fold increased risk of conversion. Fifteen percent of
      the no prior abdominal surgery patients and 17 percent of the prior abdominal
      surgery patients were converted (P > 0.05). Conversion was associated with a
      longer mean length of stay (8.8 days) relative to laparoscopically completed
      cases (6.3 days) regardless of prior abdominal surgery history (P < 0.0001).
      CONCLUSIONS: Laparoscopic right colectomy for neoplasia was not associated with a
      higher conversion rate or morbidity in patients with prior abdominal surgery.
      Prior abdominal surgery is not a contraindication to laparoscopic right
      colectomy.

PMID- 18622644
TI  - Role of surgeon-performed ultrasound in predicting malignancy in patients with
      indeterminate thyroid nodules.
AB  - BACKGROUND: Certain ultrasound features can predict malignancy in patients with
      thyroid nodules. The purpose of this study was to determine the value of surgeon
      performed ultrasound (SUS) in predicting thyroid malignancy in patients with
      indeterminate fine-needle aspiration (FNA) cytology. METHODS: 477 consecutive
      patients with dominant thyroid nodules were referred to our institution from 2002
      to 2007. Of these, 180/477(38%) were judged to have indeterminate cytology:
      follicular neoplasm (FN, n = 108), Hurthle neoplasm (HN, n = 29), and suspicious
      for papillary thyroid cancer (SPTC, n = 43). SUS characteristics for thyroid
      nodules were recorded in a prospective database prior to thyroidectomy. Variables
      analyzed included patients' age and sex, nodule size, shape, echogenicity,
      consistency, borders, multiplicity/multicentricity, and presence of
      microcalcifications. SUS features of thyroid nodules were correlated with final
      pathology. The accuracy of individual SUS features as well as the presence of two
      or more adverse features in predicting malignancy was also examined. RESULTS:
      There were 144 females and 36 males. Mean age was 52 years (range 17-87 years).
      Mean tumor size was 2.7 cm (range 0.65-6.6 cm). Overall, final pathology revealed
      cancer in 92/180 (51%) patients. Malignancy was present in 40/108 (37%) FN, 12/29
      (41%) HN, and 40/43 (93%) SPTC. Nodule borders (irregular), shape (height >
      width), hypoechogenicity, and presence of microcalcifications were significantly
      associated with malignancy. The presence of 2 or >/=3 adverse SUS thyroid nodule
      features was associated with a >/=55% or >/=78% risk of malignancy, respectively.
      CONCLUSION: Adverse thyroid nodule features seen on SUS may predict malignancy
      and help determine the initial extent of thyroidectomy in patients with
      indeterminate FNA cytology.

PMID- 18622645
TI  - Chromosomal alterations associated with the transition from in situ to invasive
      breast cancer.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) is a preinvasive lesion of the breast
      with an inherent but nonobligatory tendency for progression to invasive breast
      cancer. Although the transition from in situ to invasive disease is critical to
      the development of breast cancer, molecular and biological changes responsible
      for this transition are not well characterized. METHODS: Chromosomal alterations
      at 26 regions were assayed in 66 DCIS lesions and 111 invasive ductal carcinomas.
      Levels and patterns of allelic imbalance (AI) were compared between grade 1 DCIS
      and well-differentiated breast carcinomas, and between grade 3 DCIS and poorly
      differentiated invasive breast carcinomas, using Fisher's exact and Student's t
      tests. RESULTS: Levels of AI were significantly lower (P < 0.01) in grade 1 DCIS
      (11.9%) compared to well-differentiated carcinomas (19.2%), but were not
      significantly different between grade 3 DCIS and poorly differentiated tumors. No
      significant differences were detected at any of the 26 chromosomal regions
      between low-grade DCIS and invasive tumors; however, AI events at chromosomes
      1p36, 11q23, and 16q11-q22 could discriminate high-grade in situ from invasive
      disease. CONCLUSION: Lower levels of AI in low-grade in situ compared with
      invasive disease may reflect the protracted time to progression associated with
      low-grade DCIS. Increased levels of AI at chromosomes 1p36 and 11q23 in poorly
      differentiated carcinomas may harbor genes associated with invasiveness, while
      loss of chromosome 16q11-q22 may prevent the transition from in situ to invasive
      disease. Further characterization of these changes may provide molecular assays
      to identify DCIS lesions with invasive potential as well as targets for molecular
      therapeutics.

PMID- 18622646
TI  - Mechanisms driving local breast cancer recurrence in a model of breast-conserving
      surgery.
AB  - OBJECTIVE: We aimed to identify mechanisms driving local recurrence in a model of
      breast-conserving surgery (BCS) for breast cancer. BACKGROUND: Breast cancer
      recurrence after BCS remains a clinically significant, but poorly understood
      problem. We have previously reported that recurrent colorectal tumours
      demonstrate altered growth dynamics, increased metastatic burden and resistance
      to apoptosis, mediated by upregulation of phosphoinositide-3-kinase/Akt
      (PI3K/Akt). We investigated whether similar characteristics were evident in a
      model of locally recurrent breast cancer. METHODS: Tumours were generated by
      orthotopic inoculation of 4T1 cells in two groups of female Balb/c mice and
      cytoreductive surgery performed when mean tumour size was above 150 mm(3). Local
      recurrence was observed and gene expression was examined using Affymetrix
      GeneChips in primary and recurrent tumours. Differential expression was confirmed
      with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation
      of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein
      (HSP)-loaded dendritic cell vaccine was administered in the perioperative period.
      RESULTS: We observed a significant difference in the recurrent 4T1 tumour volume
      and growth rate (p < 0.05). Gene expression studies suggested roles for the
      PI3K/Akt system and local immunosuppression driving the altered growth kinetics.
      We demonstrated that perioperative vaccination with an ex vivo HSP-loaded
      dendritic cell vaccine abrogated recurrent tumour growth in vivo (p = 0.003 at
      day 15). CONCLUSION: Investigating therapies which target tumour survival
      pathways such as PI3K/Akt and boost immune surveillance in the perioperative
      period may be useful adjuncts to contemporary breast cancer treatment.

PMID- 18622647
TI  - Is there a difference in survival between right- versus left-sided colon cancers?
AB  - BACKGROUND: The incidence of right-sided colon cancers has been increasing in
      recent years. It is unclear whether patient prognosis varies by tumor location.
      In this study, we have compared the survival of right-and left-sided colon
      cancers in a longitudinal population-based database. METHODS: A retrospective
      survival analysis was performed using the Surveillance, Epidemiology, and End
      Results Program (SEER) database between 1988 and 2003 on subjects who underwent
      surgical resection for the a primary diagnosis of pathologically confirmed
      invasive colon adenocarcinoma. Cox proportional hazard regression analysis was
      used to assess long-term survival outcomes comparing right-sided (cecum to
      transverse colon, excluding appendix) versus left-sided (splenic flexure to
      sigmoid, excluding rectum) colon cancers. RESULTS: A total of 77,978 subjects
      were identified with adenocarcinoma of the colon. Overall median survival was 83
      months. Median survival for right-sided cancers was 78 vs. 89 months for left
      sided cancers (P < .001). By Cox proportional hazard regression analysis,
      controlling for statistically significant confounders, including age, sex, race,
      marital status, tumor stage, tumor size, histologic grade, number of lymph nodes
      examined, and year of diagnosis, right-sided colon cancers were associated with a
      5% increased mortality risk compared with left-sided colon cancers (hazard ratio,
      1.04; 95% confidence interval, 1.02-1.07). These findings were consistent across
      subsets of subjects. CONCLUSION: On the basis of analysis of information from the
      SEER database, we found that right-sided colon cancers have a worse prognosis
      than left-sided colon cancers. The reason for this remains unclear but may be due
      to biological and/or environmental factors and may have particular bearing, given
      the rising incidence of right-sided colon cancers.

PMID- 18622648
TI  - Clinical value of immunohistochemically detected lymphovascular space invasion in
      early stage cervical carcinoma.
AB  - BACKGROUND: This study investigates the clinical significance of lymphovascular
      space invasion (LVSI) as detected by hematoxylin and eosin (LVSI-H&E) and
      immunohistochemistry (LVSI-IHC) in early stage cervical carcinoma. METHODS:
      Single representative sections from 97 patients with early stage squamous cell
      cervical cancer were immunostained with pancytokeratin and CD31 endothelial cell
      marker antibodies. The H&E sections and their corresponding immunostained
      sections were reexamined to identify LVSI. Associations between LVSI with
      clinicopathological factors were sought. RESULTS: Overall, LVSI was present in 29
      (29.9%) and absent in 68 (70.1%) by IHC, as compared with 18 cases (18.6%) and 79
      cases (81.4%), respectively, by H&E. Statistical analysis revealed a significant
      association between LVSI-H&E and nodal metastasis (P = .004). Follow-up data were
      available for 76 patients. The median follow-up period was 64 months. During
      follow-up, 7 of 24 patients with recurrent disease had evidence of LVSI-H&E as
      opposed to 3 of 52 cases with no recurrence. There was a significant association
      between tumor recurrence and LVSI-H&E (P = .009). The 5-year recurrence-free
      survival was 30% for the group with LVSI-H&E compared with 73% without. There was
      a significant difference in the recurrence-free survival between the two groups
      (P = .002). In contrast LVSI-IHC was found to be associated with no pathological
      factors, and survival analysis revealed no statistically significant association
      with recurrence or survival. CONCLUSION: LVSI-H&E in early stage cervical cancer
      remains an important predictive factor of recurrent disease and reduced disease
      free interval. Immunohistochemically detected LVSI is a common event and seems to
      be of no clinical value.

PMID- 18622649
TI  - 2-Deoxy-2[F-18]FDG-PET for detection of recurrent laryngeal carcinoma after
      radiotherapy: interobserver variability in reporting.
AB  - PURPOSE: To evaluate accuracy and interobserver variability in the assessment of
      2-deoxy-2[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) for
      detection of recurrent laryngeal carcinoma after radiotherapy. PROCEDURES: Eleven
      experienced nuclear physicians from eight centres assessed 30 FDG-PET scans on
      the appearance of local recurrence (negative/equivocal/positive). Conservative
      (equivocal analysed as negative) and sensitive (equivocal analysed as positive)
      assessment strategies were compared to the reference standard (recurrence within
      6months after PET). RESULTS: Seven patients had proven recurrences. For the
      conservative and sensitive strategy, the mean sensitivity was 87% and 97%,
      specificity 81% and 63%, positive predictive values 61% and 46% and negative
      predictive values 96% and 99%, respectively. Interobserver variability showed a
      reasonable relation in comparison to the reference standard (kappa = 0.55).
      CONCLUSIONS: FDG-PET has acceptable interobserver agreement and yields good
      negative predictive value for detection of recurrent laryngeal carcinoma. It
      could therefore be used as first diagnostic step and may reduce futile invasive
      diagnostics.

PMID- 18622650
TI  - Network development in biological gels: role in lymphatic vessel development.
AB  - In this paper, we present a model that explains the prepatterning of lymphatic
      vessel morphology in collagen gels. This model is derived using the theory of two
      phase rubber material due to Flory and coworkers and it consists of two coupled
      fourth order partial differential equations describing the evolution of the
      collagen volume fraction, and the evolution of the proton concentration in a
      collagen implant; as described in experiments of Boardman and Swartz (Circ. Res.
      92, 801-808, 2003). Using linear stability analysis, we find that above a
      critical level of proton concentration, spatial patterns form due to small
      perturbations in the initially uniform steady state. Using a long wavelength
      reduction, we can reduce the two coupled partial differential equations to one
      fourth order equation that is very similar to the Cahn-Hilliard equation;
      however, it has more complex nonlinearities and degeneracies. We present the
      results of numerical simulations and discuss the biological implications of our
      model.

PMID- 18622651
TI  - How do community practitioners decide whether to prescribe antibiotics for acute
      respiratory tract infections?
AB  - BACKGROUND: Overuse of antibiotics in the treatment of acute respiratory tract
      infection (ARI) contributes to the growing problem of antibiotic-resistant
      infections. OBJECTIVE: To identify factors that influence community practitioners
      to prescribe antibiotics and examine how they differ from the recommendations of
      the Centers for Disease Control and Prevention (CDC) guideline for treatment of
      ARI. DESIGN: Paper case vignette study using a fractional factorial design.
      PARTICIPANTS: One hundred one community practitioners and eight faculty members.
      MAIN MEASUREMENTS: We asked community practitioners to estimate how likely they
      would be to prescribe antibiotics in each of 20 cases of ARI and then used
      multiple regression to infer the importance weights of each of nine clinical
      findings. We then compared practitioners' weights with those of a panel of eight
      faculty physicians who evaluated the cases following the CDC guidelines rather
      than their own judgments. MAIN RESULTS: Practitioners prescribed antibiotics in
      44.5% of cases, over twice the percentage treated by the panel using the CDC
      guidelines (20%). In deciding to prescribe antibiotic treatment, practitioners
      gave little or no weight to patient factors such as whether the patients wanted
      antibiotics. Although weighting patterns differed among practitioners, the
      majority (72%) gave the greatest weight to duration of illness. When illness
      duration was short, the rate of prescribing (20.1%) was the same as the rate of
      the faculty panel (20%). CONCLUSIONS: Based on hypothetical cases of ARI,
      community practitioners prescribed antibiotics at twice the rate of faculty
      following CDC practice guidelines. Practitioners were most strongly influenced by
      duration of illness. The effect of duration was strongest when accompanied by
      fever or productive cough, suggesting that these situations would be important
      areas for practitioner education and further clinical studies.

PMID- 18622652
TI  - Laparoscopic bile duct reexploration for retained duct stones.
AB  - BACKGROUND: Failure of endoscopic sphincterotomy (ES) for retained bile duct
      stones occurs in 4% to 10% of cases and was traditionally managed with open bile
      duct reexploration. METHODS: This study uses retrospective analysis of a
      consecutive series of cases of laparoscopic bile duct reexploration for retained
      bile duct stones after unsuccessful ES. RESULTS: Thirty-one cases were operated
      over a 7-year period. Seventy percent had a previous open cholecystectomy. Ten
      cases were successfully treated with a transcystic approach and 19 with
      laparoscopic choledochotomy. Two patients were converted to open surgery.
      Morbidity was 3.22% with no mortality. CONCLUSION: Laparoscopic bile duct
      reexploration can be safely performed and should be considered as an alternative
      to open surgery.

PMID- 18622653
TI  - Mechanical bowel preparation in intestinal surgery: a meta-analysis and review of
      the literature.
AB  - INTRODUCTION: Despite several meta-analyses and randomized controlled trials
      showing no benefit to patients, mechanical bowel preparation (MBP) remains the
      standard of practice for patients undergoing elective colorectal surgery.
      METHODS: We performed a systematic review of the literature of trials that
      prospectively compared MBP with no MBP for patients undergoing elective
      colorectal resection. We searched MEDLINE, LILACS, and SCISEARCH, abstracts of
      pertinent scientific meetings and reference lists for each article found. Experts
      in the field were queried as to knowledge of additional reports. Outcomes
      abstracted were anastomotic leaks and wound infections. Meta-analysis was
      performed using Peto Odds ratio. RESULTS: Of 4,601 patients (13 trials), 2,304
      received MBP (Group 1) and 2,297 did not (Group 2). Anastomotic leaks occurred in
      97(4.2%) patients in Group 1 and in 81(3.5%) patients in Group 2 (Peto OR =
      1.214, CI 95%:0.899-1.64, P = 0.206). Wound infections occurred in 227(9.9%)
      patients in Group 1 and in 201(8.8%) patients in Group 2 (Peto OR = 1.156, CI
      95%:0.946-1.413, P = 0.155). DISCUSSION: This meta-analysis demonstrates that MBP
      provides no benefit to patients undergoing elective colorectal surgery, thus,
      supporting elimination of routine MBP in elective colorectal surgery. CONCLUSION:
      In conclusion, MBP is of no benefit to patients undergoing elective colorectal
      resection and need not be recommended to meet "standard of care."

PMID- 18622654
TI  - Modified puestow lateral pancreaticojejunostomy.
AB  - INTRODUCTION: There are various surgical options for the treatment of pain
      associated with chronic pancreatitis. The modified Puestow lateral
      pancreaticojejunostomy has been proven to be effective in ameliorating symptoms
      and expediting return to normal lifestyle while maintaining a low rate of
      morbidity and mortality. However, the debate regarding which surgical treatment
      provides the best outcomes is controversial. OBJECTIVES: The aims of this
      manuscript are to identify the patient population for which the Puestow benefits
      the most and discuss the pertinent technical aspects of the surgical procedure.

PMID- 18622655
TI  - Portal triad clamping versus vascular exclusion for vascular control during
      hepatic resection: a systematic review and meta-analysis.
AB  - OBJECTIVE: To compare the clinical outcome of patients undergoing liver resection
      under portal triad clamping (PTC) versus hepatic vascular exclusion (HVE).
      METHODS: A systematic literature search was performed following the guidelines of
      the Cochrane collaboration. Randomized controlled trials (RCT) comparing PTC to
      any technique of HVE were eligible for inclusion. Two authors independently
      assessed methodological quality of included trials and extracted data on overall
      morbidity, mortality, cardiopulmonary and hepatic morbidity, intraoperative blood
      loss, transfusion rates, postoperative transaminase and bilirubin levels,
      prothrombin time, and hospital stay. Meta-analyses were performed using a random
      effects model. RESULTS: Of the 1,383 identified references, four RCTs were
      finally included. These trials compared PTC to selective hepatic vascular
      exclusion (SHVE), total hepatic vascular exclusion (THVE), and a modified
      technique of HVE (MTHVE), respectively. Meta-analyses revealed no significant
      difference in morbidity and mortality between PTC and techniques of HVE. Further
      analyses showed significantly reduced overall morbidity for the PTC compared to
      the THVE group. There was a significantly lower transfusion rate for HVE compared
      to PTC. CONCLUSION: Hepatic vascular exclusion does not offer any benefit
      regarding outcome of patients undergoing hepatic resection compared to PTC alone.
      Further, well-designed RCTs evaluating adequate vascular control in major
      hepatectomy and in patients with underlying liver disease appear justified.

PMID- 18622656
TI  - Transnasal fine gastrointestinal fiberscope-guided long tube insertion for
      patients with small bowel obstruction.
AB  - BACKGROUND: The use of a transnasal fine gastrointestinal fiberscope (TNF-GIF)
      has been rapidly disseminating in Japan. However, there has been no trial of long
      tube insertion (LTI) using the TNF-GIF for patients with small bowel obstruction
      (SBO). PURPOSE: To examine whether TNF-GIF-guided LTI is superior to conventional
      LTI for patients with clinically diagnosed SBO. METHODS: The time required for
      LTI was determined prospectively in each group of patients who underwent the
      conventional method (group 1, n = 10) and the TNF-GIF-guided method (group 2, n =
      10) between March 2007 and November 2007. Insertion time was compared between
      groups 1 and 2. RESULTS: Insertion time in group 2 was significantly shorter than
      that in group 1 (group 1, 22 +/- 16 min versus group 2, 9.2 +/- 5.4 min; P =
      0.03). CONCLUSIONS: Novel TNF-GIF-guided LTI is useful and superior to the
      conventional method.

PMID- 18622657
TI  - How I do it: laparoscopic Heller myotomy with Toupet fundoplication for
      achalasia.
AB  - Achalasia, an esophageal motility disorder characterized by aperistalsis and
      failure of lower esophageal sphincter (LES) relaxation, is most effectively
      treated by surgical ablation of the LES. In this report, we describe our
      technique of laparoscopic extended Heller myotomy with Toupet partial posterior
      fundoplication. The technical details of this procedure include careful division
      of the longitudinal and circular muscle fibers of the LES anteriorly, including
      extension of the myotomy 3 cm distal to the esophagogastric junction onto the
      gastric cardia. The Toupet procedure, involving a posterior wrap of the gastric
      fundus which is secured to both edges of the myotomy as well as to the crura of
      the hiatus, is added to prevent post-myotomy gastroesophageal reflux. From a
      recently published report, mean dysphagia scores remained low (3 out of 10
      severity on a visual analog scale) and symptoms of reflux were reported minimally
      in a series of 63 patients followed for a median of 45 months. This technique
      provides excellent and durable relief of dysphagia associated with achalasia
      while minimizing post-myotomy acid reflux symptoms.

PMID- 18622658
TI  - Effect of medical or surgical admission on outcome of patients with gallstone
      pancreatitis and common bile duct stones.
AB  - INTRODUCTION: Management of uncomplicated common bile duct stone (CBDS) and
      gallstone pancreatitis (GP) presumably varies based on whether a patient is
      admitted to medicine or surgery. This study evaluates the impact of admitting
      team on outcome and cost. METHODS: Three hundred seventy patients admitted to the
      Massachusetts General Hospital for CBDS or GP were retrospectively analyzed for
      demographics, insurance status, procedures, complications, length of stay,
      readmission, and cost. A multivariable analysis was conducted for outcome and
      cost measures. RESULTS: Patients admitted to a surgical service were younger than
      those admitted to a medical service. Gender, race, tobacco use, and the presence
      of chronic obstructive pulmonary disease and chronic renal insufficiency were not
      significantly different between groups. Patients admitted to a medical service
      had a higher incidence of coronary artery disease and diabetes. Despite lower
      readmission rates for surgical patients, there was no difference in total
      hospital days between groups. Though total cost of an initial surgical admission
      was greater than a medical admission, total cost attributable to the index
      admission diminished over time and ultimately was not significant in follow-up.
      CONCLUSIONS: Despite variations in uncomplicated management of CBDS and GP, there
      is no difference, in long-term follow-up, in the total number of hospital days or
      cost for the management of CBDS or GP based on admitting team practices.

PMID- 18622659
TI  - Biliary injury after laparoscopic cholecystectomy in a patient with right liver
      agenesis: case report and review of the literature.
AB  - INTRODUCTION: An 87-year-old man underwent attempted laparoscopic
      cholecystectomy. MATERIAL AND METHODS: The procedure was characterized by
      significant inflammation and bleeding requiring conversion to an open procedure.
      Postoperatively, the patient had continued bile drainage from his surgical drain.
      He was referred to our institution and found to have complete transection of his
      common bile duct. Incidentally, he was noted on imaging studies to have absence
      of his right liver with associated left liver hypertrophy. This was characterized
      by complete absence of the right portal vein and right bile duct. Review of his
      preoperative imaging confirmed this finding of right liver agenesis and very
      unusual hepatic vein anatomy. CONCLUSION: This represents the first reported case
      of bile duct injury in the setting of right liver agenesis. We review the details
      of the case and the natural history of agenesis of a hemiliver.

PMID- 18622660
TI  - Long-term outcome of operated and unoperated epiphrenic diverticula.
AB  - INTRODUCTION: The natural history of esophageal epiphrenic diverticula (ED) is
      not entirely clear; the decision whether to operate or not is often based on the
      personal preference of the physician and patient. The aim of this study was to
      evaluate the long-term fate of operated and unoperated patients with ED.
      MATERIALS AND METHODS: Clinical, radiological, and motility findings, and
      operative morbidity and long-term outcome of 41 patients with ED (January 1993 to
      December 2005) were analyzed. All patients were reviewed at the outpatient clinic
      or interviewed over the phone. A symptom score was calculated using a standard
      questionnaire and subjective patient assessment. The radiological maximum
      diameter of the ED was measured. RESULTS: Twenty-two patients (12M:10F; median
      age, 60 years) were operated. One underwent surgery for spontaneous rupture of a
      large diverticulum. Operative mortality was nil; postoperative morbidity was
      22.7%, the most severe complication being suture leakage (4 patients, all managed
      conservatively); median follow-up was 53 months. Nineteen patients (9M, 10F;
      median age 70 years) were not operated: 3 received pneumatic dilations; median
      follow-up was 46 months. None of the patients in either group died for reasons
      related to their ED. Symptoms decreased in all operated patients and, to a lesser
      extent, also in unoperated patients. ED recurrence was observed in one operated
      patient. Four patients had GERD symptoms with esophagitis and/or positive pH
      metry after surgery and 3 patients had persistent dysphagia/regurgitation and
      were dissatisfied with the outcome of surgery. DISCUSSION: Surgery is an
      effective treatment for ED, but carries a significant morbidity related mainly to
      suture leakage. Even in the long-term, unoperated patients do not die of their
      ED, though a better subjective symptom outcome is reported by operated patients.
      A non-interventional policy can safely be adopted in cases of small, mildly
      symptomatic ED.

PMID- 18622661
TI  - Quantitative assessment of hepatic function and its relevance to the liver
      surgeon.
AB  - BACKGROUND: Standard evaluation of patients undergoing hepatic surgery has been
      through radiological and quantitative determination of liver function. As more
      complex and extensive surgery is now being performed, often in the presence of
      cirrhosis/fibrosis or following administration of chemotherapy, it is questioned
      whether additional assessment may be required prior to embarking on such surgery.
      The aim of this review was to determine the current knowledge base in relation to
      the performance of quantitative assessment of hepatic function both pre- and post
      operatively in patients undergoing hepatic resectional surgery and liver
      transplantation. METHODS: An electronic search was performed of the medical
      literature using the MEDLINE database to identify relevant articles with cross
      referencing of all identified papers to ensure full literature capture. RESULTS
      AND CONCLUSIONS: The review has identified a number of different methods of
      dynamically assessing hepatic function, the most frequently performed being
      through the use of indocyanine green clearance. With the recent and further
      anticipated developments in hepatic resectional surgery, it is likely that
      quantitative assessment will become more widely practiced in order to reduce post
      operative hepatic failure and improve outcome.

PMID- 18622662
TI  - Standardization of a colorimetric method to quantify growth and metabolic
      activity of Wolbachia-infected mosquito cells.
AB  - The Aedes albopictus Aa23 cell line, which is persistently infected with
      Wolbachia pipientis strain wAlbB, tends to grow as aggregated clusters of cells
      that are difficult to disperse for conventional quantification based on cell
      number. We used A. albopictus C7-10 cells to validate conversion of
      methylthiazole tetrazolium (MTT) to a colored formazan product with respect to
      incubation time, cell number over a 40-fold range, and metabolic activity as
      cells enter stationary phase. Using this assay, we showed that the doubling time
      of Aa23 cells increases from about 45 h early after plating to more than 70 h as
      the cells reach stationary levels. Growth of Aa23 cells proceeds at similar rates
      in the presence or absence of tetracycline concentrations that decrease the
      abundance of Wolbachia. Insofar as the MTT assay reflects mitochondrial function,
      our results indicate that, in Aa23 cells, abundance of intracellular Wolbachia
      has no measurable effect on mitochondrial activity in the presence of
      tetracycline.

PMID- 18622663
TI  - The role of adherent cells in the immunosuppressed state of mouse progeny
      transplacentally exposed to benzo(alpha)pyrene.
AB  - In recent studies, we showed that murine fetal liver cells from progeny exposed
      to benzo(alpha)pyrene in utero by intraperitoneal injection of the dam at
      midpregnancy (12 d) suppressed cell proliferation in an allogeneic mixed
      lymphocyte response. On the other hand, fetal liver cells from the corn oil
      (vehicle for the carcinogen)-exposed progeny (control) appeared to enhance
      proliferation. Suppression or enhancement appeared to be mediated by fetal liver
      bearing CD8+ and Lyt 1+ (CD5+) cells. Despite these manifestations, the role of
      third-party cells needs to be considered. As a first premise, adherent cells were
      targeted as possible third-party cells. To test the role of the adherent cells,
      liver cells from benzo(alpha)pyrene-exposed fetuses were treated with ficoll
      hypaque, and the interface cells were fractionated through glass wool or nylon
      wool. It is known that adhering cells, macrophages and B cells, readily attach to
      glass or nylon wool. The effluent cells and the adherent cells were cultured with
      syngeneic responder cells and allogeneic stimulator cells in a mixed lymphocyte
      response. The results showed that benzo(alpha)pyrene-effluent cells led to the
      enhancement of proliferation in the mixed lymphocyte response, while
      benzo(alpha)pyrene-adherent cells led to suppression. The effluent and adherent
      cells of corn oil controls did not modify cell proliferation in the mixed
      lymphocyte response. These data suggest that a third-party cell, reasonably the
      macrophage or possibly B cells or both, since these are adherent cells, play a
      decided role in mediating suppression in the benzo(alpha)pyrene-exposed progeny.

PMID- 18622664
TI  - A new Trichoplusia ni cell line for membrane protein expression using a
      baculovirus expression vector system.
AB  - A new cell line, MSU-TnT4 (TnT4), was established from Trichoplusia ni embryos
      for use with baculovirus expression vectors and evaluated for its potential for
      membrane protein production. To evaluate membrane protein synthesis, recombinant
      baculoviruses were constructed to express the human neurotensin receptor 1 as an
      enhanced green fluorescent protein (GFP) fusion. TnT4 cells had a doubling time
      of 21 h and expressed the membrane-GFP fusion protein at approximately twice the
      level as Sf21 cells from the p10 promoter, as evaluated by GFP intensity.
      Expression of secreted alkaline phosphatase (SEAP) was similar to that of Sf21
      cells. Expression of membrane-GFP fusion proteins in recombinant baculoviruses
      provides a rapid method for evaluating the potential of new cell lines for the
      production of membrane proteins using a baculovirus expression vector system
      (BEVS).

PMID- 18622666
TI  - Musculoskeletal trauma services in Serbia.
AB  - Serbia, a middle-income country, is located in southeastern Europe, with
      territory of 88,361 km(2) and 9,400,000 inhabitants. Average month salary is
      US$542 and the registered unemployment rate is 22%. The country is
      administratively divided into 30 districts (193 municipalities). The healthcare
      system is territorially organized. In the state capital there are five clinical
      hospitals with musculoskeletal traumatology departments, as well as one in each
      of the four university centers. In addition, there are orthopaedic departments in
      40 smaller hospitals throughout the country and in three military hospitals,
      along with several pediatric surgical departments involved in managing
      musculoskeletal trauma. There are 524 orthopaedic trauma surgeons (1:18,000
      people), with a minor number of additionally trained general and pediatric
      surgeons who care for musculoskeletal problems. Bonesetters are neither
      recognized nor included in the healthcare system. Orthopaedic traumatology
      services are well organized, with variable accessibility depending on the
      distance between injury site and nearest medical facility. Preventive strategies
      are well developed and mainly consider agricultural, industrial, and traffic
      injuries. Distribution of medical institutions is satisfactory. Future activities
      should include continuing medical education of specialists, exclusion of
      inappropriate specialists, improvement of preventive strategies and medical
      transport facilities, as well as standardization of medical equipment,
      diagnostics, and treatment protocols.

PMID- 18622665
TI  - Radiographic joint space width in patients with Crowe Type-I dysplastic hips.
AB  - Radiographic evaluation of preoperative joint space width is believed important
      to predict the long-term results of osteotomy. We asked whether joint space width
      differs in the supine and standing positions in patients with Crowe Type-1
      osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH). Joint
      space width was measured in the supine and standing positions in 146 women and 16
      men (231 hips) with OA. Subjects had a mean age of 46.7 years (range, 22-59
      years). Differences were seen on radiographs in joint space width between supine
      (2.35 +/- 1.65 mm; range, 0.1-6.2 mm) and standing (2.04 +/- 1.78 mm; range, 0.0
      5.9 mm). In 27 of 172 hips with greater than 1 mm joint space in the supine
      position, joint space width was decreased by greater than 1 mm in the standing
      position. To evaluate preoperative joint space width in patients scheduled for
      osteotomy, radiographs should be obtained with the patient in the standing
      position. LEVEL OF EVIDENCE: Level IV, diagnostic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18622667
TI  - Plant and animal transglutaminases: do similar functions imply similar
      structures?
AB  - In plants the post-translational modification of proteins by polyamines catalysed
      by transglutaminases has been studied since 1987; it was identified by the
      production of glutamyl-polyamine derivatives, biochemical features, recognition
      by animal antibodies and modification of typical animal substrates.
      Transglutaminases are widespread in all plant organs and cell compartments
      studied until now, chloroplast being the most studied. Substrates are:
      photosynthetic complexes and Rubisco in chloroplasts, cytoskeleton and cell wall
      proteins. Roles either specific of plants or in common with animals are related
      to photosynthesis, fertilisation, stresses, senescence and programmed cell death,
      showing that the catalytic function is conserved across the kingdoms. AtPng1p,
      the first plant transglutaminase sequenced shows undetectable sequence homology
      to the animal enzymes, except for the catalytic triad. It is, however, endowed
      with a calcium-dependent activity that allowed us to build a three-dimensional
      model adopting as a template the animal transglutaminase 2.

PMID- 18622668
TI  - Current challenges in the management of invasive fungal infections.
AB  - The incidence of invasive fungal infections (IFIs) has increased over the past
      two decades, as the populations of patients at risk have continued to rise. Early
      and accurate diagnosis and the subsequent usage of appropriate antifungal therapy
      are difficult, which leads to a high mortality rate in patients with IFI. Along
      with the widespread use of antifungal prophylaxis, the epidemiology of invasive
      fungal pathogens has changed. Non-albicans Candida, Non-fumigatus Aspergillus,
      and molds other than Aspergillus have become more common pathogens causing
      invasive diseases, and most of these emerging fungi are resistant to or less
      susceptible than others to standard antifungal agents. Therefore, invasive
      infections due to these previously rare fungi are more difficult to treat.
      Advances in more potent and less toxic antifungal agents, such as second
      generation triazoles and echinocandins, may potentially improve the outcomes of
      these infections. Recent advances in detecting fungal cell-wall components and
      genomic DNA also allow earlier diagnosis. This article reviews the changing
      spectrum of invasive fungal infections and the introduction of recent advances in
      diagnostic tools and antifungal agents.

PMID- 18622669
TI  - Pathogen recognition by innate receptors.
AB  - Microbial infection elicits host immune responses through germline-encoded
      pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are
      evolutionarily conserved membrane-bound PRRs that recognize a broad spectrum of
      microbial components. Recent studies have clarified that two classes of cytosolic
      receptors, retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) and
      nucleotide binding oligomerization domain (NOD)-like receptors (NLRs), play
      important roles in the cytosolic recognition of invading pathogens. After
      microbial infection, the host utilizes these receptors differentially to mount
      robust immune responses. This review will describe pathogen recognition by these
      receptors, signaling pathways, and their in vivo roles in innate antiviral
      immunity.

PMID- 18622670
TI  - Antibiotic susceptibility of Haemophilus influenzae strains isolated from various
      clinical sources in Hokkaido Prefecture, Japan.
AB  - Any increase in beta-lactam-resistant Haemophilus influenzae is a serious problem
      in respiratory and otolaryngology medicine. In this study, we examined the
      antibiotic susceptibility and genotype of 457 clinical Haemophilus influenzae
      strains isolated in Hokkaido Prefecture, Japan. Strains with beta-lactam
      resistant mutations in gene encoding penicillin-binding protein 3 were more
      frequently found in lower respiratory tract specimens (sputa) than in upper
      respiratory tract specimens, such as rhinorrhea. The existence of the TEM-1 beta
      lactamase gene occurred more frequently in adult patients than in pediatric
      patients. The results suggest that beta-lactam-resistant or nonsusceptible
      strains are more prevalent in adult patients with respiratory diseases. We
      observed only a very few strains which were nonsuscpetible to third-generation
      cephalosporins (CEPs) and carbapenems. However, 12%-13% of the strains were shown
      to be resistant to penicillins and second-generation CEPs, and approximately 4%
      of the strains were shown to be nonsusceptible to fourth-generation CEPs. In
      addition, we identified tetracycline-resistant (2.8%), chloramphenicol-resistant
      (0.6%), clarithromycin-resistant (2.6%), and fluoroquinolone-nonsusceptible
      (approximately 2%) H. influenzae strains.

PMID- 18622671
TI  - Antimicrobial susceptibility and molecular epidemiological analysis of clinical
      strains of Pseudomonas aeruginosa.
AB  - Three hundred and seventy-one strains of Pseudomonas aeruginosa were isolated at
      the laboratory of Kyushu University Hospital in Japan from May 2002 through
      January 2003. Large proportions of isolated strains were resistant to
      carbapenems: 37.5% to imipenem, 21.3% to biapenem, and 18.3% to meropenem. A
      survey of injectable antibacterial agents used in our hospital during the
      corresponding period showed that carbapenems were most frequently used. Multidrug
      resistant P. aeruginosa (MDRP) strains and metallo-beta-lactamase producing
      strains were isolated at frequencies of 1.6% (6 strains) and 0.81% (3 strains),
      respectively. By molecular epidemiological analysis, neither MDRP nor metallo
      beta-lactamase producing strains were molecularly related, whereas some imipenem
      resistant strains appeared to be epidemic strains, suggesting a possibility that
      they might spread by nosocomial infection. To control nosocomial infection, it is
      important to know a trend in drug-resistant P. aeruginosa and to prevent the
      spread of not only MDRP and metallo-beta-lactamase producing strains but also
      imipenem-resistant P. aeruginosa strains.

PMID- 18622672
TI  - Clinical and microbiological characteristics of community-acquired pneumonia
      among human immunodeficiency virus-infected patients in northern Thailand.
AB  - Human immunodeficiency virus (HIV) infections are prevalent in Thailand. However,
      the clinical and microbiological characteristics of community-acquired pneumonia
      (CAP) in such patients are not completely clear at present. In the present study,
      we analyzed the characteristics of CAP in 191 HIV-infected patients (192
      episodes, 130 males and 61 females, mean age 32.9 years, range: 20-62) who had
      been admitted to Nakornping Hospital in northern Thailand between December 1996
      and January 2002. The mean peripheral blood CD4 lymphocyte count was 68.5/mm3
      (range: 0-791). The most common organisms detected in the blood of the subjects
      were as follows: Penicillium marneffei, 13, Salmonella spp., 5, Cryptococcus
      neoformans, 4, Staphylococcus aureus, 3, and Rhodococcus equi, 3, and the most
      common organisms detected in sputum included Haemophilus influenzae, 38, P.
      marneffei, 10, Streptococcus pneumoniae, 10, R. equi, 9, and S. aureus, 9. Life
      threatening meningitis in 5 (cryptococcal in 3 and tuberculous in 2),
      pneumothorax in 2, and tuberculous lymphadenitis in 1 were also noted, resulting
      in 21 fatalities (10.9%). The mean peripheral blood CD4 lymphocyte count for
      cases in which the subject died was 74.8/mm3 (range: 0-340). Logistic regression
      analysis demonstrated that high age (odds ratio of over 40 years: 15.62) and R.
      equi infection (odds ratio: 8.14) are related to death of HIV-infected patients
      with CAP. The above findings indicate that various types of organisms, including
      mixed organisms, cause CAP in HIV-infected patients in northern Thailand, and
      high age and R. equi infection seem to be risk factors for death.

PMID- 18622673
TI  - Peritoneal pharmacokinetics of cefepime in laparotomy patients with inflammatory
      bowel disease, and dosage considerations for surgical intra-abdominal infections
      based on pharmacodynamic assessment.
AB  - This study aimed to examine the peritoneal pharmacokinetics of cefepime and to
      assess its pharmacodynamic exposure in peritoneal fluid (PF). Cefepime (1 g) was
      administered to eight patients with inflammatory bowel disease before abdominal
      surgery. Venous blood and PF samples were obtained at the end of the 0.5-h
      infusion and at 1, 2, 3, 4, 5, and 6 h thereafter. Drug concentrations in plasma
      and PF were determined, analyzed pharmacokinetically, and used for a Monte Carlo
      simulation with minimum inhibitory concentration (MIC) data. Cefepime penetrated
      well into PF, with a maximum drug concentration in a PF/plasma ratio of 0.59 +/-
      0.15 (mean +/- SD, n = 8), and an area under the concentration-time curve ratio
      of 0.90 +/- 0.10. The probabilities of attaining the bacteriostatic and
      bactericidal targets (40% and 70% of the time above the MIC, respectively) in PF
      were > or =85% against Escherichia coli, Klebsiella species, and Enterobacter
      cloacae with 0.5 g every 12 h, 1 g every 12 h, 1 g every 8 h, and 2 g every 12 h.
      However, 1 g every 8 h or 2 g every 12 h was required for bacteriostatic and
      bactericidal probabilities > or =85% against Pseudomonas aeruginosa. These
      conventional regimens did not achieve a high probability against Bacteroides
      species. These results should help to give us a better understanding of the
      peritoneal pharmacokinetics of cefepime while also helping to choose the
      appropriate dosage to prevent surgical intra-abdominal infections on the basis of
      the pharmacodynamic assessment.

PMID- 18622674
TI  - An outbreak of Legionnaires' disease associated with a circulating bathwater
      system at a public bathhouse. I: a clinical analysis.
AB  - Few reports have analyzed the clinical manifestations of patients with
      Legionnaires' disease in large outbreaks throughout the world. We retrospectively
      evaluated the clinical presentation and prognostic factors in 76 patients with
      Legionnaires' disease, reported by local physicians, in a large outbreak
      resulting from contamination of the water in a public bathhouse in Miyazaki,
      Japan. Fever, gastrointestinal tract symptoms, and abnormal neurological findings
      were seen in 95%, 35%, and 21% of the 76 patients, respectively. Respiratory
      tract symptoms were seen in only 42% of the patients, although all of these
      patients revealed pneumonia on chest X-ray. Only 20 (31%) of the 64 patients who
      had microbiological tests were reported to have positive results for one of the
      three microbiological tests (sputum culture, serology, and urinary antigen) which
      are specific for Legionella infection. Based on univariate analysis, the
      existence of neurological symptoms, elevated levels of C-reactive protein and
      transaminases, hyponatremia, a positive urinary antigen test, and serological
      evidence of Legionella infection were independent risk factors for poor clinical
      courses in patients with Legionnaires' disease. Patients treated with
      antimicrobial agents, such as macrolides, tetracyclines, and/or fluoroquinolones,
      within 3 days of onset of illness exhibited significantly better outcomes, when
      assessed by a multivariate logistic-regression model, after adjusting for the
      severity of pneumonia. Taking a careful history and documenting potential
      Legionella exposure, as well as microbiological testing, is important for an
      accurate diagnosis of Legionnaires' disease. Antimicrobials effective against
      Legionella bacteria should be administered without delay in subjects with
      suspected Legionnaires' disease.

PMID- 18622675
TI  - An outbreak of Legionnaires' disease associated with a circulating bathwater
      system at a public bathhouse. II: radiological findings of pneumonia.
AB  - In July 2002, one of the largest outbreaks of Legionnaires' disease associated
      with a public bathhouse in Japan occurred in Miyazaki. The local government and
      the University of Miyazaki performed a retrospective investigation of those
      persons who were considered to have been exposed to Legionella. This
      investigation provided a unique opportunity to analyze the clinical presentation
      of patients with outbreak-associated Legionnaires' disease. The purpose of the
      present study was to analyze high-resolution computerized tomography (HRCT) scans
      for the characteristic findings of Legionnaires' disease and to evaluate the
      correlation between the radiological severity on the initial chest X-ray and the
      outcome of the patients. Radiological findings of HRCT were analyzed in 35
      patients. The radiological severity on chest X-ray was evaluated in 69 patients,
      utilizing the pneumonia scoring system proposed by the Research Committee on
      Legionnaires' Disease of the Ministry of Health, Labour and Welfare of the
      Japanese Government. Air-space consolidation, ground-glass opacity, and pleural
      effusion were common features on HRCT in patients with Legionnaires' disease.
      Typical HRCT findings showed bilateral multilobar infiltrates in the subpleural
      areas without centrilobular opacities. Multivariate logistic regression analysis
      identified male sex, short incubation period, high serum C-reactive protein, high
      serum alanine aminotransferase, hyponatremia, and positive Legionella urinary
      antigen test results as independent risk factors for high pneumonia scores.
      Patients with high pneumonia scores required significantly longer hospitalization
      and showed poor prognoses.

PMID- 18622676
TI  - Pharmacokinetic-pharmacodynamic target attainment analysis of cefozopran in
      Japanese adult patients.
AB  - This study aimed to perform a pharmacokinetic-pharmacodynamic (PK-PD) target
      attainment analysis to create a dosing strategy for cefozopran in Japanese adult
      patients. A total of 145 plasma concentration samples from 32 adult patients were
      used for a population pharmacokinetic modeling and Monte Carlo simulation to
      assess the probability of attaining the PK-PD target (70% of the time above the
      minimum inhibitory concentration for the bacterium). The final population
      pharmacokinetic model was based on a two-compartment model, and creatinine
      clearance (Cl(cr)) and body weight (BW) were the most significant covariates:
      Cl(l/h) = 0.0263 x Cl(cr) + 1.49, V (c)(l) = 0.185 x BW(0.931), Q(l/h) = 4.55, V
      (p)(l) = 5.86, where Cl is the clearance, V (c) is the volume of distribution of
      the central compartment, Q is the intercompartmental clearance, and V (p) is the
      volume of distribution of the peripheral compartment. The Monte Carlo simulation
      demonstrated that 1 g q 12 h achieved a PK-PD target attainment probability of >
      or =85% against Escherichia coli, Klebsiella pneumoniae, and Streptococcus
      pneumoniae isolates. However, against Haemophilus influenzae and Pseudomonas
      aeruginosa isolates, 1 g q 8 h and (2 g, 1 g, 1 g) q 8 h were required to achieve
      a high probability, which value varied with the Cl(cr) and BW of the patient.
      These results provide a PK-PD-based strategy for tailoring cefozopran regimens in
      Japanese adult patients.

PMID- 18622677
TI  - Gatifloxacin treatment for chronic prostatitis: a prospective multicenter
      clinical trial.
AB  - Antimicrobial treatment is usually used for chronic prostatitis. However, the
      efficacy of such treatment has not been fully evaluated. We conducted a study to
      evaluate the efficacy of gatifloxacin for patients with chronic prostatitis using
      the Japanese version of the National Institutes of Health Chronic Prostatitis
      Symptom Index (JPN-NIH CPSI). The study included 46 patients for final analysis.
      Patients who were younger than 65 years of age were treated with 200 mg
      gatifloxacin twice daily, and those who were 65 years and older were treated with
      100 mg gatifloxacin twice daily, for 4-8 weeks. The study consisted of 10
      patients in category II, 13 in category IIIA, 11 in category IIIB, and 12 who
      were unclassified. The gatifloxacin treatment resulted in significant reductions
      in the scores on the JPN-NIH CPSI. Of the total number of patients, 58.1% and
      27.9% were 25% and 50% responders, respectively, 4 weeks after treatment, and
      these figures improved to 66.7% and 33.3%, respectively, 8 weeks after treatment.
      No significant difference was found in the changes in symptom scores between
      Category II and Category IIIA/IIIB groups. In conclusion, gatifloxacin treatment
      improved the symptoms in patients with chronic bacterial and nonbacterial
      prostatitis. This study is the first in this country to evaluate the efficacy of
      antimicrobial treatment for chronic prostatitis by using the NIH CPSI.

PMID- 18622678
TI  - Development of breakpoints of cephems for intraabdominal infections based on
      pharmacokinetics and pharmacodynamics in the peritoneal fluid of patients.
AB  - We developed breakpoints for cephem antibacterial agents for intraabdominal
      infections based on pharmacokinetics (PK) and pharmacodynamics (PD) at the target
      site. Cefepime (CFPM), cefotiam (CTM), cefozopran (CZOP), and flomoxef (FMOX)
      were each administered to 8-10 patients before abdominal surgery, and venous
      blood and peritoneal fluid (PF) samples were obtained. The drug concentrations in
      plasma and PF were determined and analyzed using population pharmacokinetic
      modeling. Using the pharmacokinetic model parameters, a Monte Carlo simulation
      was conducted to estimate the probabilities of attaining the bacteriostatic and
      bactericidal targets (40% and 70% of the time above the minimum inhibitory
      concentration (T > MIC), respectively) in PF. The bacteriostatic and bactericidal
      breakpoints were determined as the highest MIC values at which the bacteriostatic
      and bactericidal probabilities in PF were > or =80%, which values varied with
      drug and dosing regimen. Site-specific PK-PD-based breakpoints for CFPM, CTM,
      CZOP, and FMOX are proposed, and should help us to select appropriate cephems and
      design their dosing regimens for intraabdominal infections.

PMID- 18622679
TI  - Effect of linezolid against postneurosurgical meningitis caused by methicillin
      resistant Staphylococcus epidermidis: case report.
AB  - A 67-year-old man who had twice previously undergone operations for a tuberculum
      sellae meningioma was admitted to hospital for further treatment. After the third
      surgical intervention, the patient developed persistent low-grade fever and
      impaired consciousness. Computed tomography, 1 week after surgery, showed
      postsurgical hydrocephalus. Cerebrospinal fluid (CSF) studies revealed high
      intracranial pressure (above 30 cm H2O), and increased cell count (1232/3). One
      week after the ventricular drainage, coagulase-negative Staphylococcus
      epidermidis was recovered from his CSF, and antimicrobial susceptibility results
      indicated that the organism was methicillin-resistant. After 14 days of
      intravenous vancomycin (VCM) administration failed, linezolid (LZD) was
      initialized intravenously, resulting in a resolution of the meningitis. After a
      ventriculoperitoneal shunt procedure was performed, LZD was continued orally,
      which resulted in a cure. CSF penetration by VCM is reported to be poor, i.e.,
      approximately 10% of serum concentration, which may explain its lack of efficacy.
      In this case, the penetration of LZD into the CSF was 58.9% of the peak value and
      133% of the trough value of serum concentrations. LZD must be considered one of
      the first-line treatments against surgical-site infection in neurosurgery caused
      by methicillin-resistant Staphylococci.

PMID- 18622680
TI  - HIV-2 amino acid substitutions in Gag and Env proteins occurring simultaneously
      with viral load upsurge in a drug-naive patient.
AB  - It has been reported that the peptides of human immunodeficiency virus type 2
      (HIV-2) most frequently recognized by cytotoxic T lymphocytes are firstly in Gag
      and secondly in Env proteins. In the present case study, we attempted to observe
      amino acid substitutions in Gag and Env proteins and related parameters possibly
      associated with an increase in HIV-2 load. A sudden, eightfold, increase in HIV-2
      load occurred in a drug-naive patient with human leukocyte antigen-B*5801 during
      the last phase of a longitudinal observation period from months 29 to 40. The
      genetic diversity of Gag and Env increased gradually prior to the HIV-2 load
      increase. The proportions of synonymous substitutions in both Gag and Env were
      greater than the proportions of nonsynonymous substitutions at every sampling
      point for 40 months, and the net charge of the V3-loop increased from months 29
      to 40. Three amino acid substitutions (V2861 in Gag, K303T and N337 K/R in Env)
      were observed from months 29 to 40. Only one amino acid substitution (V286I) was
      observed with an increase in HIV-2 load in the Gag region where the clustering of
      epitopes was reported. These results suggest that the sites encompassing these
      three substituted positions are candidates for HIV-2 epitopes, although further
      careful examinations will be required.

PMID- 18622681
TI  - Pharmacokinetics of repeated dosing of linezolid in a hemodialysis patient with
      chronic renal failure.
AB  - Linezolid (LZD) is thought not to require dose adjustment in patients with renal
      dysfunction, making it a drug of choice for these patients. However, in the
      current study we show LZD accumulation occurring with repeated dosing during
      hemodialysis in a 64-year-old man receiving hemodialysis treatment. In this
      patient, methicillin-resistant Staphylococcus aureus (MRSA) caused an abscess
      under the abdominal wall due to wound infection after colon cancer surgery.
      Treatment was initiated with intravenous LZD (600 mg) every 12 h. However,
      pancytopenia and liver dysfunction occurred during the LZD administration period.
      A high trough level, of 15-20 microg/ml, during LZD administration was determined
      from stored blood biochemistry samples, and pharmacokinetic parameters, estimated
      by the Bayesian nonlinear least squares method, were as follows: clearance (CL),
      1.56 l/h; clearance during hemodialysis (CL(HD)), 2.23 l/h; volume of
      distribution (Vd), 18.69 l; and area under the curve (AUC), 384.07 microg/ml . h.
      Simulation of the serum concentration-time profile from the estimated
      pharmacokinetic parameters gave a trough level about four to five times higher
      than that in healthy individuals in the early administration period, indicating
      LZD accumulation in blood. These findings suggest a causal relationship between
      the high LZD level and the adverse effects. The cause of the high LZD level is
      unclear, but the findings indicate that careful monitoring and dose adjustment of
      LZD is necessary in hemodialysis patients.

PMID- 18622682
TI  - Legionella pneumonia caused by Legionella pneumophila serogroup 2: second case
      report in Japan.
AB  - A 56-year-old man with a 3-day history of a chilly sensation and general fatigue
      presented to a hospital in his neighborhood. He was diagnosed as having pneumonia
      and immediately treated with intravenous ceftriaxone sodium, but his respiratory
      condition deteriorated and he developed symptoms of restlessness. Although
      Legionella urinary antigen detection tests were negative, his clinical course
      suggested Legionella pneumonia. After his treatment was changed to intravenous
      ciprofloxacin and oral clarithromycin, his general condition gradually improved.
      Later, Legionella pneumophila serogroup 2 was isolated from a bronchoalveolar
      lavage specimen. This was considered to be the causative organism. In our
      literature search, this was only the second case of Legionella pneumonia caused
      by Legionella pneumophila serogroup 2 in Japan.

PMID- 18622683
TI  - Utilization of Bombyx mori larvae as a surrogate animal model for evaluation of
      the anti-infective potential of oxazolidinones.
AB  - Silkworm (Bombyx mori) larvae were investigated as an alternative animal model
      for the efficacy testing of novel oxazolidinones. The minimal lethal dose (MLD)
      for Staphylococcus aureus was 1-5 x 10(7) CFU per larva, exhibiting more than 90%
      mortality within 2 to 4 days post-infection. Treatment with vancomycin,
      linezolid, and novel oxazolidinones (RBx 7644, RBx 8700, and RBx 2006171) showed
      survival in a dose-dependent manner. The antibacterial potential of RBx 7644 and
      RBx 8700 was compared with that of linezolid and that of vancomycin and the
      effective doses (ED)50 obtained in the silkworm model were 37.89, 24.96, 13.38,
      and 30.72 mg/kg body weight, respectively. The ED50 values showed a similar trend
      in a murine model of infection. Owing to the small size of the larvae, very small
      amounts of new chemical entities (NCEs) are required to test their in vivo
      efficacy in this model. Thus, the silkworm model may be used in the early stage
      of new discovery research.

PMID- 18622684
TI  - Penetration into and exposure of cefozopran in pelvic retroperitoneal space
      exudate.
AB  - This study aimed to examine the penetration into and exposure of cefozopran in
      the pelvic retroperitoneal space exudate of patients undergoing radical
      hysterectomy and pelvic lymphadenectomy. Cefozopran (1 g) was administered by 1-h
      infusion after the end of surgery, and venous blood and exudate samples were
      obtained 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 8 h thereafter. Drug concentrations in
      serum and the exudate were determined by a bioassay, analyzed
      pharmacokinetically, and used for a Monte Carlo simulation with minimum
      inhibitory concentration (MIC) data. The exudate/serum ratio of the area under
      the drug concentration-time curve was 0.76 +/- 0.19 (mean +/- SD), and the
      simulated concentrations were higher in the exudate than in serum after 2.4 h
      post-dose. The probability of attaining the pharmacodynamic exposure target (70%
      of the time above the MIC; i.e., probability of target attainment; PTA) was 94.9%
      and 100%, respectively, against Escherichia coli and Klebsiella species with 1 g
      every 12 h; however, 1 g every 8 h was required for a PTA value of 90% or more at
      an MIC of 8 microg/ml. We consider that these results will help clinicians to
      better understand the penetration into and exposure of cefozopran in the female
      genital cavity, while also helping to rationalize the dosage of this agent for
      gynecological-surgery infections.

PMID- 18622685
TI  - Guidelines for implementation of clinical studies on surgical antimicrobial
      prophylaxis (2007).

PMID- 18622686
TI  - Light sources for photodynamic inactivation of bacteria.
AB  - Bacteria have an important role in human and animal morbidity, and a great number
      of them have developed antibiotic resistance. In the past recent years a new way
      of dealing with this problem has been studied: photodynamic inactivation. This
      method is based on administration of a photosensitizing substance that fixes
      itself in the bacterial cell followed by exposure to a light source. In the
      experiments done by many researchers on photodynamic inactivation of bacteria,
      both coherent and non-coherent light sources were used. This article is a review
      of these light sources and of some experimental results obtained by different
      authors.

PMID- 18622687
TI  - Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine
      production by the selective PPARbeta/delta ligand GW0742.
AB  - OBJECTIVE: To define the anti-inflammatory effects of PPARbeta/delta activation
      by use of the selective PPARbeta/delta ligand (GW0742) in a model of
      lipopolysaccharide (LPS)-induced pulmonary inflammation. METHODS: Male BALB/c
      mice were pretreated for three days with the PPARbeta/delta agonist, GW0742,
      prior to induction of LPS-mediated pulmonary inflammation. Bronchial alveolar
      lavage fluid (BALF) was analyzed for inflammatory cell influx and for levels of
      pro-inflammatory mediators. BALF-derived inflammatory cells were also collected
      for mRNA analysis. RESULTS: Pretreatment with GW0742 resulted in a significant
      decrease in leukocyte recruitment into the pulmonary space. Protein and mRNA
      levels of the pro-inflammatory cytokines IL-6, IL-1beta and TNFalpha in BALF were
      found to be significantly decreased in GW0742-treated animals (30 mg/kg). A
      significant decrease in granulocyte macrophage-colony stimulating factor (GM
      CSF), a major regulator of neutrophil chemotaxis (via its downstream actions on
      TNFalpha and other cytokines/chemokines), activation and survival, was also noted
      in the BALF levels of GW0742-treated animals. CONCLUSIONS: The present study
      demonstrates that activation of PPARbeta/delta attenuates the degree of
      inflammation in a model of LPS-induced pulmonary inflammation and may therefore
      represent a novel therapeutic approach for the treatment of inflammation-mediated
      pathologies.

PMID- 18622688
TI  - Endoplasmic reticulum stress contributes to the cell death induced by UCH-L1
      inhibitor.
AB  - At the neuropathological level, Parkinson's disease (PD) is characterized by the
      accumulation of misfolded proteins, which can trigger the unfolded protein
      response (UPR). UCH-L1 is a component of ubiquitin proteasome system (UPS). It is
      reported that the loss of its function will impair ubiquitin proteasome system
      and cause toxicity to cells. But its mechanism has not been illustrated. In this
      study, we detected the protein expression of Bip/Grp78 and the spliced form of
      XBP-1 to examine the activation of unfolded protein response after SK-N-SH cells
      being treated with LDN-57444, a UCH-L1 inhibitor which could inhibit UCH-L1
      hydrolase activity. Our data showed that UCH-L1 inhibitor was able to cause cell
      death through the apoptosis pathway by decreasing the activity of ubiquitin
      proteasome system and increasing the levels of highly ubiquitinated proteins,
      both of which can activate unfolded protein response. There is a lot of evidence
      that unfolded protein response is activated as a protective response at the early
      stage of the stress; this protective response can switch to a pro-apoptotic
      response when the stress persists. In this study, we demonstrated this switch by
      detecting the upregulation of CHOP/Gadd153. Taken together, our data indicated
      that the apoptosis induced by UCH-L1 inhibitor may be triggered by the activation
      of endoplasmic reticulum stress (ERS). Moreover, we provide a new cell model for
      studying the roles of UCH-L1 in Parkinson's disease.

PMID- 18622689
TI  - Expression of the ZEB1 (deltaEF1) transcription factor in human: additional
      insights.
AB  - The zinc finger E-box binding transcription factor ZEB1 (deltaEF1/Nil-2
      a/AREB6/zfhx1a/TCF8/zfhep/BZP) is emerging as an important regulator of the
      epithelial to mesenchymal transitions (EMT) required for development and cancer
      metastasis. ZEB1 promotes EMT by repressing genes contributing to the epithelial
      phenotype while activating those associated with the mesenchymal phenotype. TCF8
      (zfhx1a), the gene encoding ZEB1, is induced by several potentially oncogenic
      ligands including TGF-beta, estrogen, and progesterone. TGF-beta appears to
      activate EMT, at least in part, by inducing ZEB1. However, our understanding of
      how ZEB1 contributes to signaling pathways elicited by estrogen and progesterone
      is quite limited, as is our understanding of its functional roles in normal adult
      tissues. To begin to address these questions, a human tissue mRNA array analysis
      was done. In adults, the highest ZEB1 mRNA expression is in bladder and uterus,
      whereas in the fetus highest expression is in lung, thymus, and heart. To further
      investigate the regulation of TCF8 by estrogen, ZEB1 mRNA was measured in ten
      estrogen-responsive cell lines, but it is only induced in the OV266 ovarian
      carcinoma line. Although high expression of ZEB1 mRNA is estrogen-dependent in
      normal human ovarian and endometrial biopsies, high expression is estrogen
      independent in late stage ovarian and endometrial carcinomas, raising the
      possibility that deregulated expression promotes cancer progression. In contrast,
      TCF8 is at least partially deleted in 4 of 5 well-differentiated, grade I
      endometrial carcinomas, which may contribute to their non-aggressive phenotype.
      These data support the contention that high ZEB1 encourages gynecologic carcinoma
      progression.

PMID- 18622690
TI  - CK2alpha/CK1alpha chimeras are sensitive to regulation by the CK2beta subunit.
AB  - The effect of CK2beta on the activity of CK2alpha and other protein kinases that
      can bind this regulatory subunit is not fully understood. In an attempt to
      improve our understanding of this effect, chimeras of CK2alpha and CK1alpha have
      been constructed. These chimeras contain different portions of the CK2alpha amino
      terminal region that are involved in the interaction with CK2beta to form CK2
      tetramers. In the case of chimeras 1 and 2, the portions of CK2alpha replace the
      corresponding segments of CK1alpha. In the case of chimera 3, the fragment of
      CK2alpha is added to the whole CK1alpha molecule with the exception of the
      initial methionine. Chimera 3 has 8% of the activity of CK1alphaWT, while
      chimeras 1 and 2 are 3 orders of magnitude less active than CK1alphaWT. All three
      chimeras bind tightly to CK2beta, but only chimeras 1 and 2 are significantly
      stimulated in their capacity to phosphorylate casein and canonical peptide
      substrates by addition of the regulatory subunit. No stimulation was observed
      with phosvitin or non-canonical peptides derived from beta-catenin. CK2beta
      protects chimeras 1 and 2 from thermal inactivation. Chimera 2 can phosphorylate
      CK2beta and autophosphorylate; however, salt concentrations above 150 mM NaCl
      eliminate the phosphorylation of CK2beta but not the autophosphorylation of
      chimera 2. Similarly, high salt decrease the stimulatory effect of CK2beta on the
      phosphorylation of casein.

PMID- 18622691
TI  - In vitro effects on MCF-7 breast cancer cells of signal transduction
      inhibitor/tamoxifen/eicosapentaenoic acid combinations and their simultaneous
      delivery across skin.
AB  - PURPOSE: To determine the in vitro effects of simultaneously administered
      LY29400, PD98059, tamoxifen and eicosapentaenoic acid (EPA) on breast cancer
      cells, and determine their transcutaneous delivery. METHODS: Growth assays were
      performed on MCF-7 cells challenged with IC(50) and permeated concentrations of
      PD98059, LY294002 and tamoxifen firstly in isolation then combined. Permeation
      studies were performed using PD98059 and LY294002 (singly or simultaneously) in
      DMSO then fish oil, with enhancers. Immunocytochemical detection of phospho-MAPK,
      phospho-Akt, total COX-2 and Ki-67 was performed. RESULTS: When applied singly,
      fluxes of PD98059 and LY294002 were 0.09 +/- 0.008 and 0.14 +/- 0.045 microg cm(
      2) h(-1), respectively; applied simultaneously, 0.18 +/- 0.045 and 0.49 +/- 0.051
      microg cm(-2) h(-1). Permeated concentrations of PD98059 and LY294002 reduced
      growth to 13.78 +/- 0.63%. Fish oil plus 2.5% DMSO/ethanol allowed 5.96 +/- 0.9
      and 7.7 +/- 1.2 microg cm(-2) of PD98059 and LY294002 to permeate after 48 h.
      CONCLUSIONS: PD98059 and LY294002 permeate excised skin at therapeutically useful
      rates, and also demonstrate growth inhibitory effects on MCF-7 cancer cells.
      Synergism was noted in co-transport across skin and activity against cancer
      cells. A formulation based on fish oil is potentially skin friendly; simultaneous
      permeation of EPA provides further anti-cancer action.

PMID- 18622692
TI  - Acidic microclimate pH distribution in PLGA microspheres monitored by confocal
      laser scanning microscopy.
AB  - PURPOSE: The acidic microclimate pH (micropH) distribution inside poly(lactic-co
      glycolic acid) (PLGA) microspheres was monitored quantitatively as a function of
      several formulation variables. METHODS: A ratiometric method by confocal laser
      scanning microscopy with Lysosensor yellow/blue dextran was adapted from those
      previously reported, and micropH distribution kinetics inside microspheres was
      examined during incubation under physiologic conditions for 4 weeks. Effects of
      PLGA molecular weight (MW) and lactic/glycolic acid ratio, microspheres size and
      preparation method, and polymer blending with poly(ethylene glycol) (PEG) were
      evaluated. RESULTS: micropH kinetics was accurately sensed over a broadly acidic
      range (2.8 < micropH < 5.8) and was more acidic and variable inside PLGA with
      lower MW and lactic/glycolic acid ratio. Lower micropH was found in larger
      microspheres of lower MW polymers, but size effects for lactic-rich polymers were
      insignificant during 4 weeks. Microspheres prepared by the oil-in-oil emulsion
      method were less acidic than those prepared by double emulsion, and blending PLGA
      50/50 with 20% PEG increased micropH significantly (micropH > 5 throughout
      incubation). CONCLUSIONS: Coupling this method with that previously developed
      (SNARF-1 dextran for micropH 5.8-8.0) should provide microclimate pH mapping over
      the entire useful pH range (2.8-8.0) for optimization of PLGA delivery of pH
      sensitive bioactive substances.

PMID- 18622693
TI  - Genetic strategies for dissecting mammalian and Drosophila voltage-dependent
      anion channel functions.
AB  - Voltage-dependent anion channels (VDACs), also known as mitochondrial porins, are
      a family of small pore-forming proteins of the mitochondrial outer membrane that
      are found in all eukaryotes. VDACs are thought to play important roles in the
      regulated flux of metabolites between the cytosolic and mitochondrial
      compartments, in overall energy metabolism via interactions with cytosolic
      kinases, and a debated role in programmed cell death (apoptosis). The mammalian
      genome contains three VDAC loci termed Vdac1, Vdac2, and Vdac3, raising the
      question as to what function each isoform may be performing. Based upon
      expression studies of the mouse VDACs in yeast, biophysical differences can be
      identified but the physiologic significance of these differences remains unclear.
      Creation of "knockout" cell lines and mice that lack one or more VDAC isoforms
      has led to the characterization of distinct phenotypes that provide a different
      set of insights into function which must be interpreted in the context of complex
      physiologic systems. Functions in male reproduction, the central nervous system
      and glucose homeostasis have been identified and require a deeper and more
      mechanistic examination. Annotation of the genome sequence of Drosophila
      melanogaster has recently revealed three additional genes (CG17137, CG17139,
      CG17140) with homology to porin, the previously described gene that encodes the
      VDAC of D. melanogaster. Molecular analysis of these novel VDACs has revealed a
      complex pattern of gene organization and expression. Sequence comparisons with
      other insect VDAC homologs suggest that this gene family evolved through a
      mechanism of duplication and divergence from an ancestral VDAC gene during the
      radiation of the genus Drosophila. Striking similarities to mouse VDAC mutants
      can be found that emphasize the conservation of function over a long evolutionary
      time frame.

PMID- 18622694
TI  - Examining externalizing behavior trajectories of youth in group homes: is there
      evidence for peer contagion?
AB  - Although concerns about peer contagion are often cited in critiques of group
      treatments for troubled youths, few studies have examined the effects of exposure
      to deviant peers in residential group care settings. This study used
      administrative data of youth served at Boys Town, a nationally-known group care
      provider. Using latent class growth analysis, this study identified the
      externalizing behavior trajectories of youth in group care as well as the
      behavior trajectory of the peers with whom they lived, assessed the relationship
      between youth trajectory classes and individual and peer group characteristics as
      well as the relationship between an individual youth's behavior pattern and the
      behavior pattern of proximal peers. Several results suggested the presence of
      peer contagion in group care: a trajectory class of gradually increasing
      externalizing behavior problems, the strength of deviant peer density in
      predicting an individual youth's externalizing behavior trajectories and
      significant associations between behavior patterns of youth and proximal peers.
      While there is some evidence that suggests an increase in problem behavior during
      care, results from this study indicated that over 90% of the youth did not have
      an increase in problem behaviors and that positive peer influences may also be
      protective and inhibit problem behaviors.

PMID- 18622695
TI  - Three-dimensional pathological size assessment in primary breast carcinoma.
AB  - Maximal tumor diameter (MD) is traditionally an important prognostic factor in
      breast cancer. It must be questioned, however, how well a one-dimensional
      parameter alone can represent the actual morphologic condition of a three
      dimensional body. Along with the pathologically assessed MD and two perpendicular
      diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional
      parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast
      carcinomas of limited size (10-40 mm) were calculated. The dependent prognostic
      variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were
      highly significant predictors of ALNI; these variables had similar levels of
      prediction accuracy (univariate analyses: MD: P = 0.0003, TV: P = 0.0009, TSA: P
      < 0.0001; multivariate analyses: MD: P = 0.0018, TV: P = 0.0109, TSA: P = 0.0009;
      pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain
      variations in tumor shape, TV and TSA with similar MD, there is no evidence that
      three-dimensional pathologic measurements (TV/TSA) are more precise prognostic
      predictors of ALNI compared to the one-dimensional measurement alone.

PMID- 18622696
TI  - Establishment of an in vitro estrogen-dependent mouse mammary tumor model: a new
      tool to understand estrogen responsiveness and development of tamoxifen
      resistance in the context of stromal-epithelial interactions.
AB  - Currently, to our knowledge, there are no continuous cell lines derived from
      estrogen dependent, tamoxifen sensitive spontaneous mouse mammary carcinomas. We
      describe here the establishment and characterization of a cell line derived from
      the M05 mouse mammary tumor, LM05-Mix, composed of both an epithelial and a
      fibroblastic component. From it the respective epithelial LM05-E and fibroblastic
      LM05-F cell lines were generated by limiting dilution. Immunofluorescence studies
      confirmed that the epithelial cells were positive for E-cadherin, cytokeratins
      and vimentin whereas the fibroblastic cells were negative for the epithelial
      markers and positive for alpha-smooth muscle actin and vimentin. Both cell types
      expressed estrogen and progesterone receptors, although only the epithelial LM05
      E cells were stimulated by estradiol and inhibited by tamoxifen. In the
      bicellular LM05-Mix cell line estradiol proved to stimulate cell proliferation
      whereas the response to tamoxifen was dependent on confluency and the degree of
      epithelial-fibroblastic interactions. The presence of membrane estrogen receptors
      in both cell types was suggested by the achievement of non-genomic responses to
      short treatments with estradiol, leading to the phosphorylation of ERK1/2.
      Finally, cytogenetic studies suggest that these two cell types represent
      independent cell populations within the tumor and would not be the result of an
      epithelial-mesenchymal transition. This model presents itself as a valuable
      alternative for the study of estrogen responsiveness and tamoxifen resistance in
      the context of epithelial-stromal interactions.

PMID- 18622697
TI  - Population estimates of survival in women with screen-detected and symptomatic
      breast cancer taking account of lead time and length bias.
AB  - BACKGROUND: Evidence of the impact of breast screening is limited by biases
      inherent in non-randomised studies and often by lack of complete population data.
      We address this by estimating the effect of screen detection on cause-specific
      fatality in breast cancer, corrected for all potential biases, using population
      cancer registry data. METHODS: Subjects (N = 26,766) comprised all breast cancers
      notified to the West Midlands Cancer Intelligence Unit and diagnosed in women
      aged 50-74, from 1988 to 2004. These included 10,100 screen-detected and 15,862
      symptomatic breast cancers (6,009 women with interval cancers and 9,853 who had
      not attended screening). Our endpoint was survival to death from breast cancer.
      We estimated the relative risk (RR) of 10-year cause-specific fatality (screen
      detected compared to symptomatic cancers) correcting for lead time bias and
      performing sensitivity analyses for length bias. To exclude self-selection bias,
      survival analyses were also performed with interval cancers as the comparator
      symptomatic women. FINDINGS: Uncorrected RR associated with screen-detection was
      0.34 (95% CI 0.31-0.37). Correcting for lead time, RR was 0.49 (95% CI 0.45
      0.53); length bias analyses gave a range of RR corrected for both phenomena of
      0.49-0.59, with a median of 0.51. Self-selection bias-corrected estimates yielded
      a median RR of 0.68. INTERPRETATION: After adjusting for various potential
      biases, women with screen-detected breast cancer have a substantial survival
      advantage over those with symptomatic breast cancer.

PMID- 18622698
TI  - Aquatic risk assessment of copper in freshwater and saltwater ecosystems of South
      Florida.
AB  - A screening-level aquatic risk assessment was conducted for copper in south
      Florida's freshwater and saltwater environments. Risk was quantified by comparing
      the overlap between the probability distributions of copper exposure from surface
      water and sediment with the probability distributions of effects data obtained
      from laboratory studies. Copper concentrations in surface water and sediment in
      south Florida were summarized by county. For surface water, the highest
      concentrations of copper were found in Martin and St. Lucie counties for
      freshwater and saltwater, respectively. From the exposure probability
      distributions, the 90th centile values were estimated at 14.0 microg/L and 15.4
      microg/L in freshwater and saltwater, respectively. Copper concentrations in
      sediment were evaluated from a probability distribution of predicted pore water
      concentrations. The 90th centile values of pore water concentrations from
      freshwater sediments ranged from 5.0 microg/L in Palm Beach County to 71.7
      microg/L in Broward County. In saltwater sediments, the 90th centile values for
      pore water ranged from 26.1 microg/L in St. Lucie County to 27.3 microg/L in
      Miami-Dade County. Ecological effects data were obtained for acute and chronic
      copper effects in freshwater and saltwater. The 10th centile values for acute
      effects data were 21.2 microg/L and 9.8 microg/L for freshwater and saltwater
      species, respectively. For chronic effects, the 10th centile values were 3.8
      microg/L and 3.9 microg/L for freshwater and saltwater species, respectively. The
      risk of acute copper exposure in surface water was generally low; however, the
      potential for ecological risk from chronic copper exposure was low to high in
      several counties including Lee, Martin, and St. Lucie counties. The risk of acute
      copper exposure in porewater from freshwater sediments also was low with the
      exception of St. Lucie and Broward counties. However, porewater from saltwater
      sediments posed a significant acute risk in Miami-Dade and St. Lucie counties. In
      porewater from freshwater and saltwater sediments chronic risk was high in
      counties with sufficient data available to calculate risk estimates.

PMID- 18622699
TI  - Metal concentrations in osprey (Pandion haliaetus) populations in the Florida Bay
      estuary.
AB  - Mercury and trace metal contamination is a concern in the Florida Bay estuary,
      but the effects on biological pathways are not very well understood. The analysis
      of mercury and trace metals (beryllium, vanadium, chromium, cobalt, nickel,
      copper, arsenic, cadmium, antimony, and lead) was conducted on tissues of adult
      and juvenile osprey (Pandion haliaetus) to examine the bioaccumulation and
      distribution in Florida Bay. Mercury concentrations were found at levels
      associated with decreased reproductive success, and no significant differences
      were found between adult and juvenile samples. Concentrations of other trace
      metals were generally below levels known to cause environmental problems. Mercury
      levels were particularly high in birds from central and eastern Florida Bay. In
      addition to mercury, vanadium was the only trace metal that showed significant
      geographic variation. Mercury concentrations in adult samples were comparable to
      levels reported in adult osprey from two other sites in North America, but
      concentrations in juvenile tissues were higher in Florida Bay. Although ospreys
      are a potential biomonitoring species for mercury contamination, further inter
      population comparisons are needed, as well as additional information about the
      risks associated with bioaccumulation.

PMID- 18622700
TI  - The analysis of multivariate recurrent events with partially missing event types.
AB  - In many clinical studies, subjects are at risk of experiencing more than one type
      of potentially recurrent event. In some situations, however, the occurrence of an
      event is observed, but the specific type is not determined. We consider the
      analysis of this type of incomplete data when the objectives are to summarize
      features of conditional intensity functions and associated treatment effects, and
      to study the association between different types of event. Here we describe a
      likelihood approach based on joint models for the multi-type recurrent events
      where parameter estimation is obtained from a Monte-Carlo EM algorithm.
      Simulation studies show that the proposed method gives unbiased estimators for
      regression coefficients and variance-covariance parameters, and the coverage
      probabilities of confidence intervals for regression coefficients are close to
      the nominal level. When the distribution of the frailty variable is misspecified,
      the method still provides estimators of the regression coefficients with good
      properties. The proposed method is applied to a motivating data set from an
      asthma study in which exacerbations were to be sub-typed by cellular analysis of
      sputum samples as eosinophilic or non-eosinophilic.

PMID- 18622701
TI  - Candida albicans infection delays duodenal ulcer healing in cysteamine-induced
      duodenal ulcers in rats.
AB  - A low curability of ulcers infected with Candida has been reported in the
      literature. The aim of the study reported here was to investigate experimentally
      whether Candida infection affects the healing of ulcers. Candida albicans (the
      Candida group) or saline (the control group) was administered intragastrically
      into rats with a cysteamine-induced duodenal ulcer. The duodenal lesions,
      vascular endothelial growth factor A (VEGF-A) and proliferating cell nuclear
      antigen (PCNA) were assessed. On Day 7 post-administration, 70.4% rats of the
      Candida group had a duodenal ulcer compared with 33.3% in the control group (P <
      0.05). The duodenal ulcer in the Candida group was significantly larger and
      deeper than that in the control group. The number of VEGF-A- and PCNA-positive
      cells was smaller and the area of VEGF-A expression was lower in the Candida
      group. Using a rat model, we have demonstrated that Candida infection can delay
      the wound healing process of duodenal ulcers by means of a low expression of VEGF
      A and PCNA.

PMID- 18622702
TI  - Validation of a finite element model of the young normal lower cervical spine.
AB  - A Finite Element Model (FEM) of the young adult human cervical spine has been
      developed as a first step in studying the process of spondylotic degeneration.
      The model was developed using normal geometry and material properties for the
      lower cervical spine. The model used a three-zone composite disc annulus to
      reflect the different material properties of the anterior, posterior, and lateral
      regions of the annulus. Nonlinear ligaments were implemented with a toe region to
      help the model achieve greater flexibility at low loads. The model was validated
      against experimental data for normal, nondegenerated cervical spines tested in
      flexion and extension, right and left lateral bending, and right and left axial
      rotation at loads of 0.33, 0.5, 1.0, 1.5, and 2.0 Nm. The model was within in
      vitro experimental standard deviation corridors 100% of the load range for right
      and left lateral bending. The model was within 80% of the load response corridors
      for extension and flexion with a deviation <0.3 degrees from the SD corridors.
      For axial rotation, the model was within 70% of the SD corridors for left axial
      rotation within 83% of right axial rotation responses. The deviation from SD
      corridors for axial rotation was generally <0.2 degrees.

PMID- 18622703
TI  - The effects of long-term spinal cord injury on mechanical properties of the rat
      urinary bladder.
AB  - We have demonstrated that bladder wall tissue in spinal cord injury (SCI) rats at
      10 days post-injury is more compliant and accompanied by changes in material
      class from orthotropic to isotropic as compared to normal tissue. The present
      study examined the long-term effects (3-, 6-, and 10-weeks) post-SCI on the
      mechanical properties of bladder wall tissues, along with quantitative changes in
      smooth muscle orientation and collagen and elastin content. Bladder wall
      compliance (defined as det(F) - 1 under an equi-biaxial stress state of 100 kPa,
      where F is the deformation gradient tensor) was found to be significantly greater
      at 3- and 6-weeks (0.873 +/- 0.092 and 0.864 +/- 0.112, respectively) when
      compared to the normal bladders (0.260 +/- 0.028), but at 10 weeks the compliance
      reduced (0.389 +/- 0.061) to near that of normal bladders. This trend in
      mechanical compliance closely paralleled the collagen/elastin ratio. Moreover,
      changes in material class, assessed using a graphical technique, correlated
      closely with quantitative changes in smooth muscle fiber orientation. The results
      of the present study provide the first evidence that, while similarities exist
      between acute and chronic responses of the urinary bladder wall tissue to SCI,
      the overall alterations are distinct, result in profound and complex time
      dependent changes in bladder wall structure, and will lay the basis for
      simulations of the bladder wall disease process.

PMID- 18622704
TI  - HIV-1 viral genes and mitochondrial apoptosis.
AB  - The mitochondrion is an organelle that regulates various cellular functions
      including the production of energy and programmed cell death. Aberrant
      mitochondrial function is often concomitant with various cytopathies and medical
      disorders. The mitochondrial membrane plays a key role in the induction of
      cellular apoptosis, and its destabilization, as triggered by both intracellular
      and extracellular stimuli, results in the release of proapoptotic factors into
      the cytosol. Not surprisingly, proteins from the human immunodeficiency virus
      type 1 (HIV) have been implicated in exploiting this organelle to promote the
      targeted depletion of key immune cells, which assists in viral evasion of the
      immune system and contributes to the characteristic global immunodeficiency
      observed during progression of disease. Here we review the mechanisms by which
      HIV affects the mitochondrion, and suggest that various viral-associated genes
      may directly regulate apoptotic cell death.

PMID- 18622705
TI  - Rare sugar D-allose induces programmed cell death in hormone refractory prostate
      cancer cells.
AB  - Development of effective agents for treatment of hormone-refractory prostate
      cancer (HRPC) has become a national medical priority. D-Allose is a
      monosaccharide (C-3 epimer of glucose) distributed rarely in nature; because of
      its scarcity and cost, the biological effect has hardly been studied. In the
      present study, we demonstrated the inhibitory action of D-allose on proliferation
      of human HRPC cell lines, DU145 and PC-3 in a dose- and time-dependent manner,
      while human normal prostate epithelial (NPE) cell line, PrEC showed no remarkable
      effect. In vitro treatment of D-allose resulted in the alteration of Bcl-2/Bax
      ratio in favor of apoptosis (programmed cell death, PCD) in both the HRPC cell
      lines, which was associated with the lowering of mitochondrial transmembrane
      potential (Deltapsi(m)) and the release of cytochrome C (cyt C), the cleavage of
      caspase 3 and poly (ADP-ribose) polymerase (PARP), and the elevation of calcium
      concentration in cytosol ([Ca(2+)](c)). D-Allose also induced G1 phase arrest of
      the cell cycle in DU145 cell line. This study for the first time suggested the
      antiproliferative effect of D-allose through induction of PCD in HRPC cell lines,
      which could be due to the modulation of mitochondria mediated intrinsic apoptotic
      pathway.

PMID- 18622707
TI  - Prevalence of infection with hepatitis B and C viruses and co-infection with HIV
      in three jails: a case for viral hepatitis prevention in jails in the United
      States.
AB  - Hepatitis B vaccination and targeted testing for hepatitis C virus (HCV) are
      recommended for jails with medical services available. This study estimates
      hepatitis B virus (HBV) and HCV infection prevalence among jail inmates, since
      most previous studies have been conducted among prison inmates. Prison and jail
      populations differ: jails hold a wide spectrum of persons for an average of 10-20
      days, including persons awaiting arraignment, trial, conviction, or sentencing,
      while prisons typically hold convicted criminals for at least 1 year. A
      stratified random sample of sera obtained during routine syphilis testing of
      inmates entering jails in Chicago (March-April 2000), Detroit (March-August
      1999), and San Francisco (June 1999-December 2000) was tested for serologic
      markers of HBV and HCV infection. All sera had been previously tested for
      antibody to HIV (anti-HIV). A total of 1,292 serum samples (12% of new inmates)
      was tested. Antibody to HCV (anti-HCV) prevalence was 13%. Antibody to hepatitis
      B core antigen (anti-HBc) prevalence was 19%, and hepatitis B surface antigen
      (HBsAg) prevalence was 0.9%; 12% had serologic evidence of hepatitis B
      vaccination. Hispanics had high rates of chronic HBV infection (3.6% HBsAg
      positive) along with Asians (4.7% HBsAg positive). Among HIV-infected persons,
      38% were anti-HCV positive and 8.2% were HBsAg positive. Anti-HBc positivity was
      associated with anti-HCV positivity (aOR=4.58), anti-HIV positivity (aOR=2.94),
      syphilis infection (aOR=2.10), and previous incarceration (aOR=1.78). Anti-HCV
      positivity was associated with anti-HBc positivity (aOR=4.44), anti-HIV
      positivity (aOR=2.51), and previous incarceration (aOR=2.90). Jail entrants had
      high levels of HCV and HBV infection and HIV co-infection; HBV prevalence was
      comparable to previous prison studies, and HCV prevalence was lower than prison
      studies. Hispanics had an unexpectedly high rate of chronic hepatitis B infection
      and had the lowest rate of hepatitis B vaccination. The finding that hepatitis B
      vaccination coverage among jail entrants is lower than the general population,
      despite this population's increased risk for infection, highlights the need to
      support vaccination in jail settings.

PMID- 18622706
TI  - Growth hormone receptor modulators.
AB  - Growth hormone (GH) regulates somatic growth, substrate metabolism and body
      composition. Its actions are elaborated through the GH receptor (GHR). GHR
      signalling involves the role of at least three major pathways, STATs, MAPK, and
      PI3-kinase/Akt. GH receptor function can be modulated by changes to the ligand,
      to the receptor or by factors regulating signal transduction. Insights on the
      physico-chemical basis of the binding of GH to its receptor and the stoichiometry
      required for activation of the GH receptor-dimer has led to the development of
      novel GH agonists and antagonists. Owing to the fact that GH has short half-life,
      several approaches have been taken to create long-acting GHR agonists. This
      includes the pegylation, sustained release formulations, and ligand-receptor
      fusion proteins. Pegylation of a GH analogue (pegvisomant) which binds but not
      activate signal transduction forms the basis of a new successful approach to the
      treatment of acromegaly. GH receptors can be regulated at a number of levels, by
      modifying receptor expression, surface availability and signalling. Insulin,
      thyroid hormones and sex hormones are among hormones that modulate GHR through
      some of these mechanisms. Estrogens inhibit GH signalling by stimulating the
      expression of SOCS proteins which are negative regulators of cytokine receptor
      signalling. This review of GHR modulators will cover the effects of ligand
      modification, and of factors regulating receptor expression and signalling.

PMID- 18622709
TI  - Racial and geographic differences in mammography screening in St. Louis City: a
      multilevel study.
AB  - To examine racial differences in mammography use and its determinants in the City
      of St. Louis, MO, USA, we recruited women age 40 or older using random-digit
      dialing to (1) examine the difference in mammography use between white women and
      African American women and (2) identify individual- and census-tract-level risk
      factors of nonadherence to mammography. During telephone interviews, we inquired
      about mammography use and several demographic, psychosocial, and health behavior
      variables. We determined the residential census tracts of study subjects using a
      geographic information system. The rate of mammography use was 68.0% among white
      women and 74.7% among African American women (P = 0.022). African American women
      were more likely to have mammograms than white woman (adjusted odds ratio [OR] =
      1.71; 95% confidence interval [CI] = 1.09-2.69). System-level barriers to
      mammography and heavy smoking were associated with lower mammography use among
      both white and African American women. Personal-experience barriers to
      mammography and no physician recommendation also were independently associated
      with mammography use among white women. White women residing within a historic
      geographic cluster area of late-stage breast cancer were less likely to have
      mammograms (adjusted OR = 0.42, 95% CI = 0.22-0.80), while African American women
      residing within a historic geographic cluster area of late-stage breast cancer
      were equally likely to have mammograms (adjusted OR = 0.79, 95% CI = 0.28-2.24).
      Neither individual- nor census-tract-level socioeconomic status was associated
      with mammography screening. These findings suggest that there may be a greater
      need for increasing mammography use among white women, especially in the historic
      cluster area of late-stage breast cancer in St. Louis.

PMID- 18622708
TI  - HIV prevention services received at health care and HIV test providers by young
      men who have sex with men: an examination of racial disparities.
AB  - We investigated whether there were racial/ethnic differences among young men who
      have sex with men (MSM) in their use of, perceived importance of, receipt of, and
      satisfaction with HIV prevention services received at health care providers (HCP)
      and HIV test providers (HTP) that explain racial disparities in HIV prevalence.
      Young men, aged 23 to 29 years, were interviewed and tested for HIV at randomly
      sampled MSM-identified venues in six U.S. cities from 1998 through 2000. Analyses
      were restricted to five U.S. cities that enrolled 50 or more black or Hispanic
      MSM. Among the 2,424 MSM enrolled, 1,522 (63%) reported using a HCP, and 1,268
      (52%) reported having had an HIV test in the year prior to our interview. No
      racial/ethnic differences were found in using a HCP or testing for HIV. Compared
      with white MSM, black and Hispanic MSM were more likely to believe that HIV
      prevention services are important [respectively, AOR, 95% confidence interval
      (CI): 3.0, 1.97 to 4.51 and AOR, 95% CI: 2.7, 1.89 to 3.79], and were more likely
      to receive prevention services at their HCP (AOR, 95% CI: 2.5, 1.72 to 3.71 and
      AOR, 95% CI: 1.7, 1.18 to 2.41) and as likely to receive counseling services at
      their HTP. Blacks were more likely to be satisfied with the prevention services
      received at their HCP (AOR, 95% CI: 1.7, 1.14 to 2.65). Compared to white MSM,
      black and Hispanic MSM had equal or greater use of, perceived importance of,
      receipt of, and satisfaction with HIV prevention services. Differential
      experience with HIV prevention services does not explain the higher HIV
      prevalence among black and Hispanic MSM.

PMID- 18622710
TI  - Reduction of pollutants in pulp paper mill effluent treated by PCP-degrading
      bacterial strains.
AB  - Two PCP-degrading bacterial strains, Bacillus cereus (ITRC-S6) and Serratia
      marcescens (ITRC-S7) were used for the treatment of pulp and paper mill effluent
      at conditions; 1.0% glucose and 0.5% peptone at 30 +/- 1 degrees C at 120 rpm for
      168 h of incubation. These two bacterial strains effectively reduced colour (45
      52%), lignin (30-42%), BOD (40-70%), COD (50-60%), total phenol (32-40%) and PCP
      (85-90%) within 168 h of incubation. However, the highest reduction in colour
      (62%), lignin (54%), BOD (70%), COD (90%), total phenol (90%) and PCP (100%) was
      recorded by mixed culture treatment. The bacterial mechanism for the degradation
      of pulp and paper mill effluent may be explained by an increase in the cells
      biomass using added co-substrates resulting liberation of significant amount of
      chloride due to bacterial dechlorination of chlorolignins and chlorophenols this
      showed reduction in colour, lignin and toxicity in the effluent. Further, GC-MS
      analysis of ethyl acetate-extractable compounds from treated pulp paper mill
      effluent reinforces the bacterium capability for the degradation of lignin and
      pentachlorophenol, as many aromatic compounds such as 2-chlorophenol, 2, 4, 6
      trichlorophenol and tetrachlorohydroquinone, 6-chlorohydroxyquinol and
      tetrachlorohydroquinone detected which were not present in the untreated
      effluent.

PMID- 18622711
TI  - Relationship between land use and groundwater quality in six districts in the
      eastern region of Ghana.
AB  - The chemical quality of groundwater in six district of the eastern region beneath
      the different types of land use areas of Ghana was examined to evaluate the
      effects of human activities on groundwater. Analyses indicate that groundwater in
      the studied area is fresh and generally suitable for most uses. The groundwater
      is generally characterised by a chemical facies of Ca-HCO3-, Na-Cl and mixed Na
      Ca-HCO3 types and is weakly mineralised. Anthropogenic disturbances have had and
      continue to have an impact on the aquatic ecosystem of Ghana. High concentration
      of Cl- and TDS were found in wells in high residential areas while the highest
      levels of Na, Ca, SO4(2-) and NO3- were found in agricultural and high density
      residential areas. About 50% of boreholes sampled have elevated level of NO3(-)-N
      emanating from agricultural runoff.

PMID- 18622712
TI  - Dynamics of phytoplankton in relation to physico-chemical factors of Almatti
      reservoir of Bijapur District, Karnataka State.
AB  - The present investigation deals with limnobiotic status of the Almatti reservoir
      from February, 2003 to January, 2005. The study revealed that there exists a
      fluctuations of the physical factors viz., rainfall, humidity, air and water
      temperature, pH and electrical conductivity (EC), and chemical factors viz.,
      dissolved oxygen (DO), free carbon dioxide, total alkalinity, total hardness,
      calcium, magnesium, chloride, nitrate, phosphate, sulphate, bicarbonate and total
      dissolved solids (TDS). From the data it was also apparent that correlations
      between the physico-chemical factors and dynamics of phytoplankton could be seen.
      The simple correlation coefficient test revealed that the cyanophytes number was
      positively correlated with DO, nitrate, phosphate and negatively significant with
      total hardness, total alkalinity, EC, calcium, magnesium, sulphate, bicarbonate
      and TDS. They are inversely correlated with pH, chloride, rainfall and humidity.
      Bacillariphyceae are correlated with total alkalinity, bicarbonates, magnesium
      and TDS, whereas inverse correlation was found with rainfall, humidity, pH and
      phosphate. Desmids showed positive correlation with nitrates, while it was
      inversely correlated with chloride, rainfall and humidity. Dinophytes density was
      positively correlated with total alkalinity, EC, total hardness, calcium,
      bicarbonate, while it showed inverse correlation with rainfall, humidity and
      phosphate. However, it is obvious that the absence of significant difference
      between sampling stations for all these parameters in the Almatti reservoir
      indicated fairly homogeneous conditions and the water quality is also found to be
      homogeneous.

PMID- 18622714
TI  - Analysis of integrated animal-fish production system under subtropical hill agro
      ecosystem in India: growth performance of animals, total biomass production and
      monetary benefit.
AB  - The present study assessed the benefits of integration of animals with fish
      production in optimizing the bio mass production from unit land in subtropical
      hill agro ecosystem. Hampshire pigs and Khaki Campbell ducks were integrated with
      composite fish culture. The pig and duck excreta were directly allowed into the
      pond and no supplementary feed was given to fish during the period of study. The
      average levels of N, P and K in dried pig and duck manure were 0.9, 0.7 and 0.6
      per cent and 1.3, 0.6 and 0.5 per cent, respectively. The average body weight of
      pig and duck at 11 months age was 90 and 1.74 kg with an average daily weight
      gain of 333.33 and 6.44 g, respectively. The fish production in pig-fish and duck
      fish systems were 2209 and 2964 kg/ha, respectively while the fish productivity
      in control pond was only 820 kg/ha. The total biomass (animal and fish)
      production was higher (p<0.05) in commercial feeding system compared to the
      traditional system, however the input/output ratio was 1:1.2 and 1:1.55 for
      commercial and traditional systems, respectively. It was inferred that the total
      biomass production per unit land was high (p<0.05) when animal and fish were
      integrated together.

PMID- 18622713
TI  - Rotavirus diarrhea in bovines and other domestic animals.
AB  - Rotavirus diarrhea is the major cause of death of millions of children in
      developing countries besides causing economically significant malady in neonates
      of many domestic animals. In neonates, the infection is non-viremic, have very
      short incubation period, and manifests profuse diarrhea and severe dehydration.
      Concurrent infection with secondary pathogens may augment the disease severity.
      Diarrhea occurs due to virus-mediated destruction of absorption efficient
      enterocytes, activation of enteric nervous system, or due to a rotavirus
      enterotoxin. Diagnosis of the infection relies on conventional techniques like
      isolation in MA 104 cell lines, electron microscopy, electro-pherotyping, and
      various serological tests. Presently, diagnosis and molecular typing is performed
      using serotype specific RT-PCR, sequencing or genomic hybridization techniques.
      As the rotaviruses are known to exhibit extreme genetic diversity and outplay
      disinfection procedures, eradication of the pathogen is often difficult. Hence,
      for prevention, good management practices coupled with vaccination of dam for
      protecting young ones, has to be practiced. Recently, new generation prophylactic
      strategies including DNA vaccines, subunit vaccines, virus-like particles (VLPs)
      and edible vaccines have been found to induce sufficient levels of passive
      immunity. Aside to the infection in animals, zoonotic significance of the animal
      rotaviruses has to be further unearthed. In this review, efforts have been made
      to highlight the importance and prevalence of the disease in bovines, its
      pathogenesis along with preventive measures, salient features of rotaviruses and
      their inter-species transmission abilities, zoonotic implications, and a concise
      account of the infection in various domestic animals and poultry.

PMID- 18622715
TI  - Effects of age and jet lag on D-galactose induced aging process.
AB  - Chronic administration of D-galactose (D-gal) is a useful method for establishing
      a model of natural aging. However, whether animal age or jet lag influences the D
      gal-induced aging process has not been investigated. To clarify these issues, ICR
      male mice were given a daily injection of D-gal (500 mg/kg bw) for 7 wks. D-gal
      treatment caused a significant decrease only in the transcript level of Cat gene
      in the 6-wk-old mice, whereas it significantly reduced the expression of Cat and
      Sod1 genes and of Cat, Gpx1, Sod1 and Sod2 genes in the 12- and 22-wk-old group,
      respectively, suggesting that D-gal induced aging process was greatly dependent
      on the age of mice. Mice receiving both D-gal and jet lag exhibited larger
      decreases in the expression levels of above four genes in liver as compared with
      that of either group singly, indicating a synergistic effect of jet lag and D-gal
      on the aging process.

PMID- 18622716
TI  - Isolation of Candida dubliniensis for the first time in Cali, Colombia, and its
      identification with phenotyping methods.
AB  - Candida dubliniensis is an emerging pathogenic yeast isolated mainly from the
      oral cavity of HIV-infected patients. The close phenotypic and genotypic
      relationship between C. albicans and C. dubliniensis has led to incorrectly
      identifying isolates of C. dubliniensis as C. albicans. The oral cavities of 107
      diabetic patients were studied in Cali, Colombia, and 72 colonies of Candida,
      with shades of green on CHROMagar Candida culture media, were obtained. Various
      phenotypic tests were carried out, which included germ tube formation and
      production of chlamydospores on corn meal Agar. Additionally, growth studies were
      carried out at 42 degrees C and 45 degrees C and on Sabouraud agar with 6.5%,
      sodium chloride. Identification of C. dubliniensis with these tests was confirmed
      with API 20C Aux. We identified 65 and 7 colonies of C. albicans and C.
      dubliniensis, respectively. This is the first time that C. dubliniensis is
      identified with phenotypic methods in Colombia.

PMID- 18622717
TI  - Bipolaris hawaiiensis keratomycosis and endophthalmitis.
AB  - Following trauma with rice stalk to the left eye, corneal ulcer with abscess and
      hypopyon developed in an immunocompetent male. Direct examination of the corneal
      scrapings revealed septate, branched fungal hyphae. Bipolaris hawaiiensis was
      isolated after culture on blood agar and Sabouraud dextrose agar. Because of
      delay in diagnosis and appropriate treatment, the patient developed
      endophthalmitis needing evisceration.

PMID- 18622718
TI  - Limestone dissolution induced by fungal mycelia, acidic materials, and carbonic
      anhydrase from fungi.
AB  - Microorganisms influence the dissolution of a number of minerals. Limestone is
      one of the most abundant rock types in karst areas, and is predominantly calcium
      carbonate. Two types of experimental systems were designed in this paper, to make
      comparisons of limestone dissolution rate among the acidic materials and
      extracellular carbonic anhydrase (CA) excreted by fungi and the enwrapping effect
      of fungal mycelia. One was the simulated experimental system containing
      microorganisms. Another was the simulated experimental system without
      microorganisms. Results of previous experiment indicated that the acidic
      materials and CA like enzymatic materials excreted by fungi and the enwrapping
      effect of fungal mycelia were important factors influencing limestone
      dissolution. In the three factors mentioned above, the dissolution effect was
      mycelia enwraping effect>acidic dissolution effect>CA enzymatic effect. The
      results of the second experiment demonstrated further that the limestone
      dissolution effect of the acidic materials excreted by fungi was stronger than
      that of CA excreted by fungi. Nevertheless, CA still played an important role in
      promoting the dissolution of limestone.

PMID- 18622719
TI  - Comparison of glutathione S-transferase activity and concentration in aflatoxin
      producing and their non-toxigenic counterpart isolates.
AB  - In this study, two techniques were used to compare the specific activity and
      total concentration of mycelial glutathione S-transferase (GST) in fungal strains
      isolated from natural sources. The fungi identified as Aspergillus parasiticus
      and Aspergillus flavus have been divided into two groups based on their ability
      to produce aflatoxins. Altogether 26 fungi were isolated, among which 12 were
      capable of producing varying levels of aflatoxin and 14 were proved to be non
      toxigenic. GST specific activity in mycelial preparation was measured
      spectrophotometrically using 2,1-chloro-2,4-dinitrobenzene as the substrate. The
      results showed that the mean GST activity in toxigenic isolates was 25.06 +/- 9.8
      micromol/mg protein/min which was 2.8-fold greater than that measured in non
      toxigenic isolates (8.84 +/- 5.5 micromol/mg protein/min). Moreover, the GST
      concentration was compared in toxigenic and non-toxigenic isolates using an
      Enzyme Linked Immunosorbent Assay based on antigen (fungal preparation) and
      antibody (antibody produced against fungal GST in rabbit). The results of ELISA
      showed that the mean GST level in toxigenic and non-toxigenic fungi was 1.17 +/-
      0.55 and 0.40 +/- 0.24, respectively. These results further confirm that the
      aflatoxin production in the fungal strains is correlated with GST expression and
      using ELISA, it is possible to discriminate aflatoxin-producing fungi from their
      non-toxigenic counterparts.

PMID- 18622720
TI  - Combined effects of niacin and chromium treatment on vascular endothelial
      dysfunction in hyperlipidemic rats.
AB  - Combined treatment with niacin and chromium has been found to have a protective
      effect against oxidative damage to different tissues of hyperlipidemic rats. But
      its effects on vascular endothelial dysfunction are less clear. This study was
      performed to investigate the effect of combined treatment with niacin and
      chromium on vascular endothelial dysfunction, with the aim of gaining insight to
      the mechanisms by detecting the expression levels of ox-LDL and LOX-1. Twenty
      four male, 4-week-old Wistar rats were randomly divided into three groups:
      control group (CG; n = 8), high-fat group (HF; n = 8), and drug control group
      (DG; n = 8). In CG group, rats were fed with pellet chow. In HF group, rats were
      fed with high-fat diet for 12 weeks. In DG group, rats were fed with the same
      high-fat diet and treated with CrCl(3) x 6 H(2)O (250 microg/kg days) and niacin
      (100 mg/kg days) by gavage technique for 12 weeks. At the end of the 12th week,
      samples from aorta and blood were collected. In HF group, the serum levels of
      total cholesterol (TC), low-density lipoprotein (LDL), oxidized low-density
      lipoprotein (ox-LDL) and endothelin (ET) were higher, whereas the levels of high
      density lipoprotein (HDL), serum NO were lower than those in CG group. The levels
      of serum TC, LDL, ox-LDL and ET decreased and HDL, NO levels increased in DG
      group when compared with HF group. The levels of LOX-1, ICAM-1 were also observed
      in abdominal artery. In HF group, the protein and mRNA expression of LOX-1, ICAM
      1 were elevated comparing with CG group. In DG group, the protein and mRNA
      expression of LOX-1, ICAM-1 were decreased obviously, but still differed
      significantly from those in CG group. ox-LDL was related positively to TC, LDL,
      ET, ICAM-1 and LOX-1, but related negatively to NO and HDL. These findings
      indicated that combined treatment with niacin and chromium has potential
      therapeutic protection of endothelial function by down-regulating ox-LDL/LOX-1
      signaling pathway.

PMID- 18622721
TI  - An assessment of the construct validity of the descriptive system for the ICECAP
      capability measure for older people.
AB  - BACKGROUND: The index of capability (ICECAP) was developed using in-depth
      interviews with 40 older people and comprises five attributes: attachment,
      security, enjoyment, role and control. This paper explores the construct validity
      of these five capability attributes. METHODS: An interview survey was conducted
      with individuals aged 65 and over located across the UK. Data were analysed in
      six categories (socio-demographic variables and general well-being, contact with
      others, health, nature of the locality and environment, social support and
      participation) using chi-squared tests (for categorical variables) or one-way
      analysis of variance (for continuous variables). RESULTS: About 315 individuals
      were interviewed (response rate 66%). Relationships were generally as anticipated
      with, for example: strong relationships between age and capability and well-being
      and capability, but no relationships between capability and either sex or social
      class; strong relationships between physical measures of health and role,
      enjoyment and control, and between mental health measures and attachment and
      enjoyment. CONCLUSIONS: This study provides some early evidence for the construct
      validity of the ICECAP measure. Where anticipated relationships were not observed
      this might in part be explained in that the ICECAP index asks about capability,
      but the factors with which associations were examined were largely and inevitably
      measures of function.

PMID- 18622722
TI  - An assessment of factorial structure and health-related quality of life in
      problem drug users using the Short Form 36 Health Survey.
AB  - AIMS: To confirm the factorial structure of the Short Form 36 Health Survey (SF
      36) in problem drug users and to compare their health-related quality of life
      (HRQOL) with general Dutch population norms. METHOD: Data of 394 participants
      from the Amsterdam Cohort Study among drug users, who had completed once the SF
      36 standard form (4 weeks recall) between February and August 2005, were
      analyzed. The factorial structure of the SF-36 was investigated by confirmatory
      factor analysis. Subsequently, sum scores of the eight SF-36 health dimensions
      were converted into z-scores by standardizing them with the mean and standard
      deviation of the corresponding general Dutch population age and gender group.
      RESULTS: The factor structure was acceptable and also comparable with previous
      findings. Compared with the general population, participants had significantly
      lower z-scores on all of the eight SF-36 dimensions, with largest deviations in
      social functioning (M = -1.13) and mental health (M = -1.01), and smallest
      deviations in bodily pain (M = -0.32). CONCLUSION: The results corroborate the
      factorial structure and reliability of the answers of problem drug users to the
      SF-36. Their HRQOL was low, even though it was assessed irrespective of substance
      abuse treatment settings.

PMID- 18622723
TI  - Indian mustard aquaporin improves drought and heavy-metal resistance in tobacco.
AB  - An aquaporin cDNA BjPIP1 isolated from heavy-metal accumulator Indian mustard
      (Brassica juncea L.) encodes a 286-residue protein. The deduced amino acid
      sequence of BjPIP1 with six putative transmembrane domains showed highest
      identity (85-99%) to PIP1 subfamily members. Semi-quantitative RT-PCR analysis
      revealed that BjPIP1 transcripts were more abundantly expressed in roots compared
      to aerial parts of Indian mustard. However, the expression of BjPIP1 in leaves
      was up-regulated by drought, salt, low temperature, and heavy metal stress,
      suggesting that BjPIP1 was involved in resistance to abiotic stresses. BjPIP1
      under the control of 35S promoter was introduced into tobacco mediated with
      Agrobacterium tumefaciens, the transgenic tobacco exhibited a lower water loss
      rate, a decreased transpiration rate, and stomatal conductance compared to the
      wild-type plants under osmotic stress, indicating that BjPIP1 might enhance plant
      drought resistance by decreasing transpiration via reducing stomatal conductance.
      Furthermore, overexpression of BjPIP1 in tobacco enhanced Cd resistance of root
      growth, and lowered transpiration rate and stomatal conductance upon Cd exposure,
      suggesting that BjPIP1 might increase heavy-metal resistance by maintaining
      reasonable water status in tobacco. Moreover, the BjPIP1-overexpressing plants
      showed higher activities of antioxidative enzymes, and lower level of electrolyte
      leakage and malondialdehyde content under Cd stress, indicating BjPIP1 might
      enhance the antioxidative activity and membrane integrity in transgenic plants.
      Taken together, these results suggested that BjPIP1 might improve plant heavy
      metal resistance through alleviating water deficit and oxidative damage induced
      by metal ions.

PMID- 18622728
TI  - Combined Impella and intra-aortic balloon pump support to improve macro- and
      microcirculation: a clinical case.

PMID- 18622729
TI  - Acute myocardial infarction associated with use of herbal medication.

PMID- 18622730
TI  - Dietary supplementation with Astragalus polysaccharide enhances ileal
      digestibilities and serum concentrations of amino acids in early weaned piglets.
AB  - Two experiments were conducted to evaluate the effects of dietary supplementation
      with Astragalus polysaccharide (APS) on growth performance, apparent ileal
      digestibilities (AID) of amino acids (AA), and their serum concentrations in
      early weaned piglets. In Exp. 1, 60 pigs were weaned at 21 days of age (BW 7.35
      +/- 0.23 kg) and allocated to three treatments (20 pigs/treatment), representing
      supplementing 0.0% (control), 0.02% colistin (antibiotic), or 0.1% APS to a corn-
      and soybean meal-based diet. Average daily gain (ADG), average daily feed intake
      (ADFI), and feed/gain ratio (F/G) were measured weekly. Blood samples were
      obtained from five pigs selected randomly from each treatment for the measurement
      of serum free AA concentrations on days 7, 14, and 28. In Exp. 2, 12 pigs were
      weaned at 21 day of age (BW 7.64 +/- 0.71 kg), assigned to three treatment groups
      as in Exp. 1, and surgically fitted with a simple T-cannula at the terminal
      ileum. Ileal digesta samples were obtained for the measurement of AID of AA on
      days 7, 14 and 28. Dietary APS did not affect ADFI, but enhanced (P < 0.05) ADG
      by 11 and 4.4%, and improved F/G by 5.6 and 8.4%, respectively, compared with the
      control and antibiotic groups. Addition of APS to the diet increased AID and
      serum concentrations of most nutritionally essential and non-essential AA
      (including arginine, proline, glutamate, lysine, methionine, tryptophan, and
      threonine) on days 14 and 28. Circulating levels of total AA were affected by the
      age of pigs and treatment x time interaction. Collectively, these findings
      indicate that APS may ameliorate the digestive and absorptive function and
      regulate AA metabolism to beneficially increase the entry of dietary AA into the
      systemic circulation, which provide a mechanism to explain the growth-promoting
      effect of APS in early weaned piglets.

PMID- 18622724
TI  - Corneal epithelial stem cells: deficiency and regulation.
AB  - The corneal epithelium is continuously renewed by a population of stem cells that
      reside in the corneoscleral junction, otherwise known as the limbus. These limbal
      epithelial stem cells (LESC) are imperative for corneal maintenance with
      deficiencies leading to in-growth of conjunctival cells, neovascularisation of
      the corneal stroma and eventual corneal opacity and visual loss. One such disease
      that has traditionally been thought to be due to LESC deficiency is aniridia, a
      pan-ocular congenital eye disease due to mutations in the PAX6 gene. Corneal
      changes or aniridia related keratopathy (ARK) seen in aniridia are typical of
      LESC deficiency. However, the pathophysiology behind ARK is still ill defined,
      with current theories suggesting it may be caused by a deficiency in the stem
      cell niche and adjacent corneal stroma, with altered wound healing responses also
      playing a role (Ramaesh et al, International Journal of Biochemistry & Cell
      Biology 37:547-557, 2005) or abnormal epidermal differentiation of LESC (Li et
      al., The Journal of Pathology 214:9, 2008). PAX6 is considered the master control
      gene for the eye and is required for normal eye development with expression
      continuing in the adult cornea, thus inferring a role for corneal repair and
      regeneration (Sivak et al., Developments in Biologicals 222:41-54, 2000). Studies
      of models of Pax6 deficiency, such as the small eyed (sey) mouse, should help to
      reveal the intrinsic and extrinsic mechanisms involved in normal LESC function.

PMID- 18622731
TI  - Maize cytosolic NADP-malic enzyme (ZmCytNADP-ME): a phylogenetically distant
      isoform specifically expressed in embryo and emerging roots.
AB  - Two maize plastidic NADP-malic enzyme isoforms have been characterized: the
      bundle sheath-located photosynthetic isoform (ZmC(4)-NADP-ME) and a
      constitutively expressed one (Zm-nonC(4)-NADP-ME). In this work, the
      characterization of the first maize cytosolic NADP-ME (ZmCytNADP-ME) is
      presented, which transcript is exclusively found in embryo and emerging roots.
      ZmCytNADP-ME expression in roots decreases with development, while Zm-nonC ( 4 ) 
      NADP-ME increases concomitantly. On the other hand, ZmCytNADP-ME accumulation is
      differentially modulated by several stress conditions and shows coordination with
      that of Zm-nonC ( 4 ) -NADP-ME in maize young roots. Recombinant ZmCytNADP-ME
      displays clearly distinct kinetic parameters and metabolic regulation than the
      plastidic isoforms. The particular properties and the specific-expression pattern
      of this novel isoform suggest that it may be involved in the control of cytosolic
      malate levels in emerging roots, e.g. during hypoxia. ZmCytNADP-ME is
      phylogenetically related to other cytosolic mono and dicot NADP-MEs, and data
      indicate that it belongs to an ancestral unique group among plant NADP-MEs.

PMID- 18622732
TI  - The expression pattern of plasma membrane aquaporins in maize leaf highlights
      their role in hydraulic regulation.
AB  - Leaves are key organs for evaporation and photosynthesis and play a crucial role
      in plant growth and development. In order to function properly, they need to
      maintain a balanced water content. Water movement through a leaf occurs by a
      combination of different pathways: water can follow an apoplastic route through
      the cell wall or a cell-to-cell route via the symplastic and transcellular paths.
      As aquaporins (AQPs) play an important role in regulating transcellular water
      flow and CO(2) conductance, studies on AQP mRNA and protein expression in leaves
      are essential to better understand their role in these physiological processes.
      Here, we quantified and localized the expression of Zea mays plasma membrane
      aquaporins (ZmPIPs, plasma membrane intrinsic proteins) in the leaf using
      quantitative RT-PCR and immunodetection. All ZmPIP genes except ZmPIP2;7 were
      expressed in leaves. Expression was found to be dependent on the developmental
      stage of the leaf tissue, with, in general, an increase in expression at the end
      of the elongation zone and a decrease in mature leaf tissue. These data
      correlated with the cell water permeability, as determined using a protoplast
      swelling assay. The diurnal expression of ZmPIPs was also investigated and
      expression was found to be higher during the first hours of the light period than
      at night. Immunocytochemical localization of four ZmPIP isoforms indicated that
      they are involved in leaf radial water movement, in particular in vascular
      bundles and the mesophyll.

PMID- 18622734
TI  - A retrospective study on the prevalence of ostrich carcass and organ
      condemnations in Botswana.
AB  - A retrospective study on the prevalence of ostrich carcass and organ
      condemnations in Botswana was conducted by reviewing meat inspection records
      available at the Botswana Ostrich Company Abattoir in Gaborone for the 3 year
      period that the abattoir had been in operation. The most frequently condemned
      organs were lung (85.1%), liver (8%), intestine (3.3%), heart (2.7%) and kidney
      (0.8%). The most frequently encountered macroscopic findings were contamination
      (80%), congestion (10%), enteritis (3%), haemorrhage (2%), pigmentation (2%),
      white spots on the liver (1%) and peritonitis (1%). The frequencies of the
      various macroscopic findings on all the organs increased over the 3 years of the
      study. Ninety-five percent (95%) of the findings were all abattoir associated,
      especially the external contamination of organs (80%). The 5% that were acquired
      during the lifetime of the birds included enteritis, peritonitis and white spots
      on the liver. No whole carcass condemnations or carcass trimmings were recorded,
      nor where there any zoonotic causes of condemnation.

PMID- 18622733
TI  - Heterologous expression of a plastid EF-Tu reduces protein thermal aggregation
      and enhances CO2 fixation in wheat (Triticum aestivum) following heat stress.
AB  - Heat stress is a major constraint to wheat production and negatively impacts
      grain quality, causing tremendous economic losses, and may become a more
      troublesome factor due to global warming. At the cellular level, heat stress
      causes denaturation and aggregation of proteins and injury to membranes leading
      to alterations in metabolic fluxes. Protein aggregation is irreversible, and
      protection of proteins from thermal aggregation is a strategy a cell uses to
      tolerate heat stress. Here we report on the development of transgenic wheat
      (Triticum aestivum) events, expressing a maize gene coding for plastidal protein
      synthesis elongation factor (EF-Tu), which, compared to non-transgenic plants,
      display reduced thermal aggregation of leaf proteins, reduced heat injury to
      photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation after
      exposure to heat stress. The results support the concept that EF-Tu ameliorates
      negative effects of heat stress by acting as a molecular chaperone. This is the
      first demonstration of the introduction of a plastidal EF-Tu in plants that leads
      to protection against heat injury and enhanced photosynthesis after heat stress.
      This is also the first demonstration that a gene other than HSP gene can be used
      for improvement of heat tolerance and that the improvement is possible in a
      species that has a complex genome, hexaploid wheat. The results strongly suggest
      that heat tolerance of wheat, and possibly other crop plants, can be improved by
      modulating expression of plastidal EF-Tu and/or by selection of genotypes with
      increased endogenous levels of this protein.

PMID- 18622735
TI  - Comparative efficacy of standard AGID and precipitinogen inhibition test with
      monoclonal antibodies based competitive ELISA for the serology of Peste des
      Petits Ruminants in sheep and goats.
AB  - This project was conducted to investigate the comparative efficiency of
      competitive ELISA (cELISA), standard Agar Gel Immunodiffusion Test (AGID) and
      Precipitinogen Inhibition Test (PIT) for the diagnosis of Peste des Petits
      Ruminants (PPR) in Pakistan. To deal with this, serum samples from 198 sheep and
      82 goats were collected from three different government livestock farms and all
      the samples were run simultaneously with the three serological tests. The samples
      found positive for PPR antibodies through cELISA, AGID and PIT were 96 (34.2%),
      60 (21.4%) and 72 (25.7%), respectively. Kappa statistics were applied to
      evaluate the concordance between the laboratory-based test (cELISA) and field
      based tests (AGID and PIT). Kappa statistics scores for cELISA versus AGID and
      PIT were 0.6343 (95% Confidence Interval CI 0.5231-0.7456) and 0.7134 (95%
      Confidence Interval CI 0.5987-0.8281), respectively, which indicate a
      "substantial" agreement between cELISA and AGID and "significant" agreement
      between cELISA and PIT. AGID and PIT revealed relative diagnostic sensitivities
      with cELISA of 59.3% and 69.7% and relative diagnostic specificities of 98.3% and
      97.2%, respectively. The data suggested that for mass screening and control of
      PPR, these serological tests proved practical in the absence of cELISA since they
      have high relative diagnostic specificities and a satisfactory relative
      diagnostic sensitivities.

PMID- 18622736
TI  - Deficiency of the cystine-transporter gene, xCT, does not exacerbate the
      deleterious phenotypic consequences of SOD1 knockout in mice.
AB  - Because glutathione scavenges reactive oxygen species (ROS) and also donates
      electrons to antioxidative systems, it may compensate for the oxidative stress
      caused by SOD1 deficiency. The cystine/glutamate transporter, which consists of
      two proteins, xCT and 4F2hc, has been designated system x (c) (-) . This
      transporter system plays a role in the maintenance of glutathione levels in
      mammalian cells. In the present study, we created SOD1 (-/-); xCT (-/-) double
      knockout mice by intercrossing xCT-knockout and SOD1-knockout animals. We
      determined if the double-knockout mice express the phenotypic characteristics
      unique to SOD1 (-/-) mice-increased oxidative stress and the production of
      autoantibodies against erythrocytes. We also compared the phenotype of the double
      knockout mice with those of the single-knockout and wild-type mice. Although two
      major antioxidative systems were found to be defective in the SOD1 (-/-); xCT (-/
      ) mice, relative to the SOD1 (-/-) mice, no functional deficits were observed.
      Based on these results, it appears that defects in system x (c) (-) do not
      exacerbate the phenotypic consequences of SOD1 deficiency in postnatal mice under
      ordinary breeding conditions.

PMID- 18622737
TI  - Gramicidin A directly inhibits mammalian Na(+)/K (+)-ATPase.
AB  - The linear pentadecapeptide gramicidin A forms an ion channel in the lipid
      bilayer to selectively transport monovalent cations. Nevertheless, we have
      surprisingly found that gramicidin A directly inhibits mammalian Na(+)/K(+)
      ATPase. Gramicidin A inhibited ATP hydrolysis by Na(+)/K(+)-ATPase from porcine
      cerebral cortex at the IC(50) value of 8.1 microM, while gramicidin S was
      approximately fivefold less active. The synthetic gramicidin A analog lacking N
      terminal formylation and C-terminal ethanolamine exhibited a weaker inhibitory
      effect on the ATP-hydrolyzing activity of Na(+)/K(+)-ATPase than gramicidin A,
      indicating that these end modifications are necessary for gramicidin A to inhibit
      Na(+)/K(+)-ATPase activity. Moreover, Lineweaver-Burk analysis showed that
      gramicidin A exhibits a mixed type of inhibition. In addition to the most well
      studied ionophore activity, our present study has disclosed a novel biological
      function of gramicidin A as a direct inhibitor of mammalian Na(+)/K(+)-ATPase
      activity.

PMID- 18622738
TI  - Antilipolytic effect of calcium-sensing receptor in human adipocytes.
AB  - The extracellular calcium-sensing receptor (CaSR), a seven transmembrane G
      protein-coupled receptor, was cloned in 1993. Its activation was first associated
      to the regulation of calcium homeostasis; however, the presence in tissues
      unrelated with this role has revealed its participation in numerous other cell
      functions. We previously described CaSR expression in human adipocytes, and here
      we investigated the effect of its activation on adipocyte lipolytic activity by
      measuring glycerol release to the incubation medium. Treatment of adipocytes with
      CaSR agonists elicited an inhibitory effect on basal lipolysis, which was
      prevented by a CaSR antagonist. To further corroborate the antilipolytic effect
      of CaSR activation, lipolysis was evaluated under conditions that interfere with
      main antilipolytic regulatory pathways. Cells were preincubated with pertussis
      toxin (PT, a Gialpha protein inhibitor), the phosphatidylinositol 3 kinase (PI3K)
      inhibitors wortmannin and LY-294002 as well as the cAMP analog 8Br-cAMP, all of
      which influenced the antilipolytic effect of CaSR stimulation. In light of the
      current view of adipose tissue as an organ involved in whole-body metabolic
      control, the role of the CaSR modulating basal lipolysis elicits great interest,
      given its metabolic sensing capabilities due to the variety of ligands that
      regulate its activity, and its potential cross-talk with insulin and adipose
      tissue-secreted factors.

PMID- 18622739
TI  - Feasibility and toxicity of dose-dense adjuvant chemotherapy in older women with
      breast cancer.
AB  - INTRODUCTION: The objective of this study was to examine the feasibility and
      toxicity of adjuvant dose-dense chemotherapy in older women with breast cancer.
      METHODS: A search of the Memorial Sloan-Kettering Cancer Center (MSKCC) breast
      cancer database was performed to identify all patients age 60 and older who
      underwent an initial consultation with a breast medical oncologist between
      October 1, 2002 and June 28, 2005. Inclusion criteria were: (1) age > or = 60,
      (2) follow-up care obtained at MSKCC, (3) intent to treat with adjuvant dose
      dense AC-T (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 2 weeks
      for 4 cycles followed by paclitaxel 175 mg/m(2) every 2 weeks for 4 cycles, with
      white blood cell growth factor support). RESULTS: One hundred sixty-two patients
      (mean age 66, range 60-76) with breast cancer, stages I (n = 5), II (n = 111),
      and III (n = 46) according to the sixth edition of the AJCC staging system, were
      included in this analysis. Forty-one percent (n = 67) experienced a grade 3 or 4
      toxicity, 9% a grade 3 infection (n = 14), 6% grade 3 fatigue (n = 9), 5%
      neutropenic fever (n = 8), and 4% thromboembolic events (n = 7). Twenty-two
      percent (n = 36) did not complete the planned 8 cycles of treatment. There was no
      statistically significant association between age and either toxicity or
      treatment discontinuation. In multivariate analysis including age, pretreatment
      hemoglobin, and comorbidity, the presence of comorbidity (Charlson score > or =
      1) and a lower baseline hemoglobin score were associated with an increased risk
      of any grade 3 or 4 toxicity. CONCLUSIONS: We found that the risk of toxicity
      depended more on comorbid medical conditions and baseline hemoglobin value than
      age in this cohort of older adults receiving dose-dense adjuvant chemotherapy.

PMID- 18622740
TI  - Clonal diversity of Clintonia udensis Trautv. et Mey. populations and its
      correlation with ecological factors.
AB  - The clonal diversity of Clintonia udensis Trautv. et Mey. was detected by ISSR
      markers among 16 populations, and its correlation with ecological factors was
      analyzed as well in this work. Results showed that individuals (clonal ramets)
      per genotype were 1.12 and 1.149 at population and species levels, respectively,
      and that the 16 populations were all multiclonal. The detected genotypes were
      localized, without exception, within populations but demonstrated relatively high
      clonal differentiation among populations. The clonal diversity of the studied
      populations was high, with the average Simpson's index of 0.975, while the genets
      showed a clonal architecture of "guerilla". The population genetic diversities
      revealed by genet were consistent with those by ramet, further confirming their
      genetic differentiation among populations. And its genotype diversity within
      populations probably resulted largely from the frequent seedling regeneration and
      self-compatibility. In addition, the correlation analysis further revealed that,
      among the ecological factors, Simpson's index of C. udensis had a significant
      positive correlation (P<0.05) with pH values in the soil but not others.

PMID- 18622741
TI  - Dissection of genetic overlap of salt tolerance QTLs at the seedling and
      tillering stages using backcross introgression lines in rice.
AB  - QTLs for salt-tolerance (ST) related traits at the seedling and tillering stages
      were identified using 99 BC(2)F(8) introgression lines (IL) derived from a cross
      between IR64 (indica) as a recurrent parent and Binam (japonica) from Iran as the
      donor parent. Thirteen QTLs affecting survival days of seedlings (SDS), score of
      salt toxicity of leaves (SST), shoot K(+) concentration (SKC) and shoot Na(+)
      concentration (SNC) at the seedling stage and 22 QTLs underlying fresh weight of
      shoots (FW), tiller number per plant (TN) and plant height (PH) at the tillering
      stage were identified. Most QTLs detected at the tillering stage showed obvious
      differential expression to salt stress and were classified into three types based
      on their differential behaviors. Type I included 11 QTLs which were expressed
      only under the non-stress condition. Type II included five QTLs expressed in the
      control and the salt stress conditions, and three of them (QPh5, QPh8 and QTn9)
      had similar quantity and the same direction of gene effect, suggesting their
      expression was less influenced by salt stress. Type III included six QTLs which
      were detectable only under salt stress, suggesting that these QTLs were
      apparently induced by the stress. Thirteen QTLs affecting trait difference or
      trait stability of ILs between the stress and non-stress conditions were
      identified and the Binam alleles at all loci except QPh4, QTn2 and QFw2a
      decreased trait difference. The three QTLs less influenced by the stress and 13
      QTLs affecting trait stability were considered as ST QTLs which contributed to
      ST. Comparing the distribution of QTLs detected at the seedling and tillering
      stages, most (69%) of them were genetically independent. Only four were the same
      or adjacent regions on chromosomes 1, 2, 8 and 11 harboring ST QTLs detected at
      the two stages, suggesting that partial genetic overlap of ST across the two
      stages occurs. It is likely, therefore, to develop ST rice variety for both
      stages by pyramiding of ST QTLs of different stages or selection against the
      overlapping QTLs between the two stages via marker-assisted selection (MAS).

PMID- 18622742
TI  - High-nitrogen and low-irradiance can restrict energy utilization in
      photosynthesis of successional tree species in low subtropical forest.
AB  - Responses of photosynthesis and the partition of energy utilization to high
      nitrogen importation and high-light intensity in leaves of three dominant tree
      species of subtropical forest, including sun plant or early-successional species
      Schima superba, mesophyte or intermediate-successional species Canstanopsis
      hystrix, and shading-tolerant plant or late-successional species Cryptocarya
      concinna were studied by using the CO(2) exchange system and chlorophyll
      fluorescence method. Our results showed that, regardless of plant species, net
      photosynthetic rate (P (n)) was higher in high-nitrogen supply and high
      irradiance (HNHL) plants than in low-nitrogen supply and high irradiance (LNHL)
      plants, implying that low-nitrogen importation would limit P (n) of plants grown
      under high irradiance. However, high-nitrogen supply and low irradiance (HNLL)
      plants had a lower P (n). Insignificant change of quantum yield (F (v)'/F (m)')
      in opened PS II was found in leaves of HNHL, LNHL or HNLL plants of S. superba
      and C. hystrix, while a higher F (v)'/F (m)' occurred in HNHL plants of C.
      concinna in comparison with LNHL or HNLL plants. The HNHL plants of C. concinna
      also had a higher photochemical quantum yield (DeltaF/F (m)') than LNHL or HNLL
      plants, however no similar responses were found in plants of S. superba and C.
      hystrix (P <0.05). In the irradiance range of 0-2000 mumol photon.m(-2) .s(-1),
      the fraction of energy consumed by photochemistry (varphi (PSII)) was 18.2% in
      LNHL plants of S. superba which was higher than that in HNHL plants (P>0.05) and
      it was significantly higher than in HNLL plants (P<0.05). C. hystrix also had a
      similar response in varphi (PSII) to nitrogen supply and irradiance. Regardless
      of species HNLL plants had a significant varphi (PSII) and higher heat
      dissipation in light, and this effect was more severe in C. concinna than in S.
      superba or C. hystrix. The results may mean that high-nitrogen importation by
      nitrogen deposit and low irradiance caused by changing climate or air pollution
      would more severely restrict photosynthetic processes in the late-successional
      species C. concinna than in the early-successional species S. superba and
      intermediate-successional species C. hystrix. The continuous high-nitrogen
      precipitation in the future and the over cast mist or pollution smoke could
      induce late-successional species to degrade, however, early-successional species
      would be more adapted to competition for more resources to keep their dominance
      in ecosystems. In this sense, the zonal vegetation may accelerate degradation
      caused by high nitrogen precipitation and low irradiance, while the early
      successional and mesophytic vegetations can remain longer. Thus, nitrogen
      precipitation may play an important role in plant community succession.

PMID- 18622743
TI  - Construction and characterization of the transformation-competent artificial
      chromosome (TAC) libraries of Leymus multicaulis.
AB  - Transformation-competent artificial chromosome system is able to clone and
      transfer genes efficiently in plants. In order to clone genes highly tolerant to
      barley yellow dwarf virus (BYDV), Aphids, drought and salt from Leymus
      multicaulis, the two TAC genomic libraries I and II were constructed in vector
      pYLTAC17 and pYLTAC747H/sacB, which contain about 165000 and 236000 recombinant
      clones separately. The genome coverage of the two libraries was totally estimated
      to be about 3-5 haploid genome equivalents, as size selection of genomic DNA
      fragments was approximately from 9 to 300 kb. Clones of the genomic libraries
      were collected as bulked pools each containing 500 clones or so, stored in twelve
      96-deep-well plates and then were gridding in triplicate onto a high-density
      colony hybridization filter with a 3x3 pattern using a GeneTACtrade mark G3
      arraying robot after being transferred manually into three 384-well plates.
      Meanwhile 2501 and 2890 clones of Library in pYLTAC17 and in pYLTAC747H/sacB were
      stored individually in fourteen 384-well plates and then were automatically
      gridding in duplicate onto a high-density colony hybridization filter with a 6x6
      pattern after a replication of plates. Nineteen positive clones were detected by
      using the probe glutahione reductase gene of L. multicaulis. TAC libraries
      constructed here can be used to isolate genomic clones containing target genes,
      and to carry out genome walking for positional cloning. Once the target TAC
      clones were isolated, they could be immediately transferred into plant genomes
      with the Agrobacterium system.

PMID- 18622744
TI  - Polymorphisms of three gene-derived STS on pig chromosome 13q41 are associated
      with susceptibility to enterotoxigenic Escherichia coli F4ab/ac in pigs.
AB  - Neonatal diarrhea caused by enterotoxigenic Escherichia coli (ETEC) F4 is a
      common and serious disease, resulting in significant economical loss in the pig
      industry. The locus encoding ETEC F4 receptor has been mapped to pig chromosome
      (SSC) 13q41, and one of the most significantly linked markers is S0075. In this
      study, we selected three genes including SLC12A8, MYLK and KPNA1 from a
      chromosomal region flanking S0075 on SSC13 to develop pig specific sequence
      tagged sites (STS). Seven single nucleotide polymorphisms were identified in the
      three pig STS using DNA of four full-sib susceptible and resistant animals in a
      White Duroc x Erhualian intercross. All grandparents, parents and 755 offspring
      in the intercross were genotyped for three polymorphisms, including SLC12A8
      g.159A>G, MYLK g.1673A>G and KPNA1 g.306A>G. Family-based transmission
      disequilibrium test (TDT) revealed that all polymorphisms and the corresponding
      haplotypes are significantly associated with ETEC F4ab/ac (especially F4ac) brush
      border adhesion phenotypes, indicating that these polymorphism are in linkage
      disequlibrium with causal mutation(s) of the gene encoding ETEC F4ab/ac receptor.
      Our results strengthen the evidence for the involvement of SSC13q41 in high
      acquiring risk of ETEC F4ab/ac infection, and provide novel polymorphic markers
      for fine mapping of the ETEC F4ab/ac receptor locus.

PMID- 18622745
TI  - A novel function for the cellulose binding module of cellobiohydrolase I.
AB  - A homogeneous cellulose-binding module (CBM) of cellobiohydrolase I (CBHI) from
      Trichoderma pseudokoningii S-38 was obtained by the limited proteolysis with
      papain and a series of chromatographs filtration. Analysis of FT-IR spectra
      demonstrated that the structural changes result from a weakening and splitting of
      the hydrogen bond network in cellulose by the action of CBM(CBHI) at 40 degrees C
      for 24 h. The results of molecular dynamic simulations are consistent with the
      experimental conclusions, and provide a nanoscopic view of the mechanism that
      strong and medium H-bonds decreased dramatically when CBM was bound to the
      cellulose surface. The function of CBM(CBHI) is not only limited to locating
      intact CBHI in close proximity with cellulose fibrils, but also is involved in
      the structural disruption at the fibre surface. The present studies provided
      considerable evidence for the model of the intramolecular synergy between the
      catalytic domain and their CBMs.

PMID- 18622746
TI  - PrP mutants with different numbers of octarepeat sequences are more susceptible
      to the oxidative stress.
AB  - One of the physiological functions of cellular prion protein (PrP(C)) is believed
      to work as a cellular resistance to oxidative stress, in which the octarepeats
      region within PrP plays an important role. However, the detailed mechanism is
      less clear. In this study, the expressing plasmids of wild-type PrP (PrP-PG5) and
      various PrP mutants containing 0 (PrP-PG0), 9 (PrP-PG9) and 12 (PrP-PG12)
      octarepeats were generated and PrP proteins were expressed both in E. coli and in
      mammalian cells. Protein aggregation and formation of carbonyl groups were
      clearly seen in the recombinant PrPs expressed from E. coli after treatment of
      H(2)O(2). MTT and trypan blue staining assays revealed that the cells expressing
      the mutated PrPs within octarepeats are less viable than the cells expressing
      wild-type PrP. Statistically significant high levels of intracellular free
      radicals and low levels of glutathione peroxidase were observed in the cells
      transfected with plasmids containing deleted or inserted octarepeats. Remarkably
      more productions of carbonyl groups were detected in the cells expressing PrPs
      with deleted and inserted octarepeats after exposing to H(2)O(2). Furthermore,
      cells expressing wild-type PrP showed stronger resistant activity to the
      challenge of H(2)O(2) at certain extent than the mutated PrPs and mock. These
      data provided the evidences that the octarepeats number within PrP is critical
      for maintaining its activity of antioxidation. Loss of its protective function
      against oxidative stress may be one of the possible pathways for the mutated PrPs
      to involve in the pathogenesis of familial Creutzfeldt-Jacob diseases.

PMID- 18622747
TI  - Mammalian target of rapamycin pathway inhibition enhances the effects of 5-aza-dC
      on suppressing cell proliferation in human gastric cancer cell lines.
AB  - The present study aimed to evaluate the relationship between mTOR signaling
      pathway and DNA methylation in cell survival, cell cycle, gene expression and
      protein level on human gastric cancer cells. Human gastric cancer cell lines,
      MKN45 and SGC7901 were treated with 5-aza-dC, rapamycin and/or LY294002. Cell
      viability was analyzed by MTT. Cell cycle distribution was evaluated by flow
      cytometry (FCM). The transcription level of PTEN and p27 ( Kip1 ) genes was
      detected by using real-time PCR. Protein expressions were detected by Western
      blotting. We found that cell viability was moderately reduced when treated with 5
      aza-dC alone, but remarkably reduced when mTOR pathway was inhibited together
      (P<0.01). mTOR inhibition enhances the effects of 5-aza-dC on arresting cell
      cycle at G2 phase in human gastric cancer cell lines. The expression of PTEN and
      p27 ( Kip1 ) mRNA was remarkably increased in the gastric cancer cells treated
      with combind drugs (P<0.01). Phosphorylation of Akt, p70S6K and 4E-BP1 were
      significantly reduced in the cells treated with LY294002 or RAPA (P<0.01), but we
      failed to find that 5-aza-dC enhance these effects. We suggested that mTOR
      inhibition could enhance the effects of 5-aza-dC on suppressing cell
      proliferation and arresting cell cycle in human gastric cancer cell lines, which
      might be a potential target for tumor therapy.

PMID- 18622748
TI  - KAI1/CD82 suppresses hepatocyte growth factor-induced migration of hepatoma cells
      via upregulation of Sprouty2.
AB  - We conducted a study concerning the suppressive mechanism of KAI1/CD82 on
      hepatoma cell metastasis. Hepatocyte growth factor (HGF) induces the migration of
      hepatoma cells through activation of cellular sphingosine kinase 1 (SphK1).
      Adenovirus-mediated gene transfer of KAI1 (Ad-KAI1) downregulates the SphK1
      expression and suppresses the HGF-induced migration of SMMC-7721 human
      hepatocellcular carcinoma cells. Overexpression of KAI1/CD82 significantly
      elevates Sprouty2 at the protein level. Ablation of Sprouty2 with RNA
      interference can block the KAI1/CD82-induced suppression of hepatoma cell
      migration and downregulation of SphK1 expression. It is demonstrated that
      KAI1/CD82 suppresses HGF-induced migration of hepatoma cells via upregulation of
      Sprouty2.

PMID- 18622749
TI  - Molecular characterization and expression analysis of caveolin-1 in pig tissues.
AB  - Members of the caveolin family played important roles during fundamental cellular
      processes, such as regulation of cell morphology, migration, and gene expression
      in muscle cells. In this study, caveolin-1 (Cav-1), one of the caveolins, was
      identified from longissimus dorsi muscle of Large Yorkshire pig and Chinese
      indigenous Lantang pig based on the results of mRNA differential display
      analysis. The deduced amino acids sequence of the porcine Cav-1 contained a
      caveolin domain, and was very conservative among different species. The Cav-1
      mRNA was widely expressed in the eight tissues in this study, including heart,
      liver, kidney, encephalon, spleen, lung, longissimus dorsi muscle, and back fat,
      and the highest expression quantity was found in back fat of the two pig breeds.
      The expression quantity of porcine Cav-1 in back fat and longissimus dorsi muscle
      of Lantang pig was significantly higher than that of Large Yorkshire (P<0.01, and
      P<0.05, respectively). These results suggested that the Cav-1 might be a
      candidate gene for carcass traits, and might provide valuable information for
      understanding the mechanism of caveolae signaling in fat deposition by using the
      animal model of pig.

PMID- 18622750
TI  - Evaluation of ecosystem services of Chinese pine forests in China.
AB  - Evaluation of forest ecosystem services is a hot topic, both in China and at
      abroad, but it has not yet obtained a consistency of evaluation indicator systems
      and evaluation methods. Under the framework of evaluation criteria to be
      implemented for forest ecosystem services, years of consecutive observation data
      from Long Term Ecological Research Stations affiliated to Chinese Forest
      Ecosystem Research Network (CFERN), forest resource inventory and public data
      were applied to carry out a detailed and dynamic evaluation on the physical
      quantity and value of ecosystem services of Chinese pine forests in China. The
      results showed that the above services had the total value and unit value of
      1144.9640 billion (1.1449640x10(12)) RMB and 52.074 thousand RMB per hectare per
      year, respectively during the 9th Five-year Plan (1996-2000), and of 1190.5461
      billion RMB and 52.101 thousand RMB per hectare per year, respectively, during
      the 10th Five-year Plan (2001-2005). For Chinese pine forests, water conservation
      was 40.40 hundred million cubic meters annually, soil conservation was 67 million
      tons and C fixation 9 million tons annually, production of healthful negative
      ions was 1.96x10(20), absorption of SO(2) was 5.02 hundred million kilograms and
      dust-catching was 759.10 hundred million kilograms. Among the 15 provinces of
      China with Chinese pine forests, the biggest beneficiary from ecosystem services
      was Liaoning Province; while Hunan Province was the smallest beneficiary between
      the 9th Five-year Plan.

PMID- 18622752
TI  - Engineering and assaying of cytochrome P450 biocatalysts.
AB  - Cytochrome P450s constitute a highly fascinating superfamily of enzymes which
      catalyze a broad range of reactions. They are essential for drug metabolism and
      promise industrial applications in biotechnology and biosensing. The constant
      search for cytochrome P450 enzymes with enhanced catalytic performances has
      generated a large body of research. This review will concentrate on two key
      aspects related to the identification and improvement of cytochrome P450
      biocatalysts, namely the engineering and assaying of these enzymes. To this end,
      recent advances in cytochrome P450 development are reported and commonly used
      screening methods are surveyed.

PMID- 18622751
TI  - Dopaminergic and serotonergic modulation of persistent behaviour in the
      reinforced spatial alternation model of obsessive-compulsive disorder.
AB  - RATIONALE: We have proposed rewarded T-maze alternation as a model of obsessive
      compulsive disorder (OCD): the serotonin agonist m-chlorophenylpiperazine (mCPP)
      increments persistence therein, while chronic pretreatment with selective
      serotonin reuptake inhibitor (SSRI fluoxetine) but not benzodiazepine or
      desipramine abolishes mCPP effects. However, we noted that acute SSRI
      administration also causes transient persistence increase, counteracted by mCPP
      pretreatment. OBJECTIVES: This study (a) further explores the cross-tolerance
      between fluoxetine and mCPP and (b) extends the model by investigating its
      sensitivity to dopaminergic manipulations (D2, 3 agonism--quinpirole). MATERIALS
      AND METHODS: In both experiments, baseline and drug testing were carried out
      under daily T-maze alternation training. Exp. 1: Matched group (n = 8) pairs of
      rats received one of the following 20-day pretreatments (daily intraperitoneal
      administration): (1) saline, (2) low-dose fluoxetine (2.5 mg/kg), (3) low-dose
      mCPP (0.5 mg/kg) or (4) combined fluoxetine + mCPP. One group per pretreatment
      then received a 4-day challenge with high-dose fluoxetine (10 mg/kg), the other
      with high-dose mCPP (2.5 mg/kg). Exp. 2: One group (n = 12) of rats received 20
      day treatment with saline, another with quinpirole (0.5 mg/kg). RESULTS: Exp. 1:
      Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant
      persistence increases under both challenges, while combined low-dose fluoxetine +
      mCPP pretreatment afforded full protection from either challenge. Exp. 2:
      Quinpirole significantly increased directional persistence after 13
      administration days. CONCLUSIONS: These results establish the sensitivity of the
      rewarded alternation OCD model to D2, 3 receptor activation, thereby extending
      its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a
      common mechanism of action of an SSRI and a serotonin agonist in the control of
      directional persistence.

PMID- 18622753
TI  - Fabrication of an iodide-selective electrode based on
      phthalocyaninatotitanium(IV) oxide and the selective determination of iodide in
      actual samples.
AB  - This work describes the development and fabrication of a selective polymeric
      membrane electrode for iodide ion based on a metallophthalocyanin complex with a
      titanium(IV) atom at the center (as an oxo-titanium, Ti=O, group),
      phthalocyaninatotitanium(IV) oxide (PcTiO), as a sensing carrier. The potential
      response characteristics of the electrode were investigated by changing the type
      of plasticizer as well as the amounts of the carrier and different lipophilic
      ionic site additives in the sensing membrane. It is shown that the membrane
      electrode incorporated with 2-nitrophenyl octyl ether as the plasticizer and
      hexadecyl trimethylammonium bromide as the appropriate cationic additive exhibits
      enhanced potential response toward iodide over other anions tested. Over the
      period of this study, the resulting electrode based on PcTiO displayed a stable
      near-Nernstian slope approaching -58.9 mV decade(-1) with a linear response
      spanning at least 5 orders of magnitude in concentration from 1.0 x 10(-1) to 9.2
      x 10(-7) mol L(-1) and a detection limit of 8.5-10(-7) mol L(-1). The
      preferential potential response to iodide may be attributed to the unique
      recognition of carrier PcTiO in the organic membrane phase for iodide in
      solution. Under laboratory conditions, the present electrode also works well in
      partially nonaqueous media. The excellent analytical features of the proposed
      electrode could lead to its successful application in determining the end point
      in electrometric titration of iodide with Ag(+) and the direct potential
      determination of iodide concentration in wastewater and drug preparations.

PMID- 18622754
TI  - GC-MS with ethyl chloroformate derivatization for comprehensive analysis of
      metabolites in serum and its application to human uremia.
AB  - An optimized method based on GC-MS with ethyl chloroformate derivatization has
      been developed for the comprehensive analysis of endogenous metabolites in serum.
      Twenty-two reference standards and serum samples were used to validate the
      proposed method. The correlation coefficient was higher than 0.9900 for each of
      the standards, and the LOD varied from 125 to 300 pg on-column. The analytical
      equipment exhibited good repeatability (RSD<10%) for all of the standards. Both
      the repeatability and the within-48-h stability of the analytical method were
      satisfactory (RSD<10%) for the 18 metabolites identified in the serum samples.
      Mean recovery was acceptable for the 18 metabolites, ranging from 70% to 120%
      with RSDs of less than 10%. Using the optimized protocol and a subsequent
      multivariate statistical technique, complete differentiation was achieved between
      the metabolic profile of uremic patients and that of age- and sex-matched normal
      subjects. Significantly decreased levels of valine, leucine, and isoleucine and
      increased levels of myristic acid and linoleic acid were observed in the patient
      group. This work demonstrated that this method is suitable for serum-based
      metabolic profiling studies.

PMID- 18622755
TI  - A structural constitutive model for the human lens capsule.
AB  - Published data on the mechanical performance of the human lens capsule when
      tested under uniaxial and biaxial conditions are reviewed. It is concluded that
      two simple phenomenological constitutive models (namely a linear elastic model
      and a Fung-type hyperelastic model) are unable to provide satisfactory
      representations of the mechanical behaviour of the capsule for both of these
      loading conditions. The possibility of resolving these difficulties using a
      structural constitutive model for the capsule, of a form that is inspired by the
      network of collagen IV filaments that exist within the lens capsule, is explored.
      The model is implemented within a rectangular periodic cell. Prescribed stretches
      are imposed on the periodic cell and the network is allowed to deform in a non
      affine manner. The performance of the constitutive model correlates well with
      previously published test data. One possible application of the model is in the
      development of a multi-scale analysis of the mechanics of the human lens capsule.

PMID- 18622756
TI  - An alternative method for genotyping of the ACE I/D polymorphism.
AB  - The mistyping of the angiotensin I-converting enzyme insertion/deletion (ACE I/D)
      has been well documented, and new methods have been suggested here to improve the
      genotyping efficiency. Buccal cell samples were collected from 157 young
      Caucasians, and genotyped using previously known and newly developed PCR
      amplification genotyping techniques, as well as PCR-RFLP tests for three single
      nucleotide polymorphisms (rs4327, rs4341 and rs4343). Inconsistent genotyping
      results were found when using only the PCR amplification genotyping techniques
      across repeated attempts (8% to 45%), however, individual SNP genotyping was
      highly consistent (100%). Two SNPs (rs4341 and rs4343) were in complete LD and
      SNP rs4327 was in high LD with the ACE I/D. The ACE I/D was in HW equilibrium in
      the portion of the population with consistent genotyping results, whereas the
      three SNPs were not in HW equilibrium. The mistyping of ACE I/D by only PCR
      amplification can be improved using alternative methods.

PMID- 18622757
TI  - Polymorphism of prion protein gene in Arctic fox (Vulpes lagopus).
AB  - Prion diseases are fatal neurodegenerative disorders of humans and certain other
      mammals. Prion protein gene (Prnp) is associated with susceptibility and species
      barrier to prion diseases. No natural and experimental prion diseases have been
      documented to date in Arctic fox. In the present study, coding region of Prnp
      from 135 Arctic foxes were cloned and screened for polymorphisms. Our results
      indicated that the Arctic fox Prnp open reading frame (ORF) contains 771
      nucleotides encoding 257 amino acids. Four single nucleotide polymorphisms (SNPs)
      (G312C, A337G, C541T, and A723G) were identified. SNPs G312C and A723G produced
      silent mutations, but SNPs A337G and C541T resulted in a M-V change at codon 113
      and R-C at codon 181, respectively. The Arctic fox Prnp amino acid sequence was
      similar to that of the dog (XM 542906). In short, this study provides preliminary
      information about genotypes of Prnp in Arctic fox.

PMID- 18622758
TI  - Identification and characterization of differentially expressed genes in the
      resistance reaction in taro infected with Phytophthora colocasiae.
AB  - Leaf blight disease caused by Phytophthora colocasiae represents a major
      constraint to the growth and yield of taro (Colocasia esculenta L.). Ongoing
      research on model plant systems has revealed that defense responses are activated
      via signaling pathways mediated by endogenous signaling molecule such as
      salicylic acid, jasmonic acid, and ethylene. Activation of plant defenses is
      associated with changes in the expression of large number of genes. To gain a
      better understanding of defense responses, virulent race of P. colocasiae was
      used to inoculate the taro cultivar UL-56 (compatible) and its nearly isogenic
      line Muktakeshi (incompatible). We have employed suppressive subtractive
      hybridization (SSH), cDNA libraries, Northern blot analysis, high throughput DNA
      sequencing, and bioinformatics to identify the defense-related genes in taro
      induced by P. colocasiae infection. Two putative resistance genes and a
      transcription factor were identified among the upregulated sequences. The
      expression of several candidate genes including lipid transfer proteins (LTPs),
      and other pathogenesis-related genes were evaluated following 8-48 h of
      appearance of symptom in compatible and incompatible interactions. Results
      confirmed the higher overall expression of these genes in Muktakeshi (resistant)
      compared to UL-56 (susceptible). This study constitutes the first attempt to
      characterize the taro differential transcriptome associated with host-pathogen
      interactions from different genotypes. All the generated ESTs have been submitted
      to GenBank for further functional studies.

PMID- 18622759
TI  - Identification of a C-type lectin from the bay scallop Argopecten irradians.
AB  - C-type lectins are Ca(2+) dependent carbohydrate-recognition proteins that play
      crucial roles in the invertebrate innate immunity, such as nonself recognition,
      activation of proPO system, antibacterial activity, promotion of phagocytosis and
      nodule formation. In this study, a novel C-type lectin of bay scallops Argopecten
      irradians (Ai Lec) was identified using expressed sequence tag (EST) and RACE
      techniques. The Ai Lec cDNA encoded a polypeptide of 171 amino acids with a
      putative signal peptide of 21 amino acid residues and a mature protein of 150
      amino acids. The deduced amino acid sequence of Ai Lec was highly similar to
      those of the C-type lectins from other animals and contained a typical
      carbohydrate-recognition domain (CRD) of 131 residues, which has four conserved
      disulfide-bonded cysteine residues that define the CRD and two additional
      cysteine residues at the amino terminus. The expression of Ai Lec transcript was
      dominantly detected in the hepatopancreas and slightly detected in the haemocytes
      of normal scallops. 6 h after Vibrio anguillarum-challenge and 8 h after
      Micrococcus luteus-challenge, the temporal expression of Ai Lec mRNA in hemocytes
      was increased by 4.4- and 3.6-folds, respectively. The results suggested that Ai
      Lec was a constitutive and inducible acute-phase protein and might be involved in
      immune response to Gram-negative and Gram-positive microbial infection in bay
      scallop A. irradians.

PMID- 18622760
TI  - Green fluorescent protein is superior to blue fluorescent protein as a
      quantitative reporter of promoter activity in E. coli.
AB  - Fluorescent proteins related to and derived from green fluorescent protein (GFP)
      are widely used as tools for investigating a wide range of biological processes.
      In particular, GFP and its relatives have been used extensively as qualitative
      reporters of gene expression in many different organisms, but relatively few
      studies have investigated fluorescent proteins as quantitative reporters of gene
      expression. GFP has some limitations as a reporter gene, including possible
      toxicity when expressed at high levels. Therefore, it would be useful if other
      fluorescent proteins could be identified for use as quantitative reporters.
      Toward this end, we investigated BFP as a quantitative reporter of promoter
      activity in E. coli and directly compared it with GFPuv using a set of well
      characterized synthetic constitutive promoters. The fluorescence produced in E.
      coli strains expressing GFPuv or BFP grown on solid medium was quantified using a
      CCD camera and fluorimetry. GFPuv consistently gave more reliable and
      statistically significant results than did BFP in all assays. Correspondingly, we
      found that the signal-to-noise ratio for GFPuv fluorescence is substantially
      higher than for BFP. We conclude that, under the conditions assessed in this
      study, GFPuv is superior to BFP as a quantitative reporter of promoter activity
      in E. coli.

PMID- 18622761
TI  - Immunomodulatory effects of phytocompounds characterized by in vivo transgenic
      human GM-CSF promoter activity in skin tissues.
AB  - To investigate the immunomodulatory activities of phytocompounds for potential
      therapeutics, we devised an in vivo, transgenic, human cytokine gene promoter
      assay using defined epidermal skin cells as test tissue. Test compounds were
      topically applied to mouse skin before or after gene gun transfection, using a
      cytokine gene promoter-driven luciferase reporter. Croton oil, an inflammation
      inducer, induced transgenic GM-CSF and TNF-alpha promoter activities in skin
      epidermis 6-fold and 3.4-fold, respectively; however, it produced a less than 1.5
      fold and 1.7-fold change in IL-1beta and IL-18 promoter activity, respectively.
      The phytocompound shikonin drastically inhibited inducible GM-CSF promoter
      activity. However, a fraction of Dioscorea batatas extract significantly
      increased the GM-CSF promoter activity in normal and inflamed skin. Shikonin
      suppressed the transcriptional activity of GM-CSF promoter by inhibiting the
      binding of TFIID protein complex (TBP) to TATA box. Our results demonstrate that
      this in vivo transgenic promoter activity assay system is cytokine gene-specific,
      and highly responsive to pro-inflammatory or anti-inflammatory stimuli. Currently
      it is difficult to profile the expression and cross-talk of various types of
      cytokines in vivo. This investigation has established a bona fide in vivo, in
      situ, immune tissue system for research into cytokine response to inflammation.

PMID- 18622762
TI  - Connective tissue growth factor (CTGF) and cancer progression.
AB  - Connective tissue growth factor (CTGF) is a member of the CCN family of secreted,
      matrix-associated proteins encoded by immediate early genes that play various
      roles in angiogenesis and tumor growth. CCN family proteins share uniform modular
      structure which mediates various cellular functions such as regulation of cell
      division, chemotaxis, apoptosis, adhesion, motility, angiogenesis, neoplastic
      transformation, and ion transport. Recently, CTGF expression has been shown to be
      associated with tumor development and progression. There is growing body of
      evidence that CTGF may regulate cancer cell migration, invasion, angiogenesis,
      and anoikis. In this review, we will highlight the influence of CTGF expression
      on the biological behavior and progression of various cancer cells, as well as
      its regulation on various types of protein signals and their mechanisms.

PMID- 18622763
TI  - Blends of poly(3-hydroxybutyrate) and poly(p-dioxanone): miscibility, thermal
      stability and biocompatibility.
AB  - The miscibility, the thermal degradation and biocompatibility of the blends of
      two biodegradable and bioreabsorbable polymers, brittle polyhydroxybutyric acid
      (PHB) and flexible poly (p-dioxanone) (PPD) are reported. The blends were
      prepared by casting from chloroform solutions and analyzed by differential
      scanning calorimetry, dynamic mechanical analysis, scanning electron microscopy
      and thermal gravimetric analysis. The blends are immiscible and present promising
      morphology of a dense phase and a microporous phase, one or the other being the
      matrix, depending on the composition. Despite the immiscibility, the thermal
      stability under an inert atmosphere is improved for both polymers. The results
      obtained from toxicity tests showed that PHB/PPD blends do not present indirect
      or direct cytotoxicity as a substrate for cellular growth.

PMID- 18622764
TI  - Fabrication of porous titanium scaffold materials by a fugitive filler method.
AB  - A clean powder metallurgy route was developed here to produce Ti foams, using a
      fugitive polymeric filler, polypropylene carbonate (PPC), to create porosities in
      a metal-polymer compact at the pre-processing stage. The as-produced foams were
      studied by scanning electron microscopy (SEM), LECO combustion analyses and X-ray
      diffraction (XRD). Compression tests were performed to assess their mechanical
      properties. The results show that titanium foams with open pores can be
      successfully produced by the method. The compressive strength and modulus of the
      foams decrease with an increasing level of porosity and can be tailored to those
      of the human bones. After alkali treatment and soaking in a simulated body fluid
      (SBF) for 3 days, a thin apatite layer was formed along the Ti foam surfaces,
      which provides favourable bioactive conditions for bone bonding and growth.

PMID- 18622765
TI  - Silk fibroin/chitosan scaffold: preparation, characterization, and culture with
      HepG2 cell.
AB  - Tissue engineering requires the development of three-dimensional water-stable
      scaffolds. In this study, silk fibroin/chitosan (SFCS) scaffold was successfully
      prepared by freeze-drying method. The scaffold is water-stable, only swelling to
      a limited extent depending on its composition. Fourier Transform Infrared (FTIR)
      spectra and X-Ray diffraction curves confirmed the different structure of SFCS
      scaffolds from both chitosan and silk fibroin. The homogeneous porous structure,
      together with nano-scale compatibility of the two naturally derived polymers,
      gives rise to the controllable mechanical properties of SFCS scaffolds. By
      varying the composition, both the compressive modulus and compressive strength of
      SFCS scaffolds can be controlled. The porosity of SFCS scaffolds is above 95%
      when the total concentration of silk fibroin and chitosan is below 6 wt%. The
      pore sizes of the SFCS scaffolds range from 100 microm to 150 microm, which can
      be regulated by changing the total concentration. MTT assay showed that SFCS
      scaffolds can promote the proliferation of HepG2 cells (human hepatoma cell line)
      significantly. All these results make SFCS scaffold a suitable candidate for
      tissue engineering.

PMID- 18622767
TI  - Precipitation of calcium phosphate in the presence of albumin on titanium
      implants with four different possibly bioactive surface preparations. An in vitro
      study.
AB  - The aim of the present study was to compare the nucleating behaviour on four
      types of bioactive surfaces by using the simulated body fluid (SBF) model with
      the presence albumin. Titanium discs were blasted (B) and then prepared by alkali
      and heat treatment (AH), anodic oxidation (AO), fluoridation (F), or
      hydroxyapatite coating (HA). The discs were immersed in SBF with 4.5 mg/ml
      albumin for 3 days, 1, 2, 3 and 4 weeks and analysed with scanning electron
      microscopy/energy dispersive X-ray analysis (SEM/EDX) and X-ray photoelectron
      spectroscopy (XPS). Topographic surface characterisation was performed with a
      contact stylus profilometer. The results demonstrated that the bioactive surfaces
      initiated an enhanced calcium phosphate (CaP) formation and a more rapid increase
      of protein content was present on the bioactive surfaces compared to the blasted
      control surface. The observation was present on all bioactive surfaces. The fact
      that there was a difference between the bioactive surfaces and the blasted
      control surface with respect to precipitation of CaP and protein content on the
      surfaces support the fact that there may be biochemical advantages in vivo by
      using a bioactive surface.

PMID- 18622766
TI  - Periodontal regeneration in experimentally-induced alveolar bone dehiscence by an
      improved porous biphasic calcium phosphate ceramic in beagle dogs.
AB  - Regeneration of lost periodontium is the focus of periodontal therapy. To achieve
      the effective regeneration, a number of bone graft substitute materials have been
      developed. This study aimed to investigate the histological response in alveolar
      bone dehiscences which were filled with an improved biphasic calcium phosphate
      (BCP) ceramic with more reasonable pore diameter, pore wall thickness and
      porosity. Twenty-four alveolar bone dehiscences were made surgically in twelve
      beagle dogs by reflecting mucoperiosteal flaps on the buccal aspect of bilateral
      lower second premolars and removing alveolar bone. The left dehiscences were
      treated with BCP ceramic and the contralaterals were cured with the open flap
      debridement (OFD) as controls. Three dogs were used at week 4, 12, and 24
      respectively. Histological observations were processed through three-dimensional
      micro-computed tomographic imaging, fluorescence and light microscopy. The
      histological study indicated that the biphasic ceramic was biocompatible, and
      regeneration was achieved more effectively through the BCP treatment. There were
      also arrest of epithelial migration apically and formation of new bone and
      cementum, as well as proliferation of fibrous connective tissues that became
      attached to the newly formed cementum at week 24, while there was no significant
      periodontal regeneration in the OFD group only with epithelial tissue migrating
      into the dehiscence regions. Clinically speaking, though the surgical location
      formed a limitation to the application of the improved BCP on the periodontal
      regeneration, the actual result was positive. It proved that the BCP had
      biocompatibility and was able to act as a stable scaffold to induce periodontal
      regeneration effectively.

PMID- 18622768
TI  - Bone-like apatite layer formation on the new resin-modified glass-ionomer cement.
AB  - In this study, the apatite-forming ability of the new resin-modified glass
      ionomer cement was evaluated by soaking the cement in the simulated body fluid.
      The Fourier Transform Infrared (FTIR) spectrometer and X-Ray Diffraction (XRD)
      patterns of the soaked cement pointed to the creation of poorly crystalline
      carbonated apatite. It was found that the releasing of calcium ions from the
      soaked cement will dominate the undesirable effect of polyacrylic acid on apatite
      formation. Consequently, the ionic activity products (IAPs) of the apatite in the
      surrounding medium increased which accelerated apatite nucleation induced by the
      presence of the Si-OH and COOH groups. Accordingly, the apatite nuclei started to
      form via primary heterogeneous nucleation and continued by secondary nucleation.
      Therefore, nucleation and growth occurs as in the layer-by-layer mode so that
      finite numbers of monolayers are produced. Subsequent formation of film occurs by
      formation of discrete nuclei (layer-plus-island or SK growth).

PMID- 18622770
TI  - Life and death of female gametes during oogenesis and folliculogenesis.
AB  - The vertebrate ovary is an extremely dynamic organ in which excessive or
      defective follicles are rapidly and effectively eliminated early in ontogeny and
      thereafter continuously throughout reproductive life. More than 99% of follicles
      disappear, primarily due to apoptosis of granulosa cells, and only a minute
      fraction of the surviving follicles successfully complete the path to ovulation.
      The balance between signals for cell death and survival determines the destiny of
      the follicles. An abnormally high rate of cell death followed by atresia can
      negatively affect fertility and eventually lead irreversibly to premature ovarian
      failure. In this review we provide a short overview of the role of programmed
      cell death in prenatal differentiation of the primordial germ cells and in
      postnatal folliculogenesis. We also discuss the issue of neo-oogenesis. Next, we
      highlight molecules involved in regulation of granulosa cell apoptosis. We
      further discuss the potential use of scores for apoptosis in granulosa cells and
      characteristics of follicular fluid as prognostic markers for predicting the
      outcome of assisted reproduction. Potential therapeutic strategies for combating
      premature ovarian failure are also addressed.

PMID- 18622769
TI  - PEG-grafted chitosan nanoparticles as an injectable carrier for sustained protein
      release.
AB  - The development of injectable nanoparticulate "stealth" carriers for protein
      delivery is a major challenge. The objective of this work was to investigate the
      possibility of achieving the controlled release of a model protein, insulin, from
      PEG-grafted chitosan (PEG-g-chitosan) nanoparticles (mean diameter 150-300 nm)
      prepared by the ion gelation method. Insulin was efficiently incorporated into
      the nanoparticles, and reached as high as 38%. In vitro release showed that it
      could control the insulin release by choosing the composition, loading and
      release temperature. We observed that the composition of the nanoparticle surface
      (C/O ratio) increased from 2.40 to 3.23, with an increase in the incubation time.
      Therefore, we concluded that during this time, insulin release from PEG-g
      chitosan nanoparticles followed a diffusion mechanism in which erosion was
      negligible. The experiments also demonstrated that PEG-g-chitosan helped to
      maintain the natural structure of the protein entrapped in the nanoparticles.

PMID- 18622771
TI  - The role of image guidance in respiratory gated radiotherapy.
AB  - Respiratory gating for radiotherapy beam delivery is a widely available
      technique, manufactured and sold by most of the major radiotherapy machine
      vendors. Respiratory gated beam delivery is intended to limit the irradiation of
      tumours moving with respiration to selected parts of the respiratory cycle, and
      thereby enable dose escalation and/or reduction of dose to organs at risk.
      Without adequate use of respiratory correlated image guidance on a regular basis,
      respiratory beam gating may however have a detrimental effect on target coverage.
      Image guidance of tumour respiratory motion is therefore of utmost importance for
      the safe introduction of respiratory gating. In this short overview, suitable
      image guidance strategies for respiratory gated radiotherapy are reviewed for two
      cancer sites; breast cancer and lung tumours.

PMID- 18622772
TI  - Detection of motor cortex thinning and corticospinal tract involvement by
      quantitative MRI in amyotrophic lateral sclerosis.
AB  - We prospectively investigated pathological modifications in the corticospinal
      tract (CST), by diffusion tensor imaging (DTI) in 14 patients with sporadic
      amyotrophic lateral sclerosis (ALS) and 12 healthy volunteers. We used a
      validated automated method to accurately measure the in vivo thickness of the
      cerebral cortex. We found a reduction of precentral cortical ribbon thickness in
      ALS patients with respect to control subjects. DTI metrics demonstrated
      disorganization of the CST, as characterized by decreased fractional anisotropy
      (FA) and increased Apparent Diffusion Coefficient in ALS patients with respect to
      control subjects. Decreased mean FA values along the CST significantly correlated
      with clinical measures of pyramidal and bulbar impairment. Quantitative analysis
      of MR data shows that thinning of the motor cortex coexists with CST damage in
      ALS patients.

PMID- 18622773
TI  - Symptom subtypes of obsessive-compulsive disorder: are they relevant for
      treatment?
AB  - Several symptom subtypes of obsessive-compulsive disorder (OCD) have been
      identified on the basis of the predominant obsessions and compulsions. The
      objectives of the present article were to review the literature on the
      relationship between OCD symptom subtypes and treatment response and to suggest
      strategies that might assist with the choice of treatment and improve treatment
      outcome in patients with various subtypes. An extensive literature search was
      performed, relevant studies were identified, and their results reported. Overt
      compulsions were generally associated with a relatively good response to the
      behaviour therapy technique of exposure and response prevention (ERP) and with
      poorer response to serotonin re-uptake inhibitors (SRIs). Washing/cleaning and
      checking compulsions tend to respond well to ERP, whereas the majority of studies
      show that washing/cleaning compulsions are associated with a poorer response to
      SRIs. Most studies suggest that patients with the symmetry, ordering and
      arranging subtype do not fare worse with ERP and SRIs than patients with other
      symptom subtypes. Some studies suggested that obsessions might respond to SRIs
      somewhat better than to ERP. In the majority of the studies, hoarding and the
      subtype characterized by sexual or religious obsessions and absence of overt
      compulsions ('pure obsessions') have been associated with poor response to ERP
      and SRIs. It was concluded that treatment strategies cannot be precisely tailored
      to OCD symptom subtypes. Many other factors influence the outcome of treatment
      and need to be considered along with the symptom subtypes when making decisions
      about treatment. While ERP and SRIs remain the mainstay of treatment regardless
      of the symptom subtype, the addition of cognitive therapy techniques and/or
      antipsychotic medications may enhance treatment response in the presence of
      certain features discussed in the article.

PMID- 18622774
TI  - Dual constraints on synapse formation and regression in schizophrenia:
      neuregulin, neuroligin, dysbindin, DISC1, MuSK and agrin.
AB  - During adolescence there is a loss of approximately 30% of the synapses formed in
      the cortex during childhood. Comprehensive studies of the visual cortex show that
      this loss of synapses does not occur as a consequence of less appropriate
      projections being eliminated in favour of more appropriate ones. Rather it seems
      that synapses with low efficacy for transmission are eliminated in favour of
      those with higher efficacy. The loss of low-efficacy synapses is known, on
      theoretical grounds, to enhance the function of neural networks, but large
      synapse losses lead to failure of network function. In the dorsolateral
      prefrontal cortex (DLPC) of those suffering from schizophrenia the number of
      synapses is relatively very low, approximately 60% lower than that observed in
      normal childhood. It is not known if this is due to an additional loss over that
      during normal adolescence or whether it results from a failure to form a normal
      complement of synapses during childhood. The first study of synapse loss in the
      mammalian nervous system was made on the neuromuscular junction at Sydney
      University in 1974. Since then this junction has provided principal insights into
      the molecular basis of synapse formation and regression, so providing a paradigm
      for investigations of these phenomena in the DLPC. For example the molecules
      muscle-specific receptor tyrosine kinase (MuSK), agrin and neuregulin have been
      identified and their critical roles in the formation and maintenance of synapses
      elucidated. Loss of function of MuSK or agrin leads to failure of neuromuscular
      synapse formation as well as a loss of approximately 30% of excitatory synapses
      in the cortex. Similar synapse loss occurs on failure of neuregulin in vitro and
      of neuroligin in vivo. It is suggested that three important questions need to be
      answered: first, over what development period are the synapse numbers in DLPC of
      subjects with schizophrenia lower than normal; second, what are the relative
      importance of MuSK/agrin, neuregulin/ErB and neurexin/neuroligin in synapse
      formation and regression in the DLPC; and third, to what extent have these
      molecules gone awry in schizophrenia.

PMID- 18622775
TI  - Social functioning deficits in young people at risk for schizophrenia.
AB  - OBJECTIVE: Impairment in social functioning is a central feature of schizophrenia
      and is known to be evident before the onset of psychosis, acting as a potential
      vulnerability marker. The aim of the present study was to test the hypothesis
      that social impairment is simultaneously a state and trait marker of risk for
      schizophrenia and schizophrenia-related disorder. METHOD: Social functioning was
      examined in three groups: ultra-high-risk subjects (UHR, n =32), genetic high
      risk subjects (GHR, n =32), and age- and IQ-matched healthy controls (HC, n =30).
      Social functioning was assessed using the Social Functioning Scale (SFS), and
      prodromal symptoms were assessed in high-risk subjects using the Comprehensive
      Assessment of At-Risk Mental States (CAARMS). RESULTS: Both the UHR and GHR
      groups exhibited significantly impaired social functioning compared with the HC
      group, and the UHR group was more impaired than the GHR group. In the UHR group,
      duration of prodromal symptoms was related to impaired 'interpersonal behaviour'.
      Positive and negative symptoms were not significantly associated with social
      functioning, whereas disorganized and general symptoms were significantly
      correlated with poor 'independence-competence' in UHR individuals. CONCLUSION:
      The findings support the hypothesis that impairment in social functioning is both
      a trait and state marker of risk for schizophrenia and other psychotic disorders,
      implying that social impairment constitutes a mediating vulnerability indicator
      of psychotic disorders including schizophrenia.

PMID- 18622776
TI  - Social dysfunction in bipolar disorder: pilot study.
AB  - OBJECTIVE: The purpose of the present study was to assess the social skills of
      euthymic patients with bipolar disorder. METHODS: A group of 25 outpatients with
      bipolar disorder type I were evaluated in comparison with a group of 31 healthy
      volunteers who were matched in terms of level of education, age, sex and
      intelligence. Both groups were assessed using a self-report questionnaire, the
      Brazilian Inventario de Habilidades Sociais (IHS, Social Skills Inventory). Two
      Wechsler Adult Intelligence Scale subtests (Picture Arrangement and
      Comprehension) were also used in order to assess subject ability to analyse
      social situations and to make judgements, respectively. RESULTS: Patients with
      bipolar disorder had lower IHS scores for the domains that assessed
      conversational skills/social self-confidence and social openness to new
      people/situations. Patients with anxiety disorders had high scores for the domain
      that assessed self-confidence in the expression of positive emotions. No
      differences were found between patients and controls in performance on the
      Wechsler Adult Intelligence Scale Picture Arrangement and Comprehension subtests.
      CONCLUSIONS: Euthymic patients with bipolar disorder present inhibited and
      overattentive behaviour in relation to other people and their environment. This
      behaviour might have a negative impact on their level of social functioning and
      quality of life.

PMID- 18622777
TI  - Reducing symptoms of trauma among carers of people with psychosis: pilot study
      examining the impact of writing about caregiving experiences.
AB  - OBJECTIVES: To establish whether writing about experiences of the first episode
      of psychosis may alleviate trauma-like symptoms among carers of people with
      psychosis. METHOD: A total of 37 people caring for someone with early psychosis
      were randomized to two conditions: either writing about the first psychotic
      episode, or writing about time management. Data were collected before and after
      intervention, and 8 weeks later. RESULTS: Those in the writing group were
      significantly less likely to avoid reminders and feelings associated with their
      relative's episode at follow up. Furthermore, carers in this group who exhibited
      trauma-like symptoms had significantly greater reductions in trauma severity.
      CONCLUSIONS: Written emotional disclosure can help carers who are experiencing
      trauma symptoms following a relative's first episode of psychosis. If writing
      about emotional events is beneficial through mechanisms of exposure then
      screening participants for trauma symptoms may eliminate previous research
      inconsistencies. These results, however, need to be replicated in a larger study.

PMID- 18622778
TI  - Cognitive and health-related outcomes of group cognitive behavioural treatment
      for people with depressive symptoms in Hong Kong: randomized wait-list control
      study.
AB  - OBJECTIVES: This study examined the efficacy of a territory-wide cognitive
      behavioural group treatment programme for Chinese people with depression launched
      in Hong Kong. METHOD: Three hundred and forty-seven subjects with depressive
      symptoms (i.e. Beck Depression Inventory-Chinese version >9) were randomly
      assigned to CBT and waitlist control groups. RESULTS: After 10 weeks of
      treatment, participants in the group CBT programme had significantly fewer
      symptoms of depression, fewer dysfunctional and perfectionist attitudes, and
      better quality of life when compared to the participants in the control group.
      Effect size statistics showed small to medium differences in symptoms of
      depression, dysfunctional and perfectionist attitudes and quality of life between
      the two groups (Cohen's d, 0.22-0.74). Statistical analysis of the clinical
      significance indicated that approximately 27% of the participants in the
      experimental group could be considered as clinically remitted or recovered,
      respectively (RCI >1.28). Last, multiple regression provided some evidence of a
      linkage between cognition and depression among the participants in the
      experimental group. CONCLUSIONS: The design and content of the group CBT
      programme, which aimed at facilitating the understanding and modification of
      automatic thoughts and dysfunctional attitudes among the participants, might have
      contributed to the initial positive results.

PMID- 18622779
TI  - Pilot evaluation of parent-child interaction therapy delivered in an Australian
      community early childhood clinic setting.
AB  - OBJECTIVE: Parent-child interaction therapy (PCIT) is a short-term, evidence
      based parent training intervention used widely in the treatment of behaviourally
      disordered preschool-aged children. Outcome studies have shown PCIT to be
      associated with lasting improvements in child and sibling behaviours and in the
      interactional styles, stress levels, confidence, and psychological functioning of
      parents. To date, however, all outcome studies have been conducted in university
      research clinic settings, and therefore understanding about the effectiveness of
      PCIT applied in a real-world setting has been limited. The present study
      evaluated the effectiveness of PCIT delivered to families in an Australian
      community-based early childhood clinic. METHOD: Participants included 43 families
      with children aged 19-52 months who were referred for treatment of disruptive
      child behaviours and who completed PCIT treatment at the Karitane Toddler Clinic,
      in Sydney, Australia. Parents provided pre- and post-treatment ratings of child
      behaviours, parental stress, parental psychopathology and parental attitudes to
      therapy. RESULTS: At the end of the programme, clinically and statistically
      significant improvements were seen in child behaviours and parental well-being,
      and parents reported high levels of satisfaction with treatment. CONCLUSIONS:
      Implications for the implementation of PCIT programmes in community-based
      settings are discussed and areas of further research are identified.

PMID- 18622780
TI  - Early childhood predictors of early substance use and substance use disorders:
      prospective study.
AB  - OBJECTIVES: The purpose of the present study was to examine the longitudinal
      association between early childhood factors and early initiation of use of
      substances and substance use disorders in a large prospective study. METHOD: Data
      were from the Mater Hospital University of Queensland Study of Pregnancy, a
      prospective birth cohort study in Brisbane, Australia. Use of nicotine, alcohol
      and cannabis and age of initiation of such use were reported at the 21 year
      follow up. DSM-IV diagnosis of nicotine, alcohol and cannabis use disorders was
      assessed at 21 years using a computerized version of the Composite International
      Diagnostic Interview (CIDI-Auto). Early childhood factors were measured between
      mother's pregnancy and child age 5 years. RESULTS: Of the 3647 respondents with
      complete data, 15.4% had started to smoke cigarettes before 15 years. Another
      17.4% and 12.2% reported having started to consume alcohol or use cannabis in
      early adolescence, respectively. Some 16.2%, 27.8% and 21.9% had ever had
      nicotine, alcohol or cannabis abuse or dependence (disorder) by 21 years,
      respectively. In multivariate models early initiation of use of substances, and
      substance use disorders were associated with disrupted families or drug-using
      parents, childhood problem behaviours, and poor parental monitoring and
      supervision in childhood. CONCLUSIONS: There are four independent factors in
      early or middle childhood that predict early initiation of use of substances and
      subsequent substance use disorders by early adulthood. There is a need to
      consider whether what is known about the risk factors that predict young age of
      substance use, and substance use disorders, may be incorporated into treatment
      and/or prevention initiatives.

PMID- 18622781
TI  - Use of community treatment orders to prevent psychiatric hospitalization.
AB  - OBJECTIVE: The purpose of the present study was to analyse how, for whom, under
      what circumstances, and with what consequences for a patient's treatment career
      the community treatment orders (CTOs) were used to prevent psychiatric
      hospitalization during the course of a decade in Victoria, Australia. METHOD:
      Records were obtained from the Victorian Psychiatric Case Register for 8579
      patients who were exposed to CTOs. Descriptive statistics and logistic regression
      were used to determine the characteristics of patients solely selected for
      placement on orders directly from the community, in lieu of hospitalization,
      versus patients selected for placement on orders only from the hospital or for
      those who experienced both hospital- and community-initiated orders. Ordinary
      least squares regression was used to evaluate the relationship of sole reliance
      on community-initiated orders and experienced changes in future hospital
      utilization. RESULTS: CTOs were infrequently issued directly from the community
      by comparison with outpatient orders issued at termination of inpatient episodes.
      Patients whose placements on orders were carried out only through direct
      community placement differed from those whose placement was primarily initiated
      from hospital or from both hospital and community. The former group, although
      largely consisting of people with schizophrenia, was less likely to include such
      patients than the comparison samples. It also included fewer male subjects and
      'never married' individuals as well as more individuals with major affective
      disorders. Those served solely with community-initiated orders had significantly
      less use of subsequent inpatient care than individuals in the comparison samples,
      all other diagnostic and pre-morbid adjustment characteristics taken into
      account. CONCLUSION: For patients at risk of beginning a career of long-term
      psychiatric hospitalization, sole reliance on community-initiated orders appeared
      to prevent additional hospital involvement. The issuance of orders from hospital
      and the combined-order strategy were associated with protective oversight
      throughout extended inpatient careers. Sole reliance on community-initiated
      outpatient orders provided a 'least restrictive' alternative to hospitalization.

PMID- 18622782
TI  - Regulator of G-protein signalling 4 expression is not altered in the prefrontal
      cortex in schizophrenia.
AB  - OBJECTIVES: Regulator of G-protein signalling 4 (RGS4) modulates signal
      transduction through several neurotransmitter receptor systems associated with
      the pathology of schizophrenia. A reported decrease in RGS4 expression in the
      prefrontal cortex of schizophrenia patients followed by supporting evidence from
      association studies implicated RGS4 as a susceptibility gene for schizophrenia.
      Subsequent efforts to extend these findings in post-mortem brain tissue have
      produced conflicting results. The aim of the present study was to reconcile these
      discrepancies by examining RGS4 expression in the dorsolateral prefrontal and
      parietal cortices from subjects with schizophrenia. METHODS: RGS4 mRNA and
      protein levels were measured in post-mortem Brodmann area (BA)9 and BA40 tissue
      from 19 schizophrenia patients subjects and 19 pair-matched controls using in
      situ hybridization and western blotting. RESULTS: Levels of RGS4 mRNA
      (F(1,73)=1.845; p >0.05) or protein (F(1,72)=3.336 x 10(-4), p >0.05) did not
      vary significantly with diagnosis in BA9 or BA40 from subjects with
      schizophrenia. CONCLUSIONS: Altered RGS4 expression is not universally present
      throughout the cortex of people with schizophrenia.

PMID- 18622783
TI  - Bupropion-induced hypomania in a patient with unipolar depression.

PMID- 18622786
TI  - Thought suppression and persecutory delusion-like beliefs in a nonclinical
      sample.
AB  - INTRODUCTION: Thought suppression may play a role in the formation and/or
      maintenance of persecutory delusions, although this possibility has not yet been
      empirically studied. We investigated thought suppression levels in relation to
      the presence of persecutory delusion-like beliefs (PDLBs), and hypothesised that
      only when levels of anxiety or negative affect were high would thought
      suppression predict levels of PDLBs. METHOD: Thought suppression, anxiety,
      negative affect, social desirability, and persecutory ideation were assessed in a
      nonclinical sample (N=183) using online questionnaires. RESULTS: When gender,
      anxiety, and negative affect were controlled, the interaction between thought
      suppression and anxiety predicted levels of PDLBs. Further analysis of this
      interaction showed that thought suppression was positively associated with PDLBs
      only when anxiety was high. Neither thought suppression by itself, nor the two
      way interaction between negative affect and thought suppression, nor the three
      way interaction between negative affect, anxiety, and thought suppression, were
      predictors of PDLB levels. CONCLUSION: The results are consistent with a proposed
      interaction between thought suppression and anxiety in the development of PDLBs.
      Possible causal mechanisms underlying this relation are considered further,
      future research in the area proposed, and potential clinical implications
      examined.

PMID- 18622787
TI  - An orbitofrontostriatopallidal pathway for morality: evidence from postlesion
      antisocial and obsessive-compulsive disorder.
AB  - INTRODUCTION: A detailed proposal is made to the effect that nonlesional
      antisocial personality disorder (APD) is, among other things, a dysfunctional
      hypomoralism and that nonlesional obsessive-compulsive disorder (OCD) is, among
      other things, a dysfunctional hypermoralism. METHOD: To provide an empirical test
      of this proposal, 25 previously published cases of acquired (post lesion) APD and
      39 cases of acquired OCD are reviewed and compared with multivariate inference
      tests. RESULTS: The acquired APD patients most often present putamenal or
      pallidal lesions. CONCLUSION: The ensemble of neurobiological, endocrine, and
      behavioural traits in APD and OCD, as well as the distinct lesion sites in the
      acquired variants, support the notion of an orbitofrontostriatopallidal brain
      system underlying morality.

PMID- 18622788
TI  - Hypersociability in Williams syndrome: a role for the amygdala?
AB  - We read with great interest the paper of Riby et al. regarding atypical,
      unfamiliar face processing in Williams syndrome (WS; Riby, Doherty-Sneddon, &
      Bruce, 2008a). It offers considerable insight into the mechanism of facial
      perception in humans and a further elaboration of the hypersociability observed
      in patients with Williams syndrome. We would like to suggest that the neurologic
      mechanisms underlying the hypersociability in WS may be attributable to an
      impaired recognition of facial expressions of threat, a feature that localises to
      the amygdala.

PMID- 18622789
TI  - Emotion word use in the conversational speech of schizophrenia patients.
AB  - INTRODUCTION: Many recent studies have found that, although schizophrenia
      patients tend to display diminished facial expressions of emotion, they report
      levels of emotional experiences that are similar to those of controls. Although
      these findings are very informative, it is unknown whether such dissociation
      exits for other modalities such as verbal expression of emotion. The purpose of
      this study was to investigate the association between the use of emotion words
      during a free speech task and subjective experience of emotion in schizophrenia
      patients and controls. METHODS: Speech samples of 48 schizophrenia patients and
      48 nonpsychiatric control individuals were compared on the type and amount of
      emotional words used, as well as on the level of self-reported stress experienced
      while providing descriptions of themselves. RESULTS: Groups did not differ in the
      amount or type of emotion words uttered during the free speech task. Patients,
      however, found the task more stressful than controls. Emotion word use and
      subjective emotional experience were not related in either group. CONCLUSIONS:
      Results do not fully support prior findings, but are consistent with the notion
      of a lack of correspondence between the expression and experience of emotion.

PMID- 18622790
TI  - Working memory and depressive symptoms in patients with schizophrenia and
      substance use disorders.
AB  - BACKGROUND: Substance abuse is highly prevalent in schizophrenia and it has been
      associated with negative consequences on the course of the pathology. Regarding
      cognition, the prevailing literature has produced mixed results. Some groups have
      reported greater cognitive impairments in dual diagnosis schizophrenia, while
      other groups have described the reverse. OBJECTIVE: The current cross-sectional
      study sought to investigate the potential differences in psychiatric symptoms and
      cognition between schizophrenia patients with and without substance use
      disorders. METHODS: Fifty-three schizophrenia patients were divided into two
      groups: with (n=30) and without (n=23) a substance use disorder (DSM-IV
      criteria). Psychiatric symptoms were measured with the Positive and Negative
      Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS).
      Psychomotor speed and spatial working memory were measured using Cambridge
      Neuropsychological Tests Automated Battery (CANTAB). RESULTS: Patients in the
      dual diagnosis group displayed more severe depressive symptoms and poorer
      strategy during the working memory task. CONCLUSIONS: These results are in
      keeping with the prevailing literature describing negative consequences of
      substance abuse in schizophrenia. Substance abuse may exacerbate depressive
      symptoms and interfere with metacognition in schizophrenia.

PMID- 18622792
TI  - Navigated revision knee arthroplasty using a system designed for primary surgery.
AB  - While navigation is now recognized as an efficient tool for improving femoro
      tibial alignment of primary knee prostheses, its use in revision surgery has not
      yet been fully evaluated. We describe a procedure based on a bone morphing
      acquisition performed on the surface of the original implants, followed by a
      dependant bone cut sequence (tibia first). Using the current system, a
      preoperative CT-scan measurement of the original femoral component was required.
      Knee balancing was achieved using spacer blocks, with the trial tibial component
      and the original femoral component still in place. Preliminary experience from 19
      cases, some with severe bone loss requiring reconstruction, is reported. A
      retrospective comparison to 10 non-navigated revision cases performed
      concomitantly by the same operating surgeon was carried out. Although there was
      no significant difference in the number of outliers for the two series,
      navigation appeared to be a valuable aid in reconstructing both bone extremities,
      while controlling the level of the joint line. However, definitive validation
      requires further prospective and comparative investigations in larger series.

PMID- 18622793
TI  - Accuracy assessment of CT-based outer surface femur meshes.
AB  - OBJECTIVES: Computer-aided bone surgery planning and implant design applications
      require accurate and compact representations of the patient's bone. The accuracy
      of bone segmentation from medical images has been studied extensively, with each
      study using a specific ground truth and a specific type and number of accuracy
      measurements. However, for convenience and practical reasons these three
      specifications have always been limited. The goal of this study is to thoroughly
      assess the absolute 3D accuracy of CT-based bone outer surface meshes, using
      femora as the examples. MATERIALS AND METHODS: Using dense and very accurate
      optical surface scans of 15 dried femora as an absolute ground truth, this paper
      reports on the absolute 3D geometric accuracy of triangulated bone outer surface
      meshes, which were segmented from the CT scans of the corresponding formalin
      fixed intact cadaver specimens using the author's previously presented contour
      based segmentation algorithm on the one hand, and the commercially available
      Mimics(R) software (Materialise N.V., Leuven, Belgium) on the other. The study
      incorporates the effect of soft tissue presence on hard tissue segmentation and
      simultaneously reveals the accuracy shift introduced as a result of boiling the
      cadaver bones by processing extra CT scans of the dried bones. RESULTS: The
      presented study demonstrates that, when using the optimal parameter settings for
      the respective segmentation procedures, sub-voxel mesh accuracies can be
      attained. Compact surface representations of femora can be generated with mean
      absolute accuracies of up to one fifth of the voxel size and Root Mean Square
      (RMS) error of half the voxel size. CONCLUSIONS: The 3D accuracy of the contour
      based segmentation previously presented by the author makes it most suitable for
      generating outer bone surface meshes for use in the aforementioned applications.
      The optimal parameter settings for this segmentation procedure have been
      identified. For the Mimics bone surface meshes, a single, but excellent, pre
      defined set of parameters was identified.

PMID- 18622794
TI  - Transepicondylar axis accuracy in computer assisted knee surgery: a comparison of
      the CT-based measured axis versus the CAS-determined axis.
AB  - Rotational malalignment is recognized as one of the major reasons for knee pain
      after total knee arthroplasty (TKA). Although Computer Assisted Orthopaedic
      Surgery (CAOS) systems have been developed to enable more accurate and consistent
      alignment of implants, it is still unknown whether they significantly improve the
      accuracy of femoral rotational alignment as compared to conventional techniques.
      We evaluated the accuracy of the intraoperatively determined transepicondylar
      axis (TEA) with that obtained from postoperative CT-based measurement in 20
      navigated TKA procedures. The intraoperatively determined axis was marked with
      tantalum (RSA) markers. Two observers measured the posterior condylar angle (PCA)
      on postoperative CT scans. The PCA measured using the intraoperatively determined
      axis showed an inter-observer correlation of 0.93. The intra-observer
      correlation, 0.96, was slightly better than when using the CT-based angle. The
      PCA had a range of -6 degrees (internal rotation) to 8 degrees (external
      rotation) with a mean of 3.6 degrees for observer 1 (SD = 4.02 degrees ) and 2.8
      degrees for observer 2 (SD = 3.42 degrees ). The maximum difference between the
      two observers was 4 degrees . All knees had a patellar component inserted with
      good patellar tracking and no anterior knee pain. The mean postoperative flexion
      was 113 degrees (SD = 12.9 degrees ). The mean difference between the two
      epicondylar line angles was 3.1 degrees (SD = 5.37 degrees ), with the CT-based
      PCA being larger. During CT-free navigation in TKA, a systematic error of 3
      degrees arose when determining the TEA. It is emphasized that the intraoperative
      epicondylar axis is different from the actual CT-based epicondylar axis.

PMID- 18622795
TI  - A feasibility study of computer-assisted bone graft implantation for tissue
      engineered replacement of the human ankle joint.
AB  - OBJECTIVE: Computer-assisted graft implantation may contribute to achieving
      biological joint replacement in the future. The purpose of this experimental
      study was to evaluate the feasibility and accuracy of a series of computer
      assisted graft implantations into human cadaver ankle joints. METHODS: Three
      dimensional graft models of virtually planned corresponding tibial and talar
      defects were created from bovine cancellous bone. A platform for computer
      assisted surgery (CAS) was set up to implant the grafts. Registration was
      performed by pair-point matching with anatomical landmarks. In the case of
      insufficient registration accuracy, artificial landmarks were used for
      registration. Eight grafts (four tibial, four talar) were implanted in four human
      cadaver ankle joints. Postoperative CT was used for outcome analysis. The
      following criteria of accuracy were defined: macroscopic quality of implant fit;
      quality of the sagittal and coronar joint surface; and quality of the
      undersurface of the graft in relation to the base of the defect. RESULTS: No
      technical complications were observed during computer-assisted graft
      implantation. Clinically acceptable accuracy was achieved in 6 of 8 graft
      implantations, with implant failure occurring at the tibial and talar location in
      one ankle joint. In total, 25 of 32 criteria of accuracy were achieved: 6/8 for
      macroscopic implant fit; 5/8 for quality of the sagittal joint surface; 7/8 for
      quality of the coronar joint surface; and 7/8 for quality of the undersurface of
      the graft. Registration with anatomical landmarks did not achieve sufficient
      accuracy in 4 of 8 cases, whereas registration with artificial landmarks was
      successful in all these cases. CONCLUSIONS: We demonstrated the feasibility and
      accuracy of computer-assisted graft implantation for tissue-engineered
      replacement of the human ankle joint. However, we cannot recommend the present
      type of registration by pair-point matching with anatomical landmarks due to the
      considerable inaccuracies. The focus should be on the improvement of non-invasive
      registration techniques and methods for evaluating postoperative outcome.

PMID- 18622796
TI  - Soft tissue dissection in placement of reference markers during computer aided
      total hip arthroplasty.
AB  - OBJECTIVE: During computer navigated hip arthroplasty, impingement of soft
      tissues on reference markers (RMs) may cause errors in the navigation process.
      The aim of this study was to investigate the effect of such soft tissue
      impingement during limb movement on the stability of different RMs. MATERIALS AND
      METHODS: The stability of one- and two-screw RM systems inserted using three
      different levels of soft tissue dissection was analyzed in fresh cadaver lower
      limbs. All tests were done with RMs inserted in both the distal-anterior femur
      and the distal-lateral femur. RESULTS: Rotations of less than 0.15 degrees and
      translations of less than 0.4 mm occurred in most test combinations. The
      combination that showed the greatest instability was when a stab incision was
      used to insert a screw in the distal-lateral femur (translation: 0.73 +/- 0.05
      mm; rotation: 0.25 +/- 0.05 degrees ) (p < 0.001). This instability occurred in
      both single- and double-screw RMs (p = 0.21). CONCLUSIONS: Reference markers can
      be placed in the anterior distal femur through stab incisions without resulting
      in significant impingement during limb movement. When RMs are placed in the
      lateral distal femur, impingement may occur from the fascia lata. Release of the
      fascia lata 1 cm either side of the screw prevents significant impingement. Wide
      skin incision is unnecessary in any location.

PMID- 18622797
TI  - Comparison of operative time and accuracy using conventional fixed navigation
      cutting blocks and adjustable Pivotal cutting blocks.
AB  - Computer-assisted navigation in total knee arthroplasty has been shown to improve
      implant positioning and may lead to improved patient outcomes. The purpose of
      this study was to assess differences in time and accuracy using a navigation
      system with either a conventional (20 knees) or specially designed (20 knees)
      system of cutting blocks. The time needed for fixing and positioning the
      specially designed blocks averaged 2.9 minutes, compared to 6.4 minutes for the
      conventional blocks (p < 0.001). In the coronal plane, the mean angular
      difference between the instrument slot and the resected bone was smaller for the
      specially designed blocks than for the conventional blocks. This difference was
      significant for both the femoral (p = 0.007) and tibial (p = 0.028) cuts. These
      encouraging results show the need for further study of navigation in total knee
      arthroplasty.

PMID- 18622798
TI  - The influence of metal artifacts on navigation and the reduction of artifacts by
      the use of polyether-ether-ketone.
AB  - Registration is a crucial step in navigation assisted surgery. When performing
      anatomical pair-point registration, there are several potential sources of error,
      including inadequate data acquisition, improper segmentation, and distortion
      resulting from metal artifacts. The aim of this study was to evaluate the
      influence of metal artifacts on the precision of Iso-C(3D) and fluoroscopy-based
      navigation, and to assess any changes in precision from the use of a newly
      developed Schanz screw composed of polyether-ether-ketone (PEEK OPTIMA). A T
      shaped test specimen was manufactured from synthetic bone material. It was then
      scanned with a Siremobil Iso-C(3D) while different types of implant were present
      in the specimen. Five Iso-C(3D) scans were acquired: one with a steel Schanz
      screw in the specimen, one with a titanium screw, one with a PEEK screw, one with
      a 5-hole plate, and one with no screw or plate present. The registration was
      analyzed by "reverse verification" with a pointer in a purpose-built, manipulable
      3D holder. All experiments were then repeated using fluoroscopy-based navigation.
      Increasing presence of metal in the scan area resulted in an increase in mean
      error (0.55 mm with the steel Schanz screw, 0.7 mm with the 5-hole plate).
      Artifacts resulting from the titanium Schanz screw were less than those caused by
      the stainless steel Schanz screw. While this study demonstrates that metallic
      artifacts do have an influence on the precision of Iso-C(3D) navigation, such
      artifacts were not found to be a factor when performing fluoroscopy-based
      navigation.

PMID- 18622799
TI  - Lymphocyte recovery: an overlooked contribution to autologous stem cell
      transplant outcome.

PMID- 18622800
TI  - Development of a cyclodextrin-based nasal delivery system for lorazepam.
AB  - A new drug delivery system containing hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) and a mucoadhesive polymer was developed with the aim to overcome the
      limitations connected with the nasal application of drugs with low water
      solubility. Lorazepam, free or as cyclodextrin inclusion complex, was loaded into
      mucoadhesive microparticles by spray drying, using hydroxypropylmethyl cellulose
      (HPMC), carbomer, and HPMC/carbomer interpolymer complex (IPC) as mucoadhesive
      components. Differential scanning calorimetry (DSC) indicated the presence of
      drug crystalline areas in microparticles loaded with free lorazepam, whereas in
      those loaded with HP-beta-CD inclusion complex, the drug was amorphous. Zeta
      potential measurement revealed that the polymer was the main component on the
      surface of the microparticles. The swelling rate and mucoadhesive properties of
      the microparticles were determined by the polymer type used in formulation. IPC-
      and carbomer-based microparticles showed superior swelling rate and mucoadhesion
      compared with the HPMC-based microparticles (p < .05). Drug loading into the
      polymer matrix decreased the swelling rate as well as the mucoadhesive properties
      of microparticles (p < .05), whereas the presence of HP-beta-CD in the matrix did
      not induce any additional reduction of those parameters (p > .05). The in vitro
      dissolution studies demonstrated that the microparticles containing the lorazepam
      inclusion complex displayed 1.8-2.5 times faster drug release compared with those
      containing free lorazepam. The change in the drug release rate could be connected
      with improved drug solubility inside the polymer matrix due to inclusion complex
      formation, as well as to the reduction in crystallinity following complexation,
      as confirmed by DSC studies.

PMID- 18622801
TI  - Indoleamine 2,3-dioxygenase activity associates with cardiovascular risk factors:
      the Health 2000 study.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an important immunomodulator suppressing the
      activation of T lymphocytes, and its level in blood is increased in several
      autoimmune and inflammatory diseases. We have previously shown that this activity
      associates with several signs and risk factors of atherosclerosis in 24 to 39
      year-old females. Now we repeat this analysis in an older population (n = 921,
      age range 46-76 years), i.e. in a population with more advanced atherosclerosis.
      IDO activity had a significant positive correlation in both sexes with carotid
      artery intima/media thickness (IMT), an early marker of atherosclerosis. In
      females, a significant negative correlation with HDL cholesterol and a positive
      correlation with triglycerides levels was observed. The association with IMT did
      not remain significant after adjustment with classical risk factors of
      atherosclerosis. It is thus concluded that IDO is a sensitive marker of
      atherosclerosis--or the inflammatory response associated with it--but does not
      have an independent role in the pathogenesis of this disease.

PMID- 18622802
TI  - Substantial discrepancies in 17beta-oestradiol concentrations obtained with three
      different commercial direct radioimmunoassay kits in rat sera.
AB  - The extensive use of oestrogen for contraception and amelioration of post
      menopausal symptoms has made it the subject of substantial recent research
      efforts, and ovariectomized (ovx) rats treated with exogenous ovarial hormones
      are important when investigating the effects and mechanisms of oestrogen actions.
      The crucial need to control and monitor plasma levels of 17beta-oestradiol calls
      for accurate, precise and robust assay methods. The performance of direct
      radioimmunoassays (RIAs) in measurement of 17beta-oestradiol has been reported
      previously for human samples, but to our knowledge not for rat samples. In the
      current study, 552 serum samples from ovx, native and hormone-treated rats were
      used to compare the performance of three commercially manufactured direct RIAs
      from the companies DPC (Siemens Healthcare Diagnostics Inc., formerly Diagnostic
      Products Corporation), DSL (Diagnostic Systems Labs) and MPB (MP Biomedicals,
      formerly ICN Biomedicals). Substantial differences in results between the three
      assay methods were found when measuring serum 17beta-oestradiol concentrations.
      The following formulas describing the relation between the different methods were
      obtained using weighted Deming's orthogonal regression (based on pg/mL): DSL =
      0.43*DPC+12.3, MPB = 2.1*DPC+84.7 and DSL = 4.8*MPB+22.2. Furthermore, a
      preceding diethyl ether extraction step of the serum appears to impair the
      performance of the RIAs in the present samples (based on pg/mL): DPC(ex) =
      0.39*DPC(unex)+0.76, DSL(ex) = 0.32*DSL(unex)-1.7 and MPB(ex) =
      0.22*MPB(unex)+1.4.

PMID- 18622803
TI  - Reproductive history, lifestyle factors and season as determinants for serum
      calcium concentrations in women.
AB  - OBJECTIVE: Serum calcium concentrations have been associated with the risk of
      malignant disease, especially breast cancer. Thus, determinants of serum calcium
      concentrations, with special regard to risk factors of breast cancer, are of
      great interest. MATERIAL AND METHODS: Previous studies have either been small or
      they have not focused on reproductive factors. The present study examined serum
      calcium concentrations in relation to reproductive history, selected lifestyle
      factors and screening season in a large population-based cohort study comprising
      8,114 women. ANOVA followed by the Bonferroni t-test were used for comparison of
      means, and logistic regression and multiple regression analysis were used to test
      associations. RESULTS: Serum calcium concentrations were lower in hormone
      replacement therapy users versus non-users (2.321 mmol/L versus 2.364; p<0.001)
      and in users of oral contraceptives versus non-users (2.304 versus 2.348;
      p<0.001). They were higher in peri-/postmenopausal versus premenopausal women
      (2.357 versus 2.319; p<0.001). Overweight and obese women had higher mean calcium
      concentrations (2.350 and 2.355) than women with body mass index between 20 and
      25 (2.342; p<0.001). Serum calcium concentrations were higher in spring and
      autumn than in winter (2.352 and 2.353 versus 2.343; p = 0.002). Both younger (40
      45 years) (2.334; p = 0.001) and older age groups (>55 years) (2.363; p<0.001)
      had higher mean calcium concentrations compared to those of women aged 45-50
      years (2.320), even when adjusting for menopausal status, suggesting that age has
      an independent influence on calcium concentrations. CONCLUSIONS: It is concluded
      that reproductive factors such as menopausal status, use of oral contraceptives
      or hormone-replacement therapy, and age, BMI and season are associated with serum
      calcium concentrations.

PMID- 18622804
TI  - Psychoneurotic symptoms and alexithymia in coeliac disease.
AB  - OBJECTIVE: Depression, psychological problems and the impairment of quality of
      life are reported to occur in untreated coeliac disease. Alexithymia ("no words
      for feelings") is associated with various gastrointestinal disorders. The aim of
      this study was to evaluate whether patients with coeliac disease suffer from
      psychoneurotic symptoms or alexithymia, and whether a gluten-free diet has an
      impact on the symptoms. MATERIAL AND METHODS: The Crown-Crisp Experiential Index
      (CCEI) and its six subscales were applied to measure neurotic psychopathology,
      and the 20-item version of the Toronto Alexithymia Scale (TAS-20) and its 3
      factor scales to measure alexithymia. The testing was carried out in 20
      consecutive adult patients with biopsy-proven coeliac disease before and after
      one year of treatment on a gluten-free diet. The data were compared with those
      obtained earlier in non-coeliac Finnish subjects. RESULTS: Somatic anxiety was
      higher in coeliac disease patients before the introduction of the gluten-free
      diet than after adhering to the diet. Otherwise, the diet had no significant
      impact on the CCEI scores. The patients were not suffering from alexithymia, but
      the TAS-20 score improved significantly during the follow-up. The scores did not
      differ from those published in the Finnish population. CONCLUSIONS: Psychological
      problems were not common in adult coeliac disease patients. Gluten-free diet had
      only a minor influence on the symptoms. Common knowledge about coeliac disease
      and the readily available gluten-free products may have had an impact on these
      results.

PMID- 18622805
TI  - Infections following damage control laparotomy with abdominal packing.
AB  - Our objective was to describe postoperative infections for patients undergoing
      damage control laparotomy (DCL) with abdominal packing. We retrospectively
      reviewed data on packing patients in Jinling hospital (China) during a 5-y
      period. Of 26 patients, 15 (57.7%) had postoperative infections. Pneumonia/lower
      respiratory tract infection (57.7%), bacteraemia (50%), and urinary tract
      infection (15.4%) were the 3 prominent types of infections. The most frequently
      isolated bacteria were Pseudomonas aeruginosa (20.7%), staphylococcal species
      (15.6%), Acinetobacter baumannii (13.9%), and Klebsiella species (11.1%).
      Antibiotic resistance was common both for the Gram-positive and Gram-negative
      isolates. No statistical correlation was demonstrated between positive packs and
      postoperative infection (p=0.10) or death (p=1.00). Multivariate regression
      analysis revealed pre-existing abdominal infection (OR=22.4, p=0.02) and
      increased number of surgical procedures (OR=3.69, p=0.05) to be independent risk
      factors for postoperative de novo infection. We conclude that patients undergoing
      DCL with packing carry a high incidence of postoperative infections. Causative
      pathogens are typical for ICU acquired infections and are often associated with
      low levels of susceptibility to multiple antimicrobial agents. Pre-existing
      abdominal infection and increased number of surgical procedures are the
      independent risk factors for postoperative de novo infection in these patients.

PMID- 18622806
TI  - Acute childhood bacterial meningitis in Luanda, Angola.
AB  - Incidence, morbidity and mortality of bacterial meningitis in developing
      countries are manifold greater than those in the industrialized world. We
      reviewed retrospectively children with meningitis treated in the paediatric
      hospital of Luanda in 2004. Among the 555 children, median age 11.0 months, the
      leading agents were Haemophilus influenzae type b (Hib), pneumococcus, and
      meningococcus in 60%, 24%, and 10%, respectively. The median length of illness
      before admission was 7 d. 65% had convulsed. Altered level of consciousness was
      observed in 61% and blood haemoglobin lower than 8 g/dl in 36% of cases. Case
      fatality was 35% and, of survivors, 24% were left with severe neurological
      sequelae. Blood transfusion appeared beneficial since fatality of children with
      and without transfusion was 23% versus 39% (p=0.003). While awaiting large-scale
      vaccinations, tools to improve the prognosis of meningitis in Angola comprise
      generating better awareness to reduce the delay, better fluid treatment and
      monitoring and active use of blood transfusions.

PMID- 18622807
TI  - Clinical and technical aspects of bipolar transurethral prostate resection.
AB  - This review aims to provide an overview and critical assessment of the
      developments in transurethral electroresection in non-conductive and conductive
      irrigants. In the 1970s, measurements of the electric pathway in saline were
      performed for different locations of the neutral electrode. It was then concluded
      that the current pathway and the possible hazards of burn injuries to the patient
      should be investigated separately for each arrangement of the neutral electrode.
      The position and shape of the neutral electrode have decisive effects on the
      current flow in the patient. Thus, different electrode arrangements of the
      various bipolar resection systems need to be analysed separately. Furthermore,
      not only electrical power, but also conductivity and quality of the lubricant gel
      have to be considered as critical factors with regard to electrothermal injuries
      of the urethra. The supposedly better cutting quality seems to be based more on
      subjective observations than on scientific valid data. When performing "bipolar"
      TUR it is necessary to consider all electrotechnical and clinical aspects,
      particularly with regard to the potential risk of thermoelectrical urethral
      damage.

PMID- 18622809
TI  - Effect of click trains on duration estimates by people with Parkinson's disease.
AB  - Patients with a diagnosis of Parkinson's disease and age- and IQ-matched controls
      estimated the duration of short 500-Hz tones (325-1,225 ms), on trials where the
      tone was either preceded by 3 s of 5-Hz clicks, or presented without clicks. The
      click manipulation had been shown in earlier studies with student participants to
      make verbal estimates longer. Patients were tested both on and off their
      dopaminergic medication, and controls were also tested in two sessions. Verbal
      estimates were markedly and significantly longer on trials with clicks than on
      those without clicks for both the patients and the controls, but there were no
      significant performance differences between patients or controls, nor between the
      on and off medication sessions in the patients. The study shows that a
      manipulation of subjective time, which has had small but consistent effects in
      student participants, also affects timing in patients and adds to a growing body
      of evidence that timing in patients with Parkinson's disease may in many cases
      have the same characteristics as those of neurologically intact control groups.

PMID- 18622808
TI  - Optimal data partitioning and a test case for ray-finned fishes (Actinopterygii)
      based on ten nuclear loci.
AB  - Data partitioning, the combined phylogenetic analysis of homogeneous blocks of
      data, is a common strategy used to accommodate heterogeneities in complex
      multilocus data sets. Variation in evolutionary rates and substitution patterns
      among sites are typically addressed by partitioning data by gene, codon position,
      or both. Excessive partitioning of the data, however, could lead to
      overparameterization; therefore, it seems critical to define the minimum numbers
      of partitions necessary to improve the overall fit of the model. We propose a new
      method, based on cluster analysis, to find an optimal partitioning strategy for
      multilocus protein-coding data sets. A heuristic exploration of alternative
      partitioning schemes, based on Bayesian and maximum likelihood (ML) criteria, is
      shown here to produce an optimal number of partitions. We tested this method
      using sequence data of 10 nuclear genes collected from 52 ray-finned fish
      (Actinopterygii) and four tetrapods. The concatenated sequences included 7995
      nucleotide sites maximally split into 30 partitions defined a priori based on
      gene and codon position. Our results show that a model based on only 10
      partitions defined by cluster analysis performed better than partitioning by both
      gene and codon position. Alternative data partitioning schemes also are shown to
      affect the topologies resulting from phylogenetic analysis, especially when
      Bayesian methods are used, suggesting that overpartitioning may be of major
      concern. The phylogenetic relationships among the major clades of ray-finned fish
      were assessed using the best data-partitioning schemes under ML and Bayesian
      methods. Some significant results include the monophyly of "Holostei" (Amia and
      Lepisosteus), the sister-group relationships between (1) esociforms and
      salmoniforms and (2) osmeriforms and stomiiforms, the polyphyly of Perciformes,
      and a close relationship of cichlids and atherinomorphs.

PMID- 18622811
TI  - Circadian rhythms of C-FOS expression in the suprachiasmatic nuclei of the common
      vole (Microtus arvalis).
AB  - The suprachiasmatic nuclei of the hypothalamus (SCN) are the master circadian
      clock in mammals. Transcriptional activity in this master clock has a marker in
      the immediate-early gene c-Fos. Within the SCN, distinct differences in c-Fos in
      the ventrolateral and the dorsomedial SCN have been reported for rodent species
      such as rats, mice, and hamsters. We studied C-FOS expression in the common vole
      (Microtus arvalis) SCN under LD 12:12 h and under constant dim light conditions.
      In the vole dorsomedial SCN, rhythmic C-FOS expression was seen in LD with a
      clear peak in the middle of the light period. Under constant dim light, we report
      constitutive, non-rhythmic expression of C-FOS in the dorsomedial SCN. This
      pattern is consistent with the circadian organization of behavioral activity,
      which is weak in voles and may be lost under constant dim-light conditions. In
      the ventrolateral SCN, we observed a rise in C-FOS expression under LD conditions
      prior to lights-on, followed by peak expression at lights-on. Another peak was
      seen at lights-off. In an additional experiment, we subjected animals to LD 16:8
      to test the hypothesis that the dawn and dusk peaks in ventrolateral C-FOS
      expression change phase along with the photoperiod. The peak in C-FOS expression
      did not shift with the time of lights on, but remained at the same external time
      6. The results are consistent with the interpretation that in the vole, c-Fos
      expression reports transcriptional activity associated more likely with an
      internal, gating process than with an external effect of light.

PMID- 18622812
TI  - Effect of NO synthase inhibition on cardiovascular circadian rhythms in wild-type
      and eNOS-knock-out mice.
AB  - Cardiovascular functions (blood pressure [BP], heart rate [HR]) were
      radiotelemetrically studied in endothelial nitric oxide synthase (NOS) knock-out
      mice (eNOS-/-) and their wild type C57BL/6 (WT) controls. Studies were performed
      with and without inhibition of the NOS with the non-specific inhibitor N(omega)
      Nitro-L-Arginin-Methylester (L-NAME). Six eNOS-/-and five WT mice, kept under a
      light:dark schedule of 12:12 h (lights on 07:00 h), were treated with L-NAME in
      tap water containing different concentrations (94, 282, and 940 mg/kg) each for
      three days. Under control conditions, the eNOS-/-mice are mildly hypertensive in
      comparison to WT. L-NAME increased systolic [SBP] and diastolic [DBP] blood
      pressures in WT mice to the levels of eNOS-/-mice after two days of L-NAME
      application with no dose-dependency, whereas L-NAME had no effects on SBP and DBP
      in eNOS-/-mice. In neither mouse strain were the circadian rhythms in BP and HR
      affected by drug treatment. The similarity of the 24 h BP profiles in eNOS-/-and
      L-NAME-treated WT mice support the notion that only the enothelial NOS and not
      other NOS isoenzymes are of importance for hypertension in the knock-out mouse
      strain.

PMID- 18622810
TI  - Executive and attention functioning among children in the PANDAS subgroup.
AB  - Evidence from past studies indicates that adults and children with Obsessive
      Compulsive Disorder (OCD) and Tourette syndrome (TS) experience subtle
      neuropsychological deficits. Less is known about neuropsychological functioning
      of children and adolescents with a symptom course consistent with the PANDAS
      (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal
      infection) subgroup of OCD and tics. To provide such information, we administered
      three tests of attention control and two of executive function to 67 children and
      adolescents (ages 5-16) diagnosed with OCD and/or tics and a symptom course
      consistent with the PANDAS subgroup and 98 healthy volunteers (HV) matched by
      age, sex, and IQ. In a paired comparison of the two groups, the PANDAS subjects
      were less accurate than HV in a test of response suppression. Further, in a two
      step linear regression analysis of the PANDAS group in which clinical variables
      were added stepwise into the model and in the second step matching variables
      (age, sex, and IQ) were added, IQ emerged as a predictor of performance on this
      task. In the same analysis, ADHD diagnosis and age emerged as predictors of
      response time in a continuous performance task. Subdividing the PANDAS group by
      primary psychiatric diagnosis revealed that subjects with TS or OCD with tics
      exhibited a longer response time compared to controls than subjects with OCD
      only, replicating previous findings within TS and OCD. This study demonstrates
      that children with PANDAS exhibit neuropsychological profiles similar to those of
      their primary psychiatric diagnosis.

PMID- 18622813
TI  - Variation of the locomotor activity rhythms in three species of Talitrid
      amphipods, Talitrus saltator, Orchestia montagui, and O. gammarellus, from
      various habitats.
AB  - The expression of biological rhythms was investigated in five populations of
      three different species of talitrid amphipods from various habitats in the
      Maremma Regional Park, Grosseto, Italy: Talitrus saltator (from a sandy beach and
      a canal), Orchestia montagui (form a Posidonia banquette), and O. gammarellus
      (from a cave entrance and a river bank). Locomotor activity rhythms were recorded
      in individual animals over 21 days in constant dark at a temperature of 18
      degrees +/-1 degrees C. A high variability in rhythm expression was evident, not
      only among species and populations but also within populations and the activity
      pattern of individuals. Activity rhythms of T. saltator and O. montagui were
      similar, with a good definition and precise circadian periodicity, whereas O.
      gammarellus showed a high variability and low definition of the circadian rhythm.
      Significant differences were also observed between two populations of O.
      gammarellus and T. saltator from different habitats. Within the O. gammarellus
      species, a significantly higher percentage of active animals (p<0.001) was
      observed in the cave than the river-bank population; within T. saltator, a
      significantly lower percentage of active animals (p<0.01) and higher percentage
      of periodic animals (p<0.05) was found in the canal than the sandy beach
      population. With reference to environmental stability and variability, the
      differences observed are explained as a need for plasticity to adapt to
      environmental changes.

PMID- 18622814
TI  - Circadian time-effect of orally administered loratadine on plasma
      pharmacokinetics in mice.
AB  - Little is known about the chronopharmacokinetics of loratadine, a long-acting
      tricyclic antihistamine H(1) widely used in the treatment of allergic diseases.
      Hence, the pharmacokinetics of loratadine and its major metabolite,
      desloratadine, were investigated after a 20 mg/kg dose of loratadine had been
      orally administered to comparable groups of mice (n=33), synchronized for three
      weeks to 12 h light (rest span)/12 h dark (activity span). The drug was
      administered at three different circadian times (1, 9, and 17 h after light onset
      [HALO]). Multiple blood samples were collected over 48 h, and plasma
      concentrations of loratadine and desloratadine were determined by high
      performance liquid chromatography. There were no significant differences in
      T(max) of loratadine and desloratadine between treatment-time different groups.
      However, the elimination half-life (t1/2) of the parent compound and its
      metabolite was significantly longer (p<0.01) following administration at 9 HALO
      (t1/2 loratadine and desloratadine 5.62 and 4.08 h at 9 HALO vs. 4.29 and 2.6 h
      at 17 HALO vs. 3.26 and 3.27 at 1 HALO). There were relevant (p<0.05) differences
      in C(max) between the three treated groups for loratadine and desloratadine;
      133.05+/-3.55 and 258.07+/-14.45 ng/mL at 9 HALO vs. 104.5+/-2.61 and 188.62+/
      7.20 ng/mL at 1 HALO vs. 94.33+/-20 and 187.75+/-10.79 ng/mL at 17 HALO. Drug
      dosing at 17 HALO resulted in highest loratadine and desloratadine total apparent
      clearance values: 61.46 and 15.97 L/h/kg, respectively, whereas loratadine and
      desloratadine clearances (CL) were significantly slower (p<0.05) at the other
      administration times (loratadine and desloratadine CL was 57.3 and 14.22 L/h/kg
      at 1 HALO vs. 43.79 and 12.89 L/h/kg at 9 HALO, respectively). The area under the
      concentration-time curve (AUC) of loratadine and desloratadine was significantly
      (p<0.05) greater following drug administration at 9 HALO (456.75 and 1550.57
      (ng/mL) . h, respectively); it was lowest following treatment at 17 HALO (325.39
      and 1252.53 (ng/mL) . h, respectively). These pharmacokinetic data indicate that
      the administration time of loratadine significantly affected its
      pharmacokinetics: the elimination of loratadine and its major metabolite
      desloratadine.

PMID- 18622816
TI  - Differences in sleep and circadian preference between Eastern and Western German
      adolescents.
AB  - Only a few studies focus on comparisons to reveal differences in sleep and
      circadian preferences in adolescents. This study used the same instrument to
      compare adolescents in Eastern and Western Germany. In all, 674 pupils between 11
      and 16 yrs participated. The questionnaire asked questions about wake times and
      bed times (on weekend and weekdays), and the Composite Scale of Morningness (CSM)
      was completed to assess diurnal preferences. Locality (East/West Germany) had no
      effect on rise and bed times during the week and on sleep length on the weekend.
      Western pupils rose later on weekends and went to bed later on weekends. While
      sleep length on weekdays was shorter in West Germany, weekend oversleep was
      longer and misalignment was higher. Diurnal preferences (CSM scores) suggested a
      higher eveningness in West Germany. As interaction effects were insignificant,
      changes throughout adolescence seem similar in East and West Germany. These data
      suggest that given similar school start times, Western German pupils are at
      higher risk because they are later chronotypes. The finding of earlier rise and
      bed times of the East German pupils is consistent with the hypothesis that
      sunlight acts as the entrainment for the biological clock of adolescents, as
      sunrise is earlier in Eastern Germany.

PMID- 18622815
TI  - A study of the association between sleep habits and problematic behaviors in
      preschool children.
AB  - This preliminary study examined the association between sleep habits and
      problematic behaviors in healthy preschool children using an internationally
      standardized method. Two groups of 4-6-yr-old healthy Japanese children were
      recruited. Children in Group A (n=68) met one or more of the following three
      conditions: they went out from their home with adults after 21:00 h two or more
      times a week, they went to bed after 23:00 h four or more times a week, and they
      returned home after 21:00 h three or more times a week, while those in Group B
      (n=67) met none of these conditions. Sleep-wake logs and the Child Behavior
      Checklist (CBCL)/4-18 were completed daily for two weeks. The CBCL consists of
      questions with 113 items categorized into eight subscale items: (I) Withdrawn,
      (II) Somatic complaints, (III) Anxious/depressed, (IV) Social problems, (V)
      Thought problems, (VI) Attention problems, (VII) Delinquent behavior, and (VIII)
      Aggressive behavior. Internalizing (I+II+III), externalizing (VII+VIII), and
      total scale scores were also derived. Generally, the higher the score, the
      greater the likelihood of problematic behaviors in that scale. We compared both
      the CBCL scores and distribution of the CBCL score-determined clinical
      classification of behavior (normal, borderline, and abnormal) between the groups.
      Correlation coefficients between CBCL scores and each of the seven indices of the
      studied sleep habits (wake-up times, bedtimes, nocturnal sleep duration, nap
      duration, total sleep duration, and range of variation in wake-up and bedtime)
      were also assessed. Group A children showed significantly shorter average
      nocturnal sleep, nap, and total sleep duration, significantly later average
      bedtimes and wake-up times, and a significantly greater range of variation in
      bedtimes and wake-up times than Group B children. The CBCL score of the total
      scale was significantly higher in Group A than Group B children. The distribution
      of the clinical classifications of behavior between the two groups showed no
      significant differences. Although nocturnal sleep, nap, and total sleep duration
      did not correlate with total CBCL score, it showed a high positive correlation
      with wake-up times, bedtimes, and ranges of variation in both wake-up and bed
      times. The distribution of the clinical classification for the total scale showed
      significant differences between early and late risers, and also between regular
      and irregular sleepers. The number of children classified as normal for the total
      scale score was higher in early risers and regular sleepers than in late risers
      and irregular sleepers. Preschool children of Group A, late risers, late
      sleepers, irregular risers, and irregular sleepers were likely to show
      problematic behaviors.

PMID- 18622817
TI  - Diurnal variation in energetic arousal, tense arousal, and hedonic tone in
      extreme morning and evening types.
AB  - The aim of the present study was to examine levels of energetic arousal (EA),
      tense arousal (TA), and hedonic tone (HT) in individuals with different circadian
      preferences. Subjects were males with extreme either morning (M-type) or evening
      (E-type) preferences (N=31), selected using the Morningness-Eveningness
      Questionnaire cutoff points derived from the Polish population norms. They
      completed the UWIST Mood Adjective Check List every 1.5 h between 08:00 to 20:00
      h in laboratory conditions. The obtained data showed higher levels of TA and
      lower levels of HT in E-types over the whole day as compared to M-types. As for
      EA, M-types showed higher levels than E-types between 08:00 to 17:00 h, but the
      two groups showed no differences during the later hours of the day. Both groups
      were found to exhibit similar diurnal patterns in TA and HT, and dissimilarity
      between M-types and E-types appeared in the daily course of EA. The results show
      the three-dimensional model of mood is more advantageous in M-types than in E
      types during the hours of typical human activity.

PMID- 18622818
TI  - Differential 24-hour variation of alertness and subjective tension in process
      controllers: investigation of the relationship with body temperature and heart
      rate.
AB  - The effects of shift and time-on-shift on alertness and perceived tension, as
      well as related physiological variables, were investigated in satellite
      controllers working a rapid forward rotating three-shift system. In controlled
      laboratory conditions, subjective tension and HR have been reported to display
      circadian variation and marked sensitivity to external factors. We examined
      whether circadian variations were masked for these particular variables in real
      job conditions, unlike for alertness and body temperature, which have been
      repeatedly shown to display circadian variation in these conditions. This
      hypothesis was tested in a repeated-measures design by collecting alertness and
      tension self-reports and recording operators' sublingual temperature on three
      occasions on each shift and HR continuously throughout shifts. Alertness and body
      temperature varied according to a typical diurnal trend; subjective tension was
      only enhanced on the initial recording of each shift (compared to the remaining
      ones), while HR displayed an intermediary trend. Intra-subject correlations
      revealed a positive relationship between alertness, oral temperature, and HR,
      while no such relationship was found for subjective tension. These results
      support the hypothesis of a close dependence of alertness and temperature, and to
      a lesser extent for HR, on endogenous mechanisms in this job-situation. In
      addition, some situation-specific factors, such as job-demand, would affect
      subjective tension and partially mask the circadian variations in HR.

PMID- 18622819
TI  - Regularity of daily activities in stroke.
AB  - Various studies have been performed using the Social Rhythm Metric (SRM), though
      none has been developed with stroke patients. Stroke is a pathology that provokes
      a strong physical and social impact caused by an abnormality in cerebral
      circulation. Consequently, we performed two studies to validate the SRM and
      translate it into Portuguese, and to evaluate the regularity of the daily
      activities of stroke patients. Both healthy individuals and patients with
      unilateral cerebral lesions were evaluated. Subjects were of both sexes and
      between 45 and 65 yrs of age. Participants underwent clinical evaluation and
      recorded the time of 17 daily activities on the SRM for two weeks. Data were
      analyzed by the Pearson correlation and Fisher tests. After conceptual
      translation into Portuguese, corrections were made to arrive at the final
      version. Normative SRM scores varied from 3.2 to 7.0, suggesting that the
      activities presented in SRM adequately represented the daily routines of the
      patients. A correlation was found in SRM between the weeks (r=0.84; p=0.0001),
      indicating instrument reliability. The mean (+/-SD) score of the stoke patients
      was 4.8 (+/-1.0), and the correlation between the SRM and level of neurological
      damage showed that patients with lower SRM values were more physically
      compromised (r=-0.29; p=0.04), suggesting that SRM may be a clinical predictor.
      Activities related to eating and the sleep-wake cycle were rated by most
      patients. In all, 71% of the patients did not work, while 84% of healthy
      individuals did (p=0.001). Only 64% of patients left home compared to 90% of the
      healthy subjects (p=0.001), and 59% of patients recorded the activity of going
      home compared to 82% of healthy individuals (p=0.001). According to the results,
      there is evidence of the validity and reliability of the SRM, enabling it to be
      reliably used in chronobiological studies of stroke patients. Given that a less
      regular lifestyle may be associated with neurological compromise and a decrease
      in social activities, we suggest new studies with the repeated application of
      this instrument over the clinical evolution of the disease to better define
      improvement or worsening of the patient's condition in terms of their social and
      health aspects.

PMID- 18622820
TI  - Internal desynchronization of circadian rhythms and tolerance to shift work.
AB  - Intolerance to shift work may result from individual susceptibility to an
      internal desynchronization. Some shift workers (SW) who show desynchronization of
      their circadian rhythms (e.g., sleep-wake, body temperature, and grip strength of
      both hands) exhibit symptoms of SW intolerance, such as sleep alteration,
      persistent fatigue, sleep medication dependence, and mood disturbances, including
      depression. Existing time series data previously collected from 48 male Caucasian
      French SW were reanalyzed specifically to test the hypothesis that internal
      synchronization of circadian rhythms is associated with SW intolerance and
      symptoms. The entry of the subjects into the study was randomized. Three groups
      were formed thereafter: SW with good tolerance (n=14); SW with poor tolerance, as
      evident by medical complaints for at least one year (n=19); and former SW (n=15)
      with very poor tolerance and who had been discharged from night work for at 1.5
      yr span but who were symptom-free at the time of the study. Individual and
      longitudinal time series of selected variables (self-recorded sleep-wake data
      using a sleep log, self-measured grip strength of both hands using a Colin
      Gentile dynamometer, and oral temperature using a clinical thermometer) were
      gathered for at least 15 days, including during one or two night shifts.
      Measurements were performed 4-5 times/24 h. Power spectra used to quantify the
      prominent period (tau) and t-test, chi square, and correlation coefficient were
      used as statistical tools. The mean (+/-SEM) age of SW with good tolerance was
      greater than that of SW with poor tolerance (44.9+/-2.1 yrs vs. 40.1+/-2.6 yrs,
      p<.001) and of former SW discharged from night work (very poor tolerance; 33.4+/
      1.7, p<.001). The shift-work duration (yrs) was longer in SW with good than poor
      tolerance (19.9+/-2.2 yrs vs. 15.7+/-2.2; p<0.002) and former SW (10.7+/-1.2;
      p<.0001). The correlation between subject age and shift-work duration was
      stronger in tolerant SW (r=0.97, p<.0001) than in non-tolerant SW (r=0.80,
      p<0.001) and greater than that of former SW (r=0.72, p<.01). The mean sleep-wake
      rhythm tau was 24 h for all 48 subjects. The number of desynchronized circadian
      rhythms (tau differing from 24 h) was greater in non-tolerant than in tolerant SW
      (chi square=38.9, p<.0001). In Former SW (i.e., 15 individuals assessed in follow
      up studies done 1.5 to 20 yrs after return to day work), both symptoms of
      intolerance and internal desynchronization were reduced or absent. The results
      suggest that non-tolerant SW are particularly sensitive to the internal
      desynchronization of their circadian time organization.

PMID- 18622821
TI  - Melatonin binding sites in senegal sole: day/night changes in density and
      location in different regions of the brain.
AB  - We localized melatonin binding sites in different brain regions (optic tectum,
      telencephalon, cerebellum, hypothalamus, olfactory bulbs, and medulla oblongata)
      of Senegal sole, a species of aquaculture interest, and checked day/night changes
      in density (B(max)) at mid-light (ZT06) and mid-dark (ZT18). Plasma melatonin was
      measured using a radioimmunoassay, while binding assays were performed using 2
      [(125)I]iodomelatonin as a radioligand. Plasma melatonin concentrations were
      significantly lower at mid-light (189.5+/-46 pg/ml) than mid-dark (455.5+/-163
      pg/ml). Values of B(max) were statistically significantly higher in the optic
      tectum (5.6+/-0.6 and 12.3+/-1 fmol/mg prot, at mid-light and mid-dark,
      respectively) and in the cerebellum (7.7+/-1.1 and 10.6+/-1.3 fmol/mg prot, at
      mid-light and mid-dark, respectively). Significant day/night differences were
      only observed in these two tissues. These results show for the first time the
      distribution of melatonin binding sites within the brain of a flatfish species
      and their lack of down-regulation.

PMID- 18622822
TI  - On melatonin suppression from polychromatic and narrowband light.

PMID- 18622823
TI  - The effects of a 1-year physical exercise programme on development of fatigue
      during a simulated ambulance work task.
AB  - The aim of the study was to evaluate the effects of individually prescribed
      physical exercise programmes on development of fatigue during the carrying of a
      loaded stretcher up and down the stairs. Nineteen ambulance personnel performed
      the training for 1 year. Testing occurred before and after 1 year of the
      training. Both the training group (n = 19) and the control group (n = 15) were
      assessed for physical capacity and lactate concentration in blood and ratings of
      perceived exertion during carrying a stretcher on the stairs. When comparisons
      were made between those who had been training three times/week for 1 year and the
      control group, lactate concentration was significantly decreased. In conclusion,
      markers of fatigue during stretcher carrying can be reduced by the use of
      individually prescribed physical exercise programmes.

PMID- 18622824
TI  - The Cochran-Weiss-Shanteau performance index as an indicator of upper limb risk
      assessment expertise.
AB  - Ergonomists and many other professionals apply ergonomics principles to
      musculoskeletal health problems. This study examines whether there are
      differences when it comes to judgement expertise concerning upper limb disorders
      (ULDs) between ergonomists and those with less ergonomics training. The Cochran
      Weiss-Shanteau (CWS) performance index combines judgement consistency with
      discrimination into one CWS index. Fifty-eight professionals working in the
      musculoskeletal health area, from four different professions, judged the
      likelihood of staff complaining of ULDs in a number of written work scenarios
      containing ULD risk factors. A student group (n = 148) taking an introductory
      ergonomics module was used as a reference. The ergonomists scored higher on the
      CWS index than all of the other groups, performing significantly better than all
      but the occupational health advisors. Performance improved with increased
      training level but not with experience. This study suggests that ergonomists are
      quantifiably different from other ergonomics advisors in their judgement
      performance in this context. Given the global cost of musculoskeletal disorders,
      assessing the expertise of those giving ergonomics advice for the management of
      musculoskeletal health is of great significance. This study presents a method for
      assessing judgement performance in ULD risk assessment, an important part of
      musculoskeletal health management.

PMID- 18622828
TI  - Fracture behaviour of zirconia ceramic cantilever fixed dental prostheses in
      vitro.
AB  - OBJECTIVE: Evaluation of the fracture resistance of all-ceramic cantilever fixed
      dental prostheses (FDPs) manufactured from zirconia frameworks and veneered with
      a press ceramic. MATERIAL AND METHODS: Two mandibular premolars were prepared
      either with a box inlay cavity or with a full crown chamfer preparation and then
      duplicated. 40-three-unit cantilever FDPs replacing one premolar, with a group
      size of eight for each design, were manufactured. In group i-i the cantilever
      FDPs were retained by two inlays, in group i-c by an inlay-crown combination, and
      in group c-c by two crowns. The frameworks in groups i-c-R and c-c-R were
      reinforced by an additional shoulder on the oral side of the zirconia frameworks.
      All FDPs were subjected to thermal cycling (TC) and 600,000 cycles of mechanical
      loading (ML) with 50 N. The load to fracture was measured and fracture sites were
      evaluated. RESULTS: The mean fracture values ranged from 172 N to 792 N. Fracture
      strength values were significantly lower for the i-i retained FDPs than for the i
      c and c-c combinations. There was no significant effect of the reinforcing
      shoulder in groups i-c-R and c-c-R. For FDPs with a crown on the terminal tooth,
      fractures were usually within the distal wall of the distal crown. CONCLUSIONS:
      Inlay-inlay retained cantilever FDPs cannot withstand the mastication forces
      expected. Fracture load values for inlay-crown and crown-crown-retained FDPs
      encourage further clinical investigation. The mode of fracture indicates that
      reinforcement of the distal crown wall might enhance fracture resistance.

PMID- 18622829
TI  - Tooth display and lip position during spontaneous and posed smiling in adults.
AB  - OBJECTIVE: To analyze differences in tooth display, lip-line height, and smile
      width between the posed smiling record, traditionally produced for orthodontic
      diagnosis, and the spontaneous (Duchenne) smile of joy. MATERIAL AND METHODS: The
      faces of 122 male participants were each filmed during spontaneous and posed
      smiling. Spontaneous smiles were elicited through the participants watching a
      comical movie. Maxillary and mandibular lip-line heights, tooth display, and
      smile width were measured using a digital videographic method for smile analysis.
      Paired sample t-tests were used to compare measurements of posed and spontaneous
      smiling. RESULTS: Maxillary lip-line heights during spontaneous smiling were
      significantly higher than during posed smiling. Compared to spontaneous smiling,
      tooth display in the (pre)molar area during posed smiling decreased by up to 30%,
      along with a significant reduction of smile width. During posed smiling, also
      mandibular lip-line heights changed and the teeth were more covered by the lower
      lip than during spontaneous smiling. CONCLUSIONS: Reduced lip-line heights, tooth
      display, and smile width on a posed smiling record can have implications for the
      diagnostics of lip-line height, smile arc, buccal corridors, and plane of
      occlusion. Spontaneous smiling records next to posed smiling records are
      therefore recommended for diagnostic purposes. Because of the dynamic nature of
      spontaneous smiling, it is proposed to switch to dynamic video recording of the
      smile.

PMID- 18622830
TI  - Impact of toothpaste slurry abrasivity and toothbrush filament stiffness on
      abrasion of eroded enamel - an in vitro study.
AB  - OBJECTIVE: Toothbrush abrasion is significant in the development of tooth wear,
      particularly when combined with erosion. This in vitro study aimed to evaluate
      the impact of toothpaste slurry abrasivity and toothbrush filament stiffness on
      abrasion of eroded enamel. MATERIAL AND METHODS: Eroded enamel samples
      (hydrochloric acid, pH: 2.6, 15 s) were brushed with 40 strokes in an automatic
      brushing machine using manual toothbrushes with different filament stiffness
      (filament diameter: 0.15, 0.20, or 0.25 mm). A paste-free control slurry
      (relative enamel abrasion (REA) value 2) and toothpaste slurries with different
      abrasivity (REA values 6 or 9) were used for brushing. Erosion and abrasion were
      followed by storing the enamel samples in artificial saliva for 3 h. After each
      4th cycle, the samples were stored in artificial saliva for 15 h. After 60
      cycles, enamel loss was measured by profilometry and statistically analyzed by
      two-way and one-way ANOVA and Bonferroni/Dunn post-hoc tests. RESULTS: Loss of
      enamel (mean, microm) was influenced mainly by the abrasivity of the slurry and
      increased along with REA value (REA 2: 0.0-0.2, REA 6: 2.1-3.3, REA 9: 2.9-3.7).
      Abrasion of eroded enamel was also affected by filament stiffness of the
      toothbrush, but only groups brushed with toothpaste slurry of REA 6 showed any
      significant difference between the different toothbrushes. Thereby, toothbrushes
      with 0.2 mm filament diameter caused higher enamel loss than 0.15 and 0.25 mm
      filaments. CONCLUSIONS: Toothbrush abrasion of eroded enamel is influenced mainly
      by the abrasivity of the toothpaste slurry, but is also modified by toothbrush
      filament stiffness.

PMID- 18622831
TI  - Effect of the cross-linking silane concentration in a novel silane system on
      bonding resin-composite cement.
AB  - OBJECTIVE: Four experimental blends of an organo-functional silane monomer with a
      non-functional cross-linking silane monomer (a novel silane system) were
      evaluated as adhesion promoters in an experiment in which a resin-composite
      cement was bonded to silica-coated titanium. MATERIAL AND METHODS: 3
      Acryloyloxypropyltrimethoxysilane (as constant 1.0 vol%) was blended with 1,2-bis
      (triethoxysilyl)ethane, where its concentration was 0.1, 0.2, 0.3, or 0.5 vol%.
      Titanium slides (n=20) were grit-blasted, silica-coated, and silanized with four
      experimental silane solutions, with a pre-activated silane Cimaratrade mark
      (VOCO, Germany) as control. After silanization, resin-composite cement stubs
      (Bifixtrade mark QM; VOCO, Germany) were photo-polymerized. The shear bond
      strength was measured after dry storage (24 h) or after thermo-cycling (6000
      cycles between 5 degrees C and 55 degrees C). The resin stub failure mode was
      determined. RESULTS: Statistical analysis (ANOVA) showed that type of storage (p
      <0.05) and concentration of cross-linker silane (p<0.005) both significantly
      affected the shear bond strength. The highest shear bond strength was obtained
      with a blend of 1.0 vol% 3-acryloyloxypropyltrimethoxysilane+0.3 vol% 1,2-bis
      (triethoxysilyl)ethane, 15.9 MPa (standard deviation SD 3.4 MPa) for both the
      thermo-cycled group and after dry storage (24 h), 14.3 MPa (SD 4.1 MPa)
      (n=8/group). The lowest values were obtained with Cimaratrade mark silane 7.3 MPa
      (SD 2.2 MPa) in dry storage and 7.9 MPa (SD 2.0 MPa) obtained with 1.0 vol% 3
      acryloyloxypropyltrimethoxysilane+0.1 vol% 1,2-bis-(triethoxysilyl)ethane. The
      failure type was mainly cohesive. CONCLUSION: A novel silane system with an
      optimal concentration of the cross-linking silane may produce significantly
      higher shear bond strength between silica-coated titanium and resin-composite
      cement compared to a pre-activated silane product.

PMID- 18622832
TI  - Neonatal hip instability, developmental dysplasia of the acetabulum, and the risk
      of early osteoarthrosis.

PMID- 18622833
TI  - Diagnosis of congenital hip dysplasia in the newborn.
AB  - BACKGROUND AND PURPOSE: Screening of newborn infants for congenital hip dysplasia
      may be done by clinical examination, ultrasound, or radiography--or a combination
      of these. Studies that have used clinical examination followed by ultrasound
      imaging for infants with certain risk factors have shown excellent results, but
      they were performed by very experienced practitioners. We wanted to find out
      whether the results of such screening would be equally good with less optimal
      staffing. Thus, we evaluated the real-life performance of a screening program for
      detection of congenital hip dysplasia in newborn infants. SUBJECTS AND METHODS:
      We performed a retrospective chart review of all infants (n = 1,983) referred for
      evaluation for suspected congenital hip dysplasia from one single obstetric
      hospital, where 19,820 infants had been screened from 1992 through 2001. Infants
      were referred either because of a positive finding during the Ortolani and Barlow
      examinations or because of the presence of risk factors. RESULTS: The reasons for
      referral of the 1,983 infants (10% of those examined) were: positive clinical
      signs in 255 (1.3% of all examined) and risk factors in 1,547 (7.8%), and a
      combination of both in 114 (0.6%). 67 other infants (0.3%) who had passed the
      initial pediatric screening were later referred from the local health centers.
      Finally, 23 of the 1,983 infants were subsequently referred again by their health
      center for renewed orthopedic evaluation. Of the infants who were treated
      (298/1,983 = 15% of those referred), those with a pathological examination result
      were represented proportionately more than infants who were referred because of
      risk factors (0.8% as opposed to 0.5%). Delayed diagnoses occurred in 1.7/1,000
      infants. INTERPRETATION: The performance of a screening protocol for congenital
      hip dysplasia in a real-life setting involving several physicians both on the
      pediatric and orthopedic side may not live up to expectations based on the use of
      such a protocol in an optimized setting. This type of analysis of screening data
      may serve to pinpoint weaknesses, and thus lead to adjustments that may enhance
      quality.

PMID- 18622834
TI  - Neonatal hip instability and risk of total hip replacement in young adulthood:
      follow-up of 2,218,596 newborns from the Medical Birth Registry of Norway in the
      Norwegian Arthroplasty Register.
AB  - BACKGROUND AND PURPOSE: Dysplasia is probably the most common underlying
      condition in osteoarthritis of the hip, leading to total hip replacement (THR) in
      young adulthood. We investigated whether hip instability at birth predisposes to
      THR in young adulthood. METHODS: Since 1967, all newborns in Norway have been
      screened for neonatal hip instability (NHI) and the results have been reported to
      the Medical Birth Registry of Norway (MBRN). In the period 1967-2004,2,218,596
      newborns were registered. From 1987 to 2004, 442 of these individuals had been
      reported to the Norwegian Arthroplasty Register (NAR) after undergoing total hip
      replacement (mean age 25 (12-36) years). RESULTS: Neonatal hip instability was
      reported in 19,432 newborns (0.88%) in the MBRN; according to the NAR, they had a
      2.6 (CI 1.4-4.8) times increased risk of THR in young adulthood compared to those
      without NHI. The absolute risk was low, however; only 57 (95% CI: 30-105) in
      10(5) for patients with NHI compared to 20 (95% CI: 18-22) in 10(5) for those
      without registered hip pathology. Of the 442 patients with THR, 95 were operated
      because of osteoarthritis of the hip secondary to dysplasia, according to the
      surgeon's report. However, only 8 of these 95 patients had been reported to have
      hip instability at birth. INTERPRETATION: Neonatal hip instability increases the
      risk of THR in young adulthood. Unexpectedly, only 8% of those who underwent THR
      due to dysplasia were reported to have unstable hips at birth. Our results
      indicate that clinical testing for NHI is insufficient as a screening method for
      dysplastic hips that require THR in young adulthood.

PMID- 18622835
TI  - Inferior outcome after intraoperative femoral fracture in total hip arthroplasty:
      outcome in 519 patients from the Danish Hip Arthroplasty Registry.
AB  - BACKGROUND: Intraoperative femoral fracture is a well known complication of
      primary total hip arthroplasty (THA). Experimental studies have indicated that
      intraoperative fractures may affect implant survival. Very few clinical data are
      available, however. METHODS: We used data from the Danish Hip Arthroplasty
      Registry to identify patients in Denmark who underwent a primary THA due to
      primary osteoarthritis between 1995 and 2005 (n = 39,478). Data were linked to
      two national Danish databases in order to conduct time-dependent implant survival
      analyses. Implant survival and relative risk estimates were calculated for
      patients treated nonoperatively and for patients treated with osteosynthesis
      after sustaining intraoperative femoral fractures during THA surgery. THAs
      performed without sustaining intraoperative femoral fracture served as the
      reference group. RESULTS: 282 patients (0.7%) were treated non operatively due to
      intraoperative femoral fracture and 237 patients (0.6%) were treated with
      osteosynthesis. In the 0-6 month postoperative period, the adjusted relative risk
      (RR) of revision was 1.5 (95% CI: 1.1-1.7) for patients treated nonoperatively
      and 5.7 (3.3-10) for patients treated with osteosynthesis. In the period from 6
      months to 11 years postoperatively, we did not find any statistically significant
      differences in the RR of revision between the groups. INTERPRETATION:
      Intraoperative fractures increase the relative risk of revision during the first
      6 postoperative months. Thus, patients should be informed about the risk of
      revision after sustaining an intraoperative femoral fracture. Furthermore,
      initiatives aimed at reducing the risk of revision in the first 6 months
      following THA should be considered in patients with intraoperative fractures,
      including immediate change to a larger stem with distal fixation and restricted
      weight bearing.

PMID- 18622836
TI  - Efficacy of antibiotic-impregnated cement in total hip replacement.
AB  - BACKGROUND AND PURPOSE: Antibiotic-impregnated cement is used as a spacer or
      during re-implantation surgery for the treatment of infected total hip
      arthroplasties. The routine use of antibiotic-impregnated cement during primary
      or uninfected revision total hip arthroplasty remains controversial. With this
      meta-analysis of the published literature, we intended to assess efficacy and
      safety in the use of antibiotic-impregnated cement for uninfected arthroplasty.
      METHODS: Following a detailed literature search, only studies reporting on the
      outcome of total hip replacement performed with antibiotic cement were included.
      Strict inclusion criteria were used and studies lacking sufficient sample size or
      critical data were excluded. 19 studies reporting on 36,033 hip replacements in
      35,659 patients met the initial inclusion criteria. The main aim of the meta
      analysis was to determine the rate of deep infection with and without the use of
      antibiotic cement, and to assess the revision rate and the ultimate survivorship
      of arthroplasty using antibiotic cement. RESULTS: The rate of deep infection
      following primary total hip arthroplasty, at 1.2%, was significantly lower when
      antibiotic cement was used than when cement without antibiotics was used (2.3%).
      Similarly, the rate of deep infection following revision total hip arthroplasty
      when a standard combination of cement and antibiotic--or a custom-made
      combination of cement and antibiotic, depending on the results of culture--was
      used, was almost half of the rate of deep infection when no antibiotics were
      present in the cement. Overall, the survivorship was 98% (101 failures in 5,178
      hips) for primary arthroplasty and 88% (100 failures in 855 hips) for revision
      arthroplasty. There were no reported adverse events or complications associated
      with the use of antibiotic-impregnated cement. INTERPRETATION: The use of
      antibiotic-impregnated cement lowered the infection rate by approximately 50% in
      primary hip arthroplasty. For revisions of previously infected hips, combinations
      or culture-dependent antibiotics lowered infection rates by approximately 40%.

PMID- 18622837
TI  - High levels of substance P and CGRP in pseudosynovial fluid from patients with
      aseptic loosening of their hip prosthesis.
AB  - BACKGROUND: Aseptic loosening is the most important complication after total hip
      arthroplasty (THA). The nervous system has been implicated in the etiology and
      pathogenesis of joint diseases. METHODS: We compared levels of substance P (SP)
      and calcitonin gene-related peptide (CGRP) in pseudosynovial fluid from patients
      with aseptic loosening after THA with those in synovial fluid from patients
      undergoing primary THA for osteoarthritis, who served as controls. Levels of SP
      and CGRP were measured using an enzyme immunoassay. RESULTS: We found that SP and
      CGRP levels were significantly higher in the pseudosynovial fluid of loose
      artificial joints than in the synovial fluid of controls. INTERPRETATION: SP and
      CGRP may have a role in aseptic loosening.

PMID- 18622838
TI  - A new technique for diagnosis of acetabular cup loosening using computed
      tomography: preliminary experience in 10 patients.
AB  - BACKGROUND AND PURPOSE: Considerable migration of the acetabular cup is required
      for diagnosis of loosening by conventional radiography. We have developed a new
      clinically applicable method for assessment of cup loosening using computed
      tomography (CT). PATIENTS AND METHODS: 10 patients scheduled for revision hip
      replacement due to suspected wear or loosening were scanned twice with CT under
      torsion loading of the prosthesis. Two independent examiners assessed each
      patient with respect to motion of the acetabular cup relative to the pelvis using
      CT volume registration. The CT measurements were compared to findings at revision
      surgery. RESULTS: The method was applicable in 8 of the 10 patients. 1 patient
      had a severe tremor. In 1 patient, surgery revealed that the hip was ankylotic
      due to massive ectopic bone formation. This left 8 patients that could be
      evaluated. 4 cups were loose at surgery, and 3 of these cups could be seen to be
      mobile by CT. 4 cups that were stable on revision were accurately diagnosed as
      not being mobile by CT. Movements of less than 1 millimeter between bone and
      prosthesis could not be distinguished from errors in CT acquisition and volume
      registration. There was good agreement between the two observers. INTERPRETATION:
      Movement of loose acetabular cups during torsion loading could be detected using
      CT volume registration. It was sensitive to cup movement in 3 out of 4 cases of
      loose cups. The method was specific and yielded no false positive results.

PMID- 18622839
TI  - Reconstruction of the medial patellofemoral ligament for treatment of patellar
      instability.

PMID- 18622840
TI  - Comparison of vacuum-formed removable rigid dressing with conventional rigid
      dressing after transtibial amputation: similar outcome in a randomized controlled
      trial involving 27 patients.
AB  - BACKGROUND AND PURPOSE: Following transtibial amputation, a rigid dressing of
      plaster of Paris has been reported to have advantages over a soft dressing
      regarding wound healing and reduction of edema, but use of the former may be
      limited by difficulties in application and in gaining access to the wound. An
      easily applicable and removable vacuum-formed rigid dressing (ORD) has recently
      been introduced. We compared the ORD with a conventional rigid plaster of Paris
      dressing with regard to wound healing, time to fitting of a prosthesis, and
      function with the prosthesis. METHOD: Patients undergoing transtibial amputation
      for peripheral vascular disease were randomized at surgery to receive ORD (O) or
      conventional rigid dressing (C) for 5 to 7 days, followed by compression therapy
      using silicone liner. The primary outcome measure was time to prosthetic fitting
      and secondary outcome measures included function with the prosthesis 3 months
      after amputation, measured with the Locomotor Capability Index (LCI) and the
      Timed "Up and Go" (TUG) test. All patients received prostheses with a total
      surface-bearing socket. RESULTS: Of 27 patients randomized to one or other
      dressing (15 O and 12 C), prosthetic fitting was achieved in 23 patients (mean
      age 76 (43-91) years; 13 (9 men) in the O group and 10 (5 men) in the C group).
      Wound healing was similar in both groups. Mean time to prosthetic fitting was 37
      (26-54) days in the O group and 34 (21-47) days in the C group (adjusted mean
      difference 3, 95% CI: -3-9). At 3 months, mean LCI was 28 (6-42) in the O group
      and 25 (2-41) in the C group (mean difference -0.1, 95% CI: -8.5-8.2). Mean TUG
      was 41 (10-92) seconds and 29 (10-47) seconds, respectively (mean difference 14,
      95% CI:-2-30). INTERPRETATION: The vacuum-formed rigid dressing appears to give
      results similar to those of the conventional rigid dressing regarding time to
      prosthetic fitting and patient's function with prosthesis.

PMID- 18622841
TI  - The proximally-based sural artery flap for coverage of soft tissue defects around
      the knee and on the proximal third and middle third of the lower leg: 10 patients
      followed for 1-2.5 years.
AB  - BACKGROUND AND PURPOSE: There have been few reports regarding the proximally
      based sural artery flap, which is useful for reconstruction of soft tissue
      defects around the knee and on the proximal third and middle third of the lower
      leg. Here we report our experience with 10 patients. PATIENTS: The defects in our
      10 cases were around the knee (4), on the proximal third of the lower leg (4),
      and on the middle third (2). 8 patients had fasciocutaneous flaps and 2 had
      adipofascial flaps. The flap size ranged from 4 to 10 cm in length, and from 5 to
      8 cm in width. The pedicle length ranged from 12 to 20 cm. RESULTS: All 10 flaps
      survived. Congestion and tip necrosis occurred in 1 case with a fasciocutaneous
      flap, which healed without complications. A superficial infection occurred in 1
      case with a fasciocutaneous flap, which healed with antibiotic treatment.
      Necrosis of grafted skin occurred in 2 cases of adipofascial flap; only one of
      them, however, required additional surgery. No morbidity of the donor site and no
      functional deficits were detected in any of the 10 cases. INTERPRETATION: The
      proximally based sural artery flap is useful for reconstruction of soft tissue
      defects around the knee joint and on the proximal third and middle third of the
      lower leg. It is a relatively easy and reliable procedure.

PMID- 18622842
TI  - Evaluation of a treatment protocol in distal radius fractures: a prospective
      study in 581 patients using DASH as outcome.
AB  - BACKGROUND AND PURPOSE: Distal radius fractures are most often treated
      nonoperatively, but sometimes they are treated surgically when deemed unstable.
      Based on the literature, a consensus protocol for treatment has been developed in
      southern Sweden to aid clinicians in their decision making. We evaluated the
      results of this protocol prospectively using a validated outcome instrument
      (DASH) in a large consecutive and population based series of unselected patients.
      METHODS: 581 patients were treated according the protocol. Age, sex, fracture
      side, and type of treatment were registered. The subjective outcome was measured
      by DASH. 133 patients were operated. RESULTS: 75% of the patients returned the
      questionnaire. The median DASH score at 3 months was 18.3 and at 12 months it was
      7.5. All treatment groups had low DASH scores at the final follow-up. Reduced,
      nonoperated fractures had a worse score (11.6) than undisplaced (4.2) or operated
      fractures (6.0). Age was the only other predictor, with older patients having a
      worse score. A correlation was found between the short-version 11-item QuickDASH
      questionnaire and the full 30-item DASH, both at 3 months (r = 0.98) and at 1
      year (r = 0.97) (p< 0.001 for both). INTERPRETATION: Most patients have residual
      symptoms at 3 months after the fracture but are normalized at 1 year. Good final
      subjective result was achieved with the proposed protocol regardless of initial
      severity and treatment of the fracture, as indicated by a low median DASH score
      in all groups. There was correlation between QuickDASH and the full DASH, and the
      former could be used in future studies.

PMID- 18622843
TI  - Cast and padding indices used for clinical decision making in forearm fractures
      in children.
AB  - PURPOSE: We assessed the reliability and practicality of two radiographic
      measurements--cast index and padding index--of the quality of plaster cast in
      clinical decision making in forearm fractures in children. METHODS: 40 orthopedic
      surgeons (20 consultants and 20 registrars) were asked to predict the risk of re
      displacement in 5 randomly selected cases. Subsequently, these surgeons were
      taught these indices and they were then requested to use them to predict re
      displacement. RESULTS: Every one of the 40 surgeons showed an increase in the
      number of correct responses. For consultants, the accuracy improved from 33% to
      72% and for the registrars it improved from 28% to 81%. This improvement was
      statistically significant. INTERPRETATION: We suggest that cast and padding
      indices are simple, reliable, and reproducible radio-graphic tools that can be
      used in clinics and wards to predict re-displacement of forearm fractures in
      children following initial reduction.

PMID- 18622844
TI  - Distal radial osteotomy for malunion using non-bridging external fixation: good
      results in 23 patients.
AB  - BACKGROUND AND PURPOSE: Symptomatic malunion of the distal radius is a common
      problem and is treated by distal radial osteotomy. Plating is commonly used but
      has a high rate of plate removal. This study is a report of the functional and
      radiographic outcome of a prospective series of distal radial osteotomies using
      non-bridging external fixation. METHODS: 23 patients with a median age of 60 (18
      84) years underwent distal radial osteotomy using non-bridging external fixation
      and bone grafting for dorsal malunion of a fracture of the distal radius. There
      were no cases of intraarticular malunion. Radiographic, functional, and patient
      assessed outcomes were assessed preoperatively and until 6 months after surgery.
      RESULTS: The mean preoperative dorsal angle of 20 (5-40) degrees was corrected to
      over 5 (0-15) degrees of volar tilt (p < 0.001) and the mean preoperative
      positive ulnar variance of 3.9 (0-8) mm was corrected to 2.5 (0-8) mm (p =
      0.005). Carpal alignment was restored in 22 of the 23 patients. 5 patients
      required simultaneous ulnar surgery, 1 required ulnar shortening, and 4 required
      modified Bower's procedures. By 6 months postoperatively, all measures of
      function except extension and key grip strength showed statistically significant
      improvements in their means. The SF36 showed statistical improvements in two
      domains, role physical and bodily pain. There were 2 patients with extensor
      pollicis longus ruptures and 13 with minor pin-track infections. INTERPRETATION:
      Distal radial osteotomy for dorsal malunion of the distal radius using non
      bridging external fixation is a successful technique for correction of deformity
      and restoration of function, with the advantages of being less invasive and not
      requiring further surgery for removal of metalwork.

PMID- 18622845
TI  - Identification of adverse events at an orthopedics department in Sweden.
AB  - BACKGROUND AND PURPOSE: Adverse events (AEs) are common in acute care hospitals,
      but there have been few data concerning AEs in orthopedic patients. We tested and
      evaluated a patient safety model (the Wimmera clinical risk management model) and
      performed a three-stage retrospective review of records to determine the
      occurrence of AEs in adult orthopedic inpatients. METHODS: The computerized
      medical and nursing records of 395 patients were included and screened for AEs
      using 12 criteria. Positive records were then reviewed by two senior orthopedic
      surgeons using a standardized protocol. An AE had to have occurred during the
      index admission or within the first 28 days of discharge from the Orthopedics
      Department. Screening of additional systems for reporting of AEs was also carried
      out for the same period. The number of patients suffering an AE and the number of
      AEs were recorded. RESULTS: Altogether, 60 (15 %) of 395 patients checked in the
      screening of records experienced 65 AEs (16%) due to healthcare management. Of
      the 65 AEs, 34 were estimated to have a high degree of preventability. 47 of the
      65 AEs occurred during the index admission and 18 within 28 days of discharge. In
      screening of local and nationwide reporting systems for the same patients, 4
      additional AEs were identified-2 of which were previously unknown. 67 different
      AEs were detected by using the Wimmera model (17%) INTERPRETATION: Using the
      Wimmera model with manual screening and review of records, many more AEs were
      detected than in all other traditional local and nationwide reporting systems
      used in Sweden when screening was done for the same period.

PMID- 18622846
TI  - 3-year follow-up of 215 fracture patients from a prospective and consecutive
      osteoporosis screening program. Fracture patients care!
AB  - BACKGROUND AND PURPOSE: Fractures can be prevented if osteoporosis is identified
      and treated. Starting in 2002, we have been using a screening program in which
      patients between 50 and 75 years of age with a wrist, shoulder, vertebral, or hip
      fracture are assessed by DEXA of the hip and spine and if osteoporotic or
      osteopenic, they are encouraged to see a doctor of their own choice. The patients
      receive documents containing information, the results of DEXA, and a letter to
      present to their doctor with suggestions regarding blood tests and treatment.
      Here we report the 3-year follow-up regarding compliance to the recommended
      treatment. METHODS: A questionnaire was sent to fracture patients who
      participated in the initial screening study from November 2002 through November
      2003. Questions included whether they had seen a doctor, whether treatment had
      been initiated, and their opinions about osteoporosis. RESULTS: 215 of the 236
      patients answered the questionnaire, with a mean follow-up of 39 months. 76/87 of
      those with osteoporosis, 70/99 of those with osteopenia, and 11/29 of those with
      normal BMD had seen a doctor. Anti-resorptive treatment was prescribed to two
      thirds of the osteoporotic patients, to one-sixth of the osteopenic patients, and
      to none of the patients with normal bone density. Calcium-vitamin D
      supplementation as monotherapy was given to one-third of the osteoporotic
      patients, to half of the osteopenic patients, and to half of the normal patients.
      Only a few osteoporotic patients, one-third of the osteopenic patients, and half
      of the normal patients received no treatment. Compliance to treatment was 80%
      over 3 years in those treated. Most patients felt that they could influence their
      skeletal health. INTERPRETATION: Screening of fracture patients for osteoporosis
      effectively identifies patients with low bone mineral density and the patient can
      be trusted to seek appropriate medical advice for treatment of osteoporosis.
      Based on the bone scan diagnosis, the treatment that these patients received
      reflects current treatment guidelines well.

PMID- 18622847
TI  - Bone formation in interleukin-4 and interleukin-13 depleted mice.
AB  - BACKGROUND AND PURPOSE: Cytokines play an important role in the complex process
      of bone formation. We have previously found an altered skeletal phenotype with
      reduction of cortical bone mass in mice depleted of the 2 cytokines interleukin-4
      (IL-4) and interleukin-13 (IL 13). The present study was performed to investigate
      a potential role of IL-4 and IL-13 in fracture healing and bone induction by
      demineralized xenogenic bone matrix (DXBM). METHODS: Callus formation in IL-4-(/)
      IL-13-(/)- (IL-4/13 knockout) and wild-type (WT) male mice was compared using a
      standardized fracture model. The capacity of IL-4(-/-)IL-13(-/-) and WT male and
      female mice to form heterotopic bone was compared using intramuscular implants of
      DXBM. Bone formation and mechanical properties were evaluated by pQCT, ash
      weight, 3-point bending, radiology, and immunohistology. RESULTS: In the fracture
      investigation substantial amounts of new bone formation by 5 weeks were found,
      but no differences in radiographical healing, callus volume, BMD, BMC, or
      mechanical properties were detected between IL-4(-/-)IL-13(-/-) and WT mice. In
      the DXBM investigation radiographic analysis confirmed mineralization of implants
      in both groups, but no difference in the amount of mineral deposition (net bone
      formation) between IL-4(-/-)IL-13(-/-) and WT mice was found. Immunohistology
      showed inhibition of autonomic nerves in the capsule of the IL-4(-/-)IL-13(-/-)
      group along with a lack of vascularization within the implants. INTERPRETATION:
      Depletion of IL-4 and IL-13 does not cause any major alteration in fracture
      healing or heterotopic bone formation in mice. The pattern of autonomous nerve
      expression and expression of markers of neovascularization is, however, altered
      to some extent by the absence of IL-4 and IL-13.

PMID- 18622848
TI  - Nanoparticulate fillers improve the mechanical strength of bone cement.
AB  - BACKGROUND AND PURPOSE: Polymethylmethacrylate (PMMA-) based bone cement contains
      micrometer-size barium sulfate or zirconium oxide particles to radiopacify the
      cement for radiographic monitoring during follow-up. Considerable effort has been
      expended to improve the mechanical qualities of cements, largely through
      substitution of PMMA with new chemical structures. The introduction of these
      materials into clinical practice has been complicated by concerns over the
      unknown long-term risk profile of these new structures in vivo. We investigated a
      new composite with the well characterized chemical composition of current
      cements, but with nanoparticles instead of the conventional, micrometer-size
      barium sulfate radiopacifier. METHODS: In this study, we replaced the barium
      sulfate microparticles that are usually present in commercial PMMA cements with
      barium sulfate nanoparticles. The resultant "microcomposite" and "nanocomposite"
      cements were then characterized through morphological investigations such as
      ultra-small angle X-ray scattering (USAXS) and scanning electron microscopy
      (SEM). Mechanical characterization included compression, tensile, compact
      tension, and fatigue testing. RESULTS: SEM and USAXS showed excellent dispersion
      of nanoparticles. Substitution of nanoparticles for microparticles resulted in a
      41% increase in tensile strain-to-failure (p = 0.002) and a 70% increase in
      tensile work-of-fracture (p = 0.005). The nanocomposite cement also showed a two
      fold increase in fatigue life compared to the conventional, microcomposite
      cement. INTERPRETATION: In summary, nanoparticulate substitution of
      radiopacifiers substantially improved the in vitro mechanical properties of PMMA
      bone cement without changing the known chemical composition.

PMID- 18622849
TI  - C-reactive protein levels for early detection of postoperative infection after
      fracture surgery in 787 patients.
AB  - BACKGROUND AND PURPOSE: For early detection of postoperative infections, the
      level of C-reactive protein (CRP) may be useful. We analyzed baseline and time
      dependent reference values for the postoperative use of CRP as an indicator of
      infection. METHODS: We studied the kinetics of CRP levels after fracture surgery
      in 1,418 patients. In 787 cases the operative fracture treatment was uneventful;
      in 17 of the other cases a deep wound infection occurred. RESULTS: In the
      uneventful cases, a similar evolution in CRP concentrations was found: the peak
      level, which occurred on the second postoperative day, depended on the region
      (136 mg/L in femoral fractures and 45 mg/L in ankle fractures) and reflected the
      extent of surgical trauma. For deep wound infection, a cutoff level of 96 mg/L
      (sensitivity 92%, specificity 93%) after the fourth day of surgery was recorded.
      INTERPRETATION: CRP kinetics permit establishment of a time-dependent set of
      reference values of CRP after operative fracture treatment. Deviations of this
      course--especially CRP concentrations above 96 mg/L after the fourth day--may aid
      in early detection of surgical complications.

PMID- 18622850
TI  - Colibacillosis in poultry: unravelling the molecular basis of virulence of avian
      pathogenic Escherichia coli in their natural hosts.
AB  - Avian colibacillosis is caused by a group of pathogens designated avian
      pathogenic Escherichia coli (APEC). Despite being known for over a century, avian
      colibacillosis remains one of the major endemic diseases afflicting the poultry
      industry worldwide. Autologous bacterins provide limited serotype-specific
      protection, yet multiple serogroups are associated with disease, especially O1,
      O2 and O78 among many others. Experimental infection models have facilitated the
      identification of some key APEC virulence genes and have allowed testing of
      vaccine candidates. Well-recognized virulence factors include Type 1 (F1) and P
      (Pap/Prs) fimbriae for colonization, IbeA for invasion, iron acquisition systems,
      TraT and Iss for serum survival, K and O antigens for anti-phagocytic activity,
      and a temperature-sensitive haemagglutinin of imprecise function. Intriguingly,
      these factors do not occur universally among APEC, suggesting the presence of
      multiple alternative mechanisms mediating pathogenicity. The recent availability
      of the first complete APEC genome sequence can be expected to accelerate the
      identification of bacterial genes expressed during infection and required for
      virulence. High-throughput molecular approaches like signature-tagged transposon
      mutagenesis have already proved invaluable in revealing portfolios of genes
      expressed by pathogenic bacteria during infection, and this has enabled
      identification of APEC O2 factors required for septicaemia in the chicken model.
      Complimentary approaches, such as in vivo-induced antigen technology, exist to
      define the activities of APEC in vivo. In recent years, reverse vaccinology and
      immuno-proteomic approaches have also enabled identification of novel vaccine
      candidates in other bacterial pathogens. Collectively, such information provides
      the basis for the development or improvement of strategies to control APEC
      infections in the food-producing avian species.

PMID- 18622851
TI  - The role of oxidative stress in the development of congestive heart failure in a
      chicken genotype selected for rapid growth.
AB  - The present study examined the possible role of reactive oxygen species in the
      pathogenesis of heart failure in broilers. Data were collected from three groups
      of birds at various risk of heart failure: Leghorn chickens (resistant to heart
      failure), slow-growing feed-restricted broilers (low risk of heart failure), fast
      growing ad libitum fed broilers (high risk of heart failure), and broilers with
      congestive heart failure (CHF). In the first part of the study, basic clinical
      parameters and ultrastructural changes were examined in the context of lipid
      peroxidation of the ventricular myocardium. This was followed by the study of in
      vitro changes in the activity of selected cytosolic enzymes (creatine kinase and
      lactate dehydrogenase) and mitochondrial enzymes (pyruvate dehydrogenase and
      alpha-ketoglutarate dehydrogenase) in the presence of oxidants (hydrogen peroxide
      or tertiary butyl hydroperoxide). The distinctive clinical feature in the fast
      growing broilers and in the broilers with CHF as compared with slow-growing
      broilers or Leghorn chickens was a significantly lower heart rate (P <0.05).
      Electron microscopy revealed marked morphological changes in myocardial
      mitochondria in these broilers (i.e. fast-growing broilers and broilers with
      CHF). The level of malondialdehyde equivalents, an indicator of lipid
      peroxidation subsequent to generated oxidative stress, was significantly higher
      (P <0.05) in ad libitum fed broilers and was highest (P <0.01) in broilers with
      CHF. In vitro, the presence of oxidants had a detrimental effect on creatine
      kinase and alpha-ketoglutarate dehydrogenase activity, while lactate
      dehydrogenase activity increased. The activity of pyruvate dehydrogenase was not
      altered by oxidants. Our results indicate that the deterioration of heart
      function in fast-growing commercial broilers in our experimental model is
      associated with oxidative stress leading to lipid peroxidation of cellular and
      mitochondrial membranes, and decreased activity of myocardial creatine kinase and
      alpha-ketoglutarate dehydrogenase enzymes critical for energy synthesis and
      transformation pathways.

PMID- 18622852
TI  - Molecular epidemiology of a reproductive tract-associated colibacillosis outbreak
      in a layer breeder flock associated with atypical avian pathogenic Escherichia
      coli.
AB  - The molecular epidemiology of 70 Escherichia coli isolates from an infection
      outbreak in a layer breeder flock was examined by pulsed-field gel
      electrophoresis and for a range of virulence factors by polymerase chain
      reaction. Pulsed-field gel electrophoresis showed 35 of 45 isolates from eight
      disease cases were associated with a single clonal group that was the exclusive
      strain associated with reproductive tract. A second unrelated group was found in
      environmental isolates and healthy birds. The remaining isolates were unrelated
      to each other or either clonal group. Polymerase chain reaction virulotyping
      indicated the "epidemic" clonal group contains virulence factors including iss,
      sfa, tsh, iucC, ibeA, and sitA associated with avian pathogenic E. coli plus
      several virulence factors more normally associated with human urinary tract
      infection. Significantly, the "epidemic" clone was also found in an environmental
      sample, suggesting it may have been transmitted to the flock via the environment.

PMID- 18622853
TI  - Short-chain fatty acids and L-lactate as feed additives to control Campylobacter
      jejuni infections in broilers.
AB  - The usefulness of butyrate, acetate, propionate and l-lactate for the control of
      Campylobacter jejuni infections in broilers was assessed. For this purpose, the
      effect of these acids on the growth of C. jejuni in broth and intestinal mucous
      was determined, as well as their influence on the invasiveness of C. jejuni in
      intestinal epithelial cells. From these in vitro obtained results, one acid was
      retained for use as a feed additive in an in vivo trial. Butyrate was the most
      successful of the short-chain fatty acids, with 12.5 mM being bactericidal for C.
      jejuni at pH 6.0. Propionate and acetate had a bacteriostatic effect at 50 mM.
      None of the short-chain fatty acids had a bactericidal effect at pH 7.5 at a
      maximum concentration of 50 mM. Mucous increased the minimum bactericidal
      concentration of butyrate, but not the bacteriostatic concentrations of
      propionate or acetate. When C. jejuni was incubated in growth subinhibitory
      concentrations of butyrate, acetate or propionate or 25 mM L-lactate, no
      alteration in the invasive capabilities of C. jejuni in Caco-2 cells was
      observed. The addition of butyrate-coated micro-beads to the feed was
      unsuccessful to reduce C. jejuni caecal colonization in a seeder model using 2
      week-old broilers. In conclusion, despite the marked bactericidal effect of
      butyrate towards C. jejuni in vitro, butyrate-coated micro-beads do not protect
      broilers from caecal colonization with C. jejuni in the applied test conditions.
      This might be partially ascribed to the protective effect of mucous and the rapid
      absorption of butyrate by the enterocytes.

PMID- 18622854
TI  - Detection and quantification of Mycoplasma gallisepticum genome load in
      conjunctival samples of experimentally infected house finches (Carpodacus
      mexicanus) using real-time polymerase chain reaction.
AB  - A TaqMan-based real-time, quantitative polymerase chain reaction (qPCR) assay
      utilizing the mgc2 gene was developed to detect Mycoplasma gallisepticum in
      conjunctival swabs of experimentally infected house finches. The assay was
      demonstrated to be quantitative by the standard curve method with reproducible
      results within runs and between runs. The detection limit of the mgc2 assay was
      examined using two standards. The test had a detection limit of less than 14
      copies per reaction when tested with a plasmid standard and less than 10 copies
      per reaction when tested with M. gallisepticum genomic DNA. All M. gallisepticum
      negative birds (10 specific pathogen free chickens and 10 house finches) were
      negative by mgc2 qPCR assay. Existing evidence suggests that an important part of
      M. gallisepticum pathogenesis includes both its attachment to and invasion of
      host cells. Thus, our test also made use of rag-1 as an internal control gene.
      The rag-1 qPCR results showed that host cell quantity varied greatly between
      conjunctival samples. After inoculation, M. gallisepticum levels in the house
      finch conjunctiva increased over the 7-day period post infection. The bird with
      the most pronounced clinical conjunctivitis harboured the highest level of M.
      gallisepticum and the bird that did not develop conjunctivitis had very low
      numbers of M. gallisepticum. Thus, it appears that development of conjunctivitis
      may correlate with M. gallisepticum load.

PMID- 18622855
TI  - Experimental infections of herring gulls (Larus argentatus) with H5N1 highly
      pathogenic avian influenza viruses by intranasal inoculation of virus and
      ingestion of virus-infected chicken meat.
AB  - The present study investigated the susceptibility of herring gulls (Larus
      argentatus) exposed to two strains of Asian lineage H5N1 highly pathogenic avian
      influenza (HPAI) virus by evenly separating six gulls into two groups and
      inoculating them intranasally with 10(6) median embryo infectious doses of either
      A/whooper swan/Mongolia/244/05 (H5N1) or A/duck meat/Anyang/AVL-1/01 (H5N1). Two
      additional gulls were fed 5.0 g meat from a specific pathogen free chicken that
      died after experimental infection with A/whooper swan/Mongolia/244/05. Morbidity
      and mortality were observed in the gulls infected with A/whooper
      swan/Mongolia/244/05 by both routes of exposure. Gulls infected with A/duck
      meat/Anyang/AVL-1/01 exhibited high morbidity, but no mortality. The
      concentration and duration of viral shedding were similar between gulls infected
      with either strain of H5N1 HPAI virus by intranasal inoculation and gulls exposed
      to A/whooper swan/Mongolia/244/05 through ingestion of virus-infected chicken
      meat. The susceptibility of herring gulls in this study varied between the two
      strains of Asian lineage H5N1 HPAI virus. These results also provide preliminary
      data to support that ingestion of virus-infected raw or uncooked chicken meat is
      a viable route of exposure to some H5N1 HPAI viruses in herring gulls. Additional
      studies are necessary to further evaluate the efficiency of this route of
      exposure to a variety of H5N1 HPAI virus strains in herring gulls and other avian
      species in order to better understand the potential role of scavenging species in
      the epidemiology of H5N1 HPAI virus.

PMID- 18622856
TI  - A comparative study on the pathogenesis of egg contamination by different
      serotypes of Salmonella.
AB  - Salmonella enterica serotype Enteritidis is the predominant serotype associated
      with egg-borne salmonellosis in humans. Apparently this serotype possesses
      particular characteristics that increase its chance to contaminate eggs. To
      identify these characteristics, two Salmonella serotype Enteritidis strains as
      well as one strain of each of the serotypes Salmonella Typhimurium, Salmonella
      Heidelberg, Salmonella Virchow and Salmonella Hadar strain were used to examine
      different aspects related to egg contamination. After an intravenous infection of
      laying hens, it was observed that the ability of the serotype Enteritidis strains
      to colonize the reproductive organs was significantly higher compared with the
      Salmonella Heidelberg, Salmonella Virchow and Salmonella Hadar strains but not
      with the Salmonella Typhimurium strain. Inoculating low numbers of the different
      Salmonella serotypes in egg albumen at 42 degrees C demonstrated that the growth
      of the strains belonging to the Salmonella serotypes Virchow and Hadar was
      seriously repressed. The other serotypes, however, survived in albumen for 24 h.
      Furthermore, using two different specifically designed egg infection models, it
      was shown that all strains used in this study were able to penetrate into and
      multiply inside the yolk at 25 degrees C. These findings indicate that the
      ability to grow in eggs post lay is not specific for the serotype Enteritidis. In
      conclusion, comparing strains belonging to different Salmonella serotypes has
      revealed that most probably a preferential colonization of the reproductive
      organs and an enhanced survival at 42 degrees C allows the serotype Enteritidis
      to contaminate eggs.

PMID- 18622858
TI  - First description of malignant retrobulbar and intracranial teratoma in a lesser
      kestrel (Falco naumanni).
AB  - Teratomas are defined as germ cell origin neoplasms that can be rarely found in
      either humans or animals. Their most common localization is the gonads, although
      extragonadal localization has also been observed. In avian medicine, there is
      scarce literature about the occurrence of teratomas and their clinical
      implications, and this is mainly in wildlife birds . For this reason, we report
      the first description of a teratoma with both retrobulbar and intracranial
      locations in a 10-day-old chick of a lesser kestrel (Falco naumanni) born in
      captivity. The raptor was treated in a centre of wildlife rehabilitation because
      of the presence of left periocular swelling and exopthalmos. The bird worsened
      rapidly with signs of vestibular syndrome, ataxia and depression, and euthanasia
      was practised for humanitarian reasons. Histological examination characterized
      both masses as malignant teratomas based on the presence of tissues of the three
      germ cell layers and the presence of both anaplastic foci and immature tissues.

PMID- 18622857
TI  - Conventional inactivated bivalent H5/H7 vaccine prevents viral localization in
      muscles of turkeys infected experimentally with low pathogenic avian influenza
      and highly pathogenic avian influenza H7N1 isolates.
AB  - Highly pathogenic avian influenza (HPAI) viruses cause viraemia and systemic
      infections with virus replication in internal organs and muscles; in contrast,
      low pathogenicity avian influenza (LPAI) viruses produce mild infections with low
      mortality rates and local virus replication. There is little available
      information on the ability of LPAI viruses to cause viraemia or on the presence
      of avian influenza viruses in general in the muscles of infected turkeys. The aim
      of the present study was to determine the ability of LPAI and HPAI H7N1 viruses
      to reach muscle tissues following experimental infection and to determine the
      efficacy of vaccination in preventing viraemia and meat localization. The
      potential of infective muscle tissue to act as a source of infection for
      susceptible turkeys by mimicking the practice of swill-feeding was also
      investigated. The HPAI virus was isolated from blood and muscle tissues of all
      unvaccinated turkeys; LPAI could be isolated only from blood of one bird and
      could be detected only by reverse transcriptase-polymerase chain reaction in
      muscles. In contrast, no viable virus or viral RNA could be detected in muscles
      of vaccinated/challenged turkeys, indicating that viral localization in muscle
      tissue is prevented in vaccinated birds.

PMID- 18622859
TI  - In vitro antibiotic susceptibility of Dutch Mycoplasma synoviae field isolates
      originating from joint lesions and the respiratory tract of commercial poultry.
AB  - The in vitro susceptibility of 17 Dutch Mycoplasma synoviae isolates from
      commercial poultry to enrofloxacin, difloxacin, doxycycline, tylosin and
      tilmicosin was examined. Three isolates originated from joint lesions and 14 were
      from the respiratory tract. The type strain M. synoviae WVU 1853 was included as
      a control strain. Antibiotic susceptibility was tested quantitatively using the
      broth microdilution test. Based on initial and final minimum inhibitory
      concentration values, all tested isolates were susceptible to doxycycline,
      tylosin and tilmicosin. Two isolates from the respiratory tract were resistant to
      enrofloxacin and showed intermediate resistance to difloxacin.

PMID- 18622860
TI  - Persistence of Salmonella Senftenberg in poultry production environments and
      investigation of its resistance to desiccation.
AB  - Most Salmonella serovars, including Salmonella enterica subsp. enterica serovar
      Senftenberg (S. Senftenberg), are tolerant to desiccation and able to colonize
      and persist in feed mills. In addition, they may survive cleaning and
      disinfection procedures used on poultry farms. The present study was conducted to
      investigate the survival of S. Senftenberg in broiler parent stock farms and
      broiler farms. The isolates from one of the parent stock farms investigated only
      differed by a single band in fluorescent amplified fragment-length polymorphism
      analysis and had identical pulsed-field gel electrophoresis profiles, indicating
      that a S. Senftenberg clone had persisted for more than 2 years, despite
      cleaning, disinfection, desiccation and depopulation, and was subsequently able
      to infect Salmonella-free layers. Isolates from the same house on a different
      broiler parent stock farm were found to be identical by amplified fragment-length
      polymorphism analysis and pulsed-field gel electrophoresis although the farm
      tested negative for Salmonella 55 times over a period of 18 months between the
      two positive samplings. An assay was developed to investigate the survival of 34
      S. Senftenberg isolates during desiccation at approximately 38% relative
      humidity. On average, the viability of S. Senftenberg isolates decreased by 1000
      fold over 35 days. The persistent clones were no more resistant to desiccation
      than the other isolates investigated. However, S. Senftenberg was more resistant
      to desiccation than an isolate of Pantoea agglomerans commonly found on poultry
      feed-processing lines. This study demonstrates the risk of persistence of feed
      associated serovars such as S. Senftenberg.

PMID- 18622861
TI  - Comparative study on the pathogenicity and immunogenicity of wild bird isolates
      of avian paramyxovirus 2, 4, and 6 in chickens.
AB  - Based on the haemagglutination inhibition assay, nine antigenically distinct
      serotypes of avian paramyxoviruses (APMV) are described. Isolates from APMV 2, 3,
      6 and 7 can cause respiratory symptoms and/or problems of the reproductive tract
      that may produce complications if secondary infections occur, while isolates from
      APMV 4, 5, 8 and 9 rarely produce clinical signs in species from which they are
      isolated. Isolates belonging to the APMV 1 subtype induce a wide range of disease
      symptoms varying from mild symptoms to a disease with devastating consequences as
      caused by velogenic Newcastle disease virus. In this report, one isolate each of
      APMV 2, 4, and 6 were isolated from wild birds and subsequently characterized in
      specific pathogen free chickens. All three isolates caused no clinical symptoms
      but showed microscopic lesions in the trachea, lungs, gut, and pancreas
      characteristic for a viral infection. Interestingly, only APMV 2 induced
      haemagglutination inhibition antibodies, while haemagglutination inhibition
      antibodies of chickens infected with APMV 4 and 6 were not detected. The
      replication of the virus in the birds was confirmed by isolation of the virus in
      embryonated eggs.

PMID- 18622862
TI  - Partial genome sequence analysis of parvoviruses associated with enteric disease
      in poultry.
AB  - Poult enteritis mortality syndrome (PEMS) of turkeys and runting-stunting
      syndrome (RSS) of chickens are significant viral enteric diseases of poultry.
      Although a number of different viruses, including avian reoviruses, rotaviruses,
      astroviruses and coronaviruses, have been isolated from the intestinal contents
      of birds in affected poultry flocks, their role in PEMS and RSS is not yet
      understood. Here, we report the application of a molecular screening method to
      detection of novel viruses in intestinal samples of chickens and turkeys
      exhibiting characteristic signs of enteric disease. The technique is based on
      random amplification of particle-associated nucleic acids in clinical samples.
      Using this method we successfully identified parvovirus DNA sequences in
      intestinal homogenates of affected birds. This is the first time partial genomic
      sequences of autonomously replicating chicken and turkey parvoviruses have been
      described. Sequence analysis of the left end of the genome, including the
      complete non-structural gene, demonstrated that the chicken and turkey
      parvoviruses were closely related to each other and were representative of a
      novel member of the Parvovirus family. These parvoviruses may play a significant
      role in the aetiology of PEMS and RSS.

PMID- 18622863
TI  - Mycobacteriosis in naturally infected ring-neck doves (Streptopelia risoria):
      investigation of the association between feather colour and susceptibility to
      infection, disease and lesions type.
AB  - Prevalence of infection and disease, the degree of organ involvement and the
      nature of the lesions were investigated in 11 white and 18 non-white ring-neck
      doves coming from a flock naturally infected with Mycobacterium avium subsp.
      avium. Lesions were common in the liver, spleen, lung, kidney, intestines, ovary
      and bone marrow. Overall, 18 out of 29 (62%) birds were considered infected with
      a sequevar of M. avium subsp. avium that contains serotypes 2, 3, 4 and 9. The
      prevalence of infection in the white doves (36.4%) was significantly lower than
      in the non-white morphs (77.7%). White doves had on average fewer organs affected
      (mean =3.1) than the non-white doves (mean =5.9). A diffuse pattern of
      inflammation in the liver and spleen was observed mainly in non-white doves.
      Focal or multifocal granulomatous inflammation of the liver and spleen was
      predominant in white doves. Genetic mechanisms of immunity to mycobacteriosis may
      be contributing or determining these differences. There are three basic colour
      morphs in ring-neck doves--dark or wild type, blond and white--and the alleles
      coding for colour are sex-linked and located on the sex (Z) chromosome. Female's
      single sexual chromosomed (ZW) and homozygous males (ZZ) can be white if they
      carry the white alleles. It is very probable that the gene or genes modulating
      the immune response to M. avium subsp. avium infection in these doves could be
      associated to these loci or at least located in the same (Z) chromosome, as the
      association with white colour suggests.

PMID- 18622865
TI  - Direct detection of infectious bursal disease virus from clinical samples by in
      situ reverse transcriptase-linked polymerase chain reaction.
AB  - The presence of the very virulent (vv) Brazilian strain of infectious bursal
      disease virus (IBDV) was determined in the bursa of Fabricius, thymus and liver
      of 2-week-old broilers from a flock with a higher than expected mortality. For
      this purpose, a direct in situ reverse transcriptase (RT)-linked polymerase chain
      reaction (PCR) method was developed using specific primers for vvIBDV. Unlabelled
      forward and reverse biotinylated oligonucleotides were used for RT-PCR in a one
      step method and the respective products were revealed by a direct enzymatic
      reaction. The results were compared with those obtained by standard RT-PCR using
      general primers for IBDV and virus isolation. The virus isolation, RT-PCR and in
      situ RT-PCR revealed positive results on the bursa of Fabricius in 86%, 80% and
      100%, respectively. The in situ RT-PCR detected vvIBDV in all tested thymus and
      liver samples, whereas the standard RT-PCR detected virus in 80% and 90% of the
      samples, respectively. After three consecutive passages on chicken embryonated
      eggs, IBDV was isolated from 64% of the thymus samples and 30% of the liver
      samples. In the present study, no classical or antigenic variants of IBDV were
      detected. The developed in situ RT-PCR assay was able to detect the very virulent
      strain of IBDV with a higher sensitivity than the conventional RT-PCR and virus
      isolation.

PMID- 18622864
TI  - Detection of reticuloendotheliosis virus by immunohistochemistry and in situ
      hybridization in experimentally infected Japanese quail embryos and archived
      formalin-fixed and paraffin-embedded tumours.
AB  - Reticuloendotheliosis virus (REV) infection can result in immunosuppression, a
      runting syndrome, high mortality, acute reticulum cell neoplasia, or T-cell
      and/or B-cell lymphomas, in a variety of domestic and wild birds.
      Histopathological changes in REV infection are not sufficient to differentiate it
      from avian lymphoid leukosis and Marek's disease, and currently there are no
      available in situ diagnostic methods for detection of active REV presence in
      pathologic specimens. To develop immunohistochemistry and in situ hybridization
      assays for detection of REV active infections, experimentally inoculated Japanese
      quail embryos, and archived formalin-fixed paraffin-embedded tissues from natural
      and experimental reticuloendotheliosis cases in chickens and turkeys, were
      examined. The in situ hybridization and immunohistochemistry assays proved to be
      efficient for the detection of several REV strains in Japanese quail embryos
      during active infection, whereas these assays were much less sensitive when
      applied to archived tissue samples from chronically infected birds with lymphoid
      tumours. The diagnostic assays developed in this study have potential as
      diagnostic tools for detection of active REV infections.

PMID- 18622867
TI  - Reduction by dietary matrix metalloproteinase inhibitor BAY 12-9566N of
      neoplastic development induced by diethylnitrosamine, N-nitrosodimethylamine, or
      7,12-dimethylbenz(a)anthracene in rats.
AB  - BAY 12-9566N (BAY), which is a substituted 4-biarylbutyric acid and has the
      properties of a matrix metalloproteinase (MMP) inhibitor, was tested in the
      accelerated cancer bioassay (ACB). In the ACB, three different genotoxic
      carcinogens were administered individually to groups of male and female Wistar
      rats, in initiation (IN) segments lasting 10 weeks, followed by BAY in promotion
      segments lasting 42 weeks, for a total of 52 weeks of treatment, followed by 12
      weeks of recovery. The IN target organs in males were the liver using
      diethylnitrosamine (DEN), and the lungs, using N-nitrosodimethylamine (NDA), and
      in females, the mammary gland using 7,12-dimethylbenz(a)anthracene (DMBA). The
      study consisted of eight groups of 24 rats each as follows: controls (male and
      female), DEN alone (male), DEN/BAY (male), NDA (male), NDA/BAY (male), DMBA
      (female), and DMBA/BAY (female). The daily dose of BAY was 240 mg/kg in the diet,
      yielding a cumulative dose of 70,560 mg/kg. The cumulative doses of carcinogens
      were 220 mg/kg DEN, 150 mg/kg NDA, or 15 mg/kg DMBA. No significant difference in
      body-weight gain pattern was evident between any of the groups at 52 or 64 weeks.
      Rather, in males, DEN-induced hepatocellular adenomas were reduced with BAY
      treatment from 29% to 21% (p < 0.05) and carcinomas from 42% to 29% (p < 0.01).
      Also, in males, NDA-induced pulmonary adenomas were reduced with BAY treatment
      from 38% to 21% (p < 0.01) and carcinomas from 21% to 4% (p < 0.01). In females,
      DMBA-induced mammary gland adenomas were reduced from 13% to 4% (p < 0.01) and
      carcinomas from 54% to 42% (p < 0.05). Thus, BAY produced a consistent and
      significant reduction of neoplasm development in both genders in three target
      tissues of carcinogenicity in which neoplasms were induced by three different DNA
      reactive initiators. This inhibition may be due to inhibition of MMP, leading to
      reduced neoplastic growth and development.

PMID- 18622868
TI  - Subchronic, reproductive, and developmental toxicity of a fluorotelomer-based
      urethane polymeric product.
AB  - A commercial fluorotelomer-based urethane polymeric dispersion, consisting of
      polymer, surfactant, and water, was evaluated in subchronic, reproduction, and
      developmental toxicity studies. The dispersion was administered daily by gavage
      to rats at dosages of 0, 50, 250, or 1000 mg polymer/kg/day or with 70 mg/kg/day
      of the sulfonate surfactant. Dose levels of 0, 50, 250, or 1000 mg polymer/kg/day
      were also used for the reproductive and developmental studies. Nasal olfactory
      epithelial degeneration and necrosis occurred in all dose groups in the 90-day
      study. Nasal adhesions were observed only in rats administered surfactant alone.
      Liver-enzyme alterations at 250 and 1000 mg/kg were considered to be potentially
      adverse effects. The subchronic no-observed-adverse-effects level (NOAEL) was 50
      mg/kg. For the reproduction study, rats were dosed for 10 weeks prior to
      cohabitation and throughout mating, gestation, and lactation. There were no
      effects on reproductive function in males or females at any dosage. Thyroid
      weight was decreased in the 250 and 1000 mg/kg day F(1) groups unaccompanied by
      microscopic effects. In the developmental toxicity study, female rats were dosed
      from gestation days 6-20; there was no test-substance-related embryolethality,
      nor was there any dose-related increase in either fetal malformations. Fetal
      weight was minimally decreased at 1000 mg/kg/day in the presence of slight
      maternal toxicity; the NOAEL for developmental parameters was 250 mg/kg/day. The
      polymeric product was not a specific developmental or reproductive toxin.

PMID- 18622869
TI  - Cytotoxicity of fumonisin B(1) in spheroid and monolayer cultures of rat
      hepatocytes.
AB  - Fumonisin B(1) (FB(1)), the most prevalent member of toxins produced by several
      species of Fusarium molds, which occur mainly in maize, causes several fatal
      hepatopathies and nephropathies of animals. The current study was scrutinized to
      ascertain different cytotoxic and morphological transformations in rat
      hepatocytes induced by the treatments of diverse concentrations (300, 500, or
      1000 microM) of fumonisin B(1) in vitro, using both monolayer and spheroid
      cultures. In each hepatocyte culture, the cytotoxicity of FB(1) was augmented in
      dose- and time-response manners. Morphological transformations among FB(1)
      treated groups integrated accumulation of lipid droplets, cytoplasmic vacuolation
      in hepatocyte monolayers, and bleb formation in the hepatocyte spheroids.
      Additionally, electron microscopy revealed the loss of microvilli, mitochondrial
      swelling, and formation of lamellar membranous whorl in the vacuoles and bile
      canaliculi-like structures. Appearance of electron dense bodies in the
      monolayers, and loss of cell-to-cell contact in spheroids were depicted in 1000
      microM FB(1)-treated hepatocytes. These outcomes insinuate different vital events
      in explaining morphological transformations in the cell membrane and organelles,
      induced by fumonisins in rat hepatocytes.

PMID- 18622870
TI  - Modulation of fenthion-induced oxidative effects by BSO in the liver of Cyprinus
      carpio L.
AB  - The objective of the present study was to evaluate the oxidative stress potential
      of low-level organophosphate fenthion exposure with the modulatory effect of
      buthionine sulfoximine in the liver of Cyprinus carpio L. The fish were exposed
      to 20% of 96-hour LC(50) of fenthion for 24 and 96 hours. Total and oxidized
      glutathione, thiobarbituric acid reactive substances, protein levels, glutathione
      peroxidase, glutathione reductase, glutathione-S-transferase, superoxide
      dismutase, and catalase-specific enzyme activities were measured
      spectrophotometrically. There was a 15-day depuration period to evaluate the
      changes in the studied parameters. Fenthion caused a time-dependent depletion of
      the total and reduced glutathione levels. The oxidized/reduced glutathione ratio
      and catalase specific enzyme activity were reduced while the glutathione-S
      transferase activity was elevated. Intraperitonal buthionine sulfoximine
      application disclosed the inhibitory effect of fenthion on superoxide dismutase
      and glutathione peroxidase activities, whereas glutathione-S-transferase activity
      was increased. There was no change in lipid peroxidation levels during the
      experiments. No amelioration was observed in the affected parameters except the
      glutathione-S-transferase activity in the 15-day depuration period. In
      conclusion, glutathione-S-transferase and catalase enzyme activities and total
      and reduced glutathione levels were better estimators to monitor the effects of
      fenthion in low concentration in the liver of C. carpio. The depuration period
      was not adequate to recover the antioxidant capacity.

PMID- 18622871
TI  - A comparison of the therapeutic and reactivating efficacy of newly developed
      oximes (K117, K127) and currently available oximes (obidoxime, trimedoxime, HI-6)
      in tabun-poisoned rats and mice.
AB  - The potency of newly developed bispyridinium compounds (K117, K127) to reactivate
      tabun-inhibited acetylcholinesterase and reduce tabun-induced lethal toxic
      effects was compared with currently available oximes (obidoxime, trimedoxime,
      oxime HI-6) by using in vivo methods. A study that determined the percentage of
      reactivation of tabun-inhibited blood and tissue acetylcholinesterase in poisoned
      rats showed that the reactivating efficacy of newly developed oxime K127 is
      comparable with obidoxime and trimedoxime in blood but lower than the
      reactivating potency of trimedoxime and obidoxime in the diaphragm and brain. The
      potency of another newly developed K117 to reactivate tabun-inhibited
      acetylcholinesterase is comparable with obidoxime or trimedoxime in the
      diaphragm, but it is significantly lower than the reactivating potency of
      trimedoxime and obidoxime in the blood and brain. The oxime, K127, was also found
      to be relatively effective in reducing lethal toxic effects in tabun-poisoned
      mice. Its therapeutic efficacy is consistent with the therapeutic potency of
      obidoxime. On the other hand, the potency of the oxime, K117, to reduce acute
      toxicity of tabun is significantly lower compared to trimedoxime and obidoxime.
      The therapeutic efficacy of K117 and K127 corresponds to their potency to
      reactivate tabun-inhibited acetylcholinesterase, especially in the diaphragm and
      brain. Contrary to obidoxime and trimedoxime, the oxime, HI-6, is not an
      effective oxime in the reactivation of tabun-inhibited acetycholinesterase and in
      reducing the lethal effects of tabun. The reactivating and therapeutic potency of
      both newly developed oximes does not prevail over the effectiveness of currently
      available obidoxime and trimedoxime and, therefore, they are not suitable for
      their replacement of commonly used oximes for the treatment of acute tabun
      poisoning.

PMID- 18622872
TI  - Gender-related difference in the toxicity of ultraviolet absorber 2-(3',5'-di
      tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole in rats.
AB  - 2-(3',5'-Di-tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole (DBHCB) is widely
      used as an ultraviolet absorber. Previously, we showed that male rats had more
      than a 100 times higher susceptibility to the toxic effects of DBHCB than
      females. In order to investigate the role of sex steroids in the mediation of
      this gender-related difference, DBHCB (0 or 250 mg/kg/day) was given to male and
      female young intact and castrated rats by gavage for 28 days in the current
      study. In intact rats, relative liver weight increased to more than two times
      that of the control in males, while the rate of change was less than 10% in
      females. On histopathology, hypertrophy of hepatocytes was observed in males but
      not in females. In castrated rats, an approximately 40% increase in the relative
      liver weight was found only in males, and no histopathological changes in the
      liver were detected in either sex. The gender-related difference was also
      determined in preweaning rats administered DBHCB at 0, 250, or 500 mg/kg/day by
      gavage from postnatal days 4 to 21. Blood biochemical changes, including
      increases in the levels of AST, ALT, and ALP, 80-95% increase in the relative
      liver weight and histopathological changes in the liver, such as hypertrophy and
      single cell necrosis of hepatocytes, were observed at both doses in both sexes.
      In conclusion, the gender-related difference in the toxicity of DBHCB, which was
      observed in young rats, was markedly reduced by castration and abolished in
      preweaning rats.

PMID- 18622873
TI  - Repeated-dose and reproductive toxicity of the ultraviolet absorber 2-(3',5'-di-
      tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole in rats.
AB  - 2-(3',5'-Di-tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole (DBHCB) is widely
      used as an ultraviolet (UV) absorber. In this study, the repeated dose and
      reproductive toxicity of DBHCB was evaluated in rats. Crj:CD(SD)IGS rats were
      given DBHCB by gavage at 0, 2.5, 25, or 250 mg/kg/d. Male and female rats were
      dosed beginning 28 d before mating, and each female rat was mated with a male rat
      of the same dosage group. Males were dosed for a total of 56-57 d, and females
      were dosed for a total of 55-69 d up to Day 3 of lactation throughout the mating
      and pregnancy periods. Ten males from each group were killed on the next day of
      the last administration, and 10 females were killed on Days 4-6 after
      parturition. Five rats/sex treated at 0 and 250 mg/kg/d for 56 d were then kept
      without treatment for 14 d (recovery period). No deaths were found in any group.
      No effects of DBHCB on general condition, body weight, food consumption, or
      reproductive/developmental parameters were observed. Significant increases in
      serum albumin and an albumin/globulin ratio at 25 mg/kg/d and higher and alkaline
      phosphatase levels at 250 mg/kg/d were noted in males. The absolute and relative
      weights of the liver were significantly increased in males at 25 mg/kg/d and
      higher. Significantly increased serum albumin and absolute and relative liver
      weight were also found in males at 250 mg/kg/d after the recovery period. No
      changes in these parameters were observed in females of any DBHCB-treated groups.
      No significant changes in organ histopathology were found in males or females.
      These findings indicated a sex difference in the toxicity of DBHCB in rats.

PMID- 18622874
TI  - The influence of crystal habit on the prediction of dry powder inhalation
      formulation performance using the cohesive-adhesive force balance approach.
AB  - The aim of this investigation was to study the influence of crystalline habit of
      active pharmaceutical ingredients on the cohesive-adhesive force balance within
      model dry powder inhaler (DPI) formulations and the corresponding affect on DPI
      formulation performance. The cohesive-adhesive balance (CAB) approach to colloid
      probe atomic force microscopy (AFM) was employed to determine the cohesive and
      adhesive interactions of micronized budesonide particles against the {102} and
      {002} faces of budesonide single crystals and crystalline substrates of different
      sugars (cyclodextrin, lactose, trehalose, raffinose, and xylitol), respectively.
      These data were used to measure the relative level of cohesion and adhesion via
      CAB and the possible influence on in vitro performance of a carrier-based DPI
      formulation. Varying the crystal habit of the drug had a significant effect on
      the cohesive measurement of micronized budesonide probes, with the cohesive
      values on the {102} faces being approximately twice that on the {002} crystal
      faces. However, although different CAB values were measured with the sugars with
      respect to the crystal faces chosen for the cohesive-based measurement, the
      overall influence on the rank order of the CAB values was not directly
      influenced. For these data sets, the CAB gradient indicated that a decrease in
      the dominance of the adhesive forces led to a concomitant increase in fine
      particle delivery, reaching a plateau as the cohesive forces became dominant. The
      study suggested that crystal habit of the primary drug crystals influences the
      cohesive interactions and the resulting force balance measurements of colloid
      probe CAB analysis.

PMID- 18622875
TI  - Spray-dried chitosan as a direct compression tableting excipient.
AB  - The objective of this study was to prepare and evaluate a novel spray-dried
      tableting excipient using a mixture of chitosan and lactose. Three different
      grades of chitosan (low-, medium-, and high-molecular-weight) were used for this
      study. Propranolol hydrochloride was used as a model drug. A specific amount of
      chitosan (1, 1.9, and 2.5 g, respectively) was dissolved in 50 mL of an aqueous
      solution of citric acid (1%) and later mixed with 50 mL of an aqueous solution
      containing lactose (20, 19.1, and 18.5 g, respectively) and propanolol (2.2 g).
      The resultant solution was sprayed through a laboratory spray drier at 1.4
      mL/min. The granules were evaluated for bulk density, tap density, Carr index,
      particle size distribution, surface morphology, thermal properties, and tableting
      properties. Bulk density of the granules decreased from 0.16 to 0.13 g/mL when
      the granules were prepared using medium- or high-molecular-weight chitosan
      compared with the low-molecular-weight chitosan. The relative proportion of
      chitosan also showed a significant effect on the bulk density. The granules
      prepared with 1 g of low-molecular-weight chitosan showed the minimum Carr index
      (11.1%) indicating the best flow properties among all five formulations. All
      three granules prepared with 1 g chitosan, irrespective of their molecular
      weight, showed excellent flow properties. Floating tablets prepared by direct
      compression of these granules with sodium bicarbonate showed 50% drug release
      between 30 and 35 min. In conclusion, the spray-dried granules prepared with
      chitosan and lactose showed excellent flow properties and were suitable for
      tableting.

PMID- 18622876
TI  - Evaluation of arsenic trioxide-loaded albumin nanoparticles as carriers:
      preparation and antitumor efficacy.
AB  - Bovine serum albumin (BSA) nanoparticles containing arsenic trioxide (As(2)O(3))
      were prepared by a pH-coacervation method. To investigate the properties of the
      As(2)O(3)-loaded BSA nanoparticles, a study on drug-to-polymer ratio was done to
      determine the drug loading (DL), and a H-600 transmission electron microscope
      (TEM) was used to examine the particle sizes. The results showed that the DL was
      27.8% and the average particle size was about 734 nm. The drug release in vitro
      test was done, which revealed that the drug release was found to provide a slow
      release after an initial burst release and the cumulative percentage release
      reached close to 95%. In vitro cytotoxicity test was carried out using APL NB4
      cell lines (acute promyelocytic leukemia), and the anticancer efficacy in vivo
      against mouse H22 hepatoma cells was evaluated on kungming mice. The results
      indicated that the anticancer efficacy of the As(2)O(3)-loaded BSA nanoparticles
      was very obvious.

PMID- 18622877
TI  - Synthesis and evaluation of novel polyester-ibuprofen conjugates for modified
      drug release.
AB  - Ibuprofen was conjugated at different levels to a novel polyester, poly(glycerol
      adipate-co-omega-pentadecalactone) (PGA-co-PL), via an ester linkage to form a
      prodrug. The conjugates were characterized by differential scanning calorimetry
      (DSC), nuclear magnetic resonance (NMR), infrared (IR), gel permeation
      chromatography (GPC), ultraviolet (UV), and high-performance liquid
      chromatography (HPLC). The conjugates had a molecular weight between 18 and 24
      kDa, and there was a suppression of the free hydroxyl groups within the
      conjugated polymer. DSC scans showed a lowering of the melting point (T(m)) when
      compared with the polyester alone and a difference in the number and area of T(m)
      peaks. Drug release studies showed an initial burst release (13-18%) followed
      thereafter by very slow release (maximum 35% after 18 days). Continuous work may
      produce ester-linked conjugates that are sufficiently labile to allow for
      complete release of ibuprofen over the time period studied.

PMID- 18622878
TI  - Ibuprofen slow-release foam dressing reduces wound pain in painful exuding
      wounds: preliminary findings from an international real-life study.
AB  - BACKGROUND: Wound pain is a serious problem for people with chronic wounds. The
      aim of this real-life study was to compare the effect of a foam dressing that
      releases ibuprofen (Biatain Ibu) with local best practice on the treatment of
      painful exuding wounds. METHODS: A total of 185 patients with painful exuding
      wounds were randomized to either ibuprofen foam treatment (n = 98) or local best
      practice (n = 87). The primary endpoint was pain relief over 7 days of treatment,
      assessed daily using a 5-point verbal rating scale (no relief, slight relief,
      moderate relief, lots of relief, and complete relief). Secondary endpoints
      included a total reduction in pain intensity for the whole study period (using an
      11-point Numeric Box Scale: 0 = no pain to 10 = worst possible pain) and
      incidence of adverse events (AEs). RESULTS: More patients in the ibuprofen foam
      treatment group reported wound pain relief and lower wound pain intensity values
      after 7 days (p < 0.0001 for both variables). Within the four most common ulcer
      aetiolgies, patients reported significantly more effective pain relief with
      ibuprofen foam treatment (venous: p = 0.009, mixed arterial venous: p < 0.0001,
      arterial: p = 0.0009, and vasculitis: p = 0.009). In all groups, patients from
      the ibuprofen foam group reported lower pain intensities. The results were
      significant for patients with venous (p < 0.002) and arterial (p < 0.0001) leg
      ulcers. Two AEs were reported. CONCLUSIONS: The ibuprofen foam represents an
      effective and safe alternative to local best practice in the management of
      painful exuding wounds.

PMID- 18622879
TI  - Unexpected formation of 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones: synthesis,
      antibacterial and antifungal activities.
AB  - New 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones 18-22 were synthesized,
      characterized by melting point, elemental analysis, MS, FT-IR, one-dimensional
      NMR ((1)H & (13)C) spectroscopic data and evaluated for their in vitro
      antibacterial and antifungal activities. All the newly synthesized compounds
      exerted a wide range of antibacterial activities against the entire tested gram
      positive and gram-negative bacterial strains except Escherichia coli. Compounds
      21 and 22 exerted strong antifungal activities against Aspergillus flavus, mucor
      and Microsporum gypsuem. In addition, compound 20 was more potent against
      Rhizopus.

PMID- 18622880
TI  - Ethnicity as a variable in mental health research: a systematic review of
      articles published 1990-2004.
AB  - The objective of the study was to investigate how the ethnic variable has been
      used in mental health research, in theory, in measurement and classification
      criteria. Journal articles published 1990-2004 that address original research on
      psychopathology, treatment and mental health services and with "ethnic" or
      "ethnicity" in their title or abstract were selected. The papers were examined
      for their theoretical definition of ethnicity, how the ethnic data were collected
      and the criteria used to identify ethnic groups. The use of comparison groups and
      country of the studies were recorded. A total of 421 papers were identified. An
      explicit theoretical definition was found in 33 (7.8%) papers. Data collection
      procedure was mentioned in 248 (58.9%) and 104 (24.7%) papers described how data
      was converted into ethnic groups. The operationalizations of ethnicity have
      remained almost unchanged during the 15-year review period. Generally, the ethnic
      variable was incompletely reported. Confusion regarding which individual or
      social characteristics ethnicity refers to makes the research findings of limited
      value in clinical settings, and may continue to create misunderstanding about the
      effect of ethnicity in clinical contexts.

PMID- 18622881
TI  - Treating panic symptoms within everyday clinical settings: the feasibility of a
      group cognitive behavioural intervention.
AB  - Panic disorder is a common and debilitating disorder that has a prevalence rate
      of 3-5% in the general population. Cognitive-behavioural interventions have been
      shown to be an efficacious treatment for panic, although a limited number of
      studies have examined the effectiveness of such interventions implemented in
      everyday clinical settings. The aim of the following pilot study was to examine
      the feasibility of a brief group cognitive-behavioural intervention carried out
      in a clinical setting. Salient issues in determining feasibility include:
      representativeness of patient group treated, amount of significant clinical
      change displayed and resources required to carry out the intervention. A small
      sample of GP-referred patients displaying panic symptoms completed a 2-week
      intensive cognitive-behavioural intervention. Results collected post-intervention
      revealed significant clinical reductions in panic, anxiety and depressive
      symptoms and marked improvement in mobility. These improvements were maintained
      at 12-month follow-up. Outcomes supported the feasibility of a brief group
      cognitive-behavioural intervention for GP-referred patients. Implications of
      these results are discussed in terms of implementing effective treatments in
      everyday clinical practice and developing a stepped care approach to treating
      panic symptoms.

PMID- 18622882
TI  - Long-term sickness absence and disability pension with psychiatric diagnoses: a
      population-based cohort study.
AB  - Sickness absence certified with psychiatric diagnoses is increasing in many
      Western countries. A substantial proportion of the sickness absentees never
      return to work, but ends up with a permanent disability pension (DP). This study
      investigated the incidence of long-term sickness absence (LTSA) with different
      psychiatric diagnoses, and tested predictors of the transition to permanent DP. A
      special objective was to explore previously reported gender differences, using a
      population-based cohort study. The population at risk of LTSA was 106,674
      occupational active men and 89,356 women in a Norwegian county in 1994; 314 women
      and 203 men with LTSA >8 weeks, certified with a psychiatric diagnosis, were
      followed to the end of 1999, with DP as the endpoint. Diagnoses on sickness
      certificates, age, gender and income were used as explanatory variables in Cox
      regression analysis. Annual incidence of LTSA with a psychiatric diagnosis was
      7.0/1000/year for women and 3.8/1000 for men; 72% of the women and 50% of the men
      had a diagnosis indicating depression. During follow-up, 32% of the men and 25%
      of the women obtained DP. Increasing age, male gender, low income and a diagnosis
      of psychosis or "other" increased the DP risk. Separate analysis for men
      indicated a different effect of age and a larger role of serious mental illness.
      The study verified that women more often than men had LTSA with psychiatric
      diagnoses, especially with depression. Men were at higher risk of transition to
      DP, and the study suggested some possible explanations.

PMID- 18622883
TI  - Attitudes towards mental disorders--still lots of work to do.

PMID- 18622884
TI  - Mental health of Bosnian refugee children: a comparison of clinician appraisal
      with parent, child and teacher reports.
AB  - This study compares clinician appraisal of Bosnian refugee children with
      independent parent, child and teacher reports. From whom and by what means can
      children "at risk" be reasonably identified? Forty-eight Bosnian refugee children
      (aged 7-20), resettled in Sweden 1994-95, were assessed clinically by means of a
      semi-structured interview. Thereafter, standardized mental health questionnaires
      were administered to parents (Achenbach's Child Behavior Checklist), children
      (Achenbach's Youth Self-Report and Macksoud's Posttraumatic Stress Reaction
      Checklist) and teachers (clinician designed School Competence Scale and
      Achenbach's Teacher's Report Form). On clinician interview, nearly half of the
      children (48%) were identified with one or more mental health problem "demanding
      further attention". Depressiveness was the single most prevalent symptom (31%);
      followed by post-traumatic stress (23%), and anxiety-regressiveness (15%). At the
      same time, 75% of the children were rated by teachers as "quite competent" in
      school. Parent, child and clinician appraisals of primary school children showed
      broad similarities. Teachers reported a similar prevalence of child distress, but
      identified different symptoms and different children demanding attention.
      Evaluation of teenage youths showed greater disparity: teenagers labeled their
      own symptoms more often as post-traumatic stress reactions and teachers
      identified few youths in need of attention. Inter-relatedness among parent, child
      and clinician appraisals supports the robustness of our semi-structured
      interview. At the same time, apartness of teacher report underscores the need to
      incorporate an outside-world vantage point in the process of risk assessment.
      Also, a more concrete presentation of post-traumatic stress reactions and a
      higher "further attention" threshold for inward emotional problems seem called
      for.

PMID- 18622885
TI  - Implementation of a rational pharmacotherapy intervention for inpatients at a
      psychiatric department.
AB  - The objective of the study was to develop, implement and evaluate two treatment
      algorithms for schizophrenia and depression at a psychiatric hospital department.
      The treatment algorithms were based on available literature and developed in
      collaboration between psychiatrists, clinical pharmacologists and a clinical
      pharmacist. The treatment algorithms were introduced at a meeting for all
      psychiatrists, reinforced by the project psychiatrists in the daily routine and
      used for educational purposes of young doctors and medical students. A
      quantitative pre-post evaluation was conducted using data from medical charts,
      and qualitative information was collected by interviews. In general, no
      significant differences were found when comparing outcomes from 104 charts from
      the baseline period with 96 charts from the post-intervention period. Most of the
      patients (65% in the post-intervention period) admitted during the data
      collection periods did not receive any medication changes. Of the patients
      undergoing medication changes in the post-intervention period, 56% followed the
      algorithms, and 70% of the patients admitted to the psychiatric hospital
      department for the first time had their medications changed according to the
      algorithms. All of the 10 interviewed doctors found the algorithms useful. The
      treatment algorithms were successfully implemented with a high degree of
      satisfaction among the interviewed doctors. The majority of patients admitted to
      the psychiatric hospital department for the first time had their medications
      changed according to the algorithms.

PMID- 18622886
TI  - Similarity and binding in memory: bound to be detrimental.
AB  - The process of binding information from different modalities and sources into an
      object is ubiquitous in cognition and has been a problem for research and
      modelling efforts in psychology. This process has been considered by most
      researchers as necessarily always beneficial to memory. In the present study we
      provide evidence that binding can be detrimental through the propagation of
      vulnerabilities to interference. Phonologically similar and dissimilar letters
      were presented sequentially at different locations on a computer monitor.
      Participants had to recall either the letters in their order of presentation or
      the spatial locations at which the letters had appeared. Whether binding was
      encouraged or not--providing prior knowledge of which dimension to remember-
      phonological similarity had a detrimental effect on recall of locations. Such a
      finding poses a challenge to the view that binding is the panacea in enhancing
      memory capacity.

PMID- 18622887
TI  - Passive perceptual learning in relation to wine: short-term recognition and
      verbal description.
AB  - This experiment addressed the question of whether untutored experience of
      drinking wine improves human ability to discriminate between wines. Using a short
      term recognition task a two-factor design compared more with less experienced
      wine drinkers (intermediates vs. novices) and a condition requiring description
      of the to-be-remembered wine samples with a control condition. Overall
      intermediates were more accurate than novices in selecting the target sample from
      a distractor set. The procedure was modelled on a previous study in which verbal
      descriptions reduced the performance of intermediates (verbal overshadowing), but
      here both novices and intermediates performed better in the description than in
      the control condition. The major result was to demonstrate that untutored
      experience can improve wine recognition (passive perceptual learning).

PMID- 18622888
TI  - Microstructural analysis of ingestive behaviour reveals no contribution of
      palatability to the incomplete extinction of a conditioned taste aversion.
AB  - An analysis of the microstructure of licking responses was used to investigate
      the effects of conditioning and extinguishing a taste aversion. Rats received a
      single pairing of 8% fructose with lithium chloride (LiCl) while controls
      received unpaired exposure to fructose and LiCl. Pairing fructose with LiCl
      produced a reduction both in consumption and in the size of licking clusters.
      Subsequent exposure to fructose in the absence of LiCl produced some extinction
      of the taste aversion although at asymptote there was a residual difference in
      consumption between the taste aversion group and unpaired controls. In contrast
      the reduction in lick cluster size did completely extinguish. Previous analyses
      of licking microstructure indicate that lick cluster size is related to the
      palatability of the ingested solution. Thus these results indicate that although
      taste aversion learning initially reduces the palatability of the cue solution
      this reduction is not permanent. These results are discussed with reference to
      the possibility that preparatory behaviours are more resistant to extinction than
      are consummatory behaviours.

PMID- 18622889
TI  - Heparin-induced Extracorporal LDL precipitation (H.E.L.P) in diabetic foot
      syndrome - preventive and regenerative potential?
AB  - Peripheral arterial disease is more aggressive in concomitant diabetes posing an
      increased risk for critical limb ischemia and subsequent limb loss. The majority
      of therapies available are not effective to prevent amputation in patients with
      severe disease. The current observational study reports the effect of the heparin
      induced extracorporal LDL-precipitation (H.E.L.P.) as a novel therapeutic
      approach in patients with severe diabetic foot syndrome. Seventeen diabetic
      patients with septic foot lesions recruited from the diabetic outpatient clinic
      underwent H.E.L.P. apheresis regularly until fibrinogen levels were stabilized at
      3 g/l or infection was controllable as evidenced by alleviation of necrosis.
      Patients were subsequently followed up for 2 to 73 months. Fibrinogen levels were
      reduced by 68% after H.E.L.P. treatment. No severe complications were noted.
      Necrosis could be confined in sixteen patients. Minor amputations were indicated
      in twelve patients. Three patients underwent major amputations of the lower limb
      and two patients received surgical reconstruction. In conclusion, H.E.L.P.
      apheresis may offer an alternative therapeutic option to diabetic patients with
      critically ischemic feet and appears to have a beneficial major/minor amputation
      ratio.

PMID- 18622890
TI  - Effects of leptin on lipid metabolism.

PMID- 18622891
TI  - The European perspective of diabetes prevention.
AB  - The dramatic increase in newly diagnosed cases of type 2 diabetes is a major
      public health concern within the European Union. However, it has been
      demonstrated that prevention programmes can significantly reduce the risk of
      developing diabetes. There is a clear consensus amongst healthcare professionals
      that action is urgently needed at both EU and community levels. The challenge is
      to implement proven intervention methods effectively into clinical reality. To
      achieve this, action is needed not only in the field of policy development but
      also in the development of targeted intervention programmes, which address the
      needs of people with an increased diabetes risk, clinical- and community-based
      healthcare professionals, and the general population. The Diabetes Prevention
      Forum (DPF), founded by the European region of the International Diabetes
      Federation, consists of European diabetes experts from a range of backgrounds.
      The DPF is taking immediate action to co-ordinate and improve the information
      flow between all relevant stakeholders to enable more effective communication, so
      helping to improve the ability to prevent type 2 diabetes in Europe.

PMID- 18622892
TI  - Statin suppresses apoptosis in osteoblastic cells: role of transforming growth
      factor-beta-Smad3 pathway.
AB  - Statins possess pleiotropic effects in several tissues. Among them, their bone
      anabolic actions have been recently noted. We have proposed that Smad3, a TGF
      beta-signaling molecule, is a promoter of bone formation. However, whether
      statins would affect TGF-beta-Smad3 pathway in osteoblasts is still unknown. The
      present study was performed to examine the effects of statin on Smad3 expression
      and cell apoptosis by employing mouse osteoblastic MC3T3-E1 and rat osteoblastic
      UMR-106 cells. Statins (pitavastatin, mevastatin, and simvastatin) as well as
      alendronate increased the levels of Smad3 in MC3T3-E1 cells. The effects of
      pitavastatin on Smad3 levels were observed from 3 hours and later. Pitavastatin
      induced the expression of TGF-beta, and cycloheximide, a protein synthesis
      inhibitor, antagonized the increased levels of pitavastatin on Smad3. On the
      other hand, pitavastatin antagonized dexamethasone- or etoposide-induced
      apoptosis in a dose-dependent manner, and Smad3 inactivation by dominant negative
      Smad3 or an inhibition of endogenous TGF-beta action by SB431542 antagonized anti
      apoptotic effects of pitavastatin, indicating that pitavastatin suppressed
      osteoblast apoptosis partly through TGF-beta-Smad3 pathway. In conclusion, the
      present study has demonstrated for the first time that statin suppressed cell
      apoptosis partly through TGF-beta-Smad3 pathway in osteoblastic cells.

PMID- 18622893
TI  - Reduced frequency of peripheral plasmacytoid dendritic cells in type 1 diabetes.
AB  - Dendritic cells (DCs) as antigen presenting cells play an important role in the
      initiation of an autoimmune disease like type 1 diabetes. Although there is
      evidence from the NOD mouse model that the function and frequency of DCs is
      altered in type 1 diabetes, there is little data on dendritic cells in human type
      1 diabetes. We investigated peripheral blood myeloid (mDC1 and mDC2) and
      plasmacytoid dendritic cells (pDCs) in 15 type 1 diabetes patients with recent
      onset (within the last 3 months) of type 1 diabetes as well as in 15 patients
      with long standing (more than 5 years) type 1 diabetes by flow cytometry. Both
      groups were compared to age matched controls. We observed a significantly reduced
      percentage of pDCs of peripheral blood mononuclear cells (PBMCs) in both recent
      onset (0.13 vs. 0.25%, p=0.01) and long standing type 1 diabetes patients (0.13
      vs. 0.24%, p=0.01). The absolute counts of pDCs per ml of blood were also
      significantly lower in both recent onset (mean 9560 vs. 13524, p=0.048) and long
      standing diabetes (mean 7869 vs. 12202; p=0.05). The percentage of mDC1 was
      significantly diminished in recent onset (0.21% vs. 0.30%, p=0.034), but not in
      long standing type 1 diabetes. Our study demonstrates a persisting reduction of
      peripheral plasmacytoid DCs in type 1 diabetes patients. Since pDCs are involved
      in the control of immune responses and inducing regulatory cells, a reduced
      number of pDCs may predispose to an autoimmune reaction in the pancreatic islets.

PMID- 18622894
TI  - Expression and mutation analysis of the tyrosine kinase c-kit in poorly
      differentiated and anaplastic thyroid carcinoma.
AB  - Poorly differentiated and anaplastic thyroid carcinoma are aggressive tumors
      failing to res-pond to conventional therapy. Imatinib mesylate offers an
      effective therapeutic option in patients with various types of malignancies by
      inhibiting tyrosine kinases such as c-kit. In this study we investigated c-kit
      expression in anaplastic and poorly differentiated thyroid carcinoma compared to
      differentiated carcinoma and adenoma and the presence of c-kit mutations. In
      total, 224 thyroid tissues were analyzed by immunohistochemistry. Mutation
      analysis of exon 9, 11, 13, and 17 of the c-kit gene was performed in anaplastic
      and poorly differentiated carcinoma. c-Kit expression was negative in all
      anaplastic thyroid carcinoma, while c-kit expression of poorly differentiated
      carcinoma showed a high variability with a more intense staining in tumors
      showing obvious differentiated malignant follicular tumor areas. Differentiated
      carcinoma showed a slight, but not significantly stronger c-kit expression than
      poorly differentiated carcinoma. All tumors revealed wild type sequences of c-kit
      gene in exons 9, 11, 13, and 17. The low or lacking c-kit expression in
      undifferentiated thyroid carcinoma together with the lack of mutations argue
      against a crucial role of c-kit in thyroid carcinoma cell proliferation. Further
      molecular targets of imatinib mesylate have to be analyzed to estimate a
      potential benefit of this drug for patients with dedifferentiated thyroid
      carcinoma.

PMID- 18622895
TI  - Effect of olive oil consumption on serum resistin concentrations in healthy men.
AB  - Resistin has been linked to atherosclerosis and inflammatory processes in humans.
      Some polyphenols have been shown to downregulate resistin expression in
      adipocytes. The effects of olive oil phenolics on resistin are not known;
      therefore, we investigated the impact of olive oil consumption on serum resistin
      as a function of the olive oils' phenolic content. In a randomized, controlled,
      cross-over study 38 healthy German men aged 38+/-2 years replaced their usual
      consumption of raw fat during 3 periods of 3 weeks each by 25 ml of virgin,
      common and refined olive oil varying in phenolic content. Serum resistin, blood
      lipids and urine biomarkers of subjects' compliance were analysed at baseline and
      at the end of each intervention period. The integration of olive oil in the
      subjects' habitual diet led to a decrease in total cholesterol (p=0.025) and
      triglycerides (p=0.013) independent of the content of phenolic compounds in the
      oil. Serum resistin concentrations were not affected by the olive oils' phenolic
      content. After low phenolic olive oil consumption, a decrease in serum resistin
      level was observed compared to medium and high phenolic olive oil (-0.4+/-0.1
      ng/ml; p=0.040). Our results suggest that olive oil consumption has only marginal
      beneficial effects on serum resistin levels.

PMID- 18622896
TI  - Relation of plasma obestatin levels to bmi, gender, age and insulin.
AB  - Obestatin is supposed to be involved in nutrient homeostasis. Therefore, basal
      plasma obestatin levels were investigated in 321 normal weight and obese subjects
      in relation to body mass index, gender, age, insulin concentrations, and type 2
      diabetes mellitus. Additionally, postprandial obestatin levels were determined in
      20 normal weight subjects. Basal obestatin levels in females were higher compared
      to males (193.6+/-5.8 vs. 140.6+/-5.1 pg/ml). Obestatin levels correlated
      inversely and significantly with body mass index (f: r=-0.632, p<0.001; m: r=
      0.487, p<0.001) and basal insulin levels (f: r=-0.536, p<0.001; m: r=-0.320,
      p=0.008) in females and males. However, in a multiple regression analysis as well
      as in a matched comparison of a low and high insulin group no significant
      relationship between insulin and obestatin levels was observed in nondiabetics.
      On the other hand, inclusion of type 2 diabetics with higher insulin levels
      resulted in a significant inverse correlation. Obestatin levels were independent
      of age in both sexes. In patients with type 2 diabetes mellitus basal obestatin
      levels were not different compared to nondiabetic subjects when matched for
      gender, body mass index, and insulin. In normal weight subjects, postprandial
      obestatin levels showed a significant decrease between 60 and 90 minutes rising
      to basal levels thereafter. The present data demonstrate a relation of plasma
      obestatin levels to body weight, gender and food intake, but not to age. The
      inverse relationship with insulin might depend on the level of hyperinsulinemia.
      The present data are compatible with a potential role of obestatin in nutrient
      regulation.

PMID- 18622897
TI  - Abdominal adipose tissue: early metabolic dysfunction associated to insulin
      resistance and oxidative stress induced by an unbalanced diet.
AB  - The possible contribution of early changes in lipid composition, function, and
      antioxidant status of abdominal adipose tissue (AAT) induced by a fructose-rich
      diet (FRD) to the development of insulin resistance (IR) and oxidative stress
      (OS) was studied. Wistar rats were fed with a commercial diet with (FRD) or
      without 10% fructose in the drinking water for 3 weeks. The glucose (G),
      triglyceride (TG), and insulin (I) plasma levels, and the activity of antioxidant
      enzymes, lyposoluble antioxidants, total glutathione (GSH), lipid peroxidation as
      TBARS, fatty acid (FA) composition of AAT-TG as well as their release by
      incubated pieces of AAT were measured. Rats fed with a FRD have significantly
      higher plasma levels of G, TG, and I. Their AAT showed a marked increase in
      content and ratios of saturated to monounsaturated and polyunsaturated FAs,
      TBARS, and catalase, GSH-transferase and GSH-reductase, together with a decrease
      in superoxide dismutase and GSH-peroxidase activity, and total GSH, alpha
      tocopherol, beta-carotene and lycopene content. Incubated AAT from FRD released
      in vitro higher amount of free fatty acids (FFAs) with higher ratios of saturated
      to monounsaturated and polyunsaturated FAs. Our data suggest that FRD induced an
      early prooxidative state and metabolic dysfunction in AAT that would favor the
      overall development of IR and OS and further development of pancreatic beta-cell
      failure; therefore, its early control would represent an appropriate strategy to
      prevent alterations such as the development of type 2 diabetes.

PMID- 18622898
TI  - Competent sonography brings a diagnostic odyssey to an end--a case of seldom
      genesis of ascites.

PMID- 18622899
TI  - Astragaloside IV inhibits proliferation and promotes apoptosis in rat vascular
      smooth muscle cells under high glucose concentration in vitro.
AB  - Astragaloside IV is one of the main active ingredients of Radix astragali, which
      is a herbal remedy widely used in traditional Chinese medicine for the treatment
      of diabetes and cardiovascular diseases. However, its effects on vascular smooth
      muscle cell (VSMC), which plays a key role in the development of diabetic
      vascular complications, were not well studied. The present study was performed to
      examine the effects of astragaloside IV on proliferation, apoptosis and
      phenotypic modulation of VSMC under high D-glucose (25 mM). Application of
      astragaloside IV inhibited the proliferation and the rise of the proliferation
      index (PI) of VSMC induced by high glucose in a dose-dependent manner.
      Astragaloside IV induced apoptosis in VSMC under high glucose conditions,
      accompanied with typical morphological alterations and loss of mitochondrial
      membrane potential (Delta Psim). In addition, Western blot analysis revealed that
      astragaloside IV increased the expression of alpha-smooth muscle actin, an
      important phenotypic modulation marker. In conclusion, astragaloside IV could
      inhibit high glucose-induced VSMC proliferation through intervention with the
      cell cycle, promoting apoptosis and regulating phenotypic modulation of VSMC,
      which strongly suggest that astragaloside IV could hinder the process of
      pathological vascular remodeling in diabetic patients.

PMID- 18622900
TI  - Triterpenoid saponins from Androsace umbellata and their anti-proliferative
      activities in human hepatoma cells.
AB  - Two new triterpenoid saponins, along with five known ones, were isolated from the
      EtOH extract of the whole plants of Androsace umbellata. The structures of the
      new triterpenoid saponins were identified as 3- O-[ beta- D-xylopyranosyl-(1-->2)
      beta- D-glucopyranosyl-(1-->4)-[ beta- D-glucopyranosyl-(1-->2)]- alpha- L
      arabinopyranosyl]-3 beta-hydroxy-13 beta,28-epoxy-16-oxo-oleanan-30-al ( 1) and 3
      O- beta- D-xylopyranosyl-(1-->2)- beta- D-glucopyranosyl-(1-->4)- alpha- L
      arabinopyranosyl-3 beta-hydroxy-13 beta,28-epoxy-16-oxo-oleanan-30-al ( 2) on the
      basis of their spectral and chemical properties. All these compounds showed
      significant cytotoxic activities in human hepatoma cells.

PMID- 18622901
TI  - A study on artifacts formation in the Thai traditional medicine Prasaplai.
AB  - The artificial formation of three fatty acid esters, ( E)-4-(3,4
      dimethoxyphenyl)but-3-en-1-yl linoleate ( 1), ( E)-4-(3,4-dimethoxyphenyl)but-3
      en-1-yl oleate ( 2) and ( E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl palmitate ( 3)
      originating during storage by the interaction of components in Prasaplai
      preparation was investigated. The artifacts were not formed when 0.1 mL of water
      or more was added to 1.0 g of the mixture (1 : 1) of Zingiber cassumunar and
      Nigella sativa even when stored for 20 days. This result showed that water was
      able to stop the esterification reaction. The formation of the artifacts by
      chemical reaction under water-free conditions was evaluated. ( E)-4-(3,4
      dimethoxyphenyl)but-3-en-1-ol was mixed with linoleic acid in the presence of
      anhydrous Na (2)SO (4) and stored in a dessicator for 7 days. The artifact ( 1)
      was formed in 6.0 % yield. It was concluded that a water-free environment is
      necessary for the direct chemical formation of the artificial esters.

PMID- 18622902
TI  - Converging effects of Ginkgo biloba extract at the level of transmitter release,
      NMDA and sodium currents and dendritic spikes.
AB  - In this study, an attempt was made to integrate the effects of GINKGO BILOBA
      extract (GBE) in different experimental systems (IN VITRO cochlea, brain slice
      preparations and cortical cell culture) to elucidate whether these processes
      converge to promote neuroprotection or interfere with normal neural function. GBE
      increased the release of dopamine in the cochlea. NMDA-evoked currents were dose
      dependently inhibited by rapid GBE application in cultured cortical cells. GBE
      moderately inhibited Na+ channels at depolarised holding potential in cortical
      cells. These inhibitory effects by GBE may sufficiently contribute to the
      prevention of excitotoxic damage in neurons. However, these channels also
      interact with memory formation at the cellular level. The lack of effect by GBE
      on dendritic spike initiation in neocortical layer 5 pyramidal neurons indicates
      that the integrative functions may remain intact during the inhibitory actions of
      GBE.

PMID- 18622903
TI  - Growth inhibition and apoptosis induction by tanshinone IIA in human colon
      adenocarcinoma cells.
AB  - Tanshinone IIA is the most abundant diterpene quinone in Danshen, Salviae
      miltiorrhizae Radix, a widely prescribed traditional herbal medicine that is used
      to treat cardiovascular and inflammatory diseases. Recently, tanshinone IIA was
      demonstrated to induce cell death and apoptosis in a variety of tumors. However,
      the effect of tanshinone IIA on human colon cancer cells is not clearly
      understood yet. In this study, the antigrowth and apoptosis-eliciting effects of
      tanshinone IIA, as well as its cellular mechanisms of actions, were investigated
      in Colo-205 human colon cancer cells. Tanshinone IIA reduced cell growth in a
      concentration-dependent manner, inducing apoptosis accompanied by an increase in
      TUNEL staining and by an increased percentage of cells in the sub-G1 fraction.
      The expression of p53 and p21 and mitochondrial cytochrome c release were
      increased in tanshinone IIA-treated cells. In addition, the expression of Fas
      proteins was up-regulated by tanshinone IIA. Tanshinone IIA-induced catalytic
      activation of caspases was confirmed by cleavage of caspase-8 and caspase-3.
      These findings suggest that tanshinone IIA induces apoptosis in Colo-205 cells
      through both mitochondrial-mediated intrinsic and Fas-mediated extrinsic caspase
      cell-death pathways. Accordingly, the chemotherapeutic potential of tanshinone
      IIA for colon cancer warrants further study.

PMID- 18622904
TI  - Bacillus subtilis FZB24 affects flower quantity and quality of saffron (Crocus
      sativus).
AB  - The effect of Bacillus subtilis FZB24 on saffron ( Crocus sativus L.) was studied
      using saffron corms from Spain and the powdered form of B. SUBTILIS FZB24(R).
      Corms were soaked in water or in B. subtilis FZB24 spore solution for 15 min
      before sowing. Some corms were further soil drenched with the spore solution 6,
      10 or 14 weeks after sowing. Growth and saffron stigma chemical composition were
      measured. Compared to untreated controls, application of B. subtilis FZB24
      significantly increased leaf length, flowers per corm, weight of the first flower
      stigma, total stigma biomass; microbe addition also significantly decreased the
      time required for corms to sprout and the number of shoot sprouts. Compared to
      the controls, picrocrocin, crocetin and safranal compounds were significantly
      increased when the plants were soil drenched with the spore solution 14 weeks
      after sowing; in contrast crocin was highest in untreated controls. Results of
      this study suggest that application of B. subtilis FZB24 may provide some benefit
      to saffron growers by speeding corm growth (earlier shoot emergence) and
      increasing stigma biomass yield by 12 %. While some treatment conditions also
      increased saffron chemical composition, these were generally not the same
      treatments that simultaneously improved growth yields and thus, more study is
      required.

PMID- 18622906
TI  - Cucurbitane-type triterpene glycosides from the fruits of Momordica charantia.
AB  - Phytochemical investigation of the fruits of Momordica charantia resulted in the
      isolation and characterization of two new (1 and 2) and eight known cucurbitane
      type triterpene glycosides and one cucurbitane-type triterpene. The glycosides
      (7beta,25-dimethoxycucurbita-5(6),23( E)-dien-19-al 3- O-beta-D-allopyranoside
      (1); 25-methoxycucurbita-5(6),23(E)-dien-19-ol 3-O-beta-D-allopyranoside (2);
      momordicosides A, F (1), F (2), G, K, and L; and goyaglycoside-c and
      goyaglycoside-d) and the triterpene [3 beta,7 beta,25-trihydroxycucurbita-5,23(E)
      dien-19-al] were characterized by physical, chemical, and spectroscopic
      techniques, including 1D- and 2D-NMR as well as by comparison with the reported
      data.

PMID- 18622905
TI  - 1,2,3,4,6-penta-O-galloyl-beta-D-glucose from Galla Rhois protects primary rat
      hepatocytes from necrosis and apoptosis.
AB  - In this study, we investigated the hepatoprotective effects of four compounds
      from Galla Rhois [gallic acid methyl ester, gallic acid, an equilibrium mixture
      of 3-galloyl-gallic acid and 4-galloyl-gallic acid isomers, and 1,2,3,4,6-penta-
      O-galloyl- beta- D-glucose (PGG)] in primary rat hepatocytes undergoing necrosis
      or apoptosis. Treatment with gallic acid methyl ester (12.5 and 50 microM) or PGG
      (3.125, 12.5 and 50 microM) reduced hepatocyte necrosis induced by tert-butyl
      hydroperoxide. PGG treatment (4 and 20 microM) also altered hepatocyte apoptosis
      induced by glycochenodeoxycholic acid. Based on these results, we propose that
      PGG warrants further evaluation as a hepatoprotective agent, because it protected
      primary rat hepatocytes from both necrosis and apoptosis.

PMID- 18622907
TI  - Speciation analysis, bioavailability and risk assessment of copper complexes in
      phytomedicines using flame atomic absorption spectrometry.
AB  - Octanol (n-C8H17OH), the configuration of which resembles a carbohydrate and
      lipid, was used as a biomembrane model, and an octanol-water system was adopted
      to study the distribution of copper in herbal decoctions under the acidity of
      saliva, gastric juice, bile and intestinal fluid. Octanol- and water-solubility
      were used for speciation analysis and the bioavailability assessment of copper.
      The influence of a combination of Aconitum carmichaeli and Paeonia lactiflora at
      different ratios, the acidity of the digestive site on the species, and the
      bioavailability and dose of copper were studied. The concentrations of copper in
      the original herbal materials and in N-octanol- and water-soluble fractions were
      determined by flame atomic absorption spectrometry following mixed acid
      digestion. The results showed that the digestive juice acidity, phytomedical
      composition, and combination ratio of phytomedicines dominated both the species
      present and the bioavailability of copper. The concentration of octanol-soluble
      copper could be used to represent the bioavailability assessment of copper in the
      phytomedicines, and the dosage of copper in the phytomedicines could be designed
      based on the level of the octanol-soluble copper and the recommended dietary
      allowance for copper (0.9 mg/day). Risk assessment could be examined through
      comparison of the level of octanol-soluble copper and the tolerable upper intake
      level for copper (10 mg /day).

PMID- 18622908
TI  - (-)-Xanthienopyran, a new inhibitor of superoxide anion generation by activated
      neutrophils, and further constituents of the seeds of Xanthium strumarium.
AB  - The dried seeds of XANTHIUM STRUMARIUM (Asteraceae) are used after thorough stir
      frying as an ingredient in traditional Chinese medicines for relieving allergy.
      Two new compounds, xanthialdehyde ( 2) and (-)-xanthienopyran ( 7), as well as 26
      known compounds were isolated in the present study. The structures of the
      isolates were elucidated by spectroscopic methods. Among them, compound 7
      exhibited significant selective inhibition of superoxide anion generation by
      human neutrophils induced by formyl- L-methionyl- L-leucyl- L-phenylalanine, with
      an IC50 value of 1.72 microg/mL.

PMID- 18622909
TI  - [Imaging of breast tissues changes--early detection, screening and problem
      solving].
AB  - In the industrialised countries breast cancer is the cancer with the highest
      prevalence and causes the highest rate of cancer deaths among women. In
      Switzerland alone, about 5000 newly diagnosed cases occur per year. Our three
      main diagnostic tools in imaging diseases of the breast in the setting of
      screening, early detection or problem solving are mammography, ultrasound and MRI
      with intravenous contrast application. The most important imaging technique is
      mammography, which as only method has shown evidence to be suitable for screening
      so far. As a major accomplishing imaging tool there is sonography, which in women
      under 30 years of age is the first method of choice in examination of the
      breasts. The MRI is able to provide additional information about the perfusion of
      tissue changes within the breast; because of its low specificity, however, it
      should cautiously be applied for specific questions.

PMID- 18622911
TI  - [Adjuvant!Online--an Internet-based decision tool for adjuvant chemotherapy in
      early breast cancer].
AB  - Adjuvant chemotherapy dramatically improves prognosis for early breast cancer.
      Large, international randomized studies with thousands of patients not only
      introduced new effective drugs, but also led towards more individualized
      treatment strategies based on a number of prognostic factors. The integration,
      however, of the growing amount of information from clinical trials into every-day
      decision-making becomes an increasingly difficult task. Adjuvant!Online is an
      open-access computer program (www.adjuvantonline.com). From the entries of
      patient information and tumour characteristics the program calculates a
      prognostic estimate of outcome in terms of relapse and survival with and without
      adjuvant chemotherapy. This article focuses on the advantages and pitfalls in
      using Adjuvant!Online for informed treatment decisions in early breast cancer.

PMID- 18622910
TI  - [Adjuvant endocrine therapy in breast cancer].
AB  - Tamoxifen is the standard treatment in premenopausal hormone-receptor positive
      breast cancer patients with additional benefit in some of these women by adding
      ovarian ablation or suppression. Actual trials are investigating the use of more
      complete estradiol suppression with an LHRH agonist in combination with an
      aromatase inhibitor (TEXT, SOFT and ABCSG 12 trial) in premenopausal patients.
      Outside clinical trials this treatment may be considered in special cases when
      tamoxifen is contraindicated. In the majority of postmenopausal women the optimal
      adjuvant hormonal therapy includes the use of an aromatase inhibitor. However the
      best use of these agents, either as initial therapy or after treatment with
      tamoxifen has still to be answered. Again the optimal duration of endocrine
      therapy remains still open. Extended adjuvant therapy with an AI after completion
      of five years tamoxifen is especially in node positive patients a reasonable
      option. However if extension of endocrine therapy with an AI after five years of
      an AI-containing regimen is also beneficial is currently investigated in several
      clinical trials. In selected postmenopausal patients with hormone-receptor
      positive disease the use of five years of tamoxifen can still be a viable option.

PMID- 18622913
TI  - [Adjuvant radiotherapy in breast cancer].
AB  - During the last decades the treatment of breast cancer has changed considerably.
      Radical surgical procedures have increasingly been replaced by breast conserving
      therapy including radiation therapy of the whole breast (WBI). This change in
      treatment approach is partly due to clinical study results and pathological
      observations. The current indications and guidelines in the treatment of breast
      cancer by radiation are shown along with the ensuing implications for patient and
      physician. More recently, growing interest has been noted in partial breast
      irradiation. The different techniques for partial breast irradiation (APBI),
      their advantages and drawbacks are outlined.

PMID- 18622912
TI  - [New treatment approaches in breast cancer].
AB  - A great step was taken in the treatment of the prognostically unfavourable group
      of Her2-positive breast cancer in the past years with the introduction of the
      targeted therapy with trastuzumab, which showed significant increase in median
      survival in the metastatic and adjuvant setting of Her2-positive breast cancer
      patients. Lapatinib, an oral HER2-tyrosine kinase inhibitor, showed activity in
      patients with breast cancer progression after trastuzumab. The role of lapatinib
      in the adjuvant setting will be examined in the ongoing, multicenter,
      prospective, four-arm ALTTO-trial, which compares the current standard treatment
      of one year trastuzumab against lapatinib, the combination of trastuzumab and
      lapatinib and an arm with sequential trastuzumab followed by lapatinib. Another
      promising treatment option is the VEGF-antibody bevacizumab, which blocks tumor
      mediated angiogenesis leading to oxygen undersupply and finally growth inhibition
      of the tumor. Concerning treatment decision, two ongoing prospective trials in
      the USA and Europe are eagerly awaited, which examine the role of gene-array
      assessment in terms of risk stratification and finally tailoring adequate
      treatment.

PMID- 18622914
TI  - [Use of trastuzumab in the therapy of breast cancer].
AB  - Trastuzumab (Herceptin) is a humanized monoclonal antibody recognizing the human
      epidermal growth factor receptor-2 (HER-2/neu). This receptor is overexpressed in
      20-30% of invasive breast carcinomas. HER-2/neu normally regulates cell growth
      and survival, and overexpression leads to increased signaling and thus to
      malignant transformation and growth. HER-2/neu overexpression used to confer a
      worse prognosis, as these tumors respond poorly to a variety of chemo- and
      hormonal therapies. The invention of targeted therapies against the HER-2/neu
      receptor changed this picture. Trastuzumab binds to HER-2/neu close to the cell
      membrane and inhibits signal transduction, as well as leading to receptor
      degradation and immune-mediated attack against the tumor cells. It was shown to
      be effective and safe in several clinical trials, and approved for use in humans.
      The most important adverse effect is cardiotoxicity, leading to a risk of
      congestive heart failure in some patients, especially those pretreated with
      anthracyclines. As this risk is low, adjuvant trastuzumab therapy was
      investigated and showed very positive results. The addition of trastuzumab to
      adjuvant chemotherapy consistently resulted in significant increases of both
      disease-free and overall survival. Therefore, trastuzumab should nowadays be
      applied to all eligible patients, i.e. patients whose tumor over-expresses HER
      2/neu with a immunostaining intensity of 3+ or shows HER-2/neu gene amplification
      as demonstrated by fluorescence in situ hybridization (FISH), and who do not have
      other contraindications. This article highlights the results of pertinent
      clinical trials and discusses current knowledge on the optimal use of
      trastuzumab.

PMID- 18622915
TI  - [Pregnancy-associated breast cancer].
AB  - Pregnancy-associated breast cancer is a rare disease with an incidence of 1:3000.
      There is no indication anymore to terminate the pregnancy since the maternal
      prognosis will not be influenced. Due to physiologic pregnancy-related changes in
      the breast, the interpretation of clinical findings, breast ultrasound and
      mammography is more demanding. There is often a diagnostic delay in detecting
      pregnancy-associated breast cancer. Mastectomy and axillary lymphonodectomy
      compose the surgical therapy. In the third trimester, breast conserving surgery
      and radiotherapy postpartum is an option. Chemotherapy can be administered
      relatively safe in the second and third trimester. Radiotherapy, hormonal therapy
      and trastuzumab are contraindicated during pregnancy. Patients with pregnancy
      associated breast cancer should be seen and treated in an interdisciplinary
      setting, preferably in a specialized centre.

PMID- 18622916
TI  - [Hormone replacement therapy in peri- and postmenopausal women and breast cancer
      risk].
AB  - Hormone therapy (HT), in peri- and postmenopause has been associated with a
      modest increase in the risk of breast cancer. Hormones play a major role in
      tumorigenesis of breast cancer, and reproductive factors are known to influence
      breast cancer risk. Female sex steroids are used for contraception or menopause
      treatment by women of reproductive age and postmenopausal women respectively.
      This review reports recent published epidemiological evidence and randomised
      trials which examined the effect of HT on the risk of breast cancer.

PMID- 18622917
TI  - [Genetic counseling in familial breast cancer].
AB  - It is currently estimated that 25-30% of all breast cancers have a familial
      background. The breast cancer lifetime risk of first degree relatives with a
      family history of breast cancer may be classified as slightly, moderately or
      highly increased above the population risk. Individuals from families with a
      highly increased risk for breast cancer should be offered genetic counselling and
      testing. Here, the elements of genetic counselling and testing and the management
      of families with a highly increased breast and ovarian risk will be discussed.

PMID- 18622918
TI  - [Clinical ethics consultation - an integrative model for practice and
      reflection].
AB  - Broad evidence exists that health care professionals are facing ethical
      difficulties in patient care demanding a spectrum of useful ethics support
      services. Clinical ethics consultation is one of these forms of ethics support
      being effective in the acute setting. An authentic case is presented as an
      illustration. We introduce an integrative model covering the activities being
      characteristic for ethics consultation and going beyond "school"-specific
      approaches. Finally, we formulate some do's and don'ts of ethics consultation
      that are considered to be key issues for successful practice.

PMID- 18622919
TI  - [Judgement and informed consent].
AB  - Every diagnostic or therapeutic medical intervention requires a legal basis. This
      is in most cases informed consent. The ability to give informed consent depends
      on correct judgement which can be influenced by many mental disorders, therefore
      doctors have to check the mental state of a patient before they accept his or her
      consent.

PMID- 18622920
TI  - [Physical and sexual violence against adult persons - forensic aspects in the
      daily medical work].
AB  - Physical and sexual violence is an increasing issue in daily clinical praxis. The
      article defines the different kinds of violence like domestic violence, urban
      violence, accidental and self-inflicted injuries. Medical Doctors should be
      teached in forensic thinking and acting regarding victims of any kind of
      violence, especially concerning the disclosure of no accidental injuries and the
      importance of a complete and standardized forensic documentation.

PMID- 18622921
TI  - [Physical and sexual child abuse].
AB  - Child abuse may result in dramatic short and longtime damage of children's
      physical and emotional well being. This underscores the clinician's special
      responsibility to contribute a sound professional and scientific approach to the
      multiprofessional diagnosis and intervention in suspected child abuse cases. The
      approach is to correlate the probability of a given finding with the history and
      comparing it to biomechanical principles. Of concern are especially all serious
      injuries with an alleged trivial or inadequate for age mechanism, missing, vague
      or changing patterns of explanation, injuries of different age, delay of medical
      care and allegations by independent observers or even the child. Exact
      documentation of all medical examinations is the basis of any forensic expertise
      if child abuse is to be considered. This paper ist dealing with morhological
      findings following various kinds of violence which can often be observed in
      connection with child abuse, as well as the interpretation of characteristic
      patterns of findings. Furthermore, practicable procedures after diagnosing child
      abuse ar being discussed on the basis of legal terms.

PMID- 18622922
TI  - [Reproach of malpractice - legal procedure and possible consequences].
AB  - Legal liability proceedings against doctors have increased considerably within
      the last few years. These discussions frequently start with communication
      problems between doctors and patients. Patients should be informed openly about
      unwanted incidents; this does not mean recognition of a liability obligation.
      Many proceedings do not get to courts when an agreement can be obtained after an
      independent expertise. In addition to a criminal proceeding a civil law liability
      can follow on proved malpractice. The important steps of legal proceeding and
      their consequences are represented.

PMID- 18622923
TI  - [Examination of fitness to drive].
AB  - Driving a car in public traffic requires a high performance that is often
      underestimated owing to daily habit. Fitness to drive can be impaired temporary
      or permanently because of taking substances declining the performance and because
      of various somatic diseases and psychic disorders. To check the fitness to drive
      is the responsibility of medical examination in terms of road traffic. This is
      supposed to be an individual examination corresponding to acknowledged guidelines
      by an experienced expert in order to keep away dangerous drivers from road
      traffic but not to reduce excessively the personal freedom of those drivers, who
      do not endanger road traffic considerably.

PMID- 18622924
TI  - [The extraordinary death].
AB  - The examination of a deceased person is an important duty for physicians. It
      comprises the certification of death, the certification of the identity of the
      deceased, a thorough examination of the body, an estimation of the moment of
      death and ends with the decision, if death was caused by a certain or possible
      violent cause in which case it must be reported to the authorities. Problems and
      pitfalls are discussed on the basis of practical case presentations.

PMID- 18622925
TI  - [Sudden death in infancy].
AB  - In industrial countries, sudden infant death syndrome (SIDS) poses the most
      common mode of deaths occurring in the postneonatal period. During the last years
      the incidence has decreased and is currently less than 0.5 per 1000 live births.
      The cause of SIDS is still unknown. One theory claims that SIDS is due to
      suffocation caused by failure of central respiratory control, CO(2) rebreathing
      or airways obstruction. Further pathological factors including hyperthermia as
      well as impairment of the sleeping- and waking centre are in discussion. The most
      important risk factors include lying prone, heat exposure of the child, premature
      delivery, maternal age less than 18 years, smoking and drug abuse during
      pregnancy and the absence of breast feeding. SIDS is not an entity but a
      descriptive term for sudden and unexpected deaths in infancy without adequate
      cause of death being established by methods currently used. SIDS in forensic
      medicine is not only important because of its relative frequency, but also
      because of the differential diagnoses which have to be considered in each case.
      Therefore other natural and unnatural causes of death have to be explored by
      autopsy and careful postmortal examination (histological, toxicological,
      microbiological and virological analysis), taking into account circumstances at
      the death scene and medical history of the infant.

PMID- 18622926
TI  - [Medical end-of-life decisions and assisted suicide].
AB  - Medical end-of-life decisions that potentially shorten life (Sterbehilfe) are
      normally divided into four categories: Passive Sterbehilfe refers to withholding
      or withdrawing life-prolonging measures, indirect Sterbehilfe refers to the use
      of agents such as opioids or sedatives to alleviate symptoms of a terminally ill
      patient, assisted suicide (Suizidbeihilfe or Beihilfe zum Suizid) refers to
      prescribing and/or supplying a lethal drug in order to help someone to end his
      own life, and active euthanasia - which is illegal in any circumstances - means a
      doctor actively ending a patients life. In passive and indirect euthanasia, the
      will of a competent patient, or the presumed will of an incompetent patient
      respectively, is crucial. Assisted suicide is not illegal according to the Swiss
      Penal Code as long as there are no motives of self-interest of the individual
      assisting, and the individual assisted has decisional capacity. However, for
      doctors participating in assisted suicide, specific requirements of medical due
      care have to be met. What this means in the context of assisted suicide has
      recently been elaborated by the Swiss Federal Court of Justice.

PMID- 18622927
TI  - [Polyarteritis Nodosa, a vanishing vasculitis since its main cause has been
      identified].
AB  - The polyarteritis nodosa is a vasculitis for which the main cause had been
      identified as hepatitis B, a chronic infectious disease inducing an overshooting
      immune reaction. Thanks to this discovery, the treatment of polyarteritis nodosa
      has changed from a symptomatic immunosuppressive therapy to a treatment strategy
      focusing on the disease inducing infectious agent. Vaccination against hepatitis
      B- virus has been instrumental in the reduction of the prevalence of
      polyarteritis nodosa. In case of the rare entity of polyarteritis nodosa without
      hepatitis B, only a symptomatic immunosuppressive therapy can be prescribed. The
      history of polyarteritis nodosa clearly illustrates that future research in the
      field of so called autoimmune diseases should focus on the causes rather than on
      the immunologic effector mechanisms and/or the symptomatic immunosuppressive
      therapy.

PMID- 18622928
TI  - [Cryoglobulinemia].
AB  - Cryoglobulins are immunoglobulins that precipitate at temperatures below 37
      degrees C. They mainly occur in association with hepatitis C but also in other
      persistent viral infections and autoimmune as well as hematologic diseases. As
      circulating immune-complexes, they can cause severe tissue damage in virtually
      all organs, in particular the skin, joints and kidneys. This article gives a
      review on the different types of cryoglobulinemia, their clinical presentation
      and current therapeutic strategies.

PMID- 18622929
TI  - [Cerebral vasculitis].
AB  - Cerebral vasculitis is a rare disease with a potentially harmful or even fatal
      outcome that often affects young adults. Primary autoimmune mediated disease can
      be distinguished from secondary vasculitis associated to infectious disorders,
      connective tissue diseases, malignancies or toxic drug effects. Pathomechanisms
      lead to destruction of the vessel wall and consecutive hemorrhagic or ischemic
      brain lesions. Beyond these mechanisms direct autoimmune mediated neurotoxicity
      is postulated. Clinical presentation is highly variable with potentially
      fluctuating signs and symptoms. Besides multifocal deficits from disseminated CNS
      involvement, diffuse encephalopathy or psychosis may result from diffuse CNS
      affection. For systemic vasculitis with CNS involvement, affection of joints,
      skin and organs may facilitate the diagnostic evaluation. CNS affection in
      systemic diseases is highly variable and may even precede systemic manifestation.
      The diagnostic work-up includes clinical evaluation, analysis of autoantibodies,
      MRI, digital subtraction angiography and biopsy of the affected tissue in
      doubtful cases. Standard therapy are corticosteroids often combined with
      immunosuppressants such as azathioprine, methotrexate or mycophenolate mofetil in
      chronic disease or cyclophosphamid in acute disorder. When therapy can be
      initiated timely, prognosis of cerebral vasculitis is usually favourable.

PMID- 18622930
TI  - [Retroperitoneal fibrosis, M. Ormond, periaoartitis, ...?].
AB  - Retroperitoneal fibrosis or Morbus Ormond is a rare disease characterized by
      inflammatory fibrosis of the retroperitoneal space and the abdominal aorta often
      including the common iliac arteries. The abdominal aorta can be enlarged leading
      to a classification of retroperitoneal fibrosis with or without aneurysm of the
      abdominal aorta. The classic form of retroperitoneal fibrosis usually presents
      without aneurysm of the abdominal aorta. Clinical presentation is not specific
      and includes abdominal, flank or back pain. Mechanisms, initiating factors and
      pathophysiology of the disease have remained unclear to date, however there is
      evidence that autoimmune mechanisms are involved. The most relevant complication
      of retroperitoneal fibrosis is the involvement of the ureter leading to
      obstructive nephropathy and requiring relief from obstruction. Because of the low
      frequency of the disease associated with a great variety of presentation no
      randomized controlled trials are available. Drug therapy is limited to steroids
      alone or in combination with immunosuppressive drugs such as azathioprine or even
      cyclophosphamide. The response to medical therapy is variable from patient to
      patient. Clinical endpoints are general symptoms, sedimentation rate, and imaging
      studies with abdomen CT or MRI.

PMID- 18622931
TI  - [Childhood Henoch-Schonlein syndrome--common and uncommon features,
      complications, Finkelstein-Seidlmayer variant and management].
AB  - Although Henoch-Schonlein syndrome can occur at any age, it is overwhelmingly a
      disease of childhood. Indeed, Henoch-Schonlein syndrome is the most common
      vasculitis that affects children. The clinical features of this vasculitis are
      well documented, and the diagnosis is generally not difficult. This article
      briefly reviews both common and uncommon clinical aspects of the condition and
      information concerning therapy. A further focus of this review is recent
      information concerning abnormalities of immunoglobulin IgA1 glycosylation and the
      role of aberrantly glycosylated immunoglobulins in the development of Henoch
      Schonlein syndrome. The final focus of the article is acute hemorrhagic edema, a
      benign vasculitis limited to the skin, which is characterized by circinate,
      medallion-like purpura, and ecchymoses and occurs in children younger than 4
      years of age. The nosologic position of acute hemorrhagic edema, which has also
      been called Finkelstein-Seidlmayer syndrome, as a variant of Henoch-Schonlein
      syndrome is the subject of considerable debate, but most authors agree that there
      are sufficient clinical and prognostic differences to consider it a separate
      entity.

PMID- 18622932
TI  - [Sjogren's syndrome].
AB  - The leading symptoms of this autoimmune disease are xerostomia and xerophthalmia.
      Both are characterised by a lymphoplasmacellular destructive inflammation of
      salivary and lacrimal glands and the detection of autoantibodies against Ro/SS-A
      and La/SS-B nuclear antigens. In the long run of the disease, a polyclonal
      hypergammaglobulinemia is evolving as a consequence of chronic B-cell stimulation
      which can also lead to B-cell lymphoma which underlines the need for periodical
      clinical and laboratory examinations. Further extraglandular manifestations of
      the disease are non-erosive polyarthritis, serositis, leukocytoclastic cutaneous
      vasculitis and polyneuropathy, which make a clear differentiation from different
      forms of autoimmune connectivitis even more difficult, in particular if sicca
      syndrome is also present which may represent a secondary Sjogren's syndrome. The
      treatment is mostly symptomatic and immunosuppressive drugs are only given in
      case of severe and life-threatening organ involvement.

PMID- 18622933
TI  - [Systemic sclerosis].
AB  - Systemic sclerosis (scleroderma) is characterized by autoimmune phenomena and a
      progressive fibrosis. Clinical signs include Raynaud's phenomenon, pathognomonic
      nail fold capillary changes, pulmonal, renal, cardial and intestinal involvement.
      The two forms of systemic sclerosis, the diffuse and the limited show distinct
      disease phenomena and evolution. The diffuse form typically leads to a rapid
      sclerosis of the whole skin, it is associated with the auto-antibody Scl-70, it
      presents with an interstitial fibrosis of the lung, myositis and cardial
      fibrosis, a progressive loss of intestinal motility with maldigestion and it
      bears the risk of renal crisis. The limited form is characterized by sclerosis of
      the skin of the distal parts of the limbs and the face only, it is associated
      with the centromer auto-antibody and a much slower progression of visceral
      fibrosis. A typical late stage manifestation is pulmonary arterial hypertension.
      New drugs have improved quality of life. Their correct indication is based on a
      systematic monitoring of disease.

PMID- 18622934
TI  - [Pulmonary vasculitis].
AB  - Following an international consensus conference held in Chapel Hill, North
      Carolina, USA, vasculitides have been divided based on the size of the vessel
      involved in the inflammatory process. Thus, the terms large, medium and small
      vessel vasculitis emerged. Wegener's granulomatosis, microscopic polyangitis and
      Churg-Strauss syndrome are described as small vessel vasculitides. Pulmonary
      involvement is a characteristic feature of both Wegener's granulomatosis and
      Churg-Strauss syndrome, less so in microscopic polyangitis. A pathognomonic
      feature is alveolar haemorrhage, which encompasses the trias: 1) bilateral acinar
      pulmonary infiltrates reminiscent of pulmonary edema, 2) anemia and 3)
      haemoptysis, which however may be absent. Bronchoalveolar lavage typically
      returns lavage fluid that remains hemorrhagic even after sequential sampling. The
      discovery that antineutrophil cytoplasmic antibodies (ANCA) are strongly
      associated with vasculitic disorders and their subsequent characterisation has
      led to improved understanding of the pathogenic mechanisms underlying vasculitis.
      This paper will review clinical aspects of pulmonary involvement in the systemic
      vasculitides.

PMID- 18622935
TI  - [Systemic ANCA-associated vasculitis--diagnosis and therapy].
AB  - ANCA-associated vasculitis represents a group of small-vessel vasculitides,
      including Wegener's granulomatosis, microscopic polyangiitis and the Churg
      Strauss-syndrome. These diseases affect mainly small arteries, venules and
      capillaries, showing a lack of immunocomplex formation on immunohistology, the so
      called "pauci-immune" vasculitis. Nevertheless, Anti-Neutrophil Cytoplasmatic
      Autoantibodies (ANCA's) are pathogenic for this type of disease. In spite of
      important advances in technical diagnostic tools, careful medical history and
      clinical examinations often give the clues for the correct diagnosis. Recent
      collaborative therapeutic studies have lead to therapeutic schemas that are much
      more adapted to the individual disease state. Besides the acute and sometimes
      life-threatening form of ANCA-vasculitis, chronic disease and relapses become
      more important in clinical practice. Thus, therapeutic efficacy must be
      outweighed against long-term toxicity to make the right choice for therapeutic
      intervention in ANCA-associated vasculitis.

PMID- 18622936
TI  - [Safety and efficacy of biologics directed against TNF-alpha and CD20 in the
      therapy of vasculitis and systemic lupus erythematosus].
AB  - While the inhibition of TNF-alpha has been shown to improve vasculitis in vitro
      and in animal models, the clinical evidence for the efficacy of TNF-alpha
      blockade in most forms of vasculitis is mainly based on case reports and case
      series. Randomised controlled studies have so far not shown superiority of anti
      TNF-alpha agents for Wegener's granulomatosis and giant cell arteritis. Moreover,
      in the context of Wegener's granulomatosis, a higher frequency and severity of
      infections are to be expected. In refractory cases of Behcet's disease therapy of
      uveitis and other organ manifestations is promising. Rituximab has achieved good
      effects in case reports of vasculitis. Results from controlled trials are not
      available. Observational studies indicate that in refractory systemic lupus
      erythematosus, and possibly also in several instances of small vessel vasculitis,
      rituximab can achieve good responses. The increased frequency of severe
      infections under TNF-alpha blockade requires a stringent benefit and risk
      assessment in addition to a multidisciplinary analysis of follow-up parameters. A
      detailed information of the patient regarding symptoms and signs of a possible
      infection are a prerequisite. Due to the complexity of the field and the danger
      of morbidity and mortality as a consequence of vasculitis or systemic lupus
      erythematosus on the one hand, and of the therapy on the other, biologics should
      only be used to treat these disorders in institutions fully equipped and staffed
      for this purpose.

PMID- 18622937
TI  - [Comment on the European guidelines for use of delayed action drugs for treatment
      of hyperkinetic disorders].

PMID- 18622938
TI  - [Long-acting medications for the treatment of hyperkinetic disorders - a
      systematic review and European treatment guideline. Part 1: overview and
      recommendations].
AB  - A panel of experts from several European countries has accomplished a systematic
      review of published and unpublished data on the use of long-acting medications in
      ADHD and hyperkinetic disorder. Based on this analysis detailed recommendations
      about the use of these drugs in practice have been developed: (1) Long-acting
      preparations should be licensed and used; (2) They should not completely replace
      short-acting drugs (which will be the initial treatment for many children in view
      of cost and the greater flexibility of dosing). Individual clinical choices are
      necessary. (3) Both ATX and extended-release stimulants should be available. In
      addition, detailed recommendations will be made with regard to the criteria to be
      applied in choosing a preparation for the individual patient.

PMID- 18622939
TI  - [Long-acting medications for the treatment of hyperkinetic disorders - a
      systematic review and European treatment guidelines. Part 2: a quantitative
      evaluation of long-acting medications].
AB  - A panel of experts from several European countries has accomplished a systematic
      review of published and unpublished data on the use of long-acting medications in
      ADHD and hyperkinetic disorders, on the basis of which practical recommendations
      for the application of these medications have been developed. The current article
      outlines results of this analysis, comparing the effect sizes and numbers-needed
      to-treat for extended-release stimulant preparations and atomoxetine (ATX). It is
      concluded (1) that long-acting preparations should be licensed and used. (2)
      However, they should not completely replace short-acting medications, in view of
      costs as well as the greater flexibility of dosing. Individual choices of therapy
      are necessary. (3) Both ATX and retarded-release stimulants should be available.

PMID- 18622940
TI  - [The treatment of Attention-Deficit/Hyperactivity Disorders with polyunsaturated
      fatty acids - an effective treatment alternative?].
AB  - OBJECTIVES: Both omega-3 and omega-6 long-chain polyunsaturated fatty acids
      (PUFA) have a substantial impact on human brain development and function.
      However, in western industrial countries omega-3 LC-PUFA in particular are often
      lacking in diets. Increasing evidence indicates that LC-PUFA imbalance or
      deficiencies may be associated with Attention Deficit/Hyperactivity Disorder
      (ADHD) through involvement in the dopaminergic corico-striatal metabolism.
      Preliminary study result suggest that dietary supplementation with LC-PUFA might
      be effective in the treatment of ADHD. METHODS: This review summarizes the
      knowledge in terms of a hypothesized pathogenetic relationship between fatty acid
      metabolism and ADHD and discusses the possible clinical benefit of a primary or
      combined treatment with LC-PUFA. RESULTS: Actually it is unclear whether a
      deficit in intake or metabolism of LC-PUFA may play a major role in the
      pathogenesis of ADHD. Moreover treatment studies yielded conflicting results. A
      combination of Omega-3 and Omega-6 - fatty acids might attenuate the symptoms of
      ADHD significantly, thus making this dietary intake useful. CONCLUSIONS:
      Considerable research has to be done in the future to identify ideal therapeutic
      combinations and dosages of various fatty acids, and to develop reliable ways of
      defining those individuals to benefit from this treatment access.

PMID- 18622941
TI  - [Diagnostic of personality disorders in adolescence according to SCID-II].
AB  - OBJECTIVES: The aim of the present study was to ascertain whether the Structured
      Clinical Interview for DSM-IV Personality Disorders (SCID-II) is applicable for
      use with adolescents. Furthermore, the diagnostic concordance between SCID-II and
      the clinicians' estimations of personality disorders (PD) is assessed. In
      addition, we identified predicting factors for personality disorders in
      adolescent psychiatric inpatients. METHODS: 110 adolescent psychiatric inpatients
      aged 14-18 years were assessed by means of SCID-II and a personality and disorder
      inventory (PSSI). RESULTS: 32.7% of the inpatients met the criteria for PD
      according to SCID-II. While agreement between the presence of any PD based on
      SCID-II and that found according to clinicians' estimations was low, moderate and
      very good agreement between SCID-II and clinicians' estimations was found with
      regard to borderline PD and histrionic PD. Logistic regression analyses
      identified "anorexia nervosa (binge-purging)", "attention-deficit/hyperactivity
      disorder/conduct disorder (ADHD/CD)" and "socioeconomic status" as good
      predictors for PD. CONCLUSIONS: The SCID-II - which was primarily developed for
      use with adults - is suitable for use among adolescents. Anorexia nervosa (binge
      purging type) and ADHD/CD are closely associated with the development of PD in
      adolescents.

PMID- 18622942
TI  - [The care of mentally retarded children and adolescents with psychiatric
      disorders in hospitals for child and adolescent psychiatry and psychotherapy in
      Germany - results of a questionnaire survey].
AB  - OBJECTIVES: To assess the prevalence of and standards of treatment for young
      mentally retarded patients in inpatient units and ambulant settings. METHODS:
      Mail questionnaire survey of all German hospitals for child and adolescent
      psychiatry (N = 136); 68 closed-ended questions; 54.4% respondents. RESULTS: The
      average prevalence was 6% of in- and outpatients. Specialised inpatient units for
      the mentally retarded are available at 8% of the hospitals; 5% only have
      outpatient services, i.e., most of the clients are managed within mainstream
      units. The standards of assessment and treatment are as usual. Pharmacotherapy is
      not more frequent. The quality of services is more or less sufficient. Of the
      responders, 85% demand specialised in- and outpatient psychiatric services for
      the mentally retarded in every federal state. CONCLUSIONS: The overall deficit of
      psychiatric services for mentally retarded children and adolescents in Germany is
      confirmed. New specialised in- and outpatient services must be created in every
      federal state. The quality of assessment and treatment seems to be sufficient to
      establish accurate diagnoses and multidisciplinary therapeutic approaches.

PMID- 18622945
TI  - Vitamin C, vitamin B12, folate and the risk of osteoporotic fractures. A case
      control study.
AB  - Water-soluble vitamins influence the development of an adequate structure of bone
      tissue, but there is scant information relating them with osteoporotic fractures.
      We analyze whether serum vitamin C, vitamin B12, and erythrocyte folate, or
      dietary intake of vitamin C and folate, are related with osteoporotic fractures
      in the elderly. A hospital-based case-control study was carried out at the
      Hospital of Jaen (167 cases, 167 controls), Spain. Cases were defined as patients
      aged 65 or more years with a low-energy fracture. Controls were people without
      fracture, matched for age and sex with cases. Diet was assessed by a semi
      quantitative food frequency questionnaire. Serum vitamin C was measured using
      high-performance liquid chromatography (HPLC). Folic acid and vitamin B12 were
      measured using procedures of competitive or immunometric immunoassay.
      Multivariable analyses were also fitted to adjust for confounding using analysis
      of covariance (for the comparison of adjusted means) and conditional logistic
      regression (for estimating adjusted odds ratios). A statistically significant
      difference between cases and controls for vitamin C blood levels was found, being
      higher for controls (p = 0.01). Analysis of the association between serum vitamin
      C and fracture risk showed a linear trend (p = 0.03) with a significantly reduced
      risk for the upper quartile (OR = 0.31; 95% CI 0.11-0.87). The intake of vitamin
      C, folic acid, and B12 was not related to fracture risk, nor was there any
      association with erythrocyte folate or serum vitamin B12. In conclusion, serum
      vitamin C levels were lower in cases with osteoporotic fractures than in
      controls.

PMID- 18622946
TI  - Isolation and structural elucidation of different geometrical isomers of
      lycopene.
AB  - Five geometrical isomers of lycopene were isolated from a photoisomerized mixture
      on a semi-preparative C30 column and characterized by UV-vis spectroscopy, mass
      spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. 1H NMR and 2D
      NMR measurements were used to unambiguously assign the double bond configuration
      of five isomers: (5Z,9'Z)-, (9Z)-, (5Z,9Z)-, (all-E)-, and (5Z)-lycopene. This
      will allow other laboratories to use the results for their C30 HPLC. In addition,
      it is possible to investigate structure-activity relationships for these lycopene
      isomers which will improve the understanding of their physiological role in
      biological tissues.

PMID- 18622947
TI  - Relationship between nutrient intake and vitamin D status in osteoporotic women.
AB  - Vitamin D is essential for maintaining calcium homeostasis and optimizing bone
      health. Its inadequacy is related to many factors including dietary intake. The
      aim of the present study was to evaluate serum 25(OH)D and its relationship with
      nutrient intakes in postmenopausal Brazilian women with osteoporosis. This cross
      sectional study comprised 45 free-living and assisted elderly at Sao Paulo
      Hospital. Three-day dietary records were used to assess dietary intakes. Bone
      mineral density was measured with a dual-energy X-ray absorptiometer (DXA). Blood
      and urine sample were collected for analysis of biochemical markers of bone and
      mineral metabolism. Insufficiency of vitamin D was observed in 24.4% of the women
      and optimal levels (> or = 50 nmol/L) were observed in 75.6%. Parathyroid hormone
      was above the reference range in 51% of the participants. The mean calcium (724
      mg/day) and vitamin D (4.2 microg/day) intakes were lower than the value proposed
      by The Food and Nutrition Board and sodium intake was more than two-fold above
      the recommendation. Higher levels of serum 25(OH)D were inversely associated with
      sodium intake. Dietary strategies to improve serum vitamin D must focus on
      increasing vitamin D intake and should take a reduction of sodium intake into
      consideration.

PMID- 18622948
TI  - Levels of fat-soluble micronutrients and 2,6-cyclolycopene-1,5-diol in head and
      neck cancer patients.
AB  - Smoking negatively affects serum carotenoid levels, and it is a negative
      prognostic factor for head and neck cancer. In this study, micronutrient levels
      were examined in 60 smoking and non-smoking head and neck cancer patients. The
      goal was to determine if oxidation of the carotenoid lycopene would occur to a
      greater extent in smokers. Subjects were drawn from a prospective cohort study
      and matched on seven demographic factors. Serum levels of alpha-carotene,
      zeaxanthin, and 2,6-cyclolycopene-1,5-diol A, an oxidation product of lycopene,
      were all lower in smokers versus non-smokers (18%, 22%, and 8%, respectively)
      while beta-carotene, beta-cryptoxanthin, and lutein were about the same in the
      two groups. Levels of lycopene, gamma-tocopherol, and alpha-tocopherol were
      higher in smokers, and notably serum alpha-tocopherol was 48% higher in smokers.
      The majority of vitamin E intake was from supplements. The higher levels of alpha
      tocopherol in smokers were interesting in that higher alpha-tocopherol levels
      have been associated with higher mortality in head and neck cancer. Although this
      was a pilot investigation, there was no evidence that 2,6-cyclolycopene-1,5-diol
      A formation was appreciably affected by smoking status, but alpha-tocopherol
      levels were higher in smokers.

PMID- 18622949
TI  - Habitual tea drinking and bone mineral density in postmenopausal Turkish women:
      investigation of prevalence of postmenopausal osteoporosis in Turkey (IPPOT
      Study).
AB  - AIM: In this epidemiological report, we assessed the prevalence of osteopenia and
      osteoporosis (OP) in postmenopausal Turkish women and the relationship between
      body mass index (BMI), and some nutritional factors (habitual tea, coffee,
      tobacco, and milk product consumption) with OP. METHODS: This multicenter study
      was done in postmenopausal women residing in five big cities, in four different
      regions of Turkey between August and November 2005. An inclusion criterion was
      being in the postmenopausal period for at least 12 months. A semi-structured
      questionnaire was completed by face-to-face interview, consisting of closed- and
      open-ended questions about demographic characteristics, nutritional status, and
      habits with two or more choices as possible responses. Bone mineral density (BMD)
      measurements were performed with a MetriScan Densitometer (Alara Inc., CA, USA).
      RESULTS: Seven hundred twenty-four women were included in the study. The mean age
      was 57.6 +/- 9.6 years, and mean age at natural menopause was 46.4 +/- 5.6 years.
      Of the participants, 51% were illiterate. According to WHO classification; 42.5%
      were normal in terms of BMD, 27.2% had osteopenia, and 30.2% had OP. Women with
      high education levels had better T-scores (p = 0.019). Increase in BMI also had a
      positive effect on T-scores (p < 0.0001). A linear correlation was found between
      age (r= -0.386, p < 0.0001), BMI (r = -0.175, p < 0.0001), and education (r = 
      0.317, p < 0.0001), with T-scores. The T-scores of women who consumed tea on a
      regular basis were found to be higher than non-consumers (-1.51 +/- 1.68 vs. 
      1.09 +/- 1.66; p = 0.070) [when smokers, those who received hormonal therapy
      (HT), and those > 65 years were excluded]. CONCLUSION: OP was determined in 1/3
      of the women. Advanced age (> 65) and being illiterate were negative factors,
      while high education levels, being overweight, and being treated with HT had a
      positive effects on BMD. Habitual tea drinking also may have a positive effect on
      BMD. However, tea drinking was not found to be a statistically significant factor
      in the present study.

PMID- 18622950
TI  - Dietary intake of carotenoid isomers in Israel.
AB  - Controversy exists regarding the possible protective role of carotenoids against
      cancer. Evidence is mainly against all-E-beta-carotene, while there is no
      evidence against other carotenoids or against mixtures of beta-carotene
      stereoisomers. Carotenoid isomers could account for the variability in study
      results but are rarely estimated, and reference to the degree of their
      consumption is lacking. The aim of our study was to create a comprehensive
      database of carotenoid isomers content in food items commonly consumed in Israel.
      Food items were analyzed using a liquid chromatography system to determine the
      content of carotenoid isomers in Israeli food. The main sources of carotenoids
      detected in Israeli foods were tomato juice, tomato, watermelon, parsley,
      coriander, spinach, carrot, sweet potato, banana, zucchini, mango, loquat,
      pepper, eggplant, and chickpeas. Data were used to measure consumption in healthy
      participants of a case-control study, using a semi-quantitative food-frequency
      187-item questionnaire. Compared to reference studies, the median carotenoid
      isomers intake in 712 Israeli healthy controls (age range 23-95 years, mean 71 +/
      10.9 years, median 73 years) was higher for beta-carotene, alpha-carotene, beta
      cryptoxanthin, and zeaxanthin, while the intake of lycopene was lower. Major
      differences in consumption were noticed between ethnic groups consuming
      Mediterranean diets and those consuming Western-type diets. Population
      consumption patterns of carotenoid isomers using a comprehensive database are
      used to improve our understanding in disease prevention. Consumption in Israel
      seems to be generally higher than that reported in studies conducted elsewhere,
      and varies by ethnic group.

PMID- 18622951
TI  - Body composition in an adult population in southern Spain: influence of lifestyle
      factors.
AB  - The aim of the present study was to assess the body composition in an adult
      Mediterranean population by two methods, to identify groups at risk for obesity
      and lifestyle factors that might influence this risk. A cross-sectional study was
      carried out in Andalusia, a western Mediterranean region in southern Spain. Body
      composition was studied with anthropometric methods and bioelectric impedance
      analysis (BIA) in a random sample of 394 subjects (169 men, 225 women) between 20
      and 60 years of age. When anthropometric methods were used, we found that 19.4%
      of the individuals had a body mass index (BMI) > or = 30 kg/m(2). In 46.2% of the
      men, more than 25% of the body weight consisted of fat, and in 74.1% of the
      women, more than 30% of the body weight consisted of fat. When BIA data were
      used, these values rose to 34.7% and 60.6% for men and women respectively. After
      controlling for sex, age correlated directly with percentage of body fat when
      skinfold thickness (r = 0.58) or BIA (r = 0.40) was used. In smokers, the number
      of cigarettes/day correlated directly with waist circumference (r = 0.76), after
      controlling for both age and sex. We found high percentages of obesity regardless
      of the indicator or method used, particularly in women. Factors such as sex, age,
      leisure-time physical exercise, educational level, and smoking appeared to
      influence obesity. The factors that made the greatest contribution to the rates
      of obesity and high waist-hip ratio were the age, time spent exercising, and
      educational level. In contrast, the risk of high body fat (as determined with
      both methods) was associated only with sex and age.

PMID- 18622953
TI  - [Tumor surveillance after resection of lung cancer].
AB  - The idea of follow-up visits in lung cancer patients treated in a curative intent
      is on one side early detection and management of treatment related complications
      and on the other side a long term surveillance program for early detection of new
      primary lung cancers or recurrences of the primary lung cancer allowing curative
      (re)-treatment. The first is best performed by the specialists (thoracic
      surgeons, oncologists, radiotherapists) and the intervals of the follow-up visits
      are 3-6 months. In this phase adjuvant therapies as well as a specific
      surveillance program should be determined. Smoking cessation is strongly
      recommended and an adequate support should be offered. Patients treated in a
      curative intent and who are in an adequate performance status should be seen in
      six months intervals in the first three years and thereafter annually by
      assessing the medical history, physical exam and for applying imaging modalities
      such as chest X-ray or CT-Scan of the chest and upper abdomen. The patient should
      be instructed to detect symptoms and react accordingly. Positron Emission
      Tomography, sputum cytology, tumor markers and blood tests as well as
      fluorescence bronchoscopy are not recommended for routine follow-up except in
      controlled randomized trial protocol. These statements are based on guidelines
      from several societies as well as from a literature research.

PMID- 18622954
TI  - [Follow-up recommendations for patients after curative treatment of invasive
      breast cancer].
AB  - Oncologic follow-up and surveillance after curative therapy for invasive breast
      cancer serves as a quality control of the primary treatment results, enables the
      early diagnosis and immediate treatment in case of recurrent disease, the
      detection and therapy of treatment-related side effects and late sequelae, and
      finally includes the psychologic support of tumor-free patients over decades,
      during which they are at risk for recurrent disease.

PMID- 18622955
TI  - [Diagnosis, treatment and follow up of prostata cancer].
AB  - Prostate cancer is the most frequent diagnosed malignancy in men with an
      increasing incidence. In well informed men between the age of 50 and 70 years
      screening should be offered when requested. Not every newly diagnosed prostate
      cancer requires immediate treatment. Curative treatment should be offered to men
      with a minimal life expectancy of 10 years. In men older than 50-75 years,
      therefore further screening is not necessary due to a lack of a therapeutic
      consequence. Curative treatment options enclose as the gold standard surgical
      removal, i.e. open radical prostatectomy with pelvic lymph node dissection, and
      radio-oncologic treatments, be it percutaneous radiation therapy, brachytherapies
      or a combination thereof. Palliative treatment options are mainly hormonal
      treatment (medical or surgical androgen deprivation), local radiation, treatment
      with bisphosphonates, chemotherapy and surgical desobstruction of the prostate.
      Regular follow up allows for early detection of recurrences and an active
      treatment concept.

PMID- 18622956
TI  - [Tumor surveillance after resection of colorectal cancer].
AB  - Because recurrent adenocarcinoma of the colon and rectum (CRC) can still be
      treated with acceptable 5-year survival rates, tumor surveillance plays an
      important role. Early detection of recurrent disease from CRC allows for
      effective treatment with intention for cure. This is why, in 2007, an
      interdisciplinary group modified the popular "FAGAS" criteria, a proposition for
      surveillance after curative resection of colorectal cancer. Proposed are the 3
      monthly follow-up of the tumor marker CEA (carcino embryonic antigen), which, in
      case of lower sigmoid or rectal cancer, would be completed by rectosigmoidoscopy
      and endosonography every 6 months. As a major change liver sonography is now
      proposed to be replaced by annual thoraco-abdominal CT scan. Colonoscopy within
      the first year after resection has its place in the surveillance due to a high
      rate of metachronous secondary tumors missed in the initial endoscopy. Once
      completed it needs not to be repeated for at least 3 years. Only in cases where
      early stage CRC was been completely resected no schematic surveillance must take
      place.

PMID- 18622957
TI  - [Follow-up for cutaneous melanoma].
AB  - Surgical treatment of primary cutaneous melanoma has significantly changed in the
      last decades. Tumors are excised with lateral margins of 1-2 cm depending on the
      depth of tumor infiltration, and reconstructive procedures for defect closure are
      rarely necessary. Elective lymph node dissection has been replaced by the
      sentinel lymph node procedure and radical lymph node dissection is restricted to
      patients with positive lymph nodes. Follow-up of melanoma has been adapted to the
      individual risk profile of the patient. In early stage melanoma only clinical
      follow-up examinations are warranted. Ultrasound investigations of the regional
      lymph nodes is recommended for patients with locally advanced melanoma and with
      lymph nodes metastases. CT-scans, MRI and PET/CT are recommended only for stage
      III patients and it has to be taken into account that these evaluations may have
      only limited value regarding the prognosis of the patients. In stage IV melanoma,
      the follow-up scheme should be adapted to the individual needs of the patient.

PMID- 18622958
TI  - [Follow-up after malignant tumours of the uterus (cancer of the uterine corpus /
      cervical cancer)].
AB  - Malignant uterine tumours can affect the corpus or the cervix. The endometrial
      carcinoma with its different histological subtypes counts for most of the
      malignomas of the uterine body. But the rare category of uterine sarcomas
      (carcinosarcomas, leiomyosarcomas as well as endometrial stromal sarcomas) also
      belongs to this group. Cervical cancer presents an own entitity, regarding both
      histology and therapeutic options. Endometrial cancer is the most common genital
      malignoma in Northern Europe and North America. Histologically, the endometrial
      cancer can be subdivided in two groups: type I is hormonal sensitive and well
      differentiated, type II represents an undifferenciated aggressive tumour with
      poor prognosis. In general, the patient is elderly. Due to the main symptom -
      abnormal vaginal bleeding - endometrial cancer is detected in an early stage in
      about 75% of all patients. First choice in therapy is stage related surgery.
      Follow-up schemes have not proved yet to improve survival, therefore clear
      guidelines are missing. National and international groups recommend regular
      follow-up visits to detect the early vaginal vault relapse which is curable.
      Cervical cancer is mainly a squamous cell carcinoma and oncogenic Human Papilloma
      Virus (HPV) associated. Surgery is only indicated up to stage IIA, advanced
      stages should be treated by radio-chemotherapy. Several studies have shown that
      follow-up visits can improve survival rates. Intention is the detection of the
      curable local relapse.

PMID- 18622959
TI  - [Surveillance after primary resection of esophageal, gastric, pancreatic,
      hepatobiliary cancer and gastrointestinal stroma tumor (GIST)].
AB  - A high rate of recurrence after primary resection is common to all tumor entities
      discussed here. However, there is no scientific evidence that regular
      surveillance after primary surgery changes the natural course of disease.
      Nevertheless, patients with hepatocellular carcinoma and a subgroup of patients
      suffering from other non-colorectal gastrointestinal tumors may benefit from
      selected follow-up examinations. This manuscript gives some practical guidance on
      how to individually follow these patients after primary tumor resection.

PMID- 18622960
TI  - [Assessment of generic and disease-specific health-related quality of life
      instruments in peripheral arterial disease].
AB  - As chronic diseases are continuously increasing in our aging society, the
      description and improvement of quality of medical care needs critical examination
      of the multidimensional subject of "quality of life". Health-related quality of
      life is currently used as an outcome-criterion in modern medicine. As there is no
      generally accepted definition of quality of life, various components of the state
      of health and the patient's behaviour are recorded by questionnaires. The level
      of subjective well- being is determined by several dimensions such as physical
      constitution of the patient, state of mind, functional competency in everyday
      life and the form of interpersonal relationships. Based on these principles
      various instruments for measuring quality of life are developed. The assessment
      of the subjective quality of life reflects the increased acceptance of the
      patient's view. In addition to the common generic instruments such as SF-36,
      FLZ(M), MLDL, EQ-5D, WHOQOL-100, NHP, SIP, also disease-specific instruments e.g.
      for peripheral arterial disease are currently used (PAVK-86, CLAU-S, VASCUQOL,
      SIP(IC), and WIQ). At the moment SF-36 is the best established questionnaire as
      generic QOL instrument. FLZ(M) takes the individual weighting of items into
      account, by correlating the importance and the contentment for life. For
      evaluating the effectivity of medical outcome and the success of therapeutic
      treatment for patients with vascular disease, the VASCUQOL instrument seems to be
      the best choice. Simultaneous application of a generic instrument and disease
      specific questionnaires displays as well the subjective quality of health as the
      individual impairment of the patient in a good way. As a consequence using both
      instruments is superior to the exclusive use of a generic questionnaire.

PMID- 18622961
TI  - Rational diagnostic and treatment of diseases of the cerebrocervical circulation.
AB  - This is an update of current diagnostic and therapeutic strategies for treatment
      of cerebrovascular, predominantly atherosclerotic diseases.

PMID- 18622962
TI  - Morphological features of vasa vasorum in pathologically changed human great
      saphenous vein and its tributaries.
AB  - BACKGROUND: The question whether the primary increase of vasa vasorum (VV) of
      venous wall (i) plays an initial role in varicogenesis or (ii) is an expression
      of impairment of the nutritional conditions in superficial veins of lower
      extremities is not unambiguously solved yet. The aim of the study was to describe
      the arrangement of the VV within the wall of the human great saphenous vein (GSV)
      qualitatively, and of its tributaries at different stages of varicosis and in
      other pathological states like thrombophlebitis or phlebosclerosis. MATERIAL AND
      METHODS: 22 patients deserving an aorto-coronary bypass surgery or GSV surgery
      were subdivided into three groups according to the staging of their varices and
      other pathology. The harvested GSV were prepared for light and scanning electron
      microscopy. One cadaverous specimen of GSV was injected with India ink. RESULTS:
      In specimens from reticular and primary large varices local intimal hyperplasia
      was regularly found, partially accompanied with a mild increase of VV.
      Tortuosities and irregular dilations of adventitial veins were also found. In
      patients with recurrent primary varices or thrombophlebitis severe intimal and
      medial hyperplasia, thrombosis and a striking increase of VV were found. The
      intima remained avascular in all cases. CONCLUSIONS: Remarkable increase of VV
      accompanies the most severe forms of varices as well as all cases of the extreme
      grades of phlebosclerosis, medial hyperplasia and thrombosis. We hypothesize that
      this increase in VV is rather a secondary vascular reaction to the impaired
      metabolic conditions within the venous wall than a primary varicogenic factor.

PMID- 18622963
TI  - Non-invasive assessment of endothelial activity in patients with coronary heart
      disease and cardiovascular risk factors.
AB  - BACKGROUND: The aim of this study was first to compare the widely used flow
      mediated dilation ( FMD ) method with the iontophoretically induced acetylcholine
      vasodilation (IAV ) procedure. The ultimate goal was to examine the endothelial
      activity ( EA ) in patients with various cardiovascular risk factors compared
      with control subjects. PATIENTS AND METHODS: In the upper extremities of 27
      subjects, comparisons of EA by FMD and IAV measured with laser Doppler flux
      method (LDF) were conducted. IAV-EA was then measured using LDF in an additional
      93 subjects with various cardiovascular ( CVD ) risk factors and/or a diagnosis
      of coronary heart disease (CHD). RESULTS: The mean age of the subjects was 56.2
      years and 54% were male. There was a robust and significant correlation between
      FMD vs IAV endothelial activity (r = 0.87, p = 0.025). After adjustment for age,
      there were significant differences in LDF-measured, acetylcholine-induced EA by
      diagnosis of CHD (p = 0.02), hyperlipidemia (p = 0.03) and diabetes (p < 0.01),
      as well as by sex (p < 0.01). The difference by hypertension status was of
      borderline significance (p = 0.07). LDF EA was higher in non-smokers compared to
      smokers but this difference was not statistically significant (p = 0.3). After
      adjustment for age and gender, a 10-unit increase in LDF-measured EA was
      associated with a 12% lower odds for a diagnosis of CHD (p = 0.07). CONCLUSIONS:
      Measurement of IAV-EA by LDF is a simple, noninvasive methodology which is highly
      correlated with post-occlusive FMD EA and is also significantly associated with a
      diagnosis of CHD.

PMID- 18622964
TI  - Immune-response against Streptococcus pyogenes in the development of abdominal
      aortic aneurysm--a population-based case-control study.
AB  - BACKGROUND: In a population-based case-control study the association between
      antibodies to Streptococcus pyogenes antigens and the development of abdominal
      aortic aneurysm (AAA) was analysed. PATIENTS AND METHODS: Forty-two patients with
      screening-detected AAA were compared to 100 age- and sex matched controls with
      normal aortas. Antibodies against three recently characterized cell wall-attached
      proteins of S. pyogenes (SclA, SclB and GRAB) were analysed in plasma samples
      obtained at screening (current), and in samples obtained from a study conducted
      12 years previously on the same population (historical). RESULTS: Historical
      antibody levels against the S. pyogenes antigen GRAB were significantly higher in
      AAA patients compared with controls (0.25 vs 0.17, p = 0.021). A similar trend
      was observed in current GRAB antibody levels (0.23 vs 0.17, p = 0.072). GRAB
      antibody levels at age 60 years retained the association with AAA in a logistic
      regression model after adjustment for a history of atherosclerosis (OR 20.2, p =
      0.022), current smoking (OR 21.4, p = 0.025) and family history of AAA (OR 12.9,
      p = 0.053). Current and historical antibody levels against SclA and SclB in AAA
      patients were similar to those in controls. CONCLUSIONS: The results indicate
      that the immune response against S. pyogenes protein GRAB may be involved in the
      pathogenesis of AAA.

PMID- 18622965
TI  - Intraoperative duplex ultrasonography in carotid endarterectomy: the impact on
      indication for immediate revision and intermediate-term outcome.
AB  - BACKGROUND: Thromboembolic complications in relation to carotid endarterectomies
      (CEA) are frequently associated with technical errors. We analyzed prospectively
      the impact of intraoperative duplex ultrasonography (IODS) in CEA on immediate
      revision and postoperative results. PATIENTS AND METHODS: We have observed 70
      patients with 74 CEA. Indications for surgery were asymptomatic high grade
      stenosis (70-99%) or symptomatic stenosis of > 50%. IODS findings were rated as
      "relevant", "minor" or "normal". Relevant findings were immediately repaired.
      Peri- and postoperative neurological events were analyzed in Duplex Scans
      controls in a median length of follow-up of 17.3 months. Outcome of patients with
      "minor" findings (group A) were compared with patients having "normal" or
      corrected "relevant" findings (group B). RESULTS: In 8/74 cases (11%) we found
      relevant findings leading to immediate revision. In 25/74 (34%) cases minor
      findings were detected which were not revised. In group A (n = 25, 34%) two
      asymptomatic occlusions and one recurrent high grade stenosis were found during
      follow-up. In group B (n = 49, 66%) we detected two high and two low grade
      stenosis. The 30 day death and stroke rate was 1.4% (n = 1). CONCLUSIONS: IODS is
      a sensitive method to detect immediately pathological findings. Its correction
      seems to reduce the incidence of early occlusions and therefore early
      neurological events.

PMID- 18622966
TI  - Generalized dilating diathesis in patients with popliteal arterial aneurysm.
AB  - BACKGROUND: Aim of this study was to analyse the relationship between popliteal
      artery aneurysm (PAA) and generalized arteriomegaly. PATIENTS AND METHODS: In
      this consecutive serie, thirty-three patients (1 woman, mean age 69.7 +/- 9.6
      years) undergoing PAA repair between 1996 and 2000 agreed to participate in a
      duplex screening program to assess the diameters of the infrarenal abdominal
      aorta, common and external iliac, common and superficial femoral and
      contralateral popliteal arteries as well as common carotid and brachial arteries.
      RESULTS: The prevalence of arteriomegaly and aneurysmal disease, respectively,
      was as follows: abdominal aorta 15/33 (45.5%) and 8/33 (24.2%), common iliac
      artery 34/66 (51.5%) and 23/66 (34.8%), common femoral artery 55/66 (83.3%) and
      7/66 (10.6%) as well as contralateral popliteal artery 7/33 (21.2%) 15/33
      (45.5%). Significantly larger carotid artery diameters were found comparing PAA
      patients with age- and body surface adjusted healthy controls (p < 0.001).
      Furthermore, patients with multiple peripheral arterial aneurysms had
      significantly larger diameters of the brachial (p < 0.02) and external iliac (p <
      0.005). CONCLUSIONS: Our findings support the hypothesis of a diathesis for a
      generalized arteriomegaly with a predilection for further aneurysms of the
      abdominal aorta, iliac arteries, femoral and contralateral popliteal arteries in
      patients with PAA.

PMID- 18622967
TI  - Balloon sclerotherapy: a new method for the treatment of truncal varicose veins.
AB  - BACKGROUND: Truncal varicose veins may be treated by conventional surgery or
      endovenous therapy. Endovenous ablation, such as laser or radiofrequency
      treatment, is less invasive but technically demanding, not cheap and has still
      the possibility of important side-effects. Moreover the treatment requires in the
      best case tumescent anesthesia. Catheter based endovenous sclerotherapy has the
      potential of systemic effects of sclerosing agent and air. We therefore aimed to
      develop a simple, minimal-invasive and cheap method for the treatment of truncal
      varicose veins reducing the potential risk of systemic effects of the sclerosing
      agent to a minimum. METHODS: A double lumen double balloon catheter was
      developed. Thereby a treatment site within a vein can be isolated from blood for
      localized administration of a sclerotherapeutic agent. Later, a substantial
      portion of the therapeutic agent can be removed from the isolated segment thus
      minimizing the amount necessary. Occlusion of longer varicose segments is
      achieved by pointwise repetition of the manoeuvre or careful retraction of the
      expanded balloons with the "catched" sclerotherapeutic agent in between. RESULTS:
      The application was filed as United States Patent No. 6,726,67 B2. 18 balloon
      prototypes successfully passed an extensive test series (leak tests, dimension
      tests, mandrel--, guide wire--and introducer compatibility tests, destructive
      tests). Three patients with varicosity of the greater saphenous vein and the vena
      saphena accessoria lateralis, respectively, were successfully treated with
      complete occlusion of the vessels 10, 6 and 2 months after the intervention.
      CONCLUSIONS: Balloonsclerotherapy combines two well-established procedures
      (balloon catheter therapy and sclerotherapy, namely) and promises to be a minimal
      invasive and cheap endovenous therapy of truncal varicose veins, requiring local
      anesthesia at the puncture site only and reducing possible systemic side effects
      of the sclerosing agent.

PMID- 18622968
TI  - Long term outcome after balloon angioplasty and stenting of subclavian artery
      obstruction: a single centre experience.
AB  - INTRODUCTION: Percutaneous transluminal angioplasty is an accepted and successful
      treatment strategy in obstructive disease of the subclavian artery. The purpose
      of this study was to evaluate the technical and clinical long-term outcome
      following endovascular therapy. PATIENTS AND METHODS: We retrospectively analyzed
      99 patients (mean age of 65 +/- 10 years) with 100 interventions of the
      subclavian arteries and the brachiocephalic trunk with different aetiologies
      [atherosclerosis (90%); Takayasu's arteritis (5%); thromboembolism (2%); external
      compression (1%); iatrogenic dissection (1%) and occlusion after graft
      implantation in type B dissection (1%)]. RESULTS: Primary success rate was 97%
      (100% for stenoses and 90% for total occlusions). Treatment modalities included
      balloon angioplasty (PTA) alone (16%), stent implantation (78%), rotational
      thrombectomy (2%) and atherectomy (1%). The primary 1-year patency rate of the
      whole study cohort was 87% being not significantly lower after PTA (75%) compared
      to stent assisted angioplasty (89%). After thrombectomy and atherectomy no
      relevant restenosis were found. Multivariable analysis of 1-year restenosis-free
      survival revealed younger age (p = 0.03) and stenting (p = 0.04) as independent
      predictor. The blood pressure difference between both limbs at baseline was 42 +/
      24 mmHg and dropped to 10 +/- 14 mmHg after the intervention and 15 +/- 20 mmHg
      after 12 months, respectively (p = 0.01). CONCLUSIONS: Endovascular therapy of
      subclavian artery obstructions of various aetiologies offers good acute success
      rates even in total occlusions. Long-term patency rate is in favour of stent
      placement.

PMID- 18622969
TI  - [Ascending aortic and pulmonary trunk aneurysms].
AB  - A case of two non-atherosclerotic aneurysms localised in the ascending aorta and
      in the pulmonary trunk is presented. Histopathologically, a severe granulomatous
      inflammation affecting the whole aneurysms wall was documented. To the best of
      our knowledge it is the second ever documented case of simultaneous occurrence of
      aneurysms in the aorta and the pulmonary artery.

PMID- 18622970
TI  - Proteus' syndrome as a differential diagnosis of vascular malformations.

PMID- 18622974
TI  - [Plea for retaining section 105--knowledge of brain development].

PMID- 18622971
TI  - Peripheral arterial disease and thrombophilia.

PMID- 18622975
TI  - [Trauma and traumatic disorders in children and adolescents].
AB  - In recent years, the definitions of trauma and individual criteria of
      posttraumatic disorders as defined in ICD-10 and DSM-IV have been critically
      discussed. The category of acute stress disorder is questioned due to an over
      emphasis on dissociative symptoms and a pathologizing of normal reactions after
      trauma. The criteria for posttraumatic stress disorder, especially those with
      regard to childhood and adolescence, need revision. Scheeringa and co-workers
      have since defined PTSD-criteria that are more suitable and specific for
      posttraumatic reactions and disorders in toddlers and children. Moreover, the
      "Complex Trauma Taskforce" of the National Child Traumatic Stress Network
      proposes a diagnosis called Developmental Trauma Disorder to better capture the
      problems of children suffering from early and complex traumata.

PMID- 18622976
TI  - [The mental status of overweight children].
AB  - OBJECTIVE: Numerous studies based on parent questionnaires reveal that obese
      children are subject to both physical and psychosocial strains. Children are not
      included as informants in the assessment procedure, and there is a lack of
      clinical interview studies assessing DSM-IV-based diagnoses in overweight
      children. METHODS: Emotional and behavioural problems of treatment seeking obese
      children (N = 59; aged 8-12-years) attending a mental health service were
      assessed by means of clinical interviews (Kinder-DIPS) that included child and
      parent reports. In addition, Child Behavior Checklist (CBCL) data (N = 55)
      available for this clinical sample were compared with data of a representative
      sample of normal-weight children (N = 1,080). Furthermore, CBCL data of the
      clinical subsample of 10-12 year-old overweight children (N = 34) were compared
      with data of a subsample of 10-12 year-old overweight children (N = 33) and of
      the subsample of normal-weight (N = 386) children from a representative
      population, both matched by sex. RESULTS: 23 children (39%) met full criteria for
      a psychiatric disorder according to DSM-IV, and 19 (34.5%), nearly one third,
      suffered from Binge Eating Disorder (BED). The overweight clinical sample and
      their normal weight peers differed significantly on 6 of the 8 primary syndrome
      scales, on the internalizing and the externalizing scores, and on the total
      problem score of the CBCL. The overweight children in the clinical sample scored
      significantly higher than the overweight children in the representative sample on
      the subscale measuring social problems and the total score, with BMI accounting
      for the difference in total score. Within the representative sample, overweight
      10-12 year-old children scored significantly higher than their normal weight
      peers on two scales measuring delinquency and social problems. CONCLUSION: A
      third of the obese children had mental disorders and behaviour problems. This
      finding applies to clinically referred obese children and, to a much lesser
      degree, to nonclinical obese subgroups in the normal population. Clinically obese
      children constitute a patient group that is in urgent need of multimodal
      treatment. As a consequence, a major change in treatment and prevention of
      childhood obesity is warranted, i.e., from the mere treatment of eating and
      activity behaviours to the inclusion of treatment of co-morbid mental disorder
      and prevention of chronification.

PMID- 18622977
TI  - [Mental disorders among relatives of patients with anorexia nervosa and bulimia
      nervosa].
AB  - BACKGROUND: Family studies of anorexia (AN) and bulimia (BN) nervosa in relatives
      of patients with eating disorders compared to control subjects are rare in German
      speaking countries. METHODS: A German multicenter study compared first-, second-
      and third-degree relatives of 65 adolescent AN subjects (n = 746), 21 adolescent
      BN subjects (n = 265) and relatives of 11 adolescent depressive control subjects
      (n = 157), as well as those of 37 adolescent healthy control subjects (n = 480).
      Assessments included the Diagnostic Interview for Genetic Studies (DIGS), the
      short form of the Family Interview of Genetic Studies (FIGS), and the Eating
      Disorder Family History Interview. RESULTS: Rates of anorexia nervosa and major
      depressive disorder (trend) were significantly (p < .01) higher among the first-
      and second-degree relatives of anorexic and bulimic subjects than among the
      relatives of healthy controls. Most results were more prominent among relatives
      of bulimic index patients. Nevertheless, the frequencies were lower in this
      sample than in comparable US-American samples. CONCLUSIONS: The data confirm the
      hypothesis of familial vulnerability to anorexia and bulimia nervosa. The
      observed differences in comorbidity patterns among eating-disordered relatives
      may be due to an age effect of the index patients.

PMID- 18622978
TI  - Personality correlates of physiological response to stress among incarcerated
      juveniles.
AB  - BACKGROUND: To examine the relationship between personality type and
      physiological response to stress among juvenile delinquents. METHODS: Delinquent
      males (N = 42, mean age 16.5, SD = 1) recruited from a convenience sample at
      local juvenile detention facility were compared to a male control sample from a
      local high school (N = 79; mean age 16.1, SD = 0.8). All participants completed
      the Weinberger Adjustment Inventory and a Stress-Inducing Speech Task during both
      of which heart rate was measured. RESULTS: Compared to controls, delinquent
      youths showed significantly lower heart rates under both free association and
      stress conditions (p < 0.05) and a lower rate of increase during stressful
      stimuli (p < 0.05). Among delinquents, those with a non-reactive personality type
      appeared to show consistently lower levels of physiological arousal as measured
      by heart rate. CONCLUSIONS: Delinquents consistently had lower overall levels of
      arousal as measured by heart rate. In delinquent boys, we also found a
      persistently low arousal group with a non-reactive psychological pattern. This
      combination may be a forerunner of future psychopathy or a product of the
      developmental trajectory that leads to and results from psychopathic behavior.

PMID- 18622979
TI  - [Twenty-year follow-up investigation of the Clinic for Child and Adolescent
      Psychiatry "Haus Vogt"].
AB  - OBJECTIVES: The present study analyses the long-term course of disease among
      patients who underwent inpatient psychotherapeutic treatment in a psychiatric
      hospital for children and adolescents. METHODS: Assessed within the study was a
      sample of former patients (N = 104) hospitalised in "Haus Vogt" for at least six
      months from 1983 to 1988. The following instruments were used: Freiburger
      Strukturiertes Interview (FrStI), World Health Organisation Quality of Life
      Interview - short version (WHOQOL-BREF), Symptom Checklist of Derogatis - German
      version (SCL-90-R) and questionnaires for the assessment of the treatment (FBB).
      RESULTS: The quality of life (according to WHOQOL-BREF) of former patients is
      significantly worse on all relevant scales than that among the general
      population. The mental health (according to SCL-90-R) of the assessed sample is
      under average compared to that of the general population. In retrospect,
      satisfaction with treatment, as investigated by means of the FBB, differed
      considerably between the former "Haus Vogt" patient sample and a comparative
      sample from a psychiatric university hospital for children and adolescents. The
      biggest differences in satisfaction with treatment were found on the scale
      relationship with the therapist, which was much worse among the sample of former
      "Haus Vogt" patients than in the control group. CONCLUSIONS: The study shows
      positive long-term results in terms of the school and professional education
      attained later on. At the same time, the former patients showed persisting
      psychiatric symptoms and a considerably restricted quality of life.

PMID- 18622980
TI  - [The relationship between the experience and success of inpatient psychotherapy
      treatment among children and adolescents].
AB  - OBJECTIVE: Examined here is the degree to which particular aspects of treatment
      experience in the inpatient psychotherapy of children and adolescents correlate
      significantly with the actual success of treatment. METHODOLOGY: Data of 95
      patients hospitalised between 2002 and 2006 in the Department of Child and
      Adolescent Clinical Psychotherapy at the NLKH Tiefenbrunn were analysed. To
      assess the relationships multiple regression analyses were carried out, whereby
      the dependent variable was on the one hand, the retrospective estimate of
      treatment success by the patients by means of the Questionnaire to Assess
      Treatment (Fragebogen zur Beurteilung der Behandlung/FBB), and on the other, the
      difference on the General-Severity-Index (GSI) of the Symptom Checklist 90-R (SCL
      90-R) between the time of admission and release from hospital. Patients'
      experience of treatment was assessed by MEANS OF THE WARD EXPERIENCE
      QUESTIONNAIRE (STATIONSERFAHRUNGSBOGEN/SEB) BY SAMMET AND SCHAUENBURG (1999).
      RESULTS: The direct measurement of success (FBB-P-Scale Success of Treatment)
      correlated highly significantly with the SEB scales Expectation of Self-Efficacy,
      Individual Therapeutic Relationship, Atmosphere among Co-Patients, Group
      Cohesion, Relationship to Therapy Team, Intensity of Treatment, and with the
      Difference in the Estimate of Individual Therapeutic Relationship between Patient
      and Therapist. The indirect measure of success also correlated highly
      significantly with the Atmosphere among Co-Patients and the perceived Expectation
      of Self-Efficacy. The relationship between the Relationship to Therapy Team was
      also significant at the 5% level. In the subsequent regression analyses the SEB
      scales explained 51% of the variance between the retrospective estimates of
      success (FBB). The subscales Relationship to Therapy Team (beta= 0.47, t(df) =
      4.15(84), p < .01) and Expectation of Self-Efficacy (beta = 0.32, t(df) =
      3.30(84), p < .01) proved to be significant predictors of treatment success.
      Using the difference in the GSI values on the SCL-90-R as the dependent variable,
      the SEB scales explained 23% of the variance in treatment success, whereby
      Atmosphere among Co-Patients was the only significant individual subscale (beta =
      0.35, t(df) = 2.63(84), p < .01). CONCLUSIONS: The success of inpatient
      psychotherapy treatment among children and adolescents in the sample studied
      correlated significantly with particular aspects of treatment experience. In this
      connection, the reduction in symptoms apparent in the comparison of values at
      admission with those at release seems to be primarily related to the Atmosphere
      among Co-Patients, whereas the success of treatment as estimated directly by the
      patients correlates more strongly with Relationship to Therapy Team and
      Expectation of Self-Efficacy. Due to the correlative design of the study, the
      issue of causality could not be completely resolved.

PMID- 18622989
TI  - [Pain management in patients with cognitive impairment: a research implementation
      project].
AB  - People with cognitive impairment and consecutive communication disturbance are,
      due to their illness, a very vulnerable group of patients. They are particularly
      at risk that their pain is not well assessed and therefore often not treated
      adequately. Insufficient pain management however impacts health status and
      decreases cognitive functioning and the patients' quality of life. The aim of the
      evidence-based practice development project was to establish a systematic pain
      management for cognitively impaired patients on a surgical ward of a regional
      hospital. Based on a literature review a quality standard and an algorithm
      including the pain assessment instrument BESD were developed and subsequently
      implemented. The project was evaluated by obtaining data from the patients charts
      and by interviewing the nurses. Ten patients were included in the project. First
      results showed that pain was individually assessed with the patients in each
      shift and that pain was treated both with and without medication. Nurses paid
      more attention to pain assessment and improved their practice of structured
      assessments in patients with severe cognitive impairment. We therefore recommend
      applying both the standard and the pain assessment instrument BESD with
      cognitively impaired patients.

PMID- 18622990
TI  - [Discharge planning of elderly patients in need of care].
AB  - The following article is based on a survey about the perception of elderly
      patients concerning their discharge from hospital. This includes all activities
      carried out at the hospital to prepare the patients for further treatment and
      care after discharge if necessary. 63 elderly patients from the department of
      internal medicine of a general hospital in Lower Saxony were interviewed using a
      standardized questionnaire. The results of this survey show that many patients
      interviewed were neither feeling informed nor did they learn how to cope with the
      situation after discharge from hospital. A quarter of all interviewed patients
      realized neither their involvement nor the involvement of their family in
      planning the essential steps required for the time of discharge from hospital. We
      found out that being involved in discharge planning has a great influence not
      only on the satisfaction with the preparation for discharge from hospital but
      with the entire hospital care.

PMID- 18622991
TI  - [IDAK--inter-professional documentation of lung cancer patients' information
      regarding their status in the hospital].
AB  - The abbreviation IDAK stands for the documentation paper developed and tested
      during the project: Inter-professional Documentation of information (German:
      Aufklarung) in the hospital (German: Krankenhaus). OBJECTIVE: The aim of the IDAK
      project was to evaluate one documentation system for both medical and nursing
      staff about what the patients know regarding their diagnosis and prognosis.
      Accurate documentation of the patients' status of being well-informed should help
      to realize congruent communication by the nurses. METHODS: The case control study
      was undertaken with patients suffering from lung cancer; it aimed to show that
      nurses knowing about what the patients know, will be more confident in talks and
      stay longer at the bedside. After the descriptive examination the data were
      subjected to an explorative analysis. RESULTS: We collected data for 76 daily
      profiles in the intervention group and 69 in the control group (N=145). In the
      intervention group we could detect a significantly higher contact time per
      conversation (intervention group 2:46 min; SD 1:05; SE 0:07, control group 2:19
      min; SD 0:40; SE 0:04; Mann-Whitney: p(0.05)=0.016). The result of this study
      shows how often and for how long it is possible for patients with lung cancer to
      exchange information with nursing staff, but the result is too poor for showing
      an effect of the IDAK documentation.

PMID- 18622992
TI  - [Measuring patient satisfaction in an emergency unit of a Swiss university
      hospital: concept clarification and results (part 1)].
AB  - This article reports parts of a comprehensive study examining ambulatory
      patients' satisfaction with nursing care in a Swiss emergency department. Former
      studies have focused on patients discharged to hospital wards while nursing
      specific patient satisfaction results are missing. Patient satisfaction entails
      the following three dimensions: "Interaction/interpersonal dimension",
      "information/patient participation", and "nurses' knowledge". A descriptive cross
      sectional study examined patient satisfaction using a revised version of the
      questionnaire "Patient satisfaction with nursing care" in a convenience sample of
      114 patients. The instrument measures patient satisfaction by means of 37 items
      on a 5-point Likert-scale. As target values 85% of the maximum scores in each
      dimension were chosen as cut-off scores. Total scores and their means were
      computed for all dimensions of patient satisfaction and criterion validity was
      analyzed. Concurrently, the psychometric characteristics of the measurement
      instrument were tested. No patient achieved the maximum total score and the
      target values for "Interaction/interpersonal dimension", information/patient
      participation, and "nurses' knowledge" were not attained. The items "I had trust
      in the nurses" and "During conversation/while talking with nurses, no disturbing
      others were present" showed the highest scores in the "Interaction/interpersonal"
      dimension. The item "Nurses showed interest about what the illness means for my
      daily life" showed the lowest scores. In the dimensions "information/patient
      participation" and "nurses knowledge", patients missed nurses' caring for their
      psychological/emotional wellbeing, thirst, hunger and self-care deficits in
      bathing/hygiene. The overall results were not generally low, but demonstrate
      potential for quality enhancement. The measurement instrument showed good
      reliability (Cronbachs' alpha .83, .82, .70) and criterion validity was
      supported. Further results will be presented and discussed in part two of the
      study (Muller-Staub, Meer, Briner, Probst & Needham, 2008).

PMID- 18622993
TI  - [Measuring patient satisfaction in an emergency unit of a Swiss university
      hospital: occurrence of anxiety, insecurity, worry, pain, dyspnoea, nausea,
      thirst and hunger, and their correlation with patient satisfaction (part 2)].
AB  - This article reports the second part of a comprehensive study examining patient
      satisfaction with nursing care in ambulatory patients of a Swiss emergency
      department. A descriptive cross-sectional study examined patient satisfaction,
      using a revised version of the questionnaire <<Patient satisfaction with nursing
      care>> in a convenience sample of 114 patients. The occurrence and intensity of
      anxiety, insecurity, worry, pain, dyspnoea, nausea, thirst and hunger, and their
      correlation with patient satisfaction were analyzed. The patients also reported
      if effective nursing interventions were carried out. Patients suffered from the
      following states or symptoms: Pain (70%), thirst (45%), insecurity (44%), anxiety
      (38%), hunger (25%), and nausea (12%). Despite the occurrence of these states or
      symptoms, not all patients reported receiving effective nursing interventions.
      Dyspnoea and pain were detected well by nurses and patients received effective
      nursing interventions. Anxiety, insecurity, nausea, thirst and hunger were not
      detected well by nurses; and patients often evaluated the nursing interventions
      they received as ineffective. These results were analyzed and compared with the
      findings measured by the instrument "Patient satisfaction with nursing care"
      applying correlations and ANOVA. Patients who suffered from the states or
      symptoms described above and reported receiving ineffective nursing interventions
      showed significantly lower patient satisfaction scores than patients not
      suffering from these states or symptoms. Statistically significant correlations
      were found between worry, pain, anxiety and patient satisfaction. The results of
      both studies (part 1+2) (Muller-Staub, Meer, Briner, Probst & Needham, 2008) are
      discussed, conclusions drawn and implications for practice and research
      presented.

PMID- 18622994
TI  - [Karen Kersting: "Smart concepts" for improving the status of nursing or on the
      perspectives of critical nursing science].

PMID- 18622995
TI  - [Karen Kersting: "Smart concepts" for improving the status of nursing or on the
      perspectives of critical nursing science].

PMID- 18622996
TI  - [Incidence and risk recording of pressure ulcers: results of quality measurement
      of the Verein Outcome in Swiss hospitals].
AB  - Avoidance of ulcers is one of the key duties of nursing professionals. A low rate
      of decubitus ulcer is an indicator for the quality of nursing. The Verein Outcome
      (Switzerland) collected data on the incidence of ulcers in 51 hospitals with a
      total of 88 636 patients. Additionally, the data included an analysis of the
      severity of the impairment, a risk assessment, and an inquiry of the predictive
      validity of the Norton scale. The incidence turned out to be rather low at 3.1%.
      2.6% of all patients came into treatment with an ulcer already in existence while
      3.8% were still suffering from an ulcer at the time of their discharge. Although
      these rates can be considered low compared to rates cited in international
      studies, changes in routine care should be implemented for the subsequent benefit
      of future patients. Using the Norton scale, 9.5% of all patients were at risk for
      developing an ulcer, and 14% of this group actually formed one. The use of the
      Norton scale has a tendency to overestimate the risk of ulcer development. The
      sensitivity of the Norton scale was computed to be at 42.4%, whereas the
      specificity scored 91.5%. Enhancements of the Norton scale, therefore, are
      essential as a comprehensive, reproducible, and transparent risk assessment is an
      efficient prophylactic method for the avoidance of ulcers.

PMID- 18622997
TI  - [Interrater reliability of the Braden scale].
AB  - Pressure ulcer risk assessment scales can assist nurses in determining the
      individual pressure ulcer risk. Although the Braden scale is widely used
      throughout Germany, its psychometric properties are yet unknown. The aim of the
      study was to determine the interrater reliability of the Braden scale and to
      compare the results with those of published data. A literature review was
      conducted. 20 studies measuring the interrater reliability of the Braden scale
      were evaluated. Only three of those studies investigated the interrater
      reliability of single items. The Pearson product-moment correlation coefficient
      (0.80 to 1.00) was calculated in most studies for an evaluation of the Braden
      scale as a whole. However, the use of correlation coefficients is inappropriate
      for measuring the interrater reliability of the Braden scale. Measures of the
      intraclass correlation coefficient varied from 0.83 to 0.99. The investigation of
      the interrater reliability of the Braden scale's German version was conducted in
      a German nursing home in 2006. Nurses independently rated 18 and 32 residents
      twice. Nurses achieved the highest agreement when rating the items "friction and
      shear" and "activity" (overall proportion of agreement = 0.67 to 0.84, Cohen's
      Kappa = 0.57 to 0.73). The lowest agreement was achieved when the item
      "nutrition" (overall proportion of agreement = 0.47 to 0.51, Cohen's Kappa = 0.28
      to 0.30) was rated. For 66% of the rated residents the difference in the obtained
      Braden scores was equal or less than one point. Intraclass correlation
      coefficients were 0.91 (95% confidence interval 0.82 to 0.96) and 0.88 (95%
      confidence interval 0.61 to 0.96). This indicates that the interrater reliability
      of the Braden scale was high in the examined setting.

PMID- 18622998
TI  - [Self-rating and external rating of how women cope with breast cancer in the
      perioperative phase].
AB  - Little is known both about how women suffering from breast cancer cope with their
      illness in the perioperative phase and about the ability of nurses to assess
      this. By means of the self-rating and external rating versions respectively of
      the Bernese Coping Modes (BEFO), it was determined how breast cancer patients
      cope with their illness during primary surgical therapy. External rating was
      carried out by the nurses and two researchers. The nurses' rating based on their
      daily care experiences, and the researcher's rating based on a half-standardized
      interview. Participants were given the BEFO self-rating questionnaire. As with
      the patients themselves, the nurses and team members rated attention and care
      (H(A) 90,5-100%), tackling (H(A) 66,7-100%), passive co-operation (H(A) 59,5
      100%) and acceptance/stoicism (H(A) 64,3-97,6%) as the strongest forms of coping.
      In ranking order of coping modes the researchers rated dissimulation and
      isolation/suppression and the nurses rated altruism much higher than the patients
      themselves. Several forms of coping revealed a clear dependence on age. The
      discrepancy between the ranking order of the nurses' rating versions and the
      patients' self-ratings were discussed on the basis of empirical findings on
      communication events between nurses and patients.

PMID- 18622999
TI  - [Impact of patient education on self-care behaviour in patients with heart
      failure: a review of the literature].
AB  - Heart failure is a highly prevalent chronic condition. Nurse-led patient
      education has been described in the literature as a key component of disease
      management programs. This literature review investigates the impact of patient
      education on self-care behaviour in patients with heart failure. Seven randomised
      controlled trials could be included in the review. Medication taking, daily
      weighing, salt and fluid restriction and taking action in case of worsening
      symptoms are cornerstones in patient education programs. All seven studies
      revealed that interventions comprising patient education were associated with
      improved self-care behaviour in patients with heart failure. The education has to
      be individualized and family members should be included. Nurses play an important
      role in patient education interventions and must be well trained and skilled for
      example in clinical assessment. To date, the dose and the length of the patient
      education interventions necessary to improve self-care behaviour and sustain
      these behaviours remain unclear and need more research.

PMID- 18623000
TI  - [Job rotation in anaesthesiological care: impacts on knowledge and learning].
AB  - Job rotation in anaesthesiological care is explored in this article. Based on
      discussions of 'high reliability organizations', and based on current theory in
      social and organizational psychology, we empirically investigated the impact of
      job rotation on knowledge management and learning. The study was conducted at the
      University Hospital of Innsbruck during the job training period of novice nurse
      anaesthetists. Qualitative interviews were conducted as well as a questionnaire
      administered. Data were collected between September 2003 and June 2005.
      Observational and interview data were combined with a questionnaire study to
      assess transactive memory and cooperation using a mixed-method design.
      Qualitative data were analyzed using GABEK, a computer-supported content analysis
      system; quantitative data were analyzed statistically with SPSS. Results indicate
      that job rotation had both positive and negative effects on knowledge and
      learning. On the one hand, job rotation can foster flexibility and awareness of a
      person's own fallibility and lack of knowledge. On the other hand, trust, group
      cohesion, and social meta-knowledge can be hampered by constant rotation.
      Consequently, stabilization and change need equal consideration when designing
      work in high reliability organizations.

PMID- 18623002
TI  - [Long-term cognitive dysfunctions in preterm subjects with intraventricular
      haemorrhage].
AB  - INTRODUCTION: Intraventricular hemorrhage (IVH) in the neonatal period has been
      associated to developmental impairment or delay in preterm born children and
      adolescents. To our knowledge there is no study in literature which describes the
      effects of neonatal IVH in preterm subjects on different specific cognitive
      functions in adolescent samples. AIM. To explore general as well as specific
      cognitive performance in preterm adolescents with neonatal IVH, through a
      comprehensive neuropsychological assessment. SUBJECTS AND METHODS: Sixteen
      preterm born adolescents with IVH in the newborn period and thirty matched
      controls were recruited for neuropsychological testing. The intelligence
      quotient, learning, memory, visuospatial and visuoperceptive abilities, and
      frontal functions were evaluated. RESULTS: Significant differences were observed
      for full and performance intelligence quotient, as well as for several specific
      cognitive functions. After controlling for full intelligence quotient, and
      compared with preterm adolescents without IVH, differences remained significant
      for verbal learning and verbal memory. Subjects with IVH grades III-IV scored
      significantly lower than those with IVH grades I-II in verbal learning, everyday
      memory and visuoconstructive and visuospatial abilities. CONCLUSIONS: The present
      study suggests that long-term difficulties are evident for general cognitive
      performance as well as for specific cognitive abilities in preterm subjects with
      IVH in the newborn period. These data could explain the academic problems shown
      by these individuals and may suggest concrete intervention programs to minimize
      the effects of such deficits.

PMID- 18623003
TI  - [The effect of age in a planning and arranging task ('Mexican pyramid') among
      schoolchildren].
AB  - AIM: To analyze the influence of age on the performance of a planning and
      organization task, two skills included in the executive functions. SUBJECTS AND
      METHODS: Performance of the task 'Mexican pyramid' from the Evaluacion
      Neuropsicologica Infantil (ENI) were analyzed on 239 school age children from
      Mexico and Colombia, distributed in six age groups. Five measures were analyzed:
      number of correct designs, number of movements per design and execution time in
      the correct designs, number of correct designs built with the minimum of
      movements and its execution time. RESULTS: There was a significant effect of age
      on the five measures. Comparison between groups showed that younger children (5
      to 6 years old) had a smaller number of correct designs, while children from 5 to
      8 years old need more movements. Execution time showed a greater number of
      differences between groups. Analyzing the 11 items of the task, it was evident
      that difficulty level is related with the number of movements and the novelty of
      rules. CONCLUSIONS: Our results suggest that accuracy of performance, the number
      of moves as well as the speed of performance are useful markers of the
      development of the executive functions. Our results support the notion that the
      development of planning and organization; is fast in the first years of the
      school age, and it slows down on adolescence.

PMID- 18623004
TI  - [Phenotypic characterisation of 35 Colombian children with an imaging diagnosis
      of schizencephaly].
AB  - INTRODUCTION: Schizencephaly is the most frequent neuronal migration disorder. It
      is classified according to the type of lip (closed or open). Clinical features
      vary from the asymptomatic patient to severe neurological compromise. AIM: To
      describe the clinical characteristics of children who have been diagnosed with
      schizencephaly and their correlation with radiological findings. PATIENTS AND
      METHODS: Thirty-five Colombian children (17 males and 18 females) with a
      neuroimaging diagnosis at a mean age of 20.2 months were characterised
      phenotypically. RESULTS: A history of perinatal events such as neonatal asphyxia
      (21.6%) and meconium-stained amniotic fluid (10.8%) were detected, together with
      maternal histories of failure to attend prenatal check-ups (34.3%), risk of
      preterm labour (10.8%) and smoking (10.8%). Familial histories of neurological
      diseases included epilepsy (14.3%) and mental retardation (5.7%). The open-lip
      type was predominant (60%) and was twice a common as the closed-lip type.
      Unilateral cases accounted for 62.9% of the total number, with a distribution
      between the two hemispheres in the same proportion, and 37.1% of cases were
      bilateral. The frontal lobe that was the most commonly involved. The most
      frequent manifestations were delayed psychomotor development (80%) and infantile
      cerebral palsy (80%). Epilepsy was present in 37.1% of cases and the predominant
      type of seizure was complex focal. CONCLUSIONS: Tendencies similar to those
      reported in other series were observed, although with some differences, such as
      the higher mean age at the time of diagnosis and the lower incidence of resistant
      epilepsy. Limited access to prenatal check-ups, open-lip presentation, associated
      malformations and poor response to treatment seem to exacerbate the prognosis.

PMID- 18623005
TI  - [Sinus pericranii. A case report].
AB  - INTRODUCTION: Sinus pericranii is an unusual vascular anomaly characterised by
      communication between diploic and epicranial veins and a dural sinus. It is
      therefore an abnormal communication between the intracranial and extracranial
      circulatory systems. CASE REPORT: We report a case of sinus pericranii in an 8
      month-old boy, with typical clinical and radiological manifestations.
      CONCLUSIONS: Sinus pericranii is a rare condition in paediatric pathology, which
      is generally asymptomatic and is usually found in the area of the anterior
      fontanelle. The fundamental diagnostic method is magnetic resonance imaging of
      the brain with and without contrast; surgery is the preferred treatment, although
      rare cases of spontaneous thrombosis have been reported.

PMID- 18623006
TI  - [Larsen syndrome: two reports of cases with spinal cord compromise].
AB  - INTRODUCTION: Larsen syndrome is characterised by untreatable congenital
      dislocation of multiple body joints, along with marked foot deformities. These
      patients have a flattened face with a short nose, a broad depressed nasal bridge
      and a prominent forehead. In this clinical note our aim is to report two cases
      that coursed with spinal cord compromise. CASE REPORTS: Case 1: an 18-month-old
      female with congenital dislocation of knees and hips. The patient had a flat
      face, sunken root of nose, and carp mouth. Magnetic resonance imaging of the
      spine showed severe cervical kyphosis secondary to malformation and hypoplasia of
      the cervical vertebral bodies and important compression of the spinal cord.
      Clinically, there were also signs of upper motor neuron syndrome, which was
      especially prominent in the lower limbs. Case 2: a 14-year-old male with a
      characteristic face and dislocation of the head of the radius. The patient
      presented amyotrophy of the muscles in the right hand and clinical signs of lower
      motor neuron syndrome due to neuronal damage secondary to spinal malformations.
      CONCLUSIONS: Larsen syndrome is an infrequent osteochondrodysplasia. Alteration
      of the spine is common and may give rise to spinal cord compression with varying
      clinical repercussions which require surgical treatment in the early years of the
      patient's life.

PMID- 18623007
TI  - [Neural bases of contextual modulation in associative learning].
AB  - INTRODUCTION AND DEVELOPMENT: The contextual cues can modulate the conditioned
      response in numerous paradigms of learning. The brain mechanisms necessary for
      this contextual effect on learning are unknown. The objective of this review is
      to show the known aspects of the neurobiology of contextual learning and the
      contextual modulation of learning. CONCLUSIONS: The results indicate that the
      hippocampus and amygdala participate in a different way in the context-learning
      relation, depending on the contextual cues and the behavioural paradigm used.
      Others areas, like nucleus accumbens, striatum, and several cortical areas, also
      could operate in some contextual learning.

PMID- 18623008
TI  - [The clinical use of auto-antibodies in neurology].
AB  - INTRODUCTION: Auto-antibody determinations are very important in current clinical
      practice, not only in immunology or rheumatology but also in the neurosciences.
      These antibodies have both diagnostic and prognostic implications which,
      unfortunately, are often overused or are granted undue importance when it comes
      to interpreting them. On requesting their determination it is therefore necessary
      to know their indications, utility and application. AIM: To present a series of
      auto-antibodies that are relatively commonly used in neurology and which have
      primary and secondary effects on both the central and the peripheral nervous
      system, including the neuromuscular junction and muscle tissue. DEVELOPMENT: In
      this review we cover a series of different conditions, including diseases such as
      vasculitis, cerebrovascular disease, neurological paraneoplastic syndromes,
      dysimmune polyneuropathies and inflammatory myopathies. Special attention is
      given, when relevant, to the indications and, particularly, to the value and
      weight that should be granted to both positive and negative results. CONCLUSIONS:
      Appropriate interpretation and knowledge of the scope and limitations of auto
      antibodies are essential, because otherwise they will lead to mistaken diagnoses
      and, consequently, erroneous treatment.

PMID- 18623009
TI  - [The development of neurotoxic agents as chemical weapons during the National
      Socialist period in Germany].
AB  - INTRODUCTION: The discovery and development of the so-called 'nerve agents'
      (neurotoxic substances to be used as weapons) took place in the Third Reich,
      largely thanks to the vast amount of progress being made in pharmacology in
      Germany at that time, both in academic and industrial terms. Furthermore,
      successive National Socialist governments set up a collaborative network made up
      of the academia, the chemical industry and military chiefs that also favoured
      this line of research. DEVELOPMENT: The first neurotoxic substance to be
      incorporated into the category of 'chemical warfare agent' did so almost wholly
      by chance. As part of the work being carried out on organophosphate-type
      pesticides and insecticides, Gerald Schrader, a chemist at the I.G. Farben
      company, synthesised tabun (ethyl N,N-dimethylphosphoramidocyanidate) and an
      incident involving accidental contamination of laboratory staff with this
      substance highlighted its potential toxicity. The same group of researchers later
      synthesised another substance with the same properties, sarin (isopropyl
      methylphosphonofluoridate). Both agents were studied for use as chemical weapons
      by Wolfgang Wirth. At the same time, a group led by Richard Kuhn, who won the
      Nobel Prize in Chemistry in 1938, synthesised pinacolyl
      methylphosphonofluoridate, otherwise known as soman. CONCLUSIONS: Pharmacological
      studies confirmed that the neurotoxic mechanism of action of these substances was
      the irreversible inhibition of the enzyme acetylcholinesterase, which is
      responsible for metabolising acetylcholine. Results also showed that an excess of
      this neurotransmitter led to a continuous over-stimulation of the cholinergic
      (nicotinic and muscarinic) receptors, which is what triggers the appearance of
      the wide range of symptoms of poisoning and their swift fatal effect.

PMID- 18623010
TI  - [Hyperthyroidism mimicking a motor neuron disease].

PMID- 18623011
TI  - [Ischaemic stroke and sexual headache].

PMID- 18623012
TI  - [Association between meningioma and brain aneurysm in a patient with chronic lead
      poisoning].

PMID- 18623013
TI  - [The effects of treadmill exercise with body weight support on osteoporosis and
      spasticity in spinal cord injuries].

PMID- 18623015
TI  - Micropipette tips--the unsung heroes of mass spectrometry.
AB  - Micropipette tip (tip) pipetting accuracy and precision are functions of tip
      manufacture consistency, morphological variation, and retained inner tip wall
      particulate matter. Irregular tip inner wall surfaces and retained particulate
      matter cause pipetting inaccuracy. Washed and unwashed tips from seven
      manufacturers were compared using weight by difference (six), microscopic Luxol
      Fast Blue staining (seven), and matrix-assisted laser desorption/onization time
      of-flight (MALDI-TOF) mass spectrometry (six). Photomicrographs revealed tip
      irregularity and inner wall retained particulate matter. Computer model analysis
      was used to identify tip irregularity and retained matter. These tests
      established the utility of a pipette solvent wash to increase the performance and
      the accuracy of tips and, thus, improve the MALDI mass spectra obtained.

PMID- 18623016
TI  - Resin comparison and fast automated stepwise conventional synthesis of human SDF
      1alpha.
AB  - Human SDF-1alpha contains 68 amino acids and is a member of the chemokine family
      of peptides. This long peptide was synthesized stepwise using classical
      conditions in 101 h. The reaction times were then reduced to deprotection times
      of 2 x 2 min and coupling times of 2 x 2.5 min, resulting in a total synthesis
      time of 22 h. The effect of different resins, resin substitutions and
      deprotection reagents on the crude peptide purities was compared. A small portion
      of crude peptide was purified using an RP-HPLC column and the mass of the final
      product was confirmed with MALDI-TOF mass spectrometry.

PMID- 18623018
TI  - Removal of cytokines from HAS-containing solutions by adsorption onto silica.
AB  - Septic shock syndrome is a potentially fatal medical condition that is associated
      with elevated blood levels of low molecular weight proteins known as cytokines.
      Adsorption was investigated as a potential method for removing cytokines from
      blood. Saline with 50 mg/mL human serum albumin (HAS) spiked with pathological
      concentrations (ng-pg/mL) of radiolabeled cytokine was used to study cytokine
      adsorption. Adsorption isotherms were linear in the pathological concentration
      range, with adsorption constants ranging from 33.0 mL/g to 173 mL/g for tumor
      necrosis factor (TNF-alpha), interleukin-8 (IL-8),interleukin-6 (IL-6), and C3a.
      Adsorption constants were also determined for interleukin-1alpha (IL-1alpha), IL
      1beta, and interferon-gamma (IFN-gamma). The adsorption of cytokines by several
      different silica adsorbents was investigated. Increased concentrations of NaCl
      reduced cytokine adsorption, but did not completely eliminate adsorption even at
      high concentrations, suggesting that adsorption wads not entirely electrostatic
      in nature. Possible mechanisms of cytokine adsorption are discussed. Data for
      batch adsorption for TNF-alpha was used to estimate the minimum amount of silica
      required to treat septic shock. It was concluded that a silica adsorbent has a
      sufficiently high capacity to be used for hemoperfusion. Adsorption of myoglobin
      and cytochrome c was also investigated as possible marker proteins for future
      dynamic adsorption studies in hemoperfusion devices.

PMID- 18623019
TI  - Protein complexation with acrylic polyampholytes.
AB  - The interaction of dilute mixtures of proteins and ABC triblock methacrylic
      polyampholytes at different values of pH was investigated turbidimetrically. The
      onset of interaction was manifested by large changes in turbidity at certain
      critical pHs which lie close to the isoelectric points of the two interacting
      components. Protein precipitation yields in protein-polyampholyte binary mixtures
      followed the corresponding turbidity profiles and varied from 10% to 90%. The
      synthetic polyampholytes self-aggregate around their isoelectric point. The
      kinetics of precipitation of one of the same polymer with soybean trypsin
      inhibitor were studied, with turbidity-based characteristic times (exponential
      fit) of 2-3 min. The kinetics of precipitation of the protein-polymer mixture are
      slower than that of pure polymer because a small, but steady, long-term increase
      in turbidity is observed in the former case. The pH-dependence of the turbidity
      of binary mixtures of one protein and one synthetic polyampholyte, as well as a
      tertiary mixture of two proteins and one polyampholyte, were measured 30 min
      after the pH adjustment. The observations in these experiments along with the
      measured protein precipitation yields in the binary mixtures and the
      polyampholyte self-aggregation can be used for polymer removal and recycling. The
      latter constitutes a significant advantage over the use of homopolyelectrolytes
      which cannot easily be recycled.

PMID- 18623020
TI  - Soluble microbial products (SMP) in anaerobic chemostats.
AB  - The production of soluble microbial products (SMP) in anaerobic systems was
      evaluated using chemostat reactors. Results from steady-state and tracer
      experiments with (14)C-glucose and (14)C-acetate showed that significant amounts
      of SMP were produced during the acidogenesis of glucose, but that SMP did not
      accumulate during methanogenesis from acetate. In addition, at a retention time
      of 40 days, SMP comprised almost all of the effluent COD from the glucose-fed
      chemostat. For shorter retention times, as low as 10 days, the SMP concentration
      remained almost constant, but its significance in the effluent COD was reduced
      due to the accumulation of intermediate volatile fatty acids. The results from a
      (14)C-tracer experiment in the glucose-fed chemostat were used to evaluate the
      importance of including SMP formation and degradation in kinetic modeling of the
      methanogenic chemostats. Three models were evaluated: a model without SMP
      production, a model with SMP production but no degradation, and a model with SMP
      production and degradation, The results of this kinetic analysis indicate that
      the model that includes SMP production and degradation was the only one able to
      adequately represent the fate of (14)C in the tracer experiment. The kinetic
      parameters were successfully used to predict steady-state concentrations of SMP
      and to characterize the formation and degradation characteristics of the SMP.

PMID- 18623021
TI  - Characterization of compost biofiltration system degrading dichloromethane.
AB  - The effects of acclimatization of microbial populations, compound concentration,
      and media pH on the biodegradation of low concentration dichloromethane emissions
      in biofiltration systems was evaluated. Greater than 98% removal efficiency was
      achieved for dichloromethane at superficial velocities from 1 to 1.5 m(3)/m(3).
      min (reactor residence times of 1 and 0.7 min, respectively) and inlet
      concentrations of 3 and 50 ppm Although acclimatization of microbial populations
      to toluene occurred within 2 weeks of operation start-up, initial dichloromethane
      acclimatization took place over a period of 10 weeks. This period was shortened
      to 10 days when a laboratory grown consortium of dichloromethane degrading
      organism, isolated from a previously acclimatized column, was introduced into
      fresh biofilter media. The mixed culture consisted to 12 members, which together
      were able to degrade dichloromethane at concentrations up to 500 mg/L. Only one
      member of the consortium was able to degrade dichloromethane were sustained for
      more than 4 months in a biofilter column receiving an inlet gas stream with 3
      ppm(v) of dichloromethane acidification of the column and resulting decline in
      performance occurred when a 50-ppm(v) inlet concentration was used. A biofilm
      model incorporating first order biodegradation kinetics provided a good fit to
      observed concentration profiles, and may prove to be a useful tool for designing
      biofiltration systems for low concentration VOC emissions.

PMID- 18623022
TI  - Improvement of cloned alpha-amylase gene expression in fed-batch culture of
      recombinant Saccharomyces cerevisiae by regulating both glucose and ethanol
      concentrations using a fuzzy controller.
AB  - The effect of ethanol concentration on cloned gene expression in recombinant
      Saccharomyces cerevisiae strain 20B-12 containing one of two plasmids, pNA3 and
      pNA7, was investigated in batch cultures. Plasmids pNA3 and pNA7 contain the
      alpha-amylase gene under the control of the SUC2 or PGK promoter, respectively.
      When the ethanol concentration was controlled at 2 to 5 g/L, the gene expressions
      were two times higher than those at 20 g/L ethanol. The increase the gene
      expression by maintaining both the ethanol and glucose concentrations at low
      levels, a fuzzy controller was developed. The concentrations of glucose and
      ethanol were controlled simultaneously at 0.15 and 2 g/L, respectively, in the
      production phase using the fuzzy controller in fed-batch culture. The synthesis
      of alpha-amylase was induced by the low glucose concentration and maintained at a
      high level of activity by regulating the ethanol concentration at 2 g/L. The
      secretory alpha-amylase was induced by the low glucose concentration and
      maintained at a high level of activity by regulating the ethanol concentration at
      2 g/L. The secretory alpha-amylase activities of cells harboring plasmids pNA3
      and pNA7 in fed-batch culture were 175 and 395 U/mL, and their maximal specific
      activities 7.7 and 12.4 U/mg dry cells, respectively. These values are two to
      three times higher in activity and three to four times higher in specific
      activity than those obtained when glucose only was controlled.

PMID- 18623023
TI  - Adsorption and synergism of cellobiohydrolase I and II of Trichoderma reesei
      during hydrolysis of microcrystalline cellulose.
AB  - Hydrolysis of microcrystalline cellulose (Avicel) by cellobiohydrolase I and II
      (CBH I and II) from Trichoderma reesei has been studied. Adsorption and synergism
      of the enzymes were investigated. Experiments were performed at different
      temperatures and enzyme/substrate ratios using CBH I and CBH II alone and in
      reconstituted equimolar mixtures. Fast protein liquid chromatography (FPLC)
      analysis was found to be an accurate and reproducible method to follow the enzyme
      adsorption. A linear correlation was found between the conversion and the amount
      of adsorbed enzyme when Avicel was hydrolyzed by increasing amounts of CBH I
      and/or CBH II. CBH I had lower specific activity compared to CBH II although,
      over a wide concentration range, more CBH I was adsorbed than CBH II. Synergism
      between the cellobiohy-drolases during hydrolysis of the amorphous fraction of
      Avicel showed a maximum as a function of total enzyme concentration. Synergism
      measured as a function of bound enzyme showed a continuous increase, which
      indicates that by decreasing the distance between the two enzymes the synergism
      is enhanced. The adsorption process for both enzymes was slow. Depending on the
      enzyme/substrate ratio it took 30-90 min to reach 95% of the equilibrium binding.
      The amount of bound enzyme decreased with increasing temperature. The two enzymes
      compete for the adsorption sites but also bind to specific sites. Stronger
      competition for adsorption sites was shown by CBH I.

PMID- 18623024
TI  - Efficient specific release of periplasmic proteins from Escherichia coli using
      temperature induction of cloned kil gene of pMB9.
AB  - We have cloned the kil gene of pMB9 under control of the tightly regulated
      leftward promoter (pL) of coliphage lambda. Three types of plasmids were
      constructed. In all cases the activity of the lambda promoter is controlled by a
      thermosensitive cl repressor (product of the c/857 gene) supplied form a resident
      defective prophage or cloned onto a compatible p 15A-derived plasmid. Induction
      of the kil protein is brought about by a temperature shift of the culture from 28
      degrees C to 42 degrees C. Plasmid pPLc28K1 contains the kil gene including its
      natural ribosome-binding site and preceded by a transcription termination site.
      Using a bacterial strain with antitermination properties (e.g., M5219),
      periplasmic proteins can upon induction be gradually the growth of the host
      strain. The second plasmid pPLc321K1, contains the kil-coding sequence preceded
      by an engineered ribosome binding site derived from the attenuator of the
      Escherichia coli tryptophan operon. With this plasmid induction of the Kil
      protein is very rapid and specific release of the periplasmic proteins in
      essentially complete within 30 min after induction. In a third construct,
      pcl857K1, the pL-kil cassette together with c/857 allele are present on the same
      replicon, which is compatible with ColE1-derived expression vectors. This
      configuration allows accumulation in the periplasm of cloned gene products,
      induced by, e.g., tac or trp promoters at low temperature and subsequent release
      into the medium following increase of the temperature of the culture. Under
      repressed conditions (growth at low temperature) all plasmids are perfectly
      stable in a large number of E. coli strains tested, also when cultivated on a 20
      L fermentor scale. Controlled, heat-induced release of periplasmic proteins is
      highly specific and applicable at relatively high cell densities. The method
      therefore is an attractive alternative to cumbersome osmotic shock procedures for
      large-scale cultures.

PMID- 18623025
TI  - Immobilization of "Disguised" yeast in chemically crosslinked chitosan beads.
AB  - A new simple method for the preparation of chemically crosslinked chitosan beads
      is presented. It consists of the dropwise addition of 2-3% (w/v) low molecular
      weight chitosan solution containing 2% (w/v) glyoxal in 1% (w/v)
      tetrasodiumdiphosphate, pH 8.0. Immobilized viable baker's yeast (Saccharomyces
      cerevisiae) could be obtained via gel entrapment within the new beads when means
      preventing their direct contact with soluble chitosan were provided, "disguising"
      the cells until gelation and crosslinking were completed. Such means included
      cell suspension in castor oil or mixing with carboxymethyl-cellulose powder.
      Application of these means was shown to be necessary, as cells exposed to soluble
      chitosan immediately lost their viability and glycolytic activity. Yeast
      disguised in castor oil was also protected from bead reinforcement by
      glutaraldehyde treatment, significantly strengthening bead stability while
      operating under acidic conditions. This capability was demonstrated by continuous
      ethanol production by chitosan entrapped yeast.

PMID- 18623026
TI  - Flow parameters associated with hydrodynamic cell injury.
AB  - Two flow parameters are proposed for the analysis of flows that have potential to
      damage animal cells. They are the state of stress (characterized by the second
      invariant of the stress tensor) and the flow classification parameter R(D) (which
      is related to the possibility of stress relaxation). We consider the flow that
      occurs when a 1.7-mm bubble collapses at a liquid interface. Using these two
      parameters, we show the regions in which the flow is strong in terms of high
      hydrodynamic stresses and elongation characteristics.

PMID- 18623027
TI  - Enhancement of monoclonal antibody yield by hybridoma fed-batch culture,
      resulting in extended maintenance of viable cell population.
AB  - Hybridoma batch cultures were extended using feed formulations based on nutrient
      consumption measured during different batch culture phases when (a) growth but
      negligible antibody production was taking place; (b) maximum antibody production
      rate and declining viable cell growth rate were observed. Strategy (a) was the
      more successful (2.8-fold compared with 1.8-fold antibody titer increase) and
      maintained cell viability for longer. Analysis of the effects of omitting
      individual amino acids yielded results which were consistent with those from the
      feeding experiment.

PMID- 18623028
TI  - Use of respiratory quotient as a control parameter for optimum oxygen supply and
      scale-up of 2,3-butanediol production under microaerobic conditions.
AB  - The respiratory quotient (RQ) was found to be a suitable control parameter for
      optimum oxygen supply for the production of 2,3-butanediol + acetoin under
      microaerobic conditions. In laboratory scale continuous cultures optimum
      production of 2,3-butanediol + acetoin was obtained at an RQ value between 4.0 to
      4.5. This agreed well with optimum RQ value (4.0) stoichiometrically derived from
      the bioreactions involved. In fed-batch cultures product concentrations as high
      as 102.9 g/L (96.0 g/L butanediol + 6.9 g/L acetoin) can be achieved within 32 h
      cultivation with an RQ control algorithm for oxygen supply. Under similar
      conditions only 85.7 g/L product (77.6 g/L butanediol + 8.1 g/L acetoin) was
      obtained with control of constant oxygen supply rate throughout the
      cultivation.In pilot scale batch cultures under identical oxygen supply rate the
      achievable RQ value was found to be strongly influenced by the reactor type and
      scale. The initial oxygen supply rate influenced the achievable RQ as well.
      However, in all the reactors studied the specific product formation rate of cells
      in the exponential growth phase was only a function of RQ. The same optimum RQ
      value as found in continuous cultures was obtained. It was thus concluded that RQ
      can be used as a control parameter for optimum production of 2,3-butanediol +
      acetoin in both laboratory and pilot plant scale reactors.

PMID- 18623029
TI  - Enhancement of oxygen transfer in highly viscous non-newtonian fermentation
      broths.
AB  - The influence of short draft tubes covered by perforated plates on gas-liquid
      mass transfer was examined in external-loop airlift bioreactors. The volumetric
      mass transfer coefficients in a model external-loop airlift bioreactor were
      measured with water and non-Newtonian media. It was found that introduction of
      draft tubes covered with perforated plates in the riser significantly improved
      the mass transfer rate, particularly in higher viscous non-Newtonian fermentation
      media. The enhancement of mass transfer rate might be due mainly to an increase
      in bubble coalescence and redispersion.

PMID- 18623030
TI  - Saccharification, fermentation, and protein recovery from low-temperature AFEX
      treated coastal bermudagrass.
AB  - Coastal bermudagrass was pretreated by a low-temperature ammonia fiber explosion
      (AFEX) process, which soaked the grass in liquid ammonia and then explosively
      released the pressure. Saccharifying enzymes were systematically applied to the
      AFEX-treated grass corresponding to low, medium, and high loadings of
      cellulase/hemicellulase (from Trichoderma reesei), cellobiase, glucoamylase, and
      pectinase. Three-day sugar yields linearly correlated with the logarithm of the
      cellulase loading. Supplemental enzymes (cellobiase, pectinase) caused upward
      shifts in the lines. The linearity and upward shifts are consistent with the HCH
      1 model of cellulose hydrolysis. The hydrolysis sugars were converted to ethanol
      using yeast (Saccharomyces cerevisiae). The solid residues were treated with
      proteases to attempt recovery of valuable proteins. The low-temperature AFEX
      pretreatment was able o nearly double sugar yields. At the highest cellulase
      loadings (30 IU/g), the best reducing sugar and ethanol yields were 53% and 44%
      of the maximum potential, respectively. Protein recovery was, at most, 59%.

PMID- 18623031
TI  - Use of plant material for the decontamination of water polluted with phenols.
AB  - Plant materials were found useful in the decontamination water polluted with
      phenolic contained in the plant tissue. The enzymes mediated oxidative coupling
      of the pollutants, followed by precipitation of the formed polymers from the
      aqueous phase. An industrial wastewater contaminated with 2,4-dichlorophenol (up
      to 850 ppm) and other chlorinated phenols was successfully treated using minced
      horseradish, potato, or white radish (amended with H(2)O(2)). Horseradish
      mediated removal of 2,4-dichlorophenol from model solutions was comparable with
      that achieved using purified horseradish peroxidase. In addition, horseradish
      could be reused up to 30 times. Due to the apparent ease of application, the use
      of plat material may present a breakthrough in the enzyme treatment of
      contaminated water.

PMID- 18623032
TI  - Induction of apoptosis in nutrient-deprived cultures of hybridoma and myeloma
      cells.
AB  - In the present study, cell death was investigated in cultures of NS/0 myelomas
      and SP2/0-derived D5 hybridomas through morphological examination of cells
      stained with acridine orange and ethidium bromide. The relative contribution of
      elevated levels of lactic acid and ammonia, as well as deprivation of glutamine,
      cystine, and glucose on the induction of necrosis or apoptosis, was investigated.
      In batch culture of D5 hybridoma cells, induction of apoptotic cell death
      correlated with the exhaustion of glutamine, while in the case of NS/0 myelomas,
      it coincided with exhaustion of cystine. To determine whether limiting nutrients
      were the actual triggering factors for apoptosis in batch culture, exponentially
      growing cells were resuspended in glutamine or cystine-free media. Within 30 to
      40 h, viability decreased to 50% and the nonviable cell population displayed
      typical apoptotic morphology, with crescents of condensed chromatin around the
      periphery of the nucleus, or with the entire nucleus present as one or a group of
      featureless, brightly staining spherical beads. Similarly, D5 hybridomas and NS/0
      myelomas cultivated in glucose-free medium died mainly from apoptosis. Cells were
      also cultivated in fresh medium supplemented with elevated concentrations of
      ammonia (3.0 mM) and/or lactate (35 mM, 50 mM). This resulted in decreased
      viabilities and necrotic death in both cell lines. From these results, we
      conclude that D5 hybridomas and NS/0 myelomas deprived of essential nutrients die
      by apoptosis, whereas incubation in the presence of elevated levels of metabolic
      byproducts such as ammonia and lactate will induce necrotic cell death in these
      cells.

PMID- 18623033
TI  - Physiological responses of hybridoma cells in a protein-free medium to soluble
      and immobilized antigen.
AB  - This study examined the effect of antigen in a protein free medium on cell growth
      and monoclonal antibody production by a hybridoma line. Antigen immobilized on a
      Sepharose gel matrix via a bovine gamma-globulin carrier protein was used to
      stimulate the cell cultures in T-flasks. In comparison to antigen-free culture,
      total antibody production during was increased up to 40%, while slower cell
      growth rates were observed. The specific antibody production during the
      stationary culture phase was 40% to 80% higher in the presence of immobilized
      antigen. The surface density of antigen on the Sepharose beads had a strong
      influence on the physiological response of the hybridomas.

PMID- 18623035
TI  - Juvenile nasopharyngeal angiofibroma: clinical factors associated with recurrence
      and proposal of a staging system.

PMID- 18623036
TI  - More options and improved outcomes for hepatocellular carcinoma.

PMID- 18623037
TI  - Alf Ketcham and his Italian friends.

PMID- 18623038
TI  - Juvenile nasopharyngeal angiofibroma: clinical factors associated with
      recurrence, and proposal of a staging system.
AB  - BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a vascular tumor of the
      nasopharynx. Our aim is to analyze prognostic factors, report results obtained
      with radiation therapy and propose a staging system. MATERIALS AND METHODS:
      Retrospective study of patients with JNA. Clinical, radiological and therapeutic
      data were assessed for recurrence- and disease free survival-associated
      prognostic factors. Bivariate and multivariate analyses were performed. RESULTS:
      Fifty-four males were analyzed. Invasion to anterior infratemporal fossae (ITF)
      +/or to pterygomaxillary fossae, to posterior infratemporal fossae, or
      intracranial extension were associated with recurrences in 2 of 15, in 8 of 18,
      and in 8 of 12 cases, respectively. Tumors < or > or =6 cm were associated with
      zero and with 18 recurrences, respectively (P = 0.006). A staging system is
      constructed considering extension patterns and size. Multivariate analyses
      conferred significance (P = 0.002) to a model including this staging system and
      surgical margins. CONCLUSION: Our system stratifies recurrence risk and disease
      free survival efficiently. Since radiotherapy at young age has potential to
      induce malignancies, it should be used with caution. It could be considered as
      primary treatment in stage IV cases with major invasion to cavernous sinus or
      orbital apex. Therapy design may be improved.

PMID- 18623039
TI  - Changing management and outcome of hepatocellular carcinoma: evaluation of 501
      patients treated at a single comprehensive center.
AB  - BACKGROUND: We evaluated changes in therapy and outcome for patients with
      hepatocellular carcinoma (HCC) over time in a large cohort of Western patients
      managed at one U.S. medical center. METHODS: A retrospective analysis of all
      patients with HCC treated at one U.S. medical center was performed. Analyses were
      stratified by time intervals 1990-1996 (pre-Milan) and 1997-2004 (post-Milan) to
      examine impact of UNOS criteria adapted from the post-Milan experience with OLT
      on treatment and survival. RESULTS: From 1990 to 2004, 501 patients were
      identified, 170 (34%) pre-Milan and 331 (66%) post-Milan. Seventy-four (15%)
      underwent OLT, 99 (20%) had partial hepatectomy (PH), 51 (10%) had ablative
      therapy (Ablate), 84 (16%) had embolic treatment (Embo), and 194 (39%) had
      chemotherapy or supportive care (C/SC). Median survival for all patients was 11
      months. By time interval, median overall survival (OS) was better for post-Milan
      patients as compared with the pre-Milan group (13 months vs. 7 months, P = 0.02).
      On multivariate analysis OLT had the strongest association with improved survival
      of all factors examined (Odds ratio 12.4, 95% CI 7.7-20.5). CONCLUSIONS: In this
      series, treatment post-1996 is associated with improved survival, likely due to
      improvements in selection criteria and outcomes for liver transplantation.

PMID- 18623041
TI  - Automated determination of precursor ion, product ion, and neutral loss
      compositions and deconvolution of composite mass spectra using ion correlation
      based on exact masses and relative isotopic abundances.
AB  - After an accidental, deliberate, or weather-related dispersion of chemicals
      (dispersive event), rapid determination of elemental compositions of ions in mass
      spectra is essential for tentatively identifying compounds. A direct analysis in
      real time (DART)ion source interfaced to a JEOL AccuTOFmass spectrometer provided
      exact masses accurate to within 2 mDa for most ions in full scan mass spectra and
      relative isotopic abundances (RIAs) accurate to within 15-20% for abundant
      isotopic ions. To speed determination of the correct composition for precursor
      ions and most product ions and neutral losses, a three-part software suite was
      developed. Starting with text files of m/z ratios and their ion abundances from
      mass spectra acquired at low, moderate, and high collision energies, the ion
      extraction program (IEP) compiled lists for the most abundant monoisotopic ions
      of their exact masses and the RIAs of the +1 and +2 isotopic peaks when abundance
      thresholds were met; precursor ions; and higher-mass, precursor-related species.
      The ion correlation program (ICP) determined if a precursor ion composition could
      yield a product ion and corresponding neutral loss compositions for each product
      ion in turn. The input and output program (IOP) provided the ICP with each
      precursor ion:product ion pair for multiple sets of error limits and prepared
      correlation lists for single or multiple precursor ions. The software determined
      the correct precursor ion compositions for 21 individual standards and for three-
      and seven-component mixtures. Partial deconvolution of composite mass spectra was
      achieved based on exact masses and RIAs, rather than on chromatography.

PMID- 18623040
TI  - Pharmacokinetics of budesonide and formoterol administered via a series of single
      drug and combination inhalers: four open-label, randomized, crossover studies in
      healthy adults.
AB  - OBJECTIVE: To investigate the pharmacokinetics of budesonide and formoterol
      administered concomitantly in healthy adults. METHODS: Three single-dose, open
      label crossover studies (n=28 each) were conducted (Study I: budesonide pMDI,
      formoterol DPI, budesonide pMDI+formoterol DPI; Study II: budesonide/formoterol
      pMDI, budesonide pMDI+formoterol DPI; Study III: budesonide/formoterol pMDI
      [three budesonide formulation strengths; constant formoterol]). Study IV (n=28)
      assessed steady state pharmacokinetics (budesonide/formoterol pMDI [two/four
      inhalations twice daily, 5-day treatment; four inhalations, single-dose]).
      RESULTS: Study I: no pharmacokinetic interactions were observed between
      budesonide and formoterol. Study II: AUC ratios were 97.9% (budesonide) and 82.2%
      (formoterol) (budesonide/formoterol pMDI versus budesonide pMDI+formoterol DPI).
      Study III: formoterol AUC was comparable across budesonide/formoterol pMDI
      formulation strengths; budesonide AUC increased with formulation strength in
      proportion to fine particle dose. Study IV: dose proportionality was demonstrated
      for budesonide (AUC ratio, 104.3%) and suggested for formoterol (AUC ratio,
      117.6%) with budesonide/formoterol pMDI (steady state); budesonide and formoterol
      AUC was higher with repeated versus single-dose budesonide/formoterol pMDI (four
      inhalations). CONCLUSIONS: No pharmacokinetic interactions were observed between
      budesonide and formoterol. Budesonide dose variation in budesonide/formoterol
      pMDI did not affect formoterol exposure. Steady state budesonide/formoterol pMDI
      dose-doubling yielded proportional increases in budesonide and formoterol
      exposure.

PMID- 18623042
TI  - Kidney volume quantification using contrast-enhanced in vivo X-ray micro-CT in
      mice.
AB  - The present study sought to establish a standard in vivo imaging procedure for
      mouse kidney anatomy evaluation using contrast-enhanced high-resolution X-ray
      microtomography (micro-CT). Micro-CT estimation of kidney volume was compared
      with ex vivo measurement by micro-CT and water displacement. Control values were
      obtained in four strains (BALB/c, C3H/HeN, 129/Sv and C57BL/6J) of healthy male
      and female mice aged 22 +/- 2 weeks. An excellent correlation was found between
      in vivo and ex vivo kidney volumes (n = 26 mice; 52 kidneys; r = 0.96). In vivo
      measurement systematically overestimated ex vivo kidney volume by 28 +/- 4%,
      while there was no significant difference between the ex vivo micro-CT value and
      the true kidney volume on water displacement (2.3 +/- 2.1%). In vivo kidney
      volume also correlated strongly with kidney weight and in vivo kidney length (n =
      52 mice; 104 kidneys; r = 0.84, r = 0.92 respectively). Differences between
      strains were observed for kidney volume when comparing either kidney volume or
      kidney weight to body weight. In conclusion, this study demonstrated that
      contrast-enhanced micro-CT enables accurate in vivo measurement of kidney volume,
      length and thickness in mice. Reference parameters are reported for four strains.
      The technique provides a useful follow-up research tool for mouse phenotyping and
      renal disease studies.

PMID- 18623043
TI  - Evaluation of gender in the oral pharmacokinetics of clindamycin in humans.
AB  - Clindamycin is an antimicrobial agent metabolized by CYP3A4. Gender may influence
      the pharmacokinetics of drugs metabolized by this pathway, however, no
      information about differences in the pharmacokinetics of clindamycin in men and
      women is available. The purpose of this study was to evaluate gender differences
      in clindamycin oral pharmacokinetics. Twenty-four subjects (11 men and 13 women)
      received an oral 600 mg dose of clindamycin under fasting conditions and plasma
      concentrations were obtained at selected times during 12 h. Increased plasma
      levels were observed in women, but when the dose was normalized by the body
      weight of individuals, these differences disappeared, indicating that gender does
      not play an important role in the pharmacokinetics of this drug.

PMID- 18623045
TI  - Effects of diffusion limitation on immobilized nitrifying microorganisms at low
      temperatures.
AB  - Activation energies of suspended and immobilized nitrifying bacteria were
      determined and compared to determine if diffusion limitation results in decreased
      sensitivity for temperature. The activation energy for the respiration activity
      of suspended Nitrosomonas europaea and Nitrobacter agilis was found to be 86.4
      and 58.4 kJ mol(-1), respectively. The activation energy for oxygen diffusion in
      the support material, kappa-carrageenan, determined from the effect of
      temperature on the effective diffusion coefficient (D), was 17.2 kJ mol(-1).
      Consequently, the apparent actvation energy of diffusion limited cells should be
      lower. It was indeed shown that due to the effect of diffusion limitation and to
      temperature effects on the Monod constant K(s), the immobilized-cell activity was
      less sensitive to temperature. The apparent activation energy for immobilized Ns.
      europaea was between 28.6 and 94.2 kJ mol(-1) and for immobilized Nb. agilis
      between 1.4 and 72.9 kJ mol(-1), depending on the oxygen concentration and
      temperature. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623046
TI  - Synthesis of protein-containing polymers in organic solvents.
AB  - Subtilisin has been modified with polyethylene glycol (PEG) monomethacrylate (MW
      8000) by reductive alkylation, and incorporated into polymethyl methacrylate
      durring free-radical initiated polymerization. The activity and stability of the
      PEG-modified enzymes have been determined in aqueous buffer and organic solvents.
      The K(m) and V(max) values for unmodified, singly and doubly modified subtilisin
      were compared in these environments, and the half-lives of both modified enzymes
      were remarkably high (up to 2 months). The protein-containing polymer was
      analyzed for activity and polymer properties, and our results indicate that
      active subtilisin can be incorporated into polymethyl methacrylate during
      polymerization in organic solvents while retaining its activity and stability.
      (c) 1995 John Wiley & Sons, Inc.

PMID- 18623047
TI  - Correlation between steady-state cell concentration and cell death of hybridoma
      cultures in chemostat.
AB  - In the present study, the steady-state cell density (X) of chemostat cultures of
      murine hybridoma was varied by the concentration of glucose and glutamine in
      culture medium and the dissolved oxygen partial pressure. Except at low glutamine
      and low oxygen levels, the specific death rate (k(d)) of the cultures was found
      to decrease with increasing dilution rate (D). However, the plot of k(d) vs. X/D
      yielded linear relation, which suggests that cell death was due to a non-growth
      linked inhibitory product of the cells. The k(d) value measured at low glutamine
      and low oxygen levels remained practically unchanged over a wide range of D
      between 0.020 and 0.029 h(-1). The k(d) for low oxygen cultures was always lower
      than the values obtained in low glucose and low glutamine cultures. A low
      molecular-weight component of possibly less than 3000 MW was detected to be cell
      death-inducing in the supernatant of exponentially growing cultures. It was
      neither lactate nor ammonium. The autoinhibitor was not cell-line specific. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623048
TI  - Enzymatic interesterification of triglyceride with surfactant-coated lipase in
      organic media.
AB  - Several surfactant-coated enzymes have been prepared by coating lipases of
      various origins with a nonionic surfactant, glutamic acid dioleylester ribitol
      (2C(18)Delta(9)GE). Enzymatic interesterification of tripalmitin with oleic acid
      using the surfactant-coated lipase was carried out in organic media. The
      surfactant-coated lipases could effectively catalyze the interesterification of
      glycerides better than did the powder lipases. A suitable organic solvent was an
      aliphatic hydrocarbon such as isooctane. The enzymatic activity for the
      interesterification strongly depended on the origin of the lipase. The surfactant
      coated lipase prepared by Mucor javanicus showed the highest enzymatic activity
      for the interesterification of glycerides, although its powder lipase did not
      show enzymatic activity. Selective interesterification of glycerides could be
      performed by adjusting the concentration ratio of oleic acid to tripalmitin in
      isooctane. Di-substituted glyceride could be selectively produced when the
      concentration ratio of carboxylic acid to glycerides was 7. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623049
TI  - Catalytic behavior of Pseudomonas cepacia lipase in w/o microemulsions.
AB  - The activity of purified Pseudomonas cepacia lipase has been investigated in
      esterification reactions of various aliphatic alcohols with natural fatty acids.
      The reactions were carried out in microemulsions formed in isooctane by bis-(2
      ethylhexyl)sulfosuccinate sodium salt (AOT). Kinetic studies showed that the
      reaction follows a ping-pong bi-bi mechanism with inhibition by both substrates.
      The apparent kinetic parameters of the reaction were found to be K(m octanol) =
      310 mM, K(m lauric acid) = 78 mM, and V(max) = 250 mumol min(-1) mg(-1). The same
      system was used for the synthesis of mono- and diglycerides from glycerol and
      lauric acid, which was successful at very low w(o) values. The catalytic behavior
      of P. cepacia lipase was also studied in esterification reactions performed in a
      nonionic microemulsion system formulated by tetraethyleneglycoldodecylether
      (C(12)E(4)). The optimum activity was found at about w(o) = 8. The apparent
      values of V(max app) and K(m app) for octanol were calculated and found to be 100
      mumol min(-1) mg(-1) and 76 mM, respectively. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623050
TI  - On-line gas analysis in animal cell cultivation: I. Control of dissolved oxygen
      and pH.
AB  - To monitor gas reaction rates in animal cell culture at constant dissolved oxygen
      concentration (DO) and constant pH it was necessary to develop improved control
      methods. Decoupling of both controllrs was obtained by manipulation of molar
      fractions of oxygen and carbon dioxide in the gas phase. Two pairs of DO and pH
      controllers were designed and tested both in simulation and exprimental runs. The
      first controller pair was developed for headspace aeration only, whereas the
      second controller pair was designed for bubble aeration using a microsparger and
      flushing the headspace with helium. pH was controlled by a conventional discrete
      PID controller in its velocity form. For DO control two linear state space
      feedback controllers with parameter adaptation were established. In these
      controllers the oxygen uptake rate (OUR) was considered as a disturbance and was
      not included in the mathematical model. The feedback gain adaptation was based on
      the difference between the actual molar fraction of oxygen at time step n and the
      initial molar fraction. This difference is related to OUR and was used to
      increase or decrease the state feedback controller gain (k and k(1),
      respectively) in a slow manner. With these controllers it was possible to get an
      excellent online estimate of OUR. In the case of bubble aeration a simple gas
      phase mass balance was sufficient, whereas during the headspace aeration a liquid
      phase balance was required. It has been shown that determination of OUR using gas
      balance requires a significantly better controller performance compared to just
      keeping DO and pH within reasonable limits. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623051
TI  - On-line gas analysis in animal cell cultivation: II. Methods for oxygen uptake
      rate estimation and its application to controlled feeding of glutamine.
AB  - Different methods for oxygen uptake rate (OUR) determinations in animal cell
      cultivation were investigated using a high quality mass spectrometer. Dynamic
      measurements have considerable disadvantages because of disturbances of the
      growing cells by the necessary variations of dissolved oxygen concentration. Only
      infrequent discrete measurements are possible using this method. Stationary
      liquid phase balance yielded better results with much higher frequency. Gas phase
      balancing has the advantage of not requiring dissolved oxygen measurement and
      knowledge of K(L)a, both of them are easily biased. It was found that simple gas
      phase balancing is either very inaccurate (error larger than expected signal) or
      very slow, with gas phase residence times of several hours. Therefore, a new
      method of aeration was designed. Oxygen and CO(2) transfer are mainly achieved
      via sparging. The gas released to the headspace is diluted with a roughly 100
      fold stream of an inert gas (helium). Through this dilution, gas ratios are not
      changed for O(2), CO(2), Ar, and N(2). The measurement of lower concentrations
      (parts per million and below) is easy using mass spectrometry with a secondary
      electron multiplier. With this new method an excellent accuracy and sufficient
      speed of analysis were obtained. All these on-line methods for OUR measurement
      were tested during the cultivation of animal cells. The new method allowed better
      study of the kinetics of animal cell cultures as was shown with a hybridoma cell
      line (HFN 7.1, ATCC CRL 1606) producing monoclonal antibodies against human
      fibronectin. With the aid of these methods it was possible to find a correlation
      between a rapid decrease in oxygen uptake rate (OUR) and glutamine concentration.
      The sudden decrease in OUR can be attributed to glutamine depletion. This
      provided a basis for the controlled addition of glutamine to reduce the formation
      of ammonia produced by hydrolysis. This control method based on OUR measurement
      resulted in increased cell concentration and threefold higher product
      concentration. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623052
TI  - An in situ dissolved-hydrogen probe for monitoring anaerobic digesters under
      overload conditions.
AB  - The concentration of diatomic hydrogen in the liquid phase of an anaerobic
      digester was used to determine the onset of digester failure induced by substrate
      overloading. The construction of an inexpensive probe to measure dissolved
      hydrogen, having a partial pressure detection limit of 30 Pa, is described. An
      increase in the partial pressure of dissolved hydrogen, from less than 30 Pa to
      400 Pa, was observed when the D-glucose concentration in a laboratory-scaled
      digester was increased rapidly to 10 mM. However, when the digester was gradually
      overloaded, an increase in the dissolved-hydrogen partial pressure was not
      observed until after the digester failed. The accumulation of volatile fatty
      acids and digester failure were observed at dissolved-hydrogen partial pressures
      below 30 Pa. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623053
TI  - Parametric sensitivity of stoichiometric flux balance models applied to wild-type
      Escherichia coli metabolism.
AB  - Stoichiometrically based flux balance models provide a method to quantify the
      metabolic pathway fluxes within a living cell. Predictions of flux balance models
      are expected to have applications in pathway engineering as well as in bioprocess
      design and control. These models utilize optimality principles applied to
      metabolic pathway stoichiometry along with the metabolic requirements for growth
      to determine the flux distribution in a metabolic network. A flux balance model
      has been developed for Escherichia coli W3110 using five experimentally
      determined strain-specific parameters. In this report, we determine the
      sensitivity of the predictions of the flux balance model to these five strain
      specific parameters. Model predictions are shown to be sensitive to the two
      parameters describing metabolic capacity, while they are relatively insensitive
      to the three parameters that describe the metabolic requirements for growth.
      Thus, when stoichiometrically based models are formulated for additional strains
      one needs to measure the metabolic capacity (maximum rates of nutrient and oxygen
      utilization) accurately. Determination of metabolic capacity from batch
      experiments is relatively easy to perform. On the other hand, the harder to
      determine maintenance parameters need not be as accurately determined. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623054
TI  - Rheologies and morphologies of three actinomycetes in submerged culture.
AB  - The broth rheologies and morphologies of three actinomycetes (Saccharopolyspora
      erythraea, Actinomadura roseorufa, and Streptomyces rimosus) in submerged culture
      have been examined. The rheology of all the broths became pseudoplastic as soon
      as significant growth occurred with the power law index, n, falling to 0.20 to
      0.25. The consistency index, K, rose with biomass concentration although in some
      instances it fell later in the fermentation. The mean main hyphal lengths of all
      cultures were in the range, 15 to 25 mum, and did not alter greatly even when
      large changes in K were occurring. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623055
TI  - Starvation-induced programmed death of hybridoma cells: Prevention by amino acid
      mixtures.
AB  - Association of the availability of nutrients with the phenomenon of programmed
      cell death-apoptosis-was investigated using hybridoma cells cultured in protein
      free medium under conditions of starvation, i.e., in RPMl-1640 medium diluted to
      50% with saline. Amino acid mixtures, such as MEM essential amino acids or MEM
      nonessential amino acids were found to prevent starvation death significantly
      when added to the diluted medium in 1 to 2 mM concentrations, the MEM vitamin
      mixture was ineffective, and glutamine displayed a moderate growth-supporting
      effect. The specific monoclonal antibody production rate in cultures supplemented
      with amino acid mixtures was strikingly low, whereas supplementation with
      glutamine alone or simultaneously with other amino acids resulted in a specific
      antibody production rate comparable with the rate observed in undiluted medium.
      (c) 1995 John Wiley & Sons, Inc.

PMID- 18623056
TI  - The Monod equation and mass transfer.
AB  - An alternative interpretation of the growth rate-substrate concentration
      dependence is presented. This is based on the assumption that the main factors
      affecting growth rate are transfer of substrate from the medium and the maximum
      growth velocity, which is that observed when no substrate limitations occur. This
      approach allows the approximate prediction of one of the two kinetic constants
      required, and may be of great use, especially for continuous cultures. It is the
      first attempt to provide a phenomenological explanation for the large variations
      observed in the values of the Monod constant, K(s), reported in the literature.
      (c) 1995 John Wiley & Sons, Inc.

PMID- 18623057
TI  - Separation of amino-acid enantiomers using Micellar-enhanced ultrafiltration.

PMID- 18623058
TI  - Flexible sigmoidoscopy and whole colonic imaging in the diagnosis of cancer in
      patients with colorectal symptoms.
AB  - BACKGROUND: The aim was to identify the patients with colorectal symptoms most
      likely to benefit from whole colonic imaging (WCI) to diagnose colorectal cancer
      and those for whom flexible sigmoidoscopy (FS) may be initially sufficient.
      METHODS: This prospective observational study (16 years) included 16 433 newly
      referred patients with symptoms or signs of colorectal cancer. RESULTS:
      Colorectal cancer was diagnosed in 946 patients (diagnostic yield 5.8 per cent),
      815 (86.2 per cent) in the rectum or sigmoid (distal) and 131 (13.8 per cent) in
      the proximal colon. Some 15 829 patients (96.3 per cent) presented with symptoms
      alone (without iron deficiency anaemia or abdominal mass). Of 787 cancers in
      these patients, 750 (95.3 per cent) were distal. The prevalence of proximal
      cancer above and below the age of 60 years was 0.4 per cent (33 of 8249) and 0.1
      per cent (four of 7580) respectively. Of 16 256 patients having FS, 5665 (34.8
      per cent) had WCI. Of the other 10 591, five subsequently presented with proximal
      cancers. FS missed ten (1.3 per cent) of 796 cancers. CONCLUSION: Patients with
      iron deficiency anaemia or a mass require WCI. However, in patients with symptoms
      alone, FS detects 95 per cent of cancers, and the diagnostic yield of WCI after
      FS is very low. Alternative management strategies need to be developed to avoid
      unnecessary investigations in this low-risk group.

PMID- 18623059
TI  - Genetic circuitry controlling motility behaviors of Myxococcus xanthus.
AB  - M. xanthus has a complex multicellular lifestyle including swarming, predation
      and development. These behaviors depend on the ability of the cells to achieve
      directed motility across solid surfaces. M. xanthus cells have evolved two
      motility systems including Type-IV pili that act as grappling hooks and a
      controversial engine involving mucus secretion and fixed focal adhesion sites.
      The necessity for cells to coordinate the motility systems and to respond rapidly
      to environmental cues is reflected by a complex genetic network involving at
      least three complete sets of chemosensory systems and eukaryotic-like signaling
      proteins. In this review, we discuss recent advances suggesting that motor
      synchronization results from spatial oscillations of motility proteins. We
      further propose that these dynamics are modulated by the action of multiple
      upstream complementary signaling systems. M. xanthus is thus an exciting emerging
      model system to study the intricate processes of directed cell migration.

PMID- 18623060
TI  - The core endodermal gene network of vertebrates: combining developmental
      precision with evolutionary flexibility.
AB  - Embryonic development combines paradoxical properties: it has great precision, it
      is usually conducted at breakneck speed and it is flexible on relatively short
      evolutionary time scales, particularly at early stages. While these features
      appear mutually exclusive, we consider how they may be reconciled by the
      properties of key early regulatory networks. We illustrate these ideas with the
      network that controls development of endoderm progenitors. We argue that this
      network enables precision because of its intrinsic stability, self propagation
      and dependence on signalling. The network enables high developmental speed
      because it is rapidly established by maternal inputs at multiple points. In turn
      these properties confer flexibility on an evolutionary time scale because they
      can be initiated in many ways, while buffering essential progenitor cell
      populations against changes in their embryonic environment on both evolutionary
      and developmental time scales. Although stable, these networks must be capable of
      rapid dissolution as cell differentiation progresses. While we focus on the core
      early endodermal network of vertebrates, we argue that these properties are
      likely to be general in early embryonic stem cell populations, such as mammalian
      ES cells.

PMID- 18623061
TI  - Flexibility and charge asymmetry in the activation loop of Src tyrosine kinases.
AB  - Regulated activity of Src kinases is critical for cell growth. Src kinases can be
      activated by trans-phosphorylation of a tyrosine located in the central
      activation loop of the catalytic domain. However, because the required exposure
      of this tyrosine is not observed in the down-regulated X-ray structures of Src
      kinases, transient partial opening of the activation loop appears to be necessary
      for such processes. Umbrella sampling molecular dynamics simulations are used to
      characterize the free energy landscape of opening of the hydrophilic part of the
      activation loop in the Src kinase Hck. The loop prefers a partially open
      conformation where Tyr416 has increased accessibility, but remains partly
      shielded. An asymmetric distribution of the charged residues in the sequence near
      Tyr416, which contributes to shielding, is found to be conserved in Src family
      members. A conformational equilibrium involving exchange of electrostatic
      interactions between the conserved residues Glu310 and Arg385 or Arg409 affects
      activation loop opening. A mechanism for access of unphosphorylated Tyr416 into
      an external catalytic site is suggested based on these observations.

PMID- 18623062
TI  - Discovery of sarcosine dimethylglycine methyltransferase from Galdieria
      sulphuraria.
AB  - An enzyme with sarcosine dimethylglycine methyltransferase (SDMT) activity has
      been identified in the thermophilic eukaryote, Galdieria sulphuraria. The crystal
      structure of the enzyme, solved to a resolution of 1.95 A, revealed a fold highly
      similar to that of mycolic acid synthases. The kcat and apparent K(M) values were
      64.3 min(-1) and 2.0 mM for sarcosine and 85.6 min(-1) and 2.8 mM for
      dimethylglycine, respectively. Apparent K(M) values of S-adenosylmethionine were
      144 and 150 microM for sarcosine and dimethylglycine, respectively, and the
      enzyme melting temperature was 61.1 degrees C. Modeling of cofactor binding in
      the active site based on the structure of methoxy mycolic acid synthase 2
      revealed a number of conserved interactions within the active site.

PMID- 18623063
TI  - Identification and characterization of folding inhibitors of hen egg lysozyme: an
      example of a new paradigm of drug design.
AB  - Studies of protein folding indicate the presence of native contacts in the
      denatured state, giving rise to folding elements which contribute to the
      accomplishment of the native state. The possibility of finding molecules which
      can interact with specific folding elements of a target protein preventing it
      from reaching its native state, and hence from becoming biologically active, is
      particularly attractive. The notion that folding elements not only provide
      molecular recognition directing the folding process, but also have conserved
      sequence, implies that targeting such elements will make protein folding
      inhibitors less susceptible to mutations which, in many cases, abrogate drug
      effects. The folding-inhibition strategy can lead to a truly novel and rational
      approach to drug design, aside from providing new insight into folding. This is
      illustrated in the case of hen egg lysozyme.

PMID- 18623064
TI  - The crystal structure of the ING5 PHD finger in complex with an H3K4me3 histone
      peptide.

PMID- 18623065
TI  - Structure of HP0564 from Helicobacter pylori identifies it as a new
      transcriptional regulator.

PMID- 18623066
TI  - Chronic bioassay in benthic fish for the assessment of the quality of sediments
      in different areas of the coast of Spain impacted by acute and chronic oil
      spills.
AB  - More and more, the coastal regions of the world suffer from the contamination of
      petroleum hydrocarbon [principally polycyclic aromatic hydrocarbons (PAHs)]. This
      contamination can be acute, as it happened in the Coast of Galicia (NW, Spain) by
      the oil spill from a tanker, or chronic by the existence of high maritime traffic
      and a lot of industries as it is the case of the Bay of Algeciras (BA) (SW,
      Spain). It is of a great concern due to the toxicity, especially in sediments and
      ecosystem associated to it. The objective of this study is to assess, through
      chronic bioassay, sediment toxicity in samples collected in different littoral
      areas of Spain and to compare the damage caused in benthic fish, Solea
      senegalensis, according to that which suffers acute spill (Coast of Galicia) or
      chronic spill (the BA) by means of histopathology methods and enzymatic
      activities studies. Organisms were exposed to different sediments from Galician
      Coast and the BA during 42 days and every sample was analyzed by triplicate in
      glass aquaria. At the end of the bioassay, histopathological diseases were
      analyzed in the gills, target organ. Likewise, stress parameters as
      ethoxyresorufin-O-deethylase (EROD) and the glutathione S-transferases (GSTs)
      activities were determined in the liver. Results showed a significant positive
      correlation between the biomarkers of exposure (EROD and GST), biomarkers of
      effect (histopathology), and PAHs concentrations in the sediments.

PMID- 18623067
TI  - Fungal sex genes-searching for the ancestors.
AB  - The sex-determining genes of fungi reside at one or two specialised regions of
      the chromosome known as the mating type (MAT) loci. The genes are sufficient to
      determine haploid cell identity, enable compatible mating partners to attract
      each other, and prepare cells for sexual reproduction after fertilisation. How
      conserved are these genes in different fungal groups? New work1 seeks an answer
      to this question by identifying the sex-determining regions of an early diverged
      fungus. These regions bear remarkable similarity to those described in other
      fungi, but the sex proteins they encode belong to only a single class of
      transcription factor, the high mobility group (HMG), indicating that these are
      likely to be ancestral to other proteins recruited for fungal sex.

PMID- 18623068
TI  - Cohesin and CTCF: cooperating to control chromosome conformation?
AB  - The cohesin complex is best known for its role in sister chromatid cohesion. Over
      the past few years, it has become apparent that cohesin also regulates gene
      expression, but the mechanisms by which it does so are unknown. Recently, three
      groups mapped numerous cohesin-binding sites in mammalian chromosomes and found
      substantial overlap with the CCCTC-binding factor (CTCF).1-3 CTCF is an insulator
      protein that blocks enhancer-promoter interactions, and the investigators found
      that cohesin also contributes to this activity. Thus, these studies demonstrate
      at least one mechanism by which cohesin can control gene expression.

PMID- 18623069
TI  - Tumorigenesis and neurodegeneration: two sides of the same coin?
AB  - Dysregulation of genes that control cell-cycle progression and DNA repair is a
      hallmark of tumorigenesis. It is becoming increasingly apparent, however, that
      these defects also contribute to degeneration of post-mitotic neurons under
      certain conditions. The gene for ataxia-telangiectasia mutated (ATM) is a
      prototype for this dual mechanism of action, with loss-of-function mutations
      causing not only selective degeneration of cerebellar neurons but also increased
      susceptibility to breast cancer and hematologic malignancy. Increased dosage of
      amyloid precursor protein in Down syndrome (trisomy 21) predisposes to dementia
      of Alzheimer type and may also contribute to acute leukemia and transient
      myeloproliferative disorder. The gene parkin, loss-of-function mutations in which
      account for about half of cases of early-onset Parkinson disease, has been
      identified as a candidate tumor suppressor gene by several groups. Parkin is
      deleted or downregulated in several tumor types, and its re-expression sensitizes
      derivative cell lines to inhibitors of cell-cycle progression. The overlap of
      molecular pathways implicated in cancer and neurodegeneration challenges long
      held notions about differentiated cellular states and may open the door to novel
      therapeutic approaches to both groups of disorders.

PMID- 18623070
TI  - The many faces of telomerase: emerging extratelomeric effects.
AB  - Telomeres, the ends of chromosomes, shorten with each cell division. To expand
      their replicative potential, various cell types use the ribonucleoprotein
      telomerase, which lengthens telomeres by its reverse transcriptase activity.
      Because of its ability to immortalize cancer cells, telomerase also plays a
      significant role in tumor growth. However, in recent years, a wide variety of non
      canonical effects of telomerase that are independent of telomere lengthening have
      been discovered, and even the notion that telomerase is restricted to very few
      cell types has been questioned. These effects also seem to be important in
      carcinogenesis and might explain the tumor-promoting effects of telomerase
      independently of telomere elongation. Here, the current understanding of the
      extratelomeric roles of telomerase and their physiological and pathological
      significance is reviewed.

PMID- 18623072
TI  - A redesigned genetic code for selective labeling in protein NMR.
AB  - The outline of a universal cell-free translation system capable of site-specific
      insertion of any types of labeled amino acids is presented. The system could be
      an invaluable tool for NMR spectroscopy by making the exclusive and exact
      labeling of the segments of interest possible. Although the development of such a
      system requires considerable efforts and can not be expected to be available in
      the next few years, we argue that recent findings concerning the translation
      apparatus provide clues for overcoming the major difficulties that might arise.
      We propose a genetic code and a reactor expected to fulfill the specific
      requirements. Importantly, incomplete systems could also be useful to study
      selected functional aspects of a number of proteins, examples of which are also
      given.

PMID- 18623071
TI  - What goes on behind closed doors: physiological versus pharmacological steroid
      hormone actions.
AB  - Steroid-hormone-activated receptor proteins are among the best-understood class
      of factors for altering gene transcription in cells. Steroid receptors are of
      major importance in maintaining normal human physiology by responding to
      circulating concentrations of steroid in the nM range. Nonetheless, most studies
      of steroid receptor action have been conducted using the supra-physiological
      conditions of saturating concentrations (> or =100 nM) of potent synthetic
      steroid agonists. Here we summarize the recent developments arising from
      experiments using two clinically relevant conditions: subsaturating
      concentrations of agonist (to mimic the circulating concentrations in mammals)
      and saturating concentrations of antagonists (which are employed in endocrine
      therapies to block the actions of endogenous steroids). These studies have
      revealed new facets of steroid hormone action that could not be uncovered by
      conventional experiments with saturating concentrations of agonist steroids, such
      as a plethora of factors/conditions for the differential control of gene
      expression by physiological levels of steroid, a rational approach for examining
      the gene-specific variations in partial agonist activity of antisteroids, and a
      dissociation of steroid potency and efficacy that implies the existence of
      separate, and possibly novel, mechanistic steps and cofactors.

PMID- 18623073
TI  - Binase and other microbial RNases as potential anticancer agents.
AB  - Some RNases possess preferential cytotoxicity against malignant cells. The best
      known of these RNases, onconase, was isolated from frog oocytes and is in
      clinical trials as anticancer therapy. Here we propose an alternative platform
      for anticancer therapy based on T1 RNases of microbial origin, in particular
      binase from Bacillus intermedius and RNase Sa from Streptomyces aureofaciens. We
      discuss their advantages and the most promising directions of research for their
      potential clinical applications.

PMID- 18623074
TI  - Helicity in electron microscopy images-a comment on Wang TF, Chen LT and Wang AH
      2008 BioEssays 30:48-56.

PMID- 18623075
TI  - Ecogeographic variation in human nasal passages.
AB  - Theoretically, individuals whose ancestors evolved in cold and/or dry climates
      should have greater nasal mucosal surface area relative to air volume of the
      nasal passages than individuals whose ancestors evolved in warm, humid climates.
      A high surface-area-to-volume (SA/V) ratio allows relatively more air to come in
      contact with the mucosa and facilitates more efficient heat and moisture exchange
      during inspiration and expiration, which would be adaptive in a cold, dry
      environment. Conversely, a low SA/V ratio is not as efficient at recapturing heat
      and moisture during expiration and allows for better heat dissipation, which
      would be adaptive in a warm, humid environment. To test this hypothesis, cross
      sectional measurements of the nasal passages that reflect surface area and volume
      were collected from a sample of CT scans of patients of European and African
      ancestry. Results indicate that individuals of European descent do have higher
      SA/V ratios than individuals of African descent, but only when decongested.
      Otherwise, the two groups show little difference. This pattern of variation may
      be due to selection for different SA/V configurations during times of physical
      exertion, which has been shown to elicit decongestion. Relationships between
      linear measurements of the skeletal nasal aperture and cavity and cross-sectional
      dimensions were also examined. Contrary to predictions, the nasal index, the
      ratio of nasal breadth to nasal height, is not strongly correlated with internal
      dimensions. However, differences between the nasal indices of the two groups are
      highly significant. These results may be indicative of different adaptive
      solutions to the same problem.

PMID- 18623076
TI  - Validation of microarray-based resequencing of 93 worldwide mitochondrial
      genomes.
AB  - The human mitochondrial genome consists of a multicopy, circular dsDNA molecule
      of 16,569 base pairs. It encodes for 13 proteins, two ribosomal genes, and 22
      tRNAs that are essential in the generation of cellular ATP by oxidative
      phosphorylation in eukaryotic cells. Germline mutations in mitochondrial DNA
      (mtDNA) are an important cause of maternally inherited diseases, while somatic
      mtDNA mutations may play important roles in aging and cancer. mtDNA polymorphisms
      are also widely used in population and forensic genetics. Therefore, methods that
      allow the rapid, inexpensive and accurate sequencing of mtDNA are of great
      interest. One such method is the Affymetrix GeneChip Human Mitochondrial
      Resequencing Array 2.0 (MitoChip v.2.0) (Santa Clara, CA). A direct comparison of
      93 worldwide mitochondrial genomes sequenced by both the MitoChip and dideoxy
      terminator sequencing revealed an average call rate of 99.48% and an accuracy of
      > or =99.98% for the MitoChip. The good performance was achieved by using in
      house software for the automated analysis of additional probes on the array that
      cover the most common haplotypes in the hypervariable regions (HVR). Failure to
      call a base was associated mostly with the presence of either a run of > or =4 C
      bases or a sequence variant within 12 bases up- or downstream of that base. A
      major drawback of the MitoChip is its inability to detect insertions/deletions
      and its low sensitivity and specificity in the detection of heteroplasmy.
      However, the vast majority of haplogroup defining polymorphism in the mtDNA
      phylogeny could be called unambiguously and more rapidly than with conventional
      sequencing.

PMID- 18623077
TI  - In vitro study on influence of nano particles of CuO on CA1 pyramidal neurons of
      rat hippocampus potassium currents.
AB  - The effects of nano particles of CuO on voltage-dependent potassium currents were
      studied in acutely isolated CA1 pyramidal neurons of rat hippocampus using the
      whole-cell patch-clamp techniques. Nano particles of CuO had small effects on
      transient outward potassium current (I(A), no statistical significance) and
      mainly inhibited delayed rectifier potassium current (I(K)) in the concentration
      of 5 x 10(-5) g/mL. Nano particles of CuO didn't shift the steady-state
      activation curve of I(K) and I(A) but negatively shifted the inactivation curve
      of I(K). The effects on inactivation curve of I(A) had no statistical
      significance. These results suggested that blockades of K+ currents by nano
      particles of CuO could be preferential for I(k) for the first time. This may
      interfere with the normal function of nerve cells.

PMID- 18623078
TI  - Phytotoxic effects of cyanobacteria extract on Lemna minor and Myriophyllum
      spicatum phyto-tolerance and superoxide dismutase activity.
AB  - The research on the effects of microcystins on aquatic plants has increased. Some
      aquatic plants have some tolerance to microcystins but the mechanism of the
      tolerance is still unknown. In this experiment, we used microcystins of different
      concentrations to study the toxic effect in Lemna minor and Myriophyllum
      spicatum. Experiments were carried out with a range of microcysitns levels
      (equivalent to 0, 0.1, 0.5, 1.0, and 4.3 mg/L). The growth of L. minor (as fresh
      weight) and chlorophyll a content were significantly reduced and superoxide
      dismutase (SOD) activity was significantly decreased at microcystins
      concentration up to 0.5 mg/L. The growth of M. spicatum was affected, only
      weakly, by microcystins and 0.5 mg/L and these treatments caused significant
      decrease in chlorophyll a content. Besides, the SOD activity of M. spicatum
      positively correlated to microcystins concentration (P < 0.01). The result
      indicated that M. spicatum was more tolerant to microcystins than L. minor and
      the induced SOD activity may contribute to the tolerance. The experiment also
      indicated that catalase (CAT) activity was not significantly influenced by
      microcystin for both the two tested aquatic plants.

PMID- 18623079
TI  - Effect of soybean on breast cancer according to receptor status: a case-control
      study in Japan.
AB  - The possible association of high soy food consumption with low incidence of
      breast cancer in Asian countries has been widely investigated, but findings from
      epidemiologic studies have been inconsistent. Breast cancers defined by receptor
      status, estrogen receptor (ER), progesterone receptor (PR) and human epidermal
      growth factor receptor 2 (HER2) may have distinct etiologic factors. Here, we
      conducted a case-control study to clarify associations between intake of soybean
      products and breast cancer risk according to receptor status. A total of 678
      breast cancer cases and 3,390 age- and menopausal status-matched noncancer
      controls were included. Odds ratios (ORs) with 95% confidence intervals (CIs)
      were estimated using conditional logistic models adjusted for potential
      confounders. On analysis according to receptor status, we observed a
      significantly reduced risk of ER-positive (ER+) (top tertile OR = 0.74; 95% CI,
      0.58-0.94; trend p = 0.01) and HER2-negative (HER2-) tumors (top tertile OR =
      0.78; 95% CI, 0.61-0.99; trend p = 0.04). Further, when the 3 receptors were
      jointly examined, a reduced risk was observed only in patients with ER+/PR+/HER2-
      tumor (top tertile OR = 0.73; 95% CI, 0.54-0.97; trend p = 0.03). These findings
      indicate that the protective effect of soy against breast cancer risk differs by
      receptor status.

PMID- 18623080
TI  - Pesticide exposure as risk factor for non-Hodgkin lymphoma including
      histopathological subgroup analysis.
AB  - We report a population based case-control study of exposure to pesticides as risk
      factor for non-Hodgkin lymphoma (NHL). Male and female subjects aged 18-74 years
      living in Sweden were included during December 1, 1999, to April 30, 2002.
      Controls were selected from the national population registry. Exposure to
      different agents was assessed by questionnaire. In total 910 (91 %) cases and
      1016 (92%) controls participated. Exposure to herbicides gave odds ratio (OR)
      1.72, 95% confidence interval (CI) 1.18-2.51. Regarding phenoxyacetic acids
      highest risk was calculated for MCPA; OR 2.81, 95% CI 1.27-6.22, all these cases
      had a latency period >10 years. Exposure to glyphosate gave OR 2.02, 95% CI 1.10
      3.71 and with >10 years latency period OR 2.26, 95% CI 1.16-4.40. Insecticides
      overall gave OR 1.28, 95% CI 0.96-1.72 and impregnating agents OR 1.57, 95% CI
      1.07-2.30. Results are also presented for different entities of NHL. In
      conclusion our study confirmed an association between exposure to phenoxyacetic
      acids and NHL and the association with glyphosate was considerably strengthened.

PMID- 18623081
TI  - Does increased urination frequency protect against bladder cancer?
AB  - Experimental studies suggest that increased urination frequency may reduce
      bladder cancer risk if carcinogens are present in the urine. Only 2 small studies
      of the effect of increased urination frequency on bladder cancer risk in humans
      have been conducted with conflicting results. Our purpose was to evaluate the
      effect of urination frequency on risk of bladder cancer in a large, multicenter
      case-control study. We analyzed data based on interviews conducted with 884
      patients with newly diagnosed, bladder cancer and 996 controls from 1998 to 2001
      in Spain. We observed a consistent, inverse trend in risk with increasing
      nighttime voiding frequency in both men (p = 0.0003) and women (p = 0.07);
      voiding at least 2 times per night was associated with a significant, 40-50% risk
      reduction. The protective effect of nocturia was apparent among study
      participants with low, moderate and high water consumption. The risk associated
      with cigarette smoking was reduced by nocturia. Compared with nonsmokers who did
      not urinate at night, current smokers who did not urinate at night had an OR of
      7.0 (95% CI = 4.7-10.2), whereas those who voided at least twice per night had an
      OR of 3.3 (95% CI = 1.9-5.8) (p value for trend = 0.0005). Our findings suggest a
      strong protective effect of nocturia on bladder cancer risk, providing evidence
      in humans that bladder cancer risk is related to the contact time of the
      urothelium with carcinogens in urine. Increased urination frequency, coupled with
      possible dilution of the urine from increased water intake, may diminish the
      effect of urinary carcinogens on bladder cancer risk.

PMID- 18623082
TI  - Water intake and bladder cancer risk in Los Angeles County.
AB  - The overall evidence of an association between fluid intake and bladder cancer is
      not entirely consistent. We examined the fluid intake-bladder cancer relationship
      in the Los Angeles bladder cancer case-control study. A total of 1,586 cases and
      their age-, sex-, and race-matched neighborhood controls were interviewed in
      person from 1987 to 1999. Information on total fluid intake was derived from the
      consumption of specific fluids including water, coffee, tea, alcohol, milk,
      juice, hot chocolate and soda. Total fluid intake was not associated with bladder
      cancer. Daily water intake was associated with a slight decrease in bladder
      cancer risk, with the protection more pronounced among women (p for trend =
      0.039) than among men (p for trend = 0.62). Compared to drinking <1 glass of
      water per day, drinking > or =6 glasses/day was associated with 0.91 (95%
      confidence interval, 0.67-1.22) times the risk of bladder cancer among all
      subjects, 0.94 (0.67-1.32) times the risk among men, and 0.69 (0.36-1.33) times
      the risk among women. The water intake-bladder cancer association also seemed to
      be modified by daytime urination frequency with significant inverse association
      among subjects who urinated > or =6 times/day (p for trend = 0.015), but not
      among those who urinated less frequently. Similarly, the protection from water
      intake was confined to women who did not experience nocturia and to men who did.
      Results from our study suggest that water intake may be associated with a slight
      reduction in bladder cancer risk.

PMID- 18623083
TI  - The enhancer of zeste homolog 2 gene contributes to cell proliferation and
      apoptosis resistance in renal cell carcinoma cells.
AB  - The enhancer of zeste homolog 2 (EZH2) gene has been recently linked to human
      malignancies where it may serve as a new target for cancer therapy. Here, we
      analyzed EZH2 expression in primary renal cell carcinoma (RCC) specimens and in
      nontumorous tissue samples from adult kidney. EZH2 transcripts were detectable in
      all RCC specimens examined. Expression levels were significantly higher in tumor
      tissue (p < or = 0.0001) than in samples from normal adult kidney. Moreover,
      inhibition of endogenous EZH2 expression in RCC cell lines by RNA interference
      (RNAi) led to reduced proliferation and increased apoptosis in RCC cells. These
      data show that EZH2 is overexpressed in RCC. Furthermore, they indicate that the
      EZH2 gene plays a role for both the proliferation and the apoptosis resistance of
      RCC cells. Targeted inhibition of EZH2 could therefore represent a novel strategy
      to improve the therapeutic response of RCC.

PMID- 18623084
TI  - Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic
      review of the evidence from randomized controlled trials.
AB  - Much debate has focused on whether antioxidants interfere with the efficacy of
      cancer chemotherapy. The objective of this study is to systematically review the
      randomized, controlled clinical trial evidence evaluating the effects of
      concurrent use of antioxidants with chemotherapy on toxic side effects. We
      performed a search of literature from 1966-October 2007 using MEDLINE, Cochrane,
      CinAhl, AMED, AltHealthWatch and EMBASE databases. Randomized, controlled
      clinical trials reporting antioxidant-based mitigation of chemotherapy toxicity
      were included in the final tally. Searches were performed following a
      standardized protocol for systematic reviews. Only 33 of 965 articles considered,
      including 2,446 subjects, met the inclusion criteria. Antioxidants evaluated
      were: glutathione (11), melatonin (7), vitamin A (1), an antioxidant mixture (2),
      N-acetylcysteine (2), vitamin E (5), selenium (2), L-carnitine (1), Co-Q10 (1)
      and ellagic acid (1). The majority (24) of the 33 studies included reported
      evidence of decreased toxicities from the concurrent use of antioxidants with
      chemotherapy. Nine studies reported no difference in toxicities between the 2
      groups. Only 1 study (vitamin A) reported a significant increase in toxicity in
      the antioxidant group. Five studies reported the antioxidant group completed more
      full doses of chemotherapy or had less-dose reduction than control groups.
      Statistical power and poor study quality were concerns with some studies. This
      review provides the first systematically reviewed evidence that antioxidant
      supplementation during chemotherapy holds potential for reducing dose-limiting
      toxicities. However, well-designed studies evaluating larger populations of
      patients given specific antioxidants defined by dose and schedule relative to
      chemotherapy are warranted.

PMID- 18623085
TI  - Bidi smoking and lung cancer incidence among males in Karunagappally cohort in
      Kerala, India.
AB  - The association of lung cancer incidence with bidi smoking was examined using a
      cohort study data in Karunagappally, Kerala, India. We sought interview of all
      the residents in Karunagappally with the population of 385,103 in 1991 census,
      and established a cohort of 359,619 (93% of the population in 1991) in the 1990s.
      There were 65,829 men aged 30-84 at interview after excluding those diagnosed as
      cancer or died of any cause before 1997. Among them, 212 newly diagnosed lung
      cancer cases were ascertained during the 8-year period between 1997 and 2004
      through Karunagappally Cancer Registry. The relative risk (RR) of lung cancer was
      obtained from Poisson regression analysis of grouped data. Lung cancer incidence
      was relatively high among Moslem people and those with lower educational history.
      When taking into account attained age, religion and education, the RR between
      current bidi smokers and those who had never smoked bidis was 3.9 (95%CI = 2.6
      6.0, p < 0.001). The lung cancer risk did not return to the level of non-smokers
      within 10 years after cessation. In further analyses using only those never
      smoked cigarettes to examine the effect of bidi smoking alone on lung cancer
      risk, current smokers of bidis had the RR of 4.6 (95%CI = 2.5-8.5, p < 0.001).
      Lung cancer incidence increased with larger amounts of bidi smoked a day (p <
      0.001), with longer durations of smoking bidis (p < 0.001), and with younger ages
      starting smoking bidis (p < 0.001). Immediate measures should be taken to stop
      bidi smoking, which is common in south Asia.

PMID- 18623086
TI  - Caspase-3 enhances lung metastasis and cell migration in a protease-independent
      mechanism through the ERK pathway.
AB  - Caspase-3 is known as a cysteine protease that primarily executes the cell death
      program. However, some tumors express higher levels of caspase-3 in positive
      correlation with malignancy. Here, we showed that caspase-3 can promote tumor
      metastasis in a protease-independent mechanism. Ectopic expression of caspase-3
      enhanced lung metastasis and cell motility of caspase-3 deficient MCF-7 cells. By
      contrast, caspase-3 siRNA reduced the invasiveness and metastasis ability of A549
      cells that express high level of caspase-3. Moreover, caspase-3 induced ERK
      activation. Alteration of caspase-3 by introducing non-processable mutation at
      its cleavage site or treatment of caspase-3 inhibitor did not diminish the
      caspase-3-associated increases in ERK phosphorylation and cell migration.
      Confocal microscopy study showed that caspase-3 was not physically associated
      with ERK. Inhibiting ceramide formation by blockage of the ceramide synthase or
      acid sphingomyelinase activity resulted in significant reduction of ERK
      phosphorylation and cell migration. In summary, caspase-3 induces ERK activation
      through a ceramide-dependant, protease activity-independent mechanism, which
      represents a novel role of caspase-3 in tumor metastasis.

PMID- 18623087
TI  - The Ikaros splice isoform, Ikaros 6, immortalizes murine haematopoietic
      progenitor cells.
AB  - Alternative pre-mRNA splicing is emerging as a major control point in both the
      initiation and progression of tumourigenesis. Overexpression of the dominant
      negative Ikaros splice isoform, Ik6, is found in many human cancers particularly
      leukaemias. Ik6 has been demonstrated to have a role in cell survival in both
      myeloid- and lymphoid cytokine-dependent cell lines. To investigate the oncogenic
      potential of Ik6, we retrovirally transduced murine haematopoietic progenitor
      cells with Ik6 and have analysed the effects on proliferation and differentiation
      of these precursors using myeloid and lymphoid in vitro colony formation assays.
      We found that Ik6 can immortalize haematopoietic progenitor cells in myeloid
      conditions. Using an in vivo transplantation assay, we found that Ik6 favours
      reconstitution by haematopoietic precursors. These findings suggest that Ik6 may
      play an important role in the generation of the leukaemic phenotype.

PMID- 18623088
TI  - IGF1 is a modifier of disease risk in hereditary non-polyposis colorectal cancer.
AB  - Patients diagnosed with HNPCC harbouring a confirmed germline mutation in DNA
      mismatch repair (MMR) genes have an 80% lifetime risk of developing an epithelial
      malignancy. There is, however, considerable variation in the age of disease onset
      in these patients. Insulin-like growth factor-I (IGFI) has been implicated in
      colorectal cancer (CRC), and elevated plasma IGFI levels are associated with both
      sporadic and hereditary CRC risk. In this study, we further investigate the
      cytosine-adenine (CA) dinucleotide repeat polymorphism located near the promoter
      region of IGF1 and its relation to early onset CRC risk in 443 Australian and
      Polish MMR gene mutation carriers using DNA sequencing, Kaplan-Meier survival
      curves and Cox proportional hazard regression analysis. A significantly smaller
      number of IGF1 CA repeats was observed in the Polish patient population, which
      was associated with an earlier age of disease onset compared to the Australian
      patients. The threshold for the observed modifying effect was again shown to be
      in patients with 17 or less CA repeats compared to those with 18 or more.
      Furthermore, when MMR mutation group (i.e., MLH1 or MSH2), gender and family
      clustering were included in the final Cox model we observed a more robust trend
      for the role of the IGF1 CA repeat in predicting age of disease onset in HNPCC
      patients. In addition, this effect was shown to be equal in both MLH1 and MSH2
      mutation carrier groups and not restricted to a particular MMR subgroup (p =
      0.001). We conclude that the IGF1 CA repeat is an important modifier of disease
      onset in HNPCC and the first polymorphism to yield consistent results across
      different populations.

PMID- 18623090
TI  - Influence of cell- and media-derived factors on the integrity of a human
      monoclonal antibody after secretion into serum-free cell culture supernatants.
AB  - To investigate the effects of factors secreted by different cell lines on human
      monoclonal antibody (MAb) integrity, 600 mg of a human MAb, which specifically
      binds to human erythrocytes, were produced in a perfusion process. After
      purification by protein A affinity chromatography, the MAb was used for integrity
      testing in supernatants of several cell lines to investigate their potential to
      degrade the antibody in the extracellular environment. One insect cell line (IPLB
      SF-21 AE) and four mammalian cell lines [CHO K1, BHK-21 (C13), C1271, P3-X63
      Ag8.653], all of them commonly used for the production of recombinant proteins,
      and the human-human-mouse heterohybridoma cell line itself (H-CB-hahE), were
      adapted to serum-free culture media. For integrity testing all cell lines were
      cultivated in spinner flasks using serum-free media supplemented with 30 mug mL(
      1) of purified MAb. MAb integrity was assayed by SDS polyacrylamide gel
      electrophoresis (SDS-PAGE), isoelectric focusing, both followed by Western
      blotting, and an antigen binding assay. None of the mammalian cells showed any
      detectable effects on antibody stability and integrity during exponential growth,
      whereas isoelectric focusing of monoclonal antibody taken from IPLB-SF-21 AE
      culture supernatants revealed a new band indicating a partial modification of the
      MAb by secreted factors of these cells. This observation did not correlate with
      the total proteolytic activity, which was measured in all supernatants and found
      to be lowest in the insest cell cultures. For mammalian cell cultures, it could
      be concluded from these findings that shifts of the antibody microheterogeneity
      pattern, which can be found normally as a result of variations in different
      production parameters, are not caused by extracellular factors once the product
      has been secreted into the supernatant. In addition to their well-known
      advantages in posttranslational modifications (e.g., formation of complex type N
      glycans), mammalian cells appear to be more suitable as expression systems for
      human monoclonal antibodies to be used in vivo when compared with baculovirus
      infected insect cells. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623091
TI  - Membrane bioreactor with a porous hydrophobic membrane as a gas-liquid contactor
      for waste gas treatment.
AB  - A novel type of bioreactor for waste gas treatment has been designed. The reactor
      contains a microporous hydrophobic membrane to create a large interface between
      the waste gas and the aqueous phase. To test the new reactor, propene was chosen
      because of its high air/water partition coefficient, which causes a low water
      concentration and hampers its removal from air. Propene transfer from air to a
      suspension of propene-utilizing Xanthobacter Py2 cells in the membrane bioreactor
      proved to be controlled by mass transfer in the liquid phase. The resistance of
      the membrane was negligible. Simulated propene transfer rates agreed well with
      the experimental data. A stable biofilm of Xanthobacter Py2 developed on the
      membrane during prolonged operation. The propene flux into the biofilm was 1 x
      10(-6) mol m(-2) s(-1) at a propene concentration of 9.3 x 10(-2) mol m(-3) in
      the gas phase. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623092
TI  - Molecular assembly of proteins and conjugated polymers: Toward development of
      biosensors.
AB  - A molecular assembly in which a conjugated polymer is interfaced with a
      photodynamic protein is described. The conjugated polymer, functionalized with
      biotion, is designed such that it can be physisorbed on or chemically grown off a
      glass surface. The streptavidin-derivatized protein is immobilized on the
      biotinylated polymer matrix through the strong biotin-streptavidin interactions.
      The assembly, built on the surface of an optical fiber or on the inside walls of
      a glass capillary, forms an integral part of a biosensor for the detection of
      environmental pollutants such as organophosphorus-based insecticides. The Protein
      in the system can be replaced by any biological macromolecule of interest. We
      study one specific case, the enzyme alkaline phosphatase. The enzyme catalyzes a
      reaction producing an intermediate compound that chemiluminesces, and the
      chemiluminescence singnal is monitored to detect and quantify insecticides such
      as paraoxon and methyl parathion. Preliminary results indicate ppb level
      detection with response time less than 1 minute. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623093
TI  - On-line calibration of a computerized biosensor system for continuous
      measurements of glucose and lactate.
AB  - An on-line calibration procedure for application in continuous monitoring systems
      has been developed. Control of the calibration value and recalibration on-line
      during monitoring is possible without having to disrupt the sample withdrawal.
      The calibration procedure has been applied and evaluated in a continuous
      biosensor system based on the detection of oxygen depletion during enzymatic
      substrate conversion by immobilized oxidases. Evaluation included on-line
      calibration during continuous measurements of glucose and lactate in bovine blood
      samples. Calibration of the complete system consisting of a sampling device, a
      sample handling step, a biocatalytic step, a detection step, and a data
      processing unit is performed by the on-line addition of a calibration solution to
      a blank sample which is fed through the system. The calibration cycle is
      completed within 5.5 min. When recalibration is carried out during monitoring,
      the calibration solution is added to the sample, instead of to a blank sample,
      and the increase in outlet singl is registered. The major advantage of this
      internal standard principle is that the calibration solution is fed through the
      whole system according to the same path as the sample solution and thus takes
      into account all parameters influencing the sample. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623094
TI  - Influence of water activity on the synthesis of triolein catalyzed by immobilized
      Mucor miehei lipase.
AB  - The influence of the thermodynamic activity of water (a(w))on the synthesis of
      triolein catalyzed by Mucor miehei lipase was investigated. Its effect on the
      equilibrium and on the rates of the different reactions present, esteification
      and mono- and diglyceride isomerization, was evaluated through measurements made
      in controlled water activity atmosphere. The apparent equilibrium constants were
      measured from the concentration of the different species as a function of the
      intial glycerol-to oleic-acid ratio using all the values at once with a multi
      response nonlinear regression technique. Rate constants were determined from
      kinetic measurements and non-linear regression uning the variation of the
      concentration of all significant species in the system. Except for the synthesis
      of diolein from monoolein, which shows a maximum for a(w) approximately 0.5, the
      apparent rate constants of the various reactions are not significantly affected
      by the value of the water activity. The equilibrium is shifted to-ward the
      synthesis of triolein for low values of a(w), indicating that in the design of a
      process for triglyceride synthesis, using M. miehei lipase as a catalyst, the
      water activity can be lowered to extreme values to favor the synthesis, without
      any sacrifice on the productivity of the process. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623095
TI  - Real-time fuzzy-knowledge-based control of Baker's yeast production.
AB  - A real-time fuzzy-knowledge-based system for fault diagnosis and control of
      bioprocesses was constructed using the object-oriented programming environment
      Small-talk/V Mac. The basic system was implemented in a Macintosh Quadra 900
      computer and built to function connected on line to the process computer. Fuzzy
      logic was employed in handling uncertainties both in the knowledge and in
      measurements. The fuzzy sets defined for the process variables could be changed
      on-line according to process dynamics. Process knowledge was implemented in a
      graphical two-level hierachical knowledge base. In on-line process control the
      system first recognizes the current process phase on the basis of top-level rules
      in the knowledge-base. Then, according to the results of process diagnosis based
      on measurement data, the appropriate control strategy is subsequently inferred
      making use of the lower level rules describing the process during the phase in
      question. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623096
TI  - Serum-free cell culture on insulin-immobilized porous collagen beads.
AB  - Insulin or albumin was immobilized on collagen beads using water-soluble
      carbodiimide. Adhesion of STO mouse fibroblast cells onto the beads decreased
      with increasing the amount of immobilized proteins. Growth of the cells was
      remarkably accelerated on the insulinimmobilized collagen beads, which can be
      used for serum-free cell culture. The growth acceleration became larger with
      increasing the amount of immobilized insulin, while it became smaller with
      increasing the amount of immobilized albumin. In addition, the immobilized
      insulin more strongly accelerated the cell growth than free insulin plus collagen
      beads. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623097
TI  - Buffer exchange using size exclusion chromatography, countercurrent dialysis, and
      tangential flow filtration: Models, development, and industrial application.
AB  - There are three major methods for buffer exchange of proteins at industrial
      scale: size exclusion chromatography (SEC), tangential flow filtration (TFF), and
      countercurrent dialysis (CCD). In order to determine the optimal technology for a
      given process, a study was done to compare these technologies on a technological
      and economic basis. This comparison required that new mathematical models be
      developed which enable the common features of each unit operation to be directly
      compared. The new concept of a diavolume equivalent for SEC, defined as the
      inverse of the fractional loading, was also introduced to aid in this comparison.
      Variables that were examined for each unit operation included range of buffer
      exchange, dilution of protein solution, yield, buffer requirements, total
      operating time, throughput, plant space, capital, raw materials, and labor costs.
      It was found that TFF and CCD have a greater range of buffer exchange than SEC.
      TFF also provides the advantage that concentration of the protein can readily be
      accomplished in the same step. For processes of equal batch size and yield, TFF
      and CCD also provide a two- to five- fold improvement in each of the remaining
      variables. The major economic advantage in using TFF and CCD over SEC is the
      decreased plant size required for manufacturing and thus the longer term use of
      existing facilities. Situations where SEC (or CCD) would be favored over TFF are
      when protein denaturation occurs in TFF but does not occur in SEC. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623098
TI  - A mathematical model for the leukocyte filtration process.
AB  - Leukocyte filters are applied clinically to remove leukocytes from blood. In
      order to optimize leukocyte filters, a mathematical model to describe the
      leukocyte filtration process was developed by modification of a general
      theoretical model for depth filtration. The model presented here can be used to
      predict the time-dependent leukocyte filtration as a function of cell-cell
      interaction in the filter, filter efficiency, filter capacity, filter dimensions,
      and leukocyte concentration in the suspension applied to the filter. The results
      of different leukocyte filtration experiments previously reported in the
      literature could be well described by the present model. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623099
TI  - A study of mass transfer in yeast in a pulsed baffled bioreactor.
AB  - We report experimental data of mass transfer of oxygen into yeast resuspension in
      a pulsed baffled bioreactor. The bioreactor consists of a 50-mm-diameter column
      with the presence of a series of either wall (orifice) or central (disc) baffles
      or a mixture of both where fluid oscillation can also be supermposed during the
      experiments. Air bubbles are sparged into the bottom of the pulsed baffled
      bioreactor, and the kinetics of liquid oxygen concentration in the yeast solution
      is followed using a dissolved oxygen probe with a fast response time of 3 s
      together with the dynamic gassing-out technique. Among the three different baffle
      geometries investigated, the orifice baffles gave the highest and sharpest
      increase in the oxygen transfer rate, and the trends in the k(L)a measurements
      are consistent with the fluid mechanics observed within both the systems and
      previous work. In addition, we have also compared the k(L)a values with those
      obtained in a stirred tank; an 11% increase in the K(L)a is reported. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623100
TI  - Cultivation of hybridoma cells in an inclined bioreactor.
AB  - Murine hybridoma cells were grown in a bubble column that was inclined up to 45
      degrees from vertical. Inclining the column by a few degrees separated the rising
      bubbles against the upper surface, leaving the bulk of the liquid bubble free.
      The liquid was circulated well by the rising bubbles, but collection of cells by
      rising bubbles and exposure of cells to bursting bubbles were minimized. Maximum
      viable cell count and exponential growth of the cells were not affected by
      inclination, but an inclination of 30 degrees gave an antibody titer of 42 mg/L,
      which more than doubled the yield of 17 mg/L in the vertical position. By
      comparison, the culture gave yields of 30 mg/L when grown in spinner flasks. The
      enhanced antibody production in the inclined bioreactor corresponded to a
      prolonged stationary phase of 45 h. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623101
TI  - Ab-initio simulations of materials using VASP: Density-functional theory and
      beyond.
AB  - During the past decade, computer simulations based on a quantum-mechanical
      description of the interactions between electrons and between electrons and
      atomic nuclei have developed an increasingly important impact on solid-state
      physics and chemistry and on materials science-promoting not only a deeper
      understanding, but also the possibility to contribute significantly to materials
      design for future technologies. This development is based on two important
      columns: (i) The improved description of electronic many-body effects within
      density-functional theory (DFT) and the upcoming post-DFT methods. (ii) The
      implementation of the new functionals and many-body techniques within highly
      efficient, stable, and versatile computer codes, which allow to exploit the
      potential of modern computer architectures. In this review, I discuss the
      implementation of various DFT functionals [local-density approximation (LDA),
      generalized gradient approximation (GGA), meta-GGA, hybrid functional mixing DFT,
      and exact (Hartree-Fock) exchange] and post-DFT approaches [DFT + U for strong
      electronic correlations in narrow bands, many-body perturbation theory (GW) for
      quasiparticle spectra, dynamical correlation effects via the adiabatic-connection
      fluctuation-dissipation theorem (AC-FDT)] in the Vienna ab initio simulation
      package VASP. VASP is a plane-wave all-electron code using the projector
      augmented wave method to describe the electron-core interaction. The code uses
      fast iterative techniques for the diagonalization of the DFT Hamiltonian and
      allows to perform total-energy calculations and structural optimizations for
      systems with thousands of atoms and ab initio molecular dynamics simulations for
      ensembles with a few hundred atoms extending over several tens of ps.
      Applications in many different areas (structure and phase stability, mechanical
      and dynamical properties, liquids, glasses and quasicrystals, magnetism and
      magnetic nanostructures, semiconductors and insulators, surfaces, interfaces and
      thin films, chemical reactions, and catalysis) are reviewed.

PMID- 18623102
TI  - Validation of fecal elastase-1 determination using immunoenzymatic assay in HIV
      infected patients.
AB  - Pancreatic elastase-1 is a proteolytic enzyme exclusively produced in the
      pancreas, is stable when passing through the bowel, and its determination is
      associated with chronic pancreatitis. The clinical diagnosis of pancreatitis is
      based on anamnesis, physical examination, radiological, sonographic, endoscopic,
      and laboratory findings. Nowadays, there is a test for the determination of fecal
      elastase-1, by enzymatic reaction (enzyme-linked immunosorbent assay, ELISA),
      which specifically determines human elastase-1, promoting the pancreatic function
      evaluation. Parameters such as linearity, calibration curve, sensitivity,
      specificity, precision, accuracy, recovery, and receiver operator characteristic
      (ROC) curve are used to evaluate the test. The aim of this study was the
      validation of the immunoenzymatic assay (ELISA) and the use of its results in
      patients with HIV, alcoholics, and under antiretroviral therapy. The study
      involved 157 patients, 95 of them were HIV-infected, and 62 were completely
      healthy. The elastase-1 ELISA kit from Bioserv was used, and we noted that the
      obtained results were linear, sensitive, precise, and accurate. Moreover, our
      results suggest that this test can be a laboratory evaluation to determine the
      relationship of pancreatitis with alcohol use, but not its association with
      antiretroviral use in HIV patients (P=0.424). This test is useful to diagnose
      pathologies related to pancreatic insufficiency.

PMID- 18623103
TI  - Estimation of vitamin B1 excretion in 24-hr urine by assay of first-morning
      urine.
AB  - Urinary B1 (vitamin B1) excretion is commonly determined in 24-hr urine specimens
      to obtain an estimate of nutritional status. The aim of our study was to
      investigate whether B1 in random urine specimens, corrected for the urine
      creatinine (Cr), can be substituted for B1 in 24-hr urines. Collection of such
      hour urines is often fraught with errors; an alternative method is described
      here. All urine specimens voided over 24 hr were collected from 32 healthy adults
      as were the first-morning urines from 30 healthy Japanese women. The B1 excretion
      was expressed as the ratio of B1 to Cr. Although the B1 excretion was expressed
      as the B1/Cr ratio, the B1 excretion varied with the urine volume and the time of
      urine collection. The B1/Cr ratio in random urine specimens not collected at a
      fixed time may mislead the evaluation of the nutritional status. We found that
      the B1/Cr ratio in the first-morning urine correlated significantly with the
      ratio in 24-hr urines (r=0.970, P<0.001) and also with the concentration of total
      B1 (B1 plus its phosphate esters) in whole blood (r=0.733, P<0.001). We conclude
      that the B1/Cr ratio in 24-hr urines could be estimated by measuring the ratio in
      the first-morning urine.

PMID- 18623104
TI  - Prognostic potential of a PSA complex in sera of prostate cancer patients with
      alpha2-macroglobulin deficiency.
AB  - We previously reported on a number of cases of metastatic prostate cancer (PCa)
      in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to
      less than 20 mg/dl (alpha2M deficiency). In order to elucidate the relative
      proportions of free and a prostate-specific antigen (PSA) complex in PCa patients
      with alpha2M deficiency, we have assessed serum alpha2M and total PSA levels, and
      ratios of free PSA to total PSA (F/T ratios) at each stage of PCa. Moreover, the
      PSA reactivity profile was determined on fractionated serum specimens of PCa
      patients using high-performance liquid chromatography (HPLC) using a TSKG-3000
      SWXL column. Measurement of alpha2M concentration was performed by laser
      nephelometry. PSA levels were determined by enzyme immunoassay, free PSA by
      radioimmunoassay. In those PCa patients with alpha2M deficiency, serum alpha2M
      and F/T ratios were lower, whereas PSA levels were higher when compared with
      those PCa patients without alpha2M deficiency (P<0.05). PSA elution profiles on
      HPLC columns revealed two major peaks. The proportion of PSA-antichymotrypsin
      (PSA-ACT) increased, whereas the proportion of free PSA decreased in PCa patients
      with alpha2M deficiency as compared with those PCa patients without alpha2M
      deficiency. F/T ratios were significantly lower in PCa patients with alpha2M
      deficiency than in those PCa patients without alpha2M deficiency. PSA-ACT and F/T
      ratio may be useful for monitoring bone metastasis in PCa.

PMID- 18623105
TI  - Analysis of simulated scanning of atomic-scale silicon surface by atomic force
      microscopy.
AB  - This study constructs a contact-mode atomic force microscopy (AFM) simulation
      measurement model with constant force mode to simulate and analyze the outline
      scanning measurement by AFM. The simulation method is that when the probe passes
      the surface of sample, the action force of the atom of sample received by the
      atom of the probe can be calculated by using Morse potential. Through
      calculation, the equivalent force on the cantilever of probe can be acquired. By
      using the deflection angle equation for the cantilever of probe developed and
      inferred by this study, the deflection angle of receiving action force can be
      calculated. On the measurement point, as the deflection angle reaches a fixed
      deflection angle, the scan height of this simulation model can be acquired. By
      scanning in the right order, the scan curve of the simulation model can be
      obtained. By using this simulation measurement model, this study simulates and
      analyzes the scanning of atomic-scale surface outline. Meanwhile, focusing on the
      tip radii of different probes, the concept of sensitivity analysis is employed to
      investigate the effects of the tip radius of probe on the atomic-scale surface
      outline. As a result, it is found from the simulation on the atomic-scale surface
      that within the simulation scope of this study, when the tip radius of probe is
      greater than 12 nm, the effects of single atom on the scan curve of AFM can be
      better decreased or eliminated.

PMID- 18623106
TI  - The analysis of morphological distortion during AFM study of cells.
AB  - Atomic force microscopy (AFM) has been widely applied in cellular morphology
      study. However, morphological information including volume and roughness obtained
      by AFM are usually affected by different kinds of factors, which include the
      microscopic system itself, imaging mode, or external factors such as AFM probe or
      tip condition. In this study, based on red blood cell model, the dependence of
      cellular morphology, volume, and roughness on several parameters of the imaging
      was evaluated and, furthermore, a general rule and resolution for trustful
      analysis had been suggested. In addition, the potential effects that resulted
      from sample itself had also been analyzed based on adhesive force analysis. The
      results indicated that the scanning range and the imaging mode affect cellular
      volume and roughness, and the distorted images should be ascribed to blunt tip,
      contaminated tip, and the shape of tip. The analysis of morphological distortion
      during AFM investigation of cells provides a reference for researchers using AFM.

PMID- 18623107
TI  - Lung ventilation during treadmill locomotion in a semi-aquatic turtle, Trachemys
      scripta.
AB  - It is reasonable to presume that locomotion should have a mechanical effect on
      breathing in turtles. The turtle shell is rigid, and when the limbs protract and
      retract, air in the lungs should be displaced. This expectation was met in a
      previous study of the green sea turtle, Chelonia mydas; breathing completely
      ceased during terrestrial locomotion (Jackson and Prange, 1979. J Comp Physiol
      134:315-319). In contrast, another study found no direct effect of locomotion on
      ventilation in the terrestrial box turtle, Terrapene carolina (Landberg et al.,
      2003. J Exp Biol 206:3391-3404). In this study we measured lung ventilation
      during treadmill locomotion in a semi-aquatic turtle, the red-eared slider,
      Trachemys scripta. Sliders breathed almost continuously during locomotion and
      during brief pauses between locomotor bouts. Tidal volume was relatively small
      (approximately 1 mL) during locomotion and approximately doubled during pauses.
      Minute ventilation was, however, not significantly smaller during locomotion
      because breath frequency was higher than that during the pauses. We found no
      consistent evidence for phase coupling between breathing and locomotion
      indicating that sliders do not use locomotor movements to drive breathing. We
      also found no evidence for a buccal-pump mechanism. Sliders, like box turtles,
      appear to use abdominal musculature to breathe during locomotion. Thus,
      locomotion affects lung ventilation differently in the three turtle species
      studied to date: the terrestrial Te. carolina shows no measurable effect of
      locomotion on ventilation; the semi-aquatic Tr. scripta breathes with smaller
      tidal volumes during locomotion; and the highly aquatic C. mydas stops breathing
      completely during terrestrial locomotion.

PMID- 18623108
TI  - Lung and metabolic development in mammals: contribution to the reconstruction of
      the marsupial and eutherian morphotype.
AB  - Marsupials represent only 6% of all living mammals. Marsupialia and Placentalia
      are distinguished mainly by their modes of reproduction. In particular, the
      differences in the stage of development of the neonates may be one explanation
      for the divergent evolutionary success. In this respect one important question is
      whether the survivability of the neonate depends on the degree of maturation of
      the respiratory system relative to the metabolic capacity at the time of birth.
      Therefore, this review highlights the differences in lung morphology and
      metabolic development of extant Marsupialia and Placentalia. The Marsupial
      neonate is born with a low birth weight and is highly immature. The neonatal lung
      is characterized by large terminal sacs, a poorly developed bronchial system and
      late formation of alveoli. Marsupialia have a low metabolic rate at birth and
      attain adult metabolic rate and thermoregulatory capacity late in postnatal
      development. In contrast, the eutherian neonate is born with a relative high
      birth weight and is always more mature than marsupial neonates. The neonatal lung
      has small terminal sacs, the bronchial system is well developed and the formation
      of alveoli begins few days after birth. Placentalia have a high metabolic rate at
      birth and attain adult metabolic rate and thermoregulatory capacity early in
      postnatal development. The differences in the developmental degree of the newborn
      lung between Marsupialia and Placentalia have consequences for their metabolic
      and thermoregulatory capacity. These differences could be advantageous for
      Placentalia in the changing environments in which they evolved.

PMID- 18623109
TI  - A modified grading system for post-hepatectomy metastatic liver cancer
      originating from colorectal carcinoma.
AB  - BACKGROUND AND OBJECTIVES: There is no appropriate grading system for prediction
      of survival of patients with metastatic liver cancer (MLC) from colorectal
      carcinoma. We propose the modified grading system for MLC from the present
      Japanese system. METHODS: We compared predictive accuracies of survival of 121
      Japanese MLC patients of five systems, including clinical risk score (CRS)
      proposed by Memorial-Sloan-Kettering-Cancer-Center, original H-number (OHN) by
      Japanese Society for Cancer of the Colon and Rectum, revised H-number (RHN) and
      Grade by the same society (GJSCCR), and our modified Grade (MGJSCCR) based on OHN
      and presence of primary lymph node metastasis. RESULTS: Univariate analysis
      showed that discrimination of both disease-free and overall survival rates was
      significant for CRS, OHN and MGJSCCR (P < 0.05) but not for RHN and GJSCCR.
      Multivariate analysis showed CRS and MGJSCCR as the best systems for predicting
      disease-free and overall survival according to disease stage, for which Akaike
      information criteria (AIC) value was the lowest (423.7 and 313.9, hazard ratio
      1.73 and 1.47, respectively for CRS, 423.9 and 313.5, hazard ratio 1.75 and 1.69,
      respectively for MGJSCCR; P < 0.05). CONCLUSIONS: The simpler system of MGJSCCR
      is a better predictive grading system of prognosis of MLC patients who had
      undergone hepatic resection.

PMID- 18623110
TI  - Aberrant crypt foci as precursors in colorectal cancer progression.
AB  - Colorectal cancer progression originates when accumulated genetic and epigenetic
      alterations cause genomic instability and a malignant phenotype. Subsequent
      molecular pathway deregulation leads to histopathologic changes that are
      clinically evident as aberrant crypt foci (ACF) and visualized by high
      magnification chromoscopic colonoscopy. ACF are biomarkers of increased
      colorectal cancer risk, particularly those with dysplastic features. Genetic
      profiling using genomic instability, loss of heterozygosity, and methylation
      analysis has revealed a minority population of ACF genotypically analogous to
      cancer.

PMID- 18623111
TI  - Endothelin-1 enhances the expression of the androgen receptor via activation of
      the c-myc pathway in prostate cancer cells.
AB  - Increasing evidence suggests that androgen independent prostate cancer (PC)
      maintains a functional androgen receptor (AR) pathway despite the low levels of
      circulating androgen following androgen withdrawal, the molecular mechanisms of
      which are not well defined yet. To address this question, we investigated the
      effects of endothelin-1 (ET-1) on AR expression. Western analysis and RT-PCR
      revealed that in the presence of ET-1, levels of AR significantly increased in a
      time- and dose-dependent manner in LNCaP cells. Pretreatments with inhibitors of
      Src and phosphoinositide kinase 3 (PI-3K) suppressed ET-1-induced AR expression.
      As ET-1 was reported to cause a transient increase in c-myc mRNA levels, we
      examined the involvement of c-myc in ET-1-mediated AR expression. Transient
      transfection of c-myc siRNA neutralized ET-1-induced AR expression, suggesting
      that AR induction by ET-1 is c-myc dependent. AR can regulate the transcription
      of its own gene via a mechanism in which c-myc plays a crucial role. Therefore,
      we assessed if ET-1-induced-c-myc leads to the enhancement of AR transcription.
      Reporter gene assays using the previously identified AR gene enhancer containing
      a c-myc binding site were conducted in LNCaP cells. We found that ET-1 induced
      reporter gene activity from the construct containing the wild-type but not mutant
      c-myc binding site. Chromatin immunoprecipitation assays confirmed that ET-1
      increased interaction between c-myc and c-myc binding sites in AR enhancer,
      suggesting that ET-1-induced AR transcription occurs via c-myc-mediated AR
      transcription. Together, these data support the notion that ET-1, via Src/PI-3K
      signaling, augments c-myc expression leading to enhanced AR expression in PC.

PMID- 18623112
TI  - A simple, rapid, and convenient Luminex-compatible method of tissue isolation.
AB  - Various pathological conditions are associated with changes in multiple protein
      biomarkers, and these changes can be assessed using xMAP beads and the Luminex
      platform. Although this platform is most commonly utilized in the analysis of
      biomarkers in serum, plasma, or urine, it is often desirable to measure these
      analytes in tissues (e.g., biopsy specimens). We have developed a simple, rapid
      method of tissue isolation in which excised tissues are permeabilized in RNAlater
      at 4 degrees C overnight, followed by Luminex analysis for inflammatory
      biomarkers (cytokines). This method was compared with flash-freezing in both
      mouse liver and human debrided wound specimens, and may be of utility in other
      clinical settings.

PMID- 18623113
TI  - Serum N-acetyl-beta-D-glucosaminidase profiles in type 1 diabetes secondary
      complications: causes of changes and significance of determination.
AB  - The connection between changes in the activity of serum N-acetyl-beta-D
      glucosaminidase (NAG, E.C.3.2.1.30) and iso-enzymes and degree of secondary
      complications was analyzed in four groups of type 1 diabetic patients (n=69):
      without complications (n=22); with retinopathy (n=16); with retinopathy and
      polyneuropathy (n=13), and with retinopathy, neuropathy, and nephropathy (n=18).
      In all groups statistically significant higher (P<0.001) percent fraction of A
      form (83.84+/-6.09, 84.37+/-5.74, 81.76+/-6.02, 76.37+/-7.38%, resp.) and lower
      (P<0.001, P<0.01) fraction of B form (15.87+/-5.65, 15.66+/-5.74, 18.33+/-5.98,
      23.63+/-7.38, resp.) in total NAG compared with the control (A=69.38+/-4.79%,
      B=30.61+/-4.78%) were found. The differences in A as well as B forms between
      diabetic groups were not statistically significant. Significant strong positive
      correlations between total NAG and glycemia (0.494-0.623), total NAG and A form
      (0.934-0.966), and A form and glycemia (0.512-0.638) were found in all groups. No
      correlation was found between the fractions of B and A forms, except in the
      fourth group. The A form of diabetic patients in the fourth group was more acidic
      compared with the control and other diabetic groups. It was concluded that the
      changes in serum NAG and iso-enzymic profiles in diabetes are the consequence of
      its increased exocytose, especially of the A form, in hyperglycemia and
      posttranslational modifications of iso-enzymes. The total activity of serum NAG
      and iso-enzymic profiles cannot be used for monitoring the development and
      distinction of type 1 diabetes secondary complications.

PMID- 18623114
TI  - Identification of truncated chemokine receptor 7 in human colorectal cancer
      unable to localize to the cell surface and unreactive to external ligands.
AB  - Chemokine receptors are thought to be involved in the process of cancer
      metastases. When investigating cell lines and tissues from colorectal cancer
      (CRC), the CCR7 protein unexpectedly was confined to the cytoplasm and not
      present on the cell surface. This study investigated at the DNA, mRNA and protein
      level, the mechanism and the consequences of the failure of CCR7 to localize to
      the cell membrane. In all 15 CRC cell lines tested, no surface CCR7 was detected
      and no chemotactic response was elicited upon in-vitro exposure to CCR7 chemokine
      ligands (CCL) 19 and CCL21. Integrity of CCR7 DNA and mRNA was examined with
      respect to signal peptide expression in cell lines and CRC tissues by real-time
      RT-PCR and sequencing. Nine of 15 CRC cell lines and 8 of 14 CRC tissues revealed
      a truncated CCR7 mRNA species containing various incomplete signal peptide
      encoding sequences, while the corresponding DNA was intact. These results
      indicate in CRC frequent alternative splicing or post-transcriptional mRNA
      modification resulting in a CCR7 molecule lacking an intact signal peptide
      prohibiting membrane translocation. Further studies would be necessary to
      identify a potential intracellular role of the truncated CCR7, abundantly present
      in the cytoplasm.

PMID- 18623115
TI  - New cancer susceptibility loci: population and familial risks.
AB  - The recent large genotyping studies have identified a new repertoire of cancer
      susceptibility genes and loci which are characterized by common risk alleles and
      low relative risks. Because of these properties, these loci explain a much larger
      proportion of the etiology of the particular cancers, described by the population
      attributable fraction (PAF), than of their familial risks (FRRs). For breast
      cancer, the 9 established loci gave a joint PAF of >60%, but explaining only some
      8% of the empirical FRR. For prostate cancer, 6 independent loci at chromosome 8q
      conferred a joint PAF of 35% but the loci explained no more than 1.9% of the
      empirical excess familial risks. For colorectal cancer, the contributions of the
      2 identified loci to PAF and FRR were somewhat lower. The genome-wide array
      platforms have been built for common variants, constraining the results to
      variants with high PAFs and low FRRs. However, the common variants are likely to
      tag rarer causative variants with much higher FRRs. The detected loci are
      noncoding and the underlying genetic mechanisms have not been worked out. The
      data suggest, in spite of the reservations for combining data on PAFs across
      populations, that the published first-generation genome-wide scans on breast,
      prostate and colorectal cancers have made successful inroads into genomics of
      common cancers, yet leaving the mechanisms to be explained.

PMID- 18623116
TI  - Folate deprivation induces BCRP (ABCG2) expression and mitoxantrone resistance in
      Caco-2 cells.
AB  - Folates can induce the expression and activity of the breast-cancer-resistance
      protein (BCRP) and the multidrug-resistance-protein-1 (MRP1). Our aim was to
      study the time-dependent effect of folate deprivation/supplementation on (i) BCRP
      and MRP expression and (ii) on drug resistance mediated by these transporters.
      Therefore Caco-2 colon cancer cells usually grown in standard RPMI-medium
      containing supraphysiological folic acid (FA) concentrations (2.3 muM; high
      folate, HF) were gradually adapted to more physiological folate concentrations (1
      nM leucovorin (LV) or 1 nM FA; low-folate, LF), resulting in the sublines Caco-2
      LF/LV and Caco-2-LF/FA. Caco-2-LF/LV and LF/FA cells exhibited a maximal increase
      of 5.2- and 9.6-fold for BCRP-mRNA and 3.9- and 5.7-fold for BCRP protein
      expression, respectively, but no major changes on MRP expression. Overexpression
      of BCRP in the LF-cells resulted in 3.6- to 6.3-fold resistance to mitoxantrone
      (MR), which was completely reverted by the BCRP inhibitor Ko143. On the other
      hand, LF-adapted cells were markedly more sensitive to methotrexate than the HF
      counterpart, both after 4-hr (9,870- and 23,923-fold for Caco-2-LF/LV and LF/FA,
      respectively) and 72-hr (11- and 22-fold for Caco-2-LF/LV and LF/FA,
      respectively) exposure. Immunofluorescent staining observed with a confocal-laser
      scan-microscope revealed that in Caco-2 cells (both HF and LF), BCRP is mainly
      located in the cytoplasm. In conclusion, folate deprivation induces BCRP
      expression associated with MR resistance in Caco-2 cells. The intracellular
      localization of BCRP in these cells suggests that this transporter is not
      primarily extruding its substrates out of the cell, but rather to an
      intracellular compartment where folates can be kept as storage.

PMID- 18623117
TI  - Morphometrics of wild black-and-white ruffed lemurs [Varecia variegata; Kerr,
      1792].
AB  - This study presents the first detailed morphometric measurements of wild caught
      black-and-white ruffed lemurs (Varecia variegata) from the eastern rainforests of
      Madagascar and aims to quantify the morphological variation present throughout
      their recognized range. One hundred and forty-four adult and juvenile individuals
      from 15 sites were sampled for 20 cranial, dental and postcranial morphometric
      and body mass measurements. Data were collected from an equal number of male and
      female individuals sampled across seasons over a 7-year period (1999-2002, 2004
      2006). Results indicate that adult body mass and morphometric measurements varied
      between sexes across sites; however, the only significant intersexual difference
      found was that females possessed, on average, longer tails than males. Contrary
      to previous studies, significant seasonal variation could not be detected in
      either male or female body mass or testicular volume (i.e., breeding vs.
      nonbreeding, food-scarce vs. food-abundant seasons). Measurements did, however,
      vary significantly by site and subspecies, though clinal variation could not
      explain these differences. The introduced population from Nosy Mangabe exhibited
      significantly lower body mass and overall body length than all other populations;
      however, this distinction may not have been attributable to natural variation,
      and may have instead resulted from the ecologically restrictive habitat (e.g.,
      unusually high lemur population densities, limited food resources, ecological
      isolation) of this introduced population. Finally, although fore-to-hindlimb,
      brachium-to-thigh and hindlimb indices were comparable to previous values,
      forelimb indices calculated here deviate significantly from previous reports,
      placing V. variegata within the upper range of lemurid taxa. It is currently
      unknown whether this is an artifact of sampling methods (i.e., live vs. skeletal
      specimens) or whether this is an avenue that warrants further investigation.

PMID- 18623118
TI  - Detection of ciguatoxin in fish tissue using sandwich ELISA and neuroblastoma
      cell bioassay.
AB  - The applicability of a new enzyme-linked immunoassay (ELISA) for detecting
      ciguatoxin (CTX) in fish tissue was evaluated by testing three fish species
      commonly implicated in ciguatera fish poisoning in Hawaii. A total of 164
      individual almaco jack (Seriola rivoliana) and greater amberjack (S. dumerili)
      and a total of 175 individuals of the blue-spotted grouper (Cephalopholis argus)
      were caught at various locations in the Hawaiian Islands. Muscle tissue from each
      individual was assessed for the presence of CTX using two methods: a semi
      quantitative ELISA that was recently developed for detecting picogram levels of
      CTX in fish extract and a neuroblastoma (NB) cell assay commonly used to screen
      for marine toxins in fish. Results of the tests were highly correlated, with the
      ELISA indicating the presence of CTX in 9.4% of all fish samples, and the NB
      assay indicating toxicity in 6.8% of the fish samples. We conclude that the ELISA
      produces reliable and accurate results that are consistent with those provided by
      the accepted NB assay and that the ELISA has potential for future applications in
      screening fish populations for CTX.

PMID- 18623119
TI  - Finding blunders in thyroid testing: experience in newborns.
AB  - We evaluated thyroxin (T4) and thyroid-stimulating hormone (TSH) data along with
      clinical information from 600,000 newborns. We looked for certain combinations of
      tests and clinical data that were questionable and possibly mistaken. Our
      approach suggests that certain combinations of test results, especially the
      presence of missing results deserved further evaluation for possible blunders. We
      found that missing tests were frequently the result of oversight. The laboratory
      used the well-known standard blood-spot-on-filter paper methods for TSH and T4.
      For quantitation of TSH and T4, we used the time-resolved fluoroimmunoassay
      available from Perkin Elmer. We found 56 babies with confirmed primary congenital
      hypothyroidism (PCH) in a total of 600,000 patients. We also found 18 sets of
      results in the same 600,000 babies that gave inconsistent findings, had missing
      values, and (or) possible misinterpretations of the clinical and (or) laboratory
      data. What is an acceptable mistake rate? All mistakes are unacceptable, but
      there is likely some irreducible mistake rate, and efforts to reduce the mistake
      or blunder rate still further may not be cost-effective. What can be done is to
      study the mistake rate per 600,000 babies from year to year; the mistake rate
      should be decreasing or not changing. This assumes a stable cohort of babies; an
      assumption that may be acceptable. We applied a form of pattern recognition to
      identify cases of possible blunders and missing values in either the laboratory
      or clinical data. What is clear is that we apparently identified some blunders.
      The 18 mistakes per 600,000 babies may be "very low" and acceptable. We recommend
      that seeking ever decreasing mistakes is the way to go, and the level of
      monitoring the data should be very intense given the serious consequences of mis
      diagnosed thyroid disorders.

PMID- 18623120
TI  - Nontreponemal tests in the diagnosis of neurosyphilis: an evaluation of the
      Venereal Disease Research Laboratory (VDRL) and the Rapid Plasma Reagin (RPR)
      tests.
AB  - The Venereal Disease Research Laboratory (VDRL) test has long been considered the
      best serological test for the diagnosis of neurosyphilis. The goal of this study
      was to find out if the Rapid Plasma Reagin (RPR) could be an alternative to the
      VDRL. Cerebrospinal fluid (CSF) and sera samples from patients in the following
      stages of syphilis were tested: 8 had symptomatic and 16 asymptomatic
      neurosyphilis, 4 were in the primary stage, 6 had secondary syphilis, and 92 were
      in the latent stage. We have also studied 61 samples from individuals with
      treated syphilis and 126 with other neurological diseases than neurosyphilis. All
      the CSF samples were studied with both RPR and VDRL tests. RPR and VDRL test
      results were mostly concordant. The specificity of these tests for current
      neurosyphilis was 99% for the VDRL and 99.3% for the RPR, whereas the sensitivity
      was 70.8 and 75%, respectively, for the VDRL and RPR. In view of these results it
      seems to us that the RPR could be an alternative to the VDRL in the diagnosis of
      neurosyphilis.

PMID- 18623121
TI  - RNA from Borna disease virus in patients with schizophrenia, schizoaffective
      patients, and in their biological relatives.
AB  - Numerous interactions of the immune system with the central nervous system have
      been described recently. Mood and psychotic disorders, such as severe depression
      and schizophrenia, are both heterogeneous disorders regarding clinical
      symptomatology, the acuity of symptoms, the clinical course, the treatment
      response, and probably also the etiology. Detection of p24 RNA from Borna disease
      virus (BDV) by the reverse transcriptase polymerase chain reaction in patients
      with schizophrenia, schizoaffective disorder, and in their biological relatives
      was evaluated. The subjects were 27 schizophrenic and schizoaffective patients,
      27 healthy controls, 20 relatives without psychiatric disease, and 24 relatives
      with mood disorder, who attended the Psychiatric Ambulatory of Londrina State
      University, Parana, Brazil. The subjects were interviewed by structured
      diagnostic criteria categorized according to the Diagnostic and Statistical
      Manual of Mental Disorders-IV, axis I, (SCID-IV). The mean duration of illness in
      schizophrenic and schizoaffective patients was 15.341+/-1.494 years and the
      median age at onset was 22.4+/-7.371 years. There were no significant differences
      in gender (P=0.297), age (P=0.99), albumin (P=0.26), and body mass index
      (kg/m(2)) (p=0.28), among patients, controls, and relatives. Patients and
      biological relatives had significantly higher positive p24 RNA BDV detection than
      controls (P=0.04); however, the clinical significance of BDV remains to be
      clarified.

PMID- 18623122
TI  - Evaluation of enzyme-linked immunosorbent assays for detecting circulating
      antibodies to Candida albicans.
AB  - Published studies indicate that Candida albicans antibody assays utilizing
      cytoplasmic antigens offer greater utility for identifying cases of systemic
      candidiasis when compared with assays utilizing cell wall components. We assessed
      the performance characteristics of a commercially available system that utilizes
      cytoplasmic antigens to measure C. albicans IgG, IgM, and IgA (Candida Detect
      ELISA reagents). Intra-assay variation was < or =5%, inter-assay variation was <
      or =10%, and good linearity was observed for all the three antibody isotypes.
      Results for specimens stored under various conditions were comparable to those
      obtained initially. Inter-laboratory reproducibility was excellent; qualitative
      concordance was > or =93% for all the three isotypes, with slopes and R(2) values
      approaching 1.0 in linear regression analyses. Seroprevalence in persons without
      apparent systemic candidiasis was evaluated using three different serum panels;
      seroprevalence rates ranged from 24 to 32% for IgG, 2-14% for IgM, and 15-36% for
      IgA. Seroprevalence rates in a panel of sera containing antibodies to other fungi
      were similar to rates observed in panels from individuals without systemic
      candidiasis. These findings demonstrate the acceptable performance of assay
      systems employing Candida Detect ELISA reagents.

PMID- 18623123
TI  - Comparison between a liquid chromatography-tandem mass spectrometry assay and a
      fluorescent polarization immunoassay to measure whole blood everolimus
      concentration in heart and renal transplantations.
AB  - Various methods [fluorescent polarization immunoassay (FPIA) and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) assay] are used for
      therapeutic drug monitoring of everolimus. The aim of this study is to compare
      these assays in renal and heart transplantation. The correlation between results
      was investigated by linear regression in 44 patients (24 heart recipients and 20
      renal recipients--137 samples). The comparison between assays was performed by a
      paired t-test. A highly significant correlation was found between FPIA and LC
      MS/MS in heart and renal recipients [FPIA=0.851 x LC-MS/MS+1.773r(2)=0.8738
      (P<0.001)]. Paired t-tests did not show a significant difference between
      everolimus whole blood concentrations in the populations of heart and renal
      recipients or heart recipients or renal recipients. FPIA and LC-MS/MS assays gave
      consistent overall results although some significant differences were observed in
      some samples between these methods indicating that FPIA assay has limitations
      that deserve further investigations.

PMID- 18623124
TI  - Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine
      Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin
      immunoassay.
AB  - Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha
      demonstrated modest interference with serum digoxin measurements by the
      fluorescent polarization immunoassay (FPIA). Recently, Abbott Laboratories
      marketed a new digoxin immunoassay, Digoxin III for application on the AxSYM
      analyzer. We studied potential interference of these herbal supplements on serum
      digoxin measurement by Digoxin III assay in vitro and compared our results with
      the values obtained by Tina-quant assay. Aliquots of drug-free serum pool were
      supplemented with various amounts of Asian ginseng, Siberian ginseng, or
      Ashwagandha approximating expected concentrations after recommended doses and
      overdoses of these herbal supplements in serum. Then digoxin concentrations were
      measured by the Digoxin III and Tina-quant (Roche Diagnostics) assay. We also
      supplemented aliquots of a digoxin pool prepared from patients receiving digoxin
      with various amounts of these herbal supplements and then measured digoxin
      concentrations again using both digoxin immunoassays. We observed modest apparent
      digoxin concentrations when aliquots of drug-free serum pool were supplemented
      with all three herbal supplements using Digoxin III assay (apparent digoxin in
      the range of 0.31-0.57 ng/ml), but no apparent digoxin concentration (except with
      the highest concentration of Ashwagandha supplement for both brands) was observed
      using the Tina-quant assay. When aliquots of digoxin pool were further
      supplemented with these herbal supplements, digoxin concentrations were falsely
      elevated when measured by the new Digoxin III assay. For example, we observed
      48.2% (1.63 ng/ml digoxin) increase in digoxin concentration when an aliquot of
      Digoxin pool 1 (1.10 ng/ml digoxin) was supplemented with 50 microl of Asian
      ginseng extract (Brand 2). Measuring free digoxin does not eliminate the modest
      interferences of these herbal supplements in serum digoxin measurement by the
      Digoxin III assay.

PMID- 18623125
TI  - Clinical laboratory automated urinalysis: comparison among automated microscopy,
      flow cytometry, two test strips analyzers, and manual microscopic examination of
      the urine sediments.
AB  - Urinalysis is one of the habitual clinical laboratory procedures, which implies
      that one of the largest sample volumes currently requires significant labor to
      examine microscopic sediments. Different analyzers currently used to perform this
      task have been compared with the manual microscopic sediment examination. The
      Atlas Clinitek 10 (Bayer Corporation, Diagnostics Division, Tarrytown, NY) and
      Urisys 2400 (Hitachi Science Systems Ltd., Ibaraki, Japan) test strips analyzers
      and two automated urinalysis systems, Sysmex UF-100 (Sysmex Corporation Kobe,
      Japan) and IRIS iQ200 (International Imaging Remote Systems, Chatsworth, CA),
      have been considered. We assessed the concordance between the results obtained
      from 652 freshly collected urine samples for erythrocytes (RBC), leukocytes
      (WBC), squamous epithelial cells (EC), nitrites/bacteria, and crystals using the
      methodologies mentioned. A principal components analysis was performed in order
      to examine the correlation between these parameters. Instrument accuracy was also
      assessed. The Spearman's statistic (p) showed an adequate agreement between
      methods for RBC (iQ200=0.473; UF-100=0.439; Atlas=0.525; Urisys=0.539), WBC
      (iQ200=0.695; UF-100=0.761; Atlas=0.684: Urisys=0.620), and bacteria/nitrites
      (iQ200=0.538; UF-100=0.647; Atlas=0.532; Urisys=0.561) counts. By applying the
      Wilcoxon and McNemar tests, a concordance degree was found between 82-99 and 52
      95% for the values obtained from the two test strips analyzers considered and
      from the iQ200 and UF-100 systems, respectively. From these results, we can
      conclude that both test strips analyzers are similar and, on the other hand, that
      automated urinalysis is needed to improve precision and the response time; but
      sometimes manual microscopic revisions are required, mainly when flags, because
      of crystals, are detected.

PMID- 18623126
TI  - CHFR expression is preferentially impaired in smoking-related squamous cell
      carcinoma of the lung, and the diminished expression significantly harms
      outcomes.
AB  - Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis.
      Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key
      regulators of mitosis, has been detected in a variety of solid tumors. Recently,
      CHFR has been revealed to ensure chromosomal stability by controlling the
      expression level of Aurora-A in vitro. However, the frequency of aberrant
      expression of these proteins and the association with clinicopathologic
      parameters remain poorly defined in nonsmall-cell lung cancer (NSCLC). In this
      study, we investigated the immunohistochemical protein expression of CHFR and
      Aurora-A in 157 NSCLC cases and evaluated the association between
      clinicopathologic parameters statistically. The relationship between CHFR protein
      and mRNA levels and the association between this relationship and promoter
      methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC.
      Overexpression of Aurora-A and reduced expression of CHFR were found in 94 cases
      (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly
      correlated with tumor differentiation and size. Moreover, diminished CHFR
      expression was significantly associated with smoking-related squamous cell
      carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR
      expression was an independent prognostic factor. A statistical correlation was
      evident between CHFR protein and mRNA expression. In conclusion, our results
      suggest the aberrant expression of Aurora-A and/or of CHFR contributed to the
      increase in the malignant potential of NSCLC. We also revealed that CHFR
      expression was predominantly impaired in smoking-related squamous cell carcinoma
      and might be a useful prognostic marker in NSCLC.

PMID- 18623127
TI  - Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism
      in JAK2 wild type myeloproliferative diseases.
AB  - In polycythemia vera (PV) and essential thrombocythemia (ET) specific JAK2
      mutations constitutively activate the JAK-STAT pathway, explaining biologic
      findings such as endogenous erythroid colony (EECs) growth or PRV-1 RNA
      overexpression. Since these markers are detected also in JAK2 wild type patients,
      we hypothesized that, in these cases, the activation of the JAK-STAT pathway
      could be produced by a deregulation of the suppressor of cytokine signaling
      (SOCS) protein system. Eighty-one patients with PV and ET (53 adults and 28
      children) were investigated for the methylation status of the SOCS-1, SOCS-2 and
      SOCS-3 CpG islands and for several myeloproliferative markers (including JAK2 and
      MPL mutations and clonality of hematopoiesis). SOCS-1 or SOCS-3 hypermethylation
      was identified in 23 patients and was associated with a significant decrease of
      SOCS-1 or SOCS-3 RNA and protein levels. The gene expression was restored by
      exposing cells to the demethylating agent 2-deoxyazacytidin. Interestingly, SOCS
      1 or SOCS-3 hypermethylation was detected in 6 female patients, proved negative
      for JAK2 or MPL mutations and exhibiting monoclonal hematopoiesis. In conclusion,
      SOCS-1 or SOCS-3 hypermethylation can activate the JAK-STAT signaling pathway in
      alternative or together with JAK2 mutations. These alterations might represent a
      potential therapeutic target.

PMID- 18623128
TI  - Host and viral factors in relation to clearance of human papillomavirus
      infection: a cohort study in Taiwan.
AB  - Human papillomavirus (HPV) persistence is essential for cervical cancer
      development. We accrued nested-cohort subjects from a population-based study to
      investigate the host and viral factors related to outcome of HPV infection. Women
      (age > or = 30 years old) with HPV-positive but normal cytology and negative
      colposcopy were invited to participate. After signing informed consent, every
      participant completed a structured questionnaire and had 6-monthly follow-ups of
      Pap smear, HPV testing and colposcopy. Total and type-specific HPV clearance
      rates as well as host and viral factors associated with clearance in 3-year
      longitudinal follow-up were analyzed. Adjusted hazard ratios (HRs) of progression
      to > or = cervical intraepithelial neoplasia (CIN) 2 according to baseline HPV of
      the women with normal cytology were calculated from national registry database.
      Among the 626 eligible women, 526 (median age 47, 29-75) were enrolled and 412
      returned for follow-up at least once. The median follow-up of enrolled subjects
      was 23 months (range 6.8-39). The 3-year cumulative total HPV clearance rate was
      49.0% (95% confidence interval [CI]: 43.3-54.7%). The median 3-year cumulative
      type-specific HPV clearance rate was 50.0% (range 0-100.0%) with a median time to
      clearance of 12.4 months (6.4-24.5). Older age was associated with significantly
      decreased total HPV clearance and decreased type-specific clearance in HPV-18 and
      -53, while high viral load was associated with decreased total and type-specific
      clearance. After adjusting confounding variables, the HR of developing > or =CIN2
      in baseline HPV-positive women was 34.0-fold (95% CI: 15.5-74.7) as compared to
      HPV-negative women.

PMID- 18623129
TI  - Inhibition of epidermal growth factor receptor signaling pathway by delphinidin,
      an anthocyanidin in pigmented fruits and vegetables.
AB  - Inhibitors of the epidermal growth factor receptor (EGFR) have generated
      considerable hope for cancer treatment, specifically for lung and breast cancers.
      Therefore, identification of a natural, nontoxic agent(s) as an inhibitor of EGFR
      is of considerable importance. Delphinidin, an anthocyanidin present in pigmented
      fruits and vegetables, possesses potent antioxidant and antiproliferative
      properties. In our study, employing EGFR positive breast cancer AU-565 cells and
      immortalized MCF-10A cells, we evaluated the effect of delphinidin on EGFR and
      its downstream signaling pathways. Delphinidin (5-40 microM; 3 hr) treatment of
      both AU-565 cells and MCF-10A cells inhibited the (i) phosphorylation of EGFR,
      (ii) activation of PI3K, (iii) phosphorylation of AKT and MAPK. Further,
      delphinidin treatment of AU-565 cells inhibited EGF-induced autophosphorylation
      of EGFR, AKT and MAPK, activation of PI3K and cell invasion. We then compared the
      growth inhibitory effects of delphinidin (5-40 microM; 48 hr), and found that it
      resulted in a decrease in cell growth of AU-565 and MCF-10A cells but had only
      minimal effects on normal mammary epithelial 184A1 cells. Treatment of AU-565
      cells with delphinidin resulted in (i) induction of apoptosis, (ii) cleavage of
      PARP protein, (iii) activation of caspase-3 and (iv) downregulation of Bcl-2 with
      an increase in the expression of Bax. In summary, our study identifies a
      naturally occurring dietary agent delphinidin as an effective inhibitor of EGFR
      signaling in breast cancer cells. We suggest that delphinidin could be developed
      as an agent for the management of EGFR positive human cancers.

PMID- 18623131
TI  - A compendium of familial relative risks of cancer among first degree relatives: a
      population-based study.
AB  - Familial clustering of cancer is expected to occur at practically all anatomical
      sites. However, few studies have had sufficient size to investigate different
      sites simultaneously and with adjustment for confounders. We evaluated familial
      clustering in the Netherlands Cohort Study in which 120,852 men and women, aged
      55-69 years in 1986 were followed up for 13.3 years. 14,025 Probands, 6,629
      parents and 4,271 siblings were diagnosed with cancer. Relative Risks (RR) of
      cancer in first degree family members were calculated by using multivariable Cox
      regression analyses. We also calculated false-positive reporting probabilities.
      Significant concordant familial clustering was observed for stomach (RR(father) =
      1.89, RR(parent) = 1.66, RR(sister) = 3.33, RR(sibling) = 2.38, RR(1st degree) =
      1.69), colon/rectum (RR(father) = 1.82, RR(mother) = 1.83, RR(parent) = 1.88,
      RR(1st degree) = 1.56), lung (RR(brother) = 1.50) and breast cancer (RR(mother) =
      1.65, RR(sister) = 1.72, RR(1st degree) = 1.72) with low false-positive reporting
      probabilities. Significant discordant familial clustering has been observed for
      combinations of pancreas-colon/rectum (RR(mother) = 2.42, RR(parent) = 1.89,
      RR(1st degree) = 1.73), larynx-lung (RR(father) = 3.35, RR(parent) = 2.84, RR(1st
      degree) = 2.30), lung-oesophagus (RR(sibling) = 3.49), breast-bladder (RR(father)
      = 2.79, RR(parent) = 2.61), endometrium-stomach (RR(mother) = 2.32), ovarium
      oesophagus (RR(1stdegree) = 4.19), prostate-colon/rectum (RR(parent) = 1.46) and
      bladder-larynx/pharynx (RR(father) = 2.49) cancer, although false-positive
      reporting probabilities were higher for these associations. Familial clustering
      of cancer occurs at most sites but is generally modest. Some observed discordant
      familial clustering is surprising but should be interpreted with caution as their
      prior probability is low.

PMID- 18623130
TI  - Trends in incidence and mortality of thyroid carcinoma in The Netherlands between
      1989 and 2003: correlation with thyroid fine-needle aspiration cytology and
      thyroid surgery.
AB  - A persistent increase in incidence of thyroid carcinoma (TC) has been reported
      worldwide. The aim of our study was to assess trends in incidence and mortality
      of TC in The Netherlands between 1989 and 2003 and to examine whether these
      trends correlate with changes in diagnostic practices such as changes in the
      number of fine needle aspiration biopsies (FNAB) and/or thyroid surgeries.
      Population-based incidence and mortality data were retrieved from the Netherlands
      Cancer Registry. Data concerning FNAB and thyroid surgeries were obtained through
      the nationwide network and registry of histo- and cytopathology in The
      Netherlands (PALGA). Overall, the incidence of TC remained unchanged. However,
      there was a slight increase in incidence of papillary TC of 2.1% per year (p <
      0.001) particularly in stage I tumors, possibly, in part, because of a marked
      increase in use of FNAB. Appropriate iodine intake, reduced radiation exposure
      and a more conservative diagnostic approach toward asymptomatic thyroid nodules
      may explain why this increase is less pronounced compared to other countries.
      Incidence of other subtypes of TC decreased (follicular TC, 1.3% per year, p =
      0.02 and anaplastic TC, 7.1% per year, p = 0.006) or remained unchanged
      (medullary TC). The number of FNABs per year progressively increased from 1,093
      in 1989 to 4,123 in 2003, whereas the number of thyroid surgeries decreased from
      3,419 in 1989 to 2,825 in 2003. The mortality rates decreased by 2.3% per year (p
      = 0.01). The decrease in incidence of both follicular and anaplastic TC is
      assumed to be largely responsible for the decrease in TC mortality rates.

PMID- 18623132
TI  - Paracrine inhibition of osteoblast differentiation induced by neuroblastoma
      cells.
AB  - The aim of our study was to investigate whether the defective function of
      osteogenic cells induced by neuroblastoma might play a role in the development of
      skeletal metastases. This mechanism has been extensively demonstrated for
      multiple myeloma, in which the blockage of osteoblast differentiation has been
      ascribed to the inhibitors of canonical Wingless pathway (Wnt), namely Dickkopf 1
      (Dkk1). Our purpose was to verify if neuroblastoma cells derived from bone marrow
      metastases (SH-SY5Y, LAN1) or primaries (NB100, CHP212) hamper the
      differentiation of mesenchymal stem cells (hMSCs) into osteoblasts in a paracrine
      manner, and to test whether this ability depends on Dkk1 activity. We found that
      all neuroblastoma cells increased the proliferation of hMSCs collected from
      pediatric-aged donors, with a corresponding decrease in osteoblast
      differentiation markers, including alkaline phosphatase (ALP), analyzed as gene
      expression, enzymatic activity and number of ALP-positive colony forming units,
      osteoprotegerin (OPG) release, OPG and osteocalcin gene-expression. Dkk1 mRNA and
      protein were detectable in all cell lines, and the use of neutralizing anti-Dkk1
      antibody reversed the effects induced by SH-SY5Y cells. Taken together, our
      results confirm that neuroblastoma hinders osteoblastogenesis, and that Dkk1
      release seems to play a crucial role in blocking the differentiation of
      osteoprogenitor cells, though the ability to promote osteoclast activation
      remains an essential requirement for the development of skeletal metastases.
      Finally, our findings suggest that strategies regulating Wnt signaling and Dkk1
      activity could be considered for adjuvant therapies in neuroblastoma
      metastasizing to the skeleton.

PMID- 18623133
TI  - Association study of CCR5 delta 32 polymorphism among the HLA-DRB1 Caucasian
      population in Northern Parana, Brazil.
AB  - Chemokines are important determinants of early inflammatory response. The CC
      chemokine receptor 5 (CCR5) delta 32 variant results in a nonfunctional form of
      the chemokine receptor and has been implicated in a variety of immune-mediated
      diseases. In the present study, polymerase chain reaction (PCR) for genomic
      deoxyribonucleic acid (DNA) samples, using specific CCR5 oligonucleotide primers
      surrounding the breakpoint deletion, detected a 225-basepair (bp) product from
      the normal CCR5 allele and a 193-bp product from the 32 bp deletion allele. Human
      leukocyte antigen (HLA) class II (DRB1) typing was performed by PCR-sequence
      specific primer (PCR-SSP). The aim of this study was to evaluate the association
      of HLA-DRB1 and CCR5 genetic polymorphisms. To evaluate the frequency
      distributions of CCR5 delta 32 polymorphisms in a Brazilian population and their
      association with allelic distribution of HLA genes, DRB1; a total of 120
      Caucasian individuals from northern Parana, Brazil, were tested. The CCR5/CCR5
      genotype was found in 108 individuals (90%) and only one carried the CCR5 delta
      32 allele homozygous genotype (0.0238), while 12 (10%) carried the CCR5 delta 32
      allele heterozygous genotype. The observed frequency for the CCR5 delta 32 allele
      was 0.05 in the population studied. The results revealed a CCR5 delta 32 allele
      occurrence with HLA-DRB1(*)01 and DRB1(*)04 (P<0.05). It is possible that HLA
      DRB1(*)01 and DRB1(*)04 alleles could be associated with the delta 32-bp deletion
      of CCR5.

PMID- 18623134
TI  - Development of an enzyme-linked immunosorbent assay for the detection of
      ciguatoxin in fish tissue using chicken immunoglobulin Y.
AB  - A sandwich enzyme-linked immunosorbent assay was developed to detect ciguatoxin
      (CTX) in fish tissue. The assay utilizes two antibodies, chicken immunoglobulin Y
      specific to the ABCD domain of CTX and a mouse monoclonal immunoglobulin G
      horseradish peroxidase conjugate specific to the JKLM domain of CTX. The
      sensitivity, working range, cross reactivity, accuracy, precision, and
      reproducibility were examined.

PMID- 18623135
TI  - Heritabilities of somatotype components in a population from rural Mozambique.
AB  - There have been few genetic studies of normal variation in body size and
      composition conducted in Africa. In particular, the genetic determinants of
      somatotype remain to be established for an African population. (1) To estimate
      the heritabilities of aspects of somatotype and (2) to compare the quantitative
      genetic effects in an African population to those that have been assessed in
      European and American populations. The sample composed of 329 subjects (173 males
      and 156 females) aged 7-17 years, belonging to 132 families. The sibships in the
      sample ranged in size from two to seven individuals. All sampled individuals were
      residents of the Calanga region, an area located to the north of Maputo in
      Mozambique. Somatotype was assessed using the Heath-Carter technique. Herit
      abilities were estimated using SAGE software. Moderate heritabilities were
      determined for each trait. Between 30 and 40% of the variation in each somatotype
      measure was attributable to genetic factors. The heritability of ectomorphy was
      31%. Mesomorphy was similarly moderately heritable, with approximately 30% of the
      variationattributable to genetic factors. The heritability of endomorph was
      higher in the Calanga population (h(2) = 0.40). Quantitative genetic analyses of
      somatotype variation among siblings indicate that genetic factors significantly
      influence endomorphy, mesomorhpy, and ectomorphy. However, environmental factors
      also have significant effects on the variation in physique present in the
      population of Calanga. Lack of proper nutrition, housing, medical assistance, and
      primary health care, together with very demanding and sex-specific daily chores
      may contribute to the environmental effects on these traits.

PMID- 18623137
TI  - Surfactant-Modified lipase for the catalysis of the interesterification of
      triglycerides and fatty acids.
AB  - The lipase-catalyzed intresterification of triglycerides and fatty acids in n
      hexane was studied. Initially, lipase Saiken was modified with a surfactant of
      sorbitan esters so that its dispersibility in hydrophobic organic media was
      improved. The surfactant-modified lipase formed in the modification process
      carried out in a buffer solution has 1,3-positional specificity and predominantly
      catalyzed the interesterification reaction in a microaqueous n-hexane system. The
      modification technique converted inactive lipases to very active biocatalysts for
      the interesterification of triglycerides and fatty acids. The pH and the weight
      ratio of surfactant to enzyme used during the lipase modification process have
      shown significant effects in determining the recoveries of the protein and enzyme
      activity from the buffer solution, the protein content of the modified lipase
      complex after being freeze dried, and the interesterification activity of the
      complex. The water content in the reaction solution has strongly influenced the
      enzyme activity as well as the distribution of the products. (c) 1995 John Wiley
      & Sons, Inc.

PMID- 18623138
TI  - Characterization of tryptic casein phosphopeptides prepared under industrially
      relevant conditions.
AB  - Anticariogenic casein phosphopeptides (ACPP) contain the cluster sequence -Ser(P)
      Ser(P)-Ser(P)-Glu-Glu- and have commercial potential as toothpaste, mouthwash,
      and food additives for the prevention of dental caries. In an approach to develop
      a commercial-scale process for the production of ACPP we have comprehensively
      characterized casein phosphopeptides (CPP) produced under industrially relevant
      conditions. Sodium caseinate (10% w/v) was hydrolyzed by Novo trypsin (commercial
      grade) at 50 degrees C for 2 h and CPP were purified from the acid clarified
      hydrolysate by a single-step selective precipitation procedure involving Ca(2+)
      (20 mol/mol casein) and ethanol (50% v/v) at pH 4.6 or 8.0. The individual
      peptides of the CPP preparations were purified by reversed-phase high-performance
      liquid chromatography (HPLC) and then identified by amino acid composition and
      sequence analyses. The yield of the pH 8.0 precipitate (13.85 +/- 0.48 wt % of
      the caseinate) was slightly higher than that of the pH 4.6 precipitate (11.04 +/-
      0.30 wt % of the caseinate). However, the pH 4.6 precipitate contained
      predominantly (86.4 mol %) ACPP cluster peptides with small amounts of the
      diphosphorylated peptides (13.6 mol %), alpha(s1)(43-58) and alpha(s2)(126-136).
      In the pH 8.0 precipitate the cluster peptides represented a smaller proportion
      of the total peptides (61.9 mol %) due to increased recoveries of the
      diphosphorylated peptides (24.4 mol %) as well as the additional recovery of the
      monophosphorylated peptide beta(33-48) (13.7 mol %) indicating increased cross
      linking by Ca(2+) at the higher pH. The recovery of the ACPP from the original
      caseinate was similar for both the pH 4.6 and 8.0 precipitates. Slight
      chymotryptic activity was detected in the industrial-grade enzyme, resulting in
      minor truncation of some peptides. Also some deamidation and methionine oxidation
      of one peptide, alpha(s1)(59-79), were detected. In conclusion, ACPP can be
      produced under industrially relevant conditions with only minor modifications
      such as slight truncation, deamidation, and methionine oxidation. However, in
      order to prepare casein phosphopeptides predominantly containing the cluster
      sequence -Ser(P)-Ser(P)-Ser(P)-Glu-Glu-, the single-step selective precipitation
      with Ca(2+)/ethanol should be performed at pH 4.6 rather than pH 8.0. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623139
TI  - Purification of monoclonal antibodies from whole hybridoma fermentation broth by
      fluidized bed adsorption.
AB  - To achive the coarse purification of a monoclonal antibody from whole hybridoma
      fermentation broth a fluidized bed cation exchange process was used. The
      procedure consisted of application of the crude sample and washing of the bed in
      a fluidized mode and elution in a fixed bed mode. A completely clarified eluate
      was obtained with purification factors between 4 and 8 and a concentration of the
      desired product (monoclonal antibody) by a factor of more than 3 was achived.
      Thus, a combination of the three early steps of the downstream process
      clarification, concentration and coarse purification was possible. Two different
      materials were tested: a commercially available agarose-based matrix (Stream-line
      SP), and a self-derivatized material based on controlled-pore glass (Bioran).
      Initial experiments were performed to describe the fluidization of the glass
      material. Comparison with the agarose material showed several differences, the
      agarose matrix allowing liquid flow closer to plug flow than the glass material.
      Increased backmixing in the liquid phase was detected when fluidizing the glass
      adsorbent compared with the agarose-based matrix. Despite this fact, comparison
      of the two materials with respect to antibody binding and elution demonstrated a
      similar performance. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623140
TI  - Effects of calcium on development of anaerobic acidogenic biofilms.
AB  - Anerobic biofilms with dominantly acidogenic bacteria were grown in fixed-bed
      recycle reactors. The influence of calcium concentration in the culture medium on
      biofilm mass accumulation, immobilized calcium concentration, and biofilm
      specific activity was investigated. The results indicate that the biofilm mass
      accumulation was increased by the presence of calcium in the growth medium when
      calcium concentration was not higher than 120mg/L. Calcium accumulated in the
      biofilms increased in proportion to the calcium level in the feed. The biofilms
      for an increased input calcium concentration showed a trend of decrease in
      specific activity. The biofilms with a thickeness of less than 0.5 mm had the
      highest specific activity. The optimum calcium concentration for substrate
      consumption by the biofilms was 100 to 120 mg/L. The biofilms transferred from
      higher calcium medium to lower calcium medium were more susceptible to sloughing
      from their support surfaces, which indicates calcium's role in the stability of
      the biofilm structure. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623141
TI  - Modeling of anaerobic formate kinetics in mixed biofilm culture using dynamic
      membrane mass spectrometric measurement.
AB  - The dynamics of the anaerobic conversion of formate in a microbial mixed culture
      taken from an anaerobic fluidized bed reactor was studied using a new stirred
      micro reactor equipped with a membrane mass spectrometer. The microreactor with a
      toroidally shaped bottom and pitched blade turbine and a cylindrical flow guide
      was thermostated and additionally equipped with a pH electrode and pH control.
      During fed-batch experiments using formate, the dissolved gases (methane,
      hydrogen, and carbon dioxide), as well as the acid consumption rates for pH
      control were monitored continuously. Initially and at the end of each experiment,
      organic acids were analyzed using ion chromatography (IC). It was found that
      about 50% of the formate was converted to methane via hydrogen and carbon
      dioxide, 40% gave methane either directly or via acetate. This was calculated
      from experiments using H(13)CO(3) (-) pulses and measurement of (12)CH(4) and
      (13)CH(4) production rates. About 10% of the formate was converted to lactate,
      acetate, and propionate, thereby increasing the measured CO(2)/CH(4) production
      ratio. The nondissociated formic acid was shown to be rate determining. From the
      relatively high K(s) value of 2.5 mmol m(-3), it was concluded that formate
      cannot play an important role in electron transfer. During dynamic feeding of
      formate, hydrogen concentration always increased to a maximum before decreasing
      again. This peak was found to be very discriminative during modeling. From the
      various models set up, only those with two-stage degradation and double Monod
      kinetics, both for CO(2) and hydrogen, were able to describe the experimental
      data adequately. Additional discrimination was possible with the IC measurement
      of organic acids. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623142
TI  - Batch cultivation of Methylosinus trichosporium OB3B: IV. Production of hydrogen
      driven soluble or particulate methane monooxygenase activity.
AB  - Batch culture conditions were established for the formation of H(2)-driven whole
      cell soluble or particulate methane monooxygenase (sMMO or pMMO) activity in the
      obligate methanotroph, Methylosinus trichosporum Ob3b, to expand its potential
      uses in groundwater bioremediation and the production of specific chemicals.
      Addition of either Ni and H(2) to a nitrate-containing minimal salts growth
      medium or Ni and Mo to a nitrate-lacking growth medium (induces a nitrogenase
      that generates intracellular H(2)) markedly enhanced both the hydrogenase and the
      accompanying washed-cell H(2)-driven MMO activities of shake-flask cultured
      cells. For sMMO containing cells, H(2) provided in vitro reducing power for the
      oxidation of chlorinated solvents such as chloroform and trichloroethylene. Cell
      cultivations under N(2)-fixing conditions in a 5-L bioreactor, however, required
      an initial nitrate concentration of at least 1 to 2 mM to achieve high biomass
      yields (5 to 7 g of dry cell wt/L) for cells producing H(2)-driven sMMO or pMMO
      activity. Elevation of the initial medium nitrate concentration to 20 mM
      shortened the culture time for pMMO producing cells by 40%, yet still generated
      an equivalent growth yield. High nitrate also shortened the culture time for sMMO
      containing cells by approximately 25%, but it lowered their biomass yield by 26%.
      Upon storage for 5 weeks at room temperature, washed resting-state cells retained
      90% and 70% of their H(2)-driven sMMO and pMMO activity, respectively. This makes
      their practical use quite feasible. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623143
TI  - Effect of surfactant and particle size reduction on hydrolysis of deinking sludge
      and nonrecyclable newsprint.
AB  - Disposal of sludge from deinking mills represents a significant proportion of
      operating costs. Bioconversion of the cellulosic fraction of deinking sludge
      (DIS) to ethanol greatly reduces disposal costs while producing an
      environmentally friendly fuel. In this study, the cellulosic fraction of
      newsprint and deinking sludge was hydrolysed to produce fermentable sugars. For
      newsprint, a particle size of 1 to 1.5 mm provided optimal reaction rates in
      batch reactors over practical hydrolysis times, and reducing sugar concentrations
      as high as 35 g/L could be achieved using a fed-batch reactor configuration. For
      both newsprint and DIS, the hydrolysis rate increased nonlinearly with enzyme
      loading. Tween-80 only marginally improved sugar production but was able to
      release sugars from cellulosic substrates in the absence of lytic enzymes, in an
      amount proportional to the surfactant concentration and the substrate particle
      size. DIS was relatively recalcitrant to enzymatic hydrolysis, possibly due in
      part to inhibition by hydrophobic constituents. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623144
TI  - High cell density fermentation of recombinant Vibrio cholerae for the production
      of B subunit of Escherichia coli enterotoxin.
AB  - High cell density fermentation studies were performed to produce the B subunit of
      Escherichia coli heat-labile enterotoxin (LTB) from a Vibrio cholerae culture
      that carries a recombinant plasmid with an ampicillin resistance gene, tac
      promoter, and the gene encoding LTB. Upon induction with isopropyl-beta-D
      thiogalactopyranoside (IPTG) the culture secreted the protein into the
      extracellular milieu. Fed-batch fermentation with stepwise addition of a total of
      5 mM of IPTG during the active growth phase of the organism resulted in the
      production of 400 mg/L of LTB in 9 h and a cell optical density (OD) of 24. The
      LTB was purified to homogeneity with 70% recovery from the fermentation broth and
      was found to be chemically and biologically identical to the native protein by N
      terminal amino acid sequencing and receptor binding assay. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623145
TI  - Photolithotrophic cultivation of Laminaria saccharina gametophyte cells in a
      stirred-tank bioreactor.
AB  - Filamentous cell cultures derived from female gametophytes of the temperate brown
      macroalga Laminaria saccharina were photolithotrophically cultivated in
      artificial seawater medium within an illuminated 1.3-L stirred-tank bioreactor at
      13 degrees C using CO(2) in air as the carbon source. A Monod model adequately
      described light-saturated growth. The apparent half-saturation constant (K(o))
      was 23 muE/m(2)-s, and maximum specific growth rate was 0.15 day(-1). At a
      constant inoculation cell density of 50 mg DCW/L, biomass productivity after 26
      days of cultivation increased from 630 mg DCW/L at 18 muE/m(2)-s to 890 mg DCW/L
      at 228 muE/m(2)-s. At 98 muE/m(2)-s, 1.1 vvm aeration rate, and 250 rpm impeller
      speed, the CO(2) transfer rates (CO(2) TRs) and CO(2) consumption rates (r(co(2)
      )) were determined over the cultivation period. At peak CO(2) demand, the maximum
      CO(2) TR was 0.19 mmol CO(2)/L-h, but r(co(2) ) was only 0.15 mmol CO(2)/L-h,
      implying that the culture was not CO(2) transport limited. This is the first
      reported bioreactor cultivation study of cell cultures derived from a macrophytic
      marine alga. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623146
TI  - Enzyme catalyzed biotransformations in aqueous two-phase systems with
      precipitated substrate and/or product.
AB  - Biotransformations catalyzed by free and immobilized enzymes have been carried
      out in aqueous suspensions with up to 25% (w/w) precipitated substrate or
      product. For the kinetically controlled synthesis of N-Acetyl-Tyr-Arg-NH(2) with
      up to 0.8 M insoluble activated substrate N-Acetyl-TyrOEt catalyzed by alpha
      chymotrypsin (EC3.4.21.1) the dipeptide yield was found to be >90%. This and the
      space-time yields were higher than those observed for one-phase aqueous systems
      and much higher than in systems where the insoluble substrate had been
      solubilized by addition of organic solvents. In the equilibrium controlled
      hydrolysis of 0.4 M D-phenylglycine-amide catalyzed by immobilized penicillin
      amidase (EC 3.5.1.11) the product precipitates. The enzyme immobilized in the
      support with the smallest pores could be reused without reduction in the rate due
      to precipitation in the pores. This decreases the number of immobilized enzyme
      molecules that can be used as biocatalysts. The latter was observed for supports
      with larger pores as the solubility decreases with increasing particle size.
      These results demonstrate that biotransformations with insoluble substrates or
      products using free or immobilized enzymes can be easily carried out in aqueous
      two-phase systems, without organic solvents, provided that the pore sizes of the
      supports are sufficiently small and that the rate of mass transfer from the
      precipitated substrate is large. The latter increases with decreasing particle
      size. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623147
TI  - Production of poly(D-3-hydroxybutyrate) from CO(2), H(2), and O(2) by high cell
      density autotrophic cultivation of Alcaligenes eutrophus.
AB  - Hydrogen-oxidizing bacterium, Alcaligenes eutrophus autotrophically produces
      biodegradable plastic material, poly(D-3-hydroxybutyrate), P(3HB), from carbon
      dioxide, hydrogen, and oxygen. In autotrophic cultivation of the microorganism,
      it is essential to eliminate possible occurrence of gas explosions from the
      fermentation process. We developed a bench-plant scale, recycled-gas, closed
      circuit culture system equipped with several safety features to perform
      autotrophic cultivation of A. eutrophus by maintaining the oxygen concentration
      in the substrate gas phase below the lower limit for a gas explosion (6.9%). The
      culture vessel utilized a baskettype agitator, resulting in a K(L) a value of
      2970 h(-1). Oxygen gas was also directly fed to the fermentor separately from the
      other gases. As a result, 91.3 g . dm(-3) of the cells and 61.9 g . dm(-3) of
      P(3HB) were obtained after 40 h of cultivation under this oxygen-limited
      condition. The results compared favorably with those reported for mass production
      of P(3HB) by heterotrophic fermentation. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623148
TI  - Enzymic peptide synthesis in microaqueous, solvent-free systems.
AB  - Thermolysin-catalyzed (EC 3.4.24.4) and chymotrypsin-catalyzed (EC 3.4.21.1)
      peptide synthesis reactions were accomplished without any organic solvent in the
      presence of low amounts of water under sonication and fluidization. The systems
      used are considered to be microaqueous solvent-free ones. The influence of
      several reaction parameters, such as time, the amount of enzyme, the amount of
      water in free form or bound as hydration water, and the N/C component ratio, on
      the vield of the thermolysin-catalyzed synthesis of Z-Phe-Leu-NH(2) (up to 87%
      yield) was investigated in a sonicated system. Besides Z-Phe-Leu-NH(2), the
      tripeptide derivatives Ac-Xaa-Trp-Leu-NH(2), (Xaa = Gly, Ala) were also obtained
      in good yields of 79 and 71% respectively. In the latter case, no hydrolytic side
      reactions were observed. Using a fluidized-bed reactor, chymotrypsin- and
      thermolysin-catalyzed syntheses of N-protected di- and tripeptide amides could be
      perfromed with yields in the range of 10 to 40%. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623149
TI  - Kinetics of nitrate inhibition of carbon tetrachloride transformation by a
      denitrifying consortia.
AB  - The kinetics of nitrate inhibition of carbon tetrachloride (CT) transformation
      were examined using a denitrifying consortium. Comparison of data from fed-batch
      experiments to the model reported by Hooker et al. indicate that the inhibition
      constant ranges between 3.2 and 21 mg/L, with an average of 8.8 mg/L. This range
      is much lower than the previously reported value of 169 mg/L. Simulations using
      the corrected parameter accurately reflect this new data and the data reported by
      Hooker et al. In contrast, the earlier reported coefficient value does not
      reflect the data reported in this work. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623150
TI  - Effect of adrenergic stimulation on cutaneous microcirculation immediately after
      surgical adventitiectomy in a rat skin flap model.
AB  - Chronic sympathetic denervation leads to the development of supersentivity to
      adrenergic agents. Free flap surgery results in the disruption of the autonomic
      nerve fibers running along the anastomosed vessels. We therefore investigated the
      early effect of surgical sympathectomy on the reactivity of cutaneous
      microcirculation challenged to adrenergic agents. Two epigastric flaps were
      elevated and exposed in 15 rats. On the right flap (Side A), a circular
      adventitiectomy of the feeder vessels was realized to provide surgical
      sympathectomy. On the left flap (Side N), vessels were kept intact. The following
      drugs were then given intravenously successively: phenylephrine (10 and 15 microg
      kg(-1)), norepinephrine (10 microg kg(-1)), prazocin (1 mg kg(-1)) followed by
      norepinephrine (10 microg kg(-1)). Cutaneous microcirculation was assessed using
      Laser-Doppler Flowmeters simultaneously on the two flaps after each drug
      administration. Mean arterial pressure was also measured. On side N,
      phenylephrine and norepinephrine resulted in a transient increase in cutaneous
      microcirculation followed by a more prolonged reduction. On side A, only the
      initial increase was observed, which was greater and longer as compared with side
      N, and paralleled the increase in mean arterial pressure. After prazocin pre
      treatment, norepinephrine produced a transient increase in cutaneous
      microcirculation similar on both sides, and parallel to the changes in arterial
      pressure. No decrease in cutaneous microcirculation was observed. Immediately
      after surgical adventitiectomy, the vasoconstriction produced by alpha-adrenergic
      agents is prevented. No denervation-induced hypersentivity is observed. Surgical
      sympathectomy might protect cutaneous flaps from vasoconstriction induced by
      endogenous catecholamines release.

PMID- 18623151
TI  - Isometric tetanic force measurement method of the tibialis anterior in the rat.
AB  - Tetanic force measurements of rat tibialis anterior (TA) muscles have been
      described, but with a variety of stimulation parameters. This study presents a
      novel functional method of force measurement of the rat TA muscle and describes
      the optimization of stimulation parameters. Bilateral TA muscles in 10 male Lewis
      rats were attached to a force transducer after the corresponding hindlimb was
      fixed. Preload, stimulus intensity, duration, and frequency were optimized for
      each individual muscle and the isometric maximal tetanic muscle force was
      measured. The mean left side tetanic force as a percentage of the right was 100.0
      +/- 4.4% and was statistically equivalent. Large standard deviations between
      sides (35-50%) were observed in the optimized parameters (preload, stimulus
      intensity, duration, and frequency). Optimization of the variables affecting
      isometric tetanic force resulted in reproducible and reliable side-to-side
      measurements of the TA muscle in the rat model.

PMID- 18623152
TI  - Technique for determining when plantar heel pain can be neural in origin.
AB  - The surgeon doing microsurgery will encounter problems related to the heel not
      only in terms of how to reinnervate the transferred tissue, but also in patients
      presenting with heel pain. While most heel pain is thought to be related to the
      plantar fascia arising from the calcaneus, conceptually heel pain can be of
      neural origin. The technique for documenting sensibility in the heel is described
      using the Pressure-Specified Sensory Device. Knowledge of calcaneal nerve
      sensibility can determine whether there is sufficient sensation to prevent
      ulceration, whether there is a nerve entrapment that would benefit from
      neurolysis, or whether there is a neuroma that would benefit from resection.

PMID- 18623153
TI  - A massive arterial thrombosis of a free anterolateral thigh flap in a patient
      with antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is a pathological condition characterized by
      recurrent thrombotic manifestations in venous and/or arterial vascular systems
      and by peculiar laboratory findings as anticardiolipin antibodies and/or positive
      lupus anticoagulant. We present a case of massive pedicle thrombosis of a free
      anterolateral thigh perforator flap used for tongue reconstruction following
      hemiglossectomy in a patient with antiphospholipid syndrome, which compelled us
      to an immediate second reconstruction choice with a radial forearm free flap.
      This case is an example of how this syndrome, especially if unknown before
      surgery, can influence the outcome of microsurgical transfer of flaps.

PMID- 18623154
TI  - Effects of glutamine on proinflammatory gene expression and activation of nuclear
      factor kappa B and signal transducers and activators of transcription in TNBS
      induced colitis.
AB  - BACKGROUND: We investigated the effects of glutamine on proinflammatory gene
      expression and activation of nuclear factor kappa B (NF-kappaB) and signal
      transducers and activators of transcription (STAT) in a rat model of experimental
      colitis. METHODS: Colitis was induced in male Wistar rats by intracolonic
      administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Glutamine
      (25 mg/kg) was given by rectal route daily for 7 days. RESULTS: Glutamine
      significantly reduced gross damage and histopathological scores and prevented the
      decrease of anal pressure and the elevated myeloperoxidase activity observed in
      the colon of animals receiving TNBS. TNBS administration induced a marked
      increase of vascular cell adhesion molecule (VCAM-1), inducible nitric oxide
      synthase (iNOS), and cyclooxygenase-2 (COX-2) protein levels. These inflammatory
      events were associated with increased protein level of NF-kappaB p50 and p65
      subunits in the nucleus and significant phosphorylation/degradation of the
      inhibitor IkappaBalpha. Protein levels of the phosphorylated forms of STAT1,
      STAT5, and Akt were elevated in animals with colonic damage. All these effects
      were inhibited by administration of glutamine. Increases in the cytosolic
      concentration of TBARS and hydroperoxide-initiated chemiluminescence, markers of
      oxidative stress, and levels of tumor necrosis factor alpha (TNFalpha) and
      interferon gamma (IFNgamma) were significantly inhibited at 48 hours of TNBS
      instillation in glutamine-treated animals. CONCLUSIONS: Inhibition of the
      expression of proinflammatory mediators that are regulated by the NF-kappaB and
      STAT signaling pathways contribute to the therapeutical effect of glutamine in
      the TNBS model of experimental colitis. These effects may be brought about by
      inhibition of oxidative stress and reduced expression of proinflammatory
      cytokines.

PMID- 18623155
TI  - Stereotactic image-guided navigation in the preoperative imaging of perforators
      for DIEP flap breast reconstruction.
AB  - Preoperative imaging is sought prior to DIEA (Deep Inferior Epigastric Artery)
      perforator flaps due to the potential for maximizing operative success and
      minimizing operative complications. Recent advances include the use of computed
      tomography (CT) angiography (CTA) and magnetic resonance angiography. Image
      guided stereotactic surgery is a recent technique that has been used with success
      in several fields of surgery. The variability of perforator anatomy makes DIEA
      perforator flap surgery a suitable candidate for such technology, but as yet this
      has not been described. A study was undertaken to determine the feasibility of CT
      guided stereotaxy technique in DIEA perforator flap surgery and to compare
      findings with both conventional CTA and operative findings. Five consecutive
      patients planned for an elective DIEA perforator flap were recruited. Each
      patient underwent preoperative imaging of the anterior abdominal wall vasculature
      with both conventional CTA and CT-guided stereotactic imaging. Imaging findings
      were compared to operative findings. In all cases, all the major perforators were
      accurately localized with stereotactic imaging and with conventional CTA.
      Stereotactic navigation demonstrated a slightly better (nonsignificant)
      correlation with perforator location than conventional CTA. As such, CT-guided
      stereotactic imaging is an accurate method for the preoperative planning of DIEA
      perforator flaps, providing additional and potentially more accurate data to
      conventional CTA. With no additional scanning required, the method described in
      this paper allows the combined use of both methods for preoperative planning.

PMID- 18623156
TI  - Neural cell transplantation effects on sciatic nerve regeneration after a
      standardized crush injury in the rat.
AB  - The goal of the present study was to assess whether in vitro-differentiated N1E
      115 cells supported by a collagen membrane would enhance rat sciatic nerve
      regeneration after a crush injury. To set up an appropriate experimental model
      for investigating the effects of neural cell transplantation, we have recently
      described the sequence of functional and morphologic changes occurring after a
      standardized sciatic nerve crush injury with a nonserrated clamp. Functional
      recovery was evaluated using the sciatic functional index, the static sciatic
      index, the extensor postural thrust, the withdrawal reflex latency, and ankle
      kinematics. In addition, histomorphometric analysis was carried out on
      regenerated nerve fibers by means of the 2D-disector method. Based on the results
      of the EPT and of some of the ankle locomotor kinematic parameters analyzed, the
      hypothesis that N1E-115 cells may enhance nerve regeneration is partially
      supported although histomorphometry disclosed no significant difference in nerve
      fiber regeneration between the different experimental groups. Therefore, results
      suggest that enrichment of equine type III collagen membrane with the N1E-115
      cellular system in the rat sciatic nerve crush model may support recovery, at
      least in terms of motor function. The discrepancy between functional and
      morphological results also suggests that the combined use of functional and
      morphological analysis should be recommended for an overall assessment of
      recovery in nerve regeneration studies.

PMID- 18623157
TI  - In vitro and in vivo evaluation of a biodegradable chitosan-PLA composite
      peripheral nerve guide conduit material.
AB  - Chitosan, a nature biodegradable material, has good biocompatibility but poor
      physical properties to serve as a nerve conduit. In this study, polylactic acid
      (PLA) was added to chitosan to form a composite material with improved intensity
      and elasticity, to be used as nerve conduits. The chitosan-PLA nerve conduits
      were fabricated with a mold casting/infrared dehydration technique. The
      constituent ratio of PLA and chitosan of 1:5 (v:v) was chosen to give the
      composite material both good mechanical properties and good biocompatibility. An
      in vitro cytotoxicity test showed that the chitosan-PLA material was not
      cytotoxic. The conduits were proved biodegradable and had many micropores to
      allow permeability. We evaluated chitosan-PLA nerve conduits as a guidance
      channel to repair 10 mm gaps in rat sciatic nerves. Nerve autograft and silicon
      conduits were used as the control. After 12 weeks, the regenerating nerves in
      three groups succeeded in passing through the nerve gap and reinnervating the
      muscle. Assessments, including ECG, histomorphometric evaluation, and weighing of
      triceps calf muscle, showed that the functional recovery of sciatic nerve was
      better in chitosan-PLA conduit group than in the silicon conduit group (P <
      0.05), but the differences between the chitosan-PLA conduit group and the nerve
      autograft group were not significant (P > 0.05). Therefore, the chitosan-PLA
      guide proved to be a promising nerve conduit.

PMID- 18623158
TI  - Reconstruction of reflex pathways to the atonic bladder after conus medullaris
      injury: preliminary clinical results.
AB  - Neurogenic bladder dysfunction following spinal cord injury is a major medical
      and social problem for which there is no ideal treatment strategy. In this study,
      spinal root anastomoses were performed in 10 paraplegic patients with traumatic
      lesions of the conus medullaris, in an attempt to reinnervate the paralyzed
      bladder. For the operation, the functional T11 ventral root (VR) above the lesion
      was transected and anastomosed to the S2 ventral roots unilaterally through a
      nerve graft. The T11 dorsal root was left intact as the trigger for micturition
      after axonal regeneration. All patients underwent urodynamic evaluation before
      surgery and at follow-up. The mean follow-up duration was 2 years. Of the 10
      patients, 7 (70%) regained satisfactory bladder control within 18-24 months after
      VR microanastomosis. In these seven patients, the average bladder capacity
      decreased from 508 +/- 83 (mean +/- SD) to 370 +/- 59 ml, residual urine
      decreased from 477 +/- 98 to 35 +/- 11 ml, and urinary infections were not
      observed. Patients with impaired renal function experienced a full recovery.
      Three patients failed to show any improvement after the operation. These results
      suggest that a restitutive process occurs in the bladder following reinnervation
      from new T11 VR connections to the bladder nerves. Spinal cord lesions that may
      benefit from such a nerve crossover surgery are those located at the conus,
      whereby a functional suprasacral nerve can be connected to the sacral roots to
      bypass the injury in an attempt to restore central connections to the bladder.

PMID- 18623159
TI  - Secondary nerve reconstruction using vein conduit grafts for neglected digital
      nerve injuries.
AB  - Digital nerve defects can result from neglected nerve injuries. The standard
      method of reconstruction is nerve grafting, but donor-site morbidity encourages
      searching for alternative graft materials, including vein conduit grafts. From
      1995-2005, three patients with neglected digital nerve injuries received vein
      conduit grafting for digital nerve reconstruction in our hospital. The interval
      between the injury and the reconstructive procedure ranged from 17 days to 2
      years, and the length of the defects ranged from 0.8 to 2.5 cm. All the vein
      grafts were harvested from the distal forearm. Patient 1 had a moving and a
      static two-point discrimination (M2PD and S2PD) of 3 and 4 mm, respectively, at a
      12-year follow-up. Patient 2 had an M2PD of 5 mm and S2PD of 6 mm at an 11-year
      follow-up, and the patient 3 had both an M2PD and S2PD of 4 mm at a near 3-year
      follow-up. They all achieved useful sensory function (S3 and S3+) by modified
      Highet and Sander criteria. Although previous studies showed secondary repair
      using vein grafts yielded worse sensory recovery than that of primary repair, in
      our cases, secondary digital nerve reconstruction with vein conduit grafts gives
      excellent results at the long-term sensory evaluation, two of them with more than
      10 years' follow-up. To the best of our knowledge, this might be the longest
      follow-up after secondary digital nerve reconstruction using a vein conduit
      graft. It bears the advantages of readily accessible, no donor-site morbidity,
      and compatible in size with digital nerves.

PMID- 18623160
TI  - Use of the venous flap for salvage of difficult ring avulsion injuries.
AB  - Ring avulsion can lead to soft tissue compromise resulting in eventual digit
      failure or restriction of motion. The authors present use of the venous flow
      through flap for simultaneous soft tissue and digital vessel reconstruction in
      severe ring avulsion injury. A retrospective review of ring avulsion injuries
      treated with transplantation of an arterialized (A-V-A) venous flap between 1999
      and 2006 was conducted. Indications included digits which were debrided and
      required soft tissue and digital artery reconstruction. Eight venous flaps were
      transplanted for 3 Urbaniak class II and 5 Urbaniak class III ring avulsions.
      Average size of the venous flap was 6 cm(2). All flaps and digits survived
      without partial necrosis. The soft tissue envelope was supple in all cases. Total
      active motion (TAM) ranged from 160 to 210 degrees. The arterialized venous flow
      through flap is a reliable solution for the complex ring avulsion injury which
      requires simultaneous soft tissue and digital vessel reconstruction.

PMID- 18623161
TI  - A critical evaluation of the concomitant use of the implantable Doppler probe and
      the Vacuum Assisted Closure system in free tissue transfer.
AB  - Introduction of the Vacuum-Assisted Closure (V.A.C.) system has revolutionized
      the approach to a multitude of clinical settings. Yet, its use precludes adequate
      clinical monitoring of skin-grafted free flaps, thus, making a reliable
      monitoring system essential if broad clinical application is aspired. In a
      clinical study, the usefulness of the combination of the V.A.C. and implantable
      Doppler probe was critically evaluated in patients with microsurgical lower
      extremity reconstruction. We retrospectively analyzed the usefulness of the
      implantable Doppler probe in five consecutive patients treated in our department
      from January to July 2007. Inclusion criteria were lower extremity reconstruction
      by means of skin-grafted free tissue transfers with subsequent application of the
      V.A.C. device. Five consecutive patients (four males, one female) with a mean age
      of 37.8 years (range, 8-58 years) matched the criteria mentioned above. Of note,
      the two pediatric patients (8-year-old male and 12-year-old female) suffered from
      significant posttraumatic stress disorder necessitating concomitant psychological
      care by the Department of Psychiatry. All flaps healed uneventfully displaying no
      signs of vascular compromise. Interpretation of the Doppler signal was simple and
      well received by the nursing staff. The combination of V.A.C. and the implantable
      Doppler probe enhances patient comfort due to a reduction of the number of
      dressing changes while still allowing continuous free flap monitoring.
      Interpretation of the signal transmitted by the probe is simple and potentially
      reduces misinterpretations due to different levels of experience.

PMID- 18623162
TI  - Simple and reliable way in sternum wound coverage--tripedicle pectoralis major
      musculocutaneous flap.
AB  - OBJECTIVE: Sternotomy wound infection requires radically debridements and need
      secondary reconstruction of the resulting defect. Pectoralis major muscular or
      musculocutaneous flap is quite common in sternal wound closure. We modified the
      pectoralis major musculocutaneous flap design: bipedicle advancement cutaneous
      flap combined with thoracoacromial myocutaneous perforators, as a "tripedicle"
      fashion. We tried to utilize the cutaneous pedicle to provide a reliable skin
      coverage and decrease the wound dehiscence rate in lower one third sternal wound.
      METHODS: Four patients undergoing median sternotomy surgery between 2004 and 2007
      suffered from sternal wound infection and received tri-pedicle pectoralis major
      musculocutaneous flaps transfer. RESULTS: No skin paddle necrosis or wound
      dehiscence occurred in the postoperative course. Cosmetically and chest stability
      were satisfactory without complains about the daily activity. CONCLUSIONS:
      Tripedicle pectoralis major musculocutaneous flap is a simple and reliable
      technique to cover sternal wound defect necessitating resurfacing surgery. The
      blood supply to the skin paddle can be enriched by the superior and inferior
      cutaneous pedicle and the wound dehiscence rate is decreased with this technique.

PMID- 18623163
TI  - Extended left colon interposition for pharyngoesophageal reconstruction using
      distal-end arterial enhancement.
AB  - In pharyngoesophageal reconstruction with colon interposition, the oral segment
      of colon graft suffers from high incidence of ischemia necrosis. This leads to
      increased rate of fistula formation and hence increased mortality. This study
      described an arterial enhancement procedure for uncomplicated colon
      interposition. Five patients who had undergone pharyngoesophageal reconstruction
      with extended left colon interposition were reviewed, all of whom had advanced
      hypopharyngeal cancer with cervical esophagus invasion. Insufficient blood supply
      of the distal colon was noted following pharyngocolostomy. Arterial enhancement
      from the distal end of the sigmoid artery branch to the superior thyroid artery
      (four cases) or facial artery (one case) was performed. All patients displayed
      good circulation and peristalsis of colon interposition graft perioperatively.
      The pharyngocolostomy junction was free of leakage and colon graft necrosis.
      Barium study revealed a wide patent anastomosis postoperatively. Patients
      tolerated regular diet without problems following discharge. This demonstrated
      distal arterial enhancement procedure during extended colon interposition is a
      feasible technique for preventing serious complications for pharyngoesophageal
      reconstruction.

PMID- 18623164
TI  - Free DIEP and SIEA breast reconstruction to internal mammary intercostal
      perforating vessels with arterial microanastomosis using a mechanical coupling
      device.
AB  - Autologous breast reconstruction with microsurgical free tissue transfer has
      become routine, and perforator-based adipocutaneous flaps are recognized as an
      excellent option for many patients. Current efforts to optimize patient outcomes
      focus on minimizing operative morbidity both at the donor and recipient sites.
      The DIEAP flap avoids most of the abdominal wall morbidity associated with the
      TRAM. At the recipient site, however, partial rib resection, for access to the
      internal mammary (IM) artery and vein as recipient vessels, has a risk of chest
      wall pain, deformity, and pneumothorax. Perhaps more importantly, sacrifice of
      the IM vessels precludes their use for potential future coronary
      revascularization. To avoid this, the intercostal perforating branches from the
      internal mammary system may be used as recipient vessels for microanastomosis.
      This has been well described using suture technique, although the use of a
      mechanical coupling device for arterial anastomosis to the perforator has not
      been reported. We report nine cases whereby a mechanical coupling device was used
      to perform both the arterial and venous anastomoses of DIEAP and SIEA flap
      pedicles to IM intercostal perforating vessels. Flap ischemia time was shorter in
      all cases, allowed ease of anastomosis for vessel size mismatch, and is
      technically easier in deep wounds. This technique is a further refinement to free
      flap breast reconstruction and is a powerful application of the coupling device.

PMID- 18623165
TI  - Long-term health outcomes in pediatric inflammatory bowel disease: a population
      based study.
AB  - BACKGROUND: The long-term sequelae of inflammatory bowel disease (IBD) may differ
      between children and adults. We evaluated the health status of patients with
      pediatric onset of IBD and controls in early adulthood. METHODS: A questionnaire
      on the current health status and disease history was mailed to patients with
      childhood onset IBD diagnosed during 1987-2003 in 2 university hospitals in
      Finland. Matched controls were randomly selected from the Population Register
      Centre. RESULTS: A total of 368 (67%) of the 550 patients and 646 (37%) controls
      responded (median age 20 years). Ulcerative colitis (UC) was the most common
      primary diagnosis (58%) reclassified as Crohn's disease (CD) in 8.5%. Of the
      patients, 80% had been on glucocorticoids at some point (median duration of the
      disease 8.3 years). One-third of CD patients had undergone intestinal resection.
      In UC, total colectomy was common (24%). The frequency of joint diseases (5.4%
      versus 0.2%) and biliary duct diseases (2.7% versus 0.3%) was higher in patients
      than in controls (P < 0.001). Overall quality of life was decreased in the
      patients (mean score 5.7 versus 6.0 in controls, P < 0.001). Further, some
      impediment on adult height and weight was observed among male patients.
      CONCLUSIONS: IBD in children may have a more aggressive disease course than in
      adults, since most pediatric patients need glucocorticoids, and abdominal surgery
      is frequent. At 8 years from diagnosis, most patients have active disease and
      quality of life is slightly lower than in the rest of the population.

PMID- 18623166
TI  - Body mass and composition affect bone density in recently diagnosed inflammatory
      bowel disease: the Manitoba IBD Cohort Study.
AB  - BACKGROUND: This prospective study was undertaken to clarify the role of body
      mass and composition as a determinant of bone mineral density (BMD) in recently
      diagnosed inflammatory bowel disease (IBD). METHODS: A nested subgroup of 101
      adult subjects of the population-based Manitoba IBD Cohort Study were enrolled.
      Baseline BMD and body composition were measured and repeated 2.3 +/- 0.3 years
      later. RESULTS: Greater weight, height, and body mass measurements were
      positively correlated with bone density at all sites (P < 0.01). Although both
      fat tissue and lean tissue showed positive relationships with BMD, lean tissue
      showed a much stronger correlation than fat tissue, especially for the total hip
      (r = 0.66, P < 0.001 versus r = 0.23, P < 0.05) and total body measurements (r =
      0.59, P < 0.001 versus r = 0.04, P NS). Increase (or decrease) in hip bone
      density was strongly associated with an increase (or decrease) in all body mass
      variables (r = 0.49-0.54, P < 0.001). CONCLUSIONS: Measures of body mass are
      important determinants of baseline BMD in recently diagnosed IBD patients.
      Furthermore, change in body mass is correlated with change in BMD, especially at
      the total hip. Early optimization and maintenance of nutrition and body weight,
      particularly toward lean tissue mass, may play an important role in preventing
      IBD-related bone disease.

PMID- 18623167
TI  - Intestinal barrier dysfunction in inflammatory bowel diseases.
AB  - The etiology of human inflammatory bowel diseases (IBDs) is believed to involve
      inappropriate host responses to the complex commensal microbial flora in the gut,
      although an altered commensal flora is not completely excluded. A multifunctional
      cellular and secreted barrier separates the microbial flora from host tissues.
      Altered function of this barrier remains a major largely unexplored pathway to
      IBD. Although there is evidence of barrier dysfunction in IBD, it remains unclear
      whether this is a primary contributor to disease or a consequence of mucosal
      inflammation. Recent evidence from animal models demonstrating that genetic
      defects restricted to the epithelium can initiate intestinal inflammation in the
      presence of normal underlying immunity has refocused attention on epithelial
      dysfunction in IBD. We review the components of the secreted and cellular
      barrier, their regulation, including interactions with underlying innate and
      adaptive immunity, evidence from animal models of the barrier's role in
      preventing intestinal inflammation, and evidence of barrier dysfunction in both
      Crohn's disease and ulcerative colitis.

PMID- 18623168
TI  - Observer variability in the histologic diagnosis of microscopic colitis.
AB  - BACKGROUND: Microscopic colitis is diagnosed based on histologic criteria. There
      has been no investigation of the reproducibility of the histologic diagnosis of
      microscopic colitis. Our aim was to evaluate interobserver and intraobserver
      variation in this diagnosis. METHODS: Colonic biopsies from 90 subjects (20
      lymphocytic colitis, 20 collagenous colitis, 20 inflammatory bowel disease, and
      30 normal) were blindly and independently reviewed by 4 gastrointestinal
      pathologists. The biopsies were classified by each pathologist into 1 of 6
      diagnostic categories: lymphocytic colitis, collagenous colitis, active chronic
      colitis, focal active colitis, normal, or other. The slides were then relabeled
      and blindly reinterpreted 3 months later. The degree of agreement was determined
      using kappa statistics (lambda). RESULTS: Interobserver agreement with the 6
      diagnostic categories was 69% (kappa = 0.76, 95% CI 0.69, 0.83) and 70% (kappa =
      0.71, 95% CI 0.61, 0.79) for the first and second observations, respectively.
      Interobserver agreement with final diagnostic categories of microscopic colitis
      versus nonmicroscopic colitis was 91% (kappa = 0.90, 95% CI 0.82, 0.96) and 88%
      (kappa = 0.83, 95% CI 0.73, 0.92), respectively. Mean intraobserver agreement
      with the 6 diagnostic categories was 83% (kappa = 0.77). Mean intraobserver
      agreement with the final diagnostic categories of microscopic colitis versus
      nonmicroscopic colitis was 95% (kappa = 0.89). CONCLUSIONS: Both interobserver
      and intraobserver agreement were good in distinguishing among the 6 diagnostic
      categories, and excellent in distinguishing between microscopic colitis and
      nonmicroscopic colitis diagnoses. The histologic criteria for microscopic colitis
      provide for consistent and reproducible interindividual and intraindividual
      diagnoses in the evaluation of colonic biopsies.

PMID- 18623169
TI  - Subtype selective kainic acid receptor agonists: discovery and approaches to
      rational design.
AB  - (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian
      central nervous system, activating the plethora of glutamate receptors (GluRs).
      In broad lines, the GluRs are divided into two major classes: the ionotropic Glu
      receptors (iGluRs) and the metabotropic Glu receptors (mGluRs). Within the
      iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full
      agonist activity upon binding of the naturally occurring amino acid kainic acid
      (KA). Thus these receptors have been named the KA receptors. This review
      describes all-to our knowledge-published KA receptor agonists. In total, over 100
      compounds are described by means of chemical structure and available
      pharmacological data. With this perspective review, it is our intention to ignite
      and stimulate inspiration for future design and synthesis of novel subtype
      selective KA receptor agonists.

PMID- 18623170
TI  - Negative feedback regulation of colitogenic CD4+ T cells by increased
      granulopoiesis.
AB  - BACKGROUND: Chronic inflammatory diseases are characterized by massive
      infiltration of innate and acquired immune cells in inflammatory sites. However,
      it remains unclear how these cells cooperate in the development of disease.
      Although bone marrow (BM) is a primary site for hematopoiesis of immune cells
      except T cells, BM recruits memory T cells from the periphery. We have recently
      demonstrated that colitogenic CD4(+) memory T cells reside in BM of colitic
      CD4(+)CD45RB(high) T-cell-transferred SCID mice. Based on this background we here
      investigate whether granulocytes promote or suppress the expansion of colitogenic
      CD4(+) T cells. METHODS: First, we show that Gr-1(high)CD11b(+) granulocytes were
      significantly increased in colitic BM along with a significant increase of
      peripheral granulocytes. Consistently, the colony-forming unit (CFU) assay
      revealed that granulocyte colony formation was dominantly induced by supernatants
      from anti-CD3-stimulated colitic BM CD4(+) T cells. RESULTS: Administration of
      granulocyte-depleting anti-Gr-1 mAb to colitic mice did not ameliorate the
      colitis, but exacerbated the wasting disease with an increased expansion of
      systemic, but not lamina propria, CD4(+) T cells with activated phenotype.
      CONCLUSIONS: These results suggest that the increased granulopoiesis by
      colitogenic BM CD4(+) T cells represent a negative feedback mechanism to control
      systemic inflammation.

PMID- 18623171
TI  - Prevalence of penetrating disease and extraintestinal manifestations of Crohn's
      disease detected with CT enterography.
AB  - BACKGROUND: This study was conducted to determine the prevalence of penetrating
      disease and extraintestinal manifestations of Crohn's disease (CD) identified by
      computed tomography enterography (CTE). We also sought to examine the percentage
      of clinically significant new noninflammatory bowel disease (IBD) related
      findings in these patients. METHODS: We analyzed the records of 357 consecutive
      patients with previously diagnosed CD evaluated at our institution who underwent
      a CTE between August 2004 and October 2005. Radiology reports were reviewed for
      the presence of penetrating disease (abscess, fistula, or phlegmon) or
      extraintestinal IBD manifestations (nephrolithiasis, cholelithiasis,
      sacroiliitis, avascular necrosis, deep vein thrombosis, or primary sclerosing
      cholangitis). Additional non-IBD-related abnormalities were also recorded,
      including any mass or cystic lesion. Urgent findings were defined as those that
      were deemed by the radiologist or ordering physician to require medical follow-up
      within 3 months. RESULTS: Of 357 patients identified (51% female) the median age
      was 41.6 years and median disease duration was 9.9 years. Of this cohort, 20.7%
      had penetrating disease (new finding in 58.1%) and 18.8% had extraintestinal IBD
      manifestations (new finding in 67.2%). Six patients had primary sclerosing
      cholangitis and portal/mesenteric vein thrombosis, respectively. In addition,
      45.1% had non-IBD findings including 2 unsuspected malignancies. Most of these
      extraenteric non-IBD abnormalities were benign, with only 13.0% requiring urgent
      follow-up. CONCLUSIONS: CT enterography is a valuable diagnostic modality for
      detecting both penetrating disease and extraintestinal IBD manifestations. These
      data add to a growing body of evidence that supports the use of CTE in CD
      diagnostic and management algorithms.

PMID- 18623172
TI  - Nationwide patterns of hospitalizations to centers with high volume of admissions
      for inflammatory bowel disease and their impact on mortality.
AB  - BACKGROUND: We sought to determine patterns of hospitalizations for inflammatory
      bowel disease (IBD) to centers that regularly admit high volumes of IBD patients
      and whether they impacted health outcomes. METHODS: We queried US hospital
      discharges in the Nationwide Inpatient Sample to identify admissions with a
      primary diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between 1998
      and 2004. We determined patterns and predictors of hospitalization at high IBD
      volume admission centers (HIVACs) (>or=145 IBD admissions annually) and assessed
      their impact on mortality. RESULTS: Over 7 years the proportion of patients
      admitted to HIVACs increased from 2.3% to 14.8%. IBD patients were less likely to
      be admitted to an HIVAC if they were insured by Medicare (odds ratio [OR] 0.74;
      95% confidence interval [CI]: 0.65-0.83) or Medicaid (OR 0.71; 95% CI: 0.60
      0.84), or were uninsured (OR 0.42; 95% CI: 0.30-0.58) compared with those
      privately insured. Neighborhood income above the national median favored
      admission to an HIVAC (OR 1.99; 95% CI: 1.46-2.71). In-hospital mortality was
      lower among HIVACs compared to non-HIVACs (3.5/1000 versus 7.2/1000, P < 0.0001)
      and was persistent after adjustment for surgery status, age, comorbidity, and
      health insurance (OR 0.65; 95% CI: 0.49-0.87). When stratified by diagnosis,
      mortality was reduced at HIVACs among CD (OR 0.58; 95% CI: 0.37-0.90) but not UC
      admissions. CONCLUSIONS: There is a rising trend in hospitalizations for IBD at
      HIVACs, which confers mortality benefit for those with CD. Prospective studies
      are warranted to further explore the impact of these high-volume centers on IBD
      health outcomes.

PMID- 18623173
TI  - Mechanisms of probiotic action: Implications for therapeutic applications in
      inflammatory bowel diseases.
AB  - Probiotics are defined as nonpathogenic living microorganisms, including some
      commensal bacterial flora, which have beneficial effects on host health and
      disease prevention and/or treatment. Clinical trials have shown beneficial
      effects of probiotics on several human diseases, such as inflammatory bowel
      diseases (IBDs), which are among the most-studied diseases testing probiotics as
      a potential therapy. However, a significant question regarding clinical use of
      probiotics is the mechanism underlying the wide range of actions. Studies
      discussed in this review suggest 3 distinct cellular and molecular mechanisms for
      probiotic regulation in IBD therapy: 1) Probiotics block pathogenic bacterial
      effects by producing bactericidal substances and competing with pathogens and
      toxins for adherence to the intestinal epithelium; 2) Probiotics regulate immune
      responses by enhancing the innate immunity and modulating pathogen-induced
      inflammation via toll-like receptor-regulated signaling pathways; and 3)
      Probiotics regulate intestinal epithelial homeostasis by promoting intestinal
      epithelial cell survival, enhancing barrier function, and stimulating protective
      responses. Probiotics modulate host cell signaling pathways, including Akt,
      mitogen-activated protein kinases, and nuclear factor-kappaB to mediate these
      intestinal epithelial functions. It is hoped that developing a mechanistic
      understanding of probiotic action will provide the rationale to support the
      development of new hypothesis-driven studies to define the clinical efficacy in
      preventive, adjunctive, or alternative treatments for IBD.

PMID- 18623174
TI  - Use of the noninvasive components of the Mayo score to assess clinical response
      in ulcerative colitis.
AB  - BACKGROUND: The Mayo score and a noninvasive 9-point partial Mayo score are used
      as outcome measures for clinical trials assessing therapy for ulcerative colitis
      (UC). There are limited data assessing what defines a clinically relevant change
      in these indices. We sought to assess what constitutes a clinically meaningful
      change in these indices using data from a recently completed placebo-controlled
      clinical trial. METHODS: In all, 105 patients were enrolled in a 12-week
      randomized, placebo-controlled trial assessing rosiglitazone for treatment of
      mild to moderate UC. We compared the change in the Mayo score, the partial Mayo
      score, and a 6-point score composed just of the stool frequency and bleeding
      components of the Mayo score to the patient's perception of disease activity at
      week 0 and week 12. Optimal cutpoints were calculated as the maximal product of
      sensitivity and specificity. RESULTS: Each index was strongly correlated with the
      patient's rating of disease activity at week 12 (Spearman correlations 0.61-0.71,
      P < 0.0001 for all correlations). The maximal product of sensitivity and
      specificity to identify patient reported improvement of disease activity was
      achieved using cutpoints for change of 2.5 for the Mayo score (sensitivity 88%,
      specificity 80%), 2.5 for the partial Mayo score (sensitivity 88%, specificity
      87%), and 1.5 for the 6-point score (sensitivity 88%, specificity 80%).
      CONCLUSIONS: The partial Mayo score and the 6-point score composed solely of the
      stool frequency and bleeding components performed as well as the full Mayo score
      to identify patient perceived clinical response.

PMID- 18623175
TI  - Chronological changing patterns of clinical characteristics of Korean breast
      cancer patients during 10 years (1996-2006) using nationwide breast cancer
      registration on-line program: biannual update.
AB  - BACKGROUND: We performed this study to evaluate the chronological changes in
      Korean breast cancer characteristics and reproductive factors from 1996 to 2006.
      MATERIALS AND METHODS: We analyzed the chronological changes among newly
      diagnosed primary breast cancer patients recruited at 102 general hospitals. All
      participating hospitals provided the essential information through the nationwide
      on-line registration program. RESULTS: Eleven thousand two hundred seventy five
      cases of breast cancer were newly diagnosed in 2006. The crude incidence rate of
      breast cancer of 2006 was 46 (average 47.0 +/- 10.8) among 100,000 and the
      patient's median age was 48 (average 49.2 +/- 10.4) years (P < 0.001). In a
      difference from the United States and Western countries, the age distribution of
      breast cancer peaked in the fifth decade of life; this was followed by the sixth,
      fourth, and seventh decades. Compared with the results of previous studies 1996,
      this study also showed a continuous increase in: the incidence; breast-conserving
      surgery; breast reconstruction after operation; the percentage of early breast
      cancer; and the number of patients with risk factors. CONCLUSION: Our results
      suggest the incidence of breast cancer in Korea will continue to rise. Several
      characteristics of Korean breast cancer patients seem to follow the patterns of
      Western countries, but differences are present.

PMID- 18623176
TI  - Azathioprine-induced Sweet's syndrome in Crohn's disease.

PMID- 18623178
TI  - Optimizing environmental scanning electron microscopy of spheroidal reaggregated
      neuronal cultures.
AB  - Electrophysiological recordings from hen embryo brain spheroidal reaggregates on
      penetrating 3D multielectrode arrays could be understood more easily if the
      surface structure was known in more detail. Electrophysiological activity, as
      grouped spikes in trains, is acquired from spheroids, indicating the inner
      formation a neuronal network. To this end, spheroids can be observed by
      environmental scanning electron microscopy. Live spheroids collapse when the
      supporting water is evaporated. By careful adjustment of the chamber pressure it
      is possible to observe fully hydrated fixed spheroids. A thin film of water tends
      to prevent a clear view of the surface detail. This can be evaporated to reveal
      the surface while taking steps to avoid both inadvertent shrinkage and rewetting.
      Conventional SEM shows a very different surface that is rich in protruding cell
      bodies and fibers. The images are compared and interpreted with some images of
      the surface using transmission electron microscopy.

PMID- 18623177
TI  - The spatial distribution of glutamatergic inputs to dendrites of retinal ganglion
      cells.
AB  - The spatial pattern of excitatory glutamatergic input was visualized in a large
      series of ganglion cells of the rabbit retina, by using particle-mediated gene
      transfer of an expression plasmid for postsynaptic density 95-green fluorescent
      protein (PSD95-GFP). PSD95-GFP was confirmed as a marker of excitatory input by
      co-localization with synaptic ribbons (RIBEYE and kinesin II) and glutamate
      receptor subunits. Despite wide variation in the size, morphology, and functional
      complexity of the cells, the distribution of excitatory synaptic inputs followed
      a single set of rules: 1) the linear density of synaptic inputs (PSD95
      sites/linear mum) varied surprisingly little and showed little specialization
      within the arbor; 2) the total density of excitatory inputs across individual
      arbors peaked in a ring-shaped region surrounding the soma, which is in accord
      with high-resolution maps of receptive field sensitivity in the rabbit; and 3)
      the areal density scaled inversely with the total area of the dendritic arbor, so
      that narrow dendritic arbors receive more synapses per unit area than large ones.
      To achieve sensitivity comparable to that of large cells, those that report upon
      a small region of visual space may need to receive a denser synaptic input from
      within that space.

PMID- 18623179
TI  - Assembling and imaging of his-tag green fluorescent protein on mica surfaces
      studied by atomic force microscopy and fluorescence microscopy.
AB  - The adsorption of his-tag green fluorescent protein (GFPH(6)) onto the mica
      surfaces has been studied by atomic force microscopy (AFM) and laser confocal
      fluorescence microscopy. By controlling the adsorption conditions, separated
      single GFPH(6) and GFPH(6) monolayer can be adsorbed and formed on mica surfaces.
      In present experiments, based on the AFM measurement, we found that the adsorbed
      GFPH(6) was bound on the mica surface with its beta-sheets. The formed GFPH(6)
      monolayer on mica surfaces was flat, uniform, and stable. Some applications of
      the formed monolayer have been demonstrated. The formed monolayer can be used as
      a substrate for DNA imaging and AFM mechanical lithography.

PMID- 18623181
TI  - Microbial production of (+)-trans-isochorismic acid.
AB  - Two methods are described for the preparation of enantiomerically pure (+)-trans
      isochorismic acid, an important metabolite of the postchorismate pathway. Both
      methods can be employed to prepare isotopically labeled isochorismic acid. One of
      the two methods is suitable to prepare bulk quantities of isochorismic acid using
      a recombinant strain of Klebsiella pneumoniae 62-1. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623182
TI  - Intracellular flux analysis in hybridomas using mass balances and in vitro (13)C
      nmr.
AB  - Intracellular fluxes are important in defining cellular physiology and its
      changes in response to environmental variations. Stoichiometric balances combined
      with extra cellular metabolite measurements were applied to the estimation of
      intracellular fluxes and the study of energy metabolism in the hybridoma cell
      line ATCC CRL 1606. Redundant measurements allowed the evaluation of the
      consistency of the stoichiometry, measurements, and pseudo-steady-state
      assumption leading to refinement of the assumed biochemistry and identification
      of measurement errors. To validate the flux estimates, two batch experiments were
      performed with glucose labeled in the 1 position with (13)C. The distribution of
      (13)C in secreted lactate was measured via nuclear magnetic resonance
      spectroscopy (NMR) and compared to that predicted from the estimated
      intracellular fluxes. There was good agreement between the measured and estimated
      isotope distributions, demonstrating the validity of the flux estimates obtained
      from stoichiometric balances. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623183
TI  - Removal of phenols and aromatic amines from wastewater by a combination treatment
      with tyrosinase and a coagulant.
AB  - Removal of phenols and aromatic amines from industrial wastewater by tyrosinase
      was investigated. A color change from colorless to darkbrown was observed, but no
      precipitate was formed. Colored products were found to be easily removed by a
      combination treatment with tyrosinase and a cationic polymer coagulant containing
      amino group, such as hexamethylenediamine-epichlorohidrin polycondensate,
      polyethleneimine, or chitosan. The first two coagulants, synthetic polymers, were
      more effective than chitosan, a polymer produced in crustacean shells. Phenols
      and aromatic amines are not precipitated by any kind of coagulants, but their
      enzymatic reaction products are easily precipitated by a cationic polymer
      coagulant. These results indicate that the combination of tyrosinase and a
      cationic polymer coagulant is effective in removing carcinogenic phenols and
      aromatic amines from an aqueous solution. Immobilization of tyrosinase on
      magnetite gave a good retention of activity (80%) and storage stability i.e.,
      only 5% loss after 15 days of storage at ambient temperature. In the treatment of
      immobilized tyrosinase, colored enzymatic reaction products were removed by less
      coagulant compared with soluble tyrosinase. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623184
TI  - Development of optimized transfectoma cell lines for production of chimeric
      antibodies in hollow fiber cell culture systems.
AB  - Methods for the selection of transfectoma cells that express large quantities of
      mouse-human chimeric antibodies have been develped. SP2/0 mouse myeloma cells
      were transfected with pSV2-gpt and pSV2-neo based immunoglobulin expression
      vectors. Double transfectants were selected using the xanthine-guanine
      phosphoribosyl transferase (gpt)and the neomycin (neo) selection marker genes.
      ELISA-based screening of transfectoma clones resulted in the isolation of IgG
      producing transfectomas. Introduction of the kappa light-chain 3'-enhancer into
      the light-chain expression vector significantly increased immunoglobulin
      expression, but only when the enhancer was located at its physiological site, 9
      kb downstream of the kappa constant region exon. With some of the transfectomas,
      final yields of up to 80 mg/L of chimeric IgG were obtained in conventional flask
      cultures using serum-free growth medium. A pilot-scale AcuSyst Maximizer hollow
      fiber cell culture system was used for the production of gram amounts of chimeric
      IgG. Results obtained with different transfectoma clones in conventional culture
      were not fully predictive for yields in the hollow fiber system. In contrast,
      differences in productivity between individual clones in the laboratory-scale
      Tecnomouse cell culture unit were comparable with those in the Maximizer system.
      Up to 200 mg of chimeric IgG were produced per day in one Maximizer bioreactor.
      (c) 1995 John Wiley & Sons, Inc.

PMID- 18623185
TI  - Operational patterns affecting lactic acid production in ultrafiltration cell
      recycle bioreactor.
AB  - Lactic acid production with cell recycling on an ultrafiltration tubular membrane
      reactor was studied; higher lactic acid concentrations as well as productivities
      were obtained under long-term fermentations compared with other high cell density
      systems. Different operational conditions, namely dilution rates and start-up
      modes, were assessed. Performances were very different at the three different
      dilution rates tested (D = 0.20 h(-1), D = 0.40 h(-1), or D = 0.58 h(-1)). The
      different behaviours are discussed and factors responsible for them are
      presented. The best way to operate for lactic acid production is chosen, the
      dilution rate of D = 0.40 h(-1) being the one providing the best overall
      performance. On the other hand, results show that of the two start-up modes
      tested, continuous start (membrane open) permits higher permeabilities throughout
      the operational runs than batch start (membrane closed). Operational stability
      was found to be directly associated with membranes that work at "steady state,"
      the membrane permeability being kept around 15 L/m(2) h. Optimized cell bleed can
      improve time of operation if such membrane permeability can be maintained for a
      longer time. A comparison of results with those obtained in other lactic acid
      production systems is presented; such comparison shows that this tubular
      ultrafiltration membrane cell recycle reactor presents three important
      advantages: (1) concomitant lactic acid concentrations and productivities; (2)
      long periods of operation at reasonable permeabilities; and (3) good mechanical
      stability permitting the use of steam sterilization. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623186
TI  - Evaluation of cellulase recycling strategies for the hydrolysis of
      lignocellulosic substrates.
AB  - Recycling of cellulases should lower the overall cost of lignocellulosiic
      bioconversion processes. In this study, three recycling strategies were evaluated
      to determine their efficiencies over five successive rounds of hydrolysis. The
      effect of lignin on recycling was examined by comparing water-washed, steam
      exploded birch (WB; 32% lignin) and WB which had been further extracted with
      alkali and peroxide (PB; 4% lignin). When the cellulases were recovered from the
      residual substrates after partial hydrolysis of both substrates, the recovered
      cellulase activity toward the mixture of fresh and residual substrates decreased
      after each recycling step. When the cellulases in the supernatants were also
      recycled, up to 20% more activity could be recovered. In both of these cases, the
      recovered activities did not correspond to the activities expected from the
      amount of cellulase protein recovered during recycling. The best recovery was
      obtained when the cellulases were recovered from both the residue and the
      supernatant after complete hydrolysis of the PB substrate. In this case, all of
      the originally added cellulase activity could be recovered for four consecutive
      hydrolysis rounds. However, when the same recycling strategy was carried out
      using the WB substrate, the recovered cellulase activity declined quickly with
      each recycling round. In all three of the recycling strategies, lower cellulase
      activities were recovered from the substrates with higher lignin contents. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623187
TI  - Dielectrophoretic separation of cells: Continuous separation.
AB  - Dielectrophoresis is the movement of particles in non-uniform alternating and
      direct current (AC, DC) electric fields. When nonuniform electric fields are
      created between microelectrodes, cells will redistribute themselves around the
      electrodes, the force holding the cells in place dependig on the local electric
      field and on the electrical properties of the cells themselves and the suspending
      medium. Steric drag forces produced by a gentle fluid flow in the chamber can be
      used to separate cells by selectively lifting cells from potential energy wells
      produced by the electric field. The technique is demonstrated in the batch
      separation of bacteria, yeast cells, and plant cells. Continuous separation and
      extraction of two cell types can be achieved by repeated reversing of the fluid
      flow direction in phase with the switching on and off of the applied voltage, and
      the efficacy of the technique is demonstrated for viable and nonviable (heat
      treated) yeast cells. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623188
TI  - Esterification reactions catalyzed by Chromobacterium viscosum lipase in CTAB
      based microemulsion systems.
AB  - Chromobacterium viscosum (CV) lipase solubilized in water-in-oil (w/o)
      microemulsions based on the cationic surfactant hexadecyltrimethylammonium
      bromide (CTAB) have been used for multigram-scale ester synthesis, including the
      kinetic resolution of a secondary alcohol. The stability of CV lipase in all the
      CTAB microemulsions studied was excellent and was superior to that observed in
      aqueous buffer at the same pH and temperature. Kinetic studies were performed
      using the synthesis of ethylhexadecanoate as a model reaction. Under pseudo-first
      order conditions, the synthesis rates were linearlydependent on the enzyme and
      fatty acid concentrations and the R dependence shows the characteristic bell
      shaped curve (where R = [H(2)O]/[surfactant]). The dependence of enzyme activity
      toward octyldecanoate synthesis on the pH of the dispersed buffer phase is in
      marked contrast to that observed for the pH dependence of CV lipase toward p
      nitrophenylbutyrate hydrolysis. In the former case, the pH-activity profile is
      approximately sigmoidal, which may reflect the ionization state of the fatty acid
      substrate. In the latter case, the pH dependence is minimal at both R = 10 and R
      = 50, suggesting the enzyme does not experience a changed pH environment.
      Inclusion of a pH-sensitive probe molecule into those incubations containing
      fatty acid clearly demonstrates that the probe molecule experiences a changed
      environment consistent with that expected for the selected buffer. An in situ
      Fourier transform nuclear magnetic resonance (FT-NMR) assay has been developed
      which allows continuous monitoring of the esterification reactions, thereby
      providing an additional means of determining initial rates. The method may be of
      general value for lipase assays in microemulsions since it may provide, at the
      same time, information regarding enzyme regioselectivity. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623189
TI  - Kinetics of ethanol production by recombinant Escherichia coli KO11.
AB  - The fermentation kinetics for separate as well as simultaneous glucose and xylose
      fermentation with recombinant ethanologenic Escherichia coli KO11 are presented.
      Glucose and xylose were consumed simultaneously and exhibited mutual inhibition.
      The glucose exhibited 15 times stronger inhibition in xyclose fermentation than
      vice versa. The fermentation of condensate from steampretreated willow (Salix)
      was investigated. The kinetics were studied in detoxified as well as in
      nondetoxified condensate. The fermentation of the condensate followed two phases:
      First the glucose and some of the pentoses (xylose in addition to small amounts
      of arabinose) were fermented simultaneously, and then the remaining part of the
      pentoses were fermented. The rate of the first phase was independent of the
      detoxification method used, whereas the rate of the second phase was found to be
      strongly dependent. When the condensate was detoxified with overliming in
      combination with sulfite, which was the best detoxification method investigated,
      the sugars in the condensate, 9 g/L, were fermented in 11 h. The same
      fermentation took 150 h in nondetoxified condensate. The experimental data were
      used to develop an empirical model, describing the batch fermentation of
      recombinant E. coli KO11 in the condensate. The model is based on Monod kinetics
      including substrate and product inhibition and the sum of the inhibition exerted
      by the rest of the inhibitors, lumped together. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623190
TI  - Development of effective modified cellulase for cellulose hydrolysis process.
AB  - Cellulase was modified with amphilic copolymers made of alpha-allyl-omega-methoxy
      polyoxyalkylene (POA) and maleic acid anhydride (MAA) to improve the cellulose
      hydrolytic reactivity and cellulase separation. Amino groups of the cellulase
      molecule are covalently coupled with the MAA functional groups of the copolymer.
      At the maximum degree of modification (DM) of 55%, the modified cellulase
      activity retained more than 80% of the unmodified native cellulase activity. The
      modified cellulase shows greater stability against temperature, pH, and organic
      solvents, and demonstrated greater conversion of substrate than native cellulase
      does. Cellulase modification is also useful for controlling strong adsorption of
      cellulase onto substrate. Moreover, cellulase modified with the amphiphilic
      copolymer displays different separation characteristics which are new. One is a
      reactive two-phase partition and another is solubility in organic solvents. It
      appears that these characteristics of modified cellulase work very effectively in
      the hydrolysis of cellulose as a total system, which constitutes the purification
      of cellulase from culture broth, hydrolysis of cellulose, and recovery of
      cellulase from the reaction mixture. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623191
TI  - Preferential release of one daughter cell during division of immobilized chinese
      hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cells were attached to tiny adhesive sites in poly-2
      hydroxyethyl methacrylate(polyHEMA-) coated glass, and their divison properties
      were examined. The adhesive sites were produced by placing a metal mask,
      containing 8-mum-diameter holes arranged in a regular pattern, on top of the
      coated glass and exposing the sandwich to glow discharge treatment. This
      treatment produced an ordered array of circular cavities in the polyHEMA down to
      the glass. These adhesive sites were smaller in diameter than a newborn CHO cell,
      so that, upon division, there would theoretically be room for only one of the two
      new daughter cells to remain attached. It was found that individual CHO cells
      attached to, and grew upon, the sites, and that division normally resulted in the
      releas of one of the two new daughters. It is concluded that this culture
      technique has applications in research on the mammalian cell cycle, cell
      partitioning, and cellular senescence. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623192
TI  - In vivo quantification of acyclovir exposure in the dermis following
      iontophoresis of semisolid formulations.
AB  - The objective was to quantify acyclovir (ACV) exposure in the dermis following
      iontophoresis of nontraditional (pH-11 gels) and traditional (neutral cream)
      topical formulations of ACV. Given that the application time of a formulation on
      the skin can be significantly reduced with iontophoresis, the use of formulations
      optimized for iontophoretic delivery was explored to maximize the delivery of ACV
      to the site of action for the treatment of Herpes-labialis. Microdialysis probes
      were inserted into the shaved skin of tranquilized rabbits. Iontophoresis was
      performed at a constant current density of 200 microA/cm(2) for 60 min using a
      single-use drug cartridge filled with the following formulations: neutral cream,
      soluble fraction of the same cream (anodal and cathodal-current), or two
      formulations of pH-11 gels, one without and one with stabilizers and
      preservatives (cathodal-current). Results showed that only the ACV in the water
      phase of the cream is available for transport. All of the pH-11 gels exhibited a
      statistically significant (p < 0.001) increase in ACV dermis exposure compared to
      the neutral cream formulations without any additional sign of skin irritation. In
      conclusion, iontophoresis of ACV pH-11 gels provides higher ACV concentrations in
      the dermis than iontophoresis of neutral cream formulations, which could result
      in a better clinical outcome.

PMID- 18623193
TI  - A near-infrared spectroscopic investigation of relative density and crushing
      strength in four-component compacts.
AB  - Near-infrared spectroscopy (NIRS) is commonly employed for the analysis of
      chemical and physical attributes of intact pharmaceutical compacts. Specifically,
      NIRS has proven useful in the nondestructive measurement of tablet hardness or
      crushing strength. Near-infrared (NIR) reflectance and transmittance spectra were
      acquired for 174 13-mm compacts, which were produced according to a four
      constituent mixture design (29 points) composed of anhydrous theophylline,
      lactose monohydrate, microcrystalline cellulose, and soluble starch. Six compacts
      were produced for each design point by compacting at multiple pressures. Physical
      testing and regression analyses were used to model the effect of variation in
      relative density (and crushing strength) on NIR spectra. Chemometric analyses
      demonstrated that the overall spectral variance was strongly influenced by
      anhydrous theophylline as a result of the experimental design and the component's
      spectroscopic signature. The calibration for crushing strength was more linear
      than the relative density model, although accuracy was poorer in comparison to
      the density model due to imprecision of the reference measurements. Based on the
      consideration of reflectance and transmittance measurements, a revised
      rationalization for NIR sensitivity to compact hardness is presented.

PMID- 18623194
TI  - NMR search for polymorphic phase transformations in chlorpropamide form-A at high
      pressures.
AB  - The high-pressure effects on chlorpropamide (C10H13ClN2O3S) form-A have been
      studied by 1H NMR spectroscopy at high pressures up to 800 MPa in the temperature
      range 90-300 K. A study of the NMR second moment and spin-lattice relaxation time
      has been completed by a calculation of the steric hindrances for molecular
      reorientations and simulations of the second moment of the NMR line by the Monte
      Carlo method, which enabled a precise description of molecular dynamics in the
      compound studied. Reorientations of the methyl group, oscillations and
      reorientations of the chlorophenyl ring and reorientations of the propyl group
      have been revealed and respective activation parameters extracted. No phase
      transformation of the compound form-A has been detected.

PMID- 18623195
TI  - Rationale for combination use of targeted agents in ovarian cancer: do we have
      one?

PMID- 18623196
TI  - The morbidity and mortality of pediatric oncology patients presenting to the
      intensive care unit with septic shock.
AB  - BACKGROUND: Children with an underlying diagnosis of malignancy are at high risk
      for developing serious infections. Previous studies, although very limited in
      number, suggest a particularly poor outcome for these patients if admitted to an
      intensive care unit with septic shock. PROCEDURE: A review of all oncology
      patients admitted to the pediatric intensive care unit (PICU) at a tertiary care
      Children's Hospital over an 11-year period with a diagnosis of septic shock was
      performed. Patients were age and gender-matched with non-oncology patients also
      admitted to the PICU with septic shock during the same time period. Mortality and
      morbidity rates were compared, and risk factors for poor outcome were examined.
      RESULTS: The charts of 69 oncology patients and 69 control patients were
      reviewed. Mortality rate at PICU discharge was not significantly different
      between the two groups (15.9% in the oncology group, versus 11.6% in the control
      group, P = 0.607). Organ dysfunction was higher in the oncology group (P =
      0.005), although length of PICU stay was shorter (P = 0.036). There was no
      difference in ventilator days or vasopressor use. CONCLUSION: This review found
      that the survival of oncology patients admitted to the PICU with septic shock was
      not significantly different from control patients, and was significantly higher
      than previous reports. Aggressive management of these children is warranted as
      their long term prognosis may be much more favorable than originally thought.

PMID- 18623197
TI  - Improved growth velocity during thyroid hormone therapy in children with Fanconi
      anemia and borderline thyroid function.
AB  - BACKGROUND: Children with Fanconi anemia (FA) tend to have short stature, mild
      thyrotropin (TSH) elevation, and borderline low free thyroxine (FT4). Objective
      was to examine whether thyroid hormone therapy improves linear growth in children
      with FA and borderline thyroid function tests PROCEDURE: Thyroid function tests
      were performed in 63 children with FA. Eight subjects participated in a random
      order, double-blind, cross-over treatment for 7 months with levothyroxine and for
      7 months with placebo. Monitoring included growth measurements and laboratory
      assays at 1, 4 and 7 months of each phase. A 1 month lead in/wash out period was
      excluded from analysis of each treatment phase. RESULTS: The majority (63%) of FA
      children had borderline thyroid function tests. All eight FA subjects enrolled in
      the treatment study had FT4 in the lowest third of the normal range of 0.8-1.8
      ng/dL (10.3-23.2 pmol/L) [FT4 0.9 +/- 0.1 ng/dL (mean +/- SD), range 0.8-1.2
      ng/dL (10.3-15.4 pmol/L)]. TSH (optimal range 0.5-3 mU/L) was borderline elevated
      in six of eight subjects (4.0 +/- 1.5 mU/L, 1.9-7.3 mU/L). Growth velocity was
      slow at baseline and improved significantly during the thyroid phase compared to
      the placebo phase (2.1 +/- 1.2 cm/year vs. 5.4 +/- 1.7 cm/year, P < 0.05).
      CONCLUSIONS: Thyroid hormone therapy is safe and may improve linear growth
      velocity in children with FA who have borderline thyroid function. Subtle
      hypothyroidism has importance for growth in children. Whether thyroid hormone
      treatment improves adult height in these children remains to be elucidated.

PMID- 18623198
TI  - Children's views on their involvement in clinical research.

PMID- 18623199
TI  - Adolescents with cancer in developing countries: who offers the best care?

PMID- 18623200
TI  - A critical assessment of transcranial doppler screening rates in a large
      pediatric sickle cell center: opportunities to improve healthcare quality.
AB  - BACKGROUND: Transcranial Doppler ultrasound (TCD) has been demonstrated to be a
      powerful predictor of stroke risk due to sickle cell disease (SCD) in pediatric
      populations. Little is known about how this healthcare innovation has
      disseminated into preventive care for SCD. The objective of this study was to
      determine TCD screening rates and modifiable patient barriers in children with
      SCD. PROCEDURE: We retrospectively assessed the screening of 207 children with
      SCD at the Texas Children's Sickle Cell Center over a 3-year period (2004-2006).
      Demographics, adherence to comprehensive care visits, severity of disease, and
      distance from the sickle cell center were obtained from computerized medical
      record databases. Screenings cancelled or missed by patients were extracted from
      a computerized order entry system. RESULTS: The average yearly screening rate for
      eligible patients was 45%. The average yearly cancellation rate by patients was
      20%. Patient with private insurance were three times more likely to be compliant
      with ordered screenings than patients with Medicaid (P = 0.0077). Patients
      adherent to hematology comprehensive care visits more likely underwent ordered
      screenings than those who were not (P = 0.0386). When given at least one
      opportunity per year, providers, on average, ordered TCD screening 74% of the
      time when it was indicated. CONCLUSIONS: Despite evidence that routine screening
      to assess stroke risk is vital to the preventive care of SCD, implementation of
      this healthcare technology may be slow to disseminate due to patient and provider
      related factors.

PMID- 18623201
TI  - Compatibility of a protein topical gel with wound dressings.
AB  - The compatibility between several dressing materials and a recombinant human
      vascular endothelial growth factor (rhVEGF) topical methylcellulose gel
      formulation was investigated. The dressings being studied were Adaptic, Non-stick
      Dressing, Conformant 2, Opsite and Tegapore. The criteria to select a compatible
      dressing include protein stability, absence of leachables from the dressing, and
      ability to retain gel on wound. An LC-MS method with sample treatment using
      cellulase was developed to determine protein oxidation in gel formulations.
      Results showed that rhVEGF was significantly oxidized by Adaptic dressing in 24
      h. Protein oxidation was likely due to the peroxides, as determined by FOX assay,
      released into the protein solution from the dressing. Furthermore, Adaptic
      dressing caused protein adsorption loss, formation of high MW protein adducts,
      and released leachables as determined by RP-HPLC, LC-MS, and SEC. No protein
      oxidation or loss was observed after exposure to the other four alternative
      dressings. However, unknown leachables were detected in the presence of Opsite
      and Non-stick Dressing. The pore sizes of the Conformant 2 and Non-stick
      dressings were too large to hold the topical gel within the wound area, making
      them unsuitable for patient use. No rhVEGF bioactivity loss was observed in the
      presence of Tegapore. In conclusion, Tegapore was considered suitable for the
      rhVEGF topical gel.

PMID- 18623202
TI  - Congenital Ewing sarcoma in retroperitoneum with multiple metastases.
AB  - A 7-day-old Japanese female showed the absence of spontaneous movement in her
      both legs. MRI revealed tumors in the retroperitoneum invading into the spinal
      canal, the left cerebral hemisphere and the right eyeball. Histological
      examination of retroperitoneal tumor revealed the sheets of undifferentiated
      small round cells with hyperchromatic nuclei and scanty cytoplasm. EWS-FLI1
      fusion gene was detected by RT-PCR, indicating Ewing sarcoma. She received chemo
      radiotherapy and survived for 2 years and 10 months despite the multiple
      metastases at initial presentation.

PMID- 18623204
TI  - Forced degradation of betamethasone sodium phosphate under solid state:
      Formation, characterization, and mechanistic study of all four 17,20
      diastereomers of betamethasone 17-deoxy-20-hydroxy-21-oic acid.
AB  - Four diastereomers of betamethasone 17-deoxy-20-hydroxy-21-oic acid were found to
      be degradants of betamethasone sodium phosphate when the latter was stressed by
      heat under the solid state. The structure elucidation of these four diastereomers
      was achieved by a combination of LC-MS(n) (n = 1-3), various 1D and 2D NMR
      experiments, and mechanistic consideration of potential degradation pathways. A
      mechanism for the formation of the four degradants has been proposed, which
      involves hydration of a key intermediary degradant, betamethasone enol aldehyde,
      followed by intramolecular Cannizzaro reaction. The proposed mechanism is
      supported by a model reaction which converted betamethasone enol aldehyde into
      the four diastereomeric degradants in good yields, albeit in solution chemistry.

PMID- 18623205
TI  - Current practice perspectives on the management of thrombosis in children with
      renal insufficiency: the results of a survey of pediatric hematologists in North
      America.
AB  - BACKGROUND: No guidelines exist for the management of venous thromboembolic
      events (VTE) in children with renal insufficiency (RI). OBJECTIVE: To define
      current practice patterns of VTE management in children with RI. METHODS: An
      online multiple choice survey encompassing general questions/clinical scenarios
      related to thrombosis in RI. STUDY PARTICIPANTS: Pediatric hematologists who were
      members of Hemophilia and Thrombosis Research Society (HTRS) of North America.
      RESULTS: Response rate was 54% (39/75). VTE was perceived as the major hemostatic
      problem in children with RI by half (20/39) of respondents. All respondents used
      anticoagulation for treatment of VTE while 56% used it for prophylaxis of VTE in
      this population. Management practices varied with respect to choice of
      anticoagulants employed, consideration of prophylactic anticoagulation, and
      evaluation for hereditary thrombophilia. Low molecular weight heparin was
      perceived as a safe anticoagulation for VTE treatment by 77% of respondents given
      that anti-factor Xa monitoring was performed to assess bioaccumulation in RI.
      Thromboprophylaxis was considered for preventing thrombosis at central venous
      catheter, renal allo-graft and arterio-venous fistula in the context of previous
      history of thrombosis and congenital/acquired thrombophilia. The majority (>70%)
      would treat life-threatening emergencies such as superior vena cava syndrome with
      fibrinolytics despite RI. CONCLUSIONS: This pediatric study documents that
      substantial variability existed among pediatric hemologists with respect to VTE
      management in children with RI. Larger studies are required to better define the
      epidemiology and management of VTE in children with RI including the value of
      screening for underlying hereditary thrombophilia.

PMID- 18623203
TI  - Transdermal delivery of bupropion and its active metabolite, hydroxybupropion: a
      prodrug strategy as an alternative approach.
AB  - This investigation includes an evaluation of the percutaneous absorption of
      bupropion (BUP) and hydroxybupropion (BUPOH) in vitro and in vivo. In addition, a
      carbamate prodrug of BUPOH (But-BUPOH) was evaluated in vitro. In vitro diffusion
      studies were conducted in a flow-through diffusion cell system. The in vitro mean
      steady-state flux of BUP was significantly higher (p < 0.001) compared to BUPOH
      (320 +/- 16 nmol cm(-2) h(-1) vs. 27 +/- 4 nmol cm(-2) h(-1)). Additionally, a
      good correlation existed between in vitro and in vivo results. Mean steady-state
      plasma concentrations of 442 +/- 32 ng/mL and125 +/- 18 ng/mL were maintained
      over 48 h after topical application of BUP and BUPOH in hairless guinea pigs in
      vivo, respectively. Although BUP traversed human skin at rates sufficient to
      achieve required plasma levels, it is chemically unstable and hygroscopic, and
      unsuitable for transdermal formulation. On the other hand, BUPOH is stable but
      its transport across skin is much slower. Alternatively, the prodrug But-BUPOH
      was found to be stable, and also provided a 2.7-fold increase in the transdermal
      flux of BUPOH across human skin in vitro. Thus, But-BUPOH provides a viable
      option for the transdermal delivery of BUPOH.

PMID- 18623206
TI  - Dose intensive melphalan and cyclophosphamide with autologous hematopoietic stem
      cells for recurrent medulloblastoma or germinoma.
AB  - PURPOSE: To determine the response, toxicity, and survival for children with
      progressive or recurrent medulloblastoma and germinoma using a single
      myeloablative course of chemotherapy supported by autologous hematopoietic stem
      cells. PATIENTS AND METHODS: Subjects were in second remission or had minimal
      residual disease at the time of study entry. The conditioning regimen consisted
      of cyclophosphamide 6,000 mg/m(2) plus melphalan 180 mg/m(2). RESULTS: Twenty
      nine evaluable pediatric patients were accrued. The most frequent major
      toxicities were myelosuppression, infections, and stomatitis, but no toxic deaths
      were recorded. Best responses were: CR = 6, CCR = 13, PR = 6, SD = 2, and PD = 2.
      There were 6 medulloblastoma and 3 germinoma survivors with a median follow-up of
      7.5 years (range = 2.8-10). Two germinoma survivors received radiotherapy after
      autografting for presumptive progressive disease. CONCLUSION: Myeloablative
      chemotherapy consisting of cyclophosphamide and melphalan was tolerable in the
      relapsed brain tumor setting with 19/29 cases achieving CR or CCR status and 9/29
      becoming long-term survivors.

PMID- 18623207
TI  - Increased serum monocyte chemoattractant protein-1, macrophage inflammatory
      protein-1beta, and interleukin-8 concentrations in hemophagocytic
      lymphohistiocytosis.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is characterized by
      hypercytokinemia caused by macrophage and T cell activation. We analyzed the
      serum concentrations of monocyte chemoattractant protein (MCP)-1, macrophage
      inflammatory protein (MIP)-1beta, and interleukin (IL)-8 to investigate the roles
      of these chemokines in the pathophysiology of HLH. METHODS: Seven patients
      clinically diagnosed with HLH were examined. Serum cytokines and chemokines were
      measured. The differences in the serum concentrations between the patients with
      HLH and the controls were investigated. RESULTS: In patients with an active phase
      of HLH, the serum MCP-1, MIP-1beta, and IL-8 levels all were significantly higher
      than in healthy controls. The chemokine elevations decreased rapidly after
      initiation of chemotherapy. During increases in disease activity, elevation of
      MCP-1 and MIP-1beta preceded elevation of the serum ferritin level, which is a
      clinical indicator of HLH disease activity. CONCLUSIONS: These results suggest
      that MCP-1, MIP-1beta, and IL-8 play important roles in the pathophysiology of
      HLH. In addition, the serum concentrations of these chemokines may be sensitive
      markers for assessing disease activity in patients with HLH.

PMID- 18623208
TI  - A national approach to evaluating delays in diagnosis and treatment: potential
      implications for age related and geo-political differences in access to care and
      outcome in children and adolescents with cancer.

PMID- 18623210
TI  - Neuropsychological sequelae in patients with neurodegenerative Langerhans cell
      histiocytosis.
AB  - BACKGROUND: Patients with Langerhans cell histiocytosis (LCH) may develop
      neurodegeneration and significant CNS sequelae, affecting a significant
      proportion of the patients. We here aimed to investigate the neuropsychological
      consequences in more detail. METHODS: Using an extensive neuropsychological test
      battery, we evaluated nine LCH patients, 6-20 years old, with radiological signs
      indicative of neurodegeneration. RESULTS: Altogether 3/9 patients performed below
      1 SD of normal for age on full IQ. Detailed analysis revealed that 4/9 had
      deficient performance IQ, whereas 1/9 had subnormal verbal IQ (defined as below 1
      SD). Furthermore, 3/8 patients showed slow speed of performance for age. Notably,
      8/9 (89%) had deficient verbal working memory and 7/8 (88%) performed below
      normal on visual-spatial working memory. CONCLUSIONS: The results indicate a
      specific, uneven neuropsychological profile in patients affected by CNS-LCH, with
      a decline particularly on perceptual tasks whereas the verbal performance was not
      as negatively influenced. Furthermore, verbal and visual-spatial working memory
      functions were below normal for age in all but one patient studied. LCH may
      easily be misdiagnosed, but it is important that individuals affected by CNS-LCH
      are diagnosed to provide advice and support. It remains a challenge to find a
      treatment reducing this unfortunate neurodegeneration.

PMID- 18623211
TI  - Mixing properties of lyophilized protein systems: a spectroscopic and
      calorimetric study.
AB  - The purpose of this study was to investigate the solid-state properties of
      lyophilized formulations of protein (ribonuclease A) containing sucrose or
      trehalose across a wide range of compositions, both in the presence or absence of
      hydroxyethylstarch (HES). Infrared spectroscopy reveals that the protein forms
      hydrogen bonds to sugars (sucrose or trehalose) as water is removed from the
      sample. The strength and/or number of hydrogen bonds in dried samples increase as
      the weight fraction of sugar increases. Significant deviations of glass
      transition temperatures (T(g)'s) from those predicted by free volume theory are
      seen in both protein-sugar systems. The behavior can be explained by formation of
      protein-sugar hydrogen bonds at the expense of self-interactions between the
      sugars. Attractive interactions between lyophilized ribonuclease A and HES were
      detected spectroscopically and from thermodynamic analysis of T(g) values,
      contrary to the view that HES is sterically hindered from interacting with the
      protein surface. Sucrose-HES interactions were much less favorable than trehalose
      HES interactions, suggesting that phase separation in sugar/HES/protein mixtures
      would be more likely in the presence of sucrose than trehalose. Finally, the
      thermodynamics of mixing were investigated using differential scanning
      calorimetry (DSC) providing some of the first data for such solid protein sugar
      formulations with and without HES. In nearly all samples, positive excess
      enthalpy, excess entropy and excess free energy were observed, with the excess
      free energy being greater for samples containing sucrose rather than trehalose.
      Analysis of Flory-Huggins chi parameters suggests that phase separation between
      protein and excipients may be thermodynamically favored in these dried solid
      preparations.

PMID- 18623209
TI  - Effects of chemical enhancers on human epidermal membrane: Structure-enhancement
      relationship based on maximum enhancement (E(max)).
AB  - Chemical penetration enhancers are widely used in transdermal pharmaceuticals as
      well as cosmetic products. Selection of suitable enhancers in topical
      formulations requires an understanding of the mechanism of action of these
      enhancers. The objective of the present study was to evaluate the enhancement
      effects of a number of commonly known enhancers and cosmetic ingredients on
      permeation across human epidermal membrane (HEM). The potencies of these chemical
      enhancers-maximum enhancement, E(max)-were compared at their highest
      thermodynamic activity in equilibrium with HEM (i.e., solubility equilibrium).
      This was achieved by the treatment of HEM with the enhancer or phosphate buffered
      saline (PBS) saturated with the enhancer. Passive transport experiments were then
      conducted with a model permeant corticosterone to determine the effects of these
      enhancers on the lipoidal pathway of HEM. The results suggest that E(max) of an
      enhancer is related to its octanol/water partition coefficient and its solubility
      in the HEM lipid domain. A relationship between enhancer E(max) and its
      solubility in silicone elastomer was also observed, suggesting the use of
      silicone solubility to predict enhancer potency. Based on the E(max) results,
      some common topical ingredients were found to be more potent enhancers than a
      number of well-known chemical enhancers.

PMID- 18623212
TI  - Pancytopenia with myelodysplasia due to copper deficiency.
AB  - We present a case of pancytopenia in a 9-month-old infant with total parenteral
      nutrition (TPN) dependence due to short bowel syndrome. Bone marrow examination
      revealed left-shifted myeloid maturation, erythroid and myeloid dysplasia with
      normal iron stores. Serum copper level was 2 microm/dl (normal range 90-190
      mcg/dl). After supplementation, copper levels normalized at 143 mcg/dl, and the
      macrocytic anemia, neutropenia, and thrombocytopenia resolved. Copper deficiency
      should be considered in the differential diagnosis of cytopenias and
      myelodsyplasia, particularly in the growing number of pediatric patients with TPN
      dependency or malabsorption.

PMID- 18623213
TI  - Reversal of multidrug resistance by methoxypolyethylene glycol-block
      polycaprolactone diblock copolymers through the inhibition of P-glycoprotein
      function.
AB  - Overexpression of P-glycoprotein (Pgp) is one of the major limitations in cancer
      chemotherapy. Previous work has shown that amphiphilic diblock copolymers
      composed of methoxypolyethylene glycol-block-polycaprolactone (MePEG-b-PCL)
      diblock copolymers enhanced the cellular accumulation of Pgp substrates by
      modulating the function of this drug efflux transporter. The objective of this
      work was to determine whether MePEG-b-PCL diblock copolymers modulated Pgp
      function in multidrug resistant (MDR) cancer cells. The diblock copolymer
      enhanced the accumulation of various Pgp substrates in Pgp overexpressing MDR
      cells but did not influence substrate accumulation in non-Pgp expressing cells.
      Treatment of MDR cells with the diblock copolymer enhanced paclitaxel (ptx) and
      doxorubicin (dox) accumulation. Following uptake, ptx was rapidly effluxed from
      MDR cells whereas diblock copolymer treatment retained dox inside MDR cells.
      Treatment of MDR cells with the diblock copolymer reversed drug resistance to dox
      but not ptx. However, resistance to ptx was reversed by verapamil, which
      indicated that a sustained inhibition of Pgp was required for ptx to induce
      cytotoxicity in MDR cells. Taken together, these results highlight the potential
      of MePEG-b-PCL diblock copolymer to reverse drug resistance in MDR cancer cells
      through inhibition of Pgp function, making it a promising candidate for
      overcoming MDR.

PMID- 18623214
TI  - Congenital anomaly and childhood cancer: A population-based, record linkage
      study.
AB  - BACKGROUND: The cause of the majority of childhood malignancies is unknown.
      Association with the presence of congenital anomalies has been noted in some
      studies. In this study, we describe and quantify the association between
      congenital anomalies and childhood cancer. PROCEDURE: Cases from the Northern
      Congenital Abnormality Survey (NorCAS) and the Northern Region Young Persons
      Malignant Disease Registry (NRYPMDR) were matched using four key variables:
      surname at birth, date of birth, postcode at birth, and infant gender. All
      potential matches were checked manually. A second match was performed for
      children with matched birth dates, postcodes and gender but different surnames,
      to identify children whose surname at diagnosis was not the same as at birth.
      RESULTS: Thirty-nine children with a congenital anomaly and a diagnosis of cancer
      were identified from a cohort of 599,290 children born during 1985-2001. There
      was an almost threefold overall increased risk of malignancy among these children
      (RR = 2.9; 95% CI 2.1, 3.9), particularly of acute lymphoblastic leukaemia (RR =
      2.7; 95% CI 1.5, 5.0), acute myeloblastic leukaemia (RR = 22.0; 95% CI 12.1,
      40.0), other leukaemia (RR = 7.5; 95% CI 1.3, 43.6) and lymphomas (RR = 5.3; 95%
      CI 2.4, 12.0). This increased rate remained when children with Down syndrome were
      excluded (RR = 1.8, 95% CI 1.2, 2.7). CONCLUSION: Our findings suggest that
      children born with congenital anomalies are at increased risk of certain types of
      cancer. Further linkage studies between high quality registers, may provide
      insights into the origins of such malignancies.

PMID- 18623216
TI  - Comprehensive validation scheme for in situ fiber optics dissolution method for
      pharmaceutical drug product testing.
AB  - There has been a growing interest during the past decade in the use of fiber
      optics dissolution testing. Use of this novel technology is mainly confined to
      research and development laboratories. It has not yet emerged as a tool for end
      product release testing despite its ability to generate in situ results and
      efficiency improvement. One potential reason may be the lack of clear validation
      guidelines that can be applied for the assessment of suitability of fiber optics.
      This article describes a comprehensive validation scheme and development of a
      reliable, robust, reproducible and cost-effective dissolution test using fiber
      optics technology. The test was successfully applied for characterizing the
      dissolution behavior of a 40-mg immediate-release tablet dosage form that is
      under development at Novartis Pharmaceuticals, East Hanover, New Jersey. The
      method was validated for the following parameters: linearity, precision,
      accuracy, specificity, and robustness. In particular, robustness was evaluated in
      terms of probe sampling depth and probe orientation. The in situ fiber optic
      method was found to be comparable to the existing manual sampling dissolution
      method. Finally, the fiber optic dissolution test was successfully performed by
      different operators on different days, to further enhance the validity of the
      method. The results demonstrate that the fiber optics technology can be
      successfully validated for end product dissolution/release testing.

PMID- 18623215
TI  - Late effects in survivors of tandem peripheral blood stem cell transplant for
      high-risk neuroblastoma.
AB  - BACKGROUND: Increasing numbers of children with advanced neuroblastoma are
      achieving cure. We describe the clinical late effects specific to survivors of
      stage IV neuroblastoma all similarly treated using tandem autologous peripheral
      blood stem cell rescue with TBI. METHOD: The medical records of 35 neuroblastoma
      patients treated at CHOP between 1997 and 2001 were examined. Eighteen of the 35
      patients died of progressive disease, and 4 were lost to follow-up. Thirteen
      patients continue to follow-up in our Multidisciplinary Cancer Survivorship
      Clinic where they are evaluated and monitored by a consistent group of
      subspecialists that evaluate long-term sequelae. Data on treatment exposures
      including TBI and treatment related sequelae identified by clinician assessment
      and/or diagnostic testing were collected. RESULTS: Results indicate late effects
      were present in all 13 subjects, 12 of whom suffered from multiple negative
      sequelae, including issues with growth hormone deficiency, dental problems,
      osteochondromas and hearing deficiencies, among others, most at higher rates than
      reported previously. CONCLUSIONS: The findings in this small cohort indicate the
      need for future prospective studies of this intensive pediatric cancer treatment,
      and underscore the importance of medical intervention and long-term monitoring of
      these at-risk subjects to increase overall quality-of-life.

PMID- 18623217
TI  - Parental perceptions of being told their child has cancer.
AB  - BACKGROUND: Finding out that your child has cancer is a devastating experience.
      How this information is communicated can have a lasting impression on parents
      receiving the news. The purpose of this study was to assess how well parents
      recall discussing the diagnosis of cancer and to summarize suggestions for
      improvement. METHODS: A questionnaire was developed with input from several
      parents of children previously diagnosed with cancer. All parents of children <18
      years of age with a diagnosis of cancer who were >1 month post-diagnosis at our
      children's hospital were asked to participate. The patient sample was identified
      through the in- and outpatient clinics from June to August 2006. RESULTS: One
      hundred sixteen parents (mothers and fathers) completed the questionnaire, with
      only two parents refusing (1.7%). The moment of disclosure of the diagnosis was
      remembered vividly in 77%, well in 20%, and somewhat, vaguely or not at all in 1%
      each. Parental reaction to the disclosure was viewed as a positive experience 79%
      of the time and a negative experience 21% of the time. Parents also provided a
      number of suggestions for future disclosure. CONCLUSIONS: The majority of parents
      recall receiving the diagnosis and the discussions that ensued about their
      child's diagnosis of cancer. Most parents were satisfied with their experience
      with receiving the diagnosis. Suggestions for improvement can be incorporated
      into future educational indicatives for front line healthcare providers to
      improve communication of sensitive diagnoses with parents.

PMID- 18623218
TI  - Clofarabine in refractory Langerhans cell histiocytosis.
AB  - Patients with multi-system Langerhans cell histiocytosis (LCH) who progress on
      frontline therapy have a dismal outcome. Responses to cladribine have been
      reported in relapsed LCH, but there are no well defined salvage regimens for LCH
      is refractory to therapy. The next generation deoxyadenosine analog, clofarabine,
      has demonstrated activity in patients with leukemia that is refractory to salvage
      regimens, including other nucleotide congeners; however, no experience exist on
      the use of clofarabine in LCH. In this report we describe significant single
      agent activity of clofarabine in disseminated LCH refractory to salvage regimens,
      including cladribine.

PMID- 18623219
TI  - Mannosylated cationic liposomes/CpG DNA complex for the treatment of hepatic
      metastasis after intravenous administration in mice.
AB  - Immunotherapy using immunostimulatory CpG DNA could be a promising new
      therapeutic approach to combat refractory hepatic metastasis. In this study, we
      report the use of a conventional cationic liposomes/CpG DNA complex (Bare/CpG DNA
      lipoplex) and a mannosylated cationic liposomes/CpG DNA complex (Man/CpG DNA
      lipoplex) for effective inhibition of hepatic metastasis in mice. After
      intravenous administration of Bare/CpG DNA lipoplex, higher amounts of IL-12 and
      IFN-gamma were produced in serum or liver compared with naked CpG DNA, and their
      production was increased further by Man/CpG DNA lipoplex. Then, Bare/CpG DNA
      lipoplex and Man/CpG DNA lipoplex were administered intravenously to hepatic
      metastasis model mice, and the numbers of tumor cells (colon26/Luc) were
      quantitatively assayed. The number of tumor cells in Man/CpG DNA lipoplex-treated
      mice was same as those in Bare/CpG DNA lipoplex-treated mice. These results
      suggest that intravenous administration of not only Bare/CpG DNA lipoplex but
      also Man/CpG DNA lipoplex could be an efficient immunotherapy for hepatic
      metastasis.

PMID- 18623220
TI  - MRI abnormalities in infants with sickle cell anemia-indication for preemptive
      therapy?

PMID- 18623221
TI  - JAK2 V617F positive polycythemia Vera in a child with neurofibromatosis type I.
AB  - We report a child with polycythemia vera (PV). This patient demonstrates the
      acquired somatic JAK2 V617F mutation and also has neurofibromatosis type I (NF1).
      NF1, while not previously associated with PV, is associated with another
      childhood MPD, juvenile myelomonocytic leukemia (JMML). Thus we examined a number
      of genetic abnormalities identified in JMML patients, but found no association in
      this case. Neurofibromin sequencing failed to identify a causative mutation. An
      unknown genetic abnormality resulting in NF1 may have predisposed this young
      child to acquiring the common JAK2 mutation.

PMID- 18623222
TI  - Solvent effects on the AIBN forced degradation of cumene: Implications for forced
      degradation practices.
AB  - Solvent effects on the AIBN and ACVA forced degradation of cumene are explored.
      The degradant formation rates of the three cumene oxidative degradants, cumene
      hydroperoxide, acetophenone, and 2-phenyl-2-propanol are reported. The relative
      abundance and ratios of these three degradants provide insight into the fate of
      the peroxy radical oxidants generated by the forced stress system, and suggest
      that alkoxy radicals are actually a significant source of the observed
      reactivity. The presence of even 1% methanol in the forced stress solvent
      significantly quenches this alkoxy radical reactivity, dramatically reducing the
      overall degradation rate and leaving cumene hydroperoxide as the major product of
      the oxidation reaction. The origin of this significant solvent effect on the
      oxidation product distribution is shown to be related to the preferential H-atom
      abstraction from methanol and its trace impurities by any alkoxy radicals present
      in the reaction solution. The implications for these observations are explored
      with the intent of producing more predictive oxidative forced stress experiments.

PMID- 18623223
TI  - Myocardial iron overload in transfusion-dependent pediatric patients with acute
      leukemia.
AB  - For patients who regularly receive blood transfusions, cardiac failure is the
      major cause of death. This is most alarming because it progresses rapidly and is
      difficult to manage. We present three pediatric patients with acute leukemia
      whose therapy-induced anemia was treated with different amounts of red blood cell
      concentrates (RCC). In all patients, a liver iron overload was measured by super
      conducting interference device (SQUID) biosusceptometry and magnetic resonance
      imaging (MRI). MRI is a rapid, noninvasive, and widely available method of
      determining early myocardial iron overload caused by multiple blood transfusion
      due to anemia during polychemotherapy.

PMID- 18623224
TI  - Cefepime-induced neutropenia in a teenager.

PMID- 18623225
TI  - Antioxidant status in pediatric acute lymphocytic leukemia (ALL) and solid
      tumors: the impact of oxidative stress.
AB  - BACKGROUND: Pediatric ALL patients are subjected to an aggressive and continuous
      chemotherapy protocol, while solid tumor patients have a less intensive
      treatment. We studied the antioxidant status of children from the two groups and
      hypothesized that the antioxidant status will differ in concert with their
      treatment. PROCEDURE: The antioxidant status in plasma of seven ALL children and
      that of six children treated for different solid tumors, in regard to the
      different treatment regimen, was compared with healthy controls. These samples
      were taken during therapy, just before the next cyclophosphamide treatment, to
      determine the accumulative oxidative stress. RESULTS: Children from the ALL group
      (n = 7) had significantly lower thiol plasma levels than controls (P < 0.01) and
      their antioxidant capacity as measured by the ferric reducing ability of plasma
      (FRAP) was significantly lower (P < 0.01). These parameters were normal in the
      solid tumors group (n = 6) but plasma antioxidant capacity as measured by the 2,2
      diphenyl-1-picrylhydrazyl (DPPH) assay was significantly lower (P < 0.01).
      CONCLUSIONS: Both groups had impaired plasma antioxidant status. The higher
      oxidative stress of children with ALL is associated with the protocol for
      treating ALL which is much more aggressive and frequent than that of the solid
      tumors. The lower antioxidant status in plasma with ALL children is probably
      associated with increased reactive oxygen species (ROS) as indicated by the
      decrease of the antioxidant activity. This oxidative stress may lead to cell
      death or greater sensitivity of the tumor cell to therapy, with better outcome
      for pediatric patients with ALL.

PMID- 18623226
TI  - Temperature effects on the aerobic metabolism of glycogen-accumulating organisms.
AB  - Short-term temperature effects on the aerobic metabolism of glycogen-accumulating
      organisms (GAO) were investigated within a temperature range from 10 to 40
      degrees C. Candidatus Competibacter Phosphatis, known GAO, were the dominant
      microorganisms in the enriched culture comprising 93 +/- 1% of total bacterial
      population as indicated by fluorescence in situ hybridization (FISH) analysis.
      Between 10 and 30 degrees C, the aerobic stoichiometry of GAO was insensitive to
      temperature changes. Around 30 degrees C, the optimal temperature for most of the
      aerobic kinetic rates was found. At temperatures higher than 30 degrees C, a
      decrease on the aerobic stoichiometric yields combined with an increase on the
      aerobic maintenance requirements were observed. An optimal overall temperature
      for both anaerobic and aerobic metabolisms of GAO appears to be found around 30
      degrees C. Furthermore, within a temperature range (10-30 degrees C) that covers
      the operating temperature range of most of domestic wastewater treatment systems,
      GAOs aerobic kinetic rates exhibited a medium degree of dependency on temperature
      (theta = 1.046-1.090) comparable to that of phosphorus accumulating organisms
      (PAO). We conclude that GAO do not have metabolic advantages over PAO concerning
      the effects of temperature on their aerobic metabolism, and competitive
      advantages are due to anaerobic processes.

PMID- 18623227
TI  - QCM-D sensitivity to protein adsorption reversibility.
AB  - Using a quartz crystal microbalance with dissipative monitoring (QCM-D) we have
      determined the adsorption reversibility and viscoelastic properties of
      ribonuclease A adsorbed to hydrophobic self-assembled monolayers. Consistent with
      previous work with proteins unfolding on hydrophobic surfaces, high protein
      solution concentrations, reduced adsorption times, and low ammonium sulfate
      concentrations lead to increased adsorption reversibility. Measured rigidity of
      the protein layers normalized for adsorbed protein amounts, a quantity we term
      specific dissipation, correlated with adsorption reversibility of ribonuclease A.
      These results suggest that specific dissipation may be correlated with changes in
      structure of adsorbed proteins.

PMID- 18623230
TI  - A novel recycle batch immobilized cell bioreactor for propionate production from
      whey lactose.
AB  - Recycle batch fermentations using immobilized cells of Propionibacterium
      acidipropionici were studied for propionate production from whey permeate, de
      lactose whey permeate, and acid whey. Cells were immobilized in a spirally wound
      fibrous sheet packed in a 0.5-L column reactor, which was connected to a 5-L
      stirred tank batch fermentor with recirculation. The immobilized cells bioreactor
      served as a breeder for these recycle batch fermentations. High fermentation
      rates and conversions were obtained with these whey media without nutrient
      supplementation. It took approximately 55 h to ferment whey permeate containing
      approximately 45 g/L lactose to approximately 20 g/L propionic acid. Higher
      propionate concentrations can be produced with various concentrated whey media
      containing more lactose. The highest propionic acid concentration obtained with
      the recycle batch reactor was 65 g/L, which is much higher than the normal
      maximum concentration of 35 to 45 g/L reported in the literature. The volumetric
      productivity ranged from 0.22 g/L x h to 0.47 g/L x h, depending on the
      propionate concentration and whey medium used. The corresponding specific cell
      productivity was 0.033 to 0.07 g/L x g cell. The productivity increased to 0.68
      g/L x h when whey permeate was supplemented with 1% (w/v) yeast extract. Compared
      with conventional batch fermentation, the recycle batch fermentation with the
      immobilized cell bioreactor allows faster fermentation, produces a higher
      concentration of product, and can be run continually without significant
      downtime. The process also produced similar fermentation results with nonsterile
      whey media.

PMID- 18623228
TI  - Integration of enzyme, strain and reaction engineering to overcome limitations of
      baker's yeast in the asymmetric reduction of alpha-keto esters.
AB  - We report on the development of a whole-cell biocatalytic system based on the
      popular host Saccharomyces cerevisiae that shows programmable performance and
      good atom economy in the reduction of alpha-keto ester substrates. The NADPH
      dependent yeast reductase background was suppressed through the combined effects
      of overexpression of a biosynthetic NADH-active reductase (xylose reductase from
      Candida tenuis) to the highest possible level and the use of anaerobic reaction
      conditions in the presence of an ethanol co-substrate where mainly NADH is
      recycled. The presented multi-level engineering approach leads to significant
      improvements in product optical purity along with increases in the efficiency of
      alpha-keto ester reduction and co-substrate yield (molar ratio of formed alpha
      hydroxy ester to consumed ethanol). The corresponding alpha-hydroxy esters were
      obtained in useful yields (>50%) with purities of > or =99.4% enantiomeric
      excess. The obtained co-substrate yield reached values of greater than 1.0 with
      acetate as the only by-product formed.

PMID- 18623231
TI  - Working at controlled water activity in a continuous process: the gas/solid
      system as a solution.
AB  - Fusarium solani cutinase and Candida cylindracea lipase were used to catalyze a
      transesterification reaction in a continuous gas/solid bioreactor. In this
      system, a solid phase composed of a packed enzymatic preparation was continuously
      percolated with carrier gas which fed substrate and removed reaction products
      simultaneously. Different conditions of immobilization were used and compared to
      the results obtained with a nonsupported enzyme. The enzymatic activity was found
      to be highly dependent of a key parameter: water activity (a(w)). Biocatalyst
      stability was greatly influenced by water activity and the choice of
      immobilization technique for the enzymatic material. For free and adsorbed
      enzymes, water requirements exhibited optima which corresponded to the complete
      hydration coverage of the protein. These optima presented a good correlation with
      the isotherm sorption curves obtained for the different preparations. In this
      work are reported the results concerning the possibility of using a continuous
      system able to operate at controlled water activity in a heterogeneous medium.
      Lipolytic enzyme in such a system appears to be a new process for the
      biotransformation of volatile esters.

PMID- 18623232
TI  - Performances of a full-scale novel multiplate anaerobic reactor treating cheese
      whey effluent.
AB  - A 450-m(3) multiplate anaerobic reactor (MPAR) has been started-up in April 1992
      for treating wastewater (whey permeate and domestic wastewater) at the Nutrinor
      (Lactel) cheese factory in Chambord (Quebec, Canada). The MPAR consists of four
      superimposed sections. The liquid flows upwards from one section to the next,
      while the gas is collected below each plate and evacuated through side-outlets.
      The wastewater is concurrently distributed at the bottom of the first, second,
      and third sections, as 50%, 33%, and 17% of the total influent stream,
      respectively. Granular anaerobic sludge at an initial concentration of 30 kg of
      volatile suspended solids (VSS) per cubic meter of reactor liquid volume was used
      to inoculate the reactor. Under normal operation of the factory, the chemical
      oxygen demand (COD) concentration of the influent ranged from 20 to 37 kg COD m(
      3). The reactor organic loading rate (OLR) fluctuated between 9 and 14.7 kg COD
      m(-3) d(-1) for hydraulic retention times (HRT) maintained between 55 and 68 h.
      At the highest OLR, the MPAR showed an efficiency of 98% and 92% for soluble and
      total COD removal, respectively, and a methane production rate averaging around 4
      m(3) m(-3) d(-1).Biomass-specific activities ranged between 7 and 51, 1.3 and
      8.5, 5.3 and 12.2, 60 and 119, and 119 and 211 mmol g(-1) VSS d(-1) for glucose,
      propionate, acetate, formate, and hydrogen, respectively. Average equivalent
      diameter of the granules was around 0.65 mm. The MPAR reactor generally showed a
      large capacity for solid retention with a biomass content between 32 and 37 kg
      VSS m(-3).

PMID- 18623233
TI  - Effects of sorbitol addition on the action of free and immobilized hydrolytic
      enzymes in organic media.
AB  - The effect of the addition of sorbitol on the activity and stability of enzymes
      was examined by monitoring transesterification reactions performed in organic
      media at various water activities (a(w) = 0.08 to 0.97). Lipases from
      Chromobacterium viscosum and Candida rugosa immobilized on celite, and
      chymotrypsin, free or immobilized on celite, were used. When the sorbitol
      containing enzymes were employed, higher reaction rates and less hydrolysis were
      observed. Immobilization of chymotrypsin resulted in high activity and
      operational stability, while the nonimmobilized enzyme was stable only in the
      presence of sorbitol. The activity of all preparations diminished after washing
      them with pyridine to remove sorbitol. Furthermore, severe stability problems
      occurred in the preparations lacking sorbitol. Sorbitol treatment, even after
      removal of the sorbitol itself, improved the activity of nonimmobilized
      chymotrypsin relative to the washed control. On the other hand, washing to remove
      sorbitol had a negative effect on the activity of both coimmobilized lipase and
      coimmobilized chymotrypsin. Addition of a substrate analogue, N-acetyl-L
      phenylalanine, to chymotrypsin yielded a preparation that exhibited higher
      activity than both the control and its sorbitol-containing counterpart.
      Differential scanning calorimetry measurements revealed that the chymotrypsin
      sorbitol complex was stable against thermal denaturation, undergoing transition
      at a high temperature (89 degrees C). The transition temperatures of the
      substrate-containing chymotrypsin and of the control were identical (72 degrees
      C).

PMID- 18623234
TI  - Fluid shear effects on suspension cultures of Morinda citrifolia.
AB  - The shear susceptibility of cell suspension cultures of the plant cell Morinda
      citrifolia was investigated by subjecting the cells to the well-defined shear
      field generated in turbulent flow through a capillary. Suspensions were
      circulated using a peristaltic pump and average shear stresses between 25 and 350
      N m(-2) were generated in the capillary test section. Control experiments were
      performed to assess the possible contribution of the peristaltic pump to the
      observed cell damage. There was clear evidence of pump-induced damage at the more
      severe test conditions and all viability measurements were corrected accordingly.
      Both shake flask suspension cultures (aged between 9 and 15 days) and repeated
      batch fermentation cultures, grown in a stirred tank reactor (STR) under a
      variety of controlled agitation conditions, were tested in the capillary shear
      loop. The cell damage incurred was evaluated in terms of suspension viability, as
      determined by a dye exclusion technique. Viability loss was found to conform
      closely to a first-order model in which the rate constant was observed to
      increase with the imposed shear stress. Furthermore, a linear relationship was
      identified between the specific death constant and the cumulative energy
      dissipated. Post-shear morphological measurements showed that the chain length
      distribution is shifted toward markedly lower values. In comparison with shake
      flask cultures, repeated batch fermentation cultures exhibited a marked increase
      in sensitivity to capillary shear. Based upon the determined morphological
      characteristics, this result is primarily attributable to the increased chain
      lengths characteristic of the repeated batch cultures.

PMID- 18623235
TI  - Controlling enzyme-catalyzed regioselectivity in sugar ester synthesis.
AB  - The rational control over enzyme-catalyzed regioselectivity has been studied
      using sucrose acylation by vinyl esters in organic media as a model. Subtilisins
      BPN' and Carlsberg preferentially acylate at the 1'-hydroxyl of sucrose with some
      acylation observed at the 6-hydroxyl. The preference for the 1'-hydroxyl is
      strongly affected by the hydrophobicity of the organic solvent and the chain
      length of the vinyl ester. Increasingly hydrophobic solvents and longer chain
      lengths lower the favorable formation of the 1'-acylation and improve 6
      acylation. Molecular modeling of sucrose in the binding pocket of subtilisin BPN'
      shows that the 1'-acylation is favored in solvents that can solvate sugars (such
      as pyridine) as the glucose moiety is exposed to the medium, whereas 6-acylation
      leaves the entire sucrose molecule buried within the enzyme's binding pocket.
      Thus, 1'-acylation is sterically more favorable than 6-acylation. Increasingly
      hydrophobic solvents affect regioselectivity by changing the degree of solvation
      of the glucose moiety in the medium and forcing the sucrose 1'-ester completely
      into the binding pocket. In a related modeling, the vinyl ester chain length was
      shown to modulate regioselectivity by controlling the bond angles between the
      resulting acylenzymes and the sucrose thereby affecting the positioning of the
      sucrose in the binding pocket of subtilisin BPN'. This study shows that control
      over enzymic regioselectivity can be achieved by rational choices of substrate
      and solvent.

PMID- 18623236
TI  - Relation between dissolved oxygen concentration and ajmalicine production rate in
      high-density cultures of Catharanthus roseus.
AB  - The relation between dissolved oxygen (DO) and the ajmalicine production rate of
      Catharanthus roseus was investigated in 15-L tank reactors at constant stirrer
      speed and gas flow rate. Below a DO concentration of 29% of air saturation the
      ajmalicine production rate was less than 0.06 micromol/g/d. Above a DO of 43% the
      ajmalicine production rate was constant at 0.21 micromol/g/d. Between a DO of 29%
      and 43% there was a strong relation between the ajmalicine production rate and
      the DO concentration. After a period of at least 12 days at DO <or=29% the
      culture lacked the ability to adapt to a DO >or=57%. A kinetic equation is
      proposed for the relation between DO and the specific ajmalicine production rate.

PMID- 18623237
TI  - Transformation capacities of chlorinated organics by mixed cultures enriched on
      methane, propane, toluene, or phenol.
AB  - The degradation of trichloroethylene (TCE), chloroform (CF), and 1,2
      dichloroethane (1,2-DCA) by four aerobic mixed cultures (methane, propane,
      toluene, and phenol oxidizers) grown under similar chemostat conditions was
      measured. Methane and propane oxidizers were capable of degrading both saturated
      and unsaturated chlorinated organics (TCE, CF, and 1,2-DCA). Toluene and phenol
      oxidizers degraded TCE but were not able to degrade CF, 1,2-DCA, or other
      saturated organics. None of the cultures tested were able to degrade
      perchloroethylene (PCE) or carbon tetrachloride (CC(4)). For the four cultures
      tested, degradation of each of the chlorinated organics resulted in cell
      inactivation due to product toxicity. In all cases, the toxic products were
      rapidly depleted, leaving no toxic residues in solution. Among the four tested
      cultures, the resting cells of methane oxidizers exhibited the highest
      transformation capacities (T(c)) for TCE, CF, and 1,2-DCA. The T(c) for each
      chlorinated organic was observed to be inversely proportional to the chlorine
      carbon ratio (Cl/C). The addition of low concentrations of growth substrate or
      some catabolic intermediates enhanced TCE transformation capacities and
      degradation rates, presumably due to the regeneration of reducing energy (NADH);
      however, addition of higher concentrations of most amendments reduced TCE
      transformation capacities and degradation rates. Reducing energy limitations and
      amendment toxicity may significantly affect T(c) measurements, causing a masking
      of the toxicity associated with chlorinated organic degradation.

PMID- 18623238
TI  - Enhancing effect of albumin hydrolysate on ethanol production employing
      Saccharomyces sake.
AB  - The enhancing effect of albumin hydrolysate on ethanol production was
      investigated in ethanol fermentations using Saccharomyces sake. In batchwise
      ethanol production, addition of supplemental albumin hydrolysate and
      phosphatidylcholine, or albumin hydrolysate alone, brought about a more than 60%
      increase in final ethanol concentration (148 or 144 g/L compared with 88 g/L with
      no supplementation [control] after 72 h). The effect of the supplements is
      believed to be due to an enhanced alcohol tolerance of cells grown in media
      containing the supplements. Cells grown in media containing albumin hydrolysate
      were enriched in phenyalanine, tyrosine, and methionine in their plasma
      membranes. All three amino acids were also present in considerable amounts in the
      albumin hydrolysate. This fact suggests that the three amino acids, which are
      present in albumin hydrolysate, are incorporated into the plasma membranes of
      cells. Under ethanol production conditions in which only one amino acid among the
      components of albumin hydrolysate was excluded, namely phenlalanine, tyrosine, or
      methionine, significant reductions in ethanol production resulted.

PMID- 18623239
TI  - Diffusion of Cu2+ in calcium alginate gel beads: further analyses.
AB  - The diffusivity of Cu(2+), as determined by previous authors from analysis of
      experimental data in terms of the shrinking core (SCM) and linear absorption
      (LAM) models, is examined in light of the ability of the models to curve fit all
      the data. It is concluded from this further analysis that previous conclusions
      depicting the LAM to have an advantage over the SCM for predictive value are not
      justified. It is also shown that equally good curve fits can be obtained with a
      recent absorption/desorption model of diffusion which considers directly, through
      distribution theory, the effect of heterogeneity of material properties on the
      rate of diffusion.

PMID- 18623240
TI  - Metal recognition by in-vitro selection.
AB  - We propose an in vitro selection strategy to identify bacteriophage variants that
      recognize metal ions in solution. In 6 M urea, phage T7 loses 99.9% of its
      activity in less than 5 min. Inactivation is accelerated by gold, but slowed by
      zinc and magnesium. Selection of phage over five generations in the presence of
      gold, zinc, and magnesium increases phage half-lives 4-, 10-, and 70-fold,
      respectively. As selections are repeated, phage become increasingly dependent on
      the specific metal employed in the selection, indicating the suitability of the
      strategy for optimization of metal-ion recognition.

PMID- 18623241
TI  - Genomic analysis of cancer tissue reveals that somatic mutations commonly occur
      in a specific motif.
AB  - Somatic mutations are hallmarks of cancer progression. We sequenced 26 matched
      human prostate tumor and constitutional DNA samples for somatic alterations in
      the SRD5A2, HPRT, and HSD3B2 genes, and identified 71 nucleotide substitutions.
      Of these substitutions, 79% (56/71) occur within a WKVnRRRnVWK sequence (a novel
      motif we call THEMIS [from the ancient Greek goddess of prophecy]: W=A/T, K=G/T,
      V=G/A/C, R=purine (A/G), and n=any nucleotide), with one mismatch allowed.
      Literature searches identified this motif with one mismatch allowed in 66%
      (37/56) of the somatic prostate cancer mutations and in 74% (90/122) of the
      somatic breast cancer mutations found in all human genes analyzed. We also found
      the THEMIS motif with one allowed mismatch in 88% (23/26) of the ras1 gene
      somatic mutations formed in the sensitive to skin carcinogenesis (SENCAR) mouse
      model, after induction of error-prone DNA repair following mutagenic treatment.
      The high prevalence of the motif in each of the above mentioned cases cannot be
      explained by chance (P<0.046). We further identified 27 somatic mutations in the
      error-prone DNA polymerase genes pol eta, pol kappa, and pol beta in these
      prostate cancer patients. The data suggest that most somatic nucleotide
      substitutions in human cancer may occur in sites that conform to the THEMIS
      motif. These mutations may be caused by "mutator" mutations in error-prone DNA
      polymerase genes.

PMID- 18623245
TI  - Death mechanisms of animal cells in conditions of intensive agitation.
AB  - The question is addressed as to whether cells which are subject to high-energy
      dissipation rates in agitated bioreactors show an apoptotic response. Murine
      hybridoma cells in batch culture were agitated in bench-scale (1-L) bioreactors
      without gas sparging. At an energy dissipation rate of 1.5 W m(-3) there was no
      apparent damage. At 320 W m(-3) cell viability declined, and increasing
      proportions of the dead cells displayed the morphological features of apoptosis,
      but necrosis also remained as a significant mechanism of death. When cells were
      subjected to the intensive energy dissipation rate of 1870 W m(-3) in a
      bioreactor without gas headspace, the cell number dropped by 50% within 2 h and a
      subpopulation of smaller-sized cells emerged. This excluded trypan blue but
      showed some apoptotic characteristics such as reduced and condensed DNA content
      and low F-actin content. The incidence of apoptotic activity was further
      demonstrated by the appearance of numerous apoptotic bodies. Analysis of the cell
      cycles of both small and normal size populations indicated that greater
      proportions of S and G2 cells had become apoptotic and there was evidence of
      preferential survival of G1 cells. It is suggested that two mechanisms of cell
      death are apparent in hydrodynamically stressful situations, but their relative
      expression depends on the energy dissipation rate.

PMID- 18623243
TI  - The translocation of signaling molecules in dark adapting mammalian rod
      photoreceptor cells is dependent on the cytoskeleton.
AB  - In vertebrate rod photoreceptor cells, arrestin and the visual G-protein
      transducin move between the inner segment and outer segment in response to
      changes in light. This stimulus dependent translocation of signalling molecules
      is assumed to participate in long term light adaptation of photoreceptors. So far
      the cellular basis for the transport mechanisms underlying these intracellular
      movements remains largely elusive. Here we investigated the dependency of these
      movements on actin filaments and the microtubule cytoskeleton of photoreceptor
      cells. Co-cultures of mouse retina and retinal pigment epithelium were incubated
      with drugs stabilizing and destabilizing the cytoskeleton. The actin and
      microtubule cytoskeleton and the light dependent distribution of signaling
      molecules were subsequently analyzed by light and electron microscopy. The
      application of cytoskeletal drugs differentially affected the cytoskeleton in
      photoreceptor compartments. During dark adaptation the depolymerization of
      microtubules as well as actin filaments disrupted the translocation of arrestin
      and transducin in rod photoreceptor cells. During light adaptation only the
      delivery of arrestin within the outer segment was impaired after destabilization
      of microtubules. Movements of transducin and arrestin required intact
      cytoskeletal elements in dark adapting cells. However, diffusion might be
      sufficient for the fast molecular movements observed as cells adapt to light.
      These findings indicate that different molecular translocation mechanisms are
      responsible for the dark and light associated translocations of arrestin and
      transducin in rod photoreceptor cells.

PMID- 18623246
TI  - The protective effect of specific medium additives with respect to bubble
      rupture.
AB  - A significant degree of cell damage is observed during suspension cell culture
      with air sparging. Protective agents can be added to the culture medium to
      protect the cells from damage. It has been observed that cells tend to adhere to
      air-medium interfaces and cell damage is mainly due to this cell-bubble
      interaction; protective additives have been found to prevent this cell adhesion
      to the bubble surfaces. In this article, it is demonstrated that the interfacial
      tension between the air and medium is related to the effectiveness of the
      protective additives to prevent adhesion of cells to this interface. Five
      different types of additives (Pluronic F-68, Methocels, dextran, Polyvinyl
      alcohol, and polyethylene glycols) were studied in an effort to determine their
      protective characteristics. Liquid-vapor interfacial tensions of the culture
      medium, with and without the additives, were measured by two different techniques
      (maximum bubble pressure method and Wilhelmy plate method). In addition,
      visualization techniques showed that in the presence of certain protective
      additives cells do not adhere to the bubble surface. Results obtained from these
      experiments indicate that the additives which rapidly lower the liquid-vapor
      interfacial tension of the culture medium also prevent adhesion of cells to the
      bubble surface. Experiments have also been conducted to determine the number of
      cells killed due to bubble rupture, and it was observed that this number is
      related to the amount of cells adhering to the bubble surface.

PMID- 18623247
TI  - Dynamics of biofilm detachment in biofilm airlift suspension reactors.
AB  - The dynamic change in the overall detachment rate of spherical biofilms in a
      biofilm airlift suspension reactor was measured after a downshift of the
      substrate loading rate to zero while all other conditions remained constant. In
      contrast to the expectations, the overall detachment rate decreased rapidly to a
      nearly stable level. Correlations available from literature were not able to
      describe this phenomenon. Concepts were formulated which can describe the
      observations from this study. Research under dynamic conditions and careful
      monitoring of the biofilm surface area and biofilm morphology are necessary to
      elucidate and discriminate biofilm detachment mechanisms.

PMID- 18623248
TI  - Amplification of toluene dioxygenase genes in a hybrid Pseudomonas strain to
      enhance the biodegradation of benzene, toluene, and p-xylene mixture.
AB  - A hybrid metabolic pathway through which benzene, toluene, and p-xylene (BTX)
      mixture could be simultaneously mineralized was previously constructed in
      Pseudomonas putida TB101 (Lee, Roh, Kim, Biotechnol. Bioeng 43: 1146-1152, 1994).
      In this work, we improved the performance of the hybrid pathway by cloning the
      todC1C2BA genes in the broad-host-range multicopy vector RSF1010 and by
      introducing the resulting plasmid pTOL037 into P. putida mt-2 which harbors the
      archetypal TOL plasmid. As a result, a new hybrid strain, P. putida TB103,
      possessing the enhanced activity of toluene dioxygenase in the hybrid pathway was
      constructed. The degradation rates of benzene, toluene, and p-xylene by P. putida
      TB103 were increased by about 9.3-, 3.7-, and 1.4-fold, respectively, compared
      with those by previously constructed P. putida TB101. Apparently, this improved
      capability of P. putida TB103 for the degradation of BTX mixture resulted from
      the amplification of the todC1C2BA genes. Furthermore, a relatively long lag
      period for benzene degradation observed when P. putida TB101 was used for the
      degradation of BTX mixture at low dissolved oxygen (DO) tension disappeared when
      P. putida TB103 was employed.

PMID- 18623249
TI  - Evaluation and applications of optical cell density probes in mammalian cell
      bioreactors.
AB  - On-line optical cell density probes were implemented to continuously monitor the
      cell densities in mammalian cell bioreactor and to achieve advanced bioreactor
      controls. We tested cell density probes from six manufacturers in high cell
      density bioreactors. When externally calibrated, Aquasant and Ingold
      backscattering probes produced the most linear probe responses (PR) versus cell
      density (CD), followed by the ASR and Cerex laser probes. Monitek and Wedgewood
      transmission probes had lower resolutions. All probes were tested in two murine
      hybridoma fermentations. Cell densities varied between 1 x 10(6) cells/mL to 20 x
      10(6) cells/mL and the bioreactors were operated for 5 to 7 weeks. For our
      bioreactors, Aquasant, Ingold, ASR, Wedgewood, and Monitek probes gave
      satisfactory responses. Little fouling was observed with any probe at the end of
      2 weeks. Fouling was a possibility after 3 weeks in one bioreactor but its effect
      can be easily corrected. Cell density control and specific perfusion control of
      bioreactors based on the Aquasant probe were achieved. Implementation of cell
      density probe based perfusion control, instead of "step perfusion adjustments"
      based on manual hemacytometer control, will result in smoother operation,
      healthier cultures, increased medium delivery efficiency, and reduced operational
      excursions.

PMID- 18623250
TI  - Quantitative analysis of biofilm thickness variability.
AB  - The thickness variability of biofilms of Pseudomonas aeruginosa, Klebsiella
      pneumoniae, and the binary population combination of these two species was
      quantified. The experimental method involved cryoembedding biofilms with a
      commercial tissue embedding agent, sectioning, and applying image analysis to
      construct thickness profiles along linear transects (up to 1 cm in length) across
      the substratum. Biofilms embedded and sectioned by this method were locally as
      thin as a single cell attached to the surface (<5 microm) and as thick as 1000
      microm. Week-old biofilms of three different species compositions displayed
      distinct structural features as indicated by their mean thicknesses and by a
      roughness coefficient. Monopopulation biofilms of P. aeruginosa (29 microm mean
      thickness) or K. pneumoniae (100 microm mean thickness) were thinner than the
      binary population biofilm (400 microm mean thickness). A roughness coefficient
      developed in this investigation corroborated the qualitative visual
      characterization of P. aeruginosa biofilms as relatively uniformly thick (mean
      roughness coefficient 0.15), K. pneumoniae biofilms as patchy (mean roughness
      coefficient 1.14), and the binary population biofilm as intermediate (mean
      roughness coefficient 0.26). Whereas P. aeruginosa and binary population biofilms
      covered the substratum completely, significant areas of essentially bare
      substratum were apparent in K. pneumoniae biofilms. The patchiness of K.
      pneumoniae biofilms may be due to the fact that this organism is nonmotile. A
      spatial correlation analysis of the thickness data indicated that thickness
      measurements were still correlated even when separated by distances that exceeded
      the mean biofilm thickness. Cell aggregates, some of them hundreds of microns in
      size, were observed in the effluent of K. pneumoniae and binary population
      biofilm reactors. Measurements of thickness variability and other observations
      reported in this article provide a quantitative basis for analysis of microscale
      structural heterogeneity of biofilms.

PMID- 18623251
TI  - Continuously coupled transcription-translation system for the production of rice
      cytoplasmic aldolase.
AB  - A continuously coupled cell-free transcription-translation system was developed
      for the production of rice cytoplasmic aldolase, an enzyme involved in both
      glycolytic and gluconeogenic pathways in eukaryotic cells. The system works with
      a continuous flow of feeding solution containing nucleoside triphosphates and
      amino acids into a 1-mL reactor containing wheat-germ extract, plasmid DNA, and
      transcription enzyme, and continuous removal of translation product through an
      ultrafiltration membrane fitted in the reactor. Addition of free nucleotide
      primer, m(7)G(5')ppp(5')G, to this reactor was necessary for efficient
      transcription, thus producing biologically active mRNA for translation. The rate
      of aldolase synthesis was constant during the continuous translation reaction. It
      was observed that from 3 h onward only aldolase was synthesized by the system.
      After 30 h, the total amount of protein synthesized reached 205.6 microg, which
      is comparable with the amount synthesized (255.6 microg) in the translation
      system only where separately prepared capped mRNAs were added to the reactor for
      translation. Autoradiogram and Western blot analyses of the translated product
      showed a distinct band corresponding to the calculated molecular weight of the
      protein. These results have shown the establishment of a continuously coupled
      eukaryotic transcription-translation system for the expression of genes from
      eukaryotic cells.

PMID- 18623252
TI  - Aqueous extraction of sugarcane bagasse hemicellulose and production of xylose
      syrup.
AB  - At the optimum level of severity, the aqueous extraction of sugarcane bagasse, an
      abundant agricultural residue, gave, depending on the degree of comminution, 60%
      to 89% yield of xylose, most of it in the form of a water soluble xylan. A
      process for producing xylose-rich syrups was conceived and tested, consisting of
      aqueous extraction, acid hydrolysis of the concentrated aqueous extract
      centrifugal clarification of the hydrolysate, and recovery of the acid by
      continuous ion exclusion. The cost estimate indicates operating costs on the
      order of $0.12 to $0.15/kg xylose, in the form of xylose-rich molasses.

PMID- 18623253
TI  - Determination of the respiration quotient in mammalian cell culture in
      bicarbonate buffered media.
AB  - The determination of the respiration quotient (RQ = CER/OUR) has not been used so
      far as a tool for understanding animal cell metabolism. This is due to problems
      in measuring the carbon dioxide evolution rate (CER) rather than the oxygen
      uptake rate (OUR). The determination of the CER is complicated by the use of
      bicarbonate in the medium. Using liquid and gas balances we have derived an
      equation for continuous culture to quantify the amount of CO(2) that comes from
      the bicarbonate in the feed. Under cell-free conditions, values predicted by this
      equation agree within 4% with the experimental results. In continuous culture
      using hybridoma cells, the CO(2) from the feed, as determined by an IR-gas
      analyzer, was found to represent a significant amount of the total measured CO(2)
      in the off-gas (50% in a suboptimal, and 30% in high-growth medium). Furthermore,
      the problem of CO(2) loss from the medium during medium preparation and storage
      was solved using both a theoretical and an experimental approach. RQ values in
      continuous culture were evaluated for two different growth media. Small but
      significant differences in RQ were measured, which were matched by differences in
      specific antibody rates and other metabolic quotients. In a medium with Primatone
      RL, an enzymatic hydrolysate of animal cell tissue that causes a more than
      twofold increase in cell density, the RQ was found to be 1.05, whereas in medium
      without Primatone RL (but containing amino acids equivalent in composition and
      concentration to Primatone RL) the RQ was found to be 0.97. We suggest the RQ to
      be a useful parameter for estimating the physiological state of cells. Its
      determination could be a suitable tool for both the on-line control of animal
      cell cultivations and the understanding of cell metabolism.

PMID- 18623254
TI  - Mass balancing in kinetic resolution: calculating yield and enantiomeric excess
      using chiral balance.
AB  - When kinetic resolution is applied for the production of enantiomerically pure
      compounds, process options may be used which involve more than one chiral
      substrate and one chiral product, such as sequential or parallel enzymatic
      kinetic resolutions or hydrolysis of diastereomers. Although the relation between
      the yields (y) of the chiral compounds is straightforward in these cases, the
      relation between their enantiomeric excess (ee) values is not. Combining mass
      balances into a so-called chiral balance (Sigma y x ee(R) = 0) provides the
      relation between enantiomeric excess values in a useful manner. This chiral
      balance easily shows which nonmeasured enantiomeric excess values and yields can
      be calculated from measured values. The chiral balance is only valid when
      configurations at chiral centers are conserved.

PMID- 18623256
TI  - Studies on the lipozyme-catalyzed synthesis of butyl laurate.
AB  - The effects of temperature, speed of agitation, enzyme concentration, etc., on
      butyl laurate synthessis using Mucor miehei lipase (Lipozymetrade mark) have been
      studied. Although the soluble enzyme was quite thermcstable in aqeous solution,
      it deactivated rapidly at and above 40 degrees C in the presence of butanol. This
      enzyme immobilized on an anion-exchange resin (Lipozymetrade mark) showed
      enhanced stability (as compared to the soluble form) to denaturation by butanol
      under the same conditions. The denaturation of M. miehei lipase was found to be a
      function of the butanol concentration in the aqueous phase, and rapid
      denaturation takes place at the concentration corresponding to its saturation at
      that temperature. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623257
TI  - Occurrences at mineral-bacteria interface during oxidation of arsenopyrite by
      Thiobacillus ferrooxidans.
AB  - The combination of an improved bacterial desorption method, scanning electron
      microscopy (SEM), diffuse reflectance and transmission infrared Fourier transform
      spectroscopy, and a desorption-leaching device like high-pressure liquid
      chromatography (HPLC) was used to analyze bacterial populations (adhering and
      free bacteria) and surface-oxidized phases (ferric arsenates and elemental
      sulfur) during the arsenopyrite biooxidation by Thiobacillus ferrooxidans. The
      bacterial distribution, the physicochemical composition of the leachate, the
      evolution of corrosion patterns, and the nature and amount of the surface
      oxidized chemical species characterized different behavior for each step of
      arsenopyrite bioleaching. The first step is characterized by a slow but strong
      adhesion of bacteria to mineral surfaces, the appearance of a surface phase of
      elemental sulfur, the weak solubilization of Fe(II), As(III), and As(V), and the
      presence of the first corrosion patterns, which follow the fragility zones and
      the crystallographic orientation of mineral grains. After this short step, growth
      of the unattached bacteria begins, while ferrous ions in solution are oxidized by
      them. Ferric ions produced by the bacteria can oxidize the sulfide directly and
      are regenerated by Fe(II) bacterial oxidation. At this time, a bioleaching cycle
      takes place and a coarse surface phase of ferric arsenate (FeAsO(4) . xH(2)O
      where x approximately 2) and deep ovoid pores appear. At the end of the
      bioleaching cycle, the high concentration of Fe(III) and As(V) in solution
      promotes the precipitation of a second phase of amorphous ferric arsenate
      (FeAsO(4) . xH(2)O where x approximately 4) in the leachate. Then the
      biooxidation process ceases: The bacteria adhering to the mineral sufaces are
      coated by the ferric arsenates and the concentration of Fe(III) on the leachate
      is found to have decreased greatly. Both oxidation mechanisms (direct and
      indirect oxidation) have been stopped. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623258
TI  - Effect of cDNA copy number on secretion rate of activated protein C.
AB  - The secretion rate of activated protein C (APC) by BHK cells was increased 35
      fold by increasing the cDNA copy number per cell from 50 to 240. In this range,
      the relation between APC secretion and cDNA copy number was not linear and the
      rate of APC secretion per cDNA copy increased sevenfold. This apparent
      cooperative effect of multiple cDNA copies could be related to their integration
      in tandem. For cDNA copy numbers higher than 240, the APC secreation rate per
      cDNA and per cell decreased dramatically. The gamma-carboxylation of glutamic
      acid residues, a posttranslational modification required for APC biological
      activity, was also investigated. The proportion of APC that was fully gamma
      carboxylated decreased as the secretion rate of APC increased. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623259
TI  - Properties of microfiltration membranes: Mechanisms of flux loss in the recovery
      of an enzyme.
AB  - The transmission and rate of filtration of the enzyme yeast alcohol dehydrogenase
      (YADH) has been studied at capillary pore microfiltration membranes. Photon
      correlation spectroscopy (PCS) with nanometer resolution showed that the enzyme
      existed as discreate molecules only for a narrow range of pH and ionic strength.
      Under such conditions, the transmission of the enzyme was high. However, the rate
      of filtration still decreased continuously with time. Analyssis of the time
      dependence of the rate of filtration indicated that this decrease was due to in
      pore enzyme deposition at low concentration ("standard blocking model") and
      suface depositon at high concentration ("cake filtration model"). Use of atomic
      force microscopy (AFM) gave unequivocal and quantitative confirmation of these
      inferences. The work shows the great advantage of using advanced physical
      characterization techniques, both for the identification of the optimum
      conditions for filtration (PCS) and for the elucidation of mechanisms giving rise
      to inefficiencies in the filtration process (AFM). (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623260
TI  - Effects of substrate branching characteristics on kinetics of enzymatic
      depolymerization of mixed linear and branched polysaccharides: II.
      Amylose/glycogen alpha-amylolysis.
AB  - Enzymatic depolymerization of polysaccharides with alpha-amylase has been studied
      in mixed aqueous dimethylsulfoxide (DMSO)/water solvents. Polysaccharide
      substrate chemical compositions, configurational structures, and bonding pattersn
      are known to affect observed enzymatic reaction kinetics. The branching
      structures of polysaccharides and their effects on the kinetic mechanisms of
      depolymerization reactions via endo-acting hydrolyzing enzyme was studied via
      size exclusion chromatography coupled to low angle laser light scattering
      (SEC/LALLS). The glycogen branching structure is a heterogeneously distributed
      "cluster" structure rather than a homogeneously distributed "treelike" structure.
      The action pattern of alpha-amylase on glycogen, which is composed of highly
      branched clusters, as end-products, has a "pseudo-exo-attack" in contrast to an
      expected "endoattack" as seen in the hydrolysis of amylose or amylopectin
      substrates. These effects of branched substrates for mixed amylose/glycogen alpha
      amylolysis have been predicted and demonstrated by both experimental and
      theoretical analysis using the kinetic model presented in this report. The
      "lumped" kinetic model employed, assumes that the enzyme simultaneously attacks
      both linear and branched substrates. In general, excellent agreement between the
      model predictions and the experimental observations, both qualitatively and
      quantitatively, was obtained. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623261
TI  - A modeling study of anaerobic biofilm systems: I. Detailed biofilm modeling.
AB  - A detailed model acetate-utilizing methanogenic biofilms accounting for the
      diffusion of neutral and ionic species, chemical equilibrium, electroneutrality,
      gas production within the biofilm, pH-dependent Monod kinetics, and the presence
      of a concentration boundary layer is presented. The model qualitatively fits the
      pH profiles that are reported for acetate-utilizing methanogenic aggregates. A
      sensitivity analysis on the biological parameters showed that the flux of acetate
      is sensitive to the maximum utilization rate, half-saturation constant, and
      biofilm density for the bulk conditions investigated. Criteria when traditional
      biofilm models can be used to predict the flux of acetate into the biofilm are
      established. If the maximum pH change predicted using a hypothetical system is
      within +/-0.05, the traditional model predicts the flux to within +/-5% of the
      value calculated with the model developed in this study. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623262
TI  - A modeling study of anaerobic biofilm systems: II. Reactor modeling.
AB  - A rigorous steady-state model of anaerobic biofilm reactors taking into account
      acid-base and gas-phase equilibria in the reactor in conjunction with detailed
      chemical equilibria and mass transfer in acetate-utilizing methanogenic biofilms
      is presented. The performances of ideal completely stirred tank reactors (CSTRs)
      and plug-flow reactors, as well as reactors with nonideal hydraulic conditions,
      are simulated. Decreasing the surface loading rate increases the acetate removal
      efficiency, while decreasing the influent pH and increasing the buffering
      capacity improves the removal efficiency only if the bulk pH of the reactor
      shifts toward more optimal values between 6.8 to 7.0. The reactor can have
      negative or positive removal efficiencies depending on the start-up conditions.
      The respiration coefficient plays a critical role in determining the minimum
      influent pH required for reactor recovery after failure. Having multiple CSTRs-in
      series generally increases the overall removal efficiency for the influent
      conditions investigated. Monitoring of the influent feed quality is critical for
      plug-flow reactors, becasue failure of the initial sections of the reactor may
      cause a cascading effect that may lead to a rapid reactor failure. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623263
TI  - Genetically engineered charge modifications to enhance protein separation in
      aqueous two-phase systems: Charge directed partitioning.
AB  - This report continues or examination of the effect of genetically engineered
      charge modifications on the partitioning behavior of proteins in aqueous two
      phase extration. The genetic modifications consisted of the fusion of charged
      peptide tails to beta-galactosidase and charge-change point mutations to T4
      lysozyme. Our previous article examined the influence of these charge
      modifications on partitioning as a function of interfacial potential difference.
      In this study, we examined charge directed partitioning behavior in PEG/dextran
      systems containing small amounts of the charged polymers diethylaminoethyl
      dextran (DEAE-dextran) or dextran sulfate. The best results were obtained when
      attractive forces between the protein and polymer were present. Nearly 100% of
      the beta-galactosidase, which carries a net negative charge, partitioned to the
      DEAE-dextran-rich phase regardless of whether the phase was dextran or PEG. In
      these cases, cloudiness of the protein-rich phases suggest that strong charge
      interactions resulted in protein/polymer aggregation, which may have contributed
      to the extreme partitioning. Unlike the potentialdriven partitioning reported
      previously, consistent partitioning trends were observed as a result of the
      fusion tails, with observed shifts in partition coefficient (K(p)) of up to 37
      fold. However, these changes could not be solely attributed to charge-based
      interactions. Similarly, T4 lysozyme, carrying a net positive charge, partitioned
      to the dextran sulfate-containing phase, and displayed four- to sevenfold shifts
      in K(p) as a result of the point mutations. These shifts were two to four times
      stronger than those observed for potential driven partitioning. Little effect on
      partitioning was observed when the protein and polymer had the same charge, with
      the exception of beta-galactosidase with polyarginine tails. The high positive
      charge density of these tails provided for a localized interaction with the
      dextran sulfate, and resulted in 2- to 15-fold shifts in K(p). (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623264
TI  - Factors affecting the esterification of lauric acid using an immobilized
      biocatalyst: Enzyme characterization and studies in a well-mixed reactor.
AB  - The esterification of lauric acid with geraniol catalyzed by the commercially
      immobilized lipase preparation from Mucor miehei, Lipozyme(R), was studied in
      well-stirred flasks. The enzyme support was characterized in terms of its
      internal and external surface area, protein location, and protein content. It was
      found that the enzyme was mainly located on the external surface of the support,
      therefore, internal diffusional limitations were not important. It was also shown
      that the protein content of the support depends on the size of the particle, with
      smaller particles containing higher amounts of protein per unit weight. Under the
      conditions studied, the reaction was not under external mass transfer
      limitations, and the initial reaction rate depended on the size of the support
      particles. This was mainly due to the different protein contents on the support
      as a function of particle size and not to internal or external mass transfer
      limitations. Also, it was found that the inhibition exerted by water was
      predominantly a physical effect due to its accumulation around the enzyme. It was
      also found that the reaction was substrate inhibited by lauric acid, but not by
      geraniol. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623265
TI  - Degradation of quinoline by immobilized Comamonas acidovorans in a three-phase
      airlift reactor.
AB  - Quinolie degradation by Comamonas acidovorans was studied in a continuously
      operated three-phase airlift reactor. Porous glass beads were applied as support
      matrix for cell imobilization by colonization. Under steady-state conditions (S
      approximately 0), cell attachment was poor at low dilution rates but imporved
      considerably with increasing dilution rate. Conversion of quinoline was
      investigated below and above the washout for suspended culture (D(crit) = mu(max)
      = 0.42 h(-1)). With immobilized cells the reactor could be operated at D >
      mu(max), and complete conversion of quinoline was achieved as long as the
      specific quinoline feed rate D*S(0)/X did not exceed the maximum specific
      degradation rate (r(S, max)). The biofilm thickness was about 100 mum, and its
      efficiency was about 54% compared to suspended organisms. If quinoline overloads
      were supplied to the reactor, quinoline, as overloads were supplied to the
      reactor, quinoline, as well as its pathway intermediates, appeared in the reactor
      and conversion was low. Hence, the immobilized microorganisms remained viable and
      active. They could survive quinoline overloads. If the quinoline feed rate was
      reduced agains, complete conversion was reestablished. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623266
TI  - Cell cycle and cell size dependence of susceptibility to hydrodynamic forces.
AB  - Exposure of animal cells to intense hydrodynamic forces exerted in turbulent
      capillary flow, and by controiled agitation and aeration, resulted in
      preferential destruction of S and G(2) cells and the extent of destruction of
      these cells was dependent upon the intensity of the action. The loss of these
      cells was possibly due to their larger size. However, the appearance of large
      numbers of membrane-bound vesicular structures similar to apoptotic bodies as
      well as cells with low DNA stainability (in a sub-G(1) peak) suggested that the
      action of adverse hydrodynamic forces on these large cells may at least in part
      be to induce an apoptotic response. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623268
TI  - Photochemistry of a photosynthetic reaction center immobilized in lipidic cubic
      phases.
AB  - Photosynthetic reaction centers, isolated and purified from the facultative
      phototrophic bacterium Chloroflexus aurantiacus, were immobilized in optically
      transparent lipidic cubic phases composed of 42% (w/w) 1-palmitoyl-2-hydroxy-sn
      glycero-3-phosphocholine and 58% (w/w) water. The immobilized photosynthetic
      protein retains its native properties, as indicated by visible and circular
      dichroic spectra. The ground state visible spectrum of the immobilized reaction
      centers is very similar to the corresponding spectrum in aqueous solution,
      indicating that the protein pigments are not extracted into the lipidic regions
      of the cubic phase. The secondary structure of the protein is maintained in the
      immobilized state, as determined by far-UV circular dichroism spectroscopy in the
      200- to 250-nm range. Moreover, immobilized reaction centers retain their
      photochemical activity: a reversible photo-oxidation of the primary electron
      donor (P) is seen upon continuous illumination. Furthermore, the entrappment of
      reaction centers does not affect the kinetics of charge recombination between the
      photo-oxidized primary donor (P(+)) and the photoreduced primary quinone
      acceptor, generated by a short flash of light. Reaction centers devoided of the
      secondary quinone acceptor can be easily reconstituted in cubic phases by means
      of their coimmobilization with 1,4-naphtoquinone. Indeed, the kinetics for charge
      recombination in reconstituted reaction centers is dramatically slower than the
      corresponding kinetics in the unreconstituted protein. Interestingly, immobilized
      reaction centers are significantly stabilized as compared with reaction centers
      in aqueous solution: the integrity of the protein in the cubic phase is
      maintained for at least 5 months, whereas in water solution 50% of the activity
      is lost within 2 months. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623269
TI  - Surfactant structure effects in protein separations using nonionic
      microemulsions.
AB  - In this article, the extraction of cytochrome c utilizing various nonionic
      surfactant microemulsions has been tested to determine the effect of surfactant
      structure on protein partitioning. Surfactants tested include a linear alcohol
      ethoxylate (Neodol 91-2.5), two alkyl phenol ethoxylates (lgepal CO-520, Trycol
      6985), and a series of alkyl sorbitan esters that are either ethoxylated (Tweens)
      or un-ethoxylated (Spans). Initial attempts to extract hemoglobin into Neodol 91
      2.5 Winsor II microemulsions (oil-continuous) appeared successful based on heme
      estimation. Careful analysis showed that the hemoglobin had dissociated prior to
      extraction and that only the heme was extracted with false positive results. In
      fact, Neodol 91-2.5 microemulsions were unable to extract a variety of proteins
      with differing biophysical properties. Among all the other nonionic surfactant
      microemulsions tested only those made using sorbitan esters extracted significant
      amounts of cytochrome c. The partition coefficients achieved in this study are
      more than an order of magnitude higher than that seen previously in the
      literature for comparable sorbitan systems. However, this partition coefficient
      is extremely sensitive to ionic strength. At an ionic strength as low as 0.001 M,
      the partition coefficient is reduced to that seen in previous studies. We have
      found that protein partitioning in sorbitan ester microemulsions is not a
      function of water content. In addition, extraction is not a function of either
      alkyl chain length, or polyethylene oxide molecular weight. Hence, the sorbitan
      group appears to have an important role in extraction, possibly through a weak
      electrostatic protein-surfactant interaction. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623270
TI  - Enzymatic glucosylation of hydrophobic alcohols in organic medium by the reverse
      hydrolysis reaction using almond-beta-D-glucosidase.
AB  - Alkyl beta-D-glucosides were synthesized from D-glucose and alcohols by reverse
      hydrolysis using the commercially available almond beta-D-glucosidase in 9:1
      (v/v) acetonitrile-water medium. The main characteristics of this enzyme
      catalyzed glucosylation were established by using 2-hydroxybenzyl alcohol. The
      reaction is entirely regio- and stereoselective. The solvent plays a fundamental
      role because, by decreasing the water concentration in the medium, the shift of
      the reaction equilibrium toward synthesis is realized without using an excessive
      amount of alcohol. Nevertheless, a minimum amount of water is necessary to
      maintain the enzyme activity. In contrast to the use of the enzyme in aqueous
      medium, the pH of the added water in acetonitrile did not influence the
      synthesis. Using this procedure, we have conducted systematic glucosylation of
      numerous alcohols and we have investigated enzyme specificity and alcohol
      reactivity. The enzyme has a pronounced affinity for the alcohols containing a
      phenyl group, and enantioselectivity for the aglycon is obtained with 1
      phenylethyl alcohol. Moreover, by using almond beta-D-glucosidase it was also
      possible to synthesize alkyl beta-D-galactosides. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623271
TI  - Metabolic flux distributions in Penicillium chrysogenum during fed-batch
      cultivations.
AB  - Based on a review of the Penicillium chrysogenum biochemistry a stoichiometric
      model has been set up. The model considers 61 internal fluxes and there are 49
      intracellular metabolites which are assumed to be in pseudo-steady state. In
      addition to the intracellular fluxes the model considers the uptake of 21 amino
      acids. From the stoichiometric model the maximum theoretical yield of penicillin
      V is calculated to 0.43 mol/mol glucose. If biosynthesis of cysteine is by direct
      sulfhydrylation rather than by transsulfuration, the maximum theoretical yield is
      about 20% higher, i.e., 0.50 mol/mol glucose. The theoretical yield decreases
      substantially if alpha-aminoadipate is converted to 6-oxo-piperidine-2-carboxylic
      acid (OPC). If only 40% of the alpha-aminoadipate is recycled, the maximum
      theoretical yield is 0.31 mol/mol glucose. The uptake rates of glucose, lactate,
      gamma-aminobutyrate, and 21 amino acids were measured during fed-batch
      cultivations. The rates of formation of penicillin V, delta-(L-alpha)-aminoadipyl
      L-cysteinyl-D-valine (ACV), OPC, and the pool of isopenicillin N, 6-APA, and 8
      HPA were also measured. Finally the synthesis rates of the biomass constituents
      RNA/DNA, protein, lipid, carbohydrate, and amino carbohydrate were measured. From
      these measured rates and the stoichiometric model the metabolic fluxes through
      the different intracellular pathways are calculated. The calculations show that
      penicillin formation is accompanied by a large flux through the pentose phosphate
      (PP) pathway due to a large requirement for nicotinamide-adenine dinucleotide
      phosphate (NADPH) used in the biosynthesis of cysteine. If cysteine is added to
      the medium, the flux through the PP pathway decreases. From the stoichiometric
      model Y(xATP) is calculated to 87 mmol adenosine triphosphate (ATP)/g dry weight
      (DW), and from the flux calculations m(ATP) is found to 3 mmol ATP/g DW/h. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623272
TI  - Assessment of a disc stack centrifuge for use in mammalian cell separation.
AB  - A prototype disc stack centrifuge was tested for the separation of mammalian cell
      cultures from 80- and 2000-L fermentations. The clarification capacity for
      mammalian cells was excellent, but some smaller particles remained in the
      supernatant and reduced its usefulness for downstream processing. In order to
      identify the source of such particle formation, several parameters were assessed
      and minimum particle size for separation was calculated. An analysis of particle
      distribution was performed. Temperature and pressure effects inside the
      centrifuge bowl were measured. Some modifications of mechanical engineering can
      be suggested for the improvement of the use of standard disc stack centrifuges
      for mammalian cells. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623273
TI  - Development of a predictive description of an immobilized-cell, three-phase,
      fluidized-bed bioreactor.
AB  - A fully predictive mathematical description of a three-phase, tapered, fluidized
      bed bioreactor is developed. This mathematical model includes the effects of the
      tapered bed, variable dispersion coefficient, and variable solid holdup upon the
      concentration profiles developed in the bed. In addition, the effect of the
      concentration profile which is developed inside the biocatalyst bead is included
      by means of an effectiveness factor calculation. Using accepted correlations for
      the dispersion coefficient and for the liquid, gas, and solid holdup in the bed,
      the model is fully predictive. The model was found to adequately predict
      experimental obtained concentration profiles. Then, the model was used to examine
      the various phase holdups through the bed and the degree to which the dispersion
      coefficient varied through the bed. The effect of changes in these calculated
      variables upon the reaction rate is discussed. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623274
TI  - Heterogeneity within populations of recombinant Chinese hamster ovary cells
      expressing human interferon-gamma.
AB  - The Chinese hamster ovary (CHO) cell line has great commercial importance in the
      production of recombinant human proteins, especially those for therapeutic use.
      Much attention has been paid to CHO cell population physiology in order to define
      factors affecting product fidelity and yield. Such studies have revealed that
      recombinant proteins, including human interferon-gamma (IFN-gamma), can be
      heterogeneous both in glycosylation and in proteolytic processing. The type of
      heterogeneity observed depends on the growth physiology of the cell population,
      although the relationship between them is complex. In this article we report
      results of a cytological study of the CHO320 line which expresses recombinant
      human IFN-gamma. When grown in suspension culture, this cell line exhibited three
      types of heterogeneity: (1) heterogeneity of the production of IFN-gamma within
      the cell population, (2) heterogeneity of the number of nuclei and mitotic
      spindles in dividing cells, and (3) heterogeneity of cellular environment. The
      last of these arises from cell aggregates which form in suspension culture: Some
      cells are exposed to the culture medium; others are fully enclosed within the
      mass with little or no direct access to the medium. Thus, live cells producing
      IFN-gamma are heterogeneous in their environment, with variable access to O(2)
      and nutrients. Within the aggregates, it appears that live cells proliferate on a
      dead cell mass. The layer of live cells can be several cells deep. Specific cell
      cell attachments are observed between the living cells in these aggregates. Two
      proteins, known to be required for the formation of certain types of
      intercellular junctions, spectrin and vinculin, have been localized to the
      regions of cell-cell contact. The aggregation of the cells appears to be an
      active process requiring protein synthesis. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623275
TI  - Reduction of nitrate and nitrite in a cyclically operated continuous biological
      reactor.
AB  - Biological reduction of nitrate and nitrite was studied with a continuously
      operated cyclic reactor. The medium was fed to the reactor during the first phase
      of the cycle, and the effluent was drawn from the reactor during the third phase
      of the cycle; reaction occurred throughout the cycle. The process was described
      mathematically based on kinetic expressions revealed in an independent study. The
      model equations were subjected to detailed analysis with numerical codes based on
      the bifurcation theory for forced systems. The analysis has shown that in the
      operating parameter space there are extensive regions where the system can reach
      up to three different periodic states. The results of this analysis are shown in
      the form of two-dimensional operating diagrams. Numerical results have also shown
      that under certain operating conditions nitrate can be completely eliminated,
      while nitrite remains practically untreated. An experimental unit was designed,
      constructed, and used in experiments with a strain of Pseudomonas denitrificans
      [American Type Culture Collection (ATCC) 13867] under different operating
      conditions. The experimental results confirmed the theoretical predictions both
      qualitatively and quantitatively. Conditions under which complete reduction of
      both nitrate and nitrite is achieved, were found and experimentally verified. The
      results of this study suggest a methodology for analysis and design of cyclically
      operated bioreactors employed in denitrification of wastewaters. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623276
TI  - Reversed micellar extraction of trypsin: Effect of solvent on the protein
      transfer and activity recovery.
AB  - By using trypsin as the model protein and AOT as the model surfactant, the effect
      of a variety of solvents on protein transfer and activity recovery during the
      liquid-liquid reversed micellar extraction was investigated. It was found that
      several solvents, including isooctane, octane, heptane, and kerosene, had a
      similar effect on the recovery of trypsin activity after a full cycle of forward
      and backward extraction, and could all be used as the solvents for AOT-reversed
      micelles in trypsin extraction. Two other solvents (hexane and cyclohexane),
      however, were not so efficient. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623277
TI  - The oxidation of chiral alcohols catalyzed by catalase in organic solvents.
AB  - The catalytic properties of bovine liver catalase have been investigated in
      organic solvents. In tetrahydrofuran, dioxane, and acetone (all containing 1% to
      3% of water), the enzyme breaks down tert-butyl hydroperoxide several fold faster
      than in pure water. Furthermore, the rate of catalase-catalyzed production of
      tert-butanol from tert-butyl hydroperoxide increases more than 400-fold upon
      transition from aqueous buffer to ethanol as the reaction medium. The mechanistic
      rationale for this striking effect is that in aqueous buffer the rate-limiting
      step of the enzymatic process involves the reduction of catalase's compound I by
      tert-butyl hydroperoxide. In ethanol, and additional step in the reaction scheme
      becomes available in which ethanol, greatly outcompeting the hydroperoxide, is
      oxidized by compound I regenerating the free enzyme. In solvents, such as
      acetonitrile or tetrahydrofuran, which themselves are not oxidizable by compound
      I, catalase catalyzes the oxidation of numerous primary and secondary alcohols
      with tert-butyl hydroperoxide to the corresponding aldehydes or ketones. The
      enzymatic oxidation of some chiral alcohols (2,3-butanediol, citronellol, and
      menthol) under these conditions occurs enantioselectively. Examination of the
      enantioselectivity for the oxidation of 2,3-butanediol in a series of organic
      solvents reveals a considerable solvent dependence. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623278
TI  - Mathematical model of self-cycling fermentation.
AB  - This article presents a mathematical model for biomass, limiting substrate, and
      dissolved oxygen concentrations during stable operation of self-cycling
      fermentation (SCF). Laboratory experiments using the bacterium Acinetobacter
      calcoaceticus RAG-1 and ethanol as the limiting substrate were performed to
      validate the model. A computer simulation developed from the model successfully
      matched experimental SCF intracycle trends and end-of-cycle results and, most
      importantly, settled into an unimposed periodicity characteristic of stable SCF
      operation. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623279
TI  - Enantiomeric separation by using nano-liquid chromatography with on-column
      focusing.
AB  - The present study shows a new nano-liquid chromatographic method for beta-blocker
      enantiomers' separation. This method consists of using a capillary column packed
      with silica particles which were chemically modified with vancomycin. On-column
      focusing allowed to inject relatively high sample volumes (1500 nL) increasing
      method sensitivity. The studied racemic compounds, namely atenolol, propranolol,
      oxprenolol, and metoprolol were dissolved in methanol and injected for
      chromatographic separation. The effect of injected sample volume was studied in
      the range of 50-2100 nL. Peak height of the two alprenolol enantiomers increased
      linearly up to 1500 nL. This volume was injected for validation and sample
      analysis. Under optimal experimental conditions, LODs and LOQs (LOD and LOQ for
      each alprenolol enantiomers) were 9.0 and 15.6 ng/mL, respectively. Calibration
      curves were linear in the studied range (9-250 ng/mL). The optimized method was
      applied to the analysis of a human plasma sample spiked with racemic alprenolol.

PMID- 18623280
TI  - Polymethacrylate monolithic columns for capillary liquid chromatography.
AB  - In recent years, continuous separation media have attracted considerable
      attention because of the advantages they offer over packed columns. This research
      resulted in two useful monolithic material types, the first based on modified
      silica gel and the second on organic polymers. This work attempts to review
      advances in the development, characterization, and applications of monolithic
      columns based on synthetic polymers in capillary chromatography, with the main
      focus on monolithic beds prepared from methacrylate-ester based monomers. The
      polymerization conditions used in the production of polymethacrylate monolithic
      capillary columns are surveyed, with attention being paid to the concentrations
      of monomers, porogen solvents, and polymerization initiators as the system
      variables used to control the porous and hydrodynamic properties of the
      monolithic media. The simplicity of their preparation as well as the
      possibilities of controlling of their porous properties and surface chemistries
      are the main benefits of the polymer monolithic capillary columns in comparison
      to capillary columns packed with particulate materials. The application areas
      considered in this review concern mainly separations in reversed-phase
      chromatography, ion-exchange chromatography, hydrophobic and hydrophilic
      interaction modes; enzyme immobilization and sample preparation in the capillary
      chromatography format are also addressed.

PMID- 18623282
TI  - Evaluation of use of a very short polar microbore column segment in high-speed
      gas chromatography analysis.
AB  - Very fast GC analyses are commonly carried out by using 10 m x 0.1 mm id
      capillaries. In order to achieve rapid elution times (1-3 min), the latter are
      operated under suboptimum conditions. The present research is focused on the
      evaluation of use of a 0.1 mm id polar column segment (2 m), operated under near
      to-optimum conditions, in very fast GC analysis. The results attained are
      compared with those derived from using a 10 m microbore column in very fast GC
      experiments. Prior to method development, the effects of gas velocity,
      temperature program rate, and sample amounts on analytical performance were
      evaluated. Following these preliminary applications, a complex lipidic sample,
      cod liver oil, was subjected to rapid separation (approximately 2.1 min) on the
      10 m capillary through the application of a 50 degrees C/min temperature rate and
      a 130 cm/s gas velocity. The same matrix was analyzed on the 2 m capillary using
      the same temperature program rate and range, but with a close-to-ideal linear
      velocity. The results observed were of interest, as the separation was achieved
      in less time (1.45 min) with improved peak resolution. Finally, both methods were
      validated in terms of retention time and peak area repeatability, LOQ, and
      linearity.

PMID- 18623283
TI  - Effects of alcohols on CE enantioseparation of basic drugs with native gamma-CD
      as chiral selector.
AB  - The effects of alcohol on the CE enantioseparation of selected basic drugs with
      gamma-CD as the chiral selector was investigated. The enantioseparation behavior
      of the analytes with gamma-CD in the absence and presence of different alcohols
      specifically methanol, ethanol, 2-propanol (IPA), and 2-methyl-2-propanol (TBA),
      the relationship of enantiomeric resolution (R(s)) values with either
      hydrophobicity or bulkiness of the alcohols, as well as the effect of these
      alcohols on interaction of the analytes with gamma-CD were studied. Results
      showed that hydrophobicity and/or bulkiness of alcohols have an influence on the
      enantioresolution of most of the analytes based on the relatively high
      correlation coefficients (R) obtained between R(s) versus log P and between R(s)
      versus ovality (i.e., parameter to indicate bulkiness of a molecule). Comparison
      of the values of the average binding constants obtained for each enantiomeric
      pair in the presence and absence of 5% IPA showed that alcohols can increase,
      decrease, or give a minimal effect on the analyte-gamma-CD interaction depending
      on the analyte. Furthermore, the significant enhancement in the enantioresolution
      of both propranolol and pindolol in the presence of either IPA or TBA led to the
      baseline enantioresolution of both drugs using 35 mM gamma-CD.

PMID- 18623281
TI  - Efficacy of glycoprotein enrichment by microscale lectin affinity chromatography.
AB  - Reproducible and efficient affinity enrichment is increasingly viewed as an
      essential step in many investigations leading to the discovery of new biomarkers.
      In this work, we have evaluated the repeatability of lectin enrichment of
      glycoproteins from human blood serum through both qualitative and quantitative
      proteomic approaches. In a comprehensive evaluation of lectin binding, we have
      performed 30 separate microscale lectin affinity chromatography experiments,
      followed by a conventional sample purification, and LC-MS/MS analysis of the
      enriched glycoproteins. Two lectin affinity matrixes, both with Con A lectin,
      immobilized to the same solid support but differing in the amount of immobilized
      lectin, were investigated to characterize their binding properties. Both
      qualitative and quantitative data indicate acceptable repeatability and binding
      efficiency for the lectin materials received from two different commercial
      sources.

PMID- 18623284
TI  - Synthesis and spectroscopic characterization of fluorescent blue-emitting
      ultrastable CdSe clusters.

PMID- 18623291
TI  - Application of metal-free triazole formation in the synthesis of cyclic RGD-DTPA
      conjugates.
AB  - The tandem 1,3-dipolar cycloaddition-retro-Diels-Alder (tandem crDA) reaction is
      presented as a versatile method for metal-free chemoselective conjugation of a
      DTPA radiolabel to N-delta-azido-cyclo(-Arg-Gly-Asp-d-Phe-Orn-) via
      oxanorbornadiene derivatives. To this end, the behavior of several
      trifluoromethyl-substituted oxanorbornadiene derivatives in the 1,3-dipolar
      cycloaddition was studied and optimized to give a clean and efficient method for
      bio-orthogonal ligation in an aqueous environment. After radioisotope treatment,
      the resulting 111In-labeled c(RGD)-CF3-triazole-DTPA conjugate was subjected to
      preliminary biological evaluation and showed high affinity for alpha(v)beta(3)
      (IC(50)=192 nM) and favorable pharmacokinetics.

PMID- 18623293
TI  - TEM-based metrology for HfO2 layers and nanotubes formed in anodic aluminum oxide
      nanopore structures.
AB  - Nanotubes are fabricated by atomic layer deposition (ALD) into nanopore arrays
      created by anodic aluminum oxide (AAO). A transmission electron microscopy (TEM)
      methodology is developed and applied to quantify the ALD conformality in the
      nanopores (thickness as a function of depth), and the results are compared to
      existing models for ALD conformality. ALD HfO2 nanotubes formed in AAO templates
      are released by dissolution of the Al2O3, transferred to a grid, and imaged by
      TEM. An algorithm is devised to automate the quantification of nanotube wall
      thickness as a function of position along the central axis of the nanotube, by
      using a cylindrical model for the nanotube. Diffusion-limited depletion occurs in
      the lower portion of the nanotubes and is characterized by a linear slope of
      decreasing thickness. Experimentally recorded slopes match well with two simple
      models of ALD within nanopores presented in the literature. The TEM analysis
      technique provides a method for the rapid analysis of such nanostructures in
      general, and is also a means to efficiently quantify ALD profiles in
      nanostructures for a variety of nanodevice applications.

PMID- 18623294
TI  - Is a highly ionic material still ionic as a nanoparticle?
AB  - The evolution of ionicity with size in highly ionic nanoparticles is investigated
      in small sesquioxide clusters. Representative clusters (Y2O3)N (N < 50) are
      theoretically analyzed by first-principle calculations within the density
      functional theory within the local-density approximation (DFT-LDA) framework and
      compared to experimental results obtained in an ultrahigh vacuum environment. By
      studying the structural relaxation and the electronic density of states as a
      function of size, the respective roles of ionicity and covalency are elucidated.
      For compounds as ionic as rare earth sesquioxides, the highly ionic bond
      essentially governs and preserves the crystalline structure. Particular attention
      is paid to the mechanism responsible for the surface relaxation. The role of the
      ions at the corners and edges appears prominent, especially in reducing the
      dipole carried by the particles. Eventually, contrary to the observations and
      computations concerning ionic surfaces, the mean ionicity remains constant as the
      size is reduced. It emphasizes that the description of highly ionic nanoparticles
      cannot be directly inferred from knowledge regarding the ionic surface
      reconstruction.

PMID- 18623296
TI  - Constructing carbon-nanotube/metal hybrid nanostructures using homogeneous TiO2
      as a spacer.

PMID- 18623297
TI  - Synthesis of homogeneous FePt nanoparticles using a nitrile ligand.

PMID- 18623295
TI  - Scalable routes to gold nanoshells with tunable sizes and response to near
      infrared pulsed-laser irradiation.
AB  - A simplified synthesis of hollow gold nanoshells 20-50 nm in diameter via the
      well-established templated galvanic replacement reaction of silver for gold is
      presented. The surface plasmon resonance absorbance of the nanoshells is tuned
      using basic colloid chemistry to control the size of the silver templates. The
      gold nanoshells have an aqueous core and are varied in size and shell thickness
      depending on the silver/gold reagent ratios. The template replacement chemistry
      is rapid, highly scalable, uses minimal amounts of toxic reagents, and in many
      cases is a true one-pot synthesis. The smallest nanoshells (20-nm diameter, 7-nm
      wall thickness) reach the highest temperature on irradiation with femtosecond
      light pulses in the near infrared and anneal to form spherical nanoparticles
      fastest, even though their plasmon resonance does not overlap as well as the
      larger nanoshells (50-nm diameter, 7-nm wall thickness) with 800-nm wavelength
      excitation.

PMID- 18623298
TI  - Controlling charge-carrier type in nanoscale junctions with linker chemistry.

PMID- 18623299
TI  - Silane nanopatterns via gas-phase soft lithography.

PMID- 18623300
TI  - Spin-crossover nanocrystals with magnetic, optical, and structural bistability
      near room temperature.

PMID- 18623303
TI  - Adhesion of mammalian cells to a recombinant attachment factor, CBD/RGD, analyzed
      by image analysis.
AB  - A luminance thresholding procedure was developed to quantify cell attachment of a
      variety of cell lines to CBD/RGD, a hybrid attachment factor comprising a
      cellulose binding domain and the fibronectin-like RGD attachment peptide. The
      technique used local thresholding, median filtering, and opening to separate and
      count cells on each image. Cell lines exhibited three different patterns of
      attachment to CBD/RGD, depending on whether it was immobilized on polystyrene or
      cellulose acetate. Vero, COS, HFF, 3T3, 293, and U373 cells attached well to
      CBD/RGD immobilized on polystyrene or cellulose acetate. CHO, MRC-5, and HEp-2
      cells attached to CBD/RGD immobilized on polystyrene, but not to CBD/RGD
      immobilized on cellulose acetate. BHK and L cells failed to attach to CBD/RGD
      immobilized on either polystyrene or cellulose acetate. The attachment of many
      cell lines to CBD/RGD was comparable with attachment of these cells to
      fibronectin. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623301
TI  - Synthesis and antimicrobial evaluation of some novel 2-aminothiazole derivatives
      of 4-hydroxy-chromene-2-one.
AB  - Syntheses of 2-aminothiazole derivatives of 4-hydroxy-chromene-2-one 2c-10c are
      reported in this paper. These compounds 2c-10c were prepared from 3-(2
      bromoacetyl)-4-hydroxy-chromene-2-one 1 and corresponding thiourea derivatives 2b
      10b using Hantzsch reaction. The structures of all compounds were confirmed by IR
      and( 1)H-NMR spectroscopy and elemental analyses. The molecules 2c-10c were
      evaluated for in vitro antimicrobial activity against ten bacteria and twelve
      fungi. All tested compounds exhibited antibacterial and antifungal activity.

PMID- 18623304
TI  - Nitrite inhibition of denitrification by Pseudomonas fluorescens.
AB  - Using a pure culture of Pseudomonas fluorescens as a model system nitrite
      inhibition of denitrification was studies. A mineral media with acetate and
      nitrate as sole electron donor and acceptor, respectively, was used. Results
      obtained in continuous stirred-tank reactors (CSTR) operated at pH values between
      6.6 and 7.8 showed that growth inhibition depended only on the nitrite
      undissociated fraction concentration (nitrous acid). A mathematical model to
      describe this dependence is put forward. The maximum nitrous acid concentration
      compatible with cell growth and denitrification activity was found to be 66 mug
      N/L. Denitrification activity was partially associated with growth, as described
      by the Luedeking-Piret equation. However, when the freshly inoculated reactor was
      operated discontinuosly, nitrite accumulation caused growth uncoupling from
      denitrification activity. The authors suggest that these results can be
      interpreted considering that (a) nitrous acid acts as a proton uncoupler; and (b)
      cultures continuoulsy exposed to nitrous acid prevent the uncoupling effect but
      not the growth inhibition. Examination of the growth dependence on nitrite
      concentration at pH 7.0 showed that adapted cultures (grown on CSTR) are less
      sensitive to nitrous acid inhibition than the ones cultivated in batch. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623305
TI  - Modeling of an industrial alcohol fermentation and simuiation of the plant by a
      process simulator.
AB  - The aim of the present study was the development of a general simulation module
      for fermentation within the framework of existing chemical process simulators.
      This module has been applied to an industrial plant which produces ethanol from
      beet molasses and fresh beet juice by Saccharomyces cerevisiae. An unstructured
      mechanistic model has been developed with kinetic laws that are based on a
      chemically defined reaction scheme which satisfies stoichiometric constraints.
      This model can be applied to different culture conditions and takes into account
      secondary byproducts such as higher alcohols. These byproducts are of prime
      importance and need to be correctly estimated because a sequence of distillation
      columns follow the fermentor in the plant. Important measurement campaigns have
      been performed on the plant to validate the model. Plant operation has been
      successfully simulated using the same kinetic model for both continuous and fed
      batch modes of production. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623306
TI  - A cometabilic kinetics model incorporating enzyme inhbition, inactivation, and
      recovery: I. Model development, analysis, and testing.
AB  - Cometabolic biodegradation prcesses are important for bioremediation of hazardous
      waste sites. However, these proceeses are not well understood and have not been
      modeled thoroughly. Traditional Michaelis-Menten kinetics models often are used,
      but toxic effects and bacterial responses to toxicity may cause changes in enzyme
      levels, rendering such models inappropriate. In this article, a conceptual and
      mathematical model of cometabolic enzyme kinetics i described. Model derivation
      is based on enzyme/growth-substrate/nongrowth-substrate interaction and
      incorporates enzyme inhibition (caused by the presence of a cometabolic
      compound), inactivation (resulting from toxicity of a cometabolic product), and
      recovery (associated with bacterial synthesis of new enbzyme in response to
      inactivation). The mathematical model consists of a system of two, nonlinear
      ordinary differential equations that can be solved implicitly using numerical
      methods, providing estimates of model parameters. Model analysis shows that
      growth substraate adn nongrowth substrate oxidation rates are related by a
      dimensionless constant. Reliability of tehy model solution prcedure is verifiedl
      by abnalyzing data ses, containing random error, from simulated experimentss with
      trichhloroethyylene (TCE) degradation by ammonia-oxidizing bacterialunder various
      conditions. Estimation of the recovery rate contant is deterimined to be
      sensitive to intial TCE concentration. Model assumptions are evaluated in a
      companion article using data from TCE degradation experiments with
      amoniaoxidizing bacteria. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623307
TI  - A cometabolic kinetics model incoroporating enzyme inhibition, inactivation, and
      recovery: II. Trichloroethylene degradaation experiments.
AB  - A Cometabolism enzyme kinetics model has been presented which takes into account
      changes in bacterial activity associated with enzyme inhibitiion, inactivation,
      inactivation of enzyme resulting from product toxicty, and respondent synthesis
      of new enzyme. Although this process is inherently unsteady-state, the model
      assumes that cometabolic degradation of a compound exhibiting product toxicity
      can be modeled as pseudo-steady-staate under certain conditions. In its
      simplified from, the model also assumes that enzyme inactivation is directly
      propoertional to nongrawth substrate oxidation, and that recovery is directly
      proportionla to growth substrate oxidation. In part 1, model drivation,
      simplification, and analyses were described. In this articles, model assuptiions
      are tested by analyzing data from experiments exmining trichloroethylene (TCE)
      degradation by the ammoniaoxidizing baceterium Nitrosomonas europaea in a
      quasisteady-state bioreactor. Model solution results showed steady-state
      bioreactor. Model solution results showed TCE to be a competitive inhibitoer of
      ammonia oxidation, with TCE affinity for ammonia monooxygenase (AMO) being about
      four times greater than that of ammonia for the enzyme. Inhibition was
      independent fo TCE oxidation and occurred essentially instantly upon exposure to
      TCE. In contrast, inactivation of AMO occurred more gradually and was
      proportional to the rate and amount of TCE oxidized. Evaluation of other O(2)
      dependent enzymes and electron transport proteins suggested that TCE-related
      damage was predominantly confined to AMO. In response to inhibition and/or
      inactivation, bacterial recovery was initiated, even in the presence of TCE,
      implying that membranes adn protein synthesis systems were functioning. Analysis
      of data and comparison of model results showed the
      inhibition/inactivation/recovery concept to provide a reasonable basis for
      understandign the effects fo TCE on AMO function and bacterial response. The
      model assumptions were verified except tht questions remain regarding the
      factores controlling recovery and its role in the long term. (c) 1995 John Wiley
      & Sons, Inc.

PMID- 18623309
TI  - Altered physicochemical characteristics of polyethylene glycol linked beet stem
      oxalate oxidase.
AB  - Oxalate oxidase (EC 1.2.3.4), obtained from the beet stem, was covalently linked
      to polyethylene glycol (PEG). Compared with native enzyme, the modified oxalate
      oxidase exhibited decreased electrophoretic mobility, increased storage
      stability, higher thermal stability, and resistance to heavy metal inactivation
      and proteolytic digestion. The chemical modification of oxalate oxidase with PEG
      also brought about a marked shift in its optimal pH, from pH 4.5 to 6.5, without
      altering its Michaelis constant (K(m)) significantly. These acquired properties
      of the immobilized oxalate oxidase render it suitable for possible applications
      in clinical, nutritional, and medical fields. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623308
TI  - Selective separation of tryptic beta-casein peptides through ultrafiltration
      membranes: Influence of ionic interactions.
AB  - Peptide separation by selective membrane filtration has numerous potential
      applications such as production of peptides with biological activities or
      spectific enrichment in compounds acting as flavoring agents or as growth factors
      required by the fermentation industry. The retention of peptides arising from
      tryptic hdroysis of beta-casein using an M5 Carbosep membrane (molecular wieght
      cutoll = 10,000 D) has been studied. The peptides with known sequences were
      characterized by their molecular weight, isoelectric point, and hydrophobicity.
      Our experiments highlighted that their transmission involves mechanisms other
      than size exclusion as developed elsewhere. The effect of ionic interactions
      between peptides and membrance has been investgated by vrying pH, ionic strength
      of bulk, and electric potential of filtering material. The charge of both
      peptides and membrane plays an important role in the transmission, particularly
      with small size and high or lkow isoelectric point. Then, peptides with the same
      sign as the membrane have lower transmission than expected from the size xclusion
      model, whereas peptides with opposite sign have higher trnsmission than expected,
      and even higher than 1 with some of them. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623310
TI  - Detachment of biomass from suspended nongrowing spherical biofilms in airlift
      reactors.
AB  - In three-phase internal loop airlift reactors, the detachment of biomass from
      suspended biofilm pellets in the presence of bare carrier particles was
      investigated under nongrowth conditions. The detachment rate was dominated by
      collisions between bare carrier particles and biofilm pellets. The concentration
      of bare carrier particles and the carrier roughness strongly influenced the
      detachment rate. A change in flow regime from bubbling to slug flow considerably
      increased the detachment rate. Otherwise, the superficial gas velocity did not
      directly affect the detachment rate. The influence of particle size was not
      clear. The bottom clearance did not affect the detachment rate within the tested
      range. Other aspects of reactor geometry might be important. The main detachment
      processes were abrasion and breakage of biofilm pellets. During the detachment
      process, two phases could be distinguished. In the first phase the detachment was
      relatively high, and both breakage and abrasion of biofilm pellets occurred.
      During the second phase, breakage dominated and the detachment rate was lower.
      The two-phase behavior is explained by differences in strength between the inner
      and outer biofilm layers, possibly caused by variations in local growth rates
      during biofilm formation. Differences in growth history might also explain the
      various detachment rates observed with different biofilm batches. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623311
TI  - A reagentless amperometric electrode based on carbon paste, chemically modified
      with D-lactate dehydrogenase, NAD(+), and mediator containing polymer for D
      lactic acid analysis. I. Construction, composition, and characterization.
AB  - A reagentless carbon paste electrode was designed for D-lactic acid analysis in a
      flow injection system for the monitoring of the production of D-lactate in a
      batch fermentation. D-Lactate dehydrogenase, nicotinamide adenine dinucleotide
      (NAD(+)), a synthetic redox polymer containing covalently attached toluidine blue
      O as mediator, graphite powder, and paraffin oil were used for the construction
      of the modified carbon paste electrode. D-Lactate selectivity was indicated by
      insignificant responses from a variety of possible interfernces including L
      lactate. The electrodes gave a linear response in the range between 0.05 and 5 mM
      D-lactate, with a detecting limit of 30 muM, allowing a sample throughput of 20
      h(-1). Preliminary investigations were made by covering the electrode surface
      with electropolymerized membranes. Satisfactory stability was observed, indicated
      by a reproducibility of 3.3% relative standard deviation (RSD, n = 31), with a
      non-membrane-covered electrode for the analysis of D-lactate in fermentation
      broth. A long-term stability (230 broth samples) was proven, suggesting the
      electrodes to have a good potential for use in on-line monitoring of fermentation
      processes. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623312
TI  - A reagentless amperometric electrode based on carbon paste, chemically modified
      with D-lactate dehydrogenase, NAD(+), and mediator containing polymer for D
      lactic acid analysis. II. On-line monitoring of fermentation process.
AB  - The production of D-lactic acid by Lactobacillus delbrueckii (ATCC 9649) during
      fermentation was monitored on-line with a reagentless D-lactate dehydrogenase
      modified carbon paste electrode in a flow injection system integrated with a
      filtration sampling device. The time delay between sampling and detection was
      approximately 6 min. The use of an electropolymerized ortho-phenylenediamine
      membrane on the elctrode resulted in a very selective sensor response with
      acceptable stability and sensitivity. The D-lactate concentrations determined on
      line agreed well with those determined by a standard method, suggesting that this
      sensor system is suitable for on-line monitoring of fermentation processes. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623313
TI  - A strategy for construction of industrial strains of distiller's yeast.
AB  - A procedure was developed for construction of industrial strains of distiller's
      yeast (Saccharomyces cerevisiae). It includes several steps: construction of
      congenic genetically marked haploid strains of opposite mating types starting
      from an industrial strain of hybrid nature, integrative transformation of the
      above haploid strains with a DNA fragment containing an expression cassette
      responsible for new technological facilities, and hybridization of transformants
      and isolation of final industrial homozygous strains under experimental
      conditions simulating commercial fermentation processes. This strategy permits
      the generation of strains that have desirable characteristics of traditional
      races of distiller's yeast along with new technological facilities determined by
      the particular expression cassette. Using this procedure, we have constructed an
      industrial strain with improved amylolytic activity. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623314
TI  - A model that links growth and secondary metabolite production in plant cell
      suspension cultures.
AB  - Plant cell suspensions of grape cells (Vitis vinifera L. cv. Gamay Freaux) were
      grown in shake flasks operated both in the batch and semicontinuous mode. A
      mathematical model was developed to describe grape cell growth, sucrose uptake,
      and secondary metabolite (anthocyanin) production. Parameters were estimated from
      batch studies data. The model was able to predict results for semicontinuous
      experiments by only modifying the value of four of these parameters. The modified
      parameters (maximum specific rate of biomass production, maximum specific rate of
      substrate consumption for maintenance, maximum specific rate of anthocyanin
      production, and degradation constant of anthocyanins) were related to the
      kinetics rather than to the yield of the process. The model introduces the
      concept of primary and secondary metabolism substrate concentration-dependent
      competition for precursors. Further, the model was able to predict the evolution
      of the cell system when substrate is scarce, as the value of the different
      kinetic constants determines the portion of substrate that is used for biomass
      production, secondary metabolite production, and cell maintenance. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623316
TI  - Cartilage production by rabbit articular chondrocytes on polyglycolic acid
      scaffolds in a closed bioreactor system.
AB  - Rabbit articular chondrocytes were seeded onto three-dimensional polyglycolic
      acid (PGA) scaffolds and placed into a closed bioreactor system. After 4 weeks of
      growth, meshes were examined for cartilage formation. Gross examination revealed
      solid, glistening material that had the appearance of cartilaginous tissue.
      Histologic examination revealed cell growth and deposition of extracellular
      matrix throughout the mesh with a less dense central core. Alcian blue and
      Safranin 0 staining showed deposition of glycosaminoglycans (GAGs).
      Immunostaining showed positive reactivity for type II collagen and chondroitin
      sulfate and no reactivity for type I collagen. Biochemical analysis showed
      collagen and GAG values to be 15% and 25% dry weight, respectively. Our results
      indicate that this type of system compares well with those previously described
      and should be useful for producing cartilage for evaluation in a clinical
      setting. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623317
TI  - Cultivation of cell-polymer tissue constructs in simulated microgravity.
AB  - Tissue-engineered cartilage was cultivated under conditions of simulated
      microgravity using rotating bioreactors. Rotation randomized the effects of
      gravity on inoculated cells (chondrocytes) and permitted their attachment to
      three-dimensional (3D) synthetic, biodegradable polymer scaffolds that were
      freely suspended within the vessel. After 1 week of cultivation, the cells
      regenerated a cartilaginous extracellular matrix (ECM) consisting of
      glycosaminoglycan (GAG) and collagen types I and II. Tissue constructs grown in
      simulated microgravity had higher GAG contents and thinner outer capsules than
      control constructs grown in turbulent spinner flasks. Two fluid dynamic regimes
      of simulated microgravity were identified, depending on the vessel rotation
      speed: (i) a settling regime in which the constructs were maintained in a state
      of continuous free-fall close to a stationary point within the vessel and (ii) an
      orbiting regime in which the constructs orbited around the vessel spin axis. In
      the settling regime, the numerically calculated relative fluid-construct velocity
      was comparable to the experimentally measured construct settling velocity (2-3
      cm/s). A simple mathematical model was used in conjunction with measured
      construct physical properties to determine the hydrodynamic drag force and to
      estimate the hydrodynamic stress at the construct surface (1.5 dyn/cm(2)).
      Rotating bioreactors thus provide a powerful research tool for cultivating tissue
      engineered cartilage and studying 3D tissue morphogenesis under well-defined
      fluid dynamic conditions. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623318
TI  - A kinetic model for product formation of microbial and mammalian cells.
AB  - Growth of microbial and mammalian cells can be classified into substrate-limited
      and substrate-sufficient growth according to the relative availability of the
      substrate (carbon and energy source) and other nutrients. It has been observed
      for a number of microbial and mammalian cells that the consumption rate of
      substrate and energy (ATP) is generally higher under substratesufficient
      conditions than under substrate limitation. Accordingly, the product formation
      under substrate excess often exhibits different patterns from those under
      substrate limitation. The extent of increase or decrease in product formation may
      depend not only on the nature of limitation and cell growth rate but also on the
      residual substrate concentration in a relatively wide range. The product
      formation kinetic models existing in literature cannot describe these effects. In
      this study, the Luedeking-Piret kinetic is extended to include a term describing
      the effect of residual substrate concentration. The extended model has a similar
      structure to the kinetic model for substrate and energy consumption rate recently
      proposed by Zeng and Deckwer. The applicability of the extended model is
      demonstrated with three microbial cultures for the production of primary
      metabolites and three hybridoma cell cultures for the production of ammonia and
      lactic acid over a wide range of substrate concentration. The model describes the
      product formation in all these cultures satisfactorily. Using this model, the
      range of residual substrate concentration, in which the product formation is
      affected, can be quantitatively assessed. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623319
TI  - Citric acid production by Candida lipolytica Y 1095 in cell recycle and fed-batch
      fermentors.
AB  - The effect of dissolved oxygen on citric acid production and oxygen uptake by
      Candida lipolytica Y 1095 was evaluated in cell recycle and fed-batch
      fermentation systems. The maximum observed volumetric productivity, which
      occurred at a dilution rate of 0.06 h(-1), a dissolved oxygen concentration of
      80%, and a biomass concentration of 5% w/v, in the cell recycle system, was 1.32
      g citric acid/L . h. At these same conditions, the citric acid yield was 0.65 g/g
      and the specific citric acid productivity was 24.9 mg citric acid/g cell . h. In
      the cell recycle system, citric acid yields ranged from 0.45 to 0.72 g/g. Both
      the volumetric and specific citric acid productivities were dependent on the
      dilution rate and the concentration of dissolved oxygen in the fermentor. Similar
      productivities (1.29 g citric acid/L . h) were obtained in the fed-batch system
      operated at a cycle time of 36 h, a dissolved oxygen concentration of 80%, and 60
      g total biomass. Citric acid yields in the fed-batch fermentor were consistently
      lower than those obtained in the cell recycle system and ranged from 0.40 to 0.59
      g/g. Although citric acid yields in the fed-batch fermentor were lower than those
      obtained in the cell recycle system, higher citric:isocitric acid ratios were
      obtained in the fed-batch fermentor. As in the cell recycle system, both the
      volumetric and specific citric acid productivities in the fed-batch fermentor
      were dependent on the cycle time and dissolved oxygen concentration. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623320
TI  - Propane-Induced biodegradation of vapor phase trichoroethylene.
AB  - Microbial degradation of trichloroethylene (TCE) has been demonstrated under
      aerobic conditions with propane. The primary objective of this research was to
      evaluate the feasibility of introducing a vapor phase form of TCE in the presence
      of propane to batch bioreactors containing a liquid phase suspension of
      Mycobacterium vaccae JOB5 to accomplish degradation. The reactor system consisted
      of three phases: a vapor phase introducing air, propane, and TCE; a liquid phase
      of the microbial suspension; and a solid phase in the form of the microorganisms.
      Long-term and initial rate experiments were conducted on three culture sets to
      evaluate microbial response. In two long-term test fed propane and approximately
      0.1 mg/L and 1 mg/L of TCE, respectively, propane utilization was more efficient
      at the high TCE concentration (600 mmol propane/mmol TCE versus 11,900 mmol
      propane/mmol TCE), because the propane degradation rate was approximately the
      same for both tests (6.73 mg/L . h and 7.85 mg/L . h for the high and low tests).
      In addition, TCE utilization decreased after complete propane consumption.
      Initial rate tests on culture sets fed propane only revealed that cells with a
      history of exposure to a high concentration of TCE had the highest specific
      growth rate, but the lowest half-saturation constant (7.60e(-3) h(-1) and 0.10
      mg/L, respectively). Tests fed variable TCE concentrations (0.031 to 5.378 mg/L
      in the liquid phase) with no propane showed TCE depletion but no biomass growth.
      The tests revealed that the TCE removal increased as the TCE concentration
      increased, indicating a greater removal efficiency at the higher concentrations.
      Tests with a constant initial propane concentration and variable liquid phase TCE
      concentration revealed that specific propane utilization was essentially the
      same. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623321
TI  - Effect of the concentration of DODMAC and 1-decanol on the behavior of reverse
      micelles in the extraction of amino acids.
AB  - The concentrations of dioctyldimethyl ammonium chloride (DODMAC) and 1-decanol in
      isooctane needed to form reverse micelles by phase contact have been determined.
      The behavior of these reverse micelles in the extraction of aspartic acid,
      glutamic acid, and threonine was studied by analyzing all of the ionic species in
      the aqueous phase. The amino acid is extracted from the aqueous phase by
      exchanging with the Cl(-) counterions of DODMAC in the reverse micelles. The
      ionic species in the reverse micelles tend toward their undissociated states as
      the water uptake by the reverse micelles decreases. The effect of 1-decanol on
      the extraction of the amino acids with two negative charges is due to the change
      in the water uptake of the reverse micelles. The concentration of DODMAC has no
      effect on the ion exchange of the amino acid with one negative charge with the
      Cl(-) counterions of DODMAC in the reverse micelles. Higher molar ratios of
      decanol to DODMAC favor the selective separation of amino acids with different
      charge numbers. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623322
TI  - Hydrodynamic effects on BHK cells grown as suspended natural aggregates.
AB  - Baby hamster kidney (BHK) cell aggregates grown in stirred vessels with different
      working volumes and impeller sizes were characterized. Using batch cultures, the
      range of agitation rates studied (25-100 rpm) led to aggregates with maximum
      sizes of 150 mum. Necrotic centers were not observed and cell specific
      productivity was independent of aggregate size. High cell viability was found for
      both single and adherent cells without an increase in cell death when agitation
      rate was increased. The increase in agitation rate affected aggregates by
      reducing their size and increasing their concentration and cell concentration in
      aggregates, while increasing the fraction of free cells in suspension. The
      experimental relationship between aggregate size and power dissipation rate per
      unit of mass was close to -1/4, suggesting a correlation with a critical
      turbulence microscale; this was independent of vessel scale and impeller geometry
      over the range investigated. Viscous stresses in the viscous dissipation subrange
      (below Kolmogoroff eddies) appear to be responsible for aggregate breakage. Under
      intense agitation BHK cells grown in the absence of microcarriers existed as
      aggregates without cell damage, whereas cells grown on the surface of
      microcarriers were largely reduced. This is a clear advantage for scaleup
      purposes if aggregates are used as a natural immobilization system in stirred
      vessels. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623323
TI  - Pathway engineering for production of aromatics in Escherichia coli: Confirmation
      of stoichiometric analysis by independent modulation of AroG, TktA, and Pps
      activities.
AB  - The synthesis of 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) is the first
      commitment of resources toward aromatics production in Escherichia coli. DAHP is
      produced during a condensation reaction between phosphoenolpyruvate (PEP) and
      erythrose 4-phosphate (E4P) catalyzed by DAHP synthases (coded by aroF, aroG, and
      aroH). Stoichiometric analysis has shown a severe PEP limitation in the
      theoretical yield of DAHP production from glucose due to the phosphotransferase
      system (PTS) for sugar uptake. This limitation can be relieved by (i) the
      recycling of pyruvate from PEP using PEP synthase (Pps) or (ii) use of non-PTS
      sugars such as xylose. Previous studies have shown the usefulness of
      overexpressing tktA (encoding transketolase), aroG, and pps (PEP synthase) for
      DAHP production in an aroB strain unable to utilize DAHP further. In the present
      study we confirm the predictions of the stoichiometric analysis by introducing
      pps, tktA, and aroG into vectors under independently controlled promoters. In
      glucose medium, although TktA has some positive effect on the final DAHP
      concentration, it has no effect on the yield (percent conversion). With Pps
      overexpression, the DAHP concentration produced from glucose is increased almost
      twofold and the yield is approaching the theoretical maximum, as predicted by the
      stoichiometric analysis. However, this Pps effect is observed only in the
      presence of both increased AroG and TktA. In xylose mimimal medium, the final
      DAHP concentration and the yield are completely determined by the AroG activity.
      TktA and Pps play no or insignificant roles, and the yield can reach the
      theoretical maximum without overexpression of these two enzymes. The results
      shown here are important for both rational design of metabolic pathways and
      industrial production of aromatics such as tryptophan, phenylalanine, indigo,
      quinic acid, and catechol.

PMID- 18623324
TI  - Monitoring of Saccharomyces cerevisiae in commercial bakers' yeast fermentation.
AB  - In the highly competitive market of commercial bakers' yeast, fermentations are
      operated for maximum efficiency and minimum production cost. In order to maintain
      competitiveness, the fermentations must be highly consistent with minimum
      variation in yeast performance, maximum yield on raw materials, and minimum
      production of undesirable side products. The use of advanced instrumentation is
      of critical importance to achieving these goals by the production engineer. An in
      situ optical density probe was used to determine the yeast cell density in full
      scale commercial bakers' yeast fermentations. The optical density probe results
      were compared with oxygen uptake rate analyses, packed cell volume, and off-line
      measured cell dry weights. The most accurate measurement of cell density was
      found to be the optical density probe. This instrument allowed the on-line
      determination of cell density with highly consistent results from fermentation
      batch to batch and with out the need for intermittent recalibration. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623325
TI  - Protein extration from an aqueous phase into a reversed micellar phase: Effect of
      water content and reversed micellar composition.
AB  - In the system composed of the cationic surfactant TOMAC (10 mM), the nonionic
      (co)surfactant Rewopal HV5 (2 mM), and octanol (0.1% v/v) in isooctane, reversed
      micelles are formed upon contact with an aqueous phase containing 50 mM ethylene
      diamine. alpha-Amylase can be transferred from the aqueous phase into reversed
      micelles in the pH range 9.5 to 10.5 and re-extracted into a second aqueous phase
      of different composition. The size of the reversed micelles (as reflected in the
      water content of the organic phase) can be varied by changes in percentage of
      octanol, type of counterion in the aqueous phase, or in the number of ethoxylate
      head groups of the nonionic surfactant. An increase in size results in transfer
      at lower pH values. Experiments in which the charge density in the reversed
      micellar interface was changed by incorporation of charged derivatives of the
      nonionic surfactant, without influencing the water content, revealed that an
      increased charge density facilitated transfer, resulting in a broader transfer
      profile. Replacement of TOMAC by other quaternary ammonium surfactants differing
      in number and length of tails revealed that, of the 14 surfactants tested, only 2
      gave appreciable amounts of transfer. The amount of transfer is related to the
      dynamics of phase separation of the surfactants: those giving a poor phase
      separation inactivate the enzyme. This inactivation is caused by electrostatic
      interactions between the charged surfactant head groups and charged groups on the
      enzyme. Electrostatic interactions are the first step of transfer, and can result
      in either incorporation in a reversed micelle, or, if reversed micelle formation
      is slow, in enzyme inactivation. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623326
TI  - Determination of the volumetric mass transfer coefficient (k(L)a) using the
      dynamic "gas out-gas in" method: Analysis of errors caused by dissolved oxygen
      probes.
AB  - There are many dynamic methods for measuring the volumetric mass transfer
      coefficient. The "gas out-gas in" method can directly determine the volumetric
      mass transfer coefficient in a bioreactor system and provide estimates of the
      volumetric microbial oxygen uptake rate and the average oxygen saturation
      concentration at the gas-liquid interface. The errors on these parameters are
      large if the dissolved oxygen probe response time is not considered. For reliable
      measurements, deconvolution of the oxygen probe measurements must be made. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623327
TI  - Removal of water produced from lipase-catalyzed esterification in organic solvent
      by pervaporation.
AB  - Esterification of oleic acid with n-butanol in the presence of Lipozyme(R) was
      carried out at 25 degrees C in isooctane with various initial water activities.
      Initial reaction rate as well as equilibrium conversion decreased at high initial
      water activity. Therefore, removal of water present in the reaction mixtures was
      essential. A pervaporation process was applied to the lipase-catalyzed synthesis
      of n-butyloleate to remove water. Pervaporation selectively separated water from
      the reaction mixture using a nonporous polymeric membrane, cellulose acetate.
      Therefore, pervaporation is potentially applicable to remove the water produced
      from various enzymatic processes, such as synthesis of various esters, peptides,
      and glycosides in a solvent system as well as in a solvent-free system. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623328
TI  - Simultaneous production of H(2) and O(2) in closed vessels by marine
      Cyanobacterium anabaena sp. TU37-1 under high-cell-density conditions.
AB  - A marine cyanobacterium, Anabaena sp. TU37-1, exhibited stable production of
      hydrogen and oxygen in closed vessels. About 8.4 and 4.3 mL (at atmospheric
      pressure) of hydrogen and oxygen accumulated, respectively, in flasks with 20 mL
      gas phase during 48 h incubation. Thus, concentration of H(2) and O(2) became 26
      and 13% of the gas phase, respectively. Duration of hydrogen production was
      prolonged by the periodic gas replacement in the reaction vessel. The conversion
      efficiencies of photosynthetically active radiation (fluorescent light, 22
      W/m(2)) to hydrogen were 2.4 and 2.2% during the initial 12- and 24-h incubation
      periods, respectively. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623330
TI  - Fluorophore-labeled carbohydrate analysis of immunoglobulin fusion proteins:
      Correlation of oligosaccharide content with in vivo clearance profile.
AB  - CTLA4 is a membrane receptor on cytotoxic T cells whose interaction with the B7
      counterreceptor on B cells is important in alloantigen responses. Soluble
      recombinant human and murine CTLA4 were produced using either Chinese hamster
      ovary or NS-0 cell lines. Expression vectors were constructed containing the gene
      coding for the extracellular domain of CTLA4 fused to either human lgG1 hinge,
      CH2, and CH3 domains or murine lgG2a hinge, CH2, and CH3 domain genes. These
      glycoproteins were produced in hollow-fiber or packed-bed-type bioreactors and
      purified from conditioned media by protein A affinity chromatography. Batches of
      purified CTLA4lg were analyzed for size, composition, and isoelectric point (pl)
      patterns by standard protein methods; oligosaccharide and monosaccharide profiles
      using several carbohydrate specific techniques; and in vivo clearance profiles
      using a murine model. Significant differences were observed between lots in their
      pl, clearance, and crbohydrate profiles. Higher overall pl values correlated with
      accelerated alpha-phase clearance and changes in oligosaccharide composition as
      determined by lectin binding analysis and electrophoresis of fluorophore
      conjugated carbohydrates. Preparations exhibiting slower clearance profiles had
      oligosaccharides with higher quantities of N-acetylneuraminic acid and were
      predominantly of an N-linked biantennary complex-type. Conversely, batches with
      accelerated clearance profiles had less detectable N-acetylneuraminic acid.
      Oligosaccharides from murine CTLA4lg produced in NS-0 cells had terminal N
      glycolylneuraminic acid but no detectable N-acetylneuraminic acid and had
      concomitant accelerated clearance. These data suggest that the presence and
      quantity of N-acetylneuraminic acid is an important component in predicting
      CTLA4lg plasma clearance rates and that production lots can be analyzed for
      oligosaccharide heterogeneity and sialic acid content by electrophoresis of
      fluorophore-conjugated carbohydrates. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623331
TI  - Influence of operating variables on liquid circulation in a 10.5-m(3) jet loop
      bioreactor.
AB  - A 10.5-m(3) concentric tube jet loop reactor was used to study the influence of
      the working liquid volume, mean superficial air velocity, operating pressure,
      downcomer aeration, liquid jet velocity, and two ratios of draft tube/reactor
      diameter (D(t)/D) on liquid circulation time (T(c)). The experiments were carried
      out in a water-air system with the use of the acid pulse method. Results showed
      that circulation time was independent of the working liquid volume over a certain
      minimum liquid level, whereas downcomer aeration and D(t)/D ratio appeared as
      amenable parameters to achieve a high degree of control over liquid circulation
      and mixing efficiency, and to optimize the overall reactor performance.
      Increasing the operating pressure caused a reduction of the liquid circulation
      rate. However, ionger residence times of the air bubbles and the higher mass
      transfer driving force that result at higher pressures improve oxygen
      utilization. The relationship between T(c) and air load was independent of the
      operating pressure, provided the correlation is given as a function of the mean
      superficial air velocity. Neither liquid circulation nor gas holdup were
      significantly affected by liquid jet velocity. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623332
TI  - An experimental study on a beta-cyclodextrin carbonate membrane reactor in PNPA
      hydrolysis.
AB  - Flat sheet membranes made of polyetheretherketone, known as PEEK-WC, and O
      octyloxycarbonyl beta-cyclodextrins were prepared by the phase inversion method.
      The cyclodextrins were entrapped in the polymeric membranes easily and simply in
      a single operation. Such functionalized membranes were tested for their catalytic
      activity. PNPA hydrolysis in a cyclodextrin membrane reactor was carried out as a
      model reaction. A significant improvement of reaction rate in comparison with the
      batch hydroxide ions catalyzed reaction was observed. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623333
TI  - Preparation of immobilized enzyme with high activity using affinity tag based on
      proteins A and G.
AB  - Affinity tag AG consisting of immunoglobulin G (lgG)-binding domains of protein A
      from Staphylococcus aureus (EDABC) and those of protein G from Streptococcus
      strain G148 (C2C3) were used to facilitate immobilization of beta-galactosidase
      (betagal) from Escherichia coli. Poly(methylmethacrylate/N
      isopropylacrylamide/methacrylic acid) [P(MMA/NIPAM/MAA)] and poly(styrene/N
      isopropylacrylamide/methacrylic acid) [P(St/NIPAM/MAA)] latex particles, which
      show thermosensitivity, were used as support materals to prepare affinity
      adsorbents. Human gamma-globulin (HgammaGb), whose major fraction is lgG, was
      used as an affinity ligand and was covalently immobilized onto the both latex
      particles by the carbodiimide method under various conditions. A fusion protein,
      AGbetagal, was immobilized at pH 7.3 by the specific binding of affinity tag to
      these affinity adsorbents. The amount of adsorbed AGbetagal per unit amount of
      immobilized HgammaGb, namely, efficiency of ligand utilization, was strongly
      affected by the type of latex particles and pH value for HgammaGb immobilization.
      The efficiency of ligand utilization was maximum in the affinity adsorbents
      prepared at pH 6.0 to 7.0, and that in the HgammaGb-P(MMA/NIPAM/MAA) latex
      particles was high. This result could be explained by the conformation and
      orientation of immobilized HgammaGb molecules. Immobilized AGbetagal retained
      approximately 75% of its activity in solution and the binding is stable enough to
      allow repeated use. These results clearly demonstrate that combination of the
      affinity tag AG and the affinity adsorbents, based on the thermosensitive latex
      particles, offers a simple and widely applicable method for preparation of
      immobilized enzyme with high activity. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623334
TI  - Effects of subzero temperatures on the kinetics of protease catalyzed dipeptide
      synthesis in organic media.
AB  - A depeptide synthesis was drastically influenced by the reaction temperature, in
      the range from -30 degrees to 25 degrees C. This article shows the kinetic
      reasons of this effect. alpha-Chymotrypsin was immobilized on celite and used in
      four different water-miscible solvents containing small amounts of water-miscible
      solvents containing small amounts of water. The reaction studied was the
      aminolysis of N-acetyl-L-phenylalanine ethyl ester (Ac-PheOEt) with L-alaninamide
      (Ala-NH(2)) and water for the acylenzyme complex, the nucleophile was favoured by
      low reaction temperatures. This effect (quantified as p-values) was observed in
      all four solvents, and it was greatest in acetonitrile and tetrahydrofuran. The
      esterase and amidase activities of the enzyme were studies using AcPheOEt and N
      acetyl-L-phenylalanyl-L-ananinamide (AcPheAla-NH(2)) as substrates. The Michaelis
      Menten parameters, K(m,app) and V(max), were determined for ester hydrolysis and
      dipeptide hydrolysis. Both K(m,app) and V(max) tended to increase with increasing
      temperature. Secondary hydrolysis was reduced at subzero temperatures because
      ester hydrolysis was favoured in relation to depeptide hydrolysis. Depeptide
      synthesis was thus favored by low temperatures in two ways: first, in the
      competition between the nucleophile and water for the acyl enzyme; and, second,
      in the competition between the ester substrate and the peptide substrate for the
      free enzyme. As a result, in acetonitrile containing 10% water, the maximal yield
      was 99% at -20%C compared with 84% at 25 degrees C. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623335
TI  - Optimum autoregulator addition strategy for maximum virginiamycin production in
      batch culture of Streptomyces virginiae.
AB  - Virginiae butanolides (VBs) are autoregulators of Streptomyces virginiae, which
      induce virginiamycin biosynthesis. Generally, autoregulators are synthesized by
      the microorganism itself during culture. Addition of chemically synthesized
      virginiae butanolide-C (VB-C), which is one of the VBs, can also control the
      induction time and the amount of virginiamycin production. The optimum
      concentration and shot-feeding time of VB-C for the maximum production of
      virginiamycins M and S were investigated in flasks and jar-fermentor batch
      cultures. VB-C addition later than 8 h from the start of culture induced not only
      virginiamycin M and S synthesis but also VB synthesis. Virginiamycin M and S
      production increased with the decrease of total VBs (produced VBs and added VB-C)
      concentration. That is, although VBs are needed to induce virginiamycin M and S
      synthesis, the amount of VB-C added should be such that as small an amount as
      possible of VBs is synthesized to achieve the maximum production of
      virginiamycins M and S. However, the VB-C addition earlier than 8 h from the
      start of culture showed no clear relationship between the amounts of VBs and
      virginiamycins M and S produced. In conclusion, the maximum production of
      virginiamycins M and S was attained by the shot addition of 5 mug/L VB-C at 8 h
      from the start of culture. The maximum value was about twofold that without VB-C
      addition. The optimum addition strategy of VB-C was confirmed by the jar
      fermentor experiments. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623336
TI  - Influence of electrostatic interactions on partitioning in aqueous polyethylene
      glycol/dextran biphasic systems: Part I.
AB  - To study the influence of charges on the partition of solutes in aqueous two
      phase systems of polyethylene glycol and dextran, partition coefficients of
      dimethylaminoethyl-dextran, trimethylamino-dextran, and bis (alpha,omega)-amino
      poly(ethylene glycol) were determined as a function of pH (range 2 to 12) and
      ionic strength. These polymers are derivatives of the phase forming components
      and carry ionizable groups that are charged or uncharged depending on the pH.
      Unexpectedly, the largest differences in the partition coefficients were found at
      high pH, where the modified polymers are uncharged. In addition, the partitioning
      of low-molecular-weight model compounds, ethylenediamine and iminodiacetic acid,
      as well as poly-L-lysine and poly(allylamine) was analyzed. A consistent pattern
      was observed in the partition of polyelectrolytes reflecting the influence of
      charge, but another property of aqueous phase systems unrelated to charge and
      changing with pH seems to be superimposed. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623337
TI  - Measuring enzyme hydration in nonpolar organic solvents using NMR.
AB  - A very sensitive NMR method has been developed for measuring deuterated water
      bound to proteins suspended in nonpolar solvents. This has been used to determine
      the amount of bound water as a function of water activity for subtilisin
      Carlsberg suspended in hexane, benzene, and toluene and for alpha-chymotrypsin in
      hexane. The adsorption isotherms for subtilisin in the three solvents are very
      similar showing that water activity can be usefully employed to predict the
      amount of water bound to proteins in nonpolar organic media. Comparison of the
      degree of enzyme hydration reached in nonpolar solvents with that obtained in air
      shows that adsorption of strongly bound water is hardly affected by the low
      dielectric medium, but adsorption of loosely bound water is significantly
      reduced. This suggests that the hydrophobic regions of the protein surface are
      preferentially solvated by solvent molecules, and that in a nonpolar environment
      formation of a complete monolayer of water over the protein surface is
      thermodynamically unfavorable. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623338
TI  - The viability of Scenedesmus bicellularis cells immobilized on alginate screens
      following nutrient starvation in air at 100% relative humidity.
AB  - The viability of algal cells immobilized on screens and starved in a water
      saturated air stream was studied at the laboratory scale. This new process for
      wastewater biotreatment has been developed using immobilized cells, which were
      starved in air, to obtain a high rate of nutrient removal. A unicellular green
      microalgae, Scenedesmus bicellularis, was isolated from secondary decantation
      tanks at an urban wastewater treatment plant and grown in a synthetic medium for
      12 days. The cells were then concentrated by centrifugation and immobilized on
      alginate screens. The screens were then inserted in a photochamber saturated at
      100% relative humidity and subjected to a photoperiod of 16 h in the light and 8
      h in the dark, with an illumination of 150 muE m(-2) s(-1) provided by
      fluorescent lamps. After 48 h of nutrient starvation, the immobilized cells were
      used for the removal of ammonium and orthophosphate from a synthetic secondary
      wastewater effluent in a plexiglass reactor. During the sequential operation of
      starvation followed by incubation in the presence of nutrients, fast growth of
      viable cells in the gel matrix was obtained and there was no appreciable decay of
      chlorophyll a or cell activity. When these immobilized and starved cells were
      incubated in wastewater, ammonium (NH(4) (+)) and orthophosphate (PO(4) (3-))
      ions were quickly taken up from medium. After three successive 2-h exposures to
      wastewater, immobilized algal cells were freed by dissolving the Ca-alginate with
      phosphate as 0.2 M Na(3)PO(4) and resuspended in fresh culture medium. Results
      indicate that free cells transferred to rich medium remained viable, but the
      growth rate revealed that the viable cells decreased their culturability. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623339
TI  - Mass transfer and temperature effects on substrate utilization in brewery
      granules.
AB  - Liquid film and diffusional resistances of brewery granules during acetate,
      propionate, and ethanol utilization were investigated. Substrate utilization rate
      increased with decreased granule size. Effectiveness factors for acetate,
      propionate, and ethanol were calculated by comparing the maximum rates of
      substrate utilization of whole granules (1.8 to 3.0 mm) and fine flocs (20 to 75
      mum) derived by disrupting whole granules. For acetate, propionate, and ethanol,
      maximum specific substrate utilization rates (k(m') g/g VS . d) for the flocs,
      were 5.11, 6.25, and 5.49, respectively, and half-velocity coefficients (K(g')
      mM) were 0.45, 0.40, and 3.37, respectively. Calculated effectiveness factors
      were 0.32, 0.41, and 0.75 for acetate, propionate, and ethanol, respectively. The
      effect of temperature on substrate utilization was examined at 26 degrees C, 31
      degrees C, and 37 degrees C using acetate as sole carbon source. Utilization
      rates increased with temperature. Flocs were most sensitive to temperature, and
      whole granules were least affected. The behavior of flocs was well described by
      the Van't Hoff-Arrhenius equation. Effectiveness factors for acetate utilization
      by the granules were 0.36, 0.35, and 0.32 at 26 degrees C, 31 degrees C, and 37
      degrees C, respectively, indicating little effect of temperature. Based on these
      results, we conclude that both liquid film and diffusional resistances influenced
      the rate of substrate utilization in a UASB reactor with granular sludge.
      Temperature effects were much less important than diffusional limitations within
      the granules. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623340
TI  - Competition between nitrate and nitrite reduction in denitrification by
      Pseudomonas fluorescens.
AB  - A pure culture of Pseudomonas fluorescens was used as a model system to study the
      kinetics of denitrification. An exponentially growing culture was harvested and
      resuspended in an anoxic acetate solution buffered with K/Na phosphate at pH
      values of 6.6, 7.0, 7.4, and 7.8. The temperature was kept at 28 degrees C in all
      assays. Nitrate pulses of approximately 0.2 mg N/L caused nitrite to accumulate
      due to a faster rate of nitrate reduction over nitrite reduction. The rate of
      nitrate reduction was observed to depend on its concentration as predicted by the
      Michaelis-Menten equation. At nonlimiting nitrate concentrations, nitrite
      reduction was described by the same equation. Otherwise, nitrite reduction also
      depended on nitrate concentration. Consequently, nitrate and nitrite reductions
      compete with each other for the oxidation of common electron donors. A kinetic
      model for nitrate competitive inhibition of nitrite reduction is proposed. The
      model was used to interpret the nitrate and nitrite profiles observed at the four
      pH values: the optimum pH value was 7.0 in both cases; the affinity for nitrite
      was also not affected by the medium pH in the range of values 6.6 to 7.4
      (K(mNO(3) ) = 0.04 mg N/L); the affinity for nitrite was also not affected by the
      medium pH in the range of values 6.6 to 7.4 (K(mNO(2) ) = 0.06 mg N/L), but it
      decreased sharply for the pH value of 7.8. Although the ratio between the two
      maximum reduction rates (V(max NO(2) )/V(max NO(3) )) is constant, nitrite
      accumulation depends on the medium pH value. Therefore, the regulation mechanism
      that shifts the electron flow between the two terminal reductases is readily
      reversible and does not change their relative maximum reduction rates. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623341
TI  - A model of the binding, entry, uncoating, and RNA synthesis of Semliki Forest
      virus in baby hamster kidney (BHK-21) cells.
AB  - A quantitative understanding of viral trafficking would be useful in treating
      viral-mediated diseases, designing protocols for viral gene therapy, and
      optimizing heterologous protein production. In this article, a model for the
      trafficking of Semliki Forest virus and its RNA synthesis in baby hamster kidney
      (BHK-21) cells is presented. This model includes the various steps leading to
      infection such as attachment, endocytosis, and viral fusion in the endosome. The
      model estimates a mean fusion time of 4 to 6 min for the wild-type virus, and 38
      min for Fus-1, an SFV mutant which requires a lower pH for fusion. These mean
      fusion times are consistent with the time-scale of endosomal acidification,
      suggesting viruses fuse almost instantaneously with the endosomal membrane as
      soon as the pH of the endosome drops below the pH threshold of the virus.
      Infection is most likely controlled at the level of viral uncoating, as shown by
      the close agreement between the efficiency of uncoating and the experimentally
      determined fraction of viruses that is infectious. The viral RNA synthesized per
      cell is best described by assuming that it depends on the number of uncoated
      viruses prior to the onset of replication according to a saturation-type
      expression. A Poisson distribution is used to determine the distribution of
      uncoated viruses among the cells. Because attachment is the rate-limiting step in
      the uncoating of the virus, increasing the attachment rate can lead to enhanced
      RNA synthesis and, hence, new virion production. Such an increase in the
      attachment rate may be obtained by lowering the medium pH or the addition of a
      polycation. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623342
TI  - Effect of single nutrient limitation of poly-beta-hydroxybutyrate molecular
      weight distribution in alcaligens europhus.
AB  - The effect of magnesium and phosphate limitation on the molecular weight
      distribution of poly-beta-hydroxybutyrate (PHB) in Alcaligens europhus in
      cotinuons culture has been stuied. Conditions of nitrogen limitation both with
      glucose excess (above ca. 20 g/L) and without excess were investigated Under N
      limitation and glucose excess, M(w) decreases when the magnesium content is
      decreased below 50% (19.7 mg/L) of the basal medium content; this also results in
      a broadenng of molecular weight distribution (M(w)/M(n)) from 2 to 5 and a
      decrease in M(w) fron 2 x 10(6) to 0.9 x 10(6). Below 20% of the basal content of
      magnesium (7.9 mg/L) these two trends were reversed. This behaviour was not
      observed in the absence of glucose excess, phshate had virtually no effect on PHB
      M(w) or its distribution, whereas wih no (or little) glucose excess M(w) of the
      PHB decreased with phosphate concentrations below 50% of the basal level (0.705
      g/L). Hence, in continuous or fed-batch cultures, in addition to nitrogen
      limitation to alklow for PHB accumulation, it is necesary to control both the
      addition of glucose (no excess) and also to maintain magnesium limitation (ca.
      25% of basal medium level, 9.9 mg/L) and phosphate above 50% of he basal level
      (0.705 g/L). Thus, when broadening of molecular weight destribution (increase in
      M(w)/M(n)) is observed at the end of fed-batch culture it is probably caused by
      phosphate limitation and/or glucose excess. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623344
TI  - Polysulfone affinity membranes for the treatment of amino acid mixtures.
AB  - Affinity membranes for the treatment of solutions containing amino acids were
      obtained via lithiating polysulfone that was subsequently converted with
      glycidylether. From this polymer asymmetric ultrafiltration membranes were cast.
      The membranes were reacted with iminodiacetic acid yielding membranes fitted out
      with bidentate chelates. The same reaction path was applied to commercially
      available symmetric microfiltration membranes. The chelate-bearing membranes were
      complexed with Cu, Ni, and Zn ions. For the experiments with amino acids only the
      Cu-complexed membranes were used. The complexation constants for histidine and
      tryptophan for six different membranes were determined. Because of the affinity
      of these two amino acids for the complexed Cu ions, they could easily be
      separated from solutions containing amino acids such as alanine, glycine, and
      valine. Also, concentrating very dilute amino acid solutions was carried out
      successfully.

PMID- 18623345
TI  - Two-step immobilized enzyme conversion of cephalosporin C to 7
      aminocephalosporanic acid.
AB  - The first large-scale production of 7-aminocephalosporanic acid (7ACA) from
      cephalosporin C (CPC) using a wholly enzymatic synthesis method is reported here.
      We produced 7ACA from CPC in as high a molar yield as 85% using the immobilized
      enzymes D-amino acid oxidase (D-AOD) and glutaryl-7-ACA acylase (GL-acylase). In
      the first reactor, CPC is converted to keto-adipyl-7-aminocephalosporanic acid
      (keto-7ACA) using an immobilized D-AOD isolated from a yeast, Trigonopsis
      variabilis. The keto-7ACA is then spontaneously converted to glutaryl-7
      aminocephalosporanic acid (GL-7ACA) via a chemical reaction with hydrogen
      peroxide. The hydrogen peroxide is also a product of the D-AOD reaction. Near
      quantitative conversion of the keto-7ACA to GL-7ACA was observed. The second
      reactor converts GL-7ACA to 7ACA using an immobilized GL-acylase, which was
      isolated from a recombinant Escherichia coli. The final 7ACA crystalline product
      is a high quality product. The reactions are conducted under very mild aqueous
      conditions: pH 8.0 and 20 degrees to 25 degrees C. The production of desacetyl
      side products is minimal. This process is currently being implemented on an
      industrial scale to produce 7ACA.

PMID- 18623346
TI  - An autoclavable glucose biosensor for microbial fermentation monitoring and
      control.
AB  - The design, construction, and characterization of a prototype-regenerable glucose
      biosensor based on the reversible immobilization of glucose oxidase (GOx) using
      cellulose binding domain (CBD) technology is described. GOx, chemically linked to
      CBD, is immobilized by binding to a cellulose matrix on the sensor-indicating
      electode. Enzyme immobilization can be reversed by perfusing the cellulose matrix
      with a suitable eluting solution. An autocavable sensor membrane system is
      employed which is shown to be practical for use in real microbial fermentations.
      The prototype glucose biosensor was used without failure or deterioration during
      fed-batch fermentations of Escherichia coli reaching a maximum cell density of 85
      g (dry weight)/L. Medium glucose concentration based on sensor output correlated
      closely with off-line glucose analysis and was controlled manually at 0.44 +/-
      0.2 g/L for 2 h based on glucose sensor output. The sensor enzyme component could
      be eluted and replaced without interrupting the fermentation. To our knowledge,
      no other in situ biosensor has been used for such an extended period of time in
      such a high-cell-density fermentation.

PMID- 18623347
TI  - Intracellular responses of productive hybridomas subjected to high osmotic
      pressure.
AB  - It has previously been found that hybridoma cells under hyperosmotic stress
      produce higher amounts of antibody. This study identified the cellular processes
      and mechanisms that occur during this event. In studies of hybridomas adapted to
      osmolarities ranging between 300 and 450 mOsm (using NaCI), antibody production
      increased to a saturation level while cell growth decreased progressively. At 500
      mOsm, lower cell numbers and markedly decreased productivity resulted. Sucrose
      and KCI were found to induce similar trends, except to different extents. Several
      important changes in cellular responses were observed. Elevation of osmolarity
      with NaCl from 300 to 350 mOsm causes an increase of zwitterionic amino acid
      uptake, which occurred via Na+-dependent transport systems. In particular, system
      A was enhanced by 1.86-fold, but no enhancement was observed for Na+- independent
      transport systems. In addition, amino acids reactive with Na +-dependent
      transport systems were observed to be abundant within osmotically stressed
      hybridomas in the middle and late exponential stages. Sucrose and KCI caused
      similar uptake effects, but to a lesser degree, as long as sodium ions were
      present in solution. Specific consumption rates of glucose and glutamine increase
      by 19% and 20%. respectively, under high osmolarity treatment. These increases
      were confirmed by the 5% to 10% increase in cellular metabolic activity. At 350
      mOsm, growth rate was slower compared with the 300-mOsm culture, which was
      reflected by the lower DNA concentration. Stressed cultures contained enhanced
      levels of total RNA, of which -80% is ribosomal RNA (rRNA). Higher rRNA content
      could in turn increase the translation rates of proteins. This was reflected in
      the accumulation of both dry cell weight and total cellular protein at linear
      rates of 0.42 pg/106 cells/mOsm and 0.21 pg/106 cells/mOsm, respectively, with
      increasing osmolarity between 300 and 450 mOsm. Overall, hybridomas increased
      their metabolic activities and amino acids uptake via the Na+-dependent symports
      to compensate for the osmotically elevated external environment. These effects
      contribute directly and indirectly to the increased cell mass consisting of a
      larger pool of amino acids, RNA, cellular proteins, and secreted antibody product

PMID- 18623348
TI  - Effect of different cell culture conditions on the polypeptide integrity and N
      glycosylation of a recombinant model glycoprotein.
AB  - The effect of different short-term controlled cell culture conditions on the
      product quality of a genetically engineered human interleukin-2 N-glycosylation
      variant protein expressed from a baby hamster kidney cell line (BHK-21) has been
      investigated. A perfused 2-L stirred tank reactor was used. Products purified
      from the culture supernatant of cells grown under experimentally initiated
      nutrient limitations (glucose, amino acids, pO(2)) were characterized by their
      HPLC-elution profile, SDS-PAGE and western blotting, amino acid sequencing as
      well as for their N-linked carbohydrates, using "HPAEC-PAD fingerprinting" and
      methylation analysis. The glycoprotein products secreted from cells under the
      different culture conditions (kept for 24 h, after an adaption time period of 48
      h) showed an almost identical oligosaccharide pattern. By contrast, short-term
      changes of the culture condition led to considerable differences in the ratio of
      glycosylated to unglycosylated protein forms. Significant amounts of NH(2)
      terminally truncated polypeptide forms were observed. They lacked proponderantly
      the first two amino acids; however, under certain culture conditions forms
      lacking up to eight NH(2)-terminal amino acids were detected. (

PMID- 18623349
TI  - Conversion of native lignin to a highly phenolic functional polymer and its
      separation from lignocellulosics.
AB  - An original reaction system (the phase separative reaction system) has been
      designed for derivatizing native lignins to highly phenolic, functional polymers.
      This system is composed of a phenol derivative and concentrated acid, which are
      not miscible at room temperature. The key point of the lignin functionalization
      process, including the phase separative system, is that lignin and carbohydrates,
      which are totally different in structures and reactivities, are modified
      individually in the different phases: lignin is present in the organic phase and
      carbohydrates in the aqueous phase. Through the process, lignin was modified
      selectively at Calpha-positions of side chains, the most reactive sites, to give
      highly phenolic, light-colored, diphenylmethane-type materials which still
      retained original interunit linkages formed by the dehydrogenative polymerization
      during the biosynthesis. The carbohydrates were swollen, followed by partial
      hydrolysis and dissolution in the acid solution, resulting in the perfect
      decomposition of interpenetrating polymer network structures in the cell wall.
      Therefore, the functionalization of lignin and the separation of resulting lignin
      from carbohydrates were quickly achieved at room temperature, independent of wood
      species. This process would be a powerful tool for estimating structures and
      reactivities of lignins as well as the functionalization of lignins, because of
      the selective structural modifications.

PMID- 18623350
TI  - Biofilm parameters influencing biocide efficacy.
AB  - The influence of biofilm areal cell density, species composition, and the
      presence of abiotic particles on the disinfection and removal of bacterial
      biofilms by monochloramine was investigated. Mono- and binary population biofilms
      of Pseudomonas aeruginosa and Klebsiella pneumoniae were grown on stainless-steel
      slides in a continuous flow annular reactor. Biofilms were treated in the reactor
      with a pulse/step dose of 4 mg/L monochloramine for 2 h. Biofilm samples were
      disaggregated and assayed for colony formation on R2A agar and for total cell
      numbers by acridine orange direct counts. These data were used to determine
      apparent first order rate coefficients for the processes of disinfection and
      detachment. Disinfection rate coefficients exceeded detachment rate coefficients
      by as much as an order of magnitude and the two coefficients were poorly
      correlated (r = 0.272). The overall decay rate coefficient (disinfection plus
      detachment) depended strongly on the initial biofilm areal cell density. It
      displayed a parabolic dependence on cell density with a maximum near 10(8)
      cfu/cm(2). This result points to multiple factors influencing biofilm
      susceptibility to antimicrobial challenge. Decay rates of K. pneumoniae measured
      in binary population biofilms were comparable with those measured in
      monopopulation biofilms (p = 0.61). P. aeruginosa decayed more slowly in biofilm
      dominated by K. pneumoniae (p = 0.028), indicating some interaction between
      species. The presence of kaolin and calcium carbonate particles in the biofilm
      reduced disinfection efficacy.

PMID- 18623351
TI  - A mathematical model for the growth of mycelial pellet populations.
AB  - In liquid culture, filamentous organisms often grow in the form of pellets.
      Growth result in an increase in radius, whereas shear forces result in release of
      hyphal fragments which act as centers for further pellet growth and development.
      A previously published model for pellet growth of filamentous microorganisms has
      been examined and is found to be unstable for certain parameter values. This
      instability has been identified as being due to inaccuracies in estimating the
      numbers of fragments which seed the pellet population. A revised model has been
      formulated, based on similar premises, but adopting a finite element approach.
      This considers the population of pellets to be distributed in a range of size
      classes. Growth results in movement to classes of increasing pellet size, while
      fragments enter the smallest size class, from which they grow to form further
      pellets. The revised model is stable and predicts changes in the distribution of
      pellet sizes within a population growing in liquid batch culture. It considers
      pellet growth and death, with fragmentation providing new centers of growth
      within the pellet population, and predicts the effects of shear forces on pellet
      growth and size distribution. Predictions of pellet size distributions are tested
      using previously published data on the growth of fungal pellets and further
      predictions are generated which are suitable for experimental testing using
      cultures of filamentous fungi or actinomycetes.

PMID- 18623352
TI  - Physico-chemical properties of the encapsulation matrix and germination of carrot
      somatic embryos.
AB  - Carrot somatic embryos were encapsulated in alginate gel beads. To improve the
      quality of a "synthetic seed" coating, the rheology and dehydration properties of
      different matrices were tested. By increasing alginate and CaCl(2)
      concentrations, additional mineral elements were shown to increase resistance to
      rupture, and to depress the germination of somatic embryos. A polysaccharide
      addition was found to slow the alginate matrix dehydration; alginate-gellan gum
      and alginate-kaolin matrices could preserve the viability of somatic embryos at
      low relative humidities (30% to 35% germinations at 50% relative humidity) to a
      greater extent than other matrices.

PMID- 18623353
TI  - High viable cell concentration fed-batch cultures of hybridoma cells through on
      line nutrient feeding.
AB  - A hybridoma cell line was cultivated in fed-batch cultures using a low-protein,
      serum-free medium. On-line oxygen uptake rate (OUR) measurement was used to
      adjust the nutrient feeding rate based on glucose consumption, which was
      estimated on-line using the stoichiometric relations between glucose and oxygen
      consumption. Through on-line control of the nutrient feeding rate, not only
      sufficient were supplied for cell growth and antibody production, but also the
      concentrations of glucose and other important nutrients such as amino acids were
      maintained at low levels during the cell growth phase. During the cultivation,
      cell metabolism changed from high lactate production and low oxygen consumption
      to low lactate production and high oxygen consumption. As a result the
      accumulation of lactate was reduced and the growth phase was extended. In
      comparison with the batch cultures, in which cells reached a concentration of
      approximately 2 x 10(6) cells/mL, a very high concentration of 1.36 x 10(7)
      cells/mL with a high cell viability (>90%) was achieved in the fed-batch culture.
      By considering the consumption of glucose and amino acids, as well as the
      production of cell mass, metabolites, and antibodies, a well-closed material
      balance was established. Our results demonstrate the value of coupling on-line
      OUR measurement and the stoichiometric relations for dynamic nutrient feeding in
      high cell concentration fed batch cultures.

PMID- 18623354
TI  - Hyphal growth and fragmentation of Penicillium chrysogenum in submerged cultures.
AB  - A previously derived population model describing the average properties of hyphal
      elements in submerged cultures of filamentous fungi was revised, and a term for
      the influence fo spore germination on the average total hyphal length was added.
      The model was derived from a general balance for the distribution function for
      the hyphal elements. Based on experimental data and the derived model, simple
      kinetic expressions for spore germination, tip extension, branching, and hyphal
      break-up were set up. It is concluded that spore germination can be quantified by
      three parameters: (1) the time at which spore germination is initiated, (2) the
      time at which spore germination terminates, and (3) the fraction of viable spores
      in a spore suspension. The frequency of spore germination can be described with
      the B-distribution. For growth kinetics it is concluded that the branching
      frequency is closely correlated with the total hyphal length and that the average
      tip-extension rate can be described with saturation kinetics with respect to the
      hyphal length. Finally, the rate of fragmentation is linearly related to the
      energy input to the bioreactor, and related to the effective hyphal length.

PMID- 18623355
TI  - Process optimization and modeling of trichlorophenol degradation by Phanerochaete
      chrysosporium.
AB  - The biodegradation of 2,4,6-trichlorophenol and 2,4,5-trichlorophenol by the
      white rot fungus Phanerochaete chrysosporium was studied in batch and continuous
      reactor systems. Experiments were conducted in shake flasks as well as in packed
      bed reactors in which the fungus was immobilized. The degradation rates in the
      packed-bed reactors were found to be two orders of magnitude greater than those
      obtained in the shake flasks in which the fungus was just suspended. The
      degradation rate was found to be influenced by the concentrations of the carbon
      and nitrogen sources, pH, and fluid shear stress. Optimal ranges of these
      parameters to maximize biodegradation were determined. A mathematical model was
      developed in which the degradation process was assumed to consist of two
      sequential reaction steps, the first catalyzed by an extracellular enzyme system
      and the second requiring the presence of the mycelium. The deactivation of the
      extracellular enzyme system was also accounted for in the model. The Michaelis
      Menten and the enzyme deactivation parameters were determined independently. Good
      agreement between the experimental data and the results produced by the
      regression was found.

PMID- 18623356
TI  - Biocatalytic synthesis of acrylates in organic solvents and supercritical fluids:
      III. Does carbon dioxide covalently modify enzymes?
AB  - We have previously demonstrated that the activity of the lipase (Candida
      cylindracea) catalyzed transesterification reaction between methylmethacrylate
      and 2-ethylhexanol in supercritical carbon dioxide is comparatively low. In this
      article, we have investigated the same reaction in supercritical carbon dioxide
      with a special emphasis on determining the extent of any interaction between the
      enzyme and carbon dioxide. Transesterification reaction rates in hexane and
      supercritical carbon dioxide are compared at different temperatures. In
      supercritical carbon dioxide, temperature was found to have no significant effect
      on reaction rate in the range of 40 degrees to 55 degrees C. Above 55 degrees C,
      however, the reaction rate increased significantly as a function of temperature.
      It appears that carbon dioxide forms reversible complexes with the free amine
      groups on the surface of the enzyme. Direct evidence of modification was obtained
      using mass spectroscopy to detect the extent of modification of a pure protein.
      The kinetics of the reaction have been studied in hexane, and they obey a ping
      pong bi-bi mechanism with inhibition by 2-ethylhexanol. The effect of bubbling
      carbon dioxide and/or fluoroform on the reaction rate in hexane at different
      temperatures suggests that the enzyme undergoes shear inactivation in hexane. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623357
TI  - Preparation and in vitro analysis of microencapsulated genetically engineered E.
      coli DH5 cells for urea and ammonia removal.
AB  - This article describes a novel method of urea and ammonia removal using
      microencapsulated, genetically engineered Escherichia coli DH5 cells.
      Optimization of bacterial cell encapsulation was carried out. The optimal method
      consists of alginate 2.00% (w/v) at a flow rate of 0.0724 mL/min and a coaxial
      air flow rate of 2.00 L/min. This produces spherical, alginate-poly-L-lysine
      alginate (APA) microcapsules of an average 500 +/- 45 mum diameter. Increasing
      the concentration of alginate from 1.00% to 1.75% improves the quality of the
      microcapsules, while cell viability remains unaffected. The APA microcapsules are
      mechanically stable up to 210-rpm agitation with no bacterial cell leakage. The
      in vitro performance of urea and ammonia removal by encapsulated bacteria is
      assessed. One hundred milligrams of bacterial cells in APA microcapsules, in
      their log phase state of growth, can lower 87.89 +/- 2.25% of the plasma urea
      within 20 min and 99.99% in 30 min. The same amount of encapsulated bacteria can
      also lower ammonia from 975.14 +/- 70.15 muM/L to 81.151 +/- 7.37 muM/L in 30
      min. There are no significant differences in depletion profiles by free and
      encapsulated bacteria for urea and ammonia removal. This novel approach using
      microencapsulated, genetically engineered E. coli cells is significantly more
      efficient than presently available methods of urea and ammonia removal. For
      instance, it is 30 times more efficient than the standard urease-ammonium
      adsorbent system. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623358
TI  - Effects of temperature and cycloheximide on secretion of cloned invertase from
      recombinant Saccharomyces cerevisiae.
AB  - The effects of temperature on the kinetics and efficiency of secretion of cloned
      invertase were investigated in a recombinant yeast system. This system consisted
      of the baker's yeast Saccharomyces cerevisiae (SEY2102) transformed with the 2mu
      based plasmid pBR58 which contains the entire SUC2 gene including the promoter,
      signal sequence, and structural gene. The recombinant yeast produces the
      naturally secreted yeast enzyme invertase. In transition experiments done at
      temperatures ranging from 25 degrees to 45 degrees C, the maximum invertase level
      and secretion rate exhibited maxima of 5.5 U/mL . OD and 4.6 U/mL . OD per hour,
      respectively, at 35 degrees C. Experiments involving the use of cycloheximide
      showed that it took approximately 15 min for secreted invertase to move through
      the secretion pathway, which held 0.4 U/mL . OD of specific activity. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623359
TI  - Synthesis of aspartame precursor with an immobilized thermolysin in mixed organic
      solvents.
AB  - N-(benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester, a precursor of the
      synthetic sweetener, aspartame, was synthesized from N-(benzyloxycarbonyl)-L
      aspartic acid and L-phenylalanine methyl ester with an immobilized thermolysin
      (EC 3.4.24.4) in the mixed organic solvent system of tert-amyl alcohol and ethyl
      acetate. A mixed solvent consisting of tert-amyl alcohol and ethyl acetate at a
      ratio of 33:67 (v/v) was found to be the most suitable with respect to synthetic
      rate and stability of the immobilized enzyme. The reaction continued to proceed
      quite successfully in a column reactor at 40 degrees C and at a space velocity of
      3.6 h(-1) with a yield of 99%, using 40 mM Z-Asp and 200 mM PheOMe dissolved in
      the mixed solvent as the substrate. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623361
TI  - Kinetics and mass transfer for lactic acid recovered with anion exchange method
      in fermentation solution.
AB  - An anion exchange method for lactic acid recovered from lactic acid-glucose
      solution in an ion-exchange membrane-based extractive fermentation system was
      examined. The exchange isotherms of anion exchange resins for lactic acid
      recovered were measured batchwise, and the exchange-desorption kinetics of lactic
      acid passing through the exchange column was investigated. The determined typical
      breakthrough and elution curves were measured and simulated by conventional mode.
      The mass transfer coefficients were identified by numberical method. The effects
      of the velocity of the fluid on the dynamics were studied. Aqueous NaOH solution
      was found to be the best solvent for elution. An experiment on anioun exchange
      from clarified lactic acid fermentation broth was carried out to obtain knowledge
      of the performance of the ion exchange system from a borth. The ion-exchange mass
      transfer coefficient and efficiency from the fermentation broth is found to be
      lower when compared with aqueous solutions of pure lactic acid. The results show
      that the separation method with anion exchange resins may be used in the
      production of lactic acid by fermentation.(c) 1995 John Wiley & Sons, Inc.

PMID- 18623362
TI  - Transport of lactate and acetate through the energized cytoplasmic membrane of
      Escherichia coli.
AB  - Escherichia coli produces lactate and acetate in significant amounts during both
      aerobic and anaerobic glycolysis. A model describing the mechanism of protein
      mediated lactate transport has previously bee proposed. A simple theoretical
      analysis here indicates that the proposed model would be drain cellular energy
      resources by catalytically dissipating the proton-motive force. An experimental
      analysis of lactate and acetate transport employ nuclear magnetic resonance (NMR)
      spectroscopy to measure the relative concentration of these end products on the
      two sides of the cytoplasmic membrane of anaerobically glycolyzing cells.
      Comparison of measured concentration rations to those expected at equilibrium for
      various transport modes indicates that acetate is a classical uncoupling agent,
      permeating the membrane oat comparable rates in the dissociated and undissociated
      forms. The lactate concentration ratio changes market markedly after an initial
      period of sustained glycolysis. This change is most readily explained as
      resulting from a lactate transport system that responds to an indicator of
      glycolytic activity. The data further indicates that lactate permeates the
      membrane in both dissociated and undissociated forms. Both acids, then are
      capable of catalytically dissipating the proton-motives force. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623364
TI  - Fundamental denitrification kinetic studies with Pseudomonas denitrificans.
AB  - Fundamental kinetic studies on the reduction of nitrate, nitrite, and their
      mixtures were performed with a strain of Pseudomonas denitrificans (ATCC 13867).
      Methanol served as the carbon source and was supplied in excess (2:1 mole ratio
      relative to nitrate and/or nitrite). Nitrate and nitrite served as terminal
      electron acceptors as well as sources of nitrogen for biomass synthesis. The
      results were explained under the assumption that respiration is a growth
      associated process. It was found that the sequence of complete reduction of
      nitrate to nitrogen gas is via nitrite and nitrous oxide.It was found that the
      specific growth rate of the biomass on either nitrate or nitrite follows Andrews
      inhibitory kinetics and nitrite is more inhibitory than nitrate. It was also
      found that the culture has severe maintenance requirements which can be described
      by Herbert's model, i.e., by self-oxidation of portions of the biomass. The
      specific maintenance rates at 30 degrees C and pH 7.1 were found to be equal to
      about 28% of the maximum specific growth rate on nitrate and 23% of the maximum
      specific growth rate on nitrite. Nitrate and nitrite were found to be involved in
      a cross-inhibitory noncompetitive kinetic interaction. The extent of this
      interaction is negligible when the presence of nitrite is low but is considerable
      when nitrite is present at levels above 15 mg/L.Studies on the effect of
      temperature have shown that the culture cannot grow at temperatures above 40
      degrees C. The optimal temperature for nitrate or nitrite reduction was found to
      be about 38 degrees C. Using an Arrhenius expression to describe the effect of
      temperature on the specific growth rates, it was found that the activation energy
      for the use of nitrate by the culture is 8.6 kcal/mol and 7.21 kcal/mol for
      nitrite. Arrhenius-type expressions were also used in describing the effect of
      temperature on each of the parameters appearing in the specific growth rate
      expressions. Studies on the effect of pH at 30 degrees C have shown that the
      culture reduces nitrate optimally at a pH between 7.4 and 7.6, and nitrite at a
      pH between 7.2 and 7.3. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623363
TI  - Polymerized liposome as ligand carrier for affinity precipitation of proteins.
AB  - A polymerized liposome (PLS) was prepared using a synthesized phospholipid with a
      diacetylene moiety in the hydrophobic chain and an amino group in the hydrophilic
      head. The PLS was used as a novel ligand carrier for affinity precipitation of
      proteins because it showed a reversibly precipitable property on salt addition
      and removal. Soybean trypsin inhibitor (STI) was easily immobilized on the PLS by
      a one-step carbodiimide reaction. The PLS showed no nonspecific adsoprtion of
      proteins. It had a large ligand coupling capacity, and then a large adsorption
      capacity for trypsin after STI immobilization. The PLS with immpbilized STI was
      recycled three times for the purification of trypsin from a crude pancreatic
      extract. Although the degree of purification was compromised by the impurity of
      the STI employed, in each run the purification factor reached about 6 and more
      than 80% of trypsin activity was recovered. The results indicated that the PLS
      was a potential ligand carrier for affinity precipitation of proteins. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623365
TI  - Growth kinetics of glucose-limited petunia hybrida cells in chemostat cultures:
      Determination of experimental values for growth and maintenance parameters.
AB  - With glucose-limited continuous cultures of Petunia hybrida six steady states
      were obtained at specific growth rates varying from 0.0035 to 0.012 h(-1)
      (corresponding with culture residence times varying from 285 to 85 h). The
      macromolecular and the elemental biomass composition which were determined in
      four steady states showed no major differences over the range of growth rates
      examined. During all six steady states specific subtrate and oxygen consumption
      as well as biomass and extracellular product formation rates were monitored.
      Moreover the specific activities of the mitochondrial cytochrome and alternative
      pathway were determined and used to estimate specific adenosine triphosphate
      (ATP) production rates. Data thus obtained were used in the determination of
      maintenance and true growth yield parameters. For the maintenance on glucose and
      ATP values of 0.0070 C-mol/C-mol/h and 0.034 mol/C-mol/h were obtained,
      respectively. True yields of biomass on glucose and ATP were 0.50 C-mol/C-mol and
      0.28 C-mol/mol, respectively. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623366
TI  - Two-stage batch process for the production of ajmalicine by Catharanthus roseus:
      The link between growth and production stage.
AB  - The link between the growth stage and the production stage in a two-stage batch
      process was investigated using (filtered) inocula from different periods of the
      stationary phase of the growth cycle. In the production stage, ajmalicine
      production by Catharanthus roseus in a 3-L stirred tank reactor was induced with
      a high glucose concentration (80 g/L). Ajmalicine production in cultures started
      with cells from the late stationary phase was five times higher than in cultures
      started with cells from the early stationary phase. After transfer to the
      production stage, cells from the early stationary phase showed a transient
      increase in respiration and enzyme induction, followed by culture browning. In
      contrast, cells in the late stationary phase showed a typical induction pattern:
      constant respiration, and permanent enzyme induction. A striking similarity
      between the geraniol-10-hydroxylase (G10H) activity and the ajmalicine
      accumulation profile could be observed in all cultures, suggesting that G 10H
      regulated ajmalicine production in this investigation. The intracellular nitrate
      concentration was significantly higher in the inoculum showing a high ajmalicine
      production than in the inoculum with a low production. Consequently, nitrate may
      act as a marker for the start of the production stage: as soon as the nitrate is
      depleted in the growth medium secondary metabolism can be induced. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623367
TI  - A comparison of lipase-catalyzed ester hydrolysis in reverse micelles, organic
      solvents, and biphasic systems.
AB  - The performance of lipases from Candida rugosa and wheat germ have been
      investigated in three reaction media using three acetate hydrolyses as model
      reactions (ethyl acetate, allyl acetate, and prenyl acetate). The effect of
      substrate properties and water content were studied for each system (organic
      solvent, biphasic system, and reverse micelles). Not unexpectedly, the effect of
      water content is distinct for each system, and the optimal water content for
      enzyme activity is not always the same as that for productivity. A theoretical
      model has been used to simulate and predict enzyme performance in reverse
      micelles, and a proposed partitioning model for biphasic systems agrees well with
      experimental results. While the highest activities observed were in the micellar
      system, productivity in microemulsions is limited by low enzyme concentrations.
      Biphasic systems, however, support relatively good activity and productivity. The
      addition of water to dry organic solvents, combined with the dispersion of
      lyophilized enzyme powders in the solvent, resulted in significant enzyme
      aggregation, which not surprisingly limits the applicability of the "anhydrous"
      enzyme suspension approach. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623368
TI  - Do organic solvents affect the catalytic properties of lipase? Intrinsic kinetic
      parameters of lipases in ester hydrolysis and formation in various organic
      solvents.
AB  - When it is assumed that organic solvents do not interfere with the binding
      process nor with the catalytic mechanism, the contribution of substrate-solvent
      interactions to enzyme kinetics can be accounted for by just replacing substrate
      concentrations in the equations by thermodynamic activities. It appears from the
      transformation that only the affinity parameters (K(m), K(sp)) are affected by
      this. Thus, in theory, the values of these corrected, intrinsic parameters (K(m)
      (int), k(sp) (int)) and the maximal rate (V(1)) should be equal for all media.
      This was tested for hydrolysis, transesterification, and esterification reactions
      catalyzed by pig pancreas lipase and Pseudomonas cepacia lipase in various
      organic solvents. Correction was carried out via experimentally determined
      activity coefficients for the substrates in these solvents or, if not feasible,
      from values in data bases. However, although the kinetic performances of each
      enzyme in the solvents became much more similar after correction, differences
      still remained. Analysis of the enzyme suspensions revealed massive particles,
      which explains the low activity of enzymes in organic solvents. However, no
      correlation was found between estimates of the amount of catalytically available
      enzyme (present at the surface of suspended particles or immobilized on beads)
      and the maximal rates observed. Moreover, the solvents had similar effects on the
      intrinsic parameters of suspended and immobilized enzyme. The possible causes for
      the effects of the solvents on the catalytic performance of the enzymes,
      remaining after correction for solvent-substrate interactions and the amount of
      participating enzyme, are discussed with respect to the premises on which the
      correction method is based. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623369
TI  - Membrane-attached biofilms for VOC wastewater treatment I: Novel in situ biofilm
      thickness measurement technique.
AB  - This article reports a novel nondisruptive technique for measuring the
      thicknesses of membrane-attached biofilms in situ, using a single tube extractive
      membrane bioreactor (STEMB). The biodegradation of a toxic volatile organic
      compound (VOC) (1,2-dichloroethane [DCE]) by Xanthobacter autotrophicus GJ10 has
      been used as a model system to develop the technique. The results give
      information on the biomass-silicone rubber attachment phenomena, and on the
      development over time of biofilms growing on the silicone membrane, without
      disrupting operation. Experimental results are presented showing the evolution
      over time of biofilm thickness, and also the density of biofilms for four
      experimental runs. The hydrodynamic conditions on the biomedium side of the
      membrane were found to influence the initial attachment phenomena and subsequent
      biofilm growth. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623370
TI  - Membrane-attached biofilms for VOC wastewater treatment. II: Effect of biofilm
      thickness on performance.
AB  - This article reports a study of the performance of membrane-attached biofilms
      grown in a single tube extractive membrane bioreactor (STEMS) used for the
      treatment of a synthetic wastewater containing a toxic VOC (1,2-dichloroethane
      [DCE]). Mass balances show that complete mineralization of DCE was achieved, and
      that the biofilms were effective in reducing air stripping to negligible levels.
      Experimental results are presented showing the evolution over time of biofilm
      thickness and its influence on the flux of DCE across the membrane. It has been
      found that a trade-off exists between the positive influence of biofilms in
      reducing air-stripping of DCE, and the negative influence of biofilms in reducing
      DCE flux across the membrane. These considerations lead to an optimal biofilm
      thickness in the region of 200 to 400 mum being recommended for this system. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623371
TI  - The effect of ammonia on the O-linked glycosylation of granulocyte colony
      stimulating factor produced by chinese hamster ovary cells.
AB  - Ammonium ion concentrations ranging from 0 to 10 mM are shown to significantly
      reduce the sialylation of granuiocyte colony-stimulating factor (G-CSF) produced
      by recombinant Chinese hamster ovary cells. Specifically, the degree of
      completion of the final reaction in the O-linked glycosylation pathway, the
      addition of sialic acid in an alpha(2,6) linkage to N-acetylgalactosamine, is
      reduced by NH(4) (+) concentrations of as low as 2 mM. The effect of ammonia on
      sialylation is rapid, sustained, and does not affect the secretion rate of G-CSF.
      Additionally, the effect can be mimicked using the weak base chloroquine,
      suggesting that the effect is related to the weak base characteristics of
      ammonia. In support of this hypothesis, experiments using brefeldin A suggest
      that the addition of sialic acid in an alpha(2,6) linkage to N
      acetylgalactosamine occurs in the trans-Golgi compartment prior to the trans
      Golgi network, which would be expected under normal conditions to have a slightly
      acidic pH in the range from 6.5 to 6.75. Ammonium ion concentrations of 10 mM
      would be expected to reduce significantly the differences in pH between acidic
      intracellular compartments and the cytoplasm. The pH-activity profile for the CHO
      O-linked alpha(2,6) sialytransferase using monosialylated G-CSF as a substrate
      reveals a twofold decrease in enzymatic activity across the pH range from 6.75 to
      7.0.Mathematical modeling of this sialylation reaction supports the hypothesis
      that this twofold decrease in sialyltransferase activity resulting from an
      ammoniainduced increase in trans-Golgi pH could produce the observed decrease in
      G-CSF sialylation. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623372
TI  - In situ microscopy for on-line characterization of cell-populations in
      bioreactors, including cell-concentration measurements by depth from focus.
AB  - A new technique is presented which allows the use of a front-end sensor head for
      in situ and on-line characterization of cell concentration and cell size during
      fermentation. An epifluorescence microscope is mounted in a port of a bioreactor
      viewing directly into the agitated broth. Still images from cells are generated
      using pulsed illumination. They are directly visualized on a monitor and used for
      automatic image analysis. The cell concentration and morphological information
      are determined by counting and evaluating the cell images with respect to their
      depth from focus characteristic. An in situ microscope was successfully tested
      during yeast fermentations and yielded results which correlated well with results
      from a hemocytometer. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623373
TI  - Kinetics of phenolic polymerization catalyzed by peroxidase in organic media.
AB  - Phenolic polymerization was carried out by enzymatic catalysis in organic media,
      and its kinetics was studied by using high-pressure liquid chromatography (HPLC).
      Phenols and aromatic amines with electron-withdrawing groups could hardly be
      polymerized by HRP catalysis, but phenols and aromatic amines with electron
      donating groups could easily be polymerized. The reaction rate of either the para
      substituted substrate or meta-substituted substrate was higher than that of ortho
      substituted substrate. When ortho-position of hydroxy group of phenols was
      occupied by an electron-donating group and if another electron-donating group
      occupied para-position of hydroxy group, the reaction rate increased. Horseradish
      peroxidase and lactoperoxidase could easily catalyze the polymerization, but
      chloroperoxidase and laccase failed to yield polymers. Metallic ions such as
      Mn(2+), Fe(2+), or Fe(3+), and Cu(2+) could poison horseradish peroxidase to
      various extents, but ions such as Co(2+), Cd(2+), Zn(2+), and K(+) were not found
      to inhibit the reaction. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623374
TI  - Influence of water activity on the synthesis of triolein catalyzed by immobilized
      mucor miehei lipase.

PMID- 18623375
TI  - Improved survival with adjuvant external-beam radiation therapy in lymph node
      negative pancreatic cancer: a United States population-based assessment.

PMID- 18623376
TI  - Myeloid sarcoma is associated with superior event-free survival and overall
      survival compared with acute myeloid leukemia.
AB  - BACKGROUND: It is unknown whether patients with nonleukemic myeloid sarcoma (MS)
      and those with acute myeloid leukemia (AML) have similar responses to anti-AML
      treatment. In the current study, the authors addressed this question by matching
      MS patients with analogous AML patients and comparing their clinical outcomes.
      METHODS: Twenty-three consecutive patients with MS and 1720 consecutive patients
      with AML were identified who presented at The University of Texas M. D. Anderson
      Cancer Center from 1990 to 2004. All AML patients and 16 MS patients received
      cytarabine plus idarubicin or fludarabine as induction remission therapy. Treated
      MS patients and AML patients were matched according to cytogenetics, age, Zubrod
      performance status, and time of treatment. Event-free survival (EFS) and overall
      survival (OS) were compared using Kaplan-Meier analyses. RESULTS: Complete
      response rates were 69% in patients with MS and 57% in patients with AML (P =
      .45). The respective 2-year EFS and OS rates were 32% and 18% (P = .08) and 43%
      and 29% (P = .11). Matches were identified for 14 MS patients who were paired
      repeatedly with 91 AML patients to produce 94 matches (3 AML patients were
      matched twice). EFS was longer in 56 MS pair mates, shorter in 26 pair mates, and
      similar in 12 pair mates (P = .01; Fisher exact test). OS analyses yielded
      similar results. CONCLUSIONS: Anti-AML therapy was highly effective in patients
      with nonleukemic MS. The results from this study emphasize the need to treat
      patients who have nonleukemic MS with AML-type therapy.

PMID- 18623378
TI  - ERCC1 expression as a prognostic marker in N2(+) nonsmall-cell lung cancer
      patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy.
AB  - BACKGROUND: Excision repair cross-complementation Group 1 (ERCC1) overexpression
      is associated with resistance to cisplatin-based chemotherapy in patients with
      nonsmall-cell lung cancer (NSCLC). A preliminary study also suggested that ERCC1
      expression is associated with radioresistance in lung cancer cells. The aim of
      this study was to evaluate the clinical implications of ERCC1 expression in stage
      IIIA N2-positive NSCLC patients treated with platinum-based neoadjuvant
      concurrent chemoradiotherapy (CCRT) followed by surgery. METHODS: Sixty-eight
      patients with mediastinoscopy-proven N2-positive NSCLC were enrolled between
      August 1997 and September 2003. ERCC1 expression was assessed by
      immunohistochemistry from pretreatment mediastinoscopic biopsy specimens.
      RESULTS: ERCC1 expression was positive in 31 of 68 specimens (46%). Among 14
      patients who obtained pathologic complete response, 6 were positive for ERCC1
      expression and 8 were negative (P = .818). On univariate analysis, with median
      follow-up of 61.8 months (range, 34.3-108.8 months), progression-free survival
      was 15.9 months for ERCC1-positive and 29.5 months for ERCC1-negative patients (P
      = .062), and there was a statistically significant difference in overall survival
      between ERCC1-negative tumors and ERCC1-positive tumors (89.2 vs 26.0 months, P =
      .014). On multivariate analysis, ERCC1 negativity (P = .041) and achieving
      mediastinal nodal clearance (downstage to pathological N0 or N1) after
      neoadjuvant CCRT followed by surgery (P = .005) were significant independent
      prognostic factors for the prolongation of survival. CONCLUSIONS: These results
      suggest that N2-positive NSCLC patients with ERCC1 negative tumors show a
      survival benefit from neoadjuvant CCRT with a platinum-containing regimen.

PMID- 18623377
TI  - High-dose therapy and autologous stem cell transplantation for chemoresistant
      Hodgkin lymphoma: the Seattle experience.
AB  - BACKGROUND: High-dose therapy (HDT) with autologous stem cell transplantation
      (ASCT) is the standard treatment for patients with chemosensitive
      relapsed/refractory Hodgkin lymphoma (HL), but this therapy is commonly denied to
      patients with resistant disease. We explored the utility of HDT and ASCT for
      chemoresistant HL because there are few established therapies for these patients.
      METHODS: Sixty-four chemoresistant HL patients underwent HDT followed by ASCT at
      our center. Baseline characteristics included median age = 35 years (range, 14-59
      years), stage III/IV = 49 (77%), nodular sclerosis histology = 51 (80%), and
      prior radiation = 32 (50%). Twenty-six patients (41%) received total body
      irradiation (TBI)-based regimens, and 38 (59%) underwent non-TBI conditioning.
      RESULTS: The estimated 5-year overall survival (OS) and progression-free survival
      (PFS) were 31% and 17%, respectively (median follow-up = 4.2 years). Multivariate
      analysis only identified year of transplant as independently associated with
      improved OS (P = .008) and PFS (P = .04), with patients receiving transplants in
      later years having better outcome. The probabilities of 3-year PFS for patients
      receiving transplants during 1986 to 1989, 1990 to July 1993, August 1993 to
      1999, and 2000 to 2005 were 9%, 21%, 33%, and 31%, respectively. CONCLUSIONS:
      These data suggest that HDT and ASCT may result in prolonged remissions and
      survival for a subset of chemoresistant HL patients, with improved outcomes in
      patients receiving transplants more recently.

PMID- 18623380
TI  - Application of cryobiopsy to morphological and immunohistochemical analyses of
      xenografted human lung cancer tissues and functional blood vessels.
AB  - BACKGROUND: Assessment of tissue specimens obtained with common immersion
      fixation followed by dehydration (IMDH) is affected by artifacts, which hinder
      precise evaluation of the histology and microenvironment of tumor tissues. The
      technical characteristics of cryobiopsy and in vivo cryotechnique (IVCT) where
      target organs are directly cryofixed in vivo are still unknown in practical
      examinations of tumor histopathology and microenvironment. METHODS: Three lines
      of human lung cancer cells were subcutaneously injected to the dorsal flank of
      nude mice, and paraffin sections and cryosections of produced tumors were
      prepared with cryobiopsy, IVCT, the quick-freezing of the fresh resected tumor
      tissues, or IMDH. Histological comparison among different methods was conducted,
      and immunolocalization of immunoglobulin M (IgM), intravenously injected bovine
      serum albumin (BSA), and vascular endothelial growth factor (VEGF) were examined.
      RESULTS: With both the cryobiopsy and IVCT, cellular morphology and open blood
      vessels with flowing erythrocytes could be observed without artificial shrinkage,
      and the volume of blood vessels was not affected by a vascular collapse, which
      was observed after tissue-resection. In addition, with cryobiopsy and IVCT, IgM
      was well preserved in functional vessels with blood flow, which could be observed
      with injected BSA, and the volume of IgM-immunopositive blood vessels was
      significantly associated with the expression of VEGF. CONCLUSIONS: Cryobiopsy
      could be useful for histological examination of human tumors without
      morphological artifacts associated with IMDH. Furthermore, it allows direct
      examination of functional blood vessels and related signaling molecules, thereby
      providing a better evaluation of the human tumor microenvironment for clinical
      application.

PMID- 18623382
TI  - Optimizing docetaxel chemotherapy in patients with cancer of the gastric and
      gastroesophageal junction: evolution of the docetaxel, cisplatin, and 5
      fluorouracil regimen.
AB  - Advanced gastroesophageal cancer patients are often treated with systemic
      combination chemotherapy. The V-325 study demonstrated that adding docetaxel (D)
      to a frequently used regimen of cisplatin and 5-fluorouracil (CF) provided
      benefits with regard to overall survival, response rate, time-to-disease
      progression, clinical benefit, and health-related quality of life. Although the
      DCF regimen provides these advantages, it is accompanied by an increase in
      toxicity compared with the doublet regimen. The toxicity profile of DCF is
      acceptable only with appropriately selected patients and comprehensive toxicity
      management strategies. The objective of the current review was to identify trials
      that investigated modifications to the original DCF regimen to improve its
      toxicity profile and summarize response rate and toxicities. An attempt was also
      made to summarize ongoing modifications of the DCF regimen. MEDLINE, major
      meeting proceedings, and the government clinical trials website were searched
      until 2007. The modified DCF regimens appear to improve the toxicity profile when
      compared with the original DCF regimen. The docetaxel-based triplet combinations
      appear to have a higher response rate than the doublet combinations. Many
      institutions and cooperative groups continue to study docetaxel-based
      modifications of the DCF regimen to treat patients with gastroesophageal
      carcinoma. However, although modified DCF reduces the frequency of severe
      toxicities previously reported with DCF, considerably more advances are needed to
      improve the safety, survival, and convenience of patients with advanced
      gastroesophageal cancer.

PMID- 18623384
TI  - Thermal isoelectric precipitation of alpha-lactalbumin from a whey protein
      concentrate: Influence of protein-calcium complexation.
AB  - The selective precipitation of alpha-lactalbumin (alpha-LA) at a pH around its
      isoelectric point (4.2) under heat treatment is the basis for a fractionation
      process of whey proteins. As precipitation is a phenomenon dependent on the
      protein hydrophobicity, and as the release of the tightly bound calcium occurring
      at pH around 4 modifies the alpha-LA hydrophobicity, the specific role of calcium
      on isoelectric precipitation is investigated. A study of the extent of alpha-LA
      precipitation in a whey protein concentrate under various operating conditions of
      pH, temperature, protein concentration, and calcium content is presented. We
      propose a mechanism for this phenomenon as a combination of a complexation
      equilibrium and of an irreversible precipitation, to account for the influence of
      temperature, alpha-LA concentration total ionic content, and calcium
      concentration, and also to estimate the complexation equilibrium constant. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623381
TI  - Influence of induction chemotherapy and class of cytotoxics on pathologic
      response and survival after preoperative chemoradiation in patients with
      carcinoma of the esophagus.
AB  - BACKGROUND: Patients with localized esophageal cancer (LEC) have diverse outcomes
      (post-therapy pathologic response, disease-free survival [DFS], and overall
      survival [OS]) after preoperative chemoradiation (P-CTRT), dictated also by
      inherent molecular heterogeneity. Whether the type of therapy influences the
      outcomes remains largely unanswered. It is hypothesized that induction
      chemotherapy (IC) or the type of cytotoxics used would not influence patient
      outcomes. METHODS: In this retrospective analysis, consecutive patients with LEC
      who had P-CTRT were analyzed. Data were collected regarding age, sex, baseline
      clinical stage, location, type of cytotoxics, post-therapy pathology, DFS, and
      OS. IC and the type of cytotoxics used were found to be correlated with DFS, OS,
      and post-therapy pathologic response. RESULTS: A total of 180 patients with LEC
      (119 had IC before P-CTRT, all had received 5-fluorouracil, 87 had received a
      taxane, and 57 had received a platinol) were analyzed. The median survival (MS)
      of all patients was 57.7 months and the 3-year and 5-year OS rates were 65.4% and
      46.5%, respectively. The type of therapy appeared to have no influence on the
      outcome: IC versus no IC (P = .58) or platinol versus taxane versus platinol plus
      taxane (P = .63). Similarly, the type of pathologic response was not found to be
      influenced by IC (P = .18) or the type of cytotoxics used (P = .42). The data
      were similar for DFS. CONCLUSIONS: IC or the type of cytotoxics used with
      radiation for patients with LEC does not appear to influence OS, DFS, or the type
      of pathologic response after therapy, suggesting that a plateau has been reached.
      It remains to be seen whether the use of biochemoradiotherapy can provide an
      advantage in outcome.

PMID- 18623385
TI  - Growth kinetics of vitis vinifera cell suspension cultures: I. Shake flask
      cultures.
AB  - Vitis vinifera cell suspension cultures carried out in shake flasks were closely
      examined for biomass growth and cell division in relation to carbohydrate, NH(4),
      NO(3)PO(4), and dissolved oxygen (DO)consumption. After inoculation, the oxygen
      uptake rate of the cultures measured on-tine was observed to increase
      continuously to a maximum value of 3.8 mmol O(2)L(-1)h(-1) at day 7 when cell
      division ceased and dissolved oxygen reached its lowest level of 17% air
      saturation. During this first phase of growth, the specific oxygen uptake rate
      remained constant at approximately 0.6 mmol 02 O(2) g(-1) dw h(-1)or
      approximately 2.2 mumol O(2), (10(6) cells)(-1) h(-1) whereas dry biomass
      concentration increased exponentially from 1.5 to 6.0 g dw L(-1). Thereafter, dry
      biomass concentration increased linearly to approximately 14 g dw L(-1) at day 14
      following nitrate and carbohydrate uptake. During this second phase of growth,
      the biomass wet-to-dry weight ratio was found to increase in an inverse
      relationship with the estimated osmotic pressure of the culture medium. This
      corresponded to inflection points in the dry and wet biomass concentration and
      packed cell volume curves. Furthermore, growth and nutrient uptake results
      suggest that extracellular ammonium or phosphate ion availability may limit cell
      division. These findings indicate that cell division and biomass production of
      plant cell cultures may not always be completely associated, which suggests
      important new avenues to improve their productivity. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623386
TI  - Influence of substrate oscillations on acetate formation and growth yield in
      Escherichia coli glucose limited fed-batch cultivations.
AB  - A Large bioreactor is an inhomogenous system with concentration gradients which
      depend on the fluid dynamics and the mass transfer of the reactor, the feeding
      strategy, the saturation constant, and the cell density. The responses of
      Escherichia coli cells to short-term oscillations of the carbon/energy substrate
      in glucose limited fed-batch cultivations were studied in a two-compartment
      reactor system consisting of a stirred tank reactor (STR) and an aerated plug
      flow reactor (PFR) as a recycle loop. Short-term glucose excess or starvation in
      the PFR was simulated by feeding of glucose to the PFR or to the STR
      alternatively. The cellular response to repeated short-term glucose excess was a
      transient increase of glucose consumption and acetate formation. But, there was
      no accumulation of acetate in the culture, because it was consumed in the STR
      part where the glucose concentration was growth limiting. However, acetate
      accumulated during the cultivation if the oxygen supply in the PFR was
      insufficient, causing higher acetate formation. The biomass yield was then
      negatively influenced, which was also the case if the PFR was used to simulate a
      glucose starvation zone. The results suggest that short-term heterogeneities
      influence the cellular physiology and growth, and can be of major importance for
      the process performance. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623387
TI  - Production and properties of a bifunctional fusion protein that mediates
      attachment of vero cells to cellulosic matrices.
AB  - The sequence Arg-Gly-Asp (RGD) in extracellular matrix proteins such as
      fibronectin, collagen, and laminin mediates cell attachment by interacting with
      proteins of the integrin family of cell surface receptors. A gene fusion encoding
      the RGD-containing peptide, fused to the C-terminus of a cellulose-binding domain
      (CBD/RGD), was expressed in Escherichia coli. Cultures produced up to 50 mg of
      CBD/RGD per liter, most of which was extracellular. It was purified from the
      culture supernatant by affinity chromatography on cellulose. CBD/RGD promoted the
      attachment of green monkey Vero cells to polystyrene and cellulose acetate.
      Attachment was inhibited by small synthetic peptides containing the RGD sequence.
      CBD/RGD was as effective as collagen in promoting the attachment of Vero cells to
      Cellsnowtrade mark microcarriers. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623388
TI  - Protein recovery from cell debris using rotary and tangential crossflow
      microfiltration.
AB  - Protein recovery from a bacterial lysate was accomplished using microfiltration
      membranes in a flat crossflow filter and in a cylindrical rotary filter. Severe
      membrane fouling yielded relatively low long-term permeate flux values of 10(-4)
      10(-3) cm/s (where I cm/s = 3.6 x 10(4) L/m(2) - h). The permeate flux was found
      to be nearly independent of transmembrane pressure and to increase with
      increasing shear rate and decreasing solids concentration. The flux increased
      with shear to approximately the one-third power or greater for the flat filter
      and the one-half power or greater for the rotary filter; the stronger dependence
      for the rotary filter is thought to result from Taylor vortices enhancing the
      back transport of debris carried to the membrane surface by the permeate flow.
      The average protein transmission or sieving coefficient was measured at
      approximately 0.6, but considerable scatter in the transmission data was
      observed. The largest sieving coefficients were obtained for dilute suspensions
      at high shear rate. The rotary filter provided higher fluxes than did the flat
      filter for dilute suspensions, but not for concentrated suspensions. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623389
TI  - On-line state recognition in a yeast fed-batch culture using error vectors.
AB  - The physiological states with respect to cell growth and ethanol production in a
      yeast fed-batch culture expressed in linguistic form could be recognized on-line
      by fuzzy inferencing based on error vectors. The error vector was newly defined
      here in a macroscopic elemental balance equation. The physiological states for
      cell growth and ethanol production were characterized by error vectors using many
      experimental data from fed-batch cultures. Fuzzy membership functions were
      constructed from the frequency distributions of the error vectors and state
      recognition was performed by fuzzy inferencing. In particular, an unusual
      physiological state for a yeast cultivation, in which aerobic ethanol production
      was accompanied by very low cell growth, could be recognized accurately.
      According to the results of the state recognition, an energy parameter, the P/O
      ratio in the metabolic reaction model was adaptively estimated, and the cell
      growth was successfully evaluated with the estimated P/O. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623390
TI  - Effect of membrane morphology and operation on protein deposition in
      ultrafiltration membranes.
AB  - Membrane morphology is compared to protein depostion under passive adsorption and
      ultrafiltration conditions. Solute resistance of protein deposits for membranes
      of varying roughness, structure, and permeability can vary dramatically with
      operating conditions. Using Brunauer-Emmett-Teller adsorption isotherm (BET),
      study of the internal area and accessibility of several uttrafiltration membranes
      to protein deposition allows better understanding of the fouling mechanisms and
      interpretation of adsorbed protein quantities. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623391
TI  - Effect of insulin on a serum-free hybridoma culture.
AB  - Insulin is often included in serum-free media for animal cell cultivation.
      However, the necessity of insulin for a specific cell line is rather uncertain.
      In this article we report the effects of insulin on the cultivation of a
      hybridoma cell line in a serum-free medium. It was found that insulin affected
      neither the cell growth nor the antibody production. The specific growth rate and
      specific antibody production rate were very similar in the cultures with or
      without insulin. However, the presence of insulin affected the nutrient
      consumption rate and cell metabolism. Including insulin in the medium resulted in
      a higher specific glucose consumption rate, a shorter exponential growth stage,
      and a lower final antibody concentration. The elimination of insulin from the
      medium allowed antibody to accumulate to a concentration substantially higher
      than that in the insulin-containing cultuvre. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623392
TI  - Characterization of a pH-inducible promoter system for high-level expression of
      recombinant proteins in Escherichia coli.
AB  - A pH-inducible promoter system was characterized and its potential applicability
      in recombinant protein production was evaluated using a plasmid construct, pSM552
      545C(-), in which the promoter and activator coding sequences of the cad operon
      were inserted into the upstream region of a lacZ' reporter gene. Graded gene
      expression levels with respect to culture pH between 8.0 and 5.5 were observed
      and the induction range can be as high as 200-fold. The effects of several
      cultivation parameters, including pH, temperature, induction cell density, and
      inoculum size, were systematically examined. The practical application of this
      expression system to high level production of recombinant proteins was
      successfully demonstrated using a rich medium, superbroth. An extremely high
      recombinant protein productivity at a value of approximately 1.4 g/L with a
      specific expression level as high as 35% of total cellular protein can be
      obtained in a simple batch cultivation. The behavior of this expression system
      was further investigated using chemostat cultures. An uncommon relationship
      between the volumetric or specific recombinant protein activity and the dilution
      rate, with a maximal activity at a dilution rate of approximately 0.4 h(-1)was
      observed. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623393
TI  - Fluxes of carbon, phosphorylation, and redox intermediates during growth of
      saccharomyces cerevisiae on different carbon sources.
AB  - In the present work we develop a method for estimating anabolic fluxes when yeast
      are growing on various carbon substrates (glucose, glycerol, lactate, pyruvate,
      acetate, or ethanol) in minimal medium. Fluxes through the central amphibolic
      pathways were calculated from the product of the total required amount of a
      specified carbon intermediate times the growth rate. The required amount of each
      carbon intermediate was estimated from the experimentally determined
      macromolecular composition of cells grown in each carbon source and the monomer
      composition of macromolecules.Substrates sharing most metabolic pathways such as
      ethanol and acetate, despite changes in the macromolecular composition, namely
      carbohydrate content (34% +/- 1 and 21% +/- 3, respectively), did not show large
      variations in the overall fluxes through the main amphibolic pathways. For
      instance, in order to supply anabolic precursors to sustain growth rates in the
      range of 0.16/h to 0.205/h, similar large fluxes through Acetyl CoA synthase were
      required by acetate (4.2 mmol/hr g dw) or ethanol (5.2 mmol/h g dw).The V(max)
      activities of key enzymes of the main amphibolic pathways measured in
      permeabilized yeast cells allowed to confirm, qualitatively, the operation of
      those pathways for all substrates and were consistent on most substrates with the
      estimated fluxes required to sustain growth.When ATP produced from oxidation of
      the NADH synthesized along with the key intermediary metabolites was taken into
      account, higher Y(ATP) (max) values (36 with respect to 24 g dw/mol ATP) were
      obtained for glucose. The same result was obtained for glycerol, ethanol, and
      acetate. A yield index (YI) was defined as the ratio of the theoretically
      estimated substrate flux required to sustain a given growth rate over the
      experimentally measured flux of substrate consumption. Comparison of Yl between
      growth on various carbon sources led us to conclude that ethanol (Yl = 0.84),
      acetate (Yl = 0.77), and lactate (Yl = 0.77) displayed the most efficient use of
      substrate for biomass production. For the other substrates, the Yl decayed in the
      following order: pyruvate > glycerol > glucose.An improvement of the quantitative
      understanding of yeast metabolism, energetics, and physiology is provided by the
      present analysis. The methodology proposed can be applied to other eukaryotic
      organisms of known chemical composition. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623394
TI  - Production of a lipopeptide antibiotic, surfactin, by recombinant Bacillus
      subtilis in solid state fermentation.
AB  - Production of a lipopeptide antibiotic, surfactin, in solid state fermentation
      (SSF) on soybean curd residue, Okara, as a solid substrate was carried out using
      Bacillus subtilis MI113 with a recombinant plasmid pC112, which contains lpa-14,
      a gene related to surfactin production cloned at our laboratory from a wild-type
      surfactin producer, B. subtilis RB14. The optimal moisture content and
      temperature for the production of surfactin were 82% and 37 degrees C,
      respectively. The amount of surfactin produced by MI113 (pC112) was as high as
      2.0 g/kg wet weight, which was eight times as high as that of the original B.
      subtilis RB14 at the optimal temperature for surfactin production, 30 degrees C.
      Although the stability of the plasmid showed a similar pattern in both SSF and
      submerged fermentation (SMF), production of surfactin in SSF was 4-5 times more
      efficient than in SMF. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623395
TI  - Equilibria for the adsorption of antibiotics onto neutral polymeric sorbents:
      Experimental and modeling studies.
AB  - The objective of this work was to study the equilibria for adsorption of three
      antibiotics (penicillin V, tetracycline, and cephalosporin C) from water onto
      commercially available neutral polymeric sorbents. The pH was observed to be an
      important factor in adsorption as our results suggest that the neutral forms of
      penicillin V and cephalosporin C are preferentially adsorbed onto the neutral
      sorbents. Also, sorbent surface chemistry was observed to be important for
      adsorption, as the antibiotics adsorbed more favorably (both in terms of
      affinities and enthalpies) onto the aromatic sorbent as compared to the aliphatic
      ester sorbent. In addition to these thermodynamic measurements, molecular
      modeling studies and Monte Carlo simulations suggest that adsorption onto
      aromatic sorbents may involve specific interactions between the planar regions of
      the antibiotic molecules and the phenyl rings of the aromatic sorbent. The
      interaction energies predicted from Monte Carlo simulations were observed to
      provide qualitative agreement with experimentally determined adsorption
      affinities. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623396
TI  - Effect of yeast extract on growth kinetics during aerobic biodegradation of
      chlorobenzoic acids.
AB  - The Monod or Andrews kinetic parameters describing the growth of Pseudomonas sp.
      CPE2 strain on 2,5-dich!orobenzoic acid and 2-chlorobenzoic acid, and Al
      caligenes sp. CPE3 strain on 3,4-dichlorobenzoic acid, 4-chlorobenzoic acid, and
      3-chlorobenzoic acid were determined from batch and continuous growth experiments
      conducted in the presence or absence of yeast extract (50 mg/L). Strain CPE2
      displayed inhibitory growth kinetics in the absence of yeast extract and a
      noninhibitory kinetics in the presence of yeast extract. Similar results were
      obtained for CPE3. The presence of yeast extract also resulted in a significant
      increase in the affinity of the strains for the chlorobenzoic acids they
      degraded. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623397
TI  - Studies of transcriptional state heterogeneity in sporulating cultures of
      bacillus subtilis.
AB  - Using a flow cytometry-based technique for detecting p-galactosidase. lacZ
      fusions have been used to study the pattern of gene expression exhibited by
      stationary phase cultures of Bacillus subtilis that have initiated the
      developmental pathway of spore formation. We have found that within such cultures
      there exist two distinct cell types: one that has induced the developmental
      program of gene expression and one that has not. This heterogeneity among
      transcriptional states is shown to be established early during the stationary
      phase and plays a significant role in influencing later stationary phase events.
      Additionally, when this technique is used to study gene expression in mutants
      that display altered patterns of gene expression, we are able to conclude that
      the cellular apparatus responsible for sensing and transducing stationary phase
      developmental signals represents a bottleneck that controls the expression of
      certain early stationary phase genes. These findings provide a demonstration of
      the utility of single cell measurements of gene expression and indicate that
      unless culture heterogeneity is properly taken into account, standard
      measurements of gene expression may not provide information suitable for the
      analysis of events occurring at the cellular level. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623398
TI  - Stability of transfectomas producing chimeric antibody against the pre-S2 surface
      antigen of hepatitis B virus during a long-term culture.
AB  - To design the scheme of large-scale production of chimeric antibody for the
      postexposure prophylaxis of hepatitis B virus (HBV) infection, the stability of
      transfectomas (H69K-1 and 6-31) in regard to antibody production was examined
      during a long-term, repeated fed-batch culture without selection pressure using
      antibiotics. Although the H69K-1 transfectoma was more stable than the 6-31
      transfectoma, both displayed gradual decreases in specific antibody productivity
      (q(Ab)) for the first several weeks of cultivation. During this period, q(Ab) was
      de-creased by 40% to 50%. This loss of q(Ab) was due mainly to the appearance of
      a nonproducing population (NP) of transfectoma, which was monitored throughout
      the culture by flow cytometry and the limiting dilution method. However, an NP
      did not overtake the culture and was balanced with a producing population (P) of
      transfectoma, resulting in stable antibody production. The subclones of NP
      obtained at the end of long-term culture were further characterized by reverse
      transcription-polymerase chain reaction assay of the heavy and light chain mRNA.
      All the subclones of NP derived from H69K-1 transfectoma had only light chain
      mRNA. On the other hand, an NP in the 6-31 transfectoma culture was
      heterogeneous. Some subclones of NP derived from 6-31 transfectoma had only heavy
      chain mRNA and other subclones had only light chain mRNA. Taken together, the
      results obtained here suggest that selection pressure is necessary for a long
      term, continuous culture, because stable antibody production in a long-term
      culture was achieved only after a significant loss of antibody productivity.
      Accordingly, a batch culture appears to be more appropriate for large-scale
      chimeric antibody production without selection pressure. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623399
TI  - The influence of electrostatic interactions on partition in aqueous polyethylene
      glycol/dextran biphasic systems: Part II.
AB  - In aqueous polyethylene glycol/dextran two-phase systems, the hydrophobicity,
      free volume, surface tension, and interfacial tension of the phases in
      equilibrium were measured as a function of pH and ionic strength. These
      parameters were found to change with pH, but the pattern and magnitude cannot
      explain the unusual partition of charged macromolecules, observed previously. The
      electrostatic potential difference was determined by a new experimental approach
      based on the measurement of the pH difference between the phases at equilibrium.
      In polyethylene glycol/dextran systems containing sodium chloride as ionized
      species, the electrostatic potential is not constant in the pH range 2 to 11. The
      partition behavior of charged macromolecules and its dependence on pH can be
      explained by the combined action of charge and phase potential. This conclusion
      was tested with poly-L-glutamate, which partitioned as predicted and in a pattern
      opposite to positively charged macro- molecules. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623400
TI  - Photosynthetic performance of a helical tubular photobioreactor incorporating the
      cyanobacterium spirulina platensis.
AB  - The photosynthetic performance of a helical tubular photobioreactor ("Biocoil"),
      incorporating the filamentous cyanobacterium Spirulina platensis, was
      investigated. The photobioreactor was constructed in a cylindrical shape (0.9 m
      high) with a 0.25-m(2)basal area and a photostage comprising 60 m of transparent
      PVC tubing of 1.6-cm inner diameter (volume = 12.1 L). The inner surface of the
      cylinder (area = 1.32 m(2)) was illuminated with cool white fluorescent lamps;
      the energy input of photosynthetically active radiation(PAR, 400 to 700 nm) into
      the photobioreactor was 2920 kJ per day. An air-lift system ncorporating 4%CO(2)
      was used to circulate the growth medium in the tubing. The maximum productivity
      achieved in batch culture was 7.18 g dry biomass per day [0.51 g . d biomass/L .
      day, or 5.44 g . d biomass/m(2)(inner surface of cylindrical shape)/day] which
      corresponded to a photosynthetic (PAR) efficiency of 5.45%. The CO(2) was
      efficiently removed from the gaseous stream; monitoring the CO(2) the outlet and
      inlet gas streams showed a 70% removal of CO(2) from the inlet gas over an 8-h
      period with almost maximum growth rate. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623401
TI  - Relationship between loss of heavy chains and the appearance of nonproducing
      hybridomas.
AB  - One drawback to the in vitro production of monoclonal antibodies is the loss of
      productivity exhibited by hybridomas over time, which has been shown to
      correspond to the appearance of a nonproducing subpopulation. In this study, we
      monitored the presence of antibody components, both intra- and extracellular,
      between producing and nonproducing hybridomas. A nonproducing cell population
      appeared which lacked heavy chain, while all cultures continued to produce light
      chain, indicating that the loss in antibody production resulted from the absence
      of heavy chain and occurred before protein assembly or secretion. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623403
TI  - A structured metabolic model for anaerobic and aerobic stoichiometry and kinetics
      of the biological phosphorus removal process.
AB  - A structured metabolic model is developed that describes the stoichiometry and
      kinetics of the biological P removal process. In this approach all relevant
      metabolic reactions underlying the metabolism, considering also components like
      adenosine triphosphate (ATP) and nic-otinamide-adenine dinucleotide (NADH(2)) are
      describedbased on biochemical pathways. As a consequence of the relations between
      the stoichiometry of the metabolic reactions and the reaction rates of
      components, the required number of kinetic relations to describe the process is
      reduced. The model describes the dynamics of the storage compounds which are
      considered separately from the active biomass. The model was validated in
      experiments at a constant sludge retention time of 8 days, over the anaerobic and
      aerobic phases in which the external oncentrations as well as the internal
      fractions of the relevant components involved in the P-removal process were
      monitored. These measurements include dissolved acetate, phosphate, and ammonium;
      oxygen consumption; poly-beta-hydroxybutyrate (PHB); glycogen; and active
      biomass. The model satisfactorily describes the dynamic behavior of all
      components during the anaerobicand aerobic phases.(c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623404
TI  - Affinity purification of proteins using ligands derived from peptide libraries.
AB  - Peptide libraries can be used to identify ligands that bind specifically to a
      desired protein. These peptides may have significant advantages as specific
      ligands for affinity chromatography separations. This article describes the use
      of one of such peptide, Try-Asn-Phe-Glu-Val-Leu, as a ligand for the purification
      of S-protein using affinity chromatography. General strategies for peptide
      immobilization are discussed and the conditions for peptide immobilization to
      Emphazetrade mark gel are optimized. The effects of peptide orientation and
      peptide densities on protein binding are studied. Results indicate that the
      peptide affinity is not affected by the orientation of the peptide during
      immobilization, but association constants can be reduced by one order of
      magnitude when compared with the values in solution.With increased peptide
      density, the protein binding capacity of the gel increases, but both the
      percentage of peptide utilization and apparent binding constant between
      immobilized peptide and S-protein decrease. S-protein is separated from a mixture
      with BSA via affinity chromatography using specific elution with the peptide in
      solution.Finally, direct purification of S-protein from an enzymatic digestion
      mixture of ribonuclease A is demonstrated.(c) 1995 John Wiley & Sons, Inc.

PMID- 18623405
TI  - High-rate continuous biodegradation of concentrated chlorinated aliphatics by a
      durable enrichment of methanogenic origin under carrier-dependent conditions.
AB  - The simultaneous biodegradation of toxic compounds in mixtures is a major current
      concern. To bioremediate a toxic mixture, we designed a strategy combining an ad
      sorbent carrier with an ecological and nutritional system which allowed work
      close to heavily polluted conditions in nature. Starting from a methanogenic
      community, we developed a microbial consortium acclimated to a mixture of about
      30 chlorinated aliphatics in a fixed-film stationary-bed bioreactor. Prior to the
      establishment of a durable period of dechlorination, an interval of progressive
      dechlorination of the toxic mixture was observed during which the excess of the
      toxic compounds was stored on the carrier. The latter, consisting of activated
      carbon in a polyurethane foam, allowed us to work at concentrations far above the
      solubility of the toxic compounds (apparent concentrations of about 10 g/L). The
      complete disappearance of hexachloroethane as well as its lower homologues, penta
      , tetra-, and trichloroethane, present in the toxic mixture, was observed.
      Additionally, octachlorocyclopentene, carbon tetrachloride, trichloro-ethylene,
      tetrachloroethylene, and hexachloro-1,3-butadiene also completely disappeared.
      For the four latter compounds, from mass balances in the bioreactor, degradation
      rates around 10 mumol/L per day were determined with total dechlorination. The
      enrichment culture thus developed exhibited high degradation performances similar
      to those reported in the literature for pure or enriched anaerobic microbial
      cultures in contact with a single toxic compound. The results demonstrate the
      possibility of concurrent high-rate degradation of several highly chlorinated
      toxic compounds, under conditions approximating field situations.(c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623406
TI  - In-situ removal of ammonium and lactate through electrical means for hybridoma
      cultures.
AB  - Ammonium and lactate are two known toxic products detrimental to mammalian cell
      growth and productivity. An electrokinetic technique, utilizing an
      electrophoretic mechanism, was developed to remove these cellular wastes in-situ
      from suspension hybridoma (ATCC CRL-1606) cultures to enhance cell growth and
      productivity. This technique applies continuously a dc electric field to
      selectively remove the electrically charged wastes. The experiments were shown to
      be successful in the removal of externally added 10 rnM ammonium and 45 mM
      lactate while maintaining the chemostatic condition of culture medium in a cell
      free condition under an electric current density of 50 A/m(2). Toxic levels of
      ammonium were added, ranging from 7.5 to 12.5 mM, at the start of the hybridoma
      culture, and the applied dc electric fields were able to completely remove these
      added materials. This in turn released the inhibition and restored the cell
      growth. Finally, this electrokinetic technique was applied to the batch and
      glutamine fed-batch hybridoma cultures. At an applied electric current density of
      50 A/m(2), this was able to completely remove cell-produced ammonium and
      increased the cell growth and antibody titer by 30% to 50%, respectively,
      compared to the control experiment in the absence of the electric field. Lastly,
      the applied electric current density of 50 A/m(2) did not affect cellular
      functionalities such as glucose and glutamine consumption and antibody
      productivity.(c) 1995 John Wiley & Sons, Inc.

PMID- 18623407
TI  - Nutrient enrichment and in-situ waste removal through electrical means for
      hybridoma cultures.
AB  - In-situ dc electric fields were applied to remove ammonium and lactate from
      suspension hybridoma cultures (ATCC-CRL-1606) which used enriched media. Nutrient
      concentration was increased fourfold above the normal concentration of DMEM to
      study enhanced protein product formation in a dc electric field. In the presence
      of the electric field, hybridoma growth and antibody production were increased
      1.5-fold (from 3.7 x 10(6) to 9.1 x 10(6) viable cells/mL) and twofold (from 170
      to 505 mg IgG/L), respectively, compared with the control. The effective removal
      of ammonium and lactate and increased concentrations of the various nutrients
      accounted for this enhancement. The enriched media caused the overflow metabolism
      of glucose, glutamine, and various essential amino acids. The overconsumption of
      glucose also produced substantial amounts of lactate, which in turn greatly
      increased the medium osmolarity. The increase in medium osmolarity is believed to
      be one of the causes of cell death in these culture systems.(c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623408
TI  - Biological sulphide oxidation in a fed-batch reactor.
AB  - This study shows that, in a sulphide-oxidizing bioreactor with a mixed culture of
      Thiobacilli, the formation of sulphur and sulphate as end-products from the
      oxidation of sulphide can be controiledinstantaneously and reversibiy by the
      amount of oxygen supplied. It was found that at sulphide loading rates of up to
      2.33 mmol7/L . h, both products can be formed already at oxygen concentrations
      below 0.1 mg/L. Because the microorganisms tend to form sulphate rather than
      forming sulphur, the oxygen concentration is not appropriate to optimize the
      sulphur production. Within less than 2 h, the system can be switched reversibly
      from sulphur to sulphate formation by adjusting the oxygen flow. This is below
      the minimum doubling time (2.85 h) of, e.g., Thiobacillus neapolitanus and
      Thiobacillus 0,(18) which indicates that one metabolic type of organism can
      probably perform both reactions. Under highly oxygen-limited circumstances, that
      is, at an oxygen/sulphide consumption ratio below 0.7 mol . h(-1) mol . h(-1)
      thiosulphate is abundantly formed. Because the chemical sulphide oxidation
      results mainly in the formation of thiosulphate, it is concluded that, under
      these circumstances, the biological oxidation capacity of the system is lower
      than the chemical oxidation capacity. The oxidation rate of the chemical sulphide
      oxidation can be described by a first-order process (k =-0.87 h(-1)).(c) 1995
      John Wiley & Sons, Inc.

PMID- 18623409
TI  - Mathematical modeling and analysis of glucose and glutamine utilization and
      regulation in cultures of continuous mammalian cells.
AB  - A number of factors have been shown to affect the metabolism of glucose and
      glutamine in mammalian cells and their mechanisms have been partially elucidated.
      Despite these efforts, a quantitative knowledge of the significance of these
      factors, the regulation of glucose and glutamine utilization, and particularly
      the interactions of these two nutrients is still lacking. Controversies exist in
      the literature. To clarify some of these controversies, mathematical models are
      proposed in this work which enable to separate and identify the effects of
      individual factors. Experimental data from five cell lines obtained in batch, fed
      batch, and continuous cultures, both under steady-state and transient conditions,
      were used to verify the model formulations. The resulting kinetic models
      successfully describe all these cultures. According to the models, the specific
      consumption rate of glucose (Q(Glc)) of continuous animal cells under normal
      culture conditions can be expressed as a sum of three parts: a part owing to cell
      growth; a part owing to glucose excess; and a part owing to glutamine regulation.
      The specific consumption rate of glutamine (q(Glc)7) can be expressed as a sum of
      only two parts: a part owing to cell growth; and a part owing to glutamine
      excess. Using the kinetic models the interaction and regulation of glucose and
      glutamine utilizations are quantitatively analyzed. The results indicate that,
      whereas q(Glc) is affected by glutamine, q(Gln) appears to be not or less
      significantly affected by glucose. It is also shown that the relative
      utilizations of glucose and glutamine by anabolism and catabolism are mainly
      affected by the residual concentrations of the respective compounds and are less
      sensitive to growth rate and the nature of growth limitation.(c) 1995 John Wiley
      & Sons, Inc.

PMID- 18623410
TI  - Improvement of Escherichia coli microaerobic oxygen metabolism by Vitreoscilla
      hemoglobin: New insights from NAD(P)H fluorescence and culture redox potential.
AB  - On-line NAD(P)H fluorescence and culture redox potential (CRP) measurements were
      utilized to investigate the role of Vitreoscilla hemoglobin (VHb) in perturbing
      oxygen metabolism of microaerobic Escherichia coli Batch cultures of a VHb
      synthesizing E. coli strain and the iso-genic control under fully aerated
      conditions were subject to several high/low oxygen transitions, and the NAD(P)H
      fluorescence and CRP were monitored during these passages. The presence of VHb
      decreased the rate of net NAD(P)H generation by 2.4-fold under diminishing oxygen
      tension. In the absence of aeration, the strain producing VHb maintained a steady
      NAD(P)H level 1.8-fold less than that of the control, indicating that the
      presence of VHb keeps E. coli in a more oxidized state under oxygen-limited
      conditions. Estimated from CRP, the oxygen uptake rates near anoxia were 25%
      higher for cells with VHb than those without. These results suggest that VHb
      expressing cells have a higher microaerobic electron transport chain turnover
      rate. To examine how NAD(P)H utilization of VHb-expressing cells responds to
      rapidly changing oxygen tension, which is common in large-scale fermentations, we
      pulsed air intermittently into a cell suspension and recorded the fluorescence
      response to the imposed dissolved oxygen (DO) fluctuation. Relative to the
      control, cells containing VHb had a sluggish fluorescence response to sudden
      changes of oxygen tension, suggesting that VHb buffers intracellular redox
      perturbations caused by extracellular DO fluctuations.(c) John Wiley & Sons, Inc.

PMID- 18623411
TI  - Optimization of step gradient separations: Consideration of nonlinear adsorption.
AB  - Nonlinear adsorption plays an important role in determining the chromatographic
      behavior of proteins in preparative ion-exchange chromatography. In this article,
      the steric mass action (SMA) isotherm is used in conjunction with a mass
      transport model to describe nonlinear cation-exchange chromatography. Excellent
      agreement is observed between simulated and experimental step gradient
      separations of the proteins alpha-chymotryp-sinogen A, cytochrome C, and
      lysozyme. A systematic method of selecting the optimum step gradient program for
      a given separation problem is presented and employed to study optimization of
      step gradient chromatography under conditions of high mass loading. This article
      includes consideration of the effects of the adsorption properties of the feed
      stream, the feed stream concentration, protein solubility, and otherconstraints
      on the optimum separation conditions.(c) John Wiley & Sons, Inc.

PMID- 18623412
TI  - Continuous monitoring of nitrogenase activity in Azotobacter vinelandii
      fermentation using off-gas mass spectrometry.
AB  - This study evaluated the feasibility of monitoring nitro-genase activity in situ
      through measurement of N(2) uptake rate (NUR) using off-gas mass spectrometry.
      Four 50-L cultures of Azotobacter vinelandii were grown aer-obically in nitrogen
      free medium to cell densities of 1.0-1.3gL(-1) magnetic-sector mass spectrometer
      was used to monitor NUR along with other gas exchange rates. The small specific
      uptake rate (1.2 mmol g(-1) h(-1)) and low cell density were found to lead to a
      NUR below the measurement accuracy limits under normal conditions. An operating
      strategy and feed gas mixture (40% O(2), 45% N(2) 15% Ar) were designed to
      improve the signal-to-noise ratio while maintaining dissolved O(2) and N(2)
      levels in desired ranges. The fraction of N(2) removed from the air stream was
      increased approximately 5-fold from 0.2% to 1.0% and the measurement noise was
      reduced 25-fold from a baseline of +/-5to +/-0.2 mmol L(-1) h(-1). The NUR
      measurements were compared against in vivo and in vitro acetylene reduction
      assays as well as on-line cell growth rate measurements. While electron transfer
      requirements predict an NUR-to-acetylene reduction rate ratio of 0.33, measured
      ratios for the in vivo and in vitro assays were 0.8 and 0.44, respectively. This
      suggests that other rate-limiting steps were present in the case of the in vivo
      assay. In accordance with reports in the literature, no concomitant hydrogen
      evolution was detected. This is the first reported continuous and direct
      measurement of NUR in fermentation and demonstrates a novel approach for
      improving measurement accuracy through rational adjustment of operating
      conditions. The technique has potential to provide useful insight for development
      and control of microbial nitrogen fixation processes.(c) John Wiley & Sons, Inc.

PMID- 18623413
TI  - Protein-free human-human hybridoma cultures in an intercalated-spiral alternate
      dead-ended hollow fiber bioreactor.
AB  - Batch cell cultures of a human-human hybridoma line in a convective flow dominant
      intercalated-spiral altetnate-dead-ended hollow fiber are compared with those
      using conventional axial-flow hollow fiber bioreactors and a stirred-tank
      bioreactor. Relatively short-term fed-batch and perfusion cell cultures were also
      employed for the intercalated-spiral bioreactor. When operating conditions of a
      batch intercalated-spiral bioreactor were properly chosen, the cell growth and
      substrate consumption paralleled that of a batch stirred-tank culture. The
      results verified the premise of the intercalated-spiral hollow fiber bioreactor
      that nutrient transport limitations can be eliminated when the convective flux
      through the extracapillary space is sufficiently high.(c) John Wiley & Sons, Inc.

PMID- 18623414
TI  - Crossflow filtration of baker's yeast with periodical stopping of permeation flow
      and bubbling.
AB  - The periodical stopping of permeation flow was applied to increase the permeation
      flux in crossflow filtration of commercially available baker's yeast cell
      suspension. The permeation flux after 3 h filtration in the crossflow filtration
      increased to 8 x 10(-5) m(3) /m(2) s (290 L/m(2) h) from 2 x 10(-5) m(3)/m(2) s
      (72 L/m(2) h) by applying the periodical stopping of permeation. Introduction of
      air bubbles during the stopping period of permeation further increased the
      flux.(c) John Wiley & Sons, Inc.

PMID- 18623415
TI  - Fluorophore-labeled carbohydrate analysis of immunoglobulin fusion proteins:
      Correlation of oligosaccharide content with in vivo clearance profile.

PMID- 18623417
TI  - Analysis of cell-to-bubble attachment in sparged bioreactors in the presence of
      cell-protecting additives.
AB  - To investigate the mechanisms of cell protection provided by medium additives
      against animal cell injury in sparged bioreactors, we have analyzed the effect of
      various additives on the cell-to-bubble attachment process using CHO cells in
      suspension. Cell-to-bubble attachment was examined using three experimental
      techniques: (1) cell-bubble induction time analysis (cell-to-bubble attachment
      times); (2) forming thin liquid films and observing the movement and location of
      cells in the thin films; and (3) foam flotation experiments. The induction times
      we measured for the various additives are as follows: no additive (50 to 500 ms),
      polyvinyl pyrrolidone (PVP: 20 to 500 ms), polyethylene glycol (PEG: 200 to 1000
      ms), 3% serum (500 to 1000 ms), polyvinyl alcohol (PVA: 2 to 10 s), Pluronic F68
      (5 to 20 s), and Methocel (20 to 60 s). In the thin film formation experiments,
      cells in medium with either F68, PVA, or Methocel quickly flowed out of draining
      thin liquid films and entered the plateau border. When using media with no
      additive or with serum, the flow of cells out of the thin liquid film and film
      drainage were slower than for media containing Pluronic F68. PVA, or Methocel.
      With PVP and PEG, the thin film drainage was much slower and cells remained
      trapped in the film. For the foam flotation experiments, a separation factor
      (ratio of cell concentration in the foam catch to that in the bubble column) was
      determined for the various additives. In the order of increasing separation
      factors (i.e., increasing cell attachment to bubbles), the additives are as
      follows: Methocel, PVA, Pluronic F68, 3% serum, serum-free medium with no
      additives, PEG, and PVP. Based on the results of these three different cell-to
      bubble attachment experiments, we have classified the cell-protecting additives
      into three groups: (1) Pluronic F68, PVA, and Methocel (reduced cell-to-bubble
      attachment); (2) PEG and PVP (high or increased cell-to-bubble attachment); and
      (3) FBS (reduced cell attachment butslower drainage films compared with F68, PVA,
      and Methocel with some cell entrapment in those films). These phenomena are
      discussed in relation to the interfacial properties of the media reported in a
      companion Study (this issue). (c) 1995 John Wiley & Sons Inc.

PMID- 18623418
TI  - Interfacial properties of cell culture media with cell-protecting additives.
AB  - In an effort to identify key rheological properties that contribute to cell
      protection against shear damage, we have measured surface shear and dilatationai
      viscosities, dynamic surface tension, foaminess, and foam stability for media
      containing cell-protecting additives. In a companion article,(18) we found that
      cell-to-bubble attachment was decreased in media containing Methocel, Pluronic
      F68, or polyvinyl alcohol (PVA). In medium containing polyethylene glycol (PEG)
      or potyvinyl-pyrrolidone (PVP), attachment was increased. PEG, PVP, serum (FBS),
      and serum albumin (BSA) increased the surface viscosity of the air/medium surface
      (thus, producing a more rigid interface), whereas F68 and PVA lowered it greatly.
      Foaming experiments showed that Methocel, PEG, PVA, and F68 decreased the foam
      half-life while FBS, BSA, and PVP were foam stabilizers. Interestingly, the foam
      stability of CHO cell suspensions decreased significantly for cell concentrations
      higher than ca. 2 x 10(6) cells/mL. Nonviable CHO cells reduced foam stability
      further. Dynamic surface tension values of the media tested were found
      significantly differentfrom their static surface tension values. The interfacial
      properties measured and the results presented in the companion study suggest that
      the additives that lower dynamic surface tension the most (Methocel, F68, and
      PVA) correlate well with reduced cell-to-bubble attachment, and thus, cell
      protection. Reduced dynamic surface tension with these additives implies faster
      surfactant adsorption, mobile interfaces, lower surface viscosity, and foam
      destabilization. Because PEG and PVP resulted in increased cell-to-bubble
      attachment and had different interfacial properties, a different mechanism
      (compared with Methocel, PVP, and F68) is apparently responsible for their
      protective effect. Finally, cell protection offered by FBS and BSA is attributed
      to the foam stabilization properties provided by these additives. (c) 1995 John
      Wiley & Sons Inc.

PMID- 18623419
TI  - Towards the development of artificial endocrine tissues: (31)P NMR spectroscopic
      studies of immunoisolated, insulin-secreting AtT-20 cells.
AB  - Transformed, insulin-secreting endocrine cells have been proposed as an
      alternative to islets for the development of a bioartificiat pancreas. With
      appropriate immunoprotection, such cells may be implanted without the need for
      patient immunosuppression. Use of continuous cell lines alleviates the cell
      availability limitation, but poses questions regarding thestability and
      biochemical and secretory function of the preparation, especially in the
      longterm. We have developed a bioreactor/perfusion system, compatible with a
      horizontal-bore NMR instrument, that can maintain immunoprotected endocrine cells
      for prolonged periods of time. (31)P NMR spectroscopy was used to study the
      bioenergetics of recombinant, insulin-secreting mouse pituitary AtT-20 cells
      entrapped as spheroids in calcium alginate/poly-L-lysine/alginate beads. NMR
      provided data verifying the macroscopic homogeneity within the bioreactor and
      allowing the evaluation of changes in cellular bioenergetics for a period of 70
      days under different culture conditions. Levels of high-energy phosphates changed
      slightly during the first 40 days of the experiment, then decreased considerably
      as cell death occurred. Rates of glucose consumption and insulin-related peptide
      secretion also remained constant for 40 days and decreased rapidly thereafter.
      This study constitutes the beginning of an extensive quantitative analysis of the
      biochemistry of transformed endocrine cell lines in a sequestered, artificial
      tissue environment. (c) 1995 John Wiley & Sons Inc.

PMID- 18623420
TI  - Enhanced acetone-butanol fermentation using repeated fed-batch operation coupled
      with cell recycle by membrane and simultaneous removal of inhibitory products by
      adsorption.
AB  - A novel acetone-butanol production process was developed which integrates a
      repeated fed-batch fermentation with continuous product removal and cell recycle.
      The inhibitory product concentrations of the fermentation by Clostridium
      acetobutylicum were reduced by the simultaneous extraction process using
      polyvinylpyridine (PVP) as an adsorbent. Because of the reduced inhibition
      effect, a higher specific cell growth rate and thus a higher product formation
      rate was achieved. The cell recycle using membrane separation increased the total
      cell mass density and, therefore, enhanced the reactor productivity. The repeated
      fed-batchoperation overcame the drawbacks typically associated with a batch
      operation such as down times, long lag period, and the limitation on the maximum
      initial substrate concentration allowed due to the substrate inhibition. Unlike a
      continuous operation, the repeated fed-batch operation could beoperated for a
      long time at a relatively higher substrate concentration without sacrificing the
      substrate loss in the effluent. As a result, the integrated process reached 47.2
      g/L in the equivalent solvent concentration (including acetone, butanol, and
      ethanol) and 1.69 g/L . h in the fermentor productivity, on average, over a 239.5
      h period. Compared with a controlled traditional batch acetone-butanol
      fermentation, the equivalent solvent concentration and the tormentor productivity
      were increased by 140% and 320%, respectively. (c) 1995 John Wiley & Sons Inc.

PMID- 18623421
TI  - Description of two-metal biosorption equilibria by Langmuir-type models.
AB  - A biosorbent prepared from Ascophyllum nodosum seaweed biomass, FCAN2, was
      examined for its sorption capacity. Equilibrium batch sorption studies were
      performed using two-matal systems containing either (Cu + Zn), (Cu + Cd), or (Zn
      + Cd). In the evaluation of the two-metal sorption system performance, simple
      isotherm curves had to be replaced by three-dimensional sorption isotherm
      surfaces. In order to describe the isotherm surfaces mathematically, three
      Langmuir-type models were evaluated. The apparent one-parameter Langmuir constant
      (b) was used to quantify FCAN2 "affinity" for one metal in the presence of
      another one. The uptake of Zn decreased drastically when Cu or Cd were present.
      The uptake of Cd wasmuch more sensitive to the presence of Cu than to that of Zn.
      The presence of Cd and Zn alter the "affinity" of FCAN2 for Cu the least at high
      Cu equilibrium concentrations. The mathematical model of the two-metal sorption
      system enabled quantitative estimation of one-metal (bio)sorption inhibition due
      to the influence of a second metal. (c) 1995 John Wiley & Sons Inc.

PMID- 18623422
TI  - Cometabolic degradation of trichloroethylene in a bubble column bioscrubber.
AB  - A bubble column bioreactor was used as bioscrubber to carry out a feasibility
      study for the cometabolic degradation of trichloroethylene (TCE). Phenol was used
      as cosubstrate and inducer. The bioreactor was operated like a conventional
      chemostat with regard to the cosubstrate and low dilution rates were used to
      minimize the liquid outflow. TCE degradation measurements were carried out using
      superficial gas velocities between 0.47and 4.07 cm s(-1) and TCE gas phase loads
      between 0.07 and 0.40 mg L(-1) Depending on the superficial gas velocity used,
      degrees of conversion between 30% and 80% were obtained. A simplified reactor
      model using plug flow for the gas phase, mixed flow for the liquid phase, and
      pseudo first order reaction kinetics for the conversionof TCE was established.
      The model is able to give a reasonable approximation of the experimental data.
      TCE degradation at the used experimental conditions is mainly limited by reaction
      rate rather than by mass transfer rate. The model can be used to calculate the
      reactor volume and the biomass concentration for a required conversion. (c) 1995
      John Wiley & Sons Inc.

PMID- 18623423
TI  - Effects of p-cresol and chlorophenols on pentachlorophenol biodegradation.
AB  - The effects of three aromatic compounds, p-cresol, 2,4-dichlorophenol (DCP), and
      2,4,6-trichlorophenol (TCP), on cell growth and pentachlorophenol (PCP)
      degradation bya Flavobacterium species were investigated. While p-cresol was not
      degraded by this bacterium, DCP and TCP were simultaneously degraded with PCP.
      Both DCP and TCP lowered cell growth and PCP degradation rate. Cell growth was
      modeled by cell death, because p-cresol, DCP, and TCP were toxic to the organism.
      A new model was used to predict cell death rate in a mixture of two toxic
      compounds from the cell death kinetics for each individual compound. PCP
      degradation rates were modeled by conventional inhibition models, but only over a
      small concentration range for the secondary toxic compound. However, a new
      empirical model described PCP degradation over a wider concentration range of the
      secondary toxic compound. (c) 1995 John Wiley & Sons Inc.

PMID- 18623424
TI  - Recombinant cyclin E expression activates proliferation and obviates surface
      attachment of chinese hamster ovary (CHO) cells in protein-free medium.
AB  - Exogenous growth factors normally required in cell culture activate cell
      proliferation via the molecular controls of cell-cycle progression. Highly
      differing influences of mitogenic stimulation of Chinese hamster ovary (CHO)
      cells by insulin and basic fibroblast growth factor(bFGF) have been clearly
      observed in a defined protein-free medium. CHO K1 cells stimulated only with
      insulin grow with flattened cell morphology and extensive cell-cell contact,
      whereas stimulation with only bFGF or bFGF plus insulin results in loss of cell
      cell contact and a transformed and rounded-up morphology. Compared with insulin
      stimulated cells, bFGF-stimulated cells exhibit a relatively long G1, and short S
      phase, and contain higher levels of cyclin E. Observation of elevated levels of
      cyclin E in wild-type CHO K1 cells mitogenically stimulated by basic fibroblast
      growth factor motivated transfection of these cells by a cyclin E expression
      vector. These transfectants grew rapidly in protein-free basal medium and had
      similar cyclin b levels, distributions of nuclear cell-cycle times, and cell
      morphologies as bFGF-stimutated CHO K1 culture. Metabolic engineering of cell
      cycle regulation thus bypasses exogenous growth factor requirements, addressing a
      priority objective in economical, reproducible, and safe biopharmaceutical
      manufacturing. (c) 1995 John Wiley & Sons Inc.

PMID- 18623425
TI  - Purification of an L-asparaginase-atrial natriuretic peptide fusion protein
      expressed in Escherichia coli.
AB  - A novel fusion protein designed to facilitate protein purification was expressed
      in Escherichia coli and purified separately by two different chromatography
      methods. L-Asparaginase from Erwinia chrysanthemi is fused to the N-terminus of a
      model peptide, alpha-human atrial natriuretic peptide (alpha-hANP). L
      Asparaginase was chosen because of its selective affinity for L-asparagine and
      because of its unusually high isoelectric point(8.6). A gene construction without
      the L-asparaginase native signal sequence caused expression at a level of 8% of
      total cell protein, while gene construction with the native signal sequence
      resulted in over five time less expression. The hybrid protein expressed without
      the signal sequence was purified from clarified cell lysate byeither L-asparagine
      affinity chromatography or cation exchange chromatography. After digestion of the
      fusion protein with factor Xa protease, a peptide with a molecular weight
      corresponding to the theoretical molecular weight of alpha-hANP was observed by
      coupled HPLC/mass spectrometry. (c) 1995 John Wiley & Sons Inc.

PMID- 18623426
TI  - The effective diffusion coefficient and the distribution constant for small
      molecules in calcium-alginate gel beads.
AB  - The effective diffusion coefficient, D(e), and the distribution constant, K(i),
      for selected mono- and disaccharides and organic acids were determined in
      homogeneous calcium-alginate gel with and without entrapped bacteria. Results
      were obtained from transient concentration changes in well-stirred solutions of
      limited volume, in which the gel beads were suspended. The effective
      diffusioncoefficients and the distribution constants were estimated by fitting
      mathematical model predictions to the experimental data using a nonlinear model
      fitting program (MODFIT). Both single solute diffusion and multiple solute
      diffusion were performed. A small positive effect was obtained onthe values of
      D(e) for the system of multiple solute diffusion; however, the values of K(i)
      were not significantly influenced. For the nine solutes tested, D(e) for 2% Ca
      alginate gel beads was found to be approximately 85% of the diffusivity measured
      in water. The effects on D(e) and K(i), for lactose and lactic acid were
      determined for variations of alginate concentration, pH, temperature, and biomass
      content in the beads. D(e) decreased linearly for both lactose and lactic acid
      with increasing cell concentration in the Ca-alginate gel. K(i), was constant for
      both lactose and lactic acid with increasing cell concentration. D(e) was
      significantly lower at pH 4.5 than at pH 5.5 and 6.5 for both lactose and lactic
      acid. Furthermore, D(e) seemed to decrease with increased alginate concentration
      in the range of 1% to 4%. The diffusion rate increased with increasing
      temperature, and the activation energy for the diffusion process for both lactose
      and lactic acid was constant in the temperature range tested. (c) 1995 John Wiley
      & Sons Inc.

PMID- 18623429
TI  - Extraction of lysozyme and ribonuclease-a using reverse micelles: Limits to
      protein solubilization.
AB  - Experiments are reported here on the equilibrium partitioning of lysozyme and
      ribonuclease-a between aqueous and reversed micellar phases comprised of an
      anionic surfactant, sodium di-2-ethylhexyl sulfosuccinate (AOT), in isooctane. A
      distinct maximum, [P](rm,max) was found for the quantity of a given protein that
      can be solubilized in the reverse micelle phase by the phase-transfer method.
      This upper limit depended upon the size of the protein, the surfactant
      concentration, and the aqueous phase ionic strength, and was determined by
      complex formation between protein and surfactant molecules to form an insoluble
      interfacial precipitate at high values of [P](rm). In this work, it was found to
      be possible to dissociate the protein-surfactant complex and recover the
      precipitated protein. The kinetics of protein-surfactant complex formation
      depended upon the nature and concentration of the solubilized protein and on the
      surfactant concentration. Calculations of micellar occupancy and the relative
      surface areas of protein molecules and surfactant head-groups suggested that it
      was the exposure of the solubilized protein to the bulk organic solvent which
      promoted protein-surfactant complex formation as [P](rm) --> [P](rm,max). In the
      light of the experimental results and calculations described above, a mechanistic
      model is proposed to account for the observed phenomena. This is based upon the
      competing effects of increasing the solubilized protein concentration and the
      corresponding increase in the rate of protein-surfactant complex formation. The
      dynamic nature of the reverse micelles is inherent in the model, explaining the
      formation of the interfacial precipitate with time and its dependence on the
      internal phase volume of the micellar phase. Experiments on the co-partitioning
      of water and measurement ofthe AOT concentration in both phases verified the loss
      of protein, water, and surfactant from the organic phase at high values of
      [P](rm). (c) 1995 John Wiley & Sons Inc.

PMID- 18623427
TI  - Determination of effective diffusion coefficients and distribution constants in
      polysaccharide gels with non-steady-state measurements.
AB  - A non-steady-state method has been used for determining the effective diffusion
      coefficient, D(e), and a distribution constant, K(i), of small molecules in
      alginate gel beads. A mathematical model based on Pick's law and
      includingexternal film diffusion resistance describe the diffusion process.
      Criticalexperimental parameters for the estimation of D(e) and K(i), for both one
      and two-parameter methods were the initial solute concentration in the bulk
      liquid, the void fraction inthe reactor, and the experimental starting point. In
      our analysis, the two-parameter method is preferable. Incorporation of an
      estimate of the film resistance into the overall model increased the estimated
      values of D(e) significantly and improved the stability of the term over a range
      of reactor agitation rates. (c) 1995 John Wiley & Sons Inc.

PMID- 18623430
TI  - Sustained and constitutive high levels of protein production in continuous
      cultures of bacillus subtilis.
AB  - The feasibility of continuous production of proteins in chemostat cultures of
      Bacillus subtilis was investigated. An expression system consisting of the
      bacterium B. subtilis BR151 carrying plasmid p602/19 was used. The plasmid
      contains the cat (chioramphenicol acetyltrans-ferase) gene downstream of a strong
      vegetative T5 promoter. It was found that, at a dilution rate of 0.2 h(-1)
      production of relatively high levels of CAT protein (about 4% ofcellular protein)
      can be sustained. But, experiments at a higher dilution rate of 0.4 h(-1) were
      unproductive because of high acidformation and washout. Combination of low cell
      yield, which results from excessive acid formation, and low dilution rate led to
      a low volumetric CAT productivity. Our recent work with the nonrecombinant cells,
      has demonstrated that uptake of small amounts of citrate significantly reduces or
      entirelyeliminates the acid formation. This superior performance in the presence
      ofcitrate was hypothesized, based on strong experimental evidence, to be the
      result of a reduction in glycolysis flux through a sequence of events leading to
      a reduction in pyruvate kinase and phosphof- ructokinase activities, the
      regulatory enzymes of glycol-ysis. In this study, it is demonstrated that
      cofeeding of glucose and citrate substantially reduces theorganic acid formation
      and significantly increases the recombinant culture productivity. The combination
      of high specific CAT activity and cell density resulted in a total of six- to
      tenfold higher culture productivitywhen citrate and glucose were cometabolized
      than when glucose was the only carbon source. (c) 1995 John Wiley & Sons Inc.

PMID- 18623431
TI  - The role of glucose in ajmalicine production by catharanthus roseus cell
      cultures.
AB  - The role of glucose in ajmalicine production by Catharanthus roseus was
      investigated in the second stage of a two-stage batch process. Activities of
      tryptophan decar-boxylate (TDC) and anthranilate synthase (AS), two enzymes In
      the pathway leading to ajmalicine, were higher after induction with 40 g/L
      glucose than after induction with 60 or 80 g/L glucose. Experiments with
      different media containing mixtures of glucose and the nonpermeating osmotic
      agent xylose, and using an already induced culture as inoculum, revealed that a
      minimum amount of glucose is required to support ajmalicine production after
      enzyme induction. This requirement was not an osmotic effect. The relation
      between the glucose concentration and the specific ajmalicine production rate,
      q(p), was investigated in seven (fed-)batch cultures with constant glucose
      concentrations: 23, 29, 35, 53, 57, 75, and 98 g/L. In the cultures with a low
      glucose concentration (23, 29, and 35 g/L) the q(p) was 2.7-times higher than the
      cultures with 53 and 57 g/L, and almost six times higher than the cultures with a
      high glucose concentration (75 and 98 g/L). A glucose perturbation experiment
      (from 53 to 32 g/L) demonstrated that the ajmalicine production rate was adjusted
      without much delay. A kinetic equation is proposed for the relationship between
      the glucose concentration and q(p). Differences in enzyme induction and
      ajmalicine production at different glucose levels could not be explained by the
      intracellular concentrations of glucose, fructose, sucrose, or starch. (c) 1995
      John Wiley & Sons Inc.

PMID- 18623432
TI  - Surface IgG content of murine hybridomas: Direct evidence for variation of
      antibody secretion rates during the cell cycle.
AB  - Previous experiments have shown that population average surface lgG content is
      correlated with the specific antibody production rates of batch hybridoma
      cultures. Therefore, surface associated lgG content of single hybridoma cells
      might indicate antibody secretion rates of individual cells. Moreover, the
      surface lgG content should reflect the pattern of secretion rates during the cell
      cycle. To probe for lgG secretion rates during the cellcycle, a double staining
      procedure has been developed allowing simultaneousflow cytometric analysis of
      surface lgG content and DNA content of murine hybridoma cells. Crosslinking of
      the surface associated immunofluorescence with the cell by paraformaldehyde
      fixation permits subsequent DNA staining without loss of immunofluorescence. The
      optimized protocol has been used to determine the pattern of the surface lgG
      fluorescence as a function of the cell cycle position. It is highest during the
      G2+M cell cycle phase and the experimental data are in excellent agreement with
      the previously predicted secretion pattern during the cell cycle. (c) 1995 John
      Wiley & Sons Inc.

PMID- 18623433
TI  - Oxygen transfer and culture characteristics of self-immobilized Solanum aviculare
      aggregates.
AB  - Oxygen transfer characteristics of self-immobilized Solanum aviculare cells were
      measured using aggregates 3.0 to 12.5 mm in diameter. Apparent specific oxygen
      uptake rates in the absence of external boundary layers varied from 5.9 x 10(-11)
      to 8.5 x 10(-7) kg kg(-1) s(-1) dry weight, but did not decline continuously with
      increasing particle size. The effective diffusivity of oxygen in deactivated
      aggregates increased with particle diameter, varying from 5.0 x 10(-11) to 1.0 x
      10(-9) m(2) s(-1) or between 2% and 40% of the molecular diffusivity in water at
      the same temperature. Gas spaces detected in the larger aggregates were confined
      to the central core and were not distributed throughout the tissue to facilitate
      oxygen transfer. Oxygen consumption rates in the absence of diffusional
      limitations were estimated using the relationship between the observable Thiele
      modulus and effectiveness factor for zero-order reaction. The calculated results
      indicated severe oxygen limitations in the aggregates, but were inconsistent with
      the observation that relatively large S. aviculare aggregates contained a high
      fraction of viable cells and were capable ofactive growth and steroidal alkaloid
      synthesis. This work suggests that oxygen delivery is facilitated in living plant
      cell aggregates by mechanisms which depend on metabolic activity and which do not
      function in deactivated cells. (c) 1995 John Wiley & Sons Inc.

PMID- 18623434
TI  - Membrane anchored protein production from spheroid, porous, and solid
      microcarrier chinese hamster ovary cell cultures.
AB  - The influence of the microcarrier type on the performance of a controlled release
      process used to produce a recombinant glycosyl-phosphatidylinositol anchored
      protein was investigated. Chinese hamster ovary (CHO) cells expressing the human
      melanoma tumor antigen (p97) were cultured in 10% serum on Cultispher-GH porous
      microcarriers and then, for protein production, maintained in 2% serum. Cells
      were harvested every 48 h and p97 was recovered at 90 mug/mL and 40% purity.
      Harvested p97 concentrations were increased by harvestingfrom spheroid (241
      mug/mL) and smaller porous microcarrier, Cultispher-G (167 mug/mL) cultures. The
      low total cell specific p97 production of cells cultured on Cultispher-GH was due
      to necrosis of cells within the beads, decreased p97 expression of the
      immobilized cells, dilution by the liquid (up to 40% volume) associated with
      settled beads, and incomplete recovery of p97 from within the beads. Cells
      cultured on solid microcarriers, Cytodex-1, had the highest cell viability and
      cell specific p97 production, It is recommended that a two-stage cyclic
      harvesting process of cells cultured on small Cultispher-G or on Cytodex-1 beads
      would minimize protein loss and maximize cell specific protein recovery. (c) 1995
      John Wiley & Sons Inc.

PMID- 18623435
TI  - Selective adsorption of proteins to their ligands covalently immobilized onto
      microfibers.
AB  - Following ozone oxidation of polyester microfibers of 3.5 mum average diameter
      and 0.83 m(2)/g specific area, the fiber surface was subjected to graft
      polymerization of acrylic acid and subsequently immobilized with serologically
      active proteins including Staphylococcus aureus protein A, a specific antigen,
      and a specific antibody. The immobilization reaction was mediated by a
      watersoluble carbodiimide, which allowed formation of a co-valent linkage between
      the ligand proteins and the grafted poly(acrylic acid)chains. The yields of the
      immobilized ligand proteins were of the order of 1 mg/g fiber. Their binding
      affinity and capacity to respective specific proteins were studied in vitro from
      a buffered solution and serum. It was found that the specific proteins were
      selectively adsorbed with dissociation constants as low as 1x 10(-6) M,
      suggesting the adsorption to take place through highly specific protein-protein
      interaction. An addition of serum albumin did not significantly affect the
      specific binding, regardless of the ligand proteins. The binding capacity ranged
      from 1 x 10(-13) to 1x 10(-11) mol/cm(2) primarily depending on the surface
      density of the immobilized ligands and the number of their binding sites per
      molecule. (c) 1995 John Wiley & Sons Inc.

PMID- 18623436
TI  - Modeling of continuous Ph-stat stirred tank reactor with Lactococcus lactis ssp.
      lactis bv. diacetylactis immobilized in calcium alginate gel beads.
AB  - A dynamic diffusion-reaction-growth model is proposed for the study of lactic
      fermentation, the bioconversion of citric acid, and cell release in an
      immobilized cell reactor [pH-stat continuous stirred tank-reactor (CSTR)]. The
      model correctly simulates the onset of fermentation and colonization of the gel,
      followed by the steady state. External diffusion is nonlimiting and internal
      diffusion is limited by high cell densities at the periphery of the gel beads.
      Lactose-citrate cometabolism in the gel is related to the distribution of active
      included biomass within the gel and to gradients of substrates (lactose, citrate)
      and products (lactate, pH) in the beads. The utilization of lactose is limited by
      reaction, whereas that of citrate is limited by diffusion. Cell release from gel
      to the liquid medium occurs in the external spherical cap of the beads. In this
      peripheral zone viability is maintained at around 90%. (c) 1995 John Wiley & Sons
      Inc.

PMID- 18623437
TI  - Domain E of Bacillus macerans cyclodextrin glucanotransferase: An independent
      starch-binding domain.
AB  - The starch-binding domains of glucoamylase I (SBD of GA-I) from Aspergillus
      awamori and of cyclodextrin glucanotransferase (domain E of CGTase) from Bacillus
      macerans were fused to the C-terminus of beta-galactosidase (beta-gal) The
      majority of the fusion proteins produced in Escherichia coli were found as
      inclusion bodies. Active fusion proteins were purified by partial solubilization
      of the inclusion bodies with 2 M urea followed by affinity chromatography.
      Adsorption isotherms of purified fusion proteins on corn starch and cross-linked
      amylose were generated. The beta-gal fusion proteins had similar affinities for
      cross-linked amylose and corn starch but significantly different saturation
      capacities on corn starch. The adsorption and elution data from the potato starch
      column as well as the adsorption isotherms of p-gal-domain E fusion protein
      (BDE109) on corn starch and cross-linked amylose demonstrated that domain E of
      CGTase is an independent domain, which retained its starch-binding activity when
      separated from the other four (A-D) domains in CGTase. (c) 1995 John Wiley & Sons
      Inc.

PMID- 18623438
TI  - Formation of nitrifying biofilms on small suspended particles in airlift
      reactors.
AB  - For a stable and reliable operation of a BAS-reactor a high, active biomass
      concentration is required with mainly biofilm-covered carriers. The effect of
      reactor conditions on the formation of nitrifying biofilms in BAS-reactors was
      investigated in this article. A start-up strategy to obtain predominantly biofilm
      covered carriers, based on the balancing of detachment and a biomass production
      per carrier surface area, proved tp be very successful. The amount of biomass and
      the fraction of covered carrier were high and development of nitrification
      activity was fast, leading to a volumetric conversion of 5 kg(N) . m(-3) . d(-1)
      at a hydraulic retention time of 1h. A 1-week, continuous inoculation with
      suspended purely nitrifying microorganisms resulted in a swift start-up compared
      with batch addition of a small number of biofilms with some nitrification
      activity. The development of nitrifying biofilms was very similar to the
      formation of heterotrophic biofilms. In contrast to heterotrophic bio-films, the
      diameter of nitrifying biofilms increased during start-up. The detachment rate
      from nitrifying biofilms decreased with lower concentrations of bare carrier, in
      a fashion comparable with heterotrophic biofilms, but the nitrifying biofilms
      were much more robust and resistant. Standard diffusion theory combined with
      reaction kinetics are capable of predicting the activity and conversion of
      biofilms on small suspended particles. (c) 1995 John Wiley & Sons Inc.

PMID- 18623439
TI  - Fed-batch feeding and induction policies that improve foreign protein synthesis
      and stability by avoiding stress responses.
AB  - In this work, feeding policies aimed to avoid cellular stress responses as
      indicated by an increase in ATP-dependent proteolysis are tested. A set of
      experiments was carried out where glucose, IPTG (inducer), and phenylalanine
      (rate-limiting precursor) were added gradually in a fed-batch fashion. A
      significant increase in CAT activity was found compared with pulse-induction. In
      addition, there was a substantial increase in the rate of CAT synthesis as well
      as in the final specific CAT activity when phenylatanine and the inducer were
      added simultaneously. CAT degradation was confirmed through Western blotting
      analysis. Protease analysis (SDS-GPAGE) indicated lower proteolytic activity for
      the IPTG and phenylalanine fed-batch cases. GroEL immunoas-says indicated that
      amplification of stress proteins occurred upon CAT induction. This research
      impacts the yield of soluble cytoplasmic proteins in Escherichia coli and
      suggests that metabolically based induction/feeding policies are beneficial. (c)
      1995 John Wiley & Sons Inc.

PMID- 18623440
TI  - Morphology of Trichoderma reesei QM 9414 in submerged cultures.
AB  - The microscopic morphology of Trichoderma reesei QM 9414, growing in submerged
      culture, was studied by image analysis. The morphology was characterized by the
      total hyphal length, the total number of tips, the number of actively growing
      tips, and the length of the main hypha. To describe the growth of a single
      mycelium a simple model is set-up. The main features of the model are: (1)
      saturation type kinetics for the tip extension of the individual branches within
      the mycelium; and (2) random branching with a frequency function, which is
      proportional to the total hyphal length. The model is used to simulate a
      population of mycelia, where spore germination is described with a log-normal
      distribution. From the simulation of the population, the average properties of
      the mycelia, e.g., the average total hyphal length, are calculated, and by
      fitting the model to experimental data the model parameters are estimated.
      Finally, the distribution function with respect to the mycelia properties, that
      is, number of tips and total hyphal length, is calculated, and it corresponds
      well with the experimental determination of the distribution function. (c) 1995
      John Wiley & Sons Inc.

PMID- 18623442
TI  - Cross-flow ultrafiltration of proteins through asymmetric polysulfonic membranes:
      I. Retention curves and pore size distributions.
AB  - Flux and retention of 0.1%w/w aqueous solutions of several proteins [lysozyme,
      pepsin, bovine serum albumin (BSA), lipase, and gamma-globulin] with molecular
      weights of 14.6, 36, 67, 801 and 150 kDa are studied when they are tangentially
      filtered, with transmembrane pressure differences until 1 MPa and circulation
      velocities in the re-tentate loop from 0.04 to 1.98 m/s (laminar regime), through
      two asymmetric polysulfone commercial membranes (E-100 with a nominal pore size
      of 0.01 mum and E-500 with a nominal pore size of 0.04 mum). Results are analyzed
      with the film theory for the concentration-polarization phenomenon, obtaining the
      mass transfer coefficient along with the apparent and true retention coefficients
      for the cell used, as a function of the feed circulation velocity and the
      molecular weight of the solute. The standard retention curves lead to pore size
      distributions differing from the nominal ones. These differences can be
      attributed to the modifications of the membranes when they are in operational
      conditions, probably due to protein adsorption. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623443
TI  - Nonlinear estimation of specific growth rate for aerobic fermentation processes.
AB  - The specific growth rate of the biomass, a very important parameter of almost
      every fermentation process, cannot be measured directly or estimated from related
      variables, as the concentrations of biomass, substrates, or products, due to the
      lack of reliable and cheap sensors. In this article a stable adaptive estimator
      of the specific growth rate is designed for those aerobic processes where the
      measurement of the oxygen uptake rate is available on-line. This particular
      approach can be applied also for other reaction rates if the model of the process
      satisfies some very general assumptions, which make the dynamics of the measured
      reaction rate a nonlinear function only of two unknown parameters, the specific
      growth rate and its time derivative. With respect to a previous similar approach,
      the new estimator has one additional parameter and a different nonlinear
      structure. From the analysis of the dynamics of the estimation error, a tuning
      criterion is derived, by which the two different algorithms can be compared under
      similar conditions. Simulation results show a good performance of both estimators
      for various kind of processes and disturbances. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623444
TI  - Sequential adsorption of F(ab')(2) and BSA on negatively and positively charged
      polystyrene latexes.
AB  - The aim of the present work is to study the sequential adsorption of F(ab')(2)
      and bovine serum albumin (BSA) molecules adsorbed onto positively and negatively
      charged polystyrene latexes. Cationic and anionic latexes were prepared by
      emulsifier-free emulsion polymerization. Adsorptions of F(ab')(2) on both latexes
      at a low ionic strength and different pHs were performed. The cationic latex
      showed a higher adsorption of F (ab')(2) molecules over a range of pH, which
      could be due to the formation of multilayers. Sequential adsorption of anti-CRP
      F(ab')(2) and monomeric BSA were performed at two different pre-adsorbed
      F(ab')(2) amounts on both types of latex. Displacement of F(ab')(2) occurred only
      when the preadsorbed amounts were larger than a certain critical value, which
      depends on the adsorption pH. A greater displacement of larger preadsorbed
      amounts might be the result of a weaker contact between the protein molecules and
      the polystyrene surface. The displacement of F(ab')(2) previously adsorbed onto
      both latexes occurred due to pH changes, an increase of ionic strength and the
      presence of BSA molecules. The effect caused by these three factors was studied
      independently. The main factors in the desorption of F(ab')(2) on the anionic
      latex are the changes in pH and ionic strength, whereas on the cationic latex the
      desorption is mainly caused by the increase of the ionic strength and the
      presence of BSA. The colloidal stability of the immunotatex was improved by BSA
      adsorption, especially on cationic latex. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623445
TI  - The effect of oscillating dissolved oxygen concentrations on the metabolism of a
      Spodoptera frugiperda IPLB-Sf21-AE clonal isolate.
AB  - The effect of oscillating dissolved oxygen (DO) concentration on the metabolism
      of a clonal isolate of the Spodoptera frugiperda IPLB-Sf21-AE insect cell line
      was investigated. Specifically, the effect on cell growth, re- combinant protein
      synthesis, glucose and glutamine consumption, and lactate accumulation was
      determined. Prior to conducting the oscillating DO experiments, it was found that
      the DO concentration could be reduced to 15% air saturation without adversely
      affecting the growth rate. Under these conditions, glucose and glutamine became
      depleted as the maximum cell density was reached. The introduction of DO
      oscillations, that is, cycles consisting of 30 min at 15% DO followed by 30 min
      of anoxia, significantly altered cell metabolism, including inhibition of cell
      growth and recombinant protein synthesis. The effect of DO oscillations on
      glucose consumption was dependent on the experimental conditions. Glucose
      exhaustion occurred when the DO oscillations contained either an "apparent"
      anoxia period (nitrogen sparging discontinued upon reaching 0% DO) without pH
      control or a "true" anoxia period (nitrogen sparging continued throughout anoxia
      period) with pH control. Glucose consumption was significantly decreased,
      however, when the cells were exposed to a "true" anoxia period without pH
      control, that is, low pH inhibited glucose utilization. Glutamine uptake was not
      significantly affected by DO oscillations. Lactate only accumulated in the
      oscillating DO runs, a finding consistent with previous results demonstrating
      that significant lactate accumulation only occurs under DO-limited conditions.
      (c) 1995 John Wiley & Sons, Inc.

PMID- 18623446
TI  - On the use of the pH control reagent addition rate for fermentation monitoring.
AB  - The linear relation between the pH control reagent addition rate, the net
      conversion rates of metabolites, the carbon dioxide mass transfer rate and the
      feed rates is developed and shown to have the same form for batch, fed-batch, and
      continuous reactors, regardless of the number of feeds. The magnitudes of various
      biological and solution chemistry effects on the pH control reagent addition rate
      are estimated to be negligible, facilitating the use of the pH control reagent
      addition rate as a straightforward indicator of primary metabolism. Finally,
      application of the linear relation, termed the abiotic proton balance, is
      discussed for a number of fermentation processes. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623447
TI  - Taxol production in bioreactors: Kinetics of biomass accumulation, nutrient
      uptake, and taxol production by cell suspensions of Taxus baccata.
AB  - The kinetics of biomass accumulation, nutrient uptake and taxol production of
      Taxus baccata cell suspensions were examined in three bioreactor configurations,
      viz. 250-mL Erienmeyerflasks, 1-L working volume pneumatically mixed (PMB), and
      stirred tank (STB) bioreactors. Qualitatively similar kinetics were observed in
      all three bioreactor types. Biomass accumulation and specific nutrient uptake
      rates exhibited biphasic characteristics. Carbohydrate uptake and biomass
      accumulation substantially ceased when phosphate was depleted from the medium.
      Phosphate was identified as a possible growth-limiting nutrient. Taxol
      accumulated exclusively in the second phase of growth. A maximum taxol
      concentration of 1.5 mg/L was obtained in the PMB which was fivefold greater than
      that obtained in the Erienmeyer flasks and the STB, but the relative kinetics of
      taxol production was the same in all three reactor types. Biomass yields were
      calculated from the kinetic data and a stoichiometry for biomass formation was
      evaluated. The similarity of kinetics in the three bioreactor configurations
      suggests that taxol production by T. baccata cell suspensions is amenable to
      scateup. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623448
TI  - Immobilization of fungal spores by adhesion.
AB  - Immobilization of conidiospores of Phanerochaete chrysosporium by adhesion was
      investigated in static and flow conditions on flat and on porous supports.
      Reducing the electrostatic repulsion between the spores and the support by
      adsorption of polycations on the support allows a better adhesion efficiency and
      a higher density of adhering spores and does not affect germination and growth.
      Formation of spore aggregates either in the suspension (high ionic strength) or
      on the support tends to decrease the surface coverage and to give an
      inhomogeneous distribution of adhering spores due to detachment of aggregates.
      The density of spores adhering from a flowing suspension is lower as compared
      with static conditions and does not exceed about 2% of surface coverage; this is
      due to the influence of tangential forces, to the short contact time with the
      surface, and to perturbation of the hydrodynamics along the surface by the
      previously immobilized spores. Obtaining a high coverage of the support by
      immobilized spores requires the absence of a tangential motion. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623449
TI  - Use of comparative reasoning tools for evaluation of the effect of sterilization
      conditions on fermentations to produce acidic fibroblast growth factor.
AB  - The effects of various medium sterilization conditions on fermentations of a
      recombinant, acidic fibroblast growth factor (aFGF) producing Escherichia coli
      have been studied. Changes in the medium resulting from sterilization were
      monitored by pH and absorption spectra. This simple experiment provided excellent
      data for the demonstration of the usefulness of comparative reasoning tools in
      order to evaluate the effect of sterilization on fermentation performance. The
      time profiles of the main parameters (e.g., carbon dioxide evolution rate,
      dissolved oxygen, pH, and aFGF productivity) were simplified into piecewise
      contiguous linear segments, each of which was sequentially numbered. The length,
      position, and slope of each tine were then characterized. Application of the
      comparative reasoning tools confirmed that separate sterilization of the glucose
      was necessary for the success of the process, despite adding to the cost and
      complexity. The comparative data analysis also showed that scaleup with longer
      sterilization holding and cooling times would not be detrimental to aFGF
      production. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623450
TI  - Importance of spore mutants for fed-batch and continuous fermentation of Bacillus
      subtilis.
AB  - To alleviate plasmid instability and to prolong the production phase of
      subtilisin, integrable plasmid and spore mutants are used. Compared with batch
      type shake flask cultures, spore mutants' ability to produce subtilisin can be
      well pronounced in fed-batch and continuous cultures. Hence, the two culture
      methods make it possible to identify the peculiar characteristics of the spore
      mutants unobtainable in batch culture. Spore mutants can enhance subtilisin
      productivity and prolong subtilisin production time in fed-batch culture as well
      as enable us to use very low dilution rates (<0.1 h(-1)) without losing
      productivity in continuous culture, thereby improving the conversion yield of the
      nitrogen source. At 0.05 h(-1) the spollG mutant of Bacillus subtilis DB104
      (Deltanpr Deltaapr) (Em(r)) spollG (Bim(r)):: pMK101 (Cm(r)) showed a subtilisin
      yield about ten times higher than that from wild-type DB104 (Deltanpr
      Deltaapr)::pMK101 (Cm(r)). (c) 1995 John Wiley & Sons, Inc.

PMID- 18623451
TI  - Modeling biofilm accumulation and mass transport in a porous medium under high
      substrate loading.
AB  - A packed bed biofilm reactor inoculated with pure culture Pseudomonas aeruginosa
      was run under high substrate loading and constant flow rate conditions. The 3.1
      cm-diameter cylindrical reactor was 5 cm in length and packed with 1-mm glass
      beads. Daily observations of biofilm thickness, influent and effluent glucose
      substrate concentration, and effluent dissolved and total organic carbon were
      made during the 13-day experiment. Biofilm thickness appeared to rech quasi
      steady-state condition after 10 days. A published biofilm process simulation
      program (AQUASIM) was used to analyze experimental data. Comparison of observed
      and simulated variables revealed three distinct phases of biofilm accumulation
      during the experiment: an initial phase, a growth phase, and a mature biofilm
      phase. Different combinations of biofilm and mass transport process variables
      were found to be important during each phase. Biofilm detachment was highly
      correlated with shear at the biofilm surface during all three phases of biofilm
      development. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623454
TI  - Characterization of Penicillium chrysogenum physiology in submerged cultures by
      color and monochrome image analysis.
AB  - Although filamentous microorganisms are widely used in industrial fermentation
      processes, their growth and differentiation are not yet fully understood, because
      their biomass is structured, and therefore difficult to describe and to quantify.
      This lack of appropriate tools can hinder the optimization and control of the
      fermentation. A quantitative image analysis method was therefore developed for
      characterizing the physiology of the penicillin-producing mold Penicillium
      chrysogenum. This method is based on a differential staining procedure showing
      six physiological states: growing material, three differentiated states
      characterized by an increasing granulation, a highly vacuolized state, and dead
      segments having lost their cytoplasm. The image analysis software, with versions
      written for monochrome and color images, consisted of a semiautomatic binary mask
      computation step and a fully automatic segmentation step based on a fuzzy
      classification.

PMID- 18623455
TI  - Kinetic model of disaccharide oxidation by Agrobacterium tumefaciens.
AB  - Disaccharides were microbially transformed to their corresponding 3-keto
      derivatives by resting cells of Agrobacterium tumefaciens NCPPB 396. The kinetics
      and yield of this highly specific oxidation depend on several factors. The oxygen
      concentration especially has a major influence on the production of 3-keto
      derivatives and was investigated kinetically with respect to low stationary
      oxygen concentrations in solution. Experiments showed unconventional results that
      conflicted with normal Michaelis-Menten kinetics. A kinetic model was developed
      and the kinetic constants were calculated. The model and experimental data for
      sucrose, maltose, iso-maltulose (palatinose), and leucrose are in good agreement
      with each other. Initial reaction rates with different sugars using constant
      oxygen concentrations resulted in a Michaelis-Mentent type function. The complete
      kinetics, including the effect of disaccharide and oxygen concentrations, are
      presented.

PMID- 18623456
TI  - A novel method to prepare multicellular spheroids from varied cell types.
AB  - A simple method for preparing multicellular spheroids from varied cell types has
      been successfully developed by using a stepwise gradient surface in cell
      attachability or detachability. The surface was composed of poly-N
      isopropylacrylamide (PNIPAAm), a temperature responsive polymer, as a cell
      detaching component, and collagen as a cell attaching component. The surface
      functions as a culture substratum at 37 degrees C; then, when lowering the
      temperature of culture medium, the cells attached to it detach as a self
      supporting sheet. This is because PNIPAAm dissolves into the culture medium below
      the lower critical solution temperature (LCST; about 30 degrees C), but it is
      insoluble above the LCST. The detached cell sheet forms a multicellular spheroid.
      The stepwise gradient surface which consisted of six different sectors was
      prepared by exposing a surface of the PNIPAAm-collagen mixture to ultraviolet
      (UV) irradiation six times using a photomask, sliding the hole position in the
      photomask, and changing the energy of UV irradiation. This was because
      crosslinking of collagen depended on the energy of UV irradiation, then, cell
      attachability to and detachability from the surface were tightly controlled by
      changing the energy.The stepwise gradient surface allowed us to easily determine
      optimal surface conditions to obtain good cell attachment and detachment as a
      self-supporting sheet from the surface to prepare multicellular spheroids.
      According to the evaluation of the attachability and detachability of 23 cell
      types, the optimal surface condition remarkably depended on each cell type. The
      detached cells under optimal surface conditions, including fibroblasts,
      osteoblastic cells, smooth muscle cells, and measangial cells, which were very
      difficult to form spherioids using conventional methods, were able to form
      multicellular spheroids. The results clearly demonstrate that the above-described
      method for preparing multicellular spheroids can be applied to varied cell types.

PMID- 18623457
TI  - Characterization of an oligonucleotide-binding fluorescent ligand for application
      in affinity purification of dsDNA.
AB  - The fluorescent probe PO-PRO-3 was investigated as a potential ligand for the
      affinity immobilization and purification of genomic or plasmid DNA fragments.
      Affinities and mechanisms for PO-PRO-3 binding to superhelical and linearized pUC
      18 plasmid DNA were examined through measurement of binding isotherms, continuous
      variation analysis, and DNA titrations. In addition, the effects of DNA
      conformation, protein and RNA contaminants, solvent polarity, and ionic strength
      are examined with the aim of optimizing binding and elution conditions and of
      assigning limits to the range of applicability of the affinity purification.

PMID- 18623458
TI  - Implantable hollow fiber bioreactor as a potential treatment for
      hypercholesterolemia: characterization of the catalytic unit.
AB  - Previous studies have shown that the modification of low density lipoprotein
      (LDL) by the enzyme phospholipase A(2)(PLA(2))results in a reduction of
      cholesterol levels in the plasma of hypercholesterolemic rabbits, due to
      accelerated clearance of the modified LDL. In the current study, we established
      techniques and optimized the ratio of enzyme to support for the immobilization of
      PLA(2) on a polymeric support. Hollow fiber bioreactors made from
      polytetrafluoroethylene (PTFE) polymers were used to encapsulate immobilized
      PLA(2). This design was adopted to eliminate hemolysis of red blood cells by the
      enzyme. Characterization of the resulting immobilized enzyme in terms of its
      activity, Michaelis-Menten kinetic constants, and the variation of its activity
      with incubation time is presented. The enzyme activity was not significantly
      altered upon incubation at 37 degrees C in lipoprotein-deficient serum (LPDS),
      over the course of 2 months. The Michaelis-Menten kinetics constants are K(M) =
      8.9 mM, V(max) = 6434.2 for the free enzyme and K(app) (M) = 16.7 mM, V(app)
      (max) = 619.7 for the immobilized enzyme. These data suggest that a system based
      on immobilized PLA(2) in conjunction with hollow fiber bioreactors (HFBs) may be
      a good candidate for lowering LDL levels in plasma.

PMID- 18623459
TI  - Transesterification catalyzed by polystyrene-supported chymotrypsin in toluene:
      the effect of neutralization of basic or acidic groups attaching to polystyrene
      resins.
AB  - Crosslinked polystyrene resins containing a low level of either basic or acidic
      groups were used for supports of alpha-chymotrypsin (CT), which catalyzed the
      transesterification of N-acetyl-L-phenylalanine ethyl ester (AcPheOEt) with
      propanol in toluene. With a minimal amount of water, CT was sorbed to the resins,
      basic or acidic groups of which were partly or fully neutralized by several
      soluble acids or bases. With an increasing degree of neutralization of basic
      resins by free acids, the rate of disappearance of AcPheOEt was decreased,
      whereas the by-product formation of AcPheOH, due to hydrolysis, was considerably
      suppressed, compared with the ester-exchange product, AcPheOPr. The pK(a) value
      of the neutralizing acid was also important for both CT activity and reaction
      selectivity. AcPheOPr was selectively produced at a certain range of pK(a)
      values. On the other hand, the neutralization of acidic resins with free amines
      enhanced the CT activity but a strong base promoted the formation of hydrolysis
      product.

PMID- 18623460
TI  - A combined cell-cycle and metabolic model for the growth of hybridoma cells in
      steady-state continuous culture.
AB  - The Model presented in this work demonstrates the combination of cell-cycle model
      with a model describing the growth and conversion kinetics of hybridoma cells in
      a steady-state continuous culture. The cell-cycle model is based upon a
      population balance model as described by Cazzador et al. and assumes the
      existence of a cycling-and apoptotic-cell population, which together form the
      viable-cell population. In this part the fraction of apoptotic cells, the age
      distribution of the cycling and apoptotic-cell population, the mean volume and
      biomass content per cell of the cycling, apoptotic, and viable cells, and the
      specific growth and death rates of the cells are calculated. The metabolic part
      consists of a Monod-type growth equation, four elemental balances, an equation
      assuming a constant yield of ammonia on glutamine, an equation for product
      formation, and the relation of Glacken for energy production. Furthermore, a
      maintenance-energy model for the consumption of glucose and glutamine is
      introduced, which combines the approaches of Herbert and Pirt into one model in a
      way similar to Beeftink et al. For energy consumption a Pirt model is assumed.
      The model is capable of predicting trends in steady-state values of a large
      number of variables of interest like specific growth rate, specific death rate,
      viability, cell numbers, mean viable-cell volume, and concentrations and
      conversion rates of product, glucose, glutamine, lactate, and ammonia. Also the
      concentrations and conversion rates of oxygen and carbon dioxide are
      qualitatively predicted. The values of the model predictions are generally close
      to experimental data obtained from literature.

PMID- 18623461
TI  - A synthetic medium for continuous culture of the S-layer carrying Bacillus
      stearothermophilus PV 72 and studies on the influence of growth conditions on
      cell wall properties.
AB  - Bacterial cell surface layers (S-layers) which show a crystalline structure,
      defined pores, and a regular arrangement of functional groups can be used for
      production of isoporous ultrafiltration membranes and as a matrix for
      immobilization of macromolecules. S-layer-carrying cell wall fragments from
      thermophilic Bacillaceae possess an extremely thin peptidoglycan-containing layer
      with pores larger than those in the S-layer lattice. Thus, they can directly be
      used for biotechnological applications, when an S-layer protein pool is stored in
      the rigid cell wall layer which is released during cell wall preparation, forming
      an inner S-layer. In the present study, a synthetic medium for Bacillus
      stearothermophilus PV 72 was developed by applying the pulse and shift technique
      with the aim to produce cell wall fragments with before-mentioned properties by
      varying the growth conditions in continuous culture. The organism was grown at 57
      degrees C in a bioreactor with 1 L working volume equipped with exhaust gas
      analysis and connected to a PC-based process control system. Biomass
      concentration was 2.2 g/L out of 8 g/L glucose at a dilution rate of 0.3 h(-1),
      giving a biomass productivity of 0.66 g/L h. Although the organism was grown
      under different conditions, no change in peptidoglycan composition, extent of
      peptidoglycan crosslinking, and content of secondary cell wall polymers was
      observed. The amount of S-layer protein pool stored in the rigid cell wall layer
      and the autolytic activity depended mainly on the specific growth rate. Cell wall
      fragments with properties required for ultrafiltration membrane production could
      be produced by parameter settings in continuous culture.

PMID- 18623464
TI  - Announcement from the publisher.

PMID- 18623462
TI  - Comparison of hydrolysis and esterification behavior of Humicola lanuginosa and
      Rhizomucor miehei lipases in AOT-stabilized water-in-oil microemulsions: I.
      Effect of pH and water content on reaction kinetics.
AB  - Lipolase and Lipozyme are produced in large quantities (as a result of genetic
      engineering and overexpression) for the detergents market and provide a cheap
      source of highly active biocatalysts. Humicola lanuginosa lipase (HIL) and
      Rhizomucor miehei lipase (RmL) have been isolated in partially purified form from
      commercial preparations of Lipolase and Lipozyme, respectively. These lipases
      were solubilized in Aerosol-OT (AOT)-stabilized water-in-oil (w/o) microemulsions
      in n-heptane. HIL and RmL activity in these microemulsions was assayed by
      spectrophotometric measurement of the initial rate of p-nitophenyl butyrate
      hydrolysis, and by chromatographic determination of the initial rate of octyl
      decanoate synthesis from 1-octanol and decanoic acid. The hydrolytic activity of
      HIL in microemulsions measured as a function of buffer pH prior to dispersal,
      followed a sigmoidal profile with the highest activities observed at alkaline
      pHs. This broadly matches the pH-activity profile for tributyrin hydrolysis by
      Lipolase in an aqueous emulsion assay. The hydrolytic activity of RmL in the same
      microemulsions, measured as a function of pH, gave a bell-shaped profile with a
      maximum activity at pH 7.5. Again, the observed pH-activity profile was similar
      to that reported for a purified RmL in a tributyrin-based aqueous emulsion assay.
      In contrast, the esterification activity exhibited by both HIL and RmL in AOT
      microemulsions over the available range pH 6.1 to 10.4, decreases as the pH
      increases, most likely reflecting the effect of substrate ionization. The
      dependence of the hydrolytic and condensation activity of HIL on R, the mole
      ratio of water to surfactant, were similar with both profiles exhibiting a
      maximum at R = 5. The hydrolytic and esterification activities of RmL followed
      similar R-dependent profiles, but the profiles in this case exhibited a maximum
      at R = 10. The water activities at these R values were directly measured as 0.78
      and 0.9, respectively. Measured water activities were unperturbed by the presence
      of lipase at the concentrations used in these studies.

PMID- 18623465
TI  - Enzyme-mediated proteolysis of fibrous biopolymers: Dissolution front movement in
      fibrin or collagen under conditions of diffusive or convective transport.
AB  - A numerical model based on the convective-diffusive transport of reacting and
      adsorbing proteolytic enzymes within erodible fibrous biopolymers was used to
      predict lysis fronts moving across biogels such as fibrin or collagen. The fiber
      structure and the transport properties of solutes in fibrin (or collagen) were
      related to the local extent of dissolution within the dissolving structure. An
      accounting for solubilization of adsorbed species into solution from the eroding
      fiber phase provided for complete conservation of mass in reacting systems
      containing over 10 species. At conditions of fibrinolysis typical of clinical
      situations, the model accurately predicted the dynamic rate of lysis front
      movement for plasmin, urokinase, and tissue plasminogen activator (tPA)-mediated
      lysis of fibrin gels measured in vitro. However, under conditions of extremely
      fast fibrinolysis using high enzyme concentrations, fibrinolytic fronts moved
      very rapidly (>0.1 mm/mm)-faster than predicted for diffusionlimited reactions-at
      nearly constant velocity for over 2 h, indicating non-Fickian behavior. This was
      due to proteolysis-mediated retraction of dissolving fibrin fibers that resulted
      in fiber convection and front-sharpening within 3 mum of the reaction front, as
      observed by digitally enhanced microscopy. In comparing the model to fibrinolysis
      measurements using human lys(77)-plasmin, the average first order rate constant
      for non-crosslinked fibrin bond cleavage by fibrin-bound plasmin was calculated
      to be 5s(-1) assuming that 10 cleavages per fibrin monomer were required to
      solubilize each monomer. The model accurately predicted lysis front movement
      using pressure-driven permeation of plasmin or urokinase into fibrin as well as
      literature data obtained under well- mixed conditions for tPA-mediated
      fibrinolysis. This numerical formulation provides predictive capability for
      optimization of proteolytic systems which include thrombolytic therapy, wound
      healing, controlled drug release, and tissue engineering applications. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623466
TI  - Hydraulic resistance and fouling of microfilters by Candida utilis in
      fermentation broth.
AB  - The hydraulic resistance and membrane fouling effects of Candida utilis in
      fermentation broth were investigated using Millipore PVDF 0.22-mum membranes
      (GVWP and GVHP) in a stirred-cell system at 50 kPa and 700 rpm. With the various
      components of broth, spent medium, which contains colloidal particles and
      macromolecules having sizes (0.32 to 2.67 mum) comparable with the membrane pores
      (actual range 0.26 to 0.63 mum), was found to be the major contributing factor to
      the membrane fouling by broth through pore plugging. This led the spent medium to
      exhibit the highest hydraulic resistance (R(sm) of 5.8E + 12 m(-1)) and
      percentage flux loss (81.0%) when compared with either intact cells alone in
      buffer or to whole broth. Intact cells appeared to physically block and protect
      the pores without significant adhesion, because of the relatively hydrophilic
      nature of their cell walls (hydrophobicity of 5.9% at hour 36), resulting in the
      lowest hydraulic resistance (Rsbc of 7.5E + 11m(-1)) and percentage flux loss
      (19.3%).However, the hydraulic resistance and percentage flux loss of broth
      increased as cells aged. This was attributed to the increase in particle loading
      (intact cells by 15.37%, released cell contents and cell fragments) and in the
      hydrophobicity of cell walls. Autoclaved broth, lysed broth and aged broth, which
      contained a larger portion of colloidal particles and released cell contents
      caused a more pronounced fouling effect. This was revealed by the absence of flux
      recovery after depressurization with continuous stirring, even when a hydrophilic
      membrane was used. Furthermore, the hydrophobicity of C. utilis was found to
      increase with yeast extract present in medium, and use of hydrophobic membranes
      helped enhance the fouling effect. Overall, the degree of irreversible membrane
      fouling could be revealed by the value of R(sm)/R(t') and the hydraulic
      resistance, which resulted from concentration polarrzation, could be revealed by
      the value of R(c)/R(t') where R(t) = R(m) + R(sm) + R(c') and R(m) is the clean
      membrane resistance. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623467
TI  - Overexpression of bcl-2, apoptosis suppressing gene: Prolonged viable culture
      period of hybridoma and enhanced antibody production.
AB  - Human bcl-2 DNA was introduced into mouse hybridoma 2E3 cells and expressed at a
      high level by using BCMGSneo vector, which reportedly amplifies as multiple
      copies in the cells independently of their chromosomes. The high expression of
      bcl-2 in BCMGSneo-bcl-2 transfectants was confirmed by western blotting. In batch
      cultures, the overexpression of bcl-2 raised the maximum viable cell density by
      45%, delayed the initiation of apoptosis by 2 days, and prolonged the viable
      culture period by 4 days. The delayed initiation of apoptosis was detected by
      emergence of the ladder pattern on DNA electrophoresis and increase of the dead
      cell number. The bcl-2 transfectants produced lgG(1) fourfold per batch culture
      in comparison with 2E3 cells transfected with BCMGSneo but not with bcl-2: a
      little less than twofold due to the improved survival of the cells and more than
      twofold due to the enhanced lgG(1) production rate per cell of the bcl-2
      transfectants. The method to engineer hybridoma cells genetically with bcl-2
      using BCMGSneo vector for increasing viability and productivity would be widely
      applied for improving antibody productivity of hybridoma cultures. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623468
TI  - Gas phase composition effects on suspension cultures of Taxus cuspidata.
AB  - The effect of different concentrations and combinations of oxygen, carbon
      dioxide, and ethylene on cell growth and taxol production in suspension cultures
      of Taxus cuspidata was investigated using several factorial design experiments.
      Low head space oxygen concentration (10% v/v) promoted early production oftaxol.
      High carbon dioxide concentration (10% v/v) inhibited taxol production. The most
      effective gas mixture composition in terms of taxol production was 10% (v/v)
      oxygen, 0.5% (v/v) carbon dioxide, and 5 ppm ethylene. Cultures grown
      underambient concentration of oxygen had a delayed uptake of glucose and fructose
      compared to cultures grown under 10% (v/v) oxygen. Average calcium uptake rates
      into the cultured cells decreased and average phosphate uptake rates increased as
      ethylene was increased from 0 to 10 ppm. These results may indicate that gas
      composition alters partitioning of nutrients, which in turn affects secondary
      metabolite production. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623469
TI  - Immobilization and properties of carminomycin 4-O-methyltranferase, the enzyme
      which catalyzes the final step in the biosynthesis of daunorubicin in
      Streptomyces peucetius.
AB  - The carminomycin 4-O-methyltransferase enzyme from Streptomyces peucetius was
      covalently immobilized on 3M Emphaze ABI-activated beads. Optimal conditions of
      time, temperature, pH, ionic strength, enzyme, substrate (carminomycin), and
      cosubstrate (S-adenosyl-L-methionine) concentrations were defined for the
      immobilization reaction. Protein immobilization yield ranged from 52% to 60%.
      Including carminomycin during immobilization had a positive effect on the
      activity of the immobilized enzyme but a strongly negative effect on the coupling
      efficiency. The immobilized enzyme retained at least 57% of its maximum activity
      after storage at 4 degrees C for more than 4 months. The properties of the free
      and immobilized enzyme were compared to determine whether immobilization could
      alter enzyme activity. Both soluble and bound enzyme exhibited the same pH
      profile with an optimum near 8.0. Immobilization caused an approximately 50%
      decrease in the apparent K(m) (K'(m)) for carminomycin while the K'(m) for S
      adenosyl-L-methionine was approximately doubled. A 57% decrease in the V(max)
      value occurred upon immobilization. These changes are discussed in terms of
      active site modifications as a consequence of the enzyme immobilization. This
      system has a potential use in bioreactors for improving the conversion of
      carminomycin to daunorubicin. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623470
TI  - Mutant Escherichia coli penicillin acylase with enhanced stability at alkaline
      pH.
AB  - Increased stability at alkaline pH should be a valuable attribute for the
      utilization of penicillin acylase in bioreactors employed to convert penicillins
      into 6-aminopenicillanic acid, a precursor of semisynthetic penicillins. In these
      systems, base is added for pH control, which results in local alkaline conditions
      that promote enzyme inactivation. Hydrolysis and synthesis reactions are also pH
      dependent. Here, we report work in which the gene coding for Escherichia coli
      penicillin acylase was subjected to oligonucleotide-directed random mutagenesis
      at regions coding for amino acids predicted to be at the surface of the enzyme.
      The resulting mutant library, cloned in E. coli, was screened by a filter paper
      assay of the colonies for the presence of penicillin acylase activity with
      enhanced stability at alkaline pH. Characterization of one of the selected clones
      revealed the presence of a mutation, Trp431-Arg, which would presumably alter the
      surface charge of the protein. In vitro experiments demonstrated a near twofold
      increase in the half-life of the mutant enzyme when stored at pH 8.5 as compared
      with the wild-type enzyme, with a comparable specific activity at several pH
      values. In general, the mutant displayed increased stability toward the basic
      side in the pH-stability profile. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623471
TI  - Augmentation of mass transfer through electrical means for hydrogel-entrapped
      Escherichia coli cultivation.
AB  - Nutrient depletion and inhibitory end-product accumulation are the major problems
      for hydrogel-entrapment cell cultures. An electrokinetic technique was developed
      to enhance intrahydrogel mass transfer to overcome these problems. Escherichia
      coli cells (ATCC 15224) were entrapped in 3.2-mm-thick potassium-K-carrageenan
      and agarose hydrogel slabs. With a electric current density of 180A/m(2) the cell
      densities were increased by 140%(from 3.9 to 9.6 dry cell weight [DCW] g/L) in
      potassium-K-carrageenan and by 80% (from 3.9 to 7.0 DCW g/L) in agarose. A
      mathematical model taking into account nutrient depletion, inhibitory end-product
      formation, and cell growth kinetics under facultatively anaerobic conditions was
      developed to rationalize the overall transport and biological behaviors in the
      hydrogel. The cell growth in hydrogel was successfully simulated. It is concluded
      that the augmented transports for glucose and inhibitory end-products accounted
      for these increases in cell growth. The increase in cell density in potassium-K
      carrageenan was due to the enhanced removal of inhibitory end-products (through
      electroosmosis and electro-phoresis: 80%) and due to the augmented glucose
      transport (through electroosmosis: 20%). (c) 1995 John Wiley & Sons, Inc.

PMID- 18623472
TI  - Studies on the synthesis of betahCG hormone in vero cells by recombinant vaccinia
      virus.
AB  - Synthesis of the beta-subunit of human chorionic gonado-tropin (betahCG) in Vero
      cells by the recombinant vaccinia virus has been studied. The yield of betahCG
      was a function of the multiplicity of infection (MOI), and was highest at 25 MOI.
      The kinetics of synthesis and initial secretion of betahCG, deduced from the
      pulse-chase experiments were "zero order." At 30 h postinfection, the relative
      values of net synthesis and secretion rates were 4.0 AU. mm(2) betahCG/10(6)
      cells. h and 1.55 AU. mm(2) betahCG/10(6) cells. h, respectively. The time
      required to secrete 50% of intracellular betahCG was 210 min. Pulse-chase data
      also showed that 24% of betahCG was degraded intracelluiarly within 10 h, of
      which 17% was detected in the autoradiogram. Along with 30 kD betahCG, a
      satellite band of 28 kD was evident among the peptide synthesized in Vero cells.
      The molecular weight of vaccinia-derived betahCG was 13 kD more that its
      nonglycosylated form, indicating extensive glycosylation in Vero cells. The mRNA
      levels in infected Vero cells at different postinfection times were quantified by
      excess DNA dot-blot hybridization. It appears that the Vero cell possesses some
      host cell-associated factor(s), which prevented the transcription of early
      betahCG-mRNA promoted by the early signal of the vaccinia P 7.5 promoter. The
      half-life of betahCG-mRNA, as determined by follow-up of decay after blocking
      transcription initiation, was found to be 6.4 h. The synthesized betahCG was
      immunoreactive as it reacted with monoclonal and polyclonal monospecific
      antibodies. The subunit was also biologically active, as it combined with native
      betahCG to form heterodimer betahCG, which competed with (125)I-hCG for
      radioreceptors and stimulated testosterone synthesis in Leydig cells. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623473
TI  - Effects of chemical treatments and heating on the crystallinity of celluloses and
      their implications for evaluating the effect of crystallinity on cellulose
      biodegradation.
AB  - Chemical treatments similar to those routinely used to extract cellulose from
      plant biomass caused significant increases in the relative crystallinity index
      (RCI) of Sig-macell 100 (a commercial cellulose of moderate crystallinity), as
      measured by x-ray powder diffraction in both the reflectance and transmittance
      modes. In general, the largest increases in RCI were observed following higher
      (rather than lower) temperature treatments. Substantial increases in crystalliity
      were also observed upon resuspension in water prior to drying, with higher
      temperatures again resulting in the greatest increases in RCI. Measurement of the
      RCIs of wetted Sigmacell 100 samples by acid hydrolysis kinetics revealed that
      most of the increased crystallinity occurred rapidly upon contact with water. In
      contrast to Sigmacell 100, a cellulose of higher initial crystallinity (the
      microcrystalline cellulose Sigmacell 50) showed little change in crystallinity
      following the above treatments. The results provide a partial explanation for the
      inconsistent relationships reported between cellulose crystallinity and cellulose
      biodegradation. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623476
TI  - Thermodynamic and kinetic parameters of lipase-catalyzed ester hydrolysis in
      biphasic systems with varying organic solvents.
AB  - Kinetics of lipase-catalyzed hydrolysis of esters were modeled using reactant
      activities for aqueous-organic, biphasic systems. By using thermodynamic
      activities of the substrates in ordinary rate equations, the kinetic parameters
      were corrected for the contribution of substrate-solvent interactions and a
      uniform quantification of the substrates for lipase attached to the interface can
      be achieved. The kinetic parameters, on the basis of their thermodynamic
      activities, should be constant in different systems, provided that the solvents
      do not interfere with the binding of the substrates to the enzyme nor affect the
      catalytic mechanism. Experimental and computational methods on how to obtain the
      thermodynamic activities of the substrates are presented. Initial rates were
      determined for Pseudomonas cepacia lipase (PcL)-catalyzed hydrolysis of decyl
      chloroacetate in dynamic emulsions with various solvents. The thermodynamic
      equilibrium and corrected kinetic constants for this reaction appeared to be
      similar in various systems. The kinetics of PcL in an isooctane-aqueous biphasic
      system could be adequately described with the rate equation for a ping-pong
      mechanism. The observed inhibitory effect of decanol appeared to be a consequence
      of this mechanism, allowing the backreaction of the decanol with the chloroacetyl
      enzyme complex. The kinetic performance of PcL in systems with toluene, dibutyl
      ether, and methyl isobutyl ketone could be less well described. The possible
      causes for this and for the remaining differences in corrected kinetic parameters
      are discussed.

PMID- 18623477
TI  - Comparison of hydrolysis and esterification behavior of Humicola lanuginosa and
      Rhizomucor miehei lipases in AOT-stabilized water-in-oil microemulsions: II.
      Effect of temperature on reaction kinetics and general considerations of
      stability and productivity.
AB  - Humicola lanuginosa lipase (HIL) and Rhizomucor miehei lipase (RrnL), isolated
      from commercial preparations of Lipolase and Lipozyme, respectively, were
      solubilized in AOT-stabilized water-in-oil (w/o) microemulsions in n-heptane and
      aspects of their hydrolysis and condensation activity examined. The temperature
      dependence of HIL hydrolysis activity in unbuffered R = 10 microemulsions matched
      very closely that for tributyrin hydrolysis by Lipolase in an aqueous emulsion
      assay. Apparent activation energies were measured as 13 +/- 2 and 15 +/- 2 kJ mol
      / respectively. Condensation activity, however, was essentially independent of
      temperature over the range 5 degrees to 37 degrees C. The stability of HIL over a
      30-day period was very good at all pH levels (6.1, 7.2, 9.3) and R values studied
      (5, 7.5, 10, 20), except when high pHs and low R values were combined. The
      excellent stability was reflected by the linearity of the productivity profiles
      which facilitate system optimization. The temperature dependence of RmL
      hydrolysis activity toward pNPC(4) showed a maximum at 40 degrees C and an
      apparent E(act) = 20 +/- 2 kJ mol(-1) was calculated based on the linear region
      of the profile (5 degrees to 40 degrees C). RmL esterification activity showed
      only a slight dependence on temperature over the studied range (0 degrees to 40
      degrees C) and an apparent E(act) = 5 +/- 1 kJ mol(-1) was measured for octyl
      decanoate synthesis. Both RmL and HIL, therefore, have potential for application
      in low temperature biotransformations in microemulsion-based media. The stability
      of RmL over a 30-day period was good in R = 7.5 and R = 10 microemulsions
      containing pH 6.1 buffer, and this was reflected in the linearity of their
      respective productivity profiles. RmL stability was markedly poorer at more
      alkaline pH, however, and proved to be sensitive to relatively small changes in
      the R value.

PMID- 18623478
TI  - Sporulation: an alternative way to recover recombinant proteins from Bacillus
      subtilis.
AB  - A recombinant strain of Bacillus subtilis engineered for endocellular expression
      of human interleukin-1 receptor antagonist (IL-Ira) was subjected to sporulation.
      The recombinant protein was recovered from the sporulation supernatant in
      quantities, purity, and activity comparable with those obtained from a
      traditional cell lysate. Thus, exploitation of this natural mechanism of
      autolysis could overcome problems of intact protein recovery related to the cell
      disruption step.

PMID- 18623479
TI  - Real-time monitoring of protein secretion in mammalian cell fermentation:
      measurement of monoclonal antibodies using a computer-controlled HPLC system
      (BioCad/RPM).
AB  - On-line, "real-time" monitoring of product concentration is important for
      mammalian cell culture fermentation. The continuous measurement of monoclonal
      antibodies allows for instantaneous determination of cell productivity and
      effective manipulation of the fermentor operating conditions for optimal
      production. This article will present the evaluation and application of a
      BioCad/RPM system (Per Septive Biosystems) for rapid analysis of lgG
      concentration for hybridoma cell cultivation. Several commercial crossflow
      filtration devices are tested for low protein retention and fouling properties. A
      protein G column is used successfully for analyzing about 400 samples of lgG(1),
      without significant loss in separation efficiency. The Immuno Detection system is
      integrated into a computer-controlled 15-L fermentor. This fermentor could be
      operated in batch and perfusion modes with cell densities up to 20 million
      cells/mL. A continuous cell-free sample stream obtained by a hollow fiber filter
      system is introduced to the BioCad/RPM for analysis. The speed of this system
      allows for real-time monitoring even at high densities with fast dynamics. A
      murine hybridoma cell (A10G10) is cultivated in batch and continuous reactors and
      antibody concentration is measured continuously with complete sterility. The
      results are compared to offline measurements with good agreement.

PMID- 18623480
TI  - Fed-batch culture of Bacillus thuringiensis for thuringiensin production in a
      tower type bioreactor.
AB  - Fed-batch culture of Bacillus thuringiensis in a modified airlift reactor has
      been developed by using adaptive control of glucose concentration in the reactor.
      The glucose concentration was estimated via a correlation equation between carbon
      dioxide production rate and glucose consumption rate. The estimated glucose
      concentration as the output variable was fed back to computer for calculation of
      substrate addition. The modified reactor was an airlift reactor with a net draft
      tube. The airlift reactor had high oxygen transfer rate and low shear stress
      which were important factors for production of thuringiensin. Fed-batch culture
      of Bacillus thuringiensis in the modified airlift reactor provided significant
      improvement of thuringiensin production.

PMID- 18623481
TI  - Enzymatic preparation of biosurfactants from sugars or sugar alcohols and fatty
      acids in organic media under reduced pressure.
AB  - Biosurfactants were prepared by enzymatic esterification of sugars and sugar
      alcohols in nonaqueous media. Sorbitol monooleate was produced in pure molten
      substrates, with reduced pressure to remove water. The results were compared to
      synthesis in organic solvent, with and without water removal. Synthesis in
      organic solvent with water removal, obtained by refluxing through a desiccant
      under reduced pressure, proved to be the most efficient method in terms of total
      yield and side-products formation. This process was applied to the production of
      different surfactants, by changing the nature of the hydrophilic and hydrophobic
      moieties. Yields above 90% of monoesters were obtained after 24 h when the
      reaction was carried out in 2-methyl-2-butanol with Novozym 435 (Type B lipase
      from Candida antarctica) with an excess of hydroxyl donor.

PMID- 18623482
TI  - A metabolic model of the biological phosphorus removal process: I. Effect of the
      sludge retention time.
AB  - The biological phosphorus removal process is a process which depends basically on
      three internal storage compounds. Poly-beta-hydroxybutyrate (PHB) produced during
      the anaerobic phase is used as substrate for biomass, polyphosphate, and glycogen
      formation. The reaction rates of the aerobic processes are primarily determined
      by the PHB content of the cells. This PHB content is highly dynamic due to the
      conversions during the anaerobic and aerobic phase of the cycle and the ratio
      between substrate addition and biomass present in the reactor. The amount of
      biomass present in the reactor is determined by the sludge retention time and
      growth rate. A metabolic model of the biological phosphorus removal process was
      developed and verified over a wide range of growth rates. The effect of different
      growth rates on the internal fractions of stored components was determined and
      described mathematically. One set of kinetic parameters was capable of describing
      the measured conversions of all components observed in the reactor as a function
      of the sludge retention time.

PMID- 18623483
TI  - A metabolic model of the biological phosphorus removal process: II. Validation
      during start-up conditions.
AB  - A metabolic model of the biological phosphorus removal process has been developed
      and validated previously for complex conversions during the process under
      anaerobic and aerobic conditions at different growth rates in sequencing batch
      reactors in steady state. For additional validation of the metabolic model, the
      model was applied to the dynamic conditions which occur during the start-up phase
      of the biological P removal in the presence and absence of non-polyP
      heterotrophic microorganisms. In a laboratory scale sequencing batch reactor,
      experiments were performed to examine the enrichment of the population with
      polyphosphate organisms during the start-up and the subsequent shift from non
      polyP, heterotrophic organisms to polyP organisms in the sludge. The effect of
      different influent loading patterns for acetate and phosphate was studied. In
      these experiments, the maximal growth rate of the polyP organisms and the
      behavior of the internal storage compounds could be derived. The metabolic model
      was capable of describing the experimental results, without the need to adjust
      the kinetic or stoichiometric parameters obtained under steady state conditions.

PMID- 18623484
TI  - Kinetics of phase separation for polyethylene glycol-phosphate two-phase systems.
AB  - Phase separation times for polyethylene glycol (PEG)-4000-phosphate aqueous two
      phase systems were studied, for small scale (5-g) and large scale (1300-g)
      systems, as a -function of the stability ratio. Profiles of dispersion height for
      both large and small scale systems were represented as a fraction of the initial
      height and were found to be independent of the geometrical dimensions of the
      separator. Furthermore, by plotting time as a fraction of the initial height the
      total time of separation can be calculated for a given height of system at a
      particular stability ratio. This generalization is important for the design of
      large scale aqueous two-phase separators. Phase separation times were also found
      to be dependent on which of the phases is continuous. A characteristic change in
      phase separation time was also observed at the phase inversion point (i.e., where
      the dispersed phase changes to a continuous phase and vice versa) and this point
      tends toward higher volume ratios as the tie-line length (TLL) is increased.
      Furthermore, the phase inversion point at each TLL corresponds to a fixed
      phosphate concentration.

PMID- 18623485
TI  - The effect of particle morphology and concentration on the directly measured
      yield stress in filamentous suspensions.
AB  - The influence of concentration (mass and volume fraction) and particle morphology
      on the yielding properties of filamentous broths of Aspergillus niger and
      Streptomyces levoris was investigated using the rotating vane technique and
      compared with those of pulp suspensions. Two methods were applied to determine
      the volume fraction of the cells growing in filamentous form: the measurement of
      interstitial volume using a high molecular weight dye or dextran, and the
      measurement of dewatered broth filter cake volume by displacement using a
      pycnometer. The latter method provided the most reliable results. Cell
      concentrations ranging from 3 to 20 g dw/L, with corresponding volume fractions
      between 0.005 and 0.05, were obtained with broths generated in stirred tank and
      shake flask fermentations. The yield stress values obtained using the vane
      technique (0.1 <or= tau(y) <or= 37 Pa) correlated with biomass concentration (X,
      grams dry weight per liter) using the equation tau(y) = aX(b) with "b" ranging
      between 2 and 3. Increasing the length of organisms significantly increased the
      yield stress at a given cell concentration; this morphology effect was described
      using a "morphology factor" (range 0.016 to 0.11 Pa/[g dw/L](2.5)), determined by
      setting the value of "b" to 2.5. The vane yield strain, which is the critical
      strain or deformation at the yield point, was independent of cell concentration,
      but increased with increasing length of organisms. Filamentous fermentation
      broths with highly branched organisms had a greater yield stress than pulp
      suspensions.

PMID- 18623486
TI  - Hydrodynamic, physiological, and morphological characteristics of Fusarium
      moniliforme in geometrically dissimilar stirred bioreactors.
AB  - The influence of two mixing geometries (at the same scale) with different flow
      energy distributions on the performance of the gibberellic acid fermentation and
      on the morphology of the producing fungus Fusarium moniliforme was investigated.
      Fermentations were performed using a turbine mixing system (TMS) and a
      counterflow mixing system (CMS), which were high and low power number mixing
      systems, respectively. Different agitator speed rate profiles were maintained to
      obtain equal specific power inputs to both mixing systems. Substantial
      differences in morphology and productivity of F. moniliforme were found. To
      investigate the causes of these differences, local values and spectra of the
      kinetic energy of flow fluctuations were measured during the fermentations using
      a stirring intensity measuring device (SIMD) and a frequency spectrum analyzer.
      Biomass and gibberellic acid concentrations were found to be higher in the TMS,
      where the energy distribution was less even, and Vi/here the main part of the
      energy was at small frequencies (large eddies). An automated image analysis
      method was used for quantitative characterization of F. moniliforme freely
      dispersed mycelia and clump morphology. A higher proportion of clumped mycelia
      with clumps of larger area, perimeter, and roughness was observed in the TMS. A
      correlation between the morphology and productivity was found, and TMS favored
      the development of more productive mycelia with longer and thinner hyphae.
      Introduced power was not a good parameter to characterize different impellers,
      even at a given scale.

PMID- 18623487
TI  - Biomimetic-dye affinity adsorbents for enzyme purification: application to the
      one-step purification of Candida boidinii formate dehydrogenase.
AB  - Formate dehydrogenase (FDH, EC 1.2.1.2) was purified from Candida boidinii cells
      in a single step by biomimetic-dye affinity chromatography. For this purpose,
      seven' biomimetic analogues of the monochlorotriazine dye, Cibacron(R) Blue 3GA
      (CB3GA), and parent dichloro-triazine dye, Vilmafix Blue A-R (VBAR), bearing a
      car-boxylated structure as their terminal biomimetic moiety, were immobilized on
      crosslinked agarose gel, Ultrogel A6R. The corresponding new biomimetic-dye
      adsorbents, along with nonbiomimetic adsorbents bearing CB3GA and VBAR, were
      evaluated for their ability to purify FDH from extracts obtained after press
      disintegration of C. boidinii cells. Optimal conditions for maximizing specific
      activity of FDH in starting extracts (1.8 U/mg) were realized when cell growth
      was performed on 4% methanol, and press disintegration proceeded in four
      consecutive passages before the homogenate was left to stand for 1 h (4 degrees
      C). When compared to nonbiomimetic adsorbents, biomimetic adsorbents exhibited
      higher purifying ability. Furthermore, one immobilized biomimetic dye, bearing as
      its terminal biomimetic moiety mercap-topyruvic acid linked on the chlorotriazine
      ring (BM6), displayed the highest purifying ability. Adsorption equilibrium data
      which were obtained for the BM6 adsorbent in a batch system corresponded well to
      the Langmuir isotherm and, in addition, breakthrough curves were taken for
      protein and FDH adsorption in a fixed bed of BM6 adsorbent. The dissociation
      constant ( K(D)) of the complex between immobilized BM6 and FDH was found to
      equal 0.05 microM. Adsorbent BM6 was employed in the purification of FDH from a
      18-L culture of C. boidinii in a single step (60% overall yield of FDH). The
      purified FDH afforded a single-band on sodium dodecyl sulphate poly-acrylamide
      gel electrophoresis, and a specific activity of 7,0 U/mg (30 degrees C).

PMID- 18623488
TI  - Hybridoma growth and antibody production as a function of cell density and
      specific growth rate in perfusion culture.
AB  - Steady state metabolic parameters for hybridoma cell line H22 were determined
      over a wide range of cell densities and specific growth rates in a filtration
      based homogeneous perfusion reactor. Operating the reactor at perfusion rates of
      0.75, 2.0, and 2.9 day(-1)(each at four different specific growth rates), viable
      cell densities as high as 2 x 10(7) cells/mL were obtained. For the cell line
      under investigation, the specific monoclonal antibody production rate was found
      to be a strong function of the viable cell density, increasing with increasing
      cell density. In contrast, most of the substrate consumption and product
      formation rates were strong functions of the specific growth rate. Substrate
      metabolism became more efficient at high cell densities and low specific growth
      rates. The Specific rates of metabolite formation and the apparent yields of
      lactate from glucose and ammonia from glutamine decreased at low specific growth
      rates and high cell densities. While the specific oxygen consumption rate was
      independent of the specific growth rate and cell density, ATP production was more
      oxidative at lower specific growth rate and higher cell density. These observed
      shifts are strong indications of the production potential of high-density
      perfusion culture.

PMID- 18623490
TI  - Recovery and purification of bioproducts: I.

PMID- 18623491
TI  - Mechanical disruption of Escherichia coli for plasmid recovery.
AB  - Five different mechanical cell disruption processes were evaluated as methods to
      extract plasmids from bacterial cells. The methods used were sonication,
      nebulization homogenization, microfluidization, and bead milling. The recovery
      yields of intact plasmids from the various methods were measured by quantitative
      gel electrophoresis. Bead milling and microfluidization were found to have the
      highest potential for large scale extraction with total intact recoveries of over
      90% and around 50%, respectively. Other methods resulted in substantial plasmid
      degradation, with recoveries no greater than 20% of the total intact plasmid.

PMID- 18623492
TI  - Protein purification by bulk crystallization: the recovery of ovalbumin.
AB  - Crystallization is used industrially for the recovery and purification of many
      inorganic and organic materials. However, very little is reported on the
      application of bulk crystallization for proteins. In this work, ovalbumin was
      selected as a model protein to investigate the feasibility of using bulk
      crystallization for the recovery and purification of proteins. A stirred 1-L
      seeded batch crystallizer was used to obtain the crystal growth kinetics of
      ovalbumin in ammonium sulfate solutions at 30 degrees C. The width of the
      metastable region, in which crystal growth can occur without any nucleation, is
      equivalent to a relative supersaturation of about 20. The bulk crystallizations
      were undertaken within this range (using initial relative supersaturations less
      than 10) and nucleation was not observed. The ovalbumin concentration in solution
      was measured by UV absorbance and checked by crystal content measurement. Crystal
      size distributions were measured both by using a Malvern Mastersizer and by
      counting crystals through a microscope. The crystal growth rate was found to have
      a second-order dependence upon the ovalbumin supersaturation. While there is no
      discernible effect of ammonium sulfate concentration at pH 4.90, there is a
      slight effect at higher pH values. Overall the effect of ammonium sulfate
      concentration is small compared to the effect of pH, for which there is a 10-fold
      increase in the growth rate constant, k(Gsigma) over the range pH 4.6-5.4. To
      demonstrate the degree of purification which can be achieved by bulk
      crystallization, ovalbumin was crystallized from a solution containing conalbumin
      (80,000 Da) and lysozyme (14, 600 Da). After one crystallization and a crystal
      wash, ovalbumin crystals were produced with a protein purity greater than 99%. No
      contamination by the other proteins was observed when using overloaded sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) stained with
      Coomassie blue stain and only trace amounts of lysozyme were observed using a
      silver stain. The presence of these other proteins in solution did not effect the
      crystal growth rate constant, k(Gsigma). The study demonstrates the feasibility
      of using bulk crystallization for the recovery and purification of ovalbumin. It
      should be readily applicable to other protein systems.

PMID- 18623493
TI  - Metal affinity protein precipitation: effects of mixing, protein concentration,
      and modifiers on protein fractionation.
AB  - Previous work by us and others has shown that mixing impacts apparent protein
      solubility in single protein precipitations. In this work, we probe the effects
      of contacting conditions on fractional precipitation behavior at the bench scale.
      We have chosen metal affinity precipitation as our model system; the kinetics of
      this mode of precipitation are very rapid and largely irreversible and,
      consequently, mixing conditions govern the extent of fractionation and purity of
      the product in such a process. Our experimental strategy involved a three-pronged
      approach to control the effects contacting conditions on precipitate yield,
      purity, and particle size distribution. First, we studied the impact of process
      variables that control precipitant concentrations in the reactor including
      impeller speed and precipitant addition rate. Second, we controlled the rate of
      precipitation by changing the initial protein concentration to alter the protein
      protein collision rate. Third, we examined the role of the molecular-level
      kinetics of affinity precipitation by using modifiers that compete with surface
      moieties to bind the metal ion, thereby reducing its availability. Our model
      process and protein system consisted of zinc precipitations of mixtures of bovine
      serum albumin and bovine gamma-globulins, carried out at a nominal 1-L scale;
      glycine was examined as a modifier. Faster impeller speeds and lower precipitant
      addition rates increased the desired protein yields, decreased purities, and
      reduced average precipitate particle size. Higher initial protein concentrations
      were found to produce precipitates with higher yields, lower purities and
      diminished particle size. Experiments with glycine indicated that modifiers in
      the precipitant solution serve to increase product purity, decrease yield, and
      increase the average particle size in bench-scale precipitations.

PMID- 18623494
TI  - Novel function of guanidine hydrochloride in reverse micellar extraction of
      lysozyme from chicken egg white.
AB  - The efficiency of guanidine hydrochloride (GuHCl) addition in the suppression of
      gel formation and the extraction of lysozyme during reverse micellar extraction
      from chicken egg white was investigated. A low concentration of GuHCl in the feed
      permitted the successful extraction of lysozyme in its native form without gel
      formation, which is perceived as a novel function of GuHCl. The highest recovery
      and specific activity of lysozyme were obtained at a GuHCl concentration of 0.06
      M in 25 mM AOT reverse micellar extraction from 20-fold-diluted natural chicken
      egg white. Lysozyme and ovalbumin CD spectra in the corresponding GuHCl aqueous
      solutions revealed no changes in the higher order structures of the proteins.
      Furthermore, the specific activity of lysozyme in the feed was well preserved in
      the GuHCl system.

PMID- 18623495
TI  - Expanded bed affinity chromatography of dehydrogenases from bakers' yeast using
      dye-ligand perfluoropolymer supports.
AB  - Malate dehydrogenase (MDH) and glucose 6-phosphate dehydrogenase (G6PDH) have
      been partially purified from preparations of homogenized yeast cells using
      Procion Yellow H-E3G and Procion Red H-E7B, respectively, immobilized on solid
      perfluoropolymer supports in an expanded bed. A series of pilot experiments were
      carried out in small packed beds using clarified homogenate to determine the
      optimal elution conditions for both MDH and G6PDH. Selective elution of MDH using
      NADH was effective but the yields obtained were dependent on the concentration of
      NADH used. Selective elution was found to be most effective when a low
      concentration of NaCl (0.1 M) was present. MDH could be recovered in 84% yield
      with a purification factor of 94 when this strategy was adopted. In the case of
      G6PDH, specific elution using NADP(+) was successful in purifying G6PDH 178-fold
      in 96% yield. The dynamic capacity of both affinity supports was estimated by
      frontal analysis, in an expanded bed with unclarified homogenate, and
      corresponded to 17 U MDH/mL of settled Procion Yellow H-E3G perfluoropolymer
      support and 7.7 U H6PDH/mL of settled Procion Red H-E7B perfluoropolymer support.
      Expanded bed affinity chromatography of MDH resulted in an eluted fraction
      containing 89% of the applied activity with a purification factor of 113.
      Expanded bed affinity chromatography of G6PDH resulted in an eluted fraction
      containing 84% of the applied activity with a purification factor of 172. With
      both enzymes, the overall recovery of enzyme activity was greater than 94%,
      showing that the expanded bed approach to purification was nondenaturing.

PMID- 18623496
TI  - Development of an expanded bed technique for an affinity purification of G6PDH
      from unclarified yeast cell homogenates.
AB  - The use of an expanded bed of STREAMLINE Red H-7B for the purification of the
      intracellular glycolytic enzyme glucose 6-phosphate dehydrogenase (G6PDH)
      directly from untreated preparations of disrupted yeast cells has been
      investigated. Small-scale experiments, carried out in packed beds, have shown
      that the optimal pH for adsorption is 6.0 and have enabled optimization of
      elution conditions using a series of eluents. The dynamic capacity of the
      adsorbent for G6PDH was determined in a small expanded bed to be 28 units/mL.
      These results were used to develop a preparative scale separation of G6PDH in a
      STREAMLINE 50 expanded bed column. G6PDH was purified directly from an
      unclarified yeast homogenate in 99% yield with an average purification factor in
      the eluted fraction of 103. Cleaning-in-place (CIP) procedures using 0.5 M NaOH
      and 4M urea in 60% (v/v) ethanol have demonstrated that the adsorbent can be
      regenerated with no loss of adsorption capacity of alteration of bed expansion
      characteristics after many cycles of operation.

PMID- 18623497
TI  - Hydrodynamics and performance in fluidized bed adsorption.
AB  - The performance of fluidized bed adsorption is strongly influenced by the
      hydrodynamics of the fluidization process. Especially axial mixing in the liquid
      and solid phase may lead to reduced capacity and resolution. In this article
      axial mixing in the liquid phase of a classified fluidized bed based on porous
      glass granules is presented. Axial mixing was analyzed by measurements of
      residence time distributions in a fluidized bed, showing a reduction of mixing at
      increased ratio of bed height to diameter as well as at increased linear velocity
      of the liquid stream. These results were transferred to two real adsorption
      systems on two different scales: In a bench scale (up to 15 mL of adsorbent) the
      purification of monoclonal antibodies from hybridoma supernatant was performed
      with a cation exchanger, in a larger scale (up to 750 mL of matrix) the
      adsorption of bovine serum albumin (BSA) on the same matrix was investigated. The
      results showed an increase of capacity at increased bed height-to-diameter ratio;
      with regard to linear velocity a broad range of only slightly changed capacity
      was found. A shift from dispersion controlled to diffusion controlled adsorption
      at intermediate linear velocity was proposed by isolating the effect of pore
      diffusion from the effect of dispersion.

PMID- 18623498
TI  - Microfiltration of yeast suspensions with self-cleaning spiral vortices:
      possibilities for a new membrane module design.
AB  - A novel method of producing controlled vortices was used to reduce both
      concentration polarization and membrane fouling during microfiltration of
      Saccharomyces cerevisiae broth suspensions. The method involves flow around a
      curved channel at a sufficient rate so as to produce centrifugal instabilities
      (called Dean vortices). These vortices depolarize the build-up of suspended
      particles such as yeast cells at the membrane-solution interface and allow for
      increased membrane permeation rates. Various operating conditions under which
      such vortices effectively reduced cake build-up of suspended particles such as
      yeast cells at the membrane-solution interface and allow for increased membrane
      permeation rates. Various operating conditions under which such vortices
      effectively reduced cake build-up during microfiltration of 0 to 0.55 dry wt%
      yeast broth were investigated. Flux improvements of over 60% for 0.25 dry wt%
      yeast broth for flow with over that without Dean vortices were observed. This
      beneficial effect increased with increasing retentate flow rate and increasing
      transmembrane pressure and decreased with increasing concentration of suspended
      matter. Similar behavior was observed whether the cells were viable of killed.
      the improvement in flux in the presence over that in the absence of vortices
      correlated well with centrifugal force or azimuthal velocity squared. The
      relative cake resistances increased with reservoir yeast concentration. These
      values with vortices increased from 62% to 75% of that without vortices with
      increasing yeast concentration. The ratio of the cake thicknesses in the limiting
      case (at high feed concentration) was 3.25. These results suggest that self
      cleaning spiral vortices could be effective in maintaining good and steady
      microfiltration performance with cell suspensions other than those tested.

PMID- 18623499
TI  - Microfiltration of recombinant yeast cells using a rotating disk dynamic
      filtration system.
AB  - To develop a highly efficient cell harvest step under time constraint, a novel
      rotating disk dynamic filtration system was studied on the laboratory scale
      (0.147-ft.(2) nylon membrane) for concentrating recombinant yeast cells
      containing an intracellular product. The existing cross-flow microfiltration
      method yielded pseudo-steady state flux values below 25 LMH (L/m(2). h) even at
      low membrane loadings (10 L/ft.(2)). By creating high shear rates (up to 120,000(
      1)) on the membrane surface using a rotating solid disk, this dynamic filter has
      demonstrated dramatically improved performance, presumably due to minimal cake
      buildup and reduced membrane fouling. Among the many factors investigated, disk
      rotating speed, which determines shear rates and flow patterns, was found to be
      the most important adjustable parameter. Our experimental results have shown that
      the flux increases with disk rotating speed, increases with transmembrane
      pressure at higher cell concentrations, and can be sustained at high levels under
      constant flux mode. At a certain membrane loading level, there was a critical
      speed below which it behaved similarly to a flat sheet system with equivalent
      shear. Average flux greater than 200 LMH has been demonstrated at 37-L/ft.(2)
      loading at maximum speed to complete sixfold concentration and 15-volume
      diafiltration for less than 100 min. An order of magnitude improvement over the
      crossflow microfiltration control was projected for large scale production. This
      superior performance, however, would be achieved at the expense of additional
      power input and heat dissipation, especially when cell concentration reaches
      above 80 g dry cell weight (DCW)/L. Although a positive linear relationship
      between power input and dynamic flux at a certain concentration factor has been
      established, high cell density associated with high viscosity impacted adversely
      on effective average shear rates and, eventually, severe membrane fouling, rather
      than cake formation, would limit the performance of this novel system.

PMID- 18623500
TI  - Recovery of insect cells using hollow fiber microfiltration.
AB  - An efficient method was developed for media separation and cell collection for
      eukaryotic cells growing in suspension. The method is based on tangential flow
      microfiltration using an open channel arrangement in a hollow fiber
      configuration. Best results (highest processing flux rate) for polysulfone hollow
      fibers were obtained using fibers with internal diameter of 0.75 mm, 0.45 microm
      pore size, and a cell suspension flow at a shear rate of 14000 s(-1) (0.032 L/min
      per fiber). A flux rate of 500 L/m(2) h can be obtained by maintaining the
      surface area/cell ratio at 0.05 m(2)/10 L of cells at a concentration of 2.5 x
      10(6) cells/mL. Forty liters of infected insect cells can be concentrated 10
      times in 20 min without affecting cell viability.

PMID- 18623501
TI  - Protein fractionation using electrostatic interactions in membranel filtration.
AB  - One of the critical factors limiting the development of membrane systems for
      protein fractionation has been the poor selectivity that has generally been
      obtained with these membrane devices. We have demonstrated that it is possible to
      dramatically improve the selectivity of available membrane systems by exploiting
      the different electrostatic interactions between the two proteins and the
      membrane. The separation factor for the albumin-hemoglobin system could be
      increased to more than 70 simply by reducing the salt concentration and adjusting
      the pH to around 7 (near the isoelectric point of hemoglobin). This very high
      selectivity was a direct result of the strong electrostatic exclusion of the
      charged albumin from the membrane pores under these conditions. This high
      selectivity makes it possible to very effectively separate these albumin
      hemoglobin mixtures using membrane filtration, and this was demonstrated
      experimentally using both a simple batch filtration process and a continuous
      diafiltration system. The hemoglobin recovery in the diafiltration experiment was
      greater than 70% after a 3-diavolume filtration, with the Hb purification factor
      being around 100 under these conditions. These results clearly demonstrate the
      potential of membrane systems for the fractionation of proteins even with very
      similar molecular weights.

PMID- 18623502
TI  - Protein A immunoaffinity hollow fiber membranes for immunoglobulin G
      purification: experimental characterization.
AB  - Immunoaffinity adsorption is increasingly used for protein purification and
      medical applications. Synthetic membranes have advantages as support matrices in
      comparison to conventional bead supports because they are not compressible and
      they eliminate internal diffusion limitations. The goal of this study was to
      explore in detail the performance of microporous hollow fibers composed of
      modified polysulfone to which protein A was immobilized for adsorption of human
      IgG. The internal matrix was characterized by scanning electron microscopy. The
      binding equilibrium constant was measured using both static and dynamic methods.
      Break-through curves up to ligand saturation were measured and used to study the
      effects of IgG concentration, presence of contaminant albumin, flow direction,
      flow mode, and especially filtrate flow rate and maximum IgG binding capacity.
      The highest binding capacities studied were comparable with that attainable with
      bead matrices. All of the breakthrough curves could be represented on a single
      figure when plotted versus the dimensionless relative throughput (the mass of IgG
      loaded on the membrane divided by the mass that would be bound when the entire
      fiber is in equilibrium with the feed concentration), and the effect of operating
      variables on the position and shape of the individual breakthrough curves could
      be understood in terms of a dimensional performance parameter (the product of
      membrane volume and maximum binding capacity divided by the filtrate flow rate).
      The best breakthrough curves were obtained with the highest values of the
      performance parameter. Based on the results, membranes as solid supports for
      immunoadsorption can be a useful alternative to the use of traditional columns
      for protein separations.

PMID- 18623504
TI  - Preface.

PMID- 18623505
TI  - Notice to authors of new manuscripts.

PMID- 18623506
TI  - Review: Selective ligand-exchange adsorbents prepared by template polymerization.
AB  - Highly selective ligand-exchange absorbents have been prepared by template
      polymerization, a process in which the target molecule serves as a template for
      assembly of specific recognition sites. In an effort to develop materials
      suitable for chromatographic separations, thin coatings of the selctive templated
      polymers have been grafted to two reactive macroporous supports,
      poly(trimethylolpropane trimethacrylate) (TRIM), and propylmethacrylate
      derivatized silica beads. The precursor polymer prepared from the trifunctioal
      TRIM monomer is macroporous and highly crosslinked, providing a stable structure
      for surface grafting. The TRIM precursor polymer and various surface-grafted
      copolymers have been characterized by scanning electron microscopy (SEM) and IR,
      (13)C NMR, and XPS spectroscopic techniques. Composite adsorbents have also been
      prepared using propylmethacrylate-modified silica particles. While equilibrium
      rebinding selectivites for both types of surface-templated materials are similar
      to those reported previously for bulk-polymerized template polymers, the
      composite materials are far better suited to chromatographic separatios. Highly
      similar bis-imidazole substrates can be separated by ligand-exchange
      chromatography on these new templated adsorbents. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623507
TI  - Review: Multipoint binding and heterogeneity in immobilized metal affinity
      chromatography.
AB  - Studies carried out using engineered proteins clearly demonstrate that adsorption
      to derivatized surfaces involves multiple interactions between functional groups
      on the protein and complementary sites distributed on the surface. The fact that
      adsorption involves multipoint interactions has important implications for the
      design of separations processes and for the interpretation of heterogeneity in
      biological recognition phenomena. Increasing the density of surface metal sites
      (immobilized copper ions) is found to be functionally equivalent to increasing
      the number of metal-coordinating groups on the protein (histidines and
      deporotonated amines), m in that both processes increase the likelihood of
      simultaneous interactions between the protein and the surface. A consequence of
      multiple-site interactions is a significant in crease in protein binding affinity
      that depends on the arrangement of surface sites. A protein will show the highest
      affinity for arrangements of surface sites which best match its own pattern of
      functioal groups and will show lower affinity for less optimal arrangements,
      resulting in binding that is inherently heterogeneous. We have found that
      reversible protein adsorption in immobilized metal affinity chromatography (IMAC)
      is described by the Temikin model, which characterizes binding heterogeneity by a
      uniform distribution of binding energies over the population of surface binding
      sites. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623508
TI  - Plate height determination for gradient elution chromatography of proteins.
AB  - A method for determining the plate height HETP from the elution curve obtained by
      the linear gradient elution (LGE) ion-exchange chromatography (IEC) of proteins
      is presented. The method was developed on the basis of the numerical solutions of
      a chromatography model which considers the zone sharpening and the distribution
      coefficient as a function of the salt concentration. The plate height HETP is
      determined from the peak width and the salt concentration at which the peak is
      eluted in LGE. The method was applied to the experimental results with various
      ion-exchange chromatography media. A calculation example based onthe present
      method is presented to show how the chromatographic and operating parameters
      should be tuned to obtain a desired resolution. A simplified calculation
      procedure for the peak profile is also described. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623509
TI  - Protected amino acids as novel low-molecular-weight displacers in cation-exchange
      displacement chromatography.
AB  - Although the ability to carry out simultaneous concentration and purification in
      a single displacement step has significant advantages for downstream processing
      of pharmaceuticals, a major impediment to the implementation of displacement
      chromatography has been the lack of suitable displacer compounds. An important
      recent advance in the state of the art of displacement chromatography has been
      the discovery that low-molecular-weight dendritic polymers can be successfully
      employed as displacers for protein purification in ion-exchange systems. In this
      article, protected amino acid esters (based on arginine and lysine) are shown to
      be useful displacers for protein purification in cation-exchange systems. A
      dynamic affinity plot is employed to evaluate the affinity of these low-molecular
      weight compounds under dis-placement conditions. In contrast to large
      polyelectroyte displacers, the efficacy of these low-molecular-weight displacers
      was shown to be dependent on both the initial carrier salt concentration and the
      displacer concentration. In addition to the funcamental interest generated by low
      molecular-weight displacers, it is likely that these displacers will have
      significant operatioal advantages as compared with large polyelectrolyte
      displacers. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623510
TI  - Countercurrent gradient chromatography: A continuous focusing technique.
AB  - The continuous separation of proteins was performed in a countercurrent gradient
      chromatography (CGC) system. A magnetically stabilized fluidized bed (MSFB) was
      used to establish true countercurrent contact of a solid resin with a liquid
      buffer. STable pH gradients were formed in the system in less than 10 min and
      remained stable throughout the course of the separation experiment (>2 h). The
      shape of the pH gradient, which ultimately controls the resolution and purity of
      the separation, can be controlled by making simple adjustments in the
      interstitial velocities of the liquid and solid phases. We have performed the
      separation of myoglobin and human serum albumin (HSA) using this device and
      achieved concentration factors of 1.75 for myoglobin and 1.2 for HSA. A
      mathematical model that has no adjustable parameters has been developed that
      predicts the focusing behaviour and capabilities of the CGC system. Using the
      model, we have estimated the optimum phase velocities, particle diameters, and
      equilibrium parameters necessary for achieving high purity and high
      concentrations. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623511
TI  - "Molded" rods of macroporous polymer for preparative separations of biological
      products.
AB  - A continuous rod of porous poly(glycidy1 methacrylate-co-ethylene dimethacrylate)
      has been prepared by a free radical polymerization within the confines of a 16-mm
      i.d. glass column. The epoxide groups of the rod have been modified in situ by
      their reaction with diethylamine to afford the ionizable weak base 1-N,N
      diethylamino-2-hydroxypropyl functionalities that are required for the ion
      exchange chromatographic mode. The bimodal pore size distribution curve typical
      for other molded separation media also prevail for the preparative-size rod. The
      column has been used successfully for the chromatographic separation of a mixture
      of standard proteins and yeast enzymes. The column exhibits a dynamic capacity
      that exceeds 420 mg of bovine serum albumin at a flow velocity of 60 cm/h. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623512
TI  - Review: Protein refolding and inactivation during bioseparation: Bioprocessing
      implications.
AB  - The recombinant production of proteins leads to inclusion bodies which contain
      aggregated proteins in active, partially active, and inactive conformational
      states. These aggregated proteins must be extracted from the inclusion bodies,
      unfolded, and carefully refolded to the active and the stable conformational
      state. Mechanistic models for protein refolding are briefly presented. Different
      strategies and protocols are presented that lead to the active and stable protein
      conformational state. The techniques presented include chaperonin-assisted
      refolding, amino acid substitution, polyethylene glycolassisted refolding,
      protein refolding in reverse micelles, and antibody-assisted refolding of
      proteins. The techniques presented together provide a reasonable framework of the
      state-of-the-art and may be carefully applied to the bioseparation of other
      proteins and biological macromolecules of interest. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623513
TI  - Chemical instability of protein pharmaceuticals: Mechanisms of oxidation and
      strategies for stabilization.
AB  - Oxidation is one of the major chemical degradation pathways for protein
      pharmaceuticals. Methionine, cysteine, histidine, tryptophan, and tyrosine are
      the amino acid residues most susceptible to oxidation due to their high
      reactivity with various reactive oxygen species. Oxidation during protein
      processing and storage can be induced by contaminating oxidants, catalyzed by the
      presence of transition metal ions and induced by light. Oxidative modification
      depends on the structural features of the proteins as well as the particular
      oxidation mechanisms inherent in various oxidative species, and may also be
      influenced by pH, temperature, and buffer composition. Protein oxidation may
      result in loss of biological activity and other undesirable pharmaceutical
      consequences. Strategies to stabilize proteins against oxidation can be
      classified into intrinsic methods (site-directed mutagenesis and chemical
      modification), physical methods (solid vs. liquid formulations) and use of
      chemical additives. The optimum choice of chemical additives needs to be
      evaluated on the basis of the specific oxidation mechanism. Oxidation induced by
      the presence of oxidants in the system is referred to as a non-site-specific
      mechanism. Under such conditions, oxidation can be effectively inhibited by the
      appropriate addition of antioxidants or free radical scavengers. metal-catalyzed
      oxidation is a site-specific process, in which the addition of antioxidants may
      accelerate the oxidation reaction. Careful screening of chelating agents has been
      shown to be an alternative method for preventing metal-catalyzed oxidation. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623514
TI  - The Use of RP-HPLC for measuring activation and cleavage of rFVIIa during
      purification.
AB  - A reverse phase HPLC (RP-HPLC) method for analysis of recombinant factor VIIa
      (rFVIIa) has been developed. The method discriminates between different forms of
      recombinant FVII (rFVII). To obtain separation of these closely related molecules
      the method has been optimized with respect to gradient profile and temperature.
      The method has been used for optimization of purification processes and for
      kinetic studies. EVidence for autolytic cleavage was obtained. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623515
TI  - Approaches for increasing the solution stability of proteins.
AB  - Stabilization of proteins through proper formulation is an important challenge
      for the pharmaceutical industry. Two approaches for stabilization of proteins in
      solution are discussed. First, work describing the effect of additives on the
      thermally induced denaturation and aggregation of low molecular weight urokinase
      is presented. The effects of these additives can be explained by preferential
      exclusion of the solute from the protein, leading to increased thermal stability
      with respect to denaturation. Diminished denaturation leads to reduced levels of
      aggregation. The second approach involves stoichiometric replacement of polar
      counter ions (e.g., chloride, acetate, etc.) with anionic detergents, in a
      process termed hydrophobic ion pairing (HIP). The HIP complexes of proteins have
      increased solubility in organic solvents. In these organic solvents, where the
      water content is limited, the thermal denautration temperatures greatly exceed
      those observed in aqueous solution. In addition, it is possible to use HIP to
      selectively precipitate basic proteins from formulations that contain large
      amounts of stabilizers, such as human serum albumin (HSA), with a selectivity
      greater than 2000-fold. This has been demonstrated for various mixtures of HSA
      and interleukin-4. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623516
TI  - Development of surface swabbing procedures for a cleaning validation program in a
      biopharmaceutical manufacturing facility.
AB  - Validation of direct surface swabbing procedure in conjuction with total organic
      carbon (TOC) analysis is described for a biopharmaceutical product manufacturing
      operation. The swabbing technique was found to be very effective in reliably
      detecting very low levels of residuals for diverse process streams (limit of
      detection of approximately 0.5microg/cm(2)). However, contaminant recovery was
      significantly dependent on both the type of contaminant and the processing
      surface. This study serves as a guide for designing effective cleaning validation
      protocols based on direct surface swabbing techniques. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623517
TI  - Purification of a pyrogen-free human growth hormone antagonist.
AB  - Human growth hormone (hGH) is a polypeptide with 191 amino acids and a molecular
      mass of 22 kilodaltons. With the aid of computer molecular simulation, an hGH
      analog was created by altering an hGH gene to reflect the change of one amino
      acid (glycine [G] 120 to arginine [R]) within the third alpha-helix of the hGH
      molecule. This hGH analog, named hGHG120R, was found to be an hGH antagonist. It
      may have important implications in treating human conditions in which hGH levels
      are abnormally high, as found in type I diabetics. Several hundred milligrams of
      purified hGHG120R were needed to determine the biological activity of the
      antagonist in animal models. A multistep downstream process was developed to
      purify hGHG120R from cultured mouse L cells transfected with the hGHG120R gene.
      The process consisted of cell clarification, salt precipitation, membrane
      ultrafiltration, reversed phase high performance liquid chromatography, phase
      separation, and lyophiliation. This work discusses the rationale for the design
      of the process and experimental results on the purification of hGHG120R using the
      process. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623518
TI  - Computer-aided process analysis and economic evaluation for biosynthetic human
      insulin production-A case study.
AB  - Human insulin was the first mammalian protein produced in bacteria using
      recombinant DNA technology. Two technologies were developed; the first based on
      the separate expression of precursors of chains A and B of insulin, and the
      second based on the expression of a precursor of proinsulin as a Trp-E fusion
      protein. Both technologies utilized Escherichia coli as an expression system.
      Later, a third technology was developed based on a strain of yeast that can
      secrete a precursor of insulin. The second E. coli process, a variation of which
      has been commercialized by Eli Lilly and Co., is analyzed in this article from a
      process design and economic evaluation viewpoint. The objective of this work is
      to elucidate the technical complexity and high cost associated with the
      manufacturing of biopharmaceuticals. Human insulin is a good example of a protein
      based biopharmaceutical produced in large quantities (a fex tons per year) that
      requires large scale equipment and presents a multitude of scale-up challenges.
      Based onthe analysis, a number of conclusions are drawn regarding the cost
      breakdown and cost dependency on process parameters. Recommendations are made for
      cost reduction and environmental impact minimization. This analysis was performed
      using a software tool for computer-aided bioprocess design. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623519
TI  - Large scale purification of myo-inositol monophosphate phosphatase from porcine
      brains.
AB  - myo-Inositol monophosphate phosphatase (IMPase) has been purified 888-fold to
      apparent homogeneity from procine brains. The purification procedure involves:
      homogenization, ammonium sulfate fractionation, and a number of ion-exchange and
      gel-filtration chromatography steps. The purified enzyme exhibited a final
      specific activity of 932 nmol . min(-1) . mg(-1). The molecular mass of the
      enzyme was estimated to be 29kDa by SDS poly-acrylamide gel electrophoresis and
      58 +/- 5 kDa by HPLC gel filtration in 10mM Tris-HCI, pH 7.4. Kinetic
      measurements have shown that the apparent K(m) value of the phosphatase for the
      utilization of inositol-1-phosphate and beta-glycerol phosphate are 3.20 x 10(-4)
      and 8 x 10(-3) M, respectively. Similar to the same enzyme isolated from bovine
      brains, the porcine brain enzyme has been shown to be inhibited by lithium. The
      K(1) was determined to be 6.38 x 10(-4) M and the inhibition is uncompetitive.
      (c) 1995 John Wiley & Sons, Inc.

PMID- 18623520
TI  - Fermentation and isolation of C10-deacetylase for the production of 10
      deacetylbaccatin III from baccatin III.
AB  - 10-Deacetylabaccatin III (10 DAB), an important precursor for paclitaxel
      semisynthesis, is enhanced in yew extracts using C10-deacetylase and C13
      deacylase enzymes.(4) C10-deacetylase is an intracellular enzyme produced by the
      fermentation of a soil microorganism, Nocardioides luteus (SC 13912). During the
      fermentation of Nocardioides luteus, the growth of cells reaches a maximum growth
      at 28 h. C10-deacetylase enzyme activity starts at 26 h and peaks at 38 h of the
      fermentation. The cells are recovered by centrifugation. The C10-deacetylase
      enzyme was purified from the Nocardioides luteus cells. The enzyme was purified
      190-fold to near homogeneity. The purified enzyme appeared as a single band on
      12.5% SDS-PAGE analysis with a molecular weight of 40,000 daltons. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623521
TI  - Fermentation and recovery of glutamic acid from palm waste hydrolysate by Ion
      exchange resin column.
AB  - Glutamic acid produced from palm waste hydrolysate by fermentation with
      Brevibacterium lactofermentum ATCC 13869 is produced with a remarkably high yield
      compared with that produced from pure glucose as a carbon source. The produce
      yield is 70 g/L with glucose, wherease, when palm waste hydrolysate is the
      fermentation medium in the same bioreactor under same conditions, it is 88 g/L.
      The higher yield may be attributed to the fact that this organism has the ability
      to convert sugars other than only glucose present in the hydrolysate. Bioreactor
      conditions most conducive for maximum production are pH 7.5, temperature of 30
      degrees rmentation period of 48 h, inoculum size 6%, substrate concentration of
      10 g per 100 mL, yeast extract 0.5 g per 100 mL as a suitable N source, and
      biotin at a concentration of 10 pg/L. Palm waste hydrolysate used in this study
      was prepared by enzymic saccharification of treated palm press fiber under
      conditions that yielded a maximum of 30 g/L total reducing sugars. Glutamic acid
      from fermentation broth was recovered by using a chromatographic column (5cm x 60
      cm) packed with a strong ion-exchange resin. The filtered broth containing
      glutamic acid and other inorganic ions was fed to the fully charged column. The
      broth was continuously recycled at a flow rate of 50 mL/min (retention time of 55
      min) until glutamic acid was fully adsorbed on the column leaving other ions in
      the effluent. Recovery was done by eluting with urea and sodium hydroxide for
      total displacement of glutamic acid from the resin. The eluent containing 88 g/L
      of glutamic acid was concentrated by evaporation to obtain solid crystals of the
      product. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623523
TI  - A time for change.

PMID- 18623524
TI  - Ion exchange of amino acids at a natural organic ion exchanger: Thermodynamics
      and energetics.
AB  - The thermodynamics and energetics of the ion exchange of four amino acids at a
      cellulosic ion exchanger have been studied. Experimental work included
      determination of ion exchange isotherms and the use of high-sensitivity titration
      microcalorimetry. A rigorous thermodynamic analysis of the data was developed
      allowing calculation of the standard free energy, the standard enthalpy, and
      standard entropy of exchange, and also the differential free energy, incremental
      enthalpy, and incremental entropy of exchange. The results show that the relative
      contributions of the enthalpy and entropy to the overall free energy differ
      markedly for the chosen amino acids. The reasons for these differences are
      analyzed and discussed. A knowledge of these fundamental thermodynamic properties
      indicates the solution conditions likely to give enhanced affinity of the ion
      exchanger for selected amino acids. The experimental techniques and analysis
      procedures developed are generally applicable to ion exchange separations of
      biomolecules. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623525
TI  - Structured modeling and state estimation in a fermentation process: Lipase
      production by Candida rugosa.
AB  - A simple structured mathematical model coupled with a methodology of state and
      parameter estimation is developed for lipase production by Candida rugosa in
      batch fermentation. The model describes the system according to the following
      qualitative observations and hypothesis: Lipase production is induced by
      extracellular oleic acid present in the medium. The acid is transported into the
      cell where it is consumed, transformed, and stored. Lipase is excreted to the
      medium where it is distributed between the available oil-water interphase and
      aqueous phase. Cell growth is modulated by the intracellular substrate
      concentration. Model parameters have been determined and the whole model
      validated against experiments not used in their determination. The estimation
      problem consists in the estimation of three state variables (biomass, intra- and
      extracellular substrate) and two kinetic parameters by using only the on-line
      measurement provided by exhaust gas analysis. The presented estimation strategy
      divides the complex problem into three subproblems that can be solved by stable
      algorithms. The estimation of biomass (X) and the specific growth rate (mu), is
      achieved by a recursive prediction error algorithm using the on-line measurement
      of the carbon dioxide evolution rate. mu is then used to perform an estimation of
      intracellular substrate and the other kinetic parameter related to substrate
      transport (A) by an adaptive observer. Extracellular substrate is then evaluated
      by means of the estimated values of intracellular substrate and biomass through
      the material balance of the reactor. Simulation and experimental tests showed
      good performance of the developed estimator, which appears suitable to be used
      for process control and monitoring. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623526
TI  - Polyphenoloxidases immobilized in organic gels: Properties and applications in
      the detoxification of aromatic compounds.
AB  - Gelatine gels originate from water in oil microemulsions in which the ternary
      system consists of isooctane/ sulfosuccinic acid bis [2-ethyl hexyl] ester/water;
      the solubilization of gelatin in the water pool of these microemulsions
      transforms them into viscous gels in which it is possible to cosolubilize various
      reactive molecules. These gels were used to immobilize two phenoloxidases, a
      laccase from Trametes versicolor and a tyrosinase from mushroom. The best balance
      between gel retention and catalytic activity was reached at a gelatine
      concentration of 2.5% (w/v) in the case of tyrosinase, while laccase
      immobilization was independent of gelatine concentration. Both enzymes kept the
      same optimum pH as the corresponding soluble controls, while a partial loss of
      activity was observed when they were immobilized. Immobilized enzymes showed an
      increased stability when incubated for several days at 4 degrees C with a very
      low release from the gels in the incubation solutions. The immobilization of
      tyrosinase and of laccase enhanced stability to thermal inactivation.
      Furthermore, gel-entrapped tyrosinase was almost completely preserved from
      proteolysis: more than 80% of the activity was maintained, while only 25% of the
      soluble control activity was detected after the same proteolytic treatments. A
      column packed with gel-immobilized tyrosinase was used to demonstrate that
      enzymes immobilized with this technique may be reused several times in the same
      reaction without loosing their efficiency. Finally, gel-entrapped tyrosinase and
      laccase were capable of removing naturally occurring and xeno-biotic aromatic
      compounds from aqueous suspensions with different degrees of efficiency. (c) 1995
      John Wiley & Sons, Inc.

PMID- 18623527
TI  - Bioleaching of pyrite by acidophilic thermophile Acidianus brierleyi.
AB  - The kinetics of bioleaching of pyrite (FeS(2)) by the acidophilic thermophilic
      bacterium Acidianus brierleyi was studied in a well-mixed batch reactor.
      Experiments were done at 65 degrees C and pH 1.5 on adsorption of A. brierleyi
      onto pyrite particles, liquid-phase oxidation of ferrous iron by A. brierleyi,
      and microbial leaching of pyrite. The adsorption of A. brierleyi was a fast
      process; equilibrium was attained within the first 30 min of exposure to pyrite.
      The adsorption equilibrium data were well correlated with the Langmuir isotherm.
      The oxidation of ferrous iron was markedly accelerated in the presence of A.
      brierleyi, and the growth yield on ferrous iron was determined. The bioleaching
      of pyrite by A. brierleyi was found to take place with a direct attack by
      adsorbed cells on the surface of pyrite, the chemical leaching of pyrite by
      ferric iron being insignificant. Rate data collected under a wide variety of
      operating variables were analyzed to determine kinetic and stoichiometric
      parameters for the microbial pyrite leaching. The specific growth rate on pyrite
      for A. brierleyi was about four times that for the mesophilic bacterium,
      Thiobacillus ferrooxidans, whereas the growth yields on pyrite for the two
      microbes were approximately equal to one another in magnitude. A comparison of A.
      brierleyi with T. ferrooxidans for pyrite leachability demonstrated the
      thermophile to be much more effective. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623528
TI  - Fatty acid esterification using nylon-immobilized lipase.
AB  - The esterification of a long-chain fatty acid was conducted using a nylon
      immobilized lipase from Candida cylindracea in a nearly anhydrous, nonpolar
      organic medium, hexane. Butyl laurate was produced from lauric acid and n-butanol
      at a maximum initial reaction rate of 37 mmol/h. g immobilized enzyme when the
      substrates were present in equimolar amounts at an initial concentration of 0.5
      mol/L. Lower rates were obtained using nonstoichiometric amounts of the
      substrates. The rate of reaction increased with temperature, reaching a maximum
      between 35 and 45 degrees C and decreasing sharply at higher temperatures. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623529
TI  - Modeling simultaneous hexavalent chromium reduction and phenol degradation by a
      defined coculture of bacteria.
AB  - Based on the kinetics of Cr(VI) reduction by Escherichia coli ATCC 33456 and
      phenol degradation by Pseudomonas putida DMP-1, a mathematical model is developed
      to describe simultaneous Cr(VI) reduction and phenol degradation in the coculture
      of the two species. The developed model incorporates the toxicity effects of
      Cr(VI) and phenol on phenol degradation and Cr(VI) reduction in the coculture.
      The model illustrates the inhibitory effects of phenol on Cr(VI) reduction and
      Cr(VI) toxicity toward phenol degradation. The model also reveals the recoveries
      of the activities of the repressed bacterial cells with continuous Cr(VI)
      reduction and phenol degradation in the coculture. The model is capable of
      predicting simultaneous Cr(VI) reduction and phenol degradation within a broad
      range of Cr(VI) and phenol concentrations and under an appropriate composition of
      populations. However, the model simulates lower concentrations of phenol than
      experimental observations once Cr(VI) is reduced to a low level (<7 mg/L). The
      model simulation for Cr(VI) also deviates from experimental data when P. putida
      is outnumbered by E. coli by a ratio of 1:5. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623530
TI  - Thermophilic biodegradation of BTEX by two Thermus Species.
AB  - Two thermophilic bacteria, Thermus aquaticus ATCC 25104 and Thermus species ATCC
      27978, were investigated for their abilities to degrade BTEX (benzene, toluene,
      ethylbenzene, and xylenes). Thermus aquaticus and the Thermus sp. were grown in a
      nominal medium at 70 degrees C and 60 degrees C, respectively, and resting cell
      suspensions were used to study BTEX biodegradation at the same corresponding
      temperatures. The degradation of BTEX by these cell suspensions was measured in
      sealed serum bottles against controls that also displayed significant abiotic
      removals of BTEX under such high-temperature conditions. For T. aquaticus at a
      suspension density of only 1.3 x 10(7) cells/mL and an aqueous total BTEX
      concentration of 2.04 mg/L (0.022 mM), benzene, toluene, ethylbenzene, m-xylene,
      and an unresolved mixture of o-and p-xylenes were biodegraded by 10, 12, 18, 20,
      and 20%, respectively, after 45 days of incubation at 70 degrees C. For the
      Thermus sp. at a suspension density of 1.1 x 10(7) cells/mL and an aqueous total
      BTEX concentration of 6.98 mg/L (0.079 mM), benzene, toluene, ethylbenzene, m
      xylene, and the unresolved mixture of o-and p-xylenes were biodegraded by 40, 35,
      32, 33, and 33%, respectively, after 45 days of incubation at 60 degrees C.
      Raising the BTEX concentrations lowered the extents of biodegradation. The
      biodegradations of both benzene and toluene were enhanced when T. aquaticus and
      the Thermus sp. were pregrown on catechol and o-cresol, respectively, as carbon
      sources. Use of [U-(14)C]benzene and [ring-(14)C]toluene verified that a small
      fraction of these two compounds was metabolized within 7 days to water-soluble
      products and CO(2) by these nongrowing cell suspensions. Our investigation also
      revealed that the nominal medium can be simplified by eliminating the yeast
      extract and using a higher tryptone concentration (0.2%) without affecting the
      growth and BTEX degrading activities of these cells. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623531
TI  - Biodegradation of nitrobenzene through a hybrid pathway in Pseudomonas putida.
AB  - The biodegradation of nitrobenzene was attempted by using Pseudomonas putida TB
      103 which possesses the hybrid pathway combining the tod and the tol pathways.
      Analysis of the metabolic flux of nitrobenzene through the hybrid pathway
      indicated that nitrobenzene was initially oxidized to cis-1,2-dihydroxy-3
      nitrocyclohexa-3,5-diene by toluene dioxygenase in the tod pathway and then
      channeled into the tol pathway, leading to the complete biodegradation of
      nitrobenzene. A crucial metabolic step redirecting the metabolic flux of
      nitrobenzene from the tod to the tol pathway was determined from the genetic and
      biochemical studies on the enzymes involved in the tol pathway. From these
      results, it was found that toluate-cis-glycol dehydrogenase could convert cis-1,2
      dihydroxy-3-nitrocyclohexa-3,5-diene to catechol in the presence of NAD(+) with
      liberation of nitrite and the reduced form of NAD(+) (NADH) into the medium. (c)
      1995 John Wiley & Sons, Inc.

PMID- 18623532
TI  - Adaptive on-line model for aerobic Saccharomyces cerevisiae fermentation.
AB  - In order to study and control fermentation processes, indirect on-tine
      measurements and mathematical models can be used. In this article we present a
      mathematical on-line model for fermentation processes. The model is based on atom
      and partial mass balances as well as on equations describing the acid-base
      system. The model is brought into an adaptive form by including transport
      equations for mass transfer and unstructured expressions for the fermentation
      kinetics. The state of the process, i.e., the concentrations of biomass,
      substrate, and products, can be estimated on-line using the balance part of the
      model completed with measurement equations for the input and output flows of the
      process. Adaptivity is realized by means of on-line estimation of parameters in
      the transport and kinetic expressions using recursive regression analysis. These
      expressions can thus be used in the model as valid equations enabling prediction
      of the process. This makes model-based automation of the process and testing of
      the validity of the measurement variables possible. The model and the on-line
      principles are applied to a 3.5-L laboratory tormentor in which Saccharomyces
      cerevisiae is cultivated. The experimental results show that the model-based
      estimation of the state and the predictions of the process correlate closely with
      high-performance liquid chromatography (HPLC) analyses. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623533
TI  - N-glycans of recombinant human interferon-gamma change during batch culture of
      chinese hamster ovary cells.
AB  - A recombinant Chinese hamster ovary (CHO) cell line making human interfron-gamma
      (IFN-gamma) was grown in 12-L stirred tank fermentors in three batch
      fermentations under conditions of constant temperature, pH, and dissolved oxygen
      tension. In addition to cell growth, metabolite, and productivity data, a
      detailed analysis of the carbohydrate structures attached to each glycosylation
      site of IFN-gamma was achieved using matrix-assisted laser desorption mass
      spectrometry (MALDI-MS) in combination with exoglycosidase array sequencing.
      Complex biantennary oligosaccharides (particularly Gal(2)GlcNAc(4)Man(3) which
      was core alephl-6 fucosylated at Asn(25) but not at Asng(97)) were most prevalent
      at both glycosylation sites. However, considerable microheterogeneity arising
      from the presence of triantennary and truncated glycan structures was also
      observed. The proportion of the dominant core glycan structure
      (Gal(2)GlcNAc(4)Man(3) +/- Fuc(1)) decreased by 15-26% during batch culture, with
      increases in the proportion of oligomannose and truncated glycans over the same
      time period. Prolonged culture resulting from an extended lag phase led to
      further accumulation of oligomannose and truncated structures, reaching up to 52%
      of total glycans attached to Asng(97) by 240 h of culture. The implications of
      these glycosylation changes for optimizing the time for harvesting cell cultures,
      and for the clearance of recombinant therapeutic products in vivo are discussed.
      (c) 1995 John Wiley & Sons, Inc.

PMID- 18623534
TI  - Thermodynamic approach to explain cell adhesion to air-medium interfaces.
AB  - Cell damage has been observed in suspension cell cultures with air sparging,
      especially in the absence of any protective additives. This damage is associated
      with cells adhering to bubbles, and it has been shown that if this adhesion is
      prevented, cell damage is prevented. This article presents a thermodynamic
      approach for predicting cell adhesion at the air-medium interface. With this
      relationship it can be shown that cell-gas adhesion can be prevented by lowering
      the surface tension of the liquid growth medium through the addition of surface
      active protective additives. The thermodynamic relationship describes the change
      in free energy as a function of the interfacial tensions between the (i) gas and
      liquid phases, (ii) gas and cell phases, and (iii) liquid and cell phases.
      Experimental data, along with theoretical and empirical equations, are used to
      quantify the changes in free energy that predict the process of cell-gas
      adhesion. The thermodynamic model is nonspecific in nature and, consequently,
      results are equally valid for all types of cells. (c) 1995 John Wiley & Sons,
      Inc.

PMID- 18623535
TI  - Kinetics of chlorinated ethylene dehalogenation under methanogenic conditions.
AB  - Kinetics were determined for methanogenic activity and chlorinated ethylene
      dehalogenation by a methanol-enriched, anaerobic sediment consortium. The culture
      reductively dechlorinated perchloroethylene (PCE) to trichloroethylene (TCE), 1,1
      dichloroethylene (1,1-DCE), vinylchloride (VC), and ethylene and ethane. The
      absence : of methanol or the addition of 2-bromoethanesulfonic. acid in the
      presence of methanol suppressed both methanogenic activity and dechlorination. In
      contrast, acetate production continued in the presence of 2-bromoethanesulfonic
      acid. These results suggest that dechlorination was strongly linked to methane
      formation and not to acetate production. A kinetic model, developed to describe
      both methanogenesis and dechlorination, successfully predicted experimentally
      measured concentrations of biomass, methane, substrate, and chlorinated
      ethylenes. The average maximum specific dehalogenation rates for PCE, TCE, 1,1
      DCE, and VC were 0.9 +/- 0.6, 0.4 +/- 0.1, 12 +/- 0.1, and 2.5 +/- 1.7 mumol
      contaminant/ g. DW/day, respectively. This pattern for dechlorination rates is
      distinctly different than that reported for transition metal cofactors, where
      rates drop by approximately one order of magnitude as each successive chlorine is
      removed. The experimental results and kinetic analysis suggest that it will be
      impractical to targeting methanol consuming methanogenic organisms for in situ
      ground-water restoration. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623536
TI  - Simultaneous light emission from cloned Vibrio fischeri lux genes and expression
      of LamB or LamB-protein A fusion proteins in Escherichia coli depends on using a
      single chimeric operon.
AB  - Fusion proteins between LamB and immunoglobulin G binding domains of the
      Staphylococcus aureus protein A (SPA) have previously been shown to be located in
      the outer membrane and to convey immunoglobulin binding activity to intact
      Escherichia coli cells. However, the induced synthesis (tac promoter dependent)
      of these proteins severely impaired light production from the Vibrio fischeri lux
      operon present on a compatible plasmid and transcribed from its own control
      elements. Coordinate inducible expression of both phenomena, light emission and
      synthesis of LamB or LamB-SPA fusions, could be achieved by construction of
      artificial operons, joining all but luxl of the rightward lux operon to the 3'
      end of the LamB-spa expression cassettes, under transcriptional control of the
      tac promoter. Biotechnological applications are discussed. (c) 1995 John Wiley &
      Sons, Inc.

PMID- 18623537
TI  - Enhancement of antibody production by growth factor addition in perfusion and
      hollow-fiber culture systems.
AB  - The effects of the high-molecular-weight growth factors, transferrin and bovine
      serum albumin (BSA), on antibody production were analyzed quantitatively in
      continuous hollow-fiber cultivation over a period of 60 days. Transferrin
      enhanced cell growth but had no significant effect on the specific antibody
      production rate, whereas BSA significantly enhanced antibody production. The
      antibody production rate was increased 4- and 14-fold respectively by feeding BSA
      at 2 and 5 g L(-1) into the EC side of the system (the side connected to the cell
      containing outer part of the hollow-fiber unit) compared with the production
      achieved without BSA. Addition of 5 g L(1) BSA into the IC side of the system
      (the side connected to the inner part of the hollow-fiber unit) resulted in a 2.5
      fold increase in the antibody production rate. The effect of BSA was also
      analyzed using the perfusion culture system with a separation unit. When fresh
      medium containing either 2 or 5 g L(-1) BSA was fed into the reactor, both the
      specific growth rate and specific death rate increased, while the specific
      antibody production rate was increased 2- and 25-fold, respectively, by feeding
      BSA at these two concentrations compared with no addition. Comparing the two
      systems, the increase in the antibody production rate achieved with the hollow
      fiber system was threefold greater than that in the perfusion culture system with
      the same concentration of BSA feeding. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623538
TI  - A metabolic network stoichiometry analysis of microbial growth and product
      formation.
AB  - Using available biochemical information, metabolic networks have been constructed
      to describe the biochemistry of growth of Saccharomyces cerevisiae and Candida
      utilis on a wide variety of carbon substrates. All networks contained only two
      fitted parameters, the P/O ratio and a maintenance coefficient. It is shown that
      with a growth-associated maintenance coefficient, K, of 1.37 mol ATP/ C-mol
      protein for both yeasts and P/O ratios of 1.20 and 1.53 for S. cerevisiae and C.
      utilis, respectively, measured biomass yields could be described accurately. A
      metabolic flux analysis of aerobic growth of S. cerevisiae on glucose/ethanol
      mixtures predicted five different metabolic flux regimes upon transition from
      100% glucose to 100% ethanol. The metabolic network constructed for growth of S.
      cerevisiae on glucose was applied to perform a theoretical exercise on the
      overproduction of amino acids. It is shown that theoretical operational product
      yield values can be substantially lower than calculated maximum product yields. A
      practical case of lysine production was analyzed with respect to theoretical
      bottlenecks limiting product formation. Predictions of network-derived
      irreversibility limits for Y(sp) (mu) functions were compared with literature
      data. The comparisons show that in real systems such irreversibility constraints
      may be of relevance. It is concluded that analysis of metabolic network
      stoichiometry is a useful tool to detect metabolic limits and to guide process
      intensification studies. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623539
TI  - Enhancement of monoclonal antibody production by immobilized hybridoma cell
      culture with hyperosmolar medium.
AB  - To determine the effect of hyperosmotic stress on the monoclonal antibody (MAb)
      production by calcium-alginate-immobilized S3H5/gamma2bA2 hybridoma cells, the
      osmolalities of medium in the MAb production stage were varied through the
      addition of NaCI. The specific MAb productivity (q(MAb)) of immobilized cells
      exposed to abrupt hyperosmotic stress (398 mOsm/kg) was increased by 55% when
      compared with that of immobilized cells in the control culture (286 mOsm/kg).
      Furthermore, this enhancement of q(MAb) was not transient. Abrupt increase in
      osmolality, however, inhibited cell growth, resulting in no increase in
      volumetric MAb productivity (r(MAb)). On the other hand, gradual increase in
      osmolality allowed further cell growth while maintaining the enhanced q(MAb)
      immobilized cells. The q(MAb) immobilized cells at 395 mOsm/kg was 0.661 +/-
      0.019 mug/10(6) cells/h, which is almost identical to that of immobilized cells
      exposed to abrupt osmotic stress. Accordingly, the r(MAb) was increased by ca.
      40% when compared with that in the control immobilized cell culture. This
      enhancement in i(MAb) of immobilized S3H5/gamma2bA2 hybridoma cells by applying
      gradual osmotic stress suggests the potential of using hyperosmolar medium in
      other perfusion culture systems for improved MAb production. (c) 1995 John Wiley
      & Sons, Inc.

PMID- 18623540
TI  - Characterization of free and alginate-polylysine-alginate microencapsulated
      Erwinia herbicola for the conversion of ammonia, pyruvate, and phenol into L
      tyrosine.
AB  - The whole cell tyrosine phenol-lyase (TPL, E.C. 4.1.99.2) activity of Erwinia
      herbicola (ATCC 21434) was microen-capsulated. We studied the use of this for the
      conversion of ammonia and pyruvate along with phenol or catechol, respectively,
      into L-tyrosine or dihydroxyphenyl-L-alanine (L-dopa). The reactions are relevant
      to the development of new methods for the production of L-tyrosine and L-dopa.
      The growth of E. herbicola at temperatures from 22 degrees C to 32 degrees C is
      stable, since at these temperatures the cells grow up to the stationary phase and
      remain there for at least 10 h. At 37 degrees C the cells grow rapidly, but they
      also enter the death phase rapidly. There is only limited growth of E. herbicola
      at 42 degrees C. Whole cells of E. herbicola were encapsulated within alginate
      polylysine-alginate microcapsules (916 +/- 100 mum, mean +/- std. dev.). The TPL
      activity of the cells catalyzed the production of L-tyrosine or dihydroxyphenyl-L
      alanine (L-dopa) from ammonia, pyruvate, and phenol or catechol, respectively. In
      the production of tyrosine, an integrated equation based on an ordered ter-uni
      rapid equilibrium mechanism can be used to find the kinetic parameters of TPL. In
      an adequately stirred system, the apparent values of-the kinetic parameters of
      whole cell TPL are equal whether the cells are free or encapsulated. The apparent
      K(M) of tyrosine varies with the amount of whole cells in the system, ranging
      from 0.2 to 0.3 mM. The apparent K(M) for phenol is 0.5 mM. The apparent K(M)
      values for pyruvate and ammonia are an order of magnitude greater for whole cells
      than they are for the cell free enzyme. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623541
TI  - The kinetics of RCC1 inclusion body formation in Escherichia Coli.
AB  - The Regulator of Chromosome Condensation protein (RCC1) is located in both the
      soluble and inclusion body (IB) fractions of the whole cell lysate when expressed
      in Escherichia coli BL21 (pLysS) at temperatures below 30 degrees C. When
      bacterial growth was carried out at 20 degrees C, the majority of the RCC1
      remained soluble up to 5.5 h postinduction, When the temperature was raised to 25
      degrees C, RCC1 IB was dominant by 1.5 h postinduction. The shift in RCC1 IB
      formation with temperature suggests that in addition to increased translation
      rates, folding and aggregation processes may contribute to RCC1 IB formation at
      higher temperatures. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623542
TI  - Effects of fungal pretreatment and steam explosion pretreatment on enzymatic
      saccharification of plant biomass.
AB  - The effects of consecutive treatments by a lignin-degrading fungus Phanerochaete
      chrysosporium and by steam explosion for the enzymatic saccharification of plant
      biomass were studied experimentally, and the optimal operational conditions for
      obtaining the maximum saccharification were evaluated. Beech wood-meal was
      treated by the fungus for 98 days and then by high steam temperatures of 170-230
      degrees C with steaming times of 0-10 min. The treatment of the wood-meal by
      fungus prior to steam explosion enhanced the saccharification of wood-meal. The
      treated wood-meal was separated into holo-cellulose, water soluble material,
      methanol soluble lignin, and Klason lignin. The saccharification decreased
      linearly with the increase in the amount of Klason lignin. It was estimated by
      the equation for the saccharification of exploded wood-meal expressed as a
      function of steam temperature and steaming time that the maximum saccharification
      of wood-meal was obtained by consecutive treatments such as fungal treatment for
      28 days and then steam explosion at a steam temperature of 215 degrees C and a
      steaming time of 6.5 min. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623543
TI  - Comprehensive modeling of methanogenic biofilms in fluidized bed systems: Mass
      transfer limitations and multisubstrate aspects.
AB  - A cognitive model for anaerobic digestion in fluidized bed reactors is developed.
      The general pathway of the process is divided into five main reactions performed
      by different bacterial groups. Molecular diffusion of each substrate involved in
      the reaction scheme is described. Effectiveness factor calculations are performed
      in steady state for each bacterial group taken into account in the process. The
      case of a single substrate removal is discussed, and optimal biofilm sizes are
      found. Sequential substrate removal is investigated, and different kinetic
      regimes are characterized. The influence of biofilm size and primary substrate
      removal is discussed in the case of standard concentrations in the liquid phase.
      This study shows that, according to the theoretical model the limiting step of
      the process may be different and depends in a large way on mass transfer effects.
      Finally, importance of biofilm size is compared for acidogenic and methano-genic
      steps: each reaction is found to be optimized for different biofilm thicknesses.
      This result may be of interest for design purposes and further dynamic modeling.
      Concluding remarks concerning the validation of the model are made, and a
      comparison to experimental data from the literature is presented. (c) 1995 John
      Wiley & Sons, Inc.

PMID- 18623544
TI  - Measurement of local mass transfer coefficient in biofilms.
AB  - Local mass transfer rates for an electrochemically formed microsink in an aerobic
      biofilm was measured by a mobile microelectrode using limiting current technique.
      Mass transfer coefficients varied both horizontally and vertically in the
      biofilm. The results implied the existence of an irregular biofilm structure
      consisting of microbial cell clusters surrounded by tortuous water channels. An
      unexpected increase of the local mass transfer coefficient just above the biofilm
      surface suggested the existence, of local flow instability in this region. As
      expected, the influence of bulk flow velocity on the local mass transfer rate
      decreased with increasing depth into the biofilm. Mass transfer coefficients
      fluctuated significantly inside microbial cell clusters, suggesting the existence
      of internal channels through which liquid could flow. A new conceptual model of
      biofilm microbial cluster structure is proposed to account for such biofilm
      microstructure irregularities. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623545
TI  - Purification of industrial alphaamylase by reversed micellar extraction.
AB  - The purification of industrial alpha-amylase by liquid-liquid extraction with
      Aliquat 336 reversed micellar solution as the extractant was studied. Seven kinds
      of Aliquat 336 reversed micellar solution, formed by using seven kinds of
      straight chain alkyl alcohols as cosolvent, have been utilized to extract
      industrial a-amylase. It was found that these seven kinds of reversed micellar
      solution can all achieve a high protein transfer efficiency in the forward
      extraction process. After a full forward and backward extraction cycle, however,
      only the reversed micelles with n-butanol as the cosolvent was found to be able
      to maintain the activity of alpha-amylase in the stripping solution. By using the
      reversed micelles of Aliquat 336/isooctane/1% (v/v) n-butanol to perform a full
      extraction cycle, it was found that 85% of the total activity of alpha-amylase in
      the industrial a-amylase could be recovered at the end of an extraction cycle and
      the specific activity of alpha-amylase could be concentrated about 1.5-fold;
      meanwhile, most of the neutral protease in the industrial a-amylase could be
      removed. The separation factor of alpha-amylase to neutral protease at the end of
      an extraction cycle can reach about 10. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623547
TI  - Bacterial polyhydroxyalkanoates.
AB  - Polyhydroxyalkanoates (PHAs) are polyesters of hydroxyalkanoates (HAs)
      synthesized by numerous bacteria as intracellular carbon and energy storage
      compounds and accumulated as granules in the cytoplasm of cells. More than 80 HAs
      have been detected as constituents of PHAs, which allows these thermoplastic
      materials to have various mechanical properties resembling hard crystalline
      polymer or elastic rubber depending on the incorporated monomer units. Even
      though PHAs have been recognized as good candidates for biodegradable plastics,
      their high price compared with conventional plastics has limited their use in a
      wide range of applications. A number of bacteria including Alcaligenes eutrophus,
      Alcaligenes latus, Azotobacter vinelandii, methylotrophs, pseudomonads, and
      recombinant Escherichia coli have been employed for the production of PHAs, and
      the productivity of greater than 2 g PHA/L/h has been achieved. Recent advances
      in understanding metabolism, molecular biology, and genetics of the PHA
      synthesizing bacteria and cloning of more than 20 different PHA biosynthesis
      genes allowed construction of various recombinant strains that were able to
      synthesize polyesters having different monomer units and/or to accumulate much
      more polymers. Also, genetically engineered plants harboring the bacterial PHA
      biosynthesis genes are being developed for the economical production of PHAs.
      Improvements in fermentation/separation technology and the development of
      bacterial strains or plants that more efficiently synthesize PHAs will bring the
      costs down to make PHAs competitive with the conventional plastics.

PMID- 18623548
TI  - A fluid dynamic study using a simulated viscous, shear thinning broth of the
      retrofitting of large agitated bioreactors.
AB  - Studies were conducted(1) in 19-m(3) fermentors (14-m(3) working volume) using
      four Rushton turbines, four Prochem Maxflo Ts, and three Lightnin' A315s and the
      results in water have been reported earlier. Here, a 1.7 wt/vol% Xanthan solution
      has been used as the working fluid, simulating viscous broths to give Reynolds
      numbers (Re) between 1800 and 4500. As predicted from small-scale studies, the
      power numbers at these values of Re were similar to those in water. The K factor
      (the ratio of power draw under aerated conditions compared to non-aerated) was
      the same as in water at the higher values of Re, but at the lower values it fell
      more rapidly with increasing aeration rate and to a lower value than in water. At
      all times, K was higher than with Rushton turbines. Vibration characteristics
      were also measured. Under aerated conditions, the fermentors vibrated with an
      amplitude 75% to 100% less than in water due to viscous damping. With increasing
      air flow, the amplitude increased steadily due to the presence of very large and
      rapidly rising bubbles in such fluids to give values 2.5 to 3 times those in
      water. Nevertheless, these mechanical problems can be overcome, allowing such
      agitators to be used successfully in high viscosity mycelial fermentations.

PMID- 18623549
TI  - A new continuous biofilm bioreactor for immobilized oil-degrading filamentous
      fungi.
AB  - A new type of horizontal biofilm bioreactor for continuous bioconversion of
      emulsified oily substrate by immobilized growing biofilm of filamentous fungi was
      designed, constructed, and feasibility tested. The new reactor design provides
      "self"-immobilization of homogenized mycelium leading to even biofilm
      development. This was accomplished by using stainless steel screens of optimal
      mesh, mounted in parallel and stretching outward from a main rotating axis of a
      biological rotating contractor. Each screen was equipped with a pair of stainless
      steel blades mounted on supports allowing for continuous biofilm "shaving" beyond
      a predetermined thickness, thus retaining freshly growing active biofilm surface.
      The feasibility of the new bioreactor was demonstrated by decalactone production
      from emulsified castor oil by immobilized filamentous fungi (Tyromyces
      sambuceus). The combination of oriented metal screens and moving blades was found
      to be highly effective for a model system in maintaining stable substrate
      emulsion in the reactor in either batchwise or continuous processing, as well as
      maintaining biofilm thickness with continuous removal of excess growing hyphae.

PMID- 18623550
TI  - New approaches for verification of kinetic parameters of immobilized concanavalin
      A: invertase preparations investigated by flow microcalorimetry.
AB  - In our preceding article, we demonstrated a procedure based upon enzymic flow
      microcalorimetry using an enzyme thermistor (ET) to characterize the microkinetic
      properties of an immobilized enzyme (IME) and its further application in the
      screening of IMEs. To consider the ET method (single ET unit, ET system 1) as
      standard, it was necessary to show that the estimated relative kinetic parameter
      (DeltaT(max)) calorimetrically corresponds with the absolute value for the
      reaction rate within the whole measurement range. This article presents three
      experimental verification procedures. Two procedures are based on adaptation of
      the flow-through ET column to a mini-differential-reactor (DR) system with
      substrate recirculation and post-ET-column methods for determination of the
      concentration change of the product (spectrophotometrically in ET system 2) or
      the substrate (calorimetrically in ET system 3) with the IME-catalyzed enzymic
      hydrolysis. The third procedure is an independently operating DR system which
      spectrophotometrically estimates the concentration change of the product. The
      results obtained exhibited good correlation (r = 0.921) between the relative
      kinetic parameter DeltaT(max), as determined calorimetrically by ET system 1, and
      the absolute value for the reaction rate (r(max)) as determined by ET systems 2
      and 3. These data proved that, within the whole range of experimental conditions
      applied in this study, the parameter DeltaT(max) instead of the true reaction
      rate could be employed for the IME screening. Moreover, the generality of the
      detection principle and the standardized configuration of the ET favor ET systems
      2 and 3 for normal screening of IMEs and as miniaturized DR systems allowing dual
      measurements of kinetic parameters.

PMID- 18623551
TI  - Enhanced alpha-amylase production in recombinant Bacillus brevis by fed-batch
      culture with amino acid control.
AB  - Fed-batch culture with controlled L-amino acid composition was performed to
      improve production of a recombinant gene product in Bacillus brevis. The maximum
      recombinant protein (alpha-amylase) level and specific activity increased from
      5.14 kU/mL and 0.77 kU/mg dry cell in conventional fed-batch culture to 12.01
      kU/mL and 2.64 kU/mg dry cell, respectively, when L-amino acid concentration was
      controlled at 5 mM using an asparagine (Asn)- and isoleucine (Ile)-enriched
      nitrogen source. The L-amino acid concentration in the culture was monitored by
      an automatic biotech analyzer and controlled at 2-20 mM using a mixture of
      polypeptone and yeast extract. Although L-amino acid concentrations were
      controlled at low levels, the alpha-amylase activity increased only 1.3 times
      compared to an uncontrolled batch culture; accumulation of ammonium ion was not
      reduced. When L-amino acid was controlled at the high level, more cell mass and
      less recombinant gene product were produced than in those with low control level.
      To overcome ammonium ion inhibition, the specific amino acids Asn and Ile were
      substituted to improve the production of gene product. Addition of these amino
      acids to a flask culture led to an improvement in the enzyme production level and
      specific activity to 2.9 and 5.1 times, respectively, as high as that without
      them. Both the control of amino acids at low concentrations and the enrichment of
      Asn and Ile were effective for the improvement of recombinant protein production
      from recombinant B. brevis cells.

PMID- 18623552
TI  - G418 Selection and stability of cloned genes integrated at chromosomal delta
      sequences of Saccharomyces cerevisiae.
AB  - The chromosomal delta sequences of the yeast Saccharomyces cerevisiae were
      employed as recombination sites to integrate the bacterial neo(r) gene and the
      yeast SUC2 gene into the yeast genome. A dominate selection method employing the
      aminoglycoside antibiotic G418 was used. Transformation efficiencies and growth
      behaviors of the transformants were studied. Transformants were obtained with
      more than 40 integrations; the majority of insertions were tandem with a maximum
      of three different insertion sites utilized at one time. After 70-100 generations
      of growth in nonselective medium, the high copy number SUC2-neo(r) integrants
      were found to be unstable; only minor instability was observed for the neo(r) and
      low copy number SUC2-neo(r) integrants.

PMID- 18623553
TI  - Production of L-phenylacetylcarbinol (L-PAC) from benzaldehyde using partially
      purified pyruvate decarboxylase (PDC).
AB  - Biotransformation of benzaldehyde to L-phenylacetylcarbinol (L-PAC) as a key
      intermediate for L-ephedrine synthesis has been evaluated using pyruvate
      decarboxylase (PDC) partially purified from Candida utilis. PDC activity was
      enhanced by controlled fermentative metabolism and pulse feeding of glucose prior
      to the enzyme purification. With partially purified PDC, several enzymatic
      reactions occurred simultaneously and gave rise to by-products (acetaldehyde and
      acetoin) as well as L-PAC production. Optimal reaction conditions were determined
      for temperature, pH, addition of ethanol, PDC activity, benzaldehyde, and
      pyruvate:benzaldehyde ratio to maximize L-PAC, and minimize by-products. The
      highest L-PAC concentration of 28.6 g/L (190.6 mM) was achieved at 7 U/mL PDC
      activity and 200 mM benzaldehyde with 2.0 molar ratio of pyruvate to benzaldehyde
      in 40 mM potassium phosphate buffer (pH 7.0) containing 2.0 M ethanol at 4
      degrees C.

PMID- 18623554
TI  - Oxygen effect on lactose catabolism by a Leuconostoc mesenteroides strain:
      modeling of general O2-dependent stoichiometry.
AB  - Lactose metabolism of a Leuconostoc mesenteroides strain was studied in batch
      cultures at a pH of 6.5 and 30 degrees C in 10 L of a modified MRS (De Man,
      Rogosa, Sharp) broth. The end products of this heterolactic bacterium were D
      lactate, acetate, ethanol, and carbon dioxide. To test the effect of oxygen on
      their synthesis, the medium was sparged with different gases: nitrogen, air, and
      pure oxygen. When oxygen was available, oxygen uptake occurred, which caused a
      modification in acetate and ethanol production but not in lactate or carbon
      dioxide production; acetate plus ethanol together were produced in constant
      amounts, which were independent of the level of aeration. The influence of oxygen
      on end-product formation could be summed up by the general equation: lactose + x
      O(2) --> 2 D-lactate + (x + 0.1) acetate + (2 - x) ethanol + 2 CO(2). Maximal
      oxygen uptake (x = 2) was reached under a 120 L/h flow rate of pure oxygen. In
      addition, this equation provided useful information on the possible pathway of
      galactose catabolism by a heterofermentative microorganism.

PMID- 18623555
TI  - Enantioselective hydrolysis of p-nitrostyrene oxide by an epoxide hydrolase
      preparation from Aspergillus niger.
AB  - The epoxide hydrolase activity of Aspergillus niger was synthesized during growth
      of the fungus and was shown to be associated with the soluble cell fraction. An
      enzyme preparation was worked out which could be used in place of the whole
      mycelium as biocatalyst for the hydrolysis of epoxides. The effect of four
      different cosolvents on enzyme activity was investigated. Consequently,
      dimethylsulfoxide (DMSO) was selected for epoxide solubilization. The effect of
      temperature on both reaction rate and enzyme stability was studied in the
      presence of DMSO (0.2 volume ratio). A temperature of 25 degrees C was selected
      for the reaction of bioconversion. With a substrate concentration of 4.5 mM a
      batch reactor showed that the enzyme preparation hydrolyzed para-nitrostyrene
      oxide with very high enantioselectivity. The (S) enantiomer of the epoxide
      remained in the reaction mixture and showed an enantiomeric excess higher than
      99%. The substrate concentration could be increased to 20 mM without affecting
      the enantiomeric excess and degree of conversion. Therefore, the method is
      potentially useful for the preparative resolution of epoxides. Application are in
      the field of chiral synthons which are important building blocks in organic
      synthesis.

PMID- 18623556
TI  - Transient and stationary operating conditions on performance of lactic acid
      bacteria crossflow microfiltration.
AB  - A filtration rig equipped with a tubular alumina membrane was used to study the
      performance of crossflow microfiltration of Lactobacillus helveticus. Experiments
      were performed at constant permeation flux. High cell concentrations and fast
      transient conditions to the stationary J adversely affected permeability.
      Membrane fouling was due to a fast irreversible layer formation and to a
      reversible cell cake. This microbial deposit characteristics were dependent on
      the ratio permeation flux/wall shear stress, J/tau(w). Fouling was faster and
      more severe when J/tau(w) was greater than a critical value of 1.15 L(-1) x h(-1)
      x m(-2) x Pa(-1). The disordered structure of this cell cake seemed to lead to a
      macromolecule deposit between the cells which adversely affected the membrane
      permeability.

PMID- 18623557
TI  - Remarkable activation of enzymes in nonaqueous media by denaturing organic
      cosolvents.
AB  - The rates of transesterification reactions catalyzed by the protease subtilisin
      Carlsberg suspended in various anhydrous solvents at 30 degrees C can be
      increased more than 100-fold by the addition of denaturing organic cosolvents
      (dimethyl sulfoxide or formamide); in water, the same cosolvents exert no enzyme
      activation. At 4 degrees C, the activation effect on the lyophilized protease is
      even higher, reaching 1000-fold. Marked enhancement of enzymatic activity in
      anhydrous solvents by formamide is also observed for two other enzymes, alpha
      chymotrypsin and Rhizomucor miehei lipase, and is manifested in two
      transesterification reactions. In addition to lyophilized subtilisin, crosslinked
      crystals of subtilisin are also amenable to the dramatic activation by the
      denaturing cosolvents. In contrast, subtilisin solubilized in anhydrous media by
      covalent modification with poly(ethylene glycol) exhibits only modest activation.
      These observations are rationalized in terms of a mechanistic hypothesis based on
      an enhanced protein flexibility in anhydrous millieu brought about by the
      denaturing organic cosolvents. The latter exert their lubricating effect largely
      at the interfaces between enzyme molecules in a solid preparation, thus easing
      the flexibility constraints imposed by protein-protein contacts.

PMID- 18623558
TI  - Transport limitation of chlorine disinfection of Pseudomonas aeruginosa entrapped
      in alginate beads.
AB  - An artificial biofilm system consisting of Pseudomonas aeruginosa entrapped in
      alginate and agarose beads was used to demonstrate transport limitation of the
      rate of disinfection of entrapped bacteria by chlorine. Alginate gel beads with
      or without entrapped bacteria consumed chlorine. The specific rate of chlorine
      consumption increased with increasing cell loading in the gel beads and decreased
      with increasing bead radius. The value of an observable modulus comparing the
      rates of reaction and diffusion ranged from less than 0.1 to 8 depending on the
      bead radius and cell density. The observable modulus was largest for large (3-mm
      diameter) beads with high cell loading (1.8 x 10(9) cfu/cm(3)) and smallest for
      small beads (0.5 mm diameter) with no cells added. A chlorine microelectrode was
      used to measure chlorine concentration profiles in agarose beads (3.0 mm
      diameter). Chlorine fully penetrated cell-free agarose beads rapidly; the
      concentration of chlorine at the bead center reached 50% of the bulk
      concentration within approximately 10 min after immersion in chlorine solution.
      When alginate and bacteria were incorporated into an agarose bead, pronounced
      chlorine concentration gradients persisted within the gel bead. Chlorine did
      gradually penetrate the bead, but at a greatly retarded rate; the time to reach
      50% of the bulk concentration at the bead center was approximately 46 h. The
      overall rate of disinfection of entrapped bacteria was strongly dependent on cell
      density and bead radius. Small beads with low initial cell loading (0.5 mm
      diameter, 1.1 x 10(7) cfu/cm(3)) experienced rapid killing; viable cells could
      not be detected (<1.6 x 10(5) cfu/cm(3)) after 15 min of treatment in 2.5 mg/L
      chlorine. In contrast, the number of viable cells in larger beads with a higher
      initial cell density (3.0 mm diameter, 2.2 x 10(9) cfu/cm(3)) decreased only
      about 20% after 6 h of treatment in the same solution. Spatially nonuniform
      killing of bacteria within the beads was demonstrated by measuring the transient
      release of viable cells during dissolution of the beads. Bacteria were killed
      preferentially near the bead surface. Experimental results were consistent with
      transport limitation of the penetration of chlorine into the artificial biofilm
      arising from a reaction-diffusion interaction. The methods reported here provide
      tools for diagnosing the mechanism of biofilm resistance to reactive
      antimicrobial agents in such applications as the treatment of drinking and
      cooling waters.

PMID- 18623559
TI  - Genetic engineering to contain the Vitreoscilla hemoglobin gene enhances
      degradation of benzoic acid by Xanthomonas maltophilia.
AB  - Xanthomonas maltophilia was transformed with the gene encoding Vitreoscilla
      (bacterial) hemoglobin, vgb, and the growth of the engineered strain was compared
      with that of the untransformed strain using benzoic acid as the sole carbon
      source. In general, growth of the engineered strain was greater than that of the
      untransformed strain; this was true for experiments using both overnight cultures
      and log phase cells as inocula, but particularly for the latter. In both cases
      the engineered strain was also more efficient than the untransformed strain in
      converting benzoic acid into biomass.

PMID- 18623560
TI  - A rapid method for determining kinetic parameters of enzymes exhibiting nonlinear
      thermal inactivation behavior.
AB  - A rapid method is developed to analyze the kinetics of thermal inactivation of
      enzymes that exhibit a nonlinear biphasic log(activity)-time relationship.
      Thermal destruction experiments on alcohol dehydrogenase from baker's yeast
      demonstrate the applicability of the method. The method is based on physical
      considerations (as opposed to mathematical curve fitting/regression methods) and
      also serves as a quick check of results obtained using nonlinear regression. It
      is superior to fitting nonlinear enzyme inactivation data by first-order kinetics
      or taking the initial and final slopes of the inactivation data. In fact, the
      method is of general validity and can be applied to any decay process that can be
      represented by a sum of exponentials.

PMID- 18623562
TI  - Determination of the fluxes in the central metabolism of Corynebacterium
      glutamicum by nuclear magnetic resonance spectroscopy combined with metabolite
      balancing.
AB  - To determine the in vivo fluxes of the central metabolism we have developed a
      comprehensive approach exclusively based on the fundamental enzyme reactions
      known to be present, the fate of the carbon atoms of individual reactions, and
      the metabolite balance of the culture. No information on the energy balance is
      required, nor information on enzyme activities, or the directionalities of
      reactions. Our approach combines the power of (1)H-detected (13)C nuclear
      magnetic resonance spectroscopy to follow individual carbons with the simplicity
      of establishing carbon balances of bacterial cultures. We grew a lysine-producing
      strain of Corynebacterium glutamicum to the metabolic and isotopic steady state
      with [1-(13)C]glucose and determined the fractional enrichments in 27 carbon
      atoms of 11 amino acids isolated from the cell. Since precursor metabolites of
      the central metabolism are incorporated in an exactly defined manner in the
      carbon skeleton of amino acids, the fractional enrichments in carbons of
      precursor metabolites (oxaloacetate, glyceraldehyde 3-phosphate, erythrose 4
      phosphate, etc.) became directly accessible. A concise and generally applicable
      mathematical model was established using matrix calculus to express all
      metabolite mass and carbon labeling balances. An appropriate all-purpose software
      for the iterative solution of the equations is supplied. Applying this
      comprehensive methodology to C. glutamicum, all major fluxes within the central
      metabolism were determined. The result is that the flux through the pentose
      phosphate pathway is 66.4% (relative to the glucose input flux of 1.49 mmol/g dry
      weight h), that of entry into the tricarboxylic acid cycle 62.2%, and the
      contribution of the succinylase pathway of lysine synthesis 13.7%. Due to the
      large amount and high quality of measured data in vivo exchange reactions could
      also be quantitated with particularly high exchange rates within the pentose
      phosphate pathway for the ribose 5-phosphate transketolase reaction. Moreover,
      the total net flux of the anaplerotic reactions was quantitated as 38.0%. Most
      importantly, we found that in vivo one component within these anaplerotic
      reactions is a back flux from the carbon 4 units of the tricarboxylic acid cycle
      to the carbon 3 units of glycolysis of 30.6%. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623563
TI  - Production of parvovirus B19 vaccine in insect cells co-infected with double
      baculoviruses.
AB  - Recombinant human parvovirus B19 virus-like particles (VLPs), a candidate
      vaccine, were produced using the insect cell (Sf-9)-baculovirus (AcNPV)
      expression system. The synthesis and assembly of the particles in Sf-9 cells are
      directed by double infections with one recombinant virus (bacVP1) expressing the
      parvovirus minor viral protein VP1 and a second virus (bacVP2) expressing the
      major viral protein VP2. Previous animal studies demonstrated that the
      polypeptide composition of the VLPs strongly affects the elicitation of virus
      neutralizing antibodies. The key factor controlling the production of an
      immunologically potent product in bioreactors was identified to be the
      multiplicity of infection (MOI) of bacVP1 and bacVP2 used for infection. A
      probabilistic model, which correlates well with the experimental results, was
      employed to facilitate the selection of MOIs and to provide a better
      understanding of the baculovirus co-infection process. A novel production process
      based on secondary infections was developed to ensure product consistency and to
      simplify large-scale logistics. The effects of other critical process parameters,
      such as temperature, dissolved oxygen concentration, lactate concentration, cell
      concentration at infection, and harvest time, were also investigated. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18623564
TI  - Effect of Vitreoscilla hemoglobin dosage on microaerobic Escherichia coli carbon
      and energy metabolism.
AB  - The amount of Vitreoscilla hemoglobin (VHb) expression was modulated over a broad
      range with an isopropyl-beta-D-thiogalactopyranoside- (IPTG-) inducible plasmid,
      and the consequences on microaerobic Escherichia coli physiology were examined in
      glucose fed-batch cultivations. The effect of IPTG induction on growth under
      oxygen-limited conditions was most visible during late fed-batch phase where the
      final cell density increased initially linearly with increasing VHb
      concentrations, ultimately saturating at a 2.7-fold increase over the VHb
      negative (Vhb(-)) control. During the same growth phase, the specific excretions
      of fermentation by-products, acetate, ethanol, formate, lactate, and succinate
      from the culture expressing the highest amount of VHb were reduced by 25%, 49%,
      68%, 72%, and 50%, respectively, relative to the VHb(-) control. During the
      exponential growth phase, VHb exerted a positive but smaller control on growth
      rate, growth yield, and respiration. Varying the amount of VHb from 0 to 3.8
      mumol/g dry cell weight (DCW) increased the specific growth rate, the growth
      yield, and the oxygen consumption rate by 33%, 35%, and 60%, respectively.
      Increasing VHb concentration to 3.8 mumol/g DCW suppressed the rate of carbon
      dioxide evolution in the exponential phase by 30%. A metabolic flux distribution
      analysis incorporating data from these cultivations discloses that VHb(+) cells
      direct a larger fraction of glucose toward the pentose phosphate pathway and a
      smaller fraction of carbon through the tricarboxylic acid cycle from acetyl
      coenzyme A. The overall nicotinamide adenine dinucleotide [NAD(P)H] flux balance
      indicates that VHb-expressing cells generate a net NADH flux by the NADH/NADPH
      transhydrogenase while the VHb(-) cells yield a net NADPH flux under the same
      growth conditions. Flux distribution analysis also reveals that VHb(+) cells have
      a smaller adenosine triphosphate (ATP) synthesis rate from substrate-level
      phosphorylation but a larger overall ATP production rate under microaerobic
      conditions. The thermodynamic efficiency of growth, based on reducing equivalents
      generated per unit of biomass produced, is greater for VHb(+) cells. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18623565
TI  - Intracellular expression of Vitreoscilla hemoglobin modifies microaerobic
      Escherichia coli metabolism through elevated concentration and specific activity
      of cytochrome o.
AB  - The function of the reversible oxygen-binding hemoprotein from Vitreoscilla
      (VHb), which enhances oxygen-limited cell growth and recombinant protein
      production when functionally expressed in Escherichia coli, was investigated in
      wild-type E. coli and in E. coli mutants lacking one of the two terminal
      oxidases, cytochrome o complex (aerobic terminal oxidase, Cyo) or cytochrome d
      complex (microaerobic terminal oxidase, Cyd). Deconvolution of VHb, cytochrome o,
      and cytochrome d bands from in vivo absorption spectra revealed a 5-fold
      enhancement in cytochrome o content and a 1.5-fold increment in cytochrome d by
      VHb under microaerobic environments (dissolved oxygen less than 2% air
      saturation). Based upon oxygen uptake kinetics measurements of these mutants, the
      apparent oxygen affinity of the Cyo(+), Cyd(-) E. coli was increased in the
      presence of VHb, but no difference in the apparent K(m) was observed for the Cyo(
      ), Cyd(+) strain. Results suggest that the expression of VHb in E. coli increases
      the level and activity of terminal oxidases and thereby improves the efficiency
      of microaerobic respiration and growth. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623566
TI  - Batch cultivation of Methylosinus trichosporium OB3b: V. Characterization of poly
      beta-hydroxybutyrate production under methane-dependent growth conditions.
AB  - Methanotrophs have promising applications in the bioremediation of chlorinated
      hydrocarbons and in the production of a biopolymer, poly-beta-hydroxybutyrate
      (PHB). Batch bioreactor culture conditions were studied for the accumulation of
      PHB by methane-grown Methylosinus trichosporium OB3b, and to evaluate the effect
      of PHB on the bacterial capacity to degrade trichloroethylene (TCE), a common
      groundwater contaminant. The PHB content of the washed and lyophilized cells was
      measured by gas chromatography (GC), after hydrochloric acid (HCl) propanolysis.
      A differential GC-based assay was developed for the monomer and the polymer of
      beta-hydroxybutyrate utilizing 1% and 10% HCl (v/v) reaction mixtures,
      respectively. During bioreactor growth in a Cu-deficient modified Higgins'
      medium, the cells accumulated PHB upon depletion of nitrate. A biomass yield of
      3.2 g dry wt/L and a PHB accumulation of approximately 10% (w/w) were reached
      after 140 to 160 h, without adversely affecting the propene or TCE epoxidation
      specific rate given by whole cells containing soluble methane monooxygenase
      (sMMO). The TCE biotransformation capacity ( approximately 0.25 mg TCE
      oxidized/mg dry cell wt) of resting cells containing approximately 10% PHB was
      consistently approximately 1.6-fold greater than that of cells containing only
      approximately 2% PHB. Higher levels (>10%) of accumulated PHB did not enhance
      this biotransformation capacity further. By replacing the bioreactor inlet air +
      CO(2) mixture with pure O(2) at approximately 85 h of batch operation, a PHB
      accumulation of approximately 45% was achieved after 160 h, but the whole-cell
      sMMO activity was markedly decreased. In contrast, cells grown in a 10 muM Cu
      supplemented Higgins' nitrate minimal salts medium (particulate MMO formation)
      accumulated up to 50% PHB in only 120 h, coupled with a very high biomass yield
      of 18 g dry cell wt/L. High PHB accumulations above approximately 20% by both the
      -Cu and the +Cu grown cells resulted in a decreased ratio of the electronic cell
      count to the absorbance at 660 nm, which is commonly used to monitor bacterial
      growth. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623567
TI  - Mathematical modeling of mixed-culture biofilms.
AB  - About 10 years ago a set of mass balance equations for mathematical modeling of
      mixed-culture biofilms (MCBs) was presented. That model was able to describe the
      progression of the biofilm thickness and the spatial distribution and development
      in time of particulate and dissolved components in the biofilm as a function of
      transport and transformation processes. Experimental observations made in the
      past years have shown that some of the assumptions made in that MCB model were
      too simple. Therefore, an extended MCB model with additional processes has been
      developed. This model includes a more flexible description of transport of
      dissolved components in the biofilm and considers diffusive transport of
      particulate components in the biofilm solid matrix, changes of the biofilm liquid
      phase volume fraction (porosity), and simultaneous detachment and attachment of
      cells and particles at the biofilm surface. The extended MCB model is implemented
      in AQUASIM, a new computer program designed for the analysis of aquatic systems,
      which is used here to illustrate and discuss the effect of the additional
      processes on MCB behavior. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623568
TI  - Improvement of antibiotic titers from Streptomyces bacteria by interactive
      continuous selection.
AB  - We have applied a technique of interactive continuous selection (ICS) to the
      isolation of streptomycin-resistant mutants of the streptomycin-producing
      organism, Streptomyces griseus. A series of mutants, each with a different
      colonial morphology and expressing successively greater resistance to
      streptomycin, was isolated during the course of selection. Takeover of the
      mutants has been correlated with changes in on-line estimates of streptomycin
      concentration such that these estimates may be used as a real-time measure of the
      genetic state of the cell population. When grown in the medium employed for ICS,
      mutants expressed increased antibiotic production titers; the best mutant
      produced 10 to 20 times more streptomycin than the parent strain. Absolute
      improvements in the maximum specific growth rate and intrinsic resistance to
      streptomycin did not account for the observed growth advantage of all mutants.
      Rather, each mutant exhibited relative increases in specific growth rate at
      increasing concentrations of streptomycin. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623569
TI  - A catalytic multistage fixed-bed tower bioreactor in an industrial-scale pilot
      plant for alcohol production.
AB  - This article describes the development of an industrial-scale, multistage fixed
      bed tower (MFBT) bioreactor using the promoter mineral kissiris for industrial
      alcohol production using free cells. Specifically, we examined the parameters
      needed to maintain operational stability from batch to batch for long periods.
      Pilot plant operations used one- and two-stage fixed-bed, 7000-L bioreactors.
      Likewise a 100,000-L, multistage fixed-bed tower system containing layered
      kissiris confirmed the laboratory results. Compared with a continuous stirred
      tank fermentor (CSTF) with recycle, a 30% reduction of energy demand and 10%-20%
      of the production costs are obtained. The latter are attributed to the increased
      ethanol concentration and alcohol productivity. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623570
TI  - Ion exchange purification of G6PDH from unclarified yeast cell homogenates using
      expanded bed adsorption.
AB  - The use of expanded beds of STREAMLINE ion exchange adsorbents for the direct
      extraction of an intracellular enzyme glucose-6-phosphate dehydrogenase (G6PDH)
      from unclarified yeast cell homogenates has been investigated. It has been
      demonstrated that such crude feedstocks can be applied to the bed without prior
      clarification steps. The purification of G6PDH from an unclarified yeast
      homogenate was chosen as a model system containing the typical features of a
      direct extraction technique. Optimal conditions for the purification were
      determined in small scale, packed bed experiments conducted with clarified
      homogenates. Results from these experiments were used to develop a preparative
      scale separation of G6PDH in a STREAMLINE 50 EBA apparatus. The use of an on-line
      rotameter for measuring and controlling the height of the expanded bed when
      operated in highly turbid feedstocks was demonstrated. STREAMLINE DEAE has been
      shown to be successful in achieving isolation of G6PDH from an unclarified
      homogenate with a purification factor of 12 and yield of 98% in a single step
      process. This ion exchange adsorbent is readily cleaned using simple cleaning-in
      place procedures without affecting either adsorption or the bed expansion
      properties of the adsorbent after many cycles of operation. The ability of
      combining clarification, capture, and purification in a single step will greatly
      simplify downstream processing flowsheets and reduce the costs of protein
      purification. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623571
TI  - Enzymatic synthesis of 2-beta-D-galactopyranosyloxy ethyl methacrylate (GalEMA)
      by the thermophilic archeon Sulfolobus solfataricus.
AB  - beta-Glycosidases catalyze the synthesis of glycosides when a nucleophilic
      acceptor other than water is present in the reaction medium. We describe the
      enzymatyc synthesis of 2-beta-D-galactopyranosyloxyethyl methacrylate (GalEMA)
      starting from 2-hydroxyethyl methacrylate (HEMA) and p-nitrophenyl-beta-D
      galactopyranoside (pNPG) using a beta-glycosidase activity present in the
      thermophilic archaeon Sulfolobus solfataricus. This thermophilic enzyme catalyzes
      the transfer of the galactopyranosyl unit from pNPG to the HEMA hydroxyl group by
      the formation of a new beta-glycosidic bond. The conditions of the biocatalytic
      system have been optimized to obtain high yield of GalEMA. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18623572
TI  - A simple correlation for predicting effective diffusivities in immobilized cell
      systems.
AB  - A simple correlation method has been developed to predict effective diffusivities
      of small molecules in heterogeneous materials such as immobilized cell systems.
      This correlation uses a single diffusivity measurement at one cell volume
      fraction to predict diffusivities for any other volume fraction of cell. The
      method has been applied to 20 sets of published diffusivity measurements in
      immobilized cell systems and accurately predicts affective diffusivities of
      molecules for the full range of cell fractions. It may also be used to predict
      effective diffusivities in heterogeneous materials in which the diffusivity of a
      molecule in each phase and the volume fraction of each phase are known. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18623574
TI  - Granular sludge formation in upflow anaerobic sludge blanket (UASB) reactors.
AB  - The state of the art for upflow anaerobic sludge blanket (UASB) reactors is
      discussed, focusing on the microbiology of immobilized anaerobic bacteria and the
      mechanism of granule formation. The development of granular sludge is the key
      factor for successful operation of the UASB reactors. Criteria for determining if
      granular sludge has developed in a UASB reactor is given based on the densities
      and diameters of the granular sludge. The shape and composition of granular
      sludge can vary significantly. Granules typically have a spherical form with a
      diameter from 0.14 to 5 mm. The inorganic mineral content varies from 10 to 90%
      of the dry weight of the granules, depending on the wastewater composition etc.
      The main components of the ash are calcium, potassium, and iron. The
      extracellular polymers in the granular sludge are important for the structure and
      maintenance of granules, while the inorganic composition seems to be of less
      importance. The extracellular polymer content varies between 0.6 and 20% of the
      volatile suspended solids and consists mainly of protein and polysaccharides.
      Both Methanosaeta spp. (formerly Methanothrix) and Methanosarcina spp. have been
      identified as important aceticlastic methanogens for the initial granulation and
      development of granular sludge. Immunological methods have been used to identify
      other methanogens in the granules. The results have showed that, besides the
      aceticlastic methanogens Methanosaeta spp. and Methanosarcina spp., hydrogen and
      formate utilizing bacteria are also present, e.g., Methanobacterium formicicum,
      Methanobacterium thermoautotrophicum, and Methanobrevibacter spp. Microcolonies
      of syntrophic bacteria are often observed in the granules, and the significant
      electron transfer in these microcolonies occurs through interspecies hydrogen
      transfer. The internal organization of the various groups of bacteria in the
      granules depends on the wastewater composition and the dominating metabolic
      pathways in the granules. Internal organization is observed in granules where
      such an arrangement is beneficial for an optimal degradation of the wastewater. A
      four-step model is given for the initial development of granular sludge. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18623575
TI  - Optimization of nonlinear biotechnological processes with linear programming:
      Application to citric acid production by Aspergillus niger.
AB  - The metabolic pathway and the properties of many of the enzymes involved in the
      citric acid biosynthesis in the mold Aspergillus niger are well known. This fact,
      together with the availability of new theoretical frameworks aimed at
      quantitative analyses of control and dynamics in metabolic systems, has allowed
      us to construct a mathematical model of the carbohydrate metabolism in
      Aspergillus niger under conditions of citric acid accumulation. The model makes
      use of the S-system representation of biochemical systems, which renders it
      possible to use linear programming to optimize the process. It was found that
      maintaining the metabolite pools within narrow physiological limits (20% around
      the basal steady-state level) and allowing the enzyme concentrations to vary
      within a range of 0.1 to 50 times their basal values it is possible to triple the
      glycolytic flux while maintaining 100% yield of substrate transformation. To
      achieve these improvements it is necessary to modulate seven or more enzymes
      simultaneously. Although this seems difficult to implement at present, the
      results are useful because they indicate what the theoretical limits are and
      because they suggest several alternative strategies. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18623576
TI  - Rat hepatocyte morphology and function on lactose-derivatized polystyrene
      surfaces.
AB  - Hepatocytes isolated from male Fisher 344VF rats were cultured on two substrates,
      collagen I and a lactose-derivatized polystyrene (PS-lactose), to compare
      morphological and functional differences. Hepatocyte morphology changed
      dramatically depending upon the substrate, shown through actin cytoskeletal
      staining and scanning electron microscopy. Functional assays performed included
      albumin secretion, reduced glutathione content, UDP-glucuronosyl transferase, and
      cytochrome P4501A1 activity. The presence of dexamethasone and dimethylsulfoxide
      (DMSO) in the media was required for the maintenance of several differentiated
      functions for cells cultured on collagen. In general, cells cultured on the PS
      lactose substrate showed a much slower loss of function over the same period of
      time. The maintenance of differentiated function of cells on PS-lactose was
      enhanced with the addition of dexamethasone and DMSO. This is the first report of
      a culture system in which hepatocytes, cultured on a polymer substrate without
      additional protein coatings or media additives, have been able to maintain
      differentiated functions for up to 1 week. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623577
TI  - Morphology and physiology of an alpha-amylase producing strain of Aspergillus
      oryzae during batch cultivations.
AB  - The microscopic morphology, that is, total hyphal length and total number of
      tips, has been characterized during batch cultivations of Aspergillus oryzae. The
      specific growth rate estimated by measuring the total hyphal length (mu(h))
      corresponds well with the specific growth rate estimated from dry weight
      measurements during cultures grown as free hyphal elements. The average tip
      extension rate can be described with a saturation type kinetics with respect to
      the average total hyphal length, and the branching frequency is closely related
      to the total hyphal length. For the applied strain of A. oryzae, pellet formation
      occurs by coagulation of spores. The agglomeration process is pH dependent and
      pellets are formed at pH values higher than 5, whereas low pH (<3.5) results in
      growth as freely dispersed hyphal elements. The maximum specific growth rate has
      a broad pH optimum between 3 and 7, whereas the alpha-amylase production has a
      sharper maximum at about pH 6. During batch cultivation with pellets the growth
      is described well by the cube-root law when pellet fragmentation can be
      neglected. The kinetic parameter k in the cube-root law is derived from the
      growth kinetics with no mass transfer limitation, k = mu(h)/3. Based on an oxygen
      balance, the active growth layer in the pellet is estimated to be 200 to 325 mum
      and, consequently, up to 50% of the biomass is limited by oxygen for large
      pellets. Ethanol production (up to 1 g L(-1)) was observed during batch
      cultivations with pellets, suggesting that ethanol is produced in the oxygen
      limited part of the biomass. A constitutive, low alpha-amylase production was
      observed at high glucose concentration. The specific alpha-amylase production was
      significantly higher for filamentous growth than for pellets and oxygen appears
      to be necessary for production of alpha-amylase. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623578
TI  - On-line estimation of viable cells in a hybridoma culture at various DO levels
      using ATP balancing and redox potential measurement.
AB  - Two on-line methods for the estimation of viable cell number in hybridoma
      cultivation were investigated. One used an empirical correlation between redox
      potential and animal cell density. The other was based on an ATP balance with ATP
      steady-state assumption. Oxygen uptake rate measurement provided the amount of
      ATP which was produced by oxidation of NADH. Oxygen uptake rate was measured
      either by stationary liquid phase balance with surface aeration or by gas balance
      during bubble aeration with headspace flushing with an inert gas. The amount of
      ATP produced through the glycolysis was estimated based on the amount of lactate
      produced. In cultures, in which pH was controlled via manipulation of the gas
      phase composition, the flow of CO(2) was linearly correlated with the lactate
      concentration. At constant dissolved oxygen levels, the viable cell density was
      proportional to the estimated ATP production rate, during exponential growth and
      during later phases. The estimated specific ATP production rate, however, varied
      from 2.2 pmol cell(-1) h(-1) at 10% air saturation to 4.5 pmol cell(-1) h(-1) at
      100% air saturation. Specific rates of glutamine, glucose, and lactate followed
      the shape of the specific ATP production rate, whereas the specific oxygen uptake
      rate was minimal at around 50% air saturation. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623579
TI  - Continuous in situ water activity control for organic phase biocatalysis in a
      packed bed hollow fiber reactor.
AB  - Packed bed hollow fiber membrane reactors were used to carry out organic phase
      biocatalysis at constant water activity. The performance of the device was tested
      by carrying out the esterification of dodecanol and decanoic acid in hexane.
      Lipase from Candida rugosa, immobilized on microporous polypropylene and packed
      in the shell space of the reactor, was used to catalyze the reaction. In situ
      water activity control was accomplished by pumping appropriate saturated salt
      solutions through the microporous hollow fiber polypropylene membranes. Water
      generated by reaction in the organic phase, pumped continuously through the shell
      of the reactor, was transferred into the bulk of the aqueous phase under the
      water activity gradient. The reactor performance was found to be strongly
      dependent on the controlling water activity. By carefully selecting this control
      activity it was found possible to obtain complete esterification. The water
      activity of the organic phase could be maintained very close to that of the
      saturated salt solution used. The reactor could be operated in the continuous
      mode for 100 h without any degradation in its performance. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18623580
TI  - Conservative chemical modification of proteins to study the effects of a single
      protein property on partitioning in aqueous two-phase systems.
AB  - Relatively conservative modifications of three proteins were carried out to alter
      their surface properties. The protein properties modified were hydrophobicity and
      charge. This was done by acylation of amino groups with anhydrides. For the
      hydrophobic modification experiments, two proteins (beta-lactoglobulin and bovine
      serum albumin [BSA]) and four anhydrides (hexanoic, butyric, succinic, acetic)
      were used. For the modification of surface charge the protein thaumatin was
      selected and various proportions of the free amino groups were blocked with
      acetic anhydride to give a series of proteins with differing isoelectric points.
      Detailed characterization and purification of selected modified proteins was
      carried out including molecular weight measurements and conformational analysis.
      The criteria used for selecting the modified proteins for subsequent
      investigation of their partitioning in aqueous two-phase systems (ATPS) is
      described. With a judicious choice of starting material it was found that limited
      chemical modifications to proteins could effectively alter surface hydrophobicity
      or charge almost independently, with little effect on other molecular properties.
      It appears, however, that the method for chemical modification and the reaction
      conditions must also be carefully controlled. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623581
TI  - Use of chemically modified proteins to study the effect of a single protein
      property on partitioning in aqueous two-phase systems: Effect of surface
      hydrophobicity.
AB  - Two different series of hydrophobically modified proteins were partitioned in a
      number of aqueous two-phase systems (ATPS) to investigate the effect of
      hydrophobicity as a single property on partitioning. The modified proteins were
      derived from beta-lactoglobulin and bovine serum albumin (BSA). Measurement of
      the surface hydrophobicity of the proteins is important; hydrophobic interaction
      chromatography (HIC) was used for this purpose. The resolution of the systems (R)
      in terms of protein surface hydrophobicity and the intrinsic hydrophobicity (log
      P(0)) of the systems was established. The effect of the addition of NaCl to
      PEG/phosphate and PEG/dextran systems was analyzed in terms of the hydrophobicity
      difference between the phases and their ability to promote hydrophobic
      interactions between the protein surface and the PEG molecules. The values for R
      and log P(0) differed somewhat depending on which group of modified proteins was
      used for partitioning. The addition of NaCl to PEG/phosphate systems promoted an
      increase in the values of R, showing an important effect on the resolution of the
      systems for protein surface hydrophobicity (twice as high when compared with
      systems without NaCl). For PEG/dextran systems, the addition of 9% NaCl (w/w)
      promoted an improvement in the resolution toward surface hydrophobicity with an
      increase of 60% on the value of R. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623582
TI  - Use of chemically modified proteins to study the effect of a single protein
      property on partitioning in aqueous two-phase systems: Effect of surface charge.
AB  - A series of charge-modified thaumatins with different values of surface charge
      were partitioned in aqueous two-phase systems (ATPS) to study the effect of
      surface charge as a single property on partitioning. Electrophoretic mobility of
      the proteins in titration curves was used as a measure of surface charge. Four
      modified proteins derived from thaumatin with the following values of isoelectric
      point: 8.70, 8.15, 5.60, and 4.50 were used for partitioning. The resolution of
      the systems in terms of protein surface charge was calculated. Partitioning of
      modified thaumatins in PEG 4000/dextran systems with phosphate buffer, Tris
      buffer, NaCl, KCl, and sulfate salts was carried out. Among the sulfate salts
      tested, the addition of 50 mM Li(2)SO(4) to the system buffered with phosphate
      gave the highest value of resolution for differences in surface protein charge
      (RSPC). It shows a decrease in the value of K (partition coefficient) with an
      increase in the protein's charge. The addition of 100 mM KCl to the system
      promoted the opposite effect on the RSPC value. Charge-modified proteins were
      partitioned in PEG/salt systems to investigate the ability of these systems for
      resolving differences in surface charge. The PEG/citrate system seemed to have
      almost no ability for resolving proteins on the basis of surface charge
      differences; PEG/phosphate systems had some capability for resolving differently
      charged proteins. The more negative proteins tended to have higher values of K
      than the more positively charged fractions. The use of charge-modified proteins
      allowed the investigation of the effect of protein surface charge on partitioning
      in aqueous two-phase systems independently from other protein parameters as they
      were prepared from a common parent protein thaumatin. This technique provides an
      interesting novel tool to investigate the effect of protein surface charge on
      partitioning in ATPS taking protein charge as an independent parameter. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18623583
TI  - In vivo investigations of glucose transport in Saccharomyces cerevisiae.
AB  - In the present study, the glucose transport into the yeast Saccharomyces
      cerevisiae has been investigated. The approach suggested is based on a rapid
      sampling technique for studying the dynamic response of the yeast to rapid
      changes in extracellular glucose concentrations. For this purpose a concentrated
      glucose solution has been injected into a continuous culture at steady state
      growth conditions resulting in a shift of the extracellular glucose level.
      Samples have been taken every 5 s for determination of extracellular glucose and
      intracellular glucose-6-phosphate concentrations. Attempts to fit the
      experimental observations with simulations from existing models failed. The
      mechanism then proposed is based on a facilitated diffusion of glucose
      superimposed by an inhibition of glucose-6-phosphate. The use of the so-called in
      vivo approach suggested in this article appears to be proper, because the
      investigations can be performed at defined physiological states of the microbial
      cultures. Furthermore, the experimental observations are not being corrupted by
      the preparation of the samples for the transport studies as it happens during
      radioactive measurements. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623584
TI  - Regioselective acylation of disaccharides in tert-butyl alcohol catalyzed by
      Candida antarctica lipase.
AB  - The acylation of several disaccharides by ethyl butanoate and ethyl dodecanoate
      was catalyzed by Candida antarctica lipase in tert-butyl alcohol, at temperatures
      ranging from 40 degrees to 82 degrees C (reflux temperature). The relative
      reaction rates of the various disaccharides were directly related to their
      solubility. The primary products were the monoesters derived from acylation of
      the primary alcohol groups. At higher conversions diesters were formed, and the
      ratio of diester to monoester was markedly dependent on the structure of the
      disaccharide. Thus, reaction of maltose with ethyl dodecanoate in refluxing tert
      butyl alcohol afforded the 6'-monododecanoate even at high conversions.
      Trehalose, in contrast, afforded the 6,6'-diester. Acylation of the less soluble
      sucrose and lactose was much slower, but a moderate (37%) conversion of sucrose
      was observed after a prolonged reaction time (7 days). A number of other lipases
      and proteases were tested but C. antarctica lipase was unique in catalyzing the
      acylation of sucrose in refluxing tert-butyl alcohol. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18623585
TI  - Growth kinetics of Lactobacillus acidophilus under ohmic heating.
AB  - Lactobacillus acidophilus OSU133 was inoculated into MRS broth in a fermenter
      vessel and incubated at 30, 35, or 45 degrees C with agitation. Incubation
      temperatures were attained by conventional or ohmic heating. An electrical
      current at low (15 V) or high (40 V) voltage was used to heat the culture
      directly during fermentations under ohmic heating. The growth parameters (lag
      period, minimum generation time, and maximum growth) and changes in pH were
      determined during fermentation. Metabolic activities (consumption of glucose and
      production of lactic acid and bacteriocin) were determined during fermentation at
      35 degrees C under both heating methods. Lag period for L. acidophilus was
      affected appreciably by the method of heating, but the magnitude of these changes
      depended on the fermentation temperature. When fermentation was done at 30
      degrees C, lag period decreased by 94% under low-voltage ohmic, compared with
      conventional, heating methods. Ohmic heating did not change the generation time
      significantly and caused slight, but significant (p < 0.01) decrease in maximum
      growth. Therefore, the electric current enhances the early stages, but it
      inhibits the late stages of growth. Ohmic, compared with conventional, heating
      resulted in higher final pH and lower bacteriocin activity in the fermented
      medium. However, ohmic heating at 35 degrees C had minimal effect on glucose
      utilization and lactic acid production by L. acidophilus. Results show that
      measurement of the electric current when ohmic heating is done at a constant
      voltage may be used in monitoring such fermentations. In conclusion, ohmic
      heating is potentially useful in certain applications related to fermented foods.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18623586
TI  - Water reuse in the L-lysine fermentation process.
AB  - L-Lysine is produced commercially by fermentation. As is typical for fermentation
      processes, a large amount of liquid waste is generated. To minimize the waste,
      which is mostly the broth effluent from the cation exchange column used for l
      lysine recovery, we investigated a strategy of recycling a large fraction of this
      broth effluent to the subsequent fermentation. This was done on a labscale
      process with Corynebacterium glutamicum ATCC 21253 as the l-lysine-producing
      organism. Broth effluent from a fermentation in a defined medium was able to
      replace 75% of the water for the subsequent batch; this recycle ratio was
      maintained for three sequential batches without affecting cell mass and l-lysine
      production. Broth effluent was recycled at 50% recycle ratio in a fermentation in
      a complex medium containing beet molasses. The first recycle batch had an 8%
      lower final l-lysine level, but 8% higher maximum cell mass. In addition to
      reducing the volume of liquid waste, this recycle strategy has the additional
      advantage of utilizing the ammonium desorbed from the ion-exchange column as a
      nitrogen source in the recycle fermentation. The major problem of recycling the
      effluent from the complex medium was in the cation-exchange operation, where
      column capacity was 17% lower for the recycle batch. The loss of column capacity
      probably results from the buildup of cations competing with l-lysine for binding.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18623587
TI  - A versatile oxygenator and perfusion system for magnetic resonance studies.
AB  - A compact, reusable membrane oxygenator has been constructed for the perfusion of
      cultured cells and isolated organs. While the oxygenator was designed to be
      compatible with nuclear magnetic resonance (NMR) spectroscopy studies, it can
      also be used for any experiment which requires warming and oxygenation of
      perfusates. For the NMR studies, the oxygenator can be positioned at the opening
      of the magnet bore which allows oxygenation and warming of the perfusate
      immediately prior to delivery to the tissue, therefore eliminating problems with
      heat or oxygen loss which may occur with the long perfusion lines. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18623589
TI  - Immobilization of trypsin onto "molded" macroporous poly(glycidyl methacrylate-co
      ethylene dimethacrylate) rods and use of the conjugates as bioreactors and for
      affinity chromatography.
AB  - Trypsin immobilization onto continuous "molded" rods of porous poly(glycidyl
      methacrylate-co-ethylene dimethacrylate) and some applications of the conjugate
      have been studied. The rods polymerized within a tubular mold (chromatographic
      column), were treated in situ with ethylenediamine, activated with glutaraldehyde
      and finally modified with trypsin. The performance of the trypsin-modified rods
      was evaluated and compared to that of poly(glycidyl methacrylate-co-ethylene
      dimethacrylate) beads, modified with the same enzyme. Overall the enzyme-modified
      rods performed substantially better than the corresponding beads. In particular,
      the performance of the molded supports as enzymatic reactors or as
      chromatographic media benefits greatly from the enhanced mass transfer that is
      characteristic of the molded rod at high flow rates. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18623590
TI  - Classification, error detection, and reconciliation of process information in
      complex biochemical systems.
AB  - Bioprocess identification starts with collection of process information. Usually
      there is a variety of information available, consisting of actual measurement
      data, historical data, empirical kinetic and yield correlations, and general
      knowledge available from literature. A central problem is to find out how the
      various pieces of information should be integrated. In addition, one should know
      how to deal with missing, inconsistent, or too inaccurate data. Recently, a
      general systematic method for dealing with these problems, based on conservation
      constraints, was published, and application shown to simple black box systems. In
      this article, the scope is generalized by including metabolic network data and
      dispersed process information of diverse type and nature, such as multiple
      sources of the value of one particular quantity, use of kinetic expressions,
      analytical problems, cometabolism or mixed substrate utilization, and chemical
      reactions. The alkalophilic bacterium Acinetobacter calcoaceticus is used as a
      model organism, growing on acetate and converting xylose into xylonolactone. It
      is shown that all relevant pieces of information can be straightforwardly and
      systematically treated, by considering them as constaints. In general, it is
      illustrated how the search for directed process improvements starts with an
      optimal selection of information sources, followed by an accurate analysis of
      possible metabolic bottlenecks. In this particular case it is shown that the
      yield of A. calcoaceticus on acetate at varying xylose/acetate feed ratios can be
      accurately predicted using dispersed process information. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18623591
TI  - Dichloroacetate increases cell and antibody yields in batch cultures of a
      hybridoma cell line.
AB  - We have studied the effect of the pyruvate dehydrogenase (PDH) activator,
      dichloroacetate (DCA), on the growth, metabolism, and productivity of the PQXB
      (1/2) hybridoma cell line. In control batch cultures, cessation of growth and the
      onset of decline phase coincided with the time at which the media became
      exhausted of glutamine. Supplementation of the media with DCA (1 mM) extended the
      growth phase of this cell line by approximately 20 h without affecting its growth
      rate. This prolonged period of growth resulted in an increased maximum cell
      density (16%) and final antibody yield (55%). Repeat experiments showed these
      effects to be reproducible, with the increases in antibody yield being between 50
      and 60%. DCA did not affect the specific rates of glucose utilization and lactate
      production. However, it decreased the specific glutamine consumption rate. This
      characteristic of DCA action appeared, at least in part, to provide an
      explanation for the extended growth phase exhibited by DCA-treated cultures,
      since it delayed the time at which the media became depleted of glutamine. The
      consumption and production kinetics for various nutrients and their metabolites
      in both control and DCA-treated cultures suggested that: (1) glutamine catabolism
      proceeded by a pathway involving conversion to glutamate by glutaminase followed
      by subsequent transamination by alanine aminotransferase, and (2) DCA decreased
      the specific glutamine consumption rate by directly or indirectly inhibiting the
      transamination. It is expected that the routine inclusion of DCA in media used
      for hybridoma cultivation will be valuable for enhancement of monoclonal antibody
      (Mab) yields on a laboratory scale. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623592
TI  - Fluid shear stress induction of the transcriptional activator c-fos in human and
      bovine endothelial cells, HeLa, and Chinese hamster ovary cells.
AB  - The c-fos protein belongs to a family of transcriptional cofactors that can
      complex with proteins of the Jun family and activate mRNA transcription from gene
      promoters containing an activator protein 1 (AP-1) binding element. The shear
      stress inducibility of the c-fos protein was studied in human and animal cell
      lines of vastly different origins. Primary human umbilical vein endothelial cells
      (HUVEC), bovine aortic endothelial cells (BAEC, passage 2-14), HeLa cells, and
      Chinese hamster ovary (CHO) cells were subjected to steady laminar shear stress
      using a parallel plate flow apparatus. After 1 h of flow exposure at 25
      dyn/cm(2), the c-fos levels in nuclei of shear stress HUVEC, BAEC, HeLa, and CHO
      were 5.4 +/- 2.0 (n = 3), 2.25 +/- 1.38 (n = 6), 2.14 +/- 0.07 (n = 8), 1.92 +/-
      0.58 (n = 2) times higher, respectively, than in matched stationary controls.
      Flow exposure at 4 dyn/cm(2) caused no enhancement of c-fos levels in any of the
      cell lines tested, but caused significant reduction in c-fos expression in the
      HeLa cells. The c-fos induction by shear stress could be blocked by
      pharmacological agents. For example, the flow induction of the c-fos protein
      levels was blocked by 50% with the preincubation of HUVEC with a protein kinase C
      inhibitor, H7 (10 muM) and blocked completely in HeLa cells preincubated with the
      phospholipase C inhibitor, neomycin (5 mM). The minimum time of shear stress
      exposure required to induce the c-fos protein expression in HeLa cells was found
      to be as low as 1 min. By Northern analysis, the c-fos mRNA levels were found to
      be elevated in BAEC, CHO, and HeLa cells exposed to 25 dyn/cm(2) for 30 min.
      These studies indicate that c-fos induction is a consistent genetic response in a
      variety of mammalian cells that may alter cellular phenotype in mechanical
      environments. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623593
TI  - Macro-kinetic investigation on phenol uptake from air by biofiltration: Influence
      of superficial gas flow rate and inlet pollutant concentration.
AB  - The macro-kinetic behavior of phenol removal from a synthetic exhaust gas was
      investigated theoretically as well as experimentally by means of two identical
      continuously operating laboratory-scale biological filter bed columns. A mixture
      of peat and glass beads was used as filter material. After sterilization it was
      inoculated with a pure strain of Pseudomonas putida, as employed in previous
      experimental studies. To determine the influence of the superficial gas flow rate
      on biofilter performance and to evaluate the phenol concentration profiles along
      the column, two series of continuous tests were carried out varying either the
      inlet phenol concentration, up to 1650 mg . m(-3), or the superficial gas flow
      rate, from 30 to 460 m(3) . m(-2) . h(-1). The elimination capacity of the
      biofilter is proved by a maximum volumetric phenol removal rate of 0.73 kg . m(
      3) . h(-1). The experimental results are consistent with a biofilm model
      incorporating first-order substrate elimination kinetics. The model may be
      considered a useful tool in scaling-up a biofiltration system. Furthermore, the
      deodorization capacity of the biofilter was investigated, at inlet phenol
      concentrations up to 280 mg . m(-3) and superficial gas flow rates ranging from
      30 to 92 m(3) . m(-2) . h(-1). The deodorization of the gas was achieved at a
      maximum inlet phenol concentration of about 255 mg . m(-3), operating at a
      superficial gas flow rate of 30 m(3) . m(-2) . h(-1). (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18623594
TI  - Solvent effects on the catalytic activity of subtilisin suspended in compressed
      gases.
AB  - We studied a model transesterification reaction catalyzed by subtilisin Carlsberg
      suspended in carbon dioxide, propane, and mixtures of these solvents under
      pressure. To account for solvent effects due to differences in water partitioning
      between the enzyme and the bulk solvents, we measured water sorption isotherms
      for the enzyme in each solvent. We measured catalytic activity as a function of
      enzyme hydration and obtained bell-shaped curves with maxima at the same enzyme
      hydration (12%) in all the solvents. However, the activity maxima were different
      in all media, being much higher in propane than in either CO(2) or the mixtures
      with 50 and 10% CO(2). Considerations based on the solvation ability of the
      solvents did not offer an explanation for the differences in catalytic activity
      observed. Our results suggest that CO(2) has a direct adverse effect on the
      catalytic activity of subtilisin. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623595
TI  - Protein precipitation by caprylic acid: Equilibrium composition data.
AB  - The precipitation equilibria of hen egg-white lysozyme and bovine serum albumin
      from aqueous solutions by caprylic acid were studied. A thermodynamic equilibrium
      was obtained, and the compositions of both the precipitate and the aqueous phases
      were measured to establish phase diagrams for both systems. The precipitate was
      not pure protein, but also contained large amounts of water and caprylic acid. At
      constant initial pH and ionic strength, the composition of both phases depended
      only on the overall composition of the system. This suggests that protein
      precipitation by fatty acids should be pictured as liquid-liquid rather than
      solid-liquid equilibria. The precipitated proteins retained high biological
      activity. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623596
TI  - Vancomycin production in batch and continuous culture.
AB  - Production of the glycopeptide antibiotic vancomycin by two Amycolatopsis
      orientalis strains was examined in batch shake flask culture in a semidefined
      medium with peptone as the nitrogen source. Different growth and production
      profiles were observed with the two strains; specific production (Y(p/x)) was
      threefold higher with strain ATCC 19795 than with strain NCIMB 12945. A defined
      medium with amino acids as the nitrogen source was developed by use of the
      Plackett-Burman statistical screening method. This technique identified certain
      amino acids (glycine, phenylalanine, tyrosine, and arginine) that gave
      significant increased specific production, whereas phosphate was identified as
      inhibitory for high specific vancomycin production. Experiments made with the
      improved medium and strain ATCC 19795 showed that vancomycin production kinetics
      were either growth dissociated or growth associated, depending on the amino acid
      concentration. In chemostat culture at a constant dilution rate (0.087 h(-1)),
      specific vancomycin production rate (q(vancomycin)) decreased linearly as the
      medium phosphate concentration was increased from 2 to 8 mM. In both phosphate
      and glucose limited chemostats, q(vancomycin) was a function of specific growth
      rate; the maximum value was observed at D = 0.087 h(-1) (52% of the maximum
      specific growth rate). Under phosphate limited growth conditions, q(vancomycin)
      was threefold higher (0.37 mg/g dry weight/h) than under glucose limitation (0.12
      mg/g dry weight/h). (c) 1996 John Wiley & Sons, Inc.

PMID- 18623597
TI  - Effect of glucose supply strategy on acetate accumulation, growth, and
      recombinant protein production by Escherichia coli BL21 (lambdaDE3) and
      Escherichia coli JM109.
AB  - Two Escherichia coli strains, widely used for the production of various
      recombinant proteins, were compared for their pre-induction growth and acetate
      accumulation patterns. The strains studied were E. coli BL21 (lambdaDE3),
      transformed with a plasmid encoding Pseudomonas exotoxin A, and an E. coli K12
      derived strain, JM109, carrying a plasmid encoding maltose-binding protein fused
      with HIV protease. Cultures were grown in controlled bench-top fermentors to the
      optimal pre-induction density in both high glucose batch and low glucose fed
      batch strategies. The results showed the superiority of E. coli BL21 (lambdaDE3)
      as a host for a recombinant protein expression system. For example, JM109
      responds differently to high glucose concentration and to low glucose
      concentration. Its acetate concentration was as high as 10 g/L in a batch mode
      and 5 g/L in a fed batch mode. In comparison, strain BL21 (lambdaDE3) reached 2
      g/L acetate when grown in batch mode and not more than 1 g/L acetate when grown
      in a fed batch mode. E. coli BL21 (lambdaDE3), most likely, possesses an acetate
      self-control mechanism which makes it possible to grow to the desired pre
      induction density in a high glucose medium using simple batch propagation
      techniques. Such a technique is cost effective, reproducible, and easy to scale
      up. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623598
TI  - Kinetic evaluation of biotransformation of benzaldehyde to L-phenylacetylcarbinol
      by immobilized pyruvate decarboxylase from Candida utilis.
AB  - Biotransformation of benzaldehyde to L-phenylacetylcarbinol (L-PAC) as a key
      intermediate for L-ephedrine has been evaluated using immobilized pyruvate
      decarboxylase (PDC) from Candida utilis. PDC immobilized in spherical
      polyacrylamide beads was found to have a longer half-life compared with free
      enzyme. In a batch process, the immobilized PDC generally produced lower L-PAC
      than free enzyme at the same concentrations of substrates due to increased by
      products acetaldehyde and acetoin and reduced benzaldehyde uptake. With
      immobilized PDC, L-PAC formation occurred at higher benzaldehyde concentrations
      (up to 300 mM) with the highest L-PAC concentration being 181 mM (27.1 g/L). For
      a continuous process, when 50 mM benzaldehyde and 100 mM sodium pyruvate were fed
      into a packed-bed reactor at 4 degrees C and pH 6.5, a productivity of 3.7 mM/h
      (0.56 g/L . h) L-PAC was obtained at an average concentration of 30 mM (4.5 g/L).
      The half-life of immobilized PDC reactor was 32 days. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18623599
TI  - Maximum virginiamycin production by optimization of cultivation conditions in
      batch culture with autoregulator addition.
AB  - A strategy for optimization of non-growth-associated production in batch culture
      employing an empirical approach was developed through the study of virginiamycin
      production. The strategy is formulated with two aims: attaining a high cell
      concentration at the beginning of the production phase without decrease in
      production activity; and enhancing the production activity during the production
      phase. As a practical example, the goal of a maximum virginiamycin (M and S)
      production in the batch culture of Streptomyces virginiae was set. To attain a
      high cell concentration in the production phase of the batch culture, that is, to
      extend the growth phase for as long as possible, the optimum composition and
      concentration of the complex medium, especially the yeast extract (YE)
      concentration, were first investigated. Dissolved oxygen (DO) concentration
      control was also a parameter considered in maintaining the production activity
      during the production phase. In addition, to enhance the production activity, an
      optimum addition strategy of an autoregulator, virginiae butanolide-C (VB-C), was
      investigated. Combining these measures, the optimum cultivation conditions were
      found to be an initial YE concentration in the complex medium of 45 g/L, the shot
      addition of 300 mug/L of VB-C 11.5 h after the start of the batch culture, and a
      DO concentration maintained above 2 mg/L. The maximum concentrations of
      virginiamycin M and S were about ninefold those obtained under nonoptimum
      cultivation conditions. Nonoptimum cultivation conditions consisted of an initial
      YE concentration one sixth (7.5 g/L) that of the optimum cultivation conditions,
      and no VB-C addition. These conditions were used as representative of the
      standard cultivation of virginiamycin in this study. The strategy developed here
      will be applicable to the production of other antibiotics, especially to the
      cultivation of Streptomyces species, in which a hormonelike signal material (an
      autoregulator) plays an important role in antibiotic production. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18623600
TI  - Modeling biocide action against biofilms.
AB  - A phenomenological model of biocide action against microbial biofilms was
      derived. Processes incorporated in the model include bulk flow in and out of a
      well-mixed reactor, transport of dissolved species into the biofilm, substrate
      consumption by bacterial metabolism, bacterial growth, advection of cell mass
      within the biofilm, cell detachment from the biofilm, cell death, and biocide
      concentration-dependent disinfection. Simulations were performed to analyze the
      general behavior of the model and to perform preliminary sensitivity analysis to
      identify key input parameters. The model captured several general features of
      antimicrobial agent action against biofilms that have been observed widely by
      experimenters and practitioners. These included (1) rapid disinfection followed
      by biofilm regrowth, (2) slower detachment than disinfection, and (3) reduced
      susceptibility of microorganisms in biofilms. The results support the
      plausibility of a mechanism of biofilm resistance in which the biocide is
      neutralized by reaction with biofilm constituents, leading to a reduction in the
      bulk biocide concentration and, more significantly, biocide concentration
      gradients within the biofilm. Sensitivity experiments and analyses identified
      which input parameters influence key response variables. Each of three response
      variables was sensitive to each of the five input parameters, but they were most
      sensitive to the initial biofilm thickness and next most sensitive to the biocide
      disinfection rate coefficient. Statistical regression modeling produced simple
      equations for approximating the response variables for situations within the
      range of conditions covered by the sensitivity experiment. The model should be
      useful as a tool for studying alternative biocide control strategies. For
      example, the simulations suggested that a good interval between pulses of biocide
      is the time to minimum thickness. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623601
TI  - Study of hydrodynamics in microcarrier culture spinner vessels: A particle
      tracking velocimetry approach.
AB  - Three-dimensional particle tracking velocimetry (3-D PTV), a modern,
      quantitative, visualization tool, has been applied to the characterization of the
      flow field in the impeller region of cell culture reactor vessels. The
      experimental system used here is a 250-mL microcarrier spinner vessel. The
      studies were conducted at three different agitation rates, 90, 150, and 210 rpm,
      corresponding to healthy, mildly damaging, and severely damaging shear
      intensities, respectively. The flow can be classified into three regions: a
      predominantly tangential (azimuthal) flow generated by the impeller; a trailing
      vortex region coming off the impeller tip; and a converging flow region close to
      the center of the vessel. The latter two are the regions of highest velocity
      gradients. Energy dissipation rates due to mean velocity gradients were also
      calculated to characterize the impeller stream. Local specific energy dissipation
      rates > 10,000 erg/(cm(3)sec) . have been measured. It is proposed that the
      critical regions for microcarrier culture damage due to impeller hydrodynamics
      are the trailing vortex region and the high energy converging flow region.
      Graphical representation of the mean velocity flow fields and the distribution of
      energy dissipation rates in the impeller region are also presented here. The
      merits of using the dissipation function (measure of specific energy dissipation
      rate) as a possible scale-up parameter are also discussed. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18623602
TI  - Correlation between secreted and membrane-bound IgG in mouse myeloma cells
      transfected with chimeric immunoglobulin heavy and light chain genes.
AB  - Mouse myeloma cells were transfected with pSV2-gpt and pSV2-neo based
      immunoglobulin expression vectors. Double transfectants were selected using the
      xanthine-guanine phosphoribosyl transferase (gpt) and the neomycin (neo)
      selection marker genes. A broad distribution in the level of mouse-human chimeric
      IgG expression was observed with series of independently isolated transfectoma
      clones. The relative amounts of secreted to membrane-bound antibodies correlated
      closely, which suggested, that fluorescence-activated cell sorting could be a
      valuable tool for the selection of high-yielding production cell lines. However,
      a single cycle of cell sorting did not steer the cloning process significantly
      toward cells that produce enhanced amounts of recombinant IgG. Only in cases in
      which the polyclonal transfectoma population contained a large percentage of
      nonproducing cells, these were successfully separated from the IgG-producing cell
      population. (c) 1996 John Wiley & Sons, Inc.

PMID- 18623603
TI  - Highly efficient secretion of heterologous proteins from Saccharomyces cerevisiae
      using inulinase signal peptides.
AB  - The INU genes of Kluyveromyces marxianus encode inulinases which are readily
      secreted from Saccharomyces cerevisiae into the culture medium. To evaluate the
      utility of the INU signal peptides for the secretion of heterologous proteins
      from S. cerevisiae, a variety of expression and secretion vectors were
      constructed with GAL10 promoter and GAL7 terminator. The coding sequence for
      human lipocortin-1 (LC1) was inserted in-frame with the INU signal sequences, and
      then the secretion efficiency and localization of LC1 were investigated in more
      detail and compared with those when being expressed by the vector with the
      MFalpha1 leader peptide. The vector systems with INU signal peptides secreted ca.
      95% of the total LC1 expressed into the extracellular medium, while the MFalpha1
      leader peptide-containing vector resulted in very low secretion efficiency below
      10%. In addition, recombinant human interleukin-2 (IL-2) was expressed and
      secreted with the vector systems with INU signal peptide, and a majority fraction
      of the human IL-2 expressed was found to be secreted into the extracellular
      medium as observed in LC1 expression. (c) 1995 John Wiley & Sons, Inc.

PMID- 18623604
TI  - On the use of the pH control reagent addition rate for fermentation monitoring.

PMID- 18623605
TI  - Pentachlorophenol decreases ATP levels in human natural killer cells.
AB  - Pentachlorophenol (PCP) is used as a wood preservative and is found in human
      blood and urine. PCP causes significant decreases in the tumor-killing (lytic)
      function of human natural killer (NK) cells, a critical immune defense. The
      current study examined the association between decreased lytic function and
      decreased ATP levels, as well as the ability of antioxidants (vitamin E and
      reduced glutathione) to prevent PCP-induced decreases in either ATP levels or
      lytic function. Exposure of NK cells to 10 microm PCP decreased ATP levels by 15%
      at 24 h, and exposure to 5 microm PCP decreased ATP levels by 32% at 48 h. No
      effects were seen with 0.5 microm at 48 h or with 5 microm at 24 h. However, 10
      microm PCP decreased lytic function by 69% at 24 h and 5 microm decreased it by
      90% at 48 h. Even 0.5 microm PCP decreased lytic function by 46% at 48 h. None of
      these effects were prevented by pretreatment with 1 mm vitamin E or reduced
      glutathione.

PMID- 18623606
TI  - Estimating local and global measures of association for bivariate interval
      censored data with a smooth estimate of the density.
AB  - Measures of association for bivariate interval censored data have not yet been
      studied extensively. Betensky and Finkelstein (Statist. Med. 1999; 18:3101-3109)
      proposed to calculate Kendall's coefficient of concordance using a multiple
      imputation technique, but their method becomes computer intensive for moderate to
      large data sets. We suggest a different approach consisting of two steps.
      Firstly, a bivariate smooth estimate of the density of log-event times is
      determined. The smoothing technique is based on a mixture of Gaussian densities
      fixed on a grid with weights determined by a penalized likelihood approach.
      Secondly, given the smooth approximation several local and global measures of
      association can be estimated readily. The performance of our method is
      illustrated by an extensive simulation study and is applied to tooth emergence
      data of permanent teeth measured on 4468 children from the Signal-Tandmobiel
      study.

PMID- 18623607
TI  - The meaning of work and working life after cancer: an interview study.
AB  - BACKGROUND: Cancer survivors have diverse and complex patterns of return to work,
      but little attention has been given to individual experiences of returning to
      work. OBJECTIVES: To analyse the meaning of work and working life for cancer
      survivors over time. METHODS: Participant observation was carried out at a cancer
      rehabilitation centre. A total of 23 participants were interviewed twice.
      RESULTS: Cancer survivors try to get back to work after treatment and try to re
      establish their former structure of everyday-life that is seen as a normal and
      healthy existence. Work contributes to creating the individual as a social being,
      partaking in social relations with others. Work plays a role in establishing the
      individual's identity. It is difficult for many to resume work. When they are
      unable to work, they establish new activities in everyday-life that give meaning
      to a life. In order to understand the cultural meaning of work in capitalist
      society, we incorporate the theoretical perspective of Max Weber. CONCLUSION:
      Those who after cancer treatment are unable to work lose a part of their
      identity; they lose the personal challenge and satisfaction related to work. They
      are no longer part of the companionship related to work. Having had cancer means
      a disruption of the structure of everyday-life that is taken for granted.

PMID- 18623608
TI  - Intention-to-treat analysis in cluster randomized trials with noncompliance.
AB  - In cluster randomized trials (CRTs), individuals belonging to the same cluster
      are very likely to resemble one another, not only in terms of outcomes but also
      in terms of treatment compliance behavior. Although the impact of resemblance in
      outcomes is well acknowledged, little attention has been given to the possible
      impact of resemblance in compliance behavior. This study defines compliance
      intraclass correlation as the level of resemblance in compliance behavior among
      individuals within clusters. On the basis of Monte Carlo simulations, it is
      demonstrated how compliance intraclass correlation affects power to detect
      intention-to-treat (ITT) effect in the CRT setting. As a way of improving power
      to detect ITT effect in CRTs accompanied by noncompliance, this study employs an
      estimation method, where ITT effect estimates are obtained based on compliance
      type-specific treatment effect estimates. A multilevel mixture analysis using an
      ML-EM estimation method is used for this estimation.

PMID- 18623610
TI  - Coculture of genetically transformed roots and shoots for synthesis,
      translocation, and biotransformation of secondary metabolites.
AB  - Genetically transformed shooty teratomas of Atropa belladonna and a Duboisia
      leichhardtii x D. myoporoides hybrid were studied for biotransformation of
      tropane alkaloids in shake flasks and bioreactors. Although de novo synthesis of
      hyoscyamine and scopolamine was limited, shoots of both species were able to
      translocate and accumulate significant quantities of exogenous alkaloid. The
      maximum yield of scopolamine from hyoscyamine fed to the Duboisia hybrid shoots
      was 35% w/w; the yield of the scopolamine precursor, 6beta-hydroxyhyoscyamine,
      was 37% w/w. Biotransformation activity was poor in A. belladonna shooty
      teratomas provided with exogenous hyoscyamine; however, scopolamine levels
      comparable with those in leaves of the whole plant accumulated in shoots fed with
      hairy root extract. Coculture of A. belladonna shooty teratomas and hairy roots
      in the same hormone-free medium was investigated as a means of providing a
      continuous source of hyoscyamine for conversion to scopolamine. Of the
      biotransformation systems tested with A. belladonna, coculture produced the
      highest levels of scopolamine and the highest scopolamine: hyoscyamine ratios.
      Cocultured shoots accumulated up to 0.84 mg g(-1) dry weight scopolamine, or 3-11
      times the average concentrations found in leaves of the whole plant. The
      scopolamine: hyoscyamine ratio in coculture ranged from 0.07 to 1.9, a
      significant improvement over levels of 0-0.03 normally found in A. belladonna
      hairy roots. Addition of Pluronic F-68 or copper sulfate to the medium and
      variation in initial medium pH did not improve hyoscyamine release from hairy
      roots. Scopolamine levels were increased using 1 microM copper sulfate or initial
      medium pH between 6.0 and 8.0; however, results from elicitation of hairy roots
      could not match the beneficial effect on scopolamine synthesis of root-shoot
      coculture. Addition of 0.001-1.0% (w/v) Pluronic F-68 to the roots reduced
      hyoscyamine release but postponed necrosis in the root tissue for up to 60 d.

PMID- 18623611
TI  - Synthesis of poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) by recombinant
      Escherichia coli.
AB  - Several recombinant Escherichia coli strains, including XL1-Blue, JM109, HB101,
      and DH5alpha harboring a stable high-copynumber plasmid pSYL105 containing the
      Alcaligenes eutrophus polyhydroxyalkanoate (PHA) biosynthesis genes were
      constructed. These recombinant strains were examined for their ability to
      synthesize and accumulate poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co
      3HV)] copolymer from glucose and either propionate or valerate. All recombinant
      E. coli strains could synthesize the P(3HB-co-3HV) copolymer in the medium
      containing glucose and propionate. However, only the homopolymer poly-(3
      hydroxybutyrate) [P(3HB)] was synthesized from glucose and valerate. The PHA
      concentration and the 3HV fraction could be increased by inducing with acetate
      and/or oleate. When supplemented with oleate, the 3HV fraction increased by
      fourfold compared with that obtained without induction. Induction with propionate
      resulted in lower PHA concentration due to the inhibitory effect, but an 3HV
      fraction of as high as 33.0% could be obtained. These results suggest that P(3HB
      co-3HV) can be efficiently produced from propionate by recombinant E. coli by
      inducing with acetate, propionate, or oleate.

PMID- 18623612
TI  - Simultaneous saccharification and extractive fermentation of cellulosic
      substrates.
AB  - Alcohol fermentation has traditionally been carried out in aqueous environments
      because of the ready solubility of reactant (sugar) and product (ethanol).
      However, extraction of the product ethanol into a nonmiscible phase can result in
      kinetic benefits due to reduced inhibition of the fermentation reactions. In this
      study, we report the development of a novel simultaneous saccharification and
      extractive fermentation (SSEF) process. Ethanol productivity was increased by up
      to 65% over conventional (nonextractive) fed-batch simultaneous saccharification
      systems when calculated on the basis of aqueous phase volume. The amount of water
      required for SSEF reactions was dramatically reduced from that required for
      conventional SSF. In batch SSEF reactors with 2.5% aqueous phase, 50% conversion
      of 25% (aqueous phase concentration) Solka Floc could be achieved in 48 h using 2
      FPU/g cellulase.

PMID- 18623613
TI  - Development of operating conditions for protein purification using expanded bed
      techniques: the effect of the degree of bed expansion on adsorption performance.
AB  - A strategy for the optimization of an expanded bed adsorption process has been
      developed by studying a model system involving the adsorption of lysozyme onto
      the adsorbent STREAMLINE SP. The hydrodynamic and adsorption properties of this
      ion exchange adsorbent in a variety of viscosities of feedstocks have been
      compared by analyzing bed expansion characteristics, liquid phase dispersion
      characteristics, equilibrium adsorption isotherms, and mass transfer
      characteristics. Additionally, the influences of the degree of bed expansion on
      adsorption performance have been investigated by frontal analysis. In these
      experiments, viscous feedstocks were simulated by the inclusion of glycerol in
      the adsorption buffers. Breakthrough curves for lysozyme were characterized and
      compared in terms of overall purification processing time and productivity. On
      the basis of these results, the relative productivities of different operating
      modes with the same process liquid were found to be almost the same. However, the
      processing time for each purification cycle decreased with increasing velocity of
      process liquid. It is demonstrated that an adsorption process carried out at a
      constant degree of bed expansion (twice its settled bed height, corresponding to
      bed voidage of 0.7) is more efficient, when characterized by the apparent dynamic
      binding capacity, than operation at a constant liquid velocity of 300 cm/h. These
      results have significant implications on the design and operation of the expanded
      bed adsorption procedures. The advantages and problems encountered in the use of
      expanded bed techniques for the direct extraction of proteins from unclarified
      feedstocks are also discussed.

PMID- 18623614
TI  - Efficient immobilization of lipases by entrapment in hydrophobic sol-gel
      materials.
AB  - The commercial application of lipases as biocatalysts for organic synthesis
      requires simple but efficient methods to immobilize the enzyme, yielding highly
      stable and active biocatalysts which are easy to recover. In this study, we
      present a novel method to achieve lipase immobilization by entrapment in
      chemically inert hydrophobic silica gels which are prepared by hydrolysis of
      alkyl-substituted silanes in the presence of the enzyme. A typical immobilization
      procedure uses: an aqueous solution of lipase; sodium fluoride as a catalyst; and
      additives like polyvinyl alcohol or proteins and alkoxysilane derivatives like
      RSi-(OMe)(3) with R = alkyl, aryl, or alkoxy as gel precursors. The effect of
      various immobilization parameters like stoichiometric ratio of water, silane,
      type and amount of additive, type and amount of catalyst, and type of silane has
      been carefully studied. The new method is applicable for a wide variety of
      lipases, yielding immobilized lipases with esterification activities enhanced by
      a factor of up to 88, compared to the commercial enzyme powders under identical
      conditions. Studies on the stability of sol-gel immobilized lipases under
      reaction conditions or storage (dry, in aqueous or organic medium) revealed an
      excellent retention of enzymatic activity. The possible reasons for the increased
      enzyme activities are discussed.

PMID- 18623615
TI  - Microencapsulation of yeast cells and their use as a biocatalyst in organic
      solvents.
AB  - Stable, semipermeable polyamide microcapsules were prepared by interfacial
      polymerization from a mixture of 1,6-hexanediamine and poly(allylamine)
      crosslinked with di-acid chlorides and were used to encapsulate baker's yeast.
      The size and distribution of cells within the capsules were investigated by a
      combination of laser confocal, electron scanning, and transmission electron
      microscopy. The encapsulated cells were studied as a biocatalyst for the model
      reduction of 1-phenyl-1,2-propanedione to 2-hydroxy-1-phenyl-1-propanone in a
      number of organic solvents. The polymerization conditions were extensively
      investigated and were found to greatly influence the product yield.
      Microencapsulated yeast cells, prepared under optimized conditions, carried out
      the reduction more efficiently than free cells as well as those immobilized in
      alginate and kappa-carrageenan beads. The developed methodology should be broadly
      applicable to other biotransformations of interest.

PMID- 18623616
TI  - Behavior of glucose oxidase immobilized in various electropolymerized thin films.
AB  - Glucose oxidase was immobilized by electropolymerization into films of
      polyaniline, polyindole, polypyrrole, poly(o-phenylediamine), and polyaniline
      crosslinked with p-phenylenediamine. The kinetics and the behavior of the
      entrapped enzyme toward elevated temperature, organic solvent denaturation, and
      pH were investigated, along with the response of the films to electroactive
      species such as acetaminophen, ascorbate, cysteine, and uric acid. For most of
      the films, linearity to glucose extended from 7 to 10 mM. The poly(o
      phenylenediamine)/glucose oxidase film gave the best signal/noise ratio and
      polypyrrole/glucose oxidase film gave the most reproducible current responses. No
      significant shift of the optimum reaction pH (5.5), except for polypyrrole (5.0),
      was observed after immobilization of glucose oxidase in the various films.
      Enzymatic activity decreased rapidly when pH was raised above 7.5.
      Thermodeactivation studies at 55 degrees , 60 degrees , and 65 degrees C have
      shown polypyrrole/and poly(o-phenylediamine)/glucose oxidase films to be the most
      resistant enzymatic films. Poly(o-phenylenediamine) films offered the best
      protection against glucose oxidase deactivation in hexane, chloroform, ether,
      THF, and acetonitrile when compared with the other electropolymerized films. All
      the enzymatic films exhibited permselection toward electroactive species.

PMID- 18623617
TI  - Nucleophile specificity of subtilisin in an organic solvent with low water
      content: investigation via acyl transfer reactions.
AB  - Nucleophile specificity of subtilisin (subtilopeptidase A) was studied via acyl
      transfer reactions in acetonitrile containing piperidine and 10 vol% of water. Ac
      Tyr-OEt was used as acyl donor and a series of amino acid derivatives, di- and
      tripeptides of the general structure Xaa-Gly, Gly-Xaa, Gly-Gly-Xaa (Xaa
      represents all natural L-amino acids except cysteine) were used as nucleophiles.
      The nucleophilic efficiencies of these peptides were characterized by the values
      of the apparent partition constants, p(app), determined from the HPLC analysis of
      the reactions. The order of preference for the P'(1) position was estimated to
      be: Gly > hydrophilic, positively charged > hydrophobic, aromatic > negatively
      charged > Leu >>> Pro side chain. For the P'(2) position the order of preference
      was: Gly > hydrophilic, charged > hydrophobic, aromatic > Pro side chain. The
      values of p(app) for Gly-Gly-Xaa tripeptides cover a range of only two orders of
      magnitude, with lower nucleophile efficiency for those with hydrophobic amino
      acid residues in the P'(3) position. The dipeptide with Pro in P'(1) did not
      react at all, but a tripeptide having Pro in P'(3) was a very good nucleophile.
      The negatively charged amino acid residues in the P'(1) position result in very
      weak nucleophilic behavior, whereas the peptides with Asp or Glu in P'(2) and
      P'(3) are well accepted. Generally, peptides of the Gly-Xaa or Gly-Gly-Xaa series
      were better nucleophiles than peptides of the Xaa-Gly series. The length of the
      peptide chain or amidation of alpha-carboxyl function had no influence on
      nucleophilic behavior. No significant difference in nucleophile specificity
      between subtilopeptidase A and nagarse was observed.

PMID- 18623618
TI  - Development and bioreactor cultivation of a novel semidifferentiated tissue
      suspension derived from the marine plant Acrosiphonia coalita.
AB  - A semidifferentiated tissue culture consisting of linear filaments in liquid
      suspension was established from Acrosiphonia coalita, a cold-water green
      macroalga known to express pharmacologically active oxylipins deriving from
      lipoxygenase metabolism of linolenic acid. The tissue was vegatively propagated
      by blending the filaments down to 1 to 5 mm in length prior to subculture. The
      filamentous A. coalita tissue suspension was successfully cultivated in an
      illuminated, 3-L stirred-tank bioreactor at 12 degrees C, 0.46-vvm aeration rate,
      250-rpm mixing speed, and incident illumination intensity of 77 microE m(-2)s(
      1). The mean specific growth rate over the exponential phase was 0.185 day(-1)
      and a final cell density of 1083 mg dry cell weight (DCW) L(-1) was achieved
      within 15 days of cultivation from an initial cell density of 200 mg DCW L(-1).
      The addition of 3500 ppm CO(2) to the aeration gas provided a maximum CO(2)
      transfer rate of six times the maximum CO(2) consumption rate and stabilized the
      pH to 8.0 during the light phase of growth, but did not improve biomass
      productivity.

PMID- 18623619
TI  - Pretreatment of wheat straw using combined wet oxidation and alkaline hydrolysis
      resulting in convertible cellulose and hemicellulose.
AB  - The wet oxidation process of wheat straw has been studied as a pretreatment
      method to attain our main goal: To break down cellulose to glucose enzymatic, and
      secondly, to dissolve hemicellulose (e.g., for fermentation) without producing
      microbial inhibitors. Wet oxidation combined with base addition readily oxidizes
      lignin from wheat straw facilitating the polysaccharides for enzymatic
      hydrolysis. By using a specially constructed autoclave system, the wet oxidation
      process was optimized with respect to both reaction time and temperature. The
      best conditions (20 g/L straw, 170 degrees C, 5 to 10 min) gave about 85% w/w
      yield of converting cellulose to glucose. The process water, containing dissolved
      hemicellulose and carboxylic acids, has proven to be a direct nutrient source for
      the fungus Aspergillus niger producing exo-beta-xylosidase. Furfural and
      hydroxymethyl-furfural, known inhibitors of microbial growth when other
      pretreatment systems have been applied, were not observed following the wet
      oxidation treatment.

PMID- 18623620
TI  - Continuous culture study of the expression of hepatitis B surface antigen and its
      self-assembly into virus-like particles in Saccharomyces cerevisiae.
AB  - We have studied the growth rate dependence of hepatitis B surface antigen (HBsAg)
      p24(s) monomer and lipoprotein particle synthesis produced in Saccharomyces
      cerevisiae using galactose-limited continuous culture. The hepatitis B virus S
      gene, which encodes the p24(s) monomer, is transcribed under the control of the
      GAL 10p on a chimeric 2-microm plasmid harbored in a haploid yeast strain.
      Monomers autonomously form lipoprotein aggregates (particles) in vivo using only
      host-cell-derived components. Steady states were evaluated in a range from 0.015
      h(-1) to washout (0.143 h(-1)). Both p24(s) monomer and HBsAg particle levels, at
      steady state, varied in an inverse linear manner with growth rate. A consistent
      excess of total p24(s) monomer to HBsAg particle, estimated at five- to tenfold
      by mass, was found at all dilution rates. The average copy number of the 2-microm
      plasmid (carrying LEU2 selection) remained constant at 200 copies per cell from
      washout to 0.035 h(-1). Surprisingly, the average copy number was undetectable at
      the lowest dilution rate tested (0.015 h(-1)), even though HBsAg expression was
      maximal. Total p24(s) monomer and HBsAg particle values ranged twofold over this
      dilution rate range. No differences in the trends for HBsAg expression and
      average copy number could be detected past the critical dilution rate where
      aerobic fermentation of galactose and ethanol overflow were observed. HBsAg
      expression in continuous culture was stable for at least 40 generations at 0.100
      h(-1).

PMID- 18623621
TI  - Transient-state behavior of a biofilter removing mixtures of vapors of MEK and
      MIBK from air.
AB  - In the work reported here, selected aspects of the dynamic behavior of biofilters
      for waste air treatment have been investigated. Emphasis was placed on transient
      state elimination of mixtures of methyl ethyl ketone (MEK) and methyl isobutyl
      ketone (MIBK) vapors and on explanation of the observed phenomena. The initial
      startup, the response of the biofilter to step changes in the pollutant loadings,
      responses to pollutant pulses, restarting after starvation, and the influence of
      step changes in gaseous phase oxygen partial pressure are presented and
      discussed.

PMID- 18623622
TI  - Application of probe electrospray to direct ambient analysis of biological
      samples.
AB  - Recently, we have developed probe electrospray ionization (PESI) that uses a
      solid needle. In this system, the probe needle moves up and down along the
      vertical axis by a motor-driven system. At the highest position of the probe
      needle, electrospray is generated by applying a high voltage. In this study, we
      applied PESI directly to biological samples such as urine, mouse brain, mouse
      liver, salmon egg, and fruits (orange, banana, etc.). Strong ion signals for
      almost all the samples were obtained. The amount of liquid sample picked up by
      the needle is as small as pL or less, making PESI a promising non-invasive
      technique for detecting biomolecules in living systems such as cells. Therefore,
      PESI may be useful as a versatile and ready-to-use semi-online analytical tool in
      the fields of medicine, pharmaceuticals, agriculture, food science, etc.

PMID- 18623624
TI  - Beyond rocket science.

PMID- 18623623
TI  - Heterogeneity of kinase inhibitor resistance mechanisms in GIST.
AB  - Most GIST patients develop clinical resistance to KIT/PDGFRA tyrosine kinase
      inhibitors (TKI). However, it is unclear whether clinical resistance results from
      single or multiple molecular mechanisms in each patient. KIT and PDGFRA mutations
      were evaluated in 53 GIST metastases obtained from 14 patients who underwent
      surgical debulking after progression on imatinib or sunitinib. To interrogate
      possible resistance mechanisms across a broad biological spectrum of GISTs, inter
      and intra-lesional heterogeneity of molecular drug-resistance mechanisms were
      evaluated in the following: conventional KIT (CD117)-positive GISTs with KIT
      mutations in exon 9, 11 or 13; KIT-negative GISTs; GISTs with unusual morphology;
      and KIT/PDGFRA wild-type GISTs. Genomic KIT and PDGFRA mutations were
      characterized systematically, using complementary techniques including D-HPLC for
      KIT exons 9, 11-18 and PDGFRA exons 12, 14, 18, and mutation-specific PCR (V654A,
      D820G, N822K, Y823D). Primary KIT oncogenic mutations were found in 11/14
      patients (79%). Of these, 9/11 (83%), had secondary drug-resistant KIT mutations,
      including six (67%) with two to five different secondary mutations in separate
      metastases, and three (34%) with two secondary KIT mutations in the same
      metastasis. The secondary mutations clustered in the KIT ATP binding pocket and
      kinase catalytic regions. FISH analyses revealed KIT amplicons in 2/10 metastases
      lacking secondary KIT mutations. This study demonstrates extensive intra- and
      inter-lesional heterogeneity of resistance mutations and gene amplification in
      patients with clinically progressing GIST. KIT kinase resistance mutations were
      not found in KIT/PDGFRA wild-type GISTs or in KIT-mutant GISTs showing unusual
      morphology and/or loss of KIT expression by IHC, indicating that resistance
      mechanisms are fundamentally different in these tumours. Our observations
      underscore the heterogeneity of clinical TKI resistance, and highlight the
      therapeutic challenges involved in salvaging patients after clinical progression
      on TKI monotherapies.

PMID- 18623625
TI  - Simultaneous single-tube PCR-based assay for the direct identification of the
      five most common meningococcal serogroups from clinical samples.
AB  - This study presents a stepdown multiplex PCR assay for the simultaneous detection
      of the five most common Neisseria meningitidis serogroups (A, B, C, W-135 and Y)
      in 530 clinical samples obtained from 428 patients (271 blood and 259
      cerebrospinal fluid). The sensitivity and the specificity was calculated to 100%
      [positive predictive value 100% (95%, CI 99.0-100%) and negative predictive value
      100% (95% CI 99.0-100%)]. The overall effectiveness permits the rapid, accurate
      and inexpensive detection of the five most prevalent meningococcal serogroups in
      clinical samples. It is potentially a valuable tool for diagnosis and
      epidemiological monitoring of disease due to N. meningitidis.

PMID- 18623626
TI  - [Transvertebral Ventilation].

PMID- 18623627
TI  - Reply to OCD letter.

PMID- 18623628
TI  - Questionable inflated estimate of smoking prevalence among mentally ill persons
      in Australia.

PMID- 18623630
TI  - [No information about roseroot in hypertension].

PMID- 18623629
TI  - NIX induces mitochondrial autophagy in reticulocytes.
AB  - The controlled elimination of defective mitochondria is necessary for the health
      of long-lived post-mitotic cells, like cardiomyocytes and neurons. Mitochondrial
      elimination also occurs during the course of normal development, in lens
      epithelial and erythroid cells. Strikingly, at the final stage of erythroid cell
      maturation, newly formed erythrocytes, also known as reticulocytes, eliminate
      their entire cohort of mitochondria. We have employed this model to investigate
      the mechanism of programmed mitochondrial clearance. NIX (BNIP3L) is a Bcl-2
      related protein that is upregulated during terminal erythroid differentiation.
      NIX-deficient reticulocytes have a significant defect of mitochondrial clearance.
      Consistent with the ability of NIX to cause mitochondrial depolarization, we show
      that mitochondria are depolarized in wild type but not NIX deficient
      reticulocytes. NIX does not function through established proapoptotic pathways,
      nor does it mediate the induction of autophagy in erythroid cells. Rather, NIX is
      required for the selective incorporation of mitochondria into autophagosomes.
      Elucidation of the mechanism of this effect will improve our understanding of the
      role of autophagy in the maintenance of cellular homeostasis.

PMID- 18623631
TI  - [Role of gamma-interferon in the immunopathogenesis of infections].

PMID- 18623633
TI  - Some Incidental Observations on the Possibility of a Virus as Part Causal Factor
      in Rheumatism.

PMID- 18623632
TI  - [Antioxidative defense parameters in acute and chronic cholecystitis].
AB  - A hundred and fifty-two patients cholelithiasis were examined. Among them, 69 and
      83 patients were operated on for acute destructive and chronic cholecystitis,
      respectively. In destructive cholecystitis, there is a high lipid oxidation rate
      accompanied by the elevated levels of nonenzymatic antioxidant ceruloplasmin. The
      low activity of catalase and ceruloplasmin and the decreased content of ascorbic
      acid suggest the depletion of antioxidative defense in patients with
      cholelithiasis with significant liver disease. The magnitude of changes in the
      activity of antioxidative enzymes and the level of the nonenzymatic antioxidant
      ascorbic acid depend on the state of the liver.

PMID- 18623634
TI  - A Virus in Rheumatism.

PMID- 18623635
TI  - The Identification of the Haemolytic Streptococci, with Special Reference to
      those of the Upper Respiratory Tract.

PMID- 18623636
TI  - Observations on the Pathology of Acute Rheumatism and Rheumatoid Arthritis.

PMID- 18623637
TI  - A Contribution to the Pathology of the Rheumatoid Type of Arthritis and of
      Rheumatic Fever (Abstract).

PMID- 18623638
TI  - Experimental Fibrositis due to a Virus, and Some Observations on the Experimental
      Production of Arthritis.

PMID- 18623639
TI  - Heberden's Nodes in a Girl of Fifteen Years of Age.

PMID- 18623640
TI  - Recent Researches on Arthritis and Rheumatism in the United States.

PMID- 18623641
TI  - Preliminary Observations on the Oxygen and Carbon Dioxide Gas Tensions in the
      Knee-Joint in Normal and Pathological Conditions.

PMID- 18623642
TI  - The AEtiological Problem of Rheumatism.

PMID- 18623643
TI  - Researches into the AEtiology of Acute Rheumatism: I. Rheumatic Carditis: Post
      Mortem Investigation of Nine Consecutive Cases.

PMID- 18623645
TI  - The Rheumatic Nodules in the Heart.

PMID- 18623644
TI  - The Influence of Morphological Structure on the Pathology of Joints.

PMID- 18623646
TI  - A Review of Recent Italian Work on Rheumatism: I.-Rheumatic Fever.

PMID- 18623648
TI  - Rheumatic Subcutaneous Nodule Formation.

PMID- 18623647
TI  - The Formol-Gel Reaction and Erythrocyte Sedimentation Rate in Acute Rheumatism.

PMID- 18623649
TI  - The Sociological Aspects of the Treatment of Arthritis: Notes on a Visit to the
      United States.

PMID- 18623650
TI  - Juvenile Rheumatism in London.

PMID- 18623651
TI  - The Treatment of the Rheumatic Diseases in the United States and the Continent of
      Europe.

PMID- 18623652
TI  - Gout an Unsolved Problem.

PMID- 18623653
TI  - The Effect of Chrysotherapy on the Sedimentation Rate in Rheumatoid Arthritis.

PMID- 18623654
TI  - The Erythrocyte Sedimentation Test: A Wide-Bore Tube Method Using Oxalated Blood
      And Permitting Correction of the Result to a Standard Red-Cell Volume.

PMID- 18623655
TI  - An Index of the Sedimentation Rate on a Mathematical Basis.

PMID- 18623656
TI  - A Review of Recent Italian Work on Rheumatism : II.-Chronic Rheumatism.

PMID- 18623657
TI  - Recent Investigations on Rheumatism and Arthritis in the United States.

PMID- 18623658
TI  - Tuberculin Reactions in Ankylosing Spondylitis Compared with those in other
      Rheumatic Diseases.

PMID- 18623659
TI  - Splenectomy in the Treatment of Rheumatoid arthritis : A Report of Three Cases.

PMID- 18623661
TI  - Fibrositis and Pain.

PMID- 18623660
TI  - The Spontaneous Polyarthritis of Rats and the Syndrome Induced by Inoculation of
      Human Material in these Animals.

PMID- 18623662
TI  - Differential Diagnosis of Periarticular Fibrositis and Arthritis.

PMID- 18623663
TI  - Infection and Fibrositis.

PMID- 18623664
TI  - Laboratory Findings in Fibrositis.

PMID- 18623665
TI  - Traumatic Fibrositis.

PMID- 18623666
TI  - The Arthritic Sequelae of Pneumatic Drilling.

PMID- 18623668
TI  - Editorial.

PMID- 18623667
TI  - Streptococcal Antifibrinolysin in Rheumatoid Arthritis and Spondylitis
      Ankylopoietica.

PMID- 18623670
TI  - Fibrositis: Some Old and New Points of View.

PMID- 18623669
TI  - The Treatment of Sciatica, Brachialgia, and Occipital Headache.

PMID- 18623671
TI  - The Nature of Fibrositis and the Influence of Psychological States upon it.

PMID- 18623672
TI  - Editorial.

PMID- 18623673
TI  - The Present Status of the Ligue Internationale contre le Rhumatisme.

PMID- 18623674
TI  - Recent Studies on Arthritis and Rheumatism in the United States.

PMID- 18623675
TI  - A Study of Certain Blood Tests which reveal Colloidal Abnormalities in Rheumatic
      Conditions.

PMID- 18623676
TI  - Observations on Rheumatic Diseases under War Conditions.

PMID- 18623677
TI  - Observations on Respiration in Articular Cartilage.

PMID- 18623678
TI  - The Use of the Sulphonamide Group of Drugs in the Treatment of Tonsillitis due to
      the Beta-Haemolytic Streptococcus and in Acute Rheumatic Fever.

PMID- 18623680
TI  - The Weltmann Coagulation Reaction and the Sedimentation Test in Arthritis.

PMID- 18623679
TI  - An Epidemic Myalgia Distinct from Bornholm Disease, Which Chiefly Affected the
      Muscles of the Neck.

PMID- 18623681
TI  - A Specific Reaction in Acute Rheumatism and Rheumatoid Arthritis.

PMID- 18623682
TI  - Fractures in Chronic Arthritis.

PMID- 18623683
TI  - Gout and Male Pseudo-Hermaphrodism: Report of a Case.

PMID- 18623684
TI  - The War on Rheumatism.

PMID- 18623685
TI  - Haemolytic Streptococcal Infections and Acute Rheumatism.

PMID- 18623686
TI  - Generic and Specific Influences of Nutrition in the Total Support of Arthritics.

PMID- 18623687
TI  - Fibrositis: A Biographical Study of Fifty Civilian and Military Cases, from the
      Rheumatic Unit, St. Stephen's Hospital (London County Council), and a Military
      Hospital.

PMID- 18623688
TI  - Cultural Studies on Rheumatoid Arthritis and Rheumatic Fever.

PMID- 18623689
TI  - A Report on a Test of Mester's "Specific" Reaction in Rheumatic Cases.

PMID- 18623690
TI  - Five Hundred Cases of Myalgia in the British Army.

PMID- 18623691
TI  - Metabolism, Toxicity and Manner of Action of Gold Compounds used in the Treatment
      of Arthritis: Complete Excretion Studies and Comparison of Intravenous and
      Intramuscular administration of Some Gold Salts.

PMID- 18623692
TI  - Resistance in Rheumatism.

PMID- 18623693
TI  - Editorial.

PMID- 18623694
TI  - The Evaluation of the Roentgenologic Findings in Arthritis.

PMID- 18623695
TI  - Rheumatic Fever and nutrition.

PMID- 18623696
TI  - Visceral Lesions Associated with Rheumatoid Arthritis.

PMID- 18623697
TI  - Blood Cultures in Rheumatoid Arthritis: Historical and Personal Observations.

PMID- 18623699
TI  - An Analysis of 388 Cases of Rheumatoid Arthritis.

PMID- 18623698
TI  - Editorial.

PMID- 18623700
TI  - A Study of Liver Function and Plasma Volume in Chronic Rheumatism by Means of
      Phenol-Tetrabrom-Phthalein Sodium Sulphonate.

PMID- 18623701
TI  - A Clinical Contribution to the Study of the aetiology of the Fibrositic Nodule.

PMID- 18623702
TI  - New Paths of Investigation for Diagnosis and Therapy.

PMID- 18623703
TI  - Observations on the Natural History of Acute Rheumatic Fever.

PMID- 18623705
TI  - A Case of Tuberculous Rheumatism: Grocco-Poncet Type.

PMID- 18623704
TI  - Aspects of "Fibrositis".

PMID- 18623706
TI  - The Nodules and Lymph-Gland Enlargement in Rheumatoid Arthritis: Also a Syndrome
      of Rheumatoid Arthritis Combined with Multiple Xanthomatous Connective Tissue
      Infiltrations.

PMID- 18623707
TI  - Sciatica: An Anatomical and Mechanical Study of the Lumbosacral Region.

PMID- 18623708
TI  - Experimental Transmission of Rheumatic Fever.

PMID- 18623709
TI  - The Micro-Determination of Gold in Biological Fluids and Tissues.

PMID- 18623710
TI  - Determination of Blood Level of Vitamin C in Chronic Rheumatic Disease.

PMID- 18623712
TI  - Gout and its Effect on the Cardiovascular System.

PMID- 18623711
TI  - Fibrositis and Reality.

PMID- 18623713
TI  - Nerve Symptoms in Vertebral Rheumatism.

PMID- 18623714
TI  - Blood Plasma Fibrinogen in Rheumatic and Non-Rheumatic conditions.

PMID- 18623716
TI  - "A.C.B. Serum" of Prof. Bogomoletz in the Treatment of Rheumatism.

PMID- 18623715
TI  - Rheumatic Disease in the Middle East.

PMID- 18623717
TI  - Gold Treatment in Rheumatoid Arthritis.

PMID- 18623719
TI  - Investigation into the Aetiology and Pathology of Fibrositis of the Back.

PMID- 18623718
TI  - Effect of Penicillin on Rheumatoid Arthritis.

PMID- 18623720
TI  - Some Orthopaedic Aspects of Rheumatic Disease.

PMID- 18623721
TI  - Rheumatic Fever in Malta: A Clinical Note.

PMID- 18623722
TI  - The Nature of Fibrositis: I. The Myalgic Lesion and its Secondary Effects: a
      Reflex Theory.

PMID- 18623723
TI  - Observations on the Treatment of Rheumatic Fever with Vitamin P.

PMID- 18623724
TI  - A Benign Type of Rheumatic Fever.

PMID- 18623725
TI  - Rheumatism in Sweden.

PMID- 18623726
TI  - A Study of Rheumatism in a Group of Soldiers with Reference to the Incidence of
      Trigger Points and Fibrositic Nodules.

PMID- 18623727
TI  - Anatomy and Physiology of Diarthrodial Joints.

PMID- 18623728
TI  - Bacteriological Investigation of Air During an Epidemic of Haemolytic
      Streptococcal Throat Infection.

PMID- 18623729
TI  - Ankylosing Spondylitis: Its Aetiology and Pathology.

PMID- 18623730
TI  - Orthopaedic Aspects of Rheumatoid Arthritis.

PMID- 18623731
TI  - Return to Normal of X-Ray Changes in Rheumatoid Arthritis : Case Report.

PMID- 18623733
TI  - Ankylosing Spondylitis: Review.

PMID- 18623732
TI  - Rheumatoid Arthritis: Review.

PMID- 18623734
TI  - The Nature of Fibrositis: II. A Study of the Causation of the Myalgic Lesion.

PMID- 18623735
TI  - Weltmann Coagulation Reaction in Rheumatoid Arthritis.

PMID- 18623736
TI  - The Formol-Gel Test on Plasma and Serum in Rheumatic Cases: Correlation Studies
      and a Suggestion that Non-Rouleaux-Forming Pathological Globulins may be of
      Significance in Rheumatism.

PMID- 18623737
TI  - Necrobiotic Nodules of Rheumatoid Arthritis Type with Lipoid Deposition.

PMID- 18623738
TI  - Fibrositis and beta-Diethylaminoethyl Dehydrocholate.

PMID- 18623740
TI  - Editorial.

PMID- 18623739
TI  - Cold-Reaction Test for Peripheral Vasomotor Disturbances in Rheumatism.

PMID- 18623741
TI  - The Management of Chronic Arthritis and other Rheumatic Diseases among Soldiers
      of the United States Army.

PMID- 18623742
TI  - The Chronic Rheumatic Diseases in the World War 1939-1945.

PMID- 18623743
TI  - Chronic Rheumatic Diseases from the Services in E.M.S. Hospitals.

PMID- 18623744
TI  - Acute Rheumatism.

PMID- 18623745
TI  - Lesions in Muscle in Arthritis.

PMID- 18623746
TI  - Nodule Formation in Rheumatic Disease.

PMID- 18623748
TI  - The Nature of Fibrositis: III. Multiple Lesions and the Neural Hypothesis.

PMID- 18623747
TI  - Pleuropneumonia-Like Organisms and Arthritis.

PMID- 18623749
TI  - EPILOGUE TO THE SERIES ENTITLED "THE NATURE OF FIBROSITIS".

PMID- 18623750
TI  - The Incidence of Rheumatism.

PMID- 18623751
TI  - Review of Gout, 1939-1946.

PMID- 18623752
TI  - Editorial.

PMID- 18623754
TI  - Problem of Chronic Rheumatism.

PMID- 18623753
TI  - Organization of Rheumatism Research and Treatment in Sweden.

PMID- 18623755
TI  - Herniation of Subfascial Fat as a Cause of Low Back Pain: Report of Thirty-Seven
      Cases Treated Surgically.

PMID- 18623756
TI  - Discussion of the Paper by Ralph Herz : Herniation of Subfascial Fat as a Cause
      of Low Back Pain.

PMID- 18623757
TI  - Present Swiss Concepts of Rheumatism and Physical Medicine.

PMID- 18623758
TI  - Epidemic Myalgia affecting the Trapezius Muscle.

PMID- 18623759
TI  - Neostigmine Therapy in Rheumatoid Arthritis.

PMID- 18623760
TI  - X-ray Appearances in Chronic Rheumatism.

PMID- 18623761
TI  - Intestinal Extract in Rheumatic Diseases.

PMID- 18623762
TI  - Psychosomatic Non-Articular Rheumatism.

PMID- 18623763
TI  - Editorial.

PMID- 18623764
TI  - Spinal Osteoporosis, Cause Unknown.

PMID- 18623765
TI  - Generalized Osteoporosis in Old Age.

PMID- 18623767
TI  - "Standard Bone": A Description of Radiographic Technique.

PMID- 18623768
TI  - Psychogenic Rheumatism: The Musculoskeletal Expression of Psychoneurosis.

PMID- 18623766
TI  - Review of the Literature on Acute Rheumatism During the Years 1939-1945.

PMID- 18623770
TI  - A Case of Calcinosis Circumscripta.

PMID- 18623769
TI  - Psychogenic Arthralgia.

PMID- 18623771
TI  - Significance of Subcutaneous Nodules in Rheumatoid Arthritis.

PMID- 18623772
TI  - Hypersensitivity to Colchicine.

PMID- 18623773
TI  - Agglutination of Haemolytic Streptococci (Group A) in Serum from Patients with
      Rheumatoid Arthritis.

PMID- 18623774
TI  - Aetiology of Fibrositis: A Review.

PMID- 18623775
TI  - Heberden's Nodes: The Clinical Characteristic Of Osteo-Arthritis Of The Fingers.

PMID- 18623776
TI  - Pain in the Arm: A Review.

PMID- 18623777
TI  - A Controlled Series of Cooke-Arneth Polynuclear Counts in Rheumatoid Arthritis.

PMID- 18623778
TI  - The Phosphatase Activity in Spondylitis Ankylopoietica.

PMID- 18623779
TI  - The Necrobiotic Nodules of Rheumatoid Arthritis: Case in Which the Scalp,
      Abdominal Wall (Involving Striped Muscle), Larynx, Pericardium (Involving
      Myocardium), Pleurae (Involving Lungs), and Peritoneum were Affected.

PMID- 18623780
TI  - Investigations into the Effect of Hot, Dry Microclimate on Peripheral
      Circulation, etc., in Arthritic Patients.

PMID- 18623781
TI  - Flocculation Tests in Rheumatoid Arthritis.

PMID- 18623782
TI  - Interstitial Neuritis and the Neural Theory of Fibrositis.

PMID- 18623783
TI  - The Relation of the Cardiac Lesions of Rheumatoid Arthritis to those of Rheumatic
      Fever.

PMID- 18623784
TI  - Idiopathic Extreme Osteoporosis, Especially of the Spinal Column and Thoracic
      Cage, with Collapse of Front of Chest.

PMID- 18623785
TI  - Muscle Histology in Rheumatic and Control Cases: A Study of One Hundred and
      Nineteen Biopsy Specimens.

PMID- 18623786
TI  - Bal in the Treatment of Gold Toxicity.

PMID- 18623787
TI  - On the Occurrence of Neuropathic Arthropathies in Pernicious Anaemia.

PMID- 18623788
TI  - Palindromic Rheumatism.

PMID- 18623789
TI  - The Gross Anatomy of the Peri-Articular Tissues of the Shoulder Joint.

PMID- 18623791
TI  - The Problem of Arthritis in Switzerland.

PMID- 18623790
TI  - A Check on the Anatomical Accuracy of Intra-Articular Hip Injections in Relation
      to the Therapy of Coxarthritis.

PMID- 18623792
TI  - A Variant of Rheumatoid Arthritis resembling Palindromic Rheumatism.

PMID- 18623793
TI  - Metabolism of Hyaluronic Acid in Relation to Rheumatic Diseases.

PMID- 18623794
TI  - Synovial Fluid Mucin.

PMID- 18623795
TI  - Histopathology of the Intrinsic Muscles of the Hand in Rheumatoid Arthritis.

PMID- 18623796
TI  - Clinical Significance and Treatment of Lesions of the Intervertebral Disk.

PMID- 18623797
TI  - Treatment of So-called Palindromic Rheumatism with Gold Compounds.

PMID- 18623799
TI  - Rheumatological Hand and Finger Symptoms.

PMID- 18623798
TI  - Rheumatoid Arthritis and Psoriasis.

PMID- 18623801
TI  - Salicylate Therapy in Rheumatic Fever.

PMID- 18623800
TI  - Drugs in the Treatment of Rheumatic Disorders.

PMID- 18623802
TI  - Thiouracil, etc. in Experimental Polyarthritis.

PMID- 18623803
TI  - Copper and Gold Salts in Rheumatoid Arthritis.

PMID- 18623804
TI  - Serum Anti-Tryptase in Chronic Rheumatic Disease.

PMID- 18623805
TI  - Familial Incidence of Rheumatoid Spondylitis.

PMID- 18623806
TI  - Aetiology of Ankylosing Spondylitis.

PMID- 18623807
TI  - Opaque Arthrography of the Knee Joint.

PMID- 18623808
TI  - Rheumatoid Arthritis and Amyloid Disease.

PMID- 18623810
TI  - Editorial.

PMID- 18623809
TI  - Generalized Myositis Fibrosa.

PMID- 18623811
TI  - Potential Reversibility of Rheumatoid Arthritis.

PMID- 18623812
TI  - The effect of a hormone of the adrenal cortex (17-hydroxy-11
      dehydrocorticosterone: compound E) and of pituitary adrenocortical hormone in
      arthritis: preliminary report.

PMID- 18623813
TI  - Subcutaneous Nodules of Rheumatoid Arthritis with Lipoid Deposition.

PMID- 18623814
TI  - Can the Defence Mechanism of the Body be Influenced by Roentgen Irradiation?:
      Report on a Preliminary Clinical Investigation of the Plasma or Serum Protein
      Pattern in Rheumatoid Arthritis.

PMID- 18623815
TI  - Focal Infection in Rheumatoid Arthritis: A Comparison of the Incidence of Foci of
      Infections in the Upper Respiratory Tract in One Hundred Cases of Rheumatoid
      Arthritis and One Hundred Controls.

PMID- 18623816
TI  - Plasma Viscosity.

PMID- 18623817
TI  - Early Symptoms of Rheumatoid Arthritis.

PMID- 18623818
TI  - Cervical Sympathetic Block in Periarthrosis of the Shoulder Joint with Secondary
      Reflex Dystrophy.

PMID- 18623819
TI  - Estimation of Gold in Biological Fluids.

PMID- 18623820
TI  - Salazopyrin in the Treatment of Rheumatoid Arthritis.

PMID- 18623821
TI  - Repeated Colloidal Gold Tests in Rheumatoid Arthritis.

PMID- 18623822
TI  - Editorial.

PMID- 18623824
TI  - Morquio-Brailsford's Disease Simulating the Arthritic Manifestation of Rheumatoid
      Disease.

PMID- 18623823
TI  - Muscle Lesions in Rheumatoid Arthritis.

PMID- 18623825
TI  - Effect of Blood Transfusion on Rheumatoid Arthritis.

PMID- 18623826
TI  - Stimulation of the Suprarenal Glands in the Treatment of Rheumatoid Arthritis:
      Preliminary Report.

PMID- 18623827
TI  - Treatment of Rheumatoid Arthritis with ATP.

PMID- 18623828
TI  - The Neutral 17-Ketosteroids in Rheumatoid Arthritis and Spondylitis.

PMID- 18623829
TI  - Differential Sheep-Cell Agglutination Test in Rheumatoid Arthritis.

PMID- 18623830
TI  - Relation of the Adrenal Cortex to Rheumatic Disease: A Review of Some Recent
      Investigations.

PMID- 18623831
TI  - Pituitary Gland Implantations in Rheumatoid Arthritis.

PMID- 18623832
TI  - Investigations into Peripheral Circulatory and Metabolic Phenomena : On the
      "Reduction Time" of the Blood of the Skin and Its Relation to the Basal
      Metabolism of the Organism.

PMID- 18623833
TI  - Glycine in the Treatment of Gout.

PMID- 18623834
TI  - Rheumatic Polytendovaginitis.

PMID- 18623836
TI  - Fibrositis of Muscles.

PMID- 18623835
TI  - Tendon Lesions in Rheumatoid Arthritis.

PMID- 18623837
TI  - Editorial.

PMID- 18623838
TI  - IRON THERAPY IN THE ANAEMIA OF RHEUMATOID ARTHRITIS.

PMID- 18623839
TI  - Iron Therapy in the Anaemia of Rheumatoid Arthritis.

PMID- 18623840
TI  - Editorial.

PMID- 18623842
TI  - Editorial.

PMID- 18623841
TI  - Request for Reprints of Articles on Stress and the Adaptive Hormones.

PMID- 18623843
TI  - Editorial.

PMID- 18623845
TI  - Editorial.

PMID- 18623844
TI  - The Use of Colchicine in Gout.

PMID- 18623846
TI  - Treatment of Rheumatoid Arthritis by a Sanatorium Regime: The Black Notley
      Experiment.

PMID- 18623847
TI  - Differential Agglutination Titre (D.A.T.) in Juvenile Rheumatoid Arthritis.

PMID- 18623848
TI  - Comparison of Differential Agglutination Titre (D.A.T.) in Juvenile and Adult
      Rheumatoid Arthritis.

PMID- 18623849
TI  - Familial Incidence of Rheumatoid Arthritis.

PMID- 18623850
TI  - Differences between the Fever of Still's Disease and that of Rheumatic Fever.

PMID- 18623851
TI  - Evaluation of an Epidemiological Method: Rheumatoid Arthritis in Liberia.

PMID- 18623852
TI  - Erythrocyte Survival in Rheumatoid Arthritis.

PMID- 18623854
TI  - Empire Rheumatism Council: Twenty-Third Annual Report.

PMID- 18623853
TI  - On the Nature of the Rheumatoid Factor.

PMID- 18623855
TI  - Inactivation Test of the Lupus Erythematosus (L.E.) Plasma Factor.

PMID- 18623857
TI  - New Uricosuric Agent in the Treatment of Gout: para-Carboxybenzenesulpha
      diethylamide (Urelim).

PMID- 18623858
TI  - Spontaneous Atlanto-Axial Dislocation in Ankylosing Spondylitis and Rheumatoid
      Arthritis.

PMID- 18623856
TI  - The Experimental Production of Arthritis: A Review.

PMID- 18623859
TI  - Rheumatic Complaints in a Rural Population.

PMID- 18623860
TI  - Combined Aspirin and Cortisone Treatment of Acute Rheumatic Fever: A Controlled
      Trial in Young Men.

PMID- 18623861
TI  - Treatment of Rheumatoid Arthritis by Intramuscular Triamcinolone Acetonide and
      Triamcinolone Diacetate.

PMID- 18623862
TI  - Gold Therapy in Rheumatoid Arthritis: Final Report of a Multicentre Controlled
      Trial.

PMID- 18623863
TI  - Relation of Toxic Reactions in Gold Therapy to Improvement in Rheumatoid
      Arthritis: A Report.

PMID- 18623864
TI  - Heberden Oration, 1961: William Heberden.

PMID- 18623865
TI  - Femoral Head Destruction in Rheumatoid Arthritis and Osteo-Arthritis: A Clinical
      Review of 27 Cases.

PMID- 18623866
TI  - Observations on the Presence of Rheumatoid Serum Factor in Skin and Other
      Tissues.

PMID- 18623867
TI  - Gout, Steatorrhoea, and Megaloblastic Anaemia.

PMID- 18623868
TI  - An Immunofluorescence Study of Rheumatoid Factor.

PMID- 18623869
TI  - Clinical Studies on Behcet's Syndrome.

PMID- 18623870
TI  - RHEUMATOID FACTOR.

PMID- 18623871
TI  - Controlled Trial of the Effect of Complete Immobilization of the Joints in
      Rheumatoid Arthritis.

PMID- 18623872
TI  - Chondrocalcinosis Articularis: Section IV. Discussion.

PMID- 18623873
TI  - Chondrocalcinosis Articularis: Section V. Summary.

PMID- 18623874
TI  - Arthritis and Rheumatism Council for Research in Great Britain and the
      Commonwealth: TWENTY-SEVENTH ANNUAL REPORT.

PMID- 18623875
TI  - Inflammation.

PMID- 18623876
TI  - Kennedy institute.

PMID- 18623877
TI  - Opening address.

PMID- 18623878
TI  - Artificial Finger Joints in Rheumatoid Arthritis: I. DEVELOPMENT AND EXPERIMENTAL
      ASSESSMENT.

PMID- 18623879
TI  - Skeletal muscle involvement in systemic sclerosis.

PMID- 18623880
TI  - Behaviour of synovial fluid on articular cartilage.

PMID- 18623882
TI  - Introduction.

PMID- 18623881
TI  - The literature of rheumatism.

PMID- 18623883
TI  - Summing up.

PMID- 18623884
TI  - Editorial.

PMID- 18623885
TI  - The end of an era.

PMID- 18623886
TI  - Serum antigammaglobulins in juvenile rheumatoid arthritis.

PMID- 18623887
TI  - Brighton, 1971.

PMID- 18623888
TI  - The arthritis of Constantine IX.

PMID- 18623889
TI  - Treating HIV: when to start, who should treat, and still missing many.

PMID- 18623891
TI  - Acute retroviral syndrome: a challenge for primary care.

PMID- 18623890
TI  - UN sees progress inadequate on children and AIDS.

PMID- 18623892
TI  - Images in HIV/AIDS. Gastrointestinal malignancies in HIV/AIDS.

PMID- 18623893
TI  - Unusual case of Pneumocystis jiroveci pneumonia during primary HIV infection.
AB  - Symptomatic primary HIV infection occurs in an estimated 50% to 90% of patients.
      A constellation of symptoms that most closely resembles those of acute infectious
      mononucleosis characterizes the syndrome. On rare occasions, opportunistic
      infections present simultaneously with primary HIV infection. We describe a
      patient who presented with an episode of severe Pneumocystis jiroveci pneumonia
      during what appeared to be a prolonged primary HIV infection. Serological testing
      demonstrated the progressive development of reactive bands on serial Western blot
      determinations. This case highlights how primary HIV infection can produce
      profound immunosuppression through CD4 lymphocytopenia predisposing patients to
      opportunistic infection.

PMID- 18623894
TI  - Using the galactomannan assay in the diagnosis of invasive aspergillosis.

PMID- 18623895
TI  - Initial regimens for the treatment-naive patient: current understanding and
      practice.

PMID- 18623896
TI  - Coronary drug-eluting stents, thrombosis, and antiplatelet therapy: update and
      recommendations for the practicing pharmacist.

PMID- 18623897
TI  - Areas for improving care of type 1 diabetes: a role for pharmacists.

PMID- 18623898
TI  - Huntington's disease.

PMID- 18623899
TI  - Imatinib: new indication. New indications, but not robust evidence.
AB  - (1) Imatinib, a tyrosine kinase inhibitor, was first marketed for the treatment
      of chronic myeloid leukaemia and some gastrointestinal stromal tumours. Its
      indications have gradually expanded over the years. (2) There is no consensus
      treatment for adults with Philadelphia chromosome-positive acute lymphoblastic
      leukaemia. In a trial comparing imatinib versus chemotherapy as initial treatment
      for 55 patients, the haematological response rate was higher with imatinib. Non
      comparative trials provided haematological response rates of about 90%, but it is
      not known whether or not this translates into a survival advantage. In three non
      comparative trials including patients with relapsed or refractory disease after
      chemotherapy, 50% of patients showed a survival time of at least 7 months. In the
      absence of any direct comparisons, we do not know if this represents an
      improvement over the results obtained with the best palliative care. (3) The only
      potential cure for myelodysplastic syndromes is allogeneic haematopoietic stem
      cell transplantation but this is not always feasible. Some myelodysplastic
      syndromes are associated with myeloproliferation and PDGFR gene rearrangements;
      imatinib is the first drug available for these patients. The manufacturer has
      compiled data on 55 patients treated with imatinib. Most patients had a
      favourable haematological response, but no survival data were published. (4) The
      severity of the hypereosinophilic syndrome is highly variable. Forms associated
      with FIP1L1-PDGFRalpha gene rearrangements have a poor prognosis. Clinical
      evaluation of imatinib in this setting is based on a compilation of data
      concerning 176 treated patients. The haematological response rate was high in
      patients with the mutant gene, but it is not known whether this translated into
      increased survival. (5) Dermatofibrosarcoma protuberans is a rare form of mainly
      localised skin cancer. Treatment is based on surgical excision but relapses are
      frequent. In one series, 9 out of 12 patients treated with imatinib had at least
      a partial tumour response, making surgical excision possible in 3 cases. (6)
      Imatinib has diverse and frequent adverse effects; nausea and vomiting, oedema,
      fluid retention, cutaneous disorders and heart failure. There is some evidence
      pointing to a risk of urologic cancers and altered bone metabolism.

PMID- 18623900
TI  - Safe and efficient gene therapy--delivery makes all the difference.

PMID- 18623901
TI  - Reinvigorating the concept of benefit: the failure of drug company-sponsored
      research on human subjects.

PMID- 18623902
TI  - Killing cancer cells by targeting the EGF receptor.

PMID- 18623904
TI  - The future of privacy in a unified national health information infrastructure.

PMID- 18623903
TI  - PPM1H--new kid on the block.

PMID- 18623905
TI  - Whose cell line is it anyway? Intellectual property implications of New Jersey's
      policy on stem cell research.

PMID- 18623906
TI  - Pharmacist-provided medication therapy management (part 1): provider perspectives
      in 2007.
AB  - OBJECTIVES: To collect and describe information from providers of medication
      therapy management (MTM) services regarding (1) implementation strategies used
      for providing MTM services to patients/clients; (2) specific measures, if any,
      used to quantify the costs and benefits of MTM; (3) how the value of MTM services
      was tracked during 2007; and (4) barriers to offering MTM services to
      patients/clients. DESIGN: Descriptive, nonexperimental, cross-sectional study.
      SETTING: United States during 2007. PARTICIPANTS: Of the 6,873 providers who
      presumably received an e-mail invitation to participate in the survey, 687 (10%)
      responded and were included for analysis. INTERVENTIONS: Self-administered online
      survey. MAIN OUTCOME MEASURES: Implementation and monitoring of MTM. RESULTS: 65%
      of survey respondents were involved in providing MTM services as defined in the
      consensus definition used. Of these, 47% reported that they were contracted with
      programs to provide MTM services. Of respondents, 35% indicated that these
      contracts provided a positive return on investment (ROI), 31% reported that they
      did not provide a positive ROI, and 34% reported that they did not know.
      Providers varied widely on how they implemented MTM service offerings and
      typically did not use specific measures to quantify the costs and benefits of
      MTM. In addition, they did not use systematic methods for assessing value from
      providing MTM services to their patients. CONCLUSION: This descriptive
      environmental scan can serve as a baseline measure and be used for future
      comparisons.

PMID- 18623907
TI  - Meningococcal B vaccine: new drug. The only vaccine against some serogroup B
      meningococci.
AB  - (1) Invasive infections due to serogroup B meningococci can be life-threatening.
      Antibiotics are not always effective. Vaccines available in France do not protect
      against serogroup B meningococci. (2) In the French region of Normandy, a vaccine
      manufactured by the Norwegian National Institute of Public Health and directed
      against serogroup B meningococci. (2) In the French region of Normandy, a vaccine
      manufactured by the Norwegian National Institute of Public Health and directed
      against a meningococcal strain related to the strain circulating in this region
      has been used since summer 2006 to protect children over one year of age and
      adolescents. (3) A review of the 16 available immunogenicity studies shows that
      immunogenicity is similar in children and adults when the vaccine is administered
      in two doses, six weeks apart. The manufacturing process was modified in 1995,
      and the new vaccine could be less immunogenic: three doses provided results
      similar to those obtained with two doses of the older vaccine. This implies that,
      in epidemic situations, the maximum protection conferred by the vaccine would be
      reached 3 to 4 months after beginning vaccination. (4) A double-blind placebo
      controlled trial conducted between 1988 and 1991 included 171 800 adolescents
      aged 14 to 16 years who received two doses of the meningitis B vaccine, or
      placebo injections. During 29 months of follow-up, 12 invasive infections due to
      serogroup B meningococci occurred in the vaccine group, versus 24 cases in the
      placebo group. The protection rate was 57% but the confidence interval was very
      wide (21% to 78%). A correlation was established between the bactericidal
      antibody titre and clinical protection. (5) In this trial, the adverse events
      studied in 877 adolescents were infrequent: less than 4% of local adverse events,
      and about the same proportion of systemic adverse events (headache, nausea,
      fatigue, malaise), led to taking time off school. (6) Too few data are available
      for infants. And it is difficult to extrapolate to other countries the results
      obtained in Norway 10 years ago with a vaccine that was manufactured differently
      and may be more immunogenic. (7) In practice, vaccination with the Norwegian
      vaccine is justified in areas where an epidemic strain closely related to the
      vaccine strain is circulating, even though only about 60% of vaccinees are
      protected after three doses.

PMID- 18623908
TI  - Maraviroc: new drug. Multiple antiretroviral treatment failure: too soon to reach
      conclusions.
AB  - (1) The choice of treatment for HIV-infected patients in whom several lines of
      antiretroviral therapy have failed is particularly difficult. Some antiretroviral
      drugs (enfuvirtide and some HIV protease inhibitors) remain effective, at least
      in the short term. (2) Maraviroc is the first CCR5 antagonist to be licensed for
      use in this setting. It acts by blocking one of the two coreceptors, CCR5, needed
      for HIV entry into CD4+ lymphocytes. It is approved for use in HIV-infected
      patients with multiple antiretroviral failure. (3) Two double-blind placebo
      controlled trials including 1076 patients infected by HIV strains using only the
      CCR5 coreceptor tested the effect of adding maraviroc at a dose of 300 mg twice a
      day to an optimised treatment. After 8 weeks, maraviroc was more effective than
      placebo in reducing viral load (undetectable in 45.5% versus 16.7% of patients)
      and in increasing the CD4+ cell count (+124 cells/mm3 versus +61 cells/mm3); both
      of these differences are statistically significant. (4) After treatment with
      maraviroc, 50% to 60% of patients harboured viruses that did not exclusively rely
      on CCR5 for host cell entry. The possible clinical consequences of this change in
      tropism are unclear. (5) A double-blind trial of maraviroc included 190 patients
      with multiple antiretroviral failure who were infected by HIV variants not
      requiring CCR5 for host cell entry; maraviroc was not shown to be effective. (6)
      Data obtained with other CCR5 antagonists, and preclinical data obtained with
      maraviroc, point to a possible increase in the risk of hepatitis, infections,
      cancer, and QT prolongation. More data are also needed concerning the risk of
      muscle toxicity and ischaemic cardiovascular events. (7) Maraviroc is metabolised
      by the cytochrome P450 isoenzyme CYP 3A4, hence a high risk of interactions with
      CYP 3A4 inducers and inhibitors. (8) In practice, given the absence of long-term
      evaluation, clinical assessment of maraviroc is too limited to recommend the use
      of this drug outside the clinical trial setting.

PMID- 18623909
TI  - Carbamazepine oral syringe graduated in millilitres: New measuring device: risk
      of dosing errors.

PMID- 18623910
TI  - Parathyroid hormone: new drug. Osteoporosis: just a teriparatide me-too.
AB  - This recombinant parathyroid hormone has not been compared with bisphosphonates
      or with teriparatide. Its known safety profile is no more reassuring than that of
      teriparatide, and its administration is also inconvenient.

PMID- 18623911
TI  - Papillomavirus vaccine types 16 and 18: new drug. Cervical cancer: just another
      vaccine.
AB  - The papillomavirus 16, 18 vaccine, like the papillomavirus 6, 11, 16, 18 vaccine,
      reduces the risk of high-grade cervical dysplasia due to all viral genotypes by
      about 40% in young women who are not yet infected at the time of vaccination. The
      vaccine does not seem to provoke any serious adverse effects, but there is no
      proof that it reduces the risk of cancer.

PMID- 18623912
TI  - Fentanyl patch for stable chronic pain in children: new indication. Used fentanyl
      patches should be handled with care.
AB  - Fentanyl patch is an alternative for children who cannot tolerate morphine.
      Patches should be applied on the back of the upper body trunk.

PMID- 18623913
TI  - Risedronic acid and calcium + colecalciferol: new combination. A simple
      combination of two other products. A simple commercial ploy with no benefit for
      patients.

PMID- 18623914
TI  - Frovatriptan: new drug. Migraine attacks: an unnecessary triptan. Less effective
      than sumatriptan, but more adverse effects.

PMID- 18623915
TI  - [In praise of diversity: anthropology and aesthetics in Gautier's Mediterranean
      travels].

PMID- 18623916
TI  - [With silk against poverty: a chapter of Wurttemberg's social and development
      policy in the first half of the 19th century].

PMID- 18623917
TI  - The archaeology of the convict system in western Australia.

PMID- 18623918
TI  - Docetaxel: new indication. Metastatic gastric cancer: keep using fluorouracil
      based chemotherapy. No tangible progress.

PMID- 18623919
TI  - Meprobamate: still approved in France: labelling change. No role for meprobamate,
      in any indication. Safer options are available.

PMID- 18623920
TI  - You're the flight surgeon: pulmonary decompression sickness.

PMID- 18623921
TI  - Epidemiology of cancers of uterine cervix and corpus, breast and ovary in Israel
      and New York City.

PMID- 18623922
TI  - Influence of diphosphopyridine nucleotide (DPN) on photodynamic effects of low
      concentrations of methylene blue in ascites tumor cells.
AB  - When four thiazine dyes were added to ascites cell suspensions to yield 10(-4) M
      final concentration, the order of increasing effectiveness, for both stimulation
      of aerobic glycolysis in the dark and inhibition of aerobic glycolysis in the
      presence of added light, was thionine, methylene blue, thionine blue, and new
      methylene blue. After illumination, inhibition of anaerobic glycolysis occurred
      in the same respective dye order. Studies in depth of photodynamic effects of
      methylene blue on Ehrlich ascites cells revealed marked metabolic effects of
      light and 10(-4) M dye or lower. Diphosphopyridine nucleotide (DPN) with 5 X 10(
      6) M methylene blue and light almost completely abolished the Pasteur effect
      after only 10 minutes' illumination of the dye-cell-coenzyme system. The ability
      of light, methylene blue, and exogenous DPN to specifically inhibit the Pasteur
      effect is consistent with the view that DPN can be important to proper
      functioning of the Pasteur effect mechanism. It is suggested that perfusion with
      some of the less toxic photosensitive dyes in combination with conventional or
      lasered light may result in significant selective destruction of tumor cells in
      vivo.

PMID- 18623924
TI  - Mitotic delay and chromosomal aberrations induced by X rays in synchronized
      Chinese hamster cells in vitro.
AB  - Synchronized Chinese hamster cell populations in vitro were X-irradiated at
      different stages of the cell cycle and examined at the next metaphase. Mitotic
      delay varied according to the stage of the cell cycle at the time of irradiation.
      It was greatest for cells irradiated in middle to late S, moderate for cells
      irradiated in G2, and least for cells irradiated in G1. It increased
      approximately linearly with dose (0.7 hr./100 rad for S cells and 0.3 hr./100 rad
      for G1 cells). Chromosomal aberration rates also depended on the stage of the
      cell cycle at which the cells were irradiated. Chromatid aberrations were induced
      mostly during G2 and S (more in early S than late S), while chromosome
      aberrations were induced mainly in G1. Total breaks after 500 or 750 R showed a
      minimum frequency in late S and a maximum frequency in G2. This form of response
      correlates, but only in a general qualitative way, with the dependence of
      survival on cell cycle stage previously reported. Mitotic delay has a dependence
      on cell cycle stage quite different from either chromosomal aberrations or
      survival.

PMID- 18623923
TI  - Reactivity of human lymphocytes against autochthonous and allogeneic normal and
      tumor cells in vitro.
AB  - Human peripheral lymphocytes from tumor-bearing and non-tumor-bearing patients
      were added to monolayer cultures of autochthonous and allogeneic normal or
      neoplastic cells in vitro with or without phytohemagglutinin (PHA). The normal
      cells were derived from skin, the tumor cells from postnasal carcinomas or
      sarcomas. The cultures were scored for clearly visible plaques in the monolayer.
      Without PHA, lymphocytes affected autochthonous skin target cells in 1 of 16
      cultures. If PHA was added,the figure increased to nearly 50%(12/28). Whether
      this phenomenon is related to an autoimmune reaction or to some less specific
      effect of the PHA stimulus is unknown at present. In the absence of PHA,
      lymphocytes from African tumor-bearing hosts destroyed allogeneic skin
      fibroblasts in 4 of 14 cases, and lymphocytes from non-tumor-bearing Swedish
      donors showed this effect in 14 of 24 tests. The somewhat lower reactivity of the
      African lymphocytes was also apparent in other tests. It cannot be stated whether
      the difference was due to the tumor-bearing condition of the hosts or to some
      other differences involved in comparison of the two groups. Without PHA,
      lymphocytes of the African tumor patients destroyed their own autochthonous tumor
      cultures in 4 of 16 cases. Addition of PHA increased the proportion of positives
      to 20 of 28. A comparison with the corresponding figures for autochthonous skin
      cultures (1/16 and 12/28, respectively) indicates a relatively higher reactivity
      against the autochthonous tumor cells, both with and without PHA. This cannot be
      interpreted as a difference in target cell sensitivity to the same lymphocyte
      action, because no such difference was apparent when the sensitivity of skin and
      tumor to allogeneic lymphocytes was compared in the absence of PHA (4/14 and 4/14
      with African lymphocyte donors; 14/24 and 14/24 with Swedish lymphocyte donors,
      respectively). The most probable explanation is that the antigenic barrier
      responsible for the lymphocyte effect is larger for tumor than for skin, or that
      the results reflect a presensitization of the tumor donor against its
      autochthonous neoplastic cells.

PMID- 18623925
TI  - Serum haptoglobin type and cancer.
AB  - The distribution of haptoglobin types in 526 cancerous and 430 noncancerous
      subjects is presented. The frequency of haptoglobin 1 gene, in females, ranged
      sequentially from 0.264 in patients with cancer of the cervix, uterus, and ovary,
      through melanoma, breast cancer, cancer of the colon, to 0.467 in reticuloses.
      This was supported by statistically significant differences observed between some
      groups of cancer patients and normal controls. A different haptoglobin 1 gene
      frequency was found for male cancer patients.

PMID- 18623926
TI  - Hyperbaric oxygen and radiobiology of a C3H mouse mammary carcinoma.
AB  - A series of radiation dose-tumor control response assays was performed on the
      first-to-fourth generation isotransplants of a C3H/J mouse mammary carcinoma for
      radiation administered under four different conditions: hypoxia, a clamp across
      the root of the tumor-bearing part for 1 minute before treatment; air, animal
      respiring air at one atmosphere of pressure; O2 30 or 44 psi, animal respiring
      pure oxygen at 30 or 44 psi for 15 minutes before and during local tumor
      irradiation. When radiation was administered as a single dose (v = 1) to 250 mm3
      tumors, high pressure oxygen was only modestly effective in reducing the tumor
      control dose (TCD50); TCD50 hypoxia/O2 30 psi and TCD50 hypoxia/O2 44 psi were
      only 1.2 and 1.3, respectively. However, for similar treatment of 0.6 mm3 tumors
      and of even smaller "microcolonies," the ratios TCD50 hypoxia/O2 44 psi were 2.5
      and 3.2, respectively. These results are discussed with respect to simple tumor
      models so as to estimate the proportion of hypoxic cells present in tumors under
      normal conditions and the influence of oxygen breathed at increased pressure on
      that proportion. High pressure oxygen was found much more effective when combined
      with fractionated irradiation (v = 10) than with single-dose therapy. Thus TCD50
      hypoxia/O2 30 psi was 2.2 (v = 10) instead of 1.2 (v = 1). Finally, the ratio
      TCD50 hypoxia = 10/v = 1 was 2.15. These results are reviewed and inferences
      drawn as to the extent of tumor cell proliferation between treatments, repair of
      sublethal radiation injury by hypoxic cells, and the movement of cells from the
      hypoxic compartment to the aerobic compartment during fractionated irradiation (v
      = 10) under normal conditions.

PMID- 18623927
TI  - Studies on leukemia development in the SJL/J strain of mice.
AB  - Spontaneous reticulum cell neoplasms developed in 70-80% of intact male and
      female SJL/J mice at a mean age of 380 days. The neoplasms had a basic
      histological pattern of a multicellular type-B reticulum cell neoplasm, as
      designated by Dunn. The tumors were transplanted in isogenic mice. Serial
      passages of cell suspensions of these tumors were carried on through at least 4
      tumor-inducing generations, and the growing transplanted tumors maintained the
      structure of a reticulum cell neoplasm similar to the original tumor. A
      histological survey of spontaneous lesions in SJL/J mice revealed different
      characteristics of reticulum cell neoplasms, some similar to Hodgkin's lesions.
      Five or ten feedings of 7,12-dimethylbenz-[alpha]anthracene (DMBA) in
      polyethylene glycol 400 (1 mg DMBA per feeding) to SJL/J mice induced
      lymphosarcomas in 74-83% of the mice at a mean age of 157-188 days. A single
      feeding of DMBA induced lymphosarcomas in only 27% of the mice at a mean age of
      246 days. These DMBA-induced lymphatic leukemias do not appear to depend on the
      thymus for development--a 60% incidence of lymphosarcomas was obtained in adult
      thymectomized mice treated with DMBA, and 27% of the thymectomized DMBA-treated
      mice developed myeloid leukemia at a mean age of 180 days. Urethan was only
      slightly leukemogenic in SJL/J mice.

PMID- 18623928
TI  - Carcinogenesis from polymer implants: new aspects from chromosomal and
      transplantation studies during premalignancy.
AB  - Inbred CBA/H and CBA/H-T6 mice received implants of 15 X 22 mm plastic films.
      Plastic inserts and tissue capsules were cut in thirds at half monthly and
      monthly intervals. The first portion of the inserts and capsules was left in the
      original animal. The second portion was separated and individually transplanted
      into recipients that differed from the original animals with respect to the T6
      marker chromosome. The third portion and all tumors which developed in original
      and recipient animals were examined by karyological, histological, and cultural
      methods. Film pieces caused tumors in recipient animals up to 9 months after
      transfer, capsule tissue only up to about 1 month after transfer. Tumors in
      original and corresponding recipient animals were identical in their chromosomal
      stemlines and pace of premalignant maturation. The karyotype of the stemline was
      never discovered among the film-attached cell population because there seemed to
      be no cell division. This points to the existence of a single, specific
      premalignant cell clone residing on the film surface in a dormant state of
      nondivision many months before tumor appearance. At the end, the (pre)malignant
      cells detached from the film, invaded the capsule tissue, and propagated to
      produce the tumor within about 4 weeks. The existence of a specific inhibition
      phenomenon during the premalignant phase is suggested.

PMID- 18623929
TI  - Spontaneous interferon production in cultures of a cell line from a human
      myeloblastic leukemia.
AB  - Spontaneous and continuous production of an interference-inducing substance has
      been demonstrated in cultures of a cell line derived from a human myeloblastic
      leukemia. This substance had most of the characteristics of interferon.

PMID- 18623930
TI  - Production of interferon-like substances by human bone marrow tissues in vitro.
AB  - Three hundred and fifty-six bone marrow tissues obtained from patients of a
      general hospital were tested for spontaneous production after cultivation in
      vitro of interferon-like substances (ILS). Seventeen percent of the tissues
      produced ILS that protected human, but not chick, embryo cell cultures against
      the cytopathic effects of challenge virus infection. The incidence of ILS did not
      correlate with leukemia or other neoplastic diseases, or with any non-neoplastic
      disease.

PMID- 18623931
TI  - Neoplastic transformation of mouse and hamster cells in vitro with and without
      polyoma virus.
AB  - Several cell lines were examined under different culture conditions in an effort
      to find one that would not undergo "spontaneous" neoplastic transformation but
      could be transformed by polyoma virus. With such a cell line, large numbers of
      neoplastic and non-neoplastic cultures might be obtained for comparative studies.
      Four cell lines derived from different tissues of 2 strains of mice and all 8
      lines of cells from 5 different pools of hamster embryo cells underwent
      spontaneous neoplastic transformation without polyoma virus. However, certain of
      these lines might be useful, since neoplastic conversion occurred only after
      prolonged culture. Fairly reproducible neoplastic transformations could be
      induced by polyoma virus with high multiplicities of infection and rather drastic
      treatment of cells, including trypsinization. Although it has been postulated
      that normal Syrian hamster embryo cells have a finite lifespan in vitro, we found
      that under our culture conditions, continuously growing, non-neoplastic cell
      lines could be routinely established.

PMID- 18623932
TI  - Search for "indicators" of neoplastic conversion in vitro.
AB  - Certain responses of mouse and hamster cells to polyoma virus were examined with
      respect to their specificity as "indicators" of neoplastic conversion in vitro.
      These responses included the development of transplantation antigens and changes
      in morphologic growth pattern, cytology, karyology, rates of proliferation, and
      glycolytic activities. Under limited conditions, i.e., in short-term, slow
      growing cultures, the morphologic change in growth pattern and increases in
      glycolytic activity and proliferation rate induced by polyoma virus appeared to
      correlate with neoplastic conversion. However, in long-term or rapidly growing
      short-term cultures, similar morphologic patterns occurred in cells that
      subsequently tested as non-neoplastic. Also, such patterns could be induced by
      polyoma virus in cells already neoplastic. Cells that had undergone "spontaneous"
      neoplastic conversion frequently showed none of these morphologic features of
      virus-transformed cells. Prolonged culture of cells without added virus resulted
      in increased glycolytic activities and proliferation rates equivalent to those of
      virus-transformed cells. These changes occurred in at least one cell line long
      before evidence of neoplastic conversion. The cytologic changes in the virus
      treated neoplastic cells were similar to those usually associated with neoplastic
      cells in vivo and may possibly serve as sensitive indicators of in vitro
      neoplastic conversion. From the observations of this study, the change in
      morphologic growth pattern is interpreted not as loss of "contact inhibition,"
      but as a proliferative response accompanied by decreased adhesion of cells to the
      glass substrate.

PMID- 18623933
TI  - Magnetic susceptibility and electron spin resonance absorption spectra of mouse
      melanomas S91 and 591A.
AB  - A study of magnetic susceptibility and electron spin resonance (E.S.R.) spectra
      of Cloudman S91 and S91A melanomas and various mouse tissues was correlated with
      trace-metal analysis and known biochemical reactions. Average magnetic moments
      obtained from temperature-dependence studies showed the following order for
      tissues: S91>S91A>leg muscle. These results indicated a similar order in the
      relative concentration of magnetic species (free radicals and/or paramagnetic
      ions) and were confirmed by E.S.R. The E.S.R. spectra at different power levels
      showed that the free radical activity and the Cu2+ and Fe3+ activity attributed
      to different signals was generally higher in S91 than in S91A, which did not show
      an Fe3+ type signal. Normal tissues such as liver, spleen, heart, kidney, brain,
      and leg muscle showed varying amounts of free radical activity but not signals
      attributable to paramagnetic ions. E.S.R. spectra and trace-metal analysis at
      different stages of S91 tumor growth indicated a systematic increase in the free
      rad cal activity, total copper and iron concentrations, and paramagnetic ions,
      presumed to be Cu2+ and Fe3+. The S91A melanoma showed increase in total copper,
      but not in free radical and paramagnetic ion (CU2+) activity after the initial
      growth. Correlation of these findings with known biochemical reactions suggests
      that the free radical activity may be attributed partly to melanin and
      intermediates of various enzymatic reactions. Presumed paramagnetic ion activity
      cannot yet be ascribed to specific biostates.

PMID- 18623934
TI  - Virus containing lymphocyte cultures from cancer patients.
AB  - Seven continuous cell cultures were established from 45 lymphoid tissue specimens
      from 43 cancer patients. All cultures were free-floating and appeared to be
      primarily lymphoblasts. Electron microscopic examination revealed herpesvirus
      like particles in all the established cell lines and in one cell line that was
      maintained for only 1 month. The particles appeared identical to those observed
      in Burkitt's lymphoma and other lymphoma and leukemia cultures. In one instance
      virus particles were observed in the original tissue specimen before cultivation.
      The virus particles were not infectious for several cell lines known to be
      susceptible to herpes simplex virus and other members of this group.

PMID- 18623935
TI  - Ultrastructural analysis of the early development of teratocarcinomas.
AB  - Genital ridges of 12-day embryos of strain 129 mice were transplanted into the
      testes of adult mice of the same strain. Of the transplants that differentiated
      into fetal testes, 80% contained intratubular teratocarcinomas by the 7th day
      after transplantation. These teratocarcinomas were studied ultrastructurally,
      daily from the 7th-14th day following transplantation, to gain information about
      the histogenesis of the tumors and the mode of development of multipotent cells.
      The embryonal carcinoma cells, which are the stem cells of teratocarcinomas, so
      closely resembled primordial germ cells that the former appeared to be derived
      from the latter. The cytoplasm of these multipotential cells was characterized by
      large numbers of dispersed ribosomes and polysomes with few membranous organelles
      other than mitochondria. Among the earliest signs of differentiation was the
      development of rough-surfaced endoplasmic reticulum and Golgi complexes, followed
      by modification of the plasma membrane.

PMID- 18623936
TI  - Lysosomal changes in lytic and nonlytic infections with the simian vacuolating
      virus (SV40).
AB  - Lysosomal changes have been observed by histochemical methods in the BSC-1 green
      monkey kidney cell line and the 3T3 mouse cell line infected with high
      multiplicities of simian vacuolating virus (SV40) and in 3T3 cells infected with
      herpes simplex virus. BSC-1 cells infected with SV40 showed marked cytoplasmic
      vacuolation and lysis. The lysosomes were enlarged and aggregated and there was
      second-stage activation with release of enzyme into the cytoplasm. Possibly, some
      product of viral replication in the nucleus is released into the cytoplasm and
      brings about changes in lysosomes and other cytoplasmic organelles. Lysosomal
      enzymes probably contribute to the dissolution of cells and release of virus from
      nuclei. 3T3 cells infected with SV40 under these conditions do not lyse, but a
      large proportion may become transformed. First-stage activation of lysosomes was
      seen for at least 6 days. After 6 days these changes disappeared. The possible
      relationship of lysosomal changes to the events occurring in transformed cells is
      discussed. The cells infected with herpes simplex virus showed marked cytopathic
      effects associated with second-stage lysosomal activation.

PMID- 18623937
TI  - Experimental carcinogenesis of the lung. II. Influence of phenols in the
      production of carcinoma.
AB  - The acidic Fractions (including phenols) were separated from two somewhat
      different coal tars. Various blends and an original tar produced aerosols to
      which 5 groups of male C3H/HeJ mice were exposed 2 hours, 3 times weekly, for 55
      weeks. Animals were killed at intervals. The lungs and tracheas of all mice were
      examined grossly and microscopically for neoplasms or relevant morphologic
      changes. After 46 weeks, 32 survivors in groups 2 and 4, which received similar
      aerosols containing phenols, had 4 incidences of adenocarcinoma, 19 of
      intrabronchial adenoma, and 10 of squamous metaplasia. In 20 survivors of group
      3, which received the same far without phenols, there was no incidence of
      adenocarcinoma, 11 had intrabronchial adenoma and 2 had squamous metaplasia.

PMID- 18623938
TI  - Changes in 3H-thymidine incorporation into the DNA by histones from normal and
      tumor tissues.
AB  - Attempts were made to isolate a factor from tumor tissue which, after injection,
      enhances the 3H-thymidine incorporation into the DNA of mice. This factor was in
      the cell nuclei and was extractable together with acid-soluble nuclear proteins
      (histones). Additional purification showed that this factor was either closely
      bound with the very lysine-rich histone (F1), or it was this histone itself. Acid
      soluble nuclear proteins prepared from liver and thymus did not influence the
      incorporation of 3H-thymidine into DNA after injection. The very lysine-rich
      histone (F1) in these extracts was in an inactive form. It could be activated by
      separation from other acid-soluble nuclear proteins. Purified, the very lysine
      rich histone (F1) enhanced the 3H-thymidine incorporation into DNA, regardless of
      its being prepared from tumor or nontumor tissues. By enhancing the incorporation
      of 3H-thymidine into DNA after injection, the very lysine-rich histone (F1)
      significantly differed from arginine-rich (F2aF3) and lysine-rich (F2b) histones
      which suppressed the 3H-thymidine incorporation.

PMID- 18623939
TI  - Clinical classification of extent of disease in cancer of the breast.
AB  - A series of 2,039 cases of breast cancer in women under 65 years of age was used
      for an empirical-statistical approach to the classification of extent of disease.
      Comparisons were made with the staging recommendations of an American and an
      international committee. The uses for such classification schemes by the
      clinician in assessing prognosis and deciding on a treatment plan are considered.
      It is suggested that the same treatment plan is not necessarily appropriate for
      all patients falling into the same prognostic class, because there is marked
      variation in the clinical characteristics of patients within a class.

PMID- 18623940
TI  - High resolution autoradiographic study of normal lactating mammary gland and
      mammary tumors of the mouse: preliminary report.
AB  - Protein metabolism of normal lactating gland and mammary tumor cells was studied
      with high resolution autoradiography. Special attention was devoted to the Golgi
      zone in both cell types because of the involvement of this structure in milk
      protein secretion in the normal gland cell and the topographical relation of this
      apparatus with viral "inclusion bodies" in the tumor. In the normal gland, the
      cycle of protein secretion was completed in about 50 minutes, the main part of
      the cycle being represented by a heavy and extensive labeling of the Golgi zone.
      In the tumorous gland, marking was relatively stationary and remained within the
      cell, the label predominating in the ergastoplasm with only a faint labeling of
      the Golgi apparatus. Percent markins of the nucleus was notably greater in the
      tumor cell as opposed to the normal gland cell. In the calculation of the
      specific activities of the tissues, the size of the nucleus of both cell types
      was very similar, while the cytoplasm of the normal gland was five times that of
      the tumor cell. Comparison of the specific activities showed that the over-all
      activity of the two cell types was not significantly different. This phenomenon
      supports a theory proposed by Schultze whereby the ratio of protein incorporation
      into the nucleus and the cytoplasm is constant and the value of this ratio
      decreases as the metabolic activity of the cell increases.

PMID- 18623941
TI  - Aging and cancerogenesis. IV. Interrelationships among age, immune response, and
      tumor incidence in several strains of mice.
AB  - Immune reactivity of mice with various incidences of spontaneous tumors was
      measured at different points in their lifespan. Cytotoxic activity of immune sera
      from 3- and 12-month-old mice was high or moderately high in AKR/J, SJL/J, and
      A/HeJ mice in which high incidences of spontaneous tumors occur by the 12th
      month, and in SWR/J and C3HeB/-FeJ mice in which high incidences of spontaneous
      tumors reportedly occur after 18 months of age. A decrease in primary antibody
      response accompanied old age in 4 of the 6 strains tested (including randombred
      Swiss ICR/Ha), but not in AKR/J or A/HeJ mice. These facts, together with
      previous tests of cellular response in these mice, imply that under these
      experimental conditions little correspondence exists between humoral and cellular
      response. Further, host immunity may be only secondarily implicated in neoplastic
      formation.

PMID- 18623942
TI  - Infection of an established mouse cell line with cell-free Rauscher leukemia
      virus. I. Cytological study with the electron microscope.
AB  - Infecting mouse bone marrow cells (JLS-V9) with cell-free Rauscher leukemia virus
      demonstrated that monolayers of JLS-V9 cells were susceptible to infection with
      both cell-free plasma and tissue-culture-propagated Rauscher virus. The infected
      cultures maintained the continuous release of the virus. Cells and concentrated
      supernatant fluids from infected cells were periodically examined under the
      electron microscope by thin sectioning and negative staining techniques after
      inoculation with either mouse plasma or tissue-culture-propagated virus. After
      adsorption the virus underwent a prolonged eclipse or latent period. Virus
      budding was initially detected about 10 days after primary infection. These
      observations were further confirmed by the simultaneous appearance of
      extracellular virus. The budding process was followed by accelerated virus
      multiplication which reached maximum production 2-3 weeks later. Before the onset
      of budding no significant morphologic changes were seen in the infected cells.

PMID- 18623943
TI  - Survival of mice bearing a transplanted syngeneic lymphoma following treatment
      with cyclophosphamide, 5-fluorouracil, or 1,3-bis(2-chloroethyl)-1-nitrosourea.
AB  - SUMMARY-A model has been derived for the effect of the chemotherapeutic agents
      cyclophosphamide (CY), 5-fluorouracil (5-FU), and 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU) on the survival of mice bearing a transplantable lymphoma. The
      model is based on assumptions that 1) failures in treatment result from the
      survival of viable malignant cells, 2) the lymphoma cells in the host increase
      exponentially with time, 3) the host dies when the lymphoma cell population
      reaches a critical value, and 4) the number of lymphoma cells in the host
      decreases exponentially as a function of the infected drug dose. Parameters were
      found for the growth of lymphoma cells in vivo and for the survival of lymphoma
      cells in the host following the administration of CY, 5-FU, and BCNU. When these
      parameters were incorporated into the model, predictions were obtained concerning
      the survival time of lymphoma-bearing mice as well as the fraction of long-term
      survivors as a function of the injected dose. It was found that the model and
      experimental data were in excellent agreement for low doses of the drug, i.e.,
      doses which reduced the survival of the lymphoma cell population to the order of
      10(-4) survival. However, discrepancies were observed above these dose levels.
      The discrepancies are discussed in terms of the assumptions of the model.

PMID- 18623944
TI  - Studies on Marek's disease. I. Experimental transmission.
AB  - A strain of infectious agent, HPRS-B14, was isolated from a case of Marek's
      disease and maintained through 40 serial passages. This agent produced a disease
      characterized by neural involvement and, in some affected chickens, lymphoid
      tumors principally involving the ovary. This disease conformed to the description
      of the classical form of Marek's disease. This disease is contagious, spreading
      to chickens by direct and indirect contact with infected chickens. Females were
      more susceptible to the disease than males. Treatment with female and male sex
      hormones had no significant effect on the incidence of Marek's disease. Lines of
      chicken also differed in their susceptibility to disease produced by the HPRS-B14
      agent, and it is concluded that these differences are due to the genetic
      constitution of the chicken. Chickens of a susceptible line inoculated with HPRS
      B14 at 50 days of age were more resistant to the development of Marek's disease
      than chicks of the same line inoculated at 1 day of age. Blood and other organs
      and tissues of chickens, clinically affected with Marek's disease produced by
      HPRS-B14, were infective. Infectivity was associated with cell-containing
      fractions of blood and kidney tissue. It is concluded that infectivity of blood
      and other organs is due to an infectious agent, but we have insufficient evidence
      at present to classify the HPRS-B14 agent of Marek's disease.

PMID- 18623945
TI  - Studies on Marek's disease. II. Pathogenesis.
AB  - The development of Marek's disease (fowl paralysis; neurolymphomatosis) has been
      studied by examination of peripheral nerves and other tissues at different times
      after infection of young chicks with the HPRS-B14 strain of Marek's disease.
      Three types of nerve lesions were found: 1) A-type, characterized by
      proliferation of lymphoid cells, presence of Marek's disease cells, and sometimes
      demyelination and Schwann cell proliferation; 2) B-type, characterized by diffuse
      infiltration by plasma cells and mainly small lymphocytes, usually interneuritic
      edema, sometimes demyelination and Schwann cell proliferation; 3) C-type,
      characterized by light infiltration by plasma cells and small lymphocytes. A
      mixed A- and B-type lesion was also found. Serial killing experiments and
      grouping of lesions from transmission experiments according to the time elapsed
      since infection indicate that the nerve lesion follows the progression: A-type-->
      mixed A- and B-type-->B-type. The C-type lesion is believed to be a mild form of
      the B-type. The study indicates that Marek's disease is characterized by a
      neoplastic-like proliferation of lymphoid cells in the nerves and in other
      organs, notably the ovary. In some birds the proliferation is progressive and
      they succumb early in the course of the disease with tumor-like infiltration of
      the nerves and often other organs. Demyelination and other nerve tissue changes
      appear to be secondary to the lymphoid proliferation. In other birds the
      proliferation of lymphoid cells in the nerves is arrested, and the lesion changes
      into one of a more inflammatory appearance.

PMID- 18623946
TI  - Neoplasms occurring in aged Fischer rats, with special reference to testicular,
      uterine, and thyroid tumors.
AB  - Inbred Fischer rats were set aside as nonbreeders specifically to obtain tumors
      of endocrine organs and endocrine-responsive tissues that might be used in
      studies of hormone responsivity. The average age at death or autopsy was 675 days
      for 102 females, and 725 days for 92 males. The tumor data are recorded for those
      animals that were autopsied (91%). Sixty-eight percent of the males developed
      testicular interstitial (Leydig) cell tumors and in three fourths these were
      bilateral. One half of the 20 tumors transplanted into isologous hosts grew to a
      palpable size. In all instances where growth occurred it was more rapid in
      castrate than in intact male recipients. At least four of these transplanted
      tumors produced androgen. Twenty-one percent of the females had macroscopically
      evident uterine polypoid tumors that were endometrial in origin. Nine of these
      were transplanted into isologous hosts; 4 grew as sarcomas and 5 maintained their
      original benign, polyp-like microscopic appearance. Three of these latter tumors
      grew more rapidly in intact females than in intact males or castrate hosts of
      either sex. Nine of the aged rats developed grossly evident tumors of the thyroid
      that morphologically were typical type-gamma nodules. A papillary adenocarcinoma
      was found in the contralateral lobe of the thyroid of 1 of these rats. Only 1
      type-gamma nodule was transplanted, and after 1 year it has grown to
      approximately 1 cm in diameter in 1 of the 2 untreated male recipients. The
      incidence of breast, adrenal medullary, and pituitary tumors, as well as of other
      miscellaneous tumors, was not notably different from that reported by several
      investigators observing aged rats of different genetic background.

PMID- 18623947
TI  - Morphologic responses to a murine erythroblastosis virus.
AB  - A recently described mouse erythroblastosis virus (MEV) was passed to newborn
      W/Fu rats. The rats developed generalized malignant lymphomas after 6-7 months.
      Two separate serial cell-free passage series were initiated. Rat lymphomas
      induced erythroblastosis in less than 20% of the rats that died within 4 weeks
      after inoculation. The surviving rats remained apparently healthy for months
      until they died from lymphomas. Inoculation of newborn C3Hf/Gs mice with the same
      Filtrates caused only lymphomas in 35-50% of the mice after 3-8 months. The
      lymphomas were morphologically indistinguishable from thymic lymphomas induced in
      mice and rats by Gross' leukemia virus. A different morphologic response was
      observed by serial passages of spleen filtrates or plasma from rats with
      erythroblastosis. All rats died within 4 weeks with erythroblastosis. In
      addition, multiple sarcomas and polyostotic osteolytic lesions were found in most
      rats of such erythroblastosis passages. The same rat erythroblastosis filtrates
      induced erythroblastosis and sarcomas but no osteolytic lesions in C3Hf/Gs mice.
      Erythroblastosis in rats was similar to the disease previously described in mice,
      except for a marked normoblastosis and cerebral hemorrhages which did not occur
      in erythroblastotic mice. The sarcomas arose in multiple sites and were
      histologically undifferentiated. The osteolytic lesions were likewise
      multicentric in origin, affecting particularly the vertebrae and long bones.
      Their exact nature could not be determined.

PMID- 18623948
TI  - Trace-metal requirements of NCTC clone 929 strain L cells.
AB  - The effects of iron, zinc, copper, manganese, and Methocel on the growth of L
      cells in a synthetic medium were studied. The medium was iron-deficient unless a
      supplement of 1.0 g/liter Methocel HG (4,000 centipoises), Methocel ash
      equivalent to 1.0 g/liter Methocel, or 1.0 microM FeSO4 was added. Cells grew
      faster in the presence of FeSO4 or Methocel ash (generation time = 40 hours) than
      of Methocel (generation time = 110 hours), but Methocel was needed to protect
      cells from mechanical destruction. Treating the growth medium with Dowex A-1
      chelating resin produced a medium deficient in both iron and zinc. The iron
      requirement in this medium varied between 0.6 and 1.4 microM, depending on the
      concentrations of other cations added to the medium. A copper concentration of at
      least 0.4 microM was beneficial as it reduced the amount of iron necessary for
      cell growth. No manganese was required in this medium; any added manganese
      produced an inhibition of cell growth. Additional iron could reverse this
      inhibition. The minimum iron requirement for the production of L cells was 3
      nmoles/mg cell nitrogen produced. Approximately 0.6 microM zinc was required for
      maximum cell growth in resin-treated medium.

PMID- 18623949
TI  - Effect of ovariectomy at different ages on development of mammary tumors in (C3H
      x R3)F1 mice.
AB  - The rate of development of mammary tumors in (C3H X RIII)F1 hybrid mice
      ovariectomized at 2 months of age was similar to that of mice ovariectomized at 3
      months. The increased rate of tumor development in many females ovariectomized at
      4 or 5 months over that of females ovariectomized at 2 or 3 months indicates that
      the ovaries before their removal affected the subsequent development of mammary
      tumors. In the controls, the mean tumor age was much lower and the tumor
      incidence higher than in the ovariectomized females. Nodular hyperplasia of the
      adrenals was present in all tumor-bearing mice spayed at 2 or 3 months of age and
      in many of those spayed at 4 or 5 months. These findings, with the use of F1
      hybrids of C3H female X RIII hermaphrodite, agree with the postulate that
      hyperplastic adrenals of spayed mice of the C3H strain secrete estrogenic
      substances capable of inducing mammary tumors.

PMID- 18623950
TI  - Tumor induction in germfree rats with methylazoxymethanol (MAM) and synthetic MAM
      acetate.
AB  - The glucoside cycasin, an effective hepatotoxin and carcinogen in conventional
      rats, fails to produce these effects when administered to germfree rats. The
      hepatotoxic and carcinogenic effects of cycasin can also be elicited after prior
      hydrolysis to the aglycone. The aglycone (MAM) and the synthetic aglycone acetate
      ester produce all the effects in germfree rats of which the intact glucoside is
      capable only when fed to conventional rats. The aglycone is therefore the
      proximate carcinogen. Its liberation from the glucoside in conventional rats is
      mediated in the intestinal tract by a beta-glucosidase of bacterial origin.
      Intraperitoneal administration of the synthetic aglycone acetate and the free
      aglycone appears to be the most effective route for tumor induction and, of these
      resulting tumors, the most frequent are in the intestinal tract.

PMID- 18623951
TI  - Pain management practices with older adults on acute medical units.
AB  - Persistent pain is a significant problem for older hospitalized adults and their
      health care team. A better understanding of the approach to pain management in
      the clinical setting will provide guidance for the development of improvements in
      clinical management. The purpose of this study was to determine the prevalence of
      pain and to examine the current state of pain assessment and management in older
      adults on the six acute medical units of an academic health sciences centre.
      Findings revealed that 70% of older patients were in pain, nurses had limited
      awareness of their patients' pain, documentation of pain assessment and
      management was lacking, and pain was under-treated. Utilization of practice
      guidelines related to management of persistent pain in older adults in acute care
      settings is recommended, and an approach to their implementation, including
      identifying and overcoming the barriers to such best practices, is warranted.

PMID- 18623952
TI  - Quality improvement best practices and long-term indwelling urinary catheters.

PMID- 18623953
TI  - Climate change. Polar express.

PMID- 18623955
TI  - Energy. Roping the Sun.

PMID- 18623954
TI  - Microbiology. Bring in the noise.

PMID- 18623956
TI  - Genetics. Ancient gene, new tricks.

PMID- 18623957
TI  - Conservation. Saving kermit.

PMID- 18623958
TI  - Life in old lava.

PMID- 18623959
TI  - A bug's sex life. Interview by Charles Q Chou.

PMID- 18623960
TI  - Private, historical and genetic truths.

PMID- 18623962
TI  - Sacred science. Can emergence break the spell of reductionism and put
      spirituality back into nature?

PMID- 18623961
TI  - A deadline on malaria.

PMID- 18623963
TI  - The self-organizing quantum universe.

PMID- 18623964
TI  - New jobs for ancient chaperones.

PMID- 18623965
TI  - Traces of a distant past.

PMID- 18623966
TI  - Hands-on computing.

PMID- 18623967
TI  - No-till: the quiet revolution.

PMID- 18623968
TI  - The neuroscience of dance.

PMID- 18623969
TI  - Simple groups at play.

PMID- 18623971
TI  - Nimble skyscrapers at sea.

PMID- 18623970
TI  - Going with his gut bacteria.

PMID- 18623972
TI  - How does food's appearance or smell influence the way it tastes?

PMID- 18623973
TI  - From strength to strength!

PMID- 18623974
TI  - Root canal shaping using rotary nickel-titanium files in preclinical teaching.
AB  - AIMS: This study set out to evaluate the prevalence of iatrogenic events during
      preclinical teaching of endodontics, comparing manual stainless steel versus
      nickel-titanium (Ni-Ti) rotary techniques for shaping natural root canals.
      METHOD: Two groups of 13 inexperienced dental students were randomly made up and
      asked to shape 104 canals in natural teeth. Group R used Ni-Ti rotary files for
      shaping while Group M used a sequence of five manual stainless steel files.
      Occurrence of file breakage, loss of work length, and iatrogenic instrumentation
      on apical foramina were evaluated. RESULTS: Overall occurrence of adverse events
      during shaping did not differ between the groups, being 58% in Group R and 51% in
      Group M. Inter-group distribution of type of event differed significantly,
      however. File breakage (7.7%) and loss of working length of > 2 mm (6.7%)
      occurred only in Group R. Iatrogenic shaping on apical foramina showed the same
      frequency in each group. CONCLUSION: Manual instrumentation is safer than rotary
      instrumentation in the hands of inexperienced students. Acquiring skill in the
      use of Ni-Ti rotary instrumentation requires specific preclinical training to
      avert file breakage. These findings argue for the rethinking of theoretical and
      practical coursework in endodontics teaching, especially in dentistry schools
      where students are required to treat patients during their training.

PMID- 18623975
TI  - [Cranio-cervical posture and hyoid-mandibular-pharyngeal equilibrium in the
      presence of factors related to respiratory dysfunction].
AB  - AIM: The goal of this study is to know the modifications of the cranio-cervical
      posture which accompany the functional anomalies by the nasal breathe of black
      African children. MATERIAL AND METHOD: The study consists of a cephalometric
      comparison. Sixteen parameters measured on cephalograms of 98 schoolboys from 6
      to 15 years were used. The children were divided into two groups according to
      their usual mode of breathing: 50 mouth-breathing children and 48 nasal
      breathers. The mode of breathing used three clinical tests: the mirror test,
      Rosenthal test and nasal reflex. RESULTS: The results show a significant
      difference of slope the cervical column between the two groups of children (t
      student). The oral breathers have the rhinopharyngeal airway dimensions more
      narrowed. The hyoid bone is more distant of the epiglottis and the mandible is
      more divergent. However, factor analysis of cephalometric variables suggested
      that craniocervical angulation (C2C4/SN) is independent of the other variables in
      oral breathers. Its dependence with is clear in nasal breathers. CONCLUSION: The
      children with predominantly mouth breathing exhibent a cranio-cervical
      hyperextension which could not closely be associated hyo-mandibulo-pharyngeal
      equilibrium.

PMID- 18623976
TI  - [Prevalence of oro-dental injuries in wrestling in Senegal].
AB  - Wrestling is a sport that is deeply-rooted in Senegalese cultural values. It is a
      popular sport that comes from local traditions but that has been influenced by
      boxing. This influence has made wrestling evolve to include the practice of
      boxing without gloves. Howeve, this practice causes many traumas in the mouth and
      teeth. The general objective of this study is to determine the frequency of the
      traumas among wrestlers who practice this form of wrestling associated with
      boxing. The specific objectives are to appreciate the bucco-dental conditions of
      the wrestlers, to evaluate the frequency and nature of the traumas in the
      intention to make recommendations and offer perspectives. 63.2% of wrestlers have
      at least presented a buckle or dental trauma. 28.8% of bucco-dental traumas occur
      among young wrestlers between 25 and 30 years and, 22.4% relate to the group
      between 19 and 24 years. 24.8% of bucco-dental traumas occur among wrestlers of
      the first category, followed by these of the second category with 21.6%, the
      fourth category with the lowest rate, 4% being last. It has been noted that 60%
      of buck-dental traumas occur in championship matches. 77.2% of dental and bucco
      traumas affect the upper jaw while. 22.8% affect the lower jaw. Affect teeth are
      often the group incisivo-canin. The National committee for the Management of
      wrestling in Senegal should make mandation the wearing of adapted gloves to
      attenuate the impact of blows. The Committee could also ban the inclusion of
      boxing practices in traditional wrestling and make compulsory the wearing of
      teeth protect in devices to minimize cases of bucco-dental traumas.

PMID- 18623978
TI  - Assessment of oral status and oro-pharyngeal candidosis in elderly in short-term
      hospital care.
AB  - OBJECTIVES: To evaluate prevalence of oral candidosis and predisposing conditions
      in hospitalized elderly patients. DESIGN: We examined 104 elder patients recently
      hospitalized in two geriatric hospitals for shortterm hospital care. METHODS:
      Information was collected on patients' sex, age, mental and physical
      disabilities, smoking habits, medical prescriptions, oral pathologies, denture
      wearing, oral hygiene habits and oral hygiene level. Quality of existing dentures
      was evaluated. Oral mucosae were examined for clinical signs suggesting oral
      candidosis. Semiquantitative cultures of Candida were carried out to confirm the
      clinical diagnosis. RESULTS: The diagnosis of oral candidosis was confirmed in
      18/54 patients showing clinical signs of oral candidosis. Confirmed oral
      candidosis was associated with the presence of other infections, proteo-caloric
      denutrition, ongoing antibiotic therapy, and denture wearing. Dentures in
      patients with confirmed oral candidosis at poorer technical quality of the
      acrylic surface in contact with the underlying mucosa. CONCLUSION: The wearing of
      removable dentures is a major predisposing factor for oro-pharyngeal candidosis
      of elderly patients in short-term hospital care. Appropriate oral and denture
      hygiene measures as well as denture wearing habits should be introduced or
      maintained to prevent this infection.

PMID- 18623977
TI  - [Periodontal status in a sample of Senegalese women using hormonal
      contraception].
AB  - Hormonal contraception is based on the use of synthetic hormones containing
      variable doses of oestrogen and progesterone making it possible to avoid
      pregnancy in a temporary and reversible way. The objective of this study is to
      evaluate the periodontal status of a sample of Senegalese women under hormonal
      contraceptive. One hundred women using contraception since at least 6 month were
      paired on the age, the socio-economic profile and oral hygiene with a control
      group. Oral hygiene (plaque index (PI) of Silness and Loe), the inflammation
      (gingival index (GI) of Loe and Silness), probing depth and clinical attachment
      loss were recorded. With equal hygiene, the scores of the gingival index were
      significantly higher among women under contraceptive (p < 0.001). Inflammation
      was significantly more marked for the women who used contraception in injectable
      form compared to the control group (p < 0.001). Probing depth (3.01 +/- 0.04) and
      clinical attachment loss (3.19 +/- 0.08) were significantly more important among
      women under contraceptive (p < 0.001). The women under contraceptive seem to set
      up a group at risk for developing a periodontal disease, it is thus necessary to
      systematise periodontal appraisal before and during contraceptive use period.

PMID- 18623979
TI  - Bone alterations during HIV infection.
AB  - Osteopenia and osteoporosis are common in HIV-1-infected individuals and
      represent a challenge in clinical and therapeutic management. Since the
      mechanisms underlying this degenerative process are largely unsettled and it has
      not yet been determined whether bone dysfunction is linked to HIV-1-mediated
      direct and/or indirect effects on osteoblasts/osteoclasts cross-talk regulation,
      this brief review analyzes an array of mechanisms that could account for the
      dramatic bone derangement (bone loss and osteopenia/osteoporosis) during the
      course of HIV-1 infection.

PMID- 18623980
TI  - Risk management of febrile respiratory illness in emergency departments.
AB  - Febrile Respiratory Illness (FRI) is defined as a new or worsening episode of
      either cough or shortness of breath, presenting with fever (temperature 38
      degrees C or higher) or chills in the previous 24 hours. Some FRI could cause
      large outbreaks of potentially life-threatening diseases (multi- or extensively
      drug resistant MTB, SARS, pandemic influenza) if not adequately controlled.
      Emergency Departments (EDs) are preferential sites of disease transmission
      because of the presence of both infectious and susceptible patients in the same
      space, the lack of rapid isolation of infectious patients, and the frequent and
      close contacts among patients and HCWs often not protected by PPE. The management
      of risk of FRI transmission is thus extremely important in EDs, where all
      procedures of infection control should be in place and continually monitored and
      assessed. In this article the main procedures for the management of risk of FRI
      transmission in EDs are described and discussed.

PMID- 18623981
TI  - Non-organ-specific autoantibodies in renal transplant recipients: relation to BK
      virus infection.
AB  - Polyomavirus BK reactivation is common in renal transplant recipients and may
      cause nephropathy with significant graft dysfunction. The induction of anti
      double stranded DNA (anti-dsDNA) antibodies by BKV has been described in
      experimental animals and during primary infection, and has been implicated in the
      pathogenesis of systemic lupus erythematosus. This study evaluated the occurrence
      of anti-dsDNA antibodies and non-organ-specific autoantibodies (NOSA) by indirect
      immunofluorescence before transplantation and at 3 and 6 months post
      transplantation in 90 renal transplant recipients and the association with BKV
      reactivation, demographic and clinical features. Moreover, the relation to HCMV
      infection, as detected by pp65-antigenemia, was also evaluated. Post
      transplantation NOSAs were present in 23/90 (25.6%) and anti-dsDNA antibodies in
      17/90 (18.9%). BK viremia was detected in at least one serum sample in 22
      patients: 9 anti-dsDNA antibody-positive vs 13 negative (p<0.01). No significant
      correlation between the occurrence of NOSAs and anti-dsDNA antibodies and
      demographic and clinical features was found. No significant association with pp65
      antigenemia-positivity was found, although antigenemia was positive in 6/23 NOSA
      positive patients (26.1%). Although a relation seems to exist between BKV and the
      occurrence of anti-dsDNA antibodies in renal transplant patients, the lack of
      correlation with other epidemiological and clinical features does not allow any
      conclusion. The role of autoimmune response in this context and the relation with
      other patient-related factors and infectious agents should be further
      investigated.

PMID- 18623982
TI  - Rapid and accurate quantification of different HCV genotypes by LightCycler Real
      Time PCR and direct sequencing of HCV amplicons.
AB  - Follow-up of chronically infected HCV patients is the primary clinical goal in
      therapy administration. In the absence of an HCV vaccine, the timely monitoring
      of HCV viral load combined with the information of the viral genotype could
      contribute to patient disease management. A LightCycler Real Time RT-PCR assay
      was developed and optimized allowing rapid and accurate quantification of HCV RNA
      over an extended dynamic range using a single human reference standard. A total
      of 5,096 plasma samples, collected over almost 5 years, were tested and HCV RNA
      was quantified in 2,435 samples with levels ranging from 5.7x10(1) to 2.52x10(9)
      IU/ml. The precision and reproducibility of the test are documented by various
      inter-assay parameters of the reference standard obtained in 409 RT-PCR runs.
      This Real Time RT-PCR protocol uses the LightCycler cDNA amplicons for direct
      sequence analysis and reduces the sequencing time to approximately 3 hours.
      Nearly all HCV genotypes were identified. Viral sequences showed a similarity
      level close to 100%, independently from the viral load, while the LightCycler
      melting temperature analysis did not correlate with HCV genotypes. All this makes
      the LightCycler Real Time RT-PCR protocol a suitable tool for the diagnosis and
      monitoring of HCV infections.

PMID- 18623983
TI  - Restriction fragment length polymorphism analysis and direct sequencing for
      determination of HBV genotypes in a Turkish population.
AB  - The aim of this study was to analyze the restriction fragment length polymorphism
      and direct sequencing results in genotyping of hepatitis B virus from a Turkish
      population in a clinical virology laboratory. Serum samples of 54 chronic
      hepatitis B patients attending the Ege University Hospital were studied.
      Sequences of partial S gene PCR products were analysed and RFLP was performed.
      Fifty-three isolates could be identified by direct sequencing as genotype D. One
      sample needed to be cloned and determined as genotype D. Forty-two isolates were
      genotyped as D with RFLP according to published determinative patterns. Twelve
      isolates had undefined patterns. Eight of them suggested a mixture of isolates
      with different patterns and cloning of these samples confirmed the presence of
      heterogeneous isolates. Four isolates with undefined pattern were determined as
      genotype D by direct sequencing. All the studied isolates were genotype D. The
      results of this studied population suggest that RFLP is suitable for HBV
      genotyping in a routine clinical virology laboratory setting. However sequence
      analysis and even cloning may be needed to clarify indeterminate results.

PMID- 18623984
TI  - Detection of TTV in peripheral blood cells from patients with altered ALT and AST
      levels.
AB  - This work analyzes the prevalence of TTV DNA in peripheral blood cells from
      patients with hepatic alterations and healthy blood donors and measures levels of
      sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct
      bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) in certain randomly selected patients. DNA
      samples from 111 individuals were evaluated. They were divided into two groups,
      "A" (study) and "B" (control), including 54 patients with liver enzyme
      alterations (ALT/AST) presenting non-B-non-C hepatitis and 57 blood donors,
      respectively. TTV DNA was determined by nested PCR. Certain products of the
      second-round PCR were sequenced. Serum biochemical assay was performed and
      disclosed TTV in 31.48% (17/54) of patients in group A and 5.26% (3/57) in the
      control group B. TTV prevalence was significantly higher in patients with liver
      disease than in healthy donors. In group A, sodium, potassium, urea, creatinine,
      phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase
      (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels
      were analyzed in certain randomly selected patients and no significant difference
      in biochemical levels (p>0.05) was found when TTV infected and noninfected
      individuals were compared. Knowledge related to TTV has rapidly increased, but
      many fundamental aspects remain unclear. This led us to question the role of TTV
      and doubt remains as to whether or not it is just a commensal virus. Further
      studies are necessary to confirm and extend these findings.

PMID- 18623985
TI  - Seroprevalence of Borrelia burgdorferi infection among forestry workers and
      farmers in Duzce, north-western Turkey.
AB  - Borrelia burgdorferi infection is the most frequent tick-transmitted disease
      worldwide. Our aim was to assess the seroprevalence of B. burgdorferi infection
      among forestry workers and farmers in Duzce, in the north-west region of Turkey.
      Blood samples from 349 forestry workers and farmers and 193 healthy blood donors
      were obtained to determine the presence of antibodies to B. burgdorferi. A two
      step testing strategy was used; the sera were initially tested by ELISA and then
      by Western blot (WB) IgG. Demographic data regarding residence, age, gender,
      profession, tick bite history, contact with animals, and symptoms involving the
      skin, nervous system, and osteoarticular system were collected by questionnaire.
      All results were evaluated statistically using the chi2 test. The seroprevalence
      of B. burgdorferi was 10.9% (n=38) in forestry workers and farmers and 2.6% (n=5)
      in blood donors by ELISA, with a statistically significant difference (p<0.001).
      Seropositivity rates were related to age, gender, and common risk factors for the
      disease. IgG seropositivity was confirmed in four (1.1%) sera by WB. In this
      first seroepidemiological report from the northwest region of Turkey, tick bite
      exposure was found to be high, whereas B. burgdorferi infection was not common.
      Preventive measures against tick exposure and further studies to determine the
      distribution of Lyme disease in Turkey are proposed.

PMID- 18623986
TI  - Evaluation of random amplified polymorphic DNA analysis and antibiotic
      susceptibility application in discrimination of salmonella typhimurium isolates
      in Iran.
AB  - The purpose of this study was to determine the utility of RAPD-PCR and antibiotic
      susceptibility tests in differentiation of S. typhimurium isolates in Iran.
      Thirty isolates of S. typhimurium, selected based on animal source; place and
      time of the isolation and a reference strain of the bacterium were used in this
      study. Serotyping of the isolates was performed by reliable antisera and
      confirmed with a multiplex PCR. Genomic DNAs were extracted and subjected to an
      optimized RAPD-PCR, using two previously reported arbitrary primers (P1254 and
      23L). Bacteria were also examined for resistance against 8 antibiotics, using a
      standard antibiotic susceptibility test. While the antibiotic susceptibility test
      resulted in the identification of 13 profiles of R-type among the bacterial
      isolates, application of primers P1254 and 23L in the RAPD-PCR could discriminate
      the isolates only in four and six profiles respectively. However, combination of
      the two methods could differentiate the 30 isolates in 20 different profiles. The
      results of this study indicate that the discriminatory power of RAPD-PCR for S.
      typhimurium is low but a combination of this method with antibiotic
      susceptibility test could be considered an easy and relatively reliable
      discriminatory approach in differentiation of S. typhimurium for epidemiologic
      purposes in Iran.

PMID- 18623987
TI  - Genotyping of Legionella pneumophila serogroup 1 strains isolated in Northern
      Sicily, Italy.
AB  - During a three-year period, from April 2002 to May 2005, one hundred-forty-seven
      samples, taken from technical systems of water distribution at point of use, were
      repeatedly collected at six different sites in Northern Sicily and assayed for
      the presence of Legionella pneumophila serogroup 1 and serogroups 2 to 14. At the
      first samplings, the water distribution systems of all the sites were heavily
      contaminated, and disinfection treatments by the superheat and flush method were
      therefore performed. Treatments were always successful against L. pneumophila
      sg.1, but only in a few cases against all other serogroups. Eighty-six strains of
      L. pneumophila sg. 1, isolated from 26 of these samples, were characterized by
      amplified fragment length polymorphism (AFLP) analysis and sequence-based typing
      (SBT) procedure. Perfectly overlapping results were obtained by both the
      procedures and four genotypes were identified, accounting for all the isolates.
      The easy transferability of the SBT data through a web-based database made it
      possible to identify the presence in Northern Sicily of the two SBT types most
      commonly circulating in Europe.

PMID- 18623988
TI  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in
      Poland: further evidence for the changing epidemiology of MRSA.
AB  - This study reports the isolation of CA-MRSA strain which was found to colonize
      the nasal mucosa of a patient undergoing haemodialysis treatment. The MRSA was
      subjected to molecular analysis by Pulsed Field Gel Electrophoresis (PFGE),
      multiplex PCR assay for staphylococcal cassette chromosome mec (SCCmec) typing,
      and PCR detection of the pvl gene encoding for Panton-Valentine leukocidin. The
      analyzed MRSA harbored the SCCmec type IV and the pvl gene-two unique genetic
      markers of CA-MRSA. The PFGE pattern of the strain corresponded to the common
      European CA-MRSA (MLST Type ST80). Moreover, the strain was only resistant to
      beta-lactam agents and tetracycline. This study adds further evidence for the
      changing epidemiology of MRSA and indicates the ability of CA-MRSA to affect
      persons with established risk factors in addition to previously healthy
      individuals.

PMID- 18623989
TI  - Recovery of Enterococcus faecalis in root canal lumen of patients with primary
      and secondary endodontic lesions.
AB  - The presence of Enterococcus faecalis in root canal teeth affected by primary and
      secondary periapical lesions was studied using polymerase chain reaction (PCR)
      assays. The association between presence of E. faecalis with clinical signs of
      apical lesions was assessed to evaluate a possible relationship between clinical
      findings. Microbial samples were obtained from healthy patients affected by
      different periapical lesions, 79 teeth with primary periapical lesion and 23 with
      secondary periapical lesion. For each tooth, clinical symptoms and X-ray
      appearance were examined. E. faecalis was detected in 6 of 79 samples with
      primary lesion (7.6%), and in 9 of 23 with secondary lesion (39.1%). Suggested
      association was found between E. faecalis and secondary apical lesions. As regard
      specific signs and symptoms E. faecalis was more associated with asymptomatic
      lesions (all p<0.05) than with symptomatic apical lesions. The study confirms the
      high presence of E. faecalis in secondary apical lesions. However, its effective
      role in endodontic pathogenesis such as bone periapical lesions needs to be
      clarified.

PMID- 18623990
TI  - Transcriptional expression of fljB:z66, a flagellin gene located on a novel
      linear plasmid of Salmonella enterica serovar Typhi under environmental stresses.
AB  - A previous study identified that z66+ strain of Salmonella enterica serovar Typhi
      contains two different flagellin genes, the fliC encoding d or j antigen in
      chromosome and the fljB-like gene encoding z66 antigen in a novel linear plasmid,
      respectively. The promoter of fljB:z66 is different from that of fliC:d/j and
      z66+ strain alters flagellin expression in only one orientation, from z66 to d
      orj antigen, raising the suspicion that z66+ strain is a special biphasic strain.
      To clarify the expressional characteristics of flagellin genes of z66+ strain,
      expression patterns of fljB:z66 and fliC were investigated by RT-PCR under a
      series of environmental stresses during infection, such as acidic stress, osmotic
      stress, bile acid stress and oxidative stress. Results showed that the expression
      level of fljB:z66 is over 10-fold higher than the level of fliC in low and middle
      osmotic conditions before stresses. Only the expressional regulatory tendency of
      fljB:z66 in response to bile acid stress is similar to that of fliC. Differential
      expressional patterns between fljB:z66 and fliC of S. enterica serovar Typhi were
      seen under osmotic stress, bile acid stress and oxidative stress. These results
      support the hypothesis that the z66+ strain is a special biphasic strain of S.
      enterica serovar Typhi.

PMID- 18623991
TI  - Chlamydia trachomatis detection in a population of asymptomatic and symptomatic
      women: correlation with the presence of serological markers for this infection.
AB  - A study of 371 women (261 asymptomatic and 110 symptomatic subjects with clinical
      PID) was performed to detect the presence of Chlamydia trachomatis (C.t.) and to
      correlate the serological markers against this microrganism, such as antibody to
      chlamydial hsp60 (Ab-Chsp60) and different levels of IgG, IgM and IgA, with
      epidemiology, pathology, sexual habits, age, diagnostic methods in the groups of
      women with and without pelvic inflammatory disease (PID). We found a
      statistically significant difference between the asymptomatic and symptomatic
      women regarding the presence of C.t. (3.4% versus 20%; p<0.0001). This presence
      was affected by the age of women (more in the group < or =25 years old), by
      having sex with new partners mainly if they did not undergo an antibiotic
      treatment. The association of antibody Chsp60 with the presence of clinical PID
      was quite striking. We also found a strict correlation between the detection of
      Ab-Chsp60 and previous chlamydial infection as well as between Ab-Chsp60 and
      elevated serum chlamydial IgG or IgA levels. Due to these findings, we can say
      that the use of serological markers for C.t. in clinical practice may be an
      important tool for an early screening and diagnosis of women at high risk of
      chlamydial infection.

PMID- 18623992
TI  - Comparison of microdilution method and E-test procedure in susceptibility testing
      of caspofungin against Candida non-albicans species.
AB  - It is widely known that systemic and mucosal candidiasis caused by Candida non
      albicans strains endangers the lives of hospitalised patients since these
      pathogens are extremely difficult to defeat by commonly used antifungal agents.
      The present study determined the in vitro activities of a novel antimicotic drug 
      caspofungin - against 76 Candida non-albicans isolates by means of the CLSI
      reference method for broth dilution antifungal susceptibility testing of yeasts
      and the E-test procedure for comparison. Caspofungin was efficacious against the
      majority of strains tested, with the average MICs90 evaluated by the
      microdilution method and E-tests amounting to 1 mg/l and 0.5 mg/l, respectively.
      Since the agreement between MICs within +/-2 dilutions obtained by these two
      techniques was 92% (Kappa coefficient of 0.92), the E-test procedure seems to be
      a reliable alternative to the broth microdilution method and may provide another
      choice for clinical laboratories.

PMID- 18623993
TI  - Genetic typing of bovine viral diarrhoea virus: evidence of an increasing number
      of variants in Italy.
AB  - Bovine Viral Diarrhoea Virus (BVDV) is responsible worldwide for severe economic
      losses on cattle farms. BVDV is an RNA virus with a high genome variability
      having practical consequences on epidemiology, diagnosis and disease control.
      Genetic monitoring was suggested as the first step in BVDV control. Thirty-seven
      Bovine Viral Diarrhoea Viruses were identified in persistently infected cattle,
      mucosal disease-affected animals and in bulk milk, and were characterised
      genetically. The 5'UTR region was amplified and sequenced, and a phylogenetic
      analysis was carried out comparing all the Italian sequences of BVDV available
      from the Genbank database. An unusual number of persistent infected animals was
      evidenced on more than one farm. Phylogenetic analysis attributed all our viruses
      to BVDV type I and distinguished four different subgroups inside this genotype.
      Analysis of old and new viruses revealed the circulation of viruses classified in
      subgroups BVDV Ia and Ij never reported in Italy.

PMID- 18623994
TI  - Rapid and sensitive detection of MS2 coliphages in wastewater samples by
      quantitative reverse transcriptase PCR.
AB  - Coliphage MS2 is used in place of pathogens in many studies and is considered one
      of the indicators of pathogenetic viruses in wastewater. We developed a
      quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay to
      quantify MS2 coliphages in treated wastewater samples. The format used was SYBR
      Green. The assay included an internal control to disclose the presence of PCR
      product inhibitors. The method had a wide dynamic range (8 logs) with a
      correlation coefficient of 0.999 and is capable of detecting as few as 4x10(2)
      genome equivalents/100 ml of wastewater sample. The method was validated by using
      artificially contaminated water samples. The validated method was then applied to
      naturally contaminated samples collected in a wastewater treatment plant and the
      results were compared with those obtained by a plaque assay. In comparison with
      the plaque assay the PCR-method yielded viral counts about 1.5 orders of
      magnitude higher. The entire detection method, including sample processing and
      real-time PCR amplification, was completed within 4 hours, making it a rapid
      single-day method.

PMID- 18623995
TI  - First Italian case of cyclosporiasis in an immunocompetent woman: local acquired
      infection.
AB  - Cyclospora cayetanensis is a coccidian agent of chronic diarrhea in humans with a
      worldwide distribution. We report the first documented case of acquired
      Cyclosporiasis in Italy. The patient was an immunocompetent woman with no recent
      history of travel outside the country. Microscopy detected Cyclospora oocysts in
      a feces sample. PCR detected the pathogen in a second sample, which had tested
      negative by microscopy. The patient was investigated to detect other
      microorganisms in feces, such as Salmonella spp., Shigella spp, Campylobacter
      spp., Yersinia spp, and enteroviruses: all were negative. All symptoms
      disappeared 72 h after the beginning of therapy.

PMID- 18623996
TI  - Churg-Strauss syndrome: a diagnosis not to be forgotten.
AB  - Churg-Strauss syndrome (CSS) is a peculiar form of vasculitis with involvement of
      small- and medium-size arteries, histologically characterized by necrotizing
      granulomas in vessel walls and in perivascular tissues. The Authors report a case
      of CSS occurred in a young man being treated with corticosteroids for a diagnosis
      of asthma. The patient was hospitalized because of fever, diarrhoea and abdominal
      pain; the first assessment showed leucocytosis and eosinophilia,increase in
      flogosis indexes and anti-pANCA antibodies positive. A few days later an acute
      peritonitis with multiple intestinal perforations occurred and a partial
      resection of small bowel was performed,followed by another resection of an ileal
      segment because of a new double perforation close to the previous intestinal
      anastomosis. In the bowel resection pieces necrotizing vasculitis and
      granulomatous infiltrates involving lymphocytes and eosino- phils were observed.
      Although the severe intestinal involvement and especially the symptoms
      necessitating iterative surgery were significant factors of poor prognosis the
      patient was successfully treated firstly with metylprednisolone only and then
      with monthly administration of immunosuppressive drugs combined with lower daily
      dose of steroids. The CSS diagnosis is not to be forgotten althoughits early
      clinical features can be frequently mistaken for an allergic disease; an early
      diagnosis can allow to perform the best treatment, to reach the disease remission
      and to improve the quality of life of the patients.

PMID- 18623997
TI  - Microbiological features of acute bacterial conjunctivitis in a central Italian
      area.
AB  - The study aims to identify bacteria causing conjunctivitis in a central Italian
      area and to analyze chemosusceptibility. From 2005 to 2006, 91 conjunctival swabs
      were collected from acute conjunctivitis cases and screened for common bacteria
      and fungi. Susceptibility tests were performed on isolates. Staphylococcus
      aureus, Streptococcus pneumoniae and Haemophilus influenzae amounted to 86.2%.
      Overall, 100% of strains were susceptible to chloramphenicol and 96.6% to
      quinolones. Conversely, 20.7% of isolates were tetracycline-resistant and, even
      if all Gram negative isolates were susceptible to gentamicin, the most frequently
      isolated pneumococci are constitutively resistant. The study provides support for
      a rational choice of empiric therapy.

PMID- 18623998
TI  - A diagnosis of pneumococcal peritonitis secondary to pyo-salpinx in a young
      healthy female by culturing peritoneal pus.
AB  - Pneumococcal intra-abdominal infections of female genital tract origin are rare.
      A 33-year-old woman with peritonitis due to Streptococcus pneumoniae serotype 3
      was reported. The patient did not have any of the known predisposing conditions
      for intra-abdominal pneumococcal infection. The clinical presentation included
      signs of multiorgan failure. Peritoneal toilette, bilateral salpingectomy and
      antibiotic treatment were promptly administered. The patient remained febrile,
      developed respiratory failure and required a repeated laparotomy and a prolonged
      antimicrobial treatment. Penicillin susceptible S. pneumoniae was isolated from
      the pus collected at surgery. Thus, culturing of intra-operative specimens should
      never be neglected to establish the correct microbiologic diagnosis.

PMID- 18623999
TI  - Microbiological and clinical periodontal effects of fixed orthodontic appliances
      in pediatric patients.
AB  - The aim of this study was to evaluate changes of microbiota in ten patients
      undergoing orthodontic treatment. For each patient clinical examination of
      gingival index (GI) and plaque index (PI) were performed at the first molars at:
      baseline (T1), 2 (T2), 4 (T3) and 12 weeks (T4). At the same time subgingival
      plaque and tongue samples were taken for the microbiological study. Clinical
      results showed that at T4, the mean PI score was significantly lower than T1 and
      the GI was markedly reduced. Microbiological results showed that at T1 and T4
      facultative aerobic bacteria were prevalent, whereas anaerobic bacteria were more
      common at T2 and T3.

PMID- 18624000
TI  - [Intoxication with magnesium, a 'forgotten' electrolyte].
AB  - Magnesium salts are widely used and are usually regarded as rather harmless.
      Magnesium intoxication, however, can be lethal. Recently, severe magnesium
      intoxication was identified in 3 patients, one woman aged 68 and 2 men aged 19
      and 26 years respectively, who required treatment in an Intensive Care setting.
      Initial symptoms of magnesium intoxication went unnoticed due to sedation or
      paraplegia. Only after developing severe neurological symptoms, respiratory or
      circulatory failure, magnesium intoxication was diagnosed. Plasma magnesium
      levels exceeded 6 mmol/l (reference value: 0.70-1.00). Therapy consisted of
      cessation of magnesium therapy, administration of calcium and enhanced
      elimination of magnesium by haemodialysis. All patients survived the
      intoxication. Magnesium intoxication may develop unnoticed when the initial signs
      and symptoms are masked by clinical conditions. Especially patients with renal
      failure, inflammatory bowel disease, sedation and paraplegia need careful
      monitoring when magnesium is administered.

PMID- 18624001
TI  - [Selective publication of research into antidepressants: consequences for the
      practice guideline 'depression'].
AB  - It was recently shown in a publication in The New England Journal of Medicine
      that the publicly accessible information about the effectiveness of
      antidepressive medication is incomplete and biased. The authors calculated from
      published and unpublished data that the effectiveness of antidepressants as
      published in the literature is overestimated probably by 32%. Based on this
      publication and other publications questioning the effectiveness of
      antidepressants, adjustment of the Dutch practice guideline for depression is
      proposed: only severely depressed patients should be treated with
      antidepressants. Some measures to prevent publication bias are also proposed.
      These require the cooperation of all parties participating in registration
      ofdrugs and publication of drug research.

PMID- 18624002
TI  - [Delayed cord clamping in the interest of the newborn child].
AB  - The importance of delayed cord clamping, both for the preterm and for the term
      newborn, for the prevention ofneonatal anaemia (during the neonatal period and/or
      at the age of3 months) and furthermore to reduce the need of blood transfusions,
      has recently been demonstrated in controlled clinical studies and meta-analyses.
      Physiological and pathophysiological factors also provide a rationale for delayed
      cord clamping: neonatal blood volume may increase by 32% if cord clamping is
      delayed until the umbilical cord has completely stopped pulsating. A slow
      transition, involving closure of the ductus arteriosus and the foramen ovale
      cordis and gradual filling of the neonatal systemic circulation, contributes to
      the opening of the alveoli due to perfusion of the alveolar capillaries. No
      disadvantages, such as polycythaemia or hyperbilirubinaemia, have been described
      with regard to preterm neonates, whereas the incidence of intracranial
      haemorrhages is reduced. Also for the mother, no disadvantages of late clamping
      have been determined. As a standard procedure, the baby's umbilical cord should
      not be clamped until at least 3 minutes have passed. One should wait at least 30
      seconds during the birth of children for whom a more active approach is
      necessary. Of all people, these children will benefit from a good Hb level.

PMID- 18624003
TI  - [Immune activation and depression in the elderly].
AB  - Besides the monoamine hypothesis, the stress hypothesis and the vascular
      hypothesis, the inflammatory hypothesis might be an etiological explanation for
      late-life depression. There is a growing amount of evidence to support this
      hypothesis. In animal studies, injection with cytokines was shown to cause
      behavioural changes ('sickness behaviour') similar to depressive symptoms in
      humans. Cytokine treatment of certain tumours and chronic hepatitis can also
      cause depressive symptoms. The prevalence of depression in patients with
      autoimmune diseases is higher than in the general population. Etanercept had a
      favourable effect on the depressive symptoms in patients with psoriasis,
      independent of improvement of physical symptoms. Cytokines affect the
      hypothalamus-pituitary-adrenal axis and cerebral neurotransmitter systems, both
      of which are thought to be involved in depression. Immune activation has been
      associated with depression, and several anti-depressive treatments affect immune
      parameters, although inconsistently. Since the aging process is associated with a
      dysregulation of the immune system, the inflammation hypothesis might be
      particularly true in late-life depression.

PMID- 18624004
TI  - [Diagnostic image (378). A woman with a subungual pigmentation of the left
      hallux].
AB  - An 81-year-old woman presented with a subungual pigmented lesion of the left
      hallux, caused by a malignant acral-lentiginous melanoma.

PMID- 18624005
TI  - [Need for blood transfusion in premature infants in 2 Dutch perinatology centres
      particularly determined by blood sampling for diagnosis].
AB  - OBJECTIVE: Determination of factors related to the need for transfusion in
      premature infants. DESIGN: Descriptive. METHOD: The need for transfusion in
      premature infants was determined in 2 academic centres: University Medical Center
      Utrecht and Leiden University Medical Center, The Netherlands. The data had been
      acquired in another study. The factors under study were: hospital, pregnancy
      duration, birth weight, gender, time of clamping of the umbilical cord, total
      volume of blood sampled for diagnostic purposes, number of days of mechanical
      ventilation, total duration of admission and duration of the admission to the
      Neonatal Intensive care unit. Both hospitals followed the national
      interdisciplinary practice guideline 'Blood transfusion'. RESULTS: The total
      volume ofsampled blood for diagnosis, the duration of the mechanical ventilation
      and the admission period were related to a greater need for transfusion. On the
      other hand, the chance of transfusions diminished with longer pregnancy duration
      or increased birth weight. The difference in need for blood transfusion between
      both centres was significant. The total volume of transfused erythrocytes showed
      a strong correlation with the volume sampled for diagnostic procedures.
      CONCLUSION: Anaemia in neonates is strongly related to the amount of blood taken
      for diagnostic procedures. Alternatives for blood transfusions in premature
      infants, and consequently for the reduction of the number of donors per child,
      are to be sought in delayed clamping of the umbilical cord, use of erythropoietin
      and use ofautologous umbilical cord blood.

PMID- 18624006
TI  - [Chronic hepatitis B virus (HBV) infection: usefulness of the combination of
      HBeAg and ALT determination to predict a high HBV-DNA level and therefore the
      necessity of referral to a specialist for possible antiviral treatment].
AB  - OBJECTIVE: To assess the usefulness of a simple practical guideline based on
      hepatitis B e-antigen (HBeAg) status and a single alanine aminotransferase (ALT)
      determination to predict hepatitis B virus (HBV) load in chronic HBV patients as
      a criterion for referral to a specialist for possible antiviral therapy. DESIGN:
      Prospective observational study. METHOD: 420 patients with chronic HBV infection
      were seen at the Municipal Health Service (MHS) in Rotterdam between 2002 and
      2005. The usefulness ofa guideline based on HBeAg positivity and/or elevated ALT
      levels to predict high HBV DNA levels (defined as more than 10(5) copies/ml) was
      determined. Patients with HBeAg or an elevated ALT level were referred to a
      specialist according to the practical guideline. Positive and negative predictive
      value, sensitivity, and specificity of the referral guideline for a high HBV-DNA
      level were calculated. RESULTS: Less than half, 43% (181/420) of the patients,
      were eligible for referral to specialist care. The positive predictive value of
      the referral guideline was 45% (82/181, 95% CI: 38-53). The negative predictive
      value, i.e. the proportion of patients with low viral loads who were (rightly)
      not selected for referral, was 95% (227/239; 95% CI: 71-97). The sensitivity was
      87% (95% CI: 80-93): the patients selected included 82 of 94 patients with a high
      HBV DNA level. Of the 12 patients with high viral loads not referred according to
      the guideline, 11 had a viral load of between 10(5)-10(6) copies/ml. CONCLUSION:
      A referral guideline based on HBeAg status and a single ALT determination can
      successfully predict viral load in chronic HBV patients and can be used in
      primary care to select patients for referral to specialist care. This guideline
      may limit the number of unnecessarily referred patients, enhancing the efficiency
      of the care for patients with chronic HBV infection.

PMID- 18624007
TI  - [Spinal epidural abscess as a complication of a finger infection].
AB  - An 81-year-old man was treated with intravenous antibiotics for a soft tissue
      infection in a finger. Despite adequate antibiotic treatment, he developed signs
      of spinal cord injury caused by a cervical spinal epidural abscess. An emergency
      laminectomy was performed. The neurological impairment appeared to be
      irreversible, and the patient died. Spinal epidural abscess is a rare and serious
      complication ofa bacteraemia. It is often caused by an infection of the skin or
      soft tissue with Staphylococcus aureus. Given the risk of rapidly progressive and
      irreversible neurological damage, this complication must be treated as soon as
      possible. The treatment of choice is surgery. Conservative management with
      intravenous antibiotics is an option only under strict conditions.

PMID- 18624008
TI  - [Progressive, ascending neurological impairment: a spinal epidural abscess that
      presents as Guillain-Barre syndrome].
AB  - Over the course of 4 days, a 65-year-old man developed fever and thoracic back
      pain, followed by weakness and sensory changes in both legs. Physical examination
      revealed dyspnoea, subfebrile temperature, neck pain withoutnuchal rigidity,
      sensory impairment, areflexia and weakness in both legs (and arms to a lesser
      extent). Guillain-Barre syndrome was considered, and treatment with intravenous
      immunoglobulins was started. The patient nevertheless developed respiratory
      insufficiency, progressive leg paresis and nuchal rigidity. Spinal MRI revealed
      an extensive cervicothoracic epidural abscess. Surgical decompression and
      drainage were performed, followed by antibiotic treatment; the patient recovered
      and was able to walk with assistance. A spinal epidural abscess can be difficult
      to recognise and is potentially lethal. The diagnosis should be considered in
      patients with fever and back pain, especially when these coincide with symptoms
      of neurological impairment. The efficacy of therapy depends on timely
      recognition; to this end, neuroimaging with MRI is essential.

PMID- 18624009
TI  - [Podcasts at The Nederlands Tijdschrift voor Geneeskunde, a first new product].
AB  - Podcasts become increasingly available for many biomedical journals. Since the
      beginning of this year the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal
      of Medicine) has been uploading podcasts on a weekly basis. With this the journal
      offer its readers audio summaries and interviews with authors for free
      (www.ntvg.nl).

PMID- 18624010
TI  - [Three patients with tuberculous meningitis: treatment started at tentative
      diagnosis].

PMID- 18624011
TI  - [Serious concerns regarding research linking cot death with child day care].

PMID- 18624012
TI  - Summary health statistics for the U.S. population: National Health Interview
      Survey, 2006.
AB  - OBJECTIVE: This report presents both age-adjusted and unadjusted health
      statistics from the 2006 National Health Interview Survey (NHIS) for the civilian
      noninstitutionalized population of the United States, classified by sex, age,
      race, Hispanic or Latino origin and race, education, family income, poverty
      status, health insurance coverage (where appropriate), place of residence, and
      region of residence. The topics covered are respondent-assessed health status,
      limitations in activities, special education or early intervention services,
      injury and poisoning episodes, health care access and utilization, and health
      insurance coverage. SOURCE OF DATA: NHIS is a household, multistage probability
      sample survey conducted annually by interviewers of the U.S. Census Bureau for
      the Centers for Disease Control and Prevention's National Center for Health
      Statistics. In 2006, household interviews were completed for 75,716 persons
      living in 29,204 households, reflecting a household response rate of 87.3%.
      SELECTED HIGHLIGHTS: Nearly 7 in 10 persons were in excellent or very good health
      in 2006. About 36 million persons (12%) were limited in their usual activities
      due to one or more chronic health conditions. About 4 million persons (2%)
      required the help of another person with activities of daily living, and about 8
      million persons (4%) required the help of another person with instrumental
      activities of daily living. About 6% of children received special education or
      early intervention services. Among persons under age 65 years, about 43 million
      (17%) did not have any health insurance coverage. The most common reason for
      lacking health insurance was cost, followed by a change in employment.

PMID- 18624013
TI  - Improving the psychosomatic competence of medical doctors in China, Vietnam and
      Laos-the Asia-Link Program.
AB  - OBJECTIVE: The European Union is supporting a 3-year cooperation project
      coordinated by the Freiburg University Clinic for the development and promotion
      of psychosomatic medicine in China, Vietnam, and Laos. The main objective is the
      development and performance of post-graduate training for medical doctors to
      improve doctor-patient communication and to acquire psychosomatic knowledge,
      skills, and attitudes. METHOD: The project is based on contacts which have
      existed for several years with the Tongji University and the affiliated Tongji
      Hospital in Shanghai. Medical doctors in all disciplines are to learn to promptly
      recognize emotional disorders which frequently present in the primary care
      setting, to offer limited treatment themselves, and to cooperate with mental
      health specialists. RESULTS: In the first year of the project, 50 medical doctors
      from different medical fields were trained as future teachers. In the second
      year, we are starting a pilot curriculum which will include 60 hours of theory
      and psychosocial interventions, divided into three blocks. CONCLUSIONS: Future
      developments will involve setting up a psychosomatic network in Southeast Asia to
      establish advanced training in psychosomatic medicine and psychotherapy and to
      promote psychiatric and psychosomatic consultation and liaison services in the
      general hospitals.

PMID- 18624014
TI  - Assessing the prevalence of depression among individuals with diabetes in a
      Medicaid managed-care program.
AB  - OBJECTIVES: To determine the prevalence of self-reported depression symptoms
      among diabetic individuals enrolled in Gold Choice, a Medicaid managed care
      organization specifically for people with mental health and/or substance abuse
      diagnoses; and to assess the sensitivity and specificity of individuals' self
      report with encounter data. METHODS: The 9-item depression scale of the Patient
      Health Questionnaire (PHQ-9) was mailed to 454 Gold Choice members in Western New
      York diagnosed with diabetes; and 249 completed PHQ-9 forms were returned (55%
      response rate). The PHQ-9 forms were compared to primary care encounter data to
      determine whether the respondents had been diagnosed with depression. Descriptive
      and inferential statistical analysis was undertaken. RESULTS: The majority (56%)
      of individuals in the sample screened positive for depression (PHQ-9 > or = 10),
      and half (49%) did not have evidence of a diagnosis in their encounter data. The
      percentage of those diagnosed with depression rose with increasing PHQ-9 severity
      levels, with 63% of individuals with the most severe depression (PHQ-9 > or = 20)
      having a diagnosis. This trend was statistically significant, confirmed by
      independent sample t-tests and chi-square tests. The sensitivity of the PHQ-9 was
      moderate (66%), as was the specificity (52%). CONCLUSIONS: The results of this
      study suggest that depressive disorders may be under-recognized and under-treated
      amongst individuals with diabetes in the primary care setting. Half (51%) of
      those with PHQ-9 scores > or = 10 had depression diagnoses, suggesting poor
      compliance rates and/or a need for therapy reassessment.

PMID- 18624015
TI  - Benefits of consumer psychoeducation: a pilot program in South Africa.
AB  - OBJECTIVE: Previous studies have indicated that patient adherence to
      antidepressant treatment is unsatisfactory. There is, however, little published
      data on adherence in the South African context. In this pilot study we explore
      the possible benefits of a consumer psychoeducation program. METHOD: First, drop
      out rates during the first four months of paroxetine treatment were surveyed in
      patients participating in a psychoeducational program focused on depression and
      its treatment. Practitioners were also surveyed about their perceptions of the
      program. Second, drop-out rates during the first four months of paroxetine
      treatment were estimated from a pharmacy database of selective serotonin reuptake
      inhibitor (SSRI) prescriptions in South Africa. RESULTS: Patients who
      participated in a psychoeducational program demonstrated comparatively lower drop
      out rates during treatment compared with drop-out rates in patients on paroxetine
      (and other SSRIs) obtained from a national pharmacy database. Improved adherence
      on the psychoeducational program was attributed to an increased understanding of
      depression and the need to take medication, a realization that patients are not
      alone (i.e., depression is a widespread problem) and a better understanding and
      acceptance of the possible side-effects of medication. Both practitioners and
      patients were positive about their experience of the program and 80% of doctors
      judged the program to be very useful. CONCLUSION: Drop-out rates during SSRI
      treatment in South Africa appear to be unacceptably high, whether or not patients
      receive concomitant benzodiazepines. Psychoeducational programs may prove
      valuable in increasing adherence to treatment regimes.

PMID- 18624016
TI  - Relationship between depression and quality of life in persons with HIV infection
      in Nigeria.
AB  - OBJECTIVE: Despite the fact that two-thirds of all the people with HIV live in
      sub-Saharan Africa, little is known about the emotional state and quality of life
      (QOL) of subjects with HIV in this region. The objective of this study was to
      evaluate the association between clinical depression and quality of life in a
      group of HIV sero-positive subjects in Nigeria. METHODS: Subjects with HIV
      infection (n = 87) completed a questionnaire detailing sociodemographic and HIV
      related variables. The subjects were assessed for the diagnosis of depression
      using the Mini International Neuropsychiatric Interview (MINI) and their
      subjective health related quality of life (QOL) was assessed using the short
      version of the WHO quality of life scale (WHOQOL-BREF). RESULTS: There were 25
      (28.7%) subjects with diagnosis of depression. Lower educational level correlated
      with poorer QOL in all the domains of WHOQOL-BREF except the "social
      relationship" domain. Also, poor social support correlated with poorer QOL scores
      on domains of "physical health" and "social relationship" and presence of medical
      problems was significantly associated with poorer scores on domains of "physical
      health" and "psychological health." Diagnosis of depression was significantly
      correlated with poorer QOL in all domains except the "social relationship"
      domain. CONCLUSION: Poorer health related QOL in Nigerian subjects with HIV was
      associated with depression, lower educational and socioeconomic levels, and poor
      social support. Early identification and referral of patients with depression
      needs to be incorporated into intervention programs designed for HIV infected
      individuals in this region.

PMID- 18624017
TI  - Borderline personality symptomatology and sexual impulsivity.
AB  - OBJECTIVE: According to the Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition, borderline personality disorder (BPD) is an Axis II
      phenomenon that is characterized by impulsivity, including sexual impulsivity.
      However, little empirical research has been undertaken to confirm and/or define
      the nature of sexual impulsivity in patients with BPD, which is the focus of the
      present study. METHOD: Using a cross-sectional approach and sample of
      convenience, we surveyed 76 women who were being seen as outpatients in an
      internal medicine clinic regarding: a) borderline personality symptoms using two
      measures (i.e., the borderline personality scale of the Personality Diagnostic
      Questionnaire-4, McLean Screening Inventory for Borderline Personality Disorder);
      and b) their sexual histories. RESULTS: We found two statistically significant
      differences--those with borderline personality symptomatology were more likely to
      have an earlier onset of sexual intercourse as well as to report date rape.
      CONCLUSIONS: Individuals with borderline personality symptomatology report
      earlier sexual exposure as well as date rape, but not other aspects of sexual
      impulsivity such a greater number of sexual partners, more frequent treatment for
      sexually transmitted diseases, etc.

PMID- 18624018
TI  - Multiple episodes in children and adolescents with bipolar disorder: comorbidity,
      hospitalization, and treatment (data from a cohort of 8,129 patients of a
      national managed care database).
AB  - OBJECTIVE: The purpose of this study was to delineate the prevalence, demographic
      characteristics, comorbidity, hospitalization, and medication use of a large
      cohort of patients with and without multiple episodes per year. We hypothesized
      that children and adolescents with multiple episodes per year would have a higher
      comorbidity and require more hospitalizations and pharmacological treatment than
      their counterparts without multiple episodes. METHODS: Analysis was conducted on
      a cohort of 8,129 children and adolescents patients (< or = 18 y.o.) with bipolar
      disorders (BD), from the Integrated Healthcare Information Services (IHCIS)
      identified from June 30, 2000 to July 1, 2003. Demographics variables, type of
      hospitalization, and psychotropic medication used in the year of follow-up were
      compared between children and adolescents with multiple and those without
      multiple episodes per year. RESULTS: Included were 58 patients with multiple
      episodes (defined as: > or = 4 or more reports of inpatient treatment for any
      affective disorders per year) and 8,071 without multiple episodes. Children and
      adolescents with multiple episodes versus those without multiple episodes were
      differentiated as follows: more comorbid attention deficit disorder (ADD) (80.9%
      versus 29.4%) (chi2 = 70.61, df = 1, p < 0.0001); higher rate of hospital
      admission for depression (12.1% vs. 1.8%, chi2 = 27.86, df = 1, p < 0.0001); for
      other psychiatric conditions (48.3% vs. 11.2, chi2 = 74.47, df = 1, p < 0.0001)
      and for medical conditions (22.4% vs. 3.9%, chi2 = 46.26, df = 1, p < 0.0001).
      Patients with multiple episodes per year were more likely than those without
      multiple episodes to be given mood stabilizers (91.4% vs. 60.3%, chi2 = 22.02, df
      = 1, p < 0.0001), antidepressants (79.3% vs. 59.2%, chi2 = 8.82, df = 1, p =
      .0003), and antipsychotics (89.7% vs. 45.8%, chi2 = 42.91, df = 1, p < 0.0001).
      The use of stimulants did not differ between the two groups (24.1% vs. 23.0%),
      chi2 = 0.02, df = 1, p = 0.96). CONCLUSIONS: Our findings support previous
      studies demonstrating that children and adolescents with multiple episodes per
      year present a higher comorbidity and require more hospitalizations and
      pharmacological treatment than those without multiple episodes. The diagnosis and
      treatment of children and adolescents with BD will have to take into account the
      high comorbidity of ADD mainly in children and adolescents with multiple
      episodes. Future prospective studies will help to better characterize the impact
      of multiple episodes in the course of pediatric BD and facilitate appropriate
      treatment strategies.

PMID- 18624019
TI  - Barriers to care-seeking for depressed African Americans.
AB  - OBJECTIVE: We explored perceived barriers to mental health care-seeking for
      depressed, low-income African Americans who are already engaged in psychotherapy.
      METHODS: During a trial to improve psychotherapy appointment adherence, we asked
      all African-American participants, "Research shows African Americans with
      emotional or psychological problems use mental health services at half the rate
      of whites with similar problems. Why do you think that is?" Responses were
      captured verbatim. RESULTS: Of 53 African Americans enrolled, 43 completed the
      study. We analyzed their responses in the hope of identifying modifiable
      responses. We used qualitative analytic methods, with four raters achieving
      consensus in coding responses into 13 thematic categories. Stigma was the most
      frequent response, followed by dysfunctional coping behavior, shame, denial, and
      "don't know." CONCLUSION: While this study supports several barriers to care
      seeking reported in the extant literature, our data also underscores the
      prominence of shame and denial, together with their complex interrelationships to
      public stigma and depression, respectively. Future research should assess the
      relationships between these factors to mental health care-seeking behavior in low
      income African Americans and ways of modifying them.

PMID- 18624020
TI  - Serotonergic antidepressants and linezolid: a retrospective chart review and
      presentation of cases.
AB  - OBJECTIVE: To report the results from a retrospective chart review looking at the
      combination of linezolid and serotonergic antidepressants and to report two cases
      of serotonin syndrome which were identified at our hospital. CASE SUMMARY: During
      the retrospective chart review one case of serotonin syndrome was identified. A
      65-year-old female was receiving escitalopram for the treatment of depression
      prior to admission. Linezolid therapy was initiated on admission and two days
      later the patient had a tonic-clonic seizure. Escitalopram was discontinued and
      the patient did not have any further seizure activity. In a second case, a 37
      year-old male was receiving citalopram during hospitalization and was started on
      concomitant linezolid. The patient had myoclonus and was observed to be tremulous
      throughout therapy with linezolid. Ten days after discontinuation of linezolid
      the patient continued to have symptoms until the withdrawal of citalopram. The
      Naranjo probability scale scores the first case as possibly related and the
      second case as probably related to the combination. DISCUSSION: It has been well
      documented in the literature that the combination of linezolid and serotonergic
      antidepressants may cause serotonin syndrome. In this retrospective chart review
      only one patient of 53 (1.8%) had symptoms highly suggestive of serotonin
      syndrome. A second patient continued to have symptoms of serotonin syndrome even
      after withdrawal of linezolid. CONCLUSIONS: This retrospective review and
      subsequent case reports confirm the rare, but serious, potential of serotonin
      syndrome associated with the combination of linezolid and serotonergic
      antidepressants.

PMID- 18624021
TI  - Anxiety and unrecognized high blood pressure in U.S. ambulatory care settings: an
      analysis of the 2005 National Ambulatory Medical Care Survey and the National
      Hospital Ambulatory Medical Care Survey.
AB  - OBJECTIVE: To determine for U.S. ambulatory visits for anxiety how often high
      blood pressure is unrecognized and the factors associated with being
      unrecognized. METHODS: Analyzed data from the 2005 National Ambulatory Medical
      Care Survey and National Hospital Ambulatory Medical Care Survey looking at
      visits for anxiety by patient complaint or provider diagnosis and determined if a
      hypertension diagnosis was included for visits in which measured blood pressure
      was in the hypertensive range. This was compared to total visits in the NAMCS and
      NHAMCS. Logistic regression determined predictors of high blood pressure going
      unrecognized for visits for anxiety. RESULTS: Of visits for anxiety in 2005 with
      elevated blood pressure, 32.5% were unrecognized. This compares to 24.6%
      unrecognized for all visits with hypertension/elevated blood pressure. At visits
      in which anxiety medications were prescribed (OR 2.44 95% CI 1.01-5.89) and for
      Hispanic ethnicity (OR 13.9 95% CI 1.46-132.03), high blood pressure was more
      likely to be unrecognized. High blood pressure was less likely to be unrecognized
      for those 45 to 64 years old (OR 0.21 95% CI 0.07-0.62), visits not with the
      primary care provider (OR 0.09 95% CI 0.03-0.33), visits for a chronic problem
      (OR 0.26 95% CI 0.08-0.86), and visits at which anti-hypertensive medications
      were prescribed (OR 0.005 95% CI 0.001-0.04). CONCLUSIONS: Anxiety is a common
      reason for visits in U.S. ambulatory settings. Many of these visits have
      concomitant high blood pressure, a large proportion of which may go unrecognized.
      Efforts to educate physicians about these issues may help reduce the level of
      unrecognized high blood pressure in those with anxiety.

PMID- 18624022
TI  - Prevalence of metabolic syndrome among inpatients with schizophrenia.
AB  - OBJECTIVE: Cardiovascular disease is one of the most prevalent factors
      responsible for excess mortality in schizophrenia. Metabolic syndrome (MetS) is
      associated with the development of coronary heart disease and diabetes mellitus.
      The aim in this cross-sectional study was to assess the prevalence of MetS in
      schizophrenic Turkish inpatients. METHOD: The study was conducted from January
      2006 to June 2006, and included 231 patients with schizophrenia. All participants
      were enrolled from inpatients attending the Samsun Mental Health Hospital
      psychiatry clinic. All subjects were aged between 18 and 65 and met the DSM IV
      criteria for schizophrenia. MetS was taken as central obesity (defined as waist
      circumference: men > or = 94 cm, women > or = 80 cm) and meeting > or = 2 of the
      following abnormalities described by the International Diabetes Federation (IDF):
      a serum triglyceride level > 150 mg/dL, high-density lipoprotein (HDL)
      cholesterol < 40 mg/dL in men and < 50 mg/dL in women, blood pressure > or =
      130/85 mm Hg, and a fasting serum glucose level > or = 100 mg/d/L. RESULTS: The
      study group consisted of 174 male and 57 female patients. Mean age was 38.5 +/-
      10.5 and mean duration of illness was 15.76 +/- 9.95 years. The overall
      prevalence of MetS diagnosed according to the IDF criteria was 32.0% (n = 74) and
      was higher in females (61.4%) than in males (22.4%; p = 0.0001). In logistic
      regression analysis the last step of the regression model was gender (B = 1.70, p
      = 0.0001, OR = 5.50, 95% CI = 2.90-10.45). CONCLUSION: This study shows that the
      prevalence of MetS in Turkish patients with schizophrenia is similar to that of
      the general population, but lower than in other reports regarding the
      schizophrenia population.

PMID- 18624023
TI  - Spiritual and religious involvement relate to end-of-life decision-making in
      patients undergoing coronary bypass graft surgery.
AB  - Settling one's end-of-life affairs in the face of coronary artery bypass graft
      surgery (CABG) can be both distressing and beneficial for individuals who are
      facing imminent threat of death. Religious thoughts, common in this context, may
      offer some comfort and support for facing this process. However, few empirical
      studies have addressed the role of religious or spiritual involvement in the
      settling of one's end-of-life affairs in cardiac patients. This prospective study
      investigated the effect of religious and spiritual factors on whether decisions
      regarding end-of-life had been made in a sample of middle-aged and older patients
      undergoing CABG. In particular, we expected faith factors of an intrinsic nature
      would promote this decision. Two weeks pre-operatively, patients (mean age = 65
      years) were recruited for interviews. One hundred seventy-seven CABG patients
      completed the pre-operative and post-operative follow-up one month after surgery,
      while 96 offered information regarding their engagement in settling end-of-life
      affairs. Cardiac indicators were obtained from the computerized Society of
      Thoracic Surgeons' Adult Cardiac Database (STS). Multiple regression analyses
      revealed that private religiousness increased the likelihood of having engaged in
      end-of-life decision planning by nearly half again (OR = .1.47, 95% CI = 1.10,
      1.96, p < .05) and that experiencing reverence in secular contexts nearly doubled
      the likelihood (OR = .1.99, 95% CI = 1.16, 3.44, p < .05). The reduced likelihood
      of having made plans was observed among those who scored higher on experiencing
      reverence in religious contexts (OR = .44, 95% CI = .23, .87, p < .05) and among
      patients using petitionary prayer (OR = .21, 95% CI = .04, .98,p < .05). These
      effects manifested after controlling for age, impacted functioning, and number of
      diseased arteries. Therefore, faith factors appear to have independent but
      complex effects on end-of-life decision making in middle-aged and older cardiac
      patients.

PMID- 18624024
TI  - Cost effectiveness or quality of care?

PMID- 18624025
TI  - What do physicians think about physician assisted suicide and voluntary
      euthanasia?

PMID- 18624026
TI  - Do doctors have a future? Key messages from the medical professionalism
      roadshows.

PMID- 18624027
TI  - The role of specialist physicians in the commissioning of clinical services.

PMID- 18624028
TI  - National review of deaths among HIV-infected adults.
AB  - This review describes patterns of mortality among adults infected with HIV in the
      UK and assesses the contributions of late diagnosis of HIV infection and non-HIV
      related disease to such mortality. In total, 387 adults with HIV who died between
      1 October 2004 and 30 September 2005 after receiving care at 90 clinical centres
      in the UK were reviewed. Causes of death and scenarios accounting for death were
      measured. Of the 387 deaths, 218 (56.3%) were readily attributable to infection
      with HIV. Only 123 (31.8%) deaths were considered not directly related to HIV.
      Late diagnosis of HIV accounted for 24.0% of all deaths and 35.2% of HIV-related
      deaths. Infection with HIV remains the main cause of mortality among infected
      patients in the era of highly active antiretroviral therapy. Late diagnosis of
      infection with HIV may be the largest potentially remediable factor for HIV
      associated death.

PMID- 18624029
TI  - What is the place of thrombolysis in acute stroke? A review of the literature and
      a current perspective.
AB  - The global burden of stroke, the undisputed success of intravenous thrombolysis
      in the management of myocardial infarction and subsequent evidence from animal
      models of cerebral infarction have all fuelled intense interest in the potential
      role for thrombolytic agents in the acute management of stroke in clinical
      practice. Before any clinical treatment is introduced universally its safety and
      efficacy must be demonstrated in the routine clinical environment and not just
      within the ideal conditions of controlled clinical trials. Similarly, the cost
      effectiveness of a new treatment modality is an essential consideration before
      its use is promulgated. This paper reviews the current scientific evidence for
      thrombolysis in stroke with reference to issues of safety, efficacy and cost
      effectiveness.

PMID- 18624030
TI  - Primary percutaneous coronary intervention for acute ST elevation myocardial
      infarction--first year's experience of a tertiary referral centre in the UK.
AB  - This study evaluated the first year's experience of a large interventional centre
      in the UK after a primary percutaneous coronary intervention (PCI) programme that
      runs 24 hours a day and seven days a week was started. Workload, patient outcome,
      length of stay, and effect on the remainder of the interventional service were
      analysed. The primary PCI service for a mainly urban population of 800,000 was
      started in April 2005. All relevant characteristics, details of procedures,
      outcome, and other data on quality of care were collected and entered
      prospectively onto a computerised database. Data were analysed with SPSS (version
      13.0). Over a 12-month period, 305 patients were diagnosed with ST elevation
      myocardial infarction (STEMI), of whom 259 (85%) were accepted for primary PCI.
      Median door-to-balloon time was 98 minutes, which decreased from 106 minutes in
      the first six months to 93 minutes in the second six months (p < 0.005). In
      hospital mortality was 4.5% and 30-day mortality was 4.9%. Median length of stay
      was three days, which was reduced from the six days previously reported after
      thrombolysis. Waiting times for other acute and elective PCI procedures did not
      increase after initiation of the primary PCI programme. Primary PCI can be
      delivered successfully in a setting in the UK with low mortality and reduced
      length of stay and without a negative impact on other interventional services.

PMID- 18624031
TI  - Diagnosis and management of patients with heart failure in England.
AB  - The objective of this postal survey was to assess the services currently accessed
      by primary care trusts (PCTs) for patients with chronic heart failure. Of the 303
      PCTs in England, 225 (74%) responded to the questionnaire. Natriuretic peptides
      were used by 61 (26%) PCTs, whereas direct access to echocardiography was
      available to 163 (72%) and heart failure clinics to 95 (42%). Heart failure
      services were led by a cardiologist in 138 (61%) main referring hospitals, an
      elderly care physician in 33 (15%), and other physicians in 50 (22%). In total,
      138 (62%) PCTs had access to heart failure nurses and 40 (18%) used coronary
      heart disease nurses; in 13 (5%) PCTs, patients with heart failure were seen by
      practice nurses. This survey highlights the need for further research on the cost
      effectiveness of service models for diagnosing and managing heart failure. The
      evidence base behind heart failure nurses should support their wider
      availability. The question of who cares for patients with heart failure should be
      reflected more widely in specialist training programmes in both secondary and
      primary care.

PMID- 18624032
TI  - Pathogenesis of HIV: non-specific immune hyperactivity and its implications for
      vaccines.
AB  - More than a decade ago, the pathogenesis of AIDS was reviewed in this journal,
      using the subtitle 'classical and alternative views', when evidence was
      accumulating that HIV could not cause AIDS simply through direct cytopathic
      mechanisms alone. Generalised immune activation after infection with HIV is now
      understood to be associated with and predictive of disease progression and
      probably represents the single most important difference between rapid
      progression and slow or non-progression. However, the fundamental source of this
      phenomenon remains undetermined. Do pathogenic events after acute infection
      promote an environment susceptible to increased hyperactivity or does inherent
      reactivity towards HIV in susceptible individuals ultimately influence these
      processes? New strategies aimed at eliminating HIV-induced immune activation are
      required, as is investigation into the clinical and immunological influence of
      antibodies that target HIV epitopes associated with disease and that are not
      necessarily neutralising. Therapeutic vaccines to prevent disease may be more
      practical and effective than classic prophylactic vaccination.

PMID- 18624033
TI  - The New Zealand national junior doctors' strike: implications for the provision
      of acute hospital medical services.
AB  - The New Zealand junior doctors' strike provided an opportunity to consider
      strategies that might be employed to overcome the international shortage of
      junior doctors. This article reports the experience of the emergency department
      (ED) and internal medicine (IM) services at Wellington Hospital during the
      national strike, in which medical services were primarily provided by specialist
      consultants in addition to, or as part of, their routine work. During the strike,
      elective admissions and outpatient clinics were mostly cancelled. In the ED, the
      waiting times and length of stay were markedly reduced. In IM, the proportion of
      patients admitted to the short stay unit rather than the general medical wards
      increased. Notwithstanding the different work circumstances, in both services one
      senior doctor carried the workload of at least two junior doctors. The deployment
      of additional senior medical staff to acute hospital services could greatly
      reduce the total number of doctors required. This strategy would have
      implications in terms of supporting acute medicine specialty initiatives,
      training, quality of care and funding.

PMID- 18624034
TI  - The concept, delivery and future of medical ambulatory care.
AB  - Bed shortages, efficient modern diagnostic services and increasing risks
      associated with hospital admission, require review of conventional medical
      practice. Patients referred as emergencies who are walking, talking sense, eating
      and drinking and have normal sphincter function can usually be managed as
      outpatients. Widespread adoption of this practice would require more general
      physicians and nurse practitioners near the front door, rapid access and early
      review clinics and prompt diagnostic support. Education of the public, changes in
      medical training and reallocation of resources would reduce the need for
      inpatient management, providing beds for those in real need.

PMID- 18624035
TI  - The new EU health strategy: a step forward or another example of 'bureaucracy
      total control'?
AB  - This article sets out the background to and the aims of the European Union (EU)
      health strategy published by the European Commission in October 2007. It explains
      the rationale for EU action in health, including the need to ensure effective
      cooperation in protection of health, and outlines the main principles and
      objectives of the strategy. Finally, it emphasises the need to implement the
      strategic goals by close cooperation with the member states and the important
      role for health professions and civil society.

PMID- 18624036
TI  - International medical graduates: lessons from the past and hopes for the future.
AB  - The high levels of unemployment among international medical graduates (IMGs) in
      the UK and the skewed career structure of the NHS may stem from the 1930
      withdrawal of General Medical Council recognition for Indian degrees forcing
      Indian colleges to align more closely with Western medical practices. From 2001
      emigration to the UK surged just when UK medical schools were increasing their
      output. The result was severe unemployment among IMGs. The visa restrictions put
      in place to correct this make it difficult for IMGs to come to the UK even for
      short periods of experience. However, the Medical Training Initiative visa
      category offers an alternative and allows them the opportunity to gain up to two
      years' UK experience. The NHS has been in debt to IMGs and the countries that
      trained them since its inception. We must look for new ways to maintain
      international links and for the NHS to play a positive role in the global health
      economy.

PMID- 18624037
TI  - Respiratory problems on the acute take: pleural disease and acute dyspnoea.
AB  - Respiratory disease contributes significantly to the workload of the acute
      medical take. This article, aimed at all physicians, reviews the evidence base
      for common respiratory conditions presenting as an acute emergency. There is
      particular emphasis on pleural disease and respiratory diagnoses likely to
      present with acute breathlessness.

PMID- 18624038
TI  - Paediatric gastroenterology 1966-2000.
AB  - Between 1966 and 2000 the pattern of gastroenterological disease in children in
      developed communities changed. Clinically severe infective gastroenteritis has
      declined in incidence. Infection of children with the conventional serotypes of
      Escherichia coli dramatically declined. During this period many new infective
      agents notably rota virus were recognised. By contrast, more children with
      chronic inflammatory bowel disease (IBD), especially Crohn's disease, have been
      diagnosed than ever before. Gastrointestinal allergy is increasingly recognised
      but the pattern of disease has changed. Technological advance in accurate
      diagnosis occurred with an emphasis upon tissue diagnosis. Introduction to
      clinical practice of ileocolonoscopy in the late 1970s immensely increased the
      ability to make the diagnosis of chronic IBD in children. Therapeutic advance has
      seen development of parenteral nutrition and enteral feeding as major therapies
      for children. In the UK there has been a rise and fall in university departments
      of paediatric gastroenterology.

PMID- 18624039
TI  - Oral rehydration therapy: applied physiology.

PMID- 18624040
TI  - Inflammatory bowel disease in children.

PMID- 18624041
TI  - Pathogenesis of gastrointestinal infection.
AB  - The last 30 years has seen the recognition of many intestinal pathogens, through
      a combination of microscopy, tissue availability and open minds. In the
      developing world the challenge to eradicate such infections continues, especially
      in infancy and early childhood. In developed communities, however, the challenge
      is shifting to pathogens ('super bugs') arising from our own interventions and
      lifestyles which will occupy many future careers.

PMID- 18624042
TI  - Working with schools in deprived areas to raise aspirations for medicine and
      other healthcare science careers.
AB  - Educational attainment is inversely related to socio-economic status. The
      achievement gap widens as children progress through the system. Take up of
      science options is particularly poor and difficulties are compounded by lack of
      relevant science-based work experience in deprived areas. The interaction of
      these factors is examined in some detail in an area of socio-economic
      deprivation. High attainment in sciences is usually considered a core requirement
      for acceptance into medicine and widening access to medicine for school leavers
      is therefore very difficult in these circumstances. A partnership between
      hospitals and local schools, including science-based work placements, is
      described. Cooperation between the NHS and schools by provision of work
      experience and teaching materials could help to address these issues as well as
      potential staffing difficulties in other healthcare science careers in the
      future. Expenditure can be justified on the grounds of known links between
      health, education and employment.

PMID- 18624043
TI  - Do musicians have different brains?
AB  - The search for anatomical correlates of special skills dates from the end of the
      19th century, when post-mortem brains of gifted individuals, including musicians,
      were examined for clues as to origins of their prized abilities. Modern
      neuroimaging techniques provide the chance to interrogate the brains of living
      musicians. Structural and functional specialisations have been demonstrated
      across several sensory, motor and higher order association areas. These
      specialisations are often instrument- or effector-specific and correlate with
      aspects of the training history supporting the view that they are the result,
      rather than the cause, of skill acquisition. Musicians constitute a model, par
      excellence, for studying the role of experience in sculpting brain processes. A
      key challenge for the future will be to develop theoretical frameworks within
      which musicians and other occupationally specialised groups can be studied in
      order to investigate the nature, scope and limits of neuroplasticity.

PMID- 18624044
TI  - The centenary of Garrod's Croonian lectures.
AB  - Archibald Garrod's Croonian lectures, Inborn errors of metabolism, were delivered
      at the Royal College of Physicians in June 1908. Although their significance
      remained dormant for many years, and is still not fully appreciated, they are now
      recognised as the foundation of medical genetics.

PMID- 18624045
TI  - Falls and bone health: improving the quality of care.

PMID- 18624046
TI  - HIV and cardiovascular risk.

PMID- 18624047
TI  - HIV and postexposure prophylaxis.

PMID- 18624048
TI  - HIV transmission and sexually transmitted infections.

PMID- 18624049
TI  - Lymphogranuloma venereum: what does the clinician need to know?

PMID- 18624050
TI  - Syphilis: an update.

PMID- 18624051
TI  - Medication adherence in heart failure.
AB  - Barriers to successful medication adherence exist and poor adherence is common.
      Recurrent admission with chronic conditions should prompt a detailed enquiry into
      medication adherence.

PMID- 18624052
TI  - On the good use of epilepsy by Fedor Dostoevskii.

PMID- 18624053
TI  - Professor Sir Raymond 'Bill' Hoffenberg: a celebration and thanksgiving.

PMID- 18624054
TI  - Junior doctors' working hours: 48 hours in 2009. Meeting the challenge.

PMID- 18624055
TI  - Junior doctors' working hours (2).

PMID- 18624056
TI  - Junior doctors' working hours: a view from across the pond (3).

PMID- 18624057
TI  - Never say die?

PMID- 18624058
TI  - Lesson of the month (1).

PMID- 18624059
TI  - Lesson of the month (2).

PMID- 18624060
TI  - Sepsis accounts for half of early warning score triggers.

PMID- 18624061
TI  - An opportunity missed: tax alcohol itself.

PMID- 18624062
TI  - Restricted licensing for DVM graduates?

PMID- 18624063
TI  - An ethicist's commentary on the reproductively unsound bull.

PMID- 18624064
TI  - Dry foods and risk of disease in cats.

PMID- 18624065
TI  - Surgical approaches for cesarean section in cattle.
AB  - Bovine practitioners are often presented with dystocias that require a cesarean
      section. Many practitioners perform this surgery using the same approach each
      time due to their comfort with one specific approach or lack of familiarity of
      other available options. The goal of this article is to explain the advantages,
      disadvantages, and indications for each of the different approaches to aid the
      practitioner in achieving better surgical success rate.

PMID- 18624066
TI  - Estimate of the direct production losses in Canadian dairy herds with subclinical
      Mycobacterium avium subspecies paratuberculosis infection.
AB  - The objective of this study was to estimate the annual losses from Mycobacterium
      avium subspecies paratuberculosis (MAP) for an average, MAP-seropositive,
      Canadian dairy herd. A partial-budget simulation model was developed with 4
      components of direct production losses (decreased milk production, premature
      voluntary culling, mortality, and reproductive losses). Input values were
      obtained primarily from a national seroprevalence survey of 373 Canadian dairy
      farms in 8 of 10 provinces. The model took into account the variability and
      uncertainty of the required input values; consequently, it produced probability
      distributions of the estimated losses. For an average Canadian dairy herd with
      12.7% of 61 cows seropositive for MAP, the mean loss was $2992 (95% C.I., $143 to
      $9741) annually, or $49 per cow per year. Additional culling, decreased milk
      production, mortality, and reproductive losses accounted for 46%, 9%, 16%, and
      29% of the losses, respectively. Canadian dairy producers should use best
      management practices to reduce these substantial annual losses.

PMID- 18624067
TI  - Fatal dog attacks in Canada, 1990-2007.
AB  - In Canada, public debates on dog attacks are dominated by studies from the United
      States. An electronic search of media reports in the Canadian Newsstand database,
      for the years 1990 to 2007, identified 28 fatalities from dog-bite injuries.
      Predominant factors in this case series were owned, known dogs; residential
      location; children's unsupervised access to area with dogs; and rural/remote
      areas, including aboriginal reserves in the prairies. A higher proportion of sled
      dogs and, possibly, mixed-breed dogs in Canada than in the United States caused
      fatalities, as did multiple dogs rather than single dogs. Free-roaming dog packs,
      reported only from rural communities, caused most on-reserve fatalities. Future
      studies are needed to assess if this rural/urban divide is observed in nonfatal
      attacks and if the breeds that bite in Canada are different from the breeds that
      killed. Breed representation in this paper and, perhaps, multiple-dog
      overrepresentation should be understood in the context of the overall Canadian
      dog population.

PMID- 18624068
TI  - Clinical peripheral neuropathy associated with diabetes mellitus in 3 dogs.
AB  - Clinical and electrodiagnostic findings in 3 spontaneously diabetic dogs with
      clinical peripheral neuropathy (PN) are reported. Clinical signs of a PN may
      develop in diabetic dogs with adequate glycemic control. In addition, laryngeal
      paralysis may develop in association with diabetes mellitus in dogs with clinical
      PN.

PMID- 18624069
TI  - Palatal sclerotherapy: a potentially useful treatment of intermittent dorsal
      displacement of the soft palate in juvenile standardbred racehorses.
AB  - This study was aimed at evaluating the tolerability and the efficacy of palatal
      sclerotherapy in juvenile standardbred racehorses with easily audible "snoring
      like" respiratory noises suspected to be the result of intermittent dorsal
      displacement of the soft palate. The palate of 8 horses was injected with sodium
      tetradecyl sulfate under videoendoscopic guidance. Palatal sclerotherapy resulted
      in resolution of the respiratory noise in 7 horses, improvement of performance in
      6 horses, and mild side effects in only 3 horses. This preliminary study suggests
      that palatal sclerotherapy is a safe, repeatable, inexpensive, and promising
      technique that should be considered as an alternative to existing treatments of
      intermittent dorsal displacement of the soft palate.

PMID- 18624070
TI  - A survey for infection with Dirofilaria immitis, Ehrlichia canis, Borrelia
      burgdorferi, and Babesia canis in feral and client-owned dogs in the Turks and
      Caicos Islands, British West Indies.
AB  - The frequency of infection with Dirofilaria immitis and Babesia canis and
      seropositivity to Ehrlichia canis and Borrelia burgdorferi in feral and client
      owned dogs was determined. Feral dogs were 14.8 and 11.2 times more likely to be
      seropositive to D. immitis and E. canis, respectively, than were client-owned
      dogs. None of the dogs tested positive for B. burgdorferi or B. canis.

PMID- 18624071
TI  - Tracheal rupture in a cat: diagnosis by computed tomography.
AB  - A cat was presented with a history of worsening generalized subcutaneous
      emphysema following dental prophylaxis. Tentative diagnosis of tracheal rupture
      was made. The location and extent of the tear was confirmed with the help of
      computed tomography. This is the 1st computed tomographic description of tracheal
      rupture in the veterinary literature.

PMID- 18624072
TI  - Polioencephalomalacia in a llama.
AB  - A 5-year-old, female llama (Lama glama) developed acute, progressive neurological
      disease, characterized by recumbency, muscle fasciculations, intermittent
      convulsions/opisthotonos, and absent menace responses. Postmortem histopathologic
      lesions, limited to the cerebral cortex, consisted of necrosis of the superficial
      and deep laminae. The clinical disease and microscopic lesions were consistent
      with polioencephalomalacia.

PMID- 18624073
TI  - The other side of public relations.

PMID- 18624074
TI  - 2007 Meeting of the American College of Veterinary Surgeons.

PMID- 18624075
TI  - Emerging issues of pay-for-performance in health care.

PMID- 18624076
TI  - Financial gains and risks in pay-for-performance bonus algorithms.
AB  - Considerable attention has been given to evidence-based process indicators
      associated with quality of care, while much less attention has been given to the
      structure and key parameters of the various pay-for-performance (P4P) bonus and
      penalty arrangements using such measures. In this article we develop a general
      model of quality payment arrangements and discuss the advantages and
      disadvantages of the key parameters. We then conduct simulation analyses of four
      general P4P payment algorithms by varying seven parameters, including indicator
      weights, indicator intercorrelation, degree of uncertainty regarding intervention
      effectiveness, and initial baseline rates. Bonuses averaged over several
      indicators appear insensitive to weighting, correlation, and the number of
      indicators. The bonuses are sensitive to disease manager perceptions of
      intervention effectiveness, facing challenging targets, and the use of actual-to
      target quality levels versus rates of improvement over baseline.

PMID- 18624077
TI  - Medicare physician group practice demonstration design: quality and efficiency
      pay-for-performance.
AB  - The Medicare Physician Group Practice (PGP) demonstration is Medicare's first
      physician pay-for-performance (P4P) initiative. The demonstration, which is
      legislatively mandated, establishes incentives for quality improvement (QI) and
      cost efficiency at the level of the PGP Ten large physician groups are
      participating in the demonstration, which started on April 1, 2005, and will run
      for 3 years. In this article the authors provide an overview of the PGP
      demonstration's key design elements, including the selection process for PGP
      participants; beneficiary assignment; comparison population; measurement of
      demonstration savings; performance payments; and quality measurement and
      reporting. A summary of early case study findings is also provided.

PMID- 18624078
TI  - Profiling efficiency and quality of physician organizations in Medicare.
AB  - This article presents a methodology for profiling the cost efficiency and quality
      of care of physician organizations (POs). The method is implemented for the
      Boston metropolitan area using 2002 Medicare claims. After adjustments for case
      mix and other factors, 4 of 30 organizations are identified with different than
      average efficiency Twenty-one of 30 organizations are identified with a different
      composite quality of care than average. Without changes in PO behavior, the gains
      from redirecting patients from lower to higher efficiency and quality providers
      are likely to be limited.

PMID- 18624079
TI  - Hospital size, uncertainty, and pay-for-performance.
AB  - We construct statistical models to assess whether hospital size will impact the
      ability to identify "true" hospital ranks in pay-for-performance (P4P) programs.
      We use Bayesian hierarchical models to estimate the uncertainty associated with
      the ranking of hospitals by their raw composite score values for three medical
      conditions: acute myocardial infarction (AMI), heart failure (HF), and community
      acquired pneumonia (PN). The results indicate a dramatic inverse relationship
      between the size of the hospital and its expected range of ranking positions for
      its true or stabilized mean rank. The smallest hospitals among the augmented
      dataset would likely experience five to seven times more uncertainty concerning
      their true ranks.

PMID- 18624080
TI  - Pioneering pay-for-quality: lessons from the rewarding results demonstrations.
AB  - This article reports six overarching lessons learned from seven pioneering
      initiatives in the pay-for-quality (P4Q) movement. These lessons relate to the
      specific design and implementation challenges sponsors of P4Q programs can
      expect. The lessons are: (1) P4Q can prioritize providers' quality goals, (2)
      provider engagement is difficult, (3) P4Q escalates concerns for data accuracy
      and validity, (4) P4Q increases the need for population-based information
      technology and infrastructure, (5) tradeoffs exist between stimulating investment
      in quality infrastructure and diluting the power of incentives for individuals,
      and (6) significant challenges exist in documenting a positive return on
      investment.

PMID- 18624081
TI  - Medicaid and SCHIP coverage: findings from California and North Carolina.
AB  - This article examines experiences under Medicaid and the State Children's Health
      Insurance Program (SCHIP), drawing on surveys of over 3,000 enrollees in
      California and North Carolina in 2002. In both States, Medicaid enrollees were
      less likely than SCHIP enrollees to have parents who were covered by employer
      sponsored insurance (ESI). With the exception of dental care and provider
      perceptions, access experiences were fairly comparable across the two programs,
      despite differences in the characteristics of the children served by the two
      programs. Relative to being uninsured, Medicaid enrollment was found to improve
      access to care along a number of different dimensions, controlling for other
      factors. Furthermore, this study emphasizes the need for continued evaluation of
      access to care for both programs.

PMID- 18624082
TI  - Medicare beneficiary knowledge of and experience with prescription drug cards.
AB  - Medicare beneficiaries used prescription drug discount cards, both Medicare and
      non-Medicare cards, to assist them in paying for the cost of prescription drugs.
      This article describes the beneficiary's awareness and understanding, sources of
      information, and experience with drug discount cards a year prior and during the
      implementation of the Medicare-Approved Prescription Drug Discount Card program.
      Also, it explores beneficiary characteristics that contribute to card ownership
      and knowledge about drug discount cards. Understanding these experiences and
      factors can inform future outreach and education campaigns for the Medicare Drug
      Coverage program.

PMID- 18624083
TI  - Impact of drug coverage on medical expenditures among the elderly.
AB  - Our study compares expenditures for Medicare covered medical services among
      enrollees in three State pharmacy assistance programs with spending among low
      income residents eligible or near-eligible for, but not enrolled in such State
      sponsored programs after controlling for between-group differences in
      demographic, socioeconomic, health status, and insurance status characteristics.
      We estimate a two-part model in total and by type of service (inpatient,
      outpatient, and professional) and chronic condition (hypertension, heart disease,
      and arthritis). We find that drug coverage has no discernible effect on the use
      and cost of inpatient services, but is associated with a statistically
      significant increase in Medicare spending for physician services.

PMID- 18624084
TI  - Prescription drug coverage among Medicare beneficiaries.
AB  - The Medicare Current Beneficiary Survey (MCBS) is a longitudinal survey of a
      nationally-representative sample of Medicare enrollees. The survey collects
      information on a variety of topics, including beneficiaries' health status;
      health care use and financing; and social, economic, and demographic
      characteristics. Medicare administrative data is regularly coupled with the
      information collected through the survey for validation purposes.

PMID- 18624085
TI  - Recent advances in the treatment of intimate partner violence and abuse.
      Foreword.

PMID- 18624086
TI  - State standards for domestic violence perpetrator treatment: current status,
      trends, and recommendations.
AB  - We empirically surveyed and analyzed existing standards for the treatment of
      perpetrators of domestic violence across the United States. Specific areas
      examined included: presence and scope; administrative entity for certifying;
      screening and risk assessment protocols; minimum length of treatment; theoretical
      or conceptual orientation; treatment content; preferred or allowable modalities
      of treatment; whether research findings are mentioned; methods for revising
      standards; and minimum education and training required for providers. We examined
      trends using several methods including comparisons between present and previous
      survey data (Maiuro et al., 2001). Positive trends were evident including
      increased use of multivariate models of treatment content, use of an intake
      assessment prior to treatment, use of a danger/lethality assessment to manage
      risk, recognition of the need for program evaluation and supportive research, and
      the requirement of a minimum level of formal education as a prerequisite for
      providers. We identify specific areas for further research and development and
      make recommendations for improving existing practice and standards of care.

PMID- 18624087
TI  - Group interventions for men who batter: a summary of program descriptions and
      research.
AB  - This article provides a summary of the latest research on men's group
      interventions for men who batter their intimate partners. The major components of
      current programs are described, along with studies on treatment effectiveness.
      Evidence for the effectiveness of treatment combined with a coordinated community
      response is also presented. Several related topics are covered, in particular
      methods for enhancing treatment motivation and culturally competent practice.

PMID- 18624088
TI  - Individual treatment of intimate partner violence perpetrators.
AB  - This article outlines a rationale for investigating the individual (one-on-one)
      treatment format and individualized (case-tailored) services for partner abuse
      perpetrators. Many state standards caution against or prohibit individual
      services in abuser intervention. However, initial research indicates that
      motivational interviewing, conducted individually, can increase abusive clients'
      engagement in the change process. Challenges of using the group format in
      treatment development are discussed along with potential benefits of individual
      treatment for this population. Notably, individual treatment can be adapted to
      the client's stage of change, can address a range of presenting concerns (such as
      substance abuse and mood disorders) that may influence outcome, and can be used
      to focus clinical attention on case-specific change targets while avoiding
      potentially negative and antisocial peer influences in the group format.
      Nevertheless, individual treatment has been almost entirely ignored to date in
      clinical research with this population.

PMID- 18624089
TI  - Couples treatment for interpersonal violence: a review of outcome research
      literature and current clinical practices.
AB  - Conjoint couples treatment for interpersonal partner violence (IPV) remains
      controversial despite a growing body of research and practice experience
      indicating that it can be effective and safe. In addition, developing typologies
      of couples who are violent suggest that a "one-size-fits-all" treatment approach
      to IPV is not appropriate and conjoint treatment may have a place in the
      treatment of at least some couples. In this article, we review the experimental
      studies and clinical practices of conjoint treatment. Based on this review, we
      suggest current best practices for this approach to treatment. Best practices
      include couples treatment as part of a larger community response to IPV, careful
      screening of couples for inclusion in couples treatment, modification of typical
      conjoint approaches to promote safety and ongoing assessment of safety with
      contingency plans for increased risk.

PMID- 18624090
TI  - Intimate partner violence risk assessment and management.
AB  - While risk assessment is important in the management of intimate partner violence
      perpetrators, the science and practice of risk assessment in this field are still
      in early development. This article reviews the literature on intimate partner
      violence risk assessment. The original intent was to direct discussion to assist
      the Military Family Advocacy Program (FAP), U.S. Department of Defense, to
      develop guidelines for the treatment of domestic violence offenders. The article
      is divided into sections as follows: (a) Defining Risk; (b) The Risk Factors; (c)
      Models of Risk Assessment; (d) Existing Risk Instruments; (e) The Role of the
      Victim in Risk Assessment; (f) Qualifications to Conduct Assessments; (g)
      Communicating Risk; and (h) Managing Risk. Relevant issues and controversies are
      raised throughout the article.

PMID- 18624091
TI  - Child abuse in the context of domestic violence: prevalence, explanations, and
      practice implications.
AB  - This article addresses the following questions: (a) How common is child abuse
      among domestically violent families? (b) Are there specific patterns of child
      abuse among domestically violent families? (c) What may explain occurrences of
      child abuse in domestically violent families? (d) How might domestic violence
      affect treatment for child abuse? We review research on child abuse in the
      context of domestic violence. We discuss implications of this research for
      service-delivery programs for domestically violent families.

PMID- 18624092
TI  - Substance abuse by men in partner abuse intervention programs: current issues and
      promising trends.
AB  - This article discusses key studies linking intervention for co-occurring
      substance abuse and partner abuse. Findings are grouped into three areas: (a) the
      effect of addictions treatment on partner violence; (b) application of
      transtheoretical, motivational, and culturally focused approaches to improve
      engagement and prevent attrition; and (c) assessment-based matching of services.
      Finally, the relative value of serial, coordinated, and integrated substance
      abuse programs and partner abuse intervention programs are considered. We reached
      three primary conclusions: (a) Addiction treatment alone reduces the risk for
      future domestic violence in a subset of men who batter, (b) screening and
      assessment for substance abuse by all men in partner abuse intervention programs
      is a standard of practice but needs to extend beyond "intake" and occur
      periodically, and (c) coordinated and integrated substance abuse and domestic
      violence programs probably offer more safety than traditional serial substance
      abuse treatment followed by partner abuse intervention.

PMID- 18624093
TI  - A framework for treating partner aggressive women.
AB  - Women are increasingly referred to intervention programs to address their use of
      physical violence against intimate partners. This article reviews the scant
      treatment outcome and attrition literature for partner aggressive women and
      describes important characteristics of partner aggressive women that must be
      taken into consideration in designing treatment. Recommended treatment modules
      are described in detail and include skill-building to enhance safety planning,
      conflict management, emotional regulation, communication and negotiation, and
      stress management. Additional modules should be included for some women based on
      individualized needs. These may include parenting skills and education and
      referral for treatment of conditions that undermine emotional stability, such as
      posttraumatic stress symptoms, substance abuse, and mood disorders. Treatment
      structure is outlined and pragmatic issues regarding the implementation of
      treatment are discussed. Interventions for partner aggressive woman must be
      designed to address women's victimization experiences as well as their
      perpetration.

PMID- 18624094
TI  - Explaining antigay violence using target congruence: an application of revised
      routine activities theory.
AB  - This research examines predictors of antigay violence (physical assault, sexual
      assault, and property damage) using Finkelhor and Asdigian's (1996) revised
      routine activities theory, which predicts that target congruence increases
      victimization risk. Results indicate about half of the sample experienced at
      least one type of victimization, while 25% experienced two or more types.
      Physical violence was the most common type of antigay victimization, with
      property damage and sexual assault occurring less often. Having a higher level of
      contact with gay/lesbian organizations and being out of the closet or open about
      sexual orientation increases the risk of both physical assault and property
      damage. More frequent drinking to intoxication also increases the risk of antigay
      motivated physical assault. The sexual assault model was not significant.
      Implications for future research and prevention are discussed.

PMID- 18624095
TI  - The significance of the victim advocate for domestic violence victims in
      municipal court.
AB  - Previous research has examined factors that influence felony case prosecution in
      domestic violence cases, but few have analyzed how victim participation, or lack
      thereof, may affect the defendant's case outcome in misdemeanors. This study used
      384 municipal cases from a specialized domestic violence court to examine the
      role of the victim advocate and variables that had an impact on victim
      participation with prosecution and case disposition. To ensure that decisions in
      all cases were consistent, all decision makers in the sample involved the same
      group: the court advocate, prosecutor, and judge. The analysis found that victim
      cooperation after arrest coupled with services provided by shelter court
      advocates were a strong predictor of victim cooperation at disposition and case
      outcome.

PMID- 18624097
TI  - Women's risk for revictimization by a new abusive partner: for what should we be
      looking?
AB  - The purpose of this article was to examine the prevalence of, as well as risk
      factors for, revictimization by a new partner. Data was collected via face-to
      face interviews at Time 1 (about 5 weeks after obtaining a protective order
      against a violent partner [DVO partner]) and at Time 2 (approximately 12 months
      later). Of those women who reported having a new partner at Time 2 (n = 412),
      35.2% reported abuse. Findings indicate that there is a subset of women who are
      at greater risk of experiencing abuse by future partners: women with greater
      cumulative lifetime victimization and those who abuse or are dependent on illicit
      drugs. Intervening with women when they obtain a protective order is a critical
      point of intervention to reduce women's risk for revictimization.

PMID- 18624096
TI  - A review of research on women's use of violence with male intimate partners.
AB  - This article provides a review of research literature on women who use violence
      with intimate partners. The central purpose is to inform service providers in the
      military and civilian communities who work with domestically violent women. The
      major points of this review are as follows: (a) women's violence usually occurs
      in the context of violence against them by their male partners; (b) in general,
      women and men perpetrate equivalent levels of physical and psychological
      aggression, but evidence suggests that men perpetrate sexual abuse, coercive
      control, and stalking more frequently than women and that women also are much
      more frequently injured during domestic violence incidents; (c) women and men are
      equally likely to initiate physical violence in relationships involving less
      serious "situational couple violence," and in relationships in which serious and
      very violent "intimate terrorism" occurs, men are much more likely to be
      perpetrators and women victims; (d) women's physical violence is more likely than
      men's violence to be motivated by self-defense and fear, whereas men's physical
      violence is more likely than women's to be driven by control motives; (e) studies
      of couples in mutually violent relationships find more negative effects for women
      than for men; and (f) because of the many differences in behaviors and
      motivations between women's and men's violence, interventions based on male
      models of partner violence are likely not effective for many women.

PMID- 18624098
TI  - Female sex offenders' relationship experiences.
AB  - Interventions for child sexual abusers should take into account their
      perspectives on the context of their offenses, but no descriptions of everyday
      life from the offender's point of view have been published. This study therefore
      explored female offenders' views of their strengths and challenges. Documented
      risk assessments of 20 female offenders were analyzed using inductive content
      analysis (Cavanagh, 1997; Priest, Roberts, & Woods, 2002; Woods, Priest, &
      Roberts, 2002). The Good Lives Model provided the initial coding framework and
      ATLAS.ti software (Muhr, 1997) was used for simultaneous data collection and
      analysis. The content analysis yielded 999 coding decisions organized in three
      themes. The global theme was relationship experiences. Offenders described the
      quality of their relationship experiences, including their personal perspectives,
      intimate relationships, and social lives. These descriptions have implications
      for treatment planning and future research with women who have molested children.

PMID- 18624099
TI  - Correlates of partner abuse in male same-sex relationships.
AB  - We investigated correlates of partner abuse in male same-sex relationships in a
      randomly selected community sample (N = 186). We included factors associated with
      abuse in heterosexual relationships, as well as factors of relevance to gay
      relationships. We assessed perpetration and receipt of partner abuse to examine
      whether variables were associated independently with abuse perpetration and/or
      receipt. Correlates of same-sex partner abuse were largely parallel to
      established correlates of heterosexual abuse. Income, education, and attachment
      orientation were associated with bidirectional partner abuse, and family violence
      and substance use were uniquely associated with victimization. Further, there
      were factors unique to same-sex partner abuse; HIV status and public outness were
      associated with bidirectional partner abuse, and internalized homophobia was
      uniquely associated with abuse perpetration.

PMID- 18624100
TI  - The relationship between childhood abuse and suicidality in adult bipolar
      disorder.
AB  - This study evaluates the effect of childhood sexual and physical abuse on
      suicidality in adults with bipolar disorder. We conducted a retrospective chart
      review of adult outpatients (N= 381) with DSM-IV-TR-defined bipolar disorder
      seeking evaluation and treatment at an academic specialty research program (i.e.,
      Mood Disorders Pharmacology Unit, University Health Network, University of
      Toronto) between October 2002 and November 2005. Eighteen percent (n = 68) of
      adult patients with bipolar disorder had a recorded history of childhood abuse (p
      = 0.009). Sixty-three percent (n = 43) of bipolar patients with a history of
      childhood abuse reported lifetime suicidality (chi2 = 6.885, df= 1, p = 0.009).
      Logistic regression analysis indicated that Childhood abuse was a significant
      predictor of lifetime suicidality in adult bipolar patients (OR = 2.05, CI = 1.19
      3.510). Childhood abuse is associated with suicidal ideation and suicide attempts
      in adults with bipolar disorder. Anamnestic inquiry regarding childhood
      maltreatment is salient to risk assessment, illness management planning,
      preventative strategies, and treatment interventions in bipolar disorder.

PMID- 18624101
TI  - Rape myths among Appalachian college students.
AB  - Rape myths regularly admonish victims for supposedly provoking the violence done
      against them. While rape attitudes have been studied in national and urban
      samples, the support of rape myths in rural populations is seldom investigated.
      Furthermore, the few empirical studies on sexual coercion in Appalachia are
      mostly descriptive and rarely compare the sentiments of Appalachians and non
      Appalachians. To address this gap, this study surveyed 512 college students at a
      public university in Eastern Kentucky. In testing an Appalachian distinctiveness
      question, this study revealed that Appalachian students were less likely to
      criticize rape victims. Students were also less inclined to condemn rape victims
      when they were victims themselves, came from egalitarian families, stayed in
      college longer, rejected modem sexism, and felt little animosity toward women.

PMID- 18624103
TI  - Alert: change in compliance expectations for emergency management standards.

PMID- 18624102
TI  - Understanding intimate partner violence against women in the rural South.
AB  - Most U.S. intimate partner violence (IPV) research to date has been limited to
      women residing in urban areas, with the small body of research focusing on rural
      populations being primarily qualitative. In this case-control study of Southern
      rural women, while many factors are consistent with those found in urban
      settings, unlike findings elsewhere, IPV risk appears to increase with age, and
      race showed no increased risk. Furthermore, in rural areas where guns are more
      acceptable than in other parts of the United States, partners of IPV victims are
      considerably more likely to carry weapons than partners of nonabused women. Given
      the geographic limitations to police and medical response to severe IPV in a
      rural setting, an improved understanding of IPV risk among this population can
      aid health care providers in ascertaining risk before it escalates further.

PMID- 18624104
TI  - Approved: adverse event reporting for New York office-based surgery practices.

PMID- 18624105
TI  - Approved: requirement for accredited nursing homes to notify the Joint Commission
      when they become a special focus facility.

PMID- 18624106
TI  - The Joint Commission's latest report provides tool to assess and overcome
      language, cultural barriers.

PMID- 18624107
TI  - ["Hand-foot" syndrome--after liposomal pegylated doxorubicin in patients with the
      ovarian cancer recurrence (own experiences)].
AB  - AIM: To present our own experience with pegylated liposomal doxorubicin applied
      in ovarian cancer patients. MATERIAL AND METHODS: The group of 32 patients with
      ovarian cancer was treated with pegylated liposomal doxorubicin (LPD) in Klinika
      Onkologii Klinicznej Centrum Onkologii Branch Gliwice between the years 2004 and
      2007. Median age was 47 years. The histoclinical variables potentially
      influencing the occurrence of the hand-foot syndrome were analyzed. RESULTS: Hand
      foot syndrome has been observed in 11 patients (34.4%) treated with the LPD. The
      lesions have been present on the skin of hands, feet, elbow and knee joints and
      armpits. In the analyzed group of patients, the risk of the hand-foot syndrome
      occurrence increased, however non-significantly, with the increase of number of
      cycles including LPD (p=0.069) and the number of previous lines of chemotherapy
      (p=0.067). Other analyzed factors had no negative influence on the hand-foot
      syndrome occurrence. CONCLUSIONS: It is important to inform the patients about
      the risk of the hand-foot syndrome occurrence and its management. Early diagnosis
      allows to prevent the worsening of the hand-foot syndrome and makes it possible
      to continue the chemotherapy without the necessity of dose reduction and breaking
      from the therapy.

PMID- 18624108
TI  - [The diagnostic value of chosen questionnaires (UDI 6SF, Gaudenz, MESA, ICIQ-SF
      and King's Health Questionnaire) in diagnosis of different types of women's
      urinary incontinence].
AB  - THE AIM: The assessment of the usefulness of the following questionnaires: UDI
      6SF, King's Health Questionnaire, Gaudenz, MESA, ICIQ-SF in diagnosis of
      different types of women's urinary incontinence. MATERIAL AND METHODS: The study
      included 100 women who were hospitalized in the Department of Urology of St.
      Rafael Hospital in Czerwona Gora due to urinary incontinence. On the basis of the
      received data we have compared the data from questionnairies to the results of
      the urodynamic study. RESULTS: The mean age of women was 55.6 years. The stress
      urinary incontinence (SUI) was diagnosed in 32%, urgent urinary incontinence
      (UUI) in 10% and mixed urinary incontinence (MUI) in 55% of women, and neurogenic
      bladder in 3%. The data obtained from the study showed that questionnaires had
      98% sensitivity and 50% specificity in diagnosing the type of urinary
      incontinence in women. CONCLUSIONS: 1. Data obtained from the questionnaires
      fails to offer enough information to make a certain diagnosis of urinary
      incontinence. 2. The questionnaires: ICIQ-SF, Gaudenz and MESA are effective in
      the diagnosis of mixed urinary incontinence. 3. In spite of their high
      sensitivity, the specificity of questionnaires in the diagnosis of urinary
      incontinence is rather low.

PMID- 18624109
TI  - [Assesment of real optoelectronic method in the detection of cervical
      intraepithelial neoplasia].
AB  - INTRODUCTION: Biophysics is becoming an important factor in prevention of
      cervical cancer. One of the most promising concepts of biophysical program for
      the prevention of cervical cancer is the optoelectronic method--Truscreen.
      OBJECTIVE: The objective of the work was to determine the usefulness of the real
      optoelectronic device in the detection of cervical intraepithelial neoplasia
      MATERIAL AND METHOD: From August 2006 till September 2007, 147 patients were
      examined in the Laboratory of Pathophysiology of Uterine Cervix in Gynecology and
      Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical
      Sciences. The study reports prospective, blind trial. The following diagnostic
      examinations were carried out: examination with the use of optoelectronic method,
      DNA HPV HIGH RISK test, colposcopy examination and histopatologic biopsy.
      RESULTS: The specificity of the optoelectronic method for positive diagnoses
      amounted to 84%. The sensitivity for intraephitelial changes (CIN 1, CIN 2) was
      estimated at 53%, and for severe grades (CIN 3, Carcinoma planoepitheliale) at
      80%. CONCLUSIONS: Optoelectronic diagnostics is useful in the detection of
      cervical neoplastic changes. The optoelectronic method may prove to be a
      significant diagnostic device at the basic and advanced level of cervical
      screening. The advantage of the optoelectronic method over prevention based on
      cytodiagnostics and colposcopy, includes the immediate result of the examination
      and its automation as well as standardization.

PMID- 18624110
TI  - [Fetal echocardiography in fetal ovarian cysts].
AB  - OBJECTIVES: The aim of the study was to evaluate the outcome of fetuses with
      ovarian cysts in relation to fetal echocardiography. MATERIAL AND METHODS: In the
      Department for Diagnosis and Prophylaxis of Birth Defects at the Polish Mother's
      Memorial Hospital in Lodz fetal echocardiography was performed in 21 fetuses with
      ovarian cysts between the years 1995-2006. OUTCOMES: In 18 out of 21 (86%)
      fetuses we have found normal heart anatomy (NHA) and in 3 fetuses congenital
      heart defect (CHD). In 7 out of 18 (39%) fetuses with NHA there were functional
      anomalies, including 5 fetuses with hypertrophy Four neonates with hypertrophy
      required surgical procedures after the delivery. Prenatal hypertrophy was not
      observed in case of only one neonate which was operated after the delivery.
      CONCLUSIONS: 1. Fetal echocardiography studies were very often abnormal in fetus
      with ovarian cysts (mainly as functional anomalies). 2. Functional anomalies
      detected in fetal echocardiography more often resulted in surgical procedures
      after the birth, whereas normal heart study was more often connected with
      spontaneous regression of ovarian cyst (p=0.0265).

PMID- 18624111
TI  - [Influence of parity on the body mass of neonates].
AB  - OBJECTIVES: The purpose of the study was to determine whether there exists a
      positive correlation between the mother's parity and the child's weight on
      delivery. MATERIALS AND METHODS: A retrospective study has been conducted on a
      selected group of 86 multiriparas with three deliveries. Only in term babies of
      healthy mothers were taken into consideration. Data derived from cases has been
      analyzed by means of Microsoft Excel and Statistica 6.0 software. RESULTS: In
      65.1% of the cases, the birth weight of the second neonate exceeded the weight of
      the first one. The rate diminishes to 51.2% when we compare the third child with
      the second. In 2.3% of the records no changes have been observed. The
      abovementioned criteria enabled us to form three groups out of the initial cohort
      and perform further analysis. CONCLUSIONS: Significant correlation between birth
      weight of the first and second newborn has been found. No such correlation was
      found in the case of the second compared to the third delivery.

PMID- 18624112
TI  - [The (-2548G/A) polymorphism of leptin gene in women with gestational
      hypertension and preeclampsia].
AB  - INTRODUCTION: Leptin is a polypeptide hormone (167 amino acids, molecular weight
      of about 16kDa), synthesized mainly in white adipose tissue. The hormone plays an
      important role in regulation of hunger and satiety processes, in metabolism of
      carbohydrates and fats, development of cardio-vascular diseases and obesity. The
      occurrence of the increased level of leptin in pregnant women with hypertension,
      especially in women with preeclampsia, has also been brought to our attention. In
      recent years it has been suggested that the presence of different variants of
      leptin and leptin receptor genes may modify the leptin level in serum, and, in
      this way, influence an increased risk of obstetric complications, such as
      preeclampsia or eclampsia. MATERIALS AND METHODS: We have analyzed a group of 103
      hypertensive pregnant women--61 women with gestational hypertension (GH) and 42
      women with preeclampsia (PE). The control group consisted of 113 healthy pregnant
      women who have been investigated. Gestational hypertension and preeclampsia were
      recognized with the help of and assessed according to the ACOG criteria. The (
      2548G/A) polymorphism was determined using polymerase chain reaction/restriction
      fragment length polymorphism (PCR/RFLP). RESULTS: In our study, a higher
      frequency of mutated AA genotype in GH group and PE groups (21.31% and 21.43%
      respectively vs. 16.81% in the controls) and the overrepresentation of mutated A
      allele in both analyzed groups (47.54% and 45.24% respectively vs. 41.59% in the
      controls) have been observed, without statistically significant differences.
      CONCLUSIONS: The overrepresentation of AA genotypes and higher frequency of
      mutated A allele of (-2548G/A) polymorphism of leptin gene in GH and PE groups
      might indicate its possible contribution in gestational hypertension and
      preeclampsia.

PMID- 18624113
TI  - [Rho kinase--a new target for pharmacological treatment of an overactive
      bladder].
AB  - Rho kinase plays a key role in the regulation of smooth muscles contraction,
      including those of the urinary bladder detrusor. Rho kinase pathway modulates the
      level of phosphorylation of the myosin light chain, mainly through the inhibition
      of myosin phosphatase. Recent experimental data indicate that its role might be
      exacerbated in local and systemic pathological conditions which affect the
      bladder. It seems that Rho kinase inhibitors, such as Y27632, may turn out to be
      an effective group of drugs in pharmacotheraphy of an overactive bladder (OAB),
      which will influence the storage phase of the micturition cycle, without
      interfering with the physiological voiding.

PMID- 18624114
TI  - Three classes of pelvic and aortic lymphadenectomy in patients with cervical
      cancer.
AB  - Currently, the extent of pelvic and aortic lymphadenectomy is currently described
      by numerous and ambiguous terms. The aim of this study is to present a
      classification of pelvic and aortic lymphadenectomy in cervical cancer patients.
      On the base of the data from the literature, pelvic and aortic lymphadenectomies
      have been assigned to three different classes, depending on surgical technique,
      the extent of the lymphadenectomy and the specificity of the removed lymph node
      groups. Class I equals removal of selected lymph nodes; Class II: removal of
      lymph nodes situated ventrally and laterally to large extraperitoneal vessels and
      the obturator nerve and of lymph nodes situated ventrally and laterally to the
      aorta and vena cava; Class III: total removal of lymphatic tissue around the
      iliac vessels and from the obturator fossa dorsally to the obturator nerve and
      from the presacral region and lymphatic tissue around the aorta and vena cava.
      The presented classification allows for a unequivocal assessment of pelvic and
      aortic lymphadenectomy.

PMID- 18624115
TI  - The diagnostic problems in patient with ascites, elevated Ca 125 level and
      autoantibodies against nuclear antigens and smooth muscle antigens mimicking
      advanced ovarian carcinoma--case study.
AB  - The paper describes a case of 26-year-old patient primarily suspected to suffer
      from the ovarian or peritoneum cancer due to high level of Ca 125 antigen and
      ascites. During exploratory laparotomy, neoplastic process was excluded, which
      was confirmed by histopathological examination. Further diagnostic tests were
      performed. The patient was not infected with hepatitic B or C virus, and there
      was no biochemical evidence of liver disease. Detailed, wide biochemical and
      immunological investigations detected antinuclear and anti smooth muscle
      autoantibodies in the blood serum. Afterwards, the patient was admitted to the
      Department of Gastroenterology and autoimmune chronic hepatitis was confirmed.

PMID- 18624116
TI  - [Polish Gynecological Society's recommendations regarding cesarean section].

PMID- 18624117
TI  - [The plasma level of sL-selectin, myeloperoxidase and granulocyte-colony
      stimulating factor (G-CSF) in breast cancer patients in the course of
      chemotherapy].
AB  - Neutrophils kill tumor cells through mechanisms of cell cytotoxicity, dependent
      on myeloperoxidase. The proliferation and activity of mature granulocytes are
      stimulated by the granulocyte--colony stimulating factor (G-CSF). The purpose of
      this investigation was to evaluate the level of adhesion molecule--sL-selectin,
      as a measure of mature granulocyte activity and myeloperoxidase responsible for
      their cytotoxicity. Additionally we have investigated the plasma level of G-CSF
      which can increase in the breast cancer. We tested 15 patients with III stage
      breast cancer and 18 patients with IV stage. Plasma samples were drawn before and
      in the course (12th week) of chemotherapy. The control group consisted of 10
      healthy women. The plasma levels of sL-selectin, myeloperoxidase and G-CSF were
      measured using a sensitive sandwich ELISA system. In breast cancer patients (III
      and IV stage) before and in the course of chemotherapy sL-selectin concentration
      was decreased, but myeloperoxidase concentration increased in comparison to the
      control group. The level of sL-selectin and myeloperoxidase in the 12th week was
      decreased when compared to the level before chemotherapy. These results suggest
      that levels of tested parameters do not correlate with G-CSF concentration.

PMID- 18624118
TI  - [Prenatal diagnosis of fetal chromosomal aneuploidies using quantitative
      fluorescent PCR (QF-PCR)].
AB  - The trisomy of the 21 chromosomes is one of the most important chromosomal
      anomalies and is responsible for Down syndrome. It persists in Poland in 1/700
      birth. The risk of childbirth with Down syndrome grows with age, especially in
      women after 35 years old. In this study we performed QF-PCR method with specific
      polymorphic sequence--D21S11 for detection of trisomy of the 21 chromosome. DNA
      for PCR was isolated from amniotic fluid, blood of healthy and with Down syndrome
      patients. PCR was performed with ProfilerPlus Kit, which permits for
      amplification of 9 STR loci (also D21S11) and gender marker--amelogenin gene. We
      detected incorrect amplification of STR sequence for D21S11 in one amniotic
      fluid, which was confirmed by kariotyping as trisomy of the 21 chromosome of
      fetus.

PMID- 18624119
TI  - [Pathologies of the cervical spine anatomy as a possible cause of young patients
      vertigo].
AB  - Vertigo occurs in many diseases, especially in older people. It is a specific
      diagnostic problem in young people. In the paper, 86 young patients with
      incidental vertigo were clinically assessed. Electronystagmography, eye-tracking
      pattern test, optokinetic test and cervical spine X rays were used in
      examination. The results were compared with the control group of young and
      healthy people and also with the older patients group with degenerative changes
      of the cervical spine. In the examined group the disturbances of physiologic
      cervical lordosis were found in 33.8% and positional nystagmus in 23%. The
      vestibular tests and hearing were frequently normal. These results suggest that
      disturbances of physiologic cervical lordosis may be the cause of balance
      disturbances.

PMID- 18624120
TI  - [Metabolic syndrome in young adults type 1 diabetic patients].
AB  - AIM: The aim of the study was to estimate the prevalence of metabolic syndrome
      (MS) in type 1 diabetic patients and to assess the relationship between the
      scores of MS components and body mass and metabolic control. MATERIAL AND
      METHODS: 165 patients aged 18-32 years with diabetes duration 8-26 years were
      included into the study. The height, weight, waist circumference and blood
      pressure were measured. HbA1c and plasma lipids concentrations were examined.
      Body mass index (BMI), waist/hip ratio (WHR) and daily dose of insulin were
      calculated. MS was diagnosed according to the definition of National Cholesterol
      Education Program (NCEP) Adult Treatment Panel III (ATP) and International
      Diabetes Federation (IDF). RESULTS: The prevalence of individual components of MS
      was 10.3% for high triglycerides, 7.3% for low HDL, 27.9% for high blood
      pressure, and 10.3% for abnormal waist circumference according to NGEP and 18.8%
      according to IDF definition. After assuming that all type 1 diabetic patients
      fulfilled criteria for hyperglycemia, the prevalence of MS diagnosed according to
      NCEP was 10.9% (95% CI 6.1-15.7) and according to IDF was the same 10.9% (95% CI
      6.1-15.7). In 14 patients MS was diagnosed according to both definitions, whereas
      4 met only the NCEP, and another 4 met only the IDF criteria. Rrelationships
      between the scores of MS components and BMI (p < 0.0001) and HbA1c (p = 0.002)
      were found. Patients with MS were older than the patients without MS (p = 0.003)
      and needed higher insulin doses (p = 0.028). CONCLUSIONS: According to the NCEP
      and IDF criteria similar prevalence of MS is recognized in type 1 diabetic
      patients. Only in 2/3 of them MS is diagnosed according to both definitions. The
      most frequently occurring component of MS is elevated blood pressure. The scores
      of MS components are related to the presence of overweight and to poor metabolic
      control.

PMID- 18624121
TI  - [Ceramides and adhesive molecules in stable ischaemic heart disease].
AB  - The aim of the study was assessment of plasma level of ceramides and adhesive
      molecules in patients with stable ischaemic heart disease (IHD). Ischaemic heart
      disease was verified by coronary angiography as a 1.2 or 3 vessels disease. The
      study based on 35 patients (11F, 24 M,aged 40-74 yrs). The control group
      consisted of 16 healthy persons (5F, 11M, aged 43-66 yrs). Fasting plasma was
      drown to asses levels of ceramides, the soluble forms of E-selectin and
      intercellular adhesive molecule-1 (ICAM-1) and total cholesterol, chol-HDL, chol
      LDL and triglicerides. Decreased concentrations of ceramides with mono- and
      polyunsaturated fatty acids were observed in patients with stable IHD. In 3
      vessels disease the total level of ceramides was higher than in 1 vessel disease
      (p < 0.05). The plasma concentration of sE-selectin, ssICAM-1 were elevated in
      patients compared to control group (p < 0.02 and p < 0.05, respectively). The
      plasma levels of sICAM-1 were significantly higher in 3 vessels disease than in 1
      vessel disease (p < 0.01). Ceramides concentration with saturated fatty acids
      correlated with adhesive molecules (p < 0.05). A negative correlation was
      observed between sICAM-1 concentration and ceramides with palmitoleic acid or
      docosahexaenoic acid (p < 0.05).

PMID- 18624122
TI  - [Role of amylin in glucose homeostasis and its perspective use in diabetes
      management].
AB  - In response to hyperglycemia, beta-cells release insulin and C-peptide, as well
      as islet amyloid pancreatic polypeptide - amylin. In diabetgic patients beta-cell
      destruction does not only result in deficiency of insulin, but also a deficiency
      of C-peptide and amylin. Amylin is clearly involved in glucose homeostasis
      through the inhibition of gastric emptying and postprandial hepatic glucose
      production, eventually reducing postprandial glucose excursions. Most recently,
      the synthetic amylin analog pramlintide was shown to improve glycemic control in
      diabetic patients. Amylin replacement with pramlintide as an adjunct to insulin
      therapy is a novel physiological approach toward improved long-term glycemic and
      weight control in patients with type 1 and type 2 diabetes.

PMID- 18624123
TI  - [Coexistance of autoimmunological diseases with type 1 diabetes mellitus in young
      patients based on literature and own experience].
AB  - Patients with autoimmune type 1 diabetes mellitus have often, besides immune
      diabetic markers, also other organ-specific antibodies. In many diabetic patients
      autoimmune thyroid diseases, i.e. Hashimoto thyroiditis and Grave's disease, with
      silent clinical course can be diagnosed. Because 50% of children with diabetes
      and significant titres of thyroid autoantibodies (ATA) develop thyroid problems
      within 3-4 years, examinations of thyroid antibodies should be performed yearly.
      In cases of significant antibody titres, thyroid function tests and ultrasound
      assessment are recommended in order to minimize the risk of undiagnosed
      hypothyroidism in these patients. Coeliac is an other disease commonly coexisting
      with type 1 diabetes mellitus and autoimmune thyroid diseases. It is recommended
      that screening for coeliac disease should be part of the routine investigation
      for all patients. Potential benefits of treatment coeliac disease is more
      prevalent in individuals with type 1 diabetes mellitus, and when untreated is
      associated with a number of medical complications, including poor glycaemic
      control. Identification of patients with coeliac has been facilitated in recent
      years by serological screening. Initial normal screening does not exclude coeliac
      and repeated screening is indicated, a positive IgA antibody test to tTG is a
      more sensitive parameter than EmA for silent coeliac disease in patients with
      diabetes. Confirmatory small bowel biopsy, however, remains necessary for
      diagnosis as some patients with positive antibodies may be without histological
      changes.

PMID- 18624124
TI  - [Psychic consequences of natural disasters].
AB  - The consequences of natural disasters were presented according to: development of
      the diagnosis of PTSD, variability of factors impacting on formation and
      sustenance (support) of distemper related to a cataclysm. The natural disaster
      causing emotional sufferings might be also the reason of psychic distempers that
      led to: 1. real or anticipate fear of death, 2. physical injuries, 3. economic
      loss, or 4. death of the relatives. Occurrence of PTSD relies on the pre
      traumatic factors (like sex, coexistence of psychic disaster and/or risk of any
      other traumatic disturbances in the past, economical status, education), on the
      sort, intensity and duration of keeping the disorders initiated by the stressor
      and on the posttraumatic features such as social and psychological support.

PMID- 18624125
TI  - [Glossopharyngeal neuralgia with MAS syndrome and complex partial seizures].
AB  - The authors present a 56-year-old-man with idiopathic glossopharyngeal neuralgia,
      complicated by cardiac disturbance with asystole and complex partial seizures.
      The mechanism of epileptic seizures was released due to transient brain
      ischaemia, which was caused by cardiac disturbance with asystole, during pain
      episodes. Pacemarker implantation completely abolished cardiac disturbance and
      complex partial seizures.

PMID- 18624126
TI  - [Synchronous squamous vulvar and cervical cancer--a case report with literature
      review and analysis of therapeutic strategies].
AB  - We report on a suboptimal surgical treated cancer of the vulva with the
      accidental diagnosis of a second cancer within the completion of the surgery
      three weeks later. The patient was 48 years old, presenting with a central,
      multifocal, exophytic tumor of the clitoris. The primary surgery was: vulvectomy
      with bilateral inguinal lymphadenectomy ("triple incision"). However, the
      pathological examination revealed an unsatisfactory surgical result--on the one
      site (laterally) the tumor reached the resection edge, and on the other site
      (dorsally) the tumor-free margin was only 1-2 mm. There were 5 nodal metastases-
      4 ipsilateral (one macrometastasis), and 1-contralateral. The next step was total
      abdominal hysterectomy (co-existing 10cm myoma) and pelvic lymph node sampling
      (on both sites negative). We discuss two problems in light of the current
      literature: the preoperative therapy planning of advanced vulvar cancer
      (exenteration vs. neoadjuvant chemotherapy with subsequent radical vulvectomy,
      triple incision vs. en bloc resection, pelvic lymphadenectomy) and the importance
      of a careful evaluation of the cervix in each case of vulvar cancer--the
      coincidence of both tumor localizations is up to 7-10%. The diagnosis of the
      second cancer probably remains in many cases delayed.

PMID- 18624127
TI  - [Vertebral arteries dissection as a rare cause of central nervous system
      ischemia].
AB  - However rare, dissection of extracranial cerebral arteries is one of the most
      often causes of ischemic stroke in young people. Early diagnosis and treatment
      promote artery recanalization that results in total symptom regression. The
      proper diagnosis is in many cases is difficult. The reason is the variety of
      causative factors, clinical symptoms and difficulty of direct dissected vertebral
      arteries visualisation in common Duplex-Doppler examination. In our article we
      present 3 causes of vertebral arteries dissection. We would like to call your
      attention to consider this causative factor in differentiation diagnostics of
      central nervous system ischemia. This complication may occur not only due to a
      communication accident, but also during playing tennis and bowling.

PMID- 18624128
TI  - Goal setting.
AB  - I would not tell any individual what his or her goals should be or what the
      picture of one's life should look like. I strongly believe in human potential,
      and I love to see people achieve more of the things that are important to them.
      The Goal Curves exercise is probably one of the most powerful methodologies used
      to help individuals get the most out of their lives while enjoying every day;
      this exercise leads to much greater individual success. However, for it to be
      effective, one needs to develop his or her goals and then review and act on them
      on a regular basis.

PMID- 18624129
TI  - Perioral soft-tissue rejuvenation techniques to enhance esthetic restorative
      dentistry.
AB  - Every practitioner has the obligation to offer his or her patients the latest
      advances in their profession. Dentistry has made a shift over the past 50 years
      from caries restoration and prosthetic replacement to preventative and esthetic
      rejuvenation. Related dental specialties have also blossomed with new procedures
      and an expanded scope of practice. This shift has also included more
      comprehensive care and treatment of the oral and maxillofacial region. Modern
      esthetic dentists realize the facial soft tissues serve as a frame for their
      restorative artwork. Contemporary oral and maxillofacial surgery includes
      cosmetic facial surgery. Procedures for such surgery are taught in oral and
      maxillofacial surgery residency programs, are part of the oral and maxillofacial
      surgery board exams, and are covered by oral and maxillofacial surgery
      malpractice companies. Esthetic dentists should understand facial aging, as well
      as the basic procedures available for facial rejuvenation by the oral and
      maxillofacial surgeon. Contemporary esthetic dentistry goes beyond the oral
      cavity, and the smile is truly enhanced by simultaneous facial rejuvenation. This
      article discusses the process of perioral facial aging and various cosmetic
      facial surgery options.

PMID- 18624130
TI  - Evidence-based nonsurgical periodontal therapy.

PMID- 18624131
TI  - Why wavelength and delivery systems are the most important factors in using a
      dental hard-tissue laser: a literature review.
AB  - Various lasers have been investigated in the dental clinic as an alternative to
      the dental drill for the treatment of dental hard tissues. Among the lasers, the
      erbium-based solid-state infrared lasers, operating at approximately 3 microm,
      have demonstrated they are effective in dental applications because of their high
      affinity for water in the hydroxyapatite of the tooth structure. Water is the
      dominant chromophore that absorbs the laser energy during hard-tissue treatment;
      this leads to well-established, mechanical, thermally driven, and explosive
      ablation, which is the basis for the erbium laser-tissue interaction. A review of
      the literature presents a number of studies in which the superior qualities of
      the Er:YAG laser, in particular, are demonstrated. Er:YAG irradiation results in
      the least amount of temperature increase at the laser-tooth interface. The Er:YAG
      laser generates photons with the strongest absorption by water in the enamel and
      dentin and, when combined with a water cooling spray, produces extremely minor
      zones of carbonization, debris, and necrosis after irradiation. Furthermore, the
      Er:YAG laser wavelength can be easily delivered with a hollow waveguide delivery
      system and contact sapphire tip, resulting in a more precise cavity preparation
      than other delivery systems. The Er:YAG laser system offers the optimal
      wavelength and the ability to be transmitted in the most efficient manner for
      successful dental hard-tissue ablation.

PMID- 18624132
TI  - Nickel-titanium usage and breakage: an update.

PMID- 18624133
TI  - Reducing reproductive rights:spousal consent for abortion and sterilisation.

PMID- 18624134
TI  - Binayak Sen: redefining health care in an unjust society.

PMID- 18624135
TI  - AIDS vaccine trials for India: getting the facts right.

PMID- 18624137
TI  - A review of the ethics in research on child abuse.
AB  - Research on violence and abuse, particularly involving vulnerable groups such as
      women and children, has many ethical ramifications. There are few published
      reports in India on ethical guidelines and standards in this area. This paper
      reviews Child Abuse: India 2007, a study conducted by the ministry of women and
      child development, government of India. The review highlights the need for
      conducting an ethical inquiry in this area. Certain concerns about the conduct of
      the study are raised. Core ethical issues pertaining to consent and refusal, risk
      and benefit, effects of the study process on the researcher and the researched
      and the reporting of adverse events are discussed. The ethical implications of
      the study and ethical responsibilities of the researcher are emphasised.

PMID- 18624138
TI  - Medical negligence and the law.
AB  - After the Consumer Protection Act, 1986, came into effect, a number of patients
      have filed cases against doctors. This article presents a summary of legal
      decisions related to medical negligence: what constitutes negligence in civil and
      criminal law, and what is required to prove it.

PMID- 18624139
TI  - Discrepancies in the laws on identifying foetal sex and terminating a pregnancy
      in India.
AB  - Laws that regulate the identification of a foetus and the termination of a
      pregnancy in India are shaped by their social context. The Medical Termination of
      Pregnancy Act, 1971, discriminates against unmarried women by not recognising
      that unwanted pregnancies in unmarried women could result in at least as much
      anguish and suffering as that experienced by married women. While the MTP Act
      permits the abortion of foetuses with disabilities, the Pre-conception and Pre
      natal Diagnostic Techniques (Prohibition of Sex Selection) Act's ban on
      identifying the foetus's sex prevents the use of sex-detection to identify
      foetuses at high risk of sex-linked diseases.

PMID- 18624140
TI  - Lessons from the recently halted microbicide trial in India.

PMID- 18624141
TI  - ICMR guidelines on assisted reproductive technology: lacking in vision, wrapped
      in red tape.

PMID- 18624142
TI  - Waiting for the doctor...

PMID- 18624143
TI  - On the other side of the waiting room.

PMID- 18624144
TI  - The dynamics of efficiency.

PMID- 18624145
TI  - Awareness of issues related to torture among medical students in Mauritius.
AB  - Torture in custody is a global problem. Many declarations and conventions by
      different agencies throughout the world have sought to address this issue. Health
      professionals are required to detect, treat, and rehabilitate victims of torture.
      In the last few years, medical personnel have emphasised their stand against the
      practice of torture. We surveyed 155 second- and third-year medical graduates in
      Mauritius to assess their knowledge of and attitudes towards torture. A majority
      of the students have a basic awareness and would like to learn more about torture
      as a human rights issue. However, more than 37 per cent of students were in
      favour of beating in custody. Torture could be reduced if the medical profession
      maintains high standards of practice and ethics. Medical education for the
      prevention of torture should be included in the undergraduate medical curriculum.

PMID- 18624146
TI  - Emerging issues in genetic testing in Sri Lanka.

PMID- 18624147
TI  - The ethics of rationing antiretroviral treatment.

PMID- 18624148
TI  - Sex imbalances in kidney transplants in Iran.

PMID- 18624149
TI  - Unpaid hospital bills.

PMID- 18624150
TI  - Mass culling for avian influenza: rational strategy or needless destruction?

PMID- 18624151
TI  - Budget 2008 and health care: less of the same?

PMID- 18624152
TI  - Notification of transfusion transmitted infection.
AB  - The National Blood Policy of India, 2002, advocates the disclosure of results of
      transfusion transmitted infections (TTI) to blood donors. However, in the absence
      of well-defined notification processes, and in order to avoid serious
      consequences resulting from unguided disclosure, blood bank personnel discard
      blood that is TTI-positive. We report on a survey of 105 voluntary blood donors
      in Kerala. Only two out of three participants had filled the donor form in the
      last year. Only half were aware that the blood bank was supposed to inform them
      if they tested positive for TTI. Fifty-seven per cent of donors wanted to be
      informed every time they donated blood, irrespective of a positive or negative
      result.

PMID- 18624153
TI  - The impact of TRIPS on innovation and exports: a case study of the pharmaceutical
      industry in India.
AB  - Currently, there is a debate on what impact the implementation of the Trade
      Related Aspects of Intellectual Property Rights (TRIPS) in India would have on
      its pharmaceutical industry and health care. The debate hinges primarily on two
      major questions. First, will the new patent regime provide an impetus for
      innovation in the pharmaceutical industry? Second, how far will India's
      pharmaceutical exports of copied versions of patented drugs to developing
      countries be restricted under the new regime? The first question seeks to find
      out if TRIPS will increase India's innovative capabilities to fill the current
      vacuum to develop drugs for tropical diseases. The large multinational companies
      (MNCs) that dominate the global pharmaceutical industry have no interest in
      commercial ventures that have little potential for great returns on investment.
      The second question attempts to find a solution to the lack of access to medicine
      in most developing countries. Indian manufacturers' supply of reverse-engineered
      drugs, which cost only a fraction of the prices charged by MNCs, may be coming to
      an end under the new regime. Against this backdrop, this article attempts to
      analyse the impact of strengthening intellectual property rights in India.

PMID- 18624154
TI  - How TRIPS benefits Indian industry and how it may not benefit the Indian people.

PMID- 18624155
TI  - Should there be mandatory testing for HIV prior to marriage in India?
AB  - The National AIDS Prevention and Control Policy of the government of India states
      that testing for HIV infection should be voluntary in nature. But from time to
      time various state governments and the central government have announced their
      intent of introducing mandatory premarital testing. Though this intent has not
      yet been translated into action, we present our case against the adoption of such
      a policy by discussing various social and medical issues. These include the
      limited population that such a policy would target given the early age of
      marriage in India; issues related to its implementation considering the low
      marriage registration rates in India; potential of stigma and discrimination
      associated with it; issues with defining boundaries and the role of the state;
      limitations related to the HIV test itself in context of the policy, including
      the window period and the positive predictive value of the test; its limited
      impact in population groups at a high risk for HIV infection; its limited role in
      changing unsafe behaviours; its limited potential to enhance the empowerment of
      women; its conflict with existing human rights; and the adverse experience of
      other countries with a similar policy.

PMID- 18624156
TI  - Mental health services: indigenous models of care in the community.

PMID- 18624157
TI  - Obtaining informed consent and other ethical dilemmas.
AB  - In the extracts from the discussion presented below, Prof Macklin (RM) and Dr
      Guerrero-Cohen (DG-C) respond to researchers' queries. Some of the dilemmas that
      the researchers describe were faced in their own work. Others, based on questions
      raised by the institutional ethics committee of the Anusandhan Trust, were
      summarised from the IEC's report.

PMID- 18624158
TI  - Stem cell transplantation in India: tall claims, questionable ethics: a response.

PMID- 18624159
TI  - National bioethics conference: participants' comments.

PMID- 18624160
TI  - Adapting reinsurance to relieve biotech bottleneck.

PMID- 18624161
TI  - Plans don't applaud Healthy Americans Act.

PMID- 18624162
TI  - Statins continue to be ubiquitous, but increasingly controversial.

PMID- 18624163
TI  - Medicare to cut physician pay--maybe.

PMID- 18624164
TI  - During economic downturn, diversity relieves the pain.

PMID- 18624165
TI  - An evidence base for primary care. Interview by John Marcille.

PMID- 18624166
TI  - Smoking programs succeed for plans and patients.

PMID- 18624167
TI  - Clinical decision support on slow road to adoption.

PMID- 18624169
TI  - Academic detailing effectively reduces Rx costs.

PMID- 18624168
TI  - Health plan joins with physical therapy facility to manage back and neck pain.
AB  - Twenty-five billion dollars is spent each year on the medical care of back pain,
      and $50 billion is lost in productivity. Primary care physicians might have
      difficulty providing thorough counseling and treatment to their patients about
      the condition. In 2006, Capital Health Plan (CHP) partnered with Orthopedic and
      Sports Physical Therapy, which employed the mechanical diagnosis and therapy
      (MDT) technique. After undergoing this technique, members experienced a 79%
      improvement in pain scores and a 54% improvement in function scores, compared to
      when they started treatment.

PMID- 18624170
TI  - Kaiser's EMR push pays off.

PMID- 18624171
TI  - Prescription benefit costs rise less steeply.

PMID- 18624172
TI  - [Variation characteristics and controlling factors of heavy metals in the South
      Yellow Sea surface seawaters].
AB  - Based on the 8 cruises data of surface seawater heavy metals and other related
      environmental factors from 1997 to 2004 of the South Yellow Sea (SYS),
      distribution patterns, mechanisms controlling the distributions and pollution
      levels of heavy metals (As, Cd, Cu, Hg, Pb, Zn) were studied with the data of
      2003-10, and 8-year-fluctuation trends of heavy metals were also discussed. The
      average concentrations of heavy metals in surface seawater were 2.33, 0.078,
      1.41, 0.003 6, 0.37, 6.21 microg/L respectively. The average concentrations
      showed a relatively stable trend in 8 years, except Zn's distinct upward
      tendency. The distribution patterns corresponded to the distance away from the
      coastline,that was, the content of heavy metals (except Pb) was low in central
      area while high inshore. Those were responses of human activity in the marginal
      sea, however, in some local areas, Pb was controlled by atmospheric deposition,
      Cd was relative to pH and salinity, Hg was related to organic carbon, Cu and Zn
      were influenced by runoff and drainage, and the resuspending of sediments played
      important roles on the content and distribution of As. Compared to the Marine
      Water Quality Standard of China, heavy metals indicated that SYS was a first
      class sea, and Ecological Risk Index analysis showed that SYS was a low
      ecological risk sea. In conclusion, seawater quality of heavy metals in SYS
      surface seawater is relatively good in general.

PMID- 18624173
TI  - [Distribution characteristics of phthalic acid esters in the Wuhan section of the
      Yangtze River].
AB  - Samples of water and sediment were collected at 30 sites in Wuhan section of the
      Yangtze River in high and low water period. Phthalic acid esters (PAEs)
      concentrations in each sample were determined by Gas Chromatography. The results
      were shown as follows: (1) PAEs concentrations in water phase of lakes and
      tributaries ranged from 0.114-1.259 microg/L in high water period and 0.25-132.12
      microg/L in low water period, while slight increasing trends could be discovered
      in the main stream (0.034-0.456 microg/L and 35.73-91.22 microg/L in high and low
      water period, respectively). (2) PAEs concentrations in sediment phase of
      tributaries and lakes in low water period were from 6.3 to 478.9 microg/g. Di-n
      butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) both had strong
      trends from water to sediment phase, and the PAEs concentration ranges of the
      sediment phase in the main stream were 151.7-450.0 microg/g in high water period
      and 76.3-275.9 microg/g in low water period; DBP could transfer from sediment to
      water in high water period, while DEHP still had a potential for adsorption in
      low water period. (3) Among five studied PAEs compounds, DBP and DEHP were the
      main pollutants. According to the Surface Water Quality Criteria of China (GB
      3838-2002), the limit values of DBP and DEHP for drinking water sources were
      0.001 and 0.004 mg/L. All water samples in high water period were up to standard
      while the standard-exceeding sections accounted for 82.4% in low water period.
      (4) The PAEs pollution of the Wuhan section was similar to the Velino lake in
      Italy or the middle and lower stream of the Yellow River in China. However, PAEs
      concentrations in water phase of the Wuhan section in high water period were
      lower than most water bodies at home and abroad.

PMID- 18624174
TI  - [Analysis of microbial community of a Beijing simulator water distribution
      system].
AB  - Identification of compositions of the biofilm in a Beijing simulator water
      distribution system pipe networks by PCR and single strand conformation
      polymorphism (PCR-SSCP) technique and analysis of its heterotrophic bacterial by
      heterotrophic plate count (HPC) were performed. Results showed that when the
      water velocities were same, the count of heterotrophic bacterial on the
      zinficated steel wall was about five times of the PVC. On the other hand, when
      the pipe materials were zinficated steel, the count of heterotrophic bacterial in
      the deadwater pipe wall was about 1/5 of the 0.6 m/s region. The difference of
      the bacterial count maybe related to the smooth of the water pipe surface and the
      velocity of flow which affected the attachment of the microorganisms and the
      quantity of O2 and nourishment, respectively. Same SSCP electrophoresis profiles
      were observed between samples from different material pipes and water velocities.
      After sequencing and contrasting with the GenBank, the identity of three bands
      from the SSCP gel with Bacillus cereus (GenBank AB190077), Peudomonas sp. yged143
      (GenBank EF419342) and a unclassified bacteria, Bacterium UASWS0134 (GenBank
      DQ190347) were 100%, 99% and 94%, respectively. The sameness of the microbial
      community structure may be induced by the samples which were from the same
      simulator system and the sampling regions were near and the microorganisms could
      transform in these regions easily. The observed potential pathogens of Bacillus
      cereus and Peudomonas sp. should lead to a consideration of the microbiology
      safety of drinking water.

PMID- 18624175
TI  - [Detection of enteric pathogenic bacteria from surface waters by quantitative
      polymerase chain reaction (QPCR)].
AB  - A rapid quantitative polymerase chain reaction (QPCR) analysis method with
      universal primers was developed to detect cell densities of the enteric
      pathogenic bacteria from 5 surface water of Xi'an City for 4 months continuously.
      And the detection results by QPCR method were compared with counts of coliforms
      colony-forming units (CFU) determined by membrane filter (MF) analysis. The
      results showed that QPCR method had an estimated 94% confidence, and detection
      limit was 2.7 Escherichia coli cells per sample in undiluted DNA extracts. For
      five surface waters (N = 60), the geometric mean of pathogenic bacteria
      concentration determined by QPCR was 2.2-5 times of corresponding coliform CFU
      determined by MF analysis. Using QPCR analysis, these geometric means of
      pathogenic bacteria concentration ranged from 25 CCE/100 mL to 67 000 CCE/100 mL.
      Using MF culture analysis, coliforms ranged from 3 CFU/100 mL to 45 000 CFU/100
      mL. Regression analysis showed that there was a significant positive correlation
      between pathogenic bacteria determined by QPCR method and coliforms determined by
      MF method, the correlation coefficient (r) was 0.983.

PMID- 18624176
TI  - [Self-aggregation property of bacterial alginates extracted from aerobic
      granules].
AB  - To explore bacterial alginates role in aerobic granules' formation, the alginate
      was extracted from aerobic granules and identified. Its aggregation property in
      50 mg x L(-1) CaCl2 solution was investigated by the atomic force microscopy
      (AFM). Bacterial alginates amounted to 35.1% +/- 1.9% of granules' dry mass. With
      the concentration increased from 10 mg x L(-1) to 500 mg x L(-1) in 50 mg x L(-1)
      CaCl2, the extracted alginates tended to form ordered aggregations, with the
      shape changed from randomly distributed globules, to rod-like and flower-shaped
      aggregations, and finally to weblike networks due to their supramolecular self
      assembly property. The three dimensional alginate-metal gel is the structural
      polymer of aerobic granules, and the alginates-Ca2+ gel formation plays an
      important role in granules' formation and structure stabilization.

PMID- 18624177
TI  - [Characteristic of natural organic matter removal by ferric and aluminium
      coagulation].
AB  - Natural organic matter removal efficiency and characteristic by ferric chloride
      and aluminium sulphate were studied. Results showed that ferric chloride was
      effective in natural organic matter removal when coagulant dosage was higher than
      15 mg/L, while aluminium was effective at lower dosage. The TOC of water was
      reduced to 4.19 mg/L and 9 mg/L at a dosage of 10 mg/L for aluminium sulphate and
      ferric chloride respectively, while TOC was reduced to 2.44 mg/L and 1.69 mg/L at
      the dosage of 20 mg/L. Ferric chloride decreased pH sharply than aluminium
      sulphate which made hydrolysate more positive and attachable for natural organic
      matter. UV254 and SUVA results showed that ferric chloride removed more conjugate
      structure materials and unsaturated band contents than aluminium. Ferric chloride
      was more effective in reducing lower molecular weight organic matter and
      hydrophilic substances than aluminium, when the dosage of coagulant was 20 mg/L,
      the removal efficiency of relative molecular weight below 10 000 was 16.4% and
      6.1% respectively, while aluminum was more effective in high molecular weight
      matter removal than ferric chloride.

PMID- 18624178
TI  - [Influence of surface chemical properties and pore structure characteristics of
      activated carbon on the adsorption of nitrobenzene from aqueous solution].
AB  - Commercial activated carbon was treated by HNO3 oxidation and then subsequently
      heat treated under N2 atmosphere. Effect of surface chemical properties and pore
      structure on the adsorption performance of nitrobenzene was investigated. N2/77K
      adsorption isotherm and scanning electron microscopy (SEM) were used to
      characterize the pore structure and surface morphology of carbon. Boehm
      titration, Fourier transform infrared spectroscopy (FTIR), the point of zero
      charge (pH(PZC)) measurement and elemental analysis were used to characterize the
      surface properties. The results reveal that HNO3 oxidation can modify the surface
      chemical properties, increase the number of acidic surface oxygen-containing
      groups and has trivial effect on the pore structure of carbon. Further heat
      treatment can cause the decomposition of surface oxygen-containing groups, and
      increase the external surface area and the number of mesopores. Adsorption
      capacity of nitrobenzene on AC(NO-T), AC(raw) and AC(NO) was 1011.31, 483.09 and
      321.54 mg x g(-1), respectively. Larger external surface area and the number of
      meso-pores, together with the less acid surface oxygen-containing groups were the
      main reason for the larger adsorption capacity AC(NO-T).

PMID- 18624179
TI  - [Adsorption of humic acid onto aminated HMS].
AB  - The adsorption of humic acid onto hexagonal mesoporous silica(HMS) and surface
      aminated HMS was investigated. The simulation results using Freundlich model
      indicated that the surface amination of HMS led to an increase of adsorption
      constant from 0.56 to 105, reflecting markedly enhanced adsorption of humic acid
      upon surface amination. In addition, humic acid adsorption under acidic
      conditions was favored. Adsorbed humic acid molecules were found to be located in
      the mesopores of aminated HMS and the mesopores with relatively larger pore
      diameters were preferentially occupied. The kinetics of humic acid adsorption
      onto the aminated HMS could be well described by second order kinetics and the
      adsorption rate was mainly dominated by intrapore diffusion process.

PMID- 18624180
TI  - [Optimization of nitrate recirculation flow and external carbon dosage integrated
      control for A/O biological nitrogen removal process].
AB  - In order to improve A/O process denitrification efficiency, five integrated
      control strategies of nitrate recirculation flow and external carbon dosage for
      denitrification were proposed and evaluated using the COST/IWA simulation
      Benchmark. Results show that control strategy No.1 is the best integrated control
      strategies from both external carbon consumption, effluent quality, and the
      stability of controller. It comprises two feedback control loops: one is to
      determine the flow rate of external carbon source, keeping the nitrate
      concentration at the end of anoxic zone at a pre-specified level 2 mg/L, and the
      other is to adjust the flow rates of the nitrate recirculation to keep the
      nitrate concentration at the end of the aerobic zone at a pre-specified level
      based on the effluent quality (usually 8-12 mg/L). This strategy can guarantee
      highly effective use of anoxic denitrification capacity in the low-load
      condition, and meet effluent discharge standards through carbon dosage in the
      high-load condition.

PMID- 18624181
TI  - [Effects of influent C/N ratio on performance of UniFed SBR process].
AB  - The effects of 7 groups of different influent C/N ratio (2.75, 4.28, 5.7, 6.5,
      6.97, 8.08, 11.19) on the removal efficiencies of total nitrogen, phosphorus and
      COD as well as the sludge settling performance were investigated in a UniFed SBR
      lab-scale apparatus treating actual domestic wastewater. The results showed that
      when the C/N ratio was lower than 5.7, TN removal efficiency increased sharply as
      C/N ratio increased, from 43.6% of 2.75 to 80.84% of 5.7. Afterwards, TN removal
      efficiency increased very slowly as C/N ratio increased, because only TN removal
      efficiency caused by SND during aeration period could be enhanced. P removal
      efficiency increased as C/N ratio increased, because PAOs could get more organic
      carbon source from the influent to produce PHB and release PO4(3-), avoiding the
      adverse influence of NO(x)- on PO4(3-) release. The higher the C/N ratio, the
      more the quantities of P release and uptake, the quicker P uptake rate, the
      better P removal performance was. Regardless of the C/N ratio, excellent COD
      (average 93.15%) removal efficiencies were maintained throughout the experiment.
      When Influent C/N ratio was bigger than 6.97 and organic load exceeded 0.38
      kg/(kg x d), SVI rose quickly as C/N ratio increased. Non-silk bacteria sludge
      bulge appeared because of low DO and high organic load.

PMID- 18624182
TI  - [Innovative application of carbon tube aerated membranes to enhance anaerobic
      baffled reactor for wastewater treatment].
AB  - New type hybrid biological reactor was developed by initiating the carbon
      membrane aeration in ABR which was augmented with carbon aerated membranes to
      improve wastewater treatment by removing COD, NH4(+) -N and TN. The results
      showed that on the conditions of intra-membrane pressure of 0.025 MPa, HRT 24 h,
      influent COD 2000 mg/L, NH4(+) -N 50 mg/L, simultaneous nitrification and
      denitrification was happened, and COD and NH4(+) -N decreased from 156 mg/L, 36
      mg/L to 45 mg/L, 6 mg/L respectively after the membrane aeration with biofilm was
      initiated in the third compartment of ABR.TN removal reached 87.66%, and VFA and
      biogas was decreased by 77.12% and 30%, respectively.

PMID- 18624183
TI  - [Start-up of carbon tube membrane-aerated biofilm reactor for completely
      autotrophic nitrogen removal].
AB  - A laboratory-scale membrane-aerated biofilm bioreactor (MABR) equipped with
      nonwoven fabrics support around the gas-permeable carbon tube was developed for
      single-stage autotrophic nitrogen removal based on partial nitrification and
      anaerobic ammonium oxidization. Initially, the reactor was inoculated with
      nitrifying biomass. By decreasing the air pressure in the lumen of carbon tube
      step by step, We can obtain stable nitrite accumulation. Subsequently, the
      reactor was reinoculated with Anammox biomass to construct a quite stable biofilm
      system for completely autotrophic N removal. After 120 d of operation, 88.7% of
      NH4(+) -N removal rate, 48.65 mg/L of average TN in the effluent, 83.77% of
      maximal TN removal efficiency was achieved under the following conditions: air
      pressure of 0.015 MPa, HRT of 6 h, and influent NH4(+) -N of 200 mg/L +/- 10
      mg/L.

PMID- 18624184
TI  - [Performance of biological phosphorus removal in anaerobic pre-fermentation and
      intermittent aerated biofilm system treating domestic wastewater].
AB  - A fixed-film system composed of anaerobic biofilter and intermittent aerated
      biofilter (IABF) was developed for enhanced biological phosphorus removal (EBPR)
      in treatment of domestic wastewater. Influence of hydraulic, organic, and
      phosphorus loading on performance of the system was investigated in this study.
      The result indicates that the system is efficient for the removal of organic and
      P in the treatment. At a hydraulic retention time of the system of 23.3-4.6 h,
      the effluent concentration and reduction efficiency of TP and COD are 0.59 mg/L,
      68 mg/L in average and 85.2%, 73.6% in average, respectively. A stable
      performance of EBPR in the system is achieved with a good adaptability of
      fluctuations of the loadings. An innovative method instead of traditional
      backwashing was applied to remove P in biofilm from IABF. The use of the method
      improves P-uptake capacity in biofilm during long-term operation without wasting,
      which prolongs operation duration and reduces backwashing frequency in IABF. Pre
      fermentation of domestic wastewater in anaerobic biofilter increases
      concentration of volatile fatty acids in the influent of IABF.

PMID- 18624185
TI  - [Effect of organic compounds on the degradation of nitrobenzene in aqueous
      solution by catalytic ozonation].
AB  - We investigated the effects of organic compounds on the processes of ozonation
      alone and ceramic honeycomb-catalyzed ozonation for the degradation of
      nitrobenzene in aqueous solution, including formaldehyde, methanol, formic acid
      and dibutyl phthalate. The results indicated that degradation rate of ozonation
      alone and ceramic honeycomb-catalyzed ozonation decreased by 11.6% and 9.6% with
      the increase of the concentration of formaldehyde (0-12 mg x L(-1)). The
      degradation rates of the two processes both increased firstly and decreased
      subsequently with the increase of the concentration of methanol (0-16 mg x L(
      1)). The degradation rate of ozonation alone reached the climax at the
      concentration of methanol 2 mg x L(-1), and that of ceramic honeycomb-catalyzed
      ozonation reached the culmination at the concentration of methanol 4 mg x L(-1)
      under the same experimental condition. With the increase of the concentration of
      formic acid (0-8 mg x L(-1)), the degradation rates also increased firstly and
      decreased subsequently, and those of ozonation alone and ceramic honeycomb
      catalyzed ozonation reached the vertex, respectively, at the concentration of
      methanol 0.5 mg x L(-1) and 2 mg x L(-1). At the lower concentration, methanol
      and formic acid could accelerate the degradation of nitrobenzene, however, the
      reaction was retarded at higher concentrations of methanol and formic acid. The
      degradation rates of ozonation alone and ozonation/ceramic honeycomb both
      declined by 19.7% and 18.6% with the increase of the concentration of dibutyl
      phthalate (0-10 mg x L(-1)).

PMID- 18624186
TI  - [Degradation of diuron by persulfate oxidation activated by EDTA-ferrous ion in
      aqueous system].
AB  - The method of diuron [3-(3,4-dichlorophenyl)-1, 1-dimethylurea] degradation by
      persulfate oxidation activated by EDTA-ferrous ion in aqueous system was
      conducted. Based on both of the degradation performance and the operating costs,
      optimal reaction condition was proposed. Operating at K2S2O8 initial
      concentration 2.0 mmol x L(-1), Fe(II) initial concentration 1.0 mmol x L(-1),
      EDTA initial concentration 0.5 mmol x L(-1), reaction time 300 min and pH = 7.0,
      about 67.6% of 0.1 mmol x L(1) diuron was degradation. Hydroxyl radicals and
      sulfate radicals produced in the system were determined by molecular probes
      (ethanol and tert-butanol) methods. The degradation products of diuron were
      identified with LC/MS methods and the degradation pathways of diuron were
      discussed.

PMID- 18624188
TI  - [Electrochemically reductive dechlorination of chloroform in aqueous medium by
      codeposited palladium-nickel glassy carbon as cathode].
AB  - The electrochemical deposition behaviors of Pd-Ni bimetal on glassy carbon (GC)
      electrode were studied by means of cyclic voltammetry (CV) based on orthogonal
      experiments. CV results reveal that Pd-Ni bimetal shows larger hydrogen
      adsorption peak than that of single Pd or Ni. The mixture of Ni2+ and Pd2+ can
      get hydrogen adsorption peak of -24.83 mA at - 500 mV (vs Hg/Hg2SO4). Scanning
      Electron Microscope (SEM) images reveal that nickel addition changes the
      distributing configuration of Pd microparticles on GC. And the appearance of Pd
      Ni bimetal microparticles is distinctly different from that of single Pd and
      single Ni microparticles. Diameter of Pd-Ni microparticle is bigger than that of
      Pd microparticle and smaller than that of Ni microparticle. Effects of
      dechlorination current and time on removal efficiency of chloroform were also
      studied. The removal efficiency of chloroform increases at higher dechlorination
      current and longer dechlorination time. It reaches 42.53% when the dechlorination
      current and time are 0.5 mA and 180 min respectively on Pd-Ni/GC electrode
      prepared at optimum conditions. It can be envisioned that the removal efficiency
      of chloroform would increase further at longer dechlorination time.

PMID- 18624187
TI  - [Degradation of methyl tert-butyl ether (MTBE) by O3/H2O2].
AB  - The degradation of methyl tert-butyl ether (MTBE) in water solution has been
      studied using the combination of ozone/hydrogen peroxide in a bubble column.
      Effects of air (containing O3) currents, quantities of H2O2, initial
      concentrations of MTBE, pH values and temperatures on the oxidation of MTBE have
      been tested, and it is implicated that under the conditions of initial MTBE
      concentration of 10 mg x L(-1), air current of 0.5 L x min(-1), pH 6.5, 293 K and
      2.4 mg x L(-1) H2O2 addition, MTBE can be reduced by 75.5% and the removal rate
      of COD reaches 68.0% within 30 min. The main of degradation products identified
      are tert-butyl formate (TBF), tert-butyl alcohol (TBA), acetone (AC) and methyl
      acetate (MA). On the basis of that, the probable mechanism and pathway of the
      oxidation of MTBE by ozone/hydrogen peroxide have been proposed.

PMID- 18624189
TI  - [Degradation of malachite green in aqueous solution by Fe3+/H2O2 catalyzed with
      EDTA].
AB  - This study found that the discolorization of malachite green solutions (0.01
      mmol/L) was improved by Fe3+/H2O2 catalyzed with EDTA, at pH 7. Oxidation was
      carried out in presence of various hydrogen peroxide concentrations, in a wide
      range of temperature and EDTA concentration. It was found that oxidation with
      EDTA promoted the discolorization of MG from 43% to 98.3% as compared with the
      cases without EDTA. The discolorization of MG increased by 40% with the increase
      of EDTA concentration by 5 fold. The H2O2 concentration and temperature are
      higher, the discolorization of MG better, t-BuOH inhibited the improvement from
      EDTA. With the same total dosage of applied H2O2, the multiple steps addition did
      not show a much higher removal efficiency than that obtained by one step. OH free
      radical or an iron-oxo species may be the highly reactive oxidizing species, the
      latter may be the major oxidant. With the time, EDTA was a little oxidized.

PMID- 18624190
TI  - [Kinetics on ethanethiol oxidation by potassium permanganate in drinking water].
AB  - Reaction kinetics of ethanethiol oxidation with potassium permanganate in water
      was studied, and the effect of ethanethiol oxidation in raw water under
      coagulation condition has been investigated. The results showed that the
      oxidation reaction of ethanethiol by potassium permanganate was very efficient,
      the removing effect could be more than 90%. The rate of ethanethiol decomposition
      by potassium permanganate in aqueous solution followed second-order kinetics.
      When potassium permanganate was excessive, pseudo-first-order rate and
      concentration of potassium permanganate followed the equation: k' = 0.025 [KMnO4]
      - 0.008. And then, the second-order reaction rate constant was k = 0.025 L/(min x
      mg). The removal of ethanethiol in raw water by potassium permanganate under
      coagulation condition was poorer than in pure water condition, So predicted
      concentration of potassium permanganate was lower than real concentration.

PMID- 18624191
TI  - [Influencing factors on the paranitrobenzoic acid wastewater treatment by
      chlorine dioxide and activated carbon catalysis-oxidation technology].
AB  - The effect of activated carbon dosage, chlorine dioxide dosage, pH value and
      reaction time on the paranitrobenzoic acid wastewater treatment on chlorine
      dioxide (ClO2 ) and activated carbon (AC) catalysis-oxidation technology were
      analyzed, and the efficiencies of the process to remove COD and increase
      biodegradation capacity (BOD5/COD ratio) were also examined under the optimum
      conditions as the pretreatment method for paranitrobenzoic acid wastewater with
      high-concentration. The result showed that the COD removal efficiency of the
      ClO2/AC catalysis-oxidation system was 10% higher than that of the system with
      only ClO2 when the COD concentration of paranitrobenzoic acid wastewater was 10
      960 mg/L. It was also found that the COD removal was decreased by 35% with the
      concentration of 7 100 mg/L under the conditions of pH value 4.1, AC dosage 200
      g/L, reaction time 30 min and ClO2 dosage 300 mg/L. In addition, the BOD,
      concentration was increased to 1 810 mg/L and the biodegradability was improved
      greatly with the BOD5/COD ratio increased from 0.10 to 0.25. In a word, the
      chlorine dioxide (ClO2) and activated carbon (AC) catalysis-oxidation process is
      an effective pretreatment method for paranitrobenzoic acid wastewater treatment.

PMID- 18624192
TI  - [Mechanism and kinetic of methyldopa removal by Fenton's reagent].
AB  - Methyldopa was selected to be degraded by Fenton's reagent in the experiment. The
      experimental results showed that it was feasible to the removal of Methyldopa and
      COD by Fenton's reagent. The mechanism of Methyldopa removal by Fenton's reagent
      was significantly different according to the Fe2+ :H2O2 ratio. With high ratio of
      Fe2+ :H2O2 (> or = 2), the Fenton reaction was coagulation enhanced by H2O2. With
      medium ratio of Fe2+ :H2O2 (= 1), the Fenton reaction could be characterized into
      two specific systems : oxidation and coagulation. With low ratio of Fe2+ :H2O2 (<
      or = 0.2), the Fenton reaction was oxidation, including H2O2 oxidation catalyzed
      by Fe2+ and degradation by a hydrated ferryl-complex Fe(aq)4+. With the analysis
      of the mechanism according to low ratio of Fe2+ :H2O2 (< or = 0.2), a kinetics
      model was adopted to describe the reaction, and the rate equation could provide
      the evidence for the main reaction pathway, which was fitted very well with the
      experiment data for the relative error below 10%. It was showed that the kinetic
      models could primary describe the process of the removal of Methyldopa and COD by
      Fenton's reagent.

PMID- 18624193
TI  - [Kinetics and mechanism analysis of the degradation of hexachlorbenzene in water
      by advanced oxidation process].
AB  - The degradation characteristics and rule of hexachlorobenzen (HCB) in water were
      studied and the results were compared by the advanced oxidation process UV, O3
      and UV/O3. The experimental results showed that UV itself did not contribute to
      the removal of HCB obviously and HCB could be quickly degraded by O3 and UV/O3,
      namely UV < O3 < UV/O3. But in the case of O3 and UV/O3, raising the initial pH
      value of the system could not raise the removal rate of HCB, and the removal
      efficiency of 0.2 mg/L HCB could reach 50% within 40 min when the initial pH
      value was equaled to 3 and the degradation velocity could be accelerated in the
      acidic solution. Whether in the cases of ozone action alone or UV/O3 combined
      action, the degradation of HCB satisfied basically the rule of pseudo-first order
      reaction kinetics; and this rule was more remarkable if a constant pH value of
      the system was maintained. The degradation pathway and mechanism of HCB were
      discussed according to the measured results of the intermediated substances from
      the HCB degradation process by IC, GC and GC-MS.

PMID- 18624194
TI  - [Optimization of nitrogen and phosphorus removal in vertical subsurface flow
      constructed wetlands by using polypropylene pellet as part of substrate].
AB  - Constructed wetlands experiments were conducted by using shale and Typha
      latifolia L. as vertical subsurface flow constructed wetland substrate and plant
      for eutrophic Jin River water treatment, and part of shale with polypropylene
      pellet was replaced to investigate its effect on nitrogen and phosphorus removal.
      In this study, hydraulic loading rate was equal to 800 mm/d, theoretic residence
      time was equal to 12 h. During the entire running period, maximal monthly mean
      ammonia-nitrogen (NH(4+) -N), total nitrogen (TN), soluble reactive phosphorus
      (SRP) and total phosphorus (TP) removal rates were observed in August 2006. In
      contrast to the full shale used wetland, polypropylene pellet enhanced ammonia
      nitrogen, total nitrogen, soluble reactive phosphorus and total phosphorus
      removal by 13.38%, 8.9%, 9.29% and 8.25% respectively. After finishing the
      experiment, aboveground plant biomass (stems and leaves) of Typha latifolia L.
      was harvested, and its weight and nutrient content (total nitrogen and total
      phosphorus) were measured. Analysis of aboveground plant biomass indicated that
      polypropylene pellet restrained the increase in biomass but stimulated
      assimilation of nitrogen and phosphorus into stems and leaves. The subsequent
      harvesting of the plants resulted in the additional removal of total nitrogen and
      phosphorus of about 29.382 g x m(-2) and 13.469 g x m(-2), respectively.

PMID- 18624195
TI  - [Transformation of phosphorus forms in the sediments under the conditions of
      sediments re-suspension].
AB  - The change of phosphorus forms in sediments was studied and the possible path of
      transformation from mobile phosphorus into refractory forms was discussed under
      the conditions of sediments re-suspension, using sediments and overlying water
      from the trophic canal in the campus as material. The results showed that
      phosphorus release and adsorption had close relationships with the frequency of
      sediments resuspension. Various changes of different forms of sedimentary
      phosphorus were found under the conditions of sediments re-suspension. BD-P and
      NaOH-nrP were decreased obviously, while Ca-P was increased evidently. The change
      of other phosphorus forms was little. As a result, BD-P and NaOH-nrP could be
      transformed into Ca-P. Moreover, based on the formation of potentially mobile
      phosphorus (PMP) and bioavailable phosphorus (BAP), sediments re-suspension could
      improve the transformation from mobile phosphorus and bioavailable phosphorus
      into refractory forms and nonbioavailable forms, and the enhancement was improved
      with the increase of the frequency of sediments re-suspension.

PMID- 18624196
TI  - [Phosphate adsorption characteristics on surface sediments of Nansi Lake and its
      main inflow rivers].
AB  - Adsorption capacity, isotherms and kinetics of phosphate onto the 18 surface
      sediments taken from Nansi Lake and its main inflow rivers were investigated in
      laboratory, and the relationships between physical and chemical properties of the
      sediments and their phosphate adsorption characteristics are discussed. The
      results indicate that the phosphate adsorption characteristics of sediments that
      are at different trophic levels are similar. The amount of phosphate adsorbed
      within 10 h almost reaches or exceeds 80% of the maximum adsorption of phosphate
      and the maximum adsorption rates occur within 0-1.0 h. C(EPC) ranges from 0.010
      to 0.157 mg x L(-1), Q(max) from 86.74-118.32 mg x kg(-1), and TQ(max) from 99.97
      281.11 mg x kg(-1) in the study. Between Ads-P and its c(EPC), NAP, m, Q(max) and
      TQ(max) have remarkable positive correlation. The content of Ads-P will serve as
      a index indicating the polluted level in Nansi Lake. Adsorption efficiency (m)
      has remarkable positive relationship with TQ(max). The m is the sum of adsorption
      efficiency of the sediments adsorbing the phosphorus coming from external and the
      phosphorus desorbed from the sediments. The NAP has positive correlation with
      c(EPC) and the trend is that the sediment with higher NAP easily desorbs
      phosphorus to the water, contrarily the sediment with lower NAP easily adsorbs
      phosphorus.

PMID- 18624197
TI  - [Relation between distribution of phosphorus form in the sediment of typical
      urban shallow lakes and eutrophication].
AB  - The forms of phosphorus in the surface sediments were extracted and determined
      sequentially with ethylene dinitrilo tetracetic acid (EDTA) technique in three
      urban shallow lakes: Lake Xuanwu, Lake Mochou and Lake Daming. The results showed
      that the iron and calcium-bound phosphate, about accounting for 80%, were the
      main forms of total phosphorus. The contents of iron bound phosphate in Lake
      Xuanwu and Lake Mochou were higher than that of Lake Daming, reaching 30%-40%.
      The organic phosphorus existed mainly in the form of alkali extractable
      phosphorus, while the contents of acid extractable organic phosphorus were low.
      However, the proportion of acid extractable organic phosphorus to the total
      phosphorus can indicate the degree of lake eutrophication.

PMID- 18624198
TI  - [Elasticity plastic filler for purification of polluted streams in situ entering
      lake].
AB  - The biofilm process using a new-type elasticity plastic filler was adopted in a
      typical polluted stream entering the Tai Lake (the Linzhuanggang). The
      experiments at pilot scale ran for about 0.5 years. Results show the average
      removal percentage of permanganate index by biofilm attached to the elasticity
      plastic filler is about 5.4%, the biggest removal percentage is 9.9%, the average
      removal percentage of NH(4+) -N is approximately 5.35%-39.91%, the biggest
      removal percentage of TP is 28.6%. And the bacteriological experimental results
      show there is the same change laws between the removal percentage of permanganate
      index and the numbers of heterotrophic bacteria; the numbers of ammonia-oxidizing
      bacteria (AOB) and nitrite-oxidizing bacteria (NOB) are matching with removal of
      NH(4+) -N.

PMID- 18624199
TI  - [Comparison of overwintering and rrecruitment of cyanobacteria in Taihu Lake and
      Chaohn Lake].
AB  - Dynamics of overwintering and recruitment of cyanobacteria were studied in Taihu
      Lake and Chaohu Lake. The results demonstrated that cyanobacteria sank to the
      sediment in autumn (November) and recruited to water column in May in Taihu Lake.
      From November to next May, the cyanobacteria kept growing with an increased
      growth rate from March to May in the sediment. A similar pattern of overwintering
      and recruitment of cyanobacteria was found in Chaohu Lake, which showed the
      cyanobacteria sinking in November and recruitment in spring with the
      cyanobacteria growing in the sediment, while the cyanobacteria recruited to water
      column from March to April. Our results showed there was typical overwintering
      and recruitment of cyanobacteria in Taihu Lake and Chaohu Lake. The numbers of
      cyanobacteria in sediment represented by the almost same pigments content in
      different lake areas of Taihu Lake according to nutrient levels probably implied
      the little relationships of the numbers in sediments with the summer bloomed
      biomass of cyanobacteria.

PMID- 18624201
TI  - [Uniform model and experimental method of anaerobic inhibition dynamics using
      table function].
AB  - To figure out the problem, such as disunity of existent form in the model of
      traditional inhibition dynamic, and difficulty to obtain the parameters, we adopt
      the way of table function to formulate inhibition kinetics. Through indraught the
      way of table function to improve on the way of experiment in dynamic mensuration,
      DYNAMO software was used to process the data and simulate the inhibition
      phenomena of 2,4 dinitrophenol. The result shows that the table function is
      possible to simulate the inhibition phenomena. Compared with the traditional
      inhibition dynamic, the simulation curve of table function is much more close to
      the data of experiment, the modality is simple and unify, and simultaneously it
      solves the problem of parameter obtaining. When the complex inhibition phenomena
      is simulated, the table function shows obvious advantage, and may predigest the
      structure of model at a certain extent.

PMID- 18624200
TI  - [Influence of landscape characteristics on non-point source pollutant output in
      Taihu upper-river basin].
AB  - Based on the observed data in monitored drainage areas and GIS spatial analysis
      tools, watershed basic database of Taihu upper-river basin was built. Using the
      methods of multiple stepwise regression and redundancy analysis, the influence of
      landscape characteristics on non-point source pollutant output at the outlets of
      watersheds and their relative influence intensity were analyzed. The dominant
      landscape characteristics influencing non-point source pollutant output in Taihu
      upper-river basin and sub-watersheds were also illustrated. The results show that
      there are strong correlations between non-point source pollution and landscape
      characteristics, in which land use makes the most remarkable effect, followed by
      soil characteristics and average slope and watershed area in turn. Residential
      land proportion, farmland proportion and average terrain slope with higher
      importance and significance level, are the dominant landscape characteristics
      variables affecting non-point source pollutant output of watersheds. 59.5% of
      water quality information and 98.6% of relation information between landscape
      characteristics and water quality can be explained by these three variables.
      Furthermore, the contribution rates of these three landscape characteristics to
      non-point source pollutant output in each sub-watershed are different.

PMID- 18624202
TI  - [QSPR study on the lipid-water partition coefficients of dioxins based on DFT].
AB  - With computational method of density functional theory (DFT), quantified model
      study of equilibrium partitioning properties of polychlorinated dibenzo-p-dioxins
      (PCDDs) and dibenzofurans (PCDFs) between lipid phase of organism (Poecilia
      reticulata) and water phase was carried out based on quantum chemical and further
      calculated parameters, namely frontier orbital energies, entropies, traceless
      quadrupole moments as well as molecular absolute hardness, electronegativities
      and electrophilicity indices, which all were derived from full geometry
      optimization of PCDD/Fs. Through multiple linear regression (MLR) analyses,
      quantitative structure-property relationship (QSPR) was successfully proposed in
      the form of multi-parameter quadratic function: lgK(hw) = 5.343 - 0.001(S -
      125.480)(2) - 0.355(omega - 3.239)(2) + 0.006( Q = - 2.950)(2) - 22.728(eta -
      2.365)(2). It was shown that the obtained QSPR had higher goodness of fitting and
      robustness, determination coefficient and cross-validated correlation coefficient
      being 0.943 and 0.908 respectively, and it was also provided with ideal interior
      and exterior predictive abilities so that it could be used for prediction of
      unknown lipid-water partitioning properties. By comparison, QSPR in this research
      was superior to that from previous SOFA (solubility parameter for fate analysis)
      method on the whole. Lipid-water partitioning properties (coefficients) of
      PCDD/Fs should be mainly related to molecular volume and aryl hydrocarbon
      molecular interactions determined by charge distribution. To a certain degree,
      they also might be influenced by potential biotransformation and molecular
      reactivity.

PMID- 18624203
TI  - [Distribution of typical organic pollutants in benthic mussels from the inshore
      areas of Yellow Sea].
AB  - Based on the second national baseline survey on marine pollution, the
      concentration, distribution and potential ecological risk of typical organic
      pollutants in the benthic mussels from the inshore areas of Yellow Sea were
      determined. The results indicated that, at over 35% of the total sampling sites,
      the tissue concentrations of petroleum hydrocarbons were higher than the Category
      I (15 000 ng/g) of the national marine biological quality standards, and at the
      sites near Dalian Bay, the tissue concentrations even exceeded the Category II
      (50 000 ng/g). At minor sites located in Dalian Bay, Weihai and Jiaozhou Bay,
      relatively high concentrations of polycyclic aromatic hydrocarbons (PAHs) and
      phthalate esters (PAEs) occurred, while the concentrations of PAHs and PAEs in
      mussels at most other sites were low. The dominant median and high rings
      components indicated pyrolytic procedures as the main source of local PAHs, and
      DBP and DEHP were the major constitution of phthalate esters. At all the sites,
      the tissue concentrations of PCBs were generally low (< 10 ng/g). The sites with
      DDTs concentrations over the Category I of the national quality standards were
      mainly situated in the southern coasts of Yellow Sea, and the predominant
      fractions were the metabolites of DDT, i.e., DDD and DDE. p, p'-DDT was detected
      in mussel species at all the monitoring sites, especially at the sites close to
      Dalian Bay and Penglai (fraction > 50%), which indicated potential inputs from
      the neighboring areas. Accordingly, petroleum hydrocarbons and PAHs in mussels at
      the coastal areas of Dalian Bay, Weihai and Jiaozhou Bay were high, the tissue
      DDTs levels at the sitesnear Jiaozhou Bay and Haizhou Bay were high, these sea
      areas had therefore higher ecological risk, and new inputs of DDT in the inshore
      areas of Dalian Bay and Penglai may threat on the benthic surroundings.

PMID- 18624204
TI  - [Growth of Tubificidae in activated sludge].
AB  - The growth of Tubificidae was investigated from juvenile to adult stage for 16
      weeks by cultivating Tubificidae with activated sludge as substrate in batch
      tests at two different temperatures (20 degrees C and 25 degrees C), monitoring
      changes of body length and wet weight of Tubificidae. Results showed that the
      growth of Tubificidae well fit the Logistic curve. Temperature of 25 degrees C
      was more suitable for worm growth than of 20 degrees C with the growth rates of
      wet weight and body length of 0.0470 mg x (ind x d)(-1) and 0.1936 mm x (ind x
      d)(-1), respectively, at 25 degrees C. Meanwhile, the relationship between body
      length and wet weight of Tubificidae at 25 degrees C was determined as W = 0.008
      L(2.028) (R2 = 0.868 5), which was well in accordance with the common regulation
      concluded in previous studies. Compared with other substrates, Tubificidae showed
      little difference on growth when fed with activated sludge.

PMID- 18624205
TI  - [Effects of nitrogen on performance and yeast morphology of yeast-SBR system].
AB  - Effects of nitrogen on yeast cell morphology, settleability and performance of
      wastewater treatment were investigated in treating oil-containing wastewater by
      yeast-SBR system. The results show that: nitrogen supply affects directly yeast
      biomass, settleability, pH and treatment efficiency of system; the absence of
      nitrogen induces the transformation of certain yeast cells from single cell to
      hypha morphology. Based on an overall consideration of efficiency and stability
      of yeast-SBR system, the optimum BOD/N ratio of influent is 20/1. The optimum
      nitrogen supply can improve wastewater treatment efficiency of systems with
      different degrees of nitrogen absence and make yeast morphology become the
      predominant morphology for slightly mycelial system over a short time, but for
      severe mycelial system, the hypha morphology still keeps dominant.

PMID- 18624206
TI  - [Evaluation of the damaging effect of dyestuff on Phanerochaete chrysosporium
      with amplified fragment length polymorphism (AFLP) analysis].
AB  - The AFLP analysis was carried out in order to evaluate the DNA damaging effects
      of dyestuff of different concentrations on Phanerochaete chrysosporium. The DNA
      similarity and UPGMA cluster analysis were conducted to determine the
      relationships between the concentrations of dyestuff and DNA damaging effects.
      The results showed that the AFLP analysis could reflect the polymorphisms of DNA
      well, and the primer pairs E-AAC/M-CAA could give more amplified DNA fragments
      than others primers. From the DNA maps of best primer pairs, 35 clear and stable
      DNA bands were observed, including 12 polymorphous bands which were accounted for
      34.3% diversity. It was indicated from the DNA similarity and UPGMA cluster
      analysis that DNA polymorphisms correlated with dyestuffs concentrations well. If
      the concentration of dyestuff was not higher than 50 mg/L, the damaging effect on
      DNA was finite. If the concentrations of dyestuff were up to 300 mg/L, the DNA of
      Phanerochaete chrysosporium would have been injured greatly, and would have been
      bankrupted in its intrinsic function.

PMID- 18624207
TI  - [Isolation and identification of imazethapyr degradable bacteria and its
      degradation characteristics].
AB  - One strain of imazethapyr degradable bacteria was isolated from the mixture of
      imazethapyr production factory's sludge and the soil that was contaminated with
      imazethapyr for a long time. The strain could degrade imazethapyr more than 90%
      within 72 h when it grew in 500 mg/L imazethapyr condition. When pH was 5, the
      bacteria could degrade all the imazethapyr of 500 mg/L in 72 h, but when pH was 8
      and 9, only 50% imazethapyr was degraded which showed acid condition was more
      compatible than that of alkalescency for this bacteria growing. The higher
      degradation ratio at 25 degrees C and 30 degrees C was observed and the optimum
      condition for the bacteria to degrade imazethapyr was pH = 5 and 25 degrees C.
      Characterizing by physiological and biochemical properties as well as 16S rRNA
      sequence analysis, the strain is related and shared characteristics of the genus
      Alcaligenes sp.

PMID- 18624208
TI  - [Sorption characteristics of veterinary antibiotics chlortetracycline on manure].
AB  - The sorption characteristics of high-use tetracycline veterinary antibiotics
      chlortetracycline (CTC) on pig manure and chicken manure were investigated in
      laboratory according to the OECD guideline 106. The results showed that CTC was
      strongly and rapidly adsorbed to the two manures and Freundlich model could
      describe preferably the CTC nonlinear sorption isotherms. The adsorbed CTC was
      difficult to be desorbed by rain with desorption H of 1.522 for pig manure and
      1.329 for chicken manure, respectively. Only 18.3%-20.4%, 18.7%-19.4% and 55.7%
      57.6% adsorbed CTC were desorbed by methanol, 3 mol/L NaCl and 3 mol/L MgCl2. The
      sorption of CTC on manure were affected by solution pH and ionic strength, the
      amount of adsorbed CTC on manure decreased with an increase of pH value and ionic
      strength, and greater sorption effect in the Ca systems than the Na systems was
      observed. These results suggest that organic matter and cation exchange mainly
      contribute to the sorption of CTC on manure.

PMID- 18624209
TI  - [Diuron degradation process and change of toxicity by gamma-irradiation].
AB  - The radiation-induced degradation process of diuron and change of toxicity by
      gamma-irradiation were investigated. The contribution to diuron degradation by
      the radicals is in the order of: *OH > e(aq)(-) > *H. The quantum efficiency
      ratios of *OH, e(aq)(-) and *H for the degradation of diuron are calculated as 3
      : 1 : 2. e(aq)(-) and *H could reduce diuron and its degradation product by loss
      of the chlorine atoms and the addition reaction. Both the shift and alkaline
      substitute mutations firstly increase and then decrease with the increase of
      irradiation time. But, the sample only shows mutagenic potential in Ames assay
      (TA100 strain) when 22.2 min is selected as the irradiation time. The acute
      toxicity firstly decreases and then increases with the increase of irradiation
      time and the more toxic substances are produced.

PMID- 18624210
TI  - [Characteristics of six elements contents in human hairs in the vicinity of metal
      smelting factories].
AB  - To assess the impact of secondary smelting activities to the local resident's
      well beings, the contents of six elements-Cu, Zn, Pb, Cd, As, Se-in human scalp
      hairs of residents in suburb Fuyang, Zhejiang Province, were determined by atomic
      absorption spectrometer (AAS) and by atomic fluorescence spectrometer (AFS-930),
      respectively. The results showed that hair elemental contents were markedly
      higher than those in unpolluted area. The highest hair contents of Cu, Zn, Pb and
      Cd reached 312, 513, 700 and 7.41 microg x g(-1), respectively, As and Se 10.08
      and 0.85 microg x g(-1), respectively. Additionally, a significant relationship
      between Cu, Zn, Pb, Cd and As in human hair was observed, which indicated at a
      certain degree that the elemental pollution was caused by similar source-small
      blast furnace smelting. Moreover, it showed that the Cu, Zn, Pb, Cd, and As
      contents in hair of human who were above 40 years old was twice more than those
      whose age below 40. There was no apparent difference in average content of Cu,
      Zn, Cd, Se between male and female, except that Pb and As of male hair was higher
      than female, however, by statistic analysis showing no significant age and gender
      dependence.

PMID- 18624211
TI  - [Influence of freshwater marsh tillage on microbial biomass and dissolved organic
      carbon and nitrogen].
AB  - The changes in microbial biomass carbon (MBC), microbial biomass nitrogen (MBN),
      dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) were examined
      in order to assess the effect of surface layer soil (0 - 10 cm) under different
      land-use types after freshwater marshes tillage in the Sanjiang Plain Northeast
      China. Land uses were Deyeuxia angustifolia freshwater marshes ((DAM), cultivated
      land (CL), recovery freshwater marsh (RFM), constructed woodland (CW). After DAM
      soil tillage, MBC, MBN, DOC and DON declined strongly in agricultural surface
      soil layer, decreased 63.8%-80.5% (MBC), 56.3%-67.1% (MBN), 43.1%-44.3% (DOC) and
      25.2%-56.1% (DON) respectively. In contrast, these C, N fraction had significant
      recovered in RFM and CW surface soil, increased 36.1%-59.9% (MBC), 46.7%-65.9%
      (MBN), 67.0%-69.3% (DOC)and 81.2%-88.3% (DON) respectively. Cultivation and land
      use affected soil MBC, MBN, DOC and DON intensely. Therefore these labile C, N
      fractions have the significant relative under different land-use types. However
      DOC was more obvious controlled than DON by the land-use types. The relative
      between DOC and MBC, MBN have much difference than DON, the main reason of this
      distinction is the diverse source in available carbon and nitrogen that taken by
      microbial property under different land uses.

PMID- 18624212
TI  - [Variation of below-ground carbon sequestration under long term cultivation and
      grazing in the typical steppe of Nei Monggol in North China].
AB  - Human activities have changed the earth surface mostly, which caused many
      environment issues now. We aimed to detect the process that human activities
      exert on ecosystem by investigating and analyzing the changes of plant community,
      especially underground soil and root carbon sequestration under long-term
      cultivation and grazing in typical steppe area of Nei Monggol, North China. The
      carbon sequestration on the root and soil in three plots of typical steppe area:
      26-year exclosure grassland (E26), continuous grazing grassland (LG) and 35-year
      cultivated tillage (LC) were measured. The carbon storage in the layer of 0-40 cm
      showed a trend that E26 (7 307.59 g x m(-2) and 950.32 g x m(-2)) approximately
      LG (7834.01 g x m(-2) and 843.43 g x m(-2)) > LC (4537.04 g x m(-2) and 277.35 g
      x m(-2)), occupied 88.49%, 90.28% and 94.24% of total soil-root carbon
      respectively. The original composition structure of plant-soil system was
      completely destroyed by human cultivation, and it also led to sever soil erosion
      as well. The sand content in soil of LC at layers 0-10 cm, 10-20 cm were
      increasing by 81% and 39% compared to E26. On the other hand, the root biomass of
      LG at 0-40 cm decreased by 71%. Cultivation resulted in significant decrease of
      the carbon storages in soil and root. Therefore, the present cultivation should
      be ceased and the optimum measurements should be taken to make the tillage
      restore to natural grassland condition. Continuous grazing led to the
      significantly changes of the above-ground vegetation characteristics such as
      community height, coverage and biomass. While the changes of soil organic content
      and root biomass was not remarkable under grazing. However, the bulk density of
      surface soil (0-10 cm) exhibited significant increase in LG compared to E26,
      which indicated that the present grazing pressure have been reaching the
      threshold of grassland capacity. Therefore, the present grazing pressure should
      be decreased properly in order to avoid more serious degradation.

PMID- 18624213
TI  - [Influences of land using patterns on the anti-wind erosion of meadow grassland].
AB  - In order to analyse the effects of the human disturbances to the ability of anti
      wind erosion of the Hulunbuir meadow grassland, the methods of vegetation
      investigation and the wind tunnel experiment were made to research the changes of
      vegetation and the abilities of anti-wind erosion of meadow grassland under
      different using patterns of meadow grassland. The results indicate that, under
      different grazing intensities of meadow grassland, the critical wind velocity of
      soil erosion (v) changes with the vegetation cover according to the relation of
      second power function. Along with the grazing intensities increasing and the
      vegetation cover reducing, the velocity of soil erosion rapidly increased on the
      condition of similar wind velocity which is speedier than the critical wind
      velocity of soil erosion. When the meadow grassland is mildly grazed which the
      vegetation cover maintains 63%, the velocity of soil erosion is small even there
      is gale that the wind velocity reach 25 m/s. When the vegetation cover of meadow
      grassland reduced to less than 35%, the velocity of soil erosion rapidly
      increased with the vegetation cover's reducing on the condition of the wind
      velocity is among 20-25 m/s. And owing to the no-tillage cropland of meadow
      grassland is completely far from the protection of the vegetation, the soil wind
      erosion quantity achieves 682.1 kg/hm2 in a minute when the wind velocity is 25
      m/s, which approaches the average formation quantity of soil (1 000 kg/hm2) in a
      year.

PMID- 18624214
TI  - [Relationships between soil and environment in peak-cluster depression areas of
      Karst region based on canonical correspondence analysis].
AB  - Karst region is a typical ecological fragile zone, with small environmental and
      anti-interference capability. Many environment factors, such as different land
      use, elevation and topographic relief, have significant influence on spatial
      variability of soil properties, resulting in abnormal fragments of landscape and
      severe rocky desertification. The method of canonical correspondence analysis
      (CCA) was employed to reveal the relationships between soil and environment in
      peak-cluster depression areas of karst region, using the samples from field
      survey in Guzhou. Results show that spatial variability of TN, AN, SOC, AP, AK
      and C/N are greater than TP, TK, and pH, with the similar trend among TN, AN and
      SOC. Furthermore, CCA shows that SOC, TN and AN have high correlation with bare
      rock rate and grade, AK and vegetation type, together with the significant
      correlation between C/N and soil depth, while the environment has little effect
      on TK, TP and pH. Environmental factors that affect soil properties are listed as
      the following order: land use > vegetation type > bare rock rate > aspect > soil
      depth > elevation. Except TK and pH, soil properties are significantly affected
      by different land-use types.

PMID- 18624215
TI  - [Kinetics and thermodynamics of Cd (II) adsorption onto particle-sized fractions
      of yellow-brown soil].
AB  - A batch method was used to investigate the kinetics and thermodynamics of cadmium
      adsorption onto different particle-sized fractions (2 000 - 200 microm, 200 - 20
      microm, 20 - 2 microm and 2 - 0 microm, which were named coarse sand, fine sand,
      silt and clay respectively according to international system) derived from yellow
      brown soil by using a novel technology combined with wet sieving, sedimentation
      siphoning and centrifugation method. The results showed that the reaction of
      adsorption can be divided into two types: a fast reaction in the first 15 min and
      a slow reaction in the later reaction course. The amounts of Cd2+ adsorbed by the
      fast reaction exceed 95% of the adsorption capacity. As the temperature increased
      from 25 degrees C to 45 degrees C, the adsorption capacities of the four
      fractions increase by 4.86%-25.3%. First-order rate equation and pseudo second
      order rate equations were applied to express adsorption kinetics. Adsorption
      processes for Cd2+ onto the four fractions were found to follow pseudo-second
      order type adsorption kinetics. The pseudo second-order rate constants exhibited
      that adsorption speed to reach equilibrium decreased with the increase of
      particle size. Intra-particle diffusion might be the major rate-limiting step.
      Thermodynamic parameters including deltaH0, deltaS0 and deltaG0 were also
      calculated from graphical interpretation of the experimental data. Positive
      deltaH0 values indicated the adsorption processes to be endothermic. Negative
      deltaG0 values implied that adsorption reaction was a spontaneous process.

PMID- 18624216
TI  - [Ionic exchange modification mechanism between organic modifier and Lou soil].
AB  - The ionic exchange modification mechanism between cationic organic modifier,
      cetyltrimethylammonium bromide (CTMAB), and two layers of Lou soil, tillage layer
      (TLLS) and clay layer (CLLS), were studied. The results show that a simple and
      effective index, sum of amounts of CTMAB and Ca2+/2 (Scc), can be used to judge
      the essence of modification mechanism between CTMAB and Lou soil. St(CC)
      demonstrates that the modification of CTMAB to two layers of Lou soil is the
      coexist of both ionic exchange and hydrophobic bond mechanism. The hydrophobic
      bond modification appears in the range of modification ratio 20%-28% CEC and
      linearly increases with an increase of both modification ratio and molar fraction
      of CTMAB, but its effects on the properties of soil become emergence just until
      50% CEC modification ratio, and the hydrophobic bond mode exceeds the ionic
      exchange mode at about 100% CEC modification ratio and becomes main modification
      mechanism. The Vanselow selectivity coefficients show that the adsorption
      preference of Lou soil to CTMAB is stronger than that to calcium ion. The results
      of thermodynamics indicate that with an increase of modification ratio, the
      modification reaction transform from exothermic and entropy decrease to
      endothermic and entropy increase in the range of modification ratio 25% -100%
      CEC, while both pseudo enthalpy change and pseudo entropy change display a
      decrease trend in the range of modification ratio 100%-200% CEC, and in total,
      the modification reaction is a spontaneous reaction which controlled by entropy
      change in range of modification ratio 25% -100% CEC but controlled by enthalpy
      change in range of modification ratio 100%-200% CEC. The rationality of
      modification mechanism could be demonstrated by the results of thermodynamics.

PMID- 18624217
TI  - [Effect of low-molecular-weight organic carbon on anaerobic degradation and
      volatilization of hexachlorobenzene in soils].
AB  - Batch incubation experiments in aid of anaerobic incubation flask were conducted
      to study the anaerobic degradation and volatilization of hexachlorobenzene (HCB),
      the change of pH in soil, the emission of CH4 and CO2, and the volatilization of
      HCB in the Hydragric Acrisol and Gleyi-Stagnic Anthrosol added with acetic acid,
      glucose and citric acid. Results showed that HCB was reduced by 20%-44% in
      Hydragric Acrisol during 8 weeks, and addition of acetic acid inhibited the
      dechlorination, indicating that dechlorination was impeded at low pH. Addition of
      glucose or citric acid decreased the dechlorination rate initially and then
      increased it. HCB was reduced by 21%-23% in Gleyi-Stagnic Anthrosol, and there
      was no obvious effect by adding low-molecular-weight organic carbon. The main
      product of HCB anaerobic dechlorination was pentachlorobenzene (PCB), which were
      23-96 microg/kg and 64-92 microg/kg in Hydragric Acrisol and Gleyi-Stagnic
      Anthrosol respectively. Furthermore, the degradation of HCB had no statistically
      significant correlation with the productions of CH4 and CO2. Addition of low
      molecular-weight organic carbon reduced HCB volatilization, which was stronger in
      Hydragric Acrisol than in Gleyi-Stagnic Anthrosol, indicating that soil organic
      matter was an important factor in HCB volatilization.

PMID- 18624218
TI  - [Humus composition of petroleum hydrocarbon-contaminated soil].
AB  - An abandoned petroleum well which had been exploited for about twenty years in
      Songyuan city of Jilin Province, China, was selected to study the compositions
      and characteristics of soil humus using revised humus composition method and
      Simon-Kumada method. Soil samples were collected at 0.5, 1.5, 2.5, 3.5, 4.5, 5.5,
      6.5, 7.5 and 10.5 m apart from the well head. Results show that the petroleum
      contents increase from 0.08 g/kg (10.5 m to the well head) to 153.3 g/kg (0.5 m
      to the well head). With the increase in petroleum content, the contents of soil
      organic carbon and water soluble organic carbon increase; for total soil humus,
      the contents of extractable humus (HE) and humic acid (HA) decrease whereas that
      of humin (HM) increase; the percentage of HA/HE (PQ 72.0%-8.05%) decrease and
      HM/HE ratio (31.4-76.7) increase; for different combined humus, the contents of
      loosely combined humus (HI) and stably combined humus (HII) have a decrease
      tendency while that of tightly combined humus (HIII) increase; the HI/HII ratio
      (0.19-0.39) shows an increase tendency, whereas HI/HIII ratio (0.032-0.003) and
      HII/HIII ratio (0.096-0.009) decrease; the PQs of HI (3.21%-1.42%) and HIII
      (58.1%-35.5%) also decrease, and the range of PQ change is less in HI than in
      HII; the color coefficient (deltalogk) of water soluble organic matter (WSOM)
      decreases, whereas no obvious change for HA. The above results indicate that
      petroleum hydrocarbon promotes the formation of HM but not HA. The decrease in HA
      is mainly due to the restraining effect of petroleum hydrocarbon on the formation
      of stably combined HA. Petroleum hydrocarbon leads molecular structure of WSOM
      more complex but no effect on molecular structure of HA.

PMID- 18624219
TI  - [Transport characteristics of air pollutants over the Yangtze Delta].
AB  - Meteorological field of January, April, July and October in 2004 was obtained by
      running MM5 with NCEP datasets. Then we used HYSPLIT 4.8 model to calculate the
      backward and forward trajectories of representative cities. Distributions of
      trajectories and the affected areas vary with seasons. Transport current
      affecting Yangtze River Delta is mainly from Mongolia, North China or Northeast
      region, via Yellow Sea area, Shandong, Jiangsu province or Shanghai. Another
      important transport path is current from southwest because of the Southwest
      monsoon. A movement of East Asia monsoon plays an important part in the mesoscale
      transport of pollutants in Yangtze Delta. Winter monsoon is a main mechanism
      which moves the air pollutants in Yangtze Delta to South China and West Pacific
      ocean. Another important transport system is the subtropical anticyclone over the
      western Pacific Ocean which controls the east coast of our country in spring and
      summer. This circulation system mainly affects the inland area of our country.

PMID- 18624220
TI  - [Volatile organic compounds concentrations and sources inside new air-conditioned
      bus].
AB  - The distributing profile and concentration level inside new air-conditioned buses
      with 53 seats have been determined using the method of thermal desorption
      capillary GC/MS under vehicle static conditions. Compounds were identified from
      their mass spectral data by using US National Institute of Standards and
      Technology (NIST02). The total numbers of identified components were 33 inside
      buses, including alkenes (15,45.4%), aromatic compounds (9,27.3%), alcohols
      (4,12.1%), ketones (3,9.1%) and esters (2,6.1%), especially in the range of C6
      C10. The top 5 compounds measured inside buses were decane (8.01 mg/m3), 3
      methylhexane (7.10 mg/m3), heptane (5.10 mg/m3), isoheptane (4.20 mg/m3) and 1
      Methyl-3-ethylbenzene (3.56 mg/m3), and total volatile organic compounds (TVOC) >
      52.5 mg/m3. The main sources of in-vehicle hydrocarbons and aromatic compounds
      comes from cabin components and interior trim materials (e.g., sealants, carpets,
      adhesives, paints, leather, plastics, PU foam and PE foam) that may retain
      certain VOCs during manufacturing, and/or emit these compounds over an extended
      period of time from off-gassing, aging-related breakdown products,
      heating/cooling and so on.

PMID- 18624221
TI  - [Removal of odors from fermentation process of MSW biological mechanical
      treatment using compost biofilter].
AB  - For the odour from fermentation processing of municipal solid waste biological
      mechanical treatment, a compost biofilter was established to investigate its
      performance and the characteristics change of compost. The component and TVOC
      concentration in odors, removal efficiency of biofilter, and total carbon (TC),
      total nitrogen (TN), total phosphorus (TP), organic matter (OM), pH value and
      bacterial colony in compost media were measured respectively. SPME-GC-MS analysis
      showed that the main components of odors were BTEX, terpenes and alkane. The
      range of TVOC concentrations in odors during a fermentation process period and
      removal efficiencies of biofilter were 68.3 x 10(-6) -3.3 x 10(-6) (volume
      fraction), 31.5%-84.8% respectively. After about 4 months operation, TN, TC, TP
      and OM in compost were kept almost stably, but the dissolved N experienced an
      increase of 53.7%, and the dissolved P decreased 19.6%. The pH value experienced
      an increase in the former period and kept stable finally at about 7.8, which
      excursion was from 7.49 to 7.86. Analytical results for bacterial colony in
      packing material indicated that bacteria and mould colony counts increased, but
      yeasts and actinomyces decreased along with biofilter operation, which were 3.1,
      3.4, 0.04, 0.07 times of their initial values respectively.

PMID- 18624222
TI  - [Effects of chlorides on Cd partitioning and speciation in a simulated MSW
      incinerator].
AB  - The effects of chlorides (including inorganic chloride NaCl and organic chloride
      PVC) on Cd emission in MSW (municipal solid waste) incineration was investigated
      using a simulated tubular furnace and the simulated MSW spiked with heavy metals.
      The concentrations of heavy metals were measured by ICP-AES after the digesting
      of samples including bottom ash, fly ash and flue gas according to related USEPA
      Methods. Heavy metal species in bottom ash and fly ash were identified by X-ray
      diffraction technique and the spectra of elements distributed and micrographs of
      bottom ash and fly ash were detected by energy dispersive X-ray system and
      scanning electron microscope, respectively. The results indicated that the
      emission of Cd tended to be enhanced with the increasing of chloride content, and
      97% Cd partitioned in fly ash after spiked chlorides. However, the content effect
      of inorganic chloride NaCl and inorganic chloride PVC on Cd emission had no
      significant difference. The effect of PVC on Cd partitioning was affected by
      temperature, 80.51% Cd partitioned in fly ash at 550 degrees C and 97.91% Cd
      partitioned in fly ash at 850 degrees C, when temperature went above the melting
      point of CdCl2 (568 degrees C), the effect of temperature became less important.
      The effect of NaCl on Cd partitioning was not affected by temperature, 95.02% Cd
      partitioned in fly ash at 550 degrees C and 96.58% Cd partitioned at 1 000
      degrees C when spiked NaCl. Residence time had no significant effect on Cd
      partitioning with spiked chlorides. The two different mechanisms of chlorides
      effects on Cd emission were identified by bottom ash and fly ash analysis using
      SEM/EDS and XRD technique.

PMID- 18624223
TI  - [Optimization of fuel ethanol production from kitchen waste by Plackett-Burman
      design].
AB  - Kitchen garbage was chosen to produce ethanol through simultaneous
      saccharification and fermentation (SSF) by Zymomonas mobilis. Plackett-Burman
      design was employed to screen affecting parameters during SSF process. The
      parameters were divided into two parts, enzymes and nutritions. None of the
      nutritions added showed significant effect during the experiment, which
      demonstrated that the kitchen garbage could meet the requirement of the
      microorganism without extra supplementation. Protease and glucoamylase were
      determined to be affecting factors for ethanol production. Single factor
      experiment showed that the optimum usage of these two enzymes were both 100 U/g
      and the corresponding maximum ethanol was determined to be 53 g/L. The ethanol
      yield could be as high as 44%. The utilization of kitchen garbage to produce
      ethanol could reduce threaten of waste as well as improve the protein content of
      the spent. This method could save the ethanol production cost and benefit for the
      recycle of kitchen garbage.

PMID- 18624224
TI  - Clinical and molecular diagnosis of a Costa Rican family with autosomal recessive
      myotonia congenita (Becker disease) carrying a new mutation in the CLCN1 gene.
AB  - Myotonia congenita is a muscular disease characterized by myotonia, hypertrophy,
      and stiffness. It is inherited as either autosomal dominant or recessive known as
      Thomsen and Becker diseases, respectively. Here we confirm the clinical diagnosis
      of a family diagnosed with a myotonic condition many years ago and report a new
      mutation in the CLCN1 gene. The clinical diagnosis was established using ocular,
      cardiac, neurological and electrophysiological tests and the molecular diagnosis
      was done by PCR, SSCP and sequencing of the CLCN1 gene. The proband and the other
      affected individuals exhibited proximal and distal muscle weakness but no
      hypertrophy or muscular pain was found. The myotatic reflexes were lessened and
      sensibility was normal. Electrical and clinical myotonia was found only in the
      sufferers. Slit lamp and electrocardiogram tests were normal. Two affected
      probands presented diminution of the sensitive conduction velocities and
      prolonged sensory distal latencies. The clinical spectrum for this family is in
      agreement with a clinical diagnosis of Becker myotonia. This was confirmed by
      molecular diagnosis where a new disease-causing mutation (Q412P) was found in the
      family and absent in 200 unaffected chromosomes. No latent myotonia was found in
      this family; therefore the ability to cause this subclinical sign might be
      intrinsic to each mutation. Implications of the structure-function-genotype
      relationship for this and other mutations are discussed. Adequate clinical
      diagnosis of a neuromuscular disorder would allow focusing the molecular studies
      toward the confirmation of the initial diagnosis, leading to a proper clinical
      management, genetic counseling and improving in the quality of life of the
      patients and relatives.

PMID- 18624225
TI  - Fine scale gene flow and individual movements among subpopulations of Centrolene
      prosoblepon (Anura: Centrolenidae).
AB  - Dispersal capabilities determine and maintain local gene flow, and this has
      implications for population persistence and/or recolonization following
      environmental perturbations (natural or anthropogenic), disease outbreaks, or
      other demographic collapses. To predict recolonization and understand dispersal
      capacity in a stream-breeding frog, we examined individual movement patterns and
      gene flow among four subpopulations of the Neotropical glassfrog, Centrolene
      prosoblepon, at a mid-elevation cloud forest site at El Cope, Panama. We measured
      male movement directly during a two year mark-recapture study, and indirectly
      with gene flow estimates from mitochondrial DNA sequences (mtDNA). Individuals of
      this species showed strong site fidelity: over two years, male frogs in all four
      headwater streams moved very little (mean = 2.33 m; mode = 0 m). Nine individuals
      changed streams within one or two years, moving 675-1,108 m. For those males
      moving more than 10 m, movement was biased upstream (p < 0.001). Using mtDNA ND1
      gene sequences, we quantified gene flow within and among headwater streams at two
      spatial scales: among headwater streams within two adjacent watersheds (2.5 km2)
      and among streams within a longitudinal gradient covering 5.0 km2. We found high
      gene flow among headwater streams (phi(ST) = 0.007, p = 0.325) but gene flow was
      more limited across greater distances (phi(CT) = 0.322, p = 0.065), even within
      the same drainage network. Lowland populations of C. prosoblepon potentially act
      as an important source of colonists for upland populations in this watershed.

PMID- 18624226
TI  - [Phytoplankton from Tehuantepec River, Oaxaca, Mexico and some biogeographical
      relationships].
AB  - Phytoplankton species collected from the limnetic to euryhaline sections of
      Tehuantepec River were identified, classified and compared with regional
      information from Mexico and South America. We collected 15 samples every three
      months from July 1997 through August 1998 with a 20 microm net and a Van Dorn
      bottle. Indicator values and a code checklist are included. A total of 58
      families, 121 genera, 273 species, one subspecies, 75 varieties, 13 forms and one
      morphotype were identified in the taxa Bacillariophyta (42.0 %), Chlorophyta
      (29.0 %), Cyanoprocaryota (18.0 %), Euglenophyta (5.0 %), Dinophyta (3.0 %),
      Cryptophyta (2.0 %) and Chrysophyta (1.0 %). The predominant families were
      Scenedesmaceae (24 species), Oocystaceae (22), Bacillariophyceae (21),
      Chaetocerotaceae (15) and Euglenaceae (14). Five families, eight genera, 72
      species, 45 varieties and eight forms are first records for Mexico. The species
      Chroococcus turgidus, Microcystis flosaquae and Pseudanabaena limnetica (which
      produce massive blooms or red tides) are important in this river of moderate
      water quality.

PMID- 18624227
TI  - Spatial and temporal variations of meiofaunal communities from the western sector
      of the Gulf of Batabano, Cuba: II. Seagrass systems.
AB  - The meiofauna from seagrass meadows in the western sector of the Gulf of
      Batabano, Cuba were studied to describe the spatial and temporal variations in
      community structure. Replicated cores were taken in three locations (arranged in
      m- and km-scales) and in two seasons (dry and wet). The meiofauna (metazoans
      between 500 and 45 microm) were identified to major taxa. Temporal changes in the
      meiofaunal communities could not be detected and they are not linked to the
      subtle seasonal changes in the water column. A larger variation in community
      structure was observed in the spatial m-scale (among cores in a station) probably
      accredited to heterogeneity of microenvironment and biological processes. A
      second source of variation in the km-scale (among locations) was identified
      relating to physical processes affecting seagrass meadows: marine currents and
      anthropogenic disturbances. Distribution patterns of meiofauna across locations
      coincide with one study from 20 years ago in seagrass beds (i.e. higher densities
      in area closer to break-shelf and diminution of fauna at southern of Pinar del
      Rio); however, cumulative anthropogenic disturbances on seagrass meadows would
      most likely explain the depletion of communities observed in our survey in
      comparison with decades ago. Estimates of meiofaunal density and richness of
      major taxa from our study (and other areas from the Cuban shelf) are consistently
      lower than other temperate and tropical sites; possibly caused by low primary
      productivity due to narrow tidal amplitude and oligotrophic waters.

PMID- 18624228
TI  - [Effects of a submarine discharge of urban waste on octocoral (Octocorallia:
      Alcyonacea) communities in Cuba].
AB  - The composition and structure of octocoral communities on coral reefs close to a
      submarine outfall were studied at Reparto Flores, west of Havana City, Cuba.
      Octocoral community changes after the deployment of the submarine outfall in 2000
      were monitored from June 2002 to September 2005, taking as baseline the data
      existing before its construction. The area also receives the influence of the
      polluted river Quibu that passes through a great part of the west side of the
      City. Sampling was done by means of SCUBA diving, counting and identifying
      colonies in situ within a 1 m2 frame that was randomly placed as many times as to
      warrant stabilized values of Shannon and Weaver's heterogeneity index H'. In
      agreement with the available hydrochemical information, changes in the diversity
      indexes (Shannon and Weaver's heterogeneity index H', Pielou's equitability index
      J', and Margalef's species richness index R1), the Herrera-Moreno's comparative
      pollution index (ICC), and density of some octocoral species at a depth of 10 m
      suggest a decrease in the influence of polluters from 1989 to 2005. Nevertheless,
      these indicators were affected in 2004 by a sudden intense but brief colonization
      of Briareum asbestinum, a species that is not typical of polluted places. At a
      depth of 20 m, a co-dominance of Plexaura kuekenthali and Eunicea clavigera
      (resistant and non resistant to pollution, respectively) and an increase of the
      comparative pollution index (ICC) was observed. The increase of P. kuekenthali, a
      pollution indicator, suggests a rise in the pollution effect 20 m in depth,
      because of the recent impact caused by the greater closeness of the outfall mouth
      50 m deep. Results corroborate the hypothesis about the pollution indicator
      character of P. kuekenthali. However, this could not be explored for Eunicea
      flexuosa (also considered a pollution-indicator) due to an intensive illegal
      selective extraction for lucrative handicraft purposes, which led to a remarkable
      decrease in its density. B. asbestinum and E. clavigera were outlined as poorly
      resistant to pollution.

PMID- 18624229
TI  - [Latin American malacology. Freshwater mollusks from Argentina].
AB  - A report and an updated list with comments on the species of freshwater molluscs
      of Argentina which covers an area of 2 777 815 km2 is presented. Distributions of
      Gastropoda and Bivalvia families, endemic, exotic, invasive as well as entities
      of sanitary importance are also studied and recommendations on their conservation
      are provided. Molluscs related to the Del Plata Basin have been thoroughly
      studied in comparison to others areas of the country. This fauna exhibits
      relatively the biggest specific richness and keeps its affinity with the fauna of
      other regions of the basin in areas of Paraguay and Brasil. The 4 500 records of
      molluscs considered in this paper arise from the study of the collections of
      Museo Argentino de Ciencias Naturales "Bernardino Rivadavia", Buenos Aires; Museo
      de La Plata, La Plata and Fundacion "Miguel Lillo", Tucuman. These institutions
      keep very important collections of molluscs in southern South America. Field
      information has recently been obtained and localities cited by other authors are
      also included in the data base. Until today, 166 species have been described, 101
      belonging to 10 families of Gastropoda and 65 to 7 of Bivalvia. Families with
      highest specific richness are Lithoglyphidae (22) and Sphaeriidae (25),
      respectively. The number of endemic species (those present only in Argentina) by
      family is: Gastropoda: Ampullariidae (1), Cochliopidae (10), Lithoglyphidae (11),
      Thiariidae (3), Chilinidae (11), Lymnaeidae (2) and Physidae (2?); Bivalvia:
      Hyriidae (1?); Etheriidae (1?) and Sphaeriidae (10). Families with a distribution
      that comprise almost the whole country are: the Sphaeriidae and the gastropods
      Cochliopidae, Chilinidae and Lymnaeidae. Families Erodonidae and Solecurtidae
      (Bivalvia) were registered in mixohaline environments from Buenos Aires province.
      Gastropod families Thiaridae and Glacidorbiidae show a very restricted
      distribution. The rest of the families are present mainly in the center and north
      of the country. Species of sanitary interest are the propagators of:
      schistosomiasis -Biomphalaria peregrina, B. straminea y B. tenagophila,
      Planorbidae-, fasciolasis -Lymnaea viatrix and L. columnella, Lymnaeidae- and
      dermatitis -Chilina gibbosa and C. fluminea, Chilinidae. Invasive species are:
      Corbicula fluminea (Corbiculidae) and Limnoperna fortunei (Mytilidae). The
      construction of new areas for the protection and conservation of the high risk
      endemic species of freshwater molluscs is a priority. It is necessary to give
      special attention to the species of the patagonic mountain range and of the
      mesopotamic area of the Del Plata Basin.

PMID- 18624230
TI  - Comparison of gastropod mollusc (Apogastropoda: Hydrobiidae) habitats in two
      crater lakes in Nicaragua.
AB  - The aquatic gastropod mollusc, Pyrgophorus coronatus, may perform an important
      role in the transmission of an emergent ocular pathology among fishes in Lake
      Apoyo, Nicaragua. This disease emerged after an introduction of tilapia
      (Oreochromis niloticus) and the subsequent loss of Chara sp. beds in the lake. We
      compared the mollusc population densities in three habitats (sandy/muddy
      substrates, rocks, and Chara vegetation) at varying depths (1.5, 10, 20, and 30
      m) in two volcanic crater lakes in Nicaragua: Lake Apoyo and Lake Xiloa. where
      lower numbers of affected fishes were found and tilapia has not been introduced.
      Duplicate samples at 1.5 m depth were taken in each habitat monthly for a year,
      and triplicate samples for bathymetric analysis of snail populations were
      performed during August, 2005. Samples of fixed surface area were filtered in a
      0.4 cm size screen and live snails were counted from each sample. The preferred
      snail habitat in both lakes, Chara beds, was vastly reduced in Lake Apoyo via
      consumption by introduced Nile tilapia (Oreochromis niloticus). Structureless
      sandy substrates (mean +/- standard error 3.1+/-1.3 ind/m2) had lower population
      densities than other habitats in Lake Xiloa (rocks 590.9+/-185.3 ind/m2;
      vegetation 3 686.5+/-698.2 ind/m2; ANOVA 1, p<0.01 in both cases) but this
      difference was attenuated in Lake Apoyo (sand 384.4+/-111.1 ind/m2; rocks 1
      480.4+/-384.8 ind/m2: 0.0 1<p<0.05), where the snails on sandy bottoms were
      mostly embedded in filamentous algae coating this substrate. Snail population
      densities in Chara were lower at 20 m than more shallow depths in both lakes.
      Chara was not found at 1.5 m depth in Lake Apoyo, and was not present at 30 m
      depth in either lake. Shell lengths in rocky substrate in Lake Apoyo (3.62+/-0.12
      mm) were greater than in Lake Xiloa (2.39+/-0.12 mm), suggesting differential
      snail predation levels in the lakes (p<0.005). Snail populations increased by 67
      % inside exclusion cages in sandy substrates in Lake Apoyo (paired t-test,
      p<0.05), demonstrating the importance of foraging pressure on snail populations.
      Snail populations in open cages, on the other hand, were reduced by 23 %
      (p<0.05), suggesting the importance of subacuatic structure in feeding areas for
      molluscivorous fishes. We found a significant preference toward Chara by the
      snails (p<0.05) and significant foraging pressure on them (p<0.05) in sandy/muddy
      substrates. The disruption of Chara by introduced tilapias in Lake Apoyo may play
      a role in the emergence of ocular pathologies in the lake.

PMID- 18624231
TI  - Reproductive and larval cycle of the scallop Argopecten purpuratus (Ostreoida:
      Pectinidae), during El Nino-La Nina events and normal weather conditions in
      Antofagasta, Chile.
AB  - Seasonality, amplitude, and magnitude of spawning events were determined for
      Argopecten purpuratus in the La Rinconada marine reserve, Antofagasta, Chile,
      between December 1995 and January 2004. During the same period, samples of
      scallop larvae were obtained in vertical plankton hauls recovered within this
      reserve in an area routinely exposed to circular, gyre-like currents which helped
      retain the larvae within the bay. The reproduction of this population in normal
      or cool (e.g. "La Nina", 1998-2000) years occurred throughout the year, with a
      more active period between September and April, declining in June and August;
      this contrasted with the warmer "El Nino" oceanographic period of 1997-98 in
      which reproductive activity was more intense and prolonged throughout the entire
      year. The reproductive events in this population were mostly synchronous,
      although one asynchronous period occurred each year following the more intense
      March to May spawnings. This reproductive activity generated a continuous
      presence of larvae in the area in which no strict relation could be found between
      the intensities of spawning and numbers of larvae in the water. Larval presence
      was, however, generally correlated with active spawning periods. Important
      increases in larval numbers recorded at the end of 1999 and the beginning of 2003
      were correlated with census data showing a higher percentage presence of
      broodstock over 90 mm in shell length during these years. An adequate stock of
      this size class is needed for a successful seed capture program in the reserve
      (for mass culture).

PMID- 18624232
TI  - The fish species composition and variation of catch from the small-scale gillnet
      fishery before, during and after the 1997-1998 ENSO event, central Mexican
      Pacific.
AB  - In the tropical and subtropical coastal zone, were highly diverse fish
      communities occur, it is important to study the small scale fisheries exploiting
      these communities. For this study, 219 fishing days were carried out in Bahia de
      Navidad, Jalisco, Mexico. Four gillnets with different mesh sizes (76.2, 88.9,
      101.6 and 114.3 mm) were used for the fishing operations, from April 1994 to
      March 1995 and from January 1998 to December 2000. A total of 26126 organisms
      weighting 11680 kg were caught. One hundred and eighty three species belonging to
      57 families and 19 orders were identified. Ten species accumulated more than 60%
      of the total abundance and biomass, the remaining species (173) individually
      contributed with less than 2% of the total abundance and biomass. The most
      important species in the catch were Microlepidotus brevipinnis, Caranx caballus,
      Haemulon flaviguttatum, Scomberomorus sierra, C. caninus, C. sexfjasciatus,
      Lutjanus guttatus and L. argentiventris. The catch per unit of effort showed a
      large variation during the study, both in number and biomass. On average, 110
      fishes and 48.5 kg fishing day(-1) were caught. The maximum values were recorded
      during January and October 1998 (250 fishes and 100 kg fishing day(-1)), and the
      minimum values were recorded during September and November 1994 (25 org. and 10
      kg fishing day(-1)). The total abundance and biomass was lower during the 1994-95
      period (F=6.16, 8.32, P<0.05). There were statistically significant differences
      among the annual catch from each gillnet. All the environmental changes caused by
      the ENSO event had ecological and economic effects that can be rated from
      moderate to severe.

PMID- 18624233
TI  - [Reproduction of the fish Gymnothorax equatorialis (Pisces: Muraenidae) in
      Jalisco and Colima, Mexico].
AB  - Reproduction of the fish Gymnothorax equatorialis (Pisces: Muraenidae) in Jalisco
      and Colima, Mexico. A total of 707 Gymnothorax equatorialis were collected
      monthly in the Jalisco and Colima coast, Mexico, from December 1995 to December
      1998 and from August to November 1999, in order to determine their reproduction
      patterns. Females outnumbered and had longer bodies (mean length 54.7 cm) than
      males (52.1 cm). The minimum, maximum and mean values of total fecundity were
      respectively 9 660, 99 992 and 32 029 eggs. The total body length at which 50
      percent of individuals have ripe gonads (L50) was 43.7 cm for females and 42.7 cm
      TL for males. Ovaries had two main types of oocytes: small inmature in cromatin
      nucleolus phase (85.1 microm) and large mature in secundary vitellogenesis phase
      (701.6 microm). High numbers of spermatozoa were observed in the seminal tubes of
      ripe testicles, which presented a lobular development. Based in gonad features
      and temporal changes in the gonad-somatic index, it is concluded that G.
      equatorialis has two relatively short reproduction periods (at the middle and at
      the end of the year).

PMID- 18624234
TI  - Panbiogeographical analysis of Costa Rican freshwater fishes.
AB  - Track analysis and Parsimony analysis of endemicity (PAE) were performed to
      analyze the distribution pattern of Costa Rican freshwater fishes. A basic matrix
      (presence/absence) was prepared using the distribution of 77 freshwater fish. The
      data were analyzed with CLIQUE software in order to find generalized tracks
      (cliques). Data also were analyzed with the software NONA and Winclada version
      1.00.08 in order to perform the Parsimony Analysis of Endemicity (PAE). Fourteen
      equally probable cliques were found with 31 species in each and the intersection
      of the amount was selected as a generalized track dividing the country in two
      main zones: Atlantic slope from Matina to Lake Nicaragua and Pacific slope from
      the Coto River to the basin of the Tempisque River connected with some branches
      oriented to the central part of the country. PAE analysis found ten cladogram
      areas (72 steps, CI=0.45, RI=0.64), using the "strict consensus option" two
      grouping zones were identified: Atlantic slope and Pacific slope. Both PAE and
      Track Analysis show the division of the two slopes and the orientation of the
      generalized track suggests new biogeographical evidence on the influence of both
      old and new southern elements to explain the migrations of freshwater fish into
      Central America during two different geological events.

PMID- 18624235
TI  - Growth of the Pacific jack Caranx caninus (Pisces: Carangidae) from the coast of
      Colima, Mexico.
AB  - The Pacific jack Caranx caninus is a common species fished by artisanal fishermen
      off the coast of Colima, Mexico. During 2002, monthly samples of morphometric
      data and otoliths were taken to determine age and growth. Seven age groups were
      identified. The highest growth, 14.4 cm, takes place during the first year of
      life. During the second year, C caninus grows 11.76 cm; the third year 9.61 cm;
      the fourth 7.85 cm; the fifth 6.41 cm and sixth year 5.24 cm. The constants of
      von Bertalanffy's growth equation were: L(infinity) = 83.26 cm, W(infinity) =
      18.138 g, K = 0.202, t(0) = -0.283 and A(0.95) = 15 years. Growth curves of other
      species of the same genus were calculated in order to compare them with the one
      obtained in the present work. The gonadosomatic index presented higher values
      during November and May. The periods of more intensive feeding are from August to
      February.

PMID- 18624236
TI  - Mesobathic chondrichthyes of the Juan Fernandez seamounts: are they different
      from those of the central Chilean continental slope?
AB  - We compared the geographic distribution of groups of chondrychthid fishes of two
      physically proximal, although geographically different, regions that include the
      Juan Fernandez seamounts and the central Chilean continental slope, both sampled
      at mesopelagic and mesobenthonic depths. The ridge is in the Nazca Plate, while
      the slope region in on the South American Plate, and is closer to the South
      American continent. We found six species of Chondrichthyes for the seamounts
      (four orders, four families). The slope sampling produced ten species of
      Chondrichthyes, of which Torpedo tremens De Buen 1959, was the only species in
      common with the Juan Fernandez area. There are clear differences between the
      Chondrichthyes of the two regions. These fisheries require adequate
      administrative modes.

PMID- 18624237
TI  - A new quantitative classification of ecological types in the bromeliad genus
      Tillandsia (Bromeliaceae) based on trichomes.
AB  - Using collection specimens, we measured the density and wing area of trichomes in
      37 species of the bromeliad genus Tillandsia, specifically the abaxial proximal,
      abaxial distal, adaxial proximal and adaxial distal parts of the leaf. The
      product of the trichome "wing" area by the number of trichomes (means) produced a
      pure number (T) that was correlated to ecological features. The correlation was
      positive with respect to arid environments (xeric Tillands) and negative with
      respect to humid environments (mesic Tillands). Bulbous, and particularly
      myrmecophytic species and species with tanks, represented particular categories.
      Other intermediate types were identified based on the T number, totalling five
      ecological types. In comparison with other systems of ecological typification for
      Tillands and other Bromeliaceae, the present system offers measurable data whose
      analysis is reproducible.

PMID- 18624238
TI  - Potential role of frugivorous birds (Passeriformes) on seed dispersal of six
      plant species in a restinga habitat, southeastern Brazil.
AB  - Restingas are considered stressful habitats associated with the Brazilian
      Atlantic forest, and their ecological interactions are poorly known. The goal of
      the present study was to determine the potential role of frugivorous birds as
      seed dispersers in a restinga habitat. Data were collected in Parque Nacional da
      Restinga de Jurubatiba, southeastern Brazil, where the main physiognomy (Open
      Clusia Formation) is characterized by the presence of patches of vegetation
      covering 20 to 48 % of the sandy soil and reaching a height of 5 m. Birds were
      captured with mist nets (12 x 2.5 m; 36 mm mesh; 1,680 net-hrs) and had their
      fecal and regurgitate samples inspected for seeds. Six plant species found in
      these bird samples were studied. The germination of seeds obtained from plants
      was compared to those from the birds. Both groups of seeds were set on Petri
      dishes at room temperature and washed when infected with fungi. In general, there
      was no effect on germination rate, and the effect on germination speed was
      negative. Germination of seeds from Pilosocereus arrabidae treated by the birds
      seemed to be influenced by storage of defecated seeds, while few Miconia
      cinnamomifolia seeds both from plants and from birds germinated. Ocotea notata
      presented a great variation in time to the onset of germination, perhaps an
      advantage against dissecation. Aechmea nudicaulis, Clusia hilariana and
      Erythroxylum subsessile probably take advantage of the arrival to favorable
      microhabitats, not by the gut effect on the seeds. All plant species studied are
      numerically important for the community and some of them are main actors in the
      succession of vegetation patches. Among the birds, Mimus gilvus is an important
      resident species, endemic to restingas in Brazil, while Turdus amaurochalinus is
      a visitor and may be important for plants that fructify during its passage by the
      study site. Although the effect of pulp removal was only tested for one species
      (Achmea nudicaulis) in the present study, we confirmed that the tested effect of
      restinga frugivorous birds on seed germination was generally null. Although there
      is a need for more detailed studies on specific animal-plant interactions on this
      habitat, the overall effect of the birds on seed dispersal in restinga is
      probably positive.

PMID- 18624239
TI  - [Genetic diversity and kin relationships among wild and cultivated populations of
      the pejibaye palm (Bactris gasipaes, Palmae) using microsatellite markers].
AB  - Genetic diversity and kin relationships among wild and cultivated populations of
      the pejibaye palm (Bactris gasipaes, Palmae) using microsatellite markers. The
      genetic diversity of the peach palm (Pejibaye, Bactris gasipaes Kunth) was
      evaluated using four nuclear DNA microsatellites in an effort to elucidate the
      evolution and domestication of this crop. A total of 258 samples from seven wild
      populations and eleven races were analyzed. All loci were polymorphic and a total
      of 50 alleles were identified. Average genetic diversity (0.67) and genetic
      differentiation among populations (Fst=0.16) were high when all populations were
      considered. Genetic differentiation was lower when the populations were grouped
      according to their origin into Western and Eastern populations (Fst=0.13 for
      both). Gene flow was slightly higher among Western populations (Nm=1.71) than
      among Eastern populations (Nm=1.62). The Putumayo, Yurimaguas, Vaupes, Tucurrique
      and Guatuso races seem to have been subjected to intense human selection. Hybrid
      populations exist in Azuero, Tuira, Cauca, Vaupes, Puerto Ayacucho and Solimoes,
      probably resulting from exchange and introgressions among sympatric wild and
      cultivated populations. Genetic distance (Dm) was estimated to determine the
      degree of relationship among populations using the neighbor-joining method; the
      wild populations from Maracaibo were used as the outgroup. The populations were
      divided into three general groups: Maracaibo (B. caribaea, B. macana var veragua
      and B. macana var arapuey), Eastern Amazon (Tembe, Para and Acre) and a third
      group with two subgroups, Western (Azuero, Chontilla, Tuira, Cauca, Tucurrique
      and Guatuso) and Upper Amazon (B. dahlgreniana, Puerto Ayacucho, Solimoes, Vaupes
      and Putumayo). The genetic relationships strongly support the hypothesis that
      peach palm was brought into cultivation independently in no less than three
      areas: the Western Andes (extending into lower Central America); Upper Amazon
      (extending into the Solimoes and its tributaries), and the Eastern Amazon
      (extending from Bolivia to the lower Amazon through the Madeira River).

PMID- 18624240
TI  - [Population structure and environmental relationships of the tropical tree
      Nectandra rudis (Lauraceae), a rare species in western Mexico].
AB  - Population structure and environmental relationships of the tropical tree
      Nectandra rudis (Lauraceae), a rare species in western Mexico. The tree N. rudis
      is a rare species from western Mexico of which community and population features
      are unknown. We studied a population in an altitudinal gradient, from 550-1,850 m
      above sea level in the Sierra de Manantlan, Jalisco, Mexico. We established four
      60x48 m sample sites at vertical distances of 100 m along this altitudinal
      gradient. Within each plot, ten 100 m2 circular sub-sampling units were randomly
      located. At each unit, we recorded diameter at breast height (dbh) and tree
      height for all woody vegetation > or =2.5 cm dbh. Basal area, tree density,
      frequency, species richness and importance values per species and plot. We
      estimated the vertical structure (total tree height) and diameter( as
      M=5log(10)N) for all N. rudis individuals. A direct ordination through Canonical
      Correspondence Analysis was done, involving amongst other species, edaphic and
      environmental data matrices. The record of 44 N. rudis individuals, in seven out
      the 56 plots sampled, represents the most septentrional record for the species
      and the first in Western Mexico. Its density and basal area represented 4.5 % and
      8.7 % respectively of the total estimated for the community. The greatest
      importance values were observed at 1 650 m above sea level. The population
      structure of N. rudis is structured into five diameter categories in an inverse
      "J" shaped distribution. This is a typical behavior observed to occur in the
      Lauraceae, which produces big seeds of short viability that germinate when there
      is high soil moisture content. The species tend to form dense seedling banks
      although only a reduced number of them are able to survive. Species richness
      varies from 27 to 39 at plot level; the greatest importance values for the plots
      on which N. rudis was found, corresponds to Urera verrucosa (Liebm.) V.W.
      Steinm., N. rudis, Ficus sp., Beilschmiedia manantlanensis Cuevas y Cochrane,
      amongst others. Canonical Correspondence Analysis suggests that environmental
      variables such as rooted trees, crown cover, litter depth and soluble magnesium
      are the more significant explanatory variables for the distribution and abundance
      of N. rudis.

PMID- 18624241
TI  - Do seasonal changes in light availability influence the inverse leafing phenology
      of the neotropical dry forest understory shrub Bonellia nervosa
      (Theophrastaceae)?
AB  - In tropical dry forests most plants are deciduous during the dry season and flush
      leaves with the onset of the rains. In Costa Rica, the only species displaying
      the opposite pattern is Bonellia nervosa. To determine if seasonal changes in
      light availability are associated with the leaf and reproductive phenology of
      this species, we monitored leaf production, survival, and life span, as well as
      flower and fruit production from April 2000 to October 2001 in Santa Rosa
      National Park. Leaf flushing and flower bud production took place shortly after
      the autumnal equinox when day length starts to decrease. Leaves began expansion
      at the end of the wet season, and plants reached 70 % of their maximum leaf area
      at the beginning of the dry season, maintaining their foliage throughout the
      entire dry period. Leaf shedding occurred gradually during the first three months
      of the wet season. Leaf flushing and shedding showed high synchrony, with leaf
      numbers being related to light availability. Maximum leaf production coincided
      with peaks in radiation during the middle of the dry season. Decreasing day
      length induces highly synchronous flower bud emergence in dry forest species, but
      this is the first study indicating induction of leaf flushing by declining day
      length.

PMID- 18624242
TI  - Propagules of arbuscular mycorrhizal fungi in a secondary dry forest of Oaxaca,
      Mexico.
AB  - Plant cover loss due to changes in land use promotes a decrease in spore
      diversity of arbuscular mycorrhizal fungi (AMF), viable mycelium and, therefore,
      in AMF colonization, this has an influence in community diversity and, as a
      consequence, in its recovery. To evaluate different AMF propagules, nine plots in
      a tropical dry forest with secondary vegetation were selected: 0, 1, 7, 10, 14,
      18, 22, 25, and 27 years after abandonment in Nizanda, Oaxaca, Mexico. The
      secondary vegetation with different stages of development is a consequence of
      slash and burn agriculture, and posterior abandonment. Soil samples (six per
      plot) were collected and percentage of AMF field colonization, extrarradical
      mycelium, viable spore density, infectivity and most probable number (MPN) ofAMF
      propagules were quantified through a bioassay. Means for field colonization
      ranged between 40% and 70%, mean of total mycelium length was 15.7 +/- 1.88 mg(
      1) dry soil, with significant differences between plots; however, more than 40%
      of extracted mycelium was not viable, between 60 and 456 spores in 100 g of dry
      soil were recorded, but more than 64% showed some kind of damage. Infectivity
      values fluctuated between 20% and 50%, while MPN showed a mean value of 85.42 +/-
      44.17 propagules (100 g dry soil). We conclude that secondary communities
      generated by elimination of vegetation with agricultural purposes in a dry forest
      in Nizanda do not show elimination of propagules, probably as a consequence of
      the low input agriculture practices in this area, which may encourage natural
      regeneration.

PMID- 18624243
TI  - Reproductive biology of Hechtia schottii, a dioecious Bromeliaceae, in Mexico.
AB  - Hechtia schottii is a terrestrial, rosetofilous, dioecious, polycarpic succulent
      herb, that grows mainly in shrubby associations, and less frequently, in
      secondary low caducifolious forests, both on calcareous soils or limestone
      outcrops in Yucatan and Campeche States, Mexico. We studied phenology, floral and
      pollination biology, and breeding system at Calcehtok, Yucatan, during two
      flowering seasons. Plants bloom mainly during the dry season (November-April) and
      disperse seeds during the rainy season (May-October). Both floral morphs have
      diurnal anthesis; pollen is removed ca. 1 h after anthesis starts and both floral
      morphs are visited by several insect species, especially bees, but results
      suggest that the introduced honey bee, Apis mellifera, is the pollinator.
      Controlled crossings show that the species is functionally dioecious and requires
      to be serviced by pollinators based on fruit setting only in unassisted cross
      pollination crosses.

PMID- 18624244
TI  - [Control in vitro tick (Boophilus microplus; Acari: Ixodidae) through plant
      extracts].
AB  - Control in vitro tick (Boophilus microplus; Acari: Ixodidae) through plant
      extracts. Hydro-alcohol extracts of ten tropical plants were tested by the
      immersion method on mature ticks (Boophilus microplus Canestrini 1887). The
      biological evaluation was made with raw hydro alcoholic extracts (R-OH) to
      determine the most promissory compounds, which later were fractioned in their
      polar and non-polar parts. The polar parts showed a significantly inferior
      effect. The species that produced the highest mortality were Zizigium aromaticum,
      Morus alba, Piper nigrum and the mixture of Allium sativum- Z. aromaticum (all
      non-polar); on oviposition: M. alba, P. nigrum and the mixture of A. sativum - Z.
      aromaticum (all non-polar); on eclosion: P. nigrum, Z. aromaticum, Echinacea
      angustiofilia, Poligonum punctatum, M. alba and the mixture of A. sativum-Z.
      aromaticum (all non-polar): on control percentage: P. nigrum, E. angustifolia, P.
      punctatum and M. alba (all non-polar, except for M. alba in which both fractions
      showed important activity); and finally, on the percentage of oviposition
      inhibition: P. nigrum, E. angustifolia, P. punctatum, Gliricidia sepium and M.
      alba.

PMID- 18624245
TI  - [Anthropoentomophagic biodiversity of the Zongolica region, Veracruz, Mexico].
AB  - Anthropoentomophagic biodiversity of the Zongolica region, Veracruz, Mexico.
      During two and a half years (2003-2005) we recorded the insect species used as
      food at Zongolica, Veracruz State, Mexico. Interviews were made among people
      (200) of this municipality to know which insects they consumed. The total of
      registered species was 57 (Orthoptera, Hemiptera, Homoptera, Megaloptera,
      Coleoptera, Lepidoptera and Hymenoptera). The Orthoptera was the most frequently
      ingested. Twenty-four of these species were new records for edible insects of
      Mexico. They are eaten in immature stages or as adults, generally only roasted.
      Consumption is seasonal. Some species are commercialized in the "tianguis"
      (little town markets) and/or in the larger Zongolica market. There is a
      "protoculture" of three species, one cockroach (Periplaneta australasiae
      Fabricius) and two moths (Latebraria amphipyroides Guenee and Arsenura armida
      armida Cramer). In Zongolica, anthropoentomophagy is an ancestral habit.

PMID- 18624246
TI  - [Diversity of terrestrial gastropod mollusks in the Pacific region of Nicaragua,
      and their habitat preferences].
AB  - Diversity of terrestrial gastropod mollusks in the Pacific region of Nicaragua,
      and their habitat preferences. Landsnail communities of the Nicaraguan Pacific
      Slope were studied. The study area was subdivided into 21 quadrats (ca. 40 x 40
      km). A high taxonomic richness was found: 79 species, 43 genera and 23 families.
      Species richness (S) per quadrat ranged from 17 through 50. The biogeographic
      index presented higher values on quadrats 5 (3.04), 6 (3.03), 8 (2.96) and
      11(2.96). Quadrat 11 had the highest species richness (S=50), and one of the
      highest biogeographic index values (IB=2.96). Gastropod mollusk communities are
      favored by sites with an illumination of filtered sun, associated to riparian
      forests and with a susbtratum of wet soils and leaf litter.

PMID- 18624247
TI  - Effects of dietary calcium on growth and oviposition of the African land snail
      Limicolaria flammea (Pulmonata: Achatinidae).
AB  - In an attempt to elucidate the role of calcium in the life of the edible
      Achatinid snail, Limicolaria flammea (Miller) I investigated short and long term
      effects of calcium added to the food. The short term experiments lasted for 18,
      30 and 32 weeks respectively, while the long term experiment to determine life
      time utilization of calcium carbonate lasted for 15 months. In the short term
      experiments, hatchlings were divided into densities of one, ten and 50 snails. In
      the 10 snail group, there was a positive correlation between calcium provision,
      body weight (t test, p < 0.01; r = 0.96, p < 0.0001) and shell length (t test, p
      < 0.01; r = 0.96, p < 0.00001). There was also a positive correlation between
      increase in shell length and availability of calcium in the 1 snail group (t
      test, p< 0.01; r = 0.99, p < 0.00001). In the 50-snail group, the correlation was
      positive for shell length of the snails (t test, p < 0.05; r = 0.99, p < 0.0001)
      and body weight (t-test, p < 0.05; r = 99, p < 0.00001). Mortality was very high
      in the snails deprived of calcium and they did not produce eggs. In the long term
      experiment, there were three feeding peaks in L. flammea. In the first feeding
      peak, amount of food and calcium ingested by the snails increased in the first
      three months of life. The second feeding peak occurred at six months of age,
      while the last occurred at 10 months of age. The amount of calcium ingested
      during the second peak decreased gradually in the 4th and 5th month. The amount
      of calcium ingested was lowest during the 3rd feeding peak. The period of highest
      weight gained by the snails was between the 1st and 6th month and then dropped at
      between six and 12 months of age which corresponds to the period of egg
      production. There were also three peaks of egg production; the first was between
      six and eight months (535 eggs), the second at between 10 and 11 months (350
      eggs) and the third at 13 to 14 months (310 eggs) respectively.

PMID- 18624248
TI  - The annual life history of a population of the aquatic Coleopteran Derallus
      angustus (Coleoptera: Hydrophilidae).
AB  - Derallus Sharp, 1882 is a Neotropical genus of aquatic coleopterans that belongs
      in the tribe Berosini and includes 15 species. D. angustus Sharp is widely
      distributed from Guatemala to Argentina. The population dynamics of this species
      was studied by periodic sampling of a natural population from the southernmost
      Subtropical Domain of the Neotropical Region. The study site was near Punta Lara
      (34 degrees 47' S, 58 degrees 01' W; Ensenada, Buenos Aires province, Argentina).
      Twenty seven samples consisting of 20 units of aquatic vegetation (200 cm2 each)
      were taken during one year. Larvae and adults were removed from the vegetation
      and counted (pupae were not studied). There was a peak of first instar larvae
      abundance at the end of spring, and another at the end of summer. Adults and
      third instar larvae were present throughout the whole year. The population is
      interpreted as being univoltine and including two periods of enhanced
      reproductive activity.

PMID- 18624249
TI  - [Growth of the Orinoco Caiman (Crocodylus intermedius, Crocodylia: Crocodylidae)
      under two captivity conditions].
AB  - Growth of the Orinoco Caiman (Crocodylus intermedius, Crocodylia: Crocodylidae)
      under two captivity conditions. In order to determine the growth of Caiman of the
      Orinoco (Crocodylus intermedius) under two conditions of captivity, 40 specimens
      were raised during 11 months and 15 days in two circular tanks, with 28.3 m2 of
      surface area and a volume of 62.2 m3 in each tank. The tanks were built with
      concrete walls and guarded blocks covered internally with sheets of myrrhlike
      resin, and a roof of galvanized sheets. One tank was covered partially with the
      galvanized sheets (tank I), the other was totally covered (tank II). Twenty
      caimans were placed in each tank, and both groups were fed with 85% beef, 10%
      fresh fish, 5% hen eggs and a mixture of minerals and vitamins. The length and
      weight differed significantly between the groups (p < 0.001). Mean growth (103.0
      +/- 6.81 cm) and weight (3 987 +/- 0.98 g) were higher in tank II, (tank I: 88.9
      +/- 7.58 cm; 2 705 +/- 0.69 g). The greater growth in tank II reflects higher air
      and water temperatures. The survival rate was 97.5%. These results can be used
      for rearing caimans in captivity for conservation and commercial purposes.

PMID- 18624250
TI  - [Richness and abundance of birds in riparian forest belts of varied breadths at
      the Sesesmiles river microwatershed, Copan, Honduras].
AB  - Richness and abundance of birds in riparian forest belts of varied breadths at
      the Sesesmiles river microwatershed, Copan, Honduras. Riparian forests protect
      many species of plants and animals. We studied bird communities in riparian
      forest belts of the Sesesmiles river microwatershed, Copan, Honduras (140 degrees
      43' 12" - 140 degrees 58' 35" N, 88 degrees 53' 23" - 89 degrees 14' 17" W). The
      main goal was to explore the effects of belt breadth on the richness and
      abundance of avian species visiting these forests. We selected 20 belts, and
      randomly established 30 observation points to monitor bird presence in the dry
      (March-April 2005) and rainy (June-July 2005) season (N= 60 observations). A
      total of 1,294 birds belonging to 145 species were recorded. Bird diversity was
      significantly correlated to the breadth of the riparian belts, with a greater
      number of species and individuals in belts 50 m wide or wider. Insectivorous and
      nectarivorous birds were the most abundant guilds. All bird species identified
      depend to some degree on riparian forests and are affected by belt breadth.
      Riparian belts over 50 m should be kept or established in order to conserve bird
      populations within agricultural and fragmented landscapes in similar tropical
      areas.

PMID- 18624251
TI  - [Community structure and association of waterbirds with spatial heterogeneity in
      the Bahia Magdalena-Almejas wetland complex, Baja California Sur, Mexico].
AB  - Community structure and association of waterbirds with spatial heterogeneity in
      the Bahia Magdalena-Almejas wetland complex, Baja California Sur, Mexico. To test
      the hypothesis that spatial heterogeneity determines waterbird diversity in a
      coastal wetland, we compared waterbird density, diversity, and species
      composition among various habitats and landscapes units in Bahia Magdalena
      Almejas, Baja California Sur, Mexico. Based on diversity patterns and bird
      distribution, we assessed the effect of coastal development on the waterbird
      community structure. To gather information on habitat features and waterbird
      populations we conducted waterbird censuses in 329 habitat segments along the
      internal coastline of the study area, from February 2002 to February 2003. We
      performed non-parametric analyses to test the null hypothesis of no diference on
      waterbird density, and diversity among landscape units and seasons. The species
      composition was evaluated using ordination techniques. Waterbird density was
      higher in winter and autumn in the three lagoons of the study area, particularly
      in the insular coast, sandy beach and dunes; it was higher in the few segments of
      antropic sustrate. Diversity was significantly higher in mangrove habitat along
      the peninsular coast, and in mangrove-dunes association on the insular coast.
      Although modification of coastal natural habitat and boat transit disturbance had
      no influence on waterbird density or diversity, the highest richness of
      waterbirds occurred in well preserved areas. Species composition analysis showed
      differences between Santo Domingo Channel and Magdalena Bay. Pelagic and mangrove
      habitat had a species composition difference higher than those associations in
      other habitats. Such differences in species assemblages by habitat and landscape
      units suggest that communities are structured according to the range of available
      natural resources in structurally complex habitats, and that dominant piscivorous
      waterbird species were favored in this community.

PMID- 18624252
TI  - Waterbirds (other than Laridae) nesting in the middle section of Laguna Cuyutlan,
      Colima, Mexico.
AB  - Laguna de Cuyutlan, in the state of Colima, Mexico, is the only large coastal
      wetland in a span of roughly 1150 km. Despite this, the study of its birds has
      been largely neglected. Between 2003 and 2006 we assessed the waterbirds nesting
      in the middle portion of Laguna Cuyutlan, a large tropical coastal lagoon,
      through field visits. We documented the nesting of 15 species of non-Laridae
      waterbirds: Neotropic Cormorant (Phalacrocorax brasilianus), Tricolored Egret
      (Egretta tricolor), Snowy Egret (Egretta thula), Little Blue Heron (Egretta
      caerulea), Great Egret (Ardea alba), Cattle Egret (Bubulcus ibis), Black-crowned
      Night-heron (Nycticorax nycticorax), Yellow-crowned Night-heron (Nyctanassa
      violacea), Green Heron (Butorides virescens), Roseate Spoonbill (Platalea ajaja),
      White Ibis (Eudocimus albus), Black-bellied Whistling-duck (Dendrocygna
      autumnalis), Clapper Rail (Rallus longirostris), Snowy Plover (Charadrius
      alexandrinus), and Black-necked Stilt (Himantopus mexicanus). These add to six
      species of Laridae known to nest in that area: Laughing Gulls (Larus atricilla),
      Royal Terns (Thalasseus maximus), Gull-billed Terns (Gelochelidon nilotica),
      Forster's Terns (S. forsteri), Least Terns (Sternula antillarum), and Black
      Skimmer (Rynchops niger), and to at least 57 species using it during the non
      breeding season. With such bird assemblages, Laguna Cuyutlan is an important site
      for waterbirds, which should be given conservation status.

PMID- 18624253
TI  - [From the mechanical complexity in biology].
AB  - From the mechanical complexity in biology. Through history, each century has
      brought new discoveries and beliefs that have resulted in different perspectives
      to study life organisms. In this essay, 1 define three periods: in the first,
      organisms were studied in the context of their environment, in the second, on the
      basis of physical and chemical laws, and on the third, systemically. My analysis
      starts with primitive humans, continues to Aristoteles and Newton, Lamarck and
      Darwin, the DNA doble helix discovery, and the beginnings of reduccionism in
      science. I propose that life is paradigmatical, that it obeys physical and
      chemical laws but cannot be explained by them I review the systemic theory,
      autopoiesis, discipative structures and non- linear dynamics. 1 propose that the
      deterministic, lineal and quantitative paradigm of nature are not the only way to
      study nature and invite the reader to explore the complexity paradigm.

PMID- 18624254
TI  - Availability of oral swab sample for the detection of bovine viral diarrhea virus
      (BVDV) gene from the cattle persistently infected with BVDV.
AB  - Bovine nasal and oral discharges were used as samples for bovine viral diarrhea
      virus (BVDV) gene detection. Viral genes in serum (S), nasal discharge (N) and
      oral discharge (O) were quantified with real-time polymerase chain reaction using
      SYBR Green by the relative quantification method, and findings were compared
      among samples. Although the quantity of the BVDV gene in S was greater than those
      in N and O, all samples were available to identify persistently infected (PI)
      cattle with BVDV by reverse transcription polymerase chain reaction (RT-PCR). The
      swab samples were able to be stored for a few days at 4 degrees C with a little
      decrease of amplification signal in RT-PCR. Oral swab sampling was easier than
      nasal swab sampling, and was also less uncomfortable for the cattle than other
      sampling methods without pain or unnecessary retention. This sampling method can
      be performed without any special technique and equipment. Therefore, the oral
      swab sampling method is useful for screening to detect BVDV PI cattle by RT-PCR.

PMID- 18624255
TI  - Peer review confidentiality survives legal challenge.

PMID- 18624256
TI  - Occupation and chronic cough.

PMID- 18624257
TI  - Near miss maternal morbidity.
AB  - Audit of severe maternal morbidity is a potent tool in determining standards of
      maternity care. This study determines the incidence of severe acute maternal
      morbidity in our population, identifies the underlying organ dysfunction and
      associated obstetric risk factors, and compares them to published international
      reports. Over a 5 year period, 1999-2003, data were collected prospectively from
      patients with severe acute maternal morbidity. There were 36,802 women who
      delivered infants weighing more than 500 g over the 5 years with 53 cases of
      severe maternal morbidity. There were two indirect maternal deaths yielding an
      incidence of 1.4/1000 for severe maternal morbidity and 5.4/100,000 for maternal
      mortality. The severe maternal morbidity to mortality ratio was 26.5:1. Massive
      obstetric haemorrhage requiring acute blood transfusion of > or = 5 units of
      packed red cells occurred in 77% of cases. This study identifies the feasibility
      of audit of severe maternal morbidity using simple defined clinical criteria. The
      incidence and underlying aetiology of severe maternal morbidity in our unit is
      comparable to other developed countries. It is essential that data on severe
      maternal morbidity are reviewed and analysed continuously at local hospital and
      national level to assess, maintain and improve clinical standards.

PMID- 18624258
TI  - Attitudes of general practitioners to prehospital thrombolysis.
AB  - The aim of the study was to investigate attitudes of rural Irish General
      Practitioners (GPs) to prehospital thrombolysis. Postal questionnaires were sent
      to all General Medical Service (GMS) GPs in the former Western and North Western
      Health Board regions of Ireland, whose practices were 20km or greater from the
      nearest acute hospital with a coronary care unit. The response rate was 61%
      (117/191). 95% were convinced of the benefits of thrombolytic treatment in acute
      myocardial infarction. 92%/ believed that there were additional benefits of
      thrombolysing in the community at the earliest opportunity. 89% were not willing
      to use prehospital thrombolysis without further training. The study demonstrated
      that the majority of rural Irish GPs are convinced of the benefits of prehospital
      thrombolysis and are willing to administer it. The need for further training on
      prehospital thrombolysis is a key issue that must be addressed before rural Irish
      GPs are willing to provide more widespread prehospital thrombolysis.

PMID- 18624259
TI  - Cascade screening in BRCA1/2 mutation carriers.
AB  - Genetic counselling for families with BRCA1 & 2 has been available in Ireland
      since 1998. We describe the follow-on cascade from the initial 29 index cases
      that tested positive for either gene. 28 of the index cases were female and 1 was
      male. Their combined sibship and offspring totalled 125 and 129 respectively. Of
      the 125 siblings, 21/72 (29%) females and 10/53 (19%) males came forward for
      counselling and all were tested. Of the 129 at risk offspring, 56 (43%) [25
      females and 31 males] were over 18 years and therefore were eligible for testing.
      20/25 (80%) females and 6/31 (19%) males came for counselling and all bar one
      female was tested. In summary, 31/125 (25%) at risk siblings were tested and
      25/56 (45%) offspring were tested. Only one person, a daughter of an affected
      individual who attended clinic, declined testing. The remaining 197 (77%)
      individuals have not come forward for counselling. Our results suggest that a)
      there is a low-moderate testing rate in Ireland when compared to other European
      centres; and that b) daughters of BRCA1/2 carriers are more likely to come
      forward for testing than female siblings. Specific factors which appeared to
      influence attendance included poor dissemination of information among families
      about the test; and lower levels of communication among siblings than within the
      nuclear family.

PMID- 18624260
TI  - Neonatal resuscitation program guidelines 2006: ready, steady, can't go!
AB  - New evidence-based guidelines have been launched with recommendations that may
      impact how resuscitations, particularly of LBW infants, are enacted. AIM: to
      determine current resuscitation practices in Maternity units in Ireland and
      benchmarked these results to a recent study in the United States. METHODS: A 20
      question survey was developed and mailed to a lead neonatologist/paediatrician in
      each of 19 maternity units in Ireland in May 2006. RESULTS: There was 84%
      response rate to the surveys mailed which included 10 level II and 6 level III
      units. NRP qualification was considered obligatory for all paediatrics doctors in
      all units, with 14/16 units running at least one NRP course per year (range 1-9).
      Self inflating bags were more commonly used (44%), followed by T-piece
      resuscitators (31%) and flow inflating bags (25%). Pulse oximeters to alter the
      fraction of inspired oxygen were used by (25%) of units during the management of
      very low birth weigh infants, with a useful signal being achieved in one minute
      in most cases. Air/oxygen blenders were available for (44%) of units; however,
      all units use 100% O2 for initial resuscitation. CO2 detectors for ETT position
      were used in only 2 units (12%). A third of units (31%) used plastic wrap to
      prevent heat loss in VLBW infants. CPAP/PEEP were used by 44% of the surveyed
      units, generally with initiating pressure of 5 cm H2O. CONCLUSIONS: NRP is now an
      obligatory feature in all NICU's in Ireland compared to the 1990s when
      resuscitation training was disorganized and inconsistent. Variations in
      resuscitation practices still exist among different units. Many units may not be
      able to apply 2006 NRP guidelines especially for VLBW infants unless there is a
      significant investment in air/oxygen blenders, pulse oximeters, CO2 detectors and
      resuscitators that control peak pressures and CPAP/PEEP.

PMID- 18624261
TI  - Compliance in the measurement of CURB-65 in patients with community acquired
      pneumonia and potential implications for early discharge.
AB  - The CURB-65 community-acquired pneumonia (CAP) severity score is a convenient 5
      variable disease-specific tool validated to predict mortality and the decision to
      admit. This prospective study seeks to determine (a) the accuracy CAP diagnosis;
      (b) the degree to which the CURB-65 score was being documented; and (c) the
      degree to which CURB-65 was being utilised as an admission and early discharge
      tool in the A&E Department in the evaluation of patients presenting with CAP. Of
      45 patients referred with an admitting diagnosis of CAP, 28 were subsequently
      found to satisfy the criteria of CAP, an over diagnosis of 38%. Documentation of
      CURB-65 was 7%; recording of core variables was 81% i.e. 4 out of 5 variables and
      confusion was the variable least likely to be documented. On re-scoring, 50% of
      patients had a score of 0 or 1 and a further 28% had a score of 2. We conclude
      that CAP is significantly overdiagnosed; that the CURB-65 severity score is not
      being utilised and that between 50 and 78% of patients with CAP may be admitted
      unnecessarily. This study raises important issues in the current management of
      CAP in the Irish Healthcare system.

PMID- 18624262
TI  - A survey of the management of gout in primary care.
AB  - There is no information available regarding current practice and standards in
      management of gout in Irish general practice. This study aims to assess current
      practice in the context of the 2006 EULAR evidence based recommendations for
      diagnosis and management of gout. A 20 point questionnaire was circulated to all
      170 general practitioners in the North Dublin GP Partnership assessing frequency
      of diagnostic and therapeutic interventions undertaken. 91% of practitioners
      manage gout exclusively in primary care. 89% make a diagnosis on clinical grounds
      and 77% routinely measure serum urate. Diagnostic joint aspiration is rarely
      performed (3%). 86% routinely assess and manage risk factors for gout. 66%
      initiate urate-lowering therapy. Only 32% routinely monitor urate levels in
      patients receiving urate-lowering therapy. Thus, although management of gout in
      primary care in Ireland is generally in line with the EULAR recommendations some
      aspects of care remain suboptimal.

PMID- 18624263
TI  - Communication from an out-of-hours co-operative to general practice.

PMID- 18624264
TI  - A rare cause of acute abdomen--plasmodium falciparum leading to splenic
      infarction and haemorrhage.

PMID- 18624265
TI  - Cutaneous T-cell lymphoma presenting as a ten month history of unilateral facial
      swelling.
AB  - A 25-year-old fisherman presented with a ten-month history of unilateral facial
      swelling involving his lower lip and eyelids. The differential diagnosis for oro
      facial swelling is extensive including congenital, infective, inflammatory and
      neoplastic processes. Biopsies revealed a cutaneous T cell lymphoma.

PMID- 18624266
TI  - Reduction in non-attendance rates and assessment of patient opinions of an out-of
      hours outpatient clinic.

PMID- 18624267
TI  - Do new-generation antidepressants work?

PMID- 18624268
TI  - Transthoracic echocardiography is not useful in the routine investigation of
      ischaemic stroke or TIA.

PMID- 18624269
TI  - [Day by day in pediatric surgery].

PMID- 18624270
TI  - [Short bowel syndrome in the research setting: 15 years' experience].
AB  - The fight against infection and liver disease associated with parenteral
      nutrition (PN) are surely two of the most problematic aspects in the management
      of paediatric patients with short bowel syndrome (SBS). In the Research Unit of
      Donostia Hospital, we have spent the past 15 years investigating different ways
      of reducing these complications in an experimental model of short bowel in the
      Wistar rat (resection of 80% of the small bowel, with and without PN). All the
      experiments had a duration of 10 days and 323 animals reached the end of the
      study period. Nine groups were established in which some type of intervention was
      performed, and there were 8 control groups. The interventions were: 3 dietary
      (minimal enteral nutrition [MEN] with low or high dose probiotics); 5
      pharmacological (administration of growth hormone [GH], epidermal growth factor
      [EGF], insulin, cholecystokinin [CCK], and selective intestinal decontamination
      [SID]); and 1 surgical (resection of the ileocaecal valve). Infection due to
      bacterial translocation (BT) was detected by culture of mesenteric lymph nodes,
      portal blood and peripheral blood, and liver damage by the levels of
      proinflammatory cytokines (IL-1 and TNF-alpha). In summary, our results are:
      Probiotics, MEN and SID reduce BT. Liver damage was milder in the groups with
      MEN, SID and CCK. The groups receiving GH, EGF or insulin presented a higher
      incidence of BT. BT was lower after resection of the ileocaecal valve. In
      conclusion, the probiotics, MEN and CCK could be useful in the management of
      children with SBS. These data confirm the utility of this experimental model of
      short bowel for the investigation of different aspects of SBS.

PMID- 18624271
TI  - [Prognostic value of the ultrasound and diuretic renogram in the evolution of
      ureteropelvic junction obstruction].
AB  - INTRODUCTION: The congenital obstruction of the pieloureteral junction (UPJ) is
      the most frequent cause of hydronephrosis in children. Sometimes, establishing
      the convenience of a surgical procedure is difficult, mainly if we consider the
      literature published on the spontaneous resolution of the slight, moderate and
      even severe hydronephrosis in newborns. OBJECTIVE: To determine the prognostic
      value of ultrasound in the evolution of the unilateral hydronephrosis, by
      assesing the size of the contralateral kidney. To verify if the "supranormal"
      renal function (SRF) is real or an artefact. PATIENTS AND METHODS: We have
      performed a descriptive observational study over a 10 years period (1995-2005).
      The study included all patients with the only diagnosis of obstructive unilateral
      hydronephrosis that underwent pieloplasty, and were controlled for 1 year period
      after the surgical treatment. RESULTS: Of the 66 patients in the study, 42 were
      boys (63.6%) and 24 girls (36.4%). After the first diuretic renogram (DR), in 57
      of the patients (86.4%) the clearance half-time (T1/2) was over 20 minutes, in 6
      cases (9.1%) it was 10-20 minutes and only in 3 cases it was shorter than 10
      minutes. A similar differential renal function (FRD) was observed in the moderate
      and severe hydronephrosis. Supranormal function (FRD > 52%) was detected on DR in
      11 patients, predominating in left hidronefrosis, and in more than 50% of the
      cases this value it did not agree with the renal function measured by dimercapto
      succinic acid (DMSA), Pearson's correlation coefficient: 0.19. These kidneys
      experienced a greater reduction of the postoperative renal function. CONCLUSIONS:
      In the unilateral obstructive hydronephrosis, the healthy contralateral kidney
      experiences hypertrophy detectable by ultrasound, but these ecographic diameters
      are within the band of individual confidence of the healthy children of
      reference. The supranormal function exists, but in most cases it is an artefact.

PMID- 18624272
TI  - [Strategy for high cavoatrial tumor thrombus in children with nephroblastoma].
AB  - INTRODUCTION: Wilms tumor surgery with intracaval-atrial extension is a
      challenge. Modern imaging techniques, precise preoperative thrombus location, and
      multidisciplinary surgical approach is mandatory. We aim to evaluate the outcome
      of our patients. PATIENTS AND METHODS: Between 1992 and 2005, 52 patients with
      nephroblastomas underwent surgery in our institution. Nine of them had renal
      caval (RC) or cavo-atrial(CA) thrombus extension. Four patients presenting short
      RC intravascular extension were excluded. RESULTS: All cases were treated with
      pre-postoperative chemotherapy SIOP protocols. The level of the extension was
      retrohepatic in 2 cases, atrial in 3 patients and it even reached the ventricle
      in 2 of them. A multidisciplinary team was necessary to plan surgery and in all
      patients thrombus and tumor could be removed under cardiopulmonary by-pass in 3
      cases (CPBP). One pulmonary tamponade due to thrombus migration (CAV) occurred
      and was solved by CPBP. Three cases were stage III, one stage IV and 1 stage II.
      Conclusions. Tumor size can be significantly reduced by preoperative
      chemotherapy. In case of CA extension, CPBP and right liver displacement to gain
      access to retro-hepatic cava are mandatory in order to reduce surgical
      complications.

PMID- 18624273
TI  - [Surgical management and recurrence of congenital preauricular fistula].
AB  - In this paper we describe the surgical management and postoperative recurrence of
      preauricular fistula (PAF) since the surgical treatment is characterized by high
      recurrence rates. All clinical, operative and postoperative data were collected
      from a retrospective review of patients's charts who underwent primary surgical
      management between January 2001 and December 2006 at five Hospitals in
      Guadalajara, Jalisco. Thirty-eight patients (15 male, 23 female) with PAF
      underwent 44 surgical procedures. Recurrent acute infection and discharge were
      the most common symptoms. The surgical management included 25 standard techniques
      (sinectomy) and 19 supra-auricular approaches. The overall rate of recurrence was
      59%, it differed widely between surgical techniques employed. The 52.2%
      recurrence rate of standard technique was significantly higher than the 6.8%
      recurrence rate of the supra-auricular approach (p = 0.01). Also, the patients in
      whom a portion of the cartilage of the helix was not excised from the base of the
      tract, 84.6% recurred vs. 15.3% when cartilage was excised (p = 0.01). Our
      experience has shown that independently of clinical presentation of PAF, the
      standard technique and not to remove a portion of the cartilage at the base of
      the helix contributed to recurrence. We advise the supra-auricular approach
      particularly when there are abscess prior to surgery.

PMID- 18624274
TI  - [Diode laser application for the treatment of pediatric airway pathologies].
AB  - Laser application for the treatment of pediatric airway pathologies represents a
      very attractive option because of the limited inflammatory reaction after
      photocoagulation. One novel laser used for such pathologies is the diode laser.
      AIM: The purpose of this report is to present our preliminary experience in the
      use of diode laser in the treatment of pediatric airway lesions. METHODS: A
      retrospective review of 22 patients (11 males and 11 females) who underwent laser
      procedures from 1999 to 2006 was performed. Nineteen patients were treated at our
      center while 3 were referred after a laser application from other institution. In
      all procedures flexible bronchoscopy was used. The mean age was 1.25 years (range
      1 month-4.8 years). Lasers were applied for various lesions: laryngomalacia and
      arytenoid lesions (n = 5), angiomas (n = 3), lymphangiomas (n = 3), sacular cyst
      and other mucous lesions (n = 3), granulomas, scarring lesions (n = 4) and
      paralysis of vocal cord in adduction (n = 1). RESULTS: None of the patient
      developed complications related to the endoscopic laser application. The mean
      number of laser therapy attempts were 1.4 per patient (range 1-3). The patients
      remained intubated for a mean of 2.8 days (range 4 hours-13 days) after the
      procedure. The duration of PICU stay after laser therapy was a mean of 4.6 days
      (range 1-8 days). The best outcomes were seen in sacular cysts (excelent in 3
      patients). Also, all 3 patients with granulomas showed a good response to
      treatment. Multiple laser sessions (1-3; mean 1.4) were required to sucessfully
      manage the artynenoid lesions. However, the children with vascular lesions
      demonstrated differents outcomes. Of the 3 patients with subglottic angioma, 2
      underwent a subsequent surgical procedure due to the development of subglottic
      stenosis; and one requiered further systemic steroid therapy. Of the children
      with lymphangioma, one needed 3 laser sessions and two required surgi- cal
      resections. Despite laser treatment, 3 of the 4 patients with scarring lesions
      required surgery. CONCLUSIONS: The endoscopic application of diode laser for the
      management of pediatric airways lesions provides good outcomes in selected
      patients. Sacular lesions, granulomas and arytenoid lesions are, in our
      experience, excellents indications. In other anomalies laser is a good adjuvant.
      The application of laser should be tailored according to the pathology.

PMID- 18624275
TI  - [Pain and anxiety in pediatric surgery].
AB  - INTRODUCTION: Postsurgery pain is a common complaint in children and significant
      postoperative pain may last for weeks. Severe perisurgery pain may aggravate long
      lasting negative effects. In order to prevent harmful effects, children should be
      provided with effective-secure analgesia. The aim of this work was to determine
      current practice of postsurgery pain management in children. MATERIAL AND
      METHODS: An observational prospective study in pediatric patients undergoing
      surgery in our hospital was performed. Children's (< 14 years old) having
      elective major surgery and outpatient surgery were collected prospectively.
      Clinical stage, surgery and anaesthesia procedures, postsurgery analgesia and
      perioperative complications were recorded. Pain control was measured by an
      analogic visual scale (AVS) before surgery, in post-anaesthesia recovery unit
      (PARU), in one-day unit (ODU) and 24 h after surgery (24hU). STATISTICAL
      ANALYSIS: mean values +/- sem or SD, frequency and percentage of incidence of N
      cases, t-test, ANOVA of one and several ways, chi-square, correlations of two
      variables, linear and logistic regressions depending of variables' types.
      RESULTS: 77 patients with mean age of 5 years old and mean weight of 22 kg were
      studied. The most frequently employed anesthetic technique was the general one.
      Forty per cent of the patients were pre-medicated with midazolam. Little pain
      before surgery is observed and after surgery it is moderate. Anxiety is higher
      after surgery and immediately after it in the recovery room or the Post
      Anesthesia Care Unit (PACU), subsequently it diminishes, especially patients with
      same-day admission surgery. Positive correlations between pain and anxiety
      intensities were found in each determination done. CONCLUSIONS: Is observed that
      pain and anxiety round surgery in children had insufficient treatment, reason why
      we think we should make treatment protocols, adapted at this population, its
      necessities and the different types of procedures they can be subjected.

PMID- 18624276
TI  - [Biofeedback and electrostimulation in the treatment of non monosymptomatic
      enuresis].
AB  - AIM: To show our experience with biofeedback and electrostimulation techniques in
      the treatment of non monosymptomatic enuresis. METHODS: We reviewed biofeedback
      and electrostimulation techniques in the treatment of complicated enuresis
      carried out in our institution between 1995 and 2000. We report 99 patients (65
      girls and 34 boys) with ages ranging from 5 to 14 years old. A complete urodinamy
      study divided the patients into 5 groups: detrusor-sphincter dysfunction (DSD)
      (47 patients), detrusor overactivity (DO) (25 patients), urge syndrome (US) (15
      patients), sphincter hypertony (SH) (10 patients) and "retentionist" bladder (RB)
      (2 patients). Success was defined as less than three wet nights in a month.
      Biofeedback and electrostimulation program was designed in 10 sessions per week
      (20 minutes each session) with SIGMAX-Biomedical software. Tibial
      electrostimulation with SANS-UroSurge equipment was indicated when biofeedback
      and electrostimulation techniques failed (12 sessions per week, 30 minutes each
      session). RESULTS. The success rate has been 78.9% in DSD group, 80% in DO group,
      85% in US group, 75% in SH group, 100% in RB group. CONCLUSIONS: Effectiveness of
      biofeedback and electrostimulation techniques in the treatment of non
      monosymptomatic enuresis has been reported and seems to be permanent in time.

PMID- 18624277
TI  - [Reoperations in gastroesophageal reflux disease].
AB  - PURPOSE: The purpose was to determinate the indications in which the failure of
      the surgical treatment of the gastroesophageal reflux disease (GERD) is more
      frequent and to analyze the results of the reinterventions. PATIENTS AND METHOD:
      We made a restrospective review of the patients who underwent reoperation at our
      Institution during 1992-2006. RESULTS: 19 of 252 Nissen underwent reoperation. In
      one case was the fourth fundoplication, in another was the third and the second
      in the rest of them. The reflux was confirmed by upper gastrointestinal contrast
      study, endoscopy, pH monitoring and, in some cases, manometry. 5 cases have
      surgical comorbidity (3 Esophageal Atresia (EA), 2 Congenital diaphragmatic
      hernia (CDH), 4 patients was neurologically impaired, 1 had caustic stenosis
      (CS), and 9 only symptoms of GERD. 8.7% of the patients with GERD, 5.8% of the
      neurologically impaired children, 10% of the EA, 20% of the CDH and 50% of the CS
      underwent redo Nissen. The mean time between first and second fundoplication was
      1.6 years (range = 1 m-5.5 y). It was 11.2 in neurologically impaired patients, 5
      m in CS, 11.5 m in CDH, 2.4 y in EA and 2.8 y in the rest. In patients with
      respiratory disease, the mean was 1.1 y and 1.9 y in the rest. The mechanism of
      failure was herniation of the fundoplication through the hiatus in 8 cases, wrap
      incompetence in 4 and wrap dehiscence in 2. In 5 patients it couldn't be
      determined. There were 2 postoperative complications. The mean follow-up was 5.3
      years (range = 6-151.5 m). There was no cases of mortality. 17 of the 19 patients
      (89.4%) are free of symptoms and don't need more treatments. The child with CS
      continuous periodic esophageal dilatations and 1 of the patients with EA has
      dysphagia to solid foods.

PMID- 18624278
TI  - [Must we change the surgical treatment of gallstones?].
AB  - The incidence of gallstones in childhood is 0.15%-0.22%. Frequency has increased
      in recent years due to a real increase or to a better diagnosis by ultrasound.
      The aim of our study is determinate the best treatment for every patient.
      MATERIALS AND METHODS: A retrospective study of 71 children with cholelithiasis
      admitted to our hospital in the last 20 years. RESULTS: The male to female ratio
      was 43:28. Seventeen patients present predisposing factors that might be related
      to the formation of gallstones. This disease was a casual event in half the
      cases. In 24 patients the diagnosis was made during a study for inspecific
      abdominal pain and 14 children showed typical symptoms. Only one patient suffer
      from acute cholecystitis. In 21 cases we find a single stone and in the other
      cases there were a lot of stones. The gallstones disappeared spontaneously in two
      patients. Nine children received treatment with ursodeoxycholic acid, but this
      treatment was ineffective in 8 of them. 27 patients were operated: Six
      laparoscopic cholecystectomy, 9 open cholecystectomy, 9 cholecystolithotomy and 3
      cholecystectomy with splenectomy. CONCLUSIONS: We recommend periodic checks with
      ultrasound and conservative management is suggested in asymptomatic children.
      Operative intervention is recommended for symptomatic patients. The surgical
      treatment of choice in our centre for patients with solitary gallstones and
      without inflammatory changes in the gallbladder is cholecystolithotomy. We didn't
      find reappearence of gallbladder after cholecystolithotomy. Laparoscopic
      cholecystectomy is the best treatment for children with non working gallbladder,
      "porcelain gallbladder" and in patients with haematologic disease and gallstones.

PMID- 18624279
TI  - [Is immediate prophylactic thyroidectomy indispensable in familiar medullary
      thyroid carcinoma?].
AB  - PURPOSE: To emphasize the importance of genetic studies in family members and
      early prophylactic thyroidectomy in oncogene mutation carriers in the management
      of familiar medullary thyroid carcinoma. METHODS: A retrospective review of
      families with familiar medullary thyroid carcinoma treated at our center in the
      last 7 years was performed. We identified a total of 7 families who has isolated
      prevalences with thyroid malignancies. Forty members of the 7 families were
      screened for gene RET mutations. Prophylactic total thyroidectomy was performed
      in every RET mutation gene carriers. RESULTS: In all families the index case were
      patients with medullary thyroid carcinoma presenting at a mean age of 37.25 years
      (range 23-42). The RET oncogen mutation was in codon 634 in exon 11 (multiple
      endocrine neoplasia type 2A) in all these patients. Fourteen gene carriers were
      identified with a mean age of 20 years (range 7-37), eleven of whom had medullary
      thyroid carcinoma at the time of surgery. Five of the gene carriers were
      children, with a mean age of 11 years (range 7-16), four of whom had
      microcarcinoma and one had metastatic carcinoma at the time of surgery. After
      surgery no hypoparathyroidism or recurrent nerve paralysis were documented. No
      pediatric patient has presented with phaeochromocytoma or hypoparathyroidism to
      date Four of the five children have normal calcitonin levels (< 2 pg/ml) and they
      are free of disease. The one who presented metastatic carcinoma has recurrent
      disease and is awaiting surgical treatment. CONCLUSIONS: Genetic studies of
      family members related to patients with familiar medullary thyroid carcinoma and
      RET mutations is indispensable. The RET mutation in codon 634 exon 11 was found
      to be the most frequent association. Prophylactic thyroidectomy is the only
      curative treatment and has minimal complications when performed by expert
      surgeons. Early thyroidectomy is recommended since distant metastatic spread can
      occur at early age.

PMID- 18624280
TI  - [A satisfaction survey of the evolution of 238 otoplasty].
AB  - PURPOSE: The prominent ear is a frequent problem that can be a source of
      important psychosocial troubles. The aim of this paper has been to evaluate the
      psychosocial repercussion, cosmetic result and degree of satisfaction in patients
      treated at our Institution for prominent ears in the last 4 years. MATERIAL AND
      METHODS: A questionnaire has been sent to 127 patients. All of them underwent
      Mustarde's otoplasty. RESULTS: 238 otoplasty were performed in 127 patients (87%
      bilateral procedures). The mean age was 8.15 +/- 3.25 years (range: 1-15 years),
      with a follow-up of 27.15 +/- 13.62 months (range: 4-52 months). Sixty-two % of
      the patients underwent otoplasty without having self-image affected while 38% of
      the group were patients older enough to see surgery to correct a long-standing
      defect. Patients did not require a period of postoperative psychosocial
      adjustment to their new appearance. Two patients described their results of
      surgery as little improvement. Three undergo partial recurrence and 5 suffered
      from total recurrence. All of the patients resume their lives with an improved
      level of self confidence. Conclusions. Otoplasty is a safe procedure for
      prominent ears to be considered in children with psycosocial, emotional or
      behavioural effects.

PMID- 18624281
TI  - [Thoracoscopic lobectomy in patients with congenital cystic adenomatoid
      malformation].
AB  - BACKGROUND: The management of asymptomatic patients with congenital cystic
      adenomatoid malformation (CCAM) is controversial. This report evaluates the video
      assisted thoracoscopic (VAT) lobectomy in children with this malformation, and
      the different intraoperative complications and their resolution are discussed.
      METHODS: Six patients with CCAM underwent video-assisted thoracoscopic lobectomy.
      All the patients were under one year and all of them were asymptomatic at the
      diagnosis. The procedures were performed with single lung ventilation and the
      chest was insufflated with a low flow and pressure to complete collapse of the
      lung. We used 3 or 4 thoracoscopic ports depending on the difficulty of the
      dissection. A bipolar sealing device was the preferred mode of vessel ligation
      and bronchi were closed with interrupted sutures. The following features have
      been taken into account: age at diagnosis, localization, surgical technique,
      complications, hospital stay, results, and time of follow-up. RESULTS: Four
      lesions were on the right lower lobe (66.7%) and two (33.3%) in the middle lobe.
      All the procedures were completed thoracoscopically. Chest tubes were left in all
      cases. Two patients (33.3%) showed postoperative hemothorax but it didn't need
      blood transfusion. Mean hospital stay was 6 days. At the moment all the patients
      are asymptomatic with and the mean time of follow-up has been 2 years and 8
      months. CONCLUSIONS: VAT lobectomy avoids the long-term morbidity associated to
      an open thoracotomy and therefore it is a safe and efficacious technique in
      asymptomatic children with CCAM. Moreover, a greater number of cases are
      necessary to validate and to improve the technique.

PMID- 18624282
TI  - [Modified "trap-door" thoracotomy for pediatric patients].
AB  - INTRODUCTION: Surgical approach of the cervicothoracic junction has been
      traditionally done by cervicotomy and/or thoracotomy. Nevertheless, this access
      does not allow a suitable control of vasculonervous structures. Due to this we
      present our experience with a variation of the "Trap-door" thoracotomy which
      gives the best access to this area applied to pediatric patients METHODS: We
      present 4 patients of 2.8 +/- 1.9 years of age treated in our hospital by a
      cervicothoracotomy transmanubrial approach without clavicular luxation. One
      patient presented a stage IV cervicothoracic neuroblastoma, 1 patient had a
      cervicothoracic lymphangioma, one a severe cervicothoracic scoliosis and one a
      total cricoid atresia associated to an oesophageal atresia type IIIc (Vogt). This
      surgical approach allowed a perfect control of brachiocefalic and nervous
      structures as well as a correct visualization of all the cervicothoracic
      intervertebral foramina. Postoperative pain was controlled by epidural catheters,
      oral analgesic treatment was introduced in the fifth postoperative day. RESULTS:
      Complete resection and surgical treatment was possible in all patients, not being
      necessary the section of any vascular or nervous structure. There were no
      intraoperatory or postoperative complications. One patient presented a temporary
      Homer's syndrome. No tumoral recurrence has been noted after a mean follow-up of
      2.3 +/- 3.1 years. CONCLUSION. The modified "Trap-door" approach allows a good
      control of the brachiocephalic structures and a complete visualization of the
      upper thorax and posterior mediastinum. Due to its low morbidity this access may
      be very useful since it allows an important vascular control and an excellent
      surgical field. Our modification of the "Trap-door" approach avoids clavicular
      luxation and has the advantage of no sequelaes in the functionality of the
      escapulo-humeral articulation.

PMID- 18624283
TI  - [Videothorascocopic: approach in thoracic inlet of neurogenic mediastinal tumor
      in pediatric age].
AB  - We present a 4 year-old patient with precedent of pneumonia and showing an
      increase of X-ray density in the superior mediastinal. After a year of follow-up
      and the presence of irritating cough, it is decided to perform studies of image
      (CT), being diagnosed of a mass in the region of the thoracic inlet which affects
      up to D4. Video-assisted thoracic surgery is decided and the mass is entirely
      removed, being the result of the pathological study to ganglioneuroma. Eight
      months later from, the patient is asymptomatic and without relapse according to
      the image methods which were carried out.

PMID- 18624284
TI  - Maintenance of undifferentiated mouse embryonic stem cells in suspension by the
      serum- and feeder-free defined culture condition.
AB  - The proven pluripotency of ES cells is expected to allow their therapeutic use
      for regenerative medicine. We present here a novel suspension culture method that
      facilitates the proliferation of pluripotent ES cells without feeder cells. The
      culture medium contains polyvinyl alcohol (PVA), free of either animal-derived or
      synthetic serum, and contains very low amounts of peptidic or proteinaceous
      materials, which are favorable for therapeutic use. ES cells showed sustained
      proliferation in the suspension culture, and their undifferentiated state and
      pluripotency were experimentally verified. DNA microarray analyses showed a close
      relationship between the elevated expression of genes related to cell adhesions.
      We suggest that this suspension culture condition provides a better alternative
      to the conventional attached cell culture condition, especially for possible
      therapeutic use, by limiting the exposure of ES cells to feeder cells and animal
      products.

PMID- 18624286
TI  - Photodissociation of dibromobenzenes at 266 nm by the velocity imaging technique.
AB  - A velocity imaging technique combined with (2+1) resonance-enhanced multiphoton
      ionization (REMPI) is used to detect the primary Br((2)P(3/2)) fragment in the
      photodissociation of o-, m-, and p-dibromobenzene at 266 nm. The obtained
      translational energy distributions suggest that the Br fragments are produced via
      two dissociation channels. For o- and m-dibromobenzene, the slow channel that
      yields an anisotropy parameter close to zero is proposed to stem from excitation
      of the lowest excited singlet (pi,pi*) state followed by predissociation along a
      repulsive triplet (n,sigma*) state localized on the C-Br bond. The fast channel
      that gives rise to an anisotropy parameter of 0.53-0.73 is attributed to a bound
      triplet state with smaller dissociation barrier. For p-dibromobenzene, the
      dissociation rates are reversed, because the barrier for the bound triplet state
      becomes higher than the singlet-triplet crossing energy. The fractions of
      translational energy release are determined to be 6-8 and 29-40 % for the slow
      and fast channels, respectively; the quantum yields are 0.2 and 0.8, and are
      insensitive to the position of the substituent. The Br fragmentation from
      bromobenzene and bromofluorobenzenes at the same photolyzing wavelength is also
      compared to understand the effect of the number of halogen atoms on the phenyl
      ring.

PMID- 18624287
TI  - Complex interfaces and their role in protein-stabilized soft materials.

PMID- 18624285
TI  - Human primary corneal fibroblasts synthesize and deposit proteoglycans in long
      term 3-D cultures.
AB  - Our goal was to develop a 3-D multi-cellular construct using primary human
      corneal fibroblasts cultured on a disorganized collagen substrate in a scaffold
      free environment and to use it to determine the regulation of proteoglycans over
      an extended period of time (11 weeks). Electron micrographs revealed multi
      layered constructs with cells present in between alternating parallel and
      perpendicular arrays of fibrils. Type I collagen increased 2-4-fold. Stromal
      proteoglycans including lumican, syndecan4, decorin, biglycan, mimecan, and
      perlecan were expressed. The presence of glycosaminoglycan chains was
      demonstrated for a subset of the core proteins (lumican, biglycan, and decorin)
      using lyase digestion. Cuprolinic blue-stained cultures showed that sulfated
      proteoglycans were present throughout the construct and most prominent in its mid
      region. The size of the Cuprolinic-positive filaments resembled those previously
      reported in a human corneal stroma. Under the current culture conditions, the
      cells mimic a development or nonfibrotic repair phenotype.

PMID- 18624288
TI  - Screening electronic communication through ortho-, meta- and para-substituted
      linkers separating subphthalocyanines and C60.
AB  - We have prepared two complementary series of SubPc-C(60)
      (SubPc=subphthalocyanine) electron/energy donor-acceptor systems, in which the
      two constituents are linked through ortho-, meta-, or para-substituted phenoxy
      spacers. In one of the series (1 a) the SubPc units bear iodine atoms, while in
      the other series (1 b) diphenylamino groups are linked to the SubPc macrocycles.
      The iodine atoms and diphenylamino groups both influence the resulting oxidation
      potentials of the electron-donating SubPc. They also modulate the outcome of
      excited state interactions, namely, energy and/or charge transfer. In addition,
      we have studied the impact that the substitution pattern in the phenoxy spacer
      exerts onto intramolecular processes in the ground and excited states. Although
      some of these processes are governed by the spatial separation between both
      components, the different electronic coupling through ortho-, meta-, or para-
      connections also plays decisive roles in some cases.

PMID- 18624289
TI  - Na8[Cr4B12P8O44(OH)4][P2O7].nH2O: a 3D borophosphate framework with spherical
      cages.
AB  - A chromium borophosphate-phosphate
      (Na(8)[Cr(4)B(12)P(8)O(44)(OH)(4)][P(2)O(7)]nH(2)O, 1), which has an unusual 3D
      framework structure, was synthesized under hydrothermal conditions. The framework
      consists of spherical cages composed of CrO(6), PO(4), BO(4), and BO(3)
      polyhedra. The cages are located at the vertices and the body center of the cubic
      cell and are interconnected through 12-membered-ring windows along the {111}
      direction. The actual framework structure is very complex, but the description
      can be simplified by using the 5-connected fundamental building cluster
      [CrP(5)B(3)O(24)](11-). In addition, 1 represents the first borate-rich
      borophosphate that contains a 3D borophosphate partial framework
      (3(over)infinity[B(3)P(2)O(11)(OH)]) in which the fundamental building unit is an
      oB dreier single ring (Delta4 square:square<Delta2 square> square). The cavities
      of the framework are filled with disengaged water molecules and Na(+)
      counterions. The former can be reversibly desorbed and reabsorbed and the latter
      can be exchanged by Li(+) ions, which results in significant shrinkages of the
      cell volume.

PMID- 18624290
TI  - Evidence that the KIR2DS5 gene codes for a surface receptor triggering natural
      killer cell function.
AB  - In this study, after immunization with NK cells from a KIR2DS5(+) donor and
      screening on cell transfectants expressing different members of the killer
      immunoglobulin-like receptor (KIR) family, we generated a mAb, DF200, reacting
      with several KIR2D receptors including KIR2DL1/L2/L3, KIR2DS1/S2 and KIR2DS5. By
      the analysis of peripheral blood NK cells and in vitro derived NK cell clones, we
      have demonstrated for the first time that KIR2DS5 is expressed at the cell
      surface in discrete subsets of NK cells and, after DF200 mAb-mediated engagement,
      can induce both cytotoxicity and cytokine release. Using co-transfection and co
      immunoprecipitation, we found that KIR2DS5 associates with the DAP12 signaling
      polypeptide. Finally, soluble KIR2DS5-Fc fusion protein does not bind to cell
      transfectants expressing different HLA-C alleles, suggesting that, if KIR2DS5
      does recognize HLA-C molecules, this may only occur in the presence of certain
      peptides.

PMID- 18624291
TI  - Steric effects in RNA interference: probing the influence of nucleobase size and
      shape.
AB  - Nonpolar nucleosides with varying size and shape have been used to study the
      hydrogen-bonding stabilization and steric effects on RNA interference. The uracil
      and adenine residues of siRNA guide strands have been replaced by nonpolar
      isosteres of uracil and adenine and by steric variants. RNAi experiments
      targeting Renilla luciferase mRNA have shown close correlation between siRNA
      thermal stability and gene suppression. Interestingly, siRNA modified at position
      7 on the guide strand does not follow this correlation, having substantial RNAi
      activity despite low thermal stability. Sequence-selectivity studies were carried
      out at this position with mutated target mRNAs and nucleobase analogues with
      varied size (2,4-difluoro- and 2,4-dichlorobenzene) and different shape (2,3
      dichlorobenzene, 4-methylbenzimidazole). The results point out the importance of
      nucleobase shape and steric effects in RNA interference.

PMID- 18624293
TI  - An improved mechanism-based cross-linker for multiplexed kinase detection and
      inhibition in a complex proteome.

PMID- 18624292
TI  - CXCL10/CXCR3-mediated responses promote immunity to respiratory syncytial virus
      infection by augmenting dendritic cell and CD8(+) T cell efficacy.
AB  - The induction of inflammatory cytokines during respiratory viral infections
      contributes to both disease pathogenesis and resolution. The present studies
      investigated the role of the chemokine CXCL10 and its specific receptor, CXCR3,
      in the host response to pulmonary respiratory syncytial virus (RSV) infection.
      Antibody-mediated neutralization of CXCL10 resulted in a significant increase in
      disease pathogenesis, including airway hyperresponsiveness (AHR), mucus gene
      expression, and impaired viral clearance. When the pulmonary cytokine levels were
      examined, only type I IFN and IL-12p70 were significantly reduced. These latter
      observations were reflected in reduced dendritic cell (DC) numbers and DC
      maturation in the lungs of RSV-infected mice treated with anti-CXCL10.
      Neutralization of the only known receptor for CXCL10, CXCR3, resulted in similar
      increases in pathogenic responses. When bone marrow-derived DC were incubated
      with CXCL10 and RSV, an up-regulation of type I IFN was observed. In addition, T
      lymphocytes were also examined and a significant decrease in the number of RSV M2
      peptide-specific CD8(+) T cells was identified. These findings highlight a
      previously unappreciated role for the CXCL10:CXCR3 signaling axis in RSV-infected
      animals by recruiting virus-specific T cells into the lung and promoting viral
      clearance.

PMID- 18624294
TI  - Cobalt-mediated radical polymerization of acrylonitrile: kinetics investigations
      and DFT calculations.
AB  - The successful controlled homopolymerization of acrylonitrile (AN) by cobalt
      mediated radical polymerization (CMRP) is reported for the first time. As a rule,
      initiation of the polymerization was carried out starting from a conventional azo
      initiator (V-70) in the presence of bis(acetylacetonato)cobalt(II)
      ([Co(acac)(2)]) but also by using organocobalt(III) adducts. Molar concentration
      ratios of the reactants, the temperature, and the solvent were tuned, and the
      effect of these parameters on the course of the polymerization is discussed in
      detail. The best level of control was observed when the AN polymerization was
      initiated by an organocobalt(III) adduct at 0 degrees C in dimethyl sulfoxide.
      Under these conditions, poly(acrylonitrile) with a predictable molar mass and
      molar mass distribution as low as 1.1 was prepared. A combination of kinetic
      data, X-ray analyses, and DFT calculations were used to rationalize the results
      and to draw conclusions on the key role played by the solvent molecules in the
      process. These important mechanistic insights also permit an explanation of the
      unexpected "solvent effect" that allows the preparation of well-defined
      poly(vinyl acetate)-b-poly(acrylonitrile) by CMRP.

PMID- 18624295
TI  - Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent
      natural killer T cells.
AB  - Invariant natural killer T (iNKT) cells are a special subset of alphabeta T cells
      with invariant TCR, which recognize alpha-galactosylceramide (alpha-GalCer)
      presented by CD1d. In addition to signals through the invariant TCR upon
      stimulation with alpha-GalCer, costimulatory signals, such as signals through
      CD28 and OX40, are indispensable for full activation of iNKT cells. In this
      study, we investigated the functions of a well-known costimulatory molecule,
      glucocorticoid-induced TNF receptor (GITR), on Ag-induced iNKT cell activation.
      Unexpectedly, engagement of GITR by agonistic mAb DTA-1 suppressed proliferation
      and cytokine production of iNKT cells upon alpha-GalCer stimulation. In addition,
      GITR signals in iNKT cells during only the Ag-priming phase was sufficient to
      inhibit the iNKT cell activation. Consistent with these results, the GITR
      deficient iNKT cells showed enhanced proliferation and increased cytokine
      production upon alpha-GalCer stimulation both in vitro and in vivo. Furthermore,
      the in vivo administration of alpha-GalCer suppressed tumor metastasis more
      efficiently in GITR-deficient mice than in wild-type mice. Collectively, GITR
      plays a co-inhibitory role in Ag-induced iNKT cell activation.

PMID- 18624296
TI  - Modular chiral bidentate phosphonites: design, synthesis, and application in
      catalytic asymmetric hydroformylation reactions.
AB  - A new class of C2-symmetric chiral bidentate phosphonite ligands has been
      synthesized in moderate to good yields from readily available starting materials.
      Application of these air-stable chiral phosphonites in the Rh I-catalyzed
      asymmetric hydroformylation of styrene derivatives, vinyl acetate, and allyl
      cyanide afforded the corresponding chiral aldehydes with high regio- and
      enantioselectivities under mild reaction conditions. The modular nature of the
      ligands allows fine-tuning of the selectivities through judicious modifications
      of the substituents on the ligand backbone. X-ray structural analysis of the
      catalyst precursor suggested that the steric hindrance caused by the protruding
      remote substituents of the ligands into the vicinity of the metal center might be
      an important factor for the enantio-control of the reaction, whereas the sense of
      asymmetric induction can be rationalized on the basis of a trigonal-bipyramidal
      transition state diagram.

PMID- 18624297
TI  - Inhibition of apoptosis in Bacteroides fragilis enterotoxin-stimulated intestinal
      epithelial cells through the induction of c-IAP-2.
AB  - Enterotoxigenic Bacteroides fragilis produces an approximately 20-kDa heat-labile
      enterotoxin (BFT) that plays an essential role in generating mucosal
      inflammation. Although it is well known that proinflammatory signals are
      expressed in BFT-stimulated intestinal epithelial cells, cell death processes
      have not been elucidated. BFT induced apoptosis in HT-29 cells, but the apoptosis
      was first apparent 36 h after stimulation. During the early period of BFT
      stimulation, expression of cellular inhibitor of apoptosis protein-2 (c-IAP2)
      increased, and inhibition of c-IAP2 augmented the apoptotic cell death.
      Inhibition of BFT-induced COX-2 expression decreased prostaglandin E(2) (PGE(2))
      production, which led not only to a decrease of c-IAP2 activity but also to an
      enhancement of DNA fragmentation in the early period of BFT stimulation.
      Furthermore, apoptosis inhibition through PGE(2) and c-IAP2 was mainly regulated
      by a p38 mitogen-activated protein kinase (MAPK). These results suggest that the
      inhibition of apoptosis may be mediated by a sequential pathway, including MAPK,
      COX-2, PGE(2) and c-IAP2, in the early period of stimulation. The delay in the
      onset of epithelial cell apoptosis after enterotoxigenic B. fragilis infection
      may be important to the host since it can provides sufficient time for epithelial
      cells to generate signals for the activation of mucosal inflammation and it may
      increase the chances of bacterial colonization.

PMID- 18624298
TI  - Isomeric effect on microscale self-assembly: interplay between molecular property
      and solvent polarity in the formation of 1 D n-type microbelts.

PMID- 18624300
TI  - HP-Ca2Si5N8--a new high-pressure nitridosilicate: synthesis, structure,
      luminescence, and DFT calculations.
AB  - HP-Ca2Si5N8 was obtained by means of high-pressure high-temperature synthesis
      utilizing the multianvil technique (6 to 12 GPa, 900 to 1200 degrees C) starting
      from the ambient-pressure phase Ca2Si5N8. HP-Ca2Si5N8 crystallizes in the
      orthorhombic crystal system (Pbca (no. 61), a=1058.4(2), b=965.2(2), c=1366.3(3)
      pm, V=1395.7(7)x10(6) pm3, Z=8, R1=0.1191). The HP-Ca2Si5N8 structure is built up
      by a three-dimensional, highly condensed nitridosilicate framework with N[2] as
      well as N[3] bridging. Corrugated layers of corner-sharing SiN4 tetrahedra are
      interconnected by further SiN4 units. The Ca2+ ions are situated between these
      layers with coordination numbers 6+1 and 7+1, respectively. HP-Ca2Si5N8 as well
      as hypothetical orthorhombic o-Ca2Si5N8 (isostructural to the ambient-pressure
      modifications of Sr2Si5N8 and Ba2Si5N8) were studied as high-pressure phases of
      Ca2Si5N8 up to 100 GPa by using density functional calculations. The transition
      pressure into HP-Ca2Si5N8 was calculated to 1.7 GPa, whereas o-Ca2Si5N8 will not
      be adopted as a high-pressure phase. Two different decomposition pathways of
      Ca2Si5N8 (into Ca3N2 and Si3N4 or into CaSiN2 and Si3N4) and their pressure
      dependence were examined. It was found that a pressure-induced decomposition of
      Ca2Si5N8 into CaSiN2 and Si3N4 is preferred and that Ca2Si5N8 is no longer
      thermodynamically stable under pressures exceeding 15 GPa. Luminescence
      investigations (excitation at 365 nm) of HP-Ca2Si5N8:Eu2+ reveal a broadband
      emission peaking at 627 nm (FWHM=97 nm), similar to the ambient-pressure phase
      Ca2Si5N8:Eu2+.

PMID- 18624299
TI  - DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T
      lymphocytes from a tolerized repertoire.
AB  - The majority of known human tumor-associated antigens derive from non-mutated
      self proteins. T cell tolerance, essential to prevent autoimmunity, must
      therefore be cautiously circumvented to generate cytotoxic T cell responses
      against these targets. Our strategy uses DNA fusion vaccines to activate high
      levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate
      tolerance-breaking CD4(+) T cell help. Candidate MHC class I-binding tumor
      peptide sequences are fused to the C terminus for optimal processing and
      presentation. To model performance against a leukemia-associated antigen in a
      tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL
      epitope derived from Friend murine leukemia virus gag protein (FMuLV(gag)) and
      vaccinated tolerant FMuLV(gag)-transgenic (gag-Tg) mice. Vaccination with the
      construct induced epitope-specific IFN-gamma-producing CD8(+) T cells in normal
      and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag
      Tg mice, and no autoimmune injury resulted. However, these CD8(+) T cells did
      exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific
      CTL killed FBL-3 leukemia cells expressing endogenous FMuLV(gag) antigen and
      protected against leukemia challenge in vivo. These results demonstrate a simple
      strategy to engage anti-microbial T cell help to activate epitope-specific
      polyclonal CD8(+) T cell responses from a residual tolerized repertoire.

PMID- 18624301
TI  - A subset of IL-10-producing gammadelta T cells protect the liver from Listeria
      elicited, CD8(+) T cell-mediated injury.
AB  - Although gammadelta T cells play a role in protecting tissues from pathogen
      elicited damage to bacterial, viral and parasitic pathogens, the mechanisms
      involved in the damage and in the protection have not been clearly elucidated.
      This has been addressed using a murine model of listeriosis, which in mice
      lacking gammadelta T cells (TCRdelta(-/-)) is characterised by severe and
      extensive immune-mediated hepatic necrosis. We show that these hepatic lesions
      are caused by Listeria-elicited CD8(+) T cells secreting high levels of TNF-alpha
      that accumulate in the liver of Listeria-infected TCRdelta(-/-) mice. Using
      isolated populations of gammadelta T cells from wild-type and cytokine-deficient
      strains of mice to reconstitute TCRdelta(-/-) mice, the TCR variable gene 4
      (Vgamma4)(+) subset of gammadelta T cells was shown to protect against liver
      injury. Hepatoprotection was dependent upon their ability to produce IL-10 after
      TCR-mediated interactions with Listeria-elicited macrophages and CD8(+) T cells.
      IL-10-producing Vgamma4(+) T cells also contribute to controlling CD8(+) T cell
      expansion and to regulating and reducing TNF-alpha secretion by activated CD8(+)
      T cells. This effect on TNF-alpha production was directly attributed to IL-10.
      These findings identify a novel mechanism by which pathogen-elicited CD8(+) T
      cells are regulated via interactions with, and activation of, IL-10-producing
      hepatoprotective gammadelta T cells.

PMID- 18624302
TI  - pK(a)-directed host-guest assemblies: rational analysis of molecular adducts of
      2,4-diamino-6-methyl-1,3,5-triazine with various aliphatic dicarboxylic acids.
AB  - Molecular adducts of 2,4-diamino-6-methyl-1,3,5-triazine (1) have been prepared
      with various aliphatic dicarboxylic acids. The molecular complexes (1 a-1 i) thus
      formed by co-crystallizing 1 with oxalic, malonic, succinic, fumaric, acetylene
      dicarboxylic, glutaric, thiodiglycolic, diglycolic, and adipic acids have been
      found to give two types of host-guest assemblies that have voids or channels in a
      three-dimensional arrangement. The different types of host-guest arrangement
      appear to result from differences in the acidity of the dicarboxylic acids, that
      is, acids with pK(a)<3.0 give host networks that consist of 1 and the
      corresponding acid with water or solvent molecules of crystallization present as
      guests, whereas acids with pK(a)>3.0 exist as guests in voids in a host network
      formed by 1. The former arrangement is observed in adducts 1 a, 1 b, 1 e, and 1 h
      and the latter arrangement is found in adducts 1 c, 1 d, 1 f, 1 g, and 1 i.

PMID- 18624304
TI  - A new zeolitic topology with sixteen-membered ring and multidimensional large
      pore channels.

PMID- 18624303
TI  - CC chemokine receptor 4 modulates Toll-like receptor 9-mediated innate immunity
      and signaling.
AB  - The present study addressed the modulatory role of CC chemokine receptor 4 (CCR4)
      in Toll-like receptor (TLR) 9-mediated innate immunity and explored the
      underlying molecular mechanisms. Our results demonstrated that CCR4-deficient
      mice were resistant to both septic peritonitis induced by cecal ligation and
      puncture (CLP) and CpG DNA/D-galactosamine-induced shock. In bone marrow-derived
      macrophages (BMMPhi) from CLP-treated CCR4-deficient mice, TLR9-mediated pathways
      of MAPK/AP-1, PI3K/Akt, and IkappaB kinase (IKK)/NF-kappaB were impaired compared
      to wild-type (WT) cells. While TLR9 expression was not altered, the intensity of
      internalized CpG DNA was increased in CCR4-deficient macrophages when compared to
      WT macrophages. Pharmacological inhibitor studies revealed that impaired
      activation of JNK, PI3K/Akt, and/or IKK/NF-kappaB could be responsible for
      decreased proinflammatory cytokine expression in CCR4-deficient macrophages.
      Interestingly, the CCR4-deficient BMMPhi exhibited an alternatively activated
      (M2) phenotype and the impaired TLR9-mediated signal transduction responses in
      CCR4-deficient cells were similar to the signaling responses observed in WT
      BMMPhi skewed to an alternatively activated phenotype. These results indicate
      that macrophages deficient in CCR4 impart a regulatory influence on TLR9-mediated
      innate immunity.

PMID- 18624306
TI  - Microfluidic self-patterning of large-scale crystalline nanoarrays for high
      throughput continuous DNA fractionation.

PMID- 18624305
TI  - Dysregulation of the host mevalonate pathway during early bacterial infection
      activates human TCR gamma delta cells.
AB  - Primates, but not rodents, have T cell receptor Vgamma9-Vdelta2 T cells bridging
      innate and adaptive antimicrobial immunity. This T cell population is activated
      by prenyl pyrophosphates isolated from microbial or eukaryotic cells. Although
      the microbial metabolites are more active than the cellular ones, their
      involvement in TCR gammadelta activation during infection has not been studied.
      Here, we show that, during the initial phases of infections with Escherichia coli
      and Staphylococcus aureus, TCR gammadelta cells are activated by endogenous
      mevalonate metabolites. Infections with low bacteria inocula up-regulate the
      production and accumulation of host-derived TCR gammadelta stimulatory antigens
      within 1 h, which is followed by a peak of TCR gammadelta cell activation at 5 h.
      Infections induce the accumulation and dephosphorylation of the
      hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme of the
      mevalonate pathway, resulting in increased activity of this enzyme and in
      increased synthesis of intermediate metabolites. Thus, primates have evolved the
      ability to readily respond to bacterial infection by sensing the dysregulation of
      the mevalonate pathway within infected cells, as a mechanism of immediate
      antimicrobial immunity.

PMID- 18624307
TI  - Intrasplenic trafficking of natural killer cells is redirected by chemokines upon
      inflammation.
AB  - The spleen is a major homing site for NK cells. How they traffic to and within
      this site in homeostatic or inflammatory conditions is, however, mostly unknown.
      Here we show that NK cells enter the spleen through the marginal sinus and home
      to the red pulp via a pertussis toxin-insensitive mechanism. Upon inflammation
      induced by poly(I:C) injection or mouse cytomegalovirus infection, many NK cells
      left the red pulp while others transiently entered the white pulp, predominantly
      the T cell area. This migration was dependent on both CXCR3 and CCL5, suggesting
      a synergy between CXCR3 and CCR5, and followed the path lined by fibroblastic
      reticular cells. Thus, the entry of NK cells in the white pulp is limited by the
      expression of pro-inflammatory chemokines. This phenomenon ensures the
      segregation of NK cells outside of the white pulp and might contribute to the
      control of immunopathology.

PMID- 18624308
TI  - Total synthesis of chondramide C and its binding mode to F-actin.

PMID- 18624309
TI  - Chondramide C: synthesis, configurational assignment, and structure-activity
      relationship studies.

PMID- 18624310
TI  - Concomitant and controllable chiral/racemic polymorphs: from achirality to
      isotactic, syndiotactic, and heterotactic chirality.

PMID- 18624311
TI  - Phosphorus-containing ligands for iron(III)-catalyzed atom transfer radical
      polymerization.

PMID- 18624312
TI  - Asymmetric catalysis: resin-bound hydroxyprolylthreonine derivatives in enamine
      mediated reactions.

PMID- 18624313
TI  - Synthesis of QS-21-xylose: establishment of the immunopotentiating activity of
      synthetic QS-21 adjuvant with a melanoma vaccine.

PMID- 18624314
TI  - Gold(I)-template catenane and rotaxane synthesis.

PMID- 18624315
TI  - Matter-wave metrology as a complementary tool for mass spectrometry.

PMID- 18624316
TI  - Photoswitching of basicity.

PMID- 18624318
TI  - Synthesis of indolines and tetrahydroisoquinolines from arylethylamines by Pd(II)
      catalyzed C-H activation reactions.

PMID- 18624317
TI  - A chiral Lewis acid strategy for enantioselective allylic C-H oxidation.

PMID- 18624319
TI  - Site-specific incorporation of methyl- and acetyl-lysine analogues into
      recombinant proteins.

PMID- 18624321
TI  - Mixing power, external convection, and effectiveness in bioreactors.
AB  - The phenomena of mixing and mass transfer of substrates to microorganisms greatly
      affect the biochemical reactions which take place in fermentation processes. The
      effect that agitation power has on the observable reaction kinetics involved in
      beer fermentation has been studied in different types of bioreactors, from
      laboratory to industrial scale. With this aim in mind, an effectiveness factor,
      eta, is introduced which is defined as the relation between the existing rate of
      reaction, whichever bioreactor is considered, and the reaction rate in the well
      mixed, and therefore presumably homogeneous, bioreactor with no diffusional
      limits. The limitation to homogeneously supplying nutrient material to the cells
      produces a decrease in this effectiveness factor, which has been correlated to
      the energy dissipation rate with a similar slope to that which appears in an
      existing correlation in the literature between this energy and the mass transfer
      coefficient. Additionally, a dimensionless reaction-convection number, N(RC),
      which is a function of the power input per unit volume, is proposed, which has
      been appropriately employed in correlating the effectiveness factor for the types
      of processes in which convection may be the key resistance factor.

PMID- 18624322
TI  - L-DOPA production from tyrosinase immobilized on nylon 6,6.
AB  - The production of L-DOPA immobilized on chemically modified nylon 6,6 membranes
      was studied in a batch reactor. Tyrosinase was immobilized on nylon using
      glutaraldehyde as a crosslinking agent. The effects of membrane pore size and
      glutaraldehyde concentration upon enzyme uptake and L-DOPA production were
      investigated. Enzyme uptake was unaffected by glutaraldehyde concentration;
      approximately 70% uptake was observed when 25% w/v (group 1), 5% (group 2), and
      3% (group 3) glutaraldehyde were used, indicating that glutaraldehyde was in
      excess. Similarly, uptake was the same for membranes with 0.20 and 10 microm pore
      sizes.Membranes produced using different levels of glutaraldehyde exhibited
      dramatically different capacities for L-DOPA production, despite the fact that
      enzyme uptake was equivalent. Membranes from groups 2 and 3 (5% and 3%
      glutaraldehyde) produced L-DOPA at a rate of 1.70 mg L(-1) h(-1) over 170 h in a
      500-mL batch reactor. However, no free L-DOPA was detected when group 1 membranes
      were used. Experimental evidence suggests that L-DOPA was produced, but remained
      bound to these membranes via excess glutaraldehyde left over from the
      immobilization process. Membrane pore size also effected L-DOPA production; less
      production was observed when 10-microm membranes were used, despite equivalent
      enzyme uptake. The observed difference in production may be due to differences in
      the pore density on the two types of membranes which could affect the access of
      the substrate to the immobilized enzyme.The results of these studies indicate
      that tyrosinase can be effectively immobilized on nylon 6,6. L-DOPA production
      was optimal when 0.20-microm-pore-size membranes were activated with 3-5%
      glutaraldehyde. Stability studies indicated a 20% reduction in activity over 14
      days when the immobilized enzyme was used under turnover conditions.

PMID- 18624323
TI  - Surfactant enhancement of (S)-naproxen ester productivity from racemic naproxen
      by lipase in isooctane.
AB  - In the enantioselective esterification of racemic Naproxen with trimethylsilyl
      methanol in isooctane by Candida cylindracea lipase, improvements in (S)-naproxen
      ester productivity and enzyme selectivity were demonstrated by adding bis(2
      ethylhexyl) sodium sulfosuccinate (AOT) as the best surfactant. The effect of
      water content on the enhancement of enzyme activity was elucidated from the
      reduced adsorption of surfactant molecules on the lipase. A competitive
      inhibition by the alcohol and a noncompetitive inhibition by the surfactant to
      the enzyme were found from the kinetic analysis. By using a two-phase extraction,
      a complete separation of the surfactant from the organic solution was obtained.

PMID- 18624324
TI  - Microencapsulation of recombinant Saccharomyces cerevisiae cells with invertase
      activity in liquid-core alginate capsules.
AB  - As a means of integrating cell growth and immobilization, recombinant
      Saccharomyces cerevisiae cells with invertase activity were immobilized in liquid
      core alginate capsules and cultured to a high density. S. cerevisiae cells of SEY
      2102 (MAT alpha ura3-52 leu2-3, 112 his4-519) harboring plasmid pRB58 with the
      SUC2 gene coding for invertase were grown to 83 g/L of liquid-core volume inside
      the capsule on a dry weight basis. The cloned invertase was expressed well in the
      immobilized cells with slightly higher activity than the free cells in a batch
      culture. Invertase in the immobilized cells showed slightly more improved thermal
      stability than in the free cells. Storage in a Na-acetate buffer at 4 degrees C
      and 10 degrees C for 1 month resulted in 7% and 8% loss in activity,
      respectively. The sucrose hydrolysis reaction was stably maintained for 25
      repeated batches for 7 days at 30 degrees C. Continuous hydrolysis of 0.3 M
      sucrose was carried out in a packed bed reactor with a conversion of more than
      90% at a maximum productivity of 55.5 g glucose/L per hour for 7 days. In a
      continuous stirred tank reactor, the maximum productivity of 80.8 g glucose/L per
      hour was achieved at a conversion of 59.1% using 1.0 M sucrose solution, and 0.5
      M sucrose solution was hydrolyzed for 1 week with a 95% conversion at a
      productivity of 48.8 g/L per hour.

PMID- 18624325
TI  - Sequential actions of glucose oxidase and peroxidase in molecular films assembled
      by layer-by-layer alternate adsorption.
AB  - Molecular films of protein/polyion layers were assembled by means of alternate
      adsorption through electrostatic interaction. Glucose oxidase (GOD) and
      peroxidase (POD) were assembled in combination with sodium poly(styrenesulfonate)
      (PSS) and poly(ethyleneimine) (PEI), respectively. Enzyme activities of those
      films on specific substrates (glucose and H(2)O(2)) were examined by coloring
      reaction of dye DA67. A multienzyme film containing GOD layer and POD layer was
      prepared by alternate adsorption of POD/PSS followed by PEI/GOD. Sequential redox
      reaction of glucose/H(2)O(2)/DA67 was demonstrated successfully with this
      supramolecular system.

PMID- 18624326
TI  - Pathway kinetics and metabolic control analysis of a high-yielding strain of
      Penicillium chrysogenum during fed batch cultivations.
AB  - A kinetic model representing the pathway for the biosynthesis of penicillin by P.
      chrysogenum has been developed. The model is capable of describing the flux
      through the biosynthetic pathway, and model simulations correspond well with
      measurements of intermediates and end products. One feature of the present model
      structure is that it assumes the kinetics of the enzyme isopenicillin N
      synthetase (IPNS) to be first order with respect to the dissolved oxygen
      concentration in the range of 0.070 to 0.18 mM (25% to 70% saturation with air).
      Thus, it indicates the importance that molecular oxygen has on the rate of the
      reaction catalyzed by this enzyme, and consequently as an enhancer of the
      specific rate of penicillin production. Using the kinetic model, metabolic
      control analysis (MCA) of the pathway was performed. The determined flux control
      coefficients suggested that, during the production phase, the flux is controlled
      by IPNS as this enzyme becomes saturated with tripeptide delta-(L-alpha-amino
      adipyl)-L-cysteinyl-D-valine (LLD-ACV). In the simulations, oxygen was shown to
      be a bottleneck alleviator by stimulating the rate of IPNS which prevents the
      accumulation of LLD-ACV. As a consequence of this stimulation, the rate
      controlling step was moved to another place in the pathway.

PMID- 18624327
TI  - Metabolic flux distribution in Corynebacterium melassecola ATCC 17965 for various
      carbon sources.
AB  - The distribution of carbon in the metabolic network of a bacterial cell was
      estimated by a mass-balance-based intracellular flux computation method. It was
      applied to the growth phase of Corynebacterium melassecola, a glutamic acid
      producing bacterium, using experimental production yields of biomass, lactate and
      acetate measured during batch cultures on glucose, fructose, and various mixtures
      of both sugars. This flux computation method identifies the direction of the 86
      reactions that ensure proper metabolic function during the growth phase of C.
      melassecola. Flux ratios allow comparison of calculated and relevant experimental
      yields. The results highlight the key influence of the biomass production yield
      Y(X-O(2) ) on the overall distribution of carbon; the proportion of carbon
      drained in the pentose-P pathway fell from a value in the range of 54% to 47% on
      media containing glucose (Y(X-O(2) ) = 1.75 to 1.56 g X/g O(2)) to 37% on
      fructose medium (Y(X-O(2) ) = 1.36 g X/g O(2)). The highest maintenance
      requirement was calculated on fructose medium (J(m) = 290 mol ATP/100 mol
      fructose) which must be connected to a lower efficiency of cell multiplication
      observed on this substrate. Another important result was that the significant
      decreases in experimental values of production yields and rates observed on
      fructose medium which were related to the operation of the FBPase. In particular,
      it was estimated that, as long as the proportion of glucose in the carbon source
      remains above 22% (78% fructose), the operation of the FBPase is not necessary
      and the bacteria exhibit behavior similar to that observed on glucose alone; this
      result is consistent with experimental observations.

PMID- 18624328
TI  - Control of glycolytic flux in Zymomonas mobilis by glucose 6-phosphate
      dehydrogenase activity.
AB  - Glycolytic genes in Zymomonas mobilis are highly expressed and constitute half of
      the cytoplasmic protein. The first four genes (glf, zwf, edd, glk) in this
      pathway form an operon encoding a glucose permease, glucose 6-phosphate
      dehydrogenase (G6-P dehydrogenase), 6-phosphogluconate dehydratase, and
      glucokinase, respectively. Each gene was overexpressed from a tac promoter to
      investigate the control of glycolysis during the early stages of batch
      fermentation when flux (qCO(2)) is highest. Almost half of flux control appears
      to reside with G6-P dehydrogenase (C(J) (G6-P dehydrogenase) = 0.4). Although Z.
      mobilis exhibits one of the highest rates of glycolysis known, recombinants with
      elevated G6-P dehydrogenase had a 10% to 13% higher glycolytic flux than the
      native organism. A small increase in flux was also observed for recombinants
      expressing glf. Results obtained did not allow a critical evaluation of
      glucokinase and this enzyme may also represent an important control point. 6
      Phosphogluconate dehydratase appears to be saturating at native levels. With
      constructs containing the full operon, growth rate and flux were both reduced,
      complicating interpretations. However, results obtained were also consistent with
      G6-P dehydrogenase as a primary site of control. Flux was 17% higher in operon
      constructs which exhibited a 17% increase in G6-P dehydrogenase specific
      activity, relative to the average of other operon constructs which contain a
      frameshift mutation in zwf. It is unlikely that all flux control residues solely
      in G6-P dehydrogenase (calculated C(J) (G6-P dehydrogenase) = 1.0) although these
      results further support the importance of this enzyme. As reported in previous
      studies, changes in flux were not accompanied by changes in growth rate providing
      further evidence that ATP production does not limit biosynthesis in rich complex
      medium.

PMID- 18624329
TI  - Thermodynamic analysis of trinitrotoluene biodegradation and mineralization
      pathways.
AB  - Biodegradation of 2,4,6-trinitrotoluene (TNT) proceeds through several different
      metabolic pathways. However, the reaction steps which are considered rate
      controlling have not been fully determined. Glycolysis and other biological
      pathways contain biochemical reactions which are acutely rate-limiting due to
      enzyme control. These rate-limiting steps also have large negative Gibbs free
      energy changes. Because xenobiotic compounds such as TNT can be used by
      biological systems as nitrogen, carbon, and energy sources, it is likely that
      their degradation pathways also contain acutely rate-limiting steps.
      Identification of these rate-controlling reactions will enhance and better direct
      genetic engineering techniques to increase specific enzyme levels.This article
      identifies likely rate-controlling steps (or sets of steps) in reported TNT
      biodegradation pathways by estimating the Gibbs free energy change for each step
      and for the overall pathways. The biological standard Gibbs free energy change of
      reaction was calculated for each pathway step using a group contribution method
      specifically tailored for biomolecules. The method was also applied to
      hypothetical "pathways" constructed to mineralize TNT using several different
      microorganisms. Pathways steps that have large negative Gibbs free energy changes
      are postulated to be potentially rate-controlling. The microorganisms which
      utilize degradation pathways with the largest overall (from TNT to citrate)
      negatiave Gibbs free energy changes were also determined. Such microorganisms can
      extract more energy from the starting substrate and are thus assumed to have a
      competitive advantage over other microorganisms. Results from this modeling-based
      research are consistent with much experimental work available in the literature.

PMID- 18624330
TI  - On-line estimation of the biomass activity during animal-cell cultivations.
AB  - A software sensor was developed to determine the volumetric biomass activity of
      animal cell cultivations on-line. It was based on the on-line estimation of the
      ATP-production rate from the oxygen uptake and the lactic-acid production rate.
      The sensor was verified for a batch culture of Vero cells, and a batch and a
      continuous culture of hybridoma cells. For the hybridoma cells, the sensor showed
      a good correlation with the biomass concentration. However, this was not the case
      for the Vero cells. As soon as glutamine was exhausted, the biomass activity
      stabilized, whereas the amount of biomass almost doubled. Because the sensor
      developed responds to nutrient limitations much faster than becomes visible
      through cell density measurements, and because the volumetric biomass activity
      can be related to the volumetric consumption rates and production rates of
      important metabolites, it shows excellent possibilities for control purposes.

PMID- 18624331
TI  - Kinetics of glucose oxidase excretion by recombinant Aspergillus niger.
AB  - The kinetics of glucose oxidase (GOD) excretion by recombinant Aspergillus niger
      NRRL-3 (GOD3-18) were investigated using enzymatic activity measurements as well
      as gel electrophoresis techniques. The majority of GOD was produced during rapid
      growth in the first phase of the cultivation. The high excretion rate during this
      phase did not prevent the endocellular accumulation of GOD up to 40% of the total
      soluble cell protein demonstrating that the production rate exceeded the
      excretion rate of the enzyme into the culture medium. During the second phase of
      the cultivation, excretion of GOD occurred at a slower rate, although the
      majority of GOD produced during the first phase was excreted during the second
      phase of the cultivation. At the end, about 90% of the total GOD produced was
      recovered from the culture medium. Two-dimensional gel electrophoresis provided
      evidence that endo- and exocellular GOD were indistinguishable, revealing
      identical posttranslational modifications (e.g., signal sequence cleavage,
      glycosylation pattern). The results demonstrate that the initial steps of the
      secretory pathway are fast and that the excretion of the enzyme into the culture
      fluid was most likely delayed due to retention by the cell wall.

PMID- 18624332
TI  - Affinity precipitation and site-specific immobilization of proteins carrying
      polyhistidine tails.
AB  - Proteins carrying genetically attached polyhistidine tails have been purified
      using affinity precipitation with metal chelates. DNA fragments encoding four or
      five histidine residues have been genetically fused to the oligomeric enzymes
      lactate dehydrogenase (Bacillus stearothermophilus), beta-glucoronidase
      (Escherichia coli), and galactose dehydrogenase (Pseudomonas fluorescens) as well
      as to the monomeric protein A (Staphylococcus aureus). The chimeric genes were
      subsequently expressed in E. coli. The engineered enzymes were successfully
      purified from crude protein solutions using ethylene glycolbis (beta-aminoethyl)
      tetraacetic acid (EGTA) charged with Zn(2+) as precipitant, whereas protein A,
      carrying only one attached histidine tail, did not precipitate. However, all of
      the engineered proteins could be purified on immobilized metal affinity
      chromatography (IMAC) columns loaded with Zn(2+). The potential of using the same
      histidine tails for site-specific immobilization of proteins was also
      investigated. The enzymes were all catalytically active when immobilized on IMAC
      gels. For instance, immobilized lactate dehydrogenase, carrying tails composed of
      four histidine residues, displaced 83% of the soluble enzyme activity.

PMID- 18624333
TI  - Effect of particle loading on GM-CSF production by Saccharomyces cerevisiae in a
      three-phase fluidized bed bioreactor.
AB  - Continuous production of a recombinant murine granulocyte-macrophage colony
      stimulating factor (MuGM-CSF) by immobilized yeast cells, Saccharomyces
      cerevisiae strain XV2181 (a/a, Trp1) containing plasmid palphaADH2, in a
      fluidized bed bioreactor was studied at a 0.03 h(-1) dilution rate and various
      particle loading rates ranging from 5% to 33% (v/v). Cells were immobilized on
      porous glass beads fluidized in an air-lift draft tube bioreactor. A selective
      medium containing glucose was used to start up the reactor. After reaching a
      stable cell concentration, the reactor feed was switched to a rich, nonselective
      medium containing ethanol as the carbon source for GM-CSF production. GM-CSF
      production increased initially and then dropped gradually to a stable level.
      During the same period, the fraction of plasmid-carrying cells declined
      continuously to a lower level, depending on the particle loading. The relatively
      stable GM-CSF production, despite the large decline in the fraction of plasmid
      carrying cells, was attributed to cell immobilization. As the particle loading
      rate increased, the plasmid stability also increased. Also, as the particle
      loading increased from 5% to 33%, total cell density in the bioreactor increased
      from 16 to 36 g/L, and reactor volumetric productivity increased from 0.36 to
      1.31 mg/L.h. However, the specific productivity of plasmid-carrying cells
      decreased from 0.55 to 0.07 mg/L.g cell. The decreased specific productivity at
      higher particle loading rates was attributed to reduced growth efficiency caused
      by nutrient limitations at higher cell densities. Both the reactor productivity
      and specific cell productivity increased by two- to threefold or higher when the
      dilution rate was increased from 0.03 to 0.07 h(-1).

PMID- 18624334
TI  - Biosorption of uranium by Pseudomonas aeruginosa strain CSU: characterization and
      comparison studies.
AB  - Pseudomonas aeruginosa strain CSU, a nongenetically engineered bacterial strain
      known to bind dissolved hexavalent uranium (as UO(2) (2+) and/or its cationic
      hydroxo complexes), was characterized with respect to its sorptive activity
      (equilibrium and dynamics). Living, heat-killed, permeabilized, and
      unreconstituted lyophilized cells were all capable of binding uranium. The
      uranium biosorption equilibrium could be described by the Langmuir isotherm. The
      rate of uranium adsorption increased following permeabilization of the outer
      and/or cytoplasmic membrane by organic solvents such as acetone. P. aeruginosa
      CSU biomass was significantly more sorptive toward uranium than certain novel,
      patented biosorbents derived from algal or fungal biomass sources. P. aeruginosa
      CSU biomass was also competitive with commercial cation-exchange resins,
      particularly in the presence of dissolved transition metals. Uranium binding by
      P. aeruginosa CSU was clearly pH dependent. Uranium loading capacity increased
      with increasing pH under acidic conditions, presumably as a function of uranium
      speciation and due to the H(+) competition at some binding sites. Nevertheless,
      preliminary evidence suggests that this microorganism is also capable of binding
      anionic hexavalent uranium complexes. Ferric iron was a strong inhibitor of
      uranium binding to P. aeruginosa CSU biomass, and the presence of uranium also
      decreased the Fe(3+) loading when the biomass was not saturated with Fe(3+),
      suggesting that Fe(3+) and uranium may share the same binding sites on biomass.
      Although the equilibrium loading capacity of uranium was greater than that of
      Fe(3+), this biomass showed preference of binding Fe(3+) over uranium. Thus, a
      two-stage process in which iron and uranium are removed in consecutive steps was
      proposed for efficient use of the biomass as a biosorbent in uranium removal from
      mine wastewater, especially acidic leachates.

PMID- 18624337
TI  - Waste biotech.

PMID- 18624341
TI  - Biotech round the world: focus on Canada.

PMID- 18624343
TI  - Folding at the rhythm of the rare codon beat.
AB  - The persistent difficulties in the production of protein at high levels in
      heterologous systems, as well as the inability to understand pathologies
      associated with protein aggregation, highlight our limited knowledge on the
      mechanisms of protein folding in vivo. Attempts to improve yield and quality of
      recombinant proteins are diverse, frequently involving optimization of the cell
      growth temperature, the use of synonymous codons and/or the co-expression of
      tRNAs, chaperones and folding catalysts among others. Although protein secondary
      structure can be determined largely by the amino acid sequence, protein folding
      within the cell is affected by a range of factors beyond amino acid sequence. The
      folding pathway of a nascent polypeptide can be affected by transient
      interactions with other proteins and ligands, the ribosome, translocation through
      a pore membrane, redox conditions, among others. The translation rate as well as
      the translation machinery itself can dramatically affect protein folding, and
      thus the structure and function of the protein product. This review addresses
      current efforts to better understand how the use of synonymous codons in the mRNA
      and the availability of tRNAs can modulate translation kinetics, affecting the
      folding, the structure and the biological activity of proteins.

PMID- 18624347
TI  - Now we are talking sense! Functional approaches to novel nutraceuticals and
      cosmeceuticals.

PMID- 18624348
TI  - Herb-drug interactions: theory versus practice.

PMID- 18624349
TI  - Efficient antitumor immunity in a murine colorectal cancer model induced by CEA
      RNA-electroporated B cells.
AB  - RNA electroporation as a gene delivery method is more feasible and safer as
      compared with viral vectors. RNA-loaded dendritic cells (DC) have been used to
      induce T cell responses against tumor rejection antigens and B cells can also act
      as antigen-presenting cells for cellular vaccines. In this study, we compared B
      cells and DC, after electroporation with carcinoembryonic antigen (CEA) RNA, for
      their capacity to generate cytotoxic T lymphocytes and antitumor immunity.
      Vaccination using these B cells induced levels of IFN-gamma-secreting T cells and
      cytotoxic T cells comparable to those induced by DC. Intravenous administration
      was the optimum route for the B cell vaccine, while subcutaneous administration
      was the optimum route for the DC vaccine. The B cell vaccine predominantly
      generated CEA-specific CD4(+) T cells, whereas the DC vaccine generated CD8(+) T
      cells. Moreover, the B cell vaccine induced higher levels of anti-CEA antibodies
      than the DC vaccine. A heterogeneous prime-boost using B cells and DC failed to
      show any synergistic effects; however, the B cell vaccine did inhibit tumor
      growth and prolonged survival to a similar extent as the DC vaccine. Such RNA
      electroporated B cells may prove useful as cellular tumor vaccines with potential
      clinical application.

PMID- 18624350
TI  - Microsomal triglyceride transfer protein regulates endogenous and exogenous
      antigen presentation by group 1 CD1 molecules.
AB  - Lipid antigens are presented to T cells by the non-polymorphic MHC class I
      related CD1 molecules. Microsomal triglyceride transfer protein (MTP) is an
      endoplasmic reticulum (ER)-resident chaperone that has been shown to lipidate the
      group 2 CD1 molecule CD1d and thus to regulate its function. We now report that
      MTP also regulates the function of group 1 CD1 molecules CD1a, CD1b, and CD1c.
      Pharmacological inhibition of MTP in monocyte-derived dendritic cells and
      lymphoblastoid B cell lines transfected with group 1 CD1 resulted in a
      substantial decrease in endogenous self lipid antigen presentation to several CD1
      restricted T cell lines. Silencing MTP expression in CD1c-transfected HeLa cells
      similarly resulted in decreased self reactivity. Unexpectedly, inhibition of ER
      resident MTP, which was confirmed by confocal microscopy, also markedly decreased
      presentation of exogenous, endosomally loaded, mycobacterial lipid antigens by
      CD1a and CD1c to T cells. Thus, these studies indicate that MTP, despite its ER
      localization, regulates endogenous as well as exogenous lipid antigen
      presentation, and suggest a broad role for MTP in the regulation of CD1 antigen
      presentation.

PMID- 18624351
TI  - Deficiency of Act1, a critical modulator of B cell function, leads to development
      of Sjogren's syndrome.
AB  - CD40L and B lymphocyte-activating factor (BAFF), members of the TNF superfamily,
      play critical roles in B cell survival and activation, and in the regulation of
      humoral immunity. We previously reported that the adaptor molecule Act1 functions
      as a negative regulator of CD40- and BAFF-mediated B cell survival. Here we
      demonstrated that mice deficient in Act1 developed systemic autoimmune disease
      with histological and serological features of human Sjogren's syndrome (SS), in
      association with systemic lupus erythematosus-like nephritis. Analyses of Act1(-/
      )CD40(-/-) and Act1(-/-)BAFF(-/-) double-deficient mice revealed that Act1
      regulates different stages of the disease development through its impact on both
      CD40- and BAFF-mediated pathways. We found that Act1 modulates the survival of
      autoreactive B cells mainly through its negative regulatory role in BAFF-mediated
      cell survival, while the effect of Act1 on autoantibody production is likely
      through modulation of CD40-mediated T cell-dependent antibody response. The
      impact of Act1 on both BAFF and CD40 pathways establishes Act1-deficient mice as
      a unique model to study distinct steps of autoimmunity and regulation of self
      tolerance.

PMID- 18624353
TI  - Regenerative medicine and stem cell based drug discovery.
AB  - As William Shakespeare beautifully described, increasing age often causes loss of
      tissue and organ function. The increase in average life expectancy in many
      countries is generating an aging society and an increase in age-related health
      problems. Regenerative medicine is expected to be a powerful actor in this drama,
      and stem cell technology may hold the key to the development of innovative
      treatments for acute and chronic degenerative conditions. This Review surveys the
      present situation and some future prospects for regenerative medicine and stem
      cell based drug discovery.

PMID- 18624354
TI  - Endogenous presentation of a nuclear antigen on MHC class II by autophagy in the
      absence of CRM1-mediated nuclear export.
AB  - Accumulating evidence suggests that intracellular antigens are endogenously
      presented on MHC class II, but it is still unknown whether antigens within
      different subcellular compartments are presented with similar efficiency, and via
      the same or different pathways. We have previously shown that endogenous MHC
      class II presentation of the cytosolic bacterial antigen neomycin
      phosphotransferase II (NeoR) is mediated by autophagy. Here, we addressed whether
      secluding NeoR from this cytoplasmic pathway by directing the protein into the
      cell nucleus (NucNeoR) would affect antigen presentation. Unexpectedly, NucNeoR
      was presented at least as efficiently as the cytosolic version of the antigen.
      Furthermore, presentation of NucNeoR was also dependent on autophagocytosis and
      lysosomal processing, indicating that both antigens were presented via the same
      pathway. Inhibition of CRM1-mediated nuclear export did not impede antigen
      presentation, indicating that NucNeoR gained access to this autophagy-dependent
      MHC class II presentation pathway by a CRM1-independent route. Thus, this
      endogenous presentation pathway broadens the spectrum of intracellular antigens
      surveyed by CD4(+) T cells by efficiently sampling cytoplasmic as well as nuclear
      antigens.

PMID- 18624355
TI  - Engagement of Toll-like receptor 2 in mouse macrophages infected with
      Mycobacterium avium induces non-oxidative and TNF-independent anti-mycobacterial
      activity.
AB  - Toll-like receptor (TLR) 2 plays an important role in the immune response to
      mycobacterial infections, being required for optimal immunity against certain
      virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the
      intra-macrophagic growth of M. avium, using macrophages from TLR2-deficient mice.
      We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced
      bacteriostasis of M. avium inside bone marrow-derived macrophages in a MyD88
      dependent way. Additionally, lipoproteins from the cell envelope of M. avium with
      a molecular mass of 20-25 kDa triggered this TLR2 pathway, leading to a decrease
      in the growth of the mycobacteria. Although TLR2 engagement induced the
      production of TNF, this cytokine as well as nitric oxide and superoxide molecules
      were not necessary for TLR2-mediated bacteriostasis. Finally, TLR ligation did
      not induce the expression of the 47-kDa guanosine triphosphatase (LRG-47) but it
      promoted an increased maturation of the phagosome with regards to acquisition of
      LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as-yet
      unknown mechanism that may involve increased phagosome maturation.

PMID- 18624358
TI  - Modeling the enzymatic transformation of 3,5-dimethoxy,4-hydroxy cinnamic acid by
      polyphenoloxidase from the white-rot fungus Trametes versicolor.
AB  - A mechanism for transforming sinapic acid by a polyphenoloxidase from Trametes
      versicolor was investigated using changes in sinapic acid and oxygen
      concentrations during the reaction. The experiments were performed in a closed
      system without supplemental oxygen. The effects of temperature and initial oxygen
      concentration on the reaction rates were examined. To compare the obtained
      results with those from spectrophotometric studies, some runs were performed
      using an open system with supplemental oxygen. Sinapic acid transformation can be
      described by the Theorell-Chance Bi-Bi or Ordered Bi-Bi mechanisms. This reacting
      system consisted also of additional enzymatic reactions between the products of
      sinapic acid transformation and oxygen. A mathematical model was developed using
      four ordinary differential equations that represent the Theorell-Chance Bi-Bi
      mechanism with three alternate substrates. Model parameters (i.e., rate
      constants) were determined using the data collected at three different
      temperatures. On the basis of the transition state theory, relationships between
      these constants and temperature were established. It is shown that, in the open
      system, the observed change in the enzyme activity at higher temperatures was
      caused by two opposing phenomena: an Arrhenius effect which increased the rate,
      and a solubility effect which reduced the rate due to a lower oxygen
      concentration. This finding allows us to recommend better conditions for
      spectrophotometric methods, the assay most commonly used to evaluate this and
      similar enzymes.

PMID- 18624356
TI  - The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta
      secretion but dispensable for adjuvant activity.
AB  - Aluminum hydroxide (alum) is the most widely used adjuvant in human vaccines, but
      the immune mechanisms that are activated by alum remain poorly understood. Alum
      has recently been shown to promote caspase-1 activation and IL-1beta secretion,
      but the cellular pathways involved remain elusive. Here we report that the
      release of IL-1beta triggered by alum is abrogated in macrophages deficient in
      the NLR family, pyrin domain containing 3 (Nlrp3) protein and the apoptosis
      associated speck-like protein containing a caspase recruitment domain (Asc) but
      not the NLR family, CARD domain containing 4 (Nlrc4) protein. The requirement of
      the Nlrp3 inflammasome was specific for IL-1beta in that secretion of TNF-alpha
      was independent of Nlrp3 or Asc. Consistently, processing of pro-caspase-1
      induced by alum was abolished in macrophages lacking Nlrp3 or Asc. Unlike caspase
      1 processing and IL-1beta secretion triggered by LPS, alum-mediated activation of
      the inflammasome did not require exogenous ATP. Importantly, induction of IgG
      production against human serum albumin by alum was unimpaired in mice deficient
      in Nlrp3. These results indicate that alum induces IL-1beta via the Nlrp3
      inflammasome but this activity is dispensable for alum-mediated adjuvant
      activity.

PMID- 18624359
TI  - Membrane adsorption characteristics determine the kinetics of flow-through
      transductions.
AB  - Retrovirus-mediated gene transfer is currently limited by random Brownian motion
      of the retrovirus. This limitation can be overcome by flowing the retrovirus
      solution through a porous membrane that supports the target cells, leading to a
      significant increase in the transduction efficiency. This procedure is termed
      "flow-through transduction." In this study, we characterized the effects of the
      fluid flowrate and the influence that membrane characteristics have on the flow
      through transduction procedure. The transduction efficiencies increased with
      flowrate until a plateau was reached at average flow velocities exceeding 0.3
      cm/h for flow times of 3 to 4 h, using a collagen-coated depth (COL) membrane. A
      correlation between the optimal time for maximal gene transfer using flow-through
      transductions and the optimal time for maximal virus activity on the membrane was
      found, suggesting that the membrane adsorption capacity for virus determined the
      amount of gene transfer that could occur.Membrane adsorption characteristics were
      further investigated using two different membrane types: a tracketched polyester
      screen (PE) membrane and the COL membrane. Flow-through transductions using the
      PE and COL membranes showed that a high level of gene transfer could be attained
      using the COL membrane while the PE membrane gave much lower transduction
      efficiencies. The addition of the polycation polybrene (PB) changed these results
      markedly, making transductions achieved on the PE membrane similar in number to
      those obtained on the COL membrane. Since PB is believed to influence the virus
      adsorption to PE membrane, these results further support the conclusion that the
      increase in gene transfer achieved by the flow-through transduction procedure is
      due to virus adsorption to the membrane. The flow-through transduction procedure
      thus leads to co-localization of the viral vector and the target cell that in
      turn leads to a high transduction efficiency.

PMID- 18624360
TI  - Secretion of recombinant proteins from hydroxyethyl methacrylate-methyl
      methacrylate capsules.
AB  - Current human gene therapy relies on genetic modification of the patient's own
      cells. An alternate nonautologous approach is to use universal cell lines
      engineered to secrete therapeutic products. Protection with immunoisolation
      devices before implantation would allow the use of the same recombinant cell line
      for treating different patients, thus potentially lowering the cost of treatment.
      To study the properties of a mechanically stable synthetic biomaterial,
      hydroxyethyl methyacrylate-methyl methacrylate (HEMA-MMA) as the immuno-isolation
      device, we encapsulated recombinant mouse fibroblast cells engineered to secrete
      products ranging from 27 to 300 kDa in size (human growth hormone, mouse beta
      hexosaminidase and beta-glucuronidase) in the presence or absence of the
      extracellular matrix Matrigel. Both viability and cell number in the
      microcapsules increased with time after encapsulation and cell morphology
      indicated viable cell growth, thus showing that the capsule membrane barrier was
      compatible with nutrient/waste exchange necessary for normal metabolic
      activity.The intracellular levels of these recombinant gene products were
      constant throughout the experimental period of 22 days in the presence or absence
      of Matrigel, thus demonstrating that the microenvironment did not lead to
      downregulation of the transgenes. However, the extracellular levels of the gene
      products secreted from the cells and trapped within the microcapsules were
      dependent on the molecular size of the product and presence of Matrigel. With the
      27-kDa human growth hormone, the presence of Matrigel caused its retention within
      this intracapsular space, but its release from the microcapsules to the culture
      medium was not impeded. With the 120-kDa beta-hexosaminidase or the 300-kDa beta
      glucuronidase, they were retained within the microcapsule space regardless of the
      presence or absence of Matrigel, and their passage from the microcapsules to the
      media was totally blocked. In conclusion, the HEMA-MMA microcapsules are
      supportive of recombinant cell growth and maintained their molecular cutoff at
      approximately 100 kDa. Inclusion of extracellular matrix was unable to improve
      cell growth and may impede the exit of some gene products.

PMID- 18624361
TI  - Intracellular receptor/ligand sorting based on endosomal retention components.
AB  - Endocytosed molecules are sorted in endosomes to different cellular destinations
      (e.g., to lysosomes or to the plasma membrane). Diverse endosomal sorting results
      have been reported for different ligands and receptors in a variety of cell
      types, but the general principles governing these sorting outcomes are not well
      understood. For example, we observed a wide range of sorting outcomes with the
      epidermal growth factor (EGF)/receptor system in fibroblasts using several
      members of the EGF family and site-directed ligand and receptor mutants. In this
      article we describe a mechanistic mathematical model of endosomal sorting based
      on the hypothesis that receptors may be selectively retained by the endosomal
      sorting apparatus and that this process may be modulated by receptor occupancy.
      Our results show that this single mechanism can account for the wide variety of
      observed sorting outcomes. By providing a conceptual framework for understanding
      endosomal sorting, this model not only helps interpret our experimental results
      for the EGF/receptor system, but also provides some insight into the principles
      governing sorting. For example, the model predicts that the influence of
      selective endosomal retention of receptor/ligand complexes is seen in deviations
      of ligand sorting outcomes from pure fluid phase sorting behavior. Furthermore,
      the model suggests that selective endosomal retention of complexes within
      endosomes gives rise to three sorting regimes characterized by distinguishable
      qualitative trends in the dependence of ligand sorting fractions on intracellular
      ligand concentrations.

PMID- 18624362
TI  - NSO myeloma cell death: Influence of bcl-2 overexpression.
AB  - The productivity of recombinant mammalian cell lines growth in batch culture is
      often limited by the rapidity with which cells die on entry into the decline
      phase (the period of culture after the maximum cell density has been reached and
      where cell viability begins to fall). We examined the decline phase
      characteristics of the NSO myeloma cell line with a view to modulating the cell
      death that ensues. Examination of nuclear morphology during culture revealed that
      the onset of the decline phase was marked by a time-dependent increase in the
      percentage of cells that exhibited condensed and fragmented nuclei. Furthermore,
      these changes coincided with a fall in DNA integrity. High molecular weight DNA
      appeared to be degraded into oligonucleosomal fragments. Taken together, these
      observations indicated that NSO cells die by the process of apoptosis. The
      protein encoded by the bcl-2 gene has been shown to counter apoptosis induced by
      a large variety of stimuli and in a number of different cell types, but is not
      expressed in NSO cells. We examined whether overexpression of this protein could
      prevent/delay the onset of cell death seen during batch culture and also in
      response to serum limitation. Bcl-2 failed to affect the decline phase
      characteristics and serum dependence of NSO cells. In our search to explain these
      findings, we found that the NSO cell line expresses bax and also a high level of
      another Bcl-2 related protein, Bcl-x(L). Given that Bcl-X(L) is a sequence and
      functional homologue of Bcl-2, it is possible that Bcl-2 is redundant in the NSO
      cell background. These data therefore indicate that cells such as NSO, which are
      used in biotechnologically important processes such as generation of hybridomas
      and expression of recombinant proteins, may express only a subset of genes
      important in apoptotic regulation. Modulation of the death characteristics of
      such cells will need to take account of the expression profile of such genes and
      their regulatory interactions.

PMID- 18624363
TI  - ATP regeneration by thermostable ATP synthase.
AB  - We investigated the possibility of using thermostable ATP synthase (TF(0)F(1))
      for a new ATP regeneration method. TF(0)F(1) was purified from a thermophilic
      bacterium, PS3, and reconstituted into liposomes. ATP synthesis experiments
      showed that TF(0)F(1) liposomes could synthesize ATP in micromole concentrations
      by acid-base change. The acid-base change was repeated six times over an 11-day
      period with no detectable loss of activity at the reaction temperature (45
      degrees C). Given these encouraging results, we conceptualized and modeled a
      system to synthesize ATP using ATP synthase with energy supplied by acid-base
      change. In this system, liposomes containing ATP synthase are immobilized on
      small glass spheres that facilitate separation of buffers from the liposomes
      after the acid-base change. Compared to an alternate system that uses membranes
      to separate the buffers from the liposomes, the glass spheres reduce inefficient
      mixing of acidic and basic buffers during the acid-base change. To increase the
      ATP synthesis yield, this system uses electrodialysis to regenerate a potassium
      gradient after the acid-base change. It also employs water-splitting
      electrodialysis to regenerate KOH and HCl required to adjust the pH of acidic and
      basic buffers. All reagents are recycled, so electrical energy is the only
      required input.

PMID- 18624364
TI  - Xylitol production by immobilized recombinant Saccharomyces cerevisiae in a
      continuous packed-bed bioreactor.
AB  - Continuous xylitol production with two different immobilized recombinant
      Saccharomyces cerevisiae strains (H475 and S641), expressing low and high xylose
      reductase (XR) activities, was investigated in a lab-scale packed-bed bioreactor.
      The effect of hydraulic residence time (HRT; 1.3-11.3 h), substrate/cosubstrate
      ratio (0.5 and 1), recycling ratio (0, 5, and 10), and aeration (anaerobic and
      oxygen limited conditions) were studied. The cells were immobilized by gel
      entrapment using Ca-alginate as support and the beads were treated with Al(3+) to
      improve their mechanical strength. Xylose was converted to xylitol using glucose
      as cosubstrate for regeneration of NAD(P)H required in xylitol formation and for
      generation of maintenance energy. The stability of the recombinant strains after
      15 days of continuous operation was evaluated by XR activity and plasmid
      retention analyses. Under anaerobic conditions the volumetric xylitol
      productivity increased with decreasing HRT with both strains. With a recycling
      ratio of 10, volumetric productivities as high as 3.44 and 5.80 g/L . h were
      obtained with the low XR strain at HRT 1.3 h and with the high XR strain at HRT
      2.6 h, respectively. However, the highest overall xylitol yields on xylose and on
      cosubstrate were reached at higher HRTs. Lowering the xylose/cosubstrate ratio
      from 1 to 0.5 increased the overall yield of xylitol on xylose, but the
      productivity and the xylitol yield on cosubstrate decreased. Under oxygen limited
      conditions the effect of the recycling ratio on production parameters was masked
      by other factors, such as an accumulation of free cells in the bioreactor and
      severe genetic instability of the high XR strain. Under anaerobic conditions the
      instability was less severe, causing a decrease in XR activity from 0.15 to 0.10
      and from 3.18 to 1.49 U/mg with the low and high XR strains, respectively. At the
      end of the fermentation, the fraction of plasmid bearing cells in the beads was
      close to 100% for the low XR strain; however, it was significantly lower for the
      high XR strain, particularly for cells from the interior of the beads.

PMID- 18624365
TI  - Immobilization of Candida rugosa lipase to nylon fibers using its carbohydrate
      groups as the chemical link.
AB  - The aim of this study was to evaluate the immobilization of lipase from Candida
      rugosa on a nylon support by methods used to attach biomolecules to solid
      supports through their carbohydrate moieties. The carbohydrate groups were
      converted to dialdehydes by treatment with sodium periodate. The length of
      exposure and the periodate amount were optimized to the point where almost total
      activity retention was obtained. Tests of the immobilized enzyme showed the
      expressed activity to be significantly higher than the activity obtained with the
      unimmobilized enzyme. The use of reverse micelles as a way of delivering water to
      the enzyme was tested and found to give significantly higher activities. The
      immobilized enzyme activity was also tested with other substrates, one of which
      was a chiral ester. The immobilized enzyme was found to have high stereoselective
      efficiency and activity toward racemic methyl methoxyphenyl glycidate, a chiral
      intermediate used in the manufacture of the drug diltiazem.

PMID- 18624366
TI  - Modulation of metabolism of Clostridium acetobutylicum grown in chemostat culture
      in a three-electrode potentiostatic system with methyl viologen as electron
      carrier.
AB  - The metabolism of Clostridium acetobutylicum was manipulated in chemostat culture
      at pH 5 and 6.5 in a three-electrode potentiostatic system with methyl viologen
      (MV) as the electron carrier. When a constant potential was applied at pH 5, the
      broth redox potential continuously decreased and, simultaneously, a high increase
      in the reduced MV concentration (MV(+.)) and the specific rate of butanol
      production was observed while butyric acid was taken up. A linear relationship
      was reported between the specific rate of NAD(P)(+) reduction by ferredoxin
      NAD(P)(+) reductase and the broth redox potential, as long as the growth rate was
      not affected. To reach a steady state in glucose limited culture, a control
      system of the redox potential was required. However, it seems that C.
      acetobutylicum is able to adapt its metabolism when the broth redox potential was
      regulated at low value. On the other hand, at pH 6.5, the current generated by
      the electrochemical device had no effect either on broth redox potential and
      MV(+.) concentration or on the metabolism.

PMID- 18624367
TI  - Optimization of trichloroethylene degradation using soluble methane monooxygenase
      of Methylosinus trichosporium OB3b expressed in recombinant bacteria.
AB  - By complementing cell-free extracts of Pseudomonas putida F1/pSMMO20 with
      purified soluble methane monooxygenase (sMMO) components of Methylosinus
      trichosporium OB3b, the low cloned-gene sMMO activity in the recombinant strain
      was found to be due to incomplete activity of the hydroxylase component. To
      address this incomplete activity, additional sMMO-expressing strains were formed
      by transferring mmo-containing pSMMO20 and pSMMO50 into various bacterial species
      including pseudomonads and alpha-2 subdivision strains such as methanotrophs,
      methylotrophs, Agrobacterium tumefaciens A114, and Rhizobium meliloti 102F34 (11
      new strains screened); sMMO activity was detected in the last two strains. To
      increase plasmid segregational stability, the hok/sok locus originally from
      Escherichia coli plasmid R1 was inserted downstream of the mmo locus of pSMMO20
      (resulting in pSMMO40) and found to enhance plasmid stability in P. putida F1 and
      R. meliloti 102F34 (first report of hok/sok in Rhizobium). To further increase
      sMMO activity, a modified Whittenbury minimal medium was selected from various
      minimal and complex media based on trichloroethylene (TCE) degradation and growth
      rates and was improved by removing the sMMO-inhibiting metal ions [Cu(II),
      Ni(II), and Zn(II)] and chloramphenicol from the medium and by supplementing with
      an iron source (3.6 microM of ferrous ammonium sulfate). Using chemostat-grown P.
      putida F1/pSMMO40, it was found that sMMO activity was higher for cells grown at
      higher dilution rates. These optimization efforts resulted in a twofold increase
      in the extent of TCE degradation and more consistent sMMO activity.

PMID- 18624368
TI  - Activation and regeneration of whole cell biocatalysts: initial and periodic
      induction behavior in starved Escherichia coli after immobilization in thin
      synthetic films.
AB  - Activation and regeneration of whole cell biocatalytic activity via initial and
      subsequent induction of the lacZ gene was investigated in starved Escherichia
      coli using a novel synthetic biofilm. Stationary-phase bacteria were entrapped in
      10-80 mum thick multi-layer films, where a copolymer of acrylic and vinyl acetate
      was the immobilization matrix. The E. coli were placed in a defined starvation
      medium containing essentially no nitrogen or carbon source and induced initially
      using lactose or isopropylthiogalactoside (IPTG). Subsequent inductions were
      performed with IPTG. Comparison studies with suspended bacteria showed that when
      IPTG was the initial inducing agent, induction kinetics are linear for both
      immobilized and suspended cells. After induction with lactose, however, a lag
      time is noted for suspended cells, but not for E. coli in the biofilm.
      Biocatalytic activity was successfully regenerated by re-inducing starved
      suspended cells 1-3 days after an initial induction with lactose. This
      regeneration was demonstrated in the synthesis of additional active beta
      galactosidase. However, immobilized cells could be re-induced for at least 17
      days after the initial induction, and viability in the synthetic biofilms
      remained greater than 90%, demonstrating that periodic induction is a valuable
      method for extending the life of whole cell biocatalysts.

PMID- 18624369
TI  - Optimized enzymatic synthesis of geranyl butyrate with lipase AY from Candida
      rugosa.
AB  - Response surface methodology (RSM) and five-level, five-variable central
      composite rotatable design (CCRD) were used to evaluate the effects of synthetic
      variables, such as reaction time (1-9 h), temperature (25-65 degrees C), enzyme
      amount (10-50%), substrate molar ratio of geraniol to tributyrin (1:0.33-1:1),
      and added water amount (0-20%) on molar percent yield of geranyl butyrate, using
      lipase AY from Candida rugosa. Reaction time and temperature were the most
      important variables and substrate molar ratio had no effect on percent molar
      conversion. Based on contour plots, optimum conditions were: reaction time 9 h,
      temperature 35 degrees C, enzyme amount 50%, substrate molar ratio 1:0.33, and
      added water 10%. The predicted value was 100% and actual experimental value was
      96.8% molar conversion. (c) 1996 John Wiley & Sons, Inc.

PMID- 18624370
TI  - Evidence-based medicine targets the individual patient. Part 2: Guides and tools
      for individual decision-making.

PMID- 18624371
TI  - Adjustable gastric banding improved glycemic control in obese patients with type
      2 diabetes.

PMID- 18624372
TI  - A personal-contact weight-loss maintenance intervention reduced weight regain in
      overweight and obese adults.

PMID- 18624373
TI  - Telling smokers their "lung age" promoted successful smoking cessation.

PMID- 18624374
TI  - Review: late percutaneous coronary intervention after AMI improves survival more
      than optimal medical therapy.

PMID- 18624375
TI  - Review: statins prevent stroke and reduce mortality.

PMID- 18624376
TI  - Review: low-molecular-weight heparin is better than unfractionated heparin to
      prevent VTE after ischemic stroke.

PMID- 18624377
TI  - Review: screening or case-finding questionnaires used alone are not effective in
      the management of depression.

PMID- 18624378
TI  - Daily use of a Lactobacilli probiotic prevented antibiotic-associated diarrhea in
      hospitalized patients.

PMID- 18624379
TI  - Ventilation-perfusion scintigraphy provided useful information for diagnosing
      pulmonary embolism.

PMID- 18624380
TI  - Review: Imaging techniques have similarly high accuracy for diagnosing cancer in
      solitary pulmonary nodules.

PMID- 18624381
TI  - Age, sex, and functional impairment predicted risk for mortality in incident
      dementia at 14 years.

PMID- 18624382
TI  - Young women's risk for first HPV infection was high and increased when the first
      male partner was sexually experienced.

PMID- 18624383
TI  - Correlated piezoelectric and electrical properties in individual ZnO nanorods.
AB  - Resistivity and piezoelectric response of individual ZnO nanorods were measured
      using scanning force microscopy. We found a variation in resistivity of 3 orders
      of magnitude, from 0.1 to 155 Omegacm and in piezoelectric coefficient ranging
      from 0.4 to 9.5 pm/V in ZnO nanorods grown from solution at the same time on the
      same substrate. However, there exists a clear correlation between these two
      properties: nanorods with low piezoelectric response display low resistivity. The
      relationship is explained by the reduction of the Madelung constant due to free
      electrons. The results highlight that slight differences in the local environment
      during synthesis can cause large variation in physical properties found among
      similar nanostructures. These variations cannot be revealed through ensemble
      measurements and may contribute to the confusion in the literature of individual
      nanostructure properties. We demonstrate that correlating multiple physical
      properties on individual nanostructures provides an insight into the origin of
      the varying physical properties.

PMID- 18624384
TI  - Enhanced thermoelectric figure-of-merit in p-type nanostructured bismuth antimony
      tellurium alloys made from elemental chunks.
AB  - By ball milling alloyed bulk crystalline ingots into nanopowders and hot pressing
      them, we had demonstrated high figure-of-merit in nanostructured bulk bismuth
      antimony telluride. In this study, we use the same ball milling and hot press
      technique, but start with elemental chunks of bismuth, antimony, and tellurium to
      avoid the ingot formation step. We show that a peak ZT of about 1.3 in the
      temperature range of 75 and 100 degrees C has been achieved. This process is more
      economical and environmentally friendly than starting from alloyed bulk
      crystalline ingots. The ZT improvement is caused mostly by the lower thermal
      conductivity, similar as the case using ingot. Transmission electron microscopy
      observations of the microstructures suggest that the lower thermal conductivity
      is mainly due to the increased phonon scattering from the increased grain
      boundaries of the nanograins, precipitates, nanodots, and defects. Our material
      also exhibits a ZT of 0.7 at 250 degrees C, similar to the value obtained when
      ingot was used. This study demonstrates that high ZT values can be achieved in
      nanostructured bulk materials with ball milling elemental chunks, suggesting that
      the approach can be applied to other materials that are hard to be made into
      ingot, in addition to its advantage of lower manufacturing cost.

PMID- 18624385
TI  - Magnetic boron nitride nanoribbons with tunable electronic properties.
AB  - We present theoretical evidence, based on total-energy first-principles
      calculations, of the existence of spin-polarized states well localized at and
      extended along the edges of bare zigzag boron nitride nanoribbons. Our
      calculations predict that all the magnetic configurations studied in this work
      are thermally accessible at room temperature and present an energy gap. In
      particular, we show that the high spin state, with a magnetic moment of 1 muB at
      each edge atom, presents a rich spectrum of electronic behaviors as it can be
      controlled by applying an external electric field in order to obtain metallic <-
      > semiconducting <--> half-metallic transitions.

PMID- 18624386
TI  - Cellular uptake and cytotoxicity of silica nanotubes.
AB  - "Template synthesized" silica nanotubes (SNTs) provide unique features such as
      end functionalization to control drug release, inner voids for loading
      biomolecules, and distinctive inner and outer surfaces that can be differentially
      functionalized for targeting and biocompatibility. Very limited information is
      available about their biological interactions. This work evaluates the influence
      of size and surface charge of SNTs on cellular toxicity and uptake. Results
      additionally indicate endocytosis to be one possible mechanism of internalization
      of SNTs.

PMID- 18624387
TI  - Carbon nanotubes and mesenchymal stem cells: biocompatibility, proliferation and
      differentiation.
AB  - The synergy of the unique properties of carbon nanotubes (CNT) with the
      remarkable potential of human mesenchymal stem cells (hMSC) provides an exciting
      opportunity for novel therapeutic modalities. However, little is known about the
      impact of CNT on hMSC behavior. We report the effect of CNT on hMSC renewal,
      metabolic activity, and differentiation. Furthermore, we tracked the
      intracellular movement of CNT through the cytoplasm to a nuclear location and
      assessed effects on cellular ultra structure.

PMID- 18624388
TI  - p-Type ZnO nanowire arrays.
AB  - Well-aligned ZnO nanowire (NW) arrays with durable and reproducible p-type
      conductivity were synthesized on alpha-sapphire substrates by using N2O as a
      dopant source via vapor-liquid-solid growth. The nitrogen-doped ZnO NWs are
      single-crystalline and grown predominantly along the [110] direction, in contrast
      to the [001] direction of undoped ZnO NWs. Electrical transport measurements
      reveal that the nondoped ZnO NWs exhibit n-type conductivity, whereas the
      nitrogen-doped ZnO NWs show compensated highly resistive n-type and finally p
      type conductivity upon increasing N2O ratio in the reaction atmosphere. The
      electrical properties of p-type ZnO NWs are stable and reproducible with a hole
      concentration of (1-2) x 10(18) cm(-3) and a field-effect mobility of 10-17 cm2
      V(-2) s(-1). Surface adsorptions have a significant effect on the transport
      properties of NWs. Temperature-dependent PL spectra of N-doped ZnO NWs show
      acceptor-bound-exciton emission, which corroborates the p-type conductivity. The
      realization of p-type ZnO NWs with durable and controlled transport properties is
      important for fabrication of nanoscale electronic and optoelectronic devices.

PMID- 18624389
TI  - Improved biocompatibility and pharmacokinetics of silica nanoparticles by means
      of a lipid coating: a multimodality investigation.
AB  - Silica is a promising carrier material for nanoparticle-facilitated drug
      delivery, gene therapy, and molecular imaging. Understanding of their
      pharmacokinetics is important to resolve bioapplicability issues. Here we report
      an extensive study on bare and lipid-coated silica nanoparticles in mice. Results
      obtained by use of a wide variety of techniques (fluorescence imaging,
      inductively coupled plasma mass spectrometry, magnetic resonance imaging,
      confocal laser scanning microscopy, and transmission electron microscopy) showed
      that the lipid coating, which enables straightforward functionalization and
      introduction of multiple properties, increases bioapplicability and improves
      pharmacokinetics.

PMID- 18624390
TI  - Synthesis of PbTe nanowire arrays using lithographically patterned nanowire
      electrodeposition.
AB  - We describe the preparation by electrodeposition of arrays of lead telluride
      (PbTe) nanowires using the lithographically patterned nanowire electrodeposition
      (LPNE) method. PbTe nanowires had a rectangular cross-section with adjustable
      width and height ranging between 60-400 nm (w) and 20-100 nm (h). The
      characterization of these nanowire arrays using X-ray diffraction, transmission
      electron microscopy and electron diffraction, scanning electron microscopy,
      atomic force microscopy, and X-ray photoelectron spectroscopy (XPS) is reported.
      PbTe nanowires were electrodeposited using a cyclic electrodeposition-stripping
      technique that produced polycrystalline, stoichiometric, face-centered cubic PbTe
      with a mean grain diameter of 10-20 nm. These nanowires were more than 1 mm in
      length and two additional processing steps permitted their suspension across 25
      microm air gaps microfabricated on these surfaces. The LPNE synthesis of
      lithographically patterned PbTe nanowires was carried out in unfiltered
      laboratory air. Nanowires with lengths of 70-100 microm showed an electrical
      resistivity comparable to bulk PbTe. XPS reveals that exposure of PbTe nanowires
      to air causes the formation on the nanowire surface of approximately one
      monolayer of a mixed lead oxide and tellurium oxide within a few minutes.

PMID- 18624391
TI  - Burning match oxidation process of silicon nanowires screened at the atomic
      scale.
AB  - Silicon oxide nanowires hold great promise for functional nanoscale electronics.
      Here, we investigate the oxidation of straight, massively parallel, metallic Si
      nanowires. We show that the oxidation process starts at the Si NW terminations
      and develops like a burning match. While the spectroscopic signatures on the
      virgin, metallic part, are unaltered we identify four new oxidation states on the
      oxidized part, which show a gap opening, thus revealing the formation of a
      transverse internal nanojunction.

PMID- 18624392
TI  - Pressure-induced orientation control of the growth of epitaxial silicon
      nanowires.
AB  - Single crystal silicon nanowires (SiNWs) were synthesized with silane reactant
      using Au nanocluster-catalyzed one-dimensional growth. We have shown that under
      our experimental conditions, SiNWs grown epitaxially on Si(111) via the vapor
      liquid-solid growth mechanism change their growth direction as a function of the
      total pressure. Structural characterization of a large number of samples shows
      that SiNWs synthesized at a total pressure of 3 mbar grow preferentially in the
      111 direction, while the one at 15 mbar favors the 112 direction. Specifically by
      dynamically changing the system pressure during the growth process morphological
      changes of the NW growth directions along their length have been demonstrated.

PMID- 18624393
TI  - Polarization dependence of surface-enhanced Raman scattering in gold nanoparticle
      nanowire systems.
AB  - We study the polarization dependence of surface-enhanced Raman scattering (SERS)
      in coupled gold nanoparticle-nanowire systems. The coupling between the
      continuous nanowire plasmons and the localized nanoparticle plasmons results in
      significant field enhancements and SERS enhancements comparable to those found in
      nanoparticle dimer junctions. The SERS intensity is maximal when the incident
      light is polarized across the particle and the wire, and the enhancement is
      remarkably insensitive to the detailed geometrical structures of the
      nanoparticles.

PMID- 18624394
TI  - Metallocenyl dendrimers and their applications in molecular electronics, sensing,
      and catalysis.
AB  - We have investigated the movement of electrons around the peripheries of
      dendrimers and between their redox termini and electrodes through studies of the
      electrochemistry of dendrimers presenting metallocenes (and other transition
      metal sandwich complexes) as terminal groups. Because these compounds can be
      stabilized in both their oxidized and their reduced forms, their electrochemical
      and chemical redox processes proceed without decomposition (chemical
      reversibility). Most interestingly, electrochemical studies reveal that electron
      transfer within the dendrimers and between the dendrimers and electrodes are both
      very fast processes when the branches are flexible (electrochemical
      reversibility). When the dendrimer branches are sufficiently long, the redox
      events at the many termini of the metallodendrimer are independent, appearing as
      a single wave in the cyclic voltammogram, because of very weak electrostatic
      effects. As a result, these metallodendrimers have applications in the molecular
      recognition, sensing, and titration of anions (e.g., ATP(2-)) and cations (e.g.,
      transition metal complexes). When the recognition properties are coupled with
      catalysis, the metallodendrimers function in an enzyme-like manner. For example,
      Pd(II) can be recognized and titrated using the dendrimer's terminal redox
      centers and internal coordinate ligands. Redox control over the number of Pd(II)
      species located within a dendrimer allows us to predetermine the number of metal
      atoms that end up in the form of a dendrimer-encapsulated Pd nanoparticle (PdNP).
      For hydrogenation of olefins, the efficiency (turnover frequency, TOF) and
      stability (turnover number, TON) depend on the size of the dendrimer-encapsulated
      PdNP catalysts, similar to the behavior of polymer-supported PdNP catalysts,
      suggesting a classic mechanism in which all of the steps proceed on the PdNP
      surface. On the other hand, Miyaura-Suzuki carbon-carbon bond-forming reactions
      catalyzed by dendrimer-encapsulated PdNPs proceed with TOFs and TONs that do not
      depend on the size of the PdNPs. Moreover these catalysts are more efficient when
      employed in lower (down to "homeopathic") amounts, presumably because of a
      leaching mechanism whereby Pd atoms escape from the PdNP surface subsequent to
      oxidative addition of the aryl halide. Under these conditions, the "mother" PdNPs
      have greater difficulty quenching the extremely active leached Pd atoms because
      of their low concentration. Although dendrimers presenting catalysts at their
      branch termini can be recovered and reused readily, their inner-sphere components
      can lead to steric inhibition of substrate approach. In contrast, star-shaped
      catalysts do not suffer from such steric problems, as has been demonstrated for
      water-soluble dendrimers bearing cationic iron-sandwich termini, which are redox
      catalysts of cathodic nitrate and nitrite reduction in water.

PMID- 18624395
TI  - High affinity conformationally constrained nociceptin/orphanin FQ(1-13) amide
      analogues.
AB  - A series of cyclic analogues with a lactam linkage were prepared by solid phase
      peptide synthesis to explore possible biologically active conformation(s) of
      nociceptin/orphanin FQ (N/OFQ). cyclo[D-Asp(7),Lys(10)]- and cyclo[Asp
      (6),Lys(10)]N/OFQ(1-13)NH2 exhibit high affinity (Ki = 0.27 and 0.34 nM,
      respectively) and high potency in the GTPgammaS assay (EC 50 = 1.6 and 4.1 nM,
      respectively) at human nociceptin/orphanin FQ peptide (NOP) receptors. These
      analogues exhibit 2- to 3-fold higher affinity and 2- to 5-fold higher potency
      than the parent peptide.

PMID- 18624396
TI  - Influence of conformational flexibility on complexation-induced changes in
      chemical shift in a neocarzinostatin protein-ligand complex.
AB  - In this paper is described an analysis of the effects of protein flexibility on
      the observed CIS values and the impact on the accuracy of 3D structures
      determined using a (1)H NMR CIS approach. The effects of protein conformational
      mobility have been investigated by using a set of different protein structures as
      starting points for the calculation: the unbound X-ray crystal structure, the
      unbound NMR solution structure, and the bound NMR solution structure of the
      protein. The results indicated that loop movement does have a significant impact
      on the quality of the structure generated by the CIS structure determination
      methodology. The implementation of methods to treat loop flexibility within our
      protocol, however, did not improve the results for calculations based on the
      unbound protein frame.

PMID- 18624397
TI  - Glycoproteomics of milk: differences in sugar epitopes on human and bovine milk
      fat globule membranes.
AB  - Oligosaccharides from human and bovine milk fat globule membranes were analyzed
      by LC-MS and LC-MS/MS. Global release of N-linked and O-linked oligosaccharides
      showed both to be highly sialylated, with bovine peak-lactating milk O-linked
      oligosaccharides presenting as mono- and disialylated core 1 oligosaccharides
      (Galbeta1-3GalNAcol), while human milk had core type 2 oligosaccharides (Galbeta1
      3(GlcNAcbeta1-6)GalNAcol) with sialylation on the C-3 branch. The C-6 branch of
      these structures was extended with branched and unbranched N-acetyllactosamine
      units terminating in blood group H and Lewis type epitopes. These epitopes were
      also presented on the reducing terminus of the human, but not the bovine, N
      linked oligosaccharides. The O-linked structures were found to be attached to the
      high molecular mass mucins isolated by agarose-polyacrylamide composite gel
      electrophoresis, where MUC1 and MUC4 were present. Analysis of bovine colostrum
      showed that O-linked core 2 oligosaccharides are present at the early stage (3
      days after birth) but are down-regulated as lactation develops. This data
      indicates that human milk may provide different innate immune protection against
      pathogens compared to bovine milk, as evidenced by the presence of Lewis b
      epitope, a target for the Helicobacter pylori bacteria, on human, but not bovine,
      milk fat globule membrane mucins. In addition, non-mucin-type O-linked
      fucosylated oligosaccharides were found (NeuAc-Gal-GlcNAc1-3Fuc-ol in bovine milk
      and Gal-GlcNAc1-3Fuc-ol in human milk). The O-linked fucose structure in human
      milk is the first to our knowledge to be found on high molecular mass mucin-type
      molecules.

PMID- 18624398
TI  - Protein interaction data set highlighted with human Ras-MAPK/PI3K signaling
      pathways.
AB  - The Ras-MAPK and PI3K-AKT pathways are conserved in metazoan organisms, which
      involve a series of signaling cascades and form the basis for numerous
      physiological and pathological processes. Here we report on yeast two hybrid
      screening results of a protein interaction network around the known components of
      human Ras-MAPK/PI3K pathways. A total of 42 independent cDNA library screenings
      resulted in 200 protein-protein interaction (PPI) pairs among 180 molecules. Most
      of the proteins formed a large cluster that contains 193 PPIs between 169
      proteins. Seventy-four interactions indicate high-confidence according to
      bioinformatics analysis. The prey list contains high enrichment genes with
      specific Gene Ontology (GO) terms such as response to stress and response to
      external stimulus. Most interactions link the Ras signaling pathway with various
      cellular processes. Five interactions were validated by coimmunoprecipitation and
      colocalization assays in mammalian cells to confirm their in vivo interactions.
      This protein interaction network provides further insights into the molecular
      mechanism of Ras-MAPK/PI3K signaling pathways.

PMID- 18624399
TI  - A mouse model repository for cancer biomarker discovery.
AB  - Early detection of cancer using biomarkers obtained from blood or other easily
      accessible tissues would have a significant impact on reducing cancer mortality.
      However, identifying new blood-based biomarkers has been hindered by the dynamic
      complexity of the human plasma proteome, confounded by genetic and environmental
      variability, and the scarcity of high quality controlled samples. In this report,
      we discuss a new paradigm for biomarker discovery through the use of mouse
      models. Inbred mouse models of cancer recapitulate many critical features of
      human cancer, while eliminating sources of environmental and genetic variability.
      The ability to collect samples from highly matched cases and controls under
      identical conditions further reduces variability which is critical for successful
      biomarker discovery. We describe the establishment of a repository containing
      tumor, plasma, urine, and other tissues from 10 different mouse models of human
      cancer, including two breast, two lung, two prostate, two gastrointestinal, one
      ovarian, and one skin tumor model. We present the overall design of this resource
      and its potential use by the research community for biomarker discovery.

PMID- 18624400
TI  - Introduction of the disulfide proteome: application of a technique for the
      analysis of plant storage proteins as well as allergens.
AB  - Redox regulation plays an important role across a broad spectrum of biology.
      Accumulating evidence suggests that thioredoxin, a widely distributed redox
      enzyme, participates in the redox control of numerous target proteins, thus,
      playing a key role as a signaling intermediate that senses the metabolic state or
      environmental changes, and transmits information to induce appropriate reactions
      for survival. The recent development of proteomic strategies has facilitated the
      identification of thioredoxin targets to allow clarification of new thioredoxin
      dependent redox mechanisms. This review examines the usefulness of a disulfide
      proteome technique for the analysis of thioredoxin-dependent redox regulation as
      well as for use in allergen studies.

PMID- 18624401
TI  - Solubility challenge: can you predict solubilities of 32 molecules using a
      database of 100 reliable measurements?
AB  - Solubility is a key physicochemical property of molecules. Serious deficiencies
      exist in the consistency and reliability of solubility data in the literature.
      The accurate prediction of solubility would be very useful. However, systematic
      errors and lack of metadata associated with measurements greatly reduce the
      confidence in current models. To address this, we are accurately measuring
      intrinsic solubility values, and here we report results for a diverse set of 100
      druglike molecules at 25 degrees C and an ionic strength of 0.15 M using the
      CheqSol approach. This is a highly reproducible potentiometric technique that
      ensures the thermodynamic equilibrium is reached rapidly. Results with a
      coefficient of variation higher than 4% were rejected. In addition, the
      Potentiometric Cycling for Polymorph Creation method, [PC] (2), was used to
      obtain multiple polymorph forms from aqueous solution. We now challenge
      researchers to predict the intrinsic solubility of 32 other druglike molecules
      that have been measured but are yet to be published.

PMID- 18624402
TI  - [Pt]2Pb trinuclear systems: impact of the anionic platinum fragment on the lead
      environment and photoluminescence.
AB  - A comparison of the solid structures of three novel trinuclear sandwich Pt 2Pb
      systems (NBu 4) 2[{Pt(C identical withCTol) 4} 2Pb(OH 2) 2] 1, [{Pt(bzq)(C
      identical withCPh) 2} 2Pb] 2, and (NBu 4)[{Pt(bzq)(C identical withCC 6H 4-CF 3
      4) 2} 2Pb(O 2ClO 2)] 4 (NBu 4[ 3.(O 2ClO 2)]) with that of the previously
      reported (NBu 4) 2[{Pt(C 6F 5) 4} 2Pb] 5 showed that the local environment of Pb
      (II) is highly sensitive to the nature of the anionic platinate(II) precursors.
      The photoluminescence (PL) studies of all 1- 5 complexes revealed a dependence of
      PL on the structure type. Thus, complexes 1 and 5 exhibit metal centered
      emissions ( 1, 497 nm, 77 K; 5, 539 nm, varphi = 0.43, 298 K) related to the
      linear ( 5) or bent ( 1 Pt-Pb-Pt 149.9 degrees ) trinuclear entities. However, in
      complexes 2- 4, that have unprecedented Pb (II)...eta (1)(C identical withCR)
      bonding interactions and very short Pt...Pb and Pt...Pt distances, the emissive
      state in solid state (77 K) is attributed to a (3)MLM'CT [Pt(1)pi(C identical
      withCR)-->Pt(2)/Pb(sp)pi*(C identical withCR)] state mixed with some pipi*
      excimeric character in neutral complexes 2 (R = Ph) and 3 (R = C 6H 4-CF 3-4),
      and in the case of the adduct (NBu 4)[{Pt(bzq)(C identical withCC 6H 4-CF 3-4) 2}
      2Pb(O 2ClO 2)] 4 modified also by Pb (II)...O (O 2ClO 2 (-)) contacts.

PMID- 18624403
TI  - Molybdenum and tungsten structural differences are dependent on ndz(2)/(n + 1)s
      mixing: comparisons of (silox)3MX/R (M = Mo, W; silox = (t)Bu3SiO).
AB  - Treatment of trans-(Et 2O) 2MoCl 4 with 2 or 3 equiv of Na(silox) (i.e., NaOSi
      (t) Bu 3) afforded (silox) 3MoCl 2 ( 1-Mo) or (silox) 3MoCl ( 2-Mo). Purification
      of 2-Mo was accomplished via addition of PMe 3 to precipitate (silox) 3ClMoPMe 3
      ( 2-MoPMe 3), followed by thermolysis to remove phosphine. Use of MoCl 3(THF) 3
      with various amounts of Na(silox) produced (silox) 2ClMoMoCl(silox) 2 ( 3-Mo).
      Alkylation of 2-Mo with MeMgBr or EtMgBr afforded (silox) 3MoR (R = Me, 2-MoMe;
      Et, 2-MoEt). 2-MoEt was also synthesized from C 2H 4 and (silox) 3MoH, which was
      prepared from 2-Mo and NaBEt 3H. Thermolysis of WCl 6 with HOSi ( t )Bu 3
      afforded (silox) 2WCl 4 ( 4-W), and sequential treatment of 4-W with Na/Hg and
      Na(silox) provided (silox) 3WCl 2 ( 1-W, tbp, X-ray), which was alternatively
      prepared from trans-(Et 2S) 2WCl 4 and 3 equiv of Tl(silox). Na/Hg reduction of 1
      W generated (silox) 3WCl ( 2-W). Alkylation of 2-W with MeMgBr produced (silox)
      3WMe ( 2-WMe), which dehydrogenated to (silox) 3WCH ( 6-W) with Delta H (double
      dagger) = 14.9(9) kcal/mol and Delta S (double dagger) = -26(2) eu. Magnetism and
      structural studies revealed that 2-Mo and 2-MoEt have triplet ground states (GS)
      and distorted trigonal monopyramid (tmp) and tmp structures, respectively. In
      contrast, 2-W and 2-WMe possess squashed-T d (distorted square planar)
      structures, and the former has a singlet GS. Quantum mechanics/molecular
      mechanics studies of the S = 0 and S = 1 states for full models of 2-Mo, 2-MoEt,
      2-W, and 2-WMe corroborate the experimental findings and are consistent with the
      greater nd z (2) /( n + 1)s mixing in the third-row transition-metal species
      being the dominant feature in determining the structural disparity between
      molybdenum and tungsten.

PMID- 18624404
TI  - Catechol oxidase activity of a series of new dinuclear copper(II) complexes with
      3,5-DTBC and TCC as substrates: syntheses, X-ray crystal structures,
      spectroscopic characterization of the adducts and kinetic studies.
AB  - A series of dinuclear copper(II) complexes has been synthesized with the aim to
      investigate their applicability as potential structure and function models for
      the active site of catechol oxidase enzyme. They have been characterized by
      routine physicochemical techniques as well as by X-ray single-crystal structure
      analysis: [Cu 2(H 2L2 (2))(OH)(H 2O)(NO 3)](NO 3) 3.2H 2O ( 1), [Cu(HL1 (4))(H
      2O)(NO 3)] 2(NO 3) 2.2H 2O ( 2), [Cu(L1 (1))(H 2O)(NO 3)] 2 ( 3), [Cu 2(L2
      (3))(OH)(H 2O) 2](NO 3) 2, ( 4) and [Cu 2(L2 (1))(N 3) 3] ( 5) [L1 = 2-formyl-4
      methyl-6R-iminomethyl-phenolato and L2 = 2,6-bis(R-iminomethyl)-4-methyl
      phenolato; for L1 (1) and L2 (1), R = N-propylmorpholine; for L2 (2), R = N
      ethylpiperazine; for L2 (3), R = N-ethylpyrrolidine, and for L1 (4), R = N
      ethylmorpholine]. Dinuclear 1 and 4 possess two "end-off" compartmental ligands
      with exogenous mu-hydroxido and endogenous mu-phenoxido groups leading to
      intermetallic distances of 2.9794(15) and 2.9435(9) A, respectively; 2 and 3 are
      formed by two tridentate compartmental ligands where the copper centers are
      connected by endogenous phenoxido bridges with Cu-Cu separations of 3.0213(13)
      and 3.0152(15) A, respectively; 5 is built by an end-off compartmental ligand
      having exogenous mu-azido and endogenous mu-phenoxido groups with a Cu-Cu
      distance of 3.133(2) A (mean of two independent molecules). The catecholase
      activity of all of the complexes has been investigated in acetonitrile and
      methanol medium by UV-vis spectrophotometric study using 3,5-di- tert
      butylcatechol (3,5-DTBC) and tetrachlorocatechol (TCC) as substrates. In
      acetonitrile medium, the conversion of 3,5-DTBC to 3,5-di- tert-butylbenzoquinone
      (3,5-DTBQ) catalyzed by 1- 5 is observed to proceed via the formation of two
      enzyme-substrate adducts, ES1 and ES2, detected spectroscopically for the first
      time. In methanol medium no such enzyme-substrate adduct has been detected, and
      the 3,5-DTBC to 3,5-DTBQ conversion is observed to be catalyzed by 1- 5 very
      efficiently. The substrate TCC forms an adduct with 2- 5 without performing
      further oxidation to TCQ due to the high reduction potential of TCC (in
      comparison with 3,5-DTBC). But most interestingly, 1 is observed to be effective
      even in TCC oxidation, a process never reported earlier. Kinetic experiments have
      been performed to determine initial rate of reactions (3,5-DTBC as substrate, in
      methanol medium) and the activity sequence is 1 > 5 > 2 = 4 > 3. A treatment on
      the basis of Michaelis-Menten model has been applied for kinetic study,
      suggesting that all five complexes exhibit very high turnover number, especially
      1, which exhibits turnover number or K cat of 3.24 x 10 (4) (h (-1)), which is
      approximately 3.5 times higher than the most efficient catalyst reported to date
      for catecholase activity in methanol medium.

PMID- 18624405
TI  - Characterization and application of controllable local chemical changes produced
      by reagent delivery from a nanopipet.
AB  - We introduce a versatile method that allows local and repeatable delivery (or
      depletion) of any water-soluble reagent from a nanopipet in ionic solution to
      make localized controlled changes in reagent concentration at a surface. In this
      work, Na(+) or OH(-) ions were dosed from the pipet using pulsed voltage-driven
      delivery. Total internal reflection fluorescence from CoroNa Green dye in the
      bath for Na(+) ions or fluorescein in the bath for pH quantified the resulting
      changes in local surface concentration. These changes had a time response as
      short as 10 ms and a radius of 1-30 microm and depended on the diameter of the
      pipet used, the applied voltage, and the pipet-surface separation. After the
      pipet dosing was characterized in detail, two proof-of-concept experiments on
      single cells and single molecules were then performed. We demonstrated local
      control of the sodium-sensitive flagellar motor in single Escherichia coli
      chimera on the time scale of 1 s by dosing sodium and monitoring the rotation of
      a 1 microm diameter bead fixed to the flagellum. We also demonstrated triggered
      single-molecule unfolding by dosing acid from the pipet to locally melt
      individual molecules of duplex DNA, as observed using fluorescent resonance
      energy transfer.

PMID- 18624406
TI  - Thermal signature of hydrophobic hydration dynamics.
AB  - Hydrophobic hydration, the perturbation of the aqueous solvent near an apolar
      solute or interface, is a fundamental ingredient in many chemical and biological
      processes. Both bulk water and aqueous solutions of apolar solutes behave
      anomalously at low temperatures for reasons that are not fully understood. Here,
      we use (2)H NMR relaxation to characterize the rotational dynamics in hydrophobic
      hydration shells over a wide temperature range, extending down to 243 K. We
      examine four partly hydrophobic solutes: the peptides N-acetyl-glycine-N'
      methylamide and N-acetyl-leucine-N'-methylamide, and the osmolytes trimethylamine
      N-oxide and tetramethylurea. For all four solutes, we find that water rotates
      with lower activation energy in the hydration shell than in bulk water below 255
      +/- 2 K. At still lower temperatures, water rotation is predicted to be faster in
      the shell than in bulk. We rationalize this behavior in terms of the geometric
      constraints imposed by the solute. These findings reverse the classical "iceberg"
      view of hydrophobic hydration by indicating that hydrophobic hydration water is
      less ice-like than bulk water. Our results also challenge the "structural
      temperature" concept. The two investigated osmolytes have opposite effects on
      protein stability but have virtually the same effect on water dynamics,
      suggesting that they do not act indirectly via solvent perturbations. The NMR
      derived picture of hydrophobic hydration dynamics differs substantially from
      views emerging from recent quasielastic neutron scattering and pump-probe
      infrared spectroscopy studies of the same solutes. We discuss the possible
      reasons for these discrepancies.

PMID- 18624408
TI  - Self-assembly and cross-linking of FePt nanoparticles at planar and colloidal
      liquid-liquid interfaces.
AB  - Terpyridine thiol functionalized FePt and Au NPs were self-assembled and cross
      linked at the liquid-liquid interfaces using Fe(II) metal ion. Complexation of
      terpyridine with Fe(II) metal ion leads to NP network and affords stable
      membranes and colloidal shells at the liquid-liquid interfaces.

PMID- 18624407
TI  - Stimuli-responsive polyguanidino-oxanorbornene membrane transporters as
      multicomponent sensors in complex matrices.
AB  - We introduce guanidinium-containing synthetic polymers based on polyguanidino
      oxanorbornenes (PGONs) as anion transporters in lipid bilayers that can be
      activated and inactivated by chemical stimulation. According to fluorogenic anion
      export experiments with vesicles, PGON transporters are most active in neutral
      bilayers near their phase transition, with EC50's in the nanomolar range. Six
      times higher effective transporter concentrations were measured with
      aminonaphthalene-1,3,6-trisulfonate than with 5(6)-carboxyfluorescein,
      demonstrating the importance of anion binding for transport and excluding
      nonspecific efflux. Negative surface potentials efficiently annihilate transport
      activity, while inside-negative membrane potentials slightly increase it. These
      trends demonstrate the functional importance of counterions to hinder the binding
      of hydrophilic counterions and to minimize the global positive charge of the
      transporter-counterion complexes. Strong, nonlinear increases in activity with
      polymer length reveal a significant polymer effect. Overall, the characteristics
      of PGONs do not match those of similar systems (for example, polyarginine) and
      hint toward an interesting mode of action, clearly different from nonspecific
      leakage caused by detergents. The activity of PGONs increases in the presence of
      amphiphilic anions such as pyrenebutyrate (EC50 = 70 microM), while several other
      amphiphilic anions tested were inactive. PGONs are efficiently inactivated by
      numerous hydrophilic anions including ATP (IC 50 = 150 microM), ADP (IC50 = 460
      microM), heparin (IC50 = 1.0 microM), phytate (IC50 = 0.4 microM), and CB
      hydrazide (IC50 = 26 microM). The compatibility of this broad responsiveness with
      multicomponent sensing in complex matrices is discussed and illustrated with
      lactate sensing in sour milk. The PGON lactate sensor operates together with
      lactate oxidase as a specific signal generator and CB hydrazide as an amplifier
      for covalent capture of the pyruvate product as CB hydrazone (IC50 = 1.5 microM).

PMID- 18624409
TI  - Multivariate modeling of aging in bottled lager beer by principal component
      analysis and multiple regression methods.
AB  - Data collected from the sensory test score evaluation of bottled lager beer,
      together with the chemical components related to aging, including carbonyl
      compounds, higher alcohols, unsaturated fatty acid, organic acids, alpha-amino
      acids, dissolved oxygen, and staling evaluation indices, including lag time of
      electron spin resonance (ESR) curve, 1,1'-diphenyl-2-picrylhydrazyl (DPPH)
      scavenged amounts, and thiobarbituric acid (TBA) values, were used to predict the
      extent of aging in bottled lager beer, using both multiple linear regression and
      principal component analysis methods. Carbonyl compounds, higher alcohols, and
      TBA value were significantly and positively correlated with sensory evaluation of
      staling flavor. While lag time and DPPH scavenging amount were negatively
      correlated with taste test score. Multiple regression analysis was used to fit
      the sensory test data using the above chemical compound aging related parameters
      and evaluation indices as predictors. A variable selection method based on high
      loadings of varimax rotated principal components was used to obtain subsets of
      the predominant predictor variables to be included in the regression model of
      beer aging, so as to eliminate the multicollinearity of the original nine
      variables. It was found that staling extent was influenced significantly by
      higher alcohols, TBA value, and DPPH scavenging amount, and the multicollinearity
      of the regression model was found to be weak by examining the variance inflation
      factors of the new predictor variables. A mathematic model of the organoleptic
      test score for beer aging using these three predictors was obtained by multiple
      linear regression, showing that the major contributors to the sensory taste of
      beer aging were higher alcohols, TBA index, and DPPH scavenging amount, with the
      adjusted R(2) of the model being 0.62.

PMID- 18624410
TI  - Characterization and quantification of grape variety by means of shikimic acid
      concentration and protein fingerprint in still white wines.
AB  - Protein profiles, obtained by high-performance capillary electrophoresis (HPCE)
      on white wines previously dialyzed, combined with shikimic acid concentration and
      multivariate analysis, were used for the determination of grape variety
      composition of a still white wine. Six varieties were studied through
      monovarietal wines elaborated in the laboratory: Chardonnay (24 samples), Chenin
      (24), Petit Manseng (7), Sauvignon (37), Semillon (24), and Ugni Blanc (9).
      Homemade mixtures were elaborated from authentic monovarietal wines according to
      a Plackett-Burman sampling plan. After protein peak area normalization, a matrix
      was elaborated containing protein results of wines (mixtures and monovarietal).
      Partial least-squares processing was applied to this matrix allowing the
      elaboration of a model that provided a varietal quantification precision of
      around 20% for most of the grape varieties studied. The model was applied to
      commercial samples from various geographical origins, providing encouraging
      results for control purposes.

PMID- 18624411
TI  - Antioxidant effectiveness of phenolic apple juice extracts and their gut
      fermentation products in the human colon carcinoma cell line caco-2.
AB  - Apples represent a major dietary source of antioxidative polyphenols. Their
      metabolic conversion by the gut microflora might generate products that protect
      the intestine against oxidative damage. We studied the antioxidant effectiveness
      of supernatants of fermented apple juice extracts (F-AEs, 6 and 24 h
      fermentation) and of selected phenolic degradation products, identified by HPLC
      DAD-ESI-MS. Cell free antioxidant capacity of unfermented apple juice extracts
      (AEs) was decreased after fermentation by 30-50%. In the human colon carcinoma
      cell line Caco-2, F-AEs (containing <0.5% of original AE-phenolics) decreased the
      reactive oxygen species (ROS) level more efficiently than the F-blank (fermented
      without AE) but were less effective than the respective AEs. Similarly,
      antioxidant effectiveness of individual degradation products was lower compared
      to respective AE constituents. Glutathione level was slightly increased and
      oxidative DNA damage slightly decreased by fermented AE03, rich in quercetin
      glycosides. In conclusion, F-AEs/degradation products exhibit antioxidant
      activity in colon cells but to a lesser extent than the respective unfermented
      AEs/constituents.

PMID- 18624412
TI  - Kinetics of freshly squeezed orange juice quality changes during ozone
      processing.
AB  - Freshly squeezed orange juice samples were ozonated with control variables of gas
      flow rate (0-0.25 L min (-1)), ozone concentration (0.6-10.0%w/w), and treatment
      time (0-10 min). Effects of ozone processing variables on orange juice quality
      parameters of pH, degrees Brix, titratable acidity (TA), cloud value,
      nonenzymatic browning (NEB), color values ( L*, a*, and b*), and ascorbic acid
      content were determined. No significant changes in pH, degrees Brix, TA, cloud
      value, and NEB ( p < 0.05) were found. L*, a*, and b* color values were
      significantly affected by gas flow rate, ozone concentration, and treatment time.
      The changes in lightness ( L*) values and total color difference (TCD) values
      were fitted well to zero-order kinetics, whereas a*, b*, and ascorbic acid
      degradation followed first-order kinetics. The rate constants for a*, b*, and TCD
      were linearly correlated with ozone concentration ( R (2) = 0.88-0.99), whereas
      the rate constants for L* and ascorbic acid were exponentially correlated ( R (2)
      = 0.94-0.98).

PMID- 18624413
TI  - Uptake of SigmaDDT, arsenic, cadmium, copper, and lead by lettuce and radish
      grown in contaminated horticultural soils.
AB  - Horticultural soils can contain elevated concentrations of selected trace
      elements and organochlorine pesticides as a result of long-term use of
      agrichemicals and soil amendments. A glasshouse study was undertaken to assess
      the uptake of weathered SigmaDDT {sum of the p, p'- and o, p-isomers of DDT
      [1,1,1-trichloro-2,2- bis( p-chlorophenyl)ethane], DDE [1,1-dichloro-2,2- bis( p
      chlorophenyl)ethylene] and DDD[1,1-dichloro-2,2- bis( p-chlorophenyl)ethane]},
      arsenic (As), cadmium (Cd), copper (Cu), and lead (Pb) residues by lettuce (
      Lactuca sativa) and radish ( Raphanus sativus) from field-aged New Zealand
      horticultural soils. Concentrations of SigmaDDT, DDT, DDE, Cd, Cu, and Pb in
      lettuce increased with increasing soil concentrations. In radish, similar
      relationships were observed for SigmaDDT, DDE, and Cu. The bioaccumulation
      factors were less than 1 with the exception of Cd and decreased with increasing
      soil concentrations. Lettuce Cd concentrations for plants grown on four out of 10
      assayed soils were equivalent to or exceeded the New Zealand food standard for
      leafy vegetables of 0.1 mg kg (-1) fresh weight. Concentrations of As, Pb, and
      SigmaDDT did not exceed available food standards. Overall, these results
      demonstrate that aged residues of SigmaDDT, As, Cd, Cu, and Pb in horticultural
      soils have remained phytoavailable. To be protective of human health, site
      specific risk assessments and soil guideline derivations for residential settings
      with vegetable gardens need to consider the produce consumption pathway.

PMID- 18624414
TI  - Ionic liquids/[bmim][N3] mixtures: promising media for the synthesis of aryl
      azides by SNAr.
AB  - The nucleophilic aromatic substitution of some activated aryl or heteroaryl
      halides has been performed in ionic liquid solution, using the 1-butyl-3
      methylimidazolium azide as a nucleophile. The reaction course was studied varying
      the structures of both substrates and ionic liquids. In particular, in the latter
      case, the reaction of 2-bromo-5-nitrothiophene was carried out in five different
      ionic liquids ([bmim][BF 4], [bmim][PF 6], [bmim][NTf 2], [bm 2im][NTf 2], and
      [bmpyrr][NTf 2]). Finally, for all the substrates considered, a comparison with
      data obtained in MeOH solution in the presence of NaN 3 was also performed. Data
      collected indicate that in some cases it is possible to obtain aromatic or
      heteroaromatic azide derivatives in satisfactory yield by means of a S NAr
      reaction using [bmim][N 3] as the nucleophile.

PMID- 18624415
TI  - Redox cycling in the metabolism of the environmental pollutant and suspected
      human carcinogen o-anisidine by rat and rabbit hepatic microsomes.
AB  - We investigated the ability of hepatic microsomes from rat and rabbit to
      metabolize 2-methoxyaniline (o-anisidine), an industrial and environmental
      pollutant and a bladder carcinogen for rodents. Using HPLC combined with
      electrospray tandem mass spectrometry, we determined that o-anisidine is oxidized
      by microsomes of both species to N-(2-methoxyphenyl)hydroxylamine, o-aminophenol,
      and one additional metabolite, the exact structure of which has not been
      identified as yet. N-(2-Methoxyphenyl)hydroxylamine is either further oxidized to
      2-methoxynitrosobenzene (o-nitrosoanisole) or reduced to parental o-anisidine,
      which can be oxidized again to produce o-aminophenol. To define the role of
      microsomal cytochromes P450 (P450) in o-anisidine metabolism, we investigated the
      modulation of this metabolism by specific inducers and selective inhibitors of
      these enzymes. The results of the studies suggest that o-anisidine is a
      promiscuous substrate of P450s of rat and rabbit liver; because P450s of 1A, 2B,
      2E, and 3A subfamilies metabolize o-anisidine in hepatic microsomes of both
      studied species. Using purified enzymes of rat and rabbit (P450s 1A1, 1A2, 2B2,
      2B4, 2E1, 2C3, 3A1, and 3A6), reconstituted with NADPH:P450 reductase, the
      ability of P450s 1A1, 1A2, 2B2, 2B4, 2E1, and 3A6 to metabolize o-anisidine was
      confirmed. In the reconstituted P450 system, rabbit P450 2E1 was the most
      efficient enzyme metabolizing o-anisidine. The data demonstrate the participation
      of different rat and rabbit P450s in o-anisidine metabolism and indicate that
      both experimental animal species might serve as suitable models to mimic the fate
      of o-anisidine in human.

PMID- 18624417
TI  - Surface functionalization and characterization of magnetic polystyrene
      microbeads.
AB  - A new approach to the surface functionalization of magnetic polystyrene
      microbeads with chloroacetyl chloride in the presence of aluminum chloride was
      reported. Composite microbeads consisting of polymer-coated iron oxide
      nanoparticles were prepared by spraying suspension polymerization. Functional
      chloride groups were introduced onto the surface of magnetic polystyrene
      microbeads by surface chemical reaction without destroying the magnetite
      nanoparticles within the microbeads. First, a complex was synthesized by a
      reaction between aluminum chloride and chloroacetyl chloride. Then, the complex
      was added dropwise to the solution of magnetic polystyrene microbeads, and a
      surface acylation reaction between complex and polystyrene microbeads was carried
      out. Subsequently, the amino groups were coupled to the magnetic microbeads via
      an ammonolysis reaction between ethylenediamine and chloride groups on the
      acylated magnetic polystyrene microbeads. The chemical composition, surface
      functional groups, and magnetism of the magnetic polystyrene microbeads before
      and after surface functionalization were characterized by Fourier transform
      infrared spectroscopy and vibrating sample magnetometry. The results showed that
      the surface functionalization reaction had little impact on the magnetism of the
      microbeads. The content of surface amino groups on the magnetic polystyrene
      microbeads was found to be 0.2 mmol/g. An affinity dye, Cibacron Blue F3G-A (CB),
      was then immobilized to prepare a magnetic affinity adsorbent. It was confirmed
      from X-ray photoelectron spectroscopy spectra that the CB molecules were
      covalently coupled on the magnetic microbeads.

PMID- 18624416
TI  - Molecular beacon-metal nanowire interface: effect of probe sequence and surface
      coverage on sensor performance.
AB  - We report the effect of surface coverage and sequence on the performance of 5'
      thiolated, 3' fluorophore-labeled DNA hairpin probes bound to Au/Ag striped
      ("barcoded") metal nanowires. Coverage was controlled by varying probe
      concentration, buffer ionic strength, and by addition of short hydroxy-terminated
      alkanethiol diluent molecules during probe assembly onto the nanowire surface.
      Surface dilution of the surface-bound probes with a omega-hydroxyl alkanethiol, a
      commonly accepted practice in the surface-bound DNA literature, did not
      appreciably improve sensor performance as compared to similar probe coverages
      without hydroxyalkanethiol diluents; this finding underscores the differences
      between the molecular beacon probes used here and more traditional
      nonfluorescent, random coil probes. We found that intermediate probe coverage of
      approximately 10 (12) molecules/cm (2) gave the best discrimination between
      presence and absence of a target sequence. Because we are interested in
      multiplexed assays, we also compared several beacon probe sequences having
      different stabilities for secondary structure formation in solution; we found
      that both probe surface coverage and sensor performance varied for different
      probe sequences. When five different molecular beacon probes, each bound to
      barcoded nanowires, were used in a multiplexed, wash-free assay for target
      oligonucleotides corresponding to viral nucleic acid sequences, these differences
      in probe performance did not prevent accurate target identification. We
      anticipate that the findings described here will also be relevant to other
      applications involving molecular beacons or other structured nucleic acid probes
      immobilized on metal surfaces.

PMID- 18624418
TI  - Optimized preparation and scanning electrochemical microscopy analysis in
      feedback mode of glucose oxidase layers grafted onto conducting carbon surfaces.
AB  - An optimized immobilization procedure based on the electroreduction of
      aryldiazonium salt followed by covalent attachment of a cross-linked hydrogel was
      used to graft glucose oxidase on a carbon surface. Scanning electrochemical
      microscopy (SECM) and cyclic voltammetry were used to follow the construction
      steps of the modified electrode. By adjusting the compactness of the layer
      through the electrografting reaction, the penetration of the mediator through the
      layer can be controlled to allow the monitoring of the enzymatic activity by both
      cyclic voltammetry and SECM in feedback mode. The enzymatic activity of the film
      is finally characterized by SECM.

PMID- 18624419
TI  - Electrochemistry of catechol terminated monolayers with Cu(II), Ni(II) and
      Fe(III) cations: a model for the marine adhesive interface.
AB  - The redox electrochemistry of hydroquinone and Cu2+-, Ni2+-, and Fe3+
      hydroquinone complexes immobilized at the SAM interface has been studied in
      aqueous solutions with pH 5 to 12 using cyclic voltammetry. Self-assembled
      monolayers were constructed with terminal hydroquinone residues designed to model
      marine adhesive proteins that use the DOPA (3,4-dihydroxyphenylalanine) moiety.
      Coordination of metal to the hydroquinone group results in a shift to the ligand
      oxidation potential, with the value for Delta E p,a dependent on the solution pH
      and identity of the metal. Cu2+ shifts the hydroquinone oxidation by -285 mV (pH
      8.8), and Ni2+ by -194 mV (pH 9.16). The hydroquinone oxidation was shifted by 
      440 mV at pH 5 for Fe3+ solutions examined up to pH 7. By contrast, reduction of
      the quinone is unperturbed by the presence of Cu2+, Ni2+, and Fe3+ ions.
      Implications of these results to the mechanism of marine adhesion are discussed.

PMID- 18624420
TI  - Initial oxidation and interfacial diffusion of Zn on faceted MgO(111) films.
AB  - The interaction of zinc and faceted MgO(111) thin films prepared on a Mo(110)
      substrate was investigated in situ by using various surface analysis techniques,
      including X-ray photoelectron spectroscopy, ultraviolet photoelectron
      spectroscopy, Auger electron spectroscopy, high-resolution electron energy loss
      spectroscopy, and low-energy electron diffraction. The results revealed that
      three-dimensional Zn islands exist on the faceted MgO(111) films and that no
      chemical interaction takes place at the interface at room temperature. Initially,
      deposited Zn is stable at temperatures below 400 K and diffuses into MgO at
      temperatures above 425 K. A portion of Zn is oxidized at approximately 10 (-6)
      mbar O 2 at room temperature. An interfacial phase of Zn x Mg 1- x O was formed
      after Zn was exposed to approximately 10 (-6) mbar O 2 at temperatures >or=500 K.
      The faceted structure on the MgO(111) surface is of a disadvantage for the
      epitaxial growth of ZnO films.

PMID- 18624421
TI  - Targeting the lysosome: fluorescent iron(III) chelators to selectively monitor
      endosomal/lysosomal labile iron pools.
AB  - Iron-sensitive fluorescent chemosensors in combination with digital fluorescence
      spectroscopy have led to the identification of a distinct subcellular
      compartmentation of intracellular redox-active "labile" iron. To investigate the
      distribution of labile iron, our research has been focused on the development of
      fluorescent iron sensors targeting the endosomal/lysosomal system. Following the
      recent introduction of a series of 3-hydroxypyridin-4-one (HPO) based fluorescent
      probes we present here two novel HPO sensors capable of accumulating and
      monitoring iron exclusively in endosomal/lysosomal compartments. Flow cytometric
      and confocal microscopy studies in murine macrophages revealed
      endosomal/lysosomal sequestration of the probes and high responsiveness toward
      alterations of vesicular labile iron concentrations. This allowed assessment of
      cellular iron status with high sensitivity in response to the clinically applied
      medications desferrioxamine, deferiprone, and deferasirox. The probes represent a
      powerful class of sensors for quantitative iron detection and clinical real-time
      monitoring of subcellular labile iron levels in health and disease.

PMID- 18624422
TI  - Gamma-cyclodextrin forms a highly compressible complex with 1
      adamantanecarboxylic acid.
AB  - We report temperature-dependent ultrasonic velocimetric and densimetric data on
      changes in volume, expansibility, and adiabatic compressibility associated with
      the binding of 1-adamantanecarboxylic acid (AD) to gamma-cyclodextrin (gamma-CD).
      We compare these results with our previous data on the binding of AD to beta
      cyclodextrin (beta-CD) [Taulier, N.; Chalikian, T.V.J. Phys. Chem. B 2006, 110,
      12222-12224]. The comparison reveals that, in contrast to the tight AD-beta-CD
      complex with little void space left inside the cavity, AD forms a loose complex
      with gamma-CD with approximately 30 A3 of void space between the guest molecule
      and the inner walls of the cavity. The presence of the void renders the AD-gamma
      CD complex highly compressible; the intrinsic coefficient of compressibility of
      the AD-gamma-CD complex is 37x10(-6) bar(-1) at 18 degrees C and decreases to
      23x10(-6) bar(-1) at 55 degrees C. Such large compressibility is suggestive of
      only weak contacts between the interacting AD and gamma-CD atomic groups in the
      cavity. Our results are consistent with the notion that the AD-gamma-CD complex
      is predominantly stabilized by the hydrophobic effect with only modest
      contribution from intermolecular van der Waals interactions. This notion is in
      contrast to the AD-beta-CD complex which is stabilized by strong host-guest van
      der Waals interactions in addition to the hydrophobic effect.

PMID- 18624423
TI  - Enumeration of not-yet-synthesized zeolitic zinc imidazolate MOF networks: a
      topological and DFT approach.
AB  - Twenty-one zeolitic imidazolate metal-organic frameworks based on Zn connectors
      (ZIFs) are derived and compared to known imidazolate networks. Not-yet
      synthesized zinc imidazolates are identified on the basis of DFT total energy
      scoring. The structure with lowest energy is not porous and represents an unusual
      structure type with zni topology. Total energy scoring indicates the lcs and pcb
      networks as reliable ZIF candidates. The intrinsic channel chirality of the lcs
      network makes this rare topology an attractive target for the synthetic effort.
      Among the porous ZIFs candidates, the sodalite type, sod, is also found.

PMID- 18624424
TI  - Size-dependent thermodynamic properties of metallic nanowires.
AB  - Analytical models for size-dependent melting temperature Tm(D), melting enthalpy
      DeltaHm(D), and surface energy gammasv(D) of metallic nanowires have been
      proposed in terms of the unified nanothermodynamical model where D denotes the
      diameter of nanowire. As D decreases, Tm(D), DeltaHm(D), and gammasv(D) functions
      are found to decrease almost with the same size-dependent trend. Due to the
      inclusion of the effect of dimensionality, the developed model can be applied to
      other low-dimensional systems. It is found that the ratio of depression of these
      thermodynamic parameters for spherical nanoparticle, nanowire, and thin film is
      3:2:1 when D is large enough (>20h with h being the atomic diameter). The
      validity of the model is verified by the data of experiments, molecular dynamics
      simulations, and other theoretical models.

PMID- 18624426
TI  - Symposium on the chemistry and toxicology of acrylamide.

PMID- 18624425
TI  - Development of a stable isotope dilution assay for the quantitation of
      glycidamide and its application to foods and model systems.
AB  - On the basis of a stable isotope dilution assay and derivatization with 2
      mercaptobenzoic acid, the presence of the carcinogenic glycidamide ( 2) in
      processed foods was verified for the first time. Using (13)C-labeled 2 as the
      internal standard and the formation of the thioether derivatives, a new stable
      isotope dilution assay for the quantitation of 2 was developed. Application of
      the method on several potato samples revealed amounts between 0.3 and 1.5 mug/kg
      depending on the processing conditions. In a model experiment, the formation of 2
      by an epoxidation of the double bond in acrylamide, that is, by a reaction with
      linoleic acid hydroperoxides, was established. This result was in good agreement
      with data showing that French fries processed in sunflower oil, which is high in
      linoleic acid, contained more 2 as compared to fries prepared in coconut oil. The
      derivatization procedure allows the simultaneous quantitation of acrylamide and
      glycidamide in foods.

PMID- 18624427
TI  - Acrylamide: a dietary carcinogen formed in vivo?
AB  - Acrylamide, a chemical formed during heating of human foods, reacts with N
      terminal valine in hemoglobin (Hb) and forms stable reaction products (adducts).
      These adducts to N-terminal valine in Hb have been used to estimate daily intake
      of acrylamide. Daily intake of acrylamide estimated from Hb adduct levels was
      higher than daily intake estimated from dietary questionnaires, possibly
      indicating other sources of exposures. Therefore, in this study the possible
      endogenous formation of acrylamide was investigated by treating mice with FeSO 4,
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloric acid (MPTP), or
      methamphetamine (METH). Acrylamide Hb adducts were determined, and a significant
      increase ( p < 0.05) in acrylamide Hb adduct levels was observed 24 h following
      treatment with FeSO 4 and 72 h following treatment with MPTP or METH. The results
      of this study show that acrylamide Hb adduct levels are increased in mice treated
      with compounds known to induce free radicals, thus suggesting the endogenous
      production of acrylamide.

PMID- 18624428
TI  - Hemoglobin adducts and mercapturic acid excretion of acrylamide and glycidamide
      in one study population.
AB  - The aim of this study was to determine the relationship between the oxidative and
      reductive metabolic pathways of acrylamide (AA) in the nonsmoking general
      population. For the first time both the blood protein adducts and the urinary
      metabolites of AA and glycidamide (GA) were quantified in an especially designed
      study group with even distribution of age and gender. The hemoglobin adducts N
      carbamoylethylvaline (AAVal) and N-( R, S)-2-hydroxy-2-carbamoylethylvaline
      (GAVal) were detected by GC-MS/MS in all blood samples with median levels of 30
      and 34 pmol/g of globin, respectively. Concentrations ranged from 15 to 71 pmol/g
      of globin for AAVal and from 14 to 66 pmol/g of globin for GAVal. The ratio
      GAVal/AAVal was 0.4-2.7 (median = 1.1). The urinary metabolites were determined
      by LC-MS/MS. Of all urine samples examined 99% of N-acetyl- S-(2-carbamoylethyl)-
      l-cysteine (AAMA) levels and 73% of N-( R/ S)-acetyl- S-(2-carbamoyl-2
      hydroxyethyl)- l-cysteine (GAMA) levels were above the LOD (1.5 microg/L).
      Concentrations ranged from <LOD to 229 microg/L (median = 29 microg/L) for AAMA
      and from <LOD to 85 microg/L (median = 7 microg/L) for GAMA. The ratio of
      GAMA/AAMA varied from 0.004 to 1.4 (median = 0.3). Using hemoglobin adduct levels
      in blood and mercapturic acid excretion in urine for calculation of daily AA
      intake gave practically identical values. The median daily intakes were 0.43
      (0.21-1.04) microg/kg of body weight(bw)/day using Hb adducts and 0.51 (<LOD
      2.32) microg/kg of bw/day using mercapturic acids for calculations. Children take
      up approximately 1.3-1.5 times more AA per kilogram of body weight than adults.
      The ratio GAMA/AAMA is significantly higher in the group of young children (6-10
      years) with a median level of 0.5. A gender-related difference in internal
      exposure and metabolism was not observed.

PMID- 18624429
TI  - Reducing acrylamide precursors in raw materials derived from wheat and potato.
AB  - A review of agronomic and genetic approaches as strategies for the mitigation of
      acrylamide risk in wheat and potato is presented. Acrylamide is formed through
      the Maillard reaction during high-temperature cooking, such as frying, roasting,
      or baking, and the main precursors are free asparagine and reducing sugars. In
      wheat flour, acrylamide formation is determined by asparagine levels and
      asparagine accumulation increases dramatically in response to sulfur deprivation
      and, to a much lesser extent, with nitrogen feeding. In potatoes, in which sugar
      concentrations are much lower, the relationships between acrylamide and its
      precursors are more complex. Much attention has been focused on reducing the
      levels of sugars in potatoes as a means of reducing acrylamide risk. However, the
      level of asparagine as a proportion of the total free amino acid pool has been
      shown to be a key parameter, indicating that when sugar levels are limiting,
      competition between asparagine and the other amino acids for participation in the
      Maillard reaction determines acrylamide formation. Genetic approaches to reducing
      acrylamide risk include the identification of cultivars and other germplasm in
      which free asparagine and/or sugar levels are low and the manipulation of genes
      involved in sugar and amino acid metabolism and signaling. These approaches are
      made more difficult by genotype/environment interactions that can result in a
      genotype being "good" in one environment but "poor" in another. Another important
      consideration is the effect that any change could have on flavor in the cooked
      product. Nevertheless, as both wheat and potato are regarded as of relatively
      high acrylamide risk compared with, for example, maize and rice, it is essential
      that changes are achieved that mitigate the problem.

PMID- 18624430
TI  - Acrylamide carcinogenicity.
AB  - The induction of cancer by chemicals is a multiple-stage process. Acrylamide is
      carcinogenic to experimental mice and rats, causing tumors at multiple organ
      sites in both species when given in drinking water or by other means. In mice,
      acrylamide increased the incidence and multiplicity of lung tumors and skin
      tumors. In two bioassays in rats, acrylamide administered in drinking water
      consistently induced mesotheliomas of the testes, thyroid tumors, and mammary
      gland tumors. In addition, brain tumors appeared to be increased. In one of the
      rat bioassays, pituitary tumors, pheochromocytomas, uterine tumors, and pituitary
      tumors were noted. The conversion of acrylamide metabolically to the reactive,
      mutagenic, and genotoxic product, glycidamide, can occur in both rodent and
      humans. Glycidamide and frequently acrylamide have been positive for mutagenicity
      and DNA reactivity in a number of in vitro and in vivo assays. The effects of
      chronic exposure of glycidamide to rodents have not been reported. Epidemiologic
      studies of workers for possible health effects from exposures to acrylamide have
      not shown a consistent increase in cancer risk. Although an increase in the risk
      for pancreatic cancer (almost double) was seen in highly exposed workers, no
      exposure response relationship could be determined. The mode of action remains
      unclear for acrylamide-induced rodent carcinogenicity, but support for a
      genotoxic mechanism based on in vitro and in vivo DNA reactivity assays cannot be
      ruled out. In addition, the pattern of tumor formation in the rat following
      chronic exposure supports a genotoxic mode of action but also suggests a
      potential role of endocrine modification.

PMID- 18624431
TI  - Approach for cancer risk estimation of acrylamide in food on the basis of animal
      cancer tests and in vivo dosimetry.
AB  - The question about the contribution from acrylamide (AA) in food to the cancer
      risk in the general population has not yet had a satisfactory answer. One point
      of discussion is whether AA constitutes a cancer risk through its genotoxic
      metabolite, glycidamide (GA), or whether other mechanism(s) could be operating.
      Using a relative cancer risk model, an improvement of the cancer risk estimate
      for dietary AA can be obtained by estimation of the genotoxic contribution to the
      risk. One cornerstone in this model is the in vivo dose of the causative
      genotoxic agent. This paper presents an evaluation, according to this model, of
      published AA cancer tests on the basis of in vivo doses of GA in rats exposed in
      the cancer tests. The present status regarding data with importance for an
      improved estimation of the contribution from GA to the cancer risk of AA, such as
      in vivo doses measured in humans, is discussed.

PMID- 18624433
TI  - Impact of harvest year on amino acids and sugars in potatoes and effect on
      acrylamide formation during frying.
AB  - Acrylamide is formed via the Maillard reaction between reducing sugars and
      asparagine in a number of carbohydrate-rich foods during heat treatment. High
      acrylamide levels have been found in potato products processed at high
      temperatures. To examine the impact of harvest year, information on weather
      conditions during growth, that is, temperature, precipitation, and light, was
      collected, together with analytical data on the concentrations of free amino
      acids and sugars in five potato clones and acrylamide contents in potato chips
      (commonly known as crisps in Europe). The study was conducted for 3 years (2004
      2006). The contents of acrylamide precursors differed between the clones and the
      three harvest years; the levels of glucose were up to 4.2 times higher in 2006
      than in 2004 and 2005, and the levels of fructose were 5.6 times higher, whereas
      the levels of asparagine varied to different extents. The high levels of sugars
      in 2006 were probably due to the extreme weather conditions during the growing
      season, and this was also reflected in acrylamide content that was approximately
      twice as high as in preceding years. The results indicate that acrylamide
      formation is dependent not only on the content and relative amounts of sugars and
      amino acids but also on other factors, for example, the food matrix, which may
      influence the availability of the reactants to participate in the Maillard
      reaction.

PMID- 18624432
TI  - Cross-sectional study on acrylamide hemoglobin adducts in subpopulations from the
      European Prospective Investigation into Cancer and Nutrition (EPIC) Study.
AB  - Acrylamide exposure was investigated in subgroups of the EPIC study population
      (510 subjects from 9 European countries, randomly selected and stratified by age,
      gender, and smoking status) using hemoglobin adducts of acrylamide (HbAA) and its
      primary metabolite glycidamide (HbGA). Blood samples were analyzed for HbAA and
      HbGA by HPLC/MS/MS. Statistical models for HbAA and HbGA were developed including
      body mass index (BMI), educational level, and physical activity. A large
      variability in acrylamide exposure and metabolism between individuals and country
      groups was observed with HbAA and HbGA values ranging between 15-623 and 8-377
      pmol/g of Hb, respectively. Both adducts differed significantly by country, sex,
      and smoking status. HbGA values were significantly lower in high alcohol
      consumers than in moderate consumers. With increasing BMI, HbGA in nonsmokers and
      HbAA in smokers decreased significantly. In the assessment of potential health
      effects related to acrylamide exposure, country of origin, BMI, alcohol
      consumption, sex, and smoking status should be considered.

PMID- 18624434
TI  - Inhibition of rat testicular nuclear kinesins (krp2; KIFC5A) by acrylamide as a
      basis for establishing a genotoxicity threshold.
AB  - Acrylamide is a toxic substance that induces a variety of cellular responses
      including neurotoxicity, male reproductive toxicity, tumorigenicity,
      clastogenicity, and DNA alkylation. Evidence is provided that inhibition of the
      microtubule motor protein kinesin is responsible for acrylamide-induced
      clastogenicity and aneuploidy. Two kinesin motors, KIFC5A and KRP2, which are
      responsible for spindle assembly and disassembly of kinetochore MT, respectively,
      are inhibited by acrylamide. The inhibitory concentration for a response is below
      the levels shown to adversely affect the cytogenetic parameters. The relative
      contribution of these inhibitions compared to DNA alkylation is considered. The
      implications of inhibition of these kinesins as the site of action of acrylamide
      with regard to risk assessment are substantial as this event will have a
      threshold and a safe level of acrylamide can be determined.

PMID- 18624435
TI  - Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic
      modeling in human risk extrapolations for acrylamide toxicity.
AB  - The discovery of acrylamide (AA) in many common cooked starchy foods has
      presented significant challenges to toxicologists, food scientists, and national
      regulatory and public health organizations because of the potential for producing
      neurotoxicity and cancer. This paper reviews some of the underlying experimental
      bases for AA toxicity and earlier risk assessments. Then, dietary exposure
      modeling is used to estimate probable AA intake in the U.S. population, and
      physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling is used
      to integrate the findings of rodent neurotoxicity and cancer into estimates of
      risks from human AA exposure through the diet. The goal of these modeling
      techniques is to reduce the uncertainty inherent in extrapolating toxicological
      findings across species and dose by comparing common exposure biomarkers. PBPK/PD
      modeling estimated population-based lifetime excess cancer risks from average AA
      consumption in the diet in the range of 1-4 x 10 (-4); however, modeling did not
      support a link between dietary AA exposure and human neurotoxicity because
      marginal exposure ratios were 50-300 lower than in rodents. In addition, dietary
      exposure modeling suggests that because AA is found in so many common foods, even
      big changes in concentration for single foods or groups of foods would probably
      have a small impact on overall population-based intake and risk. These results
      suggest that a more holistic analysis of dietary cancer risks may be appropriate,
      by which potential risks from AA should be considered in conjunction with other
      risks and benefits from foods.

PMID- 18624436
TI  - Importance of oil degradation components in the formation of acrylamide in fried
      foodstuffs.
AB  - This study investigates the importance of selected oil degradation components and
      some analogues in the formation of acrylamide. For this, a model system
      containing silica gel, PBS buffer, and oil was heated in a closed tubular
      reactor, under practically relevant heating conditions. Several probable
      acrylamide precursors were mixed together with free asparagine in the model
      system, such as partial glycerides, glycerol, acrolein, acrylic acid, and several
      aldehydes. Only the heated model system containing acrolein and asparagine showed
      a significantly higher acrylamide content compared to the control to which only
      asparagine was added. It was postulated that a nucleophilic 1,2-addition of the
      alpha-amino group of free asparagine to the carbonyl function of acrolein would
      lead to the formation of acrylamide. This hypothesis could partially be
      confirmed, replacing acrolein with other alpha,beta-unsaturated aldehydes.
      However, the contribution of acrolein to the overall formation of acrylamide
      appeared to be negligible in the presence of a reducing sugar, indicating that in
      foodstuffs the importance of acrolein and other oil degradation products is
      probably small.

PMID- 18624437
TI  - Acrylamide-induced nerve terminal damage: relevance to neurotoxic and
      neurodegenerative mechanisms.
AB  - Acrylamide (ACR) has demonstrable neurotoxic effects in animals and humans that
      stem from its chemical behavior as a soft electrophilic alpha,beta-unsaturated
      carbonyl compound. Evidence is presented that the nerve terminal is a primary
      site of ACR action and that inhibition of neurotransmission mediates the
      development of neurological deficits. At the mechanistic level, recent proteomic,
      neurochemical, and kinetic data are considered, which suggest that ACR inhibits
      neurotransmission by disrupting presynaptic nitric oxide (NO) signaling. Nerve
      terminal damage likely mediates the neurological complications that accompany the
      occupational exposure of humans to ACR. In addition, the proposed molecular
      mechanism of synaptotoxicity has substantial implications for the pathogenesis of
      Alzheimer's disease and other neurodegenerative conditions that involve neuronal
      oxidative stress and the secondary endogenous generation of acrolein and other
      conjugated carbonyl chemicals.

PMID- 18624438
TI  - Analysis of acrylamide in a complex matrix of polyacrylamide solutions treated by
      heat and ultraviolet light.
AB  - A recently developed headspace/solid-phase microextraction/gas chromatograph (GC)
      equipped with a nitrogen-phosphorus detector (NPD) (HS/SPME/GC/NPD) method was
      used to analyze acrylamide formed in an aqueous polyacrylamide solution (25%)
      treated by heat or photo-irradiation. Original polyacrylamide contained 0.43 +/-
      0.11 microg/mL of acrylamide. When polyacrylamide solution was heated at 70
      degrees C for 16 h with 0.5% potassium persulfate, the amount of acrylamide
      increased to 1.02 +/- 0.11 microg/mL. When polyacrylamide solution was irradiated
      by UV (lambda = 300 nm) for 16 h with 0.05% 2-anthraquinone sulfate sodium salt,
      the amount of acrylamide increased to 1.14 +/- 0.54 microg/mL. Polyacrylamide has
      been used in cosmetic formulations. The present study, therefore, suggests that
      there is another route of acrylamide exposure to humans in addition to foods and
      beverages.

PMID- 18624439
TI  - Reduction of acrylamide level in french fries by employing a temperature program
      during frying.
AB  - In this study, the effect of employing an oil temperature program during frying
      on the acrylamide content of French fries was investigated. The frying conditions
      that could lead to lower acrylamide levels in French fries were first simulated
      by means of an experimentally validated frying model. Then, experiments were
      conducted to test the simulated conditions in real frying process. Different
      time/temperature combinations (4 min at 170 degrees C, 2 min at 170 degrees C + 2
      min at 150 degrees C, 1 min at 170 degrees C + 3 min at 150 degrees C, 1 min at
      190 degrees C + 3 min at 150 degrees C) were employed for frying potato strips
      (8.5 x 8.5 x 70 mm), and the resultant acrylamide levels were determined with a
      gas chromatography-mass spectrometry (GC-MS) method. The results indicated that
      acrylamide levels in French fries can be reduced by half if the final stage of
      the frying process employs a lower oil temperature. Therefore, the method appears
      to be an effective way of controlling the acrylamide level in the final product.

PMID- 18624440
TI  - Correlations between the amounts of free asparagine and saccharides present in
      commercial cereal flours in the United Kingdom and the generation of acrylamide
      during cooking.
AB  - A range of commercially available cereals (mainly rye and wheat) used to
      manufacture U.K. bakery products were obtained, and the levels of free amino
      acids and sugars were measured. Selected samples were cooked as flours and doughs
      to generate acrylamide and the data compared with those obtained from a model
      system using dough samples that had been additionally fortified with asparagine
      (Asn) and sugars (glucose, fructose, maltose, and sucrose). In cooked flours and
      doughs, Asn was the key determinant of acrylamide generation. A significant
      finding for biscuit and rye flours was that levels of Asn were correlated with
      fructose and glucose. The results suggest that for these commercial cereals,
      selection based on low fructose and glucose contents, and hence low asparagine,
      could be beneficial in reducing acrylamide in products (e.g., crackers and
      crispbreads) that have no added sugars.

PMID- 18624441
TI  - Acrylamide and pyrazine formation in model systems containing asparagine.
AB  - The effect of different sugars and glyoxal on the formation of acrylamide in low
      moisture starch-based model systems was studied, and kinetic data were obtained.
      Glucose was more effective than fructose, tagatose, or maltose in acrylamide
      formation, whereas the importance of glyoxal as a key sugar fragmentation
      intermediate was confirmed. Glyoxal formation was greater in model systems
      containing asparagine and glucose rather than fructose. A solid phase
      microextraction GC-MS method was employed to determine quantitatively the
      formation of pyrazines in model reaction systems. Substituted pyrazine formation
      was more evident in model systems containing fructose; however, the unsubstituted
      homologue, which was the only pyrazine identified in the headspace of glyoxal
      asparagine systems, was formed at higher yields when aldoses were used as the
      reducing sugar. Highly significant correlations were obtained for the
      relationship between pyrazine and acrylamide formation. The importance of the
      tautomerization of the asparagine-carbonyl decarboxylated Schiff base in the
      relative yields of pyrazines and acrylamide is discussed.

PMID- 18624442
TI  - Dietary acrylamide exposure estimates for the United Kingdom and Ireland:
      comparison between semiprobabilistic and probabilistic exposure models.
AB  - Since the discovery of acrylamide in foods, there have been many calculations of
      dietary exposure. Total diet studies have been commonly used to estimate consumer
      exposure of acrylamide; however, these often fall short in evaluating true
      exposure levels because of limitations in small occurrence data sets. Dietary
      exposure to acrylamide can also be estimated by use of modeling packages. The
      U.K. Food Standards Agency and the Food Safety Authority of Ireland have prepared
      estimates for dietary acrylamide exposure using semiprobabilistic and
      probabilistic modeling. Occurrence data were obtained from the European Union
      acrylamide monitoring database, whereas consumption data were obtained from the
      relevant U.K. and Irish National Diet and Nutrition Surveys. The mean adult U.K.
      consumer exposure was estimated as 0.61 microg/kg of body weight (bw)/day and
      high-level adult consumer exposure (P97.5) as 1.29 microg/kg of bw/day. The mean
      adult Irish consumer exposure was estimated as 0.59 microg/kg of bw/day and the
      high-level adult consumer exposure (P97.5) as 1.75 microg/kg of bw/day. Owing to
      the wide range of acrylamide levels in foods, semiprobabilistic modeling does not
      always provide an accurate picture of dietary exposure levels and patterns.
      Therefore, a comparison of semiprobabilistic assessments to probabilistic
      assessments of U.K. and Irish dietary exposure estimates of certain food groups
      is provided.

PMID- 18624443
TI  - Acrylamide intake through diet and human cancer risk.
AB  - More than one-third of the calories consumed by U.S. and European populations
      contain acrylamide, a substance classified as a "probable human carcinogen" based
      on laboratory data. Thus, it is a public health concern to evaluate whether
      intake of acrylamide at levels found in the food supply is an important cancer
      risk factor. Mean dietary intake of acrylamide in adults averages 0.5 microg/kg
      of body weight per day, whereas intake is higher among children. Several
      epidemiological studies examining the relationship between dietary intake of
      acrylamide and cancers of the colon, rectum, kidney, bladder, and breast have
      been undertaken. These studies found no association between intake of specific
      foods containing acrylamide and risk of these cancers. Moreover, there was no
      relationship between estimated acrylamide intake in the diet and cancer risk.
      Results of this research are compared with other epidemiological studies, and the
      findings are examined in the context of data from animal models. The importance
      of epidemiological studies to establish the public health risk associated with
      acrylamide in food is discussed, as are the limitations and future directions of
      such studies.

PMID- 18624444
TI  - Effects of plant sulfur nutrition on acrylamide and aroma compounds in cooked
      wheat.
AB  - Wheat flour from plants deficient in sulfur has been shown to contain
      substantially higher levels of free amino acids, particularly asparagine and
      glutamine, than flour from wheat grown where sulfur nutrition was sufficient.
      Elevated levels of asparagine resulted in acrylamide levels up to 6 times higher
      in sulfur-deprived wheat flour, compared with sulfur-sufficient wheat flour, for
      three varieties of winter wheat. The volatile compounds from flour, heated at 180
      degrees C for 20 min, have been compared for these three varieties of wheat grown
      with and without sulfur fertilizer. Approximately 50 compounds were quantified in
      the headspace extracts of the heated flour; over 30 compounds were affected by
      sulfur fertilization, and 15 compounds were affected by variety. Unsaturated
      aldehydes formed from aldol condensations, Strecker aldehydes, alkylpyrazines,
      and low molecular weight alkylfurans were found at higher concentrations in the
      sulfur-deficient flour, whereas low molecular weight pyrroles and thiophenes and
      sugar breakdown products were found at higher concentrations in the sulfur
      sufficient flour. The reasons for these differences and the relationship between
      acrylamide formation and aroma volatile formation are discussed.

PMID- 18624446
TI  - Determination of acrylamide during roasting of coffee.
AB  - In this study different Arabica and Robusta coffee beans from different regions
      of the world were analyzed for acrylamide after roasting in a laboratory roaster.
      Due to the complex matrix and the comparably low selectivity of the LC-MS at m/ z
      72, acrylamide was analyzed after derivatization with 2-mercaptobenzoic acid at
      m/ z 226. Additionally, the potential precursors of acrylamide (3
      aminopropionamide, carbohydrates, and amino acids) were studied. The highest
      amounts of acrylamide formed in coffee were found during the first minutes of the
      roasting process [3800 ng/g in Robusta ( Coffea canephora robusta) and 500 ng/g
      in Arabica ( Coffea arabica)]. When the roasting time was increased, the
      concentration of acrylamide decreased. It was shown that especially the roasting
      time and temperature, species of coffee, and amount of precursors in raw material
      had an influence on acrylamide formation. Robusta coffee contained significantly
      larger amounts of acrylamide (mean = 708 ng/g) than Arabica coffee (mean = 374
      ng/g). Asparagine is the limiting factor for acrylamide formation in coffee. 3
      Aminopropionamide formation was observed in a dry model system with mixtures of
      asparagine with sugars (sucrose, glucose). Thermal decarboxylation and
      elimination of the alpha-amino group of asparagine at high temperatures (>220
      degrees C) led to a measurable but low formation of acrylamide.

PMID- 18624445
TI  - Genotoxicity of glycidamide in comparison to 3-N-nitroso-oxazolidin-2-one.
AB  - Acrylamide (AA) is generated by thermal processing of foods, depending on
      processing conditions and precursor availability. AA is not genotoxic by itself
      but becomes activated to its genotoxic metabolite glycidamide (GA) via
      epoxidation, mediated primarily by cytochrome P450 2E1. In the Comet assay in V79
      cells and in human lymphocytes, GA induced DNA damage down to 300 microM
      concentration (4 h). After post-treatment with the DNA repair enzyme
      formamidopyrimidine-DNA-glycosylase (FPG), DNA damage became already detectable
      at 10 microM (4 h). By comparison, the N-nitroso compound 3- N-nitroso-oxazolidin
      2-one (NOZ-2) is a much stronger genotoxic agent, significantly inducing DNA
      damage already at 15 min (3 microM). Post-treatment with FPG in this case did not
      enhance response. GA induced DNA damage in V79 cells rather slowly, with first
      response detectable at 4 h. The hPRT forward mutation test encompasses 5 days of
      expression time during which also repair can take place. GA-induced hPRT
      mutations only became detectable at concentrations of 800 microM and above. This
      is 80-fold higher than the lowest significant response to GA in the Comet assay
      (10 microM with FPG). In contrast, NOZ-2 was as effective in the hPRT test as in
      the Comet assay (3 microM). These results demonstrate substantial differences in
      the genotoxic potency of GA and NOZ-2. Whereas NOZ-2 is a pontent genotoxic
      mutagen, GA in comparison shows only low genotoxic and mutagenic potential,
      presumably as a result, at least in part, of preferential N7-G alkylation.

PMID- 18624447
TI  - Further insight into thermally and pH-induced generation of acrylamide from
      glucose/asparagine model systems.
AB  - On the basis of numerous studies on the mechanism of formation of acrylamide (AA)
      from asparagine and reducing sugars, the decarboxylated Schiff base [ N-( d
      glucos-1-yl)-3'-aminopropionamide] and its corresponding Amadori product [ N-(1
      deoxy- d-fructos-1-yl)-3'-aminopropionamide) are considered to be possible direct
      precursors in addition to 3-aminopropionamide (AP). Furthermore, the mechanism of
      decarboxylation of the initially formed N-( d-glucos-1-yl)asparagine to generate
      the above-mentioned precursors also remains to be confirmed. To identify the
      relative importance of AA precursors, the decarboxylated Amadori product (AP ARP)
      and the corresponding Schiff base were synthesized and their relative abilities
      to generate AA under dry and wet heating conditions were studied. Under both
      conditions, the N-( d-glucos-1-yl)-3'-aminopropionamide had the highest intrinsic
      ability to be converted into AA. In the dry model system, the increase was almost
      4-fold higher than the corresponding AP ARP or AP; however, in the wet system,
      the increase was 2-fold higher relative to AP ARP but >20-fold higher relative to
      AP. In addition, to gain further insight into the decarboxylation step, the amino
      acid/sugar reactions were analyzed by FTIR to monitor the formation of the
      previously proposed 5-oxazolidinone intermediate known to exhibit a peak in the
      range of 1770-1810 cm (-1). Spectroscopic studies clearly indicated the formation
      of an intense peak in the indicated range, the precise wavelength being dependent
      on the amino acid and the sugar used. The identity of the peak was verified by
      observing a 40 cm (-1) shift when [(13)C-1]-labeled amino acid was used.

PMID- 18624448
TI  - Identification and monitoring of intermediates and products in the acrylamide
      pathway using online analysis.
AB  - Acrylamide formation under controlled processing conditions was studied in a
      starch matrix by analyzing volatile compounds in the gas phase using online mass
      spectrometry. Compounds were identified using mass spectral analysis, authentic
      standards, and the labeling patterns from isotopically labeled asparagine and
      sugars. Acrylamide, 3-aminopropanamide, methylpyrazine, 3-oxopropanamide, and
      aminopropan-2-one were assigned to the ions at m/ z 72, 89, 95, 88, and 74,
      respectively. Ion m/ z 60 was proposed as the transamination product of glyoxal,
      but labeling experiments did not support this assignment. Temporal formation of
      acrylamide and related compounds was studied in 51 samples containing asparagine
      and selected sugars or carbonyls. Data from the experiments were analyzed to
      investigate correlations between the amounts of acrylamide, intermediates, and
      pyrazines formed. A strong correlation between 3-aminopropanamide and acrylamide
      was found in all samples, whereas other correlations were reactant specific.
      Preliminary multiway analysis of the data identified temporal similarities in the
      ion profiles and showed that dynamic monitoring can follow the production and
      utilization of intermediates leading to acrylamide.

PMID- 18624449
TI  - Contribution of lipid oxidation products to acrylamide formation in model
      systems.
AB  - The reactions of asparagine with methyl linoleate ( 1), methyl 13
      hydroperoxyoctadeca-9,11-dienoate ( 2), methyl 13-hydroxyoctadeca-9,11-dienoate (
      3), methyl 13-oxooctadeca-9,11-dienoate ( 4), methyl 9,10-epoxy-13-hydroxy-11
      octadecenoate ( 5), methyl 9,10-epoxy-13-oxo-11-octadecenoate ( 6), 2,4
      decadienal ( 7), 2-octenal ( 8), 4,5-epoxy-2-decenal ( 9), and benzaldehyde ( 10)
      were studied to determine the potential contribution of lipid derivatives to
      acrylamide formation in heated foodstuffs. Reaction mixtures were heated in
      sealed tubes for 10 min at 180 degrees C under nitrogen. The reactivity of the
      assayed compounds was 7 >> 9 > 4 > 2 >> 8 approximately 6 >> 10 approximately 5.
      The presence of compounds 1 and 3 did not result in the formation of acrylamide.
      These results suggested that alpha,beta,gamma,delta-diunsaturated carbonyl
      compounds were the most reactive compounds for this reaction followed by lipid
      hydroperoxides, more likely as a consequence of the thermal decomposition of
      these last compounds to produce alpha,beta,gamma,delta-diunsaturated carbonyl
      compounds. However, in the presence of glucose this reactivity changed, and
      compound 1/glucose mixtures showed a positive synergism (synergism factor = 1.6),
      which was observed neither in methyl stearate/glucose mixtures nor in the
      presence of antioxidants. This synergism is proposed to be a consequence of the
      formation of free radicals during the asparagine/glucose Maillard reaction, which
      oxidized the lipid and facilitated its reaction with the amino acid. These
      results suggest that both unoxidized and oxidized lipids are able to contribute
      to the conversion of asparagine into acrylamide, but unoxidized lipids need to be
      oxidized as a preliminary step.

PMID- 18624450
TI  - Effectiveness of methods for reducing acrylamide in bakery products.
AB  - Pilot-scale bread, biscuit, and cracker doughs have been baked to assess how well
      recipe changes could reduce acrylamide in commercial bakery products. Removing
      ammonium-based raising agents was beneficial in biscuits. In doughs, long yeast
      fermentations were an effective way of reducing asparagine levels and hence
      acrylamide. At moderate fermentation times fructose levels increased, but the
      yeast later absorbed this, so the net effect on acrylamide was beneficial. Metal
      ions such as calcium reduced acrylamide when added as the carbonate or chloride.
      Hence, the fortification of flour with calcium carbonate, over and above its
      natural mineral content, has an additional benefit. However, some other possible
      methods of adding calcium to bakery doughs, for example, via the permitted
      preservative calcium propionate, were not beneficial. Amino acid addition to
      doughs gave modest reductions in acrylamide. Lowering the dough pH reduced
      acrylamide, but at the expense of higher levels of other process contaminants
      such as 3-monochloropropane-1,2-diol (3-MCPD).

PMID- 18624451
TI  - Inhibition of acrylamide toxicity in mice by three dietary constituents.
AB  - The inhibitory effects of three dietary constituents, tea polyphenols,
      resveratrol, and diallyl trisulfide, on acrylamide-biomacromolecule (liver DNA,
      protamine, and hemoglobin) adduct formation at human exposure level were studied
      by accelerator mass spectrometry. The results demonstrated that the three dietary
      constituents all significantly inhibited the formation of acrylamide adducts with
      liver DNA, whereas tea polyphenols and diallyl trisulfide reduced protamine and
      hemoglobin adducts, respectively. Further biochemical studies showed that
      acrylamide could significantly inactivate creatine kinase and glutathione S
      transferase and deplete glutathione. When the inhibitors were cotreated with
      acrylamide, all of them could effectively recover the activities of creatine
      kinase. In addition, tea polyphenols and diallyl trisulfide could increase
      glutathione S-transferase activity remarkably. On the basis of these results,
      mechanisms of the effects are discussed. This study might provide a beneficial
      guide to people's diet for the purpose of reducing the harmful effect of
      acrylamide.

PMID- 18624452
TI  - Review of methods for the reduction of dietary content and toxicity of
      acrylamide.
AB  - Potentially toxic acrylamide is largely derived from heat-induced reactions
      between the amino group of the free amino acid asparagine and carbonyl groups of
      glucose and fructose in cereals, potatoes, and other plant-derived foods. This
      overview surveys and consolidates the following dietary aspects of acrylamide:
      distribution in food originating from different sources; consumption by diverse
      populations; reduction of the acrylamide content in the diet; and suppression of
      adverse effects in vivo. Methods to reduce adverse effects of dietary acrylamide
      include (a) selecting potato, cereal, and other plant varieties for dietary use
      that contain low levels of the acrylamide precursors, namely, asparagine and
      glucose; (b) removing precursors before processing; (c) using the enzyme
      asparaginase to hydrolyze asparagine to aspartic acid; (d) selecting processing
      conditions (pH, temperature, time, processing and storage atmosphere) that
      minimize acrylamide formation; (e) adding food ingredients (acidulants, amino
      acids, antioxidants, nonreducing carbohydrates, chitosan, garlic compounds,
      protein hydrolysates, proteins, metal salts) that have been reported to prevent
      acrylamide formation; (f) removing/trapping acrylamide after it is formed with
      the aid of chromatography, evaporation, polymerization, or reaction with other
      food ingredients; and (g) reducing in vivo toxicity. Research needs are suggested
      that may further facilitate reducing the acrylamide burden of the diet.
      Researchers are challenged to (a) apply the available methods and to minimize the
      acrylamide content of the diet without adversely affecting the nutritional
      quality, safety, and sensory attributes, including color and flavor, while
      maintaining consumer acceptance; and (b) educate commercial and home food
      processors and the public about available approaches to mitigating undesirable
      effects of dietary acrylamide.

PMID- 18624453
TI  - Sequential interpenetrating polymer networks produced from vegetable oil based
      polyurethane and poly(methyl methacrylate).
AB  - Sequential interpenetrating polymer networks (IPNs) were prepared using
      polyurethane produced from a canola oil based polyol with primary terminal
      functional groups and poly(methyl methacrylate) (PMMA). The properties of the
      material were studied and compared to the IPNs made from commercial castor oil
      using dynamic mechanical analysis, differential scanning calorimetry, as well as
      tensile measurements. The morphology of the IPNs was investigated using scanning
      electron microscopy and transmission electron microscopy. The chemical diversity
      of the starting materials allowed the evaluation of the effects of dangling
      chains and graftings on the properties of the IPNs. The polymerization process of
      canola oil based IPNs was accelerated because of the utilization of polyol with
      primary functional groups, which efficiently lessened the effect of dangling
      chains and yielded a higher degree of phase mixing. The mechanical properties of
      canola oil based IPNs containing more than 75 wt % PMMA were comparable to the
      corresponding castor oil based IPNs; both were superior to those of the
      constituent polymers due to the finely divided rubber and plastic combination
      structures in these IPNs. However, when PMMA content was less than 65 wt %,
      canola oil based IPNs exhibited a typical mechanical behavior of rigid plastics,
      whereas castor oil based IPNs showed a typical mechanical behavior of soft
      rubber. It is proposed that these new IPN materials with high performance
      prepared from alternative renewable resources can prove to be valuable
      substitutes for existing materials in various applications.

PMID- 18624454
TI  - Stimuli responsive self-assembled hydrogel of a low molecular weight free
      dipeptide with potential for tunable drug delivery.
AB  - Bottom-up fabrication by molecular self-assembly is now widely recognized as a
      potent method for generating interesting and functional nano- and mesoscale
      structures. Hydrogels from biocompatible molecules are an interesting class of
      mesoscale assemblies with potential biomedical applications. The self-assembly of
      a proteolysis resistant aromatic dipeptide containing a conformational
      constraining residue (DeltaPhe) into a stable hydrogel has been studied in this
      work. The reported dipeptide has free -N and -C termini. The hydrogel was self
      supportive, was fractaline in nature, and possessed high mechanical strength. It
      was responsive to environmental conditions like pH, temperature, and ionic
      strength. The gel matrix could encapsulate and release bioactive molecules in a
      sustained manner. The described hydrogel showed no observable cytotoxicity to the
      HeLa and L929 cell lines in culture.

PMID- 18624455
TI  - The crystal structure of human Delta4-3-ketosteroid 5beta-reductase defines the
      functional role of the residues of the catalytic tetrad in the steroid double
      bond reduction mechanism.
AB  - The 5beta-reductases (AKR1D1-3) are unique enzymes able to catalyze efficiently
      and in a stereospecific manner the 5beta-reduction of the C4-C5 double bond found
      into Delta4-3-ketosteroids, including steroid hormones and bile acids. Multiple
      sequence alignments and mutagenic studies have already identified one of the
      residues presumably located at their active site, Glu 120, as the major molecular
      determinant for the unique activity displayed by 5beta-reductases. To define the
      exact role played by this glutamate in the catalytic activity of these enzymes,
      biochemical and structural studies on human 5beta-reductase (h5beta-red) have
      been undertaken. The crystal structure of h5beta-red in a ternary complex with
      NADP (+) and 5beta-dihydroprogesterone (5beta-DHP), the product of the 5beta
      reduction of progesterone (Prog), revealed that Glu 120 does not interact
      directly with the other catalytic residues, as previously hypothesized, thus
      suggesting that this residue is not directly involved in catalysis but could
      instead be important for the proper positioning of the steroid substrate in the
      catalytic site. On the basis of our structural results, we thus propose a
      realistic scheme for the catalytic mechanism of the C4-C5 double bond reduction.
      We also propose that bile acid precursors such as 7alpha-hydroxy-4-cholesten-3
      one and 7alpha,12alpha-dihydroxy-4-cholesten-3-one, when bound to the active site
      of h5beta-red, can establish supplementary contacts with Tyr 26 and Tyr 132, two
      residues delineating the steroid-binding cavity. These additional contacts very
      likely account for the higher activity of h5beta-red toward the bile acid
      intermediates versus steroid hormones. Finally, in light of the structural data
      now available, we attempt to interpret the likely consequences of mutations
      already identified in the gene encoding the h5beta-red enzyme which lead to a
      reduction of its enzymatic activity and which can progress to severe liver
      function failure.

PMID- 18624456
TI  - Inverted microcontact printing on polystyrene-block-poly(tert-butyl acrylate)
      films: a versatile approach to fabricate structured biointerfaces across the
      length scales.
AB  - The combination of the recently introduced soft lithographic technique of
      inverted microcontact printing (i-muCP) and spin-coated films of polystyrene-
      block-poly( tert-butyl acrylate) (PS 690- b-P tBA 1210) as a reactive platform is
      shown to yield a versatile approach for the facile fabrication of topographically
      structured and chemically patterned biointerfaces with characteristic spacings
      and distances that cross many orders of magnitude. The shortcomings of
      conventional muCP in printing of small features with large spacings, due to the
      collapse of small or high aspect ratio stamp structures, are circumvented in i
      muCP by printing reactants using a featureless elastomeric stamp onto a
      topographically structured reactive polymer film. Prior to molecular transfer,
      the substrate-supported PS 690- b-P tBA 1210 films were structured by imprint
      lithography resulting in lateral and vertical feature sizes between >50 microm
      150 nm and >1.0 microm-18 nm, respectively. Time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) and water contact angle measurements provided evidence
      for the absence of surface chemical transformations during the imprinting step.
      Following the previously established hydrolysis and activation protocol with
      trifluoroacetic acid and N-hydroxysuccinimide, amino end-functionalized
      poly(ethylene glycol) (PEG-NH 2), as well as bovine serum albumin and fibronectin
      as model proteins, were successfully transferred by i-muCP and coupled
      covalently. As shown, i-muCP yields increased PEG coverages and thus improved
      performance in suppressing nonspecific adsorption of proteins by exploiting the
      high local concentrations in the micro- and nanocontacts during molecular
      transfer. The i-muCP strategy provides access to versatile biointerface platforms
      patterned across the length scales, as shown for guided cancer cell adhesion,
      which opens the pathway for systematic cell-surface interaction studies.

PMID- 18624459
TI  - Predictive first-principles simulations of strain-induced phenomena at water
      silica nanotube interfaces.
AB  - Via ab initio simulation, we study the behavior of interfaces of water with
      silica nanotubes. We find profound differences between zero and finite tensile
      strains and between unconfined (exterior) versus confined (interior) water. For
      these distinct cases, we characterize the fracture dynamics of the silica
      nanotube and the underlying physical mechanisms.

PMID- 18624460
TI  - Accurate solid-state band gaps via screened hybrid electronic structure
      calculations.
AB  - The band energy differences of solids calculated with screened hybrid density
      functionals, such as the functional of Heyd-Scuseria-Ernzerhof (HSE), reproduce
      experimental band gaps with a high degree of accuracy. This unexpected result is
      here rationalized by observing that band energy differences obtained from
      generalized Kohn-Sham calculations with screened (short-range) Hartree-Fock-type
      exchange approach the excitation energies obtained via time-dependent density
      functional calculations with the corresponding unscreened functional. The latter
      are expected to be the accurate predictions of the experimental optical
      absorption spectra. While the optimum screening parameter (omega) is system
      dependent, the HSE standard value of omega=0.11 bohr(-1) represents a reasonable
      compromise across diverse systems.

PMID- 18624461
TI  - A hierarchical construction scheme for accurate potential energy surface
      generation: an application to the F+H2 reaction.
AB  - We present a hierarchical construction scheme for accurate ab initio potential
      energy surface generation. The scheme is based on the observation that when
      molecular configuration changes, the variation in the potential energy difference
      between different ab initio methods is much smaller than the variation for
      potential energy itself. This means that it is easier to numerically represent
      energy difference to achieve a desired accuracy. Because the computational cost
      for ab initio calculations increases very rapidly with the accuracy, one can gain
      substantial saving in computational time by constructing a high accurate
      potential energy surface as a sum of a low accurate surface based on extensive ab
      initio data points and an energy difference surface for high and low accuracy ab
      initio methods based on much fewer data points. The new scheme was applied to
      construct an accurate ground potential energy surface for the FH(2) system using
      the coupled-cluster method and a very large basis set. The constructed potential
      energy surface is found to be more accurate on describing the resonance states in
      the FH(2) and FHD systems than the existing surfaces.

PMID- 18624462
TI  - Stability and interface quality of GeO2 films grown on Ge by atomic oxygen
      assisted deposition.
AB  - The composition of GeO(2) films grown on Ge has been studied for different
      molecular deposition processes and after exposure to ambient air. The
      stoichiometry, the interaction with moisture, and the interfacial details of the
      films are shown to be dramatically process dependent.

PMID- 18624463
TI  - Femtosecond real-time probing of transition state dynamics in a surface
      photoreaction: methyl desorption from CH3I on MgO(100).
AB  - A novel experimental approach to the investigation of surface adsorbate reaction
      dynamics is presented. The direct time-resolved monitoring of the surface
      reaction transition state and product formation dynamics were accomplished via
      pump-probe mass spectrometry. As an example, methyl iodide molecules adsorbed at
      submonolayer coverage on an ultrathin magnesia film on Mo(100) were photoexcited
      to the A-band by ultrafast laser pulse irradiation. Employing time-delayed
      multiphoton ionization the dynamics of the dissociative methyl iodide transition
      state and of the emerging methyl photoproduct could be detected with femtosecond
      resolution. The reaction times deduced from the temporal evolution of the methyl
      ion mass signal indicate a strong interaction of the methyl fragment with the
      substrate surface prior to desorption.

PMID- 18624464
TI  - Inclusion of explicit electron-proton correlation in the nuclear-electronic
      orbital approach using Gaussian-type geminal functions.
AB  - The nuclear-electronic orbital explicitly correlated Hartree-Fock (NEO-XCHF)
      approach for including electron-proton correlation in mixed nuclear-electronic
      wavefunctions is presented. A general ansatz for the nuclear-electronic
      wavefunction that includes explicit dependence on the nuclear-electronic
      distances with Gaussian-type geminal functions is proposed. Based on this ansatz,
      expressions are derived for the total energy and the electronic and nuclear Fock
      operators for multielectron systems. The explicit electron-proton correlation is
      incorporated directly into the self-consistent-field procedure for optimizing the
      nuclear-electronic wavefunction. This approach is computationally practical for
      many-electron systems because only a relatively small number of nuclei are
      treated quantum mechanically, and only electron-proton correlation is treated
      explicitly. Electron-electron correlation can be included by combining the NEO
      XCHF approach with perturbation theory, density functional theory, and
      multiconfigurational methods. Previous nuclear-electronic orbital-based methods
      produce nuclear densities that are too localized, resulting in abnormally high
      stretching frequencies and inaccuracies in other properties relying on these
      densities. The application of the NEO-XCHF approach to the [He-H-He](+) model
      system illustrates that this approach includes the significant electron-proton
      correlation, thereby leading to an accurate description of the nuclear density.
      The agreement between the proton densities obtained with the NEO-XCHF and grid
      based methods validates the underlying theory and the implementation of the NEO
      XCHF method.

PMID- 18624465
TI  - The influence of thermostats and manostats on reverse nonequilibrium molecular
      dynamics calculations of fluid viscosities.
AB  - Reverse nonequilibrium molecular dynamics to calculate the shear viscosity of
      Lennard-Jones liquids was extended to simulations at constant number of
      particles, constant volume, and constant pressure using a Berendsen thermostat
      and a Berendsen manostat. Using additional systems such as water and hexane, we
      also report on the performance of shear viscosity calculations of systems with
      electrostatic and nontrivial intramolecular interactions when a manostat is
      applied. We compare the shear viscosities of simulations using no coupling, only
      temperature coupling, and temperature and pressure coupling and characterize
      discrepancies, where observed. From this, we deduce guidelines for when and how
      manostats can be usefully applied in reverse nonequilibrium simulations.

PMID- 18624466
TI  - Rotationally invariant ab initio evaluation of Coulomb and exchange parameters
      for DFT+U calculations.
AB  - Conventional density functional theory (DFT) fails for strongly correlated
      electron systems due to large intra-atomic self-interaction errors. The DFT+U
      method provides a means of overcoming these errors through the use of a
      parametrized potential that employs an exact treatment of quantum mechanical
      exchange interactions. The parameters that enter into this potential correspond
      to the spherically averaged intra-atomic Coulomb (U) and exchange (J)
      interactions. Recently, we developed an ab initio approach for evaluating these
      parameters on the basis of unrestricted Hartree-Fock (UHF) theory, which has the
      advantage of being free of self-interaction errors and does not require
      experimental input [Mosey and Carter, Phys. Rev. B 76, 155123 (2007)]. In this
      work, we build on that method to develop a more robust and convenient ab initio
      approach for evaluating U and J. The new technique employs a relationship between
      U and J and the Coulomb and exchange integrals evaluated using the entire set of
      UHF molecular orbitals (MOs) for the system. Employing the entire set of UHF MOs
      renders the method rotationally invariant and eliminates the difficulty in
      selecting unambiguously the MOs that correspond to localized states. These
      aspects overcome two significant deficiencies of our earlier method. The new
      technique is used to evaluate U and J for Cr(2)O(3), FeO, and Fe(2)O(3). The
      resulting values of U-J are close to empirical estimates of this quantity for
      each of these materials and are also similar to results of constrained DFT
      calculations. DFT+U calculations using the ab initio parameters yield results
      that are in good agreement with experiment. As such, this method offers a means
      of performing accurate and fully predictive DFT+U calculations of strongly
      correlated electron materials.

PMID- 18624467
TI  - Second order coalescence conditions of molecular wave functions.
AB  - Kato's cusp condition gives the exact first order dependence of molecular wave
      functions on interparticle separation near the coalescence of two charged
      particles. We derive conditions correct to second order in interparticle
      separation, which concern second order derivatives of the wave function at the
      coalescence point. For identical particle coalescence, we give equations correct
      to third order. In addition to a universal, particle dependent term, a system and
      state dependent term arises in the higher order conditions, which we interpret as
      an effect of Coulombic screening. We apply our analysis to the standard orbital
      based methods of quantum chemistry and discuss the implications for Jastrow- and
      R12-type correlation factors.

PMID- 18624468
TI  - Essential energy space random walks to accelerate molecular dynamics simulations:
      convergence improvements via an adaptive-length self-healing strategy.
AB  - Recently, accelerated molecular dynamics (AMD) technique was generalized to
      realize essential energy space random walks so that further sampling enhancement
      and effective localized enhanced sampling could be achieved. This method is
      especially meaningful when essential coordinates of the target events are not
      priori known; moreover, the energy space metadynamics method was also introduced
      so that biasing free energy functions can be robustly generated. Despite the
      promising features of this method, due to the nonequilibrium nature of the
      metadynamics recursion, it is challenging to rigorously use the data obtained at
      the recursion stage to perform equilibrium analysis, such as free energy surface
      mapping; therefore, a large amount of data ought to be wasted. To resolve such
      problem so as to further improve simulation convergence, as promised in our
      original paper, we are reporting an alternate approach: the adaptive-length self
      healing (ALSH) strategy for AMD simulations; this development is based on a
      recent self-healing umbrella sampling method. Here, the unit simulation length
      for each self-healing recursion is increasingly updated based on the Wang-Landau
      flattening judgment. When the unit simulation length for each update is long
      enough, all the following unit simulations naturally run into the equilibrium
      regime. Thereafter, these unit simulations can serve for the dual purposes of
      recursion and equilibrium analysis. As demonstrated in our model studies, by
      applying ALSH, both fast recursion and short nonequilibrium data waste can be
      compromised. As a result, combining all the data obtained from all the unit
      simulations that are in the equilibrium regime via the weighted histogram
      analysis method, efficient convergence can be robustly ensured, especially for
      the purpose of free energy surface mapping.

PMID- 18624469
TI  - Self-consistent implementation of a nonlocal van der Waals density functional
      with a Gaussian basis set.
AB  - Nearly all common density functional approximations fail to properly describe
      dispersion interactions responsible for binding in van der Waals complexes.
      Empirical corrections can fix some of the failures but cannot fully grasp the
      complex physics and may not be reliable for systems dissimilar to the fitting
      set. In contrast, the recently proposed nonlocal van der Waals density functional
      (vdW-DF) was derived from first principles, describes dispersion interactions in
      a seamless fashion, and yields the correct asymptotics. Implementation of this
      functional is somewhat cumbersome: Nonlocal dependence on the electron density
      requires numerical double integration over the space variables and functional
      derivatives are nontrivial. This paper shows how vdW-DF can be implemented self
      consistently with Gaussian basis functions. The gradients of the energy with
      respect to nuclear displacements have also been derived and coded, enabling
      efficient geometry optimizations. We test the vdW-DF correlation functional in
      combination with several exchange approximations. We also study the sensitivity
      of the method to the basis set size and to the quality of the numerical
      quadrature grid. For weakly interacting systems, acceptable accuracy in semilocal
      exchange is achieved only with fine grids, whereas for nonlocal vdW-DF
      correlation even rather coarse grids are sufficient. The current version of vdW
      DF is not well suited for pairing with Hartree-Fock exchange, leading to
      considerable overbinding.

PMID- 18624470
TI  - Molecular dynamics in the isothermal-isobaric ensemble: the requirement of a
      "shell" molecule. III. Discontinuous potentials.
AB  - Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we
      present a new method for deriving the collisions dynamics for particles that
      interact via discontinuous potentials. By invoking the conservation of the
      extended Hamiltonian, we generate molecular dynamics (MD) algorithms for
      simulating the hard-sphere and square-well fluids within the isothermal-isobaric
      (NpT) ensemble. Consistent with the recent rigorous reformulation of the NpT
      ensemble partition function, the equations of motion impose a constant external
      pressure via the introduction of a shell particle of known mass [M. J. Uline and
      D. S. Corti, J. Chem. Phys. 123, 164101 (2005); 123, 164102 (2005)], which serves
      to define uniquely the volume of the system. The particles are also connected to
      a temperature reservoir through the use of a chain of Nose-Hoover thermostats,
      the properties of which are not affected by a hard-sphere or square-well
      collision. By using the Liouville operator formalism and the Trotter expansion
      theorem to integrate the equations of motion, the update of the thermostat
      variables can be decoupled from the update of the positions of the particles and
      the momentum changes upon a collision. Hence, once the appropriate collision
      dynamics for the isobaric-isenthalpic (NpH) equations of motion is known, the
      adaptation of the algorithm to the NpT ensemble is straightforward. Results of MD
      simulations for the pure component square-well fluid are presented and serve to
      validate our algorithm. Finally, since the mass of the shell particle is known,
      the system itself, and not a piston of arbitrary mass, controls the time scales
      for internal pressure and volume fluctuations. We therefore consider the
      influence of the shell particle algorithm on the dynamics of the square-well
      fluid.

PMID- 18624471
TI  - Piris natural orbital functional study of the dissociation of the radical helium
      dimer.
AB  - We have investigated the dissociation behavior of the radical helium dimer He(2)
      (+) using the Piris natural orbital functional (PNOF). This system is
      particularly challenging to be described by standard density functionals. The
      restricted open formulation of the PNOF-2, as well as the PNOF-2 energy plus the
      extended Koopmans' vertical ionization potential calculations of the neutral
      helium dimer, have been tested for calculating the ground-state energies of He(2)
      (+) as a function of the internuclear distance. For comparison, we present the
      dissociation curve obtained with the diffusion Monte Carlo method. The
      dissociation energies, equilibrium bond lengths, and rovibrational levels are
      reported. The obtained potential energy curves indicate that PNOF-2 yields a
      correct and accurate dissociation behavior for the helium radical dimer.

PMID- 18624472
TI  - Daubechies wavelets as a basis set for density functional pseudopotential
      calculations.
AB  - Daubechies wavelets are a powerful systematic basis set for electronic structure
      calculations because they are orthogonal and localized both in real and Fourier
      space. We describe in detail how this basis set can be used to obtain a highly
      efficient and accurate method for density functional electronic structure
      calculations. An implementation of this method is available in the ABINIT free
      software package. This code shows high systematic convergence properties, very
      good performances, and an excellent efficiency for parallel calculations.

PMID- 18624473
TI  - Self-interaction correction and the optimized effective potential.
AB  - Self-interaction is one of the most substantial problems in present-day density
      functional theory. A widely used approach to overcome this problem is the self
      interaction correction proposed by Perdew and Zunger. However, the thus given
      functional not only depends on the orbitals explicitly but is also variant under
      unitary transformation of the orbitals. In this manuscript, we present a
      generalized version of the optimized effective potential equation which is able
      to deal with both problems in one go. Calculations for molecules exemplify the
      approach.

PMID- 18624474
TI  - Theoretical study of one-photon and two-photon absorption properties of perylene
      tetracarboxylic derivatives.
AB  - The geometrical structure, electronic structure, one-photon absorption (OPA) and
      two-photon absorption (TPA) properties of the perylene tetracarboxylic
      derivatives (PTCDs) were studied theoretically by using density functional theory
      (DFT) and Zerner's intermediate neglect of differential overlap (ZINDO) methods.
      The results revealed that increasing the number of naphthalene nucleus, extending
      the conjugated length on long axis, increasing the strength of donor group on
      lateral side, decreasing the DeltaE(H-L) (energy gap between the highest occupied
      orbital and the lowest unoccupied orbital) and keeping the conjugation effect and
      inductive effect along the same molecular axis are the efficient ways to enlarge
      TPA cross section of PTCDs compounds. The results that PTCDs compounds exhibited
      extremely large TPA cross section of around 800-1100 nm (near infrared region)
      shed light into the significance of the PTCDs compounds for applications in TPA
      labeling materials in vivo.

PMID- 18624475
TI  - Mixed quantum/classical investigation of the photodissociation of NH3(A) and a
      practical method for maintaining zero-point energy in classical trajectories.
AB  - The photodissociation dynamics of ammonia upon excitation of the out-of-plane
      bending mode (mode nu(2) with n(2)=0,[ellipsis (horizontal)],6 quanta of
      vibration) in the A electronic state is investigated by means of several mixed
      quantum/classical methods, and the calculated final-state properties are compared
      to experiments. Five mixed quantum/classical methods are tested: one mean-field
      approach (the coherent switching with decay of mixing method), two surface
      hopping methods [the fewest switches with time uncertainty (FSTU) and FSTU with
      stochastic decay (FSTU/SD) methods], and two surface-hopping methods with zero
      point energy (ZPE) maintenance [the FSTUSD+trajectory projection onto ZPE orbit
      (TRAPZ) and FSTUSD+minimal TRAPZ (mTRAPZ) methods]. We found a qualitative
      difference between final NH(2) internal energy distributions obtained for n(2)=0
      and n(2)>1, as observed in experiments. Distributions obtained for n(2)=1 present
      an intermediate behavior between distributions obtained for smaller and larger
      n(2) values. The dynamics is found to be highly electronically nonadiabatic with
      all these methods. NH(2) internal energy distributions may have a negative energy
      tail when the ZPE is not maintained throughout the dynamics. The original TRAPZ
      method was designed to maintain ZPE in classical trajectories, but we find that
      it leads to unphysically high internal vibrational energies. The mTRAPZ method,
      which is new in this work and provides a general method for maintaining ZPE in
      either single-surface or multisurface trajectories, does not lead to unphysical
      results and is much less time consuming. The effect of maintaining ZPE in mixed
      quantum/classical dynamics is discussed in terms of agreement with experimental
      findings. The dynamics for n(2)=0 and n(2)=6 are also analyzed to reveal details
      not available from experiment, in particular, the time required for quenching of
      electronic excitation and the adiabatic energy gap and geometry at the time of
      quenching.

PMID- 18624476
TI  - Energy-dependent dynamics of large-DeltaE collisions: highly vibrationally
      excited azulene (E=20 390 and 38 580 cm(-1)) with CO2.
AB  - We report the energy dependence of strong collisions of CO(2) with highly
      vibrationally excited azulene for two initial energies, E=20 390 and 38 580 cm(
      1). These studies show that both the distribution of transferred energy and the
      energy transfer rates are sensitive to the azulene energy. Highly excited azulene
      was prepared in separate studies by absorption of pulsed excitation at lambda=532
      or 266 nm, followed by rapid radiationless decay from S(1) or S(4) to
      vibrationally excited levels of the ground electronic state. The appearance of
      scattered CO(2) (00(0)0) molecules with E(rot)>1000 cm(-1) was monitored by high
      resolution transient IR absorption at lambda=4.3 mum. The average rotational and
      translational energies of the scattered CO(2) molecules double when the azulene
      energy is increased by a factor of 2. The rate of energy transfer in strong
      collisions increases by nearly a factor of 4 when the azulene energy is doubled.
      The energy transfer probability distribution function for DeltaE>3000 cm(-1) at
      each initial energy is an exponential decay with curvature that correlates with
      the energy dependence of the state density, in excellent agreement with
      predictions from GRETCHEN, a model based on Fermi's golden rule to describe
      collisional quenching of highly excited molecules.

PMID- 18624477
TI  - Do ionic and hydrophobic probes sense similar microenvironment in Triton X-100
      nonionic reverse micelles?
AB  - Rotational diffusion of two structurally similar ionic probes, rhodamine 110 and
      fluorescein, has been examined in nonionic reverse micellar system of Triton X
      100/benzene-n-hexane/water as a function of mole ratio of the water to
      surfactant, W. This study has been undertaken to find out whether ionic and
      hydrophobic probes experience similar microenvironment in these reverse micelles.
      Experimental results indicate that, from W=0 to 3, the average reorientation
      time, which is a measure of the microviscosity experienced by the probe molecule,
      increases by 90% and 40% for rhodamine 110 and fluorescein, respectively, and
      from W=3 to 8, it decreases by 20% for both the probes. The increase in the
      average reorientation time with W has been rationalized on the basis of the
      flexible oxyethylene chains of the TX-100 surfactant being hydrogen bonded by the
      water molecules, which makes the core region less fluid. However, once the
      hydration of the oxyethylene chains is complete, further addition of water
      results in formation of water droplet; which renders the micelle-water interface
      in the core region less compact leading to a marginal decrease in the average
      reorientation time of the probe molecules. These explanations are consistent with
      the location of the probes and the structure of the Triton X-100/benzene
      hexane/water reverse micelles. To compare how the microenvironment experienced by
      these ionic probes is different from the hydrophobic ones, results from our
      earlier work [J. Phys. Chem. B 108, 7944 (2004)] have been considered. Such a
      comparison revealed that both ionic and hydrophobic probes experience similar
      microenvironment in these reverse micelles until the hydration of the oxyethylene
      chains is complete. In case of hydrophobic probes, however, the onset of water
      droplet formation does not alter their microenvironment, which is due to their
      location in the reverse micellar cores.

PMID- 18624478
TI  - Shear thinning and shear dilatancy of liquid n-hexadecane via equilibrium and
      nonequilibrium molecular dynamics simulations: Temperature, pressure, and density
      effects.
AB  - Equilibrium and nonequilibrium molecular dynamics (MD) simulations have been
      performed in both isochoric-isothermal (NVT) and isobaric-isothermal (NPT)
      ensemble systems. Under steady state shearing conditions, thermodynamic states
      and rheological properties of liquid n-hexadecane molecules have been studied.
      Between equilibrium and nonequilibrium states, it is important to understand how
      shear rates (gamma) affect the thermodynamic state variables of temperature,
      pressure, and density. At lower shear rates of gamma<1 x 10(11) s(-1), the
      relationships between the thermodynamic variables at nonequilibrium states
      closely approximate those at equilibrium states, namely, the liquid is very near
      its Newtonian fluid regime. Conversely, at extreme shear rates of gamma>1 x
      10(11) s(-1), specific behavior of shear dilatancy is observed in the variations
      of nonequilibrium thermodynamic states. Significantly, by analyzing the effects
      of changes in temperature, pressure, and density on shear flow system, we report
      a variety of rheological properties including the shear thinning relationship
      between viscosity and shear rate, zero-shear-rate viscosity, rotational
      relaxation time, and critical shear rate. In addition, the flow activation energy
      and the pressure-viscosity coefficient determined through Arrhenius and Barus
      equations acceptably agree with the related experimental and MD simulation
      results.

PMID- 18624479
TI  - Metal clusters that freeze into high energy geometries.
AB  - Heat capacities measured for isolated aluminum clusters show peaks due to
      melting. For some clusters with around 60 and 80 atoms there is a dip in the heat
      capacities at a slightly lower temperature than the peak. The dips have been
      attributed to structural transitions. Here we report studies where the clusters
      are annealed before the heat capacity is measured. The dips disappear for some
      clusters, but in many cases they persist, even when the clusters are annealed to
      well above their melting temperature. This indicates that the dips do not result
      from badly formed clusters generated during cluster growth, as originally
      suggested. We develop a simple kinetic model of melting and freezing in a system
      consisting of one liquidlike and two solidlike states with different melting
      temperatures and latent heats. Using this model we are able to reproduce the
      experimental results including the dependence on the annealing conditions. The
      dips result from freezing into a high energy geometry and then annealing into the
      thermodynamically preferred solid. The thermodynamically preferred solid has the
      higher freezing temperature. However, the liquid can bypass freezing into the
      thermodynamically preferred solid (at high cooling rates) if the higher energy
      geometry has a larger freezing rate.

PMID- 18624480
TI  - Selective polarization transfer using a single rf field.
AB  - NMR is a popular and mature technique used in fields as diverse as chemistry,
      biology, or material science. One reason for this versatility lies in its ability
      to correlate the nuclei that are present in one molecule to another. This
      provides the researcher with correlation maps allowing for studies of the
      molecules at an atomic level. Selective experiments allow isolation of one such
      correlation to focus on spins of interest. This leads to a savings in precious
      experimental time by reducing the dimension of the experiment, which in turn may
      enable one to record more elaborate experiments that would otherwise not be
      amenable within reasonable acquisition times. Here, we present an alternative
      method to selectively transfer magnetization using a single rf field. This
      technique, which we call single field polarization transfer, allows to obtain
      longitudinal two-spin order of two scalar-coupled spins when only one of them is
      irradiated. The method is easy to implement and does not depend on stringent
      conditions, such as Hartmann-Hahn matching for selective cross-polarization
      transfers or very long inversion pulses and identification of coupling satellites
      in selective population inversion experiments.

PMID- 18624481
TI  - The photophysics of all-trans polyenes from ttbP5, a nonphotolabile pentaene.
AB  - The all-trans pentaene, 3,12-di(tert-butyl)-2,2,13,13-tetramethyl-3,5,7,9,11
      tetradecapentaene (ttbP5) fluoresces in two different regions of the visible
      spectrum. It produces an extremely weak emission in the gas phase that can also
      be detected in the condensed phase; such an emission exhibits a negligible Stokes
      shift with respect to the 1Ag-->1Bu absorption transition and can in principle be
      assigned to the 1Bu-->1Ag emission of the compound. ttbP5 also exhibits a second
      fluorescence emission at approximately 520 nm in both the gas phase and the
      condensed phase. The emission in the condensed phase increases in strength and
      structure, with no change in spectral position, as the solvent viscosity
      increases by effect of the solution temperature being lowered. The spectral
      behavior of this pentaene (ttbP5) is different enough from that reported [J.
      Catalan et al., J. Chem. Phys. 128, 104504 (2008)] for its tetraene counterpart
      (ttbP4) to warrant a separate analysis in order to facilitate a better
      understanding of the way the photophysics of these polyenes changes as their
      chain is lengthened.

PMID- 18624482
TI  - The H2O2+OH-->HO2+H2O reaction in aqueous solution from a charge-dependent
      continuum model of solvation.
AB  - We applied our recently developed protocol of the conductorlike continuum model
      of solvation to describe the title reaction in aqueous solution. The model has
      the unique feature of the molecular cavity being dependent on the atomic charges
      in the solute and can be extended naturally to transition states and reaction
      pathways. It was used to calculate the reaction energetics and reaction rate in
      solution for the title reaction. The rate of reaction calculated using canonical
      variational transition state theory in the context of the equilibrium solvation
      path approximation, and including correction for tunneling through the small
      curvature approximation, was found to be 3.6 x 10(6) M(-1) s(-1), significantly
      slower than in the gas phase in accord with experiment. These results suggest
      that the present protocol of the conductorlike continuum model of solvation with
      the charge-dependent cavity definition captures qualitatively and quantitatively
      the solvation effects at transition states and allows for quantitative estimates
      of reaction rates in solutions.

PMID- 18624483
TI  - Frequency autocorrelation function of stochastically fluctuating fields caused by
      specific magnetic field inhomogeneities.
AB  - Signal formation in NMR is due to incoherent dephasing of nuclear spins. Of
      particular practical importance is the situation of nuclear spins undergoing
      independent stochastic motion in inhomogeneous local magnetic fields, e.g.,
      created by magnetized objects. Since it was demonstrated recently that the
      frequency correlation function of nuclear spins can be measured directly, a
      theoretical analysis of such functions is of interest. Here, we provide a
      numerically exact analysis of that correlation function for the inhomogeneous
      fields around two particular geometries: cylinders and spheres. The functional
      form exhibits three regimes: after an initial transient, there is an algebraic
      regime with a t(-d/2) time dependence (d being the space dimension), followed by
      an exponential cutoff due to microscopic system size effects. The main parameter
      controlling the range of the individual regimes is the volume fraction of the
      magnetized objects. In addition to our numerical analysis, which is based on
      eigenfunction expansions, we provide analytical results and approximations based
      on the generalized moment expansion.

PMID- 18624484
TI  - Noise-induced order in the chaos of the Belousov-Zhabotinsky reaction.
AB  - Noise can stabilize a metastable state in such a way that the system remains in
      this state for a longer time than in the absence of noise. When this phenomenon
      is observed in chaos, it is called "noise-induced order." We have experimentally
      detected noise-induced order in the Belousov-Zhabotinsky reaction. That is, when
      noise is added to the chaos with the flow rate near the period-three oscillation,
      a decrease of the maximum Lyapunov exponent and a convergence of the Fourier
      spectrum are observed. Moreover, the analysis on the one-dimensional return map
      reveals that noise-induced order is caused by the convergence of the chaotic
      trajectory into the laminar region.

PMID- 18624486
TI  - Virial series for fluids of hard hyperspheres in odd dimensions.
AB  - A recently derived method [R. D. Rohrmann and A. Santos, Phys. Rev. E 76, 051202
      (2007)] to obtain the exact solution of the Percus-Yevick equation for a fluid of
      hard spheres in (odd) d dimensions is used to investigate the convergence
      properties of the resulting virial series. This is done both for the virial and
      compressibility routes, in which the virial coefficients B(j) are expressed in
      terms of the solution of a set of (d-1)/2 coupled algebraic equations which
      become nonlinear for d>/=5. Results have been derived up to d=13. A confirmation
      of the alternating character of the series for d>/=5, due to the existence of a
      branch point on the negative real axis, is found and the radius of convergence is
      explicitly determined for each dimension. The resulting scaled density per
      dimension 2eta(1/d), where eta is the packing fraction, is wholly consistent with
      the limiting value of 1 for d-->infinity. Finally, the values for B(j) predicted
      by the virial and compressibility routes in the Percus-Yevick approximation are
      compared with the known exact values [N. Clisby and B. M. McCoy, J. Stat. Phys.
      122, 15 (2006)].

PMID- 18624485
TI  - Variable atomic radii for continuum-solvent electrostatics calculation.
AB  - We have developed a method to improve the description of solute cavity defined by
      the interlocking-sphere model for continuum-solvent electrostatics calculations.
      Many models choose atomic radii from a finite set of atom types or uses an even
      smaller set developed by Bondi [J. Phys. Chem. 68, 441 (1964)]. The new model
      presented here allowed each atom to adapt its radius according to its chemical
      environment. This was achieved by first approximating the electron density of a
      molecule by a superposition of atom-centered spherical Gaussian functions. The
      parameters of the Gaussian functions were then determined by optimizing a
      function that minimized the difference between the properties from the model and
      those from ab initio quantum calculations. These properties included the
      electrostatics potential on molecular surface and the electron density within the
      core of each atom. The size of each atom was then determined by finding the
      radius at which the electron density associated with the atom fell to a prechosen
      value. This value was different for different chemical elements and was chosen
      such that the averaged radius for each chemical element in a training set of
      molecules matched its Bondi radius. Thus, our model utilized only a few
      adjustable parameters-the above density cutoff values for different chemical
      elements-but had the flexibility of allowing every atom to adapt its radius
      according to its chemical environment. This variable-radii model gave better
      solvation energy for 31 small neutral molecules than the Bondi radii did,
      especially for a quantum mechanics/Poisson-Boltzmann approach we developed
      earlier. The improvement was most significant for molecules with large dipole
      moment. Future directions for further improvement are also discussed.

PMID- 18624487
TI  - Thermodynamic response functions of fluids: a microscopic approach based on NpT
      Monte Carlo.
AB  - On the basis of NpT Monte Carlo simulations, a detailed analysis on the
      microscopic origins of some specific features of thermodynamic response functions
      of fluids is performed. Specifically, the residual isobaric heat capacity C(p)
      (res), the isobaric thermal expansivity alpha(p), and the isothermal
      compressibility kappa(T) for Lennard-Jones methane and optimized potential for
      liquid simulations (OPLS) methanol have been determined via standard techniques.
      For the former, data along the liquid, gas, and supercritical regions are
      presented, while a wide temperature range at a single supercritical pressure is
      covered for the latter. They have been obtained by computing the various pairwise
      fluctuations contributing to each property. Attention is mainly focused on
      isothermal and isobaric maxima found for both C(p) (res) and alpha(p), which have
      been rationalized at a molecular level using qualitative arguments. It is
      encountered that maxima emerge as a natural consequence of the destruction of
      fluid structure as temperature is increased or as pressure is decreased. The
      results for Lennard-Jones methane reveal the competition of energetic and
      volumetric effects, while those for OPLS methanol evidence that hydrogen-bonding
      is dominant as energetic effects are concerned. Further discussion on previous
      results and alternative approaches using equations of state as well as on closely
      related topics such as "maxima and critical phenomena" is included.

PMID- 18624488
TI  - Very strong hydrogen bonds in a bent chain structure of fluorohydrogenate anions
      in liquid Cs(FH)2.3F.
AB  - The structure of liquid Cs(FH)(2.3)F was revealed using a combination of high
      energy x-ray and neutron diffraction measurements. We found that the strongest
      intermolecular H-F hydrogen bonds at an average distance of 1.36 A are
      accompanied by the formation of a high degree of bending of the oligomer chain in
      the melt, with [angle]FHF=150 degrees . A reverse Monte Carlo simulation showed
      that the average number of atoms per chain is 4.4. A detailed chain analysis of
      the atomic configuration revealed that (FH)(2)F(-) oligomer chains are the major
      entities in the liquid, and asymmetrical FHF(-) are formed owing to the strong H
      F hydrogen bonds. The results suggest that an average of one or two HF molecules
      bond to each of the 11 fluorine atoms surrounding a cesium ion.

PMID- 18624489
TI  - Self-diffusion in molecular liquids: medium-chain n-alkanes and coenzyme Q10
      studied by quasielastic neutron scattering.
AB  - A systematic time-of-flight quasielastic neutron scattering (TOF-QENS) study on
      diffusion of n-alkanes in a melt is presented for the first time. As another
      example of a medium-chain molecule, coenzyme Q(10) is investigated in the same
      way. The data were evaluated both in the frequency and in the time domain. TOF
      QENS data can be satisfactorily described by different models, and it turned out
      that the determined diffusion coefficients are largely independent of the applied
      model. The derived diffusion coefficients are compared with values measured by
      pulsed-field gradient nuclear magnetic resonance (PFG-NMR). With increasing chain
      length, an increasing difference between the TOF-QENS diffusion coefficient and
      the PFG-NMR diffusion coefficient is observed. This discrepancy in the diffusion
      coefficients is most likely due to a change of the diffusion mechanism on a
      nanometer length scale for molecules of medium-chain length.

PMID- 18624490
TI  - Luminescence from 3,4,9,10-perylenetetracarboxylic dianhydride on Ag(111) surface
      excited by tunneling electrons in scanning tunneling microscopy.
AB  - The electronic excitations induced with tunneling electrons into adlayers of
      3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) on Ag(111) have been
      investigated by in situ fluorescence spectroscopy in scanning tunneling
      microscopy (STM). A minute area of the surface is excited by an electron
      tunneling process in STM. Fluorescence spectra strongly depend on the coverage of
      PTCDA on Ag(111). The adsorption of the first PTCDA layer quenches the intrinsic
      surface plasmon originated from the clean Ag(111). When the second layer is
      formed, fluorescence spectra are dominated by the signals from PTCDA, which are
      interpreted as the radiative decay from the manifold of first singlet excited
      state (S(1)) of adsorbed PTCDA. The fluorescence of PTCDA is independent of the
      bias polarity. In addition, the fluorescence excitation spectrum agrees with that
      by optical excitation. Both results indicate that S(1) is directly excited by the
      inelastic impact scattering of electrons tunneling within the PTCDA adlayer.

PMID- 18624491
TI  - The thickness of a liquid layer on the free surface of ice as obtained from
      computer simulation.
AB  - Molecular dynamic simulations were performed for ice I(h) with a free surface by
      using four water models, SPC/E, TIP4P, TIP4P/Ice, and TIP4P/2005. The behavior of
      the basal plane, the primary prismatic plane, and of the secondary prismatic
      plane when exposed to vacuum was analyzed. We observe the formation of a thin
      liquid layer at the ice surface at temperatures below the melting point for all
      models and the three planes considered. For a given plane it was found that the
      thickness of a liquid layer was similar for different water models, when the
      comparison is made at the same undercooling with respect to the melting point of
      the model. The liquid layer thickness is found to increase with temperature. For
      a fixed temperature it was found that the thickness of the liquid layer decreases
      in the following order: the basal plane, the primary prismatic plane, and the
      secondary prismatic plane. For the TIP4P/Ice model, a model reproducing the
      experimental value of the melting temperature of ice, the first clear indication
      of the formation of a liquid layer, appears at about -100 degrees C for the basal
      plane, at about -80 degrees C for the primary prismatic plane, and at about -70
      degrees C for the secondary prismatic plane.

PMID- 18624492
TI  - Fluctuation-induced interactions between dielectrics in general geometries.
AB  - We study thermal Casimir and quantum nonretarded Lifshitz interactions between
      dielectrics in general geometries. We map the calculation of the classical
      partition function onto a determinant, which we discretize and evaluate with the
      help of Cholesky factorization. The quantum partition function is treated by path
      integral quantization of a set of interacting dipoles and reduces to a product of
      determinants. We compare the approximations of pairwise additivity and proximity
      force with our numerical methods. We propose a "factorization approximation" that
      gives rather good numerical results in the geometries that we study.

PMID- 18624493
TI  - Modulation of surface reactivity via electron confinement in metal quantum well
      films: O2 adsorption on PbSi(111).
AB  - Pb quantum well films with atomic-scale uniformity in thickness over macroscopic
      areas were prepared on Si(111)-7x7 surfaces. As a probe molecule, O(2) was used
      to explore the effect of electron confinement in the metal films on the surface
      reactivity. X-ray photoelectron spectroscopy results showed clear oscillations of
      oxygen adsorption and Pb oxidation with the thickness of the Pb films. The higher
      reactivity to O(2) on the films with 23 and 25 ML Pb has been attributed to their
      highest occupied quantum well states being close to the Fermi level (E(F)) and
      the high density of the electron states at E(F) (DOS-E(F)), as evidenced by the
      corresponding ultraviolet photoelectron spectroscopy. A dominant role of DOS-E(F)
      was suggested to explain the quantum modulation of surface reactivity in metal
      quantum well films.

PMID- 18624494
TI  - Phase-field modeling of solute precipitation and dissolution.
AB  - A phase-field approach to the dynamics of liquid-solid interfaces that evolve due
      to precipitation and/or dissolution is presented. For the purpose of illustration
      and comparison with other methods, phase-field simulations were carried out
      assuming first order reaction (dissolution/precipitation) kinetics. In contrast
      to solidification processes controlled by a temperature field that is continuous
      across the solid/liquid interface (with a discontinuous temperature gradient),
      precipitation/dissolution is controlled by a solute concentration field that is
      discontinuous at the solid/liquid interface. The sharp-interface asymptotic
      analysis of the phase-field equations for solidification [A. Karma and W.-J.
      Rappel, Phys. Rev. E 57, 4323 (1998)] has been modified for
      precipitation/dissolution processes to demonstrate that the phase-field equations
      converge to the proper sharp-interface limit. The mathematical model has been
      validated for a one-dimensional precipitation/dissolution problem by comparison
      with the analytical solution.

PMID- 18624495
TI  - Optical excitations of defects in realistic nanoscale silica clusters: comparing
      the performance of density functional theory using hybrid functionals with
      correlated wavefunction methods.
AB  - Optical excitations of low energy silica (SiO(2))(4) clusters obtained by global
      optimization, as opposed to constructed by hand, are studied using a range of
      theoretical methods. By focusing on the lowest energy silica clusters we hope to
      capture at least some of the characteristic ways by which the dry surfaces of
      silica nanosystems preferentially terminate. Employing the six lowest energy
      (SiO(2))(4) cluster isomers, we show that they exhibit a surprisingly wide range
      of geometries, defects, and associated optical excitations. Some of the clusters
      show excitations localized on isolated defects, which are known from previous
      studies using hydrogen-terminated versions of the defect in question. Other
      clusters, however, exhibit novel charge-transfer excitations in which an electron
      transfers between two spatially separated defects. In these cases, because of the
      inherent proximity of the constituent defects due to the small cluster
      dimensions, the excitation spectrum is found to be very different from that of
      the same defects in isolation. Excitation spectra of all clusters were calculated
      using time-dependent density functional theory (TD-DFT) and delta-SCF DFT
      (DeltaDFT) methods employing two different hybrid density functionals (B3LYP and
      BB1K) differing essentially in the amount of incorporated Hartree-Fock-like
      exchange (HFLE). In all cases the results were compared with CASPT2 calculated
      values which are taken as a benchmark standard. In line with previous work, the
      spatially localized excitations are found to be well described by TD-DFT/B3LYP
      but which gives excitation energies that are significantly underestimated in the
      case of the charge-transfer excitations. The TD-DFT/BB1K combination in contrast
      is found to give generally good excitation energies for the lowest excited states
      of both localized and charge-transfer excitations. Finally, our calculations
      suggest that the increased quality of the predicted excitation spectra by adding
      larger amounts of HFLE is mainly due to an increased localization of the excited
      state associated with the elimination of spurious self-interaction inherent to
      (semi-)local DFT functionals.

PMID- 18624496
TI  - Appearance of the bulk motif in Al clusters.
AB  - We have performed an unbiased search for the lowest-energy structures of medium
      sized aluminum clusters Al(n) (n=19-26) using a genetic algorithm (GA) coupled
      with a tight-binding interatomic potential. Structural candidates obtained from
      our GA search were further optimized using density functional theory. It is found
      that the double icosahedron is not the most stable structure for Al(19) but
      serves as the core for Al(20) and Al(21). The lowest-energy structures of Al(n)
      are found to undergo a transition to an aluminum bulk motif above Al(23). In
      particular, the lowest-energy structure of Al(26) is almost a fragment of the
      bulk face-centered-cubic crystal except for the stacking fault at the bottom
      layer. Anion clusters were also studied.

PMID- 18624497
TI  - Nanodrop on a nanorough solid surface: density functional theory considerations.
AB  - The density distributions and contact angles of liquid nanodrops on nanorough
      solid surfaces are determined on the basis of a nonlocal density functional
      theory. Two kinds of roughness, chemical and physical, are examined. The former
      considers the substrate as a sequence of two kinds of semi-infinite vertical
      plates of equal thicknesses but of different natures with different strengths for
      the liquid-solid interactions. The physical roughness involves an ordered set of
      pillars on a flat homogeneous surface. Both hydrophobic and hydrophilic surfaces
      were considered. For the chemical roughness, the contact angle which the drop
      makes with the flat surface increases when the strength of the liquid-solid
      interaction for one kind of plates decreases with respect to the fixed value of
      the other kind of plates. Such a behavior is in agreement with the Cassie-Baxter
      expression derived from macroscopic considerations. For the physical roughness on
      a hydrophobic surface, the contact angle which a drop makes with the plane
      containing the tops of the pillars increases with increasing roughness. Such a
      behavior is consistent with the Wenzel formula developed for macroscopic drops.
      For hydrophilic surfaces, as the roughness increases the contact angle first
      increases, in contradiction with the Wenzel formula, which predicts for
      hydrophilic surfaces a decrease of the contact angle with increasing roughness.
      However, a further increase in roughness changes nonmonotonously the contact
      angle, and at some roughness, the drop disappears and only a liquid film is
      present on the surface. It was also found that the contact angle has a periodic
      dependence on the volume of the drop.

PMID- 18624498
TI  - Hydrogen peroxide formation following the vacuum ultraviolet photodissociation of
      water ice films at 90 K.
AB  - The production of gaseous OH radicals from the 300-350 nm photodissociation of
      H(2)O(2) that was photolytically produced on a water ice surface following the
      157 nm photolysis of water ice at 90 K was directly monitored using resonance
      enhanced multiphoton ionization. The translational energy distribution estimated
      by the time-of-flight spectrum of the OH products is represented by a Maxwell
      Boltzmann energy distribution with a translational temperature of 3750+/-250 K.
      The rotational temperature was estimated by a spectral simulation to be 225+/-25
      K. Surface defects produced by HCl deposition on the water ice contributed to the
      higher production rate of H(2)O(2) in the 157 nm photoirradiation of water ice
      while surface coverage caused by CD(3)OH deposition decreased the H(2)O(2)
      production rate.

PMID- 18624499
TI  - Theory of the observed ultralow friction between sliding polyelectrolyte brushes.
AB  - It is shown using a method based on a modified version of the mean field theory
      of Miklavic and Marcelja [J. Phys. Chem. 92, 6718 (1988)] that it should be
      possible for osmotic pressure due to the counterions associated with the two
      polyelectrolyte polymer brush coated surfaces to support a reasonable load (i.e.,
      about 10(6) Pa) with the brushes held sufficiently far apart to prevent
      entanglement of polymers belonging to the two brushes, thus avoiding what is
      believed to be the dominant mechanisms for static and dry friction.

PMID- 18624500
TI  - Using free energy perturbation to predict effects of changing force field
      parameters on computed conformational equilibriums of peptides.
AB  - We propose a method that may allow data about the conformational equilibriums of
      peptides to enter the parameter calibration phase in force field developments.
      The method combines free energy perturbation with techniques for extensive
      sampling in the conformational space. It predicts shifts in computed
      conformational equilibriums in response to separate or combined perturbations of
      force field parameters. As an example we considered a force field associated with
      an implicit solvent model. We considered two different approaches to define
      conformational states of four peptides. One is based on reaction coordinates and
      two-dimensional free energy surfaces. The other is based on the clustering
      analysis of sampled conformations. Effects of perturbing various model parameters
      on the equilibriums between nativelike states with other conformational states
      were considered. For one type of perturbation predicted to have consistent
      effects on different peptides, the predictions have been verified by actual
      simulations using a perturbed model.

PMID- 18624501
TI  - Dipole-induced self-assembly of helical beta-peptides.
AB  - In this work, the interactions between beta-peptides are investigated for helix
      forming peptides using molecular simulation. The role of electrostatic
      interactions in the self-assembly of these peptides is studied by calculating the
      dipole moment of various 14-helical beta-peptides using molecular dynamics
      simulations. The stability of a beta-peptide that is known to form a liquid
      crystalline phase is determined by calculating the potential of mean force using
      the expanded ensemble density of states method. This peptide is found to form a
      mechanically stable 14-helix in an implicit solvent model. The interaction
      between two of these peptides is examined by calculating the potential of mean
      force between the two peptides in implicit solvent. The peptides are shown to
      favorably associate in an end-to-end manner, driven largely by dipolar
      interactions. In order to understand the possible structures that form when many
      peptides interact in solution, a coarse-grained model is developed. Brownian
      dynamics simulations of the coarse-grained model at intermediate concentrations
      (1-50 mM) are performed, and the aggregation behavior is understood by
      calculating the diffusivity and the radial distribution function. An analysis of
      the resultant structures reveals that the coarse-grained model of the peptide
      leads to the formation of spherical clusters.

PMID- 18624502
TI  - Electrostatic similarity of proteins: application of three dimensional spherical
      harmonic decomposition.
AB  - We present a method for describing and comparing global electrostatic properties
      of biomolecules based on the spherical harmonic decomposition of electrostatic
      potential data. Unlike other approaches our method does not require any prior
      three dimensional structural alignment. The electrostatic potential, given as a
      volumetric data set from a numerical solution of the Poisson or Poisson-Boltzmann
      equation, is represented with descriptors that are rotation invariant. The method
      can be applied to large and structurally diverse sets of biomolecules enabling to
      cluster them according to their electrostatic features.

PMID- 18624503
TI  - Sensitivity amplification in the phosphorylation-dephosphorylation cycle:
      nonequilibrium steady states, chemical master equation, and temporal
      cooperativity.
AB  - A new type of cooperativity termed temporal cooperativity [Biophys. Chem. 105,
      585 (2003); Annu. Rev. Phys. Chem. 58, 113 (2007)] emerges in the signal
      transduction module of phosphorylation-dephosphorylation cycle (PdPC). It
      utilizes multiple kinetic cycles in time, in contrast to allosteric cooperativity
      that utilizes multiple subunits in a protein. In the present paper, we thoroughly
      investigate both the deterministic (microscopic) and stochastic (mesoscopic)
      models and focus on the identification of the source of temporal cooperativity
      via comparing with allosteric cooperativity. A thermodynamic analysis confirms
      again the claim that the chemical equilibrium state exists if and only if the
      phosphorylation potential DeltaG=0, in which case the amplification of
      sensitivity is completely abolished. Then we provide comprehensive theoretical
      and numerical analysis with the first-order and zero-order assumptions in PdPC,
      respectively. Furthermore, it is interestingly found that the underlying
      mathematics of temporal cooperativity and allosteric cooperativity are
      equivalent, and both of them can be expressed by "dissociation constants," which
      also characterizes the essential differences between the simple and
      ultrasensitive PdPC switches. Nevertheless, the degree of allosteric
      cooperativity is restricted by the total number of sites in a single enzyme
      molecule that cannot be freely regulated, while temporal cooperativity is only
      restricted by the total number of molecules of the target protein that can be
      regulated in a wide range and gives rise to the ultrasensitivity phenomenon.

PMID- 18624504
TI  - Coverage-dependent sticking probability and desorption kinetics of water
      molecules on Rh(111).
AB  - The adsorption and desorption kinetics of water molecules on Rh(111) were
      investigated using temperature programed desorption (TPD). Water molecules on
      Rh(111) show coverage-dependent sticking probability; the initial sticking
      probability is estimated to be 0.46. In the desorption process, a dilute gaslike
      phase and two-dimensional islands of water coexist on the surface. Based on the
      model proposed by Kreuzer and Payne [Surf. Sci.200, L433 (1988)], the apparent
      fractional-order TPD spectra can be interpreted as first-order desorption from
      the coexistence of two phases on which the sticking probabilities are different.
      Based on this, the previous estimation of pre-exponential factors assuming half
      order desorption [A. Beniya et al., J. Chem. Phys.125, 054717 (2006)] should be
      revised.

PMID- 18624505
TI  - Spherical tensor gradient operator method for integral rotation: a simple,
      efficient, and extendable alternative to Slater-Koster tables.
AB  - We present a novel alternative to the use of Slater-Koster tables for the
      efficient rotation and gradient evaluation of two-center integrals used in tight
      binding Hamiltonian models. The method recasts the problem into an exact, yet
      implicit, basis representation through which the properties of the spherical
      tensor gradient operator are exploited. These properties provide a factor of 3 to
      4 speedup in the evaluation of the integral gradients and afford a compact code
      structure that easily extends to high angular momentum without loss in
      efficiency. Thus, the present work is important in improving the performance of
      tight-binding models in molecular dynamics simulations and has particular use for
      methods that require the evaluation of two-center integrals that involve high
      angular momentum basis functions. These advances have a potential impact for the
      design of new tight-binding models that incorporate polarization or transition
      metal basis functions and methods based on electron density fitting of molecular
      fragments.

PMID- 18624509
TI  - Simple Landau model of the R(IV)-R(III)-R(V) rotator phases of alkanes.
AB  - Simple Landau-type free energy function is presented to describe the R(IV)-R(III)
      R(V) rotator phase sequence and the transitions between them. The order
      parameters necessary to describe the above rotator phase transitions are
      identified. Varying the coupling between the order parameters, the R(IV)-R(III)
      and R(III)-R(V) transitions occur. Available experimental results are consistent
      with our model.

PMID- 18624510
TI  - Orientation of dipole molecules and clusters upon adiabatic entry into an
      external field.
AB  - The induced polarization of a beam of polar clusters or molecules passing through
      an electric or magnetic field region differs from the textbook Langevin-Debye
      susceptibility. This distinction, which is important for the interpretation of
      deflection and focusing experiments, arises because instead of acquiring thermal
      equilibrium in the field region, the beam ensemble typically enters the field
      adiabatically, i.e., with a previously fixed distribution of rotational states.
      We discuss the orientation of rigid symmetric top systems with a body-fixed
      electric or magnetic dipole moment. The analytical expression for their
      "adiabatic-entry" orientation is elucidated and compared with exact numerical
      results for a range of parameters. The differences between the polarization of
      thermodynamic and "adiabatic-entry" ensembles of prolate and oblate tops, and of
      symmetric top and linear rotators, are illustrated and identified.

PMID- 18624512
TI  - Accurate calculation of transport properties for organic molecular semiconductors
      with spin-component scaled MP2 and modern density functional theory methods.
AB  - At ambient temperatures, intermolecular hopping of charge carriers dominates the
      field effect mobility and thus the performance of organic molecular
      semiconductors for organic-based electronic devices. We have used a wide variety
      of modern and accurate computational methods to calculate the main parameters
      associated with charge transport, taking oligoacenes, and its derivatives as the
      exemplary organic materials. We tackle the problem from a combined inter- and
      intramolecular approach, in which the parameters are calculated for an isolated
      single molecule concomitantly with the stability of the dimers found in
      experimentally determined crystalline structures. Considering that most of the
      future applications within the field would need a full understanding of the
      transport mechanism, we assess the reliability of the methods to be employed
      according to the nature of the problem. Finally, we perform a computationally
      guided molecular engineering of a new set of materials derived from tetracene
      (rubrene and highly twisted oligoacenes) which allows to robustly anticipate the
      reasons for their expected performance in organic-based electronic devices.

PMID- 18624511
TI  - Bayesian estimates of free energies from nonequilibrium work data in the presence
      of instrument noise.
AB  - The Jarzynski equality and the fluctuation theorem relate equilibrium free energy
      differences to nonequilibrium measurements of the work. These relations extend to
      single-molecule experiments that have probed the finite-time thermodynamics of
      proteins and nucleic acids. The effects of experimental error and instrument
      noise have not been considered previously. Here, we present a Bayesian formalism
      for estimating free energy changes from nonequilibrium work measurements that
      compensates for instrument noise and combines data from multiple driving
      protocols. We reanalyze a recent set of experiments in which a single RNA hairpin
      is unfolded and refolded using optical tweezers at three different rates.
      Interestingly, the fastest and farthest-from-equilibrium measurements contain the
      least instrumental noise and, therefore, provide a more accurate estimate of the
      free energies than a few slow, more noisy, near-equilibrium measurements. The
      methods we propose here will extend the scope of single-molecule experiments;
      they can be used in the analysis of data from measurements with atomic force
      microscopy, optical, and magnetic tweezers.

PMID- 18624513
TI  - Calculating vibrational spectra using modified Shepard interpolated potential
      energy surfaces.
AB  - A potential energy interpolation approach based on modified Shepard interpolation
      and specifically designed for calculation of vibrational states is presented. The
      importance of the choice of coordinates for the rate of convergence is
      demonstrated. Studying the vibrational states of the water molecule as a test
      case, a coordinate system comprised of inverse bond distances and trigonometric
      functions of the bond angle is found to be particularly efficient. Different
      sampling schemes used to locate the reference points in the modified Shepard
      interpolation are investigated. A final scheme is recommended, which allows the
      construction of potential energy surfaces to sub-wave-number accuracy.

PMID- 18624514
TI  - An efficient ring polymer contraction scheme for imaginary time path integral
      simulations.
AB  - A quantum simulation of an imaginary time path integral typically requires around
      n times more computational effort than the corresponding classical simulation,
      where n is the number of ring polymer beads (or imaginary time slices) used in
      the calculation. However, this estimate neglects the fact that the potential
      energies of many systems can be decomposed into a sum of rapidly varying short
      range and slowly varying long-range contributions. For such systems, the
      computational effort of the path integral simulation can be reduced considerably
      by evaluating the long-range forces on a contracted ring polymer with fewer beads
      than are needed to evaluate the short-range forces. This idea is developed and
      then illustrated with an application to a flexible model of liquid water in which
      the intramolecular forces are evaluated with 32 beads, the oxygen-oxygen Lennard
      Jones forces with seven, and the intermolecular electrostatic forces with just
      five. The resulting static and dynamic properties are within a few percent of
      those of a full 32-bead calculation, and yet they are obtained with a
      computational effort less than six times (rather than 32 times) that of a
      classical simulation. We hope that this development will encourage future studies
      of quantum mechanical fluctuations in liquid water and aqueous solutions and in
      many other systems with similar interaction potentials.

PMID- 18624515
TI  - Effective thermostat induced by coarse graining of simple point charge water.
AB  - We investigate how the transport properties of a united atom fluid with a
      dissipative particle dynamics thermostat depend on the functional form and
      magnitude of both the conservative and the stochastic interactions. We
      demonstrate how the thermostat strongly affects the hydrodynamics, especially
      diffusion, viscosity, and local escape times. As model system we use simple point
      charge (SPC) water, from which projected trajectories are used to determine the
      effective interactions in the united atom model. The simulation results support
      our argument that the thermostat should be viewed as an integral part of the
      coarse-grained dynamics rather than a tool for approaching thermal equilibrium.
      As our main result we show that the united atom model with the adjusted effective
      interactions approximately reproduces the diffusion constant and the viscosity of
      the underlying detailed SPC water model.

PMID- 18624516
TI  - A hierarchical transition state search algorithm.
AB  - A hierarchical transition state search algorithm is developed and its
      implementation in the density functional theory program deMon2k is described.
      This search algorithm combines the double ended saddle interpolation method with
      local uphill trust region optimization. A new formalism for the incorporation of
      the distance constrain in the saddle interpolation method is derived. The
      similarities between the constrained optimizations in the local trust region
      method and the saddle interpolation are highlighted. The saddle interpolation and
      local uphill trust region optimizations are validated on a test set of 28
      representative reactions. The hierarchical transition state search algorithm is
      applied to an intramolecular Diels-Alder reaction with several internal rotors,
      which makes automatic transition state search rather challenging. The obtained
      reaction mechanism is discussed in the context of the experimentally observed
      product distribution.

PMID- 18624517
TI  - Molecular applications of state-specific multireference perturbation theory to
      HF, H2O, H2S, C2, and N2 molecules.
AB  - In view of the initial success of the complete active space (CAS) based size
      extensive state-specific multireference perturbation theory (SS-MRPT) [J. Phys.
      Chem. A 103, 1822 (1999)] for relatively diverse yet simple chemically
      interesting systems, in this paper, we present the computation of the potential
      energy curves (PEC) of systems with arbitrary complexity and generality such as
      HF, H(2)O, H(2)S, C(2), and N(2) molecules. The ground states of such systems
      (and also low-lying singlet excited states of C(2)) possess multireference
      character making the description of the state difficult with single-reference
      (SR) methods. In this paper, we have considered the Moller-Plesset (MP)
      partitioning scheme [SS-MRPT(MP)] method. The accuracy of energies generated via
      SS-MRPT(MP) method is tested through comparison with other available results.
      Comparison with FCI has also been provided wherever available. The accuracy of
      this method is also demonstrated through the calculations of NPE (nonparallelism
      error) and the computation of the spectroscopic constants of all the above
      mentioned systems. The quality of the computed spectroscopic constants is
      established through comparison with the corresponding experimental and FCI
      results. Our numerical investigations demonstrate that the SS-MRPT(MP) approach
      provides a balanced treatment of dynamical and non-dynamical correlations across
      the entire PECs of the systems considered.

PMID- 18624518
TI  - Stable long-time semiclassical description of zero-point energy in high
      dimensional molecular systems.
AB  - Semiclassical implementation of the quantum trajectory formalism [J. Chem. Phys.
      120, 1181 (2004)] is further developed to give a stable long-time description of
      zero-point energy in anharmonic systems of high dimensionality. The method is
      based on a numerically cheap linearized quantum force approach; stabilizing terms
      compensating for the linearization errors are added into the time-evolution
      equations for the classical and nonclassical components of the momentum operator.
      The wave function normalization and energy are rigorously conserved. Numerical
      tests are performed for model systems of up to 40 degrees of freedom.

PMID- 18624519
TI  - On the local representation of the electronic momentum operator in atomic
      systems.
AB  - The local quantum theory is applied to the study of the momentum operator in
      atomic systems. Consequently, a quantum-based local momentum expression in terms
      of the single-electron density is determined. The limiting values of this
      function correctly obey two fundamental theorems: Kato's cusp condition and the
      Hoffmann-Ostenhof and Hoffmann-Ostenhof exponential decay. The local momentum
      also depicts the electron shell structure in atoms as given by its local maxima
      and inflection points. The integration of the electron density in a shell gives
      electron populations that are in agreement with the ones expected from the
      Periodic Table of the elements. The shell structure obtained is in agreement with
      the higher level of theory computations, which include the Kohn-Sham kinetic
      energy density. The average of the local kinetic energy associated with the local
      momentum is the Weizsacker kinetic energy. In conclusion, the local
      representation of the momentum operator provides relevant information about the
      electronic properties of the atom at any distance from the nucleus.

PMID- 18624520
TI  - Efficient quantum calculations of vibrational states of vinylidene in full
      dimensionality: a scheme with combination of methods.
AB  - Full-dimensional quantum calculations of vibrational states of C(2)H(2) and
      C(2)D(2) are performed in the high-energy region (above 20,400 cm(-1) relative to
      the acetylene minimum). The theoretical scheme is a combination of several
      methods. To exploit the full parity and permutation symmetry, the CC-HH diatom
      diatom Jacobi coordinates are chosen; phase space optimization in combination
      with physical considerations is used to obtain an efficient radial discrete
      variable representation, whereas a basis contraction scheme is applied for
      angular coordinates. The preconditioned inexact spectral transform method
      combined with an efficient preconditioner is employed to compute eigenstates
      within a desired spectral window. The computation is efficient. More definite
      assignments on vinylidene states than previous studies are acquired using the
      normal mode projection; in particular, a consistent analysis of the nu(1)
      (symmetric CH stretch) state is provided. The computed vinylidene vibrational
      energy levels are in general good agreement with experiment, and several
      vinylidene states are reported for the first time.

PMID- 18624521
TI  - Algorithmic decoherence time for decay-of-mixing non-Born-Oppenheimer dynamics.
AB  - The performance of an analytical expression for algorithmic decoherence time is
      investigated for non-Born-Oppenheimer molecular dynamics. There are two terms in
      the function that represents the dependence of the decoherence time on the system
      parameters; one represents decoherence due to the quantum time-energy uncertainty
      principle and the other represents a back reaction from the decoherent force on
      the classical trajectory. We particularly examine the question of whether the
      first term should dominate. Five one-dimensional two-state model systems that
      represent limits of multidimensional nonadiabatic dynamics are designed for
      testing mixed quantum-classical methods and for comparing semiclassical
      calculations with exact quantum calculations. Simulations are carried out with
      the semiclassical Ehrenfest method (SE), Tully's fewest switch version (TFS) of
      the trajectory surface hopping method, and the decay-of-mixing method with
      natural switching, coherent switching (CSDM), and coherent switching with
      reinitiation (CSDM-D). The CSDM method is demonstrated to be the most accurate
      method, and it has several desirable features: (i) It behaves like the
      representation-independent SE method in the strong nonadiabatic coupling regions;
      (ii) it behaves physically like the TFS method in noninteractive region; and
      (iii) the trajectories are continuous with continuous momenta. The CSDM method is
      also demonstrated to balance coherence well with decoherence, and the results are
      nearly independent of whether one uses the adiabatic or diabatic representation.
      The present results provide new insight into the formulation of a physically
      correct decoherence time to be used with the CSDM method for non-Born-Oppenheimer
      molecular dynamic simulations.

PMID- 18624522
TI  - Accurate ab initio density fitting for multiconfigurational self-consistent field
      methods.
AB  - Using Cholesky decomposition and density fitting to approximate the electron
      repulsion integrals, an implementation of the complete active space self
      consistent field (CASSCF) method suitable for large-scale applications is
      presented. Sample calculations on benzene, diaquo-tetra-mu-acetato-dicopper(II),
      and diuraniumendofullerene demonstrate that the Cholesky and density fitting
      approximations allow larger basis sets and larger systems to be treated at the
      CASSCF level of theory with controllable accuracy. While strict error control is
      an inherent property of the Cholesky approximation, errors arising from the
      density fitting approach are managed by using a recently proposed class of
      auxiliary basis sets constructed from Cholesky decomposition of the atomic
      electron repulsion integrals.

PMID- 18624523
TI  - Optimal protocols for minimal work processes in underdamped stochastic
      thermodynamics.
AB  - For systems in an externally controllable time-dependent potential, the optimal
      protocol minimizes the mean work spent in a finite-time transition between two
      given equilibrium states. For overdamped dynamics which ignores inertia effects,
      the optimal protocol has been found to involve jumps of the control parameter at
      the beginning and end of the process. Including the inertia term, we show that
      this feature not only persists but that even delta-peak-like changes of the
      control parameter at both boundaries make the process optimal. These results are
      obtained by analyzing two simple paradigmatic cases: First, a Brownian particle
      dragged by a harmonic optical trap through a viscous fluid and, second, a
      Brownian particle subject to an optical trap with time-dependent stiffness. These
      insights could be used to improve free energy calculations via either
      thermodynamic integration or "fast growth" methods using Jarzynski's equality.

PMID- 18624524
TI  - Optimizing the sampling and staging for simulations of rare events via forward
      flux sampling schemes.
AB  - In this work, we present an adaptive algorithm to optimize the phase space
      sampling for simulations of rare events in complex systems via forward flux
      sampling (FFS) schemes. In FFS, interfaces are used to partition the phase space
      along an order parameter lambda connecting the initial and final regions of
      interest. Since the kinetic "bottleneck" regions along the order parameter are
      not usually known beforehand, an adaptive procedure is used that first finds
      these regions by estimating the rate constants associated with reaching
      subsequent interfaces; thereafter, the FFS simulation is reset to concentrate the
      sampling on those bottlenecks. The approach can optimize for either the number
      and position of the interfaces (i.e., optimized lambda phase staging) or the
      number M of fired trial runs per interface (i.e., the {M(i)} set) to minimize the
      statistical error in the rate constant estimation per simulation period. For
      example, the optimization of the lambda staging leads to a net constant flux of
      partial trajectories between interfaces and hence a constant flux of connected
      paths throughout the region between the two end states. The method is
      demonstrated for several test systems, including the folding of a lattice
      protein. It is shown that the proposed approach leads to an optimized lambda
      staging and {M(i)} set which increase the computational efficiency of the
      sampling algorithm.

PMID- 18624525
TI  - Measurement of nonequilibrium entropy from space-time thermodynamic integration.
AB  - The entropy of a system transiently driven out of equilibrium by a time
      inhomogeneous stochastic dynamics is first expressed as a transient response
      function generalizing the nonlinear Kawasaki-Crooks response. This function is
      then reformulated into three statistical averages defined over ensembles of
      nonequilibrium trajectories. The first average corresponds to a space-time
      thermodynamic perturbation relation, while the two following ones correspond to
      space-time thermodynamic integration relations. Provided that trajectories are
      initiated starting from a distribution of states that is analytically known, the
      ensemble averages are computationally amenable to Markov chain Monte Carlo
      methods. The relevance of importance sampling in path ensembles is confirmed in
      practice by computing the nonequilibrium entropy of a driven toy system. We
      finally study a situation where the dynamics produces entropy. In this case, we
      observe that space-time thermodynamic integration still yields converged
      estimates, while space-time thermodynamic perturbation turns out to converge very
      slowly.

PMID- 18624526
TI  - Nonlinear optical property calculations of polyynes with long-range corrected
      hybrid exchange-correlation functionals.
AB  - Polarizabilities (alpha), second-hyperpolarizabilities (gamma), and the gamma
      scaling factors (c) of polyynes [H-(C[triple bond]C)(n)-H, n = 1-8] were
      evaluated using the long-range corrected (LC) density functional theory (DFT) and
      LC-DFT with a short-range Gaussian attenuation (LCgau), as well as high quality
      wavefunction methods. We show that the c values obtained from LC- and LCgau-DFT
      are consistent with those from CCSD(T) calculations. Furthermore, the polyyne c
      values we obtained are seen to be smaller than the c values derived from
      previously calculated polyene gamma values [Sekino et al., J. Chem. Phys. 126,
      014107 (2007)] in all the methods we consider. We compare our results with those
      obtained experimentally [Shepkov et al., J. Chem. Phys. 120, 6807 (2004).] from
      end-capped polyynes [i-Pr(3)Si-(C[triple bond]C)(n)-Sii-Pr(3)], which show larger
      c values for polyynes than polyenes. Our alpha and gamma calculations with i
      Pr(3)Si-(C[triple bond]C)(n)-Sii-Pr(3) (n = 4, 5, 6, and 8) show that i-Pr(3)Si-
      may participate in pi molecular orbital delocalization, which can unexpectedly
      affect the c value. We also confirm the importance of molecular geometry in these
      nonlinear optical calculations. We find that while LC- and LCgau-DFT excellently
      reproduce experimental geometries and bond length alternation (BLA), MP2
      optimized geometries have a BLA that is too short to be used for accurate alpha
      and gamma calculations.

PMID- 18624527
TI  - An analytic model of rotationally inelastic collisions of polar molecules in
      electric fields.
AB  - We present an analytic model of thermal state-to-state rotationally inelastic
      collisions of polar molecules in electric fields. The model is based on the
      Fraunhofer scattering of matter waves and requires Legendre moments
      characterizing the "shape" of the target in the body-fixed frame as its input.
      The electric field orients the target in the space-fixed frame and thereby
      effects a striking alteration of the dynamical observables: both the phase and
      amplitude of the oscillations in the partial differential cross sections undergo
      characteristic field-dependent changes that transgress into the partial integral
      cross sections. As the cross sections can be evaluated for a field applied
      parallel or perpendicular to the relative velocity, the model also offers
      predictions about steric asymmetry. We exemplify the field-dependent quantum
      collision dynamics with the behavior of the Ne-OCS((1)Sigma) and Ar-NO((2)Pi)
      systems. A comparison with the close-coupling calculations available for the
      latter system [Chem. Phys. Lett. 313, 491 (1999)] demonstrates the model's
      ability to qualitatively explain the field dependence of all the scattering
      features observed.

PMID- 18624528
TI  - Low-lying isomers of the B9(-) boron cluster: the planar molecular wheel versus
      three-dimensional structures.
AB  - The B(9)(-) cluster was found previously to be an unprecedented molecular wheel
      containing an octacoordinate planar boron with D(8h) symmetry in a combined
      photoelectron spectroscopy (PES) and theoretical study [H. J. Zhai et al., Angew.
      Chem., Int. Ed. 42, 6004 (2003)]. However, the PES spectra of B(9)(-) exhibit
      minor features that cannot be explained by the global minimum D(8h) structure,
      suggesting possible contributions from low-lying isomers at finite temperatures.
      Here we present Car-Parrinello molecular dynamics with simulated annealing
      simulations to fully explore the potential energy surface of B(9)(-) and search
      for low-lying isomers that may account for the minor PES features. We performed
      density functional theory (DFT) calculations with different exchange-correlation
      functionals and ab initio calculations at various levels of theory with different
      basis sets. Two three-dimensional low-lying isomers were found, both of C(s)
      symmetry, 6.29 (C(s)-2) and 10.23 (C(s)-1) kcal/mol higher in energy than the
      D(8h) structure at the highest CCSD(T) level of theory. Calculated detachment
      transitions from the C(s)-2 isomer are in excellent agreement with the minor
      features observed in the PES spectra of B(9)(-). The B(9)(-) cluster proves to be
      a challenge for most DFT methods and the calculated relative energies strongly
      depend on the exchange-correlation functionals, providing an excellent example
      for evaluating the accuracies of various DFT methods.

PMID- 18624529
TI  - Observation of the nd 1Delta(g) (n = 6, 7, and 8) Rydberg states of Na2 by
      optical-optical double resonance spectroscopy: L uncoupling and perturbations.
AB  - The nd (1)Delta(g) (n = 6, 7, and 8) Rydberg states of Na(2) correlating with the
      asymptotic limits of Na(3s) + Na(nd) have been observed using high-resolution cw
      optical-optical double resonance spectroscopy corresponding to the rovibrational
      transitions X (1)Sigma(g)(+)(v("),J(")) + h nu(pump) --> B (1)Pi(u)(v('),J(')) +
      h nu(probe) --> nd (1)Delta(g)(v,J). Totals of 104, 83, and 45 identified
      rovibrational e/f-parity levels in the ranges of v = 0-11, 11 < or = J < or = 83;
      v = 0-10, 11 < or = J < or = 83; and v = 0-10, 11 < or = J < or = 65, have been
      assigned to the 6d (1)Delta(g), 7d (1)Delta(g), and 8d (1)Delta(g) states,
      respectively. Using the observed quantum levels, molecular constants were
      determined from the Dunham fits of the e-parity levels and the Rydberg-Klein-Rees
      potential curves were constructed for the nd (1)Delta(g)(n = 6-8) states. The
      characteristics of the estimated Lambda-doubling splitting constants (q(0), q(v),
      and mu) with n(= 5-8) of the nd (1)Delta(g) series have been explored. Detailed
      investigations reveal that the nd (1)Delta(g)(n = 6-8) states involve L
      uncoupling from the internuclear axis and each of these states is affected by an
      asymmetric perturbation caused by the up and down adjacent states. The rotational
      branch intensity and position anomalies in the observed spectra of the nd
      (1)Delta(g) series (n = 5-8) of Na(2) lead to the conclusion that due to the
      effects of the L-uncoupling perturbations, the same l complexes approaching the
      same ion-core limits result in the same l-mixing processes which lead to the
      formation of the supercomplexes due to the anisotropy of the molecular-ion
      [Na(2)(+)(3s)] field. This would open up opportunities to study the effects of L
      uncoupling and perturbations in the nd series and high Rydberg states of other
      alkali dimers.

PMID- 18624530
TI  - Possible electronic decay channels in the ionization spectra of small clusters
      composed of Ar and Kr: a four-component relativistic treatment.
AB  - In this work single and double ionization spectra of the homo- and heteronuclear
      argon/krypton dimers and trimers are calculated by means of propagator methods
      where a four-component implementation was employed for the single ionizations.
      Scalar relativistic effects play only a minor role for the outer valence spectral
      structure, whereas spin-orbit coupling and electron correlation have to be
      treated adequately in order to reproduce the features correctly. Nonradiative
      decay mechanisms of subvalence vacancies in the argon and krypton dimers and
      trimers are discussed both for the interatomic Coulombic decay and the electron
      transfer mediated decay (ETMD). In the heteronuclear triatomic system which
      serves as a model for larger clusters, a possible ETMD process of the Ar 3s
      vacancy is found for the linear arrangement of the atoms. In the bent
      configuration the ETMD channel is closed.

PMID- 18624531
TI  - Cumulative reaction probabilities and transition state properties: a study of the
      F + H2 reaction and its deuterated isotopic variants.
AB  - A comparative quantum mechanical (QM) and quasiclassical trajectory (QCT) study
      of the cumulative reaction probabilities (CRPs) is presented in this work for the
      F + H(2) reaction and its isotopic variants for low values of the total angular
      momentum J. The agreement between the two sets of calculations is very good with
      the exception of some features whose origin is genuinely QM. The agreement also
      extends to the CRP resolved in the helicity quantum number k. The most remarkable
      feature is the steplike structure, which becomes clearly distinct when the CRPs
      are resolved in odd and even rotational states j. The analysis of these steps
      shows that each successive increment is due to the opening of the consecutive
      rovibrational states of the H(2) or D(2) molecule, which, in this case, nearly
      coincide with those of the transition state. Moreover, the height of each step
      reflects the number of helicity states compatible with a given J and j values,
      thus indicating that the various helicity states for a specific j have basically
      the same contribution to the CRPs at a given total energy. As a consequence, the
      dependence with k of the reactivity is practically negligible, suggesting very
      small steric restrictions for any possible orientation of the reactants. This
      behavior is in marked contrast to that found in the D + H(2) reaction, wherein a
      strong k dependence was found in the threshold and magnitude of the CRP. The
      advantages of a combined QCT and QM approaches to the study of CRPs are
      emphasized in this work.

PMID- 18624532
TI  - Phase behavior of a simple lattice model with a two-scale repulsive interaction.
AB  - The properties of a simple one-dimensional lattice model with two repulsive
      ranges are studied in terms of its analytic solution. Its phase behavior is
      characterized by the presence of a disorder-order-disorder transition (or a fluid
      solid-fluid transition in lattice gas language). A similar situation was
      discussed by Hemmer and Stell [Phys. Rev. Lett. 24, 1284 (1970)] when considering
      the purely repulsive version of their ramp potential. The melting of the solid
      phase, when pressure is increased along an isotherm, is a feature common to both
      models and one of the characteristic features of water.

PMID- 18624533
TI  - On the mechanism of photoinduced phase transitions in ternary liquid crystal
      systems near thermal equilibrium.
AB  - According to their phase diagram, polyalkyl glycol ether dissolved in ternary
      solutions (water, alcane, and cyclohexane) lead to the formation of either liquid
      crystal phases or microemulsion phases. By photosensitization of the ternary
      system with laser dyes and choosing the adequate concentration and temperature
      conditions of these lyotropic systems, it is possible to photoinduce the phase
      transitions from the microemulsion phase to the liquid crystal phase (and vice
      versa). The phototransformation conditions were chosen in such a way that the
      system is in thermal equilibrium during the entire phase transition. The method
      of photo small angle x-ray scattering has been applied to investigate the
      mechanism of photoinduced phase transition. Spectroscopically, the mechanism of
      photoinduced phase transition has been characterized by optical absorption and
      emission techniques.

PMID- 18624534
TI  - Hard-sphere perturbation theory for a model of liquid Ga.
AB  - Investigating thermodynamic properties of a model for liquid Ga, we have extended
      the application of the hard-sphere (HS) perturbation theory to an interatomic
      pair potential that possesses a soft repulsive core and a long-range oscillatory
      part. The model is interesting for displaying a discontinuous jump on the main
      peak position of the radial distribution function at some critical density. At
      densities less than this critical value, the effective HS diameter of the model,
      estimated by the variational HS perturbation theory, has a substantial reduction
      with increasing density. Thus, the density dependence of the packing fraction of
      the HS reference fluid has an anomalous behavior, with a negative slope, within a
      density region below the critical density. By adding a correction term originally
      proposed by Mon to remedy the inherent deficiency of the HS perturbation theory,
      the extended Mansoori-Canfield/Rasaiah-Stell theory [J. Chem. Phys. 120, 4844
      (2004)] very accurately predicts the Helmholtz free energy and entropy of the
      model, including an excess entropy anomaly. Almost occurring in the same density
      region, the excess entropy anomaly is found to be associated with the anomalous
      packing faction of the HS fluid.

PMID- 18624535
TI  - Tunneling dynamics with a mixed quantum-classical method: quantum corrected
      propagator combined with frozen Gaussian wave packets.
AB  - The recently developed mixed quantum-classical propagation method is extended to
      treat tunneling effects in multidimensional systems. Formulated for systems
      consisting of a quantum primary part and a classical bath of heavier particles,
      the method employs a frozen Gaussian description for the bath degrees of freedom,
      while the dynamics of the quantum subsystem is governed by a corrected
      propagator. The corrections are defined in terms of matrix elements of zeroth
      order propagators. The method is applied to a model system of a double-well
      potential bilinearly coupled to a harmonic oscillator. The extension of the
      method, which includes nondiagonal elements of the correction propagator, enables
      an accurate treatment of tunneling in an antisymmetric double-well potential.

PMID- 18624536
TI  - Intensity enhancement and selective detection of proximate solvent molecules by
      molecular near-field effect in resonance hyper-Raman scattering.
AB  - A new molecular phenomenon associated with resonance hyper-Raman (HR) scattering
      in solution has been discovered. Resonance HR spectra of all-trans-beta-carotene
      and all-trans-lycopene in various solvents exhibited several extra bands that
      were not assignable to the solute but were unequivocally assigned to the
      solvents. Neat solvents did not show detectable HR signals under the same
      experimental conditions. Similar experiments with all-trans-retinal did not
      exhibit such enhancement either. All-trans-beta-carotene and all-trans-lycopene
      have thus been shown to induce enhanced HR scattering of solvent molecules
      through a novel molecular effect that is not associated with all-trans-retinal.
      We call this new effect the "molecular near-field effect." In order to explain
      this newly found effect, an extended vibronic theory of resonance HR scattering
      is developed where the vibronic interaction including the proximate solvent
      molecule (intermolecular vibronic coupling) is explicitly introduced in the
      solute hyperpolarizability tensor. The potential of "molecular near-field HR
      spectroscopy," which selectively detects molecules existing in the close vicinity
      of a HR probe in complex chemical or biological systems, is discussed.

PMID- 18624537
TI  - Cluster-variation approximation for a network-forming lattice-fluid model.
AB  - We consider a three-dimensional lattice model of a network-forming fluid, which
      has been recently investigated by Girardi et al. by means of Monte Carlo
      simulations [J. Chem. Phys. 126, 064503 (2007)], with the aim of describing water
      anomalies. We develop an approximate semianalytical calculation, based on a
      cluster-variation technique, which turns out to reproduce almost quantitatively
      different thermodynamic properties and phase transitions determined by the Monte
      Carlo method. Nevertheless, our calculation points out the existence of two
      different phases characterized by long-range orientational order, and of critical
      transitions between them and to a high-temperature orientationally disordered
      phase. Also, the existence of such critical lines allows us to explain certain
      "kinks" in the isotherms and isobars determined by the Monte Carlo analysis. The
      picture of the phase diagram becomes much more complex and richer, though
      unfortunately less suitable to describe real water.

PMID- 18624538
TI  - Transport properties of Mie(14,7) fluids: molecular dynamics simulation and
      theory.
AB  - An extensive computer simulation study is presented for the self-diffusion
      coefficient, the shear viscosity, and the thermal conductivity of Mie(14,7)
      fluids. The time-correlation function formalism of Green-Kubo is utilized in
      conjunction with molecular dynamics (MD) simulations. In addition to molecular
      simulations, the results of a recent study [A. Eskandari Nasrabad, J. Chem. Phys.
      128, 154514 (2008)] for the mean free volume are applied to calculate the self
      diffusion coefficients within a free volume theory framework. A detailed
      comparison between the MD simulation and free volume theory results for the
      diffusion coefficient is given. The density fluctuation theory of shear viscosity
      is used to compute the shear viscosity and the results are compared to those from
      MD simulations. The density and temperature dependences of different time
      correlation functions and transport coefficients are studied and discussed.

PMID- 18624539
TI  - The importance of polarizability in the modeling of solubility: quantifying the
      effect of solute polarizability on the solubility of small nonpolar solutes in
      popular models of water.
AB  - In recent work by Paschek [J. Chem. Phys. 120, 6674 (2004)] and others [see H.
      Docherty et al., J. Chem. Phys. 125, 074510 (2006) for a review] it has been
      suggested that, when coupled to a simple Lennard-Jones model for various small
      nonpolar solute molecules, the most common models of water (e.g., SPC/E and
      TIP4P) fail to reproduce quantitatively the solubility of small nonpolar solute
      molecules in water due in part to failing to account for polarization of the
      solute molecule. Given the importance of such systems as test-case prototype
      models of the solubility of proteins and biomolecules, in this work, we
      investigate the impact of using a polarizable solute model with the SPC/E, TIP3P,
      TIP4P, TIP4P-Ew, and TIP4P/2005 rigid water models. Specifically we consider Ne,
      Ar, Kr, Xe, and methane as solutes. In all cases we observe that the use of a
      polarizable solute improves agreement between experiment and simulations, with
      the best agreement seen for the largest solutes, Kr, CH(4), and Xe and the modern
      reparametrizations of the TIP4P model, i.e., the TIP4P-Ew and TIP4P/2005 models.

PMID- 18624540
TI  - Quantum dynamic of sticking of a H atom on a graphite surface.
AB  - A quantum study of the sticking of a hydrogen atom chemisorbed onto graphite
      (0001) surface was carried out also including the phonon modes of the system in
      the collinear scattering approximation. A new model was developed to extract the
      substrate vibrational modes from density functional theory (DFT) calculation and
      include them in the total system dynamics. The resulting coupled-channel
      equations are numerically developed along time using the wave packet methods. The
      sticking coefficients are calculated for hydrogen atoms incident energies ranging
      from 0.17 and 1.3 eV for a surface temperature of 10 K and between 0.17 and 0.2
      eV for a surface temperature of 150 K. The results are found to be in good
      agreement with the experimental work.

PMID- 18624541
TI  - An interpretative model for the anomalous behavior of some excess properties in
      mixed liquid systems: a relationship between excess molar volumes and excess
      compressibilities in strongly self-aggregated fluids.
AB  - A simple theoretical model based on the hole theory of the liquid state has been
      developed in order to find a relationship between the excess molar volume and the
      excess compressibility of a two-component fluid. The model has been extended to
      investigate strongly associating fluids dissolved in an apolar solvent. Such a
      model nicely explains our recent results obtained from a Brillouin scattering
      study of the nonideal mixture between tert-butyl alcohol and 2-2(') dimethyl
      butane. Its validity, however, seems to be rather general and it could be
      usefully applied to rationalize the excess properties of several nonideal binary
      fluid mixtures.

PMID- 18624542
TI  - Microscopic solvation of a lithium atom in water-ammonia mixed clusters: solvent
      coordination and electron localization in presence of a counterion.
AB  - The microsolvation structures and energetics of water-ammonia mixed clusters
      containing a lithium atom, i.e., Li(H(2)O)(n)(NH(3)), n = 1-5, are investigated
      by means of ab initio theoretical calculations. Several structural aspects such
      as the solvent coordination to the metal ion and binding motifs of the free
      valence electron of the metal are investigated. We also study the energetics
      aspects such as the dependence of vertical ionization energies on the cluster
      size, and all these structural and energetics aspects are compared to the
      corresponding results of previously studied anionic water-ammonia clusters
      without a metal ion. It is found that the Li-O and Li-N interactions play a very
      important role in stabilizing the lithium-water-ammonia clusters, and the
      presence of these metal ion-solvent interactions also affect the characteristics
      of electron solvation in these clusters. This is seen from the spatial
      distribution of the singly occupied molecular orbital (SOMO) which holds the
      ejected valence electron of the Li atom. For very small clusters, SOMO electron
      density is found to exist mainly at the vicinity of the Li atom, whereas for
      larger clusters, it is distributed outside the first solvation shell. The free
      dangling hydrogens of water and ammonia molecules are involved in capturing the
      SOMO electron density. In some of the conformers, OH{e}HO and OH{e}HN types of
      interactions are found to be present. The presence of the metal ion at the center
      of the cluster ensures that the ejected electron is solvated at a surface state
      only, whereas both surface and interiorlike states were found for the free
      electron in the corresponding anionic clusters without a metal ion. The vertical
      ionization energies of the present clusters are found to be higher than the
      vertical detachment energies of the corresponding anionic clusters which signify
      a relatively stronger binding of the free electron in the presence of the
      positive metal counterion. The shifts in different vibrational frequencies are
      also calculated for the larger clusters, and the results are discussed for some
      of the selective modes of water and ammonia molecules that are directly
      influenced by the location and hydrogen bonding state of these molecules in the
      clusters.

PMID- 18624543
TI  - Nucleation theory in Langevin's approach and lifetime of a Brownian particle in
      potential wells.
AB  - The multivariable theory of nucleation suggested by Alekseechkin [J. Chem. Phys.
      124, 124512 (2006)] is further developed in the context of Langevin's approach.
      The use of this approach essentially enhances the capability of the nucleation
      theory, because it makes possible to consider the cases of small friction which
      are not taken into account by the classical Zel'dovich-Frenkel theory and its
      multivariable extensions. The procedure for the phenomenological determination of
      the nucleation parameters is described. Using the similarity of the Kramers model
      with that of nucleation, the lifetime of a Brownian particle in potential wells
      in various dimensionalities is calculated with the help of the expression for the
      steady state nucleation rate.

PMID- 18624544
TI  - Fourier transform infrared spectroscopy of azide and cyanate ion pairs in AOT
      reverse micelles.
AB  - Evidence for ion pair formation in aqueous bis(2-ethylhexyl) sulfosuccinate (AOT)
      reverse micelles (RMs) was obtained from infrared spectra of azide and cyanate
      with Li(+), Na(+), K(+), and NH(4)(+) counterions. The anions' antisymmetric
      stretching bands near 2000 cm(-1) are shifted to higher frequency (blueshifted)
      in LiAOT and to a lesser extent in NaAOT, but they are very similar to those in
      bulk water with K(+) and NH(4)(+) as the counterions. The shifts are largest for
      low values of w(o) = [water]/[AOT] and approach the bulk value with increasing
      w(o). The blueshifts are attributed to ion pairing between the anions and the
      counterions. This interpretation is reinforced by the similar trend
      (Li(+)>Na(+)>K(+)) for producing contact ion pairs with the metal cations in bulk
      dimethyl sulfoxide (DMSO) solutions. We find no evidence of ion pairs being
      formed in NH(4)AOT RMs, whereas ammonium does form ion pairs with azide and
      cyanate in bulk DMSO. Studies are also reported for the anions in formamide
      containing AOT RMs, in which blueshifts and ion pair formation are observed more
      than in the aqueous RMs. Ion pairs are preferentially formed in confined RM
      systems, consistent with the well established ideas that RMs exhibit reduced
      polarity and a disrupted hydrogen bonding network compared to bulk water and that
      ion-specific effects are involved in mediating the structure of species at
      interfaces.

PMID- 18624545
TI  - Structural and dynamical properties of a core-softened fluid in a supercritical
      region.
AB  - We present a theoretical study of the structural, thermodynamic, and transport
      properties of a supercritical fluid comprising particles interacting via
      isotropic attractive core-softened potential. The shear viscosity and self
      diffusion coefficient are computed on the basis of the mode-coupling theory, with
      required structural input obtained from the thermodynamically self-consistent
      integral equation theory. We also consider dilute solutes in a core-softened
      fluid and use the anisotropic integral equation theory to obtain the solute
      solute potential of mean force, which yields the second virial coefficient. We
      analyze its dependence on the solvent density and solute-solvent interaction
      strength.

PMID- 18624546
TI  - Diffusion trapping times and dynamic percolation in an Ising system.
AB  - We address the problem of diffusion through dynamic Ising network structures
      using random walkers (RWs) whose net displacements are partitioned into two
      contributions, arising from (1) transport through neighboring "conducting"
      clusters and (2) self-diffusion of the site on which the RW finds itself,
      respectively. At finite temperatures, the conducting clusters in the network
      exhibit correlated dynamic behavior, making our model system different to most
      prior published work, which has largely been at the random percolation limit. We
      also present a novel heuristic scaling analysis for this system that utilizes a
      new scaling exponent theta(z) for representing RW trapping time as a function of
      "distance" from the dynamic percolation transition. Simulation results in two
      dimensional networks show that when theta(z) = 2, a value found from independent
      physical arguments, our scaling equations appear to capture universal behavior in
      the system, at both the random percolation (infinite temperature) and finite
      temperature conditions studied. This study suggests that the model and the
      scaling approach given here should prove useful for studying transport in
      physical systems showing dynamic disorder.

PMID- 18624547
TI  - Ab initio study of charge transport of hydrogen functionalized palladium wires.
AB  - We present ab initio calculations of transport properties of palladium wires in
      the presence of hydrogen. Detailed investigations have been conducted with a pure
      palladium wire and with opening a gap inside the wire in which the transition
      between point contact regime and tunneling regime occurs. The effect of the
      presence of hydrogen in the gap is studied for different ranges of the gap size.
      The hydrogen mediated transport in the contact and tunneling regimes of the gap
      are analyzed and compared. It is predicted that only in large enough distances
      the hydrogen presence increases the conductance. The effect of additional
      hydrogen molecules on the gap is also studied.

PMID- 18624548
TI  - Dark channels in resonant tunneling transport through artificial atoms.
AB  - We investigate sequential tunneling through a multilevel quantum dot confining
      multiple electrons in the regime where several channels are available for
      transport within the bias window. By analyzing solutions to the master equations
      of the reduced density matrix, we give general conditions on when the presence of
      a second transport channel in the bias window quenches transport through the
      quantum dot. These conditions are in terms of distinct tunneling anisotropies
      which may aid in explaining the occurrence of negative differential conductance
      in quantum dots in the nonlinear regime.

PMID- 18624549
TI  - Using circularly polarized luminescence to probe exciton coherence in disordered
      helical aggregates.
AB  - Circularly polarized emission from helical MOPV4 aggregates is studied
      theoretically based on a Hamiltonian including excitonic coupling, exciton phonon
      coupling, and site disorder. The latter is modeled via a Gaussian distribution of
      site energies. The frequency dependence of the circularly polarized luminescence
      dissymmetry g(lum)(omega) contains structural information about the low-energy
      neutral (excitonic) polaron from which emission originates. Near the 0-0 emission
      frequency, g(lum)(omega) provides a measure of the exciton coherence length,
      while at lower energies, in the vicinity of the sideband frequencies,
      g(lum)(omega) probes the polaron radius. The present work focuses on how the 0-0
      dissymmetry, g(lum)(0-0), relates to the emitting exciton's coherence function,
      from which the coherence length is deduced. In the strong disorder limit where
      the exciton is localized on a single chromophore, g(lum)(0-0) is zero. As
      disorder is reduced and the coherence function expands, /g(lum)(0-0)/ increases
      more rapidly than the sideband dissymmetries, resulting in a pronounced surge in
      g(lum)(omega) near the 0-0 transition frequency. The resulting spectral shape of
      g(lum)(omega) is in excellent agreement with recent experiments on MOPV4
      aggregates. In the limit of very weak disorder, corresponding to the motional
      narrowing regime, the coherence function extends over the entire helix. In this
      region, g(lum)(0-0) undergoes a surprising sign reversal but only for helices
      which are between n+12 and n+1 complete turns (n = 0,1,...). This unusual sign
      change is due to the dependence of the rotational line strength on long-range
      exciton coherences which are also responsible for a heightened sensitivity of
      g(lum)(omega) to long-range excitonic coupling.

PMID- 18624550
TI  - Pseudocritical or hysteresis temperature versus pore size for simple fluids
      confined in cylindrical nanopores.
AB  - The adsorption/desorption isotherms measured in nanoporous materials generally
      present a hysteresis. The hysteresis shrinks upon increasing the temperature (for
      a given pore size) or decreasing the pore size (for a given temperature), until
      it finally disappears at the so-called hysteresis (or pseudocritical) temperature
      T(h) or hysteresis (or pseudocritical) pore size R(h), not to be confused with a
      true critical point. In this paper, a Monte Carlo approach allowed calculating
      the surface free energy of confined fluid along the adsorption/desorption
      isotherms for various cylindrical pore sizes and temperatures. A simple
      phenomenological model then allowed exploiting these results to determine the
      relation between T(h) and R(h). The prediction is compared to various literature
      models and experimental data, showing agreement within uncertainties. On the
      other hand, the simulations cannot be used directly to predict T(h) and R(h)
      since they significantly overestimate the hysteresis width. The model predicts a
      nonlinear relation between the reduced hysteresis temperature and the inverse
      pore radius.

PMID- 18624551
TI  - The Wolf method applied to the liquid-vapor interface of water.
AB  - The Wolf method for the calculation of electrostatic interactions is applied in a
      liquid phase and at the liquid-vapor interface of water and its results are
      compared with those from the Ewald sums method. Molecular dynamics simulations
      are performed to calculate the radial distribution functions at room temperature.
      The interface simulations are used to obtain the coexisting densities and surface
      tension along the coexistence curve. The water model is a flexible version of the
      extended simple point charge model. The Wolf method gives good structural
      results, fair coexistence densities, and poor surface tensions as compared with
      those obtained using the Ewald sums method.

PMID- 18624552
TI  - An efficient and accurate decomposition of the Fermi operator.
AB  - We present a method to compute the Fermi function of the Hamiltonian for a system
      of independent fermions based on an exact decomposition of the grand-canonical
      potential. This scheme does not rely on the localization of the orbitals and is
      insensitive to ill-conditioned Hamiltonians. It lends itself naturally to linear
      scaling as soon as the sparsity of the system's density matrix is exploited. By
      using a combination of polynomial expansion and Newton-like iterative techniques,
      an arbitrarily large number of terms can be employed in the expansion, overcoming
      some of the difficulties encountered in previous papers. Moreover, this hybrid
      approach allows us to obtain a very favorable scaling of the computational cost
      with increasing inverse temperature, which makes the method competitive with
      other Fermi operator expansion techniques. After performing an in-depth
      theoretical analysis of computational cost and accuracy, we test our approach on
      the density functional theory Hamiltonian for the metallic phase of the LiAl
      alloy.

PMID- 18624553
TI  - Theoretical study of the nucleation/growth process of carbon clusters under
      pressure.
AB  - We used molecular dynamics and the empirical potential for carbon LCBOPII to
      simulate the nucleation/growth process of carbon clusters both in vacuum and
      under pressure. In vacuum, our results show that the growth process is
      homogeneous and yields mainly sp(2) structures such as fullerenes. We used an
      argon gas and Lennard-Jones potentials to mimic the high pressures and
      temperatures reached during the detonation of carbon-rich explosives. We found
      that these extreme thermodynamic conditions do not affect substantially the
      topologies of the clusters formed in the process. However, our estimation of the
      growth rates under pressure are in much better agreement with the values
      estimated experimentally than our vacuum simulations. The formation of sp(3)
      carbon was negligible both in vacuum and under pressure which suggests that
      larger simulation times and cluster sizes are needed to allow the nucleation of
      nanodiamonds.

PMID- 18624554
TI  - The work function of submonolayer cesium-covered gold: a photoelectron
      spectroscopy study.
AB  - Using visible and x-ray photoelectron spectroscopy, we measured the work function
      of a Au(111) surface at a well-defined submonolayer coverage of Cs. For a Cs
      coverage producing a photoemission maximum with a He-Ne laser, the work function
      is 1.61+/-0.08 eV, consistent with previous assumptions used to analyze
      vibrationally promoted electron emission. A discussion of possible Cs layer
      structures is also presented.

PMID- 18624555
TI  - Electronic structures of organic molecule encapsulated BN nanotubes under
      transverse electric field.
AB  - The electronic structures of boron nitride nanotubes (BNNTs) doped by different
      organic molecules under a transverse electric field were investigated via first
      principles calculations. The external field reduces the energy gap of BNNT, thus
      makes the molecular bands closer to the BNNT band edges and enhances the charge
      transfers between BNNT and molecules. The effects of the electric field direction
      on the band structure are negligible. The electric field shielding effect of BNNT
      to the inside organic molecules is discussed. Organic molecule doping strongly
      modifies the optical property of BNNT, and the absorption edge is redshifted
      under static transverse electric field.

PMID- 18624556
TI  - Local structure of liquid Ti: Ab initio molecular dynamics study.
AB  - Local order of liquid Ti is studied by ab initio molecular dynamics to address
      the unique liquid structure factor in experiments reported recently. The present
      study reveals that the local order of liquid Ti is in the form of fragments of
      the distorted icosahedral short range order, where the distortion is induced by
      strong bond order effects. We show that the fragments in the short-bond rich
      region separated from the background liquid account for the pronounced feature in
      structure factor of liquid Ti.

PMID- 18624557
TI  - Current through single conjugated molecules: calculations versus measurements.
AB  - We use density functional theory based nonequilibrium Green's function to
      calculate the current through the different rodlike molecules at the finite
      temperatures self-consistently, which was compared to the experimental
      measurements presented by Reichert et al. [Phys. Rev. Lett. 88, 176804 (2002)]
      and by Mayor et al. [Angew. Chem. Int. Ed. 42, 5834 (2003)], respectively. Our
      results agree with the measurements very well, especially for the bias around +/
      1.0 V. The investigation of the topological effect for the symmetrical molecule
      reveals the fact that the para position compound provides a considerably larger
      conductance than the meta one.

PMID- 18624558
TI  - A practical method to avoid bond crossing in two-dimensional dissipative particle
      dynamics simulations.
AB  - Dissipative particle dynamics (DPD) simulation technique is an effective method
      targeted on mesoscopic simulations in which the interactions between particles
      are soft. As a result, it inevitably causes bond crossing and interpenetration
      between particles. Here we develop a practical method based on the two
      dimensional DPD model which can extremely reduce the possibility of bond
      crossing. A rigid core is added to each particle by modifying the form of the
      conservative force in DPD so that the particles cannot penetrate each other. Then
      by adjusting the spring constant of the bond, we can impose a simple geometry
      constraint so that the bond crossing can hardly take place. Furthermore, we take
      into account an analytic geometry constraint in the polymerization model of DPD
      by which we can successfully avoid the severe bond crossing problem during bond
      generation in two dimensions. A parabola fitting between the pressure and the
      particle number density shows that our modified DPD model with small rigid cores
      can still be mapped onto the Flory-Huggins model, and the mesoscopic length scale
      of our simulations does not change. By analyzing the mean-square displacement of
      the innermost monomer and the center of mass of the chains, we find a t(8/15)
      power law of the polymer dynamics in our model instead of the Rouse prediction
      supporting the recent results in literature.

PMID- 18624559
TI  - The competition of double-, four-, and three-ring tubular B(3n) (n = 8-32)
      nanoclusters.
AB  - The geometry and electronic properties of three-ring tubular B(3n) clusters (n =
      8-32) are studied systematically with the density functional theory. It is
      composed of three staggered rings with the diameter of the middle ring larger
      than those of the two outer rings. With the increase in boron atom numbers, the
      three-ring tubular clusters are energetically more stable than the double-ring
      and four-ring tubular clusters and the buckled sheet clusters with hexagon holes.
      The average binding energy tends to the finite value. The stability is further
      analyzed through the natural bond orbital population analysis. The highest
      occupied and lowest unoccupied energy gaps become small, which demonstrates a
      favorable metallic property.

PMID- 18624560
TI  - Strong localization of positive charge in DNA induced by its interaction with
      environment.
AB  - We investigate a quantum state of positive charge in DNA. A quantum state of
      electron hole is determined by the competition of the pi-stacking interaction b
      sharing a charge between different base pairs and the interaction lambda with the
      local environment which attempts to trap charge. To determine which interaction
      dominates, we investigate charge quantum states in various (GC)(n) sequences
      choosing DNA parameters that satisfy experimental data for the balance of charge
      transfer rates G(+) <--> G(n)(+), n = 2, 3. We show that experimental data can be
      consistent with theory only assuming b<<lambda, meaning that charge is typically
      localized within the single G site. Consequently, as follows from our modeling
      consideration, any DNA duplex including the one consisting of identical base
      pairs cannot be considered as a molecular conductor. Our theory can be verified
      experimentally, measuring balance of charge transfer reactions G(+) <--> G(n)(+),
      n > or = 4 and comparing the experimental results with our predictions.

PMID- 18624562
TI  - New Lennard-Jones metastable phase.

PMID- 18624561
TI  - An efficient and accurate molecular alignment and docking technique using ab
      initio quality scoring.
AB  - An accurate and efficient molecular alignment technique is presented based on
      first principle electronic structure calculations. This new scheme maximizes
      quantum similarity matrices in the relative orientation of the molecules and uses
      Fourier transform techniques for two purposes. First, building up the numerical
      representation of true ab initio electronic densities and their Coulomb
      potentials is accelerated by the previously described Fourier transform Coulomb
      method. Second, the Fourier convolution technique is applied for accelerating
      optimizations in the translational coordinates. In order to avoid any
      interpolation error, the necessary analytical formulas are derived for the
      transformation of the ab initio wavefunctions in rotational coordinates. The
      results of our first implementation for a small test set are analyzed in detail
      and compared with published results of the literature. A new way of refinement of
      existing shape based alignments is also proposed by using Fourier convolutions of
      ab initio or other approximate electron densities. This new alignment technique
      is generally applicable for overlap, Coulomb, kinetic energy, etc., quantum
      similarity measures and can be extended to a genuine docking solution with ab
      initio scoring.

PMID- 18624563
TI  - Comment on "Resonant dissociative electron transfer of the presolvated electron
      to CCl4 in liquid: direct observation and lifetime of the CCl4(*-) transition
      state" [J. Chem. Phys. 128, 041102 (2008)].

PMID- 18624565
TI  - Comment on "Efficient Monte Carlo trial moves for polypeptide simulations" [J.
      Chem. Phys. 123, 174905 (2005)].

PMID- 18624566
TI  - Circadian phenotypes of Drosophila fragile x mutants in alternative genetic
      backgrounds.
AB  - Drosophila FMR1 mutants are models of human fragile X syndrome. They show a loss
      of locomotor activity rhythm and severe degradation of eclosion timing. We
      analyzed the circadian behavior of FMR1 mutants (dfmr1B55) in two genetic
      backgrounds, yellow white (yw) and Canton S (CS). The arrhythmic phenotype of
      circadian locomotor activity in constant darkness (DD) did not significantly
      change in either genetic background. Surprisingly, eclosion timing was completely
      restored by backcrossing dfmr1B55 with yw or CS flies. Morphological analysis of
      the small ventrally located lateral neurons of FMR1 mutants revealed that the
      dorsal-projection area was significantly larger in arrhythmic than rhythmic
      flies. In addition, dfmr1B55 mutants in both genetic backgrounds had a
      significantly lower evening peak in the light-dark (LD) cycle. These results
      indicate that lack of FMR1 does not affect eclosion timing, but alters locomotor
      activity patterns in both LD and DD conditions by affecting the arborization of
      small ventrally located lateral neurons. Thus, the FMR1 gene may regulate the
      circadian-related locomotor activity of Drosophila.

PMID- 18624567
TI  - Role of the tidal cycle in the gonadal development and spawning of the tropical
      wrasse Halichoeres trimaculatus.
AB  - Many wrasses on coral reefs exhibit daily spawning that peaks around daytime high
      tides. In this study, we examined tidal-related ovarian development in the
      threespot wrasse, Halichoeres trimaculatus, a species common on coral reefs in
      the Indo-Pacific Ocean. When the fish were collected in the morning at different
      tidal phases, the gonadosomatic index (GSI) and ovarian histology changed;
      concomitant with increases in GSI towards high tide, a clutch of the most
      advanced oocytes developed from vitellogenic to maturation stages. Ovulated eggs
      and post-ovulated follicles (POF) existed in most ovaries around high tide, but
      only POF remained around ebb tide, suggesting that spawning occurred during or
      after high tide. We noticed that tidal-related spawning was considerable in the
      morning and that most ovaries collected on the afternoon high tide exhibited post
      spawning features. This suggests that certain labrid species possess plasticity
      with regard to their spawning time and utilize potent environmental cues to
      ensure their reproductive success. When pieces of ovary were incubated with
      precursor steroids, high conversion of testosterone to 17beta-estradiol occurred
      during high and ebb tides, while that of 17alpha-hydroxyprogesterone to
      17alpha,20beta-dihydroxy-4-pregnen-3-one and 17alpha,20beta,21-trihydroxy-4
      pregnen-3-one was observed during low and flood tides. Incubation of pieces of
      ovary with human chorionic gonadotropin resulted in similar fluctuations in the
      steroid hormones with tidal phase. Production of these steroid hormones
      correlated with oocyte development in the ovaries and was probably regulated by
      gonadotropin. These results demonstrate that the daily cycle is fundamental for
      oocyte development, and that the tidal cycle is superimposed on this process.

PMID- 18624568
TI  - Changes in lipid droplet localization during embryogenesis of the silkworm,
      Bombyx mori.
AB  - Lipid droplets are considered one of the most important energy sources in
      lepidopteran eggs during late embryogenesis, but the process of their
      incorporation into the embryo is as yet unknown. The present study focused on the
      process of transition of lipid droplets from the extraembryonic yolk to the
      embryo of the silkworm Bombyx mori, using morphological and biochemical
      approaches. The morphological study revealed that the incorporation of lipid
      droplets from the extraembryonic yolk into the embryo occurs at three points and
      in three different ways during the development of the embryo. Some lipid droplets
      were translocated directly from the extraembryonic yolk to the embryo before the
      blastokinesis stage. However, the majority of lipid droplets together with the
      other components of the extraembryonic yolk were incorporated in the embryo via
      both morphogenetic inclusion during dorsal closure and ingestion of the
      extraembyonic yolk by the developing caterpillar prior to hatching. Similar
      results were obtained from the biochemical study. Thus, we propose that there are
      three steps in the incorporation of lipid droplets from the extraembryonic yolk
      into the embryo. In addition, morphological and biochemical data concerning the
      total amount of lipid droplets in the egg suggested that lipid droplets were
      mainly consumed during late embryogenesis, seeming to synchronize with tracheal
      development.

PMID- 18624569
TI  - Multiple sex pheromone genes are expressed in the abdominal glands of the smooth
      newt (Lissotriton vulgaris) and Montandon's Newt (L. montandoni) (Salamandridae).
AB  - The smooth newt (Lissotriton "Triturus" vulgaris) and Montandon's newt (L."T."
      montandoni) are sister species exhibiting pronounced differences in male
      secondary sexual traits but nevertheless hybridizing and producing fertile
      hybrids in nature. Since pheromonal communication is an important aspect of the
      reproductive biology of urodeles, structural differentiation of peptide
      pheromones and their receptors may contribute to incipient reproductive
      isolation. The aim of the study was the identification of genes encoding putative
      courtship pheromone precursors in two newt species and the reconstruction of
      phylogenetic relationships among them. Our analyses were based on cDNA obtained
      from the transcripts from the abdominal glands of male newts. We identified five
      unique cDNA sequences encoding the putative pheromone precursors in L. vulgaris
      and three additional unique sequences in L. montandoni. The results indicate that
      in the abdominal glands of Lissotriton newts more than one pheromone-encoding
      gene is expressed and that these loci form a gene family. Phylogenetic analysis
      indicates that the divergence of at least some of these genes predates the
      radiation of European newts.

PMID- 18624570
TI  - Spatiotemporal variation in avian diversity and the short-term effects of
      typhoons in tropical reef-karst forests on Taiwan.
AB  - The diversity and spatiotemporal variation of avifauna in different settings of
      tropical coral reef-karst forests on the Hengchun Peninsula, Taiwan, were
      examined. The short-term effects on bird assemblages following two typhoons that
      severely impacted Hengchun were investigated. Line-transect census recorded 46
      species of birds, dominated by forest-associated gleaning insectivores or
      omnivores, and 13% of the endemics of Taiwan. Prior to the typhoons, the
      continuous-canopy forest was close to the open forest setting in species
      evenness, but the species heterogeneity was lower and more variable. The
      continuous-canopy and open forests differed in overall avian composition, whereas
      two continuous-canopy forest settings were similar in composition. Typhoons did
      not significantly lower the mean numbers of either species or birds, nor affect
      the pattern of their spatial distribution in the forest settings. However, they
      did increase similarities in the species composition between the open and
      continuous-canopy settings, and caused a decrease in the similarity between
      forest edges and interiors. Overall, typhoons affected species composition more
      in the continuous-canopy forests than in the open setting, and more in interiors
      than in forest edges. This pattern corresponded to an increase in the species
      heterogeneity and species evenness in the forest interiors, indicating movements
      of birds from the edge toward the interior. Among different functional groups,
      gleaning omnivores tended to retain a pattern of higher abundance in the open
      forest setting than in the continuous-canopy forests, whereas the abundances of
      gleaning insectivores and cavity-nesting frugivores tended to decline in the
      latter or both settings.

PMID- 18624571
TI  - Gene structure and functional characterization of growth hormone in dogfish,
      Squalus acanthias.
AB  - Dogfish (Squalus acanthias) growth hormone (GH) was identified by cDNA cloning
      and protein purification from the pituitary gland. Dogfish GH cDNA encoded a
      prehormone of 210 amino acids (aa). Sequence analysis of purified GH revealed
      that the prehormone is composed of a signal peptide of 27 aa and a mature protein
      of 183 aa. Dogfish GH showed 94% sequence identity with blue shark GH, and also
      showed 37-66%, 26%, and 48-67% sequence identity with GH from osteichtyes, an
      agnathan, and tetrapods. The site of production was identified through
      immunocytochemistry to be cells of the proximal pars distalis of the pituitary
      gland. Dogfish GH stimulates both insulin-like growth factor-I and II mRNA levels
      in dogfish liver in vitro. The dogfish GH gene consisted of five exons and four
      introns, the same as in lamprey, teleosts such as cypriniforms and siluriforms,
      and tetrapods. The 5'-flanking region within 1082 bp of the transcription start
      site contained consensus sequences for the TATA box, Pit-1/GHF-1, CRE, TRE, and
      ERE. These results show that the endocrine mechanism for growth stimulation by
      the GH-IGF axis was established at an early stage of vertebrate evolution, and
      that the 5-exon-type gene organization might reflect the structure of the
      ancestral gene for the GH gene family.

PMID- 18624572
TI  - Application of RNAi technology to the inhibition of zebrafish GtHalpha, FSHbeta,
      and LHbeta expression and to functional analyses.
AB  - Zebrafish (Danio rerio) were used as a model fish, and the technique of RNA
      interference (RNAi) was employed to knockdown three subunits of the gonadotropin
      alpha (GtHalpha, common alpha), follicle-stimulating hormone beta (FSHbeta), and
      luteinizing hormone beta (LHbeta) genes. Three short-hairpin RNA (shRNA)
      expression vectors and three mismatched shRNA expression vectors as controls for
      each subunit gene were constructed, and the depression efficiency was tested in
      vivo by microinjection; the RNA or protein expression levels of the GtH genes
      were monitored by RT-PCR, Southern blotting, and green fluorescent protein (GFP)
      analyses. Expression of GtH mRNA was obviously and more efficiently depressed by
      GtHalpha RNAi expression compared with the other two subunits. A GtHalpha
      morpholino analysis showed that the GtHalpha morpholino led to suppression of
      embryonic development and the production of embryonic mutants as a result of an
      injection of GtHalpha -shRNA. Taken together, these results show that GtHalpha
      shRNA, which more efficiently targets RNAi, may have an essential role in the
      further development of sterility technology of transgenic fish for biosafety
      purposes.

PMID- 18624573
TI  - Formation and ossification of limb elements in Trachemys scripta and a discussion
      of autopodial elements in turtles.
AB  - Though sequences of formation and ossification of bony elements have been
      described for many taxa, controversy surrounds the formation of limb elements in
      turtles. Three hypotheses for patterns of formation of autopodial elements have
      been proposed, differing primarily in the origin of Distal Carpal/Tarsal 3, the
      digital arch, and Centrale 4. Patterns of formation and ossification of limb
      elements are described for Trachemys scripta. These patterns are compared to
      similar data for representatives of four families of turtles (Cheloniidae,
      Chelydridae, Emydidae, and Trionychidae). Hypotheses of limb formation are
      compared in the context of new and published data. Three species (Trachemys
      scripta, Chrysemys picta, and Chelydra serpentina) suggest that Distal Carpal 3
      forms by branching from the ulnare, whereas Distal Carpal 3 may branch from
      Distal Carpal 4 in Macrochelys temminckii and Chelonia mydas; data from Graptemys
      nigrinoda, Apalone spinifera, and Eretmochelys imbricata did not provide evidence
      for the origin of Distal Carpal 3. Centrale 4 was not observed to branch from the
      ulnare and apparently arises by de-novo condensation. Distal Carpal 4 did not
      branch from Centrale 4 in any species. Until the developmental origins of Distal
      Carpal 3 and Centrale 4 are understood, interspecific variation in the origin of
      these elements remains, and may explain some of the observed differences. Trends
      of ossification in the fore- and hind limb autopodium also are summarized.
      Homology of elements in pedal Digit V is discussed, and we suggest that the
      hooked proximal element of this digit be recognized as Distal Tarsal 5.

PMID- 18624574
TI  - Morphological characteristics of the lateral line receptors of Hynobius leechii
      (Urodela: Hynobiidae).
AB  - Morphological characteristics of the lateral line receptors, specifically the
      superficial neuromast, the pit organ, and the ampullary organ, are described and
      compared among larval, metamorphosed, and both female and male adult Hynobius
      leechii. The distribution and morphologies of the lateral line receptors are
      similar to those of other urodeles. During the transition from a larval to an
      adult salamander, the number of receptors is generally reduced, but their sizes
      increase. Other morphological changes also occur, such as the development of a
      more distinct mantle cell boundary at the epidermal surface of the adult
      ampullary and pit organs. In particular, we found kinocilia on the sensory hair
      cells of the ampullary organs of both larval and adult salamanders, and, for the
      first time, we describe two different morphologies of the pit organ in urodeles.
      The detailed description of the pit organ represents only the second study of its
      kind in urodeles. However, our comparison of lateral line receptors between
      larval and adult salamanders is the first of its kind for salamanders that
      utilize external fertilization.

PMID- 18624575
TI  - Rearing under different conditions results in different functional recoveries of
      giant interneurons in unilaterally cercus-ablated crickets, Gryllus bimaculatus.
AB  - The effects of rearing conditions on the functional recovery of wind-sensitive
      giant interneurons (GIs) after unilateral cercal ablation were investigated in
      the cricket, Gryllus bimaculatus. Crickets were reared in a glass vials to
      prohibit free walking for 14 days after unilateral cercal ablation ("14-day vial"
      crickets). Other crickets were reared in an apparatus called a "walking inducer"
      (WI) to increase the walking distance during the same 14-day period ("14-day WI"
      crickets). In these crickets, the response properties of GIs 8-1, 9-1, 9-2, and 9
      3 to air currents from various directions were investigated. From the intensity
      response curves obtained, directionality curves expressed in terms of threshold
      velocity and response magnitude were made independently. To understand changes in
      the functional recovery of GIs more thoroughly, the directional characteristics
      of GIs in crickets 1 day after unilateral cercal ablation ("1-day free" crickets)
      were also compared. Between the 1-day free and 14-day vial crickets, all the GIs
      showed differences in both threshold velocity and response magnitude for some
      stimulus directions. Between the 14-day vial and 14-day WI crickets, differences
      in the threshold velocities of GIs 9-1, 9-2, and 9-3, and in the response
      magnitudes of GIs 8-1, 9-1, and 9-3 were detected. Because the rearing condition
      after unilateral cercal ablation largely affects the compensatory recovery in
      some parameters of wind-evoked escape behavior, such as relative occurrence and
      escape direction, we discuss the functional differences in GIs revealed here in
      relation to the roles of GIs in the neural system that controls escape behavior.

PMID- 18624576
TI  - New insights into the evolution of intronic sequences of the beta-fibrinogen gene
      and their application in reconstructing mustelid phylogeny.
AB  - Mustelidae is the largest and most diverse family in the order Carnivora. The
      phylogenetic relationships among the subfamilies have especially long been a
      focus of study. Herein we are among the first to employ two new introns (4 and 7)
      of the nuclear beta-fibrinogen gene to clarify these enigmatic problems. In
      addition, two previously available nuclear (IRBP exon 1 and TTR intron 1) and one
      mt (ND2) data sets were also combined and analyzed simultaneously with the newly
      obtained sequence data in this study. Detailed characterizations of the two
      intronic regions not only reveal the remarkable occurrences of short interspersed
      element (SINE) insertion events, providing a new example supporting the
      attractive hypothesis that attrition of an earlier retroposition may offer a
      proper environment for successive retropositions by forming a "dimer-like"
      structure, but also demonstrate their utility in the resolution of mustelid
      phylogeny. All of our analyses confirm the assemblage of Mustelinae, Lutrinae,
      and Melinae with confidence; moreover, two clades within Mustelinae were clearly
      recognized, i.e., genera Mustela and Martes. Notably, genus Martes of Mustelinae
      was found to branch off first, followed by Melinae and then a clade containing
      Lutrinae and genus Mustela of Mustelinae, indicating paraphyly of Mustelinae. In
      addition, Mephitinae diverges before the other mustelids and the monophyletic
      Procyonidae in all cases, supporting its elevation to a separate family.
      Additional independent genetic markers are still in need to resolve the
      trichotomy among Mephitinae and the other two carnivoran clades, Ailuridae and
      Procyonidae/non-mephitine Mustelidae.

PMID- 18624577
TI  - Revision of the genus Miridiba Reitter, 1901 (Coleoptera, Scarabaeidae,
      Melolonthinae).
AB  - The genus Miridiba is here reviewed on the basis of external morphological and
      genital characters. This genus now contains 27 species, eight of which are new
      transfers from Holotrichia Hope, 1837; Holotrichia (Pledina) ; Melolontha
      Fabricius, 1775; and Neodontocnema . A type series of thirteen species is
      designed. Hippotrichia and Neodontocnema are described in detail.

PMID- 18624578
TI  - Karyotypes of three rat species (Mammalia: Rodentia: Muridae) from Hainan Island,
      China, and the valid specific status of Niviventer lotipes.
AB  - The karyotypes of three rat species from Hainan Island, China, were examined.
      Niviventer fulvescens (Gray, 1847) had 2n=46 and FN=64, similar to the karyotypes
      reported for N. fulvescens from Southeast Asia, while Niviventer lotipes () had
      2n=52 and FN=66, which is distinct from the known karyotypes of other Niviventer
      species. Niviventer lotipes was recently considered conspecific with N. tenaster
      (), but the two were found to have extremely different karyotypes (2n=52 and
      FN=66 in N. lotipes; 2n=46 and FN=54 in N. tenaster). Therefore, in this paper N.
      lotipes is considered a valid species for the first time; it is distinct from N.
      tenaster and endemic to Hainan Island, where N. lotipes is differentiated from N.
      fulvescens by larger body and skull sizes, a shorter tail, and darker coloration.
      Rattus nitidus (Hodgson, 1845) from Hainan Island had 2n=42 and FN=62, which is
      similar to the reported karyotypes of conspecific populations in Southeast Asia.

PMID- 18624579
TI  - Chronic toxicity of the synthetic hormone 17alpha-ethinylestradiol to Chironomus
      tentans and Hyalella azteca.
AB  - The chronic toxicity of the synthetic hormone 17alpha-ethinylestradiol (EE2) was
      investigated in two benthic invertebrates, the midge Chironomus tentans and the
      freshwater amphipod Hyalella azteca, in life-cycle water-only assays. In C.
      tentans, a 50% decrease in emergence was observed at a concentration of 1.5 mg/L;
      emergence was a more sensitive endpoint than survival, growth, or biomass.
      Reproduction was not significantly affected by EE2 exposure until a concentration
      of 3.1 mg/L, where emergence, and therefore reproduction, did not occur. In
      contrast, reproduction was the most sensitive endpoint in H. azteca (50% decrease
      in reproduction observed at a concentration of 0.36 mg/L). The sensitivity of the
      F1 generation to EE2 was also investigated with H. azteca, but was not different
      from the F0 generation. The data from the present study were combined with those
      from previous 10-d toxicity assays, to derive acute to chronic toxicity ratios
      (ACRs) for EE2. The ACRs calculated for EE2 were 13 for C. tentans and 16 for H.
      azteca, indicating that the application factors currently used in ecological risk
      assessment for the derivation of chronic toxicity are protective and conservative
      for these organisms. The results of the present study suggest that chronic
      toxicity was not mediated by disruption of endocrine pathways. Using a hazard
      quotient approach, the risk associated with sublethal exposure to EE2 was <<1 for
      H. azteca and C. tentans, indicating that adverse effects are not expected, and
      that environmental exposure to EE2 likely poses a low risk to benthic
      invertebrates.

PMID- 18624580
TI  - Does subcellular distribution in plants dictate the trophic bioavailability of
      cadmium to Porcellio dilatatus (Crustacea, Isopoda)?
AB  - The present study examined how subcellular partitioning of Cd in plants with
      different strategies to store and detoxify Cd may affect trophic transfer of Cd
      to the isopod Porcellio dilatatus. The plant species used were Lactuca sativa, a
      horticultural metal accumulator species; Thlaspi caerulescens, a herbaceous
      hyperaccumulator species; and the nonaccumulator, T. arvense. Taking into account
      that differences in subcellular distribution of Cd in plants might have an
      important role in the bioavailability of Cd to a consumer, a differential
      centrifugation technique was adopted to separate plant leaf tissues into four
      different fractions: cell debris, organelles, heat-denatured proteins, and heat
      stable proteins (metallothionein-like proteins). Plants were grown in replicate
      hydroponic systems and were exposed for 7 d to 100 microM Cd spiked with 109Cd.
      After a 14-d feeding trial, net assimilation of Cd in isopods following
      consumption of T. caerulescens and T. arvense leaves reached 16.0 +/- 2.33 and
      21.9 +/- 1.94 microg/g animal, respectively. Cadmium assimilation efficiencies
      were significantly lower in isopods fed T. caerulescens (10.0 +/- 0.92%) than in
      those fed T. arvense (15.0 +/- 1.03%). In further experiments, Cd assimilation
      efficiencies were determined among isopods provided with purified subcellular
      fractions of the three plants. On the basis of our results, Cd bound to heat
      stable proteins was the least bioavailable to isopods (14.4-19.6%), while Cd
      bound to heat-denatured proteins was the most trophically available to isopods
      (34.4-52.8%). Assimilation efficiencies were comparable in isopods fed purified
      subcellular fractions from different plants, further indicating the importance of
      subcellular Cd distribution in the assimilation. These results point to the
      ecological relevance of the subcellular Cd distribution in plants, which directly
      influence the trophic transfer of Cd to the animal consumer.

PMID- 18624581
TI  - Race and gender matter: a multidimensional approach to conceptualizing and
      measuring stress in African American women.
AB  - Based on prior research and theory, the authors constructed a multidimensional
      model of stress in African American women comprised of race-related, gender
      related, and generic stress. Exposure to and appraisal of these three types of
      stress were combined into a higher-order global stress factor. Using structural
      equation modeling, the fit of this stress factor and its ability to predict
      distress symptoms were examined in 189 socioeconomically diverse African American
      women aged 21 to 78. Results support the multidimensional conceptualization and
      operationalization of stress. Race-related, gender-related, and generic stress
      contributed equally to the global stress factor, and global stress predicted a
      significant amount of variance in distress symptoms and intensity. This model
      exhibited better fit than a model without a global stress factor, in which each
      stress component predicted distress directly. Furthermore, race-related, gender
      related, and generic stress did not contribute to distress beyond their
      representation in the global stress factor. These findings illustrate that stress
      related to central elements of identity, namely race and gender, cohere with
      generic stress to define the stress experience of African American women.

PMID- 18624582
TI  - The influence of coping styles on mammography screening in a multiethnic sample.
AB  - A total of 308 women from seven ethnic subpopulations (comprising major ethnic
      groups of Black, Hispanic, and non-Hispanic White) were interviewed to examine
      their coping styles in response to an imagined breast cancer diagnosis and to
      determine relationships among ethnicity, access to mammography, coping styles,
      and mammography screening. There were ethnic subpopulation differences in the
      five coping styles identified (problem solving, social support, positive
      reframing, wishful thinking, and avoidance), and in the relations between
      screening rates and coping styles. Specifically, ethnicity differentially
      moderated the relationship between screening rates and avoidance within and
      between major groups. Researchers studying behavior that is likely to be impacted
      by culture, such as health preventive behaviors, are well advised to take coping
      styles into account, as well as to examine potential ethnic subpopulation
      differences.

PMID- 18624583
TI  - The role of attitudinal familism in academic outcomes: a study of urban, Latino
      high school seniors.
AB  - The aim of this study was to examine the role of attitudinal familism on Latino
      high school students' academic grades, effort, motivation, and truancy. Results
      in this study reveal that having high attitudinal familism predicts fewer classes
      missed and greater academic effort. Also, when mothers' educational level is low,
      attitudinal familism is positively associated to students' academic grades. This
      study underscores the need for additional research on cultural measures that can
      help us better understand Latino adolescents' educational experiences.

PMID- 18624584
TI  - Examining cultural socialization within African American and European American
      households.
AB  - This preliminary study explored the cultural socialization processes of 227
      African American and European American parents of elementary schoolchildren. The
      Cultural Value Socialization Scales (K. M. Tyler, A. W. Boykin, C. M. Boelter, &
      M. L. Dillihunt, 2005) were used to garner parents' reports of their cultural
      value socialization activities at home. The scales contained written vignettes
      depicting persons involved in activity that reflected a specific cultural value.
      Ethnocultural values examined were communalism, verve, movement, and affect, and
      mainstream cultural values included individualism, competition, bureaucracy, and
      materialism. Regression analyses reveal that being an African American parent was
      predictive of competition and materialism scores. Race was not a significant
      predictor of the remaining cultural value socialization scores. Limitations to
      the study are discussed.

PMID- 18624585
TI  - Asian values and perceptions of intergenerational family conflict among Asian
      American students.
AB  - This investigation explores the perceptions of intergenerational family conflict
      among 93 Asian American college students from immigrant families in relation to
      reported discrepancies in Asian values with their parents, behavioral
      acculturation, gender, and ethnicity (Chinese and Korean). The study is unique in
      its examination of parent gender and specific dimensions of Asian values as
      predictors of perceived parent-child conflict. The findings indicated that as
      discrepancies in Asian values with either parent increased, reports of parent
      child conflict also increased. Values discrepancies, but not behavioral
      acculturation, were significantly associated with perceived family conflicts.
      Independent hierarchical regression models revealed a significant association
      between conflict ratings and values discrepancies with mothers on the dimension
      of Conforming to Family Norms, and with fathers on the dimension of
      Education/Career Issues. However, interaction effects within a combined model to
      test beta coefficients differences between parents were not significant. Results
      also suggest that intergenerational conflict may be associated with discrepancy
      on Respecting Elders. Implications and limitations of these findings are
      discussed.

PMID- 18624586
TI  - Cultural influences on willingness to seek treatment for social anxiety in
      Chinese- and European-heritage students.
AB  - We examined culture-related influences on willingness to seek treatment for
      social anxiety in first- and second-generation students of Chinese heritage
      (Ns=65, 47, respectively), and their European-heritage counterparts (N=60).
      Participants completed measures that assessed their willingness to seek treatment
      for various levels of social anxiety. Results showed that participants were
      similar on willingness to seek treatment at low- and high-severity levels of
      social anxiety; however, at moderate levels, first-generation Chinese
      participants were significantly less willing to seek treatment compared to their
      European-heritage counterparts. The reluctance of first-generation Chinese
      participants to seek treatment was associated with greater Chinese-heritage
      acculturation, and was not related to perceiving symptoms of social anxiety as
      less impairing. The findings support the general contention that Asians in North
      America tend to delay treatment for mental health problems.

PMID- 18624587
TI  - Subjective well-being in urban adolescents of color.
AB  - Relationships among predictors and criteria of subjective well-being were
      examined in a sample of 151 urban adolescents of color, ages 12-15. The relative
      strengths of family, peer, and school-related support and esteem in predicting
      three measures of subjective well-being (life satisfaction, positive affect, and
      negative affect) were explored. Results suggested that sense of worth in one's
      family explained a significant amount of variance in subjective well-being
      variables, above and beyond the contributions of individual, school, and peer
      related variables. Implications for prevention and mental health promotion with
      urban adolescents of color are discussed based on these findings.

PMID- 18624588
TI  - Individual and group CBT and IPT for Puerto Rican adolescents with depressive
      symptoms.
AB  - This study compared individual (I) to group (G) formats of cognitive-behavioral
      therapy (CBT) and interpersonal psychotherapy (IPT) for the treatment of
      depression in adolescents. One hundred and 12 Puerto Rican adolescents were
      randomized to four conditions (CBT-I, CBT-G, IPT-I, IPT-G). Participants were
      assessed at pretreatment and posttreatment with structured interviews to
      establish diagnosis and with self-report measures to assess treatment outcome.
      The results suggest that CBT and IPT are robust treatments in both group and
      individual formats. However, CBT produced significantly greater decreases in
      depressive symptoms and improved self-concept than IPT. The implications of these
      findings are discussed.

PMID- 18624589
TI  - Acculturation, social connectedness, and subjective well-being.
AB  - This study examined social connectedness in mainstream society as a mediator
      between acculturation and subjective well-being (SWB), and social connectedness
      in the ethnic community as a mediator between enculturation and SWB. Survey data
      from 188 Korean immigrants in the Midwest were subject to path analyses. Results
      partially supported the study hypotheses. Social connectedness in mainstream
      society tended to partially mediate the relationship between acculturation and
      SWB although the standardized mediating effect did not reach statistical
      significance. Social connectedness in the ethnic community fully mediated the
      relationship between enculturation and SWB. About 49% of the variance in SWB was
      explained by acculturation, social connectedness in the ethnic community, and
      social connectedness in mainstream society, in a descending order of their unique
      contribution. Implications for theory, research, and practice are discussed.

PMID- 18624590
TI  - Correlates of relationship, psychological, and sexual behavioral factors for HIV
      risk among Indian women.
AB  - The rate of HIV/AIDS among women in India is expected to rise yet few studies
      have examined factors related to HIV risk among Indian women. The objective of
      this prospective, cross-sectional study was to characterize similarities and
      differences in the relationships, psychological well-being, and sexual behaviors
      among Indian women (N=459). Both HIV positive (N=216) and negative (N=243) women
      from urban and rural areas in India were included in this study. Chi-square,
      analysis of variance, and logistic regression analyses revealed that in both
      geographic groups, HIV-positive women were significantly more likely to report
      marital dissatisfaction, a history of forced sex, domestic violence, depressive
      symptoms and husband's extra marital sex when compared to the HIV-negative women.
      Findings also indicate that specific factors related to the quality of the
      marital relationship such as domestic violence, martial dysfunction, and
      depressive symptoms may be related to HIV-related risks for women. Implications
      for future research and culturally relevant interventions are discussed.

PMID- 18624591
TI  - Adolescent alcohol use in context: the role of parents and peers among African
      American and European American youth.
AB  - African American youth are less likely to use alcohol than their European
      American counterparts; however, the greater consequences of use for African
      American youth highlight the need for greater research attention to this group.
      Two social contexts that have been linked with adolescent alcohol use are parents
      and peers, yet these studies have rarely included African American youth or
      failed to examine potential racial differences. This study examined the main and
      interactive effects of parents and peers, as well as the moderating role of race
      on alcohol use, in African American and European American rural adolescents
      (n=71) identified as at high-risk for alcohol use. Contrary to study hypotheses,
      however, parents were not a more robust moderator for African American than
      European American youth. Clinical implications for prevention and intervention
      programming for both African American and European American youth are discussed.

PMID- 18624592
TI  - Optimizing the effects of stress management interventions in HIV.
AB  - Scott-Sheldon, Kalichman, Carey, and Fiedler (2008) present a thoughtful,
      important, and timely meta-analysis of randomized controlled trials of stress
      management interventions in HIV. They differentiate controlled effect sizes
      across classes of acute outcomes including psychological distress, psychosocial
      processes, biological processes (immune status, viral, and hormonal) and fatigue.
      The authors join Scott-Sheldon et al., in considering future directions for this
      type of clinical psychosocial intervention research in HIV. Recommendations for
      addressing the high prevalence of psychosocial problems including diagnosable
      mental health disorders comorbid with HIV are presented. Suggestions for
      addressing medication adherence and accommodating interventions with concomitant
      substance use treatment are also considered. These recommendations are presented
      with an emphasis on expanding both the efficacy and effectiveness of psychosocial
      interventions in HIV. These recommendations are presented as realistic strategies
      for improving the modest treatment effect sizes for psychosocial outcomes and
      identifying meaningful effects on distal physiological outcomes associated with
      traditional stress management interventions in HIV.

PMID- 18624593
TI  - Clinical events in coronary patients who report low distress: adverse effect of
      repressive coping.
AB  - OBJECTIVE: Coronary artery disease (CAD) patients who report low distress are
      considered to be at low psychological risk for clinical events. However, patients
      with a repressive coping style may fail to detect and report signals of emotional
      distress. The authors hypothesized that repressive CAD patients are at risk for
      clinical events, despite low self-rated distress. DESIGN: This was a prospective
      5- to 10-year follow-up study, with a mean follow-up of 6.6 years. At baseline,
      731 CAD patients filled out Trait-Anxiety (distress), Marlowe-Crowne
      (defensiveness), and Type D scales; 159 patients were classified as "repressive,"
      360 as "nonrepressive," and 212 as "Type D." MAIN OUTCOME MEASURES: The primary
      endpoint was a composite of total mortality or myocardial infarction (MI); the
      secondary endpoint was cardiac mortality/MI. RESULTS: No patients were lost to
      follow-up; 91 patients had a clinical event (including 35 cardiac death and 32
      MI). Repressive patients reported low levels of anxiety, anger and depression at
      baseline, but were at increased risk for death/MI (21/159 = 13%) compared with
      nonrepressive patients (22/360 = 6%), p = .009. Poor systolic function, poor
      exercise tolerance, 3-vessel disease, index MI and Type-D personality--but not
      depression, anxiety or anger--also independently predicted clinical events. After
      controlling for these variables, repressive patients still had a twofold
      increased risk of death/MI, OR = 2.17, 95% CI = 1.10-4.08, p = .025). These
      findings were replicated for cardiac mortality/MI. CONCLUSION: CAD patients who
      use a repressive coping style are at increased risk for clinical events, despite
      their claims of low emotional distress. This phenomenon may cause an
      underestimation of the effect of stress on the heart. (PsycINFO Database Record
      (c) 2008 APA, all rights reserved).

PMID- 18624595
TI  - Psychosocial factors in heart surgery: presurgical vulnerability and postsurgical
      recovery.
AB  - OBJECTIVE: Distress and low perceived social support were examined as indicators
      of psychosocial vulnerability in patients about to undergo heart surgery. DESIGN:
      A total of 550 study patients underwent heart surgeries, including bypass
      grafting and valve procedures. Psychosocial interviews were conducted about five
      days before surgery, and biomedical data were obtained from hospital records.
      MAIN OUTCOME MEASURES: Sociodemographic, personality, religious, and biomedical
      factors were evaluated as predictors of psychosocial vulnerability, and all five
      sets of variables were evaluated as contributors to hospital length of stay
      (LOS). RESULTS: Patients scoring higher on one or more indicator of presurgical
      psychosocial vulnerability were younger, more likely to be female, less likely to
      be married, less well educated, lower in dispositional optimism, higher in trait
      anger, and lower in religiousness. Older age, depression, low support, and low
      trait anger each showed an independent, prospective association with greater LOS,
      and several other predictors had prospective relationships with LOS that were
      statistically mediated by depression or perceived support. CONCLUSION: Evidence
      that multiple psychosocial factors may influence adaptation to heart surgery has
      implications for understanding and ameliorating presurgical distress and for
      improving postsurgical recovery.

PMID- 18624596
TI  - What role do lay beliefs about hypertension etiology play in perceptions of
      medication effectiveness?
AB  - BACKGROUND: Some people take the disease label "hypertension" literally; leading
      to the belief that increasing relaxation instead of medication is the best
      treatment for this condition. We experimentally tested the effect of such
      underlying beliefs on ratings of interventions for hypertension and compared
      alternative communication strategies to increase medication effectiveness
      ratings. METHODS: Outpatients (N = 152) with a known diagnosis of hypertension
      read a vignette describing an asymptomatic condition and recommended treatment.
      Experimental factors were the disease label (Hypertension vs. Korotkoff's
      Syndrome) and type of argument designed to persuade the reader that medication is
      most effective (Causal vs. Correlational). MEASURES: Background measures included
      demographics, beliefs that stress causes health problems and trust in physicians.
      Outcomes were effectiveness ratings for interventions to treat the condition.
      RESULTS: Participants who read a vignette describing "Hypertension" rated
      "relaxing more" as significantly more effective than participants exposed to the
      same condition but with the unfamiliar "Korotkoff's Syndrome" label, [F(1, 141) =
      5.22, p = .024]. However, medication, reducing salty foods and losing weight were
      rated as more effective than relaxing more. Intervention ratings did not differ
      by type of argument presented. There was a significant interaction of disease
      label and trust in physicians [F(1, 125) = 7.01, p = .009]. Individuals with low
      trust rated medication as significantly less effective when exposed to an
      unfamiliar disease label. CONCLUSIONS: This study confirms the effect of the
      hypertension disease label on ratings of different interventions for the
      condition. However, participants rated biomedically recommended interventions as
      more effective than those not endorsed.

PMID- 18624597
TI  - Blood donation is an act of benevolence rather than altruism.
AB  - OBJECTIVES: Blood donation is described as an archetypal altruistic behavior, and
      recruitment/retention campaigns emphasize altruism. Here, a benevolence
      hypothesis for blood donation (both the donor and recipient benefit) rather than
      the altruism hypothesis (only the recipient gains) is proposed. DESIGN: Three
      United Kingdom-based studies contrasted benevolence and altruism: (a) a 6-month
      prospective study of blood donor behavior (Study 1: N = 957), (b) a cross
      sectional study of blood donors' intentions (Study 2: N = 333), and (c) an
      experimental study examining the effect of benevolent and altruistic messages on
      willingness to help across high- and low-cost helping behaviors for committed and
      noncommitted blood donors (Study 3: N = 200). MAIN OUTCOME: Donor behavior and
      intentions-willingness. MEASURES: Beliefs in personal and societal benefit (Time
      1) and actual donations (Time 2) were assessed in Study 1; beliefs in
      benevolence, altruism, hedonism, and kinship along with donation intentions were
      assessed in Study 2; and empathy, donor commitment, and willingness to donate
      blood, money, fund-raise, and staff a telephone helpline were assessed in Study
      3. RESULTS: Beliefs in personal rather than societal benefit predicted actual
      future donation. A path model showed that only beliefs in benevolence were
      associated with intentions to donate. Committed blood donors were more willing to
      donate blood when exposed to a benevolent message rather than an altruistic one.
      This effect was not observed for other forms of helping. CONCLUSIONS: The
      benevolence hypothesis is supported, suggesting that blood donor motivation is
      partly selfish. Blood donation campaigns should focus on benevolent rather than
      purely altruistic messages.

PMID- 18624598
TI  - Correlates and predictors of HIV risk among inner-city African American female
      teenagers.
AB  - OBJECTIVE DESIGN: For human immunodeficiency virus (HIV)-related prevention
      initiatives to be most effective, they should be broad-based and incorporate
      multiple domains of influence. This study tested how several ecodevelopmental
      domains influenced HIV-risk related attitudes and behaviors in a community sample
      of African American female teens (N = 242). MAIN OUTCOME MEASURES: Outcome
      measures were number of partners, frequency of intercourse, number of
      pregnancies, abstinence/condom use, HIV/AIDS-related attitudes and behaviors, and
      HIV testing. RESULTS: Structural Equation Modeling revealed many direct paths
      from ecodvelopmental domains to risky sexual behaviors. The findings include
      having more partners was associated with parental alcohol-related problems, more
      drug use, and a younger age at first intercourse. More frequent intercourse was
      associated with less cultural pride and more drug use. More pregnancies were
      related to a younger age at first intercourse and parental alcohol problems. HIV
      testing was associated with having experienced sexual abuse, an older age at
      first intercourse, and stronger self-efficacy. CONCLUSIONS: Prevention programs
      that focus on risk reduction could expand their focus beyond sexual behavior to
      include a broad-range of psychosocial domains that are associated with HIV-risk.
      The effectiveness of prevention programs should be monitored carefully for
      appropriateness in different ethnic groups.

PMID- 18624599
TI  - A music-based HIV prevention intervention for urban adolescents.
AB  - OBJECTIVE: This research examines the process of conducting and evaluating a
      music-based HIV prevention intervention among urban adolescents, and is informed
      by the information, motivation, behavioral skills (IMB) model. DESIGN: Musically
      talented opinion leaders were recruited to write, record, and distribute HIV
      prevention themed music to their peers to increase HIV prevention motivation,
      behavioral skills, and behaviors. In this 3-month field experiment, participants
      were 306 students enrolled in health classes at each of three large multiracial
      urban high schools (one treatment school; two control schools). MAIN OUTCOME
      MEASURES: Measures of HIV prevention information, motivation, behavioral skills,
      and behaviors, both pre- and postintervention. RESULTS AND CONCLUSION: Results
      indicate that the intervention influenced several aspects of HIV prevention
      motivation, behavioral skills, and condom use and HIV testing behaviors. This
      research demonstrates that the incorporation of music into HIV prevention
      interventions for adolescents has the potential to be effective.

PMID- 18624601
TI  - Self-efficacy as a health-protective resource in teachers? A biopsychological
      approach.
AB  - OBJECTIVE: To examine the psychobiological correlates of self-efficacy in
      teachers. DESIGN: Study 1 examined associations between teacher self-efficacy and
      cardiac activation on a working day and Study 2 assessed the cortisol morning
      response in teachers with varying levels of teacher self-efficacy. MAIN OUTCOME
      MEASURES: Teacher self-efficacy was assessed by questionnaire. In Study 1 heart
      rate, heart rate variability, and locomotor activity were recorded by 22 hours
      ambulatory monitoring and subjective measures of stress and strain were obtained.
      Study 2 assessed the cortisol response to awakening to obtain a measure of HPA
      axis activation and teachers filled in a questionnaire on physical complaints.
      RESULTS AND CONCLUSION: Study 1 found that self-efficacy proved protective for
      psychological well-being. Moreover, after controlling for locomotor activity,
      demographic, and lifestyle variables, self-efficacy was associated with elevated
      heart rate and attenuated heart rate variability during school and leisure time,
      respectively, but not during the night, thus questioning the health-implications
      of self-efficacy. Study 2 found that teachers high in self-efficacy exhibited an
      attenuated cortisol response to awakening and fewer cardiac complaints. The
      results of both studies are compatible with the view that teacher self-efficacy
      might act as a physiological toughening agent with possibly favorable health
      outcomes.

PMID- 18624602
TI  - Physical health 25 years later: the predictive ability of neuroticism.
AB  - OBJECTIVE: Neuroticism, a personality trait related to distress and emotional
      stability, is often correlated with physical symptoms and disease presence.
      Theorists have posited that chronic emotional instability creates physiological
      changes detrimental to health, yet most findings are based on cross-sectional
      analyses. The objective of the current study was to examine neuroticism assessed
      in 1973 and the likelihood of reporting physical conditions 25 years later.
      DESIGN: Participants included 21676 adult twins (n = 8143 intact twin pairs)
      ranging from 15 to 47 years old in 1973 who were assessed again between 1998 and
      2002. MAIN OUTCOME MEASURES: Thirteen physical conditions, including chronic
      fatigue syndrome, ulcers, and coronary heart disease, were selected based on
      their prior theoretical and empirical links to personality traits. RESULTS:
      Results indicate that the likelihood of having a physical condition is related to
      higher levels of prior neuroticism, with some associations attenuated when
      controlling for familial similarity. CONCLUSION: Familial influences are most
      pronounced for conditions most related to systemic pain, suggesting genetic
      pathways between neuroticism and these pain experiences.

PMID- 18624603
TI  - A taxonomy of behavior change techniques used in interventions.
AB  - OBJECTIVE: Without standardized definitions of the techniques included in
      behavior change interventions, it is difficult to faithfully replicate effective
      interventions and challenging to identify techniques contributing to
      effectiveness across interventions. This research aimed to develop and test a
      theory-linked taxonomy of generally applicable behavior change techniques (BCTs).
      DESIGN: Twenty-six BCTs were defined. Two psychologists used a 5-page coding
      manual to independently judge the presence or absence of each technique in
      published intervention descriptions and in intervention manuals. RESULTS: Three
      systematic reviews yielded 195 published descriptions. Across 78 reliability
      tests (i.e., 26 techniques applied to 3 reviews), the average kappa per technique
      was 0.79, with 93% of judgments being agreements. Interventions were found to
      vary widely in the range and type of techniques used, even when targeting the
      same behavior among similar participants. The average agreement for intervention
      manuals was 85%, and a comparison of BCTs identified in 13 manuals and 13
      published articles describing the same interventions generated a technique
      correspondence rate of 74%, with most mismatches (73%) arising from
      identification of a technique in the manual but not in the article. CONCLUSIONS:
      These findings demonstrate the feasibility of developing standardized definitions
      of BCTs included in behavioral interventions and highlight problematic
      variability in the reporting of intervention content.

PMID- 18624604
TI  - The need for integrating behavioral care in a college health center.
AB  - OBJECTIVE: A trend toward the integrated care model is evident in community
      primary medical care settings, where behavioral services are provided alongside
      medical services. The present study explored the potential need for implementing
      an integrated care model at a Midwest University Health Center by investigating
      whether the use of two behavioral questionnaires influenced providers'
      prescription of psychotropic medications and referrals for behavioral
      intervention. DESIGN: Participants were randomly assigned to condition. The 109
      participants in the experimental condition completed two behavioral
      questionnaires and the 91 control participants received treatment as usual. MAIN
      OUTCOME MEASURES: The behavioral questionnaires were the mental health-oriented
      Patient Health Questionnaire and the college-adjustment-oriented College Health
      Questionnaire. Postvisit, all participants rated their satisfaction with
      treatment; providers documented psychotropic medication prescriptions, and
      behavioral treatment referrals. RESULTS: The experimental condition displayed
      significantly higher rates of discussion of behavioral problems and prescription
      of psychotropic medications but not referrals for behavioral treatment. Patients
      in the experimental condition and all providers indicated a desire to use the
      questionnaires in future visits. CONCLUSION: The findings suggest that increased
      awareness of behavioral problems influences treatment-decision making at a
      university health service, and therefore this setting would be fertile ground for
      implementation of an integrated care model.

PMID- 18624605
TI  - Considering adaptation in preference elicitations.
AB  - OBJECTIVE: Patients with chronic health conditions usually place higher utility
      on their condition than the public does. One explanation for this discrepancy is
      that healthy people focus on the negative aspects of the condition without
      considering their own ability to emotionally adapt to the condition over time.
      The aim of this randomized experimental study was to test whether people would
      give higher utility ratings for chronic health conditions when they were
      encouraged to consider their own ability to adapt to difficult situations before
      giving their ratings. MAIN OUTCOME MEASURE: Utility ratings for four chronic
      health conditions. RESULTS: The authors presented scenarios describing 4 chronic
      health conditions to 1,117 respondents drawn from a demographically balanced U.S.
      Internet panel. The adaptation exercise did not influence respondents'
      valuations. However, utility values increasingly improved with decreasing ratings
      of how upsetting it would be to live with the condition over time. CONCLUSION:
      The authors speculate that asking people to think about adaptation changes their
      evaluations of what it would feel like to live with chronic illness, but doing so
      does not change how much they are willing to trade off to avoid that chronic
      illness.

PMID- 18624606
TI  - Nitric oxide stimulates the production of atrial natriuretic peptide and
      progesterone by human granulosa luteinized cells with an antiapoptotic effect.
AB  - OBJECTIVE: To study the effect of nitric oxide (NO) on atrial natriuretic peptide
      (ANP) and progesterone (P) production by human granulose luteinized cells (GLC)
      in vitro and to elucidate their role on the survival of cultured cells. METHODS:
      Human GLCs were cultured in HAM's F10/10% FCS as monolayers for 24 h.
      Subsequently GLCs were treated for 24 h with 0.5 mM Sodium Nitroprusside (SNP, NO
      donor) and 0.5 mM Aminoglutethimide (AG , P450scc inhibitor). The levels of ANP
      and P were measured in supernatants of cultured cells by proANP(1-98) kit and
      RIA, respectively. Caspase-3 activity was determined by Ac-DEVD-pNA as substrate.
      RESULTS: The production of ANP and P was increased by NO as compared to control
      cells (p<0.05). AG diminished the production of P compared to SNP (p<0.05). The
      caspase-3 activity was significantly lower in SNP treated cells (p<0.05) and
      increased significantly after AG treatment compared to control cells (p<0.05).
      CONCLUSION: NO generated by SNP in human GLCs culture stimulated the production
      of ANP and P. The higher levels of ANP and P were closely related to
      significantly lower caspase-3 activity thus showing the role of ANP, P and NO on
      the survival of preovulatory human follicle.

PMID- 18624607
TI  - Short-term effect of soy consumption on thyroid hormone levels and correlation
      with phytoestrogen level in healthy subjects.
AB  - OBJECTIVE: Since soy isoflavones may influence the thyroid hormone feedback
      system by interference with their biosynthesis, secretion and metabolism, we
      tested whether their controlled shortterm consumption affects thyroid function.
      METHODS: Eighty six volunteers--university students (32 males and 54 females)
      were eating unprocessed boiled natural soybeans (2 g/kg body weight/day) for 7
      consecutive days. Thyrotropin, free thyroid hormones, antibodies to thyroid
      peroxidase and to thyroglobulin, and actual levels of unconjugated major soy
      phytoestrogens, daidzein and genistein, were measured in sera collected before,
      at the end and one week after finishing soy meal consumption. RESULTS: Both
      phytoestrogens increased significantly (p<0.0001) at the end of soy-diet and fell
      down after its termination nearly back to the initial values. No significant
      changes were found in female group, while in males a significant transitory
      increase of thyrotropin (p<0.0001) was recorded. When actual levels of
      phytoestrogens were related to thyroid parameters, the only significant
      correlations were found between basal levels of daidzein and thyrotropin,
      daidzein and antithyroglobulin at the end of soy consumption in males, and
      between daidzein and free thyroxine at the end of the soy ingestion in females.
      CONCLUSION: Though only modest and transitory effects on thyroid parameters
      occurred after controlled short-term soy consumption, some actual thyroid hormone
      parameters do correlate with actual isoflavone levels.

PMID- 18624608
TI  - Inverse relationship between adiponectin and plasminogen activator inhibitor-1 in
      metabolic syndrome patients.
AB  - OBJECTIVES: To determine the serum levels of adiponectin and plasminogen
      activator inhibitor-1 in metabolic syndrome versus healthy controls and to see
      the relation of them with each other and with the metabolic syndrome components.
      METHODS: Adiponectin and plasminogen activator inhibitor-1 levels were measured
      in 53 subjects with metabolic syndrome and 30 healthy controls by ELISA. All
      subjects of metabolic syndrome had the criterias of metabolic syndrome (obesity,
      insulin resistance, hypertension, dyslipidemia, glucose metabolism disorders).
      Adiponectin and plasminogen activator inhibitor-1 levels in serum were compared
      between the groups and relations of them with each other, with metabolic syndrome
      components, also HbA1c and C peptide were examined. For statistical analysis
      student-t test and pearson's correlations were used. RESULTS: Metabolic syndrome
      group had significantly lower adiponectin and higher plasminogen activator
      inhibitor-1 levels than healthy controls (p<0.001). There was no difference
      between the average age of both groups. There was an inverse relationship between
      plasma adiponectin and plasminogen activator inhibitor-1 ( r= -0.653, p<0.001).
      Also adiponectin levels were inversely correlated with body mass index (BMI),
      waist and hip circumferences, systolic and diastolic pressures, fasting plasma
      glucose, 2 hour postprandial serum glucose, HbA1c, C peptide, triglycerides,
      total cholesterol, insulin and insulin resistance (HOMA). Plasminogen activator
      inhibitor-1 levels were correlated positively with these parameters. CONCLUSION:
      Hypoadiponectinemia and elevated plasminogen activator inhibitor-1 levels were
      closely associated with the metabolic syndrome and its components, inverse
      relationship was present between adiponectin and plasminogen activator inhibitor
      1 levels in metabolic syndrome patients. It is suggested that measuring and
      regulating the plasma concentration of adiponectin and plasminogen activator
      inhibitor-1 may be useful for management of the metabolic syndrome so this may
      prevent the development of obesity, cardiovascular diseases and diabetes.

PMID- 18624609
TI  - Protective effect of antioxidant adjuvant treatment with hormone replacement
      therapy against cardiovascular diseases in ovariectomized rats.
AB  - OBJECTIVE: Since it is well known that estrogen deficiency or ovariectomy (OVX)
      results in a reduction of sexual steroids and increased prevalence of
      cardiovascular diseases (CVD), it was aimed to assess the benefits of hormone
      replacement therapy (HRT) alone or together with antioxidant vitamins (E and C)
      for the protection against CVD and oxidative stress. METHODS: The effect of
      ovariectomy and HRT alone or combined with antioxidants (Antiox) on lipid
      metabolism, insulin sensitivity, oxidative stress, antioxidant and markers of CVD
      was examined in four groups of female Wistar rats of 10 animals each: Group 1
      (sham operated); Group 2 (OVX); Group 3 (OVX + HRT); Group 4 (OVX + HRT +
      Antiox). After four weeks of treatment total cholesterol, HDL-cholesterol (HDL
      C), LDL-cholesterol (LDL-C), triglycerides (TG), Apo B lipoprotein, glucose and
      insulin as well as malondialdehyde (MDA; as index of lipid peroxidation),
      oxidized LDL (ox-LDL), homocysteine level, oxidized and reduced glutathione were
      determined in plasma. RESULTS: The lipid pattern of OVX rats showed a deviation
      from sham group in all lipid fractions and atherogenic indexes; LDL/HDL and
      TC/HDL. HRT group showed partial correction of these abnormalities and the
      antioxidant adjunct treatment significantly improved the lipid profile. OVX rats
      had significantly higher insulin and glucose levels compared to the sham group
      which was abolished by HRT and completely normalized by adjunct antioxidant
      treatment. HOMA was significantly decreased by HRT and showed normal value with
      adjunct antioxidant treatment. The oxidative stress parameters; MDA, ox-LDL and
      GSSG levels were increased, also homocysteine was greatly elevated in OVX rats.
      The HRT significantly corrected the levels of MDA, ox-LDL and GSSG while it had
      no effect on homocysteine and GSH. The adjunct antioxidant treatment potentiated
      the HRT and showed a significant correction of homocysteine and GSH levels.
      CONCLUSION: Our data suggested that adjunct antioxidant treatment together with
      HRT may ameliorate the cardiovascular protection and improve metabolic syndrome
      as well as insulin resistance in OVX rats. Further studies are warranted to
      elucidate the beneficial role of antioxidant treatment on cardiovascular
      protection of menopause women.

PMID- 18624610
TI  - Vasopressin and oxytocin release into CSF after sympathetic stimulation in rat.
AB  - Vasopressin and oxytocin are neurohormones of the posterior pituitary lobe
      released not only into the blood, but also into cerebrospinal fluid (CSF).
      Posterior pituitary lobe has central and peripheral noradrenergic innervation;
      peripheral origins from superior cervical ganglia (SCG) (Alper et al. 1980;
      Saavedra 1986). It is known, that sympathetic nervous system is involved in
      vasopressin (AVP) and oxytocin (OXY) release from neurohypophysis into the blood
      (Romeo et al. 1991; Lipinska et al. 1996). The factors which stimulate
      neurohormones release into the blood do not always cause their release into CSF
      (Dogterom et al. 1977; Szczepanska-Sadowska et al. 1983). The aim of this study
      was to elucidate the question whether the stimulation of preganglionic fibers of
      the SCG could influence the release of AVP and OXY into CSF.

PMID- 18624611
TI  - The impact of parathyroid gland autotransplantation during bilateral thyroid
      surgery for Graves' disease on postoperative hypocalcaemia.
AB  - OBJECTIVE: The aim of this study was to compare the rate of hypocalcaemia after
      bilateral thyroid resection for Graves' Disease in patients with and without
      parathyroid gland autotransplantation (PTAT). PATIENTS AND METHODS: A total of
      153 patients following thyroid surgery for Graves' disease were studied. Patients
      were divided into three groups. Subgroup I comprised of 129 patients without
      PTAT, Subgroup II comprised of 19 patients with PTAT of one parathyroid gland and
      Subgroup III comprised of 6 patients with PTAT of two parathyroid glands.
      Association between PTAT and postoperative hypocalcaemia (PH) after thyroidectomy
      was investigated. RESULTS: There were 27/128 (21.1%) patients with transient and
      10/128 (7.8%) patients with permanent hypocalcemia within Subgroup I. Among
      Subgroup II 4/19 (21.1%) patients developed transient and no patient developed
      permanent hypocalcaemia, while in Subgroup III 2/6 (33.3 %) patients developed
      transient hypocalcaemia which became persistent. Thus, the frequency of permanent
      postthyroidectomy hypocalcaemia (PH) was significantly higher in the Subgroup III
      with PTAT of two parathyroid glands when compared to the Subgroup I without PTAT
      (p=0.032) and Subgroup II with PTAT of only one parathyroid glands (p=0.012).
      CONCLUSION: PTAT of one parathyroid gland is an effective procedure to reduce the
      incidence of permanent hypoparathyroidism after bilateral surgery for Graves
      disease. Transient hypoparathyroidism was not influenced by PTAT.

PMID- 18624612
TI  - CCLM: evolving to meet the needs of today's laboratory professionals and
      scientists.

PMID- 18624613
TI  - Rapid diagnostic tests to detect pathogenic microorganisms.

PMID- 18624615
TI  - Strategies of bacteria screening in cellular blood components.
AB  - Since the impressive reduction of transfusion-transmitted virus infections,
      bacterial infections by blood transfusion represent the most important infection
      risk. Platelet concentrates are the current focus of attention, as they are
      stored under temperature conditions which allow growth of contaminating bacteria
      up to 10(10) and more microbes per platelet bag. This paper does not consider the
      pathogen reduction methods but will assess suitable screening methods. Beside
      conventional microbiological approaches or surrogate markers, several efficient
      methods able to detect bacterial contamination in platelets are available on the
      market. They need to be divided into two different methodological principles: the
      cultivation methods and rapid methods. Cultivation or incubation methods require
      some time for signal production as they depend on growth of microbes. Thus, they
      have to be combined with early sampling, i.e., the sample to be examined has to
      be drawn from the blood component 1 day after donation. Their advantage is the
      relatively uncomplicated implementation into the logistics of blood banks.
      Because of the initially very low count of bacteria after donation, a certain
      small sampling error in application of that strategy remains. Rapid methods are
      able to produce the diagnosis within a short time. Therefore, they allow
      postponing of sample drawing, ideally up to the time immediately before
      transfusion. However, this procedure causes logistic complications. On the other
      hand, late sampling combined with a rapid method will prevent the transfusion of
      highly contaminated platelet concentrates leading to acute septic shock up to the
      death of the patient. Considering the sum of different aspects including the
      supply of patients, the potential improvement of microbial safety of platelet
      concentrates is comparable in both strategies.

PMID- 18624614
TI  - Rapid methods for diagnosis of bloodstream infections.
AB  - Direct detection technologies for pathogenic microorganisms are emerging to be
      applied in the diagnosis of serious bloodstream infections and infections at
      sterile body sites, as well as for quality control measures prior to the release
      of sterile blood products and to ascertain microbial safety of food. Standard
      blood cultures as the current gold standard for detection of bacteraemia/sepsis
      and other culture-based microbiological identification procedures are
      comparatively slow and have limited sensitivity for fastidious or slow-growing
      microorganisms. Rapid nucleic acid-based technologies with PCR amplification or
      hybridisation probes for specific pathogens, broad-range bacterial or fungal
      assays, flow cytometry, as well as protein-based characterisation by mass
      spectrometry, aim at identification of pathogenic microorganisms within minutes
      to hours. Interpretation of direct detection of panbacterial or panfungal nucleic
      acids instead of living microorganisms in blood is complex, given the risk of
      contamination, the ubiquitous presence of bacterial and fungal DNA, and the lack
      of a gold standard. Since many of the infections at sterile sites, particularly
      sepsis, are medical emergencies requiring immediate therapeutic responses, rapid
      technologies could contribute to reduction of morbidity, mortality, and of the
      economic burden. This review summarises the currently available data on rapid non
      culture-based technologies and outlines the potential clinical usefulness in
      infectious disease diagnosis.

PMID- 18624616
TI  - Methods for the detection of bacterial contamination in blood products.
AB  - Culture-based and molecular assays have been developed for the screening of
      platelet concentrates and other blood components for bacterial contaminations. In
      this review, the principles of the assays are outlined. The focus of this review
      is the assessment of the analytical qualities of the methods. Spiking studies by
      adding defined levels of a wide range of bacteria to the complex biological
      matrix provide the first basis to evaluate and compare the qualities of methods
      for bacterial detection. The sensitivity acceptable for reliable screening for
      bacteria critically depends on the timing of either early sampling (within a
      period of up to 24 h after preparation of the blood component) or late sampling
      (a few hours before issuing the blood component). Large screening studies are
      essential to confirm both adequate sensitivity and specificity of the testing. In
      the ideal setting, these studies are prospectively planned and include systematic
      surveillance of adverse events in response to the administration of the screened
      products. The findings from sterility testing (predominantly with automated
      systems for detection of bacteria based on CO(2) generation) of more than 550,000
      platelet concentrates in 13 studies are summarised. The limitations of the early
      sampling and the "negative-to-date" strategy to issue platelet concentrates are
      addressed. A few reported cases of probable transmission of bacteria by platelet
      transfusion despite negative screening tests emphasise the need to further
      develop optimised methods for testing of bacteria blood components.

PMID- 18624617
TI  - Bacteria detection by flow cytometry.
AB  - Since bacterial infection of the recipient has become the most frequent infection
      risk in transfusion medicine, suitable methods for bacteria detection in blood
      components are of great interest. Platelet concentrates are currently the focus
      of attention, as they are stored under temperature conditions, which enable the
      multiplication of most bacteria species contaminating blood donations. Rapid
      methods for bacteria detection allow testing immediately before transfusion in a
      bed-side like manner. This approach would overcome the sampling error observed in
      early sampling combined with culturing of bacteria and would, at least, prevent
      the transfusion of highly contaminated blood components leading to acute septic
      shock or even death of the patient. Flow cytometry has been demonstrated to be a
      rapid and feasible approach for detection of bacteria in platelet concentrates.
      The general aim of the current study was to develop protocols for the application
      of this technique under routine conditions. The effect of improved test reagents
      on practicability and sensitivity of the method is evaluated. Furthermore, the
      implementation of fluorescent absolute count beads as an internal standard is
      demonstrated. A simplified pre-incubation procedure has been undertaken to
      diminish the detection limit in a pragmatic manner. Additionally, the application
      of bacteria detection by flow cytometry as a culture method is shown, i.e.,
      transfer of samples from platelet concentrates into a satellite bag, incubation
      of the latter at 37 degrees C, and measuring the contaminating bacteria in a flow
      cytometer.

PMID- 18624618
TI  - Microbial safety of cell based medicinal products--what can we learn from
      cellular blood components?
AB  - Today, sterility of established parenteral drugs including biologicals, such as
      plasma derived products, is practically guaranteed. Bacterially contaminated
      products are extremely rare exceptions owing to the efficiency of the
      manufacturing processes in the pharmaceutical industry. In contrast, the
      manufacturing processes of cell based medicinal products or tissue preparations
      show much less defined conditions. The sterility of source materials cannot be
      guaranteed in many cases. As a rule, these source materials cannot be sterilised,
      as it holds true for the final products. Furthermore, the established methods for
      sterility testing are not applicable for cell preparations. Sterility of a
      restricted sample does not guarantee sterility of the whole preparation. Thus,
      small amounts of residual bacteria in the product can be overlooked and can grow
      up to enormous numbers during storage and shipping of cell based medicinal
      products. Considering these problems, there are some parallels in the warranty of
      microbial safety of cellular blood components. Therefore, the experiences
      collected in transfusion medicine in the past decade can be successfully used in
      the production of cell based medicinal products. Comparable to the situation
      regarding cellular blood components, there is a need for new principles in rapid
      bacteria detection.

PMID- 18624619
TI  - Screening for genetic heterogeneity in the interferon sensitivity determining
      region of the hepatitis C virus genome by polymerase chain reaction with melting
      curve analysis.
AB  - BACKGROUND: Although mutations in the interferon (IFN) sensitivity determining
      region (ISDR) of hepatitis C virus (HCV) have been reported to be useful as a
      predictive viral factor for IFN therapy in patients infected with HCV-1b, such
      laboratory research has not been favorably translated into the clinic. To promote
      such translation, we attempted the establishment of a rapid and simple polymerase
      chain reaction (PCR) combined with melting curve analysis (MCA) to screen for
      mutations in the ISDR and for the monitoring of HCV quasispecies. METHODS: A PCR
      MCA protocol was established using in-house primers and hybridization probes
      designed according to the results of direct sequencing of 34 HCV-1b samples.
      Then, the performance of PCR-MCA was verified by comparing with mutation profiles
      obtained by direct sequencing and sequencing after cloning. RESULTS: The MCA
      assay revealed that melting temperature (Tm) was inversely correlated with the
      number of nucleotide (nt) and amino acid substitutions in the ISDR deduced on the
      basis of the results of direct sequencing. A boundary Tm of 58.0 degrees C
      allowed us to discriminate HCV genomes into two groups: one with a Tm >58.0
      degrees C had no or a low number of nt substitutions, while the other genomes
      with a Tm <58.0 degrees C had a high number of nt substitutions, corresponding to
      wild-type in the former and mutant-type in the latter in respect of a clinical
      setting for IFN therapy. Moreover, this MCA assay provided precise discrimination
      of Tm between clones, reflecting the degree of the genetic complexity of HCV
      genomes. CONCLUSIONS: This study indicates that the MCA assay is useful to
      rapidly and simply screen the mutational status of the ISDR of HCV, as well as in
      using the ISDR as one of the targets for discriminating the genetic complexity of
      HCV genomes. The MCA assay could also be applicable as a convenient and useful
      screen of the genetic heterogeneity of clones relating to HCV quasispecies.

PMID- 18624620
TI  - Improved real-time detection of the H63D and S65C mutations associated with
      hereditary hemochromatosis using a SimpleProbe assay format.
AB  - BACKGROUND: Genetic predisposition to hemochromatosis involves several different
      point mutations in the HFE gene. Routine testing for two such mutations (H63D and
      S65C) using real-time genotyping deserves special care, as these mutations are in
      close proximity (6 bp) of each other. METHODS: A novel assay was designed for
      these two mutations based on a SimpleProbe assay format that allows for more
      flexibility in assay design, as it requires only one detection probe instead of
      the two probes that are commonly used with a hybridization probe based assay.
      RESULTS: The SimpleProbe assay format yielded data that were easily interpreted
      without significant optimizing efforts. CONCLUSIONS: The SimpleProbe assay format
      offers some unique advantages compared to hybridization probes and offers a
      robust and interesting alternative to hybridization probes in the detection of
      genetic variations. This is the first time that the use of this assay format is
      described in the clinical literature.

PMID- 18624621
TI  - Plasma interleukin-1beta, -6, -8 and tumor necrosis factor-alpha as highly
      informative markers of pelvic inflammatory disease.
AB  - BACKGROUND: The role of proinflammatory cytokines in pelvic inflammatory disease
      (PID) is unclear. We therefore determined whether plasma proinflammatory
      cytokines, interleukin-1beta (IL-1beta), IL-6, IL-8 and tumor necrosis factor
      alpha (TNF-alpha) were useful plasma markers in PID patients. METHODS: Multiplex
      bead array analysis was used to measure the plasma levels of proinflammatory
      cytokines in 50 healthy controls as well as in 41 PID patients before and after
      routine protocol treatments. RESULTS: IL-1beta, IL-6, IL-8 and TNF-alpha were
      significantly elevated in PID patients before antibiotic treatment than after
      treatment. However, IL-8 was not significantly different between healthy controls
      and PID patients. The relative increase in ratio of IL-6 was significantly
      correlated with white blood cell count (r=0.448, p=0.003), neutrophil count
      (r=0.472, p=0.002) and C-reactive protein level (r=0.412, p=0.008). CONCLUSIONS:
      IL-1beta, IL-6, IL-8 and TNF-alpha may play an important role in the pathogenesis
      of PID. These biomarkers, particularly IL-6, could be useful adjuncts for the
      clinical diagnosis of PID.

PMID- 18624622
TI  - Prohormone brain natriuretic peptide (proBNP), BNP and N-terminal-proBNP
      circulating levels in chronic hemodialysis patients. Correlation with ventricular
      function, fluid removal and effect of hemodiafiltration.
AB  - BACKGROUND: Brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP) and to
      a lesser extent prohormone proBNP are recognized as biochemical markers of left
      ventricular dysfunction. In renal failure, interpretation of natriuretic peptide
      remains unclear, as natriuretic peptide levels may be not only be dependent on
      cardiac function and dimensions but also on renal function, fluid volume and
      removal by dialysis procedure including hemodiafiltration (HDF). The purpose of
      this study was (i) to assess BNP, NT-proBNP and proBNP levels and their
      correlation with clinical and echocardiographic data in chronic hemodialysis
      patients, and (ii) to investigate basal level alteration following HDF. METHODS:
      Baseline clinical and echocardiographic parameters were collected in 31 dialysis
      patients without evidence of cardiac failure. Pre- and post-HDF BNP, NT-proBNP
      and proBNP concentrations were measured. Correlations between echocardiographic
      measurements and basal circulating peptides, between changes in peptide values
      and changes in fluid volume after HDF were investigated. RESULTS: Baseline
      plasmatic levels were elevated (BNP=517+/-840 pg/mL, NT-proBNP=5340+/-6132 pg/mL
      and proBNP=3569+/-4683 pg/mL) and correlated with left auricular diameter and
      left ventricular mass index. HDF session induced a significant decrease of 39%,
      59% and 36% for BNP, NT-proBNP and proBNP levels, respectively. This decrease was
      not correlated to post-HDF fluid removal or weight decrease. Correlation between
      BNP and proBNP was stronger (r(2)=0.88) than between NT-proBNP and proBNP
      (r(2)=0.54). CONCLUSIONS: Despite their elimination, BNP, NT-proBNP and proBNP
      could be potential markers of left ventricular remodeling in chronic renal
      failure patients on hemodialysis. According to these results, their cut-off
      values, however, need to be re-evaluated.

PMID- 18624623
TI  - A comparison of two different assays for determining S-100B in serum and urine.
AB  - BACKGROUND: Brain injury after head trauma can be detected by S-100B measurements
      in serum. Recent preliminary studies indicate that urinary levels of S-100B are
      also increased after head injury, a finding that is of possible clinical value.
      The aims of the present study are two-fold: to compare serum measurements of two
      assays, the Liaison Sangtec 100 system and the Elecsys S100 test, and to
      investigate to what extent they can detect and measure S-100B in urine. METHODS:
      A total of 191 serum and 174 urine samples from 107 patients (children aged
      between 1 and 18 years following head trauma) were measured with both assays. The
      results were compared using correlation analysis and Bland-Altman difference
      plots. RESULTS: Serum values of the Sangtec system ranged from 0.02 to 2.28
      microg/L, and from 0.005 to 2.13 microg/L for the Elecsys test. Comparisons
      showed a clear correlation (correlation coefficient 0.80) but not an agreement
      between the methods. The Sangtec system could only detect S-100B in 20 out of 174
      urine samples (range 0.02-0.06 microg/L), whereas the Elecsys test could detect S
      100B in 171 samples (range 0.005-0.14 microg/L). No clear relation was observed
      between the two methods in urine analysis (correlation coefficient 0.60).
      CONCLUSION: The Sangtec and Elecsys assays are not interchangeable methods when
      analyzing S-100B in serum or urine samples after head injury.

PMID- 18624624
TI  - Procalcitonin values in preeclamptic women are related to severity of disease.

PMID- 18624625
TI  - Cross-reactivity between lambda antiserum and fibrinogen: a double trap in
      interpretation of serum protein electrophoresis.

PMID- 18624626
TI  - Erroneous result of white blood cell differential count in a patient with mixed
      hyperlipidemia.

PMID- 18624627
TI  - Lack of association of GH T1663A variation and IGFBP3-202A/C polymorphism with
      risk of ischemic stroke in Chinese.

PMID- 18624629
TI  - HIV transmission risk behaviors among HIV-infected persons who are successfully
      linked to care.
AB  - OBJECTIVES: We examined the relationship between receipt of medical care for
      human immunodeficiency virus (HIV) infection and HIV transmission risk behavior
      among persons who had received a recent diagnosis of HIV infection. METHODS: We
      enrolled 316 participants from 4 US cities and prospectively followed up
      participants for 1 year. Generalized estimating equations were used to examine
      whether having at least 3 medical care visits in a 6-month period was associated
      with unprotected vaginal or anal intercourse with an HIV-negative partner or
      partner with unknown HIV status. RESULTS: A total of 27.5% of the participants
      (84 of 305) self-reported having unprotected sex with an HIV-negative or unknown
      status partner at enrollment, decreasing to 12% (31 of 258) and 14.2% (36 of 254)
      at 6-month and 12-month follow-ups, respectively. At follow-up, people who had
      received medical care for HIV infection at least 3 times had reduced odds of
      engaging in risk behavior, compared with those with fewer visits. Other factors
      associated with reduced risk behavior were being >30 years of age, male sex, not
      having depressive symptoms, and not using crack cocaine. CONCLUSIONS: Being in
      HIV care is associated with a reduced prevalence of sexual risk behavior among
      persons living with HIV infection. Persons linked to care can benefit from
      prevention services available in primary care settings.

PMID- 18624630
TI  - Management of Toxoplasma gondii infection during pregnancy.
AB  - Acute infection with Toxoplasma gondii during pregnancy and its potentially
      tragic outcome for the fetus and newborn continue to occur in the United States,
      as well as worldwide, despite the fact that it can be prevented. The infection
      can be acquired through ingestion of infected, undercooked meat or contaminated
      food or water. Transmission to the fetus occurs almost solely in women who
      acquire their primary infection during gestation and can result in visual and
      hearing loss, mental and psychomotor retardation, seizures, hematological
      abnormalities, hepatosplenomegaly, or death. Systematic education and serological
      screening of pregnant women are the most reliable and currently available
      strategies for the prevention, diagnosis, and early treatment of the infection in
      the offspring; this is largely because toxoplasmosis in pregnant women most often
      goes unrecognized. Treatment of the infection in the fetus and infant during the
      first year of life has been demonstrated to significantly improve the clinical
      outcome.

PMID- 18624632
TI  - Twenty years of transgenic plants resistant to Cucumber mosaic virus.
AB  - Plant genetic engineering has promised researchers improved speed and flexibility
      with regard to the introduction of new traits into cultivated crops. A variety of
      approaches have been applied to produce virus-resistant transgenic plants, some
      of which have proven to be remarkably successful. Studies on transgenic
      resistance to Cucumber mosaic virus probably have been the most intense of any
      plant virus. Several effective strategies based on pathogen-derived resistance
      have been identified; namely, resistance mediated by the viral coat protein, the
      viral replicase, and post-transcriptional gene silencing. Techniques using non
      pathogen-derived resistance strategies, some of which could offer broader
      resistance, generally have proven to be much less effective. Not only do the
      results obtained so far provide a useful guide to help focus on future
      strategies, but they also suggest that there are a number of possible mechanisms
      involved in conferring these resistances. Further detailed studies on the
      interplay between viral transgene-derived molecules and their host are needed in
      order to elucidate the mechanisms of resistance and pathogenicity.

PMID- 18624633
TI  - Roadmap to new virulence determinants in Pseudomonas syringae: insights from
      comparative genomics and genome organization.
AB  - Systematic comparison of the current repertoire of virulence-associated genes for
      three Pseudomonas syringae strains with complete genome sequences, P. syringae
      pv. tomato DC3,000, P. syringae pv. phaseolicola 1448A, and P. syringae pv.
      syringae B728a, is prompted by recent advances in virulence factor identification
      in P. syringae and other bacteria. Among these are genes linked to epiphytic
      fitness, plant- and insect-active toxins, secretion pathways, and virulence
      regulators, all reflected in the recently updated DC3,000 genome annotation.
      Distribution of virulence genes in relation to P. syringae genome organization
      was analyzed to distinguish patterns of conservation among genomes and
      association between genes and mobile genetic elements. Variable regions were
      identified on the basis of deviation in sequence composition and gaps in syntenic
      alignment among the three genomes. Mapping gene location relative to the genome
      structure revealed strong segregation of the HrpL regulon with variable genome
      regions (VR), divergent distribution patterns for toxin genes depending on
      association with plant or insect pathogenesis, and patterns of distribution for
      other virulence genes that highlight potential sources of strain-to-strain
      differences in host interaction. Distribution of VR among other sequenced
      bacterial genomes was analyzed and future plans for characterization of this
      potential reservoir of virulence genes are discussed.

PMID- 18624634
TI  - Early progress in aphid genomics and consequences for plant-aphid interactions
      studies.
AB  - Aphids occupy a niche comprising two conceptual realms: a micron-scale feeding
      site beneath the plant surface, in which a syringe-like appendage mediates
      chemical exchange with a specific plant cell type; and the larger realm of a
      metazoan with sensory organs, a nervous system, and behavior, all responsive to
      the condition of the host plant and the broader environment. The biology that
      connects these realms is not well understood, but new details are emerging with
      the help of genomic tools. The power of these tools is set to increase
      substantially now that the first genome of an aphid is being sequenced and
      annotated. This has been possible because a community of aphid researchers
      focused their efforts to develop and share genomic resources through an
      international consortium. This complete genome sequence, along with other
      resources, should permit major advances in understanding the complex and peculiar
      biological traits responsible for aphids' evolutionary success and their damaging
      effects on agriculture. This review highlights early progress in the application
      of aphid genomics and identifies key issues of plant-aphid interactions likely to
      benefit as molecular tools are further developed. Use of this new knowledge could
      make significant contributions to crop protection against these and other phloem
      feeding insects.

PMID- 18624635
TI  - Global switches and fine-tuning-ABA modulates plant pathogen defense.
AB  - Plants are obliged to defend themselves against a wide range of biotic and
      abiotic stresses. Complex regulatory signaling networks mount an appropriate
      defense response depending on the type of stress that is perceived. In response
      to abiotic stresses such as drought, cold, and salinity, the function of abscisic
      acid (ABA) is well documented: elevation of plant ABA levels and activation of
      ABA-responsive signaling result in regulation of stomatal aperture and expression
      of stress-responsive genes. In response to pathogens, the role of ABA is more
      obscure and is a research topic that has long been overlooked. This article aims
      to evaluate and review the reported modes of ABA action on pathogen defense and
      highlight recent advances in deciphering the complex role of ABA in plant
      pathogen interactions. The proposed mechanisms responsible for positive or
      negative effects of ABA on pathogen defense are discussed, as well as the
      regulation of ABA signaling and in planta ABA concentrations by beneficial and
      pathogenic microorganisms. In addition, the fast-growing number of reports that
      characterize antagonistic and synergistic interactions between abiotic and biotic
      stress responses point to ABA as an essential component in integrating and fine
      tuning abiotic and biotic stress-response signaling networks.

PMID- 18624631
TI  - Host restriction factors blocking retroviral replication.
AB  - Retroviruses are highly successful intracellular parasites, and as such they are
      found in nearly all branches of life. Some are relatively benign, but many are
      highly pathogenic and can cause either acute or chronic diseases. Therefore,
      there is tremendous selective pressure on the host to prevent retroviral
      replication, and for this reason cells have evolved a variety of restriction
      factors that act to inhibit or block the viruses. This review is a survey of the
      best-characterized restriction factors capable of inhibiting retroviral
      replication and aims to highlight the diversity of strategies used for this task.

PMID- 18624636
TI  - Virus-induced gene silencing (VIGS) as a reverse genetic tool to study
      development of symbiotic root nodules.
AB  - Virus-induced gene silencing (VIGS) can provide a shortcut to plants with altered
      expression of specific genes. Here, we report that VIGS of the Nodule inception
      gene (Nin) can alter the nodulation phenotype and Nin gene expression in Pisum
      sativum. PsNin was chosen as target because of the distinct non-nodulating
      phenotype of nin mutants in P. sativum, Lotus japonicus, and Medicago truncatula.
      The vector based on Pea early browning virus (PEBV) was engineered to carry one
      of three nonoverlapping fragments (PsNinA, PsNinB, and PsNinC) derived from the
      PsNin cDNA. Vector inoculation was mediated by agroinfiltration and, 2 weeks
      later, a Rhizobium leguminosarum bv. viceae culture was added in order to induce
      root nodulation. At this time point, it was estimated that systemic silencing was
      established because leaves of reference plants inoculated with PEBV carrying a
      fragment of Phytoene desaturase displayed photo bleaching. Three weeks after
      Rhizobium spp. application, plants inoculated with a control vector nodulated
      normally, whereas nodulation was almost eliminated in plants inoculated with a
      vector carrying PsNinA and PsNinC. For plants inoculated with a vector carrying
      PsNinB, nodulation was reduced by at least 45%. Down-regulation of PsNin
      transcripts in plants inoculated with vectors carrying PsNin cDNA fragments was
      confirmed and these plants displayed a relative increase in the root/shoot ratio,
      as expected if nitrogen fixation had been impaired.

PMID- 18624637
TI  - Tomatinase from Fusarium oxysporum f. sp. lycopersici is required for full
      virulence on tomato plants.
AB  - Saponin detoxification enzymes from pathogenic fungi are involved in the
      infection process of their host plants. Fusarium oxysporum f. sp lycopersici, a
      tomato pathogen, produces the tomatinase enzyme Tom1, which degrades alpha
      tomatine to less toxic derivates. To study the role of the tom1 gene in the
      virulence of F. oxysporum, we performed targeted disruption and overexpression of
      the gene. The infection process of tomato plants inoculated with transformants
      constitutively producing Tom1 resulted in an increase of symptom development. By
      contrast, tomato plants infected with the knockout mutants showed a delay in the
      disease process, indicating that Tom1, although not essential for pathogenicity,
      is required for the full virulence of F. oxysporum. Total tomatinase activity in
      the disrupted strains was reduced only 25%, leading to beta(2)-tomatine as the
      main hydrolysis product of the saponin in vitro. In silico analysis of the F.
      oxysporum genome revealed the existence of four additional putative tomatinase
      genes with identities to tomatinases from family 3 of glycosyl hydrolases. These
      might be responsible for the remaining tomatinase activity in the Deltatom1
      mutants. Our results indicate that detoxification of alpha-tomatine in F.
      oxysporum is carried out by several tomatinase activities, suggesting the
      importance of these enzymes during the infection process.

PMID- 18624638
TI  - Soil bacteria confer plant salt tolerance by tissue-specific regulation of the
      sodium transporter HKT1.
AB  - Elevated sodium (Na(+)) decreases plant growth and, thereby, agricultural
      productivity. The ion transporter high-affinity K(+) transporter (HKT)1 controls
      Na(+) import in roots, yet dysfunction or overexpression of HKT1 fails to
      increase salt tolerance, raising questions as to HKT1's role in regulating Na(+)
      homeostasis. Here, we report that tissue-specific regulation of HKT1 by the soil
      bacterium Bacillus subtilis GB03 confers salt tolerance in Arabidopsis thaliana.
      Under salt stress (100 mM NaCl), GB03 concurrently down- and upregulates HKT1
      expression in roots and shoots, respectively, resulting in lower Na(+)
      accumulation throughout the plant compared with controls. Consistent with HKT1
      participation in GB03-induced salt tolerance, GB03 fails to rescue salt-stressed
      athkt1 mutants from stunted foliar growth and elevated total Na(+) whereas salt
      stressed Na(+) export mutants sos3 show GB03-induced salt tolerance with enhanced
      shoot and root growth as well as reduced total Na(+). These results demonstrate
      that tissue-specific regulation of HKT1 is critical for managing Na(+)
      homeostasis in salt-stressed plants, as well as underscore the breadth and
      sophistication of plant-microbe interactions.

PMID- 18624639
TI  - Basic compatibility of Albugo candida in Arabidopsis thaliana and Brassica juncea
      causes broad-spectrum suppression of innate immunity.
AB  - A biotrophic parasite often depends on an intrinsic ability to suppress host
      defenses in a manner that will enable it to infect and successfully colonize a
      susceptible host. If the suppressed defenses otherwise would have been effective
      against alternative pathogens, it follows that primary infection by the
      "suppressive" biotroph potentially could enhance susceptibility of the host to
      secondary infection by avirulent pathogens. This phenomenon previously has been
      attributed to true fungi such as rust (basidiomycete) and powdery mildew
      (ascomycete) pathogens. In our study, we observed broad-spectrum suppression of
      host defense by the oomycete Albugo candida (white blister rust) in the wild
      crucifer Arabidopsis thaliana and a domesticated relative, Brassica juncea. A.
      candida subsp. arabidopsis suppressed the "runaway cell death" phenotype of the
      lesion mimic mutant lsd1 in Arabidopsis thaliana in a sustained manner even after
      subsequent inoculation with avirulent Hyaloperonospora arabidopsis (Arabidopsis
      thaliana downy mildew). In sequential inoculation experiments, we show that
      preinfection by virulent Albugo candida can suppress disease resistance in
      cotyledons to several downy mildew pathogens, including contrasting examples of
      genotype resistance to H. arabidopsis in Arabidopsis thaliana that differ in the
      R protein and modes of defense signaling used to confer the resistance; genotype
      specific resistance in B. juncea to H. parasitica (Brassica downy mildew;
      isolates derived from B. juncea); species level (nonhost) resistance in both
      crucifers to Bremia lactucae (lettuce downy mildew) and an isolate of the H.
      parasitica race derived from Brassica oleracea; and nonhost resistance in B.
      juncea to H. arabidopsis. Broad-spectrum powdery mildew resistance conferred by
      RPW8 also was suppressed in Arabidopsis thaliana to two morphotypes of Erysiphe
      spp. following pre-infection with A. candida subsp. arabidopsis.

PMID- 18624640
TI  - WRR4 encodes a TIR-NB-LRR protein that confers broad-spectrum white rust
      resistance in Arabidopsis thaliana to four physiological races of Albugo candida.
AB  - White blister rust in the Brassicaceae is emerging as a superb model for
      exploring how plant biodiversity has channeled speciation of biotrophic
      parasites. The causal agents of white rust across a wide breadth of cruciferous
      hosts currently are named as variants of a single oomycete species, Albugo
      candida. The most notable examples include a major group of physiological races
      that each are economically destructive in a different vegetable or oilseed crop
      of Brassica juncea (A. candida race 2), B. rapa (race 7), or B. oleracea (race
      9); or parasitic on wild crucifers such as Capsella bursa-pastoris (race 4).
      Arabidopsis thaliana is innately immune to these races of A. candida under
      natural conditions; however, it commonly hosts its own molecularly distinct
      subspecies of A. candida (A. candida subsp. arabidopsis). In the laboratory, we
      have identified several accessions of Arabidopsis thaliana (e.g.,. Ws-3) that can
      permit varying degrees of rust development following inoculation with A. candida
      races 2, 4, and 7, whereas race 9 is universally incompatible in Arabidopsis
      thaliana and nonrusting resistance is the most prevalent outcome of interactions
      with the other races. Subtle variation in resistance phenotypes is evident,
      observed initially with an isolate of A. candida race 4, indicating additional
      genetic variation. Therefore, we used the race 4 isolate for map-based cloning of
      the first of many expected white rust resistance (WRR) genes. This gene was
      designated WRR4 and encodes a cytoplasmic toll-interleukin receptor-like
      nucleotide-binding leucine-rich repeat receptor-like protein that confers a
      dominant, broad-spectrum white rust resistance in the Arabidopsis thaliana
      accession Columbia to representative isolates of A. candida races 2, 4, 7, and 9,
      as verified by transgenic expression of the Columbia allele in Ws-3. The WRR4
      protein requires functional expression of the lipase-like protein EDS1 but not
      the paralogous protein PAD4, and confers full immunity that masks an underlying
      nonhypersensitive incompatibility in Columbia to A. candida race 4. This residual
      incompatibility is independent of functional EDS1.

PMID- 18624641
TI  - Expression of Medicago truncatula genes responsive to nitric oxide in pathogenic
      and symbiotic conditions.
AB  - Nitric oxide (NO) is involved in diverse physiological processes in plants,
      including growth, development, response to pathogens, and interactions with
      beneficial microorganisms. In this work, a dedicated microarray representing the
      widest database available of NO-related transcripts in plants has been produced
      with 999 genes identified by a cDNA amplified fragment length polymorphism
      analysis as modulated in Medicago truncatula roots treated with two NO donors.
      The microarray then was used to monitor the expression of NO-responsive genes in
      M. truncatula during the incompatible interaction with the foliar pathogen
      Colletotrichum trifolii race 1 and during the symbiotic interaction with
      Sinorhizobium meliloti 1,021. A wide modulation of NO-related genes has been
      detected during the hypersensitive reaction or during nodule formation and is
      discussed with special emphasis on the physiological relevance of these genes in
      the context of the two biotic interactions. This work clearly shows that NO
      responsive genes behave differently depending on the plant organ and on the type
      of interaction, strengthening the need to consider regulatory networks, including
      different signaling molecules.

PMID- 18624642
TI  - Expression of two functionally distinct plant endo-beta-1,4-glucanases is
      essential for the compatible interaction between potato cyst nematode and its
      hosts.
AB  - For the proliferation of their feeding sites (syncytia), the potato cyst nematode
      Globodera rostochiensis is thought to recruit plant endo-beta-1,4-glucanases
      (EGases, EC. 3.2.1.4). Reverse-transcription polymerase chain reaction
      experiments on tomato (Solanum lycopersicum) indicated that the expression of two
      out of the at least eight EGases, namely Sl-cel7 and Sl-cel9C1, is specifically
      upregulated during syncytium formation. In situ hybridization and immunodetection
      studies demonstrated that both EGases are specifically expressed inside and
      adjacent to proliferating syncytia. To assess the importance of Sl-cel7 and Sl
      cel9C1 for nematode development, we decided to knock them out individually. Sl
      cel9C1 probably is the only class C EGase in tomato, and we were unable to
      regenerate Sl-cel9C1-silenced plants. Potato (S. tuberosum), a close relative of
      tomato, harbors at least two class C EGases, and St-cel7-or St-cel9C1-silenced
      potato plants showed no obvious aberrant phenotype. Infection with potato cyst
      nematodes resulted in a severe reduction of the number of adult females (up to
      60%) and a sharp increase in the fraction of females without eggs (up to 89%).
      Hence, the recruitment of CEL7, an enzyme that uses xyloglucan and noncrystalline
      cellulose as natural substrates, and CEL9C1, an enzyme that uses crystalline
      cellulose, is essential for growth and development of potato cyst nematodes.

PMID- 18624643
TI  - The root-colonizing endophyte Pirifomospora indica confers drought tolerance in
      Arabidopsis by stimulating the expression of drought stress-related genes in
      leaves.
AB  - Piriformospora indica is an endophytic fungus that colonizes the roots of many
      plant species, including Arabidopsis. We exposed 18-day-old Arabidopsis
      seedlings, which were either cocultivated with the fungus or mock-treated for the
      last 9 days, to mild drought stress for 84 h. During the first 36 to 48 h,
      seedlings cocultivated with the fungus continued to grow, while the uncolonized
      controls did not. This results in a threefold difference in the fresh weight and
      a more than twofold difference in the chlorophyll content. The photosynthetic
      efficiency was only slightly reduced in the colonized (F variable/F maximum
      [Fv/Fm] at t(0 h) = 0.82 and t(36 h) = 0.79) and was severely impaired in the
      uncolonized (Fv/Fm at t(0 h) = 0.81 and (t)(36 h) = 0.49) seedlings, which also
      showed symptoms of withering. When seedlings exposed to drought stress for 72 or
      84 h were transferred to soil, 10% (72 h) and none (84 h) of uncolonized
      seedlings reached the flowering stage and produced seeds, while 59% (72 h) and
      47% (84 h) of the colonized seedlings flowered and produced seeds. After exposure
      to drought stress for 3 h, the message levels for RESPONSE TO DEHYDRATION 29A,
      EARLY RESPONSE TO DEHYDRATION1, ANAC072, DEHYDRATION-RESPONSE ELEMENT BINDING
      PROTEIN2A, SALT-, AND DROUGHT-INDUCED RING FINGER1, phospholipase Ddelta,
      CALCINEURIN B-LIKE PROTEIN (CBL)1, CBL-INTERACTING PROTEIN KINASE3, and the
      histone acetyltransferase (HAT) were upregulated in the leaves of P. indica
      colonized seedlings. Uncolonized seedlings responded 3 to 6 h later, and the
      message levels increased much less. We identified an Arabidopsis ethylmethane
      sulfonate mutant that is less resistant to drought stress and in which the stress
      related genes were not upregulated in the presence of P. indica. Thus, P. indica
      confers drought-stress tolerance to Arabidopsis, and this is associated with the
      priming of the expression of a quite diverse set of stress-related genes in the
      leaves. Transfer to soil was again associated with a faster and stronger
      upregulation of the message levels for phospholipase Ddelta, CBL1, and HAT in P.
      indica-colonized seedlings, indicating that this response might also contribute
      to better survival on soil.

PMID- 18624644
TI  - NADPH oxidases are involved in differentiation and pathogenicity in Botrytis
      cinerea.
AB  - Nicotinamide adenine dinucleotide (NADPH) oxidases have been shown to be involved
      in various differentiation processes in fungi. We investigated the role of two
      NADPH oxidases in the necrotrophic phytopathogenic fungus, Botrytis cinerea. The
      genes bcnoxA and bcnoxB were cloned and characterized; their deduced amino acid
      sequences show high homology to fungal NADPH oxidases. Analyses of single and
      double knock-out mutants of both NADPH oxidase genes showed that both bcnoxA and
      bcnoxB are involved in formation of sclerotia. Both genes have a great impact on
      pathogenicity: whereas bcnoxB mutants showed a retarded formation of primary
      lesions, probably due to an impaired formation of penetration structures, bcnoxA
      mutants were able to penetrate host tissue in the same way as the wild type but
      were much slower in colonizing the host tissue. Double mutants showed an additive
      effect: they were aberrant in penetration and colonization of plant tissue and,
      therefore, almost nonpathogenic. To study the structure of the fungal Nox complex
      in more detail, bcnoxR (encoding a homolog of the mammalian p67(phox), a
      regulatory subunit of the Nox complex) was functionally characterized. The
      phenotype of DeltabcnoxR mutants is identical to that of DeltabcnoxAB double
      mutants, providing evidence that BcnoxR is involved in activation of both Bcnox
      enzymes.

PMID- 18624645
TI  - Structure of the glucanase inhibitor protein (GIP) family from phytophthora
      species suggests coevolution with plant endo-beta-1,3-glucanases.
AB  - During invasion of their plant hosts, species of the oomycete genus Phytophthora
      secrete glucanase inhibitor proteins (GIPs) into the plant apoplast, which bind
      and inhibit the activity of plant extracellular endo-beta-1,3-glucanases
      (EGases). GIPs show structural homology to the chymotrypsin class of serine
      proteases (SP) but lack proteolytic activity due to the absence of an intact
      catalytic triad and, thus, belong to a broader class of proteins called serine
      protease homologs (SPH). To study the evolutionary relationship between GIPs and
      functional SP, database searches were used to identify 48 GIP homologs in the P.
      sojae, P. ramorum, and P. infestans genomes, composing GIPs, SPH, and potentially
      functional SP. Analyses of P. infestans-inoculated tomato leaves showed that P.
      infestans GIPs and tomato EGases are present in the apoplast and form stable
      complexes in planta. Studies of the temporal expression of a four-membered GIP
      family from P. infestans (PiGIP1 to PiGIP4) further revealed that the genes show
      distinctly different patterns during an infection timecourse. Codon evolution
      analyses of GIP homologs identified several positively selected peptide sites and
      structural modeling revealed them to be in close proximity to rapidly evolving
      EGase residues, suggesting that the interaction between GIPs and EGases has the
      hallmarks of a coevolving molecular arms race.

PMID- 18624646
TI  - Duplication of plasmid-borne nitrite reductase gene nirK in the wheat-associated
      plant growth-promoting rhizobacterium Azospirillum brasilense Sp245.
AB  - In the plant growth-promoting rhizobacterium Azospirillum brasilense Sp245,
      nitric oxide produced by denitrification could be a signal involved in
      stimulation of root branching, and the dissimilatory nitrite reductase gene nirK
      is upregulated on wheat roots. Here, it was found that Sp245 did not contain one
      copy of nirK but two (named nirK1 and nirK2), localized on two different
      plasmids, including one plasmid prone to rearrangements. Their deduced protein
      sequences displayed 99.2% identity but their promoter regions and upstream
      genetic environment differed. Phylogenetic studies revealed that nirK1 and nirK2
      clustered next to most beta-proteobacterial sequences rather than in the vicinity
      of other Azospirillum spp. and most alpha-proteobacterial sequences, regardless
      of whether DNA or deduced protein sequences were used. This points to past
      horizontal gene transfers. Analysis of the number of nonsynonymous and synonymous
      substitutions per site indicated that nirK has been subjected to neutral
      selection in bacteria. The use of transcriptional fusions with egfp, encoding an
      enhanced green fluorescent protein variant, revealed that both nirK1 and nirK2
      promoter regions were upregulated in vitro under microaerobiosis or the presence
      of nitrite as well as on wheat roots. The analysis of nirK1 and nirK2 mutants
      revealed that the two genes were functional. Overall, results suggest that nirK
      has been acquired horizontally by A. brasilense Sp245 from a distant relative and
      underwent subsequent duplication; however, both paralogs remained functional and
      retained their upregulation by the plant partner.

PMID- 18624647
TI  - Molecular analysis of lipoxygenases associated with nodule development in
      soybean.
AB  - We utilized transcriptional profiling to identify genes associated with nodule
      development in soybean. Many of the candidate genes were predicted to be involved
      in processes such as defense, metabolism, transcriptional regulation, oxidation,
      or iron storage. Here, we describe the detailed characterization of one specific
      class of genes that encode the enzyme lipoxygenase (LOX). The LOX9 and LOX10
      genes identified by microarray analysis represent novel soybean LOXs expressed in
      developing nodules. LOX expression during nodulation was relatively complex, with
      at least eight different LOX genes expressed in soybean nodules. Histochemical
      analyses utilizing LOX9 promoter::beta-glucuronidase (GUS) fusion constructs in
      transgenic soybean hairy roots suggest that this gene is involved in the growth
      and development of specific cells within the root and nodules. In soybean roots,
      LOX9 was expressed specifically in the developing phloem. In nodules, the
      expression of LOX9 was correlated with the development of cells in the
      vasculature and lenticels. The use of RNAi in transgenic hairy roots reduced LOX
      expression by approximately 95%. Despite this significant reduction in LOX
      expression, there was no detectable effect on the development of roots or
      nodules. Our findings are discussed with respect to the potential function of
      LOXs in nodulation.

PMID- 18624648
TI  - Outbreaks of influenza A among nonvaccinated healthcare workers: implications for
      resource-limited settings.
AB  - We identified 3 outbreaks of influenza A (attack rates, 18%-24%) among Thai
      healthcare workers in intensive care units. All outbreaks were epidemiologically
      linked to an index patient with pneumonia due to influenza A virus (subtype
      H3N2). The investigations of these outbreaks incurred costs that exceeded the
      estimated costs of healthcare worker influenza vaccination by more than 10-fold.

PMID- 18624649
TI  - Risk factors for surgical site infection in kidney transplant recipients.
AB  - We analyzed the epidemiologic characteristics and risk factors for surgical site
      infection (SSI) in kidney transplant recipients. From among 1,939 kidney
      transplant recipients, 120 with corresponding control subjects were evaluated in
      this study (1:1 ratio). Reoperation, chronic glomerulonephritis, acute graft
      rejection, delayed graft function, diabetes, and high body mass index were
      identified in the analysis as risk factors for SSI.

PMID- 18624650
TI  - Variation in mortality rates among long-term care facilities for residents with
      lower respiratory tract infection.
AB  - OBJECTIVE: To identify variables contributing to interfacility differences in
      mortality among residents of long-term care facilities who have lower respiratory
      tract infection. DESIGN: Multicenter, prospective, 1-year observational study.
      SETTING: Twenty-one long-term care facilities in 4 geographic areas of Canada.
      PARTICIPANTS: Residents of long-term care facilities prescribed antimicrobials
      for treatment of lower respiratory tract infection. METHODS: Mortality rates were
      calculated for 3 definitions of lower respiratory tract infection: episodes with
      a clinical or radiographic diagnosis and treated with antimicrobials (definition
      1); episodes with a physician diagnosis of pneumonia (definition 2); and episodes
      with chest radiography findings consistent with pneumonia (definition 3).
      Multilevel modeling was used to evaluate variables describing premorbid resident
      status, clinical presentation, management, and facility characteristics.
      Multivariable models were developed to identify independent predictors of
      mortality and determine whether facility-level variables remained independently
      associated with mortality rate after incorporation of individual-level variables.
      RESULTS: Facility mortality rates varied from 0% to 17.8% for definition 1, from
      0% to 47.1% for definition 2, and from 0% to 37.5% for definition 3. There were
      significant differences in mortality rate depending on which definition was used;
      for definitions 1 and 2, there were significant differences in mortality rate
      across facilities. Poorer premorbid resident status and a more severe
      presentation remained independent predictors of mortality in the multivariable
      analysis. There were also significantly increased mortality rates for episodes in
      which a fluoroquinolone was prescribed for initial treatment. For definitions 1
      and 3, facility-level variables remained independently associated with mortality
      rate in the final multivariable model. CONCLUSIONS: Rates of mortality due to
      lower respiratory tract infection varied among long-term care facilities and
      differed within a facility, depending on the definition applied. Variables
      describing premorbid resident status, severity of presentation, and management
      did not fully explain the variation in mortality rate. Some facility-level
      variables remained independent predictors of mortality.

PMID- 18624653
TI  - Optimization of decision making in multilayer networks: the role of locus
      coeruleus.
AB  - Previous theoretical work has shown that a single-layer neural network can
      implement the optimal decision process for simple, two-alternative forced-choice
      (2AFC) tasks. However, it is likely that the mammalian brain comprises multilayer
      networks, raising the question of whether and how optimal performance can be
      approximated in such an architecture. Here, we present theoretical work
      suggesting that the noradrenergic nucleus locus coeruleus (LC) may help optimize
      2AFC decision making in the brain. This is based on the observations that neurons
      of the LC selectively fire following the presentation of salient stimuli in
      decision tasks and that the corresponding release of norepinephrine can
      transiently increase the responsivity, or gain, of cortical processing units. We
      describe computational simulations that investigate the role of such gain changes
      in optimizing performance of 2AFC decision making. In the tasks we model, no
      prior cueing or knowledge of stimulus onset time is assumed. Performance is
      assessed in terms of the rate of correct responses over time (the reward rate).
      We first present the results of a single-layer model that accumulates
      (integrates) sensory input and implements the decision process as a threshold
      crossing. Gain transients, representing the modulatory effect of the LC, are
      driven by separate threshold crossings in this layer. We optimize over all free
      parameters to determine the maximum reward rate achievable by this model and
      compare it to the maximum reward rate when gain is held fixed. We find that the
      dynamic gain mechanism yields no improvement in reward for this single-layer
      model. We then examine a two-layer model, in which competing sensory accumulators
      in the first layer (capable of implementing the task relevant decision) pass
      activity to response accumulators in a second layer. Again, we compare a version
      in which threshold crossing in the first (decision) layer elicits an LC response
      (and a concomitant increase in gain) with a fixed-gain version of the model.
      Here, we find that gain transients modeling the LC phasic response yield an
      improvement in reward rate of 12% to 24%. Furthermore, we show that the timing
      characteristics of these gain transients agree with observations concerning LC
      firing patterns reported in recent experimental studies. This provides converging
      evidence for the hypothesis that the LC optimizes processes underlying 2AFC
      decision making in multilayer networks.

PMID- 18624651
TI  - Implementation of an industrial systems-engineering approach to reduce the
      incidence of methicillin-resistant Staphylococcus aureus infection.
AB  - OBJECTIVE: To measure the effectiveness of an industrial systems-engineering
      approach to a methicillin-resistant Staphylococcus aureus (MRSA) prevention
      program. DESIGN: Before-after intervention study. SETTING: An intensive care unit
      (ICU) and a surgical unit that was not an ICU in the Pittsburgh Veterans
      Administration hospital. PATIENTS: All patients admitted to the study units.
      INTERVENTION: We implemented an MRSA infection control program that consisted of
      the following 4 elements: (1) the use of standard precautions for all patient
      contact, with emphasis on hand hygiene; (2) the use of contact precautions for
      interactions with patients known to be infected or colonized with MRSA; (3) the
      use of active surveillance cultures to identify patients who were
      asymptomatically colonized with MRSA; and (4) use of an industrial systems
      engineering approach, the Toyota Production System, to facilitate consistent and
      reliable adherence to the infection control program. RESULTS: The rate of
      healthcare-associated MRSA infection in the surgical unit decreased from 1.56
      infections per 1,000 patient-days in the 2 years before the intervention to 0.63
      infections per 1,000 patient-days in the 4 years after the intervention (a 60%
      reduction; P = .003). The rate of healthcare-associated MRSA infection in the ICU
      decreased from 5.45 infections per 1,000 patient-days in the 2 years before to
      the intervention to 1.35 infections per 1,000 patient-days in the 3 years after
      the intervention (a 75% reduction; P = .001). The combined estimate for reduction
      in the incidence of infection after the intervention in the 2 units was 68% (95%
      confidence interval, 50%-79%; P < .001). CONCLUSIONS: Sustained reduction in the
      incidence of MRSA infection is possible in a setting where this pathogen is
      endemic. An industrial systems-engineering approach can be adapted to facilitate
      consistent and reliable adherence to MRSA infection prevention practices in
      healthcare facilities.

PMID- 18624654
TI  - A fast, streaming SIMD Extensions 2, logistic squashing function.
AB  - Schraudolph proposed an excellent exponential approximation providing increased
      performance particularly suited to the logistic squashing function used within
      many neural networking applications. This note applies Intel's streaming SIMD
      Extensions 2 (SSE2), where SIMD is single instruction multiple data, of the
      Pentium IV class processor to Schraudolph's technique, further increasing the
      performance of the logistic squashing function. It was found that the calculation
      of the new 32-bit SSE2 logistic squashing function described here was up to 38
      times faster than the conventional exponential function and up to 16 times faster
      than a Schraudolph-style 32-bit method on an Intel Pentium D 3.6 GHz CPU.

PMID- 18624656
TI  - A mathematical analysis of the effects of Hebbian learning rules on the dynamics
      and structure of discrete-time random recurrent neural networks.
AB  - We present a mathematical analysis of the effects of Hebbian learning in random
      recurrent neural networks, with a generic Hebbian learning rule, including
      passive forgetting and different timescales, for neuronal activity and learning
      dynamics. Previous numerical work has reported that Hebbian learning drives the
      system from chaos to a steady state through a sequence of bifurcations. Here, we
      interpret these results mathematically and show that these effects, involving a
      complex coupling between neuronal dynamics and synaptic graph structure, can be
      analyzed using Jacobian matrices, which introduce both a structural and a
      dynamical point of view on neural network evolution. Furthermore, we show that
      sensitivity to a learned pattern is maximal when the largest Lyapunov exponent is
      close to 0. We discuss how neural networks may take advantage of this regime of
      high functional interest.

PMID- 18624657
TI  - Stimulus representation and the timing of reward-prediction errors in models of
      the dopamine system.
AB  - The phasic firing of dopamine neurons has been theorized to encode a reward
      prediction error as formalized by the temporal-difference (TD) algorithm in
      reinforcement learning. Most TD models of dopamine have assumed a stimulus
      representation, known as the complete serial compound, in which each moment in a
      trial is distinctly represented. We introduce a more realistic temporal stimulus
      representation for the TD model. In our model, all external stimuli, including
      rewards, spawn a series of internal microstimuli, which grow weaker and more
      diffuse over time. These microstimuli are used by the TD learning algorithm to
      generate predictions of future reward. This new stimulus representation injects
      temporal generalization into the TD model and enhances correspondence between
      model and data in several experiments, including those when rewards are omitted
      or received early. This improved fit mostly derives from the absence of large
      negative errors in the new model, suggesting that dopamine alone can encode the
      full range of TD errors in these situations.

PMID- 18624658
TI  - Sleeping our way to weight normalization and stable learning.
AB  - The functions of sleep have been an enduring mystery. Tononi and Cirelli (2003)
      hypothesized that one of the functions of slow-wave sleep is to scale down
      synapses in the cortex that have strengthened during awake learning. We create a
      computational model to test the functionality of this idea and examine some of
      its implications. We show that synaptic scaling during slow-wave sleep is capable
      of keeping Hebbian learning in check and that it enables stable development. We
      also show theoretically how it implements classical weight normalization, which
      has been in common use in neural models for decades. Finally, a significant
      computational limitation of this form of synaptic scaling is revealed through
      computer simulations.

PMID- 18624660
TI  - Optimal approximation of signal priors.
AB  - In signal restoration by Bayesian inference, one typically uses a parametric
      model of the prior distribution of the signal. Here, we consider how the
      parameters of a prior model should be estimated from observations of uncorrupted
      signals. A lot of recent work has implicitly assumed that maximum likelihood
      estimation is the optimal estimation method. Our results imply that this is not
      the case. We first obtain an objective function that approximates the error
      occurred in signal restoration due to an imperfect prior model. Next, we show
      that in an important special case (small gaussian noise), the error is the same
      as the score-matching objective function, which was previously proposed as an
      alternative for likelihood based on purely computational considerations. Our
      analysis thus shows that score matching combines computational simplicity with
      statistical optimality in signal restoration, providing a viable alternative to
      maximum likelihood methods. We also show how the method leads to a new intuitive
      and geometric interpretation of structure inherent in probability distributions.

PMID- 18624663
TI  - Analytical and simulation results for the stochastic spatial Fitzhugh-Nagumo
      model neuron.
AB  - For the Fitzhugh-Nagumo system with space-time white noise, we use numerical
      methods to consider the generation of action potentials and the reliability of
      transmission in the presence of noise. The accuracy of simulated solutions is
      verified by comparison with known exact analytical results. Noise of small
      amplitude may prevent transmission directly, whereas larger-amplitude noise may
      also interfere by producing secondary nonlocal responses. The probability of
      transmission as a function of noise amplitude is found for both uniform noise and
      noise restricted to a patch. For certain parameter ranges, the recovery variable
      may be neglected to give a single-component nonlinear diffusion with space-time
      white noise. In this case, analytical results are obtained for small
      perturbations and noise, which agree well with simulation results. For the
      voltage variable, expressions are given for the mean, covariance, and variance
      and their steady-state forms. The spectral density of the voltage is also
      obtained. Numerical examples are given of the difference between the properties
      of nonlinear and linear cables, and the validity of the expressions obtained for
      the statistical properties is investigated as a function of noise amplitude. For
      given parameters, analytical results are in good agreement with simulation until
      a certain critical noise amplitude is reached, which can be estimated. The role
      of trigger zones in increasing the reliability of transmission is discussed.

PMID- 18624664
TI  - Interspecific associations between circulating antioxidant levels and life
      history variation in birds.
AB  - Antioxidants play an important role in protecting tissues against aging
      associated oxidative damage and are thus prime candidates for relating
      physiological mechanisms to variation in life histories. We measured total
      antioxidant capacity, antioxidant response to stress, and levels of uric acid,
      vitamin E, and four carotenoids in 95 avian species, mostly passerines from
      Michigan or Panama. We compared antioxidant measures to seven variables related
      to life histories (clutch size, survival rate, incubation period, nestling
      period, basal metabolic rate, body mass, and whether the species lived in a
      tropical or temperate climate). Life-history-related traits varied over at least
      three statistically independent axes. Higher antioxidant levels were generally
      characteristic of more rapid development, lower survival rate, smaller body size,
      larger clutch size, and higher mass-adjusted metabolic rate, but the
      relationships of particular antioxidants with individual life-history traits
      showed considerable complexity. Antioxidant-life history associations differed
      between tropical and temperate species and varied with respect to taxonomic
      sampling. Vitamin E showed few relationships with life-history traits. Overall,
      our results partly support the hypothesis that antioxidant levels evolve to
      mirror free radical production. Clearly, however, the complex patterns of
      physiological diversification observed here result from the interplay of many
      factors, likely including not just investment in somatic maintenance but also
      phylogenetic constraint, diet, and other aspects of ecology.

PMID- 18624665
TI  - Contamination, acquisition, and transmission of pathogens: implications for
      research and practice of infection control.

PMID- 18624666
TI  - Impact of an environmental cleaning intervention on the presence of methicillin
      resistant Staphylococcus aureus and vancomycin-resistant enterococci on surfaces
      in intensive care unit rooms.
AB  - OBJECTIVES: To evaluate the adequacy of discharge room cleaning and the impact of
      a cleaning intervention on the presence of methicillin-resistant Staphylococcus
      aureus (MRSA) and vancomycin-resistant enterococci (VRE) on environmental
      surfaces in intensive care unit (ICU) rooms. DESIGN: Prospective environmental
      study. SETTING AND SAMPLE: Convenience sample of ICU rooms in an academic
      hospital. METHODS AND INTERVENTION: The intervention consisted of (1) a change
      from the use of pour bottles to bucket immersion for applying disinfectant to
      cleaning cloths, (2) an educational campaign, and (3) feedback regarding adequacy
      of discharge cleaning. Cleaning of 15 surfaces was evaluated by inspecting for
      removal of a preapplied mark, visible only with an ultraviolet lamp ("black
      light"). Six surfaces were cultured for MRSA or VRE contamination. Outcomes of
      mark removal and culture positivity were evaluated by chi(2) testing and
      generalized linear mixed models, clustering by room. RESULTS: The black-light
      mark was removed from 44% of surfaces at baseline, compared with 71% during the
      intervention (P < .001). The intervention increased the likelihood of removal of
      black-light marks after discharge cleaning (odds ratio, 4.4; P < .001),
      controlling for ICU type (medical vs surgical) and type of surface. The
      intervention reduced the likelihood of an environmental culture positive for MRSA
      or VRE (proportion of cultures positive, 45% at baseline vs 27% during the
      intervention; adjusted odds ratio, 0.4; P = .02). Broad, flat surfaces were more
      likely to be cleaned than were doorknobs and sink or toilet handles. CONCLUSIONS:
      Increasing the volume of disinfectant applied to environmental surfaces,
      providing education for Environmental Services staff, and instituting feedback
      with a black-light marker improved cleaning and reduced the frequency of MRSA and
      VRE contamination.

PMID- 18624667
TI  - Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) acquisition
      in roommate contacts of patients colonized or infected with MRSA in an acute-care
      hospital.
AB  - OBJECTIVE: To identify risk factors for acquisition of methicillin-resistant
      Staphylococcus aureus (MRSA) in patients exposed to an MRSA-colonized roommate.
      DESIGN: Retrospective cohort study. SETTING: A 472-bed acute-care teaching
      hospital in Toronto, Canada. PATIENTS: Inpatients who shared a room between 1996
      and 2004 with a patient who had unrecognized MRSA colonization. METHODS: Exposed
      roommates were identified from infection-control logs and from results of
      screening for MRSA in the microbiology database. Completed follow-up was defined
      as completion of at least 2 sets of screening cultures (swab samples from the
      nares, the rectum, and skin lesions), with at least 1 set of samples obtained 7
      10 days after the last exposure. Chart reviews were performed to compare those
      who did and did not become colonized with MRSA. RESULTS: Of 326 roommates, 198
      (61.7%) had completed follow-up, and 25 (12.6%) acquired MRSA by day 7-10 after
      exposure was recognized, all with strains indistinguishable by pulsed-field gel
      electrophoresis from those of their roommate. Two (2%) of 101 patients were not
      colonized at day 7-10 but, with subsequent testing, were identified as being
      colonized with the same strain as their roommate (one at day 16 and one at day 18
      after exposure). A history of alcohol abuse (odds ratio [OR], 9.8 [95% confidence
      limits {CLs}, 1.8, 53]), exposure to a patient with nosocomially acquired MRSA
      (OR, 20 [95% CLs, 2.4, 171]), increasing care dependency (OR per activity of
      daily living, 1.7 [95% CLs, 1.1, 2.7]), and having received levofloxacin (OR, 3.6
      [95% CLs, 1.1, 12]) were associated with MRSA acquisition. CONCLUSIONS: Roommates
      of patients with MRSA are at significant risk for becoming colonized. Further
      study is needed of the impact of hospital antimicrobial formulary decisions on
      the risk of acquisition of MRSA.

PMID- 18624668
TI  - Differential correlation between rates of antimicrobial drug consumption and
      prevalence of antimicrobial resistance in a tertiary care hospital in Greece.
AB  - OBJECTIVE: To investigate whether there is a correlation between the rates of
      antimicrobial drug consumption in hospital departments and the prevalence of
      antimicrobial resistance among clinically important bacteria recovered in the
      hospital. DESIGN: Retrospective study. SETTING: Tertiary care hospital in Greece.
      METHODS: Data on antimicrobial consumption (from January 2001 through December
      2004) were expressed as defined daily doses per 100 bed-days. The prevalence of
      antimicrobial resistance among isolates of Escherichia coli, Klebsiella
      pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus
      faecium recovered during the same time period were calculated by the microbiology
      department. We then performed the following analyses: (1) a comparison of the
      consumption rates for different antimicrobial groups in individual hospital
      departments, (2) a comparison of the prevalence of resistance to different
      antimicrobials, and (3) a correlation analysis of antimicrobial consumption rates
      and the prevalence of antimicrobial resistance. RESULTS: The rates of
      antimicrobial consumption and the prevalence of resistance varied substantially
      among the hospital's departments. The annual rate of consumption for carbapenems
      correlated with the rate of consumption for glycopeptides and third-generation
      cephalosporins (P < .05). Among P. aeruginosa isolates, the prevalence of
      imipenem resistance correlated with the prevalence of resistance to amikacin,
      ciprofloxacin, and ceftazidime (P < .05). The rate of carbapenem consumption
      correlated with the prevalence of imipenem resistance among P. aeruginosa and A.
      baumannii isolates (P < .05). The rate of aminoglycoside consumption correlated
      with the prevalence of amikacin resistance among P. aeruginosa, K. pneumoniae,
      and E. coli isolates (P < .05). However, the rate of consumption for
      fluoroquinolones and glycopeptides had no correlation with the prevalence of
      ciprofloxacin resistance among gram-negative bacteria or vancomycin resistance
      among E. faecium isolates. CONCLUSIONS: These data are suggestive of a
      differential relationship between antimicrobial consumption and the prevalence of
      antimicrobial resistance among various species and for various antimicrobial
      agents. These findings may help to optimize antimicrobial prescription policies
      in the hospital, especially in departments that have both high rates of
      antimicrobial consumption and a high prevalence of antimicrobial resistance.

PMID- 18624669
TI  - Predictors of mortality from community-onset bloodstream infections due to
      extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella
      pneumoniae.
AB  - In a cohort study of 36 patients with community-onset extended-spectrum beta
      lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae bloodstream
      infections, we found that predictors of mortality were community-onset infection
      with ESBL-producing K. pneumoniae pathogens (P = .02) and failure to receive an
      initial empirical regimen that included either beta-lactam and beta-lactamase
      inhibitors or a carbapenem (P = .04).

PMID- 18624670
TI  - Role of combination antibiogram in empirical treatment of infection due to
      multidrug-resistant Acinetobacter baumannii.

PMID- 18624671
TI  - Relationship between pathogenic and colonizing microorganisms detected in
      intensive care unit patients and in their family members and visitors.

PMID- 18624672
TI  - Whole-blood interferon-gamma release assay for baseline tuberculosis screening of
      healthcare workers at a Swiss university hospital.

PMID- 18624673
TI  - Overexpression of CXC chemokine receptors is required for the superior glioma
      tracking property of umbilical cord blood-derived mesenchymal stem cells.
AB  - Our observations indicate that umbilical cord blood-derived mesenchymal stem
      cells (UCB-MSCs) have a strong migration capacity toward the human glioma cell
      line, U-87 MG, LN18, U138, and U251, when compared to several other cancer cell
      lines. In order to identify soluble factors that function to attract UCB-MSCs, we
      used cytokine antibody arrays to screen changed cytokines in conditioned media
      from U-87 MG cells. Among these, interleukin-8 (IL-8) and growth-related oncogene
      (GRO-alpha) enhanced UCB-MSC migration. Furthermore, antibodies treatment against
      the IL-8 receptors reduced these migration events and overexpression of IL-8 in
      cells with lower level of IL-8 such as A549 could induce UCB-MSC migration. Since
      we found that the capacity of UCB-MSC migration is much higher than that of bone
      marrow-derived MSCs (BM-MSCs) toward either U-87 MG cells or recombinant IL-8, we
      compared the levels of the IL-8 receptor, CXC chemokine receptor 1 (CXCR1) and
      CXCR2 between two kinds of MSCs by RT-PCR and immunostaining. Expression levels
      of two receptors were much higher in UCB-MSCs than in BM-MSCs. These data suggest
      that higher levels of two IL-8 receptors could influence downstream signaling
      events affecting superior UCB-MSC migration toward the glioma cells.

PMID- 18624674
TI  - An update on metabolism studies using human hepatocytes in primary culture.
AB  - BACKGROUND: Cultured human hepatocytes are the closest in vitro model to human
      liver and constitute a very predictive model for drug metabolism in vivo. The
      variability observed in human hepatocytes reflects the existing phenotypic
      heterogeneity of cytochrome P450 expression in human liver. OBJECTIVES: As drug
      metabolism is the major source of pharmacokinetic variability in human beings,
      the main areas of current drug metabolism research in human hepatocytes are
      reviewed. METHODS: To speed up the selection of drug candidates, the evaluation
      of metabolic stability, metabolite profiling and identification, and drug-drug
      interaction potential are key issues in drug development. RESULTS/CONCLUSION: In
      vitro drug metabolism studies, which are inexpensive and readily carried out,
      serve as an adequate screening mechanism to characterize drug metabolites,
      elucidate their pathways, and make suggestions for further in vivo testing.

PMID- 18624675
TI  - Primary hepatocytes as a model to analyze species-specific toxicity and drug
      metabolism.
AB  - BACKGROUND: Compound failures have been emerging in later stages of
      pharmaceutical drug development and are in many cases not detected until the
      administration to humans in clinical trials or even after approval. Among the
      most frequent adverse effects are drug-induced liver injury generated by species
      specific susceptibilities (e.g., in xenobiotic metabolism and/or the occurrence
      of idiosyncratic drug hepatotoxicity). OBJECTIVES: Detecting or predicting
      unfavorable drug effects on the liver as early as possible in drug development is
      crucial in making the drug development process more efficient and the application
      of new drugs to humans in clinical studies and medical use safer. METHODS: To
      achieve this goal, primary hepatocyte cultures from various species, including
      humans, are analyzed for morphological, functional and gene expression
      alterations after compound treatment. RESULTS/CONCLUSION: Primary hepatocyte
      cultures appear to be a promising tool for the detection of general or liver
      toxicity and the evaluation of species-specific drug effects.

PMID- 18624676
TI  - Species selection considerations for preclinical toxicology studies for
      biotherapeutics.
AB  - BACKGROUND: Preclinical efficacy and safety studies, especially chronic studies,
      can be difficult to perform when the candidate therapeutic agent is a human
      protein due to the specificity of these molecules for the human target. The main
      issues are: i) the human protein or target may not be pharmacologically active in
      rodents or dogs, the standard toxicology species; or ii) the therapeutic agent
      may be so immunogenic in these species, that longer duration studies are not
      possible due to the formation of neutralizing antibodies. Thus, preclinical
      safety testing of biotherapeutics poses a particular challenge in selecting a
      relevant animal species for use in toxicology studies. OBJECTIVE: This article
      will discuss the considerations that are unique to safety assessment of
      biotherapeutics and will provide alternatives to the standard toxicity testing
      which is conducted for small molecules. METHODS: This article is based on
      published information with regards to species selection considerations as well as
      information from the FDA website on several marketed compounds. In addition,
      discussions of this topic that have occurred in public forums as well as the
      experience of the author are considered. CONCLUSION: The most important
      consideration in species selection for a biotherapeutic is that the drug is
      pharmacologically active in the preclinical species. This is a key consideration
      as biotherapeutics are highly targeted and rarely, if ever, demonstrate off
      target toxicity. Because of this species specificity, nonhuman primates are often
      the only relevant species that can be used to assess the safety of a
      biotherapeutic. Other alternatives such as use of a homologous protein in rodents
      or the use of transgenic or knockout mice can also be used to assess safety
      although the caveats to these approaches must be considered.

PMID- 18624677
TI  - Update on tools for evaluation of uridine diphosphoglucuronosyltransferase
      polymorphisms.
AB  - BACKGROUND: The uridine diphosphoglucuronosyltransferase (UGT) superfamily of
      enzymes catalyzes conjugative metabolism of numerous endobiotics and xenobiotics.
      Pharmacogenetic variation has been reported in almost all UGT family members.
      OBJECTIVE: To discuss tools available for evaluation of UGT polymorphisms.
      METHODS: Literature search was done to include all relevant UGT polymorphism
      studies involving in vitro methods. RESULTS/CONCLUSIONS: Studies evaluating
      associations between UGT genotype and resultant phenotype are described.
      Mammalian cells transfected with variant UGT isoforms or variant promoters have
      been developed. Human liver tissue genotyped for UGT genetic polymorphisms has
      been successfully used. New techniques to conduct these studies include RNA
      inhibition and development of transgenic animal models. Challenges and
      opportunities in the preclinical evaluation of UGT genotype-phenotype
      correlations are discussed.

PMID- 18624679
TI  - Potential role of intestinal first-pass metabolism in the prediction of drug-drug
      interactions.
AB  - BACKGROUND: The contribution of intestine to the magnitude of drug-drug
      interactions (DDI) may be significant, considering high levels of inhibitors in
      the gut lumen achieved during absorption and the abundance of metabolic enzymes
      in the mature enterocytes. Intestinal inhibition is incorporated in the DDI
      prediction models as the ratio of the intestinal wall availability in the
      presence and absence of the inhibitor (F(G)(') and F(G), respectively).
      OBJECTIVE: This review will focus on the ability of the current approaches to
      estimate the extent of intestinal DDI accurately, addressing predominantly the
      most abundant intestinal P450 enzyme, CYP3A4. METHODS: Considering the
      sensitivity of the DDI prediction models to the accuracy of the F(G) estimates,
      the current study focuses on 3 different in vitro and in vivo approaches to
      assess this parameter. RESULTS/CONCLUSION: The advantages and limitations of each
      of F(G) methods are outlined. Accurate assessment of this parameter is essential
      for the prediction of human drug clearance and drug-drug interaction potential.

PMID- 18624678
TI  - The pregnane X receptor: from bench to bedside.
AB  - BACKGROUND: The pregnane X receptor (PXR; NR1I2), a member of the nuclear
      receptor superfamily, regulates the expression of metabolic enzymes and
      transporters involved in the response of mammals to their chemical environment.
      OBJECTIVE: To summarize the functions and clinical implications of PXR. METHODS:
      In the current review, the clinical implications of PXR are discussed, and the
      use of genetically engineered PXR mouse models is highlighted.
      RESULTS/CONCLUSION: Recent advances in mouse models, including Pxr-null and PXR
      humanized mice, provide in vivo tools for evaluating the physiological functions
      of PXR and its role in controlling xenobiotic metabolism and transport. By using
      the PXR knockout and humanized mouse models, PXR was found to influence drug-drug
      interactions, hepatic steatosis, and the homeostasis of vitamin D, bile acids,
      and steroid hormones. PXR was also shown to influence inflammatory bowel
      diseases.

PMID- 18624680
TI  - Intestinal efflux transporters and drug absorption.
AB  - BACKGROUND: The intestinal epithelial membrane expresses ATP-binding cassette
      (ABC) transporters such as P-glycoprotein (P-gp), multi-drug resistance
      associated proteins (MRPs) and breast cancer resistance protein (BCRP), in
      addition to various solute carrier (SLC) transporters. These ABC transporters
      affect the oral bioavailability of their substrate drugs. OBJECTIVE: To review
      the contribution of ABC efflux transporters such as P-gp, MRP2, MRP3, and BCRP in
      the intestinal absorption of substrate drugs. METHODS: Discussion was made by
      focusing on the site-specific expression and function of these ABC transporters,
      and the solubility and permeability of their substrate compounds.
      RESULTS/CONCLUSION: The increase in the solubility and permeability of orally
      administered drugs could be the key to escape barrier function of ABC
      transporters, especially P-gp.

PMID- 18624681
TI  - Ibandronate in profile: drug characteristics and clinical efficacy.
AB  - BACKGROUND: Postmenopausal osteoporosis is a serious, chronic condition, for
      which nitrogen-containing bisphosphonates are now one of the treatments of
      choice. OBJECTIVE: To review the profile of ibandronate, a monthly oral (150 mg)
      or quarterly intravenous injection (3 mg) of bisphosphonate. METHODS: The
      literature search was limited to publications of ibandronate data.
      RESULTS/CONCLUSION: Ibandronate is rapidly absorbed and distributed in the bone;
      it is not metabolised and is excreted in urine. Clinical trial data have
      demonstrated the efficacy of ibandronate in reducing fracture risk, increasing
      bone mineral density and reducing bone turnover. These data are supported by
      recent meta-analyses and a large database study that have demonstrated
      antifracture efficacy with the ibandronate regimens used in clinical practice.
      Overall, ibandronate has generally been well tolerated. Therefore, ibandronate is
      a useful treatment for postmenopausal osteoporosis.

PMID- 18624682
TI  - An updated review of acitretin--a systemic retinoid for the treatment of
      psoriasis.
AB  - BACKGROUND: Acitretin is a systemic retinoid used for psoriasis. It normalizes
      cellular differentiation and maturation and is also used as a chemopreventive
      agent against cutaneous malignancies. However, it is not used frequently because
      of its side-effect profile. OBJECTIVE: Safety and efficacy of acitretin was
      evaluated as monotherapy, as well as in combination with other systemic agents.
      METHODS: Medical literature from 2005 to 2008 was reviewed. The most
      scientifically rigorous clinical trials were selected for Psoriasis Area and
      Severity Index. Articles were limited to case reports or clinical trials, human
      subjects and English language journals. RESULTS/CONCLUSION: Acitretin is
      effective as monotherapy for pustular and erythrodermic psoriasis and for plaque
      psoriasis (with other systemic agents). Side effects of acitretin use occur more
      commonly with high doses. Hence, acitretin is safe and effective for psoriasis.

PMID- 18624683
TI  - Efavirenz--still first-line king?
AB  - BACKGROUND: Efavirenz is a potent, safe and tolerable non-nucleoside reverse
      transcriptase inhibitor (NNRTI) recommended as initial therapy. Recently, several
      new antiretroviral drugs, including second generation NNRTIs, protease
      inhibitors, an integrase-inhibitor and a CCR5 inhibitor, have become or will be
      shortly available. OBJECTIVE: This article will review relevant efficacy and
      safety data of efavirenz compared to these novel agents or certain common
      alternate drugs currently used as initial therapy in treatment-naive patients.
      METHODS: Published articles and conference presentations pertaining to efavirenz
      and/or the newer antiretroviral agents were evaluated. RESULTS/CONCLUSIONS:
      Efavirenz will continue to be preferred initial therapy for now. If longer-term
      studies of integrase inhibitors and second-generation NNRTIs confirm initial
      findings, they will eventually supplant efavirenz as preferred first-line agents.

PMID- 18624684
TI  - Thalidomide in multiple myeloma--clinical trials and aspects of drug metabolism
      and toxicity.
AB  - BACKGROUND: After the tragic events in the early 1960s, thalidomide has re
      emerged as therapeutic for multiple myeloma (MM). It was first approved for the
      treatment of erythema nodosum leprosum, and is now under evaluation for
      hematologic and non-hematologic disorders. Its complex mechanism of action is not
      fully understood; however extensive preclinical studies in MM have revealed its
      antiangiogenic and immunomodulatory properties. OBJECTIVE: In this review, we
      focus on the importance and toxicity of thalidomide in today's clinical use.
      METHODS: Key preclinical and clinical trials available as well as data on the
      pharmacokinetics and pharmacodynamics of thalidomide in humans are summarized.
      CONCLUSIONS: Thalidomide is widely used as first-line treatment and in
      relapsed/refractory MM. The most common side effects are fatigue, constipation
      and peripheral neuropathy, and careful monitoring is required to avoid fetal
      exposure.

PMID- 18624685
TI  - Experience with exemestane in the treatment of early and advanced breast cancer.
AB  - BACKGROUND: Exemestane represents the only steroidal third-generation aromatase
      inactivator implemented for breast cancer therapy. OBJECTIVE: Present clinical
      and translational data defining the role of exemestane as an aromatase inhibitor.
      METHODS: Literature search including PubMed and ISI Web of Science.
      RESULTS/CONCLUSION: Exemestane potently inhibits in vivo aromatization resembling
      anastrozole and letrozole. Randomized trials have revealed superiority for
      exemestane compared to conventional therapy in metastatic breast cancer. In
      addition sequential treatment with tamoxifen (for 2 - 3 years) followed by
      exemestane (for 3 - 2 years) has revealed superiority with respect not only to
      relapse-free but also borderline improvement in overall survival in adjuvant
      therapy. Several studies now confirm lack of cross-resistance between non
      steroidal aromatase inhibitors and exemestane, which could be due to exemestane's
      low androgen-agonistic activity through its 17-hydro metabolite.

PMID- 18624686
TI  - Butenafine and superficial mycoses: current status.
AB  - BACKGROUND: Butenafine hydrochloride, a benzylamine derivative, exhibits potent
      fungicidal activity particularly against dermatophytes, aspergilli, dimorphic and
      dematiaceous fungi. OBJECTIVE: To review pharmacokinetics, mechanism of actions
      and clinical efficacy of butenafine against various dermatophytic and other
      superficial fungal infections. METHODS: Medline search was made using keyword
      butenafine. All English language articles were considered for this review. For
      inclusion in clinical efficacy section when ever available randomized controlled
      trials were considered a priority over other trials. RESULTS/CONCLUSIONS: The
      drug has excellent penetration into the epidermis and a prolonged retention time
      following topical application, conferring residual therapeutic activity after
      treatment cessation. Butenafine possess anti-inflammatory activity too. Topical
      butenafine 1% cream has been reported to be efficacious for tinea pedis, tinea
      corporis and tinea cruris in many randomized clinical trials when used for
      shorter duration. Its efficacy against pityriasis versicolor, seborrheic
      dermatitis and as anticandidal agent is not yet fully established.

PMID- 18624687
TI  - Lessons learned from development of docetaxel.
AB  - BACKGROUND: Docetaxel has benefited from focused evaluation of its preclinical
      pharmacology and pharmacokinetics, as well as the evolving areas that are
      becoming significant to cancer drug development: pharmacogenetics, population
      pharmacokinetics, and in vivo quantitative pharmacology. OBJECTIVE: This review
      juxtaposes the evolution of clinical use of docetaxel and the efforts to limit
      its observed clinical variability through understanding of its fundamental
      pharmacology. METHODS: The clinical review portion of this paper focuses on the
      examples of breast and lung cancer, to highlight the empiric process that have
      defined the current drug development process. The exploration of published
      reports on the clinical pharmacology of docetaxel is then reviewed to emphasize
      the rich resources available for future development of docetaxel in malignancy.
      RESULTS/CONCLUSION: As docetaxel moves forward in development, the knowledge
      gained in the evolution of docetaxel thus far can be leveraged in a model-based
      drug development schema to effectively use this body of data to make informed
      decisions about future dose/drug combinations and maximize the chance of further
      successes in the clinical arena.

PMID- 18624688
TI  - Sterols in red and green algae: quantification, phylogeny, and relevance for the
      interpretation of geologic steranes.
AB  - Steroids, a class of triterpenoid lipids with high preservation potential, are
      widely distributed in sedimentary rocks. All eukaryotes have a physiological
      requirement for these molecules, making steroids important biomarkers for aiding
      our understanding of eukaryote molecular evolution and geologic history. C(26)
      C(30) sterols are the molecules most commonly incorporated or synthesized by
      eukaryotes, and correspond to C(26)-C(30) steranes ubiquitously and abundantly
      preserved in petroleums and sedimentary bitumens. Because these sterols occur in
      evolutionarily diverse taxa, it can be difficult to associate any particular
      compound with a single group of organisms. Nevertheless, geochemists have still
      been able to draw parallels between the empirical patterns in geologic sterane
      abundances and the age of petroleum source rocks. Paleobiologists have also used
      sterane data, in particular the patterns in C(29) and C(28) steranes, to support
      fossil evidence of an early radiation of green algae in latest Proterozoic and
      Paleozoic and the succession of the major modern phytoplankton groups in the
      Mesozoic. Although C(29) sterols are found in many eukaryotes, organisms that
      produce them in proportional abundances comparable to those preserved in
      Proterozoic and Paleozoic rocks are limited. Based on a large, phylogenetically
      based survey of sterol profiles from the kingdom Plantae, we conclude that modern
      ulvophyte and early diverging prasinophyte green algae produce high abundances of
      C(29) relative to C(27) and C(28) sterols most consistent with the sterane
      profiles observed in Paleozoic rocks. Our analysis also suggests that ancestral
      stem groups among the Plantae, including the glaucocystophytes and early
      divergent red algae are also plausible candidates.

PMID- 18624689
TI  - Gedeon Dagan: a brief story of my life ...

PMID- 18624691
TI  - Some considerations in applying background concentrations to ground water
      studies.

PMID- 18624692
TI  - Long-term trends in chloride concentrations in shallow aquifers near Chicago.
AB  - The rapid expansion of major cities throughout the world is resulting in the
      degradation of water quality in local aquifers. Increased use of road deicers
      since the middle of the 20th century in cities in the northern United States,
      Canada, and Europe has been linked to degraded ground water quality. In this
      article, Chicago, Illinois, and its outlying suburban areas are used as an
      example of the effects of urbanization in a historical context. A statistical
      study of historical water quality data was undertaken to determine how
      urbanization activities have affected shallow (<60 m) ground water quality.
      Chloride (Cl(-)) concentrations have been increasing, particularly in counties
      west and south of Chicago. In the majority of shallow public supply wells in the
      western and southern counties, Cl(-) concentrations have been increasing since
      the 1960s. About 43% of the wells in these counties have rate increases greater
      than 1 mg/L/year, and 15% have increases greater than 4 mg/L/year. Approximately
      24% of the samples collected from public supply wells in the Chicago area in the
      1990s had Cl(-) concentrations greater than 100 mg/L (35% in the western and
      southern counties); median values were less than 10 mg/L before 1960. The greater
      increase in Cl(-) concentrations in the outer counties is most likely due to both
      natural and anthropogenic factors, including the presence of more significant and
      shallower sand and gravel deposits, less curbing of major highways and streets,
      and less development in some parts of these counties.

PMID- 18624693
TI  - Using MODFLOW 2000 to model ET and recharge for shallow ground water problems.
AB  - In environments with shallow ground water elevation, small changes in the water
      table can cause significant variations in recharge and evapotranspiration fluxes.
      Particularly, where ground water is close to the soil surface, both recharge and
      evapotranspiration are regulated by a thin unsaturated zone and, for accuracy,
      must be represented using nonconstant and often nonlinear relationships. The most
      commonly used ground water flow model today, MODFLOW, was originally designed
      with a modular structure with independent packages representing recharge and
      evaporation processes. Systems with shallow ground water, however, may be better
      represented using either a recharge function that varies with ground water depth
      or a continuous recharge and evapotranspiration function that is dependent on
      depth to water table. In situations where the boundaries between recharging and
      nonrecharging cells change with time, such as near a seepage zone, a continuous
      ground water flux relationship allows recharge rates to change with depth rather
      than having to calculate them at each stress period. This research article
      describes the modification of the MODFLOW 2000 recharge and segmented
      evapotranspiration packages into a continuous recharge-discharge function that
      allows ground water flux to be represented as a continuous process, dependent on
      head. The modifications were then used to model long-term recharge and
      evapotranspiration processes on a saline, semiarid floodplain in order to
      understand spatial patterns of salinization, and an overview of this process is
      given.

PMID- 18624694
TI  - Risk management of BTEX contamination in ground water--an integrated fuzzy
      approach.
AB  - Abstract An integrated fuzzy simulation-assessment method (FSAM) was developed
      for assessing environmental risks from petroleum hydrocarbon contamination in
      ground water. In the FSAM, techniques of fuzzy simulation and fuzzy risk
      assessment were coupled into a general framework to reflect a variety of system
      uncertainties. A petroleum-contaminated site located in western Canada was
      selected as a study case for demonstrating applicability of the proposed method.
      The risk assessment results demonstrated that system uncertainties would
      significantly impact expressions of risk-level outputs. A relatively
      deterministic expression of the risks would have clearer representations of the
      study problem but may miss valuable uncertain information; conversely, an
      assessment under vaguer system conditions would help reveal potential
      consequences of adverse effects but would suffer from a higher degree of
      fuzziness in presenting the modeling outputs. Based on the risk assessment
      results, a decision analysis procedure was used to calculate a general risk index
      (GRI) to help identify proper responsive actions. The proposed method was useful
      for evaluating risks within a system containing multiple factors with complicated
      uncertainties and interactions and providing support for identifying proper site
      management strategies.

PMID- 18624695
TI  - Simulating a lake as a high-conductivity variably saturated porous medium.
AB  - One approach for simulating ground water-lake interactions is to incorporate the
      lake into the ground water solution domain as a high-conductivity region.
      Previous studies have developed this approach using fully saturated models. This
      study extends this approach to variably saturated models, so that ground water
      lake interactions may be more easily simulated with commonly used or public
      domain variably saturated codes that do not explicitly support coupled lake-water
      balance modeling. General guidelines are developed for the choices of saturated
      hydraulic conductivity and moisture retention and relative permeability curves
      for the lake region. When applied to an example ground water-lake system, model
      results are very similar to those from a model in which the lake is represented
      as a specified head boundary continuously updated by a lake mass balance. The
      high-conductivity region approach is most suitable for relatively simple
      geometries and lakes with slower and smaller fluctuations when the overall flow
      pattern and system fluxes, rather than the detailed flow pattern around the
      intersection of the lake and land surfaces, are of interest.

PMID- 18624696
TI  - Clinical efficacy in bleeding and surgery in von Willebrand patients treated with
      Fanhdi a highly purified, doubly inactivated FVIII/VWF concentrate.
AB  - Therapy with factor VIII/von Willebrand factor (FVIII/VWF) concentrate is the
      mainstay therapy in patients with von Willebrand disease (VWD) unresponsive to
      desmopressin. There are several commercially available FVIII/VWF concentrates
      that have been tested in VWD patients. We retrospectively analized the clinical
      efficacy in bleeding episodes and surgery of a highly purified FVIII/VWF complex
      with two inactivation steps (Fanhdi) in VWD patients. Sixty patients were
      included in the study. Treatment schedule consisted of one or more doses
      (standard dose 40 IU/kg body weight of FVIII) of Fanhdi. One hundred and fifty
      bleeding episodes were treated. These were: 28 serious bleedings; 92 moderate and
      30 mild. An excellent clinical efficacy in almost 95% of cases was observed.
      Fanhdi was administered during 66 surgical procedures (38 major and 28 minor)
      with an overall efficacy of 98%. Fanhdi a highly purified, doubly virus
      inactivated FVIII/VWF concentrate, with a high content of active VWF and an
      excellent record of clinical safety, is a valid choice in treating VWD.

PMID- 18624697
TI  - Pulmonary embolus in Glanzmann's thrombasthenia treated with warfarin.

PMID- 18624698
TI  - Identification of mutations in the F9 gene including exon deletion by multiplex
      ligation-dependent probe amplification in 33 unrelated Korean patients with
      haemophilia B.
AB  - Haemophilia B (HB) is a rare X-linked recessive bleeding disorder caused by a
      mutation in the F9 gene. The aims of this study were to characterize the mutation
      spectrum of F9 in Korean patients with HB to establish the optimal molecular
      diagnostic strategy and to find genotype-phenotype correlations. Study subjects
      consisted of 33 unrelated Korean patients with HB. We performed polymerase chain
      reaction (PCR) amplification and direct sequencing of all exons and flanking
      sequences of F9. When large deletion was suspected from PCR failure, exon dosage
      test using multiplex ligation-dependent probe amplification (MLPA) was performed.
      We identified disease-causing mutations in 32 out of 33 patients by direct
      sequencing analyses (mutation detection rate, 97%). A total of 28 unique
      mutations were detected, including 7 novel ones. Six mutations were recurrent but
      observed in no more than two patients. In the remaining one patient, exon 1 was
      not amplified, and MLPA analysis confirmed a large deletion involving exon 1. The
      genotype-phenotype correlations between the type of mutation and the severity of
      factor deficiency were not consistent, as has been previously reported. One
      patient developed inhibitor, and he was the patient with exon 1 deletion. Based
      on our results from 33 Korean patients with HB, which showed no hotspot for
      mutations, direct sequencing of all exons with flanking sequences is needed as
      the first-line test. MLPA can be a feasible platform at clinical laboratories to
      detect large deletion mutations in suspected cases.

PMID- 18624699
TI  - Mission of World Federation of Haemophilia, Biotechnology and treatment for all?
      The paradox.

PMID- 18624700
TI  - Endothelial dysfunction in haemophilia patients.
AB  - Haemophilia patients may develop cardiovascular diseases, suggesting that their
      clotting defect does not protect them completely from atherosclerosis and its
      complications. We aimed to evaluate cardiovascular risk factors and, for the
      first time, the presence of endothelial dysfunction in middle-aged haemophilia
      patients. We studied 40 patients with haemophilia A and B (24 with moderate
      severe disease and 16 with mild disease), and 40 healthy controls. Flow-mediated
      dilation (FMD), carotid ultrasound (US) intima media thickness (IMT), arterial
      blood pressure, body mass index (BMI), cholesterol, triglycerides, glucose,
      insulin, lipoprotein(a) and homocysteine levels were measured, and PAI-1 and t-PA
      levels before and after venous occlusion (VO), and antibodies to HIV, HBV and HCV
      were assayed. At least one cardiovascular risk factor was detected in 87.5% of
      patients, and 2 or more in 47.5% of cases. At US exam, none of the patients had
      significant carotid stenosis or significant differences in IMT compared to
      controls. In contrast, all the patients had a significant FMD impairment,
      associated with a reduced t-PA release after VO in 70% of cases. PAI-1 levels
      significantly correlated with BMI, triglycerides and insulin values. Fifteen
      haemophilia patients with chronic viral hepatitis and/or HIV infection showed a
      significantly lower FMD than patients without active infection. We found an
      endothelial dysfunction with impaired FMD and t-PA release in our haemophilia
      patients, usually associated with cardiovascular risk factors. Other pathogenic
      mechanisms, such as chronic viral infections, are likely to be involved in this
      endothelial damage, however.

PMID- 18624701
TI  - Patients' and their family members' understanding of the genetics of type 1 von
      Willebrand disease.

PMID- 18624702
TI  - Quality of life, psychosocial strains and coping in parents of children with
      haemophilia.
AB  - Quality of life in parents of children suffering from haemophilia may be
      diminished by the illness burden experienced in daily life and by non-adaptive
      ways of coping. The aim of this study was to examine the relation between
      parents' quality of life, their perceived psychosocial strains and ways of
      coping, and to compare parents' outcome to other paediatric illness groups
      (juvenile idiopathic arthritis, type 1 diabetes). In a cross-sectional study,
      parents completed a questionnaire concerning quality of life, psychosocial
      strains, coping strategies and needs as well as sociodemographic and illness
      parameters. Study participants were recruited in an ambulant haemophilia centre.
      A total of 55 parents (32 mothers, 23 fathers; age = 39.6; SD = 8.6) of children
      suffering from haemophilia (age = 11.0; SD = 6.4) took part in the study.
      Comparison groups were parents of children with juvenile idiopathic arthritis (n
      = 161) and parents of children with type 1 diabetes (n = 69). Compared to parents
      from other paediatric illness groups, the parents of children with haemophilia
      experience less impact on their quality of life and lower psychosocial strains.
      Quality of life was predicted by the coping strategy 'improving marital
      relationship' (beta = 0.48) and by emotional strains and worries concerning
      future (beta = -0.43; explained variance 49%). Parents reported a pronounced need
      for further information on the comprehensive management of haemophilia. In the
      psychosocial care of families with a child suffering from -haemophilia, reducing
      psychosocial strains and strengthening adaptive coping strategies may be a
      preventive intervention for improving parents' quality of life.

PMID- 18624703
TI  - Successful use of recombinant FVIIa (Novoseven) in the management of uncontrolled
      bleeding after emergency fasciotomy.

PMID- 18624704
TI  - A pilot study on the effects of the transition of paediatric to adult health care
      in patients with haemophilia and in their parents: patient and parent worries,
      parental illness-related distress and health-related Quality of Life.
AB  - The aim of this pilot study was to investigate the effects of the transition from
      paediatric to adult health care services in haemophilia patients and their
      parents. We compared pretransition children (n = 9) and their parents (n = 18) to
      posttransition patients (n = 8) and their parents (n = 21). Pre- and
      posttransition patients did not differ in self-rated health-related quality of
      life (QoL) or worries about the transition. Fathers of posttransition patients
      rated their son's QoL as poorer than those of pretransition patients (P = 0.034)
      and indicated higher levels of illness-related distress than fathers of
      pretransition patients (P = 0.034). The findings indicate that the transition
      affects parents more than patients. Moreover, we found gender differences in
      parental worries about the transition. The findings indicate that programmes
      designed to facilitate the transition in haemophilic patients should also address
      the patients' parents.

PMID- 18624706
TI  - Headache is not a predominant symptom for bird flu.

PMID- 18624705
TI  - Efficacy of different doses of recombinant activated factor VII in the treatment
      of haemophilia children with inhibitor.

PMID- 18624707
TI  - Benign Raeder syndrome evolving into indomethacin-responsive hemicranial
      headache.
AB  - Benign Raeder syndrome is characterized by a self-limiting unilateral continuous
      headache associated with ipsilateral ptosis, miosis, and frequently, facial
      hypohydrosis. Hemicrania continua is a chronic, strictly unilateral continuous
      headache associated with ipsilateral cranial autonomic symptoms. We report a 50
      year-old man who presented with benign Raeder syndrome, which evolved into an
      indomethacin-responsive hemicranial headache that resembled hemicrania continua.

PMID- 18624708
TI  - Oxygen therapy influences episodic cluster headache and related cutaneous brush
      and cold allodynia.
AB  - Cluster headache (CH) is characterized by a series of sudden attacks of short
      lasting severe headache pain with ipsilateral autonomic features, including
      lacrimation, rhinorrhea, localized sweating, eyelid edema, and partial or
      complete Horner's syndrome. Just like in migraine, brush allodynia has been
      described for CH and for short lasting unilateral neuralgiform headache with
      conjunctival injection and tearing (SUNCT) syndrome. Administration of normobaric
      oxygen is part of the standard therapy for CH attacks. Here, we describe a young
      male with a first CH attack and the influence of oxygen on pain and concomitant
      cutaneous allodynia.

PMID- 18624710
TI  - Headache disability in orofacial pain patients is related to traumatic life
      events.
AB  - BACKGROUND: Headache is commonly reported in patients presenting with orofacial
      pain. It has only recently been demonstrated that headache-related disability is
      high in orofacial pain patients. Traumatic life events (TLEs) such as sexual
      abuse, physical abuse, and post-traumatic stress disorder (PTSD) are also common
      in orofacial pain patients and in the same patients reporting headache. In
      association with a previously reported study of headache disability in orofacial
      pain patients, it was noted that Migraine Disability Assessment (MIDAS) scores
      appeared to be significantly higher in patients with TLEs. OBJECTIVES: To
      investigate the relationship between TLEs and headache disability in a clinic
      population of orofacial pain patients. DESIGN: Retrospective study. METHODS: Four
      hundred and twenty-six consecutive orofacial pain patient records were reviewed,
      composed of new patients seen at the Orofacial Pain Center, National Naval
      Medical Center, Bethesda, MD, from November 2003 through December 2004. RESULTS:
      Of 426 orofacial pain patients reporting headache, 109 or 41.7% reported TLEs. In
      patients with TLEs, the mean MIDAS score was 28.81 +/- 37.2 compared with 13.5 +/
      17.9 for patients not reporting TLEs P < .000. MIDAS scores were significantly
      correlated with TLEs, Spearman correlation coefficient 0.272, P < .010.
      CONCLUSIONS: This is the first study to demonstrate that headache disability is
      significantly higher in a group of orofacial pain patients with TLEs and is
      correlated with that report of traumatic events. These findings clearly
      demonstrate the necessity for providers to consider a history of TLEs in
      orofacial pain patients presenting with headache.

PMID- 18624711
TI  - Familial hemiplegic migraine with prolonged aura and multimodality imaging: a
      case report.
AB  - We report a case of familial hemiplegic migraine with prolonged aura where
      multimodality imaging showed hemispheric cytotoxic edema along with evidence of
      hypometabolism in the affected hemisphere while there was no evidence of
      hypoperfusion of the affected hemisphere demonstrating that neuronal depression
      is a more plausible explanation in its pathogenesis.

PMID- 18624712
TI  - Socio-economic factors, lifestyle, and headache disorders - a population-based
      study in Sweden.
AB  - OBJECTIVE: To study the association between socio-economic factors, lifestyle
      habits, and self-reported recurrent headache/migraine (RH/M) in a general
      population. METHODS: The study population comprised a random sample of men and
      women aged 18-79 years. The data were obtained using a postal survey
      questionnaire during March-May 2000. The overall response rate was 65%. The area
      investigated covers 58 municipalities with about one million inhabitants in
      central part of Sweden. The study is based on 43,770 respondents. Odds ratios for
      RH/M were calculated for a set of variables using multiple logistic regression
      models. RESULTS: The overall prevalence of self-reported RH/M during the last 3
      months was 10% among men and 23% among women and decreased with increasing age.
      Physically inactive subjects were more likely to suffer from headache disorders
      than physically active subjects. Smoking was only moderately associated with
      RH/M. There was an inverse relationship between heavy alcohol use and RH/M.
      Underweight and obesity were not associated with headache disorders when adjusted
      for socio-economic factors. Subjects with frequent economic problems had almost
      twice the risk of RH/M compared with subjects with no economic problems. Poor
      social support was associated with headache disorders and subjects who had been
      belittled during the last 3 months were more than twice as likely to suffer from
      RH/M as subjects who had not been belittled. The effect of educational level was
      modest. Marital status and country of origin were not associated with headache
      disorders after adjustment for other socio-economic factors. Dissatisfaction with
      work, worry about losing one's job, and absenteeism due to illness were strongly
      associated with headache disorders. Physical working conditions and working hours
      were not associated with RH/M. CONCLUSION: Headache disorders mainly affect young
      and middle-aged adults. There are, however, socio-economic disparities in self
      reported recurrent headache and migraine. The relationship was particularly
      evident for economic hardship and psychosocial factors. Of lifestyle factors,
      physical inactivity was strongly associated with headache disorders independent
      of economic and psychosocial factors.

PMID- 18624713
TI  - Familial clustering of migraine: further evidence from a Portuguese study.
AB  - OBJECTIVE: Our aim was to evaluate familial aggregation of migraine in a large
      group of Portuguese families, and to assess if familial aggregation differs
      between MA and MO. METHODS: Familial aggregation was evaluated by estimating
      relative risk (RR) of migraine in 143 first-degree relatives of 50 probands with
      MA, in 196 first-degree relatives of 94 probands with MO and also in proband's
      spouses. Probands were enrolled in the study from a clinical sample and a
      population sample was used as reference. RESULTS: A significantly increased risk
      of migraine was found in both first-degree relatives of MO probands (RR = 3.7;
      95% CI: 3.2-4.3) and of MA probands (RR = 3.6; 95% CI: 3.1-4.3), comparatively to
      the general population. Risk for spouses was not increased. First-degree
      relatives of MA probands and MO probands had a significantly increased risk of
      both MA and MO compared to the general population. In the group of MA probands,
      RR of MA in first-degree relatives reached a significant 4-fold increase when
      compared with RR of MO (RR(MA|MA) = 12.2, 95%CI: 7.7-19.5; RR(MO|MA) = 3.1,
      95%CI: 2.5-3.8), while, in the group of MO probands, RR of MA was not
      significantly increased when compared with RR of MO (RR(MA|MO) = 5.3, 95%CI: 3.1
      9.2; RR(MO|MO) = 4.0, 95%CI: 3.5-4.7). CONCLUSIONS: The present study focus on
      familial aggregation of migraine in a Portuguese population. Our results
      demonstrate a substantial familial risk of migraine with evidence of both common
      and specific etiologic mechanisms for either migraine subtypes.

PMID- 18624715
TI  - Transient elastography: Applications and limitations.
AB  - Transient elastgraphy with use of FibroScan is one of most accurate methods for
      assessment of liver fibrosis. FibroScan can be readily used with an operator with
      a short training. In many different studies, liver stiffness measured by
      transient elastgraphy correlates well with fibrosis stages, and cutoff values of
      liver stiffness for fibrosis staging are similar even among different diseases.
      However there is wide variation of stiffness values in the same fibrosis stage,
      and some overlap between the adjacent stages. In addition, inflammatory activity
      and size of nodule of cirrhosis affect the liver stiffness values. The
      reproducibility may be reduced by age, obesity, steatosis, narrow intercostal
      space and lower degrees of hepatic fibrosis in patients. Thus the estimation of
      fibrosis stages from liver stiffness should be cautiously done. To improve the
      accuracy of liver fibrosis staging, the combination of transient elastography
      with other noninvasive methods such as FibroTest should be required.

PMID- 18624714
TI  - Are sleep difficulties associated with migraine attributable to anxiety and
      depression?
AB  - OBJECTIVE: To examine whether sleep complaints reported by migraineurs can be
      attributed to comorbid anxiety and/or depression. BACKGROUND: A consistent
      association between migraine and sleep complaints has been reported in community
      and clinical studies. However, anxiety and depression are often comorbid with
      migraine. Thus, it may be possible that the increased prevalence of sleep
      problems in migraineurs is attributable to comorbid anxiety and depression. To
      our knowledge, no previous studies have demonstrated that the associations are
      not solely attributed to comorbid anxiety and depression. DESIGN AND METHODS:
      Controlled family study of anxiety disorders and substance use disorders in a
      community in New Haven County, CT. The sample included 221 probands (41
      migraineurs) and their 261 directly interviewed first-degree relatives (39
      migrainuers), including parents, siblings, and offspring over age 18. A lifetime
      history of migraine was obtained using the Diagnostic Interview for Headache
      Syndromes. A lifetime history of psychiatric disorders was obtained using the
      semi-structured Schedule for Affective Disorders and Schizophrenia which was
      modified to incorporate Diagnostic and Statistical Manual diagnostic criteria.
      Several sleep items on current and lifetime sleep complaints were included as a
      subset of the interview. RESULTS: There was a significant association between
      migraine and the number of sleep problems as well as several specific sleep
      symptoms among probands and their adult relatives. Adults with migraine reported
      having significantly more lifetime sleep problems (OR [CI] = 2.3 [1.1-4.6]), and
      more current sleep difficulties, specifically, inadequate sleep (2.5 [1.2-5.0]),
      difficulty falling asleep (3.0 [1.5-6.3]), and persistent nightmares of childhood
      onset (4.3 [1.8-9.9]) than those without migraine. The associations between sleep
      problems and migraine persisted after controlling for both lifetime and current
      anxiety and mood disorders. CONCLUSIONS: The association between sleep problems
      and migraine that is not solely explained by comorbid anxiety disorders or
      depression suggests that sleep problems should be evaluated among people with
      migraine.

PMID- 18624716
TI  - Up-regulation of breast cancer resistance protein expression in hepatoblastoma
      following chemotherapy: A study in patients and in vitro.
AB  - AIM: Hepatoblastoma (HB), the most common pediatric malignant liver tumor, is
      treated with chemotherapy to facilitate surgical resection. Previous studies
      suggest that HB acquires chemoresistance via increased expression of multidrug
      resistance protein 1 (MDR1, ABCC1). There is no well established evidence that
      this also occurs in the clinical setting and little is known about the effects of
      chemotherapeutic treatments on HB in situ. METHODS: Clinical and
      histopathological features and expression patterns of ABC transporters in
      diagnostic needle biopsies from 7 HBs taken before chemotherapy were compared
      with those in surgically resected tumors. To understand the mechanisms leading to
      chemoresistance we also investigated the involvement of hypoxia on protein
      expression and functional activity of drug transporters (BCRP and MDR1) in
      cultures of HepG2 human HB cells. RESULTS: We found that chemotherapeutical
      treatment of HBs led to an increased expression of the breast cancer resistance
      protein (BCRP, ABCG2) in all patients studied. There was no change in the
      expression pattern of MDR1 or other ABC transporters. Chemotherapy-induced
      specific vascular abnormalities associated with areas of necrosis and fibrosis
      were seen in all cases, suggesting tumor hypoxia. The observations of increased
      BCRP expression in hypoxic areas of three-dimensional HepG2 aggregates and the
      enhanced BCRP function in monolayer cultures of HepG2 cells under hypoxic
      conditions, support a role for hypoxia in enhanced BCRP expression. CONCLUSIONS:
      Chemotherapeutical treatment of HB leads to vascular alterations that modify the
      tumor microenvironment, and increased BCRP expression in which hypoxia might play
      a role. No evidence was found for upregulation of MDR1 in HBs as suggested from
      previous experimental studies.

PMID- 18624717
TI  - Griseofulvin, an oral antifungal agent, suppresses hepatitis C virus replication
      in vitro.
AB  - AIM: Hepatitis C virus (HCV), which infects an estimated 170 million people
      worldwide, is a major cause of chronic liver disease. The current standard
      therapy for chronic hepatitis C is based on pegylated interferon (IFN)alpha in
      combination with ribavirin. However, the success rate remains at approximately
      50%. Therefore, alternative agents are needed for the treatment of HCV infection.
      METHODS: Using an HCV-1b subgenomic replicon cell culture system (Huh7/Rep-Feo),
      we found that griseofulvin, an oral antifungal agent, suppressed HCV-RNA
      replication and protein expression in a dose-dependent manner. We also found that
      griseofulvin suppressed the replication of infectious HCV JFH-1. A combination of
      IFNalpha and griseofulvin exhibited a synergistic inhibitory effect in Huh7/Rep
      Feo cells. RESULTS: We found that griseofulvin blocked the cell cycle at the
      G(2)/M phase in the HCV subgenomic replicon cells, but did not inhibit HCV
      internal ribosome entry site-dependent translation. CONCLUSION: Our results
      suggest that griseofulvin may represent a new approach to the development of a
      novel therapy for HCV infection.

PMID- 18624718
TI  - Deficiency of forkhead box P3 and cytotoxic T-lymphocyte-associated antigen-4
      gene expressions and impaired suppressor function of CD4(+)CD25(+) T cells in
      patients with autoimmune hepatitis.
AB  - AIM: Recently, forkhead box P3 (Foxp3), cytotoxic T-lymphocyte-associated antigen
      4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related
      gene (GITR), and CD28 were identified as the key molecules that control the
      development and activation of CD4+CD25+ regulatory T cells (T-reg). We
      investigated the expression pattern of these molecules on T-reg, and investigated
      the ability of T-reg to produce cytokines in patients with autoimmune hepatitis
      (AIH). METHODS: Fifteen patients with AIH and nine healthy patients were
      included. To determine the frequency of T-reg, a two-color flow cytometry
      analysis was performed. T-reg were isolated using immunomagnetic beads, and the
      mRNA levels of Foxp3, CTLA-4, GITR, and CD28 were quantified by real-time
      polymerase chain reaction (PCR). The ability of T-reg to produce interferon
      gamma, interleukin (IL)-10, transforming growth factor-beta, and tumor necrosis
      factor-alpha after stimulation by OKT3 was evaluated by measuring the levels of
      mRNA in T-reg by real-time PCR. RESULTS: The frequency of T-reg was increased in
      AIH. The mRNA levels of Foxp3 and CTLA-4 were significantly lower in AIH. The
      ability of T-reg to produce IL-10 was impaired in AIH. CONCLUSION: We speculate
      that the inferiority of the Foxp3 and CTLA-4 gene expressions on T-reg results in
      the impaired suppressor function of T-reg, and eventually in the breakdown of
      self-tolerance.

PMID- 18624719
TI  - Occult hepatitis B virus infection in HIV-infected patients: Evaluation of
      biochemical, virological and molecular parameters.
AB  - AIM: To determine the prevalence of occult hepatitis B virus (HBV) infection in a
      group of human immunodeficiency virus (HIV)-infected Brazilian patients and to
      investigate its association with biochemical, virological and molecular features.
      METHODS: Sera from 43 patients positive for HBV core antibody and negative for
      HBV surface antigen (HBsAg) were tested for HBV DNA positivity by semi-nested
      PCR. HBV loads were assessed by real-time PCR. S gene was cloned and sequenced
      for HBV isolates from 3 patients. HBsAg expression of these cases was performed
      in HuH7 cells. RESULTS: HBV DNA was found in 6/43 (14%) samples, all except one
      associated with low viral loads. Occult HBV infection was further correlated with
      anti-hepatitis C virus (anti-HCV) antibodies positivity, but not with alanine
      aminotransferase (ALT) elevated levels. S gene sequences derived from three
      patients were determined. Two of them displayed mutations that may explain HBsAg
      negativity. In the first one, a stop codon mutation was found at position 216 in
      the C-terminal end of HBsAg. In the second patient, E164D and I195M substitutions
      in HBsAg, associated with lamivudine-resistance mutations in the polymerase were
      identified. As expected, all clones showing those mutations displayed
      undetectable or very low levels of HBsAg. CONCLUSION: Occult HBV infection was
      frequent in HIV-infected patients, was not associated with ALT elevation but
      significantly correlated with HCV seropositivity. The low viremia and the
      detection of HBsAg mutants confirm that multifactorial mechanisms are involved in
      occult HBV infection. HBV molecular monitoring should be employed for an adequate
      management of HBV/HIV co-infected patients.

PMID- 18624720
TI  - Reply.

PMID- 18624721
TI  - Biliary reconstruction in right lobe living donor liver transplantation.

PMID- 18624722
TI  - Activation of B-Myb by E2F1 in hepatocellular carcinoma.
AB  - AIM: Deregulation of E2F1 transcriptional activity is observed in a variety of
      cancers, including hepatocellular carcinoma (HCC). The aim of the present study
      is to identify transcriptional target genes of E2F1 in HCC. METHODS: We
      determined expression levels for E2F1 and ten candidate genes thought to be
      targets of E2F1 in primary HCCs using a real-time quantitative reverse
      transcription-PCR assay. Following small interfering RNA (siRNA)-mediated
      knockdown of E2F1 in HCC cell lines, we quantified mRNA levels of the candidate
      E2F1 target genes. RESULTS: E2F1 was significantly over-expressed in 41 primary
      HCCs as compared to non-tumorous liver tissues. Among the candidates, MYBL2,
      whose product is the transcriptional factor B-Myb, which is involved in
      controlling cell-cycle progression and apoptosis, was significantly over
      expressed in primary HCCs. Additionally, expression levels of MYBL2 correlated
      with those of E2F1. Knockdown of E2F1 resulted in a decrease in expression of
      MYBL2. A copy-number gain for MYBL2 was observed in 36 of 66 primary HCCs,
      suggesting that MYBL2 expression is up-regulated by amplification in addition to
      being regulated by E2F1. Moreover, siRNA-mediated knockdown of MYBL2 led to
      reduced expression of CDC2 (which encodes CDC2), cyclin A2 (CCNA2), and
      topoisomerase II alpha (TOP2A), implicating these genes in the cell cycle and
      suggesting that they may be downstream targets of B-Myb. CONCLUSION: MYBL2 is a
      probable transcriptional target of E2F1 in HCC and may therefore be a useful
      biomarker for diagnosis and an attractive target for molecular therapies useful
      to treat HCC.

PMID- 18624723
TI  - Amoebiasis among patrons visiting gay saunas in Taiwan.
AB  - AIMS: This study aimed to assess the prevalence of amoebiasis among patrons
      visiting gay saunas in Taiwan. METHODS: A cross-sectional survey was conducted
      using questionnaire interview and indirect hemagglutination assays and specific
      Entamoeba histolytica antigen assays of blood and rectal swab specimens,
      respectively, among patrons visiting 10 gay saunas between September 2006 and
      December 2006. RESULTS: During the three-month study period, 208 blood and 120
      rectal swab specimens were tested for E. histolytica infection. Amoebiasis was
      detected among 3.8% and 3.3% of the patrons by serologies and antigen assays,
      respectively. During the latest sexual encounter, more than 70% of the patrons
      had oral-anogenital sex, and only 20% used condoms during oral-anogenital
      contact. CONCLUSION: Our findings suggest that there is a potential risk of E.
      histolytica transmission among the patrons visiting gay saunas who do not
      practise safe sex consistently in Taiwan.

PMID- 18624724
TI  - Recovery of fat following a switch to nucleoside reverse transcriptase inhibitor
      sparing therapy in patients with lipoatrophy: results from the 96-week randomized
      ANRS 108 NoNuke Trial.
AB  - OBJECTIVES: To evaluate the impact on peripheral fat tissue of a nucleoside
      reverse transcriptase inhibitor (NRTI)-sparing regimen in lipoatrophic HIV-1
      infected patients. METHODS: This 96-week prospective, randomized study compared
      lipoatrophic patients switched to an NRTI-sparing regimen with patients remaining
      on an NRTI-containing regimen. The primary endpoint was the change in thigh
      subcutaneous fat tissue volume between baseline and week 48, as assessed by
      computerized tomography. RESULTS: One hundred patients were included, 50 in each
      arm. At baseline, patients had been on highly active antiretroviral therapy
      (HAART) for a median time of 6.6 years (4.9-9.7); 71% of the patients had
      received thymidine analogues [stavudine (37%), zidovudine (34%)]. The mean change
      in fat volume between baseline and week 48 significantly favoured the NRTI
      sparing arm over the NRTI-maintaining arm in the intent-to-treat analysis, with a
      last-observation-carried-forward approach [+34 cm(3); 95% confidence interval
      (CI) 5-63 cm(3); P=0.002]. This was confirmed in the intent-to-treat analysis of
      available data, with a mean difference of +109 cm(3) (95% CI 34-185 cm(3)) at
      week 96 (n=53; P=0.001). This corresponded to increases of 12 and 30% in fat
      volume at weeks 48 and 96, respectively, in the NRTI-sparing arm. CONCLUSIONS:
      Switching from an effective NRTI-containing regimen to an NRTI-sparing regimen
      preserves immunovirological status and increases subcutaneous fat volume at weeks
      48 and 96.

PMID- 18624725
TI  - The immunomodulatory activity of human umbilical cord blood-derived mesenchymal
      stem cells in vitro.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSC) are currently being
      investigated in preclinical and clinical settings because of their self-renewal
      and multipotent differentiative capacity or their immunosuppressive function.
      However, BM may be detrimental because of the highly invasive donation procedure
      and BM-MSC decline with age. Therefore, MSC derived from other sources have been
      considered as an alternative. However, there is only limited knowledge on their
      immunomodulatory properties. Human umbilical cord blood (UCB) cells are good
      substitutes for BM-MSC because of the immaturity of newborn cells. In this study,
      we successfully isolated MSC from UCB. The morphological phenotypes, cell cycle
      status, surface markers and differentiation potential of these clonally expanded
      cells are consistent with BM-MSC. Furthermore, UCB-MSC expanded in vitro retain
      low immunogenicity and an immunomodulatory effect. Flow cytometry analysis showed
      that UCB-MSC did not express CD40, CD40 ligand, CD80, CD86 and major
      histocompatibility complex class II molecules. We have demonstrated that UCB-MSC
      are incapable of inducing allogeneic peripheral blood mononuclear cell (PBMC)
      proliferation and have a dose-dependent inhibition of PBMC immune responses in
      mixed lymphocyte reactions (MLR) and phytohaemagglutinin activation assays, even
      after interferon-gamma treatment. Additionally, we have found that UCB-MSC can
      suppress the function of mature dendritic cells. Using transwell systems, we have
      demonstrated an inhibition mechanism that depends on both cell contact and
      soluble factors. Based on the findings we conclude that banked UCB could serve as
      a potential alternative source of MSC for allogeneic application in the future.

PMID- 18624726
TI  - Fatty acid-induced induction of Toll-like receptor-4/nuclear factor-kappaB
      pathway in adipocytes links nutritional signalling with innate immunity.
AB  - To study the effects of fatty acids and the involvement of the Toll-like receptor
      4/nuclear factor-kappaB (TLR-4/NF-kappaB) pathway with respect to the secretion
      of adipokines from adipocytes 3T3-L1 adipocytes were stimulated with increasing
      doses of fatty acids. The secretion of adiponectin, resistin and monocyte
      chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent
      assay. The NF-kappaB p65 nuclear translocation and TLR-4 expression were
      investigated by Western blot. The effects mediated by NF-kappaB were tested using
      a specific NF-kappaB-inhibitor and TLR-4-induced effects were analysed with a
      neutralizing TLR-4 antibody. Binding of (14)C-labelled fatty acids to TLR-4/MD-2
      was investigated using a FLAG-tagged extracellular part of TLR-4 fused to full
      length MD-2 via a linker (lipopolysaccharide-Trap). The messenger RNA (mRNA)
      expression of adipokines in abdominal adipose tissue of rats fed a standard chow
      or a high-fat diet was investigated by reverse transcription-polymerase chain
      reaction. The TLR-4 is induced during adipocyte differentiation and its
      expression is enhanced following fatty acid stimulation. The stimulatory effects
      of stearic and palmitic acids on MCP-1 secretion and of palmitoleic acid on
      resistin secretion are mediated via NF-kappaB. The stimulatory effects of
      stearic, palmitic and palmitoleic acids on resistin secretion and the stimulatory
      effect of stearic acid on MCP-1 secretion are mediated via TLR-4. Fatty acid
      mediated effects are caused by an endogenous ligand because fatty acids were
      shown not to bind directly to TLR-4/MD-2. Adipose tissue mRNA expression and
      serum levels of adipokines did not differ in rats fed a high-fat diet. These data
      provide a new molecular mechanism by which fatty acids can link nutrition with
      innate immunity.

PMID- 18624727
TI  - The T-cell pool is anergized in patients with multiple sclerosis in remission.
AB  - Relapsing-remitting multiple sclerosis (RRMS) is a complex autoimmune disease of
      the central nervous system with oscillating phases of relapse and remission. RRMS
      has been considered to be driven by T helper type 1 (Th1) lymphocytes but new
      data indicate the involvement of Th17 responses. In the present study, blood
      samples from patients (n=48) and healthy individuals (n=44) were evaluated for
      their immunological status. T cells from patients with RRMS expressed high levels
      of the activation marker CD28 (P<0.05) and secreted both interferon-gamma (CD8:
      P<0.05) and interleukin-17 upon polyclonal mitogen or myelin oligodendrocyte
      glycoprotein antigen stimulation. However, T cells from patients with RRMS in
      remission, in contrast to relapse, had poor proliferative capacity (P<0.05)
      suggesting that they are controlled and kept in anergy. This anergy could be
      broken with CD28 stimulation that restored the T-cell replication. Furthermore,
      the patients with RRMS had normal levels of CD4(+) Foxp3(+) T regulatory cells
      but the frequency of Foxp3(+) cells lacking CD127 (interleukin-7 receptor) was
      lower in patients with MS (mean 12%) compared to healthy controls (mean 29%).
      Still, regulatory cells (CD25(+) sorted cells) from patients with RRMS displayed
      no difference in suppressive capacity. In conclusion, patients in
      relapse/remission demonstrate in vitro T-cell responses that are both Th1 and
      Th17 that, while in remission, appear to be controlled by tolerogenic mechanisms
      yet to be investigated.

PMID- 18624728
TI  - Activation-induced deaminase heterozygous MRL/lpr mice are delayed in the
      production of high-affinity pathogenic antibodies and in the development of lupus
      nephritis.
AB  - We previously reported that activation-induced deaminase (AID) heterozygous
      MRL/lpr mice have substantially lower levels of serum anti-dsDNA autoantibodies
      than AID wild-type littermates. Given the known functions of AID, here we
      examined whether this decrease in pathogenic autoantibodies in the heterozygotes
      was the result of a defect in class switch recombination, somatic hypermutation,
      or both. We report significant impairment of switch recombination to most
      isotypes except immunoglobulin G3 (IgG3) in vitro. However, serum levels of IgG
      were similar to AID wild-type levels even in very young mice. Mutation
      accumulation in the B cells from Peyer's patches also revealed reduced somatic
      hypermutation in the heterozygotes. Unlike the switch defect, the hypermutation
      defect probably resulted in an in vivo effect because the serum IgG antibodies
      from the heterozygotes were of strikingly lower affinity to dsDNA than serum IgG
      antibodies from wild-type littermates. This suggests that the somatic
      hypermutation defect resulted in impaired affinity maturation of autoantibodies
      in these mice and explains the low levels of specific anti-dsDNA antibodies in
      the heterozygotes. This correlated with a delay in the development of kidney
      damage. These results imply that AID levels impact the class switch recombination
      and somatic hypermutation mechanisms and directly implicate affinity maturation
      of autoantibodies in autoimmunity.

PMID- 18624729
TI  - Macrophage migration inhibitory factor stimulates interleukin-17 expression and
      production in lymph node cells.
AB  - Interleukin (IL)-17 is a pro-inflammatory cytokine produced by recently described
      T helper type 17 (Th17) cells, which have critical role in immunity to
      extracellular bacteria and the pathogenesis of several autoimmune disorders. IL-6
      and transforming growth factor (TGF)-beta are crucial for the generation of Th17
      cells in mice, while the production of IL-17 is supported by various cytokines,
      including IL-23, IL-1beta, IL-21, IL-15 and tumour necrosis factor (TNF)-alpha.
      In this study, the influence of a multifunctional cytokine, macrophage migration
      inhibitory factor (MIF), on IL-17 production in mice was investigated. Treatment
      of lymph node cells (LNCs) with recombinant MIF up-regulated mitogen-stimulated
      IL-17 expression and secretion. Additionally, LNCs from MIF knockout mice (mif(-/
      )) had severely impaired production of IL-17, as well as of IL-1beta, IL-6, IL-23
      and TGF-beta. When stimulated with recombinant IL-1beta, IL-23 or TNF-alpha,
      mitogen-triggered mif(-/-) LNCs were fully able to achieve the IL-17 production
      seen in wild-type (WT) LNCs, while the addition of IL-6 and TGF-beta had no
      effect. Finally, after injection of mice with complete Freund's adjuvant,
      secretion of IL-17 as well as the number of IL-17-positive cells was
      significantly lower in the draining lymph nodes of mif(-/-) mice in comparison
      with WT mice. The effect of MIF on IL-17 production was dependent on p38,
      extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and
      Janus kinase 2/signal transducer and activator of transcription 3 (Jak2/STAT3),
      and not on nuclear factor (NF)-kappaB and nuclear factor of activated T cells
      (NFAT) signalling. Bearing in mind the contribution of MIF and IL-17 to the
      pathology of inflammatory and autoimmune disorders, from the results presented
      here it seems plausible that targeting MIF biological activity could be a valid
      therapeutic approach for the treatment of such diseases.

PMID- 18624730
TI  - Suppression of cell proliferation and cytokine expression by HL-p36, a tick
      salivary gland-derived protein of Haemaphysalis longicornis.
AB  - Previously, a putative immunosuppressant-coding gene was identified from a
      complementary DNA library derived from the salivary glands of partially-fed
      Haemaphysalis longicornis. Using real-time polymerase chain reaction, the gene
      was shown to be predominantly expressed during blood feeding with the site of
      expression being mainly in the salivary glands; this was confirmed by Western
      blotting analysis. To investigate the function of this novel protein, in this
      study, we examined the proliferative responses of bovine mononuclear cells and
      murine splenic cells as well as the expression of profiles of several cytokines
      in these cells in the presence of the recombinant protein (H. longicornis-derived
      36 000 molecular weight protein: rHL-p36). The addition of rHL-p36 at the
      beginning of the 72 hr cultivation period clearly inhibited proliferation of
      several mitogen-stimulated cells in a dose-dependent manner, with concomitantly
      significant down-regulation of messenger RNA levels for interleukin-2. The
      inhibitory response could be abrogated by blockage of HL-p36 with antibody,
      suggesting the direct involvement of rHL-p36 in the cell proliferation.
      Furthermore, the proliferative response of splenocytes isolated from rHL-p36
      inoculated mice was significantly lower than for those from control mice,
      suggesting that rHL-p36 could also directly suppress immune responses in vivo.
      Interestingly, microarray analysis of the splenocytes showed that the expression
      of several immunomodulating genes was down-regulated by rHL-p36 inoculation. In
      conclusion, these results suggest that HL-p36 is an immunosuppressor that might
      play an important role in the modulation of host immune responses.

PMID- 18624731
TI  - CD8+ regulatory T cells are responsible for GAD-IgG gene-transferred tolerance
      induction in NOD mice.
AB  - Our previous studies demonstrated that lipopolysaccharide (LPS)-stimulated
      splenocytes, retrovirally transduced with a glutamate decarboxylate 65 (GAD) and
      immunoglobulin G (IgG) fusion construct, can protect non-obese diabetic (NOD)
      mice from diabetes by inducing GAD-specific tolerance, and also that there are
      increased numbers of CD4(+) regulatory T cells (Tregs) in GAD-IgG-treated NOD
      mice. However, little is known about the role of CD8(+) Tregs in GAD-IgG gene
      transferred tolerance induction in NOD mice. Here, we found that GAD-IgG
      transduced splenocytes induced an increase in the number of CD8(+) Foxp3(+) Tregs
      in vitro. Using a T-cell depletion assay, we found that, compared with undepleted
      groups, NOD recipients transfused with CD8(-) or CD8(-) CD25(-) GAD-IgG
      transduced splenocytes showed a decrease in the percentage of CD8(+) Foxp3(+) T
      cells, a high incidence of diabetes, serious insulitis, GAD-specific
      hyperresponsiveness at both the cellular and humoral levels, and changes in
      cytokine expression. These results indicate that CD8(+) Tregs, which were induced
      in vitro by GAD-IgG-transduced splenocytes, were also responsible for GAD-IgG
      gene-transferred tolerance induction in NOD mice.

PMID- 18624732
TI  - Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a
      possible immune escape mechanism of hepatitis B virus.
AB  - Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune
      response towards the virus. Myeloid dendritic cells (mDC) of patients with
      chronic HBV are impaired in their maturation and function, resulting in more
      tolerogenic rather than immunogenic responses, which may contribute to viral
      persistence. The mechanism responsible for altered mDC function remains unclear.
      The HBV-infected patients display large amounts of HBV particles and viral
      proteins in their circulation, especially the surface antigen HBsAg, which allows
      multiple interactions between the virus, its viral proteins and DC. To assess
      whether HBV directly influences mDC function, the effects of HBV and HBsAg on
      human mDC maturation and function were investigated in vitro. As already
      described for internalization of HBV by DC, the present study shows that
      peripheral blood-derived mDC of healthy controls also actively take up HBsAg in a
      time-dependent manner. Cytokine-induced maturation in the presence of HBV or
      HBsAg resulted in a significantly more tolerogenic mDC phenotype as demonstrated
      by a diminished up-regulation of costimulatory molecules and a decreased T-cell
      stimulatory capacity, as assessed by T-cell proliferation and interferon-gamma
      production. In addition, the presence of HBV significantly reduced interleukin-12
      production by mDC. These results show that both HBV particles and purified HBsAg
      have an immune modulatory capacity and may directly contribute to the dysfunction
      of mDC in patients with chronic HBV. The direct immune regulatory effect of HBV
      and circulating HBsAg particles on the function of DC can be considered as part
      of the mechanism by which HBV escapes immunity.

PMID- 18624734
TI  - An electronic thesaurus of Evidence Based Laboratory Medicine hematological and
      biochemical diagnostic tests.
AB  - The adoption of Evidence Based Laboratory Medicine (EBLM) has been hampered until
      today by the lack of effective tools. The SIMeL EBLM e-Thesaurus (on-line
      Repertoire of the diagnostic effectiveness of the laboratory, radiology and
      cardiology test) provides a useful support to clinical laboratory professionals
      and to clinicians for the interpretation of the diagnostic tests. The e-Thesaurus
      is an application developed using Microsoft Active Server Pages technology and
      carried out with Web Server Microsoft Internet Information Server and is
      available at the SIMeL website using a browser running JavaScript scripts
      (Internet Explorer is recommended). It contains a database (in Italian, English
      and Spanish) of the sensitivity and specificity (including the 95% confidence
      interval), the positive and negative likelihood ratios, the Diagnostic Odds Ratio
      and the Number Needed to Diagnose of more than 2000 diagnostic (most laboratory
      but also cardiology and radiology) tests. The e-Thesaurus improves the previous
      SIMeL paper and CD Thesaurus; its main features are a three languages search and
      a continuous and an easy updating capability.

PMID- 18624733
TI  - The mannose receptor binds Trichuris muris excretory/secretory proteins but is
      not essential for protective immunity.
AB  - Trichuris muris is a natural mouse model of the human gastrointestinal nematode
      parasite Trichuris trichiura and it is well established that a T helper type 2
      dominated immune response is required for worm expulsion. Macrophages accumulate
      in the large intestine of mice during infection and these cells are known to
      express the mannose receptor (MR), which may act as a pattern recognition
      receptor. The data presented here show for the first time that T. muris
      excretory/secretory products (E/S) induce bone-marrow-derived macrophages (BMDM)
      to produce several cytokines and have MR-binding activity. Using alternatively
      activated BMDM from MR knockout mice it is shown that the production of
      interleukin-6 partially depends on the MR. Infection of MR knockout mice with T.
      muris reveals that this receptor is not necessary for the expulsion of the
      parasite because MR knockout mice expel parasites with the same kinetics as wild
      type animals and have similar cytokine responses in the mesenteric lymph nodes.
      Furthermore, despite acting to reduce serum levels of proinflammatory mediators,
      absence of the MR does not lead to increased gut inflammation after T. muris
      infection when assessed by macrophage influx, goblet cell hyperplasia and crypt
      depth. This work suggests that, despite binding components of T. muris E/S, the
      MR is not critically involved in the generation of the immune response to this
      parasite.

PMID- 18624735
TI  - Topographical relationship between urethral rhabdosphincter and rectourethralis
      muscle: a better understanding of the apical dissection and the posterior
      stitches in radical prostatectomy.
AB  - OBJECTIVES: To clarify the topographical relationship between the urethral
      rhabdosphincter and the rectourethralis muscle as these structures lying dorsally
      to membranous urethra are important factors to post-prostatectomy urinary
      continence. METHODS: Pelvic floor specimens including prostate, bulbus penis, and
      anorectum, obtained from 15 male cadavers (ages at death 66 to 80 years), were
      examined with standard histologic and immunohistochemical techniques using
      semiserial sagittal and transverse sections. RESULTS: The rectourethralis muscle
      was defined. It was found to be located at the interface between the levator ani
      muscle and rectum. It was not possible to histologically identify the
      fibromuscular node known as the perineal body. The urethral rhabdosphincter was
      found to be inserted into the rectourethralis muscle, which is composed of the
      smooth muscle fibers. Abundant nerves passed between the rectourethralis muscle
      and the levator ani, or through the rectourethralis muscle. The urethral
      rhabdosphincter was closely attached to the apical or ventral portion of the
      rectourethralis muscle. Morphologically, the membranous urethra was fixed to the
      rectourethralis muscle through the urethral rhabdosphincter. CONCLUSIONS: The
      rectourethralis muscle influences the stabilization of membranous urethra. The
      posterior stitches for the reconstruction of the dorsal musculofascial plate
      might injure the nerve fibers running along and through the rectourethralis
      muscle.

PMID- 18624736
TI  - Longevity, early emergence and body size in a pollinating fig wasp--implications
      for stability in a fig-pollinator mutualism.
AB  - 1. Fig trees (Ficus) are pollinated only by agaonid wasps, whose larvae also gall
      fig ovules. Each ovule develops into either a seed (when pollinated) or a wasp
      (when an egg is also laid inside) but not both. 2. Ovipositing wasps
      (foundresses) favour ovules near the centre of the enclosed inflorescence
      (syconium or 'fig'), leaving ovules near the outer wall to develop into seeds.
      This spatial stratification of wasps and seeds ensures reproduction in both
      partners, and thereby enables mutualism persistence. However, the mechanism(s)
      responsible remain(s) unknown. 3. Theory shows that foundresses will search for
      increasingly rare inner ovules and ignore outer ovules, as long as ovipositing in
      outer ovules is sufficiently slow and/or if inner ovules confer greater fitness
      to wasps. The fig-pollinator mutualism can therefore be stabilized by strong time
      constraints on foundresses and by offspring fitness gradients over variation in
      ovule position. 4. Female fig wasps cannot leave their galls without male
      assistance. We found that females in outer ovules were unlikely to be released.
      Inner ovules thus have added value to foundresses, because their female offspring
      are more likely to mate and disperse. 5. For those offspring that did emerge,
      gall position (inner/outer) and body size did not influence the order in which
      female pollinators exited syconia, nor did early emerging wasps enjoy increased
      life spans. 6. We also found that the life spans of female wasps nearly doubled
      when given access to moisture. We suggest that conflict resolution in the fig
      pollinator mutualism may thus be influenced by tropical seasonality, because
      wasps may be less able to over-exploit ovules in dry periods due to time
      constraints.

PMID- 18624737
TI  - Maternal manipulation of hatching asynchrony limits sibling cannibalism in the
      predatory mite Phytoseiulus persimilis.
AB  - 1. Sibling cannibalism is a common phenomenon in the animal kingdom but entails a
      high risk of direct and inclusive fitness loss for the mother and her offspring.
      Therefore, mechanisms limiting sibling cannibalism are expected to be selected
      for. One way of maternal manipulation of sibling cannibalism is to influence
      hatching asynchrony between nearby laid eggs. This has rarely been tested
      experimentally. 2. We examined the ability of ovipositing females of the
      cannibalistic predatory mite Phytoseiulus persimilis to influence the occurrence
      of sibling cannibalism among offspring by manipulating hatching asynchrony of
      nearby laid eggs. 3. In the first experiment, we assessed the occurrence of
      sibling cannibalism in relation to the hatching interval (24 h and 48 h) between
      nearby laid eggs. In the second experiment, we tested whether ovipositing females
      discriminate sites containing young (24-h old) and old (48-h old) eggs, fresh and
      old traces (metabolic waste products and possibly pheromones) left by the same
      female (24 h and 48 h ago), or young eggs plus fresh female traces and old eggs
      plus old female traces. Both experiments were conducted with and without prey. 4.
      Without prey, siblings were more likely to cannibalize each other if the hatching
      interval between nearby laid eggs was short (24 h). Cannibalism occurred less
      often when senior siblings (protonymphs) experienced a delay in the opportunity
      to cannibalize junior siblings (larvae). 5. Independent of prey availability,
      females preferentially added new eggs to sites containing old eggs plus old
      female traces but did neither distinguish between young and old eggs presented
      without own traces nor between fresh and old traces presented without eggs. 6. We
      discuss cue perception and use by P. persimilis females and contrast the outcome
      of our experiments and theoretical predictions of sibling cannibalism. We
      conclude that P. persimilis mothers increase hatching asynchrony of nearby laid
      eggs to prevent sibling cannibalism on the last produced offspring. Such a
      behaviour may be considered a simple form of maternal care increasing the
      survival prospects of offspring.

PMID- 18624738
TI  - Niche differentiation depends on body size in a cichlid fish: a model system of a
      community structured according to size regularities.
AB  - 1. Communities of different species are often structured according to niche
      differentiation associated with competitive interactions. We show that similar
      principles may apply on an ecological time-scale when individuals of a species
      having a wide size variation compete for resources, using the Lake Tanganyika
      cichlid Lobochilotes labiatus (5-30 cm). This species has a mouth especially
      adapted to suck up invertebrates from rock crevices. 2. Individuals defended
      feeding territories against similar-sized conspecifics, but not against different
      sized ones. Thus, territories of similar-sized fish rarely overlapped, but up to
      a total of seven individuals (of seven size-ranks) had broadly overlapping
      territories with dissimilar-sized individuals. Comparison with expectation from
      the null model demonstrated clearly that observed size ratios between adjacent
      size rank were determined non-randomly regardless of sexual combinations. 3.
      Larger individuals took larger prey types of larger average size, but more
      importantly used wider rock crevices from which to suck food than smaller
      individuals. We calculated pairwise values of Schoener's index of diet overlap
      C(d) and the values of Levin's index of diet breadth B(d) (prey type and prey
      size) and the same for the width of the rock crevices used for foraging (C(r) and
      B(r)). C(d) remained high among all combinations of the seven ranks. In contrast,
      C(r) declined strongly in combinations of adjacent ranks (to 0.27), and was low
      or zero among further different size ranks. This shows that fish with overlapping
      territories divided the food resources largely through foraging site
      partitioning. Accordingly, B(d) did not depend on the size difference to the
      nearest two coinhabiting fish, whereas B(r) did. 4. We conclude that this L.
      labiatus community is structured non-randomly: body size-dependent effects on
      foraging site usage result in competition with, and territorial exclusion of,
      similar-sized individuals, but not of dissimilar-sized individuals that were
      accepted as coinhabitants. Accordingly, mean body size ratios (large/small)
      between two adjacent ranks were consistently approximately 1.28 [standard
      deviation (SD) = 0.07, n = 104], while approximately 1.34 from the null model (SD
      = 0.34, n = 10 400 simulations). We discuss our results as an example of
      Hutchinson's rule, applied originally to size ratios of different species.

PMID- 18624739
TI  - Recruitment and survival of immature seabirds in relation to oil spills and
      climate variability.
AB  - 1. In long-lived animals with delayed maturity, the non-breeding component of the
      population may play an important role in buffering the effects of stochastic
      mortality. Populations of colonial seabirds often consist of more than 50% non
      breeders, yet because they spend much of their early life at sea, we understand
      little about their impact on the demographic process. 2. Using multistate capture
      mark-recapture techniques, we analyse a long-term data set of individually
      identifiable common guillemots, Uria aalge Pont., to assess factors influencing
      their immature survival and two-stage recruitment process. 3. Analysis of the
      distribution of ringed common guillemots during the non-breeding season,
      separated by age classes, revealed that all age classes were potentially at risk
      from four major oil spills. However, the youngest age class (0-3 years) were far
      more widely spread than birds 4-6 years old, which were more widely spread than
      birds aged 6 and over. Therefore the chance of encountering an oil spill was age
      dependent. 4. A 2-year compound survival estimate for juvenile guillemots was
      weakly negatively correlated with winter sea-surface temperature, but was not
      influenced by oil spills. Non-breeder survival did not vary significantly over
      time. 5. In years following four oil spills, juvenile recruitment was almost
      double the value in non-oil-spill years. Recent work from Skomer Island showed a
      doubling of adult mortality associated with major oil spills, which probably
      reduced competition at the breeding colony, allowing increased immature
      recruitment to compensate for these losses. We discuss the implications of
      compensatory recruitment for assessing the impact of oil pollution incidents.

PMID- 18624740
TI  - An efficient multivariate approach for estimating preference when individual
      observations are dependent.
AB  - 1. We discuss aspects of resource selection based on observing a given vector of
      resource variables for different individuals at discrete time steps. A new
      technique for estimating preference of habitat characteristics, applicable when
      there are multiple individual observations, is proposed. 2. We first show how to
      estimate preference on the population and individual level when only a single
      site- or resource component is observed. A variance component model based on
      normal scores in used to estimate mean preference for the population as well as
      the heterogeneity among individuals defined by the intra-class correlation. 3.
      Next, a general technique is proposed for time series of observations of a vector
      with several components, correcting for the effect of correlations between these.
      The preference of each single component is analyzed under the assumption of
      arbitrarily complex selection of the other components. This approach is based on
      the theory for conditional distributions in the multi-normal model. 4. The method
      is demonstrated using a data set of radio-tagged dispersing juvenile goshawks and
      their site characteristics, and can be used as a general tool in resource or
      habitat selection analysis.

PMID- 18624741
TI  - Nonlinear impact of climate on survival in a migratory white stork population.
AB  - 1. There is growing evidence that ongoing climate change affects populations and
      species. Physiological limitation and phenotypic plasticity suggest nonlinear
      response of vital rates to climatic parameters, the intensity of environmental
      impact might be more pronounced while the frequency of extreme events increases.
      However, a poor understanding of these patterns presently hampers our predictive
      capabilities. 2. A recent climatic shift in the Sahel, from droughty to less
      severe condition, offers a good opportunity to test for an influence of the
      climatic regime on the response of organisms to their environment. Using a long
      term capture-mark-recapture data set on a white stork (Ciconia ciconia)
      population wintering in Sahel, we investigated potential change in the impact of
      environmental conditions on survival and recruitment probabilities between 1981
      and 2003. 3. We observed a decrease in the strength of the link between survival
      and Sahel rainfall during the last decade, down to a nondetectable level. Whether
      Sahel climate was found to affect the survival of storks under droughty
      conditions, individuals did not seem to respond to climatic variation when
      precipitation was more abundant. 4. This result gives evidence to a nonlinear
      response of a migrant bird to wintering environment. Present climate seems to
      fluctuate within a range of condition providing enough resources to maximize
      stork's survival. It suggests that whereas inter-annual variability impacted
      individuals, pluri-annual average condition affected the intensity of this
      impact. Such pattern may be more widespread than thought, and its modelling will
      be crucial to predict the impact of future climate change on population dynamics.

PMID- 18624742
TI  - Spatial variation in population growth rate and community structure affects local
      and regional dynamics.
AB  - 1. Theory predicting that populations with high maximum rates of increase
      (r(max)) will be less stable, and that metapopulations with high average r(max)
      will be less synchronous, was tested using a small protist, Bodo, that inhabits
      pitcher plant leaves (Sarracenia purpurea L.). The effects of predators and
      resources on these relationships were also determined. 2. Abundance data
      collected for a total of 60 populations of Bodo, over a period of 3 months, at
      six sites in three bogs in eastern Canada, were used to test these predictions.
      Mosquitoes were manipulated in half the leaves partway through the season to
      increase the range of predation rates. 3. Dynamics differed greatly among leaves
      and sites, but most populations exhibited one or more episodes of rapid increase
      followed by a population crash. Estimates of r(max) obtained using a linear mixed
      effects model, ranged from 1 x 5 to 2 x 7 per day. Resource levels (captured
      insect) and midge abundances affected r(max). 4. Higher r(max) was associated
      with greater temporal variability and lower synchrony as predicted. However, in
      contrast to expectations, populations with higher r(max) also had lower mean
      abundance and were more suppressed by predators. 5. This study demonstrates that
      the link between r(max) and temporal variability is key to understanding the
      dynamics of populations that spend little time near equilibrium, and to
      predicting and interpreting the effects of community structure on the dynamics of
      such populations.

PMID- 18624743
TI  - Effects of forage availability on growth and maturation  rates in water voles.
AB  - 1. In populations of small mammals, food supplementation typically results in
      higher population densities, body weights, growth rates and reproductive rates.
      However, few studies have demonstrated a relationship between forage levels and
      demographic rates in wild populations in the absence of supplementation. 2. We
      examined the association of levels of available forage with individual growth
      rates and time to sexual maturity in eight re-introduced and three naturally
      occurring populations of water voles (Arvicola terrestris). 3. Range sizes were
      smaller at sites with higher population densities. Mean forage availability and
      individual growth rates covaried with range size at each site. 4. The weight at
      which water voles became sexually mature was 112 g for females and 115 g for
      males and did not vary between study sites. Differences in growth rates therefore
      translated into differences in the time taken to reach maturity between sites. 5.
      In the re-introduced populations, mean days to maturity varied inversely with
      mean range length. Females took 7 days (18%, range 40-47 days) longer and males 5
      days (13%, range 40-45 days) longer to reach breeding condition at the sites with
      the shortest mean range lengths. 6. Evidence from this study suggests a possible
      mechanism by which increased population densities may reduce maturation rates in
      water voles through a reduction in mean range size, thereby limiting the
      availability of forage to each individual.

PMID- 18624744
TI  - Risk induced by a native top predator reduces alien mink movements.
AB  - 1. Nonlethal predation effects may have stronger impacts on prey populations than
      direct predation impacts, and this should also apply to intraguild predation. The
      consequences of such interactions become especially important if invasive, and
      potentially destructive alien predators act as intraguild prey. 2. We studied the
      predation-risk impacts of a re-colonizing native top predator, Haliaeetus
      albicilla (white-tailed sea eagle), on the movements of Mustela vison (American
      mink), an alien predator in Europe. We radiocollared 20 mink in two study areas
      in the outer archipelago of the Baltic Sea, South-west Finland, during 2004 and
      2005. In the archipelago, mink home ranges incorporate many islands, and mink are
      most predisposed to eagle predation while swimming between islands. Observed
      swimming distances of mink were compared to distances expected at random, and
      deviations from random swimming were explained by mink distance from nearest
      eagle nest, number of eagle observations near mink location, and mink home-range
      size. 3. Mink reduced their swimming distances with increasing sea eagle
      predation risk: for females, the reduction was 10% for an increase of 10 eagle
      observations, and 5% for each kilometre towards an eagle nest. Conclusions for
      males were restricted by their small sample size. 4. Our results suggest that
      female mink modify their behaviour according to eagle predation risk, which may
      reduce their population growth and have long-term cascading effects on lower
      trophic levels including bird, mammal and amphibian populations in the
      archipelago. Ecosystem restoration by bringing back the top predators may be one
      way of mitigating alien predator effects on native biota.

PMID- 18624745
TI  - Does the house mouse self-regulate its density in maturing sorghum and wheat
      crops?
AB  - 1. One of the central questions in population ecology and management is: what
      regulates population growth? House mouse Mus domesticus L. populations erupt
      occasionally in grain-growing regions in Australia. This study aimed to determine
      whether mouse populations are self-regulated in maturing sorghum and wheat crops.
      This was assessed by examining food supply to mice (i.e. yield) and the
      relationship between initial mouse density (D(I)) and density at harvest (D(H)).
      Eight levels of D(I) ranging from 89 to 5555 mice ha(-1) were introduced to
      sorghum at the hard dough stage and to wheat crops at the milky stage in mouse
      proofed pens. D(H) was measured by trapping out mice 49 days after the
      introduction. 2. There were at least 3.11 tonnes ha(-1) of wheat and 1.85 tonnes
      ha(-1) of sorghum grain available for mice at harvest. The estimated relationship
      between D(I) and D(H) was asymptotic exponential, with D(H) initially increasing
      almost linearly with D(I). When D(I) was above c. 500 mice ha(-1), D(H) increased
      asymptotically with D(I) and then saturated at c. 3100 mice ha(-1). The
      asymptotic increases in and saturation of D(H) was due partly to more young mice
      being born and recruited in pens treated with lower levels of D(I). 3. Our
      findings indicated that mouse densities in maturing cereal crops were driven by a
      numerical response of mice to the abundant supply of grain, modified by some
      unknown self-regulation mechanism that reduced this numerical response of mice at
      higher mouse densities. The mechanism was possibly spacing behaviours. Although
      the nature of this self-regulation mechanism is not known our model is,
      nevertheless, useful for predicting increases and eruptions in mouse population
      density in sorghum and wheat crops. Understanding the nature of this mechanism
      may provide insights into population processes that can be exploited in
      controlling mice in cereal crops.

PMID- 18624746
TI  - Prevalence and numbers of Salmonella spp. and Enterobacteriaceae on pork cuts in
      abattoirs in the Republic of Ireland.
AB  - AIMS: This study aimed to determine the numbers and types of Salmonella spp. and
      Enterobacteriaceae on pork cuts in the meat cutting room environment of four
      commercial pork abattoirs in the Republic of Ireland. METHODS AND RESULTS: Pork
      oysters (M. gluteus medius; n = 720) and swabs (n = 56) from equipment and
      surfaces were screened for Salmonella spp. using a DNA-based PCR method and
      confirmed by culture. Salmonella numbers were assessed using a three-tube most
      probable number (MPN) technique. Salmonella spp. was detected on 24/720 (3.3%)
      pork cuts (range of <0.03-0.36 MPN g(-1)) and in 7/56 (12.5%) environmental swabs
      (range of <0.03-1.10 MPN cm(-2)). There was significant variation in the
      prevalence of Salmonella on pork between different abattoirs and days of sampling
      (range of 0-31.7%). The predominant serotype was Salmonella serotype Typhimurium
      followed by Salmonella serotype Derby. CONCLUSIONS: Overall prevalence data
      conceal the key finding that there was considerable variation in the incidence of
      Salmonella on different days. A direct association between Salmonella
      contamination of pork cuts and equipment/surfaces was observed. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Prevalence and numbers of Salmonella were low; however,
      results clearly demonstrate the potential for cross-contamination from equipment
      and meat contact surfaces in the cutting room environment.

PMID- 18624747
TI  - Selective PCR detection of viable Enterobacter sakazakii cells utilizing
      propidium monoazide or ethidium bromide monoazide.
AB  - AIMS: The detection of viable Enterobacter sakazakii cells is important due to
      the association of this pathogen with outbreaks of life-threatening neonatal
      infections. The aim of this study was to optimize a PCR-based method for
      selective detection of only viable Ent. sakazakii cells in the presence of dead
      cells, utilizing propidium monoazide (PMA) or ethidium bromide monoazide (EMA).
      METHODS AND RESULTS: PMA or EMA was added to suspensions of viable and/or dead
      Ent. sakazakii cells at varying concentrations (10, 50 or 100 microg ml(-1))
      prior to DNA isolation and PCR with Ent. sakazakii-specific primers. At
      concentrations of 50 and 100 microg ml(-1), PMA completely inhibited PCR
      amplification from dead cells, while causing no significant inhibition of the
      amplification from viable cells. PMA was also effective in allowing selective PCR
      detection of only viable cells in mixtures of varying ratios of viable and dead
      cells. EMA was equally effective in preventing amplification from dead cells,
      however, it also inhibited DNA amplification from viable cells. CONCLUSIONS: This
      study demonstrated the efficiency of PMA for viable and dead differentiation of
      Ent. sakazakii, as well as the lack of selectivity of EMA for this purpose.
      SIGNIFICANCE AND IMPACT OF THE STUDY: PMA-PCR, in particular, will be useful for
      monitoring the resistance, survival strategies and stress responses of Ent.
      sakazakii in foods and the environment.

PMID- 18624749
TI  - Interleukin-6 and leptin as markers of energy metabolic changes in advanced
      ovarian cancer patients.
AB  - The progression of the neoplastic disease is characterized by specific
      alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea,
      anaemia, immunodepression and poor performance status (PS). The main cause of
      these symptoms and metabolic abnormalities is the chronic action of
      proinflammatory cytokines released both by tumour and immune cells. The present
      study aimed to assess the relationship between markers of inflammation (C
      Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic
      status (BMI, leptin, oxidative stress) according to clinical parameters in 104
      ovarian cancer patients at different stage and, moreover, to evaluate
      prospectively the changes of these parameters in accordance to tumour response in
      a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor
      PS were associated to high-grade inflammation and impaired energy metabolism.
      Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive
      factor of leptin, reactive oxygen species and glutathione peroxidase. In turn,
      leptin considered the key marker of the nutritional status and energy metabolism,
      was independently determined from stage and IL-6, not only from BMI. Moreover,
      the evaluation of the changes of these parameters during the course of the
      neoplastic disease in the subgroup of advanced ovarian cancer patients clearly
      unveils the central role of IL-6 and leptin as early markers of the metabolic
      alterations and symptoms associated to disease progression in advanced stage
      ovarian cancer. Their assessment should be included in monitoring disease
      outcome, especially when cancer is no longer curable and quality of life becomes
      the primary endpoint.

PMID- 18624750
TI  - GFP-tagged proteins visualized by freeze-fracture immuno-electron microscopy: a
      new tool in cellular and molecular medicine.
AB  - GFP-tagging is widely used as a molecular tool to localize and visualize the
      trafficking of proteins in cells but interpretation is frequently limited by the
      low resolution afforded by fluorescence light microscopy. Although complementary
      thin-section immunogold electron microscopic techniques go some way in aiding
      interpretation, major limitations, such as relatively poor structural
      preservation of membrane systems, low labelling efficiency and the two
      dimensional nature of the images, remain. Here we demonstrate that the electron
      microscopic technique freeze-fracture replica immunogold labelling overcomes
      these disadvantages and can be used to define, at high resolution, the precise
      location of GFP-tagged proteins in specific membrane systems and organelles of
      the cell. Moreover, this technique provides information on the location of the
      protein within the phospholipid bilayer, potentially providing insight into mis
      orientation of tagged proteins compared to their untagged counterparts.
      Complementary application of the freeze-fracture replica immunogold labelling
      technique alongside conventional fluorescence microscopy is seen as a novel and
      valuable approach to verification, clarification and extension of the data
      obtained using fluorescent-tagged proteins. The application of this approach is
      illustrated by new findings on PAT-family proteins tagged with GFP transfected
      into fibroblasts from patients with Niemann-Pick type C disease.

PMID- 18624751
TI  - Central chondrosarcoma progression is associated with pRb pathway alterations:
      CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro.
AB  - Chondrosarcomas are highly resistant to conventional radiation and chemotherapy,
      and surgical removal is the only option for curative treatment. Consequently,
      there is nothing to offer patients with inoperable tumours and metastatic
      disease. The aim of this study is to investigate genes involved in cell cycle
      control: CDK4, CDKN2A/p16, cyclin D1, p21, p53, MDM2 and c-MYC, which may point
      towards new therapeutic strategies. The pRb pathway was targeted using CDKN2A/p16
      overexpressing vectors and shRNA against CDK4 in chondrosarcoma cell lines
      OUMS27, SW1353, and CH2879. Cell survival and proliferation were assessed. CDK4,
      MDM2 and c-MYC expression levels were investigated by qPCR and
      immunohistochemistry (IHC) in 34 fresh frozen and 90 FFPE samples of enchondroma
      and chondrosarcoma patients. On a subset of 29 high-grade chondrosarcomas IHC for
      cyclin D1, p21 and p53 was performed. The overexpression of CDKN2A/p16 and
      knockdown of CDK4 by shRNA in OUMS27, SW1353 and CH2879 resulted in a significant
      decrease in cell viability and proliferation and a decreased ability to form
      colonies in vitro. Expression of CDK4 and MDM2 was associated with high-grade
      chondrosarcoma both at the mRNA and protein level. Combining these results with
      the expression of cyclin D1 and the previously shown loss of CDKN2A/p16
      expression show that the majority (96%; 28/29) of high-grade chondrosarcomas
      contain alterations in the pRb pathway. This suggests a role for the use of CDK4
      inhibitors as a treatment of metastatic or inoperable high-grade chondrosarcoma.

PMID- 18624753
TI  - Down-regulation of cardiac lineage protein (CLP-1)  expression in CLP-1 +/- mice
      affords.
AB  - In order to understand the transcriptional mechanism that underlies cell
      protection to stress, we evaluated the role of CLP-1, a known inhibitor of the
      transcription elongation complex (pTEFb), in CLP-1 +/- mice hearts. Using the
      isolated heart model, we observed that the CLP-1 +/- hearts, when subjected to
      ischaemic stress and evaluated by haemodynamic measurements, exhibit significant
      cardioprotection. CLP-1 remains associated with the pTEFb complex in the
      heterozygous hearts, where as it is released in the wild-type hearts suggesting
      the involvement of pTEFb regulation in cell protection. There was a decrease in
      Cdk7 and Cdk9 kinase activity and consequently in phosphorylation of serine-5 and
      serine-2 of Pol II CTD in CLP-1 +/- hearts. However, the levels of mitochondrial
      proteins, PGC-1alpha and HIF-1alpha, which enhance mitochondrial activity and are
      implicated in cell survival, were increased in CLP-1 +/- hearts subjected to
      ischaemic stress compared to that in wild-type CLP-1 +/- hearts treated
      identically. There was also an increase in the expression of pyruvate
      dehydrogenase kinase (PDK-1), which facilitates cell adaptation to hypoxic
      stress. Taken together, our data suggest that regulation of the CLP-1 levels is
      critical to cellular adaptation of the survival program that protects
      cardiomyocytes against stress due collectively to a decrease in RNA Pol II
      phosphorylation but an increase in expression of target proteins that regulate
      mitochondrial function and metabolic adaptation to stress.

PMID- 18624756
TI  - Surface morphology and mechanical properties of  fibroblasts from scleroderma
      patients.
AB  - Overproduction of extracellular matrix components by fibroblasts plays a key role
      in the pathogenesis of scleroderma. To investigate whether these functional
      alterations are accompanied by changes in the mechanical properties and
      morphology of fibroblast, atomic force microscopy was applied to dermal
      fibroblasts derived either from scleroderma patients or from healthy donors. No
      significant morphological differences could be observed among the different cell
      strains showing long cytoskeleton fibres similar in length and irregularly
      distributed protrusions on the cell surface. In contrast, significant differences
      in cellular stiffness of dermal fibroblasts derived from scleroderma lesions were
      detected. Compared to fibroblasts from healthy donors, diseased cells were
      characterized by a reduced elastic constant both when the global and local
      mechanical properties were probed. The altered stiffness of scleroderma
      fibroblasts may be important in the pathogenesis of the disease as it could lead
      to the abnormal response of fibroblasts to mechanical stimuli.

PMID- 18624757
TI  - microRNAs: tiny regulators of synapse function in development and disease.
AB  - The development and function of neuronal circuits within the brain are
      orchestrated by sophisticated gene regulatory mechanisms. Recently, microRNAs
      have emerged as a novel class of small RNAs that fine-tune protein synthesis.
      microRNAs are abundantly expressed in the vertebrate nervous system, where they
      contribute to the specification of neuronal cell identity. Moreover, microRNAs
      also play an important role in mature neurons. This review summarizes the current
      knowledge about the function of microRNAs in the nervous system with special
      emphasis on synapse formation and plasticity. The second part of this work will
      discuss the potential involvement of microRNAs in neurologic diseases. The study
      of brain microRNAs promises to expand our understanding of the mechanisms
      underlying higher cognitive functions and neurologic diseases.

PMID- 18624755
TI  - Neuronal cell death in neurodegenerative diseases: recurring themes around
      protein handling.
AB  - Neuronal cell death plays a role in many chronic neurodegenerative diseases with
      the loss of particular subsets of neurons. The loss of the neurons occurs during
      a period of many years, which can make the mode(s) of cell death and the
      initiating factors difficult to determine. In vitro and in vivo models have
      proved invaluable in this regard, yielding insight into cell death pathways. This
      review describes the main mechanisms of neuronal cell death, particularly
      apoptosis, necrosis, excitotoxicity and autophagic cell death, and their role in
      neurodegenerative diseases such as ischaemia, Alzheimer's, Parkinson's and
      Huntington's diseases. Crosstalk between these death mechanisms is also
      discussed. The link between cell death and protein mishandling, including
      misfolded proteins, impairment of protein degradation, protein aggregation is
      described and finally, some pro-survival strategies are discussed.

PMID- 18624759
TI  - Hypoxia response and microRNAs: no longer two separate worlds.
AB  - MicroRNAs (miRs) are short non-coding transcripts involved in a wide variety of
      cellular processes. Several recent studies have established a link between
      hypoxia, a well-documented component of the tumour microenvironment, and specific
      miRs. One member of this class, miR-210, was identified as hypoxia inducible in
      all the cell types tested, and is overexpressed in most cancer types. Its hypoxic
      induction is dependent on a functional hypoxia-inducible factor (HIF), thus
      extending the transcriptional repertoire of the latter beyond 'classic' genes.
      From a clinical standpoint, miR-210 overexpression has been associated with
      adverse prognosis in breast tumours and been detected in serum of lymphoma
      patients and could serve as a tool to define hypoxic malignancies. We discuss the
      role of miR-210 and its emerging targets, as well as possible future directions
      for clinical applications in oncology and ischaemic disorders.

PMID- 18624758
TI  - MicroRNA expression in lymphoid malignancies: new hope for diagnosis and therapy?
AB  - MicroRNAs are a newly discovered class of short (approximately 22 nt) naturally
      occurring single-stranded RNA molecules that regulate the expression of target
      genes post-transcriptionally. Despite only being discovered 7 years ago,
      microRNAs have been implicated as key regulatory molecules in nearly every
      biological process examined so far and abnormal expression of microRNAs have been
      linked to many forms of disease including cancer where they can function as both
      tumour-suppressors and oncogenes. So why are microRNAs causing so much
      excitement? And will this excitement translate into new medical breakthroughs?
      This review attempts to answer these questions in the wider context of cancer,
      focusing on the role that microRNAs play in normal lymphoid development and
      malignancy.

PMID- 18624760
TI  - Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous
      squamous cell carcinoma cell line SCL-1.
AB  - Skin cancers are by far the most common human malignancies. Retinoids have shown
      promising preventive and therapeutic effects against a variety of human
      malignancies. The aim of this study was to investigate the apoptosis-inducing
      effect of acitretin on human skin squamous cell carcinoma (SCC) SCL-1 cells. We
      found that acitretin preferentially inhibited the growth of SCL-1 cells in a dose
      and time-dependent manner, but not of non-malignant keratinocyte HaCaT cells.
      This inhibition appeared to be due to induction of apoptosis as revealed by
      enzyme-linked immunosorbent assay. AnnexinV/propidium iodide assay and
      morphological observation confirmed the pro-apoptotic effect of acitretin on SCL
      1 cells. We further demonstrated that apoptosis was induced within 1-2 days and
      involved activation of caspases-8, -9, -3 and poly (ADP-ribose) polymerase
      (PARP). Caspase-8 inhibitor effectively suppressed acitretin-induced apoptosis
      whereas caspase-9 inhibitor did not. Acitretin increased the levels of CD95
      (Fas), CD95-ligand and Fas-associated death domain. Neutralizing ZB4 anti-Fas
      antibody significantly inhibited the apoptosis in SCL-1 cells induced by
      acitretin. These results suggest that acitretin is able to induce apoptosis in
      skin cancer cells possibly via death receptor CD95 apoptosis pathway without
      affecting the viability of normal keratinocyte.

PMID- 18624762
TI  - The immune reaction against allogeneic necrotic cells is reduced in Annexin A5
      knock out mice whose macrophages display an anti-inflammatory phenotype.
AB  - Proteins of the annexin family bind to phospholipids in a Ca(2+) dependent
      manner. The exposure of phosphatidylserine (PS) by apoptotic as well as necrotic
      cells is one major eat-me-signal for macrophages. Annexin A5 (Anx A5)
      preferentially binds to PS. The availability of Anx A5 knock out (KO) mice
      allowed us to investigate for the first time if endogenous Anx A5 modulates the
      immune response towards allogeneic cells. Furthermore, the effect of Anx A5 gene
      deletion on the phagocytic process as well as on the inflammatory reaction of
      macrophages was explored. We found that Anx A5 KO mice have a strongly reduced
      allogeneic cellular immune reaction against primary as well as secondary necrotic
      cells. In vivo phagocytosis experiments revealed that macrophages of Anx A5 KO
      mice displayed an increased uptake of necrotic cells. Additionally, an increased
      secretion of the anti-inflammatory cytokine IL-10 of isolated macrophages of Anx
      A5 KO mice after contact with necrotic cells was observed. Furthermore, the
      promoter activity of the Anx A5 gene was enhanced after stimulation of
      macrophages. The tumour size of an allogeneic tumour regressed faster when
      endogenous Anx A5 was present. These data demonstrate that endogenous Anx A5
      influences the phagocytosis of necrotic cells, modulates the immune response
      towards allogeneic cells and acts as an inflammatory protein.

PMID- 18624763
TI  - Lysophosphatidylcholine up-regulates human endothelial nitric oxide synthase gene
      transactivity by c-Jun N-terminal kinase signalling pathway.
AB  - Human endothelial nitric oxide synthase (eNOS) plays a pivotal role in
      maintaining blood pressure homeostasis and vascular integrity. It has recently
      been reported that mitogen-activated protein kinases (MAPKs) are intimately
      implicated in expression of eNOS. However detailed mechanism mediated by them
      remains to be clarified. In this study, eNOS gene transactivity in human
      umbilical vein endothelial cells was up-regulated by stimulation of
      lysophosphatidylcholine (LPC). The stimulation of LPC highly activated both
      extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase
      (JNK), with differences in the dynamic processes of activation between them.
      Unexpectedly, p38 MAPK could not be activated by the stimulation of LPC. The
      activation of JNK signalling pathway by overexpression of JNK or its upstream
      kinase active mutant up-regulated the transactivity of eNOS significantly, but
      the activation of p38 signalling pathway down-regulated it largely. The
      inhibition of either ERK1/2 or JNK signalling pathway by kinase-selective
      inhibitors could markedly block the induction of the transactivity by LPC. It was
      observed by electrophoretic mobility shift assay that LPC stimulated both SP1 and
      AP1 DNA binding activity to go up. Additionally using decoy oligonucleotides
      proved that SP1 was necessary for maintaining the basal or stimulated
      transactivity, whereas AP1 contributed mainly to the increase of the stimulated
      transactivity. These findings indicate that the up-regulation of the eNOS gene
      transactivity by LPC involves the enhancement of SP1 transcription factor by the
      activation of JNK and ERK1/2 signalling pathways and AP1 transcription factor by
      the activation of JNK signalling pathway.

PMID- 18624766
TI  - A molecular study of pathways involved in the inhibition of cell proliferation in
      neuroblastoma B65 cells by the GSK-3 inhibitors lithium and SB-415286.
AB  - Pharmacological GSK-3 inhibitors are potential drugs for the treatment of
      neurodegenerative diseases, cancer and diabetes. We examined the
      antiproliferative effects of two GSK-3 inhibitors, lithium and SB-415286, on B65
      neuroblastoma cell line. Treatment of B65 cells with either drug administered
      separately caused a decrease in cell proliferation that was associated with
      G(2)/M cell cycle arrest. Cell-cycle proteins such as cyclins D, E, A, cdk4 and
      cdk2 were up-regulated. Since lithium and SB-415286-induced G(2)/M arrest we
      studied changes in the expression of proteins involved in this phase,
      specifically cyclin B, cdc2 and the phosphorylated form of this protein (tyr15
      cdc2). Both drugs increased the expression of tyr15-cdc2, thus inhibiting
      mitosis. On the other hand, SB-415286 increased the expression of SIRT2, involved
      in the regulation of proliferation. Moreover, cell-cycle arrest mediated by SB
      415286 was accompanied by apoptosis that was not prevented by 100 microM of zVAD
      fmk (benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone), a pan-caspase inhibitor.
      Likewise, GSK-3 inhibitors did not affect the mitochondrial release of apoptosis
      inducing factor (AIF). We conclude that inhibitors of GSK-3 induced cell-cycle
      arrest, mediated by the phosphorylation of cdc2 and, in the case of SB-415286,
      SIRT2 expression, which induced apoptosis in a caspase-independent manner.

PMID- 18624767
TI  - Acute heart inflammation: ultrastructural and functional aspects of macrophages
      elicited by Trypanosoma cruzi infection.
AB  - The heart is the main target organ of the parasite Trypanosoma cruzi, the causal
      agent of Chagas' disease, a significant public health issue and still a major
      cause of morbidity and mortality in Latin America. During the acute disease,
      tissue damage in the heart is related to the intense myocardium parasitism. To
      control parasite multiplication, cells of the monocytic lineage are highly
      mobilized. In response to inflammatory and immune stimulation, an intense
      migration and extravasation of monocytes occurs from the bloodstream into heart.
      Monocyte differentiation leads to the formation of tissue phagocytosing
      macrophages, which are strongly activated and direct host defence. Newly elicited
      monocyte-derived macrophages both undergo profound physiological changes and
      display morphological heterogeneity that greatly differs from originally non
      inflammatory macrophages, and underlie their functional activities as potent
      inflammatory cells. Thus, activated macrophages play a critical role in the
      outcome of parasite infection. This review covers functional and ultrastructural
      aspects of heart inflammatory macrophages triggered by the acute Chagas' disease,
      including recent discoveries on morphologically distinct, inflammation-related
      organelles, termed lipid bodies, which are actively formed in vivo within
      macrophages in response to T. cruzi infection. These findings are defining a
      broader role for lipid bodies as key markers of macrophage activation during
      innate immune responses to infectious diseases and attractive targets for novel
      anti-inflammatory therapies. Modulation of macrophage activation may be central
      in providing therapeutic benefits for Chagas' disease control.

PMID- 18624769
TI  - The ongoing microRNA revolution and its impact in biology and medicine.

PMID- 18624768
TI  - MicroRNAs and prostate cancer.
AB  - Prostate cancer (CaP) is the most frequently diagnosed malignant tumour and the
      second leading cause of cancer deaths in American men. One of the most troubling
      aspects of this disease is that, after androgen ablation therapy, androgen
      dependent cancer cells inevitably progress to an androgen-independent status, for
      which no effective treatment has yet been developed. To date, the mechanisms that
      underlie the occurrence and progression of CaP remain largely unknown. Recent
      studies suggest that microRNAs (miRNAs) are involved in human tumourigenesis.
      Some aberrantly expressed miRNAs have been discovered in CaP cell lines,
      xenografts and clinical tissues and these CaP-related miRNAs may play critical
      roles in the pathogenesis of CaP. This review provides an overview of current
      findings about aberrantly expressed miRNAs in CaP. Although a number of CaP
      related miRNAs were discovered, to date, only five are characterized for their
      functionalities: three as oncogenes and two as tumour suppressors. To understand
      the mechanisms of miRNA action as oncogenes or tumour suppressors, mRNA targets
      of miRNAs were characterized. Oncogenic miRNAs down-regulate the expression of
      apoptosis-related genes, and tumour suppressor miRNAs target the proliferation
      related genes. Importantly, there is evidence that CaP-related miRNAs are
      regulated through androgen signalling and that this regulation may contribute to
      the development of androgen independence. Due to the oncogenic or tumour
      suppressive properties of CaP-related miRNAs, they are highly likely to be of
      clinical use first as biomarkers but more importantly as therapeutic targets for
      prostate cancer treatment in the near future.

PMID- 18624770
TI  - In vivo engineering of a human vasculature for bone tissue engineering
      applications.
AB  - The neovascularization of three-dimensional voluminous tissues, such as bone,
      represents an important challenge in tissue engineering applications. The
      formation of a preformed vascular plexus could maintain cell viability and
      promote vascularization after transplantation. We have developed a three
      dimensional spheroidal coculture system consisting of human primary endothelial
      cells and human primary osteoblasts (hOBs) to improve angiogenesis in bone tissue
      engineering applications. In this study, we investigated the survival and
      vascularization of the engineered implants in vivo. Endothelial cell spheroids
      were cocultured with hOBs in fibrin and seeded into scaffolds consisting of
      processed bovine cancellous bone (PBCB). The cell-seeded scaffolds were evaluated
      for their angiogenic potential in two different in vivo assays: the chick embryo
      chorioallantoic membrane (CAM) model and the severe combined immunodeficiency
      disorder (SCID) mouse model. In both assays, the development of a complex three
      dimensional network of perfused human neovessels could be detected. After
      subcutaneous implantation into immunodeficient mice, the newly formed human
      vasculature was stabilized by the recruitment of murine smooth muscle alpha-actin
      positive mural cells and anastomoses with the mouse vasculature. We conclude that
      this endothelial cell spheroid system can be used to create a network of
      functional perfused blood vessels in vivo. The finding that this process takes
      place with high efficacy in the presence of co-implanted primary osteoblasts and
      in an osteoconductive environment provided by the PBCB scaffold, suggests that
      this system may be suitable for improving vascularization in bone tissue
      engineering.

PMID- 18624771
TI  - Cysteinylation and homocysteinylation of plasma protein thiols during ageing of
      healthy human beings.
AB  - The purpose of the present study was to determine the relative amount of S
      thiolated proteins (i.e. S-homocysteinylated, S-cysteinylglycinylated, S
      glutathionylated and S-cysteinylated proteins) to the total protein thiols (i.e.
      the sum of reduced protein sulphydryl groups (PSHs) and protein mixed disulphides
      with homocysteine [HcySH], cysteinylglycine, cysteine [CysSH] and glutathione) in
      the plasma of healthy individuals aged 20 to 93. After plasma separation, total
      protein thiols, S-thiolated proteins, as well as CysSH, cystine, HcySH and
      homocystine were measured by high-performance liquid chromatography (HPLC) with
      fluorescence determination of the thiol-monobromobimane conjugate. Determination
      of plasma levels of protein thiols was performed by spectrophotometry with 5,5'
      dithiobis(2-nitrobenzoic acid) as a titrating agent. The present study
      demonstrates an age-dependent reduction in the amount of PSHs, and an age
      dependent increase in cysteinylated and homocysteinylated plasma proteins in
      healthy human beings. This indicates that the efficiency of the reduced protein
      thiol pool as an antioxidant defence system decreases with age, possibly causing
      an increased risk of irreversible oxidation (i.e. further oxidation to sulphinic
      and sulphonic acids, which are usually not reducible by thiol reducing agents) of
      sulphydryl groups of plasma proteins. The drop in the plasma level of protein
      sulphydryl groups suggests depletion and/or impairment of the antioxidant
      capacity of plasma, likely related to an alteration of the delicate balance
      between the different redox forms of thiols.

PMID- 18624773
TI  - A pro-inflammatory signature mediates  FGF2-induced angiogenesis.
AB  - Fibroblast growth factor-2 (FGF2) is a potent angiogenic growth factor. Here,
      gene expression profiling of FGF2-stimulated microvascular endothelial cells
      revealed, together with a prominent pro-angiogenic profile, a pro-inflammatory
      signature characterized by the upregulation of pro-inflammatory
      cytokine/chemokines and their receptors, endothelial cell adhesion molecules and
      members of the eicosanoid pathway. Real-time quantitative PCR demonstrated early
      induction of most of the FGF2-induced, inflammation-related genes. Accordingly,
      chick embryo chorioallantoic membrane (CAM) and murine Matrigel plug angiogenesis
      assays demonstrated a significant monocyte/macrophage infiltrate in the areas of
      FGF2-driven neovascularization. Similar results were obtained when the
      conditioned medium (CM) of FGF2-stimulated endothelial cells was delivered onto
      the CAM, suggesting that FGF2-upregulated chemoattractants mediate the
      inflammatory response. Importantly, FGF2-triggered new blood vessel formation was
      significantly reduced in phosphatidylinositol 3-kinase-gamma null mice exhibiting
      defective leucocyte migration or in clodronate liposome-treated, macrophage
      depleted mice. Furthermore, the viral pan-chemokine antagonist M3 inhibited the
      angiogenic and inflammatory responses induced by the CM of FGF2-stimulated
      endothelial cells and impaired FGF2-driven neovascularization in the CAM assay.
      These findings point to inflammatory chemokines as early mediators of FGF2-driven
      angiogenesis and indicate a non-redundant role for inflammatory cells in the
      neovascularization process elicited by the growth factor.

PMID- 18624772
TI  - Activation of protease calpain by oxidized and glycated LDL increases the
      degradation of endothelial nitric oxide synthase.
AB  - Oxidation and glycation of low-density lipoprotein (LDL) promote vascular injury
      in diabetes; however, the mechanisms underlying this effect remain poorly
      defined. The present study was conducted to determine the effects of 'heavily
      oxidized' glycated LDL (HOG-LDL) on endothelial nitric oxide synthase (eNOS)
      function. Exposure of bovine aortic endothelial cells with HOG-LDL reduced eNOS
      protein levels in a concentration- and time-dependent manner, without altering
      eNOS mRNA levels. Reduced eNOS protein levels were accompanied by an increase in
      intracellular Ca(2+), augmented production of reactive oxygen species (ROS) and
      induction of Ca(2+)-dependent calpain activity. Neither eNOS reduction nor any of
      these other effects were observed in cells exposed to native LDL. Reduction of
      intracellular Ca(2+) levels abolished eNOS reduction by HOG-LDL, as did
      pharmacological or genetic through calcium channel blockers or calcium chelator
      BAPTA or inhibition of NAD(P)H oxidase (with apocynin) or inhibition of calpain
      (calpain 1-specific siRNA). Consistent with these results, HOG-LDL impaired
      acetylcholine-induced endothelium-dependent vasorelaxation of isolated mouse
      aortas, and pharmacological inhibition of calpain prevented this effect. HOG-LDL
      may impair endothelial function by inducing calpain-mediated eNOS degradation in
      a ROS- and Ca(2+)-dependent manner.

PMID- 18624774
TI  - Paraoxonase 1 activities and polymorphisms in autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) comprise a complex and heterogeneous group of
      conditions of unknown aetiology, characterized by significant disturbances in
      social, communicative and behavioural functioning. Recent studies suggested a
      possible implication of the high-density lipoprotein associated
      esterase/lactonase paraoxonase 1 (PON1) in ASD. In the present study, we aimed at
      investigating the PON1 status in a group of 50 children with ASD as compared to
      healthy age and sex matched control participants. We evaluated PON1
      bioavailability (i.e. arylesterase activity) and catalytic activity (i.e.
      paraoxonase activity) in plasma using spectrophotometric methods and the two
      common polymorphisms in the PON1 coding region (Q192R, L55M) by employing Light
      Cycler real-time PCR. We found that both PON1 arylesterase and PON1 paraoxonase
      activities were decreased in autistic patients (respectively, P < 0.001, P <
      0.05), but no association with less active variants of the PON1 gene was found.
      The PON1 phenotype, inferred from the two-dimensional enzyme analysis, had a
      similar distribution in the ASD group and the control group. In conclusion, both
      the bioavailability and the catalytic activity of PON1 are impaired in ASD,
      despite no association with the Q192R and L55M polymorphisms in the PON1 gene and
      a normal distribution of the PON1 phenotype.

PMID- 18624775
TI  - Assessment of embryonic myocardial cell differentiation using a dual fluorescent
      reporter system.
AB  - Recent studies have identified the existence of undifferentiated myocardial cells
      during early embryonic as well as post-natal stages of heart development. While
      primitive cells present in the precardiac mesoderm can differentiate into
      multiple cell types of the cardiovascular system, the developmental potential of
      undifferentiated cells identified in the ventricular myocardium after chamber
      formation is not well characterized. A deeper understanding of mechanisms
      regulating myocardial cell differentiation will provide further insights into the
      normal and pathological aspects of heart development. Here, we showed that Nkx2.5
      positive and sarcomeric myosin negative cells were predominantly localized in the
      right ventricular myocardium of CD1 mice at E11.5 stage. We confirmed that
      myocardial regions negative for saromeric myosin were also devoid of atrial
      natriuretic factor (ANF). These observations are consistent with our previous
      study, which showed that ANF expression is restricted to moderately
      differentiated and mature myocardial cells in E11.5 myocardium of C3H/FeJ mice.
      Further, we found that the receptor c-Kit, a marker for early embryonic
      myocardial progenitor cells, is not expressed in the undifferentiated cells of
      the E11.5 myocardium. To monitor the differentiation potential of Nkx2.5(+)/ANF(
      ) cells in vitro, we developed a novel double fluorescent reporter system.
      Subsequently, we confirmed that the majority of Nkx2.5(+)/ANF(-) cells expressed
      mature myocyte markers such as sarcomeric myosin, MLC2V and alpha-cardiac actin
      after 48 hrs in culture, albeit at lower levels compared to Nkx2.5(+)/ANF(+) or
      Nkx2.5(-)/ANF(+) cell populations. Our results suggest that fluorescent reporters
      under the control of lineage-specific promoters can be used to study myocardial
      cell differentiation in response to various exogenous or pharmacological agents.

PMID- 18624776
TI  - IL-12 immunotherapy of murine leukaemia:  comparison of systemic versus gene
      modified cell therapy.
AB  - The ability of IL-12 to initiate anti-leukaemia immune responses has been well
      established; however clinical outcomes fail to recapitulate the therapeutic
      benefits observed in the laboratory. To address this, we compared two systems of
      IL-12 therapy that elicit protective immune responses against the murine acute
      lymphoblastic leukaemia (ALL) cell line, 70Z/3. These systems differ in the
      method of IL-12 administration and ultimately result in leukaemia clearance by
      distinct mechanisms, emphasizing the importance of treatment vehicle. Injecting
      low-dose IL-12 was sufficient to elicit long-term protective immunity against an
      established leukaemia burden, mediated by both CD4(+) and CD8(+) T cells. These
      findings agree with the standard model of IL-12 activity. We compared this
      protocol to a cell-based approach in which a novel lentiviral vector (LV)
      expressing murine IL-12 was created, 70Z/3 cells transduced, and clones selected
      that stably secrete different amounts of IL-12. We found that only a small
      proportion (1%) of IL-12 secreting cells were required for rejection but that the
      amount of IL-12 produced per cell was critical for successful therapy.
      Importantly, the levels of IL-12 required were found to be higher than the levels
      reported to date in the human clinical trial literature. We found that the cell
      based approach led to protective immunity that was both long-term and specific
      but dependent primarily on a CD4(+) cellular subset alone. Our results highlight
      that the mode of IL-12 delivery has a distinct impact on the immune response
      initiated, leading to leukaemia clearance by disparate mechanisms. We also
      establish a new and critical parameter, IL-12 production/cell, which may have
      significant implications for future therapeutic design.

PMID- 18624778
TI  - Evaluation of blood vessel ingrowth in fibrin gel subject to type and
      concentration of growth factors.
AB  - Our aim was to quantitatively assess the angiogenetic effects of VEGF and bFGF
      immobilized in a fibrin-based drug delivery system in a suitable subcutaneous rat
      model. After evaluation of a suitable implantation technique (6 rats), four
      teflon isolation chambers containing fibrin gel matrices were implanted
      subcutaneously in an upside-down fashion on the back of 30 Lewis rats. The
      matrices consisted of 500 microl fibrin gel with two different fibrinogen
      concentrations (10 mg/ml or 40 mg/ml fibrinogen) and 2 I.U./ml thrombin and
      contained VEGF and bFGF in five different concentrations (0 to 250 ng/ml each).
      At 3, 7 and 14 days after implantation, matrices were explanted and subjected to
      histological and morphometrical analysis. At 1 week, the volume of the fibrin
      clots was significantly smaller in the 100 and 250 ng/ml VEGF and bFGF groups in
      comparison to lower concentrated growth factors. At 1 and 2 weeks, the use of
      growth factors in low concentrations (25 ng/ml VEGF and bFGF) significantly
      increased the amount of fibrovascular tissue, average fraction of blood vessels
      and number of blood vessels at the matrix-host interface in comparison to growth
      factor-free controls. Higher concentrations were neither associated with further
      increase of tissue formation nor with increased sprouting of blood vessels in
      this model. This study demonstrates that fibrin gel-immobilized angioinductive
      growth factors efficiently stimulate generation of fibrovascular tissue and
      sprouting of blood vessels in a newly developed subcutaneous upside-down
      isolation chamber model with an optimum between 25 and 100 ng/ml.

PMID- 18624779
TI  - A systematic review of informal caregivers' needs in providing home-based end-of
      life care to people with cancer.
AB  - AIMS: This paper presents the results of a systematic review examining the
      practical information needs of informal caregivers providing home-based
      palliative and end-of-life care to people with advanced cancer. BACKGROUND:
      Modern hospice care has led to increases in home-based palliative care services,
      with informal caregivers assuming responsibility for the majority of care. In
      response, health policy emphasises the provision of palliative care services in
      which both the patient and carer receive adequate support throughout illness and
      death. While the emotional needs of carers have been extensively researched,
      their practical needs with respect to the provision of physical care are yet to
      receive systematic attention. DESIGN: Systematic review. METHODS: Eligible
      articles were identified via electronic searches of research and evidence-based
      databases, hand-searching of academic journals and searches of non-academic grey
      literature websites. Quality of research was assessed via accepted guidelines for
      reviewing non-randomised, observational and qualitative literature. Data were
      synthesised by comparing and contrasting the findings to identify prominent
      themes. RESULTS: Research consistently highlights this lack of practical support,
      often related to inadequate information exchange. These deficits typically
      manifest in relatives adopting a 'trial and error' approach to palliative care.
      Informal carers request a greater quantity of practically-focussed information,
      improvements in quality and increased methods of dissemination. CONCLUSION:
      Synthesis of the literature suggests that home-based palliative care services
      have been insufficiently focussed on assisting informal caregivers acquire
      practical nursing skills. RELEVANCE TO CLINICAL PRACTICE: Enhanced access to
      professional advice represents a potentially effective method of increasing
      carers' confidence in their ability to undertake practical aspects of home-based
      care. Evidence suggests that nurses and other health providers may better assist
      home-based carers by providing the information and skills-training necessary to
      facilitate this. This may necessitate the involvement of carers in the design and
      testing of new educational interventions.

PMID- 18624777
TI  - Parenchymal and vascular Abeta-deposition and its effects on the degeneration of
      neurons and cognition in Alzheimer's disease.
AB  - The deposition of the amyloid beta-protein (Abeta) is one of the pathological
      hallmarks of Alzheimer's disease (AD). Abeta-deposits show the morphology of
      senile plaques and cerebral amyloid angiopathy (CAA). Senile plaques and vascular
      Abeta-deposits occur first in neocorti-cal areas. Then, they expand
      hierarchically into further brain regions. The distribution of Abeta plaques
      throughout the entire brain, thereby correlates with the clinical status of the
      patients. Imaging techniques for Abeta make use of the hierarchical distribution
      of Abeta to distinguish AD patients from non-AD patients. However, pathology seen
      in AD patients represents a late stage of a pathological process starting 10-30
      years earlier in cognitively normal individuals. In addition to the fibrillar
      amyloid of senile plaques, oligomeric and monomeric Abeta is found in the brain.
      Recent studies revealed that oligomeric Abeta is presumably the most toxic Abeta
      aggregate, which interacts with glutamatergic synapses. In doing so, dendrites
      are presumed to be the primary target for Abeta-toxicity. In addition, vascular
      Abeta-deposits can lead to capillary occlusion and blood flow disturbances
      presumably contributing to the alteration of neurons in addition to the direct
      neurotoxic effects of Abeta. All these findings point to an important role of
      Abeta and its aggregates in the neurodegenerative process of AD. Since there is
      already significant neuron loss in AD patients, treatment strategies aimed at
      reducing the amyloid load will presumably not cure the symptoms of dementia but
      they may stop disease progression. Therefore, it seems to be necessary to protect
      the brain from Abeta-toxicity already in stages of the disease with minor neuron
      loss before the onset of cognitive symptoms.

PMID- 18624780
TI  - Evaluating effects of a prenatal breastfeeding education programme on women with
      caesarean delivery in Taiwan.
AB  - AIMS: The aims of this study were: (1) to evaluate the effectiveness of a
      prenatal breastfeeding education programme for primigravida women who have
      elected caesarean section as a model of delivery and (2) to evaluate its
      effectiveness for encouraging a positive attitude to breastfeeding and rooming-in
      and to increase exclusive breastfeeding rates within hospital and at one month
      postpartum. BACKGROUND: Prenatal preparation for pregnant women about
      breastfeeding enhances their practical knowledge and skills about breastfeeding
      techniques, which prepares them when encountering possible difficulties. DESIGN:
      A quasi-experimental design was used. METHODS: The targeted population was
      primigravidas at 36-39 weeks and who had chosen to deliver by caesarean section.
      The study consisted of approximately 100 individuals; the control group consisted
      of 46 subjects and the following 54 made up the experimental group. The study was
      conducted at a hospital in Taiwan. RESULTS: The results of the study show that
      the subjects of the experimental group exhibited a more positive breastfeeding
      attitude (88.9 vs. 79.8, t = 7.40, p < 0.001), a higher 24 hours rooming-in rate
      (87% vs. 63%, chi(2) = 16.06, p < 0.001) and a higher exclusive breastfeeding
      rate (79.6% vs. 52.2%, chi(2) = 8.38, p = 0.004) during hospital stays and a
      higher exclusive breastfeeding rate (75.9% vs. 34.7%, chi(2) = 16.98, p < 0.001)
      for the one month postpartum period. CONCLUSION: Results suggest that providing
      education booklets, videos and telephone interview on breastfeeding prior to a
      caesarean delivery may contribute to breastfeeding attitude and improved rooming
      in and exclusive breastfeeding rates. RELEVANCE TO CLINICAL PRACTICE: This
      breastfeeding education programme has proven to be successful in aiding women
      breastfeeding after a caesarean delivery and provides health care professionals
      with an evidence-based intervention.

PMID- 18624781
TI  - Nursing practice and oral fluid intake of older people with dementia.
AB  - AIM: This paper describes the findings of a descriptive study about what nurses
      do to ensure that older people with dementia have adequate hydration. BACKGROUND:
      Frail nursing home residents, particularly those who cannot accurately
      communicate their thirst as a result of Alzheimer's disease and who depend on
      nursing staff for their fluid intake, are at risk of dehydration. While the
      interventions that promote nutrition in older people with dementia are
      documented, the specific interventions for improving oral hydration in older
      people with dementia remain poorly studied and understood. DESIGN: Observational
      study. METHODS: Ten care workers and seven residents were observed for the types
      of behavioural nursing interventions and assistance provided to residents when
      promoting oral fluid intake. Observational data were compared with resident-care
      plans to determine whether what was carried out by care workers was consistent
      with what was being documented. RESULTS: Care workers provided a wide variety of
      behavioural interventions to the residents when promoting oral fluid intake. The
      resident-care plans did not sufficiently represent the specific interventions
      implemented by care workers. CONCLUSIONS: A more rigorous approach is required in
      defining the specific behavioural interactions practised by care workers, which
      promote oral fluid intake in older people with dementia. Nurses determined the
      content of care documented in care plans, yet they were not the predominant
      implementers of that care. Care plans need to be accurate in terms of the
      specific nursing actions that respond to the level of assistance required by the
      resident, both behaviourally and physically. RELEVANCE TO CLINICAL PRACTICE:
      Sound knowledge and reflective practices should be implemented by care workers of
      the nursing interventions that promote adequate oral fluid intake. Care plans
      should serve a dual purpose and facilitate communication between staff members
      and provide sufficient flexibility to allow for the contribution of novel ways in
      which to promote oral fluid intake while also being educative.

PMID- 18624782
TI  - Mental health care: trust and mistrust in different caring contexts.
AB  - AIMS AND OBJECTIVES: To identify the factors that make trust within the context
      of public mental health possible. We also consider the question of patients'
      trust in the whole caring system. The study is based on individual interviews
      with 22 psychiatric patients, who were also users of social services. BACKGROUND:
      There are theoretical studies concerning trust between human beings in several
      disciplines within psychiatry and social services but few studies investigate how
      trust can be created and what makes it possible. The literature reveals that
      there is need for research concerning trust in psychiatry. In this study we
      examined two different caring contexts and investigated what makes trust possible
      in these contexts. The contexts are termed the Integrated Network and Family
      Model and the Traditional Model. DESIGN: A qualitative method based on the
      grounded theory approach was used. METHODS: The main focus in the analysis was on
      how the patients had experienced the contexts of the caring systems and how trust
      was created or not within them. RESULTS: Three categories creating trust were
      found in the Integrated Network and Family Model and two in the Traditional
      context. Acceptance of the patient's expertise concerning his/her life situation,
      openness and joint discussions concerning knowledge are important. Trust is
      closely connected to autonomy and power: patients feel that trust increases as
      their experience of autonomy increases and in such situations power is not owned
      by any one person. CONCLUSIONS: Trust between psychiatric patients and personnel
      can be created in both the Integrated Network and Family Model and traditional
      context, but in different ways. RELEVANCE TO CLINICAL PRACTICE: Clinical workers
      and nursing personnel can use our findings in their practical work with
      psychiatric patients. Our findings support theoretical considerations concerning
      trust and can be used as guidelines for nursing personnel in their work.

PMID- 18624783
TI  - A systematic review of personality disorder amongst people with intellectual
      disability with implications for the mental health nurse practitioner.
AB  - AIMS AND OBJECTIVES: This paper reviews and summarises the literature on
      assessment, diagnosis and management of personality disorder in people with
      intellectual disability. It will proceed to argue the implications of a mental
      health nurse practitioner in clinical practice. BACKGROUND: Personality disorder
      is a potentially severe and disabling condition causing significant distress as
      well as presenting considerable challenges for service providers. Diagnosis in
      people with intellectual disability is controversial. However, it is considered
      that this population is at greater risk of these disorders. There is, however,
      little research on which to base clinical interventions or service planning.
      DESIGN: Systematic review. METHODS: A literature search of electronic data was
      undertaken in April 2007 using CINAHL, AMED, Medline, PsycINFO, EMBASE and
      Cochrane Library. Other sources included Google Scholar, hand searching of
      reference lists and texts and search of relevant websites. RESULTS: The
      literature on personality disorder in intellectual disability is notable for its
      paucity. The limited evidence available suggests that this population is at
      greater risk of personality disorder and that assessment and diagnosis is complex
      and often overshadowed by the intellectual disability. Few papers address
      treatment, there are no trial-based studies and it has not been established
      whether results can be extrapolated from research in the general population.
      CONCLUSIONS: The issue of personality disorder in people with intellectual
      disability is shrouded in controversy with a dearth of robust evidence to inform
      assessment or therapeutic care. Personality disorder does, however, provide a
      basis for decisions on type and intensity of support required for this population
      who have significant levels of unmet need. RELEVANCE TO CLINICAL PRACTICE: Some
      people with an intellectual disability and personality disorder can live in the
      community with specialist support. The mental health nurse practitioner has the
      potential to provide people with dual diagnostic support needed to enhance the
      capacity of the service system to meet the needs of this complex and difficult
      population.

PMID- 18624784
TI  - Women of advanced maternal age undergoing amniocentesis: a period of uncertainty.
AB  - AIMS: To generate a descriptive model for understanding patterns and
      interpretations concerning women's experiences of amniocentesis in Taiwan.
      BACKGROUND: In light of scientific technology and social change, it would be
      important to recognise the complexity of a woman's situation and the meaning of
      her in-depth experience while undergoing amniocentesis. Earlier studies on the
      experience of these women often relied on quantitative data obtained from
      questionnaires at only one point in time; however, the changes in older pregnant
      women, known to be at increased risk for foetal chromosomal abnormalities, from
      the time of pregnancy until test results of their amniocentesis has not been
      clearly understood. DESIGN: A grounded theory approach was applied. METHODS: Data
      were collected through in-depth interviews and participant observation. Sampling
      and major coding continued from 2002-2003 until theoretical saturation occurred;
      20 women (> or =35 years of age) participated in this study; data were analysed
      using constant comparative and content analysis. RESULTS: A prevailing sense of
      uncertainty was the core category for describing and guiding the process of this
      study with five main stages identified: (1) ambivalence toward pregnancy; (2)
      decision to undergo amniocentesis; (3) concerns regarding maternal and foetal
      safety during procedure; (4) anxiety while awaiting results and (5) thoughts
      about a lifetime maternal commitment. CONCLUSIONS: Identification and
      appreciation for emerging themes enables nurses to address women's concerns in a
      meaningful way as they undergo amniocentesis. Also, it is hoped that
      understanding key themes allows nurses to facilitate constructive interactions
      between women, physicians and other members of the obstetric team. RELEVANCE TO
      CLINICAL PRACTICE: Women in Taiwan undergoing amniocentesis had concerns about
      safety and dealt with cultural taboos of pregnancy in advanced age; health
      education should include coping strategies and decision making in dealing with
      these issues. To facilitate constructive interactions between clients and health
      care teams, the ethical guidance of informed consent and respecting the women's
      autonomy should be emphasised.

PMID- 18624785
TI  - Longitudinal biomonitoring of nurses handling antineoplastic drugs.
AB  - AIMS AND OBJECTIVES: To assess a possible trend in the genotoxic risk of
      oncologic nurses during the working year, cytogenetic biomonitoring was
      performed. BACKGROUND: Exposure to cytostatic agents is a major occupational
      concern in oncologic personnel. In contrast to the controlled environment in
      oncology pharmacies, nurses may be subject to unexpected events of exposure due
      to the intensive contact with patients. DESIGN AND METHODS: The entire nursing
      staff of an oncology inpatient ward (n = 15) participated in a biomonitoring
      study over a period of nine months using the sister chromatid exchange test and
      the comet assay to detect DNA strand breaks. Blood samples were taken after a
      three-week summer break (base level), one, three, six and nine months thereafter.
      Airborne contaminations of cytotoxics were addressed by chromatographic methods.
      RESULTS: With regard to the single monitoring points, the comet assay revealed no
      significant alteration of the genotoxic burden within nine months. By contrast,
      the sister chromatid exchange levels were significantly increased after six and
      nine months when compared with base levels. A trend analysis covering the whole
      observation period revealed an increase in genotoxicity as shown by the sister
      chromatid exchange test and the alkaline but not the neutral comet assay. This
      increase, however, was small and reversible as shown by the trend analysis of
      sister chromatid exchange rates during the years of service. Air samples were
      negative for cytotoxic contaminants. CONCLUSIONS AND RELEVANCE TO CLINICAL
      PRACTICE: The small, but statistically significant genotoxic burden observed in
      oncologic nurses of an inpatient ward emphasises the need for a continuing effort
      to eliminate residual occupational risks. In comparison with historical controls,
      the current situation is characterised by beneficial safety improvements over the
      last years. Nevertheless, periodic training and awareness of the problems should
      be an integral part of advanced education.

PMID- 18624786
TI  - Beliefs about appropriate pain behaviour: gender differences between health care
      professionals and non-health care professionals in Hong Kong.
AB  - AIMS: The purpose of this study was to examine the effects of participants'
      gender on their beliefs regarding gender-appropriate pain behaviour among health
      care professionals and non-health care professionals. BACKGROUND: Gender may
      influence beliefs about appropriate pain behaviour among health care
      professionals and non-health care professionals. METHODS: The study consisted of
      a survey of 152 participants, 38 male and 38 female health care professionals and
      38 male and 38 female non-health care professionals. Each participant completed
      both questionnaires, the Appropriate Pain Behaviour Questionnaire-Female (APBQ-F)
      and Appropriate Pain Behaviour Questionnaire-Male (APBQ-M). RESULTS: Occupation
      had a significant effect: the health care professionals rated pain behaviours as
      more acceptable in both genders than the non-health care professionals, F(1, 148)
      = 13.636, p < 0.01. Gender also had a significant effect: female participants
      considered pain behaviours more acceptable than male participants, F(1, 148) =
      5.056, p < 0.026. There was a significant effect between APBQ-M and APBQ-F: for
      both genders in both occupations, pain behaviours in women were rated as more
      acceptable than in men, F(1, 148) = 105.469, p < 0.005. CONCLUSIONS: Health care
      professionals would consider overt pain-related behaviours by both men and women
      to be more acceptable than non-health care professionals. Both genders and both
      occupations would consider overt pain-related behaviours to be more acceptable in
      women than in men. RELEVANCE TO CLINICAL PRACTICE: Health care professionals need
      to be aware that their attitude to pain behaviours may influence their management
      of patients and that different genders experience pain differently. This has
      clear implications in terms of clinical treatment and diagnosis.

PMID- 18624787
TI  - Gray matter deficits in young adults with narcolepsy.
AB  - OBJECTIVES: The aim of this study was to investigate gray matter volume changes
      in narcolepsy. MATERIALS AND METHODS: An optimized voxel-based morphometry was
      conducted for 17 young adults with a sole diagnosis of human leukocyte antigen
      DQB(1) 0602 positive narcolepsy with cataplexy (26.6 +/- 5.2 years old) and 17
      comparison subjects (24.6 +/- 4.9 years old) using 3 Tesla scanner. Gray matter
      volumes in the bilateral hypothalamic voxel of interests (VOI) were also
      calculated. RESULTS: Compared with the comparison subjects, narcoleptic patients
      had gray matter volume decrease in the right hypothalamus and other regions
      including subcortical, prefrontal, limbic and occipital areas. Narcoleptic
      patients also had lower gray matter volume on predefined VOI at the bilateral
      hypothalamus, which correlated with the Ullanlinna Narcolepsy Scale score.
      CONCLUSIONS: Current findings suggest that narcoleptic patients have structural
      abnormalities in hypothalamus, which might be related to the clinical
      manifestation of narcolepsy with cataplexy.

PMID- 18624788
TI  - Eosinophilic oesophagitis in patients presenting with dysphagia--a prospective
      analysis.
AB  - BACKGROUND: Eosinophilic oesophagitis (EoO) may be a common finding in adults
      presenting with dysphagia. AIM: To identify the risk factors and prevalence of
      EoO in an adult population with dysphagia. METHODS: All patients with dysphagia
      referred for an upper endoscopy (EGD) were asked to participate. Patients
      completed a detailed questionnaire followed by EGD with four quadrant biopsies in
      the distal and mid-oesophagus. Primary endpoint was the prevalence of EoO;
      secondary endpoints included age, gender, asthma, food allergies, gastro
      oesophageal reflux disease/dysphagia score and endoscopic findings. RESULTS: Two
      hundred and sixty-one patients enrolled between December 2005 and January 2007.
      Thirty-one patients (12%) met pathological criteria for EoO. There was no
      difference in EoO prevalence within each gender. Mean age of EoO patients was 42
      +/- 15 vs. 61 +/- 15 for non-EoO patients (P < 0.001). EoO was diagnosed in 35%
      of patients <50 years of age. EoO was present in 22% of asthmatics vs. 9% non
      asthmatics (P < 0.01). EoO was present in 36.8% of patients with self-reported
      food allergies vs. 9.3% those without allergy (P < 0.001). A 13/31(42%) of EoO
      patients did not have the classic EGD findings (rings +/- furrows) and would have
      been missed without oesophageal biopsies. CONCLUSIONS: Eosinophilic oesophagitis
      was diagnosed in 12% of the patients presenting with dysphagia with relative risk
      of 9.5 if age <50 years. Oesophageal biopsies are warranted in patients
      presenting with dysphagia especially in the younger population. Patients may not
      present with classic endoscopic findings and EoO can be missed without biopsies.

PMID- 18624791
TI  - Immunoblotting using multiple antigens is essential to  demonstrate the true risk
      of Helicobacter pylori infection  for gastric cancer.
AB  - BACKGROUND: Enzyme-linked immunosorbent assays (ELISAs) for detection of
      Helicobacter pylori infection, using IgG antibodies, may significantly
      underestimate the association with gastric cancer. AIM: To compare associations
      between H. pylori and cardia (CGC) and noncardia gastric cancer (NCGC) using
      ELISA and immunoblotting and determine the effect of atrophic gastritis on
      detection. METHODS: Nested case-control study within the Melbourne Collaborative
      Cohort Study. Helicobacter pylori antibodies were detected in subjects with CGC
      (n = 18), NCGC (n = 34) and controls (n = 69 and 134 respectively) using ELISA
      (pylori DTect) and immunoblot (Helicoblot 2.1). Pepsinogen I levels were measured
      using ELISA. RESULTS: Using ELISA, H. pylori-positivity in the CGC group was 33%
      vs. 35% in controls [odds ratio (OR = 0.9, 95% CI: 0.3-2.7)], while that in the
      NCGC group was 79% vs. 63% in controls [OR = 2.3 (95% CI: 0.9-5.8)]. Based on
      immunoblotting, H. pylori-positivity in the CGC group was 44% vs. 39% in their
      controls [OR = 1.2 (95% CI: 0.4-3.4)], while that in the NCGC group was 94% vs.
      63% in controls [OR = 10.6 (95% CI: 2.4-47.4)]. Pepsinogen I levels in the NCGC
      cases and controls showed the lowest median level (4 ng/mL) to be in subjects
      negative by ELISA but positive by immunoblotting. CONCLUSION: Immunoblotting
      improves the accuracy of H. pylori studies involving gastric cancer.

PMID- 18624793
TI  - Inter-laboratory assessment of PrPSc typing in creutzfeldt-jakob disease: a
      Western blot study within the NeuroPrion Consortium.
AB  - Molecular typing is of considerable importance for the surveillance and
      epidemiology of human transmissible spongiform encephalopathies (TSEs). It relies
      on the detection of distinct protease-resistant prion protein (PrP(Sc)) core
      fragments that differ in molecular mass and/or glycoform ratio. In this
      collaborative study, we tested the inter-laboratory agreement in TSE molecular
      typing. Sixteen characterized brain specimens from sporadic TSEs and variant
      Creutzfeldt-Jakob disease (vCJD) cases were distributed blindly to seven
      laboratories for molecular characterization by a defined protocol and
      classification. Agreement between laboratories in the classification of samples
      was excellent. In particular, there were no differences in the distinction
      between PrP(Sc) type 1, type 2A, and type 2B with one exception, which eventually
      was identified as a case with types 1 and 2 co-occurrence. This shows that the
      general technique and particular classification system used here are robust and
      represent a reliable basis for diagnostic and epidemiologic purposes. The subtle
      further distinction of subtypes among type 1 and type 2 groups requires high
      sensitivity gel electrophoresis protocols that are unsuitable for routine
      diagnostic needs and must be reserved for research investigations. Further
      research is necessary on the identification and significance of co-occurrence of
      PrP(Sc) types 1 and 2 within one brain.

PMID- 18624796
TI  - Successive post-translational modifications of E-cadherin are required for InlA
      mediated internalization of Listeria monocytogenes.
AB  - Listeria monocytogenes surface proteins internalin (Inl)A and InlB interact with
      the junctional protein E-cadherin and the hepatocyte growth factor (HGF) receptor
      Met, respectively, on the surface of epithelial cells to mediate bacterial entry.
      Here we show that InlA triggers two successive E-cadherin post-translational
      modifications, i.e. the Src-mediated tyrosine phosphorylation of E-cadherin
      followed by its ubiquitination by the ubiquitin-ligase Hakai. E-cadherin
      ubiquitination induces the recruitment of clathrin that is required for optimal
      bacterial internalization. We also show that the initial clustering of E-cadherin
      at the bacterial entry site requires caveolin, a protein normally involved in
      clathrin-independent endocytosis. Strikingly clathrin and caveolin are also
      recruited at the site of entry of E-cadherin-coated sepharose beads and
      functional experiments demonstrate that these two proteins are required for bead
      entry. Together these results not only document how the endocytosis machinery is
      recruited and involved in the internalization of a zippering bacterium, but also
      strongly suggest a functional link between E-cadherin endocytosis and the
      formation of adherens junctions in epithelial cells.

PMID- 18624794
TI  - Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of
      Alzheimer's disease patients.
AB  - Disturbed glutamate homeostasis may contribute to the pathological processes
      involved in Alzheimer's disease (AD). Once glutamate is released from synapses or
      from other intracellular sources, it is rapidly cleared by glutamate
      transporters. EAAC1 (also called EAAT3 or SLC1A1) is the primary glutamate
      transporter in forebrain neurons. In addition to transporting glutamate, EAAC1
      plays other roles in regulating GABA synthesis, reducing oxidative stress in
      neurons, and is important in supporting neuron viability. Currently, little is
      known about EAAC1 in AD. To address whether EAAC1 is disturbed in AD,
      immunohistochemistry was performed on tissue from hippocampus and frontal cortex
      of AD and normal control subjects matched for age and gender. While EAAC1
      immunostaining in cortex appeared comparable to controls, in the hippocampus,
      EAAC1 aberrantly accumulated in the cell bodies and proximal neuritic processes
      of CA2-CA3 pyramidal neurons in AD patients. Biochemical analyses showed that
      Triton X-100-insoluble EAAC1 was significantly increased in the hippocampus of AD
      patients compared to both controls and Parkinson's disease patients. These
      findings suggest that aberrant glutamate transporter expression is associated
      with AD-related neuropathology and that intracellular accumulation of detergent
      insoluble EAAC1 is a feature of the complex biochemical lesions in AD that
      include altered protein solubility.

PMID- 18624795
TI  - MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can
      be used to differentiate primary from metastatic brain tumors.
AB  - A recurring challenge for brain pathologists is to diagnose whether a brain
      malignancy is a primary tumor or a metastasis from some other tissue. The
      accurate diagnosis of brain malignancies is essential for selection of proper
      treatment. MicroRNAs are a class of small non-coding RNA species that regulate
      gene expression; many exhibit tissue-specific expression and are misregulated in
      cancer. Using microRNA expression profiling, we found that hsa-miR-92b and hsa
      miR-9/hsa-miR-9* are over-expressed, specifically in brain primary tumors, as
      compared to primary tumors from other tissues and their metastases to the brain.
      By considering the expression of only these two microRNAs, it is possible to
      distinguish between primary and metastatic brain tumors with very high accuracy.
      These microRNAs thus represent excellent biomarkers for brain primary tumors.
      Previous reports have found that hsa-miR-92b and hsa-miR-9/hsa-miR-9* are
      expressed more strongly in developing neurons and brain than in adult brain.
      Thus, their specific over-expression in brain primary tumors supports a
      functional role for these microRNAs or a link between neuronal stem cells and
      brain tumorigenesis.

PMID- 18624797
TI  - Differential modulation of innate immune cell functions by the Burkholderia
      cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans
      disrupts maturation and induces necrosis in human dendritic cells.
AB  - Burkholderia cepacia complex (BCC) bacteria cause pulmonary infections that can
      evolve into fatal overwhelming septicemia in chronic granulomatous disease or
      cystic fibrosis patients. Burkholderia cenocepacia and Burkholderia multivorans
      are responsible for the majority of BCC infections in cystic fibrosis patients,
      but B. cenocepacia is generally associated with a poorer prognosis than B.
      multivorans. The present study investigated whether these pathogens could
      modulate the normal functions of primary human monocyte-derived dendritic cells
      (DCs), important phagocytic cells that act as critical orchestrators of the
      immune response. Effects of the bacteria on maturation of DCs were determined
      using flow cytometry. DCs co-incubated for 24 h with B. cenocepacia, but not B.
      multivorans, had reduced expression of costimulatory molecules when compared with
      standard BCC lipopolysaccharide-matured DCs. B. cenocepacia, but not B.
      multivorans, also induced necrosis in DCs after 24 h, as determined by annexin V
      and propidium iodide staining. DC necrosis only occurred after phagocytosis of
      live B. cenocepacia; DCs exposed to heat-killed bacteria, bacterial supernatant
      or those pre-treated with cytochalasin D then exposed to live bacteria remained
      viable. The ability of B. cenocepacia to interfere with normal DC maturation and
      induce necrosis may contribute to its pathogenicity in susceptible hosts.

PMID- 18624798
TI  - Effects of pregnancy on slow cortical potentials in migraine patients and healthy
      controls.
AB  - Increased negative amplitudes and lack of habituation of contingent negative
      variation (CNV) in migraine are well established and are supposed to reflect an
      altered cortical excitability level. Migraine attacks occur less during pregnancy
      but often relapse after delivery. We investigated the effect of pregnancy on slow
      cortical potentials and reaction time in migraine patients and healthy controls.
      Four groups were examined: 14 pregnant migraine patients, 12 non-pregnant
      migraine patients, 15 pregnant healthy women and 16 non-pregnant healthy women
      aged 19-38 years. Two recordings were performed in the pregnant subjects: in the
      36th week of gestation and 4 weeks after delivery. The non-pregnant subjects were
      recorded at the same time interval of 8 weeks. Pregnant migraine patients showed
      significantly fewer migraine days during the third trimester of pregnancy and
      returned to nearly the former level 4 weeks post delivery. Non-pregnant migraine
      patients demonstrated a significant reduction of migraine days at the second
      measurement. There was no effect of pregnancy on CNV amplitudes, but there was an
      effect of pregnancy on the habituation coefficient and reaction time of migraine
      patients. Faster habituation from a higher preactivation level was found. As an
      explanation for the changed habituation level we favour the model of correlation
      between preactivation level and habituation level, the so-called law of initial
      value. We found a correlation between preactivation level and habituation. Our
      study confirms a specific effect of pregnancy on slow cortical potentials in
      migraine patients.

PMID- 18624799
TI  - Exertional headache: a new venous disease.

PMID- 18624800
TI  - Migraine and antiphospholipid antibodies: no association found in migraine
      discordant monozygotic twins.
AB  - Migraine headache (with and without aura) is common in the general population and
      is known to be influenced by genetic factors with heritability estimates between
      34-57%. Antiphospholipid syndrome (APS) is a hypercoagulable state characterized
      by clinical features including venous and arterial thromboses, pregnancy loss and
      migraine, and by association with antiphospholipid antibodies (aPL). Numerous
      small studies have investigated whether aPL are associated with migraine in the
      general population--with contradictory results. In this study, the question was
      addressed by studying the prevalence of aPL in members of monozygotic (MZ) twin
      pairs differing in their migraine status. Such twins provide a unique natural
      experiment, matched as they are for age, sex and genetic factors, and allow the
      role of environmental factors, such as aPL, to be determined. Despite 95% power
      to detect a difference of 0.59 IgG units per litre in anticardiolipin antibody
      IgG titres, no difference in prevalence of aPL could be detected in migraine
      discordant MZ twins.

PMID- 18624801
TI  - Difference in triptan effect in patients with migraine and early allodynia.
AB  - The aim of this study was to determine whether in migraine patients with and
      without aura early treatment with various triptans leads to differences in pain
      reduction after 1 h and in modulating cutaneous allodynia. Thirty-six patients
      with early manifestation of a clinically recognizable allodynia of the face and
      non-responders to earlier treatment with sumatriptan 100 mg were included.
      Patients were randomized to six triptan treatment groups. Significant pain
      reduction was seen only in the group receiving zolmitriptan nasal spray 5 mg with
      a mean visual analogue scale (VAS) score of 3.8 (s.d. 1.2) at baseline and 2.4
      (s.d. 1.3; P = 0.015) at 1 h after using the triptan and was thus a predictor of
      a VAS score 3 within 1 h. The study results indicate that migraine headache
      intensity can be reduced within 1 h by using zolmitriptan 5 mg nasal spray in
      spite of the presence of early cutaneous allodynia.

PMID- 18624802
TI  - Abnormalities of the vestibulo-collic reflex are similar in migraineurs with and
      without vertigo.
AB  - The amplitude and habituation of the click-evoked vestibulo-collic reflex (VCR)
      was found reduced between attacks in migraineurs without complaints of ictal or
      interictal vertigo or dizziness, compared with healthy subjects. As a next step
      we recorded VCR in 17 migraine patients (eight with migraine without aura and
      nine with migraine with aura) who presented ictal migrainous vertigo according to
      the criteria defined by Neuhauser et al., using a method described previously.
      Migraineurs with migrainous vertigo have similar VCR abnormalities as patients
      without vertigo, i.e. a decreased global amplitude and absence of habituation.
      Potentiation seemed more pronounced in migraineurs with vertigo (7.46 +/- 18.6),
      but the difference was not significant.

PMID- 18624803
TI  - Acupuncture in patients with headache.
AB  - We aimed to investigate the effectiveness of acupuncture in addition to routine
      care in patients with primary headache (> 12 months, two or more headaches/month)
      compared with treatment with routine care alone and whether the effects of
      acupuncture differ in randomized and non-randomized patients. In a randomized
      controlled trial plus non-randomized cohort, patients with headache were
      allocated to receive up to 15 acupuncture sessions over 3 months or to a control
      group receiving no acupuncture during the first 3 months. Patients who did not
      consent to randomization received acupuncture treatment immediately. All subjects
      were allowed usual medical care in addition to study treatment. Number of days
      with headache, intensity of pain and health-related quality of life (SF-36) were
      assessed at baseline, and after 3 and 6 months using standardized questionnaires.
      Of 15,056 headache patients (mean age 44.1 +/- 12.8 years, 77% female), 1613 were
      randomized to acupuncture and 1569 to control, and 11,874 included in the non
      randomized acupuncture group. At 3 months, the number of days with headache
      decreased from 8.4 +/- 7.2 (estimated mean +/-s.e.) to 4.7 +/- 5.6 in the
      acupuncture group and from 8.1 +/- 6.8 to 7.5 +/- 6.3 in the control group (P <
      0.001). Similarly, intensity of pain and quality of life improvements were more
      pronounced in the acupuncture vs. control group (P < 0.001). Treatment success
      was maintained through 6 months. The outcome changes in non-randomized patients
      were similar to those in randomized patients. Acupuncture plus routine care in
      patients with headache was associated with marked clinical improvements compared
      with routine care alone.

PMID- 18624804
TI  - The usefulness and applicability of a basic headache diary before first
      consultation: results of a pilot study conducted in two centres.
AB  - We tested the usefulness and applicability of a simplified headache diary in the
      diagnosis of migraine (M), tension-type headache (TTH) and medication overuse
      headache (MOH). The diary was given to headache patients before their first
      consultation at the headache centre. Seventy-six naive headache patients
      completed the study. Their understanding of the diary proved highly satisfactory.
      The patients' level of compliance was also good, with 71% returning the diary
      completely filled in. The data entered in the diary were deemed complete for the
      diagnostic purpose in 93% of cases. The level of agreement between headache
      information gathered through clinical interview and the headache diary was
      satisfactory. When comparing the diary with the clinical interview, sensitivity
      was 92% for M, 75% for TTH and MOH. Specificity was 58% for M and TTH, 87% for
      MOH. Combined use of a diagnostic diary and clinical interview is recommended
      from the first consultation for headache.

PMID- 18624805
TI  - Quantitative EEG power and asymmetry increase 36 h before a migraine attack.
AB  - The aim was to estimate ictal, pre- and postictal brain function changes in
      migraine in a blinded paired quantitative EEG (QEEG) study. EEG recordings (n =
      119) from 40 migraineurs were retrospectively classified as ictal, interictal,
      preictal or postictal. delta, theta, alpha and beta power, and hemispheric
      asymmetry in frontocentral, temporal and occipitoparietal regions were calculated
      from artefact-free EEG. Power and power asymmetry were calculated for two time
      windows, 36 and 72 h before/after the attack, and compared with the interictal
      values. Frontocentral delta power increased (P = 0.03), whereas frontocentral
      theta and alpha power tended to increase (P < 0.09) within 36 h before the next
      attack compared with the interictal period. Occipitoparietal (alpha and theta)
      and temporal (alpha) power were more asymmetric before the attack compared with
      the interictal baseline (P < 0.04). Ictal posterior alpha power increased
      slightly (P = 0.01). Postictal power and power asymmetry were not significantly
      different from interictal baseline. EEG activity seems to change shortly before
      the attack. This suggests that migraineurs are most susceptible to attack when
      anterior QEEG delta power and posterior alpha and theta asymmetry values are
      high. Changed activity patterns in cholinergic brainstem or basal forebrain
      nuclei and thalamo-cortical connections before the migraine attack are
      hypothesized.

PMID- 18624806
TI  - A 13-year long-term outcome study of elderly with chronic daily headache.
AB  - We established a cohort of 60 subjects with chronic daily headache (CDH) out of
      1533 community-based elderly in 1993 and finished two short-term follow-ups in
      1995 and 1997. All of the 26 survivors without dementia (4 M/22 F, mean age 82.7
      +/- 3.4 years) finished the follow-up in 2006. The mean headache frequency was
      8.4 +/- 11.8 days per month in the past year, and seven (27%) had persistent CDH.
      Based on the International Classification of Headache Disorders, 2nd edn, the CDH
      subtypes diagnoses were chronic migraine in three subjects, chronic tension-type
      headache in three, and one with medication-overuse headache. All these seven
      subjects had CDH during the 1995 and 1997 follow-ups. The diagnosis of CDH with
      migrainous features increased from 25 to 71% in those with CDH from 1993 to 2006.
      Migraine was the most common headache type in those with CDH resolution.
      Aggressive treatment should be applied especially for those with persistent CDH
      at short-term follow-ups.

PMID- 18624807
TI  - 'Bad trips': airplane headache not just in airplanes?
AB  - A type of headache associated with altitude variations in airplane travellers is
      increasingly reported and has recently become a subject of debate for experts. We
      present a patient with headache related to altitude variations in two different
      settings: airplane and mountain descent, suggesting that different kinds of
      triggers for pressure variation can cause the same type of pain.

PMID- 18624808
TI  - Reduced habituation of trigeminal reflexes in patients with episodic cluster
      headache during cluster period.
AB  - A growing body of evidence supports the pivotal role of the hypothalamus in the
      pathophysiology of cluster headache (CH). On the basis of animal studies, it has
      been suggested that a hypothalamic dysfunction can lead to a habituation deficit
      of brainstem reflex responses, as result of a stress-like condition. Taking into
      account these findings, we tested the hypothesis that habituation of brainstem
      reflexes may be impaired in CH patients. The habituation phenomenon of the late
      components (R2 and R3) of the blink reflex was studied in 27 CH patients during
      the cluster period, in 22 migraine patients interictally and in 20 control
      subjects. A significant habituation deficit in the R2 and R3 components was found
      in CH compared with both controls and migraineurs. The lack of habituation in CH,
      more pronounced than in migraine, points to abnormal processing of sensory
      stimuli at the trigeminal level that could be driven by hypothalamic dysfunction
      during the cluster period.

PMID- 18624809
TI  - Increased risk for coeliac disease in paediatric patients with migraine.
AB  - The aim was to determine the prevalence of coeliac disease (CD) in paediatric
      patients with migraine. Serum tissue transglutaminase IgA (tTGA) antibodies and
      IgA concentrations were measured in 73 patients with migraine (age range 6-17
      years) and the control group (n = 147). Patients having positive tTGA antibodies
      underwent duodenal biopsy. Four patients (5.5%) from the study group and one
      (0.6%) from the control group had positive tTGA antibody titres (P < 0.05). Three
      patients with migraine had normal duodenal histology and were considered as
      potential CD. One patient from the study group and one from the control group
      declined to have biopsy. tTGA antibody is considered as a reliable indicator for
      the presence of CD. However, some patients with positive antibodies may have
      normal biopsy initially and are classified as having potential CD. Our finding of
      a higher prevalance of tTGA antibodies in paediatric migraine patients suggests
      that an association between migraine and CD might exist.

PMID- 18624810
TI  - 2-(2,6-Dihalo-phenyl)-3-heteroaryl-2-ylmethyl-1, 3-thiazolidin-4-ones: anti-HIV
      agents.
AB  - A diversity of novel 2-aryl-3-heteroaryl-2-ylmethyl-1,3-thiazolidin-4-ones were
      designed and synthesized by reacting heteroaryl-2-ylmethyl amine with various 2,6
      dihalosubstituted benzaldehydes and mercaptoacetic acid. The title compounds were
      evaluated for human immunodeficiency virus type-1 (HIV-1) reverse transcriptase
      (RT) inhibitory activity. The results of in vitro assays showed that some of the
      compounds were effective inhibitors of HIV-1 reverse transcriptase enzyme at
      micromolar concentrations with less cytotoxicity in both MT-4 cells as well as
      acutely infected human T-lymphoid CEM cells. Compounds 4h and 4k emerged as
      moderately more potent with EC(50) are at 0.20 and 0.21 microM as compared to
      reference parent compound thiazolobenzimidazoles EC(50) 0.35 microM in MT-4
      cells.

PMID- 18624811
TI  - Effective mast cell degranulating peptide inhibitors of the IgE/Fc epsilonRI
      receptor interaction.
AB  - Previous studies with mast cell degranulating (MCD) peptide have shown that
      peptide [Ala(12)]MCD 8 was an inhibitor of IgE binding to mast cell receptors. In
      an attempt to produce increased inhibition, analogs were synthesized that
      maintained the alanine residue in position 12 in the MCD peptide sequence and
      were further modified at both termini. Analogs modified at the C-terminus were
      [Ala(12),desLys(21)]MCD 2 and [Ala(12),D-Lys(21)]MCD 4. N-terminus modifications
      were [desLys(6)-Arg(7)-His(8),Ala(12)]MCD 1, [Ala(6), Ala(12)]MCD 6, and
      [Val(6),Ala(12)]MCD 7. To assess the role of the Proline(12), analogs [D
      Ala(12)]MCD 3 and [Meleu(12)]MCD 5 were also synthesized. The analogs were tested
      for binding to the IgE receptor in cultured mast cells. Inhibitory activity of
      IgE-caused degranulation was measured using a beta-hexosaminidase assay. Circular
      dichroism (CD) and molecular modeling of selected analogs were used to follow
      possible structural differences among these analogs. All analogs showed binding
      affinity to the IgE receptor and inhibition of IgE-induced mast cell
      degranulation at different levels. Differences in inhibition were most likely
      because of diverse interactions of the analogs with the receptor as inferred by
      the CD and modeling studies. Based on the results of the beta-hexosaminidase
      assay, analog [Val(6), Ala(12)]MCD 7 proved to be an excellent inhibitor of IgE
      mediated mast cell degranulation.

PMID- 18624812
TI  - CXCR4, inhibitors and mechanisms of action.
AB  - In this review, the author discusses recent advances in anti-HIV inhibitors,
      targeting CXCR4, including natural and modified chemokines, peptides and organic
      compounds, their mechanisms of action, and the molecular process of virus
      invasion of immune cells. Peptides with strong anti-HIV activity exhibit several
      common features, such as electrostatic charges, cyclization, beta-turns and
      dimerization induced by a sulphide bond. Organic compounds, such as cyclams,
      display a unique metal-mediated mechanism in the binding process to its target
      CXCR4. Understanding of their mechanisms of action may be useful for the design
      of more effective drugs. Consecutive interactions of viral glycoprotein gp120
      with CD4 and the co-receptor, CXCR4 or another co-receptor CCR5 on the cell
      surface leads to virus invasion into host cells. The molecular details of the
      binding between HIV glycoproteins and the co-receptors also provide a basis for
      anti-HIV therapy.

PMID- 18624813
TI  - Comparative study to determine the need for intraoperative colonic irrigation for
      primary anastomosis in left-sided colonic emergencies.
AB  - OBJECTIVE: To compare the outcome of resection and primary anastomoses in
      patients undergoing emergency surgery of the left colon with and without
      intraoperative colonic irrigation. METHOD: From January 2004 to December 2006,
      102 consecutive patients with acute occlusion or perforation of the left colon
      were operated on an emergency basis in two Coloproctology units. According to the
      sample size calculation, 61 patients from one unit underwent surgery with
      intraoperative colonic irrigation, whereas 41 patients from the second unit
      underwent surgery without intraoperative colonic irrigation. The endpoints were
      mortality and morbidity. RESULTS: Thirty (49.2%) patients with intraoperative
      colonic irrigation and 8 (19.5%) without colonic irrigation developed one or more
      complications postoperatively (odds ratio 4.0, 95% CI 1.6-10.0, P = 0.002). An
      increased number of wound infections was seen in the group managed with colonic
      irrigation 15 vs 3 (P = 0.034). The postoperative mortality rate and the
      occurrence of dehiscence of the anastomoses were similar in both study groups.
      CONCLUSION: The present findings indicate that resection and primary anastomosis
      in patients undergoing emergency surgery of the left colon can be safely
      performed without intraoperative colonic irrigation.

PMID- 18624814
TI  - Circumferential stapled procedure for bleeding ano-rectal varices is an effective
      treatment--experience in nine patients.
AB  - OBJECTIVE: The objective of this study was to demonstrate that stapled disruption
      of rectal varices is a feasible and suitable method of controlling bleeding
      varices. METHOD: Patients known to have bleeding rectal varices secondary to
      liver failure were offered this procedure. All these patients had failed medical
      and endoscopic management. All nine patients underwent the procedure as an
      emergency, with the intention of controlling haemorrhage. The procedure was
      carried out under general anaesthetic by a colorectal surgeon experienced in
      using the stapled device for haemorrhoidectomy. RESULTS: Nine patients underwent
      this procedure, with successful control of bleeding achieved in all. Follow-up
      period from 4 to 24 months revealed no further re-bleeding. CONCLUSION: We
      conclude that stapled disruption of bleeding rectal varices in patients with
      known portal hypertension is a very useful and effective procedure when carried
      out by an experienced colorectal surgeon.

PMID- 18624815
TI  - Perineum compression during EAUS enhances visualization of anterior anal
      sphincter defects.
AB  - OBJECTIVE: Endo-anal ultrasound (EAUS) can detect anal sphincter injuries.
      However, anterior external anal sphincter (EAS) defects can be difficult to
      define. We assessed different EAUS techniques to determine if any particular
      method improved defect identification. METHOD: Ninety females with faecal
      incontinence were prospectively studied. Wexner faecal incontinence scores were
      obtained. All patients underwent anorectal manometry and EAUS using three
      different techniques: standard, digit-assisted (gloved finger pressing on
      posterior vaginal wall) and balloon-assisted (standard balloon inflated into the
      vagina). The three techniques were assessed by comparing defect characteristics
      (detection, angle, edges and scar tissue), and perineal body thickness. All
      measurements were performed at the mid anal canal level. RESULTS: are expressed
      as medians (IQR). Results Standard EAUS (S-EAUS) identified a sphincter defect in
      54 patients. Digit assisted EAUS (D-EAUS) and balloon-assisted EAUS (B-EAUS)
      ultrasound revealed a sphincter defect in additional 11 and 9 patients
      respectively compared to S-EAUS. Correlation of maximum squeeze pressure with
      EAUS findings improved on D-EAUS and B-EAUS. The defect angle was significantly
      wider with D-EAUS and B-EAUS [S-EAUS 90 degrees (63-97), D-EAUS 100 degrees (81
      101.5), B-EAUS 100 degrees (80-105), P = 0.0005]. The perineal body was
      significantly thicker when measured with B-EAUS [D-EAUS 9 mm (7-10) vs B-EAUS 10
      mm (8-11), P = 0.0005]. Inter-observer agreement was comparable [S-EAUS (K) =
      0.677, D-EAUS (K) = 0.658, B-EAUS (K) = 0.601]. CONCLUSION: EAS anterior defect
      detection and definition on EAUS may be improved by the demarcation and gentle
      pressure on the posterior vaginal wall.

PMID- 18624816
TI  - Preoperative investigations for metastatic staging of colon and rectal cancer
      across multiple centres--what is current practice?
AB  - OBJECTIVE: The optimal strategy for elective distant staging of colorectal
      carcinoma (CRC) has yet to be defined, with current guidelines based on small and
      limited series. One specific issue requiring review is the value of routine
      computerized tomographic (CT) chest examination. Also lacking is data on current
      routine clinical practice. METHOD: A retrospective chart review of consecutive
      cases of elective surgery for CRC from five hospitals. RESULTS: Two hundred and
      fifty-seven cases were reviewed, 128 colon and 129 rectal primaries. 164 (64%) of
      patients overall, ranging from 45% to 88% across the individual centres, had a
      preoperative serum CEA level performed. CT abdomen/pelvis was performed in 222
      (86%) of cases, ranging from 69% to 98% per centre. CT chest was performed in 95
      (37%) of cases, 47% of rectal vs 29% of colon cancers (P = 0.004). In 17 cases
      (18%) CT chest examinations revealed abnormalities suspicious for metastatic
      disease, leading to a change in management in six (35%) of these cases. Of the 17
      cases with an abnormal CT chest, in only 5 of the 14 (36%) where carcinoembryonic
      antigen (CEA) levels were also recorded was this increased, and in only three
      (21%) was this markedly (> 10 microg/l) elevated. CONCLUSIONS: Substantial
      variability exists in the preoperative evaluation of patients with CRC. Many
      patients do not have a CEA and/or abdominal imaging performed. Where performed,
      CT chest revealed suspicious findings in a significant number of patients, the
      vast majority of whom had a normal or near normal CEA. Future studies are
      required to define optimal preoperative staging.

PMID- 18624817
TI  - Short term outcome after emergency and elective surgery for colon cancer.
AB  - OBJECTIVE: Emergency presentation of colon cancer is common and associated with
      high mortality and morbidity following surgical treatment. The purpose of this
      study was to evaluate postoperative mortality and complications in a consecutive
      and population based series. METHOD: All patients with adenocarcinoma of the
      colon diagnosed between 1993 and 2007 were registered prospectively.
      Postoperative mortality and complication rates in elective and emergency patients
      were compared. Logistic regression analysis was used to identify independent risk
      factors for postoperative complications. RESULTS: In the study period 1129
      patients were admitted, of whom 279 (25%) presented as an emergency. A total of
      999 (89%) patients underwent surgical treatment; 924 patients (82%) had a major
      resection. The mortality rate was 3.5% after elective and 10% after emergency
      operation with resection (P < 0.01), and the complication rate was 24% and 38% (P
      < 0.01), respectively. In patients with left-sided obstruction, the mortality
      rate after Hartmann's procedure was 19% compared to 3% after resection with
      primary anastomosis (P < 0.01). Multivariate analyses demonstrated that emergency
      operation, increasing age, advanced tumour stage and ASA class IV were
      independent risk factors for postoperative mortality. CONCLUSION: Emergency
      operation for colon cancer was associated with high rates of complications and
      mortality, indicating that immediate surgery should be avoided if possible.
      Decompression of left sided obstruction with a stent seems promising, whereas no
      conclusion can be made with regard to optimal procedure if stent placement fails;
      in this study Hartmann's procedure was associated with high mortality and
      morbidity.

PMID- 18624818
TI  - Plasma magnesium should be monitored perioperatively in patients undergoing
      colorectal resection.
AB  - OBJECTIVE: Hypomagnesemia has been shown to have several clinically important
      sequelae. The aims of this study were: to assess the impact of bowel preparation,
      with sodium picosulphate (Picolax), on plasma electrolytes, with particular
      regard to plasma magnesium, in patients undergoing bowel preparation for
      colonoscopy and colorectal resection and to evaluate the influence of
      perioperative magnesium levels on postoperative cardiac dysrhythmias. METHOD:
      Sixty-one patients receiving sodium picosulphate (Picolax) bowel preparation were
      studied in two groups: Colonoscopy (31 patients) and Colorectal resection (30
      patients). Plasma sodium, potassium, magnesium, calcium, urea, creatinine and
      blood haematocrit were measured in all patients prior to commencement of bowel
      preparation, at the time of colonoscopy or colorectal resection and 24 h
      postoperatively (surgery group only). Mean electrolyte and haematocrit levels
      were then compared. Postoperative cardiac dysrhythmias were recorded and
      analysed. RESULTS: No significant changes following bowel preparation were
      observed in plasma sodium, potassium, calcium or creatinine. Plasma urea fell
      following bowel preparation (colonoscopy P < 0.001, resection P = 0.004) and rose
      following resection (P = 0.002). Magnesium levels increased following bowel
      preparation in both groups (colonoscopy P < 0.001, resection P = 0.007) and fell
      following resection (P < 0.001). Thirty-four per cent (21/60 patients) were
      hypermagnesemic following bowel preparation and 20% (6/30 patients) became
      hypomagnesemic following surgery. Postoperative cardiac dysrhythmias were
      associated with lower magnesium levels at induction and postoperatively (P =
      0.022 and P = 0.033). CONCLUSION: Bowel preparation with Picolax does not appear
      to cause significant electrolyte disturbance, except in elevating plasma
      magnesium. Postcolorectal resection plasma magnesium dropped significantly
      suggesting perioperative monitoring and replacement should be routine following
      colorectal surgery.

PMID- 18624819
TI  - Programming InterStim for faecal incontinence.
AB  - OBJECTIVE: Sacral nerve stimulation (SNS) for faecal incontinence (FI) is
      achieved by implanting a pulse generator attached to a tined lead with
      individually programmable electrodes. Our aim was to establish whether the
      'ideal' programme for the treatment of FI has been used most commonly. We also
      wished to determine whether re-programming changed the symptom severity scores.
      METHOD: The following data were extracted from our SNS patient database: the
      frequency with which each programme was used, the length of time it was effective
      for, the number of months from implantation that the programme was started and
      the symptom severity scores prior to a change or no change in programme. RESULTS:
      Thirty-eight patients have had implanted pulse generators inserted since 2004.
      One hundred and two programme changes were documented in the database. The
      'ideal' programme was not most commonly programmed. The common programmes were
      effective for longest. The electrode furthest from the tip was used in the
      initial programme only once and the median duration from implantation to the
      start of a programme including it is 13 months. Symptom severity scores were
      significantly higher in patients who required re-programming than in those whose
      programme remained unchanged. CONCLUSIONS: In our patients the 'ideal' programme
      was not the programme used most frequently, nor for the longest duration. The
      theoretical migration of the tined lead inwards with time is upheld by our
      results. Patients who feel the sensation of SNS perianally have lower symptom
      scores than those who do not and who require re-programming.

PMID- 18624820
TI  - Septic arthritis of the hip: a rare complication of fistulizing Crohn's disease.

PMID- 18624821
TI  - Systematic review of economic evaluations of laparoscopic surgery for colorectal
      cancer.
AB  - OBJECTIVE: Colorectal cancer is one of the most common cancers and the standard
      surgical treatment for this cancer is open resection (OS), but laparoscopic
      surgery (LS) may be an alternative treatment. In 2000, a Health Technology
      Assessment (HTA) review found little evidence on costs and cost-effectiveness in
      comparing the two methods. The evidence base has since expanded and this study
      systematically reviews the economic evaluations on the subject published since
      2000. METHOD: Systematic review of studies reporting costs and outcomes of LS vs
      OS for colorectal cancer. National Health Service Economic Evaluation Database
      (NHS EED) methods for abstract writing were followed. Studies were summarized and
      incremental cost-effectiveness ratios (ICER) for common outcomes were calculated.
      RESULTS: Five studies met the inclusion criteria. LS generally had higher
      healthcare costs. Most studies reported longer operational time and shorter
      length of stay and similar long-term outcomes with LS vs OS. Only one outcome,
      complications, was common across all studies but results lacked consistency (e.g.
      in two studies, OS was less costly but more effective; in another study, LS was
      less costly but more effective; and in the further two studies, LS could
      potentially be cost effective depending on the decision-makers' willingness to
      pay for the health gain). CONCLUSION: The evidence on cost-effectiveness is not
      consistent. LS was generally more costly than OS. However, the effectiveness data
      used in individual economic evaluation were imprecise and unreliable when
      compared with data from systematic reviews of effectiveness. Nevertheless, short
      term benefits of LS (e.g. shorter recovery) may make LS appear less costly when
      productivity gains are considered.

PMID- 18624822
TI  - Do patients require outpatient follow-up after rapid referral double contrast
      barium enema?
AB  - INTRODUCTION: In our hospital, patients above the age of 40 years referred with a
      change in bowel habit without rectal bleeding undergo a double contrast barium
      enema (DCBE) ideally within 2 weeks. Results of benign studies are sent to a
      consultant colorectal surgeon and a routine clinic visit arranged. The aim of
      this study was to identify whether, following DCBE, patients (i) presented at a
      later date with colorectal cancer and (ii) needed assessment in clinic. METHOD:
      This is a review looking at all patients who underwent DCBE prior to routine
      clinic visit between January 2004 and December 2005. Hospital databases were
      cross-referenced to identify any patients presenting with a new diagnosis of
      colorectal malignancy between DCBE and April 2007. Clinic letters were reviewed
      to identify the number of outpatient visits prior to discharge and reasons for
      continued follow-up. RESULTS: During the study period, 521 patients (age range 31
      93 years, 316 female) had DCBE prior to assessment in clinic. Diagnoses: cancer
      48 (9.2%), polyps 13 (2.5%), colitis 3 (0.6%), no significant pathology 457
      (87.7%). Of this latter cohort, 387 (84.7%) were discharged after one clinic
      visit; 54 (11.9%) attended twice and 11 (2.4%) were seen more than twice. Reasons
      for multiple attendances were management of haemorrhoids/anal fissure or
      investigations of unrelated symptoms. No new cancers were identified in this
      cohort between January 2004 and April 2007. CONCLUSION: Double contrast barium
      enema is a safe screening tool following a '2-week rule' referral with CIBH.
      Following a report of no significant pathology, there is no need to arrange
      routine follow-up.

PMID- 18624823
TI  - A cohort study of results following elective colonic and rectal resection within
      an enhanced recovery programme.
AB  - OBJECTIVE: The use of laparoscopic surgery coupled with an enhanced recovery
      programme (ERP) has resulted in hospital stays of 4 or less days for colonic and
      6 days following rectal resection, in previously reported small selected groups
      of patients. This report analyses an unselected cohort to determine if such
      benefits are reproducible. METHOD: Consecutive patients undergoing elective
      colonic or rectal surgery at a single centre between January 2002 and January
      2006 were followed. All were included in the ERP and underwent either
      laparoscopic or open surgery. RESULTS: The study group comprised 241 patients
      (mean age of 67 +/- standard deviation 14 years and 49% male sex distribution)
      who underwent elective colorectal resection within the context of an ERP. One
      hundred and fifty-one (62.7%) patients had malignant disease. Overall, 191
      (79.3%) patients underwent a laparoscopic procedure and the remaining underwent
      an open operation. Postoperative stay was shorter in patients undergoing
      laparoscopic vs open, colonic surgery (4 days vs 6 days, P = 0.002). A
      nonsignificant trend towards reduced postoperative stay was observed for patients
      undergoing laparoscopic vs open, rectal surgery (6 days vs 9 days, P = 0.088).
      Patients undergoing laparoscopic colectomy demonstrated significantly lower 30
      day mortality rates than those undergoing traditional colectomy (3/131 vs 3/39, P
      = 0.049). CONCLUSION: Laparoscopic colonic surgery in the context of an ERP
      offers reduced hospital stay and may confer a survival advantage over traditional
      techniques. These results confirm that previously reported benefits of
      laparoscopic surgery are reproducible within an unselected population.

PMID- 18624828
TI  - The microvascular architecture of the choroid plexus in fetal human brain lateral
      ventricle: a scanning electron microscopy study of corrosion casts.
AB  - The microvascular architecture of developing lateral ventricle choroid plexus was
      investigated by corrosion casting and scanning electron microscopy in human
      fetuses aged 20 gestational weeks. The areas with different microvascular
      patterns corresponded to the particular parts of the mature plexus: anterior
      part, glomus, posterior part, the villous fringe and the free margin. In the
      posterior part, densely packed parallel arterioles and venules were surrounded by
      sheath-like capillary networks. Other areas contained compact capillary plexuses
      of the primary villi: the most prominent, protruding basket- and leaf-shaped
      plexuses were observed in the villous fringe, whilst less numerous and smaller
      plexuses occurred in the anterior part and glomus. The capillaries of the
      plexuses had a large diameter and sinusoidal dilations, and showed the presence
      of occasional short, blind sprouts indicative of angiogenesis. Short anastomoses
      between arterioles supplying the plexuses and venules draining them were only
      rarely observed. In the upper area of the choroid plexus, the superior choroidal
      vein was surrounded by a capillary network forming small, glomerular or rosette
      shapes plexuses. The free margin of the choroid plexus was characterized by flat,
      multiple, arcade-like capillary loops. The general vascular architecture of the
      human choroid plexus at 20 gestational weeks seems to be similar to that of
      postnatal/mature plexus, still lacking, however, the complex vascular plexuses of
      the secondary villi.

PMID- 18624829
TI  - Human 2D (index) and 4D (ring) finger lengths and ratios: cross-sectional data on
      linear growth patterns, sexual dimorphism and lateral asymmetry from 4 to 60
      years of age.
AB  - Human 2D : 4D ratios (measures of the relative lengths of index and ring fingers)
      attract considerable research interest because they exhibit sexual dimorphism and
      are associated with various morphological, physiological and behavioural traits
      as well as sporting abilities and medical conditions. In an attempt to identify
      potential confounding factors in such studies, we have examined how relative and
      absolute digit lengths vary with gender and tested whether they are influenced by
      age, right-left asymmetry and hand preference. Participants between 4 and 60
      years of age were recruited from local educational sites. Hand photocopies and
      calliper measurement were used to obtain digit lengths. We employed linear
      regression analysis to examine the growth trajectories of individual digits,
      analyses of variance to isolate main and interaction effects of age, gender and
      hand preference, and paired t-tests to identify lateral asymmetries. Both digits
      exhibited biphasic growth with an early growth phase followed by a stable length
      phase. Digits in females attained their maximum length about 2.2 years (dextral
      subjects) or 5.1 years (sinistral subjects) earlier than those in males. Sexual
      dimorphism in 2D : 4D ratios was apparent by 4 years of age and age changes in
      ratios depended on gender, side and hand preference. Relative and absolute
      lengths displayed age, gender, hand-preference and age x gender interaction
      effects. Lengths tended to be greater in females in younger subjects and greater
      in males in older subjects. Ratios tended to be greater in sinistral subjects. In
      dextral subjects, significant lateral asymmetries in 2D lengths were seen at all
      ages but asymmetries in males and 4D lengths seemed to be age-dependent. We
      conclude that age, lateral asymmetry and hand preference are potential
      confounding factors and that future study designs should take account of these as
      well as other known confounders such as ethnicity, birth order, menstrual cycle
      phase and sexual preference.

PMID- 18624832
TI  - An in situ hybridization study of Runx2, Osterix, and Sox9 in the anlagen of
      mouse mandibular condylar cartilage in the early stages of embryogenesis.
AB  - Mandibular condylar cartilage is the best-studied mammalian secondary cartilage,
      differing from primary cartilage in that it originates from alkaline phosphatase
      positive progenitor cells. We previously demonstrated that three transcription
      factors related to bone and cartilage formation, namely Runx2, Osterix and Sox9,
      are simultaneously expressed in the anlage of mandibular condylar cartilage
      (condylar anlage) at embryonic day (E)14. In this study, expression of these
      transcription factors was investigated in the anlagen of mandibular bone
      (mandibular anlagen) from E11.0 to 14.0. Runx2 mRNA was first expressed in the
      mandibular anlage at E11.5. Osterix mRNA was first expressed at E12.0, and showed
      a different expression pattern from that of Runx2 from E12.5 to E14.0, confirming
      that Osterix acts downstream of Runx2. Sox9 mRNA was expressed in Meckel's
      cartilage and its anlagen throughout the experimental period, but not clearly in
      the mandibular anlagen until E13.0. At E13.5, the condylar anlage was
      morphologically identified at the posterior end of the mandibular anlage, and
      enhanced Sox9 mRNA expression was detected here. At this stage, Runx2 and Osterix
      mRNA were simultaneously detected in the condylar anlage. These results indicate
      that the Sox9 mRNA-expressing condylar anlage is derived from Runx2/Osterix mRNA
      expressing mandibular anlage, and that upregulation of Sox9 in this region acts
      as a trigger for subsequent condylar cartilage formation.

PMID- 18624834
TI  - Individual specialization in diet by a generalist marine predator reflects
      specialization in foraging behaviour.
AB  - 1. We studied chick diet in a known-age, sexed population of a long-lived
      seabird, the Brunnich's guillemot (Uria lomvia), over 15 years (N = 136; 1993
      2007) and attached time-depth-temperature recorders to examine foraging behaviour
      in multiple years (N = 36; 2004-07). 2. Adults showed specialization in prey fed
      to offspring, described by multiple indices calculated over 15 years: 27% of diet
      diversity was attributable to among-individual variation (within-individual
      component of total niche width = 0.73); average similarity of an individual's
      diet to the overall diet was 65% (mean proportional similarity between
      individuals and population = 0.65); diet was significantly more specialized than
      expected for 70% of individuals (mean likelihood = 0.53). These indices suggest
      higher specialization than the average for an across-taxa comparison of 49 taxa.
      3. Foraging behaviour varied along three axes: flight time, dive depth and dive
      shape. Individuals showed specialized individual foraging behaviour along each
      axis. These foraging strategies were reflected in the prey type delivered to
      their offspring and were maintained over scales of hours to years. 4.
      Specialization in foraging behaviour and diet was greater over short time spans
      (hours, days) than over long time spans (years). Regardless of sex or age, the
      main component of variation in foraging behaviour and chick diet was between
      individuals. 5. Plasma stable isotope values were similar across years, within a
      given individual, and variance was low relative to that expected from prey
      isotope values, suggesting adult diet specialized across years. Stable isotope
      values were similar among individuals that fed their nestlings similar prey items
      and there was no difference in trophic level between adults and chicks. We
      suggest that guillemots specialize on a single foraging strategy regardless of
      whether chick-provisioning and self-feeding. With little individual difference in
      body mass and physiology, specialization likely represents learning and
      memorizing optimal feeding locations and behaviours. 6. There was no difference
      in survival or reproductive success between specialists and generalists,
      suggesting these are largely equivalent strategies in terms of evolutionary
      fitness, presumably because different strategies were advantageous at different
      levels of prey abundance or predictability. The development of individual
      specialization may be an important precursor to diversification among seabirds.

PMID- 18624835
TI  - Clinical misleading: multiple bilateral nodules in an Ethiopian child.

PMID- 18624836
TI  - A clinical study comparing methyl aminolevulinate photodynamic therapy and
      surgery in small superficial basal cell carcinoma (8-20 mm), with a 12-month
      follow-up.
AB  - OBJECTIVE: To compare the efficacy and cosmetic outcome (CO) of photodynamic
      therapy with topical methyl aminolevulinate (MAL-PDT) with simple excision
      surgery for superficial basal cell carcinoma (sBCC) over a 1-year period.
      METHODS: In this multicentre, randomised, controlled, open study, patients were
      treated at baseline either with MAL-PDT (two sessions, 7 days apart, repeated 3
      months later if incomplete clinical response) or surgery (at baseline). Primary
      endpoints were clinical lesion response (CR) 3 months after last treatment and CO
      assessed by the investigator 12 months after last treatment. Secondary endpoints
      were CR at 12 months (i.e. recurrence) and CO assessed by the investigator at 3
      and 6 months and by the patient at 3, 6 and 12 months. RESULTS: Overall, 196
      patients were enrolled with 1.4 sBCC lesions on average per patient. Mean lesion
      count reduction at 3 months was 92.2% with MAL-PDT vs. 99.2% with surgery [per
      protocol (PP) population] confirming the non-inferiority hypothesis (95%
      confidence interval, -12.1, -1.9). A total of 92.2% lesions showed CR at 3 months
      with MAL-PDT vs. 99.2% with surgery (PP population). At 12 months, 9.3% lesions
      recurred with MAL-PDT and none with surgery. CO was statistically superior for
      MAL-PDT at all time points. At 12 months, 94.1% lesions treated with MAL-PDT had
      an excellent or good CO according to the investigator compared with 59.8% with
      surgery. This difference was confirmed with the patients' assessment. The
      proportion of excellent CO markedly improved with time with MAL-PDT unlike
      surgery. CONCLUSIONS: MAL-PDT offers a similarly high efficacy and a much better
      CO than simple excision surgery in the treatment of sBCC.

PMID- 18624837
TI  - A new c.2541delC mutation in the ATP2A2 gene in a Japanese patient with Darier's
      disease.

PMID- 18624838
TI  - Spider bite-induced pagetoid reticulosis?

PMID- 18624839
TI  - Palmoplantar psoriasis: a paradoxical adverse reaction induced by adalimumab.

PMID- 18624840
TI  - Neutrophilic dermatosis of the dorsal hands: an emerging entity.

PMID- 18624841
TI  - Management of superficial lymphangiectasias with laser: report of five patients.

PMID- 18624842
TI  - Isolated and concurrent prevalence of sensitization to transition metals in a
      Spanish population.
AB  - BACKGROUND: Positive patch test results to transition metals (nickel sulphate,
      palladium chloride, cobalt chloride and potassium dichromate) alone and in
      combinations with one another are well known. Numerous factors may play a role in
      isolated and concurrent sensitization to these allergens. OBJECTIVE: This study
      aims to describe the isolated and concurrent prevalence of sensitization to
      transition metals in a Spanish Dermatology Department, between 2000 and 2005, and
      to determine the prevalence of concomitant positive patch test reactions to
      different transitional metals. PATIENTS/METHODS: Patients (N= 1092) were tested
      with the standard series of our Allergic Contact Unity, using a standardized
      technique. Data from these patients were recorded on a computer entry form and
      analysed. Statistical analyses to evaluated associations of metal contact allergy
      were performed, and we evaluated the concordance among these associations of
      transition metals. RESULTS: Three hundred twenty (29.3%) patients reacted
      positively to nickel, 128 (11.7%) to palladium, 118 (10.8%) to cobalt and 82
      (7.5%) to chromium. The prevalence of positive reactions to metals was 32.4%. The
      association of palladium-nickel was the most frequent, with an acceptable
      concordance (k= 0.46). CONCLUSION: This study illustrates that concomitant
      positive patch test reactions to different transitional metals are frequently
      seen in patients with allergic contact dermatitis. Our results reflect the high
      prevalence of sensitization to nickel in Spain.

PMID- 18624843
TI  - Combination of short CAG and GGN repeats in the androgen receptor gene is
      associated with acne risk in North East China.
AB  - BACKGROUND: Acne vulgaris is one of the most common skin disorders, and androgen
      is known to play a key role in the development of acne. However, the exact
      genetic mechanism by which androgen receptor (AR) gene affects acne development
      is still unclear. OBJECTIVE: Our study aimed to investigate whether CAG and GGN
      polymorphism of the AR gene are associated with acne risk. PATIENTS AND METHODS:
      Two hundred thirty-eight patients and 207 controls were included in the study.
      The repeat lengths of the AR gene were determined by GeneScan analysis. RESULTS:
      Men with CAG < 23 and women with CAG < 24 had significant risk compared to those
      men with CAG > or = 23 [odds ratio (OR), 2.07; 95% confidence interval (95% CI),
      1.21-3.54] and women with CAG > or = 24 (OR, 2.05; 95% CI, 1.18-3.56). In males,
      GGN repeats, considered independently of the CAG repeat, have no significant
      effect on the acne risk; however, when combined with CAG repeats, the acne
      patients exhibited significantly higher frequency of the haplotypes CAG < 23/GGN
      < or = 23 (OR, 3.33; 95% CI, 1.10-10.07; P < 0.05) compared with the controls.
      CONCLUSION: Our results of this study strongly indicated that a shorter CAG
      repeat length and specific haplotypes of AR attributed to the risk of acne
      development and thus could serve as a susceptibility marker.

PMID- 18624844
TI  - A case of childhood flexural comedones.

PMID- 18624845
TI  - Atypical hyperpigmentation after acitretin and narrow-band ultraviolet B
      combination therapy.

PMID- 18624846
TI  - Annular leukocytoclastic vasculitis after the administration of an amlodipine
      generic.

PMID- 18624847
TI  - Balloon cell naevus.

PMID- 18624848
TI  - Lifetime prevalence fluctuations of common bacterial skin infections.

PMID- 18624849
TI  - Oral ulcerations caused by incorrect administration of desloratadine.

PMID- 18624850
TI  - Giant skin tags on unusual locations.

PMID- 18624851
TI  - Successful treatment of linear Darier's disease with topical adapalene.

PMID- 18624852
TI  - Neutrophilic dermatosis and sideroblastic anaemia: an unusual association.

PMID- 18624853
TI  - A review of photodynamic therapy in cutaneous leishmaniasis.
AB  - We present a review of six clinical studies investigating the use of photodynamic
      therapy (PDT) using porphyrin precursors for the treatment of Old World cutaneous
      leishmaniasis (CL). Thirty-nine patients with a total of 77 lesions received PDT
      using a range of treatment schedules following topical application of
      aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL). The tissue response to
      PDT is accompanied by a mild burning sensation, erythema and reversible hypo- and
      hyperpigmentation. Few mechanistic studies have addressed the principles
      underlying the use of PDT for CL. All six reviewed papers suggest that PDT with
      porphyrin precursors is relatively effective in treating CL. Data are still
      limited, and PDT cannot at this point be recommended in routine clinical
      practice. The mechanism of action of this promising therapeutic modality needs to
      investigated further and additional controlled trials need to be performed.

PMID- 18624854
TI  - Association between smoking and cutaneous ageing in a Brazilian population.
AB  - OBJECTIVE: This study aims to determine the relationship between smoking and
      cutaneous ageing. METHODS: A cross-sectional study was carried out on 301
      subjects (191 women and 110 men, aged between 25 and 86 years), of which 165 were
      non-smokers and 136 were smokers and ex-smokers. The association between tabagism
      and cutaneous ageing was controlled for other variables (solar exposure, age,
      skin phototype, sex, sunscreen use, alcohol consumption, coffee consumption,
      sports participation, body mass index, and history of relatives with precocious
      ageing). RESULTS: Analysis revealed that age, chronic solar exposure, skin
      phototype and tobacco load significantly contributed to the formation of facial
      wrinkles. The larger the tobacco load, the larger was the amount of facial
      wrinkling, with an odds ratio of 3.92 in 'heavy' smokers (> 40 packs/year) in
      relation to non-smokers. CONCLUSION: The results of this study point to smoking
      as one of the main factors involved in facial wrinkling. The relationship between
      smoking and cutaneous ageing is an important element in educational campaigns
      against tabagism.

PMID- 18624855
TI  - A chart review of patients with early-stage mycosis fungoides treated with
      psoralen plus ultraviolet A.

PMID- 18624856
TI  - Giant primary plantar melanoma.

PMID- 18624857
TI  - A double-blind, randomized trial of 0.05% betamethasone vs. topical
      catalase/dismutase superoxide in vitiligo.
AB  - BACKGROUND: Among all the topical immunomodulators, vitiligo's mainstay therapy
      includes topical corticosteroids. Many other non-immune theories have also been
      suggested for vitiligo's pathogenesis, but the role of oxidative stress has
      gained more importance in recent years. OBJECTIVE: To compare the effect of
      topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). STUDY
      DESIGN: Randomized, matched-paired, double-blind trial. SETTING: Dermatology
      Section, University of Antioquia, Medellin, Colombia. SUBJECTS: Patients (aged >
      18 years or between 12 and 18 years) with parent's informed consent, with stable
      or active bilateral vitiligo. INTERVENTION: Topical 0.05% betamethasone or C/DSO.
      METHODS: Two lesions similar to each other in size were chosen. All assessments
      were made by two blinded investigators, and photographs were subjected to
      morphometry analysis. MAIN OUTCOME: Skin repigmentation by digital morphometry.
      RESULTS: Twenty-five patients were enrolled in the study (21 women and 4 men).
      Mean age of participants was 40 years (range: 12-74 years). One patient on C/DSO
      experienced a mild local erythematous papular rash that self-resolved. At 4
      months of therapy, there was no statistical difference on the percentage of
      repigmentation between betamethasone and C/DSO (5.63% +/- 27.9 vs. 3.22% +/-
      25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of
      skin repigmentation increased to 18.5 +/- 93.14% with betamethasone and to 12.4
      +/- 59% with C/DSO, but again, we found no statistical differences (P = 0.79).
      DISCUSSION AND CONCLUSIONS: Few studies have described objective methods to
      evaluate repigmentation among vitiligo patients. Digital morphometry provides an
      objective assessment of repigmentation in vitiligo. Objective vitiligo
      repigmentation with topical C/DSO at 10 months is similar to topical 0.05%
      betamethasone. Although a mild adverse effect was related to the use of C/DSO,
      such finding was not severe enough to discontinue treatment.

PMID- 18624858
TI  - Vulvovaginal gingival syndrome and coeliac disease.

PMID- 18624859
TI  - Subcorneal pustular dermatosis with pathergy phenomenon in a patient with Crohn's
      disease.

PMID- 18624860
TI  - Completely regressed primary cutaneous malignant melanoma with metastases.

PMID- 18624861
TI  - Scanning electron microscopy of scutular tinea.

PMID- 18624862
TI  - Generalized cutaneous drug eruption due to strontium ranelate.

PMID- 18624863
TI  - Helium-neon laser and topical tacrolimus combination therapy: novel treatment
      option for vitiligo without additional photocarcinogenic risks.

PMID- 18624864
TI  - Low prescription rate for systemic treatments in the management of severe
      psoriasis vulgaris and psoriatic arthritis in dermatological practices in Berlin
      and Brandenburg, Germany: results from a patient registry.
AB  - BACKGROUND: Many treatment options are available for the management of psoriasis
      vulgaris. However, detailed data on prescription behaviour in Germany, especially
      with regard to the use of new treatment options (e.g. biologics) in private
      practices, are lacking. OBJECTIVE: To assess the treatment choices being made in
      the management of psoriasis vulgaris and psoriatic arthritis in private
      dermatological practices. METHODS: We established a patient registry that
      documented the treatment decisions taken during 4797 patient visits between
      January 2006 and September 2006 with regard to disease activity and concomitant
      psoriatic arthritis. RESULTS: Corticosteroids were the most frequently prescribed
      topical treatment, and methotrexate and fumaric acid esters were the most
      frequently prescribed systemic treatments. Biologics were prescribed in only 2%
      of patient visits. Systemic treatments were prescribed in only 31% of visits made
      by patients suffering from moderate to severe psoriasis (which was diagnosed in
      48% of all patient visits) and in only 58% of visits made by patients suffering
      from psoriatic arthritis (which was diagnosed in 12% of all patient visits).
      CONCLUSIONS: Anti-psoriatic treatment was too often limited to topical agents.
      The rather small percentage of patients with moderate to severe psoriasis or
      psoriatic arthritis who received systemic therapy indicates that the use of
      systemic treatments in our sample was too restrictive. Novel therapeutic options
      such as biologics were rarely used in private practices. New strategies to
      improve the quality of care provided to patients suffering from severe psoriasis
      are needed.

PMID- 18624865
TI  - A new non-syndromic type of familial carcinomas?

PMID- 18624867
TI  - Expression of activation inducer molecule (CD69) on CD3+CD8+ T lymphocytes in
      children with atopic dermatitis correlates with SCORAD but not with the age of
      patients.

PMID- 18624866
TI  - Effectiveness and safety of a prevention-of-flare-progression strategy with
      pimecrolimus cream 1% in the management of paediatric atopic dermatitis.
AB  - OBJECTIVE: This study was performed to investigate the efficacy and safety of a
      prevention-of-flare-progression strategy with pimecrolimus cream 1% in children
      and adolescents with atopic dermatitis (AD). METHODS: A 26-week multi-centre,
      randomized, double-blind, vehicle-controlled study was conducted in 521 patients
      aged 2-17 years, with a history of mild or moderate AD, who were clear/almost
      clear of disease before randomization to pimecrolimus cream 1% (n = 256) or
      vehicle cream (n = 265). Twice-daily treatment with study medication was started
      at the first signs and/or symptoms of recurring AD. If, despite the application
      of study medication for at least 3 days, AD worsened (as confirmed by the
      investigator), treatment with a moderately potent topical corticosteroid (TCS)
      was allowed in both groups. The primary efficacy end point was the number of days
      on study without TCS use for a flare. RESULTS: The mean number of TCS-free days
      was significantly higher (P < 0.0001) in the pimecrolimus cream 1% group (160.2
      days) than in the control group (137.7 days). On average, patients on
      pimecrolimus cream 1% experienced 50% fewer flares requiring TCSs (0.84) than
      patients on vehicle cream (1.68) (P < 0.0001). Patients on pimecrolimus cream 1%
      also had fewer unscheduled visits (87) than patients on vehicle cream (246).
      CONCLUSIONS: In children and adolescents with a history of mild or moderate AD
      but free/almost free of signs or symptoms of the disease, early treatment of
      subsequent AD exacerbations with pimecrolimus cream 1% prevented progression to
      flares requiring TCS, leading to fewer unscheduled visits and reducing
      corticosteroid exposure.

PMID- 18624868
TI  - Lipid profile in patients with psoriasis in Zahedan, south-east Iran.

PMID- 18624869
TI  - Multiple basal cell carcinomas arising on a thermal-burn scar. Successful
      treatment with photodynamic therapy.

PMID- 18624870
TI  - Facial actinic lichen planus following the Blaschko's lines: successful treatment
      with topical 0.1% pimecrolimus cream.

PMID- 18624871
TI  - Human papillomavirus detection in multiple large-cell acanthomas.

PMID- 18624872
TI  - Concurrence of erythema migrans and herpes simplex: first description of a highly
      unusual dual skin infection.

PMID- 18624873
TI  - A cross-sectional study of psychological morbidity in patients with acne,
      psoriasis and atopic dermatitis in specialist dermatology and general practices.
AB  - BACKGROUND: There is considerable evidence for an association of skin diseases
      with psychological morbidity. This relationship is best established for acne,
      psoriasis and atopic eczema. Previous studies have mostly been performed in
      specialist dermatological practice, and there is a lack of studies that include
      patients from general practice and a lack of controlled studies employing
      multivariate analysis. AIMS/OBJECTIVES: This study aims to examine the
      relationship of acne, psoriasis and atopic eczema with psychological morbidities
      in patients recruited from general practice as well as specialist dermatology
      practice. METHODS AND SUBJECTS: In this cross-sectional study, 108 patients from
      general and specialist dermatology practices with the three diseases had disease
      severity assessed and completed measures of minor psychological disturbance
      (General Health Questionnaire-12), anxiety and depression (Hospital Anxiety and
      Depression Scale), public self-consciousness and social anxiety (Fenigstein Self
      Consciousness Scale), and neuroticism and extraversion/introversion (Eysenck
      Personality Inventory). Demographic data were also collected, along with self
      ratings of disease severity. Control subjects were 96 patients without skin
      disease recruited from the same general practices as the subjects. RESULTS: On
      univariate analyses, patients with skin disease had higher levels of minor
      psychological disturbance, public self-consciousness and neuroticism than did
      controls. There were no differences in psychological measures between specialist
      and general practice patients or between patients with different skin diseases.
      On multivariate analyses, the significant differences did not persist.
      CONCLUSIONS: This study demonstrates confounding in the relationship of skin
      diseases with psychological morbidity. The complex relationship of skin disease
      and psychological morbidity should be re-examined.

PMID- 18624874
TI  - The advantage of establishing homogeneous patient groups: is it worth isolating
      'juvenile acne of the face'?
AB  - BACKGROUND: Acne is a highly heterogeneous disorder with respect to its regional
      involvement, demographics, lesion types and response to treatment. Homogeneous
      patient groups must therefore be created before measuring the severity of acne
      and interpreting the results of therapeutic trials. The individualization of
      'juvenile acne of the face' is a first step in this direction. METHODS: Based on
      textbooks, major reviews of acne and a 'Medline' literature search, we identified
      four key points to delineate sub groups of acne patients. RESULT: 'Juvenile acne
      of the face' is defined by four main clinical criteria: (1) age (from puberty to
      age 25 years), (2) site (face), (3) lesion type (polymorphous), (4) absence of a
      causal factor. Other subgroups of 'true' acne are listed with their distinctive
      characteristics. Non-acne follicular diseases (i.e. without sebum retention) are
      listed. DISCUSSION: We chose 'juvenile acne of the face' to define the first
      homogeneous group of patients because it is the most frequent form of acne and
      the target of most acne drugs. It has a sufficiently uniform prognosis to devise
      a functional and reproducible severity rating scale with the aim of facilitating
      the evaluation and comparison of therapeutic methods. CONCLUSION: The next step
      in our work will be to elaborate severity scales which are dedicated to a single
      type of acne.

PMID- 18624875
TI  - Pellagra: will we see it more frequently?

PMID- 18624876
TI  - Wolf's isotopic response: large annular polycyclic lichen planus occurring on
      healed lesions of dermatophytosis.

PMID- 18624877
TI  - Molluscum infestation of an epidermal cyst associated with focal hyperplasia of
      cyst wall.

PMID- 18624878
TI  - Detection of serum antibodies to human intracisternal A-type retroviral particles
      in chronic idiopathic urticaria.

PMID- 18624879
TI  - Burning mouth syndrome, oral parafunctions, and psychological profile in a
      longitudinal case study.

PMID- 18624880
TI  - Demonstration of gastrointestinal venous malformations in blue rubber bleb naevus
      syndrome using capsule endoscopy.

PMID- 18624881
TI  - Lack of association between the promoter polymorphisms at positions -238 and -308
      of the tumour necrosis factor alpha gene and acne vulgaris in Polish patients.

PMID- 18624882
TI  - Lichen planus runs along cutaneous superficial veins on the forearms: supravenous
      lichen planus?

PMID- 18624883
TI  - Sperm competition within a dominance hierarchy: investment in social status vs.
      investment in ejaculates.
AB  - There is increasing recognition that male-male competition can take many forms,
      but as yet the form is not predictable a priori. Many recent studies have focused
      attention on how males in disadvantaged mating roles compensate through sperm
      competition. However, mating systems in which subordinate males are
      reproductively suppressed, particularly through the stress of social
      interactions, may limit the ability of males to respond by increasing investment
      in sperm quality. We examined the interaction between social status and ejaculate
      tactics in Nauphoeta cinerea, a cockroach that has a mating system with well
      characterized dominance hierarchies. Both social experience with other males and
      social status influenced aspects of ejaculates. The stress of social interactions
      reduced the size of the ejaculate and number of sperm inseminated. In ejaculates
      formed prior to social experience, however, males that go on to become dominant
      inseminated more sperm than males that go on to become subordinate, suggesting
      innate differences among males. Our results show that though selection for
      increased success in sperm competition for subordinate males in a hierarchy can
      occur, both the traits and the way in which the balance between pre- and post
      copulatory strategies is negotiated will depend on specific details of the mating
      system. These details will include how the physiological effects of social
      interactions may limit selection through male-male competition.

PMID- 18624884
TI  - Sexual imprinting on continuous variation: do female zebra finches prefer or
      avoid unfamiliar sons of their foster parents?
AB  - Sexual imprinting on discrete variation that serves the identification of
      species, morphs or sexes is well documented. By contrast, sexual imprinting on
      continuous variation leading to individual differences in mating preferences
      within a single species, morph and sex has been studied only once (in humans). We
      measured female preferences in a captive population of wild-type zebra finches.
      Individual cross-fostering ensured that all subjects grew up with unrelated
      foster parents and nest mates. Females from two cohorts (N = 113) were given a
      simultaneous choice between (two or four) unfamiliar males, one of which was a
      genetic son of their foster parents (SFP). We found no significant overall
      preference for the SFP (combined effect size d = 0.14 +/- 0.15). Additionally, we
      tested if foster parent traits could potentially explain between-female variation
      in preferences. However, neither the effectiveness of cooperation between the
      parents nor male contribution to parental care affected female preferences for
      the son of the foster father. We conclude that at least in zebra finches sexual
      imprinting is not a major source of between-individual variation in mating
      preferences.

PMID- 18624885
TI  - Multiple parasites mediate balancing selection at two MHC class II genes in the
      fossorial water vole: insights from multivariate analyses and population
      genetics.
AB  - We investigated the factors mediating selection acting on two MHC class II genes
      (DQA and DRB) in water vole (Arvicola scherman) natural populations in the French
      Jura Mountains. Population genetics showed significant homogeneity in allelic
      frequencies at the DQA1 locus as opposed to neutral markers (nine
      microsatellites), indicating balancing selection acting on this gene. Moreover,
      almost exhaustive screening for parasites, including gastrointestinal helminths,
      brain coccidia and antibodies against viruses responsible for zoonoses, was
      carried out. We applied a co-inertia approach to the genetic and parasitological
      data sets to avoid statistical problems related to multiple testing. Two alleles,
      Arte-DRB-11 and Arte-DRB-15, displayed antagonistic associations with the
      nematode Trichuris arvicolae, revealing the potential parasite-mediated selection
      acting on DRB locus. Selection mechanisms acting on the two MHC class II genes
      thus appeared different. Moreover, overdominance as balancing selection mechanism
      was showed highly unlikely in this system.

PMID- 18624886
TI  - Toward evolutionary graphs with two sexes: a kin selection analysis of a sex
      allocation problem.
AB  - Evolutionary graphs are used to model the effects of spatial and social structure
      in social evolutionary problems (e.g. evolutionary games). Recent work has
      highlighted the fact that evolution on graphs can be understood using kin
      selection theory. This paper shows how one can use kin selection to study
      evolutionary graphs inhabited by a diploid sexual organism by means of a simple
      example. Specifically, we study the well-known sex allocation problem of how best
      to divide a fixed amount of effort between the production of sons on the one hand
      and the production of daughters on the other. Like many previous studies, we
      identify equal investment in sons and daughters as the only phenotype favoured by
      selection. Our analysis also highlights the advantages and disadvantages of
      applying kin selection to the study of evolutionary graphs.

PMID- 18624887
TI  - An insight into forensic document examiner expertise for discriminating between
      forged and disguised signatures.
AB  - It has previously been shown that forensic document examiners (FDEs) have
      expertise in providing opinions about whether questioned signatures are genuine
      or simulated. This study extends the exploration of FDE expertise by evaluating
      the performance of eight FDEs and 12 control subjects at identifying signatures
      as either forgeries or the disguised writing of a specimen provider. Subject eye
      movements and response times were recorded with a Tobii 1750 eye tracker during
      the signature evaluations. Using a penalty scoring system, FDEs performed
      significantly better than control subjects (t = 2.465, p = 0.024), with one FDE
      able to correctly call 13 of the 16 test stimuli (and three inconclusive calls).
      An analysis of eye movement search patterns by the subjects indicated that a very
      similar search strategy was employed by both groups, suggesting that visual
      inspection of signatures is mediated by a bottom up search strategy. However,
      FDEs spent greater than 50% longer to make a decision than the control group. The
      findings are suggestive that for some stimuli FDEs can discriminate between
      forgeries and disguises, and that this ability is due to a careful inspection and
      consideration of multiple features within a signature.

PMID- 18624888
TI  - Ossification of laryngeal structures as indicators of age.
AB  - As the role of forensic anthropologists expands to the medical examiner setting,
      their expertise is being applied beyond the traditional dry skeletal material. In
      such scenarios radiographic techniques can be applied when maceration is not
      appropriate. This study explores the use of radiographic analysis of laryngeal
      structures for age-at-death determination. Isolated human laryngeal structures (n
      = 104) from individuals between the ages of 15 and 89 were removed at autopsy and
      radiographically examined. The cricoid and individual regions of the thyroid
      cartilage were scored according to degree of ossification, and the relationship
      between age and degree of ossification statistically examined. A previously
      published study on age-determination from thyroid ossification by Cerny was
      assessed for accuracy. The results of the study indicate that although a
      consistent sequence in the ossification of laryngeal structures exists,
      variations in timing does not permit narrow age range estimates. Consequently the
      method presented by Cerny is inaccurate and should not be used in the forensic
      setting.

PMID- 18624889
TI  - Developmental validation of a Cannabis sativa STR multiplex system for forensic
      analysis.
AB  - A developmental validation study based on recommendations of the Scientific
      Working Group on DNA Analysis Methods (SWGDAM) was conducted on a multiplex
      system of 10 Cannabis sativa short tandem repeat loci. Amplification of the loci
      in four multiplex reactions was tested across DNA from dried root, stem, and leaf
      sources, and DNA from fresh, frozen, and dried leaf tissue with a template DNA
      range of 10.0-0.01 ng. The loci were amplified and scored consistently for all
      DNA sources when DNA template was in the range of 10.0-1.0 ng. Some allelic
      dropout and PCR failure occurred in reactions with lower template DNA amounts.
      Overall, amplification was best using 10.0 ng of template DNA from dried leaf
      tissue indicating that this is the optimal source material. Cross species
      amplification was observed in Humulus lupulus for three loci but there was no
      allelic overlap. This is the first study following SWGDAM validation guidelines
      to validate short tandem repeat markers for forensic use in plants.

PMID- 18624890
TI  - Death caused by a signal rocket--not an isolated case*.
AB  - Fatalities related to sporting events are predominantly caused by blunt force
      injuries especially due to the emotional involvement of crowd, but occasionally
      other types of trauma are reported as well. A case of very rare trauma caused by
      shooting with a hand-held parachute signal rocket during a football match is
      presented. A 17-year-old football fan sustained fatal injuries, a combination of
      mechanical trauma caused by rocket penetration, as well as extensive thermal
      burning of the thoracic viscera. Analysis of the event was based on autopsy
      findings and evidence produced by medicolegal and ballistic experts. Improper use
      of a hand-held signal rocket, designed for marine distress signals, may cause
      serious injuries either mechanically, due to explosion, or as a result of thermal
      discharge. In the reported case, pattern of injuries is discussed, and medical
      finding corroborated to other available evidence. The presented case is a
      reminder that the forensic pathologist should be informed accordingly on the type
      and features of weapon suspected to produce injury, to be able to understand
      traumatic changes, and look for potential presence of foreign bodies at
      postmortem examination.

PMID- 18624891
TI  - Estimating the timing of long bone fractures: correlation between the postmortem
      interval, bone moisture content, and blunt force trauma fracture
      characteristics*.
AB  - There is very limited knowledge about how long perimortem fracture
      characteristics persist into the postmortem interval (PMI). Therefore, in this
      study, 60 porcine long bones were exposed to natural taphonomic conditions and
      fractured with a steel bone breaking apparatus every 28 days throughout a 141-day
      period. Differences between macroscopic blunt force trauma fracture
      characteristics (fracture angle, surface morphology, and outline) were examined
      to determine if they varied over time or in relationship to bone moisture content
      (ash weight) and overall assessment. There are significant relationships between
      (1) PMI and percent ash weight (%AW), fracture surface, and fracture angle and
      (2) %AW and fracture surface and fracture angle. Bone moisture content correlates
      significantly with fracture morphology and other characteristics commonly used by
      forensic anthropologists to determine the timing of traumatic injuries. However,
      fracture characteristics normally associated with perimortem trauma can persist
      long into the PMI.

PMID- 18624892
TI  - Investigation into "normal" background DNA on adult necks: implications for DNA
      profiling of manual strangulation victims.
AB  - Others have investigated the role that DNA profiling could play as a method for
      identifying the perpetrator of manual strangulation. These studies have
      demonstrated that it is possible to collect offender DNA from the skin surface of
      a victim following physical contact. It is not known whether nonself biological
      material is normally present on the skin surface due to adventitious transfer
      occurring during innocent everyday interactions. To test the hypothesis that
      detectable amounts of nonself DNA are normally present on the skin surface of
      healthy adult individuals due to the adventitious transfer of DNA occurring
      during normal day-to-day social interactions, we designed an experiment in three
      phases. Phase 1 was used to deduce which DNA collection, extraction, and
      amplification methods were suited to investigating this question. During phase 2,
      the neck surface of 24 healthy adult volunteers was swabbed. DNA was extracted
      using the QIAamp DNA mini kit and amplified using the SGM Plus PCR amplification
      kit, using 28 PCR cycles. The work carried out during phase 3 involved a
      simulated assault to investigate primary and secondary transfer of DNA during
      physical contact. It was found that 23% of neck areas swabbed during phase 2 of
      this investigation showed nondonor alleles in the resulting DNA profile, with 5%
      of areas showing six or more nondonor alleles. The results of phase 3 showed that
      primary, secondary, and zero transfer of victim and/or offender DNA could be
      observed after physical contact and that alleles from an unknown source could
      still be detected in this more controlled experiment. The data presented in this
      paper demonstrate that DNA profiles generated after swabbing the skin surface of
      healthy adults can include components of an unknown source, present due to
      adventitious transfer. These components, if present in large quantities, have the
      potential to interfere with DNA profile interpretation of swabs taken for the
      investigation of physical assault by DNA profiling.

PMID- 18624893
TI  - Shopping cart injuries, entrapment, and childhood fatality.
AB  - Shopping carts may be associated with a variety of injuries, particularly in
      toddlers and young children. These usually relate to falls from carts or to tip
      overs. Injuries that are sustained include hematomas/contusions, abrasions,
      lacerations, fractures, and fingertip amputations. Fatal episodes are uncommon
      and are usually due to blunt craniocerebral trauma from falls. A case involving a
      19-month-old girl is reported who became entrapped when she inserted her head
      through the side frame of a cart that had been removed from a supermarket and
      left at her home address. Death was caused by neck compression. Although rare,
      the potential for lethal entrapment during unsupervised play means that the
      presence of stray shopping carts at private residences and in public places,
      including playgrounds and parks, is of concern. Strategies, such as coin
      deposits, should be encouraged to assist in the return of such carts to
      supermarkets.

PMID- 18624894
TI  - An examination of the sequence of intersecting lines using attenuated total
      reflectance-Fourier transform infrared spectral imaging.
AB  - In this study, the potential of attenuated total reflectance-Fourier transform
      infrared (ATR-FTIR) spectral imaging as a technique to determine the sequence of
      line crossings was examined. The technique was successful in determining the
      sequence of heterogeneous line intersections produced using ballpoint pens and
      laser printers. By imaging at characteristic frequencies, it was possible to form
      spectral images showing the spatial distribution of the materials. By examining
      the spectral images from the inks, it was possible to determine whether the ink
      was above or below the toner. In blind testing, ATR-FTIR spectral imaging results
      were directly compared to those obtained by eight experienced forensic document
      examiners using methods regularly employed in casework. ATR-FTIR spectral imaging
      was shown to achieve a 100% success rate in the blind tests, whereas some
      incorrect sequence determinations were made by the forensic document examiners
      when using traditional techniques. The technique was unable to image ink-jet
      printing, gel pens, roller ball pens, and felt-tip pens, and was also unable to
      determine the sequence of intersecting ballpoint pen lines.

PMID- 18624895
TI  - Unusual suicide with a chainsaw.
AB  - Described here is a case of suicide with the use of a chainsaw. A female
      suffering from schizophrenia committed suicide by an ingenious use of a chainsaw
      that resulted in the transection of her cervical spine and spinal cord. The
      findings of the resulting investigation are described and the mechanism of
      suicides with the use of a chainsaw is reviewed. A dry bone study was realized to
      determine the bone sections, the correlation between anatomic lesions and
      characteristics of chainsaw. The damage of organs and soft tissues is compared
      according to the kinds of chainsaw used.

PMID- 18624896
TI  - Clinical features and survival in Chinese patients with hepatitis B e antigen
      negative hepatitis B virus-related cirrhosis.
AB  - AIM: To compare the clinical features of hepatitis B e antigen (HBeAg)-negative
      and HBeAg-positive cirrhosis, and to define the survival and prognostic
      indicators of Chinese HBeAg-negative hepatitis B virus (HBV)-related cirrhosis.
      METHODS: Two hundred and seventeen patients with chronic hepatitis B cirrhosis
      were studied. Survival was calculated using the Kaplan-Meier method. Proportional
      hazards Cox regression procedure was used to identify independent predictors of
      survival. The relationship between HBV-DNA viral load and prognosis was also
      investigated. RESULTS: The mean follow-up time was 35 months (3-47 months). HBeAg
      negative liver cirrhosis patients comprised the greatest number of cirrhosis
      patients. Median alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) levels, median total leukocytes (WBC), hemoglobin (Hb), platelet (Plt) and
      HBV-DNA levels and the proportion of HBV-DNA > 10(5) copies/mL were lower in
      HBeAg-negative patients. There were fewer complications in patients treated with
      lamivudine than in other patients. Survival rates were significantly reduced in
      patients with HBeAg-negative cirrhosis (P = 0.0024). The baseline Child-Pugh
      scores and more than one decompensation during follow up were independent
      variables correlated with survival of HBeAg-negative liver cirrhosis patients (P
      = 0.006 and P = 0.001, respectively). The HBV-DNA viral load did not correlate
      with any complications or mortality rates of HBeAg-negative patients.
      CONCLUSIONS: The clinical features of HBeAg-negative and -positive liver
      cirrhosis differ. Survival was significantly reduced for Chinese patients with
      HBeAg-negative than -positive cirrhosis. Factors contributing to the prognosis
      were baseline Child-Pugh scores and the presence of more than one decompensation
      during follow up.

PMID- 18624897
TI  - Long-term outcome of endoscopic semiconductive diode laser irradiation therapy
      with injection of indocyanine green for early gastric cancer.
AB  - BACKGROUND AND AIM: Semiconductive laser irradiation has been used to treat early
      gastric cancer. However, the long-term follow up results have not been reported.
      The objective of the present study was to assess retrospectively the clinical
      usefulness of diode laser irradiation for early gastric cancer. METHODS: The
      subjects of this study were 13 patients (14 lesions) selected from 125 patients
      with early gastric cancer who were treated by endoscopy during the period from
      September 1995 to February 2003. The macroscopic tumor type was superficial type,
      including eight lesions of 0'-IIc and six lesions of 0'-IIa. Histological
      diagnoses were eight cases (nine lesions) of well-differentiated adenocarcinoma,
      three cases of moderately differentiated adenocarcinoma and two cases of poorly
      differentiated adenocarcinoma. After injection with indocyanine green solution (1
      mg/mL) into the submucosal layer, a semiconductive diode laser (30-40 W/s) was
      irradiated by the non-contacting method. RESULTS: The total amount of laser
      irradiation for 14 lesions was 9568.80 +/- 7197.01 J on average. There was no
      major complication. In the period up to December 2007, six patients survived and
      seven patients died. However, no-one died of progression of gastric cancer. The
      mean survival times of all patients, survivors and patients who died were 5 years
      2.8 months; 6 years 4.5 months; and 4 years 11.7 months, respectively.
      CONCLUSIONS: Early gastric cancer can be successfully treated by laser therapy
      with few complications and good prognosis. This method is expected to be most
      suitable and effective for elderly patients with serious underlying disease.

PMID- 18624898
TI  - Platelets contribute to the reduction of liver fibrosis in mice.
AB  - BACKGROUND AND AIM: Several recent studies have reported that liver cirrhosis
      (LC) can be ameliorated, but few adequate strategies are available against liver
      fibrosis. Although LC clinically shows thrombocytopenia and hypersplenism, the
      correlation with liver fibrosis and platelets remains unclear. The aim of the
      present study was to investigate the effect of platelets on liver fibrosis in
      mouse models. METHODS: To induce liver fibrosis, C57BL6 female mice were injected
      i.p. with 1 mL/kg carbon tetrachloride (CCl(4)) twice a week for 8 weeks.
      Thrombocytosis was achieved by giving thrombopoietin or splenectomy in addition
      to CCl(4) intoxication. At 8 weeks, whole blood and liver specimens were obtained
      for studies as follows: peripheral platelet counts, histopathological
      examination, hydroxyproline assay, immunostaining, quantification of mRNA
      expression, and microarray analysis. RESULTS: Thrombocytosis significantly
      reduced liver fibrosis and hydroxyproline content of liver tissues compared to
      mice with CCl(4) administration alone. Platelets suppressed increments in mRNA
      expression for transforming growth factor-beta, and increased matrix
      metalloproteinase-9 expression in the liver. Microarray analysis of the liver
      revealed that platelets upregulated gene expressions involved in cell
      proliferation compared to expression in mice with CCl(4) intoxication alone.
      Platelets also increased liver volume, proliferative cell nuclear antigen
      labeling index, and mitotic index in fibrotic mice. CONCLUSION: These results
      clearly show that platelets reduce liver fibrosis and promote liver regeneration,
      even under cirrhotic conditions. We, therefore, propose that platelets could
      offer a potent tool in the treatment of liver cirrhosis.

PMID- 18624899
TI  - Rapid hepatic fate specification of adipose-derived stem cells and their
      therapeutic potential for liver failure.
AB  - BACKGROUND AND AIM: Multipotential mesenchymal stem cells (MSC), present in many
      organs and tissues, represent an attractive tool for the establishment of a
      successful stem cell-based therapy in the field of regeneration medicine. Adipose
      tissue mesenchymal stem cells (AT-MSC), known as adipose-derived stem cells (ASC)
      are especially attractive in the context of future clinical applications because
      of their high accessibility and minimal invasiveness during the procedure to
      obtain them. The goal of the present study was to induce human ASC into
      functional hepatocytes in vitro within a very short period of time and to check
      their therapeutic potential in vivo. METHODS: In vitro generated ASC-derived
      hepatocytes were checked for hepatocyte-specific markers and functions.
      Afterwards, they were transplanted into nude mice with liver injury. Twenty-four
      hours after transplantation, biochemical parameters were evaluated in blood
      serum. RESULTS: We have shown here that ASC can be differentiated into
      hepatocytes within 13 days and can reach the functional properties of primary
      human hepatocytes. After transplantation into mice with acute liver failure, ASC
      derived hepatocytes can restore such liver functions as ammonia and purine
      metabolism. Markers of liver injury, alanine aminotransferase, aspartate
      aminotransferase, as well as ammonia, were decreased after ASC-derived hepatocyte
      transplantation. CONCLUSIONS: Our data highlight the properties of ASC as having
      a special affinity for hepatocyte differentiation in vitro and liver regeneration
      in vivo. Thus, ASC may be a superior choice for the establishment of a therapy
      for injured liver.

PMID- 18624900
TI  - Real-time polymerase chain reaction quantification of specific butyrate-producing
      bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with
      colorectal cancer.
AB  - BACKGROUND AND AIM: Bacterial metabolites produced in the bowel are potentially
      related to the genesis of colorectal cancer. Butyrate is protective against
      cancer, whereas hydrogen sulfide and oxygen free radicals can be toxic to the
      epithelium. The present study was designed to quantitate Eubacterium rectale,
      Faecalibacterium prausnitzii (both butyrate-producing bacteria), Desulfovibrio
      (sulfate-reducing bacteria), and Enterococcus faecalis (that produces
      extracellular superoxide) in the feces of patients with colorectal cancer.
      METHODS: DNA was extracted from feces of 20 patients with colorectal cancer, nine
      patients with upper gastrointestinal cancer and 17 healthy volunteers. Real-time
      polymerase chain reaction using primers aimed at 16S rDNA was used to quantitate
      the above bacterial species or genus, and this was expressed relative to
      amplification of universal sequences conserved among all bacteria. RESULTS:
      Levels of E. rectale and F. prausnitzii were decreased approximately fourfold (P
      = 0.0088 and 0.0028, respectively) in colorectal cancer patients compared to
      healthy control volunteers. Levels of Desulfovibrio were not significantly
      different between the three groups. E. faecalis populations were significantly
      higher in colorectal cancer patients compared to healthy volunteers (P = 0.0294).
      CONCLUSIONS: Butyrate producers were decreased and E. faecalis increased in the
      feces of colon cancer patients. These shifts in the colonic bacterial population
      could potentially lead to epithelial cell damage and increased turnover and may
      be a factor leading to colon cancer.

PMID- 18624901
TI  - Glycine N-methyltransferase is a favorable prognostic marker for human
      cholangiocarcinoma.
AB  - BACKGROUND AND AIM: Glycine N-methyltransferase (GNMT) is a susceptibility gene
      for human hepatocellular carcinoma (HCC). We previously reported that GNMT
      expression is diminished in HCC. Here we report our examination of GNMT
      expression patterns in cholangiocarcinoma and the relationship between its
      expression and prognosis. METHODS: We analyzed GNMT expression in tumor tissues
      from 33 cholangiocarcinoma patients (19 male) using immunohistochemistry (IHC)
      procedures with a GNMT monoclonal antibody (mAb 4-17). GNMT expression intensity
      and percentages were scored on a scale of 0 to 6. The association between GNMT
      expression and survival was analyzed using the Kaplan-Meier method, and
      prognostic factors were evaluated with a multivariate Cox proportional hazards
      regression model. RESULTS: High GNMT expression was found in epithelial cells of
      normal bile ducts. Six of 33 (18.2%) cholangiocarcinoma tissues had no GNMT
      expression. A statistically significant difference was noted in GNMT expression
      between male and female patients (68.4% vs 100%, P < 0.05). Compared to patients
      with GNMT expression scores > 3, the death hazard ratio for patients with GNMT
      scores <or= 3 was 3.68 (95% confidence interval = 1.17-11.59, P < 0.05).
      CONCLUSIONS: GNMT expression is a favorable prognosis predictor for
      cholangiocarcinoma.

PMID- 18624902
TI  - Does the varied use of NSAIDs explain the differences in the risk of myocardial
      infarction?
AB  - OBJECTIVE: To investigate the risk of myocardial infarction (MI) with diclofenac,
      ibuprofen and naproxen, taking into account the exposure patterns. DESIGN:
      Retrospective cohort study using the General Practice Research Database. Setting.
      UK primary care. Subjects. Patients aged 40+ years prescribed a traditional
      nonsteroidal anti-inflammatory drug (NSAID). The control cohort was frequency
      matched by disease risk score. INTERVENTION: Observational comparisons of MI
      rates. RESULTS: The study included 729,294 NSAID users and 443,047 controls. The
      relative rate (RR) for MI increased with cumulative and daily dose (RR = 1.05
      with 0-4 prior prescriptions and RR = 1.49 with 30+; RR = 1.05 with daily dose of
      < 1200 mg ibuprofen and RR = 1.96 with dose of > or = 2400 mg per day; for
      diclofenac, the RR was 1.13 with < 150 mg per day and 2.03 with > or = 300 mg per
      day). Diclofenac users had higher risks of MI (RR = 1.21) than ibuprofen (RR =
      1.04) or naproxen (RR = 1.03) users, but exposure varied between these drugs.
      Taking into account these exposure differences, it was found that the risk of MI
      was comparable in current and past long-term users. The patterns of hazard rates
      (i.e. absolute risks) of MI were similar in patients using ibuprofen, diclofenac
      or naproxen with similar history of NSAID use. There was no statistical
      difference between ibuprofen, diclofenac and ibuprofen in the linear trends for
      cumulative dose or daily dose. CONCLUSIONS: Long-term users of traditional NSAIDs
      have an increased risk of MI that is probably explained by the underlying disease
      severity. Most of the differences in MI risk between diclofenac, ibuprofen or
      naproxen may be explained by their varied use.

PMID- 18624903
TI  - Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary
      stent placement in patients on chronic oral anticoagulation.
AB  - OBJECTIVES: Optimal antithrombotic/anticoagulation therapy in patients on chronic
      oral anticoagulation (OAC) undergoing drug-eluting stent (DES) implantation is
      unknown. We investigated the efficacy and safety of two regimens of
      antithrombotic/anticoagulation therapy in patients who present for DES
      implantation whilst on OAC. METHODS: We included a series of 515 patients on OAC
      who underwent DES implantation between 2002 and 2007. Based on predefined
      clinical and echocardiographic criteria, 306 patients continued OAC (triple
      therapy) and 209 patients discontinued OAC (dual therapy) for the time they
      received antiplatelet therapy with clopidogrel and aspirin [stent-related
      antithrombotic treatment (SRAT)]. The primary end point was a composite of death,
      myocardial infarction, stent thrombosis or stroke. RESULTS: During SRAT the
      primary endpoint was observed in 13 patients in the group with triple therapy
      versus 15 patients in the group with dual therapy [Kaplan-Meier estimates 4.2%
      and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29-1.28; P =
      0.19]. At 2 years of follow-up, the primary endpoint was observed in 35 patients
      in the group with triple therapy versus 36 patients in the group with dual
      therapy (Kaplan-Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48-1.21; P
      = 0.25). Two-year incidence of major bleeding was 1.4% (n = 4, triple therapy)
      versus 3.1% (n = 6, dual therapy) (P = 0.34). CONCLUSIONS: In patients on chronic
      OAC undergoing DES implantation, clinical and echocardiographic criteria help to
      define postprocedural antithrombotic/anticoagulation therapy. Based on these
      criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a
      triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable
      safety and efficacy.

PMID- 18624904
TI  - The combined effect of albuminuria and inflammation on all-cause and
      cardiovascular mortality in nondiabetic persons.
AB  - OBJECTIVES AND DESIGN: Recent studies have shown that albuminuria accompanied by
      evidence of subclinical inflammation is more strongly associated with metabolic
      abnormalities and the development of atherosclerosis than albuminuria alone. The
      aim of this population-based prospective study was to examine the combined effect
      of albuminuria and inflammatory markers on all-cause and cardiovascular-mortality
      in nondiabetic individuals without macroalbuminuria. SUBJECTS AND METHODS:
      Urinary albumin and creatinine, some inflammatory markers (fibrinogen, white
      blood cell and monocyte count) and cardiovascular risk factors were measured in
      5702 persons in Tromso, Norway. Baseline data were collected in 1994-1995 and
      follow-up was through 2005. RESULTS: For a one standard deviation higher value of
      the log-transformed ratio between albumin and creatinine (ACR), the mortality
      rate ratio for all-cause mortality was 1.21 when adjusted for age, gender,
      established cardiovascular risk factors as well as fibrinogen and white blood
      cell count (P < 0.001). The corresponding mortality rate ratio for cardiovascular
      mortality was 1.24 (P < 0.001). Persons in the upper quartile of both ACR and
      either of the inflammatory markers had an age- and gender-adjusted all-cause and
      cardiovascular mortality rate that was four times that of subjects in the lowest
      quartiles (P < 0.001). CONCLUSION: ACR predicts all-cause and cardiovascular
      mortality in persons without known diabetes and macroalbuminuria. The mortality
      is especially high amongst individuals with elevated levels of both ACR and
      inflammatory markers.

PMID- 18624905
TI  - Thionamide-induced vasculitis: a case of alveolar haemorrhage secondary to
      propylthiouracil.

PMID- 18624906
TI  - Activation of beta-catenin signalling by GSK-3 inhibition increases p
      glycoprotein expression in brain endothelial cells.
AB  - This study investigates involvement of beta-catenin signalling in regulation of p
      glycoprotein (p-gp) expression in endothelial cells derived from brain
      vasculature. Pharmacological interventions that enhance or that block beta
      catenin signalling were applied to primary rat brain endothelial cells and to
      immortalized human brain endothelial cells, hCMEC/D3, nuclear translocation of
      beta-catenin being determined by immunocytochemistry and by western blot analysis
      to confirm effectiveness of the manipulations. Using the specific glycogen
      synthase kinase-3 (GSK-3) inhibitor 6-bromoindirubin-3'-oxime enhanced beta
      catenin and increased p-gp expression including activating the MDR1 promoter.
      These increases were accompanied by increases in p-gp-mediated efflux capability
      as observed from alterations in intracellular fluorescent calcein accumulation
      detected by flow cytometry. Similar increases in p-gp expression were noted with
      other GSK-3 inhibitors, i.e. 1-azakenpaullone or LiCl. Application of Wnt agonist
      [2-amino-4-(3,4-(methylenedioxy) benzylamino)-6-(3-methoxyphenyl)pyrimidine] also
      enhanced beta-catenin and increased transcript and protein levels of p-gp. By
      contrast, down-regulating the pathway using Dickkopf-1 or quercetin decreased p
      gp expression. Similar changes were observed with multidrug resistance protein 4
      and breast cancer resistance protein, both known to be present at the blood-brain
      barrier. These results suggest that regulation of p-gp and other multidrug efflux
      transporters in brain vasculature can be influenced by beta-catenin signalling.

PMID- 18624907
TI  - Glutamate mobilizes [Zn2+] through Ca2+ -dependent reactive oxygen species
      accumulation.
AB  - Liberation of zinc from intracellular stores contributes to oxidant-induced
      neuronal injury. However, little is known regarding how endogenous oxidant
      systems regulate intracellular free zinc ([Zn(2+)](i)). Here we simultaneously
      imaged [Ca(2+)](i) and [Zn(2+)](i) to study acute [Zn(2+)](i) changes in cultured
      rat forebrain neurons after glutamate receptor activation. Neurons were loaded
      with fura-2FF and FluoZin-3 to follow [Ca(2+)](i) and [Zn(2+)](i), respectively.
      Neurons treated with glutamate (100 microM) for 10 min gave large Ca(2+)
      responses that did not recover after termination of the glutamate stimulus.
      Glutamate also increased [Zn(2+)](i), however glutamate-induced [Zn(2+)](i)
      changes were completely dependent on Ca(2+) entry, appeared to arise entirely
      from internal stores, and were substantially reduced by co-application of the
      membrane-permeant chelator TPEN during the glutamate treatment. Pharmacological
      maneuvers revealed that a number of endogenous oxidant producing systems,
      including nitric oxide synthase, phospholipase A(2), and mitochondria all
      contributed to glutamate-induced [Zn(2+)](i) changes. We found no evidence that
      mitochondria buffered [Zn(2+)](i) during acute glutamate receptor activation. We
      conclude that glutamate-induced [Zn(2+)](i) transients are caused in part by
      [Ca(2+)](i)-induced reactive oxygen species that arises from both cytosolic and
      mitochondrial sources.

PMID- 18624909
TI  - Neurotrophin receptor homolog-2 regulates nerve growth factor signaling.
AB  - The neurotrophin receptor homolog (NRH2) is closely related to the p75
      neurotrophin receptor (p75NTR); however, its function and role in neurotrophin
      signaling are unclear. NRH2 does not bind to nerve growth factor (NGF), however,
      is able to form a receptor complex with tropomyosin-related kinase receptor A
      (TrkA) and to generate high-affinity NGF binding sites. Despite this, the
      mechanisms underpinning the interaction between NRH2 and TrkA remain unknown.
      Here, we identify that the intracellular domain of NRH2 is required to form an
      association with TrkA. Our data suggest extensive intracellular interaction
      between NRH2 and TrkA, as either the juxtamembrane or death domain regions of
      NRH2 are sufficient for interaction with TrkA. In addition, we demonstrate that
      TrkA signaling is dramatically influenced by the co-expression of NRH2.
      Importantly, NRH2 did not influence all downstream TrkA signaling pathways, but
      rather exerted a specific effect, enhancing src homology 2 domain-containing
      transforming protein (Shc) activation. Moreover, downstream of Shc, the co
      expression of NRH2 resulted in TrkA specifically modulating mitogen-activated
      protein kinase pathway activation, but not the phosphatidylinositol 3-kinase/Akt
      pathway. These results indicate that NRH2 utilizes intracellular mechanisms to
      not only regulate NGF binding to TrkA, but also specifically modulate TrkA
      receptor signaling, thus adding further layers of complexity and specificity to
      neurotrophin signaling.

PMID- 18624908
TI  - Transregulation of leukemia inhibitory [corrected] factor receptor expression and
      function by growth factors in neuroblastoma cells.
AB  - The cytokines that signal through the leukemia inhibitory factor (LIF) receptor
      are members of the neuropoietic cytokine family and have varied and numerous
      roles in the nervous system. In this report, we have determined the effects of
      growth factor stimulation on LIF receptor (LIFR) expression and signal
      transduction in the human neuroblastoma cell line NBFL. We show here that
      stimulation of NBFL cells with either epidermal growth factor or fibroblast
      growth factor decreases the level of LIFR in an extracellular signal-regulated
      kinase (Erk)1/2-dependent manner and that this down-regulation is due to an
      increase in the apparent rate of lysosomal LIFR degradation. Growth factor
      induced decreases in LIFR level inhibit both LIF-stimulated phosphorylation of
      signal transducers and activators of transcription 3 and LIFR-mediated gene
      induction. We also show that Ser1044 of LIFR, which we have previously shown to
      be phosphorylated by Erk1/2, is required for the inhibitory effects of growth
      factors. Neurons are exposed to varying combinations and concentrations of growth
      factors and cytokines that influence their growth, development, differentiation,
      and repair in vivo. These findings demonstrate that LIFR expression and signaling
      in neuroblastoma cells can be regulated by growth factors that are potent
      activators of the mitogen-activated protein kinase pathway, and thus illustrate a
      fundamental mechanism that underlies crosstalk between receptor tyrosine kinase
      and neuropoietic cytokine signaling pathways.

PMID- 18624910
TI  - Neuroactive steroids and GABAA receptor plasticity in the brain of the WAG/Rij
      rat, a model of absence epilepsy.
AB  - The role of neuroactive steroids and GABA(A) receptors in the generation of
      spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat
      model of absence epilepsy. The plasma, cerebrocortical, and thalamic
      concentrations of the progesterone metabolite 3alpha-hydroxy-5alpha-pregnan-20
      one (3alpha,5alpha-TH PROG) were increased in the WAG/Rij rat at 2 months of age
      compared with those in control (Wistar) rats. In contrast, the brain and
      peripheral levels of 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha
      TH DOC) did not differ between the two rat strains at this age. At 6 months of
      age, when absence epilepsy worsens in WAG/Rij rats, the plasma concentration of
      3alpha,5alpha-TH PROG remained high whereas that of 3alpha,5alpha-TH DOC had
      increased, the cerebrocortical levels of both 3alpha,5alpha-TH PROG and
      3alpha,5alpha-TH DOC had increased, and the thalamic concentrations of these
      metabolites had decreased. At 6 months of age the expression of the alpha(4) and
      delta subunits of the GABA(A) receptor in relay nuclei was increased. Finally,
      chronic stress induced by social isolation elicited a reduction in the amount of
      3alpha,5alpha-TH PROG in the thalamus of 2-month-old WAG/Rij rats that was
      associated with a reduction in the number and overall duration of SWDs at 6
      months of age. Absence epilepsy in the WAG/Rij rat is thus associated with
      changes in the abundance of neuroactive steroids and in the expression of
      specific GABA(A) receptor subunits in the thalamus, a brain area key to the
      pathophysiology of this condition.

PMID- 18624911
TI  - Long-term administration of cocaine or serotonin reuptake inhibitors results in
      anatomical and neurochemical changes in noradrenergic, dopaminergic, and
      serotonin pathways.
AB  - The catechol and indole pathways are important components underlying plasticity
      in the frontal cortex and basal ganglia. This study demonstrates that
      administering rats either cocaine or a selective serotonin (or 5
      hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) for 16 weeks results in
      reduced density of dopaminergic and noradrenergic terminals in the striatum and
      olfactory bulb, respectively, reflecting pruning of the terminal arbor of ventral
      midbrain dopaminergic and locus coeruleus noradrenergic neurones. In the striatum
      of cocaine-treated animals, basal dopamine levels, as well as cocaine-induced
      dopamine release, is diminished compared with controls. In contrast, serotonergic
      fibers, projecting from the raphe, sprout and have increased terminal density in
      the lateral septal nucleus and frontal cortex, following long-term cocaine or
      SSRI treatment. This is associated with elevated basal 5-HT and enhanced cocaine
      induced 5-HT release in the frontal cortex. The anatomical and neurochemical
      changes in serotonergic fibers following cocaine or SSRI treatment may be
      explained by attenuated 5-HT(1A) autoreceptor function in the raphe. This study
      demonstrates extensive plasticity in the morphology and neurochemistry of the
      catechol and indole pathways that contribute to drug-induced plasticity of the
      corticostriatal (and other) projections. Moreover, our data suggest that drug
      induced plastic adaptation is anatomically widespread and consequently, likely to
      have multiple and complex consequences.

PMID- 18624912
TI  - c-Abl is involved in high glucose-induced apoptosis in embryonic E12.5 cortical
      neural progenitor cells from the mouse brain.
AB  - Hyperglycemia causes direct apoptosis of neural progenitor cells (NPCs) in
      diabetic-induced neural tube defects in embryos. However, the underlying
      mechanisms are poorly understood. The present study is aimed to investigate the
      specific cellular proteins that may be involved in NPCs apoptosis as well as
      mechanisms by which the proteins regulate the oxidative stress-induced NPCs
      apoptosis. Our present results have shown that the expression of c-Abl was up
      regulated in NPCs exposed to high glucose in vitro. The increased c-Abl was
      localized mainly in the nucleus. High glucose also induced an increase in nuclear
      p53 protein levels and the p53-c-Abl complex in NPCs. Administration of reactive
      oxygen species scavengers decreased the protein level of c-Abl, p53 and NPCs
      apoptosis. Inhibition of c-Abl reduced NPCs apoptosis and the nuclear protein
      level of p53 in response to high glucose. These results demonstrate that c-Abl is
      involved in the reactive oxygen species-activated apoptotic pathways in NPCs
      apoptosis. Inhibition of c-Abl may protect NPCs against insults induced by high
      glucose via the modulation of NPCs apoptotic machinery.

PMID- 18624913
TI  - Gene transfer of PEDF attenuates ischemic brain damage in the rat middle cerebral
      artery occlusion model.
AB  - Pigment epithelium-derived factor (PEDF) is a 50-kDa glycoprotein that protects
      various types of cultured neurons against neurotoxic stimuli, but its precise
      role in the CNS is not fully understood. In this study, we used rats whose brains
      were transfected to over-express human PEDF in order to elucidate the
      neuroprotective effect of PEDF following transient middle cerebral artery
      occlusion (MCAO). A replication-defective adenoviral vector containing the human
      PEDF gene (Ad.PEDF) or E. colibeta-galactosidase (Ad.LacZ) was directly injected
      into the right striatum at 7 days prior to 70 min of MCAO in rats. Infarct volume
      and degree of edema of the Ad.PEDF-treated group were significantly reduced
      compared to the Ad.LacZ-treated group 24 h after MCAO. Degeneration of neurons,
      astrocytes, and oligodendrocytes caused by MCAO were attenuated by over
      expression of PEDF. The up-regulation of pro-inflammatory genes (TNFalpha, IL
      1beta, IL-6, COX-2, and iNOS) and water channel aquaporin 4 after MCAO was
      significantly reduced in Ad.PEDF-injected striatum. In conclusion, the results
      from this study provide the first in vivo evidence that PEDF is effective in
      protecting CNS neurons from ischemic insult, suggesting that PEDF may have a role
      as an endogenous neuroprotectant in the CNS.

PMID- 18624914
TI  - Mammalian cerebral metabolism and amino acid neurotransmission during
      hibernation.
AB  - This report demonstrates that during the torpor phase of hibernation, hamsters
      utilize (14)C and (13)C glucose in torpor-specific brain metabolic pathways.
      Microdialysis of (14)C glucose into the striatum rapidly induced a steady state
      labeling of extracellular fluid (ECF) lactate and labeling of tissue GABA,
      glutamate, glutamine, and alanine in ipsilateral and contralateral striata. The
      same tissue metabolites were labeled in cortex, hypothalamus, and brainstem after
      microdialysis of (14)C lactate into the lateral ventricle. Serine, aspartate,
      glycine, taurine, tyrosine, and methionine were not synthesized from glucose or
      lactate during torpor. ECF levels of amino and organic acids were low and
      unchanging during torpor and increased late during arousal to cenothermia.
      Labeled intracellular (14)C GABA and glutamate were not communicated to the
      striatal ECF or ventricular space during torpor. (13)C NMR demonstrated rapid
      formation of lactate and functional tricarboxylic acid cycles in GABAergic and
      glutamatergic neurons, and enrichment of glutamine and alanine after i.v. (13)C
      glucose. Large changes in tissue levels of amino acids occur prior to or during
      entrance into torpor but not during torpor. It is proposed that cerebral
      intracellular dehydration, the enlargement of ECF and the biochemistries
      associated with brain water homeostasis may have a role in regulating
      hibernation.

PMID- 18624915
TI  - Over-expression of Hsp27 does not influence disease in the mutant SOD1(G93A)
      mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a chronic, adult-onset neurodegenerative
      disorder characterized by the selective loss of upper and lower motor neurons,
      resulting in severe atrophy of muscles and death. Although the exact pathogenic
      mechanism of mutant superoxide dismutase 1 (SOD1) causing familial ALS is still
      elusive, toxic protein aggregation leading to insufficiency of chaperones is one
      of the main hypotheses. In this study, we investigated the effect of over
      expressing one of these chaperones, heat shock protein 27 (Hsp27), in ALS. Mice
      over-expressing the human, mutant SOD1(G93A) were crossed with mice that
      ubiquitously over-expressed human Hsp27. Even though the single transgenic hHsp27
      mice showed protection against spinal cord ischemia, the double transgenic
      SOD1(G93A)/hHsp27 mice did not live longer, and did not show a significant delay
      in the onset of disease compared to their SOD1(G93A) littermates. There was no
      protective effect of hHsp27 over-expression on the motor neurons and on the
      mutant SOD1 aggregates in the double transgenic SOD1(G93A)/hHsp27 mice. In
      conclusion, despite the protective action against acute motor neuron injury,
      Hsp27 alone is not sufficient to protect against the chronic motor neuron injury
      due to the presence of mutant SOD1.

PMID- 18624916
TI  - NCAM-derived peptides function as agonists for the fibroblast growth factor
      receptor.
AB  - The neural cell adhesion molecule (NCAM) directly interacts with the fibroblast
      growth factor receptor (FGFR). Both fibronectin type III (FN3) modules of NCAM
      are involved in this interaction. One of the NCAM-FGFR contact sites has been
      localized recently to the upper N-terminal part of the second NCAM FN3 module
      encompassing the F and G beta-strands and the interconnecting loop region. Here,
      we investigated whether any of the six putative strand-loop-strand regions in the
      first NCAM FN3 module are involved in FGFR interactions. Peptide sequences
      encompassing these regions, termed encamins, were synthesized and tested for
      their ability to bind and activate FGFR. Encamins localized to the N-terminal
      part of the first FN3 module did not interact with FGFR, whereas encamins
      localized to the C-terminal part, termed EncaminA, C and E, bound to and
      activated FGFR. The encamins induced FGFR-dependent neurite outgrowth, and
      EncaminC and E promoted neuronal survival and enhanced pre-synaptic function. In
      conclusion, the interaction between NCAM and FGFR probably involves multiple
      contact sites at an interface formed by the two NCAM FN3 modules and FGFR, and
      encamins could constitute important pharmacological tools for the study of
      specific functional aspects of NCAM, including neuroprotection and modulation of
      plasticity.

PMID- 18624917
TI  - Dietary flavonoid (-)epicatechin stimulates phosphatidylinositol 3-kinase
      dependent anti-oxidant response element activity and up-regulates glutathione in
      cortical astrocytes.
AB  - Flavonoids are plant-derived polyphenolic compounds with neuroprotective
      properties. Recent work suggests that, in addition to acting as hydrogen donors,
      they activate protective signalling pathways. The anti-oxidant response element
      (ARE) promotes the expression of protective proteins including those required for
      glutathione synthesis (xCT cystine antiporter, gamma-glutamylcysteine synthetase
      and glutathione synthase). The use of a luciferase reporter (ARE-luc) assay
      showed that the dietary flavan-3-ol (-)epicatechin activates this pathway in
      primary cortical astrocytes but not neurones. We also examined the distribution
      of NF-E2-related factor-2 (Nrf2), a key transcription factor in ARE-mediated gene
      expression. We found, using immunocytochemistry, that Nrf2 accumulated in the
      nuclei of astrocytes following exposure to tert-butylhydroquinone (100 microM)
      and (-)epicatechin (100 nM). (-)Epicatechin signalling via Nrf2 was inhibited by
      wortmannin implicating a phosphatidylinositol 3-kinase-dependent pathway.
      Finally, (-)epicatechin increased glutathione levels in astrocytes consistent
      with an up-regulation of ARE-mediated gene expression. Together, this suggests
      that flavonoids may be cytoprotective by increasing anti-oxidant gene expression.

PMID- 18624918
TI  - Neuromelanin can protect against iron-mediated oxidative damage in system
      modeling iron overload of brain aging and Parkinson's disease.
AB  - In Parkinson's disease (PD), dopamine neurons containing neuromelanin selectively
      degenerate. Neuromelanin binds iron and accumulates in aging. Iron accumulates in
      reactive form during aging, PD, and is involved in neurodegeneration. It is not
      clear how the interaction of neuromelanin and iron can be protective or toxic by
      modulating redox processes. Here, we investigated the interaction of neuromelanin
      from human substantia nigra with iron in the presence of ascorbic acid, dopamine,
      and hydrogen peroxide. We observed that neuromelanin blocks hydroxyl radical
      production by Fenton's reaction, in a dose-dependent manner. Neuromelanin also
      inhibited the iron-mediated oxidation of ascorbic acid, thus sparing this major
      antioxidant molecule in brain. The protective effect of neuromelanin on ascorbate
      oxidation occurs even in conditions of iron overload into neuromelanin. The
      blockade of iron into a stable iron-neuromelanin complex prevents dopamine
      oxidation, inhibiting the formation of neurotoxic dopamine quinones. The above
      processes occur intraneuronally in aging and PD, thus showing that neuromelanin
      is neuroprotective. The iron-neuromelanin complex is completely decomposed by
      hydrogen peroxide and its degradation rate increases with the amount of iron
      bound to neuromelanin. This occurs in PD when extraneuronal iron-neuromelanin is
      phagocytosed by microglia and iron-neuromelanin degradation releases
      reactive/toxic iron.

PMID- 18624919
TI  - Effects of advanced glycation end products-inductor glyoxal and hydrogen peroxide
      as oxidative stress factors on rat retinal organ cultures and neuroprotection by
      UK-14,304.
AB  - Retinal ganglion cell degeneration is supposed to be mediated by reactive oxygen
      species (ROS) and advanced glycation end products (AGEs). The alpha2-adrenergic
      agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (brimonidine;
      UK-14,304), is said to exert a neuroprotective effect. To investigate these
      mechanisms in detail, we exposed rat whole mounts to glyoxal or H(2)O(2) and
      treated them with either UK-14,304 alone or additionally with the
      phosphatidylinositide 3 kinase (PI3) kinase inhibitor, 2-(4-Morpholinyl)-8-phenyl
      4H-1-benzopyran-4-one (Ly 294002). The accumulation of Nepsilon-[carboxymethyl]
      lysine (CML) was assessed immunohistochemically and changes in intracellular pH
      (pHi), mitochondrial transmembrane potential (MTMP) and ROS production in cell
      bodies of multipolar ganglion cell layer were studied by intravital fluorescence
      microscopy and confocal laser scanning microscopy. Ultrastructural changes in
      mitochondria of multipolar ganglion cell layer cell bodies were determined by
      transmission electron microscopy. We found that glyoxal and H(2)O(2) increased
      accumulation of CML-modified proteins and ROS production and decreased pHi and
      MTMP in cell bodies of multipolar ganglion cell layer. UK-14,304 could prevent
      production of ROS, accumulation of CML-modified proteins, ameliorate
      acidification, preserve MTMP and attenuate ultrastructural damages of ganglion
      cell mitochondria. Ly 294002 reversed the UK-14,304-mediated attenuation of CML
      and ROS production. We conclude that the protective effects of UK-14,304 seem
      partly to be mediated by PI3 kinase-dependent pathways.

PMID- 18624921
TI  - Identification and characterization of a novel, shorter isoform of the small
      conductance Ca2+ -activated K+ channel SK2.
AB  - Throughout the CNS, small conductance Ca(2+)-activated potassium (SK) channels
      modulate firing frequency and neuronal excitability. We have identified a novel,
      shorter isoform of standard SK2 (SK2-std) in mouse brain which we named SK2-sh.
      SK2-sh is alternatively spliced at exon 3 and therefore lacks 140 amino acids,
      which include transmembrane domains S3, S4 and S5, compared with SK2-std. Western
      blot analysis of mouse hippocampal tissue revealed a 47 kDa protein product as
      predicted for SK2-sh along with a 64 kDa band representing the standard SK2
      isoform. Electrophysiological recordings from transiently expressed SK2-sh
      revealed no functional channel activity or interaction with SK2-std. With the
      help of real-time PCR, we found significantly higher expression levels of SK2-sh
      mRNA in cortical tissue from AD cases when compared with age-matched controls. A
      similar increase in SK2-sh expression was induced in cortical neurons from mice
      by cytokine exposure. Substantial clinical evidence suggests that excess
      cytokines are centrally involved in the pathogenesis of Alzheimer's disease.
      Thus, SK2-sh as a downstream target of cytokines, provide a promising target for
      additional investigation regarding potential therapeutic intervention.

PMID- 18624920
TI  - Complement C3 and C4 expression in C1q sufficient and deficient mouse models of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease resulting in progressive
      cognitive decline. Amyloid plaque deposits consisting specifically of beta
      amyloid peptides that have formed fibrils displaying beta-pleated sheet
      conformation are associated with activated microglia and astrocytes, are
      colocalized with C1q and other complement activation products, and appear at the
      time of cognitive decline in AD. Amyloid precursor protein (APP) transgenic mouse
      models of AD that lack the ability to activate the classical complement pathway
      display less neuropathology than do the APPQ+/+ mice, consistent with the
      hypothesis that complement activation and the resultant inflammation may play a
      role in the pathogenesis of AD. Further investigation of the presence of
      complement proteins C3 and C4 in the brain of these mice demonstrate that both C3
      and C4 deposition increase with age in APPQ+/+ transgenic mice, as expected with
      the age-dependent increase in fibrillar beta-amyloid deposition. In addition,
      while C4 is predominantly localized on the plaques and/or associated with
      oligodendrocytes in APPQ+/+ mice, little C4 is detected in APPQ-/- brains
      consistent with a lack of classical complement pathway activation because of the
      absence of C1q in these mice. In contrast, plaque and cell associated C3
      immunoreactivity is seen in both animal models and, surprisingly, is higher in
      APPQ-/- than in APPQ+/+ mice, providing evidence for alternative pathway
      activation. The unexpected increase in C3 levels in the APPQ-/- mice coincident
      with decreased neuropathology provides support for the hypothesis that complement
      can mediate protective events as well as detrimental events in this disease.
      Finally, induced expression of C3 in a subset of astrocytes suggests the
      existence of differential activation states of these cells.

PMID- 18624922
TI  - Modulation of the neuronal response to ischaemia by somatostatin analogues in
      wild-type and knock-out mouse retinas.
AB  - Somatostatin acts at five G protein-coupled receptors, sst(1)-sst(5). In mouse
      ischaemic retinas, the over-expression of sst(2) (as in sst(1) knock-out mice)
      results in the reduction of cell death and glutamate release. In this study, we
      reported that, in wild-type retinas, somatostatin, the multireceptor ligand
      pasireotide and the sst(2) agonist octreotide decreased ischaemia-induced cell
      death and that octreotide also decreased glutamate release. In contrast, cell
      death was increased by blocking sst(2) with cyanamide. In sst(2) over-expressing
      ischaemic retinas, somatostatin analogues increased cell death, and octreotide
      also increased glutamate release. To explain this reversal of the anti-ischaemic
      effect of somatostatin agonists in the presence of sst(2) over-expression, we
      tested sst(2) desensitisation because of internalisation or altered receptor
      function. We observed that (i) sst(2) was not internalised, (ii) among G protein
      coupled receptor kinases (GRKs) and regulators of G protein signalling (RGSs),
      GRK1 and RGS1 expression increased following ischaemia, (iii) both GRK1 and RGS1
      were down-regulated by octreotide in wild-type ischaemic retinas, (iv) octreotide
      down-regulated GRK1 but not RGS1 in sst(2) over-expressing ischaemic retinas.
      These results demonstrate that sst(2) activation protects against retinal
      ischaemia. However, in the presence of sst(2) over-expression sst(2) is
      functionally desensitised by agonists, possibly because of sustained RGS1 levels.

PMID- 18624923
TI  - Premature centromere division of the X chromosome in neurons in Alzheimer's
      disease.
AB  - Premature centromere division (PCD) represents a loss of control over the
      sequential separation and segregation of chromosome centromeres. Although first
      described in aging women, PCD on the X chromosome (PCD,X) is markedly elevated in
      peripheral blood lymphocytes of individuals suffering from Alzheimer disease
      (AD). The present study evaluated PCD,X, using a fluorescent in situ
      hybridization method, in interphase nuclei of frontal cerebral cortex neurons
      from sporadic AD patients and age-matched controls. The average frequency of
      PCD,X in AD patients (8.60 +/- 1.20%) was almost three times higher (p < 0.01)
      than in the control group (2.96 +/- 1.20). However, consistent with previous
      studies, no mitotic cells were found in neurons in either AD or control brain,
      suggesting an intrinsic inability of post-mitotic neurons to divide. In view of
      the fact that it has been well-documented that neurons in AD can re-enter into
      the cell division cycle, the findings presented here of increased PCD advance the
      hypothesis that deregulation of the cell cycle may contribute to neuronal
      degeneration and subsequent cognitive deficits in AD.

PMID- 18624924
TI  - Negative regulation of neurogenesis and spatial memory by NR2B-containing NMDA
      receptors.
AB  - Several lines of evidence suggest involvement of NMDA receptors (NMDARs) in the
      regulation of neurogenesis in adults and the formation of spatial memory.
      Functional properties of NMDARs are strongly influenced by the type of NR2
      subunits incorporated. In adult forebrain regions such as the hippocampus and
      cortex, only NR2A and NR2B subunits are available to form the receptor complex
      with NR1 subunit. NR2B is predominant NR2 subunit in any of rat or human neural
      stem cells (NSCs). Thus, we suppose that NR2B-containing NMDAR should be critical
      in regulating adult neurogenesis, and thereby playing a role in the formation of
      spatial memory. In the cultured NSCs derived from the embryonic brain of rats,
      NR2B subunit-specific NMDAR antagonist Ro25-6981 increased cell proliferation,
      whereas MK-801, non-selective open-channel blocker of NMDARs, inhibited cell
      proliferation. Blockade of NR2B-containing NMDAR stimulated neurogenesis in the
      adult hippocampus and facilitated the formation of spatial memory. The enhanced
      spatial memory dropped back to base level when the NR2B antagonist-induced
      neurogenesis was neutralized by 3'-azido-deoxythymidine, a telomerase inhibitor.
      In addition, blockade of NR2B inhibited neuronal nitric oxide synthase (nNOS)
      enzymatic activity. In null mutant mice lacking nNOS gene (nNOS-/-), the effects
      of NR2B antagonist on neurogenesis disappeared. Moreover, nitric oxide donor
      DETA/NONOate attenuated and nNOS inhibitor 7-nitroindazole enhanced the effect of
      Ro 25-6981 on NSCs proliferation. Our findings suggest that NR2B-containing NMDAR
      subtypes negatively regulate neurogenesis in the adult hippocampus by activating
      nNOS activity and thereby hinder the formation of spatial memory.

PMID- 18624925
TI  - Activation of microglia with zymosan promotes excitatory amino acid release via
      volume-regulated anion channels: the role of NADPH oxidases.
AB  - Microglia are the resident immune cells of the CNS, which are important for
      preserving neural tissue functions, but may also contribute to neurodegeneration.
      Activation of these cells in infection, inflammation, or trauma leads to the
      release of various toxic molecules, including reactive oxygen species (ROS) and
      the excitatory amino acid glutamate. In this study, we used an electrophysiologic
      approach and a D-[(3)H]aspartate (glutamate) release assay to explore the ROS
      dependent regulation of glutamate-permeable volume-regulated anion channels
      (VRACs). Exposure of rat microglia to hypo-osmotic media stimulated Cl(-)
      currents and D-[(3)H]aspartate release, both of which were inhibited by the
      selective VRAC blocker, DCPIB. Exogenously applied H(2)O(2) potently increased
      swelling-activated glutamate release. Stimulation of microglia with zymosan
      triggered production of endogenous ROS and strongly enhanced glutamate release
      via VRAC in swollen cells. The effects of zymosan were attenuated by the ROS
      scavenger, MnTMPyP, and by two inhibitors of NADPH oxidase (NOX),
      diphenyliodonium and thioridazine. However, zymosan-stimulated glutamate release
      was insensitive to other NOX blockers, apocynin and HEBSF. This pharmacologic
      profile pointed to the potential involvement of apocynin-insensitive NOX4. Using
      RT-PCR we confirmed that NOX4 is expressed in rat microglial cells along with
      NOX1 and NOX2. To check for potential involvement of phagocytic NOX2, we
      stimulated this isoform using protein kinase C (PKC) activator, phorbol 12
      myristate 13-acetate or inhibited it with the broad spectrum PKC blocker, Go6983.
      Both agents potently modulated endogenous ROS production by NOX2 but not VRAC
      activity. Taken together, these data suggest that the anion channel VRAC may
      contribute to microglial glutamate release and that its activity is regulated by
      endogenous ROS originating from NOX4.

PMID- 18624926
TI  - Development of an immortalised, post-pubertal gonadotrophin-releasing hormone
      neuronal cell line.
AB  - Gonadotrophin-releasing hormone (GnRH) is important in reproduction, although
      some of the mechanisms for its synthesis and release remain elusive. Progress in
      understanding the GnRH neurone has been hampered by the limited number and
      diffuse distribution of the neurone in the mammalian brain. Several stable GnRH
      expressing cell lines have been developed using in vivo expression of the simian
      virus 40 T Antigen (TAg), and they have been helpful for the study of gene
      expression and neuronal function. However, expression of an immortalising gene
      may interfere with normal cellular function. We developed a novel GnRH-secreting
      cell line transgenic mouse model suitable for targeted transformation in post
      pubertal mice using a tetracycline-regulated TAg transgene. This clonal cell
      line, GRT, expresses neuronal markers and GnRH. GRT cells grown in medium
      containing tetracycline-free serum express increasing mRNA levels of GnRH
      associated with declining levels of TAg expression. The novelty and ultimately
      the usefulness of this cell line is that TAg expression, which could affect the
      GnRH neuronal phenotype, can be regulated by tetracycline.

PMID- 18624927
TI  - Direct inhibitory effect of glucocorticoids on corticotrophin-releasing hormone
      gene expression in neurones of the paraventricular nucleus in rat hypothalamic
      organotypic cultures.
AB  - Corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory
      neurones of hypothalamic paraventricular nucleus governs neuroendocrine stress
      cascade and is the major target of the negative feedback effect of
      corticosteroids. To assess whether glucocorticoids exert their inhibitory effect
      on CRH expression directly on parvocellular neurones or indirectly through a
      complex neuronal circuit, we examined the effect of corticosterone (CORT) and
      dexamethasone (DEX) on CRH mRNA levels in slice explant cultures of the rat
      hypothalamus. Organotypic slice cultures were prepared from 6 days old rat pups
      and maintained in vitro for 14 days. CRH mRNA expression was measured by in situ
      hybridisation histochemistry. Under basal conditions, CRH mRNA expressing cells
      were exclusively revealed in the paraventricular region along the third
      ventricle. Inhibition of action potential spike activity by tetrodotoxin (TTX, 1
      microm) reduced CRH mRNA signal in the organotypic cultures. CORT (500 nm) or DEX
      (50 nm) treatment for 24 h significantly inhibited CRH expression in the
      parvocellular neurones and this effect of corticosteroids was not affected
      following blockade of voltage dependent sodium channels by TTX. Forskolin
      stimulated CRH mRNA levels in the paraventricular nucleus were also inhibited by
      CORT or DEX in the presence and in the absence of TTX. These studies identify
      paraventricular CRH neurones as direct target of corticosteroid feedback. Type II
      corticosteroid receptor agonists act directly on paraventricular neurones to
      inhibit basal and forskolin-induced CRH mRNA expression in explant cultures of
      the rat hypothalamus.

PMID- 18624928
TI  - Regulation of cocaine- and amphetamine-regulated transcript-synthesising neurons
      of the hypothalamic paraventricular nucleus by endotoxin; implications for
      lipopolysaccharide-induced regulation of energy homeostasis.
AB  - Infectious diseases and the administration of bacterial lipopolysaccharide (LPS)
      result in decreased food intake and increased energy expenditure. Because the
      hypothalamic paraventricular nucleus (PVN) has pivotal roles in the regulation of
      energy homeostasis and expresses an anorexic peptide, cocaine- and amphetamine
      regulated transcript (CART), we hypothesised that increased CART synthesis in
      this nucleus may contribute to LPS-induced changes in energy homeostasis.
      Therefore, we studied the effects of intraperitoneal administration of LPS on
      CART gene expression in the PVN by semiquantitative in situ hybridisation. LPS
      caused a rapid increase in CART mRNA levels in the PVN. One hour after treatment,
      the density of silver grains was increased by three-fold in the PVN, and remained
      elevated 3 h after treatment. Because the dorsal vagal complex, an important
      vegetative centre in the brainstem, is heavily innervated by CART-containing
      axons, we determined whether the retrograde tracer, cholera toxin B subunit
      (CTB), accumulates in CART neurons in the PVN following stereotaxic injection of
      the tracer into the dorsal vagal complex. One week after injection, CTB
      accumulated in CART neurons in the ventral, medial, and lateral parvocellular
      subdivisions of the PVN. In addition, LPS administration induced c-fos expression
      in a population of CART neurons in the PVN that project to the dorsal vagal
      complex. These data indicate that increased CART gene expression in neurons of
      PVN may contribute to LPS-induced anorexia, and suggest that this action may be
      mediated, at least in part, through a PVN-dorsal vagal complex pathway.

PMID- 18624929
TI  - Endocannabinoids and the neurochemistry of gluttony.
AB  - Cannabis exerts its actions by mimicking 'endocannabinoid' neuromodulators at CB1
      receptors in brain and peripheral tissues. The endocannabinoids both stimulate
      appetite by increasing food craving and enjoyment and promote the deposition of
      energy as fat in adipose tissues. These findings have raised the possibility of
      CB1 antagonists as a novel class of anti-obesity agents.

PMID- 18624930
TI  - Expression of neurotensin and its receptors in pituitary adenomas.
AB  - The neurotensin (NT) produced in the hypothalamus and in pituitary gonadotrophs
      and thyrotrophs participates in neuroendocrine regulation. Recently, the
      involvement of this peptide in normal and neoplastic cell proliferation has been
      postulated. In the present study, we evaluated the expression of NT and its
      receptors (NTR1, 2 and 3) in a series of 50 pituitary adenomas [11 growth hormone
      (GH)-, eight prolactin (PRL)-, four adrenocorticotrophic hormone (ACTH)- and 27
      nonfunctioning adenomas]. NT mRNA expression was significantly higher in
      functioning compared to nonfunctioning adenomas and with normal pituitary.
      Nonfunctioning pituitary adenomas showed lower expression of NT mRNA than normal
      pituitary. In the immunohistochemical study of functioning adenomas, NT was
      colocalised with GH, PRL and ACTH secreting cells. In nonfunctioning adenomas,
      the NT immunoreactivity intensity was variable among the samples. NTR3 mRNA
      expression was observed in all examined samples and was higher in the adenomas,
      both functioning and nonfunctioning, compared to normal pituitary. By contrast,
      NTR1 and NTR2 mRNA were not detected in either pituitary adenomas or normal
      tissue. The higher expression of NTR3, as well as the expression of NT by
      tumoural corticotrophs, lactotrophs and somatotrophs, which are cells types that
      do not express this peptide in the normal pituitary, suggests that NT autocrine
      and/or paracrine stimulation mediated by NTR3 may be a mechanism associated with
      the tumourigenesis of functioning adenomas.

PMID- 18624931
TI  - CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and
      invasion of oral squamous cell carcinoma cells.
AB  - BACKGROUND: Oral squamous cell carcinomas (OSCCs) are characterized by a high
      degree of local invasion and a high rate of metastases to cervical lymph nodes.
      Downregulation of CXCR-4 by siRNA inhibits invasion and growth of breast and
      colon cancer cells. However, there have been no reports on the downregulation of
      CXCR-4 by small interfering RNA (siRNA) in oral cancer cells. METHODS: We
      generated two stable CXCR-4-knockdown clones (KBsi and KOSCC-25Bsi) from the KB
      and KOSCC-25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell
      proliferation assays were used to investigate the effect of CXCR-4 downregulation
      on cell proliferation and invasiveness in KBsi and KOSCC-25Bsi.
      Immunohistochemistry was performed to evaluate the correlation between CXCR-4
      expression and proliferation in 26 OSCC tissue samples. RESULTS: CXCR4-knockdown
      OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to
      29.5% of the vector-infected controls, and KOSCC-25Bsi decreased to 38.1% of the
      control vector-infected cells (P < 0.05). The CXCR4-knockdown OSCC cells grew
      significantly slower than the vector-infected control cells. KBsi and KOSCC-25Bsi
      cells proliferated at 69.5% and 71.7%, respectively, of the rate of control
      vector-infected cells (P < 0.05). CXCR-4-positive group had significantly higher
      PCNA labeling index than CXCR-4-negative group in OSCC tissue samples.
      CONCLUSION: These results suggest that the downregulation of CXCR-4 induces anti
      proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful
      target molecule for the treatment of OSCC.

PMID- 18624932
TI  - The reported prevalence of oral lichen planus: a review and critique.
AB  - OBJECTIVE: To examine all studies reporting prevalences of oral lichen planus
      (OLP) for epidemiological validity and to extract prevalence data from the valid
      papers. DESIGN: Computer based literature searches were carried out using the
      MeSH headings 'lichen planus, oral and (prevalence or incidence)' and were
      supplemented by manual searching. MAIN OUTCOME MEASURES: Each paper was examined
      for five criteria: clinic-based or population study, adequate demographic
      description (by sex and age group) of the population, adequate demographic
      description of the sample (if the population was sampled), adequate demographic
      description of the OLP cases identified, and histological confirmation of the
      clinical diagnosis. RESULTS: Forty-five relevant papers were identified, 21
      clinic-based and 24 population studies. All but one of the population studies was
      deficient. One study, while having some defects, was probably sufficiently valid
      to permit the findings to be regarded as useful. An overall age-standardized
      prevalence of 1.27% (0.96% in men and 1.57% in women) can be calculated from this
      study. CONCLUSIONS: There appears to be only one usable prevalence study of OLP.
      Other large-scale studies are required in other populations. Such studies need to
      distinguish between OLP and lichenoid reactions.

PMID- 18624933
TI  - Betel quid chewing, oral cancer and other oral mucosal diseases in Vietnam: a
      review.
AB  - BACKGROUND: Betel quid chewing (BQC) in Vietnam is still prevalent, however, no
      detailed information about its association with oral cancer and pre-cancer are
      available in the English literature. Respective online searches (PubMed, Medline)
      were negative. METHODS: Relevant publications in Vietnamese were collected by the
      authors and translated. Visits to cancer centres and institutes of odontology (Ho
      Chi Minh City, Hanoi) were made and seminars with respective scientists were
      held. Field excursions to local markets and interviews with betel quid vendors
      and individual BQ chewers gave further insights. RESULTS: Generally, BQC is on
      the decline in Vietnam. 6.7% of the female population still seems to indulge in
      this habit. In an earlier study, a prevalence of 0.06% of oral cancer was
      reported. In a study of 1084 cases of oral cancer, the male:female ratio was
      1.05:1 (1997). The age group between 60 and 75 years is most often affected by
      oral cancer. In BQ chewing women, the buccal mucosa (27.9%), tongue (23.1%) and
      lips (22.4%) are most often affected. Verrucous carcinoma is seen in the age
      group 70-79 years with women most often being affected (male:female ratio 1:3.4).
      The most important risk factor for oral cancer in women is BQC compared with men
      where smoking, alcohol drinking or combined smoking and drinking habits are the
      most common risk factors. Oral leukoplakia in BQ chewers is observed in 3.8%,
      oral submucous fibrosis in 13%. CONCLUSIONS: BQC in Vietnam is on the decline.
      Association between BQC and oral cancer in elderly women is still of importance.
      Eventually, the BQC habit will vanish and only play a role in socio-ritual
      contexts.

PMID- 18624934
TI  - Serum cytokine and T regulatory cell levels in patients with burning mouth
      syndrome.
AB  - BACKGROUND: Burning mouth syndrome is a disorder usually associated with an
      unexplained, prolonged sensation of burning inside the oral cavity. Although the
      etiology is unknown, neural and psychologic factors and cytokines may be
      implicated in the pathogenesis of burning mouth syndrome. The aim of this study
      was to investigate the relationship between serum cytokine and T regulatory cell
      levels in patients with burning mouth syndrome with regard to depression and
      anxiety. METHODS: Thirty patients with burning mouth syndrome and 30 matched
      controls participated in the study. Serum cytokine levels were measured with
      cytometric bead array and T regulatory cells were defined as CD4(+)CD25(+)Foxp
      3(+) cells by flow cytometry. The level of anxiety and depression were analyzed
      by means of the Speilberger State-Trait Anxiety Inventory and Zung Self-Rating
      Depression Scale. Visual analogue scale was used in the quantification of burning
      levels of patients. RESULTS: Serum IL-2 and TNF-alpha levels were significantly
      decreased in patients with burning mouth syndrome compared with controls [mean
      16.79 +/- 8.70 vs. 37.73 +/- 41.05 pg / ml (P < 0.05) and mean 39.09 +/- 29.40
      vs. 70.83 +/- 42.44 pg / ml (P < 0.01) respectively]. CONCLUSIONS: IL-2 and TNF
      alpha might play a role in burning mouth syndrome. Burning mouth syndrome may
      occur as a sign of predisposition to autoimmunity. Presence of low levels of
      CD28(+) supports the provision that BMS might be a pre-autoimmune disease.

PMID- 18624935
TI  - Immunohistochemical analysis of interleukin-1 alpha, its type I receptor and
      antagonist in keratocystic odontogenic tumors.
AB  - BACKGROUND: Interleukin-1 alpha (IL-1 alpha) is thought to play a crucial role in
      the growth of keratocystic odontogenic tumors (KCOTs) in the jaw. The function of
      IL-1 alpha is regulated by the local levels of IL-1 alpha, its receptor and
      receptor antagonist (IL-1Ra) in tissues. In this study, the expression of these
      proteins was investigated both before and after marsupialization in KCOTs.
      METHODS: The expression of IL-1 alpha, IL-1 receptor type I (IL-1RI) and IL-1Ra
      was detected immunohistochemically in 10 specimens of KCOTs. RESULTS: IL-1 alpha
      was intensively expressed throughout the epithelium in all cases, while mild
      expression of IL-1 alpha was detected in the subepithelial layer endothelial
      cells and fibroblasts. Mild or intensive immunoreactivity for IL-1RI was also
      observed in the epithelial cells in all cases, and in the endothelial cells and
      fibroblasts in five cases respectively. The expression of IL-1Ra was detected in
      the epithelial cells in five cases, and in the endothelial cells and fibroblasts
      in three cases. After marsupialization, the immunoreactivity for IL-1 alpha and
      IL-1RI in the epithelial cells decreased, while the immunoreactivity for IL-1Ra
      in the epithelial cells increased. However, the immunoreactivity for IL-1RI and
      IL-1Ra in endothelial cells and fibroblasts did not change significantly.
      CONCLUSION: The effects of IL-1 alpha on the epithelial cells might be
      downregulated after marsupialization by changing the expression levels of IL-1
      alpha, IL-1RI and IL-1Ra in the epithelium of KCOTs.

PMID- 18624936
TI  - Immune-expression of HSP27 and IL-10 in recurrent aphthous ulceration.
AB  - BACKGROUND: Recently, abnormal cellular immune response has been considered
      responsible for the oral lesion in the recurrent aphthous ulceration (RAU). For
      reasons not yet defined, antigens of the oral microbiota would trigger abnormal
      Th1 immune response against epithelial cells. On the other hand, studies have
      demonstrated that heat shock proteins (HSP) can block the production of
      proinflammatory cytokine through inhibition of NF-kappaB and mitogen-activated
      protein kinase pathways or activate anti-inflammatory cytokines and therefore
      control the magnitude of the immune response. HSP27 has been considered a
      powerful inductor of IL-10, a major inhibitor of Th1 response. METHODS: Using
      immunohistochemistry, we studied the expression and location of HSP27 and IL-10
      in ulcerated lesions clinically diagnosed as RAU (n = 27) and to compare it with
      that of oral clinically normal mucosa (CT; n = 6) and of other inflammatory
      chronic diseases such as oral fibrous inflammatory hyperplasia (FIH; n = 18),
      Crohn's disease (CD; n = 10) and ulcerative colitis (UC; n = 9). RESULTS: A lower
      proportion of HSP27-positive epithelial cells in RAU and CD were observed when
      compared with CT and FIH (P < 0.001**; P = 0.013**). A lower proportion of IL-10
      positive interstitial cells in RAU was observed when compared with FIH, UC, CT
      and CD (P < 0.001**; P < 0.001**; P < 0.001**; P = 0.034*). CONCLUSION:
      Altogether the data suggest that a reduced cellular expression of HSP27 and IL-10
      in RAU might be related with the aetiopathogenesis of the ulcerated oral lesions.

PMID- 18624937
TI  - A novel selective medium for isolation of Aggregatibacter (Actinobacillus)
      actinomycetemcomitans.
AB  - BACKGROUND AND OBJECTIVE: Conventional selective media have been used for the
      selection of Aggregatibacter (Actinobacillus) actinomycetemcomitans in clinical
      samples. The proportion of A. actinomycetemcomitans grown on the selective media
      in vitro may not reflect the true counts in vivo because of the low selectivity.
      A novel selective medium, designated AASM, was developed for the isolation of A.
      actinomycetemcomitans. MATERIAL AND METHODS: AASM was prepared by adding of 200
      microg/mL of vancomycin and 10 U/mL of bacitracin to AAGM, which contains
      dextrose, sodium bicarbonate, trypticase soy, yeast extract and agar. Clinical
      efficacy was evaluated by the recovery, on AASM, of A. actinomycetemcomitans from
      subgingival samples of 44 periodontally healthy subjects and 76 patients with
      chronic periodontitis. RESULTS: All serotypes (a-f) of A. actinomycetemcomitans
      strains grew well, and the average growth recovery of A. actinomycetemcomitans on
      AASM medium was 94.4% (80.0-109.7%) of that on AAGM. The exclusive rate of other
      bacteria was 99.9% in clinical samples cultured on AASM. A. actinomycetemcomitans
      was not detected in periodontally healthy persons but was detected in 25 (32.9%)
      patients with chronic periodontitis. The predominant serotype was c, detected in
      11 subjects. CONCLUSION: The new selective medium, AASM, was highly selective for
      A. actinomycetemcomitans, eliminated possible false-positive results and was
      useful for the isolation of A. actinomycetemcomitans from clinical samples.

PMID- 18624938
TI  - Analysis of the association of polymorphism in the osteoprotegerin gene with
      susceptibility to chronic kidney disease and periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) is a complex disorder,
      which results in several complications involving disturbance of mineral
      metabolism. Periodontal disease is an infectious disease that appears to be an
      important cause of systemic inflammation in CKD patients. Periodontal disease is
      characterized by clinical attachment loss (CAL) caused by alveolar bone
      resorption around teeth, which may lead to tooth loss. Osteoprotegerin (OPG) is a
      key regulator of osteoclastogenesis. Polymorphisms are the main source of genetic
      variation, and single nucleotide polymorphisms (SNPs) have been reported as major
      modulators of disease susceptibility. The aim of this study was to investigate
      the association of a polymorphism located at position -223 in the untranslated
      region of the OPG gene, previously known as -950, with susceptibility to CKD and
      periodontal disease. MATERIAL AND METHODS: A sample of 224 subjects without and
      with CKD (in hemodialysis) was divided into groups with and without periodontal
      disease. The OPG polymorphism was analyzed by polymerase chain reaction and
      restriction fragment length polymorphism. RESULTS: No association was found
      between the studied OPG polymorphism and susceptibility to CKD or periodontal
      disease. CONCLUSION: It was concluded that polymorphism OPG-223 (C/T) was not
      associated with CKD and periodontal disease in a Brazilian population. Studies on
      other polymorphisms in this and other genes of the host response could help to
      clarify the involvement of bone metabolism mediators in the susceptibility to CKD
      and periodontal disease.

PMID- 18624939
TI  - Subculture affects the phenotypic expression of human periodontal ligament cells
      and their response to fibroblast growth factor-2 and bone morphogenetic protein-7
      in vitro.
AB  - BACKGROUND AND OBJECTIVE: Although periodontal ligament cells display several
      osteoblastic traits, their phenotypic expression is still not well established.
      It remains a matter of debate whether they resemble a terminally differentiated
      cell type or an intermediate maturation state that potentially can be directed
      towards a fibroblastic or an osteoblastic phenotype. MATERIAL AND METHODS: To
      explore the characteristics of periodontal ligament cells in greater detail,
      fourth-passage, sixth-passage and eighth-passage human periodontal ligament cells
      were cultured for up to 3 wk. Ki-67, alkaline phosphatase, osteocalcin,
      osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL)
      mRNA expression was quantified by real-time polymerase chain reaction.
      Furthermore, the cellular response to fibroblast growth factor-2 and bone
      morphogenetic protein-7 was examined in first-passage and fourth-passage cells.
      Dermal fibroblasts (1BR.3.G) and osteoblast-like cells (MG63) served as reference
      cell lines. RESULTS: Proliferation decreased over time and was highest in fourth
      passage cells. The expression of differentiation parameters, osteoprotegerin and
      RANKL increased with culture time and was higher in fourth-passage cells than in
      cells of later passages. The RANKL/osteoprotegerin ratio increased steadily until
      day 21. Administration of fibroblast growth factor-2 enhanced cell numbers in
      both passages, whereas alkaline phosphatase and osteocalcin production remained
      unchanged. By contrast, exposure of periodontal ligament cells to bone
      morphogenetic protein-7 resulted in a reduction of cell number in the first and
      fourth passages, whereas the production of alkaline phosphatase and osteocalcin
      was enhanced. In dermal fibroblasts, differentiation parameters did not respond
      to both stimuli. MG63 cells behaved similarly to periodontal ligament cells.
      CONCLUSION: These results indicate that subculture affects the phenotypic
      expression of human periodontal ligament cells with respect to the
      characteristics that these cells share with osteoblasts. Furthermore, the
      periodontal ligament cell phenotype can be altered by fibroblastic and
      osteoblastic growth factors.

PMID- 18624940
TI  - T cells are able to promote lipopolysaccharide-induced bone resorption in mice in
      the absence of B cells.
AB  - BACKGROUND AND OBJECTIVE: T cells and their cytokines are believed to be key
      factors in periodontal disease and bone resorption. We previously showed that T
      cells transferred to nude mice were related to inflammatory bone resorption in
      vivo. However, it has not been clarified whether T cells can induce bone
      resorption in the absence of B cells. In this study, we therefore investigated
      the ability of T cells to induce bone resorption without B cells, using both T
      cell- and B cell-deficient mice with severe combined immune deficiency (SCID).
      MATERIAL AND METHODS: Escherichia coli lipopolysaccharide (LPS) was injected into
      the gingivae of SCID mice reconstituted by T cells (SCID + T mice). Wild-type C.B
      17 mice and SCID mice were used as control animals. Alveolar bone resorption and
      production of cytokines in the gingivae were then compared histopathologically
      and immunohistologically. RESULTS: The degree of bone resorption in SCID + T mice
      was significantly greater than that in SCID mice but less than that in wild-type
      mice. The same tendency was found for expression of receptor activator of nuclear
      factor kappaB ligand. The number of interferon-gamma-positive cells in SCID + T
      mice was the highest of the three groups. In contrast, interleukin-4-positive
      cells were detected in wild-type mice but not in SCID + T and SCID mice.
      CONCLUSION: The results suggest that T cells are able to promote LPS-induced bone
      resorption in the absence of B cells. The expressions of cytokines in the
      presence of B cells are quite different.

PMID- 18624941
TI  - Putative stem cells in regenerating human periodontium.
AB  - BACKGROUND AND OBJECTIVE: Human postnatal stem cells have been identified in
      periodontal ligament, with the potential to regenerate the periodontium in vivo.
      However, it is unclear if periodontal ligament stem cells are present in
      regenerating periodontal tissues. The aim of this study was to identify and
      localize putative stem cells in block biopsies and explant cultures of
      regenerating human periodontal tissues. MATERIAL AND METHODS: Guided tissue
      regeneration was carried out on the molars of three human volunteers. After 6 wk,
      the teeth with the surrounding regenerating tissues and bone were surgically
      removed and processed for immunohistochemistry. The mesenchymal stem cell
      associated markers STRO-1, CD146 and CD44 were used to identify putative stem
      cells. Cell cultures established from regenerating tissue explants were analysed
      by flow cytometry to assess the expression of these markers. Mineralization,
      calcium concentration and adipogenic potential of regenerating tissue cells were
      assessed and compared with periodontal ligament stem cells, bone marrow stromal
      stem cells and gingival fibroblasts. RESULTS: STRO-1(+), CD44(+) and CD146(+)
      cells were identified in the regenerating tissues. They were found mainly in the
      paravascular and extravascular regions. Flow cytometry revealed that cultured
      regenerating tissue cells expressed all three mesenchymal stem cell associated
      markers. The regenerating tissue cells were able to form mineral deposits and
      lipid-containing adipocytes. However, the level of mineralization in these cells
      was lower than that of periodontal ligament stem cells and bone marrow stromal
      stem cells. CONCLUSION: Cells with characteristics of putative mesenchymal stem
      cells were found in regenerating periodontal tissues, implying their involvement
      in periodontal regeneration.

PMID- 18624942
TI  - Areca nut extract represses migration and differentiation while activating matrix
      metalloproteinase-9 of normal gingival epithelial cells.
AB  - BACKGROUND AND OBJECTIVE: Areca (betel) chewing is associated with an increase in
      the incidence of periodontal diseases. Aberrations in matrix metalloproteinase
      (MMP) expression have been reported to be associated with periodontal disease.
      This study investigated the effects of areca nut extract on MMP activity and the
      phenotype of human gingival epithelial cells. MATERIAL AND METHODS: Reverse
      transcription-polymerase chain reaction, western blotting and gelatin zymography
      were used to assay MMPs. Cell viability, mobility and detachment assays were
      performed to characterize the phenotypic impact. Confocal microscopy was employed
      to evaluate cell aggregation and the distribution of E-cadherin and F-actin.
      RESULTS: Treatment of gingival epithelial cells with 10 microg/mL of areca nut
      extract reduced its cell viability. Treatment with 5 and 10 microg/mL of areca
      nut extract for 24 h activated MMP-9 but not MMP-2 in gingival epithelial cells.
      This activation could be nuclear factor-kappaB dependent and was abrogated by 10
      microM curcumin. Areca nut extract also reduced the migration and detachment of
      gingival epithelial cells. The differentiated cell-cell contact of gingival
      epithelial cells was markedly impaired by areca nut extract. This was accompanied
      by a disruption of distribution of E-cadherin and F-actin. CONCLUSION: The areca
      nut extract-mediated activation of MMP-9 in gingival epithelial cells could
      signify a potential periodontal pathogenesis in areca chewers. The areca nut
      extract-mediated inhibition of cell viability and migration, together with the
      changed aggregation in gingival epithelial cells, suggests that impairment of the
      re-epithelization underlies the process and this, in turn, might exacerbate
      gingival inflammation.

PMID- 18624943
TI  - Apical tooth germ cell-conditioned medium enhances the differentiation of
      periodontal ligament stem cells into cementum/periodontal ligament-like tissues.
AB  - BACKGROUND AND OBJECTIVE: Limitations of current periodontal regeneration
      modalities in both predictability and extent of healing response, especially on
      new cementum and attachment formation, underscore the importance of restoring or
      providing a microenvironment that is capable of promoting the differentiation of
      periodontal ligament stem cells (PDLSCs) towards cementoblast-like cells and the
      formation of cementum/periodontal ligament-like tissues. The aim of this study
      was to investigate the biological effect of conditioned medium from developing
      apical tooth germ cells (APTG-CM) on the differentiation and cementogenesis of
      PDLSCs both in vitro and in vivo. MATERIAL AND METHODS: Using the limiting
      dilution technique, single-colony-derived human PDLSCs were isolated and expanded
      to obtain homogeneous populations of PDLSCs. Morphological appearance, cell cycle
      analysis, bromodeoxyuridine incorporation, alkaline phosphatase (ALP) activity,
      mineralization behavior, gene expression of cementoblast phenotype and in vivo
      differentiation capacities of PDLSCs co-cultured with APTG-CM were evaluated.
      RESULTS: The induced PDLSCs exhibited several characteristics of cementoblast
      lineages, as indicated by the morphological changes, increased proliferation,
      high ALP activity, and the expression of cementum-related genes and calcified
      nodule formation in vitro. When transplanted into immunocompromised mice, the
      induced PDLSCs showed tissue-regenerative capacity to produce
      cementum/periodontal ligament-like structures, characterized by a layer of
      cementum-like mineralized tissues and associated periodontal ligament-like
      collagen fibers connecting with the newly formed cementum-like deposits, whereas
      control, untreated PDLSCs transplants mainly formed connective tissues.
      CONCLUSION: Our findings suggest that APTG-CM is able to provide a cementogenic
      microenvironment and induce differentiation of PDLSCs along the cementoblastic
      lineage. This has important implications for periodontal engineering.

PMID- 18624944
TI  - Interleukin-4, a T-helper 2 cell cytokine, is associated with the remission of
      periodontal disease.
AB  - BACKGROUND AND OBJECTIVES: Interleukin-4 (IL-4), secreted mainly by T-helper 2
      cells, is a key cytokine for the growth and proliferation of B lymphocytes.
      Previous studies have proved that IL-4 has an anti-inflammatory effect owing to
      its efficient inhibition of the production of proinflammatory cytokines such as
      tumour necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-1beta, IL-6 and IL-8 by
      monocytes/macrophages. The aim of the present study was to assess the relation
      between clinical parameters and concentrations of IL-4 within gingival crevicular
      fluid from inflamed gingiva and periodontitis sites and, subsequently, after
      treatment of the periodontitis sites. MATERIAL AND METHODS: A total of 60
      subjects were divided into three groups based on gingival index (GI), pocket
      probing depth and clinical attachment loss (CAL): healthy (group 1), gingivitis
      (group 2) and chronic periodontitis (group 3). A fourth group (group 4) consisted
      of 20 subjects from group 3, 6-8 weeks after treatment (i.e. scaling and root
      planing). Gingival crevicular fluid samples collected from each patient were
      quantified for IL-4 using the enzymatic immunometric assay. RESULTS: The highest
      mean concentration of IL-4 was obtained for group 1 (99.39 +/- 49.33 pg/mL) and
      the lowest mean concentration of IL-4 was obtained for group 3 (15.78 +/- 21.92
      pg/mL). The mean IL-4 concentrations for group 2 (64.34 +/- 39.56 pg/mL) and
      group 4 (68.92 +/- 42.85 pg/mL) were intermediate between the levels in healthy
      subjects and periodontitis subjects. CONCLUSION: The mean concentration of IL-4
      decreased from periodontal health to disease. Thus, we suggest that type 2 helper
      T cell cytokine, as represented by IL-4, was associated with the remission or
      improvement of periodontal disease.

PMID- 18624945
TI  - Analysis of the capsular polysaccharide biosynthesis locus of Porphyromonas
      gingivalis and development of a K1-specific polymerase chain reaction-based
      serotyping assay.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is a gram-negative obligate
      anaerobe that is strongly associated with severe periodontitis. Previous reports
      showed an association of P. gingivalis capsular polysaccharide with virulence.
      The K1 capsular polysaccharide was found to be more immunostimulatory than the
      other serotypes. Our objective was to explore the genetic background of the
      capsule biosynthesis (K-antigen) locus in a representative group of K1 serotype
      strains. MATERIAL AND METHODS: We used restriction fragment length polymorphism,
      polymerase chain reaction (PCR) and DNA sequencing to study the capsular
      polysaccharide locus in P. gingivalis K1 strains. For serotyping by double
      immunodiffusion and PCR we used 32 strains of P. gingivalis, including strains of
      all six known K serotypes. RESULTS: All tested K1 strains showed high
      conservation of the capsular polysaccharide locus, although a DNA re-arrangement
      was found in two strains. Based on this information a K1-specific PCR-based
      serotyping assay was designed. The specificity and sensitivity of this test were
      confirmed using non-K1 P. gingivalis serotypes. CONCLUSION: The capsular
      polysaccharide locus of P. gingivalis is conserved but may vary slightly among K1
      strains. The new K1 serotyping assay presented here is much faster than double
      immunodiffusion and can detect K1 strains in a very selective and sensitive way.
      This method may therefore be clinically relevant in the detection of the virulent
      P. gingivalis K1 serotype.

PMID- 18624947
TI  - Periodontal tissue engineering by transplantation of multilayered sheets of
      phenotypically modified gingival fibroblasts.
AB  - BACKGROUND AND OBJECTIVE: In periodontal tissue engineering, the sourcing of most
      of the relevant cells is limited by poor accessibility, whereas the use of
      readily available gingival fibroblasts is hampered because of their inhibitory
      effects on bone formation. To address the latter drawback, we developed a new
      graft composed of fibronectin (FN) matrix-based multilayered cell sheets of human
      gingival fibroblasts modified to express alkaline phosphatase (ALP). This study
      was undertaken to investigate the effects of this graft, called the FN-ALP
      transplant, on the healing of periodontal defects in a rat model. MATERIAL AND
      METHODS: The FN-ALP transplants were grafted into periodontal fenestration bone
      defects in immunosuppressed rats. The process of periodontal healing was examined
      by histology, histomorphometry and immunohistochemistry. Grafted cells were
      tracked by immunostaining with human-specific antibodies. Control groups included
      non-transplanted empty defects and defects to which cell sheets without ALP
      induction had been grafted. RESULTS: After implantation, the FN-ALP transplants
      healed alveolar bone defects by intramembranous ossification, with formation of
      cementum and periodontal ligament. Moreover, FN-ALP transplants increased new
      bone formation, by endochondral ossification, on the mandibular cortex adjacent
      to the defect. Grafted fibroblasts were located near host osteoblasts and
      chondrocyte precursor cells early in the ossification process but were
      undetectable on and in newly formed bone and cartilage. CONCLUSION: These results
      indicate that the FN-ALP transplants support alveolar bone regeneration within
      the defect and augment bone formation outside the defect through the recruitment
      of host osteo/chondrogenic cells, suggesting their potential for periodontal
      tissue engineering applications.

PMID- 18624948
TI  - Insulin-like growth factor binding protein-5 enhances the migration and
      differentiation of gingival epithelial cells.
AB  - BACKGROUND AND OBJECTIVE: The objective was to define the roles of insulin-like
      growth factor binding protein-5 (IGFBP-5) in gingival epithelial cells (GEC).
      Human IGFBP-5 is expressed in many cell types and has diverse biological
      functions. It stimulates the growth of bone cells and is associated with the
      impedance of gingival fibroblast apoptosis. In gingival epithelium, IGFBP-5 is
      expressed in the cells of the differentiated stratum spinosum layer. MATERIAL AND
      METHODS: Recombinant IGFBP-5 protein treatment and knockdown of IGFBP-5
      expression using a lentivirus-delivered short hairpin RNA was carried out in
      human GEC. Proliferation, apoptosis, anoikis, migration, differentiation and gene
      expression in GEC were analyzed and molecular images were obtained. RESULTS: The
      IGFBP-5 had no effect on proliferation, but it slightly suppressed apoptosis and
      anoikis of GEC. It also induced GEC migration and upregulated the expression of
      involucrin, transglutaminase-1, keratin and focal adhesion kinase. The IGFBP-5
      induced migration partly via an insulin-like growth factor-independent mechanism.
      The knockdown of IGFBP-5 downregulated the expression of involucrin,
      transglutaminase-1 and focal adhesion kinase. CONCLUSION: Expression of IGFBP-5
      in GEC is associated with anti-apoptosis, migration and differentiation of GEC.
      These phenotypic effects may be associated with focal adhesion kinase and are
      advantageous for re-epithelization of GEC and the maintenance of gingival health.

PMID- 18624949
TI  - Fractal analysis of dental radiographs to detect periodontitis-induced trabecular
      changes.
AB  - BACKGROUND AND OBJECTIVE: The aim was to evaluate fractal analysis as a tool to
      quantitatively measure the impact of periodontal disease on surrounding bone. The
      diagnosis of periodontitis is based on information obtained from clinical and
      radiographic examinations. The current standard use of dental radiographs is
      visual inspection, often with no quantitative analysis. Fractal analysis can be
      used to examine trabecular bone patterns among periodontal patients. MATERIAL AND
      METHODS: Patients (n = 108) from the University of Southern California School of
      Dentistry were classified into three groups: healthy, moderate and severe
      periodontitis. A region of interest was selected from periapical radiographs.
      Image processing was applied to correct for lighting irregularity, and the box
      counting method was used to calculate a fractal dimension. ANOVA and ANCOVA were
      used to measure fractal dimension differences between all groups. RESULTS:
      According to the statistical tests, significant differences in average fractal
      dimensions were measured between healthy and moderate periodontitis groups (p <
      0.01) and between healthy and severe periodontitis groups (p < 0.001). Higher
      fractal dimensions were measured in healthy periodontal patients. CONCLUSION:
      Fractal analysis evidenced significant differences between patients affected and
      not affected by periodontitis. The box-counting method quantitatively describes
      the severity of bone disease and can be used to improve current diagnostic
      techniques.

PMID- 18624950
TI  - Tetracycline release from tripolyphosphate-chitosan cross-linked sponge: a
      preliminary in vitro study.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to design a tripolyphosphate
      chitosan cross-linked tetracycline-containing (TPP-TC) sponge that slowly
      releases tetracycline, for future periodontal applications. MATERIAL AND METHODS:
      Chitosan sponge was made by freezing and drying 2.5% chitosan solution.
      Tripolyphosphate-chitosan cross-linked (TPP) sponge was made by immersing the
      chitosan sponge in tripolyphosphate solution and air drying it. Tetracycline
      containing chitosan (TC) sponge was prepared by freezing and drying a mixture of
      chitosan and tetracycline. TPP-TC sponge was made by immersing the TC sponge in
      tripolyphosphate solution. The weight, thickness and diameter of the four
      chitosan sponges were recorded. Their surface microstructures were inspected
      using scanning electron microscopy. The amount of tetracycline released from the
      sponges was analyzed by spectrophotometry. Antimicrobial activities of the
      residual sponges were tested against Staphylococcus aureus and Escherichia coli.
      RESULTS: The topography of the scaffolds was intact after the addition of
      tetracycline. However, increased surface irregularities were noted. In sponges
      with tripolyphosphate, intensified surface folding was observed. The weight of
      the sponges increased after tripolyphosphate and tetracycline were added, but
      their thicknesses and diameters decreased after cross-linking. Tetracycline was
      detected in the solution containing TPP-TC sponges until day 11. On day 7, the
      tetracycline released from TC sponges was less than that released from TPP-TC
      sponges. Bacterial growth was inhibited by sponges containing tetracycline. The
      inhibitory effect of the TPP-TC sponges was detectable until day 11. CONCLUSION:
      Our data showed that TPP-TC sponge was suitable as a slow-release device for
      tetracycline and that it maintained antimicrobial effects against the bacteria
      tested for up to 11 d.

PMID- 18624951
TI  - CXCL13 expression and follicular dendritic cells in relation to B-cell
      infiltration in periodontal disease tissues.
AB  - BACKGROUND AND OBJECTIVE: B lymphocyte is the dominant infiltrating cell type in
      periodontitis lesions. CXCL13, produced by follicular dendritic cells,
      endothelial cells and fibroblasts, is crucial for B-cell trafficking. An
      association between chronic inflammation and lymphoid organogenesis has been
      reported in infection and in autoimmune responses, in which T-cell/B-cell
      follicles with a follicular dendritic cell network are formed. The aim of this
      study was to examine CXCL13 expression and follicular dendritic cell distribution
      in relation to B-cell infiltration in chronic inflammatory periodontal lesions.
      MATERIAL AND METHODS: Fifty-eight gingival tissue biopsies from patients with
      periodontitis and 25 samples from subjects with gingivitis were analyzed. Gene
      expression for CXCL13 and for the CD21 long isoform was analyzed using the
      reverse transcription-polymerase chain reaction. Immunohistochemical analysis was
      performed using antibodies to CXCL13, CXCR5, follicular dendritic cells, CD3 and
      CD19 on serial cryostat sections. RESULTS: mRNA for CXCL13 was expressed in both
      periodontitis and gingivitis tissues. The number of CXCL13+ cells was
      significantly higher in periodontitis than in gingivitis in connective tissues
      subjacent to the pocket epithelium and positively correlated with the number of
      CD19+ cells. CXCL13+ cells were distributed in B-cell-dominant areas both with
      and without follicular dendritic cells. Although obvious reticular networks of
      follicular dendritic cells were not found in periodontitis and gingivitis, the
      accumulation of follicular dendritic cells in B-cell-dominant areas in
      periodontitis was observed in some patients. CONCLUSION: These findings suggested
      that CXCL13 and follicular dendritic cells were involved in B-cell recruitment
      to, and B-cell distribution in, chronic inflammatory periodontal lesions.

PMID- 18624952
TI  - Injectable growth/differentiation factor-5-recombinant human collagen composite
      induces endochondral ossification via Sry-related HMG box 9 (Sox9)expression and
      angiogenesis in murine calvariae.
AB  - BACKGROUND AND OBJECTIVE: The types of collagens available today as biomaterials
      are purified from animal tissues. A major growing concern, however, is their
      safety, since there are risks of viral and prion contamination and of unknown and
      potentially zoonotic infectious diseases. The present study aimed to assess,
      using immunohistochemistry, the effects of recombinant human
      growth/differentiation factor-5 (rhGDF-5) combined with recombinant human
      collagen I (rhCI) on bone formation in murine calvariae. MATERIAL AND METHODS:
      Composite rhGDF-5-rhCI or rhCI alone was injected subcutaneously into murine
      calvariae. After 3, 7 or 14 days, tissues were examined radiologically,
      histologically and immunohistochemically. The production of vascular endothelial
      growth factor (VEGF) by primary osteoblasts, periosteal cells and connective
      tissue fibroblasts isolated enzymatically from neonatal murine calvariae was also
      assessed. RESULTS: A protrusion was observed on the calvariae at the site
      injected with rhGDF-5/rhCI composite. Its mineral density was shown to be
      different from that of the existing bone by two-dimensional microcomputed
      tomography. Type II collagen-positive staining was restricted to newly formed
      tissues. Thus, the newly formed tissues seemed to be bone- and cartilage-like
      tissues. A number of vessels with positively stained cells for Von Willebrand
      factor were detected in the newly formed tissues. The rhGDF-5 enhanced VEGF
      production in cultured connective tissue fibroblasts. Sry-related HMG box 9
      (Sox9)-positive cells were detected in the hypertrophic periosteum, and
      penetrated into the newly formed tissues. CONCLUSIONS: These results suggest that
      rhCI seems to allow the release of rhGDF-5 and that rhGDF-5-rhCI composite
      induces endochondral ossification via Sox9 expression and angiogenesis in murine
      calvariae.

PMID- 18624953
TI  - Expression of metalloproteinases and their tissue inhibitors in inflamed gingival
      biopsies.
AB  - OBJECTIVES: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs)
      are known to be involved in the periodontal disease process. Results of in vivo
      MMPs and TIMPs gene expressions in the gingiva, though, are still controversial.
      In the present study, we compared the gene expression of MMP-1, -2, -9, -13 and
      TIMP-1, -2 in healthy and inflamed gingiva. METHODS: 38 gingival samples were
      collected from gingivitis (n = 10), advanced chronic periodontitis (n = 10),
      generalized aggressive periodontitis (n = 8) and periodontally healthy
      individuals (n = 10). Total RNA isolated from those samples was subjected to
      reverse transcription followed by amplification by polymerase chain reaction (RT
      PCR). Products were visualized in agarose gels and quantified by optical
      densitometry. Samples were also processed for gelatin zymography and Western
      blotting for MMP-2 and MMP-9 in order to assess for post-transcriptional MMP
      regulation at the protein level. RESULTS: The frequencies and levels of
      transcripts encoding MMPs and TIMPs were found to be not significantly different
      among groups (p > 0.05, Fisher's Exact and Kruskall-Wallis tests). There is a
      trend towards higher MMP-2 and -9 gelatinase activities in the inflamed samples,
      although not statistically significant. In contrast, zymography and Western
      blotting studies show that MMP-2 is virtually absent in the chronic periodontitis
      group. CONCLUSION: These results could reflect a complex regulation of MMPs and
      TIMPs' gene expression in the course of gingival inflammation. They also reveal a
      great biological diversity even among individuals with similar periodontal
      status.

PMID- 18624954
TI  - Human periodontal ligament: a niche of neural crest stem cells.
AB  - BACKGROUND AND OBJECTIVE: The periodontal ligament is a specialized connective
      tissue, derived from dental follicle and originated from neural crest cells.
      Recently it has been suggested, based on animal models, that periodontal ligament
      could be a niche for neural crest stem cells. However, there is still little
      knowledge on this subject. The identification of neural crest adult stem cells
      has received much attention based on its potential in tissue regeneration. The
      objective of the present work was to verify the human periodontal ligament as a
      niche for neural crest stem cells. MATERIAL AND METHODS: Cells from human
      periodontal ligament were isolated from 10 teeth of seven individuals
      (periodontal ligament pool group) and also from four teeth of one individual
      (periodontal ligament single group), after enzymatic digestion. The cells were
      cultured in specific inductive medium. Analyses of protein and gene expression
      were performed through immunocytochemistry and reverse transcription-polymerase
      chain reaction techniques, respectively. RESULTS: Mesodermal phenotypes
      (adipogeneic, osteogenic and myofibroblastic) were identified after culture in
      inductive medium. Immunocytochemistry analyses showed the presence of the nestin
      marker of neural stem cells and also markers of undifferentiated neural crest
      cells (HNK1, p75). When cultured in inductive medium that allowed neural
      differentiation, the cells showed markers for beta-tubulin III, neurofilament M,
      peripherin, microtubule-associated protein 2 and protein zero. The results were
      similar between the two study groups (the periodontal ligament pool group and the
      periodontal ligament single group). CONCLUSION: This research provides evidence
      that human periodontal ligament, in addition to its mesodermal derivatives,
      produces neural crest-like cells. Such features suggest a recapitulation of their
      embryonic state. The human periodontal ligament revealed itself as a viable
      alternative source for possible primitive precursors to be used in stem-cell
      therapies.

PMID- 18624955
TI  - Melatonin decreases matrix metalloproteinase-9 activation and expression and
      attenuates reperfusion-induced hemorrhage following transient focal cerebral
      ischemia in rats.
AB  - We have previously shown that melatonin reduces postischemic rises in the blood
      brain barrier (BBB) permeability and improves neurovascular dysfunction and
      hemorrhagic transformation following ischemic stroke. It is known that activation
      of the matrix metalloproteinases (MMPs) plays a crucial role in the pathogenesis
      of brain edema and hemorrhagic transformation after ischemic stroke. We, herein,
      investigated whether melatonin would ameliorate MMP-2 and MMP-9 activation and
      expression in a rat model of transient focal cerebral ischemia. Adult male
      Sprague-Dawley rats were subjected to a 90-min middle cerebral artery (MCA)
      occlusion using an intraluminal filament. Melatonin (5 mg/kg) or vehicle was
      intravenously injected upon reperfusion. Brain infarction and hemorrhage within
      infarcts were measured, and neurological deficits were scored. The activity and
      expression of MMP-2 and MMP-9 were determined by zymography, in situ zymography
      and Western immunoblot analysis. Cerebral ischemia-reperfusion induced increased
      pro-MMP-9 and MMP-9 activity and expression 24 hr after reperfusion onset.
      Relative to controls, melatonin-treated animals, however, had significantly
      reduced levels in the MMP-9 activity and expression (P < 0.01), in addition to
      reduced brain infarct volume and hemorrhagic transformation as well as improved
      sensorimotor neurobehavioral outcomes. No significant change in MMP-2 activity
      was observed throughout the course experiments. Our results indicate that the
      melatonin-mediated reductions in ischemic brain damage and reperfusion-induced
      hemorrhage are partly attributed to its ability to reduce postischemic MMP-9
      activation and increased expression, and further support the fact that melatonin
      is a suitable as an add-on to thrombolytic therapy for ischemic stroke patients.

PMID- 18624956
TI  - Melatonin in grape, not just a myth, maybe a panacea.

PMID- 18624957
TI  - Increased melatonin synthesis in pineal glands of rats in streptozotocin induced
      type 1 diabetes.
AB  - It is well-documented that melatonin influences insulin secretion. The effects
      are mediated by specific, high-affinity, pertussis-toxin-sensitive, G protein
      coupled membrane receptors (MT(1) as well MT(2)), which are present in both the
      pancreatic tissue and islets of rats and humans, as well as in rat insulinoma
      cells (INS1). Via the Gi-protein-adenylatecyclase-3',5'-cyclic adenosine
      monophosphate (cAMP) and, possibly, the guanylatecyclase-cGMP pathways, melatonin
      decreases insulin secretion, whereas, by activating the Gq-protein-phospholipase
      C-IP(3) pathway, it has the opposite effect. For further analysis of the
      interactions between melatonin and insulin, diabetic rats were investigated with
      respect to melatonin synthesis in the pineal gland and plasma insulin levels. In
      this context, recent investigations have proven that type 2 diabetic rats and
      humans display decreased melatonin levels, whereas type 1 diabetic IDDM rats or
      those with diabetes induced by streptozotocin (STZ) of the present study show
      increased plasma melatonin levels and elevated AA-NAT-mRNA. Furthermore, the mRNA
      of pineal insulin receptors and beta1-adrenoceptors, including the clock genes
      Per1 and Bmal1 and the clock-controlled output gene Dbp, increases in both young
      and middle-aged STZ rats. The results therefore indicate that the decreased
      insulin levels in STZ-induced type 1 diabetes are associated with higher
      melatonin plasma levels. In good agreement with earlier investigations, it was
      shown that the elevated insulin levels observed in type 2 diabetes, are
      associated with decreased melatonin levels. The results thus prove that a
      melatonin-insulin antagonism exists. Astonishingly, notwithstanding the drastic
      metabolic disturbances in STZ-diabetic rats, the diurnal rhythms of the
      parameters investigated are maintained.

PMID- 18624958
TI  - Effects of natriuretic peptides on intracavernous pressure and blood pressure in
      conscious rats.
AB  - INTRODUCTION: Natriuretic peptides activate particulate guanylyl cyclases and
      have been shown to induce penile erection in rats, rabbits, and humans. AIM: We
      investigated the effects of atrial natriuretic peptide (ANP), brain natriuretic
      peptide (BNP), and C-type natriuretic peptide (CNP) on intracavernous pressure
      (ICP) and systemic blood pressure (BP) in conscious, free-moving rats. METHODS:
      ICP and BP were measured in male Sprague-Dawley rats after catheters were
      inserted into the crus corpus cavernosum and carotid artery, respectively.
      Natriuretic peptides were given by intravenous bolus (3, 10, and 30 nmol/kg) or
      continuous (0.1 and 1 nmol/kg/minute) administration. MAIN OUTCOME MEASURES: The
      number of animals with increases in ICP were determined. Amplitudes and durations
      of ICP responses and changes in BP were also evaluated. RESULTS: More animals had
      multiple transient increases of ICP in response to ANP and BNP than to CNP. The
      increases in ICP were transient and appeared to be an "all or none" response. ANP
      and BNP decreased BP more than CNP, especially with bolus administration.
      CONCLUSIONS: These findings show that in rats, erectile responses can be
      initiated by ANP, BNP, and less effectively, by CNP. ANP and BNP have a high
      affinity for the natriuretic peptide receptor-A, suggesting that this receptor is
      involved in the responses.

PMID- 18624959
TI  - The associations between serum sex hormones, erectile function, and sex drive:
      the Olmsted County Study of Urinary Symptoms and Health Status among Men.
AB  - INTRODUCTION: Testosterone replacement therapy has been used in the treatment of
      sexual dysfunction; however, its use remains controversial, and the effectiveness
      and long-term health implications are unknown. AIM: To evaluate the association
      between sex hormone serum levels, erectile function, and sexual drive in a
      population-based sample of men. METHODS: A stratified random sample of men
      residing in Olmsted County, Minnesota, completed a questionnaire containing
      questions from the Brief Male Sexual Function Inventory (BMSFI), and participated
      in a clinical exam, which included serum hormone measurements. MAIN OUTCOME
      MEASURES: Levels of sexual drive (libido) and erectile function as assessed by
      the BMSFI and serum testosterone, bioavailable testosterone, and estradiol
      measurements. RESULTS: Out of 414 men, 294 had a regular sexual partner and
      androgen measurements at the 14th year of follow-up. Total testosterone and
      erectile function were significantly correlated even after adjustment for age (r
      = 0.12, P = 0.04). Conversely, total testosterone was not significantly
      correlated with sex drive (r = 0.08, P = 0.17). Bioavailable testosterone was
      significantly correlated with both erectile function and sex drive (r = 0.16, P =
      0.01 and r = 0.20, P = 0.001, respectively). However, these associations
      disappeared after age adjustment (r = 0.04 and r = 0.09). CONCLUSIONS: These
      cross-sectional results suggest the relationship between sex hormones and sexual
      function is complex, and that the age-related decline in sexual function may be
      due to age-related declines in levels of bioavailable testosterone rather than
      total testosterone levels.

PMID- 18624960
TI  - Correlation of the erectile dysfunction with lesions of cerebrovascular
      accidents.
AB  - INTRODUCTION: The recent human and animal studies indicate that the central
      supraspinal systems controlling penile erection, which are localized
      predominantly in the parts of the frontal lobe and limbic system, are reported to
      be involved in erection. AIM: The purpose of this study was to elucidate the
      correlation of the erectile dysfunction (ED) with lesions of cerebrovascular
      accidents (CVA). METHODS: Forty-four men were selected among the CVA patients who
      had visited our hospital between March and July 2006. The audiovisual sexual
      stimulation (AVSS) test was conducted using Rigiscan device on the patients,
      whose erectile domain score of the International Index of Erectile Function
      Questionnaire (IIEF) was less than 22. The criteria for adequate erectile
      function was the erectile events of > 60% rigidity for > or = 5 minutes. The CVA
      lesions were classified into frontal lobe, cortex except frontal lobe, basal
      ganglia, thalamus, and other area. Each CVA lesions of ED group and non-ED group
      were compared. MAIN OUTCOME MEASURE: IIEF, AVSS using Rigiscan. RESULT: Thirty
      eight patients' erectile domain score of IIEF were less than 22, and the AVSS
      test was conducted on them. Eighteen patients showed no ED, and 20 patients
      showed ED. The mean age of the ED group was 60.40 +/- 2.2, and the mean age of
      non-ED group was 55.29 +/- 1.85. There was no statistically significant
      difference between the mean age of both groups (P = 0.081). As each CVA lesions
      of both groups were compared, the CVA lesions of the thalamic area in the ED
      group were significantly more than in the non-ED group (P = 0.010). CONCLUSIONS:
      Patients (47.4%) who were suggestive of ED in the IIEF has no ED in the AVSS
      test. The patients who had CVA lesions in the thalamic area more commonly showed
      ED than the patients with CVA lesions of any other areas.

PMID- 18624961
TI  - Cortisol, sexual arousal, and affect in response to sexual stimuli.
AB  - INTRODUCTION: Theoretically, the physiological response to stress should inhibit
      the sexual response. This has been demonstrated experimentally in animal models,
      and correlationally in studies of human reproduction. It is reasonable to expect,
      then, that the stress response would be blunted during sexual arousal, and
      several researchers have found a pattern of decreasing cortisol during sexual
      arousal. AIM: In the present study, we explored individual differences in women's
      cortisol response to sexual arousal in a laboratory setting. We also examined how
      cortisol response in the laboratory related to a validated measure of sexual
      arousal functioning in real life. MAIN OUTCOME MEASURES: Cortisol levels were
      measured in saliva via enzyme immunoassay. Subjective arousal was measured by a
      self-report questionnaire, and genital arousal was measured by a vaginal
      photoplethysmograph. METHODS: Subjective and physiological responses to an erotic
      film were assessed in 30 women. Saliva samples were taken at baseline and
      following the film. RESULTS: The majority of women (N = 20) showed a decrease in
      cortisol; nine women showed an increase in response to an erotic film. The women
      who showed an increase in cortisol had lower scores on the Arousal, Desire, and
      Satisfaction domains of the Female Sexual Function Index. Genital arousal in the
      laboratory was not related to cortisol change. CONCLUSIONS: Women who show an
      increase in cortisol in response to sexual stimuli in the laboratory have lower
      levels of functioning in certain areas of their sexual life compared with women
      who show a decrease in cortisol. Stress related to sexual performance may
      interfere with sexual arousal.

PMID- 18624962
TI  - The menopausal transition--endocrinology.
AB  - INTRODUCTION: The Melbourne Women's MidLife Health Project (MWMHP) and related
      studies have yielded valuable information regarding the endocrine changes of the
      menopausal transition, which are summarized in this review. AIM: To describe the
      endocrinology of the menopause transition. MAIN OUTCOME MEASURES: Includes
      changes in inhibins A and B, follicle stimulating hormone (FSH), and estradiol,
      cross-sectionally in regularly cycling volunteers, and longitudinally (including
      testosterone) in women passing through the menopause transition. METHODS: Early
      follicular phase hormone concentrations were measured by well-characterized
      immunoassays in normal volunteers aged 20-50 years, and in 438 subjects initially
      recruited between ages 45 and 55 for a longitudinal study of the menopause
      transition, the MWMHP, in which annual blood samples were obtained. The data
      summarized here includes the first 6 years of follow-up. These volunteers also
      recorded menstrual cycle data and responded to detailed annual questionnaires.
      RESULTS: In regularly cycling female volunteers aged more than 40 years, it was
      established that inhibin B is a significant determinant of circulating FSH
      levels. From the MWMHP, the central endocrine event marking the onset of
      menstrual irregularity was shown to be a fall in follicular phase inhibin B
      concentrations, with a nonsignificant rise in FSH and no change in estradiol or
      inhibin A. Cross-sectional analysis of data from women in the early stages of the
      MWMHP showed a wide variation in circulating FSH levels, irrespective of
      menopausal status, indicating that single FSH measurements provide little useful
      information regarding menopausal status. Based on the prospective determination
      of the date of final menses (FMP), it was shown that estradiol levels begin to
      fall and FSH levels to rise about 2 years before FMP. At the time of FMP, FSH
      levels were approximately 50% of those ultimately reached postmenopausally, while
      estradiol had fallen by approximately 50% from reproductive age levels. Despite a
      major decline in sexual function, as women transited the menopause, there was no
      significant decline in circulating testosterone levels, the decline in sexual
      function being correlated with the decline in estradiol, not testosterone.
      Analysis of data from related studies showed that endocrinologically normal
      ovulatory cycles could be observed in women who had already experienced cycle
      irregularity, even more than 3 months of amenorrhea, and could occur close to or
      at the time of FMP. CONCLUSIONS: An extensive database on the endocrinology of
      the menopause transition, including both cross-sectional and longitudinal
      information, has been obtained.

PMID- 18624963
TI  - Obesity and sexual dysfunction in younger Danish men.
AB  - INTRODUCTION: Proportion of populations that are overweight and obese are on the
      rise and generally affecting more than 50% of the adult Western male population.
      It is, therefore, of interest to look at possible associations between obesity
      and sexual function in a homogeneous population. AIM: To examine a possible
      association between sexual disorders (erectile dysfunction, ejaculatory
      disorders, and sexual desire disorders) and obesity among younger men born and
      living in Denmark. METHODS: A community-based cross-sectional study of sexual
      health among Danish younger men. Questionnaires were mailed to 3,300 men, aged 20
      45 years and divided into six 5-year age cohorts. Odds ratios were calculated
      using logistic regression modeling. In total, 863 men (26%) responded
      anonymously. A similar set of data from 600 older men aged 50-75 years and from
      same community was used for comparison. MAIN OUTCOME MEASURES: The associations
      between self-reported erectile, ejaculatory and desire disorders, and body mass
      index (BMI) were examined, stratified by age group and smoking status. RESULTS:
      The material was found to be generally representative of the Danish population of
      men of similar age in regard to height, weight, smoking status, and alcohol
      consumption. Erectile dysfunction (ED) was more prevalent among these younger and
      older men with higher BMI, but only significant among men 20-45 years old, with
      an odds ratio of 2.74 (95% confidence interval 1.1-6.8). The prevalence of ED was
      higher among the younger obese nonsmokers than obese smokers. Premature
      ejaculation, retarded ejaculation, and sexual desire disorders were all unrelated
      to overweight or obesity. CONCLUSION: Obesity (BMI > or = 30 kg/m(2)) seems
      associated with ED among younger men aged 20-45 years. Health programs directed
      toward preventing obesity in younger men may benefit from informing about an
      almost three-fold occurrence of erectile dysfunction associated with obesity.

PMID- 18624964
TI  - The endocrinology of the reproductive years.
AB  - INTRODUCTION: The relationship between reproductive physiology and reproductive
      behavior, a central theme in Professor Lorraine Dennerstein's career, is complex
      but presumably serves to optimize human reproduction. AIM: To review the
      endocrinology of the reproductive years and significant work by Professor
      Dennerstein relating that endocrinology with reproductive behavior. METHODS/MAIN
      OUTCOME MEASURES: Published works of reproductive endocrinology by Professor
      Dennerstein. RESULTS: An exquisitely controlled signaling loop between the
      ovaries and the hypothalamus and pituitary in the brain represents the overlay of
      a dynamic neuroendocrine system on a responsive but ultimately decaying gonadal
      system. The most visible hallmark of this elegant interplay is the menstrual
      cycle, with coordinated hormone patterns directing the maturation and release of
      oocytes, and either supporting an early pregnancy or resetting the system for the
      next cycle. The recognition that these hormone patterns, or their perturbation,
      are related to psychosocial behaviors is reflected in Professor Dennerstein's
      earliest writings relating sex steroids to sexual behavior and menstrual cycles
      to affect, leading to studies describing psychological symptoms in the
      premenstrual syndrome (PMS). These were followed by clinical trials of progestins
      for PMS with conflicting results, and an emerging interest in measuring
      endogenous hormones in that disorder. Her study of reproductive hormones across
      the menstrual cycle in women with PMS definitively refuted the theory that
      deficient progesterone secretion was the etiology of cyclic symptoms. Extension
      of that work demonstrated the cyclic pattern of sexual behavior, but the absence
      of a defined relationship with measured sex steroid patterns. Her interest in the
      effect of age on menstrual cyclicity evolved into her landmark work on the
      menopausal transition, the ultimate result of ovarian gamete depletion and
      absolute loss of spontaneous reproductive capacity. CONCLUSION: Professor
      Dennerstein clearly demonstrated that reproductive behavior is related to
      reproductive physiology, and can be measured and quantified.

PMID- 18624965
TI  - Acute hepatitis associated with treatment of Peyronie's disease with potassium
      para-aminobenzoate (Potaba).
AB  - INTRODUCTION: Potassium para-aminobenzoate is an agent used in the treatment of
      sclerotic diseases including Peyronie's disease of the penis. It has been
      reported that this medication may have been responsible for cases of acute liver
      injury. AIM: To inform clinicians of the possibility of an adverse drug event
      associated with the oral intake of potassium para-aminobenzoate by reporting an
      additional case and compiling information from previous reports. METHODS: The
      affected patient's medical records were diligently reviewed; all available and
      relevant information pertaining to this adverse event is reported. Similar case
      reports were analyzed and compared, and relevant information was compiled in this
      report. RESULTS: The patient enjoyed a full biochemical recovery from his
      hepatitis 4 months after discontinuation of potassium para-aminobenzoate.
      CONCLUSION: To date, the oral use of potassium para-aminobenzoate has been
      reported to be linked to acute liver injury in six individuals. Appropriate
      management of this adverse drug event is the immediate discontinuation of the
      offending drug and general patient support measures.

PMID- 18624967
TI  - Tramadol for premature ejaculation.

PMID- 18624968
TI  - Measurement of the thickness of the urethrovaginal space in women with or without
      orgasm: a rebuttal.

PMID- 18624969
TI  - Shaeer's corporal rotation for length-preserving correction of penile curvature:
      modifications and 3-year experience.
AB  - INTRODUCTION: Correction of penile curvature by corporal rotation enabled the
      correction of 90 degrees ventral curvature with neither shortening nor erectile
      dysfunction. However, some limitations were described, and only one case was
      reported upon. AIM: This work described a 3-year experience with corporeal
      rotation, the modifications addressing and eliminating its drawbacks and
      limitations, as well as the long-term follow-up of 22 patients. METHODS: Modified
      corporeal rotation was performed in 22 patients with various degrees of
      curvature. Degree of deviation, erect penile length, symmetry, and erectile
      function were evaluated and compared pre- and postoperatively. MAIN OUTCOME
      MEASURES: Correction of curvature, resultant sexual function, penile length, and
      girth. RESULTS: Full correction of curvature was achieved in 20 out of 22
      patients, with no shortening, asymmetry, or erectile dysfunction. Residual
      curvature in two patients was no more than 10 degrees. CONCLUSIONS: Corporal
      rotation can restore straightness to the penis with no loss in phallic length,
      asymmetry, or erectile dysfunction. While a variety of surgical techniques are
      feasible for the correction of milder degrees of curvature, we believe that
      severe degrees should be spared the shortening and corrected by corporeal
      rotation.

PMID- 18624970
TI  - Implantation of penile prosthesis in cases of corporeal fibrosis: modified
      Shaeer's excavation technique.
AB  - INTRODUCTION: Implantation of penile prosthesis in case of corporeal fibrosis
      poses a greater risk of complications because of the blinded aggression involved.
      Penoscopic excavation and ultrasonography-guided excavation can decrease these
      complications but still have limitations. AIM: This work described the
      combination of penoscopy-guided and ultrasound-guided excavation in a trial to
      eliminate the limitations inherent to both. METHODS: Twelve patients with penile
      fibrosis were operated upon. A guide wire was inserted under ultrasound
      monitoring, along which penoscopic corporotomy and resection was performed.
      Ultrasound was also used to monitor penoscopic excavation toward the tip of the
      corpus cavernosum and crus. MAIN OUTCOME MEASURES: Ease of the procedure, safety,
      extent of dilatation, and girth of prosthesis implanted. RESULTS: The procedure
      was relatively easy. Ten cases were dilated up to size 13.5 Hegar, and two up to
      size 14. Size 13 prosthesis was implanted in all cases. CONCLUSIONS: The relative
      safety of the procedure, the low incidence of complications, the possibility of
      restoring length and girth to an extent, and the resultant generous dilatation of
      the corpora for accommodating a sizable unhindered inflatable penile prosthesis
      all make ultrasound-guided penoscopic corporotomy and resection a valid option
      for prosthesis implantation in cases of penile fibrosis.

PMID- 18624971
TI  - The erection hardness score and its relationship to successful sexual
      intercourse.
AB  - INTRODUCTION: The Erection Hardness Score (EHS), recently validated, was
      developed in 1998 as a simple (one-item) method to quantify erection outcome
      data. Although it is intuitive that erection hardness and successful sexual
      intercourse (SSI) are related, the link has not been directly established.
      OBJECTIVE: To evaluate the relationship between erection hardness (assessed by
      EHS) and SSI, establishing the EHS as a clinically useful tool. METHODS: The data
      set (N = 307) was from a multinational, double-blind, placebo-controlled trial
      (with open-label extension) of sildenafil citrate in men with erectile
      dysfunction. MAIN OUTCOME MEASURES: Event-based modeling used every intercourse
      attempt and the EHS to estimate the odds ratio of SSI between adjacent EHS
      categories. Mean-based modeling used mean EHS per patient to determine its
      relationship to percentage of SSI. Mediation-based modeling used mean EHS and
      mean percentage of SSI over the double-blind phase to estimate the direct effect
      of sildenafil treatment on SSI and the indirect effect of sildenafil treatment on
      SSI via erection hardness. RESULTS: The odds of SSI for EHS 3 (hard enough for
      penetration but not completely hard) were 41.9 times (95% confidence interval
      [CI], 33.0-53.2; P < 0.0001) that for EHS 2 (hard but not hard enough for
      penetration), and the odds of SSI for EHS 4 (completely hard and fully rigid)
      were 23.7 times (95% CI, 19.5-28.9; P < 0.0001) that for EHS 3. The percentage of
      SSI increased approximately curvilinearly with the increase in mean EHS, from
      almost 60% at EHS 3 to 78.5% at EHS 3.5 and to 93.1% at EHS 4. The indirect
      effect of sildenafil treatment on SSI via erection hardness accounted for almost
      90% of the total effect on SSI (P < 0.0001). CONCLUSION: The close and direct
      relationship between erection hardness and SSI supports the broader use of the
      EHS-a simple, valid, reliable, and responsive measure-in clinical practice.

PMID- 18624972
TI  - Effects of testosterone undecanoate administered alone or in combination with
      letrozole or dutasteride in female to male transsexuals.
AB  - INTRODUCTION: Testosterone undecanoate (TU) has potential as androgen therapy for
      ovariectomized female to male (FtM) transsexual subjects; however, the long-term
      physiologic effects of TU treatment, the significance of testosterone (T), and
      the T metabolites dihydrotestosterone (DHT) and estradiol (E) on specific outcome
      parameters are currently unknown. AIM: The aim of this study was to investigate
      the long-term treatment of TU with regard to bone metabolism, body composition,
      and lipid profile in FtM subjects, and to evaluate the relationship between
      observed effects and circulating levels of T, E, and DHT. MAIN OUTCOME MEASURES:
      Circulating follicle-stimulating hormone, luteinizing hormone, T, E, DHT, and
      lipid concentrations were measured, as well as bone metabolism, body composition,
      and insulin resistance. METHODS: This was a 1-year, randomized treatment, open
      label, uncontrolled safety study. Fifteen ovariectomized FtM subjects from an
      outpatient clinic were divided into three groups to receive TU 1,000 mg alone or
      in combination with oral administration of letrozole (L) 2.5 mg/die or
      dutasteride (D) 0.5 mg/die for a period of 54 weeks. RESULTS: TU alone and TU + D
      treatments were successful in terms of hormone adjustment, did not result in any
      adverse effects, and were well-tolerated. Bone mineral density decreased by an
      average of 0.9 g/cm(2) in the TU + L group, and the addition of D resulted in a
      failure to gain lean mass. CONCLUSIONS: This study confirmed that TU is a
      successful and safe treatment for FtM subjects. These data indicate that E has an
      important role in bone metabolism and that DHT may play a role in muscle
      metabolism.

PMID- 18624973
TI  - Treatment of dyspareunia by creation of a pseudojoint in rigid bone following
      total penile reconstruction with fibular osteocutaneous flap.
AB  - INTRODUCTION: Gender reassignment requires total penile reconstruction, which is
      commonly performed with autologous tissue. One option for reconstruction is the
      free fibula osteocutaneous flap, which provides a long segment of vascularized
      bone that is less susceptible to infection and allows for deep penetration into
      the vagina during sexual intercourse. One problem, however, is that their sexual
      partner may suffer from pain (dyspareunia) because of the long and rigid bone.
      AIMS: Our intent is to elucidate the treatment of female dyspareunia by
      surgically modifying the reconstructed penis with segmental osteotomies and
      fascia interposition within the rigid bone stock resulting from gender
      reassignment with a free fibula osteocutaneous flap. METHODS: In order to improve
      their sexual relations and alleviate dyspareunia, a semirigid penis was created
      by forming a pseudojoint at the junction of the proximal and distal third of the
      fibula bone stock with osteotomies and fascia interposition. MAIN OUTCOME
      MEASURES: Alleviation of dyspareunia by surgical modification of a previously
      reconstructed penis for the couple to continue to have sexual relations. RESULTS:
      The created pseudojoints in the reconstructed penis allowed for pain-free vaginal
      intercourse between the patient and his wife because of its now semirigid
      structure. CONCLUSIONS: The surgical modification presented in this case report
      addresses the treatment of dyspareunia by creating a more malleable penile
      reconstruction, which will now allow for a pain-free vaginal intercourse.

PMID- 18624974
TI  - Erectile dysfunction among men with diabetes is strongly associated with
      premature ejaculation and reduced libido.
AB  - INTRODUCTION: Among men with diabetes, little attention has been given to
      premature ejaculation (PE), reduced libido, and their associations with erectile
      dysfunction (ED), despite the presence of physical and psychologic factors that
      could predispose to all three. AIM: To estimate the prevalence and inter
      associations of ED, PE, and reduced libido among diabetic men and to describe the
      associated clinical, socioeconomic, and lifestyle parameters. METHODS: Cross
      sectional observational study of 253 men with type 2 diabetes randomly selected
      from a clinic in Colombo, Sri Lanka. MAIN OUTCOME MEASURES: Erectile function was
      assessed using the five-item version of the International Index of Erectile
      Function scale. The presence of PE, reduced libido, sociodemographic, and
      lifestyle data was obtained using an interviewer-administered questionnaire.
      Clinical data were obtained from relevant physical examination, patient records,
      and laboratory tests, which included glycosylated hemoglobin, serum cholesterol,
      serum creatinine, and electrocardiogram. RESULTS: One hundred and eighty-five
      (73.1%) of the individuals had some degree of ED, while 84 (33.2%) had severe to
      complete ED. After excluding men with complete ED, the prevalence of PE was 68
      (40.2%). The overall prevalence of reduced libido was 64 (25%). In the
      multivariate analysis, the strongest associations with ED were PE (odds ratio
      [OR] = 4.41, 95% confidence interval [CI] = 2.08-9.39) and reduced libido (OR =
      4.38, CI = 1.39-13.82) followed by lower income (OR = 2.16, CI = 1.32-3.52),
      advancing age (OR = 2.06, CI = 1.44-2.95), and duration of diabetes (OR = 1.48,
      CI = 1.09-2.01). In addition, ED was univariately associated with lower
      educational level (P = 0.05), the presence of hypertension (P = 0.005), and no
      alcohol intake (P = 0.001). The only significant association of PE was the
      severity grade of ED. Associations of reduced libido in the multivariate analysis
      were ED (OR=1.61, CI = 1.23-2.70), advancing age (OR = 1.7, CI = 1.4-2.2), and
      absence of masturbation (OR = 3.3, CI = 1.2-8.8). CONCLUSIONS: ED was strongly
      associated with PE and reduced libido. Diabetic patients presenting with one of
      these three conditions should be screened for the other two.

PMID- 18624975
TI  - A snake venom metalloproteinase, kistomin, cleaves platelet glycoprotein VI and
      impairs platelet functions.
AB  - BACKGROUND AND OBJECTIVES: Injuries to the vessel wall and subsequent exposure of
      the matrix of the subendothelial layer resulted in thrombus formation. Platelet
      glycoprotein (GP) Ib and VI play a crucial role in matrix-induced activation and
      aggregation of platelets. METHODS AND RESULTS: In the present study, we reported
      that the GPIb-cleaving snake venom metalloproteinase (SVMP), kistomin, inhibited
      collagen-induced platelet aggregation. Moreover, kistomin inhibited platelet
      aggregation induced by convulxin (CVX, a GPVI agonist) and a GPVI-specific
      antibody in a concentration and time-dependent manner. Kistomin treatment
      decreased platelet GPVI but not integrin alpha2beta1 and alphaIIbbeta3,
      accompanied with the formation of GPVI cleavage fragments, as determined by flow
      cytometric and Western blot analyses. In addition, intact platelet GPVI and
      recombinant GPVI were digested by kistomin to release 25- and 35-kDa fragments,
      suggesting that kistomin cleaved GPVI near the mucin-like region. We designed
      four synthetic peptides ranging from Leu180 to Asn249 as the substrates for
      kistomin and found that kistomin cleaved these synthetic peptides at
      FSE205/A206TA and NKV218/F219TT, as analyzed by MALDI-TOF-MS. In addition, GPVI
      specific antibody-induced tyrosine kinase phosphorylation in platelets was
      reduced after kistomin pretreatment, and platelet adhesion to collagen but not to
      fibrinogen was attenuated by kistomin. CONCLUSIONS: We provided here the first
      evidence that a P-I snake venom metalloproteinase, kistomin, inhibits the
      interaction between collagen and platelet GPVI through its proteolytic activity
      on GPVI, thus providing an alternative strategy for developing new anti
      thrombotic agents.

PMID- 18624976
TI  - Mild hyperhomocysteinemia is associated with increased TAFI levels and reduced
      plasma fibrinolytic potential.
AB  - BACKGROUND: Mild hyperhomocysteinemia (HHcy) has been shown to be associated with
      impaired fibrinolysis, but some aspects of this association are unclear.
      OBJECTIVE: Using an in vitro model of physiological relevance, we investigated
      whether and how HHcy influences plasma fibrinolytic potential. PATIENTS/METHODS:
      We studied 176 patients with previous venous thromboembolism, 58 with HHcy, 118
      with normal total homocysteine (tHcy) levels (NHcy), at least 3 months after
      withdrawal of anticoagulant therapy. Plasma fibrinolytic potential was measured
      as the fibrinolysis time of tissue factor (TF)-induced clots exposed to 15 ng mL(
      1) t-PA. RESULTS: Fibrinolysis time was longer in HHcy than in NHcy patients, but
      this difference disappeared when the assay was performed in the presence of the
      TAFIa inhibitor, PTCI. Plasma levels of thrombin activatable fibrinolysis
      inhibitor (TAFI) and factor VIII (FVIII) were higher in HHcy than NHcy, whereas
      PAI-1, fibrinogen and endogenous thrombin potential were similar. Using
      multivariate analysis, plasma tHcy was identified as an independent predictor of
      fibrinolysis time. Experiments in which native fibrinogen was replaced by
      purified fibrinogen suggested that alterations of fibrinogen structure did not
      contribute appreciably to the hypofibrinolysis of HHcy plasma samples. The acute
      increase of tHcy either in vivo (after an oral methionine load) or in vitro
      (after incubation of normal plasma with 0.5 mm DL-Hcy) had no effects on
      fibrinolysis or TAFI levels. CONCLUSIONS: We describe an enhanced TAFI-related
      antifibrinolytic activity in mild HHcy, which might account for the reported
      heightened thrombosis risk; however, it is unknown whether HHcy is causally
      related to hypofibrinolysis or an associated bystander.

PMID- 18624977
TI  - Cellular origin of microparticles exposing tissue factor in cancer: a mixed
      double?

PMID- 18624978
TI  - Sequence variants and haplotypes of the factor IX gene and the risk of venous
      thrombosis.

PMID- 18624979
TI  - DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo
      pharmacological profiles.
AB  - BACKGROUND: Factor Xa (FXa), a key serine protease that converts prothrombin to
      thrombin in the coagulation cascade, is a promising target enzyme for the
      prophylaxis and treatment of thromboembolic diseases. DU-176b is a novel
      antithrombotic agent that directly inhibits FXa activity. OBJECTIVE: To evaluate
      the in vitro pharmacological profiles and in vivo effects of DU-176b in animal
      models of thrombosis and bleeding. METHODS: In vitro, FXa inhibition, specificity
      and anticoagulant activities were examined. Oral absorption was studied in rats
      and cynomolgus monkeys. In vivo effects were studied in rat and rabbit models of
      venous thrombosis and tail bleeding. RESULTS: DU-176b inhibited FXa with Ki
      values of 0.561 nm for free FXa, 2.98 nm for prothrombinase, and exhibited >10
      000-fold selectivity for FXa. In human plasma, DU-176b doubled prothrombin time
      and activated partial thromboplastin time at concentrations of 0.256 and 0.508
      microm, respectively. DU-176b did not impair platelet aggregation by ADP,
      collagen or U46619. DU-176b was highly absorbed in rats and monkeys, as
      demonstrated by more potent anti-Xa activity and higher drug concentration in
      plasma following oral administration than a prototype FXa inhibitor, DX-9065a. In
      vivo, DU-176b dose-dependently inhibited thrombus formation in rat and rabbit
      thrombosis models, although bleeding time in rats was not significantly prolonged
      at an antithrombotic dose. CONCLUSIONS: DU-176b is a more potent and selective
      FXa inhibitor with high oral bioavailability compared with its prototype, DX
      9065a. DU-176b represents a promising new anticoagulant for the prophylaxis and
      treatment of thromboembolic diseases.

PMID- 18624980
TI  - Effect of tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a
      rat model of thrombosis.
AB  - OBJECTIVE: To assess the antithrombotic and profibrinolytic effects of
      tiplaxtinin (PAI-039), an orally bioavailable antagonist of PAI-1, in rat models
      of thrombosis. METHODS AND RESULTS: Carotid artery and vena cava vascular injury
      was produced by application of FeCl3 and blood flow was monitored using
      ultrasonic technology. To assess efficacy in a thrombosis prevention paradigm,
      PAI-039 was administered orally 90 min before injury (1-30 mg kg(-1)). To assess
      efficacy in a thrombosis treatment paradigm, vascular injury and stable thrombus
      formation were followed 4 h later by recovery and PAI-039 administration. PAI-039
      prevented carotid artery occlusion in 20, 68 and 60% of animals pretreated with
      0.3, 1.0 and 3.0 mg kg(-1), respectively. Time to occlusive thrombosis was
      increased from 18.2 +/- 4.6 min in controls to 32.5 +/- 8.7 (P = ns), 46.1 +/-
      7.0 (P < 0.05), and 41.6 +/- 11.3 min (P < 0.05) in the respective PAI-039
      treatment groups. In the vena cava protocol, PAI-039 pretreatment significantly
      reduced thrombus weight at PAI-039 doses of 3, 10 and 30 mg kg(-1). When PAI-039
      was dosed in a treatment paradigm 4 h after stable arterial and venous
      thrombosis, a significant reduction in thrombus weight was observed 24 h later at
      PAI-039 doses of 3, 10 and 30 mg kg(-1). PAI-039 (10, 30 and 100 mg kg(-1)) had
      no effect on platelet aggregation in response to ADP or collagen and was not
      associated with increased bleeding or prolonged prothrombin time. In animals
      bearing no vascular injury, PAI-039 had no effect on circulating, low-levels of
      PAI-1 activity. In contrast, circulating PAI-1 activity increased 5-fold
      following the induction of vascular injury, which was completely neutralized by
      PAI-039. CONCLUSIONS: PAI-039 exerts antithrombotic efficacy in rat models of
      arterial and venous vascular injury without effecting platelet aggregation.

PMID- 18624981
TI  - Activated thrombin-activatable fibrinolysis inhibitor is generated in vivo at
      levels that can substantially affect fibrinolysis in chimpanzees in response to
      thrombin generation.

PMID- 18624982
TI  - Activity and regulation of glycoPEGylated factor VIIa analogs.
AB  - BACKGROUND: Recombinant coagulation factor VIIa (rFVIIa) has proven to be a safe
      and effective drug for treatment of bleeding episodes in hemophilic patients with
      inhibitors. However, rFVIIa is cleared from the circulation relatively quickly.
      Protein modification with poly(ethylene glycol) (PEG) can prolong the circulatory
      lifetime of proteins but it could also impair protein function by molecular
      shielding of the protein surface. OBJECTIVES: To characterize the interaction of
      glycoPEGylated rFVIIa - rFVIIa-10K PEG and rFVIIa-40K PEG - with tissue factor
      (TF), factor X (FX) and plasma inhibitors, tissue factor pathway inhibitor (TFPI)
      and antithrombin (AT). METHODS: The amidolytic and FX activation assays were
      employed to investigate the interaction of glycoPEGylated rFVIIa with its
      macromolecular substrate and inhibitors. RESULTS: Both the glycoPEGylated rFVIIa
      analogs exhibited similar amidolytic activity as that of rFVIIa in the absence or
      the presence of relipidated TF. The analogs were as effective as rFVIIa in
      activating FX in the absence of TF. In the presence of TF, the glycoPEGylated
      rFVIIa variants, relative to rFVIIa, were slightly less effective at lower
      concentrations, but no significant differences were found among them in
      activating FX at saturating concentrations. Both AT/heparin and TFPI effectively
      inhibited the glycoPEGylated rFVIIa bound to relipidated TF or TF on stimulated
      endothelial cells. In contrast to their normal interaction with TF, the
      glycoPEGylated rFVIIa variants appeared to interact poorly with phospholipids.
      CONCLUSIONS: The glycoPEGylated rFVIIa variants retained their catalytic activity
      and interacted efficiently with TF, FX and the plasma inhibitors. Further work
      with appropriate in vitro and in vivo model systems is needed to determine the
      feasibility of using glycoPEGylated rFVIIa to improve therapeutic options for
      bleeding disorders.

PMID- 18624983
TI  - The relationship between unprovoked venous thromboembolism, age, and acute
      myocardial infarction.
AB  - BACKGROUND: Patients with unprovoked venous thromboembolism (VTE) may be at
      increased risk of acute myocardial infarction (AMI). However, the nature and
      clinical significance of this association remain unclear, particularly as it
      relates to age of presentation. METHODS: We performed a longitudinal matched
      cohort study utilizing multiple administrative databases. Ontario residents aged
      20-64 years diagnosed with unprovoked VTE from 1 April 1991 to 31 March 1995 (n =
      6065) were matched to a population cohort (n = 12 040) in 1 : 2 fashion on the
      basis of age, gender, socioeconomic class, cardiovascular risk factors and other
      comorbidities. The primary outcome was a comparison of relative risk of AMI over
      10-year follow-up in subjects with unprovoked VTE (overall and stratified by age)
      vs. controls. Secondary outcomes included risk of death or the composite endpoint
      of AMI and/or death. RESULTS: Patients 20-39 years of age presenting with
      unprovoked VTE had an increased risk of AMI [adjusted hazard ratio (HR) 3.92, 95%
      confidence interval (CI) 1.65-9.35] as compared to controls; the association was
      applicable to those without atherosclerotic risk factors at baseline. There was
      no significant relationship between unprovoked VTE and AMI among patients 40-64
      years old, with or without atherosclerotic risk factors. Irrespective of age,
      patients with unprovoked VTE had an increased risk of all-cause death or our
      composite endpoint of AMI and/or death as compared to patients without VTE.
      CONCLUSIONS: Unprovoked VTE is associated with a nearly 4-fold higher risk of
      subsequent AMI among younger patient populations. Future studies must explore the
      risk-benefit tradeoffs of long-term surveillance and management options among
      such patient populations.

PMID- 18624984
TI  - Correlation between the histopathological diagnosis by AgNOR count and AgNOR area
      in canine mammary tumors.
AB  - BACKGROUND: Mammary tumors are the most common type of tumor in female dogs. The
      histopathological diagnosis is usually made by a hematoxylin-eosin (HE) staining
      of the tumor, which then requires a pathologist's judgment for assessment of
      malignancy. The purpose of this study was to investigate an alternative silver
      staining of some argyrophilic nucleolar organizer regions (AgNOR) for improving
      the diagnostic accuracy with mammary tumors. HYPOTHESIS: There is a correlation
      between the histopathological diagnosis by AgNOR count and AgNOR area in canine
      mammary tumors. ANIMALS: Seventy-three canine mammary tumors from 33 female dogs.
      MATERIALS AND METHODS: The AgNOR staining was evaluated retrospectively in 73
      canine mammary tumors with a parallel HE staining as a "Gold Standard." Both a
      quantitative manual counting method and a qualitative computerized morphometric
      method were tested. RESULT: The result from both methods indicated a clinically
      relevant difference in the mean values of the AgNOR in the following 4
      categories: malignant, benign, hyperplastic, and normal mammary tissue. The
      counting method was superior, with 89% of the cases given a correct diagnosis of
      a malignant or a nonmalignant canine mammary tumor. The 2 methods were then
      compared to test their ability to classify the tumors correctly. Again, the
      counting method was the most reliable method, with a sensitivity of 80% and a
      specificity of 76% when the upper 50% of the AgNOR counts were presumed
      malignant. CONCLUSION AND CLINICAL IMPORTANCE: The results indicated that an
      AgNOR test could be an aid to pathologists as a prognostic indicator or to assist
      them in deciding between a benign or a malignant diagnosis in questionable cases.

PMID- 18624985
TI  - Plasma membrane damage to Candida albicans caused by chlorine dioxide (ClO2).
AB  - AIM: To investigate the plasma membrane damage of chlorine dioxide (ClO(2)) to
      Candida albicans ATCC10231 at or below the minimal fungicidal concentration
      (MFC). METHODS AND RESULTS: ClO(2) at MFC or below was adopted to treat the cell
      suspensions of C. albicans ATCC10231. Using transmission electron microscopy, no
      visible physiological alteration of cell shape and plasma membrane occurred.
      Potassium (K(+)) leakages were significant; likewise, it showed time- and dose
      dependent increases. However, adenosine triphosphate (ATP) leakages were very
      slight. Research shows that when 99% of the cells were inactivated, the leakage
      was measured at 0.04% of total ATP. Compared with the mortality-specific
      fluorescent dye of DiBAC(4)(3), majority of the inactivated cells were poorly
      stained by propidium iodide, another mortality-specific fluorescent dye which can
      be traced by flow cytometry. CONCLUSION: At or below MFC, ClO(2) damages the
      plasma membranes of C. albicans mainly by permeabilization, rather than by the
      disruption of their integrity. K(+) leakage and the concomitant depolarization of
      the cell membrane are some of the critical events. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These insights into membrane damages are helpful in understanding the
      action mode of ClO(2).

PMID- 18624986
TI  - Coronary artery bypass in myocardial ischemia of the young due to hydatid cyst.
AB  - Cardiac hydatid cyst is an uncommon disease, especially in France. It is rarely
      responsible for myocardial ischemia, and even more rarely in the young. We report
      the clinical features and imaging of a 24-year-old Tunisian woman with hydatid
      cyst of the free wall of the left ventricle responsible for myocardial ischemia,
      associated with a hepatic hydatid cyst. Management consisted of a combination of
      surgery with cystopericystectomy and coronary artery bypass graft and prolonged
      medical treatment as for treatment of hepatic hydatid cyst. Three-year follow-up
      revealed no recurrence. This case illustrates two interesting points: the rare
      clinical presentation of cardiac hydatid cyst with a coronary syndrome in a young
      24-year-old woman related to compression of the left anterior descending artery
      by the cyst with a need for coronary artery bypass graft after resection of the
      cyst, and the value of medical treatment of hydatid disease, even for cardiac
      localization.

PMID- 18624988
TI  - Growth hormone treatment in short children with chronic kidney disease.
AB  - Growth hormone (GH) has been used for treatment of impaired growth in children
      with chronic kidney disease (CKD) for nearly 17 years. Controlled and open-label
      studies have shown that GH is highly effective in improving growth velocity and
      adult height. The growth response is negatively correlated with age and height at
      start and time spent on dialysis treatment; it is positively correlated with dose
      and duration of treatment and the primary renal disease (renal hypodysplasia). In
      children with renal transplants, corticosteroid treatment is an additional factor
      negatively influencing spontaneous growth rates. However, GH treatment is able to
      compensate corticosteroid-induced growth failure. GH treatment improved final
      height by 0.5-1.7 standard deviation score (SDS) in various studies, whereas the
      control group lost about 0.5 SDS in comparable time intervals. These variable
      results are explained in part by the factors mentioned above. The adverse events
      are comparable to those in non-CKD children treated with GH. CONCLUSION: GH
      treatment is safe and highly effective in improving growth and final height of
      short children with all stages of CKD. The highest treatment success is obtained
      if treatment is started at an early age and with relatively well-preserved
      residual renal function and continued until final height.

PMID- 18624987
TI  - The fate of ductus arteriosus in infants at 23-27 weeks of gestation: from
      spontaneous closure to ibuprofen resistance.
AB  - BACKGROUND: Some extremely preterm infants experience spontaneous closure of the
      ductus arteriosus. On the other side, a high percentage (22-30%) of preterm
      infants born at the lower gestational age fail to respond to a single course of
      ibuprofen. AIM: To assess if there are clinical characteristics effective as
      predictive factors for spontaneous closure of the ductus arteriosus, development
      of patent ductus arteriosus (PDA) and ibuprofen-resistant PDA. METHODS: A cohort
      of inborn infants less than 28 weeks of gestation were prospectively studied. We
      distinguished infants who had spontaneous closure of ductus arteriosus, who
      developed PDA and who developed ibuprofen-resistant PDA. RESULTS: We studied 34
      infants. Eight infants (24%) had spontaneous closure of PDA, 17 infants (50%) had
      a closure of PDA following the first ibuprofen course, while 9 infants (26%)
      failed to respond to the first ibuprofen course. Infants born at 23-25 weeks of
      gestation were found to have lower likelihood of PDA spontaneous closure, and
      higher risk of developing PDA refractory to ibuprofen therapy. Sepsis was found
      to increase significantly the risk of ibuprofen failure in closing PDA.
      CONCLUSION: An important percentage of extremely preterm infants exhibited
      spontaneous closure of PDA. Among clinical characteristics lowest gestational
      ages predict PDA and ibuprofen-resistant PDA, while sepsis predicts only
      ibuprofen-resistant PDA.

PMID- 18624989
TI  - Taller stature after postnatal rapid weight gain in early infancy predicts
      overweight status at age 3.
AB  - AIM: To evaluate whether postnatal rapid weight gain in early infancy is
      associated with subsequent tall stature and being overweight at age 3, and taller
      stature after postnatal rapid weight gain predicts overweight status at age 3.
      METHODS: Data from a retrospective cohort study (time period 2003-2004, total
      number = 1353 subjects in Kumamoto, Japan) were used. The rate of weight gain
      during the first 3-4 months was calculated as 100 g/month, and postnatal rapid
      and slow growth were calculated by using weight standard deviation (SD).
      Overweight status at 3 years of age was determined according to the definition of
      the International Obesity Task Force. RESULTS: In total, 4.7% of subjects were
      overweight at age 3. Postnatal rapid weight gain, associated with height
      increases until age 3 (p < 0.0001), and the rate of weight gain were significant
      risk factors for being overweight in children at age 3. Taller heights at 6-9
      months and 17-20 months of age following postnatal rapid weight gain were
      associated with overweight status at age 3 (p < 0.05). CONCLUSION: Taller stature
      following postnatal rapid weight gain in early infancy predicts overweight status
      at age 3; additionally, rapid infancy weight gain contributes to the acceleration
      of statural growth in overweight children.

PMID- 18624990
TI  - Drink driving and the patterns and context of drinking among New Zealand
      adolescents.
AB  - AIM: To examine the association between drink driving and the patterns and
      locations of usual drinking among New Zealand adolescents. METHODS: This is a
      secondary analysis of data from a nationally representative youth health survey,
      the sampling frame for which was all New Zealand secondary schools with more than
      50 students enrolled in years 9 to 13 (ages 12 to 18 years) in 2001. The analysis
      was restricted to the 3408 survey respondents aged 15 years or older who were
      current drinkers and drivers. RESULTS: In total, 17.3% of participants reported
      drink driving in the previous month. Drink driving was significantly associated
      with frequent (at least weekly) alcohol use, binge drinking and usually drinking
      away from home, that is in cars, outdoors, at bars or nightclubs, at parties, at
      school and at work. Students' perception that parents and schools care about
      them, parental monitoring, and high academic achievement was associated with a
      reduced risk of drink driving while having friends who drink alcohol increased
      this risk. These associations were similar among boys and girls. CONCLUSION: The
      findings support calls to address how and where young people drink, and indicate
      the potential gains to be made with family- and school-based interventions.

PMID- 18624991
TI  - Academic achievement, behavioural outcomes and MRI findings at 15 years of age in
      very low birthweight children.
AB  - AIM: To assess cognitive, academic and behavioural functions in 15-year-old very
      low birthweight (VLBW) children and relate results to gender, neonatal risk
      factors, growth and magnetic resonance imaging (MRI) findings. METHODS: Sixty-one
      out of 86 VLBW children and 57/86 term controls born in the south-east region of
      Sweden were assessed regarding cognition (WISC III), school outcome, behaviour
      and growth. VLBW children were examined using cerebral MRI. RESULTS: VLBW
      children performed significantly lower than their term controls on WISC III and
      49% had IQ lower than 85. Ten VLBW children with IQ < 70 had not been clinically
      identified earlier and a majority of these children attended mainstream school.
      VLBW girls had significantly lower total problems scores. Using MRI, white matter
      damage (WMD) was detected in 16 (27%) children. VLBW boys with WMD had
      significantly lower IQ than those without. Small occipito-frontal circumference
      (OFC) correlated with low IQ. Mechanical ventilation and intraventricular
      haemorrhage (IVH) showed significant correlations with lower IQ and reading
      skills. CONCLUSION: VLBW children achieved poorer results compared with their
      controls in cognitive tests. Mechanical ventilation and IVH were related to
      poorer academic outcome. Many of the children with low IQ had not been identified
      earlier. Therefore, we recommend that VLBW children undergo an IQ test before
      beginning school in order to receive adequate support.

PMID- 18624992
TI  - Real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal bacteraemia.
AB  - OBJECTIVE: To evaluate a real-time PCR assay for the diagnosis of neonatal
      bacteraemia. PATIENTS AND METHODS: Two hundred ninety-five plasma samples from
      288 newborns with suspected neonatal sepsis were collected prospectively for the
      purpose of polymerase chain reaction (PCR)-based bacterial detection. A real-time
      PCR targeting the bacterial gene for 16S-rRNA gene combined with four specific
      probes designed to detect Gram-negative bacteria, Staphylococcus aureus and
      coagulase-negative staphylococci (CoNS) was developed. All samples positive in
      the universal PCR were further sequenced for bacterial identification. RESULTS:
      When applied to a material from 50 patients with positive blood culture and 245
      patients with negative blood culture, the universal PCR showed a sensitivity of
      42% (28-57), a specificity of 95% (92-97), a positive predictive value of 64% (45
      80), and a negative predictive value of 89% (84-92) (95% confidence intervals in
      brackets). CONCLUSION: A new real-time PCR technique was for the first time
      applied to a well-defined prospectively and consecutively enrolled material of
      newborns with suspected sepsis, combining the benefits of real-time PCR with
      specific probes and sequencing. The method managed to detect bacteraemia with
      high specificity even though the sensitivity was low. Factors causing the low
      sensitivity are identified and further strategies to develop the method are
      described.

PMID- 18624993
TI  - Incidence rates of asthma, rhinitis and eczema symptoms and influential factors
      in young children in Sweden.
AB  - AIM: To estimate the incidence rates for asthma, rhinitis and eczema symptoms and
      to investigate the importance of different influential factors for the incidence
      of these symptoms. METHODS: The Dampness in Building and Health study commenced
      in the year 2000 in Varmland, Sweden with a parental questionnaire based on an
      ISAAC protocol to all children in the age of 1-6 years. Five years later a follow
      up questionnaire was sent to the children that were 1-3 years at baseline. In
      total, 4779 children (response rate = 73%) participated in both surveys and
      constitute the study population in this cohort study. RESULTS: The 5-year
      incidence of doctor-diagnosed asthma was 4.9% (95% CI 4.3-5.3), rhinitis was 5.7%
      (5.0-6.4) and eczema was 13.4% (12.3-14.5). However, incidence rates strongly
      depend on the health status of the baseline population. Risk factors for incident
      asthma were male gender and short period of breast-feeding. Allergic symptoms in
      parents were also a strong risk factor for incident asthma, as well as for
      rhinitis and eczema. CONCLUSION: When comparing incident rates of asthma between
      different studies it is important to realize that different definitions of the
      healthy baseline population will give rise to different incident rates.

PMID- 18624994
TI  - Human placental IGF-I and IGF-II expression: correlating maternal and infant
      anthropometric variables and micronutrients at birth in the Pakistani population.
AB  - AIM: To correlate infant birth weight with maternal and infant biometric data,
      including the expression of placental IGF-I and IGF-II at birth, and levels of
      serum zinc and ferritin. METHODS: The data consisted of observations from 89
      women from Karachi, Pakistan. Placental and cord blood samples were taken
      immediately following delivery and were subsequently divided into two groups,
      small and large for gestational age (SGA and LGA). RESULTS: The mean birth weight
      was 2.79 kg; the prevalence of SGA being 13.4% (< or =10th percentile); the
      prevalence of LGA being 23.6% (> or =90th percentile). Placental IGF-I and IGF-II
      mRNA expression was greater in the LGA group (p < 0.05). Furthermore, a
      significant correlation was noted between infant birth weight and maternal
      anthropometric parameters (p < 0.01). Cord zinc levels were also significantly
      higher in the LGA group (p < 0.05). CONCLUSION: Maternal anthropometry, along
      with placental IGF-I and IGF-II mRNA levels, correlated significantly with infant
      birth weight suggesting the importance of these growth factors for birth weight
      outcomes. The higher zinc levels in the LGA group also suggest the importance of
      this micronutrient in foetal growth. Our results suggest that growth problems
      have a multifactorial aetiology arising from within the infant rather than due to
      maternal constraint alone.

PMID- 18624996
TI  - Molecular epidemiological and mutational analysis of DNA mismatch repair (MMR)
      genes in endometrial cancer patients with HNPCC-associated familial
      predisposition to cancer.
AB  - Recently, a high rate of endometrial cancer has been reported in women with
      hereditary non-polyposis colorectal cancer (HNPCC), suggesting a relationship
      between familial endometrial cancers and HNPCC. Familial endometrial cancers
      constitute only about 0.5% of all endometrial carcinomas and it is essential to
      examine family histories in detail. A mutational analysis of three DNA mismatch
      repair (MMR) genes (hMLH1, hMSH2 and hMSH6) in patients with endometrial cancer
      who meet our criteria for familial predisposition to HNPCC-associated endometrial
      cancers was performed. Mutations were detected in 18 of the 120 patients (15.0%).
      Most HNPCC-related endometrial cancers do not meet the New Amsterdam Criteria for
      HNPCC. These clinical criteria may identify only some HNPCC-associated
      endometrial cancers. Establishing the correct family history for endometrial
      cancer patients is important for diagnosing familial endometrial carcinomas. An
      analysis of MMR genes may be useful for patients with endometrial cancer showing
      familial aggregation. In addition, gynecologists must be accurately informed, and
      it is important to perform large-scale, multicenter studies both nationwide and
      internationally.

PMID- 18624998
TI  - Impact of adiponectin and ghrelin on incident glucose intolerance and on weight
      change.
AB  - OBJECTIVES: Adiponectin and ghrelin are associated with adiposity and type 2
      diabetes in several studies. We sought to prospectively determine the interaction
      of adiponectin and ghrelin in the development of adiposity and hyperglycaemia.
      DESIGN: Prospective observational study. PARTICIPANTS: 393 community-dwelling
      Afro-Jamaicans (mean age 47 +/- 13 years; BMI 27.3 +/- 6.3 kg/m(2); 63% women)
      without glucose intolerance at baseline. MEASUREMENTS: Anthropometry, fasting
      plasma glucose, 2-h plasma glucose, insulin resistance (HOMA-IR), adiponectin and
      ghrelin concentrations were measured at baseline and 4.1 +/- 0.9 years later.
      Multivariate analyses were used to explore the associations of HOMA-IR,
      adiponectin and ghrelin with weight change and glycaemia. Results The mean weight
      change was 2.6 +/- 5.5 kg. There were 114 incident cases of impaired glucose
      tolerance (IGT) and 35 cases of diabetes mellitus. Adiponectin was positively
      correlated with age and female sex (P-values < 0.01). After adjusting for age and
      sex, adiponectin and ghrelin were significantly correlated with weight at
      baseline and follow-up. However, they were not associated with weight change even
      after further adjustment for baseline weight. Adiponectin, but not ghrelin, was
      associated with 2-h glucose concentrations at follow-up even after adjusting for
      age, sex, HOMA-IR and BMI (P = 0.04). In the fully adjusted logistic regression
      model, adiponectin predicted incident IGT (OR 0.93; 95% CI: 0.87-0.99) and
      attenuated the effect of BMI on incident IGT. CONCLUSIONS: These longitudinal
      data show that adiponectin and ghrelin may not be causally involved in the
      development of obesity. However, adiponectin is independently associated with
      decreased risk of incident IGT.

PMID- 18624999
TI  - The Pro 12 Ala PPAR gamma gene polymorphism: possible modifier of the activity
      and severity of thyroid-associated orbitopathy (TAO).
AB  - OBJECTIVE: The PPAR gamma transcription factor, is involved in both adipogenesis
      and inflammation, which have been implicated in the pathogenesis of thyroid
      associated orbitopathy (TAO). The aim of this study was to explore the
      possibility that the Pro(12)Ala polymorphism of the PPAR gamma gene, associated
      with a modified transcriptional activity, might be affecting the severity of TAO.
      SUBJECTS AND DESIGN: We studied two cohorts of patients with Graves' disease
      (GD): Group 1 comprised 172 patients of Dutch ethnic origin with TAO, who
      attended the outpatients' clinic, Department of Endocrinology and Orbital Centre
      of the Academic Medical Centre, Amsterdam. Group 2 comprised 93 consecutive
      patients with GD of Greek ethnic origin, who did not have TAO. In group 1,
      exophthalmometry measurements, lid oedema, diplopia (n = 172) and clinical
      activity score (CAS) (n = 110), always assessed by the same group of three
      investigators, were recorded. Autoantibody levels were measured. RESULTS: Allele
      frequency was 11.5%. There was no difference in the distribution of the
      polymorphism between GD patients with and without TAO. Among group 1 patients
      proptosis was significantly lower in Pro(12)Ala carriers (20.1 +/- 3.3 vs. 22.1
      +/- 3.1, P = 0.003, t-test). PPAR gamma polymorphism carriers had lower TSH-Rab
      levels (mean rank 61.8 vs. 83.2, P = 0.015) and lower CAS (available in 110
      patients) (mean rank 38.9 vs. 55.4, P = 0.022, M-W-test). The frequency of the
      polymorphism decreased with increasing CAS (P = 0.023 linear by linear
      association). Multivariate analysis (step) showed that the association of either
      proptosis or CAS with the PPAR gamma gene variant remained significant when age,
      smoking and TSH-Rab levels were taken into account (P < 0.01). CONCLUSIONS: The
      distribution of the Pro(12)Ala PPAR gamma gene polymorphism is equally present in
      patients with GD with or without TAO. Among patients with TAO this polymorphism
      is associated with less-severe and less-active disease.

PMID- 18625000
TI  - No difference between strontium ranelate (SR) and calcium/vitamin D on bone
      turnover markers in women with established osteoporosis previously treated with
      teriparatide: a randomized controlled trial.
AB  - Objective To evaluate the effect of strontium ranelate (SR) on bone turnover
      markers in women with established osteoporosis previously treated with
      teriparatide (TPTD--recombinant human PTH 1-34). DESIGN PATIENTS: Twenty-two
      postmenopausal Caucasian women (aged 65.7 +/- 1.7 years) with established
      osteoporosis previously treated with TPTD 20 microg daily for 18 months were
      randomly assigned to receive either SR (SR group, n = 11) or calcium and vitamin
      D (control group, n = 11). MEASUREMENTS: Blood samples for serum N-terminal
      propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen
      (CTx) and total alkaline phosphatase (ALP) were obtained from all women before
      (pre-TPTD) and after (post-TPTD) TPTD administration, as well as 6 months after
      SR or calcium/vitamin D administration (post-SR/Ca). RESULTS: Serum P1NP, CTx and
      total ALP increased significantly after TPTD treatment and decreased at the end
      of the study in both SR and control groups, with no difference between them.
      CONCLUSIONS: SR following TPTD administration acts predominantly as an
      antiresorptive agent with no evidence of additional osteoanabolic action. In this
      setting, SR is not more effective than Ca/vitamin D as far as bone turnover
      markers are concerned.

PMID- 18625001
TI  - MELAS syndrome, diabetes and thyroid disease: the role of mitochondrial oxidative
      stress.

PMID- 18625002
TI  - Rimonabant: a rapidly expanding role in the management of metabolic and systemic
      disorders besides polycystic ovarian syndrome.

PMID- 18625004
TI  - Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting
      among cancer patients: systematic review and meta-analysis.
AB  - This paper aims to evaluate the anti-emetic efficacy of cannabinoids in cancer
      patients receiving chemotherapy using a systematic review of literature searched
      within electronic databases such as PUBMED, EMBASE, PSYCINFO, LILACS, and 'The
      Cochrane Collaboration Controlled Trials Register'. Studies chosen were
      randomized clinical trials comprising all publications of each database until
      December 2006. From 12 749 initially identified papers, 30 fulfilled the
      inclusion criteria for this review, with demonstration of superiority of the anti
      emetic efficacy of cannabinoids compared with conventional drugs and placebo. The
      adverse effects were more intense and occurred more often among patients who used
      cannabinoids. Five meta-analyses were carried out: (1) dronabinol versus placebo
      [n=185; relative risk (RR)=0.47; confidence interval (CI)=0.19-1.16]; (2)
      Dronabinol versus neuroleptics [n=325; RR=0.67; CI=0.47-0.96; number needed to
      treat (NNT)=3.4]; (3) nabilone versus neuroleptics (n=277; RR=0.88; CI=0.72
      1.08); (4) levonantradol versus neuroleptics (n=194; RR=0.94; CI=0.75-1.18); and
      (5) patients' preference for cannabis or other drugs (n=1138; RR=0.33; CI=0.24
      0.44; NNT=1.8). The superiority of the anti-emetic efficacy of cannabinoids was
      demonstrated through meta-analysis.

PMID- 18625005
TI  - Tumour-specific induction of immune complexes: DCP-IgM in hepatocellular
      carcinoma.
AB  - BACKGROUND: In the sera of liver, colorectal and prostate cancer patients,
      several biomarkers may be detected as IgM immune complexes. To determine whether
      the presence of immune complexes was correlated to an increase of IgMs, we
      measured the IgM content in the sera of patients with hepatocellular carcinoma
      (HCC) and cirrhosis, and evaluated the occurrence of des-gamma-carboxy
      prothrombin (DCP) as immune complexes (DCP-IgM) compared to the levels of DCP and
      alpha-fetoprotein (AFP). PATIENTS AND METHODS: Serum samples from 31 patients
      with cirrhosis, 33 untreated HCC patients diagnosed by ultrasound, computed
      tomography and/or magnetic resonance and confirmed by histopathology, when
      indicated, and 30 healthy controls were analysed. Concentrations of IgM and DCP
      IgM were determined by ELISAs. RESULTS: Circulating IgM in patients with HCC
      (median level = 1.79 mg mL(-1)) and cirrhosis (1.09 mg mL(-1)) were not
      significantly different (P = 0.1376) while DCP-IgM were significantly higher in
      HCC patients (median level = 2171.2 AU mL(-1)) than in those with cirrhosis (1152
      AU mL(-1), P = 0.0047). No correlation was found between DCP-IgM and IgM in HCC
      (r = 0.227) and cirrhosis patients (r = 0.475). DPC-IgM was positive in 55%
      (18/33) of HCC patients and in 26% (8/31) of cirrhosis patients compared to 39%
      and 26% for DCP and 48% and 13% for AFP. DCP-IgM, DCP and AFP tests had 100%
      specificity in healthy controls. CONCLUSIONS: DCP-IgM in HCC patients was not
      associated with an increase in IgM concentration. DCP-IgM was more frequently
      detected in HCC patients than DCP and AFP, strengthening the diagnostic role of
      IgM immune complexes for liver cancer.

PMID- 18625006
TI  - A complete inventory of all enzymes in the eukaryotic methionine salvage pathway.
AB  - The methionine salvage pathway is universally used to regenerate methionine from
      5'-methylthioadenosine, a byproduct of certain reactions involving S
      adenosylmethionine. We identified and verified the genes encoding the enzymes of
      all steps in this cycle in a commonly used eukaryotic model system: the yeast
      Saccharomyces cerevisiae. The genes encoding 5'-methylthioribose-1-phosphate
      isomerase and 5'-methylthioribulose-1-phosphate dehydratase are herein named MRI1
      and MDE1, respectively. The 5'-methylthioadenosine phosphorylase was verified as
      Meu1p, the 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase as Utr4p and
      the aci-reductone dioxygenase as Adi1p. The homologue of the enolase/phosphatase
      gene, YNL010w, was excluded from its candidate role in the cycle. The methodology
      used involved auxotrophic growth tests and analysis of intracellular 5'
      methylthioadenosine in deletion mutants. The last step, a transamination of 4
      methylthio-2-oxobutyrate to yield methionine, was found to be a highly redundant
      step. It was catalysed by amino acid transaminases, mainly coupled with aromatic
      and branched chain amino acids as amino donors, but also with proline, lysine and
      glutamate/glutamine. The aromatic amino acid transaminases, Aro8p and Aro9p, and
      the branched chain amino acid transaminases, Bat1p and Bat2p, seemed to be the
      main enzymes exhibiting 4-methylthio-2-oxobutyrate transaminase activity. Bat2p
      was found to be less specific and used proline, lysine, tyrosine and glutamate as
      amino donors in addition to the branched chain amino acids. Thus, for the first
      time, all enzymes of the methionine salvage pathway were identified in a
      eukaryote.

PMID- 18625007
TI  - The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca)
      channels.
AB  - The Janus-faced atracotoxins are a unique family of excitatory peptide toxins
      that contain a rare vicinal disulfide bridge. Although lethal to a wide range of
      invertebrates, their molecular target has remained enigmatic for almost a decade.
      We demonstrate here that these toxins are selective, high-affinity blockers of
      invertebrate Ca(2+)-activated K(+) (K(Ca)) channels. Janus-faced atracotoxin (J
      ACTX)-Hv1c, the prototypic member of this toxin family, selectively blocked K(Ca)
      channels in cockroach unpaired dorsal median neurons with an IC(50) of 2 nm, but
      it did not significantly affect a wide range of other voltage-activated K(+),
      Ca(2+) or Na(+) channel subtypes. J-ACTX-Hv1c blocked heterologously expressed
      cockroach large-conductance Ca(2+)-activated K(+) (pSlo) channels without a
      significant shift in the voltage dependence of activation. However, the block was
      voltage-dependent, indicating that the toxin probably acts as a pore blocker
      rather than a gating modifier. The molecular basis of the insect selectivity of J
      ACTX-Hv1c was established by its failure to significantly inhibit mouse mSlo
      currents (IC(50) approximately 10 mum) and its lack of activity on rat dorsal
      root ganglion neuron K(Ca) channel currents. This study establishes the Janus
      faced atracotoxins as valuable tools for the study of invertebrate K(Ca) channels
      and suggests that K(Ca) channels might be potential insecticide targets.

PMID- 18625008
TI  - Specificity evolution of the ADP-dependent sugar kinase family: in silico studies
      of the glucokinase/phosphofructokinase bifunctional enzyme from
      Methanocaldococcus jannaschii.
AB  - In several archaea of the Euryarchaeota, the glycolytic flux proceeds through a
      modified version of the Embden-Meyerhof pathway, where the phosphofructokinase
      and glucokinase enzymes use ADP as the phosphoryl donor. These enzymes are
      homologous to each other. In the hyperthermophilic methanogenic archaeon
      Methanocaldococcus jannaschii, it has been possible to identify only one homolog
      for these enzymes, which shows both ADP-dependent glucokinase and
      phosphofructokinase activity. This enzyme has been proposed as an ancestral form
      in this family. In this work we studied the evolution of this protein family
      using the Bayesian method of phylogenetic inference and real value evolutionary
      trace in order to test the ancestral character of the bifunctional enzyme.
      Additionally, to search for specificity determinants of these two functions, we
      have modeled the bifunctional protein and its interactions with both sugar
      substrates using protein-ligand docking and restricted molecular dynamics. The
      results show that the evolutionary story of this family is complex. The root of
      the family is located inside the glucokinase group, showing that the bifunctional
      enzyme is not an ancestral form, but could be a transitional form from
      glucokinase to phosphofructokinase, due to its basal location within the
      phosphofructokinase group. The evolutionary trace and the molecular modeling
      experiments showed that the specificity for fructose 6-phosphate is mainly
      related to the stabilization of a negative charge in the phosphate group, whereas
      the specificity for glucose is related to the presence of some histidines instead
      of glutamines/asparagines and to the interaction of this ligand with a glutamic
      acid residue corresponding to Glu82 in the bifunctional enzyme.

PMID- 18625009
TI  - Quercetin but not luteolin suppresses the induction of lethal shock upon
      infection of mice with Salmonella typhimurium.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is important for the induction of
      systemic inflammatory responses that lead to lethal shock. Quercetin and
      luteolin, which differ by one hydroxyl group, are known to suppress the
      lipopolysaccharide-induced production of TNF-alpha in vitro. We show differing
      inhibitory effects of quercetin and luteolin on the induction of lethal shock in
      Salmonella typhimurium aroA-infected mice. In a time- and dose-dependent manner,
      quercetin reduced the plasma levels of TNF-alpha, lowered bacterial titers in
      livers, prevented liver damage and prolonged survival, while luteolin had little
      or no effect. Compared with luteolin, quercetin increased the infiltration of Gr
      1(+)CD69(+) neutrophils into the peritoneal cavity and lowered heat shock protein
      70 expression. Obviously, the additional hydroxyl group in quercetin is important
      for suppressing infection-induced lethal shock in mice.

PMID- 18625010
TI  - VirB type IV secretory system does not contribute to Brucella suis' avoidance of
      human dendritic cell maturation.
AB  - Dendritic cells (DCs), which are critical components of adaptive immunity, are
      highly susceptible to infection with the intracellular bacteria Brucella.
      Infection with living Brucella prevents infected human DCs from engaging in
      maturation processes, thus impairing their capacity to present antigens to naive
      T cells and to secrete IL-12. Recently, we have established that several
      attenuated mutants of Brucella (rough, omp25, bvrR) are unable to control DCs
      maturation and thus effectively stimulate naive T cells, which could be the
      origin of the protective immunity elicited by these mutants in vivo. In this
      study, we investigate the interactions of a VirB-defective Brucella mutant with
      human DCs to determine whether its attenuation could be attributed to the
      induction of an adaptive immune response. We show here that in contrast to
      previously studied strains and similar to wild-type strains, this virB mutant was
      unable to trigger significant DC maturation. Together with recently published
      data describing infection with virB mutants in vivo, these results suggest that
      Brucella T4SS VirB is not involved in the control of DC maturation and does not
      interfere with the establishment of a T-helper type 1 adaptive immune response.

PMID- 18625011
TI  - Serotyping of clinical isolates belonging to Proteus mirabilis serogroup O36 and
      structural elucidation of the O36-antigen polysaccharide.
AB  - The O-specific polysaccharide (OPS) isolated from the lipopolysaccharide of
      Proteus mirabilis O36 was found to have a pentasaccharide repeating unit of the
      following structure: -->2)-beta-D-Ribf-(1-->4)-beta-D-Galp-(1-->4)-alpha-D
      GlcpNAc6Ac-(1-->4)-beta-D-Galp-(1-->3)-alpha-D-GlcpNAc-(1-->. The structure is
      unique among Proteus OPS, which is in agreement with the classification of this
      strain into a separate Proteus O-serogroup. Remarkably, the P. mirabilis O36
      polysaccharide has the same structure as the OPS of Escherichia coli O153, except
      that the latter is devoid of O-acetyl groups. The cross-reaction of anti-O36
      antibodies with the O-part of E. coli O153 lipopolysaccharide is observed. In the
      present study, two steps of serotyping Proteus strains are proposed: screening of
      dry mass with enzyme-linked immunosorbent assay and immunoblot with the crude
      lipopolysaccharides. This method allowed serotyping of 99 P. mirabilis strains
      infecting the human urinary tract. Three strains were classified into serogroup
      O36. The migration pattern of these lipopolysaccharides fraction with long O
      specific PSs was similar to the standard laboratory P. mirabilis O36 (Prk 62/57)
      lipopolysaccharide. The relatively low number of clinical strains belonging to
      serogroup O36 did not correspond to the presence of anti-P. mirabilis O36
      antibodies in the blood donors' sera. Twenty-five percent of tested sera
      contained a statistically significant elevated level of antibodies reacting with
      thermostable surface antigens of P. mirabilis O36. The presence and amount of
      antibodies correlated with Thr399Ile TLR4 polymorphism types (P=0.044).

PMID- 18625012
TI  - A comparison of three molecular typing methods for the discrimination of
      Salmonella enterica serovar Infantis.
AB  - Seventy-six epidemiologically unrelated Salmonella enterica serovar Infantis (S.
      Infantis) isolates were typed by pulsed-field gel electrophoresis (PFGE),
      multiple amplification of phage loci typing (MAPLT) and multiple-locus variable
      number tandem-repeat analysis (MLVA). PFGE, using the restriction endonuclease
      XbaI, generated 23 different profiles for the 76 isolates (DI=0.848). MAPLT was
      undertaken using a combination of 11 primer sets based on bacteriophage sequences
      and generated 28 different profiles (DI=0.938). By contrast, MLVA only produced
      nine profiles (DI=0.668) with 13 different primer sets, including the five primer
      sets routinely used for S. Typhimurium typing. Reducing the number of MAPLT
      primer sets to four still provided a diversity index of 0.838. All three typing
      methods revealed two distinct lineages of S. Infantis, with most isolates
      demonstrating genetic traits of either lineage but not both. The results
      demonstrate that MAPLT can potentially provide greater discrimination and
      separation of S. Infantis isolates than both PFGE and MLVA. Furthermore, MAPLT
      data can be generated much more rapidly and with reduced labour input than PFGE
      and without the need for expensive PFGE electrophoresis equipment, nor does it
      require capillary sequencing of PCR fragments to accurately determine PCR
      fragment lengths as is the case with MLVA.

PMID- 18625014
TI  - The capacity of bovine endothelial cells to eliminate intracellular
      Staphylococcus aureus and Staphylococcus epidermidis is increased by the
      proinflammatory cytokines TNF-alpha and IL-1beta.
AB  - Staphylococcus aureus is a pathogenic bacterium causing clinical and subclinical
      bovine mastitis. Infections of the udder by S. aureus are frequently associated
      with the presence of Staphylococcus epidermidis, an opportunistic pathogen. We
      reported previously that the capacity of bovine endothelial cells (BEC) to
      endocytize S. aureus is associated with the activation of NF-kappaB and modulated
      by the proinflammatory cytokines TNF-alpha and IL-1beta. In this work, we explore
      the ability of BEC to eliminate intracellular S. aureus and S. epidermidis and
      their response to these cytokines. Time-kinetics survival experiments indicated
      that BEC eliminate intracellular S. epidermidis more efficiently. Replication of
      S. aureus, but not S. epidermidis, inside BEC was evident by an increase in
      intracellular bacteria recovered at 2 h postinfection. Afterwards, the
      intracellular number of staphylococci decreased gradually, reaching the lowest
      value at 24 h. Treatment of BEC with TNF-alpha or IL-1beta potentiated the
      capacity of BEC to eliminate both Staphylococcus species at the times tested.
      These results indicate that activation of the intrinsic antistaphylococcal
      response in BEC, enhanced by TNF-alpha and IL-1beta, is effective to eliminate S.
      aureus and S. epidermidis and suggest that endothelial cells may play a prominent
      role in the defense against infections caused by these bacteria.

PMID- 18625013
TI  - Helicobacter pylori and mitogen-activated protein kinases mediate activator
      protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in
      gastric epithelial cells.
AB  - Emerging evidence has suggested a critical role for activator protein-1 (AP)-1 in
      regulating various cellular functions. The goal of this study was to investigate
      the effects of Helicobacter pylori and mitogen-activated protein kinases (MAPK)
      on AP-1 subcomponents expression and AP-1 DNA-binding activity in gastric
      epithelial cells. We found that H. pylori infection resulted in a time- and dose
      dependent increase in the expression of the proteins c-Jun, JunB, JunD, Fra-1,
      and c-Fos, which make up the major AP-1 DNA-binding proteins in AGS and MKN45
      cells, while the expression levels of Fra-2 and FosB remained unchanged.
      Helicobacter pylori infection and MAPK inhibition altered AP-1 subcomponent
      protein expression and AP-1 DNA-binding activity, but did not change the overall
      subcomponent composition. Different clinical isolates of H. pylori showed various
      abilities to induce AP-1 DNA binding. Mutation of cagA, cagPAI, or vacA, and the
      nonphosphorylateable CagA mutant (cagA(EPISA)) resulted in less H. pylori-induced
      AP-1 DNA-binding activity, while mutation of the H. pylori flagella had no
      effect. extracellular signal-related kinase (ERK), p38, and c-Jun N-terminal
      kinase (JNK) each selectively regulated AP-1 subcomponent expression and DNA
      binding activity. These results provide more insight into how H. pylori and MAPK
      modulate AP-1 subcomponents in gastric epithelial cells to alter the expression
      of downstream target genes and affect cellular functions.

PMID- 18625015
TI  - Global gene expression patterns and induction of innate immune response in human
      laryngeal epithelial cells in response to Acinetobacter baumannii outer membrane
      protein A.
AB  - The outer membrane protein A of Acinetobacter baumannii (AbOmpA) is an important
      pathogen-associated molecular pattern that induces host cell death. We determined
      the gene expression profiles of human laryngeal epithelial HEp-2 cells in
      response to the sublethal concentration of recombinant AbOmpA (rAbOmpA) and
      investigated the molecular mechanisms by which rAbOmpA induces an innate immune
      response. The microarray analysis showed that rAbOmpA sequentially regulated a
      relatively small set of genes, including those associated with signal
      transductions and molecules involved in immune response. Among the differentially
      expressed genes involved in innate immune responses, the surface expression of
      Toll-like receptor 2 and the production of inducible nitric oxide synthase (iNOS)
      were prominently observed. However, rAbOmpA did not induce the production of
      proinflammatory cytokines and chemokines. rAbOmpA activated c-Jun N-terminal
      kinase (JNK) and extracellular signal-regulated kinase mitogen-activated protein
      kinases (MAPKs). Inhibition of JNK MAPK suppressed iNOS production in the rAbOmpA
      treated HEp-2 cells. These results suggest that interaction of laryngeal
      epithelial cells with AbOmpA has a significant impact on the induction of innate
      immunity during the early stages of A. baumannii infection.

PMID- 18625016
TI  - Differentiated S100A7 expression in infected tonsils and tonsils from allergic
      individuals.
AB  - Palatine tonsils are continuously exposed to microorganisms and antigens and
      secrete antimicrobial peptides as a first line of defense. S100A7 is a protein
      with antimicrobial and chemotactic properties. Our aim was to investigate how the
      expression of S100A7 in human palatine tonsils is affected by inflammatory
      processes. Tonsils obtained from 109 patients undergoing tonsillectomy were
      divided into groups of infected and noninfected as well as allergic and
      nonallergic, based on the results from tonsillar core culture tests and Phadiatop
      analysis, respectively. Western blot and immunohistochemistry were used to assess
      protein expression and real-time PCR was used to quantify mRNA levels. To explore
      the induction of S100A7, tonsils were stimulated with lipopolysaccharide in
      vitro. The immunohistochemical staining for S100A7 was most intense in the
      tonsillar epithelium, but the protein was also detected in B- and T-cell regions,
      which was confirmed with Western blot on isolated B and T cells. The S100A7
      expression appeared to be the highest in CD8+ T cells. Reduced mRNA levels of
      S100A7 were detected in infected tonsils as well as in tonsils from allergic
      individuals. In vitro stimulation of tonsils with lipopolysaccharide did not have
      any effect on the expression. The results suggest a role for S100A7 in recurrent
      tonsillitis and allergic disease.

PMID- 18625017
TI  - Comparison of mucosal B- and T-cell responses in Helicobacter pylori-infected
      subjects in a developing and a developed country.
AB  - Helicobacter pylori is highly endemic in developing countries, but comparatively
      little is known about mucosal immune responses to H. pylori in these settings.
      Therefore, we have compared B- and T-cell responses, with a focus on the
      gastrointestinal mucosa, in H. pylori-infected adults in a developing
      (Bangladesh) and a developed (Sweden) country. We found comparable numbers of
      CD19(+) B cells and CD4 (+)T cells and similar levels of H. pylori-specific IgA
      antibodies in gastric mucosa from Bangladeshi and Swedish volunteers. However,
      about threefold higher numbers of CD19(+) B cells and 12-fold increased levels of
      H. pylori-specific IgA antibodies were found in the duodenum of Bangladeshi
      subjects. The gastric and duodenal immune responses in Bangladeshi asymptomatic
      carriers and duodenal ulcer patients were comparable. Bangladeshi subjects had
      about twofold lower titers of H. pylori-specific IgA and IgG antibodies in the
      circulation compared with Swedish volunteers. In conclusion, our findings suggest
      that Bangladeshi individuals have comparable gastric immune responses, but lower
      systemic antibody responses to H. pylori, compared with Swedish volunteers.
      Increased inflammation is present in the duodenum of Bangladeshi volunteers,
      maybe as a result of frequent exposure to enteric infections in these
      individuals.

PMID- 18625018
TI  - Immune responsiveness of a novel peptidoglycan conjugate prepared from surface
      Candida immunogens: mannan and CR3-related protein.
AB  - Candida albicans expresses a CR3-related protein (CR3-RP) antigenically,
      structurally and functionally related to human adhesion glycoprotein, also known
      as Mac-l, the iC3b receptor, or complement receptor type 3. The purpose of the
      present study was to analyze the immunogenic properties of a novel CR3-RP
      glycoconjugate in a rabbit model. Cell-mediated responses revealed
      immunoenhancement triggered by CR3-RP glycoconjugate with respect to expression
      of IL-2 receptor subunit CD25 on B-lymphocytes and inductive increase of the
      CD4(+)/CD8(+) ratio compared with unconjugated cell wall mannan (P<0.001). Active
      immunization with the CR3-RP glycoconjugate resulted in an effective IgM-IgG
      isotypic switch even after the second booster. Altogether, it could be assumed
      that the novel peptide glycoconjugate is a prospective antigenic candidate for
      further Candida vaccine design.

PMID- 18625019
TI  - Efficient expression of laccase gene from white-rot fungus Schizophyllum commune
      in a transgenic tobacco plant.
AB  - Ligninolytic enzymes produced by white-rot fungi are effective degraders of
      recalcitrant aromatic environmental pollutants. However, gene sequences of these
      enzymes are rich in CpG dinucleotides, which are particularly unfavorable to
      efficient expression in plants. In order to develop a phytoremediation technique
      with a ligninolytic enzyme-producing transgenic plant, laccase cDNA (scL) from
      white-rot fungus Schizophyllum commune was used as a model ligninolytic enzyme,
      and we attempted to obtain the efficient expression of scL in a transgenic
      tobacco plant by decreasing the CpG-dinucleotide motif content. We constructed a
      mutagenized scL sequence, scL12, decreasing the CpG-dinucleotide motif content by
      12%, and scL12 was introduced into the tobacco plant. Much higher laccase
      activity was detected in transgenic scL12 plants than in transgenic scL plants
      and wild-type plants. Using reverse transcriptase-PCR analysis, scL12 was
      translated in transgenic scL12 plants whereas mRNA of scL was not detected in the
      transgenic scL plants, and scL, which is the product of the scL12 gene, was
      produced in the transgenic scL12 plants using native-polyacrylamide gel
      electrophoresis analysis. Moreover, transgenic scL12 plants were able to remove
      trichlorophenol more effectively than transgenic scL plants and wild-type plants.
      These results suggest that decreasing CpG-dinucleotide motif content in fungal
      target genes is a useful method for efficient expression of these genes in
      transgenic plants.

PMID- 18625020
TI  - Biochemical characterization of isovaleryl-CoA dehydrogenase (LiuA) of
      Pseudomonas aeruginosa and the importance of liu genes fora functional catabolic
      pathway of methyl-branched compounds.
AB  - Growth of Pseudomonas aeruginosa on acyclic terpene alcohols (citronellol) and on
      other methyl-branched compounds such as leucine or isovalerate requires a
      functional leucine/isovalerate utilization (Liu) pathway. In this study, we
      investigated the liuABCDE gene cluster by insertion mutant analysis, heterologous
      expression of liuA in Escherichia coli and by biochemical characterization of
      purified LiuA protein. Mutants with insertion in any of the liu genes were unable
      to utilize acyclic terpenes or leucine/isovalerate and confirmed the importance
      of the liu genes for catabolism of methyl-branched compounds. An insertion mutant
      in liuA was complemented by a liuA copy in trans, indicating that possible polar
      downstream effects of the insertion are not essential for growth. LiuA purified
      from recombinant E. coli revealed acyl-CoA dehydrogenase activity with isovaleryl
      CoA (KM 2.3 microM) and butyryl-CoA as substrates. Other acyl-CoA compounds such
      as isobutyryl-CoA, 3-hydroxybutyryl-CoA, octanoyl-CoA, citronellyl-CoA or 5
      methyl-hex-4-enoyl-CoA were not utilized. Experimental evidence for expression
      and essential functions of other Liu proteins in metabolism of methyl-branched
      compounds is provided.

PMID- 18625021
TI  - Requirements for the phosphorylation of the Escherichia coli EIIANtr protein in
      vivo.
AB  - The nitrogen-related phosphotransferase system (Ntr-PTS) is a paralogous system
      working in parallel to the well-known carbohydrate:PTS. In a chain of
      phosphotransfer reactions, EINtr and NPr (PtsO) deliver phosphoryl groups to the
      EIIANtr (PtsN) protein. EIIANtr is implicated in important regulatory processes
      such as the sigmaE-dependent cell envelope stress response and regulation of K+
      uptake. Phosphorylation is believed to trigger the output of EIIANtr in these
      regulations. EIIANtr is encoded within the gene cluster ptsN-yhbJ-ptsO, which is
      highly conserved in Proteobacteria. In this study, we investigated the
      phosphorylation of the Escherichia coli EIIANtr protein in vivo by 32P-labeling.
      We show that EIIANtr is readily phosphorylated in wild-type cells. This
      phosphorylation occurs at a single site, the histidine 73 in EIIANtr. YhbJ and
      NPr are dispensable for this phosphorylation. A detailed analysis revealed that
      both the energy coupling phosphotransferases of the Ntr-PTS as well as the
      'sugar'-PTS contribute to the phosphorylation of EIIANtr, suggesting cross talk
      between both systems.

PMID- 18625022
TI  - Identification of genes preferentially expressed during microcycle conidiation of
      Metarhizium anisopliae using suppression subtractive hybridization.
AB  - Microcycle conidiation has been defined as the production of conidia directly by
      a spore without the intervention of hyphal growth. The molecular mechanisms
      underlying this process are still poorly understood. Suppression subtractive
      hybridization was used here to isolate the genes preferentially expressed during
      microcycle conidiation vs. in normal conidiation hypha of Metarhizium anisopliae
      CQMa102, a common fungal pathogen of locusts. A total of 1600 clones from the
      subtracted cDNA library were screened by cDNA array dot blotting and 221 unique
      expressed sequence tags were identified as being differentially expressed. These
      genes were found to be homologous genes involved in various cellular processes,
      including general metabolism, protein synthesis, energy, cell-cycle and DNA
      processing, cellular transport, transcription, signal transduction and stress
      response. Real-time reverse transcriptase PCR assay of six randomly selected
      genes revealed that they are all highly expressed during microcycle conidiation.

PMID- 18625023
TI  - Streptomyces lunalinharesii spores contain chitin on the outer sheath.
AB  - Chitin from Streptomyces lunalinharesii spores, detected on its outermost surface
      layer, was isolated and characterized by chemical and spectroscopic methods,
      transmission electron microscopy and flow cytometry analysis. Gold-chitinase- and
      gold-lectin (Lycopersicum esculentum agglutinin, LEA)-conjugated labels were used
      in microscopy experiments, whereas a fluorescence-lectin (LEA) conjugate was used
      in flow cytometry analysis. Chitin isolation consisted of several steps of hot
      alkali and nitrous acid treatment, and the final material was obtained in the
      colloidal form. The infrared and the 13C CP/MAS NMR spectra of Streptomyces sp.
      colloidal chitin and colloidal chitin obtained from commercial crab shell chitin
      were very similar. Incubation of the spores with gold-labeled lectin, or gold
      labeled recombinant chitinase, showed the presence of gold particles around the
      spore surface, indicating the specific binding of the lectin or the recombinant
      chitinase with the chitin present on the outermost surface. Flow cytometry
      analysis, using the fluorescence-lectin conjugate, confirmed these results.
      According to scanning electron microscopy, S. lunalinharesii presented spore
      surface ornamentation belonging to the spiny group. This is the first detailed
      characterization of chitin on the spore's outermost layer from a Streptomyces
      species.

PMID- 18625024
TI  - Poly(gamma-L-diaminobutanoic acid), a novel poly(amino acid), coproduced with
      poly(epsilon-L-lysine) by two strains of Streptomyces celluloflavus.
AB  - Two poly(epsilon-L-lysine) (epsilon-PL) producer strains of Streptomyces
      celluloflavus secreted a novel polymeric substance into their culture broths
      along with epsilon-PL. Three types of HPLC analysis plus one- and two-dimensional
      1H and 13C nuclear magnetic resonance experiments revealed that the secreted
      substance was poly(gamma-L-diaminobutanoic acid) (gamma-PAB), an L-alpha,gamma
      diaminobutanoic acid (L-DAB) homopolymer linking between y-amino and alpha
      carboxylic acid functional groups. The gamma-PABs from the two strains had an
      identical chemical structure, and the same number-average molecular weight of
      2100-2200. No copolymers composed of the two amino acids L-DAB and L-lysine were
      found in either of the broths from the producers. Both strains coproduced high
      levels of the two poly(amino acid)s in the presence of SO4(2-) at pH 4.0 and 4.5
      L min(-1) aeration in a 5-L jar fermentor. gamma-PAB exhibited strong inhibitory
      activities against various yeasts and weaker actions against bacteria than
      epsilon-PL. gamma-PAB may have various biological functions similar to epsilon
      PL, and the use of gamma-PAB along with epsilon-PL would be advantageous for
      technical applications in various fields.

PMID- 18625025
TI  - The oligoribonuclease gene in Streptomyces coelicolor is not transcriptionally or
      translationally coupled to adpA, a key bldA target.
AB  - Transcriptional analysis of the gene in Streptomyces coelicolor encoding
      oligoribonuclease indicates that it is not transcriptionally or translationally
      coupled to adpA, a key bldA target for morphological differentiation.
      Interestingly, construction and phenotypic analysis of an S. coelicolor
      oligoribonuclease null mutant revealed a conditional defect in morphological
      differentiation that is reminiscent of bldA and other known developmental
      mutants.

PMID- 18625026
TI  - Characterization of the Pho89 phosphate transporter by functional hyperexpression
      in Saccharomyces cerevisiae.
AB  - The Na(+)-coupled, high-affinity Pho89 plasma membrane phosphate transporter in
      Saccharomyces cerevisiae has so far been difficult to study because of its low
      activity and special properties. In this study, we have used a
      pho84Deltapho87Deltapho90Deltapho91Delta quadruple deletion strain of S.
      cerevisiae devoid of all transporter genes specific for inorganic phosphate,
      except for PHO89, to functionally characterize Pho89 under conditions where its
      expression is hyperstimulated. Under these conditions, the Pho89 protein is
      strongly upregulated and is the sole high-capacity phosphate transporter
      sustaining cellular acquisition of inorganic phosphate. Even if Pho89 is
      synthesized in cells grown at pH 4.5-8.0, the transporter is functionally active
      under alkaline conditions only, with a K(m) value reflecting high-affinity
      properties of the transporter and with a transport rate about 100-fold higher
      than that of the protein in a wild-type strain. Even under these hyperexpressive
      conditions, Pho89 is unable to sense and signal extracellular phosphate levels.
      In cells grown at pH 8.0, Pho89-mediated phosphate uptake at alkaline pH is
      cation-dependent with a strong activation by Na(+) ions and sensitivity to
      carbonyl cyanide m-chlorophenylhydrazone. The contribution of H(+)- and Na(+)
      coupled phosphate transport systems in wild-type cells grown at different pH
      values was quantified. The contribution of the Na(+)-coupled transport system to
      the total cellular phosphate uptake activity increases progressively with
      increasing pH.

PMID- 18625027
TI  - The MAP kinase-activated protein kinase Rck2p plays a role in rapamycin
      sensitivity in Saccharomyces cerevisiae and Candida albicans.
AB  - Rck2p is a Hog1p-MAP kinase-activated protein kinase and regulates osmotic and
      oxidative stresses in budding yeast. In this study, we have demonstrated in both
      Saccharomyces cerevisiae and, the most medically important human fungal pathogen,
      Candida albicans that deletion of RCK2 renders cells sensitive to rapamycin, the
      inhibitor of target of rapamycin protein kinase controlling cell growth. The
      kinase activity of Rck2p does not seem to be required for this rapamycin
      sensitivity function in both eukaryotic microorganisms. Interestingly, the HOG
      pathway is not directly involved in cell sensitivity to rapamycin in S.
      cerevisiae, whereas disruption of CaHOG1 renders cells sensitive to rapamycin in
      C. albicans. In addition, we have shown that CaRck2p and its kinase activity are
      required for cell growth in C. albicans.

PMID- 18625028
TI  - The response of the yeast Saccharomyces cerevisiae to sudden vs. gradual changes
      in environmental stress monitored by expression of the stress response protein
      Hsp12p.
AB  - The response of the yeast Saccharomyces cerevisiae to sudden vs. gradual changes
      in different environmental stress conditions during both respiratory growth and
      aerobic fermentative growth in the presence of excess glucose was investigated by
      monitoring the level and rate of expression of the stress response protein Hsp12p
      using the fluorescent fusion construct Hsp12p-Gfp2p. The initial expression level
      and the rate of Hsp12p synthesis was significantly greater under glucose-limited
      conditions in the chemostat (D<0.14 h(-1)) compared with when excess glucose was
      present in the auxostat. Decreasing the dilution rate and the glucose
      concentration further in the A-stat resulted in increased Hsp12p expression,
      which was more marked when a rapid rather than a gradual change was affected.
      Common stress factors such as NaCl, ethanol and elevated temperature caused
      stress responses in both D-stat and auxo-accelerostat culture. The magnitude of
      the stress response depended on the stress factor, cultivation conditions as well
      as the rate of change of the stress factor. The rate of Hsp12p synthesis
      increased due to all applied stresses, with the observed increase between 2 and
      20 times lower when the stress was applied gradually rather than rapidly. The
      results suggested that the Hsp12p expression rate is a good indicator of applied
      stress in S. cerevisiae.

PMID- 18625029
TI  - Digital scoring of haemophilic arthropathy using radiographs is feasible.
AB  - Radiographs are important tools to evaluate structural changes in many joint
      diseases. In the case of haemophilic arthropathy (HA), the Pettersson score is
      widely used. The rising of digital radiography enables evaluation of these
      changes in a more quantitative and detailed manner, potentially improving
      diagnosis and follow-up. The aim of this study was to evaluate whether digital
      image analysis in the case of HA is feasible, using a presently available method
      for radiographic changes in knee osteoarthritis (OA), knee image digital analysis
      (KIDA). Sixty-two knee radiographs were scored according to Pettersson and with
      KIDA, each by two independent observers. Inter-observer variation and
      correlations between the two scoring methods were determined. The inter-observer
      variation was smaller for KIDA than for Pettersson and for KIDA not significantly
      different from evaluation of OA joints. Good correlations were found for the two
      methods where comparison of parameters was appropriate. Importantly, for each of
      the parameters within one point in the ordinal Pettersson score, a large window
      still existed in the continuous KIDA grading. Digital analysis of radiographs to
      quantify joint damage in HA is feasible. The use of continuous variables, as used
      in a digital method such as KIDA has the advantage that it enables objective and
      much more sensitive detection of small changes than by use of an ordinal analogue
      method such as the Pettersson score. Based on the present results, it would be
      worthwhile to adapt the KIDA method for the specific characteristics of HA and to
      extend the method to elbow and ankle radiographs.

PMID- 18625030
TI  - Successful surgery in severe haemophilia--a two-stage replacement therapy in
      resource-poor countries.

PMID- 18625033
TI  - Polymorphisms in the selenoprotein S gene: lack of association with autoimmune
      inflammatory diseases.
AB  - BACKGROUND: Selenoprotein S (SelS) protects the functional integrity of the
      endoplasmic reticulum against the deleterious effects of metabolic stress.
      SEPS1/SelS polymorphisms have been involved in the increased release of pro
      inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha
      and IL-6 in macrophages. We aimed at investigating the role of the SEPS1 variants
      previously associated with higher plasma levels of these cytokines and of the
      SEPS1 haplotypes in the susceptibility to develop immune-mediated diseases
      characterized by an inflammatory component. RESULTS: Six polymorphisms
      distributed through the SEPS1 gene (rs11327127, rs28665122, rs4965814,
      rs12917258, rs4965373 and rs2101171) were genotyped in more than two thousand
      patients suffering from type 1 diabetes, rheumatoid arthritis or inflammatory
      bowel diseases and 550 healthy controls included in the case-control study.
      CONCLUSION: Lack of association of SEPS1 polymorphisms or haplotypes precludes a
      major role of this gene increasing predisposition to these inflammatory diseases.

PMID- 18625031
TI  - Laminar and cytoarchitectonic features of the cerebral cortex in the Risso's
      dolphin (Grampus griseus), striped dolphin (Stenella coeruleoalba), and
      bottlenose dolphin (Tursiops truncatus).
AB  - The present investigation carried out Nissl, Kluver-Barrera, and Golgi studies of
      the cerebral cortex in three distinct genera of oceanic dolphins (Risso's
      dolphin, striped dolphin and bottlenose dolphin) to identify and classify
      cortical laminar and cytoarchitectonic structures in four distinct functional
      areas, including primary motor (M1), primary sensory (S1), primary visual (V1),
      and primary auditory (A1) cortices. The laminar and cytoarchitectonic
      organization of each of these cortical areas was similar among the three dolphin
      species. M1 was visualized as five-layer structure that included the molecular
      layer (layer I), external granular layer (layer II), external pyramidal layer
      (layer III), internal pyramidal layer (layer V), and fusiform layer (layer VI).
      The internal granular layer was absent. The cetacean sensory-related cortical
      areas S1, V1, and A1 were also found to have a five-layer organization comprising
      layers I, II, III, V and VI. In particular, A1 was characterized by the broadest
      layer I, layer II and developed band of pyramidal neurons in layers III
      (sublayers IIIa, IIIb and IIIc) and V. The patch organization consisting of the
      layer IIIb-pyramidal neurons was detected in the S1 and V1, but not in A1. The
      laminar patterns of V1 and S1 were similar, but the cytoarchitectonic structures
      of the two areas were different. V1 was characterized by a broader layer II than
      that of S1, and also contained the specialized pyramidal and multipolar stellate
      neurons in layers III and V.

PMID- 18625034
TI  - The auditory cortex of the bat Phyllostomus discolor: Localization and
      organization of basic response properties.
AB  - BACKGROUND: The mammalian auditory cortex can be subdivided into various fields
      characterized by neurophysiological and neuroarchitectural properties and by
      connections with different nuclei of the thalamus. Besides the primary auditory
      cortex, echolocating bats have cortical fields for the processing of temporal and
      spectral features of the echolocation pulses. This paper reports on location,
      neuroarchitecture and basic functional organization of the auditory cortex of the
      microchiropteran bat Phyllostomus discolor (family: Phyllostomidae). RESULTS: The
      auditory cortical area of P. discolor is located at parieto-temporal portions of
      the neocortex. It covers a rostro-caudal range of about 4800 mum and a medio
      lateral distance of about 7000 mum on the flattened cortical surface. The
      auditory cortices of ten adult P. discolor were electrophysiologically mapped in
      detail. Responses of 849 units (single neurons and neuronal clusters up to three
      neurons) to pure tone stimulation were recorded extracellularly. Cortical units
      were characterized and classified depending on their response properties such as
      best frequency, auditory threshold, first spike latency, response duration, width
      and shape of the frequency response area and binaural interactions. Based on
      neurophysiological and neuroanatomical criteria, the auditory cortex of P.
      discolor could be subdivided into anterior and posterior ventral fields and
      anterior and posterior dorsal fields. The representation of response properties
      within the different auditory cortical fields was analyzed in detail. The two
      ventral fields were distinguished by their tonotopic organization with opposing
      frequency gradients. The dorsal cortical fields were not tonotopically organized
      but contained neurons that were responsive to high frequencies only. CONCLUSION:
      The auditory cortex of P. discolor resembles the auditory cortex of other
      phyllostomid bats in size and basic functional organization. The tonotopically
      organized posterior ventral field might represent the primary auditory cortex and
      the tonotopically organized anterior ventral field seems to be similar to the
      anterior auditory field of other mammals. As most energy of the echolocation
      pulse of P. discolor is contained in the high-frequency range, the non
      tonotopically organized high-frequency dorsal region seems to be particularly
      important for echolocation.

PMID- 18625035
TI  - Satisfaction of inpatients with acute coronary syndrome in Bulgaria.
AB  - BACKGROUND: Patient satisfaction constitutes an important indicator for the
      quality of care. During the last years, Bulgaria changed its socialist health
      care system to a market-driven system. Despite the fact that the improvement of
      health care quality and patient satisfaction were put on top of the list of goals
      for the health care reforms, no studies of patient satisfaction with inpatient
      care have been conducted so far.Since cardiovascular diseases are amongst the
      major causes of death in Bulgaria, and strenuous efforts have been made to
      improve the quality of medical care of patients with acute coronary syndrome
      (ACS) during the last years, patient satisfaction in this group can be seen as an
      important example of the Bulgarian reforms. This study therefore investigates
      patient satisfaction of inpatients with ACS. METHODS: We performed structured
      face-to-face interviews with all patients with ACS, residing in a representative
      Bulgarian region who were discharged from hospitals in this region between
      September 1st and December 31st, 2004. We surveyed their socio-demographic
      status, overall satisfaction, change in complaints, self-perceived health status,
      functional possibilities in activities of daily living, satisfaction with life
      and self-reported condition at admission. We used descriptive methods as well as
      t-tests, chi-square tests, and logit models for data analysis. RESULTS: Face-to
      face interviews were carried out in 394 cases, of which 53.6% were men and 46.4%
      were women. 24% of the patients were satisfied with inhospital treatment, 62%
      were satisfied to some extent, and 14% were unsatisfied. The overall satisfaction
      of patients with ACS was significantly associated (p < 0.05) with the type of
      hospital, the number of family members living together and the severity of the
      disease at admission. Patients treated in urban and middle-size rural hospitals,
      patients living together with three or more family members, and patients with
      more severe conditions at admission reported higher satisfaction scores.
      CONCLUSION: ACS patient satisfaction with inhospital treatment in Bulgaria shows
      much room for improvement. Information obtained from satisfaction studies could
      be used at decision-making and hospital-management levels for improving new
      strategies and structural changes in the Bulgarian health care system.

PMID- 18625037
TI  - Identification of new HIV-1 Gag-specific cytotoxic T lymphocyte responses in
      BALB/c mice.
AB  - BACKGROUND: As HIV-specific cytotoxic T cells play a key role during acute and
      chronic HIV-1 infection in humans, the ability of potential anti-HIV vaccines to
      elicit strong, broad T cell responses is likely to be crucial. The HIV-1 Gag
      antigen is widely considered a relevant antigen for the development of an anti
      HIV vaccine since it is one of the most conserved viral proteins and is also
      known to induce T cell responses. In the majority of studies reporting Gag
      specific cellular immune responses induced by Gag-based vaccines, only a small
      number of Gag T cell epitopes were tested in preclinical mouse models, thus
      giving an incomplete picture of the numerous possible cellular immune responses
      against this antigen. As is, this partial knowledge of epitope-specific T cell
      responses directed to Gag will unavoidably result in a limited preclinical
      evaluation of Gag-based vaccines. RESULTS: In this study we identified new Gag
      CD8+ T cell epitopes in BALB/c mice vaccinated with the HIV-1 Gag antigen alone
      or in combination with the HIV-1 Tat protein, which was recently shown to broaden
      T cell responses directed to Gag. Specifically, we found that CTL responses to
      Gag may be directed to nine different CTL epitopes, and four of these were mapped
      as minimal CTL epitopes. CONCLUSION: These newly identified CTL epitopes should
      be considered in the preclinical evaluation of T cell responses induced by Gag
      based vaccines in mice.

PMID- 18625036
TI  - Norepinephrine to increase blood pressure in endotoxaemic pigs is associated with
      improved hepatic mitochondrial respiration.
AB  - INTRODUCTION: Low blood pressure, inadequate tissue oxygen delivery and
      mitochondrial dysfunction have all been implicated in the development of sepsis
      induced organ failure. This study evaluated the effect on liver mitochondrial
      function of using norepinephrine to increase blood pressure in experimental
      sepsis. METHODS: Thirteen anaesthetized pigs received endotoxin (Escherichia coli
      lipopolysaccharide B0111:B4; 0.4 microg/kg per hour) and were subsequently
      randomly assigned to norepinephrine treatment or placebo for 10 hours.
      Norepinephrine dose was adjusted at 2-hour intervals to achieve 15 mmHg increases
      in mean arterial blood pressure up to 95 mmHg. Systemic (thermodilution) and
      hepatosplanchnic (ultrasound Doppler) blood flow were measured at each step. At
      the end of the experiment, hepatic mitochondrial oxygen consumption (high
      resolution respirometry) and citrate synthase activity (spectrophotometry) were
      assessed. RESULTS: Mean arterial pressure (mmHg) increased only in norepinephrine
      treated animals (from 73 [median; range 69 to 81] to 63 [60 to 68] in controls [P
      = 0.09] and from 83 [69 to 93] to 96 [86 to 108] in norepinephrine-treated
      animals [P = 0.019]). Cardiac index and systemic oxygen delivery (DO2) increased
      in both groups, but significantly more in the norepinephrine group (P < 0.03 for
      both). Cardiac index (ml/min per kg) increased from 99 (range: 72 to 112) to 117
      (110 to 232) in controls (P = 0.002), and from 107 (84 to 132) to 161 (147 to
      340) in norepinephrine-treated animals (P = 0.001). DO2 (ml/min per kg) increased
      from 13 (range: 11 to 15) to 16 (15 to 24) in controls (P = 0.028), and from 16
      (12 to 19) to 29 (25 to 52) in norepinephrine-treated animals (P = 0.018).
      Systemic oxygen consumption (systemic VO2) increased in both groups (P < 0.05),
      whereas hepatosplanchnic flows, DO2 and VO2 remained stable. The hepatic lactate
      extraction ratio decreased in both groups (P = 0.05). Liver mitochondria complex
      I-dependent and II-dependent respiratory control ratios were increased in the
      norepinephrine group (complex I: 3.5 [range: 2.1 to 5.7] in controls versus 5.8
      [4.8 to 6.4] in norepinephrine-treated animals [P = 0.015]; complex II: 3.1 [2.3
      to 3.8] in controls versus 3.7 [3.3 to 4.6] in norepinephrine-treated animals [P
      = 0.09]). No differences were observed in citrate synthase activity. CONCLUSION:
      Norepinephrine treatment during endotoxaemia does not increase hepatosplanchnic
      flow, oxygen delivery or consumption, and does not improve the hepatic lactate
      extraction ratio. However, norepinephrine increases the liver mitochondria
      complex I-dependent and II-dependent respiratory control ratios. This effect was
      probably mediated by a direct effect of norepinephrine on liver cells.

PMID- 18625038
TI  - How residents and interns utilise and perceive the personal digital assistant and
      UpToDate.
AB  - BACKGROUND: In this era of evidence-based medicine, doctors are increasingly
      using information technology to acquire medical knowledge. This study evaluates
      how residents and interns utilise and perceive the personal digital assistant
      (PDA) and the online resource UpToDate. METHODS: This is a questionnaire survey
      of all residents and interns in a tertiary teaching hospital. RESULTS: Out of 168
      doctors, 134 (79.8%) responded to the questionnaire. Only 54 doctors (40.3%)
      owned a PDA. Although these owners perceived that the PDA was most useful for
      providing drug information, followed by medical references, scheduling and
      medical calculators, the majority of them did not actually have medical software
      applications downloaded on their PDAs. The greatest concerns highlighted for the
      PDA were the fear of loss and breakage, and the preference for working with
      desktop computers and paper. Meanwhile, only 76 doctors (56.7%) used UpToDate,
      even though the hospital had an institutional subscription for it. Although 93.4%
      of these users would recommend UpToDate to a colleague, only 57.9% stated that
      the use of UpToDate had led to a change in their management of patients.
      CONCLUSION: Although UpToDate and various PDA software applications were deemed
      useful by some of the residents and interns in our study, both digital tools were
      under-utilised. More should be done to facilitate the use of medical software
      applications on PDAs, to promote awareness of tools for evidence-based medicine
      such as UpToDate, and to facilitate the application of evidence-based medicine in
      daily clinical practice.

PMID- 18625039
TI  - Outlining eicosanoid biosynthesis in the crustacean Daphnia.
AB  - BACKGROUND: Eicosanoids are biologically active, oxygenated metabolites of three
      C20 polyunsaturated fatty acids. They act as signalling molecules within the
      autocrine or paracrine system in both vertebrates and invertebrates mainly
      functioning as important mediators in reproduction, the immune system and ion
      transport. The biosynthesis of eicosanoids has been intensively studied in
      mammals and it is known that they are synthesised from the fatty acid,
      arachidonic acid, through either the cyclooxygenase (COX) pathway; the
      lipoxygenase (LOX) pathway; or the cytochrome P450 epoxygenase pathway. However,
      little is still known about the synthesis and structure of the pathway in
      invertebrates. RESULTS: Here, we show transcriptomic evidence from Daphnia magna
      (Crustacea: Branchiopoda) together with a bioinformatic analysis of the D. pulex
      genome providing insight on the role of eicosanoids in these crustaceans as well
      as outlining a putative pathway of eicosanoid biosynthesis. Daphnia appear only
      to have one copy of the gene encoding the key enzyme COX, and phylogenetic
      analysis reveals that the predicted protein sequence of Daphnia COX clusters with
      other invertebrates. There is no current evidence of an epoxygenase pathway in
      Daphnia; however, LOX products are most certainly synthesised in daphnids.
      CONCLUSION: We have outlined the structure of eicosanoid biosynthesis in Daphnia,
      a key genus in freshwater ecosystems. Improved knowledge of the function and
      synthesis of eicosanoids in Daphnia and other invertebrates could have important
      implications for several areas within ecology. This provisional overview of
      daphnid eicosanoid biosynthesis provides a guide on where to focus future
      research activities in this area.

PMID- 18625040
TI  - Role of retinoic receptors in lung carcinogenesis.
AB  - Several in vitro and in vivo studies have examined the positive and negative
      effects of retinoids (vitamin A analogs) in premalignant and malignant lesions.
      Retinoids have been used as chemopreventive and anticancer agents because of
      their pleiotropic regulator function in cell differentiation, growth,
      proliferation and apoptosis through interaction with two types of nuclear
      receptors: retinoic acid receptors and retinoid X receptors. Recent
      investigations have gradually elucidated the function of retinoids and their
      signaling pathways and may explain the failure of earlier chemopreventive
      studies. In this review we have compiled basic and recent knowledge regarding the
      role of retinoid receptors in lung carcinogenesis. Sensitive and appropriate
      biological tools are necessary for screening the risk population and monitoring
      the efficacy of chemoprevention. Investigation of retinoid receptors is important
      and may contribute to the establishment of new strategies in chemoprevention for
      high-risk patients and in the treatment of lung cancer.

PMID- 18625042
TI  - Frequency, stability and differentiation of self-reported school fear and truancy
      in a community sample.
AB  - BACKGROUND: Surprisingly little is known about the frequency, stability, and
      correlates of school fear and truancy based on self-reported data of adolescents.
      METHODS: Self-reported school fear and truancy were studied in a total of N = 834
      subjects of the community-based Zurich Adolescent Psychology and Psychopathology
      Study (ZAPPS) at two times with an average age of thirteen and sixteen years.
      Group definitions were based on two behavioural items of the Youth Self-Report
      (YSR). Comparisons included a control group without indicators of school fear or
      truancy. The three groups were compared across questionnaires measuring emotional
      and behavioural problems, life-events, self-related cognitions, perceived
      parental behaviour, and perceived school environment. RESULTS: The frequency of
      self-reported school fear decreased over time (6.9 vs. 3.6%) whereas there was an
      increase in truancy (5.0 vs. 18.4%). Subjects with school fear displayed a
      pattern of associated internalizing problems and truants were characterized by
      associated delinquent behaviour. Among other associated psychosocial features,
      the distress coming from the perceived school environment in students with school
      fear is most noteworthy. CONCLUSION: These findings from a community study show
      that school fear and truancy are frequent and display different developmental
      trajectories. Furthermore, previous results are corroborated which are based on
      smaller and selected clinical samples indicating that the two groups display
      distinct types of school-related behaviour.

PMID- 18625041
TI  - Risks associated with magnetic resonance imaging and cervical collar in comatose,
      blunt trauma patients with negative comprehensive cervical spine computed
      tomography and no apparent spinal deficit.
AB  - INTRODUCTION: In blunt trauma, comatose patients (Glasgow Coma Scale score 3 to
      8) with a negative comprehensive cervical spine (CS) computed tomography
      assessment and no apparent spinal deficit, CS clearance strategies (magnetic
      resonance imaging [MRI] and prolonged cervical collar use) are controversial.
      METHODS: We conducted a literature review to delineate risks for coma, CS
      instability, prolonged cervical collar use, and CS MRI. RESULTS: Based on our
      search of the literature, the numbers of functional survivor patients among those
      who had sustained blunt trauma were as follows: 350 per 1,000 comatose unstable
      patients (increased intracranial pressure [ICP], hypotension, hypoxia, or early
      ventilator-associated pneumonia); 150 per 1,000 comatose high-risk patients (age
      > 45 years or Glasgow Coma Scale score 3 to 5); and 600 per 1,000 comatose stable
      patients (not unstable or high risk). Risk probabilities for adverse events among
      unstable, high-risk, and stable patients were as follows: 2.5% for CS
      instability; 26.2% for increased intensive care unit complications with prolonged
      cervical collar use; 9.3% to 14.6% for secondary brain injury with MRI
      transportation; and 20.6% for aspiration during MRI scanning (supine position).
      Additional risk probabilities for adverse events among unstable patients were as
      follows: 35.8% for increased ICP with cervical collar; and 72.1% for increased
      ICP during MRI scan (supine position). CONCLUSION: Blunt trauma coma functional
      survivor (independent living) rates are alarming. When a comprehensive CS
      computed tomography evaluation is negative and there is no apparent spinal
      deficit, CS instability is unlikely (2.5%). Secondary brain injury from the
      cervical collar or MRI is more probable than CS instability and jeopardizes
      cerebral recovery. Brain injury severity, probability of CS instability, cervical
      collar risk, and MRI risk assessments are essential when deciding whether CS MRI
      is appropriate and for determining the timing of cervical collar removal.

PMID- 18625043
TI  - In vitro studies on the modification of low-dose hyper-radiosensitivity in
      prostate cancer cells by incubation with genistein and estradiol.
AB  - BACKGROUND: As the majority of prostate cancers (PC) express estrogen receptors,
      we evaluated the combination of radiation and estrogenic stimulation (estrogen
      and genistein) on the radiosensitivity of PC cells in vitro. METHODS: PC cells
      LNCaP (androgen-sensitive) and PC-3 (androgen-independent) were evaluated.
      Estrogen receptor (ER) expression was analyzed by means of immunostaining. Cells
      were incubated in FCS-free media with genistein 10 microM and estradiol 10 microM
      24 h before irradiation and up to 24 h after irradiation. Clonogenic survival,
      cell cycle changes, and expression of p21 were assessed. RESULTS: LNCaP expressed
      both ER-alpha and ER-beta, PC-3 did not. Incubation of LNCaP and PC-3 with
      genistein resulted in a significant reduction of clonogenic survival. Incubation
      with estradiol exhibited in low concentrations (0.01 microM) stimulatory effects,
      while higher concentrations did not influence survival. Both genistein 10 microM
      and estradiol 10 microM increased low-dose hyper-radiosensitivity [HRS] in LNCaP,
      while hormonal incubation abolished HRS in PC-3. In LNCaP cells hormonal
      stimulation inhibited p21 induction after irradiation with 4 Gy. In PC-3 cells,
      the proportion of cells in G2/M was increased after irradiation with 4 Gy.
      CONCLUSION: We found an increased HRS to low irradiation doses after incubation
      with estradiol or genistein in ER-alpha and ER-beta positive LNCaP cells. This is
      of high clinical interest, as this tumor model reflects a locally advanced,
      androgen dependent PC. In contrast, in ER-alpha and ER-beta negative PC-3 cells
      we observed an abolishing of the HRS to low irradiation doses by hormonal
      stimulation. The effects of both tested compounds on survival were ER and p53
      independent. Since genistein and estradiol effects in both cell lines were
      comparable, neither ER- nor p53-expression seemed to play a role in the linked
      signalling. Nevertheless both compounds targeted the same molecular switch. To
      identify the underlying molecular mechanisms, further studies are needed.

PMID- 18625044
TI  - Observations from behind the bar: changing patrons' behaviours in response to
      smoke-free legislation in Scotland.
AB  - BACKGROUND: "Smoke-Free" legislation prohibiting smoking in all enclosed public
      places was introduced in March 2006. This qualitative study presents insights
      from bar workers about their observations of the changing social bar environment,
      changing patrons' behaviours and challenges bar workers have faced in managing
      smoke-free legislation. METHODS: Twelve in-depth interviews were conducted
      between November 2006 and January 2007 with a purposively-selected sample of bar
      workers, identified from a larger quantitative study evaluating the impact of the
      legislation in Scotland [the Bar Workers' Health and Environmental Tobacco Smoke
      Exposure project (BHETSE)]. RESULTS: Bar workers all spoke of the improvements
      the legislation had brought to their working lives and the greater comfort it
      appeared to offer patrons. Bar workers reported that patrons were generally quick
      to accept and comply with the new law, and that families had become a greater
      feature of pub life since the legislation. However, they expressed concerns that
      older men seemed to have had most difficulty adjusting to the legislation and
      lack of knowledge about the best practices they should adopt in order to reduce
      the risks of unattended drinks being spiked and of anti-social behaviour
      associated with patrons moving outside to smoke. CONCLUSION: Smoke-free
      legislation is changing the social context of smoking in Scotland. Further
      research to assess the impact the legislation is having on older male smokers and
      on the incidence of drink spiking would be useful. More specifically, bar workers
      would benefit from guidance on how to manage issues arising from patrons moving
      outside to smoke.

PMID- 18625045
TI  - Unsaturated long-chain fatty acids induce the respiratory burst of human
      neutrophils and monocytes in whole blood.
AB  - BACKGROUND: It is increasingly recognized that infectious complications in
      patients treated with total parenteral nutrition (TPN) may be caused by altered
      immune responses. Neutrophils and monocytes are the first line of defence against
      bacterial and fungal infection through superoxide anion production during the
      respiratory burst. To characterize the impact of three different types of lipid
      solutions that are applied as part of TPN formulations, we investigated the
      unstimulated respiratory burst activation of neutrophils and monocytes in whole
      blood. METHODS: Whole blood samples were incubated with LCT (Intralipid(R)),
      LCT/MCT (Lipofundin(R)) and LCT-MUFA (ClinOleic(R)) in three concentrations
      (0.06, 0.3 and 0.6 mg ml-1) for time periods up to one hour. Hydrogen peroxide
      production during the respiratory burst of neutrophils and monocytes was measured
      by flow cytometry. RESULTS: LCT and LCT-MUFA induced a hydrogen peroxide
      production in neutrophils and monocytes without presence of a physiological
      stimulus in contrast to LCT/MCT. CONCLUSION: We concluded that parenteral
      nutrition containing unsaturated oleic (C18:1) and linoleic (C18:2) acid can
      induce respiratory burst of neutrophils and monocytes, resulting in an elevated
      risk of tissue damage by the uncontrolled production of reactive oxygen species.
      Contradictory observations reported in previous studies may in part be the result
      of different methods used to determine hydrogen peroxide production.

PMID- 18625046
TI  - Complex population genetic and demographic history of the Salangid, Neosalanx
      taihuensis, based on cytochrome b sequences.
AB  - BACKGROUND: The Salangid icefish Neosalanx taihuensis (Salangidae) is an
      economically important fish, which is endemic to China, restricted to large
      freshwater systems (e.g. lakes, large rivers and estuaries) and typically exhibit
      low vagility. The continuous distribution ranges from the temperate region of the
      Huai and Yellow River basins to the subtropical region of the Pearl River basin.
      This wide ranging distribution makes the species an ideal model for the study of
      palaeoclimatic effects on population genetic structure and phylogeography. Here,
      we aim to analyze population genetic differentiation within and between river
      basins and demographic history in order to understand how this species responded
      to severe climatic oscillations, decline of the sea levels during the Pleistocene
      ice ages and tectonic activity. RESULTS: We obtained the complete mtDNA
      cytochrome b sequences (1141 bp) of 354 individuals from 13 populations in the
      Pearl River, the Yangze River and the Huai River basin. Thirty-six haplotypes
      were detected. Haplotype frequency distributions were strongly skewed, with most
      haplotypes (n = 24) represented only in single samples each and thus restricted
      to a single population. The most common haplotype (H36) was found in 49.15% of
      all individuals. Analysis of molecular variance (AMOVA) revealed a random pattern
      in the distribution of genetic diversity, which is inconsistent with contemporary
      hydrological structure. Significant levels of genetic subdivision were detected
      among populations within basins rather than between the three basins. Demographic
      analysis revealed that the population size in the Pearl River basin has remained
      relatively constant whereas the populations in the Yangze River and the Huai
      River basins expanded about 221 and 190 kyr ago, respectively, with the majority
      of mutations occurring after the last glacial maximum (LGM). CONCLUSION: The
      observed complex genetic pattern of N. taihuensis is coherent with a scenario of
      multiple unrelated founding events by long-distance colonization and dispersal
      combined with contiguous population expansion and locally restricted gene flow.
      We also found that this species was likely severely impacted by past glaciations.
      More favourable climate and the formation of large suitable habitations together
      facilitated population expansion after the late Quaternary (especially the LGM).
      We proposed that all populations should be managed and conserved separately,
      especially for habitat protection.

PMID- 18625047
TI  - Community mental health in India: A rethink.
AB  - BACKGROUND: Community care of the chronic mentally ill has always been prevalent
      in India, largely due to family involvement and unavailability of institutions.
      In the 80s, a few mental health clinics became operational in some parts of the
      country. The Schizophrenia Research Foundation (SCARF), an NGO in Chennai had
      established a community clinic in 1989 in Thiruporur, which was functional till
      1999. During this period various programmes such as training of the primary
      health center staff, setting up a referral system, setting up of a Citizen's
      Group, and self-employment schemes were initiated. It was decided to begin a
      follow up in 2005 to determine the present status of the schemes as well as the
      current status of the patients registered at the clinic. This we believed would
      lead to pointers to help evolve future community based programmes. METHODS: One
      hundred and eighty five patients with chronic mental illness were followed up and
      their present treatment status determined using a modified version of the
      Psychiatric and Personal History Schedule (PPHS). The resources created earlier
      were assessed and qualitative information was gathered during interviews with
      patient and families and other stakeholders to identify the reasons behind the
      sustenance or failure of these initiatives. RESULTS: Of the 185 patients followed
      up, 15% had continued treatment, 35% had stopped treatment, 21% had died, 12% had
      wandered away from home and 17% were untraceable. Of the patients who had
      discontinued treatment 25% were asymptomatic while 75% were acutely psychotic.The
      referral service was used by only 15% of the patients and mental health services
      provided by the PHC stopped within a year. The Citizen's group was functional for
      only a year and apart from chicken rearing, all other self-employment schemes
      were discontinued within a period of 6 months to 3 years.There were multiple
      factors contributing to the failure, the primary reasons being the limited access
      and associated expenses entailed in seeking treatment, inadequate knowledge about
      the illness, lack of support from the family and community and continued
      dependence by the family on the service provider to provide solutions.
      CONCLUSION: Community based initiatives in the management of mental disorders
      however well intentioned will not be sustainable unless the family and the
      community are involved in the intervention program with support being provided
      regularly by mental health professionals.

PMID- 18625048
TI  - Expert opinion as 'validation' of risk assessment applied to calf welfare.
AB  - BACKGROUND: Recently, a Risk Assessment methodology was applied to animal welfare
      issues in a report of the European Food Safety Authority (EFSA) on intensively
      housed calves. METHODS: Because this is a new and potentially influential
      approach to derive conclusions on animal welfare issues, a so-called semantic
      modelling type 'validation' study was conducted by asking expert scientists, who
      had been involved or quoted in the report, to give welfare scores for housing
      systems and for welfare hazards. RESULTS: Kendall's coefficient of concordance
      among experts (n = 24) was highly significant (P < 0.001), but low (0.29 and 0.18
      for housing systems and hazards respectively). Overall correlations with EFSA
      scores were significant only for experts with a veterinary or mixed (veterinary
      and applied ethological) background. Significant differences in welfare scores
      were found between housing systems, between hazards, and between experts with
      different backgrounds. For example, veterinarians gave higher overall welfare
      scores for housing systems than ethologists did, probably reflecting a difference
      in their perception of animal welfare. Systems with the lowest scores were veal
      calves kept individually in so-called "baby boxes" (veal crates) or in small
      groups, and feedlots. A suckler herd on pasture was rated as the best for calf
      welfare. The main hazards were related to underfeeding, inadequate colostrum
      intake, poor stockperson education, insufficient space, inadequate roughage, iron
      deficiency, inadequate ventilation, poor floor conditions and no bedding. Points
      for improvement of the Risk Assessment applied to animal welfare include linking
      information, reporting uncertainty and transparency about underlying values.
      CONCLUSION: The study provides novel information on expert opinion in relation to
      calf welfare and shows that Risk Assessment applied to animal welfare can benefit
      from a semantic modelling approach.

PMID- 18625049
TI  - Protective effects of a compound herbal extract (Tong Xin Luo) on free fatty acid
      induced endothelial injury: implications of antioxidant system.
AB  - BACKGROUND: Tong-Xin-Luo (TXL) - a mixture of herbal extracts, has been used in
      Chinese medicine with established therapeutic efficacy in patients with coronary
      artery disease. METHODS: We investigated the protective role of TXL extracts on
      endothelial cells injured by a known risk factor - palmitic acid (PA), which is
      elevated in metabolic syndrome and associated with cardiovascular complications.
      Human aortic endothelial cells (HAECs) were preconditioned with TXL extracts
      before exposed to PA for 24 hours. RESULTS: We found that PA (0.5 mM) exposure
      induced 73% apoptosis in endothelial cells. However, when HAECs were
      preconditioned with ethanol extracted TXL (100 microg/ml), PA induced only 7% of
      the endothelial cells into apoptosis. Using antibody-based protein microarray, we
      found that TXL attenuated PA-induced activation of p38-MAPK stress pathway. To
      investigate the mechanisms involved in TXL's protective effects, we found that
      TXL reduced PA-induced intracellular oxidative stress. Through AMPK pathway, TXL
      restored the intracellular antioxidant system, which was depressed by the PA
      treatment, with an increased expression of thioredoxin and a decreased expression
      of the thioredoxin interacting protein. CONCLUSION: In summary, our study
      demonstrates that TXL protects endothelial cells from PA-induced injury. This
      protection is likely mediated by boosting intracellular antioxidant capacity
      through AMPK pathway, which may account for the therapeutic efficacy in TXL
      mediated cardiovascular protection.

PMID- 18625050
TI  - Autoantigenic nuclear proteins of a clinically atypical renal vasculitis.
AB  - BACKGROUND: Systemic vasculitides constitute a heterogeneous group of diseases of
      autoimmunological origin characterized by inflammation of blood vessels and
      antibodies that react against autoantigens in a process that ultimately affects
      blood vessel walls. An important number of these patients present kidney disease.
      An endeavour of this area of research is the identification of autoantigens
      involved in these diseases. Accordingly, we used serum from a patient suffering
      from a microscopic polyangiitis, P-ANCA positive, manifesting a clinically
      atypical renal necrotizing glomerulonephritis and interstitial nephropathy for
      the identification of autoantigens; we also determined the prevalence of
      corresponding autoantibodies in other vasculitides, diabetic microangiopathy and
      in general population. METHODS: The patient's serum was used as a probe for the
      immunoscreening method SEREX to screen a human brain cDNA expression library.
      RESULTS: Four positive clones were isolated and sequenced. Clones Jos002 code for
      protein HDAC5, Jos014 for TFC4, Jos107 for RTF1, and Jos313 for POLDIP3
      polymerase. The four proteins are of nuclear localization. None of them had been
      reported as autoantigen. Recombinant proteins were synthesised and checked as
      antigens by western blot with different sera from controls and patients affected
      with other vasculitides and diabetic microangiopathy as well. Only the serum from
      the patient origin of this study recognized all recombinant proteins. CONCLUSION:
      We identify four nuclear proteins, HDAC5, TFC4, RTF1 and POLDIP3 polymerase as
      new autoantigens that could be used as markers in the diagnosis of subfamilies in
      immune diseases, although we cannot determine the role of these proteins in the
      aetiopathogenic process.

PMID- 18625051
TI  - Gastrointestinal failure score in critically ill patients: a prospective
      observational study.
AB  - INTRODUCTION: There are no universally accepted diagnostic criteria for
      gastrointestinal failure in critically ill patients. In the present study we
      tested whether the occurrence of food intolerance (FI) and intra-abdominal
      hypertension (IAH), combined in a 5-grade scoring system for assessment of
      gastrointestinal function (the Gastrointestinal Failure [GIF] score), predicts
      mortality. The prognostic value of the GIF score alone and in combination with
      the Sequential Organ Failure Assessment (SOFA) score is evaluated, and the
      incidence and outcome of gastrointestinal failure is described relative to the
      GIF score. METHODS: A total of 264 subsequently hospitalized patients, who were
      mechanically ventilated on admission and stayed in the intensive care unit (ICU)
      for longer than 24 hours, were prospectively studied. GIF score was documented
      daily as follows: 0 = normal gastrointestinal function; 1 = enteral feeding with
      under 50% of calculated needs or no feeding 3 days after abdominal surgery; 2 =
      FI or IAH; 3 = FI and IAH; and 4 = abdominal compartment syndrome (ACS).
      Admission parameters and mean GIF and SOFA scores for the first 3 days were used
      to predict ICU outcome. RESULTS: FI developed in 58.3%, IAH in 27.3%, and both
      together in 22.7% of patients. The mean GIF score for the first 3 days in the ICU
      was identified as an independent risk factor for mortality (odds ratio = 3.02,
      95% confidence interval = 1.63 to 5.59; P < 0.001). The GIF score integrated into
      the SOFA score allowed better prediction of ICU mortality than did the SOFA score
      alone, and was an independent predictor of mortality (odds ratio = 1.49, 95%
      confidence interval = 1.28 to 1.74; P < 0.001). The development of
      gastrointestinal failure (FI plus IAH) was associated with significantly higher
      ICU and 90-day mortality. CONCLUSION: The GIF score is useful for classifying
      information on the gastrointestinal system. The mean GIF score during the first 3
      days in the ICU had high prognostic value for ICU mortality. Development of
      gastrointestinal failure is associated with significantly impaired outcome.

PMID- 18625052
TI  - Do estimates of cost-utility based on the EQ-5D differ from those based on the
      mapping of utility scores?
AB  - BACKGROUND: Mapping has been used to convert scores from condition-specific
      measures into utility scores, and to produce estimates of cost-effectiveness. We
      sought to compare the QALY gains, and incremental cost per QALY estimates,
      predicted on the basis of mapping to those based on actual EQ-5D scores. METHODS:
      In order to compare 4 different interventions 389 individuals were asked to
      complete both the EQ-5D and the Western Ontartio and McMaster Universities
      Osteoarthritis Index (WOMAC) at baseline, 6, 12, and 24 months post-intervention.
      Using baseline data various mapping models were developed, where WOMAC scores
      were used to predict the EQ-5D scores. The performance of these models was tested
      by predicting the EQ-5D post-intervention scores. The preferred model (that with
      the lowest mean absolute error (MAE)) was used to predict the EQ-5D scores, at
      all time points, for individuals who had complete WOMAC and EQ-5D data. The mean
      QALY gain associated with each intervention was calculated, using both actual and
      predicted EQ-5D scores. These QALY gains, along with previously estimated changes
      in cost, were also used to estimate the actual and predicted incremental cost per
      QALY associated with each of the four interventions. RESULTS: The EQ-5D and the
      WOMAC were completed at baseline by 348 individuals, and at all time points by
      259 individuals. The MAE in the preferred model was 0.129, and the mean QALY
      gains for each of the four interventions was predicted to be 0.006, 0.058, 0.058,
      and 0.136 respectively, compared to the actual mean QALY gains of 0.087, 0.081,
      0.120, and 0.149. The most effective intervention was estimated to be associated
      with an incremental cost per QALY of pound6,068, according to our preferred
      model, compared to pound13,154 when actual data was used. CONCLUSION: We found
      that actual QALY gains, and incremental cost per QALY estimates, differed from
      those predicted on the basis of mapping. This suggests that though mapping may be
      of value in predicting the cost-effectiveness of interventions which have not
      been evaluated using a utility measure, future studies should be encouraged to
      include a method of actual utility measurement. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN93206785.

PMID- 18625053
TI  - The role of cumulative physical work load in symptomatic knee osteoarthritis - a
      case-control study in Germany.
AB  - OBJECTIVES: To examine the dose-response relationship between cumulative exposure
      to kneeling and squatting as well as to lifting and carrying of loads and
      symptomatic knee osteoarthritis (OA) in a population-based case-control study.
      METHODS: In five orthopedic clinics and five practices we recruited 295 male
      patients aged 25 to 70 with radiographically confirmed knee osteoarthritis
      associated with chronic complaints. A total of 327 male control subjects were
      recruited. Data were gathered in a structured personal interview. To calculate
      cumulative exposure, the self-reported duration of kneeling and squatting as well
      as the duration of lifting and carrying of loads were summed up over the entire
      working life. RESULTS: The results of our study support a dose-response
      relationship between kneeling/squatting and symptomatic knee osteoarthritis. For
      a cumulative exposure to kneeling and squatting > 10.800 hours, the risk of
      having radiographically confirmed knee osteoarthritis as measured by the odds
      ratio (adjusted for age, region, weight, jogging/athletics, and lifting or
      carrying of loads) is 2.4 (95% CI 1.1-5.0) compared to unexposed subjects.
      Lifting and carrying of loads is significantly associated with knee
      osteoarthritis independent of kneeling or similar activities. CONCLUSION: As the
      knee osteoarthritis risk is strongly elevated in occupations that involve both
      kneeling/squatting and heavy lifting/carrying, preventive efforts should
      particularly focus on these "high-risk occupations".

PMID- 18625054
TI  - Multiway modeling and analysis in stem cell systems biology.
AB  - BACKGROUND: Systems biology refers to multidisciplinary approaches designed to
      uncover emergent properties of biological systems. Stem cells are an attractive
      target for this analysis, due to their broad therapeutic potential. A central
      theme of systems biology is the use of computational modeling to reconstruct
      complex systems from a wealth of reductionist, molecular data (e.g., gene/protein
      expression, signal transduction activity, metabolic activity, etc.). A number of
      deterministic, probabilistic, and statistical learning models are used to
      understand sophisticated cellular behaviors such as protein expression during
      cellular differentiation and the activity of signaling networks. However, many of
      these models are bimodal i.e., they only consider row-column relationships. In
      contrast, multiway modeling techniques (also known as tensor models) can analyze
      multimodal data, which capture much more information about complex behaviors such
      as cell differentiation. In particular, tensors can be very powerful tools for
      modeling the dynamic activity of biological networks over time. Here, we review
      the application of systems biology to stem cells and illustrate application of
      tensor analysis to model collagen-induced osteogenic differentiation of human
      mesenchymal stem cells. RESULTS: We applied Tucker1, Tucker3, and Parallel Factor
      Analysis (PARAFAC) models to identify protein/gene expression patterns during
      extracellular matrix-induced osteogenic differentiation of human mesenchymal stem
      cells. In one case, we organized our data into a tensor of type protein/gene
      locus link x gene ontology category x osteogenic stimulant, and found that our
      cells expressed two distinct, stimulus-dependent sets of functionally related
      genes as they underwent osteogenic differentiation. In a second case, we
      organized DNA microarray data in a three-way tensor of gene IDs x osteogenic
      stimulus x replicates, and found that application of tensile strain to a collagen
      I substrate accelerated the osteogenic differentiation induced by a static
      collagen I substrate. CONCLUSION: Our results suggest gene- and protein-level
      models whereby stem cells undergo transdifferentiation to osteoblasts, and lay
      the foundation for mechanistic, hypothesis-driven studies. Our analysis methods
      are applicable to a wide range of stem cell differentiation models.

PMID- 18625055
TI  - Lack of association or interactions between the IL-4, IL-4Ralpha and IL-13 genes,
      and rheumatoid arthritis.
AB  - INTRODUCTION: A feature of rheumatoid arthritis (RA) is an imbalance between
      proinflammatory and anti-inflammatory cytokines. Several recent studies have
      implicated polymorphism in the IL-4 signalling pathway in the development of
      erosive RA. The aim of the present study was to investigate the role of
      polymorphism in the IL-4, IL-4Ralpha and IL-13 genes in RA, including an
      examination of epistasis. METHODS: A total of 965 Caucasian patients with RA
      (cases) and 988 healthy control individuals (controls) were genotyped for five
      variants in the IL-4/IL-13 gene cluster (5q31.1) and two functional variants IL
      4Ralpha (16p12.1). Individual genotype and haplotype frequencies were compared
      between cases and controls. The odd ratios were calculated with asymptotic 95%
      confidence intervals, and P values less than 0.05 were considered statistically
      significant. The potential association with radiological joint damage was also
      examined. Potential gene interactions were assessed using both stratified
      analysis and the linkage disequilibrium-based statistic. RESULTS: Genotype,
      allele and haplotype frequencies were equally distributed between RA cases and
      controls. Similarly, no association was detected between these variants and
      modified Larsen scores. Furthermore, no evidence of epistasis was detected
      between IL-4 or IL-13 genotypes and IL-4Ralpha. CONCLUSION: These results
      indicate that common variants of the IL-4/IL-13 pathway do not significantly
      contribute to RA susceptibility and radiological severity.

PMID- 18625056
TI  - Strained achilles tendon complicated by nocturnal dyspepsia probably caused by
      ibuprofen: a case report.
AB  - A 56-year-old male who is overweight experienced pain in his Achilles tendon
      after running four miles. He subsequently developed a severe limp. The condition
      was complicated by nocturnal dyspepsia probably caused by ibuprofen. His pain and
      limp were gone in six days.

PMID- 18625057
TI  - CpG oligodeoxynucleotide stimulates production of anti-neutrophil cytoplasmic
      antibodies in ANCA associated vasculitis.
AB  - BACKGROUND: Wegener's Granulomatosis and Microscopic Polyangiitis are life
      threatening systemic necrotizing vasculitides of unknown aetiology. The
      appearance of circulating antibodies to neutrophil cytoplasmic antigens (ANCA) is
      strongly associated with the development of the disease. A link between infection
      and disease has long been suspected, and the appearance of ANCA antibodies has
      been reported following bacterial and viral infections. The depletion of
      circulating B cells with monoclonal antibody therapy can induce remission, and
      this observation suggests a pathogenic role for B cells in this disease. As
      bacterial DNA is known to induce B cell proliferation and antibody production via
      TLR-9 stimulation, we have explored the possibility that unmethylated CpG
      oligodeoxynucleotide, as found in bacterial and viral DNA, may play a role in
      stimulating circulating autoreactive B cells to produce ANCA in patients with
      vasculitis. RESULTS: We have confirmed that unmethylated CpG oligonucleotide is a
      potent stimulator of antibody production by PBMC in vitro. The stimulation of
      PBMC with CpG oligonucleutides resulted in the production of similar amounts of
      IgG in both ANCA+ patients and normal controls. In spite of this, PR3 ANCA+
      patients synthesised significantly higher amount of IgG ANCA than normal
      controls. In MPO ANCA+ patients, there was a tendency for patients to produce
      higher amount of ANCA than controls, however, the difference did not reach
      significance. Furthermore, we were able to detect circulating MPO-reactive B
      cells by ELISpot assay from the peripheral blood of 2 MPO+ ANCA vasculitis
      patients. Together, this indicates that circulating anti-neutrophil autoreactive
      B cells are present in ANCA+ vasculitis patients, and they are capable of
      producing antibodies in response to CpG stimulation. Of note, CpG also induced
      the production of the relevant autoantibodies in patients with other types of
      autoimmune diseases. CONCLUSION: Circulating ANCA autoreactive B cells are
      present in patients with ANCA+ vasculitis. The production of ANCA from these
      cells in response to unmethylated CpG stimulation lead us to propose that
      stimulation of these cells by immunostimulatory DNA sequences such as CpG
      oligodeoxynucleotide during infection may provide a link between infection and
      ANCA associated vasculitis. This phenomenon may also apply to other antibody
      mediated autoimmune diseases.

PMID- 18625058
TI  - Evaluation of immunoglobulin purification methods and their impact on quality and
      yield of antigen-specific antibodies.
AB  - BACKGROUND: Antibodies are the main effectors against malaria blood-stage
      parasites. Evaluation of functional activities in immune sera from Phase 2a/b
      vaccine trials may provide invaluable information in the search for immune
      correlates of protection. However, the presence of anti-malarial-drugs, improper
      collection/storage conditions or concomitant immune responses against other
      pathogens can contribute to non-specific anti-parasite activities when the
      sera/plasma are tested in vitro. Purification of immunoglobulin is a standard
      approach for reducing such non-specific background activities, but the
      purification method itself can alter the quality and yield of recovered Ag
      specific antibodies. METHODS: To address this concern, various immunoglobulin
      (Ig) purification methods (protein G Sepharose, protein A/G Sepharose,
      polyethylene glycol and caprylic acid-ammonium sulphate precipitation) were
      evaluated for their impact on the quality, quantity and functional activity of
      purified rabbit and human Igs. The recovered Igs were analysed for yield and
      purity by SDS-PAGE, for quality by Ag-specific ELISAs (determining changes in
      titer, avidity and isotype distribution) and for functional activity by in vitro
      parasite growth inhibition assay (GIA). RESULTS: This comparison demonstrated
      that overall polyethylene glycol purification of human serum/plasma samples and
      protein G Sepharose purification of rabbit sera are optimal for recovering
      functional Ag-specific antibodies. CONCLUSION: Consequently, critical
      consideration of the purification method is required to avoid selecting non
      representative populations of recovered Ig, which could influence interpretations
      of vaccine efficacy, or affect the search for immune correlates of protection.

PMID- 18625059
TI  - Exploring consumer and pharmacist views on the professional role of the
      pharmacist with respect to natural health products: a study of focus groups.
AB  - BACKGROUND: Natural health products (NHPs) such as herbs, vitamins and
      homeopathic medicines, are currently available for sale in most Canadian
      pharmacies. However, most pharmacists report that they have limited knowledge
      about these products which have been regulated in Canada as a specific sub
      category of drugs. In this paper, consumers' and practicing pharmacists'
      perceptions of pharmacists' professional responsibilities with respect to NHPs
      are examined. METHODS: A total of 16 focus groups were conducted with consumers
      (n = 50) and pharmacists (n = 47) from four different cities across Canada
      (Vancouver, Edmonton, Toronto, and Halifax). RESULTS: In this paper, we
      illustrate the ways in which pharmacists' professional responsibilities are
      impacted by changing consumer needs. Many consumers in the study utilized a wide
      range of information resources that may or may not have included pharmacists.
      Nevertheless, the majority of consumers and pharmacists agreed that pharmacists
      should be knowledgeable about NHPs and felt that pharmacists should be able to
      manage drug-NHPs interactions as well as identify and evaluate the variety of
      information available to help consumers make informed decisions. CONCLUSION: This
      paper demonstrates that consumers' expectations and behaviour significantly
      impact pharmacists' perceptions of their professional responsibilities with
      respect to NHPs.

PMID- 18625060
TI  - A novel circular invasion assay mimics in vivo invasive behavior of cancer cell
      lines and distinguishes single-cell motility in vitro.
AB  - BACKGROUND: Classical in vitro wound-healing assays and other techniques designed
      to study cell migration and invasion have been used for many years to elucidate
      the various mechanisms associated with metastasis. However, many of these methods
      are limited in their ability to achieve reproducible, quantitative results that
      translate well in vivo. Such techniques are also commonly unable to elucidate
      single-cell motility mechanisms, an important factor to be considered when
      studying dissemination. Therefore, we developed and applied a novel in vitro
      circular invasion assay (CIA) in order to bridge the translational gap between in
      vitro and in vivo findings, and to distinguish between different modes of
      invasion. METHOD: Our method is a modified version of a standard circular wound
      healing assay with an added matrix barrier component (Matrigel), which better
      mimics those physiological conditions present in vivo. We examined 3 cancer cell
      lines (MCF-7, SCOV-3, and MDA-MB-231), each with a different established degree
      of aggressiveness, to test our assay's ability to detect diverse levels of
      invasiveness. Percent wound closure (or invasion) was measured using time-lapse
      microscopy and advanced image analysis techniques. We also applied the CIA
      technique to DLD-1 cells in the presence of lysophosphatidic acid (LPA), a
      bioactive lipid that was recently shown to stimulate cancer cell colony dispersal
      into single migratory cells, in order to validate our method's ability to detect
      collective and individual motility. RESULTS: CIA method was found to be highly
      reproducible, with negligible levels of variance measured. It successfully
      detected the anticipated low, moderate, and high levels of invasion that
      correspond to in vivo findings for cell lines tested. It also captured that DLD-1
      cells exhibit individual migration upon LPA stimulation, and collective behavior
      in its absence. CONCLUSION: Given its ability to both determine pseudo-realistic
      invasive cell behavior in vitro and capture subtle differences in cell motility,
      we propose that our CIA method may shed some light on the cellular mechanisms
      underlying cancer invasion and deserves inclusion in further studies. The broad
      implication of this work is the development of a reproducible, quantifiable, high
      resolution method that can be applied to various models, to include an unlimited
      number of parameters and/or agents that may influence invasion.

PMID- 18625061
TI  - The moderating role of parental smoking on their children's attitudes toward
      smoking among a predominantly minority sample: a cross-sectional analysis.
AB  - BACKGROUND: In general having a parent who smokes or smoked is a strong and
      consistent predictor of smoking initiation among their children while
      authoritative parenting style, open communication that demonstrates mutual
      respect between child and parent, and parental expectations not to smoke are
      protective. It has been hypothesized that parental smoking affects their
      children's smoking initiation through both imitation of the behavior and effects
      on attitudes toward smoking. The goals of the current analysis were to examine
      these two potential mechanisms. METHODS: In 2003, 1,417 high school students in
      Houston, Texas, completed a cross-sectional survey as part of the evaluation of
      an interactive smoking prevention and cessation program delivered via CD-ROM. To
      assess the relationship between number of parents who currently smoke and
      children's smoking status, we completed an unconditional logistic regression. To
      determine whether the attitudes that children of smokers hold toward smoking are
      significantly more positive than the attitudes of children of non-smokers we
      examined whether the parents smoking status moderated the relationship between
      children's attitudes toward smoking and their ever smoking using unconditional
      logistic regressions. RESULTS: Compared to participants whose parents did not
      currently smoke, participants who reported one or both parents currently smoke,
      had increased odds of ever smoking (OR = 1.31; 95% CI: 1.03-1.68; Wald chi2 =
      4.78 (df = 1) p = 0.03 and OR = 2.16; 95% CI: 1.51-3.10; Wald chi2 = 17.80 (df =
      1) p < 0.001, respectively). In addition, the relationship between attitudes and
      ever smoking was stronger among participants when at least one parent currently
      smokes (OR = 2.50; 95% CI: 1.96-3.19; Wald chi2 = 54.71 (df = 1) p < 0.001) than
      among participants whose parents did not smoke (OR = 1.72; 95% CI: 1.40-2.12;
      Wald chi2 = 26.45 (df = 1) p < 0.001). CONCLUSION: Children of smokers were more
      likely to smoke and reported more favorable attitudes toward smoking compared to
      children of non-smokers. One interpretation of our findings is that parental
      smoking not only directly influences behavior; it also moderates their children's
      attitudes towards smoking and thereby impacts their children's behavior. Our
      results demonstrate a continued need for primary prevention smoking interventions
      to be sensitive to the family context. They also underscore the importance of
      discussing parental smoking as a risk factor for smoking initiation, regardless
      of ethnicity, and of tailoring prevention messages to account for the influence
      that parental smoking status may have on the smoking attitudes and the associated
      normative beliefs.

PMID- 18625062
TI  - A periodic pattern generator for dental diversity.
AB  - BACKGROUND: Periodic patterning of iterative structures is a fundamental process
      during embryonic organization and development. Studies have shown how gene
      networks are employed to pattern butterfly eyespots, fly bristles and vertebrate
      epithelial appendages such as teeth, feathers, hair and mammary glands. Despite
      knowledge of how these features are organized, little is known about how
      diversity in periodic patterning is generated in nature. We address this problem
      through the molecular analysis of oral jaw dental diversity in Lake Malawi
      cichlids, where closely related species exhibit from 1 to 20 rows of teeth, with
      total teeth counts ranging from around 10 to 700. RESULTS: We investigate the
      expression of conserved gene networks (involving bmp2, bmp4, eda, edar, fgf8,
      pax9, pitx2, runx2, shh and wnt7b) known to pattern iterative structures and
      teeth in other vertebrates. We show that spatiotemporal variation in expression
      pattern reflects adult morphological diversity among three closely related Malawi
      cichlid species. Combinatorial epithelial expression of pitx2 and shh appears to
      govern the competence both of initial tooth sites and future tooth rows.
      Epithelial wnt7b and mesenchymal eda are expressed in the inter-germ and inter
      row regions, and likely regulate the spacing of these shh-positive units.
      Finally, we used chemical knockdown to demonstrate the fundamental role of
      hedgehog signalling and initial placode formation in the organization of the
      periodically patterned cichlid dental programme. CONCLUSION: Coordinated patterns
      of gene expression differ among Malawi species and prefigure the future-ordered
      distribution of functional teeth of specific size and spacing. This variation in
      gene expression among species occurs early in the developmental programme for
      dental patterning. These data show how a complex multi-rowed vertebrate dentition
      is organized and how developmental tinkering of conserved gene networks during
      iterative pattern formation can impact upon the evolution of trophic novelty.

PMID- 18625064
TI  - Chronic hypokalemia due to excessive cola consumption: a case report.
AB  - A 52-year-old man was noted to have severe chronic hypokalemia despite
      discontinuation of diuretic treatment for hypertension and aggressive oral
      potassium supplementation. His serum potassium normalized temporarily when he was
      hospitalized, but hypokalemia recurred after discharge. He complained of
      generalized weakness and fatigue, and occasional loose stools. Physical
      examination showed mild generalized muscle weakness. Laboratory testing ruled out
      renal potassium wasting. A dietary history revealed that he was consuming 4
      liters of cola per day, with a calculated fructose load of 396 grams per day.
      Since fructose absorption in the small bowel is relatively inefficient, this
      probably led to an osmotic diarrhea and GI potassium wasting. Physicians should
      ask their patients about soft drink consumption when they encounter unexplained
      hypokalemia.

PMID- 18625063
TI  - FGF15 promotes neurogenesis and opposes FGF8 function during neocortical
      development.
AB  - BACKGROUND: Growth, differentiation and regional specification of telencephalic
      domains, such as the cerebral cortex, are regulated by the interplay of secreted
      proteins produced by patterning centers and signal transduction systems deployed
      in the surrounding neuroepithelium. Among other signaling molecules, members of
      the fibroblast growth factor (FGF) family have a prominent role in regulating
      growth, differentiation and regional specification. In the mouse telencephalon
      the rostral patterning center expresses members of the Fgf family (Fgf8, Fgf15,
      Fgf17, Fgf18). FGF8 and FGF17 signaling have major roles in specification and
      morphogenesis of the rostroventral telencephalon, whereas the functions of FGF15
      and FGF18 in the rostral patterning center have not been established. RESULTS:
      Using Fgf15-/- mutant mice, we provide evidence that FGF15 suppresses
      proliferation, and that it promotes differentiation, expression of CoupTF1 and
      caudoventral fate; thus, reducing Fgf15 and Fgf8 dosage have opposite effects.
      Furthermore, we show that FGF15 and FGF8 differentially phosphorylate ERK
      (p42/44), AKT and S6 in cultures of embryonic cortex. Finally, we show that FGF15
      inhibits proliferation in cortical cultures. CONCLUSION: FGF15 and FGF8 have
      distinct signaling properties, and opposite effects on neocortical patterning and
      differentiation; FGF15 promotes CoupTF1 expression, represses proliferation and
      promotes neural differentiation.

PMID- 18625065
TI  - Prevalence of the prion protein gene E211K variant in U.S. cattle.
AB  - BACKGROUND: In 2006, an atypical U.S. case of bovine spongiform encephalopathy
      (BSE) was discovered in Alabama and later reported to be polymorphic for
      glutamate (E) and lysine (K) codons at position 211 in the bovine prion protein
      gene (Prnp) coding sequence. A bovine E211K mutation is important because it is
      analogous to the most common pathogenic mutation in humans (E200K) which causes
      hereditary Creutzfeldt - Jakob disease, an autosomal dominant form of prion
      disease. The present report describes a high-throughput matrix-associated laser
      desorption/ionization-time-of-flight mass spectrometry assay for scoring the Prnp
      E211K variant and its use to determine an upper limit for the K211 allele
      frequency in U.S. cattle. RESULTS: The K211 allele was not detected in 6062
      cattle, including those from five commercial beef processing plants (3892
      carcasses) and 2170 registered cattle from 42 breeds. Multiple nearby
      polymorphisms in Prnp coding sequence of 1456 diverse purebred cattle (42 breeds)
      did not interfere with scoring E211 or K211 alleles. Based on these results, the
      upper bounds for prevalence of the E211K variant was estimated to be extremely
      low, less than 1 in 2000 cattle (Bayesian analysis based on 95% quantile of the
      posterior distribution with a uniform prior). CONCLUSION: No groups or breeds of
      U.S. cattle are presently known to harbor the Prnp K211 allele. Because a carrier
      was not detected, the number of additional atypical BSE cases with K211 will also
      be vanishingly low.

PMID- 18625066
TI  - Identification of a set of genes showing regionally enriched expression in the
      mouse brain.
AB  - BACKGROUND: The Pleiades Promoter Project aims to improve gene therapy by
      designing human mini-promoters (< 4 kb) that drive gene expression in specific
      brain regions or cell-types of therapeutic interest. Our goal was to first
      identify genes displaying regionally enriched expression in the mouse brain so
      that promoters designed from orthologous human genes can then be tested to drive
      reporter expression in a similar pattern in the mouse brain. RESULTS: We have
      utilized LongSAGE to identify regionally enriched transcripts in the adult mouse
      brain. As supplemental strategies, we also performed a meta-analysis of published
      literature and inspected the Allen Brain Atlas in situ hybridization data. From a
      set of approximately 30,000 mouse genes, 237 were identified as showing specific
      or enriched expression in 30 target regions of the mouse brain. GO term over
      representation among these genes revealed co-involvement in various aspects of
      central nervous system development and physiology. CONCLUSION: Using a multi
      faceted expression validation approach, we have identified mouse genes whose
      human orthologs are good candidates for design of mini-promoters. These mouse
      genes represent molecular markers in several discrete brain regions/cell-types,
      which could potentially provide a mechanistic explanation of unique functions
      performed by each region. This set of markers may also serve as a resource for
      further studies of gene regulatory elements influencing brain expression.

PMID- 18625067
TI  - Surfactant replacement and open lung concept--comparison of two treatment
      strategies in an experimental model of neonatal ARDS.
AB  - BACKGROUND: Several concepts of treatment in neonatal ARDS have been proposed in
      the last years. The present study compared the effects of open lung concept
      positive pressure ventilation (PPVOLC) with a conventional ventilation strategy
      combined with administration of two different surfactant preparations on lung
      function and surfactant homoeostasis. METHODS: After repeated whole-lung saline
      lavage, 16 newborn piglets were assigned to either PPVOLC (n = 5) or surfactant
      treatment under conventional PPV using a natural bovine (n = 5) or a monomeric
      protein B based surfactant (n = 6). RESULTS: Comprehensive monitoring showed each
      treatment strategy to improve gas exchange and lung function, although the effect
      on PaO2 and pulmonary compliance declined over the study period in the surfactant
      groups. The overall improvement of the ventilation efficiency index (VEI) was
      significantly greater in the PPVOLC group. Phospholipid and protein analyses of
      the bronchoalveolar lavage fluid showed significant alterations to surfactant
      homoeostasis in the PPVOLC group, whereas IL-10 and SP-C mRNA expression was
      tendentially increased in the surfactant groups. CONCLUSION: The different
      treatment strategies applied could be shown to improve gas exchange and lung
      function in neonatal ARDS. To which extent differences in maintenance of lung
      function and surfactant homeostasis may lead to long-term consequences needs to
      be studied further.

PMID- 18625068
TI  - (Errors in statistical tests)3.
AB  - In 2004, Garcia-Berthou and Alcaraz published "Incongruence between test
      statistics and P values in medical papers," a critique of statistical errors that
      received a tremendous amount of attention. One of their observations was that the
      final reported digit of p-values in articles published in the journal Nature
      departed substantially from the uniform distribution that they suggested should
      be expected. In 2006, Jeng critiqued that critique, observing that the
      statistical analysis of those terminal digits had been based on comparing the
      actual distribution to a uniform continuous distribution, when digits obviously
      are discretely distributed. Jeng corrected the calculation and reported
      statistics that did not so clearly support the claim of a digit preference.
      However delightful it may be to read a critique of statistical errors in a
      critique of statistical errors, we nevertheless found several aspects of the
      whole exchange to be quite troubling, prompting our own meta-critique of the
      analysis.The previous discussion emphasized statistical significance testing. But
      there are various reasons to expect departure from the uniform distribution in
      terminal digits of p-values, so that simply rejecting the null hypothesis is not
      terribly informative. Much more importantly, Jeng found that the original p-value
      of 0.043 should have been 0.086, and suggested this represented an important
      difference because it was on the other side of 0.05. Among the most widely
      reiterated (though often ignored) tenets of modern quantitative research methods
      is that we should not treat statistical significance as a bright line test of
      whether we have observed a phenomenon. Moreover, it sends the wrong message about
      the role of statistics to suggest that a result should be dismissed because of
      limited statistical precision when it is so easy to gather more data.In response
      to these limitations, we gathered more data to improve the statistical precision,
      and analyzed the actual pattern of the departure from uniformity, not just its
      test statistics. We found variation in digit frequencies in the additional data
      and describe the distinctive pattern of these results. Furthermore, we found that
      the combined data diverge unambiguously from a uniform distribution. The
      explanation for this divergence seems unlikely to be that suggested by the
      previous authors: errors in calculations and transcription.

PMID- 18625069
TI  - Processing of predicted substrates of fungal Kex2 proteinases from Candida
      albicans, C. glabrata, Saccharomyces cerevisiae and Pichia pastoris.
AB  - BACKGROUND: Kexin-like proteinases are a subfamily of the subtilisin-like serine
      proteinases with multiple regulatory functions in eukaryotes. In the yeast
      Saccharomyces cerevisiae the Kex2 protein is biochemically well investigated,
      however, with the exception of a few well known proteins such as the alpha
      pheromone precursors, killer toxin precursors and aspartic proteinase
      propeptides, very few substrates are known. Fungal kex2 deletion mutants display
      pleiotropic phenotypes that are thought to result from the failure to
      proteolytically activate such substrates. RESULTS: In this study we have aimed at
      providing an improved assembly of Kex2 target proteins to explain the phenotypes
      observed in fungal kex2 deletion mutants by in vitro digestion of recombinant
      substrates from Candida albicans and C. glabrata. We identified CaEce1, CA0365,
      one member of the Pry protein family and CaOps4-homolog proteins as novel Kex2
      substrates. CONCLUSION: Statistical analysis of the cleavage sites revealed
      extended subsite recognition of negatively charged residues in the P1', P2' and
      P4' positions, which is also reflected in construction of the respective binding
      pockets in the ScKex2 enzyme. Additionally, we provide evidence for the existence
      of structural constrains in potential substrates prohibiting proteolysis.
      Furthermore, by using purified Kex2 proteinases from S. cerevisiae, P. pastoris,
      C. albicans and C. glabrata, we show that while the substrate specificity is
      generally conserved between organisms, the proteinases are still distinct from
      each other and are likely to have additional unique substrate recognition.

PMID- 18625070
TI  - Characteristics of evolving models of care for arthritis: a key informant study.
AB  - BACKGROUND: The burden of arthritis is increasing in the face of diminishing
      health human resources to deliver care. In response, innovative models of care
      delivery are developing to facilitate access to quality care. Most models have
      developed in response to local needs with limited evaluation. The primary
      objective of this study is to a) examine the range of models of care that deliver
      specialist services using a medical/surgical specialist and at least one other
      health care provider and b) document the strengths and challenges of the
      identified models. A secondary objective is to identify key elements of best
      practice models of care for arthritis. METHODS: Semi-structured interviews were
      conducted with a sample of key informants with expertise in arthritis from
      jurisdictions with primarily publicly-funded health care systems. Qualitative
      data were analyzed using a constant comparative approach to identify common types
      of models of care, strengths and challenges of models, and key components of
      arthritis care. RESULTS: Seventy-four key informants were interviewed from six
      countries. Five main types of models of care emerged. 1) Specialized arthritis
      programs deliver comprehensive, multidisciplinary team care for arthritis. Two
      models were identified using health care providers (e.g. nurses or
      physiotherapists) in expanded clinical roles: 2) triage of patients with
      musculoskeletal conditions to the appropriate services including specialists; and
      3) ongoing management in collaboration with a specialist. Two models promoting
      rural access were 4) rural consultation support and 5) telemedicine. Key
      informants described important components of models of care including
      knowledgeable health professionals and patients. CONCLUSION: A range of models of
      care for arthritis have been developed. This classification can be used as a
      framework for discussing care delivery. Areas for development include integration
      of care across the continuum, including primary care.

PMID- 18625071
TI  - An in silico analysis of T-box regulated genes and T-box evolution in
      prokaryotes, with emphasis on prediction of substrate specificity of
      transporters.
AB  - BACKGROUND: T-box anti-termination is an elegant and sensitive mechanism by which
      many bacteria maintain constant levels of amino acid-charged tRNAs. The amino
      acid specificity of the regulatory element is related to a so-called specifier
      codon and can in principle be used to guide the functional annotation of the
      genes controlled via the T-box anti-termination mechanism. RESULTS: Hidden Markov
      Models were defined to search the T-box regulatory element and were applied to
      all completed prokaryotic genomes. The vast majority of the genes found
      downstream of the retrieved elements encoded functionalities related to transport
      and synthesis of amino acids and the charging of tRNA. This is completely in line
      with findings reported in literature and with the proposed biological role of the
      regulatory element. For several species, the functional annotation of a large
      number of genes encoding proteins involved in amino acid transport could be
      improved significantly on basis of the amino acid specificity of the identified T
      boxes. In addition, these annotations could be extrapolated to a larger number of
      orthologous systems in other species. Analysis of T-box distribution confirmed
      that the element is restricted predominantly to species of the phylum Firmicutes.
      Furthermore, it appeared that the distribution was highly species specific and
      that in the case of amino acid transport some boxes seemed to "pop-up" only
      recently. CONCLUSION: We have demonstrated that the identification of the
      molecular specificity of a regulatory element can be of great help in solving
      notoriously difficult annotation issues, e.g. by defining the substrate
      specificity of genes encoding amino acid transporters on basis of the amino acid
      specificity of the regulatory T-box. Furthermore, our analysis of the species
      dependency of the occurrence of specific T-boxes indicated that these regulatory
      elements propagate in a semi-independent way from the genes that they control.

PMID- 18625072
TI  - The PPARgamma-selective ligand BRL-49653 differentially regulates the fate
      choices of rat calvaria versus rat bone marrow stromal cell populations.
AB  - BACKGROUND: Osteoblasts and adipocytes are derived from a common mesenchymal
      progenitor and an inverse relationship between expression of the two lineages is
      seen with certain experimental manipulations and in certain diseases, i.e.,
      osteoporosis, but the cellular pathway(s) and developmental stages underlying the
      inverse relationship is still under active investigation. To determine which
      precursor mesenchymal cell types can differentiate into adipocytes, we compared
      the effects of BRL-49653 (BRL), a selective ligand for peroxisome proliferators
      activated receptor (PPAR)gamma, a master transcription factor of adipogenesis, on
      osteo/adipogeneis in two different osteoblast culture models: the rat bone marrow
      (RBM) versus the fetal rat calvaria (RC) cell system. RESULTS: BRL increased the
      number of adipocytes and corresponding marker expression, such as lipoprotein
      lipase, fatty acid-binding protein (aP2), and adipsin, in both culture models,
      but affected osteoblastogenesis only in RBM cultures, where a reciprocal decrease
      in bone nodule formation and osteoblast markers, e.g., osteopontin, alkaline
      phosphatase (ALP), bone sialoprotein, and osteocalcin was seen, and not in RC
      cell cultures. Even though adipocytes were histologically undetectable in RC
      cultures not treated with BRL, RC cells expressed PPAR and CCAAT/enhancer binding
      protein (C/EBP) mRNAs throughout osteoblast development and their expression was
      increased by BRL. Some single cell-derived BRL-treated osteogenic RC colonies
      were stained not only with ALP/von Kossa but also with oil red O and co-expressed
      the mature adipocyte marker adipsin and the mature osteoblast marker OCN, as well
      as PPAR and C/EBP mRNAs. CONCLUSION: The data show that there are clear
      differences in the capacity of BRL to alter the fate choices of precursor cells
      in stromal (RBM) versus calvarial (RC) cell populations and that recruitment of
      adipocytes can occur from multiple precursor cell pools (committed preadipocyte
      pool, multi-/bipotential osteo-adipoprogenitor pool and conversion of
      osteoprogenitor cells or osteoblasts into adipocytes (transdifferentiation or
      plasticity)). They also show that mechanisms beyond activation of PPARgamma by
      its ligand are required for changing the fate of committed osteoprogenitor cells
      and/or osteoblasts into adipocytes.

PMID- 18625073
TI  - Clinical and biochemical effects of a combination botanical product (ClearGuard)
      for allergy: a pilot randomized double-blind placebo-controlled trial.
AB  - BACKGROUND: Botanical products are frequently used for treatment of nasal
      allergy. Three of these substances, Cinnamomum zeylanicum, Malpighia glabra, and
      Bidens pilosa, have been shown to have a number of anti-allergic properties in
      vitro. The current study was conducted to determine the effects of these combined
      ingredients upon the nasal response to allergen challenge in patients with
      seasonal allergic rhinitis. METHODS: Twenty subjects were randomized to receive
      the combination botanical product, (CBP) 2 tablets three times a day, loratadine,
      10 mg once a day in the morning, or placebo, using a randomized, double-blinded
      crossover design. Following 2 days of each treatment and during the third day of
      treatment, subjects underwent a nasal allergen challenge (NAC), in which nasal
      symptoms were assessed after each challenge dose and every 2 hours for 8 hours.
      Nasal lavage fluid was assessed for tryptase, prostaglandin D2, and leukotriene
      E4 concentrations and inflammatory cells. RESULTS: Loratadine significantly
      reduced the total nasal symptom score during the NAC compared with placebo (P =
      0.04) while the CBP did not. During the 8 hour period following NAC, loratadine
      and the CBP both reduced NSS compared with placebo (P = 0.034 and P = 0.029,
      respectively). Analysis of nasal lavage fluid demonstrated that the CBP prevented
      the increase in prostaglandin D2 release following NAC, while neither loratadine
      nor placebo had this effect. None of the treatments significantly affected
      tryptase or leukotriene E4 release or inflammatory cell infiltration. CONCLUSION:
      The CBP significantly reduced NSS during the 8 hours following NAC and marginally
      inhibited the release of prostaglandin D2 into nasal lavage fluid, suggesting
      potential clinical utility in patients with allergic rhinitis.

PMID- 18625074
TI  - Primary Biliary Cirrhosis with a normal Alkaline Phosphatase: a case report.
AB  - A 78 year-old lady presented with abdominal swelling and fatigue. She was
      anaemic with mild hypoalbuminaemia, and had a normal alkaline phosphatase.
      Computed tomography showed hepatosplenomegaly and mild ascites. Anti
      mitochondrial antibodies were strongly positive, as were anti nuclear antibodies,
      and the gamma glutamyl-transferase was shown to be elevated. A diagnosis of
      primary biliary cirrhosis was made. A brief discussion of treatment of primary
      biliary cirrhosis follows. The case is notable for the fact that primary biliary
      cirrhosis can manifest clinically without an elevation in alkaline phosphatase -
      normally the hallmark of the disease.

PMID- 18625076
TI  - Abdominal shotgun trauma: A case report.
AB  - INTRODUCTION: One of the most lethal mechanisms of injury is shotgun wound and
      particularly the abdominal one. CASE PRESENTATION: We report a case of a 45 years
      old male suffering abdominal shotgun trauma, who survived his injuries.
      CONCLUSION: The management of the abdominal shotgun wounds is mainly dependent on
      clinical examination and clinical judgment, while requires advanced surgical
      skills.

PMID- 18625075
TI  - Nicotinic acetylcholine receptor subunit variants are associated with blood
      pressure; findings in the Old Order Amish and replication in the Framingham Heart
      Study.
AB  - BACKGROUND: Systemic blood pressure, influenced by both genetic and environmental
      factors, is regulated via sympathetic nerve activity. We assessed the role of
      genetic variation in three subunits of the neuromuscular nicotinic acetylcholine
      receptor positioned on chromosome 2q, a region showing replicated evidence of
      linkage to blood pressure. METHODS: We sequenced CHRNA1, CHRND and CHRNG in 24
      Amish subjects from the Amish Family Diabetes Study (AFDS) and identified 20
      variants. We then performed association analysis of non-redundant variants (n =
      12) in the complete AFDS cohort of 1,189 individuals, and followed by genotyping
      blood pressure-associated variants (n = 5) in a replication sample of 1,759
      individuals from the Framingham Heart Study (FHS). RESULTS: The minor allele of a
      synonymous coding SNP, rs2099489 in CHRNG, was associated with higher systolic
      blood pressure in both the Amish (p = 0.0009) and FHS populations (p = 0.009)
      (minor allele frequency = 0.20 in both populations). CONCLUSION: CHRNG is
      currently thought to be expressed only during fetal development. These findings
      support the Barker hypothesis, that fetal genotype and intra-uterine environment
      influence susceptibility to chronic diseases later in life. Additional studies of
      this variant in other populations, as well as the effect of this variant on
      acetylcholine receptor expression and function, are needed to further elucidate
      its potential role in the regulation of blood pressure. This study suggests for
      the first time in humans, a possible role for genetic variation in the
      neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit,
      in systolic blood pressure regulation.

PMID- 18625077
TI  - Using supernetworks to distinguish hybridization from lineage-sorting.
AB  - BACKGROUND: A simple and widely used approach for detecting hybridization in
      phylogenies is to reconstruct gene trees from independent gene loci, and to look
      for gene tree incongruence. However, this approach may be confounded by factors
      such as poor taxon-sampling and/or incomplete lineage-sorting. RESULTS: Using
      coalescent simulations, we investigated the potential of supernetwork methods to
      differentiate between gene tree incongruence arising from taxon sampling and
      incomplete lineage-sorting as opposed to hybridization. For few hybridization
      events, a large number of independent loci, and well-sampled taxa across these
      loci, we found that it was possible to distinguish incomplete lineage-sorting
      from hybridization using the filtered Z-closure and Q-imputation supernetwork
      methods. Moreover, we found that the choice of supernetwork method was less
      important than the choice of filtering, and that count-based filtering was the
      most effective filtering technique. CONCLUSION: Filtered supernetworks provide a
      tool for detecting and identifying hybridization events in phylogenies, a tool
      that should become increasingly useful in light of current genome sequencing
      initiatives and the ease with which large numbers of independent gene loci can be
      determined using new generation sequencing technologies.

PMID- 18625078
TI  - Specific genetic markers for detecting subtypes of dengue virus serotype-2 in
      isolates from the states of Oaxaca and Veracruz, Mexico.
AB  - BACKGROUND: Dengue (DEN) is an infectious disease caused by the DEN virus (DENV),
      which belongs to the Flavivirus genus in the family Flaviviridae. It has a (+)
      sense RNA genome and is mainly transmitted to humans by the vector mosquito Aedes
      aegypti. Dengue fever (DF) and dengue hemorrhagic fever (DHF) are caused by one
      of four closely related virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4).
      Epidemiological and evolutionary studies have indicated that host and viral
      factors are involved in determining disease outcome and have proved the
      importance of viral genotype in causing severe epidemics. Host immune status and
      mosquito vectorial capacity are also important influences on the severity of
      infection. Therefore, an understanding of the relationship between virus variants
      with altered amino acids and high pathogenicity will provide more information on
      the molecular epidemiology of DEN. Accordingly, knowledge of the DENV serotypes
      and genotypes circulating in the latest DEN outbreaks around the world, including
      Mexico, will contribute to understanding DEN infections. RESULTS: 1. We obtained
      88 isolates of DENV, 27 from Oaxaca and 61 from Veracruz. 2. Of these 88
      isolates, 16 were serotype 1; 62 serotype 2; 7 serotype 3; and 2 serotype 4. One
      isolate had 2 serotypes (DENV-2 and -1). 3. Partial nucleotide sequences of the
      genes encoding C- prM (14 sequences), the NS3 helicase domain (7 sequences), the
      NS5 S-adenosyl methionine transferase domain (7 sequences) and the RNA-dependent
      RNA polymerase (RdRp) domain (18 sequences) were obtained. Phylogenetic analysis
      showed that DENV-2 isolates belonged to the Asian/American genotype. In addition,
      the Asian/American genotype was divided into two clusters, one containing the
      isolates from 2001 and the other the isolates from 2005-2006 with high bootstrap
      support of 94%. CONCLUSION: DENV-2 was the predominant serotype in the DF and DHF
      outbreak from 2005 to 2006 in Oaxaca State as well as in the 2006 outbreak in
      Veracruz State, with the Asian/American genotype prevalent in both states.
      Interestingly, DENV-1 and DENV-2 were the only serotypes related to DHF cases. In
      contrast, DENV-3 and DENV-4 were poorly represented according to epidemiological
      data reported in Mexico. We found that isoleucine was replaced by valine at
      residue 106 of protein C in the isolates from these 2005-2006 outbreaks and in
      those from the 1997, 1998 and 2001 outbreaks in the Caribbean islands. We
      suggested that this amino acid change may be used as a signature for isolates
      arising in the Caribbean islands and pertaining to the Asian/American genotype.
      Other amino acid changes are specific for the Asian/American, Asian and American
      strains.

PMID- 18625079
TI  - A dengue receptor as possible genetic marker of vector competence in Aedes
      aegypti.
AB  - BACKGROUND: Vector competence refers to the intrinsic permissiveness of an
      arthropod vector for infection, replication and transmission of a virus.
      Notwithstanding studies of Quantitative Trait Loci (QTL) that influence the
      ability of Aedes aegypti midgut (MG) to become infected with dengue virus (DENV),
      no study to date has been undertaken to identify genetic markers of vector
      competence. Furthermore, it is known that mosquito populations differ greatly in
      their susceptibility to flaviviruses. Differences in vector competence may, at
      least in part, be due to the presence of specific midgut epithelial receptors and
      their identification would be a significant step forward in understanding the
      interaction of the virus with the mosquito. The first interaction of DENV with
      the insect is through proteins in the apical membrane of the midgut epithelium
      resulting in binding and receptor-mediated endocytosis of the virus, and this
      determines cell permissiveness to infection. The susceptibility of mosquitoes to
      infection may therefore depend on their specific virus receptors. To study this
      interaction in Ae. aegypti strains that differ in their vector competence for
      DENV, we investigated the DS3 strain (susceptible to DENV), the IBO-11 strain
      (refractory to infection) and the membrane escape barrier strain, DMEB, which is
      infected exclusively in the midgut epithelial cells. RESULTS: (1) We determined
      the MG proteins that bind DENV by an overlay protein binding assay (VOPBA) in Ae.
      aegypti mosquitoes of the DS3, DMEB and IBO-11 strains. The main protein
      identified had an apparent molecular weight of 67 kDa, although the protein
      identified in the IBO-11 strain showed a lower mass (64 kDa). (2) The midgut
      proteins recognized by DENV were also determined by VOPBA after two-dimensional
      gel electrophoresis. (3) To determine whether the same proteins were identified
      in all three strains, we obtained polyclonal antibodies against R67 and R64 and
      tested them against the three strains by immunoblotting; both antibodies
      recognized the 67 and 64 kDa proteins, corroborating the VOPBA results. (4)
      Specific antibodies against both proteins were used for immunofluorescent
      location by confocal microscopy; the antibodies recognized the basal lamina all
      along the MG, and cell membranes and intercellular spaces from the middle to the
      end of the posterior midgut (pPMG) in the neighborhood of the hindgut. (5)
      Quantitative analysis showed more intense fluorescence in DS3 and DMEB than in
      IBO-11. (6) The viral envelope antigen was not homogeneously distributed during
      MG infection but correlated with MG density and the distribution of R67/R64.
      CONCLUSION: In this paper we provide evidence that the 67 kDa protein (R67/R64),
      described previously as a DENV receptor, is related to vector competence in Ae.
      aegypti. Consequently, our results strongly suggest that this protein may be a
      marker of vector competence for DENV in Ae. aegypti mosquitoes.

PMID- 18625080
TI  - Computational identification of ubiquitylation sites from protein sequences.
AB  - BACKGROUND: Ubiquitylation plays an important role in regulating protein
      functions. Recently, experimental methods were developed toward effective
      identification of ubiquitylation sites. To efficiently explore more undiscovered
      ubiquitylation sites, this study aims to develop an accurate sequence-based
      prediction method to identify promising ubiquitylation sites. RESULTS: We
      established an ubiquitylation dataset consisting of 157 ubiquitylation sites and
      3676 putative non-ubiquitylation sites extracted from 105 proteins in the UbiProt
      database. This study first evaluates promising sequence-based features and
      classifiers for the prediction of ubiquitylation sites by assessing three kinds
      of features (amino acid identity, evolutionary information, and physicochemical
      property) and three classifiers (support vector machine, k-nearest neighbor, and
      NaiveBayes). Results show that the set of used 531 physicochemical properties and
      support vector machine (SVM) are the best kind of features and classifier
      respectively that their combination has a prediction accuracy of 72.19% using
      leave-one-out cross-validation.Consequently, an informative physicochemical
      property mining algorithm (IPMA) is proposed to select an informative subset of
      531 physicochemical properties. A prediction system UbiPred was implemented by
      using an SVM with the feature set of 31 informative physicochemical properties
      selected by IPMA, which can improve the accuracy from 72.19% to 84.44%. To
      further analyze the informative physicochemical properties, a decision tree
      method C5.0 was used to acquire if-then rule-based knowledge of predicting
      ubiquitylation sites. UbiPred can screen promising ubiquitylation sites from
      putative non-ubiquitylation sites using prediction scores. By applying UbiPred,
      23 promising ubiquitylation sites were identified from an independent dataset of
      3424 putative non-ubiquitylation sites, which were also validated by using the
      obtained prediction rules. CONCLUSION: We have proposed an algorithm IPMA for
      mining informative physicochemical properties from protein sequences to build an
      SVM-based prediction system UbiPred. UbiPred can predict ubiquitylation sites
      accompanied with a prediction score each to help biologists in identifying
      promising sites for experimental verification. UbiPred has been implemented as a
      web server and is available at http://iclab.life.nctu.edu.tw/ubipred.

PMID- 18625082
TI  - Men's preferences for women's profile waist-to-hip ratio, breast size, and ethnic
      group in Britain and South Africa.
AB  - One particular aspect of the literature on preferences for female body shapes has
      focused on the purported universality of preferences for a low waist-to-hip ratio
      (WHR), despite substantial evidence of cross-cultural variability in such
      preferences. In the present study, we examined the effects of manipulating
      women's profile WHR, breast size, and ethnicity on men's ratings of physical
      attractiveness and health. A total of 51 African men in South Africa, 56 British
      Africans, and 114 British Caucasians rated 12 line drawings that varied in two
      levels of ethnicity, three levels of WHR, and two levels of breast size. Overall,
      the results suggested that there were cross-cultural differences in preferred
      body shape, with the preferred body configuration varying as a function of the
      ethnicity of the figure being rated. In addition, there was a strong positive
      correlation between ratings of attractiveness and health. These findings are
      discussed in relation to the interplay between culture and evolution in
      determining ideals of attractiveness.

PMID- 18625081
TI  - The Arabidopsis thaliana response regulator ARR22 is a putative AHP phospho
      histidine phosphatase expressed in the chalaza of developing seeds.
AB  - BACKGROUND: The Arabidopsis response regulator 22 (ARR22) is one of two members
      of a recently defined novel group of two-component system (TCS) elements. TCSs
      are stimulus perception and response modules of prokaryotic origin, which signal
      by a His-to-Asp phosphorelay mechanism. In plants, TCS regulators are involved in
      hormone response pathways, such as those for cytokinin and ethylene. While the
      functions of the other TCS elements in Arabidopsis, such as histidine kinases
      (AHKs), histidine-containing phosphotransfer proteins (AHPs) and A-type and B
      type ARRs are becoming evident, the role of ARR22 is poorly understood. RESULTS:
      We present evidence that ARR22 is a preferentially cytoplasmic protein,
      exclusively expressed in the chalaza of developing seeds. ARR22 specifically
      interacts with AHP2, AHP3 and AHP5 in yeast and living plant cells. Two new loss
      of-function alleles, arr22-2 and arr22-3, were isolated and characterized. With
      respect to their morphology and metabolite status, no significant difference in
      the developing seeds of the arr22 mutants was observed compared to wild type. The
      genetic complementation of the arr22 mutants with a genomic ARR22 fragment
      resulted in plants (arr22/gARR22) with a pleiotropic phenotype of different
      penetrance. This phenotype was not observed when the phosphorylatable Asp74 of
      ARR22 was changed to either a dominant-active Glu or a dominant-inactive Asn. The
      phenotype of the arr22/gARR22 plants was comparable to that of multiple ahk, ahp
      and B-type arr mutants. CONCLUSION: Our results favor the model that ARR22 acts
      as a phospho-histidine phosphatase on specific AHPs in the cytoplasm of
      Arabidopsis chalaza cells. The lack of any aberrant morphological and metabolite
      phenotype in the seeds of the arr22 mutants indicates that ARR22 is probably
      primarily responsible for the fine tuning of specific branches of chalaza-based
      TCS signalling. Even when slightly mis-expressed, ARR22 interferes with hormone
      homeostasis in non-chalaza tissues. Our data indicate that the chromatin status
      might play a crucial role in maintaining the chalaza-restricted expression of
      ARR22.

PMID- 18625083
TI  - Latent variable models for multivariate longitudinal ordinal responses.
AB  - The paper proposes a full information maximum likelihood estimation method for
      modelling multivariate longitudinal ordinal variables. Two latent variable models
      are proposed that account for dependencies among items within time and between
      time. One model fits item-specific random effects which account for the between
      time points correlations and the second model uses a common factor. The
      relationships between the time-dependent latent variables are modelled with a non
      stationary autoregressive model. The proposed models are fitted to a real data
      set.

PMID- 18625085
TI  - Risk factors for falling among community-dwelling seniors using home-care
      services: an extended hazards model with time-dependent covariates and multiple
      events.
AB  - The identification of risk factors for falls in longitudinal studies becomes
      difficult because of exposures that change during the follow-up and also because
      individual subjects may experience an event more than once. These issues have
      been neglected and improper statistical techniques have been used. The typical
      approaches have been to report the proportion of fallers or the time to first
      fall. Both avoid the underlying assumption of independence between events and
      discard pertinent data. We review the existing methods and propose a Cox hazards
      extension. We exemplify it in the study of potential risk factors associated with
      all falls in 959 seniors. Finally, we compare the results of the proposed Wei,
      Lin, & Weissfeld (WLW) method with those of several other techniques. Stable
      exposure variables measured at baseline and updated time-varying exposures
      include socio-demographic characteristics, BMI, nutritional risk, alcohol
      consumption, home hazards, gait and balance, and medications. Results demonstrate
      that the usual methods of analyzing risk factors for falling are inappropriate,
      as they produce considerable biases relative to the WLW model using time
      dependent covariates. Results also show that modeling for first events may be
      inefficient, given that the risk of occurrence varies between falls.

PMID- 18625084
TI  - Effects of psychological therapies in randomized trials and practice-based
      studies.
AB  - BACKGROUND: Randomized trials of the effects of psychological therapies seek
      internal validity via homogeneous samples and standardized treatment protocols.
      In contrast, practice-based studies aim for clinical realism and external
      validity via heterogeneous samples of clients treated under routine practice
      conditions. We compared indices of treatment effects in these two types of
      studies. METHOD: Using published transformation formulas, the Beck Depression
      Inventory (BDI) scores from five randomized trials of depression (N = 477
      clients) were transformed into Clinical Outcomes in Routine Evaluation-Outcome
      Measure (CORE-OM) scores and compared with CORE-OM data collected in four
      practice-based studies (N = 4,196 clients). Conversely, the practice-based
      studies' CORE-OM scores were transformed into BDI scores and compared with
      randomized trial data. RESULTS: Randomized trials showed a modest advantage over
      practice-based studies in amount of pre-post improvement. This difference was
      compressed or exaggerated depending on the direction of the transformation but
      averaged about 12%. There was a similarly sized advantage to randomized trials in
      rates of reliable and clinically significant improvement (RCSI). The largest
      difference was yielded by comparisons of effect sizes which suggested an
      advantage more than twice as large, reflecting narrower pre-treatment
      distributions in the randomized trials. CONCLUSIONS: Outcomes of completed
      treatments for depression in randomized trials appeared to be modestly greater
      than those in routine care settings. The size of the difference may be distorted
      depending on the method for calculating degree of change. Transforming BDI scores
      into CORE-OM scores and vice versa may be a preferable alternative to effect
      sizes for comparisons of studies using these measures.

PMID- 18625086
TI  - Gender and the smoking behaviour of Ethiopian immigrants in Toronto.
AB  - The objective of this paper is to present descriptive data on gender and smoking
      among Ethiopian immigrants in Toronto, Canada. The study used a cross-sectional
      epidemiological survey design (N = 342). The main outcome measures identified
      subjects as current (regular or occasional) smokers, daily smokers and former
      smokers. Overall, 20.8% of the individuals in the sample were current smokers and
      15.7% were daily smokers. Although smoking rates (current and daily) were
      significantly higher among males compared to females, nearly twice as many female
      as male daily smokers reported that they began smoking post-migration (60.0% vs.
      30.2%). Furthermore, 80.0% of female compared to nearly 56% of male daily smokers
      reported that they were smoking more post-migration. A significantly higher
      proportion of males compared to females were former daily smokers (17.8% vs.
      4.4%). These findings present a challenge for public health professionals in
      terms of preventing the adoption of smoking among Ethiopian females and
      facilitating smoking cessation among Ethiopian males. Correlates with current
      smoking suggested that smoking prevention and cessation programs in newcomer
      immigrant communities may benefit from incorporating social, economic and
      religious contexts of these newcomers' lives from a gender-specific perspective.

PMID- 18625087
TI  - Ethnicity and mental health: conceptualization, definition and operationalization
      of ethnicity from a Canadian context.
AB  - The current study provides a critical review of Canadian studies on ethnicity and
      mental health with respect to the definition, conceptualization and
      operationalization of ethnicity. It provides a discussion on the methodological
      issues related to these factors and their implications to guide future research
      and enable comparability of results across studies. Sociological Abstracts,
      PsycINFO, MEDLINE and CINAHL were used to identify relevant Canadian articles
      published between January 1980 and December 2004. The review highlights a number
      of key issues for future researchers to consider such as the need for: 1) clear
      rationales as to why ethnicity is important to their outcome of interest; 2)
      clarity on the definition of ethnicity, which affects its conceptualization and
      operationalization; 3) a theoretically driven conceptualization of ethnicity,
      which should be related to the research question of interest; and 4) clear
      rationales for the decisions made regarding the data source used, the
      operationalization of ethnicity, and the ethnic categories included in their
      studies.

PMID- 18625088
TI  - Association of comorbid mood disorders and chronic illness with disability and
      quality of life in Ontario, Canada.
AB  - Mood disorders are more prevalent in individuals with chronic physical illness
      compared to individuals with no such illness. These disorders amplify the
      disability associated with the physical condition and adversely affect its
      course, thus contributing to occupational impairment, disruption in interpersonal
      and family relationships, poor health and suicide. This study used data collected
      in the Canadian Community Health Survey, cycle 3.1 (2005) to examine factors
      associated with comorbid mood disorders and to assess their association with the
      quality of life of individuals living in Ontario. Results indicate that
      individuals with chronic fatigue syndrome, fibromyalgia, bowel disorder or
      stomach or intestinal ulcers had the highest rates of mood disorders. The odds of
      having a comorbid mood disorder were higher among women, the single, those living
      in poverty, the Canadian born and those between 30 and 69 years of age. The
      presence of comorbid mood disorders was significantly associated with short-term
      disability, requiring help with instrumental daily activities and suicidal
      ideation. Health care providers are urged to proactively screen chronically ill
      patients for mood disorders, particularly among the subgroups found to have
      elevated risk for these disorders.

PMID- 18625089
TI  - Costs associated with mood and anxiety disorders, as evaluated by telephone
      survey.
AB  - Costing studies are central to health policy decisions. Available costing
      estimates for mood and anxiety disorders in Canada may, however, be out of date.
      In this study, we estimated a set of direct health care costs using data
      collected in a provincial telephone survey of mood and anxiety disorders in
      Alberta. The survey used random digit dialing to reach a sample of 3394 household
      residents aged 18 to 64. A telephone interview included items assessing costs
      without reference to whether these were incurred by the respondent, government or
      a health plan. The survey interview also included the Mini Neuropsychiatric
      Diagnostic Interview (MINI). Costs for antidepressant medications appear to have
      increased since the last available estimates were published. Surprisingly, most
      medication costs for antidepressants were incurred by respondents without an
      identified disorder. Also, an unexpectedly large proportion of medication costs
      were for psychotropic medications other than antidepressants and anxiolytic
      sedative-hypnotics. These results suggest that major changes have occurred in the
      costs associated with antidepressant treatment. Available cost-of-illness data
      may be outdated, and some assumptions made by previous studies may now be
      invalid.

PMID- 18625090
TI  - [Measuring quality of life in palliative care].
AB  - This paper describes the process followed to create and validate the Portuguese
      version of a quality of life measurement instrument for patients in palliative
      care. After a literature review about the measurement of the quality of life in
      this particular and very specific kind of patients, we opt by the Irene
      Higginson's measurement instrument called Palliative Care Outcome Scale (POS). It
      has been selected as the one most appropriate to Portuguese patients' reality.
      For the creation of the Portuguese version we followed the recommended
      methodologies for the forward-backward translations. These methodologies allow us
      to determine semantic and linguistic equivalences of health outcomes measurement
      instruments. The validation was performed on a sample of 104 cancer patients aged
      between 40 and 85 years old. 70% were female, 29% had lung cancer, 46% breast
      cancer and 22% had melanoma. Content validity was assured by two cognitive
      debriefing tests, respectively performed in oncologists and in patients.
      Construct validation allow us to find five ortogonal factors, including
      'emotional well being' (19.7% of variance explained), 'consequences of the
      disease in life' (18.2%), 'received information and support' (11.7%), 'anxiety'
      (10.1%), and 'burden of illness' (9.8%). Criterion validity was tested by
      comparing the results obtained by POS to the ones obtained by the EORTC QLQ-C30,
      a genetic instrument especially designed for cancer patients. The found
      correlation values were moderated to strong and ranged from 0.51 to 0.63. The
      reliability of the Portuguese version was assured through the reproducibility
      test and the search for the internal consistency. The scores obtained by a one
      week testrestest ranged from 0.66 to 1.00. Cronbach's alpha was 0.68, acceptable
      and allowing us to consider POS as a unique index Time responsiveness and
      diagnosis responsiveness were also analysed. Comparing values measured with a one
      month interval showed sensibility to the lack of the quality of life felt by
      patients. This measurement instrument was also sensitive to the various
      pathologies. In conclusion, we may defend the quality of the performance of the
      Portuguese version of the POS. This version may be used to prospectively assess
      the palliative care on advances cancer patients.

PMID- 18625091
TI  - [Cancer patients quality of life, measured by themselves and proxys].
AB  - AIMS: Health Related Quality of Life (HRQoL) is an essential factor for cancer
      patients, particularly in the evaluation of the care's. Most of the information
      that health care providers have is given by the patient. Family can also provide
      information about them, appealed or not and the quality of such information isn't
      studied for Portuguese population. The aim of this study was to examine whether
      proxies can provide useful information on HRQoL of cancer patients. METHODS: We
      studied a sample of 176 ambulatory cancer patients and those 176 respective
      proxies (family) from Medical Oncology Department. A sociodemographic
      characterization was made for the simple and a clinical characterization was made
      only for cancer patients. To measure HRQoL were used the EORTC QLQ-C30. Beyond
      descriptive techniques, the statistical analysis was done using Interclass
      Correlation (ICC) and Pearson Correlation (r). RESULTS: We found moderate to good
      agreement (ICC ranged from 0.55 to 0.82, as well as the Pearson correlation)
      between responses from patients and those from their proxies for the QLQ-C30
      scales. Proxies' group considered patients as having higher degree of fatigue,
      pain and diarrhea and a more impaired physical and emotional functioning, worse
      global QoL and total score. Statistically significant differences between
      patients' and proxies' evaluations were found for these subscales. None of the
      patients or proxies characteristics showed any relationship with the agreement
      between patient and proxy QoL evaluations'. CONCLUSION: The results suggest that
      proxies only provide valid and useful information about cancer patients QoL for
      QLQ-C30 domains where the agreement between QoL's responses were high and the
      means diferrence not significant. For using a HRQoL instrument taking into
      account as source the proxy, is necessary to recognize the agreement of the
      HRQoL's domains of the instrument. In this case, for several domains of QLQ-C30
      the means difference was statistically significant, so, the instrument should be
      used with caution for physical and emotional functioning, global QoL fatigue,
      pain, diarrhoea and total QoL. Proxies are a frequent and a mandatory source of
      information about patient's status, particularly in palliative care. On a
      clinical point of view, the knowledge of these differences is very important for
      that such information be ponderous and contextualized in order to improve better
      care to the patients.

PMID- 18625092
TI  - [Cyto-histological correlation of malignant thyroid nodules: clinical factors as
      predictors of malignancy].
AB  - INTRODUCTION: Fine-needle aspiration (FNA) is routinely used to distinguish
      benign from malignant tumors in thyroid nodules. Most benign or malignant
      diagnosis are confirmed by histology, but for suspected malignancies (Follicular
      neoplasm and Hurthle-cell neoplasm histology is always required. Some clinical
      factors have been identified as predictors of malignancy in the suspicious cases
      with eventual interest for treatment options. AIM: To determine the correlation
      between FNA and histological diagnosis in malignant tumors at Hospital de Egas
      Moniz. Identify factors that may influence the risk of malignancy in patients
      with suspected malignancies (Tumor size, gender and age group). METHODS:
      Retrospective study of patients with malignant or suspected malignant tumors
      diagnosed by FNA in the institution. All patients were subsequently diagnosed by
      histology and age, sex and tumor dimension were also recorded. RESULTS: From 2685
      FNA performed between October 1996 and June 2005, 68 patients were considered for
      analysis, which have been diagnosed as malignant (34 patients) or suspicious of
      malignancy (34 patients). Only in one case didn't the histology confirm the
      cytological diagnosis of malignancy. Among the suspicious FNA 25 were benign (23
      female and 2 male, mean age of 54,3 +/-17 yo and mean nodule size of 2,8 +/- 1,8
      cm) and nine (26,5%) were malignant (all female, mean age 68,3 +/- 13 yo and mean
      nodule size 2,67 +/- 1,5 cm). Nodules with 2 cm or more were malignant in 37% (vs
      8% when < 2 cm; P=0,033) and patients with 50 yo or more revealed to be malignant
      in 33% (vs 10% when < 50 yo; P=0,019), therefore nodule size and age were
      identified as independent predictors for malignancy. CONCLUSIONS: There was a
      strong correlation between cytological and histological diagnoses. Age and tumor
      size were strong predictors of malignancy in patients with suspected
      malignancies. This and other factors may be useful to identify patients who may
      benefit from a total thyroidectomy as the first intervention.

PMID- 18625093
TI  - [Coping in transplantated patients].
AB  - The theoretical model of coping mechanisms (CM), is based on a discussion between
      it's main determinant factors: individual and situational (related to the 2
      approaches of coping: dispositional and constitutional). Actually the most used
      classification of CM is based on the division of CM in two main dimensions:
      coping focused on emotions and coping focused on problem resolution. It is
      essential that classification methods of CM have in consideration the coexistence
      of stable dispositional elements with a situational variability. Some instruments
      to evaluate CM are introduced, based on different theories. Coping can influence
      health threw different mechanisms (neuroendocrine system, health threatening
      behaviours and adherence) and is included in two of the more important
      theoretical models applied to health (Moos & Schafer's and Leventhal's). Based on
      a systematic literature review we concluded that the most prevalent CM in pre
      transplantation period are acceptance, active coping, seeking support, and the
      less used are self-blame and avoidance. In post transplantation period the more
      prevalent CM continue to be active coping and seeking support associated to
      confrontation, selfconfidence, religion and coping focused in the problem.
      Evasive, emotive and fatalistic CM are associated to less control sensed by
      patients. Confrontation is associated to a better quality of life and avoidance
      to a reduction of quality of life and higher depression levels and denial to non
      adherence increase. Control sensed by patients, CM related to the expression of
      emotions and denial change threw clinical evolution of transplanted patients.

PMID- 18625094
TI  - [Changes of food habits during pregnancy and breast-feeding].
AB  - Many women have incorrect notions of what they can eat during pregnancy and/or
      breast-feeding, due to preconceived ideas or myths related with the ingestion of
      some types of food. The aim of this study was to evaluate the alteration of food
      habits in pregnant women and identifying the myths related with eating habits in
      pregnant and breast-feeding women. A questionnaire of food habits alteration in
      pregnant women, the origin of the alterations and the reasons for such, as well
      as the eventual knowledge about which food interferes with pregnancy and/or
      breast-feeding and the Information about the alteration of weight during
      pregnancy and relevant clinical history were asked. The data were analysed though
      SPSS (Statistical Package for the Social Sciences), version13.0 for Windows. This
      study shows that although the majority of the alterations of food eating habits
      were done in a proper manner, there are still many inadequate or unnecessary food
      habit changes done in an empirical form, or based on myths, or indicated by some
      health professionals.

PMID- 18625095
TI  - [Fluid intake and overweight risk in children].
AB  - The global prevalence of overweight and obesity in children is growing. A number
      of eating patterns have been associated with different risks of overweight. Sugar
      sweetened beverages have received considerable attention as potential sources of
      energy in liquid form that could be responsible for body weight gain. OBJECTIVE:
      Evaluate the association between fluid intake and overweight in schoolchildren.
      MATERIAL AND METHODS: The final sample of the study includes 1675 children
      schools between 5 and 10 years old, after excluding dietary misreporting and
      questionnaires with incomplete information. After parental written consent,
      children's height and weight were measured according to international standards,
      and body mass index was calculated. The definition of overweight was based on
      average centiles according to the International Obesity Task Force cutoffs. We
      administered a questionnaire to parents that included information about physical
      activity, dietary intake (food frequency questionnaire that included information
      on milk, vegetable soup, cola, ice-tea and other sugar-sweetened beverages) and
      socio-demographic information. Adjusted odds ratios were computed using logistic
      regression. RESULTS: We found a high prevalence of overweight (including obesity)
      being 36,6% for girls, and 38,8% for boys. In girls the probability of being
      overweight increased significantly for those having low consumption of vegetable
      soup (equal or lower tan the median) compared to those with high consumption
      (higher than the median), even after adjusting for confounders (OR = 0,68, CI 95%
      0,48-0,96, p = 0,030). We didn't find any significant association between sugar
      sweetened beverages and milk intake with overweight in both genders. CONCLUSION:
      In girls, high vegetable soup consumption significantly decreased the probability
      of being overweight, independently of other characteristics.

PMID- 18625096
TI  - [Tarlov's cyst: definition, etiopathogenesis, propaedeutic and treatment].
AB  - Tarlov's cyst or perineurial cyst is disease on portion of the posterior nerve
      root in lumbo-sacral region. The lack of knowledge of physicians around the world
      about Tarlov's cyst as to their nature, significance and treatment also with
      differential diagnostics to radiculopathy in legs. With review of literature
      discuss about definition, etiopathogenesis, diagnostic investigation and
      treatment clinic and/or surgery. The pathogenesis Tarlov's cyst remains unclear;
      several cases have history of the trauma, old hemorrhage, congenital and
      iatrogenic. Cysts provoke low back pain, sacral radiculopathy, dyspareunia,
      urinary incontence. The magnetic resonance imaging is now the gold standard to
      diagnose cysts. The treatment is clinic or surgery depending neurologics finding
      and neuroimage.

PMID- 18625097
TI  - [Chronic viral hepatitis: protocol proposal for the management of cirrhosis].
AB  - Cirrhosis is the terminal phase of hepatic fibrosis, that leads to impaired
      hepatic function and blood flow. Liver cirrhosis is the final stage of many
      hepatic diseases characterized by chronic cellular destruction. The complications
      of liver cirrosis are the result of the hepatocellular lesion and portal
      hypertension. The most frequent complications are ascites, spontaneous bacterial
      peritonitis, hepatic encephalopathy, gastroesophageal varices, portal
      hypertensive gastropathy, hypersplenism, hepatocellular carcinoma, methabolic
      disorders, hepatorenal syndrome and hepatopulmonary syndrome. We review the
      current approach of cirrhosis and its complications in order to improve the
      prevention and therapeutics of this frequent disease.

PMID- 18625098
TI  - [Aging and blood pressure].
AB  - High blood pressure is a major risk factor of cardiovascular diseases and has a
      high prevalence in the older individuals becoming in a risk factor associated
      with high cardiovascular mortality and morbidity among these population. This
      study has the objective to analyze the changes in the cardiovascular system
      inherent to the aging process, that provoke the increase of blood pressure levels
      with the advance of age and that can origin hypertension. With the aging process,
      changes in the anatomy and cardiovascular physiology occur, even in the absence
      of illness. High blood pressure is characterized as a systemic condition that
      involves the presence of structural changes of the arteries and the myocardium,
      associated to an endotelial and baroreceptors dysfunction.

PMID- 18625099
TI  - [Lupus erythematosus].
AB  - Systemic Lupus Erythematosus (SLE) is an auto-imune disorder, with multiple organ
      involvement, characterized by vascular and connective tissue inflammation, as
      well as antinuclear antibodies (ANA). We report a case of a black teenager with a
      past of arthritis of knees, fever and astenia during the year previous to this
      admission. She was admitted to the Pediatric Intensive Care Unit (PICU) for
      bilateral Streptococcus pneumoniae pneumonia complicated by pleural effusion. She
      also had generalized edema and macroscopic hematuria. She was started on
      antibiotics, with improvement. The studies were compatible with active SLE,
      poliserositis, nephrotic proteinuria, lupic nephritis class IV and serious
      anemia. During the admission, she had symptomatic hypertension with tonic-clonic
      seizure. She was transferred to Italy, clinically stable, medicated with
      steroids, anti-hypertensive and anti-convulsant drugs.

PMID- 18625100
TI  - Assessment and management of breakthrough pain in cancer patients: current
      approaches and emerging research.
AB  - Cancer pain is highly prevalent and often severe. Fortunately, most cancer pain
      can be readily managed, with up to 90% of patients responding well to standard
      interventions. However, breakthrough cancer pain-brief flares of severe pain
      superimposed on baseline pain-is common, difficult to manage, and often
      negatively impacts patients' quality of life. Breakthrough cancer pain is
      traditionally managed with oral, immediate-release opioids. However, because of
      its sudden onset and severity, oral opioids often fall short of providing
      adequate control. Research into novel approaches to pain management has
      identified several innovative strategies for this difficult cancer pain problem.
      We describe current approaches to assess, define, characterize, and treat
      breakthrough cancer pain, and summarize recent clinical research on novel agents,
      novel routes of drug delivery, and other advances in its management.

PMID- 18625101
TI  - Intrathecal analgesia for refractory cancer pain.
AB  - The use of intrathecal analgesics is an important treatment consideration for
      many patients with chronic cancer pain. This review describes the various opioid
      and nonopioid analgesics that have been used in this setting, including morphine,
      hydromorphone, fentanyl, meperidine, methadone, sufentanil, local anesthetics,
      clonidine, ketamine, baclofen, midazolam, betamethasone, and octreotide. We
      discuss available evidence for their analgesic and adverse effects.

PMID- 18625102
TI  - Pain management in palliative care oncology patients.
AB  - Palliative care is an interdisciplinary approach to relieving aversive symptoms
      in people with life-threatening illnesses; it aims to improve the lives of
      patients and their loved ones, the "patient-family unit." Palliative care should
      occur in parallel with all other medical interventions. Indeed, good symptom
      management is important in helping patients cope with the unpleasantness
      associated with potentially curative or life-prolonging interventions; it is
      absolutely essential near the end of life. Unrelieved pain is the symptom that
      people fear the most. In most cases, adequate pain relief can be achieved with
      systemic medications alone. When systemic medications fail, due to inadequate
      analgesia or burdensome side effects, invasive techniques may complement, or
      replace, systemic therapy. Using a case-based format, we illustrate some complex
      issues that clinicians face and offer strategies to improve the lives of oncology
      patients with pain.

PMID- 18625103
TI  - Assessment and management of psychiatric issues during cancer treatment.
AB  - Since its beginnings in the mid-1970s, the field of psycho-oncology has developed
      rapidly. A substantial body of literature has evolved toward identifying key
      issues for psychiatric treatment and care management of cancer patients. The
      spectrum of cancer care encompasses patient experiences through initial
      diagnosis, active treatment, after-care and survivorship, as well as palliative
      care and end-of-life. This article highlights recognition and management of
      psychiatric syndromes in the context of cancer care.

PMID- 18625104
TI  - Cancer pain: perspectives of a medical oncologist.
AB  - Pain is highly prevalent in cancer patients and primarily managed by medical
      oncologists. This article reviews cancer pain syndromes related to cancer and
      sequelae of treatment. We discuss the assessment and treatment of cancer pain
      with pharmacotherapy and chemotherapy, and the role of pain specialists. There
      are numerous barriers to care, which arise from both the physician and patient.
      We review approaches that diminish these barriers to improve treatment of cancer
      pain.

PMID- 18625105
TI  - Burning mouth syndrome.
AB  - Burning mouth syndrome (BMS) is a chronic disease characterized by burning of the
      oral mucosa associated with a sensation of dry mouth and/or taste alterations.
      BMS occurs more frequently among postmenopausal women. The pathophysiology of the
      disease is still unknown, and evidence is conflicting; although some studies
      suggest a central origin, others point to a peripheral neuropathic origin. The
      efficacy of some medications in the treatment of BMS suggests that the
      dopaminergic system may be involved.

PMID- 18625106
TI  - Ophthalmoplegic migraine: still a diagnostic dilemma?
AB  - The term ophthalmoplegic migraine (OM) was first coined by Charcot in 1890. This
      condition was included as a migraine variant in the first Headache Classification
      of the International Headache Society in 1988. Based on postcontrast enhancement
      seen on MRI in some patients who were diagnosed with OM, there was a suggestion
      that this could be an inflammatory/demyelinating disorder; therefore, it was
      moved out of the "migraine" group and repositioned as a "neuralgia" in the
      revised 2004 classification. However, there have been subsequent reports in the
      literature in which there was no enhancement on postcontrast MRI. Based on a
      survey of literature on OM in the post-imaging era, this article highlights the
      fact that enhancement on magnetic resonance is not a sine qua non for the
      diagnosis of OM. Some diagnostic dilemmas are discussed, and a protocol is
      included for documentation of clinical findings in future case reports on a
      prospective basis. Hopefully, this will help in modification of the criteria,
      better understanding the etiology, correct diagnosis, and determining appropriate
      treatment for OM.

PMID- 18625107
TI  - The metabolic headaches.
AB  - This review discusses headaches secondary to disorders of homeostasis, formerly
      known as "headaches associated with metabolic or systemic diseases." They include
      the headaches attributed to 1) hypoxia and/or hypercapnia (high altitude, diving,
      sleep apnea); 2) dialysis; 3) arterial hypertension; 4) hypothyroidism; 5)
      fasting; and 6) cardiac cephalalgia. For each headache type, we discuss the
      clinical features and diagnosis, as well as therapeutic strategies.

PMID- 18625108
TI  - Headache and the eye.
AB  - Because of the inextricable link between the eyes and headaches, ophthalmologists
      are often the first physicians to evaluate patients with headaches, eye pain, and
      headache-associated visual disturbances. Although ophthalmic causes are sometimes
      diagnosed, eye pain and visual disturbances are often neurologic in origin. Many
      primary headache disorders have ophthalmic features, and secondary causes of
      headache frequently involve the visual system. Both afferent and efferent
      symptoms and signs are associated with headache disorders. Moreover, the frontal
      or retro-orbital pain of some primary ophthalmic conditions may be mistaken for a
      headache disorder, particularly if the ophthalmologic examination is normal. This
      article reviews common ocular conditions that are associated with head pain, and
      some secondary causes of headache with neuro--ophthalmic manifestations.

PMID- 18625109
TI  - Headache secondary to psychiatric disorders.
AB  - Recent literature shows an interest in the relationship between psychiatric
      disorders and headache. This relationship is complex and multifaceted, with
      existing studies confirming high rates of comorbidity between psychiatric
      disorders (especially depression and anxiety) and migraine and tension-type
      headache, implicating comorbid psychiatric disorders as risk factors for headache
      progression and chronification, and underscoring the need for assessment and
      treatment of relevant disorders. A smaller amount of literature has focused on
      headache that presents exclusively during and secondary to a psychiatric
      disturbance; this phenomenon has been termed "headache attributed to psychiatric
      disorder." We review recent developments in the relationship between psychiatric
      conditions and headache, with a particular focus on headaches attributed to
      psychiatric disorders, and discuss needed areas for future research.

PMID- 18625110
TI  - Caffeine and headaches.
AB  - Caffeine is the most widely consumed psychostimulant drug in the world. With
      intermittent exposures, caffeine may act as a mild analgesic for headache or as
      an adjuvant for the actions of other analgesics. Chronic repetitive exposures to
      caffeine increase the risks for development of analgesic-overuse headache,
      chronic daily headache, and physical dependency. Cessation of caffeine use after
      chronic exposures leads to a withdrawal syndrome with headache as a dominant
      symptom. At dosages achieved by common dietary intake, caffeine acts as a potent
      antagonist of central and peripheral nervous system adenosine receptors. The
      complex effects of caffeine on headache disorders suggest important roles for
      adenosine in these disorders and in the induction of caffeine dependency.

PMID- 18625111
TI  - When good cholesterol turns bad: the evolving saga of CETP inhibitors and
      clinical strategies to elevate high-density lipoprotein.

PMID- 18625112
TI  - Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus.
AB  - Insulin resistance is a characteristic feature of type 2 diabetes mellitus,
      obesity, and the metabolic syndrome. Increased intracellular fat content in
      skeletal muscle and liver associated with insulin resistance has led to the
      hypothesis that a mitochondrial defect in substrate oxidation exists in disorders
      of insulin resistance. In vivo measurements of metabolic fluxes through the
      tricarboxylic acid and oxidative phosphorylation with magnetic resonance
      spectroscopy have demonstrated multiple defects in mitochondrial function in
      skeletal muscle. A decrease in mitochondrial density and mitochondrial copy
      number has been reported in insulin-resistant individuals. However, these
      findings have not been a consistent observation in all studies. Similarly, an
      intrinsic functional defect in mitochondrial adenosine triphosphate production
      synthesis has been reported in some but not all studies. This review summarizes
      evidence that implicates a defect in mitochondrial oxidative phosphorylation and
      its relationship to insulin resistance in common metabolic diseases characterized
      by impaired insulin action.

PMID- 18625113
TI  - Beta-cell failure in type 2 diabetes mellitus.
AB  - Diabetes mellitus has been defined as a "group of metabolic diseases
      characterized by hyperglycemia resulting from defects in insulin secretion,
      insulin action, or both" and encompasses a wide range of heterogeneous
      conditions. Common type 2 diabetes mellitus (T2DM) results from a combination of
      genetic and acquired factors. However, lifestyle factors, particularly overeating
      and physical inactivity, are the major clinical determinants of T2DM. Insulin
      resistance is a common feature of T2DM, but it is unlikely to cause T2DM unless
      progressive loss of beta-cell function develops. Significant reduction in beta
      cell function is already present at the time of T2DM diagnosis, and it
      continuously declines irrespective of treatment. As such, the progressive loss of
      beta-cell function dictates the rate of worsened glycemic control. Development of
      progressive deterioration accelerates via gluco- and lipotoxicity, loss of beta
      cell function, and shrinkage of beta-cell mass. Understanding the causes for beta
      cell failure is therefore of capital importance to develop new and more effective
      therapeutic strategies.

PMID- 18625114
TI  - Ectopic fat and insulin resistance.
AB  - Ectopic fat is defined by the deposition of triglycerides within cells of non
      adipose tissue that normally contain only small amounts of fat. Over the past
      decade, magnetic resonance spectroscopy has been used extensively for noninvasive
      quantification of intramyocellular, intrahepatocellular, and more recently
      myocardial and pancreatic lipids. In liver and muscle, triglyceride content
      usually correlates with whole-body and tissue-specific insulin sensitivity.
      However, fat mass and oxidative capacity influence this relationship, indicating
      that ectopic lipid content is not the only factor that explains insulin
      resistance. Ectopic lipids may rather serve as biomarkers of the balance between
      metabolic supply and demand in different states of insulin sensitivity.
      Consequently, ectopic lipid concentrations, particularly in the liver, decrease
      with lifestyle- or drug-induced improvement of insulin sensitivity.

PMID- 18625115
TI  - Genes and type 2 diabetes mellitus.
AB  - In 2007, five whole genome-wide association studies were published on the
      genetics of type 2 diabetes mellitus (T2DM), followed by the discovery of 11
      genes consistently associated with T2DM. This breakthrough provided the first
      glimpses of a complete picture of the disease's genetic complexity. Currently, we
      are only beginning to understand how DNA methylation, histone acetylation, and
      deacetylation may introduce epigenetic changes throughout one's lifetime. Such
      changes may influence age-related modifications in gene-expression that
      contribute to age-related diseases. In the future, the possibility of whole
      genome DNA methylation studies may elucidate the extent of these epigenetic
      effects. This article reviews genes that have recently been determined to be
      associated with T2DM.

PMID- 18625116
TI  - What are the long-term cardiovascular effects of treatment with rosiglitazone?

PMID- 18625117
TI  - The role of aldosterone in cardiovascular disease in people with diabetes and
      hypertension: an update.
AB  - The role of mineralocorticoids in the development of cardiovascular disease
      (CVD), cardiometabolic syndrome, type 2 diabetes mellitus, chronic kidney disease
      (CKD), and hypertension is a growing field of interest. Aldosterone, mainly
      through nongenomic actions that result in proliferation, fibrosis, inflammation,
      and tissue remodeling, has been linked to CVD and CKD. Increased circulating
      aldosterone is also associated with insulin resistance and impaired glucose
      homeostasis that contribute to the development of endothelial dysfunction,
      atherosclerosis, and kidney disease. Aldosterone-induced oxidative stress and
      inflammation play a key role in impairing insulin signaling. Mineralocorticoid
      receptor blockade restores insulin sensitivity, counterbalances the deleterious
      cardiovascular and renal effects of aldosterone, and emerges as an alternative to
      improve blockade of the renin-angiotensin-aldosterone system, which potentially
      could contribute to reduce the burden of CVD and CKD.

PMID- 18625118
TI  - Vascular compliance in hypertension: therapeutic implications.
AB  - One of three adults and more than 7 of 10 older persons in the United States have
      hypertension. Of those receiving antihypertensive medication, more than 40% have
      inadequate blood-pressure control. The predominant subtype of hypertension among
      older adults is isolated systolic hypertension, which results from stiffening of
      the wall of the aorta due to various factors, including loss and fragmentation of
      elastin, increased collagen synthesis, endothelial dysfunction, and higher levels
      of inflammatory cytokines. Analysis of the peripheral pulse waveform has become
      widely used as a surrogate marker of central aortic stiffness and a predictor of
      future cardiovascular disease events. It is a matter of debate whether increased
      pulse pressure in older adults results primarily from stiffening of the aortic
      wall and premature reflected pressure waves from peripheral arteries or increased
      forward pressure waves from a reduced aortic diameter. Anti-stiffening strategies
      depend on lifestyle changes and pharmacotherapy.

PMID- 18625119
TI  - Antihypertensive medications and their effects on lipid metabolism.
AB  - Hypertension and hyperlipidemia are interrelated and share common
      pathophysiologic mechanisms, such as insulin resistance and endothelial
      dysfunction. Accumulating evidence shows that it is important to regulate
      hypertension and hyperlipidemia to reduce cardiovascular risk. However,
      medications such as beta-blockers and thiazide diuretics, which are widely used
      for blood pressure regulation, are known to have several metabolic side effects.
      Despite deleterious effects on glucose metabolism and lipid metabolism, these
      medications have been proven to reduce cardiovascular risk. On the other hand,
      calcium channel blockers, angiotensin-converting enzyme inhibitors, and alpha
      blockers have either no effect or favorable effects on the lipid profile. This
      review outlines the need to control hypertension, options for several
      antihypertensive medications, their differing effects on lipid metabolism, and
      the clinical implications of their effects on lipid parameters.

PMID- 18625121
TI  - Increased insulin resistance in young adults born with very low birth weight.

PMID- 18625120
TI  - Posttransplant diabetes and hypertension: pathophysiologic insights and
      therapeutic rationale.
AB  - New-onset diabetes after transplantation and hypertension are very common after
      renal transplantation and are associated with adverse graft and cardiovascular
      outcomes. A thorough understanding of the unique factors that operate in renal
      transplant recipients is essential for the proper evaluation and management of
      these important disorders. This review outlines the pathogenesis, diagnostic
      workup, and therapeutic rationale for diabetes and hypertension after
      transplantation.

PMID- 18625122
TI  - Effects of chronic hyperinsulinemia in insulin-resistant patients.
AB  - Selective insulin resistance influences pathogenesis and treatment of type 2
      diabetes and metabolic syndrome. Downregulation of the antiatherogenic pathway
      and maintained activity of the proatherogenic and cancerogenic pathways lead to
      atherosclerosis and cancer. Exogenous insulin added to "compensatory"
      hyperinsulinemia might worsen the primary end points, resulting in potential
      increase in cardiovascular and cancer events in spite of improvement of surrogate
      metabolic end points. Conversely, metformin can improve primary and surrogate end
      points.

PMID- 18625123
TI  - Effects of insulin and free fatty acids on matrix metalloproteinases.
AB  - To investigate if increased activation of matrix metalloproteinases (MMPs) may
      contribute to the large cardiovascular risk associated with obesity-related
      insulin resistance, we examined the effects of physiologically elevated levels of
      insulin and free fatty acid (FFA) on three MMPs and their physiologic inhibitors
      (tissue inhibitors of MMP ) in aortic tissue of male rats during euglycemic
      hyperinsulinemic clamping. Hyperinsulinemia increased the active forms of MMP-2
      (approximately sixfold), MMP-9 (approximately 13-fold), and membrane type 1-MMP
      (MT1-MMP; approximately eightfold) (all Western blots), and the gelatinolytic
      activity (zymography) of MMP-2 (twofold); it did not affect TIMP-1 and TIMP-2.
      FFA augmented the insulin-mediated increases in MMP-2 (from approximately six- to
      approximately 11-fold), MMP-9 (from approximately 13- to approximately 23-fold),
      MT1-MMP (from approximately eight- to approximately 20-fold), and MMP-2
      gelatinolytic activity (from two- to threefold). FFA also increased JNK and p38
      mitogen-activated protein kinase activities. The insulin- and FFA-induced
      hyperactivity of three proatherogenic MMPs in vascular tissues may promote
      degradation of extracellular matrix over time, leading to thinning of
      atherosclerotic capsules and acute vascular problems.

PMID- 18625124
TI  - The complexities of diabetic cardiomyopathy: lessons from patients and animal
      models.
AB  - Cardiovascular diseases are foreseeable complications of diabetes mellitus; heart
      failure is a prominent complication among these. Diabetic cardiomyopathy is a
      distinct entity independent of coronary artery disease and hypertension. Most of
      our knowledge on diabetic cardiomyopathy's pathogenesis comes from studies
      performed on various animal models. The recent advances in the domain confirm
      that the disease is above all a maladaptation of the heart mostly driven by the
      metabolic derangements that accompany diabetes mellitus.

PMID- 18625125
TI  - The genetic study of primary biliary cirrhosis: great hope, some caution.

PMID- 18625126
TI  - Otolaryngological perspective on patients with throat symptoms and laryngeal
      irritation.
AB  - The diagnosis of laryngopharyngeal reflux (LPR) is increasingly common in
      otolaryngology practice. Patients with nonspecific throat and voice symptoms,
      such as throat clearing, hoarseness, cough, sore throat, and globus, are
      frequently treated empirically with antireflux medication by otolaryngologists
      and primary care physicians. Physical findings such as laryngeal erythema, edema,
      and posterior laryngeal mucosal thickening are also frequently attributed to LPR.
      The literature has been inconsistent, with few prospective, randomized trials
      showing efficacy for this clinical practice. Because of the lack of specific
      signs and symptoms of LPR, clinicians should be aware of other potential causes
      for these clinical presentations. Recently published studies describe the
      association between allergy or asthma and many of the same symptoms attributed to
      reflux disease. Muscle tension dysphonia can also present with hoarseness and
      symptoms of throat irritation. Although LPR can cause the symptoms and signs
      described previously, it should not be the only diagnosis considered by the
      evaluating physician. Failure to consider other possible causes may result in
      unnecessary treatment and potential delay in diagnosis. This article discusses
      this topic, citing some of the pertinent literature published over the past 2
      years.

PMID- 18625127
TI  - Nonerosive reflux disease: a pathophysiologic perspective.
AB  - Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal
      reflux disease. By definition, patients with NERD have typical reflux symptoms
      caused by the intraesophageal reflux of gastric contents but have no visible
      esophageal mucosal injury. This is in contrast to patients with reflux
      esophagitis, also known as erosive reflux disease, and Barrett's esophagus, who
      have obvious esophageal mucosal injury on endoscopy. Only 50% of patients with
      NERD have pathologic esophageal acid contact time (ACT) as detected on 24-hour pH
      monitoring (ie, NERD-positive). NERD patients with physiologic esophageal ACT and
      good temporal correlation of symptoms with reflux events (symptom index > 50% or
      symptom-association probability > 95%) are considered to have esophageal
      hypersensitivity (ie, NERD-negative). Finally, patients with physiologic
      esophageal ACT but poor symptom-reflux correlation are now considered to have
      functional heartburn and not NERD. NERD-positive patients have motor dysfunction
      and acidic reflux abnormalities that are similar to patients with reflux
      esophagitis and Barrett's esophagus, whereas NERD-negative patients have minimal
      abnormalities that are not much different than healthy controls. The
      histopathologic feature most indicative of NERD is the presence of dilated
      intercellular spaces within squamous epithelium, an ultrastructural abnormality
      readily identified on transmission electron microscopy and on light microscopy.

PMID- 18625128
TI  - Potential adverse effects of proton pump inhibitors.
AB  - Proton pump inhibitors (PPIs) have revolutionized the management of
      gastroesophageal reflux disease and peptic ulcer disease over the past two
      decades. Among the most commonly prescribed agents worldwide, PPIs' overall
      safety profile is unquestionable. However, emerging evidence indicates that PPI
      therapy, particularly with long-term and/or high-dose administration, is
      associated with several potential adverse effects, including enteric infections
      (eg, Clostridium difficile), community-acquired pneumonia, and hip fracture, all
      of which have received much attention recently. We review the current data on
      these and other potential consequences of PPI therapy. More judicious use of PPIs
      (eg, administering them in no more than the minimum effective dose to older adult
      patients) may help to further limit the impact of some of these possible adverse
      effects.

PMID- 18625129
TI  - Endoscopic therapy for GERD: does it have a future?
AB  - Approximately 20% of patients with gastroesophageal reflux disease (GERD) have
      symptoms refractory to long-term proton pump inhibitor (PPI) therapy.
      Furthermore, PPI therapy is expensive. Fundoplication is considered the gold
      standard of GERD therapy in terms of normalization of esophageal acid exposure
      and symptom control; however, this exposes the patient to the risks of surgery
      and anesthesia. Therefore, an endoscopic approach to treating GERD that obviates
      the need for PPIs and avoids surgical morbidity is desirable. Several endoscopic
      methods have been used, including radiofrequency ablation, implantation of
      foreign substances as bulking agents, and various tissue apposition strategies.
      The emerging field of GERD endotherapy is promising, but more rigorous, sham
      controlled, long-term studies are required to elucidate its exact role in
      clinical practice. This review discusses the evolution of these concepts,
      describes specific endoscopic devices that have been developed, and explores the
      future of endotherapies as viable treatment alternatives for GERD.

PMID- 18625130
TI  - New esophageal function testing (impedance, Bravo pH monitoring, and high
      resolution manometry): clinical relevance.
AB  - Esophageal testing aims to quantify gastroesophageal reflux or characterize
      esophageal motility. Reflux monitoring traditionally has been based on the
      detection of acidic reflux by a transnasal catheter that measures esophageal pH.
      Recently there have been two major developments in this field: the wireless Bravo
      pH capsule (Medtronic, Inc., Minneapolis, MN), which allows catheter-free
      monitoring, and impedance-pH measurement, a catheter-based technique that enables
      detection of acidic and nonacidic reflux. The assessment of esophageal motility
      has relied on conventional manometry for many years. Two new procedures also
      recently became available to assess esophageal motility: high-resolution
      manometry, which uses many closely spaced pressure sensors and provides
      spatiotemporal plots of esophageal pressure changes, and impedance manometry, a
      test that directly measures bolus transit and provides conventional manometric
      data. The advantages, disadvantages, and clinical importance of these new
      esophageal tests are discussed in this review.

PMID- 18625131
TI  - The value of esophageal histology in the diagnosis of gastroesophageal reflux
      disease in patients with heartburn and normal endoscopy.
AB  - Histologic markers of reflux-induced mucosal injury are demonstrable in patients
      with nonerosive gastroesophageal reflux disease (neGERD). They include papillary
      elongation, basal cell hyperplasia, and dilation of intercellular spaces,
      especially of the prickle layer. These abnormalities are responsive to acid
      suppressive therapy. Unfortunately, the longitudinal and circumferential
      distributions of these anomalies are nonuniform. They are presumably focalized on
      top of the esophageal folds, where the brunt of acid exposure and injury occurs.
      Therefore, based on current evidence, routine, random, nontargeted biopsies of
      the distal esophagus cannot be recommended in patients with neGERD. This may
      change if future studies reveal a high sensitivity and specificity of biopsies
      obtained from the squamocolumnar junction and the tops of the mucosal folds at 2
      cm and 4 to 5 cm in patients with neGERD.

PMID- 18625132
TI  - Reflux cough.
AB  - Cough can be an extraesophageal manifestation of gastroesophageal reflux disease.
      This article summarizes recent progress in our understanding of the
      pathophysiology, diagnosis, and treatment of the reflux cough syndrome. Recent
      studies have provided further evidence for a role of weakly acidic
      gastroesophageal reflux in inducing cough. It has also been established that
      although reflux may induce cough, cough may also trigger reflux in some patients,
      and distinguishing between the two requires objective detection of cough burst
      (ie, by esophageal manometry). Treatment of the reflux cough syndrome is an issue
      of ongoing controversy and further studies.

PMID- 18625133
TI  - Management of high-grade dysplasia.
AB  - High-grade dysplasia is the last stage before the development of adenocarcinoma.
      Despite the fact that the lesion is not yet invasive, it has tremendous potential
      to become malignant. The approach to the disease has clinicians divided between
      immediate intervention with surgical resection or continued endoscopic
      surveillance proof of the unclear natural history. Much knowledge has been
      acquired recently regarding application of surveillance and outcomes of
      esophageal resection. Also, many endoscopic techniques for treating high-grade
      dysplasia have been studied in depth. Results on their safety, efficacy, and
      complication rates have recently become available. This review analyzes the
      progress in the understanding and treatment of high-grade dysplasia during the
      past 24 to 36 months and examines how this new information plays a role in the
      disease's treatment algorithm.

PMID- 18625134
TI  - Biomechanics of the esophagogastric junction in gastroesophageal reflux disease.
AB  - Gastroesophageal reflux is inherently mechanical in nature, driven by the
      pressure difference between the stomach and the esophagus in the setting of a
      relaxed or hypotensive sphincter. Recent advances in our understanding of
      esophagogastric junction (EGJ) biomechanics in the etiology of gastroesophageal
      reflux disease are highlighted here. We focus this review on three critical
      areas: the anatomy and physiology of the EGJ that predispose the junction to
      reflux, the mechanical compliance of the EGJ musculature that has significant
      pathophysiologic underpinnings, and the trans-sphincteric pressure gradients
      during gastroesophageal reflux. We also examine the mechanistic basis of a higher
      incidence of reflux in obese patients and conclude with some observations on the
      future of understanding EGJ biomechanics.

PMID- 18625135
TI  - Refractory GERD: what is it?
AB  - Refractory gastroesophageal reflux disease (GERD) is very common and may affect
      up to 40% of patients who use a proton pump inhibitor (PPI) once daily.
      Refractory GERD can present as incomplete or lack of response to PPI therapy. The
      disorder is clearly driven by patients, who present with a wide range of symptom
      severity and frequency while on PPI treatment. Poor compliance and improper
      timing of PPI consumption should always be excluded before further evaluation of
      this patient population. The putative mechanisms for refractory GERD include
      weakly acidic reflux, duodenogastroesophageal/bile reflux, visceral
      hypersensitivity, delayed gastric emptying, psychological comorbidity, and
      concomitant functional bowel disorders. Reduced PPI bioavailability, rapid PPI
      metabolism, PPI resistance, nocturnal reflux, and Helicobacter pylori infection
      status have very limited roles in refractory GERD. The contribution of
      eosinophilic esophagitis to refractory GERD is still unknown. Pill-induced
      esophagitis, Zollinger-Ellison syndrome, achalasia, and other disorders are
      rarely responsible for PPI failure and usually are not confused with GERD.

PMID- 18625136
TI  - Analysis of 24-hour esophageal pH monitoring: the effect of state of
      consciousness.
AB  - This review addresses current advances in the diagnosis of sleep-related
      gastroesophageal reflux using ambulatory esophageal pH monitoring and laboratory
      monitoring, which includes polygraphic assessment of the state of consciousness.
      This 24-hour pH monitoring uses a new strategy of interpretation that
      characterizes acidic reflux events and specifically assesses the patient's
      position and state of consciousness. Thus, the recognition of reflux events
      during waking and sleep will add to the overall assessment of gastroesophageal
      reflux and its severity and clinical relevance. The pH testing, together with
      overnight polysomnography, offers an opportunity to link nighttime reflux with
      disease severity. The application of multichannel impedance with pH monitoring
      allows detection of acidic and nonacidic reflux events during sleep and also
      helps to elucidate the physiologic response of the esophagus to these events
      during sleep. The significance of these findings will increase our knowledge of
      esophageal physiology and the pathologic mechanisms underlying gastroesophageal
      reflux disease.

PMID- 18625137
TI  - Reflux monitoring: current status.
AB  - Gastroesophageal reflux monitoring is a key investigation in managing
      gastroesophageal reflux disease. Esophageal pH monitoring is used to quantify
      esophageal acid exposure and the association of symptoms with acidic reflux
      episodes. Recently available wireless pH monitoring systems allow reflux
      monitoring over prolonged periods and increase patient comfort during the
      procedure. Combined impedance-pH monitoring offers the ability to identify reflux
      episodes independently of their acid content, an important advantage when
      evaluating patients with symptoms persisting during acid-suppressive therapy.

PMID- 18625138
TI  - Laryngeal manifestations of gastroesophageal reflux disease.
AB  - Chronic laryngeal signs and symptoms associated with gastroesophageal reflux
      disease (GERD) are often referred to as reflux laryngitis or laryngopharyngeal
      reflux (LPR). It is estimated that up to 15% of all visits to otolaryngology
      offices are because of manifestations of LPR. Damage to laryngeal mucosa may be
      the result of reflux of gastroduodenal contents, whether chronic or a single
      incident. The most common presenting symptoms of LPR include hoarseness, sore
      throat, throat clearing, and chronic cough. The diagnosis of LPR is usually made
      on the basis of presenting symptoms and associated laryngeal signs, including
      laryngeal edema and erythema. The current recommendation for managing these
      patients is empiric therapy with twice-daily proton pump inhibitors for 1 to 2
      months. Other causes of laryngeal irritation are considered in most of those who
      are unresponsive to such therapy. Surgical fundoplication is most effective in
      those who are responsive to acid-suppressive therapy.

PMID- 18625139
TI  - Laryngopharyngeal reflux: the value of otolaryngology examination.
AB  - Laryngopharyngeal reflux (LPR) is the disease process by which gastric contents
      affect the extraesophageal structures of the head and neck. The symptoms of LPR
      include intermittent dysphonia, excessive throat clearing, globus pharyngeus,
      cough, and dysphagia. These symptoms can be assessed with the Reflux Symptom
      Index. Signs of LPR, as determined with laryngoscopy, can be described with the
      Reflux Findings Score, which includes assessment of site-specific laryngeal edema
      and other inflammatory changes. This article discusses the current understanding
      of LPR pathophysiology, taking into account pepsin stability and reactivation.

PMID- 18625140
TI  - Diagnostic options for patients with refractory GERD.
AB  - Patients with refractory gastroesophageal reflux disease (GERD) are those who
      have persistent symptoms while being treated with proton pump inhibitors (PPIs).
      One third of GERD patients requiring a daily PPI are estimated to eventually
      experience treatment failure. These patients are usually referred for further
      investigation to confirm the presence of GERD or to identify other entities as
      the cause of symptoms. Tools that can be used in this diagnostic process include
      upper gastrointestinal endoscopy with analysis of esophageal biopsies, esophageal
      pH monitoring, impedance-pH monitoring, and esophageal bilirubin monitoring. The
      conventional diagnostic approach includes upper gastrointestinal endoscopy and
      ambulatory pH monitoring while receiving PPI therapy. New diagnostic techniques
      that may be useful with refractory GERD include impedance-pH monitoring, which is
      very sensitive in detecting persistent weakly acidic reflux, and bilirubin
      monitoring, which detects increased esophageal exposure to bile. Gastric pH
      monitoring should be reserved for patients in whom PPI resistance is suspected.

PMID- 18625141
TI  - Factors influencing functional abdominal pain in children.
AB  - Functional gastrointestinal disorders (FGIDs) commonly affect children and are
      associated with short- and long-term morbidity. Although the pathogenesis of pain
      related FGIDs remains incompletely understood, most investigators agree on a
      multifactorial etiology and the presence of an altered brain-gut interaction. A
      continuous interplay of genetic and environmental factors appears to shape the
      development of the central and enteric nervous systems. The biopsychosocial model
      is the current operational framework for children with FGIDs, as it recognizes
      the interaction between social and environmental influences and psychological and
      physiologic processes. The biopsychosocial model proposes that specific
      permutations of genetic susceptibility, early life experiences, sociocultural
      issues, and coping mechanisms could explain the variability in clinical
      presentation and outcome among individuals.

PMID- 18625142
TI  - Alternative strategies for the use of infliximab in pediatric inflammatory bowel
      disease.
AB  - Infliximab is approved for the induction and 1-year maintenance of remission in
      pediatric Crohn's disease unresponsive to conventional therapy. Despite
      significant experience with the use of this agent in children and adolescents who
      have inflammatory bowel disease, many questions about its optimal use remain.
      Recent safety concerns raised debate over the common practice of using infliximab
      in combination with conventional immunomodulatory agents. Additionally, although
      regularly scheduled administration maintains remission more effectively than
      episodic therapy, it is not known whether all patients who start infliximab must
      continue it for maintenance. Some patients may be able to use infliximab for
      induction and another agent for maintenance. Finally, the optimal placement of
      infliximab in the algorithm for the medical treatment of pediatric inflammatory
      bowel disease remains an open question.

PMID- 18625143
TI  - Nutrition and nonalcoholic fatty liver disease in children.
AB  - Nonalcoholic fatty liver disease (NAFLD) is an obesity-associated liver disease
      found in 3% to 9% of children in the United States. NAFLD represents a spectrum
      of liver disease and is frequently associated with features of the metabolic
      syndrome. Nutrition's role in NAFLD is complex. It does not appear that
      overweight children with NAFLD have an unusual diet compared with their
      overweight counterparts without NAFLD. It is more likely that they have increased
      genetic susceptibility to the general poor diet and state of positive calorie
      balance currently found in many children. The available treatment studies using
      nutrition counseling and increased physical activity are promising. We recommend
      initiating sustainable family-oriented lifestyle changes in all children with
      NAFLD.

PMID- 18625144
TI  - Patterns of gastrointestinal disease associated with mutations of CFTR.
AB  - This review focuses on the pathobiology of the gastrointestinal and hepatic
      manifestations of cystic fibrosis (CF) disease in relation to their genetic basis
      in mutations of the CF transmembrane conductance regulator (CFTR) gene. It
      reviews the nature of the CFTR protein, a categorization of the types of gene
      mutations underlying CF's various manifestations, and the ways in which absent or
      reduced CFTR produces various functional abnormalities in the different organs
      affected by CF. Subsequently, the particular organ-related clinical
      manifestations of CF directly associated with loss of CFTR function are
      addressed. Thereafter, the review discusses some of the complexities of the
      genotype-phenotype relationships related to milder mutations or complex genetic
      disorders in which CFTR abnormalities interact with other genetic and
      environmental factors, and the potential diagnostic roles of sweat testing or
      other electrophysiologic testing. This discussion examines secondary
      gastrointestinal manifestations of CF and the particular cases of diseases that
      may be related to abnormalities of CFTR.

PMID- 18625146
TI  - Biliary dyskinesia in the pediatric patient.
AB  - The term biliary dyskinesia commonly describes a motility disorder of the biliary
      tract that is divided into two main categories: gallbladder dyskinesia (GBD) and
      sphincter of Oddi dysfunction (SOD). SOD is further subdivided into biliary SOD
      and pancreatic SOD. GBD causes typical biliary colic without gallstones, whereas
      SOD typically presents with recurrent pancreatitis or chronic abdominal pain,
      usually after cholecystectomy. GBD and SOD are uncommon in children. Based on
      adult experience, this review discusses the diagnosis and treatment of GBD and
      SOD in the pediatric population.

PMID- 18625145
TI  - Step-up and step-down approaches to treatment of gastroesophageal reflux disease
      in children.
AB  - The single biggest change in the approach to treating pediatric gastroesophageal
      reflux disease (GERD) in recent years has been the empiric use of proton pump
      inhibitors (PPIs) for symptoms suspected to be those of GERD. In other words,
      PPIs have been used increasingly as a first-line concurrent diagnostic test and
      treatment before any investigation. Although this approach is useful for some
      patients, there are a number of caveats about its application to children. In
      general, these caveats are related to age per se (eg, infancy) and to age-related
      symptoms and severity of GERD itself. The most important caveats relate to the
      prescription of empiric PPI therapy in infants--which generally is to be avoided-
      and to how PPIs are used in older children--specifically, the advisability of
      empiric trials being of limited duration. Even in children with proven reflux
      esophagitis, GERD is not chronic and relapsing in all; thus, trials of therapy
      withdrawal are warranted. In light of many factors, including the burgeoning
      literature on potential risks of infections in acid-suppressed children and
      adults, caution with dose and duration of acid-suppressive drugs in children is
      urged. The role of antireflux surgery is also mentioned.

PMID- 18625147
TI  - Acute mesenteric ischemia.
AB  - Acute mesenteric ischemia is caused by a critical reduction in intestinal blood
      flow that frequently results in bowel necrosis and is associated with a high
      mortality. Clinicians must maintain a high index of suspicion because a prompt
      diagnosis and early aggressive treatment before the onset of bowel infarction
      results in reduced mortality. Medical management includes aggressive rehydration
      and the use of antibiotics, anticoagulation, vasodilators, and inhibitors of
      reperfusion injury. If acute mesenteric ischemia is suspected, early angiography
      is imperative, as it permits accurate diagnosis and possible therapeutic
      intervention. Therapeutic options during angiography depend on the cause of
      ischemia and include administering intra-arterial vasodilators and/or
      thrombolytic agents and angioplasty with or without stent placement. If
      interventional techniques are not possible or if the patient presents with
      suspicion of bowel infarction, surgery is warranted. Surgical techniques include
      superior mesenteric artery embolectomy or visceral artery bypass, which should be
      used before bowel resection to ensure only resection of nonviable bowel.

PMID- 18625148
TI  - Omeprazole in infants 3 to 12 months old.

PMID- 18625149
TI  - Omeprazole in preterm infants.

PMID- 18625150
TI  - Esomeprazole in infants 1 to 24 months old.

PMID- 18625152
TI  - ADVANCE in management of vascular complications of diabetes.

PMID- 18625151
TI  - Insulin resistance, microalbuminuria, and chronic kidney disease.

PMID- 18625153
TI  - A new mandate for treating hypertension in the elderly.

PMID- 18625154
TI  - Evidence for benefits of angiotensin receptor blockade beyond blood pressure
      control.
AB  - Elevated levels of angiotensin II result in oxidative stress and endothelial
      dysfunction, which initiate atherogenic pathologic processes that are important
      in cardiovascular disease development. Angiotensin II induces its deleterious
      effects primarily through the type 1 receptor; these effects are inhibited by
      angiotensin II receptor blockers (ARBs) directly at the receptor level.
      Angiotensin II may potentiate protective mechanisms through stimulation of the
      type 2 receptor, which is not blocked by ARBs. Accumulating data suggest that
      blockade of angiotensin II production or activity provides vascular and
      cardioprotective benefits, such as reduction of atrial fibrillation, acute
      myocardial infarction, and heart failure events. Moreover, blockade of the renin
      angiotensin system has been shown to offer renal protection in subjects with and
      without diabetes mellitus and to reduce the risk of new-onset diabetes.

PMID- 18625155
TI  - Dopamine receptors and hypertension.
AB  - Dopamine plays an important role in regulating renal function and blood pressure.
      Dopamine synthesis and dopamine receptor subtypes have been shown in the kidney.
      Dopamine acts via cell surface receptors coupled to G proteins; the receptors are
      classified via pharmacologic and molecular cloning studies into two families, D1
      like and D2-like. Two D1-like receptors cloned in mammals, the D1 and D5
      receptors (D1A and D1B in rodents), are linked to adenylyl cyclase stimulation.
      Three D2-like receptors (D2, D3, and D4) have been cloned and are linked mainly
      to adenylyl cyclase inhibition. Activation of D1-like receptors on the proximal
      tubules inhibits tubular sodium reabsorption by inhibiting Na/H-exchanger and
      Na/K-adenosine triphosphatase activity. Reports exist of defective renal dopamine
      production and/or dopamine receptor function in human primary hypertension and in
      genetic models of animal hypertension. In humans with essential hypertension,
      renal dopamine production in response to sodium loading is often impaired and may
      contribute to hypertension. A primary defect in D1-like receptors and an altered
      signaling system in proximal tubules may reduce dopamine-mediated effects on
      renal sodium excretion. The molecular basis for dopamine receptor dysfunction in
      hypertension is being investigated, and may involve an abnormal posttranslational
      modification of the dopamine receptor.

PMID- 18625156
TI  - Race-based therapeutics.
AB  - The issue of race in medicine is problematic. Race is not a physiologic grouping,
      and all persons of a given race do not necessarily share the same clinical
      phenotype or genetic substrate. Despite clear signals that certain risk factors
      and diseases vary as a function of race, translating those differences into race
      based therapeutics has been awkward and has done little to change the natural
      history of cardiovascular disease as it affects special populations. Among the
      varied special populations, the African American population appears to have the
      most significant and adverse variances for cardiovascular disease as well as
      worrisome signals that drug responsiveness varies. Recent guideline statements
      have now acknowledged certain treatment options that are most appropriate for
      African Americans with cardiovascular disease, especially hypertension and heart
      failure. As more physiologic markers of disease and drug responsiveness become
      available, the need for racial designations in medicine may lessen, and therapies
      can be optimized for all patients without regard to race or ethnicity.

PMID- 18625157
TI  - Do ACE inhibitors all provide the same outcomes benefits in high-risk
      cardiovascular patients?
AB  - The Heart Outcomes Prevention (HOPE) trial was the first to demonstrate the
      benefits of the angiotensin-converting enzyme (ACE) inhibitor ramipril for high
      risk cardiovascular patients. Whether the cardioprotective effects seen in HOPE
      and other trials are specific to distinct ACE inhibitors remains controversial.
      Evidence of a lack of class effect for ACE inhibitors has policy and financial
      implications related to reference pricing by insurers and inclusion on pharmacy
      formularies. Because head-to-head trials comparing the different ACE inhibitors
      are unforeseen, clinicians and administrators must rely on secondary-level data
      and observational studies. Only a handful of studies have sought to address the
      dispute over a class effect among ACE inhibitors, which is reviewed in this
      article.

PMID- 18625158
TI  - Should chlorthalidone be the diuretic of choice for antihypertensive therapy?
AB  - For decades, diuretic therapy has been a cornerstone in treating hypertension, an
      approach supported by multiple randomized controlled trials demonstrating reduced
      morbidity and mortality from cardiovascular events. Yet controversy persists
      regarding the potential detrimental metabolic effects and side effects of
      diuretic agents. Within the risk-benefit debates about diuretic therapy is a
      second dialogue regarding the best thiazide or thiazidelike agent to prescribe.
      Proponents of chlorthalidone emphasize the demonstrated reductions in
      cardiovascular events reported from multiple classic trials and its longer half
      life, whereas opponents point to its limited availability in low-dose forms and
      comparable favorable results from hydrochlorothiazide-based therapy to discredit
      claims of superiority. This review presents the data available on both sides of
      this issue to help the reader decide which claims are most valid, and offers
      recommendations for treatment.

PMID- 18625159
TI  - Treating very elderly hypertensive patients is rewarding: the HYVET results.

PMID- 18625160
TI  - ONTARGET for hypertension or not?

PMID- 18625161
TI  - Advances in the understanding of eclampsia.
AB  - Preeclampsia, a serious hypertensive complication of pregnancy characterized by
      new-onset hypertension and proteinuria after midpregnancy, is a multisystem
      disorder that often involves the central nervous system. Neurologic signs and
      symptoms include hyperreflexia, headaches, visual disturbance, seizures, and
      cerebral hemorrhage. Eclampsia-new-onset seizures in the setting of preeclampsia
      usually occurs before or within 48 hours of delivery, but can present as late as
      1 month postpartum (late postpartum eclampsia). Magnesium sulfate is the drug of
      choice to prevent and treat eclampsia, a recommendation validated through large,
      randomized, and placebo-controlled trials. This review describes the
      pathogenesis, clinical features, and treatment of eclampsia, focusing on recent
      observations regarding roles of circulating antiangiogenic factors in the
      pathogenesis of the neurologic complications of eclampsia.

PMID- 18625162
TI  - Direct renin inhibition: an analysis of possible benefits.
AB  - The US Food and Drug Administration's approval in March 2007 of aliskiren, the
      first commercially available direct renin inhibitor, for the treatment of
      hypertension met with great enthusiasm. Clinical trials have demonstrated it to
      be as effective as other commonly prescribed antihypertensive agents with few
      side effects. Preclinical studies in genetically manipulated rats have shown it
      to be effective in reversing angiotensin II-induced cardiac and renal damage.
      Despite the notable absence of human clinical data for this agent, many
      clinicians have touted aliskiren as the ideal agent to achieve additional
      suppression of the renin-angiotensin-aldosterone system (RAAS) as a means to
      reduce the morbidity and mortality of chronic diseases of the cardiovascular and
      renal systems. Clinical studies are ongoing and future studies are planned to
      prove its effectiveness in several chronic diseases known to be related to RAAS
      activation.

PMID- 18625163
TI  - Insulin resistance and blood pressure.
AB  - Insulin resistance, cardiometabolic syndrome, and hypertension are common health
      problems with significant consequences for individuals and society. The
      pathogenesis of these disorders is complex and not fully understood. In this
      article we review the current knowledge about the effects of lifestyle
      modification and pharmacologic antihypertensive agents on insulin resistance and
      hypertension.

PMID- 18625164
TI  - Treating prehypertension: a review of the evidence.
AB  - Although the term "prehypertension" has been challenged by some, its use to
      define people with systolic blood pressure (BP) between 120 and 139 mm Hg and/or
      diastolic pressures between 80 and 89 mm Hg has gained general acceptance. The
      category includes as many people as the number who have hypertension, defined as
      blood pressure of 140/90 or above. Such people are clearly at an increased risk
      of cardiovascular damage compared with people with BPs below 120/80 mm Hg. The
      major unresolved issue is the appropriate management of such patients. Two trials
      have attempted to document the value of short-term drug therapy to prevent the
      progression of BP to overt hypertension, but no outcome studies are currently
      available.

PMID- 18625165
TI  - Pharmacologic considerations in the positioning of beta-blockers in
      antihypertensive therapy.
AB  - Beta-blockers have been used to treat hypertension for decades, either as
      monotherapy or combined with other antihypertensive agents, primarily diuretics,
      often as fixed-dose combination products. Although beta-blockers can lower blood
      pressure in most patients, outcomes data with these drugs have been disappointing
      and their value for patients without "compelling indications" has been questioned
      recently. The early beta-blockers had significant pharmacologic shortcomings;
      however, later-generation beta-blockers have distinctive and presumably better
      pharmacologic profiles. The most recently introduced drugs, the vasodilating beta
      blockers carvedilol and nebivolol, are now being broadly evaluated as to their
      efficacy and tolerability in clinical practice.

PMID- 18625166
TI  - Colorectal cancer screening: how to help patients comply.
AB  - PURPOSE: We elicited patient opinions about how physicians can improve
      communications about colorectal cancer (CRC) screening. METHODS: We recruited 15
      patients, ages 50 years and older, from an urban family medicine teaching clinic.
      All patients in the initial pool of candidates had been seen at the university of
      Arkansas for Medical Sciences Family Medical Center within the past 12 months.
      The recruits participated in 1 of 3 focus groups to discuss how to enhance the
      rate of CRC screening. Participants watched a videotape that described the
      different approaches to CRC screening. We then asked them to comment on how
      patients could be encouraged to undergo CRC screening. RESULTS: using a
      qualitative analysis of focus group data, we determined the most common reasons
      participants had not undergone CRC screening: fear, lack of information, and
      failure of the physician to strongly recommend CRC screening. Participants
      offered 7 recommendations for how physicians could address their concerns.
      Participants emphasized the importance of strong physician endorsement of
      screening, of frank and informative dialogue about patient's concerns, and of
      using educational materials to supplement personal advice. CONCLUSION: A
      physician's recommendation for screening is the most powerful motivator in
      patients' decisions. However, other sources of information such as videotapes,
      written materials, and even endorsement of CRC screening by the clinic's office
      staff can help patients decide to undergo screening.

PMID- 18625167
TI  - Statins and elevated liver tests: what's the fuss?
AB  - Order liver function tests before starting statin therapy, 12 weeks after
      initiation, with any dose increase, and periodically for long-term maintenance
      therapy. Mild elevations of alanine aminotransferase (ALT) or aspartate
      aminotransferase (AST) (<3 times the upper limit of normal [ULN]) following
      statin therapy do not appear to lead to significant liver toxicity over time.
      Other medications that lower low-density lipoprotein (LDL), and might be
      substituted for statins, may not improve morbidity and mortality.

PMID- 18625168
TI  - Benign prostatic hyperplasia: treat or wait?
AB  - Talk to every male patient over the age of 50 about urinary function. Utilize
      questionnaires, such as the International Prostate Symptom Score to evaluate the
      patient's perception of symptom severity and quality of life. Rule out potential
      causes of lower urinary tract symptoms with a thorough medical history, focused
      physical exam (including digital rectal examination and neurological
      assessments), and appropriate laboratory evaluations. When choosing treatment for
      benign prostatic hyperplasia, remember that quality of life is generally more
      important than symptom severity.

PMID- 18625169
TI  - Patients insist on antibiotics for sinusitis? Here is a good reason to say "no".
AB  - Stop prescribing antibiotics for adults with a clinical diagnosis of acute
      sinusitis, unless the patient has severe symptoms. Antibiotics have little if any
      positive effects on the severity and duration of symptoms, and they cause adverse
      effects and create unnecessary expense.

PMID- 18625170
TI  - Should you screen--or not? The latest recommendations.
AB  - Last year, and in the early part of this year, the Task Force issued a number of
      recommendations on topics ranging from hypertension screening to screening for
      illicit drug use. While some of these recommendations were reaffirmations of past
      recommendations, others included some changes. The Task Force has: 1) dropped the
      age for routine screening for Chlamydia in sexually active women from 25 years
      and younger to 24 and younger; 2) added a recommendation against the use of
      aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent
      colorectal cancer (CRC); 3) changed its recommendation on screening for carotid
      artery stenosis. In 1996, the Task Force noted that the evidence was insufficient
      to make a recommendation; in 2007 it recommended against such routine screening;
      4) added recommendations on counseling patients about drinking and driving, as
      well as on screening for illicit drug use. In both cases, the Task Force says the
      evidence is insufficient to recommend for or against.

PMID- 18625171
TI  - Tender growth on toe.
AB  - A 50-year-old Caucasian man came to the dermatology clinic with a tender growth
      on his great toe. He first noticed it a year earlier after sustaining trauma to
      the area. The growth had been getting bigger and had intermittently bled. It had
      also oozed, so his primary care physician treated it as an infection with topical
      antibiotics, followed by several courses of oral antibiotics. Despite therapy,
      the lesion continued to grow and the patient was referred to us. The patient had
      a 3.4-cm-by-1.8-cm exophytic erythematous nodule on the left lateral great toe.
      What is your diagnosis? How would you manage this condition?

PMID- 18625172
TI  - Does regular exercise reduce the pain and stiffness of osteoarthritis?
AB  - Exercise helps reduce the pain, but it's unclear whether it helps with stiffness.
      Exercise moderately reduces pain in elderly patients with osteoarthritis and has
      a small effect on reducing self-reported disability. No studies have evaluated
      the effect of exercise on stiffness.

PMID- 18625173
TI  - Clinical inquiries. What are the most effective ways you can help patients stop
      smoking?

PMID- 18625174
TI  - Clinical inquiries. Does antepartum perineal massage reduce intrapartum
      lacerations?

PMID- 18625175
TI  - Clinical inquiries. What is the best way to screen for breast cancer in women
      with implants?

PMID- 18625177
TI  - [Empiric use of antibiotics in nosocomial infections].

PMID- 18625176
TI  - Clinical inquiries. What is the best treatment for oral thrush in healthy
      infants?

PMID- 18625178
TI  - [Perception of clinical practice derived risks compared to adverse effects
      detected in an internal medicine service].
AB  - BACKGROUND AND OBJECTIVE: To know how the health care workers perceive the risks
      derived from the care practice. To estimate the most frequent adverse effects
      (AE) and establish differences and similarities between the perception of risks
      and the AE produced. MATERIAL AND METHOD: A self-administered questionnaire was
      applied to all the workers of an Internal Medicine Department of a General
      University Hospital on perception of risks and safety of the patient. After, and
      by using the screening guide of the IDEA project, edition 1, the clinical
      histories of the patients selected were analyzed by medical residents of
      preventive Medicine and Internal Medicine. RESULTS: Questionnaire. Fifty
      questionnaires we sent with a 42% response rate. Risks prioritized by obtaining a
      lower mean score: there is not action plan against catastrophes (2.79/10) and
      lack of spaces to report (3/10); those having greater percentage of open
      questions: long maintenance of urinary probes (47.61%) and inadequate
      prescription of antibiotics (33.33%). Study of AE. Incidence of patients with AE:
      25% (95% CI 11.06-38.9). Incidence of AE: 26.6% (95% CI 12.6-40.6). 41.6% of AE
      was related to medication, 25% to nosocomial infection, 16.66% to technical
      problems in procedures and 16.66% were related to nursing cares. CONCLUSIONS: The
      perception of the health care workers on health care practice derived risks is
      different from the adverse events that really appear. The professionals are
      concerned about the information to patients than about scientific and technical
      quality. The most frequent adverse events produced are those related with
      medication. The only common point is concern for nosocomial infection.

PMID- 18625179
TI  - [Comparison of the definitions of the metabolic syndrome according to ATP III and
      IDF].
AB  - INTRODUCTION: The International Diabetes Federation (IDF) has recently proposed
      new criteria to define metabolic syndrome (MS). The aim of this study has been to
      determine the differences between these criteria and those of the classical
      National Cholesterol Education Program-Adult Program III (NCEP-ATP III). We have
      also aimed to determine whether our previous description of hepatic disorders in
      MS patients would be confirmed in a larger sample of patients and whether there
      were any differences between these and other variables when applying the two
      diagnostic criteria. MATERIAL AND METHODS: A sample of 866 patients from a
      cardiovascular risk unit was studied, recording biomedical and analytical
      variables. RESULTS AND DISCUSSION: Total prevalence of MS was similar for both
      definitions, however the SM identified population did not match in a significant
      percentage of patients (11%). There were also differences between genders: MS was
      more frequent in males using IDF criteria, but more frequent in females with ATP
      III criteria. The following was found when both types of criteria were related
      with the different quantitative variables analyzed: there was an increase in
      albuminuria (p = 0.038) in the ATP III MS patients while the IDF MS patients had
      a significant increase in ALT (p = 0.026) and ALT/AST ratio (p < 0.016).
      CONCLUSION: Further studies are needed to evaluate which of the two criteria are
      more useful for the prevention of future cardiovascular events.

PMID- 18625180
TI  - [Stroke in the hands of the internist. Cardiovascular risk factors].
AB  - INTRODUCTION: This study has aimed to describe cardiovascular risk factors (CVRF)
      associated to stroke and their detection and monitoring during the acute episode
      and the recommendations on hospital discharge. The hypothesis was to check if the
      integral care of the internist improved the care to these patients. MATERIAL AND
      METHODS: The clinical histories of patients who had suffered a stock between
      January 2002 and December 2003 were reviewed, obtaining different biological and
      clinical variables. RESULTS: We obtained a total of 727 patients suffering
      cerebral vascular disease (CVD). Of these, 194 (26.7%) patients were discharged
      from the Emergency Department and 533 required hospitalization. The most frequent
      etiology was atherothrombotic ischemia, except in patients under 45 years in
      which it was the undetermined. The most prevalent CVRF was arterial hypertension.
      CONCLUSIONS: Action on the CVRFs during admission and at the time of discharge
      was deficient. Secondary prevention programs of CVRF in stroke are required to
      improve care, quality of life and decrease relapse risk.

PMID- 18625181
TI  - [Spontaneous infectious spondylodiscitis in an internal medicine department:
      epidemiological and clinical study in 41 cases].
AB  - INTRODUCTION: The clinical-epidemiological characteristics of patients who were
      diagnosed of spontaneous infectious spondylodiscitis (SIS) in our Internal
      Medicine Department are analyzed and the related factors associated with the
      increase of the incidence are evaluated. PATIENTS AND METHODS: A cross-sectional,
      retrospective study of patients diagnosed of SIS from 1996 to 2005 was conducted.
      The study was divided in two periods: A (1996-2000) and B (2001-2005) and two
      main etiologic groups (pyogenic SIS and mycobacterial SIS) were compared.
      RESULTS: A total of 41 patients were diagnosed of SIS: 13 (31.7%) in period A and
      28 (68.3%) in period B. Mean age was 58.5 +/- 17.6 years (range: 29-89). There
      were 73.2% men and all women presented in period B (0 vs 11, p = 0.008).
      Backgrounds were: 28 (68.3%) predisposing factors for SIS, 22 (53.6%), previous
      infections and 23 (56.1%) spinal diseases. There were not changes in the
      backgrounds during the study. The etiology of SIS was: 26 (63.4%) pyogenic, 12
      (29.3%) mycobacterial and 3 (7.3%) brucellar. Patients with pyogenic SIS were
      older (63.6 +/- 3.2 vs 51.2 +/- 5.1 years, p = 0.035) and had less from onset of
      symptoms to diagnosis (62 +/- 12 vs 291 +/- 66 days, p = 0.0001) than patients
      with mycobacterial SIS. Total incidence of SIS and incidence of pyogenic SIS
      increased significantly during the study: (1.7/1000 admissions/year, p = 0.0057)
      and (1/1000 admissions/year, p = 0.0476). In the multivariate analysis, time from
      onset of symptoms to diagnosis was the only variable independently associated
      with the pyogenic etiological group (OR: 0.985, 95% CI: 0.975, 0.996, p = 0.005).
      CONCLUSIONS: In our study, the increasing incidence of SIS was related to an
      increase in pyogenic SIS incidence. Although older age and some backgrounds could
      be orientative of SIS etiology, these factors did not increase during the study.

PMID- 18625182
TI  - [Morbidity-mortality in nonagenarians with backgrounds of cerebral vascular
      accident or femur fracture. NonaSantfeliu Study].
AB  - OBJECTIVE: To evaluate in community-dwelling nonagenarians the influence of
      having previously suffered a stroke or a hip fracture. METHODS: 128 nonagenarians
      (mean age was 93.5 +/- 3.1 years) who were living in their own homes were
      evaluated prospectively. We evaluated total mortality and functional decline
      after two years of follow-up. RESULTS: Forty-eight patients (37.5%) died, and in
      29 (36.2%) of the 80 surviving patients there was a functional decline. In 77
      (60.2%) patient a bad clinical course was collected (death or functional
      decline). In the patients with prior stroke or hip fracture there was a worse
      overall clinical course (mortality or loss of functionality) than in the
      remaining patients (p = 0.03). CONCLUSIONS: Community-dwelling nonagenarians with
      a stroke or hip fracture history underwent a worse clinical course (mortality and
      functional decline) after two years of follow-up.

PMID- 18625183
TI  - [Non-pharmacological measures in the secondary prevention of atherothrombic
      stroke of the elderly. Current status of the subject].
AB  - Stroke represents a primary health problem in the elderly population. It is the
      first cause of mortality in women over 65 years, and that of men over 75 years in
      our country. Atheromatous carotid disease (ACD) is a fundamental etiological
      factor for the development of ischemic stroke. It is known that approximately 10%
      of the subjects with stroke have carotid stenosis of 50% or greater. Non
      pharmacological management of the ACD in elderly subjects is an increasingly more
      frequent clinical problem in the daily practice and a subject that is
      traditionally under debate. The aim of this article is to review the current
      status of knowledge on this controversial subject and to be able to apply it to
      our clinical practice.

PMID- 18625184
TI  - [Use of the propensity score methodology in health care research].
AB  - Observational studies are frequently used in biomedical research to determine
      associations between a treatment or exposure and the effects they can produce.
      Randomized control trials have been developed with the same purpose. Although
      they provide more precise results, they are more complex and costly. The use of
      propensity score methodology in observational studies helps to decrease the
      appearance of bias that they normally present, making them more accurate and with
      better reliability than randomized control trials. Given the increase in the use
      of the propensity score methodology in clinical research in recent years, we
      consider that it is of particular interest to make a description of it,
      highlighting its application scope and different use techniques.

PMID- 18625185
TI  - [Preventing dependency in the elderly].
AB  - INTRODUCTION: Dependency, i.e. the need to depend on another person to perform
      activities of daily living, is the main concern and cause of suffering and poor
      quality of life in the elderly. The prevalence of dependency increases with age
      and is related to the presence of prior disease and fragility. Dependency is
      associated with increased morbidity, mortality and institutionalization, as well
      as with greater health and social resource utilization, all of which increases
      health costs. OBJECTIVE: To create a consensus document on the main health
      recommendations for the prevention of dependency in the elderly, based on the
      scientific evidence available to date, with the collaboration of scientific
      societies and public health administrations (the Spanish Ministry of Health,
      Autonomous Communities and Cities). METHODS: a) a preliminary consensus document
      was drafted by an expert group composed of representatives of various scientific
      societies and health administrations. This document was based on a review of the
      recommendations and guidelines published by the main organizations involved in
      health promotion and the prevention of disease, functional deterioration and
      dependency in the elderly; b) the consensus document was reviewed by the
      remaining experts assigned by the scientific societies and central and autonomous
      administrations; c) the final document was approved after a session in which the
      text was discussed and reviewed by all the experts participating in the working
      group (including the academic committee); d) the document was presented and
      discussed in the First National Conference on Prevention and Health Promotion in
      Clinical Practice in Spain. All participating experts signed a conflicts of
      interest statement. RESULTS: The document provides recommendations, with their
      grades of evidence, grouped in the following three categories: a) health
      promotion and disease prevention, with specific preventive activities for the
      elderly, including prevention of geriatric syndromes; b) prevention of functional
      deterioration, with clinical recommendations that can be applied in primary and
      specialized care; c) prevention of iatrogeny (drug prescription, inappropriate
      use of diagnostic and therapeutic modalities and healthcare). These
      recommendations were tailored to the characteristics of the older person (OP),
      categorized in five groups: healthy OP, OP with chronic disease, fragile or at
      risk OP, dependent OP, and OP at the end of life. CONCLUSION: These
      recommendations should be implemented by public health administrations to improve
      strategies for the prevention of dependency in the elderly in the xxi century.

PMID- 18625186
TI  - [Fever and generalized pustular eruption].

PMID- 18625187
TI  - [Dry cough in a patient with systemic lupus erythematosus].

PMID- 18625188
TI  - [The key is in the clinical history].

PMID- 18625189
TI  - [Tumors in sternocleidomastoid muscle].

PMID- 18625190
TI  - [New indications of quinidine rescue it from the forgotten].

PMID- 18625191
TI  - [Murine typhus is a cause of fever of intermediate duration].

PMID- 18625192
TI  - [What do young internists choose in the entrance examinations?].

PMID- 18625193
TI  - [Charcot arthropathy and neuropathic plantar ulceration caused by hereditary
      sensory and autonomic neuropathy].

PMID- 18625194
TI  - [Spontaneous idiopathic thrombosis of the internal jugular vein].

PMID- 18625195
TI  - Purinergic (ATP) signaling stimulates JNK1 but not JNK2 MAPK in osteoblast-like
      cells: contribution of intracellular Ca2+ release, stress activated and L-voltage
      dependent calcium influx, PKC and Src kinases.
AB  - This work shows that ATP activates JNK1, but not JNK2, in rat osteoblasts and ROS
      A 17/2.8 osteoblast-like cells. In ROS-A 17/2.8 cells ATP induced JNK1
      phosphorylation in a dose- and time-dependent manner. JNK1 phosphorylation also
      increased after osteoblast stimulation with ATPgammaS and UTP, but not with
      ADPbetaS. RT-PCR studies supported the expression of P2Y(2) receptor subtype. ATP
      induced JNK1 activation was reduced by PI-PLC, IP(3) receptor, PKC and Src
      inhibitors and by gadolinium, nifedipine and verapamil or a Ca(2+)-free medium.
      ERK 1/2 or p38 MAPK inhibitors diminished JNK1 activation by ATP, suggesting a
      cross-talk between these pathways. ATP stimulated osteoblast-like cell
      proliferation consistent with the participation of P2Y(2) receptors. These
      results show that P2Y(2) receptor stimulation by ATP induces JNK1 phosphorylation
      in ROS-A 17/2.8 cells in a way dependent on PI-PLC/IP(3)/intracellular Ca(2+)
      release and Ca(2+) influx through stress activated and L-type voltage-dependent
      calcium channels and involves PKC and Src kinases.

PMID- 18625196
TI  - The unusual co-assembly of H- and M-chains in the ferritin molecule from the
      Antarctic teleosts Trematomus bernacchii and Trematomus newnesi.
AB  - Ferritins from the liver and spleen of the cold-adapted Antarctic teleosts
      Trematomus bernacchii and Trematomus newnesi have been isolated and
      characterized. Interestingly, only H- and M-chains are expressed and no L-chains.
      The H-chains contain the conserved ferroxidase center residues while M-chains
      harbor both the ferroxidase center and the micelle nucleation site ligands.
      Ferritins have an organ-specific subunit composition, they are: M homopolymers in
      spleen and H/M heteropolymers in liver. The M-chain homopolymer mineralizes iron
      at higher rate with respect to the H/M heteropolymer, which however is endowed
      with a lower activation energy for the iron incorporation process, indicative of
      a higher local flexibility. These findings and available literature data on
      ferritin expression in fish point to the role of tissue-specific expression of
      different chains in modulating the iron oxidation/mineralization process.

PMID- 18625197
TI  - Anthrax lethal toxin suppresses chemokine production in human neutrophil NB-4
      cells.
AB  - Microarray analysis was used to investigate the effects of Bacillus anthracis
      lethal toxin (LT) on human neutrophil-like NB-4 cells to identify markers of
      intoxication. Genes down-regulated after a 2h LT exposure included those encoding
      chemokines and transcription factors. Significant decreases in the mRNA of
      interleukin-8, CCL20, CCL3 and CCL4, which are important chemoattractants for
      immune cells, were observed using real-time PCR (12.3, 4.0, 4.1 and 2.2-fold
      (p<0.05), respectively). The decreases were more pronounced at 4 and 8h and were
      LT-specific. Decreases in chemokine protein levels were evident after 24h and
      were sensitive to low concentrations of LT. Co-incubation with an anti-lethal
      factor mAb at 500 and 250ng/ml restored levels of interleukin-8 to 100% and 50%,
      respectively. The results reveal that LT suppresses the cellular immune response
      and that this assay is a useful tool for the analysis of toxin-neutralising
      antibody activity in a biologically relevant system.

PMID- 18625198
TI  - Bone morphogenetic protein-4 strongly potentiates growth factor-induced
      proliferation of mammary epithelial cells.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit
      pleiotropic effects on biological processes such as cell proliferation, cell
      differentiation and tissue morphogenesis. With respect to cell proliferation,
      BMPs can exert either mitogenic or anti-mitogenic activities, depending on the
      target cells and their context. Here, we report that in low-density cultures of
      immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation
      by itself. However, when added in combination with suboptimal concentrations of
      fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or
      hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced
      cell proliferation. These results reveal a hitherto unsuspected interplay between
      BMP-4 and growth factors in the regulation of mammary epithelial cell
      proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic
      activity of multiple growth factors may contribute to mammary gland ductal
      morphogenesis as well as to breast cancer progression.

PMID- 18625199
TI  - Evidence of apoptosis and mitochondrial abnormalities in peripheral blood cells
      of Huntington's disease patients.
AB  - The mechanisms by which neurons die in Huntington's disease (HD) are uncertain,
      however, mitochondrial dysfunction and apoptosis have been implicated. Because
      peripheral abnormalities may reflect similar consequences of mutant huntingtin in
      the brain, we evaluated markers of apoptotic cell death and mitochondrial
      function in peripheral blood cells of 10 HD patients and 16 age- and gender
      matched controls. We found increased Bax expression in B and T lymphocytes, and
      monocytes from HD patients, but no alterations in Bcl-2 expression levels. B
      lymphocytes also showed decreased mitochondrial membrane potential. However, HD
      peripheral blood cells showed no differences in reactive oxygen species (ROS)
      levels when compared to controls. Our results suggest that peripheral blood
      cells, in particularly B lymphocytes may reflect changes observed in HD brain.

PMID- 18625200
TI  - Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow
      transplantation.
AB  - Autologous hematopoietic stem cell transplantation (HSCT) has recently been
      performed as a novel strategy to treat patients with new-onset type 1 diabetes
      (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes
      remains unknown. In order to help clarify the mechanism of remission-induction
      following autologous HSCT in patients with T1D, mice treated with multiple low
      doses of streptozotocin to induce diabetes were used as both donors (n=20) and
      recipients (n=20). Compared to streptozocin-treated mice not receiving
      transplantation, syngeneic bone marrow transplantation (syn-BMT) from a
      streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10
      after diabetes onset), can reverse hyperglycemia without relapse (P<0.001),
      maintain normal blood insulin levels (P<0.001), and preserve islet cell mass.
      Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of
      Tregs in spleens (P<0.01), increased Foxp3 mRNA expression (P<0.01) and increased
      Foxp3 protein expression (P<0.05). This diabetic-remission-inducing effect
      occurred in mice receiving bone marrow from either streptozocin-treated diabetic
      or non-diabetic normal donors. We conclude that autologous HSCT remission of
      diabetes is more than transient immune suppression, and is capable of prolonged
      remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.

PMID- 18625201
TI  - Induction of autophagy by B cell antigen receptor stimulation and its inhibition
      by costimulation.
AB  - Autophagy is a major pathway for degradation of cytoplasmic components, and is
      induced by some apoptotic stimuli mostly in cancer cells under the condition in
      which apoptosis is blocked. Ligation of the B cell antigen receptor (BCR) induces
      apoptosis and plays a crucial role in self-tolerance. However, whether BCR
      ligation induces autophagy is not clear. Here, we demonstrate that autophagosomes
      are extensively formed in normal mouse B cells as well as the WEHI-231 B cell
      line upon induction of BCR ligation-induced apoptosis regardless of whether
      apoptosis is blocked by overexpression of Bcl-2. In contrast, autophagosomes were
      not formed during apoptosis of spleen B cells cultured with medium alone or in
      BCR-ligated BAL17 cells which do not undergo apoptosis. Moreover, autophagy is
      not induced when apoptotic BCR signaling is abrogated by CD40 signaling. These
      results indicate that autophagy is induced specifically by apoptotic BCR
      signaling even in unmanipulated normal B cells.

PMID- 18625202
TI  - HMG-CoA reductase inhibitor simvastatin overcomes bortezomib-induced apoptosis
      resistance by disrupting a geranylgeranyl pyrophosphate-dependent survival
      pathway.
AB  - Simvastatin is a competitive inhibitor of HMG-CoA reductase, the rate-limiting
      enzyme of the mevalonate pathway required for the biosynthesis of cholesterol and
      higher isoprenoids such as geranylgeranyl pyrophosphate (GGPP). Apart from its
      capacity to lower cholesterol plasma levels and to protect against cardiovascular
      disease, simvastatin induces apoptosis in various cancer cells. We have generated
      human Namalwa Burkitt lymphoma cells that display general apoptosis resistance
      and hyperproliferation due to increased expression and proteolytic activity of
      26S proteasomes in response to continuous treatment of the cells with the
      proteasome inhibitor bortezomib. In these cells, simvastatin does not inhibit
      proteasome activity, but induces apoptosis, G2/M cell cycle arrest and
      accumulation of p21(Waf1/Cip1), and effectively inhibits hyperproliferation.
      These effects are reversed by the addition of GGPP. GGPP-dependent plasma
      membrane localization of the small GTPase RhoA that is required for RhoA-mediated
      oncogenic signaling is completely inhibited by simvastatin. Finally, bortezomib
      but not simvastatin induces accumulation and stabilization of the anti-apoptotic
      protein Mcl-1, which is known to confer resistance to apoptosis in cancer cells.
      Thus, simvastatin overcomes bortezomib-induced apoptosis resistance by inhibiting
      synthesis of GGPP and disrupting a GGPP-dependent survival pathway.

PMID- 18625203
TI  - Characterization of a specific interaction between IP-L, a tobacco protein
      localized in the thylakoid membranes, and Tomato mosaic virus coat protein.
AB  - We previously demonstrated a specific interaction between Tomato mosaic virus
      (ToMV) coat protein (CP) and a tobacco protein designated IP-L that may be
      involved in the long-distance movement of ToMV. Here, using the yeast two-hybrid
      system and GST pull-down assay, we demonstrated that the N-terminal helical
      region (residues 3-18) of IP-L is required for the interaction, while two alpha
      helical domains (residues 21-31 and 142-147) of ToMV CP are involved.
      Furthermore, using immunoblotting, we showed that both of the IP-L and the
      majority of ToMV CP are co-localized in the chloroplast thylakoid membranes.
      These results provide further evidence for the association between tobamovirus
      CPs and thylakoid membrane components, which has been shown to be involved in
      chlorosis formation during viral infection, and indicate that the interaction
      between ToMV CP and IP-L may affect chloroplast function and stability and thus
      leading to chlorosis.

PMID- 18625204
TI  - Dissecting the regulation of yeast genes by the osmotin receptor.
AB  - The Izh2p protein from Saccharomyces cerevisiae is a receptor for the plant
      antifungal protein, osmotin. Since Izh2p is conserved in fungi, understanding its
      biochemical function could inspire novel strategies for the prevention of fungal
      growth. However, it has been difficult to determine the exact role of Izh2p
      because it has pleiotropic effects on cellular biochemistry. Herein, we
      demonstrate that Izh2p negatively regulates functionally divergent genes through
      a CCCTC promoter motif. Moreover, we show that Izh2p-dependent promoters
      containing this motif are regulated by the Nrg1p/Nrg2p and Msn2p/Msn4p
      transcription factors. The fact that Izh2p can regulate gene expression through
      this widely dispersed element presents a reasonable explanation of its
      pleiotropy. The involvement of Nrg1p/Nrgp2 in Izh2p-dependent gene regulation
      also suggests a role for this receptor in regulating fungal differentiation in
      response to stimuli produced by plants.

PMID- 18625205
TI  - Ethyl pyruvate and ethyl lactate down-regulate the production of pro-inflammatory
      cytokines and modulate expression of immune receptors.
AB  - Esters of alpha-oxo-carbonic acids such as ethyl pyruvate (EP) have been
      demonstrated to exert inhibitory effects on the production of anti-inflammatory
      cytokines. So far, there is no information about effects, if any, of ethyl
      lactate (EL), an obviously inactive analogue of EP, on inflammatory immune
      responses. In the present study, we provide evidence that the anti-inflammatory
      action of alpha-oxo-carbonic acid esters is mediated by inhibition of glyoxalases
      (Glo), cytosolic enzymes that catalyse the conversion of alpha-oxo-aldehydes such
      as methylglyoxal (MGO) into the corresponding alpha-hydroxy acids using
      glutathione as a cofactor. In vitro enzyme activity measurements revealed the
      inhibition of human Glo1 by alpha-oxo-carbonic acid esters, whilst alpha-hydroxy
      carbonic acid esters such as EL were not inhibitory. In contrast, both EP and EL
      were shown to suppress the Lipopolysaccharide (LPS)-induced production of pro
      inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)
      1beta, IL-6 and IL-8 from human immunocompetent cells, and modulated the
      expression of the immune receptors HLA-DR, CD14 and CD91 on human monocytes.
      Here, we show a crossing link between glyoxalases and the immune system. The
      results described herein introduce glyoxalases as a possible target for
      therapeutic approaches of immune suppression.

PMID- 18625206
TI  - Independent components in stimulus-related BOLD signals and estimation of the
      underlying neural responses.
AB  - We measured blood oxygen level dependent (BOLD) responses to the onset of dynamic
      noise stimulation in defined regions of the primary retinotopic projection (V1)
      in visual cortex. The response waveforms showed a remarkable diversity across
      stimulus types, violating the basic assumption of a unitary general linear model
      of a uniform BOLD response function convolved with each stimulus sequence. We
      used independent component analysis (ICA) to analyze the component mechanisms
      contributing to these responses. The underlying neural responses for the
      components were estimated by nonlinear optimization through the Friston-Buxton
      hemodynamic model of the BOLD response. Our analysis suggests that one of the
      identified components reflected a sustained neural response to the stimulus and
      that another reflected an extremely slow neural response. A third component
      exhibited nonlinear change-specific transient responses. The first two components
      showed stable spatial structure in the V1 region of interest with respect to the
      eccentricity of the noise stimulus.

PMID- 18625207
TI  - Examining the role of the medial thalamus in modulating the affective dimension
      of pain.
AB  - The purpose of this project was to explore the role of the medial thalamus (MT),
      including the medial dorsal thalamus (MD) and associated midline nuclei in pain
      processing. Experiment 1 explored the role of electrolytic lesions to the MT in
      the formalin test. It was hypothesized that animals with electrolytic lesions to
      the MT would have attenuated paw licking behavior during the second phase of the
      formalin tests as compared to sham lesion controls. This hypothesis was based on
      evidence of projections from the MD to the ACC, and previous research
      demonstrating attenuation of paw licking behavior in the second phase of the
      formalin test in animals with ACC lesions. Experiment 2 tested the effects of
      electrolytic MT lesions on mechanical paw withdrawal thresholds in the L5 nerve
      ligation model. It was hypothesized that lesions of the MT would not alter
      mechanical paw withdrawal thresholds. Experiment 3 tested the effects of
      electrolytic MT lesions on escape/avoidance behavior in the place escape
      avoidance paradigm. For experiment 1, animals with MT lesions were found to have
      slightly elevated paw licking behavior, but only across two time points. No
      differences in mechanical paw withdrawal thresholds and in escape/avoidance
      behavior were detected as compared to the sham lesion group. These results
      indicate a limited role for the medial thalamic nuclei in coding for pain
      intensity and the affective dimension of pain. Additional research is needed to
      explore the role of individual medial nuclei in pain processing.

PMID- 18625208
TI  - A short review of slow phase synchronization and memory: evidence for control
      processes in different memory systems?
AB  - An integrative theoretical approach about memory related oscillations is
      presented. The basic assumptions are that memory related oscillations are
      probably confined to theta and upper alpha and that other frequencies
      particularly in the gamma range are important for memory primarily because they
      become coupled to lower frequencies and/or because they play a specific role for
      a high precision timing of neural events (including phenomena such as LTP or
      LTD). In contrast to previous studies, where we related theta and upper alpha to
      a variety of different memory processes, we suggest here that these oscillations
      are associated with top-down control processes in two large storage systems,
      working memory (WM) and long-term memory (LTM). These systems may have their own
      types of top-down processes that control access to and/or manipulation of stored
      information. The hypothesis, suggested here is that theta and upper alpha reflect
      these processes which can be best studied when analyzing phase.

PMID- 18625209
TI  - Mechanical resonance enhances the sensitivity of the vibrissa sensory system to
      near-threshold stimuli.
AB  - The representation of high-frequency sensory information is a crucial problem
      faced by the nervous system. Rodent facial vibrissae constitute a high-resolution
      sensory system, capable of discriminating and detecting subtle changes in tactual
      input. During active sensing, the mechanical properties of vibrissae may play a
      key role in filtering sensory information and translating it into neural
      activity. Previous studies have shown that rat vibrissae resonate, conferring
      frequency specificity to trigeminal ganglion (NV) and primary somatosensory
      cortex (SI) neurons during suprathreshold sensory stimulation. In addition to
      frequency specificity, a further potential impact of vibrissa resonance is
      enhancement of sensitivity to near-threshold stimuli through signal
      amplification. To examine the effect of resonance on peri-threshold inputs
      (<or=80 microm at the vibrissa tip), we recorded NV and SI neurons during
      stimulation at multiple amplitudes and frequencies, and generated minimal
      amplitude tuning curves. Several novel findings emerged from this study. First,
      vibrissa resonance significantly lowered the threshold for evoked neural
      activity, in many cases by an order of magnitude compared to stimuli presented at
      off-resonance frequencies. When stimulated at the fundamental resonance
      frequency, motions as small as 8 microm at the vibrissa tip, corresponding to
      angular deflections of less than 0.2 degrees, drove neural firing in the
      periphery and cortex. Second, a closer match between vibrissal and neural
      frequency tuning was found for lower amplitude motions. Third, simultaneous
      paired recordings demonstrated that the minimal amplitude of resonant vibrissa
      stimulation required to evoke responses in SI increased significantly for
      recordings outside the primary vibrissa barrel column, providing additional
      evidence for somatotopically localized frequency columns. These data demonstrate
      that resonant amplification can increase the sensitivity of the vibrissa sensory
      system to an ecologically relevant range of low-amplitude, high-frequency
      stimuli.

PMID- 18625210
TI  - Control of glial precursor cell development in the mouse optic nerve by sonic
      hedgehog from retinal ganglion cells.
AB  - The development of glial precursor cells in the mammalian optic nerve depends on
      retinal ganglion cell (RGC) axons, but the signals that mediate this neuron-to
      glia interaction have not been fully characterized. Sonic hedgehog (Shh) is
      expressed by RGCs, and we showed previously that it is required for the
      specification of astrocyte lineage cells at the optic disc. To study the role of
      RGC-derived Shh on astrocyte development at later developmental stages, we
      generated mice with a conditional ablation of Shh in the peripheral retina and
      analyzed gene expression and glial cell development in the optic nerve. Astrocyte
      development was initiated in the optic nerves of these mutant mice; however, the
      expression of Hedgehog (Hh) target genes, Gli1 and Ptch1 and cell cycle genes,
      Ccnd1 and Cdc25b in the optic nerves were downregulated. Astrocyte proliferation
      was markedly reduced. Oligodendrocyte precursor cells were fewer in the optic
      nerves of mutant mice, possibly as a consequence of reduced secretion of growth
      factors by astrocytes. At a later developmental stage, optic nerve axons
      displayed signs of Wallerian degeneration, including reduction of astrocyte
      processes, degenerating glial cells and formation of distended axons. We also
      demonstrate that the Hh pathway can be activated in optic nerve-derived
      astrocytes in vitro, but fails to induce cell cycle gene expression and
      proliferation. RGC-derived Shh signalling isthus necessary in vivo for
      maintenance of astrocyte proliferation, affecting both axo-glial and normal glial
      cell development in the optic nerve.

PMID- 18625212
TI  - Influence of visual contextual cues on haptic discrimination of orientations in 5
      month-old infants.
AB  - The present research addressed the question of the influence of visual contextual
      cues on the manual discrimination of spatial orientations in 5-month-old infants.
      Different types of visual contextual cues were proposed during the haptic
      discrimination task: congruent-informative, non congruent-informative or
      noninformative. A familiarization (with a 60-s fixed-duration)/reaction to
      novelty procedure was used in three experiments. In Experiment 1, a congruent
      informative visual context (a visual context composed of alternate black and
      white stripes tilted to 20 degrees -left) was present and a haptic discrimination
      between a 20 degrees -left rod and a 30 degrees -left rod was observed (this
      discrimination was absent without visual context in Gentaz and Streri's study,
      2004). In Experiment 2, the visual context cues (composed of black dots) were
      noninformative, and infants could not discriminate these two oblique rods. In
      Experiment 3, the presence of a non congruent visual context (a visual context
      composed of alternate black and white stripes tilted to 20 degrees -left, as in
      Experiment 1) disturbed the gravitational vertical perception usually observed:
      infants could not discriminate the vertical rod from the 10 degrees -left rod.
      These results showed that only the informative (congruent and non congruent)
      visual contextual cues influenced the haptic discrimination of spatial
      orientations in 5-month-old infants. These results are discussed in relation with
      data observed in adults and with the current models of the multisensorial
      integration and attentional level.

PMID- 18625211
TI  - Nesfatin-1 inhibits NPY neurons in the arcuate nucleus.
AB  - Although the novel satiety factor nesfatin-1 has been shown to influence feeding
      behavior through effects on melanocortin signaling, the specific hypothalamic
      neuronal substrates through which such effects are mediated have yet to be
      elucidated. To identify neuronal cell types potentially important in mediating
      nesfatin-1's effects, whole cell current clamp recordings were made from
      hypothalamic arcuate nucleus neurons and the effects of bath applied nesfatin-1
      on membrane excitability determined. Neurons then underwent phenotypic
      identification post hoc using single cell RT-PCR. Nesfatin-1 (10 nM) had effects
      on the majority of arcuate nucleus neurons tested, with most responsive cells
      hyperpolarizing following exposure. Furthermore, 9 of 11 identified NPY neurons
      hyperpolarized in response to nesfatin-1 exposure. Pharmacological experiments
      revealed that glibenclamide (500 nM), an ATP-sensitive potassium conductance
      antagonist, prevented nesfatin-1-induced hyperpolarization. Therefore, nesfatin-1
      induced inhibition of feeding may be mediated through the inhibition of
      orexigenic NPY neurons.

PMID- 18625213
TI  - Brain activity and temporal coupling related to eye movements during REM sleep:
      EEG and MEG results.
AB  - EEG and MEG REM sleep gamma activity was studied immediately before rapid eye
      movement onset (PRE-EM), during REM sleep with eye movements away from eye
      movement onset -phasic-REM (Ph-REM)--and during REM sleep without eye movements,
      or tonic REM (T-REM). For this purpose, activity was segmented into three
      different time windows: of 62.5, 250 and 500 ms. Two strategies were used: one a
      statistical comparison of changes between T-REM, Ph-REM and PRE-EM; the other a
      descriptive approach using principal component analysis. Significant findings
      showed that both EEG and MEG gamma activity are higher directly before eye
      movement onset in PRE-EM periods and during Ph-REM than during T-REM; temporal
      coupling of electrical activity between the frontal and parietal regions is
      decreased, while temporal coupling between the right frontal and midline is
      increased. Just before eye movement onset, larger recording sites become related.
      For the first time, results showed a close temporal link between power and
      temporal coupling of fast oscillations andrapid eye movements in REM sleep,
      indicating increased activation, uncoupling between the left frontal executive
      areas and posterior sensory association regions and increased coupling between
      the right frontal attentional and midline alerting systems. Brain activity is
      reorganized by phasic events.

PMID- 18625214
TI  - Repulsive and attractive semaphorins cooperate to direct the navigation of
      cardiac neural crest cells.
AB  - The cardiac neural crest, a subpopulation of the neural crest, contributes to the
      cardiac outflow tract formation during development. However, how it follows the
      defined long-range migratory pathway remains unclear. We show here that the
      migrating cardiac neural crest cells (NCCs) express Plexin-A2, Plexin-D1 and
      Neuropilin. The membrane-bound ligands for Plexin-A2, Semaphorin (Sema)6A and
      Sema6B, are expressed in the dorsal neural tube and the lateral pharyngeal arch
      mesenchyme (the NCC "routes"). Sema3C, a ligand for Plexin-D1/neuropilin-1, is
      expressed in the cardiac outflow tract (the NCC "target"). Sema6A and Sema6B
      repel neural crest cells, while Sema3C attracts neural crest cells. Sema6A and
      Sema6B repulsion and Sema3C attraction are diminished either when Plexin-A2 and
      Neuropilin-1, or when Plexin-D1, respectively, are knocked down in NCCs. When
      RNAi knockdown diminishes each receptor in NCCs, the NCCs fail to migrate into
      the cardiac outflow tract in the developing chick embryo. Furthermore, Plexin-A2
      deficient mice exhibit defects of cardiac outflow tract formation. We therefore
      conclude that the coordination of repulsive cues provided by Sema6A/Sema6B
      through Plexin-A2 paired with the attractive cue by Sema3C through Plexin-D1 is
      required for the precise navigation of migrating cardiac NCCs.

PMID- 18625215
TI  - Role of alpha2-adrenoceptors in enhancement of antinociceptive effect in diabetic
      mice.
AB  - The present studies investigated behavioral and neurochemical aspects of the
      noradrenergic and serotonergic nervous systems in streptozotocin-induced diabetic
      mice. We previously reported that intrathecal (i.t.) injection of norepinephrine
      significantly potentiated antinociception in diabetic mice compared to that in
      non-diabetic mice, and that antinociception due to norepinephrine injection was
      completely abolished by pretreatment with yohimbine, an alpha2-adrenoceptor
      antagonist. The present studies demonstrated that i.t. injection of clonidine
      also showed more-potent antinociceptive activity in diabetic mice than in non
      diabetic mice, but that i.t. methoxamine injection did not affect diabetic or non
      diabetic mice. The antinociceptive potency due to i.t. injection of 5-HT was
      significantly lower in diabetic than in non-diabetic mice. In a neurochemical
      study, we found that the density of [3H]-rauwolscine binding sites in spinal
      alpha2-adrenoceptors was significantly higher in diabetic than in non-diabetic
      mice, but that the binding affinity was unchanged. Spinal norepinephrine turnover
      was determined by measuring the decline in tissue norepinephrine concentration at
      3 h after injection of the tyrosine hydroxylase inhibitor alpha-methyl-p
      tyrosine. The spinal norepinephrine concentration decreased to 43.7% from the
      baseline in non-diabetic mice, while it was 21.0% in diabetic mice. These results
      suggest that, based on the decrease of norepinephrine release in the spinal cord,
      up-regulation of spinal alpha2-adrenoceptors caused the increase of
      antinociception due to i.t. injection of an alpha2-adrenoceptor agonist in
      streptozotocin-induced diabetic mice, and it seemed that the stimulation of
      alpha2-adrenoceptors potentiated the antinociceptive effect. Thus, the spinal
      noradrenergic systems play an important moderating role in diabetes-induced
      neuropathic pain.

PMID- 18625216
TI  - Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra
      chinensis Baill.
AB  - Schisandrin is the main active ingredient isolated from the fruit of Schisandra
      chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti
      oxidative effects in vivo. In the present study, the effect of schisandrin on
      plasma nitrite concentration in lipopolysaccharide (LPS)-treated mice was
      evaluated. It also significantly inhibited carrageenan-induced paw edema and
      acetic acid-induced vascular permeability in mice. Furthermore, schisandrin had a
      protective effect on lipopolysaccharide (LPS)-induced sepsis. In vitro, our
      results are the first that show that the anti-inflammatory properties of
      schisandrin result from the inhibition of nitric oxide (NO) production,
      prostaglandin E(2) (PGE(2)) release, cyclooxygenase-2 (COX-2) and inducible
      nitric oxide synthase (iNOS) expression, which in turn results from the
      inhibition of nuclear factor-kappaB (NF-kappaB), c-Jun N-terminal kinase (JNK)
      and p38 mitogen-activated protein kinase (MAPK) activities in a RAW 264.7
      macrophage cell line.

PMID- 18625217
TI  - Eckol protects V79-4 lung fibroblast cells against gamma-ray radiation-induced
      apoptosis via the scavenging of reactive oxygen species and inhibiting of the c
      Jun NH(2)-terminal kinase pathway.
AB  - The radioprotective effect of eckol against gamma-ray radiation-induced oxidative
      stress and its possible protective mechanisms were investigated. Eckol was found
      to reduce the intracellular reactive oxygen species generated by gamma-ray
      radiation. Moreover, eckol also protected against radiation-induced cellular DNA
      damage and membrane lipid peroxidation, which are the main targets of radiation
      induced damage. In addition, eckol recovered the cell viability damaged by
      radiation via the inhibition of apoptosis. Irradiated cells with eckol treatment
      reduced the expression of bax, the activation of caspase 9 and caspase 3, which
      were induced by radiation. However, irradiated cells with eckol recovered the
      expression of bcl-2 and mitochondrial cytochrome c which were decreased by
      radiation. The anti-apoptotic effect of eckol exerted via the inhibition of
      mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase
      (JNK)-activator protein 1 (AP-1) cascades induced by radiation. In summary, the
      results suggest that eckol protects cells against the oxidative stress induced by
      radiation via the reduction of reactive oxygen species and the attenuation of
      activation in SEK1-JNK-AP-1 pathway.

PMID- 18625218
TI  - Pinocembrin prevents glutamate-induced apoptosis in SH-SY5Y neuronal cells via
      decrease of bax/bcl-2 ratio.
AB  - Pinocembrin is the most abundant flavonoids in propolis, and has been proven to
      have antioxidant, antibacterial and anti-inflammatory property. To assess the
      protective effects of pinocembrin on neurons, SH-SY5Y neuronal cells were
      pretreated with pinocembrin for 2 h followed by co-treatment with glutamate (2
      mM) for 12 h. Cell viability was determined by(3,4,5-dimethylthiazol-2-yl)-2,5
      diphenylte-trazolium bromide assay, and apoptosis was confirmed by cell
      morphology, capillary zone electrophoresis and flow cytometry assay. Cell
      morphology was evaluated with Hoechst33258/PI dye. Treatment with pinocembrin
      (10(-5), 10(-6), 10(-7) mol/l) increased cell viability dose-dependently,
      inhibited LDH release and attenuated apoptosis. Intracellular free [Ca(2+)] was
      increased after glutamate exposure, and this increase was attenuated in cells
      treated with pinocembrin. bax mRNA expression increased remarkably following
      glutamate exposure and pinocembrin treatment manifested a reduction effect. bcl-2
      mRNA expression changes were not detected in groups with or without pinocembrin.
      Western blotting results indicated that pinocembrin treatment reduced the
      expression of Bax and had no effect on Bcl-2, thus decreased the Bax-Bcl-2 ratio,
      which is in consistent with the gene expression result. Pinocembrin could also
      down-regulate the expression of p53 protein, and inhibit the release of
      cytochrome c from mitochondria to cytosol. Thus we conclude that pinocembrin
      exerts its neuroprotective effects in glutamate injury model partly by inhibiting
      p53 expression, thus Bax-Bcl-2 ratio, and the release of cytochrome c.

PMID- 18625219
TI  - IQGAP1 activates Tcf signal independent of Rac1 and Cdc42 in injury and repair of
      bronchial epithelial cells.
AB  - The process of injury and repair involves spreading, migration and cell
      proliferation. The functions of Rho GTPases and their effector IQGAP1 are poor
      known in this process of airway epithelium. In the present study, we employed a
      widely used in vitro model by scratching a monolayer of BECs. We found that
      scratching induced decreasing of the GTP-bound Rac1 and Cdc42, but increasing the
      amounts of IQGAP1 at different time points. Next, we confirmed that IQGAP1
      interacted with the constitutively active Rac1 (Rac1(V12)) and Cdc42 (Cdc42(V12))
      rather than the dominant negative Rac1 (Rac1(N17)) and Cdc42 (Cdc42(N17)). Over
      expressions of wild type (WT) IQGAP1 and its mutant (T1050AX2), which was
      defective to interact with Rho GTPases, induced translocation of beta-catenin
      from the cytoplasm into the nucleus. These results activated Tcf/Lef and
      increased the expression levels of its target genes of c-myc and cyclin D1.
      Likewise, the amounts of c-myc and cyclin D1 increased after scratching. Our
      results suggested that IQGAP1 mediated cell proliferation through activating Tcf
      in a manner independent of Rac1 and Cdc42 in wound repair of BECs.

PMID- 18625220
TI  - The role of peroxisome proliferator-activated receptor-beta/delta in epidermal
      growth factor-induced HaCaT cell proliferation.
AB  - Epidermal growth factor (EGF) has been shown to be a potent mitogen for epidermal
      cells both in vitro and in vivo, thus contributing to the development of an
      organism. It has recently become clear that peroxisome proliferator-activated
      receptor-beta/delta (PPARbeta/delta) expression and activation is involved in the
      cell proliferation. However, little is known about the role of PPARbeta/delta in
      EGF-induced proliferation of HaCaT keratinocytes. In this study, HaCaT cells were
      cultured in the presence and absence of EGF and we identified that EGF induced an
      increase of PPARbeta/delta mRNA and protein level expression in time-dependent
      and dose-dependent manner, and AG1487, an EGF receptor (EGFR) special inhibitor,
      caused attenuation of PPARbeta/delta protein expression. Electrophoretic mobility
      shift assay (EMSA) revealed that EGF significantly increased PPARbeta/delta
      binding activity in HaCaT keratinocytes. Antisense phosphorothioate
      oligonucleotides (asODNs) against PPARbeta/delta caused selectively inhibition of
      PPARbeta/delta protein content induced by EGF and significantly attenuated EGF
      mediated cell proliferation. Treatment of the cells with L165041, a specific
      synthetic ligand for PPARbeta/delta, significantly enhanced EGF-mediated cell
      proliferation. Finally, c-Jun ablation inhibited PPARbeta/delta up-regulation
      induced by EGF, and chromatin immunoprecipitation (ChIP) showed that c-Jun bound
      to the PPARbeta/delta promoter and the binding increased in EGF-stimulated cells.
      These results demonstrate that EGF induces PPARbeta/delta expression in a c-Jun
      dependent manner and PPARbeta/delta plays a vital role in EGF-stimulated
      proliferation of HaCaT cells.

PMID- 18625221
TI  - Long-term cognitive dysfunction following experimental subarachnoid hemorrhage:
      new perspectives.
AB  - Cognitive dysfunction is increasingly recognized as a significant long-term
      complication following subarachnoid hemorrhage (SAH), affecting up to 60% of
      survivors. We proposed to determine the incidence and explore potential
      mechanisms of cognitive dysfunction in a rat model. The effects of intracisternal
      blood, saline and sham injections were compared. At five weeks, Morris water maze
      escape latency (P=0.001) and swimming distance (P=0.001) were significantly
      different between groups, with increased latencies and distances recorded in the
      blood group in spite of increased swimming speed. The number of morphologically
      intact cortical (r=-0.75, P=0.0001) and hippocampal CA1 (r=-0.80, P<0.0001)
      neurons correlated with escape latency. In spite of only slight early reductions
      in proximal cerebral arterial diameters, pronounced and prolonged reductions in
      regional cerebral blood flow were observed in SAH rats, suggesting microvascular
      dysfunction. In concordance, cerebral microangiographic perfusion remained
      incomplete even after 2 weeks. 8-hydroxydeoxyguanosine immunohistochemistry also
      revealed microvascular as well as neuronal oxidative DNA damage. These results
      provide new insights into the pathogenesis of cognitive dysfunction in SAH. They
      reveal a surprisingly prolonged time course of diffuse cerebrovascular
      insufficiency, most likely due to reversible microvascular dysfunction. Similar
      to findings in experimental models of vascular dementia, the data indicate a
      potentially important role for prolonged cerebrovascular insufficiency, probably
      due to microvascular dysfunction, and selective cortical and subcortical neuronal
      loss in cognitive failure following SAH.

PMID- 18625222
TI  - Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional
      study in patients with neurodegeneration.
AB  - Because accumulation of alpha-synuclein (alphaS) in the brain is a hallmark of
      Parkinson disease (PD) and related disorders, we examined its occurrence in human
      cerebrospinal fluid (CSF). Following affinity enrichment and trypsin digestion of
      CSF collected from a neurologically healthy donor, we identified several alphaS
      derived peptides by mass spectrometry. The concentration of alphaS amounted to
      <0.001% of the CSF proteome. We then built, validated and optimized a sandwich
      type, enzyme-linked immunoadsorbent assay (ELISA) to measure total alphaS levels
      in unconcentrated CSF. In a cross-sectional study of 100 living donors, we
      examined cell-free CSF samples from subjects clinically diagnosed with advanced
      PD, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and a group of non
      neurodegenerative disease controls (NCO). In these four groups the CSF alphaS
      concentrations ranged from 0.8 to 16.2 pg/microl. Mean CSF alphaS values were
      lower in donors with a primary synucleinopathy (PD, DLB: n=57) than in the other
      two groups (AD, NCO: n=35; p=0.025). By contrast, living Creutzfeldt-Jakob
      disease patients showed markedly elevated CSF alphaS levels (n=8; mean, 300
      pg/microl; p<0.001). Our results unequivocally confirm the presence of alphaS in
      adult human CSF. In a first feasibility study employing a novel ELISA, we found
      relatively low CSF alphaS concentrations in subjects with parkinsonism linked to
      synucleinopathy, PD and DLB. In definite prion disease cases, we recorded a
      marked rise in total CSF alphaS resulting from rapid cell death. Our results will
      likely aid future biomarker explorations in neurodegenerative conditions and
      facilitate target validation studies.

PMID- 18625223
TI  - Nordihydroguaiaretic acid increases glutamate uptake in vitro and in vivo:
      therapeutic implications for amyotrophic lateral sclerosis.
AB  - Synaptic accumulation of glutamate causes neuronal death in many
      neurodegenerative pathologies including amyotrophic lateral sclerosis. Drugs
      capable of increasing glutamate uptake could therefore be therapeutically
      effective. We screened in a cell-based assay a library of 1040 FDA-approved drugs
      and nutrients for compounds that could enhance glutamate uptake.
      Nordihydroguaiaretic acid (NDGA), an anti-inflammatory drug that inhibits
      lipoxygensases, potently enhanced glutamate uptake in MN-1 cells. Given
      subcutaneously at 1 mg/day for 30 days in mice, NDGA increased glutamate uptake
      in spinal cord synaptosomes persistently throughout the treatment. However, when
      administered following the same regimen to the SOD1-G93A transgenic mouse model
      of ALS at disease onset, NDGA did not extend survival of these mice. We found
      that NDGA failed to sustain increased glutamate uptake in the SOD1-G93A mice
      despite an initial upregulation measured during the first 10 days of treatment.
      SOD1-G93A mice displayed a progressive increase in spinal cord expression levels
      of the efflux transporter P-glycoprotein beginning at disease onset. This
      increase was not mediated by the NDGA treatment because it was measured in
      untreated SOD1-G93A mice. Since P-glycoproteins control the extrusion of a broad
      range of toxins and xenobiotics and are responsible for drug resistance in many
      diseases including cancer and brain diseases such as epilepsy, we propose that
      the failure of NDGA in maintaining glutamate uptake upregulated in SOD1-G93A mice
      and its therapeutic inefficacy are due to acquired pharmacoresistance mediated by
      the increased expression of P-glycoprotein.

PMID- 18625224
TI  - Noradrenergic denervation facilitates the release of acetylcholine and serotonin
      in the hippocampus: towards a mechanism underlying upregulations described in MCI
      patients?
AB  - Patients with mild cognitive impairment (MCI), who are at risk for Alzheimer's
      disease (AD), or those with early AD, exhibit noradrenergic degeneration in the
      locus coeruleus. In MCI patients, upregulations of cholinergic and serotonergic
      functions were described in the hippocampus. To investigate the effects of
      selective noradrenergic denervation on hippocampal neurotransmitter functions,
      rats were treated with 50 mg/kg (i.p.) of N-2-chlorethyl-N-ethyl-2
      bromobenzylamin (DSP-4). DSP-4 treatment reduced hippocampal noradrenaline (NA)
      by more than 90% (vs. controls), whereas dopamine and 5-HT levels were
      unaffected. The accumulation and electrically-evoked release (in nCi) of [(3)H]
      NA in hippocampal slices were strongly reduced. Accumulation of [(3)H]-5-HT was
      reduced in DSP-4 rats, whereas spontaneous and electrically-evoked release of
      [(3)H]-5-HT was significantly enhanced, probably due to a weaker effect of
      endogenous NA via alpha(2)-adrenoceptors on serotonergic terminals. Accordingly,
      the alpha(2)-agonist UK-14,304 [5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline]
      more potently inhibited the evoked 5-HT release in DSP-4 rats, whereas the
      alpha(2)-antagonist idazoxan failed to exert facilitatory effects. Most
      surprisingly, the accumulation of [(3)H]-choline, and both the basal and
      electrically-evoked overflow of [(3)H] from hippocampal slices preincubated with
      [(3)H]-choline, were also significantly increased in DSP-4 rats. These
      observations suggest that noradrenergic damage in the locus coeruleus may
      facilitate cholinergic and serotonergic functions in the hippocampus. Although
      the current lesion model does not mimic the protracted evolution of
      neurodegenerative processes in MCI and AD, our data could point to an explanation
      for the upregulations of cholinergic and serotonergic functions described in the
      hippocampus of MCI patients.

PMID- 18625225
TI  - PEG10 directly regulated by E2Fs might have a role in the development of
      hepatocellular carcinoma.
AB  - PEG10 is an imprinted gene which is up-regulated in hepatocelluar carcinoma
      (HCC). However, the mechanism of PEG10 regulation remains to be elucidated. In
      this work the transcription factors E2F-1 and -4 were demonstrated to bind
      directly to the promoter of PEG10 and thereby regulate its expression. The
      expression profile of HCC tissues also suggested E2Fs were involved in PEG10
      regulation. Further functional analysis showed that PEG10 was involved in the
      repression of apoptosis induced by serum deprivation and chemotherapeutic drugs.
      These findings link cancer genetics and epigenetics by showing that E2F acts
      directly upstream of an anti-apoptosis imprinted gene, PEG10.

PMID- 18625226
TI  - NADPH-dependent thioredoxin reductase and 2-Cys peroxiredoxins are needed for the
      protection of Mg-protoporphyrin monomethyl ester cyclase.
AB  - The chloroplast-localized NADPH-dependent thioredoxin reductase (NTRC) has been
      found to be able to reduce hydrogen peroxide scavenging 2-Cys peroxiredoxins. We
      show that the Arabidopsis ntrc mutant is perturbed in chlorophyll biosynthesis
      and accumulate intermediates preceding protochlorophyllide formation. A specific
      involvement of NTRC during biosynthesis of protochlorophyllide is indicated from
      in vitro aerobic cyclase assays in which the conversion of Mg-protoporhyrin
      monomethyl ester into protochlorophyllide is stimulated by addition of the NTRC/2
      Cys peroxiredoxin system. These findings support the hypothesis that this NADPH
      dependent hydrogen peroxide scavenging system is particularly important during
      periods with limited reducing power from photosynthesis, e.g. under chloroplast
      biogenesis.

PMID- 18625227
TI  - Helix swapping leads to dimerization of the N-terminal domain of the c-type
      cytochrome maturation protein CcmH from Escherichia coli.
AB  - In the process of cytochrome c maturation, heme groups are covalently attached to
      reduced cysteines of specific heme-binding motifs (CXXCH) in an apocytochrome c
      sequence. In Escherichia coli, the CcmH protein maintains apo-protein cysteines
      in a reduced state prior to heme attachment. We have purified and biophysically,
      as well as structurally characterized the soluble, N-terminal domain of E. coli
      CcmH that carries the functionally relevant LRCXXC-motif. In contrast to a
      recently presented structure of the homologous domain from Pseudomonas
      aeruginosa, the E. coli protein forms a tightly interlinked dimer by swapping its
      N-terminal helix between two monomers. We propose that an altered environment of
      the functional motif may help to discern between the two redox partners CcmG and
      apocytochrome c.

PMID- 18625228
TI  - Mutagenesis of Gln294 of the reverse transcriptase of human immunodeficiency
      virus type-2 and its effects on the ribonuclease H activity.
AB  - Despite the high homology between human immunodeficiency virus type-1 (HIV-1) and
      human immunodeficiency virus type-2 (HIV-2) reverse transcriptases (RTs), the
      ribonuclease H (RNase H) level of HIV-2 RT is lower than that of HIV-1 RT, while
      the DNA polymerase of both RTs is similar. We conducted mutagenesis of HIV-2 RT
      Gln294 (shown to control the RNase H activity level when modified to a Pro in the
      smaller p54 subunit and not in the larger p68 subunit) to various residues, and
      assayed the activities of all mutants. All exhibited an RNase H that is higher
      than the wild-type (WT) HIV-2 RT level, although the DNA polymerase of all
      mutants equals WT HIV-2 RT level. These results represent a unique case, where
      every mutation induces an increase rather than a decrease in an enzyme's
      activity.

PMID- 18625230
TI  - Ehhmbp45 is a novel hemoglobin-binding protein identified in Entamoeba
      histolytica.
AB  - Hemoglobin-binding proteins are necessary for pathogens to obtain iron from Hb.
      Entamoeba histolytica can grow using Hb as source of iron, but the underlying
      mechanism has not previously been established. In this work, we identified a 45
      kDa Hb-binding protein of E. histolytica, which we named Ehhmbp45. In silico
      analysis showed that Ehhmbp45 contains the conserved domains needed for Hb
      binding, while overlay assays demonstrated that Ehhmbp45 is able to bind Hb. In
      addition, we found that Ehhmbp45 mRNA levels were up-regulated under iron
      starvation conditions and were subsequently restored to basal levels when Hb was
      added to the cell cultures. These findings provide the first insights on the role
      of Ehhmbp45 in iron acquisition from Hb.

PMID- 18625229
TI  - Deletion of the autoregulatory insert modulates intraprotein electron transfer in
      rat neuronal nitric oxide synthase.
AB  - Comparative CO photolysis kinetics studies on wild-type and autoregulatory (AR)
      insert-deletion mutant of rat nNOS holoenzyme were conducted to directly
      investigate the role of the unique AR insert in the catalytically significant FMN
      heme intraprotein electron transfer (IET). Although the amplitude of the IET
      kinetic traces was decreased two- to three-fold, the AR deletion did not change
      the rate constant for the calmodulin-controlled IET. This suggests that the rate
      limiting conversion of the electron-accepting state to a new electron-donating
      (output) state does not involve interactions with the AR insert, but that AR may
      stabilize the output state once it is formed.

PMID- 18625231
TI  - Amplification of an RNA ligase ribozyme under alternating temperature conditions.
AB  - Amplification of an RNA template molecule was examined using the ligase ribozyme
      and its corresponding RNA substrates under alternating temperature conditions.
      Alternating temperatures enhanced the rate of the thermodynamically unfavorable
      dissociation of the annealed products into the two separate RNA templates,
      reminiscent of the polymerase chain reaction. Under these conditions, the RNA
      ligase ribozyme system was observed to amplify through a mainly cross-catalytic
      process, generating additional copies of the starting RNA template molecules.
      Thus, template-directed RNA ligation using the ribozyme under thermally
      fluctuating conditions will be an intriguing point to consider when explaining
      the primordial event of chemical evolution.

PMID- 18625232
TI  - A unique residue in rab3c determines the interaction with novel binding protein
      Zwint-1.
AB  - Exocytic events are tightly regulated cellular processes in which rab GTPases and
      their interacting proteins perform an important function. We set out to identify
      new binding partners of rab3, which mediates regulated secretion events in
      specialized cells. We discovered Zwint-1 as a rab3 specific binding protein that
      bound preferentially to rab3c. The interaction depends on a critical residue in
      rab3c that determines the binding efficiency of Zwint-1, which is immaterial for
      interaction with rabphilin3a. Rab3c and Zwint-1 are expressed highly in brain and
      colocalized extensively in primary hippocampal neurons. We also found that SNAP25
      bound to the same region in Zwint-1 as rab3c, suggesting a new role for the
      kinetochore protein Zwint-1 in presynaptic events that are regulated by rab3 and
      SNAP25.

PMID- 18625233
TI  - The roles of plant dsRNA-binding proteins in RNAi-like pathways.
AB  - Dicers are associated with double-stranded RNA-binding proteins (dsRBPs) in
      animals. In the plant, Arabidopsis, there are four dicer-like (DCL) proteins and
      five potential dsRBPs. These DCLs act redundantly and hierarchically. However, we
      show there is little or no redundancy or hierarchy amongst the DRBs in their DCL
      interactions. DCL1 operates exclusively with DRB1 to produce micro (mi)RNAs, DCL4
      operates exclusively with DRB4 to produce trans-acting (ta) siRNAs and 21nt
      siRNAs from viral RNA. DCL2 and DCL3 produce viral siRNAs without requiring
      assistance from any dsRBP. DRB2, DRB3 and DRB5 appear unnecessary for mi-, tasi-,
      viral si-, or heterochromatinising siRNA production but act redundantly in a
      developmental pathway.

PMID- 18625234
TI  - N-terminal acetylation in paenibacillin, a novel lantibiotic.
AB  - N-terminal acetylation was uncovered in paenibacillin, a novel lantibiotic
      recently reported as a product of Paenibacillus polymyxa OSY-DF. This N-terminal
      modification is unprecedented among bacteria-derived antimicrobial peptides and
      further illustrates the broad range of modifications that can occur in
      lantibiotics. Additionally, the primary structure of paenibacillin has been
      finally determined unequivocally by the extensive NMR analysis taken together
      with previous MS/MS results. These analyses revealed the structure of
      paenibacillin as one of the most post-translationally modified lantibiotics.

PMID- 18625235
TI  - Dominance, aggression and physiological stress in wild male Assamese macaques
      (Macaca assamensis).
AB  - In group-living animals relative rank positions are often associated with
      differences in glucocorticoid output. During phases of social stability, when
      dominance positions are clear and unchallenged, subordinates often face higher
      costs in terms of social stress than dominant individuals. In this study we test
      this prediction and examine additional potential correlates of stress, such as
      reproductive season, age and amount of aggression received in wild, seasonally
      breeding Assamese macaques (Macaca assamensis). During a mating and a non-mating
      season we collected 394 h of focal observational data and 440 fecal samples of
      six adult and six large subadult males living in a multimale-multifemale group in
      their natural habitat in northeastern Thailand. The mating season was
      characterized by a general increase in aggressive behavior and glucocorticoid
      excretion across all males compared to the non-mating season. Among adult males,
      mating season glucocorticoid levels were significantly negatively related with
      dominance rank and positively with the amount of aggression received. Both
      relationships were non-significant among large subadult males. Thus, our results
      suggest that in adult Assamese macaques a high dominance position is not
      associated with high costs. Low costs of dominance might be induced by strong
      social bonds among top-ranking males, which exchange frequent affiliative
      interactions and serve as allies in coalitionary aggression against potentially
      rank-challenging subordinate males.

PMID- 18625236
TI  - Electrophysiological responses from neurons of antennal taste sensilla in the
      polyphagous predatory ground beetle Pterostichus oblongopunctatus (Fabricius
      1787) to plant sugars and amino acids.
AB  - The responses of antennal contact chemoreceptors, in the polyphagous predatory
      ground beetle Pterostichus oblongopunctatus, to twelve 1-1,000 mmol l(-1) plant
      sugars and seven 10-100 mmol l(-1) amino acids were tested. The disaccharides
      with an alpha-1.4-glycoside linkage, sucrose and maltose, were the two most
      stimulatory sugars for the sugar-sensitive neuron innervating these contact
      chemosensilla. The firing rates they evoked were concentration dependent and
      reached up to 70 impulses/s at 1,000 mmol l(-1). The stimulatory effect of
      glucose on this neuron was approximately two times lower. This can be partly
      explained by the fact that glucose exists in at least two anomeric forms, alpha
      and beta. These two forms interconvert over a timescale of hours in aqueous
      solution, to a final stable ratio of alpha:beta 36:64, in a process called
      mutarotation. So the physiologically active alpha-anomere forms only 36% of the
      glucose solution which was reflected in its relatively low dose/response curve.
      Due to the partial herbivory of P. oblongopunctatus these plant sugars are
      probably involved in its search for food, for example, for conifer seeds. Several
      carbohydrates, in addition to glucose, such as cellobiose, arabinose, xylose,
      mannose, rhamnose and galactose are known as components of cellulose and
      hemicelluloses. They are released by brown-rot fungi during enzymatic wood decay.
      None of them stimulated the antennal sugar-sensitive neuron. They are therefore
      not implicated in the search for hibernation sites, which include rotting wood,
      by this beetle. The weak stimulating effect (below 3 impulses/s) of some 100 mmol
      l(-1) amino acids (methionine, serine, alanine, glutamine) to the 4th
      chemosensory neuron of these sensilla was characterized as non-specific, or
      modulating the responses of non-target chemosensory neurons.

PMID- 18625237
TI  - Quantifying the structural requirements of the folding transition state of
      protein A and other systems.
AB  - The B-domain of protein A is a small three-helix bundle that has been the subject
      of considerable experimental and theoretical investigation. Nevertheless, a
      unified view of the structure of the transition-state ensemble (TSE) is still
      lacking. To characterize the TSE of this surprisingly challenging protein, we
      apply a combination of psi analysis (which probes the role of specific side-chain
      to side-chain contacts) and kinetic H/D amide isotope effects (which measures
      hydrogen-bond content), building upon previous studies using mutational phi
      analysis (which probes the energetic influence of side-chain substitutions). The
      second helix is folded in the TSE, while helix formation appears just at the
      carboxy and amino termini of the first and third helices, respectively. The
      experimental data suggest a homogenous yet plastic TS with a native-like
      topology. This study generalizes our earlier conclusion, based on two larger
      alpha/beta proteins, that the TSEs of most small proteins achieve approximately
      70% of their native state's relative contact order. This high percentage limits
      the degree of possible TS heterogeneity and requires a reevaluation of the
      structural content of the TSE of other proteins, especially when they are
      characterized as small or polarized.

PMID- 18625239
TI  - The crystal structure of UMP kinase from Bacillus anthracis (BA1797) reveals an
      allosteric nucleotide-binding site.
AB  - Uridine monophosphate (UMP) kinase is a conserved enzyme that catalyzes the ATP
      driven conversion of uridylate monophosphate into uridylate diphosphate, an
      essential metabolic step. In prokaryotes, the enzyme exists as a homohexamer that
      is regulated by various metabolites. Whereas the enzymatic mechanism of UMP
      kinase (UK) is well-characterized, the molecular basis of its regulation remains
      poorly understood. Here we report the crystal structure of UK from Bacillus
      anthracis (BA1797) in complex with ATP at 2.82 A resolution. It reveals that the
      cofactor, in addition to binding in the active sites, also interacts with
      separate binding pockets located near the center of the hexameric structure. The
      existence of such an allosteric binding site had been predicted by biochemical
      studies, but it was not identified in previous crystal structures of prokaryotic
      UKs. We show that this putative allosteric pocket is conserved across different
      bacterial species, suggesting that it is a feature common to bacterial UKs, and
      we present a structural model for the allosteric regulation of this enzyme.

PMID- 18625240
TI  - Conservation of transition state structure in fast folding peripheral subunit
      binding domains.
AB  - Phi-value analysis was used to characterise the structure of the transition state
      (TS) for folding of POB L146A Y166W, a peripheral subunit-binding domain that
      folds in microseconds. Helix 2 was structured in the TS with consolidating
      interactions from the structured loop that connects the two alpha-helices. This
      distribution of Phi-values was very similar to that determined for E3BD F166W, a
      homologue with high sequence and structural similarity. The extrapolated folding
      rate constants in water at 298 K were 210,000 s(-1) for POB and 27,500 s(-1) for
      E3BD. A contribution to the faster folding of POB came from its having
      significantly greater helical propensity in helix 2, the folding nucleus. The
      folding rate also appeared to be influenced by differences in the sequence and
      structural properties of the loop connecting the two helices. Unimodal downhill
      folding has been proposed as a conserved, biologically important property of
      peripheral subunit-binding domains. POB folds five times faster and E3BD folds
      slower than a proposed limit of 40,000 s(-1) for barrier-limited folding.
      However, experimental evidence strongly suggests that both POB L146A Y166W and
      E3BD F166W fold in a barrier-limited process through a very similar TS ensemble.

PMID- 18625238
TI  - The crystal structure of CHIR-AB1: a primordial avian classical Fc receptor.
AB  - CHIR-AB1 is a newly identified avian immunoglobulin (Ig) receptor that includes
      both activating and inhibitory motifs and was therefore classified as a
      potentially bifunctional receptor. Recently, CHIR-AB1 was shown to bind the Fc
      region of chicken IgY and to induce calcium mobilization via association with the
      common gamma-chain, a subunit that transmits signals upon ligation of many
      different immunoreceptors. Here we describe the 1.8-A-resolution crystal
      structure of the CHIR-AB1 ectodomain. The receptor ectodomain consists of a
      single C2-type Ig domain resembling the Ig-like domains found in mammalian Fc
      receptors such as FcgammaRs and FcalphaRI. Unlike these receptors and other
      monomeric Ig superfamily members, CHIR-AB1 crystallized as a 2-fold symmetrical
      homodimer that bears no resemblance to variable or constant region dimers in an
      antibody. Analytical ultracentrifugation demonstrated that CHIR-AB1 exists as a
      mixture of monomers and dimers in solution, and equilibrium gel filtration
      revealed a 2:1 receptor/ligand binding stoichiometry. Measurement of the 1:1 CHIR
      AB1/IgY interaction affinity indicates a relatively low affinity complex, but a
      2:1 CHIR-AB1/IgY interaction allows an increase in apparent affinity due to
      avidity effects when the receptor is tethered to a surface. Taken together, these
      results add to the structural understanding of Fc receptors and their functional
      mechanisms.

PMID- 18625241
TI  - The presence of a C-1/G+73 pair in a tRNA precursor influences processing and
      expression in vivo.
AB  - To understand whether 5' and 3' structural elements of the region corresponding
      to the mature tRNA affect the expression of the tRNA, we examined several
      bacterial genomes for tRNA genes where the expression might be potentially
      affected by structural elements located outside of the mature tRNA. In
      Pseudomonas aeruginosa, our analysis suggested that the tRNA(Trp) is transcribed
      together with a putative stem-loop structure followed by a uridine tract
      immediately downstream of the tRNA region. This structural element, resembling a
      Rho-independent transcription terminator, might therefore influence the
      expression and processing of tRNA(Trp). Moreover, the secondary structure
      suggested that the discriminator base in the tRNA(Trp) precursor can pair with
      either the C at position -1, the 3' terminal residue in the 5' leader, or the C
      immediately 5' of the uridine tract of the putative Rho-independent transcription
      terminator. Here, we present in vivo data demonstrating the importance of residue
      -1 and the positioning of the putative transcription terminator for the
      expression of correctly 5' processed P. aeruginosa tRNA(Trp) in Escherichia coli.
      Interestingly, we also detected a difference in the appearance of correctly 5'
      processed P. aeruginosa tRNA(Trp) in E. coli compared to the situation in P.
      aeruginosa.

PMID- 18625242
TI  - Arabidopsis thaliana glutamate receptor ion channel function demonstrated by ion
      pore transplantation.
AB  - Ionotropic glutamate receptors (iGluRs) are ligand-gated cation channels that
      mediate fast excitatory neurotransmission in the mammalian central nervous
      system. In the model plant Arabidopsis thaliana, a large family of 20 genes
      encoding proteins that share similarities with animal iGluRs in sequence and
      predicted secondary structure has been discovered. Members of this family, termed
      AtGLRs (A. thaliana glutamate receptors), have been implicated in root
      development, ion transport, and several metabolic and signalling pathways.
      However, there is still no direct proof of ligand-gated ion channel function of
      any AtGLR subunit. We used a domain transplantation technique to directly test
      whether the putative ion pore domains of AtGLRs can conduct ions. To this end, we
      transplanted the ion pore domains of 17 AtGLR subunits into rat alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate (GluR1) and kainate (GluR6) receptor
      subunits and tested the resulting chimaeras for ion channel function in the
      Xenopus oocyte expression system. We show that AtGLR1.1 and AtGLR1.4 have
      functional Na(+)-, K(+)-, and Ca(2+)-permeable ion pore domains. The properties
      of currents through the AtGLR1.1 ion pore match those of glutamate-activated
      currents, depolarisations, and glutamate-triggered Ca(2+) influxes observed in
      plant cells. We conclude that some AtGLRs have functional non-selective cation
      pores.

PMID- 18625243
TI  - Subnanometer-resolution structures of the grass carp reovirus core and virion.
AB  - Grass carp reovirus (GCRV) is a member of the Aquareovirus genus of the family
      Reoviridae, a large family of double-stranded RNA (dsRNA) viruses infecting
      plants, insects, fishes and mammals. We report the first subnanometer-resolution
      three-dimensional structures of both GCRV core and virion by cryoelectron
      microscopy. These structures have allowed the delineation of interactions among
      the over 1000 molecules in this enormous macromolecular machine and a detailed
      comparison with other dsRNA viruses at the secondary-structure level. The GCRV
      core structure shows that the inner proteins have strong structural similarities
      with those of orthoreoviruses even at the level of secondary-structure elements,
      indicating that the structures involved in viral dsRNA interaction and
      transcription are highly conserved. In contrast, the level of similarity in
      structures decreases in the proteins situated in the outer layers of the virion.
      The proteins involved in host recognition and attachment exhibit the least
      similarities to other members of Reoviridae. Furthermore, in GCRV, the RNA
      translocating turrets are in an open state and lack a counterpart for the sigma1
      protein situated on top of the close turrets observed in mammalian orthoreovirus.
      Interestingly, the distribution and the organization of GCRV core proteins
      resemble those of the cytoplasmic polyhedrosis virus, a cypovirus and the
      structurally simplest member of the Reoviridae family. Our results suggest that
      GCRV occupies a unique structure niche between the simpler cypoviruses and the
      considerably more complex mammalian orthoreovirus, thus providing an important
      model for understanding the structural and functional conservation and diversity
      of this enormous family of dsRNA viruses.

PMID- 18625244
TI  - The role of alphoid higher order repeats (HORs) in the centromere folding.
AB  - Understanding the folding of centromere DNA in the maximally condensed methaphase
      chromosome remains a basic challenge in cell biology. We propose here a set of
      structural models with a graphical presentation of alphoid higher order repeat
      (HOR) distribution in the centromere folding, based on the assumption of
      encryption key for microtubule-centromere interaction which arises from
      chromosome-specific crystal-like structure of HORs. Specific HOR leads to a
      characteristic geometrical pattern which may be responsible for individual
      microtubule to recognize a specific structure of centromere in each chromosome.

PMID- 18625245
TI  - Should females prefer to mate with low-quality males?
AB  - We analyse a model of mate choice when males differ in reproductive quality and
      provide care for their offspring. Females choose males on the basis of the
      success they will obtain from breeding with them and a male chooses his care time
      on the basis of his quality so as to maximise his long-term rate of reproductive
      success. We use this model to establish whether high-quality males should devote
      a longer period of care to their broods than low-quality males and whether
      females obtain greater reproductive success from mating with higher quality
      males. We give sufficient conditions for optimal care times to decrease with
      increasing male quality. When care times decrease, this does not necessarily mean
      that high-quality males are less valuable to the female because quality may more
      than compensate for the lack of care. We give a necessary and sufficient
      condition for high-quality males to be less valuable mates, and hence for females
      to prefer low-quality males. Females can prefer low-quality males if offspring
      produced and cared for by high-quality males do well even if care is short, and
      do not significantly benefit from additional care, while offspring produced and
      cared for by low-quality males do well only if they receive a long period of
      care.

PMID- 18625246
TI  - One-third rules with equality: Second-order evolutionary stability conditions in
      finite populations.
AB  - The one-third law of evolutionary dynamics [Nowak et al. 2004. Emergence of
      cooperation and evolutionary stability in finite populations. Nature 428, 246
      650] describes a robustness criterion for evolution in a finite population: If at
      an A-frequency of 1/3, the fitness of an A player is greater (smaller) than the
      fitness of a B player, then a single A mutant that appears in a population of
      otherwise all B has a fixation probability greater (smaller) than the neutral
      threshold 1/N, the inverse population size. We examine the case where at an A
      frequency of 1/3, the fitness of an A player is exactly equal to the fitness of a
      B player. We find that in this case the relative magnitude of the cross payoffs
      matters: If the payoff of A against B is larger (smaller) than the payoff of B
      against A, then a single A mutant has a fixation probability larger (smaller)
      than 1/N. If the cross payoffs coincide, we are in the special case of a
      partnership game, where the deviation cost from an inefficient equilibrium is
      exactly balanced by the potential gain of switching to the payoff dominant
      equilibrium. We show that in this case the fixation probability of A is lower
      than 1/N. Finally, we illustrate our findings by a language game with
      differentiated costs of signals.

PMID- 18625247
TI  - On the role of bone damage in calcium homeostasis.
AB  - Bone serves as the reservoir of some minerals including calcium. If calcium is
      needed anywhere in the body, it can be removed from the bone matrix by resorption
      and put back into the blood flow. During bone remodelling the resorbed tissue is
      replaced by osteoid which gets mineralized very slowly. Then, calcium homeostasis
      is controlled by bone remodelling, among other processes: the more intense is the
      remodelling activity, the lower is the mineral content of bone matrix. Bone
      remodelling is initiated by the presence of microstructural damage. Some
      experimental evidences show that the fatigue properties of bone are degraded and
      more microdamage is accumulated due to the external load as the mineral content
      increases. That damage initiates bone remodelling and the mineral content is so
      reduced. Therefore, this process prevents the mineral content of bone matrix to
      reach very high (non-physiological) values. A bone remodelling model has been
      used to simulate this regulatory process. In this model, damage is an initiation
      factor for bone remodelling and is estimated through a fatigue algorithm,
      depending on the macroscopic strain level. Mineral content depends on bone
      remodelling and mineralization rate. Finally, the bone fatigue properties are
      defined as dependent on the mineral content, closing the interconnection between
      damage and mineral content. The remodelling model was applied to a simplified
      example consisting of a bar under tension with an initially heterogeneous mineral
      distribution. Considering the fatigue properties as dependent on the mineral
      content, the mineral distribution tends to be homogeneous with an ash fraction
      within the physiological range. If such dependance is not considered and fatigue
      properties are assumed constant, the homogenization is not always achieved and
      the mineral content may rise up to high non-physiological values. Thus, the
      interconnection between mineral content and fatigue properties is essential for
      the maintenance of bone's structural integrity as well as for the calcium
      homeostasis.

PMID- 18625248
TI  - The positive inotropic effect of endothelin-1 is mediated by mitochondrial
      reactive oxygen species.
AB  - We have previously demonstrated the participation of reactive oxygen species
      (ROS) in the positive inotropic effect of a physiological concentration of
      Angiotensin II (Ang II, 1 nM). The objective of the present work was to evaluate
      the role and source of ROS generation in the positive inotropic effect produced
      by an equipotent concentration of endothelin-1 (ET-1, 0.4 nM). Isolated cat
      ventricular myocytes were used to measure sarcomere shortening with a video
      camera, superoxide anion (()O(2)(-)) with chemiluminescence, and ROS production
      and intracellular pH (pH(i)) with epifluorescence. The ET-1-induced positive
      inotropic effect (40.4+/-3.1%, n=10, p<0.05) was associated to an increase in ROS
      production (105+/-29 fluorescence units above control, n=6, p<0.05). ET-1 also
      induced an increase in ()O(2)(-) production that was inhibited by the NADPH
      oxidase blocker, apocynin, and by the blockers of mitochondrial ATP-sensitive
      K(+) channels (mK(ATP)), glibenclamide and 5 hydroxydecanoic acid. The ET-1
      induced positive inotropic effect was inhibited by apocynin (0.3 mM; 6.3+/-6.6%,
      n=13), glibenclamide (50 microM; 8.8+/-3.5%, n=6), 5 hydroxydecanoic acid (500
      microM; 14.1+/-8.1, n=9), and by scavenging ROS with MPG (2 mM; 0.92+/-5.6%,
      n=8). ET-1 enhanced proton efflux (J(H)) carried by the Na(+)/H(+) exchanger
      (NHE) after an acid load, effect that was blocked by MPG. Consistently, the ET
      induced positive inotropic effect was also inhibited by the NHE selective blocker
      HOE642 (5 microM; 9.37+/-6.07%, n=7). The data show that the effect of a
      concentration of ET-1 that induces an increase in contractility of about 40% is
      totally mediated by an intracellular pathway triggered by mitochondrial ROS
      formation and stimulation of the NHE.

PMID- 18625249
TI  - Differential metabolism of 4-n- and 4-tert-octylphenols in perfused rat liver.
AB  - Octylphenols, widely used in a variety of detergents and plastics, are known to
      exhibit estrogenicity in vivo. The details of their metabolism are needed to
      better understand the endocrine disruptions. We have previously shown that
      alkylphenols, having short alkyl chains, are glucuronidated and readily excreted
      into the bile from the liver, while 4-n-nonylphenol, having longer alkyl chains,
      remains as the alkylphenol's glucuronide in the tissue. This study elucidated the
      dependence of the metabolism on the shape of the alkyl chains by comparing 4-n
      octylphenol and 4-tert-octylphenols in a perfused rat liver. Both octylphenols
      were highly glucuronidated by the liver microsomal fractions. The Vmax value of 4
      tert-octylphenol glucuronidation was twice as high as that of 4-n-octylphenol in
      the liver microsomes. On the other hand, the Km values, being measures of
      enzymatic activity against these chemicals, were similar. 4-n-Octylphenol and 4
      tert-octylphenol were both glucuronidated by a UDP-glucuronosyltransferase
      isoform, UGT2B1, expressed in the liver. In the liver perfusion, almost all of
      the 4-n-octylphenol perfused was metabolized directly to the glucuronide, whereas
      a portion of 4-tert-octylphenol was hydroxylated and then glucuronidated. The
      glucuronide of 4-n-octylphenol accumulated in the liver tissue in the same manner
      as 4-n-nonylphenol, but 4-tert-octylphenol and the hydroxylated metabolites were
      excreted readily into the bile. Only a small amount of 4-n-octylphenol
      glucuronide and glucuronides of 4-tert-octylphenol and its hydroxylated
      metabolites could be excreted into the bile of Eisai hyperbilirubinemic rats
      (EHBR). These animals are deficient in xenobiotic conjugate transporter,
      multidrug resistance-associated protein (MRP-2), indicating that the glucuronides
      of both octylphenols are transported by MRP-2. These results indicate that the
      differences in metabolism of these octylphenols are due to the shape of their
      alkyl chains, suggesting that the estrogenic activities of not only the parent
      chemicals but also these metabolites must be taken into consideration.

PMID- 18625250
TI  - Pharmacological properties of P2 receptors on rat otic parasympathetic ganglion
      neurons.
AB  - To elucidate the pharmacological profile of P2X receptors and the probable
      expression of P2Y receptors in otic ganglion neurons from 17-day-old rats, single
      neurons were enzymatically isolated and maintained in tissue culture for up to 30
      h. Whole-cell voltage-clamp recording was carried out at a holding potential of 
      60 mV. Most otic ganglion neurons responded to adenosine 5'-triphosphate (ATP), 2
      methylthio ATP (2-MeSATP) and alpha,beta-methylene ATP (alphabeta-meATP) with
      sustained currents and EC(50) values of 19 microM, 47 microM and 94 microM,
      respectively. 2',3'-O-trinitrophenyl-ATP (TNP-ATP) inhibited the response to
      alphabeta-meATP and ATP with an IC(50) values of 3.9 nM and 18.3 nM,
      respectively, which was closed to that observed in nodose neurons. The response
      to ATP was antagonized by suramin and cibacron blue. The dose-response curve of
      suramin against ATP response at a pH of 6.5 was shifted to the left compared to
      that at a pH of 7.4. Diinosine pentaphosphate (Ip(5)I), which blocks P2X(3), but
      not P2X(2/3)-mediated responses, had no effect on the currents evoked by ATP or
      alphabeta-meATP. In some neurons, uridine 5'-triphosphate (UTP) induced a tiny,
      but long-lasting current with a mean amplitude of 0.034+/-0.011 nA. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) confirmed the expression of
      mRNAs for P2X(2), P2X(3), P2X(4), P2X(6) and P2X(7), but not for P2X(1) and
      P2X(5) receptors in otic ganglion. In conclusion, in rat otic ganglion neurons,
      P2X(2/3) heteromultimer receptors dominate, but P2X(7) and P2Y(2) or P2Y(4)
      receptors also play roles.

PMID- 18625251
TI  - Penn/VA center for studies of addiction.
AB  - The Penn/VA Center was founded in 1971 because of great concern over the number
      of Vietnam veterans returning home addicted to heroin. At that time little was
      known about the science of addiction, so our program from the very beginning was
      designed to gather data about the nature of addiction and measure the effects of
      available treatments. In other words, the goals were always a combination of
      treatment and research. This combination has continued to the present day. A
      human laboratory for the study of addiction phenomena such as conditioned
      responses was also founded in 1971. The key clinician investigators in this group
      have remained in the Center since the 1970s with most of the research staff
      continuing to work together. Important new investigators have been added over the
      years. Treatment was empirically based with randomized, controlled clinical
      trials as the gold standard for determining evidence-based treatment. The
      patients coming to treatment do not distinguish between abuse of alcohol and
      other drugs, so the treatment and research programs have always focused on all
      drugs including ethyl alcohol and the combination of ethyl alcohol with other
      drugs such as cocaine and opioids. Most of the patients coming for treatment also
      suffered from additional psychiatric disorders such as depression, anxiety,
      bipolar disorder or schizophrenia. Thus, the addiction treatment program in 1980
      absorbed the rest of the VA Psychiatry Service into the Substance Abuse Program
      forming a new Behavioral Health Service with responsibility for over 9000
      patients. The integration of substance abuse treatment with overall mental health
      care was the most efficient way to handle patients with complicated combinations
      of disorders. While this continues to be the best way to treat patients, it has
      proven difficult in practice. The main reason for this difficulty is that most
      mental health therapists whether they are psychiatrists, psychologists or social
      workers feel very inadequate to handle substance abuse problems. Unless they have
      had specialized training in addictive disorders, therapists are likely to be
      uncomfortable if substance abuse is one of the diagnoses while they may be quite
      comfortable treating other complex disorders such as schizophrenia. This lack of
      education of clinicians remains a major problem for our field. Some of the
      findings that came out of both the Penn/VA laboratory and clinical studies are
      now widely accepted and form the basis of standard clinical practice. These
      concepts and evidence will be briefly reviewed below.

PMID- 18625252
TI  - Special issue on cerebral ischemia. Foreword.

PMID- 18625254
TI  - Metabotropic glutamate receptors mGluR4 and mGluR8 regulate transmission in the
      lateral olfactory tract-piriform cortex synapse.
AB  - The piriform cortex (PC) is the primary terminal zone of projections from the
      olfactory bulb, termed the lateral olfactory tract (LOT). The PC plays a critical
      role in processing of olfactory stimuli and is also a highly seizure prone area
      thought to be involved in some forms of temporal lobe epilepsy. Pharmacological
      and immunohistochemical studies provide evidence for the localization of various
      metabotropic glutamate receptors (GluRs) in the PC. We employed whole-cell patch
      clamp recordings from PC pyramidal cells to determine the roles of group III
      mGluRs in modulating synaptic transmission at the LOT-PC synapse. The group III
      mGluR agonist, L-AP4, induced a concentration-dependent inhibition of synaptic
      transmission at the LOT-PC synapse at concentrations that activate mGluR4 and
      mGluR8, but not mGluR7 or other mGluR subtypes (EC50=473nM). In addition, the
      selective mGluR8 agonist, DCPG (300nM), also suppressed synaptic transmission at
      the LOT synapse. Furthermore, the inhibitory actions of L-AP4 and Z-cyclopentyl
      AP4, a selective mGluR4 agonist, were potentiated by the mGluR4 positive
      allosteric modulator, PHCCC (30microM). The high potency of L-AP4, combined with
      the observed effects of DCPG and PHCCC, suggests that both mGluR4 and mGluR8 play
      a role in the l-AP4-induced inhibition of synaptic transmission at the LOT-PC
      synapse.

PMID- 18625253
TI  - Dissecting motivational circuitry to understand substance abuse.
AB  - An important goal of cocaine addiction research is to understand the
      neurobiological mechanisms underlying this disease state. Here, we review studies
      from our laboratory that examined nucleus accumbens (NAc) cell firing and rapid
      dopamine signaling using electrophysiological and electrochemical recordings in
      behaving rodents. A major advantage of these techniques is that they allow for
      the characterization of NAc activity and rapid dopamine release during specific
      phases of motivated behavior. Moreover, each approach enables an examination of
      the dynamic nature of NAc signaling as a function of factors such as hedonics and
      associative learning. We show that NAc neurons differentially respond to
      rewarding and aversive stimuli and their predictors in a bivalent manner. This
      differential responding is modifiable and can be altered by the presentation of
      other natural rewards or cocaine. Likewise, the dynamic nature of NAc cell firing
      is also reflected in the differential activation of distinct populations of NAc
      neurons during goal-directed behaviors for natural versus drug rewards, and the
      heightened activation of some NAc neurons following cocaine abstinence. Our
      electrochemical data also show that rapid dopamine signaling in the NAc reflects
      primary rewards and their predictors and appears to modulate specific NAc
      neuronal responses. In some cases, these influences are observed in a regionally
      specific manner that matches previous pharmacological manipulations.
      Collectively, these findings provide critical insight into the functional
      organization of the NAc that can be used to guide additional studies aimed at
      dissecting the neural code underlying compulsive drug-seeking behavior.

PMID- 18625255
TI  - Presynaptic mGlu1 and mGlu5 autoreceptors facilitate glutamate exocytosis from
      mouse cortical nerve endings.
AB  - The effects of mGlu1 and mGlu5 receptor activation on the depolarization-evoked
      release of [3H]d-aspartate ([3H]D-ASP) from mouse cortical synaptosomes were
      investigated. The mGlu1/5 receptor agonist 3,5-DHPG (0.1-100microM) potentiated
      the K+(12mM)-evoked [3H]D-ASP overflow. The potentiation occurred in a
      concentration-dependent manner showing a biphasic pattern. The agonist
      potentiated [3H]D-ASP exocytosis when applied at 0.3microM; the efficacy of 3,5
      DHPG then rapidly declined and reappeared at 30-100microM. The fall of efficacy
      of agonist at intermediate concentration may be consistent with 3,5-DHPG-induced
      receptor desensitization. Facilitation of [3H]D-ASP exocytosis caused by
      0.3microM 3,5-DHPG was prevented by the selective mGlu5 receptor antagonist MPEP,
      but was insensitive to the selective mGlu1 receptor antagonist CPCCOEt. In
      contrast, CPCCOEt prevented the potentiation by 50microM 3,5-DHPG, while MPEP had
      minimal effect. Unexpectedly, LY 367385 antagonized both the 3,5-DHPG-induced
      effects. A total of 0.3microM 3,5-DHPG failed to facilitate the K+-evoked [3H]D
      ASP overflow from mGlu5 receptor knockout (mGlu5-/-) cortical synaptosomes, but
      not from nerve terminals prepared from the cortex of animals lacking the mGlu1
      receptors, the crv4/crv4 mice. On the contrary, 50microM 3,5-DHPG failed to
      affect the [3H]D-ASP exocytosis from cortical synaptosomes obtained from
      crv4/crv4 and mGlu5-/-mice. Western blot analyses in subsynaptic fractions
      support the existence of both mGlu1 and mGlu5 autoreceptors located
      presynaptically, while immunocytochemistry revealed their presence at
      glutamatergic terminals. We propose that mGlu1 and mGlu5 autoreceptors exist on
      mouse glutamatergic cortical terminals; mGlu5 receptors may represent the "high
      affinity" binding sites for 3,5-DHPG, while mGlu1 autoreceptors represent the
      "low affinity" binding sites.

PMID- 18625257
TI  - Functional interaction between adenosine A2A and group III metabotropic glutamate
      receptors to reduce parkinsonian symptoms in rats.
AB  - Non-dopaminergic drugs acting either on adenosine A2A or metabotropic glutamate
      (mGlu) receptors reduce motor impairment in animal models of Parkinson's disease
      (PD), suggesting a possible functional interaction between these receptors to
      regulate basal ganglia function. The present study therefore tested the
      behavioural effects of compounds acting selectively on A2A or on specific mGlu
      receptor subtypes, alone or in combination, in rodent models of PD. Acute
      administration of the adenosine A2A receptor antagonists CSC or MSX-3 at the
      highest doses tested (5 and 1.25mg/kg, respectively) significantly reduces
      haloperidol-induced catalepsy. Furthermore, the anticataleptic effect of MSX-3
      was enhanced by a 3-week treatment. Acute administration of the selective group
      III mGlu agonist ACPT-I produces potent anticataleptic effects and prolongs time
      on rotarod of 6-OHDA-lesioned rats. In contrast, acute or chronic administration
      of MPEP (mGlu5 receptor antagonist) has no anticataleptic action. Furthermore,
      the acute co-administration of ACPT-I 1mg/kg, but not 5mg/kg, with CSC markedly
      reduces catalepsy. Opposite effects are observed after a 3-week co
      administration. The co-administration of ACPT-I with MSX-3 has anticataleptic
      effects both after acute or chronic treatment. In contrast, acute combination of
      subthreshold doses of CSC and MPEP has no effect. After a 3-week treatment,
      however, the combination of CSC and MPEP was found to reduce haloperidol-induced
      catalepsy. Altogether, these results show for the first time that systemic
      activation of group III mGlu receptors with ACPT-I provides benefits in
      parkinsonian rats and underlie a possible interaction with A2A receptors to
      regulate basal ganglia motor function.

PMID- 18625256
TI  - Desipramine potentiation of the acute depressant effects of ethanol: modulation
      by alpha2-adrenoreceptors and stress.
AB  - Ethanol exerts effects on the brain noradrenergic system, and these are thought
      to contribute to the sedative/hypnotic (depressant) effects of ethanol. Recent
      studies suggest that the norepinephrine transporter (NET) plays an important role
      in modulating ethanol's depressant effects. The aim of the present study was to
      further characterize this role. Transporter blockers with varying affinity for
      NET versus the serotonin transporter (desipramine>fluoxetine>citalopram) were
      tested for their ability to alter ethanol's depressant effects, and for
      comparison, hypothermic effects. Effects of desipramine on another depressant,
      pentobarbital, were examined. Desipramine potentiation of ethanol's depressant
      effects was assessed following depletion of brain norepinephrine via N-(2
      chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) treatment, or
      depletion of brain 5-HT via para-chlorophenylalanine methyl ester hydrochloride
      (PCPA) treatment. The effects of co-administration of either the selective alpha2
      adrenoreceptor agonist (dexmedetomidine) or the selective alpha2-adrenoreceptor
      antagonist (atipamezole) on desipramine's effect on ethanol's depressant effects
      were examined. Given the close link between stress, ethanol and norepinephrine,
      desipramine potentiation of ethanol's depressant effects was tested following
      repeated forced swim stress. Results showed that desipramine, but not SERT
      selective doses of citalopram or fluoxetine, strongly potentiated the depressant
      (not hypothermic) effects of ethanol. These effects were mimicked by
      dexmedetomidine and blocked by atipamezole, but not by depletion of either
      norepinephrine or 5-HT. Desipramine potentiation of ethanol's depressant effects
      was abolished following repeated stress. Present findings further support a major
      role for NET and the alpha2-adrenoreceptor in modulating the depressant effects
      of ethanol, with possible implications for understanding the role of
      noradrenergic dysfunction in stress-related alcoholism.

PMID- 18625259
TI  - Does localisation blindsight extend to two-dimensional targets?
AB  - Residual sensorimotor skills which survive compromise of the geniculostriate
      visual system may depend on activity of the dorsal stream of extrastriate
      occipitoparietal cortex. These circuits are crucial for controlling hand and eye
      movements to targets in a three-dimensional world. Remarkably, demonstrations of
      above chance localisation by hand and by eye in blindsight patients have used
      luminous targets that were only varied in one spatial dimension. These
      limitations result in experimental confounds. In the present study we examined
      saccadic and manual localisation in a well-studied patient (DB) to positions that
      were varied in 1 or 2 dimensions, using targets which control for luminance
      artefacts. We found that his good manual localisation without awareness in 1D
      conditions was relatively preserved when the targets were varied in 2D. In stark
      contrast, saccadic performance was completely attenuated with 2D targets. These
      paradoxical results are difficult to reconcile with feedforward models of eye
      hand coordination and with accounts of localisation that depend on intact
      multidimensional representations of the visual fields in non-geniculostriate
      systems.

PMID- 18625258
TI  - Allosteric potentiators of metabotropic glutamate receptor subtype 1a
      differentially modulate independent signaling pathways in baby hamster kidney
      cells.
AB  - Recent studies suggest that subtype specific activators of metabotropic glutamate
      receptors (mGluRs) have exciting potential for the development of novel treatment
      strategies for numerous psychiatric and neurological disorders. A number of
      positive allosteric modulators (PAMs) have been identified that are highly
      selective for mGluR1, including the compounds Ro 01-6128, Ro 67-4853, and Ro 67
      7476. These PAMs have been previously found to interact with a site distinct from
      that of negative allosteric modulators (NAMs), typified by R214127. These mGluR1
      PAMs do not have an effect on baseline calcium levels but induce leftward shifts
      in the concentration-response of mGluR1 to agonists. However, their effects on a
      variety of signaling pathways and their mechanism of action have not been fully
      explored and are of critical importance for further development of mGluR1
      allosteric modulators as novel drugs. In baby hamster kidney (BHK) cells, mGluR1
      activates calcium mobilization, cAMP production, and extracellular signal
      regulated kinase 1/2 (ERK1/2) phosphorylation; signaling cascades which are
      distinct and differentially regulated. In contrast to their effects on calcium
      mobilization, these compounds were found to activate ERK1/2 phosphorylation in
      the absence of exogenously added agonist, an effect that was fully blocked by
      both orthosteric (LY341495) and allosteric (R214127) mGluR1 antagonists. The
      mGluR1 PAMs were also found to activate cAMP production in the absence of
      agonist. Thus, these mGluR1 PAMs have qualitatively different effects on a
      variety of mGluR1-mediated signal transduction cascades. Together, these data
      provide further evidence that allosteric compounds can differentially modulate
      the coupling of a single receptor to independent signaling pathways or act in a
      system-dependent manner.

PMID- 18625260
TI  - Purification and N-terminal sequence of a serine proteinase-like protein (BMK
      CBP) from the venom of the Chinese scorpion (Buthus martensii Karsch).
AB  - A serine proteinase-like protein was isolated from the venom of Chinese red
      scorpion (Buthus martensii Karsch) by combination of gel filtration, ion-exchange
      and reveres-phase chromatography and named BMK-CBP. The apparent molecular weight
      of BMK-CBP was identified as 33 kDa by SDS-PAGE under non-reducing condition. The
      sequence of N-terminal 40 amino acids was obtained by Edman degradation. The
      sequence shows highest similarity to proteinase from insect source. When tested
      with commonly used substrates of proteinase, no significant hydrolytic activity
      was observed for BMK-CBP. The purified BMK-CBP was found to bind to the cancer
      cell line MCF-7 and the cell binding ability was dose-dependent.

PMID- 18625261
TI  - Mortality due to snakebite envenomation in Costa Rica (1993-2006).
AB  - The mortality due to snakebite envenomation in Costa Rica for the period 1993
      2006 was investigated by a retrospective analysis. There were 48 fatalities due
      to snakebites during this period. Mortality rates ranged from 0.02 per 100,000
      population in 2006 to 0.19 per 100,000 population in 1993. Case fatality rates in
      the period 1993-2000 ranged between 0.18% (2000) and 1.15% (1993). The highest
      numbers of fatal cases occurred in the provinces of Puntarenas and Limon, in low
      land humid regions where the species Bothrops asper ('terciopelo') is distributed
      and agricultural activities predominate. The most affected age groups were those
      of 20-29, 40-49 and 50-59 years, and fatal cases predominated in males over
      females by a ratio of 5:1.

PMID- 18625263
TI  - Suppressive effect and mechanism of saxatilin, a disintegrin from Korean snake
      (Gloydius saxatilis), in vascular smooth muscle cells.
AB  - RGD-peptides can inhibit the binding of ligands to certain beta3 integrins,
      alphaIIbbeta3 and alphavbeta3, both of which are involved in neointimal
      hyperplasia that contributes to atherosclerosis and restenosis of arterial walls.
      Saxatilin, a disintegrin from a Korean snake (Gloydius saxatilis), interacts with
      integrins alphaIIbbeta3 and alphavbeta3. It suppressed the adhesion of human
      coronary artery smooth muscle cells (HCASMCs) to vitronectin with an IC(50) of
      2.5 microM, and growth factor (PDGF-BB or bFGF)-induced proliferation was
      inhibited at an IC(50) of 25 microM. Saxatilin disassembled the actin
      cytoskeleton of focal adhesion and induced cell detachment. This disassembly of
      focal adhesion in saxatilin-treated HCASMCs involved caspase-induced paxillin
      degradation. Saxatilin temporally phosphorylated FAK and ERKs and affected the
      cell cycle of HCASMCs by increasing CDK inhibitors (p21 and p27) and reducing
      cyclins (D1/2 and E). These results may have significant implications for
      integrin antagonistic therapy used for the treatment of atherosclerosis and
      restenosis.

PMID- 18625262
TI  - Melanoma cell growth inhibition by betagamma-CAT, which is a novel non-lens
      betagamma-crystallin and trefoil factor complex from frog Bombina maxima skin.
AB  - In vertebrates, non-lens betagamma-crystallins are widely expressed in various
      tissues but their functions are unknown. The molecular mechanisms of trefoil
      factors, initiators of mucosal healing and being greatly involved in
      tumorigenesis, have remained elusive. betagamma-CAT, which is responsible for the
      potent hemolytic activity and lethal toxicity on mice of frog Bombina maxima skin
      secretions, is the first example of a non-lens betagamma-crystallin and trefoil
      factor complex. Its alpha- and beta-subunits show significant sequence homology
      to human Absent In Melanoma 1 and trefoil factors, respectively. Here, we showed
      that betagamma-CAT triggered two types of cellular responses in human melanoma
      cells. On one hand, the protein (25-200 pM) was able to stimulate cell migration
      in melanoma A375 cells. On the other hand, it inhibited cell proliferation by
      delaying S-G2/M cell phase transition. Blockade of the cell cycle was associated
      with increased p21/WAF1 expression, and reduced amounts of Cdc2 and Cdc25C.
      betagamma-CAT also reduced Cdc2 function by increasing the level of inactivated
      phospho-Cdc2. In addition, the expression of JunB, a well-known cell
      proliferation inhibitor, was significantly up-regulated. These results provide
      the first evidence of an anti-proliferative role for a non-lens betagamma
      crystallin member and action mechanism via association with a trefoil factor.

PMID- 18625264
TI  - The neutralizing capacity of Androctonus crassicauda antivenom against Mesobuthus
      eupeus scorpion venom.
AB  - Scorpion envenomations are considerable health problem in tropical and
      subtropical regions. There are approximately 1,500 species of scorpions
      worldwide. The number of dangerous species in the Buthidae family is
      significantly higher than in other families of scorpions. Mesobuthus eupeus is a
      member of Mesobuthus genus, Buthidae family. In this study, the potency and para
      specific activities of Androctonus crassicauda antivenom were investigated
      against M. eupeus scorpion venom. The median lethal dose of M. eupeus and A.
      crassicauda scorpion venoms were found to be 0.18 mg/kg, 15.45 microg/kg by i.c.v
      injection route. The antivenom showed neutralization effect against the venoms of
      M. eupeus. One milliliter of A. crassicauda antivenom neutralizes 464LD(50) of M.
      eupeus and 940LD(50)A. crassicauda venom on mice. Western blotting demonstrated
      immunologic reaction with the venoms. The monovalent antivenom has immunoactivity
      and neutralizing capacity to the scorpion venoms. This study indicates that the
      antivenom produced by Refik Saydam Hygiene Center could be used for the treatment
      of M. eupeus stings in Turkey.

PMID- 18625265
TI  - The amblyopic deficit for global motion is spatial scale invariant.
AB  - Humans with amblyopia display anomalous performance for global motion
      discrimination. Attempts have been made to rule out an explanation based solely
      on the visibility loss in lower visual areas. However, it remains a possibility
      that the altered scale over which local motion is processed in V1 might lead to
      reduced efficiency of global motion processing in extra-striate cortex. We use
      stimuli composed of spatial frequency bandpass elements, equated for visibility,
      to show that the global motion deficit in amblyopia for both fellow and amblyopic
      eyes is still present once impairments in low-level processing have been factored
      out. This residual deficit appears to be spatial scale invariant and the relative
      deficit between the eyes shows a dependence on stimulus speed. We believe that
      this rules out an explanation of the amblyopic global motion deficit based solely
      on local motion input. We suggest instead that, in addition to low-level
      deficits, motion processing in a broadband, extra-striate, global motion
      mechanism is impaired in amblyopia.

PMID- 18625266
TI  - The effects of eccentricity and retinal illuminance on the illusory motion seen
      in a stationary luminance gradient.
AB  - Kitaoka recently reported a novel illusion named the Rotating Snakes [Kitaoka,
      A., & Ashida, H. (2003). Phenomenal characteristics of the peripheral drift
      illusion. Vision, 15, 261-262], in which a stationary pattern appears to rotate
      constantly. In the first experiment, we attempted to quantify the anecdote that
      this illusion is better perceived in the periphery. The stimulus was a ring
      composed of stepwise luminance patterns and was presented in the left visual
      field. With increasing eccentricity up to 10-14deg, the cancellation velocity
      required to establish perceptual stationarity increased. In the next experiment,
      we examined the effect of retinal illuminance. Interestingly, the cancellation
      velocity decreased as retinal illuminance was decreased. We also estimated the
      human temporal impulse response at some retinal illuminances by using the double
      pulse method to confirm that the shape of the impulse response actually changes
      from biphasic to monophasic, which indicates that the transient processing system
      has weaker activities at lower illuminances. We conclude that some transient
      temporal processing system is necessary for the illusion.

PMID- 18625267
TI  - Changes in orientation discrimination at the time of saccadic eye movements.
AB  - Perceptual performance has been known to change around the time of saccadic eye
      movement. In the current study, we measured the accuracy and sensitivity of
      orientation discrimination of bar stimuli presented during fixation and before
      saccadic eye movements. Human participants compared the orientations of the test
      and reference bar stimuli with the head erect in a two-interval forced choice
      task. For the targets presented during steady fixation, the accuracy and
      sensitivity of orientation discrimination were better near the cardinal than
      oblique axes, a perceptual anisotropy known as the oblique effect. For the
      targets presented during the 100 ms interval immediately before a saccade was
      executed, the anisotropy decreased mainly due to reduction in sensitivity for
      cardinal orientations. Directing attention to the goal location of the impending
      saccade emulated the saccadic effects on orientation discrimination for the
      targets at saccadic goal, suggesting that the saccadic effects on orientation
      discrimination are partly mediated by the shift of spatial attention that
      accompanies the saccade. These results were in line with the anti-oblique effect
      that perceptual judgment of motion direction along the oblique angle becomes
      relatively accurate for motion targets presented before saccadic eye movements
      [Lee, J., & Lee, C. (2005). Changes in visual motion perception before saccadic
      eye movements. Vision Research, 45(11), 1447-1457].

PMID- 18625268
TI  - Give food a chance: treating anorexia nervosa without drugs and psychology.
AB  - The eating disorder, anorexia nervosa, is a potentially lethal, leading cause of
      disability in young women, and a biological perspective on this important problem
      might further our understanding of the physiological control of energy balance.
      The article by Sodersten, Nergardh, Bergh, Zandian, and Scheurink describes a new
      treatment for anorexia nervosa with an impressive success rate and without
      prescription drugs or psychotherapy. Like the cause of the disease, this new
      method of treatment lacks a firm theoretical foundation based on experimental
      data. The authors' explanation for their success rate, however, is intriguing.
      This new treatment is as worthy of study as any of the others now available. I
      encourage clinicians to give this biological perspective a fair evaluation, and
      behavioral neuroendocrinologists to consider the implications for physiological
      control of ingestive and reproductive behavior.

PMID- 18625269
TI  - Selection of diverse and clinically relevant integrase inhibitor-resistant human
      immunodeficiency virus type 1 mutants.
AB  - Resistance passage studies were conducted with five INIs (integrase inhibitors)
      that have been tested in clinical trials to date: a new naphthyridinone-type INI
      S/GSK-364735, raltegravir, elvitegravir, L-870,810 and S-1360. In establishing
      the passage system and starting from concentrations several fold above the EC(50)
      value, resistance mutations against S-1360 and related diketoacid-type compounds
      could be isolated from infected MT-2 cell cultures from day 14 to 28. Q148R and
      F121Y were the two main pathways of resistance to S/GSK-364735. Q148R/K and
      N155H, which were found in patients failing raltegravir treatment in Phase IIb
      studies, were observed during passage with raltegravir with this method. The fold
      resistance of 40 mutant molecular clones versus wild type virus was compared with
      these five INIs. The overall resistance pattern of S/GSK-364735 was similar to
      that of raltegravir and other INIs. However, different fold resistances of
      particular mutations were noted among different INIs, reflecting a potential to
      develop INIs with distinctly different resistant profiles.

PMID- 18625270
TI  - Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome
      entry site (IRES) dependent translation in vitro.
AB  - The internal ribosome entry site (IRES) of hepatitis C virus (HCV) which governs
      the initiation of protein synthesis from viral RNA represents an ideal target for
      antisense approaches. Using an original bicistronic plasmid, we first established
      that sequence and translational activity of HCV IRESs cloned from six patients,
      whether responders or not to combination therapy, were conserved. We then tested
      the hypothesis that antisense molecules, i.e. short peptide nucleic acids (PNA),
      could inhibit HCV translation by binding to the highly conserved IIId or IV loop
      regions of the IRES. Five 6-10mer PNAs were designed. They strongly inhibit HCV
      IRES-driven translation in a rabbit reticulocyte lysate assay. This inhibition
      was highly specific since corresponding PNAs with only one mismatch were
      inactive. Short phosphorothioate oligonucleotides of same sequence were unable to
      inhibit HCV translation. PNA molecule was shown to have anti-HCV activity in Huh
      7.5 cells when electroporated with a full-length HCV genome construct. Using
      oligonucleotide as carrier, PNA was also transfected in HCV replicon-harboring
      cells and in JFH1 infected Huh-7.5 cells.

PMID- 18625271
TI  - Evaluation of bioemulsifier mediated Microbial Enhanced Oil Recovery using sand
      pack column.
AB  - Bacillus licheniformis K125, isolated from an oil reservoir, produces an
      effective bioemulsifier. The crude bioemulsifier showed 66% emulsification
      activity (E(24)) and reduced the surface tension of water from 72 to 34 mN/m. It
      contains substantial amount of polysaccharide, protein and lipid. This
      bioemulsifier is pseudoplastic non-Newtonian in nature. It forms oil in water
      emulsion which remains stable at wide range of pH, temperature and salinity. It
      gave 43+/-3.3% additional oil recovery upon application to a sand pack column
      designed to simulate an oil reservoir. This is 13.7% higher than that obtained
      from crude lipopeptide biosurfactants produced by the standard strain, Bacillus
      mojavensis JF2 and 8.5% higher than hot water spring isolate, Bacillus
      licheniformis TT42. The increased oil recovery obtained by using the crude
      bioemulsifier can be attributed to its combined surface and emulsification
      activity. Its mechanism of oil recovery must be similar to the mechanism
      exhibited by surfactant-polymer flooding process of chemical enhanced oil
      recovery.

PMID- 18625272
TI  - Headspace sorptive extraction and GC-TOFMS for the identification of volatile
      fungal metabolites.
AB  - Volatiles from fungi cultivated in Petri dishes were collected by a simple
      headspace polydimethylsiloxane (PDMS) sorptive extraction technique (HSSE),
      thermally desorbed into a gas chromatographic capillary column and detected and
      identified by gas chromatography-time-of-flight mass spectrometry (GC-TOFMS). The
      method was used to compare metabolite profiles of seven species of fungi grown on
      two types of sterile agars - potato dextrose and Sabouraud dextrose. Three
      species from the genus Penicillium (P. italicum, P. camemberti, and P.
      roqueforti) and four outgroups, each from a different phylum (Saprolegnia sp.;
      Sordaria fimicola, wild-type; Coprinus cinereus; and Rhizopus stolonifer) were
      grown on the two types of agars and analyzed. Multivariate analysis (PCA) was
      used to determine whether separate classes of fungi can be distinguished from one
      another based on their metabolite profiles. PCA showed clear class separation
      between the three Penicillium samples and the outgroups. Slight differences were
      observed in metabolite profiles as a function of growth medium. HSSE/GC-TOFMS
      appears to be a relatively simple and accurate technique for classification of
      fungi based on their volatile metabolite profiles. The volatiles sampling
      technique reported here is non-destructive, so it can be applied with traditional
      methods for studying fungal growth and metabolism.

PMID- 18625273
TI  - Reappraisal (but not distraction) is going to make you sweat: physiological
      evidence for self-control effort.
AB  - Previous studies of emotion regulation suggested that reappraisal (construing an
      emotional event in non-emotional terms) has no cognitive or physiological
      consequences, but in all these studies, reappraisal was instructed ahead of an
      emotional situation. The authors' recent work, using behavioral indices, showed
      that inhibitory self-control resources are challenged when reappraisal starts
      late during an emotional situation relative to late instruction of distraction
      (diverting attention through producing neutral thoughts). The present study
      provides converging physiological evidence in showing that instructing to use
      reappraisal but not distraction late in a sadness inducing film involved
      increased skin conductance and decreased finger temperature. Both of these
      results are indicative of increased sympathetic activation that has been
      previously found to accompany inhibitory self-control effort.

PMID- 18625274
TI  - Structural and functional analysis of virus factories purified from Rabbit
      vesivirus-infected Vero cells.
AB  - Rabbit vesivirus infection induces membrane modifications and accumulation of
      vesicular structures in the cytoplasm of infected Vero cells. Crude RaV
      replication complexes (RCs) have been purified and their structural and
      functional properties have been characterized. We show that calnexin, an ER
      resident protein, RaV non-structural proteins 2AB-, 2C-, 3A-, 3B- and 3CD-like as
      well as viral RNAs co-localize within membranous structures which are able to
      replicate the endogenous RNA templates. The purified virus factories protected
      their viral RNA contents from microccocal nuclease degradation and were
      inaccessible to exogenously added synthetic transcripts. In addition, we have
      shown that RCs can be used to investigate uridylylation of native endogenous VPg.
      In contrast to the observation that the virus factories were inaccessible to
      RNAs, RCs were accessible to added recombinant VPg which was subsequently
      nucleotidylylated. Nevertheless no elongation of an RNA chain attached to native
      or recombinant VPg could be demonstrated.

PMID- 18625275
TI  - Stability issues of polymeric micelles.

PMID- 18625276
TI  - Calcitonin gene-related peptide-mediated antihypertensive and anti-platelet
      effects by rutaecarpine in spontaneously hypertensive rats.
AB  - We have previously reported that Chinese traditional medicine rutaecarpine (Rut)
      produced a sustained hypotensive effect in phenol-induced and two-kidney, one
      clip hypertensive rats. The aims of this study are to determine whether Rut could
      exert antihypertensive and anti-platelet effects in spontaneously hypertensive
      rats (SHR) and the underlying mechanisms. In vivo, SHR were given Rut and the
      blood pressure was monitored. Blood was collected for the measurements of
      calcitonin gene-related peptide (CGRP), tissue factor (TF) concentration and
      activity, and platelet aggregation, and the dorsal root ganglia were saved for
      examining CGRP expression. In vitro, the effects of Rut and CGRP on platelet
      aggregation were measured, and the effect of CGRP on platelet-derived TF release
      was also determined. Rut exerted a sustained hypotensive effect in SHR
      concomitantly with the increased synthesis and release of CGRP. The treatment of
      Rut also showed an inhibitory effect on platelet aggregation concomitantly with
      the decreased TF activity and TF antigen level in plasma. Study in vitro showed
      an inhibitory effect of Rut on platelet aggregation in the presence of thoracic
      aorta, which was abolished by capsazepine or CGRP(8-37), an antagonist of
      vanilloid receptor or CGRP receptor. Exogenous CGRP was able to inhibit both
      platelet aggregation and the release of platelet-derived TF, which were abolished
      by CGRP(8-37). The results suggest that Rut exerts both antihypertensive and anti
      platelet effects through stimulating the synthesis and release of CGRP in SHR,
      and CGRP-mediated anti-platelet effect is related to inhibiting the release of
      platelet-derived TF.

PMID- 18625277
TI  - Role of alpha-melanocyte stimulating hormone and melanocortin 4 receptor in brain
      inflammation.
AB  - Inflammatory processes contribute widely to the development of neurodegenerative
      diseases. The expression of many inflammatory mediators was found to be increased
      in central nervous system (CNS) disorders suggesting that these molecules are
      major contributors to neuronal damage. Melanocortins are neuropeptides that have
      been implicated in a wide range of physiological processes. The melanocortin
      alpha-melanocyte stimulating hormone (alpha-MSH) has pleiotropic functions and
      exerts potent anti-inflammatory actions by antagonizing the effects of pro
      inflammatory cytokines and by decreasing important inflammatory mediators. Five
      subtypes of melanocortin receptors (MC1R-MC5R) have been identified. Of these,
      the MC4 receptor is expressed predominantly throughout the CNS. Evidence of
      effectiveness of selective MC4R agonists in modulating inflammatory processes and
      their low toxicity suggest that these molecules may be useful in the treatment of
      CNS disorders with an inflammatory component. This review describes the
      involvement of the MC4R in central anti-inflammatory effects of melanocortins and
      discusses the potential value of MC4R agonists for the treatment of inflammatory
      related disorders.

PMID- 18625278
TI  - Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for
      rheumatoid arthritis in a genetically homogeneous population.
AB  - Rheumatoid arthritis (RA) is a multifactorial disease that is increasing in
      incidence worldwide. It is associated with a complex mode of inheritance, with
      many genes being involved in the development and progression of the disease.
      Genome-wide association studies in different populations have recently revealed a
      significant association between a TRAF1/C5 and a STAT4 polymorphism and the
      development of RA. In the present study we performed a case-control study in the
      population of the island of Crete, Greece, aiming to replicate the former
      findings in a genetically homogeneous cohort of patients. We found that mutated
      allele A or genotypes A/A and G/A of the TRAF1/C5 rs10818488 SNP were more common
      in individuals with RA than in control individuals (odds ratio [OR]=1.7, 95%
      confidence interval [CI]=1.35-2.15, and OR=2.22, 95% CI=1.61-3.05, respectively).
      Similarly, mutated allele T or genotypes T/T and G/T of the STAT4 rs7574865 SNP
      were also associated with susceptibility to RA (OR=1.9, 95% CI=1.46-2.50, and
      OR=2.37, 95% CI 1.73-2.25, respectively). Thus, we conclude that mutant alleles
      or genotypes of both polymorphisms examined are associated with the development
      of RA in our population.

PMID- 18625279
TI  - Government financing for health and specific national budget lines: the case of
      vaccines and immunization.
AB  - A long standing question related to immunization financing and sustainability has
      been whether the existence of a specific line item for vaccines purchasing within
      the national health budget can contribute significantly to increasing national
      government financing of vaccines and routine immunizations. Based on immunization
      financing indicators from 185 countries collected through the joint WHO and
      UNICEF monitoring system, this paper attempts to answer this policy question. The
      study will present findings related to the status of countries that have such
      specific budget lines for purchasing vaccines and the levels of national
      budgetary allocation to the financing of vaccines and immunizations, particularly
      in low-income countries. The analysis shows evidence that the existence ofa
      specific line in the national budget is associated with increased governmental
      budget allocations for vaccines and routine immunization financing.

PMID- 18625281
TI  - The use of mycobacterial adjuvant-based agents for immunotherapy of cancer.
AB  - A heat-killed preparation of Mycobacterium vaccae (SRL172) has been shown, in
      recent studies, to be effective in the treatment of adenocarcinoma of the lung
      and renal cell cancer. It is postulated that the mechanisms of this form of
      immunotherapy is, at least in part, due to immune regulation, reflected in the
      selective enhancement of Th1 and down-regulation of Th2 T cell activity. These
      beneficial effects are attributed to the ability of adjuvants in the bacterial
      cell walls to modify and optimise the response to antigens shared by the bacteria
      and stressed host tissues, resulting in the destruction of cancer cells by
      programmed cell death or apoptosis. The M. vaccae-induced apoptosis appears to be
      most effective against carcinomas, perhaps especially those of glandular tissue,
      in contrast to pyrexia-induced necrosis which is most effective against tumours
      of mesodermal origin. In view of the great range of adjuvants, especially in the
      genus Mycobacterium and related genera, it may prove possible to develop a range
      of immunotherapeutic agents with useful activity against a wide range of cancers.

PMID- 18625280
TI  - A combination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT
      dendritic cells for prolonged mucosal immunity.
AB  - We explore cellular and molecular mechanisms of nasal adjuvant of a combination
      of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligodeoxynucleotides
      (CpG ODN). The double DNA adjuvant given with OVA maintained prolonged OVA
      specific secretory IgA (S-IgA) Ab responses in external secretions for more than
      25 weeks after the final immunization. Further, both Th1- and Th2-type cytokine
      responses were induced by this combined adjuvant regimen. The frequencies of
      plasmacytoid DCs (pDCs) and CD8(+) DCs were significantly increased in
      nasopharyngeal-associated lymphoreticular tissue (NALT) of mice given the
      combined adjuvant. Importantly, when we examined adjuvanticity of pFL plus CpG
      ODN in 2-year-old mice, significant levels of mucosal IgA Ab responses were also
      induced. These results demonstrate that nasal delivery of a combined DNA adjuvant
      offers an attractive possibility for the development of an effective mucosal
      vaccine for the elderly.

PMID- 18625282
TI  - Cadmium regulation of apoptotic and stress response genes in tumoral and
      immortalized epithelial cells of the human breast.
AB  - Cadmium (Cd) is a widely-disseminated metal which can be imported and accumulated
      in living cells thereby drastically interfering with their biological mechanisms.
      Increasing interest has been recently focused on the elucidation of the cellular
      and molecular aspects of Cd-dependent regulation of gene expression and signal
      transduction pathways in different model system. Concerning breast cancer, very
      limited studies have been produced so far on the role played by Cd on estrogen
      receptor-negative human breast cancer cells, that are expected to be insensitive
      to the already-proven metallo-estrogenic effect exerted by Cd on the estrogen
      receptor-positive cell counterparts. Here, we have examined the effects of long
      term (96 h) exposure of estrogen receptor-negative MDA-MB231 malignant
      adenocarcinoma cells to CdCl(2) at 5 microM concentration, corresponding to the
      IC(50) for this time of incubation, by evaluating the expression levels of genes
      coding for stress response factors (e.g. heat shock proteins and
      metallothioneins), and for apoptosis-related factors and enzymes. In parallel, we
      tested the gene expression pattern of immortalized HB2 breast epithelial cells,
      taken as non-tumoral counterpart, after the same exposure to the metal which
      instead did not exert any change in their cell number with respect to controls.
      Our cumulative results indicate that, whilst HB2 cells appear to activate defense
      mechanisms against metal stress principally via metallothionein massive up
      regulation and appearance of the spliced form of XBP-1 message, MDA-MB231 cells
      seem to couple the onset of a protective reaction (e.g. up-regulation of hsp27
      and metallothioneins) to the switching-on of new intracellular pathways directing
      cells to a kind of death which shares several aspects with the apoptotic program,
      such as down-regulation of Bcl-2 and over-expression of Dap kinase and several
      caspases.

PMID- 18625283
TI  - Bactericidal effect of lactoferrin and lactoferrin chimera against halophilic
      Vibrio parahaemolyticus.
AB  - Infections caused by Vibrio parahaemolyticus, an halophilic member of the genus
      Vibrio, have increased globally in the last 5 years. Diarrhea caused by V.
      parahaemolyticus results from eating raw or undercooked seafood. The aim of this
      work was to investigate whether lactoferrin and some lactoferrin-peptides have
      bactericidal activity against Vibrio parahaemolyticus ATCC 17802, the pandemic
      strain O3:K6, and the multidrug resistant isolate 727, as well as against Vibrio
      cholerae strains O1 and non-O1. Whereas both peptides lactoferricin (17-30) and
      lactoferrampin (265-284) did not have bactericidal activity, 40 microM of
      lactoferrin chimera (a fusion of the two peptides) inhibited the growth of all
      Vibrio tested to the same extent as the antibiotic gentamicin. The cidal effect
      of LFchimera showed a clear concentration response in contrast to bovine
      lactoferrin which showed higher inhibition at 10 microM than at 40 microM. FITC
      labeled LFchimera bound to the bacterial membranes. Moreover LFchimera
      permeabilized bacterial cells and membranes were seriously damaged. Finally, in
      experiments with the multidrug resistant isolate 727, sub-lethal doses of
      LFchimera strongly reduced the concentrations of ampicillin, gentamicin or
      kanamicin needed to reach more than 95% growth inhibition, suggesting synergistic
      effects. These data indicate that LFchimera is a potential candidate to combat
      the multidrug resistant pathogenic Vibrio species.

PMID- 18625284
TI  - Seed defensins of barnyard grass Echinochloa crusgalli (L.) Beauv.
AB  - From the annual weed barnyard grass Echinochloa crusgalli (L.) Beauv., two novel
      defensins Ec-AMP-D1 and Ec-AMP-D2 that differ by a single amino acid substitution
      were isolated by a combination of different chromatographic procedures. Both
      defensins were active against several phytopathogenic fungi and the oomycete
      Phytophthora infestans at micromolar concentrations. The Ec-AMP-D1 showed higher
      activity against the oomycete than Ec-AMP-D2. The comparison of the amino acid
      sequences of the antifungal E. crusgalli defensins with those of earlier
      characterized T. kiharae defensins [T.I. Odintsova, Ts.A. Egorov, A.Kh.
      Musolyamov, M.S. Odintsova, V.A. Pukhalsky, E.V. Grishin, Seed defensins from T.
      kiharae and related species: genome localization of defensin-encoding genes,
      Biochimie, 89 (2007) 605-612.] that were devoid of substantial antifungal
      activity point to the C-terminal region of the molecule as the main determinant
      of the antifungal activity of E. crusgalli defensins.

PMID- 18625285
TI  - Corticosterone release in oxytocin gene deletion mice following exposure to
      psychogenic versus non-psychogenic stress.
AB  - Both anxiety-related behavior [J.A. Amico, R.C. Mantella, R.R. Vollmer, X. Li,
      Anxiety and stress responses in female oxytocin deficient mice, J.
      Neuroendocrinol. 16 (2004) 1-6; R.C. Mantella, R.R. Vollmer, X. Li, J.A. Amico,
      Female oxytocin-deficient mice display enhanced anxiety-related behavior,
      Endocrinology 144 (2003) 2291-2296] and the release of corticosterone following a
      psychogenic stress such as exposure to platform shaker was greater in female
      [J.A. Amico, R.C. Mantella, R.R. Vollmer, X. Li, Anxiety and stress responses in
      female oxytocin deficient mice, J. Neuroendocrinol. 16 (2004) 1-6; R.C. Mantella,
      R.R. Vollmer, L. Rinaman, X. Li, J.A. Amico, Enhanced corticosterone
      concentrations and attenuated Fos expression in the medial amygdala of female
      oxytocin knockout mice exposed to psychogenic stress, Am. J. Physiol. Regul.
      Integr. Comp. Physiol. 287 (2004) R1494-R1504], but not male [R.C. Mantella, R.R.
      Vollmer, J.A. Amico, Corticosterone release is heightened in food or water
      deprived oxytocin deficient male mice, Brain Res. 1058 (2005) 56-61], oxytocin
      gene deletion (OTKO) mice compared to wild type (WT) cohorts. In the present
      study we exposed OTKO and WT female mice to another psychogenic stress, inserting
      a rectal probe to record body temperature followed by brief confinement in a
      metabolic cage, and measured plasma corticosterone following the stress. OTKO
      mice released more corticosterone than WT mice (P<0.03) following exposure to
      this stress. In contrast, if OTKO and WT female and male mice were administered
      insulin-induced hypoglycemia, an acute physical stress, corticosterone release
      was not different between genotypes. The absence of central OT signaling pathways
      in female mice heightens the neuroendocrine (e.g., corticosterone) response to
      psychogenic stress, but not to the physical stress of insulin-induced
      hypoglycemia.

PMID- 18625286
TI  - Event-related potential correlates of perceptual and functional categories:
      comparison between stimuli matching by identity and equivalence.
AB  - Event-related potentials (ERPs) correlates of two test criteria of an abstract
      category task were dissociated. In a stimulus equivalence task, 10 subjects
      observed pairs of figures presented serially in three conditions: reflexivity
      (generalized identity), equivalence (arbitrary derived relations from a previous
      training), and unrelated pairs. They were instructed to decide whether the second
      item in a pair matched or mismatched the first one. Participants' performance in
      reflexivity matching tests was faster and more accurate than in equivalence
      matching or mismatching responses. In the three conditions, an occipital P2, a
      frontal N2 and a parietal P3 ERP component were elicited. The earlier components
      P2 and N2 exhibited reflexivity matching effects, while the later component (P3)
      exhibited the only equivalence matching effect. In addition, the subtracted ERP
      components from unrelated minus identity and unrelated minus equivalence trials
      were computed within two time windows: 150-250ms (dN300) and 350-450ms (dN400).
      While both dN300 waves were not significantly different, the comparison of both
      dN400 waves showed statistical differences. Correlates of partially perceptual
      (but contextually abstract) concepts are elicited earlier than those of pure
      abstract concepts. These ERPs correlates of stimulus equivalence relation tests
      of semantic categories are in concordance with the behavioral data.

PMID- 18625287
TI  - Effect of navigation direction on the dual-task of counting backward during blind
      navigation.
AB  - Blind navigation towards a remembered target is associated with large direction
      errors when executed with a side stepping walking pattern. To investigate whether
      sideways navigation requires higher attention resource than forward navigation, a
      dual-task paradigm of backward counting during blind navigation was used. The
      objectives were to determine the effect of this dual-task on navigation errors,
      gait velocity and the rate of backward counting and to establish whether this
      effect is larger during sideways than forward navigation. A group of 17 subjects
      participated. The primary task was to navigate without vision towards previously
      seen targets located on the floor 8m away in four directions (ahead, behind, to
      the right or left) and to stop at the place the target was presumed to be.
      Forward, backward and side stepping gait patterns were used to reach
      corresponding targets. The secondary task was to count backwards in steps of
      three. The dual-task was to perform blind navigation while counting backwards.
      The rate of backward counting was significantly decreased in the dual-task
      relative to a controlled sitting condition (p<0.05), but this reduction was
      similar among navigation directions. Navigation errors were not changed between
      navigation only and dual-task. Gait velocity was significantly slower in the dual
      task than in navigation only (p<0.05). This suggests that counting backward while
      navigating without vision towards a remembered target exceeded the subjects'
      attention capacity. However, sideways navigation did not seem to require more
      attention than forward navigation, even though navigation was much less precise
      in sideways than forward navigation.

PMID- 18625288
TI  - Environmental enrichment, exercise and corticosterone affect endothelial cell
      proliferation in adult rat hippocampus and prefrontal cortex.
AB  - Stress and environmental enrichment have opposing effects on cerebral cellular
      plasticity. Stress-induced disturbances in neuronal and glial plasticity have
      been implicated in the pathophysiology of affective disorders. Patients with
      depression often show volume reductions in specific brain regions. The mechanisms
      behind these changes are not well understood, but animal studies have indicated
      that increased levels of glucocorticoids and stress have negative impact on the
      neuronal and glial cell populations. On the contrary, enriched environment and
      physical activity have positive effects. In this study we have examined the
      effect of corticosterone (CORT), environmental enrichment (EE) and running on
      angiogenesis in hippocampus and prefrontal cortex (PFC). We demonstrate a
      dramatic inhibition in endothelial cell proliferation in these brain regions in
      CORT-treated rats. Environmental enrichment had the opposite effect and
      stimulated endothelial cell proliferation both in the hippocampus and in the PFC.
      Running had a stimulatory effect in hippocampus, but not in the PFC. We suggest
      that the angiostatic effect of CORT demonstrated in this study might be
      paralleled in human subjects exposed to high levels of stress hormones for
      prolonged periods of time. Raised cortisol levels in depressed or old patients
      could, by reducing endothelial cell formation/turnover, lead to rarefaction and
      aging of the vascular bed, and as a result, neuronal function could be impaired.
      It is tempting to speculate that a physically and intellectually active life may
      protect against stress-induced vascular changes. Therapeutic agents also
      targeting the cerebral vasculature could consequently constitute a new tool in
      the combat of stress-related disorders.

PMID- 18625289
TI  - Intestinal epithelial CD98: an oligomeric and multifunctional protein.
AB  - The intestinal epithelial cell-surface molecule, CD98 is a type II membrane
      glycoprotein. Molecular orientation studies have demonstrated that the C-terminal
      tail of human CD98 (hCD98), which contains a PDZ-binding domain, is
      extracellular. In intestinal epithelial cells, CD98 is covalently linked to an
      amino-acid transporter with which it forms a heterodimer. This heterodimer
      associates with beta(1)-integrin and intercellular adhesion molecular 1 (ICAM-1)
      to form a macromolecular complex in the basolateral membranes of polarized
      intestinal epithelial cells. This review focuses on the multifunctional roles of
      CD98, including involvement in extracellular signaling, adhesion/polarity, and
      amino-acid transporter expression in intestinal epithelia. A role for CD98 in
      intestinal inflammation, such as Intestinal Bowel Disease (IBD), is also
      proposed.

PMID- 18625290
TI  - Neuroprotective effects of dihydroprogesterone and progesterone in an
      experimental model of nerve crush injury.
AB  - A satisfactory management to ensure a full restoration of peripheral nerve after
      trauma is not yet available. Using an experimental protocol, in which crush
      injury was applied 1 cm above the bifurcation of the rat sciatic nerve for 20 s,
      we here demonstrate that the levels of neuroactive steroids, such as pregnenolone
      and progesterone (P) metabolites (i.e. dihydroprogesterone, DHP, and
      tetrahydroprogesterone, THP) present in injured sciatic nerve were significantly
      decreased. On this basis, we have focused our attention on DHP and its direct
      precursor, P, analyzing whether these two neuroactive steroids may have
      neuroprotective effects on biochemical, functional and morphological alterations
      occurring during crush-induced degeneration-regeneration. We demonstrate that DHP
      and/or P counteract biochemical alterations (i.e. myelin proteins and Na(+),K(+)
      ATPase pump) and stimulate reelin gene expression. These two neuroactive steroids
      also counteract nociception impairment, and DHP treatment significantly decreases
      the up-regulation of myelinated fibers' density occurring in crushed animals.
      Altogether, these observations suggest that DHP and P (i.e. two neuroactive
      steroids interacting with progesterone receptor) may be considered protective
      agents in case of nerve crush injury.

PMID- 18625291
TI  - Localization and possible function of P2Y(4) receptors in the rodent retina.
AB  - Extracellular ATP acts as a neurotransmitter in the retina, via the activation of
      ionotropic P2X receptors and metabotropic P2Y receptors. The expression of
      various P2X and P2Y receptor subtypes has been demonstrated in the retina, but
      the localization of P2Y receptors and their role in retinal signaling remains ill
      defined. In this study, we were interested in determining the localization of the
      P2Y(4) receptor subtype in the rat retina, and using the electroretinogram (ERG)
      to assess whether activation of these receptors modulated visual transmission.
      Using light and electron microscopy, we demonstrated that P2Y(4) receptors were
      expressed pre-synaptically in rod bipolar cells and in processes postsynaptic to
      cone bipolar cells. Furthermore, we show that the expression of P2Y(4) receptors
      on rod bipolar cell axon terminals is reduced following dark adaptation,
      suggesting receptor expression may be dependent on retinal activity. Finally,
      using the electroretinogram, we show that intravitreal injection of uridine
      triphosphate, a P2Y receptor agonist, decreases the amplitude of the rod PII,
      supporting a role for P2Y receptors in altering inner retinal function. Taken
      together, these results suggest a role for P2Y(4) receptors in the modulation of
      inner retinal signaling.

PMID- 18625292
TI  - Altruism among relatives and non-relatives.
AB  - Hamilton's [Hamilton, W.D., 1964. The genetical evolution of social behavior, I,
      II. J. Theor. Biol. 7, 1-52] kin-selection theory predicts that altruism will be
      greater with greater genetic overlap (degree of kinship) between giver and
      receiver. Kin may be identified in terms of social distance-the closer you feel
      to someone else, (a) the greater your genetic overlap with them should be, and
      (b) the more altruistic you should be toward them. The present experiment
      determined the amount of their own (hypothetical) monetary reward undergraduates
      were willing to forgo in order to give $75 to other people at various social
      distances. We found that (a) genetic relationship and (b) altruism varied
      inversely with social distance; the closer you feel to someone else, the closer
      their relation to you is likely to be, and the more altruistic you are likely to
      be toward them. However, even at the same social distance, participants were
      willing to forgo significantly more money for the benefit of relatives than for
      the benefit of non-relatives. These results are consistent with kin-selection
      theory and imply that altruism is determined by factors in addition to social
      distance.

PMID- 18625293
TI  - Cytotoxicity of oxidised lipids in cultured colonal human intestinal cancer cells
      (caco-2 cells).
AB  - In this study, we investigated the extent of the cytotoxicity effect of oxidised
      lipids and whether tea catechins namely (-)epigallocatechin-3 gallate (EGCG)
      decreased lipid peroxidation in caco-2 cells. Cells treated with 0-100 microg/ml
      fish oil or methyl linoleate (ML) oxidised by UV irradiation for 24 h, 48 h and
      72 h, indicated a substantial decrease in cell viability especially in samples
      treated with 100 microg/ml oxidised lipid. Addition of malondialdehyde (MDA) and
      hydroxynonenal (50 microM) also reduced cell viability. Using EGCG (50 microM)
      increased the viability of cells treated with 24 h oxidised mackerel oil (72%
      live and 28% dead) compared with 48 h oxidised mackerel oil (89% live and 11%
      dead) and 72 h oxidised mackerel oil (71% live and 29% dead) as monitored by the
      MTT assay. Apoptosis of caco-2 cells by oxidised fish oil and ML and protection
      by EGCG was confirmed using fluorescence microscopy and caspase-3 presence by
      Western blotting.

PMID- 18625294
TI  - Effects of photoactivated 5-aminolevulinic acid hexyl ester on MDR1 over
      expressing human uterine sarcoma cells.
AB  - The role of multi-drug resistance (MDR1) and its product, P-glycoprotein (P-gp)
      on 5-aminolevulinic acid hexyl ester (Hexyl-ALA) mediated phototoxicity was
      determined with human uterine sarcoma cells, MES-SA control and MDR1 expressing
      MES-SA-Dx5. MDR1 expression reduced intracellular levels of the Hexyl-ALA
      metabolite, protoporphyrin IX (PpIX) to a limited degree and could be reversed
      with a P-gp inhibitor, verapamil. P-gp expression also reduced Hexyl-ALA
      photosensitivity. More importantly, photoactivated Hexyl-ALA reduced at the mRNA
      and protein levels without altering housekeeping GAPDH mRNA. These findings
      suggest that Hexyl-ALA could be used to selectively reduce P-gp expression in
      overcoming resistance to chemotherapy agents such as doxorubicin and paclitaxel.

PMID- 18625295
TI  - The effect of complexation of Cu(II) with P6A peptide and its analogs on their
      thrombolytic activities.
AB  - The complexation of Cu(II) with previously synthesized thrombolytic peptides, Pro
      Ala-Lys (6), Arg-Pro-Ala-Lys (7), Ala-Arg-Pro-Ala-Lys (8), Gly-Arg-Pro-Ala-Lys
      (9) and Gln-Arg-Pro-Ala-Lys (10), resulted in the formation of complexes, Cu(II)
      (Pro-Ala-Lys) (6-Cu), Cu(II)-(Arg-Pro-Ala-Lys) (7-Cu), Cu(II)-(Ala-Arg-Pro-Ala
      Lys) (8-Cu), Cu(II)-(Gly-Arg-Pro-Ala-Lys) (9-Cu) and Cu(II)-(Gln-Arg-Pro-Ala-Lys)
      (10-Cu), which was confirmed by UV-Vis, circular dichroism and ESI-MS analyses.
      Complexes (6-10)-Cu in normal saline (NS) were found to be able to assemble into
      aggregates, and the size of the aggregates were measured for the next eight
      consecutive days. It was found that on the 8th day, the diameters of (6-10)-Cu
      aggregates ranged from 179.21+/-38.33 nm to 293.46+/-51.07 nm. The Zeta
      potentials of (6-10)-Cu aggregates in NS were also examined and it was found that
      aggregates of (6, 8, 10)-Cu were negatively charged, and 7-Cu and 9-Cu were
      positively charged. The powders of (6-10)-Cu were analyzed by transmission
      electron microscopy and were found to have mean particle sizes of 8-15 nm. The in
      vitro euglobulin lysis, vasodilation and thrombolytic assays indicated that
      complexation with Cu(II) resulted in a significant increase in the activities of
      6-10. The in vivo thrombolytic assays revealed that complexation with Cu(II)
      resulted in a significant enhancement in the in vivo thrombolytic activities for
      6, 7, 8 and 10 at 10 micromol/kg, and 9 at 1 micromol/kg and 0.1 micromol/kg,
      respectively. These findings suggested that the self-assembly of the Cu(II)
      peptide complexes into nano-scale aggregates was beneficial in improving the
      thrombolytic activity of the peptides.

PMID- 18625296
TI  - The creation of geometric three-dimensional models of the inner ear based on
      micro computer tomography data.
AB  - The modeling of the mechanical process of hearing requires an accurate
      geometrical model of the inner ear (cochlea). The purpose of this study was the
      creation of a 3-D model of the fluid chambers of Guinea pig cochlea, which could
      serve as a basis for further mechanical modeling. Micro computer tomography used
      in this study is a noninvasive method to visualize bony structures. The
      visualization of the membranous labyrinth was achieved by additional staining of
      the specimen with OsO(4). The resulting stack of images has been transformed into
      a cylindrical coordinate system. To suppress noise on tomography images, a
      nonlinear smoothing method, anisotropic diffusion, were applied. A new approach
      has been proposed to estimate algorithm parameters automatically. Then, a
      segmentation using active contours (snakes) was performed. In this study, a new
      energy linking the contours on adjacent slices has been added to the standard
      approach. This compensates the inconsistencies between adjacent contours. The
      images segmented in this way were used as a basis for a 3-D reconstruction of the
      hearing organ.

PMID- 18625297
TI  - The transcriptional response to distinct growth factors is impaired in Werner
      syndrome cells.
AB  - The Werner syndrome protein (WRN) is mutated in Werner syndrome (WS) and plays a
      role in telomere maintenance, DNA repair and transcription. WS represents a
      premature aging syndrome with severe growth retardation. Here we show that WRN is
      critically required to mediate the stimulatory effect of vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (FGF-b) and epidermal growth
      factor (EGF) on the activity of RNA polymerase I (Pol I). Recombinant WRN
      specifically reconstitutes RNA polymerase I transcription in extracts from Werner
      syndrome fibroblasts in vitro. In addition, we identified a critical role for WRN
      during promoter clearance of Pol I transcription, but not in elongation. Notably,
      WRN was isolated in a complex with Pol I and was crosslinked to the unmethylated,
      active proportion of rDNA genes in quiescent cells suggesting a so far unknown
      role for WRN in epigenetic regulation. This together with alterations in Pol I
      transcription provide a novel mechanism possibly underlying at least in part the
      severe growth retardation and premature aging in Werner syndrome patients.

PMID- 18625298
TI  - Fluoxetine directly counteracts the adverse effects of chronic stress on T cell
      immunity by compensatory and specific mechanisms.
AB  - Chronic stress and depression are widely known to down-regulate the immune
      system, and several antidepressants can reverse this impairment, with or without
      effects in normal subjects. Although the central nervous system is undoubtedly
      involved in these events, some psychotropic drugs can also exert direct effects
      on lymphoid cells. We have recently shown that the antidepressant fluoxetine
      enhances T cell proliferation and T(H)1 cytokine production in vivo, without
      changes on CD4/CD8 subsets. In vitro, a direct action of fluoxetine upon T
      lymphocyte reactivity by complex mechanisms was also described. In another work,
      we also found that chronic stress reduces T cell mediated immunity, namely a
      decrease of T cell response to mitogens, T(H)1 cytokine production and CD4+-but
      not CD8+--T lymphocytes. Here we investigated the effects of fluoxetine on
      chronic stress-driven immune system depression. We found that fluoxetine restored
      T cell proliferation and interleukin-2, interferon-gamma and tumor necrosis
      factor-alpha production by compensatory mechanisms. In addition, CD4/CD8 ratio
      was also normalized by antidepressant administration, but this seems to be a non
      compensatory effect associated specifically to stress. No changes were observed
      in other lymphoid cells, i.e. natural killer cells and B lymphocytes. Finally, we
      observed that fluoxetine is able to reverse T cell reactivity impairment in vitro
      by a direct action at clinically relevant doses. These results highlight the
      relevance of pharmacological treatment of stress and depression, and may help to
      begin elucidating the complex events triggered--directly and/or indirectly--by
      antidepressants in non-neuronal cell types.

PMID- 18625299
TI  - Effects of autoimmunity on recovery of function in adult rats following spinal
      cord injury.
AB  - The central nervous system (CNS) is considered to be an immune-privileged site.
      For a long time, autoimmunity-induced inflammation has been viewed as an
      important mediator of secondary damage in the CNS following injury. However,
      other studies also suggest that autoimmunity is protective and beneficial. To
      investigate whether protective autoimmunity is present following spinal cord
      injury (SCI), we employed neonatally thymectomized (Tx) rats which contain few T
      lymphocytes in their peripheral blood, and passively immunized them with T
      lymphocytes activated by myelin basic protein (MBP) or spinal cord homogenate
      (SCH). Here we report that, among Tx, sham-Tx (sTx) and normal rats that received
      a contusive SCI, no significant histological and behavioral differences were
      found, suggesting that the endogenous T lymphocytes had no significant influence
      on the pathogenesis of secondary SCI. In rats passively immunized with MBP- or
      SCH-activated T cells (MBP-T or SCH-T, respectively), similar numbers of CD4(+) T
      cells were found to infiltrate into the injured spinal cords. However, only the
      MBP-T immunization showed neuroprotection, evidenced by the reduction of post
      traumatic neuronal losses and improvement of functional recovery. These results
      collectively suggest that not all T lymphocytes against CNS antigens are
      neuroprotective and that a subpopulation of them, such as those of MBP-T cells,
      could be beneficial for SCI repair.

PMID- 18625300
TI  - Hypochlorous acid oxidizes methionine and tryptophan residues in myoglobin.
AB  - After acute myocardial infarction (AMI), infiltrating proinflammatory cells
      generate two-electron oxidants such as hypochlorous acid (HOCl). Myoglobin (Mb)
      is present at approximately 0.3 mM in cardiomyocytes and, therefore, represents a
      significant target for oxidation. Exposure of horse Mb (50 microM) to reagent
      HOCl (0-500 microM) or activated human neutrophils (4-40x10(6) cells/ml) yielded
      oxidized Mb (Mb(ox)) as judged by amino acid analysis and peptide mass mapping.
      HOCl/Mb ratios of 1-5 mol/mol gave Mb(ox) with up to four additional oxygen
      atoms. Hydrolysis of Mb(ox) followed by amino acid analysis indicated that
      methionine (Met) and tryptophan (Trp) residues were modified by HOCl. Peptide
      mass mapping revealed that Met55 was oxidized at a lower HOCl/Mb ratio than
      Met131 and this preceded Trp7/14 modification (susceptibility
      Met55>Met131>Trp7>Trp14). Incubation of Mb with activated neutrophils and
      physiological chloride anion yielded Mb(ox) with a composition similar to that
      determined with HOCl/Mb ratios <2 mol/mol, with oxidation of Met, but not Trp,
      detected. These data indicate that Mb undergoes site-specific oxidation depending
      on the HOCl/protein ratio. As Mb is released from necrotic cardiomyocytes into
      the vasculature after AMI, HOCl-modified Mb may be a useful surrogate marker to
      gauge the extent of myocardial inflammation.

PMID- 18625302
TI  - Cdk5 phosphorylates PLD2 to mediate EGF-dependent insulin secretion.
AB  - Insulin secretion from pancreatic beta-cells is an important process that affects
      the regulation of glucose level in the blood. In our previous study, we suggested
      that epidermal growth factor (EGF) stimulates insulin secretion by activating
      phospholipase D2 (PLD2) [H.Y. Lee, K. Yea, J. Kim, B.D. Lee, Y.C. Chae, H.S. Kim,
      D.W. Lee, S.H. Kim, J.H. Cho, C.J. Jin, D.S. Koh, K.S. Park, P.G. Suh, S.H. Ryu,
      2007. Epidermal Growth Factor Increases Insulin Secretion and Lowers Blood
      Glucose in Diabetic Mice. J. Cell. Mol. Med. 5:5]. However, the specific
      mechanism by which PLD2 activation leads to insulin secretion was not determined.
      In this study, we suggest that the phosphorylation and activation of PLD2 by
      cyclin-dependent kinase 5 (Cdk5) is critical for EGF-dependent insulin secretion.
      We found that a Cdk5 inhibitor, roscovitine, and dominant-negative Cdk5 inhibited
      EGF-dependent PLD2 activation and insulin secretion. EGF stimulation activated
      Cdk5 activity in rat insulinoma RINm5F cells, and PLD2 phosphorylation by Cdk5
      was observed in vitro and in cells. The kinetics of PLD2 phosphorylation
      correlates with the interaction between PLD2 and Cdk5 and its effect on EGF
      signaling. We determined that the phosphorylation site of PLD2 was located at
      Ser(134). PLD2-S134A did not show EGF-dependent phosphorylation and activation by
      Cdk5. Furthermore, this mutant was unable to mediate EGF-dependent insulin
      secretion in pancreatic beta cell lines, suggesting that the phosphorylation of
      PLD2 at Ser(134) by Cdk5 is critical for this process. The study results suggest
      that PLD2 is a new substrate of Cdk5 and that the phosphorylation of PLD2 by Cdk5
      is involved in EGF-dependent insulin secretion.

PMID- 18625301
TI  - Ethyl pyruvate has an anti-inflammatory effect by inhibiting ROS-dependent STAT
      signaling in activated microglia.
AB  - Ethyl pyruvate (EP) has been demonstrated to have an anti-inflammatory function.
      However, the molecular mechanisms underlying the anti-inflammatory action of EP
      are largely unknown. We here show that EP exerts its anti-inflammatory effect by
      inhibiting ROS-dependent STAT signaling through its antioxidant activity, like
      vitamin C or N-acetyl-L-cysteine. The inhibition of STAT1 and STAT3 by EP
      prevented their translocation to the nucleus and consequently inhibited
      expression of iNOS and COX-2 by inhibiting STAT1- and STAT3-mediated
      transcriptional activity, followed by changes in chromatin conformation via
      deacetylation of histones H3 and H4 in both gene promoters. EP also suppressed
      transcripts of other STAT-responsive inflammatory genes such as IL-1beta, IL-6,
      TNF-alpha, and MCP-1. We further found that the mechanism of inhibition of STAT1
      and STAT3 by EP is due to inhibition of JAK2 through Rac1 inactivation and SOCS1
      induction. These findings offer new therapeutic possibilities for EP based on a
      better understanding of the mechanism underlying the action of EP.

PMID- 18625303
TI  - Identification of a novel di-leucine motif mediating K(+)/Cl(-) cotransporter
      KCC2 constitutive endocytosis.
AB  - The neuron-specific potassium-chloride cotransporter 2 (KCC2) plays a crucial
      role, by controlling chloride extrusion, in the development and maintenance of
      inhibitory neurotransmission. Although it is now well established that activity
      dependent mechanisms can down regulate KCC2 gene expression, the role of post
      translational mechanisms in controlling KCC2 expression, specifically at the cell
      surface, are poorly understood. We therefore set out to identify the mechanisms
      and motifs regulating KCC2 endocytosis, one important pathway that may control
      KCC2 membrane expression. Using a fluorescence-based assay, we show KCC2 when
      expressed in HEK293 cells is constitutively internalized via a dynamin- and
      clathrin-dependent pathway. Consistent with this, we demonstrate KCC2 from adult
      mouse brain associates in vivo with the clathrin-binding adaptor protein-2 (AP-2)
      complex. Using an endocytosis reporter system, we identify the presence of an
      autonomous endocytosis motif in the carboxyl cytoplasmic terminus of KCC2. By
      site-directed mutagenesis we define this novel KCC2 endocytic motif as a non
      canonical di-leucine motif, (657)LLXXEE(662). Finally by mutating this motif in
      the context of full-length KCC2 we demonstrate that this novel KCC2 endocytic
      motif is essential for the constitutive internalization of KCC2 and for binding
      to the AP-2 complex. Subsequent sequence analysis reveals this motif is highly
      conserved between the closely related K(+)/Cl(-) family members that mediate
      chloride efflux, but absent from the more distant related cotransporters
      controlling chloride influx. In conclusion, our results indicate constitutive
      internalization of KCC2 is clathrin-mediated and dependent on the binding of AP-2
      to this novel endocytic motif. Furthermore, that this process appears to be an
      evolutionarily conserved mechanism amongst functionally homologous
      cotransporters.

PMID- 18625304
TI  - Virus-like vesicles and extracellular DNA produced by hyperthermophilic archaea
      of the order Thermococcales.
AB  - Cultures of hyperthermophilic archaea (order Thermococcales) have been analyzed
      by electron microscopy and epifluorescence staining for the presence of virus
      like particles. We found that most strains of Thermococcus and Pyrococcus produce
      various types of spherical membrane vesicles and unusual filamentous structures.
      Cellular DNA can be strongly associated with vesicles and appears as fluorescent
      dots by epifluorescence microscopy, suggesting that some particles assumed to be
      viruses in ecological studies might instead be vesicles associated with
      extracellular DNA. DNA in vesicle preparations is remarkably resistant to DNase
      treatment and thermodenaturation, indicating that association with vesicles could
      be an important factor determining DNA stability in natural environments.

PMID- 18625305
TI  - An Escherichia coli asr mutant has decreased fitness during colonization in a
      mouse model.
AB  - The Escherichia coli asr gene, like its homologues in other enterobacteria, is
      strongly induced by low external pH. The E. coli asr mutant shows weakened
      ability to adapt to acidic pH. This suggests that the asr gene product is
      important for enterobacterial species, both commensal and pathogenic, in
      overcoming acid stress in the stomach and subsequently colonizing the intestine.
      We examined the relative fitness of an E. coli asr mutant compared to a wild
      type, by feeding both strains simultaneously to mice and letting them colonize
      the intestine. Analysis of the bacteria after passage through the intestine
      showed up to five orders of magnitude less asr mutant than wild type.
      Transcomplementation of the asr gene on a plasmid partially restored the number
      of mutants. Similar competition in liquid media demonstrated that the asr mutant
      has reduced viability during long-term incubation in rich media, but is as fit as
      the wild type when bacteria are challenged in minimal medium. Competition carried
      out under different pH conditions proved that pH of the media was not the main
      determinant leading to the decreased fitness of the asr mutant. This suggests
      that the asr gene product is important for adaptation to stress conditions other
      than acidity, including long periods of starvation.

PMID- 18625307
TI  - Notch signaling and diseases: an evolutionary journey from a simple beginning to
      complex outcomes.
AB  - Notch signaling pathway regulates a wide variety of cellular processes during
      development and it also plays a crucial role in human diseases. This important
      link is firmly established in cancer, since a rare T-ALL-associated genetic
      lesion has been initially reported to result in deletion of Notch1 ectodomain and
      constitutive activation of its intracellular region. Interestingly, the cellular
      response to Notch signaling can be extremely variable depending on the cell type
      and activation context. Notch signaling triggers signals implicated in promoting
      carcinogenesis and autoimmune diseases, whereas it can also sustain responses
      that are critical to suppress carcinogenesis and to negatively regulate immune
      response. However, Notch signaling induces all these effects via an apparently
      simple signal transduction pathway, diversified into a complex network along
      evolution from Drosophila to mammals. Indeed, an explanation of this paradox
      comes from a number of evidences accumulated during the last few years, which
      dissected the intrinsic canonical and non-canonical components of the Notch
      pathway as well as several modulatory extrinsic signaling events. The
      identification of these signals has shed light onto the mechanisms whereby Notch
      and other pathways collaborate to induce a particular cellular phenotype. In this
      article, we review the role of Notch signaling in cells as diverse as T
      lymphocytes and epithelial cells of the epidermis, with the main focus on
      understanding the mechanisms of Notch versatility.

PMID- 18625306
TI  - Changes in protein structure and distribution observed at pre-clinical stages of
      scrapie pathogenesis.
AB  - Scrapie is a neurodegenerative disorder that involves the misfolding, aggregation
      and accumulation of the prion protein (PrP). The normal cellular PrP (PrP(C)) is
      rich in alpha-helical secondary structure, whereas the disease-associated
      pathogenic form of the protein (PrP(Sc)) has an anomalously high beta-sheet
      content. In this study, protein structural changes were examined in situ in the
      dorsal root ganglia from perorally 263K scrapie-infected and mock-infected
      hamsters using synchrotron Fourier Transform InfraRed Microspectroscopy (FTIRM)
      at four time points over the course of the disease (pre-clinical, 100 and 130
      days post-infection (dpi); first clinical signs ( approximately 145 dpi); and
      terminal ( approximately 170 dpi)). Results showed clear changes in the total
      protein content, structure, and distribution as the disease progressed. At pre
      clinical time points, the scrapie-infected animals exhibited a significant
      increase in protein expression, but the beta-sheet protein content was
      significantly lower than controls. Based on these findings, we suggest that the
      pre-clinical stages of scrapie are characterized by an overexpression of proteins
      low in beta-sheet content. As the disease progressed, the beta-sheet content
      increased significantly. Immunostaining with a PrP-specific antibody, 3F4,
      confirmed that this increase was partly - but not solely - due to the formation
      of PrP(Sc) in the tissue and indicated that other proteins high in beta-sheet
      were produced, either by overexpression or misfolding. Elevated beta-sheet was
      observed near the cell membrane at pre-clinical time points and also in the
      cytoplasm of infected neurons at later stages of infection. At the terminal stage
      of the disease, the protein expression declined significantly, likely due to
      degeneration and death of neurons. These dramatic changes in protein content and
      structure, especially at pre-clinical time points, emphasize the possibility for
      identifying other proteins involved in early pathogenesis, which are important
      for a further understanding of the disease.

PMID- 18625308
TI  - Modulation of buspirone HCl release from hypromellose matrices using chitosan
      succinate: implications for pH-independent release.
AB  - Chitosan succinate (CS) was synthesized through the acylation of chitosan with
      succinic anhydride. The interaction of CS with buspirone HCl (BUSP) was evaluated
      using dialysis experiments and shown to result in complex with a stability
      constant of 2.26 mM and a capacity of 0.0362 micromol BUSP/mg CS. The extent of
      complexation upon dry and wet mixing of CS and BUSP was determined quantitatively
      using differential scanning calorimetry. The extent of the interaction was
      highest in wet mixtures and was found to be dependent on the pH of the
      granulation liquid. CS was incorporated in BUSP-containing hypromellose (HPMC)
      tablets using dry mixing and wet granulation with BUSP. Tablet dissolution was
      tested in 0.1N HCl and phosphate buffer, pH 6.8. According to f(2) and mean
      dissolution time results, the similarity of profiles increased as CS content
      increased with the highest f(2) value observed when CS was wet granulated with
      BUSP. Dissolution was also tested in deionized water and 5% NaCl; where increased
      ionic strength resulted in faster dissolution suggesting an ion exchange
      involvement in drug release. CS was proved effective in modulating BUSP release
      from HPMC matrices for pH-independent release through ionic complex formation.

PMID- 18625309
TI  - Host-pathogen interactions.

PMID- 18625310
TI  - TLR accessory molecules.
AB  - Accessory molecules are required for microbial recognition by Toll-like receptor
      (TLR), subsequent signaling, and regulation of ensuing immune responses.
      Accessory molecules regulate TLRs on the cell surface (MD-2 and RP105), or in the
      endoplasmic reticulum (ER) (Unc93B, PRAT4A, and gp96). Other types of accessory
      molecules modulate TLR responses by acting directly on TLR ligands (CD14, CD36,
      HMGB1, and the antimicrobial peptide LL37). These molecules cooperate with TLR,
      inducing appropriate defense mechanisms. It is important to understand how TLR
      signaling is controlled by these accessory molecules. These accessory molecules
      could be promising targets for therapeutic intervention in infectious disease and
      immune disorders.

PMID- 18625311
TI  - Human embryonic stem cells: emerging technologies and practical applications.
AB  - Human embryonic stem cells possess the unique ability to differentiate into any
      adult cell type. Recent advances in the understanding of stem cell biology make
      new applications possible for stem cell based technology. Of note, it is now
      possible to reprogram terminally differentiated human somatic cells into
      pluripotent cells that are functionally equivalent to embryonic stem cells. These
      induced pluripotent cells may become the substrate for future disease models and
      cell-based therapies. In addition, novel techniques for genetic manipulation have
      increased the ease with which genes can be modified into stem cells. In this
      review, we describe these novel technologies as well as developments in the
      understanding of basic biology of stem cell pluripotency and differentiation.

PMID- 18625313
TI  - The vertebrate segmentation clock: the tip of the iceberg.
AB  - The vertebrate segmentation clock was identified 10 years ago as a molecular
      oscillator associated with the rhythmic production of embryonic somites. Since
      then, three major signaling pathways--Notch, FGF, and Wnt--have been shown to be
      activated periodically during segmentation and proposed to constitute the
      clockwork of the system. However, recent results from zebrafish embryonic studies
      demonstrate that Notch signaling is involved in the coupling of oscillations
      among cells rather than in the pacemaker of the oscillator. Furthermore, genetic
      analyses in mouse indicate that Wnt and FGF play only a permissive role in the
      control of the oscillations. Therefore, the nature of the segmentation clock
      pacemaker still remains elusive.

PMID- 18625312
TI  - The long and the short of Wnt signaling in C. elegans.
AB  - The simplicity of C. elegans makes it an outstanding system to study the role of
      Wnt signaling in development. Many asymmetric cell divisions in C. elegans
      require the Wnt/beta-catenin asymmetry pathway. Recent studies confirm that SYS-1
      is a structurally and functionally divergent beta-catenin, and implicate lipids
      and retrograde trafficking in maintenance of WRM-1/beta-catenin asymmetry. Wnts
      also regulate short-range events such as spindle rotation and gastrulation, and a
      PCP-like pathway regulates asymmetric divisions. Long-range, cell non-autonomous
      Wnt signals regulate vulval induction. Both short-range and long-range Wnt signal
      s are regulated by recycling of MIG-14/Wntless via the retromer complex. These
      studies indicate that C. elegans continues to be useful for identifying new,
      conserved mechanisms underlying Wnt signaling in metazoans.

PMID- 18625314
TI  - Skeletal muscle stem cells.
AB  - In this review we shall discuss recent publications on the heterogeneity of
      muscle stem cells, signaling pathways that affect their behaviour and regulatory
      mechanisms that underlie their myogenic fate, with reference to insights provided
      by work on skeletal muscle formation in the embryo as well as the adult, with the
      mouse as a model of reference.

PMID- 18625315
TI  - Mouse germ cell development during embryogenesis.
AB  - The discrimination and differentiation of germ cells from somatic cells is a
      fundamental issue during development. The early specification of mouse primordial
      germ cells (PGCs) is achieved by the induction of Blimp1, a key regulator of germ
      cells. Nanos3 is one of the genes activated in early PGCs and prevents apoptosis
      during their migration stage. Once PGCs enter the embryonic gonads, they
      differentiate according to the somatic sex of the organism. During this process,
      Nanos2 plays an important role as it promotes male germ cell pathway by
      suppressing the female fate. In this review, the process of germ cell development
      in the mouse is discussed with a particular focus on the functions of the key
      proteins, Blimp1, Nanos, and Dead end1.

PMID- 18625316
TI  - Synthesis and biological effect of halogen substituted phenyl acetic acid
      derivatives of progesterone as potent progesterone receptor antagonists.
AB  - In this paper, we report the relative binding affinities to the progesterone
      receptor (PR) of several progesterone derivatives containing an acetoxyphenyl
      substituent at C-17 and their structure-bioactivity relationship. The inhibitory
      effect to ovulation as well as their function as interrupters of endometrial
      maturation is also described. The biological activity of the novel steroids was
      determined in vivo and in vitro experiments using female cycling mice, which were
      synchronized for estrus with luteinizing hormone-releasing hormone (LHRH) and
      injected with the steroidal compounds. The cytosol used for the determination of
      the PR, was obtained from the uteri of adult estrogen-primed rabbits and the
      androgen (AR), mineralocorticoid (MR) and glucocorticoid (GR) receptors were
      determined in the cytosolic fractions from the prostate of castrated rats and
      from the kidneys and livers of adenalectomized male rats. We evaluated six
      related steroidal compounds 8a-8f differing in the nature of the 17alpha ester
      side chain for the inhibition of [3H] R5020 binding to the PR. The IC50 values
      for the displacement of [3H] R5020 binding to the PR and its relative binding
      affinities (RBAs) were determined. Progesterone and R5020 had similar IC(50)
      values; steroids 8a, 8f and 8c bind to the progesterone receptor with RBAs of
      100%, whereas 8e, 8b and 8d have RBA values <100%. These data indicate that there
      is a relationship between the structure of these steroids and their binding
      activity to the progesterone receptors. Having demonstrated in this study that
      steroids 8a-8f bind to the PR, we also evaluated the receptor's selectivity,
      since some progesterone derivatives bind to AR, MR, GR receptors. We demonstrated
      that the tested steroids did not bind to the AR, MR, GR, since none of the
      steroids inhibited the labeled mibolerone, aldosterone or dexamethasone binding
      to the AR, MR or GR, respectively. These results show that the novel compounds
      have certain selectivity for the PR. After LHRH treatment, the mice of the
      control group showed the presence of ova in the oviduct, whereas the animals
      treated with steroids 8a, 8f, 8e and 8c with RBAs of 92-100%, did not exhibit any
      ovum in the oviducts. As a result of this study, it is evident that the novel
      steroids 8a, 8f, 8e and 8c inhibited the ovulation in these animals at dose of
      0.22 mg/kg. After the treatment with LHRH, the uterus of the control group showed
      the typical progestational activity with an enlarged endometrial thickness with
      secretory activity. However, the endometrium of the mice treated with steroids
      8a, 8f, 8e and 8c (with RBAs of 92-100%) neither did show any enlargement of the
      endometrium, nor a secretory activity could be detected. The diameter of the
      uterus was also significantly reduced compared to those of the control group,
      thus indicating that compounds 8a, 8f, 8e and 8c had antagonistic activity in
      this tissue. The overall data showed that steroids 8a, 8f, 8e and 8c have a high
      and selective binding activity to the PR. Furthermore there is a relationship
      between the structure of these steroids and their binding activity, since the
      presence of fluorine atom in meta position in the acetoxyphenyl substituent at C
      17, improved the binding activity as compared to that for the ortho and para
      positions. These data also demonstrated that 8a-8f have an anti-progestational
      activity in vivo, and therefore they have better characteristics than the
      compounds previously reported.

PMID- 18625317
TI  - Culture condition and embryonic stage dependent silence of glucocorticoid
      receptor expression in hippocampal neurons.
AB  - Glucocorticoid (GC) plays a key role in controlling numerous cellular processes
      during embryogenesis and fetal development. The actions of glucocorticoids are
      mediated by interaction with their receptors. We previously reported that
      hippocampal neurons from embryonic day 18 (E18) rats showed silence of
      glucocorticoid receptor (GR) expression when cultured in serum-free condition. In
      this study, using western blot, immunofluorescence staining and real-time RT-PCR,
      we found that while this silence occurred in hippocampal neurons isolated from
      E16 and E18 rats, it did not happen in those from E20 and neonatal (P0) rats. And
      when cultured under serum-containing condition, none of them showed GR silence
      anymore. Corticosterone could not rescue the expression of GR in E16 and E18
      neurons in serum-free condition, whereas adding of serum could induce the re
      expression of the silenced GR. The absence of GR silence in P0 neurons was not
      due to the perturbation during parturition. Moreover, the unique expression
      profile of GR in protein and mRNA level was well reflected in the changes of GR
      function. These results suggested that under in vitro condition, serum was
      critical for the maintaining of GR expression in hippocampal neurons of early
      embryonic stages but less important in later developmental stages. Thus, our data
      implied that at different developmental stages, the expression of GR in
      hippocampal neurons might have different susceptibilities to environment changes
      and there might be a critical time window for the switching of such
      characteristics during development.

PMID- 18625318
TI  - Expanded CAG repeats in the murine Huntington's disease gene increases neuronal
      differentiation of embryonic and neural stem cells.
AB  - Huntington's disease is an uncommon autosomal dominant neurodegenerative disorder
      caused by expanded polyglutamine repeats. Increased neurogenesis was demonstrated
      recently in Huntington's disease post-mortem samples. In this manuscript,
      neuronally differentiated embryonic stem cells with expanded CAG repeats in the
      murine Huntington's disease homologue and neural progenitors isolated from the
      subventricular zone of an accurate mouse Huntington's disease were examined for
      increased neurogenesis. Embryonic stem cells with expanded CAG repeats in the
      murine Huntington's disease homologue were demonstrated to undergo facilitated
      differentiation first into neural progenitors, then into more mature neurons.
      Neural progenitor cells isolated from the subventricular zone of a Huntington's
      disease knock-in animal displayed increased production of neural progenitors and
      increased neurogenesis. These findings suggested that neuronally differentiating
      embryonic stem cells with expanded CAG repeats is a reasonable system to identify
      factors responsible for increased neurogenesis in Huntington's disease.
      Expression profiling analysis comparing neuronally differentiating embryonic stem
      cells with expanded CAG repeats to neuronally differentiating embryonic stem
      cells without expanded CAG repeats identified transcripts involved in development
      and transcriptional regulation as factors possibly mediating increased
      neurogenesis in response to expanded CAG repeats.

PMID- 18625320
TI  - Static light scattering to characterize membrane proteins in detergent solution.
AB  - Determination of the oligomeric state or the subunit stoichiometry of integral
      membrane proteins in detergent solution is notoriously difficult, because the
      amount of detergent (and lipid) associated with the proteins is usually not
      known. Only two classical methods (sedimentation equilibrium centrifugation and
      static light scattering) can measure directly the absolute molecular mass of a
      protein present in a protein/detergent micelle, without any assumption on the
      amount of detergent bound, or the shape of the proteins. Here the theoretical
      background and practical aspects of static light scattering analysis of membrane
      proteins are reviewed using a number of examples from our lab to highlight
      potential pitfalls. A brief comparison with sedimentation equilibrium
      centrifugation is given and a detailed protocol of how we perform light
      scattering analyses is provided.

PMID- 18625319
TI  - Collybistin is required for both the formation and maintenance of GABAergic
      postsynapses in the hippocampus.
AB  - Collybistin (Cb) is a brain-specific guanine nucleotide exchange factor, which
      interacts with the inhibitory receptor anchoring protein gephyrin. In the
      hippocampus of constitutively Cb-deficient adult mice, gephyrin and gephyrin
      dependent GABA(A) receptors (GABA(A)Rs) are lost from postsynaptic sites. Here,
      we used a Cre-loxP system to inactivate the Cb gene in the forebrain at different
      developmental stages. Deletion of Cb during embryonic development prevented
      gephyrin clustering during synaptogenesis and caused an accumulation of gephyrin
      aggregates in the cell body of CA1 pyramidal neurons. Inactivation of the Cb gene
      during the third postnatal week resulted in a protracted loss of postsynaptic
      gephyrin clusters and the appearance of cytoplasmic gephyrin aggregates. These
      changes in gephyrin distribution were accompanied by a similar reduction in
      synaptically localized GABA(A)R gamma2-subunit immunoreactivity. Our data show
      that Cb is required for both the initial localization and maintenance of gephyrin
      and gephyrin-dependent GABA(A)Rs at inhibitory postsynaptic membrane
      specializations in the hippocampus.

PMID- 18625321
TI  - Expression and purification of the active variant of recombinant murine Golli
      interacting protein (GIP)--characterization of its phosphatase activity and
      interaction with Golli-BG21.
AB  - We have successfully expressed an active variant of recombinant murine GIP
      (rmGIP) with the N-terminal domain deletion (DeltaN-rmGIP) in E. coli
      Rosetta(DE3)-RIPL cells. Whereas DeltaN-rmGIP could be purified under native
      conditions, the purification of full-length rmGIP required denaturing conditions;
      and the yields were 31.4 mg and 7.4 mg per L of culture, respectively. Purity was
      at least 97% as assessed by HPLC. Both proteins exhibited a well-defined
      secondary structure composition as determined by circular dichroism spectroscopy,
      with a slightly higher ratio of helical and strand components in DeltaN-rmGIP.
      The phosphatase activity of both proteins was Mg(2+)-dependent, with a pK(Mg) of
      activation being approximately 2.8 and non-cooperative binding. The Golli-myelin
      basic protein isoform rmBG21 (recombinant murine form) enhanced the phosphatase
      activity of DeltaN-rmGIP below 6 microM, but significantly inhibited it at higher
      concentrations. Using glutaraldehyde cross-linking and gel shift assays, the
      rmBG21-DeltaN-rmGIP interaction was shown to be equimolar and specific, but
      seemingly relatively weak, suggesting that a third interaction partner is
      required in vivo.

PMID- 18625322
TI  - Micro- and nanostructure of the adhesive material secreted by the tube feet of
      the sea star Asterias rubens.
AB  - To attach to underwater surfaces, sea stars rely on adhesive secretions produced
      by specialised organs, the tube feet. Adhesion is temporary and tube feet can
      also voluntarily become detached. The adhesive material is produced by two types
      of adhesive secretory cells located in the epidermis of the tube foot disc, and
      is deposited between the disc surface and the substratum. After detachment, this
      material remains on the substratum as a footprint. Using LM, SEM, and AFM, we
      described the fine structure of footprints deposited on various substrata by
      individuals of Asterias rubens. Ultrastructure of the adhesive layer of attached
      tube feet was also investigated using TEM. Whatever the method used, the adhesive
      material appeared as made up of globular nanostructures forming a meshwork
      deposited on a thin homogeneous film. This appearance did not differ according to
      whether the footprints were fixed or not, and whether they were observed hydrated
      or dry. TEM observations suggest that type 2 adhesive cells would be responsible
      for the release of the material constituting the homogeneous film whereas type 1
      adhesive cells would produce the material forming the meshwork. This reticulated
      pattern would originate from the arrangement of the adhesive cell secretory pores
      on the disc surface.

PMID- 18625323
TI  - Structures in the cell wall that enable hygroscopic movement of wheat awns.
AB  - The dispersal unit of wild wheat bears two prominent filaments called awns. The
      awns bend as they dry and straighten in a damp environment. This hygroscopic
      movement is explained by the orientation of the cellulose fibrils that build the
      cell wall, as follows. The stiff fibrils are embedded in a soft hygroscopic
      matrix. When the cell wall dries, the matrix shrinks but the fibrils do not.
      Therefore, the cell wall contracts in a direction perpendicular to the fibril
      orientation. Using X-ray scattering we identified a region at the base of the awn
      that contains fibrils aligned in all directions. This is the active part, which
      contracts as it dries and pulls the awn to a bent position. Cryo-scanning
      electron microscopy revealed sequential laminas which are rotated to form a nano
      scale plywood construction, implying planar local order within the global
      isotropy. Water molecules absorbed into the matrix probably cause large
      microscopic distortions by expanding neighboring layers in perpendicular
      directions. This is thought to cause opening of tiny gaps between fiber layers,
      to facilitate the exchange and the transport of water through the cell wall, and
      thereby to increase the sensitivity of the actuating unit to moderate changes in
      humidity.

PMID- 18625324
TI  - Shift-invariant multilinear decomposition of neuroimaging data.
AB  - We present an algorithm for multilinear decomposition that allows for arbitrary
      shifts along one modality. The method is applied to neural activity arranged in
      the three modalities space, time, and trial. Thus, the algorithm models neural
      activity as a linear superposition of components with a fixed time course that
      may vary across either trials or space in its overall intensity and latency. Its
      utility is demonstrated on simulated data as well as actual EEG, and fMRI data.
      We show how shift-invariant multilinear decompositions of multiway data can
      successfully cope with variable latencies in data derived from neural activity--a
      problem that has caused degenerate solutions especially in modeling neuroimaging
      data with instantaneous multilinear decompositions. Our algorithm is available
      for download at www.erpwavelab.org.

PMID- 18625325
TI  - The world in a river? A preliminary analysis of the 16S rDNA variability of
      Tubifex species (Clitellata: Tubificidae) from the Lambro River.
AB  - Tubifex tubifex Muller, 1774 is a cosmopolitan freshwater tubificid widely used
      as a model in ecotoxicology, population dynamics and developmental biology. It is
      traditionally recognized as a polytypic species and in Lambro River (Milano,
      Northern Italy) it occurs in two of the three recognized forms, named "tubifex"
      and "blanchardi", alternatively considered as ecological forms or distinct
      species. To investigate the genetic differentiation of the populations occurring
      in the Lambro River we sequenced a fragment of the 16S rDNA mitochondrial gene.
      T. blanchardi, characterized by a low genetic diversity, was genetically
      segregated from the other sympatric T. tubifex. The ancestral state
      reconstruction was used to define the morphological traits that support its
      distinctness. On the contrary, the other T. tubifex from the Lambro community,
      although morphologically indistinguishable, revealed an astonishing degree of
      genetic variability, both between and within the three identified clades that
      proved to be genetically isolated. Using samples from the mixed Lambro River
      community and from other countries around the world we present an overview of the
      species complex' 16S rDNA variability. Our results show that the genetic
      variability did not sensibly increase widening the data set, suggesting that the
      Lambro River populations meet the species' worldwide genetic variability.

PMID- 18625326
TI  - Incongruence in the pattern and timing of intra-specific diversification in
      bronze frogs and bullfrogs (Ranidae).
AB  - We compare patterns of lineage divergence in mitochondrial DNA (mtDNA) sequences
      of two protein-encoding mitochondrial genes (cyt b and ND2) in two ecologically
      similar, co-distributed, and closely related ranid frogs (Rana clamitans and Rana
      catesbeiana), that are geographically widespread, and frequently syntopic. We
      identified three lineages in R. clamitans, separated by 0.5% to 2.1% net
      corrected sequence divergence, comparable to two R. catesbeiana lineages
      separated by 0.6%. The geographic pattern of lineage distribution differed
      notably between the two species. In R. clamitans, we found a Coastal Plain
      Appalachian (CPA) lineage restricted to south and east of the Appalachian
      Mountains and a widespread lineage that encompassing nearly all the sampled
      range. A third distinct and divergent lineage was detected in one location in the
      southwest portion of the range (Louisiana). This pattern contrasts with the east
      west pattern in R. catesbeiana, and reflects possible differences in refugial
      dynamics and patterns of range expansion. Although both species have undergone
      range expansion and population growth, coalescent reconstruction of N(e) reflects
      larger lineages but more recent divergence in R. clamitans relative to R.
      catesbeiana, reflecting significant differences in population history or
      divergent patterns of molecular evolution at mtDNA.

PMID- 18625327
TI  - Phylogenetic relationships of leopard frogs (Rana pipiens complex) from an
      isolated coastal mountain range in southern Sonora, Mexico.
AB  - Mitochondrial DNA sequence data from the control region and 12S rRNA in leopard
      frogs from the Sierra El Aguaje of southern Sonora, Mexico, together with GenBank
      sequences, were used to infer taxonomic identity and provide phylogenetic
      hypotheses for relationships with other members of the Rana pipiens complex. We
      show that frogs from the Sierra El Aguaje belong to the Rana berlandieri
      subgroup, or Scurrilirana clade, of the R. pipiens group, and are most closely
      related to Rana magnaocularis from Nayarit, Mexico. We also provide further
      evidence that Rana magnaocularis and R. yavapaiensis are close relatives.

PMID- 18625328
TI  - BDNF reverses the CTA memory deficits produced by inhibition of protein
      synthesis.
AB  - Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis
      product that has emerged as one of the most potent molecular mediators of not
      only central synaptic plasticity, but also behavioral interactions between an
      organism and its environment. Our previous studies on the insular cortex (IC), a
      region of the temporal cortex implicated in the acquisition and storage of
      conditioned taste aversion (CTA), have demonstrated that intracortical
      microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the
      projection from the basolateral nucleus of the amygdala (Bla) to the IC of adult
      rats in vivo. Recently, we found that intracortical microinfusion of BDNF
      previous to CTA training enhances the retention of this task. In this work, we
      present experimental data showing that acute intracortical delivery of BDNF (2
      microg/2 microl per side) reverses the deficit in CTA memory caused by inhibition
      of insular cortex protein synthesis due to anisomycin administration (100
      microg/microl per side) in male adult Wistar rats. These findings suggest that
      BDNF is a protein synthesis product essential for neocortical long-term memory
      storage.

PMID- 18625329
TI  - Enhancing memory formation by altering protein phosphorylation balance.
AB  - In Lymnaea, aerial respiration can be operantly conditioned and depending on the
      training procedure employed two forms of memory can result: intermediate-term
      (ITM) and long-term memory (LTM). ITM, which persists for 3h, is dependent on de
      novo protein synthesis whilst LTM, which persists for at least 24 h, is dependent
      on both de novo protein synthesis and altered gene activity. A single 0.5 h
      training session (i.e. ITM-training) leaves behind a residual molecular memory
      trace, which a second bout of ITM-training can activate and boost it to a LTM.
      Here we extend this finding to show that either inhibiting protein phosphatase
      activity with okadaic acid (1 microM), or increasing protein kinase C (PKC)
      activity and therefore protein phosphorylation with bryostatin (0.25 ng/mL)
      treatment prior to ITM-training, results in a LTM. However, following right pedal
      dorsal 1 (RPeD1) soma ablation neither of these treatments are effective in
      producing LTM following ITM-training, indicating transcription is a necessity.
      These findings suggest that the balance between phosphorylation and
      dephosphorylation in neurons is a key factor for LTM formation.

PMID- 18625330
TI  - Mice with targeted genetic reduction of GABA(A) receptor alpha1 subunits display
      performance differences in Morris water maze tasks.
AB  - Recent research has begun to demonstrate that specific subunits of GABA(A)
      receptors may be involved in the normal expression of specific behaviors. The
      present research used mice with GABA(A) receptors whose alpha1 subunits contained
      mutations of serine 270 to histidine and leucine 277 to alanine in the TM2
      region. The purpose was an attempt to examine the possible role that this
      particular subunit may have in learning the spatial and nonspatial version of the
      Morris water maze task. Mutant animals, compared to controls, displayed elevated
      levels of pool circling in both the spatial task and the nonspatial task. These
      results suggested that normal performance of the spatial and nonspatial water
      maze tasks may be dependent upon a natural alpha1 subunit array.

PMID- 18625331
TI  - Comparison between the effects of normoxia and hypoxia on antioxidant enzymes and
      glutathione redox state in ex vivo culture of CD34(+) cells.
AB  - Hypoxia maintained biological characteristics of CD34(+) cells through keeping
      lower intracellular reactive oxygen specials (ROS) levels. The effects of
      normoxia and hypoxia on antioxidant enzymes and glutathione redox state were
      compared in this study. Hypoxia decreased the mRNA expression of both catalase
      (CAT) and glutathione peroxidase (GPX), but not affected mRNAs expression of
      superoxide dismutase (SOD). While the cellular GPX activities under hypoxia were
      apparently less than those under normoxia, neither SOD activities nor CAT
      activities were affected by hypoxia. The analysis of glutathione redox status and
      ROS products showed the lower oxidized glutathione (GSSG) levels, the higher
      reduced glutathione (GSH) levels, the higher GSH/GSSG ratios, and the less O(2)-
      and H(2)O(2) generation under hypoxia (versus normoxia). Meanwhile more primary
      CD34(+)CD38(-) cells were obtained when cultivation was performed under hypoxia
      or with N-acetyl cysteine (the precursor of GSH) under normoxia. These results
      demonstrated the different responses of anti-oxidative mechanism between normoxia
      and hypoxia. Additionally, the present study suggested that the GSH-GPX
      antioxidant system played an important role in HSPCs preservation by reducing
      peroxidation.

PMID- 18625332
TI  - Arginase modulates Salmonella induced nitric oxide production in RAW264.7
      macrophages and is required for Salmonella pathogenesis in mice model of
      infection.
AB  - Arginine is a common substrate for both inducible nitric oxide synthase (iNOS)
      and arginase. The competition between iNOS and arginase for arginine contributes
      to the outcome of several parasitic and bacterial infections. Salmonella
      infection in macrophage cell line RAW264.7 induces iNOS. Because the availability
      of l-arginine is a major determinant for nitric oxide (NO) synthesis, we
      hypothesize that in the Salmonella infected macrophages NO production may be
      regulated by arginase. Here we report for the first time that Salmonella up
      regulates arginase II but not arginase I isoform in RAW264.7 macrophages.
      Blocking arginase increases the substrate l-arginine availability to iNOS for
      production of more nitric oxide and perhaps peroxynitrite molecules in the
      infected cells allowing better killing of virulent Salmonella in a NO dependent
      manner. RAW264.7 macrophages treated with iNOS inhibitor Aminoguanidine reverts
      the attenuation in arginase-blocked condition. Further, the NO block created by
      Salmonella was removed by increasing concentration of l-arginine. The whole-mice
      system arginase I, although constitutive, is much more abundant than the
      inducible arginase II isoform. Inhibition of arginase activity in mice during the
      course of Salmonella infection reduces the bacterial burden and delays the
      disease outcome in a NO dependent manner.

PMID- 18625333
TI  - Transient oxidation as a mechanistic strategy in enzymatic catalysis.
AB  - Enzymes that employ a transient oxidation mechanism catalyze transformations that
      are overall redox neutral, but involve intermediates that have a higher oxidation
      state than the substrates or products. An oxidation/reduction sequence may be
      used directly to promote isomerization reactions or indirectly to permit the
      formation of stabilized intermediates such as carbanions. This review will focus
      on three recent examples of nicotinamide-dependent enzymes that have been found
      to employ transient oxidation during catalysis: ADP-L-glycero-D-manno-heptose 6
      epimerase, GDP-mannose 3,5-epimerase, and the 6-phosphoglucosidases from family
      4. These enzymes are remarkable in their ability to catalyze either
      nonstereospecific hydride transfers or multiple chemical steps within a single
      active site.

PMID- 18625334
TI  - Structural insights into sialic acid enzymology.
AB  - Sialic acids are a diverse family of negatively charged sugars that play
      essential biological roles. Their presence and relative abundance in different
      cells is ultimately regulated by the concerted action of a large set of enzymes.
      In this review, we focus on the most recent advances on the enzymes that govern
      sialic acid metabolism, with emphasis on structural work. Major progress has been
      made in dissecting the catalytic mechanism of sialidases, revealing a modified
      scenario of the typical glycosidase ping-pong mechanism. Similarly, X-ray
      structures of sialyltransferases uncover significant variations of formerly known
      glycosyltransferase foldings. Both sialidases and sialyltransferases seem to tell
      us that sialic acid-handling enzymes have evolved important modifications related
      to the distinctive features of sialic acid itself.

PMID- 18625336
TI  - Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation
      fascination.
AB  - Sulfotransferases and sulfatases are the major enzymes responsible for sulfate
      transfer processes. The past two years have seen the elucidation of new functions
      for these enzymes, and a great progression in their structural characterization,
      which confirms that these two types of enzymes possess a highly conserved fold.
      For catalytic activity, sulfatases must contain a formylglycine residue, which is
      generated by various formylglycine-generating enzymes. Mechanistic and structural
      details have recently been obtained for a group of cofactor-independent
      formylglycine-generating enzymes termed FGEs. Finally, an increasing light has
      been cast upon the mechanism of sulfatase inactivation by a group of clinically
      important agents, the aryl sulfamates.

PMID- 18625335
TI  - Exposing plasmids as the Achilles' heel of drug-resistant bacteria.
AB  - Many multidrug-resistant bacterial pathogens harbor large plasmids that encode
      proteins conferring resistance to antibiotics. Although the acquisition of these
      plasmids often enables bacteria to survive in the presence of antibiotics, it is
      possible that plasmids also represent a vulnerability that can be exploited in
      tailored antibacterial therapy. This review highlights three recently described
      strategies designed to specifically combat bacteria harboring such plasmids:
      inhibition of plasmid conjugation, inhibition of plasmid replication, and
      exploitation of plasmid-encoded toxin-antitoxin systems.

PMID- 18625337
TI  - Leishmania sand fly interaction: progress and challenges.
AB  - Complex interactions occurs between Leishmania parasites and their sand fly
      vectors. Promastigotes of Leishmania live exclusively within the gut, possess
      flagella and are motile, and kinesins, kinases and G proteins have been described
      that play a role in regulating flagellar assembly. Movement within the gut is not
      random: promastigotes can detect gradients of solutes via chemotaxis and
      osmotaxis. Further they use their flagella to attach to the fly midgut using
      surface glyconconjugates, a key step in establishment of the infection.
      Differentiation of mammal-infective stages is characterised by significant
      biochemical and cellular remodelling. Further, the parasites can manipulate the
      behaviour of the vector to maximise their transmission, and flies may even
      deliver altruistic apoptotic forms to aid transmission of infective stages.

PMID- 18625338
TI  - Host-microbe interactions: fungi.

PMID- 18625339
TI  - PK/PD: new insights for antibacterial and antiviral applications.
AB  - The path of new compounds from discovery to bedside is long and costly and a
      large majority of compounds never make it to the market. To improve drug
      development, better tools are needed to assess efficacy and safety early in the
      process. One approach that has been suggested by the FDA to help streamlining the
      drug development process is pharmacokinetic/pharmacodynamic (PK/PD) modeling and
      simulation. In this approach, a model-based link between PK profiles and
      corresponding PD is established. Once a suitable model is identified and
      validated, predictions about efficacy and safety of different dosing regimens can
      be made. The goal of this review is to examine the current state of PK, PD, and
      PK/PD in antibiotic and antiviral research and development.

PMID- 18625340
TI  - Src and focal adhesion kinase as therapeutic targets in cancer.
AB  - Over the past few years small molecule inhibitors of both Src family kinases and
      focal adhesion kinase (FAK) have entered clinical studies for the treatment of
      solid tumours. These adhesion-linked kinases are involved in a number of pathways
      that have impact on the behaviour of tumour cells and the challenge is now, how
      to take these forward in the clinical setting.

PMID- 18625341
TI  - Targeting TRAIL death receptors.
AB  - The natural occurring tumor necrosis factor related apoptosis-inducing ligand
      (TRAIL) induces apoptosis following binding to the two TRAIL death receptors
      (DRs). Its recombinant form and monoclonal antibodies against the TRAIL DRs
      induce cell death in a wide variety of tumor cell lines and xenografts without
      causing toxicity to normal cells and are therefore potential attractive
      anticancer agents. These agents are currently in early clinical development. The
      phase 1 and 2 studies showed until now limited toxicity and tumor responses have
      been observed. Ongoing studies focus especially on combination of these agents
      with other targeted therapies or cytotoxic therapies. In this review, we
      summarize current knowledge on these agents and highlight their potential role in
      the intrinsically chemotherapy-resistant glioblastomas. In addition, we discuss
      the mechanisms to sensitize tumors cells to rhTRAIL by combination with the
      proteasome inhibitor bortezomib.

PMID- 18625342
TI  - Application of genomics in bacterial vaccine discovery: a decade in review.
AB  - The combined power of genomics and proteomics has led to many advances in the
      discovery of bacterial vaccine targets. The 'Holy Grail' for a vaccine is to be
      pathogen specific yet conserved among all strains, so that universal coverage is
      possible with the minimal number of antigens. Genomics allows us to target
      conserved proteins, while proteomics tells us what is actually expressed and what
      is accessible to antibodies. Achievements using these latest approaches are
      exemplified by the vaccine clinical trials that are ongoing for protein targets
      against Neiserria meningitidis and Staphylococcus aureus along with promising
      discoveries that have been made for other pathogens including Streptococcus
      pneumoniae and Streptococcus pyogenes. These developments are discussed in this
      review.

PMID- 18625343
TI  - Endothelium-platelet interactions in inflammatory lung disease.
AB  - In addition to their established role in hemostasis, recent studies have
      identified platelets as key regulators of inflammatory reactions. Upon
      activation, platelets interact with both endothelial cells and circulating
      leukocytes. By receptor-mediated activation of interacting cell types and by
      release of mitogenic, pro-inflammatory and -coagulatory mediators, platelets
      contribute crucially to the initiation and propagation of pathological conditions
      and processes such as inflammatory bowel disease or atherosclerosis. In
      inflammatory lung disease, platelets play a critical role in the recruitment of
      neutrophils, eosinophils and lymphocytes as shown in experimental models of acute
      lung injury and allergic airway inflammation. Circulating platelet-leukocyte
      aggregates have been detected in patients with allergic asthma and cystic
      fibrosis, and in experimental lung injury. Here, we discuss the molecular
      mechanisms regulating the interaction of platelets with leukocytes, endothelial
      cells, and the subendothelial matrix with special regard to platelet kinetics in
      pulmonary microvessels and the putative role of platelets in inflammatory lung
      disorders. In light of the existing data from experimental and clinical studies
      it is conceivable that platelet adhesion molecules and platelet mediators provide
      promising targets for novel therapeutic strategies in inflammatory lung diseases.

PMID- 18625344
TI  - Enhancement of anti-inflammatory property of aspirin in mice by a nano-emulsion
      preparation.
AB  - Aspirin, a non-steroidal anti-inflammatory drug, widely used for its anti
      inflammatory properties is associated with several systemic side effects
      including gastro-intestinal discomfort. Inflammation can be mediated by pro
      inflammatory cytokines and, along with various other host factors eventually give
      rise to edema at the inflamed site. Because of the adverse side effects
      oftentimes associated with systemic exposure to aspirin, the aim of the present
      study was to investigate whether the anti-inflammatory property of aspirin would
      enhance if delivered as nano-emulsion preparation. Nano-emulsion preparations of
      aspirin prepared with a Microfluidizer Processor were evaluated in the croton-oil
      induced ear edema CD-1 mouse model using ear lobe thickness and the accumulation
      of specific in situ cytokines as biomarkers of inflammation. The results showed
      that particle size (90 nm) populations of nano-emulsion preparations of aspirin
      compared to an aspirin suspension (363 nm), significantly decreased (p<0. 05) ear
      lobe thickness approximately 2 fold greater than the aspirin suspension. In
      addition, the aspirin nano-emulsion further reduced the auricular levels of IL
      1alpha (-37%) and TNFalpha (-69%) compared to the aspirin suspension preparation
      (p<0.05). The reductions in ear lobe thickness were also significantly associated
      with accumulated tissue levels of IL-1alpha (r=0.5, p<0.009) and TNFalpha (r=0.7,
      p<0.0004), respectively. In conclusion, these studies indicate that a nano
      emulsion preparation of aspirin significantly improved the anti-inflammatory
      properties of an aspirin suspension in a CD-1 mouse model of induced
      inflammation.

PMID- 18625345
TI  - Effects of cystic fibrosis lung disease on gas mixing indices derived from
      alveolar slope analysis.
AB  - S(cond) and S(acin) are derived from analysis of concentration-normalized phase
      III slopes (Sn(III)) of a multiple breath inert gas washout. Studies in healthy
      and COPD subjects suggest these reflect ventilation heterogeneity in conducting
      and acinar airway zones respectively, but similar studies in cystic fibrosis (CF)
      are lacking. S(cond), S(acin) and lung clearance index (LCI, a measure of overall
      gas mixing efficiency) were measured in 22 adults and 18 children with CF and 17
      adult and 29 child controls. Plethysmography and gas transfer measurements were
      performed in adults, and spirometry in all subjects. S(cond) was elevated in
      almost all CF patients, including children with mild disease and normal LCI.
      However, S(cond) did not correlate with other measurements and appeared to reach
      a maximum; further increase in ventilation heterogeneity being restricted to
      S(acin). The nature and/or severity of CF lung disease may invalidate assumptions
      underlying the ability to separate phase III slope analysis of ventilation
      heterogeneity into proximal and peripheral components, and LCI may be a better
      indicator of gas mixing in this population.

PMID- 18625347
TI  - Indeterminate lesions in cancer imaging.
AB  - Indeterminate lesions are detected on cancer imaging examinations at all points
      along the patient pathway. Decisions made about indeterminate lesions may have
      profound impact on patient management, particularly when these may represent
      solitary sites of metastasis. In this process of decision making the radiologist,
      having detected a potential metastasis, must attempt to characterize the
      abnormality and then to make a judgement about its impact on management based on
      knowledge of the clinical context. Not every abnormality can be confidently
      characterized using the modality of detection and the indeterminate lesion may
      require further clarification through discussion in the format of a
      multidisciplinary meeting, planned further investigation, or intervention. In
      some circumstances the lesion remains indeterminate and a monitoring approach is
      appropriate. Uncertainty must not be regarded as a personal weakness of any
      individual, but may remain even after collective discussion in a
      multidisciplinary setting. The aim must be to develop a plan of action (or
      inaction) that is understandable, useful, and acceptable to the patient and
      clinician. In this review, the principles guiding these decisions are discussed
      in further detail and practical solutions to some commonly encountered
      indeterminate lesions are suggested, focusing on those that might represent
      solitary sites of disease and whose management impact may be profound.

PMID- 18625346
TI  - Mutational survey of the PHEX gene in patients with X-linked hypophosphatemic
      rickets.
AB  - X-linked hypophosphatemic rickets (XLH) is a dominantly inherited disorder
      characterized by renal phosphate wasting, aberrant vitamin D metabolism, and
      abnormal bone mineralization. XLH is caused by inactivating mutations in PHEX
      (phosphate-regulating gene with homologies to endopeptidases on the X
      chromosome). In this study, we sequenced the PHEX gene in subjects from 26
      kindreds who were clinically diagnosed with XLH. Sequencing revealed 18 different
      mutations, of which thirteen have not been reported previously. In addition to
      deletions, splice site mutations, and missense and nonsense mutations, a rare
      point mutation in the 3'-untranslated region (3'-UTR) was identified as a novel
      cause of XLH. In summary, we identified a wide spectrum of mutations in the PHEX
      gene. Our data, in accord with those of others, indicate that there is no single
      predominant PHEX mutation responsible for XLH.

PMID- 18625348
TI  - Revalidation of doctors.

PMID- 18625349
TI  - Can FDG-PET be used to predict growth of stage I lung cancer?
AB  - AIM: To determine the relationship between the metabolic activity measured by 2
      [(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) and
      computed tomography (CT)-derived tumour growth rates for stage 1 lung cancer.
      METHODS: Stage I lung cancer patients at our institution who underwent FDG PET,
      and who had at least two pre-treatment chest CT examinations (n=51), were
      retrospectively identified. Metabolic activity was defined by maximum lesion
      standardized uptake value (SUV) and maximum lesion-to-mean background activity
      (LBR). Growth rates were determined from serial CT volume measurements and the
      doubling time (DT) was calculated. Tumour growth rates were divided into rapid
      (DT<180 days), intermediate (DT=180-270 days), and slow (DT>270 days) groups.
      RESULTS: Rapid, moderate, and slow DT were seen in 22, 19, and 10 patients,
      respectively. Means (standard deviations) of SUV in the three groups (from rapid
      to slow growth rate) were 8.2 (4.8), 5.5 (4.5), and 2.2 (1.1), respectively and
      of LBR were 22.7 (10.1), 15.1 (12.6), and 6 (2.6), respectively. There was a
      significant relationship between SUV and DT (p<0.05), as well as between LBR and
      DT (p<0.05). CONCLUSIONS: For stage I lung tumours, there is a significant
      relationship between growth rates, as measured by serial CT examinations, and the
      initial pre-treatment metabolic activities, as measured by FDG uptake. This
      suggests that in patients in whom it is difficult to decide on the aggressiveness
      on treatment, FDG-PET may be used as additional prognostic tool for determining
      management.

PMID- 18625350
TI  - Embolization of renal angiomyolipoma: immediate complications and long-term
      outcomes.
AB  - AIMS: To report the outcomes of elective and emergency embolization of renal
      angiomyolipoma and describe an angiographic sign that will help localize the
      symptomatic aneurysm in emergency cases. MATERIALS AND METHODS: A retrospective
      review of all patients undergoing embolization of renal angiomyolipoma at a two
      centres between 1998-2007. Indications for treatment and angiographic images were
      reviewed. Incidence of acute rupture during embolization was noted. RESULTS:
      Seventeen patients underwent 23 episodes of embolization using polyvinyl alcohol
      (PVA) particles, bead block, and coils. Thirteen were elective procedures for
      large or symptomatic angiomyolipoma and 10 were acute procedures for patients
      presenting with retroperitoneal haemorrhage. Patients presenting acutely with
      haemorrhage tended to have extensive multifocal renal involvement. Active
      bleeding on diagnostic angiography was seen in a single patient who presented
      with retroperitoneal haemorrhage 48h after elective embolization with PVA alone.
      Seven out of 10 (70%) of the acute cases displayed splaying of adjacent vessels
      due to peri-aneurysmal haematoma, known locally as the "light bulb sign". This
      allowed treatment to be focused on the symptomatic aneurysm. The light bulb sign
      was not present in any patient undergoing elective embolization. Aneurysm rupture
      with active extravasation occurred following embolization of the distal tumour
      circulation with PVA in four of 10 (40%) of the patients in the acute group and
      three of 13 (23%) patients in the elective group. Five patients required a
      subsequent embolization, three at a different site. Two patients in the elective
      group required repeat embolization of the target site, one for delayed
      haemorrhage and the other whose tumour did not shrink following the initial
      incomplete treatment. CONCLUSIONS: Embolization of renal angiomyolipoma produces
      durable results. The presence of the light bulb sign is a strong indicator of the
      site of haemorrhage within the kidney. We advocate using a combination of
      particulate material and coils, as embolization with PVA alone may predispose to
      acute haemorrhage occurring during or after embolization.

PMID- 18625351
TI  - Value of endorectal MRI and MRS in patients with elevated prostate-specific
      antigen levels and previous negative biopsies to localize peripheral zone
      tumours.
AB  - AIM: To evaluate prospectively the role of endorectal magnetic resonance imaging
      (MRI) and magnetic resonance spectroscopy (MRS) in detecting peripheral zone
      tumour in patients with total prostate-specific antigen (PSA) values>or=4 ng/ml
      and one or more negative transrectal ultrasound (TRUS) biopsy rounds. MATERIAL
      AND METHODS: Fifty-four consecutive men (mean age 65.4+/-5.2 years, mean total
      PSA 10.8+/-7.5 ng/ml), underwent a combined MRI-MRS examination with endorectal
      coil. MRI included transverse, coronal, and sagittal T2-weighted and transverse
      T1-weighted fast spin-echo sequences. MRS data were acquired using a double spin
      echo point resolved spectroscopy (PRESS) sequence. A 10-site scheme was adopted
      to evaluate the prostate peripheral zone. A peripheral prostatic site was
      classified as suspicious if low intensity signal was present on T2-weighted
      images and/or if the choline+creatine/citrate ratio was >0.86. Following MRI-MRS
      all patients were submitted to a standard 10-core biopsy scheme to which from one
      to three supplementary samples were added from suspicious MRI and/or MRS sites.
      In per-patient analysis findings were considered true-positive if biopsy positive
      patients were classified as suspicious, irrespectively of lesion site indication.
      RESULTS: Prostate cancer (PC) was detected in 17 of 54 patients (31.5%); median
      Gleason score was 6 (range 4-8). On a per-patient basis sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV), and accuracy
      were respectively 100, 64.9, 56.7, 100, and 75.9% for MRI; 82.2, 70.3, 57.7,
      92.9, and 75.9% for MRS; and 100, 51.4, 48.6, 100, and 66.7% for combined MRI
      MRS. In all the 17 PC patients, combined MRI-MRS correctly indicated the sites
      harbouring cancer, whereas both MRI and MRS gave erroneous indications in two
      patients. CONCLUSION: The results of the present study show that MRI alone might
      be able to select negative patients in whom further biopsies are unnecessary. The
      combination of MRI and MRS might be able to drive biopsies in suspicious sites
      and increase the cancer detection rate. Further studies are required to confirm
      these data.

PMID- 18625352
TI  - Optimal contrast medium injection protocols for the depiction of the Adamkiewicz
      artery using 64-detector CT angiography.
AB  - AIM: To determine the optimal contrast medium injection protocol for
      demonstrating the Adamkiewicz artery (AKA) using 64-detector CT angiography
      (CTA). MATERIALS AND METHODS: CTA was performed using 64-detector CT. The study
      population consisted of 80 patients (mean age 67.2 years) with aortoiliac
      diseases. In the first 60 patients 540 mg I/kg body weight was administered over
      25s. The patients were randomly assigned to three protocols with imaging started
      at 15 (protocol A-1), 18 (A-2), or 21s (A-3) after triggering (threshold 150 HU).
      The other 20 received 720 mg I/kg body weight with an imaging delay of 18s
      (protocol B). Two radiologists evaluated the presence of the AKA and measured the
      attenuation of the aorta and AKA. RESULTS: Aortic enhancement was 360.4, 348,
      279.3, and 372 HU for protocols A-1, A-2, A-3, and B, respectively. There was no
      significant difference between the A-1 and A-2 protocols (Tukey-Kramer test,
      p=0.73); however, aortic enhancement was significantly lower in A-3 than A-1 and
      A-2 (p<0.01). There was no significant difference between A-2 and B (p=0.40). AKA
      attenuation was 69.3, 91.9, 94.6, and 105.4 HU for protocols A-1, A-2, A-3, and
      B, respectively. There was no significant difference between the A-2 and A-3
      protocols (p=0.91); however, AKA attenuation was significantly lower with A-1
      than A-2 or A-3 (p=0.01). AKA attenuation was significantly lower with A-2 than B
      (p=0.03) and there was a significant difference between A-2 (50%) and B (95%) in
      the depiction of the hairpin configuration of the AKA (p=0.02). CONCLUSION: For
      the demonstration of the AKA at CTA, the optimal protocol used an imaging delay
      of 18s after triggering and an iodine dose of 720 mg I/kg body weight.

PMID- 18625354
TI  - Caecal epiploic appendagitis: an unlikely occurrence.
AB  - AIM: To determine whether epiploic appendagitis occurs in the caecum. METHODS:
      From 2000-2006, 58 cases with classic computed tomography (CT) features of acute
      epiploic appendagitis (focal round or oval fat density immediately adjacent to
      the colon with surrounding oedema and stranding, with or without a central area
      of high attenuation) were identified from a radiology information system and
      available for review on the picture archiving and communication system (PACS).
      Cases were assigned to one of six colonic segments: rectum, sigmoid, descending
      colon, transverse colon, ascending colon, and caecum. The Blyth-Still-Casella
      procedure was used to derive an exact upper bound on the likelihood of epiploic
      appendagitis occurring within the caecum. RESULTS: Twenty-eight cases occurred in
      the sigmoid colon, 16 in the descending colon, four in the transverse colon, and
      10 in the ascending colon. No cases of acute epiploic appendagitis were
      identified in the caecum. Four cases of prospectively dictated caecal epiploic
      appendagitis were identified from the database. Retrospective review of these
      cases showed two cases to be epiploic appendagitis of the ascending colon. The
      third case demonstrated peritoneal thickening without evidence of an inflamed
      epiploic appendage. The fourth case was caecal diverticulitis. Based on these
      findings there is 95% confidence that no more than 4.6% of patients with epiploic
      appendagitis will show this condition within the caecum. CONCLUSION: In the
      authors' experience, epiploic appendagitis does not occur in the caecum.
      Therefore, it is an unlikely cause for an inflammatory process in this region and
      other conditions should be considered.

PMID- 18625353
TI  - The UK nephrostomy audit. Can a voluntary registry produce robust performance
      data?
AB  - AIM: To investigate the effectiveness of the Royal College of Radiologists Audit
      Sub-Committee's national prospective registry of percutaneous nephrostomy, which
      enables participants to audit their practice and compare performance with
      predetermined standards. METHODS: Following a limited retrospective audit, which
      permitted setting of achievable targets, a dataset was developed and all UK NHS
      acute hospitals were invited to participate in web-based prospective data
      collection. RESULTS: Eighty-five out of 285 (29.8%) hospitals contributed 3262
      cases over a 29 month period. A satisfactory level of performance was achieved
      with an overall technical success rate of 98% and a complication rate of 6.3%.
      Significant risk factors for complications included rigors, anaemia, and impaired
      renal function. Low frequency operators were shown to have a lower technical
      success rate and a higher complication rate than high frequency operators;
      however, target thresholds were exceeded in all groups. Sepsis was identified as
      a risk factor in the majority of serious complications and all deaths. Some
      anomalous results were found due to unusual interpretation of the data entry form
      in two centres, but no evidence of under-performance was identified at any
      centre. CONCLUSIONS: Some weaknesses of the registry are discussed. In view of
      the low response rate, the possibility of significant bias cannot be excluded. In
      addition, there is no objective verification of the data; therefore, the results
      have limited credibility. However, individual centres that accurately completed a
      representative sample of cases can have confidence that their performance
      achieves an acceptable standard.

PMID- 18625355
TI  - CT appearance of pneumatized inferior turbinate.
AB  - AIM: To study the computed tomography (CT) features of pneumatized inferior
      turbinate (PIT). MATERIALS AND METHODS: A retrospective review of paranasal sinus
      CT over a period of 12 years showed 16 cases of PIT. The pneumatization pattern
      was analysed according to the classification proposed by Bolger. Pneumatization
      was classified into three types: bulbous, lamellar, and extensive. RESULTS:
      Fourteen patients had unilateral and two patients had bilateral pneumatization
      (n=18). Seven (39%) of the 18 PIT were bulbous, nine (50%) were lamellar, and two
      (11%) were of the extensive type. In eight (44%) cases there was communication
      between the medial wall of the maxillary sinus and the PIT. CONCLUSIONS: The
      features of PIT can be readily identified on CT. Imaging helps clinicians to
      differentiate PIT from other causes of the inferior turbinate hypertrophy or
      complications.

PMID- 18625356
TI  - CT-guided sacroplasty in advanced sacral destruction secondary to tumour
      infiltration.

PMID- 18625357
TI  - Diagnosis and characterization of pulmonary sequestration using dynamic time
      resolved magnetic resonance angiography.

PMID- 18625358
TI  - The departments of radiology and anatomy: new symbiotic relations?

PMID- 18625359
TI  - Computed tomography after radical pancreaticoduodenectomy (Whipple's procedure).
AB  - Whipple's procedure (radical pancreaticoduodenectomy) is currently the only
      curative option for patients with periampullary malignancy. The surgery is highly
      complex and involves multiple anastomoses. Complications are common and can lead
      to significant postoperative morbidity. Early detection and treatment of
      complications is vital, and high-quality multidetector computed tomography (MDCT)
      is currently the best method of investigation. This review outlines the surgical
      technique and illustrates the range of normal postoperative appearances together
      with the common complications.

PMID- 18625360
TI  - Ultrasound findings of masses of the paratesticular space.
AB  - Ultrasound is a routine investigation for the assessment of scrotal masses. Many
      of the detected lesions involve the paratesticular structures. The most common
      paratesticular masses in clinical practice are epididymal cysts and
      spermatoceles, but there are a large number of other pathologies that can be
      encountered and may result in diagnostic uncertainty. This review covers a wide
      range of the common and the rare, but important, causes of paratesticular masses.
      The ultrasound findings (both typical and atypical) of these lesions are
      clarified, and emphasis is given to the features that help to differentiate
      between them.

PMID- 18625361
TI  - Imaging characteristics of common suprasellar lesions with emphasis on MRI
      findings.
AB  - Suprasellar masses are varied in aetiology and can present diagnostic problems
      for a radiologist. Magnetic resonance imaging (MRI) has largely replaced computed
      tomography (CT) as a diagnostic tool for these lesions, although CT can provide
      complementary information in some conditions. In this article, we review imaging
      features of common suprasellar lesions with emphasis on MRI features.

PMID- 18625362
TI  - A self-expandable stent overlapped with a stent-graft as a cause of endoleak in a
      patient with carotid blowout syndrome.

PMID- 18625363
TI  - Caecal metastases from cervical cancer--a rare presentation.

PMID- 18625364
TI  - Re: Spindle cell sarcoma of the profundua femoris vein, mimicking deep venous
      thrombosis.

PMID- 18625366
TI  - Re: multi-detector CT: review of its use in acute GI haemorrhage.

PMID- 18625367
TI  - Research in the Department of Pathology at the University of Utah.

PMID- 18625368
TI  - Metastatic basal cell carcinoma presenting with unilateral upper extremity edema
      and lymphatic spread.
AB  - Basal cell carcinoma (BCC), the most common human malignancy, metastasizes in
      0.0028% to 0.5% of cases, usually to the lymph nodes, lungs, bones, and skin.
      After metastatic spread of BCC, survival averages 1 to 2 years. Chemotherapy,
      radiotherapy, and surgery are treatment options. We describe metastatic basal
      cell carcinoma to the skin presenting with unilateral upper extremity edema.

PMID- 18625369
TI  - Neutrophilic dermatoses with acute myeloid leukemia associated with an increase
      of serum colony-stimulating factor.
AB  - We report a case of acute myeloid leukemia with folliculitis, Sweet's syndrome,
      and neutrophilic panniculitis after remission induction chemotherapy for acute
      myeloid leukemia. The level of endogenous granulocyte colony-stimulating factor
      was closely associated with disease activity.

PMID- 18625370
TI  - Disseminated Trichosporon inkin and Histoplasma capsulatum in a patient with
      newly diagnosed AIDS.
AB  - Histoplasma capsulatum and Trichosporon inkin may cause disseminated disease in
      immunocompromised patients. Disseminated T inkin, the causative agent of white
      piedra, is rare and difficult to diagnose. We report the case of a 28 year-old
      man with newly diagnosed HIV infection who developed asymptomatic lesions on his
      trunk and extremities. Histology demonstrated perivascular and intravascular
      budding yeasts. Blood cultures revealed fungal organisms that were difficult to
      culture. Specimens were positive for H capsulatum (confirmed by DNA probe) and T
      inkin. Compared with disseminated histoplasmosis, disseminated Trichosporon is
      relatively uncommon. Physicians should be aware of this agent in
      immunocompromised hosts.

PMID- 18625371
TI  - Central nervous system involvement in patients with mycosis fungoides and
      cutaneous large-cell transformation.
AB  - Central nervous system (CNS) involvement in mycosis fungoides (MF) is a rare
      occurrence with devastating consequences. Large-cell transformation (LCT) of MF
      is associated with a poor prognosis and increased extracutaneous manifestations.
      In this report, we present 5 patients with MF, LCT, and CNS disease to better
      define their presentation, treatment, and prognosis and present critical
      differences they have compared with their nontransformed counterparts. We found
      that patients with LCT and MF are at increased risk of CNS involvement. In
      addition, whereas patients with nontransformed MF typically have significant skin
      and visceral involvement at the time of CNS disease, some patients with LCT have
      no extracutaneous symptoms and their skin MF is in remission at the time of CNS
      presentation. Transformed patients tend to present with speech and visual
      difficulties secondary to mass lesions. Therefore, we recommend at least annual
      screening of patients with transformed MF for CNS disease with head computerized
      tomography with orbital cuts.

PMID- 18625372
TI  - Ectomesenchymal chondromyxoid tumor of the anterior aspect of the tongue.
AB  - Ectomesenchymal chondromyxoid tumor of the anterior aspect of the tongue is a
      benign rare tumor. Thirty cases have been reported so far. It presents as a
      slowly growing, asymptomatic, submucosal nodule on the anterior dorsum of the
      tongue. Histopathologically, the tumor is composed of a well-circumscribed,
      lobular proliferation of fusiform and ovoid cells in a chondromyxoid background.
      Most consistent immunohistochemical finding is the diffuse and strong
      immunoreactivity for glial fibrillary acid protein. Histogenetic origin of the
      tumor is uncertain. We report here a 56-year-old woman with a 0.7-cm tumoral
      lesion of 5 months' duration on the anterior aspect of her tongue. Total excision
      was performed and histopathologic findings were consistent with ectomesenchymal
      chondromyxoid tumor. No recurrence was observed after 2 years of follow-up.

PMID- 18625373
TI  - Interstitial granulomatous drug reaction to anakinra.
AB  - Interstitial granulomatous drug reactions are an uncommon entity presenting as
      asymptomatic, annular, erythematous to violaceous plaques. The incidence of such
      reactions has been increasing with the use of biologic agents. We report, to the
      best of our knowledge, the first such reaction to the interleukin (IL)-1
      inhibitor anakinra. Our patient presented with pink dermal plaques and nodules in
      the periaxillary region which resolved with discontinuation of anakinra and
      recurred upon restarting anakinra. Biopsy revealed a diffuse dermal infiltrate of
      lymphocytes and histiocytes with interspersed neutrophils and eosinophils.
      Fragmentation and degeneration of collagen and elastic fibers was also present.
      Withdrawal of anakinra led to complete resolution of the lesions. Interstitial
      granulomatous drug reactions are increasing in frequency and we add anakinra to
      the list of causative agents.

PMID- 18625375
TI  - Melanosis of the areola and nipple.

PMID- 18625374
TI  - Aberrant aquaporin 5 expression in the sweat gland in aquagenic wrinkling of the
      palms.
AB  - Aquagenic wrinkling of the palms (AWP) is an uncommon disease characterized by
      the rapid and transient formation of edematous whitish plaques on the palms on
      exposure to water. Although this disease is occasionally accompanied by
      hyperhidrosis, the pathophysiology of AWP remains unknown. Herein we describe a
      patient with AWP. The location of wrinkling was limited to the areas positive for
      iodine-starch test after water exposure, which suggests that AWP is etiologically
      related to hyperhidrosis. Histologic examination revealed hyperplastic and
      papillated eccrine glandular epithelium with the enlarged diameter of eccrine
      coils. Immunohistochemically, while aquaporin 5 (AQP5), one of the water channel
      AQP families, was present exclusively in the dark cells of sweat glands of
      healthy donors, an aberrant AQP5 staining, extending to the clear cells, was
      found in the patient with AWP. The hyperplastic glandular epithelium and aberrant
      AQP5 staining in the patient's sweat glands suggest that AWP stems from
      dysregulation of sweating.

PMID- 18625376
TI  - Single hippocratic (clubbed) finger revealing an underlying enchondroma.

PMID- 18625377
TI  - Fibroepithelial polyp of glans penis in a man who practiced genital hanging kung
      fu.

PMID- 18625378
TI  - Chronic cutaneous disseminated Trichosporon asahii infection in a
      nonimmunocompromised patient.

PMID- 18625379
TI  - Treatment of nephrogenic systemic fibrosis with Re-PUVA.

PMID- 18625381
TI  - Common variable immunodeficiency presenting as chronic urticaria.

PMID- 18625380
TI  - Occurrence of subacute cutaneous lupus erythematosus after treatment with
      fluorouracil and capecitabine.
AB  - Capecitabine, an oral fluoropyrimidine and 5-fluorouracil (FU) prodrug recently
      approved for the treatment of metastatic colon and breast cancer, is currently
      under investigation in patients with gastric cancer. It has the advantage of oral
      administration, and good tolerability with its activity being comparable with
      intravenous 5-FU. Lupus erythematosus and lupuslike drug eruptions have been
      observed after 5-FU treatment, but so far no cases of subacute cutaneous lupus
      erythematosus have been described in patients treated either with capecitabine or
      5-FU. We report a patient who developed subacute cutaneous lupus erythematosus
      after administration of 5-FU and capecitabine.

PMID- 18625382
TI  - A dermoscopic pitfall: ancient melanocytic nevus.

PMID- 18625383
TI  - Generalized porokeratotic eccrine ostial and dermal duct nevus associated with
      deafness.

PMID- 18625384
TI  - Worn-down nail syndrome in a child.

PMID- 18625385
TI  - Multiple penile syringomas.

PMID- 18625386
TI  - Interferon-beta injection site reaction: review of the histology and report of a
      lupus-like pattern.

PMID- 18625387
TI  - Congenital Darier disease.

PMID- 18625388
TI  - Bilateral nevus of Ito and nevus spilus in the same patient.

PMID- 18625389
TI  - Synovitis-acne-pustulosis-hyperostosis-osteitis syndrome: a dermatologist's
      diagnostic dilemma.

PMID- 18625390
TI  - Spread of cantharidin after petrolatum use resulting in a varicelliform vesicular
      dermatitis.

PMID- 18625391
TI  - Symmetrical giant facial plaque-type juvenile xanthogranuloma.

PMID- 18625392
TI  - Repigmentation of vitiligo during efalizumab.

PMID- 18625393
TI  - Dapsone-responsive histiocytoid Sweet's syndrome associated with Crohn's disease.

PMID- 18625395
TI  - Cutaneous myxoid fibroblastoma.

PMID- 18625394
TI  - Intertriginous and follicular eruption to anticytotoxic T-lymphocyte antigen 4
      monoclonal antibody.

PMID- 18625396
TI  - Treatment of extra-abdominal aggressive fibromatosis with pegylated interferon.
AB  - Aggressive fibromatosis (desmoid tumor) is a very rare neoplasm arising from the
      musculoaponeurotic structures. It is characterized by locally aggressive growth,
      and a tendency to relapse but not to metastasize. We report on a young woman with
      a large desmoid tumor of the left foot. Multiple operations and radiotherapy had
      resulted in local recurrences. Long-term immunointervention with pegylated
      interferon alfa-2b, however, led to marked clinical improvement of the patient's
      condition and a radiologically proven stabilization of the disease.

PMID- 18625397
TI  - Tubulin superfamily genes in Tribolium castaneum and the use of a Tubulin
      promoter to drive transgene expression.
AB  - The use of native promoters to drive transgene expression has facilitated
      overexpression studies in Drosophila and other insects. We identified 12 Tubulin
      family members from the genome sequence of the red flour beetle, Tribolium
      castaneum, and used the promoter from one of these to drive constitutive
      expression of a transgene. The activity of the T. castaneum alpha-Tubulin1
      (TcalphaTub1) putative promoter was pre-tested in conjunction with an eye-color
      gene, T. castaneum vermilion (Tcv), by transient expression in Tcv-deficient
      embryos. Such embryos showed complete rescue of larval eyespot pigmentation. We
      also examined the TcalphaTub1 expression pattern in germline transformants using
      the enhanced green fluorescent protein (EGFP) reporter. Beetles transformed with
      this piggyBac-based reporter ubiquitously expressed EGFP at all stages.

PMID- 18625398
TI  - Mechanisms of resistance to malathion in the medfly Ceratitis capitata.
AB  - Target site insensitivity and metabolic resistance mediated by esterases have
      been previously suggested to be involved in resistance to malathion in a field
      derived strain (W) of Ceratitis capitata. In the present study, we have obtained
      the coding sequence for acetylcholinesterase (AChE) gene (Ccace) of C. capitata.
      An allele of Ccace carrying only a point mutation Gly328Ala (Torpedo numbering)
      adjacent to the glutamate of the catalytic triad was found in individuals of the
      W strain. Adult flies homozygotes for this mutant allele showed reduced AChE
      activity and less sensitivity to inhibition by malaoxon, showing that target site
      insensitivity is one of the factors of malathion resistance. In addition, all
      individuals from the resistant W strain showed reduced aliesterase activity,
      which has been associated with specific malathion resistance in higher Diptera.
      However, the alphaE7 gene (CcalphaE7), sequenced in susceptible and resistant
      individuals, did not carry any of the mutations associated with organophosphorus
      insecticide resistance in other Diptera. Another esterase mechanism, perhaps a
      carboxylesterase selective for malathion, in addition to mutant AChE, thus
      contributes to malathion resistance in C. capitata.

PMID- 18625399
TI  - A positive feedback mechanism in the Manduca sexta prophenoloxidase activation
      system.
AB  - In Manduca sexta, pathogen recognition triggers a branched serine proteinase
      cascade which generates active phenoloxidase (PO) in the presence of a proPO
      activating proteinase (PAP) and two noncatalytic serine proteinase homologs
      (SPHs). PO then catalyzes the production of reactive compounds for microbe
      killing, wound healing, and melanin formation. In this study, we discovered that
      a minute amount of PAP1 (a final component of the proteinase pathway) caused a
      remarkable increase in PO activity in plasma from naive larvae, which was
      significantly higher than that from the same amounts of PAP1, proPO and SPHs
      incubated in vitro. The enhanced proPO activation concurred with the proteolytic
      activation of HP6, HP8, PAP1, SPH1, SPH2 and PO precursors. PAP1 cleaved proSPH2
      to yield bands with mobility identical to SPH2 generated in vivo. PAP1 partially
      hydrolyzed proHP6 and proHP8 at a bond amino-terminal to the one cut in the PAP1
      added plasma. PAP1 did not directly activate proPAP1. These results suggest that
      a self-reinforcing mechanism is built into the proPO activation system and other
      plasma proteins are required for cleaving proHP6 and proHP8 at the correct site
      to strengthen the defense response, perhaps in the early stage of the pathway
      activation.

PMID- 18625400
TI  - Drosophila odorant receptors are novel seven transmembrane domain proteins that
      can signal independently of heterotrimeric G proteins.
AB  - Olfaction in Drosophila is mediated by a large family of membrane-bound odorant
      receptor proteins (Ors). In heterologous cells, we investigated whether the
      structural features and signalling mechanisms of ligand-binding Drosophila Ors
      are consistent with them being G protein-coupled receptors (GPCRs). The detailed
      membrane topology of Or22a was determined by inserting epitope tags into the
      termini and predicted loop regions. Immunocytochemistry experiments in Drosophila
      S2 cells imply that Or22a has seven transmembrane domains but that its membrane
      topology is opposite to that of GPCRs, with a cytoplasmic N-terminus and
      extracellular C-terminus. To investigate Or signalling mechanisms, we expressed
      Or43b in Sf9 and HEK293 cells, and show that inhibitors of heterotrimeric G
      proteins (GDP-beta-S), adenylate cyclase (SQ22536), guanylyl cyclase (ODQ),
      cyclic nucleotide phosphodiesterases (IBMX) and phospholipase C (U73122) have
      negligible impact on Or43b responses. Whole cell patching of Or43b/Or83b
      transfected HEK293 cells revealed the opening of plasma membrane cation channels
      on addition of ligand. The response was blocked by lanthanum and by 2-APB, but
      not by Ruthenium red or SKF96365. Based on these data, we conclude that
      Drosophila Ors comprise a novel family of seven transmembrane receptors that in
      HEK293 cells signal by opening cation channels, through a mechanism that is
      largely independent of G proteins.

PMID- 18625401
TI  - A small deletion in the olive fly acetylcholinesterase gene associated with high
      levels of organophosphate resistance.
AB  - Organophosphate resistance in the olive fly was previously shown to associate
      with two point mutations in the ace gene. The frequency of these mutations was
      monitored in Bactrocera oleae individuals of increasing resistance. In spite of
      the difference in resistance among the individuals, there was no correlation
      between mutation frequencies and resistance level, indicating that other factors
      may contribute to this variation. The search for additional mutations in the ace
      gene of highly resistant insects revealed a small deletion at the carboxyl
      terminal of the protein (termed Delta3Q). Significant correlation was shown
      between the mutation frequency and resistance level in natural populations. In
      addition, remaining activity of acetylcholinesterase enzyme (AChE) after
      dimethoate inhibition was higher in genotypes carrying the mutation. These
      results strongly suggest a role of Delta3Q in high levels of organophosphate (OP)
      resistance. Interestingly, the carboxyl terminal of AChE is normally cleaved and
      substituted by a glycosylphosphatidylinositol (GPI) anchor. We hypothesize that
      Delta3Q may improve GPI anchoring, thus increasing the amount of AChE that
      reaches the synaptic cleft. In this way, despite the presence of insecticide,
      enough enzyme would remain in the cleft for its normal role of acetylcholine
      hydrolysis, allowing the insect to survive. This provides a previously un
      described mechanism of resistance.

PMID- 18625402
TI  - Regulation of soluble and membrane-bound trehalase activity and expression of the
      enzyme in the larval midgut of the bamboo borer Omphisa fuscidentalis.
AB  - Diapausing larvae of Omphisa fuscidentalis contain soluble and membrane-bound
      trehalase in the midgut. Soluble trehalase activity accounts for three-fourths of
      the total trehalase activity in midgut homogenates. The exposure of diapausing
      larvae to juvenile hormone analog (JHA) induced pupation, accompanied by an
      increase in soluble trehalase activity at the beginning of the prepupal period.
      Injection of 20-hydroxyecdysone (20E) increased the level of soluble trehalase
      activity 5 days postinjection in a dose-dependent manner. In contrast, no
      increase in membrane-bound trehalase activity was observed under the same
      conditions. We cloned the cDNAs that encode the soluble and membrane-bound forms
      of trehalase in O. fuscidentalis trehalase-1 (OfTreh-1) and trehalase-2 (OfTreh
      2), respectively. Treh-1 encodes a 581-aa protein while Treh-2 encodes a 648-aa
      protein with one putative transmembrane domain near the C-terminus. The mRNA
      expression level of Treh-1 was 27-fold higher than that of Treh-2 in diapausing
      larval midgut. Following the exposure of diapausing larvae to JHA, Treh-1 mRNA
      expression increased gradually until the prepupal period whereupon it increased
      dramatically; in contrast, the mRNA expression of Treh-2 remained at its initial
      level. Similarly, 20E upregulated Treh-1 expression but had no effect on Treh-2
      expression. Taken together, these results suggest that an increase in the soluble
      trehalase activity at pupation is caused by upregulation of Treh-1 gene.
      Moreover, membrane-bound trehalase does not appear to be involved in the dynamic
      changes in the hemolymph trehalose concentration that occur during the larval
      pupal transformation.

PMID- 18625403
TI  - High resistance to oxidative damage in the Antarctic midge Belgica antarctica,
      and developmentally linked expression of genes encoding superoxide dismutase,
      catalase and heat shock proteins.
AB  - Intense ultraviolet radiation, coupled with frequent bouts of freezing-thawing
      and anoxia, have the potential to generate high levels of oxidative stress in
      Antarctic organisms. In this study, we examined mechanisms used by the Antarctic
      midge, Belgica antarctica, to counter oxidative stress. We cloned genes encoding
      two key antioxidant enzymes, superoxide dismutase (SOD) and catalase (Cat), and
      showed that SOD mRNA was expressed continuously and at very high levels in
      larvae, but not in adults, while Cat mRNA was expressed in both larvae and adults
      but at a somewhat reduced level. SOD mRNA was expressed at even higher levels in
      larvae that were exposed to direct sunlight. Catalase, a small heat shock
      protein, Hsp70 and Hsp90 mRNAs were also strongly upregulated in response to
      sunlight. Total antioxidant capacity of the adults was higher than that of the
      larvae, but levels in both stages of the midge were much higher than observed in
      a freeze-tolerant, temperate zone insect, the gall fly Eurosta solidaginis.
      Assays to measure oxidative damage (lipid peroxidation TBARS and carbonyl
      proteins) demonstrated that the Antarctic midge is highly resistant to oxidative
      stress.

PMID- 18625404
TI  - RNA interference in the termite Reticulitermes flavipes through ingestion of
      double-stranded RNA.
AB  - RNA interference (RNAi) represents a breakthrough technology for conducting
      functional genomics research in non-model organisms and for the highly targeted
      control of insect pests. This study investigated RNAi via voluntary feeding in
      the economically important pest termite, Reticulitermes flavipes. We used a high
      dose double-stranded (ds) RNA feeding approach to silence two termite genes: one
      encoding an endogenous digestive cellulase enzyme and the other a caste
      regulatory hexamerin storage protein. Contrary to results from previous low-dose
      studies that examined injection-based RNAi, high-dose silencing of either gene
      through dsRNA feeding led to significantly reduced group fitness and mortality.
      Hexamerin silencing in combination with ectopic juvenile hormone treatments
      additionally led to lethal molting impacts and increased differentiation of
      presoldier caste phenotypes (a phenotype that is not capable of feeding). These
      results provide the first examples of insecticidal effects from dsRNA feeding in
      a termite. Additionally, these results validate a high-throughput bioassay
      approach for use in (i) termite functional genomics research, and (ii)
      characterizing target sites of conventional and novel RNAi-based termiticides.

PMID- 18625405
TI  - Preface: the state of the science of all motor neuron diseases.

PMID- 18625406
TI  - Foreword: motor neuron disease continues to be both a puzzle and a challenge to
      the medical community.

PMID- 18625408
TI  - Genetics of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) was first described by Charcot in 1869 as
      what we would now call a sporadic disease-a disease believed to occur without a
      strong genetic influence. Only within the past 10 years has it been possible to
      fully explore genetic influence on disorders that seem to occur sporadically but
      likely result from the convergence of multiple genetic and environmental factors.
      This article reviews the genetics of familial ALS and summarizes current
      investigations of genetic influence in sporadic ALS. Genetic study clearly offers
      the potential for identification of molecular targets that would allow
      development of rational therapies for various forms of ALS, but much work
      remains.

PMID- 18625409
TI  - Glial cells in ALS: the missing link?
AB  - Amyotrophic lateral sclerosis (ALS) was initially known as Charcot's sclerosis,
      named after the French neurobiologist and physician Jean-Martin Charcot who first
      described this type of muscular atrophy in the early nineteenth century. In the
      United States, ALS became widely known as Lou Gehrig's disease after the famous
      baseball player who succumbed to the disease in the late 1930s. Currently, ALS is
      the most common motor neuron disease, with a worldwide incidence of 8 cases per
      100,000 population per year. Familial forms constitute approximately 5% to 10% of
      all cases. Onset increases with age, with a peak in the seventh decade and a
      slight preponderance (relative risk, 1.3-1.5) among men compared with women.
      Rapid progression of motor neuron loss leads to death an average of 3 to 5 years
      after symptom onset. The cause of ALS remains unknown and there is still no
      curative therapy.

PMID- 18625411
TI  - Androgen receptor function in motor neuron survival and degeneration.
AB  - Polyglutamine repeat expansion in the androgen receptor is responsible for the
      motor neuron degeneration in X-linked spinal and bulbar muscular atrophy (SBMA;
      Kennedy's disease). This mutation, like the other polyglutamine repeat
      expansions, has proven to be toxic itself by a gain-of-function effect; however,
      a growing body of evidence indicates that loss of androgen receptor normal
      function simultaneously contributes to SBMA disease pathology, and, conversely,
      that normal androgen receptor signaling mediates important trophic effects upon
      motor neurons. This review considers the trophic requirements of motor neurons,
      focusing upon the role of known neurotrophic factors in motor neuron disease
      natural history, and the interactions of androgen receptor signaling pathways
      with motor neuron disease pathogenesis and progression. A thorough understanding
      of androgen receptor signaling in motor neurons should provide important inroads
      toward the development of effective treatments for a variety of devastating motor
      neuron diseases.

PMID- 18625410
TI  - Current and future directions in genomics of amyotrophic lateral sclerosis.
AB  - New knowledge of the structure and function of the human genome and novel genomic
      technologies are being applied to the study of sporadic amyotrophic lateral
      sclerosis (ALS). These studies can examine tens to hundreds of thousands of items
      at once, and depend on sophisticated computer processing. Current studies are
      focused on genetic susceptibility and gene expression and future studies will
      likely focus on structural variation, gene regulation and non-protein coding
      regions. The hope is that they will lead to deeper understanding of molecular
      aspects of the disease and to rational therapeutic targets.

PMID- 18625412
TI  - Designing clinical trials in amyotrophic lateral sclerosis.
AB  - Clinical trials in amyotrophic lateral sclerosis have significantly evolved over
      the last decade. New outcome measures have been developed that have reduced the
      sample size requirement as compared with survival studies. There has been
      increasing recognition that dose-ranging studies are crucial to full evaluation
      of experimental agents. While the requirements of late stage trials have not
      changed, many new designs have been suggested for earlier phase development.
      While no design achieves the perfect balance of sensitivity and efficiency,
      clinical trialists continue to work toward the goals of smaller and shorter
      trials so that more compounds can be studied concurrently.

PMID- 18625413
TI  - Motor unit number estimation in the assessment of performance and function in
      motor neuron disease.
AB  - Motor unit number estimation (MUNE) is a unique electrophysiologic test used to
      estimate the number of surviving motor units in a muscle or group of muscles. It
      is used most frequently to monitor lower motor neuron loss in amyotrophic lateral
      sclerosis and spinal muscle atrophy. Of particular interest is its use as an
      endpoint measure in clinical trials for these diseases. This article describes
      the principles of MUNE and the factors that need to be considered, and reviews
      several techniques that have been used in clinical trials and in monitoring
      progression. It then reviews experience with MUNE in clinical trials for
      amyotrophic lateral sclerosis and spinal muscle atrophy and discusses how MUNE
      correlates with measures of function.

PMID- 18625414
TI  - Fatigue in amyotrophic lateral sclerosis.
AB  - Fatigue is a common and potentially debilitating symptom of amyotrophic lateral
      sclerosis (ALS). Questionnaire studies show that ALS subjects have increased
      subjective fatigue. Physiologic studies demonstrate that ALS subjects have
      increased physical fatigue, both central and peripheral in origin. No treatment
      has been proved effective through evidence-based medicine; however, modafinil
      (Provigil) may be a helpful pharmacologic treatment. Palliative care measures,
      such as noninvasive ventilation and high-frequency chest wall oscillation, may
      also reduce fatigue.

PMID- 18625415
TI  - The role of exercise in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the
      motor nervous system. It causes progressive and cumulative physical disabilities
      in patients, and leads to eventual death due to respiratory muscle failure. The
      disease is diverse in its presentation, course, and progression. We do not yet
      fully understand the cause or causes of the disease, nor the mechanisms for its
      progression; thus, we lack effective means for treating this disease. Currently,
      we rely on a multidisciplinary approach to symptomatically manage and care for
      patients who have ALS. In this article, the authors review the literature on the
      role of exercise in patients who have ALS, and briefly compare what is known
      about exercise in other neuromuscular diseases.

PMID- 18625416
TI  - Respiratory treatment of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a progressive neurodegenerative disease with no
      known cure. The major cause of mortality and major morbidities is related to the
      effects of the disease on the muscles of the respiratory system (ie, the
      inspiratory, expiratory, and upper airway muscles). Dyspnea, swallowing
      difficulties, sialorrhea, and impaired cough are all symptoms that can be
      palliated through pharmacologic and nonpharmacologic means. Noninvasive positive
      pressure ventilation, in particular, is a technique that not only relieves
      dyspnea but may also extend the lives of patients who have this disease. It
      should be offered to all patients who have amyotrophic lateral sclerosis with a
      forced vital capacity of less than 50 percent.

PMID- 18625418
TI  - Quality of life in amyotrophic lateral sclerosis.
AB  - Although quality of life is difficult to define clearly, a number of instruments
      and questionnaires have been developed and applied to patients who have
      amyotrophic lateral sclerosis (ALS). This article reviews the spectrum of quality
      of-life questionnaires and instruments used for ALS and the data generated from
      them. It discusses positive and negative factors that can affect quality of life
      for the patient and caregiver and concludes with suggestions for ongoing
      management to enhance quality of life.

PMID- 18625419
TI  - Cognitive and behavioral impairment in amyotrophic lateral sclerosis.
AB  - Cognitive impairment in amyotrophic lateral sclerosis (ALS) is correlated with
      pathologic and radiographic changes in cerebral cortex beyond the motor regions.
      Clinically, evidence of impairment can be detected in up to 50 percent of
      patients through direct neuropsychological testing, although frank frontotemporal
      dementia (FTD) occurs in a limited percentage. Behavioral changes are also common
      and can be characterized primarily by the presence of increased apathy.
      Determining the underlying causes of cognitive or behavioral change may be
      confounded by several disease-related factors, including fatigue, respiratory
      compromise, depression, and treatment with medications such as riluzole. Studies
      assessing the evolution and relative risk for cognitive and behavioral impairment
      in ALS suggest at least two types of patients: those who have clear FTD in whom
      cognitive decline develops gradually and those who have mild cognitive or
      behavioral impairments in whom progression either does not occur or is difficult
      to detect. Limited data suggest that cognition and behavior influence compliance,
      management, and survival, although this requires further assessment.

PMID- 18625417
TI  - Nutrition and dietary supplements in motor neuron disease.
AB  - Compromised nutrition leading to weight loss is a common and significant problem
      in the amyotrophic lateral sclerosis (ALS) patient population. The benefit of
      aggressive and early nutritional therapy can profoundly influence the disease
      course, quality of life, and survival. This article reviews the role of
      nutrition, both as sustenance and treatment for patients who have ALS. Self
      medication with dietary supplements has become increasingly popular within this
      patient population. Despite their popularity, the efficacy of these compounds has
      been largely unsupported by formal clinical trials. Available data will be
      highlighted to provide a basis upon which to advise patients requesting guidance.

PMID- 18625420
TI  - The amyotrophic lateral sclerosis center: a model of multidisciplinary
      management.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating, progressive motor neuron
      disorder that poses a myriad of clinical problems. Patients who have ALS are best
      cared for in a multidisciplinary fashion, with involvement of clinicians from
      various specialties, including neurology, physical medicine and rehabilitation,
      pulmonary medicine, clinical nurse specialists or nurse practitioners, physical
      and occupational therapists, speech language pathologists, dietitians,
      psychologists, social workers, and case managers. This article provides a summary
      of the current research into the rehabilitation of ALS, including the role of
      exercise, spasticity management, mood disorders, pain, and palliative care.

PMID- 18625421
TI  - Drug therapy in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating condition characterized by
      progressive muscle wasting, inanition, respiratory failure, and death within
      approximately 2 to 5 years of onset. ALS is among the most common neuromuscular
      conditions, with an overall prevalence in the world of approximately 5 to 7
      cases/100,000 population. Epidemiologic studies have identified some potential
      risk factors for developing ALS, including a high-fat, low-fiber diet; cigarette
      smoking; slimness and athleticism; and living in urban areas. Between 5% and 10%
      of ALS is genetic, with up to 11 genetic loci identified. Although understanding
      of the pathophysiology of this disease has advanced over the past 60 years, scant
      progress has been made regarding effective treatment. The authors review the
      current understanding of the pathogenic mechanisms of ALS and approaches to
      treating the disease.

PMID- 18625422
TI  - Clinical trials in spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by
      muscle atrophy and weakness due to degeneration of the anterior horn cells in the
      spinal cord. A great need exists for an effective treatment of SMA, a disease
      that often causes severe disability in patients who are cognitively intact and
      can have a normal life expectancy. Unlike many other neurologic diseases, SMA can
      be easily diagnosed through genetic testing. Also, preclinical progress over the
      last 2 decades has been major, with the discovery of the gene and of a
      "druggable" modifying gene that provides one of several promising targets for
      treatment. SMA is rare but is a common orphan disease, so trials should be
      feasible, raising the hope that we will find effective treatments for this
      disorder.

PMID- 18625423
TI  - Diagnosis and clinical management of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease
      characterized by degeneration of lower motor neurons, with resulting progressive
      muscle weakness. The clinical phenotype and disease severity can be varied and
      occupy a wide spectrum. Although many advances have been made regarding our
      understanding of SMA, no cure is yet available. The care of patients who have SMA
      can often be complex, with many medical issues to consider. When possible, a
      multidisciplinary team approach is effective. The current understanding of SMA,
      and the clinical management and rehabilitative care of patients who have SMA, are
      discussed in this article.

PMID- 18625424
TI  - Hepatitis C virus. Preface.

PMID- 18625425
TI  - Optimizing the current therapy for chronic hepatitis C virus: peginterferon and
      ribavirin dosing and the utility of growth factors.
AB  - Achieving a sustained virologic response depends on the patient achieving three
      sequential independent milestones: virologic response, maintaining this response
      throughout treatment, and not relapsing after treatment has been completed. The
      ability to achieve these milestones depends on the doses of
      interferon/peginterferon and ribavirin used and on whether treatment with these
      medications is adjusted, interrupted, or prematurely discontinued in response to
      adverse events. This review discusses strategies to optimize peginterferon and
      ribavirin dosing and the impact that growth factors may have on the ability to
      achieve a sustained virologic response.

PMID- 18625426
TI  - Tailored treatment for hepatitis C.
AB  - Considering the high number of global cases of hepatitis C virus (HCV) infection
      (around 175 million), effective, individualized, tailored treatment approaches
      are imperative. In this respect, defining patients according to their initial
      response profiles was shown to have great impact on choosing the optimal
      treatment duration. The application of new more sensitive HCV RNA tests may
      further help to improve treatment individualization. In spite of the many
      relevant studies conducted in the past and at present, however, this problem is
      far from being resolved. Generally, it can be said that the presence of a rapid
      virologic response is a significant predictor of favorable outcome and permits an
      abbreviated treatment period. In contrast, patients who have a slow response have
      a high risk for relapse but seem to profit from extending treatment duration.
      This viral kinetically driven approach to tailor treatment is generally
      applicable to all genotypes.

PMID- 18625427
TI  - Novel hepatitis C drugs in current trials.
AB  - Almost half of the patients who have chronic hepatitis C cannot be cured with the
      current standard treatment. Recent progress in structure determination of HCV
      proteins and development of a subgenomic replicon system and a cell culture
      infectious HCV clone enabled the development of a specifically targeted antiviral
      therapy for hepatitis C (STAT-C). Many HCV-specific compounds are under
      investigation in preclinical and clinical trials. The development of agents in
      different classes may allow construction of antiviral combinations that enhance
      the effectiveness of antiviral treatment, reduce the duration of treatment, and,
      eventually, may even avoid the use of interferon-alfa.

PMID- 18625428
TI  - Noninvasive monitoring of hepatitis C fibrosis progression.
AB  - Noninvasive approaches in the diagnosis and monitoring of fibrosis are still
      evolving. Transient elastography is an inexpensive, rapid, and relatively
      accurate form of noninvasive monitoring, especially in severe fibrosis It is a
      nascent technology, however, and there is no clear indication that elastography
      is better than biopsy for less severe fibrosis. With improved resolution and
      longer term data, it may become a vital supplement. The combined use of transient
      elastography and biochemical markers seems to be the most promising noninvasive
      technique.

PMID- 18625429
TI  - Hepatitis C infection and nonalcoholic fatty liver disease.
AB  - In hepatitis C virus (HCV) infection, significant hepatic steatosis or
      superimposed nonalcoholic steatohepatitis is associated with disease severity and
      poor response to antiviral therapy. Nonalcoholic fatty liver disease (NAFLD) and
      HCV are common causes of chronic liver disease in Western countries and are
      strongly linked to concurrent obesity, insulin resistance, and the metabolic
      syndrome. With the escalating prevalence of obesity in North America, insulin
      resistance and the metabolic syndrome are major public health problems that have
      a significant impact on morbidity and mortality associated with NAFLD and HCV.
      This article focuses on the current understanding of the interplay between host
      and viral factors that are involved in the interaction between NAFLD and HCV.

PMID- 18625431
TI  - Extrahepatic manifestations of hepatitis C virus infection.
AB  - Hepatitis C virus may cause hepatic and extrahepatic diseases. Extrahepatic
      manifestations range from disorders for which a significant association with
      viral infection is supported by epidemiologic and pathogenetic data, to anecdotal
      observations without clear proof of causality. This article describes the
      diagnosis and treatment of these diseases.

PMID- 18625432
TI  - Hepatitis C and liver transplantation: enhancing outcomes and should patients be
      retransplanted.
AB  - Hepatitis C (HCV)-related end-stage liver disease is the most common indication
      for liver transplantation. Safe expansion of the donor pool with improved rates
      of deceased donation and more widespread use of living and extended criteria
      donation are likely to decrease wait list mortality. In addition, improved
      antiviral treatments and a better understanding of the delicate balance between
      under- and over-immunosuppression in this population are needed. Finally, when
      recurrent advanced fibrosis occurs, the criteria for patient selection for
      retransplantation remain widely debated. This article reviews the literature on
      these topics and the work being done in each area to maximize outcomes in
      patients receiving transplants for HCV-related cirrhosis.

PMID- 18625430
TI  - Management complexities of HIV/hepatitis C virus coinfection in the twenty-first
      century.
AB  - Because of shared routes of transmission, hepatitis C virus (HCV) coinfection is
      common among HIV-infected persons. Because of the effectiveness of antiretroviral
      therapy, chronic HCV has now emerged as a major cause of morbidity and mortality
      in this population. Because chronic HCV is highly prevalent among HIV-infected
      patients and has a rapid disease progression, antiviral therapy with pegylated
      interferon plus ribavirin is critical for the long-term survival of HIV/HCV
      coinfected patients. In this article, the authors review the (1) epidemiology of
      HCV among HIV-infected individuals, (2) effect of HIV on the natural history of
      chronic HCV, (3) impact of antiretroviral therapy on HCV coinfection, and (4)
      management of chronic HCV in the HIV-infected person.

PMID- 18625433
TI  - Hepatitis C virus infection and hepatocellular carcinoma.
AB  - Primary liver cancer is the sixth most common cancer in the world and the third
      most common cause of death attributable to cancer. Most primary liver cancers are
      hepatocellular carcinoma (HCC), accounting for 85% to 90% of cases. There is a
      trend of growing incidence of HCC in the United States. One of the most important
      risk factors for developing HCC is chronic hepatitis C virus (HCV) infection.
      Although several studies suggested the preventive effect of interferon from
      developing HCC in HCV-infected individuals, these findings need to be validated
      in large prospective and randomized trials.

PMID- 18625435
TI  - Hepatitis C virus entry and neutralization.
AB  - The processes of hepatitis C virus (HCV) entry and antibody-mediated
      neutralization are intimately linked. The high frequency of neutralizing
      antibodies (nAbs) that inhibit E2-CD81 interaction(s) suggests that this is a
      major target for the humoral immune response. The observation that HCV can
      transmit to naive cells by means of CD81-dependent and -independent routes in
      vitro awaits further investigation to assess the significance in vivo but may
      offer new strategies for HCV to escape nAbs. The identification of claudins in
      the entry process highlights the importance of cell polarity in defining routes
      of HCV entry and release, with recent experiments suggesting a polarized route of
      viral entry into cells in vitro. In this review, the authors summarize the
      current understanding of the mechanism(s) defining HCV entry and the role of nAbs
      in controlling HCV replication.

PMID- 18625434
TI  - Hepatitis C and innate immunity: recent advances.
AB  - Eradication of hepatitis C virus (HCV) infection requires a complex and
      coordinated interplay between innate and adaptive immune responses that, when it
      fails, leads to chronic infection. In this review, the innate immune mechanisms
      by which HCV is sensed and by which HCV undermines host defense are discussed.
      The critical role of dendritic cells in antigen presentation and T-cell
      activation in addition to type I interferon production and interference of HCV
      with innate immune cell functions are reviewed. Finally, current and emerging
      therapeutic approaches targeting innate immune pathways are evaluated.

PMID- 18625436
TI  - Host genetic factors and antiviral immune responses to hepatitis C virus.
AB  - Human genome variations explain some of the heterogeneity in the immune response
      to antigenic stimuli. Such differences in response to hepatitis C virus (HCV)
      antigens can account for the ability of the immune response to clear HCV after an
      acute infection or to develop more rapidly progressive liver disease. Several
      studies have examined polymorphisms in several candidate immune-response genes
      for their relation to these HCV outcomes. Results of some of these studies
      complement knowledge gained from immunology studies, and others offer new
      insights into HCV biology. This review summarizes published studies on variation
      in immune-response genes and HCV outcomes.

PMID- 18625438
TI  - Prologue to autoimmunity forum: autoimmunity reviews on redox signaling.

PMID- 18625437
TI  - Focus on FOCIS: the continuing diagnostic challenge of autosomal recessive
      chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency of defective
      neutrophil oxidative burst activity due to mutations in the genes CYBA, NCF-1,
      NCF-2, and CYBB, which respectively encode the p22-phox, p47-phox, p67-phox, and
      gp91-phox subunits. CGD usually presents in early childhood with recurrent or
      severe infection with catalase-positive bacteria and fungi. We present an unusual
      case of CGD in which Burkholderia cepacia lymphadenitis developed in a previously
      healthy 10-year-old girl. Flow cytometric analysis of dihydrorhodamine (DHR)
      labeled neutrophils performed by a CLIA-approved outside reference laboratory was
      reported as normal. However, we found that this patient's neutrophil oxidative
      burst activity in DHR assays was substantially reduced but not absent. A
      selective decrease in intracellular staining for p67-phox suggested the diagnosis
      of autosomal recessive CGD due to NCF-2 gene mutations, and a novel homozygous
      and hypomorphic NCF-2 gene mutation was found. The potential mechanisms for this
      delayed and mild presentation of CGD are discussed.

PMID- 18625439
TI  - Reactive oxygen species generation at the plasma membrane for antibody control.
AB  - Generation of reactive oxygen species (ROS) at the plasma membrane can be a
      vehicle for oxidative unmasking or masking of auto antibodies in a tissue
      selective and controlled way. There are seven related NADPH oxidases (NOX 1-5,
      DuoNOX 1,2) which can be activated in various ways to produce superoxide and
      hydrogen peroxide at the plasma membrane. There is also a plasma membrane NADH
      oxidase which is under different control. ROS can also be produced by
      mitochondria or cytosolic oxidases under special conditions. The ROS generation
      provides oxidant for thiol oxidation or peroxynitrite formation which can be a
      basis for antibody modification. The specific controls of the oxidases in
      different tissues allow a basis for localized autoantibody modification in
      response to stress or environment.

PMID- 18625441
TI  - Autoimmune thyroiditis and ROS.
AB  - Autoimmune thyroiditis, also known as chronic lymphocytic or Hashimoto's
      thyroiditis, is characterized by infiltration of the thyroid gland by
      inflammatory cells and production of autoantibodies to thyroid-specific antigens
      thyroglobulin and thyroperoxidase. It is accompanied by hypothyroidism due to
      destruction and eventual fibrous replacement of the follicle cells. Autoimmune
      thyroiditis is clearly multifactorial in etiology with genetic and environmental
      factors contributions. Excess dietary Iodine can exacerbate thyroiditis in
      genetically susceptible hosts such as the NOD.H2(h4) mouse. In this mouse excess
      dietary iodine leads to an increased immunogenicity of the thyroglobulin molecule
      and enhanced expression of ICAM-1 on thyroidal follicle cells. We present
      evidence here that ICAM-1 expression is enhanced by the elevated generation of
      reactive oxygen species (ROS). The anti-oxidant diphenyleneiodium (DPI), an
      inhibitor of NADPH oxidase, reduced both the generation of ROS and of ICAM-1
      expression in cultures of NOD.H2(h4) mouse thyrocytes. These results suggest that
      antioxidants may have therapeutic value in preventing autoimmune thyroiditis.

PMID- 18625440
TI  - Autoimmune and proinflammatory activity of oxidized immunoglobulins.
AB  - AIMS: Oxidation reactions can modify protein activity or specificity. Recently, a
      novel redox-reactive family of autoantibodies was described, which indicated
      involvement of altered antibodies (beside altered antigens) into autoimmune
      reactions. The aim of our study was to determine the binding capacity alterations
      of electro-oxidized blood donors' IgGs, and to evaluate their effects on released
      proinflammatory interleukin 6 in HUVEC. RESULTS: We found out that 1.) Isolated
      blood donor IgGs bound after electro-oxidation to beta2-glycoprotein I,
      cardiolipin, citrullinated cyclic peptide and protein 3 by enzyme-linked
      immunosorbent assay, extractable nuclear antigens by counterimmuno
      electrophoresis, and cell antigens by indirect immunofluorescence; 2.)
      Alterations in immunoreactivity of IgGs due to oxidation highly depend on
      electric current, time of exposure and the presence of antioxidants, 3.)
      Treatment of HUVEC with oxidized IgGs resulted in changed cell morphology,
      accompanied by an increase in released interleukin-6. CONCLUSIONS: Our data
      suggest repeatable transformation of antibodies present in the blood of healthy
      persons and patients. Inter-individual differences in chemical stability of
      antibodies, patient's antioxidant status, and the microenvironmental changes at
      the cellular level may influence the range of antibody alterations and their
      involvement in pathophysiological autoimmune processes.

PMID- 18625442
TI  - Immunological tolerance and the autoimmune response.
AB  - The discovery by McIntire and Faulk of masked autoantibodies calls into question
      the mechanisms of self recognition that exist in the human body. Their finding is
      reviewed in relation to three other facets of the interaction of humans with the
      foreign agencies with which they come in contact, innate immunity,
      microchimaerism and communicable disease-causing infections. It is concluded that
      the capacity to respond to foreign agencies may not primarily be defensive and
      that self recognition is probably an active process rather than dependent on
      elimination of self reactive capacity.

PMID- 18625443
TI  - Is the generation of neo-antigenic determinants by free radicals central to the
      development of autoimmune rheumatoid disease?
AB  - Biomolecules are susceptible to many different post-translational modifications
      that have important effects on their function and stability, including
      glycosylation, glycation, phosphorylation and oxidation chemistries. Specific
      conversion of aspartic acid to its isoaspartyl derivative or arginine to
      citrulline leads to autoantibody production in models of rheumatoid disease, and
      ensuing autoantibodies cross-react with native antigens. Autoimmune conditions
      associate with increased activation of immune effector cells and production of
      free radical species via NADPH oxidases and nitric oxide synthases. Generation of
      neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS)
      may contribute to epitope spreading in autoimmunity. The oxidation of amino acids
      by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS)
      increases the antigenicity of DNA, LDL and IgG, generating ligands for which
      autoantibodies show higher avidity. This review focuses on the evidence for ROS
      and RNS in promoting the autoimmune responses observed in diseases rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence
      for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or
      repair ROS/RNS damaged biomolecules and suggests that an associated defect,
      probably in T cell signal processing or/or antigen presentation, is required for
      the development of disease.

PMID- 18625444
TI  - Autoimmune mechanisms in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is perceived as a chronic immune-mediated disease with a
      subclinical prodromal period characterized by selective loss of insulin-producing
      beta-cells in the pancreatic islets in genetically susceptible subjects.
      Autoreactive T cells, both CD4 and CD8 cells, have been implicated as active
      players in beta-cell destruction. A series of autoantigens have been identified
      in T1D including insulin, glutamic acid decarboxylase (GAD), the protein tyrosine
      phosphatase-related islet antigen 2 (IA-2), and most recently the zinc
      transporter Slc30A8 residing in the insulin secretory granule of the beta-cell.
      The issue whether there is any primary autoantigen in T1D has remained
      controversial. Given that there are two major HLA haplotypes conferring disease
      susceptibility, i.e. the DR3-DQ2 haplotype and the DR4-DQ8 haplotype, one may
      assume that there will be at least two primary antigens in T1D. The first signs
      of beta-cell autoimmunity might appear already during the first year of life.
      Autoantibodies may be considered as markers of an ongoing disease process in the
      pancreatic islets, and they can be used for prediction of T1D in non-diabetic
      individuals. Autoantigen-specific T-cell responses have been detected from
      peripheral blood in both patients with T1D and in unaffected subjects, but a
      clear discrimination between diabetic and non-diabetic subjects have rarely been
      seen until recently.

PMID- 18625445
TI  - Oxidation of LDL and its clinical implication.
AB  - Oxidative modification of low-density lipoprotein (LDL) is one of the earliest
      events in atherosclerosis. Oxidized LDL (oxLDL) represents a variety of
      modification of both lipid and apolipoprotein B (apoB) components by lipid
      peroxidation. This promotes atherosclerosis through inflammatory and immunologic
      mechanisms that lead to the formation of macrophage foam cells. Recent findings
      also suggest that oxLDL forms complexes with beta(2)-glycoprotein I (beta(2)GPI)
      and/or C-reactive protein (CRP) within atherosclerotic lesions and that these
      complexes appear in the circulation. Autoantibodies (auto-Abs) against
      oxLDL/beta(2)GPI complexes occur in patients with systemic lupus erythematosus
      (SLE) and/or antiphospholipid syndrome (APS). These autoantibodies significantly
      correlate with arterial thrombosis. IgG auto-Abs having similar specificity
      emerge spontaneously in NZWxBXSB F1 mice, which generally are considered to be an
      animal model of APS, and these mice produce a monoclonal IgG auto-Ab (WB-CAL-1)
      against oxLDL/beta(2)GPI complexes. WB-CAL-1 significantly increased the in vitro
      uptake of oxLDL/beta(2)GPI complexes by macrophages, which suggests that such IgG
      auto-Abs are pro-atherogenic. In contrast, IgM anti-oxLDL natural Abs found in
      the atherosclerosis-prone mice have been proposed to be protective. The presence
      of such Abs in humans has been documented in many publications but their exact
      pathophysiological significance remains unclear. In this article, we review
      recent progress in our understanding of the clinical significance of oxidation of
      LDL, formation of oxLDL complexes, and Abs in atherosclerotic and/or autoimmune
      disease.

PMID- 18625446
TI  - Autoimmunity and oxidatively modified autoantigens.
AB  - Oxidative damage mediated by reactive oxygen species results in the generation of
      deleterious by-products. The oxidation process itself and the proteins modified
      by these molecules are important mediators of cell toxicity and disease
      pathogenesis. Aldehydic products, mainly the 4-hydroxy-2-alkenals, form adducts
      with proteins and make them highly immunogenic. Proteins modified in this manner
      have been shown to induce pathogenic antibodies in a variety of diseases
      including systemic lupus erythematosus (SLE), alcoholic liver disease, diabetes
      mellitus (DM) and rheumatoid arthritis (RA). 8-oxodeoxyguanine (oxidatively
      modified DNA) and oxidized low-density lipoproteins (LDL) occur in SLE, a disease
      in which premature atherosclerosis is a serious problem. In addition,
      immunization with 4-hydroxy-2-nonenal (HNE) modified 60 kD Ro autoantigen induces
      an accelerated epitope spreading in an animal model of SLE. Advanced glycation
      end product (AGE) pentosidine and AGE modified IgG have been shown to correlate
      with RA disease activity. Oxidatively modified glutamic acid decarboxylase is
      important in type 1 DM, while autoantibodies against oxidized LDL are prevalent
      in Behcet's disease. The fragmentation of scleroderma specific autoantigens
      occurs as a result of oxidative modification and is thought to be responsible for
      the production of autoantibodies through the release of cryptic epitopes. The
      administration of antioxidants is a viable untried alternative for preventing or
      ameliorating autoimmune disease, particularly on account of the overwhelming
      evidence for the involvement of oxidative damage in autoimmunity. However, this
      should be viewed in the light of disappointing results obtained with the use of
      antioxidants in cardiovascular disease.

PMID- 18625447
TI  - Functional variability of antibodies upon oxidative processes.
AB  - Reactive oxygen species (ROS) released from activated phagocytes are involved in
      the innate immune defense against pathogens. However, when released in excess and
      when the antioxidant systems are impaired, ROS may induce cellular and tissue
      damage and dissociation of iron ions or iron containing compounds (heme) from
      protein-bound state. Free iron ions and free heme are prooxidative.
      Immunoglobulins usually perform their biological functions at sites of
      inflammation, where they may encounter reactive oxygen species and/or redox
      active compounds. It has been demonstrated that the exposure of some antibodies
      to heme, to transition metal ions or to reactive oxygen species induces an
      appearance of new binding specificities for various autoantigens. This review
      article is devoted to the interplay between redox active agents and antibodies.
      The biological significance of the appearance of new antigen binding
      specificities on antibodies after exposure to redox-active agents is discussed.

PMID- 18625448
TI  - Novel therapeutics for Alzheimer's disease.

PMID- 18625450
TI  - Inhibition and modulation of gamma-secretase for Alzheimer's disease.
AB  - The 4-kDa amyloid beta-peptide (Abeta) is strongly implicated the pathogenesis of
      Alzheimer's disease (AD), and this peptide is cut out of the amyloid beta-protein
      precursor (APP) by the sequential action of beta- and gamma-secretases. gamma
      Secretase is a membrane-embedded protease complex that cleaves the transmembrane
      region of APP to produce Abeta, and this protease is a top target for developing
      AD therapeutics. A number of inhibitors of the gamma-secretase complex have been
      identified, including peptidomimetics that block the active site, helical
      peptides that interact with the initial substrate docking site, and other less
      peptide-like, more drug-like compounds. To date, one gamma-secretase inhibitor
      has advanced into late-phase clinical trials for the treatment of AD, but serious
      concerns remain. The gamma-secretase complex cleaves a number of other
      substrates, and gamma-secretase inhibitors cause in vivo toxicities by blocking
      proteolysis of one essential substrate, the Notch receptor. Thus, compounds that
      modulate gamma-secretase, rather than inhibit it, to selectively alter Abeta
      production without hindering signal transduction from the Notch receptor would be
      more ideal. Such modulators have been discovered and advanced, with one compound
      in late-phase clinical trials, renewing interest in gamma-secretase as a
      therapeutic target.

PMID- 18625449
TI  - Measuring target effect of proposed disease-modifying therapies in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia and is an
      increasing public health problem. Because of the severity and increasing
      prevalence of the disease in the population, it is urgent that better treatments
      be developed. Active research efforts over the past several decades have produced
      a vast knowledge base regarding AD natural history, pathology, and key biological
      mediators involved in pathogenesis. As knowledge of the biomolecular mechanisms
      of AD has increased over the past several decades, there has been a growing
      consensus on the pathophysiology of the disease. These scientific advancements
      have led to proposals for disease-modifying therapeutic interventions that
      promise to significantly alter the course of AD. The translation from preclinical
      models to human studies requires therapeutic biomarkers to increase the
      likelihood of success. This review covers the current methods and technologies
      used in the therapeutic translation of proposed disease-modifying therapies for
      AD.

PMID- 18625451
TI  - beta-Secretase as a therapeutic target for Alzheimer's disease.
AB  - beta-Secretase (memapsin 2, BACE1) is an attractive target for the development of
      inhibitor drugs to treat Alzheimer's disease (AD). Not only does this protease
      function at the first step in the pathway leading to the production of amyloid
      beta (Abeta), its gene deletion produces only mild phenotypes. In addition, beta
      secretase is an aspartic protease whose mechanism and inhibition are well known.
      The development of beta-secretase inhibitors, actively pursued over the last
      seven years, has been slow, due to the difficulty in combining the required
      properties in a single inhibitor molecule. Steady progress in this field,
      however, has brought about inhibitors that contain many targeted characteristics.
      In this review, we describe the strategy of structure-based inhibitor evolution
      in the development of beta-secretase inhibitor drug. The current status of the
      field offers grounds for some optimism, in that beta-secretase inhibitors have
      been shown to reduce brain Abeta and to rescue the cognitive decline in
      transgenic AD mice, and an orally available beta-secretase inhibitor drug
      candidate is in clinical trial. With this knowledge base, it seems reasonable to
      expect that more drug candidates will be tested in human, and then successful
      disease-modifying drugs may ultimately emerge from this target.

PMID- 18625452
TI  - New therapeutic targets in the neurovascular pathway in Alzheimer's disease.
AB  - Recent findings indicate that neurovascular dysfunction is an integral part of
      Alzheimer's disease (AD). Changes in the vascular system of the brain may
      significantly contribute to the onset and progression of dementia and to the
      development of a chronic neurodegenerative process. In contrast to the
      neurocentric view, which proposes that changes in chronic neurodegenerative
      disorders, including AD, can be attributed solely to neuronal disorder and
      neuronal dysfunction, the neurovascular concept proposes that dysfunction of non
      neuronal neighboring cells and disintegration of neurovascular unit function may
      contribute to the pathogenesis of dementias in the elderly population, and
      understanding these processes will be crucial for the development of new
      therapeutic approaches to normalize both vascular and neuronal dysfunction. In
      this review, I discuss briefly the role of vascular factors and vascular disorder
      in AD, the link between cerebrovascular disorder and AD, the clearance hypothesis
      for AD, the role of RAGE (receptor for advanced glycation end products) and LRP
      (low density lipoprotein receptor related protein 1) in maintaining the levels of
      amyloid beta-peptide (Abeta) in the brain by controlling its transport across the
      blood-brain barrier (BBB), and the role of impaired vascular remodeling and
      cerebral blood flow dysregulation in the disease process. The therapeutic
      strategies based on new targets in the AD neurovascular pathway, such as RAGE and
      LRP receptors, and on a few selected genes implicated in AD neurovascular
      dysfunction (e.g., mesenchyme homeobox gene 2 and myocardin) are also discussed.

PMID- 18625453
TI  - Targeting beta-amyloid pathology in Alzheimer's disease with Abeta immunotherapy.
AB  - More than 10 clinical trials of Abeta immunotherapy are currently underway in
      patients with Alzheimer's disease (AD). The aim is to identify safe approaches
      for the efficacious antibody-mediated removal of brain beta-amyloid or its
      neurotoxic oligomeric precursors consisting of aggregated amyloid beta-peptide
      (Abeta). Initial experimental and neuro-pathological evidence for clearance of
      brain beta-amyloid in response to Abeta immunotherapy is associated with
      structural and functional rescue of neurons, as well as initial signs of clinical
      stabilization and reduced rates of dementia progression. For the next steps in
      the future improvement of Abeta immunotherapy, major challenges in
      pharmacokinetics, safety, and tolerability need to be addressed. These include
      the low penetrations rates of IgG molecules through the blood-brain barrier,
      possible reductions in brain volume, the possibility of autoimmune disease
      related to unwanted cross-reactivity with endogenous antigens on physiological
      structures, micro-hemorrhages related to cross-reaction with pre-existing
      vascular amyloid pathology, possible relocalization of Abeta from beta-amyloid
      plaques to brain blood vessels resulting in increased amyloid angiopathy, and the
      lacking activity of Abeta antibodies on pre-existing neurofibrillary tangle
      pathology, as well as the lacking molecular identification of the forms of Abeta
      to be therapeutically targeted. The solutions to these problems will be guided by
      the fine lines between tolerance and immunity against physiological and
      pathological structures, respectively, as well as by the understanding of the
      pathogenic transition of soluble Abeta into toxic oligomeric aggregation
      intermediates in the dynamic equilibrium of beta-amyloid fibril assembly.
      Provided that the ongoing and planned clinical trials address these issues in a
      timely manner, there is a good chance for Abeta immunotherapy to be one of the
      first disease-modifying therapies of Alzheimer's disease to be introduced into
      clinical practice.

PMID- 18625454
TI  - Therapeutics for Alzheimer's disease based on the metal hypothesis.
AB  - Alzheimer's disease is the most common form of dementia in the elderly, and it is
      characterized by elevated brain iron levels and accumulation of copper and zinc
      in cerebral beta-amyloid deposits (e.g., senile plaques). Both ionic zinc and
      copper are able to accelerate the aggregation of Abeta, the principle component
      of beta-amyloid deposits. Copper (and iron) can also promote the neurotoxic redox
      activity of Abeta and induce oxidative cross-linking of the peptide into stable
      oligomers. Recent reports have documented the release of Abeta together with
      ionic zinc and copper in cortical glutamatergic synapses after excitation. This,
      in turn, leads to the formation of Abeta oligomers, which, in turn, modulates
      long-term potentiation by controlling synaptic levels of the NMDA receptor. The
      excessive accumulation of Abeta oligomers in the synaptic cleft would then be
      predicted to adversely affect synaptic neurotransmission. Based on these
      findings, we have proposed the "Metal Hypothesis of Alzheimer's Disease," which
      stipulates that the neuropathogenic effects of Abeta in Alzheimer's disease are
      promoted by (and possibly even dependent on) Abeta-metal interactions.
      Increasingly sophisticated pharmaceutical approaches are now being implemented to
      attenuate abnormal Abeta-metal interactions without causing systemic disturbance
      of essential metals. Small molecules targeting Abeta-metal interactions (e.g.,
      PBT2) are currently advancing through clinical trials and show increasing promise
      as disease-modifying agents for Alzheimer's disease based on the "metal
      hypothesis."

PMID- 18625455
TI  - Cholinergic treatments with emphasis on m1 muscarinic agonists as potential
      disease-modifying agents for Alzheimer's disease.
AB  - The only prescribed drugs for treatment of Alzheimer's disease (AD) are
      acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine, and
      tacrine) and memantine, an NMDA antagonist. These drugs ameliorate mainly the
      symptoms of AD, such as cognitive impairments, rather than halting or preventing
      the causal neuropathology. There is currently no cure for AD and there is no way
      to stop its progression, yet there are numerous therapeutic approaches directed
      against various pathological hallmarks of AD that are extensively being pursued.
      In this context, the three major hallmark characteristics of AD (i.e., the CNS
      cholinergic hypofunction, formation of beta-amyloid plaques, and tangles
      containing hyperphosphorylated tau proteins) are apparently linked. Such linkages
      may have therapeutic implications, and this review is an attempt to analyze these
      versus the advantages and drawbacks of some cholinergic compounds, such as
      acetylcholinesterase inhibitors, M1 muscarinic agonists, M2 antagonists, and
      nicotinic agonists. Among the reviewed treatments, M1 selective agonists emerge,
      in particular, as potential disease modifiers.

PMID- 18625457
TI  - 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a devastating neurological condition characterized by
      a progressive decline in cognitive performance accompanied by behavioral and
      psychological syndromes, such as depression and psychosis. The neurochemical
      correlates of these clinical manifestations now appear to involve dysfunctions of
      multiple neurotransmitter pathways. Because of the extensive serotonergic
      denervation that has been observed in the AD brain and the important role played
      by serotonin (5-HT) in both cognition and behavioral control, this
      neurotransmitter system has become a focus of concerted research efforts to
      identify new treatments for AD. 5-HT exerts its diverse physiological and
      pharmacological effects through actions on multiple receptor subtypes. One of the
      newest members of this family is the 5-HT6 receptor, a subtype localized almost
      exclusively in the CNS, predominating in brain regions associated with cognition
      and behavior. With the subsequent development of selective 5-HT6 receptor
      antagonists, preclinical studies in rodents and primates have elucidated the
      function of this receptor subtype in more detail. It is increasingly clear that
      blockade of 5-HT6 receptors leads to an improvement of cognitive performance in a
      wide variety of learning and memory paradigms and also results in anxiolytic and
      antidepressant-like activity. These actions are largely underpinned by
      enhancements of cholinergic, glutamatergic, noradrenergic, and dopaminergic
      neurotransmission, together with learning-associated neuronal remodeling. A
      preliminary report that the cognitive enhancing properties of a 5-HT6 receptor
      antagonist (namely, SB-742457) extends into AD sufferers further highlights the
      therapeutic promise of this mechanistic approach.

PMID- 18625458
TI  - Ketone bodies as a therapeutic for Alzheimer's disease.
AB  - An early feature of Alzheimer's disease (AD) is region-specific declines in brain
      glucose metabolism. Unlike other tissues in the body, the brain does not
      efficiently metabolize fats; hence the adult human brain relies almost
      exclusively on glucose as an energy substrate. Therefore, inhibition of glucose
      metabolism can have profound effects on brain function. The hypometabolism seen
      in AD has recently attracted attention as a possible target for intervention in
      the disease process. One promising approach is to supplement the normal glucose
      supply of the brain with ketone bodies (KB), which include acetoacetate, beta
      hydroxybutyrate, and acetone. KB are normally produced from fat stores when
      glucose supplies are limited, such as during prolonged fasting. KB have been
      induced both by direct infusion and by the administration of a high-fat, low
      carbohydrate, low-protein, ketogenic diets. Both approaches have demonstrated
      efficacy in animal models of neurodegenerative disorders and in human clinical
      trials, including AD trials. Much of the benefit of KB can be attributed to their
      ability to increase mitochondrial efficiency and supplement the brain's normal
      reliance on glucose. Research into the therapeutic potential of KB and ketosis
      represents a promising new area of AD research.

PMID- 18625456
TI  - Tau-based treatment strategies in neurodegenerative diseases.
AB  - Neurofibrillary tangles are a characteristic hallmark of Alzheimer's and other
      neurodegenerative diseases, such as Pick's disease (PiD), progressive
      supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal
      dementia and parkinsonism linked to chromosome 17 (FTDP-17). These diseases are
      summarized as tauopathies, because neurofibrillary tangles are composed of
      intracellular aggregates of the microtubule-associated protein tau. The molecular
      mechanisms of tau-mediated neurotoxicity are not well understood; however,
      pathologic hyperphosphorylation and aggregation of tau play a central role in
      neurodegeneration and neuronal dysfunction. The present review, therefore,
      focuses on therapeutic approaches that aim to inhibit tau phosphorylation and
      aggregation or to dissolve preexisting tau aggregates. Further experimental
      therapy strategies include the enhancement of tau clearance by activation of
      proteolytic, proteasomal, or autophagosomal degradation pathways or anti-tau
      directed immunotherapy. Hyperphosphorylated tau does not bind microtubules,
      leading to microtubule instability and transport impairment. Pharmacological
      stabilization of microtubule networks might counteract this effect. In several
      tauopathies there is a shift toward four-repeat tau isoforms, and interference
      with the splicing machinery to decrease four-repeat splicing might be another
      therapeutic option.

PMID- 18625460
TI  - Biochemical studies of the maturation of herpesvirus nucleocapsid species.
AB  - Three distinct species of nucleocapsids of equine herpesvirus type-1, designated
      as either light (L), intermediate (I), or heavy (H) on the basis of their
      densities in Renografin-76 density gradients (Perdue et al. 1975), were
      characterized with respect to their amino acid content, DNA content, and role in
      the maturation process. Preparations of L and I nucleocapsids, shown previously
      to lack a densely staining core within the capsid, exhibited virtually identical
      amino acid compositions. Preparations of H nucleocapsids, which possess densely
      staining cores, contained significantly more lysine, glutamic acid, and serine
      than did L and I capsids and, in general, more closely resembled the enveloped
      virion in amino acid composition. The increased content of lysine and glutamic
      acid in H nucleocapsids indicates that polypeptide IVa (30,000 mol wt), which is
      present only in H nucleocapsids, is rich in these amino acids. These amino acids
      may be present as polylysine and polyglutamic acid which have been shown to
      collapse DNA and function in the DNA packaging event of bacterial viruses
      (Laemmli, 1975). DNA isolated from preparations of each of the three nucleocapsid
      species was characterized and shown to be identical to the DNA of enveloped virus
      in density (1.716 g/cm(3)) and size (50-55 S). The intranuclear production of the
      three nucleocapsid species was studied with respect to both the time and rate of
      synthesis of each and the relative amount of each species present during
      infection. All three species appeared at 6-8 hr postinfection and were produced
      in a logarithmic fashion until 15 hr postinfection. The ratio of L:I:H particles,
      based on the percentage that each species comprised of the total purified
      nucleocapsid population, remained constant and was approximately 45:45:10 at all
      times postinfection. Analysis of the fate of each of the three intranuclear
      nucleocapsid classes by pulse-chase experiments indicated that I and H species
      are removed from the nucleus by participation in the maturation process, but L
      capsids remain in the nucleus throughout infection and are defective by-products
      of virus assembly. Based on the evidence accumulated in this study and on
      previous data (Perdue et al. 1974, 1975), a model depicting equine herpesvirus
      maturation is proposed. This model proposes that the viral DNA is inserted into I
      nucleocapsids and that this process is accompanied by condensation of the
      internal protein resulting in the formation of a dense core and hence an H
      nucleocapsid.

PMID- 18625461
TI  - Complexity of EBV homologous DNA in continuous lymphoblastoid cell lines.
AB  - The complexity of Epstein-Barr Virus (EBV) homologous DNA in 11 EBV-infected
      lymphoblastoid cell lines which have been passaged for several years in culture
      was determined by hybridization of lymphoblastoid cell DNA to DNA extracted from
      EBV purified from HR-1 cells and labeled in vitro. Five of the cell lines
      analyzed contained no early (EA) or viral capsid (VCA) antigens which have been
      associated with the replication of EBV. Two other cell lines contained EA but not
      VCA. Of the seven VCA-negative cell lines, those which contained some early
      antigen or in which early antigen could be induced with IUDR had 56, 48, and 25
      copies per diploid cell genome of more than 90% of the sequences of EBV DNA. Five
      cell lines which did not contain EA even after induction had 23, 8, 8, 6, and 2
      copies per cell of the EBV genome. The data indicate that there is a correlation
      between the number of copies of EBV DNA in nonpermissive cells and the ability of
      these cells to express EA. Three of the five EA and VCA negative nonpermissive
      cell lines contained DNA homologous to more than 90% of the sequences of EBV DNA.
      The kinetics of hybridization of the DNA of two other nonpermissive cell lines,
      Namalwa and SKL, which contain two and eight copies, respectively, of some EBV
      DNA sequences, suggest but do not prove that these cell lines may contain
      incomplete viral genomes. The retention of the full complexity of viral DNA in
      most nonpermissive lymphoblastoid cell lines may be related to the relatively
      large number of copies of the viral genome in these cells.

PMID- 18625462
TI  - Physical map of bacteriophage phi29 DNA.
AB  - Restriction endonuclease EcoRI cleaves linear phi29 DNA at four points yielding
      five fragments (A-E) of molecular weights 6.0 x 10(6), 3.8 x 10(6), 1.3 x 10(6),
      0.6 x 10(6), and 0.3 x 10(6). The relative order of the fragments was shown to be
      A, B, E, D, C by analysis of the EcoRI partial digestion products and from the
      study of the fragments obtained by treatment of protein-containing DNA with EcoRI
      and trypsin. The EcoRI cleavage map of phi29 DNA has been ordered relative to the
      genetic map by marker rescue experiments.

PMID- 18625463
TI  - Electron microscopy of mammalian type-C RNA viruses: use of conditional lethal
      mutants in studies of virion maturation and assembly.
AB  - Mouse embryo cultures infected with each of a number of physiologically-distinct
      temperature-sensitive mutants of R-MuLV were examined by electron microscopy in
      an attempt to further define the replication defects of these mutants at the
      nonpermissive temperature (39 degrees ). Three mutants, ts24, ts25, and ts26,
      previously shown to be defective in postintegration steps, have been divided into
      two distinct subclasses. Mutants ts25 and ts26 synthesize viral antigens, but do
      not assemble viral particles at the nonpermissive temperature, whereas in mutant
      ts24 infected cells, particles at a late stage of budding were observed at very
      high frequency. An additional R-MuLV mutant, ts29, previously found to possess an
      early replication block associated with a thermolabile reverse transcriptase was
      shown to possess a second replication defect involving a very early stage of
      virus assembly. By examination of ts mutant infected cultures at various times
      following shift to their permissive temperatures partial synchronization was
      achieved with a high proportion of immature virions observed at similar stages of
      maturation. These findings more precisely define the stages of replication at
      which selected R-MuLV ts mutants are blocked at their nonpermissive temperatures,
      and illustrate the potential value of conditional lethal replication mutants for
      studies of type-C RNA virus maturation and assembly.

PMID- 18625464
TI  - The isolation of suppressible nonsense mutants of bacteriophage phi6.
AB  - Nonsense mutants of bacteriophage phi6 have been isolated and characterized.
      Eight classes have been identified involving 9 of the 12 proteins whose synthesis
      is directed by the virus. Pleiotropic effects have been observed among the mutant
      types. Mutants of class 1 and class 2 which affect proteins Pi and P2,
      respectively, direct the synthesis of only early proteins in nonsuppressor cells,
      indicating that these two proteins are involved in the transition from early to
      late viral protein synthesis. Polar effects are observed in several mutant
      classes. Virus containing a nonsense mutation in the gene for P8 does not direct
      the synthesis of P12 in nonsuppressor cells, whereas several mutants defective in
      the synthesis of P12 do cause the synthesis of P8. Similarly, cells infected with
      mutants that are defective in P9 also lack P5 and P11, while those infected with
      virus defective in P5 and P11 synthesize normal amounts of P9. A situation of
      reciprocal polarity exists between P3 and P6 in which the lack of production of
      either protein results in the reduced synthesis of the other. Evidence is
      presented indicating that the pair of proteins P5 and P11 are derived from a
      common precursor and that P5 is a cleavage product of P11.

PMID- 18625459
TI  - PPARgamma agonists as therapeutics for the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid
      within the brain parenchyma and is accompanied by the impairment of neuronal
      metabolism and function, leading to extensive neuronal loss. The disease involves
      the perturbation of synaptic function, energy, and lipid metabolism. The
      development of amyloid plaques results in the induction of a microglial-mediated
      inflammatory response. The nuclear receptor peroxisome proliferator-activated
      receptor gamma (PPARgamma) is a ligand-activated transcription factor whose
      biological actions are to regulate glucose and lipid metabolism and suppress
      inflammatory gene expression. Thus, agonists of this receptor represent an
      attractive therapeutic target for AD. There is now an extensive body of evidence
      that has demonstrated the efficacy of PPARgamma agonists in ameliorating disease
      related pathology and improved learning and memory in animal models of AD. Recent
      clinical trials of the PPARgamma agonist rosiglitazone have shown significant
      improvement in memory and cognition in AD patients. Thus, PPARgamma represents an
      important new therapeutic target in treating AD.

PMID- 18625471
TI  - The polypeptides of adenovirus. IX. Partial purification of early proteins and
      observations on late proteins of type 5 adenovirus.
AB  - The identification and partial purification of adenovirus type 5 (Ad5)-induced
      early proteins were achieved. Mock- and virus (high multiplicity)-infected HeLa
      cells were labeled for 90 min with [35S]- or [3H]methionine at 5 hr after
      infection in the presence of cytosine arabinoside. Labeled polypeptides from
      these cells were sequentially fractionated with a four-step extraction procedure:
      (1) 10 mM NaCl, (2) 1.7 M NaCl, (3) 2% Triton X-100, and (4) 6 M urea plus 2%
      Triton X-100. At each step, polypeptides from mock-infected and infected cell
      fractions were analyzed by DEAE-Sephadex chromatography and sodium dodecyl
      sulfate-polyacrylamide-gel electrophoresis (SDS-disc-PAGE) followed by
      autoradiography. Six virus-induced early proteins were discerned: El, 42K (E1A),
      E2, E2A, E2B, and E3. Polypeptides of Ad5 virions and top components and
      polypeptides induced at the late stage of adenovirus type 5 infection were
      analyzed by SDS-PAGE. They were similar to the polypeptide constituents of
      adenovirus type 2 (Ad2), except that the hexon and fiber of type 5 had mobilities
      in polyacrylamide (PA) different from those of type 2. The results eliminate the
      possibility that polypeptides taking part in Ad5 morphogenesis differ greatly
      from those of Ad2.

PMID- 18625472
TI  - Virus-specific RNA species present in the cytoplasm of Rous sarcoma virus
      infected chicken cells.
AB  - Polyadenylated and nonpolyadenylated cytoplasmic RNA from chicken cells infected
      with wild-type (wt) and transformation-defective (td) Rous sarcoma virus (RSV)
      were fractionated on sucrose density gradients and hybridized with a [3H]cDNA
      probe complementary to RSV-RNA to determine the size distribution of virus
      specific RNA. Two major species of poly (A) -containing viral RNA sedimenting at
      35 and 21 S were detected in wt and td virus-infected cells. Both RNA classes
      were released from polyribosomes with puromycin, suggesting that each RNA species
      serves as messenger in vivo. Another minor size class of virus-specific RNA, 10
      12 S, was found in both the polyadenylated and nonpolyadenylated RNA fractions.

PMID- 18625473
TI  - The distribution of virus-specific RNA in Rous sarcoma virus-induced hamster
      tumor cells.
AB  - Poly(A)-containing cytoplasmic RNA and nuclear RNA from Rous sarcoma virus (RSV)
      induced hamster tumor cells was fractionated on sucrose density gradients and
      hybridized with a [3H]cDNA probe to determine the size distribution of virus
      specific RNA. One size class of viral RNA sedimenting at 21 S was detected in
      cytoplasmic poly(A)-containing RNA. Nuclear RNA contained three species of virus
      specific RNA sedimenting at 47, 35, and 21 S. Sedimentation of nuclear RNA under
      denaturing conditions did not change this size distribution.

PMID- 18625474
TI  - Circular adenovirus DNA-protein complexes from infected HeLa cell nuclei.
AB  - Adenovirus (Ad) DNA was extracted by the use of Sarkosyl from Ad5-infected HeLa
      cell nuclei at 15 hr after infection. Mature and replicating viral DNA molecules
      in the Sarkosyl extract were purified by sucrose gradient centrifugation followed
      by equilibrium centrifugation in preformed metrizamide gradients. Part of the
      material was digested with the Hpa I restriction endonuclease and analyzed by
      electrophoresis through 1% agarose gels. Both terminal fragments D and E did not
      enter the gel unless first treated with Pronase, suggesting that intracellular
      viral DNA molecules were linked to proteins by their termini. Examination under
      the electron microscope of mature intracellular Ad2 or Ad5 DNA molecules
      extracted with Sarkosyl showed the presence of a majority of circular unit-length
      molecules. Most of these were attached to a prominent globular structure which
      disappeared, together with the circularization of the molecule, after treatment
      with Pronase. We interpret these structures as protein links responsible for the
      circularization of the molecule. The mature linear DNA molecules observed also
      showed evidence for linkage structures attached to one or both of their ends.
      Examination of replicating Ad5 DNA molecules extracted with Sarkosyl revealed the
      presence of various types of forked, circular molecules, most of which showed
      evidence for the presence of linkage structures. It is suggested that replicating
      and newly made Ad DNA molecules are circular inside the cell, perhaps through
      linkage with proteins, and the possible role of circularization in the
      replication of viral DNA is discussed.

PMID- 18625475
TI  - Mechanism of interferon action. Kinetics of interferon action in mouse L929
      cells: translation inhibition, protein phosphorylation, and messenger RNA
      methylation and degradation.
AB  - The effect of the duration of interferon treatment of mouse L929 fibroblasts on
      the expression of ribosome-associated and cell-sap-localized translation
      inhibition, protein phosphorylation, and messenger RNA (mRNA) methylation and
      degradation was investigated. The following results were obtained: (1) Ribosomal
      salt-wash fractions prepared from L929 cells treated for 12 or 18 hr
      significantly inhibited the translation of methylated reovirus mRNA catalyzed by
      the cell-free system prepared from untreated ascites tumor cells. The translation
      of reovirus mRNA was slightly stimulated by the ribosomal salt-wash fractions
      prepared from untreated cells and cells treated for 2 hr and was slightly
      inhibited by the salt-wash fraction from cells treated for 6 hr. (2) Cell-sap
      fractions prepared from untreated cells and from cells treated for 2 or 6 hr did
      not appreciably affect the translation of reovirus mRNA in the absence of double
      stranded RNA (dsRNA); cell-sap fractions prepared from cells treated for 12 or 18
      hr were slightly inhibitory. (3) Neither reovirus genome dsRNA nor
      polyriboinosinic acid-polyribocytidylic acid inhibited the translation of
      reovirus mRNA by the untreated ascites system. The inhibitory activity of
      ribosomal salt-wash fractions from interferon-treated cells was dsRNA
      independent, whereas dsRNA enhanced the inhibitory activity of cell-sap fractions
      from interferon-treated cells. (4) Interferon treatment significantly enhanced a
      cell-sap-independent phosphorylation of at least three proteins present in the
      ribosomal salt-wash fractions. Phosphorylation of an approximately 50,000-dalton
      component was maximally enhanced after 12 hr of interferon treatment and was
      increased by dsRNA; phosphorylation of 30,000- and <20,000-dalton components was
      enhanced earlier and was dsRNA independent. (5) An increase in the nuclease
      mediated degradation of [3H]uridine-labeled methylated reovirus mRNA catalyzed by
      ribosomal salt-wash fractions was detectable after 6 hr of interferon treatment
      and was maximally enhanced after 12 hr of interferon treatment to about threefold
      the level of the untreated ribosomal salt-wash fraction. The degradation was not
      enhanced by dsRNA. The levels of reovirus mRNA degradation catalyzed by cell-sap
      fractions from untreated cells and from cells treated with interferon for 2 to 18
      hr were comparable. (6) No significant difference was observed in the ability of
      cell-sap fractions from untreated cells or from cells treated with interferon for
      2 to 18 hr to catalyze the methylation of unmethylated reovirus mRNA. In
      addition, none of the ribosomal salt-wash fractions significantly inhibited
      reovirus mRNA methylation catalyzed by untreated ascites cell-free extracts.
      These results suggest that interferon treatment may mediate multiple biochemical
      changes in murine cells, including the specific phosphorylation of protein(s)
      associated with ribosomes that possess interferon-mediated inhibitor(s) of viral
      mRNA translation.

PMID- 18625476
TI  - Gene order of the mouse mammary tumor virus glycoproteins.
AB  - Immunochemical and tryptic peptide mapping techniques were used to show that the
      mouse mammary tumor virus (MMTV) envelope glycoproteins gp52 and gp36 are
      distinct components derived from a common glycosylated precursor polypeptide of
      75,000 daltons (gPr75). Because both gp52 and gp36 are derived from a common
      precursor polypeptide and therefore have a common initiation site, we have been
      able to determine their gene order within the viral genome. The gene order was
      deduced from three different types of experiments. The first approach measured
      the differential inhibition by NaCl hypertonic shock on initiation of gp52 and
      gp36 synthesis. The second approach measured the kinetics of appearance of
      various MMTV proteins following the synchronized reinitiation of polypeptide
      synthesis resulting from NaCl hypertonic shock. The third approach analyzed
      polypeptides released from polyribosomes after a series of variable-length short
      pulses with [3H]amino acids. Our results indicate that the gene order for gPr75
      is H2N-gp52-gp36-COOH and 5'-gp52-gp36-3' within the MMTV genome.

PMID- 18625477
TI  - Structural proteins of Tacaribe and Tamiami virions.
AB  - Tacaribe and Tamiami viruses were grown in BHK-21 monolayers and purified by
      centrifugation in combination glycerol-tartrate gradients followed by sucrose
      gradient centrifugation. The major polypeptides of Tacaribe and Tamiami virions
      were shown to differ from those of Pichinde virions when suitably labeled
      preparations of the three viruses were coelectrophoresed in SDS-polyacrylamide
      gels. Tacaribe and Tamiami virions each contained two major polypeptides, a
      nonglycosylated protein of molecular weight 68,000 and 66,000, respectively, and
      a single glycoprotein size-class of molecular weight 42,000 and 44,000,
      respectively. The nonglycosylated protein is associated with the viral RNA in a
      nucleoprotein structure which can be isolated by equilibrium centrifugation in
      CsCl. The glycoproteins were selectively removed from virions by chymotrypsin
      treatment, which produces essentially spikeless particles. Tacaribe and Tamiami
      virions also contain a minor polypeptide species of molecular weight 79,000 and
      77,000, respectively.

PMID- 18625478
TI  - In vitro transformation with avian myelocytomatosis virus strain CMII:
      characterization of the virus and its target cells.
AB  - Avian myelocytomatosis virus strain CMII induced an in vitro transformation in
      cells from various hematopoietic tissues and could be quantitated by focus and
      soft agar colony assay techniques. The CMII-transformed bone marrow cells had a
      high proliferative capacity in comparison to uninfected controls. The cells
      closely resembled hematopoietic cells transformed by strain MC29 myelocytomatosis
      virus, but differed from avian myeloblastosis virus (AMV)-transformed cells. They
      were phagocytic, became adherent under certain conditions of culturing, and
      required colony-stimulating factor for colony formation in semisolid medium.
      These properties are characteristic for cells of the granulocyte/macrophage
      lineage of differentiation. In contrast to avian erythroblastosis virus, CMII
      effectively transformed macrophage cultures suggesting that the target cell
      belongs to the corresponding differentiation lineage. That it is not identical to
      normal granulocyte/macrophage colony-forming cells was demonstrated by cell
      separation experiments. In addition to hematopoietic cells, CMII induced a
      morphological transformation in chicken fibroblasts. CMII was found to consist of
      a mixture of a transforming component and an associated nontransforming virus of
      subgroup B or D. The transforming component is defective for replication and
      could be complemented by standard helper viruses of subgroups B, C, and D.

PMID- 18625479
TI  - In vivo transcription on oligomeric simian virus 40 (SV40) DNA.
AB  - A simian virus 40 nucleoprotein complex containing an endogenous RNA polymerase
      activity was extracted from infected BSC-1 nuclei with Triton X-100 in low ionic
      strength buffer. About 30% of both SV40 DNA and total SV40 transcriptional
      activity in isolated nuclei are recovered by this procedure. When the
      nucleoprotein complexes are labeled in vitro with [32P] UTP followed by
      sedimentation in neutral sucrose gradients containing Sarkosyl, labeled RNA is
      detected as a broad band extending from 21 S to more than 50 S with a major peak
      at 26 S. After treatment of the labeled complexes with pancreatic ribonuclease, 5
      to 8% of the labeled RNA remains associated with the template DNA. The majority
      of the ribonuclease-resistant material sediments slightly faster than SV40 DNA I.
      The partially relaxed SV40 DNA I associated with this material represents the
      predominant template DNA for late SV40 transcription (Birkenmeier et al., 1977).
      The remainder of the ribonuclease-resistant material sediments in sucrose
      gradients in a series of faster-sedimenting peaks. The identification of these
      structures as closed circular oligomeric SV40 DNA molecules that are serving as
      templates for transcription is based on their sedimentation rates, the time of
      their accumulation during the lytic cycle, their migration in agarose gels, and
      their appearance in the electron microscope. At late times after infection at
      least 10% of the total SV40 template DNA is in the forms of oligomers. The
      possible correlation between those findings and the presence of high molecular
      weight virus-specific RNA is discussed.

PMID- 18625480
TI  - Envelope and nucleoid ultrastructure of Molluscum contagiosum virus.
AB  - The ultrastructure of the mature and immature poxvirus Molluscum contagiosum has
      been examined by electron microscopy. With freeze-fracturing one fracture plane
      was observed in the viral envelope. During the conversion of immature into mature
      virus, particles inside the envelope become partly rearranged into parallel
      bands. Depressions in freeze-fractured cores of mature particles suggest the
      presence of water-rich regions. The organization of the nucleoid was investigated
      by thin sections analyzed in a tilting rotating specimen stage. The nucleoid
      consists of fibers with a diameter of approximately 10 nm which are probably
      connected to each other, thus forming one long fiber. In thin sections four
      profiles of the nucleoid were observed which were transformed into one another by
      tilting. Serial sections together with tilting revealed a twist of about 180
      degrees between the fibers of the two lobules of the nucleoid. A model for the
      conformation of the nucleoid in the mature brickstone particles is presented.

PMID- 18625481
TI  - Partial characterization of the proteins of human papilloma viruses (HPV) 1-3.
AB  - The protein compositions of full and empty particles of human papilloma viruses
      1, 2, and 3 were compared by SDS-gel electrophoresis. The protein patterns
      revealed a considerable variation in the relative concentrations of three major
      proteins (VP2, 3, and 4) in individual preparations. In some cases, "heavy" and
      "light" full particles prepared from the same wart showed a similar variability
      in the concentrations of VP2, 3, and 4. The different protein patterns were
      interpreted as resulting from conversion of VP2 into VP3 and 4. The molecular
      relationship of these three proteins was confirmed by BrCN cleavage which led to
      corresponding oligopeptides. Electron micrographs of empty particles revealed
      that the only detectable protein components VP3 and 4 are present in typical
      capsomeres.

PMID- 18625482
TI  - Characterization of type C virus induction by amino acid analogs.
AB  - Several amino acid analogs were tested for their ability to induce type C virus
      from a cloned Balb/c mouse cell line transformed by Kirsten sarcoma virus. O
      Methylthreonine and hydroxynorvaline, analogs of isoleucine and threonine,
      respectively, were found to induce type C virus with the host range of Balb:virus
      2. Type C virus was also activated by lysine deprivation. When either O
      methylthreonine or hydroxynorvaline was used in conjunction with the arginine
      analog canavanine, the induction equalled or surpassed the maximum induction by
      cycloheximide. Using synchronized cells, induction of virus by canavanine was
      found to be cell-cycle dependent. Depriving cells of certain single amino acids
      alone or in combination with specific analogs markedly reduced protein synthesis
      without inducing virus. The results suggest that a general reduction in protein
      synthesis cannot account for the induction and imply that the inducing analogs
      may affect the functionality or degradation of proteins involved in the
      regulation of virus expression.

PMID- 18625483
TI  - Block to influenza virus replication in cells preirradiated with ultraviolet
      light.
AB  - Ultraviolet (uv) irradiation of CEF cells immediately before infection with
      influenza A (fowl plague) virus inhibited virus growth; no inhibition of the
      growth of a parainfluenza virus (Newcastle disease virus) could be detected in
      irradiated cells. The kinetics of inhibition after various doses of uv
      irradiation were multihit, with an extrapolation number of two. When irradiated
      cells were allowed to photoreactivate by exposure to visible light for 16 hr
      their capacity to support influenza virus replication was largely restored; this
      process was sensitive to caffeine, suggesting that it required DNA repair. In CEF
      cells exposed to 360 ergs/mm(2) of uv radiation the rate of synthesis of host
      cellular RNA was reduced by more than 90%, and that of host cellular protein by
      40-50%, as judged by incorporation of precursor molecules into an acid-insoluble
      form. When such irradiated cells were infected with influenza virus all the
      genome RNA segments were transcribed, but the overall concentration of virus
      specific poly (A)-containing cRNA was reduced about 50-fold. Within this
      population of cRNA molecules, the RNAs coding for late proteins (HA, NA, and M)
      were reduced in amount relative to the other segments. The rates of synthesis of
      the M and HA proteins were specifically reduced in uv-irradiated cells, but the
      rates of synthesis of the P, NP, and NS proteins were only slightly reduced
      compared to normal cells. Immunofluorescent studies showed that, in uv-irradiated
      cells, NP migrated into the nucleus early after infection and later migrated out
      into the cytoplasm, as in normal cells. In contrast to normal cells, no specific
      immunofluorescence associated with M protein could be observed in uv-irradiated
      cells. It is concluded that uv-induced damage to host cellular DNA alters the
      pattern of RNA transcription in CEF cells infected with influenza virus, and that
      this results in a block to late protein synthesis which stops virus production.

PMID- 18625484
TI  - Immunologic characterization of gp70 and gp45 from Rauscher murine leukemia
      virus.
AB  - The envelope glycoproteins gp70 and gp45 were purified from Rauscher leukemia
      virus and compared in radioimmunoassay and gel diffusion using antibody to the
      purified proteins and a cross-reactive antibody prepared against feline leukemia
      virus. Previous studies indicated that gp70 and gp45 had very similar polypeptide
      components and differed mainly in carbohydrate content. The current studies
      indicate that gp70 contains the major antigenic determinants of gp45, and, in
      addition, determinants unique to gp70. We presume that these differences involve
      the carbohydrate components, either directly or indirectly by influence on
      conformation. The major antigenic deficiencies in gp45, relative to gp70,
      appeared to be in interspecies reactivity.

PMID- 18625485
TI  - Single-stranded DNA genome in a whitefly-transmitted plant virus.
AB  - Bean golden yellow mosaic virus (GYMV) DNA sedimented in sucrose density
      gradients and in an analytical ultracentrifuge as a single component. Values of
      s(20,w) which depended upon ionic strength (i) and pH, were 16.0 (pH = 7.0, i =
      0.1); 16.3 (pH = 7.0, i = 1.0); 9.0 (pH = 13, i = 0.1); and 12.0 (0.1 N NaOH, i =
      1.0). GYMV-DNA banded in CsCl as a single component with a buoyant density of
      1.7170 g/ml and exhibited hyperchromicity when heated between 20 and 70 degrees .
      Hyperchromicity and a shift in the ultraviolet light absorption maximum were
      observed when the DNA was treated with formaldehyde (1.8%) at room temperature.
      Nuclease sensitivity tests showed that the DNA was susceptible to hydrolysis by
      DNase I and nuclease S1 (specific for single-stranded DNA) but not to hydrolysis
      by RNase A or by 0.3 N NaOH. Molecular weight values calculated from
      sedimentation velocity and CsCl equilibrium data were in the range of 0.66 to
      0.95 x 10(6) daltons GYMV thus contains DNA with the properties of a
      predominantly single-stranded molecule and represents the first reported single
      stranded DNA virus from plants.

PMID- 18625486
TI  - The multisite character of host-range mutations in bacteriophage lambda.
AB  - Mapping of the h and hh * host-range mutations in phage lambda by two-point
      crosses with reference J- point mutations, and with lambdagal deleted for part of
      J, locates these mutations in the promoter-distal portion of the J cistron.
      Analysis of phenotypic h+ recombinants, formed in crosses of the type h or hh* x
      J-, or h+ revertants of h, hh* , and Jdef mutants, indicates that such phenotypic
      h+ particles often retain cryptic h determinants. Similar determinants are also
      present in some common laboratory strains of lambda. These h+ recombinants and
      revertants carry a variety of different h markers, since recombination analysis
      allows several classes of particles carrying cryptic h markers to be
      distinguished. These genetic data suggest that the extended host-range phenotype
      in lambda is due to multiple rather than single, mutations in the distal region
      of gene J, although the number of sites involved and their arrangement remain
      uncertain. The genetic location of the h and hh * mutations is confirmed at the
      physical level by comparing the tryptic peptide maps of the J proteins purified
      from lysates of cells infected with different h+, h, hh*, Jam, and J434 phage and
      from purified lambdah+ virions. Examination of these peptide maps shows there are
      several methionine-containing peptides altered in the h and hh * maps. Some of
      these altered peptides are derived from the C-terminal 5-10% of the J polypeptide
      in the region of nonhomology between lambda and 434.

PMID- 18625487
TI  - Surface features of vaccinia virus-infected human embryonic cells as studied by
      scanning electron microscopy.
AB  - Human embryonic cells were studied sequentially following infection with vaccinia
      virus by scanning electron microscopy (SEM). Normal human embryonic cells have a
      flattened polygonal and elongated shape and relatively smooth surfaces with few
      microvilli and flipodia. Vaccinia virus induced surface changes 0.5 hr after
      infection, which included the appearance of aggregates of microvilli and blebs.
      These changes were more striking after 2 hr, and the number of filipodia
      increased. Four hours after infection, most of the cells rounded up and
      polymorphic ruffles covered the entire surface of the cells. Cytosine arabinoside
      did not prevent the early surface alterations induced by the virus while addition
      of cycloheximide did. These results indicate that de novo protein synthesis but
      not DNA synthesis is required for the early morphologic changes induced by
      vaccinia virus. Further studies are required to understand the nature and
      underlying mechanisms of these surface alterations.

PMID- 18625488
TI  - Overproduction of a viral protein during infection of a lyc mutant of Escherichia
      coli with phage lambdamm434.
AB  - The bacterial lyc7 mutation probably affects the same gene as the hf1 mutation
      described by Belfort and Wulff and promotes increased lysogenisation by lambdoid
      phages. The synthesis of lambdoid phage-specific proteins has been examined after
      infection of ultraviolet light-irradiated lyc+ and lyc7 Escherichia coli strains,
      and a new protein with a molecular weight of 14,000 was observed to appear during
      infection of the mutant but not of the wild type. This protein may be the product
      of the phage cII gene.

PMID- 18625489
TI  - Properties of mouse leukemia viruses. XIV. Prevention of spontaneous AKR leukemia
      by treatment with group-specific antibody against the major virus gp71
      glycoprotein.
AB  - Treatment of AKR mice early in life with potent goat antibody to the major virus
      glycoprotein (gp71) of Friend leukemia virus resulted in marked prevention of
      fatal AKR disease. Even better protection could be achieved when, in addition,
      the mothers were treated with the same antibody at least 3-4 days antepartum.
      From these preliminary observations, we conclude that antibody specific for the
      broadly cross-reacting determinants of this virus glycoprotein can control
      development of spontaneous leukemias mediated by replicating endogenous viruses.

PMID- 18625490
TI  - Murine leukemia viruses containing an approximately 30 S RNA subunit of unknown
      biological activity, in addition to the 38 S subunit of the viral genome.
AB  - The 50-70 S RNA complex of a clone of Kirsten murine leukemia virus (Ki-MLV),
      propagated in NIH 3T3 cells, as well as that of a Moloney (Mo)-MLV, propagated in
      a mouse thymus-bone marrow cell line, contained an approximately 30 S RNA of
      unknown biological activity in addition to 38 S genomic RNA. The approximately 30
      S RNA shares with 38 S virion RNA the ability to form 50-70 S RNA complexes and
      to be packaged by virus particles. The morphology of the cell lines propagating
      these viruses was indistinguishable from that of uninfected controls.

PMID- 18625491
TI  - Membrane antigen expression in Epstein-Barr virus-infected Raji cells in the
      presence of phosphonoacetic acid.
AB  - The expression of the Epstein-Barr virus (EBV)-induced membrane antigen (MA) in
      Raji cells experimentally infected with EBV concentrates was inhibited by
      phosphonoacetic acid (PAA) as determined by membrane immunofluorescence and
      inhibition of antibody-dependent lymphocyte cytotoxicity. PAA was only effective
      if present during the first 24 hr following virus adsorption, indicating that the
      synthesis of MA was primarily a late viral gene function requiring viral DNA
      synthesis.

PMID- 18625492
TI  - Further studies on the association of herpes simplex virus type 1 DNA with host
      DNA during productive infection.
AB  - Our previous finding of an association between herpes simplex virus type 1 (HSV
      1) and African green monkey kidney (BSC-1) DNAs in productively infected cells
      has been extended by investigating the influence of the time course, temperature,
      and multiplicity of infection on the extent of this association. The interaction
      of host and viral DNAs was not only dependent on the concentration of
      intracellular viral DNA, but also upon the particular conditions of infection. An
      examination of the time course of infection revealed that the amount of free
      viral DNA per cell reached a maximum well before the amount of viral-host
      associated DNA did so, while an examination of the effect of temperature revealed
      a threefold variation in the amount of viral-host-associated DNA over a
      temperature range (33.5-39.5 degrees ) in which the amount of free viral DNA was
      essentially constant. The quantity of HSV-1 DNA associated with host-cell DNA
      ranges from about 100 to 1500 genome equivalents per cell, depending on the
      conditions of infection, and it appears that between 5 and 40% of the association
      is alkali stable.

PMID- 18625493
TI  - Differentiation of legume carlaviruses based on their biochemical properties.
AB  - Nucleic acids of alfalfa latent virus (ALV), pea streak virus (PSV), and red
      clover vein mosaic virus (RCVMV) were hydrolyzed by pancreatic RNase but not by
      DNase. ALV and PSV each had one single-stranded RNA of 38.0 and 37.6 S,
      respectively, whereas two single-stranded RNAs of 39.1 and 12-15 S were found in
      the RCVMV preparations. The average apparent molecular weights obtained by
      sedimentation and electrophoresis of formalinized ALV-RNA, PSV-RNA, and the large
      RNA of RCVMV were 2.45, 2.55, and 2.59 x 10(6), respectively. The apparent
      molecular weight of the protein subunit of ALV was 27,000, whereas those of PSV
      and RCVMV were each 33,500, indicating that ALV is a distinct member of the
      carlavirus group. RCVMV and PSV are considered distinct viruses, since
      formalinized RCVMV-RNA, but not PSV-RNA, was resolved from formalinized tobacco
      mosaic virus RNA on gradients and since the capsid protein subunit of RCVMV
      resisted degradation on storage but that of PSV did not.

PMID- 18625495
TI  - Disconnection's renaissance takes shape: Formal incorporation in group-level
      lesion studies.
AB  - Group-level voxelwise statistical analyses of lesion-deficit relationships have
      been used to implicate brain structures critical for specific aspects of human
      cognition and behavior. Current approaches fail to account for the role of fiber
      tract disruptions in causing deficit, and confound cortical damage with damage to
      fibers of passage. Here, we develop a framework, Generalized Lesion-Symptom
      Mapping (GLSM), to integrate fiber tract information from DTI-based tractographic
      atlases in tractwise and voxelwise lesion-deficit analyses. First, we used the
      geniculo-calcarine system as a validation testbed. Using logistic regressions we
      predicted right homonymous visual field deficits in 149 subjects with focal brain
      damage based on lesion location, with and without incorporating fiber tract
      information. A probabilistic fiber tract atlas [Wakana S, Jiang H, Nagae
      Poetscher LM, Van Zijl PC, Mori S. Fiber tract-based atlas of human white matter
      anatomy. Radiology 2004;230:77-87] coregistered to our reference brain was used
      to estimate disconnection to the optic radiations and adjacent fiber tracts. When
      tract information was not incorporated, lesions in multiple sectors of the
      temporal lobe were associated with visual field defects. When the optic
      radiations were incorporated, this artifactual association was eliminated and the
      calcarine cortex was correctly isolated. Among the incorporated tracts, only the
      optic radiations significantly predicted visual field defects. Second, we applied
      the approach to impairments of higher visuoperceptual functions in 111 subjects
      who were administered the Hooper Visual Organization Test. We included all six
      association fiber tracts available in the atlas, plus the optic radiations. Tract
      inclusion narrowed the cortical sectors associated with impaired performance in a
      manner consistent with recent fMRI findings. The left cingulum and inferior
      longitudinal fasciculus, significantly predicted impairments. The results
      demonstrate the viability, validity and value of incorporating fiber tract
      information in lesion-deficit analyses. The enhanced analysis framework opens a
      new avenue for studying neural systems, with the potential to facilitate
      identification of both cortical sectors and fiber tracts critical for cognitive
      functioning.

PMID- 18625494
TI  - Phonological dyslexia and dysgraphia: cognitive mechanisms and neural substrates.
AB  - To examine the validity of different theoretical assumptions about the
      neuropsychological mechanisms and lesion correlates of phonological dyslexia and
      dysgraphia, we studied written and spoken language performance in a large cohort
      of patients with focal damage to perisylvian cortical regions implicated in
      phonological processing. Despite considerable variation in accuracy for both
      words and non-words, the majority of participants demonstrated the increased
      lexicality effects in reading and spelling that are considered the hallmark
      features of phonological dyslexia and dysgraphia. Increased lexicality effects
      were also documented in spoken language tasks such as oral repetition, and
      patients performed poorly on a battery of phonological tests that did not involve
      an orthographic component. Furthermore, a composite measure of general
      phonological ability was strongly predictive of both reading and spelling
      accuracy, and we obtained evidence that the continuum of severity that
      characterized the written language disorder of our patients was attributable to
      an underlying continuum of phonological impairment. Although patients
      demonstrated qualitatively similar deficits across measures of written and spoken
      language processing, there were quantitative differences in levels of performance
      reflecting task difficulty effects. Spelling was more severely affected than
      reading by the reduction in phonological capacity and this differential
      vulnerability accounted for occasional disparities between patterns of impairment
      on the two written language tasks. Our findings suggest that phonological
      dyslexia and dysgraphia in patients with perisylvian lesions are manifestations
      of a central or modality-independent phonological deficit rather than the result
      of damage to cognitive components dedicated to reading or spelling. Our results
      also provide empirical support for shared-components models of written language
      processing, according to which the same central cognitive systems support both
      reading and spelling. Lesion-deficit correlations indicated that phonological
      dyslexia and dysgraphia may be produced by damage to a variety of perisylvian
      cortical regions, consistent with distributed network models of phonological
      processing.

PMID- 18625496
TI  - Scepticism is not enough.

PMID- 18625497
TI  - Event-related potential correlates of paranormal ideation and unusual
      experiences.
AB  - Separate dimensions of schizotypy have been differentially associated with
      electrophysiological measures of brain function, and further shown to be modified
      by sex/gender. We investigated event-related potential (ERP) correlates of two
      subdimensions of positive schizotypy, paranormal ideation (PI) and unusual
      experiences (UEs). Seventy-two individuals with no psychiatric diagnosis (men=36)
      completed self-report measures of UE and PI and performed an auditory oddball
      task. Average scores for N100, N200 and P300 amplitudes were calculated for left
      and right anterior, central and posterior electrode sites. Multiple linear
      regression was used to examine the relationships between the measures of
      schizotypy and ERPs across the entire sample, as well as separately according to
      sex. PI was inversely associated with P300 amplitude at left-central sites across
      the entire sample, and at right-anterior electrodes in women only. Right-anterior
      P300 and right-posterior N100 amplitudes were negatively associated with UE in
      women only. Across the entire sample, UE was negatively associated with left
      central N100 amplitude, and positively associated with left-anterior N200
      amplitude. These results provide support from electrophysiological measures for
      the fractionation of the positive dimension of schizotypy into subdimensions of
      PI and UE, and lend indirect support to dimensional or quasidimensional
      conceptions of psychosis. More specifically, they suggest that PI may be
      associated with alteration in contextual updating processes, and that UE may
      reflect altered sensory/early-attention (N100) mechanisms. The sex differences
      observed are consistent with those previously observed in individuals with
      schizophrenia.

PMID- 18625498
TI  - A re-assessment of erythropoietin as a neuroprotective agent following rat spinal
      cord compression or contusion injury.
AB  - This study was initiated due to an NIH "Facilities of Research--Spinal Cord
      Injury" contract to support independent replication of published studies that
      appear promising for eventual clinical testing. We repeated a study reporting the
      beneficial effects of recombinant human erythropoietin (rhEPO) treatment after
      spinal cord injury (SCI). Moderate thoracic SCI was produced by two methods: 1)
      compression due to placement of a modified aneurysm clip (20 g, 10 s) at the T3
      spinal segment (n=45) [followed by administration of rhEPO 1000 IU/kg/IP in 1 or
      3 doses (treatment groups)] and 2) contusion by means of the MASCIS impactor (n =
      42) at spinal T9 (height 12.5 cm, weight 10 g) [followed by the administration of
      rhEPO 5000 IU/kg/IP for 7d or single dose (treatment groups)]. The use of rhEPO
      following moderate compressive or contusive injury of the thoracic spinal cord
      did not improve the locomotor behavior (BBB rating scale). Also, secondary
      changes (i.e. necrotic changes followed by cavitation) were not significantly
      improved with rhEPO therapy. With these results, although we cannot conclude that
      there will be no beneficial effect in different SCI models, we caution
      researchers that the use of rhEPO requires further investigation before
      implementing clinical trials.

PMID- 18625500
TI  - Age-related differences in NFkappaB translocation and Bcl-2/Bax ratio caused by
      TNFalpha and Abeta42 promote survival in middle-age neurons and death in old
      neurons.
AB  - Alzheimer's disease is associated with an age-related accumulation of Abeta and
      inflammation. The inflammatory mediator, TNFalpha activates a signaling cascade
      involving NFkappaB translocation to the nucleus and a beneficial or detrimental
      transcriptional response, depending on the age of the neurons and the type of
      stress applied. Relative to treatment with Abeta42 alone, previously we found
      that TNFalpha plus Abeta42, applied to old rat neurons (24 month) is toxic, while
      the same treatment of middle-age neurons (10 month) is protective. In contrast to
      improved survival of middle-age rat cortical neurons, neurons from old rats are
      killed by TNFalpha plus Abeta42 despite greater p50 nuclear translocation. In
      middle-age neurons, blocking TNFR1 does not affect NFkappaB translocation,
      whereas blocking TNFR2 results in an increase in NFkappaB translocation. For old
      neurons, blocking either receptor, does not change NFkappaB translocation, but
      improves cell survival. To account for these effects on cell viability in
      response to TNF+Abeta, measures of the Bcl-2/Bax ratio positively correlate with
      survival. In the setting of old neurons, these results suggest that overactivated
      nuclear translocation of NFkappaB and lower Bcl-2 levels promote death that is
      reduced by inhibition of either TNFR1 or R2.

PMID- 18625501
TI  - Sarcocystis neurona: molecular characterization of enolase domain I region and a
      comparison to other protozoa.
AB  - Sarcocystis neurona causes protozoal myeloencephalitis and has the ability to
      infect a wide host range in contrast to other Sarcocystis species. In the current
      study, five S. neurona isolates from a variety of sources, three Sarcocystis
      falcatula, one Sarcocystis dasypi/S. neurona-like isolate, and one Besnoitia
      darlingi isolate were used to compare the enolase 2 gene segment containing the
      domain I region to previously sequenced enolase genes from Neospora caninum,
      Neospora hughesi, Toxoplasma gondii, Plasmodium falciparum, and Trypanosoma
      cruzi; enolase 2 segment containing domain I region is highly conserved amongst
      these parasites of veterinary and medical importance. Immunohistochemistry
      results indicates reactivity of T. gondii enolase 1 and 2 antibodies to S.
      neurona merozoites and metrocytes, but no reactivity of anti-enolase 1 to the S.
      neurona bradyzoite stage despite reactivity to T. gondii bradyzoites, suggesting
      expression differences between organisms.

PMID- 18625502
TI  - An unusual presentation of uterus didelphys with obstructed hemivagina with
      ipsilateral renal agenesis.
AB  - OBJECTIVE: To report a rare mullerian anomaly of uterus didelphys with obstructed
      hemivagina and renal agenesis, and its unusual presentation that mimicked an
      ischiorectal swelling. DESIGN: Case report. SETTING: Private clinic and surgical
      center. PATIENT(S): A 17-year-old woman referred for evaluation of a suspected
      mullerian anomaly. INTERVENTION(S): Clinical, hysteroscopic, and laparoscopic
      evaluation of the anomaly, with treatment and follow-up assessments. MAIN OUTCOME
      MEASURE(S): Assessment of the anomaly according to the standard mullerian
      classification system with a subsequent literature search. RESULT(S): Successful
      drainage of hematocolpos and hematometra, and subsequent normal menstruation.
      CONCLUSION(S): This rare mullerian anomaly, also known as Herlyn-Werner
      Wunderlich syndrome (HWWS), presented as a huge paravaginal mass. Good long-term
      outcome occurred after vaginal septectomy. This diagnosis should be suspected in
      women who have a pelvic mass and ipsilateral renal agenesis.

PMID- 18625499
TI  - Neuroinflammation as a neurotoxic mechanism in alcoholism: commentary on
      "Increased MCP-1 and microglia in various regions of human alcoholic brain".

PMID- 18625503
TI  - Working to improve implantation.

PMID- 18625505
TI  - The complexities of receptor binding.

PMID- 18625507
TI  - More to be learned about female and male genital tract malformations.

PMID- 18625508
TI  - Identification of nucleoli in the early branching protist Giardia duodenalis.
AB  - Giardia duodenalis has been described as 'anucleolated'. In this work we analysed
      the subcellular distribution of several nucleolar markers in Giardia nuclei using
      silver and immunostaining techniques for electron and confocal laser microscopy
      as well as expression of epitope-tagged proteins in transgenic trophozoites. We
      identified anteronuclear fibrogranular structures corresponding to nucleolar
      organising regions with recruited ribonucleoprotein complexes, rRNA and epitope
      tagged fibrillarin and rRNA-pseudouridine synthase (CBF5). Recombinant
      fibrillarin and CBF5 were targeted to this subcompartment. This study
      demonstrates the presence of nucleoli in G. duodenalis and provides a model to
      analyse minimal requirements for nucleolar assembly and maintenance in eukaryotic
      cells.

PMID- 18625509
TI  - A novel bioassay for B-cell activating factor (BAFF) based on expression of a
      BAFF-receptor ectodomain-tumour necrosis factor-related apoptosis-inducing ligand
      (TRAIL) receptor-2 endodomain fusion receptor in human rhabdomyosarcoma cells.
AB  - B-cell activating factor (BAFF) is a type II transmembrane glycoprotein belonging
      to the tumour necrosis factor ligand superfamily. Active soluble forms of BAFF
      are generated either by cleavage of the extracellular domain or by recombinant
      DNA technology. The current bioassay for measuring the activity of soluble BAFF
      involves stimulation of the proliferation of mouse splenic B-cells in the
      presence of goat anti-mouse IgMmicro chain which is rather cumbersome and lengthy
      and yields variable results. We have therefore developed an alternative
      functional assay which relies on the ability of BAFF to induce an apoptotic
      response in human rhabdomyosarcoma cells. For this, we constructed a chimeric
      receptor containing the ectodomain of the MuBAFF-R--the major cell receptor for
      BAFF--and the endodomain of the HuTRAIL-R2--one of the two functional receptors
      for TRAIL--which is known to contain a death domain and trigger apoptosis. When
      the chimeric receptor was expressed in the TRAIL-sensitive human rhabdomyosarcoma
      cell line KD4 clone 21, recombinant BAFF of either human or mouse sequence
      stimulated apoptosis, similar to TRAIL, in a dose-dependent manner. The
      transfected cell population, called FL17, expressing the MuBAFF-R/ HuTRAIL-R2
      thus provided the basis of a novel functional bioassay for BAFF that is simple
      and relatively fast to perform. The construction of the chimeric receptor,
      development of the transfected cells expressing this receptor and the development
      of sensitive and reproducible bioassays for BAFF and anti-BAFF neutralising
      antibodies are described.

PMID- 18625510
TI  - Alpha-conopeptides specifically expressed in the salivary gland of Conus
      pulicarius.
AB  - To date, studies conducted on cone snail venoms have attributed the origins of
      this complex mixture of neuroactive peptides entirely to gene expression by the
      secretory cells lining the lumen of the venom duct. However, specialized tissues
      such as the salivary glands also secrete their contents into the anterior gut and
      could potentially contribute some venom components injected into target animals;
      evidence supporting this possibility is reported here. Sequence analysis of a
      cDNA library created from a salivary gland of Conus pulicarius revealed the
      expression of two transcripts whose predicted gene products, after post
      translational processing, strikingly resemble mature conopeptides belonging to
      the alpha-conotoxin family. These two transcripts, like alpha-conotoxin
      transcripts, putatively encode mature peptides containing the conserved A
      superfamily cysteine pattern (CC-C-C) but the highly conserved A-superfamily
      signal sequences were not present. Analysis of A-superfamily members expressed in
      the venom duct of the same C. pulicarius specimens revealed three putative alpha
      conotoxin sequences; the salivary gland transcripts were not found in the venom
      duct cDNA library, suggesting that these alpha-conotoxins are salivary gland
      specific. Therefore, expression of conotoxin-like gene products by the salivary
      gland could potentially add to the complexity of Conus venoms.

PMID- 18625511
TI  - Polycyclic aromatic hydrocarbon transport processes on the scale of a flood event
      in the rural watershed of Le Bebec, France.
AB  - Transport processes of polycyclic aromatic hydrocarbons (PAHs) were investigated
      in a rural watershed in France, which led to new quantitative results on the
      scale of a flood event. For that purpose, principal components analysis (PCA)
      combined with signal decomposition of PAH Breakthrough curves were used. The
      results obtained by PCA enabled us to distinguish (i) the transport of low
      molecular weight PAHs in dissolved form and (ii) the transport of high molecular
      weight PAHs in particulate form. The intermediate molecular weight PAHs are
      distributed in these two clusters. The application of a signal decomposition
      method confirms the results of PCA and makes it possible to quantify the mass PAH
      resulting, respectively, from resuspension (13.3mg, i.e. 77% of the total mass)
      and from direct transfer (2.8mg=16% of the total mass). For the resuspension
      phase, desorption of PAH (38% of the total exported mass) could be also
      distinguished from sediment resuspension (39%).

PMID- 18625512
TI  - The treatment of waste air containing phenol vapors in biotrickling filter.
AB  - This research aimed at investigating the biodegradation of phenol contaminated
      air streams in biotrickling filter. The effect of inlet concentration (200-1000
      ppmv) and empty bed contact time (EBCT) (15-60 s) were investigated under steady
      state, transient and shock loading, and shutdown periods. Upon rapid start up
      operation, inlet phenol concentrations of up to 1000 ppmv did not significantly
      affect the performance of the biotrickling filter at EBCT of 60 s, so that
      removal efficiency was well greater than 99%. In addition, the EBCT as low as 30
      s did not have detrimental effects on the efficiency of the bioreactor and phenol
      removal was greater than 99%. Decreasing the EBCT to 15s reduced the removal
      efficiency to around 92%. The maximum elimination capacity obtained in the
      biotrickling filter was 642 g(phenol) m(-3) h(-1), where the removal efficiency
      was only 57%. Results from the transient loading experiments revealed that the
      biotrickling filter could effectively handle the variations of the inlet loads
      without the phenol removal capacity being significantly affected.

PMID- 18625513
TI  - Transfer of metals to plants and red deer in an old lead mining area in Spain.
AB  - Lead mining in the Sierra Madrona mountains and the valley of Alcudia in Southern
      Spain began in the 1st millennium B.C., and the area was intermittently exploited
      up until the end of the 20th century. The degree of contamination by Pb, Zn, Cd,
      Cu, As and Se of soil, water and sediment, and the transfer to 13 species of
      plants, and then to red deer (Cervus elaphus) have been studied. Mined areas had
      higher concentrations in stream sediments than control areas. The highest
      concentrations were observed for Pb (1481 microg g(-1) d.w.) and As (1880 microg
      g(-1)) in the sediment of a stream flowing beside the spoil dump at Mina de
      Horcajo. Plants from mining sites contained consistently higher levels of Pb and
      As, and their concentrations in plants were correlated. The highest
      concentrations of Pb were in Gramineae (Pb: 97.5, As: 2.4 microg g(-1) d.w.), and
      the lowest in elmleaf blackberry (Rubus ulmifolius). The highest mean liver
      concentrations were found in red deer from the mining sites for Pb (0.805 microg
      g(-1) d. w.), Cd (0.554 microg g(-1)), Se (0.327 microg g(-1)), and As (0.061
      microg g(-1)), although these were well below the levels associated with clinical
      poisoning.

PMID- 18625514
TI  - A land-use regression model for estimating microenvironmental diesel exposure
      given multiple addresses from birth through childhood.
AB  - The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is a
      prospective birth cohort whose purpose is to determine if exposure to high levels
      of diesel exhaust particles (DEP) during early childhood increases the risk for
      developing allergic diseases. In order to estimate exposure to DEP, a land-use
      regression (LUR) model was developed using geographic data as independent
      variables and sampled levels of a marker of DEP as the dependent variable. A
      continuous wind direction variable was also created. The LUR model predicted 74%
      of the variability in sampled values with four variables: wind direction, length
      of bus routes within 300 m of the sample site, a measure of truck intensity
      within 300 m of the sampling site, and elevation. The LUR model was subsequently
      applied to all locations where the child had spent more than eight hours per week
      from through age three. A time-weighted average (TWA) microenvironmental exposure
      estimate was derived for four time periods: 0-6 months, 7-12 months, 13-24
      months, 25-36 months. By age two, one third of the children were spending
      significant time at locations other than home and by 36 months, 39% of the
      children had changed their residential addresses. The mean cumulative DEP
      exposure estimate increased from age 6 to 36 months from 70 to 414 microg/m3
      days. Findings indicate that using birth addresses to estimate a child's exposure
      may result in exposure misclassification for some children who spend a
      significant amount of time at a location with high exposure to DEP.

PMID- 18625515
TI  - Endocrine alteration and other biochemical responses in juvenile turbot exposed
      to the Prestige fuel oil.
AB  - Juvenile turbot (Scophthalmus maximus) were exposed to different concentrations
      of the Prestige fuel oil through the diet. The effects on hepatic
      biotransformation enzymes, namely, 7-ethoxyresorufin O-deethylase (EROD),
      catalase, and phase II activities - UDP-glucuronosyltransferases (UGT) and
      cytosolic sulfotransferases (SULT) -, were monitored after 42-day exposure.
      Additionally, potential alterations on the endocrine system of juvenile turbot
      were assessed by measuring circulating levels of testosterone and 17beta
      estradiol in plasma, together with gonadal P450 aromatase activity and the
      glucuronidation of testosterone by liver microsomal fractions. Fluorescent
      aromatic compounds (FACs) in bile were determined as an indicator of exposure to
      polycyclic aromatic hydrocarbons (PAHs). EROD activity increased in a dose
      dependent manner, and a positive correlation between levels of FACs in bile and
      EROD activity was observed. A significant increase in UGT activity was observed
      in fish exposed to medium and high fuel doses, whereas SULT cytosolic activity
      was not responsive to exposure. Exposure to the Prestige fuel oil sharply reduced
      circulating levels of testosterone in plasma. The obtained results suggest the
      ability of the Prestige fuel oil to alter hepatic biotransformation enzymes and
      to disrupt endogenous hormone levels in juvenile turbot, with unknown
      consequences in terms of sexual differentiation and reproduction.

PMID- 18625516
TI  - Maximizing pollutant removal in constructed wetlands: should we pay more
      attention to macrophyte species selection?
AB  - While the positive role of macrophytes on removal efficiency in constructed
      wetlands has been well established, possible differences in performance between
      plants species of comparable life forms and sizes are much harder to demonstrate.
      We reviewed 35 experimental studies published in peer-reviewed journals and
      proceedings on the effect of macrophyte species selection on pollutant removal in
      SSFCW. The studies cover a wide range of macrophyte species, experimental
      approaches (from well-replicated microcosm experiments to comparison between full
      full-size constructed wetlands), climatic conditions (from tropical to cold
      temperate) and types of effluent (domestic, industrial, etc.). Frequent
      methodological limitations in these studies compel caution in the interpretation
      of their results. Yet, the fact that the majority found some (occasionally large)
      differences in efficiency between plant species for one or more type of pollutant
      suggests that macrophyte species selection does matter. However, there is little
      generalization to be made that could help guide species selection for SSFCW,
      except for the exact conditions in which the experiments were done. For example,
      the same pair of species that was tested in different studies occasionally gave
      opposite results in terms of which one performs best. Also, most studies provided
      few insights on the mechanisms or plant properties that could explain the
      observed differences in plant species efficiency. Finally, we discuss other
      relevant research questions and approaches that could help better guide
      macrophyte species selection for CW.

PMID- 18625517
TI  - Salvianolic acid B inhibits platelet adhesion under conditions of flow by a
      mechanism involving the collagen receptor alpha2beta1.
AB  - Salvianolic acid B (SAB) is a component of Danshen, a herb widely used in Chinese
      medicine, and was previously shown to exert a number of biological activities
      including inhibition of platelet function, but the exact mechanisms involved are
      unclear. SAB dose-dependently inhibited platelet deposition from flowing,
      anticoagulated whole blood to immobilized collagen at both venous and arterial
      shear rate, whereas platelet deposition to immobilized fibrinogen was not
      affected. The inhibitory effect of SAB on platelet adhesion to collagen was
      independent of alphaIIbbeta3, since SAB still inhibited platelet deposition in
      the presence of a alphaIIbbeta3-blocking peptide. SAB inhibited static platelet
      adhesion to a synthetic peptide specific for the collagen receptor alpha2beta1,
      whereas platelet adhesion to a glycoprotein VI-specific peptide was not affected.
      SAB inhibited binding of an antibody against alpha2beta1 to platelets as studied
      by flow cytometry, and inhibited the interaction of soluble alpha2beta1 to
      immobilized collagen in a solid phase binding assay. These combined results
      indicate that SAB inhibits platelet adhesion to immobilized collagen by
      interfering with the collagen receptor alpha2beta1.

PMID- 18625518
TI  - Cervical and hysteroscopic injection for identification of sentinel lymph node in
      endometrial cancer.
AB  - OBJECTIVES: The aims of our study were to evaluate the possibility of identifying
      the sentinel lymph node (SLN) in patients with endometrial cancer (EC) and to
      directly compare two injection techniques, cervical and hysteroscopic injection.
      METHODS: Fifty-four patients with endometrial carcinoma, clinical stages I and
      II, were submitted to complete surgical staging through laparoscopy, as
      recommended by FIGO in 1988. For the mapping procedure the patients were divided
      into two groups of injection: the cervical injection group and hysteroscopic
      injection group. Technetium (Tc) 99m radiocolloid was used as tracer. RESULTS:
      Intraoperative detection rate of SLN was 70% in cervical group and 65% in the
      hysteroscopic group (p=n.s.). In the cervical group, all patients had SLN in the
      pelvis only and the mean SLN removed was 18 (range 2-26). In the hysteroscopic
      group, all patients had SNLs in the pelvis and two patients had SLN both in the
      pelvis and above the bifurcation of the aorta. Mean pelvic SLN removed was 20
      (range 8-42). CONCLUSIONS: Our data shows that it is possible to identify the SLN
      in tumours of the endometrium. Both cervical and hysteroscopic techniques are
      feasible but the hysteroscopic procedure might represent the only method able to
      highlight the complete lymphatic drainage of the uterus as suggested by the
      presence of paraaortic positive SLN only in this group.

PMID- 18625519
TI  - Gender issues in suicide rates, trends and methods among youths aged 15-24 in 15
      European countries.
AB  - BACKGROUND: No recent cross-country examinations for youth suicide trends and
      methods for Europe were found. AIM: The aim of the study is to specify
      differences in suicide rates, trends and methods used among 15-24 years olds by
      gender across 15 European countries. METHOD: Data for 14,738 suicide cases in the
      age group 15-24 in 2000-2004/5 were obtained and analysed. RESULTS: Suicide rates
      ranged 5.5-35.1 for males and 1.3-8.5 for females. Statistically significant
      decline since 2000 was observed in Germany, Scotland, Spain, and England for
      males and in Ireland for females. Hanging was most frequently used for both
      genders, followed by jumping and use of a moving object for males and jumping and
      poisoning by drugs for females. Male suicides had a higher risk than females of
      using firearms and hanging and lower risk of poisoning by drugs and jumping.
      There were large differences between single countries. LIMITATIONS: The
      limitations of the study are the small numbers of specific suicide methods in
      some countries as well as the re-categorisation of ICD-9 codes into ICD-10 in
      England, Ireland and Portugal. Further, the use of suicides (X60-X84) without
      events of undetermined deaths (Y10-Y34) continues to be problematic considering
      the possibility of "hidden suicides". CONCLUSIONS: The present study shows that
      suicide rates among young males are decreasing since 2000 in several European
      countries. Analysis of suicide methods confirms that there is a very high
      proportion of hanging in youths, which is extremely difficult to restrict.
      However, besides hanging there are also high rates of preventable suicide methods
      and reducing the availability of means should be one of the goals of suicide
      prevention.

PMID- 18625520
TI  - Pre-migration planning and depression among new migrants to Hong Kong: the
      moderating role of social support.
AB  - BACKGROUND: Although it is a well-known fact that migration is a risk factor
      contributing to psychopathology, little is known about how pre-migration factors
      may lead to depression among migrants. The present study examined the
      relationship between poorly planned migration and depressive symptoms, and
      evaluated the moderating roles of optimism, sense of control, and social support
      in the relationship between pre-migration planning and depression among new
      immigrants from Mainland China to Hong Kong. METHODS: A representative sample of
      449 migrants aged 18 and above were interviewed in 2007 using a face-to-face
      format. The 20-item Center for Epidemiological Studies of Depression (CES-D)
      scale was used to measure depressive symptoms, and a series of questions
      regarding socio-demographic characteristics (age, gender, marital status,
      education, and household income), optimism, sense of control, and social support
      were also included. RESULTS: A total of 26.5% of our sample scored 16 or above on
      the CES-D scale, which indicated a clinically significant case of depression.
      Poor migration planning was significantly related to CES-D scores after adjusting
      for all socio-demographic variables and three psycho-social factors. In addition,
      optimism, sense of control, and social support were also significantly related to
      the CES-D score. It was also found that social support reduced the harmful impact
      of poor migration planning on depressive symptoms. CONCLUSIONS: New immigrants to
      Hong Kong from Mainland China are at risk for depressive symptoms, especially
      those who are not well prepared for migration; therefore, prevention measures,
      particularly strengthening their social support in Hong Kong, should be
      considered seriously by policy makers.

PMID- 18625521
TI  - Predictors of relapse in a study of duloxetine treatment in patients with major
      depressive disorder.
AB  - BACKGROUND: Using data from a relapse prevention study of duloxetine treatment
      for adults with major depressive disorder (MDD), we examined demographic- and
      illness-related variables to identify factors that may predict relapse of MDD.
      METHODS: Post-hoc analyses, using the Cox proportional hazards model, were
      performed on data from a study designed to compare the time to relapse of MDD in
      duloxetine- and placebo-treated patients. Patients received open-label duloxetine
      60 mg/day during a 12-week acute phase, and those who met response criteria were
      randomly assigned to duloxetine 60 mg/day (N=136) or placebo (N=142) during a 26
      week double-blind continuation phase. RESULTS: Significant predictors of relapse
      were VAS back pain score at entry >30, HAMD(17) total score at randomization >7,
      and geography (Europe vs. US). Four significant treatment-by-predictor
      interactions were identified: the SQ-SS pain subscale score at entry>median of 4,
      VAS overall pain score at entry >30, VAS overall pain score at entry>median of
      26, and VAS overall pain score at randomization>median of 7. In the "greater
      severity" category, the risk of relapse was significantly lower for duloxetine
      treated patients compared with placebo-treated patients. LIMITATIONS: These were
      post-hoc analyses. CONCLUSIONS: Higher levels of pain severity and depressive
      symptoms and a US geographical location were significant predictors of relapse in
      patients with MDD.

PMID- 18625522
TI  - BAFF is up-regulated in central nervous system of neuro-Behcet's disease.
AB  - We report that B cell-activating factor of the tumor necrosis factor family
      (BAFF) is expressed in central nervous system (CNS) of neuro-Behcet's disease
      (NBD). This study investigated BAFF and BAFF-R (BAFF receptor) in NBD, compared
      to multiple sclerosis (MS) and to non inflammatory neurological diseases (NIND).
      Cerebrospinal fluid (CSF) was used to determine the level of BAFF messenger RNA
      (mRNA) and the level of BAFF-R mRNA in unfractionated cells. A sandwich ELISA was
      used to quantify soluble BAFF protein levels in serum and in CSF. BAFF and BAFF-R
      expression in CSF were increased in NBD and MS patients compared to NIND
      patients. RNA levels of BAFF and BAFF-R were significantly correlated in NBD and
      MS patients. Serum sBAFF levels were increased in NBD and MS patients, but did
      not correlate with BAFF expression in CSF. CNS-produced BAFF may support
      inflammatory cell survival in NBD.

PMID- 18625523
TI  - Right ventricular contractile reserve in mitral stenosis: implications on
      hemodynamic burden and clinical outcome.
AB  - BACKGROUND: We investigated whether isovolumic acceleration (IVA) under inotropic
      stimulation as a means of right ventricular (RV) contractile reserve, is a
      surrogate for hemodynamic burden and has prognostic value in patients with mitral
      stenosis (MS). METHODS: Thirty-one pure MS patients and 20 controls underwent
      cardiac catheterization, exercise test, and dobutamine stress echocardiography.
      RV fractional area change (FAC), +dP/dt/P(max), RV tissue Doppler indices
      (isovolumic contraction [IVC] and systolic [S] velocity, and IVA) were measured.
      Patients were followed-up for the occurrence of cardiac adverse events. RESULTS:
      Inotropic modulation unmasked statistically significant differences regarding
      magnitude of changes in IVA, IVC, S, and +dP/dt/P(max), but not RV FAC. Inability
      to increase IVA more than 6.5 m/s(2) was the only independent determinant of
      pulmonary capillary wedge pressure >or=18 mm Hg (P=.004). Although MS severity
      did not predict the RV contractile reserve and pulmonary artery pressure (PAP)
      behavior during inotropic stimulation, the RV contractile reserve was related to
      the degree of systolic PAP. IVA increases of <3.4 m/s(2) had 86% sensitivity and
      75% specificity to predict unfavorable outcomes during long-term follow-up (20+/
      8 months). CONCLUSION: RV contractile reserve provides complementary data to the
      hemodynamic significance of MS severity, may contribute to clinical decision
      making, and be of prognostic value in these patients.

PMID- 18625524
TI  - Premature coronary artery disease in young (age <45) subjects: interactions of
      lipid profile, thrombophilic and haemostatic markers.
AB  - BACKGROUND: Intravascular thrombogenesis is influenced by a complex interplay of
      procoagulant, anticoagulant, fibrinolytic, endothelial damage/dysfunction and
      inflammatory factors. We hypothesised that abnormalities of these biological
      systems would contribute to coronary artery disease presenting at a young age.
      METHODS: We performed a case-control study of 142 subjects presenting with MI at
      a young age (<or=45 years; 'cases'), who were compared with 95 controls. We
      assessed for abnormalities of thrombophilia [total homocysteine (tHcy),
      lipoprotein (a) [Lp(a)], antiphospholipid antibodies (APA)], lipid profile [total
      cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides], fibrinogen and
      fibrin D-dimer (an index of thrombogenesis), endothelial damage/dysfunction (von
      Willebrand factor [vWF]), fibrinolysis (tissue plasminogen activator [t-PA
      antigen] and its inhibitor [PAI-1 antigen]) and inflammation (C-reactive protein
      [CRP]). RESULTS: Cases had significantly higher Lp(a) (p=0.008), triglycerides
      (p=0.001), fibrinogen (p=0.006), fibrin D-dimer (p=0.006) and vWf (p=0.032), but
      lower HDL-C (p=0.003) levels. There were no significant differences in tHcy, APA
      titre, total cholesterol or LDL-C, t-PA, PAI-1 and CRP levels (all p=NS). In a
      multivariate analysis, the only variables independently associated with cases
      were levels of Lp(a) (p=0.015), fibrinogen (p=0.038) and D-dimer (p=0.005)
      levels. CONCLUSIONS: Premature coronary artery disease is characterized by an
      unfavourable lipid profile, low concentrations of HDL-C and high triglyceride
      levels, in association with high Lp(a) and a hypercoagulable state (high
      fibrinogen and D-dimer levels).

PMID- 18625525
TI  - Cardiovascular manifestations associated with influenza virus infection.
AB  - Influenza accounts for 3 to 5 million cases of severe illness and up to 300,000
      deaths annually. Cardiovascular involvement in acute influenza infection can
      occur through direct effects of the virus on the myocardium or through
      exacerbation of existing cardiovascular disease. Epidemiological studies have
      demonstrated an association between influenza epidemics and cardiovascular
      mortality and a decrease in cardiovascular mortality in high risk patients has
      been demonstrated following vaccination with influenza vaccine. Influenza is a
      recognised cause of myocarditis which can lead to significant impairment of
      cardiac function and mortality. With recent concerns regarding another potential
      global pandemic of influenza the huge potential for cardiovascular morbidity and
      mortality is discussed.

PMID- 18625526
TI  - Risk of cardiovascular and cerebrovascular events after atrial fibrillation
      diagnosis.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with subsequent cardiovascular
      events including ischemic stroke, transient ischemic events, and coronary events.
      This study aimed to evaluate the risk of ischemic cerebrovascular events (ICVE),
      coronary events (CE) or heart failure (HF) following a diagnosis of AF. METHODS:
      Patients were selected from the UK General Practice Research Database. The
      incidence of ICVE, CE and HF was determined during a 6-year follow-up period for
      patients with a first diagnosis of AF (n=831) and a control group without AF
      (n=8226). Relative risk of developing a cardiovascular event associated with
      prior AF and other potential risk factors was estimated using Cox regression
      analysis. RESULTS: A first diagnosis of ICVE, CE or HF was made in 261 patients
      in the AF group and 622 in the control group. The relative risks associated with
      AF were 2.1 for CE (95% CI: 1.6-2.9), 3.0 for ICVE (95% CI: 2.3-4.0) and 6.4 for
      HF (95% CI: 5.0-8.3). The risks of CE, HF and ICVE were higher in patients with
      chronic AF than paroxysmal AF (odds ratio: 1.5, 95% CI: 1.0-2.2) and in patients
      aged at least 60 years or with diabetes. Lifestyle factors did not significantly
      affect the risk of cardiovascular events in patients with AF. CONCLUSIONS: After
      a first episode of AF there is an increased risk of ICVE, CE and HF. Patients
      initially diagnosed with chronic AF have a higher risk than those with paroxysmal
      AF.

PMID- 18625527
TI  - Stent implantation in patients with severe left ventricular systolic dysfunction.
AB  - BACKGROUND: Patients with ischemic severe left ventricular (LV) dysfunction are
      at higher risk for death. We assessed the outcome following percutaneous coronary
      intervention (PCI) in patients with LV systolic dysfunction. METHODS: From April
      1993 to March 2004 337 consecutive patients with LV ejection fraction
      (LVEF)<or=35% underwent elective stent implantation at out Institutions. RESULTS:
      The in-hospital course was uneventful in 322 (95.3%) patients. In-hospital death
      occurred in 5 patients (1.5%). At 2-year, 83 patients (24.6%) died (Non-surviving
      group), whereas 254 (75.4%) were alive (Surviving group). Sudden death occurred
      in 65% of cases. An acute myocardial infarction at follow-up occurred more often
      in the Non-surviving group (18% versus 5.4%; p=0.001). An implantable
      cardioverter-defibrillator (ICD) was implanted in 6.7% of patients in the Non
      surviving group versus 20.7% of the Surviving group (p=0.005). LVEF significantly
      improved at follow-up only in the Surviving group (29+/-6 to 35+/-11; p<0.001),
      whereas remained unchanged in the Non-surviving group (27+/-5 to 26+/-7;
      p=0.30).The independent predictors of death at follow-up were: acute myocardial
      infarction (hazard ratio=4.94; 95% confidence interval=2.53-9.64; p<0.001), use
      of beta-blockers (HR=0.34; 95% CI=0.18-0.65; p=0.001), ICD implantation (0.16
      [95% CI=0.05-0.51]; p=0.002), LVEF<25% (HR=2.16; 95% confidence interval 1.25
      3.76; p=0.006), and completeness of revascularization (HR=0.29; 95% CI=0.10-0.82;
      p=0.020). CONCLUSIONS: PCI in patients with LVEF<or=35% is feasible and safe.
      Independent predictors of death at 2-year are occurrence of an acute myocardial
      infarction, treatment by beta blockers, ICD implantation, LVEF<25% and
      completeness of revascularization.

PMID- 18625528
TI  - Brain natriuretic peptide in cardiac surgery--influence of aprotinin.
AB  - BACKGROUND: This study was designed to examine plasma concentrations of BNP and
      its correlations to the perioperative course in patients' cardiopulmonary bypass
      (CPB). METHODS: Sixty-five patients with coronary artery disease (CAD) undergoing
      CPB were examined. Pre, intra and postoperative BNP values and hemodynamic
      parameters were measured. RESULTS: The BNP peak correlated neither with any
      hemodynamic parameters, with the duration of aortic cross-clamping (AXCL), of the
      operation or with CBP-time, nor with the use of catecholamines. BNP values were
      significantly higher with the perioperative use of aprotinin. CONCLUSION: These
      results confirm that the metabolism and biological activity of BNP may differ
      following CPB. An additional reason for increased postoperative BNP values might
      be the use of aprotinin.

PMID- 18625529
TI  - Statins and prevention of atrial fibrillation in patients with heart failure.
AB  - Statins are highly effective and widely used lipid-lowering agents in clinical
      practice, that also display a number of pleiotropic properties beyond cholesterol
      lowering. Several trials have demonstrated that they reduce cardiovascular
      morbidity and mortality in both primary and secondary prevention. Atrial
      fibrillation (AF) and heart failure (HF) represent 2 world-wide epidemics. Recent
      evidence suggests that statins may have beneficial effects on cardiovascular
      outcomes in patients with HF, and specifically in the prevention of AF. The anti
      arrhythmic mechanisms of statins regarding AF prevention in HF patients are not
      fully understood but are possibly related to their pleiotropic effects including
      anti-inflammatory, antioxidant, atrial remodeling attenuation, ion channel
      stabilization, and autonomic nervous system regulation.

PMID- 18625530
TI  - Alpha particle vascular brachytherapy in the treatment of in-stent Restenosis.
AB  - In-stent Restenosis (ISR) is the Achilles heel for using of stent. Vascular
      brachytherapy (VBT) has been the principal scientifically investigated local
      therapy for coronary artery ISR. In our suggested method, a new type of stent,
      which is coated with Boron ((10)B) compound, is used. The coating layer of the
      stent consists of stable isotype of (10)B. Boron Neutron Capture Therapy produced
      alpha particle has enough energy to kill the cells adjacent to the stent, which
      is the site of boron deposition. It would prevent from ISR and intimal
      proliferation. After percutaneous coronary intervention (PCI) and insertion of
      stent, follow-up should be done continuously, and if ISR is detected, BNCT will
      be used to treat the recurrence. Using this modality of VBT would help us to
      overcome the pitfalls in en vogue radiotherapy methods.

PMID- 18625531
TI  - Serum level of pigment epithelium derived factor (PEDF) is an independent
      determinant of resting heart rate in Japanese subjects.
AB  - We have recently found that serum level of pigment epithelium derived factor
      (PEDF) is significantly increased in proportion to the accumulation of the number
      of the components of the metabolic syndrome. Although high heart rate is also
      associated with metabolic risk factors for atherosclerosis, the correlation
      between serum level of PEDF and resting heart rate remains to be elucidated. In
      this study, we examined their relationship in Japanese outpatients. Four hundred
      two consecutive outpatients at Nakamura Clinic (141 male and 261 female; mean age
      74.9+/-9.9) underwent a complete history and physical examination, determination
      of blood chemistries and PEDF levels. In multiple regression analysis, smoking
      (p=0.003), use of beta-blockers (p=0.010, inversely), presence of atrial
      fibrillation (p=0.014), PEDF (p=0.018) and glucose levels (p=0.033) were
      independently correlated to resting heart rate. Further, when mean serum PEDF
      levels were stratified by resting heart rates, a linear and significant trend
      (p=0.025) was observed. The present study demonstrated for the first time that
      serum level of PEDF was one of the independent determinants of resting heart rate
      in Japanese outpatients. PEDF may play some role in sympathetic nerve activity.

PMID- 18625532
TI  - Bioprotective Leuconostoc strains against Listeria monocytogenes in fresh fruits
      and vegetables.
AB  - Ten Leuconostoc mesenteroides and one Ln. citreum strains isolated from fresh
      fruit and vegetables were tested for their antagonistic capacity against Listeria
      monocytogenes. Genetic differences among strains were analyzed by Random
      Amplified Polymorphic DNA (RAPD). All the isolates clustered together and
      differed from the type strain Ln. mesenteroides ATCC 8293 as well as from Ln.
      fallax and Ln. citreum. Organic acids, hydrogen peroxide and bacteriocins were
      detected as main inhibition mechanisms. Characterization of culture supernatants
      from the bacteriocinogenic strains, CM135 and CM160 revealed a high resistance of
      antibacterial activity to temperature and pH, and a bactericidal mode of action
      against L. monocytogenes. Produced bacteriocins belonged to the Class IIa and
      sequencing of genes showed complete homology with mesentericin Y105. A study of
      the effect of the relative dose of pathogen and LAB on control of L.
      monocytogenes in wounds of Golden Delicious apples and Iceberg lettuce leaf cuts
      was performed. A comparison of the dose of bioprotective strain needed for a ten
      fold reduction of the viable pathogen concentration (ED90) revealed that strain
      CM160 was the most effective against L. monocytogenes. ED90 values varied from
      1.3.10(4) to 5.0.10(5) cfu.g(-1) or wound, at ranges of pathogen levels from
      1.0.10(3) to 5.0.10(4) cfu.g(-1) of lettuce or wound of apple. The efficiency of
      the strains was also calculated as the ratio of the ED90 value to the pathogen
      dose inoculated. The lowest ratio was found for strain CM160 at 5 to 50 cells of
      LAB per cell of pathogen. The strain offers potential application for prevention
      of the presence of L. monocytogenes in fresh fruit and vegetables.

PMID- 18625533
TI  - Environment driven cereulide production by emetic strains of Bacillus cereus.
AB  - The impacts of growth media and temperature on production of cereulide, the
      emetic toxin of Bacillus cereus, were measured for seven well characterised
      strains selected for diversity of biochemical and genetic properties and sources
      of origin. All strains carried cereulide synthase gene, ces, on a megaplasmid of
      ca. 200 kb and all grew up to 48-50 degrees C, but produced cereulide only up to
      39 degrees C. On tryptic soy agar five strains, originating from foods, food
      poisonings and environment, produced highest amounts of cereulide at 23 to 28
      degrees C, whereas two strains, from human faeces, produced cereulide similarly
      from 23 to 39 degrees C, with no clear temperature trend. These two strains
      differed from the others also by producing more cereulide on tryptic soy agar if
      supplemented with 5 vol.% of blood, whereas the other five strains produced
      similarly, independent on the presence of blood. On oatmeal agar only one strain
      produced major amounts of cereulide. On skim milk agar, raw milk agar, and
      MacConkey agar most strains grew well but produced only low amounts of cereulide.
      Three media components, the ratio [K+]:[Na+], contents of glycine and [Na+],
      appeared of significance for predicting cereulide production. Increase of
      [K+]:[Na+] (focal variable) predicted (P < 0.001) high cereulide provided that
      the contents of glycine and [Na+] (additional variables) were kept constant. The
      results show that growth medium and temperature up and downregulate cereulide
      production by emetic B. cereus in a complex manner. The relevance of the findings
      to production of cereulide in the gut and to the safety of amino acids as
      additives in foods containing live toxinogenic organisms is discussed.

PMID- 18625534
TI  - UV inactivation and model of UV inactivation of foot-and-mouth disease viruses in
      suspension.
AB  - Foot-and-mouth disease virus (FMDV) causes one of the most contagious diseases
      affecting cloven-hoofed animals (e.g., cattle and swine) and causes severe
      economic loss for many countries. The resistance to UV irradiation of FMDV
      strains isolated from outbreaks in Thailand was investigated in phosphate
      buffered saline at 25 degrees C. Since the regression coefficients of linear
      regression were large and root mean square errors were small, UV inactivation
      could be appropriately summarized and fitted well by a linear equation. The first
      order kinetics then could describe UV inactivation, which was experimentally and
      mathematically shown in this study to be an effective means to inactivate FMDV in
      suspension. The decimal inactivation dose (DID) was modified from D value in
      traditional thermal-inactivation kinetics. The DID was the amount of UV
      irradiation required to reduce the number of microorganisms by a factor of 10, or
      by 90%. DIDs of FMDV serotypes O189, A132, A-Sakol, and AS1 ranged from 19.66 to
      31.31 mWs/cm2. FMDV serotype AS1 was the most UV-resistant, and FMDV serotype
      A132 was the least UV-resistant. UV resistance of FMDV did not vary significantly
      among strains and serotypes (P value > 0.05). DID raw data were used to determine
      the fitted probability distributions by simulation software @Risk. The fitted
      distributions suggested were Exponential, Logistic, Normal, and LogNormal.
      Exponential distribution was the best fit by Chi-square test, Kolmogorov-Smirnov
      test, and Anderson-Darling test (P value >0.10). The parameter beta of the
      Exponential distribution, equivalent to the mean DID, was 24.173 mWs/cm2 as a
      first-order model. Poisson probability distribution described the uncertainty of
      parameter beta for the second-order model. After running simulations of both
      first-order and second-order models, the curves of both first-order and second
      order models were overlaid on the same graph, which indicated that both models
      were only slightly different. This study concluded that FMDV in suspension was
      effectively inactivated by UV irradiation, the fitted probability distribution
      for UV inactivation was Exponential, and source of total uncertainty of this UV
      inactivation model was not the uncertainty component.

PMID- 18625535
TI  - Antibiotic resistance of coagulase-negative staphylococci associated with food
      and used in starter cultures.
AB  - The resistance of 330 coagulase-negative staphylococci (CNS) associated with food
      or used in starter cultures and belonging to the species Staphylococcus carnosus,
      Staphylococcus condimenti, Staphylococcus piscifermentans, Staphylococcus
      equorum, Staphylococcus succinus and Staphylococcus xylosus, against 21
      antibiotics was determined using the disk diffusion method. The incidence and
      number of resistances was found to be species and source of isolation dependent.
      Most strains of S. equorum (63%), S. succinus (90%) and S. xylosus (95%)
      exhibited resistances against up to seven antibiotics, whereas only few strains
      of S. carnosus (12%) and S. piscifermentans (27%) were antibiotic resistant.
      Resistances to lincomycin, penicillin, fusidic acid, oxacillin, ampicillin and
      tetracycline were predominant. Among strains of S. xylosus, the incidence of
      resistance ranged from 22% for tetracycline up to 69% for penicillin. Concerning
      the source of isolation, resistances were often determined in strains of S.
      equorum, S. succinus and S. xylosus isolated from cheese (87%) and sausage (83%),
      and strains of S. xylosus obtained from meat starter cultures (93%). Remarkably,
      all CNS were sensitive to the clinically important antibiotics chloramphenicol,
      clindamycin, cotrimoxazol, gentamicin, kanamycin, linezolid, neomycin,
      streptomycin, synercid and vancomycin. The phenotypic resistances to beta-lactam
      antibiotics, lincomycin and tetracycline were verified by PCR amplification and
      could be traced back to the genes blaZ, lnuA and tetK, respectively. This study
      permitted a comprehensive insight into the incidence of antibiotic resistances in
      food-associated CNS.

PMID- 18625537
TI  - Dermatomyositis induced by drug therapy: a review of case reports.
AB  - BACKGROUND: Drugs have occasionally been implicated in dermatomyositis (DM)
      onset. OBJECTIVE: We sought to review case reports of drug-induced DM. METHODS:
      Articles were gathered from MEDLINE and bibliographies of acquired reports.
      Causality was assessed using World Health Organization criteria. Clinical
      characteristics, management, and resolution were examined. RESULTS: In 70
      reported cases, 50% of patients were female and the median age was 57 years.
      Hydroxyurea was implicated in 51% of cases. All cases had pathognomonic (76%) or
      compatible (24%) cutaneous findings. Hydroxyurea cases lacked myositis, but
      myositis was described in 79.4% of nonhydroxyurea cases. Drug causality was
      probable (25.7%) or possible (74.3%), but not certain in any case. Most patients
      had underlying pathology associated with DM (44% had malignancy; 16% had
      rheumatoid arthritis). Of the sample, 84.3% had improvement of DM after
      discontinuation of the drug. LIMITATIONS: Case reports may emphasize unusual
      findings. CONCLUSIONS: Further work is needed to differentiate drug effects from
      underlying, predisposing factors.

PMID- 18625536
TI  - Does hormone therapy improve age-related skin changes in postmenopausal women? A
      randomized, double-blind, double-dummy, placebo-controlled multicenter study
      assessing the effects of norethindrone acetate and ethinyl estradiol in the
      improvement of mild to moderate age-related skin changes in postmenopausal women.
AB  - BACKGROUND: In postmenopausal women, declining estrogen levels are associated
      with a variety of skin changes, many of which are reportedly improved by estrogen
      supplementation. OBJECTIVE: A study was conducted to assess the effects of
      continuous combined norethindrone acetate (NA) and ethinyl estradiol (EE) in the
      control of mild to moderate age-related skin changes in postmenopausal women.
      METHODS: Four hundred eighty-five subjects were enrolled in this 48-week
      randomized, double-blind study. Subjects were randomized to one of three study
      arms: placebo group (165 subjects), 1 mg NA/5 microg EE group (162 subjects), or
      a 1 mg NA/10 microg EE group (158 subjects). The primary efficacy parameters of
      the study were investigator global assessment of coarse and fine facial wrinkling
      at week 48 and subjective self-assessment of changes in wrinkling from baseline
      at week 48. Secondary parameters included investigator global assessment of skin
      laxity/sagging at week 48, investigator global assessment of skin texture/dryness
      at week 48, patient self-assessment of laxity/sagging, texture/dryness, and
      wrinkle depth determined by image analysis of skin replicas of the periorbital
      (crow's feet) and jowl areas, and skin elasticity determined by timed deformation
      and recoil. RESULTS: There were similar scores in investigator global assessment
      in wrinkling and sagging modules at baseline across all three treatment groups.
      There were slight decreases in all parameters for all treatment groups for the
      primary subject end points, but there were no statistically significant
      differences between the NA/EE groups and placebo. For subject self-assessment of
      overall severity of skin wrinkling, there were no significant changes at weeks 24
      and 48 compared to baseline. These data were unaffected by smoking status or
      alcohol consumption. LIMITATIONS: This study assessed the effects of 48 weeks of
      low-dose estrogen upon facial skin in women who were, on average, 5 years
      postmenopausal. The effects of higher estrogen doses, longer treatment duration,
      or effects upon perimenopausal women cannot be extrapolated from this study.
      CONCLUSION: Low-dose hormone therapy for 48 weeks in postmenopausal women did not
      significantly alter mild to moderate age-related facial skin changes.

PMID- 18625538
TI  - Periocular papules in nephrogenic systemic fibrosis.

PMID- 18625540
TI  - Mini nutritional assessment is a good predictor of functional status in
      institutionalised elderly at risk of malnutrition.
AB  - BACKGROUND & AIMS: To possibly validate the use of Mini Nutritional Assessment
      (MNA) with respect to functional status in institutionalised elderly. METHODS:
      One hundred twenty-three long-term care resident elderly (85.3+/-8.4 years) were
      recruited. Nutritional and functional states were assessed by MNA and Barthel
      Index (BI), respectively. Main inclusion criterion was a MNA<23.5.
      Anthropometric, biochemical data and oral intake (percentage of food consumed to
      that delivered) were evaluated. RESULTS: MNA significantly correlated with BI
      (r=0.55; p<0.0001). Malnutrition (MNA<17) was characterized by lower BMI, muscle
      mass, poor nutritional habits and higher weight loss and disability. Similarly,
      poorer functional status was associated with low BMI, sarcopenia and reduced oral
      intake. The interrelationship between MNA and BI were investigated by multiple
      regression models with progressive inclusion of variables (one/analysis). The
      initial association between MNA and BI (p<0.0001) was masked by weight loss
      (p<0.02), muscle mass (p<0.03) and oral intake (p<0.05). However, when BI was
      included as dependent variable the association with MNA depended on sarcopenia
      (p<0.05) and reduced food consumption (p<0.001). CONCLUSIONS: MNA reliably
      identifies at-risk institutionalised elderly needing higher standards of care,
      particularly related to eating. Routine documentation of oral intakes and feeding
      assistance might be useful to prevent weight loss, sarcopenia and functional
      status deterioration.

PMID- 18625539
TI  - Amines and oximes derived from deoxybenzoins as Helicobacter pylori urease
      inhibitors.
AB  - Twenty amines and oximes from deoxybenzoins were prepared and evaluated for their
      inhibitory activity against Helicobacter pylori urease. Among these compounds,
      high inhibitory activities were observed in amines and oximes, especially amines
      1b (IC(50)=0.011 mM) and 6b (IC(50)=0.047 mM) exhibited good in vitro activities,
      and were comparable to acetohydroxamic acid (AHA). The hydroxyl groups on
      deoxybenzoin skeleton may be responsible for the inhibitory activity and
      coordinate with the nickel (active site) on enzyme. A direct interaction may
      exist between the OH group of hydroxylamines or NH group of amines and His
      alpha323 of H. pylori urease, which is on the flap of the enzyme active site.

PMID- 18625541
TI  - Oral nutritional supplements and taste preferences: 545 days of clinical testing
      in malnourished in-patients.
AB  - BACKGROUND & AIMS: Acceptability and intake of oral nutritional supplements are
      often suboptimal, partly because patients dislike flavour, texture or smell. We
      assessed the taste preferences about milk-based and fruit-juice typed supplements
      in malnourished in-patients. METHODS: One hundred and nine in-patients requiring
      oral nutritional support were assigned to consume four given supplements on four
      consecutive days, to answer a questionnaire based on a 10-point visual analogue
      scale (VAS) on acceptance/tolerance, and to choose their preferred product for
      the fifth day. RESULTS: Overall pleasantness was significantly better for milk
      based supplements than for sweet and salty fruit-juice typed products (on VAS:
      6.2+/-3.1 versus 4.4+/-3.9, p<0.01 and 3.5+/-3.4, p<0.0001, respectively, when 1
      meant "not at all" and 10 "very much"), whereas digestive tolerance was
      comparable. When offered together on day 5, milk-based products were more
      frequently preferred (81.6%) than fruit-juice typed supplements (18.4%, p<0.001).
      Among milk-based products, vanilla, coffee and strawberry had comparable good
      results, whereas chocolate was less chosen and neutral never. For fruit-juice
      typed products, tomato obtained better results than orange or apple. CONCLUSIONS:
      Oral nutritional supplements are globally well-accepted and tolerated, but with
      variations according to categories and flavours that must be considered to
      improve compliance.

PMID- 18625542
TI  - Understanding adjustment following traumatic brain injury: is the Goodness-of-Fit
      coping hypothesis useful?
AB  - Coping efforts have been recognised as an important aspect of resilience
      following traumatic brain injury, but little is known about what constitutes
      effective coping in this population. This longitudinal research examined the
      usefulness of the Goodness-of-Fit hypothesis, drawn from the Lazarus and Folkman
      [(1984). Stress, appraisal and coping. NY: Springer.] theory of stress and
      coping, as a way of understanding coping effectiveness. The hypothesis suggests
      that the nature and success of specific coping strategies will be associated with
      the controllability of the event. If an event is relatively uncontrollable, then
      emotion-focused or perception-focused coping may be more effective than problem
      focused coping. In contrast, a controllable event may be best managed through
      problem-focused coping. Ninety people with traumatic brain injury, drawn from the
      inpatient rehabilitation unit of a major metropolitan hospital in Australia, and
      their relatives participated in this longitudinal study. No support was found for
      the Goodness-of-Fit model, either in the short term or the long term. Although
      the use of problem-focused coping strategies was positively associated with short
      term and long-term role functioning, it was not associated with long-term
      emotional well-being if the situation was perceived to be controllable. The
      findings suggest that the persistent use of problem-focused coping in response to
      the difficulties created by traumatic brain injury can be associated with
      emotional distress in the long term. Reasons for this finding are explored and
      its implications are discussed.

PMID- 18625543
TI  - Influence of fluorinated and hydrogenated nanoparticles on the structure and
      fibrillogenesis of amyloid beta-peptide.
AB  - Peptide aggregation in amyloid fibrils is implicated in the pathogenesis of
      several diseases such as Alzheimer's disease. There is a strong correlation
      between amyloid fibril formation and a decrease in conformational stability of
      the native state. Amyloid-beta peptide (Abeta), the aggregating peptide in
      Alzheimer's disease, is natively unfolded. The deposits found in Alzheimer's
      disease are composed of Abeta fibrillar aggregates rich in beta-sheet structure.
      The influence of fluorinated complexes on the secondary structure and
      fibrillogenesis of Abeta peptide was studied by circular dichroism (CD)
      spectroscopy and transmission electron microscopy (TEM). CD spectra show that
      complexes of polyampholyte and fluorinated dodecanoic acid induce alpha-helix
      structure in Abeta, but their hydrogenated analogous lead to beta-sheet formation
      and aggregation. The fluorinated nanoparticles with highly negative zeta
      potential and hydrophobic fluorinated core have the fundamental characteristics
      to prevent Abeta fibrillogenesis.

PMID- 18625545
TI  - How to tackle bleeding and thrombosis in the newborn.
AB  - Bleeding and its management represent common clinical problems in neonatal
      intensive care, particularly in pre-term infants. Frank and severe single organ
      haemorrhage (e.g. pulmonary or gastrointestinal in association with necrotising
      enterocolitis) is less common, but may require urgent resuscitation and clinical
      stabilisation. Intracranial bleeding is always potentially of greatest concern
      because of the neurological consequences, but the pathophysiological mechanism of
      the most characteristic form, intraventricular haemorrhage, remains incomplete.
      Minor forms of bleeding are commonly seen in sicker neonates, ranging from blood
      stained endotracheal secretions to longer than expected oozing from phlebotomy
      sites, but may be manifestations of disseminated intravascular coagulation. The
      mainstay of treatment for bleeding in association with abnormalities of
      coagulation or thrombocytopenia remains blood products, although their role as
      prophylaxis to prevent bleeding in neonates without clinical signs of haemorrhage
      is less clear. The overwhelming majority of thromboembolic events in neonates
      occur in association with arterial or venous catheters, but the clinical features
      are very variable, including catheter dysfunction and local signs. The optimal
      treatment strategies including use of anticoagulants remain problematic in the
      absence of good clinical trials.

PMID- 18625546
TI  - Reduction of auditory event-related P300 amplitude in subjects with at-risk
      mental state for schizophrenia.
AB  - Neurophysiological methods allow the examination of cognitive-cortical
      functioning in patients with schizophrenia in its prodromal states. As revealed
      by previous studies, event-related potential components such as auditory evoked
      P300 associated with cognitive processes, such as attention and orientation, are
      known to be reduced in amplitude in acute and chronic as well as in medicated and
      unmedicated patients. It is, however, unclear whether a P300 amplitude reduction
      occurs before the schizophrenic psychosis is fully manifested. We studied
      patients in the prodromal phase of the schizophrenic disorder (i.e. subjects with
      an at-risk mental state showing attenuated psychotic symptoms or brief limited
      intermittent symptoms) as well as first-episode patients and chronic patients
      with schizophrenia and compared these groups to healthy subjects. The event
      related P300 was recorded during an auditory oddball paradigm. Groups differed
      significantly from each other in the P300 amplitude at Pz (F(3/149)=2.532,
      p=0.02). Post-hoc tests revealed significantly lower P300 amplitudes of non
      medicated prodromal (p=.03), first-episode (p=.01) and chronic patients (p=.001)
      compared to the healthy controls. The study revealed that there are
      neurophysiological changes as the reduction in P300 amplitudes begins early in
      schizophrenia at the prodromal phase, i.e. before a manifestation of full-blown
      psychosis, and that these changes seem to have a progressive course from
      prodromal to chronic state of schizophrenia as assumed in this cross-sectional
      study.

PMID- 18625544
TI  - Semaphorins and their receptors in lung cancer.
AB  - Semaphorins are a large family of secreted, transmembrane and GPI-linked proteins
      initially characterized in the development of the nervous system and axonal
      guidance. Semaphorins are expressed in many tissues where they regulate normal
      development, organ morphogenesis, immunity and angiogenesis. They affect the
      cytoskeleton, actin filament organization, microtubules and cell adhesion.
      Semaphorin signaling is transduced by plexins, which in the case of most class-3
      semaphorins requires high-affinity neuropilin receptors. The neuropilins also
      function as receptors for VEGF and other growth factors, and their expression is
      often abnormal in tumors. In cancer, semaphorins have both tumor suppressor and
      tumor promoting functions. We review here the current status of semaphorins and
      their receptors in tumor development with a focus on lung cancer.

PMID- 18625547
TI  - Reduced cortical inhibition in first-episode schizophrenia.
AB  - Disturbances in cortico-cortical and cortico-subcortical circuits in
      schizophrenia have been described by previous neuroimaging and
      electrophysiological studies. Transcranial magnetic stimulation (TMS) provides a
      neurophysiological technique for the measurement of cortical excitability,
      especially of the motoneural system. Previous studies using paired-pulse TMS to
      investigate short-interval cortical inhibition (SICI) and intracortical
      facilitation (ICF), mainly involving chronic schizophrenia patients, have been
      inconsistent and only one study in first-episode patients has been conducted so
      far. We assessed SICI (interstimulus interval, ISI, 3 milliseconds, ms) and ICF
      (ISI 7 ms) in 29 first-episode schizophrenia patients (FE-SZ) with limited
      exposure to antipsychotic treatment against measures of 28 healthy controls (HC).
      Amplitudes of motor evoked potentials (MEPs) were measured from the left and
      right first dorsal interosseus muscle (FDI). The conditioning stimulus was set at
      80% intensity of resting motor threshold (RMT) and the test stimulus (TS) was set
      at an intensity that produced an MEP amplitude of about 1 mV. For SICI
      conditions, FE-SZ demonstrated significantly higher MEP amplitudes from left
      motor cortex (right FDI) compared to HC, and for MEPs from right motor cortex
      (left FDI) a similar trend was observable (FE-SZ 41% vs. HC 21% of TS, p=0.017
      for left motor cortex, and FE-SZ 59% vs. HC 31% of TS, p=0.059 for right motor
      cortex; Mann-Whitney U-test). No significant difference in MEPs could be detected
      for ICF on either hemisphere. In addition, there was no difference in left and
      right RMT comparing patients and control subjects. Our result of a reduced SICI
      in a large sample of well characterized first-episode schizophrenia patients
      suggests that a GABAergic deficit may be involved in schizophrenic
      pathophysiology, already early in the disease course, supporting the
      intracortical dysconnectivity hypothesis.

PMID- 18625548
TI  - Proctectomy for rectal cancer in patients with prior spinal cord injury.
AB  - INTRODUCTION: Limited published information is available concerning the clinical
      course of spinal cord injured (SCI) patients who later develop rectal cancer and
      undergo proctectomy. We hypothesized that such patients would have poorer
      outcomes than comparable neurally-intact patients. METHODS: We conducted a
      retrospective study of all SCI veterans receiving care at all Department of
      Veterans Affairs (DVA) Medical Centers who subsequently underwent proctectomy for
      rectal cancer during fiscal years 1993-2002. Only patients with SCI due to trauma
      who met American Spinal Injury Association type A criteria (complete cord injury)
      were analyzed. The search strategy utilized DVA datasets plus data extracted from
      medical records. RESULTS: There were 33,758 patients with ICD-9-CM diagnosis
      codes for SCI and 5246 patients with ICD-9-CM procedure codes for proctectomy due
      to rectal cancer; 72 patients were in both datasets. We received records for 72
      patients and excluded 67 after chart review. Incorrect coding (44) and incomplete
      spinal cord lesions (9) were the most common exclusion criteria. Five patients
      were considered evaluable. The mean age at diagnosis was 65 (range 49-80). All
      five had symptomatic cancers and two (40%) had major comorbidities at admission.
      Postoperative complications occurred in four (80%). The winsorized mean length of
      stay was 28 days. CONCLUSIONS: The complication rate and length of stay for SCI
      patients undergoing proctectomy for rectal cancer were higher than those reported
      for otherwise comparable neurally-intact patients. SCI should be considered a
      risk factor for adverse outcomes in operations for rectal cancer as in other
      major surgery.

PMID- 18625549
TI  - The reuse of spent mushroom compost and coal tailings for energy recovery:
      comparison of thermal treatment technologies.
AB  - Thermal treatment technologies were compared to determine an appropriate method
      of recovering energy from two wastes - spent mushroom compost and coal tailings.
      The raw compost and pellets of these wastes were combusted in a fluidised-bed and
      a packed-bed, and contrasted to pyrolysis and gasification. Quantitative
      combustion parameters were compared to assess the differences in efficiency
      between the technologies. Fluidised-bed combustion was more efficient than the
      packed-bed in both instances and pellet combustion was superior to that of the
      compost alone. Acid gas emissions (NO(x), SO(x) and HCl) were minimal for the
      fluidised-bed, thus little gas cleaning would be required. The fuels' high ash
      content (34%) also suggests fluidised-bed combustion would be preferred. The
      Alkali Index of the ash indicates the possibility of fouling/slagging within the
      system, caused by the presence of alkali metal oxides. Pyrolysis produced a range
      of low-calorific value-products, while gasification was not successful.

PMID- 18625550
TI  - Biomimetic synthesis and characterisation of protein capped silver nanoparticles.
AB  - A controlled and up-scalable route for the biosynthesis of silver nanopartilces
      (NPs) mediated by fungal proteins of Coriolus versicolor has been undertaken for
      the first time. The fungus when challenged with silver nitrate solution
      accumulated silver NPs on its surface in 72h which could be reduced to 1h by
      tailoring the reaction conditions. Under alkaline conditions, the reaction was
      much faster and could easily proceed at room temperature even without stirring.
      The resulting Ag NPs displayed controllable structural and optical properties
      depending on the experimental parameters such as pH and reaction temperatures.
      The average size, morphology, and structure of particles were determined by AFM,
      TEM, XRD and UV/Visible absorption spectrophotometry. Fourier transform infrared
      study disclosed that the amino groups were bound to the particles, which was
      accountable for the stability of NPs. It further confirmed the presence of
      protein as the stabilizing and capping agent surrounding the silver NPs.
      Experiments were conducted both with, media in which fungus was initially
      harvested and that of pristine fungal mycelium alone. Under normal conditions, in
      the case of media extracellular synthesis took place whereby other than the
      fungal proteins, glucose was also responsible for the reduction. In the case of
      fungal mycelium, the intracellular formation of Ag NPs, could be tailored to give
      both intracellular and extracellular Ag NPs under alkaline conditions whereby the
      surface S-H groups of the fungus played a major role.

PMID- 18625551
TI  - Comparison of odour emission rates measured from various sources using two
      sampling devices.
AB  - Two commonly used sampling devices (a wind tunnel and the US EPA dynamic emission
      chamber), were used to collect paired samples of odorous air from a number of
      agricultural odour sources. The odour samples were assessed using triangular,
      forced-choice dynamic olfactometry. The odour concentration data was combined
      with the flushing rate data to calculate odour emission rates for both devices on
      all sources. Odour concentrations were consistently higher in samples collected
      with a flux chamber (ratio ranging from 10:7 to 5:1, relative to wind tunnel
      samples), whereas odour emission rates were consistently larger when derived from
      wind tunnels (ratio ranging from 60:1 to 240:1, relative to flux chamber values).
      A complex relationship existed between emission rate estimates derived from each
      device, apparently influenced by the nature of the emitting surface. These
      results have great significance for users of odour dispersion models, for which
      an odour emission rate is a key input parameter.

PMID- 18625552
TI  - 4-(1,3-Thiazol-2-yl)morpholine derivatives as inhibitors of phosphoinositide 3
      kinase.
AB  - 4-(1,3-Thiazol-2-yl)morpholine derivatives have been identified as potent and
      selective inhibitors of phosphoinositide 3-kinase. The SAR data of selected
      examples are presented and the in vivo profiling of compound 18 is shown to
      demonstrate the utility of this class of compounds in xenograft models of tumor
      growth.

PMID- 18625553
TI  - N-Acyl-3-amino-5H-furanone derivatives as new inhibitors of LuxR-dependent quorum
      sensing: Synthesis, biological evaluation and binding mode study.
AB  - New N-acyl homoserine lactone analogues, N-acyl-3-amino-5H-furanone derivatives
      and some 4-halogeno counterparts, were synthesised and tested for their ability
      to modulate LuxR-dependent bacterial quorum sensing. Both types of analogues
      proved to be inhibitors, the halogenated compounds being significantly more
      active. Molecular modelling suggested that the conjugated enamide group induces
      two preferential conformations leading to specific binding modes. In addition,
      the presence of the halogen atom could enhance the fitting of the lactone ring
      through specific interactions with strictly conserved or conservatively
      replaceable residues in the LuxR protein family, namely Asp79, Trp94 and Ile81.

PMID- 18625554
TI  - Discovery of triazolinone non-nucleoside inhibitors of HIV reverse transcriptase.
AB  - Novel non-nucleoside inhibitors of HIV-RT that contain pyridazinone isosteres
      were prepared, and a series of triazolinones were found to be potent inhibitors
      of HIV replication. These compounds were active against several NNRTI-resistant
      virus strains. Pharmacokinetic studies indicated that inhibitor 7e has good
      bioavailability in rats. Several fragments of inhibitor 7c were prepared, and the
      binding of these compounds to HIV-RT was analyzed by surface plasmon resonance
      spectroscopy.

PMID- 18625555
TI  - Effects of N-pyrrole substitution on the anti-biofilm activities of oroidin
      derivatives against Acinetobacter baumannii.
AB  - Bacteria of the genus Acinetobacter spp. are rapidly emerging as problematic
      pathogens in healthcare settings. This is exacerbated by the bacteria's ability
      to form robust biofilms. Marine natural products incorporating a 2-aminoimidazole
      (2-AI) motif, namely from the oroidin class of marine alkaloids, have served as a
      unique scaffold for developing molecules that have the ability to inhibit and
      disperse bacterial biofilms. Herein we present the anti-biofilm activity of a
      small library of second generation oroidin analogues against the bacterium
      Acinetobacter baumannii.

PMID- 18625556
TI  - Synthesis and evaluation of alpha,alpha'-disubstituted phenylacetate derivatives
      for T-type calcium channel blockers.
AB  - We have synthesized and evaluated alpha,alpha'-disubstituted phenylacetate
      derivatives that were designed as T-type calcium channel blockers. Among them,
      compound 10e (IC(50)=8.17+/-0.48nM) showed the most potent T-type calcium current
      blocking activity and higher potency than Mibefradil (IC(50)=1.34+/-0.49microM).
      The PK profile and subtype selectivity over L-type calcium channel were satisfied
      for further animal assay using disease model.

PMID- 18625557
TI  - N-Benzyl-N-(pyrrolidin-3-yl)carboxamides as a new class of selective dual
      serotonin/noradrenaline reuptake inhibitors.
AB  - The structure-activity relationship and the synthesis of novel N-benzyl-N
      (pyrrolidin-3-yl)carboxamides as dual serotonin (5-HT) and noradrenaline (NA)
      monoamine reuptake inhibitors are described. Compounds such as 18 exhibited dual
      5-HT and NA reuptake inhibition, good selectivity over dopamine (DA) reuptake
      inhibition and drug-like physicochemical properties consistent with CNS target
      space. Compound 18 was selected for further preclinical evaluation.

PMID- 18625558
TI  - Red light-activated phosphorothioate oligodeoxyribonucleotides.
AB  - Hairpin-structured phosphorothioate oligodeoxyribonucleotides containing a
      singlet oxygen-sensitive linker in the loop were prepared. These compounds do not
      bind complementary nucleic acids in the dark. Upon irradiation with red light in
      the presence of chlorine e6 the linker within these compounds is cleaved and a
      single-stranded oligodeoxyribonucleotide is produced. The latter compound is an
      efficient binder of complementary nucleic acids. This is the first example of
      'caged' phosphorothioate oligodeoxyribonucleotides, whose nucleic acid binding
      ability is triggered by red light.

PMID- 18625559
TI  - Design and synthesis of novel oxazole containing 1,3-dioxane-2-carboxylic acid
      derivatives as PPAR alpha/gamma dual agonists.
AB  - A few novel 1,3-dioxane carboxylic acid derivatives were designed and synthesized
      to aid in the characterization of PPAR alpha/gamma dual agonists. Structural
      requirements for PPARalpha/gamma dual agonism of 1,3-dioxane carboxylic acid
      derivatives included the structural similarity with potent glitazones in fibric
      acid chemotype. The compounds with this pharmacophore and substituted oxazole as
      a lipophilic heterocyclic tail were synthesized and evaluated for their in vitro
      PPAR agonistic potential and in vivo hypoglycemic and hypolipidemic efficacy in
      animal models. Lead compound 2-methyl-c-5-[4-(5-methyl-2-(4-methylphenyl)-oxazol
      4-ylmethoxy)-benzyl]-1,3-dioxane-r-2-carboxylic acid 13b exhibited potent
      hypoglycemic, hypolipidemic and insulin sensitizing effects in db/db mice and
      Zucker fa/fa rats.

PMID- 18625560
TI  - Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues
      as TNF-alpha and IL-6 inhibitors.
AB  - In the present article, we have synthesized three different series of
      pyrazolo[3,4-b]pyridines and their structural analogues using novel synthetic
      strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2
      formyl-3,4,6-tri-O-methyl-D-glucal/chromone-3-carbaldehyde with heteroaromatic
      amines. All synthesized compounds were evaluated for their anti-inflammatory
      activity against TNF-alpha and IL-6. Out of 28 compounds screened, 40, 51, 52 and
      56 exhibited promising activity against IL-6 with 60-65% inhibition at 10 microM
      concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory
      activity with IC(50)'s of 0.2, 0.3 and 0.16 microM, respectively. Compound 56 was
      not cytotoxic in CCK-8 cells up to the concentration of >100 microM.

PMID- 18625561
TI  - Syntheses of phosphatidyl-beta-D-glucoside analogues to probe antigen selectivity
      of monoclonal antibody 'DIM21'.
AB  - Herein, we report the chemical syntheses of a series of phosphatidyl-beta-D
      glucoside (PtdGlc) analogues, including 6-O-Ac, sn-2-O-Me, phosphorothioate as
      well as phosphatidylgalactoside and -mannoside derivatives. In the key step, beta
      glycosyl H-phosphonate was condensed with enantiomerically pure diacylglycerol.
      Comparison of spectroscopic data with mono-acetylated PtdGlc from natural source
      confirmed the presence of an acetyl moiety at position 6. Furthermore, the
      reactivity of PtdGlc and its analogues toward monoclonal antibody 'DIM21' (MAb
      DIM21) was evaluated, revealing the crucial structural antigen features for
      successful MAb DIM21 binding.

PMID- 18625562
TI  - Molecular features of the prazosin molecule required for activation of Transport
      P.
AB  - Closely related structural analogues of prazosin have been synthesised and tested
      for inhibition and activation of Transport-P in order to identify the structural
      features of the prazosin molecule that appear to be necessary for activation of
      Transport-P. So far, all the compounds tested are less active than prazosin. It
      is shown that the structure of prazosin appears to be very specific for the
      activation. Only quinazolines have been found to activate, and the presence of
      the 6,7-dimethoxy and 4-amino groups appears to be critically important.

PMID- 18625563
TI  - Speculations on the emergence of self-awareness in big-brained organisms: the
      roles of associative memory and learning, existential and religious questions,
      and the emergence of tautologies.
AB  - This paper argues that self-awareness emerges in organisms whose brains have a
      sufficiently integrated, complex ability for associative learning and memory.
      Continual sensory input of information related to the organism leads to the
      formation of a set of associations that may be termed an organismal "self-image".
      After providing the basic mechanistic basis for the emergence of an organismal
      self-image, this paper proceeds to go through a representative list of behaviors
      associated with self-awareness, and shows how associative memory and learning,
      combined with an organismal self-image, leads to the emergence of these various
      behaviors. This paper also discusses various tautologies that invariably emerge
      when discussing self-awareness. We continue with various speculations on
      manipulating self-awareness, and discuss how concepts from set and logic theory
      may provide a useful set of tools for understanding the emergence of higher
      cognitive functions in complex organisms.

PMID- 18625564
TI  - Modality-independent processes in cued motor preparation revealed by cortical
      potentials.
AB  - We used event-related potentials (ERPs) in a crossmodal stimulus-response
      compatibility paradigm to identify modality-independent aspects of rule
      processing and cued response facilitation. Participants responded to a
      lateralized target with the ipsilateral (compatible) or contralateral
      (incompatible) hand. Cue-target modality and cue-target order were manipulated.
      The cue preceded the target in half of the trials, and the target preceded the
      cue in the other half. For half of the participants, a visual cue signalled the
      response rule to an auditory target, while in other half, an auditory cue
      signalled the response rule to a visual target. Behavioural results showed a
      significant cue facilitation effect with response times faster for trials when
      the cue preceded the target, regardless of cue-target modality. The overall
      fastest response times were obtained in auditory cue-visual target trials. We
      performed groupwise independent component analysis of the cortical potentials and
      identified two modality-independent spatiotemporal patterns related to
      experimental effects. The first pattern, which resembled the early part of a
      contingent-negative waveform, was associated with response rule processing,
      regardless of cue-target presentation order and modality. The second pattern
      showed amplitude modulations that were dependent on stimulus modality. However,
      this pattern also correlated with faster response times only when the cue
      preceded the target and regardless of cue-target modality. Source analysis
      suggested that the response rule processing pattern originated from the posterior
      parietal, motor and cingulate regions. The pattern associated with the cue-first
      facilitation effect originated from cingulate and medial frontal regions. The
      effects carried by both patterns showed temporal overlap in the interval between
      the first and second stimulus presentation, but with differences in their
      relation to response rule processing and behavioural facilitation.

PMID- 18625565
TI  - Prostate tumor alignment and continuous, real-time adaptive radiation therapy
      using electromagnetic fiducials: clinical and cost-utility analyses.
AB  - OBJECTIVE: To evaluate the accuracy, utility, and cost effectiveness of a new
      electromagnetic patient positioning and continuous, real-time monitoring system,
      which uses permanently implanted resonant transponders in the target (Calypso 4D
      Localization System and Beacon transponders, Seattle, WA) to continuously monitor
      tumor location and movement during external beam radiation therapy of the
      prostate. MATERIALS AND METHODS: This clinical trial studied 43 patients at 5
      sites. All patients were implanted with 3 transponders each. In 41 patients, the
      system was used for initial alignment at each therapy session. Thirty-five
      patients had continuous monitoring during their radiation treatment. Over 1,000
      alignment comparisons were made to a commercially available kV X-ray positioning
      system (BrainLAB ExacTrac, Munich, Germany). Using decision analysis and Markov
      processes, the outcomes of patients were simulated over a 5-year period and
      measured in terms of costs from a payer's perspective and quality-adjusted life
      years (QALYs). RESULTS: All patients had satisfactory transponder implantations
      for monitoring purposes. In over 75% of the treatment sessions, the correction to
      conventional positioning (laser and tattoos) directed by an electromagnetic
      patient positioning and monitoring system was greater than 5 mm. Ninety-seven
      percent (34/35) of the patients who underwent continuous monitoring had target
      motion that exceeded preset limits at some point during the course of their
      radiation therapy. Exceeding preset thresholds resulted in user intervention at
      least once during the therapy in 80% of the patients (28/35). Compared with
      localization using ultrasound, electronic portal imaging devices (EPID), or
      computed tomography (CT), localization with the electromagnetic patient
      positioning and monitoring system yielded superior gains in QALYs at comparable
      costs. CONCLUSIONS: Most patients positioned with conventional tattoos and lasers
      for prostate radiation therapy were found by use of the electromagnetic patient
      positioning and monitoring system to have alignment errors exceeding 5 mm. Almost
      all patients undergoing external beam radiation of the prostate have been shown
      to have target organ movement exceeding 3 mm during radiation therapy delivery.
      The ability of the electromagnetic technology to monitor tumor target location
      during the same time as radiation therapy is being delivered allows clinicians to
      provide real time adaptive radiation therapy for prostate cancer. This permits
      clinicians to intervene when the prostate moves outside the radiation isocenter,
      which should decrease adverse events and improve patient outcomes. Additionally,
      a cost-utility analysis has demonstrated that the electromagnetic patient
      positioning and monitoring system offers patient outcome benefits at a cost that
      falls well within the payer's customary willingness to pay (WTP) threshold of
      $50,000 per QALY.

PMID- 18625566
TI  - Prostate carcinoma spatial distribution patterns in Chinese men investigated with
      systematic transperineal ultrasound guided 11-region biopsy.
AB  - OBJECTIVES: To evaluate prostate cancer spatial distribution patterns with
      transperineal ultrasound navigated 11-region prostate biopsy template in a
      Chinese screening population. METHODS: From May 2004 to December 2007, 215
      patients with a median prostate-specific antigen (PSA) level of 21.0 ng/ml were
      diagnosed with prostate cancer through transperineal ultrasound guided 11-region
      template prostate biopsy at Peking Union Medical College Hospital. The
      characteristics of our sample cancer spatial distribution were assessed in
      relation with different PSA levels. RESULTS: The mean positives for the cancer of
      regions 1-10 and region 11 (the apical region) were 61.2% vs. 66.4% in patients
      whose PSA > 20 ng/ml (P = 0.29), and 35.7% vs. 47.6% in patients with PSA <or= 20
      ng/ml (P = 0.001). The positives for cancer contained within the anterior and
      posterior parts were 96.5% vs. 90.9% (P = 0.10) in patients with PSA > 20 ng/ml
      and 75.2% vs. 75.2% in patients with PSA <or= 20 ng/ml (P = 1.00). CONCLUSIONS:
      The current study suggests that prostate carcinoma foci are more frequently
      localized in the apical region in patients with normal to moderately increased
      PSA. Special attention should be paid to the apical region during the selection
      process of biopsy regions for this group of patients.

PMID- 18625568
TI  - The impact of marriage on bladder cancer mortality.
AB  - OBJECTIVES: Marital status has been found to influence survival in a number of
      malignancies. We examined data from the Surveillance, Epidemiology, and End
      Results (SEER) cancer survival database to see if married patients with bladder
      cancer had a survival advantage vs. nonmarried patients. METHODS: The SEER
      database contains data on 127,015 patients diagnosed with bladder cancer between
      1973 and 2002. Using multivariate Cox proportional hazard regression analyses, we
      examined the impact of marital status (single, married, separated, divorced, or
      widowed) on survival after diagnosis with bladder cancer. Age, race, AJCC stage,
      radiation and chemotherapy, and cystectomy were other variables analyzed.
      RESULTS: Marital status did not appear to have a significant survival effect for
      women. However, men who were widowed had a risk of death of 1.74 relative to
      married men (95% CI 1.15, 2.26, P = 0.008). For widowed men over 70, this effect
      was even more pronounced, with a risk of death of 2.1 (95% CI 1.33, 3.31, P =
      0.001). CONCLUSIONS: While we did not see any definite survival advantage to
      being married vs. not being married for patients who are diagnosed with bladder
      cancer, there is a significant risk to widowed men, particularly older widowed
      men. This risk is independent of age, race, stage, and may reflect the patient's
      willingness to seek medical treatment in addition to psychoneuroimmune factors.

PMID- 18625567
TI  - Association of chromosomal locus 8q24 and risk of prostate cancer: a hospital
      based study of German patients treated with brachytherapy.
AB  - BACKGROUND: Genetic susceptibility contributes to the risk of prostate cancer but
      the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24
      have emerged as possible risk factors for breast and prostate cancer from genome
      wide association studies. OBJECTIVE: We aimed to define the risks associated with
      two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital
      based series of prostate cancer patients treated with brachytherapy. MATERIAL AND
      METHODS: We analyzed genomic DNA samples of 488 prostate cancer cases undergoing
      brachytherapy at Hannover Medical School, and of 462 male controls from the same
      location. Genotyping was performed using 5'-exonuclease allelic discrimination
      assays, and results were evaluated with chi(2) tests and logistic regression
      analyses. RESULTS: We investigated whether rs1447295 and rs13281615 are
      associated with disease risk in a hospital-based prostate cancer case-control
      series from Northern Germany. The rare allele of rs1447295 was observed at higher
      frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P =
      0.01), and there was a dose-dependent trend towards a higher prevalence of
      heterozygous and homozygous carriers among the prostate cancer patients (per
      allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of
      rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI
      0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was
      significantly different between cases and controls (P = 0.01). CONCLUSION: Our
      results corroborate previous reports of 8q24 as a prostate cancer susceptibility
      locus and provide evidence for rs1447295 as a potentially important genetic
      marker. Further studies are required to confirm whether the adjacent breast
      cancer-associated variant rs13281615 may be inversely associated with prostate
      cancer risk.

PMID- 18625569
TI  - EGFR mutation in kidney carcinoma confers sensitivity to gefitinib treatment: a
      case report.
AB  - Mutations of the epidermal growth factor receptor (EGFR) gene are known to be
      associated with the pronounced tumor response to EGFR tyrosine kinase inhibitors
      (TKI). Unfortunately, these TKI-sensitizing alterations have been detected almost
      exclusively in lung adenocarcinomas; indeed, their occurrence in tumors of other
      histologic types or other organs is exceptionally rare. Here we report a case of
      intragenic EGFR microdeletion in renal cell carcinoma (RCC) associated with the
      effect of treatment by gefitinib. Patient G., 60 years old, underwent radical
      surgery for clear cell RCC, however local relapse and metastatic lesions in the
      lungs were revealed 33 months later. The patient was successfully treated by
      interleukin-2 (first line therapy), tamoxifen (second line), and interferon-alpha
      (third line). After disease progression, EGFR mutation test was performed as a
      compassionate attempt. It revealed "classical" 15 base pair deletion, so
      gefitinib was administered. This treatment led to a dramatic symptomatic response
      within the first week of therapy; reduction of dyspnea was so evident that it
      allowed the patient to return to work. Clinical examination demonstrated
      significant improvement with respect to pleuritis and pericarditis. The duration
      of tumor response, which was classified as disease stabilization, was equal to 4
      months. This case report suggests that kidney tumors have to be investigated more
      closely with respect to the occurrence of TKI-sensitizing EGFR mutations.

PMID- 18625570
TI  - A single institution experience with biochemical recurrence after radical
      prostatectomy for tumors that on pathology are of small volume or
      "insignificant".
AB  - OBJECTIVE: Small volume prostate cancers (<0.5 cc, svPC), and insignificant
      prostate cancers (<0.5 cc and Gleason scores <7, InsigPC) are considered
      clinically insignificant by some investigators. The aim of this study is to
      determine the biochemical recurrence rate (BCR) of svPC and InsigPC in
      prostatectomy specimens. METHODS: In total, 502 patients with prostate cancer,
      treated with radical prostatectomy (RP) between 1992 and 2005 and with detailed
      pathological classification, were included in the present study. Patients were
      postoperatively followed for a median period of 39.5 months (0.6-150). A total of
      82 specimens (16.3%) with svPC including 64 (12.8%) with InsigPC were identified.
      BCR was defined as 2 consecutive PSA levels >0.10 ng/ml. RESULTS: In the total
      group, the median age at the time of surgery was 62.7 years (42.4-73.4) and the
      median preoperative PSA level was 8.0 ng/ml. Patients with InsigPC had Gleason
      scores of 4 in 7%, 5 in 37%, and 6 in 56%. Positive surgical margins were
      identified in 13 (15.9%) svPC and in 8 (12.7%) InsigPC specimens. The 5-year risk
      of BCR for the svPC group and the insigPC group was 10% (95% CI 2-18%, 7 and 5
      patients, respectively) vs. 35% (95% CI 29-41%) in the rest of the cohort (log
      rank P = 0.001). CONCLUSION: Patients with svPC and patients with InsigPC have a
      significantly lower risk of BCR. However, even in this seemingly very favorable
      patient group, 1 in 10 patients will develop a BCR after RP. Therefore, new
      studies are needed to examine what the prognostic relevance is of small-volume
      tumors.

PMID- 18625571
TI  - Plaque biology: interesting science or pharmacological treasure trove?
AB  - Our understanding of the events that occur within atherosclerotic plaques has
      improved dramatically over the last 2 decades, particularly with regard to the
      role of plaque destabilisation and the onset of clinical ischaemic syndromes.
      Many potential targets have been identified for therapeutic intervention aimed at
      disease prevention, plaque stabilisation and regression. Furthermore, many
      potential biomarkers of vascular disease have generated interest in terms of
      monitoring disease activity and the effect of therapeutic agents. However,
      despite much scientific promise with in vitro cell and animal models, there has
      been much less success in modulation of these processes in clinical practice.
      This review will highlight the local and systemic factors associated with disease
      progression and acute plaque destabilisation, the current role of therapeutic
      agents and the potential for targeted plaque modification.

PMID- 18625572
TI  - Corticosteroid treatment of behaviour, language and motor regression in childhood
      disintegrative disorder.
AB  - Childhood disintegrative disorder (CDD) (ICD-10 F84.3) is defined by a period of
      normal development before onset followed by gradual loss of previously acquired
      skills with the development of characteristic abnormalities of social,
      communicative and behavioural functioning. We report two children with apparent
      CDD, who showed amelioration of behaviour, language and motor regression after
      corticosteroid treatment.

PMID- 18625573
TI  - Optimal k-space sampling for single point imaging of transient systems.
AB  - A novel approach for sampling k-space in a pure phase encoding imaging sequence
      is presented using the Single Point Imaging (SPI) technique. The sequence is
      optimised with respect to the achievable Signal-to-Noise ratio (SNR) for a given
      time interval via selective sparse k-space sampling, dictated by prior knowledge
      of the overall object of interest's shape. This allows dynamic processes
      featuring short T(2)( *) NMR signal to be more readily followed, in our case the
      absorption of moisture by a cereal-based wafer material. Further improvements in
      image quality are also shown via the use of complete sampling of k-space at the
      start or end of the series of imaging experiments; followed by subsequent use of
      this data for un-sampled k-space points as opposed to zero filling.

PMID- 18625574
TI  - Effect of reaction vessel diameter on sonochemical efficiency and cavitation
      dynamics.
AB  - The influence of reaction vessel diameter on the sonochemical yield was
      investigated by using reaction vessels with five different diameters. It was
      revealed that the formation of H(2)O(2) and chloride ion, from the sonolysis of
      pure water and 1,2,4-trichlorobenzene aqueous solution, was affected by the
      reaction vessel diameter. That is, these yields increased as the reaction vessel
      diameter increased up to o 90 mm and then decreased over o 90 mm. From the
      analyses of the measurement of sonochemiluminescence and the calorimetry, it was
      suggested that active cavitation bubbles were formed at certain zones. In the
      case of a larger diameter reaction vessel, it was suggested that bubble nuclei
      that have not grown up to the resonance size, escaped from the sonication zone to
      the non-sonication zone and dissolved away. As a result, the number of active
      cavitation bubbles and the yields of H(2)O(2) and chloride ion would decrease in
      the case of a larger diameter reaction vessel.

PMID- 18625575
TI  - Multiple digital squamous cell carcinoma due to 'soluble-oil'.

PMID- 18625576
TI  - Reconstruction of hand skin defects by microdissected mini anterolataral thigh
      perforator flaps.
AB  - SUMMARY: Three cases of traumatic skin defect and two cases of secondary skin
      defect after releasing scar contractures on the dorsum or palm of the hand,
      except for the fingers and thumb, were successfully reconstructed with the use of
      microdissected thin anterolateral thigh perforator flaps. This particular type of
      reconstruction needs thin, small flap coverage with a reliable blood supply from
      a long vascular pedicle. Microdissection of the perforator enables the
      distribution of vessels towards the thin layer of adipose tissue to be identified
      and the vessel in the deep adipose layer to be used as an additional pedicle
      vessel. Therefore, a small and thin flap can be elevated accurately with a longer
      vascular pedicle than is possible with the conventional method of flap elevation.

PMID- 18625577
TI  - Osteocyte morphology in fibula and calvaria --- is there a role for
      mechanosensing?
AB  - INTRODUCTION: External mechanical forces on cells are known to influence
      cytoskeletal structure and thus cell shape. Mechanical loading in long bones is
      unidirectional along their long axes, whereas the calvariae are loaded at much
      lower amplitudes in different directions. We hypothesised that if osteocytes, the
      putative bone mechanosensors, can indeed sense matrix strains directly via their
      cytoskeleton, the 3D shape and the long axes of osteocytes in fibulae and
      calvariae will bear alignment to the different mechanical loading patterns in the
      two types of bone. MATERIALS AND METHODS: We used confocal laser scanning
      microscopy and nano-computed tomography to quantitatively determine the 3D
      morphology and alignment of long axes of osteocytes and osteocyte lacunae in
      situ. RESULTS: Fibular osteocytes showed a relatively elongated morphology (ratio
      lengths 5.9:1.5:1), whereas calvarial osteocytes were relatively spherical (ratio
      lengths 2.1:1.3:1). Osteocyte lacunae in fibulae had higher unidirectional
      alignment than the osteocyte lacunae in calvariae as demonstrated by their degree
      of anisotropy (3.33 and 2.10, respectively). The long axes of osteocyte lacunae
      in fibulae were aligned parallel to the principle mechanical loading direction,
      whereas those of calvarial osteocyte lacunae were not aligned in any particular
      direction. CONCLUSIONS: The anisotropy of osteocytes and their alignment to the
      local mechanical loading condition suggest that these cells are able to directly
      sense matrix strains due to external loading of bone. This reinforces the widely
      accepted role of osteocytes as mechanosensors, and suggests an additional mode of
      mechanosensing besides interstitial fluid flow. The relatively spherical
      morphology of calvarial osteocytes suggests that these cells are more
      mechanosensitive than fibular osteocytes, which provides a possible explanation
      of efficient physiological load bearing for the maintenance of calvarial bone
      despite its condition of relative mechanical disuse.

PMID- 18625578
TI  - Science communication. Interactions with the mass media.

PMID- 18625579
TI  - An appraisal of the strengths and weaknesses of newborn and juvenile rat models
      for researching gastrointestinal development.
AB  - Research on the impact of bioactive compounds on the development and functional
      maturation of the gastrointestinal (GI) tract using newborn and juvenile rats has
      greatly contributed to the knowledge of GI physiology and to the improved
      clinical management of both premature and full-term newborns. Of the animal
      models available, two types have been described for use with young rats-
      maintenance models and substitution models. Maintenance models are those in which
      the young are reared with the dam and therefore benefit from continuation of
      natural nutrition and maternal care. Substitution models are those in which the
      young are reared in the absence of the dam using artificially formulated milk
      delivered by various means into specific GI sites. In this review, we describe
      these models and their operation, and discuss the strengths and weaknesses of
      each. Attention is also given to questions of scientific validity and some animal
      welfare issues raised by the use of these models.

PMID- 18625580
TI  - In vivo magnetic resonance imaging of animal models of knee osteoarthritis.
AB  - Recent technical developments in high-field magnetic resonance (MR) scanners,
      improvement in radio frequency coil design and gradient performance along with
      the development of efficient pulse sequences and new methods of enhancing
      contrast have made high-quality imaging of animal arthritis models feasible. MR
      can provide high-resolution structural information about the osteoarthritic
      changes in animal models, and also information about the biophysical properties
      of cartilage. This paper reviews the MR techniques available for animal knee
      imaging, and the various MR-derived readouts of knee osteoarthritis in animal
      models. Pitfalls in interpreting animal joint anatomy and joint composition are
      highlighted.

PMID- 18625581
TI  - The use of mice and rats as animal models for cardiopulmonary resuscitation
      research.
AB  - Cardiopulmonary resuscitation (CPR) after the induction of cardiac arrest (CA)
      has been studied in mice and rats. The anatomical and physiological parameters of
      the cardiopulmonary system of these two species have been defined during
      experimental studies and are comparable with those of humans. Moreover, these
      animal models are more ethical to establish and are easier to manipulate, when
      compared with larger experimental animals. Accordingly, the effects of successful
      CPR on the function of vital organs, such as the brain, have been investigated
      because damage to these vital organs is of concern in CA survivors. Furthermore,
      the efficacy of several drugs, such as adrenaline (epinephrine), vasopressin and
      nitroglycerin, has been evaluated for use in CA in these small animal models. The
      purpose of these studies is not only to increase the rate of survival of CA
      victims, but also to improve their quality of life by reducing damage to their
      vital organs after CA and during CPR.

PMID- 18625582
TI  - Animal welfare and the refinement of neuroscience research methods--a case study
      of Huntington's disease models.
AB  - The use of animals in biomedical and other research presents an ethical dilemma:
      we do not want to lose scientific benefits, nor do we want to cause laboratory
      animals to suffer. Scientists often refer to the potential human benefits of
      animal models to justify their use. However, even if this is accepted, it still
      needs to be argued that the same benefits could not have been achieved with a
      mitigated impact on animal welfare. Reducing the adverse effects of scientific
      protocols ('refinement') is therefore crucial in animal-based research. It is
      especially important that researchers share knowledge on how to avoid causing
      unnecessary suffering. We have previously demonstrated that even in studies in
      which animal use leads to spontaneous death, scientists often fail to report
      measures to minimize animal distress (Olsson et al. 2007). In this paper, we
      present the full results of a case study examining reports, published in peer
      reviewed journals between 2003 and 2004, of experiments employing animal models
      to study the neurodegenerative disorder Huntington's disease. In 51 references,
      experiments in which animals were expected to develop motor deficits so severe
      that they would have difficulty eating and drinking normally were conducted, yet
      only three references were made to housing adaptation to facilitate food and
      water intake. Experiments including end-stages of the disease were reported in 14
      papers, yet of these only six referred to the euthanasia of moribund animals. If
      the reference in scientific publications reflects the actual application of
      refinement, researchers do not follow the 3Rs (replacement, reduction,
      refinement) principle. While in some cases, it is clear that less-than-optimal
      techniques were used, we recognize that scientists may apply refinement without
      referring to it; however, if they do not include such information in
      publications, it suggests they find it less relevant. Journal publishing policy
      could play an important role: first, in ensuring that referees seriously consider
      whether submitted studies were indeed carried out with the smallest achievable
      negative impact on the animals and, secondly, in encouraging scientists to share
      refinements through the inclusion of a 3Rs section in papers publishing the
      results of animal-based research.

PMID- 18625583
TI  - Refinement: promoting the three Rs in practice.
AB  - Refinement of scientific procedures carried out on protected animals is an
      iterative process, which begins with a critical evaluation of practice. The
      process continues with objective assessment of the impact of the procedures,
      identification of areas for improvement, selection and implementation of an
      improvement strategy and evaluation of the results to determine whether there has
      been the desired effect, completing the refinement loop and resulting in the
      perpetuation of good practice. Refinements may be science-driven (those which
      facilitate getting high-quality results) or welfare-driven or may encompass both
      groups, but whatever the driver, refinements almost always result in benefits to
      both welfare and science. Refinements can be implemented in all aspects of animal
      use: improved methodology in invasive techniques, housing and husbandry, and even
      statistical analyses can all benefit animal welfare and scientific quality. If
      refinement is not actively sought, outdated and unnecessarily invasive techniques
      may not be replaced by better methods as they become available, and thus outdated
      information is passed down to the next generation, causing perpetuation of old
      fashioned methods. This leads to a spiral of ignorance, leading ultimately to
      poor practice, poor animal welfare and poor-quality scientific data. Refinement
      is a legal and ethical requirement, yet refinements may not always be
      implemented. There are numerous obstacles to the implementation of refinement,
      which may be real or perceived. Either way, in order to take refinement forward,
      it is important to coordinate the approach to refinement, validate the science
      behind refinement, ensure there is adequate education and training in new
      techniques, improve liaison between users and make sure there is feedback on
      suitability of refinements for use. Overall, refinement requires a coordinated
      ongoing process of critical appraisal of practice and active scrutiny of
      resources for likely improvements. In the busy world of biomedical research, this
      process needs help. In order to develop these themes further, a workshop was held
      at the LASA Winter Meeting 2006, UK, to assist in identifying potential obstacles
      to refinement, and then to explore and develop strategies for overcoming these
      obstacles in key areas. A range of strategies appropriate to different
      circumstances was identified, which should facilitate the implementation of
      refinements.

PMID- 18625584
TI  - Oral instillation with surfactant phospholipid: a reliable alternative to
      intratracheal injection in mouse studies.
AB  - The intratracheal (IT) injection technique has been widely used in the mouse
      studies of pulmonary diseases. Here, we describe a non-invasive technique using
      oral instillation challenge with the surfactant phospholipid that may
      advantageously replace the traditional IT technique. We performed comparative
      studies between oral instillation and IT injection of both vectors (adeno
      associated virus, AAV vector) and bacteria (Pseudomonas aeruginosa). Our results
      demonstrated that the oral instillation is a reliable alternative to IT
      injection. The administration of a fluorophore-labelled AAV vector demonstrated a
      similar pattern of distribution and quantity of vector delivered by oral
      instillation compared with IT injection. In addition, administration of AAV5
      alpha-1 antitrypsin (AAT) to the lungs by oral instillation resulted in similar
      levels of AAT in both the lung homogenates and sera compared with the IT
      injection group. In our study of P. aeruginosa delivery, oral instillation
      resulted in similar mouse weight loss, cytokine levels in the epithelial lining
      fluid [interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha, neutrophil
      chemokine and macrophage inflammatory protein-1alpha], lung histology/pathology
      and bacterial loads. Therefore, we conclude that oral instillation of materials
      mixed with surfactant phospholipid is an adequate and reproducible technique to
      replace the invasive IT injection procedure for the delivery of either vector or
      bacteria to the lungs. This procedure has the benefits of eliminating the
      discomfort, local inflammation and mortality associated with the more invasive IT
      surgical procedures.

PMID- 18625585
TI  - Continual measurement of intramedullary blood perfusion with laser Doppler
      flowmetry in intact and ostectomized tibiae of rabbits.
AB  - Blood flow is important for the healing of bone fractures. Until now, however,
      there have been no publications on the daily, continual measurement of
      intramedullary blood perfusion using laser Doppler flowmetry (LDF) in the
      conscious animal. In this study, a model for the daily, continual measurement of
      intramedullary blood perfusion by LDF and the temperature near the cortex both in
      intact and ostectomized tibiae in the conscious rabbit is described. The probes
      for blood perfusion and temperature measurement were implanted permanently at
      three different localizations into the right tibia of 10 adult New Zealand White
      rabbits. The probes were held in place by a bilateral, single-plane external
      fixator. In five of these animals, a midshaft tibial ostectomy was created in
      order to simulate a fracture. Intramedullary blood perfusion and temperature were
      measured daily over 49 days. While in intact tibiae no significant (P > 0.05)
      differences were found in blood perfusion readings taken at various time points,
      for mean values or for blood perfusion over time, in ostectomized tibiae the
      differences were significant: various time points (P = 0.0056), mean values (P =
      0.0034) and blood perfusion over time (P = 0.0337). Blood perfusion readings at
      the centre probe were elevated compared with those at the proximal and distal
      probes. Thus, a revascularization in the ostectomy gap during the fracture
      healing was proven by means of the LDF. No influence of the blood perfusion on
      the temperature in the ostectomy area could be determined during healing of the
      ostectomy. The described model seems suitable for the continual measurement of
      intramedullary blood perfusion both in intact and ostectomized tibiae in the
      conscious rabbit.

PMID- 18625586
TI  - Normative data of multifrequency tympanometry in rabbits.
AB  - In an experimental study, we evaluated acoustic immittance in rabbits in order to
      use these data as normative values for further experimental investigations. This
      study is the first experimental evaluation of both conventional 226 Hz and
      multifrequency tympanometry (MFT) in rabbits. For the investigation, we used 33
      female New Zealand rabbits weighing 3.2-4.4 kg and aged six months. Bilateral
      measurements using conventional 226 Hz and MFT were performed under general
      anaesthetic. A 226 Hz tympanogram was recorded for all animals by conducting an
      air pressure sweep from +200 to -400 daPa at a rate of 50 daPa/s. Subsequent
      tympanograms were recorded over a wide frequency range from 250 to 2000 Hz. The
      acoustic impedance device used in this study provided reproducible and evaluable
      tympanograms. The applied tone frequency of 226 Hz proved to be especially
      suitable for determining compliance. Normative data obtained from our study
      reveal the resonance frequency to be 1368 +/- 205 standard deviation (SD) for the
      right side and 1413 +/- 216 SD for the left side. The values for physiological
      acoustic immittance of the middle ear in the rabbit obtained here can serve as
      normative data in subsequent experimental animal studies.

PMID- 18625588
TI  - A novel method for transuterine identification of piglets.
AB  - Implantable microchips provide a secure, permanent and unique identification of
      individual animals. When performing fetal intervention studies in experimental
      animal models easy and secure identification of fetuses is desirable, as having
      test and control groups within the same uterus reduces the total number of
      animals used in a study. The aims of this study were: (1) to establish a protocol
      to identify porcine fetuses in utero by microchip implantation and (2) to assess
      postnatally whether clinical or pathological reactions to the implant occurred.
      Two Danish Landrace/Danish Large White crossbred sows at day 100 of gestation
      were used. The sows were sedated with azaperone and induced with propofol
      intravenously. Anaesthesia was maintained with isoflurane and oxygen. Antibiotics
      were administered intramuscularly (i.m.) at induction and analgesia was given pre
      , intra- and postoperatively. A laparotomy was performed and the uterus
      exteriorized. The rump of the first fetus was recognized through the uterine wall
      and the thigh muscle of the fetus was fixed between the thumb and the forefinger.
      The microchip was then implanted into the fetus at an angle of 45 degrees i.m. in
      the lateral hindleg using an insertion device with a 12G needle. The same
      procedure was done in every fetus. The uterus was returned to the abdomen and the
      abdominal wall closed. The sows gave birth to 24 liveborn piglets and one
      stillborn. None of the liveborn piglets were limping at the time of birth and no
      visible cutaneous or palpable reactions on the hindlegs were observed. Following
      euthanasia, the microchip was easily localized and no macroscopic reactions at
      the implantation site were seen. None of the piglets had more than one microchip
      implanted. Histology showed a chronic mild foreign body granulomatous
      inflammatory response with peripheral eosinophils surrounding the microchip. No
      inflammation was evident in the adjacent muscles. It is concluded that
      transuterine identification of piglets two weeks before delivery is feasible
      using a microchip implant as an effective, easy and reliable method for
      identification of individuals after birth.

PMID- 18625587
TI  - Persistent changes in arterial blood gases in fetal sheep.
AB  - Two anaesthetic protocols were compared using pregnant sheep. In both groups of
      animals, anaesthesia was induced using an intravenous (i.v.) injection of
      diazepam and ketamine. The ewes were then intubated for positive pressure
      ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8%
      halothane. If the ewe showed any signs of awakening, one of two protocols was
      followed. First, the halothane concentration was increased to 2-3% until the ewe
      was completely anaesthetized. Second, the halothane concentration was not
      altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1
      mg/kg) until again completely anaesthetized. At the completion of surgery,
      maternal recovery was rapid and similar between the two groups. However, five
      days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses
      receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were
      statistically significantly depressed when compared with the fetuses receiving
      additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL).
      These results led us to conclude that certain anaesthetic protocols, in spite of
      good maternal recovery, can lead to deleterious effects upon the fetus that
      persist for at least five days after surgery.

PMID- 18625589
TI  - The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in
      Beagle dogs.
AB  - The noble gas xenon seems to have minimal cardiovascular side-effects and so may
      be an ideal anaesthetic agent when investigating cardiovascular physiology. In
      comparison with standard modern anaesthetics, we investigated the haemodynamic
      and hormonal effects of xenon in Beagle dogs. After a 30 min baseline period,
      anaesthesia was induced with propofol and maintained with either (1) 1.2%
      isoflurane/70% nitrous oxide (N(2)O), (2) 0.8% isoflurane/0.5 microg/kg/min
      remifentanil or (3) 63% xenon/0.5 microg/kg/min remifentanil (n = 6 per group).
      Haemodynamics were recorded and blood samples taken before and 60 min after
      induction. Mean arterial blood pressure (MAP) was higher in conscious dogs than
      during isoflurane/N(2)O (86 +/- 2 vs. 65 +/- 2 mmHg, mean +/- SEM) and
      isoflurane/remifentanil anaesthesia (95 +/- 2 vs. 67 +/- 3 mmHg), whereas MAP did
      not decrease significantly in response to xenon/remifentanil anaesthesia (96 +/-
      4 vs. 85 +/- 6 mmHg). Bradycardia was present during isoflurane/remifentanil (54
      +/- 2/min) and xenon/remifentanil (40 +/- 3/min), but not during isoflurane/N(2)O
      anaesthesia (98 +/- 3/min, P < 0.05). Xenon/remifentanil anaesthesia induced the
      highest reduction in cardiac output (CO) (-61%), and the highest increase in
      systemic vascular resistance (+120%) among all treatment groups (P < 0.05). A
      simultaneous increase in endogenous adrenaline and noradrenaline concentrations
      could only be observed in the xenon/remifentanil group, whereas angiotensin II
      and vasopressin concentrations increased in all groups. In conclusion,
      xenon/remifentanil anaesthesia maintains MAP but reduces heart rate and CO and is
      associated with a considerable stimulation of vasopressor hormones in Beagle
      dogs. Therefore, xenon/remifentanil exerts a new quality of adverse haemodynamic
      effects different from volatile anaesthetics and may not perform better during
      studies of cardiovascular physiology.

PMID- 18625590
TI  - Experimental model of membranous nephropathy in mice: sequence of histological
      and biochemical events.
AB  - An experimental model of membranous nephropathy (MN) has not been established
      fully in mice. We characterized the time course of MN in a murine MN model
      induced by cationic bovine serum albumin (cBSA). Preimmunized mice received cBSA
      intravenously for six weeks to induce MN and were then sacrificed at different
      times. Metabolic profiles, renal histopathology, lymphocyte subsets, serum anti
      cBSA immunoglobulins (Igs), antibody subclasses and circulating immune complexes
      (CIC) were evaluated to study the severity and mechanisms of disease initiation
      and progression. Clinical symptoms of overt proteinuria, hypoalbuminaemia and
      hypercholesterolaemia were observed from week 4, and typical histological
      findings of diffuse thickening of the glomerular basement membrane and
      subepithelial deposition were identified after week 6. Granular fluorescent
      staining for IgG and complement C3 were observed as early as week 4. Total
      splenocyte number increased, but the percentages of CD4+ and CD8+ cells did not
      change as the disease progressed. The predominant isotype of anti-cBSA Igs was
      IgG1, suggesting a T-helper 2 cell-prone immune response in the development of
      MN. The strong positive immunofluorescent staining of the immune complex
      concomitant with higher concentrations of Igs in serum but no significant change
      in CIC levels before week 4 suggest the involvement of in situ deposition of
      immune complex in the process of MN. This murine model resembles the clinical and
      pathological features of human MN and may provide a tool for investigating MN;
      this model may also have potential applications in gene-knockout or transgenic
      mouse technologies.

PMID- 18625591
TI  - Immunoreactive vasoactive intestinal polypeptide and vasopressin cells after a
      protein malnutrition diet in the suprachiasmatic nucleus of the rat.
AB  - The aim of the present study was to evaluate the effects of prenatal and
      postnatal protein deprivation on the morphology and density of vasopressin (VP)
      and vasoactive intestinal polypeptide (VIP) immunoreactive neurons in the
      suprachiasmatic nucleus (SCN) of young rats. Female Wistar rats were fed either
      6% (malnourished group) or 25% (control group) casein diet five weeks before
      conception, during gestation and lactation. After weaning, the pups were
      maintained on the same diet until sacrificed at 30 days of age. The major and
      minor axes, somatic area and the density of VP- and VIP-immunoreactive neurons
      were evaluated in the middle sections of the SCN. The present study shows that
      chronic protein malnutrition (ChPM) in VP neurons induces a significant decrease
      in number of cells (-31%,) and a significant increase in major and minor axes and
      somatic area (+12.2%, +21.1% and +15.0%, respectively). The VIP cells showed a
      significant decrease in cellular density (-41.5%) and a significant increase in
      minor axis (+13.5%) and somatic area (+10.1%). Our findings suggest that ChPM
      induces abnormalities in the density and morphology of the soma of VP and VIP
      neurons. These alterations may be a morphological substrate underlying circadian
      alterations previously observed in malnourished rats.

PMID- 18625592
TI  - Klebsiella oxytoca: opportunistic infections in laboratory rodents.
AB  - Opportunistic pathogens have become increasingly relevant as the causative agents
      of clinical disease and pathological lesions in laboratory animals. This study
      was conducted to evaluate the role of Klebsiella oxytoca as an opportunistic
      pathogen in laboratory rodents. Therefore, K. oxytoca-induced lesions were
      studied from 2004 to early 2006 in naturally infected rodent colonies maintained
      at The Jackson Laboratory (TJL), Bar Harbor, USA, the Animal Research Centre
      (Tierforschungszentrum, TFZ) of the University of Ulm, Germany and the Central
      Animal Facility (ZTM) of the Hannover Medical School, Germany. K. oxytoca
      infections were observed in substrains of C3H/HeJ mice, which carry the Tlr4(Lps
      d) allele; in LEW.1AR1-iddm rats, the latter being prone to diabetes mellitus; in
      immunodeficient NMRI-Foxn1(nu) mice; and in mole voles, Ellobius lutescens. The
      main lesions observed were severe suppurative otitis media, urogenital tract
      infections and pneumonia. Bacteriological examination revealed K. oxytoca as
      monocultures in all cases. Clonality analysis performed on strains isolated at
      the ZTM and TFZ (serotyping, pulse field gel electrophoresis [PFGE],
      enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction,
      sequencing of 16S rRNA and rpoB genes) revealed that the majority of bacteria
      belonged to two clones, one in each facility, expressing the capsule type K55
      (ZTM) or K72 (TFZ). Two strains, one isolated at the ZTM and one at the TFZ,
      showed different PFGE and ERIC pattern than all other isolates and both expressed
      capsule type K35. In conclusion, K. oxytoca is an opportunistic pathogen capable
      of inducing pathological lesions in different rodent species.

PMID- 18625593
TI  - Detection of Corynebacterium kutscheri in the faeces of subclinically infected
      mice.
AB  - Mice were infected experimentally and subclinically with Corynebacterium
      kutscheri to recover the organism from mice faeces. The faeces were then cultured
      using selective furazolidone-nalidixic acid-colimycin agar. The number of C.
      kutscheri per gram of fresh faeces varied from mouse to mouse, but once
      established in the intestine, the organism was excreted in the faeces for at
      least five months. Viable bacteria were detected in most of the faecal samples,
      including those stored in the animal room for five days. The number of organisms
      in the stored faeces decreased gradually but did not differ significantly from
      those in the fresh faeces until they had been stored for more than three days.
      Many infected mice excreted between 10(4.77) and 10(5.37) colony forming units
      (CFU) of C. kutscheri per day in their faeces, and one mouse even excreted
      10(3.74) CFU at eight weeks postinfection. These values showed little daily
      variation. Our present study showed that subclinically infected mice discharged
      the organism continuously and persistently in their faeces. Therefore, faecal
      samples would be useful for monitoring infection with C. kutscheri in living mice
      in a manner that is not stressful for the animals.

PMID- 18625594
TI  - Unilateral optical nerve hypoplasia in a Beagle dog.
AB  - Unilateral (left eye) optic nerve hypoplasia was detected in a six-month-old male
      Beagle dog. Vision testing indicated that the left eye had poor vision and
      testing the pupillary light reflex showed the left eye to have an absence of the
      afferent pathway of the reflex but it had a normal efferent pathway.
      Ophthalmoscopy revealed a small-sized optic disc, winding retinal artery and
      dilated retinal vasculature in the left globe. Electroretinography showed no
      abnormal findings even in the left globe. Histopathologically, the left optic
      nerve was markedly hypoplastic and was composed of sparse neural elements and a
      moderate amount of connective and glial tissues. In the retina of the left globe,
      the nerve fibre layer and the ganglion cell layer were reduced in thickness,
      although a small number of ganglion cells were still present. There were no
      abnormal findings detected in the right globe and the right optic nerve. The
      brain appeared normal macroscopically.

PMID- 18625595
TI  - Chronic diarrhoea in a teenager.

PMID- 18625596
TI  - News feature: Costly US anticancer drugs pose problems for doctors and patients.

PMID- 18625597
TI  - NHS publishes survival rates for common operations for individual hospitals.

PMID- 18625598
TI  - A model based on age, sex, and morbidity to explain variation in UK general
      practice prescribing: cohort study.
AB  - OBJECTIVE: To examine whether patient level morbidity based measure of clinical
      case mix explains variations in prescribing in general practice. DESIGN:
      Retrospective study of a cohort of patients followed for one year. SETTING: UK
      General Practice Research Database. PARTICIPANTS: 129 general practices, with a
      total list size of 1 032 072. MAIN OUTCOME MEASURES: Each patient was assigned a
      morbidity group on the bases of diagnoses, age, and sex using the Johns Hopkins
      adjusted clinical group case mix system. Multilevel regression models were used
      to explain variability in prescribing, with age, sex, and morbidity as
      predictors. RESULTS: The median number of prescriptions issued annually to a
      patient is 2 (90% range 0 to 18). The number of prescriptions issued to a patient
      increases with age and morbidity. Age and sex explained only 10% of the total
      variation in prescribing compared with 80% after including morbidity. When
      variation in prescribing was split between practices and within practices, most
      of the variation was at the practice level. Morbidity explained both variations
      well. CONCLUSIONS: Inclusion of a diagnosis based patient morbidity measure in
      prescribing models can explain a large amount of variability, both between
      practices and within practices. The use of patient based case mix systems may
      prove useful in allocation of budgets and therefore should be investigated
      further when examining prescribing patterns in general practices in the UK,
      particularly for specific therapeutic areas.

PMID- 18625599
TI  - Critical issue is rapidity of review of new drugs.

PMID- 18625600
TI  - How the government is failing the health service.

PMID- 18625601
TI  - Clinical dashboards and open kimonos.

PMID- 18625602
TI  - Doctors' infantalisation.

PMID- 18625603
TI  - Why not adopt the blacklist of yore?

PMID- 18625604
TI  - A discriminating judgment.

PMID- 18625606
TI  - Prosecution over drug price fixing collapses.

PMID- 18625607
TI  - Debate on abortion is deferred until autumn.

PMID- 18625608
TI  - Report calls for better UK coordination to solve devolution problems.

PMID- 18625610
TI  - Arabidopsis transcriptome analysis under drought, cold, high-salinity and ABA
      treatment conditions using a tiling array.
AB  - Plants respond and adapt to drought, cold and high-salinity stresses in order to
      survive. In this study, we applied Arabidopsis Affymetrix tiling arrays to study
      the whole genome transcriptome under drought, cold, high-salinity and ABA
      treatment conditions. The bioinformatic analysis using the tiling array data
      showed that 7,719 non-AGI transcriptional units (TUs) exist in the unannotated
      "intergenic" regions of Arabidopsis genome. These include 1,275 and 181 TUs that
      are induced and downregulated, respectively, by the stress or ABA treatments.
      Most of the non-AGI TUs are hypothetical non-protein-coding RNAs. About 80% of
      the non-AGI TUs belong to pairs of the fully overlapping sense-antisense
      transcripts (fSATs). Significant linear correlation between the expression ratios
      (treated/untreated) of the sense TUs and the ratios of the antisense TUs was
      observed in the SATs of AGI code/non-AGI TU. We studied the biogenesis mechanisms
      of the stress- or ABA-inducible antisense RNAs and found that the expression of
      sense TUs is necessary for the stress- or ABA-inducible expression of the
      antisense TUs in the fSATs (AGI code/non-AGI TU).

PMID- 18625609
TI  - Genome barriers between nuclei and mitochondria exemplified by cytoplasmic male
      sterility.
AB  - Since plants retain genomes of an extremely large size in mitochondria (200-2,400
      kb), and mitochondrial protein complexes are comprised of chimeric structures of
      nuclear- and mitochondrial-encoded subunits, coordination of gene expression
      between the nuclei and mitochondria is indispensable for sound plant development.
      It has been well documented that the nucleus regulates organelle gene expression.
      This regulation is called anterograde regulation. On the other hand, recent
      studies have demonstrated that signals emitted from organelles regulate nuclear
      gene expression. This process is known as retrograde signaling. Incompatibility
      caused by genome barriers between a nucleus and foreign mitochondria destines the
      fate of pollen to be dead in cytoplasmic male sterility (CMS), and studies of CMS
      confirm that pollen fertility is associated with anterograde/retrograde
      signaling. This review summarizes the current perspectives in CMS and fertility
      restoration, mainly from the viewpoint of anterograde/retrograde signaling.

PMID- 18625611
TI  - Metagenomics reveals our incomplete knowledge of global diversity.

PMID- 18625612
TI  - Semantic reclassification of the UMLS concepts.
AB  - Accurate semantic classification is valuable for text mining and knowledge-based
      tasks that perform inference based on semantic classes. To benefit applications
      using the semantic classification of the Unified Medical Language System (UMLS)
      concepts, we automatically reclassified the concepts based on their lexical and
      contextual features. The new classification is useful for auditing the original
      UMLS semantic classification and for building biomedical text mining
      applications. AVAILABILITY:
      http://www.dbmi.columbia.edu/~juf7002/reclassify_production

PMID- 18625613
TI  - RNA secondary structure of the feline immunodeficiency virus 5'UTR and Gag coding
      region.
AB  - The 5' untranslated region (5'UTR) of lentiviral genomic RNA is highly
      structured, and is the site of multiple RNA-RNA and RNA-protein interactions
      throughout the viral life cycle. The 5'UTR plays a critical role during
      transcription, translational regulation, genome dimerization, reverse
      transcription priming and encapsidation. The 5'UTR structures of human
      lentiviruses have been extensively studied, yet the respective role and
      conformation of each domain is still controversial. To gain insight into the
      structure-function relationship of lentiviral 5'UTRs, we modelled the RNA
      structure of the feline immunodeficiency virus (FIV), a virus that is
      evolutionarily distant from the primate viruses. Through combined chemical and
      enzymatic structure probing and a thorough phylogenetic study, we establish a
      model for the secondary structure of the 5'UTR and Gag coding region. This work
      highlights properties common to all lentiviruses, like the primer binding site
      structure and the presence of a stable stem-loop at the 5' extremity. We find
      that FIV has also evolved specific features, including a long stem loop
      overlapping the end of the 5'UTR and the beginning of the coding region. In
      addition, we observed footprints of Gag protein on each side of the initiation
      codon, this sheds light on the role of the sequences required for encapsidation.

PMID- 18625614
TI  - Revealing unique properties of the ribosome using a network based analysis.
AB  - The ribosome is a complex molecular machine that offers many potential sites for
      functional interference, therefore representing a major target for antibacterial
      drugs. The growing number of high-resolution structures of ribosomes from
      different organisms, in free form and in complex with various ligands, provides
      unique data for structural and comparative analyses of RNA structures. We model
      the ribosome structure as a network, where nucleotides are represented as nodes
      and intermolecular interactions as edges. As shown previously for proteins, we
      found that the major functional sites of the ribosome exhibit significantly high
      centrality measures. Specifically, we demonstrate that mutations that strongly
      affect ribosome function and assembly can be distinguished from mild mutations
      based on their network properties. Furthermore, we observed that closeness
      centrality of the rRNA nucleotides is highly conserved in the bacteria,
      suggesting the network representation as a comparative tool for the ribosome
      analysis. Finally, we suggest a global topology perspective to characterize
      functional sites and to reveal the unique properties of the ribosome.

PMID- 18625615
TI  - Geographical variation of disease manifestations in systemic sclerosis: a report
      from the EULAR Scleroderma Trials and Research (EUSTAR) group database.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a vasculopathy with increased tissue
      deposition of collagen. The aetiology is unknown. Genetic and environmental
      susceptibility factors have been implicated. It is unknown whether disease
      presentation varies within Europe. AIMS AND METHODS: The baseline data of all SSc
      patients entered in the EULAR Scleroderma Trials and Research (EUSTAR) database
      up to April 2007 were analysed for geographical differences with regard to organ
      involvement, and geographical clusters with regard to clinical subsets (diffuse
      vs limited SSc) and autoantibodies (anticentromere vs anti-Scl70). RESULTS: 3661
      patients from 79 centres in 62 cities and 23 countries were analysed. There was
      no clear trend between geographical coordinates and SSc subsets, although there
      appeared to be an increased prevalence of Scl70 in the more eastern centres.
      There was no association between geographical longitude or latitude and the age
      at the onset of Raynaud's phenomenon or the onset of non-Raynaud's symptoms.
      There was also a trend for the more eastern centres to care for patients with a
      higher prevalence of more severe organ manifestations (pulmonary arterial
      hypertension, cardiac involvement). Between different centres within one city
      there was a large variability in the frequency of organ complications.
      CONCLUSION: This analysis suggests that eastern centres care for more severe SSc
      manifestations in Europe. Large differences in patient referral account for a
      large local variability of SSc presentations and preclude the identification of
      genetic or environmental factors.

PMID- 18625616
TI  - Evaluating guidelines on continuation of anti-tumour necrosis factor treatment
      after 3 months: clinical effectiveness and costs of observed care and different
      alternative strategies.
AB  - OBJECTIVE: To study the adherence of rheumatologists to the Dutch guidelines for
      anti-tumour necrosis factor alpha (TNF-alpha) treatment. The secondary objective
      was to evaluate alternatives to the present guidelines with regard to the
      percentage of responders and costs. METHODS: The response (>1.2 DAS28 decrease)
      in patients who started on anti-TNF-alpha treatment for the first time was
      evaluated at 3 and 6 months after initiation. How many patients continued or
      discontinued their initial anti-TNF-alpha treatment was evaluated. Possible
      alternative guidelines were evaluated by means of a decision tree, with regard to
      the expected percentage of successfully (responders) and unsuccessfully treated
      patients and expected costs. RESULTS: At 3 months 56% (N = 306) and 44% (N = 233)
      of all 539 evaluable patients were classified as responders or non-responders,
      respectively. Despite the guidelines, most (81%) (N = 189) of the non-responders
      continued treatment. 37% of the non-responders who continued anti-TNF-alpha
      treatment were eventually classified as responders at 6 months. Decision
      analytical modelling showed that with equal expected costs all alternative
      strategies would result in more responders than according to theoretical full
      adherence with the guidelines. "Continuation in case of partial response" had the
      best trade-off between successfully treated patients (64%) and unsuccessfully
      treated patients (17%). CONCLUSION: There was suboptimal adherence to the Dutch
      guidelines for treatment with anti-TNF-alpha for rheumatoid arthritis patients.
      This seemed to be justified by the fact that a delayed response up to 6 months
      was shown. If treatment is continued despite a non-response at 3 months, this is
      only recommended in patients with at least a partial response (at least 0.6 DAS28
      improvement).

PMID- 18625617
TI  - Bone marrow lesions predict increase in knee cartilage defects and loss of
      cartilage volume in middle-aged women without knee pain over 2 years.
AB  - OBJECTIVE: Bone marrow lesions (BML) are important in established knee
      osteoarthritis, predicting pain and progression of disease. Whether BML are also
      associated with longitudinal changes in knee structure in an asymptomatic
      population is unknown. METHODS: 148 healthy pain-free women in middle age with no
      history of knee injury or clinical knee osteoarthritis who had a magnetic
      resonance imaging (MRI) scan performed on their dominant knee at baseline, had
      another MRI 2 years later to assess whether having a BML present at baseline
      affected change in tibiofemoral cartilage defects and tibial cartilage volume.
      RESULTS: BML were present in 14.9% of women at baseline. The risk of progression
      of total tibiofemoral cartilage defects was significantly higher when a very
      large BML was present (odds ratio 5.55, 95% CI 1.04 to 29.6) compared with when
      no BML was present, after adjusting for potential confounders. In the lateral
      compartment, the rate of cartilage volume loss was significantly greater when a
      BML was present after adjusting for confounders (regression coefficient 39.2
      mm(3), 95% CI 11.1 to 67.2, p = 0.007). CONCLUSIONS: In healthy women without
      pain at baseline, large BML were associated with both progression of cartilage
      defects in the whole tibiofemoral joint and more rapid lateral tibial cartilage
      loss. These data suggest that the relationship between BML and knee cartilage in
      healthy women is similar to that described in established osteoarthritis. It is
      possible that BML may predict an increased risk of knee osteoarthritis and
      facilitate the identification of novel interventions to prevent disease.

PMID- 18625618
TI  - Development of an ASAS-endorsed disease activity score (ASDAS) in patients with
      ankylosing spondylitis.
AB  - OBJECTIVES: To develop a new index for disease activity in ankylosing spondylitis
      (ASDAS) that is truthful, discriminative and feasible, and includes domains/items
      that are considered relevant by patients and doctors. METHODS: Eleven candidate
      variables covering six domains of disease activity, selected by ASAS experts in a
      Delphi exercise, were tested in a three-step approach, similar to the methodology
      used for the disease activity score in rheumatoid arthritis. Data on 708 patients
      included in ISSAS (International Study on Starting tumour necrosis factor
      blocking agents in Ankylosing Spondylitis) were used. Cross validation was
      carried out in the OASIS cohort (Outcome in Ankylosing Spondylitis International
      Study). RESULTS: Principal component analysis disclosed three factors with
      eigenvalues >0.75: patient assessments, peripheral joint assessments and acute
      phase reactants. Discriminant function analysis resulted in a correct
      classification in approximately 72% of the cases (prior probability approximately
      50%). Regression analysis resulted in an index with five variables (total back
      pain, patient global assessment, duration of morning stiffness, C-reactive
      protein (CRP) and erythrocyte sedimentation rate (ESR)). Three additional
      candidate indices were designed using similar methodology while omitting either
      ESR or CRP or patient global assessment. All four scores correlated with the Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI; r = 0.67-0.80), patient
      (0.58-0.75) and physician's global assessment (0.41-0.48) of disease activity.
      All four candidate ASDAS indices performed better than BASDAI or single-item
      variables in discriminating between high and low disease activity state,
      according to doctors as well as patients in the OASIS cohort. CONCLUSION: The
      first steps in the development of a new assessment tool of disease activity in AS
      derived four candidate indices with good face and construct validity, and high
      discriminant capacity.

PMID- 18625619
TI  - Testing the druggable endothelial differentiation gene 2 knee osteoarthritis
      genetic factor for replication in a wide range of sample collections.
AB  - OBJECTIVES: To replicate a previously reported association with osteoarthritis
      (OA) of the promoter single nucleotide polymorphism (SNP) rs10980705 in the
      endothelial differentiation gene 2 (EDG2). METHODS: Five collections of samples,
      four from Europe and one from China, were studied. They included patients with 3
      OA phenotypes: 1501 with knee OA, 1497 with hip OA and 376 with generalised OA. A
      total of 2521 controls were also studied. Allele and genotype frequencies of the
      rs10980705 SNP were analysed in each individual sample collection and in pooled
      data. In addition, a meta-analysis to incorporate results from the original
      Japanese report was performed. RESULTS: The association of the rs10980705 SNP
      with knee OA was not replicated in any of the five sample collections studied or
      in their combined analysis (odds ratio (OR) 1.10, 95% CI 0.98 to 1.22; p = 0.10).
      Meta-analysis of all data, including the original Japanese study, did show
      association with knee OA (OR 1.15, 95% CI 1.06 to 1.26; p = 0.002) but the effect
      was accounted for by the Japanese data and was less significant than the original
      report. No association was found with hip OA or with generalised OA. CONCLUSIONS:
      The original report of a promising genetic association between a druggable G
      protein coupled receptor, EDG2, and knee OA has not been replicated. This lack of
      replication could be due to a modest effect of the promoter polymorphism that
      will require even larger studies (the winners curse) although a more pronounced
      effect in the Asian population vs Europeans cannot be excluded.

PMID- 18625620
TI  - Severe alterations in expression and localisation of {alpha}6{beta}4 integrin in
      salivary gland acini from patients with Sjogren syndrome.
AB  - OBJECTIVES: In salivary glands from patients with Sjogren syndrome,
      overexpression of laminins 1 and 5 and disorganisation of the acinar basal lamina
      have been reported. Laminin 5 mediates association of the basal lamina with
      epithelial cells by forming adhesion complexes upon interaction with alpha6beta4
      integrin. In the present work, mRNA and protein levels of alpha6beta4 integrin
      were determined and its localisation in salivary glands evaluated in patients
      with Sjogren syndrome. METHODS: Salivary glands of 12 patients with Sjogren
      syndrome and 8 controls were studied. The mRNA and protein levels of alpha6beta4
      were determined by semiquantitative reverse transcriptase (RT)-PCR and western
      blot analysis, respectively. The subcellular localisation of alpha6beta4 and
      laminin were evaluated by confocal microscopy. RESULTS: In patients, no
      significant differences in alpha6 and beta4 mRNA levels were detected. However,
      beta4 integrin protein levels were significantly lower, whereas, changes in
      alpha6, were highly variable. In controls, alpha6beta4 was detected in the
      basolateral and basal surface of serous and mucous acini, respectively. In
      patients, alterations in alpha6beta4 distribution were particularly dramatic for
      acini with strong basal lamina disorganisation. alpha6beta4 was also detected in
      the cytoplasm and lateral plasma membrane in serous and mucous acini. CONCLUSION:
      Mild alterations in the basal lamina correlated with lateral redistribution of
      alpha6beta4 integrin and the formation of new cell-cell adhesions that help
      maintain acinar organisation and promote cell survival. Conversely, in cases with
      severe basal lamina alterations, lateral alpha6beta4 redistribution was no longer
      sufficient to maintain acinar cell survival. Thus, maintenance of equilibrium
      between cell-cell and cell-basal lamina attachment is required to sustain gland
      cell survival.

PMID- 18625621
TI  - Exposure to nuclear antigens contributes to the induction of humoral autoimmunity
      during tumour necrosis factor alpha blockade.
AB  - OBJECTIVE: Type I interferons and apoptotic particles contribute to antinuclear
      autoimmunity in experimental models. This study assessed whether similar
      mechanisms contribute to break peripheral B-cell tolerance in humans by studying
      the induction of antinuclear antibodies by tumour necrosis factor blockade in
      spondyloarthritis. METHODS: 40 spondyloarthritis patients treated with infliximab
      or etanercept and 20 renal cell carcinoma patients treated with sorafenib were
      studied. Serum antinucleosome IgM and nucleosomes were measured by ELISA. Type I
      interferon serum activity was measured using a functional reporter cell assay.
      Synovial apoptosis was assessed by terminal transferase nick end-labelling
      (TUNEL) assay and anti-active caspase-3 immunostaining. Complement was measured
      by nephelometry. RESULTS: Despite a similar clinical improvement and reduction of
      synovial inflammation, antinucleosome IgM were induced by infliximab but not
      etanercept. This induction did not correlate with type I interferon activity,
      which was transiently downmodulated by infliximab but persistently upregulated by
      etanercept. In contrast, antinucleosome IgM levels did correlate with serum
      nucleosome levels, which were significantly upregulated by infliximab but not by
      etanercept treatment. This increase in serum nucleosome levels was not directly
      related to massive cell death, but rather to a decrease of complement 3 and 4
      serum levels during infliximab treatment. CONCLUSION: Infliximab and etanercept
      have a differential effect on both type I interferon activity and nucleosome
      levels. Only elevated serum nucleosomes relate to the induction of antinucleosome
      antibodies after infliximab treatment.

PMID- 18625623
TI  - Tumour-like mass lesion: an under-recognised presentation of primary angiitis of
      the central nervous system.
AB  - OBJECTIVE: To describe the occurrence of mass lesions (ML) in primary angiitis of
      the central nervous system (PACNS) and assess the utility of diagnostic testing
      and treatment. METHODS: We examined the case records of the Cleveland Clinic
      (CC), Massachusetts General Hospital (MGH), and the English language medical
      literature, for biopsy-proven PACNS cases presenting as a solitary ML. Relevant
      clinical variables were extracted and analysed with JMP software. RESULTS: We
      identified a total of 38 ML: eight of 202 (4.0%) patients with CC/MGH and 30 of
      535 (5.6%) patients with PACNS identified from the medical literature. A higher
      percentage (13 of 45; 29%) was seen in the amyloid-related angiitis subset.
      Poorer outcomes were reported in the amyloid group, with five deaths. Of the non
      amyloid group, better outcomes were seen in the group treated with
      corticosteroids and cyclophosphamide as compared with the group treated with
      corticosteroids alone. CONCLUSIONS: Although rare, PACNS should be considered in
      the differential diagnosis of ML; greater awareness of this manifestation may
      facilitate more prompt diagnosis and treatment. Biopsy evidence of angiitis is
      required for diagnosis; specimens should routinely be stained for amyloid. While
      excision of the lesion may be curative, aggressive immunosuppressive therapy is
      associated with favourable outcomes and may obviate the need for surgery.

PMID- 18625622
TI  - IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients
      with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals:
      results from a 24-week multicentre randomised placebo-controlled trial.
AB  - OBJECTIVES: The phase III RADIATE study examined the efficacy and safety of
      tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with
      rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist
      therapy. METHODS: 499 patients with inadequate response to one or more TNF
      antagonists were randomly assigned to receive 8 mg/kg or 4 mg/kg tocilizumab or
      placebo (control) intravenously every 4 weeks with stable methotrexate for 24
      weeks. ACR20 responses, secondary efficacy and safety endpoints were assessed.
      RESULTS: ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% of patients in
      the 8 mg/kg, 4 mg/kg and control groups, respectively (less than p<0.001 both
      tocilizumab groups versus control). At week 4 more patients achieved ACR20 in 8
      mg/kg tocilizumab versus controls (less than p = 0.001). Patients responded
      regardless of most recently failed anti-TNF or the number of failed treatments.
      DAS28 remission (DAS28 <2.6) rates at week 24 were clearly dose related, being
      achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups (less
      than p = 0.001 for 8 mg/kg and p = 0.053 for 4 mg/kg versus control). Most
      adverse events were mild or moderate with overall incidences of 84.0%, 87.1% and
      80.6%, respectively. The most common adverse events with higher incidence in
      tocilizumab groups were infections, gastrointestinal symptoms, rash and headache.
      The incidence of serious adverse events was higher in controls (11.3%) than in
      the 8 mg/kg (6.3%) and 4 mg/kg (7.4%) groups. CONCLUSION: Tocilizumab plus
      methotrexate is effective in achieving rapid and sustained improvements in signs
      and symptoms of RA in patients with inadequate response to TNF antagonists and
      has a manageable safety profile. TRIAL REGISTRATION NUMBER: NCT00106522.

PMID- 18625624
TI  - Evidence for a distinctive pattern of bone formation in enthesophytes.
AB  - OBJECTIVES: The mechanism of new bone formation at entheses in spondyloarthritis
      (SpA) is poorly understood, but it is a key factor contributing to disability in
      disease. As bony spur development is also an age-related phenomenon, spurs in
      elderly dissecting room cadavers were studied in order to establish general
      principles relating to their development. METHODS: Spurs of different sizes were
      studied by routine histology at 26 different entheses (a total of 76 specimens)
      from the upper limb, lower limb and spine. The percentage of bone:marrow was
      compared in the posterior part of the calcaneus in cadavers with and without
      Achilles spurs to ascertain the relationship between spurs and immediately
      adjacent trabecular bone. RESULTS: Bony spur formation was a common age related
      phenomena and typically occurred in the most fibrous part of an enthesis.
      Paradoxically, it was often heralded by the initial appearance of a thick zone of
      calcified fibrocartilage that subsequently developed bony nodules within it.
      Uncalcified fibrocartilage was more prominent around large spurs. Endochondral,
      intramembranous and chondroidal ossification all contributed to spur formation
      and growth, but cell hypertrophy and florid vascular invasion of a cellular
      calcified cartilage, typical of endochondral ossification, were not conspicuous
      features. CONCLUSION: Entheseal new bone formation occurs by a combination of
      three methods of ossification. However, endochondral ossification was atypical
      and differed from that seen in the normal development of cartilage bones or
      during fracture healing. How the inflammatory process modulates these processes
      could lead to a better understanding of entheseal new bone formation in SpA.

PMID- 18625625
TI  - Wegener's granulomatosis patients show an adequate antibody response to influenza
      vaccination.
AB  - OBJECTIVES: Wegener's granulomatosis (WG) is a systemic vasculitis characterised
      by relapsing and remitting disease activity. Immunosuppressive drugs are used to
      control disease, but increase susceptibility to infection. Therefore, influenza
      vaccination should be considered in WG patients. This study was performed to
      assess the immunogenicity of influenza vaccination in WG patients. METHODS: A
      randomised, controlled trial was performed in WG patients with quiescent disease,
      defined as a Birmingham vasculitis activity score (BVAS) less than 2. Patients
      were randomly assigned to receive influenza vaccination (n = 49) or to
      participate as controls (n = 23). In addition, healthy controls (n = 49) were
      vaccinated. At entry and at 1 and 3-4 months after entry, antibody responses to
      vaccination were determined. Furthermore, disease activity was measured (BVAS),
      adverse effects were recorded and antineutrophil cytoplasmic autoantibody (ANCA)
      titres were determined. RESULTS: WG patients achieved high seroprotection rates
      to all three influenza strains, comparable with healthy controls. Only the A/H1N1
      strain patients had a lower seroconversion rate (p = 0.002) and geometric mean
      titre (p = 0.037) than controls. After 1 month, one control and one vaccinated WG
      patient had developed active disease. At 3-4 months, two additional control
      patients had developed active disease compared with none of the vaccinated
      patients (p = 0.099). Vaccination did not influence ANCA titres. Adverse effects
      did not differ between patients and healthy controls. CONCLUSIONS: Influenza
      vaccination in WG patients with quiescent disease induced a sufficient antibody
      response. TRIAL REGISTRATION NUMBER: NTR1130.

PMID- 18625626
TI  - Vitamin K in hand osteoarthritis: results from a randomised clinical trial.
AB  - OBJECTIVES: Vitamin K has bone and cartilage effects, and previously shown to be
      associated with radiographic osteoarthritis. We evaluated vitamin K's effect on
      hand osteoarthritis in a randomised controlled trial. METHODS: This was an
      ancillary study to a randomised controlled trial assessing the effects of
      phylloquinone supplementation (vitamin K arm) versus placebo on bone loss and
      vascular calcification among older adults regardless of their vitamin K status.
      At the final 3-year study visit, we assessed the effects of vitamin K versus
      placebo on hand x-ray features of osteoarthritis using logistic regression and
      intention to treat, and also restricted analysis to the subgroup that had
      insufficient vitamin K concentrations at baseline. RESULTS: This ancillary study
      had 378 participants (193 in vitamin K arm, 185 in placebo arm). There were no
      effects of randomisation to vitamin K for radiographic osteoarthritis outcomes.
      Those with insufficient vitamin K at baseline who attained sufficient
      concentrations at follow-up had trends towards 47% less joint space narrowing (p
      = 0.02). CONCLUSIONS: There was no overall effect of vitamin K on radiographic
      hand osteoarthritis. SUBJECTS: that were insufficient in vitamin K at baseline
      who attained sufficient concentrations at follow-up may have had a benefit in
      joint space narrowing. A clinical trial in those who are vitamin K insufficient
      may be warranted. TRIAL REGISTRATION NUMBER: NCT00183001.

PMID- 18625628
TI  - Responsiveness of the International Classification of Functioning, Disability and
      Health (ICF) Core Set for rheumatoid arthritis.
AB  - BACKGROUND: The comprehensive International Classification of Functioning,
      Disability and Health (ICF) Core Set for rheumatoid arthritis (RA) is a selection
      of 96 categories from the ICF, representing relevant aspects in the functioning
      of patients with RA. OBJECTIVES: To study the responsiveness of the ICF Core Set
      for RA in rheumatological practice. METHODS: A total of 46 patients with RA (72%
      women, mean (SD) age 53.6 (12.6) years, disease duration 6.3 (8.0) years) were
      interviewed at baseline and again after 6 months treatment with a disease
      modifying antirheumatic drug (DMARD), applying the ICF Core Set for RA with
      qualifiers for problems on a modified three-point scale (no problem,
      mild/moderate, severe/complete). Patient-reported outcomes included Modified
      Health Assessment Questionnaire (MHAQ) and Short-Form 36 (SF-36) health survey,
      and disease activity was calculated. Responsiveness was measured as change in
      qualifiers in ICF categories, and was also compared with change in patient
      reported outcomes. RESULTS: After 6 months of DMARD treatment, improvement by at
      least one qualifier was seen in 20% of patients (averaged across all ICF
      categories), 71% experienced no change and 9% experienced worsening symptoms.
      Findings were similar across the different aspects of functioning. Mainly
      moderate effect sizes were seen for 6-month changes in the ICF Core Set for RA,
      especially in patients with improved health status, with similar effect size for
      disease activity. The components in the ICF Core Set for RA were only weakly
      associated with patient-reported outcomes and disease activity. CONCLUSIONS: The
      ICF Core Set for RA demonstrated moderate responsiveness in this real-life
      setting of patients where minor changes occurred during treatment with DMARDs.

PMID- 18625627
TI  - Disease progression in mothers of children enrolled in the Research Registry for
      Neonatal Lupus.
AB  - OBJECTIVE: To evaluate autoimmune disease progression in asymptomatic and pauci
      symptomatic mothers of children with neonatal lupus (NL). METHODS: Clinical
      information on mothers enrolled in the Research Registry for NL (RRNL) was
      obtained from medical records. Genotyping was performed for -308A/G tumour
      necrosis factor (TNF)alpha, 869T/C transforming growth factor (TGF)beta and 
      889C/T interleukin (IL)1alpha. RESULTS: Of the 321 mothers enrolled, 229 had at
      least 6 months of follow-up. Of the 51 mothers who were asymptomatic at the NL
      child's birth, 26 progressed: 12 developed pauci-undifferentiated autoimmune
      syndrome (pauci-UAS), 2 poly-UAS, 7 SS, 4 SLE and 1 SLE/SS. The median time to
      develop any symptom was 3.15 years. Of the 37 mothers classified as pauci-UAS at
      the NL child's birth, 16 progressed: 5 developed poly-UAS, 6 Sjogren syndrome
      (SS), 4 systemic lupus erythematosus (SLE) and 1 SLE/SS. Of the pauci-UAS mothers
      enrolled within 1 year, the median time to progression was 6.7 years. Four
      mothers developed lupus nephritis (two asymptomatic, two pauci-UAS). The
      probability of an asymptomatic mother developing SLE by 10 years was 18.6%, and
      developing probable/definite SS was 27.9%. NL manifestations did not predict
      disease progression in an asymptomatic mother. Mothers with anti-Sjogren syndrome
      A antigen (SSA/)Ro and anti-Sjogren syndrome B antigen (SSB)/La were nearly twice
      as likely to develop an autoimmune disease as mothers with anti-SSA/Ro only. Only
      TGFbetaT/T was significantly higher in SLE mothers compared to asymptomatic
      mothers (p = 0.03). CONCLUSIONS: Continued follow-up of asymptomatic NL mothers
      is warranted since nearly half progress, albeit few develop SLE. While the anti
      SSB/La antibodies may be a risk factor for progression, further work is needed to
      determine reliable biomarkers in otherwise healthy women with anti-SSA/Ro
      antibodies identified solely because of an NL child.

PMID- 18625629
TI  - Tight control and intensified COBRA combination treatment in early rheumatoid
      arthritis: 90% remission in a pilot trial.
AB  - OBJECTIVE: To investigate the efficacy and feasibility of an intensive
      combination treatment in early rheumatoid arthritis (RA) combined with monitoring
      both disease activity and cartilage degradation. METHODS: In a pilot trial, 21
      patients with active early RA (mean DAS28 5.3; mean disease duration 3 months)
      were treated with COBRA treatment comprising sulfasalazine, methotrexate and high
      dose step-down prednisolone, intensified by adding hydroxychloroquine and
      continued low-dose prednisolone. In addition, based on measurements of disease
      activity or a marker of cartilage degradation (CTX-II), treatment adjustments
      were possible with methotrexate intensification after 8 or 21 weeks; and with
      infliximab after 21 weeks. RESULTS: Nineteen of 21 patients (90%) were in
      remission (DAS28 <2.6) after 40 weeks (8 weeks, 57%; 21 weeks, 76%). American
      College of Rheumatology (ACR) criteria, ACR20, 50, 70 and 90 improvements rates
      were 100%, 95%, 71% and 43% respectively. CTX-II excretion decreased by mean (SD)
      347(292) ng/mmol creatinine, but only 50% of patients reduced their CTX-II
      excretion below the cut-off point. The two monitoring groups showed no
      significant difference in remission according to DAS score or CTX-II excretion,
      despite a trend towards more intensive treatment in the CTX-II group. Treatment
      intensification was feasible according to protocol. CONCLUSIONS: This small pilot
      study suggests that intensified and tightly controlled COBRA treatment is
      uniquely effective in early RA. TRIAL REGISTRATION NUMBER: ISRCTN96372677.

PMID- 18625630
TI  - Complement activation in patients with primary antiphospholipid syndrome.
AB  - OBJECTIVE: To investigate the significance of complement activation in patients
      with primary antiphospholipid syndrome (APS). METHODS: Thirty-six patients with
      primary APS, 42 control patients with non-systemic lupus erythematosus (SLE)
      connective tissue diseases, and 36 healthy volunteers were analysed
      retrospectively. Serum complement levels (C3, C4, CH(50)) and anaphylatoxins
      (C3a, C4a, C5a) were examined in all subjects, and serum complement regulatory
      factors (factor H and factor I) were measured in patients with primary APS.
      Plasma anticoagulant activity was determined in a mixing test using the activated
      partial thromboplastin time. RESULTS: Serum complement levels were significantly
      lower in patients with primary APS than in patients with non-SLE connective
      tissue diseases (mean (SD) C3: 81.07 (17.86) vs 109.80 (22.76) mg/dl, p<0.001;
      C4: 13.04 (8.49) vs 21.70 (6.96) mg/dl, p<0.001; CH(50): 31.32 (8.76) vs 41.40
      (7.70) U/ml, p<0.001) or healthy volunteers. Only two healthy subjects with low
      serum C4 levels showed hypocomplementaemia, whereas most patients with primary
      APS showed raised serum C3a and C4a. No subjects showed raised C5a. Patients with
      primary APS with low serum C3 or C4 had significantly higher levels of C3a or C4a
      than healthy controls. No patients had low serum complement regulatory factors.
      Among patients with primary APS, hypocomplementaemia was significantly more
      common in those with high anticoagulant activity than in those with low or normal
      activity. CONCLUSION: Hypocomplementaemia is common in patients with primary APS,
      reflecting complement activation and consumption, and was correlated with
      anticoagulant activity, suggesting that antiphospholipid antibodies may activate
      monocytes and macrophages via anaphylatoxins produced in complement activation.

PMID- 18625631
TI  - Pedometer counts superior to physical activity scale for identifying health
      markers in older adults.
AB  - OBJECTIVE: Measuring physical activity is a key part of studying its health
      effects. Questionnaires and pedometers each have weaknesses but are the cheapest
      and easiest to use measurement methods for large-scale studies. We examined their
      capacity to detect expected associations between physical activity and a range of
      surrogate health measures. DESIGN: Cross-sectional analysis of 669 community
      dwelling participants (mean age 63.3 (7.7) years) who completed the Physical
      Activity Scale for the Elderly (PASE) questionnaire and who, within 2 weeks, wore
      a pedometer for 7 days. RESULTS: PASE score and step count were only poorly
      correlated (r = 0.37 in women, r = 0.30 in men). Of 12 expected associations
      examined between activity and surrogate markers of health, 10 were detected as
      statistically significant by step counts but only 3 by PASE scores. Significant
      associations in the expected direction were found between step counts and high
      density lipoprotein, body mass index, waist circumference, waist-to-hip ratio,
      blood glucose level, white cell count and fibrinogen. There was no association
      with either systolic or diastolic blood pressure. The association between PASE
      score and these markers was detected as significant only for body mass index and
      waist circumference in women and waist-to-hip ratio in both sexes. Associations
      were stronger for steps multiplied by stride length than for raw step count.
      CONCLUSIONS: Pedometer-derived step counts are a more valid measurement of
      overall physical activity in this sample than PASE score. Researchers should use
      objective measures of physical activity whenever possible.

PMID- 18625632
TI  - Is BAFF the murderer in lupus?

PMID- 18625633
TI  - Mycophenolate mofetil in the treatment of lupus nephritis--7 years on.

PMID- 18625634
TI  - A prospective multicentre study of mycophenolate mofetil combined with
      prednisolone as induction therapy in 213 patients with active lupus nephritis.
AB  - Mycophenolate mofetil (MMF) with prednisolone has been associated with high
      remission rates when used as induction treatment for lupus nephritis. This
      prospective, multicentre, cohort study investigates the efficacy and safety of
      this regimen over 24 weeks in 213 Chinese patients with active lupus nephritis
      (Classes III, IV, V or combination). Baseline activity index (AI) was 6.91+/-3.33
      and chronicity index (CI) was 1.9+/-1.2. The remission rate was 82.6% at 24 weeks
      (complete remission, 34.3%; partial remission, 48.4%). There were significant
      (P<0.01) improvements in kidney function shown by reductions in proteinuria,
      serum albumin, serum creatinine and creatinine clearance, as well as in systemic
      lupus erythematosus disease activity index (SLEDAI) scores. Independent risk
      factors influencing remission were pathological classification (including Class V
      and III or Class V and IV nephritis) and elevated serum creatinine at baseline
      (OR 2.967, 95% CI: 1.479-6.332, P=0.001 and OR 1.007, 95% CI: 1.002-1.011,
      P=0.001, respectively). Patients with concomitant membranous features on biopsy
      had a lower remission rate than those with Class III and IV nephritis (66.7% vs
      87.3%, P=0.002). Renal biopsy was repeated in 25 patients following treatment.
      There was a transition to less severe pathological morphologies in majority of
      subjects. Infections were monitored throughout treatment: eight patients (3.8%)
      experienced bacterial infections, whereas herpes zoster occurred in seven
      patients. Nine patients (4.2%) suffered from gastrointestinal upset, which
      resolved without discontinuation of MMF. One patient became leucopenic, whereas
      another died from active disease unrelated to kidney symptoms. MMF combined with
      prednisolone is an effective and well-tolerated induction treatment for patients
      with active lupus nephritis and for controlling SLE systemic activity.

PMID- 18625635
TI  - CD8+CD28-, suppressive T cells in systemic lupus erythematosus.
AB  - Recent studies show that a CD8+CD28- phenotype of T-cell population inhibits the
      reactivity of T-helper cells either by a contact-dependent mechanism or with
      secreting suppressive cytokines. In this study, we have explored the peripheral
      blood CD8+CD28- T-cell population in 53 patients with systemic lupus
      erythematosus (SLE) in comparison to healthy and diseased control groups. The
      distribution of CD28- cells within CD8+ population has been found significantly
      lower in patients with SLE than in healthy individuals. While there were no
      significant differences in the expression of costimulatory molecules CD80 and
      CD86, the CD40 expression on monocytes was found significantly lower and there
      was a slight decrease of expression of Interleukin-10 (IL-10) in CD8+CD28-
      population in patients with SLE. The Transforming growth factor-beta (TGF-beta)
      mRNA expression was found higher in CD8+CD28- T cells. Neither activation induced
      nor time-dependent change in the frequency of CD8+CD28- cells has been observed
      following stimulation at various time-points indicating that the control of CD28
      expression was not dependent on the presence of sustained stimulations. Decrease
      in CD8+CD28- T cells which normally produce TGF-beta and their low-level IL-10
      content may reflect impaired T-cell suppression and accordingly, increased T cell
      help to autoreactive B cells in patients with SLE.

PMID- 18625636
TI  - Induction treatment of proliferative lupus nephritis with leflunomide combined
      with prednisone: a prospective multi-centre observational study.
AB  - To evaluate the efficacy and safety of leflunomide in the treatment of
      proliferative lupus nephritis, a prospective multi-centre observational study was
      conducted. Patients with biopsy proven proliferative lupus nephritis were
      assigned to receive either leflunomide or cyclophosphamide with concomitant
      prednisone. Leflunomide was given orally with a loading dose of 1 mg/kg/day for 3
      days followed by 30 mg/day. Intravenous cyclophosphamide was administered monthly
      at a dose of 0.5 g/m2 of body-surface area. A total of 110 patients were
      enrolled, 70 in the leflunomide group and 40 in the cyclophosphamide group. The
      complete remission rate in the leflunomide group was 21% and partial remission
      rate 52%, as compared with 18% and 55%, respectively, in the cyclophosphamide
      group. Renal parameters and systemic lupus erythematosus disease activity index
      improved significantly and similarly in both groups. Serum creatinine decreased
      or stabilized in both treatment groups. No significant difference was noted with
      respect to clinical outcome between groups. Repeat biopsy also showed a
      significant reduction of active lesions in kidney pathology after 6 months of
      leflunomide treatment. Major adverse events, similar in both treatment groups,
      included infection, alopecia and hypertension. Leflunomide, compared with
      cyclophosphamide, in combination with prednisone was effective in the induction
      therapy of proliferative lupus nephritis and was generally well-tolerated.

PMID- 18625637
TI  - Defects in Notch1 upregulation upon activation of T Cells from patients with
      systemic lupus erythematosus are related to lupus disease activity.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the
      production of autoantibodies and deposition of immune complexes in various
      organs. T cells play a central role in driving disease progression, and multiple
      defects in T cells from patients with SLE have been uncovered. Notch signalling
      is an evolutionarily well-conserved signalling cascade involved in the
      proliferation, differentiation and apoptosis of T lymphocytes during development
      and peripheral effector functions. In this study, we investigated the correlation
      between expression of Notch receptor and the severity of SLE disease. On the
      contrary to T lymphocytes from healthy controls (n=11), Tlymphocytes from
      patients with active SLE (n=12) failed to upregulate Notch1 upon in-vitro
      stimulation as quantified by quantitative real time RT-PCR (P<or=0.025). Among
      patients with inactive SLE (n=10), those with late onset of flare exhibited
      significantly less Notch1 upregulation compared with SLE patients with remission.
      Expression of the Notch target genes, Hes1 and deltex, was also lower in patients
      with active SLE. The decrease in Notch1 mRNA expression was consistent with less
      Notch1 protein expression in patients with active SLE. The defects in Notch1
      upregulation correlated with decreased proliferation, CD25 and Foxp3 expression
      upon stimulation in vitro. Taken together, the failure of T cells to upregulate
      Notch1 upon activation may be a key feature of active SLE and a potential
      therapeutic target.

PMID- 18625638
TI  - Systemic lupus erythematosus patients have increased number of circulating
      plasmacytoid dendritic cells, but decreased myeloid dendritic cells with
      deficient CD83 expression.
AB  - Dendritic cells (DCs) are functionally abnormal in systemic lupus erythematosus
      (SLE). However, previous studies have involved in-vitro cytokine-induced DCs. In
      this investigation, directly isolated circulating plasmacytoid DCs (pDCs) and
      myeloid DCs (mDCs) in SLE were studied. Blood dendritic cell antigen (BDCA)-4 and
      BDCA-1 magnetic isolation kits were used to isolate blood pDCs and mDCs from 30
      SLE patients and 36 controls. Their number and surface markers, and their
      relationship with lupus disease activity were evaluated. The percentage of pDCs
      per peripheral blood mononuclear cells was higher in SLE (0.33+/-0.14) than in
      controls (0.16+/-0.09, P<0.01), but that of mDCs was lower in SLE (0.43+/-0.14)
      than in controls (0.63+/-0.32; P<0.01). In controls, both pDCs and mDCs expressed
      high levels of MHC-II, however, the expression of CD86, CD83 and CCR7 on pDCs
      were significantly lower than that on mDCs (all P<0.05). mDCs from patients with
      SLE, particularly those with active disease, expressed lower CD83 than controls.
      In health, circulating mDCs may be more efficient than pDCs in stimulating T
      cells. In SLE, the increased number of circulating pDCs supports a pathogenic
      role for these cells, and the decreased mDC number and CD83 expression may
      explain the susceptibility to infections in these patients.

PMID- 18625639
TI  - Systemic lupus erythematosus and familial Mediterranean fever: a possible
      negative association between the two disease entities--report of four cases and
      review of the literature.
AB  - Serositis is a common clinical manifestation of systemic lupus erythematosus
      (SLE), as well as being the hallmark of familial Mediterranean fever (FMF), the
      most prevalent monogenic disease in the Jewish population. We have treated four
      patients who suffered from both SLE and FMF since 2001 in our clinic, which also
      serves as the national center for FMF. Our cases illustrate both similarities and
      dissimilarities between the clinical manifestations of these two diseases, an
      aspect which should be borne in mind, especially in the young female patients. In
      general, it seems that co-occurrence of FMF moderates the presentation of lupus.

PMID- 18625640
TI  - Kidney transplantation in lupus patients: a case-control study from a single
      centre.
AB  - This study was conducted to determine kidney transplantation (KTx) outcomes for
      Greek patients with renal failure caused by lupus nephritis (LN) compared with
      matched controls, kidney recipients with other causes of end-stage renal disease
      (ESRD). Twenty-six patients with systemic lupus erythematosus (SLE) subjected to
      26 kidney transplants were studied. For comparative purposes a case-control group
      was selected, matched for gender, source of donor, age and time of KTx. Patient
      and graft survival estimates were calculated with the Kaplan-Meier product limit
      estimator and survival estimates were compared with the log-rank test. All
      patients received cyclosporine or tacrolimus in combination with azathioprine or
      mycophenolate mofetil for chronic immunosuppression in addition to steroids.
      Fourteen transplants were from living-related donors and 12 were from deceased
      donors. The graft survival rates for lupus patients were 88% at 1 year, 67% at 5
      years, 38% at 10 years, poorer than the control survival rates of 92%, 92% and
      84% (P=0.004). Patient survival in the lupus group did not differ from that of
      the controls. Survival in the lupus group was 92% at 1 year, 77% at 5 years and
      77% at 10 years vs. 96%, 92% and 92% (P=0.26). Chronic allograft nephropathy was
      the major cause of graft loss. Recurrent LN was detected in two patients, but
      only one lead to graft failure. SLE patients compared with controls had
      significantly higher rates of hypertension, cardiovascular disease, infections
      and malignancies. Compared with matched controls, SLE patients had inferior but
      still satisfactory graft survival rates, whereas patient survival rates were
      similar.

PMID- 18625641
TI  - Adalimumab-induced lupus erythematosus.
AB  - Adalimumab, an anti-tumour necrosis factor agent, especially used in the
      treatment of rheumatoid arthritis, has a good safety profile. One of the most
      common side-effects of adalimumab is the development of autoantibodies. Despite
      the induction of autoantibodies, the clinical presentation of immune-mediated
      complications upon adalimumab therapy, including a lupus-like syndrome, is very
      rare. We have recently evaluated a new case of adalimumab-induced lupus
      erythematosus.

PMID- 18625642
TI  - Moyamoya syndrome associated with systemic lupus erythematosus.
AB  - Moyamoya disease is a rare, progressive cerebrovascular disorder that is
      characterized by a stenosis or occlusion of the bilateral internal carotid
      arteries and the development of collateral vessels. Transient ischemic attacks or
      seizures are the usual presentation of moyamoya disease in children, whereas
      cerebral hemorrhage is the most common symptom in adults. We report an 18-year
      old female patient with active lupus nephritis who presented with the sudden
      onset of left hemiparesis. Brain magnetic resonance imaging showed acute
      infarctions in the right basal ganglia and subcortical white matter of the right
      frontal lobe. Cerebral angiography showed the stenosis of the bilateral internal
      carotid arteries with rich basal collateral vessels (moyamoya vessels). There was
      no evidence of atherosclerosis or antiphospholipid syndrome. Glucocorticoid
      therapy was used to control the systemic lupus erythematosus. Prophylactic bypass
      surgery was performed to prevent recurrent ischemic attacks. This case report
      shows that an underlying cerebrovascular lesion of moyamoya vessels in a patient
      with systemic lupus erythematosus is susceptible to cerebrovascular accidents.

PMID- 18625643
TI  - Childhood systemic lupus erythematosus in Sultanate of Oman: demographics and
      clinical analysis.
AB  - There is a worldwide variation in the incidence of childhood manifestation of
      systemic lupus erythematosus, which may be related to environmental, genetic and
      geographical factors. The aim of the study is to describe for the first time the
      clinical and immunological characteristics of childhood onset systemic lupus
      erythematosus at diagnosis in the Sultanate of Oman. We retrospectively reviewed
      the records of 50 children with systemic lupus erythematosus fulfilling the
      American College of Rheumatology criteria between 1990 and 2006. There were 42
      girls and eight boys. The mean age of disease onset was low at 8.6 years (SD
      3.1). The female:male ratio was 5.3:1. The most frequent clinical manifestations
      at initial diagnosis were: articular (76%), cutaneous (70%), haematological (68%)
      and renal (64%) dominated by class IV nephritis, pulmonary (26%),
      neuropsychiatric (18%) and cardiac (10%). A positive antinuclear antibody (>1:80)
      was present in 94% at diagnosis. Positive anti-double stranded DNA was present in
      82% and low complement levels were present in 84% at diagnosis. This is the first
      review of childhood onset systemic lupus erythematosus in the Sultanate of Oman.

PMID- 18625644
TI  - Renal outcome and evolution of disease activity in Chinese lupus patients after
      renal transplantation.
AB  - Lupus nephritis constitutes the major cause of morbidity and mortality in SLE.
      The long-term outcome of renal transplantation in lupus patients remains
      controversial, and the recurrence of lupus activity is a major concern. This
      study aims to determine the long-term outcome of renal transplantation in Chinese
      lupus patients and the evolution of lupus activity. A total of 23 lupus patients
      undergoing renal transplantation were enrolled and compared with 94 matched
      controls. The overall patient and graft survival rates at 10 years post
      transplant in lupus group were not different from the control group (95.2% and
      57.7% vs. 90.7% and 66.3%). Recurrence of lupus nephritis in renal allograft and
      flare-ups of lupus activity were not observed in this study. The SLE group had
      less acute rejection than the control group (20.4% vs. 29.8%, P<0.05). The
      infection rate between the two groups was similar (39.1% vs. 51.1%, P=0.427),
      although SLE group had a significantly higher rate of developing avascular
      necrosis (17.4% vs. 2.1%, P=0.04). In conclusion, patient and graft survival
      rates and other major complications in Chinese lupus patients are comparable to
      non-lupus transplant recipients caused by other diseases. Chinese patients with
      SLE are suitable candidates for renal transplantation.

PMID- 18625645
TI  - Acute pancreatitis as initial manifestation of systemic lupus erythematosus and
      subacute cutaneous lupus erythematosus: report of two cases.

PMID- 18625646
TI  - Photoprotection: does it work?

PMID- 18625647
TI  - Oral contraceptives in systemic lupus erythematosus: the case for (and against).

PMID- 18625648
TI  - Childhood agricultural and adult occupational exposures to organic dusts in a
      population-based case-control study of systemic lupus erythematosus.
AB  - Organic dust exposure can influence the development and symptoms of immune
      related diseases such as atopy and asthma, but has rarely been examined in
      relation to systemic autoimmunity. The present analyses explore the association
      of lifetime farm and occupational organic dust exposures with systemic lupus
      erythematosus (SLE) in recently diagnosed patients (n = 265) compared with
      controls (n = 355) frequency matched by age, sex and state. Questionnaire data
      included childhood farm residence, childhood and adult experience with specific
      crops, and adult work in textiles, hog or poultry processing and paper or
      furniture manufacture. Adjusted odds ratios (OR) and 95% confidence intervals
      (CI) were estimated by logistic regression models including age, sex, state,
      race, education and silica exposure. Overall childhood or adult farm contact and
      childhood farm residence were not associated with SLE. Farm contact with
      livestock was inversely associated with SLE (OR = 0.55, 95% CI 0.35, 0.88). This
      effect was most pronounced among those with childhood farm residence and both
      childhood and adult livestock exposure (OR = 0.19; 95% CI 0.06, 0.63), but was
      difficult to separate from adult exposure to grains or corn. Other adult
      occupational exposures were not associated with SLE risk overall, regardless of
      childhood farm residence or livestock exposure, although an inverse association
      was seen among non-smokers (OR = 0.59; 95% CI 0.33, 1.1), particularly for
      textile work (OR = 0.34; 95% CI 0.19, 0.64). These exploratory findings support
      the development of studies to specifically investigate the effects of organic
      dust exposure on SLE risk, with particular attention to exposure assessment and
      characterization of demographics, smoking and other occupational exposures.

PMID- 18625649
TI  - Circulating thrombomodulin and vascular cell adhesion molecule-1 and renal
      vascular lesion in patients with lupus nephritis.
AB  - Currently, the detection of renal vascular lesions (VLS) in lupus nephritis (LN)
      mainly depends on biopsy examination, and lack surrogate biomarkers for clinical
      dynamic evaluation. The aim of the present study is to explore the correlation
      between circulatory endothelial damage biomarkers and VLS. Soluble E-selectin,
      thrombomodulin (TM) and vascular cell adhesion molecule-1 (VCAM-1) were measured
      by ELISA. TM and VCAM-1 levels both were significantly elevated in LN with VLS
      than in LN without VLS (P < 0.01). However, the serum E-selectin was not
      significantly changed in LN patients with and without VLS. A positive correlation
      was found between TM and serum creatinine (r = 0.617, P < 0.05) in patients with
      vascular lesions. In order to further analyse the relationship between TM level
      and severity degree of vascular lesions in LN patients, we subdivided the
      patients with vascular lesions into two groups: with thrombotic microangiopathy
      (TMA) and without TMA. TM level of the patients with TMA is significantly higher
      than those without TMA (P < 0.01). In conclusion, combined with renal
      pathological examination, monitoring the circulatory levels of TM and VCAM-1, can
      provide circulating biomarkers of VLS in LN patients.

PMID- 18625650
TI  - Prevalence and clinical associations of anti-Ku antibodies in systemic autoimmune
      diseases.
AB  - We retrospectively analysed the prevalence and clinical features associated to
      anti-Ku antibodies in patients affected by different autoimmune diseases. Anti-Ku
      antibodies are detected in 147 sera out of 7239 anti-ENA positive sera (2%). They
      are found in 2% of patients with systemic sclerosis (SSc) (8 out of 379), 1.8% of
      systemic lupus erythematosus (SLE) (7 out of 372) and 1.8% of undifferentiated
      connective tissue disease (UCTD) (9 out of 496) and more rarely in Sjogren
      Syndrome and rheumatoid arthritis. Most of anti-Ku positive patients were
      affected by UCTD and overlap syndromes, including polymyositis, SSc and SLE.
      Interstitial lung disease, myositis, articular symptoms, Raynaud's phenomenon and
      sicca represents the main clinical features detected in our cohort. The rate and
      severity of pulmonary disease is similar to those found in other SSc patients.
      Isolated anti-Ku were detected in about 47% of sera. No clinical differences were
      observed between these patients and subjects with multiple anti-nuclear
      specificities. However, anti-Ku are usually detected in association with other
      serological markers in SLE and Sjogren Syndrome, while they occurred isolated in
      SSc and polymyositis.

PMID- 18625651
TI  - Genetic susceptibility and haplotype analysis between Fcgamma receptor IIB and
      IIIA gene with systemic lupus erythematosus in Chinese population.
AB  - The objective of this study is to understand the role of FcgammaRIIB and
      FcgammaRIIIA gene in susceptibility to systemic lupus erythematosus (SLE), and to
      examine possible susceptible haplotypes between two genes. A total of 119
      patients with SLE from 95 nuclear families, aged from 14 to 78 years, were
      selected according to 1997 criteria of American College of Rheumatology. In
      addition, 316 family members of these patients were also genotyped. A family
      based association study was used to explore the relationship between gene
      polymorphism and SLE. We studied 13 single-nucleotide polymorphisms (SNPs)
      encoding non-synonymous substitution in the FcgammaRIIB and FcgammaRIIIA gene
      (four SNPs in the FcgammaRIIB gene and nine SNPs in the FcgammaRIIIA gene) with
      respect to genetic susceptibility to SLE. All SNPs were genotyped by restriction
      fragment length polymorphism method. Among 13 SNPs, univariate (single-marker)
      family-based association tests showed that variant alleles at only four SNPs
      (rs10917661 and rs1050501, in exon 2 and exon 5 of FcgammaRIIB gene, rs403016 and
      rs428888, in exon3 of FcgammaRIIIA gene respectively) were significantly
      associated with genetic susceptibility to SLE. Furthermore, the haplotype
      specific FBATs showed 50Ter-225Thr (34.1%, in FcgammaRIIB gene) and 72Arg-118Asn
      (40%, in the FcgammaRIIIA gene) haplotype were more frequently transmitted in SLE
      than other haplotypes (Z = 3.539, P = 0.00042; Z = 2.678, P = 0.007412
      respectively). But haplotypes were not found between FcgammaRIIB and FcgammaRIIIA
      gene Our results suggest that there were meaningful haplotype in FcgammaRIIIA and
      FcgammaRIIB gene respectively. FcgammaRIIIA and FcgammaRIIB genes in the
      pathogenesis of SLE may play an independent role in Chinese population.

PMID- 18625653
TI  - Efficacy of enteric-coated mycophenolate sodium in patients with resistant-type
      lupus nephritis: a prospective study.
AB  - The role of mycophenolate mofetil (MMF) is still controversial in the treatment
      of cyclophosphamide-resistant proliferative lupus nephritis (PLN). Enteric-coated
      mycophenolate sodium (EC-MPS) has less gastrointestinal adverse effects than MMF
      and is, therefore, increasingly utilised in organ transplantation. The aim of
      this study was to compare the efficacy and safety of EC-MPS versus an extended
      course of intravenous cyclophosphamide (ED-IVCY) in resistant-type PLN. Thirty
      one, biopsy-proven PLN, patients who failed to respond to an induction of IVCY
      were enrolled in a prospective, open-labelled, historically controlled study.
      Patients received 6 month of EC-MPS (720 mg b.i.d.) treatment. The patients in
      the ED-IVCY group, collected from a database, received a repeated 6-month course
      of monthly IVCY 0.5-1 g/m(2) of body surface area. Both groups received 0.5-1
      mg/kg/day of prednisolone. Primary outcomes were partial or complete responses. A
      repeated kidney biopsy was performed to evaluate the histological response. No
      serious adverse events or patient deaths were observed during the study. Both
      groups had comparable baseline characteristics. At 6 months, the EC-MPS group had
      a comparable response rate with the ED-IVCY group. There were significantly less
      adverse events in the EC-MPS group. Repeated biopsies showed significant
      improvement in the EC-MPS group. EC-MPS provides salutary efficacy and safety in
      the treatment of resistant-type PLN and can be a suitably alternative treatment
      to ED-IVCY.

PMID- 18625652
TI  - Haemolytic anaemia in a multi-ethnic cohort of lupus patients: a clinical and
      serological perspective.
AB  - Systemic lupus erythematosus is a chronic autoimmune disease that can be
      associated with a variety of haematological manifestations. We identified 76
      patients with haemolytic anaemia in a cohort of 1251 unrelated female lupus
      patients enrolled in our studies. The presence of the various American College of
      Rheumatology clinical criteria for lupus and serological specificities were
      determined in lupus patients with haemolytic anaemia and compared with a group of
      race-matched control lupus patients without haemolytic anaemia. Clinical data
      were obtained from medical records, and serological specificities were determined
      in our clinical immunology laboratory at OMRF. The presence of haemolytic anaemia
      in lupus patients was associated with a higher frequency of proteinuria (OR =
      2.70, P = 0.000031), urinary cellular casts (OR = 2.83, P = 0.000062), seizures
      (OR = 2.96, P = 0.00024), pericarditis (OR = 2.21, P = 0.0019), pleuritis (OR =
      1.72, P = 0.028) and lymphopenia (OR = 1.79, P = 0.015). These findings were
      independent of the presence of thrombocytopenia, which was approximately five
      times more common in lupus patients with haemolytic anaemia. Lupus patients with
      haemolytic anaemia were about 8 years younger than lupus patients without
      haemolytic anaemia at the time of disease onset (P = 0.000001). In the absence of
      thrombocytopenia, lupus patients with haemolytic anaemia were approximately two
      times more likely to have anti-dsDNA antibodies (P = 0.024). The presence of
      haemolytic anaemia is associated with a subset of lupus characterized by a
      younger age of disease onset, and a more severe disease with a higher likelihood
      of renal involvement, seizures, serositis and other cytopenias.

PMID- 18625654
TI  - Possible familial Mediterranean fever in a Caucasian patient with systemic lupus
      erythematosus.
AB  - We report the case of a Caucasian man with systemic lupus erythematosus who had
      recurrent fevers and abdominal pain. He was later found to carry E148Q
      polymorphism of MEFV, the gene responsible for familial Mediterranean fever.

PMID- 18625655
TI  - Rituximab treatment of pulmonary arterial hypertension associated with systemic
      lupus erythematosus: a case report.
AB  - Pulmonary hypertension is a common but underdiagnosed complication of systemic
      lupus erythematosus, which can be associated with significant morbidity and early
      mortality. Although often associated with anti-phospholipid antibodies, the
      etiology remains poorly understood. In case reports and small open trials, the
      anti-CD20, B-cell targeted therapeutic antibody, rituximab, has been reported to
      provide benefits for systemic lupus erythematosus patients with
      glomerulonephritis, anti-phospholipid antibody syndrome, vasculitis, arthritis,
      and refractory skin disease. However, the outcome of rituximab treatment of
      pulmonary arterial hypertension associated with systemic lupus erythematosus has
      not been described. We, therefore, present a case of a young systemic lupus
      erythematosus patient with early onset of pulmonary arterial hypertension during
      the disease course, refractory to multiple treatment modalities, who had
      significant improvement with rituximab therapy.

PMID- 18625656
TI  - Successful treatment of life-threatening Evans syndrome due to antiphospholipid
      antibody syndrome by rituximab-based regimen: a case with long-term follow-up.
AB  - An association of antiphospholipid antibody syndrome with antibodies directed
      against either phospholipids or plasma proteins strongly suggest that B-cell
      dysfunction may be involved in its pathogenesis. Antiphospholipid antibody
      syndrome with autoimmune cytopenias shows a poor response rate to conventional
      treatment with anticoagulants, glucocorticosteroids, immunosuppressive agents,
      intravenous immunoglobulin or plasmapheresis. We report a case of life
      threatening antiphospholipid antibody syndrome with Evans syndrome receiving
      successful multimodal treatment including anti-CD20 monoclonal antibody rituximab
      with long-term follow-up.

PMID- 18625657
TI  - Factors influencing adherence to medications in a group of patients with systemic
      lupus erythematosus in Jamaica.
AB  - The objective of this study was to examine the factors influencing adherence to
      medications in a group of patients with systemic lupus erythematosus (SLE) in
      Jamaica. A qualitative study was designed using a screening questionnaire and
      semi-structured interviews. The study was conducted in the rheumatology clinic at
      the University Hospital of the West Indies, Kingston, Jamaica. 75 patients with
      SLE including 20 interviewees, who had SLE for at least 1 year participated in
      the study. The main outcome measures were: (i) level of self-reported adherence
      in a sample of the clinic attendees and (ii) interviewees explanations of the
      reasons for taking or not taking drugs as prescribed by their physician. 56% of
      the 75 study participants reported taking their medications more than 85% of the
      time. High cost and poor availability of medications were the main reasons for
      poor adherence, but some patients chose not to take their medications because of
      side effects, perceived mild severity of their disease and/or a preference to
      take drugs only when symptomatic. Patients used herbal medicines to counteract
      side effects of Western medicines, to 'purge the blood' and to manage lupus
      symptoms when they had no medications. Religious beliefs were used as a coping
      strategy. Traditional use of herbal medicines is common particularly in patients
      from rural Jamaica, and may explain the observed use of herbal medicines in those
      who have emigrated to developed countries. Socio-economic constraints and poor
      drug availability are particularly important influences on poor adherence in
      Jamaican patients with SLE. Religious beliefs and use of herbal remedies do not
      seem to affect adherence adversely but are used when drugs cannot be obtained.

PMID- 18625658
TI  - Some concerns about the Sydney criteria for antiphospholipid syndrome.

PMID- 18625659
TI  - Prognosis of large-vessel giant cell arteritis.
AB  - OBJECTIVE: The prognosis of large-vessel GCA (LV-GCA) has not yet been
      investigated. How does it compare to GCA without arm vasculitis (GCA controls)?
      METHODS: Charts of 53 LV-GCA patients and 53 GCA controls were reviewed following
      a predetermined protocol. Telephone interviews of patients or their primary care
      physicians were conducted. Forty LV-GCA patients underwent follow-up duplex
      ultrasound examinations of proximal arm arteries. RESULTS: The mean observation
      time was 50 (s.d. +/- 31) months. None of the LV-GCA patients developed ischaemic
      arm complications. In 30%, proximal arm artery wall swelling disappeared
      completely. It decreased in 53%. In 8% it remained unchanged, in 5% it increased
      and in 5% arteries occluded with collateral flow. After the start of treatment,
      anterior ischaemic optic neuropathy developed neither in LV-GCA patients nor in
      GCA controls, amaurosis fugax occurred in 4 and 6%, arterial hypertension in 53
      and 66%, strokes in 9 and 9%, myocardial infarction in 2 and 2%, diabetes
      mellitus in 30 and 25%, osteoporosis in 38 and 23%, and osteoporotic fractures in
      15 and 4%, respectively. Mean corticosteroid dose was 3.7 mg/day. Mean duration
      of therapy was 42 months. All differences were insignificant. Four LV-GCA
      patients developed vasculitic popliteal artery stenoses. CONCLUSIONS: The
      prognosis of LV-GCA is benign with regard to ischaemic complications. Proximal
      artery wall swelling decreases in most cases. Its course is similar to GCA
      without proximal arm arteritis.

PMID- 18625660
TI  - Management of hypogammaglobulinaemia occurring in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is typically associated with
      hypergammaglobulinaemia but has been described in the setting of
      hypogammaglobulinaemia as well. The purpose of this article is to describe
      various cases of SLE and hypogammaglobulinaemia, review the literature and
      present management strategies for hypogammaglobulinaemia in SLE. METHODS: We
      describe five patients with SLE and antibody deficiency, and review the
      literature exploring the relationship between the two. RESULTS: Various types of
      antibody deficiency syndromes, including common variable immunodeficiency (CVID),
      IgA deficiency, IgM deficiency, drug-induced hypogammaglobulinaemia and
      hypogammaglobulinaemia secondary to nephrotic syndrome can occur in SLE. Antibody
      deficiency states can be treated with antibiotics and replacement immunoglobulin
      therapy (particularly CVID) but sometimes close monitoring is all that is
      required. CONCLUSION: Measurement of immunoglobulin levels is useful in SLE to
      identify coexisting antibody deficiency and the later development of
      hypogammaglobulinaemia. This allows monitoring and appropriate treatment to be
      instituted.

PMID- 18625661
TI  - An embarrassment of pain perceptions? Towards an understanding of and explanation
      for the clinical presentation of CRPS type 1.
AB  - Complex regional pain syndrome (CRPS), a fairly common problem in rheumatological
      and orthopaedic practice, is an allodynic pain state of uncertain pathology often
      variably and unpredictably responsive to treatments. Although published
      diagnostic criteria are available, in the reality of clinical practice these do
      not appear to encompass the wide variety of symptoms that a patient may present
      with. This leads to scepticism on the part of the clinician and confusion for the
      sufferer. This article aims to provide some explanations for an often bewildering
      clinical picture. We provide a construct for the plethora of symptoms that we
      have entitled 'the embarrassment of pain perceptions'. With the aid of a case
      report we examine recent research that suggests how peripherally based symptoms
      and signs arise from changes within the central nervous system, with particular
      attention given to the control function of the motor-proprioceptive integrative
      system. We speculate how these changes within the central nervous system may
      provide the patient with CRPS the ability to access complex layers of lower level
      perceptions that are normally suppressed. We propose that such a system may
      explain some of the clinical puzzlements seen in this condition and suggest that
      the complexities of CRPS may provide an insight into brain development through
      evolution, which is a fruitful area for interdisciplinary clinical and scientific
      research.

PMID- 18625662
TI  - Calcium-containing phosphate binders in dialysis patients with cardiovascular
      calcifications: should we CARE-2 avoid them?

PMID- 18625663
TI  - Maternal smoking during pregnancy, other prenatal and perinatal factors, and the
      risk of Legg-Calve-Perthes disease.
AB  - OBJECTIVE: The causes of Legg-Calve-Perthes disease are largely unknown, but this
      pediatric disease seems to result from interruption of the blood supply to the
      proximal femur and is considered a vascular disease. Because maternal smoking
      during pregnancy influences fetal development and is associated with
      cardiovascular diseases in offspring, we hypothesized that this exposure is a
      risk for Legg-Calve-Perthes disease and also investigated other markers of
      impaired fetal development and early-life exposures. MATERIALS AND METHODS: The
      Swedish Inpatient Register identified 852 individuals with a diagnosis of Legg
      Calve-Perthes disease from 1983 to 2005, individually matched by year of birth,
      age, sex, and region of residence with 4432 randomly selected control subjects.
      Linkage with the Swedish Medical Birth Register provided information on prenatal
      factors, including maternal smoking. Conditional logistic regression examined
      associations of maternal smoking during pregnancy and the other measures with the
      risk of Legg-Calve-Perthes disease in offspring, adjusted for socioeconomic index
      and other potential confounding factors. RESULTS: Maternal smoking during
      pregnancy was associated with an increased Legg-Calve-Perthes disease risk, and
      heavy smoking was associated with a risk increase of almost 100%. Very low birth
      weight and cesarean section were independently associated with approximately 240%
      and 36% increases in the risk of Legg-Calve-Perthes disease, respectively.
      CONCLUSION: Maternal smoking during pregnancy and other factors indicated by
      impaired fetal development may be associated with an increased risk of Legg-Calve
      Perthes disease.

PMID- 18625664
TI  - A prospective, cross-sectional survey study of the natural history of Niemann
      Pick disease type B.
AB  - OBJECTIVE: The objective of this study was to characterize the clinical features
      of patients with Niemann-Pick disease type B and to identify efficacy end points
      for future clinical trials of enzyme-replacement therapy. METHODS: Fifty-nine
      patients who had Niemann-Pick disease type B, were at least 6 years of age, and
      manifested at least 2 disease symptoms participated in this multicenter,
      multinational, cross-sectional survey study. Medical histories; physical
      examinations; assessments of cardiorespiratory function, clinical laboratory
      data, and liver and spleen volumes; radiographic evaluation of the lungs and bone
      age; and quality-of-life assessments were obtained during a 2- to 3-day period.
      RESULTS: Fifty-three percent of the patients were male, 92% were white, and the
      median age was 17.6 years. The R608del mutation accounted for 25% of all disease
      alleles. Most patients initially presented with splenomegaly (78%) or
      hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary
      infections and shortness of breath (42% each), and joint/limb pain (39%). Growth
      was markedly delayed during adolescence. Patients commonly had low levels of
      platelets and high-density lipoprotein, elevated levels of low-density
      lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte
      sphingomyelin, and serum chitotriosidase, and abnormal liver function test
      results. Nearly all patients had documented splenomegaly and hepatomegaly and
      interstitial lung disease. Patients commonly showed restrictive lung disease
      physiology with impaired pulmonary gas exchange and decreased maximal exercise
      tolerance. Quality of life was only mildly decreased by standardized
      questionnaires. The degree of splenomegaly correlated with most aspects of
      disease, including hepatomegaly, growth, lipid profile, hematologic parameters,
      and pulmonary function. CONCLUSIONS: This study documents the multisystem
      involvement and clinical variability of Niemann-Pick B disease. Several efficacy
      end points were identified for future clinical treatment studies. Because of its
      correlation with disease severity, spleen volume may be a useful surrogate end
      point in treatment trials, whereas biomarkers such as chitotriosidase also may
      play a role in monitoring patient treatment responses.

PMID- 18625665
TI  - Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome
      in childhood.
AB  - OBJECTIVE: The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No.
      606232) is a neurodevelopmental disorder that includes hypotonia, severely
      impaired development of speech and language, autistic-like behavior, and minor
      dysmorphic features. Although the number of reported cases is increasing, the
      22q13.3 deletion remains underdiagnosed because of failure in recognizing the
      clinical phenotype and detecting the 22qter deletion by routine chromosome
      analyses. Our goal is to contribute to the description of the neurobehavioral
      phenotype and brain abnormalities of this microdeletional syndrome. METHODS: We
      assessed neuromotor, sensory, language, communication, and social development and
      performed cerebral MRI and study of regional cerebral blood flow measured by
      positron emission tomography in 8 children carrying the 22q13.3 deletion.
      RESULTS: Despite variability in expression and severity, the children shared a
      common developmental profile characterized by hypotonia, sleep disorders, and
      poor response to their environment in early infancy; expressive language deficit
      contrasting with emergence of social reciprocity from ages approximately 3 to 5
      years; sensory processing dysfunction; and neuromotor disorders. Brain MRI
      findings were normal or showed a thin or morphologically atypical corpus
      callosum. Positron emission tomography study detected a localized dysfunction of
      the left temporal polar lobe and amygdala hypoperfusion. CONCLUSIONS: The
      developmental course of the 22q13.3 deletion syndrome belongs to pervasive
      developmental disorders but is distinct from autism. An improved description of
      the natural history of this syndrome should help in recognizing this largely
      underdiagnosed condition.

PMID- 18625666
TI  - Effects of continuous positive airway pressure on cardiovascular risk profile in
      patients with severe obstructive sleep apnea and metabolic syndrome.
AB  - BACKGROUND: The increased risk of atherosclerotic morbidity and mortality in
      patients with obstructive sleep apnea (OSA) has been linked to arterial
      hypertension, insulin resistance, systemic inflammation, and oxidative stress. We
      aimed to determine the effects of 8 weeks of therapy with continuous positive
      airway pressure (CPAP) on glucose and lipid profile, systemic inflammation,
      oxidative stress, and global cardiovascular disease (CVD) risk in patients with
      severe OSA and metabolic syndrome. METHODS: In 32 patients, serum cholesterol,
      triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A
      I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6,
      tumor necrosis factor (TNF)-alpha, leptin, malondialdehyde (MDA), and
      erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and
      after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment
      [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was
      calculated using the multivariable risk factor algorithm. RESULTS: In patients
      who used CPAP for > or = 4 h/night (n = 16), CPAP therapy reduced systolic BP and
      diastolic BP (p = 0.001 and p = 0.006, respectively), total cholesterol (p =
      0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF-alpha (p
      = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association
      with reductions in the global CVD risk (from 18.8 +/- 9.8 to 13.9 +/- 9.7%, p =
      0.001). No significant changes were seen in patients who used CPAP for < 4
      h/night. Mask leak was the strongest predictor of compliance with CPAP therapy.
      CONCLUSIONS: In patients with severe OSA and metabolic syndrome, good compliance
      to CPAP may improve insulin sensitivity, reduce systemic inflammation and
      oxidative stress, and reduce the global CVD risk.

PMID- 18625667
TI  - Distance and oxygen desaturation during the 6-min walk test as predictors of long
      term mortality in patients with COPD.
AB  - RATIONALE: The distance walked in the 6-min walk test (6MWT) predicts mortality
      in patients with severe COPD. Little is known about its prognostic value in
      patients with a wider range of COPD severity, living in different countries, and
      the potential additional impact of oxygen desaturation measured during the test.
      METHODS: We enrolled 576 stable COPD outpatients in Spain and the United States
      and observed them for at least 3 years (median, 60 months). We measured FEV1,
      body mass index, Pao2, Charlson comorbidity score, 6-min walk distance (6MWD),
      and oxygen saturation by pulse oximetry (Spo2) during the 6MWT. Desaturation was
      defined as a fall in Spo2 > or = 4% or Spo2 < 90%. Regression analysis helped
      determine the association between these variables and all-cause and respiratory
      mortality. RESULTS: The 6MWD was a good predictor of all-cause and respiratory
      mortality primarily in patients with FEV1 < 50% of predicted (p < 0.001) after
      adjusting for all covariates. Patients with desaturation during the 6MWT had a
      higher mortality rate than patients without desaturation (67% vs 38%, p < 0.001).
      Oxygen desaturation predicted mortality (relative risk, 2.63; 95% confidence
      interval, 1.53 to 4.51; p < 0.001) but with less power than Pao2 at rest.
      CONCLUSIONS: The 6MWD helps predict mortality primarily in patients with severe
      COPD. Although the oxygen desaturation profile during the 6MWT improves the
      predictive ability of the 6MWD, it appears to be of less relevance than in other
      lung diseases and than the resting Pao2.

PMID- 18625668
TI  - Assessment of regional progression of pulmonary emphysema with CT densitometry.
AB  - BACKGROUND: Lung densitometry is an effective method to assess overall
      progression of emphysema, but generally the location of the progression is not
      estimated. We hypothesized that progression of emphysema is the result of
      extension from affected areas toward less affected areas in the lung. To test
      this hypothesis, a method was developed to assess emphysema severity at different
      levels in the lungs in order to estimate regional changes. METHODS: Fifty
      subjects with emphysema due to alpha(1)-antitrypsin deficiency (AATD) [AATD
      deficiency of phenotype PiZZ (PiZ) group] and 16 subjects with general emphysema
      (general emphysema without phenotype PiZZ [non-PiZ] group) were scanned with CT
      at baseline and after 30 months. Densitometry was performed in 12 axial
      partitions of equal volumes. To indicate predominant location, craniocaudal
      locality was defined as the slope in the plot of densities against partitions.
      Regional progression of emphysema was calculated after volume correction, and its
      slope identifies the area of predominant progression. The hypothesis was tested
      by investigating the correlation between predominant location and predominant
      progression. RESULTS: As expected, the PiZ patients showed more basal emphysema
      than the non-PiZ group (craniocaudal locality, - 40.0 g/L vs - 6.2 g/L). Overall
      progression rate in PiZ patients was lower than in non-PiZ subjects. A
      significant correlation was found between craniocaudal locality and progression
      slope in PiZ subjects (R = 0.566, p < 0.001). In the non-PiZ group, no
      correlation was found. CONCLUSIONS: In the PiZ group, the more emphysema is
      distributed basally, the more progression was found in the basal area. This
      finding suggests that emphysema due to AATD spreads out from affected areas.

PMID- 18625669
TI  - Sleep quality and health-related quality of life in idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disorder
      resulting in irreversible scarring of the lung parenchyma. Although fatigue is a
      prominent symptom for patients with IPF, little is known about sleep quality in
      patients with IPF. METHODS: In this cross-sectional study of 41 patients with IPF
      from a prospectively designed cohort, we ascertained sleep quality by means of
      the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale.
      Health status, baseline demographics, and physiologic parameters were also
      assessed. RESULTS: Patients with IPF reported extremely poor sleep quality and
      high frequency of daytime sleepiness, which differs significantly from normal
      control populations. Further, poor sleep quality was not associated with body
      mass index, age, gender, or lung function. This population also demonstrated
      extremely poor health status in a number of domains, including physical function
      and vitality. Poor sleep quality (by the global PSQI) was significantly
      associated with decreased quality of life (QOL) in several domains, including
      role of physical function (r = - 0.58, p = 0.001), vitality (r = - 0.43, p =
      0.015), and role of emotions (r = - 0.40, p = 0.023). CONCLUSIONS: Poor sleep
      quality is extremely common in patients with IPF and is not predicted by
      variables traditionally associated with sleep-disordered breathing. Further, poor
      sleep quality is associated with poor QOL. These findings suggest that systematic
      evaluation of the cause of poor sleep quality in IPF is merited.

PMID- 18625670
TI  - Differences in the response to methacholine between the tidal breathing and
      dosimeter methods: influence of the dose of bronchoconstrictor agent delivered to
      the mouth.
AB  - BACKGROUND: It has been postulated that differences in provocative concentration
      of methacholine causing a 20% fall in FEV1 (PC20) values between the dosimeter
      method and tidal breathing method might be due to differences in the dose of
      agonist delivered to the mouth. The aim of the present study was to determine the
      influence of the dose of aerosol delivered to the mouth on differences in the
      response obtained with each challenge method. METHODS: This study measured airway
      responsiveness to methacholine by dosimeter method and tidal breathing method in
      27 subjects with suspected asthma. The dosimeter was modified to deliver an
      identical volume to that obtained with the tidal breathing method. Concentration
      response curves were characterized by the PC20. RESULTS: The dosimeter method
      PC20 was significantly higher than the tidal breathing method PC20, with
      geometric mean values of 4.03 (95% confidence interval [CI], 1.86 to 8.78 mg/mL)
      and 2.19 (95% CI, 1.32 to 3.64 mg/mL; p = 0.04), respectively. The mean
      difference in the PC20 value detected with each method was similar in subjects
      with tidal breathing method PC20 values > or = 2 mg/mL (0.77 doubling
      concentrations) and in those with PC20 values < 2 mg/mL (0.96 doubling
      concentrations; p = 0.83). CONCLUSIONS: The tidal breathing method produces PC20
      values significantly lower than a modified dosimeter method, which delivers the
      same volume of aerosol. These results suggest that the discordant PC20 values
      obtained with the two methods are not due to differences in the dose of agonist
      delivered to the mouth.

PMID- 18625671
TI  - The association between alcohol consumption and risk of COPD exacerbation in a
      veteran population.
AB  - BACKGROUND: Alcohol has been associated with COPD-related mortality but has not
      yet been demonstrated to be an independent risk factor for COPD exacerbation. Our
      objective was to evaluate the association between alcohol consumption and the
      subsequent risk of COPD exacerbation. METHODS: A prospective cohort study of
      general medicine outpatients seen at one of seven Veterans Affairs (VA) medical
      centers who returned health screening questionnaires. Three screening
      questionnaires, AUDIT-C (0 to 12 points), CAGE (0 to 4 points), and a single item
      about the frequency of drinking six or more drinks on an occasion (binge
      drinking), were used to classify alcohol consumption. The main outcome, COPD
      exacerbation, was based on primary VA discharge diagnosis (International
      Classification of Diseases, Ninth Revision) or outpatient diagnosis of COPD
      accompanied by prescriptions for either antibiotics or prednisone within 2 days.
      RESULTS: Among the 30,503 patients followed up for a median of 3.35 years, those
      patients with AUDIT-C scores > or = 6, CAGE scores > or = 2, or who reported
      binge drinking at least weekly were at an increased risk of COPD exacerbation in
      age-adjusted analysis. Adjusted hazard ratios were 1.4 (95% confidence interval
      [CI], 1.1 to 1.7) for AUDIT-C score > or = 6, 1.4 (95% CI, 1.3 to 1.5) for CAGE
      score > or = 2, and 1.6 (95% CI, 1.2 to 2.2) for those who reported binge
      drinking daily or almost daily. However, with adjustment for measures of tobacco
      use, the association between alcohol consumption and increased risk of COPD
      exacerbation was no longer evident. CONCLUSIONS: Alcohol consumption, whether
      quantified by AUDIT-C, CAGE score, or binge drinking, was not associated with an
      increased risk of COPD exacerbation independent of tobacco use.

PMID- 18625672
TI  - A possible association between suspected restrictive pattern as assessed by
      ordinary pulmonary function test and the metabolic syndrome.
AB  - BACKGROUND: Impaired restrictive pulmonary function has been reported to be
      associated with insulin resistance and metabolic abnormalities. However, the
      possible association of restrictive pulmonary defect with metabolic syndrome
      (MetS) is not well understood. We examined the association in comparison with C
      reactive protein (CRP), which is a predictor for MetS. METHODS: We recruited
      2,396 apparently healthy adults and investigated the associations among pulmonary
      function, metabolic abnormality, and MetS, as defined by three different
      criteria. Abnormal pulmonary function was evaluated by both continuous pulmonary
      function variables including the percentage of predicted FVC (%PFVC) and a
      clinical category defined according to the American Thoracic Society/European
      Respiratory Society guidelines. RESULTS: CRP and %PFVC, but not FEV1/FVC ratio,
      were significantly correlated with metabolic abnormalities even after adjustment
      for confounders including waist circumference. After adjustment for age, sex, and
      height, the odds ratios (ORs) of a restrictive pattern (RP), as defined by a
      reduced FVC and a normal FEV1/FVC ratio using the lower limit of normal and RP
      substitutively defined by reduced FVC and an FEV1/FVC ratio of > or = 85% for
      MetS, were 1.76 to 2.52 (p < 0.05 to < 0.0001) and 1.87 to 2.28 (p < 0.05 to <
      0.01), respectively. The obstructive pattern (OP) was not significantly
      associated with any MetS criteria. A moderate-to-severe RP, but not a high CRP
      level (> 3.0 mg/L), was consistently associated with the three MetS criteria (OR,
      2.08 to 3.57; p < 0.05 to < 0.01), even after adjustment for confounders.
      CONCLUSION: Impaired restrictive pulmonary function, but not OP, might be
      associated with metabolic disorders and MetS in a severity-dependent manner.

PMID- 18625673
TI  - Perioperative risk factors for prolonged mechanical ventilation following cardiac
      surgery in neonates and young infants.
AB  - BACKGROUND: Prolonged mechanical ventilation (PMV) after cardiac surgery in
      children is associated with a high postoperative morbidity and mortality, as well
      as increased ICU and hospital resource utilization. Little has been done to
      identify the predictors of PMV in neonates and young infants. This study was
      performed to evaluate the perioperative risk factors for PMV in neonates and
      young infants undergoing cardiac surgery. METHODS: Clinical records of 172
      consecutive children aged < or = 3 months were reviewed. PMV was defined as
      mechanical ventilation (MV) > or = 72 h following operation. After univariate
      analysis, a stepwise logistic regression analysis was used to evaluate the
      independent risk factors for PMV following cardiac surgery. The predictive
      ability of risk factors for PMV was assessed using an area under the receiver
      operating characteristic (ROC) curve. RESULTS: Sixty-one patients required PMV
      after cardiac surgery. The median duration of MV was 150 h in PMV patients, while
      it was 28 h in non-PMV patients. The independent risk factors for PMV were risk
      adjustment for surgery for congenital heart disease (RACHS)-1 (p = 0.041),
      nosocomial pneumonia (p = 0.001), low cardiac output syndrome (LCOS) [p = 0.001],
      postoperative cumulative positive fluid balance (p = 0.032), and extubation
      failure (EF) [p = 0.027]. The value for the ROC curve was 0.940. CONCLUSIONS: The
      present results strongly suggest that RACHS-1, nosocomial pneumonia, LCOS, fluid
      retention postoperatively, and EF are risk factors for PMV in neonates and young
      infants undergoing reparative surgery for congenital heart disease.

PMID- 18625674
TI  - Patterns of domestic activity and ambulatory oxygen usage in COPD.
AB  - BACKGROUND: The aim of this study was to examine patterns of domestic activity
      and ambulatory oxygen usage in patients with COPD in their domestic environment.
      METHODS: Twenty patients (14 men; mean age, 73.4 years [SD, 6.8 years]; FEV1, 1.0
      L [SD, 0.5 L]) with stable COPD were recruited after completing a 7-week
      pulmonary rehabilitation program. Patients were either hypoxic at rest or had
      desaturation during exercise. Patients were randomized to an 8-week, double
      blind, placebo-controlled trial of cylinder oxygen vs cylinder air. Total
      domestic physical activity and health-related quality of life (HRQL) measures
      were recorded before and after intervention. RESULTS: There were no significant
      changes in domestic activity or HRQL measures after the intervention for either
      cylinder oxygen or cylinder air, except for a worsening of the Chronic
      Respiratory Questionnaire dyspnea domain on cylinder air. There was a significant
      increase in mean duration (minutes per day) of cylinder use (p < 0.05) between
      weeks 1 vs 7 and weeks 1 vs 8 for the oxygen group. However, when comparing the
      two groups together, there were no between-group differences in cylinder use or
      time spent outside the home. Over the 8 weeks the majority of patients were using
      the cylinders in the home rather than outside, however, the number of times
      patients reported using the cylinders outside the home increased over the 8 weeks
      for the oxygen group. CONCLUSION: In the short term, ambulatory oxygen therapy is
      not associated with improvements in physical activity, HRQL, or time spent away
      from home. However, the use of cylinder oxygen increased over the 8 weeks
      compared to cylinder air. Patients need time to learn how to use oxygen, and
      ambulatory oxygen appears to enhance activities rather than increase them.

PMID- 18625675
TI  - Expression of Ig-like transcript 4 inhibitory receptor in human non-small cell
      lung cancer.
AB  - BACKGROUND: Human Ig-like transcript 4 (ILT-4) is a member of the inhibitory
      receptor family for immune function. Little is known about the expression levels
      of ILT-4 in tumor cells. METHODS: We have studied the expression levels of ILT-4
      both in vitro in cancer cell lines and in vivo in tumor tissues from 70 patients
      with non-small cell lung cancer (NSCLC) by reverse transcriptase-polymerase chain
      reaction, fluorescence-activated cell sorting, and immunohistochemical analysis.
      RESULTS: Three cancer cell lines (H1299, A549, and U1810) express ILT-4 messenger
      RNA, and only two cell lines (H1299 and A549) express ILT-4 protein on the cell
      surface. Approximately 37.1% of 70 tumor tissue samples express ILT-4, which is
      localized in the cell membrane and cytoplasm. In addition, tumor cells and
      stromal and plasma cells also express ILT-4. The number of infiltrating lymphoid
      cells in the tumor tissues that express B7-H3 was much lower than those that did
      not, but there is no significant correlation between ILT-4 expression and disease
      progression including nodal metastasis. CONCLUSIONS: These findings suggest that
      ILT-4 is frequently expressed in both tumor and stromal cells of NSCLC, and it
      might play an important role in regulation of the host immune system.

PMID- 18625676
TI  - Sitaxsentan for the treatment of pulmonary arterial hypertension: a 1-year,
      prospective, open-label observation of outcome and survival.
AB  - BACKGROUND: Despite advances in the management of pulmonary arterial hypertension
      (PAH), the mortality rate remains excessive. Long-term efficacy evaluations are
      needed to guide therapeutic management. The purpose of this study is to present 1
      year observational data with two endothelin antagonists, sitaxsentan and
      bosentan, in a prospective, open-label study. METHODS: The present study was a
      prospective, international, multicenter, randomized, open-label extension of the
      Sitaxsentan To Relieve Impaired Exercise-2 trial. All-cause mortality, time to
      discontinuation (all causes) from monotherapy, time to discontinuation due to
      adverse events, time to elevations in and time to discontinuation due to elevated
      hepatic transaminases, and time to first clinical worsening event were evaluated.
      Patients initially receiving sitaxsentan at 50 mg were excluded from the main
      analysis. The distributions of time-to-event variables are estimated using Kaplan
      Meier methods, and treatment effects are evaluated using the Cox proportional
      hazards model. RESULTS: Patients treated with sitaxsentan at 100 mg had 96%
      overall survival and a 34% risk for a clinical worsening event by 1 year. In
      addition, there was a 6% risk of elevated aspartate aminotransferase (AST) and/or
      alanine aminotransferase (ALT) levels > 3 x upper limit of normal range (ULN) at
      1 year and a 15% risk of discontinuation due to adverse events. Patients treated
      with bosentan had 88% overall survival and a 40% risk of a clinical worsening
      event by 1 year. In addition, there was a 14% risk for elevated AST and/or ALT
      levels > 3 x ULN at 1 year and a 30% risk of discontinuation due to adverse
      events. CONCLUSIONS: At 1 year, sitaxsentan therapy appears safe and efficacious
      for patients with PAH; reductions in mortality and the risk for clinical
      worsening events provide support for durability of efficacy.

PMID- 18625677
TI  - Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell
      development and effector function.
AB  - Adenosine is an immunosuppressive nucleoside, and adenosine A(2A) receptors
      inhibit T-cell activation. We investigated the role of A(2A) receptors in
      regulating T helper (Th)1- and Th2-cell development and effector function. A(2A)
      receptor stimulation suppressed the development of T-cell receptor (TCR) 
      stimulated naive T cells into both Th1 and Th2 cells, as indicated by decreased
      IFN-gamma production by cells developed under Th1-skewing conditions and
      decreased interleukin (IL) -4, IL-5, and IL-10 production by cells developed
      under Th2-skewing conditions. Using A(2A) receptor-deficient mice, we demonstrate
      that A(2A) receptor activation inhibits Th1- and Th2-cell development by
      decreasing the proliferation and IL-2 production of naive T cells, irrespective
      of whether the cells are expanded under Th1- or Th2-skewing environment. Using in
      vivo established Th1 and Th2 cells, we further demonstrate the nonselective
      nature of A(2A) receptor-mediated immunosuppressive effects, because A(2A)
      receptor activation decreased IFN-gamma and IL-4 secretion and mRNA level of TCR
      stimulated effector Th1 and Th2 cells, respectively. A(2A) receptor mRNA
      expression in both Th1 and Th2 effector cells increased following TCR
      stimulation. In summary, these data demonstrate that A(2A) receptor activation
      has strong inhibitory actions during early developmental, as well as late
      effector, stages of Th1- and Th2-cell responses.

PMID- 18625678
TI  - Evidence-based biosafety: a review of the principles and effectiveness of
      microbiological containment measures.
AB  - We examined the available evidence on the effectiveness of measures aimed at
      protecting humans and the environment against the risks of working with
      genetically modified microorganisms (GMOs) and with non-GMO pathogenic
      microorganisms. A few principles and methods underlie the current biosafety
      practice: risk assessment, biological containment, concentration and enclosure,
      exposure minimization, physical containment, and hazard minimization. Many of the
      current practices are based on experience and expert judgment. The effectiveness
      of biosafety measures may be evaluated at the level of single containment
      equipment items and procedures, at the level of the laboratory as a whole, or at
      the clinical-epidemiological level. Data on the containment effectiveness of
      equipment and laboratories are scarce and fragmented. Laboratory-acquired
      infections (LAIs) are therefore important for evaluating the effectiveness of
      biosafety. For the majority of LAIs there appears to be no direct cause,
      suggesting that failures of biosafety were not noticed or that containment may
      have been insufficient. The number of reported laboratory accidents associated
      with GMOs is substantially lower than that of those associated with non-GMOs. It
      is unknown to what extent specific measures contribute to the overall level of
      biosafety. We therefore recommend that the evidence base of biosafety practice be
      strengthened.

PMID- 18625679
TI  - Pertussis vaccination for health care workers.
AB  - Pertussis, an acute respiratory infection caused by Bordetella pertussis,
      classically manifests as a protracted cough illness. The incidence of pertussis
      in the United States has been increasing in recent years. Immunity wanes after
      childhood vaccination, leaving adolescents and adults susceptible to infection.
      The transmission of pertussis in health care settings has important medical and
      economic consequences. Acellular pertussis booster vaccines are now available for
      use and have been recommended for all adolescents and adults. These vaccines are
      safe, immunogenic, and effective. Health care workers are a priority group for
      vaccination because of their increased risk of acquiring infection and the
      potential to transmit pertussis to high-risk patients. Health care worker
      vaccination programs are likely to be cost-effective, but further research is
      needed to determine the acceptability of pertussis vaccines among health care
      workers, the duration of immunity after booster doses, and the impact of
      vaccination on the management of pertussis exposures in health care settings.

PMID- 18625680
TI  - Increasing importance of Balamuthia mandrillaris.
AB  - Balamuthia mandrillaris is an emerging protozoan parasite, an agent of
      granulomatous amoebic encephalitis involving the central nervous system, with a
      case fatality rate of >98%. This review presents our current understanding of
      Balamuthia infections, their pathogenesis and pathophysiology, and molecular
      mechanisms associated with the disease, as well as virulence traits of Balamuthia
      that may be potential targets for therapeutic interventions and/or for the
      development of preventative measures.

PMID- 18625681
TI  - Polymyxins revisited.
AB  - The global emergence of multidrug-resistant gram-negative bacilli has spurred a
      renewed interest in polymyxins. Once discarded due to concerns regarding
      nephrotoxicity and neurotoxicity, polymyxins now hold an important role in the
      antibiotic armamentarium. However, more reliable information is needed to
      determine the optimal dosing of these agents. Also, unanswered questions
      regarding in vitro testing remain, including questions regarding the reliability
      of automated systems and the establishment of appropriate breakpoints for
      defining susceptibility. Most contemporary clinical studies examining the use of
      these agents have involved patients with infections due to multidrug-resistant
      Pseudomonas aeruginosa and Acinetobacter baumannii strains. It has been
      reassuring that polymyxin therapy for resistant bacteria has resulted in clinical
      responses and toxicity rates similar to those for carbapenem therapy for
      susceptible isolates. While most surveillance studies demonstrated high rates of
      susceptibility, several reports noted the emergence of polymyxin-resistant
      nosocomial pathogens. Polymyxins have assumed an important antibiotic niche for
      therapy for hospital-acquired infections; further studies defining the optimal
      use of these agents will likely extend the duration of their clinical usefulness.

PMID- 18625682
TI  - Malaria chemoprophylaxis: strategies for risk groups.
AB  - The risk of malaria for travelers varies from region to region and depends on the
      intensity of transmission, the duration of the stay in the area of endemicity,
      the style of travel, and the efficacy of preventive measures. The decision to
      recommend chemoprophylaxis to travelers to areas with a low risk of malarial
      infection is especially difficult because the risk of infection must be balanced
      with the risk of experiencing side effects. If the risk of side effects by far
      exceeds the risk of infection, the traveler needs information on measures against
      mosquito bites and advice on prompt diagnosis and self-treatment. The risk is
      difficult to quantify, and the absolute risk for travelers to most areas is not
      known, especially because the populations at risk are unknown. We propose here
      that the best approximation of the risk to the traveler to a specific area is to
      use the risk to the indigenous population as a guideline for the risk to the
      traveler, and we provide examples on how risk in the indigenous population can be
      used for the estimation of risk of malarial infection for travelers. Special
      groups are long-term visitors and residents, who often perceive risk differently,
      cease using chemoprophylaxis, and rely on self-diagnosis and treatment. For long
      term visitors, the problem of fake drugs needs to be discussed. Strategies for
      chemoprophylaxis and self-treatment of pregnant women and small children are
      discussed. So far, malaria prophylaxis is recommended to prevent Plasmodium
      falciparum infections, and primaquine prophylaxis against persistent Plasmodium
      vivax and Plasmodium ovale infections in travelers is not recommended.

PMID- 18625683
TI  - Bacterial, fungal, parasitic, and viral myositis.
AB  - Infectious myositis may be caused by a broad range of bacterial, fungal,
      parasitic, and viral agents. Infectious myositis is overall uncommon given the
      relative resistance of the musculature to infection. For example, inciting
      events, including trauma, surgery, or the presence of foreign bodies or
      devitalized tissue, are often present in cases of bacterial myositis. Bacterial
      causes are categorized by clinical presentation, anatomic location, and causative
      organisms into the categories of pyomyositis, psoas abscess, Staphylococcus
      aureus myositis, group A streptococcal necrotizing myositis, group B
      streptococcal myositis, clostridial gas gangrene, and nonclostridial myositis.
      Fungal myositis is rare and usually occurs among immunocompromised hosts.
      Parasitic myositis is most commonly a result of trichinosis or cystericercosis,
      but other protozoa or helminths may be involved. A parasitic cause of myositis is
      suggested by the travel history and presence of eosinophilia. Viruses may cause
      diffuse muscle involvement with clinical manifestations, such as benign acute
      myositis (most commonly due to influenza virus), pleurodynia (coxsackievirus B),
      acute rhabdomyolysis, or an immune-mediated polymyositis. The diagnosis of
      myositis is suggested by the clinical picture and radiologic imaging, and the
      etiologic agent is confirmed by microbiologic or serologic testing. Therapy is
      based on the clinical presentation and the underlying pathogen.

PMID- 18625684
TI  - Epidemiologic, experimental, and clinical links between respiratory syncytial
      virus infection and asthma.
AB  - Virtually all children experience respiratory syncytial virus (RSV) infection at
      least once during the first 2 years of life, but only a few develop bronchiolitis
      and more severe disease requiring hospitalization, usually in the first 6 months
      of life. Children who recover from RSV-induced bronchiolitis are at increased
      risk for the development of recurrent wheeze and asthma in later childhood.
      Recent studies suggest that there is an association between RSV-induced
      bronchiolitis and asthma within the first decade of life but that this
      association is not significant after age 13. Despite the considerable progress
      made in our understanding of several aspects of respiratory viral infections,
      further work needs to be done to clarify the molecular mechanisms of early
      interactions between virus and host cell and the role of host gene products in
      the infection process. This review provides a critical appraisal of the
      literature in epidemiology and experimental research which links RSV infection to
      asthma. Studies to date demonstrate that there is a significant association
      between RSV infection and childhood asthma and that preventing severe primary RSV
      infections can decrease the risk of childhood asthma.

PMID- 18625685
TI  - Host-pathogen interactions in Campylobacter infections: the host perspective.
AB  - Campylobacter is a major cause of acute bacterial diarrhea in humans worldwide.
      This study was aimed at summarizing the current understanding of host mechanisms
      involved in the defense against Campylobacter by evaluating data available from
      three sources: (i) epidemiological observations, (ii) observations of patients,
      and (iii) experimental observations including observations of animal models and
      human volunteer studies. Analysis of available data clearly indicates that an
      effective immune system is crucial for the host defense against Campylobacter
      infection. Innate, cell-mediated, and humoral immune responses are induced during
      Campylobacter infection, but the relative importance of these mechanisms in
      conferring protective immunity against reinfection is unclear. Frequent exposure
      to Campylobacter does lead to the induction of short-term protection against
      disease but most probably not against colonization. Recent progress in the
      development of more suitable animal models for studying Campylobacter infection
      has opened up possibilities to study the importance of innate and adaptive
      immunity during infection and in protection against reinfection. In addition,
      advances in genomics and proteomics technologies will enable more detailed
      molecular studies. Such studies combined with better integration of host and
      pathogen research driven by epidemiological findings may truly advance our
      understanding of Campylobacter infection in humans.

PMID- 18625688
TI  - Biodistribution and plasma protein binding of zoledronic acid.
AB  - The bisphosphonate zoledronic acid is a potent inhibitor of osteoclast-mediated
      bone resorption. To investigate drug biodistribution and elimination, (14)C
      zoledronic acid was administered intravenously to rats and dogs in single or
      multiple doses and assessed for its in vitro blood distribution and plasma
      protein binding in rat, dog, and human. Drug exposure in plasma, bones, and
      noncalcified tissues was investigated up to 240 days in rats and 96 h in dogs
      using radiometry after dissection. Drug biodistribution in the rat and within
      selected bones from dog was assessed by autoradiography. Concentrations of
      radioactivity showed a rapid decline in plasma and noncalcified tissue but only a
      slow decline in bone, to approximately 50% of peak at 240 days post dose, whereas
      the terminal half-lives (50-200 days) were similar in bone and noncalcified
      tissues, suggesting redistribution of drug from the former rather than prolonged
      retention in the latter. Uptake was highest in cancellous bone and axial
      skeleton. At 96 h after dose, the fraction of dose excreted was 36% in rat and
      60% in dog; 94 to 96% of the excreted radioactivity was found in urine.
      Blood/plasma concentration ratios were 0.52 to 0.59, and plasma protein binding
      of zoledronic acid was moderate to low in all species. The results suggest that a
      fraction of zoledronic acid is reversibly taken up by the skeleton, the
      elimination of drug is mainly by renal excretion, and the disposition in blood
      and noncalcified tissue is governed by extensive uptake into and slow release
      from bone.

PMID- 18625686
TI  - Epidemiology, etiology, pathogenesis, and diagnosis of recurrent bacterial
      meningitis.
AB  - Recurrent bacterial meningitis is a rare phenomenon and generally poses a
      considerable diagnostic challenge to the clinician. Ultimately, a structured
      approach and early diagnosis of any underlying pathology are crucial to prevent
      further episodes and improve the overall outcome for the affected individual. In
      this article, we are reviewing the existing literature on this topic over the
      last two decades, encompassing 363 cases of recurrent bacterial meningitis
      described in 144 publications. Of these cases, 214 (59%) were related to
      anatomical problems, 132 (36%) were related to immunodeficiencies, and 17 (5%)
      were related to parameningeal infections. The review includes a detailed
      discussion of the underlying pathologies and microbiological aspects as well as
      recommendations for appropriate diagnostic pathways for investigating this
      unusual entity.

PMID- 18625689
TI  - Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to
      dexamethasone and a false positive outcome of inferior petrosal sinus sampling.
AB  - CONTEXT: Establishing the cause of Cushing's syndrome (CS) can be a considerable
      challenge, in particular in ectopic adrenocorticotropic hormone (ACTH) syndrome,
      and often requires a combination of biochemical tests and imaging procedures.
      SUBJECT: A 27-year-old man presented with signs of CS. P-ACTH levels were three
      times above the upper limit of normal (ULN) and free urinary cortisol around 2000
      nmol/24 h. The work-up showed remarkable results. RESULTS: A 2-day low-dose
      dexamethasone suppression test demonstrated paradoxical increases in cortisol.
      Sampling from the bilateral inferior petrosal sinus sampling (BIPSS) showed a
      central to peripheral ACTH ratio of 4.7 after corticotrophin-releasing hormone
      (CRH) stimulation, i.e. indicated pituitary disease, but magnetic resonance
      imaging of the pituitary was normal. Computed tomography (CT) scan of the lungs
      showed two oval-shaped masses, 1.3 x 1.8 and 1.3 x 2 cm, in the middle lobe. Both
      were positive at somatostatin receptor scintigraphy, compatible with tumors or
      inflammatory lesions. Subsequently, (11)C-5-hydroxytryptophan-PET showed distinct
      uptake in the tumors but not elsewhere. Two carcinoids situated 3 cm apart, both
      staining for ACTH, were removed at surgery. CONCLUSION: This unique case with
      dual bronchial carcinoids inducing hypercortisolism illustrates the problems with
      identifying the source of ACTH in CS. Possibly, an abnormal regulation of ACTH
      production in response to dexamethasone, or steroid-induced tumor necrosis,
      explains the paradoxical outcome at dexamethasone suppression, and the false
      positive result at BIPSS reflects an unusual sensitivity of the pituitary
      corticotrophs to CRH in this patient. The work-up illustrates the great value of
      (11)C-5-hydroxytryptophan-PET as a diagnostic procedure when other investigations
      have produced ambiguous results.

PMID- 18625690
TI  - Low dose cabergoline for hyperprolactinaemia is not associated with clinically
      significant valvular heart disease.
AB  - OBJECTIVE: Recent trials suggest that using ergot-derived dopamine agonists such
      as cabergoline in the treatment of Parkinson's disease is associated with an
      increased risk of valvular heart disease. However, the dose of cabergoline used
      to treat hyperprolactinaemia is considerably less than that used in Parkinson's
      disease. DESIGN AND METHODS: A cross-sectional comparative assessment. Forty-four
      patients treated with cabergoline for hyperprolactinaemia underwent transthoracic
      echocardiography and were compared with 566 sequential subjects complaining of
      palpitations, taken from a contemporary echocardiography database. RESULTS: The
      mean cumulative dose of cabergoline in the cases was 311 mg. There was no
      significant, severe or moderate, right- or left-sided valvular regurgitation in
      either group. Left heart: in the mitral and aortic valves, the rate of mild and
      trivial valvular regurgitation was not different between the two groups. Right
      heart: mild tricuspid and pulmonary regurgitation on colour Doppler alone was
      increased significantly in the cabergoline group, odds ratios of 3.1 and 7.8
      respectively (95% confidence interval 1.0-9.6 and 0.8-78.4, P=0.04 and P<0.0001
      respectively). CONCLUSION: Cabergoline at doses sufficient to suppress
      hyperprolactinaemia for a period of 3-4 years is not associated with an increased
      risk of clinically significant valvular regurgitation.

PMID- 18625691
TI  - Human chorionic gonadotropin measurements in parathyroid carcinoma.
AB  - OBJECTIVE: Preoperatively, it is difficult to differentiate between parathyroid
      cancer (PtCa) and severe primary hyperparathyroidism (PHPT) due to a benign
      tumor. Human chorionic gonadotropin (hCG) is a tumor marker in trophoblastic and
      nontrophoblastic cancers and hyperglycosylated hCG is increased in hCG-secreting
      malignancies. We investigated whether hCG can distinguish PtCa cancer from benign
      disease and add prognostic information. DESIGN: Observational study. METHODS:
      Measurement of urinary hCG (total and malignant isoforms) and serum malignant hCG
      in 8 subjects with PtCa and in 18 subjects with PHPT (measurement of urine in ten
      and serum in eight). RESULTS: Total urinary hCG was normal in the benign PHPT
      control subjects (range: 0-17 fmol/mg Cr; nl<50). In the PtCa subjects, three had
      normal total urinary hCG levels and survived complication free for at least 2
      years; three had persistently elevated total urinary hCG levels (range: 217-1986
      fmol/mg Cr) and sustained hip fracture (n=3) and died (n=2) within 3 and 6 months
      respectively; two had a rise in total urinary hCG and had hip fracture (n=1) and
      died (n=2) within 4 and 10 months respectively. Elevated urinary hCG was of the
      malignant hyperglycosylated isoform. Serum malignant hyperglycosylated hCG values
      in all of the cancer patients exceeded the maximal serum malignant hCG level of
      the PHPT subjects with benign disease (3.77 pmol/l). CONCLUSION: hCG, especially
      its hyperglycosylated isoform, might add diagnostic and prognostic information in
      PtCa. Further studies would help to elucidate the role of hCG as a potential
      tumor marker in this disease.

PMID- 18625692
TI  - Determinants of symptoms in functional dyspepsia: gastric sensorimotor function,
      psychosocial factors or somatisation?
AB  - BACKGROUND: Gastric sensorimotor dysfunction, psychosocial factors and
      somatisation are all implicated in symptom generation in functional dyspepsia
      (FD). AIM: To determine the relative contribution of each of these factors to
      overall dyspeptic symptom severity and weight loss in FD. METHODS: In 201
      consecutive tertiary care patients with FD (mean age 40.1 (SD 12.6) years),
      gastric sensorimotor function was studied using barostat (sensitivity, compliance
      and accommodation). Psychosocial factors (depression and anxiety disorders,
      positive and negative affect, perceived stress, alexithymia and history of
      abuse), somatisation and co-morbid irritable bowel syndrome (IBS) and chronic
      fatigue symptoms were assessed using self-report questionnaires. Variables were
      correlated with dyspepsia symptom severity (DSS) and weight loss. Hierarchical
      multiple linear regression was used to identify determinants of DSS and weight
      loss. RESULTS: Multiple linear regression identified the following determinants
      of DSS: gastric sensitivity (beta = 0.77, p = 0.25), depression (beta = 0.12, p =
      0.06) and somatisation (beta = 0.48, p<0.0001) (controlling for age and
      occupation, R(2) = 0.29, p<0.0001). The effect of depression on DSS is partially
      mediated by somatisation. Gastric sensitivity (beta = 2.87, p = 0.08), history of
      childhood sexual abuse (beta = 9.37, p = 0.0006), depression (beta = 0.19, p =
      0.24) and somatisation (beta = 0.67, p = 0.01) are independent determinants of
      weight loss (controlling for gender and occupation, R(2) = 0.42, p<0.0001). The
      effect of depression on weight loss is fully mediated by somatisation.
      CONCLUSION: Symptom severity and weight loss in FD are determined by psychosocial
      factors (depression, abuse history) and somatisation, and only to a lesser extent
      by gastric sensorimotor function. The importance of psychosocial factors and
      somatisation compared to gastric sensorimotor function is most pronounced in
      hypersensitive patients.

PMID- 18625693
TI  - Transcriptional and post-translational regulation of Flip, an inhibitor of Fas
      mediated apoptosis, in human gut inflammation.
AB  - OBJECTIVE: Defects in Fas-mediated apoptosis are supposed to contribute to the
      accumulation of T lymphocytes in the gut of patients with Crohn's disease (CD).
      This phenomenon has been functionally linked with the elevated expression of
      Flip, an inhibitor of Fas-mediated apoptosis. In this study, the molecular
      mechanisms that control Flip in CD were examined. METHODS: Paired colonic
      biopsies of patients with CD, patients with ulcerative colitis (UC) and normal
      controls were analysed for Flip by real-time PCR and western blotting. Flip was
      also evaluated in CD3(+) lamina propria lymphocytes (T-LPLs) cultured with tosyl
      phenylalanyl chloromethyl ketone (TPCK; a nuclear factor-kappaB (NF-kappaB)
      inhibitor), AG490 (a Janus kinase 2 (Jak2)/signal transducer and activator of
      transcription (Stat) inhibitor) or 17-desmethoxy-17-N,N-dimethylamino
      geldanamycin (DMAG; an inhibitor of heat shock protein 90). The rate of apoptosis
      was examined by flow cytometry. RESULTS: In CD, upregulation of Flip occurred at
      both the RNA and protein level. Treatment of CD CD3(+) T-LPLs with TPCK or AG490
      markedly reduced Flip RNA, suggesting a role for NF-kappaB and Jak/Stat pathways
      in the transcriptional control of Flip in this condition. Consistently, both TPCK
      and AG490 sensitised CD T-LPLs to Fas-mediated apoptosis. Flip protein in cells
      from normal gut was rapidly degraded by the proteasome pathway. In contrast, in
      inflamed gut of both CD and UC patients, there was a reduced degradation of Flip
      via the ubiquitin-proteasome-dependent pathway, but Flip expression can be
      decreased by DMAG. CONCLUSIONS: The data demonstrate that Flip is regulated at
      both the transcriptional and post-translational level in CD, and indicate that in
      the normal but not inflamed gut Flip is degraded via the ubiquitin-proteasome
      dependent pathway.

PMID- 18625694
TI  - A high incidence of MSH6 mutations in Amsterdam criteria II-negative families
      tested in a diagnostic setting.
AB  - BACKGROUND AND AIMS: In Lynch syndrome, the clinical phenotype in MSH6 mutation
      families differs from that in MLH1 and MSH2 families. Therefore, MSH6 mutation
      families are less likely to fulfil diagnostic criteria such as the Amsterdam II
      criteria (AC II) and the revised Bethesda guidelines (rBG), and will be
      underdiagnosed. The aim of the present study was to evaluate the contribution of
      MSH6 gene mutations in families that were analysed for Lynch syndrome in a
      diagnostic setting. METHODS: Families that had molecular analysis for Lynch
      syndrome were included in this study. Complete molecular screening of the MLH1,
      MSH2 and MSH6 genes was performed in all families. Microsatellite instability
      (MSI) and immunohistochemical (IHC) analysis was performed in almost all
      families. Clinical data were collected from medical records and family pedigrees.
      RESULTS: A total of 108 families were included. MSI and IHC analysis was
      performed in 97 families, and in 40 an MSI-high phenotype with absent protein
      expression was found. Germline mutation analysis detected mutations in 23
      families (7 MLH1, 4 MSH2 and 12 MSH6). The majority of MSH6 families were AC II
      negative, but fulfilled the rBG. CONCLUSIONS: There is a high incidence of MSH6
      mutations in families tested for Lynch syndrome in a diagnostic setting. Many of
      these families remain underdiagnosed using the AC II. The rBG are more useful to
      select these families for further analysis. However, to optimise the detection of
      MSH6 families, MSI and IHC analysis should also be performed in families with
      clustering of late-onset endometrial carcinoma.

PMID- 18625695
TI  - A pH-sensitive, neurogenic pathway mediates disease severity in a model of post
      ERCP pancreatitis.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has a high risk
      of pancreatitis although the underlying mechanisms are unclear. Transient
      receptor potential vanilloid 1 (TRPV1) is a cation channel expressed on C and
      Adelta fibres of primary sensory neurons and is activated by low pH. TRPV1
      activation causes release of inflammatory mediators that produce oedema and
      neutrophil infiltration. We previously demonstrated that neurogenic factors
      contribute to the pathogenesis of pancreatitis. Resiniferatoxin (RTX) is a TRPV1
      agonist that, in high doses, defunctionalises C and Adelta fibres. When we
      discovered that the pH of radio-opaque contrast solutions used for ERCP was 6.9,
      we hypothesised that low pH may contribute to the development of contrast-induced
      pancreatitis via activation of TRPV1. METHODS: Rats underwent equal pressure
      pancreatic ductal injection of contrast solutions at varying pH with or without
      RTX. RESULTS: Contrast solution (pH 6.9) injected into the pancreatic duct caused
      a significant increase in pancreatic oedema, serum amylase, neutrophil
      infiltration, and histological damage. Solutions of pH 7.3 injected at equal
      pressure caused little damage. The severity of the pancreatitis was significantly
      increased by injection of solutions at pH 6.0. To determine if the effects of low
      pH were mediated by TRPV1, RTX was added to the contrast solutions. At pH levels
      of 6.0 and 6.9, RTX significantly reduced the severity of pancreatitis.
      CONCLUSIONS: Contrast solutions with low pH contribute to the development of
      pancreatitis through a TRPV1-dependent mechanism. It is possible that increasing
      the pH of contrast solution and/or adding an agent that inhibits primary sensory
      nerve activation may reduce the risk of post-ERCP pancreatitis.

PMID- 18625697
TI  - Gallbladder nitric oxide.

PMID- 18625696
TI  - Host- rather than virus-related factors reduce health-related quality of life in
      hepatitis C virus infection.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is associated with decreased health
      related quality of life (HRQOL). Although HCV has been suggested to directly
      impair neuropsychiatric functions, other factors may also play a role. PATIENTS
      AND METHODS: In this cross-sectional study, we assessed the impact of various
      host-, disease- and virus-related factors on HRQOL in a large, unselected
      population of anti-HCV-positive subjects. All individuals (n = 1736) enrolled in
      the Swiss Hepatitis C Cohort Study (SCCS) were asked to complete the Short Form
      36 (SF-36) and the Hospital Anxiety Depression Scale (HADS). RESULTS: 833
      patients (48%) returned the questionnaires. Survey participants had significantly
      worse scores in both assessment instruments when compared to a general
      population. By multivariable analysis, reduced HRQOL (mental and physical summary
      scores of SF-36) was independently associated with income. In addition, a low
      physical summary score was associated with age and diabetes, whereas a low mental
      summary score was associated with intravenous drug use. HADS anxiety and
      depression scores were independently associated with income and intravenous drug
      use. In addition, HADS depression score was associated with diabetes. None of the
      SF-36 or HADS scores correlated with either the presence or the level of serum
      HCV RNA. In particular, SF-36 and HADS scores were comparable in 555 HCV RNA
      positive and 262 HCV RNA-negative individuals. CONCLUSIONS: Anti-HCV-positive
      subjects have decreased HRQOL compared to controls. The magnitude of this
      decrease was clinically important for the SF-36 vitality score. Host and
      environmental, rather than viral factors, seem to impact on HRQOL level.

PMID- 18625687
TI  - Acinetobacter baumannii: emergence of a successful pathogen.
AB  - Acinetobacter baumannii has emerged as a highly troublesome pathogen for many
      institutions globally. As a consequence of its immense ability to acquire or
      upregulate antibiotic drug resistance determinants, it has justifiably been
      propelled to the forefront of scientific attention. Apart from its predilection
      for the seriously ill within intensive care units, A. baumannii has more recently
      caused a range of infectious syndromes in military personnel injured in the Iraq
      and Afghanistan conflicts. This review details the significant advances that have
      been made in our understanding of this remarkable organism over the last 10
      years, including current taxonomy and species identification, issues with
      susceptibility testing, mechanisms of antibiotic resistance, global epidemiology,
      clinical impact of infection, host-pathogen interactions, and infection control
      and therapeutic considerations.

PMID- 18625698
TI  - Inhibition of chalcone synthase expression in anthers of Raphanus sativus with
      Ogura male sterile cytoplasm.
AB  - BACKGROUND AND AIMS: Expression of the mitochondrial gene orf138 causes Ogura
      cytoplasmic male sterility (CMS) in Raphanus sativus, but little is known about
      the mechanism by which CMS takes place. A preliminary microarray experiment
      revealed that several nuclear genes concerned with flavonoid biosynthesis were
      inhibited in the male-sterile phenotype. In particular, a gene for one of the key
      enzymes for flavonoid biosynthesis, chalcone synthase (CHS), was strongly
      inhibited. A few reports have suggested that the inhibition of CHS causes nuclear
      dependent male sterile expression; however, there do not appear to be any reports
      elucidating the effect of CHS on CMS expression. In this study, the expression
      patterns of the early genes in the flavonoid biosynthesis pathway, including CHS,
      were investigated in normal and male-sterile lines. METHODS: In order to
      determine the aberrant stage for CMS expression, the characteristics of male
      sterile anthers are observed using light and transmission electron microscopy for
      several stages of flower buds. The expression of CHS and the other flavonoid
      biosynthetic genes in the anthers were compared between normal and male-sterile
      types using real time RT-PCR. KEY RESULTS: Among the flavonoid biosynthetic genes
      analysed, the expression of CHS was strongly inhibited in the later stages of
      anther development in sterility cytoplasm; accumulation of putative naringenin
      derivatives was also inhibited. CONCLUSIONS: These results show that flavonoids
      play an important role in the development of functional pollen, not only in
      nuclear-dependent male sterility, but also in CMS.

PMID- 18625699
TI  - Quality of informed consent for invasive procedures.
AB  - OBJECTIVE: To assess quality of informed consent among patients undergoing
      procedures and patient's preferences about decision-making. DESIGN: Cross
      sectional survey of hospitalized patients about informed consent before surgery
      or other procedures. Preference for decision-making was elicited in hospitalized
      and ambulatory patients. SETTING: Large academic general hospital and 10 general
      clinics, over the years 2002-04. INTERVENTION: Data of initial survey were
      presented at staff meetings, recommending asking patients to restate what was
      explained to them. MAIN OUTCOME MEASURES: Rate of patient's recall for
      explanations on risks and alternative options; rate of patients preferring
      shared, autonomous and paternalistic modes of decision-making; degree of
      satisfaction from the decision-making. RESULTS: Half of the patients did not
      recall receiving explanations about risks and two-third did not remember
      discussion of alternative options. The intervention failed, <10% of patients
      being asked to re-state what was explained to them. Expectations about decision
      varied: approximately 60% favored shared decision, nearly 20% preferred
      autonomous decision and the remainder wanted physicians to make decisions.
      Satisfaction was rated as good or very good by 80% of patients. CONCLUSIONS: Most
      patients do not remember receiving explanations about risks or alternatives for
      procedures, and physicians resist attempts to improve informed consent. Tools
      should be developed to measure the quality of consent. Since patients
      significantly differ in their preferred mode of decision-making, the informed
      consent should be patient-specific.

PMID- 18625700
TI  - Commentary on Buckner and implications for treatment selection among foster
      children with RAD.
AB  - This commentary discusses possible implications of Buckner's (2008) case study,
      which successfully applied behavioral parent training for a child in out-of-home
      care who was diagnosed with reactive attachment disorder (RAD). The report is
      discussed within the context of recommendations offered by the 2006 APSAC Task
      Force on Attachment Therapy, Reactive Attachment Disorder, and Attachment
      Problems. The discussion also address the question of how well brief evidence
      based parenting models might be accepted by parents or clinicians who have
      presumed that traditional therapies do not work for children diagnosed with RAD
      or that radical and concerning treatments are required.

PMID- 18625701
TI  - cAMP-dependent protein kinase A (PKA) signaling induces TNFR1 exosome-like
      vesicle release via anchoring of PKA regulatory subunit RIIbeta to BIG2.
AB  - The 55-kDa TNFR1 (type I tumor necrosis factor receptor) can be released to the
      extracellular space by two mechanisms, the proteolytic cleavage and shedding of
      soluble receptor ectodomains and the release of full-length receptors within
      exosome-like vesicles. We have shown that the brefeldin A-inhibited guanine
      nucleotide exchange protein BIG2 associates with TNFR1 and selectively modulates
      the release of TNFR1 exosome-like vesicles via an ARF1- and ARF3-dependent
      mechanism. Here, we assessed the role of BIG2 A kinase-anchoring protein (AKAP)
      domains in the regulation of TNFR1 exosome-like vesicle release from human
      vascular endothelial cells. We show that 8-bromo-cyclic AMP induced the release
      of full-length, 55-kDa TNFR1 within exosome-like vesicles via a protein kinase A
      (PKA)-dependent mechanism. Using RNA interference to decrease specifically the
      levels of individual PKA regulatory subunits, we demonstrate that RIIbeta
      modulates both the constitutive and cAMP-induced release of TNFR1 exosome-like
      vesicles. Consistent with its AKAP function, BIG2 was required for the cAMP
      induced PKA-dependent release of TNFR1 exosome-like vesicles via a mechanism that
      involved the binding of RIIbeta to BIG2 AKAP domains B and C. We conclude that
      both the constitutive and cAMP-induced release of TNFR1 exosome-like vesicles
      occur via PKA-dependent pathways that are regulated by the anchoring of RIIbeta
      to BIG2 via AKAP domains B and C. Thus, BIG2 regulates TNFR1 exosome-like vesicle
      release by two distinct mechanisms, as a guanine nucleotide exchange protein that
      activates class I ADP-ribosylation factors and as an AKAP for RIIbeta that
      localizes PKA signaling within cellular TNFR1 trafficking pathways.

PMID- 18625702
TI  - Protein kinase R-dependent regulation of interleukin-10 in response to double
      stranded RNA.
AB  - The double-stranded RNA-activated protein kinase R (PKR) is an important
      component of antiviral defense. PKR participates in different signaling pathways
      in response to various stimuli to regulate translation via phosphorylation of the
      eukaryotic initiation factor 2alpha, and transcription via activating NF-kappaB
      and IRF-1, to induce pro-inflammatory cytokines. Here we show PKR regulates
      interleukin-10 induction in response to double-stranded RNA, bacterial
      lipopolysaccaride, and Sendai virus infection. Using chemical inhibitors,
      dominant negative constructs, and genetic knockouts, we demonstrate that the PKR
      mediated interleukin-10 induction engages JNK and NF-kappaB. Together, our data
      demonstrate the role of PKR in regulating an anti-inflammatory cytokine. The
      findings have significance in antiviral as well as broader innate immune
      responses.

PMID- 18625703
TI  - Sphingolipid metabolism is a crucial determinant of cellular fate in
      nonstimulated proliferating Madin-Darby canine kidney (MDCK) cells.
AB  - The present report was addressed to study the influence of sphingolipid
      metabolism in determining cellular fate. In nonstimulated proliferating Madin
      Darby canine kidney (MDCK) cells, sphingolipid de novo synthesis is branched
      mainly to a production of sphingomyelin and ceramide, with a minor production of
      sphingosylphosphocholine, ceramide 1-phosphate, and sphingosine 1-phosphate.
      Experiments with (32)P as a radioactive precursor showed that sphingosine 1
      phosphate is produced mainly by a de novo independent pathway. Enzymatic
      inhibition of the de novo pathway and ceramide synthesis affected cell number and
      viability only slightly, without changing sphingosine 1-phosphate production. By
      contrast, inhibition of sphingosine kinase-1 activity provoked a significant
      reduction in both cell number and viability in a dose-dependent manner. When
      sphingolipid metabolism was studied, an increase in de novo formed ceramide was
      found, which correlated with the concentration of enzyme inhibitor and the
      reduction in cell number and viability. Knockdown of sphingosine kinase-1
      expression also induced an accumulation of de novo synthesized ceramide,
      provoking a slight reduction in cell number and viability similar to that induced
      by a low concentration of the sphingosine kinase inhibitor. Taken together, our
      results indicate that the level of de novo formed ceramide is controlled by the
      synthesis of sphingosine 1-phosphate, which appears to occur through a de novo
      synthesis-independent pathway, most probably the salvage pathway, that is
      responsible for the MDCK cell fate, suggesting that under proliferating
      conditions, a dynamic interplay exists between the de novo synthesis and the
      salvage pathway.

PMID- 18625704
TI  - Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha
      regulatory axis.
AB  - Angiogenesis is induced by multiple growth factors including vascular endothelial
      growth factor (VEGF) and fibroblast growth factor 2 (FGF2). In vascular
      endothelium VEGF signals through two receptor-tyrosine kinases, VEGFR1 and
      VEGFR2. The VEGFR1 gene encodes both a receptor-tyrosine kinase and a secreted
      splice variant, soluble VEGFR1. Whereas VEGFR1 is essential for vascular
      development, mechanisms that regulate VEGFR1 expression in endothelial cells are
      poorly understood. We demonstrate here that in endothelial cells, FGF2 and
      epidermal growth factor (EGF) signaling induce VEGFR1 mRNA expression in a
      combinatorial fashion. EGF/FGF2-mediated VEGFR1 induction is mediated via
      functional interaction of transcription factors ETS1 and HIF-2alpha. Mechanistic
      analyses revealed that in endothelial cells EGF/FGF2 signaling induces ETS1
      expression, increases HIF-2alpha protein level in absence of hypoxia, and
      recruits both ETS1 and HIF-2alpha to the VEGFR1 chromatin domain. Knockdown of
      ETS1 and HIF-2alpha by RNA interference inhibits EGF/FGF2-induced VEGFR1
      expression, and loss of expression is associated with impaired RNA-polymerase II
      recruitment and histone modifications at the VEGFR1 promoter region. In addition,
      using a mouse embryonic stem cell in vitro differentiation system, we found that
      induction of VEGFR1 in embryoid bodies is also associated with ETS1 and HIF
      2alpha recruitment to the VEGFR1 locus. These results establish an angiogenic
      signal-ETS1/HIF-2alpha axis that regulates the VEGFR1 chromatin domain to induce
      VEGFR1 transcription in endothelial cells and in differentiating embryonic stem
      cells.

PMID- 18625705
TI  - Diarylquinolines are bactericidal for dormant mycobacteria as a result of
      disturbed ATP homeostasis.
AB  - An estimated one-third of the world population is latently infected with
      Mycobacterium tuberculosis. These nonreplicating, dormant bacilli are tolerant to
      conventional anti-tuberculosis drugs, such as isoniazid. We recently identified
      diarylquinoline R207910 (also called TMC207) as an inhibitor of ATP synthase with
      a remarkable activity against replicating mycobacteria. In the present study, we
      show that R207910 kills dormant bacilli as effectively as aerobically grown
      bacilli with the same target specificity. Despite a transcriptional down
      regulation of the ATP synthase operon and significantly lower cellular ATP
      levels, we show that dormant mycobacteria do possess residual ATP synthase
      enzymatic activity. This activity is blocked by nanomolar concentrations of
      R207910, thereby further reducing ATP levels and causing a pronounced
      bactericidal effect. We conclude that this residual ATP synthase activity is
      indispensable for the survival of dormant mycobacteria, making it a promising
      drug target to tackle dormant infections. The unique dual bactericidal activity
      of diarylquinolines on dormant as well as replicating bacterial subpopulations
      distinguishes them entirely from the current anti-tuberculosis drugs and
      underlines the potential of R207910 to shorten tuberculosis treatment.

PMID- 18625706
TI  - Transgenic overexpression of Hdac3 in the heart produces increased postnatal
      cardiac myocyte proliferation but does not induce hypertrophy.
AB  - Class I and II histone deacetylases (HDACs) play vital roles in regulating
      cardiac development, morphogenesis, and hypertrophic responses. Although the
      roles of Hdac1 and Hdac2, class I HDACs, in cardiac hyperplasia, growth, and
      hypertrophic responsiveness have been reported, the role in the heart of Hdac3,
      another class I HDAC, has been less well explored. Here we report that myocyte
      specific overexpression of Hdac3 in mice results in cardiac abnormalities at
      birth. Hdac3 overexpression produces thickening of ventricular myocardium,
      especially the interventricular septum, and reduction of both ventricular
      cavities in newborn hearts. Our data suggest that increased thickness of
      myocardium in Hdac3-transgenic (Hdac3-Tg) mice is due to increased cardiomyocyte
      hyperplasia without hypertrophy. Hdac3 overexpression inhibits several cyclin
      dependent kinase inhibitors, including Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, and
      Cdkn2c. Hdac3-Tg mice did not develop cardiac hypertrophy at 3 months of age,
      unlike previously reported Hdac2-Tg mice. Further, Hdac3 overexpression did not
      augment isoproterenol-induced cardiac hypertrophy when compared with wild-type
      littermates. These findings identify Hdac3 as a novel regulator of cardiac
      myocyte proliferation during cardiac development.

PMID- 18625707
TI  - Plk1 phosphorylation of TRF1 is essential for its binding to telomeres.
AB  - In a search for Polo-like kinase 1 (Plk1) interaction proteins, we have
      identified TRF1 (telomeric repeat binding factor 1) as a potential Plk1 target.
      In this communication we report further characterization of the interaction. We
      show that Plk1 associates with TRF1, and Plk1 phosphorylates TRF1 at Ser-435 in
      vivo. Moreover, Cdk1, serving as a priming kinase, phosphorylates TRF1 to
      generate a docking site for Plk1 toward TRF1. In the presence of nocodazole,
      ectopic expression of wild type TRF1 but not TRF1 with alanine mutation in the
      Plk1 phosphorylation site induces apoptosis in cells containing short telomeres
      but not in cells containing long telomeres. Unexpectedly, down-regulation of TRF1
      by RNA interference affects cell proliferation and results in obvious apoptosis
      in cells with short telomeres but not in cells with long telomeres. Importantly,
      we observe that telomeric DNA binding ability of TRF1 is cell cycle-regulated and
      reaches a peak during mitosis. Upon phosphorylation by Plk1 in vivo and in vitro,
      the ability of TRF1 to bind telomeric DNA is dramatically increased. These
      results demonstrate that Plk1 interacts with and phosphorylates TRF1 and suggest
      that Plk1-mediated phosphorylation is involved in both TRF1 overexpression
      induced apoptosis and its telomeric DNA binding ability.

PMID- 18625708
TI  - Interaction studies and alanine scanning analysis of a semi-synthetic split
      intein reveal thiazoline ring formation from an intermediate of the protein
      splicing reaction.
AB  - We recently reported an artificially split intein based on the Ssp DnaB mini
      intein that consists of a synthetic N-terminal intein fragment (Int(N)) and a
      recombinant C-terminal part (Int(C)), which are 11 and 143 amino acids in length,
      respectively. This intein holds great promise for the preparation of semi
      synthetic proteins by protein trans-splicing. In this work we synthesized a set
      of Int(N) peptide variants to investigate their structure-function relationship
      with regard to fragment association and promotion of protein trans-splicing. A
      further truncation of the Int(N) sequence below 11 amino acids resulted in loss
      of activity, whereas C-terminal extensions were tolerated. Alanine scanning
      analysis identified three essential hydrophobic residues, whereas substitutions
      at other positions were tolerated. We developed assays to monitor association of
      Int(N) with an Int(C) mutant blocked in protein splicing by native PAGE and
      fluorescence anisotropy. The kinetic parameters of intein complex formation were
      K(d) = 1.1 mum, k(on) = 16.8 m(-1) s(-1), and k(off) = 1.8 x 10(-5) s(-1) for the
      native Int(N11) sequence. Intriguingly, a G(-1)A substitution, previously known
      to significantly impair protein splicing, was revealed to result in thiazoline
      ring formation involving the catalytic Cys-1, likely by aberrant dehydration of a
      oxythiazolidine intermediate. This finding provides experimental evidence for the
      postulated intermediate during the initial N/S acyl shift and underlines the
      delicate spatial and temporal alignment required in the intein active site to
      prevent side reactions of the protein-splicing pathway.

PMID- 18625709
TI  - ATR-dependent activation of p38 MAP kinase is responsible for apoptotic cell
      death in cells depleted of Cdc7.
AB  - Cdc7 is a serine/threonine kinase that plays essential roles in the initiation of
      eukaryotic DNA replication and checkpoint response. In previous studies,
      depletion of Cdc7 by small interfering RNA was shown to induce an abortive S
      phase that led to the cell cycle arrest in normal human fibroblasts and apoptotic
      cell death in various cancer cells. Here we report that stress-activated p38 MAP
      kinase was activated and responsible for apoptotic cell death in Cdc7-depleted
      HeLa cells. The activation of p38 MAP kinase in the Cdc7-depleted cells was shown
      to depend on ATR, a major sensor kinase for checkpoint or DNA damage responses.
      Only the p38 MAP kinase, and not the other stress-activated kinases such as JNK
      or ERK, was activated, and both caspase 8 and caspase 9 were activated for the
      induction of apoptosis. Activation of apoptosis in Cdc7-depleted cells was
      completely abolished in cells treated with small interfering RNA or an inhibitor
      of the p38 MAP kinase, suggesting that p38 MAP kinase activation was responsible
      for apoptotic cell death. Taken together, we suggest that the ATR-dependent
      activation of the p38 MAP kinase is a major signaling pathway that induces
      apoptotic cell death after depletion of Cdc7 in cancer cells.

PMID- 18625710
TI  - The role of Kalirin9 in p75/nogo receptor-mediated RhoA activation in cerebellar
      granule neurons.
AB  - p75 and the Nogo receptor form a signaling unit for myelin inhibitory molecules,
      with p75 being responsible for RhoA activation. Because p75 lacks the GDP/GTP
      exchange factor domain, it has remained unclear how p75 activates RhoA. Here, we
      report that Kalirin9, a dual RhoGEF, binds p75 directly and regulates p75-Nogo
      receptor-dependent RhoA activation and neurite inhibition in response to myelin
      associated glycoprotein. The region of p75 that Kalirin9 binds includes its
      mastoparan-like fifth helix, which was shown to recruit RhoGDI-RhoA. As predicted
      from the presence of a shared binding site, we found that Kalirin9 competes with
      RhoGDI for p75 binding in a dose-dependent manner in vitro. In line with these
      data, myelin-associated glycoprotein addition to cerebellar granule neurons
      resulted in a reduction in the association of Kalirin9 with p75, and a
      simultaneous increase in the binding of RhoGDI to p75. These results reveal a
      mechanism by which the fifth helix of p75 regulates RhoA activation.

PMID- 18625711
TI  - Calcium binds to leptospiral immunoglobulin-like protein, LigB, and modulates
      fibronectin binding.
AB  - Pathogenic Leptospira spp. express immunoglobulin-like proteins, LigA and LigB,
      which serve as adhesins to bind to extracellular matrices and mediate their
      attachment on host cells. However, nothing is known about the mechanism by which
      these proteins are involved in pathogenesis. We demonstrate that LigBCen2 binds
      Ca(2+), as evidenced by inductively coupled plasma optical emission spectrometry,
      energy dispersive spectrometry, (45)Ca overlay, and mass spectrometry, although
      there is no known motif for Ca(2+) binding. LigBCen2 binds four Ca(2+) as
      determined by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry. The dissociation constant, K(D), for Ca(2+) binding is 7 mum, as
      measured by isothermal titration calorimetry and calcium competition experiments.
      The nature of the Ca(2+)-binding site in LigB is possibly similar to that seen in
      the betagamma-crystallin superfamily, since structurally, both families of
      proteins possess the Greek key type fold. The conformation of LigBCen2 was
      significantly influenced by Ca(2+) binding as shown by far- and near-UV CD and by
      fluorescence spectroscopy. In the apo form, the protein appears to be partially
      unfolded, as seen in the far-UV CD spectrum, and upon Ca(2+) binding, the protein
      acquires significant beta-sheet conformation. Ca(2+) binding stabilizes the
      protein as monitored by thermal unfolding by CD (50.7-54.8 degrees C) and by
      differential scanning calorimetry (50.0-55.7 degrees C). Ca(2+) significantly
      assists the binding of LigBCen2 to the N-terminal domain of fibronectin and
      perturbs the secondary structure, suggesting the involvement of Ca(2+) in
      adhesion. We demonstrate that LigB is a novel bacterial Ca(2+)-binding protein
      and suggest that Ca(2+) binding plays a pivotal role in the pathogenesis of
      leptospirosis.

PMID- 18625712
TI  - Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in
      gastric parietal cells.
AB  - Helicobacter pylori persistently colonize the human stomach and have been linked
      to atrophic gastritis and gastric carcinoma. Although it is well known that H.
      pylori infection can result in hypochlorhydria, the molecular mechanisms
      underlying this phenomenon remain poorly understood. Here we show that VacA
      permeabilizes the apical membrane of gastric parietal cells and induces
      hypochlorhydria. The functional consequences of VacA infection on parietal cell
      physiology were studied using freshly isolated rabbit gastric glands and cultured
      parietal cells. Secretory activity of parietal cells was judged by an aminopyrine
      uptake assay and confocal microscopic examination. VacA permeabilization induces
      an influx of extracellular calcium, followed by activation of calpain and
      subsequent proteolysis of ezrin at Met(469)-Thr(470), which results in the
      liberation of ezrin from the apical membrane of the parietal cells. VacA
      treatment inhibits acid secretion by preventing the recruitment of H,K-ATPase
      containing tubulovesicles to the apical membrane of gastric parietal cells.
      Electron microscopic examination revealed that VacA treatment disrupts the radial
      arrangement of actin filaments in apical microvilli due to the loss of ezrin
      integrity in parietal cells. Significantly, expression of calpain-resistant ezrin
      restored the functional activity of parietal cells in the presence of VacA.
      Proteolysis of ezrin in VacA-infected parietal cells is a novel mechanism
      underlying H. pylori-induced inhibition of acid secretion. Our results indicate
      that VacA disrupts the apical membrane-cytoskeletal interactions in gastric
      parietal cells and thereby causes hypochlorhydria.

PMID- 18625713
TI  - Deficiency in microfibril-associated glycoprotein-1 leads to complex phenotypes
      in multiple organ systems.
AB  - Microfibril-associated glycoprotein-1 (MAGP-1) is a small molecular weight
      component of the fibrillin-rich microfibril. Gene-targeted inactivation of MAGP-1
      reveals a complex phenotype that includes increased body weight and size due to
      excess body fat, an altered wound healing response in bone and skin, and a
      bleeding diathesis. Elastic tissues rich in MAGP-1-containing microfibrils
      develop normally and show normal function. The penetrance of MAGP-1-null
      phenotypes is highly variable and mouse strain-dependent, suggesting the
      influence of modifier genes. MAGP-1 was found to bind active transforming growth
      factor-beta (TGF-beta) and BMP-7 with high affinity, suggesting that it may be an
      important modulator of microfibril-mediated growth factor signaling. Many of the
      phenotypic traits observed in MAGP-1-deficient mice are consistent with loss of
      TGF-beta function and are generally opposite those associated with mutations in
      fibrillin-1 that result in enhanced TGF-beta signaling. Increased body size and
      fat deposition in MAGP-1-mutant animals are particularly intriguing given the
      localization of obesity traits in humans to the region on chromosome 1 containing
      the MAGP-1 gene.

PMID- 18625714
TI  - Phosphorylation of MUC1 by Met modulates interaction with p53 and MMP1
      expression.
AB  - MUC1, a transmembrane mucin, is a key modulator of several signaling pathways
      that affect oncogenesis, motility, and cell morphology. The interaction of MUC1
      cytoplasmic tail (MUC1CT) with signal transducers and its nuclear translocation
      and subsequent biological responses are believed to be regulated by
      phosphorylation status, but the precise mechanisms by which this occurs remain
      poorly defined. We detected a novel association between the Met receptor tyrosine
      kinase and the MUC1CT. Met catalyzed phosphorylation of tyrosine at YHPM in the
      MUC1CT. Stimulation of S2-013.MUC1F pancreatic cancer cells with hepatocyte
      growth factor facilitated nuclear localization of MUC1CT, as determined by real
      time confocal imaging analysis. MUC1 overexpression also facilitated faster
      turnover of Met. Phosphorylation of MUC1CT by Met enhanced its interaction with
      p53, which led to suppression of AP1 transcription factor activity through
      interactions at the MMP1 promoter, ultimately leading to reduced transcription of
      MMP1. This correlated with a decrease in hepatocyte growth factor-induced
      invasiveness when MUC1 was overexpressed. The results demonstrate that MUC1
      modulates Met-mediated oncogenic signaling in cancer.

PMID- 18625715
TI  - Importance of the cyanobacterial Gun4 protein for chlorophyll metabolism and
      assembly of photosynthetic complexes.
AB  - Gun4 is a porphyrin-binding protein that activates magnesium chelatase, a
      multimeric enzyme catalyzing the first committed step in chlorophyll
      biosynthesis. In plants, GUN4 has been implicated in plastid-to-nucleus
      retrograde signaling processes that coordinate both photosystem II and
      photosystem I nuclear gene expression with chloroplast function. In this work we
      present the functional analysis of Gun4 from the cyanobacterium Synechocystis sp.
      PCC 6803. Affinity co-purification of the FLAG-tagged Gun4 with the ChlH subunit
      of the magnesium chelatase confirmed the association of Gun4 with the enzyme in
      cyanobacteria. Inactivation of the gun4 gene abolished photoautotrophic growth of
      the resulting gun4 mutant strain that exhibited a decreased activity of magnesium
      chelatase. Consequently, the cellular content of chlorophyll-binding proteins was
      highly inadequate, especially that of proteins of photosystem II. Immunoblot
      analyses, blue native polyacrylamide gel electrophoresis, and radiolabeling of
      the membrane protein complexes suggested that the availability of the photosystem
      II antenna protein CP47 is a limiting factor for the photosystem II assembly in
      the gun4 mutant.

PMID- 18625716
TI  - Runx2 regulates G protein-coupled signaling pathways to control growth of
      osteoblast progenitors.
AB  - Runt-related transcription factor 2 (Runx2) controls lineage commitment,
      proliferation, and anabolic functions of osteoblasts as the subnuclear effector
      of multiple signaling axes (e.g. transforming growth factor-beta/BMP-SMAD,
      SRC/YES-YAP, and GROUCHO/TLE). Runx2 levels oscillate during the osteoblast cell
      cycle with maximal levels in G(1). Here we examined what functions and target
      genes of Runx2 control osteoblast growth. Forced expression of wild type Runx2
      suppresses growth of Runx2(-/-) osteoprogenitors. Point mutants defective for
      binding to WW domain or SMAD proteins or the nuclear matrix retain this growth
      regulatory ability. Hence, key signaling pathways are dispensable for growth
      control by Runx2. However, mutants defective for DNA binding or C-terminal gene
      repression/activation functions do not block proliferation. Target gene analysis
      by Affymetrix expression profiling shows that the C terminus of Runx2 regulates
      genes involved in G protein-coupled receptor signaling (e.g. Rgs2, Rgs4, Rgs5,
      Rgs16, Gpr23, Gpr30, Gpr54, Gpr64, and Gna13). We further examined the function
      of two genes linked to cAMP signaling as follows: Gpr30 that is stimulated and
      Rgs2 that is down-regulated by Runx2. RNA interference of Gpr30 and forced
      expression of Rgs2 in each case inhibit osteoblast proliferation. Notwithstanding
      its growth-suppressive potential, our results surprisingly indicate that Runx2
      may sensitize cAMP-related G protein-coupled receptor signaling by activating
      Gpr30 and repressing Rgs2 gene expression in osteoblasts to increase
      responsiveness to mitogenic signals.

PMID- 18625717
TI  - No overt nucleosome eviction at deprotected telomeres.
AB  - Dysfunctional telomeres elicit the canonical DNA damage response, which includes
      the activation of the ATM or ATR kinase signaling pathways and end processing by
      nonhomologous end joining (NHEJ) or homologous recombination (HR). The cellular
      response to DNA double-strand breaks has been proposed to involve chromatin
      remodeling and nucleosome eviction, but whether dysfunctional telomeres undergo
      chromatin reorganization is not known. Here, we report on the nucleosomal
      organization of telomeres that have become deprotected through the deletion of
      the shelterin components TRF2 or POT1. We found no evidence of changes in the
      nucleosomal organization of the telomeric chromatin or nucleosome eviction near
      the telomere terminus. An unaltered chromatin structure was observed at telomeres
      lacking TRF2, which activate the ATM kinase and are a substrate for NHEJ.
      Similarly, telomeres lacking POT1a and POT1b, which activate the ATR kinase,
      showed no overt nucleosome eviction. Finally, telomeres lacking TRF2 and Ku70,
      which are processed by HR, appeared to maintain their original nucleosomal
      organization. We conclude that ATM signaling, ATR signaling, NHEJ, and HR at
      deprotected telomeres can take place in the absence of overt nucleosome eviction.

PMID- 18625718
TI  - Genome analysis identifies the p15ink4b tumor suppressor as a direct target of
      the ZNF217/CoREST complex.
AB  - The ZNF217 oncoprotein is a constituent of a core transcriptional complex that
      includes CoREST, histone deacetylase 1/2, lysine demethylase 1, and the C
      terminal binding protein 1/2. We have combined genome-wide expression profiling
      and chromatin immunoprecipitation with directed selection and ligation (ChIP-DSL)
      to identify a subset of genes directly regulated by ZNF217. Our results establish
      p15(ink4b) as a direct target of the ZNF217 complex. Downregulation of ZNF217 in
      MCF-7 breast cancer cells resulted in a dramatic increase in p15(ink4b)
      expression and coincided with increases in dimethylation of H3-K4 and,
      surprisingly, a decrease in K9/K14-H3 acetylation. Stimulation of HaCaT cells
      with transforming growth factor beta (TGF-beta) resulted in a release of ZNF217
      and a concomitant binding of SMAD2 to the proximal promoter, which preceded
      increases in ink4b protein expression. Furthermore, the changes in chromatin
      marks at the p15(ink4b) promoter following TGF-beta stimulation were similar to
      those observed following ZNF217 downregulation. Collectively, these results
      establish the ZNF217 complex as a novel negative regulator of the p15(ink4b) gene
      and may constitute an important link between amplification of ZNF217 and the loss
      of TGF-beta responsiveness in breast cancer.

PMID- 18625719
TI  - Xist RNA is confined to the nuclear territory of the silenced X chromosome
      throughout the cell cycle.
AB  - In mammalian female cells, one X chromosome is inactivated to prevent a dose
      difference in the expression of X-encoded proteins between males and females.
      Xist RNA, required for X chromosome inactivation, is transcribed from the future
      inactivated X chromosome (Xi), where it spreads in cis, to initiate silencing. We
      have analyzed Xist RNA transcription and localization throughout the cell cycle.
      It was found that Xist transcription is constant and that the mature RNA remains
      attached to the Xi throughout mitosis. Diploid and tetraploid cell lines with an
      MS2-tagged Xist gene were used to investigate spreading of Xist. Most XXXX(MS2)
      tetraploid mouse embryonic stem (ES) cells inactivate the X(MS2) chromosome and
      one other X chromosome. Analysis of cells with two Xi's indicates that Xist RNA
      is retained by the Xi of its origin and does not spread in trans. Also, in
      XX(MS2) diploid mouse ES cells with an autosomal Xist transgene, there is no
      trans exchange of Xist RNA from the Xi to the autosome. We propose that Xist RNA
      does not dissociate from the Xi of its origin, which precludes a model of
      diffusion-mediated trans spreading of Xist RNA.

PMID- 18625720
TI  - Cyclin-dependent kinase-associated proteins Cks1 and Cks2 are essential during
      early embryogenesis and for cell cycle progression in somatic cells.
AB  - Cks proteins associate with cyclin-dependent kinases and have therefore been
      assumed to play a direct role in cell cycle regulation. Mammals have two
      paralogs, Cks1 and Cks2, and individually deleting the gene encoding either in
      the mouse has previously been shown not to impact viability. In this study we
      show that simultaneously disrupting CKS1 and CKS2 leads to embryonic lethality,
      with embryos dying at or before the morula stage after only two to four cell
      division cycles. RNA interference (RNAi)-mediated silencing of CKS genes in mouse
      embryonic fibroblasts (MEFs) or HeLa cells causes cessation of proliferation. In
      MEFs CKS silencing leads to cell cycle arrest in G(2), followed by rereplication
      and polyploidy. This phenotype can be attributed to impaired transcription of the
      CCNB1, CCNA2, and CDK1 genes, encoding cyclin B1, cyclin A, and Cdk1,
      respectively. Restoration of cyclin B1 expression rescues the cell cycle arrest
      phenotype conferred by RNAi-mediated Cks protein depletion. Consistent with a
      direct role in transcription, Cks2 is recruited to chromatin in general and to
      the promoter regions and open reading frames of genes requiring Cks function with
      a cell cycle periodicity that correlates with their transcription.

PMID- 18625721
TI  - Retinoic acid utilizes CREB and USF1 in a transcriptional feed-forward loop in
      order to stimulate MKP1 expression in human immunodeficiency virus-infected
      podocytes.
AB  - Nef-induced podocyte proliferation and dedifferentiation via mitogen-activated
      protein kinase 1,2 (MAPK1,2) activation plays a role in human immunodeficiency
      virus (HIV) nephropathy pathogenesis. All-trans retinoic acid (atRA) reverses the
      HIV-induced podocyte phenotype by activating cyclic AMP (cAMP)/protein kinase A
      (PKA) and inhibiting MAPK1,2. Here we show that atRA, through cAMP and PKA,
      triggers a feed-forward loop involving CREB and USF1 to induce biphasic
      stimulation of MKP1. atRA stimulated CREB and USF1 binding to the MKP1 gene
      promoter, as shown by gel shifting and chromatin immunoprecipitation assays. CREB
      directly mediated the early phase of atRA-induced MKP1 stimulation; whereas the
      later phase was mediated by CREB indirectly through induction of USF1. These
      findings were confirmed by a reporter gene assay using the MKP1 promoter with
      mutation of CRE or Ebox binding sites. Consistent with these findings, the
      biological effects of atRA on podocytes were inhibited by silencing either MKP1,
      CREB, or USF1 with small interfering RNA. atRA also induced CREB phosphorylation
      and MKP1 expression and reduced MAPK1,2 phosphorylation in kidneys of HIV type 1
      infected transgenic mice. We conclude that atRA induces sustained activation of
      MKP1 to suppress Nef-induced activation of the Src-MAPK1,2 pathway, thus
      returning the podocyte to a more differentiated state. The mechanism involves a
      feed-forward loop where activation of one transcription factor (TF) (CREB) leads
      to induction of a second TF (USF1).

PMID- 18625722
TI  - Histone deacetylase 7 promotes PML sumoylation and is essential for PML nuclear
      body formation.
AB  - Promyelocytic leukemia protein (PML) sumoylation has been proposed to control the
      formation of PML nuclear bodies (NBs) and is crucial for PML-dependent cellular
      processes, including apoptosis and transcriptional regulation. However, the
      regulatory mechanisms of PML sumoylation and its specific roles in the formation
      of PML NBs remain largely unknown. Here, we show that histone deacetylase 7
      (HDAC7) knockdown reduces the size and the number of the PML NBs in human
      umbilical vein endothelial cells (HUVECs). HDAC7 coexpression stimulates PML
      sumoylation independent of its HDAC activity. Furthermore, HDAC7 associates with
      the E2 SUMO ligase, Ubc9, and stimulates PML sumoylation in vitro, suggesting
      that it possesses a SUMO E3 ligase-like activity to promote PML sumoylation.
      Importantly, HDAC7 knockdown inhibits tumor necrosis factor alpha-induced PML
      sumoylation and the formation of PML NBs in HUVECs. These results demonstrate a
      novel function of HDAC7 and provide a regulatory mechanism of PML sumoylation.

PMID- 18625723
TI  - A novel Tel1/ATM N-terminal motif, TAN, is essential for telomere length
      maintenance and a DNA damage response.
AB  - Tel1/ATM, a conserved phosphatidylinositol 3-kinase-related kinase (PIKK), acts
      in the response to DNA damage and regulates telomere maintenance. PIKK family
      members share an extended N-terminal region of low sequence homology. Sequence
      alignment of the N terminus of Tel1/ATM orthologs revealed a conserved, novel
      motif we term TAN (for Tel1/ATM N-terminal motif). Point mutations in conserved
      residues of the TAN motif resulted in telomere shortening, and its deletion
      caused the same short telomere phenotype as complete deletion of Tel1 did.
      Overexpressing Tel1 TAN mutants did not rescue telomere shortening. The TAN motif
      was also essential for the function of Tel1 in the response to DNA damage, as TAN
      deleted Tel1 was indistinguishable from the complete lack of Tel1 in causing
      reduced viability and signaling through Rad53 upon DNA damage. Strikingly, TAN
      deletion reduced recruitment of Tel1 to a double-strand DNA break. Together,
      these results define a conserved sequence motif within an otherwise poorly
      defined region of the Tel1/ATM kinase family proteins that is essential for
      normal Tel1 function in Saccharomyces cerevisiae.

PMID- 18625724
TI  - Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S
      protein biogenesis.
AB  - In a forward genetic screen for interaction with mitochondrial iron carrier
      proteins in Saccharomyces cerevisiae, a hypomorphic mutation of the essential
      DRE2 gene was found to confer lethality when combined with Delta mrs3 and Delta
      mrs4. The dre2 mutant or Dre2-depleted cells were deficient in cytosolic Fe/S
      cluster protein activities while maintaining mitochondrial Fe/S clusters. The
      Dre2 amino acid sequence was evolutionarily conserved, and cysteine motifs
      (CX(2)CXC and twin CX(2)C) in human and yeast proteins were perfectly aligned.
      The human Dre2 homolog (implicated in blocking apoptosis and called CIAPIN1 or
      anamorsin) was able to complement the nonviability of a Deltadre2 deletion
      strain. The Dre2 protein with triple hemagglutinin tag was located in the
      cytoplasm and in the mitochondrial intermembrane space. Yeast Dre2 overexpressed
      and purified from bacteria was brown and exhibited signature absorption and
      electron paramagnetic resonance spectra, indicating the presence of both [2Fe-2S]
      and [4Fe-4S] clusters. Thus, Dre2 is an essential conserved Fe/S cluster protein
      implicated in extramitochondrial Fe/S cluster assembly, similar to other
      components of the so-called CIA (cytoplasmic Fe/S cluster assembly) pathway
      although partially localized to the mitochondrial intermembrane space.

PMID- 18625725
TI  - Transforming growth factor beta engages TACE and ErbB3 to activate
      phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and
      desensitizes cells to trastuzumab.
AB  - In HER2-overexpressing mammary epithelial cells, transforming growth factor beta
      (TGF-beta) activated phosphatidylinositol-3 kinase (PI3K)/Akt and enhanced
      survival and migration. Treatment with TGF-beta or expression of an activated TGF
      beta type I receptor (Alk5 with the mutation T204D [Alk5(T204D)]) induced
      phosphorylation of TACE/ADAM17 and its translocation to the cell surface,
      resulting in increased secretion of TGF-alpha, amphiregulin, and heregulin. In
      turn, these ligands enhanced the association of p85 with ErbB3 and activated
      PI3K/Akt. RNA interference of TACE or ErbB3 prevented TGF-beta-induced activation
      of Akt and cell invasiveness. Treatment with TGF-beta or expression of
      Alk5(T204D) in HER2-overexpressing cells reduced their sensitivity to the HER2
      antibody trastuzumab. Inhibition of Alk5, PI3K, TACE, or ErbB3 restored
      sensitivity to trastuzumab. A gene signature induced by Alk5(T204D) expression
      correlated with poor clinical outcomes in patients with invasive breast cancer.
      These results suggest that by acting on ErbB ligand shedding, an excess of TGF
      beta may result in (i) conditioning of the tumor microenvironment with growth
      factors that can engage adjacent stromal and endothelial cells; (ii) potentiation
      of signaling downstream ErbB receptors, thus contributing to tumor progression
      and resistance to anti-HER2 therapies; and (iii) poor clinical outcomes in women
      with breast cancer.

PMID- 18625726
TI  - Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and
      together with Rap1b controls human endothelial cell functions.
AB  - Angiogenesis, the formation of new blood vessels from existing vasculature, is
      regulated primarily by endothelial cell activity. We show herein that the Ras
      family GTPase Rap1 has a key role in the regulation of angiogenesis by modulating
      endothelial cell functions. Blood vessel growth into fibroblast growth factor 2
      (FGF2)-containing Matrigel plugs was absent from rap1a(-/-) mice, and aortic
      rings derived from rap1a(-/-) mice failed to sprout primitive tubes in response
      to FGF2, when the tissue was embedded in Matrigel. Knocking down either rap1a or
      rap1b, two closely related rap1 family members, in human microvascular
      endothelial cells (HMVECs) by utilizing siRNA confirmed that Rap1 plays key roles
      in endothelial cell function. The rap1a or rap1b knockdown resulted in decreased
      adhesion to extracellular matrices and impaired cell migration. HMVEC monolayers
      lacking Rap1 had increased permeability, and Rap1-deficient endothelial cells
      failed to form three-dimensional tubular structures when they were plated on
      Matrigel in vitro. Finally, the activation levels of extracellular signal
      regulated kinase (ERK), p38, and Rac, which are important signaling molecules in
      angiogenesis, were all reduced in response to FGF2 when either of the Rap1
      proteins was depleted. These observations place Rap1 centrally in the human
      angiogenic process and suggest that both the Rap1a and Rap1b proteins are
      required for angiogenesis and that Rap1 is a critical mediator of FGF-induced ERK
      activation.

PMID- 18625727
TI  - A unique protection signal in Cubitus interruptus prevents its complete
      proteasomal degradation.
AB  - The limited proteolysis of Cubitus interruptus (Ci), the transcription factor for
      the developmentally and medically important Hedgehog (Hh) signaling pathway,
      triggers a critical switch between transcriptional repressor and activator forms.
      Ci repressor is formed when the C terminus of full-length Ci is degraded by the
      ubiquitin-proteasome pathway, an unusual reaction since the proteasome typically
      completely degrades its substrates. We show that several regions of Ci are
      required for generation of the repressor form: the zinc finger DNA binding
      domain, a single lysine residue (K750) near the degradation end point, and a 163
      amino-acid region at the C terminus. Unlike other proteins that are partially
      degraded by the proteasome, dimerization is not a key feature of Ci processing.
      Using a pulse-chase assay in cultured Drosophila cells, we distinguish between
      regions required for initiation of degradation and those required for the
      protection of the Ci N terminus from degradation. We present a model whereby the
      zinc finger region and K750 together form a unique protection signal that
      prevents the complete degradation of Ci by the proteasome.

PMID- 18625728
TI  - The protein kinase C-responsive inhibitory domain of CARD11 functions in NF
      kappaB activation to regulate the association of multiple signaling cofactors
      that differentially depend on Bcl10 and MALT1 for association.
AB  - The activation of NF-kappaB by T-cell receptor (TCR) signaling is critical for T
      cell activation during the adaptive immune response. CARD11 is a multidomain
      adapter that is required for TCR signaling to the IkappaB kinase (IKK) complex.
      During TCR signaling, the region in CARD11 between the coiled-coil and PDZ
      domains is phosphorylated by protein kinase Ctheta (PKCtheta) in a required step
      in NF-kappaB activation. In this report, we demonstrate that this region
      functions as an inhibitory domain (ID) that controls the association of CARD11
      with multiple signaling cofactors, including Bcl10, TRAF6, TAK1, IKKgamma, and
      caspase-8, through an interaction that requires both the caspase recruitment
      domain (CARD) and the coiled-coil domain. Consistent with the ID-mediated control
      of their association, we demonstrate that TRAF6 and caspase-8 associate with
      CARD11 in T cells in a signal-inducible manner. Using an RNA interference rescue
      assay, we demonstrate that the CARD, linker 1, coiled-coil, linker 3, SH3, linker
      4, and GUK domains are each required for TCR signaling to NF-kappaB downstream of
      ID neutralization. Requirements for the CARD, linker 1, and coiled-coil domains
      in signaling are consistent with their roles in the association of CARD11 with
      Bcl10, TRAF6, TAK1, caspase-8, and IKKgamma. Using Bcl10- and MALT1-deficient
      cells, we show that CARD11 can recruit signaling cofactors independently of one
      another in a signal-inducible manner.

PMID- 18625729
TI  - Salmonella enterica serovar Typhimurium NiFe uptake-type hydrogenases are
      differentially expressed in vivo.
AB  - Salmonella enterica serovar Typhimurium, a common enteric pathogen, possesses
      three NiFe uptake-type hydrogenases. The results from mouse infection studies
      suggest that the H(2) oxidation capacity provided by these hydrogenases is
      important for virulence. Since the three enzymes are similar in structure and
      function, it may be expected that they are utilized under different locations and
      times during an infection. A recombination-based method to examine promoter
      activity in vivo (RIVET) was used to determine hydrogenase gene expression in
      macrophages, polymorphonuclear leukocyte (PMN)-like cells, and a mouse model of
      salmonellosis. The hyd and hya promoters showed increased expression in both
      murine macrophages and human PMN-like cells compared to that in the medium-only
      controls. Quantitative reverse transcription-PCR results suggested that hyb is
      also expressed in phagocytes. A nonpolar hya mutant was compromised for survival
      in macrophages compared to the wild type. This may be due to lower tolerance to
      acid stress, since the hya mutant was much more acid sensitive than the wild
      type. In addition, hya mutant cells were internalized by macrophages the same as
      wild-type cells. Mouse studies (RIVET) indicate that hyd is highly expressed in
      the liver and spleen early during infection but is expressed poorly in the ileum
      in infected animals. Late in the infection, the hyd genes were expressed at high
      levels in the ileum as well as in the liver and spleen. The hya genes were
      expressed at low levels in all locations tested. These results suggest that the
      hydrogenases are used to oxidize hydrogen in different stages of an infection.

PMID- 18625730
TI  - Effects of Clostridium perfringens beta-toxin on the rabbit small intestine and
      colon.
AB  - Clostridium perfringens type B and type C isolates, which produce beta-toxin
      (CPB), cause fatal diseases originating in the intestines of humans or livestock.
      Our previous studies demonstrated that CPB is necessary for type C isolate CN3685
      to cause bloody necrotic enteritis in a rabbit ileal loop model and also showed
      that purified CPB, in the presence of trypsin inhibitor (TI), can reproduce type
      C pathology in rabbit ileal loops. We report here a more complete
      characterization of the effects of purified CPB in the rabbit small and large
      intestines. One microgram of purified CPB, in the presence of TI, was found to be
      sufficient to cause significant accumulation of hemorrhagic luminal fluid in
      duodenal, jejunal, or ileal loops treated for 6 h with purified CPB, while no
      damage was observed in corresponding loops receiving CPB (no TI) or TI alone. In
      contrast to the CPB sensitivity of the small intestine, the colon was not
      affected by 6 h of treatment with even 90 mug of purified CPB whether or not TI
      was present. Time course studies showed that purified CPB begins to induce small
      intestinal damage within 1 h, at which time the duodenum is less damaged than the
      jejunum or ileum. These observations help to explain why type B and C infections
      primarily involve the small intestine, establish CPB as a very potent and fast
      acting toxin in the small intestines, and confirm a key role for intestinal
      trypsin as an innate intestinal defense mechanism against CPB-producing C.
      perfringens isolates.

PMID- 18625731
TI  - Vaccination with heat shock protein 60 induces a protective immune response
      against experimental Paracoccidioides brasiliensis pulmonary infection.
AB  - Paracoccidioides brasiliensis causes a chronic granulomatous mycosis prevalent in
      Latin America. The successful resolution of infection with this fungus is
      dependent on the activation of cellular immunity. We previously identified heat
      shock protein 60 (HSP60) as a target of the humoral response in
      paracoccidioidomycosis. Herein we expressed the gene encoding HSP60 in
      Escherichia coli and analyzed the immunological activity of this recombinant
      antigen. The immunization of BALB/c mice with recombinant protein emulsified in
      adjuvant stimulated a cellular immune response. Splenocytes from immunized mice
      proliferated in response to antigen and released interleukin-12 and gamma
      interferon (IFN-gamma). Vaccination with HSP60 reduced the fungal burden in mice
      given 10(6) or 10(7) yeasts and protected mice from a lethal challenge. The
      efficacy of the vaccination was blunted by the neutralization of IFN-gamma.
      CD4(+) cells were necessary for the efficacy of the vaccination in both the
      afferent and efferent phases. Thus, we have demonstrated that this immunodominant
      antigen is a candidate for the development of a vaccine against this fungus.

PMID- 18625732
TI  - The commensal Streptococcus salivarius K12 downregulates the innate immune
      responses of human epithelial cells and promotes host-microbe homeostasis.
AB  - Streptococcus salivarius is an early colonizer of human oral and nasopharyngeal
      epithelia, and strain K12 has reported probiotic effects. An emerging paradigm
      indicates that commensal bacteria downregulate immune responses through the
      action on NF-kappaB signaling pathways, but additional mechanisms underlying
      probiotic actions are not well understood. Our objective here was to identify
      host genes specifically targeted by K12 by comparing their responses with
      responses elicited by pathogens and to determine if S. salivarius modulates
      epithelial cell immune responses. RNA was extracted from human bronchial
      epithelial cells (16HBE14O- cells) cocultured with K12 or bacterial pathogens.
      cDNA was hybridized to a human 21K oligonucleotide-based array. Data were
      analyzed using ArrayPipe, InnateDB, PANTHER, and oPOSSUM. Interleukin 8 (IL-8)
      and growth-regulated oncogene alpha (Groalpha) secretion were determined by
      enzyme-linked immunosorbent assay. It was demonstrated that S. salivarius K12
      specifically altered the expression of 565 host genes, particularly those
      involved in multiple innate defense pathways, general epithelial cell function
      and homeostasis, cytoskeletal remodeling, cell development and migration, and
      signaling pathways. It inhibited baseline IL-8 secretion and IL-8 responses to LL
      37, Pseudomonas aeruginosa, and flagellin in epithelial cells and attenuated
      Groalpha secretion in response to flagellin. Immunosuppression was coincident
      with the inhibition of activation of the NF-kappaB pathway. Thus, the commensal
      and probiotic behaviors of S. salivarius K12 are proposed to be due to the
      organism (i) eliciting no proinflammatory response, (ii) stimulating an anti
      inflammatory response, and (iii) modulating genes associated with adhesion to the
      epithelial layer and homeostasis. S. salivarius K12 might thereby ensure that it
      is tolerated by the host and maintained on the epithelial surface while actively
      protecting the host from inflammation and apoptosis induced by pathogens.

PMID- 18625733
TI  - Analysis of PRA1 and its relationship to Candida albicans- macrophage
      interactions.
AB  - Phagocytosis of Candida albicans by either primary bone marrow-derived mouse
      macrophages or RAW 264.7 cells upregulated transcription of PRA1, which encodes a
      cell wall/membrane-associated antigen previously described as a fibrinogen
      binding protein. However, a pra1 null mutant was still able to bind fibrinogen,
      showing that Pra1p is not uniquely required for fibrinogen binding. As well, Pra1
      tagged with green fluorescent protein did not colocalize with AlexaFluor 546
      labeled human fibrinogen, and while PRA1 expression was inhibited when Candida
      was grown in fetal bovine serum-containing medium, Candida binding to fibrinogen
      was activated by these conditions. Therefore, it appears that Pra1p can play at
      most a minor role in fibrinogen binding to C. albicans. PRA1 gene expression is
      induced in vitro by alkaline pH, and therefore its activation in phagosomes
      suggested that phagosome maturation was suppressed by the presence of Candida
      cells. LysoTracker red-labeled organelles failed to fuse with phagosomes
      containing live Candida, while phagosomes containing dead Candida underwent a
      normal phagosome-to-phagolysosome maturation. Immunofluorescence staining with
      the early/recycling endosomal marker transferrin receptor (CD71) suggested that
      live Candida may escape macrophage destruction through the inhibition of
      phagolysosomal maturation.

PMID- 18625734
TI  - Outer membrane antigens of the uropathogen Proteus mirabilis recognized by the
      humoral response during experimental murine urinary tract infection.
AB  - Proteus mirabilis, a gram-negative bacterium, is a frequent cause of complicated
      urinary tract infections in those with functional or anatomical abnormalities or
      those subject to long-term catheterization. To systematically identify surface
      exposed antigens as potential vaccine candidates, proteins in the outer membrane
      fraction of bacteria were separated by two-dimensional gel electrophoresis and
      subjected to Western blotting with sera from mice experimentally infected with P.
      mirabilis. Protein spots reactive with sera were identified by mass spectrometry,
      which in conjunction with the newly completed genome sequence of P. mirabilis
      HI4320, was used to identify surface-exposed antigens. Culture conditions that
      may mimic in vivo conditions more closely than Luria broth (growth in human urine
      and under iron limitation and osmotic stress) were also used. Thirty-seven
      antigens to which a humoral response had been mounted, including 23 outer
      membrane proteins, were identified. These antigens are presumably expressed
      during urinary tract infection. Protein targets that are both actively required
      for virulence and antigenic may serve as protective antigens for vaccination;
      thus, five representative antigens were selected for use in virulence studies.
      Strains of P. mirabilis with mutations in three of the corresponding genes (the
      PMI0047 gene, rafY, and fadL) were not attenuated in the murine model of urinary
      tract infection. Putative iron acquisition proteins PMI0842 and PMI2596, however,
      both contribute to fitness in the urinary tract and thus emerge as vaccine
      candidates.

PMID- 18625735
TI  - Characterization of complement factor H binding to Yersinia enterocolitica
      serotype O:3.
AB  - A number of bacteria bind factor H (FH), the negative regulator of the
      alternative complement pathway, to avoid complement-mediated killing. Here we
      show that a gram-negative enteric pathogen, Yersinia enterocolitica serotype O:3,
      uses two virulence-related outer membrane (OM) proteins to bind FH. With Y.
      enterocolitica O:3 mutant strains displaying different combinations of surface
      factors relevant to complement resistance, we demonstrated that the major
      receptor for FH is the OM protein YadA. Another OM protein, Ail, also contributes
      to FH binding provided that it is not blocked by distal parts of the
      lipopolysaccharide (i.e., the O antigen and the outer core hexasaccharide).
      Importantly, we demonstrated that surface-bound FH was functional; both YadA- and
      Ail-bound FH displayed cofactor activity for factor I-mediated cleavage of C3b.
      With truncated recombinant FH constructs, we located the binding site of Ail
      specifically to short consensus repeats 6 and 7 of FH, while YadA showed a novel
      type of FH-binding pattern and appears to bind FH throughout the entire FH
      molecule. We thus conclude that Y. enterocolitica, via YadA and Ail, recruits
      functionally active FH to its surface. FH binding appears to be an important
      mechanism of the complement resistance of this pathogen.

PMID- 18625736
TI  - Descriptive science.

PMID- 18625737
TI  - In vivo demonstration and quantification of intracellular Bacillus anthracis in
      lung epithelial cells.
AB  - Inhalational anthrax is initiated by the entry of Bacillus anthracis spores into
      the lung. A critical early event in the establishment of an infection is the
      dissemination of spores from the lung. Using in vitro cell culture assays, we
      previously demonstrated that B. anthracis spores are capable of entering into
      epithelial cells of the lung and crossing a barrier of lung epithelial cells
      without apparent disruption of the barrier integrity, suggesting a novel portal
      for spores to disseminate from the lung. However, in vivo evidence for spore
      uptake by epithelial cells has been lacking. Here, using a mouse model, we
      present evidence that B. anthracis spores are taken up by lung epithelial cells
      in vivo soon after spores are delivered into the lung. Immunofluorescence
      staining of thin sections of lungs from spore-challenged BALB/c mice revealed
      that spores were associated with the epithelial surfaces in the airway and the
      alveoli at 2 and 4 h postinoculation. Confocal analysis further indicated that
      some of the associated spores were surrounded by F-actin, demonstrating
      intracellular localization. These observations were further confirmed and
      substantiated by a quantitative method that first isolated lung cells from spore
      challenged mice and then stained these cells with antibodies specific for
      epithelial cells and spores. The results showed that substantial amounts of
      spores were taken up by lung epithelial cells in vivo. These data, combined with
      those in our previous reports, provided powerful evidence that the lung epithelia
      were directly targeted by B. anthracis spores at early stages of infection.

PMID- 18625738
TI  - The absence of cutaneous lymph nodes results in a Th2 response and increased
      susceptibility to Leishmania major infection in mice.
AB  - Lymph nodes (LNs) are important sentinel organs where antigen-presenting cells
      interact with T cells to induce adaptive immune responses. In cutaneous infection
      of mice with Leishmania major, resistance depends on the induction of a T-helper
      cell-1 (Th1)-mediated cellular immune response in draining, peripheral LNs. We
      investigated whether draining, peripheral LNs are absolutely required for
      resistance against L. major infection. We investigated the course of experimental
      leishmaniasis in wild-type (wt) mice lacking peripheral LNs (pLNs), which we
      generated by in utero blockade of membrane-bound lymphotoxin, and in mice lacking
      pLNs or all LNs due to genetic deletion of lymphotoxin ligands or receptors. wt
      mice of the resistant C57BL/6 strain without local skin-draining LNs were still
      able to generate specific T-cell responses, but this yielded Th2 cells. This
      switch to a Th2 response resulted in severe systemic infection. We also confirmed
      these results with mice lacking pLNs due to genetic depletion of lymphotoxin
      beta. The complete absence of LNs due to a genetic depletion of the lymphotoxin
      beta receptor also resulted in a marked deterioration of disease and a Th2
      response. Thus, in the absence of pLNs, an L. major-specific Th2 response is
      induced in the remaining secondary lymphoid organs, such as the spleen and non
      skin-draining LNs. This indicates a critical requirement for pLNs to induce
      protective Th1 immunity and suggests that whether Th1 or Th2 priming to the same
      antigen occurs depends on the site of the primary antigen recognition.

PMID- 18625739
TI  - Immunological dominance of Trypanosoma cruzi tandem repeat proteins.
AB  - Proteins with tandem repeat (TR) domains have been found in various protozoan
      parasites, often acting as targets of B-cell responses. However, the extent of
      the repeats within Trypanosoma cruzi, the causative agent of Chagas' disease, has
      not been examined well. Here, we present a systematic survey of the TR genes
      found in T. cruzi, in comparison with other organisms. Although the
      characteristics of TR genes varied from organism to organism, the presence of
      genes having large TR domains was unique to the trypanosomatids examined,
      including T. cruzi. Sequence analyses of T. cruzi TR genes revealed their
      divergency; they do not share such characteristics as sequence similarity or
      biased cellular location predicted by the presence of a signal sequence or
      transmembrane domain(s). In contrast, T. cruzi TR proteins seemed to possess
      significant antigenicity. A number of previously characterized T. cruzi antigens
      were detected by this computational screening, and several of those antigens
      contained a large TR domain. Further analyses of the T. cruzi genome demonstrated
      that previously uncharacterized TR proteins in this organism may also be
      immunodominant. Taken together, T. cruzi is rich in large TR domain-containing
      proteins with immunological significance; it is worthwhile further analyzing such
      characteristics of TR proteins as the copy number and consensus sequence of the
      repeats to determine whether they might contribute to the biological variability
      of T. cruzi strains with regard to induced immunological responses, host
      susceptibility, disease outcomes, and pathogenicity.

PMID- 18625740
TI  - Inhibition of Salmonella enterica serovar typhimurium motility and entry into
      epithelial cells by a protective antilipopolysaccharide monoclonal immunoglobulin
      A antibody.
AB  - Secretory immunoglobulin A (SIgA) antibodies directed against the O antigen of
      lipopolysaccharide (LPS) are the primary determinants of mucosal immunity to gram
      negative enteric pathogens. However, the underlying mechanisms by which these
      antibodies interfere with bacterial colonization and invasion of intestinal
      epithelial cells are not well understood. In this study, we report that Sal4, a
      protective, anti-O5-specific monoclonal IgA, is a potent inhibitor of Salmonella
      enterica serovar Typhimurium flagellum-based motility. Using video light
      microscopy, we observed that Sal4 completely and virtually instantaneously
      "paralyzed" laboratory and clinical strains of serovar Typhimurium. Sal4-mediated
      motility arrest preceded and occurred independently of agglutination. Polyclonal
      anti-LPS IgG antibodies and F(ab)(2) fragments were as potent as was Sal4 at
      impeding bacterial motility, whereas monovalent Fab fragments were 5- to 10-fold
      less effective. To determine whether motility arrest can fully account for Sal4's
      protective capacity in vitro, we performed epithelial cell infection assays in
      which the requirement for flagellar motility in adherence and invasion was
      bypassed by centrifugation. Under these conditions, Sal4-treated serovar
      Typhimurium cells remained noninvasive, revealing that the monoclonal IgA, in
      addition to interfering with motility, has an effect on bacterial uptake into
      epithelial cells. Sal4 did not, however, inhibit bacterial uptake into mouse
      macrophages, indicating that the antibody interferes specifically with Salmonella
      pathogenicity island 1 (SPI-1)-dependent, but not SPI-1-independent, entry into
      host cells. These results reveal a previously unrecognized capacity of SIgA to
      "disarm" microbial pathogens on mucosal surfaces and prevent colonization and
      invasion of the intestinal epithelium.

PMID- 18625741
TI  - Characteristics of biofilm formation by Streptococcus mutans in the presence of
      saliva.
AB  - Interactions between salivary agglutinin and the adhesin P1 of Streptococcus
      mutans contribute to bacterial aggregation and mediate sucrose-independent
      adherence to tooth surfaces. We have examined biofilm formation by S. mutans
      UA159, and derivative strains carrying mutations affecting the localization or
      expression of P1, in the presence of fluid-phase or adsorbed saliva or salivary
      agglutinin preparations. Whole saliva- and salivary agglutinin-induced
      aggregation of S. mutans was adversely affected by the loss of P1 and sortase
      (SrtA) but not by the loss of trigger factor (RopA). Fluid-phase salivary
      agglutinin and, to a lesser extent, immobilized agglutinin inhibited biofilm
      development by S. mutans in the absence of sucrose, and whole saliva was more
      effective at decreasing biofilm formation than salivary agglutinin. Inhibition of
      biofilm development by salivary agglutinin was differently influenced by
      particular mutations, with the P1-deficient strain displaying a greater
      inhibition of biofilm development than the SrtA- or RopA-deficient strains. As
      expected, biofilm-forming capacities of all strains in the presence of salivary
      preparations were markedly enhanced in the presence of sucrose, although biofilm
      formation by the mutants was less efficient than that by the parental strain.
      Aeration strongly inhibited biofilm development, and the presence of salivary
      components did not restore biofilm formation in aerated conditions. The results
      disclose a potent ability of salivary constituents to moderate biofilm formation
      by S. mutans through P1-dependent and P1-independent pathways.

PMID- 18625742
TI  - The failure of immune response evasion by linear plasmid 28-1-deficient Borrelia
      burgdorferi is attributable to persistent expression of an outer surface protein.
AB  - Infectivity and persistence by Borrelia burgdorferi, the etiologic agent of Lyme
      disease, rely stringently on regulatory events. Among these is the downregulation
      of lipoprotein antigen expression, exemplified by outer surface protein C (OspC),
      at the advent of specific immunity in the mammalian host. B. burgdorferi
      spirochetes that lack the linear plasmid 28-1 (lp28-1) succumb to the host's
      immune response. We thus explored the notion that these two phenomena were
      related--that lp28-1(-) organisms fail to downregulate ospC and thus are cleared
      following the appearance of anti-OspC antibody in the murine host. The lp-28-1(-)
      isolate and a wild-type (wt) isolate bearing the complete set of plasmids were
      grown in dialysis membrane chambers that were implanted into rat peritoneal
      cavities. Analysis of mRNA and protein from these cultures showed that OspC
      expression levels by lp28-1(-) organisms are abnormally high in vivo. A time
      course analysis of ospC expression in tissues following infection indicates also
      that temporal diminution of the dominant antigen OspC is impaired in lp28-1(-)
      spirochetes. Finally, passive transfer of monoclonal OspC-specific antibody into
      SCID mice 8 days postinfection cleared lp28-1(-) spirochetes, yet the wt
      organisms persisted in a majority of animals. These findings indicate that
      incomplete repression of OspC by lp28-1(-) organisms renders them susceptible to
      immune-mediated clearance. The lp28-1 plasmid must harbor one or more genes
      involved in OspC downregulation.

PMID- 18625743
TI  - Complementation of a pathogenic IFNGR2 misfolding mutation with modifiers of N
      glycosylation.
AB  - Germline mutations may cause human disease by various mechanisms. Missense and
      other in-frame mutations may be deleterious because the mutant proteins are not
      correctly targeted, do not function correctly, or both. We studied a child with
      mycobacterial disease caused by homozygosity for a novel in-frame microinsertion
      in IFNGR2. In cells transfected with the mutant allele, most of the interferon
      gamma receptor 2 (IFN-gamma R2) protein was retained within the cell, and that
      expressed on the cell surface had an abnormally high molecular weight (MW). The
      misfolding mutation was not gain-of-glycosylation, as it created no new N
      glycosylation site. The mutant IFNGR2 allele was null, as the patient's cells did
      not respond to IFN-gamma. Based on the well-established relationship between
      protein N-glycosylation and protein quality control processes, we tested 29
      compounds affecting maturation by N-glycosylation in the secretory pathway.
      Remarkably, up to 13 of these compounds reduced the MW of surface-expressed
      mutant IFN-gamma R2 molecules and restored cellular responsiveness to IFN-gamma.
      Modifiers of N-glycosylation may therefore complement human cells carrying in
      frame and misfolding, but not necessarily gain-of-glycosylation, mutations in
      genes encoding proteins subject to trafficking via the secretory pathway. Some of
      these compounds are available for clinical use, paving the way for clinical
      trials of chemical complementation for various human genetic traits.

PMID- 18625744
TI  - Transvection mediated by the translocated cyclin D1 locus in mantle cell
      lymphoma.
AB  - In mantle cell lymphoma (MCL) and some cases of multiple myeloma (MM), cyclin D1
      expression is deregulated by chromosome translocations involving the
      immunoglobulin heavy chain (IgH) locus. To evaluate the mechanisms responsible,
      gene targeting was used to study long-distance gene regulation. Remarkably, these
      targeted cell lines lost the translocated chromosome (t(11;14)). In these MCL and
      MM cells, the nonrearranged cyclin D1 (CCND1) locus reverts from CpG
      hypomethylated to hypermethylated. Reintroduction of the translocated chromosome
      induced a loss of methylation at the unrearranged CCND1 locus, providing evidence
      of a transallelic regulatory effect. In these cell lines and primary MCL patient
      samples, the CCND1 loci are packaged in chromatin-containing CCCTC binding factor
      (CTCF) and nucleophosmin (NPM) at the nucleolus. We show that CTCF and NPM are
      bound at the IgH 3' regulatory elements only in the t(11;14) MCL cell lines.
      Furthermore, NPM short hairpin RNA produces a specific growth arrest in these
      cells. Our data demonstrate transvection in human cancer and suggest a functional
      role for CTCF and NPM.

PMID- 18625745
TI  - Avidity maturation of memory CD8 T cells is limited by self-antigen expression.
AB  - Immune tolerance to self-antigens is a complex process that utilizes multiple
      mechanisms working in concert to maintain homeostasis and prevent autoimmunity.
      We developed a system that revealed a population of self-specific CD8 T cells
      within the endogenous T cell repertoire. Immunization of ovalbumin (OVA)
      expressing transgenic mice with recombinant viruses expressing OVA-peptide
      variants induced self-reactive T cells in vivo that matured into memory T cells
      able to respond to secondary infection. However, whereas the avidity of memory
      cells in normal mice increased dramatically with repeated immunizations, avidity
      maturation was limited for self-specific CD8 T cells. Despite decreased avidity,
      such memory cells afforded protection against infection, but did not induce overt
      autoimmunity. Further, up-regulation of self-antigen expression in dendritic
      cells using an inducible system promoted programmed death-1 expression, but not
      clonal expansion of preexisting memory cells. Thus, the self-reactive T cell
      repertoire is controlled by overlapping mechanisms influenced by antigen dose.

PMID- 18625746
TI  - Discriminating gene expression profiles of memory B cell subpopulations.
AB  - Morphologically and functionally distinct subpopulations of human memory B
      (B(Mem)) cells are identifiable by either their expression of CD27 or Fc receptor
      like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong
      inhibitory potential. We have conducted comparative transcriptome and proteome
      analyses of FCRL4(+) and FCRL4(-) B(Mem) cells and found that these two subsets
      have very distinctive expression profiles for genes encoding transcription
      factors, cell-surface proteins, intracellular signaling molecules, and modifiers
      of the cell-cycle status. Among the differentially expressed transcription
      factors, runt-related transcription factor 1 (RUNX1) transcript levels were up
      regulated in FCRL4(-) cells, whereas RUNX2 transcripts were preferentially
      detected in FCRL4(+) cells. In vitro evidence for FCRL4 promoter responsiveness
      and in vivo promoter occupancy suggested that RUNX transcription factors are
      involved in the generation of these B(Mem) cell subpopulations. A distinctive
      signature profile was defined for the FCRL4(+) B(Mem) cells by their expression
      of CD11c, receptor activator for nuclear factor kappaB ligand, and FAS cell
      surface proteins, in combination with increased levels of SOX5, RUNX2, DLL1, and
      AICDA expression. We conclude that this recently identified subpopulation of
      B(Mem) cells, which normally resides in epithelial tissue-based niches, may serve
      a unique role in mucosal defense and, conversely, as a target for neoplastic
      transformation events.

PMID- 18625747
TI  - Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell
      compartment in HIV-infected viremic individuals.
AB  - Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody
      responses through mechanisms that remain poorly defined. A unique memory B cell
      subpopulation (CD20(hi)/CD27(lo)/CD21(lo)) in human tonsillar tissues was
      recently defined by the expression of the inhibitory receptor Fc-receptor-like-4
      (FCRL4). In this study, we describe a similar B cell subpopulation in the blood
      of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV
      viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched
      on B cells with a tissuelike memory phenotype (CD20(hi)/CD27(-)/CD21(lo)) when
      compared with B cells with a classical memory (CD27(+)) or naive (CD27(
      )/CD21(hi)) B cell phenotype. Tissuelike memory B cells expressed patterns of
      homing and inhibitory receptors similar to those described for antigen-specific T
      cell exhaustion. The tissuelike memory B cells proliferated poorly in response to
      B cell stimuli, which is consistent with high-level expression of multiple
      inhibitory receptors. Immunoglobulin diversities and replication histories were
      lower in tissuelike, compared with classical, memory B cells, which is consistent
      with premature exhaustion. Strikingly, HIV-specific responses were enriched in
      these exhausted tissuelike memory B cells, whereas total immunoglobulin and
      influenza-specific responses were enriched in classical memory B cells. These
      data suggest that HIV-associated premature exhaustion of B cells may contribute
      to poor antibody responses against HIV in infected individuals.

PMID- 18625748
TI  - A novel pathogenic pathway of immune activation detectable before clinical onset
      in Huntington's disease.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder
      characterized by both neurological and systemic abnormalities. We examined the
      peripheral immune system and found widespread evidence of innate immune
      activation detectable in plasma throughout the course of HD. Interleukin 6 levels
      were increased in HD gene carriers with a mean of 16 years before the predicted
      onset of clinical symptoms. To our knowledge, this is the earliest plasma
      abnormality identified in HD. Monocytes from HD subjects expressed mutant
      huntingtin and were pathologically hyperactive in response to stimulation,
      suggesting that the mutant protein triggers a cell-autonomous immune activation.
      A similar pattern was seen in macrophages and microglia from HD mouse models, and
      the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune
      activation, suggesting that immune dysfunction plays a role in brain pathology.
      Collectively, our data suggest parallel central nervous system and peripheral
      pathogenic pathways of immune activation in HD.

PMID- 18625750
TI  - Biomass fuels and respiratory diseases: a review of the evidence.
AB  - Globally, about 50% of all households and 90% of rural households use solid fuels
      (coal and biomass) as the main domestic source of energy, thus exposing
      approximately 50% of the world population-close to 3 billion people-to the
      harmful effects of these combustion products. There is strong evidence that acute
      respiratory infections in children and chronic obstructive pulmonary disease in
      women are associated with indoor biomass smoke. Lung cancer in women has been
      clearly associated with household coal use. Other conditions such as chronic
      obstructive pulmonary disease in men and tuberculosis could be also associated
      but evidence is scarce. According to estimates of the World Health Organization,
      more than 1.6 million deaths and over 38.5 million disability-adjusted life-years
      can be attributable to indoor smoke from solid fuels affecting mainly children
      and women. Interventions to suppress or reduce indoor exposure include behavior
      changes, improvements of household ventilation, improvements of stoves, and,
      outstandingly, transitions to better and cleaner fuels. These changes face
      personal and local beliefs and economic and sociocultural conditions. In
      addition, selection of fuels should consider cost, sustainability, and protection
      of the environment. Consequently, complex solutions need to be locally adapted,
      and involve the commitment and active participation of governments, scientific
      societies, nongovernmental organizations, and the general community.

PMID- 18625749
TI  - Immune-driven recombination and loss of control after HIV superinfection.
AB  - After acute HIV infection, CD8(+) T cells are able to control viral replication
      to a set point. This control is often lost after superinfection, although the
      mechanism behind this remains unclear. In this study, we illustrate in an HLA
      B27(+) subject that loss of viral control after HIV superinfection coincides with
      rapid recombination events within two narrow regions of Gag and Env. Screening
      for CD8(+) T cell responses revealed that each of these recombination sites
      (approximately 50 aa) encompassed distinct regions containing two immunodominant
      CD8 epitopes (B27-KK10 in Gag and Cw1-CL9 in Env). Viral escape and the
      subsequent development of variant-specific de novo CD8(+) T cell responses
      against both epitopes were illustrative of the significant immune selection
      pressures exerted by both responses. Comprehensive analysis of the kinetics of
      CD8 responses and viral evolution indicated that the recombination events quickly
      facilitated viral escape from both dominant WT- and variant-specific responses.
      These data suggest that the ability of a superinfecting strain of HIV to overcome
      preexisting immune control may be related to its ability to rapidly recombine in
      critical regions under immune selection pressure. These data also support a role
      for cellular immune pressures in driving the selection of new recombinant forms
      of HIV.

PMID- 18625751
TI  - An official ATS conference proceedings: advances in small-animal imaging
      application to lung pathophysiology.

PMID- 18625752
TI  - Patients with pulmonary arterial hypertension in clinical trials: who are they?
AB  - Results from clinical trials serve as the basis for approval of therapies by
      regulatory agencies as well as for treatment decisions by clinicians. But these
      findings are relevant only to patients who are similar to the ones enrolled into
      the trials. This is germane to clinical trials on pulmonary arterial hypertension
      (PAH) because the disease is uncommon but highly heterogeneous and results can
      easily be misapplied. The characteristics of patients entering the trials are
      largely determined by inclusion/exclusion criteria, with the result that most
      participants have idiopathic, connective tissue disease- and congenital heart
      disease-related PAH. Earlier trials enrolled patients mainly with New York Heart
      Association functional class III and IV disease and with severe pulmonary
      hemodynamic abnormalities. Because it has been the major outcome variable in most
      of the trials, eligibility is also dependent on six-minute-walk distance,
      ensuring that patients are moderately but not too severely functionally impaired,
      thereby maximizing the likelihood of detecting a favorable response to therapy.
      More recent trials have enrolled less ill patients, with more patients with New
      York Heart Association functional class II disease, less severe hemodynamic
      abnormalities, and more stability over time. This reflects, in part, ethical
      concerns about enrolling sicker patients into placebo-controlled trials. Trials
      have mainly enrolled white females in their 40s and 50s and have consistently
      excluded non-WHO group 1 forms of pulmonary hypertension. These characteristics
      must be carefully considered when applying the findings of pulmonary hypertension
      trials in clinical practice.

PMID- 18625753
TI  - Traditional and alternative designs for pulmonary arterial hypertension trials.
AB  - This article elaborates on the phases of drug development and trial design for
      pulmonary arterial hypertension, emphasizing the need for learning trials to
      assess efficacy signals before confirming trials. In this new era in pulmonary
      arterial hypertension, we need to reconsider innovative trial designs to maximize
      efficiency and pursue agents with the greatest potential for cure.

PMID- 18625754
TI  - Surrogate and combined end points in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is a rare and often devastating disease, although
      various effective therapies are now available. Clinical trials have used
      hemodynamic, cardiac imaging, laboratory, and exercise measurements as surrogate
      and intermediate end points in pulmonary arterial hypertension. Yet, based on the
      current literature, it is difficult to surmise which of these (if any) have been
      definitively validated. In addition, investigators have advocated the use of
      combined clinical end points in future clinical trials. The dependence of
      clinical trials and clinical management on such end points warrants a review of
      their use.

PMID- 18625755
TI  - Health-related quality of life and patient-reported outcomes in pulmonary
      arterial hypertension.
AB  - Advances in our understanding of the basic pathophysiology of pulmonary arterial
      hypertension (PAH) has led to an expanding number of therapeutic options. The
      ultimate goals of therapy are to lengthen survival while improving symptoms and
      quality of life. A wealth of research in other conditions has established health
      related quality of life (HRQoL) to be an important clinical endpoint. Until
      recently, however, little was known about HRQoL in PAH, and how best to measure
      it. Over the past few years, several studies have begun contributing to this
      growing area of research. Instruments used to assess HRQoL have varied between
      studies. The extent to which these instruments are valid in PAH depend on their
      specific measurement properties. In this article, we provide an overview of the
      different types of patient-reported outcomes (PROs) used in PAH, focusing in
      particular on the measurement of HRQoL. In the process, we review the current
      literature on HRQoL in PAH, summarize the available data from randomized
      controlled trials, and discuss the implications of these findings on future
      research. Despite significant progress, the study of HRQoL in PAH remains a
      nascent field relative to other conditions. As the use of PROs continues to
      increase, additional work will be needed to begin standardizing the reporting and
      interpretation of such outcomes in future clinical trials.

PMID- 18625756
TI  - The ethics of randomized clinical trials in pulmonary arterial hypertension.
AB  - Randomized clinical trials (RCTs) conducted during the past decade have shown
      that several therapies produce improvements in surrogate endpoints for patients
      with pulmonary arterial hypertension (PAH). Whether these therapies also
      influence clinical outcomes remains uncertain. These changes in the PAH landscape
      have raised several complex ethical issues regarding the conduct of RCTs in PAH,
      but to date, these issues have not been fully explored. In this article, we
      consider patients' potential motives for enrolling in PAH RCTs and identify those
      that are ethically acceptable. Second, we consider the efficiency of PAH RCTs-the
      ratio of the value of the information gained from RCTs to the risks and costs of
      obtaining it-and how this efficiency quotient contributes to a trial's ethics by
      enabling the fulfillment of patients' motives for participating. Third, we
      discuss the ethics of PAH RCTs using placebo control subjects versus those using
      active-treatment control subjects. Finally, we consider the ethical issues
      surrounding the roles of physician-investigators in PAH RCTs. We conclude with
      several recommendations, including (1) that investigators seek to ensure that
      patients enrolling in RCTs do so primarily to fulfill altruistic motives, (2)
      that research be conducted to determine the long-term risks associated with brief
      periods of withholding PAH therapies before further placebo-controlled trials
      without background therapies are conducted in PAH, and (3) that incentives for
      investigators to enroll more patients in PAH RCTs, such as enrollment-based
      authorship, be eliminated.

PMID- 18625758
TI  - Racial disparities in health care access and cardiovascular disease indicators in
      Black and White older adults in the Health ABC Study.
AB  - OBJECTIVE: Black adults consistently exhibit higher rates of and poorer health
      outcomes due to cardiovascular disease (CVD) than other racial groups,
      independent of differences in socioeconomic status (SES). Whether factors related
      to health care access can further explain racial disparities in CVD has not been
      thoroughly examined. METHOD: Using logistic regression, the authors examined
      racial and health care (i.e., health insurance and access to care) associations
      with CVD indicators (i.e., hypertension, low ankle-arm index, and left
      ventricular hypertrophy) in the Health, Aging, and Body Composition Study, a
      longitudinal study of well-functioning older adults. RESULTS: Older Black versus
      White adults had significantly worse health care. Overall, health care reduced
      the significant association between being Black and CVD only slightly, while race
      remained strongly associated with CVD after adjusting for demographics, SES, body
      mass index, and comorbidity. DISCUSSION: Research on health care quality may
      contribute to our understanding of these disparities.

PMID- 18625759
TI  - Assessing multiple medication use with probabilities of benefits and harms.
AB  - OBJECTIVE: A quantitative framework to assess harms and benefits of candidate
      medications in the context of drugs that a patient is already taking is proposed.
      METHOD: Probabilities of harms and benefits of a given medication are averaged to
      yield a utility value. The utility values of all medications under consideration
      are combined as a geometric mean to yield an overall measure of favorability. The
      grouping of medications yielding the highest favorability value is chosen.
      RESULTS: Five examples of choosing between widely used candidate medications
      demonstrate the feasibility of the proposed framework. DISCUSSION: The framework
      proposed provides a simple method for considering the trade-offs involved in
      prescribing multiple medications. It can be adapted to include additional
      parameters representing severity of condition, prioritization of outcomes,
      patient preferences, dosages, and medication interactions. Inconsistent reporting
      in the medical literature of data about benefits and harms of medications,
      dosages, and interactions constitutes its primary limitation.

PMID- 18625760
TI  - Determinants of self-rated health items with different points of reference:
      implications for health measurement of older adults.
AB  - OBJECTIVE: This study assessed whether three commonly used self-rated health
      (SRH) items (global, age-comparative, and self-comparative) are equivalent
      measures of health perception for older adults. METHOD: Regression analyses were
      used to simultaneously contrast the associations between physical, psychological,
      and social factors relating to health for three SRH items, in a large ( N =
      2,034) population-based sample of older adults (65 years and older) from the
      Australian Longitudinal Study of Aging. RESULTS: Health perceptions were more
      positive for the age-comparative SRH measure, compared to the pessimistic ratings
      of the self-comparative measure, particularly for the oldest-old adults.
      Different patterns of associations between the health factors and SRH measures
      were found. DISCUSSION: These results show the three SRH items are not equivalent
      measures of health and cannot be used interchangeably. The reference point of the
      SRH item has a considerable influence on health perceptions of older adults as it
      encapsulates unique health information.

PMID- 18625761
TI  - Content of advance directives for individuals with advanced dementia.
AB  - OBJECTIVE: To examine how people with end-stage dementia have conveyed their
      wishes for end-of-life care in advance directives. METHOD: The documents of 123
      residents of three Maryland nursing homes, all with end-stage dementia, were
      reviewed. RESULTS: More years of education and White race were significantly
      associated with having an advance directive. With the exceptions of comfort care
      and pain treatment, advance directives were used primarily to restrict, not
      request, many forms of care at the end of life. Decisions about care for end
      stage conditions such as Alzheimer's dementia are less often addressed in these
      documents than for terminal conditions and persistent vegetative state.
      DISCUSSION: For advance directives to better reflect a person's wishes,
      discussions with individuals and families about advance directives should include
      a range of care issues in the settings of terminal illness, persistent vegetative
      state or end-stage illness. These documents should be reviewed periodically to
      make certain that they convey accurately the person's treatment preferences.

PMID- 18625757
TI  - Stem cells and cell therapies in lung biology and lung diseases.

PMID- 18625763
TI  - Lack of a significant drug interaction between raltegravir and tenofovir.
AB  - Raltegravir is a novel human immunodeficiency virus type 1 (HIV-1) integrase
      inhibitor with potent in vitro activity (95% inhibitory concentration of 31 nM in
      50% human serum). This article reports the results of an open-label, sequential,
      three-period study of healthy subjects. Period 1 involved raltegravir at 400 mg
      twice daily for 4 days, period 2 involved tenofovir disoproxil fumarate (TDF) at
      300 mg once daily for 7 days, and period 3 involved raltegravir at 400 mg twice
      daily plus TDF at 300 mg once daily for 4 days. Pharmacokinetic profiles were
      also determined in HIV-1-infected patients dosed with raltegravir monotherapy
      versus raltegravir in combination with TDF and lamivudine. There was no
      clinically significant effect of TDF on raltegravir. The raltegravir area under
      the concentration time curve from 0 to 12 h (AUC(0-12)) and peak plasma drug
      concentration (C(max)) were modestly increased in healthy subjects (geometric
      mean ratios [GMRs], 1.49 and 1.64, respectively). There was no substantial effect
      of TDF on raltegravir concentration at 12 h postdose (C(12)) in healthy subjects
      (GMR [TDF plus raltegravir-raltegravir alone], 1.03; 90% confidence interval
      [CI], 0.73 to 1.45), while a modest increase (GMR, 1.42; 90% CI, 0.89 to 2.28)
      was seen in HIV-1-infected patients. Raltegravir had no substantial effect on
      tenofovir pharmacokinetics: C(24), AUC, and C(max) GMRs were 0.87, 0.90, and
      0.77, respectively. Coadministration of raltegravir and TDF does not change the
      pharmacokinetics of either drug to a clinically meaningful degree. Raltegravir
      and TDF may be coadministered without dose adjustments.

PMID- 18625762
TI  - Pharmacokinetics of high-dose lopinavir-ritonavir with and without saquinavir or
      nonnucleoside reverse transcriptase inhibitors in human immunodeficiency virus
      infected pediatric and adolescent patients previously treated with protease
      inhibitors.
AB  - Human immunodeficiency virus (HIV)-infected children and adolescents who are
      failing antiretrovirals may have a better virologic response when drug exposures
      are increased, using higher protease inhibitor doses or ritonavir boosting. We
      studied the pharmacokinetics and safety of high-dose lopinavir-ritonavir (LPV/r)
      in treatment-experienced patients, using an LPV/r dose of 400/100 mg/m(2) orally
      every 12 h (p.o. q12h) (without nonnucleoside reverse transcriptase inhibitor
      [NNRTI]), or 480/120 mg/m(2) p.o. q12h (with NNRTI). We calculated the LPV
      inhibitory quotient (IQ), and when the IQ was <15, saquinavir (SQV) 750 mg/m(2)
      p.o. q12h was added to the regimen. We studied 26 HIV-infected patients. The
      median age was 15 years (range, 7 to 17), with 11.5 prior antiretroviral
      medications, 197 CD4 cells/ml, viral load of 75,577 copies/ml, and a 133-fold
      change in LPV resistance. By treatment week 2, 14 patients had a viral-load
      decrease of >0.75 log(10), with a median maximal decrease in viral load of -1.57
      log(10) copies/ml at week 8. At week 2, 19 subjects showed a median LPV area
      under the concentration-time curve (AUC) of 157.2 (range, 62.8 to 305.5) microg x
      h/ml and median LPV trough concentration (C(trough)) of 10.8 (range, 4.1 to 25.3)
      microg/ml. In 16 subjects with SQV added, the SQV median AUC was 33.7 (range, 4.4
      to 76.5) microg x h/ml and the median SQV C(trough) was 2.1 (range, 0.2 to 4.1)
      microg/ml. At week 24, 18 of 26 (69%) subjects remained in the study. Between
      weeks 24 and 48, one subject withdrew for nonadherence and nine withdrew for
      persistently high virus load. In antiretroviral-experienced children and
      adolescents with HIV, high doses of LPV/r with or without SQV offer safe options
      for salvage therapy, but the modest virologic response and the challenge of
      adherence to a regimen with a high pill burden may limit the usefulness of this
      approach.

PMID- 18625764
TI  - Efficacy of quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives in experimental
      tuberculosis.
AB  - This study extends earlier reports regarding the in vitro efficacies of the 1,4
      di-N-oxide quinoxaline derivatives against Mycobacterium tuberculosis and has led
      to the discovery of a derivative with in vivo efficacy in the mouse model of
      tuberculosis. Quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives were tested in
      vitro against a broad panel of single-drug-resistant M. tuberculosis strains. The
      susceptibilities of these strains to some compounds were comparable to those of
      strain H(37)Rv, as indicated by the ratios of MICs for resistant and nonresistant
      strains, supporting the premise that 1,4-di-N-oxide quinoxaline derivatives have
      a novel mode of action unrelated to those of the currently used antitubercular
      drugs. Specific derivatives were further evaluated in a series of in vivo assays,
      including evaluations of the maximum tolerated doses, the levels of oral
      bioavailability, and the efficacies in a low-dose aerosol model of tuberculosis
      in mice. One compound, ethyl 7-chloro-3-methylquinoxaline-2-carboxylate 1,4
      dioxide, was found to be (i) active in reducing CFU counts in both the lungs and
      spleens of infected mice following oral administration, (ii) active against PA
      824-resistant Mycobacterium bovis, indicating that the pathway of
      bioreduction/activation is different from that of PA-824 (a bioreduced
      nitroimidazole that is in clinical trials), and (iii) very active against
      nonreplicating bacteria adapted to low-oxygen conditions. These data indicate
      that 1,4-di-N-oxide quinoxalines hold promise for the treatment of tuberculosis.

PMID- 18625765
TI  - Surveillance for neuraminidase inhibitor resistance among human influenza A and B
      viruses circulating worldwide from 2004 to 2008.
AB  - The surveillance of seasonal influenza virus susceptibility to neuraminidase (NA)
      inhibitors was conducted using an NA inhibition assay. The 50% inhibitory
      concentration values (IC(50)s) of 4,570 viruses collected globally from October
      2004 to March 2008 were determined. Based on mean IC(50)s, A(H3N2) viruses (0.44
      nM) were more sensitive to oseltamivir than A(H1N1) viruses (0.91 nM). The
      opposite trend was observed with zanamivir: 1.06 nM for A(H1N1) and 2.54 nM for
      A(H3N2). Influenza B viruses exhibited the least susceptibility to oseltamivir
      (3.42 nM) and to zanamivir (3.87 nM). To identify potentially resistant viruses
      (outliers), a threshold of a mean IC(50) value + 3 standard deviations was
      defined for type/subtype and drug. Sequence analysis of outliers was performed to
      identify NA changes that might be associated with reduced susceptibility.
      Molecular markers of oseltamivir resistance were found in six A(H1N1) viruses
      (H274Y) and one A(H3N2) virus (E119V) collected between 2004 and 2007. Some
      outliers contained previously reported mutations (e.g., I222T in the B viruses),
      while other mutations [e.g., R371K and H274Y in B viruses and H274N in A(H3N2)
      viruses) were novel. The R371K B virus outlier exhibited high levels of
      resistance to both inhibitors (>100 nM). A substantial variance at residue D151
      was observed among A(H3N2) zanamivir-resistant outliers. The clinical relevance
      of newly identified NA mutations is unknown. A rise in the incidence of
      oseltamivir resistance in A(H1N1) viruses carrying the H274Y mutation was
      detected in the United States and in other countries in the ongoing 2007 to 2008
      season. As of March 2008, the frequency of resistance among A(H1N1) viruses in
      the United States was 8.6% (50/579 isolates). The recent increase in oseltamivir
      resistance among A(H1N1) viruses isolated from untreated patients raises public
      health concerns and necessitates close monitoring of resistance to NA inhibitors.

PMID- 18625766
TI  - Comparative in vitro anti-hepatitis C virus activities of a selected series of
      polymerase, protease, and helicase inhibitors.
AB  - We report here a comparative study of the anti-hepatitis C virus (HCV) activities
      of selected (i) nucleoside polymerase, (ii) nonnucleoside polymerase, (iii)
      alpha,gamma-diketo acid polymerase, (iv) NS3 protease, and (v) helicase
      inhibitors, as well as (vi) cyclophilin binding molecules and (vii) alpha 2b
      interferon in four different HCV genotype 1b replicon systems.

PMID- 18625767
TI  - Heterocyclic compounds that inhibit Rev-RRE function and human immunodeficiency
      virus type 1 replication.
AB  - A cell-based screening assay was performed to identify compounds that inhibited
      the postintegration stage of the human immunodeficiency virus (HIV) life cycle.
      This assay utilized a cell line that contains the HIV gag and pol genes expressed
      in a Rev-dependent fashion. The cell line produces about 10 to 15 ng of p24 per
      milliliter of medium over a 24-h period in the form of viruslike particles. Any
      compound that inhibits a postintegration step in the HIV life cycle scores in
      this assay by decreasing particle production. Forty thousand compounds were
      screened, and 192 compounds were selected from the original screen because they
      showed more than 50% inhibition at a 10 muM concentration. The cumulative
      evidence presented in this study strongly suggests that 2 of the 192 compounds
      work as inhibitors of HIV Rev function. This was determined by a variety of cell
      based assays, although the compounds do not interfere with Rev-RRE (Rev response
      element) binding in vitro. Both compounds inhibit replication of the lab isolate
      NL4-3 as well as an HIV primary isolate from Brazil (93BR021) and thus are
      promising leads as therapeutic candidates that target HIV replication through
      inhibition of Rev function.

PMID- 18625768
TI  - In vivo pharmacodynamic target investigation for micafungin against Candida
      albicans and C. glabrata in a neutropenic murine candidiasis model.
AB  - Previous studies using in vivo candidiasis models have demonstrated that the
      concentration-associated pharmacodynamic indices, the maximum concentration of a
      drug in serum/MIC and 24-h area under the curve (AUC)/MIC, are associated with
      echinocandin treatment efficacy. The current investigations used a neutropenic
      murine model of disseminated Candida albicans and C. glabrata infection to
      identify the 24-h AUC/MIC index target associated with a stasis and killing
      endpoint for the echinocandin, micafungin. The kinetics after intraperitoneal
      micafungin dosing were determined in neutropenic infected mice. Peak levels and
      AUC values were linear over the 16-fold dose range studied. The serum drug
      elimination half-life ranged from 7.5 to 16 h. Treatment studies were conducted
      with 4 C. albicans and 10 C. glabrata isolates with micafungin MICs varying from
      0.008 to 0.25 microg/ml to determine whether similar 24-h AUC/MIC ratios were
      associated with efficacy. The free drug AUC/MICs associated with stasis and
      killing (1-log) endpoints were near 10 and 20, respectively. The micafungin
      exposures associated with efficacy were similar for the two Candida species.
      Furthermore, the free drug micafungin exposures required to produce stasis and
      killing endpoints were similar to those recently reported for another
      echinocandin, anidulafungin, against the identical Candida isolates in this
      model.

PMID- 18625769
TI  - In vitro profiling of ceftaroline against a collection of recent bacterial
      clinical isolates from across the United States.
AB  - This study evaluated the in vitro activity of ceftaroline, a novel cephalosporin
      with broad-spectrum activity against gram-negative and -positive pathogens,
      against 4,151 recent clinical isolates collected in the United States.
      Ceftaroline was very potent against bacteria found in community- and hospital
      acquired infections, including methicillin-resistant Staphylococcus aureus,
      multidrug-resistant Streptococcus pneumoniae, and common Enterobacteriaceae spp.

PMID- 18625770
TI  - Recombination and selection can remove blaTEM alleles from bacterial populations.
AB  - We passaged cells expressing TEM-1 and TEM-12 from a single plasmid through
      either ampicillin or ceftazidime. We found that the combined effects of
      recombination and selection removed the bla(TEM-1) allele from the bacterial
      population when it was passaged through ceftazidime or the bla(TEM-12) allele
      when cultures were passaged through ampicillin.

PMID- 18625771
TI  - Increasing trends in antimicrobial resistance among clinically important
      anaerobes and Bacteroides fragilis isolates causing nosocomial infections:
      emerging resistance to carbapenems.
AB  - This study reports data on the susceptibilities to five commonly used
      antianaerobic agents of five clinically frequently encountered anaerobes from
      2000 to 2007 and to Bacteroides fragilis isolates causing nosocomial infections
      from 1990 to 2006. There was a trend of decreasing susceptibilities of these
      anaerobes to ampicillin-sulbactam, cefmetazole, chloramphenicol, and clindamycin
      with time during the study period. The rates of susceptibility to clindamycin and
      cefmetazole for all clinical isolates of Bacteroides fragilis isolates were
      higher than those of isolates associated with nosocomial infections. The MICs of
      207 anaerobic blood isolates collected in 2006 to 14 antimicrobial agents were
      determined by the agar dilution method. The rates of nonsusceptibility to
      imipenem and meropenem were 7% and 12% for B. fragilis isolates (n = 60), 7% and
      3% for Bacteroides thetaiotamicron isolates (n = 30), 4% and 4% for Fusobacterium
      species (n = 27), 6% and 0% for Prevotella species (n = 16), 15% and 0% for
      Clostridium species (n = 28), and 0% and 0% for Peptostreptococcus species (n =
      32). The rates of susceptibility to moxifloxacin were 90% for B. fragilis
      isolates, 87% for B. thetaiotaomicron isolates, 81% for Fusobacterium species,
      75% for Prevotella species, 93% for Clostridium species, and 78% for
      Peptostreptococcus species. Thirty-six percent of Clostridium species and 12% of
      Peptostreptococcus species were not susceptible to metronidazole. Comparison of
      the data with the data from a previous survey from the same institute in 2002
      revealed higher rates of nonsusceptibility to carbapenems, especially for B.
      fragilis, Fusobacterium species, and Prevotella species isolates. The high rates
      of nonsusceptibility to commonly used antianaerobic agents mandate our attention,
      and periodic monitoring of the trend of the resistance is crucial.

PMID- 18625772
TI  - Genetic and structural insights into the dissemination potential of the extremely
      broad-spectrum class A beta-lactamase KPC-2 identified in an Escherichia coli
      strain and an Enterobacter cloacae strain isolated from the same patient in
      France.
AB  - Two clinical strains of Escherichia coli (2138) and Enterobacter cloacae (7506)
      isolated from the same patient in France and showing resistance to extended
      spectrum cephalosporins and low susceptibility to imipenem were investigated.
      Both strains harbored the plasmid-contained bla(TEM-1) and bla(KPC-2) genes.
      bla(KLUC-2), encoding a mutant of the chromosomal beta-lactamase of Kluyvera
      cryocrescens, was also identified at a plasmid location in E. cloacae 7506,
      suggesting the ISEcp1-assisted escape of bla(KLUC) from the chromosome.
      Determination of the KPC-2 structure at 1.6 A revealed that the binding site was
      occupied by the C-terminal (C-ter) residues coming from a symmetric KPC-2
      monomer, with the ultimate C-ter Glu interacting with Ser130, Lys234, Thr235, and
      Thr237 in the active site. This mode of binding can be paralleled to the
      inhibition of the TEM-1 beta-lactamase by the inhibitory protein BLIP.
      Determination of the 1.23-A structure of a KPC-2 mutant in which the five C-ter
      residues were deleted revealed that the catalytic site was filled by a citrate
      molecule. Structure analysis and docking simulations with cefotaxime and imipenem
      provided further insights into the molecular basis of the extremely broad
      spectrum of KPC-2, which behaves as a cefotaximase with significant activity
      against carbapenems. In particular, residues 104, 105, 132, and 167 draw a
      binding cavity capable of accommodating both the aminothiazole moiety of
      cefotaxime and the 6 alpha-hydroxyethyl group of imipenem, with the binding of
      the former drug being also favored by a significant degree of freedom at the
      level of the loop at positions 96 to 105 and by an enlargement of the binding
      site at the end of strand beta 3.

PMID- 18625773
TI  - Tipranavir-ritonavir genotypic resistance score in protease inhibitor-experienced
      patients.
AB  - To identify mutations associated with the virological response (VR) to a
      tipranavir-ritonavir (TPV/r)-based regimen, 143 patients previously treated with
      protease inhibitor (PI) were studied. VR was defined by a decrease of at least 1
      log(10) in, or undetectable, human immunodeficiency virus (HIV) RNA at month 3.
      The effect of each mutation in the protease, considering all variants at a
      residue as a single variable, on the VR to TPV/r was investigated. Mutations at
      six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E,
      Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was
      associated with a higher VR (F53L/W/Y). The genotypic score M36I/L/V-53L/W/Y +
      Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong
      association with VR. For the seven patients with a genotypic score of -1 (viruses
      with only mutation at codon 53), the percentage of responders was 100% and the
      percentages were 79%, 56%, 33%, 21%, and 0% for those with scores of 0, 1, 2, 3,
      and 4, respectively. The percentage of patients showing a response to TPV/r was
      lower for patients infected with non-clade B viruses (n = 16, all non-B subtypes
      considered together) than for those infected with clade B viruses (n = 127) (25%
      and 59%, respectively; P = 0.015). Most mutations associated with VR to TPV/r had
      not previously been associated with PI resistance. This is consistent with
      phenotypic analysis showing that TPV has a unique resistance profile. Mutations
      at five positions (35, 36, 61, 69, and 89) were observed significantly more
      frequently in patients infected with a non-B subtype than in those infected with
      the B subtype, probably explaining the lower VR observed in these patients.

PMID- 18625774
TI  - Immunomodulatory effects of voriconazole on monocytes challenged with Aspergillus
      fumigatus: differential role of Toll-like receptors.
AB  - Voriconazole (VRC) has activity against Aspergillus fumigatus, the most frequent
      cause of invasive aspergillosis in immunocompromised patients. The combination of
      VRC and A. fumigatus hyphae induced a more pronounced profile of expression of
      genes encoding inflammatory molecules in human monocytes than Aspergillus alone
      did. Herein, we provide further evidence of the potential mechanism underlying
      this immunomodulatory effect of VRC on human monocytes in response to A.
      fumigatus hyphae. A significant additive antifungal effect was shown when VRC was
      combined with monocytes against A. fumigatus hyphae. Both A. fumigatus hyphae and
      VRC induced pronounced profiles of mRNA and protein expression of Toll-like
      receptor 2 (TLR2) as well as tumor necrosis factor alpha (TNF-alpha) in THP-1
      monocytic cells compared to untreated cells. The VRC-induced increase was greater
      than that induced by hyphae. The combination of VRC and hyphae increased mRNA and
      protein expression of TLR2 and TNF-alpha to even higher levels than did either
      VRC or hyphae alone. In contrast, TLR4 expression, both at the mRNA and protein
      levels, was not increased by either VRC or hyphae or their combination. In
      addition, significantly more NF-kappaB was translocated to the nuclei of THP-1
      cells treated with VRC than untreated cells. While VRC induced more NF-kappaB
      than hyphae did, treatment with the combination of the two factors induced the
      greatest NF-kappaB expression. The pronounced profile of TLR2 signaling, TNF
      alpha expression, and NF-kappaB activation in the presence of VRC suggests an
      immunomodulatory effect leading to a more efficient response to A. fumigatus.

PMID- 18625775
TI  - Cell density and cell aging as factors modulating antifungal resistance of
      Candida albicans biofilms.
AB  - Biofilm formation is a major virulence attribute of Candida pathogenicity which
      contributes to higher antifungal resistance. We investigated the roles of cell
      density and cellular aging on the relative antifungal susceptibility of
      planktonic, biofilm, and biofilm-derived planktonic modes of Candida. A reference
      and a wild-type strain of Candida albicans were used to evaluate the MICs of
      caspofungin (CAS), amphotericin B (AMB), nystatin (NYT), ketoconazole (KTC), and
      flucytosine (5FC). Standard, NCCLS, and European Committee on Antibiotic
      Susceptibility Testing methods were used for planktonic MIC determination.
      Candida biofilms were then developed on polystyrene wells, and MICs were
      determined with a standard 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5
      [(phenylamino)carbonyl]-2H-tetrazolium hydroxide assay. Subsequently, antifungal
      susceptibility testing was performed for greater inoculum concentrations and 24-
      and 48-h-old cultures of planktonic Candida. Furthermore, Candida biofilm-derived
      planktonic cells (BDPC) were also subjected to antifungal susceptibility testing.
      The MICs for both C. albicans strains in the planktonic mode were low, although
      on increasing the inoculum concentration (up to 1 x 10(8) cells/ml), a variable
      MIC was noted. On the contrary, for Candida biofilms, the MICs of antifungals
      were 15- to >1,000-fold higher. Interestingly, the MICs for BDPC were lower and
      were similar to those for planktonic-mode cells, particularly those of CAS and
      AMB. Our data indicate that higher antifungal resistance of Candida biofilms is
      an intrinsic feature possibly related to the biofilm architecture rather than
      cellular density or cellular aging.

PMID- 18625776
TI  - Real-time PCR and statistical analyses of acrAB and ramA expression in clinical
      isolates of Klebsiella pneumoniae.
AB  - Clinical isolates of Klebsiella pneumoniae were tested for a correlation between
      tigecycline MIC and expression of ramA by using real-time PCR. At MICs of 4 and 8
      microg/ml, the expression of ramA was statistically significantly different from
      MICs of 2 microg/ml or less, supporting the tigecycline susceptibility breakpoint
      of <or=2 microg/ml for K. pneumoniae.

PMID- 18625777
TI  - In vitro and in vivo treatments of echinococcus protoscoleces and metacestodes
      with artemisinin and artemisinin derivatives.
AB  - In vitro treatment of Echinococcus multilocularis and Echinococcus granulosus
      larval stages with the antimalarials dihydroartemisinin and artesunate (10 to 40
      microM) exhibited promising results, while 6 weeks of in vivo treatment of mice
      infected with E. multilocularis metacestodes (200 mg/kg of body weight/day) had
      no effect. However, combination treatments of both drugs with albendazole led to
      a substantial but statistically not significant reduction in parasite weight
      compared to results with albendazole alone.

PMID- 18625778
TI  - Delay of active antimicrobial therapy and mortality among patients with
      bacteremia: impact of severe neutropenia.
AB  - Increasing bacterial antimicrobial resistance has prompted physicians to choose
      broad-spectrum antimicrobials in order to reduce the likelihood of inactive
      empirical therapy. However, for bacteremic patients already receiving supportive
      care, it is unclear whether delay of active antimicrobial therapy significantly
      impacts patient outcomes. We performed a retrospective cohort study of patients
      with monomicrobial bloodstream infections at a large urban hospital in the United
      States from 2001 to 2006. We assessed the impact of delay of active antimicrobial
      therapy on mortality by using multivariable logistic regression modeling with and
      without propensity score methodology. We evaluated 1,523 episodes of
      monomicrobial bacterial bloodstream infections at our institution. Nine hundred
      eighty-three bacteremic episodes (64.5%) were treated with an active
      antimicrobial agent within 24 h of the index blood culture; the remaining 540
      episodes (35.5%) were considered to have delay of active antimicrobial therapy.
      In adjusted analysis, among patients in the non-intensive-care-unit setting with
      an absolute neutrophil count (ANC) of <100 cells/microl, delay was associated
      with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI],
      2.84 to 114.5; P < 0.01); among intensive-care-unit patients with an ANC of <100
      cells/microl, the effect of delay on mortality was nearly significant (OR, 5.56;
      95% CI, 0.85 to 36.3; P = 0.07). However, for patients who were nonneutropenic
      (ANC, >500 cells/microl) or had ANCs of 100 to 500 cells/microl, delay was not
      associated with increased mortality. While the delay of active antimicrobial
      therapy was not significantly associated with higher mortality for most patients
      in this cohort, patients with severe neutropenia appeared to be vulnerable.

PMID- 18625779
TI  - In vitro and in vivo studies of the trypanocidal activity of a diarylthiophene
      diamidine against Trypanosoma cruzi.
AB  - Aromatic diamidines are DNA minor groove-binding ligands that display excellent
      antimicrobial activity against fungi, bacteria, and protozoa. Due to the
      currently unsatisfactory chemotherapy for Chagas' disease and in view of our
      previous reports regarding the effect of diamidines and analogues against both in
      vitro and in vivo Trypanosoma cruzi infection, this study evaluated the effects
      of a diarylthiophene diamidine (DB1362) against both amastigotes and bloodstream
      trypomastigotes of T. cruzi, the etiological agent of Chagas' disease. The data
      show the potent in vitro activity of DB1362 against both parasite forms that are
      relevant for mammalian infection at doses which do not exhibit cytotoxicity.
      Ultrastructural analysis and flow cytometry studies show striking alterations in
      the nuclei and mitochondria of the bloodstream parasites. In vivo studies were
      performed at two different drug concentrations (25 and 50 mg/kg/day) using a 2
      day or a 10-day regimen. The best results were obtained when acutely infected
      mice were treated with two doses at the lower concentration, resulting in 100%
      survival, compared to the infected and untreated mice. Although it did not
      display higher efficacy than benznidazole, DB1362 reduced both cardiac parasitism
      and inflammation, and in addition, it protected against the cardiac alterations
      (determined by measurements) common in T. cruzi infection. These results support
      further investigation of diamidines and related compounds as potential agents
      against Chagas' disease.

PMID- 18625780
TI  - Antimalarial activity of a new stilbene glycoside from Parthenocissus
      tricuspidata in mice.
AB  - A novel stilbene glycoside [piceid-(1-->6)-beta-d-glucopyranoside; PBG] from
      Parthenocissus tricuspidata was tested in vivo against Plasmodium berghei. PBG
      exhibited significant blood schizontocidal activity in a 4-day early infection, a
      repository evaluation, and an established infection, with a significant mean
      survival time comparable to that obtained with the standard drug, chloroquine (5
      mg x kg(-1) x day(-1)).

PMID- 18625781
TI  - Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone
      inhibitor of bacterial type II topoisomerases.
AB  - NXL101 is one of a new class of quinoline antibacterial DNA gyrase and
      topoisomerase IV inhibitors showing potent activity against gram-positive
      bacteria, including methicillin- and fluoroquinolone-resistant strains. NXL101
      inhibited topoisomerase IV more effectively than gyrase from Escherichia coli,
      whereas the converse is true of enzymes from Staphylococcus aureus. This apparent
      target preference is opposite to that which is associated with most
      fluoroquinolone antibiotics. In vitro isolation of S. aureus mutants resistant to
      NXL101 followed by cloning and sequencing of the genes encoding gyrase and
      topoisomerase IV led to the identification of several different point mutations
      within, or close to, the quinolone resistance-determining region (QRDR) of GyrA.
      However, the mutations were not those that are most frequently associated with
      decreased sensitivity to quinolones. A fluoroquinolone-resistant mutant variant
      of gyrase generated in vitro was highly resistant to inhibition by the
      fluoroquinolones ciprofloxacin and moxifloxacin but remained fully susceptible to
      inhibition by NXL101. Two mutant gyrases constructed in vitro, with mutations in
      gyrA engineered according to those most frequently found in S. aureus strains
      resistant to NXL101, were insensitive to inhibition by NXL101 and had a
      diminished sensitivity to ciprofloxacin and moxifloxacin. Certain combinations of
      mutations giving rise to NXL101 resistance and those giving rise to
      fluoroquinolone resistance may be mutually exclusive.

PMID- 18625783
TI  - Working memory deficits in children with specific learning disorders.
AB  - This article examines working memory functioning in children with specific
      developmental disorders of scholastic skills as defined by ICD-10. Ninety-seven
      second to fourth graders with a minimum IQ of 80 are compared using a 2 x 2
      factorial (dyscalculia vs. no dyscalculia; dyslexia vs. no dyslexia) design. An
      extensive test battery assesses the three subcomponents of working memory
      described by Baddeley (1986): phonological loop, visual-spatial sketchpad, and
      central executive. Children with dyscalculia show deficits in visual-spatial
      memory; children with dyslexia show deficits in phonological and central
      executive functioning. When controlling for the influence of the phonological
      loop on the performance of the central executive, however, the effect is no
      longer significant. Although children with both reading and arithmetic disorders
      are consistently outperformed by all other groups, there is no significant
      interaction between the factors dyscalculia and dyslexia.

PMID- 18625784
TI  - Social support moderates the relationship between gay community integration and
      sexual risk behavior among gay male couples.
AB  - Few studies of partnered gay men consider the social context within which sexual
      behaviors occur or investigate positive aspects of the social environment that
      may offset factors that are related to risky sexual behaviors. Fewer still
      include assessment of both individuals making up couples. Using an ecological
      framework and an actor-partner multilevel analysis approach, the authors
      investigate how three dimensions of gay community integration are related to
      individual sexual risk behavior among 108 individuals in 54 couples. They then
      investigate how general social support and partner-provided, HIV-specific social
      support moderate these relationships. An individual's gay community social
      engagement and general social support interact to predict sexual risk behavior,
      such that the apparent protective effect of social support is more pronounced
      among those with less social engagement. The association between partner-reported
      general social support and safer sexual behaviors is more pronounced among those
      whose partners disclose their gay identity to more people.

PMID- 18625785
TI  - Patients with heart failure who require an implantable defibrillator should have
      cardiac resynchronisation routinely.

PMID- 18625782
TI  - Development of oral reading fluency in children with speech or language
      impairments: a growth curve analysis.
AB  - This longitudinal study used piece-wise growth curve analyses to examine growth
      patterns in oral reading fluency for 1,991 students with speech impairments (SI)
      or language impairments (LI) from first through third grade. The main finding of
      this study was that a diagnosis of SI or LI can have a detrimental and persistent
      effect on early reading skills. Results indicated differences between subgroups
      in growth trajectories that were evident in first grade. A large proportion of
      students with SI or LI did not meet grade-level reading fluency benchmarks.
      Overall students with SI showed better performance than students with LI. Reading
      fluency performance was negatively related to the persistence of the SI or LI;
      the lowest performing students were those originally identified with SI or LI
      whose diagnosis changed to a learning disability. The results underscore the need
      to identify, monitor, and address reading fluency difficulties early among
      students with SI or LI.

PMID- 18625786
TI  - "Accordion effect" in reverse.

PMID- 18625787
TI  - Public-private partnerships in health: time for evidence-based policies.

PMID- 18625788
TI  - Cell therapy in acute myocardial infarction: measures of efficacy.

PMID- 18625789
TI  - Treating diastolic heart failure.

PMID- 18625790
TI  - Multislice CT: is it essential before atrial fibrillation ablation?

PMID- 18625791
TI  - Duchenne muscular dystrophy: how bad is the heart?

PMID- 18625792
TI  - Doin' the twist: new tools for an old concept of myocardial function.
AB  - It has been known for some time that the heart rotates during the cardiac cycle
      in concert with radial and longitudinal motion. With advances in imaging
      technology, it has been appreciated that the apex and base of the heart rotate in
      different directions, resulting in a twisting or torsional motion. A new
      echocardiographic technique, "speckle tracking imaging", permits accurate
      quantification of this motion. Torsion as well as the timing and magnitude of the
      rate of torsion (torsional velocity) may provide important new insights into
      cardiac physiology and disease.

PMID- 18625793
TI  - Paediatric heart care in India.
AB  - There have been few systematic efforts to define the burden of paediatric heart
      disease in India. Estimates based on published studies on congenital heart
      disease (CHD) at birth suggest a massive CHD burden. Absolute numbers of children
      with other heart diseases are also likely to be substantial. Given the enormity
      of the problem the number of paediatric heart programmes and specially trained
      paediatric cardiologists and paediatric cardiac surgeons are woefully inadequate.
      They are largely clustered in those parts of India that are experiencing
      improving economy and human development. For the average family the cost of care
      of a child with heart disease is prohibitive because care of children with heart
      disease often requires considerable human and material resources, together with
      sophisticated technology. While paediatric cardiology is only now being
      recognised in India as a major specialty, there is a need to intensify efforts to
      develop the specialty especially in those parts of India where there are very few
      centres. The present challenges are many and they include obtaining
      representative data on disease burden, establishing quality institutions with
      comprehensive paediatric cardiac programme training a cadre of professionals for
      paediatric heart care, developing cost-effective management strategies and
      improving awareness on diagnosis and management of paediatric heart diseases.

PMID- 18625794
TI  - Beyond dyssynchrony in cardiac resynchronisation therapy.
AB  - Cardiac resynchronisation therapy (CRT) in the form of biventricular pacing has
      emerged as a therapeutic option for patients with refractory heart failure.
      Patient selection and optimisation for CRT is based on the measurement of
      electromechanical ventricular dyssynchrony by electrocardiogram and
      echocardiographic techniques. The final common pathway for raising cardiac output
      on exertion is to minimise isovolumic time and maximise useful diastolic filling
      time, but correction of dyssynchrony alone may not lead to global improvement in
      about one-third of patients. Insights into pressure relations and abnormal
      timing, as well as clinical management, may hold the key to optimum outcome.

PMID- 18625795
TI  - Percutaneous closure of a large peri-prosthetic left ventricular pseudoaneurysm
      in a high-risk surgical candidate.

PMID- 18625796
TI  - Inverted left atrial appendage.

PMID- 18625797
TI  - Socioeconomic status and cardiovascular disease risk.

PMID- 18625798
TI  - Defining myocardial infarction: a work in progress: Ischaemic heart disease.

PMID- 18625799
TI  - Diagnosis and treatment of coronary artery disease in patients with chronic
      kidney disease: Ischaemic heart disease.

PMID- 18625800
TI  - Valvular and coronary heart disease in systemic inflammatory diseases: Systemic
      Disorders in heart disease.

PMID- 18625801
TI  - Human cutaneous microvascular ageing: potential insights into underlying
      physiological mechanisms of endothelial function and dysfunction.

PMID- 18625802
TI  - TRPA1: irritant detector of the airways.

PMID- 18625803
TI  - In the flicker of an eye.

PMID- 18625804
TI  - The contralateral knee joint in cruciate ligament deficiency.
AB  - BACKGROUND: Patients with unilateral ligament deficiency are believed to have
      altered kinematics of the contralateral knee, increasing the risk of
      contralateral joint injury. Therefore, the contralateral knees might not be a
      reliable normal kinematic control. PURPOSE: To compare the in vivo kinematics of
      the uninjured contralateral knees of patients with anterior or posterior cruciate
      ligament deficiency with knee kinematics of age-matched patients without joint
      injury. STUDY DESIGN: Controlled laboratory study. METHODS: Ten subjects with
      bilateral healthy knees, 10 patients with acute unilateral anterior cruciate
      ligament injury, and 10 with acute unilateral posterior cruciate ligament injury
      participated in this study. Kinematics were measured from 0 degrees to 90 degrees
      of flexion using imaging and 3-dimensional modeling. RESULTS: No significant
      differences were found across the groups in all rotations and translations during
      weightbearing flexion (P > .9). CONCLUSION: Patients with unilateral cruciate
      ligament deficiency did not alter kinematics of the contralateral uninjured knee
      during weightbearing flexion. In addition, these findings suggest that the
      included patients with anterior cruciate ligament or posterior cruciate ligament
      deficiency did not have preexisting abnormal kinematics of the knee. CLINICAL
      RELEVANCE: As the contralateral joint kinematics of the injured patients were not
      affected by the ipsilateral ligament injury in the short term, physicians and
      researchers might use the contralateral knee as a reliable normal kinematic
      control.

PMID- 18625805
TI  - The antianginal agent, ranolazine, reduces myocardial infarct size but does not
      alter anatomic no-reflow or regional myocardial blood flow in
      ischemia/reperfusion in the rabbit.
AB  - It has been suggested that ranolazine protects the ischemic/reperfused heart by
      reducing diastolic wall pressure during ischemia. However, there is limited
      information regarding the effect of ranolazine on the anatomic zone of no-flow in
      a model of acute myocardial occlusion/reperfusion. Before coronary artery
      occlusion (CAO), open-chest anesthetized rabbits were assigned to vehicle or
      ranolazine. Hearts received 60 minutes of CAO and 3 hours reperfusion. Ischemic
      risk zone was comparable in the 2 groups. Ranolazine significantly reduced
      infarct size. There was a non-significant trend for the no-reflow defect to be
      smaller in the ranolazine group. Regional myocardial blood flow was similar in
      both groups in the risk zone during ischemia and at 3 hours reperfusion. Heart
      rates were similar in both groups, whereas mean arterial pressure was reduced in
      the ranolazine group. While ranolazine was effective in reducing myocardial
      infarct size, the mechanism by which it did this was independent of improving
      perfusion during either ischemia or reperfusion, suggesting that ranolazine's
      effect of reducing infarct size involves alternative mechanisms.

PMID- 18625806
TI  - Talk of the town.

PMID- 18625808
TI  - Middle of the health care pack: Canada's performance in the 2007 Commonwealth
      Fund international survey.

PMID- 18625809
TI  - Ladies first: should boys be vaccinated against HPV?

PMID- 18625812
TI  - Rebuttal: should palliative care be a specialty?: no.

PMID- 18625813
TI  - Rebuttal: should palliative care be a specialty?: yes.

PMID- 18625816
TI  - Swallow your pride.

PMID- 18625817
TI  - Out of Africa.

PMID- 18625818
TI  - Screening change.

PMID- 18625819
TI  - Effects and treatment of inflammatory bowel disease during pregnancy.
AB  - QUESTION: I have several patients with inflammatory bowel disease (IBD) who are
      pregnant or planning pregnancies. What information can I give them regarding the
      possible effects of IBD on pregnancy and the medications used to treat IBD during
      pregnancy? ANSWER: Women with IBD appear to be at increased risk of giving birth
      prematurely, having low-birth-weight infants, and having cesarean sections.
      Neither 5-aminosalicylic acid nor sulfasalazine has been found to increase the
      rate of major malformations, fetal mortality, or morbidity. There is conflicting
      evidence regarding the use of corticosteroids and azathioprine and 6
      mercaptopurine. There are limited data on the use of infliximab during pregnancy,
      although no pattern of defects or complications has been reported to date.

PMID- 18625820
TI  - Dermacase. Keratoacanthoma.

PMID- 18625821
TI  - Medical palmistry: creating hyperlinked documents for the small screen.

PMID- 18625822
TI  - Recognition and treatment of serotonin syndrome.

PMID- 18625823
TI  - Update on pharmacologic and nonpharmacologic therapies for smoking cessation.
AB  - OBJECTIVE: To review the evidence on the efficacy and safety of pharmacologic and
      nonpharmacologic therapies for smoking cessation. QUALITY OF EVIDENCE: MEDLINE,
      EMBASE, and the Cochrane Database of Systematic Reviews were searched for
      randomized controlled trials, meta-analyses, and systematic reviews (level I
      evidence) pertinent to pharmacologic and nonpharmacologic smoking cessation
      therapies. MAIN MESSAGE: Pharmacologic smoking cessation aids are recommended for
      all smokers trying to quit, unless contraindicated. A new pharmacologic smoking
      cessation aid, varenicline, is now available in Canada. Level I evidence at 1
      year follow-up indicates that it is effective for smoking cessation. Adverse
      effects include nausea, insomnia, and abnormal dreaming. Nausea is mild or
      moderate and decreases over time. Varenicline is more effective than placebo or
      bupropion. Counseling also increases the likelihood of achieving cessation.
      CONCLUSION: Preliminary data indicate that varenicline is more effective than
      other available pharmacologic smoking cessation aids. Pharmacologic therapy
      should be combined with nonpharmacologic therapy.

PMID- 18625824
TI  - Healing the community to heal the individual: literature review of aboriginal
      community-based alcohol and substance abuse programs.
AB  - OBJECTIVE: To understand the development of culturally based and community-based
      alcohol and substance abuse treatment programs for aboriginal patients in an
      international context. SOURCES OF INFORMATION: MEDLINE, HealthSTAR, and PsycINFO
      databases and government documents were searched from 1975 to 2007. MeSH headings
      included the following: Indians, North American, Pacific ancestry group,
      aboriginal, substance-related disorders, alcoholism, addictive behaviour,
      community health service, and indigenous health. The search produced 150
      articles, 34 of which were relevant; most of the literature comprised opinion
      pieces and program descriptions (level III evidence). MAIN MESSAGE: Substance
      abuse in some aboriginal communities is a complex problem requiring culturally
      appropriate, multidimensional approaches. One promising perspective supports
      community-based programs or community mobile treatment. These programs ideally
      cover prevention, harm reduction, treatment, and aftercare. They often eliminate
      the need for people to leave their remote communities. They become focuses of
      community development, as the communities become the treatment facilities.
      Success requires solutions developed within communities, strong community
      interest and engagement, leadership, and sustainable funding. CONCLUSION:
      Community-based addictions programs are appropriate alternatives to treatment at
      distant residential addictions facilities. The key components of success appear
      to be strong leadership in this area; strong community-member engagement; funding
      for programming and organizing; and the ability to develop infrastructure for
      longterm program sustainability. Programs require increased documentation of
      their inroads in this developing field.

PMID- 18625825
TI  - Treating hand fractures: population-based study of acute health care use in
      British Columbia.
AB  - OBJECTIVE: To examine trends in use of acute health care services for hand
      fractures in a large diverse population across a range of medical settings.
      DESIGN: Retrospective review of data from the British Columbia Linked Health
      Dataset on patients who had been treated for hand fractures between May 1, 1996,
      and April 30, 2001. SETTING: British Columbia. PARTICIPANTS: A total of 72 481
      British Columbia residents identified from the British Columbia Linked Health
      Dataset as having received treatment for hand fractures. MAIN OUTCOME MEASURES:
      Initial treatment for fractures (who had provided treatment and where had the
      treatment taken place) and hospital use (type of hospital, physician responsible,
      wait time, length of stay,geographic variation). RESULTS: Almost all patients
      (97%) with hand fractures received initial treatment as outpatients. Just over
      half these patients (54%) received initial care in nonhospital settings, and more
      than two-thirds (70%) received initial care from primary care physicians. By far
      most patients (90%) were treated conservatively without surgical intervention.
      The few patients with more complicated hand fractures (10%) were most commonly
      treated in day surgery settings by specialist surgeons within 2 days of first
      presentation. Patients in the more rural, isolated,northern region of British
      Columbia had higher hospital admission rates (relative risk 2.1) for hand
      fractures than patients in other regions did. CONCLUSION: In contrast to other
      common fracture injuries that are routinely managed by specialist surgeons,most
      hand fractures in BC were managed initially as nonemergency medical problems by
      primary care physicians. Almost all patients were treated conservatively without
      surgical intervention. The few patients with more complicated hand fractures were
      referred to and treated quickly by specialist surgeons. Focused training and
      continuing education opportunities for primary care physicians on new approaches
      to management of acute hand fractures will ensure that patients with hand
      fractures in British Columbia and the whole of Canada continue to benefit from
      appropriate management by primary care physicians.

PMID- 18625826
TI  - Family physicians' perspectives on care of dementia patients and family
      caregivers.
AB  - OBJECTIVE: To identify factors that facilitate or impede family physicians in
      ambulatory care of patients with dementia and the family caregivers of such
      patients. DESIGN: Explanatory qualitative analyses of focus group discussions.
      SETTING: Large, medium, and small urban; suburban; and rural family practices
      from various regions of the province of Quebec. PARTICIPANTS: Twenty-five family
      doctors whose practices had at least 75% ambulatory patients; of these patients,
      an estimated minimum of 20% were 65 years old or older and at least 2% suffered
      from dementia. METHOD: Physicians were recruited by telephone to be paid
      participants in their regions in focus groups studying aspects of dementia care
      in ambulatory settings. Grounded theory and constant comparative methods were
      used to explore data from 3 French-speaking focus groups and 1 English-speaking
      focus group. MAIN FINDINGS: Physicians were 72% male, had a mean of 21.3 years in
      practice, and spent about 87% of their professional time in office practice. An
      estimated 38.7% of their patients were 65 years old or older, and 5.6% of these
      patients had Alzheimer disease or related dementias. Physicians were comfortable
      caring for these patients and their family caregivers but thought much of this
      care should come from support services offered elsewhere. Physicians admitted
      they had little knowledge of these services and had little interest in acquiring
      information about them. Government-run, community-based health and social service
      centres were the "black boxes" to which they referred patients and their
      caregivers for any form of help. Inconsistencies in the services offered by these
      centres were noted. CONCLUSION; While family doctors are seeking a more seamless
      form of interdisciplinary dementia care, a large amount of that care comes from
      support services about which physicians are not well informed and are not
      interested in learning.

PMID- 18625827
TI  - Rural intentions: factors affecting the career choices of family medicine
      graduates.
AB  - OBJECTIVE: To investigate the reasons for family medicine graduates' career
      choices. DESIGN: Qualitative study using focus groups and one-on-one interviews.
      SETTING: University of Calgary in Alberta. PARTICIPANTS: Seventeen male and
      female second-year family medicine residents, representing a range of ages and
      areas of origin, enrolled in the 2004 urban and rural south streams of the family
      medicine residency program at the University of Calgary. METHOD: During the final
      month of training, 2 focus groups were conducted to determine graduating
      students' career choices and the reasons for them. After focus-group data were
      analyzed, a questionnaire was constructed and subsequently administered to
      participants during face-to-face or telephone interviews. MAIN FINDINGS: Most
      residents initially planned to do urban locums in order to gain experience. In
      the long term, they planned to open practices in urban areas for lifestyle and
      family reasons. Many residents from the rural stream had no long-term plans to
      establish rural practices. Most residents said they felt prepared for practice,
      but many indicated that an optional third year of paid training, with an emphasis
      on emergency medicine, obstetrics, and pediatrics, would be desirable. Reasons
      cited for not practising in rural areas were related to workload, lifestyle
      issues, family obligations, and perceived lack of medical support in the
      community. Only 4 female graduates and 1 male graduate intended to practise
      obstetrics. The main reason residents gave for this was inadequate training in
      obstetrics during residency. Finances were cited as a secondary reason for many
      choices, and might in fact be more important than at first apparent. CONCLUSION:
      Despite its intention to recruit family medicine graduates to rural areas and to
      obstetrics, the University of Calgary residency training program was not
      successful in recruiting physicians to these areas. The program likely needs to
      re-examine the effectiveness of current approaches. If other programs are having
      similar difficulties recruiting graduates to obstetrics and rural practice,
      perhaps changes in policies should be considered.

PMID- 18625828
TI  - Bisphosphonate-associated osteonecrosis of the jaw.

PMID- 18625829
TI  - Punch biopsy: minor surgery video series.

PMID- 18625830
TI  - Environmental scans: how useful are they for primary care research?

PMID- 18625832
TI  - Lillooet, 2 km: reflections of a rural GP surgeon.

PMID- 18625833
TI  - Community of care.

PMID- 18625834
TI  - Out of bounds.

PMID- 18625838
TI  - Amy Kiger: Abuzz on cell biology. Interview by Caitlin Sedwick.

PMID- 18625839
TI  - Playing both sides: nucleophosmin between tumor suppression and oncogenesis.
AB  - Nucleophosmin (NPM) is frequently mutated in acute myeloid leukemias and is
      thought to act as both a proto-oncogene and a tumor suppressor. Although genetic
      and molecular evidence has shed light on the mechanisms of NPM-mediated tumor
      suppression, the potential role of NPM mutants as oncogenes remains ill defined.
      Now, new data provide a straightforward mechanism for this latter function, as
      NPM is shown to regulate the stability and the function of MYC. Remarkably, the
      same leitmotif of "placing a critical cell regulator in the wrong place at the
      wrong time" appears to underscore all the cancer-promoting activities of mutated
      NPM.

PMID- 18625840
TI  - Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7
      gamma.
AB  - Mutations leading to aberrant cytoplasmic localization of nucleophosmin (NPM) are
      the most frequent genetic alteration in acute myelogenous leukemia (AML). NPM
      binds the Arf tumor suppressor and protects it from degradation. The AML
      associated NPM mutant (NPMmut) also binds p19Arf but is unable to protect it from
      degradation, which suggests that inactivation of p19Arf contributes to
      leukemogenesis in AMLs. We report here that NPM regulates turnover of the c-Myc
      oncoprotein by acting on the F-box protein Fbw7gamma, a component of the E3
      ligase complex involved in the ubiquitination and proteasome degradation of c
      Myc. NPM was required for nucleolar localization and stabilization of Fbw7gamma.
      As a consequence, c-Myc was stabilized in cells lacking NPM. Expression of NPMmut
      also led to c-Myc stabilization because of its ability to interact with Fbw7gamma
      and delocalize it to the cytoplasm, where it is degraded. Because Fbw7 induces
      degradation of other growth-promoting proteins, the NPM-Fbw7 interaction emerges
      as a central tumor suppressor mechanism in human cancer.

PMID- 18625841
TI  - Mars promotes dTACC dephosphorylation on mitotic spindles to ensure spindle
      stability.
AB  - Microtubule-associated proteins (MAPs) ensure the fidelity of chromosome
      segregation by controlling microtubule (MT) dynamics and mitotic spindle
      stability. However, many aspects of MAP function and regulation are poorly
      understood in a developmental context. We show that mars, which encodes a
      Drosophila melanogaster member of the hepatoma up-regulated protein family of
      MAPs, is essential for MT stabilization during early embryogenesis. As well as
      associating with spindle MTs in vivo, Mars binds directly to protein phosphatase
      1 (PP1) and coimmunoprecipitates from embryo extracts with minispindles and
      Drosophila transforming acidic coiled-coil (dTACC), two MAPs that function as
      spindle assembly factors. Disruption of binding to PP1 or loss of mars function
      results in elevated levels of phosphorylated dTACC on spindles. A
      nonphosphorylatable form of dTACC is capable of rescuing the lethality of mars
      mutants. We propose that Mars mediates spatially controlled dephosphorylation of
      dTACC, which is critical for spindle stabilization.

PMID- 18625842
TI  - Structure of the actin-depolymerizing factor homology domain in complex with
      actin.
AB  - Actin dynamics provide the driving force for many cellular processes including
      motility and endocytosis. Among the central cytoskeletal regulators are actin
      depolymerizing factor (ADF)/cofilin, which depolymerizes actin filaments, and
      twinfilin, which sequesters actin monomers and caps filament barbed ends. Both
      interact with actin through an ADF homology (ADF-H) domain, which is also found
      in several other actin-binding proteins. However, in the absence of an atomic
      structure for the ADF-H domain in complex with actin, the mechanism by which
      these proteins interact with actin has remained unknown. Here, we present the
      crystal structure of twinfilin's C-terminal ADF-H domain in complex with an actin
      monomer. This domain binds between actin subdomains 1 and 3 through an interface
      that is conserved among ADF-H domain proteins. Based on this structure, we
      suggest a mechanism by which ADF/cofilin and twinfilin inhibit nucleotide
      exchange of actin monomers and present a model for how ADF/cofilin induces
      filament depolymerization by weakening intrafilament interactions.

PMID- 18625843
TI  - Primary microRNA transcript retention at sites of transcription leads to enhanced
      microRNA production.
AB  - MicroRNAs (miRNAs) are noncoding RNAs with important roles in regulating gene
      expression. In studying the earliest nuclear steps of miRNA biogenesis, we
      observe that primary miRNA (pri-miRNA) transcripts retained at transcription
      sites due to the deletion of 3'-end processing signals are converted more
      efficiently into precursor miRNAs (pre-miRNAs) than pri-miRNAs that are cleaved,
      polyadenylated, and released. Flanking exons, which also increase retention at
      transcription sites, likewise contribute to increased levels of intronic pri
      miRNAs. Consistently, efficiently processed endogenous pri-miRNAs are enriched in
      chromatin-associated nuclear fractions. In contrast, pri-miRNAs that accumulate
      to high nuclear levels after cleavage and polyadenylation because of the presence
      of a viral RNA element (the ENE of the Kaposi's sarcoma-associated herpes virus
      polyadenylated nuclear RNA) are not efficiently processed to precursor or mature
      miRNAs. Exogenous pri-miRNAs unexpectedly localize to nuclear foci containing
      splicing factor SC35; yet these foci are unlikely to represent sites of miRNA
      transcription or processing. Together, our results suggest that pri-miRNA
      processing is enhanced by coupling to transcription.

PMID- 18625844
TI  - Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian
      cells.
AB  - Deadenylation is the major step triggering mammalian mRNA decay. One consequence
      of deadenylation is the formation of nontranslatable messenger RNA (mRNA) protein
      complexes (messenger ribonucleoproteins [mRNPs]). Nontranslatable mRNPs may
      accumulate in P-bodies, which contain factors involved in translation repression,
      decapping, and 5'-to-3' degradation. We demonstrate that deadenylation is
      required for mammalian P-body formation and mRNA decay. We identify Pan2, Pan3,
      and Caf1 deadenylases as new P-body components and show that Pan3 helps recruit
      Pan2, Ccr4, and Caf1 to P-bodies. Pan3 knockdown causes a reduction of P-bodies
      and has differential effects on mRNA decay. Knocking down Caf1 or overexpressing
      a Caf1 catalytically inactive mutant impairs deadenylation and mRNA decay. P
      bodies are not detected when deadenylation is blocked and are restored when the
      blockage is released. When deadenylation is impaired, P-body formation is not
      restorable, even when mRNAs exit the translating pool. These results support a
      dynamic interplay among deadenylation, mRNP remodeling, and P-body formation in
      selective decay of mammalian mRNA.

PMID- 18625845
TI  - Cytopathicity of Chlamydia is largely reproduced by expression of a single
      chlamydial protease.
AB  - Chlamydiae replicate in a vacuole within epithelial cells and commonly induce
      cell damage and a deleterious inflammatory response of unknown molecular
      pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates
      from the vacuole to the cytosol, where it cleaves several cellular proteins. CPAF
      is synthesized as an inactive precursor that is processed and activated during
      infection. Here, we show that CPAF can be activated in uninfected cells by
      experimentally induced oligomerization, reminiscent of the activation mode of
      initiator caspases. CPAF activity induces proteolysis of cellular substrates
      including two novel targets, cyclin B1 and PARP, and indirectly results in the
      processing of pro-apoptotic BH3-only proteins. CPAF activation induces striking
      morphological changes in the cell and, later, cell death. Biochemical and
      ultrastructural analysis of the cell death pathway identify the mechanism of cell
      death as nonapoptotic. Active CPAF in uninfected human cells thus mimics many
      features of chlamydial infection, implicating CPAF as a major factor of
      chlamydial pathogenicity, Chlamydia-associated cell damage, and inflammation.

PMID- 18625846
TI  - Quantitative analysis of autophagy-related protein stoichiometry by fluorescence
      microscopy.
AB  - In yeast, approximately 31 autophagy-related (Atg) proteins have been identified.
      Most of them reside at the phagophore assembly site (PAS), although the function
      of the PAS mostly remains unclear. One reason for the latter is the lack of
      stoichiometric information regarding the Atg proteins at this site. We report the
      application of fluorescence microscopy to study the amount of Atg proteins at the
      PAS. We find that an increase in the amount of Atg11 at the PAS enhances the
      recruitment of Atg8 and Atg9 to this site and facilitates the formation of more
      cytoplasm-to-vacuole targeting vesicles. In response to autophagy induction, the
      amount of most Atg proteins remains unchanged at the PAS, whereas we see an
      enhanced recruitment of Atg8 and 9 at this site. During autophagy, the amount of
      Atg8 at the PAS showed a periodic change, indicating the formation of
      autophagosomes. Application of this method and further analysis will provide more
      insight into the functions of Atg proteins.

PMID- 18625848
TI  - Lectin microarrays identify cell-specific and functionally significant cell
      surface glycan markers.
AB  - Glycosylation is among the most complex posttranslational modifications with an
      extremely high level of diversity that has made it refractory to high-throughput
      analyses. Despite its resistance to high-throughput techniques, glycosylation is
      important in many critical cellular processes that necessitate a productive
      approach to their analysis. To facilitate studies in glycosylation, we developed
      a high-throughput lectin microarray for defining mammalian cell surface glycan
      signatures. Using the lectin microarray we established a binary analysis of cell
      binding and hierarchical organization of 24 mammalian cell lines. The array was
      also used to document changes in cell surface glycosylation during cell
      development and differentiation of primary murine immune system cells. To
      establish the biological and clinical importance of glycan signatures, the lectin
      microarray was applied in two systems. First, we analyzed the cell surface glycan
      signatures and were able to predict mannose-dependent tropism using a model
      pathogen. Second, we used the glycan signatures to identify novel lectin
      biomarkers for cancer stem-like cells in a murine model. Thus, lectin microarrays
      are an effective tool for analyzing diverse cell processes including cell
      development and differentiation, cell-cell communication, pathogen-host
      recognition, and cell surface biomarker identification.

PMID- 18625847
TI  - BRCA1 and Tip60 determine the cellular response to ultraviolet irradiation
      through distinct pathways.
AB  - The histone acetyltransferase Tip60 regulates the apoptotic response to
      ultraviolet (UV) irradiation. A previously suggested mechanism for this
      regulation consists of the ability of Tip60 to coactivate transcription by the
      tumor suppressor p53. In this study, we show that Tip60 is required for the early
      DNA damage response (DDR) to UV, including the phosphorylation of histone 2AX, c
      Jun N-terminal kinases (JNKs), and ataxia telangiectasia-related substrates. In
      contrast, p53 was not required for UV-induced DDR. Rather, p53 accumulation by
      either knockdown of Mdm2 or addition of an Mdm2 inhibitor, Nutlin-3, before
      irradiation strongly attenuated the UV-induced DDR and increased cell survival.
      This protective effect of preaccumulated p53 was mediated, at least in part, by
      the increased expression of CDKN1A/p21, subsequent down-regulation of BRCA1, and
      impaired JNK activation accompanied by decreased association of replication
      protein A with chromatin. We conclude that Tip60 enables UV-induced DDR signaling
      even in the absence of p53, whereas preaccumulated p53 suppresses UV-induced DDR
      by reducing the levels of BRCA1.

PMID- 18625849
TI  - Voltage clamp fluorimetry reveals a novel outer pore instability in a mammalian
      voltage-gated potassium channel.
AB  - Voltage-gated potassium (Kv) channel gating involves complex structural
      rearrangements that regulate the ability of channels to conduct K(+) ions.
      Fluorescence-based approaches provide a powerful technique to directly report
      structural dynamics underlying these gating processes in Shaker Kv channels.
      Here, we apply voltage clamp fluorimetry, for the first time, to study voltage
      sensor motions in mammalian Kv1.5 channels. Despite the homology between Kv1.5
      and the Shaker channel, attaching TMRM or PyMPO fluorescent probes to substituted
      cysteine residues in the S3-S4 linker of Kv1.5 (M394C-V401C) revealed unique and
      unusual fluorescence signals. Whereas the fluorescence during voltage sensor
      movement in Shaker channels was monoexponential and occurred with a similar time
      course to ionic current activation, the fluorescence report of Kv1.5 voltage
      sensor motions was transient with a prominent rapidly dequenching component that,
      with TMRM at A397C (equivalent to Shaker A359C), represented 36 +/- 3% of the
      total signal and occurred with a tau of 3.4 +/- 0.6 ms at +60 mV (n = 4). Using a
      number of approaches, including 4-AP drug block and the ILT triple mutation,
      which dissociate channel opening from voltage sensor movement, we demonstrate
      that the unique dequenching component of fluorescence is associated with channel
      opening. By regulating the outer pore structure using raised (99 mM) external
      K(+) to stabilize the conducting configuration of the selectivity filter, or the
      mutations W472F (equivalent to Shaker W434F) and H463G to stabilize the
      nonconducting (P-type inactivated) configuration of the selectivity filter, we
      show that the dequenching of fluorescence reflects rapid structural events at the
      selectivity filter gate rather than the intracellular pore gate.

PMID- 18625850
TI  - Linking exponential components to kinetic states in Markov models for single
      channel gating.
AB  - Discrete state Markov models have proven useful for describing the gating of
      single ion channels. Such models predict that the dwell-time distributions of
      open and closed interval durations are described by mixtures of exponential
      components, with the number of exponential components equal to the number of
      states in the kinetic gating mechanism. Although the exponential components are
      readily calculated (Colquhoun and Hawkes, 1982, Phil. Trans. R. Soc. Lond. B.
      300:1-59), there is little practical understanding of the relationship between
      components and states, as every rate constant in the gating mechanism contributes
      to each exponential component. We now resolve this problem for simple models. As
      a tutorial we first illustrate how the dwell-time distribution of all closed
      intervals arises from the sum of constituent distributions, each arising from a
      specific gating sequence. The contribution of constituent distributions to the
      exponential components is then determined, giving the relationship between
      components and states. Finally, the relationship between components and states is
      quantified by defining and calculating the linkage of components to states. The
      relationship between components and states is found to be both intuitive and
      paradoxical, depending on the ratios of the state lifetimes. Nevertheless, both
      the intuitive and paradoxical observations can be described within a consistent
      framework. The approach used here allows the exponential components to be
      interpreted in terms of underlying states for all possible values of the rate
      constants, something not previously possible.

PMID- 18625851
TI  - Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and
      enhanced cell death.
AB  - Duchenne muscular dystrophy (DMD) is a hereditary degenerative disease manifested
      by the absence of dystrophin, a structural, cytoskeletal protein, leading to
      muscle degeneration and early death through respiratory and cardiac muscle
      failure. Whereas the rise of cytosolic Ca(2+) concentrations in muscles of mdx
      mouse, an animal model of DMD, has been extensively documented, little is known
      about the mechanisms causing alterations in Na(+) concentrations. Here we show
      that the skeletal muscle isoform of the voltage-gated sodium channel, Na(v)1.4,
      which represents over 90% of voltage-gated sodium channels in muscle, plays an
      important role in development of abnormally high Na(+) concentrations found in
      muscle from mdx mice. The absence of dystrophin modifies the expression level and
      gating properties of Na(v)1.4, leading to an increased Na(+) concentration under
      the sarcolemma. Moreover, the distribution of Na(v)1.4 is altered in mdx muscle
      while maintaining the colocalization with one of the dystrophin-associated
      proteins, syntrophin alpha-1, thus suggesting that syntrophin is an important
      linker between dystrophin and Na(v)1.4. Additionally, we show that these
      modifications of Na(v)1.4 gating properties and increased Na(+) concentrations
      are strongly correlated with increased cell death in mdx fibers and that both
      cell death and Na(+) overload can be reversed by 3 nM tetrodotoxin, a specific
      Na(v)1.4 blocker.

PMID- 18625853
TI  - Abeta predictor of Alzheimer disease symptoms.

PMID- 18625852
TI  - Anticoagulation after cardioembolic stroke: to bridge or not to bridge?
AB  - BACKGROUND: Most patients with cardioembolic stroke require long-term
      anticoagulation. Still, uncertainty exists regarding the best mode of starting
      long-term anticoagulation. Design, Setting, and Patients We conducted a
      retrospective review of all patients with cardioembolic stroke admitted to our
      center from April 1, 2004, to June 30, 2006, and not treated with tissue
      plasminogen activator. Patients were grouped by treatment: no treatment, aspirin
      only, aspirin followed by warfarin sodium, intravenous heparin sodium in the
      acute phase followed by warfarin (heparin bridging), and full-dose enoxaparin
      sodium combined with warfarin (enoxaparin bridging). Outcome measures and adverse
      events were collected prospectively. Laboratory values were captured from the
      records. MAIN OUTCOME MEASURES: Symptomatic hemorrhagic transformation, stroke
      progression, and discharge modified Rankin Scale score. RESULTS: Two hundred four
      patients were analyzed. Recurrent stroke occurred in 2 patients (1%). Progressive
      stroke was the most frequent serious adverse event, seen in 11 patients (5%).
      Hemorrhagic transformation occurred in a bimodal distribution-an early benign
      hemorrhagic transformation and a late symptomatic hemorrhagic transformation. All
      of the symptomatic hemorrhagic transformation cases were in the enoxaparin
      bridging group (10%) (P = .003). Systemic bleeding occurred in 2 patients (1%)
      and was associated with heparin bridging (P = .04). CONCLUSIONS: Anticoagulation
      of patients with cardioembolic stroke can be safely started with warfarin shortly
      after stroke. Heparin bridging and enoxaparin bridging increase the risk for
      serious bleeding.

PMID- 18625854
TI  - Molecular predictors in glioblastoma: toward personalized therapy.
AB  - Recent therapeutic advances have improved standard treatment for patients with
      newly diagnosed glioblastoma. Unfortunately, even with these improvements, only a
      fraction of patients derive significant benefit and experience prolonged
      survival. These findings are consistent with long-standing clinical and recent
      molecular evidence that subtypes of glioblastoma exist with differing survival
      rates and response to treatment. However, patients with newly diagnosed
      glioblastoma are currently treated in a uniform fashion, without regard for
      potential underlying differences in molecular alterations or prognosis. In this
      review, we will discuss recent progress toward the identification of robust and
      clinically relevant molecular subgroups of glioblastoma and initial steps in
      using this information to individualize therapy and overcome treatment
      resistance.

PMID- 18625855
TI  - Rural-urban differences in acute stroke management practices: a modifiable
      disparity.
AB  - Acute stroke management practices in rural areas of the United States are
      suboptimal, which creates an unacceptable health disparity between urban patients
      with stroke and their rural counterparts. The existing gap between urban and
      rural stroke care may widen in the future as more urban-tested interventions are
      incorporated into the treatment of acute stroke. We conducted a PubMed search to
      identify all the articles published from 1997 to 2007 that addressed acute
      stroke, paramedics, ambulances, emergency services, and interhospital
      transportation pertaining to the US rural, urban, or nonurban environment. We
      review herein the problems and potential solutions that exist in 3 aspects of the
      current rural stroke care system: prehospital care, rural local hospital
      emergency department care, and interhospital transfer of patients and subsequent
      reception at a larger tertiary care institution, which often involve long
      distances and considerable time. We conclude that the current gap in rural-urban
      stroke management practices could be overcome with a comprehensive strategy that
      addresses the existing issues, including further education of rural caregivers,
      remote support from tertiary care institutions, and implementation of future
      acute clinical trials that test the rural strategies to stroke care.

PMID- 18625856
TI  - Distinct pools of beta-amyloid in Alzheimer disease-affected brain: a
      clinicopathologic study.
AB  - OBJECTIVE: To determine whether beta-amyloid (Abeta) peptides segregated into
      distinct biochemical compartments would differentially correlate with clinical
      severity of Alzheimer disease (AD). DESIGN: Clinicopathologic correlation study.
      PARTICIPANTS: Twenty-seven patients from a longitudinal study of AD and 13 age-
      and sex-matched controls without a known history of cognitive impairment or
      dementia were included in this study. INTERVENTIONS: Temporal and cingulate
      neocortex were processed using a 4-step extraction, yielding biochemical
      fractions that are hypothesized to be enriched with proteins from distinct
      anatomical compartments: TRIS (extracellular soluble), Triton (intracellular
      soluble), sodium dodecyl sulfate (SDS) (membrane associated), and formic acid
      (extracellular insoluble). Levels of Abeta(40) and Abeta(42) were quantified in
      each biochemical compartment by enzyme-linked immunosorbent assay. RESULTS: The
      Abeta(42) level in all biochemical compartments was significantly elevated in
      patients with AD vs controls (P < .01). The Abeta(40) levels in the TRIS and
      formic acid fractions were elevated in patients with AD (temporal, P < .01;
      cingulate, P = .03); however, Triton and SDS Abeta(40) levels were similar in
      patients with AD and in controls. Functional impairment proximal to death
      correlated with Triton Abeta(42) (r = 0.48, P = .02) and SDS Abeta(42) (r = 0.41,
      P = .04) in the temporal cortex. Faster cognitive decline was associated with
      elevated temporal SDS Abeta(42) levels (P < .001), whereas slower decline was
      associated with elevated cingulate formic acid Abeta(42) and SDS Abeta(42) levels
      (P = .02 and P = .01, respectively). CONCLUSION: Intracellular and membrane
      associated Abeta, especially Abeta(42) in the temporal neocortex, may be more
      closely related to AD symptoms than other measured Abeta species.

PMID- 18625857
TI  - Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive
      transverse myelitis.
AB  - BACKGROUND: There is increasing recognition of antibody-mediated immunotherapy
      responsive neurologic diseases and a need for appropriate immunoassays.
      OBJECTIVES: To develop a clinically applicable quantitative assay to detect the
      presence of aquaporin-4 (AQP4) antibodies in patients with neuromyelitis optica
      and to characterize the anti-AQP4 antibodies. DESIGN: We compared a simple new
      quantitative fluorescence immunoprecipitation assay (FIPA) with both indirect
      immunofluorescence and an AQP4-transfected cell-based assay, both previously
      described. We used the cell-based assay to characterize the antibodies for their
      immunoglobulin class, IgG subclass, and ability to induce complement C3b
      deposition in vitro. SETTING: United Kingdom and Germany. PARTICIPANTS: Serum
      samples from patients with neuromyelitis optica (n = 25) or longitudinally
      extensive transverse myelitis (n = 11) and from relevant controls (n = 78) were
      studied. MAIN OUTCOME MEASURES: Comparison of different assays for AQP4
      antibodies and characterization of anti-AQP4 antibodies in patients with
      neuromyelitis optica. RESULTS: We found antibodies to AQP4 in 19 of 25 patients
      with neuromyelitis optica (76%) using FIPA, in 20 of 25 patients with
      neuromyelitis optica (80%) using the cell-based assay, and in 6 of 11 patients
      with longitudinally extensive transverse myelitis (55%) with both assays; these
      assays were more sensitive than indirect immunofluorescence and 100% specific.
      The antibodies bound to extracellular epitope(s) of AQP4, were predominantly
      IgG1, and strongly induced C3b deposition. CONCLUSIONS: Aquaporin-4 is a major
      antigen in neuromyelitis optica, and antibodies can be detected in more than 75%
      of patients. Further studies on larger samples will show whether this novel FIPA
      is suitable for clinical use. The IgG1 antibodies bind to AQP4 on the cell
      surface and can initiate complement deposition. These approaches will be useful
      for investigation of other antibody-mediated diseases.

PMID- 18625858
TI  - Optical coherence tomography in neuromyelitis optica.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory disease with combined
      features of optic neuritis and myelitis. This pathologic entity may induce severe
      disability, including visual loss and paraplegia. Other than clinical follow-up,
      there is no marker for severity of the disease. OBJECTIVES: To evaluate the use
      of optical coherence tomography (OCT) in NMO and to determine whether this new
      technique could be a good marker of axonal loss in NMO. DESIGN: Cross-sectional
      study. PARTICIPANTS: Thirty-five patients with NMO or at a high risk for NMO
      (having optic neuritis or myelitis and who are positive for NMO antibody) were
      prospectively studied. Fifteen healthy individuals served as control subjects.
      MAIN OUTCOME MEASURE: All patients underwent a complete ophthalmologic
      evaluation, including OCT, funduscopy, and visual field, visual acuity, and
      visual evoked potential testing. Expanded Disability Status Scale scores were
      assessed but without the visual data. Correlations between the visual test
      results and demographic or clinical characteristics were evaluated. RESULTS:
      Optical coherence tomography and visual field data were available for only 32
      patients because 3 patients were blind. The mean retinal nerve fiber layer
      thickness was significantly reduced in patients with NMO compared with controls
      (P < .001). We found good correlation between the OCT results and visual field
      testing. We also found weak correlation between OCT results and both visual
      acuity and visual evoked potential latencies. We did not find any correlation
      between OCT results and age, sex, or disease duration. In contrast, retinal nerve
      fiber layer thickness was closely correlated with the Expanded Disability Status
      Scale score (P < .001). CONCLUSIONS: Optical coherence tomography results are
      significantly altered in patients with NMO. Optical coherence tomography is easy
      to perform, and the results are well correlated with visual acuity and visual
      field findings. It could be considered a marker of axonal loss because we found
      good correlation between OCT and the Expanded Disability Status Scale score.
      These preliminary results will need to be confirmed in a longitudinal prospective
      study.

PMID- 18625859
TI  - Retinal imaging by laser polarimetry and optical coherence tomography evidence of
      axonal degeneration in multiple sclerosis.
AB  - BACKGROUND: Optical coherence tomography (OCT) and scanning laser polarimetry
      with variable corneal compensation (GDx) are similar yet provide information on
      different aspects of retinal nerve fiber layer (RNFL) structure (thickness values
      similar to histology for OCT vs birefringence of microtubules for GDx).
      OBJECTIVES: To compare the ability of OCT and GDx to distinguish eyes of patients
      with multiple sclerosis (MS) from eyes of disease-free controls and thus identify
      RNFL abnormalities. We also sought to examine the capacity of these techniques to
      distinguish MS eyes from those without a history of optic neuritis and to
      correlate with visual function. DESIGN: Cross-sectional study. SETTING: Academic
      tertiary care MS center. PARTICIPANTS: Eighty patients with MS (155 eyes) and 43
      disease-free controls (85 eyes) underwent both OCT and GDx imaging using
      protocols that measure RNFL thickness. MAIN OUTCOME MEASURES: Areas under the
      curve (AUC), adjusted for within-patient, intereye correlations, were used to
      compare the abilities of OCT and GDx temporal-superior-nasal-inferior-temporal
      average RNFL thicknesses to discriminate between MS and control eyes and to
      distinguish MS eyes with a history of optic neuritis. Visual function was
      evaluated using low-contrast letter acuity and high-contrast visual acuity.
      RESULTS: Average peripapillary RNFL thickness (360 degrees around the optic disc)
      was reduced in patients with MS compared with controls for both methods. Age
      adjusted AUC did not differ between OCT (0.80; 95% confidence interval [CI], 0.72
      0.88) and GDx (0.78; 95% CI, 0.68-0.86; P = .38). Optical coherence tomography
      measured RNFL thickness was somewhat better at distinguishing MS eyes with a
      history of optic neuritis from those without (OCT: AUC, 0.73; 95% CI, 0.64-0.82;
      GDx: AUC, 0.66; 95% CI, 0.57-0.66; P = .17). Linear correlations of RNFL
      thickness for OCT vs GDx were significant yet moderate (r = 0.67, P < .001); RNFL
      thickness measures correlated moderately and significantly with low-contrast
      acuity (OCT: r = 0.54, P < .001; GDx: r = 0.55, P < .001) and correlated less
      with high-contrast visual acuity (OCT: r = 0.44, P < .001; GDx: r = 0.32, P <
      .001). CONCLUSIONS: Scanning laser polarimetry with variable corneal compensation
      measurements of RNFL thickness corroborates OCT evidence of visual pathway axonal
      loss in MS and provides new insight into structural aspects of axonal loss that
      relate to RNFL birefringence (microtubule integrity). These results support
      validity for RNFL thickness as a marker for axonal degeneration and support use
      of these techniques in clinical trials that examine neuroprotective and other
      disease-modifying therapies.

PMID- 18625860
TI  - Predictors of extubation failure in myasthenic crisis.
AB  - BACKGROUND: The ideal timing for extubation of patients with myasthenic crisis
      (MC) and the factors that influence extubation outcome are not well established.
      OBJECTIVES: To assess the risk of extubation failure in MC and to identify
      predictors of extubation failure. DESIGN: We reviewed consecutive episodes of MC
      treated with endotracheal intubation from January 1, 1987, through December 31,
      2006. SETTING: Mayo Clinic. Patients Forty patients with 46 episodes of MC
      underwent endotracheal intubation and mechanical ventilation. MAIN OUTCOME
      MEASURES: The main outcome measures were extubation failure and reintubation.
      Extubation failure was defined as reintubation, tracheostomy, or death while
      intubated. Reintubation was also analyzed as a separate end point. Univariate
      logistic regression was used to identify predictors of extubation failure and
      reintubation. RESULTS: Of the 46 episodes of MC, extubation failure occurred in
      20 (44%), including 9 of 35 episodes (26%) of reintubation. Male sex, history of
      previous crisis, atelectasis, and intubation for more than 10 days were
      associated with extubation failure. Lower pH and lower forced vital capacity on
      the time of extubation, atelectasis, and bilevel intermittent positive airway
      pressure use after extubation predicted the need for reintubation. Atelectasis
      showed the strongest association with both end points. Extubation failure and
      reintubation were associated with significant prolongation in intensive care unit
      and hospital length of stay. CONCLUSIONS: Extubation failure is relatively common
      in patients with MC. Atelectasis is the strongest predictor of this complication.

PMID- 18625861
TI  - Impairment in glomerular filtration rate or glomerular filtration barrier and
      occurrence of stroke.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with substantial burden
      and is a strong risk factor for cardiovascular disease. However, data on the
      relationship between CKD and stroke are few and are limited by unreliable or
      inadequate assessment of renal function. OBJECTIVE: To properly assess the
      relationship between renal insufficiency and stroke in stroke survivors in the
      United States by simultaneously examining the effect of guideline-recommended
      indices of renal disease that measure glomerular filtration rate (creatinine
      clearance) and glomerular filtration barrier (proteinuria). DESIGN: Cross
      sectional. SETTING: Nationally representative survey of the United States.
      SUBJECTS: Participants aged 55 or older who participated in the National Health
      and Nutrition Examination Survey from 1999 to 2004. MAIN OUTCOME MEASURES:
      Indices of renal disease that measure glomerular filtration rate (creatinine
      clearance) and glomerular filtration barrier (microalbuminuria). RESULTS: Of 6382
      adults who met inclusion criteria, 5624 (88%) had full and complete data, of
      which 414 (6%) reported having had a stroke. Stroke survivors were older and more
      likely to have CKD, diabetes, hypertension, coronary artery disease, elevated
      blood pressure, increased glycohemoglobin concentration, and lower hematocrit
      compared with respondents who did not report stroke. Multivariate models showed
      that microalbuminuria (odds ratio, 1.51; 95% confidence interval, 1.02-2.24),
      decreased glomerular filtration rate (odds ratio, 1.93; 95% confidence interval,
      1.28-2.91), and stage 3 CKD (odds ratio, 2.09; 95% confidence interval, 1.38
      3.16) were significantly associated with stroke. CONCLUSION: Stroke is
      independently associated with impairment in structure and function of the
      glomerulus, which supports the need to consider screening patients with stroke
      for CKD and to simultaneously assess for both indices of renal disease.

PMID- 18625862
TI  - A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral
      temporal epilepsy.
AB  - BACKGROUND: Mutations responsible for autosomal dominant lateral temporal
      epilepsy have been found in the leucine-rich, glioma-inactivated 1 (LGI1) gene.
      OBJECTIVES: To describe the clinical and genetic findings in a family with
      autosomal dominant lateral temporal epilepsy and to determine the functional
      effects of a novel LGI1 mutation in culture cells. DESIGN: Clinical, genetic, and
      functional investigations. SETTING: University hospital and laboratory. PATIENTS:
      An Italian family with autosomal dominant lateral temporal epilepsy. MAIN OUTCOME
      MEASURE: Mutation analysis. RESULTS: A novel LGI1 mutation, c.365T>A (Ile122Lys),
      segregating with the disease was identified. The mutant Lgi1 protein was not
      secreted by culture cells. CONCLUSION: Our data provide further evidence that
      mutations in LGI1 hamper secretion of the Lgi1 protein, thereby precluding its
      normal function.

PMID- 18625863
TI  - A novel locus for generalized epilepsy with febrile seizures plus in French
      families.
AB  - BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a
      familial autosomal dominant entity characterized by the association of febrile
      and afebrile seizures. Mutations in 3 genes--the sodium channel alpha1 subunit
      gene (SCN1A), the sodium channel beta1 subunit gene (SCN1B), and the gamma2 GABA
      receptor subunit gene (GABRG2)--and linkage to 2 other loci on 2p24 and 21q22
      have been identified in families with GEFS(+), indicating genetic heterogeneity.
      OBJECTIVES: To localize by means of linkage analysis a new gene for GEFS(+) in a
      large family with 11 affected members and to test the new locus in 4 additional
      families with GEFS(+). DESIGN: Family-based linkage analysis. SETTING: University
      hospital. PATIENTS: Five French families with GEFS(+) and at least 7 available
      affected members with autosomal dominant transmission. All the patients had
      febrile seizures and/or afebrile generalized tonic-clonic seizures or absence
      epilepsy. MAIN OUTCOME MEASURES: We analyzed 380 microsatellite markers and
      conducted linkage analysis. RESULTS: In the largest family, a 10-cM-density
      genomewide scan revealed linkage to a 13-Mb (megabase) interval on chromosome
      8p23-p21 with a maximum pairwise logarithm of odds (LOD) score of 3.00 (at Theta
      = 0) for markers D8S351 and D8S550 and a multipoint LOD score of 3.23. A second
      family with GEFS(+) was also possibly linked to chromosome 8p23-p21 and the
      region was narrowed to a 7.3-Mb candidate interval, flanked by markers D8S1706
      and D8S549. We have not, so far, identified mutations in the coding exons of 6
      candidate genes (MTMR9, MTMR7, CTSB, SGCZ, SG223, and ATP6V1B2) located in the
      genetic interval. CONCLUSIONS: We report a sixth locus for GEFS(+) on chromosome
      8p23-p21. Because no ion channel genes are located in this interval,
      identification of the responsible gene will probably uncover a new mechanism of
      pathogenesis for GEFS(+).

PMID- 18625864
TI  - Internal pallidal and thalamic stimulation in patients with Tourette syndrome.
AB  - BACKGROUND: Tourette syndrome (TS) is thought to result from dysfunction of the
      associative-limbic territories of the basal ganglia, and patients with severe
      symptoms of TS respond poorly to medication. High-frequency stimulation has
      recently been applied to patients with TS in open studies using the centromedian
      parafascicular complex (CM-Pf) of the thalamus, the internal globus pallidus
      (GPi), or the anterior limb of the internal capsule as the principal target.
      OBJECTIVE: To report the effect of high-frequency stimulation of the CM-Pf and/or
      the GPi, 2 associative-limbic relays of the basal ganglia, in patients with TS.
      DESIGN: Controlled, double-blind, randomized crossover study. SETTING: Medical
      research. PATIENTS: Three patients with severe and medically refractory TS.
      INTERVENTION: Bilateral placement of stimulating electrodes in the CM-Pf
      (associative-limbic part of the thalamus) and the GPi (ventromedial part). MAIN
      OUTCOME MEASURES: Effects of thalamic, pallidal, simultaneous thalamic and
      pallidal, and sham stimulation on neurologic, neuropsychological, and psychiatric
      symptoms. RESULTS: A dramatic improvement on the Yale Global Tic Severity Scale
      was obtained with bilateral stimulation of the GPi (reduction in tic severity of
      65%, 96%, and 74% in patients 1, 2, and 3, respectively). Bilateral stimulation
      of the CM-Pf produced a 64%, 30%, and 40% reduction in tic severity,
      respectively. The association of thalamic and pallidal stimulation showed no
      further reduction in tic severity (60%, 43%, and 76%), whereas motor symptoms
      recurred during the sham condition. No neuropsychological, psychiatric, or other
      long-term adverse effect was observed. CONCLUSIONS: High-frequency stimulation of
      the associative-limbic relay within the basal ganglia circuitry may be an
      effective treatment of patients with TS, thus heightening the hypothesis of a
      dysfunction in these structures in the pathophysiologic mechanism of the
      disorder.

PMID- 18625865
TI  - Clinical and molecular findings of ataxia with oculomotor apraxia type 2 in 4
      families.
AB  - BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal
      recessive disease caused by SETX mutations in 9q34 resulting in cerebellar ataxia
      in association with peripheral neuropathy, cerebellar atrophy on imaging, an
      elevated alpha-fetoprotein (AFP) serum level, and occasional oculomotor apraxia.
      OBJECTIVE: To describe the clinical and molecular findings of 7 patients with a
      clinical presentation of AOA2 and their relatives. DESIGN: Case report. SETTING:
      Projet Hospitalier de Recherche Clinique. PATIENTS: Seven patients with AOA2 and
      their family members. INTERVENTION: Linkage analysis and direct sequencing of all
      exons of SETX were performed in all patients. Magnetic resonance imaging and
      electroneuromyography were performed and the patients' AFP serum levels were
      tested. RESULTS: We identified 7 patients with AOA2 from 4 unrelated families.
      Three novel SETX mutations were found. The clinical picture of the patients
      reported is fairly homogeneous and in accordance with the classic AOA2
      presentation: onset from 13 to 18 years of progressive cerebellar ataxia and
      areflexia. Oculomotor apraxia was detected in 1 patient. Predominant axonal
      neuropathy and a diffuse cerebellar atrophy were found in the 4 patients tested.
      All patients had elevated AFP serum levels and 5 of 8 nonsymptomatic heterozygous
      relatives had moderately increased AFP serum levels as well. CONCLUSIONS: Ataxia
      with oculomotor apraxia type 2 is a homogeneous form of cerebellar ataxia with
      occasional oculomotor apraxia. Most nonsymptomatic heterozygous carriers present
      with increased AFP serum levels.

PMID- 18625866
TI  - Detecting dementia with the mini-mental state examination in highly educated
      individuals.
AB  - OBJECTIVE: To evaluate the utility of Mini-Mental State Examination (MMSE) scores
      in detecting cognitive dysfunction in a sample of highly educated individuals.
      DESIGN: Archival data were reviewed on 4248 participants enrolled in the Mayo
      Clinic Alzheimer Disease Research Center and Alzheimer Disease Patient Registry.
      PATIENTS: A total of 1141 primarily white (93%) individuals with 16 or more years
      of self-reported education were identified. These included 307 (164 men and 143
      women) patients with dementia (any type), 176 (106 men and 70 women) patients
      with mild cognitive impairment, and 658 (242 men and 416 women) control
      participants without dementia. SETTING: Mayo Clinic Alzheimer Disease Research
      Center and Alzheimer Disease Patient Registry cohort. MAIN OUTCOME MEASURES:
      Diagnostic accuracy estimates (sensitivity, specificity, and positive and
      negative predictive power) of MMSE cut scores in detecting cognitive dysfunction.
      RESULTS: In this sample of highly educated, largely white older adults, the
      standard MMSE cut score of 24 (23 or below) yielded a sensitivity of 0.66, a
      specificity of 0.99, and an overall correct classification rate of 89% in
      detecting dementia. A cut score of up to 27 (26 or below) resulted in an optimal
      balance of sensitivity and specificity (0.89 and 0.91, respectively) with an
      overall correct classification rate of 90%. In a cognitively impaired group
      (dementia and mild cognitive impairment), a cut score of 27 (sensitivity, 0.69;
      specificity, 0.91) or 28 (sensitivity and specificity, 0.78) might be more
      appropriate. CONCLUSION: Older patients with a college education who present with
      complaints of cognitive decline (reported by themselves or others) and score less
      than 27 on the MMSE are at a greater risk of being diagnosed with dementia and
      should be referred for a comprehensive dementia evaluation, including formal
      neuropsychological testing.

PMID- 18625867
TI  - Lewis-Sumner syndrome and Tangier disease.
AB  - OBJECTIVE: To report unusual electrophysiologic data in a patient with Tangier
      disease in an effort to better understand the pathophysiologic features of the
      peripheral nerve lesions in this disease. DESIGN: Case report. PATIENT: A 15-year
      old girl had subacute onset of asymmetric neuropathy with persistent conduction
      block, resembling Lewis-Sumner syndrome. MAIN OUTCOME MEASURES:
      Electrophysiologic data in Tangier disease. RESULTS: After initially unsuccessful
      treatment with intravenously administered immunoglobulins, the finding of an
      abnormal lipid profile led to the diagnosis of Tangier disease due to the R587W
      mutation in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1)
      (OMIM 9q22-q31). CONCLUSIONS: Conduction block, which is the electrophysiologic
      hallmark of focal demyelination, can be present in Tangier disease. It could be
      induced by focal nerve ischemia or by preferential lipid deposition in the
      paranodal regions of myelinated Schwann cells. The presence of a conduction block
      in Tangier disease may lead to a misdiagnosis of dysimmune neuropathy.

PMID- 18625868
TI  - Sporadic fatal insomnia masquerading as a paraneoplastic cerebellar syndrome.
AB  - BACKGROUND: Sporadic fatal insomnia is a rare prion disease that has recently
      been recognized. OBJECTIVE: To report a unique case of sporadic fatal insomnia in
      a woman with progressive cerebellar deterioration who was originally thought to
      have a paraneoplastic cerebellar syndrome. DESIGN: Case report describing a
      patient with autopsy-proven sporadic fatal insomnia. PATIENT: A 56-year-old woman
      with progressive cerebellar ataxia who was found to have a retroperitoneal non
      Hodgkin lymphoma. RESULTS: Autopsy demonstrated marked degenerative changes in
      the thalamus, cerebellum, and inferior olivary nucleus. A mild spongiform change
      was present in the thalamus and cortical gray matter. Western blot analysis
      confirmed the presence of abnormal, protease-resistant prion protein (PrP(Sc)),
      characteristic of sporadic fatal insomnia. CONCLUSIONS: Clinicians should be
      aware of this rare prion disease and should strongly consider the importance of
      autopsy toward the investigation of unusual neurological diseases.

PMID- 18625869
TI  - Ultra-early magnetic resonance imaging findings of eclampsia.
AB  - OBJECTIVE: To report the very early magnetic resonance imaging features of
      eclampsia. DESIGN: Case report. SETTING: Inpatient neurology service. PATIENT: A
      35-year-old woman who developed late postpartum eclampsia with cerebral edema,
      caudate hemorrhage, and ischemic strokes. Main Outcome Measure Very early
      magnetic resonance imaging features. RESULTS: Magnetic resonance imaging with
      gadolinium showed posterior sulcal hyperintensity and leptomeningeal enhancement
      preceding the development of posterior reversible encephalopathy syndrome,
      hemorrhage, and ischemic strokes by days. CONCLUSION: Magnetic resonance imaging
      with gadolinium shows early characteristic findings that precede the more classic
      clinical presentation of eclampsia.

PMID- 18625870
TI  - Isolated facial sensory loss in stroke restricted to the ventroposteromedial
      nucleus.

PMID- 18625871
TI  - Primary brain amyloidoma: long-term follow-up.

PMID- 18625872
TI  - Spinal cavernous angiolipoma.

PMID- 18625873
TI  - Brain manganese deposition depicted by magnetic resonance imaging in a welder.

PMID- 18625874
TI  - Sinus thrombosis should be treated with anticoagulation.

PMID- 18625875
TI  - Anticoagulation in cerebral venous sinus thrombosis: are we treating ourselves?

PMID- 18625876
TI  - Cerebral venous sinus thrombosis: to treat or not to treat?

PMID- 18625877
TI  - Hypertension and mild cognitive impairment subtypes.

PMID- 18625878
TI  - Notice of failure to disclose financial interest: "A neuropsychological test
      battery for use in Alzheimer disease clinical trials" (Arch Neurol.
      2007;64[9]:1323-1329).

PMID- 18625879
TI  - Unreported financial disclosures.

PMID- 18625880
TI  - Antihypertensive medications influence the rate of conversion from mild cognitive
      impairment to Alzheimer disease.

PMID- 18625881
TI  - Neuromyelitis optica and autoimmune diseases.

PMID- 18625882
TI  - Neuromyelitis optica with coexisting autoimmune disorders.

PMID- 18625883
TI  - Graft rejection as a Th1-type process amenable to regulation by donor Th2-type
      cells through an interleukin-4/STAT6 pathway.
AB  - Graft rejection has been defined as the mirror image of graft-versus-host
      disease, which is biologically characterized primarily as a Th1-type process. As
      such, we reasoned that graft rejection would represent a Th1 response amenable to
      Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated
      rejection of fully MHC-disparate murine bone marrow allografts more effectively
      than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not
      differentiate into Th1-type cells in vivo and failed to mediate rejection. We
      next hypothesized that donor Th2 cell allograft augmentation would prevent
      rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2
      cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity,
      persisted posttransplantation, and did not mediate rejection. Abrogation of
      rejection required donor Th2 cell IL-4 secretion and host T-cell STAT6 signaling.
      In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1
      type process that can be abrogated by donor Th2 cell therapy that promotes
      engraftment through a novel mechanism whereby cytokine polarization is
      transferred to host T cells.

PMID- 18625884
TI  - A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell
      migration.
AB  - The capacity of dendritic cells (DCs) to migrate from peripheral organs to lymph
      nodes (LNs) is important in the initiation of a T cell-mediated immune response.
      The ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the
      multidrug resistance protein 1 (MRP1; ABCC1) have been shown to play a role in
      both human and murine DC migration. Here we show that a more recently discovered
      family member, MRP4 (ABCC4), is expressed on both epidermal and dermal human skin
      DCs and contributes to the migratory capacity of DCs. Pharmacological inhibition
      of MRP4 activity or down-regulation through RNAi in DCs resulted in reduced
      migration of DCs from human skin explants and of in vitro generated Langerhans
      cells. The responsible MRP4 substrate remains to be identified as exogenous
      addition of MRP4's known substrates prostaglandin E(2), leukotriene B(4) and
      D(4), or cyclic nucleotides (all previously implicated in DC migration) could not
      restore migration. This notwithstanding, our data show that MRP4 is an important
      protein, significantly contributing to human DC migration toward the draining
      lymph nodes, and therefore relevant for the initiation of an immune response and
      a possible target for immunotherapy.

PMID- 18625885
TI  - Igbp1 is part of a positive feedback loop in stem cell factor-dependent,
      selective mRNA translation initiation inhibiting erythroid differentiation.
AB  - Stem cell factor (SCF)-induced activation of phosphoinositide-3-kinase (PI3K) is
      required for transient amplification of the erythroblast compartment. PI3K
      stimulates the activation of mTOR (target of rapamycin) and subsequent release of
      the cap-binding translation initiation factor 4E (eIF4E) from the 4E-binding
      protein 4EBP, which controls the recruitment of structured mRNAs to polysomes.
      Enhanced expression of eIF4E renders proliferation of erythroblasts independent
      of PI3K. To investigate which mRNAs are selectively recruited to polysomes, we
      compared SCF-dependent gene expression between total and polysome-bound mRNA.
      This identified 111 genes primarily subject to translational regulation. For 8 of
      9 genes studied in more detail, the SCF-induced polysome recruitment of
      transcripts exceeded 5-fold regulation and was PI3K-dependent and eIF4E
      sensitive, whereas total mRNA was not affected by signal transduction. One of the
      targets, Immunoglobulin binding protein 1 (Igbp1), is a regulatory subunit of
      protein phosphatase 2A (Pp2a) sustaining mTOR signaling. Constitutive expression
      of Igbp1 impaired erythroid differentiation, maintained 4EBP and p70S6k
      phosphorylation, and enhanced polysome recruitment of multiple eIF4E-sensitive
      mRNAs. Thus, PI3K-dependent polysome recruitment of Igbp1 acts as a positive
      feedback mechanism on translation initiation underscoring the important
      regulatory role of selective mRNA recruitment to polysomes in the balance between
      proliferation and maturation of erythroblasts.

PMID- 18625886
TI  - Long-term progression-free survival of mantle cell lymphoma after intensive front
      line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized
      phase 2 multicenter study by the Nordic Lymphoma Group.
AB  - Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy
      with stem cell support has not been tested in large, prospective series. In the
      2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than
      66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy
      with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi
      CHOP), alternating with R + high-dose cytarabine. Responders received high-dose
      chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and
      melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support.
      Overall and complete response was achieved in 96% and 54%, respectively. The 6
      year overall, event-free, and progression-free survival were 70%, 56%, and 66%,
      respectively, with no relapses occurring after 5 years. Multivariate analysis
      showed Ki-67 to be the sole independent predictor of event-free survival. The
      nonrelapse mortality was 5%. The majority of stem cell products and patients
      assessed with polymerase chain reaction (PCR) after transplantation were
      negative. Compared with our historical control, the Nordic MCL-1 trial, the event
      free, overall, and progression-free survival, the duration of molecular
      remission, and the proportion of PCR-negative stem cell products were
      significantly increased (P < .001). Intensive immunochemotherapy with in vivo
      purged stem cell support can lead to long-term progression-free survival of MCL
      and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.

PMID- 18625887
TI  - Characterization of megakaryocyte GATA1-interacting proteins: the corepressor
      ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation.
AB  - The transcription factor GATA1 coordinates timely activation and repression of
      megakaryocyte gene expression. Loss of GATA1 function results in excessive
      megakaryocyte proliferation and disordered terminal platelet maturation, leading
      to thrombocytopenia and leukemia in patients. The mechanisms by which GATA1 does
      this are unclear. We have used in vivo biotinylated GATA1 to isolate
      megakaryocyte GATA1-partner proteins. Here, several independent approaches show
      that GATA1 interacts with several proteins in the megakaryocyte cell line L8057
      and in primary megakaryocytes. They include FOG1, the NURD complex, the
      pentameric complex containing SCL/TAL-1, the zinc-finger regulators GFI1B and
      ZFP143, and the corepressor ETO2. Knockdown of ETO2 expression promotes
      megakaryocyte differentiation and enhances expression of select genes expressed
      in terminal megakaryocyte maturation, eg, platelet factor 4 (Pf4). ETO2-dependent
      direct repression of the Pf4 proximal promoter is mediated by GATA-binding sites
      and an E-Box motif. Consistent with this, endogenous ETO2, GATA1, and the SCL
      pentameric complex all specifically bind the promoter in vivo. Finally, as ETO2
      expression is restricted to immature megakaryocytes, these data suggest that ETO2
      directly represses inappropriate early expression of a subset of terminally
      expressed megakaryocyte genes by binding to GATA1 and SCL.

PMID- 18625888
TI  - Lymphoid-affiliated genes are associated with active histone modifications in
      human hematopoietic stem cells.
AB  - To address the role of chromatin structure in the establishment of hematopoietic
      stem cell (HSC) multilineage potential and commitment to the lymphoid lineage, we
      have analyzed histone modifications at a panel of lymphoid- and myeloid
      affiliated genes in multipotent and lineage-committed hematopoietic cells
      isolated from human cord blood. Our results show that many B- and T-lymphoid
      genes, although silent in HSCs, are associated with acetylated histones H3 and
      H4. We also detected histone H3 lysine 4 methylation but not repressive lysine 9
      or 27 methylation marks at these loci, indicative of an open chromatin structure.
      Interestingly, the relative level of H3 lysine 4 dimethylation to trimethylation
      at B-specific loci was high in multipotent CD34(+)CD38(lo) progenitors and
      decreased as they become actively transcribed in B-lineage cells. In vitro
      differentiation of CD34(+) cells toward the erythroid, granulocyte, and T-cell
      lineages resulted in a loss of histone acetylation at nonlineage-associated
      genes. This study provides evidence that histone modifications involved in
      chromatin decondensation are already in place at lymphoid-specific genes in
      primary human HSCs, supporting the idea that these genes are "primed" for
      expression before lineage commitment. This permissive chromatin structure is
      progressively lost as the stem cell differentiates.

PMID- 18625889
TI  - Shift work is a risk factor for increased blood pressure in Japanese men: a 14
      year historical cohort study.
AB  - To clarify the effect of shift work on blood pressure in Japanese men, a 14-year
      historical cohort study was conducted in day workers (n=3963) and alternating
      shift workers (n=2748) who received annual health checkups between 1991 and 2005
      in a Japanese steel company. The end points were a >or=10%, >or=15%, >or=20%,
      >or=25%, or >or=30% increase in systolic blood pressure or diastolic blood
      pressure from baseline during the period of observation. The association between
      shift work and an increase in blood pressure was investigated adjusting for age,
      body mass index, hemoglobin A1c, total serum cholesterol, creatinine, aspartate
      aminotransferase, gamma-glutamyl transpeptidase, uric acid, drinking habit,
      smoking habit, and habitual exercise by multivariate pooled logistic regression
      analyses. Shift work was significantly associated with the various end points.
      The odds ratios (and 95% CIs) were as follows: >or=10%, 1.15 (1.07 to 1.23);
      >or=15%, 1.21 (1.12 to 1.31); >or=20%, 1.15 (1.04 to 1.28); >or=25%, 1.20 (1.06
      to 1.37); and >or=30%, 1.23 (1.03 to 1.47) for systolic blood pressure and
      >or=10%, 1.19 (1.11 to 1.28); >or=15%, 1.22 (1.13 to 1.33); >or=20%, 1.24 (1.13
      to 1.37); and >or=25%, 1.16 (1.03 to 1.30) for diastolic blood pressure. Our
      study in male Japanese workers revealed that alternating shift work was a
      significant independent risk factor for an increase in blood pressure. Moreover,
      the effect of shift work on blood pressure was more pronounced than other well
      established factors, such as age and body mass index.

PMID- 18625890
TI  - Generation of functional murine cardiac myocytes from induced pluripotent stem
      cells.
AB  - BACKGROUND: The recent breakthrough in the generation of induced pluripotent stem
      (iPS) cells, which are almost indistinguishable from embryonic stem (ES) cells,
      facilitates the generation of murine disease- and human patient-specific stem
      cell lines. The aim of this study was to characterize the cardiac differentiation
      potential of a murine iPS cell clone in comparison to a well-established murine
      ES cell line. METHODS AND RESULTS: With the use of a standard embryoid body-based
      differentiation protocol for ES cells, iPS cells as well as ES cells were
      differentiated for 24 days. Although the analyzed iPS cell clone showed a delayed
      and less efficient formation of beating embryoid bodies compared with the ES cell
      line, the differentiation resulted in an average of 55% of spontaneously
      contracting iPS cell embryoid bodies. Analyses on molecular, structural, and
      functional levels demonstrated that iPS cell-derived cardiomyocytes show typical
      features of ES cell-derived cardiomyocytes. Reverse transcription polymerase
      chain reaction analyses demonstrated expression of marker genes typical for
      mesoderm, cardiac mesoderm, and cardiomyocytes including Brachyury, mesoderm
      posterior factor 1 (Mesp1), friend of GATA2 (FOG-2), GATA-binding protein 4
      (GATA4), NK2 transcription factor related, locus 5 (Nkx2.5), T-box 5 (Tbx5), T
      box 20 (Tbx20), atrial natriuretic factor (ANF), myosin light chain 2 atrial
      transcripts (MLC2a), myosin light chain 2 ventricular transcripts (MLC2v), alpha
      myosin heavy chain (alpha-MHC), and cardiac troponin T in differentiation
      cultures of iPS cells. Immunocytology confirmed expression of cardiomyocyte
      typical proteins including sarcomeric alpha-actinin, titin, cardiac troponin T,
      MLC2v, and connexin 43. iPS cell cardiomyocytes displayed spontaneous rhythmic
      intracellular Ca(2+) fluctuations with amplitudes of Ca(2+) transients comparable
      to ES cell cardiomyocytes. Simultaneous Ca(2+) release within clusters of iPS
      cell-derived cardiomyocytes indicated functional coupling of the cells.
      Electrophysiological studies with multielectrode arrays demonstrated
      functionality and presence of the beta-adrenergic and muscarinic signaling
      cascade in these cells. CONCLUSIONS: iPS cells differentiate into functional
      cardiomyocytes. In contrast to ES cells, iPS cells allow derivation of autologous
      functional cardiomyocytes for cellular cardiomyoplasty and myocardial tissue
      engineering.

PMID- 18625891
TI  - Directed and systematic differentiation of cardiovascular cells from mouse
      induced pluripotent stem cells.
AB  - BACKGROUND: Induced pluripotent stem (iPS) cells are a novel stem cell population
      induced from mouse and human adult somatic cells through reprogramming by
      transduction of defined transcription factors. However, detailed differentiation
      properties and the directional differentiation system of iPS cells have not been
      demonstrated. METHODS AND RESULTS: Previously, we established a novel mouse
      embryonic stem (ES) cell differentiation system that can reproduce the early
      differentiation processes of cardiovascular cells. We applied our ES cell system
      to iPS cells and examined directional differentiation of mouse iPS cells to
      cardiovascular cells. Flk1 (also designated as vascular endothelial growth factor
      receptor-2)-expressing mesoderm cells were induced from iPS cells after
      approximately 4-day culture for differentiation. Purified Flk1(+) cells gave rise
      to endothelial cells and mural cells by addition of vascular endothelial growth
      factor and serum. Arterial, venous, and lymphatic endothelial cells were also
      successfully induced. Self-beating cardiomyocytes could be induced from Flk1(+)
      cells by culture on OP9 stroma cells. Time course and efficiency of the
      differentiation were comparable to those of mouse ES cells. Occasionally,
      reexpression of transgene mRNAs, including c-myc, was observed in long-term
      differentiation cultures. CONCLUSIONS: Various cardiovascular cells can be
      systematically induced from iPS cells. The differentiation properties of iPS
      cells are almost completely identical to those of ES cells. This system would
      greatly contribute to a novel understanding of iPS cell biology and the
      development of novel cardiovascular regenerative medicine.

PMID- 18625892
TI  - Translating research into practice for healthcare providers: the American Heart
      Association's strategy for building healthier lives, free of cardiovascular
      diseases and stroke.
AB  - The American Heart Association's (AHA's) mission is "to build healthier lives,
      free of cardiovascular diseases and stroke." This first article in a 2-part
      series will serve to present an overview of the work the AHA has undertaken to
      translate evidence into practice for healthcare professionals. It describes the
      extensive work of the AHA to support and further the delivery of evidence-based
      medicine, which includes the following: (1) supporting scientific discovery and
      the next generation of healthcare professionals and researchers; (2)
      disseminating scientific information; (3) developing evidence-based guidelines
      and statements; (4) creating and advocating for the implementation of performance
      indicators/measures; (5) developing clinical decision support and quality
      improvement tools; and (6) developing directed-cause campaigns, all of which can
      lead to improved patient care. This article also discusses the need for novel
      approaches and some of the AHA's evolving strategies to help address gaps in
      care. The second article, which will be published shortly after this one, will
      examine the AHA's efforts to engage and empower healthcare consumers to become
      more involved with their own health and health care.

PMID- 18625893
TI  - Relation between body mass index, waist circumference, and death after acute
      myocardial infarction.
AB  - BACKGROUND: An elevated body mass index (BMI) has been reported to be associated
      with a lower rate of death after acute myocardial infarction (AMI). However,
      waist circumference (WC) may be a better marker of cardiovascular risk than BMI.
      We used data from a contemporary French population-based cohort of patients with
      AMI to analyze the impact of WC and BMI on death rates. METHODS AND RESULTS: We
      evaluated 2229 consecutive patients with AMI. Patients were classified according
      to BMI as normal, overweight, obese, and very obese (BMI <25, 25 to 29.9, 30 to
      34.5, and >35 kg/m(2), respectively) and as increased waistline (WC >88/102 cm
      for women/men) or normal. Half of the patients were overweight (n=1044), and one
      quarter were obese (n=397) or very obese (n=128). Increased WC was present in
      half of the patients (n=1110). Increased BMI was associated with a reduced death
      rate, with a 5% risk reduction for each unit increase in BMI (hazard ratio, 0.95;
      95% CI, 0.93 to 0.98; P<0.001). In contrast, WC as a continuous variable had no
      impact on all-cause death (P=0.20). After adjustment for baseline predictors of
      death, BMI was not independently predictive of death. The group of patients with
      high WC but low BMI had increased 1-year death rate. CONCLUSIONS: Neither BMI nor
      WC independently predicts death after AMI. Much of the inverse relationship
      between BMI and the rate of death after AMI is due to confounding by
      characteristics associated with survival. This study emphasizes the need to
      measure both BMI and WC because patients with a high WC and low BMI are at high
      risk of death.

PMID- 18625894
TI  - Patient-reported health status in coronary heart disease in the United States:
      age, sex, racial, and ethnic differences.
AB  - BACKGROUND: Coronary heart disease (CHD) affects 15.8 million Americans. However,
      data on the national impact of CHD on health-related quality of life,
      particularly among people of different age, sex, racial, and ethnic groups, are
      limited. METHODS AND RESULTS: Using data from the 2000 and 2002 Medical
      Expenditure Panel Survey, we examined various measures of patient-reported health
      status, including health-related quality of life, in the CHD and non-CHD
      populations and differences in the measures among demographic subgroups. These
      measures included short-form generic measures (Short Form 12; Mental Component
      Summary-12 and Physical Component Summary-12) and EuroQol Group measures (EQ-5D
      index and EQ visual analog scale). Ordinary least-squares regressions were used
      to adjust for sociodemographic characteristics, risk factors, comorbidities, and
      proxy report. The adjusted difference between the CHD and non-CHD populations was
      -1.2 for Mental Component Summary-12 (2.4% of the score in the non-CHD
      population), -4.6 for Physical Component Summary-12 (9.2%), -0.04 for EQ-5D
      (4.6%), and -7.3 for EQ visual analog scale (9.0%) (all P<0.05). Differences
      among demographic subgroups were observed. Particularly, compared with whites,
      the differences between CHD and non-CHD in blacks were bigger in all measures
      except Physical Component Summary-12. A significantly bigger difference in Mental
      Component Summary-12 also was observed among Hispanics compared with non
      Hispanics. CONCLUSIONS: CHD is associated with significant impairment of health
      related quality of life and other patient-reported health status in the US adult
      population. Differences in the impairment associated with CHD exist across
      different age, racial, and ethnic groups. In addition to preventing CHD,
      effective public health interventions should be aimed at improving health-related
      quality of life and perceived health status in the CHD population, especially the
      most vulnerable groups.

PMID- 18625895
TI  - Evidence of arteriolar narrowing in low-birth-weight children.
AB  - BACKGROUND: Cardiovascular disease may have its origins in utero, but the
      influence of in utero growth on microvascular structure in children is unknown.
      We hypothesized that poor in utero growth is associated with narrower arteriolar
      caliber, which may help explain the established association of low birth weight
      with hypertension and cardiovascular disease in adulthood. METHODS AND RESULTS:
      We examined the relation of birth weight and other markers of in utero growth to
      microvascular caliber in the retina in a population-based study of 1369 6-year
      old children in Sydney, Australia (Sydney Childhood Eye Study). Birth weight,
      birth length, and head circumference were obtained from parental records. Retinal
      arteriolar and venular calibers were measured from digitized retinal photographs
      by a validated computer-assisted method. Lower birth weight, shorter birth
      length, and smaller head circumference were associated with narrower retinal
      arteriolar caliber. Each kilogram decrease in birth weight was associated with a
      2.3-mum (95% CI 0.6 to 3.9, P=0.01) narrower retinal arteriolar caliber after
      controlling for age, gender, ethnicity, height, body mass index, axial length,
      mean arterial blood pressure, and prematurity. Similar associations were observed
      between shorter birth length and smaller head circumference with narrower retinal
      arteriolar caliber. CONCLUSIONS: Children who had lower birth weight, shorter
      birth length, and smaller head circumference had narrower retinal arteriolar
      calibers. These data support the concept that poor in utero growth may have an
      adverse influence on microvascular structure.

PMID- 18625896
TI  - Does sodium nitroprusside decrease the incidence of atrial fibrillation after
      myocardial revascularization?: a pilot study.
AB  - BACKGROUND: Atrial fibrillation (AF) often occurs after coronary artery bypass
      grafting and can result in increased morbidity and mortality. In the present
      pilot study, our aim was to investigate whether sodium nitroprusside (SNP), as a
      nitric oxide donor, can reduce the frequency of post-coronary artery bypass
      grafting AF. METHODS AND RESULTS: To investigate the effectiveness of SNP in the
      prophylaxis of AF, we conducted a prospective, randomized, placebo-controlled
      clinical study on 100 consecutive patients in whom we performed elective and
      initial CABG operations. A control group of 50 patients were treated with placebo
      (dextrose 5% in water), whereas the SNP group (n=50 patients) was treated with
      SNP (0.5 microg x kg(-1) x min(-1)) during the rewarming period. High-sensitivity
      C-reactive protein levels were measured before surgery and 5 days
      postoperatively. All patients were monitored postoperatively with telemetry.
      Baseline characteristics were similar in both treatment groups. AF occurred in
      12% of the SNP group and 27% of the control group. The occurrence of AF was
      significantly lower in the SNP group (P=0.005). The duration of AF in the SNP
      group was significantly shorter than that in the control group (5.33+/-1.86 and
      7.55+/-1.94 hours, respectively; P=0.023). C-reactive protein levels were higher
      postoperatively in the control group than in the SNP group (P<0.05).
      Postoperative AF significantly prolonged postoperative hospital stay (P<0.05).
      CONCLUSIONS: The incidence of postoperative AF in the SNP group was reduced
      significantly. Further studies are needed to better delineate the anti-AF profile
      of SNP.

PMID- 18625897
TI  - Cardiology patient pages. Postural tachycardia syndrome: perspectives for
      patients.

PMID- 18625898
TI  - Scimitar syndrome: comprehensive, noninvasive assessment with cardiovascular
      magnetic resonance imaging.

PMID- 18625899
TI  - The difficulty of adequate risk stratification for patients with asymptomatic
      diabetes.

PMID- 18625900
TI  - Letter by Pignier and Le Grand regarding article "Acute administration of fish
      oil inhibits triggered activity in isolated myocytes from rabbits and patients
      with heart failure".

PMID- 18625902
TI  - Dietary patterns and longevity: expanding the blue zones.

PMID- 18625903
TI  - Put your chips on transcriptomics.

PMID- 18625904
TI  - Systems of care: need for hub-and-spoke systems for both primary and systematic
      percutaneous coronary intervention after fibrinolysis.

PMID- 18625905
TI  - Myocardial contrast echocardiography: a 25-year retrospective.

PMID- 18625906
TI  - Outcomes research: generating evidence for best practice and policies.

PMID- 18625907
TI  - Sweet heart block.

PMID- 18625908
TI  - Early vertebrate whole genome duplications were predated by a period of intense
      genome rearrangement.
AB  - Researchers, supported by data from polyploid plants, have suggested that whole
      genome duplication (WGD) may induce genomic instability and rearrangement, an
      idea which could have important implications for vertebrate evolution. Benefiting
      from the newly released amphioxus genome sequence (Branchiostoma floridae), an
      invertebrate that researchers have hoped is representative of the ancestral
      chordate genome, we have used gene proximity conservation to estimate rates of
      genome rearrangement throughout vertebrates and some of their invertebrate
      ancestors. We find that, while amphioxus remains the best single source of
      invertebrate information about the early chordate genome, its genome structure is
      not particularly well conserved and it cannot be considered a fossilization of
      the vertebrate preduplication genome. In agreement with previous reports, we
      identify two WGD events in early vertebrates and another in teleost fish.
      However, we find that the early vertebrate WGD events were not followed by
      increased rates of genome rearrangement. Indeed, we measure massive genome
      rearrangement prior to these WGD events. We propose that the vertebrate WGD
      events may have been symptoms of a preexisting predisposition toward genomic
      structural change.

PMID- 18625909
TI  - Live Lactobacillus rhamnosus and Streptococcus pyogenes differentially regulate
      Toll-like receptor (TLR) gene expression in human primary macrophages.
AB  - Macrophages are phagocytes that recognize bacteria and subsequently activate
      appropriate innate and adaptive immune responses. TLRs are essential in
      identifying conserved bacterial structures and in initiating and mediating innate
      immune responses. In this work, we have characterized TLR gene expression in
      human monocyte-derived macrophages in response to stimulation with two live Gram
      positive bacteria, a human commensal and probiotic Lactobacillus rhamnosus GG
      (LGG), and an important human pathogen Streptococcus pyogenes. LGG and S.
      pyogenes enhanced TLR2 expression in macrophages. LGG and S. pyogenes also
      required TLR2 for NF-kappaB activation. Only pathogenic S. pyogenes was able to
      up-regulate TLR3 and TLR7 gene expression. This up-regulation was dependent on
      IFN-alpha/beta, as neutralizing anti-IFN-alpha/beta antibodies reduced S.
      pyogenes-induced TLR3 and TLR7 mRNA expression. Our results show that despite
      similarities, TLR responses of macrophages differ for a Gram-positive probiotic
      and a pathogen. Our data suggest that macrophages can discriminate between
      probiotic and pathogenic bacteria by IFN-mediated TLR gene regulation.

PMID- 18625910
TI  - The nucleotide receptor P2RX7 mediates ATP-induced CREB activation in human and
      murine monocytic cells.
AB  - Nucleotide receptors serve as sensors of extracellular ATP and are important for
      immune function. The nucleotide receptor P2RX7 is a cell-surface, ligand-gated
      cation channel that has been implicated in many diseases, including arthritis,
      granuloma formation, sepsis, and tuberculosis. These disorders are often
      exacerbated by excessive mediator release from activated macrophages in the
      inflammatory microenvironment. Although P2RX7 activation can modulate
      monocyte/macrophage-induced inflammatory events, the relevant molecular
      mechanisms are poorly understood. Previous studies suggest that MAPK cascades and
      transcriptional control via CREB-linked pathways regulate the inflammatory
      capacity of monocytic cells. As P2RX7 promotes MAPK activation and inflammatory
      mediator production, we examined the involvement MAPK-induced CREB activation in
      P2RX7 action. Our data reveal that stimulation of multiple monocytic cell lines
      with P2RX7 agonists induces rapid CREB phosphorylation. In addition, we observed
      a lack of nucleotide-induced CREB phosphorylation in RAW 264.7 cells expressing
      nonfunctional P2RX7 and a gain of nucleotide-induced CREB phosphorylation in
      human embryonic kidney-293 cells that heterologously express human P2RX7.
      Furthermore, our results indicate that P2RX7 agonist-induced CREB phosphorylation
      is partly mediated via Ca(2+) fluxes and the MEK/ERK system. Mechanistic analyses
      revealed that macrophage stimulation with a P2RX7 agonist induces CREB/CREB
      binding protein complex formation, which is necessary for CREB transcriptional
      activation. Also, we demonstrate that P2RX7 activation induces a known CREB
      dependent gene (c-fos) and that dominant-negative CREB constructs attenuate this
      response. These studies support the idea that P2RX7 stimulation can directly
      regulate protein expression that is not dependent on costimulation with other
      immune modulators such as LPS.

PMID- 18625912
TI  - Interactions between Shiga toxins and human polymorphonuclear leukocytes.
AB  - Human intestinal infections by Shiga toxin (Stx)-producing Escherichia coli cause
      hemorrhagic colitis and hemolytic uremic syndrome (HUS), which represents the
      main cause of acute renal failure in early childhood. In HUS, Stx released in the
      gut enter the bloodstream and are targeted to renal endothelium. The mechanism of
      toxin delivery is still a matter of debate, although the role of
      polymorphonuclear leukocytes (PMN) as a Stx carrier has been indicated. The aim
      of this paper was to better define the interactions between Stx and human PMN.
      Direct and indirect flow cytometric analysis and binding experiments with
      radiolabeled toxins demonstrated that Stx bind to the surface of human mature PMN
      but not to immature PMN from G-CSF-treated donors. The use of the human myeloid
      leukemia cell (HL-60) model for inducible cell differentiation confirmed that the
      toxin binding occurs only after granulocytic differentiation. Stx binding caused
      a delay of the spontaneous apoptosis of PMN, as shown by the delayed appearance
      of apoptotic nuclei and activation of caspase 3 and by the higher number of cells
      negative to the annexin V-binding assay after 48 h. Moreover, flow cytometric
      analysis of mixed Stx-positive and Stx-negative PMN populations showed that the
      toxins were transferred from positive to negative PMN. The delayed, spontaneous
      apoptosis and the passage of the toxic ligand from older PMN to new, mature cells
      entering the circulation from the bone marrow may explain the previously reported
      persistence of Stx in the blood of children with HUS.

PMID- 18625911
TI  - Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)
      induced histamine release is enhanced with SHIP-1 knockdown in cultured human
      mast cell and basophil models.
AB  - Previously, we demonstrated a negative correlation between histamine release to
      histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)
      and protein levels of SHIP-1 in human basophils. The present study was conducted
      to investigate whether suppressing SHIP-1 using small interfering (si)RNA
      technology would alter the releasability of culture-derived mast cells and
      basophils, as determined by HRF/TCTP histamine release. Frozen CD34+ cells were
      obtained from the Fred Hutchinson Cancer Research Center (Seattle, WA, USA).
      Cells were grown in StemPro-34 medium containing cytokines: mast cells with IL-6
      and stem cell factor (100 ng/ml each) for 6-8 weeks and basophils with IL-3 (6.7
      ng/ml) for 2-3 weeks. siRNA transfections were performed during Week 6 for mast
      cells and Week 2 for basophils with siRNA for SHIP-1 or a negative control siRNA.
      Changes in SHIP-1 expression were determined by Western blot. The functional
      knockdown was measured by HRF/TCTP-induced histamine release. siRNA knockdown of
      SHIP-1 in mast cells ranged from 31% to 82%, mean 65 +/- 12%, compared with
      control (n=4). Histamine release to HRF/TCTP was increased only slightly in two
      experiments. SHIP-1 knockdown in basophils ranged from 34% to 69%, mean 51.8 +/-
      7% (n=4). Histamine release to HRF/TCTP in these basophils was dependent on the
      amount of SHIP knockdown. Mast cells and basophils derived from CD34+ precursor
      cells represent suitable models for transfection studies. Reducing SHIP-1 protein
      in cultured mast cells and in cultured basophils increases releasability of the
      cells.

PMID- 18625913
TI  - Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal
      meningitis by activating NADPH oxidase.
AB  - Myeloid cells, including neutrophils and macrophages, play important roles in
      innate immune defense against acute bacterial infections. Myeloid Src family
      kinases (SFKs) p59/61(hck) (Hck), p58(c-fgr) (Fgr), and p53/56(lyn) (Lyn) are
      known to control integrin beta(2) signal transduction and FcgammaR-mediated
      phagocytosis in leukocytes. In this study, we show that leukocyte recruitment
      into the cerebrospinal fluid space and bacterial clearance is hampered in mice
      deficient in all three myeloid SFKs (hck(-/-)fgr(-/-)lyn(-/-)) during
      pneumococcal meningitis. As a result, the hck(-/-)fgr(-/-)lyn(-/-) mice developed
      increased intracranial pressure and a worse clinical outcome (increased
      neurologic deficits and mortality) compared with wild-type mice. Impaired
      bacterial killing was associated with a lack of phagocytosis and superoxide
      production in triple knockout neutrophils. Moreover, in hck(-/-)fgr(-/-)lyn(-/-)
      neutrophils, phosphorylation of p40(phox) was absent in response to pneumococcal
      stimulation, indicating a defect in NAPDH oxidase activation. Mice lacking the
      complement receptor 3 (CR3; CD11b/CD18), which belongs to the beta(2)-integrin
      family, also displayed impaired host defense against pneumococci, along with
      defective neutrophil superoxide production, but cerebrospinal fluid pleocytosis
      was normal. Cerebral expression of cytokines and chemokines was not decreased in
      both mouse strains, indicating that CR3 and myeloid SFKs are dispensable for the
      production of inflammatory mediators. Thus, our study demonstrates the pivotal
      role of myeloid SFKs and CR3 in mounting an effective defense against CNS
      infection with Streptococcus pneumonia by regulating phagocytosis and NADPH
      oxidase-dependent superoxide production. These data support the role of SFKs as
      critical mediators of CR3 signal transduction in host defense.

PMID- 18625915
TI  - What do certification examinations tell us about quality?

PMID- 18625914
TI  - Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by
      inhibiting protein isoprenylation-mediated ERK activation.
AB  - Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is
      up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we
      reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA reductase inhibitor,
      effectively inhibited LPS-stimulated MMP-1 as well as MMP-8 and MMP-9 expression
      by U937 mononuclear cells. Our studies showed that the geranylgeranyl transferase
      inhibitor inhibited LPS-stimulated MMP-1 expression, and addition of isoprenoid
      intermediate geranylgeranyl pyrophosphate (GGPP) reduced the inhibitory effect of
      simvastatin on LPS-stimulated MMP-1 expression. We also demonstrated that
      simvastatin inhibited the activation of Ras and Rac, and the inhibition was
      abolished by addition of GGPP. The above results indicate that protein
      isoprenylation is involved in the regulation of MMP-1 expression by LPS and
      simvastatin. Moreover, we showed that simvastatin inhibited LPS-stimulated
      nuclear AP-1, but not NF-kappaB activity, and the inhibition was reversed by
      addition of GGPP. Simvastatin also inhibited LPS-stimulated ERK but not p38 MAPK
      and JNK. Finally, we showed that the inhibition of LPS-stimulated ERK activation
      by simvastatin was reversed by GGPP. Taken together, this study showed that
      simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by
      targeting protein isoprenylation-mediated ERK activation.

PMID- 18625916
TI  - Shared decision making: have we missed the obvious?

PMID- 18625917
TI  - Statistical models and patient predictors of readmission for heart failure: a
      systematic review.
AB  - BACKGROUND: Readmission after heart failure (HF) hospitalization is an increasing
      focus for physicians and policy makers, but statistical models are needed to
      assess patient risk and to compare hospital performance. We performed a
      systematic review to describe models designed to compare hospital rates of
      readmission or to predict patients' risk of readmission, as well as to identify
      studies evaluating patient characteristics associated with hospital readmission,
      all among patients admitted for HF. METHODS: We identified relevant studies
      published between January 1, 1950, and November 19, 2007, by searching MEDLINE,
      Scopus, PsycINFO, and all 4 Ovid Evidence-Based Medicine Reviews. Eligible
      English-language publications reported on readmission after HF hospitalization
      among adult patients. We excluded experimental studies and publications without
      original data or quantitative outcomes. RESULTS: From 941 potentially relevant
      articles, 117 met inclusion criteria: none contained models to compare
      readmission rates among hospitals, 5 (4.3%) presented models to predict patients'
      risk of readmission, and 112 (95.7%) examined patient characteristics associated
      with readmission. Studies varied in case identification, used multiple types of
      data sources, found few patient characteristics consistently associated with
      readmission, and examined differing outcomes, often either readmission alone or a
      combined outcome of readmission or death, measured across varying periods (from
      14 days to 4 years). Two articles reported model discriminations of patient
      readmission risk, both of which were modest (C statistic, 0.60 for both).
      CONCLUSIONS: Our systematic review identified no model designed to compare
      hospital rates of readmission, while models designed to predict patients'
      readmission risk used heterogeneous approaches and found substantial
      inconsistencies regarding which patient characteristics were predictive.
      Clinically, patient risk stratification is challenging. From a policy
      perspective, a validated risk-standardized statistical model to accurately
      profile hospitals using readmission rates is unavailable in the published English
      language literature to date.

PMID- 18625918
TI  - Relationship, communication, and efficiency in the medical encounter: creating a
      clinical model from a literature review.
AB  - BACKGROUND: While there is consensus about the value of communication skills,
      many physicians complain that there is not enough time to use these skills.
      Little is known about how to combine effective relationship development and
      communication skills with time management to maximize efficiency. Our objective
      was to examine what physician-patient relationship and communication skills
      enhance efficiency. DATA SOURCES: We conducted searches of PubMed, EMBASE, and
      PsychINFO for the date range January 1973 to October 2006. We reviewed the
      reference lists of identified publications and the bibliographies of experts in
      physician-patient communication for additional publications. STUDY SELECTION:
      From our initial group of citations (n = 1146), we included only studies written
      in English that reported original data on the use of communication or
      relationship skills and their effect on time use or visit length. Study inclusion
      was determined by independent review by 2 authors (L.B.M. and D.C.D.). This
      yielded 9 publications for our analysis. DATA EXTRACTION: The 2 reviewers
      independently read and classified the 9 publications and cataloged them by type
      of study, results, and limitations. Differences were resolved by consensus.
      RESULTS: Three domains emerged that may enhance communication efficiency: rapport
      building, up-front agenda setting, and acknowledging social or emotional clues.
      CONCLUSIONS: Building on these findings, we offer a model blending the quality
      enhancing and time management features of selected communication and relationship
      skills. There is a need for additional research about communication skills that
      enhance quality and efficiency.

PMID- 18625919
TI  - Association between maintenance of certification examination scores and quality
      of care for medicare beneficiaries.
AB  - BACKGROUND: The relationship between physicians' cognitive skill and the delivery
      of evidence-based processes of care is not well characterized.Therefore, we set
      out to determine associations between general internists' performance on the
      American Board of Internal Medicine maintenance of certification examination and
      the receipt of important processes of care by Medicare patients. METHODS:
      Physicians were grouped into quartiles based on their performance on the American
      Board of Internal Medicine examination. Hierarchical generalized linear models
      examined associations between examination scores and the receipt of processes of
      care by Medicare patients. The main outcome measures were the associations
      between diabetes care, using a composite measure of hemoglobin A(1c), and lipid
      testing and retinal screening, mammography, and lipid testing in patients with
      cardiovascular disease and the physician's performance on the American Board of
      Internal Medicine examination, adjusted for the number of Medicare patients with
      diabetes and cardiovascular disease in a physician's practice panel; frequency of
      visits; patient comorbidity, age, and ethnicity; and physician training history
      and type of practice. RESULTS: Physicians scoring in the top quartile were more
      likely to perform processes of care for diabetes (composite measure odds ratio
      [OR], 1.17; 95% confidence interval [CI], 1.07-1.27) and mammography screening
      (OR, 1.14; 95% CI, 1.08-1.21) than physicians in the lowest physician quartile,
      even after adjustment for multiple factors. There was no significant difference
      among the groups in lipid testing of patients with cardiovascular disease (OR,
      1.00; 95% CI, 0.91-1.10). CONCLUSION: Our findings suggest that physician
      cognitive skills, as measured by a maintenance of certification examination, are
      associated with higher rates of processes of care for Medicare patients.

PMID- 18625920
TI  - Physicians' shared decision-making behaviors in depression care.
AB  - BACKGROUND: Although shared decision making (SDM) has been reported to facilitate
      quality care, few studies have explored the extent to which SDM is implemented in
      primary care and factors that influence its application. This study assesses the
      extent to which physicians enact SDM behaviors and describes factors associated
      with physicians' SDM behaviors within the context of depression care. METHODS: In
      a secondary analysis of data from a randomized experiment, we coded 287
      audiorecorded interactions between physicians and standardized patients (SPs)
      using the Observing Patient Involvement (OPTION) system to assess physician SDM
      behaviors. We performed a series of generalized linear mixed model analyses to
      examine physician and patient characteristics associated with SDM behavior.
      RESULTS: The mean (SD) OPTION score was 11.4 (3.3) of 48 possible points. Older
      physicians (partial correlation coefficient = -0.29; beta = -0.09; P < .01) and
      physicians who practiced in a health maintenance organization setting (beta = 
      1.60; P < .01) performed fewer SDM behaviors. Longer visit duration was
      associated with more SDM behaviors (partial correlation coefficient = 0.31; beta
      = 0.08; P < .01). In addition, physicians enacted more SDM behaviors with SPs who
      made general (beta = 2.46; P < .01) and brand-specific (beta = 2.21; P < .01)
      medication requests compared with those who made no request. CONCLUSIONS: In the
      context of new visits for depressive symptoms, primary care physicians performed
      few SDM behaviors. However, physician SDM behaviors are influenced by practice
      setting and patient-initiated requests for medication. Additional research is
      needed to identify interventions that encourage SDM when indicated.

PMID- 18625921
TI  - Hidden in plain sight: medical visit companions as a resource for vulnerable
      older adults.
AB  - BACKGROUND: Sicker patients are less satisfied with the quality of health care
      they receive than their healthier counterparts. METHODS: A sample of 12,018
      community-dwelling Medicare beneficiaries 65 years or older from the 2004
      Medicare Current Beneficiary Survey was studied. Multivariate regression was used
      to describe whether beneficiaries' self-reported satisfaction with their usual
      care physician was related to the presence or functions assumed by visit
      companions. RESULTS: Overall, 38.6% of beneficiaries reported being typically
      accompanied to routine medical visits. Accompanied beneficiaries were older, less
      educated, and in worse health than their unaccompanied counterparts. More than
      60% of companions facilitated visit communication by recording physician
      instructions (44.1%), providing information regarding patients' medical
      conditions or needs (41.6%), asking questions (41.1%), or explaining physicians'
      instructions (29.7%). After controlling for sociodemographic and health
      differences, accompanied beneficiaries were more highly satisfied with their
      physician's technical skills (odds ratio [OR], 1.15; 95% confidence interval
      [CI], 1.02-1.30), information giving (OR, 1.19; 95% CI, 1.05-1.35), and
      interpersonal skills (OR, 1.18; 95% CI, 1.03-1.35) than unaccompanied
      beneficiaries. Accompanied beneficiaries whose visit companions were more
      actively engaged in communication rated physician information giving (OR, 1.42;
      95% CI, 1.14-1.77) and interpersonal skills (OR, 1.29; 95% CI, 1.05-1.59) more
      favorably. This relationship was strongest among beneficiaries with the worst
      self-rated health. CONCLUSIONS: Visit companions are commonly present in older
      adults' routine medical encounters, actively engaged in care processes, and
      influential to patients' satisfaction with physician care. More systematic
      recognition and integration of visit companions in health care processes may
      benefit quality of care for a particularly vulnerable patient population.

PMID- 18625922
TI  - Development and validation of a model for predicting emergency admissions over
      the next year (PEONY): a UK historical cohort study.
AB  - BACKGROUND: Current international health policy has emphasized the importance of
      managing long-term conditions in the community with the aim of preventing
      emergency hospitalizations. Previous algorithms and rules have been developed but
      are limited to those older than 65 years and generally only for readmission. Our
      aim was to develop an algorithm to predict emergency hospital admissions in the
      whole population of those 40 years or older. METHODS: The design was a historical
      cohort observational study from 1996 to 2004 with at least 1 year of follow-up
      and split-half validation, set in the population of Tayside, Scotland (n = 410
      000). Participants were 40 years or older with a 3-year history of prescribed
      drugs and hospital admissions. The main outcome measure was first emergency
      hospital admission in the following year, analyzed using logistic regression.
      RESULTS: A total of 186 523 subjects 40 years or older were identified at
      baseline. A derivation data set (n = 90 522) yielded 6793 participants (7.5%) who
      experienced an emergency hospital admission in the following year. Strong
      predictors of admissions were age; being male; high social deprivation;
      previously prescribed analgesics, antibacterials, nitrates, and diuretics; the
      number of respiratory medications; and the number of previous admissions and
      previous total bed-days. Discriminatory power was good (c statistic, 0.80) and
      split-half validation gave good calibration, especially for the highest decile of
      risk. CONCLUSIONS: A population-derived algorithm provided the first easy-to-use
      algorithm, to our knowledge, to predict future emergency admissions in all
      individuals 40 years or older. The model can be implemented at individual patient
      level as well as family practice level to target case management.

PMID- 18625924
TI  - Joint replacement surgery in elderly patients with severe osteoarthritis of the
      hip or knee: decision making, postoperative recovery, and clinical outcomes.
AB  - BACKGROUND: Osteoarthritis (OA) of the hip and knee is a common cause of pain and
      disability in elderly patients. Joint replacement surgery can alleviate pain and
      restore function but is associated with risks and discomfort. METHODS: We
      conducted a prospective cohort study to examine decision making and clinical
      outcomes for elderly patients (age >or=65 years) with severe OA of the hip or
      knee with symptoms inadequately controlled with conservative treatments.
      Osteoarthritis symptoms and functional status were assessed at baseline and at 12
      months. Postoperative symptoms and function were assessed 6 weeks, 6 months, and
      12 months after surgery. RESULTS: For the 174 patients studied (mean age, 75
      years; 76% were female, 17% were nonwhite, 69% had knee OA, and 31% had hip OA),
      the mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      score was 56 on a 100-point scale. During a 12-month follow-up, 29% had joint
      replacement surgery. Of patients who had surgery, no patients died, 17% had
      postoperative complications, and 38% had postoperative pain lasting more than 4
      weeks. The median time to recovery of independence in walking was 12 days and to
      ability to perform household chores was 49 days, with similar times for patients
      65 to 74 years old and those 75 years or older. At 12 months, WOMAC scores
      improved by 24 points in the patients who had surgery and 0.5 point in the
      patients who did not have surgery (P < .001); improvements were 19 and 0.3 points
      in patients 75 or older (P < .001). Among patients who did not have surgery, 45%
      reported that surgery was not offered as a potential treatment option.
      CONCLUSIONS: Elderly patients who had hip or knee replacements for severe OA took
      several weeks to recover but experienced excellent long-term outcomes. Physicians
      often do not discuss joint replacement surgery with elderly patients who might
      benefit.

PMID- 18625923
TI  - Inducible ischemia and the risk of recurrent cardiovascular events in outpatients
      with stable coronary heart disease: the heart and soul study.
AB  - BACKGROUND: Current guidelines do not recommend routine cardiac stress testing in
      patients with stable coronary heart disease (CHD) unless they report symptoms of
      angina. Our objective was to compare the prognosis of self-reported angina
      symptoms, inducible ischemia, or both in patients with stable CHD. METHODS: We
      measured self-reported angina by questionnaire and inducible ischemia using
      treadmill stress echocardiography in 937 outpatients with stable CHD. We used Cox
      proportional hazard models, adjusted for traditional cardiovascular risk factors,
      to evaluate the independent association of angina and inducible ischemia with CHD
      events (myocardial infarction or CHD death) during a mean of 3.9 years of follow
      up. RESULTS: Of the study participants, 129 (14%) had angina alone, 188 (20%) had
      inducible ischemia alone, and 40 (4%) had both angina and ischemia. Recurrent CHD
      events occurred in 7% of participants without angina or inducible ischemia, 10%
      of those with angina alone, 21% of those with inducible ischemia alone, and 23%
      of those with both angina and inducible ischemia (P < .001). The presence of
      angina alone was not associated with recurrent CHD events (adjusted hazard ratio,
      1.4; 95% confidence interval, 0.7-2.9) (P = .31). However, the presence of
      inducible ischemia without self-reported angina strongly predicted recurrent CHD
      events (adjusted hazard ratio, 2.2; 95% CI, 1.4-3.5) (P = .005). CONCLUSIONS: We
      found that 24% of patients with stable CHD had inducible ischemia, and more than
      80% of these patients did not report angina. The presence of inducible ischemia
      without self-reported angina is associated with a greater than 2-fold increased
      rate of recurrent CHD events.

PMID- 18625925
TI  - Prevalence of low sexual desire and hypoactive sexual desire disorder in a
      nationally representative sample of US women.
AB  - BACKGROUND: We sought to estimate the prevalence of low sexual desire and
      hypoactive sexual desire disorder (HSDD) in US women, focusing on their
      menopausal status. METHODS: We performed a cross-sectional study. From a
      probability sample of households, 2207 US women aged 30 to 70 years and in stable
      relationships (>or=3 months) were interviewed by telephone. The analysis focused
      on 755 premenopausal women and 552 naturally and 637 surgically menopausal women.
      Low sexual desire was defined using the Profile of Female Sexual Function desire
      domain, and HSDD was defined using the Profile of Female Sexual Function and the
      Personal Distress Scale. RESULTS: Prevalence of low sexual desire ranged from
      26.7% among premenopausal women to 52.4% among naturally menopausal women. The
      prevalence of HSDD was highest among surgically menopausal women (12.5%).
      Compared with premenopausal women and adjusting for age, race/ethnicity,
      educational level, and smoking status, the prevalence ratios for HSDD were 2.3
      (95% confidence interval, 1.2-4.5) for surgically menopausal women and 1.2 (0.5
      2.8) for naturally menopausal women; the prevalence ratios for low sexual desire
      were 1.3 (0.9-1.9) and 1.5 (1.0-2.2) for surgically and naturally menopausal
      women, respectively. CONCLUSIONS: Prevalence of low sexual desire is elevated
      among surgically and naturally menopausal women vs premenopausal women. Distress
      about low desire (HSDD) appears to be more than twice as prevalent among
      surgically menopausal women vs premenopausal women, although the estimate is
      fairly imprecise.

PMID- 18625926
TI  - Altered blood pressure progression in the community and its relation to clinical
      events.
AB  - BACKGROUND: Long-term blood pressure (BP) progression and its importance as a
      predictor of clinical outcome have not been well characterized across different
      periods. METHODS: We evaluated period trends for 3 BP variables (long-term slope
      and mean BP during a baseline period of 16 years, and last baseline value) in an
      earlier period (1953-1971; n = 1644, mean participant age, 61 years) and in a
      later period (1971-1990; n = 1040, mean participant age, 58 years) in
      participants in the Framingham Heart Study who initially did not have
      hypertension. In addition, we explored the relation of BP to cardiovascular
      disease incidence and all-cause mortality in the 2 periods, each with up to 16
      years of follow-up. RESULTS: Long-term slope, mean, and last baseline BP
      measurements were significantly lower in the later period (P < .001). Rates of
      hypertension control (BP <140/90 mm Hg) were higher in the later vs the earlier
      period (32% vs 23%; P < .001). Multivariate hazard ratios for the relation of BP
      to outcomes were generally lower in the later period; this was statistically
      significant for the relation of last baseline BP to all-cause mortality (hazard
      ratio for 1-SD increase in systolic BP, 1.02 vs 1.25, P = .03; hazard ratio for
      diastolic BP, 1.00 vs 1.23, P = .04). CONCLUSIONS: We found evidence that BP
      levels in the community have changed over time, coinciding with improved rates of
      hypertension control and attenuation of BP-mortality relations. These findings
      are consistent with the hypothesis that hypertension treatment in the community
      has altered the natural history of BP progression and its relation to clinical
      outcome.

PMID- 18625927
TI  - Same-sex attraction disclosure to health care providers among New York City men
      who have sex with men: implications for HIV testing approaches.
AB  - BACKGROUND: While the Centers for Disease Control and Prevention recommends at
      least annual human immunodeficiency virus (HIV) screening for men who have sex
      with men (MSM), a large number of HIV infections among this population go
      unrecognized. We examined the association between disclosing to their medical
      providers (eg, physicians, nurses, physician assistants) same-sex attraction and
      self-reported HIV testing among MSM in New York City, New York. METHODS: All men
      recruited from the New York City National HIV Behavioral Surveillance (NHBS)
      project who reported at least 1 male sex partner in the past year and self
      reported as HIV seronegative were included in the analysis. The primary outcome
      of interest was a participant having told his health care provider that he is
      attracted to or has sex with other men. Sociodemographic and behavioral factors
      were examined in relation to disclosure of same-sex attraction. RESULTS: Among
      the 452 MSM respondents, 175 (39%) did not disclose to their health care
      providers. Black and Hispanic MSM (adjusted odds ratios, 0.28 [95% confidence
      interval, 0.14-0.53] and 0.46 [95% confidence interval, 0.24-0.85], respectively)
      were less likely than white MSM to have disclosed to their health care providers.
      No MSM who identified themselves as bisexual had disclosed to their health care
      providers. Those who had ever been tested for HIV were more likely to have
      disclosed to their health care providers (adjusted odds ratio, 2.10; 95%
      confidence interval, 1.01-4.38). CONCLUSIONS: These data suggest that risk-based
      HIV testing, which is contingent on health care providers being aware of their
      patients' risks, could miss these high-risk persons.

PMID- 18625928
TI  - Predicting death in elderly patients with community-acquired pneumonia: a
      prospective validation study reevaluating the CRB-65 severity assessment tool.

PMID- 18625929
TI  - Mortality in humans with pneumonia and sepsis is related to an uncompensated anti
      inflammatory response to infection.

PMID- 18625930
TI  - Occupational exposure and rapid HIV test.

PMID- 18625931
TI  - Opportunity realized? Medical consultation for patients undergoing major surgery.

PMID- 18625932
TI  - Dehydroepiandrosterone sulfate has not been substantiated as an anabolic hormone.

PMID- 18625933
TI  - Sutured protective occluder for severe amblyopia.
AB  - OBJECTIVE: To investigate the feasibility, acceptability, efficacy, and cost of a
      newly developed translucent shield that can be fixed by sutures to the orbital
      rim for a month of amblyopia therapy. METHODS: In an institutional review board
      approved protocol for patients with amblyopia who do not adhere to the use of
      conventional patching, shield occluders were fashioned from heat-moldable sturdy
      black or translucent (20/4000) plastic with holes drilled for attachment. Under
      brief general anesthesia, patients aged 5 to 10 years had a thorough examination
      before the shield occluder was sewn to the brow and cheek of the nonamblyopic eye
      with 3-0 monofilament polypropylene sutures. RESULTS: Ten children completed this
      protocol from December 1999 through January 2002. All tolerated the occluder for
      12 to 36 days. The resultant skin scars were acceptable to parents, patients, and
      investigators. The amblyopic eyes improved from a mean (SD) of 0.77 (0.30) logMAR
      (Snellen equivalent, 20/119) to 0.45 (0.29) logMAR (Snellen equivalent, 20/57), a
      change of 0.32 (0.16) logMAR lines. There was no damage to the sound (occluded)
      eye. CONCLUSION: Sew-on occluder shields are an alternative when adherence to the
      use of other types of patching (often referred to as compliance with patching) is
      not satisfactory.

PMID- 18625934
TI  - Head position-dependent changes in ocular torsion and vertical misalignment in
      skew deviation.
AB  - OBJECTIVES: To investigate whether ocular torsion and vertical misalignment
      differ in the upright vs supine position in skew deviation and to compare these
      findings with those in trochlear nerve palsy. METHODS: Ten patients with skew
      deviation, 14 patients with unilateral peripheral trochlear nerve palsy, and 12
      healthy subjects were prospectively recruited. With subjects first in the upright
      position and then in the supine position, ocular torsion was measured by double
      Maddox rods and vertical misalignment was measured by the prism and alternate
      cover test. RESULTS: In patients with skew deviation, the abnormal torsion and
      vertical misalignment in the upright position decreased substantially with change
      to the supine position, whereas in patients with trochlear nerve palsy, it
      changed little between positions. Torsion was decreased by 83% in patients with
      skew deviation, 2% in patients with trochlear nerve palsy, and 6% in healthy
      subjects (P < .001). Similarly, vertical misalignment was decreased by 74% in
      patients with skew deviation and increased by 5% in patients with trochlear nerve
      palsy and 6% in healthy subjects (P < .001). CONCLUSIONS: Our findings provide
      the basis for additional clinical tests to support the classic 3-step test:
      ocular torsion and vertical misalignment that decrease from the upright position
      to the supine position indicate skew deviation, whereas torsion and vertical
      misalignment that do not change significantly between positions indicate
      trochlear nerve palsy.

PMID- 18625935
TI  - Visual insignificance of the foveal pit: reassessment of foveal hypoplasia as
      fovea plana.
AB  - OBJECTIVES: To elucidate the visual significance of the foveal pit by measuring
      foveal architecture and function and to reassess use of the term foveal
      hypoplasia (as visual acuity can vary among patients who lack a pit). METHODS: We
      describe 4 patients who lack a foveal pit. Visual acuities ranged from 20/20 to
      20/50. Stratus and Cirrus (Carl Zeiss Meditec, Dublin, California) optical
      coherence tomographs (OCTs) and multifocal electroretinograms were obtained. High
      resolution retinal imaging on 2 of the participants was obtained by using a high
      resolution Fourier-domain OCT and an adaptive optics flood-illuminated fundus
      camera. RESULTS: No participants had a visible foveal pit with conventional OCT.
      Central widening of the outer nuclear layer and lengthening of cone outer
      segments were seen with high-resolution Fourier-domain OCT. Adaptive optics
      imaging showed normal cone diameters in the central 1 degrees to 2 degrees.
      Central multifocal electroretinogram responses were normal. CONCLUSIONS: We show
      that a foveal pit is not required for foveal cone specialization, anatomically or
      functionally. This helps to explain the potential for good acuity in the absence
      of a pit and raises questions about the visual role of the foveal pit. Because
      the term foveal hypoplasia commonly carries a negative functional implication, it
      may be more proper to call the anatomic lack of a pit fovea plana.

PMID- 18625936
TI  - Aqueous humor dynamics in exfoliation syndrome.
AB  - OBJECTIVE: To examine how aqueous humor dynamics are affected by exfoliation
      syndrome (XFS) with or without elevated intraocular pressure (IOP). METHODS:
      Eighty participants were divided into 4 groups: (1) those with XFS and ocular
      normotension (n = 25), (2) controls with ocular normotension without XFS, age
      matched to group 1 (n = 25), (3) those with XFS and ocular hypertension (n = 15),
      and (4) controls with ocular hypertension without XFS, age-matched to group 3 (n
      = 15). Following washout of glaucoma medications, assessments were made of IOP,
      episcleral venous pressure, aqueous flow, outflow facility, and uveoscleral
      outflow. Differences were analyzed by group mean comparisons and linear
      regression analyses. RESULTS: Uveoscleral outflow was significantly decreased in
      individuals with XFS compared with age-matched controls and was independent of
      IOP. Patients with ocular hypertension (with or without XFS) exhibited decreased
      outflow facility compared with those with ocular normotension (with or without
      XFS). Aqueous flow was not affected by the level of IOP or the presence of XFS.
      CONCLUSIONS: Exfoliation syndrome in normotensive and hypertensive eyes is
      associated with a decrease in uveoscleral outflow, whereas in hypertensive but
      not normotensive eyes, it is associated with reduced outflow facility.

PMID- 18625937
TI  - Early predictors of traumatic glaucoma after closed globe injury: trabecular
      pigmentation, widened angle recess, and higher baseline intraocular pressure.
AB  - OBJECTIVE: To prospectively analyze the clinical and ultrasonographic
      biomicroscopy (UBM) features in eyes with closed globe injury, at the initial
      examination, that would predict the occurrence of chronic traumatic glaucoma
      during a 6-month follow-up. METHODS: Forty consecutive eyes with closed globe
      injury and a chronically elevated intraocular pressure (IOP) of at least 21 mm Hg
      for a minimum of 3 months were diagnosed as having traumatic glaucoma and
      compared with 52 eyes with closed globe injury and no evidence of glaucoma.
      RESULTS: The median grade of trabecular pigmentation on gonioscopy in eyes with
      traumatic glaucoma was 3 compared with 2 in eyes without glaucoma (P = .001). On
      UBM findings, 18 eyes with closed globe injury without glaucoma showed evidence
      of cyclodialysis, compared with 7 eyes with glaucoma (P = .001). The relative
      risk of developing traumatic glaucoma was also significantly higher with hyphema,
      elevated baseline IOP, angle recession of more than 180 degrees, lens
      displacement, and wider angles on UBM. CONCLUSIONS: Clinically, the presence of
      increased pigmentation at the angle, elevated baseline IOP, hyphema, lens
      displacement, and angle recession of more than 180 degrees were significantly
      associated with the occurrence of chronic glaucoma after closed globe injury. On
      UBM findings, a wider angle and the absence of cyclodialysis were significant
      predictors for the subsequent development of traumatic glaucoma.

PMID- 18625938
TI  - Comparison of predictions made by the intraocular lens master and ultrasound
      biometry.
AB  - OBJECTIVE: To ascertain whether a new instrument that uses partial coherence
      interferometry technology (Intraocular Lens Master [IOLm]) or ultrasound biometry
      provides a more accurate prediction of refractive outcomes in cataract surgery.
      METHODS: This was a retrospective medical record review of 421 eyes of 304
      patients who underwent cataract surgery with the IOLm and ultrasound biometry
      from January 3, 2002, to December 2, 2005. The mean difference between the
      prediction with each technology and the final spherical equivalent was compared.
      Circumstances in which both technologies failed to make accurate predictions were
      investigated. RESULTS: The mean (SD) of the difference between predicted
      refraction and final spherical equivalent was -0.43 (0.84) diopters (D) for the
      IOLm and -0.60 (0.87) D for ultrasound biometry, indicating that on average the
      IOLm was a closer predictor than ultrasound biometry of the final spherical
      equivalent (P < .001). The IOLm had a 5% higher likelihood of predicting a
      spherical equivalent within 0.25 D than ultrasound biometry (P = .06), an 8%
      higher likelihood of predicting a spherical equivalent within 0.50 D (P < .001),
      and an 8% higher likelihood of predicting a spherical equivalent within 1.00 D (P
      < .001). CONCLUSIONS: To our knowledge, this is the most eyes examined for
      cataract surgery in a prospective fashion with both the IOLm and ultrasound
      biometry. The IOLm is a better predictor of postoperative refraction than
      ultrasound biometry, particularly within close ranges.

PMID- 18625940
TI  - Bevacizumab treatment for subfoveal choroidal neovascularization from causes
      other than age-related macular degeneration.
AB  - OBJECTIVE: To report the results of intravitreous bevacizumab (Avastin) treatment
      for choroidal neovascularization (CNV) from causes other than age-related macular
      degeneration (AMD). METHODS: We performed a retrospective analysis of eyes that
      received intravitreous bevacizumab, 1.25 mg, for subfoveal non-AMD CNV at a
      referral-based retinal practice. Repeated treatment with intravitreous
      bevacizumab occurred if there were signs of persistent or recurrent exudation.
      The main outcome measure was visual acuity (VA). RESULTS: The study included 39
      eyes of 36 patients with subfoveal CNV secondary to multifocal choroiditis (n =
      12), angioid streaks (n = 11), myopic degeneration (n = 10), idiopathic disease
      (n = 4), or other disease (n = 2). The median baseline VA was 20/60 (logMAR,
      0.48). The mean follow-up was 58.8 weeks, and the mean number of injections per
      eye was 3.4. After 3-month follow-up, the median VA was 20/30 (logMAR, 0.18) (P =
      .004 vs baseline). At last follow-up, the median VA was 20/40 (logMAR, 0.30).
      This remained an improvement compared with baseline (P < .02) but was worse than
      3-month follow-up (P < .03). There was no correlation between underlying
      diagnosis and VA change during follow-up. CONCLUSION: Subfoveal CNV secondary to
      non-AMD causes treated with intravitreous bevacizumab responded favorably and
      similarly, despite varying underlying etiologies.

PMID- 18625939
TI  - Rapid, noninvasive detection of diabetes-induced retinal metabolic stress.
AB  - OBJECTIVE: To test whether subjects with diabetes mellitus (DM) have enhanced
      retinal flavoprotein autofluorescence compared with age-matched control subjects
      using a rapid, noninvasive clinical imaging method. METHODS: Twenty-one subjects
      with DM and 21 healthy age-matched control volunteers were subjected to retinal
      imaging using 1-ms flashes of 467-nm light. Flavoprotein autofluorescence for
      each flash at 535 nm was recorded using an electron-multiplying charged-coupled
      device camera with a 512x512-pixel chip. The average intensity and the average
      curve width of retinal flavoprotein autofluorescence were determined by analyzing
      histograms of pixel intensities plotted for each eye. RESULTS: When stratified by
      age, the mean average intensity and average curve width levels in subjects with
      DM were significantly greater than those in controls across all 3 consecutive
      decades of life studied (P < or = .004 and P < or = .006, respectively). An
      overall comparison of the mean average intensity and average curve width levels
      in all subjects with DM vs all controls, with adjustment for age, was consistent
      with the results found in each age category (P =.001 and P < .001, respectively).
      Subjects having DM with retinopathy in at least 1 eye had significantly greater
      average intensity and average curve width than subjects having DM without
      retinopathy in either eye (P =.002 and P =.005, respectively). CONCLUSIONS:
      Flavoprotein autofluorescence measurements may be clinically useful to rapidly
      and noninvasively identify diabetic metabolic tissue stress and disease severity.
      Development of flavoprotein autofluorescence technology is likely to result in a
      tool that will improve DM screening and disease management.

PMID- 18625941
TI  - Comparing pegaptanib and triamcinolone efficacy in the rat choroidal
      neovascularization model.
AB  - OBJECTIVE: To evaluate the prophylactic effect of intravitreal pegaptanib sodium
      on choroidal neovascularization membrane (CNVM) development and compare its
      performance with that of triamcinolone acetonide. METHODS: In drug-treated and
      control groups, CNVMs were induced by laser trauma. Immediately after undergoing
      the laser procedure, animals received intravitreal injections of pegaptanib
      sodium, 8 or 17 mug; triamcinolone acetonide, 200 mug; or a vehicle solution.
      After 21 days, fluorescein angiography was performed. The CNVM mean diameters and
      radial thicknesses were measured histologically. RESULTS: Mean CNVM diameters
      were 10% to 13% smaller in pegaptanib-treated eyes and 43% smaller in
      triamcinolone-treated eyes compared with laser-only control eyes. Late-stage
      fluorescein angiography leakage scores, on a scale of 0 to 3, suggested a
      statistical difference between triamcinolone- (0.6) and pegaptanib(8 microg)
      treated (1.5) groups compared with the laser-only control group (2.0). The CNVM
      mean thicknesses were greater in the pegaptanib(8 microg)- (79 microm) and
      pegaptanib(17 microg)-treated (71 microm) groups and significantly smaller in the
      triamcinolone-treated group (26 microm) compared with the laser-only control
      group (67 microm). CONCLUSION: In this animal model of choroidal
      neovascularization, intravitreal pegaptanib exhibited marginal or no effect on
      CNVM development; whereas intravitreal triamcinolone evoked robust inhibition of
      CNVMs. Clinical Relevance Pegaptanib treatment may be insufficient to prevent
      CNVM formation.

PMID- 18625942
TI  - Inhibitory effect of bevacizumab on the angiogenesis and growth of
      retinoblastoma.
AB  - OBJECTIVE: To evaluate the potential effect of bevacizumab, a monoclonal antibody
      against vascular endothelial growth factor (VEGF), on the angiogenesis and tumor
      growth of retinoblastoma in vitro and in vivo. METHODS: The antiangiogenic
      effects of bevacizumab were evaluated in a coculture of a Y-79 human
      retinoblastoma cell line and a human umbilical vein endothelial cell line by
      means of a cell proliferation assay kit and a VEGF enzyme-linked immunosorbent
      assay. The Y-79 xenotransplanted nude mice were treated with bevacizumab
      intraperitoneally twice weekly for 4 weeks, during which each tumor was measured
      once a week. The mice were then euthanized, and the weight of each tumor and its
      microvessel density were determined via CD34 immunohistochemical staining.
      RESULTS: The mean (standard error of the mean) increased human umbilical vein
      endothelial cell proliferation, when cocultured with Y-79 (156% [1%]), was
      suppressed 58% (5%) by the blockage of VEGF induced by bevacizumab. By causing a
      2-fold reduction in microvessel density in the Y-79 xenograft model, bevacizumab
      induced a 75% reduction in the growth of the retinoblastomas without producing
      significant systemic toxicity. Conclusions and Clinical Relevance Treatment with
      bevacizumab suppressed the angiogenesis and growth of retinoblastoma in vitro and
      in vivo. Bevacizumab is likely to be of benefit in the treatment of
      retinoblastoma.

PMID- 18625943
TI  - Intraocular pressure response to topical beta-blockers associated with an ADRB2
      single-nucleotide polymorphism.
AB  - OBJECTIVES: To determine whether candidate pharmacodynamic (beta-adrenergic
      receptor) and pharmacokinetic (cytochrome P450 2D6) gene polymorphisms are
      associated with the intraocular pressure (IOP) response to topical beta-blockers.
      METHODS: Medical records of 18,773 adults in the Personalized Medicine Research
      Project were searched to extract all IOP measurements for subjects who had been
      prescribed a topical beta-blocker. Five single-nucleotide polymorphisms in the
      beta(1)-, beta(2)-, and beta(3)-adrenergic receptor genes and 6 polymorphisms in
      the CYP2D6 gene were genotyped. RESULTS: A total of 58.1% of the subjects were
      female; the mean age was 63.8 years. Topical beta-blockers were prescribed for
      343 eyes of 215 subjects. An IOP reduction of 20% or more in 1 or both eyes was
      observed in 61.0% of subjects. Men were significantly more likely than women to
      have an IOP decrease of 20% or more (69.3% vs 54.9%, respectively; chi(2) = 4.48;
      P = .04). After adjusting for sex, family history of glaucoma, and use of
      systemic beta-blockers, subjects with the CC genotype at coding single-nucleotide
      polymorphism rs1042714 in the ADRB2 gene were significantly more likely to
      experience an IOP decrease of 20% or more (odds ratio, 2.00; 95% confidence
      interval, 1.00-4.02). CONCLUSION: We found that a coding single-nucleotide
      polymorphism in ADRB2 is associated with an increased likelihood of a clinically
      meaningful IOP response to topical beta-blockers. Clinical Relevance Because
      topical beta-blockers are the least expensive class of agents used to lower IOP,
      genotype-based drug prescribing could save health care dollars.

PMID- 18625944
TI  - Bilateral infusion pump implants as therapy for refractory corneal ulcers in a
      patient with CREST syndrome: an interdisciplinary approach.
AB  - Internal infusion pumps are implantable and programmable systems that have been
      widely used for years in the management of chronic pain. During the past few
      years, these devices have had an increasingly prominent role given the
      possibility of insulin infusions in patients with diabetes mellitus because they
      provide patients with higher autonomy in the management of their disease, despite
      the fact that they are expensive systems and require surgery for implantation.
      These features make internal infusion pumps a suitable therapeutic option for
      those patients who need to use artificial tears continuously because of severe
      dry eyes. We report a case of severe eye pain due to xerophthalmia in a patient
      with CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility,
      sclerodactyly, and telangiectasia) syndrome who was treated with an implanted
      pump reservoir.

PMID- 18625945
TI  - Knowledge of diabetic eye disease and vision care guidelines among Hispanic
      individuals in Baltimore with and without diabetes.
AB  - OBJECTIVE: To determine gaps in knowledge and barriers to care for diabetic eye
      disease in Hispanic individuals in Baltimore, Maryland. METHODS: Interviews with
      a random sample of self-reported Hispanic individuals (n = 349), and a
      convenience sample of Hispanic individuals with diabetes (n = 204). Four groups
      were constructed: without diabetes, with and without a family history of
      diabetes, newly diagnosed with diabetes, and diagnosed with diabetes more than 1
      year before the study. RESULTS: Less than 10% of participants preferred reading
      in English; 50% reported having providers who do not speak Spanish as a barrier
      to care. Knowledge of eye disease as a consequence of diabetes was reported by
      18% of nondiabetic participants with no family history, 29% of nondiabetic
      participants with a family history, 36% of newly diagnosed diabetic patients, and
      52% of participants diagnosed with diabetes more than 1 year before the study.
      Only 16%, 28%, 13%, and 34%, respectively, knew that strict control could prevent
      eye problems, and 33%, 51%, 31%, and 48%, respectively, knew that dilated eye
      examinations were important. A total of 30% of diabetic participants had had an
      eye examination in the previous year. CONCLUSIONS: Knowledge of the ocular
      complications of diabetes is low. The frequency of eye examinations among
      Hispanic individuals with diabetes is less than the national average for Hispanic
      individuals. Culturally appropriate health education and innovations to reduce
      barriers to eye care are needed.

PMID- 18625947
TI  - Corneal thickness and intraocular pressure in a nonglaucomatous Burmese
      population: the Meiktila Eye Study.
AB  - OBJECTIVE: To determine correlates of central corneal thickness (CCT) and its
      relationship to intraocular pressure (IOP) in a Burmese population. METHODS: We
      performed a population-based survey of inhabitants 40 years or older in Myanmar;
      of 2076 participants, data from 1909 nonglaucomatous subjects who underwent
      ultrasound pachymetry and Goldmann applanation tonometry were analyzed. Linear
      mixed effects models adjusting for nonindependence of right and left eye data
      were constructed. RESULTS: Mean (SD) CCT was 521.9 (33.3) microm, and the mean
      (SD) IOP was 14.5 (3.4) mm Hg. Intraocular pressure and spherical equivalent were
      significant predictors of CCT (P < .001 and P = .01, respectively). Age, sex,
      body mass index, and corneal curvature were not significant predictors. Central
      corneal thickness was the only significant predictor of IOP (ie, an increase of
      100 microm in CCT predicted an increase of 1.3 mm Hg in IOP). The Spearman
      correlation between CCT and IOP for the right and left eyes was highly
      significant (P < .001), but the Spearman rank correlation values (R(2) = 0.016
      and R(2) = 0.017, respectively) were weak. CONCLUSIONS: The CCT in this Burmese
      population was significantly associated with IOP and spherical equivalent. The
      weak association between CCT and IOP is consistent with that of other population
      based studies. Other corneal factors are likely to influence Goldmann applanation
      tonometry.

PMID- 18625946
TI  - Reported visual impairment and risk of suicide: the 1986-1996 national health
      interview surveys.
AB  - OBJECTIVE: To examine the relationship between reported visual impairment and
      suicide mortality. METHODS: From 1986 through 1996, annual cross-sectional
      multistage area probability surveys of the US civilian noninstitutionalized
      population living at addressed dwellings were conducted by the National Center
      for Health Statistics. We performed mortality linkage through 2002 with the
      National Death Index of 137,479 adults 18 years and older. The relationships
      between reported visual impairment and suicide were examined using structural
      equation modeling. RESULTS: The mean duration of follow-up was 11.0 years, and
      200 suicide deaths were identified. After controlling for survey design, age,
      sex, race, marital status, number of nonocular health conditions, and self-rated
      health, the direct effect of visual impairment on death from suicide was elevated
      but not significant (hazard ratio, 1.50; 95% confidence interval, 0.90-2.49). The
      approximate indirect effect of visual impairment on death from suicide via poorer
      self-rated health (1.05; 1.02-1.08) or number of nonocular health conditions
      (1.12; 1.01-1.24) was significant. The total effect of visual impairment on death
      from suicide was elevated but not significant (1.64; 0.99-2.72). CONCLUSIONS:
      Visual impairment may be associated with an increased risk of suicide through its
      effect on poor health. This suggests that improved treatment of visual impairment
      and factors causing poor health may potentially reduce suicide risk.

PMID- 18625948
TI  - Identification of patients with diabetic macular edema from claims data: a
      validation study.
AB  - OBJECTIVE: To assess the validity of an algorithm for identifying patients with
      diabetic macular edema (DME) using International Classification of Diseases,
      Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in
      administrative billing data from a convenience sample of physician offices.
      METHODS: A convenience sample of 12 general ophthalmologists and 10 retina
      specialists applied prespecified algorithms based on ICD-9-CM diagnosis codes to
      the billing claims of their practices and selected the associated medical
      records. Four ophthalmologists abstracted data from the medical records, which
      were then compared with the coded diagnoses. Main outcome measures were
      sensitivity, specificity, and the kappa statistic for the DME algorithm (a
      combination of codes 250.xx and 362.53), treating medical record documentation of
      DME as the standard criterion. RESULTS: The DME algorithm had a sensitivity of
      0.88 and a specificity of 0.96 for identifying DME. Excellent agreement was noted
      between the algorithm and the medical records (kappa = 0.84). The algorithm
      performed less well in identifying patients with a diagnosis of clinically
      significant DME (sensitivity, 0.86; specificity, 0.84; kappa = 0.64).
      CONCLUSIONS: The results of this pilot study suggest that patients with DME can
      be identified accurately in claims data using ICD-9-CM diagnosis codes.
      Application of this algorithm could improve investigations of disease prevalence
      and disease burden and provide an efficient means of assessing care and
      interventions.

PMID- 18625949
TI  - How much amblyopia treatment is enough?

PMID- 18625950
TI  - Vertical strabismus: diagnosis from the ground up.

PMID- 18625951
TI  - Treatment of acute optic neuritis: a summary of findings from the optic neuritis
      treatment trial.

PMID- 18625952
TI  - The optic neuritis treatment trial: a definitive answer and profound impact with
      unexpected results.

PMID- 18625954
TI  - Effect of intravitreous rituximab injections in patients with recurrent ocular
      lesions associated with central nervous system lymphoma.

PMID- 18625955
TI  - Corneal cupremia in multiple myeloma: a clinicopathologic correlation.

PMID- 18625956
TI  - Poliosis as a manifestation of conjunctival melanoma.

PMID- 18625957
TI  - Improved systemic chemotherapy for metastatic testicular choriocarcinoma can
      result in excellent prognosis for life and vision.

PMID- 18625958
TI  - Perivascular epithelioid cell tumor of the orbit.

PMID- 18625959
TI  - Teaching NeuroImage: nocardial intramedullary spinal cord abscess.

PMID- 18625961
TI  - Cannabis bliss? Perhaps not?

PMID- 18625962
TI  - Prolonged febrile seizures: underrecognized and perhaps underappreciated?

PMID- 18625963
TI  - KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes.
AB  - OBJECTIVE: To explore the involvement of M-type potassium channels KCNQ2, Q3, and
      Q5 in the pathogenesis of common idiopathic epilepsies. METHODS: Sequence
      analysis of the KCNQ2, Q3, and Q5 coding regions was performed in a screening
      sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an
      association study was conducted for all discovered variants in a case-control
      sample comprising 459 German patients with idiopathic generalized epilepsy (IGE)
      and 462 population controls. RESULTS: An in-frame deletion of codon 116 in KCNQ2
      (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two
      index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both
      mutations resulted in reduced potassium current amplitude in Xenopus oocytes.
      Mutation analysis of families with rolandic epilepsy without neonatal seizures
      discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val,
      KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant
      reduction of potassium current amplitude in Xenopus oocytes and was present only
      once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and
      p.Pro574Ser) were present in all affected family members and did not occur in
      controls, but did not show obvious functional abnormalities. The KCNQ3 missense
      variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454
      controls (p = 0.008). In KCNQ2, a silent single nucleotide polymorphism
      (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004).
      CONCLUSION: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to
      the etiology of common idiopathic epilepsy syndromes.

PMID- 18625964
TI  - Site of the ischemic penumbra as a predictor of potential for recovery of
      functions.
AB  - BACKGROUND AND PURPOSE: Diffusion-perfusion mismatch has been used to estimate
      salvageable tissue and predict potential for recovery in acute stroke. Location
      of the salvageable tissue may be as important as volume or percentage in
      predicting potential for recovery of specific functions. Impaired naming, a
      common and disabling deficit after left hemisphere stroke, is often associated
      with tissue dysfunction of left Brodmann area (BA) 37, posterior inferior
      temporal cortex. We tested the hypothesis that the presence of diffusion
      perfusion mismatch within left BA 37 predicts probability and extent of short
      term improvement of naming. METHODS: One hundred five patients with acute left
      hemisphere ischemic stroke had diffusion-weighted imaging, perfusion-weighted
      imaging, a test of picture naming, and other language tests at admission and 2 to
      4 days later. Linear regression was used to determine whether diffusion-perfusion
      mismatch in any BA in language cortex, total volume of mismatch, or diffusion or
      perfusion abnormality predicted degree of improvement in naming by days 3 to 5.
      RESULTS: The presence of >20% diffusion-perfusion mismatch in left BA 37 and
      total volumes of diffusion and perfusion abnormality at day 1 each independently
      predicted degree of improvement in naming. Mismatch in this area did not predict
      the degree of improvement in other language tests or the NIH Stroke Scale in this
      study. CONCLUSIONS/RELEVANCE: Diffusion-perfusion mismatch in left Brodmann area
      37 was strongly associated with acute improvement in naming, independently of
      volume or percentage of total mismatch or diffusion or perfusion abnormality.
      These data indicate that mismatch in a particular area is a marker of salvageable
      tissue and an important predictor of potential for recovery of functions that
      depend on that area. Location of mismatch before treatment may help to predict
      potential benefits of reperfusion.

PMID- 18625965
TI  - Metabolic syndrome and resistance to IV thrombolysis in middle cerebral artery
      ischemic stroke.
AB  - OBJECTIVE: The metabolic syndrome (MetS) is a cluster of vascular risk factors
      associated with a prothrombotic state. We aimed to evaluate the impact of MetS on
      the response to systemic tPA treatment in patients with acute middle cerebral
      artery (MCA) ischemic stroke. METHODS: We studied 100 consecutive patients with
      ischemic stroke with MCA occlusions on prebolus transcranial Doppler (TCD)
      examination treated with tPA following SITS-MOST criteria. MetS was diagnosed
      following AHA/NHLBI-2005 criteria. Resistance to thrombolysis was defined as the
      absence of TCD-assessed complete MCA recanalization 24 hours after tPA infusion.
      Infarct volume was measured on CT scans. Long-term clinical outcome was evaluated
      by the modified Rankin scale (mRS) score at day 90. RESULTS: Fifty-eight (58%)
      patients fulfilled MetS criteria. Median prebolus NIH Stroke Scale score was 17.
      Forty (42%) patients showed resistance to clot dissolution, and 53 (53%) had poor
      clinical outcomes (mRS > 2). A multivariable-adjusted logistic regression model
      identified MetS as independently associated with resistance to thrombolysis (OR
      4.7, 95% CI [1.7-13.6], p = 0.004). In the whole sample, MetS was associated with
      mRS > 2 (OR 2.4 [1.1-5.4], p = 0.03), although this association was no longer
      significant after multivariable adjustment. However, in patients with
      atherothrombotic stroke, MetS emerged as an independent predictor of poor long
      term outcome (adjusted OR 13.9 [1.3-148.7], p = 0.02). CONCLUSION: In our series,
      the metabolic syndrome was associated with a poor response to thrombolysis in
      patients with acute middle cerebral artery occlusions, as reflected by a higher
      resistance to clot dissolution.

PMID- 18625966
TI  - GD1b-specific antibody induces ataxia in Guillain-Barre syndrome.
AB  - BACKGROUND: Rabbit ataxic neuropathy and several case reports have suggested a
      close association of IgG anti-GD1b antibodies with ataxia in Guillain-Barre
      syndrome (GBS). However, about half of the patients with GBS having IgG anti-GD1b
      antibodies with no reactivities against other gangliosides (GD1b-mono IgG) do not
      exhibit ataxia. Antibodies specific to ganglioside complexes (GSCs) containing
      GD1b have been found in sera from some patients with GBS. OBJECTIVE: To
      investigate whether the reactivities of anti-GD1b IgG to such complexes are
      different between ataxic and nonataxic patients. METHODS: The authors examined
      sera from 17 patients with GBS (9 with ataxia and 8 without ataxia) who had GD1b
      mono IgG, with the use of an ELISA in which wells were coated with a mixture of
      GD1b and each of nine gangliosides (GM1, GM2, GM3, GD1a, GD3, GT1a, GT1b, GQ1b,
      and GalNAc-GD1a). The binding activities of the anti-GD1b IgG antibodies against
      such mixture antigens were compared between ataxic and nonataxic patients.
      RESULTS: The reactivities to antigens, such as GD1b combined with GD1a, GT1b,
      GQ1b, and GalNAc-GD1a, were significantly reduced in ataxic compared with
      nonataxic patients. Sera from all nonataxic patients had antibody activities to
      GSCs not containing GD1b. CONCLUSIONS: The addition of another ganglioside may
      cause conformational change of GD1b. Given the inhibition of the binding ability
      of the anti-GD1b IgG antibodies by such a conformational change, the anti-GD1b
      IgG antibodies in ataxic patients may interact closely with GD1b. IgG antibodies
      highly specific for GD1b may induce ataxia in Guillain-Barre syndrome.

PMID- 18625968
TI  - Descending monoaminergic pain modulation: bidirectional control and clinical
      relevance.

PMID- 18625967
TI  - Cardiorespiratory fitness and brain atrophy in early Alzheimer disease.
AB  - OBJECTIVE: To examine the correlation of cardiorespiratory fitness with brain
      atrophy and cognition in early-stage Alzheimer disease (AD). BACKGROUND: In
      normal aging physical fitness appears to mitigate functional and structural age
      related brain changes. Whether this is observed in AD is not known. METHODS:
      Subjects without dementia (n = 64) and subjects with early-stage AD (n = 57) had
      MRI and standard clinical and psychometric evaluations. Peak oxygen consumption
      (VO(2)(peak)), the standard measure of cardiorespiratory fitness, was assessed
      during a graded treadmill test. Normalized whole brain volume, a brain atrophy
      estimate, was determined by MRI. Pearson correlation and linear regression were
      used to assess fitness in relation to brain volume and cognitive performance.
      RESULTS: Cardiorespiratory fitness (VO(2)(peak)) was modestly reduced in subjects
      with AD (34.7 [5.0] mL/kg/min) vs subjects without dementia (38.1 [6.3]
      mL/kg/min, p = 0.002). In early AD, VO(2)(peak) was associated with whole brain
      volume (beta = 0.35, p = 0.02) and white matter volume (beta = 0.35, p = 0.04)
      after controlling for age. Controlling for additional covariates of sex, dementia
      severity, physical activity, and physical frailty did not attenuate the
      relationships. VO(2)(peak) was associated with performance on delayed memory and
      digit symbol in early AD but not after controlling for age. In participants with
      no dementia, there was no relationship between fitness and brain atrophy. Fitness
      in participants with no dementia was associated with better global cognitive
      performance (r = 0.30, p = 0.02) and performance on Trailmaking A and B, Stroop,
      and delayed logical memory but not after controlling for age. CONCLUSIONS:
      Increased cardiorespiratory fitness is associated with reduced brain atrophy in
      Alzheimer disease (AD). Cardiorespiratory fitness may moderate AD-related brain
      atrophy or a common underlying AD-related process may impact both brain atrophy
      and cardiorespiratory fitness.

PMID- 18625969
TI  - Susceptibility genes for restless legs syndrome are not associated with Parkinson
      disease.

PMID- 18625970
TI  - Celiac antibodies in the diagnostic workup of white matter lesions.

PMID- 18625971
TI  - A reversible cause of "vascular dementia".

PMID- 18625972
TI  - Significant association between leukoaraiosis and metabolic syndrome in healthy
      subjects.

PMID- 18625973
TI  - International science at the annual meeting of the American Academy of Neurology.

PMID- 18625974
TI  - Direct-to-consumer advertising: end the compromise.

PMID- 18625975
TI  - The missing link in tobacco control.

PMID- 18625979
TI  - Public-private health care delivery becoming the norm in Sweden.

PMID- 18625982
TI  - Congo cease fire brings little relief for women.

PMID- 18625985
TI  - Intentions of smokers to use free nicotine replacement therapy.
AB  - Public health initiatives to distribute nicotine replacement therapy free of
      charge as a means of promoting smoking cessation are ongoing. Are there enough
      smokers interested in using nicotine replacement therapy to have a substantial
      impact on the prevalence of smoking if this aid were distributed free to all
      interested smokers? We conducted a telephone survey of 825 randomly selected
      daily smokers aged 18 years or older who had smoked at least 10 cigarettes per
      day at some point in their lives. Overall, 58.9% of the respondents said they
      would be interested in nicotine replacement therapy if it were offered for free.
      Of those interested, almost all (93.8%) said that they would use the nicotine
      replacement therapy to help them quit for good. There were differences in the
      levels of interest: smokers who intended to quit were more interested in using
      the nicotine replacement therapy than those who planned to reduce or maintain
      their smoking.

PMID- 18625984
TI  - Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Many placebo-controlled trials have demonstrated the efficacy of
      individual pharmacotherapies approved for smoking cessation. However, few direct
      or indirect comparisons of such interventions have been conducted. We performed a
      meta-analysis to compare the treatment effects of 7 approved pharmacologic
      interventions for smoking cessation. METHODS: We searched the US Centers for
      Disease Control and Prevention's Tobacco Information and Prevention database as
      well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo
      controlled, double-blind randomized controlled trials of pharmacotherapies for
      smoking cessation. We included studies that reported biochemically validated
      measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random
      effects model to summarize the results for each intervention. RESULTS: We
      identified 70 published reports of 69 trials involving a total of 32 908
      patients. Six of the 7 pharmacotherapies studied were found to be more
      efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible
      interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13),
      bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI
      1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR
      1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which
      measure of abstinence was used. Although the point estimate favoured nicotine
      inhaler over placebo (OR 2.17), these results were not conclusive because the
      credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions
      were included in the same model, all were more efficacious than placebo. In our
      analysis of data from the varenicline trials that included bupropion control
      arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09
      4.08). INTERPRETATION: Varenicline, bupropion and the 5 nicotine replacement
      therapies were all more efficacious than placebo at promoting smoking abstinence
      at 6 and 12 months.

PMID- 18625986
TI  - Quality of indoor residential air and health.
AB  - About 90% of our time is spent indoors where we are exposed to chemical and
      biological contaminants and possibly to carcinogens. These agents may influence
      the risk of developing nonspecific respiratory and neurologic symptoms,
      allergies, asthma and lung cancer. We review the sources, health effects and
      control strategies for several of these agents. There are conflicting data about
      indoor allergens. Early exposure may increase or may decrease the risk of future
      sensitization. Reports of indoor moulds or dampness or both are consistently
      associated with increased respiratory symptoms but causality has not been
      established. After cigarette smoking, exposure to environmental tobacco smoke and
      radon are the most common causes of lung cancer. Homeowners can improve the air
      quality in their homes, often with relatively simple measures, which should
      provide health benefits.

PMID- 18625987
TI  - Hospital mortality: when failure is not a good measure of success.

PMID- 18625988
TI  - Caterpillar-induced bleeding syndrome in a returning traveller.

PMID- 18625989
TI  - Watermelon stomach.

PMID- 18625991
TI  - Disease surveillance.

PMID- 18625992
TI  - Missed opportunity.

PMID- 18625993
TI  - Dangers for children in the care of drug users.

PMID- 18625994
TI  - Distressing news on the Therapeutics Initiative.

PMID- 18625999
TI  - Gallstone ileus.

PMID- 18626001
TI  - Cardiovascular risk profile and subsequent disability and mental well-being: the
      Zutphen Elderly Study.
AB  - OBJECTIVES: It is insufficiently known whether "classic" cardiovascular risk
      factors are associated with subsequent functional disability and mental well
      being in elderly men. DESIGN: A population-based cohort study with 15 years of
      follow-up from 1985 onward. SETTING: The Zutphen Study started as the Dutch
      contribution to the Seven Countries Study. PARTICIPANTS: Five hundred forty-five
      (59.2%) of 887 men (aged 64-84 years) who were free of preexisting cardiovascular
      disease and cancer. MEASUREMENTS: High cardiovascular risk was defined as having
      >/=2 "classic" risk factors: body mass index >/=30.0 kg/m(2), presently smoking,
      hypertension (systolic blood pressure >/=160 mm Hg, diastolic blood pressure
      >/=95 mm Hg, or antihypertensive medication), serum cholesterol >/=6.5 mmol/L,
      and diabetes mellitus. Self-rated health and dispositional optimism were assessed
      in 1985, 1990, 1995, and 2000. Disability and depressive symptoms (by the Zung
      self-rating depression scale) were assessed from 1990 onward. RESULTS: The high
      risk (N = 230) versus low-risk group (N = 315) had higher multivariate adjusted
      risks of all-cause and cardiovascular mortality (hazard ratios: 1.43; confidence
      interval[CI]: 1.15, 1.76; and 1.61; CI: 1.20, 2.18, respectively). High-risk
      status was also associated with more functional disability at 5, 10, and 15 years
      (odds ratios of 2.00, 95% CI: 1.25-3.20; 2.51, 95% CI: 1.36-4.65; and 2.45, 95%
      CI: 0.91-6.61, respectively), adjusted for baseline age, self-rated health, and
      dispositional optimism. Risk status was not associated with self-rated health,
      dispositional optimism, or depressive symptoms at follow-up. CONCLUSION: Combined
      "classic" cardiovascular risk factors are not associated with impaired self-rated
      health or mental well-being in elderly men, but are predictive of functional
      disability.

PMID- 18626002
TI  - Brain lithium levels and effects on cognition and mood in geriatric bipolar
      disorder: a lithium-7 magnetic resonance spectroscopy study.
AB  - OBJECTIVES: The authors investigated the relationship between brain lithium,
      serum lithium and age in adult subjects treated with lithium. In addition, the
      authors investigated the association between brain lithium and serum lithium with
      frontal lobe functioning and mood in a subgroup of older subjects. DESIGN: Cross
      sectional assessment. SETTING: McLean Hospital's Geriatric Psychiatry Research
      Program and Brain Imaging Center; The Division of Psychiatry, Boston University
      School of Medicine. PARTICIPANTS: Twenty-six subjects, 20 to 85 years, with
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-TR bipolar
      disorder (BD), currently treated with lithium. MEASUREMENTS: All subjects had
      measurements of mood (Hamilton Depression Rating Scale [HDRS] and Young Mania
      Rating Scale) and serum and brain lithium levels. Brain lithium levels were
      assessed using lithium Magnetic Resonance Spectroscopy. Ten subjects older than
      50 years also had assessments of frontal lobe functioning (Stroop, Trails A and
      B, Wis. Card Sorting Task). RESULTS: Brain lithium levels correlated with serum
      lithium levels for the group as a whole. However, this relationship was not
      present for the group of subjects older than 50. For these older subjects
      elevations in brain (but not serum) lithium levels were associated with frontal
      lobe dysfunction and higher HDRS scores. The higher HDRS were associated with
      increased somatic symptoms. CONCLUSION: Frontal lobe dysfunction and elevated
      depression symptoms correlating with higher brain lithium levels supports
      conservative dosing recommendations in bipolar older adults. The absence of a
      predictable relationship between serum and brain lithium makes specific
      individual predictions about the "ideal" lithium serum level in an older adult
      with BD difficult.

PMID- 18626003
TI  - Prostate cancer: moving forward by reinventing the wheel...but this time it is
      round.

PMID- 18626004
TI  - Phase II multicenter study of bendamustine plus rituximab in patients with
      relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma.
AB  - PURPOSE: Bendamustine HCl is a bifunctional mechlorethamine derivative with
      clinical activity in the treatment of non-Hodgkin's lymphoma. This study
      evaluated bendamustine plus rituximab in 67 adults with relapsed, indolent B-cell
      or mantle cell lymphoma without documented resistance to prior rituximab.
      PATIENTS AND METHODS: Patients received rituximab 375 mg/m(2) intravenously on
      day 1 and bendamustine 90 mg/m(2) intravenously on days 2 and 3 of each 28-day
      cycle for four to six cycles. An additional dose of rituximab was administered 1
      week before the first cycle and 4 weeks after the last cycle. Sixty-six patients
      (median age, 60 years) received at least one dose of both drugs. RESULTS: Overall
      response rate was 92% (41% complete response, 14% unconfirmed complete response,
      and 38% partial response). Median duration of response was 21 months (95% CI, 18
      to 24 months). Median progression-free survival time was 23 months (95% CI, 20 to
      26 months). Outcomes were similar for patients with indolent or mantle cell
      histologies. The combination was generally well tolerated; the primary toxicity
      was myelosuppression (grade 3 or 4 neutropenia, 36%; grade 3 or 4
      thrombocytopenia, 9%). CONCLUSION: Bendamustine plus rituximab is an active
      combination in patients with relapsed indolent and mantle cell lymphoma.

PMID- 18626005
TI  - International peripheral T-cell and natural killer/T-cell lymphoma study:
      pathology findings and clinical outcomes.
AB  - PURPOSE: Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma
      (NKTCL) are rare and heterogeneous forms of non-Hodgkin's lymphoma (NHL) that, in
      general, are associated with a poor clinical outcome. PATIENTS AND METHODS: A
      cohort of 1,314 cases of PTCL and NKTCL was organized from 22 centers worldwide,
      consisting of patients with previously untreated PTCL or NKTCL who were diagnosed
      between 1990 and 2002. Tissue biopsies, immunophenotypic markers, molecular
      genetic studies, and clinical information from consecutive patients at each site
      were reviewed by panels of four expert hematopathologists and classified
      according to the WHO classification. RESULTS: A diagnosis of PTCL or NKTCL was
      confirmed in 1,153 (87.8%) of the cases. The most common subtypes were PTCL not
      otherwise specified (NOS; 25.9%), angioimmunoblastic type (18.5%), NKTCL (10.4%),
      and adult T-cell leukemia/lymphoma (ATLL; 9.6%). Misclassification occurred in
      10.4% of the cases including Hodgkin's lymphoma (3%), B-cell lymphoma (1.4%),
      unclassifiable lymphoma (2.8%), or a diagnosis other than lymphoma (2.3%). We
      found marked variation in the frequency of the various subtypes by geographic
      region. The use of an anthracycline-containing regimen was not associated with an
      improved outcome in PTCL-NOS or angioimmunoblastic type, but was associated with
      an improved outcome in anaplastic large-cell lymphoma, ALK positive. CONCLUSION:
      The WHO classification is useful for defining subtypes of PTCL and NKTCL.
      However, expert hematopathology review is important for accurate diagnosis. The
      clinical outcome for patients with most of these lymphoma subtypes is poor with
      standard therapies, and novel agents and new modalities are needed to improve
      survival.

PMID- 18626006
TI  - Tumor metabolism and blood flow changes by positron emission tomography: relation
      to survival in patients treated with neoadjuvant chemotherapy for locally
      advanced breast cancer.
AB  - PURPOSE: Patients with locally advanced breast carcinoma (LABC) receive
      preoperative chemotherapy to provide early systemic treatment and assess in vivo
      tumor response. Serial positron emission tomography (PET) has been shown to
      predict pathologic response in this setting. We evaluated serial quantitative PET
      tumor blood flow (BF) and metabolism as in vivo measurements to predict patient
      outcome. PATIENTS AND METHODS: Fifty-three women with primary LABC underwent
      dynamic [(18)F]fluorodeoxyglucose (FDG) and [(15)O]water PET scans before and at
      midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG) and
      transport (FDG K(1)) parameters were calculated; BF was estimated from the
      [(15)O]water study. Associations between BF, MRFDG, FDG K(1), and standardized
      uptake value and disease-free survival (DFS) and overall survival (OS) were
      evaluated using the Cox proportional hazards model. RESULTS: Patients with
      persistent or elevated BF and FDG K(1) from baseline to midtherapy had higher
      recurrence and mortality risks than patients with reductions. In multivariable
      analyses, BF and FDG K(1) changes remained independent prognosticators of DFS and
      OS. For example, in the association between BF and mortality, a patient with a 5%
      increase in tumor BF had a 67% higher mortality risk compared with a patient with
      a 5% decrease in tumor BF (hazard ratio = 1.67; 95% CI, 1.24 to 2.24; P < .001).
      CONCLUSION: LABC patients with limited or no decline in BF and FDG K(1)
      experienced higher recurrence and mortality risks that were greater than the
      effects of clinical tumor characteristics. Tumor perfusion changes over the
      course of neoadjuvant chemotherapy measured directly by [(15)O]water or
      indirectly by dynamic FDG predict DFS and OS.

PMID- 18626007
TI  - Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer
      Institute of Canada Clinical Trials Group Study BR.21.
AB  - PURPOSE: To evaluate the effect of KRAS and epidermal growth factor receptor
      (EGFR) genotype on the response to erlotinib treatment in the BR.21, placebo
      controlled trial. PATIENTS AND METHODS: We analyzed 206 tumors for KRAS mutation,
      204 tumors for EGFR mutation, and 159 tumors for EGFR gene copy by fluorescent in
      situ hybridization (FISH). We reanalyzed EGFR deletion/mutation using two highly
      sensitive techniques that detect abnormalities in samples with 5% to 10% tumor
      cellularity. KRAS mutation was analyzed by direct sequencing. RESULTS: Thirty
      patients (15%) had KRAS mutations, 34 (17%) had EGFR exon 19 deletion or exon 21
      L858R mutations, and 61 (38%) had high EGFR gene copy (FISH positive). Response
      rates were 10% for wild-type and 5% for mutant KRAS (P = .69), 7% for wild-type
      and 27% for mutant EGFR (P = .03), and 5% for EGFR FISH-negative and 21% for FISH
      positive patients (P = .02). Significant survival benefit from erlotinib therapy
      was observed for patients with wild-type KRAS (hazard ratio [HR] = 0.69, P = .03)
      and EGFR FISH positivity (HR = 0.43, P = .004) but not for patients with mutant
      KRAS (HR = 1.67, P = .31), wild-type EGFR (HR = 0.74, P = .09), mutant EGFR (HR =
      0.55, P = .12), and EGFR FISH negativity (HR = 0.80, P = .35). In multivariate
      analysis, only EGFR FISH-positive status was prognostic for poorer survival (P =
      .025) and predictive of differential survival benefit from erlotinib (P = .005).
      CONCLUSION: EGFR mutations and high copy number are predictive of response to
      erlotinib. EGFR FISH is the strongest prognostic marker and a significant
      predictive marker of differential survival benefit from erlotinib.

PMID- 18626008
TI  - Climate-related increase in the prevalence of urolithiasis in the United States.
AB  - An unanticipated result of global warming is the likely northward expansion of
      the present-day southeastern U.S. kidney stone "belt." The fraction of the U.S.
      population living in high-risk zones for nephrolithiasis will grow from 40% in
      2000 to 56% by 2050, and to 70% by 2095. Predictions based on a climate model of
      intermediate severity warming (SRESa1b) indicate a climate-related increase of
      1.6-2.2 million lifetime cases of nephrolithiasis by 2050, representing up to a
      30% increase in some climate divisions. Nationwide, the cost increase associated
      with this rise in nephrolithiasis would be $0.9-1.3 billion annually (year-2000
      dollars), representing a 25% increase over current expenditures. The impact of
      these changes will be geographically concentrated, depending on the precise
      relationship between temperature and stone risk. Stone risk may abruptly increase
      at a threshold temperature (nonlinear model) or increase steadily with
      temperature change (linear model) or some combination thereof. The linear model
      predicts increases by 2050 that are concentrated in California, Texas, Florida,
      and the Eastern Seaboard; the nonlinear model predicts concentration in a
      geographic band stretching from Kansas to Kentucky and Northern California,
      immediately south of the threshold isotherm.

PMID- 18626009
TI  - RNA binding activity of the recessive parkinsonism protein DJ-1 supports
      involvement in multiple cellular pathways.
AB  - Parkinson's disease (PD) is a major neurodegenerative condition with several rare
      Mendelian forms. Oxidative stress and mitochondrial function have been implicated
      in the pathogenesis of PD but the molecular mechanisms involved in the
      degeneration of neurons remain unclear. DJ-1 mutations are one cause of recessive
      parkinsonism, but this gene is also reported to be involved in cancer by
      promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific
      function of DJ-1 is unknown, although it is responsive to oxidative stress and
      may play a role in the maintenance of mitochondria. Here, we show, using four
      independent methods, that DJ-1 associates with RNA targets in cells and the
      brain, including mitochondrial genes, genes involved in glutathione metabolism,
      and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient
      in this activity. We show that DJ-1 is sufficient for RNA binding at nanomolar
      concentrations. Further, we show that DJ-1 binds RNA but dissociates after
      oxidative stress. These data implicate a single mechanism for the pleiotropic
      effects of DJ-1 in different model systems, namely that the protein binds
      multiple RNA targets in an oxidation-dependent manner.

PMID- 18626010
TI  - Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor
      gating that can be reversed with antipsychotic treatment.
AB  - Regulated intramembrane proteolysis by gamma-secretase cleaves proteins in their
      transmembrane domain and is involved in important signaling pathways. At least
      four different gamma-secretase complexes have been identified, but little is
      known about their biological role and specificity. Previous work has demonstrated
      the involvement of the Aph1A-gamma-secretase complex in Notch signaling, but no
      specific function could be assigned to Aph1B/C-gamma-secretase. We demonstrate
      here that the Aph1B/C-gamma-secretase complex is expressed in brain areas
      relevant to schizophrenia pathogenesis and that Aph1B/C deficiency causes
      pharmacological and behavioral abnormalities that can be reversed by
      antipsychotic drugs. At the molecular level we find accumulation of Nrg1
      fragments in the brain of Aph1BC(-/-) mice. Our observations gain clinical
      relevance by the demonstration that a Val-to-Leu mutation in the Nrg1
      transmembrane domain, associated with increased risk for schizophrenia, affects
      gamma-secretase cleavage of Nrg1. This finding suggests that dysregulation of
      intramembrane proteolysis of Nrg1 could increase risk for schizophrenia and
      related disorders.

PMID- 18626011
TI  - Microsatellites as EWS/FLI response elements in Ewing's sarcoma.
AB  - The ETS gene family is frequently involved in chromosome translocations that
      cause human cancer, including prostate cancer, leukemia, and sarcoma. However,
      the mechanisms by which oncogenic ETS proteins, which are DNA-binding
      transcription factors, target genes necessary for tumorigenesis is not well
      understood. Ewing's sarcoma serves as a paradigm for the entire class of ETS
      associated tumors because nearly all cases harbor recurrent chromosomal
      translocations involving ETS genes. The most common translocation in Ewing's
      sarcoma encodes the EWS/FLI oncogenic transcription factor. We used whole genome
      localization (ChIP-chip) to identify target genes that are directly bound by
      EWS/FLI. Analysis of the promoters of these genes demonstrated a significant over
      representation of highly repetitive GGAA-containing elements (microsatellites).
      In a parallel approach, we found that EWS/FLI uses GGAA microsatellites to
      regulate the expression of some of its target genes including NR0B1, a gene
      required for Ewing's sarcoma oncogenesis. The microsatellite in the NR0B1
      promoter bound EWS/FLI in vitro and in vivo and was both necessary and sufficient
      to confer EWS/FLI regulation to a reporter gene. Genome wide computational
      studies demonstrated that GGAA microsatellites were enriched close to EWS/FLI-up
      regulated genes but not down-regulated genes. Mechanistic studies demonstrated
      that the ability of EWS/FLI to bind DNA and modulate gene expression through
      these repetitive elements depended on the number of consecutive GGAA motifs.
      These findings illustrate an unprecedented route to specificity for ETS proteins
      and use of microsatellites in tumorigenesis.

PMID- 18626012
TI  - Preprocalcitonin signal peptide generates a cytotoxic T lymphocyte-defined tumor
      epitope processed by a proteasome-independent pathway.
AB  - We identified an antigen recognized on a human non-small-cell lung carcinoma by a
      cytotoxic T lymphocyte clone derived from autologous tumor-infiltrating
      lymphocytes. The antigenic peptide is presented by HLA-A2 and is encoded by the
      CALCA gene, which codes for calcitonin and for the alpha-calcitonin gene-related
      peptide. The peptide is derived from the carboxy-terminal region of the
      preprocalcitonin signal peptide and is processed independently of proteasomes and
      the transporter associated with antigen processing. Processing occurs within the
      endoplasmic reticulum of all tumoral and normal cells tested, including dendritic
      cells, and it involves signal peptidase and the aspartic protease, signal peptide
      peptidase. The CALCA gene is overexpressed in medullary thyroid carcinomas and in
      several lung carcinomas compared with normal tissues, leading to recognition by
      the T cell clone. This new epitope is, therefore, a promising candidate for
      cancer immunotherapy.

PMID- 18626013
TI  - Carbon dioxide sequestration in deep-sea basalt.
AB  - Developing a method for secure sequestration of anthropogenic carbon dioxide in
      geological formations is one of our most pressing global scientific problems.
      Injection into deep-sea basalt formations provides unique and significant
      advantages over other potential geological storage options, including (i) vast
      reservoir capacities sufficient to accommodate centuries-long U.S. production of
      fossil fuel CO2 at locations within pipeline distances to populated areas and CO2
      sources along the U.S. west coast; (ii) sufficiently closed water-rock
      circulation pathways for the chemical reaction of CO2 with basalt to produce
      stable and nontoxic (Ca(2+), Mg(2+), Fe(2+))CO(3) infilling minerals, and (iii)
      significant risk reduction for post-injection leakage by geological,
      gravitational, and hydrate-trapping mechanisms. CO2 sequestration in established
      sediment-covered basalt aquifers on the Juan de Fuca plate offer promising
      locations to securely accommodate more than a century of future U.S. emissions,
      warranting energized scientific research, technological assessment, and economic
      evaluation to establish a viable pilot injection program in the future.

PMID- 18626014
TI  - uORFs with unusual translational start codons autoregulate expression of
      eukaryotic ornithine decarboxylase homologs.
AB  - In a minority of eukaryotic mRNAs, a small functional upstream ORF (uORF), often
      performing a regulatory role, precedes the translation start site for the main
      product(s). Here, conserved uORFs in numerous ornithine decarboxylase homologs
      are identified from yeast to mammals. Most have noncanonical evolutionarily
      conserved start codons, the main one being AUU, which has not been known as an
      initiator for eukaryotic chromosomal genes. The AUG-less uORF present in mouse
      antizyme inhibitor, one of the ornithine decarboxylase homologs in mammals,
      mediates polyamine-induced repression of the downstream main ORF. This repression
      is part of an autoregulatory circuit, and one of its sensors is the AUU codon,
      which suggests that translation initiation codon identity is likely used for
      regulation in eukaryotes.

PMID- 18626015
TI  - Theoretical studies on bimolecular reaction dynamics.
AB  - This perspective discusses progress in the theory of bimolecular reaction
      dynamics in the gas phase. The examples selected show that definitive quantum
      dynamical computations are providing insights into the detailed mechanisms of
      chemical reactions.

PMID- 18626016
TI  - Quantification of the infectious dose of Leishmania major transmitted to the skin
      by single sand flies.
AB  - Leishmaniasis is transmitted between mammalian hosts by the bites of bloodsucking
      vector sand flies. The dose of parasites transmitted to the mammalian host has
      never been directly determined. We developed a real-time PCR-based method to
      determine the number of Leishmania major parasites inoculated into the ears of
      living mice during feeding by individual infected flies (Phlebotomus duboscqi).
      The number of parasites transmitted varied over a wide range in the 58 ears in
      which Leishmania were detected and demonstrated a clear bimodal distribution.
      Most of the infected mice were inoculated with a low dose of <600 parasites. One
      in four received a higher dose of >1,000 and up to 100,000 cells. High-dose
      transmission was associated with a heavy midgut infection of >30,000 parasites,
      incomplete blood feeding, and transmission of a high percentage of the parasite
      load in the fly. To test the impact of inoculum size on infection outcome, we
      compared representative high- (5,000) and low- (100) dose intradermal needle
      infections in the ears of C57BL/6 mice. To mimic natural transmission, we used
      sand fly-derived metacyclic forms of L. major and preexposed the injection site
      to the bites of uninfected flies. Large lesions developed rapidly in the ears of
      mice receiving the high-dose inoculum. The low dose resulted in only minor
      pathology but a higher parasite titer in the chronic phase, and it established
      the host as an efficient long-term reservoir of infection back to vector sand
      flies.

PMID- 18626017
TI  - Male-derived butterfly anti-aphrodisiac mediates induced indirect plant defense.
AB  - Plants can recruit parasitic wasps in response to egg deposition by herbivorous
      insects-a sophisticated indirect plant defense mechanism. Oviposition by the
      Large Cabbage White butterfly Pieris brassicae on Brussels sprout plants induces
      phytochemical changes that arrest the egg parasitoid Trichogramma brassicae.
      Here, we report the identification of an elicitor of such an oviposition-induced
      plant response. Eliciting activity was present in accessory gland secretions
      released by mated female butterflies during egg deposition. In contrast, gland
      secretions from virgin female butterflies were inactive. In the male ejaculate,
      P. brassicae females receive the anti-aphrodisiac benzyl cyanide (BC) that
      reduces the females' attractiveness for subsequent mating. We detected this
      pheromone in the accessory gland secretion released by mated female butterflies.
      When applied onto leaves, BC alone induced phytochemical changes that arrested
      females of the egg parasitoid. Microarray analyses revealed a similarity in
      induced plant responses that may explain the arrest of T. brassicae to egg-laden
      and BC-treated plants. Thus, a male-derived compound endangers the offspring of
      the butterfly by inducing plant defense. Recently, BC was shown to play a role in
      foraging behavior of T. brassicae, by acting as a cue to facilitate phoretic
      transport by mated female butterflies to oviposition sites. Our results suggest
      that the anti-aphrodisiac pheromone incurs fitness costs for the butterfly by
      both mediating phoretic behavior and inducing plant defense.

PMID- 18626018
TI  - Glucose controls CREB activity in islet cells via regulated phosphorylation of
      TORC2.
AB  - CREB is a cAMP- and calcium-responsive transcriptional activator that is required
      for islet beta cell proliferation and survival. Glucose and incretin hormones
      elicit beta cell insulin secretion and promote synergistic CREB activity by
      inducing the nuclear relocalization of TORC2 (also known as Crtc2), a coactivator
      for CREB. In islet cells under basal conditions when CREB activity is low, TORC2
      is phosphorylated and sequestered in the cytoplasm by 14-3-3 proteins. In
      response to feeding stimuli, TORC2 is dephosphorylated, enters the nucleus, and
      binds to CREB located at target gene promoters. The dephosphorylation of TORC2 at
      Ser-171 in response to cAMP is insufficient to account for the dynamics of TORC2
      localization and CREB activity in islet cells. Here, we identify Ser-275 of TORC2
      as a 14-3-3 binding site that is phosphorylated under low glucose conditions and
      which becomes dephosphorylated by calcineurin in response to glucose influx.
      Dephosphorylation of Ser-275 is essential for both glucose and cAMP-mediated
      activation of CREB in beta cells and islets. Using a cell-based screen of 180
      human protein kinases, we identified MARK2, a member of the AMPK family of
      Ser/Thr kinases, as a Ser-275 kinase that blocks TORC2:CREB activity. Taken
      together, these data provide the mechanistic underpinning for how cAMP and
      glucose cooperatively promote a transcriptional program critical for islet cell
      survival, and identifies MARK2 as a potential target for diabetes treatment.

PMID- 18626019
TI  - Theoretical and experimental demonstration of the importance of specific
      nonnative interactions in protein folding.
AB  - Many experimental and theoretical studies have suggested a significant role for
      nonnative interactions in protein folding pathways, but the energetic
      contributions of these interactions are not well understood. We have addressed
      the energetics and the position specificity of nonnative hydrophobic interactions
      by developing a continuum coarse-grained chain model with a native-centric
      potential augmented by sequence-dependent hydrophobic interactions. By modeling
      the effect of different hydrophobicity values at various positions in the Fyn SH3
      domain, we predicted energetically significant nonnative interactions that led to
      acceleration or deceleration of the folding rate depending on whether they were
      more populated in the transition state or unfolded state. These nonnative
      contacts were centered on position 53 in the Fyn SH3 domain, which lies in an
      exposed position in a 3(10)-helix. The energetic importance of the predicted
      nonnative interactions was confirmed experimentally by folding kinetics studies
      combined with double mutant thermodynamic cycles. By attaining agreement of
      theoretical and experimental investigations, this study provides a compelling
      demonstration that specific nonnative interactions can significantly influence
      folding energetics. Moreover, we show that a coarse-grained model with a simple
      consideration of hydrophobicity is sufficient for the accurate prediction of
      kinetically important nonnative interactions.

PMID- 18626020
TI  - Transporters of arsenite in rice and their role in arsenic accumulation in rice
      grain.
AB  - Arsenic poisoning affects millions of people worldwide. Human arsenic intake from
      rice consumption can be substantial because rice is particularly efficient in
      assimilating arsenic from paddy soils, although the mechanism has not been
      elucidated. Here we report that two different types of transporters mediate
      transport of arsenite, the predominant form of arsenic in paddy soil, from the
      external medium to the xylem. Transporters belonging to the NIP subfamily of
      aquaporins in rice are permeable to arsenite but not to arsenate. Mutation in
      OsNIP2;1 (Lsi1, a silicon influx transporter) significantly decreases arsenite
      uptake. Furthermore, in the rice mutants defective in the silicon efflux
      transporter Lsi2, arsenite transport to the xylem and accumulation in shoots and
      grain decreased greatly. Mutation in Lsi2 had a much greater impact on arsenic
      accumulation in shoots and grain in field-grown rice than Lsi1. Arsenite
      transport in rice roots therefore shares the same highly efficient pathway as
      silicon, which explains why rice is efficient in arsenic accumulation. Our
      results provide insight into the uptake mechanism of arsenite in rice and
      strategies for reducing arsenic accumulation in grain for enhanced food safety.

PMID- 18626021
TI  - Conserved T cell receptor alpha-chain induces insulin autoantibodies.
AB  - A fundamental question is what are the molecular determinants that lead to
      spontaneous preferential targeting of specific autoantigens in autoimmune
      diseases, such as the insulin B:9-23 peptide sequence in type 1 diabetes. Anti
      insulin B:9-23 T cell clones isolated from prediabetic NOD islets have a
      conserved Valpha-segment/Jalpha-segment, but no conservation of the alpha-chain N
      region and no conservation of the Vbeta-chain. Here, we show that the conserved T
      cell receptor alpha-chain generates insulin autoantibodies when transgenically or
      retrogenically introduced into mice without its corresponding Vbeta. We suggest
      that a major part of the mystery as to why islet autoimmunity develops relates to
      recognition of a primary insulin peptide by a conserved alpha chain T cell
      receptor.

PMID- 18626022
TI  - The role of microtubule movement in bidirectional organelle transport.
AB  - We study the role of microtubule movement in bidirectional organelle transport in
      Drosophila S2 cells and show that EGFP-tagged peroxisomes in cells serve as
      sensitive probes of motor induced, noisy cytoskeletal motions. Multiple
      peroxisomes move in unison over large time windows and show correlations with
      microtubule tip positions, indicating rapid microtubule fluctuations in the
      longitudinal direction. We report the first high-resolution measurement of
      longitudinal microtubule fluctuations performed by tracing such pairs of co
      moving peroxisomes. The resulting picture shows that motor-dependent longitudinal
      microtubule oscillations contribute significantly to cargo movement along
      microtubules. Thus, contrary to the conventional view, organelle transport cannot
      be described solely in terms of cargo movement along stationary microtubule
      tracks, but instead includes a strong contribution from the movement of the
      tracks.

PMID- 18626024
TI  - Quantum percolation in cuprate high-temperature superconductors.
AB  - Although it is now generally acknowledged that electron-phonon interactions cause
      cuprate superconductivity with T(c) values approximately 100 K, the complexities
      of atomic arrangements in these marginally stable multilayer materials have
      frustrated both experimental analysis and theoretical modeling of the remarkably
      rich data obtained both by angle-resolved photoemission (ARPES) and high
      resolution, large-area scanning tunneling microscopy (STM). Here, we analyze the
      theoretical background in terms of our original (1989) model of dopant-assisted
      quantum percolation (DAQP), as developed further in some two dozen articles, and
      apply these ideas to recent STM data. We conclude that despite all of the many
      difficulties, with improved data analysis it may yet be possible to identify
      quantum percolative paths.

PMID- 18626023
TI  - A pathogenic dyskerin mutation impairs proliferation and activates a DNA damage
      response independent of telomere length in mice.
AB  - Telomeres are nucleoprotein structures that cap the ends of chromosomes,
      protecting them from exonucleases and distinguishing them from double-stranded
      breaks. Their integrity is maintained by telomerase, an enzyme consisting of a
      reverse transcriptase, TERT and an RNA template, TERC, and other components,
      including the pseudouridine synthase, dyskerin, the product of the DKC1 gene.
      When telomeres become critically short, a p53-dependent pathway causing cell
      cycle arrest is induced that can lead to senescence, apoptosis, or, rarely to
      genomic instability and transformation. The same pathway is induced in response
      to DNA damage. DKC1 mutations in the disease dyskeratosis congenita are thought
      to act via this mechanism, causing growth defects in proliferative tissues
      through telomere shortening. Here, we show that pathogenic mutations in mouse
      Dkc1 cause a growth disadvantage and an enhanced DNA damage response in the
      context of telomeres of normal length. We show by genetic experiments that the
      growth disadvantage, detected by disparities in X-inactivation patterns in female
      heterozygotes, depends on telomerase. Hemizygous male mutant cells showed a
      strikingly enhanced DNA damage response via the ATM/p53 pathway after treatment
      with etoposide with a significant number of DNA damage foci colocalizing with
      telomeres in cytological preparations. We conclude that dyskerin mutations cause
      slow growth independently of telomere shortening and that this slow growth is the
      result of the induction of DNA damage. Thus, dyskerin interacts with telomerase
      and affects telomere maintenance independently of telomere length.

PMID- 18626025
TI  - Conceptual knowledge increases infants' memory capacity.
AB  - Adults can expand their limited working memory capacity by using stored
      conceptual knowledge to chunk items into interrelated units. For example, adults
      are better at remembering the letter string PBSBBCCNN after parsing it into three
      smaller units: the television acronyms PBS, BBC, and CNN. Is this chunking a
      learned strategy acquired through instruction? We explored the origins of this
      ability by asking whether untrained infants can use conceptual knowledge to
      increase memory. In the absence of any grouping cues, 14-month-old infants can
      track only three hidden objects at once, demonstrating the standard limit of
      working memory. In four experiments we show that infants can surpass this limit
      when given perceptual, conceptual, linguistic, or spatial cues to parse larger
      arrays into smaller units that are more efficiently stored in memory. This work
      offers evidence of memory expansion based on conceptual knowledge in untrained,
      preverbal subjects. Our findings demonstrate that without instruction, and in the
      absence of robust language, a fundamental memory computation is available
      throughout the lifespan, years before the development of explicit metamemorial
      strategies.

PMID- 18626026
TI  - Life-history change in disease-ravaged Tasmanian devil populations.
AB  - Changes in life history are expected when new sources of extrinsic mortality
      impact on natural populations. We report a new disease, devil facial tumor
      disease, causing an abrupt transition from iteroparity toward single breeding in
      the largest extant carnivorous marsupial, the Tasmanian devil (Sarcophilus
      harrisii), in which males can weigh as much as 14 kg and females 9 kg. This
      change in life history is associated with almost complete mortality of
      individuals from this infectious cancer past their first year of adult life.
      Devils have shown their capacity to respond to this disease-induced increased
      adult mortality with a 16-fold increase in the proportion of individuals
      exhibiting precocious sexual maturity. These patterns are documented in five
      populations where there are data from before and after disease arrival and
      subsequent population impacts. To our knowledge, this is the first known case of
      infectious disease leading to increased early reproduction in a mammal. The
      persistence of both this disease and the associated life-history changes pose
      questions about longer-term evolutionary responses and conservation prospects for
      this iconic species.

PMID- 18626027
TI  - North Carolina medicaid: a fruitful payer-practice collaboration.

PMID- 18626028
TI  - Integration of depression and hypertension treatment: a pilot, randomized
      controlled trial.
AB  - PURPOSE: We wanted to examine whether integrating depression treatment into care
      for hypertension improved adherence to antidepressant and antihypertensive
      medications, depression outcomes, and blood pressure control among older primary
      care patients. METHODS: Older adults prescribed pharmacotherapy for depression
      and hypertension from physicians at a large primary care practice in West
      Philadelphia were randomly assigned to an integrated care intervention or usual
      care. Outcomes were assessed at baseline, 2, 4, and 6 weeks using the Center for
      Epidemiologic Studies Depression Scale (CES-D) to assess depression, an
      electronic monitor to measure blood pressure, and the Medication Event Monitoring
      System to assess adherence. RESULTS: In all, 64 participants aged 50 to 80 years
      participated. Participants in the integrated care intervention had fewer
      depressive symptoms (CES-D mean scores, intervention 9.9 vs usual care 19.3; P
      <.01), lower systolic blood pressure (intervention 127.3 mm Hg vs usual care
      141.3 mm Hg; P <.01), and lower diastolic blood pressure (intervention 75.8 mm Hg
      vs usual care 85.0 mm Hg; P <.01) compared with participants in the usual care
      group at 6 weeks. Compared with the usual care group, the proportion of
      participants in the intervention group who had 80% or greater adherence to an
      antidepressant medication (intervention 71.9% vs usual care 31.3%; P <.01) and to
      an antihypertensive medication (intervention 78.1% vs usual care 31.3%; P <.001)
      was greater at 6 weeks. CONCLUSION: A pilot, randomized controlled trial
      integrating depression and hypertension treatment was successful in improving
      patient outcomes. Integrated interventions may be more feasible and effective in
      real-world practices, where there are competing demands for limited resources.

PMID- 18626029
TI  - Self-rated cardiovascular risk and 15-year cardiovascular mortality.
AB  - PURPOSE: Many individuals perceive their cardiovascular disease (CVD) risk to be
      lower than established clinical tools would estimate, yet little is known about
      the long-term consequences of holding such optimistic beliefs. We evaluated
      whether lower self-ratings of CVD risk are associated with lower rates of CVD
      death after addressing potential confounding by an extensive set of social and
      biologic CVD risk factors. METHODS: We conducted a 15-year mortality surveillance
      study of adults aged 35 to 75 years from southeastern New England (n = 2,816) who
      had no history of myocardial infarction. Baseline evaluation in 1990-1992
      included household interview, anthropomorphic measures, and laboratory analyses.
      Outcomes were obtained using the National Death Index records through December
      2005. RESULTS: Rating oneself to be at lower-than-average risk for one's age and
      sex was associated with lower rates of CVD mortality among men (hazard ratio
      [HR]=0.3; 95% confidence interval [CI], 0.2-0.7) but not among women (HR = 0.9;
      95% CI, 0.5-1.7). None of the following weakened the findings among men:
      adjustment for baseline Framingham Risk Score, propensity score adjustment for
      both social and biologic factors, and censoring the first 2 years of
      surveillance. CONCLUSIONS: Lower self-ratings of CVD risk are independently
      associated with lower rates of CVD death among men.

PMID- 18626030
TI  - Healing in primary care: a vision shared by patients, physicians, nurses, and
      clinical staff.
AB  - PURPOSE: We wanted to understand the views of patients and clinicians on the
      central concept of healing and to identify major facilitators of and barriers to
      promoting healing in primary care. METHODS: We undertook a qualitative analysis
      of focus group discussions. Participants were drawn from primary care clinics of
      a large, integrated, health care system in Washington State in 2005. Nine focus
      groups included 84 participants: 28 patients, 23 primary care physicians (19
      family physicians), 20 registered nurses, 11 licensed practical nurses, and 2
      medical assistants. Randomly sampled established patients were aged from 21 to 65
      years; 71% were female. RESULTS: We found remarkable concordance across focus
      groups and among types of participants in the definition of healing: Healing is a
      dynamic process of recovering from a trauma or illness by working toward
      realistic goals, restoring function, and regaining a personal sense of balance
      and peace. Healing is a multidimensional process with physical, emotional, and
      spiritual dimensions. The key themes are as follows: (1) healing is
      multidimensional and holistic; (2) healing is a process, a journey; (3) the goal
      of healing is recovery or restoration; (4) healing requires the person to reach a
      place of personal balance and acceptance; and (5) relationships are essential to
      healing. Factors that facilitate healing help build relationships, improve
      communication, and share responsibility between the patient and clinician. Major
      barriers are logistical factors that limit high-quality time with healing
      professionals. CONCLUSIONS: Patients and health care team members share a vision
      of healing and agree on ways to enhance the process in primary care.

PMID- 18626031
TI  - Understanding healing relationships in primary care.
AB  - PURPOSE: Clinicians often have an intuitive understanding of how their
      relationships with patients foster healing. Yet we know little empirically about
      the experience of healing and how it occurs between clinicians and patients. Our
      purpose was to create a model that identifies how healing relationships are
      developed and maintained. METHODS: Primary care clinicians were purposefully
      selected as exemplar healers. Patients were selected by these clinicians as
      having experienced healing relationships. In-depth interviews, designed to elicit
      stories of healing relationships, were conducted with patients and clinicians
      separately. A multidisciplinary team analyzed the interviews using an iterative
      process, leading to the development of case studies for each clinician-patient
      dyad. A comparative analysis across dyads was conducted to identify common
      components of healing relationships RESULTS: Three key processes emerged as
      fostering healing relationships: (1) valuing/creating a nonjudgmental emotional
      bond; (2) appreciating power/consciously managing clinician power in ways that
      would most benefit the patient; and (3) abiding/displaying a commitment to caring
      for patients over time. Three relational outcomes result from these processes:
      trust, hope, and a sense of being known. Clinician competencies that facilitate
      these processes are self-confidence, emotional self-management, mindfulness, and
      knowledge. CONCLUSIONS: Healing relationships have an underlying structure and
      lead to important patient-centered outcomes. This conceptual model of clinician
      patient healing relationships may be generalizable to other kinds of healing
      relationships.

PMID- 18626032
TI  - Perceived accessibility as a predictor of youth smoking.
AB  - PURPOSE: Youths who smoke are more likely to perceive that cigarettes are easily
      accessible, but the relationship between perceived accessibility of cigarettes
      and the risk of smoking is not clear. The objective of this study was to
      determine whether perceived accessibility predicted future smoking among youths.
      METHODS: This study used data from the second Development and Assessment of
      Nicotine Dependence in Youth (DANDY-2) study, a 4-year (2002-2006) cohort study
      that began with 1,246 sixth-grade students in 6 Massachusetts communities. DANDY
      2 comprised 11 waves of in-person interviews. A total of 1,195 students who were
      aged 11 to 14 years at the baseline interview in 2002 were eligible for inclusion
      in this report. The outcomes for this study were the onset of smoking initiation
      and regular tobacco use. RESULTS: At baseline 1,027 students had never smoked
      cigarettes, and 168 had previously initiated smoking. During the 4 years of the
      study, 177 students newly initiated smoking, and 109 became regular smokers. In
      unadjusted city-stratified Cox proportional hazard models, perceived
      accessibility increased the risk for smoking initiation among nonsmokers and
      regular smoking among all participants in a dose-response fashion. Perceived
      accessibility also increased the risk for smoking progression among initiators in
      a dose-response fashion. The associations between perceived accessibility and
      smoking were robust to adjustment for peer and parental smoking. Youths with both
      perceived accessibility and peer-smokers had a higher risk of regular smoking and
      progression after initiation than either factor alone. These associations were
      stable to adjustment for potential confounders other than peer smoking.
      CONCLUSIONS: Perceived accessibility increases the risk for smoking among youths
      and has a stronger effect among those with peer smokers. There may be a role for
      identifying this group of youths for targeted interventions in child health care
      settings. Perceived accessibility should be carefully considered and measured in
      smoking intervention programs for teens.

PMID- 18626034
TI  - Using multiple sources of knowledge to reach clinical understanding of chronic
      fatigue syndrome.
AB  - PURPOSE: Chronic fatigue syndrome (CFS), or myalgic encephalitis (ME), is a
      contentious condition and often a diagnosis of exclusion. Current policy in the
      United Kingdom recommends management in primary care. We explored how patients
      with CFS/ME and family physicians understand this condition and how their
      understanding might affect the primary care consultation. METHODS: We undertook a
      qualitative study with patients and family physicians from North West England
      participating in a primary care-based randomized controlled trial (FINE Trial).
      Data were collected through purposive sampling and in-depth semistructured
      interviews with 24 patients and 14 family physicians. We analyzed interview
      transcripts using constant comparison methods. RESULTS: Family physicians access
      social and cultural knowledge to reach a clinical understanding of CFS/ME and its
      management. Patients recognize the difficulties family physicians encounter in
      understanding their symptoms and access similar nonclinical sources of
      information. We suggest that both patients and physicians use biomedical
      discourse within the consultation: the physician to maintain the position as an
      expert, the patient to engage the physician. CONCLUSIONS: Family physicians
      obtain information about CFS/ME from their nonprofessional world, which they
      incorporate into their professional realm. Patients and physicians describe the
      use of the discourse of science within consultations about CFS/ME. This form of
      shared understanding could lead to a positive collaborative interaction. Family
      physicians need a biomedical, evidence-based knowledge about CFS/ME. There is
      potential to use the rich knowledge base that patients can bring to consultations
      in training initiatives directed at family physicians.

PMID- 18626033
TI  - Evaluative criteria for qualitative research in health care: controversies and
      recommendations.
AB  - PURPOSE: We wanted to review and synthesize published criteria for good
      qualitative research and develop a cogent set of evaluative criteria. METHODS: We
      identified published journal articles discussing criteria for rigorous research
      using standard search strategies then examined reference sections of relevant
      journal articles to identify books and book chapters on this topic. A cross
      publication content analysis allowed us to identify criteria and understand the
      beliefs that shape them. RESULTS: Seven criteria for good qualitative research
      emerged: (1) carrying out ethical research; (2) importance of the research; (3)
      clarity and coherence of the research report; (4) use of appropriate and rigorous
      methods; (5) importance of reflexivity or attending to researcher bias; (6)
      importance of establishing validity or credibility; and (7) importance of
      verification or reliability. General agreement was observed across publications
      on the first 4 quality dimensions. On the last 3, important divergent
      perspectives were observed in how these criteria should be applied to qualitative
      research, with differences based on the paradigm embraced by the authors.
      CONCLUSION: Qualitative research is not a unified field. Most manuscript and
      grant reviewers are not qualitative experts and are likely to embrace a generic
      set of criteria rather than those relevant to the particular qualitative approach
      proposed or reported. Reviewers and researchers need to be aware of this tendency
      and educate health care researchers about the criteria appropriate for evaluating
      qualitative research from within the theoretical and methodological framework
      from which it emerges.

PMID- 18626035
TI  - Skin diseases in family medicine: prevalence and health care use.
AB  - PURPOSE: Ongoing care for patients with skin diseases can be optimized by
      understanding the incidence and population prevalence of various skin diseases
      and the patient-related factors related to the use of primary, specialty, and
      alternative health care for these conditions. We examined the recent prevalence
      of skin diseases in a defined population of family medicine patients, self
      reported disease-related quality of life, extent and duration of skin disease,
      and the use of health care by patients with skin diseases. METHODS: We undertook
      a morbidity registry-based epidemiological study to determine the prevalence of
      various skin diseases, using a patient questionnaire to inquire about health care
      use, within a network of family practices in the Netherlands with a practice
      population of approximately 12,000 citizens. RESULTS: Skin diseases accounted for
      12.4% of all diseases seen by the participating family physicians. Of the 857
      questionnaires sent to patients registered with a skin disease, 583 (68.0%) were
      returned, and 501 were suitable for analysis. In the previous year, 83.4% of the
      patients had contacted their family physician for their skin disease, 17.0% had
      contacted a medical specialist, and 5.2% had consulted an alternative health care
      practitioner. Overall, 65.1% contacted only their family physician. Patients who
      reported more severe disease and lower quality of life made more use of all forms
      of health care. CONCLUSION: This practice population-based study found that skin
      diseases account for 12.4% of diseases seen by family physicians, and that some
      skin problems may be seen more frequently. Although patients with more extensive
      skin diseases also obtain care from dermatologists, most patients have their skin
      diseases treated mainly by their family physician. Overall, patients with more
      severe disease and a lower quality of life seek more treatment.

PMID- 18626036
TI  - The development of an instrument for measuring healing.
AB  - PURPOSE: Our lack of ability to measure healing attributes impairs our ability to
      research the topic. The specific aim of this project is to describe the
      psychological and social construct of healing and to create a valid and reliable
      measurement scale for attributes of healing. METHODS: A content expert conducted
      a domain analysis examining the existing literature of midrange theories of
      healing. Theme saturation of content sampling was ensured by brainstorming more
      than 220 potential items. Selection of items was sequential: pile sorting and
      data reduction, with factor analysis of a mailed 54-item questionnaire. Criterion
      validity (convergent and divergent) and temporal reliability were established
      using a second mailing of the development version of the instrument. Construct
      validity was judged with structural equation modeling for goodness of fit.
      RESULTS: Cronbach's alpha of the original questionnaire was .869 and the final
      scale was .862. The test-retest reliability was .849. Eigenvalues for the 2
      factors were 8 and 4, respectively. Divergent and convergent validity using the
      Spann-Fischer Codependency Scale and SF-36 mental health and emotional subscales
      were consistent with predictions. The root mean square error of approximation was
      0.066 and Bentler's Comparative Fit Index was 0.871. Root mean square residual
      was 0.102. CONCLUSIONS: We developed a valid and reliable measurement scale for
      attributes of healing, which we named the Self-Integration Scale v 2.1. By
      creating a new variable, new areas of research in humanistic health care are
      possible.

PMID- 18626037
TI  - Community care of North Carolina: improving care through community health
      networks.
AB  - The United States leads the world in health care costs but ranks far below many
      developed countries in health outcomes. Finding ways to narrow this gap remains
      elusive. This article describes the response of one state to establish community
      health networks to achieve quality, utilization, and cost objectives for the care
      of its Medicaid recipients. The program, known as Community Care of North
      Carolina, is an innovative effort organized and operated by practicing community
      physicians. In partnership with hospitals, health departments, and departments of
      social services, these community networks have improved quality and reduced cost
      since their inception a decade ago. The program is now saving the State of North
      Carolina at least $160 million annually. A description of this experience and the
      lessons learned from it can inform others seeking to implement effective systems
      of care for patients with chronic illness.

PMID- 18626038
TI  - Dinosaurs, hospital ecosystems, and the future of family medicine.
AB  - The continued presence of the family physician within hospital systems is key to
      family medicine remaining an attractive, viable specialty in the ever-evolving
      world of medicine. One physician muses about her place in this complex ecosystem
      and believes that family physicians lose their voice and thus risk their own
      extinction when they opt out of hospital practice.

PMID- 18626039
TI  - National Institute for Program Director Development (NIPDD): a collaborative
      pursuit of excellence.

PMID- 18626040
TI  - Transformed's national demonstration project concludes.

PMID- 18626041
TI  - ABFM and MC-FP: second cohort on path to 3-year extension.

PMID- 18626043
TI  - Community faculty: caught between the dean's office, academic health centers,
      departments and the fiscal realities of primary care.

PMID- 18626044
TI  - Preventing blood clots after knee arthroscopy.

PMID- 18626045
TI  - High-normal blood pressure in young adults as a risk for atherosclerosis later in
      life.

PMID- 18626046
TI  - Low-molecular-weight heparin versus compression stockings for thromboprophylaxis
      after knee arthroscopy: a randomized trial.
AB  - BACKGROUND: Knee arthroscopy, the most common orthopedic operation worldwide,
      carries a definite risk for deep venous thrombosis; however, postsurgical
      thromboprophylaxis is not routinely recommended. OBJECTIVE: To evaluate whether
      low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and
      does not cause more complications than graduated compression stockings in adults
      having knee arthroscopy. DESIGN: Assessor-blind, randomized, controlled trial.
      SETTING: The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee
      surgery, random assignment, and bleeding event survey), and the Unit of
      Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation,
      follow-up, data management, and analysis), Italy. PATIENTS: 1761 consecutive
      patients undergoing knee arthroscopy between March 2002 and January 2006.
      INTERVENTION: Patients were randomly assigned to wear full-length graduated
      compression stocking for 7 days (660 patients) or to receive a once-daily
      subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657
      patients) or 14 days (444 patients). The data and safety monitoring board
      prematurely stopped the 14-day heparin group after the second interim analysis.
      MEASUREMENTS: Combined incidence of asymptomatic proximal deep venous thrombosis,
      symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end
      point) and combined incidence of major and clinically relevant bleeding events
      (primary safety end point). All patients had bilateral whole-leg ultrasonography
      at the end of the allocated prophylactic regimen or earlier if indicated. All
      patients with normal findings were followed for 3 months, and none was lost to
      follow-up. RESULTS: The 3-month cumulative incidence of asymptomatic proximal
      deep venous thrombosis, symptomatic venous thromboembolism, and all-cause
      mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657
      patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points
      [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients)
      in the prematurely stopped 14-day LMWH group. The cumulative incidence of major
      or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the
      stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute
      difference, -0.6 percentage point [CI, -1.5 to 0.2 percentage points]), and 0.5%
      (2 of 444 patients) in the 14-day LMWH group. LIMITATIONS: The study was not
      double-blind or double-dummy. Almost half of the events making up the composite
      outcome measure were distal deep venous thromboses. Stockings were used instead
      of placebo because of local prophylaxis policies. CONCLUSION: In patients
      undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end
      point of asymptomatic proximal deep venous thrombosis, symptomatic venous
      thromboembolism, and all-cause mortality more than did graduated compression
      stockings.

PMID- 18626047
TI  - Empirical fluconazole versus placebo for intensive care unit patients: a
      randomized trial.
AB  - BACKGROUND: Invasive infection with Candida species is an important cause of
      morbidity and mortality in intensive care unit (ICU) patients. Optimal preventive
      strategies have not been clearly defined. OBJECTIVE: To see whether empirical
      fluconazole improves clinical outcomes more than placebo in adult ICU patients at
      high risk for invasive candidiasis. DESIGN: Double-blind, placebo-controlled,
      randomized trial conducted from 1995 to 2000. SETTING: 26 ICUs in the United
      States. PATIENTS: 270 adult ICU patients with fever despite administration of
      broad-spectrum antibiotics. All had central venous catheters and an Acute
      Physiology and Chronic Health Evaluation II score greater than 16. INTERVENTION:
      Patients were randomly assigned to either intravenous fluconazole, 800 mg daily,
      or placebo for 2 weeks and were followed for 4 weeks thereafter. Two hundred
      forty-nine participants were available for outcome assessment. MEASUREMENTS: A
      composite primary outcome that defined success as all 4 of the following:
      resolution of fever; absence of invasive fungal infection; no discontinuation
      because of toxicity; and no need for a nonstudy, systemic antifungal medication
      (as assessed by a blinded oversight committee). RESULTS: Only 44 of 122 (36%)
      fluconazole recipients and 48 of 127 (38%) placebo recipients had a successful
      outcome (relative risk, 0.95 [95% CI, 0.69 to 1.32; P = 0.78]). The main reason
      for failure was lack of resolution of fever (51% for fluconazole and 57% for
      placebo). Documented invasive candidiasis occurred in 5% of fluconazole
      recipients and 9% of placebo recipients (relative risk, 0.57 [CI, 0.22 to 1.49]).
      Seven (5%) fluconazole recipients and 10 (7%) placebo recipients had adverse
      events resulting in discontinuation of the study drug. Discontinuation because of
      abnormal liver test results occurred in 3 (2%) fluconazole recipients and 5 (4%)
      placebo recipients. LIMITATIONS: Twenty-one randomly assigned patients were not
      included in the analysis because they either did not meet entry criteria or did
      not have postbaseline assessments. Fewer fungal infections than anticipated
      occurred in the control group. Confidence bounds were wide and did not exclude
      potentially important differences in outcomes between groups. CONCLUSION: In
      critically ill adults with risk factors for invasive candidiasis, empirical
      fluconazole did not clearly improve a composite outcome more than placebo.

PMID- 18626048
TI  - Prehypertension during young adulthood and coronary calcium later in life.
AB  - BACKGROUND: High blood pressure in middle age is a well-established risk factor
      for cardiovascular disease, but the consequences of low-level elevations during
      young adulthood are unknown. OBJECTIVE: To measure the association between
      prehypertension exposure before age 35 years and coronary calcium later in life.
      DESIGN: Prospective cohort study. SETTING: Four communities in the United States.
      PARTICIPANTS: Black and white men and women age 18 to 30 years recruited for the
      CARDIA (Coronary Artery Risk Development in Young Adults) Study in 1985 through
      1986 who were without hypertension before age 35 years. MEASUREMENTS: Blood
      pressure trajectories for each participant were estimated by using measurements
      from 7 examinations over the course of 20 years. Cumulative exposure to blood
      pressure in the prehypertension range (systolic blood pressure of 120 to 139 mm
      Hg, or diastolic blood pressure of 80 to 89 mm Hg) from age 20 to 35 years was
      calculated in units of mm Hg-years (similar to pack-years of tobacco exposure)
      and related to the presence of coronary calcium measured at each participant's
      last examination (mean age, 44 years [SD, 4]). RESULTS: Among 3560 participants,
      the 635 (18%) who developed prehypertension before age 35 years were more often
      black, male, overweight, and of lower socioeconomic status. Exposure to
      prehypertension before age 35 years, especially systolic prehypertension, showed
      a graded association with coronary calcium later in life (coronary calcium
      prevalence of 15%, 24%, and 38% for 0, 1 to 30, and >30 mm Hg-years of exposure,
      respectively; P < 0.001). This association remained strong after adjustment for
      blood pressure elevation after age 35 years and other coronary risk factors and
      participant characteristics. LIMITATION: Coronary calcium, although a strong
      predictor of future coronary heart disease, is not a clinical outcome.
      CONCLUSION: Prehypertension during young adulthood is common and is associated
      with coronary atherosclerosis 20 years later. Keeping systolic pressure below 120
      mm Hg before age 35 years may provide important health benefits later in life.

PMID- 18626049
TI  - Comparing patient-reported hospital adverse events with medical record review: do
      patients know something that hospitals do not?
AB  - BACKGROUND: Hospitals routinely survey patients about the quality of care they
      receive, but little is known about whether patient interviews can detect adverse
      events that medical record reviews do not. OBJECTIVE: To compare adverse events
      reported in postdischarge patient interviews with adverse events detected by
      medical record review. DESIGN: Random sample survey. SETTING: Massachusetts,
      2003. PATIENTS: Recently hospitalized adults. MEASUREMENTS: By using parallel
      methods, physicians reviewed postdischarge interviews and medical records to
      classify hospital adverse events. RESULTS: Among 998 study patients, 23% had at
      least 1 adverse event detected by an interview and 11% had at least 1 adverse
      event identified by record review. The kappa statistic showed relatively poor
      agreement between interviews and medical records for occurrence of any type of
      adverse event (kappa = 0.20 [95% CI, 0.03 to 0.27]) and somewhat better agreement
      between interviews and medical records for life-threatening or serious events
      (kappa = 0.33 [CI, 0.20 to 0.45]). Record review identified 11 serious,
      preventable events (1.1% of patients). Interviews identified an additional 21
      serious and preventable events that were not documented in the medical record,
      including 12 predischarge events and 9 postdischarge events, in which symptoms
      occurred after the patient left the hospital. LIMITATIONS: Patients had to be
      healthy enough to be interviewed. Delay in reaching patients (6 to 12 months
      after discharge) may have resulted in poor recall of events during the hospital
      stay. CONCLUSION: Patients report many events that are not documented in the
      medical record; some are serious and preventable. Hospitals should consider
      monitoring patient safety by adding questions about adverse events to
      postdischarge interviews.

PMID- 18626050
TI  - Meta-analysis: Combination endoscopic and drug therapy to prevent variceal
      rebleeding in cirrhosis.
AB  - BACKGROUND: Combining endoscopic therapy and beta-blockers may improve outcomes
      in patients with cirrhosis and bleeding esophageal varices. PURPOSE: To assess
      whether a combination of endoscopic and drug therapy prevents overall and
      variceal rebleeding and improves survival better than either therapy alone. DATA
      SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the
      Cochrane Database of Systematic Reviews, and conference proceedings through 30
      December 2007. STUDY SELECTION: Randomized trials comparing endoscopic plus beta
      blocker therapy with either therapy alone, without language restrictions. DATA
      EXTRACTION: Two reviewers independently extracted data on interventions and the
      primary study outcomes of overall rebleeding and mortality. Metaregression and
      stratified analysis were used to explore heterogeneity. DATA SYNTHESIS: 23 trials
      (1860 patients) met inclusion criteria. Combination therapy reduced overall
      rebleeding more than endoscopic therapy alone (pooled relative risk, 0.68 [95%
      CI, 0.52 to 0.89]; I(2) = 61%) or beta-blocker therapy alone (pooled relative
      risk, 0.71 [CI, 0.59 to 0.86]; I(2) = 0%). Combination therapy also reduced
      variceal rebleeding and variceal recurrence. Reduction in mortality from
      combination therapy did not statistically significantly differ from that from
      endoscopic (Peto odds ratio, 0.78 [CI, 0.58 to 1.07) or drug therapy (Peto odds
      ratio, 0.70 [CI, 0.46 to 1.06]). Effects were independent of the endoscopic
      procedure (injection sclerotherapy or banding). No trial-level variable
      associated with the effect was identified through metaregression or stratified
      analysis. LIMITATION: Statistically significant heterogeneity in trial quality
      and evidence for selective reporting and publication bias were found. CONCLUSION:
      A combination of endoscopic and drug therapy reduces overall and variceal
      rebleeding in cirrhosis more than either therapy alone.

PMID- 18626051
TI  - Initial drug resistance and tuberculosis treatment outcomes: systematic review
      and meta-analysis.
AB  - BACKGROUND: Despite the increasing prevalence of drug-resistant tuberculosis,
      most low- and middle-income countries use standardized regimens, without
      assessment of drug susceptibility. PURPOSE: To perform a systematic review and
      meta-analysis of the effect of initial drug resistance and treatment regimen on
      tuberculosis treatment outcomes. DATA SOURCES: PubMed, the Cochrane Central
      Database of Clinical Trials, and EMBASE were searched for studies published in
      English from 1965 to June 2007. Additional studies were identified from cited
      references. STUDY SELECTION: Randomized, controlled trials and cohort studies of
      standardized treatment of previously untreated patients with culture-confirmed
      pulmonary tuberculosis. Drug-susceptibility testing was done on pretreatment
      isolates from all patients and from patients with treatment failure or relapse.
      DATA EXTRACTION: Two authors reviewed the studies for methods, initial drug
      resistance, treatment regimens, and outcomes. DATA SYNTHESIS: Pooled cumulative
      incidences were computed with random-effects meta-analyses. Association between
      risk factors and outcomes were determined by using stratified analyses. The
      cumulative incidence of acquired drug resistance with initially pan-sensitive
      strains was 0.8% (95% CI, 0.5% to 1.0%) compared with 6% (CI, 4% to 8%) with
      initially single drug-resistant strains and 14% (CI, 9% to 20%) with initially
      polydrug-resistant strains. Failure and relapse were most strongly associated
      with initial drug resistance. Failure was also associated with shorter duration
      of rifampin therapy and nonuse of streptomycin, whereas the rate of relapse was
      higher with shorter duration of rifampin therapy and nonuse of pyrazinamide.
      LIMITATIONS: Few studies included HIV-infected persons, and treatment outcomes
      were pooled despite considerable heterogeneity. CONCLUSION: Treatment outcomes
      were substantially worse in the presence of initial drug resistance, which has
      important implications in resource-limited settings in which drug resistance is
      prevalent.

PMID- 18626052
TI  - The first use of penicillin in the United States.
AB  - The first use of penicillin in the United States occurred in 1942 and saved a
      moribund patient who had beta-hemolytic streptococcal sepsis. Some of the
      circumstances involved in obtaining and using the drug are described.

PMID- 18626053
TI  - Thromboprophylaxis in knee arthroscopy patients: revisiting values and
      preferences.

PMID- 18626054
TI  - The answer is in: fluconazole prophylaxis is not beneficial for intensive care
      unit patients without neutropenia.

PMID- 18626055
TI  - The content of their character.

PMID- 18626056
TI  - Drawing conclusions about short-term variability in liver function test results.

PMID- 18626057
TI  - Drawing conclusions about short-term variability in liver function test results.

PMID- 18626058
TI  - Drawing conclusions about short-term variability in liver function test results.

PMID- 18626059
TI  - Drawing conclusions about short-term variability in liver function test results.

PMID- 18626060
TI  - Not sold on performance measures.

PMID- 18626061
TI  - Oregon surpasses struggles of early reform and develops a road map for future
      success.

PMID- 18626062
TI  - Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology
      and pathology.
AB  - The membrane proteins CD38 and CD157 belong to an evolutionarily conserved family
      of enzymes that play crucial roles in human physiology. Expressed in distinct
      patterns in most tissues, CD38 (and CD157) cleaves NAD(+) and NADP(+), generating
      cyclic ADP ribose (cADPR), NAADP, and ADPR. These reaction products are essential
      for the regulation of intracellular Ca(2+), the most ancient and universal cell
      signaling system. The entire family of enzymes controls complex processes,
      including egg fertilization, cell activation and proliferation, muscle
      contraction, hormone secretion, and immune responses. Over the course of
      evolution, the molecules have developed the ability to interact laterally and
      frontally with other surface proteins and have acquired receptor-like features.
      As detailed in this review, the loss of CD38 function is associated with impaired
      immune responses, metabolic disturbances, and behavioral modifications in mice.
      CD38 is a powerful disease marker for human leukemias and myelomas, is directly
      involved in the pathogenesis and outcome of human immunodeficiency virus
      infection and chronic lymphocytic leukemia, and controls insulin release and the
      development of diabetes. Here, the data concerning diseases are examined in view
      of potential clinical applications in diagnosis, prognosis, and therapy. The
      concluding remarks try to frame all of the currently available information within
      a unified working model that takes into account both the enzymatic and
      receptorial functions of the molecules.

PMID- 18626064
TI  - Genesis and regulation of the heart automaticity.
AB  - The heart automaticity is a fundamental physiological function in higher
      organisms. The spontaneous activity is initiated by specialized populations of
      cardiac cells generating periodical electrical oscillations. The exact cascade of
      steps initiating the pacemaker cycle in automatic cells has not yet been entirely
      elucidated. Nevertheless, ion channels and intracellular Ca(2+) signaling are
      necessary for the proper setting of the pacemaker mechanism. Here, we review the
      current knowledge on the cellular mechanisms underlying the generation and
      regulation of cardiac automaticity. We discuss evidence on the functional role of
      different families of ion channels in cardiac pacemaking and review recent
      results obtained on genetically engineered mouse strains displaying dysfunction
      in heart automaticity. Beside ion channels, intracellular Ca(2+) release has been
      indicated as an important mechanism for promoting automaticity at rest as well as
      for acceleration of the heart rate under sympathetic nerve input. The potential
      links between the activity of ion channels and Ca(2+) release will be discussed
      with the aim to propose an integrated framework of the mechanism of automaticity.

PMID- 18626065
TI  - Activity-dependent structural and functional plasticity of astrocyte-neuron
      interactions.
AB  - Observations from different brain areas have established that the adult nervous
      system can undergo significant experience-related structural changes throughout
      life. Less familiar is the notion that morphological plasticity affects not only
      neurons but glial cells as well. Yet there is abundant evidence showing that
      astrocytes, the most numerous cells in the mammalian brain, are highly mobile.
      Under physiological conditions as different as reproduction, sensory stimulation,
      and learning, they display a remarkable structural plasticity, particularly
      conspicuous at the level of their lamellate distal processes that normally
      ensheath all portions of neurons. Distal astrocytic processes can undergo
      morphological changes in a matter of minutes, a remodeling that modifies the
      geometry and diffusion properties of the extracellular space and relationships
      with adjacent neuronal elements, especially synapses. Astrocytes respond to
      neuronal activity via ion channels, neurotransmitter receptors, and transporters
      on their processes; they transmit information via release of neuroactive
      substances. Where astrocytic processes are mobile then, astrocytic-neuronal
      interactions become highly dynamic, a plasticity that has important functional
      consequences since it modifies extracellular ionic homeostasis,
      neurotransmission, gliotransmission, and ultimately neuronal function at the
      cellular and system levels. Although a complete picture of intervening cellular
      mechanisms is lacking, some have been identified, notably certain permissive
      molecular factors common to systems capable of remodeling (cell surface and
      extracellular matrix adhesion molecules, cytoskeletal proteins) and molecules
      that appear specific to each system (neuropeptides, neurotransmitters, steroids,
      growth factors) that trigger or reverse the morphological changes.

PMID- 18626066
TI  - Regulation of coronary blood flow during exercise.
AB  - Exercise is the most important physiological stimulus for increased myocardial
      oxygen demand. The requirement of exercising muscle for increased blood flow
      necessitates an increase in cardiac output that results in increases in the three
      main determinants of myocardial oxygen demand: heart rate, myocardial
      contractility, and ventricular work. The approximately sixfold increase in oxygen
      demands of the left ventricle during heavy exercise is met principally by
      augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen
      extraction (which is already 70-80% at rest) increase only modestly in most
      species. In contrast, in the right ventricle, oxygen extraction is lower at rest
      and increases substantially during exercise, similar to skeletal muscle,
      suggesting fundamental differences in blood flow regulation between these two
      cardiac chambers. The increase in heart rate also increases the relative time
      spent in systole, thereby increasing the net extravascular compressive forces
      acting on the microvasculature within the wall of the left ventricle, in
      particular in its subendocardial layers. Hence, appropriate adjustment of
      coronary vascular resistance is critical for the cardiac response to exercise.
      Coronary resistance vessel tone results from the culmination of myriad
      vasodilator and vasoconstrictors influences, including neurohormones and
      endothelial and myocardial factors. Unraveling of the integrative mechanisms
      controlling coronary vasodilation in response to exercise has been difficult, in
      part due to the redundancies in coronary vasomotor control and differences
      between animal species. Exercise training is associated with adaptations in the
      coronary microvasculature including increased arteriolar densities and/or
      diameters, which provide a morphometric basis for the observed increase in peak
      coronary blood flow rates in exercise-trained animals. In larger animals trained
      by treadmill exercise, the formation of new capillaries maintains capillary
      density at a level commensurate with the degree of exercise-induced physiological
      myocardial hypertrophy. Nevertheless, training alters the distribution of
      coronary vascular resistance so that more capillaries are recruited, resulting in
      an increase in the permeability-surface area product without a change in
      capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the
      presence of lower circulating catecholamine levels appears to be due to increased
      receptor responsiveness to adrenergic stimulation. Exercise training also alters
      local control of coronary resistance vessels. Thus arterioles exhibit increased
      myogenic tone, likely due to a calcium-dependent protein kinase C signaling
      mediated alteration in voltage-gated calcium channel activity in response to
      stretch. Conversely, training augments endothelium-dependent vasodilation
      throughout the coronary microcirculation. This enhanced responsiveness appears to
      result principally from an increased expression of nitric oxide (NO) synthase.
      Finally, physical conditioning decreases extravascular compressive forces at rest
      and at comparable levels of exercise, mainly because of a decrease in heart rate.
      Impedance to coronary inflow due to an epicardial coronary artery stenosis
      results in marked redistribution of myocardial blood flow during exercise away
      from the subendocardium towards the subepicardium. However, in contrast to the
      traditional view that myocardial ischemia causes maximal microvascular dilation,
      more recent studies have shown that the coronary microvessels retain some degree
      of vasodilator reserve during exercise-induced ischemia and remain responsive to
      vasoconstrictor stimuli. These observations have required reassessment of the
      principal sites of resistance to blood flow in the microcirculation. A
      significant fraction of resistance is located in small arteries that are outside
      the metabolic control of the myocardium but are sensitive to shear and
      nitrovasodilators. The coronary collateral system embodies a dynamic network of
      interarterial vessels that can undergo both long- and short-term adjustments that
      can modulate blood flow to the dependent myocardium. Long-term adjustments
      including recruitment and growth of collateral vessels in response to arterial
      occlusion are time dependent and determine the maximum blood flow rates available
      to the collateral-dependent vascular bed during exercise. Rapid short-term
      adjustments result from active vasomotor activity of the collateral vessels.
      Mature coronary collateral vessels are responsive to vasodilators such as
      nitroglycerin and atrial natriuretic peptide, and to vasoconstrictors such as
      vasopressin, angiotensin II, and the platelet products serotonin and thromboxane
      A(2). During exercise, ss-adrenergic activity and endothelium-derived NO and
      prostanoids exert vasodilator influences on coronary collateral vessels.
      Importantly, alterations in collateral vasomotor tone, e.g., by exogenous
      vasopressin, inhibition of endogenous NO or prostanoid production, or increasing
      local adenosine production can modify collateral conductance, thereby influencing
      the blood supply to the dependent myocardium. In addition, vasomotor activity in
      the resistance vessels of the collateral perfused vascular bed can influence the
      volume and distribution of blood flow within the collateral zone. Finally, there
      is evidence that vasomotor control of resistance vessels in the normally perfused
      regions of collateralized hearts is altered, indicating that the vascular
      adaptations in hearts with a flow-limiting coronary obstruction occur at a global
      as well as a regional level. Exercise training does not stimulate growth of
      coronary collateral vessels in the normal heart. However, if exercise produces
      ischemia, which would be absent or minimal under resting conditions, there is
      evidence that collateral growth can be enhanced. In addition to ischemia, the
      pressure gradient between vascular beds, which is a determinant of the flow rate
      and therefore the shear stress on the collateral vessel endothelium, may also be
      important in stimulating growth of collateral vessels.

PMID- 18626063
TI  - LDL receptor-related protein 1: unique tissue-specific functions revealed by
      selective gene knockout studies.
AB  - The LDL receptor-related protein (originally called LRP, but now referred to as
      LRP1) is a large endocytic receptor that is widely expressed in several tissues.
      LRP1 is a member of the LDL receptor family that plays diverse roles in various
      biological processes including lipoprotein metabolism, degradation of proteases,
      activation of lysosomal enzymes, and cellular entry of bacterial toxins and
      viruses. Deletion of the LRP1 gene leads to lethality in mice, revealing a
      critical, but as of yet, undefined role in development. Tissue-specific gene
      deletion studies reveal an important contribution of LRP1 in the vasculature,
      central nervous system, macrophages, and adipocytes. Three important properties
      of LRP1 dictate its diverse role in physiology: 1) its ability to recognize more
      than 30 distinct ligands, 2) its ability to bind a large number of cytoplasmic
      adaptor proteins via determinants located on its cytoplasmic domain in a
      phosphorylation-specific manner, and 3) its ability to associate with and
      modulate the activity of other transmembrane receptors such as integrins and
      receptor tyrosine kinases.

PMID- 18626067
TI  - Intracellular transport and kinesin superfamily proteins, KIFs: structure,
      function, and dynamics.
AB  - Various molecular cell biology and molecular genetic approaches have indicated
      significant roles for kinesin superfamily proteins (KIFs) in intracellular
      transport and have shown that they are critical for cellular morphogenesis,
      functioning, and survival. KIFs not only transport various membrane organelles,
      protein complexes, and mRNAs for the maintenance of basic cellular activity, but
      also play significant roles for various mechanisms fundamental for life, such as
      brain wiring, higher brain functions such as memory and learning and activity
      dependent neuronal survival during brain development, and for the determination
      of important developmental processes such as left-right asymmetry formation and
      suppression of tumorigenesis. Accumulating data have revealed a molecular
      mechanism of cargo recognition involving scaffolding or adaptor protein
      complexes. Intramolecular folding and phosphorylation also regulate the binding
      activity of motor proteins. New techniques using molecular biophysics,
      cryoelectron microscopy, and X-ray crystallography have detected structural
      changes in motor proteins, synchronized with ATP hydrolysis cycles, leading to
      the development of independent models of monomer and dimer motors for processive
      movement along microtubules.

PMID- 18626068
TI  - Physiology and pathophysiology of potassium channels in gastrointestinal
      epithelia.
AB  - Epithelial cells of the gastrointestinal tract are an important barrier between
      the "milieu interne" and the luminal content of the gut. They perform transport
      of nutrients, salts, and water, which is essential for the maintenance of body
      homeostasis. In these epithelia, a variety of K(+) channels are expressed,
      allowing adaptation to different needs. This review provides an overview of the
      current literature that has led to a better understanding of the multifaceted
      function of gastrointestinal K(+) channels, thereby shedding light on
      pathophysiological implications of impaired channel function. For instance, in
      gastric mucosa, K(+) channel function is a prerequisite for acid secretion of
      parietal cells. In epithelial cells of small intestine, K(+) channels provide the
      driving force for electrogenic transport processes across the plasma membrane,
      and they are involved in cell volume regulation. Fine tuning of salt and water
      transport and of K(+) homeostasis occurs in colonic epithelia cells, where K(+)
      channels are involved in secretory and reabsorptive processes. Furthermore, there
      is growing evidence for changes in epithelial K(+) channel expression during cell
      proliferation, differentiation, apoptosis, and, under pathological conditions,
      carcinogenesis. In the future, integrative approaches using functional and
      postgenomic/proteomic techniques will help us to gain comprehensive insights into
      the role of K(+) channels of the gastrointestinal tract.

PMID- 18626069
TI  - Histamine in the nervous system.
AB  - Histamine is a transmitter in the nervous system and a signaling molecule in the
      gut, the skin, and the immune system. Histaminergic neurons in mammalian brain
      are located exclusively in the tuberomamillary nucleus of the posterior
      hypothalamus and send their axons all over the central nervous system. Active
      solely during waking, they maintain wakefulness and attention. Three of the four
      known histamine receptors and binding to glutamate NMDA receptors serve multiple
      functions in the brain, particularly control of excitability and plasticity. H1
      and H2 receptor-mediated actions are mostly excitatory; H3 receptors act as
      inhibitory auto- and heteroreceptors. Mutual interactions with other transmitter
      systems form a network that links basic homeostatic and higher brain functions,
      including sleep-wake regulation, circadian and feeding rhythms, immunity,
      learning, and memory in health and disease.

PMID- 18626070
TI  - New developments on gill innervation: insights from a model vertebrate.
AB  - The fish gill is a highly specialized and complex organ that performs a variety
      of important physiological functions. In this article, we briefly review the
      innervation of important structures of the branchial region, such as the gill
      filaments, respiratory lamellae and pseudobranch, and discuss the physiological
      significance of this innervation within the context of homeostatic functions of
      the gill, such as oxygen sensing and ion regulation. Studies in zebrafish
      utilizing techniques of confocal microscopy and immunolabelling, with specific
      antibodies against neuronal markers, have recently led to the characterization of
      innervation patterns in the gills not attained with traditional techniques of
      histochemistry and electron microscopy. We will discuss the association of
      putative sensory nerve fibres with O2-chemoreceptive neuroepithelial cells and
      the implications of dual sensory pathways for cardiorespiratory and vascular
      control. In addition, the idea of the neural control of ion regulation in the
      gill based on the apparent innervation of mitochondria-rich cells, and the role
      of innervation in the pseudobranch, will be presented.

PMID- 18626071
TI  - Sexual dimorphism in auditory mechanics: tympanal vibrations of Cicada orni.
AB  - In cicadas, the tympanum is anatomically intricate and employs complex vibrations
      as a mechanism for auditory frequency analysis. Using microscanning laser Doppler
      vibrometry, the tympanal mechanics of Cicada orni can be characterized in
      controlled acoustical conditions. The tympanum of C. orni moves following a
      simple drum-like motion, rather than the travelling wave found in a previous
      study of Cicadatra atra. There is a clear sexual dimorphism in the tympanal
      mechanics. The large male tympanum is unexpectedly insensitive to the dominant
      frequency of its own calling song, possibly a reflection of its dual purpose as a
      sound emitter and receiver. The small female tympanum appears to be mechanically
      sensitive to the dominant frequency of the male calling song and to high
      frequency sound, a capacity never suspected before in these insects. This sexual
      dimorphism probably results from a set of selective pressures acting in divergent
      directions, which are linked to the different role of the sexes in sound
      reception and production. These discoveries serve to indicate that there is far
      more to be learnt about the development of the cicada ear, its biomechanics and
      evolution, and the cicada's acoustic behaviour.

PMID- 18626072
TI  - Nitric oxide induces aspects of egg-laying behavior in Aplysia.
AB  - Aplysia egg laying is a complex behavior requiring synchronized activity in many
      organs. Aspects of the behavior are synchronized via the direct effects of
      peptide bag cell neurohormones and via stimuli arising during the behavior.
      Stimuli synchronizing egg laying were examined by treating A. fasciata with a
      nitric oxide (NO) donor. NO elicited normal appetitive and consummatory behaviors
      leading to the deposition of cordons containing egg capsules without eggs. The
      sites at which NO acts were investigated. The latency to egg deposition in
      response to a NO donor was shorter than that in response to other stimuli,
      consistent with NO acting at downstream sites from those affected by the other
      stimuli. The NO donor does not act on neurons in the head ganglia presynaptic to
      the bag cells or on the bag cells. Ligating the small hermaphroditic duct
      connecting the gonad to the accessory genital mass blocked egg laying in response
      to bag cell homogenates, but not in response to exogenous NO, indicating that NO
      does not act on the gonad. NO is released by transport of eggs along the small
      hermaphroditic duct, and NO directly acts on the accessory genital mass which
      packages eggs. NO also acts at a second site, independent of the effect on the
      accessory genital mass. A NO donor activates appetitive behaviors that normally
      precede egg laying even in A. californica that are unable to lay eggs.

PMID- 18626073
TI  - In vivo strains in the femur of river cooter turtles (Pseudemys concinna) during
      terrestrial locomotion: tests of force-platform models of loading mechanics.
AB  - Previous analyses of ground reaction force (GRF) and kinematic data from river
      cooter turtles (Pseudemys concinna) during terrestrial walking led to three
      primary conclusions about the mechanics of limb bone loading in this lineage: (1)
      the femur was loaded in a combination of axial compression, bending and torsion,
      similar to previously studied non-avian reptiles, (2) femoral shear stresses were
      high despite the possession of a reduced tail in turtles that does not drag on
      the ground and (3) stress-based calculations of femoral safety factors indicated
      high values in bending and torsion, similar to other reptiles and suggesting that
      substantial 'overbuilding' of limb bones could be an ancestral feature of
      tetrapods. Because force-platform analyses produce indirect estimates of bone
      loading, we sought to validate these conclusions by surgically implanting strain
      gauges on turtle femora to directly measure in vivo strains during terrestrial
      walking. Strain analyses verified axial compression and bending as well as high
      torsion in turtle femora, with peak axial strains comparable to those of other
      non-avian reptiles at similar walking speeds but higher peak shear strains
      approaching 2000 microepsilon. Planar strain analyses showed patterns of neutral
      axis (NA) of femoral bending orientations and shifting generally consistent with
      our previous force-platform analyses of bone stresses, tending to place the
      anterior and dorsal aspects of the femur in tension and verifying an unexpected
      pattern from our force studies that differs from patterns in other non-avian
      reptiles. Calculated femoral safety factors were 3.8 in torsion and ranged from
      4.4 to 6.9 in bending. Although these safety factors in bending were lower than
      values derived from our stress-based calculations, they are similar to strain
      based safety factors calculated for other non-avian reptiles in terrestrial
      locomotion and are still high compared with safety factors calculated for limb
      bones of birds and mammals. These findings are consistent with conclusions drawn
      from our previous models of limb bone stresses in turtles and suggest that not
      only are turtle limb bones 'overbuilt' in terms of resisting the loads that they
      experience during locomotion but also, across tetrapod lineages, elevated torsion
      and high limb bone safety factors may be primitive features of limb bone design.

PMID- 18626074
TI  - Differences in the sleep architecture of forager and young honeybees (Apis
      mellifera).
AB  - Honeybee (Apis mellifera) foragers are among the first invertebrates for which
      sleep behavior has been described. Foragers (typically older than 21 days) have
      strong circadian rhythms; they are active during the day, and sleep during the
      night. We explored whether young bees (approximately 3 days of age), which are
      typically active around-the-clock with no circadian rhythms, also exhibit sleep
      behavior. We combined 24-hour video recordings, detailed behavioral observations,
      and analyses of response thresholds to a light pulse for individually housed bees
      in various arousal states. We characterized three sleep stages in foragers on the
      basis of differences in body posture, bout duration, antennae movements and
      response threshold. Young bees exhibited sleep behavior consisting of the same
      three stages as observed in foragers. Sleep was interrupted by brief awakenings,
      which were as frequent in young bees as in foragers. Beyond these similarities,
      we found differences in the sleep architecture of young bees and foragers. Young
      bees passed more frequently between the three sleep stages, and stayed longer in
      the lightest sleep stage than foragers. These differences in sleep architecture
      may represent developmental and/or environmentally induced variations in the
      neuronal network underlying sleep in honeybees. To the best of our knowledge,
      this is the first evidence for plasticity in sleep behavior in insects.

PMID- 18626075
TI  - The elusive crypt olfactory receptor neuron: evidence for its stimulation by
      amino acids and cAMP pathway agonists.
AB  - Crypt olfactory receptor neurons (ORNs) are a third type of chemosensory neuron
      along with ciliated and microvillous ORNs in the olfactory epithelium of fishes,
      but their functional role is still unknown. To investigate their odorant response
      properties and possible transduction pathways, we recorded crypt ORN activity
      with calcium imaging and the patch clamp technique in its cell-attached mode in
      combination with odorant and agonist stimulation. Bile salts and putative fish
      pheromones did not elicit responses with either method, but the cells frequently
      responded to amino acids, with excitation and intracellular calcium signals. 8Br
      cAMP and IBMX plus forskolin stimulated over 40% of crypt ORNs and triggered
      calcium signals in a similar percentage. Furthermore, crypt ORNs were
      immunoreactive to an antiserum against adenylate cyclase III. Together, these
      data suggest the presence of a cAMP transduction pathway, which might transduce
      odorants such as amino acids.

PMID- 18626076
TI  - Quantifying avian sexual dichromatism: a comparison of methods.
AB  - Recent advances in portable spectrophotometers have allowed researchers to
      collect quantitative, objective data on colour. There are few comparisons of the
      different methods used to summarize and analyse spectrophotometer data, however.
      Using colour data on over 900 species of birds, we compared three methods of
      calculating sexual dichromatism using spectrophotometer data. We also compared
      sexual dichromatism calculated from spectrophotometer data, in both the
      ultraviolet (UV) and bird-visible range, with human estimates of sexual
      dichromatism. We found that all three methods, principal component analysis,
      segment classification and colour discriminability, yielded essentially
      comparable estimates of dichromatism for our extensive sample of birds. Certain
      methods may be better suited to a particular study depending on the questions
      addressed and the specific colours examined. We found that human visual estimates
      of dichromatism were similar to spectrophotometer estimates of dichromatism in
      the bird-visible range; however, human visual estimates did not predict the
      extent of UV dichromatism. Therefore, the conclusions of previous studies that
      relied on human vision to assess sexual dichromatism should be reliable. It is
      not possible, however, to predict a priori whether a species exhibits UV
      dichromatism without spectrophotometer measurements.

PMID- 18626077
TI  - The neuroethology of song cessation in response to gleaning bat calls in two
      species of katydids, Neoconocephalus ensiger and Amblycorypha oblongifolia.
AB  - We investigated whether the use of primary or secondary behavioural defences is
      related to prey sensory thresholds using two species of North American katydids,
      Neoconocephalus ensiger and Amblycorypha oblongifolia. Male katydids produce
      intense calling songs to attract mates, and many gleaning bat species are known
      to use these calls to locate them as prey. Low duty cycle calling (i.e. sporadic
      calls) is a primary defence against gleaning bats (prevents attacks), and song
      cessation is a secondary defence (enables survival of an attack), for which these
      two species show behavioural differences. Echolocation calls of Myotis
      septentrionalis, a sympatric gleaning bat species, were broadcast to singing
      katydids and to neural preparations of these katydids to test if differences in
      behavioural response were related to differences in auditory sensitivity. We
      measured thresholds and firing patterns of the T-cell, an auditory interneuron
      involved in predator detection. We hypothesized that low duty cycle calling is
      the best defence for species not sensitive enough to mount a secondary defence in
      response to predator cues; therefore, we predicted that N. ensiger (high duty
      cycle song) would have lower behavioural and T-cell thresholds than A.
      oblongifolia (low duty cycle song). Although more N. ensiger ceased singing than
      A. oblongifolia, the number and maximum firing rate of T-cell action potentials
      did not differ between species for echolocation call sequences. We suggest that
      the T-cell has divergent functions within the Tettigoniidae, including predator
      and mate detection, and the function could be context dependent in some species.

PMID- 18626078
TI  - Caste differences in venom volatiles and their effect on alarm behaviour in the
      paper wasp Polistes dominulus (Christ).
AB  - Foundresses and workers of Polistes paper wasps show slight morphological and
      physiological differences. However, after the emergence of the workers, the
      castes can be readily discriminated by their behaviour: the dominant foundress is
      the principal egg-layer, whereas workers perform different tasks linked to colony
      development. Previous studies have demonstrated in this genus that defence of the
      colony by the workers is more effectively carried out by a collective response
      elicited by venom volatiles used as alarm pheromones. In the present study, gas
      chromatography-mass spectrometry analyses of the venom volatiles of foundresses
      and workers of Polistes dominulus (Christ) show predominantly quantitative
      differences. Spiroacetals, mainly (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane,
      are significantly higher in the venom volatiles fraction of workers, whereas the
      amount of N-(3-methylbutyl)acetamide is almost double in foundresses. On the
      basis of the chemical results, behavioural assays were performed on fifteen field
      colonies to test the alarm response of the resident wasps to venom extracts from
      foundresses and workers. Our behavioural results suggest that worker venom has a
      stronger alarm effect on the colonies than that of the foundresses, which seems
      unable to elicit the complete alarm response ending with a final attack and
      sting. The venom volatiles of P. dominulus workers serve mainly to alarm the
      colony whilst those of foundresses may also be linked to additional functions
      related to conspecific interactions.

PMID- 18626079
TI  - Physiological and molecular mechanisms of osmoregulatory plasticity in killifish
      after seawater transfer.
AB  - We have explored the molecular and physiological responses of the euryhaline
      killifish Fundulus heteroclitus to transfer from brackish water (10% seawater) to
      100% seawater for 12 h, 3 days or 7 days. Plasma [Na+] and [Cl-] were unchanged
      after transfer, and plasma cortisol underwent a transient increase. Na+/K+-ATPase
      activity increased 1.5-fold in the gills and opercular epithelium at 7 days
      (significant in gills only), responses that were preceded by three- to fourfold
      increases in Na+/K+-ATPase alpha(1a) mRNA expression. Expression of Na+/K+/2Cl-
      cotransporter 1, cystic fibrosis transmembrane conductance regulator (CFTR) Cl-
      channel, Na+/H+-exchanger 3 (significant in opercular epithelium only) and
      carbonic anhydrase II mRNA also increased two- to fourfold after transfer.
      Drinking rate increased over twofold after 12 h and remained elevated for at
      least 7 days. Surprisingly, net rates of water and ion absorption measured in
      vitro across isolated intestines decreased approximately 50%, possibly due to
      reduced salt demands from the diet in seawater, but water absorption capacity
      still exceeded the drinking rate. Changes in bulk water absorption were well
      correlated with net ion absorption, and indicated that slightly hyperosmotic
      solutions (>or=298 mmol l(-1)) were transported. There were no reductions in
      unidirectional influx of Na+ from luminal to serosal fluid or intestinal Na+/K+
      ATPase activity after transfer. Overall, our results indicate that gill and
      opercular epithelia function similarly at a molecular level in seawater, in
      contrast to their divergent function in freshwater, and reveal unexpected changes
      in intestinal function. As such they provide further insight into the mechanisms
      of euryhalinity in killifish.

PMID- 18626080
TI  - In vivo regulation of rainbow trout lipolysis by catecholamines.
AB  - Lipolysis provides fatty acids that support key life processes by functioning as
      membrane components, oxidative fuels and metabolic signals. It is commonly
      measured as the rate of appearance of glycerol (Ra glycerol). Its in vivo
      regulation by catecholamines has been thoroughly investigated in mammals, but
      little information is available for ectotherms. Therefore, the goals of this
      study were, first, to characterize the effects of the catecholamines
      norepinephrine (NE) and epinephrine (Epi) on the lipolytic rate of intact rainbow
      trout (Oncorhynchus mykiss) and, second, to determine whether the plasma glycerol
      concentration is a reliable index of Ra glycerol. Our results show that baseline
      Ra glycerol (4.6+/-0.4 micromol kg(-1) min(-1)) is inhibited by NE (-56%),
      instead of being stimulated, as in mammals, whereas Epi has the same activating
      effect in both groups of vertebrates (+167%). NE-induced inhibition of fish
      lipolysis might play a particularly important role during aquatic hypoxia, when
      survival often depends on regulated metabolic depression. The plasma glycerol
      concentration is a poor predictor of Ra glycerol, and it should not be used as an
      index of lipolysis. Trout maintain a particularly high baseline lipolytic rate
      because only 13% of the fatty acids provided are sufficient to support total
      energy expenditure, whereas the remaining fatty acids must undergo
      reesterification (87%).

PMID- 18626081
TI  - Branchial expression and localization of SLC9A2 and SLC9A3 sodium/hydrogen
      exchangers and their possible role in acid-base regulation in freshwater rainbow
      trout (Oncorhynchus mykiss).
AB  - Experiments were conducted on adult rainbow trout (Oncorhynchus mykiss) to test
      the hypothesis that SLC9 Na+/H+ exchangers (SLC9A2, NHE2; and SLC9A3, NHE3) on
      the gill epithelium are localized specifically to a subset of mitochondria-rich
      cells (MRCs) that are unable to bind peanut lectin agglutinin (PNA). This cell
      type, termed the PNA- MRC, is a sub-type of MRC believed to function in Na+
      uptake and acid excretion. A technique using biotinylated PNA was used to
      distinguish between the PNA- and PNA+ MRCs on fixed gill sections. In contrast to
      expectations, both NHE2 (mRNA) and NHE3 (protein) were confined to cells enriched
      with Na+/K+-ATPase and capable of binding PNA. Thus, in trout, NHE2 and NHE3 are
      localized to PNA+ MRCs, the cells previously believed to be responsible for Cl-
      uptake and base excretion. Levels of mRNA for NHE2, the predominant isoform in
      the gill, were increased during 72 h of hypercapnic acidosis; NHE3 mRNA and
      protein levels were unaffected. Because plasma cortisol levels were increased
      during hypercapnia (from 35.3+/-9.4 to 100.1+/-30.9 ng ml(-1)), the effects of
      experimentally elevated cortisol levels on NHE expression were investigated. The
      elevation of plasma cortisol using intraperitoneal implants caused a significant
      increase in NHE2 mRNA expression without affecting NHE3 mRNA or protein
      abundance. Thus, we suggest that NHE2 contributes to acid-base regulation during
      hypercapnia owing to its transcriptional regulation by cortisol. The finding of
      NHE expression in PNA+ MRCs is discussed with reference to current models of
      ionic and acid-base regulation in teleost fish.

PMID- 18626082
TI  - Context-dependent olfactory enhancement of optomotor flight control in
      Drosophila.
AB  - Sensing and following the chemical plume of food odors is a fundamental challenge
      faced by many organisms. For flying insects, the task is complicated by wind that
      distorts the plume and buffets the fly. To maintain an upwind heading, and thus
      stabilize their orientation in a plume, insects such as flies and moths make use
      of strong context-specific visual equilibrium reflexes. For example, flying
      straight requires the regulation of image rotation across the eye, whereas
      minimizing side-slip and avoiding a collision require regulation of image
      expansion. In flies, visual rotation stabilizes plume tracking, but rotation and
      expansion optomotor responses are controlled by separate visual pathways. Are
      olfactory signals integrated with optomotor responses in a manner dependent upon
      visual context? We addressed this question by investigating the effect of an
      attractive food odor on active optomotor flight control. Odorant caused flies
      both to increase aerodynamic power output and to steer straighter. However, when
      challenged with wide-field optic flow, odor resulted in enhanced amplitude
      rotation responses but reduced amplitude expansion responses. For both visual
      conditions, flies tracked motion signals more closely in odor, an indication of
      increased saliency. These results suggest a simple search algorithm by which
      olfactory signals improve the salience of visual stimuli and modify optomotor
      control in a context-dependent manner, thereby enabling an animal to fly straight
      up a plume and approach odiferous objects.

PMID- 18626083
TI  - The role of the antennae during courtship behaviour in the parasitic wasp
      Trichopria drosophilae.
AB  - We have studied the courtship behaviour of Trichopria drosophilae Perkins
      (Hymenoptera: Diapriidae), a pupal parasitoid of the common fruit fly Drosophila
      melanogaster Meigen (Diptera: Drosophilidae), to understand the role of the
      antennae. Virgin pairs of the parasitoid perform an intense and stereotyped
      antennal courtship, which leads to copulation. During antennation, the two male
      fourth antennomeres come into contact with the two apical female antennomeres,
      and thus the secretion produced by the sex pheromone gland is spread onto the
      female receptors. By preventing the transfer of the courtship pheromone from male
      to female antennae, mating was inhibited. Moreover, selective ablation of single
      antennae demonstrated that the courtship pheromone acts on contact. When antennae
      of both sexes were partially removed (ablation at the same side, i.e. right or
      left) courtship was successful and copulation occurred. In contrast, in the case
      of antennal ablation at opposite sides, courtship failed despite the short
      distance between secretion and receptors. These results confirm the hypothesis
      that T. drosophilae male antennal glands are the release site of a contact
      courtship pheromone, playing a key role in mating behaviour. The occurrence of
      male antennal glands in Hymenoptera and other insect orders is discussed.

PMID- 18626085
TI  - Long-term changes in the chlorophyll fluorescence of bleached and recovering
      corals from Hawaii.
AB  - Chlorophyll fluorescence has been used to predict and monitor coral bleaching
      over short timescales (hours to days), but long-term changes during recovery
      remain largely unknown. To evaluate changes in fluorescence during long-term
      bleaching and recovery, Porites compressa and Montipora capitata corals were
      experimentally bleached in tanks at 30 degrees C for 1 month, while control
      fragments were maintained at 27 degrees C. A pulse amplitude modulated
      fluorometer measured the quantum yield of photosystem II fluorescence (Fv/Fm) of
      the zooxanthellae each week during bleaching, and after 0, 1.5, 4 and 8 months
      recovery. M. capitata appeared bleached 6 days sooner than P. compressa, yet
      their fluorescence patterns during bleaching did not significantly differ.
      Changes in minimum (Fo), maximum (Fm) and variable (Fv) fluorescence throughout
      bleaching and recovery indicated periods of initial photoprotection followed by
      photodamage in both species, with P. compressa requiring less time for
      photosystem II (PS II) repair than M. capitata. Fv/Fm fully recovered 6.5 months
      earlier in P. compressa than M. capitata, suggesting that the zooxanthellae of P.
      compressa were more resilient to bleaching stress.

PMID- 18626084
TI  - Size- and age-dependent changes in adductor muscle swimming physiology of the
      scallop Aequipecten opercularis.
AB  - The decline of cellular and especially mitochondrial functions with age is, among
      other causes, held responsible for a decrease in physiological fitness and
      exercise capacity during lifetime. We investigated size- and age-related changes
      in the physiology of exercising specimens of the short lived swimming scallop
      Aequipecten opercularis (maximum life span 8 to 10 years) from the Isle of Man,
      UK. A. opercularis swim mainly to avoid predators, and a decrease in swimming
      abilities would increase the risk of capture and lower the rates of survival.
      Bigger (older) individuals were found to have lower mitochondrial volume density
      and aerobic capacities (citrate synthase activity and adenylates) as well as less
      anaerobic capacity deduced from the amount of glycogen stored in muscle tissue.
      Changes in redox potential, tissue pH and the loss of glutathione in the swimming
      muscle during the exercise were more pronounced in young compared to older
      individuals. This indicates that older individuals can more effectively stabilize
      cellular homeostasis during repeated exercise than younger animals but with a
      possible fitness cost as the change in physiology with age and size might result
      in a changed escape response behaviour towards predators.

PMID- 18626086
TI  - Insulin regulates the expression of several metabolism-related genes in the liver
      and primary hepatocytes of rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout have a limited ability to use dietary carbohydrates efficiently and
      are considered to be glucose intolerant. Administration of carbohydrates results
      in persistent hyperglycemia and impairs post-prandial down regulation of
      gluconeogenesis despite normal insulin secretion. Since gluconeogenic genes are
      mainly under insulin control, we put forward the hypothesis that the
      transcriptional function of insulin as a whole may be impaired in the trout
      liver. In order to test this hypothesis, we performed intraperitoneal
      administration of bovine insulin to fasted rainbow trout and also subjected
      rainbow trout primary hepatocytes to insulin and/or glucose stimulation. We
      demonstrate that insulin was able to activate Akt, a key element in the insulin
      signaling pathway, and to regulate hepatic metabolism-related target genes both
      in vivo and in vitro. In the same way as in mammals, insulin decreased mRNA
      expression of gluconeogenic genes, including glucose 6-phosphatase (G6Pase),
      fructose 1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase
      (PEPCK). Insulin also limited the expression of carnitine palmitoyltransferase 1
      (CPT1), a limiting enzyme of fatty acid beta-oxidation. In vitro studies revealed
      that, as in mammals, glucose is an important regulator of some insulin target
      genes such as the glycolytic enzyme pyruvate kinase (PK) and the lipogenic enzyme
      fatty acid synthase (FAS). Interestingly, glucose also stimulates expression of
      glucokinase (GK), which has no equivalent in mammals. This study demonstrates
      that insulin possesses the intrinsic ability to regulate hepatic gene expression
      in rainbow trout, suggesting that other hormonal or metabolic factors may
      counteract some of the post-prandial actions of insulin.

PMID- 18626087
TI  - Experimental reduction of ultraviolet wavelengths reflected from parasitic eggs
      affects rejection behaviour in the blackcap Sylvia atricapilla.
AB  - Hosts of brood parasites use a variety of cues relating to eggshell appearance of
      parasitic eggs, which facilitate their recognition and rejection. It has been
      documented that host visual perception of different colours including UV
      wavelengths plays an important role in this respect. In the study reported here,
      we aimed to test whether artificial reduction of the UV wavelengths reflected
      from parasitic eggshell affects rejection behaviour in the blackcap Sylvia
      atricapilla. To achieve this goal, we experimentally manipulated, with UV, part
      of spectra reflected from conspecific eggs and reduced it into the range of 320
      350 nm. We used an ultraviolet light blocker, which did not influence the
      reflectance shape of other spectrum parts. We also used a group of experimental
      eggs coated in Vaseline, which had no effect on the spectral shape in the UV or
      visible ranges of the light spectrum. Additionally, we used a third experimental
      group of unmanipulated eggs as a control. The experimental eggs coated in the UV
      blocker were rejected at a higher rate than those coated in the Vaseline.
      Moreover, a binary logistic regression revealed that an artificial reduction of
      the UV wavelengths reflected from the parasitic egg significantly affected the
      probability of being rejected by the hosts. To our knowledge, this is the first
      experimental study to reveal that manipulation with UV wavelengths affects the
      recognition of parasitic eggs, indicating that the UV part of the spectrum has an
      important role in host recognition behaviour.

PMID- 18626088
TI  - Differential roles of p38-MAPK and JNKs in mediating early protection or
      apoptosis in the hyperthermic perfused amphibian heart.
AB  - In the present study the activation of p38 mitogen-activated protein kinase (p38
      MAPK) and c-Jun N-terminal kinases (JNKs) by hyperthermia was investigated in the
      isolated perfused Rana ridibunda heart. Hyperthermia (42 degrees C) was found to
      profoundly stimulate p38-MAPK phosphorylation within 0.5 h, with maximal values
      being attained at 1 h [4.503(+/-0.577)-fold relative to control, P<0.01]. JNKs
      were also activated under these conditions in a sustained manner for at least 4 h
      [2.641(+/-0.217)-fold relative to control, P<0.01]. Regarding their substrates,
      heat shock protein 27 (Hsp27) was maximally phosphorylated at 1 h [2.261(+/
      0.327)-fold relative to control, P<0.01] and c-Jun at a later phase [3 h:
      5.367(+/-0.081)-fold relative to control, P<0.001]. Hyperthermia-induced p38-MAPK
      activation was found to be dependent on the Na+/H+ exchanger 1 (NHE1) and was
      also suppressed by catalase (Cat) and superoxide dismutase (SOD), implicating the
      generation of reactive oxygen species (ROS). ROS were also implicated in the
      activation of JNKs by hyperthermia, with the Na+/K+-ATPase acting as a mediator
      of this effect at an early stage and the NHE1 getting involved at a later time
      point. Finally, JNKs were found to be the principal mediators of the apoptosis
      induced under hyperthermic conditions, as their inhibition abolished poly(ADP
      ribose) polymerase (PARP) cleavage after 4 h at 42 degrees C. Overall, to our
      knowledge, this study highlights for the first time the variable mediators
      implicated in the transduction of the hyperthermic signal in the isolated
      perfused heart of an ectotherm and deciphers a potential salutary effect of p38
      MAPK as well as the fundamental role of JNKs in the induced apoptosis.

PMID- 18626089
TI  - The alkaline tide and ammonia excretion after voluntary feeding in freshwater
      rainbow trout.
AB  - We investigated the potential acid-base and nitrogenous waste excretion
      challenges created by voluntary feeding in freshwater rainbow trout, with
      particular focus on the possible occurrence of an alkaline tide (a metabolic
      alkalosis created by gastric HCl secretion during digestion). Plasma metabolites
      (glucose, urea and ammonia) were measured at various time points before and after
      voluntary feeding to satiation (approximately 5% body mass meal of dry commercial
      pellets), as was the net flux of ammonia and titratable alkalinity to the water
      from unfed and fed fish. Arterial blood, sampled by indwelling catheter, was
      examined for post-prandial effects on pH, plasma bicarbonate and plasma CO2
      tension. There was no significant change in plasma glucose or urea concentrations
      following feeding, whereas plasma ammonia transiently increased, peaking at
      threefold above resting values at 12 h after the meal and remaining elevated for
      24 h. The increased plasma ammonia was correlated with an increase in net ammonia
      excretion to the water, with fed fish significantly elevating their net ammonia
      excretion two- to threefold between 12 and 48 h post feeding. These parameters
      did not change in unfed control fish. Fed fish likewise increased the net
      titratable base flux to the water by approximately threefold, which resulted in a
      transition from a small net acid flux seen in unfed fish to a large net base flux
      in fed fish. Over 48 h, this resulted in a net excretion of 13 867 micromol kg(
      1) more base to the external water than in unfed fish. The arterial blood
      exhibited a corresponding rise in pH (between 6 and 12 h) and plasma bicarbonate
      (between 3 and 12 h) following feeding; however, no respiratory compensation was
      observed, as PaCO2 remained constant. Overall, there was evidence of numerous
      challenges created by feeding in a freshwater teleost fish, including the
      occurrence of an alkaline tide, and its compensation by excretion of base to the
      external water. The possible influence of feeding ecology and environmental
      salinity on these challenges, as well as discrepancies in the literature, are
      discussed.

PMID- 18626090
TI  - Post-prandial alkaline tide in freshwater rainbow trout: effects of meal
      anticipation on recovery from acid-base and ion regulatory disturbances.
AB  - The post-feeding alkaline tide (elevated blood pH and HCO3-) has been well
      characterised in air-breathing animals, but to date this phenomenon has only been
      demonstrated in one piscine species, a marine elasmobranch. We have investigated
      the acid-base and ion regulatory responses of a freshwater teleost to voluntary
      feeding as well as to involuntary filling of the stomach via an indwelling
      gastric intubation tube. One group of rainbow trout (Oncorhynchus mykiss) were
      fed a 1% body mass ration of homogenised food via the gastric intubation tube.
      Another group fed voluntarily on a 1% body mass ration. Blood samples were taken
      via dorsal aortic catheters from fish in both groups before feeding and over the
      subsequent 72 h. Trout fed via the gastric intubation tube exhibited post
      prandial metabolic alkalosis of the blood (pH and plasma HCO3- increases of up to
      approximately 0.2 pH units and 3 mmol l(-1), respectively), that was more than
      twofold greater than the voluntary feeding fish, and took three times as long to
      recover (72 versus 24 h). Arterial PCO2 was unchanged in both groups indicating
      that freshwater trout do not retain CO2 to compensate for a post-prandial
      alkaline tide. Although excretion of HCO3- to the water increased post
      prandially, NH4+ excretion followed a similar pattern, such that net acid
      equivalent fluxes were unaffected. Thus, sites other than the gills or kidney
      must be responsible for recovery of blood acid-base status, with intestinal HCO3-
      secretion being a likely candidate. In addition, fish fed via the gastric
      intubation tube experienced a large (17 mmol l(-1)) but acute (6 h) drop in
      plasma chloride and a very large (53%) and long lasting decline in plasma
      magnesium concentration, that were absent in voluntarily feeding fish. These
      results further indicate a potentially important role for neuro-endocrine
      mediated mechanisms when fish feed voluntarily, in promoting the earlier
      initiation of compensatory responses that regulate blood ion levels and acid-base
      status. This aspect should also be considered when interpreting studies on other
      aspects of post-prandial physiology, where force feeding by gavage is commonly
      used in preference to voluntary feeding.

PMID- 18626091
TI  - Anterograde and retrograde amnesia of place discrimination in retrosplenial
      cortex and hippocampal lesioned rats.
AB  - Retrograde and anterograde amnesic effects of excitotoxic lesions of the rat
      retrosplenial cortex (RS) and hippocampus (HPC) were investigated. To test
      retrograde amnesia, rats were trained with two-arm place discrimination in a
      radial maze 4 wk and 1 d before surgery with a different arm pair, respectively.
      In the retention test 1 wk after surgery, both lesion groups showed temporally
      ungraded retrograde amnesia. To test anterograde amnesia, animals were trained
      after surgery to discriminate three arm pairs successively within a day, and then
      after interposition of 1- to 4-wk intervals, one of these pairs, respectively,
      was tested for retention. RS-lesioned rats could acquire these pairs of place
      discriminations rapidly but showed a retention interval-dependent impairment in
      the retention test. Conversely, HPC-lesioned rats took more sessions to acquire
      these pairs than did the control group, and their retention was approximately 70%
      of correct performance regardless of retention interval. Results suggest that RS
      and HPC have different roles in spatial memory and that RS is important for
      remote memory process.

PMID- 18626092
TI  - Dopamine D1 and D2 receptors in the nucleus accumbens core and shell mediate
      Pavlovian-instrumental transfer.
AB  - Pavlovian stimuli previously paired with food can markedly elevate the rate of
      food-reinforced instrumental responding. This effect, termed Pavlovian
      instrumental transfer (PIT), depends both on general activating and specific
      cueing properties of Pavlovian stimuli. Recent evidence suggests that the general
      activating properties of Pavlovian stimuli are mediated by mesoaccumbens dopamine
      systems; however, the role of NAC dopamine D1 and D2 receptors is still unknown.
      Here we examined the effects of a selective dopamine D1 and D2 receptor blockade
      in the shell and core subregion of the NAC on general PIT. Rats were trained to
      press a single lever for food, and the effect of a single Pavlovian stimulus
      previously associated with the same food on performance of that lever was
      measured in extinction. Results reveal that PIT, that is, the increase in
      instrumental responding during presentation of the Pavlovian stimulus, was
      reduced by microinjections of the dopamine D1 receptor antagonist SCH-23390 and,
      less pronounced, by microinjections of the dopamine D2 receptor antagonist
      raclopride into the NAC core or shell, respectively. Our data suggest that
      dopamine D1 and D2 receptors in the NAC core and shell mediate the general
      activating effects of Pavlovian stimuli on instrumental behavior.

PMID- 18626093
TI  - Preservation of long-term memory and synaptic plasticity despite short-term
      impairments in the Tc1 mouse model of Down syndrome.
AB  - Down syndrome (DS) is a genetic disorder arising from the presence of a third
      copy of the human chromosome 21 (Hsa21). Recently, O'Doherty and colleagues in an
      earlier study generated a new genetic mouse model of DS (Tc1) that carries an
      almost complete Hsa21. Since DS is the most common genetic cause of mental
      retardation, we have undertaken a detailed analysis of cognitive function and
      synaptic plasticity in Tc1 mice. Here we show that Tc1 mice have impaired spatial
      working memory (WM) but spared long-term spatial reference memory (RM) in the
      Morris watermaze. Similarly, Tc1 mice are selectively impaired in short-term
      memory (STM) but have intact long-term memory (LTM) in the novel object
      recognition task. The pattern of impaired STM and normal LTM is paralleled by a
      corresponding phenotype in long-term potentiation (LTP). Freely-moving Tc1 mice
      exhibit reduced LTP 1 h after induction but normal maintenance over days in the
      dentate gyrus of the hippocampal formation. Biochemical analysis revealed a
      reduction in membrane surface expression of the AMPAR (alpha-amino-3-hydroxy-5
      methyl-4-propionic acid receptor) subunit GluR1 in the hippocampus of Tc1 mice,
      suggesting a potential mechanism for the impairment in early LTP. Our
      observations also provide further evidence that STM and LTM for hippocampus
      dependent tasks are subserved by parallel processing streams.

PMID- 18626094
TI  - Facilitation of taste memory acquisition by experiencing previous novel taste is
      protein-synthesis dependent.
AB  - Very little is known about the biological and molecular mechanisms that determine
      the effect of previous experience on implicit learning tasks. In the present
      study, we first defined weak and strong taste inputs according to measurements in
      the behavioral paradigm known as latent inhibition of conditioned taste aversion.
      We then demonstrated that a strong novel taste input facilitated acquisition of
      the memory of subsequent weak taste input in inverse correlation with the time
      interval between the inputs. However, not only was a strong taste input unable to
      rescue an immediately subsequent strong taste input when the gustatory cortex was
      under the influence of the protein-synthesis inhibitor, anisomycin, but the
      effect of the interaction was to reduce the variation among individual taste
      memories. Taken together, these results demonstrate that taste memory
      facilitation, induced by previously experiencing a different unimodal taste
      input, depended on time, novelty, and directionality. Moreover, the results imply
      that learning is enhanced on the level of acquisition but not of molecular
      consolidation.

PMID- 18626095
TI  - Shifting from implicit to explicit knowledge: different roles of early- and late
      night sleep.
AB  - Sleep has been shown to promote the generation of explicit knowledge as indicated
      by the gain of insight into previously unrecognized task regularities. Here, we
      explored whether this generation of explicit knowledge depends on pre-sleep
      implicit knowledge, and specified the differential roles of slow-wave sleep (SWS)
      vs. rapid eye movement (REM) sleep in this process. Implicit and explicit
      knowledge (insight) related to a hidden regularity were assessed in an
      associative motor-learning task (number reduction task, NRT), which was performed
      in two sessions (initial practice and retest) separated by 3 h of either early
      night sleep, rich in SWS, or of late-night sleep, rich in REM sleep. About half
      of the participants developed signs of implicit rule knowledge (i.e., speeded
      reaction times for responses determined by the hidden regularity) at initial
      practice preceding early or late sleep. Of these, half developed explicit
      knowledge across early-night sleep, significantly more than across late-night
      sleep. In contrast, late-night subjects preferentially remained on the level of
      implicit rule knowledge after sleep. Participants who did not develop implicit
      knowledge before sleep had comparable rates of transition to implicit or explicit
      knowledge across early and late sleep. If subjects gained explicit knowledge
      across sleep, this was associated with lower amounts of REM sleep, specifically
      in the late-night group. SWS predominant during the early night may restructure
      implicit memory representations in a way that allows creating an explicit
      representation afterward, whereas REM sleep in the late night appears to
      stabilize them in their implicit form.

PMID- 18626096
TI  - Medial auditory thalamus inactivation prevents acquisition and retention of
      eyeblink conditioning.
AB  - The auditory conditioned stimulus (CS) pathway that is necessary for delay
      eyeblink conditioning was investigated using reversible inactivation of the
      medial auditory thalamic nuclei (MATN) consisting of the medial division of the
      medial geniculate (MGm), suprageniculate (SG), and posterior intralaminar nucleus
      (PIN). Rats were given saline or muscimol infusions into the MATN contralateral
      to the trained eye before each of four conditioning sessions with an auditory CS.
      Rats were then given four additional sessions without infusions to assess savings
      from the initial training. All rats were then given a retention test with a
      muscimol infusion followed by a recovery session. Muscimol infusions through
      cannula placements within 0.5 mm of the MGm prevented acquisition of eyeblink
      conditioned responses (CRs) and also blocked CR retention. Cannula placements
      more than 0.5 mm from the MATN did not completely block CR acquisition and had a
      partial effect on CR retention. The primary and secondary effects of MATN
      inactivation were examined with 2-deoxy-glucose (2-DG) autoradiography.
      Differences in 2-DG uptake in the auditory thalamus were consistent with the
      cannula placements and behavioral results. Differences in 2-DG uptake were found
      between groups in the ipsilateral auditory cortex, basilar pontine nuclei, and
      inferior colliculus. Results from this experiment indicate that the MATN
      contralateral to the trained eye and its projection to the pontine nuclei are
      necessary for acquisition and retention of eyeblink CRs to an auditory CS.

PMID- 18626098
TI  - Excessive growth.
AB  - Tall stature and excessive growth syndrome are a relatively rare concern in
      pediatric practice. Nevertheless, it is important to identify abnormal
      accelerated growth patterns in children, which may be the clue in the diagnosis
      of an underlying disorder. We present a case of pituitary gigantism in a 2 1/2
      year-old child and discuss the signs, symptoms, laboratory findings, and the
      treatment. Brief discussions on the differential diagnosis of excessive
      growth/tall stature have been outlined. Pituitary gigantism is very rare in the
      pediatrics age group; however, it is extremely rare in a child that is less than
      3 years of age. The nature of pituitary adenoma and treatment options in children
      with this condition have also been discussed.

PMID- 18626097
TI  - c-Rel, an NF-kappaB family transcription factor, is required for hippocampal long
      term synaptic plasticity and memory formation.
AB  - Transcription is a critical component for consolidation of long-term memory.
      However, relatively few transcriptional mechanisms have been identified for the
      regulation of gene expression in memory formation. In the current study, we
      investigated the activity of one specific member of the NF-kappaB transcription
      factor family, c-Rel, during memory consolidation. We found that contextual fear
      conditioning elicited a time-dependent increase in nuclear c-Rel levels in area
      CA1 and DG of hippocampus. These results suggest that c-rel is active in
      regulating transcription during memory consolidation. To identify the functional
      role of c-Rel in memory formation, we characterized c-rel(-/-) mice in several
      behavioral tasks. c-rel(-/-) mice displayed significant deficits in freezing
      behavior 24 h after training for contextual fear conditioning but showed normal
      freezing behavior in cued fear conditioning and in short-term contextual fear
      conditioning. In a novel object recognition test, wild-type littermate mice
      exhibited a significant preference for a novel object, but c-rel(-/-) mice did
      not. These results indicate that c-rel(-/-) mice have impaired hippocampus
      dependent memory formation. To investigate the role of c-Rel in long-term
      synaptic plasticity, baseline synaptic transmission and long-term potentiation
      (LTP) at Schaffer collateral synapses in c-rel(-/-) mice was assessed. c-rel(-/-)
      slices had normal baseline synaptic transmission but exhibited significantly less
      LTP than did wild-type littermate slices. Together, our results demonstrate that
      c-Rel is necessary for long-term synaptic potentiation in vitro and hippocampus
      dependent memory formation in vivo.

PMID- 18626099
TI  - Two Children with macrocephaly, developmental delay, and PTEN mutation.

PMID- 18626100
TI  - A child with severe joint pain.

PMID- 18626101
TI  - Bizarre bezoar: case report of a gastric dehydrated-fruit bezoar in an infant.

PMID- 18626102
TI  - Initial fluid resuscitation for patients with diabetic ketoacidosis: how dry are
      they?
AB  - A prospective consecutive case series of patients aged 5 to 20 years who
      presented to a pediatric emergency department with diabetic ketoacidosis (DKA)
      was studied to determine the actual percent loss of body weight during an episode
      of DKA to determine the degree of dehydration and thereby provide a guide for
      hydration therapy during such an episode. Patients' weights at the time of
      presentation, inpatient discharge, and at the first follow-up clinic visit were
      used to calculate the percent loss of body weight. Data from 33 episodes of DKA
      showed that the majority of patients with DKA had moderate (4% to 8%)
      dehydration. Clinical assessment was a poor predictor of severity of dehydration
      and overestimated the percent dehydration in 67% of patients. Based on these data
      it is recommend that initial fluid therapy for DKA should assume moderate
      dehydration with adjustment made according to clinical response.

PMID- 18626103
TI  - A violence-prevention program helps teach medical students and pediatric
      residents about childhood aggression.
AB  - There were 65 third-year medical students and 59 pediatric residents who
      participated. The intervention was a 40-minute multimedia program that teaches
      how to counsel parents about childhood aggression. Comparing pre- and 2-month
      postintervention data, there was an increase in the proportion of medical
      students (11% pre vs 92% post; P < .001) and residents (3% pre vs 95% post; P <
      .001) who felt that their ability to counsel parents about hurtful behavior was
      high or very high. Compared with baseline, a higher proportion of trainees at the
      2-month follow-up recommended redirecting (11% pre vs 69% post; P < .001),
      promoting empathy (13% pre vs 42% post; P < .001), and not using physical
      punishment (25% pre vs 50% post; P < .001). A brief, independently viewed
      curriculum addition expanded the repertoire of health care trainees related to
      counseling parents about childhood aggression. These findings have implications
      for violence prevention.

PMID- 18626104
TI  - Back abscess.

PMID- 18626105
TI  - Venous hum causing tinnitus: case report and review of the literature.
AB  - Hearing one's own heart murmur has been reported in adults, but has not been
      reported in the pediatric literature. This study reports the case of a young
      child who clearly heard her own venous hum, causing her to complain of pulsatile
      tinnitus. This entity should be included in the differential diagnosis of
      pulsatile tinnitus and by doing so pediatricians and cardiologists may avoid
      ordering unnecessary diagnostic procedures.

PMID- 18626106
TI  - Utility of store-and-forward pediatric telecardiology evaluation in
      distinguishing normal from pathologic pediatric heart sounds.
AB  - Because pediatric cardiologists can accurately diagnose innocent murmurs by
      physical exam alone, the authors developed a system for remote cardiac
      auscultation. They hypothesized that their system could accurately classify
      auscultatory findings as normal/innocent or pathologic. Patients undergoing
      evaluation underwent examination, echocardiography, and heart sound recording.
      Pediatric cardiologists evaluated the heart sounds and classified the case as
      either normal/innocent or pathologic. They reviewed103 heart sound data sets; 85%
      of the cases were accurately classified as either normal/innocent or pathologic,
      with a sensitivity of 82% and specificity of 86%. However, when accounting for
      clinical diagnosis, reviewer uncertainty, and ECG abnormalities, the sensitivity
      and specificity improved to 91% and 88% (accuracy 89%), respectively. Degree of
      certainty with the telecardiology diagnosis correlated with correct
      interpretation (P < .005). Digital heart sound recordings evaluated via
      telemedicine can distinguish normal/innocent murmurs from pathologic ones. Such a
      system could improve the use of pediatric cardiology services.

PMID- 18626107
TI  - Sources of knowledge transfer among primary care pediatric health care providers.
AB  - OBJECTIVES: The authors sought to understand which informational sources
      pediatric health care providers perceive as most influential in how they stay
      current with health care innovations. METHODS: Rochester, New York, area
      pediatric health care providers were surveyed using a self-administered
      questionnaire. Two items pertained to the health care provider's ability to
      interpret primary research, and 9 items pertained to the influence and relative
      importance of various sources of information. RESULTS: A 61% response rate was
      obtained. Most (83%) respondents felt adequately trained to interpret primary
      research, fewer (31%) felt they have the time to do so. Almost all respondents
      (92%) felt that American Academy of Pediatrics (AAP) guidelines were a major
      influence, and 44% felt that AAP guidelines were the single most influential
      source of information in how they altered their practice over time. CONCLUSIONS:
      In the setting of time constraints, and the volume and complexity of published
      therapeutic research, AAP guidelines are playing an increasing role in knowledge
      transfer.

PMID- 18626108
TI  - Ibuprofen-induced liver injury in an adolescent athlete.

PMID- 18626109
TI  - Rural school-based telehealth: how to make it happen.
AB  - When organizing new health care interventions among a rural population, a careful
      planning process respecting community-specific considerations should be used. The
      project objective centered on the successful implementation of a school-based
      telehealth clinic serving a rural, health-disparate population. Using an American
      Academy of Pediatrics Community Access to Child Health planning grant, a needs
      assessment of the Delta community was conducted. In synthesizing the results of
      this planning project, consensually addressed issues led to establishing a pilot
      school-based telehealth clinic within the rural county schools. Seven essential
      steps emerged as a set of guidelines that entities might consider in introducing
      a telemedicine school-based service in a rural community. The steps included
      assessing local and regional needs, securing community support and establishing
      goals, evaluating resources, configuring logistics, training staff, informing
      parents, and launching the clinic. Proper planning is crucial to the
      establishment of a rural school-based telehealth clinic.

PMID- 18626110
TI  - Hemihypertrophy in a neonate.

PMID- 18626111
TI  - Surrogate decision making for the previously capable minor.
AB  - An older-adolescent patient becomes incapable of making medical decisions due to
      the progression of his illness. The medical team members are faced with a
      conflict between what the law requires and their ethical convictions regarding
      who should be the surrogate decision maker. A discussion of relevant law and
      ethical standards is presented as it applies to similar situations.

PMID- 18626112
TI  - A TR3/Nur77 peptide-based high-throughput fluorescence polarization screen for
      small molecule Bcl-B inhibitors.
AB  - Nuclear receptor TR3/Nur77/NR4A1 binds several antiapoptotic Bcl-2-family
      proteins (Bcl-B, Bcl-2, Bfl-1) in a non-BH3-dependent manner. A 9-amino-acid
      peptide derived from full-length TR3 with polyarginine tail (TR3-r8)
      recapitulates TR3's binding specificity, displaying high affinity for Bcl-B. TR3
      r8 peptide was used to screen for small molecule Bcl-B inhibitors. A fluorescence
      polarization assay (FPA) employing fluorescein isothiocyanate (FITC)-labeled TR3
      r8 peptide (FITC-TR3-r8) and Bcl-B protein was optimized, with nonfluorescent TR3
      r8 serving to demonstrate reversible, competitive binding. Approximately 50,000
      compounds were screened at 3.75 mg/L, yielding 145 reproducible hits with > or
      =50% FITC-TR3-r8 displacement (a confirmed hit rate of 0.29%). After dose
      response analyses and counterscreening with an unrelated FITC-based FPA, 6
      candidate compounds remained. Nuclear magnetic resonance (NMR) showed that 2 of
      these compounds bound Bcl-B, but not glutathione S-transferase (GST) control
      protein. One Bcl-B-binding compound was unable to displace FITClabeled BH3
      peptides from Bcl-B, confirming a unique binding mechanism compared with
      traditional antagonists of antiapoptotic Bcl-2-family proteins. This compound
      bound Bcl-B with Kd 1.94 +/- 0.38 microM, as determined by isothermal titration
      calorimetry. Experiments using Bcl-B overexpressing HeLa cells demonstrated that
      this compound induced Bcl-B-dependent cell death. The current FPA represents a
      screen that can identify noncanonical inhibitors of Bcl-2-family proteins.

PMID- 18626113
TI  - HTRF-based assay for microsomal prostaglandin E2 synthase-1 activity.
AB  - Microsomal prostaglandin E2 synthase-1 (mPGES-1) catalyzes the formation of
      prostaglandin E2 (PGE2) from the endoperoxide prostaglandin H2 (PGH2). Expression
      of this enzyme is induced during the inflammatory response, and mouse knockout
      experiments suggest it may be an attractive target for antiarthritic therapies.
      Assaying the activity of this enzyme in vitro is challenging because of the
      unstable nature of the PGH2 substrate. Here, the authors present an mPGES-1
      activity assay suitable for characterization of enzyme preparations and for
      determining the potency of inhibitor compounds. This plate-based competition
      assay uses homogenous time-resolved fluorescence to measure PGE2 produced by the
      enzyme. The assay is insensitive to DMSO concentration up to 10% and does not
      require extensive washes after the initial enzyme reaction is concluded, making
      it a simple and convenient way to assess mPGES-1 inhibition.

PMID- 18626115
TI  - A high-throughput screening assay for small molecules that disrupt yeast cell
      integrity.
AB  - Lead compounds for antifungal drug development are urgently needed because
      invasive fungal infections are an important cause of morbidity and mortality in
      immunocompromised patients. Here, a high-throughput screening assay for small
      molecules that cause yeast cell lysis is described. The assay is based on the
      detection of the intracellular enzyme adenylate kinase in the culture medium as a
      reporter of yeast cell lysis. Features of the assay protocol include 1) the
      ability to detect cell lysis at drug concentrations that cause no apparent growth
      defect, 2) specificity for fungicidal molecules, 3) a simple 1-plate, add-and
      read protocol using a commercially available adenylate kinase assay kit, 4)
      short, 5-h incubation time, and 5) low cost. The assay is applicable to the model
      yeast Saccharomyces cerevisiae and to Candida albicans, the most common human
      fungal pathogen. The adenylate kinase assay is validated in a pilot screen of
      4505 compounds. Consistent with its specificity for fungicidal molecules, the
      largest class of molecules identified in 2 libraries of known bioactive molecules
      targeted the plasma membrane. Fungistatic compounds are not detected by the
      assay. Adenylate kinase-based screening appears to be a useful approach to the
      direct identification of small molecules that kill yeast cells.

PMID- 18626116
TI  - A novel method for determination of the affinity of protein: protein interactions
      in homogeneous assays.
AB  - Nonradioactive homogeneous assays are widely used to screen for inhibitors of
      biomolecular interactions. To ensure optimal sensitivity for the detection of
      competitive inhibitors, reagent concentrations should be fixed at or below the
      K(D) of the protein-protein interaction. Accurate measurement of K(D) during
      assay development is therefore critical. Although conventional methods work well
      with heterogeneous assays, they are generally unsatisfactory with homogeneous
      systems. Here the authors describe an alternative method to determine the K(D) of
      protein-protein interactions in homogeneous assays. The method uses a
      rearrangement of the Cheng-Prusoff equation: IC50= (([Ki]/K(D)) x [L]) + Ki. A
      competitive inhibitor is titrated into the ligand-receptor binding assay at a
      range of ligand concentrations and IC50 values are calculated. Plotting measured
      IC50 versus concentration of ligand gives a linear plot with y-intercept (Ki) and
      gradient (Ki/K(D)). K(D) is the affinity constant for the ligand-receptor
      interaction. Here the authors use homogeneous time-resolved fluorescence (HTRF)
      in 2 model systems (TRAIL/TRAIL receptor 4 and OX40 ligand/OX40 receptor) and
      demonstrate that measured K(D) values calculated using the linearized Cheng
      Prusoff plot compare favorably with those from independent experiments. The
      advantages and limitations of the method are discussed.

PMID- 18626114
TI  - High-throughput screening-based identification of paramyxovirus inhibitors.
AB  - Several members of the paramyxovirus family constitute major human pathogens
      that, collectively, are responsible for major morbidity and mortality worldwide.
      In an effort to develop novel therapeutics against measles virus (MV), a
      prominent member of the paramyxovirus family, the authors report a high
      throughput screening protocol that uses a nonrecombinant primary MV strain as
      targets. Implementation of the assay has yielded 60 hit candidates from a 137,500
      entry library. Counterscreening and generation of dose-response curves narrows
      this pool to 35 compounds with active concentrations < or =15.3 microM against
      the MV-Alaska strain and specificity indices ranging from 36 to >500. Library
      mining for structural analogs of several confirmed hits combined with retesting
      of identified candidates reveals a high accuracy of primary hit identification.
      Eleven of the confirmed hits interfere with viral entry, whereas the remaining 24
      compounds target postentry steps of the viral life cycle. Activity testing
      against selected members of the paramyxovirus family reveals 3 patterns of
      activity: 1) exclusively MV-specific blockers, 2) inhibitors of MV and related
      viruses of the same genus, and 3) broader range inhibitors with activity against
      a different Paramyxovirinae genus. Representatives of the last class may open
      avenues for the development of broad-range paramyxovirus inhibitors through hit
      to-lead chemistry.

PMID- 18626117
TI  - Profiling protein tyrosine phosphorylation: a quantitative 45-plex peptide-based
      immunoassay.
AB  - Cellular homeostasis and responses to stimuli are mediated by complex signaling
      network events dominated by changes in protein phosphorylation states.
      Understanding information flow in the network is essential for correlating
      signaling changes to cell physiology. Tyrosine phosphorylation constitutes only a
      small portion of all protein phosphorylation, but its importance is manifested by
      the significant role it plays in diseases such as cancer. A peptide-based
      immunoassay microarray, designed to provide site specificity, quantification,
      broad coverage, and accessibility, is described that profiles 45 tyrosine
      phosphorylation sites across 34 proteins. Epidermal growth factor-stimulated A431
      cells in the absence and presence of kinase inhibitors analyzed by microarrays
      showed biologically validated tyrosine phosphorylation changes and unanticipated
      activation of other targets. The approach is scalable for increasing the breadth
      of content as well as for interrogating other types of protein posttranslational
      modifications.

PMID- 18626118
TI  - Perceptions of health, HIV disease, and HIV treatment by patients in 6 regions:
      analysis of the 2555-person AIDS treatment for life international survey.
AB  - BACKGROUND: Antiretroviral therapy (ART) has reached millions of HIV-infected
      patients worldwide, however very little is known about their perceptions about
      HIV disease and its treatment. The AIDS Treatment for Life International Survey
      (ATLIS) is the largest sampling of patient perceptions about HIV disease and its
      treatment, as well as their behaviors, including HIV status disclosure and ART
      adherence. METHODS: The International Association of Physicians in AIDS Care
      (IAPAC) and its survey vendor, Ipsos Insight Health, conducted a convenience
      sample survey of 2555 treated and untreated HIV-infected adults recruited by
      diverse means from 6 regions: North America, Latin America, the Caribbean,
      Europe, Asia/Pacific, and sub-Saharan Africa. FINDINGS: Nearly three quarters of
      respondents were taking prescription medications for HIV infection or related
      diseases. Participants reported generally good overall health and high degrees of
      satisfaction with current antiretroviral drugs, though approximately half of
      respondents voiced concern about potential ART toxicity and 39.4% reported
      switching their antiretroviral regimen specifically because of treatment
      associated side effects. About 1 in 5 respondents never took medications for HIV
      and AIDS. Among the three quarters of respondents currently taking medications,
      37% are taking their first prescribed antiretroviral regimen, and 24% have
      switched from a first-line antiretroviral regimen. Three quarters of respondents
      believe ART will help them live a long life, and treatment-experienced
      respondents expressed this view significantly more often than untreated
      respondents. Large majorities of respondents in Latin America, Asia, and South
      Africa want to know more about ART, while half or fewer in these countries
      correctly explained the meaning of undetectable HIV RNA (defined as <50 HIV RNA
      copies/mL of plasma) or knew their CD4 cell count.

PMID- 18626119
TI  - Profile of communication disorders in HIV-infected individuals: a preliminary
      study.
AB  - Communication is the very essence of life for humans. This is made possible by
      the highly complex neurophysiological mechanisms governing humans. Any
      disturbance to this system can result in impairments of communication. HIV
      infection is one such disease. In India, the management of such individuals is
      usually restricted to life sustenance. Little importance is given to their
      communication problems, which play a vital role in day-to-day functioning. It is
      with this background that this study was conducted. Eight HIV-infected
      individuals participated in the study. They were subjected to assessment
      procedures that included the following tests: Western Aphasia Battery, Frenchay
      Dysarthria Assessment, Standard Articulation test, Fluency test, and subjective
      assessment of vocal parameters by a speech language pathologist. The results of
      the study reveal that individuals with HIV-1 infection show a varied picture of
      affected parameters of voice, swallowing, and oral motor functioning.

PMID- 18626120
TI  - Characteristics of patients accessing care and treatment for HIV/AIDS at public
      and nongovernmental sites in South Africa.
AB  - Little is known about the characteristics of patients accessing antiretroviral
      therapy (ART) in South Africa. In a random sample of 1069 pre-ART and ART
      patients attending an urban public hospital, a periurban nongovernmental
      organization (NGO) clinic, and a rural NGO clinic, 79% were female; average age
      was 34 for women and 37 for men. Two thirds reported having 1 long-term partner,
      but most did not live with their partner. Three fourths had completed some
      secondary school or higher; 47% were employed formally (26%) or informally (21%),
      and 40% lived in informal housing or shacks. Patients at the rural site were less
      likely to be employed and more likely to receive government grant support.
      Relative to the HIV-positive population as a whole, ART patients are older, more
      likely to be female and have 1 long-term partner, live in informal housing, have
      reached secondary school, and earn an income from formal or informal employment.

PMID- 18626121
TI  - Hepatic ultrastructural mitochondrial changes prior to antiretroviral therapy in
      HIV-infected patients in Brazil.
AB  - The use of antiretroviral (ARV) medications has been linked to the emergence of
      severe adverse effects, including mitochondrial toxicity. The liver also appears
      to be among the affected organs. Nevertheless, different studies suggest that
      these patients' mitochondrial alterations could be associated to other
      etiological factors. The goal of this study was to analyze hepatic mitochondria
      ultrastructural changes in HIV-infected patients under investigation for
      hepatopathy. Semiquantitative analysis of mitochondria was performed in liver
      biopsies from 10 patients divided into 2 groups: Group 1 consisted of 5 patients
      who had never used ARV medications; group 2 consisted of 5 patients who reported
      previous use of either zidovudine or didanosine. Significant mitochondrial
      alterations were found in both groups. The summation of the mitochondrial
      alterations was higher in group 1 (P < .05) when compared with those who had
      previously used ARV medications. Therefore, the authors conclude that severe
      mitochondrial alterations occur in HIV-infected patients who have never been
      submitted to antiretroviral therapy.

PMID- 18626122
TI  - Acute kidney disease due to immune reconstitution inflammatory syndrome in an HIV
      infected patient with tuberculosis.
AB  - This study reports the case of an HIV-infected patient with disseminated
      tuberculosis who presented an immune reconstitution inflammatory syndrome (IRIS)
      revealed by an acute kidney disease 45 and 15 days after initiation of
      antituberculosis therapy and HAART, respectively. Prednisone therapy and the
      transient withdrawal of HAART improved the renal function and the clinical
      condition of this patient. All published case reports of IRIS revealed by acute
      renal failure in HIV-infected patients are also reviewed.

PMID- 18626123
TI  - Validity of self-reported adherence among injection drug users.
AB  - BACKGROUND: In Vancouver, the availability of prescription refill data for all
      HIV-infected individuals plus a prospective cohort of injection drug users (IDUs)
      permitted an examination of the validity of self-reported highly active
      antiretroviral therapy (HAART) adherence among IDUs. METHODS: Self-reported HAART
      adherence among Vancouver Injection Drug Users Study participants was compared
      with pharmacy refill rates from the British Columbia Drug Treatment Program
      database. Pearson's correlation coefficient and Pearson's chi(2) test were used
      to assess associations between adherence as measured by self-report and pharmacy
      refill data. RESULTS: Among 88 HIV-infected IDUs, 48 (55%) had an adherence rate
      of > or =75% as measured by pharmacy refill adherence, whereas 81 (92%) had an
      adherence rate of > or =75% as measured by self-report. Self-reported adherence
      was not statistically associated with pharmacy refill adherence (P > .1).
      CONCLUSION: These findings suggest that the validity of self-report measures may
      be limited when applied to community-recruited IDUs.

PMID- 18626124
TI  - Monitoring adherence and defaulting for antiretroviral therapy in 5 East african
      countries: an urgent need for standards.
AB  - OBJECTIVES: A cross-sectional survey was performed in 24 systems of care
      providing antiretroviral medications in Ethiopia, Kenya, Rwanda, Tanzania, and
      Uganda to examine current practices in monitoring rates of treatment adherence
      and defaulting. RESULTS: Only 20 of 48 facilities reported routinely measuring
      individual patient adherence levels; only 12 measured rates of adherence for the
      clinic population. The rules for determining which patients were included in the
      calculation of rates were unclear. Fourteen different definitions of treatment
      defaulting were in use. Facilities routinely gather potentially useful data, but
      the frequency of doing so varied widely. CONCLUSIONS: Individual and program
      treatment adherence and defaulting are not routinely monitored; when done, the
      operational definitions and methods varied widely, making comparisons across
      programs unreliable. There is a pressing need to determine which measures are the
      most feasible and reliable to collect, the most useful for clinical counseling,
      and most informative for program management.

PMID- 18626125
TI  - Targeting points for further intervention: a review of HIV-infected infants born
      in ireland in the 7 years following introduction of antenatal screening.
AB  - Even in countries with well-developed programs for prevention of mother-to-child
      transmission (MTCT) of HIV, there remains a low level of ongoing transmission.
      Pregnant, HIV-infected women may not always access screening and available
      interventions because of circumstances, beliefs, and other influences. Missed
      opportunities for the prevention of MTCT remains an issue to be addressed.
      Through a review of HIV-infected children born during the years of antenatal
      screening in Ireland, we sought to identify further targets for intervention to
      further reduce MTCT.

PMID- 18626126
TI  - The impact of individualized evidence-based decision support on aneurysm
      patients' decision making, ideals of autonomy, and quality of life.
AB  - BACKGROUND: Patients with an asymptomatic abdominal aneurysm and their surgeon
      were randomized to receive a general brochure (GB) or an IB presenting survival
      information and a ranking of the treatment strategies. Before and after receiving
      the brochure, patients filled out questionnaires on their behavior during the
      consultation, ideals of patient autonomy, and quality of life. Surgeons answered
      a short checklist evaluating the consultation. RESULTS: One hundred patients
      participated, 49 in the intervention, 51 in the control group. The IB group had a
      better understanding of important issues in the treatment decision, had prepared
      more questions, and was less satisfied with the duration of the consultation.
      Their impression that the surgeon perceived them more as a medical problem than a
      patient with a problem increased. They agreed less with the surgeon's advice and
      lost some of their belief in "the doctor knows best.'' Beforehand, the IB group
      had a stronger preference for patient-based decisions, but afterward they
      displayed more surgeon-based decisions. No effects were seen on patients' quality
      of life. CONCLUSIONS: Individualized evidence-based information stimulated
      patients' active involvement but in the context of our study led to less patient
      based decisions. Patient-made decisions and patient autonomy should, however, not
      be equated.

PMID- 18626127
TI  - Markov chain models of coupled calcium channels: Kronecker representations and
      iterative solution methods.
AB  - Mathematical models of calcium release sites derived from Markov chain models of
      intracellular calcium channels exhibit collective gating reminiscent of the
      experimentally observed phenomenon of stochastic calcium excitability (i.e.,
      calcium puffs and sparks). Calcium release site models are stochastic automata
      networks that involve many functional transitions, that is, the transition
      probabilities of each channel depend on the local calcium concentration and thus
      the state of the other channels. We present a Kronecker-structured representation
      for calcium release site models and perform benchmark stationary distribution
      calculations using both exact and approximate iterative numerical solution
      techniques that leverage this structure. When it is possible to obtain an exact
      solution, response measures such as the number of channels in a particular state
      converge more quickly using the iterative numerical methods than occupation
      measures calculated via Monte Carlo simulation. In particular, multi-level
      methods provide excellent convergence with modest additional memory requirements
      for the Kronecker representation of calcium release site models. When an exact
      solution is not feasible, iterative approximate methods based on the power method
      may be used, with performance similar to Monte Carlo estimates. This suggests
      approximate methods with multi-level iterative engines as a promising avenue of
      future research for large-scale calcium release site models.

PMID- 18626129
TI  - Model of reduction of actin polymerization forces by ATP hydrolysis.
AB  - The effects of hydrolysis of ATP-actin to ADP-actin on actin polymerization-based
      force generation are calculated using a multifilament two-state Brownian ratchet
      model. The model treats an ensemble of rigid parallel filaments growing against a
      hard, inert, diffusing obstacle held in an optical trap. The filaments
      stochastically grow, depolymerize and undergo transitions between polymerizing
      and depolymerizing tip states. The parameters in the model are obtained from
      literature values and a fit to the measured dependence of the polymerization rate
      on the free-actin concentration. For more than two filaments, the stall force per
      filament near the critical concentration is much less than the equilibrium ATP
      actin stall force. By reducing the availability of free monomers, the obstacle
      causes filament tips to convert to the depolymerizing state, so that only a small
      fraction of the filaments contact the obstacle at a given time.

PMID- 18626128
TI  - A possible mechanism for self-coordination of bidirectional traffic across
      nuclear pores.
AB  - Nuclear pore complexes are constantly confronted by large fluxes of
      macromolecules and macromolecular complexes that need to get into and out of the
      nucleus. Such bidirectional traffic occurring in a narrow channel can easily lead
      to jamming. How then is passage between the nucleus and cytoplasm maintained
      under the varying conditions that arise during the lifetime of the cell? Here, we
      address this question using computer simulations in which the behaviour of the
      ensemble of transporting cargoes is analysed under different conditions. We
      suggest that traffic can exist in two distinct modes, depending on the
      concentration of cargoes and dissociation rates of the transport receptor-cargo
      complexes from the pores. In one mode, which prevails when dissociation is quick
      and cargo concentration is low, transport in either direction proceeds
      uninterrupted by transport in the other direction. The result is that the overall
      traffic direction fluctuates rapidly and unsystematically between import and
      export. Remarkably, when cargo concentrations are high and disassociation is
      slow, another mode takes over in which traffic proceeds in one direction for a
      certain extent of time, after which it flips direction for another period. The
      switch between this, more regulated, mode of transport and the other, quickly
      fluctuating state, does not require an active gating mechanism but rather occurs
      spontaneously through the dynamics of the transported particles themselves. The
      determining factor for the behaviour of traffic is found to be the exit rate from
      the pore channel, which is directly related to the activity of the Ran system
      that controls the loading and release of cargo in the appropriate cellular
      compartment.

PMID- 18626130
TI  - Fish and chips: implementation of a neural network model into computer chips to
      maximize swimming efficiency in autonomous underwater vehicles.
AB  - Recent developments in the design and propulsion of biomimetic autonomous
      underwater vehicles (AUVs) have focused on boxfish as models (e.g. Deng and
      Avadhanula 2005 Biomimetic micro underwater vehicle with oscillating fin
      propulsion: system design and force measurement Proc. 2005 IEEE Int. Conf. Robot.
      Auto. (Barcelona, Spain) pp 3312-7). Whilst such vehicles have many potential
      advantages in operating in complex environments (e.g. high manoeuvrability and
      stability), limited battery life and payload capacity are likely functional
      disadvantages. Boxfish employ undulatory median and paired fins during routine
      swimming which are characterized by high hydromechanical Froude efficiencies
      (approximately 0.9) at low forward speeds. Current boxfish-inspired vehicles are
      propelled by a low aspect ratio, 'plate-like' caudal fin (ostraciiform tail)
      which can be shown to operate at a relatively low maximum Froude efficiency
      (approximately 0.5) and is mainly employed as a rudder for steering and in rapid
      swimming bouts (e.g. escape responses). Given this and the fact that bioinspired
      engineering designs are not obligated to wholly duplicate a biological model,
      computer chips were developed using a multilayer perception neural network model
      of undulatory fin propulsion in the knifefish Xenomystus nigri that would
      potentially allow an AUV to achieve high optimum values of propulsive efficiency
      at any given forward velocity, giving a minimum energy drain on the battery. We
      envisage that externally monitored information on flow velocity (sensory system)
      would be conveyed to the chips residing in the vehicle's control unit, which in
      turn would signal the locomotor unit to adopt kinematics (e.g. fin frequency,
      amplitude) associated with optimal propulsion efficiency. Power savings could
      protract vehicle operational life and/or provide more power to other functions
      (e.g. communications).

PMID- 18626131
TI  - Towards bioinspired superhydrophobic poly(L-lactic acid) surfaces using phase
      inversion-based methods.
AB  - The water repellency and self-cleaning ability of many biological surfaces has
      inspired many fundamental and practical studies related to the development of
      synthetic superhydrophobic surfaces. However, the investigation of such
      substrates made of biodegradable polymers has been scarce. Simple approaches
      based on a single step, performed at room temperature (and pressure), were
      implemented to obtain superhydrophobic poly(L-lactic acid) (PLLA) surfaces via
      phase inversion-based methods, without addition of low-surface-energy compounds.
      Water contact angles above 150 degrees were obtained using some processing
      conditions. In such cases scanning electronic microscopy micrographs of such
      surfaces revealed a clear rough texture composed by leafy clusters with micro
      nano binary structures. Such materials could be used in specific environmental
      and biomedical applications, namely in implantable materials or in antibacterial
      or antithrombogenic surfaces.

PMID- 18626132
TI  - Human ocular counter-rolling and roll tilt perception during off-vertical axis
      rotation after spaceflight.
AB  - Ocular counter-rolling (OCR) induced by whole body tilt in roll has been explored
      after spaceflight as an indicator of the adaptation of the otolith function to
      microgravity. It has been claimed that the overall pattern of OCR responses
      during static body tilt after spaceflight is indicative of a decreased role of
      the otolith function, but the results of these studies have not been consistent,
      mostly due to large variations in the OCR within and across individuals. By
      contrast with static head tilt, off-vertical axis rotation (OVAR) presents the
      advantage of generating a sinusoidal modulation of OCR, allowing averaged
      measurements over several cycles, thus improving measurement accuracy.
      Accordingly, OCR and the sense of roll tilt were evaluated in seven astronauts
      before and after spaceflight during OVAR at 45 degrees/s in darkness at two
      angles of tilt (10 degrees and 20 degrees). There was no significant difference
      in OCR during OVAR immediately after landing compared to preflight. However, the
      amplitude of the perceived roll tilt during OVAR was significantly larger
      immediately postflight, and then returned to control values in the following
      days. Since the OCR response is predominantly attributed to the shearing force
      exerted on the utricular macula, the absence of change in OCR postflight suggests
      that the peripheral otolith organs function normally after short-term
      spaceflight. However, the increased sense of roll tilt indicates an adaptation in
      the central processing of gravitational input, presumably related to a re
      weighting of the internal representation of gravitational vertical as a result of
      adaptation to microgravity.

PMID- 18626133
TI  - Static and dynamic vestibulo-cervico-ocular responses after prolonged exposure to
      microgravity.
AB  - The vestibular function was investigated in 13 Russian crew members of the ISS
      missions on days 1(2), 4(5), and 8(9) after prolonged exposure to microgravity
      (126 to 195 days). The static torsional otolith-cervico-ocular reflex was
      studied, as well as the dynamic vestibulo-cervico-ocular responses, vestibular
      reactivity, and spontaneous oculomotor activity using videooculography (VOG) and
      electrooculography (EOG) for simultaneous recording of eye movements. On days 1-2
      of return to the gravity (R+1-2), the cosmonauts were found to increase the
      spontaneous oculomotor activity (floating eye movements, both typical and
      atypical forms of spontaneous nystagmus, square wave jerks, gaze nystagmus) with
      the head held in the vertical position. The otolith function during static head
      inclinations to the right or left shoulder at 30 degrees was suppressed as
      determined by the inversion or absence, or reduction by half of the amplitude of
      torsional compensatory eye counter-rolling and the vestibular reactivity during
      head yaw movements at 0.125 Hz was increased as revealed by a lowered threshold
      and an increased intensity of vestibular nystagmus. The pattern, depth, dynamics,
      and velocity of the vestibular function recovery varied with individual
      participants in the investigation. However, the suppressed otolith functioning in
      the period of readaptation to the normal gravity was, as a rule, accompanied by
      an exaggerated vestibular reactivity.

PMID- 18626134
TI  - Effects of vestibular training on motion sickness, nystagmus, and subjective
      vertical.
AB  - Pitch head-and-trunk movements during constant velocity rotation are a
      provocative vestibular stimulus that produces vertigo and nausea. When exposed to
      this stimulus repeatedly, motion sickness symptoms diminish as the subjects
      habituate. Acetylleucine is a drug that is used to treat acute vestibular
      vertigo. In this study, we wanted to ascertain whether this drug (a) lessened
      motion sickness or delayed habituation; (b) accelerated the recovery following
      habituation; and (c) whether changes in the subjective vertical accompanied
      habituation. Twenty subjects were administered acetylleucine or placebo in a
      double-blind study during a five-day vestibular training. Horizontal vestibulo
      ocular reflex, optokinetic nystagmus, smooth pursuit, and subjective visual
      vertical were evaluated before, during, and up to two months after the vestibular
      training. Based on Graybiel's diagnostic criteria, motion sickness decreased
      steadily in each vestibular training session, and there was no difference between
      the scores in the acetylleucine and placebo groups. Post-rotatory nystagmus peak
      velocity and time constant also declined in both groups at the same rate. Thus,
      acetylleucine neither reduced the nausea associated with this provocative
      stimulus, nor hastened the acquisition or retention of vestibular habituation of
      motion sickness and nystagmus. There was no difference in optokinetic nystagmus
      and smooth pursuit between the acetylleucine and placebo groups. However,
      subjects showed larger error in the subjective visual vertical after habituation,
      which indicates that spatial orientation is also affected by vestibular training.

PMID- 18626135
TI  - One second interval production task during post-rotatory sensation.
AB  - Temporal intervals production of one second was found to be more variable during
      self-motion compared to no motion situations. Moreover, the temporal intervals
      production rhythm during self-motion deceleration decreased whereas it increased
      during self-motion acceleration, whatever the direction of motion. As
      somatosensory cues were not excluded in this previous experiment, we now examined
      whether the same temporal perturbation would occur without variable somatosensory
      information. In order to isolate the contribution of the vestibular system from
      that of the somatosensory system, the participants were required to perform a one
      second temporal interval production task (pressing a button each second) during
      the post-rotatory illusion following self-rotation. The intervals produced during
      the vestibular illusion were compared to those produced before the imposed
      rotation and during self-motion. The production regularity was affected as the
      temporal intervals were more variable with vestibular stimulation (real and
      illusory self-motion) than without. Furthermore, during post-rotatory illusion,
      the production rhythm decreased along the trial, as it was observed during self
      motion deceleration. These findings suggest that vestibular stimulation (even
      vestibular illusion) impaired time estimation.

PMID- 18626136
TI  - Perceptual centering of body segment orientation.
AB  - It has been shown experimentally that under certain combinations of sensory
      stimuli, human subjects can perceive one of several distinct illusions about
      their overall orientation in or movement through space. In at least some cases,
      the structure of such multistable illusory perceptions of orientation can be
      efficiently described by perceptual transformations that act on a current
      orientation estimate to yield an updated perceptual construct. Repeated
      application of identified generating transformations yields a limited set of
      predicted illusions for a given sensory environment. This approach is especially
      valuable for perceptual data that exhibits discretely differing classes of
      illusions between subjects or trials. In a previous study, application of a
      semigroup of perceptual centering transformations has succeeded in reproducing
      and simplifying data from an experiment in which subjects experiencing visual
      vection reported a range of illusions about the orientations of their gaze, head,
      and torso to gravity. After reviewing previously obtained results on perceptual
      centering, this article generalizes the approach, presenting the mathematics
      required to characterize perceptual transformations. The developed framework
      should be widely applicable in the understanding of perceptual illusions,
      particularly when these are guided by alignment with preferred constructs.
      Secondly, the article reveals the nontrivial mathematical process of perceptual
      semigroup formation and evaluation, deducing the complete description of the
      semigroup constructed in the previous study. Perceptual centering transformations
      identified in terrestrial experiments may predict illusions to be expected in
      spaceflight. For example, our results indicate that under certain conditions,
      many astronauts will misperceive a visual rotation axis to be centered in front
      of the head or even the torso.

PMID- 18626137
TI  - Effect of field of view on the levitation illusion.
AB  - Supine subjects inside a furnished room in which both they and the room are
      pitched 90 degrees backwards may experience themselves and the room as upright
      relative to gravity. This effect is known as the levitation illusion because
      observers report that their arms feel weightless when extended, and objects
      hanging in the room seem to "levitate". This illusion is an extreme example of a
      visually induced illusion of static tilt. Visually induced tilt illusions are
      commonly experienced in wide-screen movie theatres, flight simulators, and
      immersive virtual reality systems. For technical reasons an observer's field of
      view is often constrained in these environments. No studies have documented the
      effect of field-of-view (FOV) restriction on the incidence of the levitation
      illusion. Preliminary findings suggest that when concurrently manipulating the
      FOV and observer position within an environment, the incidence of levitation
      illusions depends not only on the field of view but also on the visible scene
      content.

PMID- 18626138
TI  - Mental own-body and body-part transformations in microgravity.
AB  - The aim of this experiment was to investigate the influence of gravity on the
      cognitive ability to mentally transform images of bodies or body parts. A total
      of eight participants were tested in two separate parabolic flight missions. In
      the main experiment, participants had to make a discrimination judgement (left or
      right) about pictures of a human figure with one arm outstretched, and pictures
      of a body part (hand). The stimuli appeared in varying views and orientations.
      Response times and error rates were measured. In microgravity, the participants
      showed increased response times overall as well as increased error rates when
      compared to 1 g for both types of stimuli. Thus, a task that requires the mental
      transformation of one's own body or body parts becomes more difficult during
      microgravity. This is in contrast to previous studies showing no effect of
      microgravity on the mental rotation of abstract 3D objects and to our follow-up
      case study in which participants applied an object-based mental rotation
      strategy. Moreover, the analysis of response times suggests that in microgravity
      body-part stimuli are affected more strongly than body figures.

PMID- 18626139
TI  - Measurement of oscillopsia induced by vestibular Coriolis stimulation.
AB  - We demonstrate a new method for measuring the time constant of head-movement
      contingent oscillopsia (HMCO) produced by vestibular Coriolis stimulation.
      Subjects briskly rotated their heads around pitch or roll axes whilst seated on a
      platform rotating at constant velocity. This induced a cross-coupled vestibular
      Coriolis illusion. Simultaneous with the head movement, a visual display
      consisting of either a moving field of white dots on a black background or
      superimposed on a subject-stationary horizon, or a complete virtual room with
      conventional furnishings appeared. The scene's motion was driven by a simplified
      computer model of the Coriolis illusion. Subjects either nulled (if visual motion
      was against the illusory body rotation) or matched (if motion was in the same
      direction as the illusory motion) the sensation with the exponentially slowing
      scene motion, by indicating whether its decline was too fast or too slow. The
      model time constant was approximated using a staircase technique. Time constants
      comparable to that of the Coriolis vestibular ocular reflex were obtained. Time
      constants could be significantly reduced by adding subject-stationary visual
      elements. This technique for measuring oscillopsia might be used to quantify
      adaptation to artificial gravity environments. In principle more complex models
      can be used, and applied to other types of oscillopsia such as are experienced by
      BPPV patients or by astronauts returning to Earth.

PMID- 18626140
TI  - Chlorpheniramine and ephedrine in combination for motion sickness.
AB  - BACKGROUND: Chlorpheniramine is effective against motion sickness, but produces
      sedation. To reduce chlorpheniramine's sedating effect and increase its
      effectiveness, ephedrine was combined with chlorpheniramine to prevent motion
      sickness. METHODS: Chlorpheniramine (C) and chlorpheniramine plus ephedrine
      (Chlorphedra) were studied in a randomized, double blind, crossover trial.
      Eighteen normal subjects were randomized to six different orderings of placebo, C
      (12 mg) or Chlorphedra (12 mg C + 50 mg ephedrine). They ingested the medication
      3.25 hours before off vertical axis rotation in a rotating chair. Cognitive
      testing with both objective and subjective tests was performed before drug
      ingestion, at peak drug effect and following rotation. RESULTS: Both C and
      Chlorphedra significantly increased chair time compared to placebo [6.6 to 10.3
      minutes (C), 10.2 minutes (Chlorphedra), p<0.01]. Subjects reported significantly
      more sleepiness on the Karolinska sleepiness scale after taking C (3.3 placebo,
      4.9 C (p<0.005)) but not with Chlorphedra (3.3 placebo, 3.1 Chlorphedra).
      Chlorphedra resulted in significantly higher reported alertness, clearheadedness
      and attentiveness compared to C. Deficits seen on objective tests with C were
      corrected with Chlorphedra. Subjects noted more side effects with Chlorphedra.
      CONCLUSION: Ephedrine does not increase the effectiveness of chlorpheniramine
      against motion sickness, but counteracts sedative and performance effects
      successfully.

PMID- 18626141
TI  - Efficacy of histaminergic drugs in experimental motion sickness.
AB  - The purpose of this investigation was to evaluate the efficacy of the
      histaminergic drug "Betahistine dihydrochloride" in experimental motion sickness
      in 10 healthy volunteers (mean age 19.4 y.o.) with high susceptibility to motion
      sickness. Motion sickness was modeled using Coriolis (precession) accelerations
      (cumulative Coriolis stimulation test--CCST). Each subject took 32 mg of
      "Betahistine dihydrochloride" or placebo under "double-blind" conditions 1 hour
      before testing. The duration and slow phase velocity of the post-rotational
      nystagmus, the pursuit eye tracking test, and the latency, velocity and accuracy
      of saccades were estimated. The tolerability level of the CCST in volunteers in
      the betahistine series was shown to be significantly (p<0.001) higher, as
      compared to placebo and baseline. The mean illusory sensations score for the
      experimental series was significantly lower than that in the placebo and baseline
      series (p < 0.01). It was found that "Betahistine" demonstrated antimotion
      sickness efficacy and improved oculomotor activity (increased gain during pursuit
      movements, faster and more accurate saccades).

PMID- 18626142
TI  - Sickness induced by head movements after different centrifugal Gx-loads and
      durations.
AB  - It has been found that sustained centrifugation on Earth may evoke sickness
      symptoms that are similar to those of the Space Adaptation Syndrome (SAS). As in
      SAS, incidence of this 'Sickness Induced by Centrifugation' (SIC) is about 50%
      and the symptoms are particularly evoked by head movements. By systematically
      varying the G-load and duration of centrifugation, the current study investigated
      the characteristics of the gravitational stimulus that is required for SIC to
      occur. Subjects were exposed to centrifugation at 2 and 3Gx, for a duration of 45
      and 90 minutes. A standardized head movement protocol was used to evoke SIC after
      centrifugation. The results show that in six out of 12 subjects (50%) no serious
      symptoms were elicited. In the remaining subjects, the effects of the 3G runs
      exceeded those of the 2G runs, and within each G-level symptom intensity was
      higher for the 90 min than for the 45 min exposure. An exponential fit on this
      data showed that the time constant of adaptation to the gravitational stimulus
      was about 60 minutes. This suggests that short duration exposures (i.e. <60 min)
      are not likely to induce serious SIC.

PMID- 18626143
TI  - Effect of radius versus rotation speed in artificial gravity.
AB  - Artificial gravity by centrifugation can lead to perceptual disturbances in the
      form of motion sickness and/or misperception of motion during head movements, but
      the degree of perceptual disturbance during centrifugation in 0-g has not been
      thoroughly investigated. It is known that during whole-body on-axis yaw rotation
      in 0-g, head movements in pitch and roll cause very little disturbance, despite
      significant disturbance in 1-g. Therefore, 1-g experimental results do not apply
      directly to 0-g without further analysis. A modeling approach was used here to
      predict disorienting effects in 0-g and 1-g environments, with different rotation
      speeds, centrifuge radii, and directions of head movement. The results were based
      upon investigation of the stimulus itself, in the form of angular and linear
      accelerations, and their consequences due to linear-angular interactions in three
      dimensions. The results explain known differences in 0-g and 1-g, for head turns
      toward and away from the direction of motion, and for head movements on- and off
      axis. Additional predictions include an increase in perceptual disturbance with
      the magnitude of the gravito-inertial acceleration (GIA), therefore an increase
      off-axis, but a decrease in 0-g. Also predicted is that head-movement direction
      makes a difference, with rotation outward relative to the centrifuge axis causing
      the least disturbance.

PMID- 18626144
TI  - Spatial symmetry groups as sensorimotor guidelines.
AB  - While some aspects of neuroanatomical organization are related to packing and
      access rather than to function, other aspects of anatomical/physiological
      organization are directly related to function. The mathematics of symmetry groups
      can be used to determine logical structure in projections and to relate it to
      function. This paper reviews two studies of the symmetry groups of vestibular
      projections that are related to the spatial functions of the vestibular complex,
      including gaze, posture, and movement. These logical structures have been
      determined by finding symmetry groups of two vestibular projections directly from
      physiological and anatomical data. Logical structures in vestibular projections
      are distinct from mapping properties such as the ability to maintain two- and
      three-dimensional coordinate systems; rather, they provide
      anatomical/physiological foundations for these mapping properties. The symmetry
      group of the direct projection from the semicircular canal primary afferents to
      neck motor neurons is that of the cube (O, the octahedral group), which can serve
      as a discrete skeleton for coordinate systems in three-dimensional space. The
      symmetry group of the canal projection from the secondary vestibular afferents to
      the inferior olive and thence to the cerebellar uvula-nodulus is that of the
      square (D8), which can support coordinates for the horizontal plane. While the
      mathematical relationship between these symmetry groups and functions of the
      vestibular complex are clear, these studies open a larger question: what is the
      causal logic by which neural centers and their intrinsic organization affect each
      other and behavior? The relationship of vestibular projection symmetry groups to
      spatial function make them ideal projections for investigating this causal logic.
      The symmetry group results are discussed in relationship to possible ways they
      communicate spatial structure to other neural centers and format spatial
      functions such as body movements. These two projection symmetry groups suggest
      that all vestibular projections may have symmetry groups significantly related to
      function, perhaps all to spatial function.

PMID- 18626145
TI  - Statement on publishing clinical trials in Indian biomedical journals.

PMID- 18626146
TI  - Hairy cell leukemia: clinical, pathological and ultrastructural findings in Asian
      Indians.
AB  - BACKGROUND: Hairy-cell leukemia (HCL), lymphoproliferative disease of older age,
      is characterized by projections from surface of abnormal cells. AIM: The aim was
      to study the clinical presentation and ultrastructural changes in hairy cells
      (HCs) following cladribine treatment. SETTINGS AND DESIGN: Clinical presentation,
      peripheral smear, bone marrow aspiration and biopsy of HCL cases diagnosed over a
      period of three years were reviewed. MATERIALS AND METHODS: Consecutive HCL cases
      in Hematology clinic of a tertiary care center were enrolled. Tartarate-resistant
      acid phosphatase (TRAP) test was done to detect HCs and electron microscopy was
      done to demonstrate initial ultrastructural changes and alterations following
      cladribine therapy. RESULTS: Fifteen cases of HCL, aged 32-57 years (median 47
      years) were studied. The clinical presentation included splenomegaly in 15
      (100%), fever in 10 (67%), hepatomegaly and pain abdomen in eight (53%), fatigue
      in nine (60 %) cases. The commonest laboratory features were monocytopenia in 13
      (87%), neutropenia in 12 (80%), anemia in 10 (67 %) and pancytopenia in nine
      (60%). All patients showed symptomatic improvement on cladribine therapy.
      Electron microscopy after treatment (three months) showed loss of the finger like
      projections, characteristic bald lymphocytes, loss of ribosomal lamellar
      complexes, as well as decrease in mitochondria and vacuoles. CONCLUSIONS: Indian
      patients with HCL are younger. Cladribine is an effective therapy for these
      patients and leads to complete response in most of the patients. There is a
      significant improvement in the ultrastructural features following cladribine
      therapy.

PMID- 18626147
TI  - Bone marrow morphological changes in patients of chronic myeloid leukemia treated
      with imatinib mesylate.
AB  - BACKGROUND: Imatinib mesylate has shown promising results in chronic myeloid
      leukemia (CML) in all phases. This drug is an effective treatment for patients
      with CML in chronic phase as it induces hematological remission in nearly all
      patients and cytogenetic responses in many. The bone marrow changes produced by
      this drug are different from the treatment modalities used earlier in CML.
      MATERIALS & METHODS: We studied 80 patients of CML on treatment with Imatinib at
      doses of 400-800 mg per day. Morphological and cytogenetic evaluation (Ph
      analysis) of bone marrow aspirates was done at six months of treatment. RESULT:
      In our study, 95% (76 out of 80) patients showed complete hematological response
      and 63.3% showed major cytogenetic response at the end of six months of
      treatment. The most commonly observed changes in the bone marrow aspirates at the
      end of six months of therapy were in the form of reduction in the cellularity,
      reduction in the M: E ratio to a mean of 2:1, presence of relative erythroid
      hyperplasia, normalization of megakaryocytic morphology and variable increase in
      the bone marrow lymphocytes. None of these changes had significant correlation
      with the patient's Ph status. CONCLUSION: We advise study of trephine biopsies to
      overcome the often-faced problem of hemodiluted aspirates in these cases and
      evaluation of sequential bone marrows to check the durability of these
      morphological changes and their correlation with the cytogenetic response with
      emphasis on cytogenetic changes other than Ph positivity.

PMID- 18626148
TI  - Mammographic density as a risk factor for breast cancer in a low risk population.
AB  - BACKGROUND: Mammographic density is a function of abundance of epithelial and
      connective tissue in breast. It has been identified as an independent risk factor
      for breast cancer in studies in western populations. We conducted a case control
      study to evaluate the role of mammographic density as risk factor for the
      development of breast cancer in Indian patients. METHODS: One hundred and one
      cases of breast cancer and 123 healthy controls were included in the study.
      Mammographic density of the breast tissue of all controls and the contralateral
      breast of breast cancer patients was measured using a six category scale by a
      qualified radiologist. RESULTS: A low prevalence of dense mammographic patterns
      (16.3% in controls and 26.7% in cases) was seen in the study population.
      Premenopausal women with breast density of 50% or more had 3.8 times risk of
      developing breast cancer than women with breast density of < 10%. (OR = 3.86, 95%
      CI = 1.4-10.1). In postmenopausal women with mammographically dense breast, no
      such increase in risk was noted. CONCLUSION: High mammographic density patterns
      are associated with an increased risk for the development of breast cancer in
      younger women in a low risk population, whereas no such increase in risk is seen
      in postmenopausal women.

PMID- 18626149
TI  - Cervical lymph node metastases of squamous cell carcinoma from an unknown
      primary: outcomes and patterns of failure.
AB  - CONTEXT: Management of cervical lymph nodes metastases of squamous cell carcinoma
      (SCC) from primary of unknown origin (PUO) is contentious and there is
      insignificant data from India on this subject. AIMS: To present experience of
      management of these patients treated with curative intent at a single
      institution. SETTINGS AND DESIGN: Retrospective study of patients treated between
      1989-1994 in a tertiary referral cancer centre. MATERIALS AND METHODS: Eighty
      nine patients were evaluated in the study period and their survival compared with
      patients with common sites of primary in the head and neck with comparable node
      stage. STATISTICAL ANALYSIS USED: Kaplan-Meier method. RESULTS: The clinical
      stage of the neck nodes at presentation was N1 in 11%, N2a in 28.5%, N2b in
      22.5%, N3 in 35% and Nx in 3.4% patients. All patients underwent surgery and 70
      patients received more than 40Gy postoperative radiotherapy. Twenty-nine (32.6%)
      patients had relapse of which 19 (21%) were in the neck. Postoperative
      radiotherapy did not influence the neck relapse (p=0.72). Primary was detected in
      13 patients (14.6%) on subsequent follow up. The overall five and eight-years
      survival was 55% and 51% respectively. The overall five-year survival was better
      compared to patients with known primary with comparable node stage. CONCLUSIONS:
      Patients with cervical lymph nodes metastases of SCC from PUO have reasonable
      survival and low rate of development of subsequent primary when treated with
      surgery and radiotherapy. The overall survival is comparable to that of patients
      with known primary and hence an attempt at cure should always be made.

PMID- 18626150
TI  - Immunoprofile of Hodgkin's lymphoma in India.
AB  - AIMS AND BACKGROUND: The immunoprofile of the Reed Sternberg cell with respect to
      immunoreactivity for CD20 and lack of CD15 has been described as a poor
      prognostic factor. Large scale studies analyzing the immunoprofile of Hodgkin's
      lymphoma (HL) from India are lacking. The aim of this study was to obtain
      baseline information on relative frequencies and immunoprofiles of the two major
      types of HL and comparing reports from developed and developing countries.
      MATERIALS AND METHODS: 451 cases of HL were classified as per the WHO into
      classical (n= 397) HL (cHL) and nodular lymphocyte predominant HL (NLPHL) (n=54).
      Cases of cHL were divided into 5 immunophenotypic groups; Group A
      (CD15+,CD30+,CD20-), Group B (CD15-,CD30+,CD20-), Group C (CD15+,CD30+,CD20+),
      Group D (CD15-,CD30+,CD20+)and Group E (CD15-,CD30-,CD20+). In cases of NLPHL,
      the immunophenotype of lymphocytes in the background, whether T(CD3) or B(CD20)
      rich was observed. RESULTS: Most cases of cHL belonged to Group A (44.58%)
      followed by Group B (40.05%), C(5.54%), D(9.57%) and E(0.25%). Half, (50.89%) the
      cases of cHL were immunonegative for CD15, whereas CD20 was expressed by 15.61%
      of the cases. Three (5.55%) cases of NLPHL showed a CD3 (T) cell rich background.
      Significant differences were also observed with respect to the age distribution
      of cHL as compared to the west. CONCLUSION: Our study demonstrates that India has
      a high number of CD15 negative and a relatively higher number of CD20 positive
      cHL cases as compared to the western population. Favorable treatment response and
      good cure rates that one sees in western cHL may not apply to India.

PMID- 18626151
TI  - Wunderlich's syndrome with hepatic angiomyolipoma in tuberous sclerosis.
AB  - We present a patient of tuberous sclerosis complex with bilateral renal
      angiomyolipoma and hepatic angiomyolipoma with spontaneous retroperitoneal
      hemorrhage from right angiomyolipoma (Wunderlich's syndrome). Nephron preserving
      approach was tried but the right kidney could not be salvaged. Hepatic
      angiomyolipoma was managed conservatively. Wunderlich's syndrome has been found
      in around 10% of cases of renal angiomyolipomas. Hepatic Angiomyolipoma is a
      benign mesenchymal neoplasm of the liver which is rarely reported in literature.

PMID- 18626152
TI  - A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult
      male: a rare case report with review of literature.
AB  - Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such cases have
      dealt with molecular analysis. A 19-year-old boy presented with pain and swelling
      in his left lower limb of two months duration. He developed acute urinary
      retention four days prior to his hospital admission, wherein radiological
      examination unraveled a large soft tissue mass, displacing his pelvic muscles,
      along with a lytic lesion involving his right pubic bone. Biopsy showed a
      cellular spindle cell sarcoma, exhibiting hemangiopericytoma-like vascular
      pattern with focal necrosis. Immunohistochemistry (IHC) showed positivity for
      vimentin, BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane
      antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was positive.
      Diagnosis of a poorly differentiated synovial sarcoma was offered and confirmed
      with a positive t(X; 18) SYT-SSX2 translocation. This case highlights the value
      of molecular analysis in diagnosis of a synovial sarcoma at rare sites,
      especially when IHC results are equivocal and the biopsy material is limited.

PMID- 18626153
TI  - Adult T cell leukemia: a typical case from India.

PMID- 18626154
TI  - Need for the appraisal of uncommon side effects of a commonly prescribed drug-
      Imatinib.

PMID- 18626155
TI  - Primary mediastinal giant teratocarcinoma.

PMID- 18626156
TI  - Meningeal carcinomatosis from pulmonary adenocarcinoma.

PMID- 18626157
TI  - Perspectives on QOL in India.

PMID- 18626158
TI  - Pulmonary artery sarcoma: the hidden truth.

PMID- 18626159
TI  - Observations on the expression of bcg-1 gene in breast tumor and adjacent tissue.

PMID- 18626160
TI  - End of life care: issues and challenges.

PMID- 18626161
TI  - Undergraduate medical students' research in India.

PMID- 18626162
TI  - Temporomandibular joint skeletal morphology in children and adults.

PMID- 18626163
TI  - Comparison of a dipstick enzyme-linked immunosorbent assay with commercial assays
      for detection of Japanese encephalitis virus-specific IgM antibodies.
AB  - BACKGROUND: Japanese encephalitis (JE) is a major public health concern in Asia
      including India. OBJECTIVES: To evaluate an in-house developed dipstick enzyme
      linked immunosorbent assay (ELISA) test vis-a-vis two commercial kits for
      detection of JE virus-specific IgM antibodies. SETTING AND DESIGN: Comparative
      study carried out in Research and Development centre. MATERIALS AND METHODS: A
      total of 136 specimens comprising 84 serum and 52 CSF samples were tested by in
      house dipstick ELISA, Pan-Bio IgM capture ELISA (Pan-Bio, Australia) and JEV CheX
      IgM capture ELISA (XCyton, India). RESULTS: The overall agreement among all three
      tests was found to be 92% with both serum and cerebrospinal fluid (CSF) samples.
      The sensitivity of the dipstick ELISA was found to be 91% with serum and 89% with
      CSF samples respectively. The specificity of the dipstick ELISA with reference to
      both commercial assays was found to be 100% in serum and CSF samples in this
      study. CONCLUSIONS: The in-house dipstick ELISA with its comparable sensitivity
      and specificity can be used as a promising test in field conditions since it is
      simple, rapid and requires no specialized equipment.

PMID- 18626164
TI  - The application of C12 biochip in the diagnosis and monitoring of colorectal
      cancer: systematic evaluation and suggestion for improvement.
AB  - BACKGROUND: The 12 tumor markers' (TMs) biochip diagnostic (C12) system has been
      proven useful in some previous studies but its value for colorectal cancer (CRC)
      only was not systematically investigated. AIMS: To evaluate the value of C12
      system for CRC. SETTINGS AND DESIGN: The associations between TMs and
      clinicopathological characteristics were evaluated. The most relevant TMs, the
      most useful combinations, and the correlations between TM levels were assessed.
      MATERIALS AND METHODS: The TMs detected by the C12 system in the sera of 170
      pathologically confirmed CRC patients were analyzed. One or more TMs higher than
      or equal to reference value were defined as positive. STATISTICAL ANALYSIS: Chi
      square test, Spearman rank correlation test and Receiver-operating characteristic
      (ROC) curves were used for the analysis. RESULTS: The overall positive rate was
      41.76%, and was low in stage 0-I (12.90%). Carcinoembryonic cantigen (CEA) had
      the highest positive rate of 36.47%. The positive rates were significantly
      correlated to clinical stages and lymph node status, but not to age, sex, tumor
      location and pathological types. Any combinations of the five highest positive
      TMs did not have significantly improvements. The levels of three most related TMs
      (CEA, CA19-9, CA242) of CRC had positive correlation with each other. CA242 and
      beta-HCG levels were associated with lymph node metastasis. CONCLUSIONS: C12
      system has some value in advanced CRC, but not in early CRC.

PMID- 18626165
TI  - A comparative study of the skeletal morphology of the temporo-mandibular joint of
      children and adults.
AB  - BACKGROUND: The skeletal morphology of the temporo-mandibular joint (TMJ) is
      constantly remodeled. AIMS AND OBJECTIVES: A comparative study was undertaken to
      determine and characterize the differences in the skeletal morphology of TMJ of
      children and adults. MATERIALS AND METHODS: The study was conducted on 30
      children cadavers and 30 adult volunteers. Parameters that could reflect TMJ
      skeletal morphology were measured with a new technology combining helical
      computed tomography (CT) scan with multi-planar reformation (MPR) imaging.
      RESULTS: Significant differences between children cadavers and adults were found
      in the following parameters (P<0.05): Condylar axis inclination, smallest area of
      condylar neck/largest area of condylar process, inclination of anterior slope in
      inner, middle, and outer one-third of condyle, anteroposterior/mediolateral
      dimension of condyle, length of anterior slope/posterior slope in inner and
      middle one-third of condyle, anteroposterior dimension of condyle/glenoid fossa,
      mediolateral dimension of condyle/glenoid fossa, inclination of anterior slope of
      glenoid fossa, depth of glenoid fossa, and anteroposterior/mediolateral dimension
      of glenoid fossa. CONCLUSION: There are significant differences of TMJ skeletal
      morphology between children and adults.

PMID- 18626166
TI  - Effect of intravenous metoclopramide on intraocular pressure: a prospective,
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Prevention of rise in intraocular pressure (IOP) is essential in
      patients undergoing surgery for perforated eye injuries. Metoclopramide, a
      prokinetic agent, is commonly used to hasten gastric emptying in emergency
      surgeries. AIM: To study the change in IOP after intravenous metoclopramide and
      to study the influence of metoclopramide on change in IOP after succinylcholine
      and tracheal intubation. SETTINGS AND DESIGN: A randomized, double-blind, placebo
      controlled study of 60 patients undergoing non-ophthalmic elective surgery.
      MATERIALS AND METHODS: Sixty American Society of Anesthesiologists (ASA) I adult
      patients were randomly assigned to receive normal saline (Group C) or
      metoclopramide 10 mg (Group M) 30 min before the induction of anesthesia.
      Thiopentone was used for induction and succinylcholine for tracheal intubation.
      Intraocular pressure was measured in both the eyes pre and post drug treatment
      and succinylcholine and tracheal intubation using Perkins applanation tonometer.
      STATISTICAL ANALYSIS: Student's t-test and repeated measures ANOVA were used. A P
      value < 0.05 was considered as significant. RESULTS: Intraocular pressure was
      consistently lower in Group M than in Group C after the test drug, though the
      difference was not statistically significant. Intraocular pressure decreased
      significantly after administration of thiopentone and increased significantly in
      Groups C and M after tracheal intubation (P<0.01). Intraocular pressure was
      comparable between the groups at all the times. CONCLUSIONS: Metoclopramide does
      not cause a clinically significant change in IOP nor does it influence the
      changes in IOP during anesthesia and tracheal intubation. Metoclopramide shows a
      trend towards decrease in IOP, though clinically insignificant. Therefore
      metoclopramide can be used to promote gastric emptying in patients with
      perforated eye injury.

PMID- 18626167
TI  - Emerging extra-intestinal infections with Aeromonas hydrophila in coastal region
      of southern Karnataka.
AB  - BACKGROUND: Aeromonas species are gram-negative rods usually isolated from the
      gastrointestinal tract. They have been occasionally reported as a cause of extra
      intestinal infections such as cellulitis, cholangitis, necrotizing fascitis,
      meningitis, bacteremia, or peritonitis in both immunocompetent and
      immunocompromised patients. AIM: To determine the role and possible pathogenesis
      of Aeromonas in extra-intestinal infections. SETTINGS AND DESIGN: Retrospective
      analysis carried out at Kasturba Hospital Manipal, Karnataka in the months of
      January and February 2007. MATERIALS AND METHODS: Clinical manifestations and
      management of eight cases of extra-intestinal infections caused by A. hydrophila
      , from the south Karnataka coastal region were reviewed. The isolates were
      identified with the help of biochemical tests using standard guidelines. RESULTS:
      All patients acquired Aeromonas infections in the community. Five (62.5%) had
      underlying illnesses, such as liver disease, diabetes mellitus or malignancy.
      Five (62.5%) had polymicrobial infections, and three (37.5%) were complicated
      with bacteremia. These included three patients with ulcers or abscess over the
      lower leg, two with cellulitis due to snake bite and one each with pelvic
      inflammatory disease, spontaneous bacterial peritonitis and pneumonia. A.
      hydrophila was found to be a causative agent of pelvic inflammatory disease or
      cellulitis following sea snake bite, and such a clinical scenario has not been
      previously described. Seven patients survived the illness. CONCLUSIONS: Isolation
      of A. hydrophila from extra-intestinal specimens demands utmost clinical and
      microbiological vigilance in diagnosis, since the organism can cause serious
      infections among immunocompromised as well as immunocompetent individuals.

PMID- 18626168
TI  - Fungal encephalitis following bone marrow transplantation: clinical findings and
      prognosis.
AB  - BACKGROUND: Central nervous system fungal infections (FI) are important
      complications and a cause of mortality in patients who receive hematopoietic stem
      cell transplantation (HSCT). AIMS: To study the clinical aspects of fungal
      encephalitis (FE). SETTINGS AND DESIGN: The study was carried out at the HSCT
      Center of the Hospital de Clinicas, Federal University of Parana, Curitiba,
      Brazil. MATERIALS AND METHODS: Clinical records and autopsy reports from patients
      submitted to HSCT with a diagnosis of FE. RESULTS: Twelve patients were diagnosed
      with FE presenting with lowered level of consciousness, hemiparesis and seizures.
      We were able to identify two subgroups regarding susceptibility to FE: (1)
      patients with early onset FI and severe leucopenia, and (2) patients with later
      onset FI with graft-versus-host disease using immunosuppressive drugs. Eleven of
      the patients died directly due to the neurological complication, all had post
      mortem confirmation of the diagnosis of FI. CONCLUSIONS: These clinical,
      paraclinical and temporal patterns may provide the opportunity for earlier
      diagnosis and interventions.

PMID- 18626169
TI  - Recurrence of primary hyperoxaluria: an avoidable catastrophe following kidney
      transplant.
AB  - Primary hyperoxaluria is a rare autosomal recessive disease due to deficiency of
      an oxalate-metabolizing liver enzyme, which results in nephrolithiasis and renal
      failure. Concomitant liver and kidney transplant is recommended as isolated
      kidney transplant is inevitably complicated by recurrence of the disease. We
      present a 25-year-old man with end-stage nephrolithiatic renal disease who
      underwent bilateral nephrectomy, followed by kidney transplantation. There was
      progressive worsening of kidney function two weeks post transplant. Review of
      nephrectomy and transplant kidney biopsy showed abundant calcium oxalate crystals
      and further workup revealed hyperoxaluria, which was previously unsuspected.
      Later he developed fever, breathlessness, hemiparesis and died 10 weeks after
      transplant. Autopsy revealed multi-organ deposits of oxalate crystals as well as
      widespread zygomycosis. This case emphasizes the need for careful pre-transplant
      evaluation of patients with renal calculus disease in order to exclude primary
      hyperoxaluria.

PMID- 18626170
TI  - Massive upper GI bleeding: a rare complication of Zenker's diverticulum.
AB  - Bleeding from a Zenker's diverticulum is rare. A 71-year-old man was urgently
      admitted with massive hematemesis. It was known that he had a Zenker's
      diverticulum, but on emergency endoscopy, the source of bleeding was not detected
      due to large blood clots in the esophagus, hypo-pharynx and also into the
      tracheal-bronchial tree. Computerized tomography angiography demonstrated a blush
      of intravenous contrast arising from the diverticulum. The patient was operated
      upon urgently; the diverticle had a deep ulceration which was the source of the
      bleeding. The cause of the ulceration is unknown but it is possible that it was
      caused by the direct effect of an aspirin pill within the diverticle. A similar
      case with the same conclusion has been published in the past and since the use of
      aspirin has become common, especially in the elder population, we present this
      case report to highlight this possible life-threatening complication of Zenker's
      diverticulum in patients receiving aspirin.

PMID- 18626171
TI  - Primary gastrointestinal mucormycosis in an immunocompetent person.
AB  - In the past decade, mucormycosis has emerged as an important lethal infection in
      diabetics and other immunocompromised hosts. Rhinosinusitis, pansinusitis, rhino
      orbital and rhinocerebral are the common classical manifestations of
      mucormycosis. However, primary gastrointestinal (GI) mucormycosis is an uncommon
      disease associated with a high mortality rate. Stomach is the most common site
      involved in GI mucormycosis. Reported cases of GI mucormycosis in an
      immunocompetent host are very few in the literature. Here we present a case of a
      young male with fungal sepsis secondary to GI mucormycosis in an immunocompetent
      person.

PMID- 18626172
TI  - A trial design that generates only ''positive'' results.
AB  - In this article, we test the hypothesis that randomized clinical trials of
      acupuncture for pain with certain design features (A + B versus B) are likely to
      generate false positive results. Based on electronic searches in six databases,
      13 studies were found that met our inclusion criteria. They all suggested that
      acupuncture is effected (one only showing a positive trend, all others had
      significant results). We conclude that the 'A + B versus B' design is prone to
      false positive results and discuss the design features that might prevent or
      exacerbate this problem.

PMID- 18626173
TI  - Promotional literature: how do we critically appraise?
AB  - There has been a tremendous increase in the number of new and generic drugs
      coming into the market. The busy practitioner obtains the information from
      various sources, of which promotional literature forms an important source. The
      promotional literature provided by the pharmaceutical companies cannot be
      entirely relied upon; moreover, very few physicians are equipped with the skills
      of critically appraising it. The new drug should be relevant to the clinician's
      practice in terms of population studied, the disease and the need for new
      treatment. The methodology of the study should be carefully judged to determine
      the authenticity of the evidence. The new drug should be preferred over the
      existing one if it offers clear advantages in terms of safety, tolerability,
      efficacy and price. Critical appraisal of promotional literature can provide
      valuable information to the busy physician to practice evidence-based medicine.

PMID- 18626174
TI  - Story of heparin recall: what India can do?

PMID- 18626175
TI  - A young lady with hypotension and engorged neck veins.

PMID- 18626176
TI  - Electroconvulsive therapy and electrocardiograph changes.

PMID- 18626177
TI  - Benign nevus inclusions in a node with primary squamous carcinoma of tongue.

PMID- 18626178
TI  - Needlestick injury to a patient.

PMID- 18626179
TI  - Gatifloxacin-induced rhabdomyolysis.

PMID- 18626180
TI  - L-tryptophan and scleroderma: significance of nutritional supplements containing
      L-tryptophan.

PMID- 18626181
TI  - Symptomatic hypocalcemia following intravenous administration of zoledronic acid
      in a breast cancer patient.

PMID- 18626182
TI  - Kayser-Fleischer ring.
AB  - Kayser-Fleischer (K-F) ring seen in Wilson's disease (WD) is due to copper
      deposition in the Descemet's membrane in the sclero-corneal junction. Although
      believed to be pathognomic of WD, it may be seen in many other hepatic conditions
      and intraocular copper-containing foreign bodies. The K-F ring detected in pre
      symptomatic cases of WD may lead to speedy diagnosis and early management. Co
      relation of K-F ring in WD to the disease severity, disappearance with successful
      treatment, reappearance with non-compliant treatment may aid in optimum
      management of WD. The importance of K-F ring detection in first-degree relatives
      of the index case cannot be over-emphasized.

PMID- 18626183
TI  - Stavudine-induced pancreatitis followed by lopinavir-ritonavir-induced
      pancreatitis: is co-trimoxazole the culprit?

PMID- 18626184
TI  - Automated blood counts and identification of thalassemia carriers.

PMID- 18626185
TI  - Nimesulide and adverse drug reactions: time for a database.

PMID- 18626186
TI  - Catatonic stupor in a case of pontine and extrapontine myelinolysis: clinical and
      radiological dissociation.

PMID- 18626187
TI  - Hand contracture: an unusual sequel of intravenous fluid extravasation in the
      neonatal period.

PMID- 18626188
TI  - Low-dose inhaled versus standard dose oral form of anti-tubercular drugs:
      concentrations in bronchial epithelial lining fluid, alveolar macrophage and
      serum.

PMID- 18626189
TI  - Developmental perspectives on individual variation: implications for
      understanding nutritional needs.
AB  - Genetic research has focused on identifying linkages between polymorphisms and
      phenotypic traits to explain variations in complex biologies. However, the
      magnitude of these linkages has not been particularly high. Conversely, the
      ability of developmental plasticity to generate biological variation from one
      genotype is well understood, while interest has emerged in the clinical
      significance of epigenetic processes, particularly those influenced by the
      external environment. Environmental cues in early development may induce
      responses that provide adaptive advantage later in life. The benefit of such
      responses depends on the fidelity of the prediction of the future environment.
      Life history and physiological changes mediated through epigenetic processes then
      follow, determining the later phenotype. Developmental mismatch, leading to
      disease, can arise from discordance between the fetal environment, which is
      relatively constant across generations, and the postnatal nutritional
      environment, which can change drastically within and between generations.
      Metabolic disorders represent the outcome of an individual living in an
      energetically inappropriate environment. Experimental and clinical evidence
      suggests that individual capacity to live in a given energetic environment is
      influenced by developmental factors acting through epigenetic mechanisms.
      Epigenetic biomarkers may be able to identify a risk of developmental mismatch
      and thus offer the opportunity for nutritional or other intervention.

PMID- 18626190
TI  - Factors influencing the establishment of the intestinal microbiota in infancy.
AB  - The establishment of the intestinal microbiota commences at birth and new
      bacteria establish in succession during the first years of life until an adult
      type highly complex microbiota has been achieved. The first bacteria to establish
      in the neonatal gut are usually aerobic or facultatively anaerobic bacteria, like
      enterobacteria, enterococci and staphylococci. During their growth they consume
      oxygen and change the intestinal milieu making it suitable for the proliferation
      of anaerobic bacteria. Bifidobacterium, Clostridium and Bacteroides are among the
      first anaerobes establishing in the microbiota. As more oxygen-sensitive species
      establish and the complexity of the microbiota increases, the population sizes of
      aerobic and facultative bacteria decline. This phenomenon is thought to result
      from oxygen depletion, substrate competition and the accumulation of toxic
      metabolites. A wide range of factors influence the intestinal microbiota and its
      establishment, including delivery and feeding mode, antibiotic treatment, and
      contacts with parents, siblings, and hospital staff. Differences in colonization
      pattern can be observed between vaginally and sectiodelivered infants, and
      between infants in industrialized and developing countries, reflecting the
      importance of maternal microbiota and the environment as sources of colonizing
      bacteria. This article describes the intestinal colonization pattern in human
      infants, and reviews factors affecting this process.

PMID- 18626191
TI  - Genetically determined variation in polyunsaturated fatty acid metabolism may
      result in different dietary requirements.
AB  - Tissue availability of polyunsaturated fatty acids (PUFAs) is of major relevance
      for health, and it depends on both dietary intake and metabolic turnover. We
      found close associations between variants in the human genes of Delta5- and
      Delta6-desaturase, FADS1 and FADS2, and serum phospholipid contents of PUFAs and
      long-chain PUFAs (LCPUFAs). Polymorphisms and reconstructed haplotypes of FADS1
      and the upstream region of FADS2 showed strong associations with levels of the n
      6 LC-PUFA arachidonic acid (20:4n-6). Carriers of the less common polymorphisms
      and their respective haplotypes also had a lower prevalence of allergic rhinitis
      and atopic eczema. Our data demonstrate for the first time that the fatty acid
      composition of serum phospholipids is genetically controlled by the FADS1 FADS2
      gene cluster. The investigated single nucleotide polymorphisms in this cluster
      explain 28% of the variance of serum phospholipid arachidonic acid and up to 12%
      of its precursor acids. Based on this genetic variation, individuals may require
      different amounts of dietary PUFAs or LC-PUFAs to achieve comparable biological
      effects. We strongly recommend including analyses of FADS1 and FADS2 polymorphism
      in future cohort and intervention studies addressing the biological effects of
      PUFAs and LC-PUFAs, which should enhance the sensitivity and precision of such
      studies.

PMID- 18626192
TI  - Discussion on '(molecular) imaging: developments enabling evidence-based
      medicine'.

PMID- 18626193
TI  - Metabolic profiling.
AB  - The concept of chemical individuality was introduced by Garrod in 1908.
      Inheritance of Mendelian traits including disease states has finally reached a
      new level of understanding based on the modern principles of gene expression
      coupled with new insight into the metabolism of RNA species and protein. Over 300
      different perturbations in metabolite profiles with their identifying
      alteration(s) in protein and/or gene structure and/or function have been
      identified in the past 100 years. With the realization in 1953 that the sentinel
      disease, phenylketonuria, can be effectively treated by nutritional manipulation
      tailored to the needs of each individual, we have essentially entered a new phase
      in metabolic medicine, namely that of nutritional therapeutics. The infant
      destined for a lifetime of cognitive and motoric handicaps may be rescued by the
      implementation of a nutritional prescription in early development. Patients with
      inherited defects that impact on intermediary metabolism need to receive
      nutritional therapy on an individualized basis. Metabolic profiling, i.e., the
      array of small molecules or analytes, as well as large macromolecules, measured
      with precision in body fluids or tissues, can be used to devise a nutritional
      therapeutic plan, as well as serve as endpoints to evaluate the biochemical
      efficacy of intervention.

PMID- 18626194
TI  - Newborn screening of metabolic disorders: recent progress and future
      developments.
AB  - Tandem mass spectrometry has been the main driver behind a significant expansion
      in newborn screening programs. The ability to detect more than 40 conditions by a
      single test underscores the need to better understand the clinical and laboratory
      characteristics of the conditions being tested, and the complexity of pattern
      recognition and differential diagnoses of one or more elevated markers. The panel
      of conditions recommended by the American College of Medical Genetics, including
      20 primary conditions and 22 secondary targets that are detectable by tandem mass
      spectrometry has been adopted as the standard of care in the vast majority of US
      states. The evolution of newborn screening is far from being idle as a large
      number of infectious, genetic, and metabolic conditions are currently under
      investigation at variable stages of test development and clinical validation. In
      the US, a formal process with oversight by the Advisory Committee on Heritable
      Disorders and Genetic Diseases in Newborns and Children has been established for
      nomination and evidence-based review of new candidate conditions. If approved,
      these conditions could be added to the uniform panel and consequently pave the
      way to large scale implementation.

PMID- 18626195
TI  - The phenotype of human obesity: the scope of the problem.
AB  - The prevention and treatment of childhood obesity have proven to be extremely
      difficult problems. Since the equation for maintaining energy balance is an
      extremely simple one, having only two terms, 'energy in' and 'energy out', the
      difficulties encountered in its application for obesity management are not
      immediately obvious. Among the problems that make practical application of the
      energy balance equation more difficult than expected are: (1) the precise
      feedback control system that is designed to maintain weight within a given range;
      (2) the aggressive resistance of the system to attempts to exceed its boundaries;
      (3) inaccurate assessment of energy intake in practice; (4) the dominant role of
      genes in determining body weight; (5) the polygenic nature of obesity and the
      fact that any single gene accounts for a small fraction of the genetic variation
      in weight; (6) underestimation of the genetic contribution to the current
      'epidemic' of obesity; (7) the fact that 'modifiable' risk factors may be less
      modifiable than expected; (8) appreciation that family role modeling may be less
      influential than anticipated, and (9) the realization that our knowledge about
      the development of physical activity behaviors in childhood is extremely limited.

PMID- 18626196
TI  - Intestinal immune health.
AB  - The fetal intestinal immune system is structurally intact from a very early
      gestational age. At birth, the neonate is challenged with an extraordinary and
      variable bacterial challenge. This mucosal and bacterial interface is the site of
      critical symbiotic and potentially pathogenic interactions. Neonatal inflammatory
      reactions are often exaggerated, creating a situation in a newly colonized gut
      whereby homeostasis must be actively achieved. Fortunately, the neonate is armed
      with a multitude of protective mechanisms by which to ensure a productive
      microbiota in the setting of an intact mucosal surface. The intestinal epithelium
      orchestrates complex interactions and signaling through a variety of intrinsic
      and extrinsic stimuli. Chief among these is the immunomodulatory capacity of
      breast milk which is increasingly implicated in the achievement of intestinal and
      immunologic health via a multitude of mechanisms. Additionally, developmental
      expression of enzymes, pattern recognition, downstream signaling and dendritic
      cell interaction all contribute to intestinal homeostasis. Current research is
      uncovering the molecular mechanisms behind many of these mechanisms. These
      strategies lend insight into the establishment of tolerance so critical to
      neonatal health. In a clinic context of increasing food allergy and inflammatory
      bowel disease, elucidating this machinery is increasingly pertinent. Future
      research should explore these molecular interactions more closely for their
      potential therapeutic applications.

PMID- 18626197
TI  - Gut decontamination with norfloxacin and ampicillin enhances insulin sensitivity
      in mice.
AB  - Recent data suggest that gut microbiota plays a significant role in fat
      accumulation. However, it is not clear whether gut microbiota is involved in the
      pathophysiology of type-2 diabetes. To address this issue, we modulated gut
      microbiota with two combinations of antibiotics in two different mouse models
      with insulin resistance. Treatment with norfloxacin and ampicillin for 2 weeks
      reduced the cecal bacterial DNA below the level of detection in ob/ob, diet
      induced obese and insulin resistance (DIO) mice, and significantly improved
      fasting glycemia and oral glucose tolerance of the treated animals. The enhanced
      insulin sensitivity was independent of food intake or adiposity because pair-fed
      ob/ob mice were as glucose intolerant as the untreated ob/ob mice. The reduced
      liver triglycerides, increased liver glycogen and improved glucose tolerance in
      the treated mice indicate broad impacts on metabolism by gut decontamination. The
      treatment with non-absorbable antibiotics polymyxin B and neomycin significantly
      modified cecal microbiota profile in the DIO mice, and the modified intestinal
      microbiota was associated with a gradual reduction in glycemia during a washout
      period. In summary, modulation of gut microbiota ameliorated glucose intolerance
      in mice and altered the hormonal, inflammatory and metabolic status of the host.

PMID- 18626198
TI  - Individual epigenetic variation: when, why, and so what?
AB  - Epigenetics provides a potential explanation for how environmental factors modify
      the risk for common diseases among individuals. Interindividual variation in DNA
      methylation and epigenetic regulation has been reported at specific genomic
      regions including transposable elements, genomically imprinted genes and the
      'inactive' X chromosomes in females. We currently have a very poor understanding
      of the factors that contribute to interindividual epigenetic variation. In
      particular, it is important to understand when during the life cycle epigenetic
      variation arises, why epigenetic regulation varies among individuals, and whether
      epigenetic interindividuality affects susceptibility to diet-related chronic
      disease. In this review we will summarize current progress toward answering these
      questions.

PMID- 18626199
TI  - Interaction of early infant feeding, heredity and other environmental factors as
      determinants in the development of allergy and sensitization.
AB  - The role of early infant nutrition in the development of allergic symptoms and
      allergic sensitization has been disputed for 70 years. Interaction between
      genetic factors and infant feeding has been limited to studies on parental
      heredity of allergy and length of breastfeeding, as well as the qualities of
      breast milk. In the 10 original studies comparing the development of allergic
      symptoms among children in whom breastfeeding duration was used as a risk factor
      separately among those with either positive or negative parental heredity for
      atopy, no definite answer could be found. The effect of early feeding was even
      changed in both heredity negative and positive groups when looking at symptoms at
      ages 2 and 5 years. Of 9 possible combinations, 6 were present in the studies,
      and none in more than 2 studies. For sensitization, long breastfeeding was a risk
      in 3 of 5 reports if the family history of allergy was positive, and in 2 if
      negative. Low levels of soluble CD14 and cow's milk-specific IgA antibodies in
      breast milk may increase an infant's risk of developing allergy.

PMID- 18626200
TI  - Personalized care of pediatric cancer patients.
AB  - One of the great success stories of clinical oncology is the improvement in the
      cure rates of pediatric acute lymphoblastic leukemia (ALL) from around 10% in the
      1960s to nearly 90% today. The primary factor responsible for this remarkable
      improvement is the personalization of treatment, with stratification of patients
      based on both disease and host characteristics in order to optimize therapy.
      While age, WBC, and immunophenotype provide a rudimentary system for
      classification of ALL, molecular factors are playing an increasingly important
      role in further individualization of ALL therapy. Such risk-based stratification
      strategies are also increasingly being used in the treatment of children with
      solid tumors. In addition, genomic technologies are now being used to identify
      new molecular markers or signatures for both diagnostic and prognostic purposes.
      Recently we reported the analysis of pediatric osteosarcoma by expression
      profiling in an attempt to identify a molecular signature that could predict the
      chemoresistance of a tumor before treatment is initiated. We identified a 45-gene
      signature that discriminates between good and poor responders to chemotherapy in
      osteosarcoma. Using this classifier, we can predict with 100% accuracy the
      chemoresponse of osteosarcoma patients prior to the initiation of treatment.
      These encouraging results suggest that the genomic approach will revolutionize
      the diagnosis and prognosis of pediatric cancer patients and improve their
      outcome through predictive, personalized care.

PMID- 18626201
TI  - Personalizing nutrient intakes of formula-fed infants: breast milk as a model.
AB  - The growth pattern of formula-fed infants is quite different from that of
      breastfed infants. There may be several reasons for this difference, ranging from
      different endocrine responses to feeding and the presence of growth factors in
      breast milk to different control of food intake, but it is highly likely that
      differences in nutrient composition of the food (breast milk or formula) have
      major effects on growth. In most countries infant formula is used more or less
      exclusively up to 6 months of age and as part of the diet up to 12 months of age
      and during this period its composition remains the same. In striking contrast,
      the nutrient composition of breast milk changes during lactation, most
      dramatically during early lactation, but with pronounced differences throughout
      lactation for many nutrients. It is a goal that the performance of formulafed
      infants should be as similar to that of breastfed infants as possible, and
      attempts have been made to modify the composition of infant formula to achieve
      this goal. However, there has been no systematic attempt to gradually change the
      composition of infant formula in a manner similar to the changing pattern of
      breast milk. This represents a technical and nutritional challenge, but is now
      possible.

PMID- 18626203
TI  - Opportunities for improving the health and nutrition of the human infant by
      probiotics.
AB  - The newborn is first colonized by microbes at birth. The colonizing bacteria
      originate mainly from the mother's gut, vaginal tract and skin. The origin of the
      microbiota and its development depend on genetics, mode of delivery, early
      feeding strategies and the hygienic conditions around the child. The indigenous
      microbiota of an infant's gastrointestinal tract is modulated through contact and
      interaction with the microbiota of the parents and the infant's immediate
      environment. After delivery breastfeeding continues to enhance the original
      inoculum by specific lactic acid bacteria and bifidobacteria and bacteria from
      the mother's skin enabling the infant gut microbiota to be dominated by
      bifidobacteria. These bacteria set the basis for gut microbiotia development and
      modulation along with breastfeeding and the environmental exposures such as
      antibiotic administration. Modifying this exposure can take place by probiotic
      bacteria when breastfeeding is not possible. Thus, incorporating specific
      probiotics selected for the development of the infant's gut microbiota may form a
      beneficial possibility for future infant feeding purposes. Many current
      probiotics have documented strain-specific health-promoting effects, and most of
      the effects that have been demonstrated in infants and children. The target in
      infants is to modify the gut microbiota to resemble that of the healthy breastfed
      infant and to counteract deviations or aberrancies present in infants at risk of
      specific diseases. Thus, providing specific selected probiotics to the mother to
      balance the intestinal microbiota during pregnancy and to the infant after birth.
      As the disturbed succession during early infancy has been linked to the risk of
      developing infectious, inflammatory and allergic diseases later in life, it is
      still of great interest to further characterize both the composition and
      succession of microbiota during infancy. With new methodologies we have been able
      to identify more specific aberrancies in microbiota prior to or during different
      disease states.

PMID- 18626202
TI  - Human milk oligosaccharides: evolution, structures and bioselectivity as
      substrates for intestinal bacteria.
AB  - Human milk contains a high concentration of diverse soluble oligosaccharides,
      carbohydrate polymers formed from a small number of monosaccharides. Novel
      methods combining liquid chromatography with high resolution mass spectrometry
      have identified approximately 200 unique oligosaccharides structures varying from
      3 to 22 sugars. The increasing complexity of oligosaccharides follows the general
      pattern of mammalian evolution though the concentration and diversity of these
      structures in homo sapiens are strikingly. There is also diversity among human
      mothers in oligosaccharides. Milks from randomly selected mothers contain as few
      as 23 and as many as 130 different oligosaccharides. The functional implications
      of this diversity are not known. Despite the role of milk to serve as a sole
      nutrient source for mammalian infants, the oligosaccharides in milk are not
      digestible by human infants. This apparent paradox raises questions about the
      functions of these oligosaccharides and how their diverse molecular structures
      affect their functions. The nutritional function most attributed to milk
      oligosaccharides is to serve as prebiotics - a form of indigestible carbohydrate
      that is selectively fermented by desirable gut microflora. This function was
      tested by purifying human milk oligosaccharides and providing these as the sole
      carbon source to various intestinal bacteria. Indeed, the selectively of
      providing the complex mixture of oligosaccharides pooled from human milk samples
      is remarkable. Among a variety of Bifidobacteria tested only Bifidobacteria
      longum biovar infantis was able to grow extensively on human milk
      oligosaccharides as sole carbon source. The genomic sequence of this strain
      revealed approximately 700 genes that are unique to infantis, including a variety
      of co-regulated glycosidases, relative to other Bifidobacteria, implying a co
      evolution of human milk oligosaccharides and the genetic capability of select
      intestinal bacteria to utilize them. The goal of ongoing research is to assign
      specific functions to the combined oligosaccharide-bacteria-host interactions
      that emerged from this evolutionary pressure.

PMID- 18626204
TI  - Do we need personalized recommendations for infants at risk of developing
      disease?
AB  - Current nutrition recommendations, directed towards populations, are based on
      estimated average nutrient requirements for a target population and intend to
      meet the needs of most individuals within that population. They also aim at
      preventing common diseases such as obesity, diabetes and cardiovascular disease.
      For infants with specific genetic polymorphisms, e.g. some inborn errors of
      metabolism, adherence to current recommendations will cause disease symptoms and
      they need personalized nutrition recommendations. Some other monogenic
      polymorphisms, e.g. adult hypolactasia, are common but with varying prevalence
      between ethnic groups and within populations. Ages at onset as well as the degree
      of the resulting lactose intolerance also vary, making population-based as well
      as personalized recommendations difficult. The tolerable intake is best set by
      each individual based on symptoms. For polygenetic diseases such as celiac
      disease, type-1 diabetes and allergic disease, current knowledge is insufficient
      to suggest personalized recommendations aiming at primary prevention for all high
      risk infants, although it may be justified to provide such recommendations on an
      individual level should the parents ask for them. New technologies such as
      nutrigenetics and nutrigenomics are promising tools with which current nutrition
      recommendations can possibly be refined and the potential of individualized
      nutrition be explored. It seems likely that in the future it will be possible to
      offer more subgroups within a population personalized recommendations.

PMID- 18626205
TI  - [The role of tissue Doppler echocardiography in the evaluation of functional
      capacity of patients with heart failure].
AB  - OBJECTIVES: We investigated correlations between the New York Heart Association
      (NYHA) functional classification system, which is commonly used to assess
      functional capacity, and conventional echocardiographic and tissue Doppler
      echocardiographic (TDE) parameters in patients with heart failure (HF). STUDY
      DESIGN: The study included 122 patients (31 females, 91 males; mean age 59+/-11
      years) with HF, whose left ventricular (LV) ejection fraction (EF) was less than
      50%. The patients were evaluated in two groups based on the NYHA class I-II
      (n=79; mean age 58 years) and class III-IV (n=43; mean age 61 years).
      Correlations were sought between the functional status and standard two
      dimensional echocardiographic and TDE parameters. RESULTS: The NYHA class showed
      significant inverse correlations with LV EF, LV stroke volume, mitral
      deceleration time of early filling, and flow propagation velocity (Vp), and
      significant positive correlations with end-systolic and end-diastolic diameters
      and volumes, pulmonary artery pressure (PAP), and the E/Vp ratio. Mitral early
      (E) and late (A) diastolic peak velocities and the E/A ratio were not correlated.
      Concerning TDE parameters, the NYHA class was in significant inverse correlation
      with systolic (Sm), early (Em) and late (Am) diastolic myocardial velocities, and
      in positive correlation with the E/Em ratio, whereas no correlation was found
      with the Em/Am ratio. Linear regression analysis showed that Sm, EF, and PAP were
      independent variables of functional capacity (beta =-0.33, p<0.005; beta =-0.26,
      p<0.05; beta =0.23, p<0.05, respectively). CONCLUSION: There is significant
      relationship between myocardial velocities and functional capacity, and Sm, in
      particular, has the strongest association compared to conventional
      echocardiographic and other TDE parameters.

PMID- 18626206
TI  - [The effect of plasma asymmetric dimethylarginine (ADMA) level and L
      arginine/ADMA ratio on the development of coronary collaterals].
AB  - OBJECTIVES: It has been shown that asymmetric dimethylarginine (ADMA), an
      endogenous competitive antagonist of nitric oxide (NO) synthase, inhibits
      angiogenesis by reducing the production and bioavailability of NO. We
      investigated the effect of plasma ADMA level and L-arginine/ADMA ratio on the
      development of coronary collateral arteries. STUDY DESIGN: The study consisted of
      94 patients (66 males, 28 females; mean age 59+/-11 years) who underwent coronary
      angiography for suspected coronary artery disease and were found to have severe
      stenosis (>95%) in at least one major coronary artery. The patients were
      evaluated in two groups with poor (Rentrop score 0-1, n=44) and good (score 2-3,
      n=50) coronary collateral circulation according to the Rentrop collateral scoring
      system. Plasma levels of ADMA and L-arginine were measured by high-performance
      liquid chromatography. RESULTS: The two groups were similar with regard to basal
      characteristics and cardiovascular risk factors (p>0.05) except for stable
      angina, which was more common in patients with Rentrop score 2-3 collateral
      circulation (p<0.001). Despite similar L-arginine levels (p>0.05), patients with
      Rentrop score 0-1 had a significantly higher ADMA level (p=0.003) and lower L
      arginine/ADMA ratio (p=0.019). Multivariate logistic regression analysis showed
      that plasma ADMA concentration was an independent predictor of coronary
      collateral development (odds ratio=0.674; 95% confidence interval=0.508-0.894;
      p=0.006). CONCLUSION: Elevated plasma ADMA concentrations are associated with a
      poorly developed coronary collateral circulation, suggesting that dysregulation
      of the NO synthase pathway may result in impaired collateral development.

PMID- 18626207
TI  - Factors associated with prolonged prehospital delay in patients with acute
      myocardial infarction.
AB  - OBJECTIVES: We investigated factors associated with prolonged prehospital delay
      in patients with acute myocardial infarction (AMI). STUDY DESIGN: A total of 439
      patients (351 males, 88 females; mean age 57+/-12 years) with ST-elevation AMI
      were interviewed within 48 hours of hospitalization. Patients were pain-free and
      hemodynamically stable at the time of interview. Data were collected on the time
      from the onset of chest pain to hospital admission and on sociodemographic and
      clinical characteristics. The patients were evaluated in two groups according to
      the place to which the first presentation was made, i.e., a local clinic/small
      hospital (clinic group: n=209, 47.6%) or our tertiary fully equipped
      cardiovascular center (hospital group: n=230, 52.4%). RESULTS: The median and
      mean delay times were 70 min and 185.2+/-334.8 min, respectively. Of the study
      group, 136 patients (31%) arrived within 60 minutes after the onset of symptoms.
      The median delay time was significantly longer in the clinic group (120 min vs 60
      min; p<0.001). Female sex, age > or = 55 years, and total education time <9 years
      were associated with a longer prehospital delay, whereas a history of coronary
      artery disease (CAD), smoking, and the absence of diabetes were associated with a
      shorter prehospital delay. In multivariate regression analysis, total education
      time <9 years, female sex, age > or = 55 years, and the absence of previous CAD
      were independent predictors of prolonged prehospital delay. The incidence of
      direct hospital presentation significantly increased with older age, smoking,
      aspirin use, and previous CAD. In multivariate analysis, only previous CAD was an
      independent predictor of direct hospital presentation. CONCLUSION: The median
      delay time of 70 min in this Turkish cohort is in accordance with the data from
      western populations. Public education campaigns to shorten prehospital delay
      should place more emphasis on the factors and patient subgroups associated with
      prolonged prehospital delay.

PMID- 18626208
TI  - Our experience with transradial approach for coronary angiography.
AB  - OBJECTIVES: Transradial approach (TRA) for coronary angiography has only become
      popular in our country in recent years. In this study, we evaluated radial and
      femoral angiographies performed at our center. STUDY DESIGN: A total of 487
      patients (351 males, 136 females) were scheduled for coronary angiography using
      TRA in 2007. Data regarding the procedure were compared with those of 500
      patients (369 males, 131 females) who underwent coronary angiography via the
      transfemoral approach (TFA). All the procedures were performed by the same
      experienced cardiologist. Coronary angiography from the radial artery was
      performed after a positive Allen test and a careful physical examination of the
      access site. A 100-cm Optitorque radial catheter was mostly used to cannulate
      both right and left coronary arteries. Transfemoral catheterization was performed
      using 6 Fr diagnostic catheters, usually Judkins curve catheters. RESULTS:
      Procedural success rates were 96.5% (n=470) and 98.4% (n=492) in the TRA and TFA
      groups, respectively (p>0.05). The two groups were similar with respect to the
      procedural variables, except for the access time which was slightly higher in the
      TRA group (p<0.01). A higher incidence of coronary slow flow was detected in the
      TRA group (p<0.01). In 423 patients (90.0%), a single catheter was used for both
      selective right and left coronary angiography in the TRA group, resulting in a
      significantly lower number of catheter use (2.1+/-0.2 vs 3.2+/- 03; p<0.001).
      Only minor complications were seen during TRA, most commonly being pain and
      ecchymoses. In the TFA group, 27 patients (5.4%) developed hematoma at the access
      site, of more than 5 cm in diameter. Hospital stay was significantly shorter in
      the TRA group (2.1+/-0.4 hr vs 6.7+/-1.0 hr; p<0.001). CONCLUSION: Transradial
      coronary angiography is a good alternative to TFA and can be performed safely and
      effectively in eligible patients.

PMID- 18626209
TI  - [Evaluation of surgical approaches and early and midterm results of treatment for
      atrioventricular septal defect].
AB  - OBJECTIVES: We evaluated patients who underwent complete or partial surgical
      correction for atrioventricular septal defect (AVSD) with regard to surgical
      techniques and early and midterm results. STUDY DESIGN: Forty-six patients were
      treated for complete (n=28) or partial (n=18) AVSD between 2000 and 2007. There
      were nine boys and 19 girls (mean age 5.5 months; range 1.5 to 11 months) with
      complete AVSD. Of these, 17 patients underwent total repair, while 11 patients
      underwent palliative procedures. Five males and 13 females (mean age 11 years;
      range 1 to 50 years) with partial AVSD were treated with total repair. Down
      syndrome was seen in nine patients (32.1%) and one patient (5.6%) in complete and
      partial AVSD groups, respectively. Twenty-one patients (75%) and 14 patients
      (77.8%) could be followed-up for a mean of 26.3 months (range 1-72) and 21.8
      months (range 2 to 71) in the two groups, respectively. RESULTS: Total repair of
      partial AVSD resulted in no mortality or significant morbidity. Early
      postoperative mortality occurred in three cases (10.7%) after repair of complete
      AVSD, one of which had Down syndrome. Six patients required prolonged mechanical
      ventilation beyond one week. Two patients without Down syndrome underwent
      reoperation due to severe atrioventricular (AV) valve insufficiency in the early
      postoperative period. None of the patients required permanent pacemaker
      implantation. Clinical and echocardiographic monitoring showed moderate left AV
      valve insufficiency in three patients in each group, while the remaining patients
      had no or minimal insufficiency. CONCLUSION: Total repair of complete AVSD should
      be the procedure of choice in early infancy. Left AV valve insufficiency
      continues to be the most important cause of postoperative morbidity in these
      cases.

PMID- 18626210
TI  - Unoperated tetralogy of Fallot in a 68-year-old patient.
AB  - Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease,
      generally treated with total correction within the first two years of life.
      Occasionally, some unoperated cases can reach older ages. A 68-year-old woman
      with diabetes mellitus presented with swelling in legs and abdomen, weakness,
      exertional dyspnea, and orthopnea. On physical examination, she had mild cyanosis
      with clubbing. Her blood pressure was 110/60 mmHg and pulse rate was 79 beat/min.
      She had a systolic ejection murmur and bilateral rales on basal lung areas.
      Massive edema was noted in both lower limbs. Electrocardiography showed atrial
      fibrillation with normal ventricular response. Chest radiography showed an
      increased cardiothoracic ratio and bilateral minimal pleural effusion.
      Echocardiography showed biatrial dilatation (right atrium 62 mm, left atrium 49
      mm) and thickening of left ventricular walls. There was right ventricular
      hypertrophy with decreased systolic function. A very large ventricular septal
      defect and severe pulmonary stenosis were noted. The patient did not accept any
      interventional procedure. To our knowledge, this is the oldest unoperated TOF
      case reported from our country.

PMID- 18626211
TI  - Unruptured and ruptured sinus of Valsalva aneurysms in two cases.
AB  - Sinus of Valsalva aneurysms (SVA) are relatively rare lesions with a variable
      clinical presentation. We presented two patients, one of whom (male, aged 96
      years) had an unruptured asymptomatic right SVA without a left-to-right shunt to
      the right ventricle, and the other (male, aged 33 years) a fistula from the right
      sinus of Valsalva to the right atrium due to nonpenetrating thoracic trauma. The
      diagnosis was made by echocardiography in both cases. The elderly patient was
      followed-up with medical therapy for a year without any complications. The
      younger patient had complaints of progressive exertional dyspnea and fatigue
      following blunt substernal and thoracic trauma. He underwent successful surgical
      repair of the SVA.

PMID- 18626212
TI  - Left anterior descending coronary artery originating from the pulmonary artery: a
      rarity suspected during echocardiography.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital anomaly that is often referred to as Bland-White-Garland
      syndrome. Isolated anomalous origin of the left anterior descending (LAD) or
      circumflex arteries is even rarer. A 38-year-old woman presented with typical
      angina of about two-year history. Physical examination findings were normal other
      than a grade 3/6 systolic murmur. Electrocardiography showed anterolateral ST
      segment depression and T wave inversion, indicating anterior ischemia. Color flow
      transthoracic Doppler echocardiography showed dilated coronary arteries.
      Parasternal short axis views demonstrated an abnormal flow originating from the
      common pulmonary artery. Upon suspicion of a coronary anomaly, coronary
      angiography was performed. Both the left circumflex (Cx) and right coronary
      arteries (RCA) were found dilated, giving extensive collaterals to the LAD
      artery, which drained into the main pulmonary artery. Computed tomographic
      angiography confirmed that the LAD artery originated from the main pulmonary
      artery. Surgical correction was performed and the LAD artery was re-anastomosed
      to the aorta. Control coronary angiography performed one week after surgery
      showed patent LAD artery and diminished collateral supply from the RCA and Cx
      arteries.

PMID- 18626213
TI  - [A rare coronary anomaly detected during primary percutaneous coronary
      angioplasty: totally occluded left main coronary artery originating from the
      right coronary artery].
AB  - Left main coronary artery originating from the right coronary artery (RCA) is a
      rare anomaly. A 52-year-old male patient was submitted to catheterization
      laboratory for primary percutaneous coronary angioplasty with a diagnosis of
      acute anterior myocardial infarction. He had several risk factors including
      smoking, hypertension, and type 2 diabetes mellitus. Selective right coronary
      angiography showed an eccentric 85% stenosis at the mid-segment of the RCA, and
      the left main coronary artery originating from the right aortic sinus. The
      proximal segment of the left main coronary artery was completely occluded with
      thrombus and there was severe stenosis (95%) at the bifurcation of the left
      anterior descending artery with the circumflex artery. A metal stent was
      implanted in the stenotic segment of the left main coronary artery. The patient
      was discharged on the seventh day of stent implantation without any
      complications. Coronary artery bypass grafting was planned for stenotic lesions
      in the RCA and at the bifurcation of the left anterior descending artery with the
      circumflex artery.

PMID- 18626214
TI  - [A case of type IV dual left anterior descending coronary artery anomaly].
AB  - Dual left anterior descending (LAD) artery is a very rare congenital coronary
      artery anomaly. A 51-year-old woman presented with atypical chest pain and
      palpitation. Electrocardiography showed nonspecific ST-segment depression in
      inferior and lateral leads. Coronary angiography showed a rudimentary LAD artery
      terminating in the midportion of the anterior interventricular sulcus, after
      giving the first septal branch. In right coronary angiography, there was another
      LAD artery originating from the proximal right coronary artery and coursing to
      the anterior interventricular sulcus. This anomaly was consistent with type IV
      dual LAD.

PMID- 18626215
TI  - [Echocardiographic evaluation of prosthetic valve endocarditis].
AB  - Although prosthetic valve endocarditis has a relatively low incidence, it is
      associated with a high risk for mortality and morbidity. Periannular
      complications such as abscess formation, pseudoaneurysm, and fistulas are common
      in prosthetic valve endocarditis, indicating a poor prognosis. Echocardiography
      is a very important diagnostic tool in cases of suspected prosthetic valve
      endocarditis and transthoracic and transesophageal echocardiography should be
      performed without delay. If the initial echocardiographic examination is
      inconclusive and the clinical suspicion of infective endocarditis remains high,
      repeat echocardiography is necessary with an interspersion of 7 to 10 days.

PMID- 18626216
TI  - Efficient tirofiban infusion resulting in resolution of intracoronary thrombus.

PMID- 18626217
TI  - A complication of pacemaker implantation: a large pneumothorax compressing the
      entire left lung.

PMID- 18626231
TI  - Changes in indications for upper gastrointestinal tract endoscopy and endoscopic
      findings during the last fifteen years in south-western Greece.
AB  - BACKGROUND: During the past years, major advances in the management of upper
      gastrointestinal diseases have been achieved. The aim of this study was to
      determine if changes in indications for upper gastrointestinal endoscopy and
      endoscopic findings have occurred during the last 15 years in our area. METHODS:
      Indications for upper gastrointestinal tract endoscopy and endoscopy findings of
      patients who underwent upper endoscopy in years 1990, 1995, 2000, and 2005 in our
      department were compared. RESULTS: Over the 15-year period, the number of
      diagnostic endoscopies performed in our department in years 1990, 1995, 2000, and
      2005 increased (953, 1245, 2350, and 2528, respectively). Acute upper
      gastrointestinal bleeding had become less frequent (40%, 42.8%, 19.7%, 14.3%,
      P<0.001), but dyspepsia (24.4%, 33.6%, 54.3%, 51.3%, P=0.002) and reflux (1.8%,
      1.3%, 5.1%, 10.8%, P=0.005) more frequent indications for upper endoscopy. The
      endoscopic findings of duodenal ulcer (39.1%, 22.5%, 20.5%, 9.3%, P<0.001),
      gastric ulcer (15.9%, 8.3%, 5.7%, 4.6%, P=0.036) as well as erosive
      gastroduodenitis (35.6%, 22.2%, 15.3%, 4.7%, P<0.001) decreased, whereas that of
      reflux esophagitis (3.1%, 10.1%, 12%, 16%, P=0.034) increased. Moreover, the
      percentage of patients with negative endoscopy or minimal endoscopic findings
      (eg, nonerosive gastritis) increased (12.8%, 33.7%, 54.1%, 64.4%, P<0.001).
      CONCLUSIONS: In south-western Greece, dyspepsia and reflux as an indication for
      upper endoscopy have been increasing, whereas acute upper gastrointestinal
      bleeding has been decreasing. The finding of peptic ulcers at the upper
      gastrointestinal tract endoscopy has become significantly less frequent, while
      the percentage of patients with negative results of endoscopy seems to have been
      increasing rapidly.

PMID- 18626232
TI  - The role of carotid plaque vulnerability and inflammation in the pathogenesis of
      acute ischemic stroke.
AB  - BACKGROUND: Increasing evidences show that disruption of carotid plaque followed
      by arterio-arterial thromboembolism is an important mechanism in the generation
      of ischemic stroke. Inflammatory mechanisms play a key role in transforming
      structurally vulnerable plaques into functionally unstable ones. The purpose of
      the present study is to evaluate the roles of carotid plaque vulnerability and
      inflammation in the pathogenesis of acute ischemic stroke. METHODS: Fifty-two
      patients with acute ischemic stroke affecting the anterior circulation (stroke
      group) and 44 with asymptomatic carotid stenosis (asymptomatic group) were
      investigated. Duplex ultrasonography was used to evaluate the characteristics of
      carotid plaque and grading the degree of carotid stenosis. Plaque echogenicity
      was assessed as echolucent, predominantly echolucent, predominantly echogenic, or
      echogenic. Plaque surface was classified as smooth, irregular, or ulcerated. All
      subjects had duplex-determined 50% to 99% carotid stenosis. Serum levels of
      matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases (TIMP
      1), soluble CD40 ligand (sCD40L) and high-sensitivity C-reactive protein (hsCRP)
      were measured. RESULTS: Plaques in the stroke group were echolucent or
      predominantly echolucent, whereas those of the asymptomatic group were
      predominantly echogenic or echogenic plaques (P<0.05). Irregular and ulcerated
      plaques were frequently found in stroke patients, while smooth plaques were
      frequently detected in asymptomatic patients (P<0.05). Serum levels of MMP-9,
      sCD40L, hsCRP were higher in stroke than in asymptomatic patients. By contrast,
      serum TIMP-1 levels were significantly higher in the asymptomatic than in the
      stroke group. CONCLUSIONS: The results suggest that inflammation plays a crucial
      role in carotid plaque vulnerability and, together with carotid plaque
      morphology, in the pathogenesis of acute ischemic stroke.

PMID- 18626233
TI  - Dysfunction of splenic macrophages in cirrhotic patients with hypersplenism and
      HBV infection.
AB  - BACKGROUND: Hepatitis B virus (HBV) reinfection is a difficult problem to manage
      after liver transplantation in patients with cirrhosis. This study was designed
      to investigate the activation type of splenic macrophages in cirrhotic patients
      with hypersplenism and HBV infection to assess the immune function of splenic
      macrophages. METHODS: Fourteen cirrhotic patients with hypersplenism and HBV
      infection and 6 controls were enrolled in the study. Serum lipopolysaccharide
      (LPS) was detected with a limulus assay. The differential expression of cytokines
      by splenic tissue and splenic macrophages between the cirrhosis and control
      groups was compared with cytokine arrays. Furthermore, splenic macrophages were
      cultured and stimulated with LPS, after which tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-12 levels in the supernatant were determined. RESULTS: In
      cirrhotic patients, serum LPS levels increased significantly. Interferon-gamma,
      TNF-beta, and transforming growth factor-beta upregulated, whereas IL-4 and IL-13
      levels did not change in splenic tissue. TNF-alpha upregulated significantly,
      whereas IL-4 and IL-5 levels had no significant changes in splenic macrophages.
      The IL-12 levels in culture media of splenic macrophages from cirrhotic patients
      were significantly lower than in controls after LPS stimulation. CONCLUSION:
      Splenic macrophages may be activated via incomplete M1 activation in cirrhotic
      patients with hypersplenism and HBV infection, and the immune function of splenic
      macrophages is impaired.

PMID- 18626234
TI  - Influence of the level of renal insufficiency on endoscopic changes in the upper
      gastrointestinal tract.
AB  - AIM: Lesions of the gastrointestinal tract are frequent finding in uremic
      patients but their actual nature is not completely clear. The aim of this study
      was to detect any correlation between endoscopic lesions of patients with
      different levels of renal insufficiency. METHODS: This prospective study involved
      244 cases, with dyspeptic difficulties including 124 patients in different stages
      of renal insufficiency, and a control group of 120 patients with normal renal
      function. Upper esophagogastroscopy was performed in all patients because of the
      appearance of dyspeptic difficulties. Helicobacter pylori infection was detected
      by the urease test. RESULTS: H. pylori infection (P=0.009), gastric erosions
      (P=0.019), gastric ulcer (P=0.002), and duodenal ulcer (P<0.001) were more common
      in the control group of patients. Significant negative correlations were found
      between the level of renal insufficiency and H. pylori infection (Kendall's tau=
      0.346; P=0.003), stomach erosions (Kendall's tau=-0.272; P=0.019), stomach ulcer
      (Kendall's tau=-0.347; P=0.003), and duodenal ulcer (Kendall's tau=-0.531;
      P<0.001). CONCLUSIONS: In patients with end stage renal disease, endoscopic
      lesions of the gastrointestinal tract are detected less frequently in relation to
      patients without kidney disease.

PMID- 18626235
TI  - Respiratory effects of tobacco smoking among young adults.
AB  - BACKGROUND: Respiratory symptoms associated with smoking habit seem to be age
      dependent. However, there are few reports about the effect of tobacco in young
      populations. The objective of this study was to analyze the effect of smoking on
      respiratory symptoms and lung function in 23- to 25-year-old adults in Brazil.
      This study had a cross-sectional design and included 2063 young people in the
      city of Ribeirao Preto, Sao Paulo State. METHODS: Subjects completed a
      questionnaire used by the European Community Respiratory Health Survey and
      underwent spirometry and bronchial challenge test with methacholine. Multiple
      logistic regression analysis and multiple linear regression analysis were carried
      out to assess the association between smoking and respiratory symptoms, bronchial
      hyperresponsiveness, forced expiratory volume in 1 second (FEV1), and forced
      vital capacity (FVC), adjusted for confounding variables. RESULTS: Prevalence of
      smoking habit was 17.2% with consumption (median) of 10 cigarettes per day
      (interquartile range 3-20). There was a significant association between smoking
      and respiratory symptoms. Smoking was associated to wheezing with odds ratio
      (95%CI) of 6.11 (4.03-9.28) among those smoking>or=10 cigarettes per day and 3.36
      (2.11-5.37) among those smoking<10 cigarettes per day. Associations were found
      for other respiratory symptoms. Smoking was associated with lower FEV1/FVC ratio.
      No association was detected between smoking and FEV1 or bronchial
      hyperresponsiveness. CONCLUSIONS: These findings highlight the early health
      consequences of smoking among young adults. These results prompt the necessity to
      elaborate urgent programs to reduce tobacco habit in young populations.

PMID- 18626236
TI  - Prevalence of folic Acid and vitamin B12 deficiencies in patients with thyroid
      disorders.
AB  - Although macrocytosis might occur with frequency in patients with thyroid
      disorders, there is controversial information on the metabolic relationship
      between thyroid stimulating hormone (TSH), folic acid and B12 in the general
      population. We performed a retrospective analysis to retrieve results of serum
      folic acid, B12, and TSH performed on consecutive outpatients referred by general
      practitioners for routine blood testing over the last 2 years. A positive,
      significant trend towards increased values of folic acid, but not of B12, could
      be observed across the spectrum of TSH values suggestive for hypo- and
      hyperthyroidism. However, the prevalence of subjects with folic acid or B12
      deficiency did not differ significantly among the subgroups of subjects. In
      multivariable linear regression analysis folic acid, but not B12, was associated
      with TSH levels. These results do not support the routine screening for either
      B12 or folic acid deficiency in subjects with subclinical disturbances of thyroid
      function, though we can not rule out that it might still be useful in patients
      with overt thyroid dysfunction.

PMID- 18626237
TI  - Q fever endocarditis: the Mayo Clinic experience.
AB  - OBJECTIVES: To report the Mayo Clinic experience of Q fever endocarditis.
      BACKGROUND: Q fever endocarditis is rare in North America with few case reports
      in the literature. The Centers for Disease Control lists Q fever as a reportable
      illness but does not differentiate endocarditis as a syndrome in its database.
      METHODS: A search of the database for elevated Q fever IgG serology at our
      institution was conducted from December 1980 to December 2005. Patients with
      elevated serologies were retrospectively identified and their medical records
      were reviewed to determine which cases met criteria for a diagnosis of
      endocarditis. RESULTS: Eight patients with elevated serology were identified. One
      case failed to meet criteria and was therefore excluded. All patients presented
      with fever and had previously diagnosed valvular disease. Only 3 patients had
      valvular vegetations on transesophageal echocardiography. All 7 patients were
      treated with antimicrobial therapy, which was not uniform. Six required surgical
      intervention on the affected valves, and 2 required multiple valve surgeries.
      Follow-up ranged from 1 to 17 years. CONCLUSIONS: Q fever endocarditis is a rare
      disease in the United States, where no reliable reporting exists. Q fever
      endocarditis involves underlying abnormal native valves or prosthetic valves.
      Vegetations are small or absent. Relapses are common. Surgeries are common adding
      to morbidity and cost. The chronicity of the syndrome and its high morbidity
      mandate an increased awareness of the condition in patients with culture-negative
      endocarditis or unexplained perivalvular leaks detected by echocardiography.
      Appropriate diagnosis and tailored treatment are likely to reduce the need for
      repeat surgeries.

PMID- 18626238
TI  - Is anaerobic blood culture necessary? If so, who needs it?
AB  - BACKGROUND: The role of anaerobic blood cultures is not validated, although they
      are drawn routinely. METHODS: We performed a retrospective chart review at a
      private hospital in Japan for patients admitted between July 1, 2004 to June 30,
      2005 to determine patient characteristics resulting in anaerobic blood culture.
      RESULTS: During the study period, 17,775 blood culture bottles were sent for the
      analysis, and 2132 bottles (12.0%) were positive for microbial growth. Bacteria
      were grown from 958 anaerobic bottles (44.7%), and 719 (33.7%) of those were
      judged to represent real infections, which accounted for 410 cases of bacteremia.
      Only 47 cases (11.5%) were detected by anaerobic cultures alone. Among those 47,
      obligate anaerobes represented 12 cases. Clinical evaluation could have predicted
      7 of 12 cases of obligate anaerobic bacteremia. In the remaining 5 cases, the
      source of bacteremia was unclear. There were 2.7 cases of anaerobic bacteremia
      per 1000 blood cultures. The mortality attributable to anaerobic bacteremia was
      50%. Among bacteremic cases not caused by obligate anaerobes yet diagnosed solely
      by anaerobic bottles, either the standard 2 sets of blood were not taken or their
      clinical outcomes were favorable. CONCLUSION: Anaerobic blood culture can be
      avoided in most cases. Anaerobic blood culture may be most helpful when (1)
      bacteremia because of obligate anaerobes is clinically suspected, (2) patients
      are severely immunocompromised, and (3) source of bacteremia is not identified by
      clinical evaluation.

PMID- 18626239
TI  - Therapies to increase high-density lipoprotein cholesterol and their effect on
      cardiovascular outcomes and regression of atherosclerosis.
AB  - Epidemiological studies have shown that decreased level of high-density
      lipoprotein (HDL) cholesterol (C) is an independent inverse predictor of coronary
      artery disease (CAD) even in patients with normal levels of low-density
      lipoprotein (LDL)-C. There is an abundance of evidence in favor of statins and
      aggressive LDL-C lowering therapy for both primary and secondary prevention of
      CAD. In contrast, the evidence for reduction of CAD risk with HDL-C raising
      therapy is relatively thin, partly due to the paucity of effective and safe drugs
      for increasing HDL-C level. However, there are emerging new therapies for raising
      HDL-C level and growing evidence in favor of pharmacologic therapies to raise HDL
      C level. We present in this article a review of pharmacologic therapies that are
      currently available to increase HDL-C level, their safety and efficacy in
      relation to cardiovascular endpoints.

PMID- 18626240
TI  - Pulmonary artery aneurism complicated by mural thrombus: a case report.

PMID- 18626241
TI  - Osteogenesis imperfecta and aortic dissection.
AB  - Osteogenesis imperfecta (OI) is a group of autosomal dominant disorders affecting
      Type I collagen synthesis with the predominant clinical manifestations in
      skeleton, skin, eyes, and teeth. Valvular cardiac manifestations and aortic root
      changes have long been reported. However, aortic dissection and repair were not
      described until 1993, with only 3 more proximal aortic dissections and repair
      noted. We report a fifth case and the first distal dissection. Surgeons
      performing vascular operations will in all probability never have encountered
      vascular repair in those with OI. The reports and this case are strong evidence
      that special efforts are required because of the fragility of tissues and
      propensity for bleeding. Reinforcement of any vascular suture line should be
      considered to reduce failure and bleeding.

PMID- 18626242
TI  - Recurrence of HCV infection in a sustained responder after chemotherapy for non
      Hodgkin's lymphoma: successful retreatment.
AB  - It is known that sustained virological response (SVR) in patients with chronic
      hepatitis C is associated with sustained elimination of hepatitis C virus (HCV)
      and that late relapse after SVR in HCV patients is doubtful. A 47-year-old man
      with chronic hepatitis C genotype 3, achieved SVR after combination treatment
      with pegylated interferon and ribavirine for 6 months. Sixteen months later non
      Hodgkin's lymphoma was diagnosed. After successful completion of chemotherapy for
      non-Hodgkin's lymphoma, he presented with HCV infection recurrence of the same
      genotype. Retreatment with the same schedule resulted in normalization of
      aminotransferases and disappearance of HCVRNA from the serum. This case suggests
      that recurrence of HCV infection in a sustained responder may be probable after
      immunosuppressive therapy. Prevention is currently impossible but retreatment may
      be successful.

PMID- 18626243
TI  - Nocardiosis in adult-onset Still's disease and vasculitis syndrome.
AB  - Four cases of nocardiosis in patients with adult-onset Still disease and
      vasculitis syndrome are presented. Three patients developed lung abscesses and 1
      case developed a brain abscess. All were treated with high-dose corticosteroids,
      and 3 were given cyclosporine when they developed nocardiosis. All patients were
      successfully treated with antibiotics; cyclosporine was discontinued in 2 cases.
      These cases indicate that systemic nocardiosis can develop in patients with
      various rheumatologic diseases who are treated with corticosteroid and
      immunosuppressive drugs such as cyclosporine.

PMID- 18626244
TI  - Eosinophilic colitis in a patient with advanced transitional cell carcinoma of
      the bladder: a paraneoplastic syndrome?
AB  - Eosinophilia associated with tumors is extremely rare. The exact underlying
      pathogenetic mechanisms are not well understood; limited data have been reported
      about granulocyte colony-stimulating factor and interleukin-5 in the development
      of eosinophilia. We report a patient with marked eosinophilia, leukocytosis, and
      eosinophilic colitis presenting with bloody stool. The subsequent diagnosis was
      advanced high-grade transitional cell carcinoma of the bladder. Leukocyte count,
      eosinophil count, and colonoscopic findings returned to normal after surgical
      removal of the tumor. To our knowledge, eosinophilic colonic infiltration as a
      manifestation of transitional cell bladder carcinoma has not been previously
      reported.

PMID- 18626245
TI  - Molecular diagnosis and clinical characterization of pseudohypoparathyroidism
      type-Ib in a patient with mild Albright's hereditary osteodystrophy-like
      features, epileptic seizures, and defective renal handling of uric acid.
AB  - We describe a patient who presented with epileptic seizures unresponsive to
      anticonvulsive treatment. Laboratory investigations demonstrated epileptiform
      seizure activity in the brain but also revealed severe hypocalcemia,
      hyperphosphatemia, and elevated serum parathyroid hormone. In addition, the
      patient showed a reduced serum level of 25-[OH]-vitamin D. The diagnosis of
      pseudohypoparathyroidism type-Ib (PHP-Ib) was made based on these clinical
      findings and upon identification of a 3-kb deletion within the STX16 locus, a
      genetic defect frequently associated with autosomal dominant PHP-Ib. This
      mutation was also present in the patient's unaffected mother and her affected
      sister. Despite the molecular diagnosis of PHP-Ib, which is characterized by
      parathyroid hormone resistance in the absence of Albright's hereditary
      osteodystrophy (AHO), the patient had a round face, slightly short stature, and
      short fourth metacarpals, which were consistent with mild AHO. The patient and
      her affected sister, who lacked AHO-like features, showed reduced serum levels of
      uric acid and increased fractional excretion of uric acid, a finding that was
      reported only once previously for PHP-Ib. Unlike the previous report, the
      fractional uric acid excretion and serum uric acid levels returned to normal in
      our patient and her sister after 3 months of treatment period. These findings
      underscore several important points with respect to the pathogenesis and clinical
      presentation of PHP-Ib. Furthermore, the findings in the index case present
      interesting novel aspects, including a previously undescribed coexistence of the
      3-kb STX16 deletion and AHO-like features and a clinical course complicated by
      concomitant 25-[OH]-vitamin D deficiency, which may have resulted, at least
      partly, from long-term use of antiepileptic drugs.

PMID- 18626247
TI  - Reconstruction of the midface and maxilla.
AB  - PURPOSE OF REVIEW: To review the current classification systems and
      reconstructive options available for restoration of maxillectomy defects. RECENT
      FINDINGS: Defects involving the midface can have a great functional and aesthetic
      impact on the patient. Adequate restoration of the complex three-dimensional
      maxillary structure is required to replace form and function of the native
      tissue. An in-depth discussion of appropriate recipient vessel selection and
      reconstructive options are included in this article. The superficial temporal
      vessel system is presented as a reliable anastomosis site for restoration of
      midfacial defects. In addition, the complications of vein grafting, arteriovenous
      fistula loops and alternative recipient vessels sites are addressed to manage the
      challenge of the vessel-depleted neck. The current indications, advantages and
      disadvantages of local, regional and free-flap reconstructive options available
      for maxillectomy defects are highlighted in order to aid the surgeon in
      appropriate flap selection. SUMMARY: A myriad of reconstructive options are
      available to restore maxillectomy defects. The surgeon must consider each defect
      and the needs of the individual patient when choosing the best suited
      reconstructive technique.

PMID- 18626248
TI  - Clinical application of tissue adhesives in soft-tissue surgery of the head and
      neck.
AB  - PURPOSE OF REVIEW: To evaluate the clinical applications of tissue adhesives in
      soft-tissue surgery of the head and neck, and to highlight the practical and
      theoretical differences between the various synthetic and biologic products.
      RECENT FINDINGS: Fibrin glues have been used extensively in head and neck
      procedures. Fibrin glues have been successfully used to reduce wound drainage and
      to improve other short-term postoperative results. More recently, commercial
      systems have become available that allow easy and rapid isolation of autologous
      tissue adhesives from the patient's own blood during or immediately prior to
      surgery. SUMMARY: There is intuitive appeal of autologous over donor-derived
      products. Platelet-rich adhesives possess the added potential of improving wound
      healing beyond fibrin glues alone. Strong evidence for its efficacy in the
      clinical setting is, however, lacking. Future investigations need to evaluate the
      benefits of autologous products in both complex and high-risk surgical wounds,
      incorporating both short-term and long-term outcome metrics of wound healing and
      fibrosis.

PMID- 18626249
TI  - Reconstructive options for skull defects following translabyrinthine surgery for
      vestibular schwannomas.
AB  - PURPOSE OF REVIEW: Advances in microsurgical techniques have dramatically
      decreased the major complications of translabyrinthine vestibular schwannoma
      surgery. Recent trends in the reconstruction of the skull defect following this
      type of surgery have focused on addressing two postoperative morbidities:
      cerebrospinal fluid leak and postauricular deformity. Various reconstructive
      paradigms have shown an improvement in both areas over traditional techniques.
      Options for addressing these problems continue to evolve as surgeons strive to
      improve patient satisfaction. This review highlights such reconstructive options
      and their respective challenges. RECENT FINDINGS: Current techniques include the
      use of various materials such as hydroxyapatite, titanium and vascularized
      cortical bone flap. Hydroxyapatite and titanium mesh alloplastic reconstruction
      are associated with improved outcome but increased surgical cost. Vascularized
      cranioplasty bone flap appears to achieve the same endpoint with no added cost.
      SUMMARY: Cranioplasty following translabyrinthine vestibular schwannoma excision
      has evolved in an effort to reduce postoperative cerebrospinal fluid leaks and
      cosmetic deformities. Long-term results and cost-benefit analysis are needed to
      determine the efficacy and general application of these techniques.

PMID- 18626250
TI  - Bisphosphonate-induced necrosis of the jaws: a reconstructive nightmare.
AB  - PURPOSE OF REVIEW: Bisphosphonates are used for the management of metastatic bone
      disease, prevention and treatment of osteoporosis and Paget's disease of bone. An
      increasing number of reports have associated the use of bisphosphonates with the
      occurrence of osteoradionecrosis of the jaw. The purpose of this review is to
      summarize the recent literature in this area, specifically focusing on its
      management. RECENT FINDINGS: Osteoradionecrosis of the jaw mostly results from
      the use of intravenous bisphosphonates for metastatic bone disease and multiple
      myeloma; cases from oral treatment for osteoporosis and Paget's disease have also
      been reported. It mostly affects the posterior maxilla, followed by the posterior
      mandible. In more than half of the affected patients, there has been preceding
      dental trauma or procedure. Many treatment modalities have been attempted in
      order to limit disease progression. Conservative management with antibiotic
      therapy and mouthwashes seems to be most beneficial. Surgery should be reserved
      for refractory and symptomatic cases. SUMMARY: It is important for the
      reconstructive head and neck surgeon to recognize the clinical presentation of
      bisphosphonate-induced osteoradionecrosis of the jaw and the role of conservative
      management in consistently achieving good results.

PMID- 18626251
TI  - The utility of microvascular anastomotic devices in head and neck reconstruction.
AB  - PURPOSE OF REVIEW: The use of microvascular anastomotic devices remains
      controversial in head and neck reconstructive surgery. Although more acceptable
      in venous anastomosis, their use in arterial anastomosis remains limited. We
      review the literature to evaluate the evidence both for and against their use, in
      both venous and arterial anastomoses. RECENT FINDINGS: The current literature
      supports the use of anastomotic coupling devices in head and neck reconstructive
      surgery. They have been reported as consistently reducing the anastomotic time
      with an associated reduction in cold ischaemic time. There is no evidence
      available to date that shows different thrombotic rates between anastomotic
      devices and hand sewing or between the different anastomotic devices available in
      the market. SUMMARY: The current literature would support the use of these
      devices in both arterial and venous anastomoses. Many microvascular surgeons
      would prefer to maintain their skills with hand sewing, as the use of an
      anastomotic coupling device is not always possible. Therefore, a hand-sewn
      arterial anastomosis and coupled venous anastomosis is a good compromise until
      larger series of results are available.

PMID- 18626252
TI  - Current concepts in midfacial rejuvenation.
AB  - PURPOSE OF REVIEW: Treatment of the aging midface is an underappreciated element
      of overall facial rejuvenation. The anatomy of the midface and the
      pathophysiology of midface aging both remain somewhat controversial. The quest
      for ideal long-lasting midfacial rejuvenation continues. The purpose of this
      paper is to outline the latest progress in the field of midface rejuvenation.
      RECENT FINDINGS: The complexity of midface anatomy has sparked many new
      investigations. Minimally invasive techniques such as threadlifts have shown
      promise but require further study. Volume augmentation with autologous fat and
      fillers is an important aspect of midface rejuvenation. Nonablative therapies
      offer an attractive concept, but the ideal modality still does not exist.
      Enthusiasm for cheek implants seems to be decreasing in favor of soft-tissue
      based treatments. Open surgical treatment via suspension techniques continues to
      be an important option for surgeons when rejuvenating the aging midface. SUMMARY:
      Cadaver dissection and clinical observation have recently been used to further
      define the complex anatomy of the aging midface. New developments in both
      minimally invasive and open surgical procedures continue to both advance and
      redefine the field.

PMID- 18626253
TI  - Recent advances in presurgical molding in cleft lip and palate.
AB  - PURPOSE OF REVIEW: Although many protocols for treating infants with cleft lip
      and palate have been successful, the severely wide deformities often require a
      multidisciplined team approach. Maxillary appliances have been used for 50 years;
      however, nasal molding is a relatively recent development that has shown progress
      but not without stalwart criticism. RECENT FINDINGS: Presurgical nasal alveolar
      molding is an evolving technique in the treatment of cleft lip and palate. Used
      properly, molding can create improved nasal symmetry in unilateral cases and
      columellar lengthening in bilateral cases. Some regression of improvement is
      often seen in the following years due to differential growth patterns within the
      nasal subunits. The nasal septal and columellar deviation seen in unilateral
      cleft lip and palate can also be improved with a novel device. SUMMARY: Although
      traditional repair of the cleft lip and nasal deformity is often adequate,
      severely wide clefts are amenable to a variety of presurgical measures.
      Presurgical nasal alveolar molding in children with cleft lip and palate allows
      repositioning of the maxillary alveolus and surrounding soft tissues in hopes of
      reducing wound tension and improving results. These techniques can be extremely
      challenging but an excellent addition to a cleft lip and palate team's
      armamentarium.

PMID- 18626254
TI  - Update on perioral cosmetic enhancement.
AB  - PURPOSE OF REVIEW: As our understanding of the perioral region advances and
      procedures available for its treatment increase, we are more able to successfully
      treat the aged perioral region with minimal risk. The aged perioral region has
      traditionally been rejuvenated by direct surgical excision, chemical peels, and
      laser resurfacing. Many minimally invasive techniques are now employed for this
      purpose, including chemodenervation, use of soft tissue fillers, and fat
      grafting. RECENT FINDINGS: Over the last couple of decades, rejuvenation
      techniques have evolved to include chemodenervation, soft tissue fillers, fat
      grafting, and dermabrasion. The present article will review the most recent
      literature regarding the use of these techniques for various perioral age-related
      changes, including rhytids, labiomental folds, nasolabial folds, lip-cheek
      grooves, and thinning lips. Often, these modalities are combined to give the most
      natural aesthetic result. SUMMARY: An increase in our armamentarium of techniques
      and general understanding of the complex perioral region allows us to treat the
      area quite effectively with minimal risk. Volume loss, a key component of
      perioral aging, is best addressed with soft tissue fillers and autologous fat. In
      addition, botulinum toxin helps rest some of the key muscles responsible for
      perioral rhytids. Facial resurfacing techniques are still crucial adjuncts in the
      rejuvenation of this area, and they may be the only treatment that adequately
      addresses multiple deeper perioral rhytids.

PMID- 18626255
TI  - Current trends in otoplasty.
AB  - PURPOSE OF REVIEW: We present basic concepts and current trends in otoplasty,
      through a review of the recent literature. RECENT FINDINGS: Over 200 otoplasty
      techniques have been described, yet most technical advances are minor
      modifications of techniques described 40-50 years ago. These techniques can be
      categorized as cartilage-cutting or cartilage-sparing techniques. Many approaches
      described today seem to combine elements of both. Recent retrospective analyses
      of several popular techniques show each to be effective and reliable, with low
      morbidity. Several technical updates and advances have also been described within
      the last few years. SUMMARY: Otoplasty technique is constantly being modified and
      refined, with its basis in historically reliable techniques. The use of a
      graduated approach, combining elements of various techniques, is a common trend
      in otoplasty today.

PMID- 18626256
TI  - Advances in minimally invasive facial rejuvenation.
AB  - PURPOSE OF REVIEW: Current cosmetic surgical practice for facial rejuvenation has
      undergone a significant change due to the introduction of technologies to improve
      the age-associated changes of the face. The most widely adopted methods of
      minimally invasive facial rejuvenation include the use of neuromuscular blocking
      agents and injectable fillers. The topic of minimally invasive procedures might
      include a variety of subjects including nutritional and hormonal modulation,
      light-based and laser-based therapies, minimal incision surgical procedures, as
      well as the use of botulinum toxin and fillers. The focus of this study will be
      on the minimally invasive facial rejuvenation efforts achieved by injection
      techniques. RECENT FINDINGS: Botulinum A neurotoxin has been shown to be
      effective in the reduction of hyperfunctional lines in the upper and lower face.
      Anatomic areas that have been found to benefit include the glabella, the
      forehead, the periorbital area, lips, and the platysma muscle. The more recently
      introduced hyaluronic acid and other injectable fillers are receiving increasing
      usage. These temporary fillers have been found to improve creases and wrinkles,
      augment deep nasolabial folds, augment thin lips, and improve hollowing in the
      periorbital and other depressions and deformities. SUMMARY: There has been a
      significant paradigm shift in the field of rejuvenation surgery. Injectable
      minimally invasive methods have been offered to remedy age-related and other
      acquired deformities of the head and neck region. These methods have provided
      temporary correction of undesirable characteristic that were traditionally
      approached with more invasive surgically oriented modalities.

PMID- 18626257
TI  - Facial aesthetic surgery with emphasis on rhinoplasty in the Hispanic patient.
AB  - PURPOSE OF REVIEW: Increasingly, more Hispanic patients worldwide are seeking
      cosmetic procedures. Of these, many are facial procedures, most commonly
      rhinoplasties. With the increasing demand to perform these procedures, it becomes
      imperative to try to gain knowledge in the area and offer patients the best
      possible surgical option for their needs. RECENT FINDINGS: Hispanic patients,
      also known as mestizo patients are a growing ethnic group worldwide. Today
      emphasis is placed on evaluating the different facial characteristics, defining
      the specific problems encountered and having an armamentarium of surgical options
      to offer. This is especially true when performing rhinoplasty, one of the most
      common facial plastic procedures performed today in the Hispanic or mestizo
      population. SUMMARY: Facial aesthetic surgery, especially rhinoplasties in
      Hispanic patients should be performed after evaluating the patient's specific
      facial characteristics, making an adequate diagnosis of the existing problems and
      offering the patient surgical options that comply with their aesthetic ideal.

PMID- 18626258
TI  - Contemporary Mohs surgery applications.
AB  - PURPOSE OF REVIEW: The incidence of cutaneous malignancies continues to rise and
      it is likely that the majority of skin cancers referred to otolaryngologists will
      have characteristics that necessitate a more complex and aggressive approach.
      Mohs micrographic surgery is a tissue-sparing technique that allows for excision
      of cancers under complete microscopic control and thus boasts high cure rates.
      This paper reviews the Mohs technique and discusses the current indications for
      Mohs surgery in the head and neck. RECENT FINDINGS: For high-risk basal cell and
      squamous cell carcinomas, studies continue to report superior cure rates with
      Mohs surgery compared with non-Mohs modalities such as standard surgical
      excision. Despite several supporting studies, Mohs surgery for melanoma continues
      to be controversial in the literature, as histological identification of melanoma
      with frozen sections remains challenging despite advances. Other means of margin
      control remain popular among non-Mohs surgeons, including frozen section analysis
      and, more recently, photodynamic delineation. SUMMARY: For cutaneous malignancies
      of the head and neck, Mohs surgery offers the distinct advantages of complete
      microscopic margin control coupled with tissue conservation and thus boasts of
      high cure rates. It is important for otolaryngologists to understand the
      technique and current indications for Mohs surgery.

PMID- 18626259
TI  - State of the art in craniomaxillofacial trauma: frontal sinus.
AB  - PURPOSE OF REVIEW: Many of the successes and controversies in endoscopic
      management of craniofacial trauma are exemplified in the management of frontal
      sinus trauma. RECENT FINDINGS: The effort to reduce surgical morbidity and to
      optimize reconstruction of craniomaxillofacial injuries has resulted in the
      development of less invasive surgical approaches and in the use of computer image
      guidance in surgical planning and execution. Minimally invasive management of
      frontal sinus inflammatory disease has gained wide acceptance. The technology and
      techniques applied to surgery of the floor of the frontal sinus is now being
      applied to the management of frontal sinus trauma. A paradigm shift in the
      treatment of frontal sinus trauma may be underway. SUMMARY: An increasing scope
      of less severe injuries is being managed expectantly with endoscopic frontal
      sinus surgery available for salvage. There may be an overall decrease in the most
      severe frontal sinus injuries owing to enforcement of seatbelt and airbag usage.
      And the most severe injuries are often best managed through cranialization with
      anterior skull base reconstruction. Thus, the role for frontal sinus obliteration
      purely to obviate fractures of the frontal sinus outflow tract may be vanishing.

PMID- 18626260
TI  - Measuring outcomes in facial plastic surgery: a decade of progress.
AB  - PURPOSE OF REVIEW: To describe contemporary interpretations of 'outcomes
      research' in facial plastic surgery and to summarize and evaluate some of the
      existing validated outcome measures for use in facial plastic surgery. RECENT
      FINDINGS: Outcome measures can be broadly categorized into two categories -
      patient-reported and clinical efficacy measures (observer-based or objective).
      Over the last decade, there has been influx of validated outcome measures, though
      the rigor of validation varies widely, with formal validation being most common
      among the patient-reported outcome measures. Twenty-two validated patient
      reported measures relevant to facial plastic surgery are available to date.
      Observer-based measures for wound healing and facial wrinkling are presented as
      examples of the evolving rigor of validation for clinical efficacy measures.
      SUMMARY: Validated outcome measures are present for many common facial plastic
      surgery conditions and have become more prevalent over the past decade,
      especially for patient-reported outcomes. Challenges remain in harmonizing
      patient-reported and clinical efficacy measures to produce standardized,
      clinically meaningful outcome measures.

PMID- 18626261
TI  - Bibliography. Current world literature. Head and neck reconstruction.

PMID- 18626262
TI  - Preparation of scientific reports on pharmacokinetic drug interaction studies.

PMID- 18626263
TI  - Short-term testosterone augmentation in male schizophrenics: a randomized, double
      blind, placebo-controlled trial.
AB  - Although there are few studies on the treatment of schizophrenia with
      testosterone, several indirect findings have suggested testosterone as a possible
      treatment modality for schizophrenia. To explore the therapeutic effect of
      testosterone augmentation of antipsychotic medication on symptoms in male
      patients with schizophrenia, the authors performed a placebo-controlled, double
      blind trial on 30 schizophrenic men, using either 5 g of 1% testosterone gel
      (Testogel; Besins Iscovesco, Paris, France) or a placebo added to a fixed dosage
      of antipsychotic medication over a period of 4 weeks with a 2-week washout
      period. In addition, to get additional information about the involvement of these
      reproductive hormones after testosterone augmentation, the authors evaluated
      several hormones such as total testosterone, free testosterone,
      dehydroepiandrosterone sulfate, estradiol, and prolactin. Results indicated a
      significant improvement of negative symptoms in both the last observation carried
      forward and the completer analyses and a nonsignificant trend for the improvement
      of depressive symptoms in completers. There were no significant changes in serum
      hormone levels except total and free testosterone. The findings of this study
      suggest that testosterone augmentation may be a potential therapeutic strategy in
      patients with schizophrenia.

PMID- 18626264
TI  - Fracture risk from psychotropic medications: a population-based analysis.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and
      antipsychotics have each been associated with an increased risk of fracture in
      older individuals. The aim of this study was to better define the magnitude of
      fracture risk with psychotropic medications and to determine whether a dose
      effect relationship exists. METHODS: Population-based administrative databases
      were used to examine psychotropic medication exposure and fractures in persons
      aged 50 years and older in Manitoba between 1996 and 2004. Persons with
      osteoporotic fractures (vertebral, wrist, or hip [n = 15,792]) were compared with
      controls (3 controls for each case matched for age, sex, ethnicity, and
      comorbidity [n = 47,289]). Medications examined included antidepressants (SSRIs
      vs other monoamines), antipsychotics, lithium, and benzodiazepines. RESULTS:
      Selective serotonin reuptake inhibitors were associated with the highest adjusted
      odds of osteoporotic fractures (odds ratio [OR] = 1.45; 95% confidence interval
      [CI], 1.32-1.59). Other monoamine antidepressants (OR = 1.15; 95% CI, 1.07-1.24)
      and benzodiazepines (OR = 1.10; 95% CI, 1.04-1.16) were also associated with
      greater fracture risk, although the relationship was weaker. Lithium was
      associated with lower fracture risk (OR = 0.63; 95% CI, 0.43-0.93), whereas the
      relationship with antipsychotics was not significant in the models that adjusted
      for diagnoses. A dose-effect relationship was seen with SSRIs and
      benzodiazepines. CONCLUSIONS: This study provides novel insight into the
      relationship between fractures and psychotropic medications in the elderly.
      Selective serotonin reuptake inhibitors seem to have a greater risk than other
      psychotropic classes, and higher doses may further increase that risk. Lithium
      seems to be protective against fractures.

PMID- 18626265
TI  - Standard and higher dose of olanzapine in patients with schizophrenia or
      schizoaffective disorder: a randomized, double-blind, fixed-dose study.
AB  - The objective of this study was to assess the dose-response relationship of
      standard and higher doses of olanzapine in a randomized, double-blind, 8-week,
      fixed-dose study comparing olanzapine 10 (n = 199), 20 (n = 200), and 40 mg/d (n
      = 200) for patients with schizophrenia or schizoaffective disorder and suboptimal
      response to current treatment. Patients meeting criteria for antipsychotic
      treatment resistance were excluded. Dose-response relationship was assessed by
      linear regression analysis with log-transformed dose (independent variable) and
      Positive and Negative Syndrome Scale (PANSS) total score (dependent variable).
      There were no significant dose group differences in patients completing the study
      (overall, 67.8%). All dose groups showed statistically significant improvement in
      PANSS total scores from baseline to end point without significant dose-response
      relationship (P = 0.295). Post hoc analysis of response showed significant
      interaction between baseline PANSS and dose (P = 0.023), indicating better
      response at higher doses for patients with higher baseline PANSS. There was a
      significant dose response for mean change in weight (P = 0.003) with significant
      difference between the 10- and 40-mg-dose groups (P = 0.002; 1.9 [10 mg/d], 2.3
      [20 mg/d], and 3.0 kg [40 mg/d]). There was a significant dose response for
      change in prolactin (P < 0.001) with a significant difference between each group
      (-10.5 [10 mg/d], -1.7 [20 mg/d], and 4.9 ng/mL [40 mg/d]; P < or = 0.018). Over
      8 weeks, non-treatment-resistant patients with schizophrenia or schizoaffective
      disorder responded to all 3 doses of olanzapine, without a statistically
      significant dose-response relationship, suggesting that for many patients with
      schizophrenia or schizoaffective disorder, particularly those who are mildly or
      moderately ill, 10 mg/d should be the initial dose of choice.

PMID- 18626266
TI  - Antipsychotic withdrawal-induced relapse predicts future relapses in
      institutionalized adults with severe intellectual disability.
AB  - Severe intellectual and developmental disabilities are frequently associated with
      aggression toward self and others, destruction of property, and disruption.
      Antipsychotic medications are a mainstay of treatment of such behaviors. National
      and state guidelines suggest stopping these medications or decreasing their
      dosages when possible if patients have maintained stability. The current study
      evaluated the likelihood of future antipsychotic drug withdrawal-induced relapses
      in those individuals where such a relapse had occurred previously. Subjects were
      57 institutionalized adults with severe or profound intellectual disability.
      Between 1990 and 2000, each had experienced an initial activation of maladaptive
      aggressive behaviors after an attempt at antipsychotic drug withdrawal and/or
      termination. Quarterly behavioral reports were evaluated to determine whether
      subsequent antipsychotic drug withdrawal attempts were also associated with
      future relapses. Initial relapse was followed by subsequent antipsychotic drug
      withdrawal attempts in 49 of the 57 individuals. Between 1990 and 2005, 28.6% of
      these 49 subjects had experienced 1, 38.7% had 2, 20.4% had 3, and 8.2% had 4
      additional relapses. Two (4.1%) had not relapsed. Eight individuals remained on
      antipsychotic agents without a subsequent withdrawal attempt. By the end of 2005,
      only 4 (7%) of the 57 individuals had become antipsychotic drug free, 22.8% were
      receiving first-generation antipsychotic agents alone, 45.6% were receiving
      second-generation antipsychotic agents alone, and 24.6% were receiving a
      combination of first- and second-generation antipsychotic agents. Thus, if
      relapse occurs after an antipsychotic drug withdrawal attempt, subsequent
      attempts at withdrawal are also very likely to lead to further relapses.

PMID- 18626267
TI  - Intravenous augmentative citalopram versus clomipramine in partial/nonresponder
      depressed patients: a short-term, low dose, randomized, placebo-controlled study.
AB  - The aim of the present study was to evaluate the efficacy of short-term low-dose
      intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d)
      versus placebo in a sample of patients with MDE and partial or no response to
      selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton
      Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%,
      respectively, compared with pretreatment scores) were selected and randomized to
      citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous
      augmentation. The augmentation regimen lasted 5 days during which patients were
      maintained on their previous treatment with oral SSRIs. Analyses of variance with
      repeated measures on HAM-D(21), collected daily in blind-raters design, were
      performed to detect any change of depressive symptoms between the 3 groups. In
      addition, the number of responders and remitters was computed in the 3 groups of
      treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and
      time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total
      scores in favor of citalopram and clomipramine versus placebo, with a superiority
      of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on
      anxiety-somatization symptoms (P = 0.027). The number of responders was
      significantly superior in the active treatment groups versus the placebo group
      ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the
      number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest
      that both clomipramine and citalopram intravenous augmentation at low doses and
      for a short period are well tolerated and superior to placebo in major
      depressives with partial or no response to oral SSRIs with a possible superiority
      of citalopram over clomipramine with regard to anxiety-somatization symptoms. The
      lack of double-blind conditions and the limited sample size may limit the
      confidence in the reported results, and larger randomized controlled trials are
      warranted to confirm the present findings.

PMID- 18626268
TI  - Selective serotonin reuptake inhibiting antidepressants are associated with an
      increased risk of nonvertebral fractures.
AB  - BACKGROUND: Fractures related to osteoporosis and falling constitute a major
      health problem in the elderly population. Exposure to antidepressants is
      associated with an increased risk of falls and fractures, but most previous
      studies incriminate tricyclic antidepressants (TCAs) rather than selective
      serotonin reuptake inhibitors (SSRIs). OBJECTIVE: To examine the association
      between antidepressants, including TCAs, SSRIs, and other antidepressants and the
      risk of nonvertebral fractures in elderly. DESIGN: Prospective population-based
      cohort study. SETTING: The Rotterdam Study, consisting of 7983 individuals aged
      55 years and older. PARTICIPANTS: All persons from the Rotterdam Study. RESULTS:
      One thousand two hundred nineteen persons experienced a nonvertebral fracture, 25
      during TCA use and 18 during SSRI use. After adjustment for age, sex, lower-limb
      disability, and depression, the risk of nonvertebral fracture was 2.35 (95%
      confidence interval, 1.32-4.18) for current users of SSRIs compared with nonusers
      of antidepressants. Multiple adjusting for many possible risk factors did not
      affect the association. To deal with potential confounding by indication, we
      subsequently restricted the analysis to antidepressant users (n = 1217). Compared
      with past users of TCAs or SSRIs, current users of SSRIs had a 2.07-fold (95%
      confidence interval, 1.23-3.50) increased risk of fracture, which further
      increased with prolonged use. In this analysis, depressive state at baseline and
      during follow-up did not play a role, suggesting absence of confounding by
      indication. The use of TCAs was associated with an increased fracture risk that
      decreased with prolonged use. CONCLUSIONS: Not only users of TCAs but also of
      SSRIs have a significantly increased risk of nonvertebral fractures, in SSRI
      users especially after prolonged use. Despite fewer early adverse effects of
      SSRIs, physicians treating elderly depressive patients should be aware of the
      unfavorable long-term consequence of SSRIs on fracture risk.

PMID- 18626269
TI  - Evaluation of endocrine profile and hypothalamic-pituitary-testis axis in
      selective serotonin reuptake inhibitor-induced male sexual dysfunction.
AB  - PURPOSE: To evaluate endocrine profile and hypothalamic-pituitary-testis (HPT)
      axis in male depressed patients with selective serotonin reuptake inhibitor
      (SSRI)-induced sexual dysfunction (SDF). MATERIALS AND METHODS: Eighty-six
      fertile depressed male patients with SSRI-induced SDF, aged 18 to 50 years, were
      enrolled in the study (group 1). Sixty-two age-matched depressed fertile patients
      who currently receive one of the SSRIs but without SDF (group 2), and 68 age
      matched healthy fertile men who had never received a psychiatric diagnosis (group
      3) served as controls. Pretreatment evaluation included history and physical
      examination and International Index of Erectile Function. Two blood samples were
      drawn from each subject at 20-minute intervals for the determination of the
      resting levels of the following hormones: luteinizing hormone (LH), follicle
      stimulating hormone (FSH), testosterone, prolactin, and estradiol. The HPT axis
      was also assessed using the gonadotropin-releasing hormone test. RESULTS: The
      prevalence of hormonal abnormalities in groups 1, 2, and 3 were 83.7% (72), 51.6%
      (32), and 11.8% (7), respectively (P = 0.001 vs group 1 and 0.007 vs group 2).
      Compared with normal controls, the subjects taking SSRIs had significantly lower
      serum levels of LH, FSH, and testosterone. In addition, there were significantly
      decreased LH and FSH responses to gonadotropin-releasing hormone test in groups 1
      and 2 compared with normal controls. Of patients in groups 1 and 2, 68 (79.1%)
      and 27 (43.5%) had elevated serum levels of prolactin (P = 0.0001 vs group 1 and
      0.001 vs group 2). CONCLUSIONS: Most depressed subjects taking SSRIs with and
      without SDF had diminished HPT axis function. This should be replicated in
      further studies.

PMID- 18626270
TI  - Assessment of the prescription of antidepressant drugs in elderly nursing home
      patients: a clinical and laboratory follow-up investigation.
AB  - The aim of the study was to investigate the use of antidepressant drugs among
      elderly people in nursing homes. Elderly residents who where found to have been
      prescribed at least one antidepressant drug according to the specific medication
      dispensing system were identified in 8 nursing homes in the county of
      Ostergotland, Sweden. Data were collected from the medical record forms at the
      nursing home. Blood samples were drawn for the assessment of drug concentration,
      blood chemistry parameters and cytochrome P450 expression. At least one
      antidepressant drug was prescribed to 38% of elderly people in the nursing home
      studied. A total of 71 patients were evaluated, 80% women and 20% men. The median
      age was 84 years (range, 71-100 years). Indications for antidepressant drug
      treatment were found on 96% of medical record forms (depression, 60%); however,
      information relating to when treatment was initiated could not be found on 34% of
      medical record forms and a clear time schedule for how long this drug treatment
      was planned to continue could not be found either. A possible adverse effect of
      antidepressant drug treatment was retrieved in at least 77% of patients.
      Polypharmacotherapy was common; median number of drugs per patient was 11.
      Concentrations of drugs were higher than expected in 73%. Most patients were
      medicated with citalopram (n = 44). A clear interindividual variability of
      concentrations at each dose level was found for citalopram and for the
      metabolites desmethylcitalopram and didesmethylcitalopram. A significant
      correlation was found between the estimation of creatinine clearance and
      concentration-dose ratio of citalopram. Poor metabolizers, who had been
      prescribed an antidepressant drug that are substrate for the cytochrome P450
      isoenzyme examined, have higher concentrations of prescribed antidepressant drug
      than do non-poor metabolizers in relation to dose. An increase in quality
      contribution to follow-up at antidepressant medications is needed. A more
      frequent clinical use of therapeutic drug monitoring and pharmacogenetic tests in
      addition to therapeutic drug monitoring may be one important tool in this
      process.

PMID- 18626271
TI  - Physiological and subjective responses to controlled oral 3,4
      methylenedioxymethamphetamine administration.
AB  - A randomized, within-subject, double-blind, inpatient study of the physiological
      and subjective effects of oral 3,4-methylenedioxymethamphetamine (MDMA) was
      conducted in human volunteers with previous MDMA experience. Placebo, low (1.0
      mg/kg), and high (1.6 mg/kg) doses of oral MDMA were administered in a controlled
      inpatient setting at least 7 days apart to 6 African American (4 male, 2 female)
      and 2 white (both male) volunteers (mean [SE] age, 21.1 [0.8] years; weight, 77.2
      [7.7] kg). 3,4-Methylenedioxymethamphetamine doses were 46 to 150 mg, in the
      range of typical recreational doses. Participants completed all sessions without
      clinically significant adverse events. 3,4-Methylenedioxymethamphetamine produced
      significant dose-dependent increases in heart rate (highest, 132 bpm), systolic
      (highest, 171 mm Hg) and diastolic (highest, 102 mm Hg) blood pressure, and
      subjective responses for energy level, closeness to others, mind racing,
      heightened senses, and high (evaluated by visual analog scales). Peak effects
      occurred 1 to 2 hours after dose, with no secondary peak. There were no
      significant effects on body temperature (measured at tympanic membrane),
      respiratory rate, or blood oxygen saturation (by pulse oximetry). Although most
      physiological and subjective parameters were significantly correlated with MDMA
      plasma concentrations, correlation coefficients were low and clinically
      insignificant, eliminating the ability to predict effects from single plasma
      concentrations. These findings suggest that oral MDMA in typical recreational
      doses produces short-term effects on cardiovascular function and subjective state
      but that temperature effects may result from interaction with environmental and
      subject factors.

PMID- 18626272
TI  - Tolerability and pharmacokinetics of aripiprazole in children and adolescents
      with psychiatric disorders: an open-label, dose-escalation study.
AB  - This multicenter, open-label, sequential-cohort, dose-escalation study explored
      the tolerability and pharmacokinetics (PK) of aripiprazole up to the maximum
      approved adult dose (30 mg/d) in children and adolescents (aged 10-17 years)
      preferentially with primary psychiatric diagnoses of a bipolar or schizophrenia
      spectrum disorder. During a dose-escalation phase, patients received aripiprazole
      for up to 12 days using forced titration to achieve doses of 20, 25, or 30 mg/d.
      In the subsequent fixed-dose phase, patients received the maximum dose for that
      cohort for an additional 14 days. Tolerability in each fixed-dose cohort was
      assessed by measures including evaluation of spontaneously reported adverse
      events (AEs) and vital signs. If 4 of 6 patients tolerated the maximum dose for
      the cohort, the dose was considered tolerated, and enrollment in the next dose
      level began. Of 21 enrolled patients, 17 completed the fixed-dose phase.
      Aripiprazole treatment was generally well tolerated, with criteria for
      tolerability met for all doses tested. All patients experienced at least 1 AE,
      none of which met the regulatory criteria for a serious AE. There were no deaths
      or clinically relevant changes in vital signs or weight. Aripiprazole PK seemed
      to be linear across the tested dose range and was comparable with previous PK
      observations in adults. This study provides information regarding the
      tolerability and PK of aripiprazole up to the maximum adult dose in children and
      adolescents. These data provided support for exploration of a 30-mg/d dose in
      child/adolescent schizophrenia and bipolar disorder.

PMID- 18626273
TI  - Physician Withdrawal Checklist (PWC-20).
AB  - Anxiety disorders are the most common mental illnesses in the United States.
      Despite having a number of medication options readily available, benzodiazepines
      (BZs) and antidepressants have achieved remission rates of only 35% after 8 weeks
      of acute treatment. In the development of new anxiolytics, particularly those
      that affect the gamma-aminobutyric acid system, it is essential to assess the new
      compound's potential to cause discontinuation symptoms after stopping the
      medication as part of both short- and long-term treatment. This report describes
      the development of the 20-item Penn Physician Withdrawal Checklist (PWC), a
      smaller version of the original 35-item PWC, and examines its validity, internal
      consistency, test-retest and interrater reliability, and factor structure. The
      PWC scores, assessed at the peak of withdrawal severity, were selected from 143
      of our patients for an orthogonal factor analysis. Our results suggest that the
      Penn Physician Withdrawal Checklist is a simple and accurate method to assess
      anxiolytic discontinuation symptoms.

PMID- 18626274
TI  - Aripiprazole in a case presenting with tourette syndrome and obsessive-compulsive
      disorder.

PMID- 18626275
TI  - Response to clozapine-induced microscopic colitis: a case report and review of
      the literature.

PMID- 18626276
TI  - Clozapine-induced pericardial effusion.

PMID- 18626277
TI  - Hormonal response to dehydroepiandrosterone administration in schizophrenia:
      findings from a randomized, double-blind, placebo-controlled, crossover study.

PMID- 18626278
TI  - Neuroleptic malignant syndrome and the acute phase response.

PMID- 18626279
TI  - Scientific standards: critical comments on the pharmacoepidemiological study of
      second-generation antipsychotic exposure and metabolic-related disorders in
      patients with schizophrenia.

PMID- 18626281
TI  - Reversible elevation of triglycerides in dual-diagnosis patients taking
      aripiprazole: a case series.

PMID- 18626282
TI  - Impact of study design on the results of continuation studies of antidepressants.

PMID- 18626283
TI  - Mirtazapine-induced akathisia.

PMID- 18626284
TI  - Clinical trials of antidepressants: time to shift to a new model.

PMID- 18626285
TI  - Case report of aripiprazole for persistent developmental stuttering.

PMID- 18626286
TI  - Toxic interaction between valproate and oxcarbazepine: a case detected by the
      free valproate level.

PMID- 18626287
TI  - Disulfiram-induced punding.

PMID- 18626288
TI  - Ultrahigh frequency repetitive transcranial magnetic stimulation in unipolar
      depression.

PMID- 18626289
TI  - SSRI-induced violent suicide: does forensic toxicology hold the answer?

PMID- 18626291
TI  - Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of
      previous wars.
AB  - Differences in the characteristics and mental health needs of veterans of the
      Iraq/Afghanistan war when compared with those of veterans who served in the
      Persian Gulf war and in the Vietnam war may have important implications for
      Veterans Affairs (VA) program and treatment planning. Subjects were drawn from
      administrative data bases of veterans who sought treatment from specialized VA
      programs for treatment of posttraumatic stress disorder (PTSD). Current
      Iraq/Afghanistan veterans were compared with 4 samples of outpatient and
      inpatient Persian Gulf and Vietnam veterans whose admission to treatment was
      either contemporaneous or noncontemporaneous with their admission. A series of
      analyses of covariance was used hierachically to control for program site and
      age. In analyses of contemporaneous veterans uncontrolled for age,
      Iraq/Afghanistan veterans differed most notably from Vietnam veterans by being
      younger, more likely to be female, less likely to be either married or
      separated/divorced, more often working, less likely to have ever been
      incarcerated, and less likely to report exposure to atrocities in the military.
      Regarding clinical status, Iraq/Afghanistan veterans were less often diagnosed
      with substance abuse disorders, manifested more violent behavior, and had lower
      rates of VA disability compensation because of PTSD. Differences are more muted
      in comparisons with Persian Gulf veterans, particularly in those involving
      noncontemporaneous samples, or those that controlled for age differences. Among
      recent war veterans with PTSD, social functioning has largely been left intact.
      There is a window of opportunity, therefore, for developing and focusing on
      treatment interventions that emphasize the preservation of these social assets.

PMID- 18626292
TI  - Narratives by Japanese mothers with chronic mental illness in the Tokyo
      metropolitan area: their feelings toward their children and perceptions of their
      children's feelings.
AB  - Women with mental illness generally have normal fertility rates. Mothers with
      mental illness think that their children are important for their lives but also
      experience difficulties in relating to their children. Therefore, it is important
      to understand the mothers' perception of what experiences influence them or their
      parenting practices in relationships with their children. We conducted narrative
      interviews with 20 Japanese mothers who were being treated for either
      schizophrenia or mood disorders. The data were analyzed using the Modified
      Grounded Theory Approach. For the mothers, their feelings toward their children
      and their perception of their children's feelings toward them or their illness
      influenced the mothers and their parenting practices. Implications for support
      are discussed and directions for future research are presented.

PMID- 18626293
TI  - Autobiography as a tool for self-construction: a study of patients with mental
      disorders.
AB  - The aim of the present study was to explore how the autobiographical process can
      lead to a transformation in the quality of psychiatric patients' self-narrative.
      Fifteen participants, with ages ranging from 25 to 40 years and affected by axis
      I psychiatric disorders (DSM IV), were selected to participate. A 10-question
      interview referring to 10 autobiographical cruxes was used to collect
      autobiographical data; the interview was readministered 2 weeks later. A coding
      system (the N.O.I.S.) was used to analyze each participant's 2 autobiographical
      productions. Results from the second interviews showed significant and positive
      transformations in the quality of patients' autobiographical representation.

PMID- 18626294
TI  - Patient ratings of psychodynamic psychotherapy session activities and their
      relation to outcome.
AB  - This study examines patient ratings of modality-specific technical interventions
      and their relation to therapeutic treatment change. The sample consisted of 55
      individuals engaged in short-term psychodynamic psychotherapy at a university
      based community outpatient treatment center. Results demonstrate that not only
      were patients capable of recognizing specific technical processes occurring
      within their psychotherapy, but also that those ratings were significantly
      related to measures of therapeutic outcome. Furthermore, patient ratings of
      session activities were found to be stable from early session rating to late in
      treatment. Findings support the conclusion that, as rated from the patient
      perspective, some degree of flexibility in and integration of modality-specific
      techniques is beneficial for outcome. Implications for future research and
      clinical practice are discussed.

PMID- 18626295
TI  - Relapse following combined treatment discontinuation in a placebo-controlled
      trial for panic disorder.
AB  - A recent double-blind, placebo-controlled trial (Barlow et al., 2000 JAMA.
      283:2529-2536) examined separate and synergistic effects of psychological and
      pharmacological treatments for panic disorder. One finding warranting further
      investigation involved relatively high relapse rates of participants who received
      cognitive-behavioral therapy (CBT) + imipramine when compared with those
      receiving CBT + placebo. In this article, we investigate why CBT was less
      effective in protecting against relapse for individuals in the active drug
      condition. We hypothesized that participants correctly deduced treatment
      assignments and, for those taking imipramine, this was associated with the belief
      that they were no longer taking active drug after discontinuation, accounting for
      increased relapse rates. Contrary to hypothesis, there were no group differences
      in frequencies of guessing drug or placebo, nor were specific beliefs about
      taking drug or placebo differentially associated with relapse. Other possible
      reasons for differential relapse rates and treatment implications are discussed.

PMID- 18626296
TI  - Interactions between eating disorders and drug abuse.
AB  - To examine the relationship between drug abuse and eating disorders in a
      longitudinal sample. In a prospective study, women diagnosed with either DSM-IV
      anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and
      assessed for research diagnostic criteria drug use disorder (DUD) every 6-12
      months over 8.6 years. Contrary to expectation, DUD did not influence recovery
      from either eating disorder. Multivariate analyses indicated that alcohol use and
      suicide attempts over the course of the study, as well as hospitalization for an
      affective disorder before the study, predicted DUD in anorexia nervosa. For
      bulimia nervosa, multivariate predictors included the severity of alcohol use and
      the severity of bulimic symptoms over the course of the study, and a
      hospitalization before study entry for a nonaffective disorder. Drug abuse in
      women with eating disorders is an area of clinical concern and should be
      monitored routinely.

PMID- 18626297
TI  - Psychometric properties of the Hurricane Coping Self-Efficacy measure following
      Hurricane Katrina.
AB  - The Hurricane Coping Self-Efficacy (HCSE) measure is a validated tool for
      assessing self-efficacy appraisals after hurricanes. Data were collected 6 months
      after Hurricane Katrina from 1542 employed residents of New Orleans, and 181
      participants randomly selected to complete a repeat survey to confirm the
      psychometric properties of the HCSE measure. Overall, coping self-efficacy was
      greater among men, the most educated and those with the highest income.
      Confirmatory factor analyses indicated a relatively good fit of the HCSE items
      into a single construct, with Bentler's comparative fit and McDonald's centrality
      index scores of 0.92 and 0.87, respectively. The repeatability of scores was high
      (Pearson's correlation = 0.70). Additionally, HCSE scores were highly correlated
      with validated scales of perceived stress and posttraumatic stress symptoms, and
      significantly lower scores were observed among participants who sought counseling
      after the storm. The HCSE measure exhibited excellent internal consistency,
      external validity and repeatability after Hurricane Katrina.

PMID- 18626298
TI  - Service user perspectives of a psychoeducation group for individuals with a
      diagnosis of bipolar disorder: a qualitative study.
AB  - Group psychoeducation, incorporating cognitive-behavioral techniques, is
      increasingly used as part of the treatment package for bipolar disorder. The aim
      of this study was to explore service-users' perspectives of a psychoeducation
      group which was run in the context of a community mental health service. Semi
      structured interviews were conducted with 11 participants who had completed a
      psychoeducation group for individuals with a diagnosis of bipolar disorder. The
      verbatim transcripts of those interviews were analyzed using IPA. Three
      superordinate themes emerged from the data, including the treatment of bipolar
      disorder, perception of others, and learning from the group. From the
      perspectives of the service-users, positive working alliances with mental health
      professionals and the need for a treatment strategy that matches the individual's
      own approach to their illness were highlighted as benefits of participation in
      the group.

PMID- 18626299
TI  - A preliminary trial of adherence-coping-education (ACE) therapy for early
      psychosis.
AB  - A pilot randomized controlled trial was conducted to examine the effectiveness of
      adherence-coping-education (ACE) therapy. Twenty-four individuals with early
      psychosis were randomized to receive 14 sessions of either ACE therapy in
      addition to treatment as usual, or supportive therapy in addition to treatment as
      usual. Participants were assessed at baseline, midtreatment, and posttreatment on
      measures of medication attitudes, psychotic and depressive symptoms, and social
      functioning. ACE therapy was well tolerated and was associated with significant
      decrease in symptoms, as well as trend-level improvements in attitudes toward
      treatment. These results lend initial support for the feasibility of ACE Therapy,
      and suggest that it may have promise in facilitating recovery for individuals
      recovering from an initial psychotic episode.

PMID- 18626300
TI  - Measuring money mismanagement among dually diagnosed clients.
AB  - Clients dually diagnosed with psychiatric and substance abuse disorders may be
      adversely affected if they mismanage their Social Security or public support
      benefits. Assistance managing funds, including assignment of a representative
      payee, is available but there are no objective assessments of money
      mismanagement. In this study, a Structured Clinical Interview for Money
      Mismanagement was administered twice at 1-week intervals to 46 clients receiving
      disability payments and was compared with clinician's judgment that the client
      was incapable of managing funds, the frequent basis for payee assignment by the
      Social Security Administration and Veterans Affairs. Clinician's judgment and
      structured interview were concordant on 71% of capability judgments. The
      interview had high test-retest reliability and was correlated with self-reported
      money mismanagement and global assessment of functioning scale scores, but
      clinician judgment was not associated with these measures. Results suggest that
      the interview is sensitive in detecting money mismanagement and raises questions
      concerning the validity of clinicians' judgments.

PMID- 18626301
TI  - Clinical features, outcome, and meningococcal genotype in 258 adults with
      meningococcal meningitis: a prospective cohort study.
AB  - Meningococcal meningitis remains a life-threatening disease. Neisseria
      meningitidis is the leading cause of meningitis and septicemia in young adults
      and is a major cause of endemic bacterial meningitis worldwide. The Meningitis
      Cohort Study was a Dutch nationwide prospective observational cohort study of
      adults with community-acquired bacterial meningitis, confirmed by culture of
      cerebrospinal fluid, from October 1998 to April 2002. Patients underwent a
      neurologic examination at discharge, and outcome was graded with the Glasgow
      Outcome Scale. Serogrouping, multi-locus sequence typing, and susceptibility
      testing of meningococcal isolates were performed. The study identified 258
      episodes of meningococcal meningitis in 258 patients. The prevalence of the
      classical triad of fever, neck stiffness, and change in mental status was low
      (70/258, 27%). When rash was added to the classical triad, 229 of 258 (89%)
      patients had at least 2 of 4 signs. Systolic hypotension was associated with rash
      (22/23 vs. 137/222, p = 0.002) and absence of neck stiffness (6/23 vs. 21/220, p
      = 0.05). Neuroimaging before lumbar puncture was an important cause of delay of
      therapy: antibiotics were not initiated before computed tomography (CT) scan in
      85% of patients who underwent CT scan before lumbar puncture. Unfavorable outcome
      occurred in 30 of 258 (12%) patients, including a mortality rate of 7%.
      Neurologic sequelae occurred in 28 of 238 (12%) patients, particularly hearing
      loss (8%). Factors associated with sepsis and infection with meningococci of
      clonal complex 11 (cc11) are related with unfavorable outcome.

PMID- 18626302
TI  - Histoplasmosis: a study of 158 cases in Venezuela, 2000-2005.
AB  - Histoplasmosis, a granulomatous disease caused by Histoplasma capsulatum, is
      endemic in Venezuela. We conducted the current study to appraise retrospectively
      the demographic data, clinical features, diagnostic methods, and treatment of
      patients with histoplasmosis from January 2000 to December 2005. We reviewed the
      medical records of outpatient cases with a diagnosis of histoplasmosis and
      considered clinical samples processed at our laboratory. We collected
      demographic, epidemiologic, and clinical data from each case as available,
      including results of any mycologic examinations performed. Treatment and outcome
      data were available for some patients. We assessed 158 cases of histoplasmosis:
      103 (65.2%) patients came from the Caracas metropolitan area; 53 were associated
      with acquired immunodeficiency syndrome (AIDS), 14 with tuberculosis, and 8 with
      paracoccidioidomycosis. Six pediatric patients were malnourished. Epidemiologic
      data suggested histoplasmosis in most cases. Patients received treatment with
      itraconazole and/or amphotericin B. Our results may reflect changes in the
      epidemiology occurring in Venezuela, perhaps due to environmental changes and the
      presence of AIDS. Several mycologic exams are necessary to ensure a proper
      diagnosis. More reliable data and statistics on this infection are necessary to
      monitor outbreaks closely and to establish if there is an epidemic pattern.

PMID- 18626303
TI  - Antineutrophil cytoplasmic autoantibody-associated vasculitis in older patients.
AB  - Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is
      increasingly recognized in older patients. The differences in disease
      presentation and outcome between older and younger patients remain controversial.
      We conducted the current study to analyze the characteristics of patients aged
      over 65 years with AAV and to compare the younger and older cohorts. We recruited
      234 consecutive Chinese patients with AAV. We compared clinical and pathologic
      characteristics as well as outcomes between younger and older patients. Among the
      234 patients with AAV, 99 were older than 65 years. Compared with the 135 younger
      patients, the older patients had a significantly higher proportion of positive
      myeloperoxidase-ANCA (94.9% vs. 80.0%, p < 0.01) and a higher proportion of
      microscopic polyangiitis (79.8% vs. 50.4%, chi = 11.8, p < 0.001), but had a
      lower proportion of Wegener granulomatosis (18.2% vs. 37.8%, p < 0.01) and renal
      limited vasculitis (0% vs. 11.1%, p < 0.001).Older patients had more prevalent
      and severe pulmonary involvement than younger patients, including pulmonary
      infiltration, interstitial fibrosis, and mechanical ventilation dependence at
      presentation (47.5% vs. 31.9%, p < 0.05; 37.4% vs. 18.5%, p < 0.01; and 9.1% vs.
      1.5%, p < 0.05, respectively). Older patients were less likely to respond to
      treatment (p < 0.01) and had worse survival than younger patients (p = 0.000).
      During follow-up, older patients had a higher risk of secondary pulmonary
      infection (p < 0.001), and those with pulmonary interstitial fibrosis were more
      likely to develop secondary pulmonary infections (p < 0.05). In conclusion,
      compared with younger patients, older patients with AAV had more severe and more
      prevalent pulmonary lesions, which might contribute to subsequent pulmonary
      infections after the initiation of immunosuppressive therapy. Age and pulmonary
      infection were independent predictors of death.

PMID- 18626304
TI  - Primary Sjogren syndrome in Spain: clinical and immunologic expression in 1010
      patients.
AB  - We conducted the current study to characterize the clinical presentation of
      primary Sjogren syndrome (SS) in a large cohort of Spanish patients and to
      determine whether epidemiologic, clinical, and analytical features modulate
      disease expression. Patients were from the GEMESS Study group, which was formed
      in 2005 and included 12 Spanish reference centers. By March 2007, the database
      included 1010 consecutive patients, recruited since 1994, both incident and
      prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a
      mean age of 53 years at diagnosis and 59 years at inclusion in the registry.
      Multivariate analysis showed that male patients had a lower frequency of
      thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients
      had a low degree of sicca involvement (xerostomia and parotid enlargement) and a
      high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients
      with disease duration of more than 10 years had a higher prevalence of
      xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy
      in comparison with incident cases. The subset of patients with anti-Ro/La
      antibodies had the highest prevalence of most systemic, hematologic, and
      immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid
      scintigraphy, positive salivary gland biopsy, peripheral neuropathy,
      thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with
      a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher
      frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic,
      clinical, and analytical features have a significant impact on the clinical
      presentation of primary SS, influencing the results of the main diagnostic tests,
      the prevalence and diversity of extraglandular involvement, and the frequency of
      the main immunologic markers. Primary SS should be considered as a systemic
      autoimmune disease that can express in many guises beyond sicca involvement.

PMID- 18626305
TI  - Pulmonary veno-occlusive disease: clinical, functional, radiologic, and
      hemodynamic characteristics and outcome of 24 cases confirmed by histology.
AB  - Pulmonary veno-occlusive disease (PVOD) is defined by specific pathologic changes
      of the pulmonary veins. A definite diagnosis of PVOD thus requires a lung biopsy
      or pathologic examination of pulmonary explants or postmortem lung samples.
      However, lung biopsy is hazardous in patients with severe pulmonary hypertension,
      and there is a need for noninvasive diagnostic tools in this patient population.
      Patients with PVOD may be refractory to pulmonary arterial hypertension (PAH)
      specific therapy and may even deteriorate with it. It is important to identify
      such patients as soon as possible, because they should be treated cautiously and
      considered for lung transplantation if eligible. High-resolution computed
      tomography of the chest can suggest PVOD in the setting of pulmonary hypertension
      when it shows nodular ground-glass opacities, septal lines, lymph node
      enlargement, and pleural effusion. Similarly, occult alveolar hemorrhage found on
      bronchoalveolar lavage in patients with pulmonary hypertension is associated with
      PVOD. We conducted the current study to identify additional clinical, functional,
      and hemodynamic characteristics of PVOD. We retrospectively reviewed 48 cases of
      severe pulmonary hypertension: 24 patients with histologic evidence of PVOD and
      24 randomly selected patients with idiopathic, familial, or anorexigen-associated
      PAH and no evidence of PVOD after meticulous lung pathologic evaluation. We
      compared clinical and radiologic findings, pulmonary function, and hemodynamics
      at presentation, as well as outcomes after the initiation of PAH therapy in both
      groups. Compared to PAH, PVOD was characterized by a higher male:female ratio and
      higher tobacco exposure (p < 0.01). Clinical presentation was similar except for
      a lower body mass index (p < 0.02) in patients with PVOD. At baseline, PVOD
      patients had significantly lower partial pressure of arterial oxygen (PaO2),
      diffusing lung capacity of carbon monoxide/alveolar volume (DLCO/VA), and oxygen
      saturation nadir during the 6-minute walk test (all p < 0.01). Hemodynamic
      parameters showed a lower mean systemic arterial pressure (p < 0.01) and right
      atrial pressure (p < 0.05), but no difference in pulmonary capillary wedge
      pressure. Four bone morphogenetic protein receptor II (BMPR2) mutations have been
      previously described in PVOD patients; in the current study we describe 2
      additional cases of BMPR2 mutation in PVOD. Computed tomography of the chest
      revealed nodular and ground-glass opacities, septal lines, and lymph node
      enlargement more frequently in patients with PVOD compared with patients with PAH
      (all p < 0.05). Among the 16 PVOD patients who received PAH-specific therapy, 7
      (43.8%) developed pulmonary edema (mostly with continuous intravenous
      epoprostenol, but also with oral bosentan and oral calcium channel blockers) at a
      median of 9 days after treatment initiation. Acute vasodilator testing with
      nitric oxide and clinical, functional, or hemodynamic characteristics were not
      predictive of the subsequent occurrence of pulmonary edema on treatment. Clinical
      outcomes of PVOD patients were worse than those of PAH patients.

PMID- 18626306
TI  - Bloodstream infections: evolution and trends in the microbiology workload,
      incidence, and etiology, 1985-2006.
AB  - Information available on bloodstream infection (BSI) is usually restricted to
      short periods of time, certain clinical backgrounds, or specific pathogens, or is
      just outdated. We conducted the current prospective study of patients with BSI in
      a 1750-bed teaching hospital to evaluate workload trends and the incidence and
      etiology of BSI in a general hospital during the last 22 years, including the
      acquired immunodeficiency syndrome (AIDS) era. The main outcome measures were
      laboratory workload, trends in incidence per 1000 admissions and per 100,000
      population of different microorganisms, and the impact of the human
      immunodeficiency virus (HIV) epidemic in the period 1985-2006.From 1985 to 2006
      we had 27,419 episodes of significant BSI (22,626 patients). BSI incidence
      evolved from 16.0 episodes to 31.2/1000 admissions showing an annual increase of
      0.83 episodes/1000 admissions (95% confidence interval, 0.61-1.05; p < 0.0001).
      The evolution of the incidence per 1000 admissions and per 100,000 population of
      different groups of microorganisms was as follows: Gram positives 8.2 to
      15.7/1000 admissions and 66.8 to 138.3/100,000 population; Gram negatives 7.8 to
      16.2/1000 admissions and 63.5 to 141.9/100,000 population; anaerobes 0.5 to
      1.3/1000 admissions and 4.1 to 11.7/100,000 population; and fungi 0.2 to 1.5/1000
      admissions and 1.7 to 12.5/100,000 population. All those differences were
      statistically significant. We observed the emergence of multiresistant Gram
      positive and Gram-negative microorganisms. At least 2484 episodes of BSI (9.1%)
      occurred in 1822 patients infected with HIV. The incidence of BSI in HIV-infected
      patients increased from 1985 and reached a peak in 1995 (17.6% of BSI). Since
      1995, the decrease was continuous, and in 2006 only 3.9% of all BSI episodes
      occurred in HIV-positive patients in our institution. We conclude that the BSI
      workload has increased in modern microbiology laboratories. Gram-positive
      pathogens have overtaken other etiologic agents of BSI. Our observation shows the
      remarkable escalation of some resistant pathogens, and the rise and relative fall
      of BSI in patients with HIV.

PMID- 18626307
TI  - Changes in pERK1/2 and pAKT expression in melanoma lesions after imatinib
      treatment.
AB  - Response to treatment with imatinib mesylate has been associated in preclinical
      models with the inhibition of two signaling pathways that promote cellular
      survival - the phosphatidylinositol 3-kinase/AKT pathway and the mitogen
      activated protein kinase/extracellular signal-regulated kinase (ERK) pathway. We
      sought to evaluate the extent of inhibition of these two pathways in metastatic
      melanoma specimens from patients treated with imatinib. Metastatic melanoma tumor
      samples were obtained before and during the second week of imatinib treatment
      from patients enrolled in a phase II study. A tissue microarray was constructed
      using formalin-fixed, paraffin-embedded tissues, and immunohistochemical analysis
      was performed using standard techniques to detect phosphorylated (p) ERK1/2 and
      pAKT expression. Of 21 patients who were treated with imatinib, tumor samples
      adequate for analysis were available both at baseline and during the second week
      of treatment from 10 patients for pERK1/2 expression and from nine patients for
      pAKT expression. No consistent pattern of change in pAKT or pERK expression after
      treatment with imatinib was observed. No apparent correlation between the
      clinical benefit of imatinib treatment and changes in pAKT and pERK1/2 expression
      was observed. A better understanding of the AKT and mitogen-activated protein
      kinase pathways is needed to optimize the clinical benefit of targeted therapy,
      such as imatinib.

PMID- 18626308
TI  - Molecular staging by multimarker reverse transcriptase-polymerase chain reaction
      assay of lymphatic drainage and blood from melanoma patients after lymph node
      dissection.
AB  - Reverse transcriptase-polymerase chain reaction (RT-PCR)-mediated detection of
      melanoma cells may be a prognostic factor for disease outcome. We investigated
      the presence of melanoma cells in lymphatic drainage and blood in melanoma
      patients after lymph node dissection (LND) via the highly sensitive multimarker
      (MM) RT-PCR assay. We collected 24-h lymph fluid (LY) and peripheral blood (BL)
      from 107 stage III melanoma patients after radical LND (59 axillary and 48
      ilioinguinal LND). Tyrosinase, MART1 and uMAGE mRNA levels were determined by RT
      PCR to detect melanoma cells, and the presence of at least one marker signified a
      positive result. All patients underwent follow-up (median for survivors, 21
      months, range: 4-37 months). Forty patients (37.4%) were positive for LY MM RT
      PCR and 28 (26.2%) were positive based on BL MM RT-PCR. No differences for
      disease-free survival (DFS) curves according to BL MM RT-PCR were observed, but
      we found significant differences in the estimated 24-month DFS rate for patients
      with at least one marker and those without any marker in lymph fluid [18.9% (95%
      confidence interval: 1.4-37.5%) and 42.1% (95% confidence interval: 29.7-54.5%),
      median: 9.9 and 15.3 months, respectively] (P=0.04). Detection of multiple
      markers in lymph fluid correlated with shorter DFS. Approximately 37% of lymph
      fluid after radical LND were positive by MM RT-PCR, which correlated
      significantly with early melanoma recurrences and shorter survival. The LY MM RT
      PCR seems to be an effective prognostic tool for stage III melanoma patients. The
      MM RT-PCR analysis of single peripheral blood sample in these patients did not
      have additional prognostic value.

PMID- 18626309
TI  - Sensitivity and specificity of histological criteria in the diagnosis of
      conventional cutaneous melanoma.
AB  - The efficacy of the histological criteria currently used in the diagnosis of
      melanoma is still to be defined. We performed a quantitative analysis of 72
      conventional (non-Spitzoid, nondesmoplastic) melanomas and 73 conventional
      melanocytic naevi, used as controls, for 13 histological diagnostic parameters
      (dimension >6 mm, asymmetry, poor circumscription, irregular and confluent nests,
      single melanocytes predominating, absence of maturation, suprabasal melanocytes,
      asymmetrical melanin, melanin in deep cells, cytological atypia, mitoses,
      necrosis and dermal lymphocytic infiltrate). Differences in the distribution of
      selected parameters between the two groups were investigated by Fisher's exact
      test; for each parameter sensitivity and specificity were calculated. Results
      showed that all parameters, except poor circumscription, seemed to be
      significantly associated with melanoma (P<0.05). Cytological atypia, dermal
      lymphocytic infiltrate, asymmetry, dimension >6 mm and absence of maturation
      showed a high sensitivity (>90%); absence of maturation, mitoses, necrosis,
      asymmetrical melanin, suprabasal melanocytes and melanin in deep cells showed a
      high specificity (>90%); irregular-confluent nests and single melanocytes
      predominating were poorly sensitive and poorly specific. In melanomas < or =2 mm,
      two additional parameters were sensitive (> or =90%): suprabasal melanocytes and
      single melanocytes predominating. We conclude that not all parameters showed to
      have the same diagnostic value. Absence of maturation and, limited to melanomas <
      or =2 mm, suprabasal melanocytes were the most discriminating (sensitive and
      specific) histological features. Cytological atypia, dimension >6 mm, suprabasal
      melanocytes and mitoses were additional reliable diagnostic features, showing a
      relatively high sensitivity and a relatively high specificity. Other useful
      features were dermal lymphocytic infiltrate and asymmetry (sensitive) and
      necrosis, asymmetrical melanin and melanin in deep cells (specific).

PMID- 18626310
TI  - Skin layer-specific Melan-A expression during progression of human cutaneous
      melanoma: implications for diagnostic applications of the marker.
AB  - Melan-A is widely used in the diagnostics of human melanoma. The immunogenicity
      of this glycoprotein makes it a potential target in immunotherapy and several
      authors have suggested its potential as a prognostic factor. Up to now there has
      been no clear direct evidence of changes of Melan-A expression during the
      progression of melanoma. We have performed objective immunohistochemical
      assessment of the expression of Melan-A in benign naevi and melanomas at
      different stages of progression. Our results show a complex pattern of changes in
      the expression of Melan-A in melanomas depending on the location of melanoma
      cells within individual skin layers. The expression of the antigen during tumour
      progression significantly decreases for melanoma cells located in the
      granular/spinous layer (r=-0.94, P=0.02) and increases for the papillary layer
      (r=0.99, P=0.002) and reticular layer (r=0.89, P=0.04). It should also be
      emphasized that from the Clark II level of progression the melanomas can be
      detected with high sensitivity and specificity using a simple cut-off test based
      on the determination of Melan-A expression in tumour cells located within the
      papillary layer.

PMID- 18626311
TI  - Serum matrix metalloproteinase-8 is associated with ulceration and vascular
      invasion of malignant melanoma.
AB  - Serological markers of malignant melanoma have failed to provide prognostic
      significance in patients who are tumour-free after surgery. Immune response
      regulation is important regarding progression and therapeutic interventions of
      malignant melanoma. Matrix metalloproteinase (MMP)-8 is one of the collagenases
      involved in the regulation of tissue remodelling and immune response, being
      incompletely studied in melanoma as yet. We assessed whether serum MMP-8 is of
      prognostic value in malignant melanoma. We studied serum samples of 117 patients,
      of which 63 were stage I, 13 stage II, 12 stage III and 29 stage IV. The mean
      serum MMP-8 levels (47.5 ng/ml) did not significantly correlate with patient or
      tumour characteristics, that is, patient sex, age, tumour Clark's or Breslow's
      classification, sentinel lymph node status or to survival. Importantly, high
      serum MMP-8 levels were significantly related to presence of vascular invasion
      (P=0.001) in primary tumour, tumour ulceration (P=0.003) and tumour bleeding
      (P=0.033). Tendency to increased serum MMP-8 levels in patients with coronary
      heart disease or type II diabetes mellitus was detected. These data imply that
      high serum MMP-8 level is associated with earlier recognized histopathology
      markers of melanoma progression. Results also suggest that elevated serum MMP-8
      might be related to haematogenous spreading of melanoma through vascular
      invasion.

PMID- 18626313
TI  - Spontaneous regression of metastases from malignant melanoma: a case report.
AB  - A case of a 61-year-old male with widespread metastatic melanoma is presented 5
      years after complete spontaneous cure. Spontaneous regression occurred in
      cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature
      reveals seven cases of regression of cerebral metastases; this report is the
      first to document complete spontaneous regression of cerebral metastases from
      malignant melanoma by means of computed tomography scans. Spontaneous regression
      is defined as the partial or complete disappearance of a malignant tumour in the
      absence of all treatment or in the presence of therapy, which is considered
      inadequate to exert a significant influence on neoplastic disease. The incidence
      of spontaneous regression of metastases from malignant melanoma is approximately
      one per 400 patients, and possible mechanisms include immunologic, endocrine,
      inflammatory and tumour nutritional factors. Our patient engaged in alternative
      therapies and was taking a number of different dietary supplements, none of which
      can be medically recommended, but the combination of which possibly strengthened
      the immune system and thereby the host defense against the melanoma metastases.

PMID- 18626312
TI  - Multicenter phase II trial of the histone deacetylase inhibitor pyridylmethyl-N
      {4-[(2-aminophenyl)-carbamoyl]-benzyl}-carbamate in pretreated metastatic
      melanoma.
AB  - Systemic treatment of metastatic melanoma is of low efficacy, and new therapeutic
      strategies are needed. Histone deacetylase inhibitors are supposed to restore the
      expression of tumor suppressor genes and induce tumor cell differentiation,
      growth arrest, and apoptosis. This study was aimed to evaluate the efficacy,
      safety, and pharmacokinetics of the histone deacetylase inhibitor pyridylmethyl-N
      {4-[(2-aminophenyl)-carbamoyl]-benzyl}-carbamate (MS-275) in patients with
      pretreated metastatic melanoma. Patients with unresectable AJCC stage IV melanoma
      refractory to at least one earlier systemic therapy were randomized to receive MS
      275 3 mg biweekly (days 1+15, arm A) or 7 mg weekly (days 1+8+15, arm B), in 4
      week cycles. The primary study endpoint was objective tumor response, secondary
      endpoints were safety and time-to-progression. On the basis of Simon's two-stage
      design, the study initially allowed an entry of 14 patients per arm; if there was
      at least one responder, additional 33 patients were to be enrolled. Among 28
      patients enrolled, no objective response was detected. Four (29%) patients in arm
      A and three (21%) patients in arm B showed disease stabilizations. Median time-to
      progression was comparable in both arms with 55.5 versus 51.5 days, respectively;
      median overall survival was 8.84 months. Toxicity was mild to moderate with
      nausea (39%) and hypophosphatemia (29%) as the most frequently reported events.
      No treatment-related serious adverse events occurred. Single-agent treatment with
      MS-275 was well-tolerated and showed long-term tumor stabilizations, but no
      objective responses in pretreated metastatic melanoma. Further evaluation of MS
      275 in combination schedules is warranted.

PMID- 18626314
TI  - Interrater agreement in rating of pigmented skin lesions for border irregularity.
AB  - The clinical ABCD criteria are still recommended to both physicians and laymen
      when checking moles. The aim of this study was to determine the level of
      interrater reliability and therefore objectivity in rating for one of these
      criteria, namely border irregularity. Five professors, five residents, five
      nurses, and 10 students rated a set of 54 clinical images of pigmented skin
      lesions for border irregularity. After a descriptive presentation, rating was
      again carried out on another set of 54 images. In all groups, the agreement was
      moderate or substantial before the presentation and increased after the
      presentation. An almost perfect agreement was achieved by the professors after
      the presentation. Although both experience and receiving information could
      increase the level of interrater reliability, the disagreement was usually
      sufficient to suggest subjectivity in rating for border irregularity.

PMID- 18626315
TI  - Melanoma presenting as circulating tumor cells associated with failed
      angiogenesis.
AB  - The ability of cancer cells to promote angiogenesis has been associated with a
      transition from a micrometastatic phenotype to a state in which large solid
      metastases can form. We describe a case of metastatic melanoma that presented
      with large numbers of circulating tumor cells and tissue infiltration without
      large solid metastases. Immunohistochemistry and reverse transcriptase-PCR was
      used to study the expression of melanoma tumor markers in circulating tumor
      cells. A tumor cell line was established from the patient and analyzed for
      adhesion molecule expression, expression of vascular endothelial growth factor,
      and the ability to inhibit solid tumor formation by other melanoma cells
      implanted as a xenograft. Examination of the circulating tumor cells confirmed
      they were of melanoma origin. Analysis of the tumor cell line obtained from this
      patient demonstrated intact expression of alpha and beta integrins but poor
      production of vascular endothelial growth factor, and also the ability to inhibit
      solid tumor formation of third-party melanoma tumors, suggesting a strong
      antiangiogenic activity. Our results indicate that lethal metastatic melanoma can
      occur even if tumor angiogenesis is defective, an observation that has
      implications for potential limits of antiangiogenic therapies.

PMID- 18626316
TI  - SPANX-B and SPANX-C (Xq27 region) gene dosage analysis in Sicilian patients with
      melanoma.
AB  - The incidence of melanoma has dramatically increased in many countries (it is 4.5
      cases every 100 000 inhabitants in Sicily) and Xq27 region contains genes
      important in cancer like the SPANX (sperm protein associated with the nucleus in
      the X chromosome) gene family. These genes, made up of two exons separated by an
      intron of about 650 base pair, are expressed in sperm cells and in many tumours,
      including melanoma. These observations suggested that SPANX genes, or some of
      them, may be involved in melanoma development. The aim of this study was to
      investigate the genetic variability of SPANX-B and SPANX-C in a sample of
      Sicilian male population including patients with melanoma of the skin and
      controls. A total of 99 patients were enrolled in this study. They included: 17
      male patients with cutaneous melanoma and 82 normal males. Semiquantitative
      fluorescent multiplex PCR dosage analysis was carried out to identify the variety
      of classes of SPANX-B and SPANX-C genes. Sixteen and 13 genetic classes were
      detected for SPANX-B and SPANX-C genes, respectively. A statistical significant
      difference for a particular class of SPANX-C gene was found comparing patients
      with melanoma and controls (P=0.011). Further investigations should be conducted
      to confirm these observations and to evaluate the possible implication of other
      genes of the region Xq27-28 in melanoma.

PMID- 18626317
TI  - Errors in assessing risk factors for melanoma: lack of reproducibility is the
      minor problem.

PMID- 18626319
TI  - Prevention and management of rhinoplasty complications.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Identify potential hemorrhagic, infectious, traumatic, functional, or
      aesthetic complications arising from rhinoplasty. 2. Gain a better understanding
      of the prevention of these complications. 3. Have a thorough knowledge of the
      principles of postoperative management of these complications, so as to minimize
      their deleterious effects and preserve aesthetic outcomes in rhinoplasty.
      SUMMARY: Meticulous attention to detail in the operating room and in the
      postoperative period is paramount to achieving success in rhinoplasty.
      Nevertheless, both complications and suboptimal results do occur, even for
      experienced surgeons.

PMID- 18626318
TI  - Bisphosphonate-associated osteonecrosis of the jaw: successful treatment at 2
      year follow-up.

PMID- 18626320
TI  - Purtscher's retinopathy as a cause of postoperative blindness.

PMID- 18626321
TI  - Aesthetic surgery in the transplant patient: pushing the envelope?

PMID- 18626322
TI  - Less is more: VRAM inset modification in glossectomy reconstruction.

PMID- 18626323
TI  - Malposition of alar cartilages: a personal modification of the Sheen technique.

PMID- 18626324
TI  - The "butterfly graft" as a treatment for internal nasal valve incompetence.

PMID- 18626325
TI  - Zunyeki technique of nasal tip rotation.

PMID- 18626326
TI  - Repair of question mark ear.

PMID- 18626328
TI  - The composite galeal frontalis pericranial flap designed for anterior skull base
      surgery.

PMID- 18626327
TI  - Aggressive central giant cell lesion of the maxilla: surgical management and the
      use of adjuvant interferon alfa-2a.

PMID- 18626329
TI  - Preoperative planning of the abdominal perforator flap with multidetector row
      computed tomography: 3 years of experience.

PMID- 18626330
TI  - Hidradenitis suppurativa sternalis: surgical treatment of this "no-touch zone." a
      10-year follow-up.

PMID- 18626331
TI  - Pectoralis major perforator flap for filling the lower part of the sternal
      reconstruction defect.

PMID- 18626332
TI  - Enterocutaneous fistula associated with an unrecognized retained vacuum-assisted
      closure sponge.

PMID- 18626333
TI  - Abdominal dermolipectomy: risks and complications in smokers treated from 2004 to
      october of 2006.

PMID- 18626334
TI  - An unusual association of perianal cutaneous vascular lesion, anogenital
      malformations, and tethered spinal cord.

PMID- 18626335
TI  - Gains from the separation of conjoined twins.

PMID- 18626336
TI  - Incidence of mondor disease in breast augmentation: a retrospective study of 2052
      breasts using inframammary incision.

PMID- 18626337
TI  - A new approach to nipple reconstruction: the modified s-flap.

PMID- 18626338
TI  - Striae distensae as a complication of augmentation mammaplasty.

PMID- 18626339
TI  - The smooth spectrum saline implant leakage rate.

PMID- 18626340
TI  - Polyacrylamide hydrogel injection for breast enhancement: should it be banned?

PMID- 18626341
TI  - Multilevel replantation of the palm and digits.

PMID- 18626342
TI  - Hydrosurgical tangential excision of partial-thickness hand burns.

PMID- 18626343
TI  - Posterior interosseous branch palsy following pneumatic tourniquet application
      for hand surgery.

PMID- 18626344
TI  - Skeletal traction treatment of severe finger contracture: a new innovative
      skeletal distraction device.

PMID- 18626345
TI  - The M-shaped thigh lift.

PMID- 18626346
TI  - Secondary free fibular flap for providing rigidity in a radial forearm
      phalloplasty.

PMID- 18626347
TI  - 500 Consecutive patients with free TRAM flap breast reconstruction: a single
      surgeon's experience.
AB  - BACKGROUND: This study reports on the longitudinal experience and outcomes of one
      surgeon performing free transverse rectus abdominis musculocutaneous (TRAM) flaps
      on 500 consecutive patients between 1992 and 2003. METHODS: A retrospective
      review of hospital and outpatient records was performed. Specific risk factors
      for successful reconstruction were reviewed, including American Society of
      Anesthesiologists class, obesity, smoking, medical comorbidities, and irradiation
      and chemotherapy history. Outcomes measured included the length of hospital stay
      and the incidence of complications including both thrombotic and nonthrombotic
      complications. RESULTS: Five hundred sixty-nine free TRAM breast reconstructions
      were performed in a total of 500 patients. Preoperative patient risk factors
      included obesity, smoking, hypertension, diabetes, and cardiac disease, with
      three-fourths of the patients being American Society of Anesthesiologists class
      II or III. Intraoperative or postoperative thrombosis occurred in 35
      reconstructions (6.2 percent). Only one patient had a total flap loss, for a flap
      success rate of 99.7 percent. Significant nonthrombotic complications occurred in
      67 patients (13.4 percent). The most common nonthrombotic complications included
      wound infection (3 percent), fat necrosis (3 percent), and delayed healing (3
      percent). Revision procedures after free TRAM reconstruction were performed in
      14.4 percent of cases. CONCLUSIONS: The free TRAM flap is a highly reliable
      method of autogenous breast reconstruction in a broad spectrum of patients. This
      free flap has a very low thrombotic complication rate, and abdominal donor defect
      problems have been limited. Finally, this method of reconstruction can be
      reliably offered to a wide group of patients, including those considered at high
      risk for a pedicled TRAM flap reconstruction.

PMID- 18626348
TI  - A retrospective analysis of outcomes using three common methods for immediate
      breast reconstruction.
AB  - BACKGROUND: Breast reconstruction outcome studies typically evaluate
      satisfaction, complications, or aesthetic results. Some studies report better
      outcomes with autologous reconstruction, whereas other studies report no
      difference in outcomes across multiple reconstructive methods. METHODS: The
      authors retrospectively studied all patients undergoing immediate breast
      reconstruction over a 5-year period. Questionnaires were sent to all patients to
      assess satisfaction; preoperative bra size, height, and weight; smoking history;
      radiation history; length of stay; narcotic use; and recovery time. All charts
      were reviewed for complications. Four blinded reviewers performed aesthetic
      evaluations of patient results. RESULTS: One hundred eighty-six consecutive
      immediate breast reconstruction patients were surveyed. Charts and photographs
      were reviewed for complication data and aesthetic results. The survey response
      rate was 42 percent, including 48 of 106 expander/implant patients, 13 of 28
      latissimus patients, and 18 of 52 transverse rectus abdominis musculocutaneus
      (TRAM) flap patients. Patient satisfaction was rated as moderate or better for
      93.8 percent of the expander/implant patients, 76.9 percent of the latissimus
      flap patients, and 83.3 percent of the TRAM flap patients. Expander/implant
      patients were significantly more satisfied than latissimus flap patients.
      Complication rates were 21.7 percent for expander/implant patients, 67.9 percent
      for latissimus flap patients, and 26.9 percent for TRAM flap patients.
      Reoperation rates were 11.3 percent for expander/implant patients, 10.7 percent
      for latissimus flap patients, and 5.8 percent for TRAM flap patients. Aesthetic
      scores were significantly higher for TRAM flap patients compared with
      expander/implant and latissimus flap patients. CONCLUSION: High satisfaction
      rates were seen across all three reconstructive groups, with the highest
      satisfaction levels seen in the expander/implant group, despite higher
      reoperation rates and lower aesthetic scores for this group.

PMID- 18626349
TI  - A head-to-head comparison between the muscle-sparing free TRAM and the SIEA
      flaps: is the rate of flap loss worth the gain in abdominal wall function?
AB  - BACKGROUND: Attempts to limit the impact of autogenous breast reconstruction on
      the abdominal wall have led to the use of the muscle-sparing free transverse
      rectus abdominis musculocutaneous (TRAM), the deep inferior epigastric artery
      perforator (DIEP), and the superficial inferior epigastric artery (SIEA) flaps.
      The purpose of this study was to compare the SIEA flap with the muscle-sparing
      free TRAM flap to determine whether gains in abdominal wall function are offset
      by flap-related complications. METHODS: Seventy-two consecutive SIEA flaps were
      compared with 569 consecutive muscle-sparing free TRAM flaps. Outcomes included
      arterial and venous thrombosis, reoperation, abdominal hernia/bulge, seroma,
      hematoma, fat necrosis, delayed wound healing, infection, partial flap loss, and
      total flap loss. Chi-square and Fisher's exact tests were used to determine
      significant differences. RESULTS: In the SIEA group, there was a higher
      percentage of overweight patients (p = 0.0001), bilateral cases (p = 0.0001), and
      smokers (p = 0.0003). Among SIEA flaps, there were two total flap losses (2.9
      percent) and no abdominal morbidity. In the muscle-sparing free TRAM flap group,
      there was one total flap loss (0.18 percent), and a hernia/bulge rate of 1.9
      percent (n = 11). The difference in flap loss rate was significant (p = 0.03).
      There was a higher incidence of vessel thrombosis requiring anastomotic revision
      in the SIEA group, 17.4 percent (n = 12), compared with the free TRAM group, 6.0
      percent (n = 34) (p = 0.0005). CONCLUSIONS: The SIEA flap has a lower rate of
      hernia/bulge and a higher rate of thrombotic complications. Because of the
      emotional and financial cost of these complications, the SIEA flap should be
      undertaken only if strict criteria are met.

PMID- 18626350
TI  - Effects of an autologous flap combined with an implant for breast reconstruction:
      an evaluation of 1000 consecutive reconstructions of previously irradiated
      breasts.
AB  - BACKGROUND: The goal of the authors' study was to determine whether an autologous
      tissue flap, when combined with an implant for breast reconstruction, reduces the
      incidence of implant-related complications in previously irradiated breasts.
      METHODS: The authors reviewed 1000 consecutive cases of implant-based breast
      reconstructions performed in 706 patients at the authors' institution. The median
      age was 49.5 years, and mean follow-up was 22.2 months. Eighty-six patients (8.6
      percent) received preoperative radiation therapy and 43 patients (4.3 percent)
      received postoperative radiation therapy to the reconstructed breast. Breast
      reconstructions were performed using an expander/implant alone in 776 cases, a
      latissimus dorsi flap/implant in 146 cases, and a free transverse rectus
      abdominis musculocutaneous (TRAM) flap/implant in 78 cases. Implant-based
      reconstructions were considered to have failed if an implant was lost because of
      extrusion, infection, or rupture or if implant exchange was required because of a
      severe capsular contracture. RESULTS: In patients who had undergone preoperative
      irradiation, patients with free TRAM flap/implant reconstructions had a
      significantly lower implant loss rate than patients with expander/implant-only
      reconstructions (5.0 percent versus 30.3 percent, p < 0.04). Also, significantly
      fewer reconstructions failed in patients with latissimus dorsi flap/implant
      reconstructions or TRAM flap/implant reconstructions than in patients with
      expander/implant-only reconstructions (15.2 percent or 10.0 percent versus 42.2
      percent, p < 0.03). CONCLUSION: An autologous flap, when combined with an implant
      for breast reconstruction, appears to reduce the incidence of implant-related
      complications in previously irradiated breasts.

PMID- 18626351
TI  - The accuracy of computed tomographic angiography for mapping the perforators of
      the DIEA: a cadaveric study.
AB  - BACKGROUND: The deep inferior epigastric artery (DIEA) perforator flap is
      increasingly used for breast reconstruction, with preoperative imaging sought as
      a means of improving operative outcome. Computed tomographic angiography has been
      recently described as the preferred imaging modality; however, formal evaluation
      of computed tomographic angiography has not been described. A cadaveric study was
      undertaken to evaluate the accuracy of computed tomographic angiography for
      perforator mapping. METHODS: Ten cadaveric hemiabdominal walls from five fresh
      cadavers underwent contrast injection of each DIEA and subsequent computed
      tomographic scanning, with each DIEA and all perforating branches documented.
      Dissection was then performed, with the recording of the course of the DIEA and
      the course of all perforators in each specimen. The concordance of computed
      tomographic angiography with dissection findings was evaluated. RESULTS:
      Cadaveric computed tomographic angiography identified 154 perforators in 10
      hemiabdominal walls. Computed tomographic angiography was highly accurate, with
      eight false-positives and six false-negatives on cadaveric computed tomographic
      angiography, establishing an overall sensitivity of 96 percent and a positive
      predictive value of 95 percent for mapping perforators. For perforators greater
      than 1 mm in diameter, the sensitivity was 100 percent and the positive
      predictive value was 100 percent. CONCLUSIONS: Computed tomographic angiography
      is a highly accurate tool for identifying the perforators of the DIEA before DIEA
      perforator flaps for breast reconstruction. Preoperative identification of these
      vessels can aid planning for the preferred hemiabdomen for dissection, and may
      save operative time, angst, and potentially complications.

PMID- 18626352
TI  - Breast reduction: safe in the morbidly obese?
AB  - BACKGROUND: With an increasing obese population, plastic surgeons are consulted
      by women requesting larger breast reductions, with body mass indices in the obese
      to morbidly obese range (30 to >or=40 kg/m) and breasts considered gigantomastic
      (>2000 g resected from each breast). There have been few descriptions of outcomes
      in the morbidly obese population. Previous literature reports high complication
      rates in obese women and large-volume breast reductions. METHODS: Retrospective
      investigation of 179 reduction mammaplasty patients was performed out to
      determine whether reduction mass, age, body mass index, smoking, method used
      (i.e., vertical pedicle, inferior pedicle/central mound, or free nipple graft),
      and comorbidities influenced complication rates. The patients were categorized by
      size of reduction, age, and body mass index. RESULTS: The overall complication
      rate was 50 percent. There was no statistical difference in the incidence of
      complications attributable to size of reduction, age, or body mass index (p =
      0.37, p = 0.13, and p = 0.38, respectively). Also, smoking status, method used (p
      = 0.65 and p = 0.17, and p = 0.48 and p = 0.1, respectively) and comorbidities
      had no effect on complication rates (reduction size, p = 0.054; age, p = 0.12;
      and body mass index, p = 0.072). There was no significant increase in the rate of
      complications for each body mass index group based on the reduction mass (p =
      0.75, p = 0.89, p = 0.23, and p = 0.07). CONCLUSION: It is as safe to perform
      large-volume breast reductions in the morbidly obese patient with comorbidities
      as in anyone else.

PMID- 18626353
TI  - Options in reconstructing the irradiated breast.
AB  - BACKGROUND: As radiation therapy becomes more prevalent in the treatment of
      breast cancer, more patients requesting breast reconstruction for mastectomy
      defects will have a history of radiation therapy. METHODS: A retrospective chart
      review study was performed of a single surgeon's 5-year experience with
      reconstruction of the irradiated breast. RESULTS: Sixty-six primary patients and
      13 secondary patients were treated over a 5-year period (2001-2005). Of the 66
      primary patients, 25 (38 percent) presented for reconstruction after recurrence
      following prior breast conservation therapy: 12 had prosthetic based
      reconstructions (with or without a latissimus flap) and 13 had autologous
      reconstructions. Twenty-five patients (38 percent) presented after mastectomy
      followed by radiation therapy: six had prosthetic-based constructions and 19 had
      autologous reconstructions. Twelve patients (18 percent) had their
      reconstructions performed before radiation therapy: nine had implant-based
      reconstructions and three had autologous reconstructions. Four patients (6
      percent) presented for corrections of breast conservation therapy deformities.
      One hundred seventy-five total operations were performed for the primary
      patients, with an average of 2.65 operations per patient. Thirteen patients were
      treated secondarily after previous reconstruction at other institutions with a
      variety of reconstruction methods used. Twenty-eight total operations were
      performed for the secondary patients, with an average of 2.2 operations per
      patient. Capsular contracture rates using the prosthetic score are reported.
      CONCLUSIONS: Because of the variability of presentation of the irradiated breast
      cancer patient, there is no one method of reconstruction ideally suited for all
      irradiated patients. In this 5-year review, the authors found that with careful
      patient evaluation and selection, good results can be attained regardless of
      reconstructive method.

PMID- 18626354
TI  - Microarray analysis of the role of regional dura mater in cranial suture fate.
AB  - BACKGROUND: Craniosynostosis, the premature fusion of cranial sutures, results in
      serious neurologic and morphologic abnormalities when left untreated. Surgical
      excision of the fused sutures and remodeling of the skull remains the standard
      therapy. Development of novel, minimally invasive therapies for craniosynostosis
      will undoubtedly be dependent on a more thorough understanding of the molecular
      mechanisms underlying this abnormality. Significant evidence suggests the
      influence of regional dura mater on the behavior of the overlying suture complex.
      The mouse model has been instrumental in investigating this observation because
      of the natural juxtaposition of the posterior frontal suture, which fuses early
      in life, with the other cranial sutures, which remain patent. METHODS: The
      authors used microarray analysis to compare genomic changes in the dura mater
      underlying the posterior frontal and sagittal sutures of mice. Suture-associated
      dura mater was harvested from mice before (postnatal day 5), during (postnatal
      day 10), and after (postnatal day 20) posterior frontal suture fusion (n = 20
      mice for each of the three time points). RESULTS: Microarray results confirmed
      differential regulation of genes involved in paracrine signaling, extracellular
      matrix, and bone remodeling between the dura mater underlying the fusing
      posterior frontal suture and the patent sagittal suture. CONCLUSIONS: These data
      confirm global differences in gene expression between regional dura mater
      underlying fusing and patent sutures. These results provide further insight into
      potential molecular mechanisms that may play a role in cranial suture biology.

PMID- 18626355
TI  - Repairing critical-sized rat calvarial defects with a periosteal cell-seeded
      small intestinal submucosal layer.
AB  - BACKGROUND: Small intestinal submucosa was evaluated as a bioscaffold candidate
      for periosteum-derived osteoblasts, and its suitability as a bone replacement
      material for cranial defects was investigated. METHODS: In the in vitro phase,
      osteoblasts were expanded in osteogenic medium and were then seeded onto small
      intestinal submucosa. To confirm osteoblast phenotype, they were tested for
      alkaline phosphatase, collagen type 1, and calcium expression. In the in vivo
      phase, calvarial critical-sized defects were created in 35 rats. The defects were
      either left untreated for surgical control (group 1), treated with small
      intestinal submucosa alone (group 2), treated with an osteoblast-embedded
      construct (group 3), or treated with an autogenous bone graft (group 4). The
      results were evaluated 12 weeks after surgery with radiopacity measurements and
      with stereologic analysis. RESULTS: Periosteal cells grew successfully in vitro.
      The percentage radiopaque area at the defect was measured to be 42, 74, 76, and
      89 percent for groups 1, 2, 3, and 4, respectively. The pixel intensity of the
      same site was 36.4, 48.1, 47.5, and 54.5 for the same groups, respectively.
      Tissue-engineered constructs did not achieve enough bone formation and
      calcification to be effective as autogenous bone grafts and were not superior to
      the small intestinal submucosa alone. However, both small intestinal submucosa
      and cell-seeded small intestinal submucosa showed significantly more bone
      formation compared with the untreated group. CONCLUSIONS: Although it was
      demonstrated that the small intestinal submucosa itself has osteogenic
      properties, it was not significantly increased by adding periosteum-derived
      osteoblasts to it. The osteogenic properties of small intestinal submucosa are
      promising, and its role as a scaffold should be investigated further.

PMID- 18626356
TI  - Establishing a new orthotopic composite hemiface/calvaria transplantation model
      in rabbits.
AB  - BACKGROUND: Composite tissue allograft transplantation provides a better
      reconstructive option for patients who suffer from extensive craniomaxillofacial
      deformities. However, there is a lack of sufficient experimental data including
      anatomical and immunologic aspects in larger animals. The purpose of this study
      was to develop a new orthotopic composite hemiface/calvaria transplantation model
      in rabbits with which to estimate the feasibility of composite tissue allografts.
      METHODS: A total of 36 rabbits were studied. The anatomical features were
      explored in six rabbits. Group I (n = 6) represented the autograft group. In the
      allograft control group (group II, n = 12) and the treatment group (group III, n
      = 12), orthotopic composite hemiface/calvaria allotransplantations were performed
      from Dutch to Japanese White rabbits. Recipients in the treatment group received
      low-dose cyclosporine A/prednisone combination therapy. Evaluation methods
      included clinical inspection, histologic analysis, immunohistochemistry, and
      radiography. RESULTS: The animals in the autograft group survived indefinitely.
      Four of six nontreated allografts were rejected within 7 to 10 days. In the
      treatment group, five of six recipients showed no signs of rejection up to the
      endpoint of the study. Only one recipient died as a result of anorexia, on day
      18. The histologic outcomes were well correlated with clinical inspection. Bone
      biopsy specimens at posttransplant days 7 and 120 revealed viable bone.
      Radiologic grade at day 120 showed no significant difference between the
      autograft (10.67 +/- 1.03) and treatment groups (9.2 +/- 1.30). CONCLUSIONS: Low
      dose cyclosporine A/prednisone combination therapy does not influence bone
      viability and healing. A new orthotopic hemiface/calvaria allotransplantation
      model was established successfully that allows further studies on reconstruction
      of extensive craniomaxillofacial defects.

PMID- 18626357
TI  - Fluid shear stress magnitude, duration, and total applied load regulate gene
      expression and nitric oxide production in primary calvarial osteoblast cultures.
AB  - BACKGROUND: Successful bone engineering requires an understanding of the effects
      of mechanical stress on osteoblast differentiation. Therefore, we examined the
      effects of varying magnitude and duration of fluid shear stress on factors
      associated with osteoblastic differentiation. METHODS: Using a cone viscometer,
      primary neonatal rat calvarial osteoblasts were exposed to continuous fluid shear
      stress at varying doses: 0.21, 0.43, and 0.85 Pa for varying time periods. Gene
      expression was analyzed using Northern blots and nitric oxide production was
      quantified with the colorimetric Griess reaction. RESULTS: Fluid shear stress
      stimulated comparable transient increases in TGF-beta1 and TGF-beta3 expression
      by 3 hours. TGF-beta1 expression returned to baseline by 12 hours at all shear
      doses. In contrast, TGF-beta3 expression decreased by 22 percent and 47 percent
      at 12 hours in response to 0.43 Pa and 0.85 Pa, respectively. Osteopontin and Msx
      2 expression patterns were consistent with a more differentiated phenotype at all
      shear levels. The maximum level of shear stress increased nitric oxide production
      2.5-fold at 12 hours and 6.0-fold at 24 hours. CONCLUSIONS: These data
      demonstrate differential regulation of TGF-beta1 and TGF-beta3 isoforms with
      fluid shear stress. Furthermore, because osteopontin and Msx-2 changes were
      consistent with progressive differentiation at all levels of shear stress, dosage
      appears to be less important than the presence of an effective physical stimulus.
      Lastly, nitric oxide does not appear to be the primary regulator of early
      transcriptional changes found in this study.

PMID- 18626358
TI  - A pilot study on three-dimensional visualization of perforator flaps by using
      angiography in cadavers.
AB  - BACKGROUND: Perforator flaps have become popular worldwide, in part because of
      their ability to reliably support a large skin territory on a single perforator.
      Although the lead oxide injection technique provides excellent images for
      anatomical study, it is not possible to show the location, course, and direction
      of the source artery. Materialise's Interactive Medical Image Control System
      allows microvascular anatomy to be evaluated in three-dimensions to design
      perforator flaps. METHODS: Two fresh cadavers were injected using the lead oxide
      gelatin injection technique. The cadavers were imaged using a spiral computed
      tomography scanner. The computed tomographic data were transferred to Digital
      Imaging and Communications in Medicine format and imported to a personal
      computer. Three-dimensional reconstructions of various parts of the body were
      then performed using Materialise's Interactive Medical Image Control System
      software. RESULTS: : Three-dimensional visualization of various parts of the body
      was obtained. This technique clearly shows the bone, soft tissue, skin, and
      vascular structures in a layer-by-layer transparent process. The detailed views
      of the microvasculature provide extensive information regarding the course of
      vessels in all layers of tissue. CONCLUSIONS: The intricate vascular details
      captured by this technique clearly demonstrate the three-dimensional anatomy of
      the integument, bone, and soft tissue in a layer-by-layer transparent process. It
      is a powerful, quick, easy method with which to demonstrate cadaver vascular
      anatomy that may be useful in the design of surgical flaps.

PMID- 18626359
TI  - Differential effects of three preparations of human serum on expansion of various
      types of human cells.
AB  - BACKGROUND: To avoid potential risks of animal-derived products such as viral
      transmission and immunologic reactions, usefulness of human-derived products in
      manipulation of cells for cell-based therapies has been investigated but has not
      yet been completely clarified. METHODS: Three types of human sera-serum from
      whole blood, serum from platelet-rich plasma, and serum from platelet-poor plasma
      were prepared from blood samples obtained from the same four volunteers. The
      authors investigated the biochemical profiles of the three serum preparations as
      well as their potential as culture additives using three types of human cells:
      dermal fibroblasts, adipose-derived stem/stromal cells, and umbilical vein
      endothelial cells. RESULTS: Platelet counts differed among serum from whole blood
      (100 percent), platelet-rich plasma (75.1 percent), and platelet-poor plasma
      (12.6 percent), resulting in differential concentrations of platelet-derived
      growth factor and epidermal growth factor, although other biochemical values such
      as total protein and albumin were similar. Serum from whole blood and platelet
      rich plasma highly enhanced proliferation of dermal fibroblasts compared with the
      effects of serum from platelet-poor plasma, but no differences in proliferative
      efficacy were observed in cultures of adipose-derived stem/stromal cells and
      vascular endothelial cells. CONCLUSIONS: Serum from platelet-rich plasma, which
      is less invasive to prepare than serum from whole blood, was superior to serum
      from platelet-poor plasma as a substitute for animal-derived serum in culture
      expansion of dermal fibroblasts. Although autologous or human-derived serum
      preparations may be of great use in cell-based therapies, this usefulness
      strongly depends on the target cell species and the purpose of the cell culture.

PMID- 18626360
TI  - Comparative study of different combinations of microvascular anastomoses in a rat
      model: end-to-end, end-to-side, and flow-through anastomosis.
AB  - BACKGROUND: This study aimed to compare several microvascular anastomotic
      techniques by patency rate using a free flap model in rats. METHODS: A
      microsurgical transfer model of a pectoral skin flap to the cervical region was
      used. In experiment 1, 120 rats were divided into four groups (n = 30 in each
      group) depending on the type of microvascular anastomotic technique. For group 1,
      end-to-end anastomoses were performed for arteries and veins. For group 2, end-to
      side anastomoses were performed for arteries and end-to-end anastomoses were
      performed for veins. For group 3, flow-through anastomoses were performed for
      arteries and end-to-end anastomoses were performed for veins. For group 4, end-to
      end anastomoses were performed for arteries and end-to-side anastomoses were
      performed for veins. Flap survival was assessed on day 3 and the success rates of
      the four groups compared. In experiment 2 (n = 10), postoperative blood flows of
      end-to-end and flow-through arterial anastomoses were measured. RESULTS: : In
      experiment 1, the success rates in groups 1, 2, 3, and 4 were 76.7, 83.3, 100,
      and 83.3 percent, respectively. Differences between group 3 and the other groups
      were statistically significant. In experiment 2, the blood flow of flow-through
      arterial anastomosis (1.8 ml/minute) was much higher than that of end-to-end
      anastomosis (0.18 ml/minute). CONCLUSIONS: : Flow-through arterial anastomosis
      presented a higher blood flow through the anastomotic site, resulting in a higher
      success rate than conventional anastomoses. In veins, end-to-side anastomosis was
      equivalent to end-to-end anastomosis even though the diameter of the donor vein
      was larger than the recipient vein.

PMID- 18626361
TI  - Early surgical intervention for proliferating hemangiomas of the scalp:
      indications and outcomes.
AB  - BACKGROUND: Large hemangiomas of the scalp, though uncommon, present unique
      challenges to the reconstructive surgeon. If not treated early, these lesions can
      result in large areas of alopecia, distortion of the hairline, or deformation of
      the ear. Given these potential complications and the relative pliability and
      redundancy of the infant scalp before 4 months of age, the authors propose early
      surgical excision. METHODS: A retrospective review of the senior author's
      (B.M.Z.) patient records was performed; over a period of 4 years, six infants
      were identified who underwent resection of a large scalp hemangioma. The surgical
      planning and execution of each case and follow-up are detailed. RESULTS: All six
      hemangiomas were excised completely. In five cases, the excisions were performed
      in one stage at or before 4 months of age. In a sixth case, a tissue expander was
      placed before excision and closure in an 18-month-old infant. In three cases,
      significant ear malposition was corrected by removal of the deforming mass. There
      were no complications. CONCLUSIONS: The authors have demonstrated that by taking
      advantage of the greater elasticity of the infant scalp, large hemangiomas of the
      scalp can be aggressively and successfully treated with surgical intervention,
      often in one operation. Beyond the usual indications, early surgical excision of
      scalp hemangiomas may be advantageous and warranted to prevent the development of
      large alopecic areas or the permanent distortion of the hairline and aural
      anatomy.

PMID- 18626362
TI  - Single-stage reconstruction of middle and lower third helical rim defects using
      chondrocutaneous helical rim and lobular advancement flaps and a scaphal
      reduction cartilage graft.

PMID- 18626363
TI  - Submental pedicled perforator flap: V-Y advancement for chin reconstruction.

PMID- 18626364
TI  - Complex perineal and groin wound reconstruction using the extended dissection
      technique of the gracilis flap.
AB  - BACKGROUND: The purpose of this article is to review the applications of the
      extended-dissection technique of the gracilis flap in a high-risk patient
      population with complex wounds requiring more coverage than a standard gracilis
      flap may provide. To our knowledge, this is the first study applying the extended
      dissection technique as described by Hasen et al. to pedicled gracilis flaps.
      METHODS: A chart review conducted from 2003 to 2006 identified 19 consecutive
      patients as having undergone an extended gracilis dissection. Once the pedicle is
      identified on the medial border of the gracilis, dissection continues proximally,
      dividing the rich vascular network of perforators to the adductor muscles. The
      gracilis is then passed beneath the adductor longus and delivered adjacent to the
      sartorius, where dissection proceeds directly down to the profunda femoris.
      RESULTS: All reconstructions were successful. There was one complication
      presenting as a late infection at the donor site. Mean patient age was 66 years
      and nearly all patients had multiple significant comorbidities, including
      diabetes, peripheral vascular disease, and/or radiation therapy. CONCLUSIONS: The
      extended-dissection technique for gracilis harvest has significant benefits for
      use in pedicled flaps, including a greater arc of rotation and no restriction on
      postoperative ambulation or thigh abduction. These factors are particularly
      important in the challenging patient population represented in this study and add
      to the reliability and versatility of the gracilis flap. Anatomical illustrations
      for technical guidance in this procedure are also provided.

PMID- 18626365
TI  - Soft-tissue coverage and outcome of gustilo grade IIIB midshaft tibia fractures:
      a 15-year experience.
AB  - BACKGROUND: The authors describe a 15-year experience with Gustilo grade IIIB
      fractures of the midtibia based on the type and timing of soft-tissue coverage.
      METHODS: A retrospective chart review was performed and patient demographics,
      risk factors, choice and timing of coverage, fracture outcome, and limb survival
      data were collected. RESULTS: Sixty-five fractures were treated. Soft tissue
      coverage was performed either acutely [<1 week (48 percent)] or delayed [>1 week
      (52 percent); with either a soleus muscle flap [group A; n = 25 (38 percent)] or
      a free tissue transfer [group B; n = 40 (62 percent)]. In group A, 17 (68
      percent) were performed acutely (subgroup A1) and eight (32 percent) were delayed
      (subgroup A2). In subgroup A1, eight (47 percent) had uncomplicated healing,
      whereas seven (41 percent) ended in nonunion. In subgroup A2, all eight patients
      went onto nonunion. The overall limb survival rate for group A was 92 percent (n
      = 23). In group B, 14 (35 percent) were performed acutely (subgroup B1) and 26
      (65 percent) were delayed (subgroup B2). In subgroup B1, six (43 percent) had
      uncomplicated healing, and six (43 percent) ended in nonunion. In subgroup B2,
      six (23 percent) healed primarily, and 17 (65 percent) went onto nonunion. The
      overall limb survival rate for group B was 88 percent (n = 45). CONCLUSIONS: Soft
      tissue coverage is not the only determinant for successful outcome. Delayed
      coverage resulted in higher nonunion rates. Despite high nonunion rates, 89
      percent of fractures ultimately healed successfully.

PMID- 18626366
TI  - Recurrence of plantar fibromatosis after plantar fasciectomy: single-center long
      term results.
AB  - BACKGROUND: Plantar fibromatosis is a rare, hyperproliferative, benign lesion of
      the plantar aponeurosis with an unknown cause. Surgical treatment is associated
      with a high recurrence rate and risk of complications. The goal of this study was
      to determine the recurrence rate of plantar fibromatosis after plantar
      fasciectomy at the authors' institute during the past three decades and the
      factors associated with an increased risk for recurrence. METHODS: The study
      group contained 27 patients with plantar fibromatosis, who underwent 40
      operations on 33 feet, including 13 right (39 percent) and 20 left (61 percent)
      feet. RESULTS: The overall recurrence rate was 60 percent. Treating a primary
      lesion with total plantar fasciectomy was associated with the lowest (25 percent)
      and local resection of the lesion was associated with the highest recurrence rate
      (100 percent). There seemed to be a relation between the existence of multiple
      nodules in one foot and a higher recurrence rate. The recurrence of a primary
      lesion treated with fasciectomy combined with postoperative radiotherapy seemed
      to be lower in comparison with the recurrence rate after surgery only.
      CONCLUSIONS: Surgical treatment of plantar fibromatosis is associated with a high
      recurrence rate and indicated only when the lesions are highly symptomatic and
      conservative measures fail. Total plantar fasciectomy is the most successful
      treatment in this study, particularly for primary lesions. The role of
      postoperative radiotherapy should be evaluated further. A prospective multicenter
      study comparing different surgical procedures will be needed to determine the
      type of operation that most effectively eliminates plantar fibromatosis.

PMID- 18626367
TI  - The use of the extended anterolateral thigh flap for reconstruction of massive
      oncologic defects.
AB  - BACKGROUND: Although the anterolateral thigh flap has been used extensively in
      reconstruction, the use of large or extended skin paddles (i.e., >240 cm) is
      thought to be associated with an increased risk of partial flap necrosis. This
      assumption may be attributable to cadaver perfusion studies of isolated
      anterolateral thigh flaps. The authors' clinical experience has shown, however,
      that significantly larger flaps can be reliably harvested based on the standard
      skin perforators. The purpose of this report was therefore to evaluate the
      authors' clinical experience with the extended anterolateral thigh flap for
      reconstruction of oncologic defects. METHODS: All consecutive patients who had
      undergone reconstruction of oncologic defects using an extended anterolateral
      thigh flap (defined as >or=240 cm) were identified. Patient characteristics and
      outcome data were analyzed. RESULTS: Fifteen patients met the inclusion criteria
      (flap size >240 cm) during the study period. The average size of the flaps was
      341 cm (range, 240 to 480 cm). All flaps were perforator flaps and most had one
      perforator. In two patients, anterolateral thigh- and tensor fasciae latae-based
      perforators were used. There was one total flap loss on postoperative day 7
      caused by recipient vessel spasm. One patient had partial necrosis of the distal
      portion of the flap with delayed healing. CONCLUSIONS: The anterolateral thigh
      flap is an excellent choice for massive defects requiring skin and soft-tissue
      coverage. The flap can be extended safely beyond the limit of 240 cm as suggested
      by cadaver perfusion studies. Inclusion of tensor fasciae latae perforators may
      increase the blood supply of the flap proximally; however, in general, a single
      perforator is capable of supplying a large area of the lateral thigh.

PMID- 18626368
TI  - Suture anchor suspension and fascia lata interposition arthroplasty for Basal
      joint arthritis of the thumb.
AB  - BACKGROUND: Although the ideal treatment of thumb basal joint osteoarthritis is
      debated, most surgeons advocate trapeziectomy with ligament reconstruction tendon
      interposition arthroplasty. However, harvesting and weaving autologous tendon
      creates scarring, alters wrist kinetics, may prolong recovery, and is time
      consuming. In this article, the authors propose a new method of arthroplasty
      using suture anchor suspensionplasty and cadaveric fascia lata interposition.
      METHODS: Thirty-eight consecutive patients who underwent 46 thumb carpometacarpal
      joint arthroplasties were analyzed retrospectively. All patients were treated by
      the senior author (J.U.) at one institution over 6 years. Total (n = 17) or
      partial (n = 29) trapeziectomy was performed followed by Mitek suture anchor
      suspension of the first to the second metacarpal and cadaveric fascia lata
      interposition. Preoperative and postoperative evaluations of pain, satisfaction,
      and strength were undertaken in the short term (3 months) and long term (last
      follow-up). Follow-up averaged 4 years. RESULTS: Thirty-one women and seven men
      were treated, all with advanced osteoarthritis (Eaton stage III and IV). In the
      short term, 93 percent of thumbs had excellent pain relief, whereas in the long
      term, pain relief increased to 96 percent. In the short term, 87 percent of cases
      showed high satisfaction, but this increased to 93 percent in the long term.
      Average key pinch and tip pinch improvements were 1.5 kg (76 percent improvement,
      p < 0.001) and 2.0 kg (81 percent improvement, p < 0.001), respectively. Three
      patients had minor complications. CONCLUSIONS: Thumb basal joint arthroplasty
      using suture anchor suspension and fascia lata interposition is a reliable,
      effective, and expeditious technique. It obviates the need for tendon harvest and
      manipulation while treating the underlying pathomechanics of the disorder.

PMID- 18626370
TI  - Outcomes of hand reconstruction in obstetric brachial plexus palsy.
AB  - BACKGROUND: In children with global obstetric brachial plexus palsy,
      prioritization should be first focused on hand reinnervation and then directed to
      shoulder and elbow function. In this study, the surgical strategy for restoration
      of hand function and the methods and outcomes are analyzed. METHODS: Between 1979
      and 2005, 59 patients (61 extremities) underwent reconstruction for hand
      reanimation. The mean follow-up was 7.7 years (range, 2 to 22 years). Of these,
      16 cases underwent primary reconstruction alone, 35 underwent both primary and
      secondary procedures, and 10 late cases underwent palliative surgery. Hand
      function was evaluated with a modified Gilbert- Raimondi hand scale (grades 4 to
      6 were considered useful outcomes). RESULTS: Grade 4 or better functional
      recovery was observed in six of six cases (100 percent) that underwent primary
      reconstruction within the first 3 months of life. These patients did not require
      any secondary procedures. Multiple secondary procedures were necessitated to
      maximize the functional outcome in late cases or in patients with incomplete
      recovery following primary reconstruction. Overall, 46 of 61 cases (75.4 percent)
      achieved grade 4 or greater. The long-term results were better; 23 of 26 cases
      (88 percent) with a follow-up of more than 8 years achieved grade 4 or greater.
      CONCLUSIONS: When primary reconstruction was performed within 3 months,
      functional return to the hand was the greatest and the need for palliative
      surgery was dramatically reduced. For older patients (>or=4 months), secondary
      procedures can significantly enhance hand function. The best results were seen
      when a combination of tendon transfers and free muscles transfers was performed.

PMID- 18626369
TI  - Outcomes of trapeziectomy with a modified abductor pollicis longus suspension
      arthroplasty for the treatment of thumb carpometacarpal joint osteoarthritis.
AB  - PURPOSE: Various arthroplasty procedures have been described for the treatment of
      thumb carpometacarpal joint osteoarthritis. The purpose of this study was to
      determine the outcomes of patients treated with trapeziectomy and a variation of
      abductor pollicis longus suspension arthroplasty. METHODS: Eighteen consecutive
      patients were treated by a single surgeon (K.C.C.) with trapeziectomy and
      abductor pollicis longus suspension arthroplasty (21 thumbs). Prospective
      outcomes data were collected before the operation and at 3, 6, and 12 months
      after surgery. Outcomes were assessed with x-rays, grip/key pinch strength, the
      Jebsen-Taylor test, and the Michigan Hand Outcomes Questionnaire. RESULTS:
      Immediately after surgery, a 32 percent loss in carpometacarpal joint height was
      observed and an additional 11 percent proximal metacarpal migration was observed
      at 1 year. The mean grip strength was 11.1 kg preoperatively and 7.7, 14.3, and
      16.7 kg at 3 months, 6 months, and 1 year postoperatively, respectively. Michigan
      Hand Outcomes Questionnaire results demonstrated improvements in all domains.
      Statistically significant improvements were noted in the domains of overall
      score, from 41 to 67 (p = 0.03); activities of daily living, from 43 to 66 (p =
      0.01); work, from 41 to 65 (p = 0.05); patient satisfaction, from 25 to 68 (p =
      0.01); and pain, which decreased from 73 to 30 (p < 0.01). CONCLUSIONS: Abductor
      pollicis longus suspension arthroplasty is a faster and technically easier
      technique that avoids any additional deficit by using an accessory tendon. This
      procedure gives acceptable patient-rated outcomes, especially in pain relief and
      satisfaction.

PMID- 18626371
TI  - The changing epidemiologic spectrum of single-suture synostoses.
AB  - PURPOSE: Classic literature indicates an infrequency of metopic craniosynostosis
      (3 to 10 percent) compared to other single-suture craniosynostosis. Recent
      observation challenges these conceptions, warranting long-term demographic
      analysis. METHODS: Syndromic craniofacial dysostoses and multiple suture
      involvement were exclusion criteria, leaving only single suture synostoses
      treated between 1975 and 2004. A chart review was performed and patient
      information recorded. Chi square analysis and Fisher's exact were used to
      determine differences in patient characteristics. A Moran's I statistic was used
      to determine differences in spatial means and whether changes in incidence of
      single-suture synostoses over time are a function of regional phenomena. RESULTS:
      Over 800 patients presented to The Children's Hospital of Philadelphia with a
      diagnosis of single-suture synostosis. There was an outpacing of sagittal suture
      involvement over other sutures. Data demonstrate a decrease in unicoronal
      synostosis and an increase in metopic synostosis (p = 0.011). Geostatistical
      analysis reveals increasing separation between populations over the study period:
      9.8 miles in the first 5 years to 20.8 miles in the last 5 years. Metopic
      maternal age increased between 1975-1989 and 1990-2004 (p = 0.002, 0.0002), while
      unicoronal maternal age did not. The proportion of male patients increased
      considerably in the metopic group compared to unicoronals from 1990-2004 (p =
      0.0001), as did the proportion of syndromic metopic patients (p = 0.02).
      Plausible etiologies for these epidemiological shifts are discussed. CONCLUSIONS:
      Metopic synostosis is on the rise. Changing demographic bases and increasing
      proportions of syndromic patients may be clues to the etiology of this
      epidemiologic event.

PMID- 18626372
TI  - Major craniofacial clefts: case series and treatment philosophy.
AB  - BACKGROUND: The treatment of major facial clefts has evolved greatly over the
      past 40 years. Early in the authors' experience, soft tissues were treated by Z
      plasty and local flap rotation, resulting in a patchwork effect and noticeable
      scars. Bony deficits were treated with bone grafts that often failed to restore
      normal facial contour. In 1985, the authors developed a treatment philosophy to
      resolve these issues, and its tenets have formed the foundation of treatment
      since then. METHODS: From January of 1965 to January of 2006, a series of 495
      patients with major craniofacial clefts were treated in the authors' unit. Sixty
      five percent had multiple clefts and 35 percent had a single cleft. In 33 percent
      of patients, the clefts were unilateral and in 67 percent the clefts were
      bilateral. The objectives of the authors' current treatment philosophy are
      restoration of the craniofacial skeleton, reconstruction with skin and soft
      tissue of like color and texture, generous use of tissue expanders, aesthetic
      unit reconstruction, scar location at limits of aesthetic subunits, and symmetric
      repositioning of key facial landmarks. RESULTS: Patients underwent a total of
      1338 operations. Follow-up ranged from 8 months to 35 years. All patients who
      underwent primary reconstruction after 1985 underwent successful reconstruction
      using the aesthetic subunit principle. Fifty-three percent of patients required
      formal craniofacial osteotomy and 24 percent required bone grafting to restore
      the craniofacial skeleton. CONCLUSIONS: The authors' results have improved
      considerably both in primary and in secondary reconstruction by incorporating
      their revised treatment philosophy. The authors have reduced scar visibility and
      facial asymmetry, allowing these patients to live more normal lives.

PMID- 18626373
TI  - A successful algorithm for limiting postoperative fistulae following palatal
      procedures in the patient with orofacial clefting.
AB  - BACKGROUND: Palatal procedures include (1) primary palatoplasty, (2) oronasal
      fistulas repair, and (3) secondary palatoplasty for velopharyngeal insufficiency.
      Any time a palatal procedure is performed, postoperative fistulas remain
      potential consequences. Presented here is a successful algorithm for performing
      palatal procedures and decreasing the rate of postoperative fistulas in a large,
      single-surgeon, consecutive series. METHODS: A retrospective review of all
      consecutive palatal procedures performed between 2002 and 2006 including (1)
      primary palatoplasty, (2) oronasal fistulas repair, and (3) secondary
      palatoplasty for velopharyngeal insufficiency was performed. Cleft Veau type,
      surgical technique, and outcomes are reviewed. The algorithm included (1)
      relaxing incisions, (2) complete intravelar veloplasty, (3) total release of the
      tensor tendon, (4) dissection of the neurovascular bundle with optional osteotomy
      of the foramen, and (5) incorporation of acellular dermal matrix to achieve
      complete nasal lining reconstruction. RESULTS: Two hundred sixty-eight palatal
      procedures were performed: (1) 132 primary Furlow palatoplasties yielding one
      symptomatic post-Furlow palatoplasty fistula (0.76 percent) (acellular dermal
      matrix was used in 39.4 percent of primary palatoplasties); (2) 55 oronasal
      fistula repairs yielding two symptomatic postoperative fistulas (3.6 percent)
      (acellular dermal matrix was used in 90.9 percent of fistula repairs); and (3) 81
      secondary palatoplasties for velopharyngeal insufficiency resulting in no
      postoperative fistulas. Acellular dermal matrix was used in 14.8 percent of
      secondary palatoplasties for velopharyngeal insufficiency. No recommendations for
      speech surgery followed palatoplasty. CONCLUSIONS: Using the proposed algorithm
      in this single-surgeon consecutive series of 268 cases, the authors achieved the
      lowest reported incidence of postoperative fistulas in all forms of palatal
      procedures, including the lowest incidence (0.76 percent) of symptomatic palatal
      fistulas following primary Furlow palatoplasty.

PMID- 18626374
TI  - Follow-up: orthognathic surgery. Is there a future? A national survey.
AB  - BACKGROUND: The authors recently documented a significant decrease in
      orthognathic surgical cases performed by both plastic and oral surgeons in Ohio
      over a recent 5-year period. The main reason noted was related to third-party
      reimbursement. This is a potentially serious issue that may affect the quality of
      health care for patients with dentofacial deformities. Therefore, an expanded
      survey was conducted to determine whether this was indicative of a national
      trend. METHODS: A three-page questionnaire was sent nationally to plastic
      surgeons and oral surgeons who were members of the American Society of
      Maxillofacial Surgery and the American Association of Oral and Maxillofacial
      Surgeons, respectively. Surveys requested information regarding changes in the
      number of orthognathic operations over a 5-year period (1999-2003) and reasons
      for these changes. RESULTS: Of the 3273 surveys sent, 883 were returned,
      representing an overall response rate of 27 percent. Of the 883 returned, 771
      (87.3 percent) were completed by oral surgeons and 112 (12.7 percent) were
      completed by plastic surgeons. The majority surveyed (70.0 percent) noted a
      decrease in the number of orthognathic procedures performed over a 5-year period,
      and 443 (77.3 percent) stated that the decrease was attributable to problems with
      insurance. Professional reimbursement per hour was calculated based on data
      collected from consecutive operations performed at the authors' institution.
      These data demonstrated that reimbursement per hour is significantly lower when
      orthognathic surgery procedures were compared with other standard plastic surgery
      operations. CONCLUSIONS: Orthognathic surgery may rapidly be becoming a cosmetic
      procedure. This has the potential of creating a two-tier system whereby only
      those who can afford it will undergo orthognathic correction.

PMID- 18626375
TI  - Pediatric cranioplasty using particulate calvarial bone graft.
AB  - BACKGROUND: Closure of calvarial defects in children is problematic because the
      supply of autologous bone is limited and alloplastic materials are not advocated.
      The authors previously showed that cranial particulate bone graft applied over
      the coronal gap during primary fronto-orbital advancement reduced the incidence
      of residual osseous defects. The purpose of this study was to determine the
      effectiveness of particulate bone graft for established calvarial defects.
      METHODS: The authors analyzed consecutive children who had undergone cranioplasty
      with inlay particulate bone grafting between 1989 and 2007. Particulate bone was
      harvested from parietal calvaria or from the endocortex of the cranial elements
      using a hand-driven brace and bit. Patient records were reviewed for age at the
      time of cranioplasty, operative indication, size of defect, and length of follow
      up. Outcome variables included persistent osseous defects, need for further
      cranioplasty, and complications. RESULTS: Thirty-eight children had inlay
      particulate bone grafting at an average age of 8.0 years (range, 3 to 20 years).
      The average defect size was 66.5 cm (range, 5 to 250 cm). Indications for inlay
      grafting were revision fronto-orbital advancement, bony gaps following primary
      cranial remodeling, congenital defects, trauma, and tumor. Mean follow-up was 6.1
      years (range, 0.5 to 18 years). Three patients (7.9 percent) had small persistent
      osseous defects, and one (2.6 percent) required another cranioplasty.
      CONCLUSIONS: Inlay autologous cranial particulate bone graft effectively heals
      established cranial defects in children. Particulate bone graft can be harvested
      in infants and young children, does not require neurosurgical assistance, and has
      minimal morbidity.

PMID- 18626376
TI  - Magnetic resonance imaging as an aid in the dynamic assessment of the
      velopharyngeal mechanism in children.

PMID- 18626377
TI  - The comprehensive management of chemosis following cosmetic lower blepharoplasty.
AB  - BACKGROUND: Chemosis can cause persistent discomfort and aggravation in the
      postoperative period following surgery of the eyelids. This article focuses on
      chemosis associated with cosmetic lower blepharoplasty. The cause is
      multifactorial and includes exposure, periorbital edema, and postoperative
      lymphatic dysfunction. METHODS: A chart review of 312 primary bilateral lower
      transcutaneous blepharoplasties was performed. Data were collected to identify
      the incidence of chemosis, define associated etiologic factors, develop a
      chemosis classification system, and outline a successful treatment algorithm.
      RESULTS: The incidence of chemosis was 11.5 percent in this population of lower
      lid blepharoplasty patients. Chemosis presented intraoperatively or up to 1 week
      postoperatively. The median duration was 4 weeks, with a range from 1 to 12
      weeks. Associated etiologic factors included conjunctival exposure, periorbital
      and facial edema, and lymphatic dysfunction. The four general patterns of
      presentation were classified as type 1, acute mild chemosis with complete lid
      closure; type 2, acute severe chemosis that prohibits complete lid closure
      (chemosis-induced lagophthalmos); type 3, subchronic chemosis that persists
      longer than 3 weeks; and type 4, chemosis associated with lower lid malposition.
      Successful treatment existed along a continuum from liberal lubrication to
      ophthalmic steroid preparations and ocular decongestants to eye-patching to minor
      surgical procedures such as drainage conjunctivotomy and temporary tarsorrhaphy.
      In all cases, chemosis ultimately resolved. CONCLUSIONS: Chemosis is a common
      complication of lower blepharoplasty. Pharmacologic, mechanical, and surgical
      therapies may be used alone or in combination for the successful management of
      chemosis. Prevention by minimization of triggering factors intraoperatively and
      immediately postoperatively is important.

PMID- 18626378
TI  - Optimizing blepharoplasty outcomes in patients with previous laser vision
      correction.
AB  - BACKGROUND: Dry eye syndrome, often referred to as dysfunctional tear syndrome,
      can occur following laser vision correction surgery and routine blepharoplasty.
      Identifying patients prone to developing or worsening of dysfunctional tear
      syndrome following blepharoplasty can help optimize surgical outcomes. METHODS:
      The authors highlight the salient features of the dysfunctional tear syndrome
      including key steps in identifying at-risk patients. The authors discuss changes
      in the cornea that occur with keratorefractive surgery and their significance in
      patients seeking blepharoplasty. The authors suggest guidelines for
      blepharoplasty in these patients and discuss the timing of surgery. RESULTS:
      After blepharoplasty, lagophthalmos of the upper lid is a common temporary
      finding. This change in eyelid function may unmask underlying deficiencies in the
      tear film or corneal sensation. Coexisting lower lid malposition can displace the
      existing tear meniscus and increase exposure of the cornea. Whether in
      combination or alone, these findings can create a dry eye problem. Dysfunctional
      tear syndrome should be considered in all patients with a history of laser vision
      correction during the preoperative evaluation for blepharoplasty. Surgeons should
      rely on preoperative history and physical examination, including assessment of
      preoperative eyelid anatomy and the status of the ocular surface. Patients with
      prior laser vision correction should wait at least 6 months before undergoing
      blepharoplasty because of the effects on corneal sensation, tear production, and
      tear film alteration. CONCLUSIONS: Identification and appropriate treatment of
      dysfunctional tear syndrome together with intraoperative modifications will
      optimize postoperative outcomes and avoid a potentially disabling condition after
      blepharoplasty in patients with previous laser vision correction surgery.

PMID- 18626379
TI  - Brachioplasty and concomitant procedures after massive weight loss: a statistical
      analysis from a prospective registry.
AB  - BACKGROUND: A growing number of massive weight loss patients are undergoing
      brachioplasty. The authors analyzed data from a prospective registry of massive
      weight loss patients who underwent brachioplasty alone or with concomitant
      operations to identify statistically significant complications. METHODS: One
      hundred one massive weight loss patients underwent brachioplasty. Outcome
      measures included operative time; time since gastric bypass; need for revision;
      arm liposuction; and complications such as seroma, dehiscence, hematoma,
      infection, and nerve injury. Univariate analyses were performed to assess outcome
      measures. RESULTS: One hundred one patients (97 women and four men; mean age,
      45.9 +/- 10.1 years; mean body mass index, 29 +/- 3.9) with a mean time since
      gastric bypass of 28.5 months (range, 7 to 252 months) underwent brachioplasty.
      Ninety-seven patients (96 percent) had concomitant body contouring procedures;
      23.8 percent had concomitant arm liposuction; and 36 patients had complications
      related to their arms, mostly in the form of a seroma, whereas dehiscence,
      infection, and hematoma were more prevalent with the concomitant procedures.
      Patients with a greater change in body mass index had a higher chance of wound
      infection (odds ratio, 1.1; p = 0.028). Longer operative time was associated with
      increased rates of surgical complications (p = 0.003; odds ratio, 3.8) at the
      operative site. There was a trend toward increased complications when arm
      liposuction was combined with brachioplasty (odds ratio, 2.5; p = 0.05).
      CONCLUSIONS: Brachioplasty is a safe and effective method of treating upper arm
      deformity in the massive weight loss patient. Although patients with greater
      weight loss are likely to present for longer contouring procedures and are at
      highest risk for wound-healing complications, these complications occur most
      frequently in areas other than the arms.

PMID- 18626380
TI  - Nutritional deficiency of post-bariatric surgery body contouring patients: what
      every plastic surgeon should know.
AB  - BACKGROUND: Bariatric surgery, particularly the Roux-en-Y gastric bypass, is
      currently the most effective method of sustainable weight loss for the morbidly
      obese patient population. Unfortunately, the nutritional adequacy of the
      postoperative diet has frequently been overlooked, and in the months to years
      that follow, many nutritional deficiencies have become apparent. Furthermore,
      once weight loss has reached a plateau, many patients become candidates for body
      contouring surgery and other aesthetic operations. METHODS: The aim of this
      review was to highlight the nutritional deficiencies of post-bariatric surgery
      patients as related to planned body contouring surgery. This review was prepared
      by an extensive search of the bariatric surgery literature. RESULTS: The current
      data indicate that many post-bariatric surgery patients have protein-calorie
      malnutrition as well as various vitamins and mineral deficiencies that may limit
      optimal health and healing. CONCLUSIONS: It is essential that those plastic
      surgeons who treat post-bariatric surgery patients are aware of these nutritional
      deficiencies, which can be minimized by adhering to eating guidelines and
      supplemental prescriptions. Although there are many studies documenting
      relationships between malnutrition and poor wound healing, the optimal nutrient
      intake in the post-bariatric surgery state to promote wound healing is unknown.
      It is, however, clear that proteins, vitamin A, vitamin C, arginine, glutamine,
      zinc, and selenium have significant beneficial effects on wound healing and
      optimizing the immune system.

PMID- 18626381
TI  - Sources of processed lipoaspirate cells: influence of donor site on cell
      concentration.
AB  - BACKGROUND: Recently, adipose tissue harvested by liposuction has been identified
      as a source of processed lipoaspirate cells. The aim of this study was to
      determine the concentration of processed lipoaspirate cells in adipose tissue
      obtained by liposuction from different harvest areas in women. METHODS: A
      prospective cross-sectional study was conducted in 25 women in whom liposuction
      in four or more different zones in the same procedure was indicated. After
      selective liposuction, the material was sent to the laboratory, where it was
      processed for extraction of processed lipoaspirate cells, which were separated
      from the adipose tissue, quantified, and characterized through determination of c
      kit expression. The following harvest regions were evaluated: upper abdomen,
      lower abdomen, trochanteric region, inner thigh, knee, and flank. The cell
      concentration obtained at each site was compared by analysis of variance for
      mixed models. RESULTS: A significant difference was found for cell concentration
      obtained at the different harvest sites. The cell concentration in the lower
      abdomen was greater than in other areas, but no significant difference was found
      in relation to the inner thigh. CONCLUSIONS: The lower abdomen and the inner
      thigh may have higher processed lipoaspirate cell concentrations. These sites may
      turn out to be better sources of adult mesenchymal stem cells.

PMID- 18626382
TI  - Discussion: Sources of processed lipoaspirate cells: influence of donor site on
      cell concentration.

PMID- 18626383
TI  - Medial thigh lift.

PMID- 18626384
TI  - Management of a complex scalp defect.

PMID- 18626385
TI  - Discussion: Management of a complex scalp defect.

PMID- 18626386
TI  - Gain without pain: the dawn of elective surgery.

PMID- 18626387
TI  - 360-degree evaluations of plastic surgery resident accreditation council for
      graduate medical education competencies: experience using a short form.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education has asked
      training programs to develop methods to evaluate resident performance, using
      competencies essential for outcomes. METHODS: A two-page form was completed by 12
      surgeons and 28 nurses and clinical staff directly involved in plastic surgery
      patient care (n = 40), evaluating University of Kentucky plastic surgery
      residents at each level of training (n = 6). There were eight groups of health
      care professionals among the 40. Six Accreditation Council for Graduate Medical
      Education competencies were rated, with technical/operative skills added as a
      subset of patient care. Hierarchical cluster analysis was used to determine
      similarity of rating profiles of the rating groups; Kruskal-Wallis analysis of
      variance delineated the way in which the participants used the competencies to
      make their selections by asking them whether they would choose the resident for
      future surgical care. RESULTS: Rating profiles revealed two clusters of raters.
      In one cluster were nurses assigned to an ambulatory surgery center, faculty,
      residents, and an intern (the surgeons' cluster; n = 15); in the second cluster
      were other nurses and clinical staff (nurses' cluster; n = 25). The nurses'
      cluster was found to rate residents more positively, and the surgeons' cluster
      more often cited areas for improvement. Specific competencies deemed important to
      each group were identified. CONCLUSIONS: Resident performance is rated
      differently by health care professionals, in two distinct groups. Based on this
      clustered arrangement, the resident is able quarterly to enjoy two, independent,
      formative assessments, potentially over 6 years of integrated training.

PMID- 18626388
TI  - Discussion: 360-Degree evaluations of plastic surgery resident accreditation
      council for graduate medical education competencies: experience using a short
      form.

PMID- 18626389
TI  - The use of modified sutures in plastic surgery.
AB  - SUMMARY: Modified sutures have been developed and are currently being used in
      closed and open facial rejuvenation procedures. In addition, these sutures have
      applications in body contouring procedures and wound closure. The indications and
      efficacy of these sutures continue to evolve.

PMID- 18626390
TI  - What if the world had 100 people? Counting our blessings in a quantum world.

PMID- 18626391
TI  - Reoperations as a benchmark: the rhetoric, the logic, and the patient.

PMID- 18626394
TI  - Necrotizing dermohypodermitis or fasciitis?

PMID- 18626395
TI  - Management of ear keloids.

PMID- 18626397
TI  - Supraclavicular flaps for the reconstruction of neck scar contractures.

PMID- 18626400
TI  - Regarding true lambdoid synostosis: long-term results of surgical and
      conservative therapy.

PMID- 18626401
TI  - Midterm follow-up of midface distraction.

PMID- 18626402
TI  - Practical guidelines for repair of partial mastectomy defects using the breast
      reduction technique in patients undergoing breast conservation therapy.

PMID- 18626404
TI  - Decreasing the expression of LFA-1 and ICAM-1 as the major mechanism for the
      protective effect of erythropoietin on ischemia-reperfusion injury.

PMID- 18626406
TI  - Virginal breast hypertrophy in the adult.

PMID- 18626408
TI  - Lipoaspirated stem cells may not have been placed in ischemic tissue.

PMID- 18626409
TI  - Treatment of keloids with itraconazole.

PMID- 18626411
TI  - A prefabricated, tissue-engineered integra free flap.

PMID- 18626412
TI  - Two easy and simple modifications when using a distally based sural flap to
      reduce the risk of venous congestion.

PMID- 18626415
TI  - Surgical management of retinal capillary hemangioblastoma associated with retinal
      detachment.

PMID- 18626414
TI  - Earlier age at menopause, work, and tobacco smoke exposure.
AB  - OBJECTIVE: Earlier age at menopause onset has been associated with increased all
      cause, cardiovascular, and cancer mortality risks. The risk of earlier age at
      menopause associated with primary and secondary tobacco smoke exposure was
      assessed. DESIGN: This was a cross-sectional study using a nationally
      representative sample of US women. A total of 7,596 women (representing an
      estimated 79 million US women) from the National Health and Nutrition Examination
      Survey III were asked time since last menstrual period, occupation, and tobacco
      use (including home and workplace second-hand smoke [SHS] exposure). Blood
      cotinine and follicle-stimulating hormone levels were assessed. Logistic
      regressions for the odds of earlier age at menopause, stratified on
      race/ethnicity in women 25 to 50 years of age and adjusted for survey design,
      were controlled for age, body mass index, education, tobacco smoke exposure, and
      occupation. RESULTS: Among 5,029 US women older than 25 years with complete data,
      earlier age at menopause was found among all smokers and among service and
      manufacturing industry sector workers. Among women age 25 to 50 years, there was
      an increased risk of earlier age at menopause with both primary smoking and SHS
      exposure, particularly among black women. CONCLUSIONS: Primary tobacco use and
      SHS exposure were associated with increased odds of earlier age at menopause in a
      representative sample of US women. Earlier age at menopause was found for some
      women worker groups with greater potential occupational SHS exposure. Thus,
      control of SHS exposure in the workplace may decrease the risk of mortality and
      morbidity associated with earlier age at menopause in US women workers.

PMID- 18626417
TI  - Macular hole closure with triamcinolone-assisted internal limiting membrane
      peeling.
AB  - PURPOSE: To evaluate the anatomic and visual outcomes of patients treated with
      triamcinolone-assisted internal membrane peeling for macular hole. METHODS: A
      retrospective chart review of 37 consecutive cases done by a single vitreoretinal
      surgeon for idiopathic macular hole. All surgery involved triamcinolone-assisted
      internal limiting membrane peeling. All patients had at least 3-month follow-up.
      Main outcome measures included anatomic macular hole closure, visual acuity, and
      operative complications. RESULTS: Mean follow-up was 11 months (range, 3-56
      months). Anatomic macular hole closure was achieved in 36 eyes (97%). Mean
      overall preoperative visual acuity was 20/150 and final acuity was 20/63 (P <
      0.0001). Nineteen eyes (51%) had best corrected visual acuity at most recent
      postoperative visit of > or =20/50. There were no postoperative complications.
      CONCLUSIONS: Triamcinolone-assisted internal limiting membrane peel is an
      effective surgical technique in macular hole surgery. Use of triamcinolone
      acetonide did not adversely impact macular hole closure. Anatomic closure rates
      and visual outcomes compared favorably with published literature on macular hole
      surgery.

PMID- 18626416
TI  - Recurrent choroidal neovascularization after macular translocation surgery with
      360-degree peripheral retinectomy.
AB  - PURPOSE: To evaluate the pattern of age-related macular degeneration in the new
      foveal location after macular translocation surgery with 360 degree peripheral
      retinectomy for neovascular age-related macular degeneration. METHODS: Clinical
      data, fundus photos, and fluorescein angiograms of patients in the Duke Macular
      Translocation Study were reviewed with 2-year follow-up data. RESULTS: With 56
      patients completing follow-up, no patient developed de novo choroidal
      neovascularization (CNV), geographic atrophy, or drusen in the new subfoveal
      retinal pigment epithelium bed. By 2 years, 14 patients (25%) developed recurrent
      CNV and 13 of these 14 recurrences clearly arose from the old CNV bed. Of the 13
      recurrences clearly arising from the old bed, 12 of them had recurrent CNV that
      involved the margin of the bed closest to the repositioned fovea. Smokers were
      5.3 times (95% confidence interval: 1.2-24) more likely to develop recurrent CNV
      over 2 years. Despite treatment, median visual acuity for the 14 eyes with
      recurrent CNV was 20/200 compared with 20/80 in eyes without recurrence.
      CONCLUSIONS: Findings in this study support the hypotheses that the development
      of CNV occurs via a signaling mechanism from the fovea.

PMID- 18626418
TI  - Retinal toxicity of commercially available intravitreal ketorolac in albino
      rabbits.
AB  - PURPOSE: To determine whether intravitreal injection of a commercially available
      ketorolac tromethamine preparation causes retinal toxicity in albino rabbits.
      METHODS: Nine albino rabbits were injected intravitreally with ketorolac
      tromethamine (3 mg; 0.1 mL) in one eye and saline (0.1 mL) in the fellow eye. Six
      of the rabbits received a single injection of ketorolac, and the other three
      rabbits underwent biweekly injection for a total of four injections.
      Electroretinography testing was performed on both eyes at different time
      intervals during 4 weeks of follow-up in the single injection group, and during
      12 weeks of follow-up in the multiple injection group. Visual evoked potentials
      were recorded from each rabbit using monocular and binocular stimulation at the
      end of the follow-up period. Animals were then killed, and the retinas were
      prepared for morphologic examination at the light microscope level and for
      immunostaining for glial fibrillary acidic protein, as a marker of retinal
      damage. RESULTS: The electroretinography responses from the control and
      experimental eyes were similar throughout the follow-up period in all rabbits of
      both experimental groups. There were no differences in the flash visual evoked
      potential responses between experimental and control eyes in the single injection
      group, while in the repeated injection group, statistically significant
      differences were found. Light microscopy did not identify significant histologic
      differences between the retinas from control and experimental eyes after a single
      dose. However, after repeated dosing, two of three eyes showed histologic
      evidence of local toxicity. Immunocytochemical analysis showed no glial
      fibrillary acidic protein staining in Muller (glial) cells throughout the retina
      in the single injection group. Slight glial fibrillary acidic protein staining
      was detected in only one of the three retinas from rabbits in the repeated
      injection group. CONCLUSIONS: Commercially available ketorolac tromethamine was
      found to be toxic to the retinas of albino rabbits following multiple
      intravitreal injections at a dose of 3 mg while no electrophysiologic toxicity
      was found. Therefore, the use of commercially available ketorolac containing
      alcohol, for intravitreal injection is not recommended.

PMID- 18626419
TI  - 23-gauge vitrectomy in 100 eyes: short-term visual outcomes and complications.
AB  - PURPOSE: To report the short-term outcomes and complications of patients
      undergoing 23-gauge transconjunctival sutureless pars plana vitrectomy. METHODS:
      Retrospective, consecutive, noncomparative case series in which 100 eyes of 100
      patients underwent elective 23-gauge pars plana vitrectomy for a variety of
      surgical indications. All patients were examined on postoperative day 1 and then
      approximately 1 and 4 weeks later. Demographic and ophthalmic data were recorded.
      RESULTS: Fifty-two men and 48 women (mean age = 65 years) were observed for a
      mean of 26 weeks. Mean preoperative visual acuity was 20/842 and mean final
      postoperative visual acuity was 20/429. Postoperative visual acuity improved in
      68% of patients, worsened in 16%, and remained unchanged in 16%. Mean
      preoperative intraocular pressure was 15 mmHg and mean postoperative intraocular
      pressure at final visit was 14 mmHg. No sutures were required to close
      sclerotomies and no intraoperative complications were observed, though one eye
      required conversion to 20-gauge pars plana vitrectomy during silicone oil
      removal. Postoperative complications included retinal detachment, cataract
      progression, vitreous hemorrhage, persistent macular hole, new macular hole,
      phthisis, posterior capsular opacification, and severe chemosis. CONCLUSIONS:
      Twenty-three-gauge pars plana vitrectomy demonstrates short-term visual outcomes
      and complication rates that are comparable to those reported with 20- and 25
      gauge systems.

PMID- 18626420
TI  - Fixation and removal of dislocated lens nuclei with the shielded bullet pick.

PMID- 18626422
TI  - Correlation of fundus autofluorescence with fluorescein and indocyanine green
      angiography in choroidal melanocytic lesions.
AB  - PURPOSE: To correlate fundus autofluorescence (FAF) patterns with
      fluorescein/indocyanine green angiographic (FA/ICGA) features in choroidal
      melanocytic lesions. METHODS: Retrospective chart review of 30 consecutive
      patients with choroidal nevi and melanoma who underwent FAF photography and
      FA/ICGA. The FAF pattern was classified as patchy or diffuse. The FA images were
      evaluated at the arterial, early venous, late venous, midphase, and late phases.
      The ICGA images were evaluated at the early and midlate phase. The fluorescence
      within the tumor was classified as hyperfluorescent, pinpoint hyperfluorescent,
      isofluorescent, or hypofluorescent with respect to the surrounding retina or
      choroid. Statistical analysis was performed using two sample t test for
      continuous data. For categorical or ordinal data, Pearson chi-square or Fisher's
      exact test was used depending on the sample size being studied. RESULTS: Nineteen
      of 30 tumors (63.3%) were choroidal melanoma and 11 (36.7%) were choroidal nevus.
      Thirteen choroidal melanomas had a diffuse FAF pattern. Six choroidal melanomas
      and 11 choroidal nevi had a patchy FAF pattern. The diffuse FAF pattern was
      significantly associated with the clinical diagnosis of choroidal melanoma versus
      choroidal nevus (P = 0.00001), increased tumor thickness (P = 0.00001), and
      increased tumor base diameter (P = 0.001), partially pigmented or amelanotic
      versus pigmented lesion color (P = 0.006), early venous hyperfluorescence on FA
      (P = 0.015), and late hyperfluorescence on FA (P = 0.018). CONCLUSION: Diffuse
      FAF is more often associated with larger choroidal melanomas as well as early
      venous and late hyperfluorescence on FA angiography.

PMID- 18626423
TI  - Intravitreal triamcinolone acetonide injection at the end of vitrectomy for
      diabetic vitreous hemorrhage: a randomized, clinical trial.
AB  - PURPOSE: To evaluate the clinical outcome and complications of intravitreal
      injections of triamcinolone acetonide in patients undergoing pars plana
      vitrectomy for treatment of diabetic nonclearing vitreous hemorrhage. PATIENTS
      AND METHODS: This prospective, randomized clinical trial study included 72
      consecutive patients (72 eyes) who underwent pars plana vitrectomy for treatment
      of diabetic nonclearing vitreous hemorrhage. 38 patients received an intravitreal
      injection of 4 mg (0.1 cc) of triamcinolone acetonide at the end of surgery. Main
      outcome measures were rate of recurrent early vitreous hemorrhage, reoperation,
      intraocular pressure, visual acuity, and incidence of cataract formation. Mean
      follow-up time was 6 months. RESULTS: Rate of early rebleeding and reoperation
      were lower in patients taking intravitreal triamcinolone (P = 0.003 and 0.03,
      respectively). Visual acuity 6 months after operation was better in study group
      (P < 0.001). Mean intraocular pressure was higher 1 day and 1 week after
      procedure in study group compared with control group (P < 0.001 and 0.002,
      respectively); however, in other times its differences were not significant. No
      significant difference in rate of nuclear sclerosis and cortical cataract
      formation and other complication was noted between the two groups. However, there
      was a significantly increased rate of posterior subcapsular progression in a dose
      dependent manner in the study group versus control (P = 0.011). CONCLUSION: The
      present clinical study suggests that intravitreal injection of triamcinolone
      acetonide is effective in the prevention of rebleeding in eyes undergoing pars
      plana vitrectomy for treatment of diabetic vitreous hemorrhage.

PMID- 18626426
TI  - The role of microRNAs in primary liver cancer.
AB  - Small RNA molecules such as microRNAs, for many years considered to be
      superfluous genomic material, are now known to play important regulatory roles in
      apoptosis, cell proliferation and differentiation, angiogenesis and thus in
      carcinogenesis. Primary liver carcinomas such as hepatocellular carcinomas,
      cholangiocarcinomas and mixed variants show a rising incidence with high
      mortality among affected patients but lack effective targeted therapies except
      the new multiple kinase inhibitor Sorafenib. This review elucidates the recent
      contributions of miRNA gene expression analyses to a better understanding of the
      complex molecular interactions in liver carcinogenesis and highlights their
      future promise to provide novel tools for improved diagnostics, more accurate
      prognostic assessment and tailored molecular therapies in liver cancer.

PMID- 18626427
TI  - The natural course of HCV infection and the need for treatment.
AB  - Nowadays, hepatitis C infection has been identified as the main cause of chronic
      liver disease, including cirrhosis and hepatocellular carcinoma in Western
      Countries. However, despite its large diffusion (with more than 150 million of
      people infected world-wide), the lack of symptoms during the acute phase,
      together with the indolent course of the disease over time, hampers the
      difficulties to assess the natural history of the disease, which still remains an
      interesting clinical dilemma. This complexity can also be argued from the large
      heterogeneity of disease complication's rate observed when different
      methodological approaches were used (retrospective cohort studies, prospective
      cohort studies, retrospective-prospective cohort studies). Moreover, the
      progression of the disease could also be dramatically affected by many variables
      related to the host, the virus and the environment. Finally, in the last few
      years, the long-term outcome of the infected subjects, has been deeply modified
      by the use of efficacy antiviral therapy, as shown by the better survival
      observed in patients who had achieved a sustained virological response after
      interferon treatment.

PMID- 18626428
TI  - Intestinal flora, probiotics, and cirrhosis.
AB  - Intestinal microflora constitutes a symbiotic ecosystem in permanent equilibrium,
      composed mainly of anaerobic bacteria. However, such equilibrium may be altered
      by daily conditions as drug use or pathologies interfering with intestinal
      physiology, generating an unfavorable environment for the organism. Besides,
      there are factors which may cause alterations in the intestinal wall, creating
      the conditions for translocation or permeation of substances or bacteria. In
      cirrhotic patients, there are many conditions that combine to alter the amount
      and populations of intestinal bacteria, as well as the functional capacity of the
      intestinal wall to prevent the permeation of substances and bacteria. Nowadays,
      numerous complications associated with cirrhosis have been identified, where such
      mechanisms could play an important role. There is evidence that some probiotic
      microorganisms could restore the microbiologic and immunologic equilibrium in the
      intestinal wall in cirrhotic patients and help in the treatment of complications
      due to cirrhosis. This article has the objective to review the interactions
      between intestinal flora, gut permeability, and the actual role of probiotics in
      the field of cirrhotic patients.

PMID- 18626429
TI  - Hepatitis B virus and hepatocarcinogenesis.
AB  - Hepatitis B viral (HBV) infection is the commonest cause of hepatocellular
      carcinoma. HBV DNA is the most important predictor of hepatocarcinogenesis in HB
      surface antigen positive patients. We reviewed the mechanism of
      hepatocarcinogenesis on molecular level with a special emphasis on the role of X
      protein. Hepatitis B X-protein communicates with host targets and disturbs
      cellular functions including cell cycle regulation, apoptosis, signalling,
      transcriptional regulation, encoding of cytoskeleton, cell adhesion molecules,
      oncogenes and tumour suppressor genes.

PMID- 18626430
TI  - Black bean extract ameliorates liver fibrosis in rats with CCl4-induced injury.
AB  - We assessed the anti-fibrotic effects of methanolic black bean extract
      antioxidants in a carbon tetrachloride (CCl4) liver injury model in rats.
      Experimentally intoxicated animals received CCl4 for eight weeks, the reference
      and test groups received daily intragastric quercetin or daily intragastric black
      bean extract. Liver fibrosis was assessed and quantified using morphometric
      analysis. Expression of fibrosis related genes was measured by real time RT-PCR.
      Qualitative and quantitative histological analysis showed that administration of
      70 mg/kg b.w. of black bean extract reduced hepatic fibrosis index by 18%
      compared to positive controls (P 0.006), as a result of a decrease in type I
      (44.3% less, P 0.03) and type IV (68.9% less, P 0.049) collagen gene expression
      compared to CCl4-injured and Quercetin treated rats. In conclusion, we provide
      evidence that this methanol black bean extract ameliorates liver fibrosis and
      types I and IV collagen gene expression, in the animal model used. PRACTICAL
      APPLICATIONS: The compounds contained in this black bean extract exhibited strong
      antifibrotic effects in the CCl4 chronic liver injury model used; considering
      that this compounds are contained in a leguminous that has been used in human
      diet for a long time, their toxic potential should be very low, and this
      characteristic should favor their potential use in some other chronic or
      degenerative states that include an increase in inflammation and oxidative burst
      in their pathogenesis. Another possible application of this kind of extract could
      be its use as an antimicrobial or even antiparasitic therapeutic agent, although
      it is purely speculative.

PMID- 18626431
TI  - Influence of extrahepatic viral infection on the natural history of hepatitis C.
AB  - HCV is primarily hepatotropic, but there is mounting evidence pointing to
      infection and replication of extrahepatic sites. Here we evaluated the occurrence
      of HCV infection of peripheral blood mononuclear cells (PBMC) and explored the
      possible association between viral extrahepatic infection and the natural history
      of the disease. Forty seven Chilean, HCV infected, treatment naive patients were
      included in the study. HCV RNA was isolated from plasma and PBMC and subsequently
      reverse transcribed, amplified and sequenced. Most patients harbored HCV 1b
      genotype and the most common route of infection showed to be blood transfusion.
      HCV RNA was readily detected in PBMCs of 34 out of the 47 patients (72%). We
      report that HCV sequences found in PBMC differ from those in plasma of the same
      subjects strongly suggesting HCV compartmentalization. In addition, we found that
      patients with detectable HCV RNA in PBMC had a tendency for being more likely
      cirrhotic [OR 3.8 (95% CI: 0.98 to 14)]. In conclusion, this study provides
      further arguments for the existence of HCV infection of extrahepatic sites and
      suggests that extrahepatic infection could be a factor influencing the natural
      history of the disease.

PMID- 18626432
TI  - Genotyping of hepatitis C virus (HCV) in infected patients from Northeast Mexico.
AB  - Information about HCV genotypes in infected patients from different regions of
      Mexico is limited. OBJECTIVE: To determine the prevalence of HCV genotypes in a
      group of HCV infected patients who attended a third level Hospital in Northeast
      of Mexico. METHODS: Genotyping analysis was performed using the InnoLiPA-HCV
      genotype assay in 147 patients (65 males and 82 females, mean age 44 +/- 12
      years) with positive anti-HCV antibodies and detectable HCV-RNA levels. RESULTS:
      Infected individuals were more likely to be female (56%). Histological data
      showed that 63% of the patients had chronic hepatitis, while the remainder
      presented cirrhosis (37%). The most frequent HCV genotype was 1 (73%). We found
      the following distribution: genotype 1 (2.7%), 1a (28.6%), 1b (37.4%), 1a/1b
      (4.1%), 2a (1.4%), 2b (8.8%), 2c (0.7%), 2a/2c (2.7%), 3 (2%), 3a (10.2%), 4
      (0.7%) and 4c (0.7%). The most frequent associated risk factor was blood
      transfusion (72.5%). CONCLUSION: Prevalence of HCV genotypes in the Northeast of
      Mexico is similar to those reported previously in other Mexican regions and the
      most frequent risk factor continues being blood transfusion.

PMID- 18626433
TI  - Impact of diabetes mellitus on outcome of HCC.
AB  - BACKGROUND: Diabetes mellitus (DM) is recently identified risk factor for
      development and progression of chronic liver disease as well as hepatocellular
      carcinoma (HCC). We planned a prospective analysis to identify impact of DM in
      Indian patients with HCC. METHODS: During last 10 years, 160 consecutive patients
      of HCC were evaluated. Demographic profile like age of presentation, clinical
      features, etiology of HCC, tumor size at presentation, management and ultimate
      outcome was compared diabetic with non-diabetic HCC patients. RESULTS: During
      last 10 years, 160 consecutive patients of HCC were evaluated (Mean age = 59.6 +/
      12.9 years, sex ratio (M: F) = 5.4: 1). Etiology for HCC were hepatitis B in 45
      (28.2%), hepatitis C in 18 (11.3%), alcohol in 27 (16.8%), alcohol with hepatitis
      B in 12 (7.5%), alcohol with hepatitis C in 1 (0.6%), non-alcoholic
      steatohepatitis in 4 (2.5%) and cryptogenic in 53 (33.2%) patients. Patients of
      HCC with DM (group-A, n =46, age = 62.6 +/- 9.5 years, sex (M: F) = 6.6:1) were
      compared with patient of HCC without DM (group-B, n =114, age = 66.7 +/- 13.7
      years, sex (M: F) = 5.4:1). Duration of diabetes in group-A was 7.6 +/- 3.2
      years. Patients in group-A had more advanced HCC (size of lesion > 5 cm and >3
      lesions of 3 cm or more diameter, portal vein thrombosis or intra-hepatic bile
      duct involvement) than group-B [34 (73.9%) vs 72 (54.3%)]. Mortality with in one
      year was significantly more in group-A compared to group-B [36 (78.2%) vs 56
      (49.1%)]. CONCLUSION: DM is associated with more advanced lesion and poor outcome
      in patient with HCC.

PMID- 18626434
TI  - Prevalence of hepatitis B and C seropositivity in a Nigerian cohort of HIV
      infected patients.
AB  - INTRODUCTION: The clinical and public health implications of the convergence of
      the human immunodeficiency virus (HIV) epidemic and chronic viral hepatitis in
      sub-Saharan Africa are poorly understood. This study was designed to determine
      the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV), and
      the impact of co-infection on baseline serum alanine transaminase (ALT), CD4+ T
      lymphocyte (CD4) count, and plasma HIV-RNA (viral load) in a cohort of HIV
      infected Nigerians. METHODS: A retrospective study was conducted, on eligible
      treatment-naive patients who presented between August 2004 and February 2007 to
      the University College Hospital (UCH), Ibadan, Nigeria. Demographic data and pre
      treatment laboratory results (hepatitis B surface antigen (HBsAg), HCV antibodies
      (anti-HCV), ALT, CD4 count and viral load) were retrieved from the medical
      records. Fisher's exact, two sample t-tests, and the Wilcoxon rank sum tests were
      used to compare groups. A logistic regression model was fitted to explore
      characteristics associated with co-infection status. RESULTS: A total of 1779 HIV
      infected patients (male: female ratio, 1:2) met inclusion criteria. HBsAg was
      present in 11.9%, anti-HCV in 4.8% and both markers in 1%. HBsAg was more common
      among males than females (15.4% vs 10.1%, respectively p = 0.001) while anti-HCV
      was detected in a similar proportion of males and females (5.3% versus 4.6%,
      respectively p = 0.559). HIV-infected patients with anti-HCV alone had a lower
      mean baseline CD4 count compared to those without anti-HCV or HBsAg (197
      cells/mm3 vs 247 cells/mm3, respectively p = 0.008). Serum ALT was higher among
      patients with HBsAg compared to those without HBsAg or anti-HCV (43 International
      Units (IU) vs. 39 IU, respectively p = 0.015). Male gender was associated with
      HBV co-infection on logistic regression (OR1.786; 95% CI, 1.306-2.443; p <
      0.005). CONCLUSION: More HIV-infected females than males presented for care in
      this cohort. We identified a relatively high prevalence of HBV and HCV co
      infection in general, and a higher rate of HBV co-infection among males than
      females. Pre-treatment CD4 count was significantly lower among those with HCV co
      infection, while ALT was slightly higher among those with HBV co-infection.
      Triple infection with HIV, HBV and HCV was present in a small but significant
      proportion of patients. These findings underscore the importance of testing for
      HBV and HCV in all HIV-infected persons in our setting.

PMID- 18626435
TI  - Clinical update on non-alcoholic fatty liver disease and steatohepatitis.

PMID- 18626436
TI  - Fanconi-Bickel syndrome--two cases report.
AB  - A one year eight month old male child and his nine month old female sibling were
      presented with Growth retardation, abdominal distension, doll-like faces,
      hepatomegaly, phosphaturia, proximal renal tubular dysfunction. The elder sibling
      also presented with glucosuria, hyperglycemia, hypoinsulinemia. The younger one
      later presented with galactosemia. Biopsy of liver on these two patients revealed
      the accumulation of glycogen in hepatocytes.

PMID- 18626437
TI  - Intraductal oncocytic papillary neoplasm of the liver: case and review of a rare
      variant.
AB  - Intrahepatic cholangiocarcinoma (ICCA) comprises 10% of all cholangiocarcinoma
      (CCA). It can be divided into three macroscopic subtypes, the least common of
      which is characterized by intraductal growth and believed to be more amenable to
      good outcomes with surgical resection compared to other ICCA. Recently, the rare
      finding of oncocytic differentiation has been described in this subtype and
      termed <<intraductal oncocytic papillary neoplasm>> (IOPN), but it remains
      unclear if the presence of oncocytes confers a different tumor behavior. We
      present the eighth reported case of IOPN, which to our knowledge, is the first
      such case that, due to its location and vascular compromise, required orthotopic
      liver transplantation (OLT). This case adds to the little that is known about the
      behavior of IOPN and supports the observation that resection, or OLT when
      resection is not possible, is a valid treatment option.

PMID- 18626438
TI  - Giant hydatid liver cyst. Management of residual cavity.
AB  - The management of the residual cavity during surgical intervention for giant
      hydatid liver cysts is often a challenging problem. Herein, is described the case
      of a 55-year-old female patient who was diagnosed with a giant hydatid cyst
      occupying almost the entire left lobe of the liver. After partial cystectomy, the
      residual cavity was managed by combination of suture obliteration with
      omentoplasty. The patient had an uneventful postoperative course and was
      discharged eight days later. The clinical presentation, diagnostic work-up and
      surgical management of the patient are discussed, along with a review of the
      literature.

PMID- 18626439
TI  - Autoimmune hepatitis induced by the prolonged hepatitis A virus infection.
AB  - Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in the
      world. Rarely, acute infection may persist for a long time. Autoimmune hepatitis
      (AIH) may provide anti-HAV IgM positivity detection for a prolonged time. On the
      other hand, HAV as an infectious agent may also trigger AIH. Here we presented a
      case which seemed like a simple acute viral hepatitis A infection at the
      beginning but turned out to be an AIH according to the International Autoimmune
      Hepatitis Group's system. A 21-year-old female was diagnosed as symptomatic acute
      HAV infection with anti-HAV IgM positivity and elevated aminotransferase levels.
      The other viral serological tests were negative. On the 6th, 12th and 18th months
      of the follow up, her anti-HAV IgM positivity still continued and transaminase
      levels were also 3 to 7 times high of the upper limit of normal. In addition,
      antinuclear antibody was positive. However, on the 19th month anti-HAV IgM could
      be detected as negative. Liver histology was prominent. The patient had a score
      of 16 according to the International Autoimmune Hepatitis Group's system. She was
      given prednisolone (10 mg/day) and azathioprine (100 mg/day). The
      aminotransferase levels were detected within normal ranges at the end of the
      first month of therapy. She was in remission during follow up for 6 years. In
      conclusion, prolonged HAV infection and AIH may not only trigger each other but
      also deteriorate the liver histology. AIH should be investigated in cases of long
      lasting HAV infection in order to begin the treatment earlier. On the other hand,
      AIH patients should also be vaccinated for both HBV and HAV to avoid more severe
      diseases.

PMID- 18626440
TI  - Amebic liver abscess in a patient with polycystic disease.

PMID- 18626441
TI  - Gallbladder disease in patients with primary sclerosing cholangitis.
AB  - BACKGROUND/AIMS: Gallbladder abnormalities may be part of the spectrum in primary
      sclerosing cholangitis (PSC). The aim of the present study was to evaluate the
      occurrence and prognostic importance of gallbladder abnormalities in patients
      with PSC. METHODS: Presence of gallbladder abnormalities was assessed in 286
      patients with PSC treated at the Liver Unit, Karolinska University Hospital,
      Huddinge, between 1970 and 2005. RESULTS: One or more gallbladder abnormalities
      were found in 41% of the patients. Gallstones were found in 25% and cholecystitis
      in 25%. Cholecystitis among patients with extrahepatic involvement of PSC (30%
      (65/214)) was significantly higher than among those with intrahepatic involvement
      (9% (6/70)) (P<0.0001). A gallbladder mass lesion with a mean size of 21 (+/-9)
      mm (S.D.) was found in 18 (6%) patients, in 56% (10/18) of whom it constituted
      gallbladder carcinoma. In 9 patients without a gallbladder mass lesion,
      histological re-evaluation disclosed epithelial dysplasia of the gallbladder.
      CONCLUSIONS: Gallbladder disease is common in patients with PSC. Dysplasia and
      carcinoma are commonly found in gallbladder epithelium, suggesting that regular
      examination of the gallbladder in PSC patients could be of value for early
      detection of a gallbladder mass lesion. Cholecystectomy is recommended when such
      a lesion is detected, regardless of its size.

PMID- 18626442
TI  - Irrationality of sliding scale insulin therapy.

PMID- 18626443
TI  - Comparison of sputum induction with broncho-alveolar lavage in the diagnosis of
      smear-negative pulmonary tuberculosis.
AB  - Sputum microscopy and AFB-culture being gold standard and a fundamental tool for
      diagnosis of pulmonary tuberculosis (PTB) has got its limitation of low
      sensitivity. Fibreoptic bronchoscopy (FOB) has been widely recommended as the
      diagnostic procedure of choice in smear negative patients. But bronchoscopy is an
      invasive procedure, costly, not readily available in our country and needs
      expertise. Several studies abroad have directly compared the yield of sputum
      induction (SI) with 3% saline (NaCl solution) with Bronchoalveolar lavage (BAL)
      through FOB in smear-negative suspected PTB patients and showed that SI was a low
      cost, safe and well tolerated procedure with equal efficacy to BAL through FOB
      for the diagnosis of PTB in such patients. For the first time a prospective
      comparison was conducted in Bangladesh to see the yield of sputum induction (SI)
      and BAL in 52 selected smear- negative patients of suspected PTB. Each of the
      samples of induced sputum and BAL fluid were examined for AFB by Ziehl-Neelsen's
      method. Samples of both SI and BAL from 20 patients were cultured for AFB in
      Lowenstein-Jensen medium for 6 weeks irrespective of their induced sputum smear
      being positive or negative for AFB. Data were managed and analyzed using computer
      program SPSS version 10.0. Agreement of SI and BAL was tested using Pearson Chi
      square and Kappa test. The results showed that the yield of SI were significantly
      more than that of BAL (p<0.05).The AFB smear results from specimens obtained by
      SI and BAL were in agreement in 75% cases (p=0.02).Statistical analysis of the
      yield of culture results from SI and BAL group with Fishers Exact test showed
      they were in agreement in 90% cases (p=0.0001) and was measured by Kappa test as
      significant (p=0.0004). The sensitivity of AFB-smears in samples from SI and BAL
      were 74% and 58% respectively. The specificity of smear positivity and of culture
      was assumed to be 100%. SI is a safe procedure with considerable diagnostic yield
      and a high agreement with the results of BAL through FOB for the diagnosis of
      PTB. SI offers an alternative or additional approach to the diagnosis of smear
      negative suspected PTB patients and would enhance sensitivity for the diagnosis
      of tuberculosis.

PMID- 18626444
TI  - Epidemiological study of risk factors of stroke and its immediate consequence.
AB  - The study was a cross sectional study conducted among 48 stroke patients in
      Medicine & Neuromedicine department of Mymensingh Medical College & Hospital. The
      objective of the study was to reveal the risk factors and other relevant
      information & immediate outcome of stroke patients. The sample size was 48 who
      were selected purposively and study area was selected for easy access. Study
      period was from 15th May 2007 to 15th July 2007. Forty eight (48) respondents and
      their reliable attendants were interviewed by pre tested structured
      questionnaire. Among 48 stroke patients 60% were male& 40% were female.
      Occupations of the patients were 21% desk job, 15% laborious work, 37% housewife,
      6% businessman &21% in other profession. Age group of respondents were 13% below
      45 years of age, 25% were 45-55 years of age, 29% were 55-65 years of age & 33%
      were over 65 years of age. Among 48 stroke patients 62.5% had 1st attack & others
      had multiple attacks. Among all the stroke patients 37.5% performed physical
      exercise. Forty six percent (46%) patients have family history of Hypertension.
      27% have no family history of Hypertension & 27% have no idea. Sixty six percent
      (66%) patients have suffering from Hypertension, 23% have no history of
      Hypertension & 10% have no idea. Sixty percent (60%) patients had habit of
      Smoking, 40% had no habit of Smoking. 21% patients have family history of
      Diabetes, 48% have no family history of Diabetes & 31% have no idea about family
      history of Diabetes. Complications among stroke patients are 51% have Hemiplegia,
      10% have Paraplegia, 23% have Paresis, 10% have Aphasia & 6% have others
      complications.

PMID- 18626445
TI  - Association of tuberculosis with vasculitis retinae.
AB  - Retinal vasculitis is one of the common causes of blindness among the young adult
      in this subcontinent. Causes of retinal vasculitis are variable and it is one of
      the common ocular manifestations of tuberculosis. This case control study was
      carried out on 45 patients with retinal vasculitis of different age groups. All
      the patients were purposively selected from the department of ophthalmology,
      Bangabandhu Sheikh Mujib Medical University and National Institute of
      Ophthalmology Dhaka. This study reveals that vasculitis retinae is a disease of
      younger age group (68.9%). Mean+/-SD age of cases were 31.84+/-10.82 years. It
      occurs more in male (75.6%) and male female ratio is 3.09:1, single or both eye
      may involve. Retinal vasculitis occurs more in middle socio-economic status
      persons (62.2%). It present with floaters (58.9%), hazy media (60%), vitreous
      haemorrhage (57.8%) and retinal haemorrhage (42.2%). All 45 subjects both cases
      and control groups were tested with Mantoux test. 18(40%) subjects of cases and
      13(28.9%) subjects of control group were found positive Mantoux test. It was
      observed that the association of tuberculosis with vasculitis retinae is not
      statistically significant. As tuberculosis is common in this country, further
      specific and extensive study over a longer period of time is necessary for
      understanding the role of tuberculosis in retinal vasculitis patients.

PMID- 18626446
TI  - Histomorphological study of lymphoid follicle of vermiform appendix.
AB  - The study was done to find out the number of lymphoid follicle of vermiform
      appendix in Bangladeshi people and to increase the knowledge regarding
      variational anatomy in our population. Total 40 fresh appendixes were collected
      for histological study of different age and sex during postmortem examination in
      the autopsy laboratory of Forensic department of Mymensingh Medical College. This
      cross sectional descriptive study was done by convenient sampling technique. For
      convenience of differentiating the number of lymphoid follicle of vermiform
      appendix in relation to age and sex, findings were classified in four groups, up
      to 20 years, 21 to 35 years, 36 to 55 years and 56 to 70 years. In the present
      study the number of lymphoid follicle were highest in group A, mean were (5.40+/
      1.30) and lowest in group D where mean were (1.05+/-0.35). In male mean were 3.16
      and in female mean were 2.86. Diameter of the lymphoid follicle in group A was
      highest (40.14+/-2.66) and lowest in group D (0.24+/-1.35). Number of germinal
      centre are highest in group B (2.20 +/- 0.45) and lowest in group D (0.00 +/-
      0.00).

PMID- 18626447
TI  - Relationship of uterine artery with ureter.
AB  - The study was done to see the relationship of right and left uterine artery with
      corresponding ureter. Their distance from lateral border of uterus and site of
      crossing in relation to internal os in Bangladeshi female were observed. Sixty
      post mortem specimens containing uterus, uterine tube, ureter and surrounding
      structures were collected from cadavers of different age groups and fixed in 10%
      formol saline solution. Gross and fine dissections were carried out to study the
      relationship and distance of uterine artery where it crosses the corresponding
      ureter and the site of crossing in relation to internal os. In the present study
      our findings were compared with those of the standard text books. In this study,
      there were no variations regarding relations of right and left uterine artery
      with corresponding ureter. In all cases of all age groups, ureters were found to
      cross the uterine artery anteriorly on both sides. Site of crossing of uterine
      artery of both sides with ureter at the level of internal os was 50% in 2-12
      years (Group A) 20.45% in 13-45 years (Group B) and 12.50% in 46-80 years (Group
      C) age group. Below the level of the os was found in remaining cases except one
      which crosses above the level of the os in group B. In this study mean distance
      of uterine artery where it crosses the ureter from lateral border of uterus was
      more on right side in all age groups, which was 1.67 cm, 2.30 cm and 2.11 cm in
      age Group A, B & C respectively.

PMID- 18626448
TI  - Serum zinc level in preterm low birth weight babies and its comparison between
      preterm AGA and preterm SGA babies.
AB  - Low birth weight (LBW) is a major child health problem in Bangladesh and
      continuing to great threat to child health and child survival in Bangladesh. LBW
      is a silent emergency but crisis is real and its persistence has profound and
      frightening impact on neonatal mortality. This observational study was conducted
      in Dhaka Shishu Hospital, Dhaka, Bangladesh during July 2004 to June 2005. Serum
      zinc levels were estimated between two groups: group-I preterm AGA (n=50), group
      II preterm SGA (n=50) babies. Blood samples were collected from the study
      population in neonatal unit and serum zinc levels were measured by flame atomic
      absorption spectrophotometry in Atomic Energy Center, Dhaka, Bangladesh. Observed
      data were made comparison among groups by Students 't' test. It was observed
      serum zinc level (60.2+/-15.2) in group I and (62.1+/-12.4) in group II. Serum
      zinc level was in lower limit of normal range in both groups with more lower
      level in preterm AGA babies but their difference was not statistically
      significant (p>0.05). So zinc supplementation may enhance the growth of preterm
      LBW babies in their early months of lives.

PMID- 18626449
TI  - Incidence of typical and atypical hanging among 66 hanging cases.
AB  - Present Study conducted prospectively to find out the position of knot in the
      neck in all hanging cases coming for post mortem examination at Mymensingh
      Medical College Mortuary in the year 2005. Hanging is a process in which the body
      is suspended with a ligature around the neck, which causes constriction of air
      passage preventing exchange of air between atmosphere & alveoli of lungs, leading
      to asphyxia & death. The constriction force is either the weight of the whole
      body or the weight of the head alone. A weight of 2Kg is sufficient for death in
      hanging. According to position of knot hanging is of two types-Typical hanging
      and Atypical hanging. In typical hanging the knot of the ligature should be at
      the nape of the neck and the knot of the ligature at any site other than the nape
      of the neck is Atypical hanging. A total of 557 postmortems were conducted in the
      year 2005 out of which 66 cases were of hanging. Among these, 66 cases (100%)
      position of knot on neck were on center of occiput (Typical hanging) in 14 cases
      (21.21%), on right side in 17 cases (25.75%), on left side in 21 cases (31.81%)
      and on front of neck in 14 cases (21.21%). Total of 52 cases are of Atypical
      hanging. This study suggests that Atypical hanging is more common (78.78%) than
      Typical hanging (21.21%) and more on left side of the neck (31.81%). Study at
      S.P. Medical College and A.G Hospitals, Bikaner in 2004 shows that out of 390
      cases 35 (8.97%) were of hanging. Amongst those 35 cases in 33 cases position of
      knot on nape of the neck in 5 cases (15.15%), right side of neck 15 cases
      (45.45%), left side of neck in 11 cases (33.33%) and front of the neck 2 cases
      (6%). In their study, Typical hanging was found in 15.15% and Atypical hanging
      was in 84.85%; and Maximum on right side of the neck i.e. 45.45%. In both the
      studies Atypical hanging was more common but Maximum was on right side in their
      study and We found maximum on left side.

PMID- 18626450
TI  - Comparison of haematological values among different groups of low birth weight
      babies and normal birth weight babies.
AB  - This prospective cross sectional study was carried out in Bangabandhu Sheikh
      Mujib Medical University (BSMMU), Dhaka. This study was undertaken to compare the
      haematological value (reference range) among Small for gestational age-low birth
      weight (SGA-LBW), Appropriate for gestational age-low birth weight (AGA-LBW) and
      Normal birth weight (NBW) babies. Total 90 (ninety) newborn babies were enrolled
      in this study. They were ultimately divided into three groups as a) Group I (SGA
      LBW), b) Group II (AGA-LBW), c) Group III (NBW). Study period was one year
      (December 2003 to December 2004), Relevant informations were collected from the
      guardian of the babies before inclusion in the study. In group I, 19(63.3%) were
      preterm and 11(36.7%) were term. In group II, 30(100%) were preterm and in group
      III, 30(100%) were term. Mean Hb, and HCT levels were highest in group I (SGA
      LBW) and the value was 17.14+/-1.41 gm/dl (Hb) and 0.51+/-0.04 (HCT)
      respectively. Mean Hb and HCT value were lowest in group II (AGA-LBW) and the
      value was 14.57+/-1.78 gm/dl (Hb) and 0.43+/-0.05 (HCT) respectively. In between
      value was found in group III (NBW) and the value was 16.14+/-1.09 gm/dl (Hb) and
      0.48+/-0.04 (HCT) respectively. Differences were statistically significant. On
      the contrary, MCV Values were highest in group II (AGA-LBW) and the value was
      103.23+/-4.99 (fl). Lowest MCV value was in group III (NBW) and the value was
      98.13+/-3.93 (fl). In between result of MCV value was found in group I (SGA-LBW)
      and the value was 99.27+/-10.73 (fl). Differences were also statistically
      significant. MCH and MCHC level was also highest in group I (SGA-LBW). Difference
      was also statistically significant. No significant differences of TC of WBC and
      platelet counts were not found among different groups. Hb and HCT level had
      significant positive correlation with gestational age. Other parameters had no
      Positive correlation with gestational age.

PMID- 18626451
TI  - Comparative study between clinical and sonographic estimation of fetal weight in
      third trimester of pregnancy and its relationship with actual birth weight.
AB  - This prospective study was undertaken to assess the accuracy of clinical and
      sonographic estimated fetal weight (EFW) in Bangladeshi population. The study
      protocol consisted of achieving clinical followed by sonographic estimated fetal
      weight (uEFW) using Shepard formula and then its correlation with actual birth
      weight (BW). A total of 140 pregnant women participated in this study. The study
      was conducted in the department of Radiology & Imaging and in the department of
      Gynae & Obs., Bangladesh Medical College Hospital (BMCH) from January 2005 to
      December 2005.Maximum number of patients belonged to 26-30 years age group and
      the mean +/-SD age of the study patients was 26.8+/-4.7 years. Maximum number of
      women (41.4%) was primigravida and 24.3% women were second gravida. The mean+/-SD
      gestational age of the patient was 35.9+/-2.8 weeks. We found, clinically EFW was
      3432.1+/-410.1 gm (mean+/-SD) and uEFW was 2715.4+/-509.1gm (mean+/-SD) with
      difference 716.7+/-278.5 gm (mean+/-SD), (P<0.001), which is highly significant.
      Babies who were delivered within 1st week of clinical and sonographic EFW were
      selected and their weights were compared with actual BW. The Pearson correlation
      chi square test and student 't' test were the statistical analysis used. It was
      found that the P value of clinical versus actual BW was <0.05, this was
      significant. P value of sonographic versus actual BW was >0.05, this was not
      significant. Percent error (PE) was found 2+/-7.33% in calculating uEFW from
      actual BW with minimum error -23.9% and maximum error 11.81%. This study
      conducted on Bangladeshi fetus using the Shepard formula showed that the actual
      BW recorded after delivery of the fetus is more close to uEFW than clinically
      EFW.

PMID- 18626452
TI  - Variation between CT scan findings and histological diagnosis of intracranial
      glioma.
AB  - A total of 45 cases were studied to elucidate the variation between CT scan
      findings and histological diagnosis of intracranial glioma. They were operated
      and histopathological examination of all cases was studied. The mean age of the
      patients were 35+/-2.37 years and ranged from 01 to 65 years. The highest
      incidence of glioma was found in age group between 40-50 years. The incidence of
      glioma was more in male 36(80%) in comparison to female 9(20%). The main
      presenting complaints were headache in 42(93.3%), vomiting in 34(75%), limb
      weakness in 28(62.2%) and blurring of vision were in 26(57.8%) patients. Other
      symptoms were convulsion in 29(64.4%) patients and altered consciousness
      24(53.3%) patients. By CT scan, diagnosis was made as informed gliomas in all
      cases. Histopathological examination showed 41(91.1%) cases were gliomas and
      3(6.7%) were meningiomas and 1(2.2%) was brain abscess. So there were little
      variations between CT scan findings and histopathological diagnosis.

PMID- 18626453
TI  - Serum lactate dehydrogenase as a prognostic marker of childhood acute
      lymphoblastic leukemia.
AB  - The estimation of serum lactate dehydrogenase (LDH) is easy, readily available
      and economic. We can assume the prognosis of childhood acute lymphoblastic
      leukemia (ALL) through this measurement. This case control prospective study was
      aimed to evaluate that the level of serum LDH has the prognostic marker of
      childhood ALL. The study was carried out in the Paediatric Haematology and
      Oncology unit, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during
      the period from January to December 2006 on 69 subjects with age ranging from
      birth to 15 years irrespective of sex. The study subjects were grouped into case
      (ALL-44) and control (healthy-25). Serum LDH level were performed in ALL patients
      on admission, day 14 and day 29 of induction and in healthy control when came for
      check up and found healthy. Haematological parameters were performed in ALL
      patients and in healthy control along with the measurement of serum LDH. On
      admission the level of serum LDH was significantly raised in ALL patients than
      healthy control (p<0.001). After induction, serum LDH level were significantly
      decreased at day 14 and day 29 of induction from admission (p<0.001). There was
      significant rise of platelet count were observed at day 29 of induction from
      admission (p<0.001). A significant decrease of peripheral and bone marrow blast
      cell percentages were observed at day 29 of induction from admission (p<0.001).
      The total WBC count was significantly decreased along with serum LDH at day 14
      and day 29 of induction from admission (p<0.001). So, the measurement of serum
      LDH can be accepted as a good and reliable prognostic marker of childhood acute
      lymphoblastic leukemia.

PMID- 18626454
TI  - Comparative study of lung functions in women working in different fibre
      industries.
AB  - A cross sectional work has been done on Bangladeshi females, working in different
      fibre industries, to study the effect of exposure to fibre dust on pulmonary
      functions. The ventilatory capacities were measured by VMI ventilometer in 653
      apparently healthy women (160, 162 and 167 were jute, textile and garment
      industry workers, respectively). For the controls 164 females were recruited who
      never worked in any fibre industry. The observed FVC, FEV1 and PEFR were lower in
      all groups of fibre industry workers than those of the control. Among the
      industry workers, the jute mill workers had the lowest ventilatory capacities and
      garment industry workers had the highest values. The jute and textile mill
      workers had also significantly lower FEV1 and PEFR than those of garment industry
      workers. The FEV1 and PEFR were significantly lower in jute mill workers than
      those of textile ill workers. The low ventilatory capacities were almost
      proportionate with the length of service of the workers. Thus, the present study
      indicates that the fibre dust, on regular exposure for longer duration, may limit
      the lung functions.

PMID- 18626455
TI  - Evaluation of alternative diagnostic techniques for diagnosis of cerebral malaria
      in a tertiary referral hospital in Bangladesh.
AB  - Five alternative techniques for diagnosis of malaria were evaluated in 124
      clinically diagnosed cerebral malaria cases admitted in a tertiary hospital in
      Bangladesh. Clinical diagnosis of cerebral malaria was done by WHO criteria. The
      tests were conventional routine malaria microscopy; prolonged microscopy;
      dipstick antigen capture assay (Para Sight TM-F test); pigments in peripheral
      leucocytes and routine microscopy repeated at 12 hours interval. First four tests
      were done at 0 hours of hospital admission and repeat routine microscopy was
      added at 12 hours interval. Diagnostic capability of the test was 64%, 65%, 69%,
      27% and 63% respectively. None of the tests except pigments in peripheral
      leucocytes was superior at initial evaluation. Only the dipstick test added 5%
      more diagnostic possibility compared with routine microscopy as standard.
      Stratification of diagnostic capability in different ways improved diagnosis 15%
      and 11% in smear negative cases by dipstick and prolonged microscopy
      respectively. It was increased by 50% (5/10 patients) with dipstick test in the
      smear negative patients with history of anti-malarials prior to hospital
      admission.

PMID- 18626456
TI  - Histopathological changes of pancreas in patients with fibrocalculous
      pancreatopathy.
AB  - A total of 20 pancreatic biopsy samples taken from Fibrocalculous Pancreatopathy
      previously known as Fibro Calculus Pancreatic Diabetes (FCPD) patients, a variant
      of Malnutrition Related Diabetes Mellitus (MRDM) or under 30 young diabetes
      attending hepatobiliary, surgical and out patient department of Bangladesh
      Diabetes, Endocrine and Metabolic (BIRDEM) hospital were processed for light
      microscopic examination. Four samples were subjected to Immunohistochemistry
      (IHC) staining using antibodies to T cell marker (CD3), B cell marker (CD20),
      anti apoptotic markers (bcl-2) and tumour suppressor gene marker p53. Light
      microscopic findings and IHC indicate an immune mediated injury of pancreatic
      tissue and increased evidence of apoptosis which possibly results in the
      development of diabetes in these patients.

PMID- 18626457
TI  - Unusual presentation of progressive systemic sclerosis.
AB  - A female 38 years old, housewife, presented to the Department of Dermatology and
      Venereology, Mymensingh Medical College Hospital (MMCH) on 08.04.07 with the
      complaints of i) pain and reduced movement of hand, knee, shoulder and neck
      joints for 1 year and 9 months ii) tightness of skin over face, neck, limbs and
      trunk for 1 year and 6 months iii) patchy depigmentation over same areas for 1
      year and 3 months iv) deformity of hands with flexion contractures for 6 months
      and v) dysphagia to solid food for 3 months. She had no complaints of Raynaud's
      phenomenon. On general examination, she was ill looking, anemic and nutritionally
      poor. Examination of integumentary system showed smooth, shiny, thick, hard and
      hidebound skin with pigmentary alteration of 'salt and pepper' appearance over
      fingers, hands, limbs, face, neck and trunk. Hands appear claw like but more on
      the right side than the left and there were no other obvious changes suggestive
      of digital ischaemia (atrophy, ulceration, scarring, gangrene etc). Face has got
      suggestive features of scleroderma. Examination of the respiratory system showed
      restriction of chest movement and reduced expansibility of chest wall. No other
      abnormality was found on examination of other systems. Laboratory investigations
      showed histopathology typical of scleroderma. X-ray of hands and feet showed
      suggestive changes, lung function test-showed restrictive lung disease. Barium
      swallow x-ray of esophagus in supine position showed mild dilation of lower
      oesophagus. But serology was non-reactive (negative ANA, Negative RA test,
      Negative VDRL). So, she was diagnosed as a case of progressive systemic sclerosis
      (PSS) with some atypicality.

PMID- 18626458
TI  - Optic nerve avulsion following accidental penetrating orbital injury.
AB  - Traumatic enucleation with optic nerve avulsion following accidental penetrating
      orbital injury is a rare phenomenon. A 35 years old young active man was suddenly
      traumatized in his left orbit after falling down on a boat following collision of
      two running boats having no search light in a dark night. The patient was
      examined few hours after the event. The patient presented with severe pain around
      left periorbital region. He never lost consciousness. On examination right eye
      revealed no abnormality. There was left periorbital swelling with blood clots.
      Left eyeball was hanging from the orbit with 20mm portion of optic nerve. Left
      eyeball was suspended with the attachment of superior oblique, superior rectus,
      inferior rectus, lateral rectus muscle. Medial rectus was lacerated and could not
      be traced out. One V shaped lacerated injury over the root of left side of nose
      was noted. One arm of the injury caused full thickness laceration of upper lid
      and other arm entered within orbit with medial bony orbital wall in nasal side
      and periorbita with other structures in temporal side upto apex of the orbit.
      Another lacerated full thickness lower lid injury was also noted. This case was
      managed surgically by removal of the left eyeball with orbital implant.
      Conjunctival injury, upper and lower lid injuries were repaired after proper
      surgical toileting. Ocular prosthesis was given two weeks later to have a good
      cosmetic view. Postoperatively the patient was managed with systemic antibiotics,
      NSAIDS and topical antibiotics. Traumatic enucleation following accidental boat
      collision was not reported yet. Awareness of the passengers, strict maintenance
      of the navigation rules may prevent this type of hazards.

PMID- 18626459
TI  - Giant penoscrotal filariasis.
AB  - A 42 year old male individual having a hugely distended scrotum and barely
      perceptible penis, unable to maintain his livelihood on account of his handicap
      and socially withdrawn for the fear of humiliation, got admitted into the Surgery
      department of Mymensingh Medical College Hospital in August 5, 2007. The person
      had been carrying the so called curse for the last four years. On the basis of
      clinical, serological and haematological examinations, diagnosis was established
      as lymphatic filariasis causing elephantiasis of the scrotum. After assessment
      for operative feasibility, the patient underwent an operation in August 20, 2007
      during which, ligation of both the spermatic cords, excision of the scrotum along
      with the testicles and reposition of the penile shaft into the anterior pelvic
      wall in the subcutaneous plane (Fleying procedure) was performed. The scrotum
      measured about 36 inches in diameter and weighed 40 kgs after excision.
      Histopathological examination of the scrotal skin confirmed the diagnosis. The
      patient was released without any complication, on the 11th post operative day
      after removal of stitches, with indwelling urethral catheter. He was prescribed
      Doxicycline for the next 8 weeks, a drug which has been found to be effective in
      treating filariasis in a number of studies, and acts by killing a symbiotic
      bacteria necessary for the survival of the worm. Follow up after 3 months was
      uneventful.

PMID- 18626460
TI  - Pott's disease in a young child.
AB  - A 16-month-old emaciated, immunized child presented with low-grade fever and
      progressive kyphosis with a right sided para-vertebral abscess for 9 months.
      During this period of illness the child had marked loss of appetite and
      progressive weight loss. There was history of contact with sputum smear positive
      father. A gibbus was present at thoraco-lumbar region with a cold abscess at the
      right side of the gibbus and signs of upper motor neuron lesion were found on
      lower limb examination. Diagnosis was supported by relevant investigations
      including MRI of dorsolumbar spine and treatment was started beforehand with anti
      tubercular drugs. The paravertebral abscess was drained several times and
      antibiotics were used depending upon the results of microbiological study. At the
      same time the patient was advised to wear a modified chest brace for
      immobilization and the management for severe malnutrition was also started
      accordingly. There was significant clinical improvement observed within one month
      of starting treatment.

PMID- 18626461
TI  - Congenital nephrotic syndrome, an uncommon presentation of cytomegalovirus
      infection.
AB  - Cytomegalovirus (CMV) infection is a very rare infection in children as well as
      in infancy. In CMV infection extra renal manifestations in central nervous system
      (CNS), eyes and hematological are prominent and common than renal manifestation.
      We are describing two case reports one at the age of 5 months and another at one
      month with features of both extra renal and renal manifestations of nephritic
      syndrome. Our first case presented with predominant features of CNS
      manifestations like convulsion and spastic monoplegia, sensory type of deafness
      and absence of light reflexes along with nephritic features. Deafness and absence
      of light reflex were confirmed by audiometric and ophthalmological examination
      and brain atrophy was confirmed by CT scan. Our second case had features of
      hypothyroidism along with nephritic features. Hypothyroid status was confirmed by
      elevated serum TSH level and reduced T4 level. In both cases nephritic features
      were confirmed at bed site urine examination by heat coagulation test and other
      relevant investigations. CMV infection was confirmed in both cases by detecting
      anti CMV IgM by ELISA method. Both patients were clinically improved with
      intravenous gangcyclovir therapy. In these two cases reports, clinical,
      serological and therapeutic observation established the causal relationship
      between the CMV infection and nephrotic syndrome.

PMID- 18626462
TI  - A case of renal transplantation.
AB  - A 12-year-old boy was admitted in paediatric nephrology unit of Bangabandhu
      Sheikh Mujib Medical University (BSMMU) with massive proteinuria, hypertension,
      respiratory distress and anaemia and diagnosed as nephrotic syndrome.
      Percutaneous needle biopsy was consistent with diffuse endocapillary
      proliferative glomerulonephritis and initially managed conservatively with
      injection methyl prednisolone, cyclophosphamide, lisinopril etc. without any
      improvement. Living-related renal transplantation was done successfully from
      paternal uncle. Two episodes of acute rejection occurred, one immediately after
      transplantation and another after one month. These were managed with IV methyl
      prednisolone for 3 days. At present, he is on oral prednisolone, cyclosporine,
      azathioprine and antihypertensives with normal haemoglobin and stable serum
      creatinine level (pre-transplant level 12.5mg/dl to post-transplant level
      1.5mg/dl). He has been maintaining his normal life including schooling for last
      few months. It is concluded that a patient with uncommon presentation of
      nephrotic syndrome should be confirmed by renal biopsy and renal transplantation
      may be considered if conservative measures fail.

PMID- 18626463
TI  - Anticholesterol antibody: the way for reduction of hypercholesterolemia.
AB  - Antibodies specific to cholesterol was first reported in 1925. It may develop in
      the body naturally and it is believed that this antibody has a protective role
      against harmful forms of cholesterol, such as LDL & VLDL. An immunoglobulin
      protein, anticholesterol may be found in both circulation as well as digestive
      tract. Many studies have been done on anticholesterol antibody. Our immune system
      may produce anticholesterol antibodies in response to elevated levels of
      cholesterol rich particles, such as LDL & VLDL. It can be induced in animals by
      conjugating or incorporating the cholesterol antigen into a variety of
      structures. Immunization markedly decreases the risk of developing
      atherosclerosis. In comparison to non-tumorous normal subject, the antibody is
      found to be significantly higher in non-small cell lung cancer (NSCLC). Elevated
      anti-cholesterol antibodies might be applicable for the serodiagnosis of NSCLC.
      Some studies showed that LDL immunization induces T-cell dependent antibody
      formation that protects atherosclerosis. Origo Biosciences scientists had
      identified a dietary antibody to cholesterol. This protein, when ingested, binds
      to cholesterol in the human digestive tract and blocks its absorption into the
      bloodstream. These studies may lead to us to realize the importance of
      anticholesterol and to find the way for reduction of hypercholesterolemia and
      thereby reduction of morbidity and mortality.

PMID- 18626464
TI  - Anesthesia for emergency cesarean section.
AB  - Caesarean Section is one of the most common of all surgical procedures. Common
      indications for caesarean section may include foetal distress, Cephalopelvic
      disproportion and failure of labour to progress. Both regional and general
      anesthesia may be employed for caesarean section. Each is relatively safe and
      they have their own advantages and disadvantages. Actual decision to adopt one
      technique over another depends on maternal and foetal status and skill and
      ability of the anesthesiologist to tackle the situation with the aim of patient
      and baby safely. Among these, many of the cases come to the hospital as emergency
      basis. The Anesthesiologists have to face the challenge in providing anesthesia
      for emergency caesarean section, being the last member in the perinatal team. The
      challenge faces the risks in involvement of maternal changes in pregnancy,
      presence of foetal distress and various anesthetic complications arising in
      perioperative period. Still now anesthetic mishaps are considered as the sixth
      most frequent cause of maternal mortality. The use of regional Anesthesia reduced
      the number of deaths at about 80% but deaths involving general anesthesia has not
      decreased and the incidence is 17 times more than the regional anesthesia. Most
      of the deaths or complications are related to the airway management (also failed
      intubation). Better skill and knowledge in physiology, pharmacology and use of
      modern Anesthetic technique is essential to face the problems.

PMID- 18626465
TI  - Drug abuse and addiction.
AB  - Among the social and medical ills of the twentieth century, substance abuse ranks
      as on one of the most devastating and costly. The drug problem today is a major
      global concern including Bangladesh. Almost all addictive drugs over stimulate
      the reward system of the brain, flooding it with the neurotransmitter dopamine.
      That produces euphoria and that heightened pleasure can be so compelling that the
      brain wants that feeling back again and again. However repetitive exposure
      induces widespread adaptive changes in the brain. As a consequence drug use may
      become compulsive. An estimated 4.7% of the global population aged 15 to 64 or
      184 million people, consume illicit drug annually. Heroin use alone is
      responsible for the epidemic number of new cases of HIV/AIDS, Hepatitis and drug
      addicted infant born each year. Department of narcotic control (DNC) in
      Bangladesh reported in June 2008 that about 5 million drug addicts in the country
      & addicts spend at least 17 (Seventeen) billion on drugs per year. Among these
      drug addicts, 91% are young and adolescents population. Heroin is the most widely
      abused drugs in Bangladesh. For geographical reason like India, Pakistan and
      Myanmar; Bangladesh is also an important transit root for internationally
      trafficking of illicit drug. Drug abuse is responsible for decreased job
      productivity and attendance increased health care costs, and escalations of
      domestic violence and violent crimes. Drug addiction is a preventable disease.
      Through scientific advances we now know much more about how exactly drugs work in
      the brain, and we also know that drug addiction can be successfully treated to
      help people stop abusing drugs and resume their productive lives. Most countries
      have legislation designed to criminalize some drugs. To decrease the prevalence
      of this problem in our setting; increase awareness, promoting additional research
      on abused and addictive drugs, and exact implementation of existing laws are
      strongly recommended. We should also deserve renewed attention on prescription
      drug abuse. It is imperative that as a nation we make ourselves aware of the
      consequences associated with drug abuse. Otherwise devastating effects of drug
      will destroy the manpower and economic growth of the country.

PMID- 18626466
TI  - Typhoid Fever.
AB  - Typhoid fever is one of the most common febrile illnesses encountered by the
      physicians in Bangladesh. Diagnosis is not difficult but has lately become a
      challenge due to changed clinical pattern of the disease, lack of adequate
      facilities for blood, stool, urine culture, excessive reliance on nonspecific
      Widal test and non availability of any reliable rapid diagnostic tests. Further,
      the indiscriminate and injudicious use of antibiotics for treating fever in
      undiagnosed febrile illnesses early has created problems to the physicians to
      reach to a diagnosis later on. This has also led to the emergence of high level
      resistance to many of the commonly used antibiotics in our country. Ciprofloxacin
      is often used empirically for treating the disease though there is already a high
      level resistance. In case the organism is in-vitro sensitive to ciprofloxacin but
      resistant to nalidixic acid, a much higher dose of drug is required to maintain
      the MIC which is 10 times higher than usual. Third generation cephalosporins
      (ceftriaxone and cefixime) are still the effective drugs for treating typhoid
      fever. The drug needs to be used in proper dose and duration to prevent emergence
      of resistance. Azithromycin though advocated by many as an alternative to
      ciprofloxacin in resistant cases, has recently lost its credibility due to
      emergence of resistance. We should not rely on Widal test in diagnosing typhoid
      fever. In a suspected case, the patient should not be prescribed any antibiotic
      without sending blood sample for culture sensitivity.

PMID- 18626467
TI  - Classification of renal cell carcinoma based on expression of VEGF and VEGF
      receptors in both tumor cells and endothelial cells.
AB  - Recent development of antiangiogenic therapy for renal cell carcinoma (RCC) has
      significantly improved the treatment of these often refractory tumors. However,
      not all patients respond to therapy and assays for predicting outcome are needed.
      As a first step, we analyzed a retrospective cohort of tumors and assessed the
      ability of VEGF and VEGF receptors (VEGF-R1, -R2 and -R3) to classify tumors. We
      analyzed tissue microarrays containing 330 RCCs using a novel method of automated
      quantitative analysis of VEGF and VEGF-R expression by fluorescent
      immunohistochemistry. Expression of markers was separately quantified within
      three tissue components: tumor cells, endothelial cells and adjacent normal
      epithelium. VEGF and VEGF receptors were tightly coexpressed both within tumors
      and within adjacent normal cells (all P-values <0.001). Tumor cell expression of
      VEGF-R1 and -R2 was strongly and inversely correlated with vessel area
      (P<0.0001). Unsupervised hierarchical clustering classified tumors by coordinated
      expression of VEGF and VEGF-Rs. The distribution of clear cell and papillary
      tumors was not significantly different between clusters. Clusters with high
      expression of VEGF and VEGF-Rs in the tumor cells exhibited poor survival when
      compared with the other clusters on uni- and multivariable analysis. VEGF and
      VEGF receptors exhibit a complex pattern of coordinated expression in RCC.
      Clustering tumors by VEGF and VEGF-R in tissue components demonstrates distinct
      tumor phenotypes with different outcomes, and may provide a means for determining
      which tumors will respond to what antiangiogenic therapies.

PMID- 18626468
TI  - Interleukin-4 induces the activation and collagen production of cultured human
      intrahepatic fibroblasts via the STAT-6 pathway.
AB  - Interleukin-4 (IL-4) is overexpressed in liver grafts in a context of severe
      recurrent hepatitis C, during which the development of fibrosis is dramatically
      accelerated. In this study, we examined the effects of IL-4 on the activation and
      collagen production of cultured human intrahepatic (myo)fibroblasts (hIHFs), and
      investigated the underlying mechanisms. The myofibroblastic nature of cells was
      evaluated morphologically using activation markers (smooth muscle alpha-actin,
      vimentin and prolyl 4-hydroxylase). Quiescent hIHFs were obtained by cell
      incubation in serum-free medium or cell culture on Matrigel. We first analyzed IL
      4 receptor expression, STAT-6 activation by IL-4, and STAT-6 inhibition by an
      anti-IL-4 antibody or by STAT-6 small-interfering RNA (siRNA) transfection. We
      then focused on collagen production, using quantitative real-time PCR to analyze
      the effect of IL-4 on the mRNA expression of collagens I, III and IV, and on
      collagen levels in supernatants of hIHFs, using the Sircol collagen assay. hIHFs
      cultured in plastic wells appeared to be morphologically activated. The
      expression of activation markers was reduced by serum deprivation or culture on
      Matrigel, and restored by IL-4 incubation. The IL-4 receptor was expressed by
      hIHFs, and STAT-6 was activated following incubation with IL-4. Both anti-IL-4
      antibody and STAT-6 siRNA transfection inhibited this activation. The treatment
      of hIHFs with IL-4 increased the mRNA expression of collagens I, III and IV
      (P<0.05) and elevated collagen levels in supernatants (P=0.01 vs untreated
      cells). Therefore, IL-4 exerts profibrotic effects by activating hIHFs and
      inducing collagen production and secretion. This effect requires IL4-R binding
      and STAT-6 activation. IL-4 may thus be involved in accelerated course of
      fibrogenesis during recurrent hepatitis C.

PMID- 18626469
TI  - Characterization of bacterial DNA binding to human neutrophil surface.
AB  - Bacterial DNA activates neutrophils through a CpG- and TLR9-independent
      mechanism. Neutrophil activation does not require DNA internalization, suggesting
      that it results from the interaction of bacterial DNA with a neutrophil surface
      receptor. The aim of this study was to characterize the interaction of bacterial
      DNA with the neutrophil surface. Bacterial DNA binding showed saturation and was
      inhibited by unlabeled DNA but not by other polyanions like yeast tRNA and poly
      A. Resembling the conditions under which bacterial DNA triggers neutrophil
      activation, binding was not modified in the presence or absence of calcium,
      magnesium or serum. Treatment of neutrophils with proteases not only dramatically
      reduced bacterial DNA binding but also inhibited neutrophil activation induced by
      bacterial DNA. Experiments performed with DNA samples of different lengths
      obtained after digestion of bacterial DNA with DNase showed that only DNA
      fragments greater than approximately 170-180 nucleotides competed bacterial DNA
      binding and retained the ability to trigger cell activation. Treatment of
      neutrophils with chemoattractants or conventional agonists significantly
      increased bacterial DNA binding. Moreover, neutrophils that underwent
      transmigration through human endothelial cell monolayers even in the absence of
      chemoattractants, exhibited higher binding levels of bacterial DNA. Together, our
      findings provide evidence that binding of bacterial DNA to neutrophils is a
      receptor-mediated process that conditions the ability of DNA to trigger cell
      activation. We speculate that neutrophil recognition of bacterial DNA might be
      modulated by the balance of agonists present at inflammatory foci. This effect
      might be relevant in bacterial infections with a biofilm etiology, in which
      extracellular DNA could function as a potent neutrophil agonist.

PMID- 18626470
TI  - Grand challenges for psychiatric drug discovery: a perspective.

PMID- 18626472
TI  - Single-strand break repair and genetic disease.
AB  - Hereditary defects in the repair of DNA damage are implicated in a variety of
      diseases, many of which are typified by neurological dysfunction and/or increased
      genetic instability and cancer. Of the different types of DNA damage that arise
      in cells, single-strand breaks (SSBs) are the most common, arising at a frequency
      of tens of thousands per cell per day from direct attack by intracellular
      metabolites and from spontaneous DNA decay. Here, the molecular mechanisms and
      organization of the DNA-repair pathways that remove SSBs are reviewed and the
      connection between defects in these pathways and hereditary neurodegenerative
      disease are discussed.

PMID- 18626473
TI  - DNA polymerases and human disease.
AB  - The human genome encodes at least 14 DNA-dependent DNA polymerases--a
      surprisingly large number. These include the more abundant, high-fidelity enzymes
      that replicate the bulk of genomic DNA, together with eight or more specialized
      DNA polymerases that have been discovered in the past decade. Although the roles
      of the newly recognized polymerases are still being defined, one of their crucial
      functions is to allow synthesis past DNA damage that blocks replication-fork
      progression. We explore the reasons that might justify the need for so many DNA
      polymerases, describe their function and mode of regulation, and finally consider
      links between mutations in DNA polymerases and human disease.

PMID- 18626477
TI  - A paradigm shift in the mechanisms of graft rejection.

PMID- 18626478
TI  - Meeting report of the conference on UV-Radiation-Induced Disease--Roles of UVA
      and UVB.

PMID- 18626479
TI  - Proteolytically active allergens cause barrier breakdown.
AB  - Two major allergens--the house dust mite Dermatophagoides pteronyssinus (Der p 1)
      and cockroach allergens--are proteolytically active and stimulate the protease
      activated receptor 2 (PAR-2). Jeong et al. (2008, this issue) exposed mouse and
      human epidermis to both allergens and correlated the observed delay in
      permeability barrier recovery to PAR-2 activation/signaling. This article exposes
      the secretive boundaries between barrier homeostasis and immunity.

PMID- 18626480
TI  - Langerhans cell dogma: another round of rejections.
AB  - Mice that are deficient in epidermal Langerhans cells allow the functions of
      these cells in vivo to be rigorously assessed. Experiments that have been carried
      out with these animals have yielded surprising results, leading to major changes
      in existing paradigms. In this issue, Obhrai and coworkers explore the
      involvement of Langerhans cells in skin graft rejection and describe fascinating
      results.

PMID- 18626481
TI  - Minor physical anomalies in autism: a meta-analysis.
AB  - Autism is a complex neurodevelopmental disorder in which the interactions of
      genetic, epigenetic and environmental influences play a causal role. Despite the
      compelling evidence for a strong heritability, the etiology and molecular
      mechanisms underlying autism remain unclear. High phenotypic variability and
      genetic heterogeneity confounds the identification of susceptibility genes. The
      lack of robust indicators to tackle this complexity in autism has led researchers
      to seek for novel diagnostic tools to create homogenous subgroups. Several
      studies have indicated that patients with autism have higher rates of minor
      physical anomalies (MPAs) and that MPAs may serve as a diagnostic tool; however,
      the results have been inconsistent. Using the cumulative data from seven studies
      on MPAs in autism, this meta-analysis seeks to examine whether the aggregate data
      provide evidence of a large mean effect size and statistical significance for
      MPAs in autism. It covers the studies using multiple research methods till June
      2007. The current results from seven studies suggested a significant association
      of MPAs in autism with a robust pooled effect size (d=0.84), and thereby provide
      the strongest evidence to date about the close association between MPAs and
      autism. Our results emphasize the importance of MPAs in the identification of
      heterogeneity in autism and suggest that the success of future autism genetics
      research will be exploited by the use of MPAs. Implications for the design of
      future studies on MPAs in autism are discussed and suggestions for further
      investigation of these important markers are proposed. Clarifying this relation
      might improve understanding of risk factors and molecular mechanisms in autism.

PMID- 18626482
TI  - Successful overweight prevention in adolescents by increasing physical activity:
      a 4-year randomized controlled intervention.
AB  - BACKGROUND: Population-based studies directed at promoting physical activity in
      youth have shown limited success in obesity prevention. OBJECTIVE: To assess
      whether an intervention integrating environmental changes to induce sustained
      changes in physical activity, prevents overweight in adolescents. DESIGN: Four
      year randomized trial started in 2002 in eight middle schools of Eastern France.
      The intervention, randomized at school level, was designed to promote physical
      activity by changing attitudes through debates and attractive activities, and by
      providing social support and environmental changes encouraging physical activity.
      SUBJECTS: Nine hundred and fifty four 12-year-old six-graders. MEASUREMENTS: Body
      mass index (BMI), body composition, physical activity by questionnaire, plasma
      lipids and glucose, insulin resistance. RESULTS: Intervention students had a
      lower increase in BMI (P=0.01) and age- and gender-adjusted BMI (P<0.02) over
      time than controls. The differences across groups of the age- and gender-adjusted
      BMI changes (95% confidence interval (CI)) were -0.29 (-0.51; -0.07) kg/m2 at 3
      years, -0.25 (-0.51; 0.01) kg/m2 at 4 years. An interaction with baseline weight
      status was noted. The intervention had a significant effect throughout the study
      in initially non-overweight adolescents (-0.36 (-0.60;-0.11) kg/m2 for adjusted
      BMI at 4 years), corresponding to a lower increase in fat mass index (P<0.001).
      In initially overweight adolescents, the differences observed across groups at 2
      years (-0.40 (-0.94; 0.13) kg/m2 for adjusted BMI) did not persist over time. At
      4 years, 4.2% of the initially non-overweight adolescents were overweight in the
      intervention schools, 9.8% in the controls (odds ratio=0.41 (0.22; 0.75);
      P<0.01). Independent of initial weight status, compared with controls,
      intervention adolescents had an increase in supervised physical activity
      (P<0.0001), a decrease of TV/video viewing (P<0.01) and an increase of high
      density cholesterol concentrations (P<0.0001). CONCLUSION: Enhancing physical
      activity with a multilevel program prevents excessive weight gain in non
      overweight adolescents. Our study provides evidence that prevention of obesity in
      youth is feasible.

PMID- 18626483
TI  - Body weight through adult life and risk of urinary incontinence in middle-aged
      women: results from a British prospective cohort.
AB  - OBJECTIVES: To determine whether the onset and duration of being overweight or
      obese are associated with symptoms of urinary incontinence. DESIGN: Nationally
      representative cohort study. SUBJECTS: A total of 1201 women followed-up since
      their birth in 1946 and annually from 48 to 54 years. MEASUREMENTS: The body mass
      index (BMI) at the age of 20, 26, 36 and 43, and symptoms of stress, urge and
      severe incontinence at seven consecutive years from age 48 to 54. RESULTS: In
      each year from age 48 to 54, almost half (46-49%) reported symptoms of stress
      incontinence, urge incontinence rose from 22 to 25% and severe incontinence from
      8 to 11%. At the age of 20, 26, 36 and 43, BMI was positively associated with
      stress symptoms and severe incontinence in midlife. BMI transition was found to
      have accumulation effects on symptoms of severe incontinence; women who were
      overweight/obese since age 20 years were more likely to report severe
      incontinence than women whose BMI remained below 25 kg/m(2) (odds ratio (95%
      confidence interval): 2.30 (1.36-3.93)) or who became overweight or obese at 43
      years (1.85 (0.97-3.51)). These relationships existed beyond the effects of
      aging, childhood enuresis, kidney infection, childbirth characteristics,
      menopause, educational attainment, general practitioner consultations and smoking
      status. BMI was not associated with symptoms of urge incontinence. CONCLUSIONS:
      Across adult life, higher BMI for women was linked with subsequent symptoms of
      stress and severe incontinence in midlife; those who were overweight or obese
      since early in adult life more than doubled their risk of severe incontinence.
      Women, and especially young women, should be encouraged to keep their weight in a
      normal range throughout adult life.

PMID- 18626484
TI  - Reversal of visceral adiposity in candy-diet fed female Wistar rats by the CB1
      receptor antagonist rimonabant.
AB  - OBJECTIVE: The severity of obesity is often more determined by the distribution
      of fat depots rather than by body weight itself. Therefore, the effect of
      rimonabant on fat distribution pattern was investigated in female candy-fed
      Wistar rats. DESIGN: Female Wistar rats were fed a high fat, high carbohydrate
      (candy-) diet for 12 weeks. During the last 6 weeks rats were treated with
      rimonabant. Food intake and body weight development were investigated, as well as
      effects on total body fat, especially visceral fat and ectopic lipid accumulation
      in skeletal muscle and liver, determined by in vivo magnetic resonance
      imaging/magnetic resonance spectroscopy. RESULTS: Candy-diet increased body
      weight, which was predominantly due to the increased total fat mass with
      predominance of visceral fat accumulation. Treatment with rimonabant fully
      reversed the weight gain and fat deposition in the visceral cavity and skeletal
      muscle, in contrast to pair feeding. In spite of an only transient reduction of
      food intake, body weight reduction, as well as normalized body fat, reduced
      visceral fat and intramyocellular lipids were maintained over the treatment
      period. CONCLUSIONS: We conclude that additional factors other than reduced
      caloric intake must be responsible for the improvements in these lipid
      parameters. The complete cluster of results is consistent with increased lipid
      oxidation caused by rimonabant.

PMID- 18626485
TI  - Childhood overweight and obesity prevalences levelling off in Stockholm but
      socioeconomic differences persist.
AB  - BACKGROUND: Time trends in overweight, obesity and underweight among 10-year-old
      children were investigated between 1999 and 2003 with attention to gender and
      areas with different socioeconomic status (SES). MATERIAL: The study was
      performed in Stockholm County, where schools within eight different SES areas
      were randomly sampled. In selected schools, data on height and weight were
      abstracted from school health records of 2416 ten-year-old boys and girls
      examined by school nurses in 1999 and 2183 examined in 2003. RESULTS: Among boys,
      the prevalence of overweight was 21.6% in 1999 and 20.5% in 2003 (difference 
      1.1% (95% confidence interval (CI), -4.6; 2.4)) and for obesity 3.2 and 3.8%
      (difference 0.6% (95% CI, -0.9; 2.2)). Among girls overweight decreased from 22.1
      to 19.2% (difference -2.9% (95% CI, -6.3; 0.6)) and obesity from 4.4 to 2.8%
      (difference -1.6% (95% CI, -3.1; 0.0)). There was a marginally significant
      difference in obesity trends in girls versus boys (P=0.051). The prevalence of
      underweight decreased nonsignificantly both in boys and in girls. Strong
      gradients, with more obesity and overweight in socioeconomically disadvantaged
      areas, were observed in both genders in 2003. Differences between SES areas were
      also seen in 1999 but were more pronounced in 2003. Among boys divergent trends
      in obesity were observed between 1999 and 2003, with evidence for increases in
      less affluent areas only. CONCLUSION: This population-based study of 10-year-olds
      indicates that rates of obesity, overweight and underweight are stable in
      Stockholm County. However, obesity is more prevalent in relatively less
      advantaged SES.

PMID- 18626486
TI  - Methyl donor supplementation prevents transgenerational amplification of obesity.
AB  - BACKGROUND: The obesity epidemic, recognized in developed nations for decades, is
      now a worldwide phenomenon. All age groups are affected, including women of
      childbearing age, fueling concern that maternal obesity before and during
      pregnancy and lactation impairs developmental establishment of body weight
      regulatory mechanisms in the fetus or infant, causing transgenerational
      amplification of obesity prevalence and severity. The biological mechanisms
      underlying such processes remain unknown. METHODS: We used agouti viable yellow
      (A(vy)) mice to test the hypothesis that maternal obesity induces
      transgenerational amplification of obesity. We passed the A(vy) allele through
      three generations of A(vy)/a females and assessed cumulative effects on coat
      color and body weight. By studying two separate but contemporaneous populations
      of mice, one provided a standard diet and the other a methyl-supplemented diet
      that induces DNA hypermethylation during development, we tested whether potential
      transgenerational effects on body weight might be mediated by alterations in
      epigenetic mechanisms including DNA methylation. RESULTS: The genetic tendency
      for obesity in A(vy) mice was progressively exacerbated when the A(vy) allele was
      passed through successive generations of obese A(vy) females. This
      transgenerational amplification of body weight was prevented by a promethylation
      dietary supplement. Importantly, the effect of methyl supplementation on body
      weight was independent of epigenetic changes at the A(vy) locus, indicating this
      model may have direct relevance to human transgenerational obesity. CONCLUSION:
      Our results show that in a population with a genetic tendency for obesity,
      effects of maternal obesity accumulate over successive generations to shift the
      population distribution toward increased adult body weight, and suggest that
      epigenetic mechanisms are involved in this process.

PMID- 18626487
TI  - Topical anesthesia blunts the pressor response induced by bowel manipulation in
      subjects with cervical spinal cord injury.
AB  - DESIGN: Prospective double-blind study. OBJECTIVE: Manual emptying of rectal
      contents is necessary for patients with spinal cord injury to prevent bowel
      obstruction; however, this maneuver induces a rise in blood pressure (BP) and
      autonomic dysreflexia (AD). The purpose of this prospective double-blind study
      was to investigate whether topical anorectal anesthesia attenuates the BP rise
      and AD during bowel manipulation in patients with cervical spinal cord injury
      (CSCI). SETTING: Kibikogen Rehabilitation Center for Employment Injuries.
      METHODS: The study subjects were 25 consecutive clinically stable patients with
      CSCI. Each subject received a complete bowel program involving manual removal of
      stool in lateral recumbency, after topical application of lidocaine or placebo
      jelly to the anorectal area. Systolic and diastolic BP, heart rate and symptoms
      of AD were recorded before, during and after bowel manipulation. RESULTS:
      Systolic BP was significantly lower during the lidocaine arm of the study
      compared with placebo at insertion of rectal medication, digital stimulation,
      beginning of stool flow, manual removal of stool, end of stool flow and at 5-min
      after emptying. The mean maximal increase in systolic BP during lidocaine
      treatment (33.2+/-14.6 mm Hg) was less than during placebo (50.2+/-19.5 mm Hg,
      P<0.001). CONCLUSION: On the basis of our findings, we recommend induction of
      lidocaine jelly immediately before rectal manipulation in patients with CSCI to
      minimize the incidence and severity of AD.

PMID- 18626488
TI  - Biological implications of glycosaminoglycan interactions with haemopoietic
      cytokines.
AB  - Heparan sulphate (HS) glycosaminoglycans (GAGs) are an integral part of the
      signalling complex of fibroblast derived growth factor (FGF) family members, HS
      being regarded as a coreceptor. FGFs are also retained in the tissues by binding
      to HS structures. Early studies on the contribution of the bone marrow stroma to
      haemopoiesis suggested that cytokines with a role in haemopoiesis were similarly
      retained in the stroma through interactions with HS. However, the functional
      outcomes of these cytokines binding HS were poorly understood. Here the GAG
      binding properties of cytokines of the four alpha-helical bundle family and the
      biological consequences of such binding are reviewed. From this analysis it is
      apparent that although many of these cytokines do bind GAGs, GAG binding is not a
      consistent feature, nor is the site of GAG binding conserved among these
      cytokines. The biological outcome of GAG binding depends, in part, on the
      location of the GAG-binding site on the cytokine. In some cases GAG binding
      appears to block signalling, whereas in others signalling is likely to be
      facilitated by binding. It is postulated that the interactions of these cytokines
      with their receptor complexes evolved independently of GAG binding, with GAG
      binding being an additional feature for a subset of this cytokine family.
      Nevertheless, because GAG binding localizes cytokines to sites within tissues,
      these interactions are likely to be critically important for the biology of these
      cytokines.

PMID- 18626489
TI  - Impact of glycans on T-cell tolerance to glycosylated self-antigens.
AB  - There is now substantial evidence that antigen post-translational modifications
      are recognized by T cells, and alterations in epitope modification has been
      linked to a number of autoimmune diseases. An estimated one third of the MHC
      ligands contain post-translational modification of epitopes. A common post
      translational modification of proteins is glycosylation and it is predicted on
      theoretical grounds that approximately 1-5% of MHC ligands may bear a glycan.
      From numerous studies over the past 15 years it is clear that glycans can
      influence T cell responses either by contribution to the structure of the epitope
      or by influencing the profile of peptide epitopes presented by APCs. The
      influence of glycans on antigen processing and T cell recognition has particular
      relevance to the induction of tolerance to self-antigens. Here we discuss the
      potential impact of glycans on the profile of self-epitopes presented by APCs and
      the consequence of changes in glycosylation to generate neo self-epitopes
      resulting in the loss of tolerance and the development of autoimmune diseases.
      With the recent developments in profiling T cell epitopes, and with strategies
      for modulating glycosylation in vivo, it is now feasible to directly examine the
      global influence of glycans on self-tolerance and autoimmunity.

PMID- 18626492
TI  - Challenges of targeting vascular stability in acute kidney injury.
AB  - Acute kidney injury following folate administration is characterized by a
      vascular remodeling that is initially proliferative but subsequently results in
      vascular endothelial loss. Interventions directed toward promoting endothelial
      growth may preserve vascular structure and therefore renal function. However,
      angiopoietin-1 therapy in the setting of folate-induced acute kidney injury
      resulted in an expanded fibrotic response despite apparent preservation of the
      vasculature, indicating that renal repair responses are complex and vascular
      directed therapies should be approached with caution.

PMID- 18626493
TI  - Glomerular filtration: the charge debate charges ahead.
AB  - The concept that the glomerular filtration barrier exhibits charge selectivity is
      a basic tenet of renal physiology. Heparan sulfate is a major contributor of
      glomerular anionic charge. In a new study, prevention of podocytes from
      synthesizing heparan sulfate, via mutation of Ext1, causes only mild,
      statistically insignificant albuminuria, despite dramatic alterations in
      glomerular anionic charge.

PMID- 18626494
TI  - When less is more: apoptosis during acute kidney injury.
AB  - The paper by Ma and Devarajan suggests that the subtle apoptotic events that
      occur in the distal nephron after acute kidney injury might have a greater than
      expected impact on the adjacent proximal tubules and kidney function.
      Understanding these events might facilitate development of therapeutic means to
      ameliorate acute kidney injury.

PMID- 18626495
TI  - Prescribing and monitoring hemodialysis dose.
AB  - Small patients require higher Kt/V, the ratio of dialysis dose (the product of
      small-molecule clearance (K) and dialysis session length (t) to body water volume
      (V), than large patients. The errors implicit in Kt/V for judging hemodialysis
      dose are reviewed; methods for prescribing hemodialysis based on new technology
      are discussed; and thoughts about future development are suggested.

PMID- 18626497
TI  - Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients
      with chronic kidney disease: results of the study to evaluate early kidney
      disease.

PMID- 18626498
TI  - Vitamin D levels and early mortality among incident hemodialysis patients.

PMID- 18626500
TI  - Renal microvascular and tubular injuries in type II diabetic nephropathy.

PMID- 18626501
TI  - Rituximab in membranous nephropathy.

PMID- 18626505
TI  - The case. Do not forget nails.

PMID- 18626506
TI  - Erythrophagocytosis by renal tubular cells.

PMID- 18626507
TI  - Impact of nerve sparing on surgical margins and biochemical recurrence: results
      from the SEARCH database.
AB  - The effects of nerve sparing on the risk of positive surgical margins (PSMs) and
      biochemical recurrence after radical prostatectomy (RP) remain controversial. We
      examined data from 1018 men treated by RP between 1988 and 2006 at five centers
      in the Shared Equal Access Regional Cancer Hospital database. Neither bilateral
      nor unilateral nerve-sparing techniques were associated with a higher risk of
      PSM; on multivariate analysis of individual sides, the risk of PSM on either side
      was not increased by nerve sparing on either side. The risk for biochemical
      recurrence was not affected by bilateral or unilateral nerve sparing. When used
      on appropriately selected patients, nerve sparing does not increase the
      probability of PSM or biochemical recurrence after RP.

PMID- 18626508
TI  - Specific targeting of prostate cancer cells in vitro by the suicide gene/prodrug
      system, uracil phosphoribosyltransferase/5-fluorouracil, under the control of
      prostate-specific membrane antigen promoter/enhancer.
AB  - This study was designed to investigate the prostate cancer-specific tumoricidal
      effect of the suicide gene, Escherichia coli uracil phosphoribosyltransferase
      (UPRT), driven by the human prostate-specific membrane antigen promoter/enhancer
      (PSMA(E/P)) in vitro. When transfected with PSMA(E/P)-EGFP (enhanced green
      fluorescence protein) (a plasmid construct with the green fluorescence protein
      gene driven by the PSMA(E/P)), only the androgen-responsive and PSMA-positive
      prostate cancer cell line, LNCaP, expressed GFP, indicating the specificity of
      the PSMA(E/P) activity in androgen-sensitive and PSMA-positive prostate cancer
      cells. Taking advantage of this prostate cancer-specific property of PSMA(E/P),
      we successfully introduced bacterial UPRT into LNCaP cells where the tumoricidal
      effect of 5-fluorouracil (5-FU) was significantly increased when compared with
      the cells without the exogenous UPRT. We conclude that the efficacy of 5-FU-based
      chemotherapy in prostate cancers can be significantly improved by targeted
      expression of the suicide gene UPRT under the control of PSMA(E/P).

PMID- 18626509
TI  - Diagnostic accuracy of extended biopsies for the staging of microfocal prostate
      cancers in autopsy specimen.
AB  - Clinically insignificant prostate cancers may be predicted when biopsies show a
      microfocal cancer (MiFC). However, at least one-third of MiFC are underestimated
      by biopsies. The aim of this study was to evaluate the staging accuracy of
      different biopsy regimen showing a MiFC. We performed 18 biopsy cores on 164
      autopsy prostates. Six cores were taken from the mid-peripheral zone (MPZ), 6
      from the lateral PZ (LPZ) and 6 from the central zone (CZ). We tested seven
      different biopsy regimens by distinguishing the MPZ, LPZ or CZ biopsies either
      separately or associated with each other. Of the cancers detected by biopsies, we
      selected those showing a MiFC and compared our findings with whole mount
      analysis. The positive predictive value of a MiFC referred to how often, when
      needle biopsies showed a MiFC, there was a clinically insignificant cancer on
      whole mount prostate analysis. We found that the positive predictive value of a
      MiFC on 6 or 12 biopsy cores was similar irrespective of biopsy location (P
      approximately 1). On MPZ, MPZ plus LPZ and all 18 biopsies, it was 40, 70 and
      87%, respectively (P<0.1). Tumor volume of cancers showing a MiFC on MPZ biopsies
      was significantly higher than those showing a MiFC on MPZ plus LPZ, or all 18
      biopsies (P<0.05). These results show that performing additional cores in case of
      MiFC on sextant biopsies may help differentiating significant from insignificant
      cancers.

PMID- 18626510
TI  - PTEN: a default gate-keeping tumor suppressor with a versatile tail.
AB  - The tumor suppressor PTEN controls a variety of biological processes including
      cell proliferation, growth, migration, and death. As a master cellular regulator,
      PTEN itself is also subjected to deliberated regulation to ensure its proper
      function. Defects in PTEN regulation have a profound impact on carcinogenesis. In
      this review, we briefly discuss recent advances concerning PTEN regulation and
      how such knowledge facilitates our understanding and further exploration of PTEN
      biology. The carboxyl-tail of PTEN, which appears to be associated with multiple
      types of posttranslational regulation, will be under detailed scrutiny. Further,
      a comparative analysis of PTEN and p53 suggests while p53 needs to be activated
      to suppress tumorigenesis (a dormant gatekeeper), PTEN is probably a constitutive
      surveillant against cancer development, thus a default gatekeeper.

PMID- 18626511
TI  - Differential effects of p63 mutants on transactivation of p53 and/or p63
      responsive genes.
AB  - p63, known to play a role in development, has more recently also been implicated
      in cancer progression. Mutations in p63 have been shown to be responsible for
      several human developmental diseases. Differential splicing of the p63 gene gives
      rise to p63 isoforms, which can act either as tumor suppressors or as oncogene.
      In this report, we studied the effects of naturally occurring TAp63gamma mutants
      on the regulation of p53/p63 and p63 specific target genes. We observed
      significant differences among p63 mutants to regulate the p53/p63 and p63
      specific target genes. Additionally, we observed a differential effect of p63
      mutants on wildtype-p63-mediated induction of p53/p63 and p63 specific target
      genes. We also demonstrated that these mutants differentially regulate the
      binding of wildtype p63 to the promoter of target genes. Furthermore, the effects
      of these mutants on cell death and survival were consistent with their ability to
      regulate the downstream targets when compared to wildtype TAp63gamma. In summary,
      our data demonstrate that p63 mutants exhibit differential effects on p63 and
      p53/p63 specific target genes and on the induction of apoptosis, and provide
      further insight into the function of p63.

PMID- 18626512
TI  - A case of systemic polyarteritis nodosa with spermatic cord involvement.
AB  - BACKGROUND: A 50-year-old man with a history of hyperlipidemia and hypertension
      presented to an emergency department after 10 days of fevers (temperature 40
      degrees C), headache, malaise, myalgia, poor appetite, diarrhea, and weight loss
      of 6.35 kg. He would subsequently develop bilateral scrotal swelling and pain
      during his evaluation. INVESTIGATIONS: Physical examination, CBC, blood chemistry
      panel, measurement of erythrocyte sedimentation rate and C-reactive protein
      level, liver function profile, urinalysis, lumbar puncture, blood cultures, urine
      cultures, cerebrospinal fluid culture, stool analysis and cultures, multiple
      viral studies including hepatitis serologies, measurement of antineutrophil
      cytoplasmic autoantibody levels, urine protein electrophoresis, serum protein
      electrophoresis, CT of the head, chest, abdomen and pelvis, MRI of the brain,
      temporal artery biopsy and pathologic analysis, scrotal ultrasonography, right
      spermatic cord biopsy and pathologic analysis. DIAGNOSIS: Polyarteritis nodosa
      with involvement of both spermatic cords. MANAGEMENT: Prednisone 60 mg daily was
      started for presumed temporal arteritis, but was discontinued when no evidence of
      arteritis was found in the temporal artery biopsy specimen. When pathologic
      analysis of the spermatic cord biopsy tissue confirmed polyarteritis nodosa,
      prednisone 40 mg twice daily was administered and the patient's scrotal pain and
      swelling resolved quickly. Steroids were slowly tapered and discontinued over the
      next 18 months. He remained free of systemic symptoms, with normal results on
      physical examination and laboratory evaluation, including urinalysis, CBC,
      erythrocyte sedimentation rate and C-reactive protein level, 5.5 months after
      discontinuation of glucocorticoid therapy.

PMID- 18626513
TI  - Neoadjuvant chemotherapy for the treatment of muscle-invasive bladder cancer:
      argument in favor.

PMID- 18626514
TI  - Development and Characterization of Degradable Thiol-Allyl Ether Photopolymers.
AB  - Degradable thiol-ene photopolymer networks were formed through radically mediated
      step growth reactions. Variations in the network structure were used to alter the
      initial and temporal moduli, mass loss profiles, and equilibrium swelling ratios.
      Mass loss rates varied with changes in the solvent concentration, monomer
      molecular weight, average monomer functionality, and concentration of degradable
      linkages. The time required for the networks to degrade completely ranged from
      1.20 +/- 0.01 to 24.5 +/- 0.1 days, which corresponded to hydrolysis rates of
      0.18 +/- 0.01 and 0.021 +/- 0.0003 days(-1). Initial moduli also varied
      considerably as a function of network structure, ranging from 150 +/- 35 to
      nearly 5000 +/- 100 kPa, and initial equilibrium swelling ratios ranged from 2.5
      +/- 0.01 to 18.7 +/- 2. Collectively, these results demonstrate how the material
      properties and the mass loss behavior of thiol-ene networks can be independently
      tuned for specific applications.

PMID- 18626515
TI  - Happy and fearful emotion in cues and targets modulate event-related potential
      indices of gaze-directed attentional orienting.
AB  - The goal of the present study was to characterize the effects of valence in
      facial cues and object targets on event-related potential (ERPs) indices of gaze
      directed orienting. Participants were shown faces at fixation that concurrently
      displayed dynamic gaze shifts and expression changes from neutral to fearful or
      happy emotions. Emotionally-salient target objects subsequently appeared in the
      periphery and were spatially congruent or incongruent with the gaze direction.
      ERPs were time-locked to target presentation. Three sequential ERP components
      were modulated by happy emotion, indicating a progression from an expression
      effect to a gaze-by-expression interaction to a target emotion effect. These
      effects included larger P1 amplitude over contralateral occipital sites for
      targets following happy faces, larger centrally distributed N1 amplitude for
      targets following happy faces with leftward gaze, and faster P3 latency for
      positive targets. In addition, parietally distributed P3 amplitude was reduced
      for validly cued targets following fearful expressions. Results are consistent
      with accounts of attentional broadening and motivational approach by happy
      emotion, and facilitation of spatially directed attention in the presence of
      fearful cues. The findings have implications for understanding how socioemotional
      signals in faces interact with each other and with emotional features of objects
      in the environment to alter attentional processes.

PMID- 18626517
TI  - Acute pulmonary embolism risk stratification.

PMID- 18626516
TI  - In-cell biochemistry using NMR spectroscopy.
AB  - Biochemistry and structural biology are undergoing a dramatic revolution. Until
      now, mostly in vitro techniques have been used to study subtle and complex
      biological processes under conditions usually remote from those existing in the
      cell. We developed a novel in-cell methodology to post-translationally modify
      interactor proteins and identify the amino acids that comprise the interaction
      surface of a target protein when bound to the post-translationally modified
      interactors. Modifying the interactor proteins causes structural changes that
      manifest themselves on the interacting surface of the target protein and these
      changes are monitored using in-cell NMR. We show how Ubiquitin interacts with
      phosphorylated and non-phosphorylated components of the receptor tyrosine kinase
      (RTK) endocytic sorting machinery: STAM2 (Signal-transducing adaptor molecule),
      Hrs (Hepatocyte growth factor regulated substrate) and the STAM2-Hrs heterodimer.
      Ubiquitin binding mediates the processivity of a large network of interactions
      required for proper functioning of the RTK sorting machinery. The results are
      consistent with a weakening of the network of interactions when the interactor
      proteins are phosphorylated. The methodology can be applied to any stable target
      molecule and may be extended to include other post-translational modifications
      such as ubiquitination or sumoylation, thus providing a long-awaited leap to high
      resolution in cell biochemistry.

PMID- 18626518
TI  - Correlation of clinical phenotype with a pericentric inversion of chromosome 9
      and genetic counseling.
AB  - OBJECTIVE: To describe the history of 157 carriers of pericentric inversions on
      chromosome 9 [inv9] with karyotype analyses and evaluate the significance of
      these findings. METHODS: We studied the incidence, clinical significance, and
      genetic counseling of inv9 p11;q12, p11;q13, and p11;q21 patients who were
      referred to our laboratory from various clinics of the Medical Faculty, Cukurova
      University, Adana, Turkey retrospectively from 157 cases of 15528 cytogenetic
      analyses collected between May 1993 and February 2007. RESULTS: We found the
      incidence of inv9 to be 1.01%. From a review of 157 cases with inv9, it is
      concluded that the incidence of the spontaneous abortion group 30.6% appeared to
      be high among the adult patients with inv9. The 17 cases were found to have
      mental retardation, which gave an incidence of 10.8%. We here report the clinical
      and cytogenetic findings of 157 inv9 cases that had different problems.
      CONCLUSION: Although, inv9 has been considered to be a normal variant, our
      observation implies a possible association between inv9 and abnormalities,
      suggesting that a susceptibility locus for these phenotypes may be located at the
      breakpoint of the inversion on chromosome 9, which may lead to cloning of a
      susceptibility gene for unspecified abnormalities. These findings could be used
      widely in clinical genetics, and as an effective tool for genetic counseling and
      reproductive guidance.

PMID- 18626519
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy in Arabs.
AB  - OBJECTIVE: To investigate the Notch 3 mutation spectrum in Arab patients with
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy CADASIL, which is an inherited cerebrovascular disease
      characterized by recurrent subcortical ischemic stroke starting in the third or
      fourth decade. METHODS: Complete neurological evaluation and sequencing of the
      Notch 3 gene were carried out at King Faisal Specialist Hospital & Research
      Centre in 2007 on 2 families from Riyadh, Kingdom of Saudi Arabia and Sudan
      affected by CADASIL. RESULTS: The index cases had adult onset stroke, vascular
      dementia, behavioral and psychiatric symptoms and accelerated deaths. In both
      families, abnormal magnetic resonance imaging findings were detected in
      symptomatic and asymptomatic individuals. All Notch 3 exons were screened for
      mutations in both families and no known or novel mutation could be found;
      although, in one family the brain biopsy showed the typical granular osmiophilic
      material deposition and the vascular smooth muscle cells. CONCLUSION: This is the
      first 2 cases of CADASIL in Arabs, which occur without an obvious Notch 3
      mutation.

PMID- 18626520
TI  - The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the
      diagnosis of primary and secondary lung carcinomas.
AB  - OBJECTIVE: To study the value of immunohistochemical staining of thyroid
      transcription factor-1 TTF-1, cytokeratin 7 CK7, and cytokeratin 20 CK20 in the
      differentiation between primary and secondary pulmonary carcinomas. METHODS:
      Forty-three cases of lung carcinoma, 14 squamous cell carcinoma, 12
      adenocarcinoma, 8 small cell carcinoma, 3 mesothelioma, and 6 metastatic tumors,
      were collected from the files of the Pathology Department, King Abdul-Aziz
      University Hospital, Jeddah, Saudi Arabia between 2004 and 2006. All cases were
      stained immunohistochemically following Avidin biotin method using monoclonal
      antibodies to TTF-1, CK7, and CK20. RESULTS: Immunohistochemical staining of 43
      cases of lung carcinoma revealed nuclear immunoreactivity for TTF-1 in all
      primary adenocarcinoma, and small cell carcinoma, while cases of squamous cell
      carcinoma were negative. Mesotheliomas were negative to TTF-1, CK7, and CK20.
      Metastatic tumors except for one case metastatic from the thyroid gland were
      negative to TTF-1. Cytokeratin 7 was positively expressed in primary tumors of
      lung, as well as metastatic tumors from the thyroid and breast. Cytokeratin 20
      was negative in all primary lung tumors, while positive in metastatic carcinomas
      from the colon. CONCLUSION: Thyroid transcription factor-1 is a sensitive marker
      for diagnosis of primary pulmonary adenocarcinoma, and differentiation between
      poorly differentiated squamous cell carcinoma and small cell carcinoma and
      adenocarcinoma. Cytokeratin 20 could be a marker for metastatic tumors from the
      colon to the lung since it was negative in all primary lung tumors.

PMID- 18626521
TI  - Histopathological patterns of nasopharyngeal carcinoma in Sudan.
AB  - OBJECTIVE: To study the histological patterns of nasopharyngeal carcinoma NPC in
      Sudanese patients and to compare them with the internationally published series.
      METHODS: A retrospective review for records of NPC patients treated in the
      Institute of Nuclear Medicine, Molecular Biology and Oncology INMO, Wadmedani,
      Sudan, during the period 2000-2005 was conducted. Parameters included in the
      review were histological types of NPC according to the World Health Organization
      WHO classification, age, gender, locality, ethnicity, and stage. All cases of NPC
      with positive histology were included while other types of histology lymphoma,
      sarcoma were excluded. The SPSS software was used for data entry and analysis.
      RESULTS: Total number of patients with NPC was 103. Age range from 11-82 years,
      median was 41 years, and mean was 45.5 years of age. Male:female ratio was 2:1.
      The WHO histology type-3 was 73.8% of cases, WHO type-2 was 26.2%, and there was
      no case of WHO type-1 found in this study population. Neck swelling is the most
      common presenting symptom 77.8%. CONCLUSION: Pattern of NPC classification
      resembles those seen in endemic areas like South China. Dominant histology was
      WHO type-3. Identifying risk factors for NPC in Sudan is required.

PMID- 18626522
TI  - The effect of etoricoxib premedication on postoperative analgesia requirement in
      orthopedic and trauma patients.
AB  - OBJECTIVE: We hypothesized that etoricoxib premedication would reduce the need
      for additional opioids following orthopedic trauma surgery. METHODS: A double
      blind, controlled study, conducted in King Fahd University Hospital, King Faisal
      University, Dammam, Kingdom of Saudi Arabia. After obtaining the approval of the
      Research and Ethics Committee and written consent, 200 American Society of
      Anesthesiology grade I & II patients that underwent elective upper limb or lower
      limb fracture fixation surgeries during the period from August 2005 to October
      2007 were studied. Patients were randomly premedicated using 120 mg of etoricoxib
      or placebo n=100, each. To alleviate postoperative pain, a patient controlled
      analgesia device was programmed to deliver one mg of morphine intravenously
      lockout time, 6 minutes. Visual analog scale and total postoperative morphine
      consumption over 24 hours and the adverse effects were recorded. RESULTS: One
      hundred patients in each group completed the study period. Etoricoxib
      premedication provides a statistically significant postoperative morphine sparing
      effect over 24 hours postoperatively. Total morphine consumption was 44.2 (8.2)
      in the placebo and 35.17.0mg in the etoricoxib groups p<0.001. The incidence of
      nausea and vomiting requiring treatment was lower in the etoricoxib group,
      p=0.014. The postoperative blood loss was similar in both groups. CONCLUSION:
      Etoricoxib is a suitable premedication before traumatic orthopedic surgery as it
      enhanced postoperative analgesia and reduced the need for morphine.

PMID- 18626523
TI  - Duration of venous occlusion with lidocaine for preventing propofol induced pain.
AB  - OBJECTIVE: To study the effect of the venous occlusion duration using lidocaine
      on the incidence and severity of propofol induced pain. METHODS: A prospective
      double-blind randomized study was designed at Jordan University Hospital, Amman,
      Jordan between October 2007 and November 2007. One hundred and fifty patients
      aged 14-70 years, American Society of Anesthesiologists (ASA) clinical status I
      and II who underwent elective surgeries under general anesthesia, were divided
      into 3 groups. All 3 groups had propofol 1% infusion at a constant rate after
      applying venous occlusion with lidocaine. The occlusion was applied for 15
      seconds (group I, n=50), 30 seconds (group II, n=50) and 60 seconds (group III,
      n=50). Pain was assessed during injection according to a verbal pain score.
      RESULTS: Fourteen patients 28% had pain in group I, compared to 16 patients 32%
      in group II, and 9 patients 18% in group III. This difference did not reach
      statistical significance p>0.05 for the incidence and severity of pain.
      CONCLUSION: While venous occlusion with lidocaine is an effective method in
      relieving propofol induced pain, we found no difference when the duration of
      venous occlusion was 15, 30, or 60 seconds.

PMID- 18626524
TI  - Intravenous immunoglobulin utilization in a tertiary care teaching hospital in
      Saudi Arabia.
AB  - OBJECTIVE: To evaluate the effect of intravenous immunoglobulin IVIG utilization
      at King Khalid University Hospital, an 850 bed tertiary care academic center,
      over a-3-year period. METHODS: Patients who received IVIG in the period from
      January 2003 to December 2005 at King Khalid University Hospital were identified
      retrospectively using the hospital computer system. Their charts were
      subsequently reviewed. We collected data pertaining to patients' demographics,
      indication of IVIG, dose regimen and physician specialty. Indications were
      categorized into 4 different categories: US Food and Drug Administration FDA
      labeled; off-label recommended as first line; off-label recommended as
      alternative; and not recommended. RESULTS: A total of 305 patients were
      identified. Intravenous immunoglobulin was given to 109 (35.7%) patients for FDA
      labeled indications, 29 (9.5%) patients for off-label recommended as first line
      indications, 97 (31.8%) for off-label recommended as alternative indications, and
      70 (23%) for not recommended indications. The amount of IVIG consumed during the
      study period was 43.65 Kgs with an estimated cost of $1.75 million, 24.4% of
      which was considered inappropriate use. Hematologists and neurologists were the
      most frequent prescribers. CONCLUSION: A significant amount of IVIG was
      prescribed for inappropriate indications. This had a large financial burden on an
      already strained hospital budget.

PMID- 18626525
TI  - Influence of androgens on bone mass in young women with sickle cell anemia.
AB  - OBJECTIVE: To evaluate the relationship between the gender hormonal levels and
      bone mineral density in premenopausal women suffering with sickle cell disease.
      METHODS: A cross-sectional study including consecutive female adult patients with
      sickle cell anemia attending the outpatient hematology/orthopaedic clinics, or
      admitted to King Fahd University Hospital, Al-Khobar, Saudi Arabia, between
      August 2006 and June 2007. Patient's age was documented, and body mass index was
      calculated. Blood was drawn for complete blood picture, biochemistry, and
      hormonal profile including total estradiol E2 and total testosterone Te. Bone
      mineral density BMD was measured for all patients using dual energy x-ray
      absorptiometry scan at the hip and lumbar spine. RESULTS: We analyzed the data of
      51 patients with an average age of 26+/-3.1 years. Patients were divided into 2
      groups group A and group B. Group A had normal BMD and group B with low BMD.
      Thirty-one (60.8%) were in group A and 20 (39.2%) were in group B. The E2 level
      was not statistically different between the 2 groups, while Te level was
      significantly lower in women with low BMD 38+/-11.8 versus 22.3+/-11.7 ng/dl,
      p<0.001. CONCLUSION: Our study indicates that in premenopausal female patients
      with sickle cell anemia, testosterone may play a role in the preservation of bone
      mass.

PMID- 18626526
TI  - Magnitude and determinants of osteoporosis in adult population of South Sharqiya
      region of Oman.
AB  - OBJECTIVE: To estimate the incidence of hip fractures as an indicator for
      osteoporosis in the >40 years old Omani population of the South Sharqiya region
      of Oman. We also recommended a policy for addressing osteoporosis in this
      community. METHODS: Orthopedic surgeons noted and treated patients with hip
      fracture that were due to a fall over 5 years September 2002 to August 2007 at
      Sur Hospital, Oman. Their preoperative information, such as bone involved, co
      morbidities, history of fractures, and the type of treatment were collected. We
      used the population of the study area to calculate the annual incidence of
      fractures. RESULTS: In our study, 147 persons 70 male, and 77 female of >40 years
      with hip fractures were included. The age adjusted annual incidence rate of hip
      fracture in >40 population of South Sharqiya was 0.14%. While operating on 96
      65.3% patients, we used dynamic hip screw. Hemi-arthroplasty with Austin-Moore
      prosthesis was performed in 37 (24.5%) patients. Eighteen (12.2%) patients had
      previous bone fractures. CONCLUSION: The incidence of hip fracture was high.
      Osteoporosis screening programs and adequate interventions could detect the high
      risk group and prevent such fractures in the future.

PMID- 18626527
TI  - The effects of combined use of glutamine and growth hormone on the bacterial
      translocation associated with obstructive jaundice.
AB  - OBJECTIVE: To investigate the effects of combined use of glutamine and growth
      hormone on bacterial translocation. METHODS: The study was performed at the
      laboratories of the Department of Physiology at Ataturk University Medical
      School, Erzurum, Turkey between June and September 2007. Forty rats divided into
      5 groups of 8, were included in the study. In the study groups, the common bile
      duct was ligated to obtain obstructive jaundice. The rats in the control group CG
      were given sodium chloride, in the glutamine group GLG they were given glutamine,
      in the growth hormone group GHG, growth hormone, and in the glutamine + growth
      hormone group GLGHG glutamine + growth hormone at equal doses by the same
      methods. Blood, spleen, liver, lymph node, and cecal content samples were
      obtained. Total bilirubin TB, alkaline phosphates ALP, and gamma glutamine
      transferase GGT activities were evaluated. RESULTS: In the CG, cecal contents
      were higher than in the GLG, and cecal contents and BT were higher than in the
      GHG and the GLGHG. The BT rate was the lowest in the GLGHG, with a borderline
      difference with the values of the GLG and GHG. CONCLUSION: We found that in
      preventing BT, combined use of glutamine, and growth hormone was more effective
      than using each of these agents alone.

PMID- 18626528
TI  - Nasal packing in cosmetic and functional nasal surgery.
AB  - OBJECTIVE: To evaluate the routine use of nasal packing after cosmetic and
      functional nasal surgery. METHODS: Prospective collection from 2005 to 2006 at
      King Abdulaziz University Hospital in Riyadh for 54 patients post
      septorhinoplasty with and without submucous diathermy or lateralization of
      inferior turbinate were evaluated for efficacy and complications of nasal packing
      which kept for different duration. RESULTS: All 54 patients had septoplasty, 21
      with rhinoplasty, 12 with SMD, and 24 patients had inferior turbinate
      lateralization. Eight cm slim Merocel packed in 67 nasal cavity sides, 8 cm
      regular Merocel packed in 24 sides and 10 cm regular Merocel packed in 6 sides.
      Thirty-seven patients had the pack for 6 hours then removed and 17 patients had
      it for 24 hours. Forty-one patients with no significant discomfort, 13 patients
      with mild to moderate discomfort. CONCLUSION: Septorhinoplasty and SMD or
      lateralization of inferior turbinate can be managed without packing or any other
      hemostatic measures.

PMID- 18626529
TI  - Factors affecting satisfaction of patients after orthognathic surgery at a
      University Hospital.
AB  - OBJECTIVE: To analyze factors that influence patient's satisfaction with
      orthognathic treatment and evaluate patient's perception of changes in physical
      and psychosocial aspects. METHODS: In a retrospective clinical study conducted at
      Jordan University Hospital, Amman, Jordan between December 2006 and December
      2007, we examined 38 patients who had orthognathic surgery after an average
      follow-up of 20 months. Examination included evaluation of nerve function and
      temporomandibular function with Helkimo index. Patients filled out a
      questionnaire on treatment satisfaction, and perception of physical and
      psychosocial changes after treatment. RESULTS: Patients were generally satisfied
      with the result, 82% agreed they would undergo treatment again. They were divided
      into very satisfied n=25 and less satisfied n=13 groups according to satisfaction
      score, with statistically significant differences found between them concerning
      diagnosis, and follow-up period, with all vertical maxillary excess patients very
      satisfied and 75% of asymmetrical deformities patients less satisfied, and less
      satisfaction by patients more than one year postoperatively p=0.006. Patients
      perceived improvement in oral function, general health, appearance and
      interpersonal skills. Lower rates of joint and muscular pain, and increased
      mobility of lower jaw correlated with better patients' perception of health and
      appearance. CONCLUSION: Although patients' report high satisfaction levels,
      several factors such as the temporomandibular joint function could affect
      patients' psychosocial adjustment after treatment. Sufficient information for
      patients on the treatment course is required to improve satisfaction. Controlling
      these factors could improve patients' quality of life.

PMID- 18626530
TI  - Uncommon locations of hydatid cyst.
AB  - OBJECTIVE: To document the hydatid cyst cases in the endemic Cukurova region of
      Turkey, by their involvement sites in the body, and discuss the clinical and
      morphological features of the cases with rare localization. METHODS: Archival
      materials of 153 hydatid cyst cases that were diagnosed in 2 different medical
      centers in Adana, Turkey Cukurova region between the years 2000-2006 were
      included in the study. Cases with rare localizations were reevaluated in terms of
      clinical and laboratory findings, and histopathological features. Involvement
      sites of the cases were documented, and cases with rare localizations are
      discussed. RESULTS: The liver was the most common localization with 63 cases
      followed by lungs with 54 cases. Uncommon locations were spleen n=4, bone n=3,
      intraarterial n=1, ovary n=1, adrenal n=1, heart n=1, mesenteric n=2,
      retroperitoneal n=2, subcutaneous tissue n=4, breast n=3, intramuscular tissue
      n=4. CONCLUSION: The diagnosis of hydatic cyst should be considered in patients
      with a cystic mass, who live or have lived in a geographic region that has a high
      risk for Echinococcus granulosus, or visited an endemic area.

PMID- 18626531
TI  - Sero-response to measles vaccination at 12 months of age in Saudi infants in
      Qassim Province.
AB  - OBJECTIVE: To evaluate the sero-response to measles component of the first
      measles, mumps and rubella MMR dose given at 12 months by measuring measles
      antibody before and one month after the vaccination. METHODS: A follow-up study
      where, 57 children at the age of 12 months were recruited randomly from the
      Primary Health Care Centers in Qassim, Saudi Arabia using a multistage sampling
      techniques. Fieldwork was conducted from October until December 2006. Blood
      samples were collected to measure measles IgG antibody before, and one month
      after giving MMR using enzyme linked immunosorbent assay. Data were compared
      before and after vaccination using geometric mean titer GMT and seroconversion.
      RESULTS: In the 57 infants, positivity rate increased significantly from 3.5%
      (2/57) pre-vaccination to 100% one month after p=0.0001, and with a sero
      conversion of 96.5% (55/57). Also, GMT increased significantly from 0.014-2.172
      IU/ML, after vaccination p=0.0001. CONCLUSION: Sero conversion and GMT are
      significantly high after the first MMR given at 12 months and this is supported
      by the surveillance data in Qassim.

PMID- 18626532
TI  - Acceptance and compliance of clean intermittent catheterization among Saudi
      patients.
AB  - OBJECTIVE: To determine the applicability, acceptance, and compliance of the
      option of clean intermittent catheterization CIC when needed by patients in our
      society. METHODS: We retrospectively reviewed the files of all patients for whom
      CIC was conducted at King Khalid University Hospital and Security Forces
      Hospital, Riyadh, Saudi Arabia, between 1998, and 2006. We considered primary
      pathology, indication of CIC, age at CIC initiation, and who administered the
      CIC. We also documented the acceptance and compliance levels of the procedure by
      the patient over time. RESULTS: We included 280 patients, of which 118 (42%) were
      female and 162 (58%) were male in this study. The main pathology was
      myelodysplasia in 196 (70%) patients, posterior urethral valve in 52 (18.6%)
      patients, and non-neuropathic bladder sphincter dysfunction in 32 (11.4%)
      patients. The mean age was 6.49 +/- 4.25 years. Two hundred and fifty-seven
      (91.7%) families and their children accepted the idea of CIC, and 248 (88.6%)
      continued with the CIC program. Mothers were responsible for carrying out the
      procedure in 204 (72.9%) patients. However, in 76 (27.1%) cases, the patient was
      doing the procedure independently and the average age for a child to master the
      technique was 8 years. During the last 3 years, an urotherapist took over the
      educational services and performed outpatient education instead of our previous
      inpatient education. CONCLUSION: Clean intermittent catheterization is an
      appropriate method of treatment for our group of patients. They showed excellent
      acceptance of and compliance with the procedure, however, we suggest that for
      complete success, proper education, teaching, and follow-up should be conducted.

PMID- 18626533
TI  - Intravascular catheter colonization and related bloodstream infection in the
      heart surgery intensive care unit.
AB  - OBJECTIVE: To study the incidence of catheter tip colonization, catheter-related
      infections, their risk factors, and to compare these data with other studies.
      METHODS: Since 2006, we have had a through program for the insertion and care of
      all catheters used at cardiac surgical intensive care unit SICU, Tabriz
      University of Medical Sciences, Tabriz, Iran, between May 15, 2006 and September
      15, 2007. We studied prospectively 183 catheters in 150 patients in relation to
      insertion data and catheter characteristics, catheterization time and
      microbiological cultures. These catheters were in place for >48 hours over a 16
      months period. Risk factors were analyzed by multivariate analysis. RESULTS: The
      analysis included 115 central venous catheter CVCs, 65 arterial catheters ACs,
      and 3 pulmonary artery catheters PACs inserted in 150 patients. The median time
      of catheter placement was 4 days. The incidence of positive tip culture was 9.8%
      and 10 microorganism isolated from 18 colonized catheters. Thirteen Gram-negative
      bacilli, 4 Gram-positive cocci, and one yeast were isolated. From multivariant
      analysis, >6 days of catheterization, and insertion site were the variables
      associated with significantly increased risk of catheter colonization.
      CONCLUSION: Gram-negative bacilli and Gram-positive cocci are the most common
      microorganisms colonizing CVC and AC from cardiac SICU patients. Duration of
      catheterization and catheter insertion site were independent risk factors of
      catheter related infection.

PMID- 18626534
TI  - The relation between short-term oral contraceptive consumption and
      cerebrovascular, cardiovascular disorders in Iranian women attending Hajj.
AB  - OBJECTIVE: To evaluate the spectrum of probable vascular complications due to
      short-term oral contraceptives OC consumption. METHODS: In this cohort study,
      selected Iranian female pilgrims from Razavi-Khorasan, Iran province <50 years
      old, attending Hajj in 2005 were evaluated. We reviewed their physical
      examinations, vascular risk factors and OC consumption before Hajj. Pilgrims were
      followed-up in terms of developing possible vascular complications during Hajj
      and the following year. RESULTS: This study included 896 individuals and
      completed follow-up was performed for 642. The results showed that 782 (87.3%) of
      pilgrims used OC. One person developed cerebral vein thrombosis, one myocardial
      infarction, and one deep vein thrombosis. Eighteen patients (2.8%) experienced
      transient hypertension. Ten patients (1.5%) had migraine exacerbations. The
      relationship between developed definite vascular complications and OC consumption
      was not statistically significant in this study p=0.365. CONCLUSION: Although
      vascular complications of long-term OC consumption have been analyzed and proved
      in several studies, few studies have determined short-term OC consumption effects
      on the vascular system. It seems that even short-term usage of OC may result in
      vascular complications, thus further studies with more samples is recommended to
      determine its safety and complications.

PMID- 18626535
TI  - Can deram be a cause of oral lichen planus?
AB  - OBJECTIVE: To study the relationship between oral lichen planus LP and the habit
      of chewing deram. METHODS: A clinically based controlled observational study
      including a total of 176 women who used to chew deram and 200 women who never
      used deram, who consulted the Dermatology Department of Basrah Teaching Hospital,
      and a private clinic, Barsah, Iraq during the period from February 2005 to July
      2007. RESULTS: The study showed that the incidence of oral LP is greater among
      176 deram chewers (23.3%) in comparison with 200 women who never use deram
      (1.5%), particularly among those with frequent (51.2%) and prolonged (65.8%)
      chewing of deram. Oral lesions, were mostly asymptomatic (80.5%) and
      predominantly of reticulate pattern (87.9%). Avoidance of deram chewing induced
      marked or complete improvement of the oral lesions in 56.3% of cases even without
      treatment within a 3 month follow up period. Pathological examination showed
      features similar to classical LP. CONCLUSION: Deram chewing should be considered
      as a possible cause of oral LP, particularly among frequent and prolonged
      chewers.

PMID- 18626537
TI  - Awareness and behavior about Pap smear testing in family medicine practice.
AB  - OBJECTIVE: To describe and estimate the effect of 5 socio-demographic variables
      and insurance status on awareness of pap smear, and the influence of
      sociodemographic characteristics, health insurance and knowledge score on having
      a pap smear test. METHODS: This is a cross-sectional study of 674 female
      patients, aged 17 years and above between October and December 2006, and
      attending family medicine clinics at Jordan University Hospital, Amman, Jordan.
      We collected data on socio-demographic factors, future intention to take the test
      and barriers to screening. RESULTS: Of 674 patients, 68.1% were aware of the Pap
      smear as a medical test. Of married women, 40.3% had a screening history. Women
      who were aware of the test were more likely to be <35 years of age, married, and
      have higher than secondary education. Women who have had a Pap test were younger
      and had higher knowledge scores of the Pap smear. The physicians were the main
      source of information regarding awareness and having the test. Female physicians,
      particularly gynecologists, were preferred to perform the Pap smear. Fear of the
      procedure and the results of the test were the major obstacles to having the
      test. CONCLUSION: There is an imminent need for an awareness campaign; a simple 5
      item knowledge test can identify a group of women, who can most benefit from
      targeted interventions.

PMID- 18626536
TI  - The survival analysis of beta thalassemia major patients in South East of Iran.
AB  - OBJECTIVE: To determine the survival of beta-thalassemia major patients with
      transfusion, and its related factors in Southeast of Iran. METHODS: This cross
      sectional study was performed in Zahedan, Iran, in 2007. The sample included
      patients who were referred from all over the Zahedan Thalassemia Center from 1998
      to 2006. The data were collected using the patients' records, which were recorded
      by the staff during transfusion. The data included demographic and medical
      information blood group, blood RH, the kind of transfused blood [KTB], annual
      number of transfusions [ANOT], accompanied diseases [AD], Hemoglobin [Hb] and
      ferritin level. For data analysis, the Kaplan-Meyer method, and Log Rank test
      together with Cox Regression were used. RESULTS: Forty-six of 578 patients died
      and 99% had survived for the first year. The ages survival proportions were 5
      (97.9%), 10 97%, 15 (92.1%), and 20 (81.2%) years. The survival time showed
      significant relationships with the ANOT p=0.0053, KTB p=0.003, Hb p=0.002 and
      ferritin level p=0.0087, and AD p=0.000. CONCLUSION: Using regular transfusion,
      paying attention to screening of transfused blood, increasing the families'
      knowledge on the disease to prevent the bearing of thalassemia fetus, are
      recommended; finally, the detection and treating of the AD, are of great
      importance to extend the lifetime of the patients.

PMID- 18626538
TI  - Cardiac metastasis in malignant fibrous histiocytoma.
AB  - Malignant fibrous histiocytoma MFH is an aggressive spindle cell cancer and is
      the most common soft tissue tumor in the elderly, primarily affecting the
      extremities. It has high metastatic potential and can spread to various viscera
      including liver, lung, bone, and brain; however, cardiac metastasis is an extreme
      rarity. Here, we present a 50-year-old male, diagnosed as pleiomorhphic storiform
      MFH a of right arm who developed parenchymal pulmonary metastases and a mass
      lesion in left atrium. Patient had a downhill course and eventually succumbed.

PMID- 18626539
TI  - Endometrioid adenocarcinoma 13 years after total abdominal hysterectomy and
      bilateral salpingo-oophorectomy.
AB  - Malignant transformation is an infrequent complication of endometriosis. As
      endometriosis is an ectopic endometrium, hyperestrogenism may cause hyperplasia
      or transformation into cancer. We describe a case of a 68-year-old woman who
      underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for
      endometriosis. She was subsequently placed on estrogen-only replacement therapy.
      She presented with left-sided pelvic mass and shortness of breath. Computed
      tomography of chest, pelvis, and abdomen, demonstrated right-sided pleural
      effusion and soft tissue mass in the pelvis. Pleural effusion was tapped and
      biopsy from the peritoneal mass showed metastatic adenocarcinoma;
      immunohistochemistry findings favored endometrioid adenocarcinoma. She was
      treated by 6 cycles of Carboplatin/Paclitaxel and responded well. Unopposed
      estrogen stimulation may lead to premalignant or malignant transformation in the
      residual foci of endometriosis. Therefore, the addition of progestins to estrogen
      replacement therapy should be considered in women who have undergone hysterectomy
      with oophorectomy due to endometriosis.

PMID- 18626540
TI  - Burkholderia gladioli associated abscess in a type 1 diabetic patient.
AB  - Burkholderia gladioli, a bacterial pathogen, causes a variety of infectious
      ailments in immunocompromised individuals. We present a case report of foreign
      body associated Burkholderia gladioli related abscess in an immunocompetent type
      1 diabetic patient. Relevant medical literature is reviewed to understand this
      unusual mode of presentation of this bacterium in our patient.

PMID- 18626541
TI  - Multi-drug resistant Ewingella americana.
AB  - We report a case of pneumonia due to multi-drug resistant Ewingella americana in
      a young patient admitted in the Intensive Care Unit of Hera General Hospital,
      Makkah, Saudi Arabia with severe head injury in a road traffic accident. He was
      an Indonesian pilgrim who had traveled to the Kingdom of Saudi Arabia to perform
      Hajj in December 2007. Ewingella americana was identified to be the pathogen of
      pneumonia with clinical signs and symptoms along with positive radiological
      findings.

PMID- 18626542
TI  - Primary angiosarcoma arising from a multicystic kidney.

PMID- 18626543
TI  - Determination of liver enzymes, serum ceruloplasmin and urine copper in parents
      of children with Wilson's disease.

PMID- 18626544
TI  - Vaccine - associated paralytic poliomyelitis in a pre-vaccinated infant.

PMID- 18626545
TI  - A neglected cause of cervical lymphadenitis. Oropharyngeal tularemia.

PMID- 18626546
TI  - Sputum eosinophil markers in monitoring asthmatic patients in United Arab
      Emirates.

PMID- 18626547
TI  - Continuous positive airway pressure compliance in Saudi men and women with sleep
      apnea.

PMID- 18626548
TI  - A rare cause of recurrent dyspnea.

PMID- 18626549
TI  - Bacille Calmette-Guerin immunotherapy of viral warts.

PMID- 18626550
TI  - Need for more environmental control of Klebsiella and other gram negative
      infections.

PMID- 18626555
TI  - Mental disorders and mental health care in Canada and Australia: comparative
      epidemiological findings.
AB  - BACKGROUND: Canada and Australia although geographically distant have
      similarities in human geography and history. Each has had a national mental
      health policy for some years, but Australia has driven policy implementation in
      this area harder than has Canada. Comparable epidemiological surveys from
      Australia in 1997 and Canada in 2002 allow us to explore relative rates of mental
      disorders and compare estimates of access to care from mental health services.
      METHODS: We compare findings from the Australian National Survey of Mental Health
      and Wellbeing (1997) with those from the Canadian Community Health Survey on
      Mental Health and Well Being, cycle 1.2 (2002). RESULTS: Differences in
      prevalence rates and in service utilisation emerge between the two countries:
      Anxiety Disorders are estimated as almost 2% higher in Canada than in Australia
      while there is suggestion that Major Depressive Disorder, Alcohol Dependence and
      Drug Dependence may be more prevalent in Australia. More of the people with co
      morbid disorders in Australia than in Canada make use of mental health services
      and a finding of marginal significance suggests that this may be true across all
      disorders. CONCLUSIONS: Causation cannot be determined from this study but
      possible explanations for differences in prevalence include changes in global
      economic, political and security contexts and concerns between 1997 and 2002 and
      the possible role of greater availability of alcohol in Australia. The findings
      also provide encouragement that strenuously implementing a national mental health
      policy may have been of benefit to people with mental health problems in
      Australia.

PMID- 18626556
TI  - Practice patterns and treatment choices among psychiatrists in New Delhi, India:
      a qualitative and quantitative study.
AB  - OBJECTIVE: Several issues relevant to the care of Asian Indian patients remain
      poorly explored. Little is known about the practice patterns of psychiatrists in
      India, such as daily practice routines or treatment approaches, which we describe
      in New Delhi, India. METHODS: We focused on psychiatric practice, as perceived by
      Indian psychiatrists, using a sample from the USA as a comparison group. We used
      triangulated, qualitative methods from data gathered in India (ethnographic
      interviews with 16 Delhi psychiatrists, observation of treatment in India, and
      treatment of Indian patients) to design and validate a survey distributed to a
      sample of 34 psychiatrists in New Delhi and 34 in Baltimore, Maryland who treat
      Indian patients. RESULTS: Delhi psychiatrists saw more patients daily (24.3 vs.
      11, P<0.001), and spent less time on new evaluations (33.3 vs. 69 min, P<0.001).
      Both groups had similar approaches to major disorders. But, Delhi psychiatrists
      were less likely to combine medication treatment with psychotherapy (P<0.05), and
      more likely to advise families to secretly administer medications in treatment
      refusal, such as in acute schizophrenia (P<0.001) or major depression (P<0.01).
      CONCLUSIONS: These differences highlight the salience of local cultural context
      in the practice of psychiatry and in the treatment of Indian patients. Delhi
      psychiatrists are overwhelmed by the epidemic levels of untreated illness, spend
      less time with patients, and rely more heavily on medication treatment. Delhi
      psychiatrists employ unique approaches to handling difficult treatment issues,
      such as treatment refusal, intensive involvement of the family, and
      recommendations to the family about suitability for marriage for a patient.

PMID- 18626557
TI  - Is low IQ associated with an increased risk of developing suicidal thoughts? A
      cohort study based on an 18-month follow-up of the national psychiatric morbidity
      survey.
AB  - BACKGROUND: Studies in young male conscripts suggest that low IQ scores are
      associated with an increased risk of suicide. Mechanisms underlying this
      association are unclear. AIM: To investigate the association of IQ, as indexed by
      the national adult reading test (NART), with the incidence of, and recovery from,
      suicidal thoughts. METHOD: An 18-month follow-up of 2,278 of the adults who took
      part in the Britain's second national psychiatric morbidity survey who completed
      the NART at baseline. RESULTS: There was no evidence that poor performance on the
      NART was associated with an increased incidence of suicidal thoughts over the 18
      month follow-up (adjusted odds ratio per 10 unit increase in NART-IQ 1.08 (95% CI
      0.86-1.36). However, amongst the 155 subjects with suicidal thoughts at baseline,
      those with low NART-IQ were least likely to recover from them: the adjusted odds
      of recovery per 10 unit increase in NART-IQ was 1.42 (95% CI 0.96-2.10).
      CONCLUSION: The association between low IQ and an increased risk of suicide may
      be because people with low IQ experience suicidal thoughts for more prolonged
      periods than those with high IQ or because low IQ increase the likelihood that
      people experiencing suicidal thoughts act upon them.

PMID- 18626558
TI  - Evaluation of chromosome aberrations in subjects exposed to environmental tobacco
      smoke in Tamilnadu, India.
AB  - Numerous expert panels have concluded that there is sufficient evidence to
      classify involuntary smoking (or passive smoking) as carcinogenic to humans. The
      aim of this study is to establish whether passive smoking increases the frequency
      of chromosomal aberrations (CA) in peripheral blood lymphocytes compared to
      controls in Tamil Nadu, India. In the present study, CA increased with an
      increase in environmental tobacco smoke (ETS) and active smoke exposure period in
      passive smokers quantified on the basis of serum cotinine levels. The passive
      subjects were compared with healthy normal controls to validate the results. In
      conclusion, these data are compatible with the current knowledge on the
      mechanisms of carcinogenesis of tobacco-related cancers, occurring not only in
      active smokers but with a high biological plausibility also in passive smokers.

PMID- 18626559
TI  - Organic pollutants in areas impacted by flooding in 2002: a 4-year survey.
AB  - This paper summarizes a 4-year survey focused on polycyclic aromatic hydrocarbons
      (PAHs) and halogenated persistent organic pollutants (POPs) in river sediments,
      soil and crops collected in the locality impacted by catastrophic floods that
      occurred in the western part of Bohemia in August 2002. In spite of relatively
      high levels of polychlorinated biphenyls (PCBs) in river sediments, the increase
      of these POPs in flooded arable soil was not significant. On the other hand,
      remarkably higher levels of PAHs and dichlorodiphenyl trichloroethane (DDTs) were
      found as compared to those in reference soil samples. Regardless of this
      increased soil pollution, no measurable elevated concentrations of POPs occurred
      in the wheat grown in this area.

PMID- 18626560
TI  - Influence of elevated carbon dioxide and ozone on the foliar nonvolatile
      terpenoids in ginkgo biloba.
AB  - The aim of this study was to determine the effects of elevated O(3) and elevated
      CO(2,) singly and in combination, on the contents of nonvolatile terpenoids in
      leaves of Ginkgo Biloba. The results showed that elevated CO(2), alone and in
      combination with elevated O(3) increased concentrations of all the determined
      terpenoids, while elevated O(3) alone only increased concentration of bilobalide.
      These results demonstrated that the metabolism of terpenoids in ginkgo leaves was
      more sensitive to elevated CO(2) than elevated O(3).

PMID- 18626561
TI  - DDT and HCH isomer levels in soils, carrot root and carrot leaf samples.
AB  - Agricultural cultivation assists organochlorine pesticide migration from
      contaminated soils to growing plants. This phenomenon is caused by retention
      processes that modify volatile pesticide exchange between soil, air and plants.
      The aim of the study was to monitor organochlorine pesticide (HCB, alpha- and
      gamma-HCH, pp'DDE, op'DDT, pp'DDT) levels and compare these concentrations in
      soil, carrot roots and carrot leaves. Fifty soil samples, 50 carrot root and 50
      carrot leaf samples were taken from the same fields and analyzed by GLC-ECD. The
      results reveal organochlorine pesticide diffusion from agricultural soils to
      growing carrot plants and their vapors adsorption by leaves. Within the carrot
      plant, organochlorine pesticides accumulate especially in carrot root peel, 3-7
      times more than in root flesh.

PMID- 18626562
TI  - Seasonal occurrence of vibrios in water and shellfish obtained from the Great Kwa
      River estuary, Calabar, Nigeria.
AB  - The prevalence of Vibrio species in shellfish and their seasonal variability in
      the Great Kwa River estuary (GKWE) were examined. Results revealed a trimodal
      peak in Vibrio counts, coinciding with meteorological changes and the hot periods
      of the year. The estuary was constantly faecally polluted, coupled with high
      rates of infection of shellfish by V. parahaemolyticus 42 (13.6%), V. cholerae
      non-01 29 (9.4%) and V. alginolyticus 22 (7.1%), thus posing a health risk. The
      observed seasonal variability and prevalence of Vibrio species infection are of
      epidemiological significance, and provide a guide for effective control of
      associated cholera epidemics.

PMID- 18626563
TI  - Absorption of semiconductor nanocrystals by the aquatic invertebrate Ceriodaphnia
      dubia.
AB  - When incubated with nanomolar concentrations of fluorescent semiconductor
      nanocrystals in moderately hard water the fluorescence of living Ceriodaphnia
      dubia increased. Average pixel intensity of exposed animals was greater than that
      of unexposed animals and increased in a dose and exposure time-dependent-manner.
      Internal structures were clearly visible in exposed and unexposed animals but
      fluorescence was most intense in the region of the abdominal appendages of
      exposed animals. Since these nanoparticles contain significant quantities of the
      toxic metals cadmium and selenium, their accumulation from aquatic environments
      by this standard test organism has significant implications about their potential
      environmental toxicity.

PMID- 18626564
TI  - Assessment of extractants for the determination of thallium in an accidentally
      polluted soil.
AB  - Thallium is a rare and easily dispersed element with high toxicity to organisms.
      Relatively high levels of thallium (approximately 9.58 mg kg(-1)) had been found
      in aqua regia soil extract of an accidentally polluted soil from south of Spain.
      To assess the available and leachable portions of thallium in the polluted soil,
      single and sequential extraction procedures have been utilized. Further, X-ray
      diffraction and scanning electron microscopic studies have also been used to find
      out the mineral phases. The amount of thallium extracted by the extracting agents
      in comparison to aqua regia, as well as the different phase associations are
      discussed.

PMID- 18626565
TI  - Cell cycle stage specific application of cypermethrin and carbendazim to assess
      the genotoxicity in somatic cells of Hordeum vulgare L.
AB  - In this study, the genotoxicity of commonly used insecticide cypermethrin and
      fungicide carbendazim were examined on root meristem cells of Hordeum vulgare L.
      Cypermethrin and carbendazim were applied with concentrations of 0.05%, 0.1% and
      0.5% at different presoaking durations of 7 h, 17 h and 27 h which falls into
      G(1), S and G(2) phases of cell cycle, respectively. The cytogenetic studies of
      the root meristem cells of Hordeum vulgare L. showed that S phase of the cell
      cycle was more sensitive in comparison to other phases of cell cycle.

PMID- 18626566
TI  - Parathyroid hormone(1-84) treatment of postmenopausal women with low bone mass
      receiving hormone replacement therapy.
AB  - Treatment of postmenopausal osteoporosis (PMO) is based primarily on
      antiresorptive agents, including hormone replacement therapy (HT). To evaluate
      whether anabolic therapy together with HT provides additional benefits in the
      treatment of PMO, we evaluated the effects of parathyroid hormone (PTH) 1-84 in
      postmenopausal women with low bone mineral density (BMD) who were receiving
      chronic (> or =6 months) HT. Subjects were randomized to receive 100 microg PTH(1
      84) or placebo injections daily for 24 months (n = 90/group). The primary
      efficacy outcome was change from baseline in lumbar spine BMD. Secondary end
      points included changes in hip and distal radius BMD, bone turnover markers, and
      fracture incidence. The study was terminated early following recommendations
      regarding HT for PMO. At 18 months, the mean increase in lumbar spine BMD was
      7.9% for PTH(1-84) subjects vs. 1.5% for those receiving HT alone; between-group
      differences were significant at 6 months and persisted throughout the study.
      Lumbar spine BMD increased in 94% of women receiving PTH(1-84) compared to 59%
      for HT alone. Femoral neck BMD and bone turnover markers were significantly
      higher in PTH(1-84)-treated subjects, but the changes in total hip and distal
      radius BMD were not significant. PTH(1-84) treatment was generally well
      tolerated, with hypercalciuria, hypercalcemia, nausea, vomiting, and dizziness
      reported more frequently in the HT + PTH(1-84) group. In conclusion, addition of
      PTH(1-84) to stable HT produced marked increases in lumbar spine BMD and may
      represent an additional approach to the treatment of PMO women receiving HT.

PMID- 18626567
TI  - Antigenic characterization of bovine ephemeral fever rhabdovirus G and GNS
      glycoproteins expressed from recombinant baculoviruses.
AB  - Recombinant baculoviruses expressing the BEFV envelope glycoprotein G and non
      structural glycoprotein G(NS) were constructed. The G protein expressed in insect
      cells was located on the cell surface and induced spontaneous cell fusion at
      mildly acidic pH. The expressed G protein reacted with MAbs to continuous and
      conformational neutralization sites (G1, G2, G3b and G4), but not to
      conformational site G3a. The expressed G(NS) protein was also located on the cell
      surface but did not exhibit fusogenic activity. The G(NS) protein reacted with
      polyclonal antiserum produced from vaccinia-virus-expressed recombinant G(NS) but
      did not react with G protein antibodies. A His(6)-tagged, soluble form of the G
      protein was expressed and purified by Ni(2+)-NTA chromatography. The purified G
      protein reacted with BEFV-neutralizing MAbs to all continuous and conformational
      antigenic sites. The highly protective characteristics of the native BEFV G
      protein suggest that the secreted, baculovirus-expressed product may be a useful
      vaccine antigen.

PMID- 18626568
TI  - Role of the DxxDxD motif in the assembly and stability of betanodavirus
      particles.
AB  - Piscine betanodavirus possesses a bipartite genome of single-stranded (+)RNAs.
      RNA2 cDNA of dragon grouper nervous necrosis virus (DGNNV) has been expressed
      previously to form virus-like particles (VLPs), which are highly similar to the
      native virion. Experiments with calcium-chelating or reducing/oxidizing reagents
      showed that the DGNNV VLPs required only calcium for particle assembly. With the
      recombinant VLPs, site-directed mutagenesis can be employed to investigate the
      roles of calcium-binding ligands in particle formation. The results of mutational
      analysis of DxxDxD, which is putatively involved in the coordination of calcium
      ions, showed that the D133N mutation significantly disrupted the assembly of
      VLPs, while D130N and D135N mutants produced heterogeneous VLPs with broken
      shapes. The thermal stability of the VLP-forming fractions demonstrated that VLPs
      of the D135N mutant were stable at a temperature of 85 degrees C, which is
      slightly higher than that for wild-type, whereas VLPs of the D130N mutant could
      not tolerate the thermal effects at a temperature higher than 60 degrees C. It
      was deduced that the three aspartate residues of the motif DxxDxD are all
      important for the efficient formation of DGNNV VLPs and that, among them, the
      DxxD provides a more stable coordinate of calcium ligand than DxD.

PMID- 18626569
TI  - VSX1 gene variants are associated with keratoconus in unrelated Korean patients.
AB  - Keratoconus is a bilateral ectatic disorder characterized by the central thinning
      of corneal tissue leading to visual impairment. To investigate the possibility of
      visual system homeobox 1 (VSXI) as a candidate susceptibility gene for Korean
      patients with keratoconus, we performed a mutation screening of the VSXI gene in
      249 unrelated patients with keratoconus and 208 control subjects without the
      ocular disorder. We found two heterozygous novel missense mutations in exon 2:
      N151S and G160V. The G160V mutation was identified in 13 keratoconus patients
      (5.3%), and the N151S mutation was found in only one keratoconus patient (0.4%).
      We also detected three synonymous polymorphisms and four intragenic
      polymorphisms. The IVS1-11*a allele was associated with a significantly increased
      risk of keratoconus in Korean patients [3.6 vs. 0.5%, p = 0.001, odds ratio (OR)
      = 7.76, 95% confidence interval (CI) 1.989-30.241). Other polymorphisms did not
      show an association with keratoconus risk. Our data is the first reported VSX1
      mutation screening in Korean keratoconus patients. We detected two novel missense
      mutations and one intragenic polymorphism in the VSX1 gene, which show a strong
      statistical association with unrelated keratoconus patients. Consequently, our
      study suggests that VSX1 gene variants seem to be significant genetic variants
      for keratoconus predisposition in unrelated Korean patients.

PMID- 18626570
TI  - Effect of soft laser and bioactive glass on bone regeneration in the treatment of
      bone defects (an experimental study).
AB  - This study aimed to investigate the influence of low-power gallium-aluminium
      arsenide (GaAlAs) laser [830 nm, continuous wave (CW), 40 mW and fluence 4
      J/cm(2)] on the healing of surgically created bone defects in rats treated with
      bioactive glass graft material. Surgical bone defects were created in the
      mandibles of 36 Wistar rats divided into two groups, each consisting of 18 rats.
      Group I was treated with bioactive glass plus laser irradiation. Group II was
      treated with graft material only. The animals were killed at 4 weeks, 8 weeks and
      12 weeks postoperatively for histological examination. Laser irradiation had
      significantly accelerated bone healing at 4 weeks and 8 weeks in comparison with
      that at the sites not irradiated. However at 12 weeks, complete healing of the
      defects had occurred with no difference detected. Our results have confirmed the
      positive effect of soft laser in accelerating bone regeneration.

PMID- 18626571
TI  - Intense pulsed light photoepilation in hirsute women: the role of obesity.
AB  - Intense pulsed light (IPL) has shown diverse results in hair clearance related to
      treatment protocols or skin phototype. Hirsutism may be due to endocrine disease,
      as in polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH),
      both of which conditions may be associated with obesity. Obesity complicates the
      metabolic pattern, particularly in terms of insulin resistance, which may worsen
      the clinical condition of hirsutism. This study evaluated the role of obesity in
      photoepilation, comparing the clinical efficacy, long-term hair reduction and
      patient satisfaction in 40 hirsute women with PCOS or CAH, either obese (n = 20)
      or of normal weight (n = 20). The IPL settings were the same for both groups, but
      the number of sessions varied according to the clinical results. Obese patients
      showed a statistically significant severity of initial hirsutism if compared to
      the non-obese population and, for this reason, required more sessions to achieve
      hair reduction. The results were maintained at the 2-year follow-up examination,
      with a high satisfaction rate in both groups.

PMID- 18626572
TI  - Phase I trial of weekly docetaxel and daily temozolomide in patients with
      metastatic disease.
AB  - Docetaxel is second generation taxoid that has shown activity against a variety
      of cancers and has been approved for use in cancers of the breast, lung, head and
      neck, ovaries and prostate. Temozolomide is an alkylating agent which crosses the
      blood brain barrier and has demonstrated antitumor activity against a broad range
      of tumor types, including malignant glioma, melanoma, non small cell lung cancer
      and carcinoma of the ovary and colon. A Phase I trial was conducted to determine
      the toxicity of this combination in refractory solid tumor patients. METHODS:
      Twenty five patients with metastatic cancers were enrolled in a Phase I dose
      escalation trial. Docetaxel was administered weekly in 5 escalating doses of 25
      to 35 mg/ m(2) as a one-hour bolus intravenous infusion for 3 consecutive weeks.
      Temozolamide was administered orally daily for 3 weeks (escalating doses of 75 to
      100 mg/m(2)). Cycles were repeated at 4 week intervals. RESULTS: The maximum
      tolerated dose (MTD) was not determined in this study. The most commonly reported
      adverse events were mild to moderate nausea, vomiting and fatigue.
      Thrombocytopenia was the most commonly observed grade 3 and 4 hematological
      toxicity. Eight patients had dose interruptions for adverse events and only one
      patient had a dose reduction while receiving 30 mg/ m(2) of docetaxel and 90 mg/
      m(2) of temozolomide due to grade 3 thrombocytopenia. Two patients achieved
      partial responses and 88% of the patients are deceased. The median survival is
      8.4 months. CONCLUSIONS: The combination of docetaxel and temozolomide was well
      tolerated and these agents can be safely combined. For phase II trials, docetaxel
      35 mg/ m(2) IV day 1, 8 and 15, and daily temozolomide at 100 mg/ m(2) day 1-21
      are recommended.

PMID- 18626573
TI  - Molecular imaging of epidermal growth factor receptor expression-activity at the
      kinase level in tumors with positron emission tomography.
AB  - Because of the importance of epidermal growth factor receptor (EGFR) signaling
      pathway in oncogenesis, maintenance, and progression of different types of
      tumors, there has been an intense effort to develop non-invasive imaging
      approaches for selection and monitoring of EGFR-targeted therapies. During the
      past decade, EGFR-tyrosine kinase inhibitors have been explored as potential
      radiotracers for positron emission tomography (PET) imaging of EGFR over
      expressing tumors. The development of agents for PET imaging of EGFR at the
      tyrosine kinase level has been so far based exclusively on anilinoquinazoline
      core structure, which has been "borrowed" as the key pharmacophore from the
      leading EGFR-inhibitory pharmaceuticals. The I-124, F-18, and C-11 radiolabeled
      irreversible inhibitors of EGFR demonstrate the greatest potential for
      derivatization into effective EGFR kinase imaging agents. PET imaging with
      radiolabeled agents specific for activated forms of EGFR kinase will facilitate
      the selection (stratification) of patients which will have more favorable
      responses to therapy with EGFR signaling inhibitors.

PMID- 18626574
TI  - Retinal pigment epithelium detachment associated with vitreomacular traction
      syndrome-case report.
AB  - PURPOSE: To report the unusual association of vitreomacular traction syndrome
      (VMT) with retinal pigment epithelium (RPE) detachment and describe the outcomes
      of successful surgery. METHODS: An 84-year-old man was referred with 6-month
      history of blurred vision in his RE. Best-corrected visual acuity (BCVA) was
      "counting fingers." Slit-lamp examination revealed VMT overlying a RPE
      detachment. The above findings were confirmed by optical coherence tomography
      (OCT). Pars plana vitrectomy and internal limiting membrane (ILM) peeling were
      performed. OCT was carried out at 3, 6, 9, and 11 months postoperatively.
      RESULTS: Eight weeks postoperatively BCVA improved to 6/60. Slit-lamp examination
      and OCT showed relief of the vitreomacular traction, however the underlying RPE
      detachment remained unchanged and progressively regressed during the following 11
      months. Visual acuity did not improve above 6/36 at the last follow-up visit.
      CONCLUSION: Retinal pigment epithelium detachment could be associated with VMT.
      Although the incidence is rare, it may compromise the outcomes of successful
      surgery.

PMID- 18626575
TI  - FOXP3 and its partners: structural and biochemical insights into the regulation
      of FOXP3 activity.
AB  - Forkhead box protein P3 (FOXP3) contributes to a unique transcriptional signature
      and serves as a functional marker of CD4(+)CD25(+) natural regulatory T cells.
      Dysfunction of FOXP3 in human is associated with fatal autoimmune disease known
      as immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)
      or X-linked autoimmunity-allergic disregulation syndrome (XLAAD). FOXP3 also can
      act as a breast tumor suppressor of the v-erb-b2 erythroblastic leukemia viral
      oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog (avian))
      (Her2/neu) gene. While the suppressive functions of FOXP3 in maintaining the
      immune balance between tolerance and autoimmunity are obvious, the underlying
      molecular mechanism remains almost entirely undefined. Recent studies indicate
      that FOXP3 may form a dynamic superamolecular complex with a variety of molecular
      partners including transcription factors and enzymatic proteins to regulate
      transcription. How the FOXP3 ensemble changes in response to T-cell receptor
      signals and/or proinflammatory signal remains unclear although work from this
      laboratory has revealed its complexity. Structural information on FOXP3 complex
      may offer novel functional insights, as well as facilitate the development of
      rational means to modulate regulatory T-cell function in various human diseases.

PMID- 18626577
TI  - Influence of high solid concentration on enzymatic hydrolysis and fermentation of
      steam-exploded corn stover biomass.
AB  - Steam-exploded corn stover biomass was used as the substrate for fed-batch
      separate enzymatic hydrolysis and fermentation (SHF) to investigate the solid
      concentration ranging from 10% to 30% (w/w) on the lignocellulose enzymatic
      hydrolysis and fermentation. The treatment of washing the steam-exploded material
      was also evaluated by experiments. The results showed that cellulose conversion
      changed little with increasing solid concentration, and fermentation by
      Saccharomyces cerevisiae revealed a nearly same ethanol yield with the water
      washed steam-exploded corn stover. For the washed material at 30% substrate
      concentration, i.e., 30% water insoluble solids (WIS), enzymatic hydrolysis
      yielded 103.3 g/l glucose solution and a cellulose conversion of 72.5%, thus a
      high ethanol level up to 49.5 g/l. With the unwashed steam-exploded corn stover,
      though a cellulose conversion of 70.9% was obtained in hydrolysis at 30% solid
      concentration (27.9% WIS), its hydrolysate did not ferment at all, and the
      hydrolysate of 20% solid loading containing 3.3 g/l acetic acid and 145 mg/l
      furfural already exerted a strong inhibition on the fermentation and ethanol
      production.

PMID- 18626576
TI  - The IkappaB kinase complex: master regulator of NF-kappaB signaling.
AB  - The Nuclear Factor-kappa B (NF-kappaB) family of transcription factors regulates
      the expression of a wide range of genes critical for immune and inflammatory
      responses, cell survival, immune development, and cell proliferation.
      Dysregulated NF-kappaB activity occurs in a number of chronic inflammatory
      diseases and certain types of cancers making NF-kappaB signaling an attractive
      target for the development of anti-inflammatory and anti-cancer drugs. A pivotal
      regulator of all inducible NF-kappaB signaling pathways is the IkappaB kinase
      (IKK) complex that consists of two kinases (IKKalpha and IKKbeta) and a
      regulatory subunit named NF-kappaB essential modulator (NEMO). Genetic analysis
      of the IKK complex has identified two separate pathways named the classical and
      non-canonical mechanisms that are dependent on either NEMO and IKKbeta
      (classical) or IKKalpha alone (non-canonical). To better understand the
      mechanisms that regulate IKK complex activity and to address the differential
      functions of IKKalpha and IKKbeta we have molecularly dissected the IKKs. We
      describe here how these studies have identified a unique inhibitor of pro
      inflammatory NF-kappaB signaling, an unforeseen role for IKKalpha in the
      classical NF-kappaB pathway, and a novel functional domain in IKKbeta that is not
      present in IKKalpha.

PMID- 18626578
TI  - Cloning, protein sequence clarification, and substrate specificity of a leucine
      dehydrogenase from Bacillus sphaericus ATCC4525.
AB  - Although an X-ray model sequence of a leucine dehydrogenase from Bacillus
      sphaericus ATCC4525 was reported, the amino acid sequence of this enzyme has not
      been confirmed. In the current study, this leucine dehydrogenase gene was cloned,
      sequenced, and over-expressed in Escherichia coli, and the protein sequence has
      been clarified. This leucine dehydrogenase is not identical with that of B.
      sphaericus IFO3525 because there are 16 different amino acid residues between
      these two proteins. Since the information on the catalytic properties of leucine
      dehydrogenase from B. sphaericus ATCC4525 has been limited, the recombinant
      enzyme was purified as His-tagged protein and further studied. This enzyme showed
      activity toward aliphatic substrates for both oxidative deamination and reductive
      amination and is an effective catalyst for the asymmetric synthesis of alpha
      amino acids from the corresponding alpha-ketoacids.

PMID- 18626579
TI  - Kinetic analysis and pH-shift control strategy for propionic acid production with
      Propionibacterium Freudenreichii CCTCC M207015.
AB  - The production of propionic acid by Propionibacterium freudenreichii CCTCC
      M207015 was investigated in a 7.5-l stirred-tank fermentor. Batch fermentations
      by P. freudenreichii CCTCC M207015 at various pH values ranging from 5.5 to 7.0
      were studied. Based on the analysis of the time course of specific cell growth
      rate (mu (x)) and specific propionic acid formation rate (mu (p)), a two-stage pH
      shift control strategy was proposed. At first 48 h, pH was controlled at 6.5 to
      obtain the maximal mu (x), subsequently pH 6.0 was used to maintain high mu (p)
      to enhance the production of propionic acid. By applying this pH-shift control
      strategy in propionic acid fermentation, the maximal propionic acid and glucose
      conversion efficiency had a significant improvement and reached 19.21 g/l and
      48.03%, respectively, compared with those of constant pH operation (14.58 g/l and
      36.45%). Fed-batch fermentation with pH-shift control strategy was also applied
      to produce propionic acid; the maximal propionic acid yield and glucose
      conversion efficiency reached 25.23 g/l and 47.76%, respectively.

PMID- 18626580
TI  - Effect of cultural conditions and media constituents on production of penicillin
      V acylase and CTAB treatment to enhance whole-cell enzyme activity of Rhodotorula
      aurantiaca (NCIM 3425).
AB  - Penicillin V acylase (PVA) is a pharmaceutically important enzyme as it plays a
      vital role in the manufacture of semi-synthetic beta-lactam antibiotics.
      Rhodotorula aurantiaca (NCIM 3425) produced high levels of intracellular
      penicillin V acylase after 18 h at pH 8.0 and temperature 27 degrees C. Fructose
      was the best carbon source for PVA production, whereas tryptone was the best
      nitrogen source to produce the enzyme up to 170 and 1,088 IU/l of culture,
      respectively. Additionally, the cell-bound PVA activity was enhanced on treatment
      with cationic detergent. Whole-cell activity was found to be doubled (204%) on
      treatment of 0.01 g dry weight of cells with 50 microg/ml solution of N-cetyl
      N,N,N-trimethylammoniumbromide at pH 8.0 for 1 h at room temperature. Atomic
      force microscopy images of permeabilized cells show perturbation in the cell wall
      and offer first-ever visual illustration of surface structure modifications that
      occur during permeabilization of R. aurantiaca cells leading to enhancement in
      activity of intracellular enzyme.

PMID- 18626581
TI  - Exploring antagonistic metabolites of established biocontrol agent of marine
      origin.
AB  - Biocontrol ability of Pseudomonas aeruginosa ID 4365, a biocontrol agent of
      groundnut phytopathogens from marine origin, was previously attributed to the
      production of pyoverdin type of siderophores. However, pyoverdin-rich
      supernatants of this organism showed better antifungal activity compared to
      equivalent amount of purified pyoverdin indicating presence of undetected
      metabolite(s) in pyoverdin rich supernatants. On the basis of observation that
      antagonistic activity was iron-dependent and iron-independent, an attempt was
      made to detect the presence of additional metabolites. In addition to pyoverdin,
      strain produced additional siderophores, viz. pyochelin and salicylic acid. Two
      broad spectrum antifungal compounds, viz. pyocyanin and phenazine-1-carboxylic
      acid, were detected, characterized, and activity against phytopathogens was
      demonstrated. Iron- and phosphate-dependent co-production of siderophores and
      phenazines was confirmed. Strain showed additional features like production of
      hydrogen cyanide, indol-3-acetic acid, and phosphate solubilization.

PMID- 18626582
TI  - New thermostable amylase from Bacillus cohnii US147 with a broad pH
      applicability.
AB  - A new thermophilic bacterial strain identified as Bacillus cohnii US147 was
      isolated from the southern Tunisian soil. The identification was based on
      physiological tests and molecular techniques related to the 16S ribosomal
      ribonucleic acid. The isolated strain produced amylase, which was purified. This
      amylase had an apparent molecular mass of 30 kDa as estimated by sodium dodecyl
      sulfate (SDS) polyacrylamide gel electrophoresis. Amylase US147 showed K (m) and
      V (max) values of 0.7 mg/ml and 2.2 U/ml, respectively, with starch as the
      substrate. The enzyme was active in acid and basic pH and had a maximal activity
      on starch at pH 9 and 70 degrees C. The enzyme was stable at pH 9 for 72 h and
      retained half of its activity after incubation at 70 degrees C for 150 min. A
      partially inhibition (15%, 25%, 23%, 20%, and 22%) was obtained with 1 mM SDS, 1
      mM NaBO(3), 1 mM H(2)O(2,) 1 mM Zn(+2), and 5 mM ethylenediamine tetraacetic acid
      (EDTA), respectively. The amylase recovered its original activity by the addition
      of 10 mM Ca (2+) to the 5 mM EDTA. These properties indicated a possible use of
      this amylase in starch saccharification, in detergent, and in other industrial
      applications.

PMID- 18626596
TI  - Optical methods.
AB  - Molecular imaging requires the highest possible signal-to-noise ratios (SNRs) at
      the target of interest. In order to maximize the SNR for optical imaging
      techniques, various strategies have been developed to design fluorescent probes
      that can be activated, for example, by proteolytic degradation. Generally
      speaking, these probes are quenched in their native state-e.g., by fluorescence
      resonance energy transfer (FRET)-and dequenched after cleavage or hybridization,
      which is associated with a strong fluorescence signal increase. Different
      strategies of fluorescence signal amplification ranging from large and small
      protease-sensing molecules to oligonucleotide-sensing and nanoparticle-based
      probes are presented in this chapter.

PMID- 18626597
TI  - PET and SPECT.
AB  - Assessment of gene function following the completion of human genome sequencing
      may be done using radionuclide imaging procedures. These procedures are needed
      for the evaluation of genetically manipulated animals or newly designed
      biomolecules which require a thorough understanding of physiology, biochemistry
      and pharmacology. The experimental approaches will involve many new technologies,
      including in-vivo imaging with SPECT and PET. Nuclear medicine procedures may be
      applied for the determination of gene function and regulation using established
      and new tracers or using in-vivo reporter genes, such as genes encoding enzymes,
      receptors, antigens or transporters. Visualization of in-vivo reporter gene
      expression can be done using radiolabeled substrates, antibodies or ligands.
      Combinations of specific promoters and in-vivo reporter genes may deliver
      information about the regulation of the corresponding genes. Furthermore, protein
      protein interactions and the activation of signal transduction pathways may be
      visualized noninvasively. The role of radiolabeled antisense molecules for the
      analysis of mRNA content has to be investigated. However, possible applications
      are therapeutic interventions using triplex oligonucleotides with therapeutic
      isotopes, which can be brought near to specific DNA sequences to induce DNA
      strand breaks at selected loci. After the identification of new genes, functional
      information is required to investigate the role of these genes in living
      organisms. This can be done by analysis of gene expression, protein-protein
      interaction or the biodistribution of new molecules and may result in new
      diagnostic and therapeutic procedures, which include visualization of and
      interference with gene transcription, and the development of new biomolecules to
      be used for diagnosis and treatment. Furthermore, the characterization of tumor
      cell-specific properties allows the design of new treatment modalities, such as
      gene therapy, which circumvent resistance mechanisms towards conventional
      chemotherapeutic drugs.

PMID- 18626598
TI  - Environment-sensitive and enzyme-sensitive MR contrast agents.
AB  - The majority of approved MR contrast agents belong to the class of paramagnetic
      chelates. These small molecules are uniquely suited to respond to changes in the
      microenvironment in vivo. These contrast agents can also function as substrates
      for several classes of enzymes. In both cases, the chelates can be designed in a
      way that the relaxivity - i.e., the ability of chelated paramagnetic metal
      cations to shorten the relaxation times of water - is directly affected by
      changes in the microenvironment. This chapter summarizes a variety of MR contrast
      agent designs that enable "sensing" of metal cations, pH and enzymatic activity.

PMID- 18626599
TI  - Peptides, multimers and polymers.
AB  - Due to their favorable properties and pharmacokinetics, peptides are often
      regarded as "agents of choice" for imaging and radiotherapy. Chemical strategies
      have been developed that allow their site specific labeling with various
      radionuclides for PET and SPECT, without compromising their biological integrity.
      Together with the overexpression of a wide range of peptide receptors and binding
      sites on tumor cells or matrix components, this class of compounds offers
      multiple imaging applications. Furthermore, radiolabeled peptides have great
      potential as carrier molecules for site-specific delivery of other signalling
      units, such as fluorescent moieties, cyctotoxic compounds or metals for magnetic
      resonance imaging. In addition, great efforts have been made to exploit the
      favorable characteristics of peptides for the development of larger constructs,
      such as multimeric ligands, polymer-peptide conjugates and "peptide-coated"
      liposomes and nanoparticles. Some peptides have already entered clinical routine
      application; some are currently being evaluated in clinical studies. However, a
      variety of peptides is still "waiting" to enter the imaging arena. This chapter
      presents a brief overview of the highly active field of peptide
      radiopharmaceuticals and the future potential of multimeric and polymeric peptide
      constructs.

PMID- 18626600
TI  - Small molecule receptors as imaging targets.
AB  - The aberrant expression and function of certain receptors in tumours and other
      diseased tissues make them preferable targets for molecular imaging. PET and
      SPECT radionuclides can be used to label specific ligands with high affinity for
      the target receptors. The functional information obtained from imaging these
      receptors can be used to better understand the systems under investigation and
      for diagnostic and therapeutic applications. This review discusses some of the
      aspects of receptor imaging with small molecule tracers by PET and SPECT and
      reviews some of the tracers for the receptor imaging of tumours and brain, heart
      and lung disorders.

PMID- 18626601
TI  - Enzymes/transporters.
AB  - Tracers that specifically target tumours are highly warranted for diagnosis and
      to monitor cancer chemotherapy response. However, as cancer cells arise from
      normal cells they do not substantially differ from the normal cells and therefore
      tumour specific targets are rare. Fortunately, the process of malignant
      transformation is associated with the up- or down-regulation of enzymes and
      transporters that play a crucial role in tumour growth. Consequently diagnostic
      imaging procedures have attained their major success with tracers that target
      enzymes and transporters that are over-expressed in tumours. The glucose
      transporters, the multi drug resistance transporters (MDRPs), several kinases and
      the family of cathepsins are prominent examples for enzymes and receptors that
      can be targeted for molecular imaging.

PMID- 18626602
TI  - Phage peptide display.
AB  - Molecular imaging is at the forefront in the advancement of in-vivo diagnosis and
      monitoring of cancer. New peptide-based molecular probes to facilitate cancer
      detection are rapidly evolving. Peptide-based molecular probes that target
      apoptosis, angiogenesis, cell signaling and cell adhesion events are in place.
      Bacteriophage (phage) display technology, a molecular genetic approach to ligand
      discovery, is commonly employed to identify peptides as tumor-targeting
      molecules. The peptide itself may perhaps have functional properties that
      diminish tumor growth or metastasis. More often, a selected peptide is chemically
      synthesized, coupled to a radiotracer or fluorescent probe, and utilized in the
      development of new noninvasive molecular imaging probes. A myriad of peptides
      that bind cancer cells and cancer-associated antigens have been reported from
      phage library selections. Phage selections have also been performed in live
      animals to obtain peptides with optimal stability and targeting properties in
      vivo. To this point, few in-vitro, in-situ, or in-vivo selected peptides have
      shown success in the molecular imaging of cancer, the notable exception being
      vascular targeting peptides identified via in-vivo selections. The success of
      vasculature targeting peptides, such as those with an RGD motif that bind
      alpha(v)beta(3)integrin, may be due to the abundance and expression patterns of
      integrins in tumors and supporting vasculature. The discovery of molecular probes
      that bind tumor-specific antigens has lagged considerably. One promising means to
      expedite discovery is through the implementation of selected phage themselves as
      tumor-imaging agents in animals.

PMID- 18626604
TI  - The use of ultrasound in transfection and transgene expression.
AB  - The interaction of ultrasound with tissue leads to radiation pressure, heat
      generation, and cavitation. These phenomena have been utilised for local gene
      delivery, transfection and control of expression. Specially designed nanocarriers
      or adapted ultrasound contrast agents can further enhance local delivery by: (1)
      increased permeability of cell membranes; (2) local release of genes. Biological
      carriers may also be used for local gene delivery. Stem cells and immune cells
      appear especially promising because of their homing capabilities to lesion sites.
      Imaging methods can be employed for pharmacodistribution and pharmacokinetics.
      MRI contrast agents can serve as non-invasive reporters on gene distribution when
      co-delivered with the gene. They can be used to label nanocarriers and cellular
      transport systems in gene therapy strategies such as those based on stem cells.
      Finally, ultrasound heating together with the use of a temperature sensitive
      promoter allows a local, physical, spatio-temporal control of transgene
      expression, in particular when combined with MRI temperature mapping for
      monitoring and even controlling ultrasound heating.

PMID- 18626603
TI  - Molecular imaging: reporter gene imaging.
AB  - Non-invasive in-vivo molecular genetic imaging developed over the past decade and
      predominantly utilises radiotracer (PET, gamma camera, autoradiography), magnetic
      resonance and optical imaging technology. Molecular genetic imaging has its roots
      in both molecular biology and cell biology. The convergence of these disciplines
      and imaging modalities has provided the opportunity to address new research
      questions, including oncogenesis, tumour maintenance and progression, as well as
      responses to molecular-targeted therapy. Three different imaging strategies are
      described: (1) "bio-marker" or "surrogate" imaging; (2) "direct" imaging of
      specific molecules and pathway activity; (3) "indirect" reporter gene imaging.
      Examples of each imaging strategy are presented and discussed. Several
      applications of PET- and optical-based reporter imaging are demonstrated,
      including signal transduction pathway monitoring, oncogenesis in genetic mouse
      models, endogenous molecular genetic/biological processes and the response to
      therapy in animal models of human disease. Molecular imaging studies will
      compliment established ex-vivo molecular-biological assays that require tissue
      sampling by providing a spatial and a temporal dimension to our understanding of
      disease development and progression, as well as response to treatment. Although
      molecular imaging studies are currently being performed primarily in experimental
      animals, we optimistically expect they will be translated to human subjects with
      cancer and other diseases in the near future.

PMID- 18626605
TI  - Magnetic resonance of mouse models of cardiac disease.
AB  - In recent years magnetic resonance imaging (MRI) has become the noninvasive
      standard for the quantitative evaluation of cardiac function, masses, and infarct
      size. Wall motion analysis is used to display myocardial dysfunction and
      microcirculatory deficits can be displayed by perfusion imaging and
      quantification of the myocardial regional blood volume. Magnetic resonance
      spectroscopy (MRS) also provides quantitative information on cardiac energetics
      and, in combination with MRI, insights into cardiac structure and function. The
      use of both techniques permits complementary data collection within the same
      experimental setup.Nevertheless, it should be mentioned that MR does not directly
      visualize genes or gene product expression but morphological or bioenergetical
      outcomes of gene expression instead. In conclusion, cardiac MR is a valuable tool
      applicable to mouse phenotyping and, also, can be applied to assess the effects
      of therapeutic agents. Thus, MR of mouse models of cardiac disease has great
      potential to substantially contribute to the understanding of the underlying
      pathomechanisms and can help to evaluate new therapy options.

PMID- 18626606
TI  - Translational imaging: imaging of apoptosis.
AB  - Since its original description in 1972, apoptosis or programmed cell death has
      been recognized as the major pathway by which the body precisely regulates the
      number and type of its cells as part of normal embryogenesis, development, and
      homeostasis. Later it was found that apoptosis was also involved in the
      pathogenesis of a number of human diseases, cell immunity, and the action of
      cytotoxotic drugs and radiation therapy in cancer treatment. As such, the imaging
      of apoptosis with noninvasive techniques such as with radiotracers, including
      annexin V and lipid proton magnetic resonance spectroscopy, may have a wide range
      of clinical utility in both the diagnosis and monitoring therapy of a wide range
      of human disorders. In this chapter we review the basic biochemical and
      morphologic features of apoptosis and the methods developed thus far to image
      this complex process in humans.

PMID- 18626607
TI  - Molecular imaging of PET reporter gene expression.
AB  - Multimodality molecular imaging continues to rapidly expand and is impacting many
      areas of biomedical research as well as patient management. Reporter-gene assays
      have emerged as a very general strategy for indirectly monitoring various
      intracellular events. Furthermore, reporter genes are being used to monitor
      gene/cell therapies, including the location(s), time variation, and magnitude of
      gene expression. This chapter reviews reporter gene technology and its major pre
      clinical and clinical applications to date. The future appears quite promising
      for the continued expansion of the use of reporter genes in many evolving
      biomedically related arenas.

PMID- 18626608
TI  - Noninvasive cell tracking.
AB  - Cell-based therapies may gain future importance in defeating different kinds of
      diseases, including cancer, immunological disorders, neurodegenerative diseases,
      cardiac infarction and stroke. In this context, the noninvasive localization of
      the transplanted cells and the monitoring of their migration can facilitate basic
      research on the underlying mechanism and improve clinical translation. In this
      chapter, different ways to label and track cells in vivo are described. The
      oldest and only clinically established method is leukocyte scintigraphy, which
      enables a (semi)quantitative assessment of cell assemblies and, thus, the
      localization of inflammation foci. Noninvasive imaging of fewer or even single
      cells succeeds with MRI after labeling of the cells with (ultrasmall)
      superparamagentic iron oxide particles (SPIO and USPIO). However, in order to
      gain an acceptable signal-to-noise ratio, at a sufficiently high spatial
      resolution of the MR sequence to visualize a small amount of cells, experimental
      MR scanners working at high magnetic fields are usually required. Nevertheless,
      feasibility of clinical translation has been achieved by showing the localization
      of USPIO-labeled dendritic cells in cervical lymph nodes of patients by clinical
      MRI.Cell-tracking approaches using optical methods are important for preclinical
      research. Here, cells are labeled either with fluorescent dyes or quantum dots,
      or transfected with plasmids coding for fluorescent proteins such as green
      fluorescent protein (GFP) or red fluorescent protein (RFP). The advantage of the
      latter approach is that the label does not get lost during cell division and,
      thus, makes imaging of proliferating transplanted cells (e.g., tumor cells)
      possible. In summary, there are several promising options for noninvasive cell
      tracking, which have different strengths and limitations that should be
      considered when planning cell-tracking experiments.

PMID- 18626609
TI  - Noninvasive tracer techniques to characterize angiogenesis.
AB  - Great efforts are being made to develop antiangiogenesis drugs for treatment of
      cancer as well as other diseases. Some of the compounds are already in clinical
      trials. Imaging techniques allowing noninvasive monitoring of corresponding
      molecular processes can provide helpful information for planning and controlling
      corresponding therapeutic approaches but will also be of interest for basic
      science. Current nuclear medicine techniques focus on the development of tracer
      targeting the vascular endothelial growth factor (VEGF) system, matrix
      metalloproteinases (MMP), the ED-B domain of a fibronectin isoform, and the
      integrin alphavbeta3. In this chapter, the recent tracer developments as well as
      the preclinical and the clinical evaluations are summarized and the potential of
      the different approaches to characterize angiogenesis are discussed.

PMID- 18626610
TI  - Molecular imaging-guided gene therapy of gliomas.
AB  - Gene therapy of patients with glioblastoma using viral and non-viral vectors,
      which are applied by direct injection or convection-enhanced delivery (CED),
      appear to be satisfactorily safe. Up to date, only single patients show a
      significant therapeutic benefit as deduced from single long-term survivors. Non
      invasive imaging by PET for the identification of viable target tissue and for
      assessment of transduction efficiency shall help to identify patients which might
      benefit from gene therapy, while non-invasive follow-up on treatment responses
      allows early and dynamic adaptations of treatment options. Therefore, molecular
      imaging has a critical impact on the development of standardised gene therapy
      protocols and on efficient and safe vector applications in humans.

PMID- 18626612
TI  - [Cutaneous leishmaniasis].
AB  - Leishmaniasis includes a spectrum of different diseases that differ in their
      clinical appearance and severity and influence the patient's health to varying
      degrees. All the diseases are caused by parasites of the genus Leishmania. The
      simplest and most widely used classifications use the clinical features and the
      geographic distribution. Cutaneous leishmaniasis can be divided into localized,
      diffuse, recurrent or post-kala-azar. Using the geographic distribution
      leishmaniasis of the Old World, is found in Africa, Asia, Middle East,
      Mediterranean basin and India. Both, cutaneous and visceral leishmaniasis, may
      develop. In contrast, New World leishmaniasis is caused by leishmania found in
      Central and South America and cause may cutaneous, mucocutaneous and visceral
      findings.

PMID- 18626613
TI  - [Vacuum-therapy of chronic wounds in dermatologic departments].
AB  - Although the positive effects of negative pressure-therapy in wound-healing has
      been well known for several decades, the first paper on the now widely used
      vacuum systems was published ten years ago. Since then vacuum-therapy has been
      widely used in patients with"hard-to-heal" wounds, including dermatologic
      patients. Although there is still a lack of relevant comparative prospective
      controlled clinical trials, vacuum-therapy seems to accelerate the healing
      process in chronic wounds in both the granulation and epithelialization phases.
      Therefore, following debridement, vacuum-therapy can be considered as the therapy
      of choice for many patients with chronic wounds.

PMID- 18626614
TI  - [Tungiasis and myiasis].
AB  - Tungiasis (sand flea disease) and myiasis are ectoparasitoses, in which the
      infectious agent resides temporarily in the skin (myiasis) or dies and is
      eventually eliminated (tungiasis). Both diseases are zoonoses. Whereas in myiasis
      humans are only an accidental host, in tungiasis the prevalence in humans is
      similar to that of their domestic animals. In travellers returning from the
      tropics tungiasis and myiasis are not rare, however they are frequently
      misdiagnosed. The diagnosis of both infestations is made clinically, and
      laboratory investigations are not helpful. In tungiasis the clinical picture
      depends on the stage of the disease. A heavy local inflammation and bacterial
      superinfection are frequent. Therapy consists in the complete elimination of the
      parasite. The repellent Zanzarin effectively protects against sand fleas.

PMID- 18626615
TI  - [Cutaneous larva migrans].
AB  - As a result of the rise of mass tourism with increasingly cheap and exotic
      destinations, tropical diseases are becoming an increasingly important part of
      dermatology. Infection with cutaneous larva migrans is one of the most common
      "souvenirs" from the tropics. The disease is caused by the nematode infection
      with dog or cat hookworm parasites (Ancylostoma braziliense or A. caninum). The
      characteristic manifestation is a gyrated, serpiginous and in some cases
      vesicular erythema, which appears after penetration of the epidermis by the
      parasite and the subsequent intraepidermal migration of the larva. This is often
      accompanied by intense pruritus in the affected skin. The infection is usually
      found in those areas of the foot, calf or buttocks exposed by walking or sitting
      on sand. Although subjectively very unpleasant, the disease is self-limiting and
      resolves after several weeks; it is treated locally in most cases (e.g. using
      cryotherapy). The prognosis of the disease is excellent, but a prolonged course
      or complications have been observed, e.g. due to superinfection.

PMID- 18626616
TI  - [Arthropod bite reactions and pyodermias].
AB  - Tourists in the tropics often develop reactions to bites or stings of mosquitoes,
      fleas, mites, ants, bedbugs, beetles, larva, millipedes, spiders and scorpions.
      In addition, they may have fresh or salt water exposure to sponges, corals,
      jellyfish and sea urchins with resultant injury and inflammation. Bacterial skin
      infections (pyodermias) can follow bites or stings as well as mechanical trauma.
      The most common bacteria involved in skin infections are staphylococci and
      streptococci. For tourists, bacterial infections are often complicating a
      pruritic bite reaction and scratching. It is important to know the cause of the
      bite reaction and pyoderma in order to take appropriate therapeutic measures.

PMID- 18626617
TI  - Tissue-specific contaminant accumulation and associated effects on hepatic serum
      analytes and cytochrome P450 enzyme activities in hooded seals (Cystophora
      cristata) from the Gulf of St. Lawrence.
AB  - The current study aims to assess contaminant levels and tissue burdens in hooded
      seal (Cystophora cristata) blubber, liver, and blood in association with
      cytochrome P450 (CYP) enzymes (CYP1A and -3A) and serum analytes (hepatic enzymes
      like alanine aminotransferase [ALT], aspartate aminotransferase, alkaline
      phosphatase [AP], and gamma-glutamyltransferase [GGT], serum proteins, and
      creatine kinase). Contaminant accumulation levels and patterns of polychlorinated
      biphenyls, chlorinated pesticides, and polybrominated diphenyl ethers (PBDEs)
      differed between tissues and seal groups, with the highest levels in liver. Pups
      showed higher liver contaminant levels, especially for PBDEs, than adults. These
      high levels might be associated with the ingestion of large amounts of
      contaminated milk and subsequent accumulation in the liver. Adult males and
      females mainly differed in PBDE levels, which were higher in females, possibly
      due to a sex-specific diet. The association between blubber contaminant burdens
      and the diagnostic enzymes ALT, GGT, and AP, and serum albumin, was inconclusive.
      In contrast, several CYP isoenzymes showed a clear positive relationship with the
      overall blubber contaminant burden, indicating enzyme induction following
      exposure to polyhalogenated hydrocarbons. Therefore, liver CYP isoenzymes may
      serve as a sensitive biomarker for long-term exposure to polyhalogenated
      hydrocarbons.

PMID- 18626618
TI  - [Treatment of intraventricular hemorrhage and hydrocephalus].
AB  - Most cases of intraventricular hemorrhage (IVH) occur secondary to spontaneous
      intracerebral or subarachnoid hemorrhage. The main concern is development of
      hydrocephalus, which is related to a poor prognosis. Over the last years, several
      treatment options for IVH have been introduced, but prospective data regarding
      the efficacy of those therapies (external ventricular drainage, intraventricular
      fibrinolysis, lumbar drainage, endoscopic hematoma evacuation) do not yet exist.
      This review focuses on combined therapy using an external ventricular drain and
      intraventricular fibrinolysis with r-TPA for IVH-associated initial occlusive
      hydrocephalus. Moreover, a continuing treatment strategy for persistent
      malresorptive communicating hydrocephalus using lumbar drainage is described.

PMID- 18626619
TI  - [Ins and outs of neurologic therapy for chronic pain].
AB  - Although chronic pain is common, especially in elderly patients, its treatment
      often remains inadequate. One of many reasons for this is that insufficient
      therapy of acute pain carries the risk of making the pain chronic. Sooner or
      later most patients suffering from chronic pain will consult a neurologist.
      However, in most neurological departments, pain treatment is neither one of the
      common medical activities nor a subject in medical education. In Germany, only
      specialised centres have associated pain outpatient clinics, so it is almost
      impossible for neurologist trainees to improve their knowledge in pain treatment.
      This review provides a synopsis of procedures regarding chronic pain treatments,
      with particular focus on the most frequent pain disorders. The treatment
      recommendations follow the current guidelines of the German Society of Neurology.

PMID- 18626620
TI  - [Proportion of tau protein to phosphorylated tau protein CSF levels in
      differential diagnosis of dementia].
AB  - BACKGROUND: The diagnosis of Creutzfeldt-Jakob disease (CJD) is based on typical
      clinical features and can be supported by detection of 14-3-3 protein in the CSF.
      The present study suggests the importance of investigating this ratio of total
      tau protein to phosphorylated tau protein in differentiating CJD from other
      dementias. Thirty-one patients with Alzheimer's disease (AD) or frontotemporal
      dementia and four with definitive diagnoses of CJD were included in the study.
      METHODS AND MATERIAL: Results from baseline investigations were compared with
      those from an age-matched cognitively controlled group with Bell's palsy. Tau
      protein, phosphorylated tau protein, and beta amyloid were analyzed using a
      commercially available enzyme-linked immunosorbent assay; 14-3-3 protein was
      assessed by Western blotting. RESULTS AND CONCLUSION: A distinctly high
      proportion of total tau protein to phosphorylated tau protein in CSF was found in
      all patients diagnosed with CJD, even in those with negative 14-3-3 protein blot
      results. In contrast, marker analysis in patients with Alzheimer's dementia
      revealed the highest CSF ratio of beta amyloid to phosphorylated tau protein
      levels. These proteins are important diagnostic biomarkers for CJD, especially in
      patients with negative 14-3-3 protein findings.

PMID- 18626621
TI  - [Improper cooperation contract between a hospital and a physician].
AB  - The term interdisciplinary care is frequently used to indicate the often
      criticized division between inpatient and outpatient treatment. Interdisciplinary
      care in the actual sense in the form of integrated care necessarily requires the
      involvement of health insurance providers as the contractual partner.

PMID- 18626622
TI  - [Liability for outpatient examination and inadequately informing the patient
      during subsequent inpatient treatment].

PMID- 18626623
TI  - Genetic linkage mapping of the soybean aphid resistance gene in PI 243540.
AB  - The soybean aphid (Aphis glycines Matsumura) is a pest of soybean [Glycine max
      (L.) Merr.] in many soybean growing countries of the world, mainly in Asia and
      North America. A single dominant gene in PI 243540 confers resistance to the
      soybean aphid. The objectives of this study were to identify simple sequence
      repeat (SSR) markers closely linked to the gene in PI 243540 and to position the
      gene on the consensus soybean genetic map. One hundred eighty-four F2 plants and
      their F2:3 families from a cross between the susceptible cultivar Wyandot and PI
      243540, and the two parental lines were screened with the Ohio biotype of soybean
      aphid using greenhouse choice tests. A SSR marker from each 10-cM section of the
      consensus soybean map was selected for bulked segregant analysis (BSA) to
      identify the tentative genomic location of the gene. The BSA technique was useful
      to localize the gene to a genomic region in soybean linkage group (LG) F. The
      entire F2 population was then screened with polymorphic SSR markers from this
      genomic region and a linkage map with nine SSR markers flanking the gene was
      constructed. The aphid resistance gene was positioned in the interval between SSR
      markers Satt334 and Sct_033 on LG F. These SSR markers will be useful for marker
      assisted selection of this gene. The aphid resistance gene from PI 243540 mapped
      to a different linkage group than the only named soybean aphid resistance gene,
      Rag1, from 'Dowling'. Also, the responses of the two known biotypes of the
      soybean aphid to the gene from PI 243540 and Rag1 were different. Thus, the aphid
      resistance gene from PI 243540 was determined to be a new and independent gene
      that has been named Rag2.

PMID- 18626624
TI  - Development of microsatellite markers specific for the short arm of rye (Secale
      cereale L.) chromosome 1.
AB  - We developed 74 microsatellite marker primer pairs yielding 76 polymorphic loci,
      specific for the short arm of rye chromosome 1R (1RS) in wheat background. Four
      libraries enriched for microsatellite motifs AG, AAG, AC and AAC were constructed
      from DNA of flow-sorted 1RS chromosomes and 1,290 clones were sequenced.
      Additionally, 2,778 BAC-end-sequences from a 1RS specific BAC library were used
      for microsatellite screening and marker development. From 724 designed primer
      pairs, 119 produced 1RS specific bands and 74 of them showed polymorphism in a
      set of ten rye genotypes. We show that this high attrition rate was due to the
      highly repetitive nature of the rye genome consisting of a large number of
      transposable elements. We mapped the 76 polymorphic loci physically into three
      regions (bins) on 1RS; 29, 30 and 17 loci were assigned to the distal,
      intercalary and proximal regions of the 1RS arm, respectively. The average
      polymorphism information content increases with distance from the centromere,
      which could be due to an increased recombination rate along the chromosome arm
      toward's the telomere. Additionally, we demonstrate, using the data of the whole
      rice genome, that the intra-genomic length variation of microsatellites
      correlates (r = 0.87) with microsatellite polymorphism. Based on these results we
      suggest that an analysis of the microsatellite length variation is conducted for
      each species prior to microsatellite development, provided that sufficient
      sequence information is available. This will allow to selectively design
      microsatellite markers for motifs likely to yield a high level of polymorphism.

PMID- 18626625
TI  - Ethnic differences in retinal microvascular structure.
AB  - AIMS/HYPOTHESIS: People of African origin have increased risk of stroke and
      retinal microvascular disease compared with populations of European origin. We
      compared quantitative measures of retinal microvasculature in British white
      Europeans and African Caribbeans. METHODS: Population-based study of 215 (45%
      male) British African-Caribbean migrants and 323 (48% male) white Europeans aged
      40-69 years. Digitised retinal images were analysed using a validated semi
      automated system. RESULTS: Arteriolar optimality deviation, an indicator of
      endothelial dysfunction, was greater in African Caribbeans (age- and sex-adjusted
      means [95% CIs]: 0.06 [0.05-0.06] vs 0.04 [0.04-0.05], p = 0.004); this was
      unexplained by conventional risk factors. Arteriolar diameters were narrower in
      African Caribbeans (age- and sex-adjusted means [95% CIs]: 18.4 [18.1-18.6] vs
      17.9 [17.6-18.2], p = 0.011). These ethnic differences in diameters were
      attenuated on adjustment for systolic BP (SBP) (adjusted means: 18.2 vs 18.1, p =
      0.31). However, there was a significant interaction (p = 0.011) between diabetes
      and SBP, such that SBP was strongly associated with arteriolar diameter in people
      without diabetes, but not in those with diabetes (adjusted beta-coefficients for
      SBP: Europeans: -0.42, p = 0.002 vs 0.17, p = 0.69, African Caribbeans: -0.35, p
      = 0.023 vs 0.01, p = 0.96). Other measures of retinal vasculature did not differ
      by ethnicity. CONCLUSIONS/INTERPRETATION: British African Caribbeans appear to
      have poorer retinal arteriolar endothelial function than white Europeans. Higher
      BPs explained the narrower arterioles in African Caribbeans; however, patterns of
      association between arteriolar narrowing and BP suggest the possibility that
      cerebral autoregulation and/or remodelling might be adversely affected by
      diabetes in both ethnic groups.

PMID- 18626626
TI  - Alcohol consumption and risk of microvascular complications in type 1 diabetes
      patients: the EURODIAB Prospective Complications Study.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate the association between
      alcohol consumption and risk of microvascular complications (retinopathy,
      neuropathy, nephropathy) in type 1 diabetes mellitus patients in the EURODIAB
      Prospective Complications Study. METHODS: The EURODIAB Prospective Complications
      Study is a follow-up study including 3,250 type 1 diabetes mellitus patients from
      16 different European countries. We investigated the cross-sectional association
      between moderate alcohol consumption and risk of retinopathy, neuropathy and
      nephropathy among 1,857 of these patients. RESULTS: We documented 304 cases of
      proliferative retinopathy, 660 cases of neuropathy and 157 cases of nephropathy
      (macroalbuminuria). Alcohol consumption was associated with risk of proliferative
      retinopathy, neuropathy and macroalbuminuria in a U-shaped fashion. Moderate
      consumers (30-70 g alcohol per week) had a lower risk of microvascular
      complications with odds ratios of 0.60 (95% CI 0.37-0.99) for proliferative
      retinopathy, 0.61 (0.41-0.91) for neuropathy and 0.36 (0.18-0.71) for
      macroalbuminuria in multivariate-adjusted models. These results were similar when
      excluding patients who had been advised to drink less alcohol because of their
      health. The relation was most pronounced for alcohol consumption from wine.
      Drinking frequency was significantly, inversely associated with risk of
      neuropathy, but a similar trend was visible for proliferative retinopathy and
      macroalbuminuria. Alcohol consumption was not associated with occurrence of
      ketoacidosis or hypoglycaemic attacks. CONCLUSIONS/INTERPRETATION: Consistent
      with its effects on macrovascular complications, moderate alcohol consumption is
      associated with a lower risk of all microvascular complications among type 1
      diabetes patients.

PMID- 18626627
TI  - Natriuretic peptides in acute pulmonary embolism: a systematic review.
AB  - BACKGROUND: Patients with pulmonary embolism (PE) have a high risk of death, and
      it is important to recognize factors associated with higher mortality. Recently,
      several biomarkers have been studied for risk stratification in patients with PE.
      OBJECTIVES: Evaluate the available evidence on (a) the accuracy of brain
      natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT
      proBNP) for the diagnosis of right ventricular dysfunction and (b) their value as
      a prognostic factor of all-cause in-hospital or short-term mortality in patients
      with PE. DATA SOURCES: MEDLINE, Embase, and citation review of relevant primary
      and review articles. SELECTION CRITERIA: We selected studies evaluating the
      accuracy of BNP or NT-proBNP for the diagnosis of right ventricular dysfunction.
      We also selected studies that reported data on BNP or NT-proBNP as a predictor of
      short-term mortality in patients with PE. RESULTS: Sixteen studies met our
      inclusion criteria. The pooled diagnostic odds ratio for the diagnosis of right
      ventricular dysfunction in pulmonary embolism was 39.45 (95% CI; 15.54-100.12)
      and 24.73 (95% CI 2.02-302.37) for BNP and NT-proBNP, respectively. The pooled
      odds ratio for all-cause in-hospital or short-term mortality was 6 (95% CI 1.31
      27.43; p: 0.021) and 16.12 (95% CI 3.1-83.68; p: 0.001) for BNP (cutoff: 100
      pg/ml) and NT-proBNP (cutoff: 600 ng/L), respectively. CONCLUSION: The results of
      this meta-analysis indicate that BNP and NT-proBNP are associated with the
      diagnosis of right ventricular dysfunction (RVD) in patients with an acute PE and
      are significant predictors of all-cause in-hospital or short-term mortality in
      these patients.

PMID- 18626628
TI  - Immunonutrition in critically ill patients: a systematic review and analysis of
      the literature.
AB  - BACKGROUND: The role of immuno-modulating diets (IMDs) in critically ill patients
      is controversial. OBJECTIVE: The goal of this meta-analysis was to determine the
      impact of IMD's on hospital mortality, nosocomial infections and length of stay
      (LOS) in critically ill patients. Outcome was stratified according to type of IMD
      and patient setting. DATA SOURCES: MEDLINE, Embase, Cochrane Register of
      Controlled Trials. STUDY SELECTION: RCT's that compared the outcome of critically
      ill patients randomized to an IMD or a control diet. DATA SYNTHESIS: Twenty-four
      studies (with a total of 3013 patients) were included in the meta-analysis; 12
      studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the
      studies used formulas supplemented with arginine, two with arginine and
      glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and
      FO, six with glutamine alone and three studies used a formula supplemented with
      FO alone. Overall IMD's had no effect on mortality or LOS, but reduced the number
      of infections (OR 0.63; 95% CI 0.47-0.86, P = 0.004, I(2) = 49%). Mortality,
      infections and LOS were significantly lower only in the ICU patients receiving
      the FO IMD (OR 0.42, 95% CI 0.26-0.68; OR 0.45, 95% CI 0.25-0.79 and WMD -6.28
      days, 95% CI -9.92 to -2.64, respectively). CONCLUSIONS: An IMD supplemented with
      FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMDs
      supplemented with arginine with/without additional glutamine or FO do not appear
      to offer an advantage over standard enteral formulas in ICU, trauma and burn
      patients.

PMID- 18626629
TI  - Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits.
AB  - OBJECTIVE: Recent evidence demonstrated that hypercapnic acidosis due to lung
      protective strategy was not only permissive but also even therapeutic for injured
      lung. Since the effects of hypercapnic acidosis on extra-pulmonary organs remain
      to be clarified, we tested the hypothesis that hypercapnic acidosis protects gut
      mucosal barrier function by modulating inflammation in a rabbit model of
      endotoxemia. DESIGN: Prospective randomized animal study. SETTING: University
      research laboratory. SUBJECTS: Male New Zealand white rabbits. INTERVENTIONS:
      Thirty-two animals were randomly allocated into two groups: normocapnia (n = 17)
      and hypercapnia (n = 15). The latter group received F(I)CO(2) 5% under mechanical
      ventilation to achieve hypercapnia throughout the study periods, whereas the
      former with F(I)CO(2) 0%. MEASUREMENTS AND RESULTS: Arterial blood gas,
      intramucosal pH (pHi) and portal blood flow were assessed at baseline, 2-h and 4
      h infusion of lipopolysaccharide. At 4 h, ileal myeloperoxidase (MPO) activity
      and intestinal permeability were measured. The animals in the hypercapnia group
      showed apparent hypercapnic acidosis and progressive intramucosal acidosis at 4
      h, accompanied by significantly lower intestinal permeability versus normocapnia
      group. Ileal MPO activity was comparable between the study groups. CONCLUSIONS:
      Hypercapnic acidosis attenuates endotoxin-induced gut barrier dysfunction
      possibly through neutrophil-independent mechanisms.

PMID- 18626631
TI  - Molecularly imprinted polymers: modulating molecular recognition by a thermal
      phase transition in the binding framework.
AB  - The concept used to realize the modulation of molecular recognition in a
      molecularly imprinted polymer is presented. Creating a thermal phase transition
      within the binding framework, the imprinted material was prepared using Boc
      phenylalanine as the template and pNIPAM as the sensitive unit. The results
      indicate that such a transition causes a clear modulation in the recognition
      behavior of the prepared polymer which depends on the operation temperature. At a
      relatively low temperature, the prepared polymer acts like a traditionally
      imprinted one, showing a highly specific recognition for the imprint species.
      However, the prepared polymer does not present any notable resolution at 40
      degrees C. This recognition behavior is comparable to a process that can be
      switched on and off, thus making modulated recognition feasible.

PMID- 18626632
TI  - Detection of electrophoretically separated cytochromes P450 by element-labelled
      monoclonal antibodies via laser ablation inductively coupled plasma mass
      spectrometry.
AB  - Numerous structurally and enzymatically similar cytochromes P450 (CYPs) are
      involved in the metabolism of xenobiotics and are present in different amounts
      and with different enzyme profiles in human tissues and cells. Analysis of their
      adaptively regulated and individually variable patterns is a peculiar analytical
      challenge. We developed a laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS) based method for concomitant detection and
      semiquantitative determination of electrophoretically separated and blotted CYPs.
      The first results are given here for the two enzymes CYP1A1 and CYP2E1. Specific
      monoclonal antibodies directed against the enzymes were differentially labelled
      with europium via a covalently linked chelator and with iodine, respectively.
      Analysis of the modified antibodies shows that both europium and iodine are
      coupled to the heavy and the light chains of the antibodies. Also, the antibodies
      maintained their antigen-binding properties after labelling as demonstrated by LA
      ICP-MS-analysed immunoblots. The method allowed us to detect specifically and
      concomitantly both CYP enzymes in complex biological samples, i.e. microsomes of
      rat liver and minipig duodenum, which are characterized by different levels and
      proportions of the two CYP enzymes. A strong CYP1A1 signal is found in liver
      microsomes of 3-methylcholanthrene-treated rats, while it is (nearly) absent in
      liver microsomes of rats treated with isonocotinic acid hydrazide (isoniazid).
      The constitutively expressed CYP2E1 is found in microsomes of both treatment
      groups. Duodenal microsomes of minipigs orally exposed to polycyclic aromatic
      hydrocarbons show a clear CYP1A1 signal. Low levels of CYP2E1 can also be
      detected in these microsomes. The LA-ICP-MS method allows concomitant
      determination of CYPs, thereby exhibiting sensitivity similar to that of
      conventional chemoluminescence detection via peroxidase-labelled secondary
      antibodies. The latter method allows readout of a single CYP protein in a 1D
      separation. Although the results presented here are only for labelling by use of
      the elements iodine and europium, the same strategy can be applied also for other
      lanthanide elements in combination with chelating compounds, so LA-ICP-MS of
      western blots offers a new capability to be applied for highly multiplexed CYP
      determinations via labelled antibodies.

PMID- 18626634
TI  - Discontinuation of ropinirole and pramipexole in patients with Parkinson's
      disease: clinical practice versus clinical trials.
AB  - OBJECTIVE: To compare characteristics and incidence of discontinuation of
      Parkinson's disease (PD) patients starting ropinirole or pramipexole in clinical
      practice with data from randomised controlled clinical trials (RCTs). METHODS:
      Included in the retrospective clinical-practice cohort were first-time users of
      ropinirole or pramipexole diagnosed with PD before 2005. Baseline characteristics
      and incidence of discontinuation were compared between the clinical-practice
      cohort and RCTs. Treatment discontinuation was defined as more than 180 days
      between two refills of ropinirole or pramipexole. The incidence of
      discontinuation in RCTs was based on the reported rate of discontinuation for any
      cause. RESULTS: Included were 45 patients who started with ropinirole and 59
      patients who started with pramipexole. Treatment was discontinued within 3 years
      in 51% (ropinirole) and 60% (pramipexole) of the patients. Ten RCTs with
      ropinirole and 12 with pramipexole were identified. Baseline characteristics did
      not differ between the clinical-practice cohort and RCTs. RCTs reported
      discontinuation rates comparable with those at the same timepoint in the clinical
      practice until 1 year of follow-up. CONCLUSION: This study shows that the overall
      incidence of discontinuation of ropinirole and pramipexole between the patients
      in our clinical-practice cohort and patients in the RCTs was comparable for the
      short term. However for the long term, discontinuation in practice is possibly
      higher.

PMID- 18626633
TI  - Oral absorption of propiverine solution and of the immediate and extended release
      dosage forms: influence of regioselective intestinal elimination.
AB  - PURPOSE: The muscarine receptor antagonist propiverine in immediate release
      tablet form (IR) undergoes presystemic elimination mediated by CYP450 enzymes and
      intestinal efflux transporters. The aim of our study with propiverine IR and
      extended release (ER) was to determine whether propiverine disposition is dose
      linear, to compare the pharmacokinetics of propiverine in oral solution with IR
      and ER and to show how absorption rate is associated with bioavailability.
      METHODS: The pharmacokinetics of propiverine administered as intravenous
      propiverine (15 mg), 10, 15, and 30 mg propiverine IR, an oral propiverine
      solution (15 mg) and 10, 15, 30, and 45 mg propiverine ER were measured in two
      randomized, controlled, single-dose, five-period, cross-over studies, with each
      case involving a study cohort of ten healthy Caucasian subjects. RESULTS:
      Disposition of propiverine IR and ER was not dose-related. The bioavailability of
      ER was 64.5 +/- 16.1% compared to 50.3 +/- 13.4% (non-significant) after
      administration of the IR and propiverine solution (42.6 +/- 14.8%, p < 0.05). The
      mean absorption time (MAT) of ER (14.2 +/- 4.79 h) was significantly longer than
      that of the solution and IR (3.94 +/- 4.14 and 0.38 +/- 3.79 h, respectively;
      both p < 0.05). The bioavailability of propiverine was significantly correlated
      to the MAT (r = 0.521, p < 0.001). Renal excretion of the metabolite M-23 after
      propiverine ER administration (6.7 +/- 2.7%) was significantly lower than that
      after administration of the oral solution (10 +/- 2.2%) and of IR (9.8 +/- 2.7%;
      both p < 0.05). CONCLUSIONS: The bioavailability of propiverine appears to be
      dependent on the intestinal site of dissolution and, consequently, on the extent
      of presystemic intestinal elimination.

PMID- 18626635
TI  - Supracardiac type total anomalous pulmonary venous connection (TAPVC) with
      oesophageal varices.
AB  - Oesophageal varices due to total anomalous pulmonary venous connection (TAPVC) is
      very rare. Additionally, the infradiaphragmatic type is the most common type of
      oesophageal varices due to TAPVC. Paraoesophageal varices due to stenosis of the
      vertical vein of supracardiac TAPVC has not previously been reported. We describe
      paraoesophageal varices developed as a result of a connection between the left
      lower pulmonary vein and the umbilicovitelline venous system because of stenosis
      of the proximal vertical vein in supracardiac type TAPVC in a 3-day-old female
      newborn who presented with general cyanosis, tachypnoea and dyspnoea.

PMID- 18626637
TI  - Pneumoparotitis.

PMID- 18626636
TI  - Acute elbow trauma in children: role of ultrasonography.
AB  - BACKGROUND: The diagnosis of occult elbow fracture in children is often
      challenging due to equivocal or negative repeated radiographic findings.
      OBJECTIVE: To evaluate the potential diagnostic role of US in children who have
      sustained elbow trauma with an elbow joint effusion but no fracture seen on
      initial radiographs. MATERIALS AND METHODS: The study included 14 consecutive
      children (age range 5-15 years) with elbow trauma whose elbow radiographs showed
      an effusion without fracture who underwent emergency imaging (within the first 72
      h) with US and MRI. The aim of US was to demonstrate a lipohaemarthrosis in
      relation to a cortical fracture. MR imaging was used as the reference to
      differentiate fracture from bone or muscle contusions. RESULTS: In seven children
      US demonstrated a lipohaemarthrosis, and MRI demonstrated a cortical fracture in
      all these children. Conversely, among the seven children with simple
      haemarthrosis seen on US, MRI did not identify a cortical fracture in six and
      demonstrated a cortical fracture in one. CONCLUSION: Posttrauma elbow joint
      effusion in children is not always related to a cortical fracture. US appears to
      be a reliable, accurate, widely available and effective low-cost tool in these
      cases. The diagnostic clue is the detection of a lipohaemarthrosis in the
      articular recess.

PMID- 18626630
TI  - Current and prospective pharmacological targets in relation to antimigraine
      action.
AB  - Migraine is a recurrent incapacitating neurovascular disorder characterized by
      unilateral and throbbing headaches associated with photophobia, phonophobia,
      nausea, and vomiting. Current specific drugs used in the acute treatment of
      migraine interact with vascular receptors, a fact that has raised concerns about
      their cardiovascular safety. In the past, alpha-adrenoceptor agonists
      (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades
      have witnessed the advent of 5-HT(1B/1D) receptor agonists (sumatriptan and
      second-generation triptans), which have a well-established efficacy in the acute
      treatment of migraine. Moreover, current prophylactic treatments of migraine
      include 5-HT(2) receptor antagonists, Ca(2+) channel blockers, and beta
      adrenoceptor antagonists. Despite the progress in migraine research and in view
      of its complex etiology, this disease still remains underdiagnosed, and available
      therapies are underused. In this review, we have discussed pharmacological
      targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT(1
      7)), adrenergic (alpha(1), alpha(2,) and beta), calcitonin gene-related peptide
      (CGRP(1) and CGRP(2)), adenosine (A(1), A(2), and A(3)), glutamate (NMDA, AMPA,
      kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen
      and progesterone) receptors. In addition, we have considered some other targets,
      including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and
      ionotropic receptors, in relation to antimigraine therapy. Finally, the
      cardiovascular safety of current and prospective antimigraine therapies is
      touched upon.

PMID- 18626638
TI  - MHC haplotype involvement in avian resistance to an ectoparasite.
AB  - Research on immune function in evolutionary ecology has frequently focused on
      avian ectoparasites (e.g., mites and lice). However, host immunogenetics involved
      with bird resistance to ectoparasites has not been determined. The critical role
      of the major histocompatibility complex (MHC) in adaptive immunity and high
      genetic variation found within the MHC make this gene complex useful for
      exploring the immunogenetic basis for bird resistance to ectoparasites. The
      objective of this study was to determine if the avian MHC influenced resistance
      to a blood-feeding ectoparasite. Four congenic lines of chickens, differing only
      at the MHC, were comparatively infested with a cosmopolitan ectoparasite of birds
      northern fowl mite (NFM)-which is also a serious pest species of poultry. Mite
      infestations were monitored over time and mite densities (weekly and maximum)
      were compared among lines. Chickens with the MHC haplotype B21 were relatively
      resistant to NFM, compared with birds in the B15 congenic line (P < 0.02). To
      test for similar effects in an outbred genetic background, a separate experiment
      was performed with 107 commercial chickens (white leghorn, W-36 strain) infested
      with NFM. Hens were genotyped using a MHC microsatellite marker (LEI0258) and
      associations between MHC haplotype and NFM density were tested. The highest peak
      NFM populations occurred more often on hens with the B15 haplotype versus the B21
      haplotype (P = 0.012), which supported the results of the congenic study. These
      data indicate the avian MHC influences ectoparasite resistance, which is relevant
      to disease ecology and avian-ectoparasite interaction.

PMID- 18626639
TI  - Engineering of NADPH-dependent aldo-keto reductase from Penicillium citrinum by
      directed evolution to improve thermostability and enantioselectivity.
AB  - Penicillium citrinum beta-keto ester reductase (KER) can catalyze the reduction
      of methyl 4-bromo-3-oxobutyrate (BAM) to methyl (S)-4-bromo-3-hydroxybutyrate
      with high optical purity. To improve the thermostability of KER, protein
      engineering was performed using error-prone polymerase chain reaction-based
      random mutagenesis. Variants with the highest levels of thermostability contained
      the single amino acid substitutions L54Q, K245R, and N271D. The engineered L54Q
      variant of KER retained 62% of its initial activity after heat treatment at 30
      degrees C for 6 h, whereas wild-type KER showed only 15% activity. The L54Q
      substitution also conferred improved enantioselectivity by KER. An Escherichia
      coli cell biocatalyst that overproduced the L54Q mutant of KER and glucose
      dehydrogenase as a cofactor regeneration enzyme showed the highest level of BAM
      reduction in a water/butyl acetate two-phase system.

PMID- 18626640
TI  - Electricity production from xylose in fed-batch and continuous-flow microbial
      fuel cells.
AB  - A medium-scale (0.77 l) air-cathode, brush-anode microbial fuel cell (MFC)
      operated in fed-batch mode using xylose (20 mM) generated a maximum power density
      of 13 +/- 1 W/m(3) (673 +/- 43 mW/m(2)). Xylose was rapidly removed (83.5%)
      within 8 h of a 60-h cycle, with 42.1% of electrons in intermediates (8.5 +/- 0.2
      mM acetate, 5.9 +/- 0.01 mM ethanol, 4.3 +/- 0.1 mM formate, and 1.3 +/- 0.03 mM
      propionate), 9.1% captured as electricity, 16.1% in the remaining xylose, and
      32.7% lost to cell storage, biomass, and other processes. The final Coulombic
      efficiency was 50%. At a higher initial xylose concentration (54 mM), xylose was
      again rapidly removed (86.9% within 24 h of a 116-h cycle), intermediates
      increased in concentration (18.4 +/- 0.4 mM acetate, 7.8 +/- 0.4 mM ethanol and
      2.1 +/- 0.2 mM propionate), but power was lower (5.2 +/- 0.4 W/m(3)). Power was
      increased by operating the reactor in continuous flow mode at a hydraulic
      retention time of 20 h (20 +/- 1 W/m(3)), with 66 +/- 1% chemical oxygen demand
      removal. These results demonstrate that electricity generation is sustained over
      a cycle primarily by stored substrate and intermediates formed by fermentation
      and that the intermediates produced vary with xylose loading.

PMID- 18626641
TI  - Characterization of cold-active uracil-DNA glycosylase from Bacillus sp. HJ171
      and its use for contamination control in PCR.
AB  - In this study, the gene encoding Bacillus sp. HJ171 uracil-DNA glycosylase (Bsp
      HJ171 UDG) was cloned and sequenced. The Bsp HJ171 UDG gene consists of a 738-bp
      DNA sequence, which encodes for a protein that is 245-amino-acid residues in
      length. The deduced amino acid sequence of the Bsp HJ171 UDG had a high sequence
      similarity with other bacterial UDGs. The molecular mass of the protein derived
      from this amino acid sequence was 27.218 kDa. The Bsp HJ171 UDG gene was
      expressed under the control of a T7lac promoter in the pTYB1 plasmid in
      Escherichia coli BL21 (DE3). The expressed enzyme was purified in one step using
      the Intein Mediated Purification with an Affinity Chitin-binding Tag purification
      system. The optimal temperature range, pH, NaCl concentration, and KCl
      concentration of the purified enzyme was 20-25 degrees C, 8.0, 25 and 25 mM,
      respectively. The half-life of the enzyme at 40 degrees C and 50 degrees C were
      approximately 131 and 45 s, respectively. These heat-labile characteristics
      enabled Bsp HJ171 UDG to control carry-over contamination in the polymerase chain
      reaction product (PCR) without losing the PCR product.

PMID- 18626642
TI  - Acid stabilization of Bacillus licheniformis alpha amylase through introduction
      of mutations.
AB  - This paper provided further understanding of the relationships between acid
      resistance and structural features of different mutants in Bacillus licheniformis
      alpha amylase (BLA) due to the changes of two crucial positions Leu134 and
      Ser320. In order to investigate effect of the two positions on the acid
      stability, we described the detailed characterization of wild-type and the single
      mutants L134R and S320A as well as the double mutant L134R/S320A. The highest
      k(cat)/Km with pH 4.5, approximately 14 times that of wild type, was observed in
      L134R/S320A. The k(cat)/Km corresponding to L134R and S320A were at an
      intermediate values between those for wild type and L134R/S320A. In addition,
      compared with wild type, which had a rapid decline of the activity, L134R/S320A
      could maintain its activity strongly in low pH. Meanwhile, lower tolerance of
      L134R and S320A in acidic conditions than that of L134R/S320A was determined.
      Surprisingly, the acid-resistant capability of L134R/S320A was significantly
      enhanced by directed evolution. These results, combined with three-dimensional
      structure analysis, show that the electrostatic effects play a significant role
      in determining the stability of BLA at two crucial positions, 134 and 320.

PMID- 18626643
TI  - Efficient secretion of Bacillus subtilis lipase A in Saccharomyces cerevisiae by
      translational fusion to the Pir4 cell wall protein.
AB  - Both the secretion and the cell surface display of Bacillus subtilis lipase A
      (Lip A) in Saccharomyces cerevisiae was investigated using different domains of
      the cell wall protein Pir4 as translational fusion partners. LipA gene minus its
      leader peptide was fused inframe in two places of PIR4 to achieve cell wall
      targeting, or substituting most of the PIR4 sequence, after the signal peptide
      and the Kex2 processed subunit I of Pir4 to achieve secretion to the growth
      medium. Expression of the recombinant fusion proteins was investigated in a
      standard and a glycosylation-deficient strain of S. cerevisiae, grown in
      selective or rich medium. Fusion proteins intended to be retained at the cell
      wall were secreted to the growth medium, most likely as result of the degradation
      of the Pir4 moiety containing the cell wall retention domain, giving low levels
      of lipase activity. However, the fusion intended for secretion was efficiently
      secreted in a percentage of close to 90% and remained stable even in rich medium
      at high cell density cultures, yielding values of over 400 IU of lipase activity
      per milliliter of cell supernatant. This is, to our knowledge, the first report
      of the efficient production, as a secreted protein, of lipase A of B. subtilis in
      baker's yeast.

PMID- 18626644
TI  - A user's guide to PDE models for chemotaxis.
AB  - Mathematical modelling of chemotaxis (the movement of biological cells or
      organisms in response to chemical gradients) has developed into a large and
      diverse discipline, whose aspects include its mechanistic basis, the modelling of
      specific systems and the mathematical behaviour of the underlying equations. The
      Keller-Segel model of chemotaxis (Keller and Segel in J Theor Biol 26:399-415,
      1970; 30:225-234, 1971) has provided a cornerstone for much of this work, its
      success being a consequence of its intuitive simplicity, analytical tractability
      and capacity to replicate key behaviour of chemotactic populations. One such
      property, the ability to display "auto-aggregation", has led to its prominence as
      a mechanism for self-organisation of biological systems. This phenomenon has been
      shown to lead to finite-time blow-up under certain formulations of the model, and
      a large body of work has been devoted to determining when blow-up occurs or
      whether globally existing solutions exist. In this paper, we explore in detail a
      number of variations of the original Keller-Segel model. We review their
      formulation from a biological perspective, contrast their patterning properties,
      summarise key results on their analytical properties and classify their solution
      form. We conclude with a brief discussion and expand on some of the outstanding
      issues revealed as a result of this work.

PMID- 18626645
TI  - Disease-induced mortality in density-dependent discrete-time S-I-S epidemic
      models.
AB  - The dynamics of simple discrete-time epidemic models without disease-induced
      mortality are typically characterized by global transcritical bifurcation. We
      prove that in corresponding models with disease-induced mortality a tiny number
      of infectious individuals can drive an otherwise persistent population to
      extinction. Our model with disease-induced mortality supports multiple
      attractors. In addition, we use a Ricker recruitment function in an SIS model and
      obtained a three component discrete Hopf (Neimark-Sacker) cycle attractor
      coexisting with a fixed point attractor. The basin boundaries of the coexisting
      attractors are fractal in nature, and the example exhibits sensitive dependence
      of the long-term disease dynamics on initial conditions. Furthermore, we show
      that in contrast to corresponding models without disease-induced mortality, the
      disease-free state dynamics do not drive the disease dynamics.

PMID- 18626646
TI  - Roles of microRNA in plant defense and virus offense interaction.
AB  - MicroRNAs (miRNA) that are around 22 nucleotides long non-protein-coding RNAs,
      play key regulatory roles in plants. Recent research findings show that miRNAs
      are involved in plant defense and viral offense systems. Advances in
      understanding the mechanism of miRNA biogenesis and evolution are useful for
      elucidating the complicated roles they play in viral infection networks. In this
      paper a brief summary of evolution of plant anti-virus defense is given and the
      function of miRNAs involved in plant-virus competition is highlighted. It is
      believed that miRNAs have several advantages over homology-dependent and siRNA
      mediated gene silencing when they are applied biotechnologically to promote plant
      anti-virus defense. miRNA-mediated anti-virus pathway is an ancient mechanism
      with a promising future. However, using miRNAs as a powerful anti-virus tool will
      be better realized only if miRNA genomics and functions in plant viral infection
      are fully understood.

PMID- 18626647
TI  - Production and characterization of intergeneric somatic hybrids between Brassica
      napus and Orychophragmus violaceus and their backcrossing progenies.
AB  - Alien chromosome addition lines have been widely used for identifying gene
      linkage groups, assigning species-specific characters to a particular chromosome
      and comparing gene synteny between related species. In plant breeding, their
      utilization lies in introgressing characters of agronomic value. The present
      investigation reports the production of intergeneric somatic hybrids Brassica
      napus (2n = 38) + Orychophragmus violaceus (2n = 24) through asymmetric fusions
      of mesophyll protoplasts and subsequent development of B. napus-O. violaceous
      chromosome addition lines. Somatic hybrids showed variations in morphology and
      fertility and were mixoploids (2n = 51-67) with a range of 19-28 O. violaceus
      chromosomes identified by genomic in situ hybridization (GISH). After pollinated
      with B. napus parent and following embryo rescue, 20 BC(1) plants were obtained
      from one hybrid. These exhibited typical serrated leaves of O. violaceus or B.
      napus-type leaves. All BC(1) plants were partially male fertile but female
      sterile because of abnormal ovules. These were mixoploids (2n = 41-54) with 9-16
      chromosomes from O. violaceus. BC(2) plants showed segregations for female
      fertility, leaf shape and still some chromosome variation (2n = 39-43) with 2-5
      O. violaceus chromosomes, but mainly containing the whole complement from B.
      napus. Among the selfed progenies of BC(2) plants, monosomic addition lines (2n =
      39, AACC + 1O) with or without the serrated leaves of O. violaceus or female
      sterility were established. The complete set of additions is expected from this
      investigation. In addition, O. violaceus plants at diploid and tetraploid levels
      with some variations in morphology and chromosome numbers were regenerated from
      the pretreated protoplasts by iodoacetate and UV-irradiation.

PMID- 18626648
TI  - Stable genetic transformation of castor (Ricinus communis L.) via particle gun
      mediated gene transfer using embryo axes from mature seeds.
AB  - The first successful attempt to produce stably transformed castor plants through
      direct gene transfer using particle gun (BioRad) is described. Decotyledonated
      embryos from mature seeds were germinated and the embryonic axis was induced to
      proliferate on Murashige and Skoog (MS) medium supplemented with 0.5 mg l(-1)
      thidiazuron (TDZ) and subjected to bombardment after 5-7 days of pre-incubation.
      The physical parameters for transient transformation were optimized using the
      UidA gene encoding beta-glucuronidase (GUS) as the reporter gene and with
      hygromycin-phosphotransferase (hptII) gene as selectable marker. Statistical
      analysis revealed that helium pressure, target distance, osmoticum, microcarrier
      type and size, DNA quantity, explant type and number of bombardments had
      significant influence on transformation efficiency, while the effect of genotype
      was non-significant. Of the different variables evaluated, embryonic axes from
      mature seeds, a target distance of 6.0 cm, helium pressure of 1,100 psi, 0.6
      microm gold microcarriers, single time bombardment and with both pre- and post
      osmoticum were found ideal. Selection of putative transformants was done on MS
      medium supplemented with 0.5 mg l(-1) BA and hygromycin (20, 40 and 60 mg l(-1))
      for 3 cycles. The stable integration of the incorporated gene into castor genome
      was confirmed with PCR and Southern analysis of T0 and T1 plants. Transformation
      frequency in terms of plants grown to maturity and showing the presence of the
      introduced genes was 1.4%. The present results demonstrate the possibility of
      transformation of embryonic meristematic tissues of castor through particle
      delivery system.

PMID- 18626649
TI  - Physiological flexibility in the Andean lizard Liolaemus bellii: seasonal changes
      in energy acquisition, storage and expenditure.
AB  - According to the "barrel model", an organism may be represented by a container,
      with input energy constraints (foraging, digestion, and absorption) symbolized by
      funnels connected in tandem, and energy outputs (maintenance, growth, and
      reproduction) symbolized by a series of spouts arranged in parallel. Animals can
      respond to changes in environmental conditions, through adjustments in the size
      of the funnels, the fluid stored inside the barrel, or the output flow through
      the spouts. In the present study, we investigate the interplay among these
      processes through the analysis of seasonal changes in organ size and metabolic
      rate in a lizard species (Liolaemus bellii) that inhabits extremely seasonal
      environments in the Andes range. We found that digestive organ size showed the
      greatest values during spring and summer, that is, during the foraging seasons.
      Energy reserves were larger during summer and autumn, and then decreased through
      winter and spring, which was correlated with overwintering maintenance and
      reproductive costs. Standard metabolic rate was greater during the high-activity
      seasons (spring and summer), but this increase was only noticeable at higher
      environmental temperatures. The ability of many lizard species to reduce their
      maintenance cost during the cold months of the year, beyond what is expected from
      temperature decrease, is probably related to their success in coping with highly
      fluctuating environments. Here, we demonstrate that this ability is correlated
      with high physiological flexibility, which allows animals to adjust energy
      acquisition, storing and expenditure processes according to current environmental
      conditions.

PMID- 18626650
TI  - Chiari I malformation without hydrocephalus: acute intracranial hypertension
      managed with endoscopic third ventriculostomy (ETV).
AB  - INTRODUCTION: In a small subset of patients, a Chiari malformation can present
      with signs of raised intracranial pressure due to obstruction of cerebrospinal
      fluid flow or with the raised intracranial pressure as the primary pathological
      driving force resulting in tonsillar herniation. CASE REPORT: The authors report
      a unique case in a 14-year-old boy with a Chiari malformation type 1
      syringomyelia complex with slit-like ventricles. We have successfully managed the
      acute presentation of raised intracranial pressure, mimicking idiopathic
      intracranial hypertension, utilizing a frameless stereotactic image-navigated
      endoscopic third ventriculostomy alone. We present the preoperative and
      postoperative radiological and ophthalmological findings and discuss the possible
      mechanisms related to the pathophysiology and treatment in this case. The
      patient's symptoms resolved immediately postoperatively with resolution of
      papilledema. At 18-month follow-up, the patient remains entirely asymptomatic and
      the need for craniovertebral decompression appears to have been obviated.
      CONCLUSION: We advocate that in the Chiari malformation type 1-syringomyelia
      complex with normal or small ventricles, patients presenting with isolated signs
      and symptoms of raised intracranial pressure alone can be safely and effectively
      managed with an electromagnetic-guided stereotactic endoscopic third
      ventriculostomy as a primary treatment option.

PMID- 18626651
TI  - Evaluation of alpha-synuclein immunohistochemical methods used by invited
      experts.
AB  - The use of alpha-synuclein immunohistochemistry has altered our concepts of the
      cellular pathology, anatomical distribution and prevalence of Lewy body
      disorders. However, the diversity of methodology between laboratories has led to
      some inconsistencies in the literature. Adoption of uniformly sensitive methods
      may resolve some of these differences. Eight different immunohistochemical
      methods for demonstrating alpha-synuclein pathology, developed in eight separate
      expert laboratories, were evaluated for their sensitivity for neuronal elements
      affected by human Lewy body disorders. Identical test sets of formalin-fixed,
      paraffin-embedded sections from subjects diagnosed neuropathologically with or
      without Lewy body disorders were stained with the eight methods and graded by
      three observers for specific and nonspecific staining. The methods did not differ
      significantly in terms of Lewy body counts, but varied considerably in their
      ability to reveal neuropil elements such as fibers and dots. One method was
      clearly superior for revealing these neuropil elements and the critical factor
      contributing to its high sensitivity was considered to be its use of proteinase K
      as an epitope retrieval method. Some methods, however, achieved relatively high
      sensitivities with optimized formic acid protocols combined with a hydrolytic
      step. One method was developed that allows high sensitivity with commercially
      available reagents.

PMID- 18626652
TI  - High revision rate after treatment of femoral neck fractures with an optionally
      (un)cemented stem.
AB  - BACKGROUND: The advantages of uncemented and cemented components in hip
      arthroplasty have been subject of debate. We have studied on a hemiprosthesis,
      which can be optionally implanted with or without cement. Since the stem geometry
      and surface in cemented arthroplasty differs from the uncemented one and cannot
      be fused into one general design, we hypothesised that this hemiprosthesis used
      without cement has a considerable high revision rate, based on aseptic loosening.
      METHODS: A hemiprosthesis, which is designed for both cemented and uncemented
      fixation, was used (Conquest, Smith&Nephew). Preoperatively, the choice of
      whether to use cement or not was based on the shape and bone quality of the
      femoral canal. Revision rate and indication, mortality, perioperative
      complications and radiographic features of 151 consecutive hips in 146 patients
      were evaluated. RESULTS: Twenty-three stems (15%) were implanted with cement and
      128 (85%) without. After a mean follow-up of 2 years, a revision rate of 8.6% and
      a survival percentage of 90% (CI 85-95) were observed. Twelve uncemented stems
      warranted revision, compared with one cemented stem. Revision because of aseptic
      loosening was necessary in 7 (6%) stems, all uncemented. No differences in
      operation-related mortality and morbidity were observed. CONCLUSION: Because of
      the rather high revision rate, the authors advice not to use this hemiprosthesis
      without cement.

PMID- 18626653
TI  - Bilateral promontory fistula due to noncholesteatomatous chronic otitis media.
AB  - The authors describe a case of bilateral promontory fistula due to
      noncholesteatomatous chronic otitis media in a 46-year-old male. We performed
      both open cavity mastoidectomy and left staged ossiculoplasty. One year
      postoperatively, the audiogram showed an improved left air conduction threshold
      and maintenance of bone conduction. We suggest that noncholesteatomatous chronic
      otitis media can induce various destructive changes via the chronic inflammatory
      reaction.

PMID- 18626654
TI  - The use of "harmonic scalpel" versus "knot tying" for conventional "open"
      thyroidectomy: results of a prospective randomized study.
AB  - PURPOSE: We evaluated the safety and cost-effectiveness of the harmonic scalpel
      (HS) during conventional "open" thyroidectomy (CT). MATERIALS AND METHODS: Two
      hundred patients scheduled for conventional total thyroidectomy (TT) were
      included in the study and randomly assigned to TT with the use of HS (HS group)
      or with knot tying technique (KT group). RESULTS: Mean operative time was
      significantly shorter in the HS group (P < 0.001), as well as the total operative
      room occupation time (P < 0.001). The cost of the disposable materials is
      significantly higher in the HS group (420.1 +/- 23.2 vs 137.8 +/- 25.3 euros; P <
      0.001). Conversely, drugs, personnel and operative room charges were
      significantly higher in KT group patients (P < 0.001). Overall, no significant
      difference was found between the two groups concerning the charges of the
      hospitalisation (P = NS). CONCLUSIONS: HS is a safe alternative to KT, allowing
      for a significant reduction of operative time without increasing complications
      rate and overall costs and probably better utilization of health resources.

PMID- 18626655
TI  - 99Tc Nanocolloid sentinel node procedure in thyroid carcinoma.
AB  - PURPOSE: The purposes of this study were to investigate the efficacy of
      radiocolloid lymphoscintigraphy and of handheld gamma probe procedure for
      sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC) and to
      evaluate its results in clinical staging. MATERIALS AND METHODS: Sixty-five PTC
      consecutive patients entered the study. Patients underwent radiocolloid
      lymphoscintigraphy before surgery. Intraoperative sentinel lymph node (SLN)
      localization was performed using a handheld gamma probe. They were followed up at
      2, 6 months, and yearly. RESULTS: SLN metastases were diagnosed in 52%. Fifty-one
      patients underwent ablative 131-I therapy. The mean Tireoglobulin level in N0 vs
      N1 cases was 2.2 ng/ml vs 4.73 (p = 0.03) and 0.68 vs 2.1 ng/ml (p = 0.005)
      before and after 131-I therapy, respectively. CONCLUSIONS: In patients classified
      N0 by SLNB, ablative 131-I therapy could be avoided.

PMID- 18626656
TI  - Can the early reduction of tumour markers predict outcome in surgically treated
      sporadic medullary thyroid carcinoma?
AB  - BACKGROUND AND AIMS: Patients with sporadic medullary thyroid carcinoma (MTC)
      have a variable clinical course. Our aim was to analyse the reduction of tumour
      markers after thyroidectomy with meticulous dissection and relate it to clinical
      outcome. MATERIALS AND METHODS: Twenty consecutive patients with palpable
      sporadic MTC underwent thyroidectomy with central and uni- or bilateral modified
      radical neck dissection; three were subjected to mediastinal dissection. Basal (b
      ) and stimulated (s-) calcitonin (CT) and carcinoembryonic antigen (CEA)-levels
      were measured before and 6-8 weeks after primary surgery, and the reduction of
      these tumour markers was determined. RESULTS: Median CT (b- and s-) were markedly
      reduced after surgery (98.5% and 99.1%, respectively), and CEA decreased 11
      times. CT (b-) fell >99% in seven patients after surgery; in these and four
      additional patients, CT (s-) showed a similar reduction. During follow-up (median
      52.5 months), two patients (stages IV B and C) died of MTC; they had <95%
      reduction of CT. Four patients (stage IV A) are alive with verified metastases.
      Eight patients (one stage III, seven stage IV A) are alive with
      hypercalcitoninemia. Five stages I-III patients and one stage IV A patient are
      disease-free. CONCLUSIONS: Thyroidectomy and meticulous dissection caused a
      pronounced reduction of tumour markers. A postoperative reduction of CT (s-)
      >or=97% seems to be associated with less aggressive clinical course, while CEA
      had lower predictive value.

PMID- 18626657
TI  - Occult disseminated tumor cells in lymph nodes of patients with gastric
      carcinoma. A critical appraisal of assessment and relevance.
AB  - BACKGROUND AND AIMS: In gastric cancer, regional lymph node metastasis verified
      by histopathological examination is the most important prognostic factor after
      complete surgical tumor resection (R0). However, the prognostic value of
      immunohistochemically identifiable disseminated tumor cells in lymph nodes
      without histopathological tumor burden in patients with gastric cancer is still
      controversially discussed. The aim of the study was to assess the frequency and
      prognostic impact of minimal tumor cell spread to lymph nodes in these patients.
      PATIENTS-METHODS: One hundred sixty lymph nodes judged as "tumor free" on routine
      histopathology obtained from 58 patients with gastric adenocarcinoma were
      analyzed immunohistochemically using the monoclonal anti-EpCAM antibody Ber-EP4
      for occult disseminated tumor cells. RESULTS: Tumor cells in lymph nodes were
      detected in 62 (38.8%) of the 160 "tumor-free" lymph nodes obtained from 39
      (67.2%) patients. Multivariate Cox regression analysis confirmed the presence of
      disseminated tumor cells in "tumor-free" lymph nodes as an independent prognostic
      factor for both a significantly reduced relapse-free survival (p = 0.008) and
      overall survival (p = 0.009). CONCLUSIONS: The frequent occurrence and prognostic
      impact of minimal disseminated tumor cells in lymph nodes of patients with
      gastric carcinoma support the need for a refined staging system of excised lymph
      nodes, which should include immunohistochemical examination.

PMID- 18626659
TI  - Does unconscious thought improve complex decision making?
AB  - In a recent study, Dijksterhuis et al. (Science 311:1005, 2006) reported that
      participants were better at solving complex decisions after a period of
      unconscious thought relative to a period of conscious thought. They interpreted
      their results as an existence proof of powerful unconscious deliberation
      mechanisms. In the present report, we used a similar experimental design with an
      additional control, immediate condition, and we observed that participants
      produced as good (and even descriptively better) decisions in this condition than
      in the "unconscious" one, hence challenging the initial interpretation of the
      authors. However, we still obtained lower performances in the "conscious"
      relative to the "immediate" condition, suggesting that the initial result of
      Dijksterhuis et al. was not due to the action of powerful unconscious thought
      processes, but to the apparent disadvantage of further conscious processing. We
      provide an explanation for this observation on the basis of current models of
      decision making. It is finally concluded that the benefit of unconscious thought
      in complex decision making is still a controversial issue that should be
      considered cautiously.

PMID- 18626658
TI  - Fatty acids do not activate UCP2 in pancreatic beta cells: comparison with UCP1.
AB  - UCP2 is expressed in pancreatic beta cells where its postulated uncoupling
      activity will modulate glucose-induced changes in ATP/ADP ratio and insulin
      secretion. The consequences of UCP2 over/underexpression on beta-cell function
      has mainly been studied in the basal state; however, a UCP has no uncoupling
      activity unless stimulated by fatty acids and/or reactive oxygen species. Here,
      UCP2 was overexpressed in INS-1 cells and parameters reflecting mitochondrial
      coupling measured in the basal state and after stimulation by fatty acids. For
      comparison, UCP1 was expressed to similar levels and the same parameters
      measured. Neither UCP1 expression nor UCP2 overexpression modified basal or
      glucose-stimulated metabolic changes. Upon addition of fatty acids, UCP1
      expressing cells displayed the expected mitochondrial uncoupling effect, while
      UCP2 did not elicit any measurable change in mitochondrial function. Taken
      together, our data demonstrate that, in pancreatic beta-cells, UCP2 has no
      uncoupling activity in the basal state or after fatty acid stimulation.

PMID- 18626660
TI  - Serum vascular endothelial growth factor: a prognostic factor in cervical cancer.
AB  - PURPOSE: To study pre-treatment serum VEGF of patients with invasive cervical
      cancer and its possible role as prognostic indicator. METHODS: VEGF was measured
      using ELISA in the largest patient group (n = 167) to date. RESULTS: Serum VEGF
      was significantly higher in advanced tumor stage (P = 0.01), large tumor size
      (tumors larger than 2 cm) (P = 0.03), and the presence of vascular space invasion
      (P = 0.05). Serum VEGF was associated with disease free and overall survival
      [DFS: Hazard Ratio (HR) = 2.61; 95% CI 1.32-5.17; P = 0.006; for OS: HR = 2.09;
      95% CI 1.54-2.84; P < 0.001, respectively]. In multivariate Cox regression serum
      VEGF retained its prognostic value for DFS (HR = 2.10, P = 0.03) and OS (HR =
      1.92, P = 0.04). CONCLUSIONS: Serum VEGF levels correlate with more advanced and
      more aggressive disease in cervical cancer and may be a useful prognostic factor
      in patients with cervical cancer.

PMID- 18626661
TI  - Recognition and characterization of TGF-beta receptor interacting protein 1 (TRIP
      1) containing WD40 repeats from Clonorchis sinensis by bioinformatics, cloning,
      and expression in Escherichia coli.
AB  - A cDNA clone encoding a homologue of transforming growth factor beta (TGF-beta)
      receptor interacting protein 1 (TRIP-1) was recognized and isolated from full
      length cDNA plasmid library of Clonorchis sinensis adult. TRIP-1 is a
      bifunctional molecule in all eukaryote, which modulates the signaling pathway of
      TGF-beta as a phosphorylation substrate of TGF-beta type II receptor kinase and
      controls ribosome assembly and mRNA translation as p36 subunit of the eukaryotic
      translation initiation factor 3. The structural and immunological characteristics
      of TRIP-1 from C. sinensis (CsTRIP-1) were analyzed by bioinformatics. The
      complete coding sequence was expressed in Escherichia coli, and the purified
      recombinant product was obtained. Western blotting with mixed sera from
      clonorchiasis patients was positive, whereas the normal was negative, suggesting
      it is a candidate of diagnostic antigen for clonorchiasis. CsTRIP-1 will aid to
      explore interaction between host and the parasite as well as the mechanism by
      which TGF-beta controls the development of C. sinensis and participates in the
      pathogenesis.

PMID- 18626662
TI  - Elucidation of genetic variability among different isolates of Fasciola gigantica
      (giant liver fluke) using random-amplified polymorphic DNA polymerase chain
      reaction.
AB  - The present communication focuses on molecular characterization of Fasciola
      gigantica isolates derived from cattle, buffalo, and goat using random-amplified
      polymorphic DNA (RAPD)-polymerase chain reaction (PCR) analysis to elucidate
      genetic variability between the three isolates. Seventeen random oligonucleotide
      primers of 10-11 bases with GC content varying from 50-81.8% were used in the
      study. Depending upon the F. gigantica isolate-primer combination, one to five
      fragments in the range of 327-1,973 bp were amplified. It was significant to
      observe that, out of the 17 primers directing amplification of DNA fingerprints,
      only two designated as AP9 and AP14 were found to be of potential interest in the
      generation of polymorphic DNA. On the basis of similarity coefficient data, it
      may be suggested that cattle and buffalo isolates of F. gigantica show 100%
      homogeneity against 92.68% similarity coefficient observed between goat and
      cattle/buffalo isolates. In other words, 7.32% divergence was observed between
      goat and cattle/buffalo isolates while the primers AP1, AP4, AP10, AP13, and AP17
      were able to generate monomorphic DNA fingerprints. Primers AP9 and AP14 are
      potentially informative in terms of the polymorphic nature of the fingerprints
      generated in RAPD assays. The finding of the absence of 626-bp DNA fragment in
      the goat and the uniqueness of the AP14 in generating a single RAPD-PCR product
      of 1,211 bp as against the product size of 1,162 bp in cattle/buffalo seem to be
      significant. This is the first report of elucidation of RAPD-PCR based molecular
      variability in the DNA fingerprinting pattern of F. gigantica isolated from
      cattle, buffalo, and goat.

PMID- 18626663
TI  - The key steroidogenic enzyme 3beta-hydroxysteroid dehydrogenase in Taenia solium
      and Taenia crassiceps (WFU).
AB  - Larval and adult stages of Taenia solium and Taenia crassiceps WFU strain were
      analyzed by histochemical and biochemical methods to determine the existence of
      steroid pathways. The presence of the key enzyme 3beta-hydroxisteroid
      dehydrogenase (3beta-HSD) was examined in frozen sections of cysticerci obtained
      from mice and segments of tapeworms obtained from the intestine of hamsters.
      3beta-HSD activity was detected by nitroblue-tetrazolium products after
      incubation with dehydroepiandrosterone, androstendiol, or pregnenolone. Tapeworm
      tissues exhibited 3beta-HSD activity in the subtegumentary areas of the neck and
      immature proglottids following incubation with androstendiol, as well as
      surrounding the testes in mature proglottids. T. solium cysticerci exhibited
      3beta-HSD activity in the subtegumentary tissues. The synthesis of steroid
      hormones involving the activity of 3beta-HSD was studied in cysticerci or
      tapeworms incubated in the presence of tritiated steroid precursors. The culture
      media were analyzed by thin layer chromatography and showed synthesis of
      androstendiol, testosterone, and 17beta-estradiol by cysticerci, androstendiol,
      and 17beta-estradiol by tapeworms. The results strongly suggest the activity of
      3beta-HSD in taeniid parasites that have at least a part of the enzymatic chain
      required for androgen and estrogen synthesis and that the enzymes are present in
      the larval stage and from the early strobilar stages to the mature proglottids.

PMID- 18626664
TI  - Transmission electron microscopic studies of stages of Histomonas meleagridis
      from clonal cultures.
AB  - Histomonas meleagridis is a 10-20 microm-sized flagellated protozoan, causing
      histomoniasis in gallinaceous birds. Different strains of H. meleagridis from
      different origins were used to establish clonal cultures, which can be traced
      back to a single cell. Cells from these clonal cultures were examined by
      transmission electron microscopy. Results gave detailed insights in the
      ultrastructure showing a single flagellum, a band of microtubules remnants of an
      axostyle or of a costa, respectively pelta, hydrogenosomes, nucleus, spindle
      apparatus, and other organelles of the trophozoites of H. meleagridis.

PMID- 18626665
TI  - A simplified model to predict diurnal water temperature dynamics in a shallow
      tropical water pool.
AB  - Water temperature is a critical regulator in the growth and development of
      malaria mosquito immatures, as they are poikilothermic. Measuring or estimating
      the diurnal temperature ranges to which these immatures are exposed is of the
      utmost importance, as these immatures will develop into adults that can transmit
      malaria. Recent attempts to predict the daily water temperature dynamics in
      mosquito breeding sites in Kenya have been successful. However, the developed
      model may be too complex, as the sophisticated equipment that was used for
      detailed meteorological observations is not widely distributed in Africa, making
      it difficult to predict the daily water temperature dynamics on a local scale.
      Therefore, we compared two energy budget models with earlier made observations of
      the daily water temperature dynamics in a small, shallow and clear water pool
      (diameter 0.96 m, depth 0.32 m) in Kenya. This paper describes (1) a complex 1
      Dimensional model, and (2) a simplified second model, and (3) shows that both
      models mimic the water temperature dynamics in the water pool accurately. The
      latter model has the advantage that it only needs common weather data (air
      temperature, air humidity, wind speed and cloud cover) to estimate the diurnal
      temperature dynamics in breeding sites of African malaria mosquitoes.

PMID- 18626666
TI  - Development and evaluation of a problem-focused psychosocial intervention for
      patients with head and neck cancer.
AB  - GOALS OF THE WORK: Patients with head and neck cancer have complex needs that
      affect many basic functions of life and contribute to substantial psychosocial
      problems. The aim of this study was to evaluate the effectiveness of a problem
      focused intervention for patients with psychosocial dysfunction who had completed
      treatment for head and neck cancer. PATIENTS AND METHODS: Using a quasi
      experimental design, 54 participants who were above pre-determined cutoff points
      for psychosocial dysfunction (hospital and depression scale, work and social
      adjustment scale) were given the opportunity to self-select into either the
      experimental group for the psychosocial intervention programme which was
      delivered in an individualised format, with bibliotherapy as an adjunct, or the
      control group for usual care. MAIN RESULTS: Analysis of covariance results
      demonstrated a reduction in psychological distress (anxiety, p = 0.001;
      depression, p = 0.005), improving social functioning (p = 0.048) and quality of
      life scores (p = <0.05) for the experimental group, all of which were sustained
      into the 3-month follow-up period. No such improvements were evident for the
      control group. CONCLUSIONS: This study suggests that head and neck cancer
      patients with post-treatment psychosocial dysfunction can benefit from a problem
      focused psychosocial intervention. Such evidence can inform practice, policy and
      future research, aimed at improving post-treatment quality of life for patients
      with head and neck cancer.

PMID- 18626667
TI  - Development and validation of the system of quality of life instruments for
      cancer patients: breast cancer (QLICP-BR).
AB  - GOALS: To develop and validate a quality of life (QOL) instrument for patients
      with breast cancer, QLICP-BR, which is one of the system of QOL instruments for
      cancer patients in China. METHODS: Using the programmed decision methods of
      instrument development, the quality of life instrument for cancer patients-breast
      cancer (QLICP-BR) with considering Chinese cultural background was developed, and
      evaluated on the data from 186 inpatients with breast cancer. The statistical
      methods used in this research included statistical description, Pearson
      correlation, factor analysis, and paired t test. RESULTS: The test-retest
      reliability for the overall scale and five domains are all above 0.75. Internal
      consistency alpha for each domain is higher than 0.65 except social domain
      (0.58). Most correlation coefficients between each item and it's domain are above
      0.60. The scores differences between pretreatment and post-treatment for overall
      scale, general module, physical domain, psychological domain and social domain
      have statistical significance. CONCLUSIONS: The QLICP-BR is of good validity,
      reliability, and reasonable responsiveness, and can be used to assess quality of
      life for patients with breast cancer in China.

PMID- 18626668
TI  - A computational investigation of sulfur-containing heterocyclic components from
      the anal sac secretions of Mustela species.
AB  - A computational investigation of the sulfur-containing heterocyclic components
      (substituted thietanes and 1,2-dithiolanes) of Mustela anal sac secretions has
      been carried out. A cluster analysis of the chemical compositions of Mustela anal
      sac volatiles reveals little similarity with established phylogenetic
      relationships between members of the genus. Ab initio calculations [MP2/6
      311++G(2df,2p)//B3LYP/6-311++G**] show the lowest-energy C5H10S isomeric thietane
      to be 2,2-dimethylthietane, which is also the most abundant of the Mustela
      thietanes. Similarly, 3,3-dimethyl-1,2-dithiolane is the lowest-energy C5H10S2
      compound. 2-n-Propylthietane is the highest-energy C6H12S compound, but the most
      abundant Mustela C6H12S compound produced, whereas cis-2-ethyl-4-methylthietane,
      the lowest-energy C6H12S thietane, has never been observed in Mustela anal sac
      secretions. A molecular docking analysis of the Mustela sulfur-containing
      heterocycles into both porcine and bovine odorant binding proteins reveals the
      interactions of the docked ligands with the proteins to be largely hydrophobic,
      and have binding energies generally lower than typical odorant molecules such as
      linalool or eugenol.

PMID- 18626670
TI  - The electronic structure of the C2H4O...2HF tri-molecular heterocyclic hydrogen
      bonded complex: a theoretical study.
AB  - The geometries of three isomers of the C2H4O...2HF tri-molecular heterocyclic
      hydrogen-bonded complex were examined through B3LYP/aug-cc-pVDZ calculations.
      Analysis of structural parameters, determination of CHELPG (charge electrostatic
      potential grid) intermolecular charge transfer, interpretation of infrared
      stretching modes, and Bader's atoms in molecules (AIM) theory calculations was
      carried out in order to characterize the hydrogen bonds in each isomer of the
      C2H4O...2HF complex. The most stable structure was determined through the
      identification of hydrogen bonds between C2H4O and HF, (O...H), as well as in the
      hydrofluoric acid dimer, (HF(D-R)...HF(D)). However, the existence of a tertiary
      interaction (F(lambda)...H(alpha)) between the fluoride of the second
      hydrofluoric acid and the axial hydrogen atoms of C2H4O was decisive in the
      identification of the preferred configuration of the C2H4O...2HF system.

PMID- 18626669
TI  - Computational studies of the binding site of alpha1A-adrenoceptor antagonists.
AB  - Aimed at achieving a good understanding of the 3-dimensional structures of human
      alpha1A-adrenoceptor (alpha1A-AR), we have successfully developed its homology
      model based on the crystal structure of beta2-AR. Subsequent structural
      refinements were performed to mimic the receptor's natural membrane environment
      by using molecular mechanics (MM) and molecular dynamics (MD) simulations in the
      GBSW implicit membrane model. Through molecular docking and further simulations,
      possible binding modes of subtype-selective alpha1A-AR antagonists, Silodosin,
      RWJ-69736 and (+)SNAP-7915, were examined. Results of the modeling and docking
      studies are qualitatively consistent with available experimental data from
      mutagenesis studies. The homology model built should be very useful for designing
      more potent subtype-selective alpha1A-AR antagonists and for guiding further
      mutagenesis studies.

PMID- 18626671
TI  - Molecular docking guided 3D-QSAR CoMFA analysis of N-4-Pyrimidinyl-1H-indazol-4
      amine inhibitors of leukocyte-specific protein tyrosine kinase.
AB  - Inhibition of leukocyte-specific protein tyrosine kinase (Lck) activity offers
      one of the approaches for the treatment of T-cell mediated inflammatory disorders
      including rheumatoid arthritis, transplant rejection and inflammatory bowel
      disease. To explore the relationship between the structures of the N-4
      Pyrimidinyl-1H-indazol-4-amines and their Lck inhibition, 3D-QSAR study using
      CoMFA analysis have been performed on a dataset of 42 molecules. The bioactive
      conformation of the template molecule, selected as the most potent molecule 23
      from the series was obtained by performing molecular docking at the ATP binding
      site of Lck, which is then used to build the rest of the molecules in the series.
      The constructed CoMFA model is robust with r(2)(cv) of 0.603 and conventional r2
      of 0.983. The predictive power of the developed model was obtained using a test
      set of 10 molecules, giving predictive correlation coefficient of 0.921. CoMFA
      contour analysis was performed to obtain useful information about the structural
      requirements for the Lck inhibitors which could be utilized in its future design.

PMID- 18626672
TI  - CoMFA based de novo design of pyrrolidine carboxamides as inhibitors of enoyl
      acyl carrier protein reductase from Mycobacterium tuberculosis.
AB  - InhA, the enoyl acyl carrier protein reductase (EACP reductase) from
      Mycobacterium tuberculosis, is one of the key enzymes involved in the
      mycobacterial fatty acid elongation cycle and has been validated as an effective
      target for the development of anti-microbial agents. We report here, comparative
      molecular field analysis (CoMFA) studies and subsequent de novo ligand design
      using the LeapFrog program on pyrrolidine carboxamides, which have been reported
      as selective inhibitors of EACP reductase from Mycobacterium tuberculosis. The
      CoMFA model, constructed from the inhibitors used in this study has been
      successfully used to rationalize the structure-activity relationship of
      pyrrolidine carboxamides. The CoMFA model produced statistically significant
      results with cross-validated and conventional correlation coefficients of 0.626
      and 0.953 respectively. Further, the predictive ability of CoMFA model was
      determined using a test set which gave predictive correlation coefficient r2
      (pred) of 0.880, indicating good predictive power. Finally, Leapfrog was used to
      propose 13 new pyrrolidine carboxamide analogues, based on the information
      derived from the CoMFA contour maps. The designed molecules showed better
      predicted activity using the CoMFA model with respect to the already reported
      systems; hence suggesting that newly proposed molecules in this series of
      compounds may be more potent and selective toward EACP reductase inhibition.

PMID- 18626673
TI  - Role of Mycoplasma pneumoniae in pediatric encephalitis.
AB  - A retrospective study investigating all the infectious encephalitis cases
      hospitalized at the pediatric intensive care unit of Edouard Herriot University
      Hospital in Lyon, France, was carried out in order to estimate the prevalence of
      Mycoplasma pneumoniae in acute childhood encephalitis. From January 2001 to
      December 2005, the cases of 29 children were selected and reviewed. M. pneumoniae
      related encephalitis was considered as probable in five cases (17%) on the basis
      of positive serological tests or positive polymerase chain reaction (PCR) tests
      in throat or nasopharyngeal swab while the PCR tests performed from the
      cerebrospinal fluid were negative. This study suggests that M. pneumoniae may be
      a major cause of infectious encephalitis in children as well as enteroviruses or
      Epstein-Barr virus detected in five and three cases, respectively.

PMID- 18626674
TI  - How to reason without words: inference as categorization.
AB  - The idea that reasoning is a singular accomplishment of the human species has an
      ancient pedigree. Yet this idea remains as controversial as it is ancient. Those
      who would deny reasoning to nonhuman animals typically hold a language-based
      conception of inference which places it beyond the reach of languageless
      creatures. Others reject such an anthropocentric conception of reasoning on the
      basis of similar performance by humans and animals in some reasoning tasks, such
      as transitive inference. Here, building on the modal similarity theory of Vigo [J
      Exp Theor Artif Intell, 2008 (in press)], we offer an account in which reasoning
      depends on a core suite of subsymbolic processes for similarity assessment,
      discrimination, and categorization. We argue that premise-based inference
      operates through these subsymbolic processes, even in humans. Given the robust
      discrimination and categorization abilities of some species of nonhuman animals,
      we believe that they should also be regarded as capable of simple forms of
      inference. Finally, we explain how this account of reasoning applies to the kinds
      of transitive inferences that many nonhuman animals display.

PMID- 18626675
TI  - Artificial neural network: border detection in echocardiography.
AB  - Being non-invasive and low cost, the echocardiography has become a diagnostic
      technique largely applied for the determination of the left ventricle systolic
      and diastolic volumes, which are used indirectly to calculate the left ventricle
      ejection volume, the cardiac cavities muscular contraction, the regional ejection
      fraction, the myocardial thickness, and the ventricular mass, etc. However, the
      image is very noisy, which renders the delineation of the borders of the left
      ventricle very difficult. While there are many techniques image segmentation,
      this work chooses the artificial neural network (ANN) since it is not very
      sensitive to noise. In order to reduce the processing time, the operator selects
      the region of interest where the neural network will identify the borders.
      Neighborhood and gradient search techniques are then employed to link the points
      and the left ventricle contour is traced. The present method has been efficient
      in detecting the left ventricle borders echocardiography images compared to those
      whose borders were delineated by the specialists. For good results, it is
      important to choose properly the areas to be analyzed and the central points of
      these areas.

PMID- 18626676
TI  - Time domain analysis of the arterial pulse in clinical medicine.
AB  - The arterial pulse at any site is created by an impulse generated by the left
      ventricle as it ejects blood into the aorta, together with multiple impulses
      travelling in the opposite direction from reflecting sites in the peripheral
      circulation. The compound wave at any site depends on the pattern of ventricular
      ejection, the properties of large arteries, particularly their stiffness (which
      determines rate of propagation) and the distance to and impedance mismatch at
      reflecting sites. Physicians are familiar with waveform analysis in the time
      domain, as in the electrocardiogram (ECG) where the principal features are
      explicable on the basis of atrial depolarisation followed by ventricular
      depolarisation, then repolarisation. Effects of cardiac functional and structural
      disease can be inferred from the ECG. It is more difficult to make similar
      interpretations from the pulse waveform and clinicians usually use this only to
      count heart rate, extremes of the pressure pulse to express systolic and
      diastolic pressure, and (sometimes) time from wave foot to incisural notch to
      measure time of systole and diastole. More information can be gleaned from the
      shape of the arterial pressure wave through consideration of the factors which
      create it--on stiffening of large arteries with age, effects of drugs on smallest
      arteries, and changes in such arterial properties on left ventricular load and
      function. Such is a major challenge to future physicians. It is aided by better
      and more accurate methods for measuring flow and diameter as well as pressure
      waveforms, and by appropriate use of other analytic techniques such as analysis
      of the pulse in the frequency domain.

PMID- 18626677
TI  - Validity of accelerometry in assessing the duration of the sit-to-stand movement.
AB  - Accelerometry is frequently used in movement analysis to assess body postures and
      motions. Here, we assessed the validity of ambulatory accelerometric measurement
      of the sit-to-stand (STS) movement duration. We compared accelerometric and opto
      electronic assessment of the STS movement duration under four conditions
      (comfortable, slow, fast movement and exaggerated trunk flexion) with six healthy
      subjects and six subjects with stroke who performed movements six times under
      each condition. Accelerometric and opto-electronic data of STS movement duration
      were strongly related (r = 0.98). Accelerometry showed a fixed bias of 0.07 s
      (95% CI 0.008, 0.141) in healthy subjects and 0.32 s (95% CI 0.223, 0.422) in
      stroke subjects. In healthy subjects, a significant negative proportional bias of
      0.1 was detected (95% CI -0.160, -0.032). Accelerometry showed discriminative
      validity in comparing stroke subjects to healthy subjects, and in comparing speed
      conditions. Our results indicate that accelerometry can provide valid data on the
      STS movement duration, furthermore during its use additional information on the
      STS movement, such as balance control, can be recorded.

PMID- 18626678
TI  - Significance of coprophagy for the fatty acid profile in body tissues of rabbits
      fed different diets.
AB  - Four groups of eight New Zealand hybrid rabbits were fattened with ad libitum
      access to the following pelleted experimental diets: ryegrass meal or alfalfa
      meal fed either alone or with oats meal in a ratio of 1:1. After 25 weeks they
      were slaughtered and dissected. Fatty acid (FA) profiles of caecotrophs (re
      ingested fermentation products of the caecum), perirenal adipose tissue and
      intramuscular fat in the Musculus quadriceps were determined. With high
      proportions of branched-chain FA (BFA) and trans FA, and increased proportions of
      saturated FA relative to the diets, the caecotroph FA profile showed a clear
      fingerprint of anaerobe microbial lipid metabolism including biohydrogenation. By
      contrast, the FA profiles of adipose and lean tissue comprised high proportions
      of polyunsaturated FA (PUFA), whilst BFA and trans FA occurred in much lower
      proportions compared to the caecotrophs. Thus, coprophagy did not substantially
      modify the FA composition of the tissues investigated. Use of forage-only diets,
      compared to the oats supplemented diets, led to extraordinary high proportions of
      n-3 PUFA (including 18:3 and long-chain n-3) in the fat of adipose (21.3 vs.
      6.7%) and lean tissue (15.4 vs. 5.7%). The forage type diet (grass vs. alfalfa)
      had smaller effects on the FA profiles. Indications of diet effects on endogenous
      desaturation, chain elongation and differential distribution of functional FA
      between the two tissues investigated were found.

PMID- 18626679
TI  - Acidosis, oxygen, and interference with mitochondrial permeability transition
      pore formation in the early minutes of reperfusion are critical to
      postconditioning's success.
AB  - Repetitive cycles of reflow/reocclusion in the initial 2 min following release of
      a prolonged coronary occlusion, i.e., ischemic postconditioning (IPoC), salvages
      ischemic myocardium. We have proposed that the intermittent ischemia prevents
      formation of mitochondrial permeability transition pores (MPTP) by maintaining an
      acidic myocardial pH for several minutes until survival kinases can be activated.
      To determine other requisites of IPoC, isolated rabbit hearts were subjected to
      30 min of regional myocardial ischemia and 120 min of reperfusion. Infarct size
      was determined by staining with triphenyltetrazolium chloride. During the first 2
      min of reperfusion the perfusate was either at pH 7.4 following equilibration
      with 95% O(2)/5% CO(2), pH 6.9 following equilibration with 80% N(2)/20% CO(2),
      or pH 7.8 following equilibration with 100% O(2). Whereas acidic, oxygenated
      perfusate for the first 2 min of reperfusion was cardioprotective, protection was
      lost when acidic perfusate was hypoxic. However, the acidic, hypoxic hearts could
      be rescued by addition of phorbol 12-myristate 13-acetate (PMA), a protein kinase
      C (PKC) activator, to the perfusate. Therefore, both low pH and restoration of
      oxygenation are necessary for protection, and the signaling step requiring
      combined oxygen and H(+) must be upstream of PKC. To gain further insight into
      the mechanism of IPoC, the latter was effected with 6 cycles of 10-s
      reperfusion/10-s reocclusion. Its protective effect was abrogated by either
      making the oxygenated perfusate alkaline during the reperfusion phases or making
      the reperfusion buffer hypoxic. Presumably the repeated coronary occlusions
      during IPoC keep myocardial pH low while the resupply of oxygen during the
      intermittent reperfusion provides fuel for the redox signaling that acts to
      prevent MPTP formation even after restoration of normal myocardial pH. Hearts
      treated simultaneously with IPoC and alkaline perfusate could not be rescued by
      addition to the perfusate of either PMA or SB216763 which inhibits GSK-3beta, the
      putative last cytoplasmic signaling step in the signal transduction cascade
      leading to MPTP inhibition. Yet cyclosporin A which also inhibits MPTP formation
      does rescue hearts made alkaline during IPoC. In view of prior studies in which
      the ROS scavenger N-2-mercaptopropionyl glycine aborts IPoC's protection, our
      data reveal that IPoC's reperfusion periods are needed to support redox signaling
      rather than improve metabolism. The low pH, on the other hand, is equally
      necessary and seems to suppress MPTP directly rather than through upstream
      signaling.

PMID- 18626680
TI  - An S-RNase-based gametophytic self-incompatibility system evolved only once in
      eudicots.
AB  - It has been argued that the common ancestor of about 75% of all dicots possessed
      an S-RNase-based gametophytic self-incompatibility (GSI) system. S-RNase genes
      should thus be found in most plant families showing GSI. The S-RNase gene (or a
      duplicate) may also acquire a new function and thus genes belonging to the S
      RNase lineage may also persist in plant families without GSI. Nevertheless,
      sequences that belong to the S-RNase lineage have been found in the Solanaceae,
      Scrophulariaceae, Rosaceae, Cucurbitaceae, and Fabaceae plant families only. Here
      we search for new sequences that may belong to the S-RNase lineage, using both a
      phylogenetic and a much faster and simpler amino acid pattern-based approach. We
      show that the two methods have an apparently similar false-negative rate of
      discovery (approximately 10%). The amino acid pattern-based approach produces
      about 15% false positives. Genes belonging to the S-RNase lineage are found in
      three new plant families, namely, the Rubiaceae, Euphorbiaceae, and Malvaceae.
      Acquisition of a new function by genes belonging to the S-RNase lineage is shown
      to be a frequent event. A putative S-RNase sequence is identified in Lotus, a
      plant genus for which molecular studies on GSI are lacking. The hypothesis of a
      single origin for S-RNase-based GSI (before the split of the Asteridae and
      Rosidae) is further supported by the finding of genes belonging to the S-RNase
      lineage in some of the oldest lineages of the Asteridae and Rosidae, and by
      Baysean constrained tree analyses.

PMID- 18626681
TI  - An early and anaerobic scenario for the transition to undifferentiated
      multicellularity.
AB  - Glycolysis, an ancient energy-processing pathway, can operate either under an
      efficient but slow regime or, alternatively, under a dissipative but fast-working
      regime. Trading an increase in efficiency for a decrease in rate represents a
      cooperative behavior, while a dissipative metabolism can be regarded as a
      cheating strategy. Herein, using irreversible thermodynamic principles and
      methods derived from game theory, we investigate whether, and under what
      conditions, the interplay between these two metabolic strategies may have
      promoted the clustering of undifferentiated cells. In the current model,
      multicellularity implies the loss of motility, which represents a hindrance
      rather than a improvement when competing with mobile single-celled organisms.
      Despite that, when considering glycolysis as the only energy-processing pathway,
      we conclude that cells endowed with a low basal anabolic metabolism may have
      benefited from clustering when faced to compete with cells exhibiting a high
      anabolic activity. The current results suggest that the transition to
      multicellularity may have taken place much earlier than hitherto thought,
      providing support for an extended period of Precambrian metazoan diversification.

PMID- 18626682
TI  - "Rapid two-stage" Norwood operation in a child with multiorgan failure.
AB  - The Norwood I operation continues to be a procedure with significant operative
      mortality. One well-accepted risk factor for death after the first step of the
      Norwood operation is critical preoperative status. We describe herein a new
      concept for the treatment of patients with hypoplastic left heart syndrome (HLHS)
      in very poor preoperative condition. This is a case report of a child who was
      born in a rural hospital. On the second day of life he was referred to our center
      in multiorgan failure. There were signs of liver dysfunction and the child was
      anuric. Therapy was started immediately with prostaglandin and vasodilators as
      well as diuretics, milrinone, and dobutamine. However, systemic perfusion
      continued to be insufficient. Finally, the child was placed on a ventilator. On
      the fourth day of life, bilateral pulmonary artery (PA) banding was performed and
      circulation stabilized immediately. Two hours after the operation urine output
      started. Liver function stabilized over the next couple of days. Two days after
      PA banding the child was weaned from the ventilator. On the 12th day of life a
      Norwood operation with PA debanding and a right ventricle-PA conduit was
      performed, and 2 days postoperatively the child was weaned from the ventilator.
      Twenty days after the operation he was discharged home. When the boy was 4 months
      old a bidirectional cavopulmonary anastomosis was performed. In selected cases of
      patients with HLHS with very poor hemodynamic conditions, a rapid two-stage
      approach with bilateral banding followed by a Norwood operation after cardiac
      stabilization can be recommended.

PMID- 18626683
TI  - Morphologic study of nipple-areola complex in 600 breasts.
AB  - To investigate the morphologic characteristics of the nipple-areola complex, the
      diameter of the nipple-areola complex and the height of the nipple in 300 adult
      women (600 breasts) were measured using micrometer calipers. Furthermore, the
      morphologic characteristics were classified into four types by visual
      observation. Mean diameter of the areola was 4.0 cm, mean diameter of the nipple
      was 1.3 cm, and mean height of the nipple was 0.9 cm. From the morphologic point
      of view, the elevated plateau type without constriction (IIs) was most commonly
      found, being present in 60.2% of breasts. Inverted nipples (III) were found in
      3.5% and unclassified type (IV) such as multiple or divided nipples was found in
      0.3%. Because women have become sensitive about the appearance of their breasts
      and there is increasing cosmetic interest following surgery for breast carcinoma,
      operations on the nipple-areola complex are now common. When a surgeon counsels a
      patient and designs a reconstruction method prior to operation, these data may be
      helpful.

PMID- 18626684
TI  - From forest landscape to agricultural landscape in the developing tropical
      country of Malaysia: pattern, process, and their significance on policy.
AB  - Agricultural expansion and deforestation are spatial processes of land
      transformation that impact on landscape pattern. In peninsular Malaysia, the
      conversion of forested areas into two major cash crops--rubber and oil palm
      plantations--has been identified as driving significant environmental change. To
      date, there has been insufficient literature studying the link between changes in
      landscape patterns and land-related development policies. Therefore, this paper
      examines: (i) the links between development policies and changes in land use/land
      cover and landscape pattern and (ii) the significance and implications of these
      links for future development policies. The objective is to generate insights on
      the changing process of land use/land cover and landscape pattern as a functional
      response to development policies and their consequences for environmental
      conditions. Over the last century, the development of cash crops has changed the
      country from one dominated by natural landscapes to one dominated by agricultural
      landscapes. But the last decade of the century saw urbanization beginning to
      impact significantly. This process aligned with the establishment of various
      development policies, from land development for agriculture between the mid 1950s
      and the 1970s to an emphasis on manufacturing from the 1980s onward. Based on a
      case study in Selangor, peninsular Malaysia, a model of landscape pattern change
      is presented. It contains three stages according to the relative importance of
      rubber (first stage: 1900--1950s), oil palm (second stage: 1960s--1970s), and
      urban (third stage: 1980s--1990s) development that influenced landscape
      fragmentation and heterogeneity. The environmental consequences of this change
      have been depicted through loss of biodiversity, geohazard incidences, and the
      spread of vector-borne diseases. The spatial ecological information can be useful
      to development policy formulation, allowing diagnosis of the country's "health"
      and sustainability. The final section outlines the usefulness of landscape
      analysis in the policy-making process to prevent further fragmentation of the
      landscape and forest loss in Malaysia in the face of rapid economic development.

PMID- 18626685
TI  - Review of agri-environment indexes and stewardship payments.
AB  - Agri-environment programs aim to secure environmental and social stewardship
      services through payments to farmers. A critical component of many agri
      environment programs is an agri-environment index (AEI) used to quantify benefits
      and target investments. An AEI will typically comprise multiple indicators, which
      are weighted and combined using a utility function, to measure the benefit of
      investment options (e.g., projects, farms, regions). This article presents a
      review of AEIs with 11 case studies from agri-environment programs in the United
      States, Australia, and the United Kingdom. We identify a generic procedure used
      to define AEIs and explore the implications of alternative methodological
      approaches. We conclude that AEIs have become an extremely important policy
      instrument and make suggestions for their improvement.

PMID- 18626686
TI  - Characterizing the relative contributions of large vessels to total ocean noise
      fields: a case study using the Gerry E. Studds Stellwagen Bank National Marine
      Sanctuary.
AB  - In 2006, we used the U.S. Coast Guard's Automatic Identification System (AIS) to
      describe patterns of large commercial ship traffic within a U.S. National Marine
      Sanctuary located off the coast of Massachusetts. We found that 541 large
      commercial vessels transited the greater sanctuary 3413 times during the year.
      Cargo ships, tankers, and tug/tows constituted 78% of the vessels and 82% of the
      total transits. Cargo ships, tankers, and cruise ships predominantly used the
      designated Boston Traffic Separation Scheme, while tug/tow traffic was
      concentrated in the western and northern portions of the sanctuary. We combined
      AIS data with low-frequency acoustic data from an array of nine autonomous
      recording units analyzed for 2 months in 2006. Analysis of received sound levels
      (10-1000 Hz, root-mean-square pressure re 1 microPa +/- SE) averaged 119.5 +/-
      0.3 dB at high-traffic locations. High-traffic locations experienced double the
      acoustic power of less trafficked locations for the majority of the time period
      analyzed. Average source level estimates (71-141 Hz, root-mean-square pressure re
      1 microPa +/- SE) for individual vessels ranged from 158 +/- 2 dB (research
      vessel) to 186 +/- 2 dB (oil tanker). Tankers were estimated to contribute 2
      times more acoustic power to the region than cargo ships, and more than 100 times
      more than research vessels. Our results indicate that noise produced by large
      commercial vessels was at levels and within frequencies that warrant concern
      among managers regarding the ability of endangered whales to maintain acoustic
      contact within greater sanctuary waters.

PMID- 18626687
TI  - Testing the hydrological landscape unit classification system and other terrain
      analysis measures for predicting low-flow nitrate and chloride in watersheds.
AB  - Elevated nitrate concentrations in streamwater are a major environmental
      management problem. While land use exerts a large control on stream nitrate,
      hydrology often plays an equally important role. To date, predictions of low-flow
      nitrate in ungauged watersheds have been poor because of the difficulty in
      describing the uniqueness of watershed hydrology over large areas. Clearly,
      hydrologic response varies depending on the states and stocks of water, flow
      pathways, and residence times. How to capture the dominant hydrological controls
      that combine with land use to define streamwater nitrate concentration is a major
      research challenge. This paper tests the new Hydrologic Landscape Regions (HLRs)
      watershed classification scheme of Wolock and others (Environmental Management
      34:S71-S88, 2004) to address the question: Can HLRs be used as a way to predict
      low-flow nitrate? We also test a number of other indexes including inverse
      distance weighting of land use and the well-known topographic index (TI) to
      address the question: How do other terrain and land use measures compare to HLR
      in terms of their ability to predict low-flow nitrate concentration? We test this
      for 76 watersheds in western Oregon using the U.S. Environmental Protection
      Agency's Environmental Monitoring and Assessment Program and Regional
      Environmental Monitoring and Assessment Program data. We found that HLRs did not
      significantly improve nitrate predictions beyond the standard TI and land-use
      metrics. Using TI and inverse-distance weighting did not improve nitrate
      predictions; the best models were the percentage land use-elevation models. We
      did, however, see an improvement of chloride predictions using HLRs, TI, and
      inverse-distance weighting; adding HLRs and TI significantly improved model
      predictions and the best models used inverse-distance weighting and elevation.
      One interesting result of this study is elevation consistently predicted nitrate
      better than TI or the hydrologic classification scheme.

PMID- 18626688
TI  - Integrating conservation and development at the National Marine Park of
      Alonissos, Northern Sporades, Greece: perception and practice.
AB  - Available information on the socioeconomic implications of marine protected areas
      (MPAs) for the socioculturally diverse Mediterranean region is scant. The
      National Marine Park of Alonissos, Northern Sporades (NMPANS), Greece was
      established in 1992 as a foundation for the conservation of the endangered
      Mediterranean monk seal Monachus monachus. The evolution of the degree of
      acceptance of and satisfaction from the NMPANS by involved stakeholder groups
      (fishermen, tourism operators, hoteliers and owners of rooms to let, governmental
      bodies, nongovernmental bodies, students, domestic and foreign tourists) were
      investigated 13 years after its establishment using written questionnaires
      delivered during personal interviews. The initial positive attitude of local
      professionals for the NMPANS has eroded due to the unsatisfactory fulfillment of
      expectations for socioeconomic development. Fishermen expressed dissatisfaction
      with, mistrust toward, and a reluctancy to communicate with the NMPANS's
      management body. They believe that the fishery areas have decreased in actual
      geographic area because of the prohibitive measures; fish stocks are declining;
      compensation for damage to fishery equipment by the Mediterranean monk seal and
      for the prohibitive measures should be provided; and stricter enforcement of
      regulations should take place. On the other hand, tourism operators, who organize
      trips for tourists to the NMPANS, unanimously reported direct economic benefits.
      Furthermore, there was a disparity in the perception of socioeconomic benefits
      derived from the NMPANS between governmental bodies and local stakeholders. The
      governmental bodies and the nongovernmental organization MOm-Hellenic Society for
      the Study and Protection of the Monk Seal postulated that there had been
      considerable socioeconomic benefits for the local community of Alonissos due to
      the establishment of the NMPANS, whereas the local nongovernmental organization
      Ecological and Cultural Movement of Alonissos claimed benefits were scant.
      Tourists (domestic and foreign) believe that the NMPANS is not the main
      attraction to Alonissos Island but is part of a composite, including serenity,
      aesthetic beauty, and small-scale tourism development, which can turn Alonissos
      Island into an ideal eco-tourism destination; a common aspiration for both the
      tourists and the local community by general consensus. The aim of the NMPANS to
      integrate conservation and development lies in (1) the effectiveness of the
      NMPANS management body in formulating a strategic management plan that would
      accommodate stakeholders' interests and aspirations and (2) a national policy of
      conservation and enhancement of natural resources with consistency and
      continuity. Quantitative assessment of the socioeconomic effectiveness of the
      Mediterranean MPAs using a common methodology would facilitate the identification
      of intraregional variation and better planning for the network of MPAs in the
      Mediterranean.

PMID- 18626689
TI  - Use of descriptors of ecosystem functioning for monitoring a national park
      network: a remote sensing approach.
AB  - Baseline assessments and monitoring of protected areas are essential for making
      management decisions, evaluating the effectiveness of management practices, and
      tracking the effects of global changes. For these purposes, the analysis of
      functional attributes of ecosystems (i.e., different aspects of the exchange of
      matter and energy) has advantages over the traditional use of structural
      attributes, like a quicker response to disturbances and the fact that they are
      easily monitored through remote sensing. In this study, we described the
      spatiotemporal patterns of different aspects of the ecosystem functioning of the
      Spanish national parks and their response to environmental changes between 1982
      and 2006. To do so, we used the NOAA/AVHRR-GIMMS dataset of the Normalized
      Difference Vegetation Index (NDVI), a linear estimator of the fraction of
      photosynthetic active radiation intercepted by vegetation, which is the main
      control of carbon gains. Nearly all parks have significantly changed during the
      last 25 years: The radiation interception has increased, the contrast between the
      growing and nongrowing seasons has diminished, and the dates of maximum and
      minimum interception have advanced. Some parks concentrated more changes than
      others and the degree of change varied depending on their different environmental
      conditions, management, and conservation histories. Our approach identified
      reference conditions and temporal changes for different aspects of ecosystem
      functioning, which can be used for management purposes of protected areas in
      response to global changes.

PMID- 18626690
TI  - Predictors of technical skill acquisition among resident trainees in a
      laparoscopic skills education program.

PMID- 18626691
TI  - Effect of ferric iron on siderophore production and pyrene degradation by
      Pseudomonas fluorescens 29L.
AB  - The effect of ferric iron [Fe(III)] on pyrene degradation and siderophore
      production was studied in Pseudomonas fluorescens 29L. In the presence of 0.5
      microM of Fe(III) and 50 mg of pyrene per liter of medium as a carbon source, 2.2
      mg of pyrene was degraded per liter of medium per day and 25.3 microM of 2,3-DHBA
      (2,3-dihydroxybenzoic acid) equivalent of siderophores was produced per day.
      However, the pyrene degradation rate was 1.3 times higher and no siderophores
      were produced with the addition of 1 microM of Fe(III). Similar trends were seen
      with 50 mg of succinate per liter of medium as a carbon source, although the
      growth of strain 29L and the succinate degradation rate were higher. In the
      absence of siderophore production, pyrene and succinate continued to be
      biodegraded. This indicates that Fe(III) and not siderophore production affects
      the hydrocarbon degradation rate. Only 18% of strain 29L mutants capable of
      growth on pyrene produced siderophores, while among the mutants capable of growth
      on succinate, only 10% produced siderophores. This indicates that siderophores
      are not required for pyrene biodegradation. Fe(III) enhances pyrene degradation
      in Pseudomonas fluorescens 29L but it may be utilized by mechanisms other than
      siderophores.

PMID- 18626692
TI  - PCR detection of Serratia spp. using primers targeting pfs and luxS genes
      involved in AI-2-dependent quorum sensing.
AB  - Quorum sensing is the ability of bacteria to communicate and coordinate behavior
      emitting signaling molecules. A series of primers for PCR detection of Serratia
      spp. has been designed using as targets the pfs and luxS genes involved in AI-2
      dependent quorum sensing. The identities of the PCR products (193 and 102 bp)
      were confirmed by commercial sequencing. Twenty-seven Serratia strains
      (representing 10 different species) tested positive for the presence of the pfs
      and luxS genes, while a total of 7 different species of non-Serratia (25 strains)
      were tested and gave negative results. The sensitivity and specificity of the pfs
      and luxS-based PCR assay were also checked in artificially contaminated
      bacterial samples. In this study we established a novel method to detect Serratia
      using quorum-sensing genes as diagnostic markers.

PMID- 18626693
TI  - Targeted mutagenesis at charged residues in Bacillus sphaericus BinA toxin
      affects mosquito-larvicidal activity.
AB  - The mosquito-larvicidal binary toxin from Bacillus sphaericus is composed of two
      polypeptides called BinA and BinB with molecular masses of approximately 42 and
      51 kDa. Both components are required for full activity, with BinB acting as a
      specificity determinant and BinA being responsible for toxic action. To
      investigate the role of the selected charged residues in BinA, four mutants were
      generated by replacing charged amino acids with alanine (R97A, E98A, R101A, and
      E114A). All mutant proteins were produced at high levels and formed inclusion
      bodies similar to that of the wild type. Mosquito-larvicidal assays against Culex
      quinquefasciatus larvae revealed that the mutant R97A completely lost its
      activity and mutants E98A, R101A, and E114A showed significantly reduced
      toxicity. Intrinsic fluorescence spectroscopy analysis indicated that alanine
      substitutions at these positions did not alter the overall structure of the
      toxin. Binding of the mutants to BinB was not different from that of the wild
      type, suggesting that these mutations did not affect BinA-BinB interaction.
      Results demonstrated that R97, E98, R101, and E114 neither play a direct role in
      maintenance of BinA structure nor are involved in BinA-BinB interaction. Since
      these residues are required for full activity, they may play an important role
      during toxin internalization and/or toxic action of BinA inside the target cells.

PMID- 18626694
TI  - Isolation and symbiotic characteristics of two Tn5-derived phage-resistant
      Bradyrhizobium japonicum strains that nodulate soybean.
AB  - Using transponson Tn5 mutagenesis, two transconjugants of Bradyrhizobium
      japonicum with the properties of both phage resistance and ability to induce
      nodulation were isolated at the frequency of 0.02%. These transconjugants were
      tested for their symbiotic performance on soybean cv. JS335 under greenhouse and
      field conditions. Both phage-resistant mutants induced nodules (nod (+)), but the
      transconjugant B. japonicum E13 was ineffective in nitrogen fixation (fix (-)).
      Rhizobiophage presence in the inoculum of phage-resistant mutants did not
      influence the symbiotic effectiveness. The mixture of wild strain and phage in
      the inoculum caused reduced symbiotic performance under controlled conditions,
      while under a field environment phage (100 and 500 mul of approximately 10(8)
      particles ml(-1)) presence did not have any recognizable effect on increased
      nodule dry weight, nitrogenase activity, or foliar N(2) content. On the basis of
      restriction fragment length polymorphism analysis, phage-sensitive, less
      effective, homologous bradyrhizobia belonging to B. japonicum were detected in
      root nodules of both inoculated and uninoculated plants. Inoculation of a higher
      concentration of phage in the inoculum significantly reduced the symbiotic
      performance, while the lower concentration of phage did not show any effect on
      phage-susceptible, less effective, homologous bradyrhizobia or, thus, symbiotic
      efficiency under field conditions. The phage-resistant mutant B. japonicum A49
      showed effective symbiosis as efficient as that of the wild strain. Inoculation
      of phage-resistant mutants with lytic phage may reduce the occupancy of phage
      susceptible, ineffective/less effective/mediocre homologous bradyrhizobia strains
      under natural complex soil conditions.

PMID- 18626695
TI  - Changes in arterial oxygen saturation (SaO(2)) before, during, and after meals in
      stroke patients in a rehabilitation setting.
AB  - The aim of this study was to investigate the changes in arterial oxygen
      saturation (SaO(2)) of stroke patients during mealtime and whether duration of
      feeding (time to finish a meal) and mode of feeding (self-feed versus being fed)
      were associated with such changes. This study also investigated whether the
      consequence of aspiration pneumonia in the stroke patients was associated with
      SaO(2) drops during mealtime. The findings of this study showed that stroke
      patients but not the controls had a small but significant SaO(2) drop during
      meals (0.91%, IQR = 1.53%, p < 0.05 in being fed; 1.04%, IQR = 1.35%, p = 0.013,
      in self-feed). Duration of feeding and mode of feeding, however, did not have an
      association with mealtime SaO(2) changes. The SaO(2) drop during mealtime was not
      an early indicator of aspiration pneumonia.

PMID- 18626696
TI  - Esophageal adenocarcinoma: pseudo-nutcracker esophagus.
AB  - Pseudoachalasia due to adenocarcinoma is well known. We report a case of
      nutcracker esophagus in the setting of outflow obstruction from esophageal
      adenocarcinoma. Endoscopy is warranted to exclude similar lesions in patients
      with "pseudo-nutcracker esophagus".

PMID- 18626697
TI  - Cross-cultural adaptation and validation of the Dutch version of SWAL-QoL.
AB  - The aim of this work was to translate the 44-item SWAL-QoL into Dutch (SWAL-QoL
      NL) and compare the validity of this questionnaire against Euroqol in a Dutch
      population with dysphagia. SWAL-QoL was translated according to international
      guidelines. SWAL-QoL-NL and Euroqol were completed by 152 patients in seven
      diagnosis groups. Internal consistency and correlations were calculated. Scores
      for nine subscales (General burden, Food selection, Eating duration, Fear of
      eating, Sleep, Fatigue, Mental health, Social functioning and a symptom score)
      ranged between 0.80 and 0.92 (Cronbach's alpha). Two subscales (Eating desire and
      Communication scored 0.67 and 0.60, respectively, and were removed from the
      questionnaire. The 14-item battery on clinical symptoms showed an internal
      consistency of 0.80, allowing the use of a sum score on group level in clinical
      research. Correlation of SWAL-QoL-NL subscales with the Euroqol was negligible to
      low (Pearson's correlations range = 0.09-0.36). The 39-item SWAL-QoL-NL proved to
      be a reliable tool to examine the impact of dysphagia on quality of life in a
      Dutch population. Internal consistency allows the use of nine subscales of SWAL
      QoL-NL for comparisons on a group level (0.80 < alpha < 0.92) only. Also a
      Symptom score can be derived from the raw data.

PMID- 18626698
TI  - Multimedia article. Thoracoscopic patch repair of a right-sided congenital
      diaphragmatic hernia in a neonate.
AB  - PURPOSE: Minimally invasive techniques continue to expand in pediatric surgery;
      however, there has been some debate over the appropriate operative technique for
      the management of congenital diaphragmatic hernias in neonates. We present a
      video of a thoracoscopic patch repair of a right-sided Bochdalek congenital
      diaphragmatic hernia (CDH) in a 3-day-old male. METHODS: Our patient was noted to
      have a right-sided CDH on chest X-ray following respiratory distress at the time
      of birth. The patient's remaining neonatal workup also confirmed hypoplastic
      transverse aortic arch with coarctation, ventricular septal defect (VSD), and
      patent ductus arteriosus, which were initially diagnosed by prenatal ultrasound.
      After monitoring the patient for hemodynamic stability and discussion with the
      family and involved pediatric cardiothoracic surgeons, the decision was made to
      proceed with a thoracoscopic repair of the CDH. RESULTS: The large right-sided
      CDH was noted to involve herniated small bowel, colon, and liver. The
      diaphragmatic defect was successfully repaired thoracoscopically using a 5 x 5 cm
      polytetrafluoroethylene (PTFE) patch. The patient was extubated on the second
      postoperative day and ultimately underwent aortic arch augmentation, VSD closure,
      and patent ductus arteriosus ligation and division at 1 month of age. There has
      been no evidence of CDH recurrence in follow-up. CONCLUSIONS: As demonstrated by
      our video, large right-sided congenital diaphragmatic hernias requiring patch
      repair can be successfully repaired thoracoscopically with appropriate surgeon
      comfort and experience. This minimally invasive approach may also be used in
      neonates with associated cardiac defects with appropriate cardiothoracic surgical
      consultation and support. To our knowledge this is the first reported case of a
      thoracoscopic repair of a Bochdalek (posterolateral) hernia with a prosthetic
      patch in a neonate with significant congenital cardiac anomalies.

PMID- 18626699
TI  - Evaluation of lightweight titanium-coated polypropylene mesh (TiMesh) for
      laparoscopic repair of large hiatal hernias.
AB  - BACKGROUND: The use of mesh for laparoscopic repair of large hiatal hernias may
      reduce recurrence rates in comparison with primary suture repair. However, there
      is a potential risk of mesh-related oesophageal complications due to prosthesis
      erosion. The aim of this study was to evaluate a lightweight polypropylene mesh
      (TiMesh) repair of hiatal hernias with particular reference to intraluminal
      erosion. METHODS: Data were collected prospectively on 18 consecutive patients
      undergoing elective laparoscopic repair of a large hiatal hernia with the use of
      TiMesh between November 2004 and December 2005. Quality of life and symptom
      analysis was performed using QOLRAD questionnaires preoperatively and
      postoperatively after 6 weeks, 6 months, 1 year and 2 years. Barium studies were
      performed preoperatively and 2 years postoperatively to assess hernia recurrence.
      After 2 years, oesophagogastric endoscopy was performed to assess signs of mesh
      related complications. RESULTS: All operations were completed laparoscopically.
      There was no 30-day mortality and median hospital stay was 2.8 days (range 2-13
      days). Complications occurred in two patients (11%), both of whom were treated
      without residual disability. Two years after hiatal hernia repair, there was
      significant improvement in quality-of-life scores (QOLRAD 5.79, p < 0.001). There
      was no difference between pre- and postoperative dysphagia scores. No signs of
      stricture formation or prosthetic erosion were identified during endoscopic
      follow-up. One patient had a small (2 cm) sliding hiatal hernia demonstrated by
      barium studies, which was asymptomatic. CONCLUSIONS: Laparoscopic reinforcement
      of primary hiatal closure with TiMesh leads to a durable repair in patients with
      large hiatal hernias. Endoscopic follow-up did not show any signs of mesh-related
      complications after prosthetic reinforcement of the crural repair. Our
      preliminary results suggest that it is safe to proceed with this lightweight
      polypropylene mesh for reinforcement of the hiatal repair.

PMID- 18626700
TI  - Comparison of oncological outcomes after laparoscopic transhiatal and open
      esophagectomy for T1 esophageal adenocarcinoma.
AB  - INTRODUCTION: This study compared pathological characteristics and patterns of
      disease recurrence for patients with pT1 esophageal adenocarcinoma treated with
      either laparoscopic transhiatal esophagectomy or open esophagectomy. METHODS:
      From January 2000-December 2006, 44 patients had pT1 esophageal adenocarcinoma
      after esophagectomy. No patients had neoadjuvant treatment. Twenty-four patients
      had an Ivor Lewis operation, 4 had an open transhiatal and 16 had a laparoscopic
      transhiatal operation. RESULTS: There were 37 men. The median age was 64 years
      (range 35-80 years). Median lymph node yield was 19 (10-51) after an Ivor Lewis
      operation, 16 (3-28) after an open transhiatal operation and 15 (4-41) after a
      laparoscopic transhiatal operation. There were two in-hospital deaths (5%), both
      following open Ivor Lewis operation. All patients in the laparoscopic group had
      N0 disease; none received adjuvant treatment. Two patients (7%) in the open group
      had N1 disease, of whom one patient received adjuvant chemotherapy. Eleven
      patients had submucosal invasion. Alive patients had median follow-up of 36
      months (range 5-87 months). One patient in the laparoscopic group had recurrence
      at 22 months. This patient had poorly differentiated N0 disease which was limited
      to the mucosa and died at 24 months. Two patients in the open group developed
      recurrence, at 6 months (N0 disease with submucosal invasion) and 8 months (N1
      disease with submucosal invasion) and died at 7 and 14 months, respectively. Both
      patients had poorly differentiated tumours. The second patient with N1 disease is
      alive and well at 14 months. Estimated survival (Kaplan-Meier) at 3 years was
      93%. CONCLUSIONS: As compared with open transthoracic esophagectomy, there is no
      oncological detriment in the treatment of pT1 esophageal adenocarcinoma by
      laparoscopic transhiatal esophagectomy. The incidence of recurrence is small (7%)
      but can occur even in patients with tumour limited to the mucosa or N0 disease.

PMID- 18626701
TI  - Robotic implantation of gastric electrical stimulation electrodes for
      gastroparesis.
AB  - BACKGROUND: Gastric electrical stimulation (GES) is a low-morbidity treatment
      option that may be effective for refractory symptoms in patients with
      gastroparesis of diabetic or idiopathic etiology. During surgery to initiate GES,
      two electrodes are tunneled in the gastric antrum in a precise location. If these
      electrodes pass through the mucosa and into the gastric lumen (determined by
      endoscopy) they must be repositioned, often multiple times. During this
      procedure, extensive suturing to anchor the electrodes is necessary once properly
      placed. Robotic surgical systems may provide surgeons with several technical and
      ergonomic advantages during this procedure when compared with a standard
      laparoscopic approach. METHODS: Over a 26-month period, 22 GES systems were
      implanted. The initial procedures were performed laparoscopically. After the
      first 15 laparoscopic cases, a technique for robotically implanting leads was
      developed and employed for the remainder of the series. Demographics, operative
      time, and endoscopically confirmed electrode mucosal perforations were quantified
      and compared based on operative approach. RESULTS: Patients were similar
      demographically. Total operative time did not differ based on technique (152 +/-
      40 min laparoscopic versus 158 +/- 38 min robotic placement; p = 0.6). Mucosal
      perforations on first attempt at electrode placement occurred more frequently
      with the laparoscopic than with the robotic technique (15/30 laparoscopic versus
      1/14 robotic; p = 0.006). There were no procedure-related complications.
      CONCLUSIONS: The robotic approach to GES electrode implantation is feasible and
      safe. Compared with standard laparoscopic techniques, the accurate insertion and
      anchoring of these leads can be accomplished more efficiently and comfortably
      using robotic techniques. Whether robotic GES electrode placement will result in
      significant clinical advantages for patients will require long-term follow-up.

PMID- 18626702
TI  - Factors influencing the rising rates of adrenal surgery: analysis of a 25-year
      experience.
AB  - BACKGROUND: Adrenal surgery has been radically changed by laparoscopy and it is
      reasonable to wonder whether the increase in the number of adrenalectomies is
      entirely justified. There is still debate on the transperitoneal versus the
      retroperitoneal approach, the advantages and drawbacks of which are discussed
      here. METHODS: Between 1983 and 2007, we performed 279 adrenalectomies in 264
      consecutive patients, divided into two groups: before and after the advent of
      laparoscopic adrenalectomy (LA). We analyzed the factors that increased the
      number of adrenalectomies in recent years. The LAs were further divided into
      three consecutive periods and the morbidity and conversion rates, and mean
      operating times were compared. RESULTS: More procedures were performed after the
      advent of LA, i.e., 55 (19.7%) beforehand versus 224 (80.3%) afterwards,
      irrespective of the type of disease, for instance: incidentaloma, 17.6% versus
      82.4% (p ? 0.0001); pheochromocytoma, 20.7% versus 79.3% (p?0.0001); Conn's
      disease, 19.8% versus 80.2% (p ? 0.0001); Cushing's disease, 17.2% versus 82.8%
      (p?0.0001); cortical carcinoma, 30% versus 70% (p?0.001). Analyzing the three LA
      periods, operating times were the only statistically significant variable
      (p?0.0001). CONCLUSIONS: The progressive increase in the number of
      adrenalectomies performed is due more to a better understanding of adrenal
      disease than to the availability of minimally invasive techniques. The choice of
      a laparoscopic approach (trans- or retroperitoneal) should depend on the
      surgeon's experience.

PMID- 18626703
TI  - Three simple steps during closed laparoscopic entry may minimize major injuries.
AB  - OBJECTIVES: To describe three steps: (1) the initial Veress pressure (VIP
      Pressure), (2) transient high-pressure pneumoperitoneum (HIP-Entry) prior to
      trocar/cannula insertion, and (3) visual entry with a trocarless cannula during
      closed laparoscopic entry, which may reduce major injuries. DESIGN: Prospective
      observational cohort study (Canadian Task Force Classification II-2). SETTING:
      University-affiliated teaching hospital. INTERVENTIONS: VIP-Pressure. During
      laparoscopic entry, the initial VIP pressure was measured and correlated against
      the body habitus and parity of 365 consecutive women. HIP-Entry was performed in
      2,498 consecutive cases. In 100 women, the CO(2) volume, heart rate, blood
      pressure, oxygen saturation, and pulmonary compliance were recorded at pressures
      of 10, 15, 20, 25, and 30 mmHg. Visual entry with a trocarless blunt cannula was
      performed in 776 women. The cannula, housing a 0 degrees laparoscope, was rotated
      clockwise applying minimal downward force. MEASUREMENTS AND RESULTS: VIP
      Pressure. Pneumoperitoneum was established after one, two or three Veress needle
      attempts at the umbilicus in 82.4%, 10.9%, and 4.0% of women, respectively. In
      seven (2.2%), pneumoperitoneum was established at the left upper quadrant (LUQ)
      during the fourth attempt, and in two (0.6%) entry was abandoned. Median initial
      Veress pressure was 4 mmHg (range 2-10 mmHg). The VIP pressure correlated
      positively with women's weight (r = 0.518, p < 0.001) and body mass index (BMI)
      (r=0.545, p<0.001), and negatively with parity (r= -0.179, p<0.001). HIP-Entry.
      The abdomen was insufflated to 25-30 mmHg prior to primary trocar/cannula
      insertion. There were no changes in cardiovascular parameters between 15 and 30
      mmHg. A 21% decrease in pulmonary compliance from 15 to 30 mmHg was of no
      clinical significance. No injury has been experienced with the visual cannula in
      776 cases. CONCLUSIONS: (1) A VIP-Pressure (<10 mmHg) indicates intraperitoneal
      placement of the Veress needle. (2) The use of transient HIP-Entry does not
      adversely affect cardiopulmonary function in healthy women. (3) Visual cannula
      offers an additional step towards safer entry.

PMID- 18626704
TI  - Laparoscopic resection for endoscopically unresectable colorectal polyps:
      analysis of 525 patients.
AB  - BACKGROUND: For the management of endoscopically irretrievable polyps, several
      minimally invasive procedures are currently available as alternatives to
      conventional laparotomy. However, the high rate of malignant transformation
      despite initially benign histology continues to be a problem. METHODS: Within the
      framework of a prospective multicenter observational study, all patients with
      adenomatous polyps unsuitable for endoscopic removal and with benign histology
      were investigated. In addition to an analysis of the perioperative course and the
      definitive histology, the overall and disease-free survival rates of patients
      with malignant transformation of colorectal adenomas were also calculated.
      RESULTS: A total of 525 patients (median age 65.3 years; median body mass index
      25.6 kg/m(2)) underwent a laparoscopic resection. Conversion to laparotomy became
      necessary in 17 (3.2%) cases. The perioperative morbidity rate was 20.8%, and
      malignant transformation occurred in a total of 18.1% of the adenomatous polyps.
      The median number of lymph nodes removed was 12, and lymph node metastases were
      seen in a total of 14.8% of the patients (T1--4.8%, T2--19.4%, T3--25%, T4-
      100%). Estimated 5-year overall and disease-free survival rates were 92.4% and
      80.6%, respectively. CONCLUSIONS: For the management of endoscopically
      unresectable polyps, laparoscopic resection is currently the technique of choice.
      In addition to the benefits of minimally invasive surgery, in the hands of an
      experienced surgeon it achieves results comparable with those of open surgery. In
      view of the high rate of malignant transformation and the absence of unequivocal
      factors predictive of already present malignant transformation, an oncologically
      radical operation is essential. In the elderly patient presenting with
      comorbidities limited resection aiming to minimize surgical trauma in potentially
      benign disease may be considered. In such a case, however, frozen-section
      histology is obligatory.

PMID- 18626705
TI  - Camera navigation and tissue manipulation; are these laparoscopic skills related?
AB  - BACKGROUND: It is a tacit assumption that clinically based expertise in
      laparoscopic tissue manipulation entails skilfulness in angled laparoscope
      navigation. The main objective of this study was to investigate the relation
      between these skills. To this end, face and construct validity had to be
      established for the place arrow (PA) and camera navigation (CN) tasks on the
      SimSurgery SEP. METHODS: Thirty-three novices (no laparoscopy experience) and 33
      experienced participants (>50 laparoscopic procedures and familiar with angled
      laparoscopy) performed both tasks twice, on one of two hardware platforms
      (SimSurgery SimPack or Xitact/Mentice IHP), and rated the realism and didactic
      value of SimSurgery SEP on five-point scales. RESULTS: Both tasks were rated by
      the experienced participants as realistic (CN: 3.7; PA: 4.1) and SimSurgery SEP
      as a user-friendly environment to train basic skills (4.1). Both tasks were
      performed in less time by the experienced group, with shorter tip trajectories.
      For both groups jointly, the time to accomplish each task correlated with the tip
      trajectory and also with the time and tip trajectories of the opposite task
      (Spearman's correlation, p <or= 0.05). Within the groups however, the
      performances on both tasks did not always correlate. CONCLUSIONS: A correlation
      was not always found between the performances on the two tasks, which suggests
      that clinically based expertise in tissue manipulation does not automatically
      entail skilfulness in angled laparoscope navigation, and vice versa. Training and
      assessment of basic laparoscopic skills should focus on these tasks
      independently. More research is needed to better identify the skills and required
      proficiency levels for different laparoscopic tasks.

PMID- 18626706
TI  - "Peek port": a novel approach for avoiding conversion in laparoscopic colectomy.
AB  - BACKGROUND: This study aimed to assess the efficacy of a method for avoiding
      conversion to laparotomy in patients considered for laparoscopic colectomy.
      Patients deemed to be at high risk for conversion to laparotomy were initially
      approached via an 8-cm midline incision ("peek port") with the laparoscopic
      equipment unopened. If intraperitoneal conditions were favorable, the procedure
      was performed using hand-assisted laparoscopy. If intraperitoneal conditions were
      unfavorable, the incision was extended to a formal laparotomy. Patients deemed to
      be at low risk for conversion to laparotomy were approached laparoscopically from
      the outset. METHODS: Data from 241 consecutive patients brought to the operating
      room for intended laparoscopic colectomy were retrieved from a prospective
      database. RESULTS: The study population consisted of 132 men and 109 women with a
      mean age of 62 years and a mean body mass index (BMI) of 28. Prior abdominal
      surgery had been performed in 49% of these patients. Inflammatory conditions
      accounted for 38% of the diagnoses, and enteric fistulas were present in 7% of
      the cases. Of the 25 patients who underwent the initial "peek port," 8 (32%)
      underwent immediate incision extension to formal laparotomy. Hand-assisted
      laparoscopic colectomy was performed in 17 (68%) of these 25 patients, with one
      subsequent conversion to formal laparotomy. Of the 216 patients initially
      approached laparoscopically, 5 (2%) required conversion to laparotomy. The
      laparotomy rate for the "peek port" group (9/25, 36%) was higher than for the
      initial laparoscopy group (5/216, 2%) (p < 0.0001). Of the 233 patients from both
      groups who underwent laparoscopy, the overall rate for conversion to laparotomy
      was 3% (6/233). CONCLUSIONS: The "peek port" approach to the patient with a
      potentially hostile abdomen allows for rapid assessment of intraperitoneal
      conditions and is associated with an overall low rate of conversion from
      laparoscopy to laparotomy. This technique should reduce overall cost by avoiding
      the use of laparoscopic equipment as well as potential complications related to
      trocar placement and laparoscopic dissection in patients who will ultimately
      require formal laparotomy.

PMID- 18626707
TI  - Preoperative administration of controlled-release oxycodone as a transition
      opioid for total intravenous anaesthesia in pain control after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: The complexity of pain from laparoscopic cholecystectomy and the need
      for treating incident pain provide rationale for multipharmacological analgesia.
      We investigated the preoperative administration of controlled-release (CR)
      oxycodone as transition opioid from remifentanil infusion for pain after
      laparoscopic cholecystectomy. METHODS: Fifty consecutive patients undergoing
      laparoscopic cholecystectomy were randomly, double-blindly assigned to treatment
      group (n=25, CR oxycodone: 1 h before surgery and 12 h after the first
      administration) or to the control group (n=25, placebo: administered at the same
      intervals). General anaesthesia was maintained with propofol and remifentanil
      target-controlled infusions (TCIs). All patients received ketorolac 30 mg i.v.
      Tramadol i.v. was administered for patient-controlled analgesia (PCA)
      postoperatively. Numerical rating scale for pain at rest and at movement (NRSr
      and NRSi), tramadol consumption, times to readiness to surgery and awakening,
      times to modified Aldrete's and modified Post-Anesthetic Discharge Scoring System
      (PADSS)>9 and side effects were evaluated. RESULTS: All NRSr and NRSi and
      tramadol consumption were significantly lower in the treatment group. The
      oxycodone group showed higher modified Aldrete's scores at each time and reached
      a PADSS>9 faster. Side effects and postoperative nausea and vomiting episodes
      were comparable. CONCLUSIONS: We demonstrated the success of a
      multipharmacological treatment including opioid premedication with CR oxycodone
      used as transition opioid for TCI remifentanil infusion; the treatment group
      showed lower pain scores and rescue analgesic consumption, shorter time to
      discharge from recovery room and from surgical ward, and the same incidence of
      side effects, comparably to controls.

PMID- 18626708
TI  - Factors associated with ostomy reversal.
AB  - BACKGROUND: The natural history of colostomies and ileostomies for colonic
      disease is not well described. This study aimed to identify factors that have an
      impact on colostomy and ileostomy reversal among patients with colonic diseases.
      METHODS: A retrospective review of patients with ileostomies and colostomies was
      performed at a university hospital from 1999 to 2005. Demographic, operative, and
      outcome data were collected. Data were analyzed using analysis of variance
      (ANOVA), t-test, and descriptive statistics. Mantel-Haenstel chi-square was used
      to establish association (p<0.05). RESULTS: There were 96 patients (49 women)
      with an overall mean age of 56 years at the time of ostomy creation. Ostomy
      reversal was performed for 35 patients after an average interval of 5.6 months
      (range, 12-432 days). The patients' ages were significantly different between the
      reversed and nonreversed groups (p=0.01). The mean age was 49.9 years for the
      reversed group and 60.5 years for the nonreversed group. In a logistic regression
      model including demographic variables, African Americans were four times less
      likely to undergo reversal than Caucasians [odds ratio (OR), 0.24; 95% confidence
      interval (CI), 0.075-0.794]. Loop ileostomies (p=0.05) and sigmoid colostomies
      (p=0.01) were the only types of ostomies that demonstrated a significant
      association with reversal. Loop ileostomy was five times more likely to be
      reversed than sigmoid colostomy (OR, 0.17; 95% CI, 0.049-0.595). CONCLUSIONS:
      Colostomy or ileostomy creation is a basic skill in the armamentarium of the
      general surgeon for treating complex diseases of the colon. Age, race, and type
      of ostomy creation are significant predictors for reversal. This data may be
      useful for consulting patients preoperatively regarding postoperative
      expectations.

PMID- 18626709
TI  - Characterization of antifungal chitinase from marine Streptomyces sp. DA11
      associated with South China Sea sponge Craniella australiensis.
AB  - The gene cloning, purification, properties, kinetics, and antifungal activity of
      chitinase from marine Streptomyces sp. DA11 associated with South China sponge
      Craniella australiensis were investigated. Alignment analysis of the amino acid
      sequence deduced from the cloned conserved 451 bp DNA sequence shows the
      chitinase belongs to ChiC type with 80% similarity to chitinase C precursor from
      Streptomyces peucetius. Through purification by 80% ammonium sulfate, affinity
      binding to chitin and diethylaminoethyl-cellulose anion-exchange chromatography,
      6.15-fold total purification with a specific activity of 2.95 Umg(-1) was
      achieved. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      showed a molecular weight of approximately 34 kDa and antifungal activities were
      observed against Aspergillus niger and Candida albicans. The optimal pH,
      temperature, and salinity for chitinase activity were 8.0, 50 degrees C, and 45 g
      per thousand psu, respectively, which may contribute to special application of
      this marine microbe-derived chitinase compared with terrestrial chitinases. The
      chitinase activity was increased by Mn(2+), Cu(2+), and Mg(2+), while strongly
      inhibited by Fe(2+) and Ba(2+). Meanwhile, SDS, ethyleneglycoltetraacetic acid,
      urea, and ethylenediaminetetraacetic acid were found to have significantly
      inhibitory effect on chitinase activity. With colloidal chitin as substrates
      instead of powder chitin, higher V (max) (0.82 mg product/min.mg protein) and
      lower K (m) (0.019 mg/ml) values were achieved. The sponge's microbial symbiont
      with chitinase activity may contribute to chitin degradation and antifungal
      defense. To our knowledge, it was the first time to study sponge-associated
      microbial chitinase.

PMID- 18626711
TI  - Perineal stapled prolapse resection: a new procedure for external rectal
      prolapse.
AB  - PURPOSE: A perineal approach to treating rectal prolapse is ideal for frail
      patients. Recently, internal rectal redundancy has been successfully treated with
      transanal resection using the Contour Transtar stapler. This technique has been
      modified to the perineal stapled prolapse resection. The surgical technique and
      the preliminary results of the new procedure for external rectal prolapse are
      presented. METHODS: Patients not suited for transabdominal treatment were
      included prospectively for perineal stapled prolapse resection in two colorectal
      centers. Feasibility, complications, and reinterventions were assessed. RESULTS:
      In 14 of 15 patients, perineal stapled prolapse resection was performed without
      complications in a median operating time of 33 (range, 22-52) minutes. One
      procedure was changed to an Altemeier because of a staple line disruption. Two
      patients required reintervention as a result of postoperative hemorrhage. No
      other severe complications occurred. At follow-up, all patients were well and
      showed no early recurrence of prolapse. CONCLUSIONS: Perineal stapled prolapse
      resection is a new surgical procedure for external rectal prolapse, which is easy
      and quick to perform. Functional results and long-term recurrence rate must be
      investigated further.

PMID- 18626710
TI  - A new prokaryotic farnesyldiphosphate synthase from the octocoral Eunicea fusca:
      differential display, inverse PCR, cloning, and characterization.
AB  - We recently reported that the biosynthesis of fuscol, a diterpene from the
      octocoral Eunicea fusca, is inducible by the application of plant signaling
      factors such as salicylic acid to the coral's algal symbiont. In this study, an
      mRNA differential display approach has been employed with the dinoflagellate
      symbiont of this octocoral which has led to the isolation of a
      farnesyldiphosphate synthase (FPPS) that was transcriptionally activated under
      conditions that led to an induction of fuscol biosynthesis. Using a degenerate
      primer based on the aspartate-rich motifs found in prenylsynthases and a cassette
      ligation strategy, we report the cloning of the complete FPPS associated with the
      E. fusca dinoflagellate symbiont Symbiodinium sp. The protein exhibited the
      enzymatic properties associated with FPPS, namely, the synthesis of farnesyl
      diphosphate from geranyldiphosphate and isopentenyl diphosphate. The amino acid
      sequence of this FPPS has a high sequence similarity (82%) to known archaeal
      isoprenyl diphosphate synthases. This is the first description of a prokaryotic
      FPPS derived from a marine source.

PMID- 18626712
TI  - Persistent perineal sinus after ileoanal pouch excision in inflammatory bowel
      diseases: incidence, risk factors, and clinical course.
AB  - PURPOSE: This study was designed to determine the incidence of persistent
      perineal sinus after pouch excision in inflammatory bowel disease, risk factors,
      and long-term clinical course. METHODS: The study included 35 consecutive
      patients who underwent pouch excision at St. Mark's Hospital, London, between
      1996 and 2006. Incidence of persistent perineal sinus and its long-term clinical
      course were reported. Sixteen variables were analyzed to determine their
      association with persistent perineal sinus. RESULTS: There were 17 men and 18
      women with median age of 37 (range, 20-57) years. The final diagnosis was
      ulcerative colitis in 28 and Crohn's disease in 7 patients. The indications for
      pouch excision included pelvic or perineal sepsis in 60 percent, pouchitis in 23
      percent, and poor pouch function in 17 percent. Persistent perineal sinus was
      diagnosed in 14 patients (40 percent). Pouch excision for fistula or abscess in
      the pelvis or perineum (odds ratio, 8; 95 percent confidence interval, 1.4-45.5)
      was an independent predictor for persistent perineal sinus. Twenty-six procedures
      were performed in patients with persistent perineal sinus and resulted in healing
      in 64 percent. Curettage was the most common procedure used. CONCLUSIONS: Pouch
      excision for pelvic or perineal sepsis was an independent predictor for
      persistent perineal sinus.

PMID- 18626713
TI  - The occlusive tourniquet: a simple method for rectal stump washout during open
      and laparoscopic surgery.
AB  - Rectal stump washout with cytolytic agents is recommended and usually performed
      during anterior rectal or rectosigmoid resection. The use of a linear stapler
      instrument during ultralow anterior resection makes the placement of pelvic
      clamps difficult for rectal stump washout prior to resection. The objective of
      this work is to demonstrate the use of a simple procedure, the occlusive
      tourniquet for rectal stump washout. Occlusive tourniquet applied to open
      technique: after complete dissection of the rectum and sigmoid colon according to
      the usual technique, a simple piece of tubing from an intravenous line is passed
      behind and around the rectum/sigmoid colon at some point distal to the tumor to
      form an occlusive tourniquet. Occlusive tourniquet applied to laparoscopic
      technique: similar to the open technique, tubing is passed through the left iliac
      fossa trocar and passed behind the sigmoid mesocolon. This simple procedure
      allows easy exposure and dissection of the mesorectum, without traumatizing the
      rectum/sigmoid colon or the tumor and lavage can be performed without the need
      for clamps or other instruments which may traumatize the rectum and provoke
      anastomotic failure. In conclusion, the occlusive tourniquet is a simple method
      for rectal stump washout so this step can be done.

PMID- 18626714
TI  - Multimedia article. Standardized hand-assisted laparoscopic right colectomy.

PMID- 18626715
TI  - Long-term functional outcome and risk factors for recurrence after surgical
      treatment for low and high perianal fistulas of cryptoglandular origin.
AB  - PURPOSE: This study assessed long-term functional outcome and explored risk
      factors for fistula recurrence in patients surgically treated for cryptoglandular
      fistulas. METHODS: Three hundred ten consecutive patients were surgically treated
      for perianal fistulas. After exclusion of patients with inflammatory bowel
      disease or HIV, 179 patients remained. Patients were divided into two groups:
      those who received fistulotomy for low perianal fistulas and those who received
      rectal advancement flap for high perianal fistulas. Time to fistula recurrence
      was the main outcome and Cox proportional hazard models were used to assess the
      importance of various risk factors. Functional outcome was assessed using the
      Vaizey and colorectal functional outcome (COREFO) questionnaires. RESULTS: The
      median follow-up duration was 76 months (range, 7-134). The 3-year recurrence
      rate for low perianal fistulas treated by fistulotomy (n = 109) was 7 percent (95
      percent confidence interval, 1-13 percent). In high transsphincteric fistulas
      treated by rectal advancement flap (n = 70), the recurrence rate was 21 percent
      (95 percent confidence interval, 9-33 percent). In both groups, soiling was
      reported at 40 percent. None of the seven potential risk factors examined were
      statistically significant. CONCLUSIONS: Fistula recurrence rate after fistulotomy
      was low. No clear risk factors were found. Overall functional outcome in terms of
      continence was good. However, a substantial amount of patients reported soiling.

PMID- 18626716
TI  - Design and validation of a comprehensive fecal incontinence questionnaire.
AB  - PURPOSE: Fecal incontinence can have a profound effect on quality of life. Its
      prevalence remains uncertain because of stigma, lack of consistent definition,
      and dearth of validated measures. This study was designed to develop a valid
      clinical and epidemiologic questionnaire, building on current literature and
      expertise. METHODS: Patients and experts undertook face validity testing.
      Construct validity, criterion validity, and test-retest reliability was
      undertaken. Construct validity comprised factor analysis and internal consistency
      of the quality of life scale. The validity of known groups was tested against 77
      control subjects by using regression models. Questionnaire results were compared
      with a stool diary for criterion validity. Test-retest reliability was calculated
      from repeated questionnaire completion. RESULTS: The questionnaire achieved good
      face validity. It was completed by 104 patients. The quality of life scale had
      four underlying traits (factor analysis) and high internal consistency (overall
      Cronbach alpha = 0.97). Patients and control subjects answered the questionnaire
      significantly differently (P < 0.01) in known-groups validity testing. Criterion
      validity assessment found mean differences close to zero. Median reliability for
      the whole questionnaire was 0.79 (range, 0.35-1). CONCLUSIONS: This questionnaire
      compares favorably with other available instruments, although the interpretation
      of stool consistency requires further research. Its sensitivity to treatment
      still needs to be investigated.

PMID- 18626717
TI  - Soybean (Glycine max) root lignification induced by ferulic acid. The possible
      mode of action.
AB  - Ferulic acid, in the form of feruloyl CoA, occupies a central position as an
      intermediate in the phenylpropanoid pathway. Due to the allelopathic function,
      its effects were tested on root growth, H(2)O(2) and lignin contents, and
      activities of cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) and peroxidase
      (POD, EC 1.11.1.7) from soybean (Glycine max (L.) Merr.) root seedlings. Three
      day-old seedlings were cultivated in half-strength Hoagland's solution (pH 6.0),
      with or without 1.0 mM ferulic acid in a growth chamber (25 degrees C, 12/12 hr
      light/dark photoperiod, irradiance of 280 micromol m(-2) s(-1)) for 24 or 48 hr.
      Exogenously supplied ferulic acid induced premature cessation of root growth,
      with disintegration of the root cap, compression of cells in the quiescent
      center, increase of the vascular cylinder diameter, and earlier lignification of
      the metaxylem. Moreover, the allelochemical decreased CAD activity and H(2)O(2)
      level and increased the anionic isoform PODa5 activity and lignin content. The
      lignin monomer composition of ferulic acid-exposed roots revealed a significant
      increase of guaiacyl (G) units. When applied jointly with piperonylic acid (an
      inhibitor of the cinnamate 4-hydroxylase, C4H), ferulic acid increased lignin
      content. By contrast, the application of 3,4-(methylenedioxy) cinnamic acid (an
      inhibitor of the 4-coumarate:CoA ligase, 4CL) with ferulic acid did not. Taken
      together, these results suggest that ferulic acid may be channeled into the
      phenylpropanoid pathway (by the 4CL reaction) and, further, may increase the
      lignin monomer amount solidifying the cell wall and restricting the root growth.

PMID- 18626719
TI  - The role of health-related quality of life outcomes in clinical decision making
      in surgery for esophageal cancer: a systematic review.
AB  - BACKGROUND: Esophagectomy for cancer offers a chance of cure but is associated
      with morbidity, at least a temporary reduction in health-related quality of life
      (HRQL), and a 5-year survival of approximately 30%. This research evaluated how
      and whether HRQL outcomes contribute to surgical decision making. METHODS: A
      systematic review identified randomized trials and longitudinal and cross
      sectional studies that assessed HRQL after esophagectomy with multidimensional
      validated questionnaires. Articles were independently evaluated by two reviewers,
      and the value of HRQL in clinical decision making was categorized in three ways:
      (1) the assessment of the quality of HRQL methodology according to predefined
      criteria; (2) the influence of HRQL outcomes on treatment recommendations and/or
      informed consent; and (3) the HRQL after esophagectomy for cancer in
      methodologically robust studies. RESULTS: Eighteen publications were identified,
      of which 16 (89%) were categorized as having robust HRQL design. Of these
      studies, 3 concluded that HRQL influenced treatment recommendations and 11
      (including the former 3) informed patient consent. The remaining five papers were
      well designed, but the authors did not use HRQL to influence treatment
      recommendations or informed consent. After esophagectomy, patients report major
      deterioration in most aspects of HRQL with slow recovery. CONCLUSION: HRQL
      outcomes are relevant to surgical decision making. Methods to communicate HRQL
      outcomes to patients are required to inform consent and clinical practice.

PMID- 18626720
TI  - A presidential blueprint for success and change.

PMID- 18626721
TI  - Do micromorphometric features of metastatic deposits within sentinel nodes
      predict nonsentinel lymph node involvement in melanoma?
AB  - INTRODUCTION: Multiple attempts have been made to identify melanoma patients with
      a positive sentinel lymph node (SLN) who are unlikely to harbor residual disease
      in the nonsentinel lymph nodes (NSLN). We examined whether the size and location
      of the metastases within the SLN may help further stratify the risk of additional
      positive NSLN. METHODS: A review of our Institutional Review Board (IRB)-approved
      melanoma database was undertaken to identify all SLN positive patients with SLN
      micromorphometric features. Univariate logistic regression techniques were used
      to assess potential significant associations. Decision tree analysis was used to
      identify which features best predicted patients at low risk for harboring
      additional disease. RESULTS: The likelihood of finding additional disease on
      completion lymph node dissection was significantly associated with primary
      location on the head and neck or lower extremity (P = 0.01), Breslow thickness >4
      mm (P = 0.001), the presence of angiolymphatic invasion (P < 0.0001),
      satellitosis (P = 0.004), extranodal extension (P = 0.0002), three or more
      positive SLN (P = 0.02) and tumor burden within the SLN >1% surface area (P =
      0.004). Sex, age, mitotic rate, ulceration, Clark level, histologic subtype,
      regression, and number of SLN removed had no association with finding a positive
      NSLN. Location of the metastases (capsular, subcapsular or parenchymal) showed no
      correlation with a positive NSLN. Decision tree analysis incorporating size of
      the metastatic burden within the SLN along with Breslow thickness can identify
      melanoma patients with a positive SLN who have a very low risk of harboring
      additional disease with the NSLN. CONCLUSION: Size of the metastatic burden
      within the SLN, measured as a percentage of the surface area, helps stratify the
      risk of harboring residual disease in the nonsentinel lymph nodes (NSLN), and may
      allow for selective completion lymphadenectomy.

PMID- 18626722
TI  - Quality of care for cardiovascular disease-related conditions in patients with
      and without mental disorders.
AB  - OBJECTIVE: We compared the quality of care for cardiovascular disease (CVD)
      related risk factors for patients diagnosed with and without mental disorders.
      METHODS: We identified all patients included in the fiscal year 2005 (FY05) VA
      External Peer Review Program's (EPRP) national random sample of chart reviews for
      assessing quality of care for CVD-related conditions. Using the VA's National
      Psychosis Registry and the National Registry for Depression, we assessed whether
      patients had received diagnoses of serious mental illness (schizophrenia, bipolar
      disorder, or other psychoses) or depression during FY05. Using multivariable
      logistic regression and generalized estimating equation analyses, we assessed
      patient and facility factors associated with receipt of guideline concordant care
      for hypertension (total N = 24,016), hyperlipidemia (N = 46,430), and diabetes (N
      = 10,943). RESULTS: Overall, 70% had good blood pressure control, 90% received a
      cholesterol (hyperlipidemia) screen, 77% received a retinal exam for diabetes,
      and 63% received recommended renal tests for diabetes. After adjustment, compared
      to patients without SMI or depression, patients with SMI were less likely to be
      assessed for CVD risk factors, notably hyperlipidemia (OR = 0.58; p < 0.001), and
      less likely to receive recommended follow-up assessments for diabetes: foot exam
      (OR = 0.68; p < 0.001), retinal exam (OR = 0.65; p < 0.001), or renal testing (OR
      = 0.64; p < 0.001). Patients with depression were also significantly less likely
      to receive adequate quality of care compared to non-psychiatric patients,
      although effects were smaller than those observed for patients with SMI.
      CONCLUSIONS: Quality of care for major chronic conditions associated with
      premature CVD-related mortality is suboptimal for VA patients with SMI,
      especially for procedures requiring care by a specialist.

PMID- 18626723
TI  - The closure of a medical practice forces older patients to make difficult
      decisions: a qualitative study of a natural experiment.
AB  - OBJECTIVE: The closure of a primary care practice and the relocation of the
      physicians and staff to a new office forced patients to decide whether to follow
      their primary care physicians (PCP) or to transfer their care elsewhere. This
      study explores the perspectives of the older patients affected by this change.
      DESIGN: Qualitative study. SETTING AND PARTICIPANTS: Two lists of patients older
      than 60 years from the original office were generated: (1) those who had followed
      their PCPs to the further practice and (2) those who chose new PCPs at an
      affiliated nearby clinic. One hundred forty patients from each of the two lists
      were randomly selected for study. MEASUREMENT: Eight months after the clinic's
      closure, patients responded to an open-ended question asking patients to describe
      the transition. Using content analysis, two investigators independently coded all
      of the written responses. RESULTS: Over 85% of patients in both groups had been
      with their original PCP for longer than 2 years. Patients that elected to
      transition their care to a new PCP within their community were older (75 vs 70
      years) and more likely to be living alone (38% vs 18%), both p < 0.01. There was
      still considerable frustration associated with the clinic's closure. Patients
      from both groups had variable levels of satisfaction with their new primary care
      arrangements. Patients who moved to the near clinic, now seeing a new physician,
      commented on being satisfied with the proximity of the site. On the other hand,
      these patients also expressed longing for the previous arrangement (the building,
      the staff, and especially their prior physician). Patients who transferred their
      care to the further clinic indicated a profound loyalty to their PCP and an
      appreciation of the added features at the new site. Yet, many patients still
      described being upset with the difficulties associated with the further distance.
      CONCLUSION: The closing of this practice was difficult for this cohort of older
      patients. Patients' decisions were considerably influenced by whether they
      imagined that convenience or their established relationship with their PCP was of
      a higher priority to them.

PMID- 18626724
TI  - Musculoskeletal training for orthopaedists and nonorthopaedists: experiences in
      Nepal.
AB  - Orthopaedic surgical training in Nepal began in 1998, and four major centers now
      produce between 15 and 20 graduates annually. The duration of the training is
      four years in one center and three years in the remaining centers. Trainees have
      adequate trauma exposure. The major challenges include: tailoring training to
      suit local needs, avoiding the dangers of market driven orthopaedic surgery,
      adequately emphasizing and implementing time honored methods of closed fracture
      treatment, and ensuring uniformity of exposure to the various musculoskeletal
      problems. Training in research methods needs to be implemented more effectively.
      The evaluation process needs to be more uniform and all training programs need to
      complement one another and avoid unhealthy competition. Training for
      nonorthopaedists providing musculoskeletal care is virtually nonexistent in
      Nepal. Medical graduates have scant exposure to trauma and musculoskeletal
      diseases during their training. General surgeons provide the majority of trauma
      care and in the rural areas, health assistants, auxiliary health workers and
      physiotherapy assistants provide much needed basic services, but all lack formal
      training. Traditional "bone setters" in Nepal often cater to certain faithful
      clientele with sprains, minor fractures etc. A large vacuum exists in Nepal for
      trained nonorthopaedists leading to deficiencies in prehospital care, safe
      transport and basic, primary emergency care. The great challenges are yet to be
      addressed.

PMID- 18626725
TI  - Three new olefinic acetogenin glycosides from leaves of Staphylea bumalda DC.
AB  - Three new olefinic acetogenin glycosides (3, 6 and 7) have been isolated from
      Staphylea bumalda DC., together with four known congeners (1, 2 and 4, 5). Their
      structures were determined on the bases of spectral data.

PMID- 18626726
TI  - Inhibitory effect of the extracts from Thai medicinal plants on iNOS expression
      in mouse macrophage RAW 264.7.
AB  - In the present study, we screened the inhibitory effect of the extract from 50
      Thai medicinal plants on an inducible-nitric oxide synthase (iNOS) expression
      induced by lipopolysaccharide (LPS) in mouse macrophages RAW 264.7. From this
      screening, the extracts of root bark of Clausena guillauminii, C. lunulata, and
      C. excavata (Rutaceae) were found as the extracts which showed potent inhibitory
      effect on the iNOS protein expression in concentration-dependent manner.
      Furthermore, hydrophobic active components may exist in C. guillauminii.

PMID- 18626727
TI  - Simultaneous detection of JAK2 V617F mutation and Bcr-Abl translocation in a
      patient with chronic myelogenous leukemia.

PMID- 18626728
TI  - Successful treatment of acquired amegakaryocytic thrombocytopenic purpura
      refractory to corticosteroids and intravenous immunoglobulin with antithymocyte
      globulin and cyclosporin.
AB  - Four patients with acquired amegakaryocytic thrombocytopenic purpura, who had
      failed corticosteroids, intravenous immunoglobulin and cyclophosphamide therapy,
      were treated with antithymocyte globulin, followed by cyclosporin. Three patients
      achieved complete remission in 28-178 days and the response duration was 16-60
      months from the beginning of treatment. One patient achieved a partial response
      for 2 months followed by myelodysplastic syndrome 5 months later. He died in 9
      months due to intracerebral bleeding. Marrow cytogenetics showed 47, XY, +21.

PMID- 18626729
TI  - Three-dimensional virtual images modify the waveform of pupillary near response.
AB  - PURPOSE: To investigate the effects of the continuous viewing of horizontal
      disparities on the pupillary near response by using three-dimensional (3-D)
      displays. METHODS: The pupillary diameter and the horizontal eye position of both
      eyes were measured during the near response in eight healthy young adults. The
      measurements were made before and after viewing a 3-D movie for 15 or 30 min, or
      a two-dimensional (2-D) movie for 90 min. The near response was elicited by a
      real target that moved from the far position (0.5 m) to the near position (0.1 or
      0.125 m) in the midsagittal plane at a constant velocity of +/- 0.26 diopters
      (D)/s. The accommodative demand was 6 or 8 D. RESULTS: A delay in the pupillary
      dilation in the near response was observed immediately after a 30-min viewing of
      a 3-D movie with an accommodative demand of 8 D (P < 0.01, one-way analysis of
      variance, Dunnett's multiple comparison test). The delay in the pupillary
      dilation was not observed after a 90-min viewing of a 2-D movie. CONCLUSIONS:
      Continuous viewing of horizontal disparities can induce a delay in the pupillary
      dilation in the near response. The parameters of the pupillary near response are
      useful in assessing the effects of 3-D viewing.

PMID- 18626730
TI  - Proteomic analysis of rat retina in a steroid-induced ocular hypertension model:
      potential vulnerability to oxidative stress.
AB  - PURPOSE: To investigate global protein expression profiles in the retinas of
      normal and glucocorticoid-induced ocular hypertensive rats by proteomic analysis.
      METHODS: Ocular hypertension was induced by topical application of dexamethasone
      (DEX) for 4 weeks. Age-matched untreated rats served as controls. Intraocular
      pressure (IOP) was monitored by an electronic tonometer. Retinal protein
      expression profiling was carried out by two-dimensional fluorescence difference
      gel electrophoresis (2-D DIGE). Proteins were identified by matrix-assisted laser
      desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS: In
      DEX-treated rats, average IOP was elevated significantly compared with controls.
      With DEX treatment, levels of four proteins were altered, as revealed by 2-D DIGE
      and MALDI-TOF mass spectrometry: apolipoprotein A1 (apoA1), a lipid-binding
      protein, upregulated 1.9-fold, P < 0.05; alpha A crystallin (CRYAA), a molecular
      chaperone, downregulated 2.7-fold, P < 0.01; superoxide dismutase 1 (SOD1), an
      antioxidant enzyme, downregulated 2.3-fold, P < 0.05; and triosephosphate
      isomerase 1 (TPI1), a glycolytic enzyme, downregulated 2.3-fold, P < 0.01.
      CONCLUSIONS: Downregulation of CRYAA, SOD1, and TPI1, observed here after a short
      period of DEX-induced ocular hypertension, may be involved in the onset of neural
      damage in steroid-induced glaucoma.

PMID- 18626731
TI  - Inhibition of choroidal neovascularization by blocking vascular endothelial
      growth factor receptor tyrosine kinase.
AB  - PURPOSE: To investigate the role played by receptors of vascular endothelial
      growth factors, Flt-1 and KDR/Flk-1, on an experimental model of choroidal
      neovascularization (CNV). METHODS: The vascular endothelial growth factor-A (VEGF
      A) receptor-specific tyrosine kinase inhibitor SU5416 was administered to a laser
      induced mouse model of CNV. The formation of CNV and the degree of vascular
      permeability in Flt-1 tyrosine kinase domain-deficient mice were also
      investigated. RESULTS: SU5416 reduced vascularity and vascular endothelial cell
      proliferation, and promoted endothelial cell apoptosis within CNV. Furthermore,
      the formation of CNV and the degree of vascular permeability were significantly
      reduced in Flt-1 tyrosine kinase domain-deficient mice, and this effect was
      enhanced by the administration of SU5416. CONCLUSIONS: Both Flt-1 and KDR/Flk-1
      have a significant role in CNV formation. Suppression of apoptosis may be
      involved in the process.

PMID- 18626732
TI  - Photodynamic therapy with verteporfin in Japanese patients with subfoveal
      choroidal neovascularization secondary to age-related macular degeneration (AMD):
      results of the Japanese AMD Trial (JAT) extension.
AB  - PURPOSE: To evaluate the longer term safety of verteporfin therapy in Japanese
      patients with subfoveal classic choroidal neovascularization (CNV) due to age
      related macular degeneration (AMD). METHODS: Patients completing 12 months of the
      Japanese AMD Trial (JAT) were eligible to enter the extension phase if the
      investigator judged they would potentially benefit from further verteporfin
      therapy. Patients had follow-up visits every 3 months, receiving verteporfin
      therapy in the study eye if leakage from CNV was observed on fluorescein
      angiography. Mean change from baseline in best-corrected visual acuity was a
      safety variable in the extension. RESULTS: Of the 51 patients entering the study
      extension, 46 (90%) completed 24 months. Adverse events were similar to those in
      the first 12 months of JAT; no cumulative toxic effect of verteporfin therapy was
      identified. Mean visual acuity letter score in the study eye increased from 50.8
      (20/100(+1) at baseline to 54.0 (20/80(-1)) at month 24. At month 24, six
      patients (13%) had lost 15 or more letters of visual acuity, of whom four (9%)
      had lost 30 or more letters. CONCLUSION: Verteporfin therapy was shown to be safe
      and effective through 24 months in Japanese patients with subfoveal CNV due to
      AMD, supporting its long-term use in these patients.

PMID- 18626733
TI  - Photodynamic therapy for polypoidal choroidal vasculopathy: vaso-occlusive effect
      on the branching vascular network and origin of recurrence.
AB  - PURPOSE: To determine whether photodynamic therapy (PDT) has a vaso-occlusive
      effect on the branching vascular network in polypoidal choroidal vasculopathy
      (PCV) and whether PDT can prevent future recurrence. METHODS: We analyzed pre-and
      post-PDT indocyanine green angiography (ICGA) results of 27 patients (27 eyes)
      who were diagnosed with PCV and who had shown clinical improvement accompanied by
      occlusion of polypoidal lesions after PDT. We also investigated the recurrent
      events in these patients and the origin of the recurrences. RESULTS: The
      branching vascular network persisted, at least in part, in 20 (87%) of 23 eyes
      undergoing one PDT session and in two (50%) of four eyes undergoing two PDT
      sessions. In the remaining five eyes, we could not determine definitively whether
      the branching vessels were occluded completely. Recurrent serous changes occurred
      in nine eyes (33%) 14-48 months after the last PDT. ICGA revealed that these
      changes were caused by new polypoidal lesions that originated from further-grown
      branches of the persistent branching vascular network. Diffuse leakage from
      undetermined sources seemed to coexist in two eyes. CONCLUSIONS: PDT cannot
      induce complete occlusion of the branching vascular network. PDT does not prevent
      future recurrence, because new active polypoidal lesions may develop from the
      persistent branching vessels in the network.

PMID- 18626734
TI  - Polypoidal choroidal vasculopathy with drusen.
AB  - PURPOSE: To study the prevalence and clinical features of drusen in eyes with
      polypoidal choroidal vasculopathy (PCV). METHODS: Retrospectively, we reviewed
      the records of 98 consecutive patients with PCV (102 eyes). Drusen were examined
      in the inner macula, which was defined as an area within 1500 microm of the
      center of the fovea. Eyes that had at least one intermediate or large (>or=63
      microm) soft drusen within the inner macula were defined as having drusen.
      RESULTS: In these 102 eyes with PCV, 23 (23%) showed soft drusen in the inner
      macula. In such cases, the fellow eyes, those without a PCV lesion, sometimes
      also showed soft drusen in the inner macula (11 eyes); 34 (33%) of the eyes with
      PCV had soft drusen in the inner macula of at least one eye. Comparison of the
      group of eyes with PCV and drusen in one or both eyes with the group with PCV and
      no drusen in either eye revealed no significant difference in patient
      characteristics or in ocular manifestations. CONCLUSIONS: Drusen are not an
      unusual feature of PCV, at least in Japanese patients, and, when present, they
      appear to have only a minor effect, if any, on the clinical course.

PMID- 18626735
TI  - Efficacy and retention times of intravitreal triamcinolone acetonide for macular
      edema.
AB  - PURPOSE: To evaluate the retention of intravitreal triamcinolone acetonide (TA)
      particles and the efficacy of TA therapy for patients with cystoid macular edema
      in branch retinal vein occlusion (BRVO) or diabetic macular edema (DME). We
      monitored the TA particles until absorption from the vitreous cavity was
      complete. The correlation between the intravitreal retention time of TA and its
      efficacy was evaluated based on central macular thickness (CMT). RESULTS: The
      intravitreal TA retention time was a mean 141.8 +/- 139.6 days in BRVO patients
      and 114.5 +/- 59.6 days in DME patients. Patient age and retention time were
      negatively correlated (r = -0.46; P = 0.013). At 6 months posttreatment the mean
      CMT decreased from 544.1 +/- 143.7 to 322.4 +/- 131.9 mum in BRVO patients and
      from 454.5 +/- 119.0 to 371.2 +/- 209.4 mum in DME patients. Retention time and
      CMT reduction were positively correlated in BRVO patient (r = 0.56, P = 0.02) but
      not in DME patients (P = 0.06). CONCLUSIONS: Intravitreal TA reduced the CMT in
      BRVO and DME patients over 6 months. The retention time was longer in younger
      individuals. The efficacy of the therapy depended on the intravitreal TA
      retention time observed clinically in BRVO patients. Biomicroscopic examination
      of intravitreal TA is useful for evaluation of its efficacy.

PMID- 18626737
TI  - Lacrimal sac vascular leiomyoma.

PMID- 18626736
TI  - Case of bilateral multiple herpetic epithelial keratitis manifested as dendriform
      epithelial edema during primary Kaposi's varicelliform eruption.
AB  - BACKGROUND: Bilateral herpetic keratitis has been reported in patients with
      atopy, measles, graft-versus-host disease, and altered immune status. We report a
      serologically verified case of primary, simultaneous onset, bilateral, atypical
      epithelial herpetic keratitis that manifested as dendriform epithelial edema
      during a generalized dermatitis incident. CASE: A 37-year-old man with chronic
      atopic dermatitis developed Kaposi's varicelliform eruption and bilateral
      dendritic epithelial keratitis with corneal epithelial edema. OBSERVATIONS: The
      pathogens isolated from both eyes were identified as herpes simplex virus type 1
      (HSV-1) by a direct immunofluorescence method. Serological tests obtained on
      three different occasions over a 5-week period verified a primary HSV infection.
      CONCLUSIONS: With serological verification, we report a rare case of primary,
      simultaneous onset, bilateral, dendritic epithelial keratitis at a very early
      stage with complications of generalized herpetic disease in a patient with atopic
      dermatitis.

PMID- 18626738
TI  - A case of Vibrio vulnificus keratitis.

PMID- 18626739
TI  - Management of Candida albicans donor-to-host transmission following penetrating
      keratoplasty.

PMID- 18626740
TI  - Significant intraocular lens folding due to severe capsular contraction.

PMID- 18626741
TI  - A high viral load of Epstein-Barr virus DNA in ocular fluids in an HLA-B27
      negative acute anterior uveitis patient with psoriasis.

PMID- 18626742
TI  - Pigment epithelial changes with abnormal fundus autofluorescence after
      photodynamic therapy for idiopathic choroidal neovascularization.

PMID- 18626743
TI  - Delayed exudative subfoveal retinal detachment following successful macular hole
      surgery.

PMID- 18626744
TI  - Choroidal folds and retinal pigment epithelium tear following intravitreal
      bevacizumab injection for exudative age-related macular degeneration.

PMID- 18626745
TI  - Congenital simple hamartoma of the retinal pigment epithelium in an Asian.

PMID- 18626746
TI  - A structural insight into CK2 inhibition.
AB  - The acidophilic Ser/Thr protein kinase CK2 displays some unique properties such
      as high pleiotropicity and constitutive activity. CK2 is involved in many
      fundamental aspects of the normal cell life, for instance it promotes cell
      survival and enhances the tumour phenotype under special circumstances. This
      makes CK2 an appealing target for the development of inhibitors with
      pharmacological potential. Here we present an overview of our recent studies on
      inhibitors directed to the CK2 ATP-binding site whose distinctive features are
      highlighted by the ability to use both ATP and GTP as co-substrates and by its
      low susceptibility to staurosporine inhibition. We discuss the effects of the
      binding of different chemical families of fairly selective inhibitors with
      potency in the nanomolar or low micromolar range. An important common energetic
      contribution to the binding is due to the hydrophobic interaction with the apolar
      surface region of the CK2 binding cleft. The analysis of the known CK2 crystal
      structures reveals the presence of some highly conserved water molecules in this
      region. These waters reside near Lys68, in an area with a positive electrostatic
      potential that is able to attract and orient negatively charged ligands. The
      presence of this positive region and of two unique bulky residues, Ile66 and
      Ile174, responsible for the reduced dimension of the CK2 active site, play a
      critical role in determining ligand orientation and binding selectivity.

PMID- 18626747
TI  - Comparison of mesenchymal stem cell and osteosarcoma cell adhesion to
      hydroxyapatite.
AB  - Immortalized cells are often used to model the behavior of osteogenic cells on
      orthopaedic and dental biomaterials. In the current study we compared the
      adhesive behavior of two osteosarcoma cell lines, MG-63 and Saos-2, with that of
      mesenchymal stem cells (MSCs) on hydroxyapatite (HA). It was found that
      osteosarcoma cells demonstrated maximal binding to fibronectin-coated HA, while
      MSCs alternately preferred HA coated with collagen-I. Interesting, the binding of
      MG-63 and Saos-2 cells to fibronectin was mediated by both alpha5 and alphav
      containing integrin heterodimers, whereas only alphav integrins were used by
      MSCs. Cell spreading was also markedly different for the three cell types.
      Osteosarcoma cells exhibited optimal spreading on fibronectin, but poor spreading
      on HA disks coated with fetal bovine serum. In contrast, MSCs spread very well on
      serum-coated surfaces, but less extensively on fibronectin. Finally, we evaluated
      integrin expression and found that MSCs have higher levels of alpha2 integrin
      subunits relative to MG-63 or Saos-2 cells, which may explain the enhanced
      adhesion of MSCs on collagen-coated HA. Collectively our results suggest that
      osteosarcoma cells utilize different mechanisms than MSCs during initial
      attachment to protein-coated HA, thereby calling into question the suitability of
      these cell lines as in vitro models for cell/biomaterial interactions.

PMID- 18626748
TI  - Effect of filler size and shape on local nanoindentation modulus of resin
      composites.
AB  - The aim of this study was to determine the Young's moduli (E) of a series of
      model dental resin-composites using nanoindentation, and to examine how E was
      influenced by differences in filler-size and shape. Materials with different
      filler-sizes and shapes but constant filler volume-fraction were investigated.
      Disc specimens, mounted in polystyrene resin were mechanically polished and
      tested with a nanoindenter. One-way ANOVA and Bonferroni test were used for the
      statistical analysis. Regression analysis was used to investigate the correlation
      between E and filler-size. E ranged from 9.31 to 12.54 GPa for spherical fillers
      and from 14.09 to 17.03 GPa for irregular fillers. Statistically significant
      differences were found among the groups. Strong quadratic correlations were
      observed between E and filler-size for unimodal materials with spherical and
      irregular fillers, but were not statistically significant. Filler-size and shape
      seemed to be fine-tuning factors for E.

PMID- 18626749
TI  - Antibacterial coatings for medical devices based on glass polyalkenoate cement
      chemistry.
AB  - A biofilm is an accumulation of micro-organisms and their extracellular products
      forming a structured community on a surface. Biofilm formation on medical devices
      has severe health consequences as bacteria growing in this lifestyle are tolerant
      to both host defense mechanisms and antibiotic therapies. However, silver and
      zinc ions inhibit the attachment and proliferation of immature biofilms. The
      objective of this study is to evaluate whether it is possible to produce silver
      and zinc-containing glass polyalkenoate cement (GPC) coatings for medical devices
      that have antibacterial activity and which may therefore inhibit biofilm
      formation on a material surface. Two silver and zinc-containing GPC coatings (A
      and B) were synthesised and coated onto Ti6Al4V discs. Their handling properties
      were characterised and atomic absorption spectrometery was employed to determine
      zinc and silver ion release with coating maturation up to 30 days. The
      antibacterial properties of the coatings were also evaluated against
      Staphylococcus aureus and a clinical isolate of Pseudomonas aeruginosa using an
      agar diffusion assay method. The majority of the zinc and silver ions were
      released within the first 24 h; both coatings exhibited antibacterial effect
      against the two bacterial strains, but the effect was more intense for B which
      contained more silver and less zinc than A. Both coatings produced clear zones of
      inhibition with each of the two organisms tested. In this assay, Ps. aeruginosa
      was more sensitive than S. aureus. The diameters of these zones were reduced
      after the coating had been immersed in water for varying periods due to the
      resultant effect on ion release.

PMID- 18626750
TI  - Injectable iron-modified apatitic bone cement intended for kyphoplasty:
      cytocompatibility study.
AB  - In this study, the cytocompatibility of human ephitelial (HEp-2) cells cultured
      on new injectable iron-modified calcium phosphate cements (IM-CPCs) has been
      investigated in terms of cell adhesion, cell proliferation, and morphology.
      Quantitative MTT-assay and scanning electron microscopy (SEM) showed that cell
      adhesion and viability were not affected with culturing time by iron
      concentration in a dose-dependent manner. SEM-cell morphology showed that HEp-2
      cells, seeded on IM-CPCs, were able to adhere, spread, and attain normal
      morphology. These results showed that the new injectable IM-CPCs have
      cytocompatible features of interest to the intended kyphophasty application, for
      the treatment of osteoporotic vertebral compression fractures.

PMID- 18626752
TI  - Species difference in intestinal absorption mechanism of etoposide and digoxin
      between cynomolgus monkey and rat.
AB  - PURPOSE: The oral bioavailability of some therapeutic agents is markedly lower in
      cynomolgus monkeys than in humans. We investigated small-intestinal absorption of
      the P-glycoprotein (P-gp) substrates etoposide and digoxin in monkeys to clarify
      the influence of efflux transport on their intestinal permeability. METHODS: The
      pharmacokinetics of etoposide and digoxin was examined in monkeys and rats after
      oral and intravenous administration. Intestinal permeability and segmental
      differences in permeability were investigated with an Ussing-type chamber.
      RESULTS: The bioavailability of etoposide was 12.9 and 13.9% in monkeys and rats,
      respectively. Total body clearance of etoposide in monkeys was much less than
      hepatic blood flow, suggesting that the bioavailability would be limited at
      intestinal absorption. Marked vectorial transport of etoposide in the secretory
      direction was observed in rats, especially in the lower small intestine, and
      segmental differences were consistent with the distribution of P-gp expression.
      Vectorial transport was minimal in monkey small intestine. Our kinetic analysis
      indicated that P-gp contributes little to the intestinal permeability of
      etoposide and digoxin in monkeys, and apical uptake is rate-limiting. CONCLUSION:
      Low bioavailability of etoposide in monkeys is due to poor intestinal uptake
      resulting from low influx from the apical side, rather than secretion via P-gp.

PMID- 18626751
TI  - Cancer is a preventable disease that requires major lifestyle changes.
AB  - This year, more than 1 million Americans and more than 10 million people
      worldwide are expected to be diagnosed with cancer, a disease commonly believed
      to be preventable. Only 5-10% of all cancer cases can be attributed to genetic
      defects, whereas the remaining 90-95% have their roots in the environment and
      lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods,
      red meat), alcohol, sun exposure, environmental pollutants, infections, stress,
      obesity, and physical inactivity. The evidence indicates that of all cancer
      related deaths, almost 25-30% are due to tobacco, as many as 30-35% are linked to
      diet, about 15-20% are due to infections, and the remaining percentage are due to
      other factors like radiation, stress, physical activity, environmental pollutants
      etc. Therefore, cancer prevention requires smoking cessation, increased ingestion
      of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise,
      avoidance of direct exposure to sunlight, minimal meat consumption, use of whole
      grains, use of vaccinations, and regular check-ups. In this review, we present
      evidence that inflammation is the link between the agents/factors that cause
      cancer and the agents that prevent it. In addition, we provide evidence that
      cancer is a preventable disease that requires major lifestyle changes.

PMID- 18626754
TI  - Exercise capacity in non-specific chronic low back pain patients: a lean body
      mass-based Astrand bicycle test; reliability, validity and feasibility.
AB  - OBJECTIVE: Measurement of exercise capacity is essential in patients with non
      specific chronic low back pain (CLBP). However, the conventional Astrand bicycle
      test is not feasible in patients with a very poor aerobic capacity. Therefore the
      Astrand bicycles test for non-specific CLBP patients based on lean body mass
      (LBM) was developed as an alternative. The aim of this study was to evaluate
      reliability and validity of the LBM-based Astrand test. SUBJECTS: Twenty patients
      with non-specific CLBP and 20 healthy subjects were included for the reliability
      evaluation, and 19 healthy subjects for the validity evaluation. METHOD: Patients
      and healthy subjects were assessed twice. Intra class correlation (ICC),
      repeatability coefficient (RC) and the limits of agreement (LOA) were calculated
      as a measure of test re-tests reliability. An ICC >or= 0.75 was considered
      acceptable. Validity was tested by calculating ICC between the LBM-based Astrand
      test and a maximal bicycle test. RESULTS: The LBM-based Astrand test shows good
      reliability, reflected by an ICC >or= 0.91 and 95% of the 20 patients could
      perform the test. However, differences with the estimated true value reflected by
      the RC and natural variation reflected by the LOA were substantial in patients.
      Validity was good, reflected by ICC >or= 0.88. CONCLUSION: The present study
      shows that the LBM-based Astrand test is a reliable, valid, and feasible method
      for patients with non-specific CLBP. However, a substantial amount of variation
      should be taken into account in patients when interpreting the test results
      clinically.

PMID- 18626755
TI  - PARAFAC analysis of the quenching of EEM of fluorescence of glutathione capped
      CdTe quantum dots by Pb(II).
AB  - Glutathione capped CdTe quantum dots (QD) were synthesised using a simple
      experimental procedure and two samples were subjected of study (QD550 and QD600).
      The maximum of the excitation and emission spectra and the emission full width of
      half maximum of these two QD were: QD550, 307, 550 and 37 nm; QD600, 307, 600 and
      39 nm. The steady state fluorescence properties of the two QD undergo variation
      when the pH of the aqueous solution is varied and are characterised by different
      apparent pKa: QD550, 5.2+/-0.1; QD600, 6.3+/-0.3. The fluorescence intensity of
      the QD550 is markedly quenched by the presence of micromolar quantities of Pb(II)
      ion (Stern-Volmer constant of about 7x10(5) M(-1)). PARAFAC analysis of the
      excitation emission matrices (EEM) of QD550 acquired as function of the Pb(II)
      ion showed that only one linearly independent component describes the quenching
      of the QD550 by the Pb(II) ion allowing robust estimation of the excitation and
      emission spectra and of the quenching profiles.

PMID- 18626753
TI  - Protective effects of diallyl sulfide, a garlic constituent, on the warm hepatic
      ischemia-reperfusion injury in a rat model.
AB  - PURPOSE: The aim of this study is to evaluate the effects of diallyl sulfide
      (DAS) on the warm hepatic ischemia-reperfusion (IR) injury in a rat model.
      METHODS: Rats (n = 8-10/group) were subjected to sham operation or warm ischemia
      (1 h)-reperfusion (3 h) preceded by a single intraperitoneal dose (1.75 mmol/kg)
      of DAS or vehicle, and relevant biochemical parameters were monitored. RESULTS:
      Warm IR injury caused a significant increase in the plasma markers of liver
      injury, which was attenuated by DAS. The hepatoprotective effects of DAS were
      associated with significant reductions in lipid peroxidation markers and in situ
      generation of superoxide in the liver and increases in the glutathione levels of
      the liver and bile, suggestive of an antioxidant effect for DAS. Additionally,
      DAS caused an almost twofold increase in the protein expression of the liver heme
      oxygenase-1, an enzyme that confers cytoprotection against oxidative stress.
      Whereas the total cytochrome P450 remained unchanged, the protein levels and
      activity of CYP2E1, which plays an important role in the generation of reactive
      oxygen species, significantly decreased by DAS pretreatment. CONCLUSIONS: DAS
      protects the liver from warm IR injury by reducing oxidative stress through, at
      least in part, induction of heme oxygenase-1 and inhibition of CYP2E1.

PMID- 18626756
TI  - The fluorescence enhancement of the protein adsorbed on the surface of Ag
      nanoparticle.
AB  - The fluorescence enhancement of the BSA adsorbed on the surface of Ag
      nanoparticles is reported, where non-fluorescent collagen is used as the
      separator between the BSA and Ag nanoparticles. The study indicates that Ag
      nanoparticles can enhance the fluorescence of the BSA, especially the
      fluorescence of the tyrosine residues with lower quantum. Three types of Ag
      nanoparticles are evaluated including Ag island film, Ag colloids and fractal Ag
      electrode. Of them Ag island film is the best. The investigation suggests that
      the fluorescence enhancement of the BSA is related to the adsorption of the BSA
      on the surface of Ag island film through the hydrophobic interaction, while the
      collagen can promote the adsorption of the BSA on the surface of Ag island film
      and change its conformation, resulting in the interaction between BSA and Ag
      island film.

PMID- 18626757
TI  - A study of the predictors of persistence in stalking situations.
AB  - Stalkers engaging in persistent campaigns of harassment have the potential to
      cause immense harm to their victims and themselves. Being able to estimate which
      stalkers are likely to persist longest is important to clinicians dealing with
      both perpetrators and victims. This study of 200 stalkers investigated
      characteristics of the stalkers and their behaviour that were associated with
      increased persistence. Logistic regression models were developed to predict low,
      moderate, and highly persistent stalking. The results supported previous research
      indicating that the type of prior relationship between stalker and victim is
      strongly associated with persistence, with prior acquaintances the most
      persistent, and strangers least. Being aged over 30, sending the victim
      unsolicited materials, and having an intimacy seeking or resentful motivation was
      also associated with greater persistence, as was the presence of psychosis.

PMID- 18626758
TI  - Ablation of permanent AF: adjunctive strategies to pulmonary veins isolation:
      targeting AF NEST in sinus rhythm and CFAE in AF.
AB  - Atrial fibrillation (AF) is highly prevalent and accounts for significant
      morbidity, mortality, and health care costs. Catheter ablation has become a
      therapeutic option in the management of this challenging arrhythmia. To optimize
      procedure safety and long-term efficacy, innovative technologies and ablation
      strategies have been targeting either the triggers initiating AF or the substrate
      responsible for its maintenance. Pulmonary vein (PV) isolation, initially limited
      to the PVs, has been modified to encompass the left atrial myocardium surrounding
      the PV ostia, namely the LA-PV antra. Our current intracardiac echo-guided
      approach to PV antra isolation, including the adjunct of superior vena cava
      isolation, has likely accounted for higher success rates by electrically
      isolating further AF trigger sites, modifying the substrate for AF maintenance
      and possibly by modulating a dysfunctional autonomic cardiac nervous system.
      However, the long-term outcome following ablation of permanent AF can be further
      improved by incorporating adjunctive ablation strategies to PV isolation, such as
      targeting ablation at sites exhibiting complex atrial fractionated electrograms
      (CFAEs)during AF or at sites exhibiting the so-called AF nests during real-time
      spectral mapping in sinus rhythm.

PMID- 18626759
TI  - Understanding aging in a Middle Eastern context: the SHARE-Israel survey of
      persons aged 50 and older.
AB  - This article describes the development of SHARE-Israel, the survey of persons
      aged 50 and older in Israel, and preliminary results from an early data release.
      The introduction of an HRS-inspired computer-based survey into a Middle East
      country required linguistic and cultural adaptations of the survey mechanisms
      that had not been previously experienced in other countries. Preliminary findings
      showed that the majority group of veteran Jewish-Israelis aged 50 and over is in
      a favorable position in terms of health, employment status and household income
      compared to Arab-Israelis and to new immigrants to Israel from the Former Soviet
      Union. Arab-Israelis aged 50 and over are at greater risk due to greater
      disability and lower incomes. Recent immigrants from the former Soviet Union are
      at greatest risk. They report having the highest degree of depression, long term
      problems and activity limitation, the fewest children, low rates of home
      ownership and low incomes. Comparing the older Israeli population with their
      European counterparts revealed that Israelis are more depressed; more Israeli
      women are employed, and fewer Israeli men are retired; and household income in
      Israel is lower, but rises relatively when correcting for purchasing power
      parity. These trends point to several areas that will require attention in the
      formulation of public policy on behalf of the aging population in Israel.

PMID- 18626760
TI  - Brief report: pragmatic language in autism spectrum disorder: relationships to
      measures of ability and disability.
AB  - Pragmatic language skill is regarded as an area of universal deficit in Autism
      Spectrum Disorder (ASD), but little is known about factors related to its
      development and how it in turn might contribute to skills needed to function in
      everyday contexts or to the expression of ASD-related symptoms. This study
      investigated these relationships in 37 high-functioning children with ASD.
      Multiple regression analyses revealed that structural language skills
      significantly predicted pragmatic language performance, but also that a
      significant portion of variance in pragmatic scores could not be accounted for by
      structural language or nonverbal cognition. Pragmatic language scores, in turn,
      accounted for significant variance in ADOS Communication and Socialization
      performance, but did not uniquely predict level of communicative or social
      adaptive functioning on the Vineland. These findings support the notion of
      pragmatic language impairment as integral to ASD but also highlight the need to
      measure pragmatic skills in everyday situations, to target adaptive skills in
      intervention and to intervene in functional, community-based contexts.

PMID- 18626761
TI  - Engagement with electronic screen media among students with autism spectrum
      disorders.
AB  - This study investigated the relative engagement potential of four types of
      electronic screen media (ESM): animated video, video of self, video of a familiar
      person engaged with an immersive virtual reality (VR) game, and immersion of self
      in the VR game. Forty-two students with autism, varying in age and expressive
      communication ability, were randomly assigned to the experimental conditions.
      Gaze duration and vocalization served as dependent measures of engagement. The
      results reveal differential responding across ESM, with some variation related to
      the engagement metric employed. Preferences for seeing themselves on the screen,
      as well as for viewing the VR scenarios, emerged from the data. While the study
      did not yield definitive data about the relative engagement potential of ESM
      alternatives, it does provide a foundation for future research, including
      guidance related to participant profiles, stimulus characteristics, and data
      coding challenges.

PMID- 18626762
TI  - Multiplex PCR and quality control of Epinotia aporema granulovirus production.
AB  - A specific multiplex PCR was developed for the rapid and highly sensitive quality
      control of the viral DNA during Epinotia aporema granulovirus (EpapGV)
      production. At the beginning of this work only 2.3% of the EpapGV genomic
      sequence was known. In order to increase the availability of specific
      information, the terminal sequences of the inserts of several selected clones of
      EpapGV genomic libraries were determined. These data comprised 8.4% of the total
      DNA sequence and corresponded to regions distributed throughout the genome. Based
      on the small fraction of known sequence available a set of 32 primers was
      designed, using information theory to set the basis for this study. Each pair of
      designed primers was initially tested in individual PCRs to assess the correct
      size of the expected product and the sensitivity of the amplification. The
      specificity was verified in multiplex PCRs, using alternatively 1-3 sets of
      selected 5-6 primer pairs and EpapGV DNA preparations from different sources and
      degrees of purity. The results indicate that the multiplex PCR could be used for
      quality control in the bioinsecticide production, as well as in other
      applications such as the detection of latent infections in E. aporema colonies,
      and studies related to virus distribution, vertical transmission, host range, or
      persistence in the field.

PMID- 18626763
TI  - Characterization of Citrus tristeza virus strains from southern China based on
      analysis of restriction patterns and sequences of their coat protein genes.
AB  - Citrus tristeza virus (CTV) isolates collected from southern China were
      characterized by biological indexing on citrus indicators, restriction fragment
      length polymorphism (RFLP), and bi-directional reverse transcription-polymerase
      chain reaction (BD-PCR) analysis of their coat protein (CP) genes. Of the 30
      isolates, only two isolates, N3 and N4, did not induce visible symptoms. Twenty
      eight other isolates induced stem pitting and vein clearing, plant stunting, and
      leaf yellowing symptoms on Mexican lime, Duncan grapefruit, and sour orange
      seedlings. In BD-PCR analysis, a 392-bp fragment specific for the mild strains
      was amplified from isolates N3 and N4, and a 320-bp fragment specific for the
      severe strains was produced from the other 28 isolates. The RFLP analysis for RT
      PCR products of the CP gene with restriction enzyme HinfI identified seven groups
      representing groups I-VI and a new group, which was not involved in the seven
      groups defined by Gillings (J Virol Methods 44:305-317, 1993). The sequences of
      the CP genes from 12 Chinese CTV isolates showed a high divergence, with 91.5
      99.7% identities at the nucleotide level and 94.2-99.6% identities at the amino
      acid level. Our results suggest that the composition of CTV populations from
      China has a high genetic diversity in the CP gene.

PMID- 18626767
TI  - External and internal factors influencing happiness in elite collegiate athletes.
AB  - When under conditions of high demand and allostatic load, are happiness and
      satisfaction in four domains (family, friends, academics, recreation) influenced
      more by external or internal factors? Do student-athletes who lead exceedingly
      complicated lives report happiness as a function of athletic achievement or
      internal disposition? Stanford student-athletes (N=140) were studied with a
      standardized questionnaire which examined internal factors ((1) locus of control,
      (2) mindfulness, (3) self-restraint, and (4) self-esteem) to see whether they
      better account for happiness than external factors (playing time, scholarship).
      As predicted, internal factors were more powerful correlates of happiness when
      holding constant demographics. Regression models differed for different aspects
      of happiness, but the main postulated result of internal versus external was
      maintained throughout. These findings have implications for how well athletes
      cope with adversity which, in turn, could shed light on the development of traits
      that may provide a buffer against adversity and build resilience.

PMID- 18626766
TI  - A randomized trial of a mental health consumer-managed alternative to civil
      commitment for acute psychiatric crisis.
AB  - This experiment compared the effectiveness of an unlocked, mental health consumer
      managed, crisis residential program (CRP) to a locked, inpatient psychiatric
      facility (LIPF) for adults civilly committed for severe psychiatric problems.
      Following screening and informed consent, participants (n = 393) were randomized
      to the CRP or the LIPF and interviewed at baseline and at 30-day, 6-month, and 1
      year post admission. Outcomes were costs, level of functioning, psychiatric
      symptoms, self-esteem, enrichment, and service satisfaction. Treatment outcomes
      were compared using hierarchical linear models. Participants in the CRP
      experienced significantly greater improvement on interviewer-rated and self
      reported psychopathology than did participants in the LIPF condition; service
      satisfaction was dramatically higher in the CRP condition. CRP-style facilities
      are a viable alternative to psychiatric hospitalization for many individuals
      facing civil commitment.

PMID- 18626764
TI  - Randomized controlled trial of a cognitive-behavioral intervention for HIV
      positive persons: an investigation of treatment effects on psychosocial
      adjustment.
AB  - Questions remain regarding the clinical utility of psychological interventions
      for HIV-positive persons because randomized controlled trials have utilized
      stringent inclusion criteria and focused extensively on gay men. The present
      randomized controlled trial examined the efficacy of a 15-session, individually
      delivered cognitive-behavioral intervention (n = 467) compared to a wait-list
      control (n = 469) in a diverse sample of HIV-positive persons who reported HIV
      transmission risk behavior. Five intervention sessions that dealt with executing
      effective coping responses were delivered between baseline and the 5 months post
      randomization. Additional assessments were completed through 25 months post
      randomization. Despite previously documented reductions in HIV transmission risk,
      no intervention-related changes in psychosocial adjustment were observed across
      the 25-month investigation period. In addition, there were no intervention
      effects on psychosocial adjustment among individuals who presented with mild to
      moderate depressive symptoms. More intensive mental health interventions may be
      necessary to improve psychosocial adjustment among HIV-positive individuals.

PMID- 18626769
TI  - Management of radial sclerosing lesions of the breast diagnosed using
      percutaneous vacuum-assisted core needle biopsy: recommendations for excision
      based on seven years' of experience at a single institution.
AB  - BACKGROUND: Radial sclerosing lesions (RSLs) of the breast are benign lesions
      that can mimic carcinoma on mammography and are frequently associated with
      malignancy. Guidelines for the selection of patients with RSL on core needle
      biopsy who require surgical excision are not well defined. We describe the
      clinical management of RSL diagnosed using a percutaneous vacuum-assisted 9- or
      11-gauge stereotactically guided core needle biopsy (SCNB) device. METHODS: We
      retrospectively evaluated data on patients with mammographically detected RSLs
      sampled by SCNB between 2001 and 2007. Demographic data, the size and type of
      lesion and histological findings were correlated with subsequent surgical
      excision data. Clinical and radiological follow-up data were collected. RESULTS:
      Among 80 patients with RSLs, 19 underwent surgical excision, and 61 had
      mammographic surveillance only. RSLs associated on imaging with an underlying
      architectural distortion were more frequently excised than those associated with
      calcifications (P = 0.003). The presence of residual calcifications/architectural
      distortion on post-biopsy mammogram significantly correlated with subsequent
      excision (P = 0.00003). Proliferative and/or atypical RSLs were more often
      excised than nonproliferative RSLs (P = 0.00001). In two patients, proliferative
      RSL was upgraded to atypical RSL on excision. Clinical and mammographic follow-up
      for a mean of 32 months (standard deviation, +/- 23) in the group without
      excision showed no cancer. CONCLUSIONS: Architectural distortion on imaging,
      residual abnormality on post-biopsy mammogram and the presence of proliferative
      changes and/or epithelial atypia on SCNB were parameters leading to increased
      performance of surgical excision in our series. No diagnoses were upgraded to
      malignancy after excision of RSLs, suggesting that more extensive sampling by a 9
      or 11-gauge SCNB device, followed by meticulous correlation of radiological and
      pathological findings and close clinical/radiological follow-up, could obviate
      surgical excision in the majority of RSL cases without associated atypia on SCNB.

PMID- 18626768
TI  - The effect of parenting stress on child behavior problems in high-risk children
      with prenatal drug exposure.
AB  - OBJECTIVE: To examine the relationship between early parenting stress and later
      child behavior in a high-risk sample and measure the effect of drug exposure on
      the relationship between parenting stress and child behavior. METHODS: A subset
      of child-caregiver dyads (n=607) were selected from the Maternal Lifestyle Study
      (MLS), which is a large sample of children (n=1,388) with prenatal cocaine
      exposure and a comparison sample unexposed to cocaine. Of the 607 dyads, 221 were
      prenatally exposed to cocaine and 386 were unexposed to cocaine. Selection was
      based on the presence of a stable caregiver at 4 and 36 months with no evidence
      of change in caregiver between those time points. RESULTS: Parenting stress at 4
      months significantly predicted child externalizing behavior at 36 months. These
      relations were unaffected by cocaine exposure suggesting the relationship between
      parenting stress and behavioral outcome exists for high-risk children regardless
      of drug exposure history. CONCLUSIONS: These results extend the findings of the
      relationship between parenting stress and child behavior to a sample of high-risk
      children with prenatal drug exposure. Implications for outcome and treatment are
      discussed.

PMID- 18626770
TI  - Methodological structure for aggression research.
AB  - Kendler's seminal essay listed 8 major propositions outlining a philosophical
      framework for the entire field of psychiatry [Kendler (American Journal of
      Psychiatry 162:433-440, 2005)]. These propositions have grounded psychiatric
      research on a coherent conceptual basis. The field of aggression research needs a
      general conceptual framework that would help us to integrate the contributions of
      neurobiology, sociology, criminology, and other areas. All of Kendler's
      propositions are generally relevant in this respect. The aim of the current
      article is to develop specific applications of four of Kendler's propositions for
      aggression research. These four propositions are: "Psychiatry is irrevocably
      grounded in mental, first-person experiences", "Psychiatric disorders are
      etiologically complex, and we can expect no more "spirochete-like" discoveries
      that will explain their origin in simple terms", "Explanatory pluralism is
      preferable to monistic explanatory approaches, especially biological
      reductionism", and "Acceptance of Patchy Reductionism".

PMID- 18626771
TI  - Design optimization for bioMEMS studies of enzyme-controlled metabolic pathways.
AB  - Biological microelectromechanical systems (bioMEMS) provide an attractive
      approach to understanding and modifying enzymatic pathways by separating and
      interrogating individual reaction steps at localized sites in a microfluidic
      network. We have previously shown that electrodeposited chitosan enables
      immobilization of an enzyme at a specific site while maintaining its catalytic
      activity. While promising as a methodology to replicate metabolic pathways and
      search for inhibitors as drug candidates, these investigations also revealed
      unintended (or parasitic) effects, including products generated by the enzyme
      either (1) in the homogeneous phase (in the liquid), or (2) nonspecifically bound
      to microchannel surfaces. Here we report on bioMEMS designs which significantly
      suppress these parasitic effects. To reduce homogeneous reactions we have
      developed a new packaging and assembly strategy which eliminates fluid reservoirs
      that are commonly used for fluidic interconnects with external tubing. To
      suppress reactions by nonspecifically bound enzyme on microchannel walls we have
      implemented a cross-flow microfluidic network design so that enzyme flow for
      assembly and substrate/product for reaction share only the region where the
      enzyme is immobilized at the intended reaction site. Our results show that the
      signal-to-background ratio of sequential enzymatic reactions increases from 0.72
      to 1.28 by eliminating the packaging reservoirs, and increases to 2.43 by
      separating the flow direction of enzymatic reaction from that of enzyme assembly
      step. These techniques can be easily applied to versatile microfluidic devices to
      minimize parasitic reactions in sequential biochemical reactions.

PMID- 18626772
TI  - A novel anti-HIV dextrin-zidovudine conjugate improving the pharmacokinetics of
      zidovudine in rats.
AB  - The aim of this study was to investigate a newly synthesized dextrin-zidovudine
      (AZT) conjugate designed as a sustained release prodrug of AZT for parenteral
      administration. AZT was first reacted with succinic anhydride to form a
      succinoylated AZT which was subsequently coupled with dextrin to yield the
      dextrin-AZT conjugate. The structure of the conjugate was characterized by FT-IR
      and (1)H-NMR spectroscopy. The drug content of the conjugate was 18.9 wt.%. The
      release in vitro of free AZT and succinoylated AZT was investigated in buffer
      solutions at pH 5.5 and 7.4 and in human plasma. AZT and succinoylated AZT
      release from the conjugate was 1.4% (pH 5.5), 41.7% (pH 7.4) and 78.4% in human
      plasma after 24 h. Release was complete in human plasma after 48 h. A
      pharmacokinetic study in rats following intravenous administration of the
      conjugate showed prolonged plasma levels of AZT compared to free AZT. The use of
      the conjugate extended the plasma half-life of AZT from 1.3 to 19.3 h and the
      mean residence time from 0.4 to 23.6 h. Furthermore, the conjugate provided a
      significant greater area under the plasma concentration-time curve and reduced
      the systemic clearance of AZT. This study suggested the potential of this novel
      dextrin-AZT conjugate as a new intravenous preparation of AZT.

PMID- 18626773
TI  - Design and evaluation of a sustained release gastroretentive dosage form of
      captopril: a technical note.

PMID- 18626774
TI  - Antibacterial activity and drug release of chitosan sponge containing doxycycline
      hyclate.
AB  - The purpose of the present study was to develop and characterize the chitosan
      sponges loading with doxycycline hyclate and their antibacterial activities. The
      pore density of chitosan sponge prepared with freeze drying technique was
      increased as the higher concentrated chitosan solution was used. The sponge
      prepared from 10% w/w of the chitosan solution and crosslinking with
      glutaraldehyde solution was utilized for loading with doxycycline hyclate. The
      drug release and sustainable antibacterial activity of fabricated sponge were
      assessed using dissolution test and agar diffusion test, respectively. Drug
      release from non-crosslinked sponge into phosphate buffer pH7.4 was slower than
      that from crosslinked sponge since the former could absorb the medium and form
      gel to retard the initial drug diffusion. Sustainable antibacterial activity of
      developed sponge was evident against S. aureus and E. coli. In conclusion, the in
      vitro release profile and antibacterial efficiency indicated that doxycycline
      hyclate could be sustained using chitosan sponge.

PMID- 18626775
TI  - High-resolution pyrimidine- and ribose-specific 4D HCCH-COSY spectra of RNA using
      the filter diagonalization method.
AB  - The NMR spectra of nucleic acids suffer from severe peak overlap, which
      complicates resonance assignments. 4D NMR experiments can overcome much of the
      degeneracy in 2D and 3D spectra; however, the linear increase in acquisition time
      with each new dimension makes it impractical to acquire high-resolution 4D
      spectra using standard Fourier transform (FT) techniques. The filter
      diagonalization method (FDM) is a numerically efficient algorithm that fits the
      entire multi-dimensional time-domain data to a set of multi-dimensional
      oscillators. Selective 4D constant-time HCCH-COSY experiments that correlate the
      H5-C5-C6-H6 base spin systems of pyrimidines or the H1'-C1'-C2'-H2' spin systems
      of ribose sugars were acquired on the (13)C-labeled iron responsive element (IRE)
      RNA. FDM-processing of these 4D experiments recorded with only 8 complex points
      in the indirect dimensions showed superior spectral resolution than FT-processed
      spectra. Practical aspects of obtaining optimal FDM-processed spectra are
      discussed. The results here demonstrate that FDM-processing can be used to obtain
      high-resolution 4D spectra on a medium sized RNA in a fraction of the acquisition
      time normally required for high-resolution, high-dimensional spectra.

PMID- 18626776
TI  - Heeding community voices in medical futility guidelines.

PMID- 18626777
TI  - Expression and colocalization of NADPH-diaphorase and heme oxygenase-2 in
      trigeminal ganglion and mesencephalic trigeminal nucleus of the rat.
AB  - Carbon monoxide (CO) and nitric oxide (NO) are two endogenously produced gases
      that can function as second messenger molecules in the nervous system. The enzyme
      systems responsible for CO and NO biosynthesis are heme oxygenase (HO) and nitric
      oxide synthase (NOS), respectively. The present study was undertaken to examine
      the distribution of HO-2 and NOS of the trigeminal primary afferent neurons of
      the rat, located in the trigeminal ganglion (TG) and mesencephalic trigeminal
      nucleus (MTN), using histochemistry and immunohistochemistry. NADPH-d staining
      was found in most neurons in TG. The intensely NADPH-d-stained neurons were small
      or medium-sized, while the large-sized neurons were less intensely stained.
      Immunocytochemistry for HO-2 revealed that almost all neurons in TG expressed HO
      2, but they did not appear cell size-specific pattern. NADPH-d and HO-2 positive
      neurons appeared the same pattern, which was NADPH-d activity and HO-2 expression
      progressively declined from the caudal to rostral part of the MTN. A double
      staining revealed that the colocalization of NADPH-d/HO-2 neurons was 97.3% in TG
      and 97.6% in MTN. The remarkable parallels between NADPH-d and HO-2 suggest that
      NO and CO are likely neurotransmitters and mediate the orofacial nociception and
      sensory feedback of the masticatory reflex arc together.

PMID- 18626778
TI  - Mercury and other metals in eggs and feathers of glaucous-winged gulls (Larus
      glaucescens) in the Aleutians.
AB  - Levels of mercury and other contaminants should be lower in birds nesting on
      isolated oceanic islands and at high latitudes without any local or regional
      sources of contamination, compared to more urban and industrialized temperate
      regions. We examined concentrations of arsenic, cadmium, chromium, lead,
      manganese, mercury and selenium in the eggs, and the feathers of fledgling and
      adult glaucous-winged gulls (Larus glaucescens) nesting in breeding colonies on
      Adak, Amchitka, and Kiska Islands in the Aleutian Chain of Alaska in the Bering
      Sea/North Pacific. We tested the following null hypotheses: 1) There were no
      differences in metal levels among eggs and feathers of adult and fledgling
      glaucous-winged gulls, 2) There were no differences in metal levels among gulls
      nesting near the three underground nuclear test sites (Long Shot 1965, Milrow
      1969, Cannikin 1971) on Amchitka, 3) There were no differences in metal levels
      among the three islands, and 4) There were no gender-related differences in metal
      levels. All four null hypotheses were rejected at the 0.05 level, although there
      were few differences among the three test sites on Amchitka. Eggs had the lowest
      levels of cadmium, lead, and mercury, and the feathers of adults had the lowest
      levels of selenium. Comparing only adults and fledglings, adults had higher
      levels of cadmium, chromium, lead and mercury, and fledglings had higher levels
      of arsenic, manganese and selenium. There were few consistent interisland
      differences, although levels were generally lower for eggs and feathers from
      gulls on Amchitka compared to the other islands. Arsenic was higher in both adult
      feathers and eggs from Amchitka compared to Adak, and chromium and lead were
      higher in adult feathers and eggs from Adak compared to Amchitka. Mercury and
      arsenic, and chromium and manganese levels were significantly correlated in the
      feathers of both adult and fledgling gulls. The feathers of males had
      significantly higher levels of chromium and manganese than did females. The
      levels of most metals in feathers are below those known to be associated with
      adverse effects in the gulls or their predators. However, levels of mercury in
      some gull eggs are within a range suggesting that several eggs should not be
      eaten in one day by sensitive humans.

PMID- 18626779
TI  - Synthesis and structure characterization of new 1,2,4-oxadiazolo[4,5-d]-1,5
      benzothiazepines derivatives containing 2-phenyl-1,2,3-triazole through 1,3
      dipolar cycloaddition reaction.
AB  - Reaction of 1,5-benzothiazepines, containing 2-phenyl-1,2,3-triazole 2a-d, with
      aryl nitrile oxides in CH2 Cl2 at room temperature leads to a series of novel
      1,2,4-oxadiazolo[4,5-d]-1,5-benzothiazepine derivatives 3a-l in good yields. The
      products were characterized by IR, 1H NMR, MS, elemental analyses, X-ray and
      their spectrum characters were discussed.

PMID- 18626780
TI  - Choice of breeding stock, preference of production traits and culling criteria of
      village chickens among Zimbabwe agro-ecological zones.
AB  - Free ranging chickens reared by smallholder farmers represent genetic diversity
      suited for particular environments and shaped by the socio-economic and cultural
      values of the farming systems. This study sought to investigate the existence of
      chicken strains and evaluate the breeding goals and strategies used by village
      chicken farmers in Zimbabwe. A semi-structured questionnaire was administered to
      97, 56, 70, 104 and 37 households randomly selected from five agro-ecological
      zones I-V, respectively. Fifteen chicken strains mostly defined by morphological
      traits were reported in the five eco-zones. Production criteria such as body
      size, and fertility were highly ranked (ranging from 1.3-2.6) by farmers across
      all the eco-zones, while cultural traits were the least preferred production
      traits. As a common breeding practice, farmers chose the type of hens and cocks
      to retain for breeding purposes and these randomly mixed and mated with others
      from community flocks. Chicken body size was ranked the major determinant in
      choosing breeding animals followed by mothering ability, and fertility. More
      households culled chickens associated with poor reproductive performance, poor
      growth rates and those intolerant to disease pathogens. The focus on many
      negatively correlated production traits and the absence of farmer records
      compromises breeding strategies in these production systems.

PMID- 18626781
TI  - Some observations on sheep sarcoptic mange in Tehran province, Iran.
AB  - Sarcoptes scabiei infestation was diagnosed in 278 sheep from 12 fatling flocks.
      The sheep presented crusted skin lesions initially appear on the lips or
      nostrils, the lesion on nostrils also extend towards around the eyes, the
      supraorbital fossae and in some cases over entire face. The infested male lambs
      by mating behavior in fatling flocks caused transmitting the infection to fat
      tail area and scrotum. Histopathological study of lesions demonstrated marked
      acanthosis, hyperkeratosis, parakeratosis. Tunnels could be observed in the
      hyperkeratotic stratum corneum and mite segments were located mainly in the
      stratum corneum and also in the stratum granulosum. Attempts to eliminate S.
      scabiei var. ovis were made in 3 naturally infested sheep herds, by two dippings
      with two weeks interval with Amitraz, Cypermetrin and Prompetamphos. The results
      of this study indicate that acaricidal treatment of S. scabiei var. ovis in 3
      naturally infested herds was successful, but a few cases of reinfestation were
      found in each treated group.

PMID- 18626782
TI  - Growth characteristic of Camel pox and Vaccinia viruses in embryonated eggs and
      cell culture.
AB  - Camel pox viruses isolated in Sudan and VD45 (African camel pox strain) and
      Vaccinia virus (Elstree strain) were used for inoculation of chorioallantoic
      membrane (CAM) of embryonated eggs (EE) and cell culture (CC). In EE Lesions were
      seen as pocks ranging in size from 1 to 1.5 mm in diameter, and they increase in
      size with serial passage and taking opaque- white and opaque- yellow colors. When
      propagated in Vero cells, these viruses gave clear CPE, characterized by rounding
      of cells, plaque formation, syncytia and detachment of cells from the glass.

PMID- 18626783
TI  - An assessment of the clinical utility of transperineal urethrosphincteric block
      (TUSB) in outpatient rigid cystoscopy: a single-blind, randomized study.
AB  - BACKGROUND AND OBJECTIVES: Pain control in outpatient rigid cystoscopy is often
      achieved via the application of intraurethral lidocaine jelly. This clinical
      trial was designed to test the effectiveness and safety of a new method to
      provide local anesthesia, transperineal urethrosphincteric block (TUSB), prior to
      rigid cystoscopy. METHODS: Male patients posted for outpatient rigid cystoscopy
      were randomized to receive TUSB (group A) using 10-20 ml of 1% lidocaine,
      intraurethral 30 ml of 2% lidocaine jelly (group B) or intraurethral 30 ml of
      neutral jelly (group C) as a method of pain control. Following the procedure,
      plasma concentrations of lidocaine were measured in group A patients. Outcome
      assessments included mean urethral and sphincteric numerated pain scores (0-10),
      overall discomfort level (0-4) and plasma lidocaine levels. RESULTS: One hundred
      and fifty patients were recruited, 50 in each group. When the three groups were
      compared, the ratio of group A patients with sphincteric pain score >or=2 was
      significantly the least. Also, the ratio of group A patients with discomfort
      level >or=2 was significantly less than the same ratio in either group B or C.
      Plasma lidocaine concentrations were within nontoxic levels and never exceeded
      2.83 microg/ml in 39 subjects. CONCLUSION: This study demonstrates that TUSB is
      an effective and safe method in significantly relieving the pain associated with
      outpatient rigid cystoscopy. TUSB may offer urologists and anesthetists an
      alternative way to achieve pain control besides intraurethral lidocaine jelly
      during rigid cystoscopy.

PMID- 18626784
TI  - The protective effect of erythropoietin infusion on testicular torsion/detorsion:
      an experimental study.
AB  - INTRODUCTION: The aim of the present study was to evaluate the effects of
      erythropoietin (EPO) on the histopathology of testes after unilateral testicular
      torsion and detorsion. MATERIALS AND METHODS: Twenty-five male Sprague-Dawley
      rats weighing 120 g were used in this study. The rats were randomly divided into
      three groups, a sham group consisting of five rats and the other two groups
      consisting of ten rats. In group 1 (sham group), right orchiectomy with no
      additional intervention was performed. In group 2 (T/D group), torsion was
      created by rotating the testis 720 degrees in a clockwise direction for 4 h.
      After a 4-h torsion period, the right testis was detorted and replaced into the
      scrotum for 4 h. After the torsion, 0.5 cc 0.9% NaCl solution was injected once
      and three times in a week (total 12 doses). In group 3 (T/D + erythropoietin; EPO
      group), the same surgical procedure was done as in group 1, but EPO 1,000 IU/kg
      was injected just before the detorsion and three times in a week. At the end of
      each procedure, bilateral orchiectomies were performed for the histopathological
      examinations in all groups. RESULTS: We examined the testes weight,
      vascularization of the region between the seminiferous tubules, percentage of
      necrotic seminipherous tubules, and maturation of spermatogenesis in terms of
      necrosis, sertoli cells, maturation arrest of spermatogenesis,
      hypospermatogenesis, and normal spermatogenesis of torsioned testis tissues with
      and without EPO treatment. Extremely significant differences in testicular weight
      were observed in group 1 compared to groups 2 and 3 (P < 0.001). CONCLUSION:
      Administration of EPO significantly influenced the rescue of testicular function
      by preserving the intact seminiferous tubular morphology, lowering the percentage
      of necrotic seminipherous tubules, and significantly reducing histological damage
      (P < 0.05).

PMID- 18626785
TI  - Prostatic profile, premature ejaculation, erectile function and andropause in an
      at-risk Mexican population.
AB  - OBJECTIVE: To determine the frequency of prostatic symptomatology, premature
      ejaculation (PE), erectile function, symptoms in the older adult/andropause
      assessment and to determine the risk factors involved. MATERIALS AND METHODS: The
      study was conducted by the Mexican Society of Urology and was carried out from
      June to October 2006. Epidemiological information was obtained through the
      completion of four validated questionnaires by patients receiving non
      institutional urology treatment. The large database was statistically analyzed
      using a logistic regression model. RESULTS: A total of 1,779 men with an average
      age of 56.6 years were included in the study. The average prostate-specific
      antigen value in the sample was 1.73 (n = 1,316). Prostatic symptomatology in
      accordance with the international prostate symptom score was 7.96 points. A total
      of 41.9% of participants reported experiencing PE. The average time to reach
      ejaculation was 10.97 min. Of the participating individuals, 39.5% were diagnosed
      with andropause. Prostatic symptomatology was associated with risk factors of age
      and prostatitis, P < 0.01. Premature ejaculation and erectile dysfunction were
      associated with age, P < 0.01. Vasomotor problems in the older adult were
      identified with an association tendency towards alcoholism and excess weight, P <
      0.063, but without statistical significance. Sexual problems in the older adult
      were associated with diabetes mellitus, P < 0.01. Andropause was associated with
      traumatic problems in general.

PMID- 18626786
TI  - Directing the evolution of Rubisco and Rubisco activase: first impressions of a
      new tool for photosynthesis research.
AB  - During the last decade the practice of laboratory-directed protein evolution has
      become firmly established as a versatile tool in biochemical research by enabling
      molecular evolution toward desirable phenotypes or detection of novel structure
      function interactions. Applications of this technique in the field of
      photosynthesis research are still in their infancy, but recently first steps have
      been reported in the directed evolution of the CO(2)-fixing enzyme Rubisco and
      its helper protein Rubisco activase. Here we summarize directed protein evolution
      strategies and review the progressive advances that have been made to develop and
      apply suitable selection systems for screening mutant forms of these enzymes that
      improve the fitness of the host organism. The goal of increasing photosynthetic
      efficiency of plants by improving the kinetics of Rubisco has been a long-term
      goal scoring modest successes. We discuss how directed evolution methodologies
      may one day be able to circumvent the problems encountered during this venture.

PMID- 18626787
TI  - Comparison of ECG-gated versus non-gated CT ventricular measurements in thirty
      patients with acute pulmonary embolism.
AB  - OBJECTIVE: To prospectively compare cardiac ventricular measurements from non
      gated CT and end-diastolic ECG-gated CT in patients with acute pulmonary embolism
      (PE). MATERIALS AND METHODS: With institutional review board approval, 30 adult
      patients (16 female, mean age = 56 years, range = 26-77 years) underwent ECG
      gated cardiac CT within 36 h of their CT diagnosis of acute PE to assess the
      right ventricle (RV). The axial and reformatted four-chamber ventricular
      diameters, areas and volumes were measured for both the non-gated CT and the ECG
      gated CT in end-diastole and end-systole. Spearman's rank correlation coefficient
      (RCC) was calculated to compare measurements from the non-gated CT to the gated
      end-diastolic measurements. The median absolute differences between the gated and
      non-gated measurements relative to the gated measurements were provided to
      summarize the degree to which the two measurements differ. A statistical model
      was constructed to test for potential improvement in specificity for the
      prediction of 30-day mortality after acute PE using right ventricular
      measurements from ECG-gated CT versus non-gated CT. RESULTS: The RCC (0.90
      confidence interval) for non-gated and ECG-gated end-diastolic four-chamber and
      axial RV/LV diameter ratios were 0.83 (0.68-0.90) and 0.88 (0.74-0.95). The
      median absolute percent differences suggested a high degree of concordance
      between gated and non-gated measurements. The statistical model predicted that
      measuring the RV/LV diameter ratio from end-diastole using ECG-gated CT rather
      than non-gated CT would yield a potential improvement in specificity for death
      after PE of 0.035 (0.020-0.060) for axial diameter ratios and 0.035 (0.020-0.055)
      for four-chamber diameter ratios. CONCLUSION: The benefit from a separate ECG
      gated CT scan for the evaluation of RV ventricular diameter, area, and volume
      measurements is minimal and does not justify its routine clinical use.

PMID- 18626788
TI  - Longitudinal left ventricular systolic function is impaired in patients with
      coronary slow flow.
AB  - Slow coronary flow (SCF) is a well recognized clinical entity, characterized by
      delayed opacification of coronary arteries in the presence of normal coronary
      angiogram. There is currently no data evaluating myocardial systolic function in
      SCF phenomenon. This study was performed to evaluate regional and global systolic
      function using tissue Doppler imaging (TDI), strain (S) and strain rate imaging
      (SRI) in patients with slow coronary flow. A total of 35 patients with slow
      coronary flow and otherwise normal coronary arteries (mean age 48 +/- 7 years)
      (SCF group) and 21 patients with normal coronary angiograms (mean age 50 +/- 12
      years) (control group) were included in the study. These patients were
      prospectively assessed for evaluation of regional and global left ventricular
      function by conventional echocardiography, systolic TDI, peak S, and peak
      systolic strain rates (SRs) There was a significant difference in peak SRs (-1.1
      +/- 0.2 vs. -1.8 +/- 0.2 1/s, P < or = 0.0001) but similar in systolic TDI (42 +/
      20 vs. 44 +/- 21 mm/s, P = 0.77) and S (20.7 +/- 7.7 vs. 23.7 +/- 8.8, P = 0.14)
      between groups. SRs showed a good correlation with mean TIMI frame count (r = 
      0.80, P < or = 0.0001). As the number of coronary artery with SCF increased
      global strain rate decreased further. In case of one or two or three coronary
      artery with SCF global strain rates were 1.4 +/- 0.2; 1.1 +/- 0.3; 0.9 +/- 0.2
      1/s, respectively, P < or = 0.0001. Although ejection fraction was preserved,
      global and regional strain rate were decreased in SCF. In brief, there is an
      impairment in longitudinal left ventricular systolic function in patients with
      SCF.

PMID- 18626789
TI  - Fresh cortical autograft versus fresh cortical allograft effects on experimental
      bone healing in rabbits: radiological, histopathological and biomechanical
      evaluation.
AB  - Bone grafting is used to enhance healing in osteotomies, arthrodesis, and
      multifragmentary fractures and to replace bony loss resulting from neoplasia or
      cysts. They are source of osteoprogenitor cells and induce bone formation and
      provide mechanical support for vascular and bone ingrowth. Autografts are used
      commonly but quantity of harvested bone is limit. This study was designed to
      evaluate fresh cortical autograft and allograft effects on bone healing process.
      Twenty male White New Zealand rabbits were used in this study. In autograft group
      the defect was filled by fresh autogenous cortical graft, in allograft group the
      defect was filled by a segment of fresh allogenous cortical bone which was
      harvested at the time of surgery during the creation of radius bone defect. Then
      all surface soft tissue, such as muscle attachments, were removed from the
      harvested bone and changed between rabbits as a fresh allogenous cortical bone
      graft and was fixed by cercelage wire. Radiological, histopathological and
      biomechanical evaluations were performed blindly and results scored and analyzed
      statistically. Statistical tests did not support significant differences between
      two groups at the 14th and 56th postoperative day radiographically (P > 0.05).
      There was a significant difference radiologically for the 28th and the 42nd
      postoperative (P < 0.05). Autograft was superior to allograft at the 28th and
      42nd postoperative day in radiological evaluation (P < 0.03). Histopathological
      and biomechanical evaluation revealed no significant differences between two
      groups.

PMID- 18626790
TI  - Imagining the future of photoacoustic mammography.
AB  - How can a realistic ethical imagination about the future of a technology take
      shape? This article contains a reflection which is based on the experiences of an
      embedded ethicist in the context of biophysical research conducive to the
      development of photoacoustic mammography, which is intended for the non-invasive
      detection of breast cancer. Imagination in this context already informs the
      activities of the biophysical researchers, but its role is limited: biophysical
      future scenarios concentrate on the technological advances that photoacoustics
      could bring about. In this article it is argued that it is advisable to also
      consider the medical practice and the ways in which this practice is likely to
      change as an effect of the introduction of photoacoustic mammography into it. On
      the basis of this more encompassing imaginative endeavor it is possible to get a
      clearer idea about how new technologies are able to contribute to human well
      being, which is informative for the setting of research-goals/priorities and a
      responsible implementation of new technologies into the world.

PMID- 18626791
TI  - The microtubule-associated protein, NUD-1, exhibits chaperone activity in vitro.
AB  - Regulation of cell division requires the concerted function of proteins and
      protein complexes that properly mediate cytoskeletal dynamics. NudC is an
      evolutionarily conserved protein of undetermined function that associates with
      microtubules and interacts with several key regulators of mitosis, such as polo
      kinase 1 (Plk1) and dynein. NudC is essential for proper mitotic progression, and
      homologs have been identified in species ranging from fungi to humans. In this
      paper, we report the characterization of the Caenorhabditis elegans NudC homolog,
      NUD-1, as a protein exhibiting molecular chaperone activity. All NudC/NUD-1
      proteins share a conserved p23/HSP20 domain predicted by three-dimensional
      modeling [Garcia-Ranea, Mirey, Camonis, Valencia, FEBS Lett 529(2-3):162-167,
      2002]. We demonstrate that nematode NUD-1 is able to prevent the aggregation of
      two substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric
      concentrations. Further, NUD-1 also protects the native state of CS from thermal
      inactivation by significantly reducing the inactivation rate of this enzyme. To
      further determine if NUD-1/substrate complexes were productive or simply "dead
      end" unfolding intermediates, a luciferase refolding assay was utilized.
      Following thermal denaturation, rabbit reticulocyte lysate and ATP were added and
      luciferase activity measured. In the presence of NUD-1, nearly all of the
      luciferase activity was regained, indicating that unfolded intermediates
      complexed with NUD-1 could be refolded. These studies represent the first
      functional evidence for a member of this mitotically essential protein family as
      having chaperone activity and facilitates elucidation of the role such proteins
      play in chaperone complexes utilized in cell division. C. elegans NUD-1 is a
      member of an evolutionary conserved protein family of unknown function involved
      in the regulation of cytoskeletal dynamics. NUD-1 and its mammalian homolog,
      NudC, function with the dynein motor complex to ensure proper cell division, and
      knockdown or overexpression of these proteins leads to disruption of mitosis. In
      this paper, we show that NUD-1 possesses ATP-independent chaperone activity
      comparable to that of small heat shock proteins and cochaperones and that changes
      in phosphorylation state functionally alter chaperone activity in a
      phosphomimetic NUD-1 mutant.

PMID- 18626792
TI  - Wound healing from a cellular stress response perspective.
AB  - This meeting review highlights areas of mutual interest to investigators in the
      cellular stress response field and to those carrying out wound-healing research.
      Inflammation, perhaps the major unifying theme of this meeting, is an essential
      component of the adult wound response and understanding the control of
      inflammation is a common interest shared with researchers of the cellular stress
      response. The particular interest of the authors of this review is in chronic non
      healing wounds that frequently occur in patients with major illnesses such as
      diabetes and diseases of the blood vessels. This orientation has undoubtedly
      influenced the selection of topics. It is fair to say that the authors were often
      surprised and certainly impressed with the overlapping interests and
      possibilities for collaboration among investigators of these two research areas.

PMID- 18626793
TI  - Implication of pituitary adenylate cyclase-activating polypeptide (PACAP) for
      neuroprotection of nicotinic acetylcholine receptor signaling in PC12 cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a
      neurotrophic factor through PAC1-R, PACAP-specific receptor, in the central
      nervous system. On the other hand, by interacting with nicotinic acetylcholine
      receptor (nAChR), nicotine exhibits several neuroprotective effects. Since the
      relevance of PACAP and nAChR signaling has not been reported so far, we attempted
      to investigate their relevance in terms of neuroprotection in PC12 cells.
      Regarding the effect of nicotine on PACAP gene expression, nicotine increased its
      mRNA level in time-dependent and dose-dependent manners in the PC12 cells
      differentiated with nerve growth factor (NGF). In addition, luciferase reporter
      assay demonstrated that nicotine treatment significantly augments the promoter
      activity of PACAP gene. Since PAC1-R mRNA expression was induced by NGF, PACAP
      exhibited neuroprotective effect against tunicamycin-induced cell death in the
      differentiated PC12 cells. Nicotine also exhibited the neuroprotective effect,
      which was significantly attenuated by Max.d.4 (PAC1-R specific antagonist). These
      results suggest that the increment of PACAP gene expression due to nicotine
      treatment might be involved in the neuroprotection by nicotine.

PMID- 18626794
TI  - Perinatal oxygen restriction does not result in reduced rat frontal cortex
      synaptophysin protein levels at adulthood as opposed to postmortem findings in
      schizophrenia.
AB  - Synaptophysin, a synaptic vesicle protein and a marker for synaptic density has
      been found to be reduced in postmortem prefrontal cortex of schizophrenia
      patients, consistent with evidence for synaptic deficits in schizophrenia. The
      contribution of both genetic and environmental factors to the etiology of
      schizophrenia is well established, and obstetric complications have been
      suggested as a non-genetic risk factor of schizophrenia. As there is only scarce
      evidence for a genetic linkage between synaptophysin's chromosomal locus
      (Xp11.22) and schizophrenia, we hypothesized that early neonatal exposure of rat
      pups to oxygen restriction would result in reduced frontal cortex synaptophysin
      protein levels at adulthood. We studied the effects of anoxia or hypoxia on 7-day
      old rats frontal cortex synaptophysin protein levels assessed by Western blotting
      4 and 7 weeks following the exposure. In hypoxia- or anoxia-exposed rats,
      synaptophysin protein levels were elevated both 4 and 7 weeks after the exposure.
      Two-way ANOVA followed by post hoc LSD analysis showed that the effect was
      predominantly at 4 weeks after exposure and that only anoxia-exposed rats
      differed significantly from control rats (p = 0.019). These results are in
      contrast to postmortem findings in schizophrenia and suggest that reduced
      synaptophysin protein levels in schizophrenia patients' postmortem brain do not
      result from perinatal oxygen deprivation.

PMID- 18626796
TI  - Fundamentals of optical imaging.
AB  - Optical imaging techniques offer simplistic while highly sensitive modalities for
      molecular imaging research. In this chapter, the major instrumental necessities
      for microscopic and whole-animal imaging techniques are introduced. Subsequently,
      the resulting imaging modalities using visible or near-infrared light are
      presented and discussed. The aim is to show the current capabilities and
      application fields of optics.

PMID- 18626797
TI  - Micro-CT.

PMID- 18626798
TI  - PET & SPECT instrumentation.
AB  - The nuclear medical imaging methods, positron emission tomography (PET) and
      single photon emission computed tomography (SPECT), utilize the detection of
      gamma rays leaving the body after a radioactive tracer has been administered. The
      sensitivity of PET allows the detection of picomolar tracer amounts in vivo and
      current technology offers millimeter (PET) or submillimeter (SPECT) spatial
      resolution. These techniques are used in clinical and preclinical applications.
      The basic principles of gamma ray detection and image generation in PET and SPECT
      are summarized in this chapter. Furthermore, effects causing degradation of image
      quality are discussed.

PMID- 18626795
TI  - Atypical p-ANCA in PSC and AIH: a hint toward a "leaky gut"?
AB  - Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are enigmatic
      chronic inflammatory diseases of the liver, which are frequently associated with
      chronic inflammatory bowel diseases. Both types of liver disease share various
      distinct autoantibodies such as atypical perinuclear antineutrophil cytoplasmic
      antibodies (p-ANCA), and thus are considered autoimmune disorders with atypical
      features. The discovery that atypical p-ANCA recognize both tubulin beta isoform
      5 in human neutrophils and the bacterial cell division protein FtsZ has renewed
      the discussion on the potential role of microorganisms in the pathogenesis of
      both diseases. In this paper, we review the evidence for microbial infection in
      PSC and AIH and discuss new concepts how cross-recognition between microbial
      antigens in the gut and host components by the immune system along with
      stimulation of pattern recognition receptors might give rise to chronic hepatic
      inflammatory disorders with features of autoimmunity.

PMID- 18626799
TI  - Magnetic resonance imaging and spectroscopy.
AB  - Magnetic resonance imaging (MRI) and spectroscopy (MRS) are noninvasive
      techniques that allow the characterization of morphology, physiology and
      metabolism in vivo. MRI and MRS have become techniques of choice in many pre
      clinical and clinical applications. In this chapter, the basic principles and the
      instrumentation of MRI and MRS are described. Furthermore, the factors that
      influence the sensitivity are discussed and examples for the limit of contrast
      agent detection are given.

PMID- 18626800
TI  - Ultrasound basics.
AB  - Imaging technologies for in vivo functional and molecular imaging in small
      animals have undergone a very fast development in the last years with very
      intense competition to further develop resolution and molecular sensitivity.
      Among the imaging technologies available, ultrasound-based molecular imaging
      methods are of particular interest, since the use of ultrasound contrast agents
      allows specific and sensitive depiction of molecular targets. Together with new
      developments in quantification methods of targeted microbubbles, sonography
      represents a dynamic and seminal tool for molecular imaging.

PMID- 18626801
TI  - Multimodal imaging approaches: PET/CT and PET/MRI.
AB  - Multimodality imaging, specifically PET/CT, brought a new perspective into the
      fields of clinical and preclinical imaging. Clinical cases have shown, that the
      combination of anatomical structures, revealed from CT, and the functional
      information from PET into one image, with high fusion accuracy, provides an
      advanced diagnostic tool and research platform. Although PET/CT is already an
      established clinical tool it still bears some limitations. A major drawback is
      that CT provides only limited soft tissue contrast and exposes the patient or
      animal, being studied, to a significant radiation dose. Since PET and CT scanner
      are hard-wired back to back and share a common patient bed, PET/CT does not allow
      simultaneous data acquisition. This temporal mismatch causes image artefacts by
      patient movement between the two scans or by respiration motion. To overcome
      these limitations, recent research concentrates on the combination of PET and MRI
      into one single machine. The goal of this development is to integrate the PET
      detectors into the MRI scanner which would allow simultaneous data acquisition,
      resulting in combined functional and morphological images with an excellent soft
      tissue contrast, very good spatial resolution of the anatomy and very accurate
      temporal and spatial image fusion. Additionally, since MRI provides also
      functional information such as blood oxygenation level dependant (BOLD) imaging
      or spectroscopy, PET/MRI could even provide multi-functional information of
      physiological processes in vivo. First experiments with PET/MRI prototypes showed
      very promising results, indicating its great potential for clinical and
      preclinical imaging.

PMID- 18626802
TI  - Contrast agents: magnetic resonance.
AB  - Even though the intrinsic magnetic resonance imaging (MRI) contrast is much more
      flexible than in other clinical imaging techniques, the diagnosis of several
      pathologies requires the involvement of contrast agents (CAs) that can enhance
      the difference between normal and diseased tissues by modifying their intrinsic
      parameters. MR CAs are indirect agents because they do not become visible by
      themselves as opposed to other imaging modalities. The signal enhancement
      produced by MRI CAs (i.e., the efficiency of the CAs) depends on their
      longitudinal (r1) and transverse (r2) relaxivity (expressed in s(-1) mmol(-1) 1),
      which is defined as the increase of the nuclear relaxation rate (the reciprocal
      of the relaxation time) of water protons produced by 1 mmol per liter of CA.
      Paramagnetic CAs (most of them complexes of gadolinium) are frequently used in
      clinics as extracellular, hepatobiliary or blood pool agents. Low molecular
      weight paramagnetic CAs have similar effects on R1 and R2, but the predominant
      effect at low doses is that of T1 shortening (and R1 enhancement). Thus, organs
      taking up such agents will become bright in a T1-weighted MRI sequence; these CAs
      are thus called positive contrast media. The CAs known as negative agents
      influence signal intensity mainly by shortening T2* and T2, which produces the
      darkening of the contrast-enhanced tissue. These CAs are generally composed of
      superparamagnetic nanoparticles, consisting of iron oxides (magnetite, Fe3O4,
      maghemite, gammaFe2O3, or other ferrites). Iron oxide nanoparticles are taken up
      by the monocyte-macrophage system, which explains their potential application as
      MRI markers of inflammatory and degenerative disorders. Most of the contemporary
      MRI CAs approved for clinical applications are non-specific for a particular
      pathology and report exclusively on the anatomy and the physiological status of
      various organs. A new generation of MRI CAs is progressively emerging in the
      current context of molecular imaging, agents that are designed to detect with a
      high specificity the cellular and molecular hallmarks of various pathologies.

PMID- 18626803
TI  - Contrast agents: X-ray contrast agents and molecular imaging--a contradiction?
AB  - It is the purpose of this article to discuss whether and how X-ray contrast media
      may contribute to molecular imaging. X-ray contrast media are small molecules
      containing heavy elements, preferentially iodine. Modern CT allows precise, fast
      and reliable quantification of contrast media concentrations in large volumes
      with excellent spatial resolution throughout the body. The main disadvantage is
      the low contrast sensitivity requiring iodine concentrations of > or =0.5 mg/ml.
      Various approaches of the past and the present to specific contrast agents
      reflecting physiological, cellular or molecular processes are presented and
      options for the future are discussed.

PMID- 18626804
TI  - Radiopharmaceuticals: molecular imaging using positron emission tomography.
AB  - We describe the use of molecules labeled with short-lived emitting radionuclides
      for molecular imaging in combination with the positron emission tomography
      technique. How to use molecular probes to visualize and quantitatively determine
      rates of specific biochemical events such as synaptic transmission, enzymatic
      processes and binding to specific receptor proteins is highlighted. The
      sensitivity of the PET technique and the ability to measure and validate
      relationships between molecular events and biological functions is a key factor
      for the successful application of PET in biomedical research. In specific
      applications, the opportunity of using molecules labeled in specific positions
      may be critical. Molecular imaging using PET is also gaining increasing interest
      as a tool in drug development, especially when applied to early proof of concept
      studies in man. In this chapter, the concept of molecular imaging is exemplified
      and the use of position-specific labeling of tracer molecules as a tool to gain
      understanding of complex biological processes will be discussed.

PMID- 18626805
TI  - Optical agents.
AB  - Optical imaging is an emerging modality in the growing field of biomedical
      diagnostics. The past decade has witnessed the development of a variety of
      promising strategies for optical imaging techniques. Fundamental to these
      techniques is the design and application of novel fluorescent markers to allow
      molecular level in-vivo studies of disease in animal models in the laboratory and
      eventually in human clinical studies. This review surveys the range of
      fluorophores employed in these probes and the alternative probe systems in which
      they are used: non-specific, targeted and activatable; recent developments in the
      area of fluorescent nanoprobes and multimodality constructs are also reviewed.

PMID- 18626806
TI  - Ultrasound contrast agents for molecular imaging.
AB  - The successful use of targeted ultrasound contrast agents (USCAs) for qualitative
      US-based imaging has been shown by several academic and industrial research
      groups in different animal models. Furthermore, techniques have been developed
      that enable the in-vivo quantification of targeted microbubbles (MBs). USCAs for
      quantitative functional and molecular imaging in small animals can be used for a
      more detailed characterization of new and established disease models and provide
      quantitative biological insights into the interaction between drug and target or
      target and disease in living animals. The advantages of such contrast agents in
      research and development are seen to be as follows: new functional or molecular
      findings in the complex biology of disease development, these findings can lead
      to new therapeutic strategies or drug candidates, a better understanding of the
      treatment effects of new and existing drug candidates, a more sensitive and
      specific characterization of early treatment effects in living animals,
      identification of in-vivo biomarkers for translational medicine. Further outcomes
      are seen in speeding up the evaluation of new drug compounds and in a reduction
      of the number of animals used for biomedical research.

PMID- 18626807
TI  - Agents for polarization enhancement in MRI.
AB  - The intrinsic low sensitivity of the NMR phenomenon can be overcome thanks to
      hyperpolarization procedures that break the limits of the Boltzmann equilibrium
      and may increase the NMR signal by a factor of 10(5). Hyperpolarization
      procedures have been applied to enhance the signal from noble gases, such as 3He
      and 129Xe, and small 13C-containing molecules. For the latter class, attention
      has been focused on the use of methods based on dynamic nuclear polarization
      (DNP) and para-hydrogen induced polarization (PHIP). After discussion of the
      basics of the methods, an overview of the main applications with 13C-containing
      molecules is presented. This includes pre-clinical MR investigations of vascular
      imaging, perfusion and catheter tracking as well as molecular imaging protocols
      that allow the development of highly innovative studies in the field of metabolic
      imaging.

PMID- 18626808
TI  - Acidic preparations of platelet concentrates release bone morphogenetic protein
      2.
AB  - BACKGROUND AND PURPOSE: Growth factors released from platelets have potent
      effects on fracture and wound healing. The acidic tide of wound healing, i.e. the
      pH within wounds and fractures, changes from acidic pH to neutral and alkaline pH
      as the healing process progresses. We investigated the influence of pH on lysed
      platelet concentrates regarding the release of growth factors. MATERIAL AND
      METHODS: Platelet concentrates free of leukocyte components were lysed and
      incubated in buffers with pH between 4.3 and 8.6. Bone morphogenetic protein-2
      (BMP-2), platelet-derived growth factor (PDGF), transforming growth factor
      beta(TGF-beta), and vascular endothelial growth factor (VEGF) were measured by
      quantitative enzyme-linked immunosorbent assays. RESULTS: PDGF, TGF-beta, and
      VEGF were present in all platelet preparations but the levels varied in a pH
      dependent fashion. BMP-2 was only detected in the most acidic preparation (pH
      4.3), which is interesting since BMP-2 has been reported to be an endogenous
      mediator of fracture repair and to be responsible for the initiation of fracture
      healing. INTERPRETATION: Our findings indicate that platelets release substantial
      amounts of BMP-2 only under conditions of low pH, the milieu associated with the
      critical initial stage of fracture healing.

PMID- 18626809
TI  - Negative effect of parecoxib on bone mineral during fracture healing in rats.
AB  - BACKGROUND AND PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are
      conventional cyclooxygen-ase (cox) inhibitors commonly used in musculoskeletal
      trauma to reduce the inflammatory response and pain, but they also seem to affect
      bone metabolism. Parecoxib is a cox inhibitor that selectively inhibits cox-2.
      Through their selective mechanism of action, these newer drugs are supposed to
      reduce the gastrointestinal side effects of conventional cox inhibitors. The
      effects on bone metabolism and healing have, however, not been fully elucidated.
      Thus, there are reasons for concern regarding the potential negative effects of
      these drugs on bone metabolism and bone repair. We investigated the effects of
      short-term administration of parecoxib on bone mineral formation and bone healing
      in rats. ANIMALS AND METHODS: 26 female Wistar rats were given parecoxib
      intraperitoneally for 7 days after a closed tibial fracture that was stabilized
      with an intra-medullary nail, and 26 animals were given saline. At 2, 3, and 6
      weeks after surgery bone mineral density (BMD) at the fracture site was measured
      using dualenergy X-ray absorptiometry (DEXA). 6 weeks after the fracture, 14 rats
      from the parecoxib group and 16 rats from the placebo group were killed for
      mechanical testing, and the rest of the animals were killed for tissue analysis.
      The healing fractures and the intact contralateral tibias were mechanically
      tested by three-point cantilever bending. RESULTS: The BMD at the fracture site
      was calculated as the average of the results after 2,3, and 6 weeks. Mean BMD was
      lower in the parecoxib group, 0.23 (SD 0.06) g/ cm2, than in the control group,
      0.27 (SD 0.05) g/cm2 (p = 0.01). There were no statistically significant
      differences in mechanical properties of the healing fractures after 6 weeks.
      However, the study may have lacked sufficient statistical power to determine
      whether a negative effect on healing had occurred. INTERPRETATION: No mechanical
      differences were detected between the control and treatment groups after 6 weeks,
      but they may have been present earlier in the fracture healing process. Our
      findings do, however, indicate that parecoxib given postoperatively for a week
      has a negative effect on mineralization during the early phase of fracture
      healing.

PMID- 18626810
TI  - Concentration of bone marrow aspirate for osteogenic repair using simple
      centrifugal methods.
AB  - Bone marrow transplantation can lead to osteogenic repair of intractable bone
      conditions. To achieve optimal clinical results, it is necessary to transplant as
      many cells with osteogenetic potential as possible. However, approaches involving
      special equipment and reagents for the extraction and purification of cells are
      expensive, and the complicated procedures involved are a hindrance to widespread
      acceptance of bone marrow transplantation for osteogenic repair. To standardize
      bone marrow transplantation for bone regeneration, a simple, safe, clean, and low
      cost system is required. We describe an easy-to-use method using a conventional
      manual blood bag centrifugation technique traditionally used for extracting buffy
      coats, for concentration of cells from bone marrow aspirates (BMAs) to obtain
      osteogenic progenitors.

PMID- 18626811
TI  - Fibrodysplasia ossificans progressiva: a new spotlight on an old disease-a case
      report.

PMID- 18626812
TI  - Adjacent segment degeneration: Time is not as important as facet preservation!

PMID- 18626813
TI  - Risk factors associated with acute hip prosthetic joint infections and outcome of
      treatment with a rifampin-based regimen.

PMID- 18626814
TI  - Th17 cells: a new therapeutic target in inflammatory dermatoses.
AB  - Th17 cells, named for their secretion of interleukin-17 (IL-17), are a new class
      of T-cells involved in a wide range of cutaneous autoimmune and inflammatory
      conditions. An overactive Th17 cell response in the skin can produce damaging
      results. There appears to be a partial role for the Th17 axis in the pathogenesis
      of a range of dermatological diseases including allergic contact dermatitis,
      atopic dermatitis, psoriasis, and scleroderma. Immunologists have also discovered
      a unique association between Th17 cells and cutaneous T-cell lymphoma. The Th17
      branch has been linked to a number of additional systemic inflammatory diseases
      with significant cutaneous pathology such as systemic lupus erythematosus,
      rheumatoid arthritis, inflammatory bowel disease, and Behcet's disease. Newly
      developed treatment modalities for neutralizing the Th17 branch of the immune
      system are proving to be valuable additions to the current therapeutic
      armamentarium.

PMID- 18626815
TI  - Volatile components from flower-heads of Centaurea nicaeensis All., C. parlatoris
      Helder and C. solstitialis L. ssp. schouwii (DC.) Dostal growing wild in southern
      Italy and their biological activity.
AB  - The volatile constituents of the flowerheads of Centaurea nicaeensis All., C.
      parlatoris Helder and C. solstitialis L. ssp. schouwii (DC.) Dostal were
      extracted by hydrodistillation and analysed by GC and GC-MS. Altogether 113
      components were identified. Fatty acids and hydrocarbons were the most abundant
      components in the oils. Caryophyllene and caryophyllene oxide were the main
      compounds of the sesquiterpene fraction. The study on the biological activity of
      the oils shows no significant activity.

PMID- 18626816
TI  - Volatile constituents of aerial parts of three endemic Centaurea species from
      Turkey: Centaurea amanicola Hub.-Mor., Centaurea consanguinea DC. and Centaurea
      ptosimopappa Hayek and their antibacterial activities.
AB  - The volatile constituents of the aerial parts of Centaurea amanicola Hub.-Mor.,
      Centaurea consanguinea DC. and Centaurea ptosimopappa Hayek were extracted by
      hydrodistillation and analysed by GC and GC-MS. Altogether 94 components were
      identified. Sesquiterpenoids, fatty acids and carbonylic compounds were the most
      abundant components in the oils. Hexadecanoic acid and (Z,Z )-9,12
      octadecadienoic acid were the main fatty acids in all the examined samples, that
      showed different patterns of composition. The study on the biological activity of
      the oils showed an action mainly against the Gram-positive pathogens.

PMID- 18626817
TI  - Volatile constituents of aerial parts of Centaurea sibthorpii (Sect.
      Carduiformes, Asteraceae) from Greece and their biological activity.
AB  - The volatile constituents of the aerial parts of Centaurea sibthorpii [Sect.
      Carduiformes, Asteraceae] collected in Greece were extracted by hydrodistillation
      and analysed by GC and GC-MS. Altogether 63 components were identified. Fatty
      acids and sesquiterpenoidic compounds were the most abundant components in the
      oil. A study on the biological activity of the oil showed no action against Gram
      positive and Gram-negative bacteria.

PMID- 18626818
TI  - Unequivocal NMR assignments: O-methoxy-methyl esters derivatives of acid
      chromanones from Calophyllum brasiliense CAMB. (Guanandi).
AB  - The present work describes the fractionation of the crude hexane extract (EBHEX)
      from Calophyllum brasiliense (Clusiaceae) stem bark. Derivatization of DCM(2-9)
      fraction with diazomethane afforded the chromanones inophylloidic acid,
      isobrasiliensic acid, as well as, a mixture containing isobrasiliensic and
      brasiliensic acids, in the form of their more stable O-methoxy-methyl esters
      derivatives 1, 2, and 3, respectively. The isolation of 1 from C. brasiliense is
      described for the first time herein. The use of two-dimensional NMR methods ((1)H
      COSY, HMQC, and HMBC) allowed the precise determination of (13)C and (1)H
      chemical shifts of compounds 1, 2, and 3.

PMID- 18626819
TI  - Synthesis and crystal structure of maleopimaric acid.
AB  - The title compound maleopimaric acid was synthesized by a Diels-Alder reaction
      between maleic anhydride and Pinus elliottii engelm oleoresin at room temperature
      and it was characterized by single crystal X-ray diffraction. The white crystals
      crystallized in the orthorhombic system, space group P2(12121) with cell
      dimensions: a = 7.6960 (15) A, b = 11.851 (2) A, c = 24.577 (5) A, alpha = 90
      degrees, beta = 90 degrees, gamma = 90 degrees, V = 2241.6(8) A(3), and R(1) =
      0.0716, wR(2) = 0.1975. The two fused and unbridged cyclohexane rings form a
      trans ring junction with chair conformation with two methyl groups in axis
      positions, the anhydride ring is planar. Crystal water existed in the molecular
      and stabilized the structure through intermolecular hydrogen bonds.

PMID- 18626820
TI  - A new ent-kauranoid from Isodon lophanthoides var. geradianus.
AB  - A new ent-kaurane diterpenoid, lophanthodin G (1) and one known abietanoid,
      6alpha-hydroxyferruginol (2), were isolated from the leaves of Isodon
      lophanthoides var. geradianus. The structure of the new compound 1 was
      established using spectroscopic methods including extensive 1D and 2D NMR
      analysis.

PMID- 18626821
TI  - Naturally occurring esterification reactions with bryostatin.
AB  - Bryostatin structures share a commonality of a central bryophan ring, but each
      differs due to two groups (R(1) and R(2)) that are attached to the bryophan ring
      via ester bonds. This research examines the impact that conditions such as UV
      light, acidic and basic conditions can have on the bryostatin structure in the
      presence of octanoic acid and water. Mass spectrometry (MS) measurements suggest
      that bryostatin can easily rearrange into various structures under natural
      conditions by reacting with carboxylates that are ubiquitous in nature. A second
      set of measurements suggest bryostatin can be hydrolyzed by water, a reaction
      that has significant implications in both medicinal applications and extraction
      procedures.

PMID- 18626822
TI  - Sesquiterpenes from Culcasia scandens P. Beauv.
AB  - From Culcasia scandens P. Beauv., carota-4(5), 11(12)-diene (isodaucene), carota
      3(4), 11(12)-dien-5-one, a new epoxide, 4,5-epoxy-carota-11(12)-ene (isodaucene
      epoxide) and beta-caryophyllene epoxide were isolated. The structures were
      established spectroscopically. Epoxidation of isodaucene with m-CPBA confirmed
      the structure and stereochemistry of the new epoxide.

PMID- 18626823
TI  - Pregnane glycosides and steroid saponins from Smilax bockii Warb. and their NGF
      potentiating activity.
AB  - The chemical constituents of the roots of Smilax bockii Warb. were investigated
      and two pregnane glycosides and three steroid saponins were isolated. Their
      structures were established as 3beta-hydroxypregna-5,16-dien-20-one-3-O-alpha-L
      rhamnopyranosyl(1 --> 4)-alpha-L-rhamnopyranosyl(1 --> 4)-[alpha-L
      rhamnopyranosyl(1 --> 2)]-beta-D-glucopyranoside (1), 3beta-hydroxypregna-5,16
      dien-20-one-3-O-alpha-L-rhamnopyranosyl(1 --> 2)-[alpha-L-rhamnopyranosyl(1 -->
      4)]-beta-D-glucopyranoside (2), dioscin (3), methyl protodioscin (4), 26-O-beta-D
      glucopyranosyl-22alpha-methoxyl-(25R)-furost-5-en-3beta, 26-diol 3-O-alpha-L
      rhamnopyranosyl(1 --> 4)-alpha-L-rhamnopyranosyl(1 --> 4)-[alpha-L
      rhamnopyranosyl(1 --> 2)]-beta-D-glucopyranoside (5) on the basis of spectral
      analysis and chemical methods. Compound 1 is a new natural product and compounds
      2, 5 were first isolated from the genus Smilax. Compound 5 showed enhancing
      activity of nerve growth factor (NGF)-induced neurite outgrowth in PC 12D cells.

PMID- 18626824
TI  - The green approaches for the synthesis of N-dehydroabietic alpha
      aminophosphonates.
AB  - Three kinds of O,O-diethyl N-dehydroabietic aminoarylmethylphosphonates were
      synthesized from natural product derivatives by two steps of solvent-free
      reactions through imines intermediates and their structures were characterized by
      IR, (1)H NMR and (31)P NMR spectroscopy. The solvent-free reactions afforded good
      yields of N-dehydroabietic imines and alpha-aminophosphonates although the strong
      space block of dehydroabietylamine to amino group. The green approaches resulted
      negligible waste and the reactions were environment friendly without using
      noxious solvents.

PMID- 18626825
TI  - A new 5,11-epoxymegastigmane glucoside from Acanthus ilicifolius.
AB  - From a China mangrove plant Acanthus ilicifolius Linn., a new compound, 5,11
      epoxymegastigmane glucoside (1) was isolated along with one known compound of
      megastigmane glucosides, (6S, 9S)-roseoside (2). The structure of compound 1 was
      determined on the basis of 1D- and 2D-NMR techniques (DEPT, COSY, HMBC, HMQC,
      NOESY) and HR-FABMS. The structure of 1 was established as (1S, 3S, 5R, 6R, 7E)
      5,11-epoxy-3-hydroxymegastigman-7-en-9-one-3-O-beta-D-glucopyranoside.

PMID- 18626826
TI  - Ergosta-4,6,8(14),22-tetraen-3-one from Vietnamese Xylaria sp. possessing
      inhibitory activity of nitric oxide production.
AB  - From the methanolic extract of Xylaria sp. collected in Vietnam, a fluorescent
      constituent, ergosta-4,6,8(14),22-tetraen-3-one (1) was isolated and elucidated
      by the combination of 2D NMR, high resolution MS, IR and UV spectroscopy. Its
      inhibitory activity of nitric oxide production in RAW 264.7 cells stimulated by
      lipopolysaccharide was examined and showed a potential activity with the IC(50)
      value of 28.96 microM.

PMID- 18626827
TI  - Irregular linear sesquiterpene dilactones from Anthemis auriculata Boiss.
AB  - Seven new irregular linear sesquiterpene lactones, epi-antheindurolide A (1), epi
      antheindurolide A-5,6-oxide (2), 5-hydroxy-5,6-dihydro-6,13-dehydro-epi
      antheinduro lide A (3), 5-hydroperoxy-5,6-dihydro-6,13-dehydro-epi
      antheindurolide A (4), epi-antheindurolide B (5), 6-hydroxy-5,6-dihydro-4,5
      dehydro-epi-antheindurolide A (6) and 6-hydroperoxy-5,6-dihydro-4,5-dehydro-epi
      antheindurolide A (7), were isolated from the flowers of Anthemis auriculata
      Bioss. Their structures were established by spectroscopic techniques. The
      discussed compounds were found to be stereoisomers of recently reported lactones
      for A. arvensis.

PMID- 18626828
TI  - Bisbenzopyrans and alkaloids from the roots of Stemona cochinchinensis.
AB  - Two new bisbenzopyrans, namely 3,3'-bis(3,4-dihydro-4-hydroxy-6,8-dimethoxy-2H-1
      benzopyran) (1), and 8'-methoxy-3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1
      benzopyran) (2), together with known 3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H
      1-benzopyran) (3), as well as three known pyrido[1,2-alpha]azapine alkaloids,
      stemokerrin (4), oxystemokerrin (5) and oxystemokerrin-N-oxide (6), were isolated
      and identified from the roots of Stemona cochinchinensis. The structures of these
      compounds were elucidated by 1D- and 2D-NMR spectra and other spectroscopic
      studies.

PMID- 18626829
TI  - Pre-hospital delay of treatment in patients with ST segment elevation myocardial
      infarction undergoing primary percutaneous coronary intervention: experience of
      cardiac centre located in the vicinity of the centre of Warsaw.
AB  - BACKGROUND: Early reperfusion therapy with primary percutaneous coronary
      intervention (PCI) in patients with ST-segment elevation myocardial infarction
      (STEMI) improves left ventricular function and reduces mortality. AIM: To assess
      the time delay in treatment of patients with STEMI referred to a twenty-four-hour
      interventional centre located in the vicinity of the centre of Warsaw. METHODS:
      We analysed 350 consecutive STEMI patients admitted to our Department between
      October 2005 and September 2006. The majority of the patients - 244 (69.7%), were
      admitted via hospitals without an interventional department. Sixty-two (17.7%)
      patients were transported directly by ambulance from home, 34 (9.7%) from a
      community health centre and 10 patients (2.9%) came by themselves from home or
      work. A detailed interview concerning the time of symptom onset was conducted in
      342 patients (97.7%). RESULTS: Sixty-two (18%) patients arrived at the
      interventional centre within the first 2 hours from symptom onset: 6 women (5.5%
      of all women in the study population) and 56 (24.1%) men (p <0.0001). Within the
      first 2 hours, 32 (13.1%) patients were admitted via another hospital and 20
      (32.2%) directly by ambulance (p <0.001). During the first 7 days of
      hospitalisation the following patients died: 2 (3.2%) patients admitted within
      the first 2 hours via another hospital, 6 (3.4%) patients among 178 admitted
      between 2 and 6 hours after pain onset, 4 (8.3%) among 48 admitted between 6 and
      12 hours and 8 (14.8%) among 54 patients with the pain duration over 12 hours (p
      <0.02). During the first 7 days of hospitalisation 8 (3.3%) patients admitted
      within the first 6 hours after pain onset died compared with 12 (11.8%) admitted
      later (p <0.003). CONCLUSIONS: In the interventional centre located near the
      centre of Warsaw symptom-onset-to-door time was 120 minutes only in 18% of
      patients with STEMI. Almost 70% of patients underwent interhospital transfer for
      primary PCI. Prolongation of the time from onset of symptoms to successful PCI
      worsened prognosis. When transporting patients with acute coronary syndrome,
      efforts should be made to avoid district hospitals without a catheterisation
      laboratory. Direct transportation by ambulance or helicopter with educated staff
      equipped with ECG teletransmission data, which may substantially shorten time to
      treatment, should be preferred.

PMID- 18626830
TI  - Effects of early abciximab administration before primary percutaneous coronary
      intervention on left ventricular function assessed by cardiac magnetic resonance.
AB  - BACKGROUND: It has been shown that early abciximab administration before primary
      percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial
      infarction (STEMI) improves efficacy of treatment. However, there are no data on
      the impact of this strategy on left ventricular (LV) function during long-term
      follow-up. AIM: To analyse the effects of early abciximab administration in
      patients with first anterior STEMI treated with pPCI on infarct size and LV
      function assessed by cardiac magnetic resonance. METHODS: A total of 59 patients
      with STEMI, <12 hours from the chest pain onset, without cardiogenic shock,
      admitted to local hospitals without interventional facilities, with anticipated
      delay to pPCI <90 min were randomly assigned to two study groups: 27 patients
      received abciximab before transfer to the catheterisation laboratory (early
      abciximab group), and 32 patients received abciximab in the catheterisation
      laboratory just before pPCI (late abciximab group). All patients received aspirin
      and heparin (70 U/kg) before transfer to the cath lab. Clopidogrel loading dose
      was administered in the cath lab before angiography. RESULTS: Cardiac magnetic
      resonance was performed in 14 patients from each study group 1 year after pPCI
      and revealed a significantly lower LV end-systolic volume index (p=0.003), end
      diastolic volume index (p=0.009) and better ejection fraction (p <0.05) in
      patients who received abciximab early. CONCLUSIONS: Early abciximab
      administration prior to transfer for pPCI in patients with first anterior STEMI
      results in a lower degree of LV remodelling and better LV ejection fraction at 1
      year follow-up compared to late abciximab administration in the cath lab during
      pPCI.

PMID- 18626831
TI  - The LocaLisa system as the key to shortening the procedure duration and
      fluoroscopy time during ablation of atrial fibrillation.
AB  - BACKGROUND: Ablation of atrial fibrillation (AF) can be difficult and time
      consuming. Systems facilitating catheter navigation may be helpful. AIM: To
      compare the efficacy of the LocaLisa system with the conventional
      mapping/ablation approach to radiofrequency (RF) ablation of AF. METHODS: Group
      1, consisting of 64 patients (48 male; aged 51.5+/-10.6 years), underwent
      segmental isolation of the pulmonary veins with the Lasso catheter and the
      LocaLisa system. Group 2, consisting of 64 patients (44 male, aged 51.4+/-11.0
      years), had RF ablation guided by means of a conventional fluoroscopy-based
      approach. Clinical and procedural data were analysed. RESULTS: Nine patients from
      group 1 and three patients from group 2 had persistent AF. In group 1 the mean
      number of isolated veins was 3.98+/-0.96, while in group 2 - 4.0+/-0.95 (NS). In
      group 1 cavotricuspid isthmus lines were created in four patients and lines in
      the roof of the left atrium in two patients. One patient needed slow pathway
      ablation. In group 2 six patients had ablation of the cavotricuspid isthmus and a
      line was created at the roof of the left atrium in one patient. Two patients had
      ectopic activity ablated in the crista terminalis. Procedure times were 131.6+/
      40.3 and 170.0+/-56.5 min (p <0.0001) and fluoroscopy times were 16.93+/-9.7 and
      35.66+/-12.7 min (p <0.0001) for groups 1 and 2, respectively. Long-term efficacy
      of RF ablation was similar in both groups (for example, complete success was
      achieved in 59% of patients using LocaLisa and 50% without using this system,
      NS). CONCLUSIONS: The LocaLisa navigation system makes it possible to shorten
      both the duration of the procedure and the total fluoroscopy time during ablation
      of AF.

PMID- 18626832
TI  - Gender differences and in-hospital mortality in patients undergoing percutaneous
      coronary interventions.
AB  - BACKGROUND: Many observational and randomised studies have suggested that women
      are referred for invasive diagnostics and treatment of coronary artery disease
      (CAD) less frequently than men, and the effects of percutaneous coronary
      intervention (PCI) among women are worse than in men. AIM: To compare direct
      results of PCI in men and women. METHODS: The study was a retrospective
      assessment of case records of one thousand consecutive patients treated with PCI
      because of acute myocardial infarction (AMI) (344 patients), unstable angina (UA)
      (164 patients) and stable angina (SA) (492 patients). We examined the effects of
      demographic, angiographic and clinical variables on the duration of
      hospitalisation and in-hospital mortality separately in men and in women.
      RESULTS: Women constituted 30.7% of patients treated with PCI because of AMI,
      39.6% of those with UA and just 25.8% of those with SA. Women were significantly
      older than men, had a higher BMI, and more often suffered from hypertension and
      diabetes. The duration of hospitalisation was the same in men and women if the
      reason for PCI was SA or UA, however, in case of AMI women were hospitalised
      significantly longer than men. In the univariate analysis gender had no influence
      on in-hospital mortality regardless of the reason for PCI treatment. Among the
      variables subjected to multivariate analysis female gender, age, BMI, diabetes,
      hypercholesterolaemia, indication for PCI, final TIMI flow in the target vessel
      and cardiogenic shock as a complication of AMI were shown to affect mortality.
      Significant effects on in-hospital mortality for women were exhibited only by
      cardiogenic shock. Among men, indication for PCI, age, diabetes and final TIMI
      flow in the target vessel also had a significant influence on in-hospital
      mortality. CONCLUSIONS: Stable angina is a reason for performing PCI more rarely
      in women than in men. Women with CAD are older than men and have more risk
      factors. The in-hospital mortality among patients treated with PCI because of SA
      is independent of gender. Cardiogenic shock appeared to be the only factor that
      influences in-hospital mortality in women. In the case of men such an influence
      is also observed for indication for PCI (AMI, UA or SA), diabetes and final TIMI
      flow in the target vessel.

PMID- 18626834
TI  - [Implantation of the Figulla Occlutech device in a patient with an ostium
      secundum atrial septal defect].
AB  - A case of a 50 year old female with a secundum atrial septal defect is described.
      The patient underwent successful implantation of a new occluder - Figulla
      Occlutech device. Differences in the types of occluders used for this purpose are
      discussed.

PMID- 18626833
TI  - Pharmacotherapy in patients with stable coronary artery disease treated on an
      outpatient basis in Poland. Results of the multicentre RECENT study.
AB  - BACKGROUND: Comprehension of therapeutic methods in patients with stable coronary
      artery disease (CAD) is mandatory for the introduction of successful prevention.
      AIM: To gather information regarding individuals with stable coronary artery
      disease treated by specialists and general practitioners on an outpatient basis.
      METHODS: A representative group of 215 general practitioners and 67 specialists
      participated in this study. The analysis contains data concerning pharmacotherapy
      in a group of 2,593 patients with stable CAD (mean age - 65.0+/-9.8 years, women 
      44.6%). RESULTS: The patients received the following treatment: acetylsalicylic
      acid - 75.3%, other antiplatelet drugs - 6.6% (antiplatelet drugs altogether -
      81.9%), beta-blockers - 81.1%, ACE-I - 78.8%, statins - 71.9%, fibrates - 4.7%,
      long-acting nitrates - 53.0%, short--acting nitrates - 33.1%, molsidomine -
      18.2%, calcium channel blockers - 23.8%, metabolic drugs (trimetazidine) - 13.4%,
      diuretics - 43.5%, and angiotensin receptor antagonists - 1.7% of patients. Drugs
      classified as non-cardiological were received by 36.2% of patients. The optimal
      pharmacotherapy including four medications, one from each therapeutic class used
      in order to improve the prognosis of the patient (an antiplatelet drug, a beta
      blocker, an ACE-I, statin), was received by a total of 45.8% of the participants,
      three medications by 31.7%, two medications by 15.8%, and one medication by 5.5%;
      1.2% of the participants did not receive any medication from the four groups of
      drugs improving prognosis. What is worth noting, however, is the use of
      relatively small doses of ACE-I and beta-blockers. 69.9% of patients also
      received at least one symptomatic drug (a long-acting nitrate, a calcium channel
      blocker, a metabolic drug, molsidomine), including 39.7% - 1 drug, 22.7% - 2
      drugs, 6.7% - 3 drugs, and 0.8% - 4 drugs from the classes mentioned above.
      CONCLUSIONS: The results of the RECENT study indicate that great progress has
      been made in the pharmacotherapy of CAD in Poland within the last few years.
      Currently, the majority of patients receive drugs that improve prognosis. The
      awareness of the benefits of the use of combined treatment with all the drug
      groups and their appropriate doses should be higher. The significant percentage
      of patients with persisting symptoms of angina pectoris indicates the necessity
      to improve the efficacy of intervention also in this respect.

PMID- 18626835
TI  - [Left atrial myxoma in a patient with heart failure after myocardial infarction -
      a case report].
AB  - A case of a 54-year-old male patient with left atrial myxoma, coronary heart
      disease, heart failure and multiple cardiovascular risk factors is described. The
      patient did not present typical symptoms of myxoma. Diagnosis and treatment of
      cardiac myxoma as well as the importance of echocardiographic examination in
      every patient with decompensated chronic heart failure are discussed.

PMID- 18626836
TI  - [Patient with purulent pericarditis caused by Salmonella enteritidis complicated
      by tamponade].
AB  - We report a case of a 64-year-old male patient with a history of advanced chronic
      heart failure, who was admitted to our hospital with symptoms of decompensated
      right heart failure. Chronic tamponade was diagnosed and conservative treatment
      was administered. Due to the lack of improvement, surgical drainage of the
      pericardial sack was performed and Salmonella enteritidis was cultured from the
      pericardial fluid. After a month the patient fully recovered and was discharged.

PMID- 18626838
TI  - [Left ventricular assist device - unexpected benefits for the failing heart].

PMID- 18626837
TI  - [Thrombus in transit - two cases of patients with massive pulmonary embolism
      treated with thrombolysis].
AB  - Two cases of large, free-floating right heart thrombi in patients with massive
      pulmonary embolism and a history of deep vein thrombosis are presented. In a 30
      year-old male with prominent obesity and a history of hypertension, disappearance
      of the thrombus at the end of alteplase infusion coexisted with onset of
      haemodynamic stabilization. In a 70-year-old female, the thrombus, which
      persisted despite streptokinase administration, translocated suddenly (during
      echocardiography) to the pulmonary artery, which resulted in a deterioration in
      her status. After alteplase administration following heparin infusion, steady
      clinical and echocardiographic improvement was observed.

PMID- 18626839
TI  - [Cardiac rehabilitation in the elderly].

PMID- 18626840
TI  - [Electrocardiogram in Fabry's disease].

PMID- 18626841
TI  - [Pulmonary artery aneurysm with severe pulmonary regurgitation in a mildly
      symptomatic patient with tetralogy of Fallot].

PMID- 18626842
TI  - [Late in-stent thrombosis as a cause of acute coronary syndrome complicated by
      out-of-hospital cardiac arrest].

PMID- 18626843
TI  - [Successful RF ablation of permanent VT in a patient with acute coronary syndrome
      treated by complex angioplasty and stent implantation].
AB  - We describe a case of a 59-year-old male with permanent VT in the course of an
      acute coronary syndrome. Coronary angiography revealed acute occlusion of the
      right coronary artery. Although the underlying condition was treated by
      implantation of 4 stents with excellent haemodynamic effect (TIMI 3), the
      tachycardia continued, being refractory to drugs (amiodarone). The attempts to
      restore sinus rhythm by DC electrical cardioversion or transvenous pacing were
      unsuccessful. The patient was referred to the EP lab. A critical isthmus
      localised at the paraseptal region of the LV and parallel to the mitral annulus
      was identified. The isthmus was closed by linear RF application, resulting in VT
      termination. Due to impaired LV ejection fraction (<30%) the patient was
      scheduled for ICD implantation. During 6-week follow-up the patient remained free
      of arrhythmia.

PMID- 18626845
TI  - [Fallot, Blalock and Taussig - the 'blue babies' odyssey].
AB  - 120 years ago, Louis Fallot described a congenital heart malformation consisted
      of a special constellation. This was a cyanotic malformation, hence the term 'the
      blue baby syndrome'. In 1949 there was a first trial of correction of tetralogy
      of Fallot by joining pulmomary artery with subclavial artery. This vessels
      connection was fixed in medical terminology as Blalock-Taussig shunt.

PMID- 18626846
TI  - [Attachment and development within psychosomatic medicine].

PMID- 18626844
TI  - [Diagnosis-related patient groups].

PMID- 18626847
TI  - [Evidence-based psychotherapy of depressive disorders: acute therapy and
      maintenance therapy].

PMID- 18626848
TI  - [Introduction of a balanced scorecard in a social psychiatric outpatient clinic].

PMID- 18626849
TI  - [Caspar Kulenkampff (1922-2002)].

PMID- 18626850
TI  - [Thesis from the workgroup prevention of violence and compulsion on current
      developments in psychiatric hospitals].

PMID- 18626851
TI  - [Reply to Lubenau's description of ECT from the patient's perspective. Psychiat
      Prax 2008; 35: 48-49].

PMID- 18626853
TI  - Mental Adjustment to Cancer Scale: psychometric properties in a large cancer
      cohort.
AB  - OBJECTIVES: The Mental Adjustment to Cancer (MAC) Scale is widely used to assess
      psychological response to cancer. There have been several attempts to replicate
      independently the original factor structure of the MAC. Evidence from these
      replication studies is reviewed. A re-analysis of the MAC Scale was conducted on
      a substantial new cohort in order to clarify the factor structure. METHODS: 1255
      patients with various cancer diagnoses completed the MAC Scale. RESULTS: Two
      results emerged: first, that the original MAC dimension of
      Helplessness/Hopelessness is extremely stable and robust; second, that the
      original factors can be subsumed within two overarching (first order) factors
      relating to positive and negative adjustment scores. CONCLUSIONS: The original
      MAC Scale remains a satisfactory measure of psychological outcome. Two-higher
      order factors representing global adjustment are now available to provide an
      overall summary measure alongside the original specific sub-scales.

PMID- 18626855
TI  - The application of membrane biological reactors for the treatment of wastewaters.
AB  - Combining membrane technology with biological reactors for the treatment of
      municipal and industrial wastewaters has led to the development of three generic
      membrane processes within bioreactors: for separation and recycle of solids; for
      bubbleless aeration of the bioreactor; and for extraction of priority organic
      pollutants from hostile industrial wastewaters. Commercial aerobic and anaerobic
      membrane separation bioreactors already provide a small footprint alternative to
      conventional biological treatment methods, producing a high-quality effluent at
      high organic loading rates. Both the bubbleless aeration and extractive membrane
      bioreactors are in the development stages. The former uses gas-permeable
      membranes to improve the mass transfer of oxygen to the bioreactor by providing
      bubbleless oxygen. By using a silicone membrane process, extractive membrane
      bioreactors transfer organic pollutants from chemically hostile wastewaters to a
      nutrient medium for subsequent biodegradation. All three membrane bioreactor
      (MBR) processes are comparatively and critically reviewed. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18626856
TI  - Long-term impact of dissolved O(2) on the activity of anaerobic granules.
AB  - The impact of influent dissolved O(2) on the characteristics of anaerobic
      granular sludge was investigated at various dissolved O(2) concentrations (0.5
      8.1 ppm) in 1- and 5-L laboratory-scale upflow anaerobic sludge bed (UASB)-like
      anaerobic/aerobic coupled reactors with a synthetic wastewater (carbon sources
      containing 75% sucrose and 25% acetate). The rate of dissolved O(2) supplied to
      the coupled reactor was as high as 0.40 g O(2)/L(rx).d, and the anaerobic/aerobic
      coupled reactors maintained excellent methanogenic performances at a COD loading
      rate of 3 g COD/L(rx).d even after the reactors had been operated with dissolved
      O(2) for 3 months. The activities of granular sludge on various substrates
      (glucose, propionate, and hydrogen) were not impaired, and acetate activity was
      even improved over a short term. However, after 3 months of operation, slight
      declines on the acetoclastic activities of granules were observed in the coupled
      reactor receiving the recirculated fluid containing 8.1 ppm dissolved
      O(2).Methane yield in the anaerobic control reactor and anaerobic/aerobic coupled
      reactors revealed that a significant aerobic elimination (up to 30%) of substrate
      occurred in the coupled reactors, as expected. The presence of dissolved O(2) in
      the recirculated fluid resulted in the development of fluffy biolayers on the
      granule surface, which imposed a negative impact on the settleability of granular
      sludge and caused a slightly higher sludge washout. This research shows that the
      anaerobic/aerobic coupled reactor can be successfully operated under O(2)-limited
      conditions and is an ideal engineered ecosystem integrating oxic and anaerobic
      niches. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626857
TI  - High-cell-density cultivation of yeasts on disaccharides in oxygen-limited batch
      cultures.
AB  - Many facultatively fermentative yeast species exhibit a "Kluyver effect": even
      under oxygen-limited growth conditions, certain disaccharides that support
      aerobic, respiratory growth are not fermented, even though the component
      monosaccharides are good fermentation substrates. This article investigates the
      applicability of this phenomenon for high-cell-density cultivation of yeasts. In
      glucose-grown batch cultures of Candida utilis CBS 621, the onset of oxygen
      limitation led to alcoholic fermentation and, consequently, a decrease of the
      biomass yield on sugar. In maltose-grown cultures, alcoholic fermentation did not
      occur and oxygen-limited growth resulted in high biomass concentrations (90 g dry
      weight L(-1) from 200 g L(-1) maltose monohydrate in a simple batch
      fermentation). It was subsequently investigated whether this principle could also
      be applied to Kluyveromyces species exhibiting a Kluyver effect for lactose. In
      oxygen-limited, glucose-grown chemostat cultures of K. wickerhamii CBS 2745, high
      ethanol concentrations and low biomass yields were observed. Conversely, ethanol
      was absent and biomass yields on sugar were high in oxygen-limited chemostat
      cultures grown on lactose. Batch cultures of K. wickerhamii grown on lactose
      exhibited the same growth characteristics as the maltose-grown C. utilis
      cultures: absence of ethanol formation and high biomass yields. Within the
      species K. marxianus, the occurrence of a Kluyver effect for lactose is known to
      be strain dependent. Thus, K. marxianus CBS 7894 could be grown to high biomass
      densities in lactose-grown batch cultures, whereas strain CBS 5795 produced
      ethanol after the onset of oxygen limitation and, consequently, yielded low
      amounts of biomass. Because the use of yeast strains exhibiting a Kluyver effect
      obviates the need for controlled substrate-feeding strategies to avoid oxygen
      limitation, such strains should be excellently suited for the production of
      biomass and growth-related products from low-cost disaccharide-containing
      feedstocks. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626858
TI  - Metal biosorption equilibria in a ternary system.
AB  - Equilibrium metal uptake performance of a biosorbent prepared from Ascophyllum
      nodosum seaweed biomass was studied using aqueous solutions containing copper,
      cadmium, and zinc ions in binary and ternary mixtures. Triangular equilibrium
      diagrams can graphically represent all the ternary equilibrium sorption data.
      Application of the multicomponent Langmuir model to describe the three-metal
      system revealed its nonideal characteristics, whereby the value of apparent
      dissociation constants for the respective metals differed for each system. This
      restricted the prediction of the ternary equilibria from the binary systems.
      However, some predictions of the ternary system behavior from the model were
      consistent with experimental data and with conclusions postulated from the three
      possible binary subsystems. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626859
TI  - Lysine production from methanol at 50 degrees C using Bacillus methanolicus:
      Modeling volume control, lysine concentration, and productivity using a three
      phase continuous simulation.
AB  - A simulation was developed based on experimental data obtained in a 14-L reactor
      to predict the growth and L-lysine accumulation kinetics, and change in volume of
      a large-scale (250-m(3)) Bacillus methanolicus methanol-based process. Homoserine
      auxotrophs of B. methanolicus MGA3 are unique methylotrophs because of the
      ability to secrete lysine during aerobic growth and threonine starvation at 50
      degrees C. Dissolved methanol (100 mM), pH, dissolved oxygen tension (0.063 atm),
      and threonine levels were controlled to obtain threonine-limited conditions and
      high-cell density (25 g dry cell weight/L) in a 14-L reactor. As a fed-batch
      process, the additions of neat methanol (fed on demand), threonine, and other
      nutrients cause the volume of the fermentation to increase and the final lysine
      concentration to decrease. In addition, water produced as a result of methanol
      metabolism contributes to the increase in the volume of the reactor. A three
      phase approach was used to predict the rate of change of culture volume based on
      carbon dioxide production and methanol consumption. This model was used for the
      evaluation of volume control strategies to optimize lysine productivity. A
      constant volume reactor process with variable feeding and continuous removal of
      broth and cells (VF(cstr)) resulted in higher lysine productivity than a fed
      batch process without volume control. This model predicts the variation in
      productivity of lysine with changes in growth and in specific lysine
      productivity. Simple modifications of the model allows one to investigate other
      high-lysine-secreting strains with different growth and lysine productivity
      characteristics. Strain NOA2#13A5-2 which secretes lysine and other end-products
      were modeled using both growth and non-growth-associated lysine productivity. A
      modified version of this model was used to simulate the change in culture volume
      of another L-lysine producing mutant (NOA2#13A52-8A66) with reduced secretion of
      end-products. The modified simulation indicated that growth-associated production
      dominates in strain NOA2#13A52-8A66. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626860
TI  - Catalytic durability of magnetoproteoliposomes captured by high-gradient magnetic
      forces in a miniature fixed-bed reactor.
AB  - Cytochrome c-oxidase, used as a model membrane-bound enzyme, was embedded in
      phospholipid bilayer membranes, attached to nanometer-sized Fe(3)O(4) colloids
      (so-called magnetoliposomes). In comparison with the lipid-depleted free enzyme,
      both the activity and the enzymatic stability of the complexes, stored at 4
      degrees C, were considerably enhanced. These beneficial properties of
      magnetoproteoliposomes have been successfully exploited in a magnetically
      controlled fixed-bed bioreactor, operating in a continuous flow regime. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18626861
TI  - Low multiplicity infection of insect cells with a recombinant baculovirus: The
      cell yield concept.
AB  - In vitro infection of insect cells with baculoviruses is increasingly considered
      a viable means for the production of biopesticides, recombinant veterinary
      vaccines, and other recombinant products. Batch fermentation processes
      traditionally employ intermediate to high multiplicities of infection
      necessitating two parallel scale-up processes-one for cells and one for virus. In
      this study, we consider the use of multiplicities of infection as low as 0.0001
      plaque-forming units per cell, a virus level low enough to enable infection of
      even large reactors (e.g., 10 m(3)) directly from a frozen stock. Using low
      multiplicities in the Sf9/beta-gal-AcNPV system, recombinant protein titers
      comparable with the maximum titer observed in high multiplicity infections were
      achieved. Cultures yielding the maximum titer were characterized by reaching a
      maximum cell density between 3 and 4 x 10(9) cell L(-1). This optimal cell yield
      did not depend on the multiplicity of infection, supporting the existing view
      that batch cultures are limited by availability of substrate. Up to a certain
      cell density, product titer will increase almost linearly with availability of
      biocatalyst, that is, cells. Beyond this point any further cell formation comes
      at the expense of final product titer. Low multiplicity infections were found not
      to cause any significant dispersion of the protein production process. Hence,
      product stability is not a major issue of concern using low multiplicities of
      infection. The sensitivity to initial conditions and disturbances, however,
      remains an issue of concern for the commercial use of low multiplicity
      infections. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626862
TI  - Effect of gene amplification on threonine production by yeast.
AB  - In this work, we have studied the effect of amplifying different alleles involved
      in the threonine biosynthesis on the amino acid production by Saccharomyces
      cerevisiae. The genes used were wild-type HOM3, HOM2, HOM6, THR1, and THR4, and
      two mutant alleles of HOM3 (namely HOM3-R2 and HOM3-R6), that code for feedback
      insensitive aspartate kinases. The results show that only the amplification of
      the HOM3 alleles leads to threonine and, in some instances, to homoserine
      overproduction. In terms of the regulation of the pathway, the data indicate that
      the main control is exerted by inhibition of the aspartate kinase and that,
      probably, a second and less important regulation takes place at the level of the
      homoserine kinase, the THR1 gene product. However, amplification of THR1 in two
      related Hom3-R2 strains does not increase the amount of threonine but, in one of
      them, it does induce accumulation of more homoserine. This result probably
      reflects differences between these strains in some undetermined genetic factor/s
      related with threonine metabolism. In general, the data indicate that the common
      laboratory yeast strains are genetically rather heterogeneous and, thus,
      extrapolation of conclusions must be done carefully. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18626863
TI  - Modification of native collagen reduces antigenicity but preserves cell
      compatibility.
AB  - Porcine intestinal collagen (ICL), derived from processed small intestine, is
      used as a part of a remodelable bilaminate biosynthetic vascular prosthesis. The
      process for the production of ICL involves mechanical cleaning of non-crosslinked
      porcine intestine (NC-ICL), disinfection with peracetic acid (PA-ICL), and
      crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride
      (PA/EDC-ICL). Two model systems were investigated to evaluate the effect of these
      agents on the humoral response to NC-ICL. First, the antibody titers of rabbits
      immunized with NC-ICL, PA-ICL, and PA/EDC-ICL were determined, and second, the
      humoral response of canines receiving collagenous vascular implants was examined.
      Collagenous and noncollagenous fractions were extracted from NC-ICL, PA-ICL, and
      PA/EDC-ICL and separated by SDS-PAGE. PA and EDC treatment decreased the number
      of extractable proteins as compared to NC-ICL. Immunoblot techniques demonstrated
      anti-NC-ICL antibodies recognized multiple immunoreactive proteins in NC-ICL, but
      not in PA-ICL or PA/EDC-ICL; and rabbits immunized with NC-ICL produced higher
      antibody titers to ICL proteins than rabbits immunized with either PA-ICL or
      PA/EDC-ICL. It was, therefore, apparent that NC-ICL was more antigenic than
      either PA-ICL or PA/EDC-ICL. The humoral immune response of canines to PA/EDC-ICL
      fabricated vascular grafts was determined. At 4 weeks, 8 weeks, and 12 weeks
      postimplant, serum antibodies to ICL proteins or type I collagen could not be
      detected. These data demonstrate a reduced humoral immune response to PA/EDC-ICL.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18626864
TI  - A structured model of dual-limitation kinetics.
AB  - A structured model of substrate-utilization kinetics that encompasses dual
      limitation conditions, caused by simultaneously low concentrations of the
      electron donor and the electron acceptor, is developed by incorporating the
      internal cofactor responses into the kinetic variables. The structured model is
      based on an assumption that the maximum specific electron-donor-oxidation rate
      (q(md)) is not a constant, but is linearly controlled by the intracellular
      chemical potentials, log(NAD/NADH) and log(ATP/ADP . P(i)). Determination of the
      kinetic parameters for the dual-limitation model, using experimental data from
      the companion article, verifies that q(md) varies and demonstrates that the
      NAD/NADH ratio affects q(md) in a positive direction; thus, an increase of the
      ratio increases the rate of electron-donor utilization. Because the internal
      NAD/NADH ratio rises with an increase in S(ar) the specific electron-donor
      utilization rate is accelerated by high S(a). Since the ratio also increases as
      the specific electron-donor-utilization rate falls, the specific rate is
      intrinsically accelerated by the cofactor response when it becomes low due to a
      depletion of electron donor. Because the cofactor responses upon changes of the
      external substrate concentrations are systematic, the dual-limitation model can
      be expressed as a function of only external concentrations of electron donor and
      electron acceptor, which results in a multiplicative (double-Monod) form. Thus,
      dual limitation by both substrates reduces the overall reaction rate below the
      rate expected from single limitation by only one, the most severely limiting,
      substrate. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626865
TI  - Responses of intracellular cofactors to single and dual substrate limitations.
AB  - The highly systematic responses of cellular cofactors to controlled substrate
      limitations of electron donor, electron acceptor, and both (dual limitation) were
      quantified using continuous-flow cultures of Pseudomonas putida. The results
      showed that the NADH concentration in the cells decreased gradually as the
      specific rate of electron-donor utilization (-q(d)) fell or increased
      systematically as oxygen limitation became more severe for fixed -q(d), while the
      NAD concentration was invariant. The NAD(H) responses demonstrated a common
      strategy; compensation for a low concentration of an externally supplied
      substrate by increasing (or decreasing) the concentration of its internal
      cosubstrate (or coproduct). The compensation was dramatic, as the NAD/NADH ratio
      showed a 24-fold modulation in response to depletion of dissolved oxygen (DO) or
      acetate. In the dual-limitation region, the compensating effects toward depletion
      of one substrate were damped, because the other substrate was simultaneously at
      low concentration. However, the NAD(H) responses minimized the adverse impact
      from substrate depletion on overall cell metabolism. Cellular contents of ATP,
      ADP, and P(i) were mostly affected by -q(d), such that the phosphorylation
      potential, ATP/ADP . P(i), increased as -q(d) fell due to depletion of acetate,
      DO, or both. Since the respiration rate should be slowed by high ATP/ADP . P(i),
      the cellular response seems to amplify an unfavorable environmental condition
      when oxygen is depleted. The likely reason for this apparent disadvantageous
      response is that the response of phosphorylation potential is more keenly
      associated with other aspects of metabolic control, such as for synthesis, which
      requires P(i) for production of phospholipids and nucleotides. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18626866
TI  - Editorial.

PMID- 18626867
TI  - The role of hydration in enzyme activity and stability: 1. Water adsorption by
      alcohol dehydrogenase in a continuous gas phase reactor.
AB  - The adsorption of water by alcohol dehydrogenase from baker's yeast (YADH) has
      been measured in a continuous-flow gas reactor at varying temperatures.
      Adsorption isotherms in the presence of gaseous organic substrates are compared
      to those from organic-free gas mixtures. Almost no effect of the hydrophobic
      molecule on total water adsorption was observed. A rarely mentioned multilayer
      isotherm model from the 1930s, the Huttig's isotherm, has been found to fit the
      experimental data with extremely good accuracy. The model enables the calculation
      of both the heat of adsorption of water to the enzyme and the total amount of
      water necessary for monolayer coverage. The heat of adsorption of water in the
      first layer is approximately -16 kcal/mol. This tight binding of water, which is
      much higher than the heat of condensation of pure water, helps to explain the
      kinetic properties of YADH-catalyzed reactions on vapor phase substrates. While
      the monolayer coverage is temperature independent, the enzyme demonstrates
      hysteresis when transitioning between adsorption and desorption. The hysteresis
      observed in water sorption studies may also explain previously reported
      properties of the enzyme. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626868
TI  - The role of hydration in enzyme activity and stability: 2. Alcohol dehydrogenase
      activity and stability in a continuous gas phase reactor.
AB  - The degree of enzyme hydration is the one of the most important factors which can
      affect enzyme activity and stability in water-limited environments. Alcohol
      dehydrogenase from baker's yeast (YADH) has been used as a model enzyme to study
      the effects of hydration on activity, stability, and cofactor stability with gas
      phase substrates. In all cases, the enzyme is essentially inactive until a
      temperature-independent degree of surface coverage by water molecules has been
      reached. The critical water content corresponds to 40-50% of a single monolayer.
      Careful control of the degree of hydration, by adjustments to gas humidity and
      temperature, enables the enzyme to be stabilized for periods exceeding 1 month,
      whereas in water the half-life of the enzyme is 30 min. The reaction with gas
      phase substrates follows a pseudo-first-order mechanism with an activation energy
      of 7.5 +/- kcal/mol, which is almost half of that in aqueous solution. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18626869
TI  - Improved prenatal aneuploidy screening using the novel advanced first-trimester
      screening algorithm: a multicenter study of 10,017 pregnancies.
AB  - PURPOSE: : It has been postulated that the maternal age component should be
      completely excluded from first-trimester screening (FTS) for fetal aneuploidies.
      In this study, we tested a new algorithm known as advanced first-trimester
      screening (AFS), which disregards maternal age. METHOD: : In a multicenter study,
      FTS findings were retrieved from 10,017 pregnancies. FTS risk assessment was
      performed using the Nicolaides method, and the AFS score was calculated. The
      results of both methods were compared. RESULTS: : Within this population, 81
      fetuses had an abnormal karyotype. The sensitivity of the 2 algorithms was 86.4%.
      When the AFS method was used, the positive predictive value rose from 9.6% (FTS)
      to 12.4% (AFS). Using AFS, the test positive rate could be decreased by 161 cases
      (-22.2%) (p < 0.0001), due to a reduction of false positive cases. As a result,
      the false positive rate of AFS was 24.5% lower than that of FTS, while the same
      number of aneuploidies was detected. CONCLUSION: : AFS can markedly reduce the
      rate of false positive test results. If these results are confirmed by larger
      multicenter studies, the new AFS will represent a great improvement in fetal
      aneuploidy screening. (c) 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008.

PMID- 18626870
TI  - Paratracheal lymph nodes: a new sonographic finding in autoimmune thyroiditis.
AB  - PURPOSE: To assess the clinical value of paratracheal lymph nodes (PLNs) as a
      novel sonographic finding in autoimmune thyroiditis (AT). METHODS: A total of 309
      consecutive patients underwent sonographic examinations of the thyroid between
      1998 and 2003. A single radiologist assessed the sonographic findings of AT and
      PLNs. All patients underwent serological tests for antimicrosomal antibodies
      (AMAs). Patients with clinical, cytological, or laboratory findings of
      thyroiditis formed the AT group with a positive AMA test (n = 199). Controls were
      patients with no signs of nodular thyroid disease, normal thyrotropin, negative
      AMA, and benign cytology (n = 110). RESULTS: PLNs were seen in 184 of 199
      patients in the AT group and in 28 of 110 controls (P < 0.001) (sensitivity of
      93.4%, specificity of 74.5% in the diagnosis of AT). PLNs in controls were fewer
      (2.8 +/- 1.5 versus 4.7 +/- 2.6; P < 0.001) and smaller (8.2 +/- 2.4 mm versus
      10.7 +/- 3.3 mm; P < 0.001) than in the AT group. CONCLUSION: PLNs are often
      present in patients with AT and are detectable with sonography. Radiologists
      should be aware of the importance of including the paratracheal region in the
      evaluation of the thyroid gland.

PMID- 18626871
TI  - Combined local and systemic methotrexate treatment of viable ectopic pregnancy:
      outcomes of 31 cases.
AB  - PURPOSE: Medical treatment of viable unruptured ectopic pregnancies by systemic
      methotrexate (MTX) is controversial due to elevated failure rates. This study
      describes a combined local and systemic MTX administration and compares the
      outcomes between viable ectopics in different locations. METHODS: This
      retrospective study evaluated 31 patients treated with combined local
      (sonographically guided) and systemic MTX for viable, unruptured ectopic
      pregnancies. Success was defined by pregnancy resolution without surgical
      intervention. Details on subsequent pregnancies were obtained via telephone
      questionnaires. RESULTS: The ectopic pregnancies were located in the fallopian
      tube (n = 23), cesarean section scar (n = 5), and intramural portion of the tube
      (interstitial pregnancy) (n = 3). beta-Human chorionic gonadotropin levels and
      gestational weeks were similar. The combined treatment was successful in 73.9%,
      100%, and 66.7% of cases, respectively (p > 0.05). Details regarding reproductive
      outcomes were available for 28 women (90.3%). Eighteen of the 24 women attempting
      to conceive became pregnant, and 15 of these had at least one live birth. There
      were three subsequent tubal pregnancies, all in patients with previous tubal
      pregnancies. CONCLUSION: Combined MTX administration is effective and safe for
      treating viable cesarean scar pregnancies but is less successful for viable tubal
      or interstitial pregnancies. Reproductive outcomes following the combined MTX
      treatment are comparable to other treatment modalities for ectopic pregnancy.

PMID- 18626872
TI  - Extracranial and intracranial vertebral artery dissection: long-term clinical and
      duplex sonographic follow-up.
AB  - PURPOSE: To determine the value of color Doppler sonography (CDUS) in the
      diagnosis and follow-up of patients with extracranial and intracranial vertebral
      artery (VA) dissection. METHOD: Thirty-three patients aged 42 +/- 12 years with
      40 VADS confirmed via digital subtraction angiography (DSA) (n = 37) and magnetic
      resonance angiography (MRA) (n = 3) were included in the study. All patients were
      investigated with extracranial CDUS and transcranial CDUS (TCCDUS) over a mean +/
      SD follow-up period of 42 +/- 24 months and occurrence of new ischemic symptoms
      was assessed. Sonographic results were compared with initial and follow-up
      angiographic results. RESULTS: At presentation, 24/33 (73%) patients had suffered
      an ischemic stroke, 5/33 (15%) had a transient ischemic attack (TIA), and 4/33
      (12%) were asymptomatic. Two patients had a recurrent vertebrobasilar TIA; there
      was no recurrent stroke. The initial DSA findings consisted of 14 stenoses, 20
      tapered occlusions, and 6 pseudoaneurysms. During follow-up, 63% of the vessels
      recanalized. Sonographic findings were consistent with angiographic findings in
      80% at the initial examination and in 86% during follow-up. The main reason for
      discordant results was the failure of CDUS to detect pseudoaneurysms. No
      recurrence occurred in the vertebral arteries (VA), but 1 patient had an
      asymptomatic carotid artery dissection during follow-up. CONCLUSION: Recurrent
      TIA or stroke after VAD appears to be extremely rare, independent of
      recanalization or persistent occlusion of the affected artery. CDUS and TCCDUS
      provide reliable follow-up of VAD in all patients presenting with stenosis or
      occlusion, but do not allow for detection of pseudoaneurysms of the VA.

PMID- 18626873
TI  - Construction of a pH-responsive artificial membrane fusion system by using
      designed coiled-coil polypeptides.
AB  - In many viruses, pH-responsive coiled-coil domains in the specific fusion
      proteins play important roles in membrane fusion and the infection of viruses
      into host cells. To investigate the relationship between the conformational
      change of the coiled coil and the fusion process, we have introduced a de novo
      designed polypeptide as a model system of the coiled-coil domain. This system
      enables the systematic study of the dynamics of pH-responsive coiled-coil
      polypeptide-membrane interactions. First, we designed and synthesized pH
      responsive isoleucine-zipper triple-stranded coiled-coil polypeptides. Then the
      relationship between the pH-induced conformational change of the polypeptide and
      the membrane's interactive properties was studied by physicochemical methods.
      Structural changes in the designed polypeptides were examined by means of
      circular dichroism measurements. And finally, the behavior of the membrane fusion
      was investigated by leakage of liposomal contents, turbidity analysis, dynamic
      light scattering, and lipid mixing experiments. Our data show that coiled-coil
      formation under acidic pH conditions enhances polypeptide-induced membrane
      fusion. The results in this study demonstrate that an artificial membrane fusion
      system can be constructed on a molecular level by the use of a pH-responsive
      isoleucine-zipper triple-stranded coiled-coil polypeptide.

PMID- 18626874
TI  - Diversity-oriented synthesis of enantiomerically pure steroidal tetracycles
      employing Stille/Diels-Alder reaction sequences.
AB  - Various steroid analogues were synthesized by Stille coupling of
      bicyclo[4.3.0]nonenylstannanes cis-/trans-8 and 14 with cyclohexenol triflates 17
      and 18 and subsequent Diels-Alder reactions of the resulting dienes. The
      enantiomerically pure bicyclo[4.3.0]nonenylstannanes cis- and trans-8 were
      prepared in good yields via the enol triflates cis- and trans-7, obtained from
      the bicyclo[4.3.0]non-2-en-3-one 5. The alkenylstannane 14 was obtained from the
      [2+2] cycloadduct 10 a produced from addition of dichloroketene to the
      enantiomerically pure and protected bishydroxycyclohexadiene 9 a (65 %).
      Treatment of 10 a with diazomethane, reduction of the dichloromethylene group,
      and trapping with tributyltin chloride after lithium-for-bromine exchange,
      yielded the bicyclo[4.3.0]nonenylstannane 14 (23 % over four steps). Stille
      couplings provided the tricyclic dienes cis-/trans-19 in good yields (73-77 %),
      whereas the tricyclic diene 20 was obtained in only 34 % yield at best. Diels
      Alder reactions of trans-19 with various reactive dienophiles yielded the novel
      steroidal compounds trans-21 to trans-26 with complete diastereoselectivity.
      Heating the dienes cis-19 or 20 with maleic acid derivatives provided the
      corresponding tetracycles cis-23alpha,beta and 27alpha,beta with a cis-C,D ring
      junction, each as mixtures of two diastereomers. Less reactive dienophiles
      required higher temperatures to promote the relevant cycloaddition with trans-19
      to furnish several stereoisomeric forms of trans-28 and trans-29 in significantly
      lower yields (31-45 %). The selected steroid analogues trans-22 and trans-23 were
      deprotected in two steps by using acid catalysis to provide trans-31 and trans-33
      (91 and 80 % over two steps). Cyclopropanation of trans-30 yielded the
      cyclopropasteroid analogue 34 (74 %), treatment of which with trifluoroacetic
      acid furnished the cyclopropasteroid 35 and the 2-methyl-substituted steroid
      analogue 36 in 40 and 12 % yield, respectively. Aromatic B-ring steroids 38 (69
      %) and 39 (5 %) were accessed by dehydrogenation of trans-24 with 2,3-dichloro
      5,6-dicyano-1,4-benzoquinone.

PMID- 18626875
TI  - Dye-modified nanochannel materials for photoelectronic and optical devices.
AB  - Artificial photonic antenna systems have been realised by incorporating organic
      dyes into zeolite L. The size and aspect ratio of the cylindrically shaped
      zeolite crystals can be tuned over a wide range, adding to the versatility of
      this host material. A 600 nm sized crystal, for example, consists of about 96 000
      one-dimensional channels oriented parallel to the cylinder axis. Geometrical
      constraints imposed by the host structure lead to supramolecular organisation of
      the guests, allowing high concentrations of non- or only very weakly interacting
      dye molecules. A special twist is added to these systems by plugging the channel
      openings with a second type of fluorescent dye, a so-called stopcock molecule.
      The two types of molecules are precisely tuned to each other; the stopcocks are
      able to accept excitation energy from the dyes in the channels, but cannot pass
      it back. The supramolecular organisation of dyes in the zeolite channels
      corresponds to a first stage of organisation, allowing light-harvesting within
      the volume of a cylindrical crystal and radiationless energy transport to either
      the cylinder ends or centre. The second stage of organisation represents the
      coupling to an external acceptor or donor stopcock fluorophore at the channel
      entrances, which can then trap or inject electronic excitation energy. The third
      stage of organisation is realised by interfacing the material to an external
      device through a stopcock intermediate. We observed that electronic-excitation
      energy transfer in dye-zeolite L materials occurs mainly along the channel axis
      and we have shown that macroscopically organised materials can be prepared. The
      new materials offer unique possibilities as building blocks for optical, electro
      optical and sensing devices.

PMID- 18626876
TI  - 1,2-Disilacyclobut-2-enes: donor-free four-membered cyclic silenes from reaction
      of disilenides with vinylbromides.

PMID- 18626877
TI  - Gold supported on nanocrystalline beta-Ga2O3 as a versatile bifunctional catalyst
      for facile oxidative transformation of alcohols, aldehydes, and acetals into
      esters.

PMID- 18626879
TI  - Origin, development, and future of spintronics (Nobel Lecture).

PMID- 18626878
TI  - Bismetallocenes: lanthanoid-transition-metal bonds through alkane elimination.

PMID- 18626880
TI  - Poly(biradicals): oligomers of 1,3-diphosphacyclobutane-2,4-diyl units.

PMID- 18626881
TI  - Native chemical ligation at valine.

PMID- 18626882
TI  - Palladium-catalyzed enantioselective oxidation of chiral secondary alcohols:
      access to both enantiomeric series.

PMID- 18626883
TI  - Structure-antioxidant activity relationships in a series of NO-donor phenols.
AB  - Recently we reported a new class of NO-donor phenols that could be of interest in
      the treatment of many forms of cardiovascular disease (CD). Their potencies as
      inhibitors of ferrous salt/ascorbate-induced peroxidation of membrane lipids of
      rat hepatocytes were assessed as pIC(50) values through the TBARS assay. In this
      work we aimed to find quantitative relationships between the antioxidant activity
      of these compounds and appropriate molecular descriptors. In particular, we
      determined their log P(oct), their reactivity (log Z) in reaction with the 2,2
      diphenyl-1-picrylhydrazyl radical (DPPH(.)), and the theoretical parameter
      DeltaH(abs), which describes the enthalpy of homolytic O--H bond cleavage. The
      QSAR equations found through the classical Hansch approach allowed us to draw
      interesting conclusions on the possible mechanisms of reaction with radicals in
      the various environments, while underlining the role of lipophilicity in
      antioxidant activity.

PMID- 18626884
TI  - Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus
      associated T/natural killer-cell lymphoproliferative disease in Japan.
AB  - Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD)
      has been linked to several different disorders. Its prognosis is generally poor
      and a treatment strategy has yet to be established. There are reports, however,
      that hematopoietic stem cell transplantation (HSCT) can cure this disease. To
      clarify the current situation regarding allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was
      performed in Japan. Data for 74 patients were collected. There were 42 cases of
      chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic
      lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia
      (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell
      type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most
      patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year
      after onset compared to only 14% of patients with CAEBV. The event-free survival
      (EFS) rate following allo-HSCT was 0.561 +/- 0.086 for CAEBV, 0.614 +/- 0.186 for
      EBV-HLH, and 0.309 +/- 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with
      conventional conditioning was 0.488 +/- 0.074 and with reduced-intensity
      conditioning was 0.563 +/- 0.124. Thus, in a substantial number of cases, EBV
      associated T/NK-LPD can be cured by either allogeneic conventional stem cell
      transplantation or reduced-intensity stem cell transplantation.

PMID- 18626885
TI  - Treosulfan/fludarabine as an allogeneic hematopoietic stem cell transplant
      conditioning regimen for high-risk patients.
AB  - In recent years, new conditioning regimens have been explored in patients not
      eligible for conventional transplant with the aim to reduce transplant-related
      mortality. In a phase II multicentric prospective trial, we investigated the
      safety and feasibility of the treosulfan-fludarabine combination prior to
      allogeneic hematopoietic stem cell transplant in patients with various
      hematological malignancies not eligible for conventional regimens because of
      previous intensive treatment, older age, and comorbidities. Forty-six consecutive
      patients, median age 48 years (range 17-69), were enrolled. Sixteen of them were
      in complete remission, and 20 had a HSCT comorbidity index > or = 1. Forty-four
      patients had regular and sustained engraftment, and 39 out of 40 evaluable
      patients developed complete chimerism. Nonhematological toxicity was limited.
      Risk of transplant-related mortality was 9% (95% CI, 2-17%) at day +100 and
      plotted at 15% (95% CI, 7-22%) after 7 months. The estimated overall survival and
      progression-free survival with a median follow-up of 20 months were 51% and 38%,
      respectively. The estimated 30 months progression-free survival for patients
      transplanted in remission was 56%. The treosulfan-fludarabine combination is a
      reduced-toxicity but myeloablative regimen that can be proposed to patients not
      fitting criteria for conventional transplant regimens. Longer follow-up and
      further prospective studies are necessary to evaluate this regimen.

PMID- 18626886
TI  - Erythropoiesis-stimulating agents are associated with reduced survival in
      patients with multiple myeloma.
AB  - The impact of erythropoiesis-stimulating agent (ESA) on cancer patients' survival
      has recently become a matter of extensive discussion. Studies in solid tumors
      demonstrated that ESA adversely affects survival. This issue has not been
      sufficiently studied in patients with multiple myeloma. In this study, which
      included 323 multiple myeloma patients followed in our Institution between 1988
      and 2007, we demonstrated by using a proportional hazards model including
      multiple covariates (age, LDH, Hb, platelets, serum creatinine, ISS score, beta2
      microglobulin, and ESA administration) that ESA administration is associated with
      reduced survival (hazards ratio: 1.88, 95% CI: 1.28-2.77). Anemia, which is
      considered a predictor for survival, platelets, serum creatinine, ISS score, and
      LDH, were not significant, whereas, age and beta2 microglobulin confirmed their
      predicting value in the multivariate analysis. With a median follow-up of 31
      months (range 1-238), the median survival of patients in the ESA group was 31
      months (95% CI: 25-37), whereas in the group without ESA administration it was 67
      months (95% CI: 55-79) (P < 0.001). The median progression-free survival for
      patients in the ESA group was 14 months (95% CI: 12-16), and for the group
      without ESA it was 30 months (95% CI: 24-36) (P < 0.001). These results indicate
      that ESA may have a detrimental impact on MM patients' outcomes and, thus, in
      this context, they should be used with rigorous criteria.

PMID- 18626887
TI  - Medication-induced mitochondrial damage and disease.
AB  - Since the first mitochondrial dysfunction was described in the 1960s, the
      medicine has advanced in its understanding the role mitochondria play in health
      and disease. Damage to mitochondria is now understood to play a role in the
      pathogenesis of a wide range of seemingly unrelated disorders such as
      schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine
      headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient
      ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue
      syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary
      biliary cirrhosis. Medications have now emerged as a major cause of mitochondrial
      damage, which may explain many adverse effects. All classes of psychotropic drugs
      have been documented to damage mitochondria, as have stain medications,
      analgesics such as acetaminophen, and many others. While targeted nutrient
      therapies using antioxidants or their precursors (e. g., N-acetylcysteine) hold
      promise for improving mitochondrial function, there are large gaps in our
      knowledge. The most rational approach is to understand the mechanisms underlying
      mitochondrial damage for specific medications and attempt to counteract their
      deleterious effects with nutritional therapies. This article reviews our basic
      understanding of how mitochondria function and how medications damage
      mitochondria to create their occasionally fatal adverse effects.

PMID- 18626888
TI  - Secretion of cortisol and aldosterone as a vulnerable target for adrenal
      endocrine disruption - screening of 30 selected chemicals in the human H295R cell
      model.
AB  - The adrenal gland is a vulnerable target for toxic insult. Disruption of adrenal
      steroidogenesis and hormone secretion may cause serious effects on human health.
      A human in vitro model is needed to predict effects, and elucidate mechanisms of
      endocrine disruption and adrenal toxicity. The human adrenocortical cell line
      H295R has been used to screen for effects on sex hormones. Here, we have analyzed
      the effect of 30 potential endocrine disrupting chemicals on the secretion of
      cortisol and aldosterone from the H295R cells, using specific ELISA assays. The
      effect of chemicals was analyzed for basal and forskolin- or angiotensin II
      stimulated hormone secretion. The chemicals were tested at the highest
      concentration where they displayed no evident unspecific cytotoxicity.
      Quantitative and qualitative differences in effects on hormone secretion were
      demonstrated for the various chemicals. A subset of the chemicals displayed
      different effects on cortisol and aldosterone secretion, and in some cases the
      effects were different between basal and stimulated hormone secretion.
      Aminoglutethimide, prochloraz, ketoconazole, 6-hydroxyflavone, imazalil and
      etomidate had the most marked inhibitory effects on cortisol (with or without
      forskolin) and ketoconazole, 6-hydroxyflavone, imazalil and etomidate had the
      most marked effects on aldosterone (with or without angiotensin II). The results
      are discussed in terms of known effects, structural similarity and possible
      mechanisms. We have shown that adrenal steroidogenesis is a vulnerable target for
      toxic insult and that the H295R assay is a useful in vitro model for screening
      purposes.

PMID- 18626890
TI  - Application of structure-activity relationships to investigate the molecular
      mechanisms of hepatocyte toxicity and electrophilic reactivity of alpha,beta
      unsaturated aldehydes.
AB  - Covalent binding of reactive electrophiles to cellular targets is a molecular
      interaction that has the potential to initiate severe adverse biological effects.
      Therefore, a measure for electrophilic reactivity with biological nucleophiles
      could serve as an important correlate to toxic effects such as hepatocyte death.
      To determine if electrophile reactivity correlates with rat hepatocyte
      cytotoxicity, the inherently electrophilic alpha,beta-unsaturated aldehydes were
      chosen for investigation. Reactivity was measured with simple assays that used
      glutathione, a soft nucleophile, and butylamine, a harder nucleophile, as models
      for protein thiol and amine nucleophilic sites, respectively. Despite their
      higher reactivity with thiols, a linear relationship was only observed between
      hepatocyte cytotoxicity and amine reactivity. Structure-activity relationships
      were also investigated for hepatocyte toxicity, and results showed toxicity was
      well modelled by log P and electronic parameters E(LUMO) and partial charge of
      the carbonyl carbon (C'(carb)). Hydrophobicity and electronic descriptors were
      only significant in separate distinct models, suggesting that there were
      simultaneously occurring mechanisms that affected toxicity. Log P was linked to
      the ease of oxidation by a microsomal aldehyde dehydrogenase enzyme, while the
      electronic descriptors and amine reactivity were linked to direct alkylation.
      Even with the presence of electrophile characteristics, alpha,beta-unsaturated
      aldehyde hepatocyte toxicity could not be predicted exclusively by electrophilic
      reactivity as oxidative metabolism was also a factor for toxicity.

PMID- 18626891
TI  - Increased levels of urinary nitrite and nitrotyrosine in Yusho victims 40 years
      after accidental poisoning with polychlorinated biphenyls in Nagasaki, Japan.
AB  - Forty years have passed since the accidental poisoning with polychlorinated
      biphenyls (PCB) in Japan in 1968, named Yusho. High concentrations of PCB are
      still detected in the serum of the Yusho victims. PCB produces superoxide (O(2) (
      )) in the metabolic process and we reported high concentrations of serum nitrite,
      a stable metabolite reflecting nitric oxide (NO), in the Yusho victims. NO reacts
      with O(2) (-) and immediately produces peroxynitrite (ONOO(-)). ONOO(-) causes
      nitration of tyrosine residues and produces nitrotyrosine (NT). Therefore, we
      measured urinary concentrations of nitrite and NT in the victims and age-matched
      controls. The mean urinary concentrations of nitrite and NT were significantly
      higher than in the controls. There was a positive correlation between urinary
      nitrite and NT in the Yusho victims. Furthermore, there was a positive
      correlation between the ratio of urinary NT to nitrite and serum PCB
      concentrations in the Yusho victims. It was considered that the emergence of some
      ailments could be presumed to have been caused by high levels of urinary nitrite
      and NT in the Yusho victims.

PMID- 18626893
TI  - On the issue of interfacial activation of lipase in nonaqueous media.
AB  - The question of whether lipases can be activated by adsorption onto an interface
      in organic solvents was addressed using Rhizomucor miehei lipase as a model. In
      aqueous solution, this enzyme was shown to undergo a marked interfacial
      activation. However, lipase (either lyophilized or precipitated from water with
      acetone) suspended in ethanol or 2-(2-ethoxyethoxy)ethanol containing triolein
      exhibited no jump in catalytic activity when the concentration of triolein
      exceeded its solubility in these solvents, thereby resulting in formation of an
      interface. To test whether the lack of interfacial activation was due to the
      insolubility of the enzyme in organic media, lipase was covalently modified with
      poly(ethylene glycol). The modified lipase, although soluble in nonaqueous media,
      was still unable to undergo interfacial activation, regardless of the
      hydrophobicity of the interface. This inability was found to be caused by the
      absence of adsorption of lipase onto interfaces in organic solvents, presumably
      because of the absence of the hydrophobic effect (the driving force of lipase
      adsorption onto hydrophobic interfaces in water) in such media. The uncovered
      lack of interfacial adsorption and activation suggests that the short alpha
      helical "lid" covering the active center of the lipase remains predominantly
      closed in nonaqueous media, thus contributing to diminished enzymatic activity.

PMID- 18626894
TI  - Reduction of porous media permeability from in situ Leuconostoc mesenteroides
      growth and dextran production.
AB  - In situ growth of bacteria in a porous medium can alter the permeability of that
      media. This article reveals that the rate of permeability alteration can be
      controlled by the inoculation strategy, nutrient concentrations, and injection
      rates. Based on experimental observations a phenomenological model has been
      developed to describe the inoculation of the porous medium, the in situ growth of
      bacteria, and the permeability decline of the porous medium. This model consists
      of two phases that describe the bacteria in the porous medium: (1) the nongrowth
      phase in which cell transport and retention are occurring; and (2) the growth
      phase in which the retained cells grow and plug the porous media. Transition from
      the transport phase to the growth phase is governed by the growth lag time of the
      cells within the porous medium. The importance of the inoculum injection strategy
      and the nutrient injection strategy is illustrated by the model.

PMID- 18626895
TI  - Protein refolding at high concentration using size-exclusion chromatography.
AB  - A new method to improve refolding yields and to increase the concentration of
      refolded proteins in a single operation has been developed. The method uses size
      exclusion chromatography matrices to perform buffer exchange, aggregate removal,
      and the folding reaction. The reduced diffusion of proteins in gel-filtration
      media has been shown to suppress the nonspecific interactions of partially folded
      molecules, thus reducing aggregation. Hen egg white lysozyme (HEWL) and bovine
      carbonic anhydrase (CAB) were successfully refolded from initial protein
      concentrations of up to 80 mg/mL using Sephacryl S-100 (HR). The aggregation
      reaction for lysozyme was reduced and was only detected at the highest protein
      concentration used. The average recovery of lysozyme was 63%, with an average
      specific activity of 104%. Carbonic anhydrase experiments also showed that
      aggregation was suppressed and the average protein recovery from the column was
      56%, with a specific activity of 81%. This process enables refolding and the
      purification of active species to be achieved in a single step.

PMID- 18626896
TI  - Spatial microbial distributions of nitrifiers and heterotrophs in mixed
      population biofilms.
AB  - Spatial microbial distributions of nitrifiers and heterotrophs in undefined mixed
      population biofilms were experimentally investigated using a microslicer
      technique and correlated with nitrification efficiency of the biofilm system. The
      general stratification of different bacterial groups in the biofilm was simulated
      using a one-dimensional (1-D) mathematical biofilm accumulation model (BAM) and
      compared with the experimental results. Biofilms were cultured at three C : N
      ratios of feed solutions in a partially submerged rotating biological contactor
      (RBC). It was shown that the biofilms were vertically stratified (from biofilm
      surface to substratum). At C : N = 0, heterotrophs and nitrifiers coexisted in
      the outermost biofilm and heterotrophs dominated in the innermost biofilm. At C :
      N = 1.5, heterotrophs outcompeted nitrifiers for dissolved oxygen and space;
      thus, heterotrophs dominated in the outermost biofilm and nitrifiers were present
      only in the deeper biofilm. Nitrifiers and heterotrophs coexisted in the
      innermost biofilm. An increase in the influent C : N ratio resulted in stronger
      stratification of microbial species, as well as inhibition of nitrification. In
      batch experiments, NH(4)--N utilization rate (R(NH(4)--N)) was almost the same at
      each substrate C : N ratio even though NH(4) oxidizers were predominantly present
      in the deeper biofilm. The biofilm performance could not be sufficiently
      explained by the obtained microbial spatial distribution, suggesting that one
      dimensional description of microbial distribution was not good enough and three
      dimensional measurements of microbial spatial distribution is necessary. Total
      bacterial densities increased by a factor of 3-17 with biofilm depth. The
      metabolically active cell fraction decreased from 35 +/- 13% in the outermost
      biofilm to 15 +/- 4% in the innermost biofilm, presumably due to substrate
      limitation. The model predicted more pronounced stratification of nitrifiers and
      heterotrophs than the observed results. This discrepancy could be attributed to
      the real biofilms that were structurally heterogeneous (e.g., water channels),
      which could not be described by the one-dimensional model. The results of this
      study clearly indicate the limitation of 1-D biofilm models to describe the
      extent of stratification of nitrifiers and heterotrophs and suggest a 3-D model
      is necessary.

PMID- 18626897
TI  - On-line monitoring of respiration in recombinant-baculovirus infected and
      uninfected insect cell bioreactor cultures.
AB  - Respiration rates in Spodoptera frugiperda (Sf-9) cell bioreactor cultures were
      successfully measured on-line using two methods: The O(2) uptake rate (OUR) was
      determined using gas phase pO(2) values imposed by a dissolved oxygen controller
      and the CO(2) evolution rate (CER) was measured using an infrared detector. The
      measurement methods were accurate, reliable, and relatively inexpensive. The CER
      was routinely determined in bioreactor cultures used for the production of
      several recombinant proteins. Simple linear relationships between viable cell
      densities and both OUR and CER in exponentially growing cultures were used to
      predict viable cell density. Respiration measurements were also used to follow
      the progress of baculoviral infections in Sf-9 cultures. Infection led to
      increases in volumetric and per-cell respiration rates. The relationships between
      respiration and several other culture parameters, including viable cell density,
      cell protein, cell volume, glucose consumption, lactate production, viral titer,
      and recombinant beta-galactosidase accumulation, were examined. The extent of the
      increase in CER following infection and the time postinfection at which maximum
      CER was attained were negatively correlated with the multiplicity of infection
      (MOI) at multiplicities below the level required to infect all the cells in a
      culture. Delays in the respiration peak related to the MOI employed were
      correlated with delays in the peak in recombinant protein accumulation. DO levels
      in the range 5-100% did not exert any major effects on viable cell densities,
      CER, or product titer in cultures infected with a baculovirus expressing
      recombinant beta-galactosidase.

PMID- 18626898
TI  - High pressure, thermal, and combined pressure-temperature stabilities of alpha
      amylases from Bacillus species.
AB  - Three different alpha-amylases from Bacillus subtilis, B. amyloliquefaciens, and
      B. licheniformis, were mutually compared with respect to thermal stability,
      pressure stability, and combined pressure-temperature stability. Measurements of
      residual enzyme activity and residual denaturation enthalpy showed that the alpha
      amylase from B. licheniformis has by far the highest thermostability and that the
      two other alpha-amylases have thermostabilities of the same order of magnitude.
      FTIR spectroscopy showed that changes in the conformation of the alpha-amylases
      from B. amyloliquefaciens, B. subtilis, and B. licheniformis due to pressure
      occurred at about 6.5, 7.5, and 11 kbar, respectively. It seemed that, for the
      enzymes studied, thermal stability was correlated with pressure stability. As to
      the resistance under combined heat and high pressure, the alpha-amylase from B.
      licheniformis was much more stable than the alpha-amylases from B.
      amyloliquefaciens and B. subtilis, the latter two being about equally stable. It
      appears that under high pressure and/or temperature, B. licheniformis alpha
      amylase is the most resistant among the three enzymes studied.

PMID- 18626899
TI  - Treatment of trichloroethylene (TCE) in a membrane biofilter.
AB  - This article reports on the biodegradation of trichloroethylene (TCE) in a hollow
      fiber membrane biofilter. Air contaminated with TCE was passed through
      microporous hollow fibers while an oxygen-free nutrient solution was recirculated
      through the shell side of the membrane module. The biomass was attached to the
      outside surface of the microporous hollow fibers by initially supplying toluene
      in the gas phase that flows through the fibers. While studies on TCE
      biodegradation were conducted, there was no toluene present in the gas phase. At
      20-ppmv inlet concentration of TCE and 36-s gas-phase residence time, based on
      total internal volume of the hollow fibers, 30% removal efficiency of TCE was
      attained. At higher air flow rates or lower gas-phase residence times, lower
      removal efficiencies were observed. During TCE degradation, the pH of the liquid
      phase on the shell side of the membrane module decreased due to release of
      chloride ions. A mathematical model was developed to describe the synchronous
      aerobic/anaerobic biodegradation of TCE.

PMID- 18626900
TI  - An advanced image analysis system for evaluation of somatic embryo development.
AB  - Somatic embryogenesis is among the most promising means of large scale plant
      micropropagation. The development of somatic embryos is characterized by their
      morphological changes. Embryos in culture usually exhibit high heterogeneity and
      abnormality. As conventional microscopic observation is laborious and subjective,
      an objective and quantitative morphokinetic description is important for further
      advancement of this important process technology. We developed an image analysis
      system capable of measuring morphological and size features of embryos. Subtle
      environmental effects on embryo development, which are often masked by the
      subjectivity of microscopic observation, are now discernible by statistically
      comparing the distributions of these morphological and size features. This image
      analysis and pattern recognition system was applied to examine the kinetics of a
      fed-batch culture.

PMID- 18626901
TI  - A modeling framework for the study of protein glycosylation.
AB  - The key step in the asparagine-linked glycosylation of secretory proteins is the
      transfer of oligosaccharide from a dolichol precursor to the polypeptide at an
      Asp-X-Ser/Thr (NXS/T) consensus sequence. It is often the case, both in cultured
      cells and in vivo, that this reaction does not occur for every molecule of a
      given protein. Thus, the cell may create two protein populations, one bearing and
      one lacking oligosaccharide, for each potential glycosylation site. We present a
      structured kinetic modeling framework of the initial glycosylation event based on
      a balance of available glycosylation sites through the region of endoplasmic
      reticulum lumen proximal to the membrane. Oligosaccharyltransferase, a multimeric
      protein complex, catalyzes the sugar transfer. This enzyme is integral to the
      endoplasmic reticulum membrane, and it is thought to act cotranslationally. The
      nascent polypeptide may also fold in such a way as to prevent glycosylation from
      occurring. The net result is a potentially complex spatial and temporal
      relationship among translation, glycosylation, and other cotranslational events.
      Model results predict how fractional glycosylation site occupancy may depend on
      protein synthesis rate, oligosaccharyldolichol availability, and mRNA elongation
      rate. Although we are currently unable to quantitatively compare predicted to
      experimentally obtained fractional site occupancy, we are able to determine
      qualitative trends which may be confirmed experimentally.

PMID- 18626902
TI  - Prevention of clogging in a biological trickle-bed reactor removing toluene from
      contaminated air.
AB  - Removal of organic compounds like toluene from waste gases with a trickle-bed
      reactor can result in clogging of the reactor due to the formation of an
      excessive amount of biomass. We therefore limited the amount of nutrients
      available for growth, to prevent clogging of the reactor. As a consequence of
      this nutrient limitation a lower removal rate was observed. However, when a
      fungal culture was used to inoculate the reactor, the toluene removal rate under
      nutrient limiting conditions was higher. Over a period of 375 days, an average
      removal rate of 27 g C/(m(3) h) was obtained with the reactor inoculated with the
      fungal culture. From the carbon balance over the reactor and the nitrogen
      availability it was concluded that, under these nutrient-limited conditions,
      large amounts of carbohydrates are probably formed. We also studied the
      application of a NaOH wash to remove excess biomass, as a method to prevent
      clogging. Under these conditions an average toluene removal rate of 35 g C/(m(3)
      h) was obtained. After about 50 days there was no net increase in the biomass
      content of the reactor. The amount of biomass which was formed in the reactor
      equaled the amount removed by the NaOH wash.

PMID- 18626903
TI  - Application of light-emitting diodes in bioreactors: flashing light effects and
      energy economy in algal culture (Chlorella pyrenoidosa).
AB  - Light-emitting diodes (LEDs) were used as the sole light source in continuous
      culture of the green alga Chlorella pyrenoidosa. The LEDs applied show a peak
      emission at 659 nm with a half-power bandwidth of 30 nm. Selection of this
      wavelength range, which is optimal for excitation of chlorophylls a and b in
      their "red" absorption bands makes all photons emitted potentially suitable for
      photosynthesis. No need for additional supply of blue light was found. A
      standardized panel with 2 LEDs cm(-2) fully covered one side of the culture
      vessel. At standard voltage in continuous operation the light output of the diode
      panel appeared more than sufficient to reach maximal growth. Flash operation (5
      mus pulse duration) enables potential use of higher operating voltages which may
      render up to three times more light output. Flat airlift fermentor-type
      continuous culture devices were used to estimate steady state growth rates of
      Chlorella pyrenoidosa as a function of the light flux (micromol photons x m(-2) x
      s(-1)) and the flashing frequency of the light-emitting diodes (which determines
      the duration of the dark "off" time between the 5-micros "on" pulses). At the
      fixed voltage and turbidostat setting applied a 20-kHz frequency, which equals
      dark periods of 45 mus, still permitted the maximum growth rate to become nearly
      reached. Lower frequencies fell short of sustaining the maximal growth rate.
      However, the light flux decrease resulting from lowering of the flash frequency
      appeared to reduce the observed growth rates less than in the case of a similar
      flux decrease with light originating from LEDs in continuous operation. Flash
      application also showed reduction of the quantum requirement for oxygen evolution
      at defined frequencies. The frequency domain of interest was between 2 and 14
      kHz. LEDs may open interesting new perspectives for studies on optimization of
      mixing in mass algal culture via the possibility of separation of interests in
      the role of modulation on light energy conversion and saturation of nutrient
      supply. Use of flashing LEDs in indoor algal culture yielded a major gain in
      energy economy in comparison to luminescent light sources. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18626904
TI  - High-level expression of lacZ under control of the tac or trp promoter using
      runaway replication vectors in Escherichia coli.
AB  - To determine the utility of coupling runaway replication to the expression of
      cloned genes under the control of strong promoters, lacZ transcriptional fusions
      to the trp or tac promoter (Ptrp or Ptac) were constructed using plasmids in
      which the copy number is thermally regulated. Cells containing these plasmids
      were able to produce beta-galactosidase to levels between 3700 and 46,000 Miller
      units when induced only by a temperature upshift. The addition of the appropriate
      chemical inducer, either IPTG (isopropyl-beta-D-thiogalactopyranoside) or IAA (3
      beta-indoleacrylic acid), did not significantly enhance the thermal induction.
      The Ptac-controlled and Ptrp-controlled lacZ induction differed slightly in that
      the Ptac-controlled thermal induction exhibited a lag of approximately 1.5 h as
      compared to both chemical and thermal induction, whereas in the case of Ptrp
      controlled induction, an increase in beta-galactosidase expression above
      background occurred at approximately the same time regardless of the means of
      induction. The best vector, a Ptrp-controlled lacZ fusion carried on a runaway
      replication vector having a basal copy number of 10, was able to mediate the
      expression of beta-galactosidase to approximately 40,000 Miller units of beta
      galactosidase comprising 25% of the total cell protein at 17 h postinduction
      under optimal conditions for protein yield. In these cells, lysis occurred as
      lacZ was maximally expressed. Under noninducing conditions, the plasmids were
      stable for at least 60 generations in the absence of antibiotic in batch culture.

PMID- 18626905
TI  - Methyl palmitate prevents CCl(4)-induced liver fibrosis.
AB  - Liver fibrosis is characterized by an excess of collagen fiber deposition, and it
      is known that Kupffer cells play an important role by immunomodulation of the
      toxic response. Methyl palmitate (MP) is an effective Kupffer cell inhibitor. The
      aim of this work was to evaluate the effect of MP on experimental liver fibrosis.
      Four groups were formed: the control group, which received the vehicles only;
      CCl(4) group (0.4 g kg(-1), i.p., three times a week, for eight weeks); CCl(4)
      plus MP (300 mg kg(-1), i.p., daily); and MP alone. Alanine aminotransferase was
      increased by CCl(4), and MP did not prevent this increase. Lipid peroxidation was
      increased markedly by CCl(4); again, MP was not able to prevent this effect.
      Fibrosis increased nearly 6-fold (measured as liver hydroxyproline content) in
      the CCl(4) group; MP preserved the normal content of collagen. These results were
      corroborated by histopathology. To elucidate the antifibrogenic mechanism of MP,
      we measured the production of TGF-beta; CCl(4) increased this cytokine several
      fold, and MP abolished this increase. Collectively the present results indicate
      that MP possesses a strong antifibrogenic effect at least in the CCl(4) model of
      fibrosis. The antifibrotic effect of MP is probably associated with its ability
      to reduce TGF-beta content, maybe by immunomodulation of Kupffer cells
      functioning.

PMID- 18626906
TI  - National trends in silicosis mortality in the United States, 1981-2004.
AB  - BACKGROUND: This article describes trends in mortality with silicosis and
      identifies industries and occupations with elevated silicosis mortality. METHODS:
      A total of 6,326 deaths with silicosis for 1981-2004 were analyzed for trends and
      association with occupation and industry. Annual mortality rates were age
      adjusted to the U.S. Year 2000 population. A linear regression model was used for
      analyzing mortality trends. Proportionate mortality ratios (PMRs) were based on
      1,440 deaths with information on usual industry and occupation. RESULTS: Overall
      age-adjusted mortality rates per million declined from 2.4 in 1981 to 0.7 in
      2004. Industries having significantly elevated PMRs for silicosis included mining
      and quarrying. Occupations with elevated PMRs included those associated with
      metal and mineral processing. CONCLUSIONS: The results suggest that considerable
      progress has been made towards elimination of this preventable disease. However,
      about 30 silicosis deaths per year have been recorded since 1995 among those of
      working age, warranting continued efforts to effectively limit workplace
      exposures.

PMID- 18626907
TI  - Structural organization of the cytoskeleton in SV40 human corneal epithelial
      cells cultured on nano- and microscale grooves.
AB  - The basement membrane of human corneal epithelial cells (HCECs) has a three
      dimensional nanoscale architecture, which includes pores, bumps and fibers that
      may influence cell-substrate adhesion and spreading in the overlying cells. We
      previously demonstrated that nano- and microscale groove and ridge patterns
      influence the morphological response and the adhesive response of HCECs to a
      nominal wall shear stress. Cell-substrate adhesion is mediated by adhesion
      receptors that bind to extracellular matrix components and anchor the
      cytoskeleton (CSK) of cells to extracellular elements. Here we investigate the
      CSK organization in SV40-transformed HCECs grown on nano- and microscale groove
      and ridge patterns. X-ray lithography was used to fabricate uniform groove and
      ridge patterns with features ranging in size from 200 nm to 2 microm grooves.
      Scanning electron microscopy and transmission electron microscopy were used to
      investigate CSK structure and the distribution of -beta1 integrin adhesion
      receptors. CSK elements aligned with the patterns; however, the spatial
      organization of these elements was influenced by feature size. Larger CSK bundles
      lay on top of the ridges and ran parallel to the patterns, whereas smaller CSK
      bundles, whose width was proportional to the groove size, spanned the grooves. 
      Beta1 integrins co-localized with the CSK and had a higher density at the poles
      of aligned spindle-shaped cells. Differences in organization seen on the
      different topographical feature sizes may be indicative of differences in
      extracellular matrix organization. This may explain, in part, previous
      observations regarding the dependence of cell adhesive responses on the size of
      topographic features in the substrate.

PMID- 18626908
TI  - The effects of fur rubbing on the social behavior of tufted capuchin monkeys.
AB  - Fur rubbing has often been attributed as a social as well as a medicinal function
      in capuchin monkeys, yet to date there have been no studies investigating the
      effects of fur rubbing on subsequent group dynamics. Here, we report for the
      first time how social group cohesion is affected by fur rubbing in tufted
      capuchin monkeys. Fifteen captive capuchins were each observed six times for 45
      min, three times following the provision of materials typically used for fur
      rubbing (onion) and three times following control food items (apple). When
      compared with the apple condition, monkeys significantly increased proximity to
      one another in the first 15 min of the onion condition, which is when most fur
      rubbing took place. Moreover, monkeys were more likely to spend time in groups
      when fur rubbing but less likely to spend time in groups when manipulating the
      onion in other ways. In subsequent periods monkeys were less likely to be in
      proximity to one another in the onion condition compared with the apple
      condition. Aggression between group members was elevated whereas affiliation was
      decreased throughout the onion condition. In short, capuchins spent more time
      further apart and engaged in more aggressive acts and shorter affiliative acts
      following fur-rubbing bouts. It is possible that these differences in behavior
      could be owing to differences in how the monkeys competed for and interacted with
      the items presented in each condition rather than due to fur rubbing as such.
      Alternatively, fur rubbing with pungent materials might interfere with olfactory
      cues used to regulate social interactions within a group and thereby cause
      increased levels of aggression.

PMID- 18626909
TI  - Occupational risk factors for endometrial cancer among textile workers in
      Shanghai, China.
AB  - OBJECTIVE: A case-cohort study was conducted to investigate associations between
      occupational exposures and endometrial cancer nested within a large cohort of
      textile workers in Shanghai, China. METHODS: The study included 176 incident
      endometrial cancer cases diagnosed from 1989 to 1998 and a randomly-selected age
      stratified reference subcohort (n = 3,061). Study subjects' complete work
      histories were linked to a job-exposure matrix developed specifically for the
      textile industry to assess occupational exposures. Hazard ratios (HR) and 95%
      confidence intervals were calculated using Cox proportional hazards modeling
      adapted for the case-cohort design, adjusting for age at menarche and a composite
      variable of gravidity and parity. RESULTS: An increased risk of endometrial
      cancer was detected among women who had worked for > or =10 years in silk
      production (HR = 3.8, 95% CI 1.2-11.8) and had exposure to silk dust (HR = 1.7,
      95% CI 0.9-3.4). Albeit with few exposed women (two cases and eight subcohort
      women), there was a 7.4-fold increased risk associated with > or =10 years of
      silica dust exposure (95% CI 1.4-39.7). CONCLUSIONS: The findings suggest that
      some textile industry exposures might play a role in endometrial carcinoma and
      should be further replicated in other occupational settings.

PMID- 18626910
TI  - Just in the wrong place...?: geographic tools for occupational injury/illness
      surveillance.
AB  - BACKGROUND: Geographic analysis is now integral to public health surveillance,
      but has been underused for occupational injury/illness. METHODS: Mapping and
      spatial statistics are used to examine national county-level mean establishment
      Lost Workday Injury/Illness (LWDII) rates in the Occupational Safety and Health
      Administration (OSHA) Data Initiative (ODI), 1997-2001. The following questions
      are explored: Does occupational injury/illness vary geographically at the county
      level?; Does variation remain after accounting for industry hazard?; Where are
      rates higher or lower than expected? RESULTS: The methods provide evidence of
      geographic variation in nonfatal occupational injury/illness rates, including
      after adjusting for industry hazard. CONCLUSIONS: Geographic analyses can improve
      intervention targeting, suggest risk factors for investigation, and make the case
      for targeting resources to prevention in hard-hit areas, as well as improving
      ongoing surveillance.

PMID- 18626911
TI  - Occupational wood dust exposure and the risk of laryngeal cancer: a population
      based case-control study in Germany.
AB  - BACKGROUND: To investigate the effect of exposure to wood dust on the risk of
      laryngeal cancer. METHODS: A population-based case-control study on laryngeal
      cancer was conducted in South-West Germany between 1st of May 1998 to 31st of
      December 2000 with 257 histologically confirmed cases (236 males, 21 females),
      age 37 to 80 years, and 769 population controls (702 males, 67 females), 1:3
      frequency matched by age and sex. Occupational exposures and other risk factors
      were obtained with face-to-face interviews using a detailed standardized
      questionnaire. The complete individual work history was assessed. Work conditions
      were obtained by job-specific questionnaires for selected jobs known to be
      associated with exposure to potential carcinogens. Additionally, a specific
      substance check-list was used as a method for exposure assessment. RESULTS: 43
      (16.7%) cases (41 males, 2 females) and 107 (13.9%) controls (105 males, 2
      females) reported wood dust exposure. Numbers were almost identical for two
      different methods of exposure assessment; however, the agreement of these methods
      was around 95%. A strong effect on laryngeal cancer risk after adjustment for
      smoking, alcohol and education was observed for high exposure to hardwood dust
      (OR = 2.6, 95% CI 1.3-5.2) and to softwood dust (OR = 2.2, 95% CI 1.1-4.2), as
      assessed by substance list. CONCLUSIONS: Our findings for higher exposure to
      hardwood and softwood dust contribute to the evidence that wood dust, in
      particular from hardwood is an independent risk factor.

PMID- 18626913
TI  - Spin-ladder iron oxide: Sr3Fe2O5.

PMID- 18626914
TI  - Ru-hbpp-based water-oxidation catalysts anchored on conducting solid supports.

PMID- 18626916
TI  - A "compartmental" Borromean weave coordination polymer exhibiting saturated
      hydrogen bonding to anions and water cluster inclusion.

PMID- 18626917
TI  - Discrete and well-defined hydrophobic phases confined in self-assembled spherical
      complexes.

PMID- 18626918
TI  - Ultrastructural investigation of coelomocytes in representatives of Naidinae and
      Rhyacodrilinae (Annelida, Clitellata, Tubificidae).
AB  - Various types of free-floating cells are found in the coelomic fluid of
      representatives of several annelid groups. The ultrastructure of these
      "coelomocytes," however, has been studied to a limited degree. In this study, we
      used a transmission electron microscope to investigate the coelomocytes in
      specimens of five species of Naidinae and three species of Rhyacodrilinae (all
      oligochaetous clitellates within the family Tubificidae). These were compared
      with each other and with previously described coelomocytes of representatives of
      other oligochaete taxa. Only one distinguishable coelomocyte type was found in
      the studied specimens: a round to oblong cell without pseudopodia or other
      appendages, primarily containing membrane-bound granules of varying electron
      density, a prominent network of rough endoplasmic reticulum, and free ribosomes.
      This type differs to a great extent from most of the previously described
      coelomocytes, but shows similarities to certain types found in members of
      Enchytraeidae and Megascolecidae. Although we noticed some variation, we did not
      find any ultrastructural characters in these cells obviously useful for
      phylogenetic studies within Tubificidae.

PMID- 18626919
TI  - The external gills of anuran amphibians: comparative morphology and
      ultrastructure.
AB  - The external gills of anuran amphibians are transient structures, covered by the
      development of the operculum and regressing soon afterwards. Their functional
      role has been regarded as equivocal. However, detailed morphological analysis has
      been limited. Analysis of 21 species from six families using scanning and
      transmission electron microscopy revealed diversity at the anatomical and
      cellular levels in extent and length of gill filaments, numbers of surface
      ciliated cells, width of water-blood barrier distance, and evidence of gill
      motility. The most highly developed external gills were found in species with
      delayed hatching, such as Phyllomedusa trinitatis, or in species in which
      hatchlings hang from the surface film of temporary ponds, such as Phrynohyas
      venulosa in which gills added 26-38% to body surface area. In one family, the
      bufonids, all four species examined had poorly developed gills, but in other
      families where we examined several species, the hylids and leptodactylids, there
      was considerable diversity of external gills, suggesting flexible adaptation to
      incubation and hatching environment.

PMID- 18626920
TI  - High-activity variants of the uMAOA polymorphism increase the risk for depression
      in a large primary care sample.
AB  - Studies on the association between the functional uMAOA polymorphism and
      depression have yielded non-conclusive results up till now. One thousand two
      hundred twenty eight consecutive Spanish primary care attendees, participating in
      the PREDICT study, agreed to take part in this genetic PREDICT-Gene study. We
      explored the association between depression and either high-activity uMAOA
      alleles or genotypes. Depression was diagnosed using the Composite International
      Diagnostic Interview (CIDI) to establish three different depressive outcomes (ICD
      10 Depressive Episode (DE), ICD-10 Severe Depressive Episode (SDE) and DSM-IV
      Major Depression (MD)). uMAOA genetic variation was determined by PCR
      amplification and subsequent electrophoresis. Crude and adjusted (gender and/or
      age) odds ratios, with 95% confidence intervals, were calculated for the
      associations between allele or genotype frequencies and all three depressive
      outcomes. We found associations between all three depressive phenotypes and
      either high-activity alleles or high-activity genotypes in both sexes. The
      associations were statistically significant for females but not for males.
      Testing the same associations on the entire sample (males and females) also
      yielded significant associations between depression and either high-activity
      alleles or high-activity genotype distribution that were independent of age
      and/or gender (ICD-10 DE: OR = 1.98; 95% CI: 1.42-1.77; P = 0.00002; ICD-10-SDE:
      OR = 2.05; 95% CI: 1.38-3.05; P = 0.0002; DSM-IV MD: OR = 1.91; 95% CI: (1.26
      2.91); P = 0.0014). Our results provide fairly consistent evidence that high
      activity variants of the MAOA promoter polymorphism confer a modestly higher risk
      for depression.

PMID- 18626921
TI  - Combined pure red cell aplasia and autoimmune hemolytic anemia in systemic lupus
      erythematosus with anti-erythropoietin autoantibodies.
AB  - A 42-year-old woman with systemic lupus erythematosus was admitted to our
      hospital because of severe anemia. Her bone marrow was almost normocellular and
      erythroblasts were nearly absent. Laboratory data showed elevated levels of
      lactate dehydrogenase and positive findings on Coombs' tests. On the basis of
      these findings, her anemia was diagnosed as the overlap of pure red cell aplasia
      with autoimmune hemolytic anemia. Radioimmunoprecipitation assay revealed that
      her serum was positive for anti-erythropoietin antibodies before therapy.
      Furthermore, the autoantibodies inhibited proliferation of an erythropoietin
      dependent cell line in a dose-dependent manner. Immunosuppressive treatment
      improved the anemia accompanied with disappearance of the autoantibodies.

PMID- 18626922
TI  - Hybridization between Crocodylus acutus and Crocodylus moreletii in the Yucatan
      Peninsula: I. Evidence from mitochondrial DNA and morphology.
AB  - The American crocodile (Crocodylus acutus) and the Morelet's crocodile (C.
      moreletii) are broadly sympatric in Belize and Mexico. The presence of
      morphologically anomalous individuals in the overlapping range area suggests
      possible hybridization between these species. Analysis of 477 base pairs of the
      mitochondrial tRNA(Pro)-tRNA(Phe)-Dloop region revealed the presence of pure C.
      acutus (N=43) and C. moreletii (N=56), as well as a high proportion of
      interspecific hybrids (N=17, 14.6%) in the Yucatan Peninsula, Mexico. Although
      all individuals could be assigned to one species or other based on phenotypic
      characters, some had been characterized as potential hybrids in the field by
      anomalous scale counts. The hybridization zone lies along the area of sympatry
      between C. acutus and C. moreletii investigated in this study, but extends
      further inland if hybrid localities from Belize are included. Hybridization in
      the Yucatan Peninsula is bidirectional, which indicates considerably more genetic
      contact between these species than previously recognized, and is probably more
      detrimental to the genetic integrity of smaller C. acutus populations. A more
      intensive study of the pattern of hybridization is warranted and supports
      continued classification of C. acutus as a critically threatened species in the
      Yucatan Peninsula.

PMID- 18626923
TI  - Winding up great expectations.

PMID- 18626924
TI  - Group analytic therapy for eating disorders: preliminary results in a single
      group study.
AB  - OBJECTIVES: There is a lack of empirical data on the effectiveness and process of
      group-analytic therapy in eating disorders. This single-group study aimed to
      explore the effectiveness of such treatment for anorexic and bulimic individuals.
      METHOD: Eight patients (three anorexic and five bulimic women) entered group
      analytic treatment, meeting weekly for 2 years. Eating behaviours, overall
      psychological distress and group process variables were regularly assessed using
      quantitative and qualitative measures, with comparisons made at the beginning and
      end of the therapy. RESULTS: Treatment was discontinued in two cases. When
      outcome was classified on the basis of reliable change and clinical significance
      for the remaining patients at the end of treatment, four were recovered in terms
      of overall psychological distress, while one was unchanged and one had
      deteriorated. In terms of eating disorder symptoms, three patients were
      recovered, two were unchanged and one had deteriorated. Patients experienced an
      overall positive group climate and a positive group alliance. Perception of being
      understood by the therapist appeared to play an important role in the therapeutic
      process. CONCLUSIONS: These preliminary results suggest that group-analytic
      therapy may be effective in helping patients with eating disorders. However, more
      work is needed before firm conclusions can be drawn. Implications for clinical
      practice and future research are discussed.

PMID- 18626928
TI  - Development of thermophilic methanogenic sludge in compartmentalized upflow
      reactors.
AB  - The characteristics and development of thermophilic anaerobic sludge in upflow
      staged sludge bed (USSB) reactors were studied. The compartmentalized reactors
      were inoculated with partially crushed mesophilic granular sludge and then fed
      with either a mixture of volatile fatty acids (VFA) or a mixture of sucrose and
      VFA. The staged degradation of the soluble substrate in the various compartments
      led to a clear segregation of specific types of biomass along the height of the
      reactor, particularly in reactors fed with the sucrose-VFA mixture. Both the
      biological as well as the physical properties of the cultivated sludge were
      affected by the fraction of nonacidified substrate. The sludge in the first
      compartment of the reactor treating the sucrose-VFA mixture was whitish and
      fluffy, most likely resulting from the development of acidifying bacteria. Sludge
      granules which developed in the top part of this reactor possessed the highest
      acetogenic and methanogenic activity and the highest granule strength as well.
      The experiments also revealed that the conversion of the sucrose-VFA mixture into
      methane gradually deteriorated at prolonged operation at high organic loading
      rates (50 to 100 g COD x L(-1) x day(-1)). Stable long-term performance of a
      reactor can only be achieved by preserving the sludge segregation along the
      height of the reactor. In the reactor fed solely with the VFA mixture little
      formation of granular sludge occurred. In this reactor, large differences in
      sludge characteristics were also observed along the reactor height. Li(+)-tracer
      experiments indicated that the hydraulic regime in the USSB reactor is best
      characterized by a series of at least five completely mixed reactors. The
      formation of granular sludge was found to influence the liquid flow pattern.

PMID- 18626929
TI  - Dynamic ultrafiltration model for proteins: a colloidal interaction approach.
AB  - A rigorous dynamic mathematical model for predicting the rate of ultrafiltration
      of proteins has been developed. The model is based on sophisticated descriptions
      of the protein-protein interactions within the layer close to the membrane
      surface which are responsible for controlling permeation rate. Electrostatic
      interactions are accounted for by a Wigner-Seitz cell approach, including a
      numerical solution of the nonlinear Poisson-Boltzmann equation. London-van der
      Waals forces are calculated using a computationally efficient means of
      approximating screened, retarded Lifshitz-Hamaker constants. Configurational
      entropy effects are calculated using an equation of state giving excellent
      agreement with molecular dynamic data. Electroviscous effects are also taken into
      account. These descriptions of protein-protein interactions are used to develop
      an a priori model, with no adjustable parameters, that allows quantitative
      prediction of the rate of filtration of proteins as a function of zeta potential
      (and hence pH), ionic strength, applied pressure, protein size, and membrane
      resistance. A comparison with experimental data for the filtration of bovine
      serum albumin (BSA) shows that the model is in excellent agreement with such
      data.

PMID- 18626925
TI  - Disparities in defining disparities: statistical conceptual frameworks.
AB  - Motivated by the need to meaningfully implement the Institute of Medicine's
      (IOM's) definition of health care disparity, this paper proposes statistical
      frameworks that lay out explicitly the needed causal assumptions for defining
      disparity measures. Our key emphasis is that a scientifically defensible
      disparity measure must take into account the direction of the causal relationship
      between allowable covariates that are not considered to be contributors to
      disparity and non-allowable covariates that are considered to be contributors to
      disparity, to avoid flawed disparity measures based on implausible populations
      that are not relevant for clinical or policy decisions. However, these causal
      relationships are usually unknown and undetectable from observed data.
      Consequently, we must make strong causal assumptions in order to proceed. Two
      frameworks are proposed in this paper, one is the conditional disparity framework
      under the assumption that allowable covariates impact non-allowable covariates
      but not vice versa. The other is the marginal disparity framework under the
      assumption that non-allowable covariates impact allowable ones but not vice
      versa. We establish theoretical conditions under which the two disparity measures
      are the same and present a theoretical example showing that the difference
      between the two disparity measures can be arbitrarily large. Using data from the
      Collaborative Psychiatric Epidemiology Survey, we also provide an example where
      the conditional disparity is misled by Simpson's paradox, whereas the marginal
      disparity approach handles it correctly.

PMID- 18626930
TI  - Biological sulfate reduction using synthesis gas as energy and carbon source.
AB  - Biological sulfate reduction was studied in laboratory-scale gas-lift reactors.
      Synthesis gas (gas mixtures of H(2)/CO/CO(2)) was used as energy and carbon
      source. The required biomass retention was obtained by aggregation and
      immobilization on pumice particles. Special attention was paid to the effect of
      CO addition on the sulfate conversion rate, aggregation, and aggregate
      composition.Addition of 5% CO negatively affected the overall sulfate conversion
      rate; i.e., it dropped from 12-14 to 6-8 g SO(2-) (4)/L day. However, a further
      increase of CO to 10 and 20% did not further deteriorate the process. With
      external biomass recycling the sulfate conversion rate could be improved to 10 g
      SO(2-) (4)/L day. Therefore biomass retention clearly could be regarded as the
      rate-limiting step. Furthermore, CO affected the aggregate shape and diameter.
      Scanning electron microscopy (SEM) photographs showed that rough aggregates
      pregrown on H(2)/CO(2) changed into smooth aggregates upon addition of CO.
      Addition of CO also changed the aggregate Sauter mean diameter (d(32)) from 1.7
      mm at 5% CO to 2.1 mm at 20% CO. After addition of CO, a layered biomass
      structure developed. Acetobacterium sp. were mainly located at the outside of the
      aggregates, whereas Desulfovibrio sp. were located inside the aggregates.

PMID- 18626931
TI  - Simulation of particle size distribution changes occurring during high-pressure
      disruption of bakers' yeast.
AB  - Measurements of size distributions are provided for the breakage of commercial
      packed bakers' yeast cells as a function of operating pressure and number of
      passes through a Manton Gaulin high-pressure homogenizer. A two parameter model
      was developed, based upon the use of a Boltzmann function, to simulate the
      changes in size distribution that accompany the cell breakage process. The
      effects of operating pressure and number of passes are incorporated in the model
      and the result is used to simulate the particle size distribution of the cell
      homogenate. The results show that there is little breakage below a threshold
      pressure of 115 bar and above which breakage is critically dependent upon the
      pressure and number of passes through the homogenizer. The analysis provides a
      means of studying the efficiency of centrifugation that may follow cell
      disruption and provides the basis for further studies of size distribution
      changes accompanying cell disruption.

PMID- 18626932
TI  - Aggregation of ligand-modified liposomes by specific interactions with proteins.
      I: Biotinylated liposomes and avidin.
AB  - The aggregation of biotin-modified phospholipid vesicles (liposomes) induced by
      binding the protein avidin in solution is analyzed experimentally and
      theoretically. Avidin has four binding sites that can recognize biotin
      specifically, and is able to cross-link the liposomes to form large aggregates.
      The aggregation kinetics were followed using quasi-elastic light scattering (QLS)
      to measure the mean particle size, and by measuring the solution turbidity. The
      rate and extent of aggregation were determined as a function of vesicle
      concentration, protein concentration, and the biotin density on the surface of
      the liposomes. A model based on Smoluchowski kinetics, fractal concepts, and
      Rayleigh and Mie light scattering theory was developed to analyze the
      experimental observations. Small aggregates (<7800 A diameter) may be treated as
      globular; however, the fractal nature of larger particles must be taken into
      account. Parameters in the model are taken from molecular simulations, or fit to
      the experimental observations. The aggregation kinetics are primarily determined
      by the biotin density on the liposome surface, the stoichiometric ratio of avidin
      molecules to liposomes, and the liposome concentration. Good agreement is found
      between the model and the experimental results.

PMID- 18626933
TI  - Aggregation of ligand-modified liposomes by specific interactions with proteins.
      II: Biotinylated liposomes and antibiotin antibody.
AB  - The aggregation of biotinylated phospholipid vesicles (liposomes) cross-linked by
      antibiotin IgG was studied experimentally and theoretically. The liposomes were
      either low density liposomes that contained 0.4 mol% biotinylated phospholipid (
      approximately 100 exposed biotin molecules per liposome), or high density
      liposomes that contained 2.7 mol% biotinylated phospholipid ( approximately 1000
      exposed biotin molecules per liposome). The solution turbidity and mean particle
      size measured by quasi-elastic light scattering (QLS) were monitored throughout
      the aggregation. Three different lots of antibiotin antibodies, each with
      different association constants and binding heterogeneities, were used. The
      antibody binding characteristics affected the aggregation rates. The aggregation
      kinetics were analyzed using a model based on the Smoluchowski theory of
      aggregation, fractal concepts of aggregate microstructure, and Rayleigh and Mie
      light scattering theory. The experimental conditions of liposome concentration,
      protein concentration, and ligand density under which aggregation occurred
      correlated well with calculated sticking probabilities based on isotherms
      describing the adsorption of antibiotin antibody to the liposomes. These results
      are compared with prior observations made when avidin was used as the cross
      linking protein.

PMID- 18626934
TI  - Use of the weighted jackknife method to calculate the variance in cellular
      specific protein secretion rate: application to monoclonal antibody secretion
      rate kinetics in response to osmotic stress.
AB  - The specific secretion rate (q, microg protein secreted/viable cell-h) and its
      variance are very useful to compare the capability of cell lines for protein
      secretion. An assessment of specific secretion rate variability is also
      beneficial and important when the specific secretion rate is to be used as an on
      line process parameter to monitor culture production behavior or for in-process
      decisionmaking. Experimental errors in mammalian cell culture (e.g., protein
      concentration measurement and cell counting) and estimation error in the method
      of calculating q contribute to the total variance of the specific secretion rate.
      Although the variance of q is essential for comparing the differences between
      cell lines and the response of the same cell line to different nutrient or
      environmental conditions, few methods for calculating the variance of the
      specific secretion rate have been reported. As a model system, we have used the
      weighted jackknife method and the delta method to calculate the variance in the
      specific secretion rate of a murine monoclonal antibody (q(mAb)) determined by a
      differential method. These methods were applied to calculate q(mAb) and its
      standard deviation to determine the change in q(mAb) kinetics during batch
      culture of the 9.2.27 hybridoma in response to growth in hyperosmotic media or
      osmotic stress. Without osmotic stress, during exponential growth in DMEM + 5%
      FBS spinner culture, the estimate of q(mAb) decreases at least threefold. Results
      indicate that the 9.2.27 hybridoma responds to hyperosmotic media (400 mOsm, 470
      mOsm) by significantly reducing the degree of q(mAb) decrease in the exponential
      phase, thus maintaining a higher q(mAb) through the stationary phase. The trend
      of q(mAb) during the batch cultures studied is further confirmed by t-test.
      Osmotic stress is statistically shown to be able to alter significantly the
      hybridoma-specific mAb secretion kinetics during batch culture. Determination of
      the variance of specific secretion rate using the weighted jackknife method
      offers a powerful approach for establishing the confidence limits of specific
      protein secretion rate between cell cultures in different nutritional or osmotic
      environments.

PMID- 18626935
TI  - Increased PHB productivity by high-cell-density fed-batch culture of Alcaligenes
      latus, a growth-associated PHB producer.
AB  - Alcaligenes latus, a growth-associated PHB producer, was cultivated by a pH-stat
      modal fed-batch culture technique to attain high PHB productivity. Both sucrose
      solution and inorganic medium were fed in conjunction with the supply of ammonia
      solution which serves as a nitrogen source and as a means of pH control.
      Compositions of the inorganic medium were formulated by elemental analysis of A.
      latus cell mass. The effect on inoculum size was examined to reduce culture time.
      High concentrations of cell (142 g/L) and PHB (68.4 g/L) were obtained in a short
      culture time (18 h) with an inoculum size of 13.7 g/L. The PHB content and the
      PHB productivity at the end of the fed-batch culture were 50% of dry cell weight
      and 4.0 g PHB/(L . h), respectively.

PMID- 18626936
TI  - Protein extraction using the sodium bis(2-ethylhexyl) phosphate (NaDEHP) reverse
      micellar system.
AB  - The reverse micellar system of sodium bis(2-ethylhexyl) phosphate
      (NaDEHP)/isooctane/brine was used for liquid-liquid extraction of proteins. We
      investigated the solubilization of cytochrome-c and alpha-chymotrypsin into the
      NaDEHP reverse micellar phase by varying the pH and NaCl concentration in the
      aqueous phase. At neutral pH and relatively low ionic strength, the proteins are
      extracted into the micellar phase with high yield. By contacting the micellar
      phase with a divalent cation (e.g., Ca(2+)) aqueous solution, the reverse
      micelles are destabilized and release the protein molecules back into an aqueous
      solution for recovery. This method separates the proteins from the surfactant
      with very high overall efficiencies.

PMID- 18626937
TI  - Production and isolation of chitosan by submerged and solid-state fermentation
      from Lentinus edodes.
AB  - A method for the laboratory-scale production and isolation of chitosan
      (polyglucosamine) by liquid and solidstate fermentation from Lentinus edodes was
      developed. The yields of isolated chitosan were 120 mg/L of fermentation medium
      under liquid fermentation conditions and 6.18 g/kg of fermentation medium under
      solid-state fermentation conditions. The latter method, which gives up to 50
      times yields than other chitosan production methods from fungi, provides a new
      flexible and easily scaledup procedure for the production of low acetylation
      degree chitosan.

PMID- 18626938
TI  - Collagenase digestion of bone fragments in microgravity.
AB  - The effect of a quiescent microgravity fluid environment on the activity of
      collagenase directed at demineralized bone fragments was investigated over a
      period of 10 days. Enzyme treatment resulted in greater mass loss in
      microgravity, with nearly three times the loss of mass during Space Shuttle
      mission STS-62 compared to the stationary ground control. Clinorotation enhanced
      the loss of mass relative to a stationary control, but this increase was still
      significantly less than the increase with exposure to microgravity. This suggests
      the detrimental influence of turbulence on the enzyme function and the benefit of
      using microgravity to provide both low turbulence and uniformity of unequally
      dense materials within the reaction chamber. The results are considered for their
      general applicability to a variety of bioprocessing applications that may be
      enhanced in microgravity.

PMID- 18626939
TI  - Growth kinetics of a bacteriophage in continuous culture.
AB  - Lytic coliphage Qbeta was grown in continuously cultured host bacteria using a
      cascade of stirred flow reactors. The apparatus was constructed so that the
      steady stream of exponentially growing bacterial cells passing through the
      stirred flow reactors served to prevent coevolution brought about by host
      parasite interactions. Wall growth was the primary cause for deviation from ideal
      continuous culture conditions and is largely dependent on the surface structure
      of the host bacteria. Using an Escherichia coli strain deficient in adhesive type
      I pili expression, the desynchronization of single burst events could easily be
      followed over the course of four infection latency periods. Computer simulations
      based on a two-stage model for the Qbeta infection cycle were in perfect
      agreement with the experimental data. Applications of the optimized system to
      strategies of molecular evolution are discussed.

PMID- 18626940
TI  - Effects of pH and aeration on gamma-poly(glutamic acid) formation by Bacillus
      licheniformis in controlled batch fermentor cultures.
AB  - Bacillus licheniformis ATCC 9945A was grown on Medium E in batch fermentations in
      which the pH was maintained at 5.5., 6.5, 7.4, and 8.25. The effects of pH on
      cell growth, carbon source utilization, and gamma-polyglutamic acid (gamma-PGA)
      production, molecular weight, and polymer stereochemistry were determined. The
      gamma-PGA yield was highest (15 g/L, 96 h growth time) at pH 6.5. The increase in
      gamma-PGA formation at pH 6.5 corresponded with a relatively high specific
      production rate at high gamma-PGA concentration (0.09 h(-1), approximately 15 g/L
      gamma-PGA). In contrast, the specific gamma-PGA production rates at fermentor pH
      values of 5.5 and 7.4 decreased significantly for gamma-PGA fermentor yields >
      approximately 5 g/L. Interestingly, alteration of the medium pH had little to no
      significant effects on the product quality as measured by stereochemical
      composition and molecular weight. While glutamate and glycerol utilization were
      similar as a function of pH, citrate consumption increased at pH 6.5, indicating
      that the formation of gamma-PGA from citrate at pH 6.5 was of increased
      importance. The effect of aeration was evaluated by increasing the agitation
      speed (250 to 800 rpm) and aeration rate (0.5 to 2.0 L/min) at pH 6.5, the pH of
      maximal gamma-PGA production. Increased aeration resulted in doubling of the cell
      dry weights (2 to 4 g/L), increasing gamma-PGA yields (6.3 to 23 g/L by 48 h) and
      increasing in the maximum gamma-PGA-specific production rate (0.09 to 0.11 h(
      1)). Other effects of increased agitation included a rapid depletion of glutamate
      and citrate (by 50 h) and a decrease in product molecular weight. Despite the
      increase in agitation and aeration, oxygen limitation of the culture was not
      avoided, because the partial pressure decreased to <1.0% by 29 h.

PMID- 18626941
TI  - Studies on the synthesis of betahCG hormone in vero cells by recombinant vaccinia
      virus.

PMID- 18626944
TI  - Mobile larynx in Mongolian gazelle: Retraction of the larynx during rutting barks
      in male Mongolian gazelle (Procapra gutturosa Pallas, 1777).
AB  - This study provides the first evidence of pronounced temporary laryngeal descent
      in a bovid species. An elaborate acoustic display is prominent in male courtship
      behavior of polygynous Mongolian gazelle. During rut, rounding up of females is
      accompanied by continuous head-up barking by dominant males. Throughout the rut
      their evolutionarily enlarged larynx descends to a low mid-neck resting position.
      In the course of each bark the larynx is additionally retracted toward the
      sternum by 30% of the resting vocal tract length. A geometric model of active
      larynx movements was constructed by combining results of video documentation,
      dissection, skeletonization, and behavioral observation. The considerable
      distance between resting position and maximal laryngeal descent suggests a
      backward tilting of the hyoid apparatus and an extension of the thyrohyoid
      connection during the retraction phase. Return to the resting position is
      effected by strap muscles and by the elastic recoil of the pharynx and the
      thyrohyoid connection. An intrapharyngeal inflation of the peculiar palatinal
      pharyngeal pouch of adult males is inferred from a short-time expansion of the
      ventral neck region rostral to the laryngeal prominence. The neck of adult
      dominant males is accentuated by long gray guard hairs during the rut. The
      passive swinging of the heavy larynx of adult males during locomotion gives the
      impression of a handicap imposed on rutting males. Apparently, this disadvantage
      becomes outweighed by the profits for reproductive success.

PMID- 18626945
TI  - Ectopic dermal ridge configurations on the interdigital webbings and postaxial
      marginal portion of the hindlimb in Hammertoe mutant mice (Hm).
AB  - The effects of the hereditary malformation of Hammertoe mutant mice (gene symbol
      Hm) on the digital pads and dermal ridge configurations on their hindlimbs were
      examined. In the wild-type (+/+) mice with normally separated digits, dermal
      ridges developed only on the pads. Heterozygous (Hm/+) and homozygous (Hm/Hm)
      mutant mice, however, had a broad big toe, fused interdigital soft tissues,
      reduced claws, an extra rudimentary postaxial digit and camptodactyly. The dermal
      ridges appeared not only on the pads, affected in their number and
      configurations, but also on the ventral surface of the interdigital webbings and
      postaxial marginal area exhibiting an extra rudimentary digit and webbing. These
      aberrant configurations may be related to the abnormal occurrence of programmed
      cell death (PCD) in the interdigital zones and the postaxial marginal portion in
      Hm/+ and Hm/Hm mice. That is, the diminished cell death may fail to decrease the
      cell density in the interdigital zones and postaxial marginal portion and result
      in the webbing and an extra rudimentary digit and webbing, respectively.
      Simultaneously, it could also interrupt the migration of surviving cells of these
      areas toward the neighboring digits and the distal area of the sole and produce
      the ectopic dermal ridges on the way to the as yet unformed (presumptive) digital
      and plantar volar pads. The present findings suggest that normal interdigital and
      pre/postaxial PCD contributes not only to the separation of digits, the initial
      formation of individual digits of different sizes, and the inhibition of the
      extra digit but also to the development of the presumptive digital and plantar
      pads, including dermal ridges.

PMID- 18626943
TI  - Sox9 is expressed in mouse multipotent retinal progenitor cells and functions in
      Muller glial cell development.
AB  - It is widely accepted that the process of retinal cell fate determination is
      under tight transcriptional control mediated by a combinatorial code of
      transcription factors. However, the exact repertoire of factors necessary for the
      genesis of each retinal cell type remains to be fully defined. Here we show that
      the HMG-box transcription factor, Sox9, is expressed in multipotent mouse retinal
      progenitor cells throughout retinogenesis. We also find that Sox9 is
      downregulated in differentiating neuronal populations, yet expression in Muller
      glial cells persists into adulthood. Furthermore, by employing a conditional
      knockout approach, we show that Sox9 is essential for the differentiation and/or
      survival of postnatal Muller glial cells.

PMID- 18626946
TI  - Retinal ganglion cell inputs to the koniocellular pathway.
AB  - To understand the transmission of sensory signals in visual pathways we studied
      the morphology and central projection of ganglion cell populations in marmoset
      monkeys. Retinal ganglion cells were labeled by photofilling following injections
      of retrograde tracer in the lateral geniculate nucleus (LGN), or by intracellular
      injection with neurobiotin. Ganglion cell morphology was analyzed using
      hierarchical cluster analysis. In addition to midget and parasol ganglion cells,
      this method distinguished three main clusters of wide-field cells that correspond
      to small bistratified, sparse, and broad thorny cells identified previously. The
      small bistratified and sparse cells occupy neighboring positions on the
      hierarchical (linkage distance) tree. These cell types are presumed to carry
      signals originating in short-wavelength sensitive (S or "blue") cones in the
      retina. The linkage distance from these putative S-cone pathway ganglion cells to
      other wide-field cells is similar to the linkage distance from midget cells to
      parasol cells, suggesting that S-cone cells form a distinct functional subgroup
      of ganglion cells. Small bistratified cells and large sparse cells were the most
      commonly labeled wide-field cells following LGN injections in koniocellular layer
      K3. This is consistent with physiological evidence that the role of this layer
      includes transmission of S-cone signals to the visual cortex. Other wide-field
      cell types were also labeled following injections including K3, and other
      koniocellular LGN layers; these cell types may correspond to "non-blue
      koniocellular" receptive fields recorded in physiological studies.

PMID- 18626947
TI  - The impact of war-stress on MS exacerbations.

PMID- 18626948
TI  - Measurement of cytotoxic and interstitial components of cerebral edema in acute
      hepatic failure by diffusion tensor imaging.
AB  - PURPOSE: To use diffusion tensor imaging (DTI) metrics for measuring cytotoxic
      and interstitial components of cerebral edema (CE) in acute hepatic failure (AHF)
      patients. CE is a major complication in patients with AHF. MATERIALS AND METHODS:
      DTI was performed in 20 patients with AHF and 15 controls. Ten patients underwent
      repeat imaging after recovery from encephalopathy. Various regions of interest
      (ROIs) were drawn in the white and deep gray matter of the brain for the
      quantitation of fractional anisotropy (FA), mean diffusivity (MD), spherical
      isotropy (CS), linear anisotropy (CL), and planar anisotropy (CP) values.
      RESULTS: Significantly decreased MD values were observed in most brain ROIs in
      patients compared to controls. Significantly decreased FA, CL with increased CS
      values was also observed. In survivors with normal clinical profile after 3
      weeks, a significant increase in MD and FA values were associated with decreased
      CS values in some regions compared to baseline study; however, it was still
      significantly changed compared to controls. CONCLUSION: Decreased MD and
      increased CS associated with decreased FA represent cytotoxic and interstitial
      components of CE, respectively. Incomplete normalization of these metrics in
      survivors after 3 weeks clinical recovery may be due to incomplete metabolic
      recovery.

PMID- 18626950
TI  - Cell cycle analysis of foreign gene (beta-galactosidase) expression in
      recombinant mouse cells under control of mouse mammary tumor virus promoter.
AB  - The cell cycle dependency of foreign gene expression in recombinant mouse L cells
      was investigated. Two different recombinant mouse L cell lines having the
      glucocorticoid receptor-encoding gene and the lacZ reporter gene were used in
      this study. The lacZ gene expression was controlled by the glucocorticoid
      inducible mouse mammary tumor virus (MMTV) promoter in both cell lines. In "M4"
      cells the gr gene was under the control of another MMTV promoter, but in "R2"
      cells it was under the control of the constitutive Rous sarcoma virus promoter.
      These normally attachment-grown cells were adapted to suspension culture, and a
      dual-laser flow cytometer was used to simultaneously determine the DNA and
      foreign protein (beta-galactosidase) content of single living cells. Expression
      of beta-galactosidase as a function of cell cycle phase was evaluated for cells
      in exponential growth without any addition of the glucocorticoid inducer,
      dexamethasone. Cell cycle positions in the S phase were estimated on the basis of
      DNA content per cell, and position in the G1 phase was estimated on the basis of
      cell size as measured by pulse-width time of flight. The results showed that beta
      galactosidase synthesis occurred through all cell cycle phases, but the
      expression rate in the G1 phase was much lower than that in the S and G2/M phases
      in both cell lines. On the basis of cell size analysis, beta-galactosidase
      expression in M4 cells (with autoinducible promoter) was found to be higher than
      that in R2 cells (with inducible promoter) during the G1 phase.

PMID- 18626951
TI  - Mathematical modeling and analysis of monoclonal antibody production by hybridoma
      cells.
AB  - An attempt has been made to mathematically describe and analyze monoclonal
      antibody (MAB) productivity of hybridoma cells, with particular emphasis on
      continuous cultures under unsteady-state conditions. A simple and unstructured
      general kinetic model that takes account of productivity loss during long-term
      cultivation, cell proliferation, and the effects of nutrients and toxic products
      is proposed. The model is verified with data of continuous culture from five
      different cell lines under a wide range of experimental conditions. Analysis of
      these results showed that for a reliable assessment of effects of different
      factors and for comparison of kinetic data on MAB production it is important to
      consider possible loss of MAB productivity, the time dependence of which can be
      modeled by an exponential function plus a constant term. Variations of nutrient
      concentration, particularly that of glucose, glutamine, and serum, can
      significantly alter MAB production under certain conditions. These effects can be
      described in terms of saturation kinetic and/or noncompetitive inhibition
      kinetics.

PMID- 18626952
TI  - Efficient flotation of yeast cells grown in batch culture.
AB  - A fast flotation assay was used to select new floating yeast strains. The
      flotation ability did not seem to be directly correlated to total extracellular
      protein concentration of the culture. However, the hydrophobicity of the cell was
      definitely correlated to the flotation capacity. The Saccharomyces strains (FLT
      strains) were highly hydrophobic and showed an excellent flotation performance in
      batch cultures without additives (flotation agents) and with no need for a
      special flotation chamber or flotation column. A stable and well-organized
      structure was evident in the dried foam as shown by scanning electron microscopy
      which revealed its unique structure showing mummified cells (dehydrated) attached
      to each other. The attachment among the cells and the high protein concentration
      of the foams indicated that proteins might be involved in the foam formation. The
      floating strains (strains FLT) which were not flocculent and showed no tendency
      to aggregate, were capable of growing and producing ethanol in a synthetic medium
      containing high glucose concentration as a carbon source. The phenomenon
      responsible for flotation seems to be quite different from the flocculation
      phenomenon.

PMID- 18626953
TI  - Solvent effects on the catalytic activity of subtilisin suspended in organic
      solvents.
AB  - We studied a model transesterification reaction catalyzed by subtilisin Carlsberg
      suspended in toluene, n-hexane, diisopropyl ether, and mixtures of these
      solvents. To account for solvent effects due to differences in water partitioning
      between the enzyme and the bulk solvents, we measured water sorption isotherms
      for the enzyme in each solvent. We measured catalytic activity as a function of
      enzyme hydration and obtained bell-shaped curves with maxima at the same enzyme
      hydration in all the solvents. However, the activity maxima were different in all
      the media, being the lowest in toluene. Differences in the partitioning of
      substrates and product between the bulk solvent phase and the enzyme active site
      were accounted for but could not explain the lower catalytic activity observed in
      toluene. The fact that toluene is very similar to one of the substrates suggested
      the possibility of competitive inhibition by this solvent. We derived a model
      allowing for differences in solvation of the substrates, by using thermodynamic
      activities instead of concentrations, as well as for competitive inhibition by
      toluene. The model fit the experimental data well, confirming that toluene had a
      direct adverse effect on the catalytic activity of the enzyme.

PMID- 18626954
TI  - Optimization of the hydroxylamine cleavage of an expressed fusion protein to
      produce recombinant human insulin-like growth factor (IGF)-I.
AB  - The application of gene fusion technology for the production of heterologous
      proteins in Escherichia coli has required the development of specific cleavage
      methods to separate the coexpressed fusion protein partner from the protein of
      interest. When hydroxylamine is used to cleave Asn-Gly fusion protein linkages,
      undesirable chemical modification of asparagine and glutamine amino acids can
      also occur. In this study, hydroxylamine cleavage conditions were modified to
      minimize unwanted chemical heterogeneity that occurred during the cleavage of the
      fusion protein [Met(1)]-pGH(1-11)-Val-Asn-IGF-I (Long-IGF-I). The cleavage
      reaction was shown to be dependent on the hydroxylamine concentration,
      temperature, and pH. Optimal cleavage conditions were identified that resulted in
      very low levels of chemical heterogeneity, but under these mild conditions that
      cleavage of the labile Asn-Gly bond was reduced. Therefore, the reaction was
      further modified to improve the yield of IGF-I while minimizing chemical
      heterogeneity. The yield of unmodified IGF-I was improved from less than 25% to
      greater than 70%. Analysis of the heterogeneity produced using the modified
      cleavage technique showed that Asn(26) was converted to a hydroxamate. This
      variant was characterized in refolding and biological assays where it was
      equivalent to IGF-I. To further assess the effectiveness of the modified cleavage
      technique and to evaluate the potential for process scale-up, a gram-scale
      cleavage reaction of Long-IGF-I was carried out. The process yielded IGF-I with a
      low level of chemical heterogeneity that was easily removed by ion-exchange
      chromatography. Moreover, this work shows that the production of unmodified IGFs
      using hydroxylamine cleavage of fusion proteins is facilitated using the mild
      cleavage reaction.

PMID- 18626955
TI  - Deregulated expression of cloned transcription factor E2F-1 in Chinese hamster
      ovary cells shifts protein patterns and activates growth in protein-free medium.
AB  - Engineering of the cell cycle can be an effective means for bypassing growth
      factor requirements of animal cells. Cloned human E2F-1 from Nalm 6 cells was
      subcloned into pRc/CMV and transfected into Chinese hamster ovary (CHO) cells.
      Ten stable transfectant clones isolated from cells cultured under neomycin
      resistance selection pressure all expressed significantly higher amounts of E2F-1
      than control cells as determined by Western analysis. Confocal immunofluorescent
      microscopy and Southern analysis of several clones also provided evidence for the
      expression of cloned E2F-1 in these cells. CHO K1:E2F-1 cells are able to
      proliferate on well-defined serum- and protein-free basal medium and exhibit an S
      phase extended by 65% compared to CHO K1 cells mitogenically stimulated by basic
      fibroblast growth factor (bFGF). Two-dimensional electrophoresis of the
      intracellular proteins of E2F-1 clones shows an increase in 236 gene products
      compared to CHO K1 control cells, further verifying a functional regulatory role
      of cloned E2F-1 in CHO cells. Among these upregulated species is the cell cycle
      regulatory protein, cyclin A, which has already been shown to be regulated by E2F
      1 in human fibroblasts. Overexpression of cloned E2F-1 in CHO cells is a
      potentially useful new strategy for bypassing serum requirements in mammalian
      cell culture. Furthermore, such cell cycle control stimulus-protein pattern
      response data can contribute to a clearer understanding of complex multigene
      networks involved in mammalian cell cycle regulation.

PMID- 18626956
TI  - Extractive lactic acid fermentation in poly (ethyleneimine)-based aqueous two
      phase system.
AB  - The potential of an aqueous two-phase system composed of a polycation,
      poly(ethyleneimine) (PEI), and an uncharged polymer, (hydroxyethyl) cellulose
      (HEC), for extractive lactic acid fermentation was tested. Batch fermentation
      with 20 g/L glucose in two-phase medium using Lactococcus lactis without external
      pH control resulted in 3-4 times higher amount of lactate and biomass produced as
      compared to that in a conventional one-phase medium. Lactic acid was
      preferentially partitioned to the PEI-rich bottom phase. However, the cells which
      favored the HEC-rich top phase in a fresh two-phase medium were partitioned to a
      significant extent to the bottom phase after fermentation. Addition of phosphate
      buffer or pH adjustment to 6.5 after fermentation caused fewer cells to move to
      the bottom phase. With external pH control, fermentation in normal and two-phase
      medium showed no marked differences in glucose consumption and lactic acid yield,
      except that about 1.3 times higher cell density was obtained in the two-phase
      broth, especially at initial glucose concentrations of 50-100 g/L. Use of higher
      concentration of phosphate during batch fermentation in the two-phase medium with
      50 g/L sugar provided a 15% higher yield of lactic acid, but the growth rate of
      cells was nearly half of the normal, thus affecting the productivity. Continuous
      fermentation with twice the normal phosphate concentration resulted in higher
      cell density, product yield, and productivity in two-phase medium than in
      monophasic medium.

PMID- 18626957
TI  - Medium design based on stoichiometric analysis of microbial transglutaminase
      production by Streptoverticillium mobaraense.
AB  - A stoichiometric model was developed for the application of medium design in
      microbial transglutaminase production by Streptoverticillium mobaraense. The
      model avoids dealing with all the metabolic reactions involved by simply lumping
      them into a single reaction. With the help of measurement results, an analysis of
      the nutrients' roles, and biochemical knowledge of the microorganism, all
      stoichiometric coefficients in the model were calculated. These coefficients were
      used for medium design. With this designed medium, microbial transglutaminase
      activity was increased fourfold, compared to that in the basal medium.

PMID- 18626958
TI  - Metabolic flux analysis of hybridoma cells in different culture media using mass
      balances.
AB  - The estimation of the intracellular fluxes of mammalian cells using only the mass
      balances of the relevant metabolites is not possible because the set of linear
      equations defined by these mass balances is underdetermined. Either additional
      experimental flux data or additional theoretical constraints are required to find
      one unique flux distribution out of the solution space that is bound by the mass
      balances. Here, a method is developed using the latter approach. The uptake and
      production rates of amino acids, glucose, lactate, O(2), CO(2), NH(4), MAB, and
      the intracellular amino acid pools have been determined for two different steady
      states. The cellular composition {total protein and protein composition, total
      lipids and fatty acid distribution, total carbohydrates, DNA and RNA} has been
      measured to calculate the requirements for biosynthesis. It is shown to be
      essential to determine the uptake/production rates of ammonia and either carbon
      dioxide or oxygen. In mammalian cells these are cometabolites of cyclic metabolic
      pathways. The flux distribution that is found using the Euclidean minimum norm as
      the additional theoretical constraint and taking either the CO(2) or the NAD(P)H
      mass balance into account is shown to be in agreement with the measured O(2) and
      CO(2) metabolic rates.The metabolic fluxes in hybridoma cells in continuous
      culture at a specific growth rate of 0.83 day(-1) are estimated for a medium with
      (optimal medium) and without (suboptimal medium) Primatone RL, an enzymatic
      hydrolysate of animal tissue that causes a more than twofold increase in cell
      density. It is concluded that (i)The majority of the consumed glucose (>90%) is
      channeled through the pentose-phosphate pathway in rapidly proliferating
      cells.(ii)Pyruvate oxidation and tricarboxylic acid (TCA) cycle activity are
      relatively low, i.e., 8% of the glucose uptake in suboptimal and 14% in optimal
      medium, respectively. Under both conditions, only a small fraction of pyruvate is
      further oxidized to CO(2).(iii)The flux from glutamate to alpha-ketoglutarate
      (catalyzed by glutamate dehydrogenase) is almost zero in medium with and even
      slightly reversed in medium without Primatone RL. Almost all glutamate enters the
      TCA cycle due to the action of transaminases.(iv)Transhydrogenation plays a
      significant role in hybridoma cells under our experimental conditions. NADPH is
      produced at relatively high rates (11 x 10(-12) to 13 x 10(-12) mol . cell(-1) .
      day(-1)) compared to other fluxes in both culture media.

PMID- 18626959
TI  - Membrane fouling in sterile filtration of recombinant human growth hormone.
AB  - The most troublesome problem encountered during the sterile filtration of protein
      solutions is membrane fouling. This article presents our study on sterile
      filtration of a model protein, recombinant human growth hormone (rhGH). Scanning
      electron microscopy (SEM) analysis shows that 0.22-mum membranes, when used to
      filter the mannitol-formulated protein solution under a 0.35-bar transmembrane
      pressure, were plugged to a great extent. When zinc ions were added to induce
      aggregates, the fouling tendency of rhGH solutions increased with increasing
      amount and size of the aggregates, indicating that the aggregates present before
      filtration might be responsible for membrane fouling. However, repeated
      filtration of the same solution using a fresh filter each time cannot reduce
      membrane fouling, and all filtrates contain the same trace amount of hGH
      particulates as the prefiltered solution. Particulate size was determined to be
      between 0.03 and 0.15 mum by dynamic light scattering. Also, in view of the fact
      that protein formulations significantly affected the tendency of fouling with the
      same preexisting aggregates, it is likely that fouling was more attributed to the
      aggregation taking place in the filter pores during filtration (secondary
      aggregation) than to the aggregates present before filtration. Adding a
      surfactant to or increasing the pH of the protein solution improves the
      filtration, whereas increasing ionic strength slows down the filtration. This
      result suggests that the balance of the protein's interaction and electrostatic
      repulsion plays an important role in the protein's fouling tendency. Many factors
      might change the microenvironment in the pores and disturb this balance. Those
      considerations and the aggregation tendency of rhGH in the filter pores will be
      discussed in detail separately.

PMID- 18626960
TI  - Active-site titration of serine proteases in organic solvents.
AB  - Calculation of kinetic constants of an enzymatic reaction in organic solvents
      requires knowledge of the functional active-site concentration in organic
      solvents, and this can be significantly different than that in water. An
      experimental method for active-site titration of serine proteases in organic
      media has been developed based on the kinetics of inhibition by
      phenylmethanesulfonyl fluoride (PMSF), a serine-specific inhibitor (or suicide
      substrate). This kinetic approach is fundamentally different from other
      techniques that require complete titration of all accessible enzyme active sites.
      This active site titration method was applied to subtilisins BPN' and Carlsberg
      and alpha-chymotrypsin and resulted in fractions of active sites that ranged from
      8 to 62% (of the fraction active in water) depending on the enzyme, the method of
      enzyme preparation, and the organic solvent used. The active-site concentration
      of subtilisin BPN' and Carlsberg increased with increasing hydrophobicity of the
      solvent and with increasing solvent hydration in tetrahydrofuran. The dependence
      of the fraction of active sites on the nature of the organic solvent appears to
      be governed largely by solvent-induced inactivation caused by direct interaction
      of a hydrophilic solvent with the enzyme.

PMID- 18626961
TI  - Two-dimensional electrophoresis of proteins as a tool in the metabolic
      engineering of cell cycle regulation.
AB  - Metabolic engineering of cell cycle regulation addresses important
      biotechnological problems about serum removal from animal cell culture systems.
      Chinese hamster ovary cells stimulated to grow by fetal calf serum, insulin, or
      basic fibroblast growth factor were studied by two-dimensional electrophoresis
      (2DE) and the resulting protein expression patterns were analyzed. Detailed 2DE
      protocols are provided and at least 24 gene products are identified which may
      play an important role in growth factor signaling. Moreover, a correlation
      between the expression of three proteins (cyclin D1, cyclin E, and E2F-1) and
      mitogenic strength was found.

PMID- 18626962
TI  - Expression of active spinach glycolate oxidase in Aspergillus nidulans.
AB  - The biocatalytic production of glyoxylic acid from glycolic acid requires two
      enzymes: glycolate oxidase, which catalyzes the oxidation of glycolic acid by
      oxygen to produce glyoxylic acid and hydrogen peroxide, and catalase, which
      decomposes the byproduct hydrogen peroxide. As an alternative to isolation from
      the leaf peroxisomes of spinach, glycolate oxidase has now been cloned and
      expressed in transformants of Aspergillus nidulans T580 at levels ranging from
      1.7 to 36 IU/g dry wt. cells. The glycolate oxidase of transformant strain T17
      comprises ca. 1.9% of total cell protein and is expressed at near 100% activity.

PMID- 18626963
TI  - Development of extraintestinal manifestations in pediatric patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Extraintestinal manifestations (EIMs) in pediatric patients with
      inflammatory bowel disease (IBD) are poorly characterized. We examined the
      prevalence of EIMs at diagnosis, subsequent incidence, and risk factors for EIMs.
      METHODS: Data for 1649 patients from the PediIBD Consortium Registry, diagnosed
      with IBD before 18 years of age (1007 [61%] with Crohn's disease, 471 [29%] with
      ulcerative colitis, and 171 [10%] with indeterminate colitis), were analyzed
      using logistic regression, Kaplan-Meier, log rank tests, and Cox models. RESULTS:
      EIMs were reported prior to IBD diagnosis in 97 of 1649 patients (6%). Older
      children at diagnosis had higher rates compared with younger children, and
      arthritis (26%) and aphthous stomatitis (21%) were most common. Among the 1552
      patients without EIM at diagnosis, 290 developed at least 1 EIM. Kaplan-Meier
      estimates of cumulative incidence were 9% at 1 year, 19% at 5 years, and 29% at
      15 years after diagnosis. Incidence did not differ by IBD type (P = 0.20), age at
      diagnosis (P = 0.22), or race/ethnicity (P = 0.24). Arthritis (17%) and
      osteopenia/osteoporosis (15%) were the most common EIMs after IBD diagnosis.
      CONCLUSIONS: In our large cohort of pediatric IBD patients, 6% had at least 1 EIM
      before diagnosis of IBD. At least 1 EIM will develop in 29% within 15 years of
      diagnosis. The incidence of EIMs both before and after diagnosis of IBD differs
      by type of EIM and may be slightly higher in girls, but is independent of the
      type of IBD, age at diagnosis, and race/ethnicity.

PMID- 18626964
TI  - Paraoxonase-1 status in Crohn's disease and ulcerative colitis.
AB  - BACKGROUND: Paraoxonase 1 (PON1) is an extracellular enzyme, which in the
      gastrointestinal tract may act as a local detoxifier, antioxidant,
      immunomodulator, and/or quorum-quenching factor. There are no data on PON1
      activity in Crohn's disease (CD). METHODS: PON1 phenotype and activity were
      determined spectrophotometrically in 52 subjects with CD, 67 with ulcerative
      colitis (UC), and 99 healthy individuals, and related to lipid peroxidation and
      disease phenotype, clinical and biochemical activity, and therapeutic strategy.
      Diagnostic utility of PON1 was evaluated by ROC analysis and compared with C
      reactive protein (CRP). RESULTS: In comparison with controls (166 U), PON1 was
      reduced only in active CD (110 U, P < 0.0001) and UC (126 U, P < 0.0001), and
      correlated with disease activity (r = -0.47, P = 0.001 in CD and r = -0.50, P <
      0.001 in UC). PON1 significantly correlated with erythrocyte sedimentation rate
      (ESR) (r = -0.36), platelets (r = -0.35), interleukin-6 (r = -0.45), hemoglobin
      (r = 0.29), transferrin (r = 0.46), albumin (r = 0.60) in CD, and CRP (r = 
      0.29), ESR (r = -0.37), platelets (r = -0.43), leukocytes (r = -0.50),
      interleukin-6 (r = -0.45), hemoglobin (r = 0.34), transferrin (r = 0.54), and
      albumin (r = 0.50) in UC. PON1 correlated positively with lipids but not with
      their peroxidation markers (thiobarbituric acid-reactive substances, lipid
      hydroperoxides, ox-LDL, and ox-LDL autoantibodies). PON1 phenotype B (protective
      against IBD) tended to be less frequent in IBD patients than controls, and
      associated with lower concentration of inflammatory indices. PON1 was a poorer
      indicator of CD or UC than CRP. CONCLUSIONS: PON1 was reduced in IBD, despite
      treatment with antioxidant 5'-aminosalicylate derivatives. PON1 reflected disease
      activity, inflammation severity, and anemia but not lipid peroxidation. The
      diagnostic power of PON1 was insufficient for its clinical application.

PMID- 18626965
TI  - Molecular bases of impaired water and ion movements in inflammatory bowel
      diseases.
AB  - The intestine is dedicated to the absorption of water and nutrients. Fine tuning
      of this process is necessary to maintain an adequate balance and inflammation
      disrupts the equilibrium. This review summarizes the current evidence in this
      field. Classical mechanisms proposed include alteration of epithelial integrity,
      augmented secretion, and reduced absorption. In addition, intestinal inflammation
      is associated with defects in epithelial barrier function. However, our
      understanding of the phenomenon has been complicated by the fact that ionic
      secretion is in fact diminished in vivo, even after inflammation has subsided.
      Inhibited ionic secretion can be reversed partially or totally in vitro by
      maneuvers such as blockade of inducible nitric oxide synthase or removal of the
      submucosal layer. Disturbances in ionic absorption are less well characterized
      but clearly involve both electroneutral and electrogenic Na(+) absorption.
      Altered ionic transport is associated with changes in the expression and function
      of the transporters, including the Na(+)/K(+) ATPase, the
      sodium/potassium/chloride cotransporter 1 (NKCC1), the sodium/hydrogen exchanger
      3 (NHE3), and the epithelial sodium channel (ENaC), as well as to the modulation
      of intracellular signaling. Further investigation is needed in this area in order
      to provide an integrated paradigm of ionic transport in the inflamed intestine.
      In particular, we do not know exactly how diarrhea ensues in inflammation and,
      consequently, we do not have specific pharmacological tools to combat this
      condition effectively and without side effects. Moreover, whether transport
      disturbances are reversible independently of inflammatory control is unknown.

PMID- 18626966
TI  - Psychoendocrine and physical performance responses in male Tunisian rugby players
      during an international competitive season.
AB  - The aim was to investigate a follow-up study based on hormonal, physical, and
      psychological parameters among rugby players who trained during a whole season
      interspersed with competitions on an international level. Fitness or reciprocally
      tiredness as well as competitive anxiety were evaluated, respectively, using the
      French Society for Sports Medicine (SFMS) and the sport competition anxiety test
      (SCAT) questionnaires. In this study, SFMS and SCAT scores increased respectively
      over the competitive season. The SFMS score revealed a state of relative
      tiredness at the end of the season, highlighted by a slight decrement in physical
      performances. The SCAT score changes are related to the competition context and
      therefore increased accordingly to the importance of the competition stake. We
      analyzed the corticotrope and the gonadotrope axis before (T(1)), and at the end
      of the national and international rugby season (T(2)). Training did not affect
      the resting salivary cortisol (Csal) levels, but induced a decrease in resting
      testosterone (Tsal) values, resulting in a dropped T/C ratio. Competition, in
      both periods (T(1)-T(2)), provoked a significant increase in Csal levels, but the
      Tsal responses depended on the match stake. Their concentrations increased when
      the competition generated an important stress and decreased when the
      psychological conditions remained relatively stable. SFMS is preferentially
      correlated with resting Csal levels and T/C values measured at 08:00 hr but not
      with Tsal. SCAT is highly correlated with competitive Csal and Tsal
      concentrations measured before and after the matches.

PMID- 18626967
TI  - Management of the pregnant IBD patient.
AB  - Women with inflammatory bowel disease (IBD) and the physicians who care for them
      must make difficult decisions on issues of conception, pregnancy, and
      breastfeeding with very limited and often contradictory information. This review
      provides the most current information on the inheritance of IBD, fertility,
      pregnancy outcomes, the management of disease during pregnancy, and the safety of
      medications in pregnancy and breastfeeding. We would like to emphasize that the
      information presented here must be individualized to the specific situation of
      each patient, their acceptance of risk, and their degree of disease severity.

PMID- 18626968
TI  - Melatonin and ulcerative colitis: evidence, biological mechanisms, and future
      research.
AB  - Ulcerative colitis (UC) is an inflammatory bowel disease that afflicts up to 1
      million people in the US. Current treatments for UC are mostly nonspecific, not
      always effective, and often accompanied by serious side effects. Therefore, there
      is considerable interest in finding alternative and more tolerable treatments for
      this disease. Physiologic data suggest that melatonin is an important regulator
      of both inflammation and motility in the gastrointestinal tract, and data from in
      vitro studies, animal experiments, and limited studies in humans suggest that
      supplemental melatonin may have an ameliorative effect on colitis. In this review
      we summarize the evidence regarding melatonin as a possible therapeutic agent in
      UC and discuss possible biological mechanisms and directions for future research.

PMID- 18626969
TI  - Glatiramer acetate: a novel therapeutic approach in Crohn's disease?

PMID- 18626970
TI  - Exceptional diversity of mouse lemurs (Microcebus spp.) in the Makira region with
      the description of one new species.
AB  - Although the number of described lemur species has increased considerably over
      the last 20 years, detailed biogeographic data are still lacking from many
      geographic regions, in particular in the eastern part of Madagascar. This study
      investigated mouse lemur species diversity in a previously unstudied Inter-River
      System in the eastern Makira region. Three sites were visited and 26 individuals
      were sampled and characterized with 13 external morphometric measurements.
      Standard phylogenetic analyses were performed on the basis of sequences of three
      mitochondrial loci by including representatives of all other published mouse
      lemur species for comparison. The analyses revealed the presence of three mouse
      lemur species in one study site, two of which were previously undescribed. The
      two new species are genetically distinct and belong to the larger-bodied mouse
      lemur species on the island, whereas the third species, Microcebus mittermeieri,
      belongs to the smaller-bodied mouse lemur species. The study fully describes one
      of the new species. This study and other lemur inventories suggest that the
      Makira region is particularly rich in lemur species and the lack of any protected
      zone in this area should now attract the urgent attention of conservation
      stakeholders.

PMID- 18626971
TI  - Postpartum recuperation in primiparous rhesus macaques and development of their
      infants.
AB  - Female primates endure great costs during pregnancy and lactation. Some studies
      have been conducted on exploring these; however, information on how maternal
      condition before conception influences maternal postpartum recuperation and
      infant development are not well known, especially in primipares. This 2-year
      investigation explored how maternal condition, maternal foraging time and alert
      time, and infants' time on nipple influenced postpartum recovery of primiparous
      rhesus macaques, as well as their infant's development during the first 3 months
      postpartum. The study was conducted on 11 female rhesus macaques (Macaca mulatta)
      living at the Caribbean Primate Research Center, Sabana Seca Field Station,
      Puerto Rico. Infant survivorship and development were not influenced by maternal
      age at first parturition or by the infants' time on the nipple. Infant
      development and maternal recovery were influenced by maternal condition before
      conception. Older primipares demonstrated greater postpartum recuperation.
      Maternal postpartum recuperation was not influenced by maternal feeding time or
      time the infant spent on the nipple. Maternal recuperation was negatively
      correlated with increased vigilance (alert time).

PMID- 18626972
TI  - Interplay between inflammation and degeneration: using inclusion body myositis to
      study "neuroinflammation".

PMID- 18626973
TI  - Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients.
AB  - OBJECTIVE: Detailed analysis of phenotypic and molecular genetic aspects of Dok-7
      myasthenia in 16 patients. METHODS: We assessed our patients by clinical and
      electromyographic studies, by intercostal muscle biopsies for in vitro
      microelectrode analysis of neuromuscular transmission and quantitative electron
      microscopy EM of 409 end plates (EPs), and by mutation analysis, and expression
      studies of the mutants. RESULTS: The clinical spectrum varied from mild static
      limb-girdle weakness to severe generalized progressive disease. The synaptic
      contacts were single or multiple, and some, but not all, were small. In vitro
      microelectrode studies indicated variable decreases of the number of released
      quanta and of the synaptic response to acetylcholine; acetylcholine receptor
      (AChR) channel kinetics were normal. EM analysis demonstrated widespread and
      previously unrecognized destruction and remodeling of the EPs. Each patient
      carries 2 or more heteroallelic mutations: 11 in genomic DNA, 7 of which are
      novel; and 6 identifiable only in complementary DNA or cloned complementary DNA,
      3 of which are novel. The pathogenicity of the mutations was confirmed by
      expression studies. Although the functions of Dok-7 include AChR beta-subunit
      phosphorylation and maintaining AChR site density, patient EPs showed normal AChR
      beta-subunit phosphorylation, and the AChR density on the remaining junctional
      folds appeared normal. INTERPRETATION: First, the clinical features of Dok-7
      myasthenia are highly variable. Second, some mutations are complex and
      identifiable only in cloned complementary DNA. Third, Dok-7 is essential for
      maintaining not only the size but also the structural integrity of the EP.
      Fourth, the profound structural alterations at the EPs likely contribute
      importantly to the reduced safety margin of neuromuscular transmission.

PMID- 18626974
TI  - Spider silk aging: initial improvement in a high performance material followed by
      slow degradation.
AB  - Spider silk possesses a unique combination of high tensile strength and
      elasticity resulting in extraordinarily tough fibers, compared with the best
      synthetic materials. However, the potential application of spider silk and
      biomimetic fibers depends upon retention of their high performance under a
      variety of conditions. Here, we report on changes in the mechanical properties of
      dragline and capture silk fibers from several spider species over periods up to 4
      years of benign aging. We find an improvement in mechanical performance of silk
      fibers during the first year of aging. Fibers rapidly decrease in diameter,
      suggesting an increase in structural alignment and organization of molecules. One
      year old silk also is stiffer and has higher stress at yield than fresh silk,
      whereas breaking force, elasticity, and toughness either improve or are
      unaffected by early aging. However, 4-year old silk shows signs of degradation as
      the breaking load, elasticity, and toughness are all lower than in fresh silk.
      Aging, however, does not reduce the tensile strength of silk. These data suggest
      initially rapid reorganization and tighter packaging of molecules within the
      fiber, followed by longer-term decomposition. We hypothesize that possibly the
      breakdown of amino acids via emission of ammonia gas, as is seen in long-term
      aging of museum silkworm fabrics, may contribute. Degradation of spider silk
      under benign conditions may be a concern for efforts to construct and utilize
      biomimetic silk analogs. However, our findings suggest an initial improvement in
      mechanical performance and that even old spider silk still retains impressive
      mechanical performance.

PMID- 18626975
TI  - Mechanisms of action of probiotics: recent advances.
AB  - The intestinal microbiota plays a fundamental role in maintaining immune
      homeostasis. In controlled clinical trials probiotic bacteria have demonstrated a
      benefit in treating gastrointestinal diseases, including infectious diarrhea in
      children, recurrent Clostridium difficile-induced infection, and some
      inflammatory bowel diseases. This evidence has led to the proof of principle that
      probiotic bacteria can be used as a therapeutic strategy to ameliorate human
      diseases. The precise mechanisms influencing the crosstalk between the microbe
      and the host remain unclear but there is growing evidence to suggest that the
      functioning of the immune system at both a systemic and a mucosal level can be
      modulated by bacteria in the gut. Recent compelling evidence has demonstrated
      that manipulating the microbiota can influence the host. Several new mechanisms
      by which probiotics exert their beneficial effects have been identified and it is
      now clear that significant differences exist between different probiotic
      bacterial species and strains; organisms need to be selected in a more rational
      manner to treat disease. Mechanisms contributing to altered immune function in
      vivo induced by probiotic bacteria may include modulation of the microbiota
      itself, improved barrier function with consequent reduction in immune exposure to
      microbiota, and direct effects of bacteria on different epithelial and immune
      cell types. These effects are discussed with an emphasis on those organisms that
      have been used to treat human inflammatory bowel diseases in controlled clinical
      trials.

PMID- 18626976
TI  - IL-23R determines susceptibility in Crohn's disease in a Mediterranean area.

PMID- 18626977
TI  - Evidence for a role of epithelial mesenchymal transition during pathogenesis of
      fistulae in Crohn's disease.
AB  - BACKGROUND: The pathogenesis of fistulae in Crohn's disease (CD) patients is
      barely understood. We recently showed that more than two-thirds of CD fistulae
      are covered with flat, mesenchymal-like cells (transitional cells [TC]) forming a
      patchy basement membrane. Epithelial-to-mesenchymal transition (EMT) is a process
      of reprogramming epithelial cells, allowing them to migrate more effectively and
      giving epithelial cells an "invasive" potential. EMT has been suggested to be
      crucial in fibrosis found in different tissues and diseases. We therefore
      investigated whether EMT could be involved in the pathogenesis of fistulae
      formation in CD. METHODS: In all, 18 perianal fistulae, 2 enteroenteric, and 1
      enterovesical fistulae from 17 CD patients were analyzed. In addition 2 perianal
      fistulae of non-CD patients were studied. Hematoxylin and eosin staining,
      immunohistochemistry for the expression of cytokeratins 8 and 20, beta6-integrin,
      E-cadherin, beta-catenin, vimentin, and TGF-beta1 and 2 were performed according
      to standard techniques. RESULTS: The TC covering perianal or enteroenteric
      fistulae were strongly positive for cytokeratins 8 and 20 but negative for
      vimentin, indicating their epithelial origin. beta6-Integrin and TGF-beta had the
      highest staining intensities in the transitional zone between the epithelium and
      the TC. Expression of junctional proteins such as E-cadherin was reduced in TC as
      compared to regular fistulae epithelium. In addition, a translocation of beta
      catenin from the membrane to the cytoplasm was observed. CONCLUSIONS: Our data
      for the first time indicate an expression pattern of epithelial and mesenchymal
      markers in TC associated with fistulae formation that is characteristic for EMT.
      Studying the pathways of EMT during intestinal fistulae formation may help to
      develop new therapeutic strategies.

PMID- 18626978
TI  - Colonic involvement does not predispose to thrombosis in IBD.

PMID- 18626979
TI  - Spectrum and frequency of ophthalmologic manifestations in patients with
      inflammatory bowel disease: a prospective single-center study.
AB  - BACKGROUND: The frequency and spectrum of ophthalmologic manifestations in
      patients with inflammatory bowel disease (IBD) has been reported to vary among
      studies; however, rare and silent manifestations have not been extensively
      studied. METHODS: This was a prospective study of 60 patients diagnosed with IBD
      who underwent full ophthalmologic examination, including visual acuity, slit lamp
      examination of the anterior segments, intraocular pressure, and fundus
      examination accompanied by color photography. Thirty-seven (61,7%) patients were
      diagnosed with ulcerative colitis (UC) and 23 (38,3%) with Crohn's disease (CD).
      Data from 276 control individuals were used for the determination of the
      prevalence of dry eye in our area. RESULTS: Ophthalmologic manifestations were
      diagnosed in 26 (43%) patients (14 UC, 12 CD; 12 males and 14 females).
      Conjunctivitis was diagnosed in 1 patient (CD), episcleritis in 2 patients (UC),
      and iridocyclitis in 3 (CD). Fundus examination showed 1 patient (CD) with
      unilateral choroiditis, 1 (UC) with retinal vasculitis, and 1 (CD) with optic
      neuritis. Retinal pigment epithelium disturbances (RPED) were present in 3
      patients (1 CD, 2 UC) and 2 had serous retinal detachment. In total, 13/60
      patients (22%) had dry eye compared with the 11% prevalence in controls. Eight
      patients developed glucocorticosteroid-induced cataracts, 2 of them treated
      surgically. CONCLUSIONS: This study demonstrated the prevalence of the spectrum
      of ophthalmologic manifestations in the IBD population, including some rare and
      silent findings that may merit consideration and early intervention.

PMID- 18626982
TI  - Tissue engineering, bioartificial organs, and cell therapies: I.

PMID- 18626980
TI  - Adjustment to inflammatory bowel disease: the relative influence of illness
      perceptions and coping.
AB  - BACKGROUND: The Common Sense Model (CSM) of illness representations was used in
      the current study to examine the relative contribution of illness perceptions and
      coping strategies in explaining adjustment to inflammatory bowel disease (IBD).
      METHODS: Participants were 80 adults consecutively attending an outpatients'
      clinic with a diagnosis of either Crohn's disease or ulcerative colitis.
      Respondents completed and returned a questionnaire booklet that assessed illness
      perceptions, coping, and adjustment. Adjustment was measured from the
      perspectives of psychological distress, quality of life, and functional
      independence. RESULTS: Illness perceptions (particularly perception of
      consequences of IBD) were uniformly the most consistent variables explaining
      adjustment to IBD. Coping did not significantly add to predicting adjustment once
      illness perceptions were controlled for and therefore did not mediate the
      relationship between illness perceptions and adjustment, as proposed in the CSM.
      CONCLUSIONS: The results suggest the importance of addressing illness perceptions
      in developing appropriate psychological interventions for IBD.

PMID- 18626983
TI  - Fibroblast aggregation by suspension with conjugates of poly(ethylene glycol) and
      RGD.
AB  - Cell aggregates may be useful components of artificial organs and mammalian cell
      bioreactors, but many cells do not naturally aggregate. In a previous report,(4)
      we described a method for promoting neural cell aggregation by addition of water
      soluble conjugates of cell adhesion peptides, containing the three amino acid
      sequence Arg-Gly-Asp (RGD), and poly(ethylene glycol) (PEG). Here, we examined
      the mechanism of conjugate-induced aggregation using fibroblasts and a variety
      PEG-peptide conjugates. Aggregation was monitored during rotation culture of
      fibroblasts in the presence of unconjugated GRGDY and PEG; monofunctional (PEG
      GRGDY) and bifunctional (GRGDY-PEG-GRGDY) conjugates; and bifunctional conjugates
      produced with a similar, but non-cell-binding, peptide (GRGEY-PEG-GRGEY). GRGDY
      PEG-GRGDY conjugates induced rapid and pronounced fibroblast aggregation that was
      dose-dependent; at the highest concentration tested (5 mg/mL GRGDY-PEG-GRGDY),
      cell aggregates were produced more quickly ( approximately 1 h) and were
      significantly larger at 24 h (mean radius approximately 66 mum) than at slightly
      lower concentrations (1.7 and 3.3 mg/mL). Aggregation with GRGDY-PEG-GRGDY was
      completely inhibited by dissolved GRGDY (1.7 mg/mL). Neither unmodified GRGDY,
      unmodified PEG, PEG-GRGDY, nor GRGEY-PEG-GRGEY conjugates led to significant
      aggregation. The extent of aggregation depended on PEG molecular weight:
      conjugates with 3400 M(w) PEG produced aggregates with significantly larger mean
      radius than conjugates with 20,000 M(w) PEG. When 1N-8A fibroblasts, genetically
      engineered to produce recombinant nerve growth factor (NGF), were aggregated with
      GRGDY-PEG-GRGDY, aggregated cells produced more NGF per cell than nonaggregated
      cells. Aggregation of cells may lead to improved cell function, such as the
      increase in NGF production observed here, which could be useful in large-scale
      cell culture and construction of artificial organs or tissue transplants for
      tissue engineering. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626984
TI  - Review: Hydrogels for cell immobilization.
AB  - Hydrogels are being investigated for mammalian cell immobilization. Their
      material properties can be engineered for biocompatibility, selective
      permeability, mechanical and chemical stability, and other requirements as
      specified by the application including uniform cell distribution and a given
      membrane thickness or mechanical strength. These aqueous gels are attractive for
      analytical and tissue engineering applications and can be used with
      immobilization in therapies for various diseases as well as to generate
      bioartificial organs. Recent advances have broadened the use of hydrogel cell
      immobilization in biomedical fields. To provide an overview of available
      technology, this review surveys the current developments in immobilization of
      mammalian cells in hydrogels. Discussions cover hydrogel requirements for use in
      adhesion, matrix entrapment, and microencapsulation, the respective processing
      methods, as well as current applications. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626985
TI  - Transport characterization of hydrogel matrices for cell encapsulation.
AB  - Current membrane-based bioartificial organs consist of three basic components:
      (1) a synthetic membrane, (2) cells that secrete the product of interest, and (3)
      an encapsulated matrix material. Alginate and agarose have been widely used to
      encapsulate cells for artificial organ applications. It is important to
      understand the degree of transport resistance imparted by these matrices in cell
      encapsulation to determine if adequate nutrient and product fluxes can be
      obtained. For artificial organs in xenogeneic applications, it may also be
      important to determine the extent of immunoprotection offered by the matrix
      material. In this study, diffusion coefficients were measured for relevant
      solutes [ranging in size from oxygen to immunoglobulin G (IgG)] into and out of
      agarose and alginate gels. Alginate gels were produced by an extrusion/ionic
      crosslinking process using calcium while agarose gels were thermally gelled. The
      effect of varying crosslinking condition, polymer concentration, and direction of
      diffusion on transport was investigated. In general, 2-4% agarose gels offered
      little transport resistance for solutes up to 150 kD, while 1.5-3% alginate gels
      offered significant transport resistance for solutes in the molecular weight
      range 44-155 kD-lowering their diffusion rates from 10- to 100-fold as compared
      to their diffusion in water. Doubling the alginate concentration had a more
      significant effect on hindering diffusion of larger molecular weight species than
      did doubling the agarose concentration. Average pore diameters of approximately
      170 and 147 A for 1.5 and 3% alginate gels, respectively, and 480 and 360 A for 2
      and 4% agarose gels, respectively, were estimated using a semiempirical
      correlation based on diffusional transport of different-size solutes. The method
      developed for measuring diffusion in these gels is highly reproducible and useful
      for gels crosslinked in the cylindrical geometry, relevant for studying transport
      through matrices used in cell immobilization in the hollow fiber configuration.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18626986
TI  - Stability of hydrogels used in cell encapsulation: An in vitro comparison of
      alginate and agarose.
AB  - The present studies were undertaken to evaluate the in vitro gel stability of the
      hydrogels alginate and agarose. Gel strength (of alginate and agarose) and
      protein diffusion (of alginate only) were shown to correlate with gel stability
      and to be useful techniques to monitor gel stability over time. The gel strengths
      of alginate and agarose were followed for a 90-day period using gel strength as a
      measure of gel stability. The gel strength of agarose diminished in the presence
      of cells because the cells likely interfered with the hydrogen bond formation
      required for agarose gelation. In the presence of cells, the gel strength of
      agarose decreased by an average of 25% from time 0 to 60 days, thereafter
      maintaining that value to 90 days. The gel strength of calcium- or barium
      crosslinked alginate decreased over 90 days, with an equilibrium gel strength
      being achieved after 30 days. The presence of cells did not further decrease
      alginate gel strength. The gel strengths of calcium- and barium-crosslinked
      alginates were similar at 60 days-350 +/- 20 g and 300 +/- 60 g, respectively
      indicating equivalence in their stability. The stability of calcium-crosslinked
      sodium alginate gels over a 60-day time period was monitored by diffusion of
      proteins ranging in molecular weight from 14.5 to 155 kD. From these diffusion
      measurements, the average pore size of the calcium-crosslinked alginate gels was
      estimated, using a semi-empirical model, to increase from approximately 176 to
      289 A over a period of 60 days. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626987
TI  - Review: Artificial liver support systems.
AB  - Despite recent advances in medical therapy, patients with fulminant hepatic
      failure (FHF) have a mortality rate approaching 90%. Many patients die because of
      failure to arrest the progression of cerebral edema. Liver transplantation has
      improved survival to 65% to 75%. However, there is a shortage of donors and
      approximately one half of the patients with FHF will die while awaiting liver
      transplantation. There is thus a need to develop an extracorporeal liver assist
      system to help keep these patients alive and neurologically intact until either
      an organ becomes available for transplantation or the native liver recovers from
      injury. Such a system could also be used during the period of functional recovery
      from massive liver resection or to assist patients with decompensated chronic
      liver disease. Over the years, various methods utilizing charcoal and resin
      hemoperfusion, dialysis, plasma exchange, and other methods of blood
      detoxification have been developed and tested, but none have gained wide
      acceptance. This was due to: (i) incomplete understanding of the pathophysiology
      of liver failure; (ii) lack of accurate methods of assessment, quantitation, and
      stratification of the degree of liver dysfunction; and (iii) inadequate numbers
      of prospective controlled clinical trials examining the effects of specific
      therapeutic modalities. Liver support systems utilizing liver tissue preparations
      were developed in the 1950s, but it was not until recently that advances in
      hepatocyte isolation and culture, better understanding of hepatocyte-matrix
      interactions, and improved hollow-fiber technology have resulted in the
      development of a new generation of liver assist devices. Some of these devices
      are currently being tested in the clinical setting. In a preliminary clinical
      study, we have used a porcine hepatocyte-based liver support system to treat
      patients with acute liver failure as well as patients with acute exacerbation of
      chronic liver disease. Patients in the first group, who were candidates for
      transplantation, were successfully bridged to a transplant with excellent
      survival. No obvious benefit from bioartifical liver treatments was seen in the
      second group. It is possible that, in this group, patients will have to be
      treated earlier and for longer periods of time. Prospective controlled trials
      will be initiated as soon as the current phase I study is concluded to determine
      the efficacy of this system in both patients populations. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18626988
TI  - Motility behavior of hepatocytes on extracellular matrix substrata during
      aggregation.
AB  - Aggregation of hepatocytes in culture is an important phenomenon to control in
      tissue engineering applications. Aggregation generally enhances maintenance of
      differentiated functions but inhibits cell growth. At present there exists
      insufficient information for rational design of substrata that control
      aggregation. Indeed, the cellular mechanism(s) underlying the aggregation process
      is poorly understood, although cell motility is generally considered to be an
      essential phenomenon. In this article we provide the first study investigating
      the relationship between hepatocyte aggregation and motility behavior on various
      extracellular matrix substrata, including Matrigel, laminin, and fibronectin. We
      find that the extent of aggregation depends on the concentration of the
      extracellular matrix proteins, as well as on the type. Furthermore, we find that
      the extent of aggregation appears to be independent of classical single-cell
      locomotion. In fact, under conditions giving rise to substantial aggregation, the
      fraction of cells exhibiting classical locomotion is essentially negligible.
      Instead, aggregation appears to involve intracellular contacts accomplished via a
      different form of cell motility: active cell membrane extensions followed by
      adhesive cell-cell interactions. An implication of these findings is that
      aggregation may be largely governed by relative strengths of cell-cell versus
      cell-substratum interactions. These observations could be helpful for improved
      design of cell transplantation devices and cell culture substrata. (c) 1996 by
      John Wiley & Sons, Inc.

PMID- 18626989
TI  - Efficient assembly of rat hepatocyte spheroids for tissue engineering
      applications.
AB  - Freshly harvested primary rat hepatocytes cultivated as multicellular aggregates,
      or spheroids, have been observed to exhibit enhanced liver-specific function and
      differentiated morphology compared to cells cultured as monolayers. An efficient
      method of forming spheroids in spinner vessels is described. Within 24 h after
      inoculation, greater than 80% of inoculated cells formed spheroids. This
      efficiency was significantly greater than that reported previously for formation
      in stationary petri dishes. With a high specific oxygen uptake rate of 2.0 x 10(
      9) mmol O(2)/cell/h, the oxygen supply is critical and should be monitored for
      successful formation. Throughout a 6-day culture period, spheroids assembled in
      spinner cultures maintained a high viability and produced albumin and urea at
      constant rates. Transmission electron microscopy indicated extensive cell-cell
      contacts and tight junctions between cells within spheroids. Microvilli-lined
      bile canaliculus-like channels were observed in the interior of spheroids and
      appeared to access the exterior through pores at the outer surface. Spheroids
      from spinner cultures exhibited at least the level of liver-specific activity as
      well as similar morphology and ultrastructure compared to spheroids formed in
      stationary petri dishes. Hepatocytes cultured as spheroids are potentially useful
      three-dimensional cell systems for application in a bioartificial liver device
      and for studying xenobiotic drug metabolism. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626990
TI  - Improvement of serum amino acid profile in hepatic failure with the bioartificial
      liver using multicellular hepatocyte spheroids.
AB  - We designed a bioartificial liver support system in which encapsulated
      multicellular spheroids of rat hepatocytes were utilized as a bioreactor in a
      hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene
      dish that contained hormonally defined medium, were encapsulated into
      microdroplets of agarose that contained about 9 x 10(7) rat hepatocytes. The
      medium, including 150 mL reservoir volume, was circulated in a closed circuit in
      which the cartridge was inserted. The pH and levels of dissolved oxygen were
      monitored and automatically regulated so that they were maintained within a
      constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0
      mg/L/h in this system. When the bioreactor cells in the system were replaced with
      Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate
      of 0.15 mg/L/h. The spheroids of primary culture hepatocytes had 13 times higher
      albumin-producing capacity than the aggregates of Hep G2. The serum of a patient
      with fulminant hepatic failure was circulated in this system with the spheroids
      of primary culture hepatocytes. The concentration of branched amino acid (BCAA)
      in the circuit significantly increased during the 48 h circulation, while the
      concentration of aromatic amino acid (AAA) and methionine decreased. The ratio of
      BCAA/AAA increased from 0.640 to 0.772, indicating that the hepatocyte spheroids
      had improved the imbalance of the amino acid profile in the serum. These findings
      indicate that this system may be a useful model for an artificial liver support.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18626991
TI  - Localized delivery of epidermal growth factor improves the survival of
      transplanted hepatocytes.
AB  - Hepatocyte transplantation may provide a new approach for treating a variety of
      liver diseases if a sufficient number of the transplanted cells survive over an
      extended time period. In this report, we describe a technique to deliver growth
      factors to transplanted hepatocytes to improve their engraftment. Epidermal
      growth factor (EGF) was incorporated (0.11%) into microspheres (19 +/- 12 mum)
      fabricated from a copolymer of lactic and glycolic acid using a double emulsion
      technique. The incorporated EGF was steadily released over 1 month in vitro, and
      it remained biologically active, as determined by its ability to stimulate DNA
      synthesis, cell division, and long-term survival of cultured hepatocytes. EGF
      containing microspheres were mixed with a suspension of hepatocytes, seeded onto
      porous sponges, and implanted into the mesentery of two groups of Lewis rats. The
      first group of animals had their portal vein shunted to the inferior vena cava
      prior to cell transplantation (portal-caval shunt = PCS), and the second group of
      animals did not (non-PCS). This surgical procedure improves the survival of
      transplanted hepatocytes. The engraftment of transplanted hepatocytes in PCS
      animals was increased two-fold by adding EGF microspheres, as compared to adding
      control microspheres that contained no growth factors. Devices implanted into non
      PCS animals had fewer engrafted hepatocytes than devices implanted into PCS
      animals, regardless of whether blank or EGF-containing microspheres were added.
      These results first indicate that it is possible to design systems which can
      alter the microenvironment of transplanted hepatocytes to improve their
      engraftment. They also suggest that hepatocyte engraftment is not improved by
      providing single growth factors unless the correct environment (PCS) is provided
      for the transplanted cells. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626992
TI  - Mini-review: Mechanical factors affecting cartilage regeneration in vitro.
AB  - In the last 5 to 10 years, tissue engineering has revolutionized the way in which
      medical researchers and clinicians are thinking of and, in some cases, actually
      treating diseases involving tissue damage and destruction. One such disease,
      osteoarthritis, results from progressive degeneration of articular cartilage,
      which has a limited ability to repair itself. With tissue engineering, scientists
      are now able to regenerate cartilage in vitro from isolated mature chondrocytes.
      While the regeneration process is still not fully understood, enough has been
      learned that physicians are already implanting cultured chondrocytes into humans
      and other animals in the hopes of effecting joint repair. One aspect which has
      not been fully explored is the effect of mechanical stress on developing and
      implanted cartilage, especially over the long term. This article will review in
      brief what is now known about the mechanical factors affecting cartilage
      regeneration in vitro and what still remains to be determined for optimum tissue
      engineering of cartilage constructs. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626993
TI  - Mini-review: Proactive biomaterials and bone tissue engineering.
AB  - Recent advances in cell isolation and culture procedures, combined with growing
      understanding and use of molecular biology and biochemistry techniques, have
      resulted in the establishment of a new field of biological/biomedical research:
      cellular and tissue engineering. In the biomaterials field, cell and tissue
      bioengineers are investigating the development of proactive biomaterials (for
      example, bioceramics, chemically modified implant metals, and biodegradable
      tissue scaffolds) which utilize cellular- or molecular-level methods of
      manipulating cell/tissue behavior in order to encourage clinically desirable
      biological events at the tissue-implant interface. In vitro investigations
      utilizing osteoblasts, osteoclasts, and appropriate precursor cells, combined
      with long-term (i.e., years) tissue engineering studies in vivo are needed to
      enhance current understanding of the many mechanisms involved in bone formation
      and regulation. Such understanding will allow the development of proactive
      biomaterials for use in bone, which can elicit specific, timely, and clinically
      desirable responses from surrounding cells and tissues. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18626994
TI  - Osteoblast migration on poly(alpha-hydroxy esters).
AB  - We investigated the migration of rat calvaria osteoblast populations on
      poly(alpha-hydroxy ester) films for up to 14 days to determine effects of
      substrate composition and culture conditions on the migratory characteristics of
      osteoblasts. Initial osteoblast culture conditions included cell colonies formed
      by seeding a high (84,000 cells/cm(2)) or low (42,000 cells/cm(2)) density of
      isolated osteoblasts on the polymer films, and bone tissue cultures formed by
      plating bone chips directly on the substrates. High density osteoblast colonies
      cultured and allowed to migrate and proliferate radially on 85:15 poly(DL-lactic
      co-glycolic acid) (PLGA) films, 75:25 PLGA films, and tissue culture polystyrene
      controls demonstrated that the copolymer ratio in the polymer films did not
      affect the rate of increase in substrate surface area (or culture area) covered
      by the growing cell colony. However, the rate of increase in culture area was
      dependent on the initial osteoblast seeding density. Initial cell colonies formed
      with a lower osteoblast seeding density on 75:25 PLGA resulted in a lower rate of
      increase in culture area, specifically 4.9 +/- 0.3 mm(2)/day, versus 14.1 +/- 0.7
      mm(2)/day for colonies seeded with a higher density of cells on the same polymer
      films. The proliferation rate for osteoblasts in the high and low density seeded
      osteoblast colonies did not differ, whereas the proliferation rate for the
      osteoblasts arising from the bone chips was lower than either of these isolated
      cell colonies. Confocal and light microscopy revealed that the osteoblast
      migration occurred as a monolayer of individual osteoblasts and not a calcified
      tissue front. These results demonstrated that cell seeding conditions strongly
      affect the rates of osteoblast migration and proliferation on biodegradable
      poly(alpha-hydroxy esters). (c) 1996 John Wiley & Sons, Inc.

PMID- 18626995
TI  - Stochastic dynamics of the nerve growth cone and its microtubules during neurite
      outgrowth.
AB  - The controlled extension of neurites is essential not only for nervous system
      development, but also for effective nerve regeneration after injury. This process
      is critically dependent on microtubule assembly since axons fail to elongate in
      the presence of drugs which disrupt normal assembly dynamics. For this reason,
      neurite outgrowth is potentially controllable by manipulation of the assembly
      state of the intracellular array of microtubules. Therefore, understanding how
      microtubule assembly dynamics and neurite outgrowth are coupled, in the absence
      of drugs, can lend valuable insight into the control and guidance of the
      outgrowth process. In the present study we characterized the stochastic dynamics
      of neurite outgrowth and its corresponding microtubule array, which advances
      concomitantly with the advance of the nerve growth cone, the highly motile
      structure at the terminus of the growing neurite, using reported fluorescent
      microscopic image sequences (Tanaka and Kirschner, 1991, J. Cell Biol. 115:345
      363). Although previously modeled as an uncorrelated random walk, the stochastic
      advance of the growth cone was found to be anticorrelated over a time scale of
      approximately 4 min, meaning that growth cone advances tended to be followed by
      growth cone retractions approximately 4 min later. The observed anticorrelation
      most likely reflects the periodic stops and starts of neurite outgrowth that have
      been reported anecdotally. A strikingly similar pattern of anticorrelation was
      also identified in the advance of the growth cone's microtubule array. Cross
      correlation analysis showed that growth cone dynamics tended to precede
      microtubule dynamics on a time scale of approximately 0-2 min, while microtubules
      tended to precede growth cone dynamics on a approximately 0-20-s time scale,
      indicating a close temporal coupling between microtubule and growth cone
      dynamics. Finally, the scaling of the mean-squared displacements with time for
      both the growth cone and microtubules suggested a fractional Brownian motion
      model which accounts for the observed anticorrelation of growth cone and
      microtubule advance. (c) 1996 John Wiley & Sons, Inc.

PMID- 18626996
TI  - Development of an in vivo gene mutation assay using the endogenous Pig-A gene:
      II. Selection of Pig-A mutant rat spleen T-cells with proaerolysin and sequencing
      Pig-A cDNA from the mutants.
AB  - We previously reported that rat spleen T-cells and peripheral red blood cells
      that are deficient in glycosylphosphatidylinositol (GPI) synthesis [presumed
      mutants for the phosphatidylinositol glycan complementation group A gene (Pig-A)]
      could be detected by flow cytometry (FCM) as cells negative for GPI-linked
      markers (CD48 and CD59, respectively). To establish this procedure as a rapid in
      vivo gene mutation assay, we have examined the Pig-A gene of GPI-deficient rat
      spleen T-cells for DNA sequence alterations. Splenocytes were isolated from male
      F344 rats, primed with ionomycin and phorbol-12-myristate-13-acetate, and seeded
      at limiting-dilution into 96-well plates. To select for GPI-deficient T-cells,
      the cells were cultured for 10 days in a medium containing rat T-STIM and 2 nM
      proaerolysin (ProAER). The frequency of ProAER-resistant (ProAER(r)) spleen T
      cells from control rats ranged from 1.3 x 10(-6) to 4.8 x 10(-6), while
      administration of three doses of 40 mg/kg N-ethyl-N-nitrosourea increased the
      frequency of ProAER(r) T-cells 100-fold at 4 weeks after dosing. FCM analysis of
      the cells in ProAER(r) clones revealed that they were CD48-negative, and thus
      presumably GPI-deficient. Sequencing of Pig-A cDNA from six ProAER(r) clones
      indicated that they all contained alterations in the Pig-A protein coding
      sequence; five had base pair substitutions and one had multiple exons deleted.
      These results indicate that GPI-deficient spleen T-cells are Pig-A gene mutants
      and support the use of FCM analysis of GPI-deficient cells as a rapid assay for
      measuring in vivo gene mutation.

PMID- 18626997
TI  - Comparison of metabolite profiles generated in Aroclor-induced rat liver and
      human liver subcellular fractions: considerations for in vitro genotoxicity
      hazard assessment.
AB  - Because it is well known that metabolites of chemicals and drugs are frequently
      the ultimate species responsible for genotoxicity and carcinogenicity, in vitro
      testing to identify the human genotoxicity hazard potential of new chemicals and
      drugs routinely utilizes liver S-9 fraction from rats treated with Aroclor 1254
      as a system that can generate metabolites. However, it is frequently questioned
      as to whether such an in vitro metabolite generation system is the most relevant
      for human risk, or whether the assay would be better served by using a human
      derived in vitro system. To address this, 16 common drugs have been examined for
      profiles of metabolites in Aroclor-induced rat liver S-9 and pooled human liver S
      9. Metabolite profiles were compared using high pressure liquid chromatography
      coupled with ion trap mass spectrometry, in line with ultraviolet or radiometric
      detection to help make semiquantitative comparisons. Results showed that, with
      few exceptions, metabolites generated in the human system were also generated in
      the rat system. Also, in several cases the rat system generated considerably more
      metabolites, suggesting that there is a potential that positive genotoxicity
      findings could be caused by metabolites that have no relevance to humans. These
      findings suggest that when conducting in vitro genotoxicity testing using the
      Aroclor-induced rat liver S-9 system, knowledge of the metabolite profile in the
      system is important, and a comparison to the profile generated in human liver S-9
      could be of value when interpreting the genotoxicity results.

PMID- 18626998
TI  - Faulty spindle checkpoint and cohesion protein activities predispose oocytes to
      premature chromosome separation and aneuploidy.
AB  - Aneuploidy accounts for a major proportion of human reproductive failures, mental
      and physical anomalies, and neoplasms. To heighten our understanding of normal
      and abnormal chromosome segregation, additional information is needed about the
      underlying molecular mechanisms of chromosome segregation. Although many
      hypotheses have been proposed for the etiology of human aneuploidy, there has not
      been general acceptance of any specific hypothesis. Moreover, it is important to
      recognize that many potential mechanisms exist whereby chromosome missegregation
      may occur. One area for investigating aneuploidy centers on the biochemical
      changes that take place during oocyte maturation. In this regard, recent results
      have shown that faulty mRNA of spindle-assembly checkpoint proteins and
      chromosome cohesion proteins may lead to aneuploidy. Also, postovulatory and in
      vitro aging of mouse oocytes has been shown to lead to decreased levels of Mad2
      transcripts and elevated frequencies of premature centromere separation. The
      intent of this review is to highlight the major events surrounding chromosome
      segregation and to present the published results that support the premise that
      faulty chromosome cohesion proteins and spindle checkpoint proteins compromise
      accurate chromosome segregation.

PMID- 18626999
TI  - Development of an in vivo gene mutation assay using the endogenous Pig-A gene: I.
      Flow cytometric detection of CD59-negative peripheral red blood cells and CD48
      negative spleen T-cells from the rat.
AB  - The product of the phosphatidylinositol glycan complementation group A gene (Pig
      A) is involved in the synthesis of glycosylphosphatidylinositol (GPI) anchors
      that link various protein markers to the surface of several types of mammalian
      cells, including hematopoietic cells. Previous observations indicate that Pig-A
      mutation results in the lack of GPI synthesis and the absence of GPI-anchored
      proteins on the cell surface. As a first step in designing a rapid assay for
      measuring Pig-A mutation in the rat, we developed flow cytometry (FCM) strategies
      for detecting GPI-negative cells in rat peripheral blood and spleen. Anti-CD59
      was used to detect GPI-anchored proteins on red blood cells (RBCs), and anti-CD48
      was used to detect GPI-anchored proteins on spleen T-cells. The spontaneous
      frequency of CD59-negative RBCs in five male F344 rats ranged from 1 x 10(-6) to
      27 x 10(-6). In contrast, treatment of five rats with three doses of 40 mg/kg N
      ethyl-N-nitrosourea (ENU) increased the frequency of CD59-negative RBCs to 183 x
      10(-6) to 249 x 10(-6) at 2 weeks and to 329 x 10(-6) to 413 x 10(-6) at 4 weeks
      after dosing. In the same 4-week posttreatment rats, the frequency of CD48
      negative T-cells was 11 x 10(-6) to 16 x 10(-6) in control rats and 194 x 10(-6)
      to 473 x 10(-6) in ENU-treated rats. The frequencies of GPI-deficient cells were
      similar for RBCs and spleen T-cells. These results indicate that FCM detection of
      GPI-linked markers may form the basis for a rapid in vivo mutation assay.
      Although RBCs may be useful for a minimally invasive assay, T-cells are a
      promising tissue for both detecting GPI-deficient cells and confirming that Pig-A
      gene mutation is the cause of the phenotype.

PMID- 18627000
TI  - Influence of DNA repair gene polymorphisms on the initial repair of MMS-induced
      DNA damage in human lymphocytes as measured by the alkaline comet assay.
AB  - We have applied the alkaline comet assay to study the functional impact of gene
      polymorphisms in base excision repair (APEX1 Asp148Glu, XRCC1 Arg194Trp, XRCC1
      Arg399Gln) and homologous recombination repair (XRCC3 Thr241Met, NBS1 Glu185Gln),
      two pathways that play crucial roles in the repair of DNA damage induced by
      methylmethane sulphonate (MMS). We also examined the effect of polymorphisms in
      mismatch repair (MLH1 -93 A/G) and nucleotide excision repair (XPD Lys751Gln) as
      putative negative controls based on the limited roles of these pathways in MMS
      induced repair. Phytohemagglutinin-stimulated peripheral lymphocytes from 52
      healthy individuals were treated with MMS and allowed to repair for 0, 15, 40, or
      120 min after a 6-min washing step. DNA damage was measured as a pseudo
      percentage score (comparable to % tail DNA) converted from a total visual score
      calculated from the distribution of cells with different degrees of damage
      (normal, mild, moderate and severe). The repair was faster at the beginning of
      the observation period than towards the end, and was not complete after 2 hr.
      Presence of the APEX1 148Asp, XRCC3 241Met or NBS1 185Gln alleles were
      significantly associated with a high pseudo-percentage score (above median) at
      early time points, with the APEX1 effect being most prolonged (up to 40 min after
      washing, odds ratio 5.6, 95% confidence interval 2.0-15.5). No significant
      effects were seen with the XRCC1 Arg194Trp, XRCC1 Arg399Gln, MLH1 -93A/G and XPD
      Lys751Gln polymorphisms. Our results provide evidence for the functional nature
      of the variant alleles studied in the APEX1, XRCC3, and NBS1 genes.

PMID- 18627001
TI  - Nocturnal nutritional supplementation improves total body protein status of
      patients with liver cirrhosis: a randomized 12-month trial.
AB  - Patients with liver cirrhosis exhibit early onset of gluconeogenesis after short
      term fasting. This accelerated metabolic reaction to starvation may underlie
      their increased protein requirements and muscle depletion. A randomized
      controlled trial was conducted to test the hypothesis that provision of a late
      evening nutritional supplement over a 12-month period would improve body protein
      stores in patients with cirrhosis. A total of 103 patients (68 male, 35 female;
      median age 51, range 28-74; Child-Pugh grading: 52A, 31B, 20C) were randomized to
      receive either daytime (between 0900 and 1900 hours) or nighttime (between 2100
      and 0700 hours) supplementary nutrition (710 kcal/day). Primary etiology of liver
      disease was chronic viral hepatitis (67), alcohol (15), cholestatic (6), and
      other (15). Total body protein (TBP) was measured by neutron activation analysis
      at baseline, 3, 6, and 12 months. Total daily energy and protein intakes were
      assessed at baseline and at 3 months by comprehensive dietary recall. As a
      percentage of values predicted when well, TBP at baseline was similar for the
      daytime (85 +/- 2[standard error of the mean]%) and nighttime (84 +/- 2%) groups.
      For the nighttime group, significant increases in TBP were measured at 3 (0.38 +/
      0.10 kg, P = 0.0004), 6 (0.48 +/- 0.13 kg, P = 0.0007), and 12 months (0.53 +/-
      0.17 kg, P = 0.003) compared to baseline. For the daytime group, no significant
      changes in TBP were seen. Daily energy and protein intakes at 3 months were
      higher than at baseline in both groups (P < 0.0001), and these changes did not
      differ between the groups. CONCLUSION: Provision of a nighttime feed to patients
      with cirrhosis results in body protein accretion equivalent to about 2 kg of lean
      tissue sustained over 12 months. This improved nutritional status may have
      important implications for the clinical course of these patients.

PMID- 18627002
TI  - Fertilization in vitro with spermatozoa from different mice increased variation
      in the developmental potential of embryos compared to artificial parthenogenetic
      activation.
AB  - Although successful embryo development is dependent upon genetic and epigenetic
      contributions from both the male and female, the male potential to adversely
      affect embryo development has been scarcely studied. It is unclear whether the
      sperm variation among different males would affect the outcome of oocyte
      evaluation by embryo development following fertilization. In the present study,
      variation in the developmental potential of mouse embryos was first compared
      between in vitro fertilization with epididymal spermatozoa from different males
      and Sr(2+) parthenogenetic activation using oocytes of different qualities, and
      then the effect of male on fertilization and embryo development was examined
      using randomly chosen oocytes and spermatozoa from cauda epididymidis, vas
      deferens or electro-ejaculates. Rates of fertilization and blastocyst formation
      were significantly higher with spermatozoa from cauda epididymidis or vas
      deferens than with ejaculated spermatozoa. Rates of embryonic development
      differed significantly between different males, but not between different
      ejaculates of the same male. Analysis of standard errors of means and
      coefficients of variance indicated that as long as multiple males were involved,
      the variation in oocyte fertilization/activation and blastocyst formation was
      always higher after fertilization than after Sr(2+) parthenogenetic activation
      whether spermatozoa were collected from epididymidis, vas deferens or ejaculates
      and regardless of oocyte qualities. It is concluded that (1) epididymal mouse
      spermatozoa fertilize more oocytes than ejaculated spermatozoa under identical
      experimental conditions; (2) like farm animals, the mice also show a remarkable
      male effect on the developmental potential of in vitro produced embryos although
      they are supposed to be less genetically diverse; (3) parthenogenetic activation
      is recommended for assessment of oocyte quality to exclude the effect of male.

PMID- 18627003
TI  - Visceral fat: a key mediator of steatohepatitis in metabolic liver disease.
AB  - Visceral obesity is intimately associated with metabolic disease and adverse
      health outcomes. However, a direct association between increasing amounts of
      visceral fat and end-organ inflammation and scarring has not been demonstrated.
      We examined the association between visceral fat and liver inflammation in
      patients with nonalcoholic fatty liver disease (NAFLD) to delineate the
      importance of visceral fat to progressive steatohepatitis and hence the
      inflammatory pathogenesis of the metabolic syndrome. We undertook a cross
      sectional, proof of concept study in 38 consecutive adults with NAFLD at a
      tertiary liver clinic. All subjects had a complete physical examination,
      anthropometric assessment, and fasting blood tests on the day of liver biopsy.
      Abdominal fat volumes were assessed by magnetic resonance imaging within 2 weeks
      of liver biopsy. The extent of hepatic inflammation and fibrosis augmented
      incrementally with increases in visceral fat (P < 0.01). For each 1% increase in
      visceral fat, the odds ratio for increasing liver inflammation and fibrosis was
      2.4 (confidence interval [CI]: 1.3-4.2) and 3.5 (CI: 1.7-7.1), respectively.
      Visceral fat remained an independent predictor of advanced steatohepatitis (odds
      ratio [OR] 2.1, CI: 1.1-4.2, P = 0.05) and fibrosis (OR 2.9, CI: 1.4-6.3, P =
      0.006) even when controlled for insulin resistance and hepatic steatosis.
      Interleukin-6 (IL-6) levels, which correlated with visceral fat, also
      independently predicted increasing liver inflammation. Visceral fat was
      associated with all components of the metabolic syndrome. CONCLUSION: Visceral
      fat is directly associated with liver inflammation and fibrosis independent of
      insulin resistance and hepatic steatosis. Visceral fat should therefore be a
      central target for future interventions in nonalcoholic steatohepatitis and
      indeed all metabolic disease.

PMID- 18627004
TI  - Multidrug resistance-associated proteins are crucial for the viability of
      activated rat hepatic stellate cells.
AB  - Hepatic stellate cells (HSCs) survive and proliferate in the chronically injured
      liver. ATP-binding cassette (ABC) transporters play a crucial role in cell
      viability by transporting toxic metabolites or xenobiotics out of the cell. ABC
      transporter expression in HSCs and its relevance to cell viability and/or
      activation have not been reported so far. The aim of this study was to
      investigate the expression, regulation, and function of multidrug resistance
      associated protein (Mrp)-type and multidrug resistance protein (Mdr)-type ABC
      transporters in activated rat HSCs. Rat HSCs were exposed to cytokines or
      oxidative stress. ABC transporter expression was determined by quantitative
      polymerase chain reaction and immunohistochemistry. HSCs were exposed to the Mdr
      inhibitors verapamil and PSC-833 and the Mrp inhibitor MK571. Mdr and Mrp
      transporter function was evaluated with flow cytometry. Apoptosis was determined
      by activated caspase-3 and acridine orange staining, and necrosis was determined
      by Sytox green nuclear staining. An in vivo model of carbon tetrachloride
      (CCl(4))-induced liver fibrosis was used. With respect to hepatocytes, activated
      HSCs expressed high levels of Mrp1 and comparable levels of Mrp3, Mrp4, Mdr1a,
      and Mdr1b but not the hepatocyte-specific transporters bile salt export pump,
      Mrp2, and Mrp6. Mrp1 protein staining correlated with desmin staining in livers
      from CCl(4)-treated rats. Mrp1 expression increased upon activation of HSCs.
      Cytokines induced Mdr1b expression only. Oxidative stress was not a major
      regulator of Mdr and Mrp transporter expression. Activated HSCs became necrotic
      when exposed to the Mrp inhibitors. CONCLUSION: Activated HSCs contain relatively
      high levels of Mrp1. Mrp-type transporters are required for the viability of
      activated HSCs. Mrp-dependent export of endogenous metabolites is important for
      the survival of activated HSCs in chronic liver diseases.

PMID- 18627005
TI  - Peroxisome proliferator-activated receptor-delta induces insulin-induced gene-1
      and suppresses hepatic lipogenesis in obese diabetic mice.
AB  - Primary nonalcoholic fatty liver disease is one of the most common forms of
      chronic liver diseases and is associated with insulin-resistant states such as
      diabetes and obesity. Recent work has revealed potential implications of
      peroxisome proliferator-activated receptor-delta (PPARdelta) in lipid homeostasis
      and insulin resistance. In this study, we examined the effect of PPARdelta on
      sterol regulatory element-binding protein-1 (SREBP-1), a pivotal transcription
      factor controlling lipogenesis in hepatocytes. Treatment with GW0742, the
      PPARdelta agonist, or overexpression of PPARdelta markedly reduced intracellular
      lipid accumulation. GW0742 and PPARdelta overexpression in hepatocytes induced
      the expression of insulin-induced gene-1 (Insig-1), an endoplasmic reticulum
      protein braking SREBP activation, at both the mRNA and the protein levels.
      PPARdelta inhibited the proteolytic processing of SREBP-1 into the mature active
      form, thereby suppressing the expression of the lipogenic genes fatty acid
      synthase, stearyl CoA desaturase-1, and acetyl coenzyme A carboxylase. Our
      results revealed a direct binding of PPARdelta to a noncanonical peroxisome
      proliferator responsive element motif upstream of the transcription initiation
      site of human Insig-1. The disruption of this site diminished the induction of
      Insig-1, which suggested that Insig-1 is a direct PPARdelta target gene in
      hepatocytes. Knockdown of endogenous Insig-1 attenuated the suppressive effect of
      GW0742 on SREBP-1 and its target genes, indicating PPARdelta inhibited SREBP-1
      activation via induction of Insig-1. Furthermore, overexpression of PPARdelta by
      intravenous infection with the PPARdelta adenovirus induced the expression of
      Insig-1, suppressed SREBP-1 activation, and, consequently, ameliorated hepatic
      steatosis in obese db/db mice. CONCLUSION: Our study reveals a novel mechanism by
      which PPARdelta regulates lipogenesis, suggesting potential therapeutic
      applications of PPARdelta modulators in obesity and type 2 diabetes, as well as
      related steatotic liver diseases.

PMID- 18627008
TI  - Tissue engineering, bioartificial organs, and cell therapies: II.

PMID- 18627009
TI  - In vitro characterization of fetal hematopoietic stem cells: range and kinetics
      of cell production from individual stem cells.
AB  - We have developed methods for detailed characterization of the proliferation
      kinetics and lineage potential of single human hematopoietic progenitor cells in
      an in vitro culture system. Fetal bone marrow CD34(hi)/lin(-) cells were cultured
      at one cell per well in the presence of c-kit ligand (KL), interleukin (IL)-3, IL
      6, and leukemia inhibitory factor (LIF) on a murine stroma cell monolayer.
      Individual wells were scored for growth between 1 and 10 weeks of culture and
      analyzed by flow cytometry for lineage composition. A wide variation in time (1
      to 8 weeks) was observed before initial cell division, even in the presence of
      cytokines promoting cell division in primitive progenitors. Eleven percent of the
      plated cells eventually produced a confluent culture well of approximately 20,000
      progeny. Confluent wells were harvested and individually analyzed by flow
      cytometry for cell surface phenotype. Forty-eight percent of confluent wells
      contained primitive progenitors (CD34(+)lin(-)), 16% contained B-lymphoid cells
      (CD19(+) or CD10(+)), and 100% contained cells committed to the myelo-erythroid
      lineage (CD33(+)). CD34(+)/lin(-) cells from confluent wells were replated at one
      cell per well in secondary culture and the analysis repeated. One of 216 original
      single cells plated produced populations of B-lymphoid cells, myeloid cells, and
      primitive progenitors (CD34(+)/lin(-)) which persisted through two expansion
      cycles. We estimate that more than 36 million cells can be produced from a single
      cell under these culture conditions. A very small percentage of the CD34(hi)/lin(
      ) population (about 1%) was responsible for the majority of subsequent cell
      production. Our estimate of stem cell content in fetal bone marrow, defined by
      self-renewal as well as both B-lymphoid and myeloid differentiation from one
      cell, is approximately 1/13,000. This assay system provides direct in vitro
      measurements of the expected characteristics of hematopoietic stem cells (high
      proliferation potential, multilineage potential, self-renewal, and quiescence),
      and is therefore well suited to assessment of stem cell activity within various
      cell populations.

PMID- 18627006
TI  - Histone deacetylase 11 regulates oligodendrocyte-specific gene expression and
      cell development in OL-1 oligodendroglia cells.
AB  - Both in vivo and in vitro studies indicate a correlation between reduced
      acetylation of histone core proteins and oligodendrocyte development. The nature
      of these histone modifications and the mechanisms mediating them remain
      undefined. To address these issues, we utilized OL-1 cells, a rat nontransformed
      oligodendrocyte cell line, and primary oligodendrocyte cultures. We found that
      the acetylated histone H3 at lysine 9 and lysine 14 (H3K9/K14ac) is reduced in
      both the myelin basic protein (MBP) and proteolipid protein (PLP) genes of
      maturing oligodendroglial OL-1 cells, and furthermore, this temporally correlates
      with increases in MBP, PLP, and histone deacetylase (HDAC) 11 expression.
      Disruption of developmentally-regulated histone H3 deacetylation within the MBP
      and PLP genes by the HDAC inhibitor trichostatin A blunts MBP and PLP expression.
      With its increased expression, interaction of HDAC 11 with acetylated histone H3
      and recruitment of HDAC 11 to the MBP and PLP genes markedly increases in
      maturing OL-1 cells. Moreover, suppressing HDAC 11 expression with small
      interfering RNA significantly (1) increases H3K9/K14ac globally and within the
      MBP and PLP genes, (2) decreases MBP and PLP mRNA expression, and (3) blunts the
      morphological changes associated with oligodendrocyte development. Our data
      strongly support a specific role for HDAC 11 in histone deacetylation and in turn
      the regulation of oligodendrocyte-specific protein gene expression and
      oligodendrocyte development.

PMID- 18627010
TI  - Cell growth and differentiation on feeder layers is predicted to be influenced by
      bioreactor geometry.
AB  - Tissue function is comprised of a complex interplay between biological and
      physicochemical rate processes. The design of bioreactors for tissue engineering
      must account for these processes simultaneously in order to obtain a bioreactor
      that provides a uniform environment for tissue growth and development. In the
      present study we consider the effects of fluid flow and mass transfer on the
      growth of a tissue in a parallel-plate bioreactor configuration. The parenchymal
      cells grow on a preformed stromal (feeder) layer that secretes a growth factor
      that stimulates parenchymal stem cell replication and differentiation. The
      biological dynamics are described by a unilineage model that describes the
      replication and differentiation of the tissue stem cell. The physicochemical
      rates are described by the Navier-Stokes and convective-diffusion equations. The
      model equations are solved by a finite element method. Two dimensionless groups
      govern the behavior of the solution. One is the Graetz number (Gz) that describes
      the relative rates of convection and diffusion, and the other a new dimensionless
      ratio (designated by P) that describes the interplay of the growth factor
      production, diffusion, and stimulation. Four geometries (slab, gondola, diamond,
      and radial shapes) for the parallel-plate bioreactor are analyzed. The uniformity
      of cell growth is measured by a two-dimensional coefficient of variance. The
      concentration distribution of the stroma-derived growth factor was computed first
      based on fluid flow and bioreactor geometry. Then the concomitant cell density
      distribution was obtained by integrating the calculated growth factor
      concentration with the parenchymal cell growth and unilineage differentiation
      process. The spatiotemporal cell growth patterns in four different bioreactor
      configurations were investigated under a variety of combinations of Gz (10(-1),
      10(0), and 10(1)) and P(10(-2), 10(-1), 10(0), 10(1), and 10(2)). The results
      indicate high cell density and uniformity can be achieved for parameter values of
      P = 0.01, ..., 0.1 and Gz = 0.1, ..., 1.0. Among the four geometries investigated
      the radial-flow-type bioreactor provides the most uniform environment in which
      parenchymal cells can grow and differentiate ex vivo due to the absence of walls
      that are parallel to the flow paths creating slow flowing regions.

PMID- 18627011
TI  - Development of novel perfusion chamber to retain nonadherent cells and its use
      for comparison of human "mobilized" peripheral blood mononuclear cell cultures
      with and without irradiated bone marrow stroma.
AB  - Perfusion and static cultures of peripheral blood (PB) mononuclear cells (MNCs),
      obtained from patients following stem cell mobilization, were supplemented with
      interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor (G-CSF), and
      stem cell factor (SCF) and compared with and without a preformed irradiated
      allogeneic bone marrow stromal layer. Perfusion cultures without a stromal layer
      effectively retained nonadherent cells through the use of a novel "grooved"
      perfusion chamber, which was designed with minimal mass transfer barriers in
      order to achieve a well-defined culture environment. The grooved chamber allowed
      easy and efficient culture inoculation and cell recovery. Average maximum
      expansion of CFU-GM (colony-forming unit granulocyte-macrophage) cells was
      observed on day 10 for all cultures. Perfusion cultures had a maximum CFU-GM
      expansion of 17- and 19-fold with and without a stromal layer, respectively. In
      contrast, static cultures had a maximum CFU-GM expansion of 18- and 13-fold with
      and without a stromal layer, respectively. Average long-term-culture initiating
      cell (LTC-IC) numbers on day 15 were 34% and 64% of input in stroma-containing
      and stroma-free perfusion cultures and 12% and 11% of input in stroma-containing
      and stroma-free static cultures, respectively. Thus, perfusion enhanced CFU-GM
      expansion and LTC-IC maintenance more for the stroma-free cultures than for
      stroma-containing cultures. This was surprising because analysis of medium
      supernatants indicated that the stroma-containing cultures were metabolically
      more active than the stroma-free cultures. In view of their equivalent, if not
      superior, performance compared to stroma-containing cultures, stroma-free
      perfusion cultures may offer significant advantages for potential clinical
      applications.

PMID- 18627012
TI  - Different measures of human hematopoietic cell culture performance are optimized
      under vastly different conditions.
AB  - Hematopoiesis, the formation of mature blood cells from stem (LTC-IC) and
      progenitor (CFU-GM) cells in the bone marrow, is a complex tissue-forming process
      that leads to many important physiological functionalities. Consequently, a
      functioning ex vivo hematopoietic system has a variety of basic scientific and
      clinical uses. The design and operation of such a system presents the tissue
      engineer with challenges and choices. In this study, three culture variables were
      used to control ex vivo human hematopoiesis. Systematic variation of inoculum
      density (ID), medium exchange interval (MEI), and the use of preformed stroma
      (PFS) showed that (1) all three variables significantly influenced culture
      performance, (2) the three variables interacted strongly, and (3) the variables
      could be manipulated to achieve the optimization of different performance
      criteria. Donor-to-donor variability in culture performance was great at low ID
      but was minimized at higher ID. PFS had a large positive effect on cell and CFU
      GM output at low ID, but had minimal effect at higher ID. In fact, PFS caused a
      decrease in LTC-IC output at high ID. The effects of PFS indicated that stromal
      cell elements became more limiting than proliferative cell elements as ID was
      reduced.In cultures without PFS, maximum cell output was obtained with high ID
      using a short MEI, whereas the greatest cell expansion ratio was obtained at low
      ID with an intermediate MEI. Maximum CFU-GM output was obtained from cultures
      with high ID using a short to intermediate MEI, whereas the greatest CFU-GM
      expansion ratio was obtained at intermediate ID with an intermediate MEI. The
      addition of PFS altered the locations of these maxima. In general, PFS moved the
      maxima to lower ID, and culture output became more sensitive to MEI. Therefore,
      the optimization of one performance criterion always resulted in a decline of the
      others. This study demonstrates that ex vivo tissue function is sensitive to many
      culture variables in an interactive fashion and that systematic multivariable
      studies are required to characterize tissue function. Once the effects of
      individual variables and their interactions are known, this knowledge can be used
      to optimize tissue performance with respect to desired criteria.

PMID- 18627013
TI  - Large-scale production of murine bone marrow cells in an airlift packed bed
      bioreactor.
AB  - Large-scale cultivation of murine bone marrow cells was accomplished in an
      airlift packed bed bioreactor system designed to mimic the in vivo bone marrow
      environment. The attachment-dependent stromal cell population, which provides the
      necessary microenvironment, including growth factors for subsequent hematopoietic
      activity, was first established within the bioreactor. This attachment-dependent
      cell growth occurred on the fiber-glass matrix packed in the annular region of
      the bioreactor. Once the stromal cell layer was established, fresh bone marrow
      cells were inoculated to initiate hematopoiesis. However, traditional culture
      medium was found to be inadequate for the initiation of hematopoiesis, but the
      use of stromal cell "conditioned" medium (with no exogenously added growth
      factors) yielded sustained cell production. The extent of stromal cell
      subculturing prior to inoculation into the bioreactor and the inoculation density
      were also important factors for the successful initiation of hematopoietic
      activity. A 500-mL perfusion culture experiment resulted in the production and
      harvest of 3.6 x 10(8) suspended bone marrow cells over the course of 11 weeks.

PMID- 18627014
TI  - Serum enhances the ex vivo generation of HIV-specific cytotoxic T cells.
AB  - The ex vivo expansion of antigen-specific cytotoxic T lymphocyte (CTL) lines is
      being developed for immunotherapy of viral infections and cancer and is
      critically dependent on the precise cell expansion and stimulation conditions. In
      this article, we investigate medium requirements for the development of HIV
      specific CTL in cell lines generated from the peripheral blood of seven
      asymptomatic HIV-infected individuals. We find that HIV-specific CTL do not
      readily develop in the serum-free medium AIM V but do develop if the medium is
      supplemented with 1% plasma or serum. T cell lines with antigen-specific
      cytolytic activity express more cell-surface CD57 than do cell lines grown in the
      absence of serum or plasma. Three sources of serum (human autologous, human AB,
      or fetal calf) are comparable. Human plasma is somewhat less effective than serum
      from an identical source.

PMID- 18627015
TI  - Generation and ex vivo expansion of HTLV-1 specific CD8+ cytotoxic T-lymphocytes
      for adoptive immunotherapy.
AB  - CD8(+) cytotoxic T-lymphocytes (CTLs) have been proven, in multiple animal
      models, to be the most powerful antiviral and antitumor components of the immune
      system. We have developed a protocol to activate and expand tumor and virus
      peptide-specific CD8(+) T-lymphocytes from the peripheral blood of healthy, human
      trophic leukemia virus-1 (HTLV-1) seronegative human leucocyte antigen (HLA)
      A*0201 individuals. A combination of density-based separation and culture
      conditions was employed to isolate dendritic cells (DCs), which are the most
      potent antigen-presenting cells (APCs), and T-lymphocytes. The DCs were pulsed
      with HLA-A*0201 binding peptides and cultured with autologous T-lymphocytes to
      generate peptide-specific CTLs. The CTLs were generated against a nine-amino-acid
      peptide from the Tax protein of HTLV-1. The CTLs were expanded according to a
      restimulation schedule employing peptide-pulsed autologous monocytes and low-dose
      interleukin-2 (IL-2) to numbers in excess of 100 x 10(6) cells following 5 weeks
      of culture. Expanded cells contained primarily CD3(+) T-cells, of which CD8(+) T
      lymphocytes constituted greater than two-thirds of the cell population. Obtained
      CTLs exhibited potent antigen-specific lysis of peptide-pulsed target cells in a
      dose-dependent fashion in in vitro (51)Cr release cytotoxicity assay. This
      antigen-specific killing was shown to be HLA class I restricted and mediated by
      CD8(+) T-lymphocytes. Since the T-lymphocytes were obtained from HTLV-1
      seronegative donors, the generation of peptide-specific CTLs represents reliable
      and reproducible elicitation of a primary immune response in vitro against naive
      antigens and subsequent expansion of generated CTLs for adoptive immunotherapy.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18627016
TI  - Validation of an automated method of endotoxin testing for use in the end-product
      testing of ex vivo activated T-lymphocytes used in a somatic cell therapy.
AB  - The aim of this study was to compare two methods of endotoxin testing to optimize
      quality control testing methodologies required for the rapid and precise
      determination of pyrogenicity in cell or tissue products used in cellular
      therapies. An automated kinetic-chromogenic method for determination of endotoxin
      levels in ex vivo activated T-lymphocytes infusion product, has been validated
      following the FDA guideline for the Limulus amebocyte lysate (LAL) assay. The
      validation protocol included: (1) initial qualification of the laboratory
      conducting the assay; (2) inhibition and enhancement tests both for treated
      (heated at 70 degrees C for 10 min) and untreated specimens; and (3) comparison
      of this assay with the conventional gel-clot method. Inhibition and enhancement
      testing showed that a 1:30 dilution of the infusion product was the optimal
      dilution for this type of specimen. Heating specimens did not appear to provide
      any advantage. A comparison study was performed on 105 infusion product samples.
      Endotoxin levels determined by both methods for all samples tested were within
      established end-product release specifications. The K-QCL method can be
      effectively used for endotoxin determination of ex vivo activated T-cells.

PMID- 18627017
TI  - Cationic liposomal delivery of plasmid to endothelial cells measured by
      quantitative flow cytometry.
AB  - Cationic liposomes are potentially important gene transfer vehicles, capable of
      conjugating with anionic DNA by condensation. Flow cytometry was used to examine
      quantitatively the incorporation of DNA-liposome complex into murine capillary
      lung endothelial cells. The plasmid DNA, a pSV-beta-galactosidase vector, was
      covalently labeled with ethidium monoazide by photoactivation. The cationic
      liposome consisted of egg phosphatidylcholine (90%), cholesterol (5%), and
      stearylamine (5%). The number of plasmid molecules contained within each cell as
      a function of exposure time was estimated from fluorescence intensity.
      Fluorescently labeled plasmid is detectable after 10 min and increases with
      continued exposure, but at a decreasing rate, up to 2160 min. After 2160 min each
      cell, on average, contains approximately 10,000 plasmid molecules. Following
      transfection, a single cell unimodal population was detected by flow cytometry,
      suggesting that all cells participate in transfection equally. Furthermore, cell
      cycle analysis indicates that the entry of DNA-liposome complex is independent of
      cell cycle.

PMID- 18627018
TI  - Effects of shear stress on the growth kinetics of human aortic smooth muscle
      cells in vitro.
AB  - After cardiovascular intervention, smooth muscle cells (SMC) are directly exposed
      to blood flow and thus their behavior might be affected by fluid hemodynamic
      forces. The aim of this study was to determine the effect of fluid shear stress
      on the growth rate of SMC. Human aortic smooth muscle cells (hASMC) were seeded
      on fibronectin-coated glass slides and were exposed to different levels of shear
      stress using parallel plate flow chambers. After 24 h, cell numbers in the
      stationary and sheared cultures were measured by a Coulter counter. Results
      demonstrated that increasing shear stress significantly reduces the proliferation
      rate of hASMC (P < 0.05). Comparable lactate dehydrogenase levels in the media of
      stationary and flow cultures provided evidence that the reduction of cell number
      was not due to cell injury. Proliferating cell nuclear antigen (PCNA)
      immunofluorescence studies indicated that the cell cultures were not growth
      arrested 24 h after exposure to shear stress, and that the differences in PCNA
      staining between stationary control and flow cultures were comparable to the cell
      counts.

PMID- 18627019
TI  - Tissue engineering lamb heart valve leaflets.
AB  - Tissue engineered lamb heart valve leaflets (N - 3) were constructed by
      repeatedly seeding a concentrated suspension of autologous myofibroblasts onto a
      biodegradable synthetic polymeric scaffold composed of fibers made from
      polyglycolic acid and polylactic acid. Over a 2-week period the cells attached to
      the polymer fibers, multiplied, and formed a tissue core in the shape of the
      matrix. The tissue core was seeded with autologous large-vessel endothelial cells
      that formed a monolayer which coated the outer surface of the leaflet. The tissue
      engineered leaflets were surgically implanted in place of the right posterior
      pulmonary valve leaflet of the donor lamb while on cardiopulmonary bypass.
      Pulmonary valve function was evaluated by two-dimensional echocardiography with
      color Doppler which demonstrated valve function without evidence of stenosis and
      with only trivial regurgitation under normal physiologic conditions.
      Histologically, the tissue engineered heart valve leaflets resembled native valve
      leaflet tissue.

PMID- 18627020
TI  - Measurement of trans-epithelial electrical resistance in perfusion: potential
      application for in vitro ocular toxicity testing.
AB  - An in vitro toxicity testing system that combines perfusion of a membrane
      supported tissue model with measurement of trans-epithelial electrical resistance
      (TER) is described. The system is fully automated and allows for continuous TER
      measurements during exposure to a test agent. The utility of this system is
      demonstrated by the TER response of a tissue model composed of MDCK cells
      cultured on a cellulose ester filter to a series of nonionic surfactants (Triton
      X-100, Tween-20, Tween-80). The relative toxicities of the surfactants, as
      evaluated by the time needed to cause a 50% reduction in TER, are consistent with
      in vivo test results and with results from previous in vitro assays in static
      culture. The system can also be used to follow recovery of TER after a test agent
      has been removed from the perfusate. If the TER of the MDCK cell layer does not
      fall below a threshold value during surfactant exposure, the TER recovers at
      least part of the way to preexposure levels, beginning several hours after
      removal of the surfactant. A major benefit of this system is the increased amount
      of data obtained compared to traditional static assay systems. This may allow
      identification of parameters that correlate with different aspects of in vivo
      exposure.

PMID- 18627021
TI  - Effect of culture age on the susceptibility of differentiating neuroblastoma
      cells to retinoid cytotoxicity.
AB  - The cytotoxic effects of retinoids on neuroblastoma cells at various times during
      electrophysiological differentiation were evaluated. We used N1E-115, a clone of
      the murine neuroblastoma C1300 derived from the neural crest, and three
      retinoids: vitamin A (retinol), all-trans retinoic acid (tretinoin), and 13-cis
      retinoic acid (isotretinoin). Differentiating N1E-115 cells exposed to retinoids
      at an isotretinoin EC(50) of 16 microM exhibited the greatest vulnerability in
      terms of cell death during a period (8 to 10 days) that was previously found to
      be the most sensitive for induction of gross malformations in rodents. This
      finding suggested possible similarities between the in vivo and in vitro retinoid
      mechanism(s) of action. The greatest period of vulnerability to retinoid
      cytotoxicity was also found to coincide with the rapid resting membrane potential
      (V(m)) development period, suggesting a linkage between neuronal V(m) and/or
      electrical excitability development and vulnerability to retinoid cytotoxicity.

PMID- 18627022
TI  - Effects of simulated microgravity on DU 145 human prostate carcinoma cells.
AB  - The high aspect rotating-wall vessel (HARV) was recently designed by NASA to
      cultivate animal cells in an environment that simulates microgravity. This work
      examines the effects of HARV cultivation on DU 145 human prostate carcinoma
      cells. In the HARV, these prostate cells grew in suspension on Cytodex-3
      microcarrier beads to form bead aggregates with extensive three-dimensional
      growth between beads and on the aggregate surface. HARV and spinner-flask control
      cultures of DU 145 cells had similar doubling times, but the former was
      characterized by a higher percentage of G(1)-phase cells, larger bead aggregates,
      enhanced development of filopodia and microvilli-like structures on the aggregate
      surface, and stronger staining for select cytoskeletal proteins (cytokeratins 8
      and 18, actin, and vimentin). When compared with static controls grown in a T
      flask and Transwell insert, HARV cultures grew more slowly and differences in the
      cell cycle and immunostaining became more pronounced. These results suggest that
      HARV cultivation produced a culture that was less aggressive from the perspective
      of proliferation, more differentiated and less pliant than any of the three
      control cultures examined in this work. Possible factors effecting this change
      are discussed including turbulence and three-dimensional growth.

PMID- 18627023
TI  - Computerized analysis of tumor cell interactions with extracellular matrix
      proteins, peptides, and endothelial cells under laminar flow.
AB  - Arrest and formation of stable adhesive interactions between circulating cells
      and the endothelium or exposed subendothelial matrix are important processes in
      many biological situations. We have developed a highly sensitive hydrodynamic
      assay that utilizes a parallel-plate flow chamber, video microscopy, and digital
      image processing to separate and measure the primary arrest and adhesion
      stabilization of flowing cells. Our data indicate that primary cell contact
      triggers secondary adhesion stabilization, and the secondary events are likely to
      be critical to metastasis formation. To study the relationship between tumor cell
      adhesion stabilization and organ-specific blood-borne metastasis, we investigated
      the adhesion stabilization of metastatic murine RAW117 large-cell lymphoma cells
      to the extracellular matrix proteins fibronectin and vitronectin, several Arg-Gly
      Asp (RGD) containing peptides, and microvascular endothelial cells from the liver
      or lung. The highly liver metastatic RAW117-H10 subline showed the fastest
      stabilization to fibronectin, vitronectin, and RGD peptides. Poorly metastatic
      RAW117-P cells had stabilization times 3-10 times longer than for RAW117-H10
      cells, while the lung- and liver-metastatic RAW117-L17 subline failed to
      stabilize at all. The adhesion stabilization of the RAW117-H10 cells to the
      extracellular matrix proteins and RGD peptides was inhibited by anti-beta(3)
      integrin monoclonal antibodies and RGD peptides. In contrast, the RAW117-L17
      subline had the shortest stabilization time to unstimulated microvascular
      endothelial cells of the lung and hepatic sinusoids, followed by RAW117-H10 cells
      and RAW117-P cells. Monoclonal antibodies against the beta(3) integrin subunit
      and RGD peptides did not inhibit adhesion stabilization of RAW117-H10 cells to
      endothelial cells, suggesting that different metastatic variants of large-cell
      lymphoma cells use differing mechanisms to adhere to organ-specific endothelial
      cells.

PMID- 18627024
TI  - Recombinant arginine deiminase reduces inducible nitric oxide synthase iNOS
      mediated neurotoxicity in a coculture of neurons and microglia.
AB  - Modulation of nitric oxide (NO) production is considered a promising approach to
      therapy of diseases involving excessive inducible nitric oxide synthase (iNOS)
      expression, such as certain neuronal diseases. Recombinant arginine deiminase
      (rADI, EC3.5.3.6) catalyzes the conversion of L-arginine (L-arg), the sole
      substrate of NOS for NO production, to L-citrulline (L-cit) and ammonia. To
      understand the effect of the depletion of L-arg by rADI on NO concentration and
      neuroprotection, a direct coculture of neuron SHSY5Y cells and microglia BV2
      cells treated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was
      used as a model of iNOS induction. The results showed that rADI preserved cell
      viability (4-fold higher compared with the cells treated with LPS/IFN-gamma only)
      by the MTT assay, corresponding with the results of neuronal viability by neuron
      specific immunostaining assay. NO production (mean +/- SD) decreased from 67.0 +/
      1.3 to 19.5 +/- 5.5 microM after a 2-day treatment of rADI by the Griess assay;
      meanwhile, induction of iNOS protein expression by rADI was observed. In
      addition, rADI substantially preserved the neuronal function of dopamine uptake
      in the coculture. The replenishment of L-arg in the coculture eliminated the
      neuroprotective and NO-suppressive effects of rADI in the coculture, indicating
      that L-arg played a crucial role in the effects of rADI. These results highlight
      the important role of L-arg in the neuron-microglia coculture in excessive
      induction of iNOS. Regulation of L-arg by ADI demonstrated that rADI has a
      potentially therapeutic role in iNOS-related neuronal diseases.

PMID- 18627026
TI  - Light and food signals cooperate to entrain the rat pineal circadian system.
AB  - Light and food signals are two dominant Zeitgeber for central and peripheral
      circadian clocks, respectively. However, whether and how changes in light and
      food stimuli affect circadian rhythms of mammalian pineal clock genes are still
      largely unknown. For the first time, in the present study, we established a
      method for analysis of the expression levels of most clock genes (Bmal1, Per1,
      Per2, Per3, Cry1, Dec1 and Dec2) and AANAT in a single rat pineal gland and used
      it to investigate individual and cooperative effects of feeding and light cycle
      reversals on the pineal circadian system. Feeding reversal (RF) alone for 7 days
      had only weak effect on the rhythmicity of clock gene expression in the pineal
      gland, whereas light/dark reversal for the same period without any change in the
      feeding regime could not absolutely reverse the expression phases of all examined
      genes either. However, reversal of the LD cycle together with the feeding regime
      completely resynchronized the circadian gene expression in the pineal gland
      within 7 days. These data suggest that photic regulation is the dominant cue that
      synchronizes the pineal circadian rhythm more efficiently than the feeding
      related cue, but food availability does contribute to reentrainment of the pineal
      circadian system. In addition, the inability of RF in the pineal circadian system
      suggests that the pineal gland is more strongly coupled to the master clock than
      other peripheral organs and alternatively distinguishes it from other peripheral
      organs in the hierarchically organized mammalian circadian systems.

PMID- 18627025
TI  - Neurotrimin is an estrogen-regulated determinant of peripheral sympathetic
      innervation.
AB  - Mechanisms underlying axon degeneration in peripheral neuropathies and during
      normal remodeling are poorly understood. Because estrogen induces widespread
      sympathetic axon degeneration in female reproductive tract smooth muscle, we
      surveyed estrogen-regulated genes in rat myometrium. Microarray analysis revealed
      that the neural cell adhesion protein neurotrimin (Ntm) was markedly up-regulated
      6 hr and down-regulated 24 hr after injection of 17beta-estradiol, and real time
      RT-PCR confirmed this pattern of expression. Protein analysis by Western blotting
      showed that uterine Ntm protein is also up-regulated in vivo 6-24 hr following
      estrogen injection and that Ntm protein is increased selectively in the
      myometrium during the high-estrogen phase of the estrous cycle. Cultured
      myometrial smooth muscle cells display perinuclear accumulations of Ntm protein,
      and 17beta-estradiol also increases intracellular levels of Ntm and its secretion
      into the culture medium. To determine if neurotrimin is required for estrogen
      induced sympathetic pruning, sympathetic neurons were cocultured with uterine
      smooth muscle cells transfected with siRNA directed against Ntm. Although
      estrogen inhibited neurite outgrowth in nontransfected cocultures, estrogen's
      ability to reduce sympathetic outgrowth was impaired substantially following Ntm
      down-regulation. This supports a role for neurotrimin in mediating estrogen
      induced sympathetic pruning in some peripheral targets. Together with earlier
      studies, these findings support the idea that physiological sympathetic axon
      degeneration is a multifactorial process requiring dynamic regulation of multiple
      repellant proteins.

PMID- 18627027
TI  - Fibroblast growth factor-2 mRNA expression in the brainstem and spinal cord of
      normal and chronic spinally transected urodeles.
AB  - Descending pathways in the spinal cord of adult urodele amphibians show a high
      regenerative ability after body spinal cord transection; regenerated axons regrow
      into the transected spinal cord, and hindlimb locomotor recovery occurs
      spontaneously. Little is currently known about the molecular basis of spinal cord
      regeneration in urodeles, but it is believed that fibroblast growth factor-2
      (FGF2) may play an important role by inducing proliferation of neural progenitor
      cells. The aim of our study, using in situ hybridization in adult Pleurodeles
      waltlii, was twofold: 1) to document FGF2 mRNA expression pattern along the
      brainstem-spinal cord of intact salamanders and 2) to investigate the changes in
      this pattern in animals unable to display hindlimb locomotor movements and in
      animals having fully recovered hindlimb locomotor activity after body spinal cord
      transection. This design establishes a firm basis for further studies on the role
      of FGF2 in functional recovery of hindlimb locomotion. Our results revealed a
      decreasing rostrocaudal gradient in FGF2 mRNA expression along the brainstem
      spinal cord in intact animals. They further demonstrated a long-lasting up
      regulation of FGF2 mRNA expression in response to spinal transection at the
      midtrunk level, both in brainstem and in the spinal cord below the injury.
      Finally, double immunolabeling showed that FGF2 was up-regulated in neuroglial,
      presumably undifferentiated, cells. Therefore, we propose that FGF2 may be
      involved in cell proliferation and/or neuronal differentiation after body spinal
      cord transection in salamander and could thus play an important role in
      functional recovery of locomotion after spinal lesion.

PMID- 18627028
TI  - Involvement of independent mechanism upon poly(ADP-ribose) polymerase (PARP)
      activation in methylmercury cytotoxicity in rat cerebellar granule cell culture.
AB  - Poly(ADP-ribose) polymerase (PARP) activation plays a role in repairing injured
      DNA, while its overactivation is involved in various diseases, including neuronal
      degradation. In the present study, we investigated the use of a PARP inhibitor,
      3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), whether
      methylmercury-induced cell death in the primary culture of cerebellar granule
      cells involved PARP activation. DPQ decreased the methylmercury-induced cell
      death in a dose-dependent manner. Unexpectedly, this protective effect was DPQ
      specific; none of the other PARP inhibitors--1,5-dihydroxyisoquinoline, 3
      aminobenzamide, or PJ34--affected neuronal cell death. Methylmercury-induced cell
      death involves the decrease of glutathione (GSH) and production of reactive
      oxygen species. Therefore, to understand the mechanism by which DPQ inhibits
      cytotoxicity, we first studied the effect of DPQ on buthionine sulfoximine- or
      diethyl maleate-induced death of primary cultured cells and human neuroblastoma
      IMR-32 cells, both of which are mediated by GSH depletion. DPQ inhibited the cell
      death of both cultured cells, but it did not restore the decrease of cellular GSH
      by buthionine sulfoximine to the control level. Second, we evaluated the
      antioxidant activity of PARP inhibitors by methods with ABTS (2-2'-azinobis(3
      ethylbenzothiazoline 6-sulfonate) or DPPH (1,1-diphenyl-2-picrylhydrazyl) used as
      a radical because antioxidants also efficiently suppress methylmercury-induced
      cell death. The antioxidant activity of DPQ was the lowest among the tested PARP
      inhibitors. Taken together, our results indicate that DPQ effectively protects
      cells against methylmercury- and GSH depletion-induced death. Furthermore, they
      suggest that DPQ exerts its protective effect through a mechanism other than PARP
      inhibition and direct antioxidation, and that PARP activation is not involved in
      methylmercury-induced neuronal cell death.

PMID- 18627029
TI  - Cloning, expression, and functional analysis of rhesus monkey trace amine
      associated receptor 6: evidence for lack of monoaminergic association.
AB  - Several recent studies report an association between trace amine-associated
      receptor 6 (TAAR6) and susceptibility to schizophrenia and bipolar affective
      disorder in humans. However, endogenous TAAR6 agonists and the receptor signaling
      profile and brain distribution remain unclear. Here, we clone TAAR6 from the
      rhesus monkey and use transfected cells to investigate whether this receptor
      interacts with brain monoamines and a psychostimulant drug to trigger cAMP
      signaling or extracellular signal-regulated kinase (ERK) phosphorylation, while
      investigating its expression profile in the rhesus monkey brain. Unlike TAAR1,
      rhesus monkey TAAR6 did not alter cAMP levels in response to 10 microM of
      monoamines (dopamine, norepinephrine, serotonin, beta-phenylethylamine (beta
      PEA), octopamine, tryptamine, and tyramine) or methamphetamine in stably
      transfected cells in vitro. Real-time cell electronic sensing analysis indicated
      that the receptor did not alter cell impedance or change the effect of forskolin
      on cell impedance at exposure to 20 microM of each monoamine, suggesting a lack
      of either Gs or Gi-linked signaling. Whereas kappa opioid receptor activation led
      to ERK phosphorylation at exposure to 1 microM U69593, rhesus monkey TAAR6 had no
      such effect at exposure to 10 microM of monoamines or methamphetamine. Membrane
      and cell surface localization of TAAR6 was confirmed by immunocytochemistry,
      biotinylation, and Western blot testing with a TAAR6 antibody in the transfected
      cells. Real-time reverse transcriptase-polymerase chain reaction amplification
      showed that TAAR6 mRNA was undetectable in selected rhesus monkey brain regions.
      Together, the data reveal that TAAR6 is unresponsive to brain monoamines and is
      not expressed in rhesus monkey brain monoaminergic nuclei, suggesting TAAR6 lacks
      direct association with brain monoaminergic neuronal function.

PMID- 18627030
TI  - Histamine-induced Ca2+ entry in human astrocytoma U373 MG cells: evidence for
      involvement of store-operated channels.
AB  - Glial and glia-derived cells express a variety of receptors for neurotransmitters
      and hormones, the majority of which evoke both Ca(2+) release from intracellular
      stores and Ca(2+) entry across the plasma membrane. We investigated the links
      between histamine H(1) receptor activation, Ca(2+) release from intracellular
      stores and Ca(2+) influx in human astrocytoma U373 MG cells. Histamine, through a
      H(1) receptor-mediated effect, evoked an increase in cytoplasmic free calcium
      concentration ([Ca(2+)](i)) that occurred in two phases: an initial, transient,
      increase owing to Ca(2+) mobilization from intracellular pools, and a second,
      sustained increase dependent on both Ca(2+) influx and continuous receptor
      occupancy. The characteristics of histamine-induced increases in [Ca(2+)](i) were
      similar to the capacitative entry evoked by emptying of the Ca(2+) stores with
      thapsigargine, and different from that observed when Ca(2+) influx was activated
      with OAG (1-oleoyl-2-acetyl-sn-glycerol), a diacylglycerol (DAG) analog. OAG
      application or increased endogenous DAG, resulting from DAG kinase inhibition,
      reduced the histamine-induced response. Furthermore, activation of the DAG
      target, protein kinase C (PKC), by TPA (12-O-tetradecanoyl 4beta-phorbol 13alpha
      acetate) resulted in inhibition of the histamine-induced Ca(2+) response, an
      action prevented by PKC inhibitors. By using reverse transcriptase-polymerase
      chain reaction analysis, mRNAs for transient receptor potential channels (TRPCs)
      1, 4, and 6 as well as for STIM1 (stromal-interacting molecule) and Orai1 were
      found to be expressed in the U373 MG cells, and confocal microscopy using
      specific antibodies revealed the presence of the corresponding proteins.
      Therefore, TRPCs may be candidate proteins forming store-operated channels in the
      U373 MG cell line. Further, our results confirm the involvement of PKC in the
      regulation of H(1) receptor-induced responses and point out to the existence of a
      feedback mechanism acting via PKC to limit the increase in [Ca(2+)](i).

PMID- 18627031
TI  - Acute brain cytokine responses after global birth hypoxia in the rat.
AB  - The main cause of hypoxic/ischemic brain damage in term human neonates is
      intrauterine asphyxia, in which the whole body is subjected to hypoxia.
      Inflammatory cytokines are thought to play an important role in modulating
      hypoxic/ischemic damage in immature brain. Evidence for this from animal models
      is based mainly on studies that used a model of carotid artery ligation with
      hypoxia in postnatal rats. However, little is known about the role of cytokines
      in brain injury after whole-body hypoxia at the time of birth. This study used a
      well-established rat model of global birth hypoxia to assess mRNA and protein
      expression of three key proinflammatory cytokines, interleukin-1beta (IL-1beta),
      IL-6, and tumor necrosis factor-alpha, (TNF-alpha) in the brain, liver, and
      kidney of neonates. We observed decreased IL-1beta and TNF-alpha protein, and
      decreased IL-6 mRNA in brains of neonates in the 2 hr after birth hypoxia but
      increased IL-6 and IL-1beta in liver compared with vaginally born controls.
      Increasing the severity of the insult by increasing the period of anoxic exposure
      further decreased brain IL-1beta, whereas delivering anoxia under hypothermic
      conditions, known to be neuroprotective, attenuated the decrease in brain IL
      1beta. These data suggest that decreased brain levels of inflammatory cytokines
      may modulate central nervous system responses to global birth hypoxia in rats.
      Our findings of decreased brain cytokine expression after global birth hypoxia
      contrast with reports of increased brain cytokines after carotid artery ligation
      with hypoxia in postnatal rats; possible reasons for these differences are
      discussed.

PMID- 18627033
TI  - Adenosine produced by neurons is metabolized to hypoxanthine by astrocytes.
AB  - Adenosine (ADO) is an important neuromodulator in brain. During
      pathophysiological events such as stroke or brain trauma, ADO levels can increase
      up to 100-fold. We tested the hypothesis that astrocytes are important for the
      removal of ADO produced by neurons and for the metabolism of ADO to inosine (INO)
      and hypoxanthine (HX). We used four different cell culture preparations: cortical
      neurons, cortical astrocytes, cocultures of neurons and astrocytes, and neurons
      transiently cocultured with astrocytes on transwell filters. These cultures were
      treated with N-methyl-D-aspartate (NMDA), because NMDA receptor activation is a
      common factor among many causes of neurotoxicity. NMDA significantly increased
      extracellular ADO, INO, and HX levels from cultured cortical neurons by 3-, 3.5-,
      and 2-fold, respectively. In cocultures, NMDA significantly increased INO, by 4.5
      fold, and HX, by 3-fold, but did not increase ADO levels. There was no NMDA
      evoked purine production from astrocytes. Inhibition of purine nucleoside
      phosphorylase (PNP) significantly decreased HX production from both neurons and
      cocultures to less than 30% of control levels. The transient addition of
      astrocytes to neurons during NMDA treatment significantly increased HX and
      decreased ADO levels compared with neurons alone. In addition, increasing the
      number of astrocytes was directly correlated with an increased capacity of ADO
      metabolism to INO and HX. In conclusion, NMDA evoked the production of ADO, INO,
      and HX from neurons. In the presence of astrocytes, there was significantly less
      ADO and more HX produced. Thus, ADO produced by neurons is subject to metabolism
      by astrocytes, a process that may limit its neuromodulatory actions.

PMID- 18627032
TI  - Defective insulin signaling pathway and increased glycogen synthase kinase-3
      activity in the brain of diabetic mice: parallels with Alzheimer's disease and
      correction by insulin.
AB  - We have evaluated the effect of peripheral insulin deficiency on brain insulin
      pathway activity in a mouse model of type 1 diabetes, the parallels with
      Alzheimer's disease (AD), and the effect of treatment with insulin. Nine weeks of
      insulin-deficient diabetes significantly impaired the learning capacity of mice,
      significantly reduced insulin-degrading enzyme protein expression, and
      significantly reduced phosphorylation of the insulin-receptor and AKT.
      Phosphorylation of glycogen synthase kinase-3 (GSK3) was also significantly
      decreased, indicating increased GSK3 activity. This evidence of reduced insulin
      signaling was associated with a concomitant increase in tau phosphorylation and
      amyloid beta protein levels. Changes in phosphorylation levels of insulin
      receptor, GSK3, and tau were not observed in the brain of db/db mice, a model of
      type 2 diabetes, after a similar duration (8 weeks) of diabetes. Treatment with
      insulin from onset of diabetes partially restored the phosphorylation of insulin
      receptor and of GSK3, partially reduced the level of phosphorylated tau in the
      brain, and partially improved learning ability in insulin-deficient diabetic
      mice. Our data indicate that mice with systemic insulin deficiency display
      evidence of reduced insulin signaling pathway activity in the brain that is
      associated with biochemical and behavioral features of AD and that it can be
      corrected by insulin treatment.

PMID- 18627034
TI  - Minocycline in cerebral malaria.

PMID- 18627035
TI  - Topology and patch-clamp analysis of the sodium channel in relationship to the
      anti-lipid a antibody in campylobacteriosis.
AB  - An infecting strain VLA2/18 of Campylobacter jejuni was obtained from an
      individual with campylobacteriosis and used to prepare chicken sera by
      experimental infection to investigate the role of serum anti-ganglioside
      antibodies in Guillain-Barre syndrome. Both sera of the patient and chicken
      contained anti-ganglioside antibodies and anti-Lipid A (anti-Kdo2-Lipid A)
      antibodies directed against the lipid A portion of the bacterial
      lipooligosaccharide. The anti-Kdo2-Lipid A activities inhibited voltage-gated Na
      (Nav) channel of NSC-34 cells in culture. We hypothesized that anti-Kdo2-Lipid A
      antibody acts on the functional inhibition of Nav1.4. To test this possibility, a
      rabbit peptide antibody (anti-Nav1.4 pAb) against a 19-mer peptide
      (KELKDNHILNHVGLTDGPR) on the alpha subunit of Nav1.4 was produced. Anti-Nav1.4
      pAb was cross-reactive to Kdo2-Lipid A. Anti-Kdo2-lipid A antibody activity in
      the chicken serum was tested for the Na(+) current inhibition in NSC-34 cells in
      combination with mu-Conotoxin and tetrodotoxin. Contrary to our expectations, the
      anti-Kdo2-Lipid A antibody activity was extended to Nav channels other than
      Nav1.4. By overlapping structural analysis, it was found that there might be
      multiple peptide epitopes containing certain dipeptides showing a structural
      similarity with v-Lipid A. Thus, our study suggests the possibility that there
      are multiple epitopic peptides on the extracellular domains of Nav1.1 to 1.9, and
      some of them may represent target sites for anti-Kdo2-Lipid A antibody, to induce
      neurophysiological changes in GBS by disrupting the normal function of the Nav
      channels.

PMID- 18627036
TI  - A report of a patient with interstitial deletion of 15q22: further delineation of
      a new micro deletion syndrome.

PMID- 18627037
TI  - Evaluation of prenatal-onset osteochondrodysplasias by ultrasonography: a
      retrospective and prospective analysis.
AB  - The osteochondrodysplasias or skeletal dysplasias are a heterogenous group of
      over 350 distinct disorders of skeletogenesis. Many manifest in the prenatal
      period, making them amenable to ultrasound prenatal diagnosis. A retrospective
      analysis evaluated 1,500 cases referred to the International Skeletal Dysplasia
      Registry (ISDR) to determine the relative frequency of specific
      osteochondrodysplasias and correlation of ultrasound versus radiographic
      diagnoses for these disorders. Within the retrospective cohort of 1,500 cases,
      85% of the referred cases represented well-defined skeletal dysplasias, and the
      other 15% of cases were a mixture of genetic syndromes and probable early-onset
      intrauterine growth restriction. The three most common prenatal-onset skeletal
      dysplasias were osteogenesis imperfecta type 2, thanatophoric dysplasia and
      achondrogenesis 2, accounting for almost 40% of the cases. In a prospective
      analysis of 500 cases using a standardized ultrasound approach to the evaluation
      of these disorders, the relative frequencies of osteogenesis imperfecta type 2,
      thanatophoric dysplasia and achondrogenesis 2 were similar to the retrospective
      analysis. This study details the relative frequencies of specific prenatal-onset
      osteochondrodysplasias, their heterogeneity of prenatal-onset skeletal disorders
      and provides a standardized prenatal ultrasound approach to these disorders which
      should aid in the prenatal diagnosis of fetuses suspected of manifesting skeletal
      dysplasias.

PMID- 18627039
TI  - Spondylocostal dysostosis in a pregnancy complicated by confined placental
      mosaicism for tetrasomy 9p.
AB  - The spondylocostal dysostoses (SCD) are a clinically and genetically
      heterogeneous group of disorders characterized by defects of vertebral
      segmentation and rib abnormalities. We report on the diagnosis of two siblings
      with SCD. Diagnosis was first made in a female infant following a pregnancy that
      was complicated by early fetal hydrops and a nuchal translucency of 8.2 mm in the
      first trimester. The clinical picture was complicated by the co-existent
      diagnosis of confined placental mosaicism (CPM) for tetrasomy 9p. To our
      knowledge, this is the first report of CPM for tetrasomy 9p. Postnatally the
      diagnosis of SCD was made on the basis of radiographic findings comprising
      multiple anomalies of the cervical and thoracic vertebrae and multiple fused and
      dysplastic ribs. Radiographic investigation of other family members showed that
      the infant's 4-year-old sibling had fusion of four ribs on the right side,
      indicating a less severe form of SCD. Testing of the genes DLL3, MESP2, and LFNG
      did not identify a mutation, suggesting that the siblings may have a new
      molecular subtype of SCD.

PMID- 18627040
TI  - Clinical variability in acro-cardio-facial-syndrome.
AB  - We report on a 25-year-old man with ectrodactyly and genital anomalies whose
      parents are first cousins. Their second child died 4 days after birth with severe
      limb defects and imperforate anus. Our patient may represent clinical variability
      of the acro-cardio-facial syndrome.

PMID- 18627038
TI  - Secondary medical diagnosis in fragile X syndrome with and without autism
      spectrum disorder.
AB  - This study examined whether secondary medical diagnoses that affect CNS function
      (i.e., seizures, malformations, or genetic disorders), are more likely to occur
      in individuals with fragile X syndrome (FXS) and autism spectrum disorder (FXS +
      ASD) or FXS alone. Ninety males (3-25 years) with FXS or FXS + ASD were evaluated
      for secondary medical diagnoses by medical history and examination. A significant
      difference in the incidence of medical problems was found between patients with
      FXS + ASD (38.6%) and FXS alone (18.2%, P < 0.05). Medical problems that affect
      the CNS are more likely to occur in those with FXS + ASD and it is probable that
      additional brain dysfunction associated with these medical problems enhance the
      risk of autism in those with FXS.

PMID- 18627042
TI  - Aging in people with specific genetic syndromes: Rett syndrome.
AB  - The aging process of people with intellectual disabilities has been a topic of
      interest in recent years. Good knowledge of the specific healthcare problems in
      adults with intellectual disabilities and anticipating on these problems are
      important issues in providing support and healthcare for these persons.
      Nevertheless little is known about the aging process of people with specific
      syndromes, like Rett syndrome. In association with the Dutch Rett syndrome parent
      association, 70 postal questionnaires were sent to the contact persons of the
      females aged at least 16 years with a clinical diagnosis of Rett syndrome. The
      questionnaire consisted of general questions, questions about living conditions,
      skills, physical and psychiatric morbidity. The response rate was 76% (n = 53).
      In general adults with Rett syndrome seemed to be reasonably healthy, whereas
      neurological, respiratory and behavioral morbidity appeared to be of great
      influence. High care dependency was confirmed. In contrast with underweight,
      overweight showed to be an under-ascertained feature. The general disorder
      profile was confirmed, considering the increase with age regarding kyphosis and
      the better communication and autonomic dysfunction in the oldest age group
      compared to the younger age groups. Features of autonomic dysfunction deserve
      more medical attention, especially the interrelation between quality of sleep,
      respiration and behavior in Rett syndrome. Longitudinal studies including
      genotype-phenotype analyses are needed for insight in individual changes in
      support needs and health.

PMID- 18627041
TI  - Haplotype analysis at the FRAXA locus in an Indian population.
AB  - The FRAXA locus is flanked by three polymorphic STR markers DXS548, FRAXAC1, and
      FRAXAC2. Allele frequencies of these markers were determined on a population
      representing the eastern part of India comprising of 69 normal controls and 69
      unrelated subjects with mental retardation, among whom 21 were fragile X
      patients. These frequencies were compared with published data on other Indian
      population and the major populations of the world. The allele and haplotype
      distribution of the studied population were significantly different in some
      respects from the major populations of the world. The increase of
      heterozygosities in fragile X samples (DXS548 67.5%, FRAXAC1 63.5%, FRAXAC2
      68.5%) relative to the controls (DXS548 63.3%, FRAXAC1 51.0%, FRAXAC2 67.2%)
      suggests a multimodal distribution of fragile X associated alleles. Haplotype
      analyses with DXS548 and FRAXAC1 markers revealed that haplotype distribution in
      the normal controls and fragile X groups were significantly different, suggesting
      a weak founder effect.

PMID- 18627043
TI  - Limb-mammary syndrome (LMS) associated with internal female genitalia dysgenesia:
      a new genotype/phenotype correlation?

PMID- 18627044
TI  - Be careful with familial unbalanced chromosome abnormalities!

PMID- 18627045
TI  - Additional EFNB1 mutations in craniofrontonasal syndrome.

PMID- 18627047
TI  - SOX10 mutation in Waardenburg syndrome type II.

PMID- 18627048
TI  - Genital anomalies in a patient with Treacher Collins syndrome.

PMID- 18627046
TI  - Matrix extracellular phosphoglycoprotein (MEPE) correlates with serum phosphorus
      prior to and during octreotide treatment and following excisional surgery in
      hypophosphatemic linear sebaceous nevus syndrome.

PMID- 18627049
TI  - A new case of proximal monosomy 1p36, extending the phenotype.

PMID- 18627050
TI  - Clinical and genetic distinction of Schimke immuno-osseous dysplasia and
      cartilage-hair hypoplasia.

PMID- 18627051
TI  - De novo and complex imbalanced chromosomal rearrangements revealed by array CGH
      in a patient with an abnormal phenotype and apparently "balanced" paracentric
      inversion of 14(q21q23).
AB  - Paracentric inversions are one of the common chromosomal rearrangements typically
      associated with a normal phenotype. However, if dosage-sensitive genes are
      disrupted by the breakpoints, an abnormal phenotype could result. Detection of
      paracentric inversions often relies on careful high resolution banding, which has
      limited sensitivity. We report here cytogenetic studies performed on a 4-year-old
      female patient with global developmental delay, hypotonia, and dysmorphic
      features. The initial cytogenetic evaluation by G-banding revealed a de novo
      inversion of chromosome 14. Subsequent array CGH analysis using both a targeted
      BAC array and a high-resolution oligonucleotide array revealed microdeletions at
      the breakpoints of 14q21.1 (0.8 Mb) and 14q23.1 (0.9 Mb). Unexpectedly, a
      microdeletion in the region of 16q23.1 (1.3 Mb) was also identified, which
      overlaps with the common fragile site FRA16D. Parental chromosome and FISH
      analyses were normal, supporting the conclusion that these microdeletions were de
      novo in the patient and likely contributed to her abnormal phenotype. The case
      report presented illustrates the value of using high-resolution microarray
      analysis for phenotypically abnormal individuals with apparently balanced
      chromosomal rearrangements, including inversions.

PMID- 18627052
TI  - A case of Lelis syndrome with hystrix-like ichthyosis.

PMID- 18627053
TI  - Analytical and clinical validity of whole-genome oligonucleotide array
      comparative genomic hybridization for pediatric patients with mental retardation
      and developmental delay.
AB  - We performed a pilot study to establish the analytical and clinical validity of
      whole genome oligonucleotide array comparative genomic hybridization (oaCGH)
      using the 44,000 oligonucleotide array from Agilent Technologies. DNA specimens
      from 10 patients with different chromosomal abnormalities were used as the test
      group and sex mismatched normal male or female DNA as references. A series of DNA
      mixtures containing 50%, 33%, and 25% of a known deletion was generated to
      evaluate the analytical capacity of oaCGH on detecting mosaic pattern. Receiver
      operating characteristic (ROC) curves were computed to evaluate sensitivity,
      specificity, and analytical resolution for detecting deletions, duplications, and
      mosaic patterns. The oaCGH detected the chromosomally recognized deletions,
      duplications, and additional genomic aberrations. Fluorescent in situ
      hybridization (FISH) assays using targeted BAC clone probes confirmed oaCGH
      findings. Failure in detecting marker chromosomes, a polymorphic inversion, and a
      Robertsonian translocation was also noted. The oaCGH achieved 99% sensitivity and
      99% specificity with a resolution of 300-500 Kb. It also demonstrated 85%
      sensitivity and 95% specificity in detecting 50% mosaicism; however, increased
      test-to-test variations and reduced sensitivity were noted as the mosaic
      percentage decreased. Chromosome and oaCGH analyses on 50 pediatric patients with
      mental retardation (MR) and developmental delay (DD) delineated the genomic
      content of chromosomal abnormalities in nine cases, pathogenic genomic disorders
      in three cases and benign genomic variants in six cases. These results affirmed
      the analytical and clinical validity of oaCGH and prompted a cytogenomic
      algorithm to integrate oaCGH, chromosome and FISH analyses for genetic diagnosis.

PMID- 18627054
TI  - An intronic mutation in DKC1 in an infant with Hoyeraal-Hreidarsson syndrome.

PMID- 18627055
TI  - A 3 Mb deletion in 14q12 causes severe mental retardation, mild facial
      dysmorphisms and Rett-like features.
AB  - The present report describes a 7-year-old girl with a de novo 3 Mb interstitial
      deletion of chromosome 14q12, identified by oligo array-CGH. The region is gene
      poor and contains only five genes two of them, FOXG1B and PRKD1 being deleted
      also in a previously reported case with a very similar phenotype. Both patients
      present prominent metopic suture, epicanthic folds, bulbous nasal tip, tented
      upper lip, everted lower lip and large ears and a clinical course like Rett
      syndrome, including normal perinatal period, postnatal microcephaly, seizures,
      and severe mental retardation. FOXG1B (forkhead box G1B) is a very intriguing
      candidate gene since it is known to promote neuronal progenitor proliferation and
      to suppress premature neurogenesis and its disruption is reported in a patient
      with postnatal microcephaly, corpus callosum agenesis, seizures, and severe
      mental retardation.

PMID- 18627056
TI  - Molecular and clinical characterization of two patients with Prader-Willi
      syndrome and atypical deletions of proximal chromosome 15q.
AB  - Prader-Willi syndrome (PWS) is caused by the disturbed expression of genes from
      the imprinted region of 15q11-q13, but the specific contributions of individual
      genes remain unknown. Most paternal PWS deletions are bracketed by recurrent
      breakpoints BP1 or BP2 and BP3. Atypical deletions are very rare. In the present
      work, we describe the molecular analysis of two patients with atypical deletions
      using microsatellite analysis, methylation-specific MLPA, and microarray CGH. A
      deletion of about 2 Mb in Patient 1 started at BP2 and ended in the middle of the
      typically deleted region within the UBE3A gene. The deletion in Patient 2 started
      1.3 Mb distal from BP2 within the C15ORF2 gene, extended over 9.5 Mb, and ended
      within the AVEN gene in proximal 15q14. In Patient 1 both deletion breakpoints
      involved repetitive regions, which precluded cloning of the junction and pointed
      to non-allelic homologous recombination as a possible mechanism of this
      rearrangement. The breakpoints in Patient 2 were sequenced, and their structure
      suggested non-homologous end joining as the most likely cause of this deletion.
      The phenotype of both patients did not depart significantly from the typical
      clinical picture of PWS, although some symptoms in Patient 2 were also
      reminiscent of the phenotype of individuals with the recently described 15q13.3
      microdeletion syndrome. Our findings support previous observations of relatively
      mild phenotypic effects resulting from deletions that extend distally from the
      PWS region and observations of the modest effects of different types of genetic
      defects on the spectrum and severity of symptoms in PWS.

PMID- 18627057
TI  - Monozygotic twins discordant for Proteus syndrome.
AB  - Proteus syndrome is a rare, complex disorder predominantly characterized by
      asymmetric overgrowth of body parts, connective tissue and epidermal nevi, and
      vascular malformations. General diagnostic criteria comprise mosaic distribution,
      sporadic occurrence, and progressive course. We report on Proteus syndrome in
      discordant monozygotic twins. The affected 9-year-old boy showed progressive
      postnatal overgrowth of his right leg and foot and asymmetric progressive
      overgrowth of single toes with a small cerebriform connective tissue nevus on his
      right fourth toe. The progressive course was documented by serial photographs
      over a period of 3 years. Twin monozygosity was determined by PCR-amplified short
      tandem repeat (STR) analysis, revealing complete concordance of all alleles in
      both twins. This observation, to our knowledge, is only the second case report of
      discordant Proteus syndrome in monozygotic twins. This supports the hypothesis
      that this rare condition is caused by a postzygotic mutational event resulting in
      mosaicism.

PMID- 18627058
TI  - Constitutional H19 hypermethylation in a patient with isolated cardiac tumor.
AB  - Beckwith-Wiedemann syndrome (BWS) is clinically and molecularly very
      heterogenous. Molecular findings characteristic of BWS have been reported in
      individuals with no or few associated features. We report on a child with
      isolated cardiac tumor and a constitutional H19 hypermethylation with none of the
      features of BWS.

PMID- 18627059
TI  - Fear of health insurance loss among individuals at risk for Huntington disease.
AB  - Genetic testing in Huntington disease, an inherited ultimately fatal
      neurodegenerative disorder, is infrequent despite wide availability. Factors
      influencing the decision to pursue testing are largely unknown. We conducted a
      prospective longitudinal observational study of 1,001 individuals in North
      America who were at risk for Huntington disease who had not pursued genetic
      testing prior to enrollment. We evaluated the rationale for remaining untested at
      baseline, determined the concerns of those who eventually pursued testing, and
      assessed the population's psychological attributes. We contrasted responses
      between those who did and did not pursue testing, and between United States and
      Canadian residents. The principal reasons for remaining untested were comfort
      with risk and uncertainty and the inability to "undo" knowledge gained. After
      enrollment, 83 individuals [8.3%] pursued genetic testing. Their greatest concern
      was losing health insurance, and 41.6% of them [vs. 6.7% of those who did not
      pursue testing; P < 0.001] reported paying out of pocket for testing or other
      medical services to conceal their genetic risk from their insurer/employer. Among
      individuals who were tested, more United States residents [46.1%] than Canadian
      residents [0.0%; P = 0.02] paid out of pocket for health services or genetic
      testing. Psychological attributes were similar among individuals who did and did
      not pursue testing. Individuals at risk for Huntington disease who pursued
      genetic testing feared losing medical insurance, and many paid out of pocket for
      medical services. Alleviating the fear of health insurance loss may help those
      who want to pursue genetic testing for many other conditions. [ClinicalTrials.gov
      number, NCT0052143].

PMID- 18627060
TI  - Mental health and quality of life after genetic testing for Huntington disease: a
      long-term effect study in Germany.
AB  - Predictive genetic testing for Huntington disease (HD) might cause severe short
      term psychological reactions in patients with poor mental health. Very few
      studies exist on the long-term effects of genetic HD testing. The aim of this
      study was to assess mental health and quality of life in persons who were tested
      for HD mutation, to compare mental health depending on the result of the genetic
      test (non-carriers, gene carriers, and patients with HD) and to identify
      predictors of mental health and quality of life via linear regression. The data
      were collected by self-report questionnaires. In total, 121 individuals
      participated in this study: 52 were non-carriers, 54 were gene carriers, and 15
      were gene carriers suffering from HD. Non-carriers and gene carriers showed
      better mental health and quality of life than HD-patients but did not differ from
      each other. In non-carriers four variables predicted increased depression and low
      mental quality of life: low perceived social support, no intimate relationship,
      female sex and younger age. For gene carriers three predictors were found: low
      perceived social support, the expectation of an unfavorable genetic test result
      before the testing procedure and being childless. To prevent detrimental effects
      of HD testing on mental health and mental quality of life, specific attention
      should be paid to persons with limited social networks during genetic counseling.
      Assessment of expectations related to the test result and mental health prior to
      a genetic testing procedure may help to identify gene carriers at risk of poor
      coping after an unfavorable test result.

PMID- 18627061
TI  - Radiological evolution in IMAGe association: a case report.
AB  - IMAGe association is a recently recognized multi-system disorder of unknown
      etiology. IMAGe is a mnemonic acronym that stands for Intrauterine growth
      retardation, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital
      anomalies (OMIM 300290). Suspicion for the disorder is readily raised by the
      distinctive clinical and endocrinological constellation, and radiological
      identification of metaphyseal dysplasia is crucial for the diagnosis. However,
      knowledge of the onset, evolution, severity, and variation of the metaphyseal
      dysplasia is currently limited. We illustrate the radiological evolution of an
      affected girl from her premature birth to early childhood. Her initial skeletal
      changes included thin ribs, delayed ossification of the juxtatruncal bones, and
      delayed epiphyseal ossification. The former two became less conspicuous during
      infancy. Metaphyseal dysplasia was not discerned at birth. However, mild
      metaphyseal cupping, sclerosis and longitudinal striations became manifest in
      late infancy, and then progressed with age. It is thought that the skeletal
      alterations in IMAGe association encompass retarded endochondral ossification
      normalized later on and mild metaphyseal dysplasia of postnatal onset.

PMID- 18627062
TI  - Schilbach-Rott/blepharofacioskeletal syndrome in a Brazilian patient.
AB  - We report on a 4-year-old girl with blepharophimosis, a typical facial gestalt
      and skeletal abnormalities seen in the blepharofacioskeletal syndrome (BFSS). A
      comparative review with previous cases provides further evidence that BFSS and
      Schilbach-Rott syndrome (SRS) are the same condition.

PMID- 18627063
TI  - Marshall-Smith syndrome and septo-optic dysplasia: an unreported association.
AB  - Marshall-Smith syndrome is characterized by advanced bone age, failure to thrive,
      respiratory problems, dysmorphic facial features, and variable mental
      retardation. Less than 40 cases have been reported in the literature, mostly as
      single case reports or small series. We describe a female newborn who, in
      addition to demonstrating many of the well described features of Marshall-Smith
      syndrome, had septo-optic dysplasia.

PMID- 18627064
TI  - Monozygotic twins discordant for trisomy 21 and maternal 21q inheritance: a
      complex series of events.
AB  - We report on a monochorionic/diamniotic twin pregnancy discordant for trisomy 21.
      Amniocentesis (at 13(5/7) weeks) was performed following ultrasound signs of
      hydrops and cystic hygroma in twin 1 (T1). Prenatal karyotype showed non-mosaic
      trisomy 21 in T1 (47,XX,+21[7]), and low-grade mosaic trisomy 21 in twin 2 (T2)
      (47,XX,+21[2]/46,XX[19]). Post mortem examination of fetal skin, kidneys and
      lungs confirmed trisomy 21 in T1 (47,XX,+21[548]) and the placenta
      (47,XX,+21[200]). T2 had a normal karyotype (46,XX[648]). Analysis of
      microsatellite polymorphisms in multiple samples from the placenta, hand, lungs,
      kidneys and the umbilical cords of both twins confirmed monozygosity for all loci
      tested, and trisomy 21 in T1. Unexpectedly, T1 and T2 inherited different
      maternal alleles for markers of the most distal 4 Mbp of 21q. At least four
      successive events are needed to explain the genetic status of both twins and
      include maternal MI premature chromatids separation or maternal II meiotic
      nondisjunction and post-zygotic events such as, chromosome rescue,
      nondisjunction, an/or recombination.

PMID- 18627065
TI  - Disruption of the TCF4 gene in a girl with mental retardation but without the
      classical Pitt-Hopkins syndrome.
AB  - We have characterized a de novo balanced translocation t(18;20)(q21.1;q11.2) in a
      female patient with mild to moderate mental retardation (MR) and minor facial
      anomalies. Breakpoint-mapping by fluorescence in situ hybridization indicated
      that on chromosome 18, the basic helix-loop-helix transcription factor TCF4 gene
      is disrupted by the breakpoint. TCF4 plays a role in cell fate determination and
      differentiation. Only recently, mutations in this gene have been shown to result
      in Pitt-Hopkins syndrome (PHS), defined by severe MR, epilepsy, mild growth
      retardation, microcephaly, daily bouts of hyperventilation starting in infancy,
      and distinctive facial features with deep-set eyes, broad nasal bridge, and wide
      mouth with widely spaced teeth. Breakpoint mapping on the derivative chromosome
      20 indicated that here the rearrangement disrupted the chromodomain helicase DNA
      binding protein 6 (CHD6) gene. To date, there is no indication that CHD6 is
      involved in disease. Our study indicates that TCF4 gene mutations are not always
      associated with classical PHS but can give rise to a much milder clinical
      phenotype. Thus, the possibility exists that more patients with a less severe
      encephalopathy carry a mutation in this gene.

PMID- 18627066
TI  - Mechanisms of imprinting of the Prader-Willi/Angelman region.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct
      neurodevelopmental disorders, each caused by several genetic and epigenetic
      mechanisms involving the proximal long arm of chromosome 15. Lack of a functional
      paternal copy of 15q11-q13 causes PWS; lack of a functional maternal copy of
      UBE3A, a gene within 15q11-q13, causes AS. This region of chromosome 15 contains
      a number of imprinted genes that are coordinately regulated by an imprinting
      center (PWS/AS-IC) that contains two functional elements, the PWS-SRO and the AS
      SRO. A chromosome lacking the PWS-SRO has the maternal state of gene activity and
      epigenetic modification after either maternal or paternal transmission; a
      chromosome lacking the AS-SRO but containing the PWS-SRO has the paternal state
      of gene activity and epigenetic modification after either maternal or paternal
      transmission. The maternal state of chromosome 15q11-q13 is associated with
      methylation of the PWS-SRO, while the paternal state is associated with lack of
      methylation of the PWS-SRO. Although most models of PWS/AS region imprinting
      assume that the PWS-SRO is methylated during oogenesis and that this methylation
      of the maternal PWS-SRO is maintained after fertilization, several lines of
      evidence suggest that the maternal PWS-SRO is in fact not methylated until after
      fertilization. Imprinting defects affecting the PWS/AS region can arise from
      failure to demethylate the PWS-SRO in the male germ line, from failure to
      methylate the maternal PWS-SRO, or from failure to maintain PWS-SRO methylation
      after fertilization.

PMID- 18627067
TI  - Homozygous deletions of a copy number change detected by array CGH: a new cause
      for mental retardation?
AB  - We describe two unrelated patients with mental retardation and normal karyotypes
      found to have relatively large homozygous deletions (>150 kb) of different
      regions detected by array comparative genomic hybridization (aCGH). Patient 1
      showed a 157-214 kb deletion at 8q24.2, containing BAC clone RP11-17M8. This
      patient was born to phenotypically normal parents and has microcephaly,
      distinctive craniofacial features, brachymetacarpia, brachymetatarsia and severe
      mental retardation. This BAC clone is listed as a copy number variant on the
      Database of Genomic Variants (http://projects.tcag.ca/variation/). Heterozygosity
      for the deletion was found in the mother (father is deceased) and uniparental
      disomy of chromosome 8 was excluded. Patient 2 showed a 812-902 kb deletion at
      12q21.1, containing BAC clone RP11-89P15. This region was not listed in any
      public database as a known variant. This patient has mild craniofacial dysmorphic
      features, bifid uvula, peripheral pulmonic stenosis and developmental delay.
      Heterozygosity for this deletion was confirmed in the phenotypically normal
      parents and two normal siblings, but surprisingly, homozygosity for the deletion
      in an apparently normal younger sibling brings into question whether this large
      homozygous copy number change (CNC) is causal. Homozygous deletions of CNCs have
      not previously been reported in association with a phenotype or mental
      retardation. These cases represent homozygosity for presumably benign CNCs, and
      while causality for the phenotypes cannot be confirmed, similar deletions are
      bound to be identified more frequently as aCGH is used with increasing
      regularity. Such homozygous deletions should be viewed as potentially clinically
      relevant.

PMID- 18627069
TI  - Thermal inactivation of immobilized penicillin acylase in the presence of
      substrate and products.
AB  - Inactivation of immobilized penicillin acylase has been studied in the presence
      of substrate (penicillin G) and products (phenylacetic acid and 6
      aminopenicillanic acid), under the hypothesis that substances which interact with
      the enzyme molecule during catalysis will have an effect on enzyme stability. The
      kinetics of immobilized penicillin acylase inactivation was a multistage process,
      decay constants being evaluated for the free-enzyme and enzyme complexes, from
      whose values modulation factors were determined for the effectors in each enzyme
      complex at each stage. 6-Aminopenicillanic acid and penicillin G stabilized the
      enzyme in the first stage of decay. Modulation factors in that stage were 0.96
      for penicillin G and 0.98 for 6-aminopenicillanic acid. Phenylacetic acid
      increased the rate of inactivation in both stages, modulating factors being -2.31
      and -2.23, respectively. Modulation factors influence enzyme performance in a
      reactor and are useful parameters for a proper evaluation.

PMID- 18627070
TI  - Correlations for the partition behavior of proteins in aqueous two-phase systems:
      effect of overall protein concentration.
AB  - The effect of protein concentration in partitioning in PEG/salt aqueous two-phase
      systems has been investigated. PEG 4000/phosphate systems in the presence of 0%
      w/w and 8.8% w/w NaCl have been evaluated using amyloglucosidase, subtilisin, and
      trypsin inhibitor. Also, a PEG 4000/phosphate system with 3% w/w NaCl was used
      for alpha-amylase. The concentration of the protein in each of the phases
      affected its partition behavior. The pattern for the individual proteins was
      dependent on their physicochemical properties. In the top phase, maximum protein
      concentration was determined mainly by a steric exclusion effect of PEG, and
      hydrophobic interaction between PEG and proteins. In the bottom phase, maximum
      concentration was determined mainly by a salting-out effect of the salts present.
      As the ionic strength was increased in the systems the concentration in the top
      phase increased for all proteins. In the bottom phase an increase in ionic
      strength increased the salting-out effect. Amyloglucosidase had a very low
      maximum concentration in the PEG-rich top phase which was probably due to its
      large size (steric exclusion) and low hydrophobicity, and a high concentration in
      the salt-rich bottom phase due to its high hydrophilicity. In the case of
      subtilisin and trypsin inhibitor, their high concentrations in the top phase were
      due to their hydrophobic nature (hydrophobic interaction with PEG) and small size
      (negligible steric exclusion). The maximum concentration in the bottom phase for
      trypsin inhibitor was lower than that of subtilisin which was probably due to its
      higher hydrophobicity and, hence, a stronger salting-out effect. The protein
      concentration in each of the two phases was correlated with a "saturation"-type
      equation. The partition coefficient could be satisfactorily predicted, as a
      function of the overall protein concentration, by the ratio between the
      "saturation" equations of the two individual phases. Better correlations were
      obtained when an empirical sigmoidal Boltzmann equation was fitted to the data,
      since in virtually all cases the partition coefficient is constant at low protein
      concentration (true partitioning) and changes to a different constant value at a
      high overall protein concentration.

PMID- 18627071
TI  - Optimization of physical parameters for cell attachment and growth on macroporous
      microcarriers.
AB  - The rates of cell attachment of the anchorage-dependent mammalian cell line Vero
      to the gelatin-based macroporous microcarrier Cultispher-G were determined under
      various conditions. An optimal rate of attachment (0.98 x 10(-2) min(-1))
      occurred by an intermittent stirring regimen of 3 min stirring at 40 rpm per 33
      min. This stirring regimen appeared to maximize cell-to-bead attachment and
      minimized cell aggregation which occurred at a broadly comparable rate.A further
      increase in the rate of cell-to-bead attachment occurred by preincubation of the
      microcarriers in serum-supplemented medium prior to cell inoculation in a serum
      free medium. However, serum supplementation (>5%) was required for maximal cell
      growth. The pH of the medium had little effect on cell attachment over a broad
      range (pH 7.1-8.0). An initial cell/bead inoculum of 30 ensured an even
      distribution of cells on the available microcarriers with a low proportion of
      unoccupied beads.The rate of cell attachment to Cultispher-G was an order of
      magnitude lower than the determined value for the charged dextran microcarrier
      Cytodex-1, which was measured as 9.05 x 10(-2) min(-1). The optimal conditions
      for cell attachment were significantly different for the two bead types. Cell
      attachment to the electrostatic surface of the Cytodex-1 microcarriers was highly
      dependent on pH and serum supplementation. Cell aggregation during attachment to
      the Cytodex-1 microcarriers was minimal because of the higher rate of cell
      microcarrier attachment.The porous nature of the Cultispher-G microcarriers
      allowed a maximum cell/bead loading of >1400, which was at least 3 times higher
      than equivalent loading of the cells on Cytodex-1. The Cultispher-G matrix also
      allowed the use of higher agitation rates (up to 100 rpm) in spinner flasks
      without affecting the cell growth rate or maximum cell density.

PMID- 18627072
TI  - Genetic manipulation of stationary-phase genes to enhance recombinant protein
      production in Escherichia coli.
AB  - Genetic manipulation of the host strain, by which cell physiology could be
      modulated, was exploited to enhance recombinant protein production in Escherichia
      coli. The effects of an inactivated stationary-phase gene (rmf or katF) on
      recombinant protein production in strains with two different expression systems
      (the pH-inducible and the lac promoters) were investigated. An improvement of
      recombinant protein production in the katF mutant at low growth rates was
      observed for both expression systems. A fourfold and a 30% increase in the
      volumetric recombinant protein activity were observed for the pH-inducible and
      the lac promoter system, respectively. The effect of the rmf mutation, on the
      other hand, depends on the expression system. A twofold increase in the
      volumetric recombinant protein activity was found for the pH-inducible promoter
      system, but there was no improvement for the lac promoter system. Improvement in
      culture performance for slow-growing cultures may have an impact on the design
      strategy of the host/vector system used in fed-batch cultures, where the specific
      growth rate is usually slow. The information may also be useful for developing
      optimal host/vector gene expression systems for recombinant protein production.

PMID- 18627073
TI  - Specific energy dissipation rate for fluidized-bed bioreactors.
AB  - An innovative hydrodynamic parameter, specific energy dissipation rate (omega),
      is proposed and defined as the energy dissipation at the biofilm surface (by
      erosive effect of flowing water surrounding the bioparticle) per unit volume of
      fluidized-bed bioreactor per unit time. From the simulated results, omega is
      varied with operating flow rate and bed expansion characteristics. The biofilm
      thickness (delta) is found to be inversely proportional to omega. A small omega
      value benefits the growth of a thick biofilm. Thus, at different stages (e.g.,
      during start-up and at different biofilm thicknesses) the model can be applied to
      predetermine a better operating scheme. The experimental results also show that
      the steady-state biofilm thickness measured in the upper and lower parts of the
      bioreactors is inversely proportional to omega values. Biofilm thickness and
      omega in the upper part of the bioreactors are respectively larger and smaller
      than those in the lower part. In addition, by referring to the published data,
      delta correlates well with omega, and thus the proposed model is well verified.

PMID- 18627074
TI  - A comparative study of the purity, enzyme activity, and inactivation by hydrogen
      peroxide of commercially available horseradish peroxidase isoenzymes A and C.
AB  - Horseradish peroxidase (HRP) is a commercially important enzyme that is available
      from a number of supply houses in a variety of grades of purity and isoenzymic
      combinations. The present article describes a comparative study made on nine HRP
      preparations. Six of these samples were predominantly composed of basic HRP, pl
      8.5, and three of acidic HRP, pl 3.5. Two of the basic preparations were of lower
      purity than the others. The apparent molar catalytic activity of basic HRP with
      0.5 mMABTS and 0.2 mM H(2)O(2) was around 950 s(-1) (about 770 s(-1) for the less
      pure samples) and with a 5 mM guaiacol and 0.6 mM H(2)O(2) was about 180 s(-1)
      for all the samples. A similar value (approximately 1000 s(-1)) was observed for
      acidic HRP but only at higher concentrations of ABTS (20 mM). With 20 mM guaiacol
      the molar catalytic activity of the acid isoenzyme was 65 s(-1). The apparent
      K(M) for ABTS of the acidic isoenzyme was 4 mM whereas for the basic isoenzyme it
      was 0.1 mM. All the enzymes were inactivated by H(2)O(2) when it was supplied as
      the only substrate. Under these conditions the partition ratio (r = number of
      catalytic cycles given by the enzyme before its inactivation), apparent
      dissociation constant (K(l)), and apparent rate constant of inactivation
      (k(inact)) were about twice as large for the acidic samples (1350, 2.6 mM, 9 x
      10(-3) s(-1)) as for the basic (650, 1.3 mM, 5 x 10(-3) s(-1)). The apparent
      catalytic constant (k(cat)) was 3-4 times larger, and the efficiency of catalysis
      (k(cat)/K(l)) was double for the acidic isoenzyme, but the efficiency of
      inactivation (k(inact)/K(l)) was similar. The data obtained provide useful
      information for those using HRP isoenzymes for biotechnological applications
      (e.g., biosensors, bioreactors, or assays).

PMID- 18627075
TI  - Dynamics and modeling of temperature-regulated gene product expression in
      recombinant yeast fermentation.
AB  - The dynamic response of temperature-regulated gene expression in the recombinant
      yeast Saccharomyces cerevisiae, strain XK1-C2 carrying plasmid pSXR125, to
      temperature changes during fed-batch and continuous (chemostat) cultures was
      studied. The production of the gene product, beta-galactosidase, in the yeast
      cell is sensitive to the growth temperature. Gene expression of this product was
      fully turned on or off by temperature shifts between 24 and 30 degrees C.
      However, the response for gene turn-on and turn-off in this recombinant yeast was
      slow, requiring from several hours to over 10 h to fully appear. The continuous
      reactor took 30-60 h after the temperature shift to reach a new steady state. A
      dynamic process model was developed to simulate the reactor and cell responses to
      temperature shift. A first-order model was used to account for the effect of
      dilution rate on the change of protein concentration in the chemostat. It was
      found that cell response in gene expression to temperature shift followed first
      order plus dead-time dynamics. Also, the response time for gene expression to
      temperature shift varied with specific growth rate or dilution rate of the
      continuous reactor. In general, the response was slower at a higher dilution rate
      and for gene turn-on than for gene turn-off.

PMID- 18627076
TI  - Steady-state solution of a two-species biofilm problem.
AB  - Through a thorough investigation of the boundary conditions for a general two
      species biofilm model, a simple and fast method for solving the steady-state case
      is developed and presented. The methods used may be extended to biofilm models in
      which more than two species are considered. Four different sets of boundary
      conditions are possible for the two-species biofilm model. Each set is shown to
      be asymptotically stable. A biofilm model describing the competition between
      autotrophic and heterotrophic bacteria and a biofilm model considering only
      Nitrosomonas and Nitrobacter are used for illustration. A parameter L(crit),
      critical film thickness for bacterial coexistence, is introduced from which
      criteria on the bulk concentrations for coexistence are derived. From these
      criteria it is seen that the thinner the biofilm, the more restrictive the
      conditions are for steady-state coexistence. For thin biofilms there may, in many
      cases, be no point in considering more than one species in the biofilm model.
      Furthermore, the gradients of the bacterial concentrations are in many cases
      negligible in thin biofilms, and the biofilm may then be assumed to be
      homogeneous. The criteria on the bulk concentrations together with the four sets
      of boundary conditions provide the necessary information for a direct solution of
      the steady-state two-species biofilm model by means of an ordinary differential
      and algebraic equation solver.

PMID- 18627077
TI  - Effect of the hydration state of supports before lyophilization on subtilisin-A
      activity in organic media.
AB  - Subtilisin-A was colyophilized with various types of support materials, such as
      Amberlite IRC-50, Celite545, chitosan, DEAE-cellulose, DOWEX-1, zeolite, glass
      bead, and polystyrene. The colyophilized enzyme was used for the optical
      resolution of racemic 1-phenylethylamine with 2,2,2-trifluoroethylbutyrate in 3
      methyl-3-pentanol. The enzyme activity in organic media changed dramatically
      according to the hydration state of the support materials before lyophilization.
      This effect was especially marked with supports of high water capacity
      (aquaphilicity), such as chitosan and DEAE-cellulose. By hydrating these supports
      of high aquaphilicity prior to lyophilization, subtilisin-A activity in organic
      media increased ca. 4-8 times, depending upon the supports used. This result
      suggests that the hydration state of aquaphilic support materials for
      colyophilization is critical to determining enzyme activity in organic solvents.

PMID- 18627078
TI  - Determination of monod kinetic coefficients for volatile hydrophobic organic
      compounds.
AB  - A new procedure is presented to determine Monod kinetic coefficients and the
      microbial yield coefficient for volatile hydrophobic compounds such as
      phenanthrene. Batch experiments were conducted with a mixed culture capable of
      degrading phenanthrene. The phenanthrene disappearance and carbon dioxide
      production were monitored with time. A maximum likelihood estimator was
      formulated to fit the set of equations that describe the system to the measured
      data. The model takes into account a number of processes such as partition onto
      the apparatus, volatilization, and partition onto the biomass. The parameters
      required to describe these processes were obtained by independent experiments.
      The yield coefficient could be determined within a small range. However, the
      specific growth rate and the half-saturation constant were found to vary widely,
      with pairs of them describing the system adequately. It was shown that partition
      and volatilization processes can significantly affect the determination of the
      yield and Monod kinetic coefficients and need to be taken into account.

PMID- 18627079
TI  - Enzymatic synthesis of a CCK-8 tripeptide fragment in organic media.
AB  - The enzymatic synthesis of the tripeptide derivative Z-Gly-Trp-Met-OEt is
      reported. This tripeptide is a fragment of the cholecystokinin C-terminal
      octapeptide CCK-8. Studies on the alpha-chymotrypsin catalyzed coupling reaction
      between Z-Gly-Trp-R(1) and Met-R(2) have focused on low water content media,
      using deposited enzyme on inert supports such as Celite and polyamide. The effect
      of additives (polar organic solvents), the acyl-donor ester structure, the C
      alpha protecting group of the nucleophile, enzyme loading, and substrate
      concentration were tested. The best reaction medium found was acetonitrile
      containing buffer (0.5%, v/v) and triethylamine (0.5%, v/v) using the enzyme
      deposited on Celite as catalyst (8 mg of alpha-chymotrypsin/g of Celite). A
      reaction yield of 81% was obtained with Z-Gly-Trp-OCam as acyl donor, at an
      initial concentration of 80 mM. The tripeptide synthesis was scaled up to the
      production of 2 g of pure tripeptide with an overall yield of 71%, including
      reaction and purification steps.

PMID- 18627080
TI  - Apparent zero-order kinetics of phenol biodegradation by substrate-inhibited
      microbes at low substrate concentrations.
AB  - The reaction kinetics for phenol biodegradation at low substrate concentrations
      can be estimated based on the analysis of changes in the dissolved oxygen
      concentration in the bulk liquid during biodegradation. The measured oxygen
      concentration changes with an interesting behavior as biodegradation proceeds.
      The oxygen concentration in the bulk liquid decreases rapidly in the early stages
      of degradation and subsequently decreases linearly and then rapidly recovers to
      the initial saturated level. Taking into account the oxygen transfer rate between
      gas and liquid phases and oxygen consumption rate by microbes, the change in the
      dissolved oxygen concentration can be simulated with an unsteady state mass
      balance equation and three kinetic models for the rate of phenol metabolism: a
      substrate-inhibited model; a zero-order model; and a combined model. In the
      combined model, it is assumed that, at phenol concentrations above 10 mg/L, the
      degradation rate is expressed by a substrate-inhibited model; whereas at
      concentrations below 10 mg/L the zero-order model is applied. It was found that
      the characteristics of the change in the dissolved oxygen concentration,
      especially the rapid increase at the end of degradation, can only be described by
      the combined kinetic model. This result suggests that conventional Haldane-type
      kinetics would be unsuitable for estimating the phenol consumption rate at low
      phenol concentrations, in particular, at concentrations less than 10 mg/L.

PMID- 18627082
TI  - Microscale-based modeling of polynuclear aromatic hydrocarbon transport and
      biodegradation in soil.
AB  - A mathematical model to describe polynuclear aromatic hydrocarbon (PAH)
      desorption, transport, and biodegradation in saturated soil was constructed by
      describing kinetics at a microscopic level and incorporating this description
      into macroscale transport equations. This approach is novel in that the
      macroscale predictions are made independently from a knowledge of microscale
      kinetics and macroscopic fluid dynamics and no adjustable parameters are used to
      fit the macroscopic response. It was assumed that soil organic matter, the
      principal site of PAH sorption, was composed of a continuum of compartments with
      a gamma distribution of desorption rate coefficients. The mass transport of
      substrates and microorganisms in a mesopore was described by diffusion and that
      in a macropore by one-dimensional advection and dispersion. Naphthalene was
      considered as a test PAH compound for initial model simulations. Three mechanisms
      of naphthalene biodegradation were considered: growth-associated degradation as a
      carbon and energy source for microbial growth; degradation for maintenance
      energy; and growth-independent degradation. The Haldane modification of the Monod
      equation was used to describe microbial growth rates and to account for possible
      growth inhibition by naphthalene. Multisubstrate interactions were considered and
      described with a noninteractive model for specific growth rates. The sensitivity
      of selected model parameters was analyzed under conditions when naphthalene was
      the sole growth-rate-limiting substrate. The time necessary to achieve a specific
      degree of naphthalene biodegradation was found to be proportional to the initial
      concentration of naphthalene in soil organic matter. The biodegradation rate of
      naphthalene increased when the sorption equilibrium constant of naphthalene was
      reduced. The presence of an alternative carbon source inhibited naphthalene
      biodegradation in spite of the calculated increase in biomass. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18627083
TI  - Separation of enzymes from microorganism crude extracts by free-flow zone
      electrophoresis.
AB  - Continuous, single-step, state-of-the-art preparative separations of enzymes from
      microorganism crude extracts by free-flow zone electrophoresis are presented. In
      the first example, the enzymes formate dehydrogenase, formaldehyde dehydrogenase,
      and methanol oxidase were continuously separated from Candida boidinii crude
      extract. Yields of 85% to 95% and purification factors between 3 and 7 were
      obtained along with a simultaneous separation of the finer cell debris from the
      enzymes. Using multiple injections of sample, a throughput of 46.2 mg protein/h
      was recorded. In the second example, a fivefold purification of beta
      galactosidase from Escherichia coli was achieved along with complete,
      simultaneous cell debris separation from the enzyme. The yield of the enzyme was
      greater than 90%. The preparative free-flow zone electrophoresis experiments were
      run continuously for a period of 12 h and the separations were found to be
      stable; i.e., the enzymes and the cell debris eluted at their respective fraction
      numbers during the entire period. In both examples, choice of the type of buffer
      played a critical role and had to be investigated and optimized experimentally.
      Scale-up aspects of the separations are also discussed. Recently, by comparison
      of free-flow zone electrophoresis with ion-exchange chromatography, we have
      presented evidence that free-flow electrophoresis separations are governed by net
      surface charge (S. Nath et al., Biotechnol. Bioeng. 1993, 42: 829-835). Here, we
      offer further confirmation of this evidence by comparison of preparative free
      flow zone electrophoresis experiments at various pHs on a mixture of two model
      proteins with analytical electrophoretic titration curves of the proteins. We are
      thus in a position to predict separations in free-flow zone electrophoresis. (c)
      1996 John Wiley & Sons, Inc.

PMID- 18627084
TI  - Metabolism of halogenated compounds in the white rot fungus Bjerkandera adusta
      studied by membrane inlet mass spectrometry and tandem mass spectrometry.
AB  - Membrane inlet mass spectrometry has been used for the characterization of
      halogenated organic compounds produced by the fungus Bjerkandera adusta. Using
      this technique we obtained electron impact-, chemical ionization-, electron
      capture negative chemical ionization-mass spectra and tandem mass spectra
      directly from the growth medium. Through this direct analysis of the samples we
      identified novel bioconversion products and confirmed recently published data on
      the production of both chlorinated and brominated methoxybenzaldehyde
      metabolites. Growth profiles of the culture grown on a defined medium showed that
      the production of secondary metabolites starts after approximately 6 days and
      reaches maximal concentrations of 25-250 muM after 15-20 days. Although delayed,
      the production of secondary metabolites paralleled a depletion of glucose from
      the medium and stopped shortly after all glucose had been consumed. Experiments
      in which fluoro- and bromo-labeled 4-methoxybenzaldehydes were added to the
      medium at day 8 showed biotransformation of these compounds into chloro-3-fluoro
      4-methoxy-benzaldehyde and chloro-3-bromo-4-methoxybenzaldehyde, respectively. No
      dichlorinated products were observed, suggesting that halogenation takes place
      only at the meta position on the 4-methoxybenzaldehydes. These experiments are
      the first to bring direct evidence of a halogenation mechanism, where the
      enzymatic attack takes place directly on the 4-methoxybenzaldehyde intermediates.
      (c) John Wiley & Sons, Inc.

PMID- 18627085
TI  - Control of packed column fouling in the continuous fermentation and stripping of
      ethanol.
AB  - By recycling the contents of a 14 L fermentor through a stripping column to
      continuously remove ethanol and reduce product inhibition, continuous complete
      conversion of nutrient feed containing 600 g/L glucose was achieved in a small
      pilot plant. Ethanol was recovered from the carbon dioxide stripping gas in a
      refrigerated condenser, and the gas was reheated with steam and recycled by a
      blower. Productivity of ethanol in the fermentor as high as 15.8 g/L/h and
      condensate production of up to 10 L/day of almost 50% by volume ethanol were
      maintained for up to 60 days of continuous operation. Weekly washing of the
      column packing in situ was required to prevent loss of performance caused by
      attached growth of yeast cells, which restricts the gas flow rate through the
      stripping column. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627086
TI  - Reaction engineering analysis of L-lysine transport by Corynebacterium
      glutamicum.
AB  - To identify potential L-lysine export limitations by Corynebacterium glutamicum
      in the L-lysine production process, the excretion of L-lysine was studied in
      continuous and fed-batch operated stirred tank reactors. A structured biochemical
      model of the L-lysine excretion mechanism was used to determine the activity of
      the export carrier and to calculate a cell-specific concentration of the export
      carrier. For the biochemical characterization of this specific carrier
      concentration a standardized L-lysine efflux test was developed. Carrier
      activity, cell-specific carrier concentration, and the specific L-lysine export
      rate were identified as a function of pH value and L-lysine concentration in the
      reactors. Also, the correlation of these parameters to the metabolic state of C.
      glutamicum was determined. The pH value in the reactor governs the carrier
      activity (maximum at pH 6.5) and the specific carrier concentration (maximum at
      pH 8.0). The specific L-lysine export rate, as the product of carrier activity
      and specific carrier concentration, revealed a maximum at pH 7.0. Decreasing L
      lysine productivities also correlated with decreasing specific carrier
      concentrations. The L-lysine concentration in the reactor had no effect on the
      specific carrier concentration but strongly inhibited the carrier activity. The
      specific export rate was reduced to 50% at 400 mM L-lysine compared to the
      specific export rate at 80 mM L-lysine. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627087
TI  - A flat inclined modular photobioreactor for outdoor mass cultivation of
      photoautotrophs.
AB  - A flat inclined modular photobioreactor (FIMP) for mass cultivation of
      photoautotrophic microorganisms is described. It consists of flat glass reactors
      connected in cascade facing the sun with the proper tilt angles to assure maximal
      exposure to direct beam radiation. The optimal cell density in reference to the
      length of the reactor light path was evaluated, and the effect of the tilt angle
      on utilization of both direct beam as well as diffuse sunlight was quantitatively
      assessed. The mixing mode and extent were also optimized in reference to
      productivity of biomass. The FIMP proved very successful in supporting continuous
      cultures of the tested species of photoautotrophs, addressing the major criteria
      involved in design optimization of photobioreactors: Made of fully transparent
      glass, inclined toward the sun and endowed with a high surface-to-volume ratio,
      it combines an optimal light path with a vigorous agitation system. The maximal
      exposure to the culture to solar irradiance as well as the substantial control of
      temperature facilitate, under these conditions, a particularly high, extremely
      light-limited optimal cell density. The integrated effects of these growth
      conditions resulted in record volumetric and areal output rates of Monodus
      subterraneus, Anabana siamensis, and Spirulina platensis. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18627088
TI  - pH oscillations and constant low pH delay the appearance of highly branched
      (colonial) mutants in chemostat cultures of the quorn(R) myco-protein fungus,
      Fusarium graminearum A3/5.
AB  - At pH 5.8, highly branched (colonial) mutants appear in glucose-limited chemostat
      cultures of Fusarium graminearum A3/5 after ca. 400 h (ca. 107 generations) of
      growth. The appearance of these mutants was delayed by up to 144 h (45
      generations) when the culture was switched at intervals of 120 h between pH 4.8
      and 6.6. The concentration of cycloheximide-resistant macroconidia in the culture
      was used as an indicator of the periodic selection of advantageous mutants and it
      was found that, in chemostat populations subjected to pH oscillations, the
      interval (210 +/- 20 h) between peaks was nearly double that observed in
      chemostat populations cultured at constant pH (124 +/- 12 h at constant pH 5.8
      and 120 h +/- 17 h at constant pH 4.5), indicating that the population evolved
      more slowly under oscillating pH than under constant pH. When grown in mixed
      culture with the parental strain (A3/5), the selective advantage of two colonial
      mutants isolated from chemostat cultures grown under conditions of oscillating pH
      was found to be pH dependent. Compared to cultures grown at constant pH 5.8, a
      delay of ca. 312 h (87 generations) in the appearance of colonial mutants was
      observed when F. graminearum A3/5 was grown in glucose-limited chemostat culture
      at constant pH 4.5. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627089
TI  - Immobilization of Candida cylindracea lipase on colloidal liquid aphrons (CLAs)
      and development of a continuous CLA-membrane reactor.
AB  - A novel technique is described for the immobilization of Candida cylindracea
      lipase in the soapy-shell of colloidal liquid aphrons (CLAs). CLAs consist of a
      micron-sized solvent droplet surrounded by a thin, aqueous, soapy-film and are
      stabilized by a mixture of nonionic and ionic surfactants. Retention of lipase
      within the CLAs is primarily determined by electrostatic interactions between the
      surface charges on the protein and those of the anionic surfactant used (SDS)
      because leakage of the lipase from dispersed CLAs was reduced at low continuous
      phase pH (<pl). Leakage was also reduced after successive dispersions and at
      higher enzyme loading; this latter point suggests that hydrophobic interactions
      became important as the surface area per molecule increases. The activity of both
      free and CLA-immobilized lipase was also determined for the hydrolysis of p
      nitrophenyl acetate and p-nitrophenyl caprylate at various substrate
      concentrations and continuous phase pH. The CLA immobilized lipase displayed a
      broader optimum pH range in both cases and, due to mass transfer limitations, did
      not exhibit a normal Michaelis-Menten dependence on substrate concentration.
      Finally, the possibility of scaling-up this new technique was demonstrated by the
      use of a cross-flow membrane reactor for continuous product separation and
      recycle of the CLA-immobilized enzyme. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627090
TI  - Tyrosinase-containing chitosan gels: A combined catalyst and sorbent for
      selective phenol removal.
AB  - There are a series of examples in which phenols appear as contaminants in process
      streams and their selective removal is required for waste minimization. For the
      selective removal of a phenol from a mixture, we are exploiting the substrate
      specificity of the enzyme tyrosinase to convert phenols into reactive o-quinones
      which are then adsorbed onto the amine-containing polymer chitosan. To
      effectively package the enzyme and sorbent, tyrosinase was immobilized between
      two chitosan gel films. The entrapment of tyrosinase between the films led to
      little loss of activity during immobilization, while tyrosinase leakage during
      incubation was limited. The chitosan gels rapidly adsorb the tyrosinase-generated
      product(s) of phenol oxidation while the capacity of the gels is substantially
      greater than the capacity of chitosan flakes. The performance of tyrosinase
      containing chitosan gels significantly depends on the ratio of tyrosinase-to
      chitosan. High tyrosinase-to-chitosan ratios result in less efficient use of
      tyrosinase, presumably due to suicide inactivation. However, the efficiency of
      chitosan use increases with increased tyrosinase-to-chitosan ratios. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18627091
TI  - Kinetics of phenol biodegradation in the presence of glucose.
AB  - The kinetics of utilization of glucose, phenol, and their mixtures by Pseudomonas
      putida (ATCC 17514) were studied with a continuously aerated, jacketed batch
      reactor operating at 28 degrees C and pH 7.2. It was found that when glucose is
      the sole carbon and energy source, the culture utilizes it following Monod
      kinetics. When phenol is the sole carbon and energy source, the culture
      biodegrades it following Andrews (inhibitory) kinetics. When both glucose and
      phenol are present in the medium, the culture uses them simultaneously but with
      lower specific rates. Reduction of the specific substrate utilization rates
      indicates that the two substances are involved in a cross-inhibitory pattern
      which can be classified as uncompetitive. The values of the kinetic interaction
      constants suggest that glucose inhibits the specific rate of phenol removal much
      more than phenol inhibits the specific rate of glucose utilization. The results
      suggest that substitutable substrates which are dissimilar in origin and
      molecular structure may be involved in an uncompetitive cross-inhibitory
      interaction when they are simultaneously removed. It is also concluded that the
      use of easily degradable substrates may not enhance the per-unit amount of
      biomass removal of compounds which are classified as toxic. A general
      classification of kinetic interactions between substitutable resources is
      proposed. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627092
TI  - The influence of the mode of enzyme preparation on enzymatic enantioselectivity
      in organic solvents and its temperature dependence.
AB  - The enantioselectivities of subtilisin Carlsberg and Rhizomucor miehei lipase in
      organic solvents are found to strongly depend on the method by which the enzymes
      are prepared. For the transesterification between sec-phenethyl alcohol and vinyl
      butyrate in dioxane at 7 degrees C, the enantioselectivity of subtilisin
      precipitated with isopropanol is more than twice that of the enzyme prepared by
      lyophilization from aqueous buffer. Furthermore, the temperature dependence of
      the enantioselectivity is influenced by the mode of enzyme preparation. For
      example, in the aforementioned process the enantioselectivities of subtilisin
      lyophilized from aqueous buffer and crosslinked subtilisin crystals increase when
      the temperature is raised from 7 to 45 degrees C. In contrast, the
      enantioselectivities decrease with temperature for the enzyme precipitated from
      aqueous solution with acetone or isopropanol and for the enzymatic hydrolysis in
      water. The temperature dependence of the enantioselectivity of subtilisin
      lyophilized from buffer is markedly affected by the solvent: In acetonitrile and
      nitromethane the enzyme is more enantioselective at higher temperatures, while
      negligible temperature effects have been found in tetrahydrofuran and pyridine.
      Lyophilized lipase exhibits striking temperature dependencies of its
      enantioselectivity in dioxane, acetonitrile, and nitromethane, while showing
      almost none in pyridine, triethylamine, and tetrahydrofuran. The results
      underscore the importance of the mode of enzyme recovery on enantioselectivity
      and its temperature dependence in enzymatic reactions in organic solvents (in
      contrast to those in water). (c) 1996 John Wiley & Sons, Inc.

PMID- 18627093
TI  - Effects of plasma exposure on cultured hepatocytes: Implications for
      bioartificial liver support.
AB  - In order to examine their potential for use in a bioartificial liver, hepatocytes
      maintained in a collagen sandwich configuration were cultured for 9 days in
      heparinized rat plasma. The cells exhibited a progressive accumulation of
      cytoplasmic lipid droplets which proved to be mainly triglyceride (TG). The rate
      of TG accumulation correlated with the free fatty acid (FFA) content of the
      plasma. Removal of FFA and TG from plasma by ether extraction significantly
      reduced the rate and extent of TG accumulation. A smaller reduction in the rate
      and extent of TG accumulation was observed when cells were maintained in an
      oxygen enriched environment. The lipid accumulation suppressed urea synthesis,
      but clearance of the drug diazepam, although constitutively depressed in plasma,
      appeared unaffected by the accumulation. The functional and morphological effects
      of plasma exposure could be fully reversed after at least 6 days of plasma
      exposure by returning the cells to culture medium.The results indicate that
      elevated FFA in plasma induces lipid accumulation, which inhibits urea synthesis
      in cultured hepatocytes. This suggests that estimates of the cell number needed
      for effective liver support should not be based upon function measurements
      conducted in culture media. Furthermore, optimization of bioartificial liver
      support device use may have to be governed by the need to limit the plasma
      exposure of cultured hepatocytes. However, the highly responsive nature of these
      cultures and the reversibility of the plasma effects suggest that the collagen
      sandwich culture system is a promising foundation for the development of an
      effective bioartificial liver support system. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627094
TI  - Biodegradation of phenol using the self-cycling fermentation (SCF) process.
AB  - Self-cycling fermentation (SCF) in a stirred tank reactor was applied to the
      biodegradation of phenol by Pseudomonas putida. The technique resulted in stable
      and repeatable performance. Complete substrate consumption was achieved under all
      operating conditions investigated. SCF resulted in substrate utilization rates as
      high as 14.5 kg of phenol per cubic meter of fermentor volume per day of
      fermentation, higher than those that have been reported for batch, CSTR, and
      packed column fermentors. A mathematical model of the self-cycling fermentation
      process was expanded to include inhibitory substrate-microorganism combinations,
      and was shown to provide a good fit to both end-of-cycle and intracycle
      experimental data. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627095
TI  - A method for measuring bacterial chemotaxis parameters in a microcapillary.
AB  - A new method was developed which enables chemotaxis parameters to be measured at
      a single-cell level inside a capillary for the first time. The chemotaxis chamber
      consists of two reservoirs communicating through a capillary tube 50 mum in
      diameter. Chemotaxis parameters are measured inside the capillary using image
      analysis, after a nearly linear attractant concentration gradient has been
      generated along the capillary by diffusion. Compared to previously published
      techniques, this method provides a well-characterized chemoattractant
      concentration profile in addition to allowing single-cell parameters to be
      measured inside a fine capillary. This procedure was used to measure the single
      cell chemotaxis parameters for Escherichia coli K12, and the results are compared
      to published data on single E. coli cells chemotaxing in bulk. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18627096
TI  - Removal of chlorophenols from wastewater by immobilized horseradish peroxidase.
AB  - Immobilization of horseradish peroxidase on magnetite and removal of
      chlorophenols using immobilized enzyme were investigated. Immobilization by
      physical adsorption on magnetite was much more effective than that by the
      crosslinking method, and the enzyme was found to be immobilized at 100% of
      retained activity. In addition, it was discovered that horseradish peroxidase was
      selectively adsorbed on magnetite, and the immobilization resulted in a 20-fold
      purification rate for crude enzyme. When immobilized peroxidase was used to treat
      a solution containing various chlorophenols, p-chlorophenol, 2,4-dichlorophenol,
      2,4,5-trichlorophenol, 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol, and
      pentachlorophenol, each chlorophenol was almost 100% removed, and also the
      removal of total organic carbon (TOC) and adsorbable organic halogen (AOX)
      reached more than 90%, respectively. However, in the case of soluble peroxidase,
      complete removal of each chlorophenol could not be attained, and in particular,
      the removal of 2,4,5-trichlorophenol was the lowest, with a removal rate of only
      36%. (c) 1996 John Wiley & Sons, Inc.

PMID- 18627097
TI  - Cardiac expression of the Drosophila Transglutaminase (CG7356) gene is directly
      controlled by myocyte enhancer factor-2.
AB  - The myocyte enhancer factor-2 (MEF2) family of transcription factors plays key
      roles in the activation of muscle structural genes. In Drosophila, MEF2
      accumulates at high levels in the embryonic muscles, where it activates target
      genes throughout the mesoderm. Here, we identify the Transglutaminase gene (Tg;
      CG7356) as a direct transcriptional target of MEF2 in the cardiac musculature. Tg
      is expressed in cells forming the inflow tracts of the dorsal vessel, and we
      identify the enhancer responsible for this expression. The enhancer contains
      three binding sites for MEF2, and can be activated by MEF2 in tissue culture and
      in vivo. Moreover, loss of MEF2 function, or removal of the MEF2 binding sites
      from the enhancer, results in loss of Tg expression. These studies identify a new
      MEF2 target in the cardiac musculature. These studies provide a possible
      mechanism for the activation of transglutaminase genes.

PMID- 18627099
TI  - Gene nomenclature guidelines for the planarian Schmidtea mediterranea.
AB  - We describe a gene nomenclature system for the freshwater planarian Schmidtea
      mediterranea. Guidelines are specified for designating names for genes and
      proteins, as well as for describing RNA-mediated genetic interference (RNAi)
      experiments. The proposed conventions aim to avoid multiple names being ascribed
      to single genes and to establish a uniform, simple method for naming genes in S.
      mediterranea that is readily understood by researchers working on planarians and
      other organisms.

PMID- 18627098
TI  - Xenopus zinc finger transcription factor IA1 (Insm1) expression marks
      anteroventral noradrenergic neuron progenitors in Xenopus embryos.
AB  - The evolutionarily conserved IA1 (Insm1) gene is strongly expressed in the
      developing nervous system. Here, we show that IA1 is expressed during Xenopus
      laevis embryogenesis in neural plate primary neurons as well as in a population
      of uncharacterized anteroventral cells that form in front of the cement gland and
      that we identified as noradrenergic neurons. We also show that the formation of
      those anteroventral cells is dependent on BMPs and inhibited by Notch and that it
      is regulated by the transcription factors Xash1, Phox2, and Hand2. Finally, we
      provide functional evidence suggesting that IA1 may also play a role in their
      formation. Together, our results reveal that IA1 constitutes a novel player
      downstream of Xash1 in the formation of a previously unidentified population of
      Xenopus noradrenergic primary neurons.

PMID- 18627101
TI  - Dependence of computed tomography volume measurements upon section thickness: an
      application to human dry skulls.
AB  - Estimation of intracranial volume (ICV) using computed tomography (CT) scans has
      previously been described. However, we were not able to identify a gold standard
      study that analyzed the effect of section thickness on the estimation of ICV.
      Therefore, we conducted the present study, scanning five dry skulls in the
      coronal and axial planes using a multislice CT machine (Toshiba TSX-101A,
      Aquilion 16 Slice, Tochigi, Japan). Consecutive sections of variable thicknesses
      of 2, 3, 5, 7, and 10 mm, respectively, were used to estimate ICV by means of the
      planimetry method of the Cavalieri principle. All estimations were done by the
      same observer. However, the estimated volumes did not concur with the actual
      volumes of the skulls as determined by the fluid displacement technique (P <
      0.05). In fact, results revealed that the section thicknesses created over- or
      under-projection effects for the estimated volumes. The results were analyzed to
      reveal the deviation principles of the estimates based on section thickness.
      Prediction formulas were calculated to estimate the deviation percentage of the
      ICV depending on section thickness and section plane. Ultimately, the results
      showed that the effect of section thickness on ICV estimates could not be
      overlooked, but that the values obtained could be corrected using the proposed
      prediction formulas presented in this study.

PMID- 18627100
TI  - Enhancer detection in zebrafish permits the identification of neuronal subtypes
      that express Hox4 paralogs.
AB  - Activity of zebrafish hoxb4a in the developing brain was analyzed in comparison
      to hoxa4a and hoxd4a using unique enhancer detection transgenes. Cytoplasmic YFP
      revealed shape and axonal projections of neurons in animals with insertions near
      the Hox4 genes and provided a means for the identification of neuronal subtypes.
      Despite an early activity of the genes in neuroepithelial cells and later in
      immature postmitotic neurons, we found reporter expression in distinct neuronal
      subtypes in the r7-r8-derived hindbrain. Most strikingly, hoxb4a neuronal
      subtypes projected through the vagus and into the pectoral fin while others
      formed symmetrically located fiber tracts innervating the cerebellum and the
      tectum, features that are partially shared by the other two paralogs.
      Collectively, our expression analysis indicates that hoxb4a in combination with
      its paralogs may play a significant role in the development of precerebellar,
      vagal, and pectoral fin neuronal subtypes.

PMID- 18627102
TI  - Unusual termination of the cephalic vein.

PMID- 18627103
TI  - A standardized protocol for needle placement in suboccipital muscles.
AB  - The objective of this study was to assess the safety and accuracy of using common
      anatomic landmarks to guide the placement of needle electrodes into suboccipital
      muscles. Atrophic changes in suboccipital muscles have been reported in some
      patients who have tension-type headaches, and in some patients who have headaches
      resulting from whiplash-type injuries. These atrophic changes most likely result
      from disuse or denervation. Needle electromyography is a definitive technique for
      determining the cause of muscle atrophy, but requires that needle electrodes be
      inserted into the muscle. Suboccipital muscles present a challenge to the
      electromyographer in that they are physically small and are located in close
      proximity to one another. Atrophied muscles with fatty replacement and the
      presence of critical structures such as the vertebral artery further complicate
      the procedure. Using a standardized protocol, three investigators attempted blind
      needle insertions into each of the suboccipital muscles of eight embalmed
      cadavers. A dissector then assessed targeted muscle penetrations, final resting
      positions of the wires, and their proximity to critical structures. Eighty-one
      percent of 181 attempted insertions penetrated the targeted muscles: 83% for the
      rectus capitis posterior minor, 83% for the rectus capitis posterior major, 94%
      for the obliquus capitis superior, and 63% for the obliquus capitis inferior
      muscles, respectively. It was concluded that readily palpable external landmarks
      can be used to safely and reliably guide the insertion of needle electrodes into
      three of the four pairs of suboccipital muscles.

PMID- 18627104
TI  - Three-dimensional study of the musculotendinous architecture of lumbar multifidus
      and its functional implications.
AB  - Lumbar multifidus (LMT) is a key muscle, which provides stability to the lumbar
      spine, and has been shown to have altered neuromuscular recruitment following
      acute episodes of low back pain. Architectural parameters are important
      determinants of function, but have not been well documented for LMT. Therefore,
      the purpose of this study is to model and quantify the architecture of LMT
      throughout its volume. Nine male and one female formalin-embalmed cadaveric
      specimens (average age 80 +/- 11 years) without any evidence of spinal
      deformity/pathology were used. The musculotendinous components of LMT were
      serially dissected and digitized. Next, the data were imported into MAYA to
      create a three-dimensional model of each segment of LMT from which architectural
      parameters including fiber bundle length (FBL), fiber bundle angle (FBA), and
      tendon length were quantified. Water displacement was used to determine volume.
      The data were analyzed using paired t-tests and ANOVA followed by Tukey's post
      hoc test (P <or= 0.05). LMT (L1-L4) has three architecturally distinct regions:
      superficial, intermediate, and deep. Intermediate LMT was absent in all specimens
      at L5. Mean FBL decreased significantly (P <or= 0.05) from superficial (5.8 +/-
      1.6 cm) to deep (2.9 +/- 1.1 cm) as did volume (superficial, 5.6 +/- 2.3 ml;
      deep, 0.7 +/- 0.3 ml) measured at each region. By contrast, mean FBA increased
      from superficial to deep. The current study lends further evidence to support the
      role of different regions within LMT to serve distinct functions particularly to
      produce movement and/or control stability.

PMID- 18627105
TI  - Right accessory phrenic nerve passing through an annulus of the subclavian vein.

PMID- 18627106
TI  - Msx1 and Msx2 are expressed in sub-populations of vascular smooth muscle cells.
AB  - Using an nlacZ reporter gene inserted at the Msx1 and Msx2 loci, we could analyze
      the expression of these homeogenes in the adult mouse. We observed that Msx genes
      are prominently expressed in a subset of blood vessels. The Msx2nlacZ allele is
      mainly expressed in a restricted population of mural cells in peripheral arteries
      and veins. Msx1nlacZ is expressed to a lesser extent by vascular smooth muscle
      cells of peripheral arteries, but is highly expressed in arterioles and
      capillaries, making Msx1 a novel marker for a subpopulation of pericytes.
      Expression is set up early in developing vessels and maintained throughout life.
      In addition, expression of both genes is observed in a few endothelial cells of
      the aorta at fetal stages, and only Msx2 continues to be expressed in this layer
      at the adult stage. These results suggest major functions for Msx genes in
      vascular mural cell formation and remodeling.

PMID- 18627109
TI  - Functional characterization of Lmo2-Cre transgenic zebrafish.
AB  - Cre/loxP system is a powerful tool to manipulate the genome. Transgenic animals
      expressing Cre recombinase in specific tissues or cells have been widely used for
      conditional gene targeting, lineage tracing, and other genetic analyses. In
      zebrafish, the transgenic line with stable expression of Cre in specific tissues
      and cell subtypes has not been generated and its functional activity remains to
      be defined. Here we report the establishment of a stable transgenic fish
      Tg(zlmo2:Cre), which specifically expresses Cre in the primitive hematopoietic
      progenitors and vascular endothelial cells, under the control of lmo2 promoter.
      Our result shows that the Cre expression pattern recapitulates the endogenous
      lmo2 expression pattern during embryogenesis. Crossing of the Tg(zlmo2:Cre) line
      with another established transgenic reporter line Tg(zlmo2:loxP-DsRed-loxP-EGFP),
      induces a robust recombination activity in hematopoietic progenitors and vascular
      endothelial cells. Thus, the Tg(zlmo2:Cre) transgenic line provides an invaluable
      tool to dissect genetic pathways in hematopoietic development and diseases.

PMID- 18627110
TI  - Los Alamos lab suggests HIV spreads faster than thought.

PMID- 18627107
TI  - Notch-regulated oligodendrocyte specification from radial glia in the spinal cord
      of zebrafish embryos.
AB  - During vertebrate neural development, many dividing neuroepithelial precursors
      adopt features of radial glia, which are now known to also serve as neural
      precursors. In mammals, most radial glia do not persist past early postnatal
      stages, whereas zebrafish maintain large numbers of radial glia into adulthood.
      The mechanisms that maintain and specify radial glia for different fates are
      still poorly understood. We investigated formation of radial glia in the spinal
      cord of zebrafish and the role of Notch signaling in their maintenance and
      specification. We found that spinal cord precursors begin to express gfap+, a
      marker of radial glia, during neurogenesis and that gfap cells give rise to both
      neurons and oligodendrocytes. We also determined that Notch signaling is
      continuously required during embryogenesis to maintain radial glia, limit motor
      neuron formation and permit oligodendrocyte development, but that radial glia
      seem to be refractory to changes in Notch activity in postembryonic animals.

PMID- 18627111
TI  - Tanzania to introduce vaccines to tackle childhood pneumonia.

PMID- 18627112
TI  - Call to action against HIV/tuberculosis co-infection.

PMID- 18627113
TI  - UN report urges action towards universal HIV treatment access.

PMID- 18627114
TI  - Predicting global death patterns not an easy task.

PMID- 18627115
TI  - Monoolein-water liquid crystalline gels of gentamicin as bioresorbable implants
      for the local treatment of chronic osteomyelitis: in vitro characterization.
AB  - To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing
      antibiotic systemic toxicity, as well as time and costs of hospitalizations, it
      has been thought that monoolein-water gels incorporating gentamicin sulfate could
      be used as local, bioresorbable,and sustained-release implants. For this purpose,
      four formulations were examined with regard to their physicochemical and in vitro
      drug release characteristics. Hot stage microscopy, differential scanning
      calorimetry (DSC), thermogravimetric analysis (TGA),and X-ray diffraction showed
      cubic liquid crystalline and eutectic structures. The more suitable formulation
      consisting of 80-15-5%wt/wt monoolein-water-gentamicin sulfate progressively
      released the antibiotic for a period of 3 weeks without burst effect. Moreover,
      the content and the release profile of gentamicin sulfate were not significantly
      changed after storage at 2-6 degrees C for a period of 10 months.

PMID- 18627116
TI  - A PET rat model for assessing the effectiveness of new chemotherapies.

PMID- 18627117
TI  - Celecoxib: new indication. Ankylosing spondylitis: no pain justifies the use of a
      cox-2 inhibitor. Patients still exposed to unjustified risks.

PMID- 18627118
TI  - Capecitabine: new indication. Advanced-stage gastric cancer: oral route for some
      patients. Risk of palmoplantar erythrodysaesthesia.

PMID- 18627119
TI  - How to earthquakes come to a halt?

PMID- 18627120
TI  - [Three patients with tuberculous meningitis: treatment started at tentative
      diagnosis].

PMID- 18627121
TI  - Healthcare for London.

PMID- 18627122
TI  - Practice-based commissioning.

PMID- 18627124
TI  - Accidental ecstasy ingestion in a two year old.

PMID- 18627125
TI  - Regulation of cell division by intrinsically unstructured proteins: intrinsic
      flexibility, modularity, and signaling conduits.
AB  - It is now widely recognized that intrinsically unstructured (or disordered)
      proteins (IUPs or IDPs) are found in organisms from all kingdoms of life. In
      eukaryotes, IUPs are highly abundant and perform a wide range of biological
      functions, including regulation and signaling. Despite an increased level of
      interest in understanding the structural biology of IUPs and IDPs, questions
      regarding the mechanisms through which disordered proteins perform their
      biological function(s) remain. In other words, what are the relationships between
      disorder and function for IUPs? There are several excellent reviews that discuss
      the structural properties of IUPs and IDPs since 2005 [Receveur-Brechot, V., et
      al. (2006) Proteins 62, 24-45; Mittag, T., and Forman-Kay, J. D. (2007) Curr.
      Opin. Struct. Biol. 17, 3-14; Dyson, H. J., and Wright, P. E. (2005) Nat. Rev.
      Mol. Cell Biol. 6, 197-208]. Here, we briefly review general concepts pertaining
      to IUPs and then discuss our structural, biophysical, and biochemical studies of
      two IUPs, p21 and p27, which regulate the mammalian cell division cycle by
      inhibiting cyclin-dependent kinases (Cdks). Some segments of these two proteins
      are partially folded in isolation, and they fold further upon binding their
      biological targets. Interestingly, some portions of p27 remain flexible after
      binding to and inhibiting the Cdk2-cyclin A complex. This residual flexibility
      allows otherwise buried tyrosine residues within p27 to be phosphorylated by non
      receptor tyrosine kinases (NRTKs). Tyrosine phosphorylation relieves kinase
      inhibition, triggering Cdk2-mediated phosphorylation of a threonine residue
      within the flexible C-terminus of p27. This, in turn, marks p27 for
      ubiquitination and proteasomal degradation, unleashing full Cdk2 activity which
      drives cell cycle progression. p27, thus, constitutes a conduit for transmission
      of proliferative signals via post-translational modifications. The term "conduit"
      is used here to connote a means of transmission of molecular signals which, in
      the case of p27, correspond to tyrosine and threonine phosphorylation,
      ubiquitination, and, ultimately, proteolytic degradation. Transmission of these
      multiple signals is enabled by the inherent flexibility of p27 which persists
      even after tight binding to the Cdk2-cyclin A complex. Importantly, activation of
      the p27 signaling conduit by oncogenic NRTKs contributes to tumorigenesis in some
      human cancers, including chronic myelogenous leukemia (CML) [Grimmler, M., et al.
      (2007) Cell 128, 269-280] and breast cancer [Chu, I., et al. (2007) Cell 128, 281
      294]. Other IUPs may participate in conceptually similar molecular signaling
      conduits, and dysregulation of these putative conduits may contribute to other
      human diseases. Detailed study of these IUPs, both alone and within functional
      complexes, is required to test these hypotheses and to more fully understand the
      relationships between protein disorder and biological function.

PMID- 18627126
TI  - Conserved discrimination against misacylated tRNAs by two mesophilic elongation
      factor Tu orthologs.
AB  - Elongation factor Tu (EF-Tu) binds and loads elongating aminoacyl-tRNAs (aa
      tRNAs) onto the ribosome for protein biosynthesis. Many bacteria biosynthesize
      Gln-tRNA (Gln) and Asn-tRNA (Asn) by an indirect, two-step pathway that relies on
      the misacylated tRNAs Glu-tRNA (Gln) and Asp-tRNA (Asn) as intermediates.
      Previous thermodynamic and experimental analyses have demonstrated that Thermus
      thermophilus EF-Tu does not bind Asp-tRNA (Asn) and predicted a similar
      discriminatory response against Glu-tRNA (Gln) [Asahara, H., and Uhlenbeck, O.
      (2005) Biochemistry 46, 6194-6200; Roy, H., et al. (2007) Nucleic Acids Res. 35,
      3420-3430]. By discriminating against these misacylated tRNAS, EF-Tu plays a
      direct role in preventing misincorporation of aspartate and glutamate into
      proteins at asparagine and glutamine codons. Here we report the characterization
      of two different mesophilic EF-Tu orthologs, one from Escherichia coli, a
      bacterium that does not utilize either Glu-tRNA (Gln) or Asp-tRNA (Asn), and the
      second from Helicobacter pylori, an organism in which both misacylated tRNAs are
      essential. Both EF-Tu orthologs discriminate against these misacylated tRNAs,
      confirming the prediction that Glu-tRNA (Gln), like Asp-tRNA (Asn), will not form
      a complex with EF-Tu. These results also demonstrate that the capacity of EF-Tu
      to discriminate against both of these aminoacyl-tRNAs is conserved even in
      bacteria like E. coli that do not generate either misacylated tRNA.

PMID- 18627127
TI  - 15N relaxation studies of Apo-Mts1: a dynamic S100 protein.
AB  - Mts1 is a member of the S100 family of EF-hand calcium-binding proteins. Like
      most S100 proteins, Mts1 exists as a dimer in solution and contains one canonical
      and one pseudo-EF-hand motif per monomer, each of which consists of two alpha
      helices connected by a loop capable of coordinating a calcium ion. The backbone
      dynamics of murine apo-Mts1 homodimer have been examined by nuclear magnetic
      resonance spectroscopy. Longitudinal and transverse relaxation data and steady
      state (1)H- (15)N nuclear Overhauser effects were analyzed using model-free
      formalism. The extracted global correlation time is 9.94 ns. Results indicate
      that the protein backbone is most rigid at the dimer interface, made up of
      helices 1 and 4 from each monomer with mean S (2) ( S avg (2)) values
      approximately 0.9, flanked by helices 2 and 3 with lower S avg (2) values of 0.84
      and 0.77, respectively. Each calcium-binding site along with the hinge joining
      the two EF-hands and the N- and C-termini are considerably more flexible than the
      dimer interface on a range of time scales and more flexible than the
      corresponding regions of other S100 proteins studied to date. As the hinge and
      the C-terminal tail are believed to interact with target proteins, these dynamic
      characteristics may have implications for Mts1 activity.

PMID- 18627128
TI  - Arginine coordination in enzymatic phosphoryl transfer: evaluation of the effect
      of Arg166 mutations in Escherichia coli alkaline phosphatase.
AB  - Arginine residues are commonly found in the active sites of enzymes catalyzing
      phosphoryl transfer reactions. Numerous site-directed mutagenesis experiments
      establish the importance of these residues for efficient catalysis, but their
      role in catalysis is not clear. To examine the role of arginine residues in the
      phosphoryl transfer reaction, we have measured the consequences of mutations to
      arginine 166 in Escherichia coli alkaline phosphatase on hydrolysis of ethyl
      phosphate, on individual reaction steps in the hydrolysis of the covalent enzyme
      phosphoryl intermediate, and on thio substitution effects. The results show that
      the role of the arginine side chain extends beyond its positive charge, as the
      Arg166Lys mutant is as compromised in activity as Arg166Ser. Through measurement
      of individual reaction steps, we construct a free energy profile for the
      hydrolysis of the enzyme-phosphate intermediate. This analysis indicates that the
      arginine side chain strengthens binding by approximately 3 kcal/mol and provides
      an additional 1-2 kcal/mol stabilization of the chemical transition state. A 2.1
      A X-ray diffraction structure of Arg166Ser AP is presented, which shows little
      difference in enzyme structure compared to the wild-type enzyme but shows a
      significant reorientation of the bound phosphate. Altogether, these results
      support a model in which the arginine contributes to catalysis through binding
      interactions and through additional transition state stabilization that may arise
      from complementarity of the guanidinum group to the geometry of the trigonal
      bipyramidal transition state.

PMID- 18627129
TI  - Mechanism of the quorum-quenching lactonase (AiiA) from Bacillus thuringiensis.
      1. Product-bound structures.
AB  - Enzymes capable of hydrolyzing N-acyl- l-homoserine lactones (AHLs) used in some
      bacterial quorum-sensing pathways are of considerable interest for their ability
      to block undesirable phenotypes. Most known AHL hydrolases that catalyze ring
      opening (AHL lactonases) are members of the metallo-beta-lactamase enzyme
      superfamily and rely on a dinuclear zinc site for catalysis and stability. Here
      we report the three-dimensional structures of three product complexes formed with
      the AHL lactonase from Bacillus thuringiensis. Structures of the lactonase bound
      with two different concentrations of the ring-opened product of N-hexanoyl- l
      homoserine lactone are determined at 0.95 and 1.4 A resolution and exhibit
      different product configurations. A structure of the ring-opened product of the
      non-natural N-hexanoyl- l-homocysteine thiolactone at 1.3 A resolution is also
      determined. On the basis of these product-bound structures, a substrate-binding
      model is presented that differs from previous proposals. Additionally, the
      proximity of the product to active-site residues and observed changes in protein
      conformation and metal coordination provide insight into the catalytic mechanism
      of this quorum-quenching metalloenzyme.

PMID- 18627130
TI  - Mechanism of the quorum-quenching lactonase (AiiA) from Bacillus thuringiensis.
      2. Substrate modeling and active site mutations.
AB  - The N-acyl- l-homoserine lactone hydrolases (AHL lactonases) have attracted
      considerable attention because of their ability to quench AHL-mediated quorum
      sensing pathways in Gram-negative bacteria and because of their relation to other
      enzymes in the metallo-beta-lactamase superfamily. To elucidate the detailed
      catalytic mechanism of AHL lactonase, mutations are made on residues that
      presumably contribute to substrate binding and catalysis. Steady-state kinetic
      studies are carried out on both the wild-type and mutant enzymes using a spectrum
      of substrates. Two mutations, Y194F and D108N, present significant effects on the
      overall catalysis. On the basis of a high-resolution structural model of the
      enzyme-product complex, a hybrid quantum mechanical/molecular mechanical method
      is used to model the substrate binding orientation and to probe the effect of the
      Y194F mutation. Combining all experimental and computational results, we propose
      a detailed mechanism for the ring-opening hydrolysis of AHL substrates as
      catalyzed by the AHL lactonase from Bacillus thuringiensis. Several features of
      the mechanism that are also found in related enzymes are discussed and may help
      to define an evolutionary thread that connects the hydrolytic enzymes of this
      mechanistically diverse superfamily.

PMID- 18627131
TI  - Further insight into the mechanism of stereoselective proton abstraction by
      bacterial copper amine oxidase.
AB  - During the catalytic reaction of copper amine oxidase, one of the two prochiral
      hydrogen atoms at the C1 position of substrate amine is stereoselectively
      abstracted by a conserved Asp residue serving as a general base. Using
      stereospecifically deuterium-labeled enantiomers of 2-phenylethylamine, we
      previously showed that the pro-S alpha-proton is abstracted by the enzyme from
      Arthrobacter globiformis (AGAO) [Uchida, M., et al. (2003) Biosci. Biotechnol.
      Biochem. 67, 2664-2667]. More recently, we have also demonstrated that the pro-S
      selectivity of alpha-proton abstraction is fully retained even in the reaction of
      a mutant AGAO lacking the catalytic base [Chiu, Y.-C., et al. (2006) Biochemistry
      45, 4105-4120]. On the basis of these findings, we have proposed that the
      stereoselectivity of alpha-proton abstraction is primarily determined by the
      conformation of the Schiff base intermediate formed between the substrate and the
      topa quinone cofactor (TPQ), stabilized by the binding of the distal part of the
      substrate to a hydrophobic pocket of the enzyme. In this conformation, the pro-S
      hydrogen atom to be abstracted is nearly perpendicular to the plane of the Schiff
      base-TPQ conjugate system, achieving the maximum overlap of sigma- and pi
      orbitals. To further elucidate the stereochemical details, we have synthesized
      stereospecifically deuterium-labeled enantiomers of ethylamine, a very poor
      substrate for AGAO, in addition to those structurally related to the preferred
      substrate, 2-phenylethylamine. In marked contrast to the nearly complete pro-S
      selectivity of alpha-proton abstraction for most substrates that have been
      examined, the stereoselectivity for ethylamine decreased significantly to as
      little as 88%. The crystal structure of AGAO soaked with ethylamine showed very
      poor electron densities for the substrate Schiff base intermediate, showing that
      its conformation is not defined uniquely. Thus, the stereoselectivity of alpha
      proton abstraction during the copper amine oxidase reaction is closely associated
      with the conformational flexibility of the substrate Schiff base intermediate.

PMID- 18627132
TI  - Kinetic analyses of retaining endo-(xylo)glucanases from plant and microbial
      sources using new chromogenic xylogluco-oligosaccharide aryl glycosides.
AB  - A library of phenyl beta-glycosides of xylogluco-oligosaccharides was synthesized
      via a chemoenzymatic approach to produce new, specific substrates for
      xyloglucanases. Tamarind xyloglucan was completely hydrolyzed to four, variably
      galactosylated component oligosaccharides based on Glc 4 backbones, using a
      Trichoderma endo-glucanase mixture. Oligosaccharide complexity could be further
      reduced by beta-galactosidase treament. Subsequent per- O-acetylation, alpha
      bromination, phase-transfer glycosylation, and Zemplen deprotection yielded
      phenyl glycosides of XXXG and XLLG oligosaccharides with a broad range of aglycon
      p K a values. Kinetic and product analysis of the action of the archetypal plant
      endo-xyloglucanase, Tropaeolum majus NXG1, on these compounds indicated that
      formation of the glycosyl-enzyme intermediate was rate-limiting in the case of
      phenol leaving groups with p K a values of >7, leading exclusively to substrate
      hydrolysis. Conversely, substrates with aglycon p K a values of 5.4 gave rise to
      a significant amount of transglycosylation products, indicating a change in the
      relative rates of formation and breakdown of the glycosyl-enzyme intermediate for
      these faster substrates. Notably, comparison of the initial rates of XXXG-Ar and
      XLLG-Ar conversion indicated that catalysis by TmNXG1 was essentially insensitive
      to the presence of galactose in the negative subsites for all leaving groups.
      More broadly, analysis of a selection of enzymes from CAZy families GH 5, 12, and
      16 indicated that the phenyl glycosides are substrates for anomeric configuration
      retaining endo-xyloglucanases but are not substrates for strict xyloglucan endo
      transglycosylases (XETs). The relative activities of the GH 5, 12, and 16 endo
      xyloglucanases toward GGGG-CNP, XXXG-CNP, and XLLG-CNP reflected those observed
      using analogous high molar mass polysaccharides. These new chromogenic substrates
      may thus find wide application in the discovery, screening, and detailed kinetic
      analysis of new xyloglucan-active enzymes.

PMID- 18627133
TI  - Development of an ion mobility quadrupole time of flight mass spectrometer.
AB  - We describe here a new ion mobility capable mass spectrometer which comprises a
      drift cell for mobility separation and a quadrapole time of flight mass
      spectrometer for mass analysis--the MoQTOF. A commercial QToF instrument
      (Micromass UK Ltd., Manchester, UK) has been modified by the inclusion of an
      additional chamber containing a drift cell and ancillary ion optics. The drift
      cell is 5.1 cm long made from a copper block and is mounted from a top hat flange
      in a chamber situated post source optics and prior to the quadapole analyzer.
      Details of this instrument are provided along with information about how it can
      be used to acquire mobilities of ions along with their mass to charge ratios. The
      MoQTOF is used to examine conformations of a series of antimicrobial peptides
      based on a beta-defensin template. In vivo, these cationic cystine-rich
      amphiphilic peptides are conformationally restrained by three or more disulfide
      bridges, although recent findings by several groups have cast doubt on the
      importance of canonical disulfide pairing to antimicrobial activities. By
      synthesizing a panel of variants to Defb14 (the murine orthologue of HBD3), we
      exploit ion mobility to distinguish conformational differences which arise due to
      disulfide formation and to the hydrophobicity of the peptide sequence. Our gas
      phase results are interpreted in terms of the antimicrobial and chemotacic
      properties of beta-defensins, and this mass spectrometry based approach to
      discern structure may have a role in future design of novel antibiotics.

PMID- 18627134
TI  - Electrochemical DNAzyme sensor for lead based on amplification of DNA-Au bio-bar
      codes.
AB  - An electrochemical DNAzyme sensor for sensitive and selective detection of lead
      ion (Pb(2+)) has been developed, taking advantage of catalytic reactions of a
      DNAzyme upon its binding to Pb(2+) and the use of DNA-Au bio-bar codes to achieve
      signal enhancement. A specific DNAzyme for Pb(2+) is immobilized onto an Au
      electrode surface via a thiol-Au interaction. The DNAzyme hybridizes to a
      specially designed complementary substrate strand that has an overhang, which in
      turn hybridizes to the DNA-Au bio-bar code (short oligonucleotides attached to 13
      nm gold nanoparticles). A redox mediator, Ru(NH3)6(3+), which can bind to the
      anionic phosphate of DNA through electrostatic interactions, serves as the
      electrochemical signal transducer. Upon binding of Pb(2+) to the DNAzyme, the
      DNAzyme catalyzes the hydrolytic cleavage of the substrate, resulting in the
      removal of the substrate strand along with the DNA bio-bar code and the bound
      Ru(NH3)6(3+) from the Au electrode surface. The release of Ru(NH3)6(3+) results
      in lower electrochemical signal of Ru(NH3)6(3+) confined on the electrode
      surface. Differential pulse voltammetry (DPV) signals of Ru(NH3)6(3+) provides
      quantitative measures of the concentrations of Pb(2+), with a linear calibration
      ranging from 5 nM to 0.1 microM. Because each nanoparticle carries a large number
      of DNA strands that bind to the signal transducer molecule Ru(NH3)6(3+), the use
      of DNA-Au bio-bar codes enhances the detection sensitivity by five times,
      enabling the detection of Pb(2+) at a very low level (1 nM). The DPV signal
      response of the DNAzyme sensor is negligible for other divalent metal ions,
      indicating that the sensor is highly selective for Pb(2+). Although this DNAzyme
      sensor is demonstrated for the detection of Pb(2+), it has the potential to serve
      as a general platform for design sensors for other small molecules and heavy
      metal ions.

PMID- 18627135
TI  - Novel thermoresponsive nonviral gene vector: P(NIPAAm-co-NDAPM)-b-PEI with
      adjustable gene transfection efficiency.
AB  - A thermoresponsive cationic copolymer, poly( N-isopropylacrylamide- co- N-(3
      (dimethylamino)propyl)methacrylamide)- b-polyethyleneimine (P(NIPAAm- co-NDAPM)-
      b-PEI), was designed and synthesized as a potential nonviral gene vector. The
      lower critical solution temperature (LCST) of P(NIPAAm- co-NDAPM)- b-PEI in water
      measured by UV-vis spectroscopy was 38 degrees C. P(NIPAAm- co-NDAPM)- b-PEI as
      the gene vector was evaluated in terms of cytotoxicity, buffer capability
      determined by acid-base titration, DNA binding capability characterized by
      agarose gel electrophoresis and particle size analysis, and in vitro gene
      transfection. P(NIPAAm- co-NDAPM)- b-PEI copolymer exhibited lower cytotoxicity
      in comparison with 25 kDa PEI. Gel retardation assay study indicated that the
      copolymer was able to bind DNA completely at N/P ratios higher than 30. At 27
      degrees C, the mean particle sizes of P(NIPAAm- co-NDAPM)- b-PEI/DNA complexes
      decreased from 1200 to 570 nm corresponding to the increase in N/P ratios from 10
      to 60. When the temperature changed to 37 degrees C, the mean particle sizes of
      complexes decreased from 850 to 450 nm correspondingly within the same N/P ratio
      range due to the collapse of thermoresponsive PNIPAAm segments. It was found that
      the transfection efficiency of P(NIPAAm- co-NDAPM)- b-PEI/DNA complexes was
      higher than or comparable to that of 25 kDa PEI/DNA complexes at their optimal
      N/P ratios. Importantly, the transfection efficiency of P(NIPAAm- co-NDAPM)- b
      PEI/DNA complexes could be adjusted by altering the transfection and cell culture
      temperature.

PMID- 18627136
TI  - Continuum electrostatics for electronic structure calculations in bulk amorphous
      polymers: application to polylactide.
AB  - The bond rotational energy landscapes of polylactide (PLA) oligomers were
      estimated using electron density functional theory (DFT) at the B3LYP/6-31G**
      level, both in vacuo and with a self-consistent reaction field (SCRF) method to
      simulate the electronic environment within the condensed phase. The SCRF method
      was evaluated for application to polymeric systems, and we demonstrate the
      difficulties involved in applying the method to bulk amorphous polymers with
      specific attention to the selection of the solvent probe radius. In addition,
      rotational isomeric states (RIS) calculations were performed, showing the effect
      of accounting for the bulk phase reaction field on the bond rotational energetics
      and characteristic ratio. We conclude that present methods of accounting for bulk
      environments in electronic structure calculations are not well suited for use
      with polymeric systems, and the development of improved methods is needed in this
      area.

PMID- 18627137
TI  - Bond multiplicity in transition-metal complexes: applications of two-electron
      valence indices.
AB  - In the present study the applicability of the bond multiplicities from the
      Nalewajski and Mrozek valence indices was demonstrated for a variety of
      transition metal-based systems. The Nalewajski-Mrozek valence indices and bond
      multiplicity indices have been implemented in the Amsterdam Density Functional
      program. Selected examples comprise the carbonyl complexes (selected tetra- and
      hexacarbonyls, binary monocarbonyls of the first-row transition metals),
      phosphines, the ligands' trans-influence, as well as multiple metal-ligand and
      metal-metal bonds. The results show that the calculated bond multiplicity indices
      correspond well to experimental predictions based on bond lengths and vibrational
      frequencies for all discussed classes of complexes. Almost perfect linear
      correlation between the bond indices and vibrational frequencies was observed for
      carbonyls and the oxo complexes; the calculated bond multiplicity reproduces the
      accepted order for the trans-influence of different ligands, rationalizes
      unusually low vibrational freqencies in the [OsO 3N] (-)complex compared to other
      nitrido complexes, explains the geometrical asymmetry in the MoO 3 solid, and
      confirms the multiple character of the metal-metal bond in the [Re 2Cl 8] (2-)
      complex. Thus, the Nalewajski and Mrozek method can be successfully used as a
      supplementary analysis tool for electronic structure for studies involving
      transition metal complexes.

PMID- 18627138
TI  - Homodimerization of neurotensin 1 receptor involves helices 1, 2, and 4: insights
      from quaternary structure predictions and dimerization free energy estimations.
AB  - A computational approach based upon rigid-body docking, ad hoc filtering, and
      cluster analysis has been combined with a protocol for dimerization free energy
      estimations to predict likely interfaces in the neurotensin 1 receptor (NTS1)
      homodimers. The results of this study suggest that the likely intermonomer
      interfaces compatible with in vitro binding affinity constants essentially
      involve helices 1, 2, and 4 and do not include disulfide bridges. The correlative
      model initially developed on Glycophorin A and herein extended to a G protein
      Coupled Receptor (GPCR) appears to be a useful tool for estimating the
      association free energies of transmembrane proteins independent of the size and
      shape of the interface. In the desirable future cases, in which in vitro
      intermonomer binding affinities will be available for other GPCRs, such a
      correlative model will work as an additional criterion for helping in the
      selection of the most likely dimers.

PMID- 18627139
TI  - Synthesis and structure of an aluminum borate chloride consisting of 12-membered
      borate rings and aluminate clusters.
AB  - A new aluminum borate chloride (PKU-8) was synthesized in a flux of boric acid,
      and the structure was established using powder X-ray diffraction techniques. PKU
      8 contains an unusual framework structure of a large cage consisting of 12
      membered borate rings [B 12O 30] and aluminate octahedra clusters [Al 7O 24].

PMID- 18627140
TI  - Cobalt(II) citrate cubane single-molecule magnet.
AB  - An investigation of the magnetic properties of the cobalt(II) citrate cubane
      [C(NH 2) 3] 8{Co 4(cit) 4}.4H 2O reveals that the cluster is a new cobalt(II)
      single-molecule magnet, with an energy barrier to reorientation of the
      magnetization, Delta E/ k B = 21 K, and tau 0 = 8 x 10 (-7) s. The compound
      displays distinct, frequency-dependent peaks in the out-of-phase (chi'')
      component of the ac magnetic susceptibility and magnetization versus field
      hysteresis loops that are temperature and sweep rate dependent. The hysteresis
      loops collapse at zero field due to very fast quantum tunneling of the
      magnetization (QTM).

PMID- 18627141
TI  - Oxoperoxo vanadium(V) complexes of L-lactic acid: density functional theory study
      of structure and NMR chemical shifts.
AB  - Various combinations of density functionals and pseudopotentials with associated
      valence basis-sets are compared for reproducing the known solid-state structure
      of [V 2O 2(OO) 2 l-lact 2] (2-) cis . Gas-phase optimizations at the B3LYP/SBKJC
      level have been found to provide a structure that is close to that seen in the
      solid state by X-ray diffraction. Although this may result in part from error
      compensation, this optimized structure allowed satisfactory reproduction of
      solution multinuclear NMR chemical shifts of the complex in all-electron DFT-IGLO
      calculations (UDFT-IGLO-PW91 level), suggesting that it is probably close to that
      found in solution. This combination of approaches has subsequently been used to
      optimize the structures of the vanadium oxoperoxo complexes [V 2O 3(OO) l-lact 2]
      (2-) cis , [V 2O 3(OO) l-lact 2] (2-) trans , and [VO(OO)( l-lact)(H 2O)] (-) cis
      . The (1)H, (13)C, (51)V, and (17)O NMR chemical shifts for these complexes have
      been calculated and compared with the experimental solution chemical shifts.
      Excellent agreement is seen with the (13)C chemical shifts, while somewhat
      inferior agreement is found for (1)H shifts. The (51)V and (17)O chemical shifts
      of the dioxo vanadium centers are well reproduced, with differences between
      theoretical and experimental shifts ranging from 22.9 to 35.6 ppm and from 25.1
      to 43.7 ppm, respectively. Inferior agreement is found for oxoperoxo vanadium
      centers, with differences varying from 137.3 to 175.0 ppm for (51)V shifts and
      from 148.7 to 167.0 ppm for (17)O(oxo) shifts. The larger errors are likely to be
      due to overestimated peroxo O-O distances. The chosen methodology is able to
      predict and analyze a number of interesting structural features for vanadium(V)
      oxoperoxocomplexes of alpha-hydroxycarboxylic acids.

PMID- 18627144
TI  - Direct electrodeposition of Cu2Sb for lithium-ion battery anodes.
AB  - We describe the direct single potential electrodeposition of crystalline Cu2Sb, a
      promising anode material for lithium-ion batteries, from aqueous solutions at
      room temperature. The use of citric acid as a complexing agent increases the
      solubility of antimony salts and shifts the reduction potentials of copper and
      antimony toward each other, enabling the direct deposition of the intermetallic
      compound at pH 6. Electrodeposition of Cu2Sb directly onto conducting substrates
      represents a facile synthetic method for the synthesis of high quality samples
      with excellent electrical contact to a substrate, which is critical for further
      battery testing.

PMID- 18627145
TI  - Design and use of organic nanoparticles prepared from star-shaped polymers with
      reactive end groups.
AB  - Star-shaped poly(isobornyl acrylate) (PiBA) was prepared by atom transfer radical
      polymerization (ATRP) using multifunctional initiators. The optimal ATRP
      conditions were determined to minimize star-star coupling and to preserve high
      end group functionality (>90%). Star-shaped PiBA with a narrow polydispersity
      index was synthesized with 4, 6, and 12 arms and of varying molecular weight
      (10,000 to 100,000 g x mol(-1)) using 4 equiv of a Cu(I)Br/PMDETA catalyst system
      in acetone. Matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) analysis, NMR spectroscopy, and size exclusion chromatography (SEC)
      confirmed their controlled synthesis. The bromine end group of each arm was then
      transformed to a reactive end group by a nucleophilic substitution with
      methacrylic acid or cinnamic acid (conversion >90%). These reactive star polymers
      were used to prepare PiBA nanoparticles by intramolecular polymerization of the
      end groups. The successful preparation of this new type of organic nanoparticles
      on a multigram scale was proven by NMR spectroscopy and SEC. Subsequently, they
      have been used as additives for linear, rubbery poly(n-butyl acrylate). Rheology
      measurements indicated that the viscoelastic properties of the resulting
      materials can be fine-tuned by changing the amount of incorporated nanoparticles
      (1-20 wt %), as a result of the entanglements between the nanoparticles and the
      linear polymers.

PMID- 18627146
TI  - Air-assisted high-performance field-effect transistor with thin films of picene.
AB  - A field-effect transistor (FET) with thin films of picene has been fabricated on
      SiO2 gate dielectric. The FET showed p-channel enhancement-type FET
      characteristics with the field-effect mobility, mu, of 1.1 cm2 V-1 s-1 and the on
      off ratio of >10(5). This excellent device performance was realized under
      atmospheric conditions. The mu increased with an increase in temperature, and the
      FET performance was improved by exposure to air or O2 for a long time. This
      result implies that this device is an air (O2)-assisted FET. The FET
      characteristics are discussed on the basis of structural topography and the
      energy diagram of picene thin films.

PMID- 18627147
TI  - Multifunctional nanostructures based on inorganic nanoparticles and
      oligothiophenes and their exploitation for cellular studies.
AB  - The combination of materials that possess different properties (such as, for
      instance, fluorescence and magnetism) into one single object of nanoscale size
      represents an attractive challenge for biotechnology, especially for their
      potential relevance in biomedical applications. We report here the preparation of
      novel bifunctional conjugates based on the linkage of inorganic nanoparticles to
      organic oligothiophene fluorophores (OTFs). In comparison to the organic dyes
      commonly used in bioimaging and more similarly to colloidal quantum dots, OTFs
      have broad optical absorption spectra, and therefore OTF fluorophores emitting at
      different colors can be excited with a single excitation source, allowing for
      easier multiplexing analysis. In this work we show the preparation of OTF
      nanoparticle conjugates based on gold and iron oxide nanoparticles and their
      characterization using different techniques such as gel electrophoresis,
      photoluminescence spectroscopy, dynamic light scattering, and so on. In addition,
      by performing an in vitro study on human tumor cells we show that OTF
      nanoparticle conjugates emitting at different colors can be used for multiplexing
      detection. Also, in the case of iron oxide-OTF conjugates, once uptaken by the
      cells, we show that they preserve both their fluorescent and their magnetic
      properties.

PMID- 18627148
TI  - Concise synthesis of spirocyclic, bridged gamma-butyrolactones via
      stereospecific, dyotropic rearrangements of beta-lactones involving 1,2-acyl and
      delta-lactone migrations.
AB  - Dyotropic processes involving unprecedented 1,2-acyl migrations provide access to
      novel spirocyclic, bridged keto-gamma-lactones from a series of fused, tricyclic
      beta-lactones, available via biscyclization of ketoacids including a new
      asymmetric variant. In addition, a spirocyclic bis-gamma-lactone was generated
      via a dyotropic process involving a 1,2-beta-lactone/sigma-lactone interchange.
      Overall, this sequence provides a simple, two-step process for conversion of
      diketoacids to complex spiro[5.n]alkanes bearing a contiguous tertiary carbon
      center, a quaternary carbon center, and a tertiary alcohol in the form of a
      bridging gamma-lactone.

PMID- 18627149
TI  - Modeling of graphite oxide.
AB  - Based on density functional calculations, optimized structures of graphite oxide
      are found for various coverages by oxygen and hydroxyl groups, as well as their
      ratio corresponding to the minimum of total energy. The model proposed describes
      well-known experimental results. In particular, it explains why it is so
      difficult to reduce the graphite oxide up to pure graphene. Evolution of the
      electronic structure of graphite oxide with the coverage change is investigated.

PMID- 18627150
TI  - Exceptional behavior over the whole adsorption-storage-delivery cycle for NO in
      porous metal organic frameworks.
AB  - Two porous metal organic frameworks (MOFs), [M2(C8H2O6)(H2O)2] x 8 H2O (M = Co,
      Ni), perform exceptionally well for the adsorption, storage, and water-triggered
      delivery of the biologically important gas nitric oxide. Adsorption and powder X
      ray diffraction studies indicate that each coordinatively unsaturated metal atom
      in the structure coordinates to one NO molecule. All of the stored gas is
      available for delivery even after the material has been stored for several
      months. The combination of extremely high adsorption capacity (approximately 7
      mmol of NO/g of MOF) and good storage stability is ideal for the preparation of
      NO storage solids. However, most important is that the entire reservoir of stored
      gas is recoverable on contact with a simple trigger (moisture). The activity of
      the NO storage materials is proved in myography experiments showing that the NO
      releasing MOFs cause relaxation of porcine arterial tissue.

PMID- 18627152
TI  - Molecular basis of DNA photodimerization: intrinsic production of cyclobutane
      cytosine dimers.
AB  - Based on CASPT2 results, the present contribution establishes for the first time
      that cytosine photodimer formation (C< >C) is mediated along the triplet and
      singlet manifold by a singlet-triplet crossing, (T1/S0)X, and by a conical
      intersection, (S1/S0)CI, respectively. The former can be accessed in a
      barrierless way from a great variety of photochemical avenues and exhibits a
      covalent single bond between the ethene C6-C6' carbon atoms of each monomer. The
      efficiency of the stepwise triplet mechanism, however, would be modulated by the
      effectiveness of the intersystem crossing mechanism. The results provide the
      grounds for the understanding of the potential photogenotoxicity of endogenous
      and exogenous compounds via triplet-triplet sensitization, with a lower bound for
      cytosine oligonucleotides predicted to be 2.70 eV, and give support to the
      traditional view of the primary role of triplet excited states in the
      photochemistry of DNA, a well-known source of photoproducts in solution under
      triplet photosensitization conditions. The function played by singlet excimers
      (excited dimers) to explain both the red-shifted fluorescence and photoreaction
      is highlighted. A rationale on the pronounced wavelength dependence of the
      observed fluorescence is offered. Geometrical arrangements at the time of light
      irradiation close to, but energetically above, (S1/S0)CI are suggested as
      reactive orientations that become prone to produce C< >C directly, with no energy
      barrier. Because of the outstanding intrinsic ability of cytosine to form stable
      relaxed excimers, the system located near the bound relaxed excimer has to
      accumulate enough vibrational energy to surmount a small barrier of 0.2 eV to
      reach (S1/S0)CI, making the overall process to proceed at a slower relative rate
      as compared to other compounds such as thymine, which is not susceptible of
      forming so stable excimers.

PMID- 18627153
TI  - Atomic force microscopy studies of DNA-wrapped carbon nanotube structure and
      binding to quantum dots.
AB  - Single-stranded DNA is an effective noncovalent dispersant for individual single
      walled carbon nanotubes (CNTs) in aqueous solution, forming a CNT-DNA hybrid
      material that has advantages for CNT separations and applications. Atomic force
      microscopy (AFM) reveals a regular pattern on the surface of CNT-DNA. We found
      this pattern to be independent of the length and sequence of the wrapping DNA,
      yet different from the structures observed for CNTs dispersed with sodium dodecyl
      sulfate in the absence of DNA. We wrapped CNTs with thiol-modified DNA to form
      stable conjugates of CNT-DNA and core/shell CdSe/ZnS quantum dots; AFM imaging of
      these conjugates identified for the first time the location of DNA on the CNT-DNA
      nanomaterial. Our results suggest that the AFM pattern of CNT-DNA is formed by
      helical turns (approximately 14-nm pitch) of wrapped DNA strands that are closely
      arranged end-to-end in a single layer along the CNT. This work demonstrates the
      useful functionalization of CNTs with quantum dots in a manner that avoids
      direct, destructive modification of the CNT surface and suggests nearly complete
      surface coverage of the nanotubes with DNA.

PMID- 18627154
TI  - Opposed steric constraints in human DNA polymerase beta and E. coli DNA
      polymerase I.
AB  - DNA polymerase selectivity is crucial for the survival of any living species, yet
      varies significantly among different DNA polymerases. Errors within DNA
      polymerase-catalyzed DNA synthesis result from the insertion of noncanonical
      nucleotides and extension of misaligned DNA substrates. The substrate binding
      characteristics among DNA polymerases are believed to vary in properties such as
      shape and tightness of the binding pocket, which might account for the observed
      differences in fidelity. Here, we employed 4'-alkylated nucleotides and primer
      strands bearing 4'-alkylated nucleotides at the 3'-terminal position as steric
      probes to investigate differential active site properties of human DNA polymerase
      beta (Pol beta) and the 3'-->5'-exonuclease-deficient Klenow fragment of E. coli
      DNA polymerase I (KF(exo-)). Transient kinetic measurements indicate that both
      enzymes vary significantly in active site tightness at both positions. While
      small 4'-methyl and -ethyl modifications of the nucleoside triphosphate perturb
      Pol beta catalysis, extension of modified primer strands is only marginally
      affected. Just the opposite was observed for KF(exo-). Here, incorporation of the
      modified nucleotides is only slightly reduced, whereas size augmentation of the
      3'-terminal nucleotide in the primer reduces the catalytic efficiency by more
      than 7000- and 260,000-fold, respectively. NMR studies support the notion that
      the observed effects derive from enzyme substrate interactions rather than
      inherent properties of the modified substrates. These findings are consistent
      with the observed differential capability of the investigated DNA polymerases in
      fidelity such as processing misaligned DNA substrates. The results presented
      provide direct evidence for the involvement of varied steric effects among
      different DNA polymerases on their fidelity.

PMID- 18627155
TI  - Supramolecular architectures of beta-cyclodextrin-modified chitosan and pyrene
      derivatives mediated by carbon nanotubes and their DNA condensation.
AB  - Beta-cyclodextrin-modified chitosan 1 was synthesized via the Schiff base
      reaction between 6-O-(4-formylphenyl)-beta-cyclodextrin and chitosan (CHIT), and
      then the supramolecular dyad assemblies 2 and 3 were respectively fabricated from
      the subunit 1 through the inclusion of adamantane-modified pyrene into the beta
      cyclodextrin cavity and the wrapping of a CHIT chain on multiwalled carbon
      nanotubes (MWCNTs). The water-soluble dyad 3 further interacted with adamantane
      modified pyrene, forming a stable triad assembly 4. They were extensively
      characterized by NMR, thermogravimetric analysis, UV-vis, Raman spectroscopy, X
      ray photoelectron spectroscopy, transmission electron microscopy, and atomic
      force microscopy (AFM). Furthermore, the DNA condensation abilities of 1-4 were
      validated by AFM and dynamic light scattering, which indicates that the DNA
      condensing capability of CHIT can be pronouncedly improved by either the pyrene
      grafts or the MWCNT medium. The cooperation between cationic and aromatic groups
      as well as the dispersion of CHIT agglomerates by MWCNTs are the key factors to
      enhance DNA condensation of cationic polymers.

PMID- 18627156
TI  - The carbon-skeleton rearrangement in tropane alkaloid biosynthesis.
AB  - High-level quantum chemistry calculations have been performed to examine the
      carbon-skeleton rearrangement of the tropane alkaloid littorine to hyoscyamine.
      Two pathways involving radical and carbocation intermediates have been
      investigated in this regard, namely, stepwise (or fragmentation-recombination)
      and concerted. The fragmentation products are calculated to be of high energy for
      both the radical- and carbocation-based mechanisms (136.3 and 170.9 kJ mol(-1),
      respectively). Similarly, the rearrangement barrier for the radical-based
      concerted pathway is calculated to be quite high (135.6 kJ mol(-1)). In contrast,
      the carbocation-based concerted pathway is found to be associated with a
      relatively low barrier (47.4 kJ mol(-1)). The ionization energy of the substrate
      derived radical 3a is calculated to be 7.01 eV, suggesting that its oxidation to
      generate the substrate-derived carbocation 3b ought to be facile. In an attempt
      to investigate how an enzyme might modulate the rearrangement barriers, the
      separate and combined influences of partially protonating the migrating group and
      partially deprotonating the spectator OH group of the substrate were
      investigated. Such interactions can lead to significant reductions in the
      rearrangement barrier for both the radical- and carbocation-based concerted
      pathways, although the carbocation pathway continues to have significantly lower
      energy requirements. Also, the relatively high (gas-phase) acidity of the OH
      group of the product-related carbocation 4b indicates that the direct formation
      of hyoscyamine aldehyde (6) is a highly exothermic process. Although we would not
      wish to rule out alternative possibilities, our calculations suggest that a
      concerted rearrangement mechanism involving carbocations constitutes a viable low
      energy pathway for the carbon-skeleton rearrangement in tropane alkaloid
      biosynthesis.

PMID- 18627158
TI  - Evidence from mechanistic probes for distinct hydroperoxide rearrangement
      mechanisms in the intradiol and extradiol catechol dioxygenases.
AB  - Three mechanistic probes were used to investigate whether the Criegee
      rearrangement step of catechol 1,2-dioxygenase (CatA) from Acinetobacter sp.
      proceeds via a direct 1,2-acyl migration, via homolytic O-O cleavage, or via a
      benzene oxide-oxepin rearrangement. Incubation of CatA with 3-chloroperoxybenzoic
      acid led to the formation of a 9:1 mixture of 2-chlorophenol and 3-chlorophenol,
      via a mechanism involving O-O homolytic cleavage. Incubation of CatA with 2
      hydroperoxy-2-methylcyclohexanone led to formation of 5,6-diketoheptan-1-ol, also
      consistent with an O-O homolytic cleavage mechanism, and not consistent with a
      direct 1,2-acyl migration. No reaction product was isolated from incubation of
      CatA with 6-hydroxymethyl-6-methylcyclohexa-2,4-dienone, an analogue that is able
      to undergo the benzene oxide-oxepin rearrangement, but not able to undergo O-O
      homolytic cleavage. In contrast, incubation of extradiol dioxygenase MhpB from
      Escherichia coli with 6-hydroxymethyl-6-methylcyclohexa-2,4-dienone led to the
      formation of a 2-tropolone ring expansion product, consistent with a direct 1,2
      alkenyl migration for extradiol cleavage. Taken together, the results imply
      different mechanisms for the Criegee rearrangement steps of intradiol and
      extradiol catechol dioxygenases: a direct 1,2-alkenyl migration for extradiol
      cleavage and an O-O homolytic cleavage mechanism for intradiol cleavage.

PMID- 18627159
TI  - G-quadruplex DNA assemblies: loop length, cation identity, and multimer
      formation.
AB  - G-rich DNA sequences are able to fold into structures called G-quadruplexes. To
      obtain general trends in the influence of loop length on the structure and
      stability of G-quadruplex structures, we studied oligodeoxynucleotides with
      random bases in the loops. Sequences studied are dGGGW(i)GGGW(j)GGGW(k)GGG, with
      W = thymine or adenine with equal probability, and i, j, and k comprised between
      1 and 4. All were studied by circular dichroism, native gel electrophoresis, UV
      monitored thermal denaturation, and electrospray mass spectrometry, in the
      presence of 150 mM potassium, sodium, or ammonium cations. Parallel conformations
      are favored by sequences with short loops, but we also found that sequences with
      short loops form very stable multimeric quadruplexes, even at low strand
      concentration. Mass spectrometry reveals the formation of dimers and trimers.
      When the loop length increases, preferred quadruplex conformations tend to be
      more intramolecular and antiparallel. The nature of the cation also has an
      influence on the adopted structures, with K(+) inducing more parallel multimers
      than NH4(+) and Na(+). Structural possibilities are discussed for the new
      quadruplex higher-order assemblies.

PMID- 18627160
TI  - Design and synthesis of ladder-shaped tetracyclic, heptacyclic, and decacyclic
      ethers and evaluation of the interaction with transmembrane proteins.
AB  - Ladder-shaped polyether (LSP) toxins represented by brevetoxins and ciguatoxins
      are thought to bind to transmembrane (TM) proteins. To elucidate the interactions
      of LSPs with TM proteins, we have synthesized artificial ladder-shaped polyethers
      (ALPs) containing 6/7/6/6 tetracyclic, 6/7/6/6/7/6/6 heptacyclic, and
      6/7/6/6/7/6/6/7/6/6 decacyclic systems, based on the convergent method via alpha
      cyano ethers. The ALPs possessing the simple iterative structure with different
      numbers of rings would be useful for structure-activity relationship studies on
      the molecular length, which is supposed to be important when naturally occurring
      LSPs elicit their toxicity. Two series of ALPs were prepared to evaluate the
      hydrophilic or hydrophobic effects of the side chains: (i) both sides were
      functionalized as diols (A series), and (ii) one side remained as diol and the
      other side was protected as benzyl ethers (B series). To examine the interaction
      of these ALPs with TM proteins, dissociation of glycophorin A (GpA) dimers into
      monomers was evaluated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The heptacyclic ether (ALP7B) elicited the most potent activity
      in the presence of 2% SDS buffer, whereas the decacyclic ether (ALP10A) exhibited
      an intriguing phenomenon to induce precipitation of GpA in a dose-dependent
      manner, under the low concentration of SDS (0.03%). ALP10A also induced
      precipitation of integrin alpha 1beta 1, a TM protein known to form heterodimers
      in the lipid bilayer membranes. The different activities among the ALPs can be
      accounted for by the concept of "hydrophobic matching" that is, lengths of the
      hydrophobic region including the side chains of ALP7B and ALP10A are ca. 25 A,
      which match the lengths of the hydrophobic region of alpha-helical TM proteins,
      as well as the hydrophobic thickness of lipid bilayer membranes. The concept of
      the hydrophobic matching would be a clue to understanding the interaction between
      LSPs and TM proteins, and also a guiding principle to design ALPs possessing
      potent affinities with TM proteins.

PMID- 18627161
TI  - New cinnamon-based active paper packaging against Rhizopusstolonifer food
      spoilage.
AB  - A new active paper package based on the incorporation of cinnamon essential oil
      to solid wax paraffin as an active coating is proposed, developed, and evaluated.
      The antifungal activity of the active paper is tested against Rhizopusstolonifer,
      and the results demonstrate that 6% (w/w) of the essential oil in the active
      coating formulation completely inhibits the growth of R. stolonifer, whereas 4%
      still has strong antimicrobial activity in in vitro conditions. Then, active
      paper is evaluated with actual food, sliced bread, using different storage times.
      After 3 days of storage, almost complete inhibition is obtained with 6% cinnamon
      essential oil. Qualitative analysis by solid-phase microextraction and
      determination of cinnamaldehyde in the sliced bread were also performed and
      confirmed the strong correspondence between the inhibition of the mold and the
      amount of cinnamaldehyde in the bread.

PMID- 18627162
TI  - Geographical characterization of polyfloral and acacia honeys by nuclear magnetic
      resonance and chemometrics.
AB  - The importance of geographical origin determination is an increasing and pressing
      requirement for all foods. Honey is one of the largest studied foods due to its
      nutritional and medicinal properties in a correct diet. In this paper, a total of
      41 honey samples (polyfloral and acacia) from different countries have been
      analyzed in terms of (1)H NMR spectroscopy coupled with multivariate statistical
      methods. Unsupervised principal component analysis resulted as an efficient tool
      in distinguishing (1)H NMR spectra of polyfloral and acacia honey samples and for
      geographical characterization of the latter ones. Hierarchical projection to
      latent structures discriminant analysis was successfully applied for the
      discrimination among polyfloral honey samples of different geographical origins.
      (13)C NMR spectroscopy was applied to honey samples with the aim to investigate
      possible sugar isoforms differentiation. Our preliminary data indicated a
      different isoforms ratio between betaFP and betaFF only for polyfloral
      Argentinean samples, while Hungarian samples showed resonance shifts for some
      carbons of alphaFF, betaFP, betaFF, and alphaGP isoforms for both varieties.
      These data confirmed the potentiality of (13)C spectroscopy in food
      characterization, especially in sugar-based foods.

PMID- 18627163
TI  - Optimization of fabrication parameters to produce chitosan-tripolyphosphate
      nanoparticles for delivery of tea catechins.
AB  - This work investigated the polyanion-initiated gelation process in fabricating
      chitosan-tripolyphosphate (CS-TPP) nanoparticles intended to be used as carriers
      for delivering tea catechins. The results demonstrated that the particle size and
      surface charge of CS-TPP nanoparticles could be controlled by fabrication
      conditions. For preparation of CS-TPP nanoparticles loaded with tea catechins,
      the effects of modulating conditions including contact time between CS and tea
      catechins, CS molecular mass, CS concentration, CS-TPP mass ratio, initial pH
      value of CS solution, and concentration of tea catechins on encapsulation
      efficiency and the release profile of tea catechins in vitro were examined
      systematically. The study found that the encapsulation efficiency of tea
      catechins in CS-TPP nanoparticles ranged from 24 to 53%. In addition, FT-IR
      analysis showed that the covalent bonding and hydrogen bonding between tea
      catechins and CS occurred during the formation of CS-TPP nanoparticles loaded
      with tea catechins. Furthermore, studies on the release profile of tea catechins
      in vitro demonstrated that the controlled release of tea catechins using CS-TPP
      nanoparticles was achievable.

PMID- 18627164
TI  - Kinetic characterization of O-phospho-L-tyrosine phosphohydrolase activity of two
      fungal phytases.
AB  - Fungal phytases belonging to "histidine acid phosphatase" or HAP class of
      phosphohydrolases that catalyze the hydrolysis of phytic acid could also
      hydrolyze O-phospho-L-tyrosine, which is also called phosphotyrosine. Two
      phytases from Aspergillus niger and Aspergillus awamori with pH optima 2.5 were
      tested for phosphotyrosine hydrolase activity; both enzymes cleaved the
      phosphomonoester bond of phosphotyrosine efficiently at acidic pH. The Km for
      phosphotyrosine ranged from 465 to 590 microM as opposed to 135 to 160 microM for
      phytate. The Vmax, however, is 2-4 times higher for phosphotyrosine than it is
      for phytate. The catalytic efficiency of phytase for phosphotyrosine is on the
      same order as it is for phytate (3.5 x 10(6) to 1.6 x 10(7) M(-1) s(-1)); the pH
      versus activity profile for phosphotyrosine is, however, different from what it
      is for phytate. The temperature optima shifted 5 degrees C higher to 70 degrees C
      when phosphotyrosine was used as the substrate. Taken together, the kinetic data
      show that fungal HAPs that are known as PhyB are capable of cleaving the
      phosphomonoester bond in phosphotyrosine. This is the first time that
      phosphotyrosine phosphatase (PTPase) activity has been reported for the subgroup
      of HAP known as phytase.

PMID- 18627165
TI  - Influence of different dietary doses of n-3- or n-6-rich vegetable fats and alpha
      tocopheryl acetate supplementation on raw and cooked rabbit meat composition and
      oxidative stability.
AB  - This study evaluates the effects of replacing beef tallow added to rabbit feeds
      (3% w/w) by different doses (0%, 1.5% and 3% w/w) of n-6- or n-3-rich vegetable
      fat sources (sunflower and linseed oil, respectively) and alpha-tocopheryl
      acetate supplementation (0 and 100 mg/kg) on the fatty acid composition, alpha
      tocopherol content, and oxidation levels [assessed by analyzing thiobarbituric
      acid (TBA) and lipid hydroperoxide values] in rabbit meat. We also measured these
      parameters after cooking and refrigerated storage of cooked rabbit meat. Both
      dietary alpha-tocopheryl acetate supplementation and the dose and source of fat
      added to feeds influenced meat fatty acid composition, modifying the n-6/n-3
      ratio, which was more nutritionally favorable when linseed oil was used.
      Furthermore, the addition of linseed oil and the supplementation with alpha
      tocopheryl acetate enhanced long-chain PUFA biosynthesis. However, the addition
      of 3% linseed oil increased meat oxidation, and although it was reduced by
      dietary supplementation with alpha-tocopheryl acetate in raw meat, this reduction
      was not as effective after cooking. Therefore, dietary supplementation with 1.5%
      linseed oil plus 1.5% beef tallow and with alpha-tocopheryl acetate would be
      recommended to improve the nutritional quality of rabbit meat.

PMID- 18627166
TI  - Differences in odor-active compounds of trincadeira wines obtained from five
      different clones.
AB  - Odorant compounds of five young clonal red wines made from cv. Trincadeira, a
      native grape variety of Vitis vinifera L. grown in Portugal, were studied using
      2001 and 2003 vintages. The study was carried out using gas chromatography-mass
      spectrometry (GC-MS) for compound identification and the gas chromatography
      olfactometry (GC-O) posterior intensity method to detect the potentially most
      important aroma compounds. Forty-one odorant peaks were detected by GC-O
      analysis, from which 31 were identified by GC-MS. The odorant compounds with the
      highest odorant average intensities are 3-methylbutanoic acid, 2-phenylethanol,
      2,5-dimethyl-4-hydroxy-3(2H)-furanone, and 4-vinylguaiacol. The GC-O analysis
      showed odor intensity differences among compounds, which was confirmed by
      analysis of variance (ANOVA). Principal component analysis (PCA) and hierarchical
      cluster analysis (HCA) showed that the five clonal wines from the 2001 vintage
      were more similar than those from the 2003 vintage. Moreover, stepwise linear
      discriminant analysis (SLDA) demonstrated that the factor vintage has influence
      on the Trincadeira clonal red wine odorant profile differentiation.

PMID- 18627167
TI  - Synthesis of angiotensin I-converting enzyme (ACE)-inhibitory peptides and gamma
      aminobutyric acid (GABA) during sourdough fermentation by selected lactic acid
      bacteria.
AB  - This article aimed at investigating the synthesis of angiotensin I-converting
      enzyme (ACE)-inhibitory peptides and gamma-aminobutyric acid (GABA) during
      sourdough fermentation of white wheat, wholemeal wheat, and rye flours. Sourdough
      lactic acid bacteria, selected previously for proteinase and peptidase activities
      toward wheat proteins or for the capacity of synthesizing GABA, were used. The
      highest ACE-inhibitory activity was found by fermenting flour under semiliquid
      conditions (dough yield 330) and, especially, by using wholemeal wheat flour.
      Fourteen peptides, not previously reported as ACE-inhibitory, were identified
      from the water/salt-soluble extract of wholemeal wheat sourdough (IC 50 0.19-0.54
      mg/mL). The major part of the identified peptides contained the well-known
      antihypertensive epitope VAP. The synthesis of GABA increased when the dough
      yield was decreased to 160. The highest synthesis of GABA (258.71 mg/kg) was
      found in wholemeal wheat sourdough.

PMID- 18627168
TI  - Structure and functional properties of sorghum starches differing in amylose
      content.
AB  - Starches were isolated from grains of waxy, heterowaxy, and normal sorghum. To
      study the relationship between starch structure and functionality and guide
      applications of these starches, amylose content, amylopectin chain-length
      distributions, gelatinization and retrogradation, pasting properties, dynamic
      rheological properties, and in vitro enzyme digestion of raw starches were
      analyzed. Heterowaxy sorghum starch had intermediate amylose content, pasting
      properties, and dynamic rheological properties. Stress relaxation was a useful
      indicator of cooked starch cohesiveness. Cooked heterowaxy sorghum starch (10%
      solids) had a viscoelastic-solid type of character, whereas cooked waxy sorghum
      starch behaved like a viscoelastic liquid. Amylopectin of normal sorghum starch
      had a slightly higher proportion of chains with degree of polymerization (DP) of
      6-15 (45.5%) compared with amylopectin of heterowaxy starch (44.1%), which had a
      gelatinization peak temperature 2 degrees C higher than normal sorghum starch.
      Heterowaxy sorghum starch contained significantly lower rapidly digestible starch
      (RDS) and higher resistant starch (RS) than waxy sorghum starch.

PMID- 18627169
TI  - Model approach to starch functionality in bread making.
AB  - We used modified wheat starches in gluten-starch flour models to study the role
      of starch in bread making. Incorporation of hydroxypropylated starch in the
      recipe reduced loaf volume and initial crumb firmness and increased crumb gas
      cell size. Firming rate and firmness after storage increased for loaves
      containing the least hydroxypropylated starch. Inclusion of cross-linked starch
      had little effect on loaf volume or crumb structure but increased crumb firmness.
      The firming rate was mostly similar to that of control samples. Presumably, the
      moment and extent of starch gelatinization and the concomitant water migration
      influence the structure formation during baking. Initial bread firmness seems
      determined by the rigidity of the gelatinized granules and leached amylose.
      Amylopectin retrogradation and strengthening of a long-range network by
      intensifying the inter- and intramolecular starch-starch and possibly also starch
      gluten interactions (presumably because of water incorporation in retrograded
      amylopectin crystallites) play an important role in firming.

PMID- 18627170
TI  - HRMS directly from TLC slides. A powerful tool for rapid analysis of organic
      mixtures.
AB  - High-resolution mass spectra (HRMS) of individual spots on thin-layer
      chromatography (TLC) slides can now be obtained quickly and easily at atmospheric
      pressure, with zero sample preparation, using commercially available
      instrumentation. The method is complementary to GC-mass spectrometry but is not
      limited to compounds of high volatility and high thermal stability. TLC-HRMS can
      be used to monitor chemical reactions in real time and has the capacity thereby
      to accelerate significantly the pace of synthetic organic chemistry.

PMID- 18627171
TI  - Controllable highly stereoselective reaction of in situ generated magnesium
      dienolate intermediates with different electrophiles.
AB  - In this paper, we have described an efficient controllable stereoselective alpha
      acylation and -allylation reaction of the magnesium dienolate intermediates
      generated in situ from the Fe(III)-catalyzed reaction between 2,3-allenoates and
      Grignard reagents with different electrophiles to afford 2-acylated or allylated
      3( Z)- or ( E)-alkenoates depending on the nature of the electrophiles and
      reaction conditions. The distinct stereoselectivity may be caused by the
      isomerization of metallic Z-1,3-dienoate to E-1,3-dienoate via the intermediacy
      of anti-allylic MgCl and syn-metallic species.

PMID- 18627172
TI  - Gold-catalyzed cycloisomerization of N-Propargylindole-2-carboxamides:
      application toward the synthesis of lavendamycin analogues.
AB  - A series of N-propargylindole-2-carboxamides were found to undergo a AuCl 3
      catalyzed cycloisomerization to give beta-carbolinones in high yield. The
      corresponding beta-chlorocarboline derivative was prepared and used for Pd(0)
      catalyzed cross-coupling chemistry directed toward the synthesis of lavendamycin
      analogues.

PMID- 18627173
TI  - CD and MCD studies of the effects of component B variant binding on the biferrous
      active site of methane monooxygenase.
AB  - The multicomponent soluble form of methane monooxygenase (sMMO) catalyzes the
      oxidation of methane through the activation of O 2 at a nonheme biferrous center
      in the hydroxylase component, MMOH. Reactivity is limited without binding of the
      sMMO effector protein, MMOB. Past studies show that mutations of specific MMOB
      surface residues cause large changes in the rates of individual steps in the MMOH
      reaction cycle. To define the structural and mechanistic bases for these
      observations, CD, MCD, and VTVH MCD spectroscopies coupled with ligand-field (LF)
      calculations are used to elucidate changes occurring near and at the MMOH
      biferrous cluster upon binding of MMOB and the MMOB variants. Perturbations to
      both the CD and MCD are observed upon binding wild-type MMOB and the MMOB variant
      that similarly increases O 2 reactivity. MMOB variants that do not greatly
      increase O 2 reactivity fail to cause one or both of these changes. LF
      calculations indicate that reorientation of the terminal glutamate on Fe2
      reproduces the spectral perturbations in MCD. Although this structural change
      allows O 2 to bridge the diiron site and shifts the redox active orbitals for
      good overlap, it is not sufficient for enhanced O 2 reactivity of the enzyme.
      Binding of the T111Y-MMOB variant to MMOH induces the MCD, but not CD changes,
      and causes only a small increase in reactivity. Thus, both the geometric
      rearrangement at Fe2 (observed in MCD) coupled with a more global conformational
      change that may control O 2 access (probed by CD), induced by MMOB binding, are
      critical factors in the reactivity of sMMO.

PMID- 18627174
TI  - Allosteric coupling in pyruvate dehydrogenase kinase 2.
AB  - Mitochondrial pyruvate dehydrogenase kinase 2 (PDHK2) phosphorylates the pyruvate
      dehydrogenase multienzyme complex (PDC) and thereby controls the rate of
      oxidative decarboxylation of pyruvate. The activity of PDHK2 is regulated by a
      variety of metabolites such as pyruvate, NAD (+), NADH, CoA, and acetyl-CoA. The
      inhibitory effect of pyruvate occurs through the unique binding site, which is
      specific for pyruvate and its synthetic analogue dichloroacetate (DCA). The
      effects of NAD (+), NADH, CoA, and acetyl-CoA are mediated by the binding site
      that recognizes the inner lipoyl-bearing domain (L2) of the dihydrolipoyl
      transacetylase (E2). Both allosteric sites are separated from the active site of
      PDHK2 by more than 20 A. Here we show that mutations of three amino acid residues
      located in the vicinity of the active site of PDHK2 (R250, T302, and Y320) make
      the kinase resistant to the inhibitory effect of DCA, thereby uncoupling the
      active site from the allosteric site. In addition, we provide evidence that
      substitutions of R250 and T302 can partially or completely uncouple the L2
      binding site. Based on the available structural data, R250, T302, and Y320
      stabilize the "open" and "closed" conformations of the built-in lid that controls
      the access of a nucleotide into the nucleotide-binding cavity. This strongly
      suggests that the mobility of ATP lid is central to the allosteric regulation of
      PDHK2 activity serving as a conformational switch required for communication
      between the active site and allosteric sites in the kinase molecule.

PMID- 18627175
TI  - Structural analysis of substrate and effector binding in Mycobacterium
      tuberculosis D-3-phosphoglycerate dehydrogenase.
AB  - The crystal structure of Mycobacterium tuberculosis d-3-phosphoglycerate
      dehydrogenase has been solved with bound effector, l-serine, and substrate,
      hydroxypyruvic acid phosphate, at resolutions of 2.7 and 2.4 A, respectively. The
      subunits display the same extreme asymmetry as seen in the apo-structure and
      provide insight into the mode of serine binding and closure of the active site.
      Mutagenesis studies confirm the identity of the main residues involved in serine
      binding and suggest that the poly glycine stretch in the loop that contains the
      locus for the 160 degrees rotation that leads to subunit asymmetry may have a
      larger role in folding than in catalysis. The lack of electron density for the
      cofactor, NADH, in any of the crystals examined led us to study binding by
      stopped flow kinetic analysis. The kinetic data suggest that productive NADH
      binding, that would support catalytic turnover, is dependent on the presence of
      substrate. This observation, along with the binding of substrate in the active
      site, but in an unproductive conformation, suggests a possible mechanism where
      initial binding of substrate leads to enhanced interaction with cofactor
      accompanied by a rearrangement of catalytically critical residue side chains.
      Furthermore, comparison to the structure of a truncated form of human d-3
      phosphoglycerate dehydrogenase with cofactor and a substrate analog, provides
      insight into the conformational changes that occur during catalysis.

PMID- 18627176
TI  - Depolarization of surface-enhanced fluorescence: an approach to fluorescence
      polarization assays.
AB  - Localized surface plasmons of metallic particles of subwavelength sizes strongly
      modify the spectral properties of nearby fluorophores. The enhanced radiative
      decay rate leads to high fluorescence efficiencies and decreased fluorescence
      lifetimes. In this report we show that metal-enhanced fluorescence generated by
      the presence of the silver islands on the glass substrate displays high
      depolarization. Intensities, lifetimes, and emission anisotropies of several
      fluorophore protein conjugates have been studied in the absence and presence of
      metallic nanostructures. Despite highly decreased lifetimes of about 10-fold and
      immobilization of conjugates on the solid substrate, the observed emission
      anisotropies for all fluorophores on the metal-enhanced substrate decreased 300
      500% compared to that in solution. This observation implies a new generation of
      fluorescence polarization immunoassays with broad applications because of no
      restrictions to the lifetime of the probe and the size of labeled biomolecules.
      The changes in polarization are due to binding that occur on the bioactive
      surface localized near the metal particles.

PMID- 18627177
TI  - 100,000-fold concentration of anions in capillary zone electrophoresis using
      electroosmotic flow controlled counterflow isotachophoretic stacking under field
      amplified conditions.
AB  - An electroosmotic flow (EOF) controlled counterflow isotachophoretic stacking
      boundary (cf-ITPSB) system under field amplified conditions has been examined as
      a way to improve the sensitivity of anions separated by capillary zone
      electrophoresis. The system comprised a high concentration of a high-mobility
      leading ion (100 mM chloride) and a low concentration of low-mobility terminating
      ion (1-3 mM MES or CHES) added to the sample in an unmodified fused-silica
      capillary at pH 8.05, buffered with Tris. Computer simulation studies using the
      software GENTRANS showed an increase in sensitivity of at least 10-fold over the
      previous cf-ITPSB system for simple inorganic ions, nitrite and nitrate. The
      simulations also suggested that the cf-ITPSB became stationary within the
      capillary and that its stationary position was not adversely affected by the
      concentration of MES. This was in contrast to experimental results that showed a
      slow and continual movement of the cf-ITPSB. This was more pronounced at lower
      concentrations of terminator (i.e., <3 mM) and resulted in a loss of resolution
      due to the cf-ITPSB being closer to the detector upon separation. This
      discrepancy was attributed to the change in pH across the capillary due to
      electrolysis and low buffering capacity in the sample, a phenomenon that cannot
      be simulated by the GENTRANS software. Replacement of MES with CHES as a lower
      mobility ion with increased buffer capacity failed to reduce the movement of the
      cf-ITPSB but did provide a further 3-fold improvement in sensitivity. The
      potential of this approach for sensitivity enhancement was demonstrated for the
      co-EOF separation of a mixture of six inorganic and small organic ions, with
      detection limits at the single-figure nanogram per liter level. These detection
      limits are 100,000 times better than can be achieved by normal hydrodynamic
      injection (ions prepared in water) and 250 times better than has been achieved by
      other online preconcentration approaches. The application of the EOF-controlled
      cf-ITPSB with counter-EOF separation of two pharmaceutical pollutants, naproxen
      and diflunisal, was also demonstrated with an improvement in sensitivity of 1000
      giving detection limits of 350 ng/L in sewage treatment wastewater without any
      offline pretreatment.

PMID- 18627178
TI  - Microprocessing of liquid plugs for bio/chemical analyses.
AB  - A microfluidic device and operation to handle liquid plugs for biochemical
      analyses were developed for efficient handling of plugs of many solutions. A
      major part of the device was a T-junction consisting of a main flow channel and a
      handling flow channel. Unit operations including attachment of plugs, division of
      a plug, sorting of plugs, and formation of plugs of various lengths enabled
      controlled sequential reactions in a microflow channel. Rapid mixing could easily
      be achieved by moving a plug formed by merging two plugs back and forth. The
      device could be used for efficient characterization of performance in
      bio/chemical sensing. In experiments using L-glutamate oxidase, plugs containing
      an enzyme or a substrate were formed, mixed sequentially, and the intensity of
      fluorescence from plugs of different concentrations of L-glutamate or pHs could
      be measured simultaneously. Cross-contamination of plugs by neighboring plugs
      poses a problem in using the same flow channel repeatedly. However, the influence
      could be minimized by using a cleansing plug placed between them in a
      sufficiently hydrophobic flow channel and by processing the plugs at a low
      velocity. The device can be a critical component for microprocessing in various
      bio/chemical analyses.

PMID- 18627179
TI  - Atomic force microscopy study of the effect of pulsed electric field on
      Staphylococcus epidermidis.
AB  - The effect of a pulsed electric field (PEF) on Staphylococcus epidermidis was
      investigated by using an atomic force microscopy (AFM) image and force
      measurement under liquid. The changes in the bacterial envelope were probed in
      situ before and after applying different dosages of PEF. Our results indicated
      that PEF induced the changes of bacterial peptidoglycan layer and the exposure of
      plasma membrane. This conclusion was further confirmed by two control
      experiments: the effect of the lysozyme or heat on the bacterial envelope.
      Furthermore, our results demonstrated that AFM analysis including image and force
      measurement is helpful to explain the relationship between the chemical
      composition change of the cellular envelope and the external stimulation.

PMID- 18627180
TI  - XCMS2: processing tandem mass spectrometry data for metabolite identification and
      structural characterization.
AB  - Mass spectrometry based metabolomics represents a new area for bioinformatics
      technology development. While the computational tools currently available such as
      XCMS statistically assess and rank LC-MS features, they do not provide
      information about their structural identity. XCMS(2) is an open source software
      package which has been developed to automatically search tandem mass spectrometry
      (MS/MS) data against high quality experimental MS/MS data from known metabolites
      contained in a reference library (METLIN). Scoring of hits is based on a "shared
      peak count" method that identifies masses of fragment ions shared between the
      analytical and reference MS/MS spectra. Another functional component of XCMS(2)
      is the capability of providing structural information for unknown metabolites,
      which are not in the METLIN database. This "similarity search" algorithm has been
      developed to detect possible structural motifs in the unknown metabolite which
      may produce characteristic fragment ions and neutral losses to related reference
      compounds contained in METLIN, even if the precursor masses are not the same.

PMID- 18627181
TI  - Dimensions of a free linear polymer and polymer immobilized on silica
      nanoparticles of a zwitterionic polymer in aqueous solutions with various ionic
      strengths.
AB  - The dimensions and intermolecular interactions of a surface-grafted and unbound
      free polyampholyte, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), were
      estimated in aqueous solutions with various ionic strengths. Free linear PMPC was
      synthesized by atom-transfer radical polymerization (ATRP), and static light
      scattering (SLS) and dynamic light scattering (DLS) were carried out for the PMPC
      solutions with various concentrations of NaCl, c s. The hydrodynamic radius R H
      and the second virial coefficient A 2 of PMPC were independent of c s (0-0.5 M),
      though both R H and A 2 of polyampholytes usually strongly depend on the ionic
      strength. PMPC-immobilized silica nanoparticles (PMPC-SiNP) were also synthesized
      by surface-initiated ATRP, and DLS was carried out as for the solutions of linear
      PMPC to investigate the dependence of the dimensions of PMPC immobilized on a
      solid surface on the ionic strength. The molecular weight and surface density of
      PMPC immobilized on SiNP were estimated from the results obtained by GPC, NMR,
      and thermogravimetric analysis. The independence of R H of PMPC-SiNP was also
      observed, but its magnitude was larger than that of linear PMPC, although the
      molecular weight of PMPC immobilized on SiNP was smaller than that of linear
      PMPC. The larger dimension of PMPC immobilized on SiNP was explained by the
      excluded volume effect between the immobilized polymer chains.

PMID- 18627182
TI  - Site-specific dense immobilization of antibody fragments on polymer brushes
      supported by silicone nanofilaments.
AB  - For site-specific dense immobilization of antibodies on a solid support, we
      prepared phosphorylcholine copolymer brushes on silicone nanofilaments. The
      nanofilaments were prepared on a silicon wafer by treatment with
      trichloromethylsilane (MeSiCl 3). To generate Si-OH groups on the nanofilaments,
      O 2 plasma was irradiated on the surface. Initiators for atom transfer radical
      polymerization (ATRP) were then coupled on the filaments. Phosphorylcholine
      copolymer brushes were prepared by a "grafting from" process, and pyridyl
      disulfide groups were introduced into the polymer chains. F(ab') fragments were
      then specifically immobilized onto these surfaces via a thiol-disulfide
      interchange reaction. The amount of antibodies immobilized on the nanofilament
      supported copolymer brushes was approximately 65 times greater than that on
      smooth wafer-supported copolymer brushes.

PMID- 18627183
TI  - Quantitatively modeling the equilibrium properties of thiol-decorated gold
      nanoparticles.
AB  - We employ a molecular mean-field theory to quantitatively understand the sizes,
      surfactant surface coverage, and size fluctuations of gold nanocrystals decorated
      with thiol surfactants of different chain lengths. Our model assumes that
      surfactant-coated nanoparticles are equilibrium structures. We find that packing
      constraints experienced by the surfactant tails are less significant for more
      curved (smaller) particles. This effect enables us to rationalize the
      experimental observations/deductions that the thiol coverage per unit area
      increases with decreasing particle size. The reduction of surface coverage with
      increasing size also explains the fact that size polydispersity increases with
      increasing nanoparticle size. We find that increasing the length of the
      surfactants results in larger nanoparticles.

PMID- 18627185
TI  - Structural and textural evolution during folding of layers of layered double
      hydroxides.
AB  - Layers of a layered double hydroxide, containing aluminum 4-fold coordinated,
      were partially folded in order to obtain a fibrous hydrotalcite-like compound.
      The hydrotalcite layers, in the presence of an anionic surfactant (sodium dodecyl
      sulfate) after hydrothermal treatment for 2 weeks, acquire a mesoporous-like
      arrangement. The transformation was monitored by techniques sensitive to
      structural and textural properties. Results suggest that brucite-like layers can
      be joined throughout unsaturated coordinated aluminum, that is, tetrahedral
      aluminum which links through hydrogen bonds to form aluminum octahedrally
      coordinated. The fractal dimension parameter was very sensitive to evolution from
      layered to fibrous hydrotalcites.

PMID- 18627184
TI  - Microfluidic lithography of SAMs on gold to create dynamic surfaces for directed
      cell migration and contiguous cell cocultures.
AB  - A straightforward, flexible, and inexpensive method to create patterned self
      assembled monolayers (SAMs) on gold using microfluidics-microfluidic lithography
      has been developed. Using a microfluidic cassette, alkanethiols were rapidly
      patterned on gold surfaces to generate monolayers and mixed monolayers. The
      patterning methodology is flexible and, by controlling the solvent conditions and
      thiol concentration, permeation of alkanethiols into the surrounding PDMS
      microfluidic cassette can be advantageously used to create different patterned
      feature sizes and to generate well-defined SAM surface gradients with a single
      microfluidic chip. To demonstrate the utility of microfluidic lithography,
      multiple cell experiments were conducted. By patterning cell adhesive regions in
      an inert background, a combination of selective masking of the surface and
      centrifugation achieved spatial and temporal control of patterned cells, enabling
      the design of both dynamic surfaces for directed cell migration and contiguous
      cocultures. Cellular division and motility resulted in directed, dynamic
      migration, while the centrifugation-aided seeding of a second cell line produced
      contiguous cocultures with multiple sites for heterogeneous cell-cell
      interactions.

PMID- 18627186
TI  - Preparation of oriented titanium phosphate and tin phosphate/polyaniline hybrid
      films by electrochemical deposition.
AB  - The preparation of hybrid films of metal (Ti and Sn) phosphate nanosheets and
      polyaniline by simultaneous electrophoretic and electrolytic deposition was
      performed in an acetonitrile solvent. Emeraldine polyaniline was intercalated
      between the phosphate nanosheets with a monolayer arrangement. The obtained
      hybrid films were several tens of micrometers in thickness. The ratio of
      incorporated polyaniline to metal phosphate in the hybrid films reaches to around
      0.45 and 0.30 at suitable concentrations of tetrabutylammonium hydroxide (TBAOH).
      These amounts correspond with occupancy of polyaniline in the interlayer gallery
      of several tens percent. Fractions of voids in a horizontal direction were around
      22 and 1% in titanium phosphate/polyaniline and tin phosphate/polyaniline hybrid
      films, respectively. Thus, anodic electrodeposition makes it possible to form
      thick films of intercalation compounds of alpha-titanium and tin phosphates with
      polyaniline. These hybrid films were examined for redox activity. The cyclic
      voltammetry results of these films confirmed that the hybrid films have redox
      activity by polyaniline. For these voltammograms, the maximum current was
      observed in the tin phosphate/polyaniline hybrid deposited for 15 min. The redox
      activity of these hybrids possibly depends on the mesoscopic texture of the film,
      especially on the amount of voids in a horizontal direction.

PMID- 18627187
TI  - Floating objects with finite resistance to bending.
AB  - We consider the equilibrium flotation of a thin, flexible cylinder at the
      interface between a liquid and a gas. In particular, we determine the maximum
      load that such a cylinder can support without sinking. We find that as the length
      of such a cylinder increases the maximum load at first increases. However, the
      maximum load reaches a plateau when the length of the cylinder is comparable to
      the elastocapillary length, which is determined by a balance between the bending
      of the cylinder and surface tension. We then consider the implications of our
      analysis for the walking on water of both arthropods and man-made robots. In
      particular, we show that the legs of water striders are typically slightly
      shorter than this 'optimal' length, suggesting that elastocapillary effects may
      act as a selection pressure.

PMID- 18627188
TI  - Topographical and functional characterization of the ssDNA probe layer generated
      through EDC-mediated covalent attachment to nanocrystalline diamond using
      fluorescence microscopy.
AB  - The covalent attachment method for DNA on nanocrystalline diamond (NCD),
      involving the introduction of COOH functionalities on the surface by
      photoattachment of 10-undecenoic acid (10-UDA), followed by the 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide (EDC)-mediated coupling to NH 2-labeled ssDNA,
      is evaluated in terms of stability, density, and functionality of the resulting
      biological interface. This is of crucial importance in DNA biosensor development.
      The covalent nature of DNA attachment will infer the necessary stability and
      favorable orientation to the ssDNA probe molecules. Using confocal fluorescence
      microscopy, the influence of buffer type for the removal of excess 10-UDA and
      ssDNA, the probe ssDNA length, the probe ssDNA concentration, and the presence of
      the COOH-linker on the density and functionality of the ssDNA probe layer were
      investigated. It was determined that the most homogeneously dense and functional
      DNA layer was obtained when 300 pmol of short ssDNA was applied to COOH-modified
      NCD samples, while H-terminated NCD was resistant for DNA attachment. Exploiting
      this surface functionality dependence of the DNA attachment efficiency, a shadow
      mask was applied during the photochemical introduction of the COOH
      functionalities, leaving certain regions on the NCD H-terminated. The subsequent
      DNA attachment resulted in a fluorescence pattern corresponding to the negative
      of the shadow mask. Finally, NCD surfaces covered with mixtures of the 10-UDA
      linker molecule and a similar molecule lacking the COOH functionality,
      functioning as a lateral spacer, were examined for their suitability in
      preventing nonspecific adsorption to the surface and in decreasing steric
      hindrance. However, purely COOH-modified NCD samples, patterned with H-terminated
      regions and treated with a controlled amount of probe DNA, proved the most
      efficient in fulfilling these tasks.

PMID- 18627189
TI  - Two-dimensional crystal structure of a quaterthiophene-alkanethiol self-assembled
      monolayer on gold.
AB  - We investigated the fine structure of a self-assembled monolayer of dodecanethiol
      functionalized by alpha-quaterthiophene on gold (alpha-4TC 12H 24SH). The
      molecular orientation, quantified using polarization modulation infrared
      reflection-absorption spectroscopy, was studied as a function of the adsorption
      time. The alpha-4T moieties arrange in the upright position on the surface as the
      adsorption time increases, while the alkyl chain organization remains poor. Here
      we quantify the orientation of the self-assembled monolayer and, more
      significantly, reveal through surface X-ray diffraction that after a long
      incubation period (12 h) the alpha-4T on the gold surface adopts a 2D crystal
      structure.

PMID- 18627190
TI  - Amino-substituted amphiphilic calixarenes: self-assembly and interactions with
      DNA.
AB  - The amphiphilic 5,11,17,23-tetramino-25,26,27,28-tetradodecyloxycalix[4]arene is
      shown to self-assemble as stable and well-defined Langmuir monolayers at the air
      water interface. The effect of the presence of DNA in the subphase reveals
      interactions taking place at the interface between the positively charged surface
      and the negatively charged DNA, causing an expansion of the monolayers and a
      phase transition from a liquid-condensed to a liquid-expanded phase; a slight
      decrease in the stability of the monolayers is also observed. The title compound
      is shown to self-assemble, with the absence of a cosurfactant, as stable
      colloidal suspensions. Photon correlation spectroscopy, zeta-potential
      measurements, and atomic force microscopy reveal that these colloidal suspensions
      present a monodisperse size distribution and are composed of positively charged
      solid lipid nanoparticles (SLNs), with an average hydrodynamic diameter of 190 nm
      and a surface potential of +13.2 mV. The interaction of these SLNs with double
      stranded DNA is demonstrated.

PMID- 18627191
TI  - Facile cell patterning on an albumin-coated surface.
AB  - Fabrication of micropatterned surfaces to organize and control cell adhesion and
      proliferation is an indispensable technique for cell-based technologies. Although
      several successful strategies for creating cellular micropatterns on substrates
      have been demonstrated, a complex multistep process and requirements for special
      and expensive equipment or materials limit their prevalence as a general
      experimental tool. To circumvent these problems, we describe here a novel facile
      fabrication method for a micropatterned surface for cell patterning by utilizing
      the UV-induced conversion of the cell adhesive property of albumin, which is the
      most abundant protein in blood plasma. An albumin-coated surface was prepared by
      cross-linking albumin with ethylene glycol diglycidyl ether and subsequent
      casting of the cross-linked albumin solution on the cell culture dish. While
      cells did not attach to the albumin surface prepared in this way, UV exposure
      renders the surface cell-adhesive. Thus, surface micropatterning was achieved
      simply by exposing the albumin-coated surface to UV light through a mask with the
      desired pattern. Mouse fibroblast L929 cells were inoculated on the patterned
      albumin substrates, and cells attached and spread in a highly selective manner
      according to the UV-irradiated pattern. Although detailed investigation of the
      molecular-level mechanism concerning the change in cell adhesiveness of the
      albumin-coated surface is required, the present results would give a novel facile
      method for the fabrication of cell micropatterned surfaces.

PMID- 18627192
TI  - Self-assembling of guanidine-type surfactant.
AB  - Self-assembling characteristics of dodecylguanidine hydrochloride (C 12G), a
      cationic surfactant with a guanidine group in its molecule, were investigated and
      compared with those of dodecyltrimethylammonium chloride (DTAC) and sodium
      dodecylsulfate (SDS). Introduction of a guanidine group into the surfactant
      molecule was found to increase its assembly formability more than that of the
      trimethylammonium group on the basis of the experimental results on the phase
      diagram, Kraft point, area occupied per molecule at the air-water interface, and
      micellar aggregation number of C 12G. Thermodynamic parameters for micelle
      formation suggested that an attractive force acts between guanidine groups of C
      12G molecules to facilitate their assembly formation. The presence of this force
      was evidenced by changes in the (1)H NMR and IR spectra before and after micelle
      formation of the guanidine-type (G-type) surfactant, indicating that the
      increased assembly formability is caused by an increase in hydrogen bonding
      between guanidine groups of the surfactant via water molecules.

PMID- 18627193
TI  - Electroactive self-assembled monolayers on gold via bipodal dithiazepane
      anchoring groups.
AB  - Novel dithiazepane-functionalized ferrocenyl-phenylethynyl oligomers 1 and 2 have
      been synthesized. Self-assembled monolayers (SAMs) of these ferrocene derivatives
      have been studied by X-ray photoelectron spectroscopy, ellipsometry, and cyclic
      voltammetry. It has been shown by XPS that monolayers of the dithiazepane
      anchored molecules on gold electrodes contain gold-thiolate species. Cyclic
      voltammetry of the SAMs were characteristic of stable electroactive monolayers
      even for single-component SAMs of 1 and 2, with the more ideal responses recorded
      for the two-component SAMs diluted with undecanethiol. The small variation in
      peak splittings at progressively higher scan rates in these SAMs makes
      dithiazepane-bridged redox species promising candidates for further studies on
      molecular wires with bipodal anchoring.

PMID- 18627194
TI  - Plasma-enhanced synthesis of thin fluoropolymer layers with low Raman and
      fluorescence backgrounds.
AB  - Radio-frequency (RF) plasma enhanced chemical vapor deposition (PECVD) provides a
      promising way to deposit extremely hydrophobic, highly adherent nanometer- to
      micrometer-thick films with thermal stability, a low coefficient of friction, a
      low dielectric constant, and a low value of surface energy. We describe the
      synthesis of these fluorinated thin films using hexafluoropropene as starting
      material and discuss their properties. These coatings, applied to stainless
      steel, provide ideal substrates for Raman spectroscopy, when extremely low
      backgrounds are required. Raman spectroscopy measurements of a low-concentration
      protein film are used to demonstrate sensitivity and level of detectability.

PMID- 18627195
TI  - Antibody targeting of camptothecin-loaded PLGA nanoparticles to tumor cells.
AB  - Antibody targeting of drug substances can improve the efficacy of the active
      molecule, improving distribution and concentration of the drug at the site of
      injury/disease. Encapsulation of drug substances into polymeric nanoparticles can
      also improve the therapeutic effects of such compounds by protecting the molecule
      until its action is required. In this current study, we have brought together
      these two rationales to develop a novel immuno-nanoparticle with improved
      therapeutic effect against colorectal tumor cells. This nanoparticle comprised a
      layer of peripheral antibodies (Ab) directed toward the Fas receptor (CD95/Apo-1)
      covalently attached to poly(lactide-co-glycolide) nanoparticles (NP) loaded with
      camptothecin. Variations in surface carboxyl density permitted up to 48.5 microg
      coupled Ab per mg of NP and analysis of nanoparticulate cores showed efficient
      camptothecin loading. Fluorescence visualization studies confirmed
      internalization of nanoconstructs into endocytic compartments of HCT116 cells, an
      effect not evident in NP without superficial Ab. Cytotoxicity studies were then
      carried out against HCT116 cells. After 72 h, camptothecin solution resulted in
      an IC 50 of 21.8 ng mL (-1). Ab-directed delivery of NP-encapsulated camptothecin
      was shown to be considerably more effective with an IC 50 of 0.37 ng mL (-1).
      Calculation of synergistic ratios for these nanoconstructs demonstrated synergy
      of pharmacological relevance. Indeed, the results in this paper suggest that the
      attachment of anti-Fas antibodies to camptothecin-loaded nanoparticles may result
      in a therapeutic strategy that could have potential in the treatment of tumors
      expressing death receptors.

PMID- 18627196
TI  - Effect of transferrin as a ligand of pH-sensitive fusogenic liposome-lipoplex
      hybrid complexes.
AB  - We previously developed potent nonviral vectors based on complexation of
      lipoplexes and pH-sensitive fusogenic liposomes, which achieve efficient
      transfection through membrane fusion with intracellular acidic compartments such
      as endosomes. Because transferrin receptor is known to be overexpressed in cancer
      cells, in this study, we investigated the effect of transferrin as a ligand for
      transfection of various cancer-derived cell lines mediated by the liposome
      lipoplex hybrid complexes. Results showed that these hybrid complexes with
      transferrin exhibited higher transfection efficiency toward these cells than
      complexes without transferrin, but the extent of the transferrin-induced
      enhancement was dependent on the cell line. Conjugation of transferrin increased
      their transfection activity for HeLa and KB cells, although it only slightly
      enhanced transfection for HT1080, HepG2, and K562. Transferrin receptors in
      HT1080, HepG2, and K562 cells were internalized slowly, whereas those in HeLa and
      KB cells were internalized quickly and actively. These results indicate that
      transfection mediated by the ligand-attached hybrid complex does not correlate
      with the amount of transferrin receptor in the cell surface but correlate with
      the activity of internalization of transferrin receptor into the cells.

PMID- 18627197
TI  - Acetal linked oligoethylenimines for use as pH-sensitive gene carriers.
AB  - Two types of acid-degradable nonviral gene carriers, OEI-MK and OEI-BAA, were
      synthesized by polymerizing oligoethylenimine of 800 Da (OEI800) with the pH
      sensitive acetone ketal cross-linker 2,2-bis(N-maleimidoethyloxy) propane (MK) or
      the 4-methoxybenzaldehyde bisacrylate acetal cross-linker 1,1-bis-(2-acryloyloxy
      ethoxy)-[4-methoxy-phenyl]methane) (BAA). Corresponding acid-insensitive
      counterparts (OEI-BM and LT-OEI-HD) were synthesized as well, representing
      control polymers. Kinetics of hydrolysis were measured and confirmed the pH
      dependent degradation profile of the acetal functions, with short half-lives of 3
      min at pH 5.0, and 5 h (OEI-MK) or 3.5 h (OEI-BAA) at physiological pH 7.4 and 37
      degrees C. DNA polyplexes of a luciferase expression plasmid were tested for gene
      transfer efficiency and biocompatibility in two cell lines (B16F10 and Neuro2A).
      Polyplexes with acid-labile polymers showed an improved toxicity profile compared
      to those made with acid-stable polymer analogues. At low cation/plasmid (c/p) w/w
      ratios the transfection efficiency of pH-sensitive polymers was slightly reduced,
      but it became similar or superior to the efficiency of acid-stable polymers at
      higher c/p ratios. An improved in vivo biocompatibility of the acid-degradable
      polymers over the stable control polymers was confirmed by liver histology after
      systemic administration of polymers in Balb/c mice.

PMID- 18627198
TI  - Site-specific labeling of annexin V with F-18 for apoptosis imaging.
AB  - Annexin V is useful in detecting apoptotic cells by binding to phosphatidylserine
      (PS) that is exposed on the outer surface of the cell membrane during apoptosis.
      In this study, we examined the labeling of annexin V-128, a mutated form of
      annexin V that has a single cysteine residue at the NH 2 terminus, with the thiol
      selective reagent (18)F-labeling agent N-[4-[(4
      [(18)F]fluorobenzylidene)aminooxy]butyl]maleimide ([(18)F]FBABM). We also
      examined the cell binding affinity of the (18)F-labeled annexin V-128 ([(18)F]FAN
      128). [(18)F]FBABM was synthesized in two-step, one-pot method modified from
      literature procedure. (Toyokuni et al., Bioconjugate Chem. 2003, 14, 1253-1259).
      The average yield of [(18)F]FBABM was 23 +/- 4% (n = 4, decay-corrected) and the
      specific activity was approximately 6000 Ci/mmol. The total synthesis time was
      approximately 92 min. The critical improvement of this study was identifying and
      then developing a purification method to remove an impurity N-[4-[(4
      dimethylaminobenzylidene)aminooxy]butyl]maleimide 4, whose presence dramatically
      decreased the yield of protein labeling. Conjugation of [(18)F]FBABM with the
      thiol-containing annexin V-128 gave [(18)F]FAN-128 in 37 +/- 9% yield (n = 4,
      decay corrected). Erythrocyte binding assay of [(18)F]FAN-128 showed that this
      modification of annexin V-128 did not compromise its membrane binding affinity.
      Thus, an in vivo investigation of [ (18)F]FAN-128 as an apoptosis imaging agent
      is warranted.

PMID- 18627199
TI  - Water-in-silicone oil emulsion stabilizing surfactants formed from native albumin
      and alpha,omega-triethoxysilylpropyl-polydimethylsiloxane.
AB  - Contact with hydrophobic silicones frequently leads to protein denaturation.
      However, it is demonstrated that albumin in water-in-silicone oil emulsions
      retains its native structure in the presence of a functional, triethoxysilyl
      terminated silicone polymer, TES-PDMS. Both HSA and TES-PDMS were essential for
      the formation of stable water-in-silicone oil emulsions: attempts to generate
      stable emulsions using independently either the protein or the functionalized
      silicone as a surfactant failed. Confocal microscopy indicated that the human
      serum albumin (HSA) preferentially adsorbed at the oil/water interface, even in
      the presence of another protein (glucose oxidase). A variety of experiments
      demonstrated that the hydrolysis of the Si-OEt groups on the functional silicone
      occurred only to a limited extent, consistent with the absence of a covalent
      linkage between the silicone and protein, or of cross-linked silicones at the
      interface. The fluorescence spectra of HSA extracted from the emulsions, front
      faced fluorescence experiments on the HSA/silicone emulsion itself, and
      HSA/salicylate binding studies all demonstrated that the stability of the
      water/oil interface decreased as the protein began to unfold: unfolding of the
      protein in the emulsion was slower than in aqueous solution. The experimental
      evidence indicated that the interaction between HSA and TES-PDMS is not
      associated with either homomolecular (HSA/HSA; TES-PDMS/TES-PDMS) interactions or
      with covalent linkage between two the polymers. Rather, the data is consistent
      with the direct binding of unhydrolyzed Si(OEt) 3 groups to native HSA. The
      nature of these interactions is discussed.

PMID- 18627201
TI  - Sesquiterpenes from the Hainan Sponge Dysidea septosa.
AB  - Five new sesquiterpenes, named lingshuiolides A (1) and B (2), lingshuiperoxide
      (6), isodysetherin (10), and spirolingshuiolide (12), along with several known
      related analogues (7- 9, 11, and 13- 15), were isolated from the Hainan marine
      sponge Dysidea septosa. The structures of new compounds 1, 2, 6, 10, and 12 were
      determined by detailed analysis of 1D and 2D NMR spectra and by comparison with
      related model compounds. The absolute configuration of lingshuiolide B (2) was
      established by using the modified Mosher's method. Spirolingshuiolide (12)
      represents the first example of a sesquiterpene with a rearranged drimane
      skeleton. Compounds 7- 9 and 15 exhibited significant inhibitory activity against
      human protein tyrosine phosphatase 1B (hPTP1B), an enzyme involved in the
      regulation of insulin signaling. In particular, 15 showed the most potent effect,
      with an IC 50 value of 1.9 microg/mL.

PMID- 18627202
TI  - High-throughput study of phenytoin solid dispersions: formulation using an
      automated solvent casting method, dissolution testing, and scaling-up.
AB  - A high-throughput experimentation method for studying the dissolution of
      phenytoin, a poorly water soluble drug, was developed and validated. Solid
      dispersions with 12 excipients (7 polymers and 5 surfactants) were prepared and
      tested. Each excipient was screened with three drug loadings: 10, 20, and 40%
      (w/w). Each solid dispersion was prepared in triplicate, for a total of 108
      samples. The drug dissolution was studied in simulated gastric fluid without
      pepsin plus 1% sodium laurylsulfate. This study led to the identification of
      three improved formulations, exhibiting an extent of dissolution higher than 90%
      after both 30 and 60 min. The HTE results could be reproduced at a larger scale
      using a conventional solvent evaporating method, proving the reliability of the
      HTE protocol.

PMID- 18627200
TI  - New design of helix bundle peptide-polymer conjugates.
AB  - We present a new design of peptide-polymer conjugates where a polymer chain is
      covalently linked to the side chain of a helix bundle-forming peptide. The effect
      of conjugated polymer chains on the peptide structure was examined using a de
      novo designed three-helix bundle and a photoactive four-helix bundle. Upon
      attachment of poly(ethylene glycol) to the exterior of the coiled-coil helix
      bundle, the peptide secondary structure was stabilized and the tertiary
      structure, that is, the coiled-coil helix bundle, was retained. When a heme
      binding peptide as an example is used, the new peptide-polymer conjugate
      architecture also preserves the built-in functionalities within the interior of
      the helix bundle. It is expected that the conjugated polymer chains act to
      mediate the interactions between the helix bundle and its external environment.
      Thus, this new peptide-polymer conjugate design strategy may open new avenues to
      macroscopically assemble the helix bundles and may enable them to function in
      nonbiological environments.

PMID- 18627203
TI  - FIB/TEM characterization of the composition and structure of core/shell Cu-Ni
      nanowires.
AB  - Characterization of composition and structure is crucial to understanding the
      properties and performance of nanomaterials. For nanowires and nanotubes,
      determining radial compositional and structural modulations is particularly
      challenging. Here we use a focused ion beam (FIB) lift-out technique to show that
      Cu-Ni core/shell nanowires fabricated by template synthesis are characterized by
      large, high purity (>99 atom %) copper grains surrounded by much smaller, high
      purity (>99 atom %) nickel grains.

PMID- 18627204
TI  - Uniform diffusion of acetonitrile inside carbon nanotubes favors supercapacitor
      performance.
AB  - An unusual behavior of liquid acetonitrile (AN) confined inside carbon nanotubes
      (CNTs) is predicted by molecular dynamics simulation. In contrast to water, which
      shows inhomogeneous variation of both translational and rotational diffusion with
      CNT diameter [ Nano Lett. 2003, 3, 589; 2004, 4, 619], the diffusion coefficient
      of AN changes uniformly and can be described by a simple analytic model. At the
      same time, the reorientation dynamics of AN vary irregularly in smaller CNTs
      because of specific packing structures. The uniform translational diffusion of
      the nonaqueous solvent is critical for stable performance of the new generation
      of supercapacitors [ Nat. Mater. 2006, 5, 987].

PMID- 18627205
TI  - Immunization in patients with HIV infection: are practical recommendations
      possible?
AB  - The purpose of this article is to review immunization recommendations for HIV
      infected individuals in resource-constrained countries, particularly in sub
      Saharan Africa. Recent evidence suggests that HIV-infected children are at risk
      for low immunization coverage in sub-Saharan Africa. Routine immunization is
      recommended for these children. In comparison with immunocompetent children,
      recommendations for live-attenuated vaccines differ in HIV-infected children.
      However, limited laboratory capacity to diagnose HIV infection amongst young
      children prevents the implementation of these HIV-specific guidelines in resource
      constrained countries. Re-immunization has been the focus of recent research in
      high- and middle-income countries. Findings show that children established on
      highly active antiretroviral therapy have suboptimal vaccine-specific immunity
      and may benefit from re-immunization. Before re-immunization guidelines can be
      formulated for resource-constrained countries, several questions should be
      addressed, including whether all HIV-infected children will benefit from routine
      re-immunization and what optimal number of vaccine doses should be administered.
      Pneumococcal and influenza infections are important causes of morbidity and
      mortality amongst HIV-infected individuals. There is compelling evidence showing
      that pneumococcal conjugate vaccines will protect HIV-infected and uninfected
      children against invasive infection. Pneumococcal conjugate vaccines should be
      prioritized for introduction in countries with high HIV prevalence. Although,
      annual influenza immunization is recommended for HIV-infected individuals, the
      effectiveness in Africa remains unclear. In conclusion, this brief overview has
      identified several limitations of current immunization policy and practice for
      HIV-infected individuals living in resource-constrained countries.

PMID- 18627206
TI  - Cell-based influenza vaccines: progress to date.
AB  - Human vaccines against influenza have been available for almost 60 years and,
      until recently, were prepared almost entirely from viruses grown in the allantoic
      cavity of 9- to 11-day-old embryonated chicken eggs. Manufacture involving eggs
      is not sufficiently flexible to allow vaccine supplies to be rapidly expanded,
      especially in the face of an impending pandemic. Other problems may arise from
      the infections of progenitor flocks that adversely affect egg supplies, and from
      the manufacturing process itself, where breakdowns in sterility can occur from
      the occasional contamination of large batches of viral allantoic fluid. In
      addition, egg-grown viruses exhibit differences in antigenicity from viruses
      isolated in mammalian cell lines from clinical specimens. These concerns and the
      probable need for greatly expanded manufacturing capability in the future have
      been brought into focus in recent years by the limited spread of H5N1 avian
      influenza infections to humans in several Asian countries. Alternative approaches
      involving the use of accredited anchorage-dependent and -independent preparations
      of the African Green monkey kidney (Vero), Madin-Darby canine kidney (MDCK) and
      other cell lines have been pursued by several manufacturers in recent years.
      Yields comparable with those obtained in embryonated eggs have been achieved.
      These improvements have occurred in parallel with newer technologies that allow
      the growth of cells in newer synthetic media that do not contain animal serum, in
      order to allay the concerns of regulators about the potential for spread of
      transmissible spongiform encephalopathies.

PMID- 18627207
TI  - Depressive symptoms in epilepsy: prevalence, impact, aetiology, biological
      correlates and effect of treatment with antiepileptic drugs.
AB  - Occurring in up to 80% of patients with epilepsy, depression in epilepsy may
      manifest as (i) major depressive disorder, meeting Diagnostic and Statistical
      Manual, 4th edition (DSM-IV) diagnostic criteria; (ii) atypical depression or
      dysthymia; or (iii) a dysthymic-like disorder with intermittent symptoms that can
      be milder than those of major depression. Depressive symptoms impair patients'
      health-related quality of life and may affect the clinical course of epilepsy.
      Depressive symptoms in epilepsy have been attributed to several causes, including
      endocrine and/or metabolic effects of seizures; the psychological response to
      epilepsy and its associated mental, physical and social challenges; common
      pathogenic mechanisms between depression and epilepsy; and the adverse effects of
      certain antiepileptic drugs (AEDs), particularly GABAergic agents, such as
      vigabatrin, tiagabine, topiramate and phenobarbital. Whereas some AEDs impair
      mood, others appear to improve aspects of mood or are mood neutral. Demonstrable
      antidepressant efficacy of AEDs used to manage seizures could have a significant
      impact on the care of patients with epilepsy. The AED lamotrigine has been
      demonstrated to be effective in the treatment of depressive symptoms in patients
      with epilepsy. In randomized, double-blind, clinical trials in patients with
      epilepsy, depressive symptoms improved more with lamotrigine monotherapy than
      valproate monotherapy and more with lamotrigine adjunctive therapy than placebo.
      Results of open-label studies of lamotrigine monotherapy and adjunctive therapy
      are consistent with the results of double-blind clinical trials. Lamotrigine
      associated improvement in depressive symptoms is independent of its
      anticonvulsant efficacy. In prospective assessments, gabapentin, levetiracetam
      and oxcarbazepine each exhibited potentially beneficial effects on depressive
      symptoms in patients with epilepsy. However, evidence for the efficacy of
      gabapentin, levetiracetam and oxcarbazepine in the treatment of depressive
      symptoms in epilepsy is inconclusive at present because the effects of each agent
      have only been reported in single studies of an open-label design and with small
      sample sizes.

PMID- 18627209
TI  - Lutropin alfa.
AB  - Lutropin alfa is the first and only recombinant human form of luteinizing hormone
      (LH) developed for use in the stimulation of follicular development. Dose-finding
      studies revealed a significant dose-dependent increase in the rate of optimal
      follicular development among women with hypogonadotropic hypogonadism and
      profound LH deficiency (<1.2 IU/L) who received subcutaneous lutropin alfa 0-225
      IU/day plus follitropin alfa. Similarly, in a double-blind, randomized study, the
      rate of optimal follicular development was significantly higher in women with
      hypogonadotropic hypogonadism and profound LH deficiency receiving subcutaneous
      lutropin alfa 75 IU/day plus follitropin alfa than in those receiving placebo
      plus follitropin alfa. Lutropin alfa with follitropin alfa may also be of benefit
      in certain subgroups of normogonadotropic women (e.g. those with an inadequate
      response to prior follitropin alfa monotherapy, those aged >or=35 years, and
      those with profound LH downregulation or who required excessive exogenous
      follitropin alfa). However, one study in older women (>or=35 years) did not show
      any advantage of lutropin alfa supplementation. Once-daily subcutaneous lutropin
      alfa was generally well tolerated in hypogonadotropic hypogonadal women, with the
      majority of adverse events being of mild to moderate severity.

PMID- 18627210
TI  - Lutropin alfa: a viewpoint by Giuseppe De Placido, Roberto Clarizia and Carlo
      Alviggi.

PMID- 18627208
TI  - Cigarette smoking and diffuse lung disease.
AB  - Cigarette smoke, a toxic collection of more than 4000 chemicals generated from
      combustion of tobacco plant leaves, is known to cause several respiratory
      ailments, including chronic bronchitis, emphysema and lung cancer, and is
      associated with an increase in respiratory infections. In addition, cigarette
      smoking is considered a principal aetiological factor responsible for the
      development of certain diffuse interstitial and bronchiolar lung diseases, namely
      respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative
      interstitial pneumonia (DIP) and adult pulmonary Langerhans' cell histiocytosis
      (PLCH). Although not exclusively seen in cigarette smokers, substantial clinical
      and epidemiological data support a central role for smoking as the primary
      causative agent of most RB-ILD, DIP and PLCH. Additional evidence in support of
      cigarette smoke as a primary aetiological agent in RB-ILD, DIP and PLCH is the
      observation that smoking cessation may lead to disease improvement, while
      recurrence of these disorders has been observed to occur in the transplanted lung
      upon re-exposure to tobacco smoke. Furthermore, histopathological changes of
      respiratory bronchiolitis, DIP and PLCH (with or without co-existent emphysema)
      may be found on lung biopsy in the same individual, implicating smoking as a
      common inciting agent of these diverse lesions. Recent studies also suggest a
      role for cigarette smoking as a potential co-factor in the development of acute
      eosinophilic pneumonia, usual interstitial pneumonia and rheumatoid arthritis
      associated interstitial lung disease. In the current review, we propose a novel
      classification that takes into account the complex relationship between cigarette
      smoking and diffuse lung diseases. Investigation on the role of smoking as a
      potential causative factor or modifier of these diverse diffuse lung diseases is
      important, as smoking cessation utilizing state-of-the-art tobacco cessation
      efforts should be a central part of therapy, while pharmacotherapy with
      corticosteroids or other immune modifying agents should be reserved for selected
      patients.

PMID- 18627211
TI  - Lutropin alfa: a viewpoint by Peter Humaidan.

PMID- 18627214
TI  - Impacts of climate change and establishing a vegetation cover on water erosion of
      contaminated spoils for two contrasting United Kingdom regional climates: a case
      study approach.
AB  - This study examines how pollutant linkage of contaminants will be influenced by
      predicted changes in precipitation and subsequent rainfall erosion of soils and
      spoils in the United Kingdom during the 21st century. Two contrasting regional
      climates were used in conjunction with 2 extreme emissions scenarios (low and
      high greenhouse gas emissions) to run the Revised Universal Soil Loss Equation 2
      (RUSLE2) model for a case study that represents a high risk of pollutant linkage
      through water erosion. Results for the 2 scenarios and the 2 regions showed a
      significant and gradual increase in erosion rates with time as a consequence of
      climate change, by up to 32% for the southwest and 6.6% for the southeast regions
      by the 2080s. Revegetation of the site showed a dramatic reduction in predicted
      future amounts of sediment production and subsequent contaminant movement, well
      below existing levels. Limitations and future improvements of the methodology are
      discussed.

PMID- 18627215
TI  - Patients are more likely to use complementary medicine if it is locally
      available.

PMID- 18627212
TI  - Irbesartan: a review of its use in hypertension and diabetic nephropathy.
AB  - Irbesartan (Aprovel, Avapro, Irbetan, Karvea), an angiotensin II receptor type 1
      antagonist, is approved in many countries worldwide for the treatment of
      hypertension. It is also approved in some regions for the treatment of
      nephropathy in patients with hypertension and type 2 diabetes mellitus. In adults
      with essential hypertension, irbesartan is effective at reducing blood pressure
      (BP) over a 24-hour period with once-daily administration. Irbesartan also slows
      the progression of renal disease in hypertensive patients with type 2 diabetes,
      with this effect partly independent of its BP-lowering effect. In addition,
      irbesartan was generally well tolerated in clinical trials. Thus, irbesartan is a
      useful treatment option for patients with hypertension, including those with type
      2 diabetes and nephropathy.

PMID- 18627213
TI  - Esomeprazole: a review of its use in the management of gastric acid-related
      diseases in adults.
AB  - Esomeprazole (Nexium); S-omeprazole) is a single optical isomer proton-pump
      inhibitor (PPI) approved for the management of reflux oesophagitis, the
      symptomatic treatment of gastro-oesophageal reflux disease (GORD), the prevention
      and healing of NSAID-associated gastric ulcer disease (and the prevention of
      NSAID-associated duodenal ulcers in the UK), the treatment of Helicobacter pylori
      infection and associated duodenal ulcer disease (and prevention of relapse of H.
      pylori-associated peptic ulcers in the UK), and the treatment of Zollinger
      Ellison syndrome (and other hypersecretory syndromes in the US).Once-daily oral
      esomeprazole 40 mg demonstrates greater antisecretory activity than other PPIs.
      Overall, in well designed clinical studies of 4 weeks' to 6 months' duration in
      patients with GORD, esomeprazole had similar or better efficacy than other
      agents. In patients requiring ongoing treatment with NSAIDs, co-therapy with once
      daily esomeprazole 20 or 40 mg achieved relief of gastrointestinal symptoms or
      prevented ulcer occurrence, more effectively than placebo. Esomeprazole was also
      better than ranitidine 150 mg twice daily in healing NSAID-associated gastric
      ulcers. In addition, the drug has demonstrated efficacy as part of a triple
      therapy regimen for the eradication of H. pylori infection, the healing of H.
      pylori associated duodenal ulcers and the prevention of relapse of gastric
      ulcers. Esomeprazole also effectively treated patients with Zollinger-Ellison
      syndrome. Esomeprazole is generally well tolerated with an adverse-event profile
      similar to that of other PPIs. Thus, the efficacy and tolerability of
      esomeprazole for the management of GORD and H. pylori eradication remains
      undisputed, and the data support its use for the first-line treatment of NSAID
      associated gastric ulcer disease and Zollinger-Ellison syndrome.

PMID- 18627216
TI  - Myocardial infarction and heart failure hospitalization rates in Maine, USA -
      variability along the urban-rural continuum.
AB  - INTRODUCTION: Cardiovascular disease, including myocardial infarction (MI) and
      heart failure (HF), remains the leading cause of death in wealthy countries and
      is of increasing concern in low- and middle-income countries as risk factors such
      as smoking and obesity become more common around the globe. Within each country
      the health burden of MI and HF generally falls more heavily on those who live in
      rural areas and on those who live in communities with lower average socioeconomic
      status (SES). Hospitalization rates are an important measure of community health
      because high rates may indicate a high burden of poor health, while
      inappropriately low rates (low hospitalization rates absent evidence of average
      good health) may indicate underutilization of health services. The objective of
      this study was to determine the predictors of MI and HF hospitalization rates at
      town level in the State of Maine, USA. Maine has large variations in wealth and
      along the urban-rural continuum at town level. Because our results shed light on
      variations in health and health-seeking behavior for different Maine populations
      (such as those living closer vs further from hospitals) they may be of interest
      to providers of healthcare to people who live in areas remote from healthcare,
      and to people who face other barriers to good cardiovascular health. METHODS: To
      determine predictors of HF and MI hospitalization in Maine, we constructed a
      geographic information system (GIS) for Maine's towns using publicly available
      electronic map layers, year 2000 census data, and electronic hospitalization
      records for all Maine hospitals. This GIS generated age-corrected MI and HF
      hospitalization rates for 1998-2002 as dependent variables and the following
      independent variables: poverty rate, unemployment rate, median income,
      educational attainment, rurality, physician density, and distance to the closest
      hospital. Univariable and multiple linear regression analysis were then performed
      to determine the significant predictors of MI and HF hospitalization rates.
      RESULTS: During the 5-year study period there were 24 452 hospitalizations of
      Maine residents to Maine hospitals for MI and 20 330 for HF. In multiple linear
      regression analysis, greater unemployment, a larger fraction of the population
      living in poverty, and proximity to a hospital predicted higher MI
      hospitalization rate (p = 0.000, r-sq = 19.1%) while greater unemployment and
      proximity to a hospital predicted higher HF hospitalization rate (p = 0.000, r-sq
      = 8.4%). CONCLUSIONS: Our finding that higher MI and HF hospitalization rates
      were predicted for towns that had lower SES is in agreement with many previous
      studies and shows the importance of these variables to health, even in a setting
      such as Maine with large variability in rurality. The negative relationship
      between the distance to a hospital and hospitalization rates likely does not
      represent better health in those living remotely from healthcare. Rather, it may
      indicate that people who live in communities distant from hospitals are less
      likely to seek hospitalization. This suggests that patient behavior as well as
      socioeconomic status may impact heart-related hospitalization in Maine. It
      highlights the importance of patient and provider education to ensure that people
      who live remotely from health care are hospitalized appropriately.

PMID- 18627217
TI  - Desired attributes of new graduate nurses as identified by the rural community.
AB  - INTRODUCTION: Preparing nurse graduates for practice is challenging because of
      the diversity of skills expected of them. Increasingly consumers are more
      informed and expect quality care. OBJECTIVE: To identify the attributes a rural
      community expect in new graduate nurses in order for them to provide quality
      care. METHODS: A questionnaire was designed to assess the importance attached to
      a set of attributes of graduate nurses expected by a rural community. The
      community included a range of professionals working with government and
      hospitals, community volunteers and retired people. After pilot testing, the
      questionnaire was distributed using a cluster sampling technique. A total of 656
      completed questionnaires were returned, giving a response rate of 69%. The
      respondents were asked to rate the importance of each item for the community on a
      five-point Likert scale (5 = extremely important, 4 = very important, 3 =
      moderately important, 2 = possibly importantly, and 1 = not important at all).
      Exploratory factor analysis was performed on the 38 items using SPSS (SPSS inc;
      Chicago, IL, USA). Principal Components Analysis was applied to identify the
      number of factors followed by Oblimin rotation. RESULTS: The sample of 656
      respondents consisted of 68% females and 30% males (2% did not identify their
      gender). The majority of the respondents (75.6%) were born in Australia, while
      3.2% were born in the UK Kingdom. Principal Components Analysis identified five
      factors with eigenvalues above one, explaining 47.4% of the total variance. Items
      that loaded greater than + or - 0.3, (approximately 10% of the common factor
      variance) was associated with the factor in question. Component 1 was labelled
      Sympathetic/ Patients' welfare with the item 'Nurses should be sensitive to the
      emotional needs of patients' showing the highest loading. Component 2 was called
      Contextual knowledge/ Interpersonal skills. It contained items indicating that
      nurses should have good personal skills and possess a broad contextual knowledge
      of issues associated with the practice of their profession, including financial,
      legal, economic, resources and social matters. Component 3 was titled
      Professionalism and contained items relating to professional behaviour, including
      the application of theory to daily nursing practice, ability to work in a team,
      and to accept the guidance given by their colleagues. The fourth component was
      identified as Personal attributes, with items relating to personal appearance
      (neat and tidy), personality (cheerful, patient) and skills (good organizational
      and time management skills. The fifth component was Accountability, and contained
      items such as, 'Nurses should be able to recognise their own limitations'.
      CONCLUSIONS: The attributes perceived by a rural community in new nurse graduates
      related to sympathetic/ patients' welfare, contextual knowledge/interpersonal
      skills, professionalism, personal attributes, and accountability. Preparing
      nurses to work in rural settings requires consideration of many aspects
      including: educational programs; employer support; planned and coordinated rural
      orientation strategy; and rural support issues, among others. The attributes
      identified in this study could be used to better guide the training and
      preparation of nurses for employment in rural settings.

PMID- 18627218
TI  - Enhancement of HIV infection by cellulose sulfate.
AB  - Cellulose sulfate, a polyanionic compound derived from cotton, has been proposed
      as a topical microbicide to reduce the sexual transmission of HIV. However, a
      phase III clinical trial of a vaginal gel formulation of cellulose sulfate
      (Ushercell) had to be prematurely closed after early data indicated microbicide
      users had a higher rate of HIV infection than women using a placebo. The
      unexpected results of the cellulose sulfate trail prompted us to reexamine and
      attempt to replicate the available preclinical data for this compound and other
      polyanions. We show here that cellulose sulfate has a biphasic effect on HIV
      infection in vitro: at high concentrations it inhibits infection but at low
      concentrations it significantly and reproducibly increases HIV infection. This
      stimulatory effect is evident for the R5-tropic strains of virus responsible for
      sexual transmission, reflects the rate of infection rather than viral growth, and
      occurs at clinically relevant concentrations of the compound. An examination of
      published studies shows that the biphasic effect of cellulose sulfate was evident
      in previous research by independent laboratories and is also found for other
      polyanions such as dextrin sulfate and PRO2000. These data help in understanding
      the failure of the Ushercell clinical trial and indicate that cellulose sulfate
      is not safe for mucosal application in humans.

PMID- 18627221
TI  - A meeting of minds on the welfare of beef cattle.

PMID- 18627219
TI  - RNA interference-mediated in vivo silencing of fas ligand as a strategy for the
      enhancement of DNA vaccine potency.
AB  - Intradermal administration of DNA vaccines encoding luciferase represents a
      convenient method to assess gene expression in vivo. Gene silencing by
      intradermal gene gun administration of DNA encoding short hairpin RNA (shRNA) may
      represent an effective technique for the specific knockdown of gene expression in
      vivo. In the current study, we characterized luciferase gene expression over time
      in vivo by noninvasive bioluminescence imaging. Furthermore, we characterized in
      vivo luciferase gene silencing with DNA encoding shRNA targeting luciferase. We
      also characterized human papillomavirus type 16 (HPV-16) E7-specific CD8(+) T
      cell immune responses in mice immunized with E7 DNA and DNA encoding shRNA
      targeting Fas ligand (FasL), a key proapoptotic signaling protein. Our results
      indicated that coadministration of DNA encoding shRNA targeting luciferase
      significantly reduced luciferase expression in mice intradermally administered
      luciferase DNA. Furthermore, we observed that mice vaccinated with E7-expressing
      DNA coadministered with DNA encoding shRNA targeting FasL generated significantly
      enhanced E7-specific CD8(+) cytotoxic T cell responses as well as potent
      therapeutic antitumor effects against E7-expressing tumors. Thus, intradermal
      administration of DNA encoding shRNA represents a plausible approach to silence
      genes in vivo and a potentially useful tool to enhance DNA vaccine potency.

PMID- 18627222
TI  - Thoughts on grading systems for soft tissue sarcomas.

PMID- 18627223
TI  - What is your diagnosis? Vesica fellea duplex.

PMID- 18627224
TI  - ECG of the month. Exaggerated sinus arrhythmia and wandering pacemaker.

PMID- 18627225
TI  - Theriogenology question of the month. Follicular cysts.

PMID- 18627226
TI  - Veterinary student and veterinarian attitudes toward veterinary public health and
      epidemiology.
AB  - OBJECTIVE: To identify predictors of veterinary students and veterinarians having
      an interest in veterinary public health and epidemiology (PH&E). DESIGN: Cross
      sectional study. SAMPLE POPULATION: Veterinary students enrolled in the College
      of Veterinary Medicine and Biomedical Sciences at Texas A&M University and
      veterinarians with membership in a Texas veterinary professional organization.
      PROCEDURES: 2 questionnaires were designed and administered to investigate
      hypothesized predictors of PH&E interests among veterinary students and
      veterinarians. Descriptive statistics were calculated for all variables from both
      questionnaires. Prevalence ratios, 95% confidence intervals, and chi(2) tests
      were used to evaluate bivariate associations between variables and an interest in
      PH&E. Multivariable logistic regression was used to adjust for the effects of
      multiple variables on the outcome. RESULTS: 70% (215/305) of students believed
      that a course in PH&E was necessary, and 46% (140/304) believed that more courses
      in PH&E would improve the veterinary curriculum. Ninety-nine percent (299/303) of
      veterinarians believed that a course in PH&E was necessary in the curriculum.
      Ninety-two percent (272/297) of veterinarians agreed that knowledge related to
      PH&E was important to perform the functions of their job. History of raising
      animals and membership in 4-H or Future Farmers of America were significant
      predictors of veterinary students having an interest in PH&E. Being male and
      growing up in a rural environment were not significant predictors. CONCLUSIONS
      AND CLINICAL RELEVANCE: Most veterinary students and veterinarians agreed that
      knowledge of PH&E is important. Variables identified as associated with an
      interest in PH&E may be useful for designing mitigation strategies to increase
      the number of veterinarians entering public health careers.

PMID- 18627227
TI  - Comparison of published recommendations regarding biosecurity practices for
      various production animal species and classes.
AB  - OBJECTIVE: To compare published recommendations regarding biosecurity practices
      for various production animal species and classes. DESIGN: Literature review.
      POPULATION: Educational materials available on the World Wide Web that provided
      biosecurity recommendations for dairy cattle, beef cattle, small ruminant, swine,
      and poultry producers. PROCEDURES: Web sites for national producer organizations,
      university cooperative extension services, and state departments of agriculture
      were searched to identify educational materials with biosecurity recommendations.
      RESULTS: A single national organization was selected as representing each animal
      agriculture commodity group. A total of 53 university Web sites were visited, and
      65 publications prepared by university cooperative extension services were
      identified and evaluated. Web sites for all 50 state departments of agriculture
      were searched, and 29 were found to have at least 1 publication related to
      biosecurity practices, for a total of 46 publications. Evaluation of the
      biosecurity recommendations revealed wide variations by source and within and
      among commodity groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that educational materials for producers contained wide variations in recommended
      biosecurity practices. It is possible that some producers choose not to implement
      biosecurity recommendations because of confusion as to the specific
      recommendations they should follow.

PMID- 18627228
TI  - Executive summary of the AVMA One Health Initiative Task Force report.

PMID- 18627229
TI  - Comparison of anesthetic induction in cats by use of isoflurane in an anesthetic
      chamber with a conventional vapor or liquid injection technique.
AB  - OBJECTIVE: To compare 2 techniques for induction of cats by use of isoflurane in
      an anesthetic chamber. DESIGN: Prospective, randomized study. ANIMALS: 51 healthy
      cats. PROCEDURES: Cats were randomly allocated to 2 induction techniques. Cats
      were premedicated with acepromazine (0.1 mg/kg [0.045 mg/lb], SC) and
      buprenorphine (0.01 mg/kg [0.0045 mg/lb], SC) 30 minutes before induction. Cats
      were then placed into an induction chamber, and anesthetic induction was
      initiated. One technique involved a conventional flow-through system that used an
      oxygen flowmeter and an isoflurane vaporizer to flow vapors into the induction
      chamber. Alternatively, liquid isoflurane was injected into a vaporization tray
      that was mounted to the interior surface of the chamber lid. Inductions were
      videotaped for analysis. Five variables (head bobbing, head swinging side to
      side, paddling, rotating 180 degrees to 360 degrees, and rolling over or
      flipping) were scored to assess induction quality. Time variables recorded during
      induction corresponded to the interval until onset of excitatory motion, duration
      of excitatory motion, interval until recumbency, and interval until complete
      induction. RESULTS: Compared with cats anesthetized by use of a conventional
      vapor chamber technique, cats anesthetized by use of the liquid injection
      technique had a significantly shorter interval until recumbency and interval
      until complete induction and lower scores for quality of induction, indicating a
      smoother induction. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthetic induction in
      cats by use of a liquid injection technique was more rapid and provided a better
      quality of induction, compared with results for cats induced by use of a
      conventional vapor technique.

PMID- 18627231
TI  - Severe reaction to intravenous administration of an ionic iodinated contrast
      agent in two anesthetized dogs.
AB  - CASE DESCRIPTION: Acute severe systemic reactions developed during i.v.
      administration of an ionic iodinated contrast agent (iothalamate meglumine) in 2
      dogs undergoing contrast-enhanced computed tomography. CLINICAL FINDINGS: Both
      dogs developed marked changes in heart rate and systolic arterial blood pressure
      during or immediately after i.v. administration of the contrast agent. The first
      dog became profoundly hypertensive and bradycardic with poor oxygenation,
      apparent bronchospasm, and prolonged diarrhea. The second dog became hypotensive
      and tachycardic with erythema on the ventral aspect of the abdomen and pelvic
      limbs, periocular edema, and diarrhea. TREATMENT AND OUTCOME: Both dogs were
      treated for shock by means of i.v. fluid administration, and anesthesia was
      discontinued. The first dog was placed on a ventilator to improve oxygenation but
      was hypertensive and unresponsive for 6.5 hours following contrast agent
      administration. Bloody diarrhea persisted once consciousness was regained. The
      dog was discharged 3 days after contrast agent administration, and diarrhea
      resolved 15 days later. The second dog responded to phenylephrine administration,
      but urine output appeared low immediately following recovery from anesthesia.
      Urine output was normal the following day, and the dog was released 36 hours
      after contrast administration with no residual adverse effects. CLINICAL
      RELEVANCE: Findings highlighted the potential risk for severe reactions
      associated with i.v. administration of ionic iodinated contrast agents in dogs.
      Both hypertensive and hypotensive responses were seen. Supportive care for
      systemic manifestations was effective in these 2 dogs, and extended
      hospitalization was not necessary.

PMID- 18627230
TI  - Analgesic efficacy of butorphanol and morphine in bearded dragons and corn
      snakes.
AB  - OBJECTIVE: To test the hypothesis that administration of butorphanol or morphine
      induces antinociception in bearded dragons and corn snakes. DESIGN: Prospective
      crossover study. ANIMALS: 12 juvenile and adult bearded dragons and 13 corn
      snakes. PROCEDURES: Infrared heat stimuli were applied to the plantar surface of
      bearded dragon hind limbs or the ventral surface of corn snake tails. Thermal
      withdrawal latencies (TWDLs) were measured before (baseline) and after SC
      administration of physiologic saline (0.9% NaCl) solution (equivalent volume to
      opioid volumes), butorphanol tartrate (2 or 20 mg/kg [0.91 or 9.1 mg/lb]), or
      morphine sulfate (1, 5, 10, 20, or 40 mg/kg [0.45, 2.27, 4.5, 9.1, or 18.2
      mg/lb]). RESULTS: For bearded dragons, butorphanol (2 or 20 mg/kg) did not alter
      hind limb TWDLs at 2 to 24 hours after administration. However, at 8 hours after
      administration, morphine (10 and 20 mg/kg) significantly increased hind limb
      TWDLs from baseline values (mean +/- SEM maximum increase, 2.7+/-0.4 seconds and
      2.8+/-0.9 seconds, respectively). For corn snakes, butorphanol (20 mg/kg)
      significantly increased tail TWDLs at 8 hours after administration (maximum
      increase from baseline value, 3.0+/-0.8 seconds); the low dose had no effect.
      Morphine injections did not increase tail TWDLs at 2 to 24 hours after
      administration. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with doses used in
      most mammalian species, high doses of morphine (but not butorphanol) induced
      analgesia in bearded dragons, whereas high doses of butorphanol (but not
      morphine) induced analgesia in corn snakes.

PMID- 18627233
TI  - Retinopathy associated with ivermectin toxicosis in two dogs.
AB  - CASE DESCRIPTION: 2 dogs (dogs 1 and 2) were examined for sudden onset of
      blindness. Both dogs had mild obtundation and mydriasis in both eyes. It was
      thought that dog 1 may have ingested ivermectin; dog 2 had been treated with
      ivermectin for demodectic mange. CLINICAL FINDINGS: On initial examination, both
      dogs had mydriasis and decreased pupillary light reflexes in both eyes. Dog 1 had
      an absent menace response bilaterally. Fundic examination of both eyes in both
      dogs revealed regions of multifocal retinal edema and folds with low-lying
      retinal separation. The electroretinogram was extinguished in dog 1 and
      attenuated in dog 2. Ivermectin was detected in serum samples from both dogs.
      TREATMENT AND OUTCOME: Both dogs made a complete clinical recovery following
      cessation of exposure to ivermectin; electroretinographic findings improved, and
      retinal edema resolved with some residual chorioretinal scarring. CLINICAL
      RELEVANCE: To our knowledge, this is the first report of resolution of retinal
      edema and electroretinographic changes associated with ivermectin toxicosis in
      dogs. In dogs that develop blindness suddenly, fundic examination,
      electroretinography, and assessment of serum ivermectin concentration are
      diagnostically useful, even if exposure to ivermectin is unknown.

PMID- 18627235
TI  - Exophthalmus secondary to a sinonasal cyst in a horse.
AB  - CASE DESCRIPTION: A 13-year-old female Miniature Horse was evaluated for
      progressive unilateral exophthalmia of the left globe of 3 weeks' duration.
      CLINICAL FINDINGS: Results of a physical examination were unremarkable.
      Ophthalmic examination identified exophthalmus of the left globe with complete
      resistance to retropulsion and mild blepharoconjunctivitis. Computed tomography
      revealed a large, space-occupying mass within the left caudal maxillary and left
      conchofrontal sinuses. The mass extended into the left retrobulbar space and
      contacted the cribriform plate. Trephination yielded copious amounts of turbid
      yellow fluid. The diagnosis was a sinonasal cyst. TREATMENT AND OUTCOME: Subtotal
      surgical excision of the cyst via a frontonasal osteoplastic flap was curative,
      with complete resolution of the exophthalmus. Histologic examination confirmed
      diagnosis of a sinonasal cyst. There was no evidence of cyst recurrence by 4
      months after surgery. CLINICAL RELEVANCE: Sinonasal cyst should be a differential
      diagnosis for retrobulbar disease in horses. Exophthalmia may be the only
      clinical finding in horses with a sinonasal cyst.

PMID- 18627236
TI  - Effect of intranasal oxygen administration on blood gas variables and outcome in
      neonatal calves with respiratory distress syndrome: 20 cases (2004-2006).
AB  - OBJECTIVE: To determine the effect of intranasal oxygen administration on blood
      gas variables and outcome in neonatal calves with respiratory distress syndrome
      (RDS). DESIGN: Retrospective case series. ANIMALS: 20 neonatal calves with RDS.
      PROCEDURES: Arterial partial pressure of oxygen (PaO(2)), arterial partial
      pressure of carbon dioxide, and arterial oxygen saturation (SaO(2)) before and
      after intranasal administration of oxygen were analyzed. RESULTS: There were
      significant increases in PaO(2) and SaO(2) in the first 24 hours after oxygen
      administration was begun, with mean +/- SD PaO(2) increasing from 38.4+/-8.8 mm
      Hg to 58.7+/-17.8 mm Hg during the first 3 hours of treatment. Calves with
      PaO(2)>55 mm Hg within the first 12 hours after oxygen administration was begun
      had a significantly higher survival rate (9/10) than did calves that did not
      reach this threshold (4/10). CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that intranasal oxygen administration was a simple method of improving
      blood gas variables in neonatal calves with RDS and that PaO(2) could be used to
      predict outcome.

PMID- 18627238
TI  - Cryptosporidiosis in 20 alpaca crias.
AB  - CASE DESCRIPTION: 20 alpaca crias (13 females and 7 males) were examined for
      diarrhea (n=20), weight loss (15), and poor appetite (5). Fourteen crias were
      between 8 and 18 days of age at time of admission. CLINICAL FINDINGS:
      Cryptosporidiosis was diagnosed in all crias. Common biochemical abnormalities
      included acidemia, hyperlactemia, azotemia, and hyperglycemia and increases in
      aspartate transaminase and gamma-glutamyltransferase activities. Serum sodium and
      chloride concentrations were high or low. Other potential gastrointestinal tract
      pathogens were identified in only 7 crias. TREATMENT AND OUTCOME: Supportive care
      was instituted, including i.v. administration of fluids with partial parenteral
      administration of nutrients (n=19 crias), antimicrobials (19), supplemental
      orally administered nutrients (11), administration of plasma (10), and insulin
      treatment (9). Other palliative treatments used by attending clinicians were
      sucralfate, flunixin meglumine, vitamin A/D/E/B complex, antiparasitic agents,
      antidiarrheal agents, and azithromycin. Three crias with inadequate urine
      production and severe azotemia were treated with furosemide administered i.v. as
      a bolus or as a constant-rate infusion. Treatment resulted in a successful
      outcome in 16 of 20 crias. Weight loss and refractory azotemia were common in
      nonsurvivors but not in surviving crias. CLINICAL RELEVANCE: Findings suggested
      that Cryptosporidium spp may be a diarrheal pathogen of unweaned alpaca crias
      that may be more widespread than has been recognized and can become endemic on
      some farms. Metabolic derangements were unpredictable and should be determined by
      biochemical analysis before fluid and electrolyte replacement is initiated.
      Cryptosporidiosis has zoonotic potential, and the infection can be self-limiting
      in alpacas receiving supportive treatment.

PMID- 18627240
TI  - Evaluation and comparison of the health status of Atlantic bottlenose dolphins
      from the Indian River Lagoon, Florida, and Charleston, South Carolina.
AB  - OBJECTIVE: To conduct health assessments and compare outcomes in 2 populations of
      Atlantic bottlenose dolphins. Design-Repeated cross-sectional study. ANIMALS: 171
      Atlantic bottlenose dolphins. PROCEDURES: During June and August of 2003 through
      2005, 89 dolphins from the Indian River Lagoon (IRL), Florida, and 82 dolphins
      from estuarine waters near Charleston, SC, were evaluated. A panel of 5 marine
      mammal veterinarians classified dolphins as clinically normal, possibly diseased,
      or definitely diseased on the basis of results of physical and ultrasonographic
      examinations, hematologic and serum biochemical analyses, and cytologic and
      microbiologic evaluations of gastric contents and swab specimens. RESULTS:
      Prevalence of dolphins classified as definitely diseased did not differ
      significantly between the IRL (32%) and Charleston (20%) sites. Proportions of
      dolphins classified as possibly diseased also did not differ. Lobomycosis was
      diagnosed in 9 dolphins from the IRL but in none of the dolphins from Charleston.
      Proportions of dolphins with orogenital papillomas did not differ significantly
      between the IRL (12%) and Charleston (7%) sites. From 2003 through 2005, the
      proportion classified as definitely diseased tripled among dolphins from the
      Charleston site but did not increase significantly among dolphins from the IRL.
      Dolphins from the Charleston site were more likely to have leukocytosis,
      lymphocytosis, and low serum concentrations of total protein and total J
      globulins than were dolphins from the IRL. CONCLUSIONS AND CLINICAL RELEVANCE:
      High prevalences of diseased dolphins were identified at both sites; however, the
      host or environmental factors that contributed to the various abnormalities
      detected are unknown.

PMID- 18627241
TI  - Evaluation of the function of a type I peritrophic matrix as a physical barrier
      for midgut epithelium invasion by mosquito-borne pathogens in Aedes aegypti.
AB  - In addition to modulating blood meal digestion and protecting the midgut
      epithelial cells from mechanical and chemical damage, a biological function
      attributed to the mosquito type I peritrophic matrix (PM) is preventing or
      reducing pathogen invasion, especially from Plasmodium spp. Previously, we
      demonstrated that chitin is an essential component of the PM and is synthesized
      de novo in response to blood feeding in Aedes aegypti. Therefore, knocking down
      chitin synthase expression by RNA interference severely disrupts formation of the
      PM. Utilizing this artificial manipulation, we determined that the absence of the
      PM has no effect on the development of Brugia pahangi or on the dissemination of
      dengue virus. However, infectivity of Plasmodium gallinaceum is lower, as
      measured by oocyst intensity, when the PM is absent. Our findings also suggest
      that the PM seems to localize proteolytic enzymes along the periphery of the
      blood bolus during the first 24 hours after blood feeding. Finally, the absence
      of the PM does not affect reproductive fitness, as measured by the number and
      viability of eggs oviposited.

PMID- 18627242
TI  - Zooprophylaxis: impact of breeding rabbits around houses on reducing the indoor
      abundance of Phlebotomus papatasi.
AB  - Zooprophylaxis is the use of animals to deviate vectors from humans. The indoor
      abundance of Phlebotomus papatasi in houses with rabbit holes in the peridomestic
      areas are significantly lower than the indoor abundance in houses without rabbit
      holes in their peridomestic areas. Introduction of rabbits in artificial
      underground holes in peridomestic areas reduced significantly the indoor
      abundance of P. papatasi. Cleaning rabbit holes in peridomestic area by removing
      all rabbit feces induced a significant increase in the abundance of P. papatasi
      inside bedrooms. The ecologic niche made around houses in endemic areas by
      creating active rabbit holes is a major source of attractiveness of P. papatasi,
      and therefore it may deviate the vector from humans to rabbits. Although rabbit
      holes are breeding sites for P. papatasi, rabbits are not competent reservoirs
      for Leishmania major. Our overall findings strongly suggest that zooprophylaxis
      could be effective in reducing the indoor abundance of P. papatasi and
      subsequently may be used to control the transmission L. major in rural areas.

PMID- 18627243
TI  - Model for the deposition of aerosol particles in the respiratory tract of the
      rat. I. Nonhygroscopic particle deposition.
AB  - Rats are used to test the toxicological and pharmacological effects of aerosol
      particles on the organism. For estimates of the delivered aerosol dose, lung
      deposition models provide a valuable tool. Here a previously developed deposition
      model for nonhygroscopic and hygroscopic aerosol particles in the lungs of man
      (Ferron et al., J. Aerosol Sci. 1988, 19:611) is adapted to the rat by
      implementing a lung structure for the rat combined with empirical equations for
      particle deposition due to impaction/sedimentation in the extrathoracic region
      and in bifurcations. To account for the effect of body weight (BW) on the
      physiological parameters (lung size, respiration frequency) we present BW-scaling
      laws with an estimated accuracy of about 16%. The present model shows good
      agreement with the measured total deposition (per breath) and other models from
      the literature to within the variability of the experimental data (20% absolute).
      Our calculations show that the variability of the experimental data is consistent
      with the combined effects from realistic variations in particle properties
      (mainly density) and physiological parameters (mainly activity level). For the
      alveolar region, which is of particular significance for pharmacological and
      health studies, we show that although the activity level may change the deposited
      dose by up to a factor of 2.2 for particles between 0.05 and 2.0 microm in
      diameter, the alveolar dose is almost independent (to within 10%) of activity
      level for particles between 0.5 and 1 microm, which makes this size range
      advantageous for pharmacological and toxicological experiments. The present model
      allows estimates of the total and regional particle dose deposited in the lungs
      of rats, which are consistent with experimental data. The advantage of the
      present model is that hygroscopic growth can be included in the calculations.

PMID- 18627244
TI  - Variation in the major surface glycoprotein genes in Pneumocystis jirovecii.
AB  - The genome of Pneumocystis, which causes life-threatening pneumonia in
      immunosuppressed patients, contains a multicopy gene family that encodes the
      major surface glycoprotein (Msg). Pneumocystis can vary the expressed Msg,
      presumably as a mechanism to avoid host immune responses. Analysis of 24 msg-gene
      sequences obtained from a single human isolate of Pneumocystis demonstrated that
      the sequences segregate into 2 branches. Results of a number of analyses suggest
      that recombination between msg genes is an important mechanism for generating msg
      diversity. Intrabranch recombination occurred more frequently than interbranch
      recombination. Restriction-fragment length polymorphism analysis of human
      isolates of Pneumocystis demonstrated substantial variation in the repertoire of
      the msg-gene family, variation that was not observed in laboratory isolates of
      Pneumocystis in rats or mice; this may be the result of examining outbred versus
      captive populations. Increased diversity in the Msg repertoire, generated in part
      by recombination, increases the potential for antigenic variation in this
      abundant surface protein.

PMID- 18627245
TI  - Vaccination with Bacille-Calmette Guerin promotes mycobacterial control in guinea
      pig macrophages infected in vivo.
AB  - Tuberculosis pleurisy was induced by inoculation of virulent (H37Rv strain or
      Erdman strain) or attenuated (H37Ra strain) green-fluorescent protein-expressing
      Mycobacterium tuberculosis into guinea pigs that had or had not been vaccinated
      with Bacille-Calmette Guerin (BCG). Pleural fluid and cells were analyzed for
      phagosome-lysosome (P-L) fusion, on the basis of confocal microscopy,
      intracellular and extracellular bacterial survival, and production of cytokine
      mRNA. BCG vaccination increased fluid volume and cellular accumulation,
      significantly enhanced P-L fusion, and significantly decreased intracellular
      bacterial survival in pleural-effusion macrophages of the guinea pigs infected
      with the 2 virulent strains. Furthermore, significant increases in interferon
      gamma, transforming growth factor-beta, tumor necrosis factor-alpha, and
      interleukin-12p40 cytokine mRNA were seen in the pleural cells of the BCG
      vaccinated guinea pigs.

PMID- 18627246
TI  - Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis.
AB  - The prevalence and molecular characteristics of isolates from 173 immunocompetent
      patients with herpetic keratitis (HK) who were infected with acyclovir (ACV)
      resistant (ACV(R)) corneal herpes simplex virus (HSV)-1 was determined. Isolates
      from 11 (6.4%) of the patients were ACV(R), and 9 of these 11 patients were
      refractory to therapy with ACV; the ACV(R) isolates from 5 and 1 of these 9
      patients were cross-resistant to gancyclovir and to both gancyclovir and
      foscarnet, respectively. Of the 11 ACV(R) isolates, 10 had, in the thymidine
      kinase gene, mutations that presumably conferred the ACV(R) phenotype. These data
      demonstrate a relatively high prevalence of corneal HSV-1 ACV(R) isolates in
      patients with HK, which emphasizes the need to monitor for ACV susceptibility in
      patients with HK who are refractory to therapy with ACV.

PMID- 18627247
TI  - An internal polyadenylation signal substantially increases expression levels of
      lentivirus-delivered transgenes but has the potential to reduce viral titer in a
      promoter-dependent manner.
AB  - In lentiviral gene delivery systems, transgene expression cassettes are commonly
      cloned without a polyadenylation signal to prevent disruption of full-length
      lentiviral genomes on mRNA maturation in producer cells. The lack of the
      polyadenylation signal, however, has the potential to reduce stability and
      translation efficiency of transgene mRNA. Therefore, we have assessed the effect
      of a strong internal polyadenylation [poly(A)] signal on both transgene
      expression levels in virus-infected cells and functional viral titer, in a series
      of eight self-inactivating lentiviruses expressing the mOrange transgene under
      the control of the constitutive cytomegalovirus (CMV), elongation factor 1alpha
      (EF1alpha), and beta-actin promoters or the highly tissue-specific prostate
      specific antigen/probasin hybrid (PSA/Pb) promoter with or without a simian virus
      40 (SV40) early polyadenylation signal downstream of the mOrange-coding sequence.
      We show that mOrange expression levels in virus-infected HEK-293, LNCaP, and
      primary prostate epithelial cells were increased 3- to 6.5-fold when an internal
      polyadenylation signal was present. When the CMV and EF1alpha promoters were
      used, functional viral titer decreased 8- to 9-fold in the presence of the
      polyadenylation signal, but titer was not affected when transgene expression was
      driven by the beta-actin promoter or tissue-specific PSA/Pb promoter. We
      therefore conclude that an internal polyadenylation signal in lentiviral vectors
      has a highly beneficial effect on transgene expression, but reduces viral titer
      in a promoter-dependent manner.

PMID- 18627248
TI  - Changing epidemiology of invasive pneumococcal disease: a complicated story.

PMID- 18627249
TI  - Changing epidemiology of invasive pneumococcal disease among White Mountain
      Apache persons in the era of the pneumococcal conjugate vaccine.
AB  - BACKGROUND: Prior to the introduction of the 7-valent pneumococcal conjugate
      vaccine (PCV7), the rate of invasive pneumococcal disease (IPD) was 8-fold higher
      among White Mountain Apache persons of all ages than it was among the general US
      population, . We aimed to assess the impact of PCV7 and 23-valent pneumococcal
      polysaccharide vaccine on the rate of IPD among White Mountain Apache persons.
      METHODS: From 1991 through 2006, we conducted active laboratory- and population
      based surveillance among Native American residents of the White Mountain Apache
      reservation. Charts were reviewed and pneumococcal isolates were collected for
      serotype testing. Three time periods were defined: the pre-PCV7 baseline period
      (1991-1997), the PCV7 efficacy trial period (1998-2000), and the PCV7 routine-use
      period (2001-2006). RESULTS: We identified 246 cases of IPD; the mean annual IPD
      rate fell from 126 cases per 100,000 person-years in the period 1991-1997 to 87
      cases per 100,000 person-years in the period 2001-2006 (p = .01). The rate of IPD
      attributable to PCV7 serotypes of Streptococcus pneumoniae decreased by 252 cases
      per 100,000 person-years (92%) among children aged <5 years, and that
      attributable to non-PCV7 serotypes of S. pneumoniae decreased by 87 cases per
      100,000 person-years (44%) among children aged <5 years. Among adults, the rate
      of IPD remained unchanged; PCV7 serotypes of S. pneumoniae accounted for only 25%
      of adult cases during the period 1991-1997. CONCLUSIONS: Since the introduction
      of PCV7, the rate of IPD among White Mountain Apache children aged <5 years has
      decreased to the lowest rate ever (122 cases per 100,000 person-years), but it
      remains 5.7-fold greater than the rate of IPD among children in the general US
      population. In contrast to some other high-risk populations, there is no evidence
      of non-vaccine-type replacement disease in this age group. Among White Mountain
      Apache adults, the rate of IPD remains substantially higher than that observed in
      the general US population. Vaccines with broader serotype coverage are needed to
      further reduce the disparity in the rate of IPD between the White Mountain Apache
      and general US populations.

PMID- 18627250
TI  - Effect of cervical cytologic status on the association between human
      papillomavirus type 16 DNA load and the risk of cervical intraepithelial
      neoplasia grade 3.
AB  - BACKGROUND: Although correlations between cervical cytologic status and both
      human papillomavirus (HPV) load and histopathologic status are recognized, it is
      largely undetermined whether the association between the HPV DNA load and the
      risk of cervical intraepithelial neoplasia grade 3 (CIN-3) differs on the basis
      of cervical cytologic findings. METHODS: Study subjects were 821 women enrolled
      in the ASCUS-LSIL Triage Study who tested positive for HPV-16 at entry. Women
      were followed semiannually for 2 years. The baseline HPV-16 load was measured by
      real-time polymerase chain reaction. RESULTS: CIN-3 was confirmed in 286 (34.8%)
      of 821 women during the 2-year follow-up period. The adjusted odds ratio (OR) of
      the 2-year cumulative risk of CIN-3 was 1.46 (95% confidence interval [CI], 1.29
      1.64) per 1 log(10) increase in virus load. The ORs varied from 1.66 (95% CI,
      1.16-2.37) for women with normal cytologic findings at enrollment to 0.86 (95%
      CI, 0.61-1.20) for those with high-grade squamous intraepithelial lesions. Among
      women with normal cytologic findings at enrollment, the area under the receiver
      operating characteristic curve for detection of CIN-3 on the basis of the virus
      load was 0.70 (95% CI, 0.61-0.78). CONCLUSION: The HPV-16 DNA load was associated
      with the risk of developing CIN-3, but the associations varied with cytologic
      findings at the time of virus load measurement. The clinical usefulness of
      measuring the HPV-16 load as a means to detect CIN-3 was minimal, even in women
      with normal cytologic findings.

PMID- 18627251
TI  - The classification of traumatic brain injury (TBI) for targeted therapies.

PMID- 18627253
TI  - Changes of cerebral blood flow during the secondary expansion of a cortical
      contusion assessed by 14C-iodoantipyrine autoradiography in mice using a non
      invasive protocol.
AB  - Although changes of cerebral blood flow (CBF) in and around traumatic contusions
      are well documented, the role of CBF for the delayed death of neuronal cells in
      the traumatic penumbra ultimately resulting in secondary contusion expansion
      remains unclear. The aim of the current study was therefore to investigate the
      relationship between changes of CBF and progressive peri-contusional cell death
      following traumatic brain injury (TBI). CBF and contusion size were measured in
      C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min
      and 24 h following controlled cortical impact by 14C-iodoantipyrine
      autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively.
      Contused and ischemic (CBF < 10%) tissue volumes were calculated and compared
      over time. Cortical CBF in not injured mice varied between 69 and 93 mL/100mg/min
      depending on the anatomical location. Fifteen minutes after trauma, CBF decreased
      in the whole brain by approximately 50% (39 +/- 18 mL/100mg/min; p < 0.05),
      except in contused tissue where it fell by more than 90% (3 +/- 2 mL/100mg/min; p
      < 0.001). Within 24 h after TBI, CBF recovered to normal values in all brain
      areas except the contusion where it remained reduced by more than 90% (p <
      0.001). Contusion volume expanded from 24.9 to 35.5 mm3 (p < 0.01) from 15 min to
      24 h after trauma (+43%), whereas the area of severe ischemia (CBF < 10%) showed
      only a minimal (+13%) and not significant increase (22.3 to 25.1 mm3). The
      current data therefore suggest that the delayed secondary expansion of a cortical
      contusion following traumatic brain injury may not be caused by a reduction of
      CBF alone.

PMID- 18627252
TI  - Classification of traumatic brain injury for targeted therapies.
AB  - The heterogeneity of traumatic brain injury (TBI) is considered one of the most
      significant barriers to finding effective therapeutic interventions. In October,
      2007, the National Institute of Neurological Disorders and Stroke, with support
      from the Brain Injury Association of America, the Defense and Veterans Brain
      Injury Center, and the National Institute of Disability and Rehabilitation
      Research, convened a workshop to outline the steps needed to develop a reliable,
      efficient and valid classification system for TBI that could be used to link
      specific patterns of brain and neurovascular injury with appropriate therapeutic
      interventions. Currently, the Glasgow Coma Scale (GCS) is the primary selection
      criterion for inclusion in most TBI clinical trials. While the GCS is extremely
      useful in the clinical management and prognosis of TBI, it does not provide
      specific information about the pathophysiologic mechanisms which are responsible
      for neurological deficits and targeted by interventions. On the premise that
      brain injuries with similar pathoanatomic features are likely to share common
      pathophysiologic mechanisms, participants proposed that a new, multidimensional
      classification system should be developed for TBI clinical trials. It was agreed
      that preclinical models were vital in establishing pathophysiologic mechanisms
      relevant to specific pathoanatomic types of TBI and verifying that a given
      therapeutic approach improves outcome in these targeted TBI types. In a clinical
      trial, patients with the targeted pathoanatomic injury type would be selected
      using an initial diagnostic entry criterion, including their severity of injury.
      Coexisting brain injury types would be identified and multivariate prognostic
      modeling used for refinement of inclusion/exclusion criteria and patient
      stratification. Outcome assessment would utilize endpoints relevant to the
      targeted injury type. Advantages and disadvantages of currently available
      diagnostic, monitoring, and assessment tools were discussed. Recommendations were
      made for enhancing the utility of available or emerging tools in order to
      facilitate implementation of a pathoanatomic classification approach for clinical
      trials.

PMID- 18627254
TI  - Disruption of Bax protein prevents neuronal cell death but produces cognitive
      impairment in mice following traumatic brain injury.
AB  - Apoptosis contributes to delayed neuronal cell death in traumatic brain injury
      (TBI). To investigate if Bax plays a role in neuronal cell death and functional
      outcome after TBI, Bax gene disrupted (null) mice and wild-type (WT) controls
      were subjected to the controlled cortical impact (CCI) model of TBI. Motor
      function in WT and Bax null mice was evaluated using the round beam balance and
      the wire grip test on days 0-5. Spatial memory was assessed using a Morris Water
      Maze adopted for mice on days 14-18 post-injury. For histopathological analysis,
      animals were sacrificed 24 h and 21 days post-injury. In all three behavioral
      tests, the sham and TBI-injured Bax null mice performed significantly worse than
      their WT sham and TBI-injured counterparts. However, Bax null mice exhibited a
      higher percentage of surviving neurons in the CA1 and CA3 regions of hippocampus
      measured at 21 days post-injury. At 24 h after trauma, Bax null mice had fewer
      TUNEL positive cells in the CA1 and dentate regions of hippocampus as compared to
      WT mice, suggesting that deletion of the Bax gene ameliorates hippocampal cell
      death after TBI. Sham-operated Bax null mice had significantly greater brain
      volume as compared to WT mice. Thus, it is possible that Bax deficiency in the
      transgenic mice produces developmental behavioral effects, perhaps due to Bax's
      role in regulating cell death during development.

PMID- 18627256
TI  - Selection of endogenous control genes for normalization of gene expression
      analysis after experimental brain trauma in mice.
AB  - Quantitative measurements of gene expression require correction for tissue sample
      size, RNA quantity, and reverse transcription efficiency. This can be achieved by
      normalization with control genes. The study was designed to identify candidates
      not altered after brain trauma. Male C57Bl/6 mice were anesthetized with
      isoflurane, and a pneumatic brain trauma was induced by controlled cortical
      impact (CCI) on the right parietal cortex. Brains were removed at 15 min, and 3,
      6, 12 and 24 h after CCI and from naive animals (n = 6 each). Absolute copies of
      six control genes (beta-2-microglobin [B2M], cyclophilin A, beta-actin,
      hypoxanthine ribosyltransferase [HPRT], porphobilinogen deaminase [PBGD], and
      glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) and one example target gene
      (iNOS) were determined by real-time reverse transcription-polymerase chain
      reaction (RT-PCR; Lightcycler) in the traumatic focus and contralateral tissue.
      Control gene expression was stable until 12 h after CCI. At 24 h after CCI
      expression of B2M, cyclophilin A and HPRT remained stable in the contusion, while
      expression of beta-actin, GAPDH, and PBGD increased. Due to variations between
      animals (+/-85%), increases in beta-actin (+64%) and GAPDH (+59%) did not reach
      the level of significance. In non-contused tissue, expression of all genes
      dropped 24 h after CCI (range, -17% to -61%). Due to low variations between
      animals and stable expression after CCI, B2M and cyclophilin A seem to be
      suitable to serve as single normalizer. Normalization of the example target gene
      iNOS resulted in varying relative expression extending from onefold (PBDG) to 10
      fold (HPRT). The results suggest that the knowledge of the temporal profile of
      control genes is essential to properly interpret results of mRNA quantification.

PMID- 18627255
TI  - Agrin expression during synaptogenesis induced by traumatic brain injury.
AB  - Interaction between extracellular matrix proteins and regulatory proteinases can
      mediate synaptic integrity. Previously, we documented that matrix
      metalloproteinase 3 (MMP-3) expression and activity increase following traumatic
      brain injury (TBI). We now report protein and mRNA analysis of agrin, a MMP-3
      substrate, over the time course of trauma-induced synaptogenesis. Agrin
      expression during the successful synaptic reorganization of unilateral entorhinal
      cortical lesion (UEC) was compared with expression when normal synaptogenesis
      fails (combined fluid percussion TBI and bilateral entorhinal lesion [BEC]). We
      observed that agrin protein was increased in both models at 2 and 7 days
      postinjury, and immuohistochemical (IHC) co-localization suggested reactive
      astrocytes contribute to that increase. Agrin formed defined boundaries for
      sprouting axons along deafferented dendrites in the UEC, but failed to do so
      after combined insult. Similarly, Western blot analysis revealed greater increase
      in UEC agrin protein relative to the combined TBI+BEC model. Both models showed
      increased agrin transcription at 7 days postinjury and mRNA normalization by 15
      days. Attenuation of synaptic pathology with the NMDA antagonist MK-801 reduced 7
      day UEC agrin transcript to a level not different from unlesioned controls. By
      contrast, MK-801 in the combined insult failed to significantly change 7-day
      agrin transcript, mRNA levels remaining elevated over uninjured sham cases.
      Together, these results suggest that agrin plays an important role in the
      sprouting phase of reactive synaptogenesis, and that both its expression and
      distribution are correlated with extent of successful recovery after TBI.
      Further, when pathogenic conditions which induce synaptic plasticity are reduced,
      increase in agrin mRNA is attenuated.

PMID- 18627257
TI  - Finite element analysis of spinal cord injury in the rat.
AB  - A three-dimensional (3D) finite element model (FEM) that simulates the Impactor
      weight-drop experimental model of traumatic spinal cord injury (SCI) was
      developed. The model consists of the rat spinal cord, with distinct element sets
      for the gray and white matter, the cerebrospinal fluid (CSF), the dura mater, a
      rigid rat spinal column, and a rigid impactor. Loading conditions were taken from
      the average impact velocities determined from previous parallel weight-drop
      experiments employing a 2.5-mm-diameter, 10-g rod dropped from either 12.5 or 25
      mm. The mechanical properties were calibrated by comparing the predicted
      displacement of the spinal cord at the impact site to that measured
      experimentally. Parametric studies were performed to determine the sensitivity of
      the model to the relevant material properties, loading conditions, and essential
      boundary conditions, and it was determined that the shear modulus had the
      greatest influence on spinal cord displacement. Additional simulations were
      performed where gray and white matter were prescribed different material
      properties. These simulations generated similar drop trajectories to the
      homogeneous model, but the stress and strain distributions better matched
      patterns of acute albumin extravasation across the blood-spinal cord barrier
      following weight-drop SCI, as judged by a logit analysis. A final simulation was
      performed where the impact site was shifted laterally by 0.35 mm. The off-center
      impact had little effect on the rod trajectory, but caused marked shifts in the
      location of stress and strain contours. Different combinations of parameter
      values could reproduce the impactor trajectory, which suggests that another
      experimental measure of the tissue response is required for validation. The FEM
      can be a valuable tool for understanding the injury biomechanics associated with
      experimental SCI to identify areas for improvement in animal models and future
      research to identify thresholds for injury.

PMID- 18627258
TI  - Contrasting biomechanics and neuropathology of spinal cord injury in neonatal and
      adult rats following vertebral dislocation.
AB  - Clinically, spinal cord injuries (SCI) in infants are different from SCIs in
      adults. SCI is rarer in infants, and the most common types of associated spinal
      column injury are different for adults and infants. Initially, infants tend to
      have higher injury severities and mortality; however, young survivors of SCI
      typically have greater and more rapid functional recovery. The objective of this
      study was to contrast the biomechanics and neuropathology of SCI in adult and
      neonatal rats to investigate these differences. Thoracolumbar vertebrae of
      anaesthetized rats were dislocated laterally (T12 held stationary and L1
      displaced laterally, with T13 between these levels) by 10 mm at 250 mm/sec in
      adults and by 4 mm at 100 mm/sec in neonates (13-15 days), and rats were
      euthanized 6 h later. Spinal cord sections were stained to detect hemorrhage
      (with hematoxylin and eosin [H&E]), axonal injury (with beta-amyloid precursor
      protein [betaAPP]), and neuronal nuclei (with NeuN). Maximum load was
      significantly higher in adults (25.7 +/- 2.4N) than neonates (11.0 +/- 2.4N; p <
      0.001). Adult and neonatal hemorrhage volumes were not significantly different
      for either the raw or normalized data sets (p = 0.064 for normalized dataset). Un
      normalized axonal injury densities were similar for adults and neonates, but
      normalized axonal injury density was significantly higher in neonates (p <
      0.001). Reduction of NeuN immunoreactivity was significantly lower in neonates,
      for both un-normalized (p < 0.004) and normalized (p < 0.001) data sets. The
      findings of this study may explain the different common types of spinal column
      injury associated with SCI, and the greater initial severity of SCI in infants.

PMID- 18627259
TI  - Intraspinal MDL28170 microinjection improves functional and pathological outcome
      following spinal cord injury.
AB  - Although calpain (calcium-activated cysteine protease) inhibition represents a
      rational therapeutic target for spinal cord injury (SCI), few studies have
      reported improved functional outcomes with post-injury administration of calpain
      inhibitors. This reflects the weak potency and limited aqueous solubility of
      current calpain inhibitors. Previously, we demonstrated that intraspinal
      microinjection of the calpain inhibitor MDL28170 resulted in greater inhibition
      of calpain activity as compared to systemic administration of the same compound.
      In the present study, we evaluated the ability of intraspinal MDL28170
      microinjection to spare spinal tissue and locomotor dysfunction following SCI.
      Contusion SCI was produced in female Long-Evans rats using the Infinite Horizon
      impactor at the 200-kdyn force setting. Open-field locomotion was evaluated until
      6 weeks post-injury. Histological assessment of tissue sparing was performed at 6
      weeks after SCI. The results demonstrate that MDL28170, administered with a
      single post-injury intraspinal microinjection (50 nmoles), significantly improves
      both locomotor function and pathological outcome measures following SCI.

PMID- 18627260
TI  - Hypothermia reduces cytotoxic edema and metabolic alterations during the acute
      phase of massive SAH: a diffusion-weighted imaging and spectroscopy study in
      rats.
AB  - Acute changes in cerebral perfusion and metabolism after subarachnoid hemorrhage
      (SAH) have been shown to contribute significantly to acute brain injury. The
      purpose of this study was to examine the effects of moderate hypothermia on the
      acute changes after massive experimental SAH as evaluated by diffusion-weighted
      imaging (DWI) and magnetic resonance spectroscopy (MRS). SAH in rats was induced
      by injection of 0.5 mL of arterial blood. Normothermic animals (NT, n = 10) were
      kept at 37.0 +/- 0.2 degrees C, while temperature was lowered to 32.0 +/- 0.2
      degrees C in the primary hypothermia group (pHT, n = 10) prior to SAH and in the
      secondary hypothermia group (sHT, n = 10) immediately after SAH. DWI and MRS were
      performed from 30 min prior up to 3 h after injury. The apparent diffusion
      coefficient (ADC) was measured in cortical and hippocampal regions of interest
      (ROIs). MRS included lactate, N-acetyl aspartate (NAA), and creatine in a central
      voxel. DWI showed a generalized, significant decline in ADC after SAH in NT.
      Significant change in ADC in pHT was absent, and accelerated recovery for animals
      in sHT was noted. MRS analysis revealed significant lactate accumulation to 204
      +/- 40% from baseline only in NT, while sHT was characterized by a transient,
      less pronounced increase of lactate (159 +/- 11%) and lactate in pHT did not
      change significantly (117 +/- 11%). NAA did not change significantly when
      compared to baseline or between groups for NT, pHT, or sHT. Creatine rose
      significantly to 166 +/- 27% in NT after the insult, indicating increased
      metabolic stress which was absent in pHT (106 +/- 8%) and sHT (124 +/- 18%).
      Hypothermia can ameliorate early development of cytotoxic edema, lactate
      accumulation, and a general metabolic stress response after SAH, even when
      started after the insult. Our study indicates that a potentially beneficial
      influence on metabolism and cerebral perfusion in this crucial phase is
      practicable and might hold the key to further improve outcome in SAH.

PMID- 18627263
TI  - Ephs and ephrins: a new way for bone cells to communicate.

PMID- 18627264
TI  - EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in
      differentiating osteoblasts.
AB  - With the aim of identifying new pathways and genes regulated by PTH(1-34) and PTH
      related protein 1-141 [PTHrP(1-141)] in osteoblasts, this study was carried out
      using a mouse marrow stromal cell line, Kusa 4b10, that acquires features of the
      osteoblastic phenotype in long-term culture conditions. After the appearance of
      functional PTH receptor 1 (PTHR1) in Kusa 4b10 cells, they were treated with
      either PTH(1-34) or PTHrP(1-141), and RNA was subjected to Affymetrix whole mouse
      genome array. The microarray data were validated using quantitative real-time RT
      PCR on independently prepared RNA samples from differentiated Kusa 4b10, UMR106
      osteosarcoma cells, and primary mouse calvarial osteoblasts, as well as in vivo
      using RNA from metaphyseal bone after a single PTH injection to 3-wk-old and 6-mo
      old ovariectomized rats. Of the 45,101 probes used on the microarray, 4675 were
      differentially expressed by >or=1.5 fold, with a false discovery rate <0.1. Among
      the regulated genes, ephrinB2 mRNA was upregulated in response to both PTH and
      PTHrP. This was confirmed by quantitative real-time PCR in vitro and in vivo.
      Increased ephrinB2 protein was also shown in vitro by Western blotting, and
      immunostaining of femur sections showed ephrinB2 in both osteoclasts and
      osteoblasts. Production of ephrinB2, as well as other ephrins or Eph family
      members, did not change during differentiation of Kusa 4b10 cells. Blockade of
      ephrinB2/EphB4 interaction resulted in inhibition of mineralization of Kusa 4b10
      cells. Together with the shown effect of ephrinB2 promoting osteoblast
      differentiation and bone formation through action on EphB4, the data raise the
      possibility that PTH or PTHrP might regulate ephrinB2 to act in a paracrine or
      autocrine manner on EphB4 or EphB2 in the osteoblast, contributing as a local
      event to the anabolic action of PTH or PTHrP.

PMID- 18627265
TI  - Calcitonin receptor plays a physiological role to protect against hypercalcemia
      in mice.
AB  - It is well established that calcitonin is a potent inhibitor of bone resorption;
      however, a physiological role for calcitonin acting through its cognate receptor,
      the calcitonin receptor (CTR), has not been identified. Data from previous
      genetically modified animal models have recognized a possible role for calcitonin
      and the CTR in controlling bone formation; however, interpretation of these data
      are complicated, in part because of their mixed genetic background. Therefore, to
      elucidate the physiological role of the CTR in calcium and bone metabolism, we
      generated a viable global CTR knockout (KO) mouse model using the Cre/loxP
      system, in which the CTR is globally deleted by >94% but <100%. Global CTRKOs
      displayed normal serum ultrafiltrable calcium levels and a mild increase in bone
      formation in males, showing that the CTR plays a modest physiological role in the
      regulation of bone and calcium homeostasis in the basal state in mice.
      Furthermore, the peak in serum total calcium after calcitriol [1,25(OH)(2)D(3)]
      induced hypercalcemia was substantially greater in global CTRKOs compared with
      controls. These data provide strong evidence for a biological role of the CTR in
      regulating calcium homeostasis in states of calcium stress.

PMID- 18627266
TI  - Effects of intravenous zoledronate on bone turnover and BMD persist for at least
      24 months.
AB  - The duration of the antiresorptive effects of the intravenous bisphosphonate,
      zoledronate, is not known. Recently, we reported that two annual 4-mg doses of
      zoledronate suppressed bone turnover and increased BMD in HIV-infected men over
      24 mo. We set out to determine the persistence of these effects after two doses
      of zoledronate. Thirty-three HIV-infected men who completed a randomized trial of
      4 mg annual zoledronate (n = 17) or placebo (n = 16) were studied for a further
      12 mo, during which time no skeletal therapy was administered. Participants
      received calcium (400 mg/d) and vitamin D supplements (50,000 IU/mo) for the
      first 24 mo of the study only. Biochemical markers of bone turnover and BMD were
      measured every 6 mo. Bone turnover markers were stably suppressed at 24 and 36 mo
      (12 and 24 mo after the second annual dose of zoledronate, respectively). There
      were no significant within-group changes in urine N-telopeptide, serum C
      telopeptide, and osteocalcin between 24 and 36 mo (p > 0.07), and at each time
      point, each of the turnover markers was significantly lower in the zoledronate
      group. There were also no significant between-group differences in the changes in
      BMD at each site between 24 and 36 mo (p > 0.5), and at each time point, BMD at
      each site was significantly higher in the zoledronate group. These results
      suggest that the antiresorptive effects of zoledronate last >12 mo and raise the
      possibility that zoledronate could be administered less frequently than annually.
      Randomized trials that address this issue should be performed.

PMID- 18627267
TI  - Replacement of native adenovirus receptor-binding sites with a new attachment
      moiety diminishes hepatic tropism and enhances bioavailability in mice.
AB  - The in vivo efficacy of adenoviral vectors (AdVs) in gene delivery strategies is
      hampered by the broad tissue tropism of the virus and its efficient binding to
      human erythrocytes. To circumvent these limitations, we developed a prototype AdV
      lacking native binding sites. We replaced the adenoviral fiber with a chimeric
      molecule consisting of the fiber tail domain, the reovirus sigma1 oligomerization
      domain, and a polyhistidine tag as model targeting moiety. We also abolished the
      integrin-binding motif in the penton base protein. The chimeric attachment
      molecule was efficiently incorporated onto AdV capsids, allowed efficient
      propagation of AdV without requirement for complementing fiber and conferred
      highly specific tropism to the AdV. Importantly, the targeted AdV exhibited
      markedly reduced tropism for liver cells. In comparison with control AdV with
      native tropism, the targeted AdV showed 1000-fold reduced transduction of HepG2
      cells and 10,000-fold reduced transduction of mouse liver cells in freshly
      isolated liver slices. After intravenous inoculation of C57BL/6 mice, the
      targeted AdV exhibited delayed clearance in comparison with the native AdV,
      leaving approximately 10-fold greater levels in the blood 2 hr after inoculation.
      For all tissues analyzed, the targeted AdV displayed significantly reduced in
      vivo transduction in comparison with the native vector. Furthermore, in contrast
      to the native AdV, the targeted AdV did not bind human erythrocytes. Together,
      our findings suggest that the targeted AdV design described here provides a
      promising platform for systemic in vivo gene delivery.

PMID- 18627269
TI  - A new humanized mouse model of Epstein-Barr virus infection that reproduces
      persistent infection, lymphoproliferative disorder, and cell-mediated and humoral
      immune responses.
AB  - The functional human immune system, including T, B, and natural killer
      lymphocytes, is reconstituted in NOD/Shi-scid/IL-2Rgamma(null) (NOG) mice that
      receive hematopoietic stem cell transplants. Here, we show that these humanized
      mice can recapitulate key aspects of Epstein-Barr virus (EBV) infection in
      humans. Inoculation with approximately 1 x 10(3) TD(50) (50% transforming dose)
      of EBV caused B cell lymphoproliferative disorder, with histopathological
      findings and latent EBV gene expression remarkably similar to that in
      immunocompromised patients. Inoculation with a low dose of virus (<or=1 x 10(1)
      TD(50)), in contrast, resulted in apparently asymptomatic persistent infection.
      Levels of activated CD8(+) T cells increased dramatically in the peripheral blood
      of infected mice, and enzyme-linked immunospot assay and flow cytometry
      demonstrated an EBV-specific T cell response. Immunoglobulin M antibody specific
      to the EBV-encoded protein BFRF3 was detected in serum from infected mice. The
      NOG mouse is the most comprehensive small-animal model of EBV infection described
      to date and should facilitate studies of the pathogenesis, prevention, and
      treatment of EBV infection.

PMID- 18627270
TI  - Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV
      infected men: a prospective cohort study.
AB  - Outbreaks of acute hepatitis C virus (HCV) infection are occurring in HIV
      infected men who have sex with men. We evaluated risk factors and liver
      histopathology in 11 consecutively enrolled men with newly acquired HCV infection
      that was diagnosed on the basis of antibody seroconversion, new elevations in
      alanine aminotransferase level, and wide fluctuations in HCV RNA level. Ten
      patients reported unprotected anal intercourse, and 7 reported "club-drug" use,
      including methamphetamine. Liver biopsy showed moderately advanced fibrosis
      (Scheuer stage 2) in 9 patients (82%). No cause of liver damage other than acute
      HCV infection was identified. The specific pathways leading to periportal
      fibrosis in HIV-infected men with newly acquired HCV infection require
      investigation.

PMID- 18627268
TI  - Aging and infectious diseases: workshop on HIV infection and aging: what is known
      and future research directions.
AB  - Highly active antiretroviral treatment has resulted in dramatically increased
      life expectancy among patients with HIV infection who are now aging while
      receiving treatment and are at risk of developing chronic diseases associated
      with advanced age. Similarities between aging and the courses of human
      immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome
      suggest that HIV infection compresses the aging process, perhaps accelerating
      comorbidities and frailty. In a workshop organized by the Association of
      Specialty Professors, the Infectious Diseases Society of America, the HIV Medical
      Association, the National Institute on Aging, and the National Institute on
      Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics,
      immunology, and gerontology met to review what is known about HIV infection and
      aging, to identify research gaps, and to suggest high priority topics for future
      research. Answers to the questions posed are likely to help prioritize and
      balance strategies to slow the progression of HIV infection, to address
      comorbidities and drug toxicity, and to enhance understanding about both HIV
      infection and aging.

PMID- 18627271
TI  - Experimental expansion of the regulatory T cell population increases resistance
      to African trypanosomiasis.
AB  - Inflammatory responses mounted to eliminate parasites can be lethal if not
      counterbalanced by regulatory responses protecting the host from collateral
      tissue damage. Here, we show that the maintained inflammation associated with
      tissue damage, anemia, and reduced survival of Trypanosoma brucei-infected mice
      correlates with the absence of the expansion of the regulatory T (T(reg)) cell
      population. Induction of T(reg) cell expansion via CD28 superagonist antibody
      treatment in these mice down-regulated interferon-gamma production by T cells and
      tumor necrosis factor-alpha and reactive oxygen species production by classically
      activated macrophages, triggered the development of alternatively activated
      macrophages, delayed the onset of liver injury, diminished the anemia burden, and
      prolonged the survival of infected animals. Thus, triggering the expansion of the
      T(reg) cell population coupled with the induction of alternatively activated
      macrophages can restore the balance between pro- and anti-inflammatory signals
      and thereby limit the pathogenicity of African trypanosomiasis.

PMID- 18627272
TI  - Deficiency of alpha7 cholinergic receptors facilitates bacterial clearance in
      Escherichia coli peritonitis.
AB  - BACKGROUND: The efferent vagus nerve can inhibit inflammation via interaction
      between acetylcholine and alpha7 cholinergic receptors. METHODS: To determine the
      role played by alpha7 receptors in antibacterial defense, peritonitis was induced
      in alpha7 receptor-deficient (alpha7(-/-)) and wild-type (WT) mice by
      intraperitoneal injection with Escherichia coli. RESULTS: At 20 h after
      infection, virtually all alpha7(-/-) mice had cleared the infection from their
      peritoneal cavities and had sterile blood cultures, whereas WT mice had high
      bacterial loads at the primary site of infection and were bacteremic. In
      addition, bacterial burdens in liver, spleen, kidneys, and lungs were much lower
      in alpha7(-/-) mice, and these animals displayed a diminished inflammatory
      response, as reflected by a reduced number of infiltrating neutrophils in
      peritoneal lavage fluid and lower circulating cytokine levels. At 2 h after
      infection, however, when bacterial loads were still similar in alpha7(-/-) and WT
      mice, the former mouse strain showed a more robust influx of neutrophils into the
      peritoneal cavity. CONCLUSIONS: Deficiency of the alpha7 receptor is associated
      with an accelerated clearance of E. coli after intraperitoneal infection,
      preceded by a faster recruitment of neutrophils. These data provide the first
      evidence for a detrimental role of alpha7 receptors in the host defense against
      bacteria.

PMID- 18627273
TI  - Role of nitric oxide in defense of the central nervous system against
      Mycobacterium tuberculosis.
AB  - Murine models of tuberculous meningitis (TBM) have not reflected the severity of
      disease in humans. Based on reports that activated murine microglial cells, but
      not human microglial cells, express inducible nitric oxide synthase (iNOS), the
      objective of this study was to determine whether iNOS-knockout (iNOS(-/-)) mice
      would provide such a model. iNOS(-/-) mice infected with M. tuberculosis
      developed serious clinical manifestations and granulomatous lesions containing
      tubercle bacilli throughout the meninges, all of which were absent in wild-type
      mice. This study underscores the importance of nitric oxide in defense against
      TBM and suggests that iNOS(-/-) mice are an appropriate model for human TBM.

PMID- 18627274
TI  - Anti-inflammatory effect from indomethacin nanoparticles inhaled by male mice.
AB  - The respiratory system provides entry for drug nanoparticles to cure systemic
      diseases. The modern devices that are available on the market of therapeutic
      aerosol delivery systems have a number of disadvantages. There remains a need for
      an alternative means that is low cost, convenient, and capable of producing small
      sized particles. On the other hand, one-third of the modern drugs are poorly
      water soluble. Many currently available injectable formulations of such drugs can
      cause side effects that originate from detergents and other agents used for their
      solubilization. The aerosol lung administration may by a good way for delivery of
      the water-insoluble drugs. We present here a new way for the generation of drug
      nanoparticles suitable for many water insoluble substances based on the
      evaporation-condensation route. In this paper the indomethacin nanoaerosol
      formation was studied and its anti-inflammatory effect to the outbred male mice
      was examined. The evaporation-condensation aerosol generator consisted of a
      horizontal cylindrical quartz tube with an outer heater. Argon flow was supplied
      to the inlet and the aerosol was formed at the outlet. The particle mean diameter
      and number concentration were varied in the ranges 3 to 200 nm and 10(3) to 10(7)
      cm(-3), respectively. The liquid chromatography and X-ray diffraction methods
      have shown the nanoparticles consist of the amorphous phase indomethacin. The
      aerosol lung administration experiments were carried out in the whole-body
      exposure chamber. Both the lung deposited dose and the particle deposition
      efficiency were determined as a function of the mean particle diameter for mice
      being housed into the nose-only exposure chambers. The anti-inflammatory action
      and side pulmonary effects caused by the inhalation of indomethacin nanoparticles
      were investigated. It was found that the aerosol administration was much more
      effective than the peroral treatment. The aerosol route required a therapeutic
      dose six orders of magnitude less than that for peroral administration.

PMID- 18627275
TI  - Family experiences with pediatric antiretroviral therapy: responsibilities,
      barriers, and strategies for remembering medications.
AB  - This study examines the relationship between adherence to pediatric HIV regimens
      and three family experience factors: (1) regimen responsibility; (2) barriers to
      adherence; and (3) strategies for remembering to give medications. Caregivers of
      127 children ages 2-15 years in the PACTS-HOPE multisite study were interviewed.
      Seventy-six percent of caregivers reported that their children were adherent
      (taking > or = 90% of prescribed doses within the prior 6 months). Most
      caregivers reported taking primary responsibility for medication-related
      activities (72%-95% across activities); caregivers with primary responsibility
      for calling to obtain refills (95%) were more likely to have adherent children.
      More than half of caregivers reported experiencing one or more adherence barriers
      (59%). Caregivers who reported more barriers were also more likely to report
      having non-adherent children. Individual barriers associated with nonadherence
      included forgetting, changes in routine, being too busy, and child refusal. Most
      reported using one or more memory strategies (86%). Strategy use was not
      associated with adherence. Using more strategies was associated with a greater
      likelihood of reporting that forgetting was a barrier. For some families with
      adherence-related organizational or motivational difficulties, using numerous
      memory strategies may be insufficient for mastering adherence. More intensive
      interventions, such as home-based nurse-administered dosing, may be necessary.

PMID- 18627276
TI  - Prevalence and incidence of sexually transmitted infections among South Indians
      at increased risk of HIV infection.
AB  - Sexually transmitted infections (STIs) have been identified as cofactors of HIV
      transmission. Greater understanding of local STI burdens can assist in the
      development of more effective STI and HIV prevention strategies. The aim of this
      study is to determine the prevalence and incidence of STIs among South Indian men
      and women identified to be at increased risk for HIV infection. Individuals at
      increased risk for HIV infection were enrolled in a prospective longitudinal
      study in Chennai, India (n = 480) between August 2002 and December 2003.
      Participants were enrolled from patients seeking services at an sexually
      transmitted disease (STD) clinic and a confidential HIV testing and counseling
      program. The most common prevalent STIs were herpes simplex virus (HSV)-2 (50% of
      women, 29% of men), syphilis (11% of women, 8% of men), and Trichomonas vaginalis
      (6% of women). At enrollment, women, participants with no schooling, participants
      with greater than four sex partners, and single participants were found to be at
      increased risk for HSV-2 infection (p < 0.05). The two most common incident STIs
      at 12 months were HSV-2 with 12% of men and 8% of women testing positive and
      hepatitis B with 2% of men and 5% of women testing hepatitis B surface antigen
      (HBsAg) positive. In this cohort of South Indian men and women with a high
      background prevalence of HSV-2, suppressive therapy against herpes replication
      may have a substantial impact in reducing both HSV-2 transmission and HIV
      acquisition. With the high incidence of STIs, targeted prevention and clinical
      management strategies among individuals practicing high risk behaviors may help
      to slow the continued spread of HIV in India.

PMID- 18627277
TI  - Antifungal effect of mouth rinses on oral Candida counts and salivary flow in
      treatment-naive HIV-infected patients.
AB  - Oral candidiasis is a major problem in developing countries where antiretroviral
      therapy is available to a small percentage of the infected population. HIV
      patients are prone to xerostomia and predisposed to Candida infection. Preventing
      oral candidiasis is better than the frequent use of antifungals that may lead to
      the development of drug resistance. This study investigated the ability of
      commercial mouth rinses and sodium bicarbonate to reduce salivary Candida and to
      improve the saliva flow of HIV-positive patients. One hundred fifty HIV patients
      without oral candidiasis were examined for oral lesions initially and after 2, 4,
      and 12 weeks. Unstimulated saliva was collected; the volume was measured and
      cultured for yeasts. Subjects were provided with mouth rinses containing either
      benzydamine hydrochloride, benzydamine hydrochloride with chlorhexidine
      gluconate, triclosan with sodium fluoride, 5% sodium bicarbonate, or placebo and
      asked to rinse twice daily for 12 weeks. The effect of the mouth rinses and
      placebo on Candida counts and saliva flow was analyzed using analysis of variance
      (ANOVA). A total of 108 patients completed the trial, 35 missed appointments, 4
      died, 2 developed oral candidiasis, and 1 herpetic lesion. Triclosan/fluoride
      decreased the Candida count more than the placebo (p = 0.005) while
      chlorhexidine/benzydamine hydrochloride (p = 0.001) and triclosan/fluoride
      mouthrinses (p = 0.002) increased the salivary flow during the initial 4 weeks.
      The most effective mouth rinse triclosan/fluoride decreased oral Candida counts
      and increased saliva flow. Studies are needed to determine the efficacy of these
      mouth rinses for the long-term prevention of clinical oral candidiasis in adult
      HIV-positive patients.

PMID- 18627278
TI  - Diffuse intra-abdominal granulomatous seeding as a manifestation of immune
      reconstitution inflammatory syndrome associated with microsporidiosis in a
      patient with HIV.

PMID- 18627279
TI  - A qualitative examination of the indirect effects of modified directly observed
      therapy on health behaviors other than adherence.
AB  - Modified directly observed therapy (mDOT), in which a portion of doses in a
      medication regimen are ingested under supervision, has had some demonstrated
      success in improving the high levels of adherence necessary to achieve maximum
      benefit from antiretroviral medications. Consistent with the Information
      Motivation-Behavioral skills (IMB) model, mDOT's success is likely due to its
      direct impact on patients' knowledge, motivation, and behaviors related to
      adherence. However, mDOT's potential impact on patients' information, motivation,
      and behaviors related to health activities other than adherence to antiretroviral
      medications has not been explored. Data from participants enrolled in Project
      MOTIV8, a randomized controlled trial to test the efficacy of novel behavioral
      adherence interventions, were analyzed to explore the potential impact of mDOT on
      health behaviors other than adherence. Participants were recruited from local HIV
      clinics from 2004-2008. Thirty-four percent of those approached, agreed to
      participate in the study. Data from all participants randomized to the mDOT
      intervention arm thus far (n = 50, mean age 39.7 standard deviation [SD] = 9.0,
      78% male 64% African American, and 86% infected via sexual transmission) were
      included. Overall, participants reported a high level of satisfaction with the
      mDOT intervention. Qualitative data revealed that mDOT had a positive impact on
      participants' adherence to nonantiretroviral medications as well as their
      involvement and communication with health care providers. In addition,
      participants reported that the daily mDOT visits had indirect effects on their
      daily functioning, including improvements in their daily living activities (e.g.,
      earlier awakenings, getting dressed, and cleaning their homes) and an increased
      level of community involvement.

PMID- 18627280
TI  - Implementation and evaluation of a clinic-based behavioral intervention: positive
      steps for patients with HIV.
AB  - We conducted a demonstration project to design, implement, and evaluate a risk
      reduction intervention delivered by medical providers to patients with HIV during
      routine care in 2005 and 2006. Medical providers at seven HIV clinics in the
      United States received training to deliver an intervention in which they screened
      patients for behavioral risks, gave targeted counseling, and delivered prevention
      messages. A longitudinal cohort (n = 767) of patients completed a baseline
      questionnaire and two follow-up questionnaires (6-month intervals) after the
      intervention was initiated. Logistic regression and generalized estimating
      equations (GEE) methods were used in analyses. The cohort had a median age of 41,
      was 58% black, 28% white, and 10% Hispanic; 32% were women and 42% self
      identified as men who have sex with men. The 3-month prevalence of unprotected
      anal or vaginal intercourse (UAVI) with any partners declined significantly (p <
      0.001) from baseline (42%) to follow-up (26% at first follow-up, 23% at second
      follow-up). The decline was significant with partners who were HIV
      negative/unknown serostatus or HIV-positive. Cohort patients' self-reported
      receipt of safer-sex counseling at all, some, or no clinic visits during the
      interval between baseline and first follow-up showed a dose-response relationship
      with decline in prevalence of UAVI in that interval, with relative reductions of
      45%, 35%, and 19%, respectively. All findings were confirmed in multivariate
      models that controlled for demographic factors and HIV clinical status of
      participants. This project demonstrated that with only brief training, HIV
      medical providers successfully conducted an HIV prevention intervention with
      their clinic patients. Our findings indicate that clinics that serve HIV patients
      can incorporate such programs as standard of care.

PMID- 18627281
TI  - HIV provider perspectives: the impact of stigma on substance abusers living with
      HIV in a rural area of the United States.
AB  - Recent literature has documented growing concerns related to access to HIV care
      services for rural individuals living with both HIV and a dual diagnosis of
      substance abuse. Previous research has investigated issues from a client
      perspective, but limited research has investigated provider perspectives of rural
      issues surrounding HIV and substance abuse. The purpose of this qualitative study
      was to examine issues that impact the ability of care providers to create
      sustainable linkages to care for dual diagnosed individuals who live in rural
      areas. In-depth interviews were conducted in late 2005 with 39 HIV service
      providers at 11 agencies that provided HIV-related services to individuals in
      rural areas of a Midwestern state in the United States. Findings suggest
      multidimensional stigma in the medical referral network as the leading factor
      that presents challenges to service providers in rural areas. The service
      providers reported verbal stigma in the form of insults, a loss of role/respect,
      and a global loss of resources such as poorer quality health care or no health
      care provided. The stigma is conceptualized in four themes: (1) staff of medical
      referral sources stigmatizing against rural dual-diagnosis clients, (2)
      physicians stigmatizing against rural dual-diagnosis clients, (3) medical
      specialists stigmatizing against rural dual-diagnosis clients, and (4) client
      perceived stigma. These themes were expressed equally among all of the providers,
      regardless of geographic location, type of HIV-related organization, or job
      title.

PMID- 18627282
TI  - HIV screening among U.S. physicians, 1999-2000.
AB  - In 2006, the Centers for Disease Control and Prevention (CDC) put forth
      recommendations for routine HIV screening for all individuals aged 13-64. The
      frequency and correlates of HIV screening among U.S. physicians in 2000 were
      examined to provide baseline data for evaluating the implementation of the 2006
      CDC HIV testing guidelines through a survey mailed to a random sample of U.S.
      physicians in the American Medical Association's Masterfile. The primary outcome
      was self-reported HIV screening of asymptomatic male and nonpregnant female
      patients. A total of 4133 (adjusted completion rate of 70.2%) returned a
      completed survey. Overall, 1133 (28.4%) of physicians reported HIV screening.
      U.S. physicians, who were female, black, Hispanic, practiced in a city of more
      than 250,000 people, diagnosed HIV in the past 2 years, or followed up with
      patients to see if they notified their sexual partners, were more likely to
      screen their patients for HIV. Emergency medicine, internal medicine, and
      pediatrics specialists were less likely to screen than family/general
      practitioners. In 2000, only a quarter of U.S. physicians reported screening
      their patients for HIV and these rates varied by physician characteristics and
      practice settings.

PMID- 18627283
TI  - Participation in HIV research: the importance of clinic contact factors.
AB  - Recruiting minority populations living with HIV to many types of clinic-based HIV
      research is a concern. This study examined an expanded range of predictors of HIV
      research participation (clinic contact, clinical, and personal characteristics)
      to investigate observed ethnocultural differences in HIV research participation.
      Research participation was defined as participation in any of diagnostic,
      pathogenesis, drug trial or survey research. Logistic regression modeling was
      used to predict research participation of 657 eligible patients (93% of the
      patient population) who began care between January 1997 and the end of September
      2003 at a regional outpatient HIV care program in Calgary, Canada. Approximately
      one third (32%) were non-white, including 18% Aboriginal, 9% black, 4% Asian, and
      1% Hispanic individuals. Twenty-nine percent (187/657) of the patients
      participated in at least one study of any kind. Multivariate analysis indicated
      that the strongest predictors of any research participation (including
      diagnostic, pathogenesis, drug trial, or survey studies) are clinical (including
      nadir CD4 count [odds ratio {OR} = 0.132, p < 0.05] and antiretroviral medication
      [OR = 3.041, p < 0.01]), and clinic contact characteristics (years in treatment
      [OR = 1.949, p < .05], and percentage of appointments kept [OR = 1.022, p <
      .05]). Few personal characteristics were related to research participation-only
      reported injection drug use (OR = 0.363, p < 0.05), and birth year (OR = 0.968, p
      = 0.054) were significantly or marginally related to research participation.
      There was no significant difference among ethnocultural groups (white, non
      white). Results thus suggest that much of the variation in research participation
      associated with ethnocultural group or race is accounted for by clinic contact
      variables. This in turn suggests that it is the different patterns of clinical
      interactions and service use shown by these groups that may influence research
      participation. To attract under researched populations, attention should shift
      from the "who" of research participation to the "how" of clinical interactions.

PMID- 18627284
TI  - The DLC-1 -29A/T polymorphism is not associated with nasopharyngeal carcinoma
      risk in Chinese population.
AB  - Deleted in liver cancer-1 (DLC-1), encoding a Rho GTPase-activating protein
      (GAP), is considered as a promising candidate tumor suppressor gene in
      nasopharyngeal carcinoma (NPC). The single-nucleotide polymorphism (SNP) -29A/T
      upstream of ATG start codon was found when gene mutation profile of DLC-1 in NPC
      was analyzed. To evaluate the correlation between SNP -29A/T in the promoter
      region of DLC-1 gene and risk of NPC, a total of 521 samples from a Chinese
      population, including 320 healthy individuals and 201 NPC patients, were
      collected for SNP analysis by PCR-single-strand conformation polymorphism and
      sequencing. The differences in allele and genotype frequencies between NPC
      patients and controls were tested using logistic regression statistical method.
      No significant differences were found in allele or genotype frequencies between
      NPC patients and controls or among different NPC clinical stages. Hence, our data
      indicate that the SNP -29A/T of DLC-1 gene is not associated with NPC
      susceptibility.

PMID- 18627285
TI  - Complement factor H variant p.Y402H in pseudoxanthoma elasticum patients.
AB  - Pseudoxanthoma elasticum (PXE) is a hereditary disorder predominantly affecting
      the eyes, the skin, and the vascular system. The subretinal neovascularization
      and retinal hemorrhages leading to the loss of central vision in PXE are similar
      to the process observed in age-related macular degeneration (AMD). The complement
      factor H (CFH) variant c.1277T > C (p.Y402H) is a recently discovered risk factor
      for AMD. The aim of this study was to analyze whether this CFH variant is a
      secondary genetic risk factor for PXE. Therefore, the genotypes of CFH c.1277T >
      C (p.Y402H) were determined in 189 German PXE patients and 189 age- and sex
      matched controls. The allelic frequencies of the investigated variant did not
      differ between patients and controls. The frequencies were 33%, 56%, and 11% for
      wild-type, heterozygous, and homozygous genotypes in the PXE patients and 36%,
      51%, and 13% in the control cohort, respectively. Further, no significant
      associations were identified when allele carriers were analyzed or after
      adjustment for sex, age, smoking, organ involvement, hypertension, or age at
      disease onset. No significant genotype-phenotype correlation was detected. In
      conclusion, our data reliably show that the CFH variant c.1277T > C (p.Y402H) is
      not a genetic risk factor for PXE.

PMID- 18627286
TI  - Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate
      expressed tryptic proteinases as regulators of signalling via proteinase
      activated receptors (PARs).
AB  - The prostate is a site of high expression of serine proteinases including members
      of the kallikrein-related peptidase (KLK) family, as well as other secreted and
      membrane-anchored serine proteinases. It has been known for some time that
      members of this enzyme family elicit cellular responses by acting directly on
      cells. More recently, it has been recognised that for serine proteinases with
      specificity for cleavage after arginine and lysine residues (trypsin-like or
      tryptic enzymes) these cellular responses are often mediated by cleavage of
      members of the proteinase-activated receptor (PAR) family--a four member sub
      family of G protein-coupled receptors. Here, we review the expression of PARs in
      prostate, the ability of prostatic trypsin-like KLKs and other prostate-expressed
      tryptic enzymes to cleave PARs, as well as the prostate cancer-associated
      consequences of PAR activation. In addition, we explore the dysregulation of
      trypsin-like serine proteinase activity through the loss of normal inhibitory
      mechanisms and potential interactions between these dysregulated enzymes leading
      to aberrant PAR activation, intracellular signalling and cancer-promoting
      cellular changes.

PMID- 18627288
TI  - Development of diabetic cardiomyopathy and the kallikrein-kinin system--new
      insights from B1 and B2 receptor signaling.
AB  - Diabetic cardiomyopathy is a specific cardiomyopathy which develops in patients
      with diabetes mellitus in the absence of coronary atherosclerosis and
      hypertension. Despite the potential importance of this disease entity, the
      underlying mechanisms are only incompletely understood. Changes in calcium
      handling, disruption of the extracellular matrix regulation with accumulation of
      cardiac collagen, and furthermore cardiac inflammation may be an important
      mediator of this disease. This brief review focuses on the current aspects of the
      kallikrein-kinin system and its influence on the development of diabetic
      cardiomyopathy with particular regard to the kinin receptors B1 and B2, as their
      role in the development of this disease is still under discussion. Whether the
      role of the B1 receptor is similar to the well-described beneficial role of the
      B2 receptor or whether its function is opposed to the B2 receptor is
      controversial. Some recent findings suggest that the B1 receptor mediates cardiac
      inflammation and therefore may be detrimental for cardiac function in the setting
      of diabetic cardiomyopathy.

PMID- 18627287
TI  - Functions of KLK4 and MMP-20 in dental enamel formation.
AB  - Two proteases are secreted into the enamel matrix of developing teeth. The early
      protease is enamelysin (MMP-20). The late protease is kallikrein 4 (KLK4).
      Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis
      imperfecta, a condition featuring soft, porous enamel containing residual
      protein. MMP-20 is secreted along with enamel proteins by secretory-stage
      ameloblasts. Enamel protein-cleavage products accumulate in the space between the
      crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated
      enamel proteins, so their concentration decreases with depth. KLK4 is secreted by
      transition- and maturation-stage ameloblasts. KLK4 aggressively degrades the
      retained organic matrix following the termination of enamel protein secretion.
      The principle functions of MMP-20 and KLK4 in dental enamel formation are to
      facilitate the orderly replacement of organic matrix with mineral, generating an
      enamel layer that is harder, less porous, and unstained by retained enamel
      proteins.

PMID- 18627289
TI  - Kallikreins as microRNA targets: an in silico and experimental-based analysis.
AB  - microRNAs (miRNAs) are non-coding RNAs that target specific mRNAs. They have been
      shown to control many biological processes including cancer pathogenesis.
      Kallikreins (KLKs) are a family of serine proteases that are attracting interest
      as cancer biomarkers. The mechanism of regulation of kallikrein expression is
      largely unknown. We investigated the potential roles of miRNAs in regulating KLK
      expression. Using a bioinformatics approach, we identified 96 strong KLK/miRNA
      interactions. KLK10 is the most frequently targeted kallikrein, followed by KLK5
      and KLK13. KLK1, KLK3, KLK8 and KLK12 do not have strongly predicted miRNA/KLK
      interactions. Ten miRNAs are predicted to target more than one KLK. KLK2, KLK4,
      KLK5 and KLK10 have multiple miRNA-targeting sites on their transcript.
      Chromosomes 19 and 14 harbor significantly more KLK-targeting miRNAs. Many KLK
      targeting miRNAs have been shown to be dysregulated in malignancy. We
      experimentally verified our bioinformatics data for the let-7f miRNA in a cell
      line model. let-7f transfection led to a significant decrease in secreted KLK6
      and KLK10 protein levels. Co-transfection of let-7f and anti-let-7f inhibitor was
      able to partially rescue these protein levels. We conclude that miRNAs play a
      role in the regulation of KLK expression. Further studies are needed to
      investigate whether this regulation is altered in cancer.

PMID- 18627291
TI  - Immunofluorometric activity-based probe analysis of active KLK6 in biological
      fluids.
AB  - Immunoassay measurements of human kallikrein-related peptidases (KLKs) such as
      prostate-specific antigen (KLK3) are of great value as diagnostic indices of
      cancer. Despite extensive knowledge of the abundance of immunoreactive KLKs in
      normal and cancer-related settings, there is little information available about
      the proportion of immunoreactive KLK that represents active enzyme in such
      samples. Using KLK6 as a prototype enzyme, we have developed an assay using a
      serine proteinase-targeted activity-based probe coupled to antibody capture. By
      employing activity-based labeling, we were able to quantify the proportion of
      enzymatically active relative to total immunoreactive KLK6 in crude cerebrospinal
      fluid from routine analyses and ascites fluid from ovarian cancer patients, as
      well as in supernatants from cancer cell lines. Our approach allowed monitoring
      of pro-KLK6 conversion to its active enzyme species and demonstrated that up to
      5% of immunoreactive KLK6 detected in clinical samples represents active enzyme.
      We suggest that this new activity-based probe assay will prove of value as a
      complement to routine KLK immunoassay measurements for validating KLKs as cancer
      biomarkers.

PMID- 18627290
TI  - Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells.
AB  - Kallikrein 6 (KLK6) is a trypsin-like serine peptidase whose relevance in various
      types of cancers is currently being explored. Previous studies have shown that
      KLK6 mRNA is upregulated in colon and gastric cancers; however, the regulatory
      mechanisms and phenotypic consequences of this upregulation are largely unknown.
      Activating K-RAS mutations are common in colon cancer, occurring in approximately
      50% of cases. We have recently reported the upregulation of KLK6 mRNA in Caco2
      human colon cancer cells stably transfected with a mutant K-RAS allele (K
      RAS(G12V)). In this study we examined the pattern of K-RAS-dependent KLK6
      expression and secretion in colon cancer cells. Using pharmacological inhibitors
      of pathways downstream of K-RAS, we could show that the PI3K and p42/44 MAPK
      pathways play an important role in the induction of KLK6 in mutant K-RAS
      expressing colon cancer cells. Increased KLK6 expression enhanced colon cancer
      cell migration through laminin and Matrigel. Inhibition of KLK6 using small
      interference RNA treatment or a specific KLK6 antibody in Caco2 cells stably
      expressing the mutant K-RAS and in SW480 cells carrying a mutation in the K-RAS
      oncogene resulted in a reduction in invasiveness through cell culture inserts.
      These data support the oncogenic role of KLK6 in colorectal cancer.

PMID- 18627292
TI  - Gene expression changes associated with the anti-angiogenic activity of
      kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells.
AB  - Kallikrein-related peptidase 3 (KLK3, also known as prostate-specific antigen,
      PSA) is a chymotrypsin-like kallikrein that has anti-angiogenic properties. We
      have previously shown in a human umbilical vein endothelial cell (HUVEC) model
      that the anti-angiogenic effect of KLK3 is related to its enzyme activity.
      However, the mechanism of this effect remains to be clarified. To this end, we
      used a DNA microarray to study KLK3-induced changes in gene expression associated
      with reduction of HUVEC tube formation. Among the 41,000 genes studied, 311 were
      differentially expressed between control and KLK3-treated cells. These changes
      were enriched in several pathways, including those associated with proteasome,
      ubiquitin-mediated proteolysis, focal adhesion and regulation of the actin
      cytoskeleton. Furthermore, the changes were opposite to those previously
      described to occur during tubulogenesis. In conclusion, our results show that
      KLK3 induces gene expression changes in HUVECs. Although these changes might be
      relevant for the mechanism by which KLK3 exerts its anti-angiogenic activity, it
      cannot be judged from the present results whether they reflect the primary
      mechanism mediating the effect of KLK3 or are secondary to morphogenic
      differentiation.

PMID- 18627293
TI  - Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial
      infarction in a kininogen-deficient rat model.
AB  - Bradykinin (BK) coronary outflow and left ventricular (LV) performance of
      kininogen-deficient Brown Norway Katholiek (BNK) rats and Brown Norway Hannover
      (BNH) controls were investigated. We analyzed whether the angiotensin-converting
      enzyme (ACE) inhibitor ramipril is able to attenuate LV dysfunction after
      induction of myocardial infarction (MI) in this animal model. Ex vivo, the basal
      BK content in the coronary outflow of buffer-perfused, isolated hearts was
      measured by specific radioimmunoassay. In vivo, left ventricular pressure (LVP),
      the maximal rate of LVP increase, LV end-diastolic pressure, the maximal rate of
      LVP decrease and heart rate were determined using a tip catheter 3 weeks after
      induction of MI. Compared to BNK rats, basal BK outflow was increased 30-fold in
      controls (p<0.01). In vivo, we found no significant differences between sham
      ligated BNK and BNH rats in basal LV function. After MI, the impairment of LV
      function was significantly worse in BNK rats when compared to BNH rats. ACE
      inhibition significantly attenuated this LV dysfunction in both groups, when
      compared to untreated animals. Reduced basal BK level resulting from kininogen
      deficiency has no effect on basal LV function, but remains to be a risk factor
      for the ischemic heart. However, ACE inhibition is sufficient to improve LV
      function despite kininogen deficiency.

PMID- 18627294
TI  - Tissue kallikrein and kinin infusion promotes neovascularization in limb
      ischemia.
AB  - Adenovirus-mediated kallikrein delivery has been shown to promote blood vessel
      growth in the limb under both ischemic and normoperfused conditions. Here we
      investigated whether a continuous supply of kallikrein and kinin peptide can
      induce neovascularization in a rat model of hindlimb ischemia. Rats underwent
      femoral artery ligation and localized injection of tissue kallikrein, bradykinin
      or B1 receptor agonist, followed by infusion of proteins by osmotic minipump.
      Regional blood flow was monitored weekly by laser Doppler perfusion imaging.
      Three weeks after surgery, rats receiving kallikrein and kinins showed a
      significant increase in the perfusion ratio of ischemic vs. normoperfused limb
      compared to control rats. Similarly, a microsphere assay showed that kallikrein
      and kinins significantly increased regional blood flow without altering blood
      pressure. Moreover, kallikrein and kinins significantly augmented capillary and
      arteriole densities, as quantified by immunostaining with CD-31 and smooth muscle
      alpha-actin. Both tissue kallikrein and bradykinin increased hemoglobin content
      in Matrigel implants in mice, providing further evidence of the angiogenic
      properties. Kinins, when delivered subcutaneously via Matrigel in rats, also
      increased regional perfusion. This is the first demonstration that local
      application of tissue kallikrein protein or kinin peptide has therapeutic value
      in the treatment of ischemic disease by promoting neovascularization.

PMID- 18627295
TI  - Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by
      gene deletion of the kinin B1 receptor.
AB  - Clinical use of the anthracycline doxorubicin (DOX) is limited by its cardiotoxic
      effects, which are attributed to the induction of apoptosis. To elucidate the
      possible role of the kinin B1 receptor (B1R) during the development of DOX
      cardiomyopathy, we studied B1R knockout mice (B1R(-/-)) by investigating cardiac
      inflammation and apoptosis after induction of DOX-induced cardiomyopathy. DOX
      control mice showed cardiac dysfunction measured by pressure-volume loops in
      vivo. This was associated with a reduced activation state of AKT, as well as an
      increased bax/bcl2 ratio in Western blots, indicating cardiac apoptosis.
      Furthermore, mRNA levels of the proinflammatory cytokine interleukin 6 were
      increased in the cardiac tissue. In DOX B1R(-/-) mice, cardiac dysfunction was
      improved compared to DOX control mice, which was associated with normalization of
      the bax/bcl-2 ratio and interleukin 6, as well as AKT activation state. These
      findings suggest that B1R is detrimental in DOX cardiomyopathy in that it
      mediates the inflammatory response and apoptosis. These insights might have
      useful implications for future studies utilizing B1R antagonists for treatment of
      human DOX cardiomyopathy.

PMID- 18627296
TI  - Kallikreins and proteinase-mediated signaling: proteinase-activated receptors
      (PARs) and the pathophysiology of inflammatory diseases and cancer.
AB  - Proteinases such as thrombin and trypsin can affect tissues by activating a novel
      family of G protein-coupled proteinase-activated receptors (PARs 1-4) by exposing
      a 'tethered' receptor-triggering ligand (TL). Work with synthetic TL-derived PAR
      peptide sequences (PAR-APs) that stimulate PARs 1, 2 and 4 has shown that PAR
      activation can play a role in many tissues, including the gastrointestinal tract,
      kidney, muscle, nerve, lung and the central and peripheral nervous systems, and
      can promote tumor growth and invasion. PARs may play roles in many settings,
      including cancer, arthritis, asthma, inflammatory bowel disease,
      neurodegeneration and cardiovascular disease, as well as in pathogen-induced
      inflammation. In addition to activating or disarming PARs, proteinases can also
      cause hormone-like effects via PAR-independent mechanisms, such as activation of
      the insulin receptor. In addition to proteinases of the coagulation cascade,
      recent data suggest that members of the family of kallikrein-related peptidases
      (KLKs) represent endogenous PAR regulators. In summary: (1) proteinases are like
      hormones, signaling in a paracrine and endocrine manner via PARs or other
      mechanisms; (2) KLKs must now be seen as potential hormone-like PAR regulators in
      vivo; and (3) PAR-regulating proteinases, their target PARs, and their associated
      signaling pathways appear to be novel therapeutic targets.

PMID- 18627298
TI  - A potential role for tissue kallikrein-related peptidases in human cervico
      vaginal physiology.
AB  - Human tissue kallikrein-related peptidases (KLK) are a family of 15 genes located
      on chromosome 19q13.4 that encode secreted serine proteases with trypsin- and/or
      chymotrypsin-like activity. Relatively large levels of many KLKs are present in
      human cervico-vaginal fluid (CVF) and in the supernatant of cultured human
      vaginal epithelial cells. Many KLKs are also hormonally regulated in vaginal
      epithelial cells, particularly by glucocorticoids and estrogens. The
      physiological role of KLK in the vagina is currently unknown; however, analysis
      of the CVF proteome has revealed clues for potential KLK functions in this
      environment. Here, we detail potential roles for KLKs in cervico-vaginal
      physiology. First, we suggest that KLKs play a role in the vagina similar to
      their role in skin physiology: (1) in the desquamation of vaginal epithelial
      cells, similar to their activity in the desquamation of skin corneocytes; and (2)
      in their ability to activate antimicrobial proteins in CVF as they do in sweat.
      Consequently, we hypothesize that dysregulated KLK expression in the vagina could
      lead to the development of pathological conditions such as desquamative
      inflammatory vaginitis. Second, we propose that KLKs may play a role in premature
      rupture of membranes and pre-term birth through their cleavage of fetal membrane
      extracellular matrix proteins.

PMID- 18627299
TI  - Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier
      functions.
AB  - Human tissue kallikreins (KLKs) are the largest family of secreted serine
      protease endopeptidases encoded by 15 genes clustered on chromosome 19q13.4.
      Multiple KLK enzymes are co-localized in the upper stratum granulosum and stratum
      corneum of human epidermis, and in associated appendages such as hair follicle
      epithelia and sweat glands. Until recently, kallikrein proteolytic activity in
      the skin was exclusively attributed to KLK5 and KLK7. However, wider cutaneous
      roles of kallikreins became evident in recent years as the proposal of KLK
      proteolytic activation cascades emerged. We postulate that these proteolytic
      enzymes may serve as promiscuous mediators of different skin barrier functions,
      since they are capable of proteolysing different substrates that govern skin
      desquamation, antimicrobial defense, and lipid permeability. Growing evidence now
      attests to potential kallikrein involvement in skin inflammation, pigmentation,
      and tumor suppression via their ability to target proteinase-activated receptor
      signaling pathways. Current knowledge on kallikrein roles in skin physiology and
      pathobiology is described in this review.

PMID- 18627302
TI  - Quantitative RT-PCR analysis and immunohistochemical localization of the
      kallikrein-related peptidases 13 and 14 in lung.
AB  - Expression of the KLK13 and KLK14 genes was examined at the mRNA and protein
      levels in a cohort of 57 patients with non-small-cell lung cancer (NSCLC). The
      mRNA levels, assessed by real-time RT-PCR, were significantly different in
      malignant tissues compared to adjacent non-malignant tissues (KLK13, p=0.006;
      KLK14, p=0.022). KLK13 and KLK14 mRNA overexpression in tumors (1/3 of the
      patients) was associated with a positive nodal status in multivariate analysis
      (p=0.018 and p=0.069, respectively). KLK13 and KLK14 were localized in the
      cytoplasm of epithelial cells of normal bronchus and NSCLC, as determined by
      immunohistochemistry. Moreover, positive staining was significantly associated
      with adenocarcinoma histotype (KLK13, p=0.014) and tumor size (KLK14, p=0.048).
      Although the results are marginally significant, patients with high KLK13
      expression at the mRNA or protein level had lower overall survival.

PMID- 18627300
TI  - Kallikreins are associated with secondary progressive multiple sclerosis and
      promote neurodegeneration.
AB  - Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a
      subfamily of serine proteases that have defined or proposed roles in a range of
      central nervous system (CNS) and non-CNS pathologies. To further understand their
      potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and
      10 were determined in 35 MS patients and 62 controls by quantitative fluorometric
      ELISA. Serum levels were then correlated with Expanded Disability Status Scale
      (EDSS) scores determined at the time of serological sampling or at last clinical
      follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients
      (p<or=0.027), with highest levels associated with secondary progressive disease.
      Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and
      KLK6 with future EDSS worsening in relapsing remitting patients (p<or=0.007).
      Supporting the concept that KLK1 and KLK6 promote degenerative events associated
      with progressive MS, exposure of murine cortical neurons to either kallikrein
      promoted rapid neurite retraction and neuron loss. These novel findings suggest
      that KLK1 and KLK6 may serve as serological markers of progressive MS and
      contribute directly to the development of neurological disability by promoting
      axonal injury and neuron cell death.

PMID- 18627303
TI  - Genetic deficiency in tissue kallikrein activity in mouse and man: effect on
      arteries, heart and kidney.
AB  - Tissue kallikrein (KLK1) is a kinin-forming serine protease synthesized in many
      organs including arteries and kidney. Study of the physiological role of KLK1 has
      benefited from the availability of mouse and human genetic models of KLK1
      deficiency, through engineering of KLK1 mouse mutants and discovery of a major
      polymorphism in the human KLK1 gene that induces a loss of enzyme activity.
      Studies in KLK1-deficient mice and human subjects partially deficient in KLK1
      have documented its critical role in arterial function in both species. KLK1 is
      also involved in the control of ionic transport in the renal tubule, an action
      that may not be kinin-mediated. Studies of experimental diseases in KLK1
      deficient mice have revealed cardio- and nephro-protective effects of KLK1 and
      kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes.
      Potential clinical and therapeutic developments are discussed.

PMID- 18627304
TI  - An AKT activity threshold regulates androgen-dependent and androgen-independent
      PSA expression in prostate cancer cell lines.
AB  - The androgen receptor (AR) plays an important role in early prostate cancer by
      activating transcription of a number of genes participating in cell proliferation
      and growth and cancer progression. However, as the cancer progresses, prostate
      cancer cells transform from an androgen-dependent to an androgen-independent
      state. Androgen-independent prostate cancer can manifest itself in several forms,
      including a percentage of cancers that show reduced levels of prostate-specific
      antigen (PSA) and can progress without the need for the ligand or active
      receptor. Therefore, our goal was to examine the role of intracellular signaling
      pathways in an androgen-independent prostate cancer in vitro model. Using the
      cell line PC3(AR)(2), we stimulated cells with 5-alpha-dihydrotestosterone (DHT)
      and epidermal growth factor (EGF) and then analyzed PSA expression. We observed
      lower PSA expression when cells were jointly stimulated with DHT and EGF, and
      this was associated with an increase in AKT activity. We examined the role of AKT
      in AR activity and PSA expression by creating stable PC3(AR)(2) cell lines
      transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower
      DHT-stimulated PSA expression that correlated to changes in the phosphorylated
      state of AR. Therefore, we propose an in vitro androgen-independent model in
      which a PI3K/AKT activity threshold and subsequent AR transactivation regulate
      PSA expression.

PMID- 18627305
TI  - microRNAs: a new frontier in kallikrein research.
AB  - microRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that
      regulate gene expression. Rapidly accumulating evidence has revealed that miRNAs
      are associated with cancer. The human tissue kallikrein gene family is the
      largest contiguous family of proteases in the human genome, containing 15 genes.
      Many kallikreins have been reported as potential tumor markers. In this review,
      recent bioinformatics and experimental evidence is presented indicating that
      kallikreins are potential miRNA targets. The available experimental approaches to
      investigate these interactions and the potential diagnostic and therapeutic
      applications are also discussed. miRNAs represent a possible regulatory mechanism
      for controlling kallikrein expression at the post-transcriptional level. Many
      miRNAs were predicted to target kallikreins and a single miRNA can target more
      than one kallikrein. Recent evidence suggests that miRNAs can also exert
      'quantitative' control of kallikreins by utilizing multiple targeting sites in
      the kallikrein mRNA. More research is needed to experimentally verify the in
      silico predictions and to investigate the possible role in tumor initiation
      and/or progression.

PMID- 18627306
TI  - Adult progenitor cells in vascular remodeling during atherosclerosis.
AB  - The mobilization and recruitment of bone marrow-derived, circulating or tissue
      resident progenitor cells giving rise to smooth muscle-like cells have been
      implicated in neointima hyperplasia after arterial injury and in accelerated
      forms of arterial lesion formation, e.g., transplant arteriopathy or graft
      vasculopathy. By contrast, convincing evidence has emerged that the vascular
      homing of endothelial progenitor cells (EPCs) contributes to endothelial
      recovery, thus limiting neointima formation after arterial injury. In the chronic
      context of primary atherosclerosis, plaque progression and destabilization, a
      more complex picture has become apparent. In patients with coronary artery
      disease, the number and function of EPCs have been linked with an improved
      endothelial function or regeneration, but have been inversely correlated with
      cardiovascular risk. In animal models, however, the injection of bone marrow
      cells or EPCs, or the application of stem-cell mobilizing factors, have been
      associated with an exacerbation of atherosclerosis and unstable plaque
      phenotypes, whereas the contribution of bone marrow-derived smooth muscle
      progenitors to primary atherosclerosis appears to be rather confined. Here, we
      discuss crucial biochemical cues, namely chemokines, adhesion molecules, growth
      factors and pharmacological means that guide and control the context-specific
      mobilization, recruitment and fate of vascular progenitor cells in arterial
      remodeling during atherosclerosis.

PMID- 18627307
TI  - In vitro differentiation of reprogrammed murine somatic cells into hepatic
      precursor cells.
AB  - Recently, a new approach to reprogram somatic cells into pluripotent stem cells
      was shown by fusion of somatic cells with embryonic stem (ES) cells, which
      results in a tetraploid karyotype. Normal hepatocytes are often polyploid, so we
      decided to investigate the differentiation potential of fusion hybrids into
      hepatic cells. We chose toxic milk mice (a model of Wilson's disease) and
      performed initial transplantation experiments using this potential cell therapy
      approach. Mononuclear bone marrow cells from Rosa26 mice were fused with OG2
      (Oct4-GFP transgenic) ES cells. Unfused ES cells were eliminated by selection
      with G418 for OG2-Rosa26 hybrids and fusion-derived colonies could be subcloned.
      Using an endodermal differentiation protocol, hepatic precursor cells could be
      generated. After FACS depletion of contaminating Oct4-GFP-positive cells, the
      hepatic precursor cells were transplanted into immunosuppressed toxic milk mice
      by intrasplenic injection. However, five out of eight mice showed teratoma
      formation within 3-6 weeks after transplantation in the spleen and liver. In
      conclusion, a hepatic precursor cell type was achieved from mononuclear bone
      marrow cell-ES cell hybrids and preliminary transplantation experiments confirmed
      engraftment, but also showed teratoma formation, which needs to be excluded by
      using more stringent purification strategies.

PMID- 18627308
TI  - Bone marrow-derived mesenchymal stem cell transplantation does not improve
      quality of muscle reinnervation or recovery of motor function after facial nerve
      transection in rats.
AB  - Recently, we devised and validated a novel strategy in rats to improve the
      outcome of facial nerve reconstruction by daily manual stimulation of the target
      muscles. The treatment resulted in full recovery of facial movements (whisking),
      which was achieved by reducing the proportion of pathologically polyinnervated
      motor endplates. Here, we posed whether manual stimulation could also be
      beneficial after a surgical procedure potentially useful for treatment of large
      peripheral nerve defects, i.e., entubulation of the transected facial nerve in a
      conduit filled with suspension of isogeneic bone marrow-derived mesenchymal stem
      cells (BM-MSCs) in collagen. Compared to control treatment with collagen only,
      entubulation with BM-MSCs failed to decrease the extent of collateral axonal
      branching at the lesion site and did not improve functional recovery. Post
      operative manual stimulation of vibrissal muscles also failed to promote a better
      recovery following entubulation with BM-MSCs. We suggest that BM-MSCs promote
      excessive trophic support for regenerating axons which, in turn, results in
      excessive collateral branching at the lesion site and extensive polyinnervation
      of the motor endplates. Furthermore, such deleterious effects cannot be
      overridden by manual stimulation. We conclude that entubulation with BM-MSCs is
      not beneficial for facial nerve repair.

PMID- 18627309
TI  - Solution structure of Phl p 3, a major allergen from timothy grass pollen.
AB  - The major 97-aa timothy grass (Phleum pratense) allergen Phl p 3 was recently
      isolated from an extract of timothy grass pollen. Sequence comparison classifies
      this protein as a group 3 allergen. The solution structure of Phl p 3 as
      determined by nuclear magnetic resonance spectroscopy reveals that the protein
      consists of a core of hydrophobic amino-acid side chains from two beta-sheets of
      five and four anti-parallel beta-strands, respectively. This conformation is very
      similar to the crystal structure published for Phl p 2 and strongly resembles the
      known conformation of the carboxy-terminal domain of Phl p 1, the major
      difference being the loop orientations. Phl p 2 and Phl p 3 show virtually
      identical immunoreactivity, and comparison of the charged surface amino acids of
      the two proteins gives initial clues as to the IgE recognition epitopes of these
      proteins.

PMID- 18627310
TI  - Epigallocatechin gallate inhibits endothelial exocytosis.
AB  - Consumption of green tea is associated with a decrease in cardiovascular
      mortality. The beneficial health effects of green tea are attributed in part to
      polyphenols, organic compounds found in tea that lower blood pressure, reduce
      body fat, decrease LDL cholesterol, and inhibit inflammation. We hypothesized
      that epigallocatechin gallate (EGCG), the most abundant polyphenol in tea,
      inhibits endothelial exocytosis, the initial step in leukocyte trafficking and
      vascular inflammation. To test this hypothesis, we treated human umbilical-vein
      endothelial cells with EGCG and other polyphenols, and then measured endothelial
      exocytosis. We found that EGCG decreases endothelial exocytosis in a
      concentration-dependent manner, with the effects most prominent after 4 h of
      treatment. Other catechin polyphenols had no effect on endothelial cells. By
      inhibiting endothelial exocytosis, EGCG decreases leukocyte adherence to
      endothelial cells. In searching for the mechanism by which EGCG affects
      endothelial cells, we found that EGCG increases Akt phosphorylation, eNOS
      phosphorylation, and nitric oxide (NO) production. NOS inhibition revealed that
      NO mediates the anti-inflammatory effects of EGCG. Our data suggest that
      polyphenols can decrease vascular inflammation by increasing the synthesis of NO,
      which blocks endothelial exocytosis.

PMID- 18627311
TI  - Plasticity after allogeneic hematopoietic stem cell transplantation.
AB  - The postulated almost unlimited potential of transplanted hematopoietic stem
      cells (HSCs) to transdifferentiate into cell types that do not belong to the
      hematopoietic system denotes a complete paradigm shift of the hierarchical
      hemopoietic tree. In several studies during the last few years, donor cells have
      been identified in almost all recipient tissues after allogeneic HSC
      transplantation (HSCT), supporting the theory that any failing organ could be
      accessible to regenerative cell therapy. However, the putative potential ability
      of the stem cells to cross beyond lineage barriers has been questioned by other
      studies which suggest that hematopoietic cells might fuse with non-hematopoietic
      cells and mimic the appearance of transdifferentiation. Proof that HSCs have
      preserved the capacity to transdifferentiate into other cell types remains to be
      demonstrated. In this review, we focus mainly on clinical studies addressing
      plasticity in humans who underwent allogeneic HSCT. We summarize the published
      data on non-hematopoietic chimerism, donor cell contribution to tissue repair,
      the controversies related to the methods used to detect donor-derived non
      hematopoietic cells and the functional impact of this phenomenon in diverse
      specific target tissues and organs.

PMID- 18627312
TI  - Oct4 expression revisited: potential pitfalls for data misinterpretation in stem
      cell research.
AB  - The octamer-binding transcription factor 4 gene encodes a nuclear protein (Oct4,
      also known as Pou5F1 and Oct3/4) that belongs to a family of transcription
      factors containing the POU DNA-binding domain. Expression can be detected in
      embryonic stem cells as well as in adult stem cells, such as bone marrow-derived
      mesenchymal stem cells. Expression of Oct4 is downregulated coincident with stem
      cell differentiation and loss of expression leading to differentiation. A role
      for maintaining pluripotency and self-renewal of embryonic stem cells is ascribed
      to Oct4 as a pluripotency marker. Results describing Oct4 expression in
      differentiated cells, including peripheral blood mononuclear cells (PBMCs),
      neonatal and adult stem cells, as well as cancer cells, must be interpreted with
      caution. In several publications, Oct4 has been ascribed a function in
      maintaining self-renewal of adult stem cells. In contrast, other publications
      reported Oct4 expression in human tumor cells. Here, we summarize the recent
      findings on Oct4 expression and present possibilities and reasons why several
      false positive results on Oct4 expression still occur in the recent literature.
      Also, simple solutions are provided to avoid these positive signals.

PMID- 18627313
TI  - Dimerization of endogenous MT1-MMP is a regulatory step in the activation of the
      72-kDa gelatinase MMP-2 on fibroblasts and fibrosarcoma cells.
AB  - The secreted gelatinase matrix metalloprotease-2 (MMP-2) and the membrane
      anchored matrix metalloprotease MT1-MMP (MMP-14), are central players in
      pericellular proteolysis in extracellular matrix degradation. In addition to
      possessing a direct collagenolytic and gelatinolytic activity, these enzymes take
      part in a cascade pathway in which MT1-MMP activates the MMP-2 proenzyme. This
      reaction occurs in an interplay with the matrix metalloprotease inhibitor, TIMP
      2, and the proposed mechanism involves two molecules of MT1-MMP in complex with
      one TIMP-2 molecule. We provide positive evidence that proMMP-2 activation is
      governed by dimerization of MT1-MMP on the surface of fibroblasts and
      fibrosarcoma cells. Even in the absence of transfection and overexpression,
      dimerization of MT1-MMP markedly stimulated the formation of active MMP-2
      products. The effect demonstrated here was brought about by a monoclonal antibody
      that binds specifically to MT1-MMP as shown by immunofluorescence experiments.
      The antibody has no effect on the catalytic activity. The effect on proMMP-2
      activation involves MT1-MMP dimerization because it requires the divalent
      monoclonal antibody, with no effect obtained with monovalent Fab fragments. Since
      only a negligible level of proMMP-2 activation was obtained with MT1-MMP
      expressing cells in the absence of dimerization, our results identify the
      dimerization event as a critical level of proteolytic cascade regulation.

PMID- 18627314
TI  - Reconstitution of human azurocidin catalytic triad and proteolytic activity by
      site-directed mutagenesis.
AB  - Azurocidin belongs to the serprocidin family, but it is devoid of proteolytic
      activity due to a substitution of His and Ser residues in the catalytic triad.
      The aim of this study was to reconstitute the active site of azurocidin by site
      directed mutagenesis, analyze its processing and restored proteolytic activity.
      Azurocidin expressed in Sf9 insect cells possessing the reconstituted His41-Asp89
      Ser175 triad exhibited significant proteolytic activity toward casein with a pH
      optimum of approximately 8-9, but a reconstitution of only one active site amino
      acid did not result in proteolytically active protein. Enzymatically active
      recombinant azurocidin caused cleavage of the C-terminal fusion tag with the
      primary cleavage site after lysine at Lys-Leu and after alanine at Ala-Ala, and
      the secondary cleavage site after arginine at Arg-Gln, as well as with low
      efficiency caused cleavage of insulin chain B after leucine at Leu-Tyr and Leu
      Cys, and after alanine at Ala-Leu. We demonstrate that cleavage of the azurocidin
      C-terminal tripeptide is not necessary for its enzymatic activity. The first
      isoleucine present in mature azurocidin can be replaced by similar amino acids,
      such as leucine or valine, but its substitution by histidine or arginine
      decreases proteolytic activity.

PMID- 18627316
TI  - Prowling wolves in sheep's clothing: the search for tumor stem cells.
AB  - The importance of a subset of cells which have 'stem like' characteristics and
      are capable of tumor initiation has been reported for a range of tumors.
      Isolation of these tumor-initiating cells (TICs) has largely been based on
      differential cell surface protein expression. However, there is still much debate
      on the functional significance of these markers in initiating tumors, as many
      properties of tumor initiation are modified by cell-cell interactions. In
      particular, the relationship between TICs and their microenvironment is poorly
      understood but has therapeutic implications, as the microenvironment can maintain
      tumor cells in a prolonged period of quiescence. However, a major limitation in
      advancing our understanding of the crosstalk between TICs and their
      microenvironment is the lack of sensitive techniques which allow the in vivo
      tracking and monitoring of TICs. Application of new in vivo cellular and
      molecular imaging technologies holds much promise in uncovering the mysteries of
      TIC behavior at the three-dimensional level. This review will describe recent
      advances in our understanding of the TIC concept and how the application of in
      vivo imaging techniques can advance our understanding of the biological fate of
      TICs. A supplementary resource guide describing TICs from different malignancies
      is also presented.

PMID- 18627315
TI  - Elimination of hop latent viroid upon developmental activation of pollen
      nucleases.
AB  - Hop latent viroid (HLVd) is not transmissible through hop generative tissues and
      seeds. Here we describe the process of HLVd elimination during development of hop
      pollen. HLVd propagates in uninucleate hop pollen, but is eliminated at stages
      following first pollen mitosis during pollen vacuolization and maturation. Only
      traces of HLVd were detected by RT-PCR in mature pollen after anthesis and no
      viroid was detectable in in vitro germinating pollen, suggesting complete
      degradation of circular and linear HLVd forms. The majority of the degraded HLVd
      RNA in immature pollen included discrete products in the range of 230-100
      nucleotides and therefore did not correspond to siRNAs. HLVd eradication from
      pollen correlated with developmental expression of a pollen nuclease and specific
      RNAses. Activity of the pollen nuclease HBN1 was maximal during the vacuolization
      step and decreased in mature pollen. Total RNAse activity increased continuously
      up to the final steps of pollen maturation. HBN1 mRNA, which is abundant at the
      uninucleate microspore stage, encodes a protein of 300 amino acids (34.1 kDa,
      isoeletric point 5.1). Sequence comparisons revealed that HBN1 is a homolog of S1
      like bifunctional plant endonucleases. The developmentally activated HBN1 and
      pollen ribonucleases could participate in the mechanism of HLVd recognition and
      degradation.

PMID- 18627318
TI  - Lineage development of hematopoietic stem and progenitor cells.
AB  - Hematopoietic stem cells have the potential to develop into multipotent and
      different lineage-restricted progenitor cells that subsequently generate all
      mature blood cell types. The classical model of hematopoietic lineage commitment
      proposes a first restriction point at which all multipotent hematopoietic
      progenitor cells become committed either to the lymphoid or to the myeloid
      development, respectively. Recently, this model has been challenged by the
      identification of murine as well as human hematopoietic progenitor cells with
      lymphoid differentiation capabilities that give rise to a restricted subset of
      the myeloid lineages. As the classical model does not include cells with such
      capacities, these findings suggest the existence of alternative developmental
      pathways that demand the existence of additional branches in the classical
      hematopoietic tree. Together with some phenotypic criteria that characterize
      different subsets of multipotent and lineage-restricted progenitor cells, we
      summarize these recent findings here.

PMID- 18627317
TI  - A hypoallergenic hybrid molecule with increased immunogenicity consisting of
      derivatives of the major grass pollen allergens, Phl p 2 and Phl p 6.
AB  - Allergen-specific immunotherapy is currently based on the administration of
      allergen extracts containing natural allergens. However, its broad application is
      limited by the poor quality of these extracts. Based on recombinant allergens,
      well-defined allergy vaccines for allergen-specific immunotherapy can be
      produced. Furthermore, they can be modified to reduce their allergenic activity
      and to avoid IgE-mediated side effects. Here, we demonstrate that the
      immunogenicity of two grass pollen-derived hypoallergenic allergen derivatives
      could be increased by engineering them as a single hybrid molecule. We used a
      hypoallergenic Phl p 2 mosaic, generated by fragmentation of the Phl p 2 sequence
      and reassembly of the resulting peptides in an altered order, and a truncated Phl
      p 6 allergen, to produce a hybrid protein. The hybrid retained the reduction of
      IgE reactivity and allergenic activity of its components as shown by ELISA and
      basophil activation assays. Immunization with the hybrid molecule demonstrated
      the increased immunogenicity of this molecule, leading to higher levels of
      allergen-specific IgG antibodies compared to the single components. These
      antibodies could inhibit patients' IgE binding to the wild-type allergens. Thus,
      the described strategy allows the development of safer and more efficacious
      vaccines for the treatment of grass pollen allergy.

PMID- 18627319
TI  - Prospective of Ras signaling in stem cells.
AB  - The Ras signaling pathway plays a predominant role during development and
      controls diverse biological process in all eukaryotic cells. It is a member of
      the large family of GTPases proteins that binds and hydrolyzes GTP. Ras is a
      lipid-anchored protein on the intracellular membrane compartments, and cycles
      between inactive GDP-bound and the signaling competent GTP-bound conformation.
      Studies have demonstrated Ras to be a central regulator in signal transduction
      pathways responding to diverse extracellular and intracellular stimuli. Much
      progress has been made towards delineating specific genes involved in the process
      of pluripotency and differentiation of stem cells. Here, we discuss recent
      aspects of Ras signaling pathways in mediating stem cell properties.

PMID- 18627320
TI  - Cytokine combinations differentially influence the SDF-1alpha-dependent migratory
      activity of cultivated murine hematopoietic stem and progenitor cells.
AB  - Stromal cell-derived factor-1alpha (SDF-1alpha) is a strong migratory stimulant
      for hematopoietic stem and progenitor cells (HSPCs). The hematopoietic cytokines
      thrombopoietin (TPO), Flt3-ligand (FL), stem cell factor (SCF) and interleukin 11
      (IL-11) are able to stimulate amplification of primitive murine hematopoietic
      stem cells (HSCs) in vitro. The effects of these cytokines on SDF-1alpha-induced
      migratory activity of murine Lin(-)c-kit+ HSPC were analyzed by cultivation of
      these cells in the presence of 12 combinations of FL, TPO, SCF and IL-11.
      Migratory activity was measured in a three-dimensional collagen matrix using time
      lapse video microscopy. Each cytokine combination had a distinct effect on SDF
      1alpha-stimulated migratory activity. For instance, FL- and SCF-cultivated cells
      showed a high migratory SDF-1alpha response, while cells cultivated with SCF, TPO
      and IL-11 did not react to SDF-1alpha stimulation with an elevated migration
      rate. Our data indicate that the differences in the migratory SDF-1alpha response
      are not related to different CXCR4 expression levels, but rather to the
      differential engagement of the CXCR4-dependent MAPK p42/44 and PI3K signal
      transduction pathways. This indicates that hematopoietic cytokines can have a
      significant impact on SDF-1alpha-stimulated migratory activity and the underlying
      intracellular signaling processes in cultivated HSPCs.

PMID- 18627321
TI  - Effects of extended-release tramadol on pain-related sleep parameters in patients
      with osteoarthritis.
AB  - OBJECTIVE: To examine the effects of extended release tramadol (tramadol ER) on
      reducing pain-related sleep disturbances (PRSDs) in patients (20-80 years) with
      moderate to moderately severe pain with radiographically confirmed osteoarthritis
      (OA) of the knee or hip. METHODS: A post hoc analysis of two 12-week, double
      blind, placebo-controlled, randomized, parallel-group studies was conducted. In
      Study A, patients (n = 1,020) received tramadol ER 100, 200, 300, or 400 mg, or
      placebo. In Study B (n = 1,011), patients received tramadol ER 100, 200, or 300
      mg, or placebo. MAIN OUTCOME MEASURES: PRSDs were evaluated using the Chronic
      Pain Sleep Inventory (CPSI) based on a 100-mm visual analog scale (VAS; 0 = very
      poor, 100 = excellent for the overall quality of sleep). RESULTS: Significant
      improvements in CPSI scores from baseline were seen as early as week 1 in all
      tramadol ER groups and were maintained through the final visit for overall sleep
      quality compared with placebo (all p < or = 0.022). Compared with placebo,
      significant improvements in scores from baseline were seen beginning at week 1
      for tramadol ER 200 and 300 mg and week 3 for tramadol ER 100 mg, and were
      maintained in all dose groups through the final visit, for being awakened by pain
      in the night and in the morning, and less trouble falling asleep due to pain (all
      p < or = 0.046). CONCLUSION: In this post hoc analysis, a reduction in pain was
      associated with a significant reduction in PRSDs due to OA.

PMID- 18627322
TI  - Effects of ezetimibe, either alone or in combination with atorvastatin, on serum
      visfatin levels: a pilot study.
AB  - INTRODUCTION: Ezetimibe inhibits intestinal absorption of cholesterol and lowers
      circulating low-density lipoprotein cholesterol levels. Visfatin is a novel
      adipokine, which may be implicated in the atherosclerotic process. OBJECTIVE: The
      aim of this study was to explore the possible association between ezetimibe
      administration and serum visfatin concentrations. METHODS: Patients (n = 30) with
      primary dyslipidemia and another 30 who failed to reach their assigned low
      density lipoprotein cholesterol target on atorvastatin therapy (20 mg/day) were
      included in the study. All participants were given ezetimibe at 10 mg/day for 12
      weeks. RESULTS: At baseline the visfatin levels correlated significantly with the
      total cholesterol (r = 0.61 and p < 0.01) and low-density lipoprotein cholesterol
      (r = 0.51 and p < 0.01) levels in the statin pretreatment group. Furthermore, in
      the statin group the post-treatment levels of visfatin and low-density
      lipoprotein cholesterol were significantly correlated (r = 0.57 and p < 0.01).
      The serum visfatin concentrations did not change significantly in either the
      monotherapy or statin pretreatment groups or in subgroups divided according to
      the baseline lipid variables. In both the ezetimibe monotherapy and ezetimibe
      plus atorvastatin groups the effect of ezetimibe on the lipid variables depended
      on the baseline lipid values. The low-density lipoprotein cholesterol:high
      density lipoprotein cholesterol ratio was consistently improved by ezetimibe in
      all groups or subgroups. CONCLUSIONS: Ezetimibe did not alter serum visfatin
      concentrations, either when administered as monotherapy or combined with a
      statin. Future studies investigating the effect of ezetimibe on visfatin levels
      need to include groups of patients with distinct lipid characteristics.

PMID- 18627323
TI  - Effect of two low-dose gestodene containing monophasic oral contraceptives on
      hemostasis in Bulgarian women.
AB  - OBJECTIVE: To compare the effects of two monophasic oral contraceptives upon
      coagulation, fibrinolysis and the system of natural inhibitors (anticoagulant
      pathways) in Bulgarian women. METHODS: This prospective, open clinical study
      lasted 12 months and included 70 women, divided into two equal groups of 35 each.
      The women from group A received a contraceptive containing 20 microg
      ethinylestradiol/75 microg gestodene. The women from group B received a
      contraceptive containing 30 microg ethinylestradio l/75 microg gestodene. At the
      beginning and again at the end of the study, the following values were
      determined: prothrombin time (PT), activated partial thromboplastic time (aPTT),
      thrombin time (TT), fibrinogen (F), Factor VII (FVII), Factor X (FX),
      plasminogen, alpha 2-antiplasmin, tissue-type plasminogen activator (t-PA), D
      dimers, protein C (Pr C), total Protein S (TPr S), antithrombin III (AT III) and
      heparin Cofactor II (HC II). RESULTS: We did not find any statistically
      significant differences in the global tests of hemostasis (PT, aPTT, TT) in
      either group compared with the baseline values. At the end of the study there was
      an increase in the levels of fibrinogen, FX, PrC and H II, and also diminution of
      t-PA in both groups in comparison with the baseline values. At the end of the
      study the activity of FVII, alpha2-antiplasmin and AT III was elevated only in
      group B. Although certain alterations in hemostasis parameters were observed, all
      of them were within the reference range. We did not observe or suspect any cases
      of vascular, thrombotic or other incidence in the observed groups of 840 cycles
      of hormonal contraception over the 12-month period. CONCLUSION: There is an
      increase in both procoagulant and fibrinolytic activity when using low-dose
      gestodene containing monophasic oral contraceptives. This can be interpreted as a
      shift to a higher equilibrium. There is no need for screening for thrombofilia in
      healthy, non-obese, non-smoking Bulgarian females, aged between 18 to 35 years,
      without a personal or family history of thrombotic diseases, before starting on
      third generation oral contraceptive with gestodene.

PMID- 18627324
TI  - A strategy for developing effective amyotropic lateral sclerosis pharmacotherapy:
      from clinical trials to novel pharmacotherapeutic strategies.
AB  - BACKGROUND: The pathomechanism of sporadic amyotropic lateral sclerosis is not
      clearly understood, although a proportion of familial amyotropic lateral
      sclerosis is caused by superoxide dismutase 1 mutations. Theories based on
      studies of human post-mortem tissue, research on animal models and in vitro work
      have been proposed for the pathogenesis of amyotropic lateral sclerosis, but the
      pathogenesis is not the same between sporadic and familial amyotropic lateral
      sclerosis. OBJECTIVE/METHODS: Drug candidates were tested using superoxide
      dismutase 1 mutant mice. Although the candidates were shown to be effective in
      mice, clinical trials in humans have failed to identify any truly effective
      pharmacotherapies in sporadic amyotropic lateral sclerosis, with only riluzole
      providing a modest improvement in survival. Ongoing or planned trials are
      exploring the value of antiglutamatergic drugs, antioxidants, neurotrophic
      factors, anti-inflammatory drugs and anti-aggregation drugs. RESULTS/CONCLUSIONS:
      A combination of drugs acting on different mechanisms is needed for effective
      therapy. Moreover, gene expression profiling and genome-wide association studies,
      together with inhibitory RNA techniques, are helpful for developing new
      pharmacotherapeutic strategies including gene therapy. It is also likely that the
      recently advanced generation of induced pluripotent stem cells will lead to the
      development of cell therapy for amyotropic lateral sclerosis. In addition to
      finding effective therapies, research is also needed in order to detect early
      disease markers since pharmacotherapy is most beneficial when given early in the
      course of sporadic amyotropic lateral sclerosis.

PMID- 18627325
TI  - Treatment options for pregnant women with epilepsy.
AB  - BACKGROUND: Antiepileptic drugs (AEDs) in pregnancy are associated with an
      increased risk of fetal malformations. Concern is expressed about the effects
      that AEDs may produce on the child's cognition and development. To date, no
      specific malformations have clearly been proven to be attributable to a specific
      drug, with the exception of valproate. OBJECTIVE: In order to gain prospective
      data, collaborative pregnancy registers have been established which collect data
      on teratogenicity and seizure control efficacy of AEDs, and on the comparative
      efficacy of second-generation AEDs. METHODS: Studies of the effects of AED
      exposure on cognitive function have begun. Future head-to-head studies of
      traditional and newly developed AEDs may provide a more rational basis for
      defining first and second line choices of medications for women with epilepsy
      generally, and more specifically in pregnancy. CONCLUSIONS: Traditional
      prescribing patterns appear to influence the options for treatment of women with
      epilepsy in pregnancy, which is then adjusted according to the variability of
      response.

PMID- 18627326
TI  - Major bleeding: management and risk reduction in acute coronary syndromes.
AB  - BACKGROUND: Guidelines for the management of high-risk non ST-segment elevation
      acute coronary syndrome (NSTE ACS) recommend antithrombotic and antiplatelet
      therapy combined with an early invasive strategy. While this strategy reduces
      ischemic complications, it places patients at risk for bleeding complications.
      OBJECTIVE: We sought to provide a narrative review of the risk factors for
      bleeding, risks associated with bleeding and strategies to prevent bleeding
      complications. METHODS: A comprehensive literature review was performed to
      identify relevant evidence. RESULTS/CONCLUSIONS: Bleeding complications in NSTE
      ACS are associated with adverse events and higher mortality. Prevention of
      bleeding complications can be achieved through judicious dosing of medications,
      the use of antithrombotic agents associated with a lower bleeding risk and use of
      the radial artery approach in patients requiring coronary intervention. Future
      work should focus on delineating the mechanisms underlying the bleeding-mortality
      relationship and developing a better understanding of the tradeoff between
      efficacy and safety.

PMID- 18627327
TI  - Neoadjuvant chemotherapy preceding cystectomy for bladder cancer.
AB  - BACKGROUND: Occult micrometastasis at the time of radical cystectomy leads
      predominantly to distant failures in patients with locally advanced, muscle
      invasive transitional cell carcinoma of the bladder. OBJECTIVES: Data supporting
      neoadjuvant chemotherapy for locally advanced bladder cancer are reviewed.
      RESULTS: Studies evaluating adjuvant chemotherapy have been limited by inadequate
      statistical power. However, randomized clinical trials have demonstrated a
      survival benefit for neoadjvuant cisplatin-based combination chemotherapy. Trials
      employing neoadjuvant therapy are particularly valuable in the development of
      novel systemic therapy regimens, since pathological complete remission appears to
      be a powerful prognostic factor for long-term survival. CONCLUSION: Neoadjuvant
      chemotherapy is a standard for the therapy of locally advanced bladder cancer,
      and the neoadjuvant paradigm may assist in accelerating novel agent development.

PMID- 18627328
TI  - Burns: what are the pharmacological treatment options?
AB  - BACKGROUND: Many advances have been made in the understanding and management of
      burn injury, dramatically increasing pharmacological decision options for burn
      care professionals. Since burn injury is so multi-faceted, these advances cross
      many injury processes, both acute and chronic. OBJECTIVE: The purpose of this
      review was to highlight the advances and decision options across the entire scope
      of the burn injury process. The burn-related processes with the most significant
      pharmacological options of approved products are highlighted. METHODS: The scope
      of the current research is the most pertinent literature, which has been
      summarized with the addition of a personal perspective. RESULTS/CONCLUSIONS: Many
      advances over the past decade in multiple fields have made pharmacological
      options plentiful in burn care. That said, there are many problems for the burn
      patient which persist, making burn injury still the most severe form of trauma.
      These issues range from management of a catabolic state with involuntary weight
      loss in the critical burn to severe itching in the rehabilitating patient. There
      are also many more treatment options available today. Two key reasons stand out
      as the most prominent. One reason is the fact that burn care has become much more
      proactive, by searching out new approaches to solve old problems. Now the
      treatment approach is altering its focus on manipulating the course of a burn.
      Examples include the use of temporary skin substitutes in partial thickness or
      second degree burns, decreasing pain and increasing the healing rate. Another is
      the use of slow release silver dressing as the topical burn wound antimicrobial
      of choice, markedly reducing discomfort, the need for dressing changes and an
      overall decrease in infection. In larger, deeper burns, the approach has changed
      from the chronic management of an open burn wound to rapid excision and wound
      closure, eliminating the burn as a source of complications. In addition, there
      has been a very aggressive approach to controlling the profound hypermetabolic,
      catabolic response to burns, rather than simply treating the outcome of this
      predictable post-burn complication. Approaching psychosocial stress again by
      prevention rather than treatment of established problems is another example. The
      second reason for increased options and differences in management involves the
      mindset of those individuals taking care of burns. Tremendous differences in
      experience are involved in decision-making. Different opinions are based on the
      expertise and also the personal preferences of those managing the burn.

PMID- 18627329
TI  - Pharmacotherapy in patients with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Based on the recognition of idiopathic pulmonary fibrosis as a
      fibroproliferative disease with the usual interstitial pneumonia histology,
      pharmacotherapies should be reconsidered. OBJECTIVE: The aim of this study was to
      grasp the therapeutic efficacy of the drugs for idiopathic pulmonary fibrosis
      patients based on reports and the authors' own experiences. METHODS: The study
      reviewed a spectrum of therapeutic strategies and the current problems in the
      drug treatments for idiopathic pulmonary fibrosis/usual interstitial pneumonia
      patients based on reported references. RESULTS/CONCLUSIONS: Unfortunately, the
      presence of usual interstitial pneumonia lesions increases the likelihood that
      idiopathic pulmonary fibrosis will resist various types of drug therapies. The
      most practical and critical points of therapeutic view are the following. First,
      for advanced idiopathic pulmonary fibrosis patients, small maintenance doses of
      drugs could reduce several adverse effects. Second, there needs to be early
      detection of pulmonary hypertension, which is an unfavorable prognostic factor
      and trial of vasodilators in patients with pulmonary hypertension. Third, for
      early stable patients, a large randomized controlled trial (using antifibrotic
      and immunomodulatory drugs) should be undertaken in order to obtain feasible
      results.

PMID- 18627330
TI  - Novelties in the multifaceted miconazole effects on skin disorders.
AB  - BACKGROUND: Miconazole nitrate is a time-honored antifungal of the imidazole
      class. OBJECTIVE: To revisit the various aspects of action of the drug in a
      dermatologic setting. METHOD: Review of the current peer-reviewed publications.
      RESULTS/CONCLUSION: Miconazole essentially inhibits 14alpha-demethylase, an
      enzyme required for the biosynthesis of ergosterol, which is the main sterol
      constituent of fungal cell membranes. Hence, toxic methylated sterols accumulate.
      Synthesis of triglycerides and phospholipids is also affected. In addition,
      miconazole also exhibits other ancillary mechanisms of action that probably
      participate in the therapeutic efficacy of the drug. The oxidative and
      peroxidative enzyme activities are altered leading to an intracellular build up
      of a toxic concentration of hydrogen peroxide. This may contribute to the
      deterioration of subcellular organelles and to cell necrosis. Farnesol synthesis
      is stimulated in Candida spp. leading to the prevention of yeast-to-mycelium
      formation. Overall, miconazole is fungistatic through its effect on ergosterol
      biosynthesis, but it may also have a fungicidal effect against a number of fungal
      species due to its effect on hydrogen peroxide accumulation. In addition,
      miconazole is active against a series of Gram-positive bacteria and has been
      shown to help the repair of the skin barrier function and to help mitigate some
      inflammatory cell reactions (such as in acne). To conclude, miconazole exerts
      multi-pronged effects both against pathogenic fungi and on skin physiology.

PMID- 18627331
TI  - Nitric oxide: new evidence for novel therapeutic indications.
AB  - BACKGROUND: Nitric oxide (NO) deficiency is implicated in many pathophysiological
      processes in mammals. NO is a ubiquitous molecule involved in multiple cellular
      functions. Uncontrolled or inappropriate production of NO may lead to several
      disease states including septic shock, rheumatoid and inflammatory arthropathies,
      and expansion of cerebral damage after stroke. However, to date, there are no
      therapeutic agents available that can overcome these conditions. Similarly,
      underproduction of NO by NO synthase or enhanced breakdown of NO also leads to
      diseases such as hypertension, ischemic conditions, pre-eclampsia, premature
      delivery, among others. NO donor therapies are indicated in these conditions.
      RESULTS: Nitroglycerin and nitrates (NO donors) have been used as therapeutic
      agents for the past century, particularly to treat vascular disease, and the only
      significant adverse effects are headaches. NO donors are highly cost-effective
      and have beneficial effects in multiple body systems. When the body cannot
      generate NO via NO synthase or due to rapid turnover leading to inadequate
      amounts of NO available for biological homeostasis, administration of exogenous
      NO, or prolongation of the actions of endogenous NO, are practical ways to
      supplement NO. CONCLUSION: Recipients of such therapy include patients with
      angina pectoris, coronary artery disease, hypertension, osteoporosis,
      gastrointestinal motility disorders, pregnancy-related disorders including
      premature delivery, pre-eclampsia, vulvodynia, and erectile dysfunction in men.
      Postmenopausal NO deficiency is rectified with hormone replacement therapy, which
      enhances local production of NO. Declining local NO production secondary to
      estrogen deficiency in postmenopausal women and perhaps in older men could be one
      of the reasons for age-related increased incidences of cardiovascular events and
      sexual dysfunction. Thus, in addition to supplementation of NO compounds in acute
      situations like alleviating angina and erectile dysfunction, chronic NO therapy
      is cost-effective in decreasing cardiovascular events, and improving the
      urogenital system and skeletal health.

PMID- 18627332
TI  - Morphine-6-glucuronide: potency and safety compared with morphine.
AB  - BACKGROUND: In contemporary medicine, morphine remains the drug of choice in the
      treatment of severe postoperative pain. Nevertheless, morphine has several side
      effects, which can seriously compromise its analgesic effectiveness and the
      patient safety/compliance. The search for opioid analgesics with a better side
      effect profile than morphine has led to a morphine metabolites, morphine-6
      glucuronide (M6G). OBJECTIVE: The objectives of the current paper are to give an
      overview of the analgesic properties of M6G, assess the dose range at which it
      produces equianalgesia to morphine and explore its side-effect profile. METHODS:
      A review of published clinical studies (Phase II - III) on M6G in the treatment
      of experimental and clinical pain is given. RESULTS/CONCLUSIONS: M6G > 0.2 mg/kg
      is an effective analgesic with a slower onset but longer duration of action (> 12
      h) compared with morphine. Side effects, most importantly postoperative nausea
      and vomiting, occur less frequent after M6G treatment. M6G is an attractive
      alternative to morphine in the treatment of severe postoperative pain.

PMID- 18627333
TI  - Argatroban use in heparin-induced thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious, life-threatening
      complication which occurs in 1-3% of patients receiving heparin. Patients with
      untreated HIT have an up to 50% risk of developing life- and limb-threatening
      thromboembolic complications. Treatment is based upon clinical suspicion,
      stopping heparin therapy and initiation of anticoagulation with a rapidly acting
      alternative non-heparin anticoagulant, such as argatroban-a hepatically excreted
      direct thrombin inhibitor which is effective in the treatment of HIT. OBJECTIVE:
      To summarize the pharmacological and clinical data, and discuss the impact of
      argatroban in the current treatment of HIT. METHODS: A literature search was
      performed with the aid of Pubmed and Google. Search parameters of 'argatroban',
      'heparin-induced thrombocytopenia' and 'treatment' were input into both search
      engines. CONCLUSION: Argatroban is a safe and effective treatment for HIT. In
      patients taking other hepatically cleared medications, lower initial doses may
      have to be used to avoid over-anticoagulation.

PMID- 18627334
TI  - Docetaxel in the management of prostate cancer: current standard of care and
      future directions.
AB  - BACKGROUND: Advanced and metastatic prostate cancer continues to represent a
      significant healthcare burden. Since the publication of two randomized trials
      that showed significant survival and palliative benefits for men treated with
      docetaxel, this drug has become the treatment of choice for patients with
      metastatic castration resistant prostate cancer (CRPC). OBJECTIVE: This review
      discusses the development and current use of docetaxel in metastatic CRPC, as
      well as future clinical applications. METHODS: The current literature, meeting
      abstracts and ClinicalTrials.gov have been reviewed. The most relevant studies
      involving patients with prostate cancer receiving therapy with docetaxel, alone
      or in combination with other agents, have been summarised. CONCLUSION: Docetaxel
      monotherapy is the approved treatment for patients with metastatic CRPC, and its
      association with other agents, such as targeted therapies, is currently under
      study. Several trials are currently ongoing to investigate the use of docetaxel
      in the early stages of disease, particularly in the neoadjuvant and adjuvant
      settings for patients with high-risk disease.

PMID- 18627335
TI  - Azacitidine and the beginnings of therapeutic epigenetic modulation.
AB  - BACKGROUND: Although originally developed as a cytarabine analog more than 40
      years ago, azacitidine has been the subject of renewed interest in the era of
      cancer epigenetics. OBJECTIVE: What is the history of the clinical development of
      azacitidine and how has it been applied successfully to the treatment of
      myelodysplastic syndromes (MDS)? METHODS: We review the evolution of the use of
      azacitidine for the therapy of human disease and review the major studies that
      have laid the groundwork for its current clinical indication. CONCLUSION: The use
      of azacitidine has changed the approach to the treatment of MDS and has resulted
      in improved outcomes for patients.

PMID- 18627336
TI  - Imiglucerase and its use for the treatment of Gaucher's disease.
AB  - BACKGROUND: Gaucher's disease is caused by deficient lysosomal glucocerebrosidase
      activity. Intravenous enzyme replacement therapy with imiglucerase (Cerezyme,
      Genzyme Corporation, Cambridge, MA), a recombinant human glucocerebrosidase,
      ameliorates systemic manifestations such as hepatosplenomegaly, anemia,
      thrombocytopenia and skeletal abnormalities in patients with type 1 (non
      neuronopathic) and type 3 (chronic neuronopathic) Gaucher's disease.
      OBJECTIVE/METHODS: The aim of this study was to identify and comment on the
      current issues related to imiglucerase for Gaucher's disease based on a review of
      published English language literature and personal clinical experience. RESULTS:
      The following topics were covered with respect to imiglucerase: development,
      pharmacokinetics, preparation and administration, efficacy, pediatrics,
      pregnancy, type 3 Gaucher's disease, dosing, treatment interruptions, safety and
      alternative pharmacological therapies. CONCLUSION: Imiglucerase is safe and well
      tolerated. In addition, it corrects the hepatic, splenic, hematologic and bone
      abnormalities observed with types 1 and 3 Gaucher's disease effectively and
      enhances health-related quality of life.

PMID- 18627337
TI  - Clobetasol propionate emollient formulation foam in the treatment of
      corticosteroid-responsive dermatoses.
AB  - BACKGROUND: Topical corticosteroids are the most common treatment modality for
      patients with psoriasis and atopic dermatitis; however, the efficacy of topical
      corticosteroids is often hampered by barriers to patient adherence, such as lack
      of efficacy, side effects and inconvenience. Recently published studies have
      investigated the safety and efficacy of a novel emollient foam (EF) formulation
      of clobetasol propionate (CP), a class I topical corticosteroid in psoriasis and
      atopic dermatitis. OBJECTIVES: To summarize recent literature on CP EF foam, and
      to evaluate recent Phase II and III clinical trials of CP EF foam in psoriasis
      and atopic dermatitis. METHODS: The MEDLINE (1950 - January 2008) database was
      searched using the following terms: 'clobetasol propionate foam', 'topical
      corticosteroids', 'topical glucocorticoids', 'psoriasis' and 'atopic dermatitis'.
      Results were evaluated for relevance and quality, and additional references were
      obtained from bibliographies of selected articles. CONCLUSION: CP EF foam appears
      to be safe and effective for corticosteroid-responsive dermatoses in adults and
      children > or = 12 years of age. As compared to its hydroethanolic foam
      predecessor, CP EF presents a potential advance for patients who are less likely
      to tolerate alcohol-based foam. As alcohol-based foams can be irritating and
      cause stinging in non-hair-bearing areas, this new emollient formulation has the
      potential to widen the use of CP foam to more patients with atopic dermatitis and
      to more non-scalp body sites in patients with psoriasis.

PMID- 18627338
TI  - Is tocilizumab an option for the treatment of arthritis?
AB  - BACKGROUND: Some patients with rheumatoid arthritis and systemic-onset juvenile
      idiopathic arthritis are resistant to inhibitors of interleukin-1 and tumour
      necrosis factor. Raised levels of interleukin-6 are associated with both these
      conditions. Tocilizumab is a humanised monoclonal antibody that binds to both
      forms of interleukin-6 receptor that has recently been used in Phase III trials
      in rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis.
      METHODS: The study conducted an evaluation of Phase III trials with tocilizumab.
      RESULTS: In the Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders
      the primary efficacy end-point was the proportion of subjects with a 20%
      improvement in their rheumatoid arthritis signs and symptoms according to the
      American College of Rheumatology criteria and, at 24 weeks, this value was 26%
      with placebo and was increased to 48 and 59% with tocilizumab at 4 and 8 mg
      respectively. In the trial of tocilizumab in systemic-onset juvenile idiopathic
      arthritis, the primary end-point in the open-label lead-in was the proportion of
      subjects achieving an American College of Rheumatology Pediatric 30 response and
      91% of subjects had achieved this at 6 weeks. This response was maintained by the
      majority of subjects being treated with tocilizumab during a 12-week double-blind
      trial and 48 weeks of open trial follow-up. Small numbers of subjects developed
      infections in both studies. CONCLUSIONS: Provided long-term safety can be
      established, tocilizumab will probably become part of the treatment for
      rheumatoid arthritis and may become a major breakthrough for the treatment of
      systemic-onset juvenile idiopathic arthritis.

PMID- 18627339
TI  - Intravitreal bevacizumab treatment for refractory diabetic macular edema.
AB  - AIMS: The aim of this study was to report the short-term clinical and
      angiographic outcomes after an intravitreal injection of bevacizumab in eyes with
      refractory diabetic macular edema. METHODS: Patients who had been treated with
      both grid-laser photocoagulation and intravitreal trimacinolone acetonide
      injections for diabetic macular edema received intravitreal bevacizumab (0.125
      mg/0.05 mL). Snellen visual acuity testing and fluorescien angiography were
      performed before and 1 month after the injection for each patient. RESULTS:
      Seventeen (17) eyes of 16 patients were included in the study. All patients
      completed 6 weeks of follow-up. Visual acuity improved in 12 eyes (70%) and
      remained the same in 5 eyes (30%). Eight (8) eyes (47%) revealed a marked
      improvement of macular edema, 6 eyes (35%) revealed mild improvement, and 3 eyes
      (18%) had no change. None of the patients developed local or systemic adverse
      events. CONCLUSIONS: Intravitreal injection of bevacizumab may be effective in
      the treatment of refractory diabetic edema unresponsive to laser photocoagulation
      and an intravitreal triamcinolone injection.

PMID- 18627341
TI  - Kallikreins and kallikrein-related peptidases.

PMID- 18627340
TI  - A comparison of dorzolamide/timolol-fixed combination versus bimatoprost in
      patients with open-angle glaucoma who are poorly controlled on latanoprost.
AB  - PURPOSE: The aim of this study was to evaluate the intraocular pressure (IOP)
      efficacy and safety of dorzolamide/timolol in fixed combination (DTFC) versus
      bimatoprost in open-angle glaucoma (OAG) patients poorly controlled (> or =21
      mmHg) on latanoprost. METHODS: This was a prospective, double-masked, randomized,
      controlled, cross-over evaluation. After a 6-week wash-out period, the patients
      then returned for baseline diurnal curve testing every 2 h (8 AM to 8 PM).
      Patients with an IOP of 22-29 mmHg inclusive at 8 AMwere randomized to either
      bimatoprost dosed each evening or DTFC twice-daily. Patients returned in 8 weeks
      for the Period 1 diurnal curve and were switched to the opposite treatment.
      Patients again returned in 8 weeks for the Period 2 diurnal curve. RESULTS: Of
      the 29 patients, mean untreated baseline IOP (visit 2) was 24.6 +/- 2.6 mmHg and
      treatment mean IOP was statistically lower with bimatoprost 17.6 +/- 2.0 mmHg
      than for DTFC 18.8 +/- 2.5 mmHg (P = 0.03), as was the IOP range (P = 0.02) and
      IOP peak (P = 0.003). No significant differences were found between DTFC and
      bimatoprost at individual time points after a modified Bonferroni correction
      (>0.02). DTFC demonstrated a greater incidence of stinging or burning (n = 12)
      than bimatoprost (n = 0; P = < 0.0001). CONCLUSIONS: This study suggests that OAG
      patients generally can obtain similar IOP control at individual time points (when
      a Bonferroni correction is considered) by switching to either DTFC or
      bimatoprost, but overall diurnal control is statistically better with
      bimatoprost.

PMID- 18627342
TI  - The 2nd International Symposium on Kallikreins and Kallikrein-Related Peptidases
      (ISK 2007) and the Commemorative Gold Medal of the E.K. Frey-E. Werle Foundation
      of the Henning L. Voigt Family.

PMID- 18627343
TI  - Structures and specificity of the human kallikrein-related peptidases KLK 4, 5,
      6, and 7.
AB  - Human kallikrein-related peptidases (KLKs) are (chymo)-trypsin-like serine
      proteinases that are expressed in a variety of tissues such as prostate, ovary,
      breast, testis, brain, and skin. Although their physiological functions have been
      only partly elucidated, many of the KLKs appear to be useful prognostic cancer
      markers, showing distinct correlations between their expression levels and
      different stages of cancer. Recent advances in the purification of 'new type'
      recombinant KLKs allowed solution of the crystal structures of KLK4, KLK5, KLK6,
      and KLK7. Along with these data, enzyme kinetic studies and extended substrate
      specificity profiling have led to an understanding of the non-prime-side
      substrate preferences of KLK4, 5, 6, and 7. The shape and polarity of the
      specificity pockets S1-S4 explain well their substrate preferences. KLK4, 5, and
      6 exhibit trypsin-like specificity, with a strong preference for Arg at the P1
      position of substrates. In contrast, KLK7 displays a unique chymotrypsin-like
      specificity for Tyr, which is also preferred at P2. All four KLKs show little
      specificity for P3 residues and have a tendency to accept hydrophobic residues at
      P4. Interestingly, for KLK4, 5, and 7 extended charged surface regions were
      observed that most likely serve as exosites for physiological substrates.

PMID- 18627344
TI  - Development of peptides specifically modulating the activity of KLK2 and KLK3.
AB  - The prostate produces several proteases, the most abundant ones being kallikrein
      related peptidase 3 (KLK3, PSA) and KLK2 (hK2), which are potential targets for
      tumor imaging and treatment. KLK3 expression is lower in malignant than in normal
      prostatic epithelium and it is further reduced in poorly differentiated tumors,
      in which the expression of KLK2 is increased. KLK3 has been shown to inhibit
      angiogenesis, whereas KLK2 may mediate tumor growth and invasion by participating
      in proteolytic cascades. Thus, it may be possible to control prostate cancer
      growth by modulating the proteolytic activity of KLK3 and KLK2. We have developed
      peptides that very specifically stimulate the activity of KLK3 or inhibit that of
      KLK2. Using these peptides we have established peptide-based methods for the
      determination of enzymatically active KLK3. The first-generation peptides are
      unstable in vivo and are rapidly cleared from the circulation. Currently we are
      modifying the peptides to make them suitable for in vivo applications. We have
      been able to considerably improve the stability of KLK2-binding peptides by
      cyclization. In this review we summarize the possible roles of KLK3 and KLK2 in
      prostate cancer and then concentrate on the development of peptides that modulate
      the activity of these proteases.

PMID- 18627347
TI  - Regulation of reactive oxygen species and genomic stability in hematopoietic stem
      cells.
AB  - Hematopoietic stem cells (HSCs) are defined by their ability both to self-renew
      and to give rise to fresh blood cells throughout the lifetime of an animal. The
      failure of HSCs to self-renew during aging is believed to depend on several
      intrinsic (cell-autonomous) and extrinsic (non-cell-autonomous) factors. In this
      review, we focus on how dysregulation of reactive oxygen species (ROS) and
      disruptions of genomic stability can impair HSC functions. Recently, it was shown
      that long-term self-renewing HSCs normally possess low levels of intracellular
      ROS. However, when intracellular ROS levels become excessive, they cause
      senescence or apoptosis, resulting in a failure of HSC self-renewal. Repression
      of intracellular ROS levels in HSCs by treatment with an antioxidant that
      scavenges ROS can rescue HSC functions, indicating that excess ROS levels are at
      the root of HSC failure. Products of numerous genes that are involved in either
      DNA-damage responses or longevity-related signaling contribute to the maintenance
      of the HSC self-renewal capacity. Further investigations on the molecular
      mechanisms of ROS regulation and on the manipulation of excess ROS levels could
      lead to the development of novel therapeutics for hematopoietic diseases,
      regenerative medicine, and the prevention of leukemia.

PMID- 18627346
TI  - Oxidative stress impairs endothelial progenitor cell function.
AB  - Circulating endothelial progenitor cells (EPCs) in adult human peripheral blood
      were identified in 1997. Since their original identification, EPCs have been
      extensively studied as biomarkers to assess the risk of cardiovascular disease in
      human subjects and as a potential cell therapeutic for vascular regeneration.
      EPCs are exposed to oxidative stress during vascular injury as residents of blood
      vessel walls or as circulating cells homing to sites of neovascularization. Given
      the links between oxidative injury, endothelial cell dysfunction, and vascular
      disease, recent investigation has focused on the responses of EPCs to oxidant
      stress and the molecular mechanisms that control redox regulation in these
      specialized cells. In this review, we discuss the various cell and flow
      cytometric techniques used to define and isolate EPCs from circulating blood and
      the current human and mouse genetic data, which offer insights into redox control
      in EPC biology and angiogenesis. Finally, we review how EPC responses to oxidant
      stress may be a critical determinant in maintaining the integrity and function of
      the cardiovascular system and how perturbations of redox control in EPCs may lead
      to various human diseases.

PMID- 18627348
TI  - Oxidative stress in Fanconi anemia hematopoiesis and disease progression.
AB  - Patients with the genomic instability syndrome Fanconi anemia (FA) commonly
      develop progressive bone marrow failure and have a high risk of cancer. The
      prominent role of the FA protein family involves DNA damage response and/or
      repair. Oxidative stress, defined as an imbalance between the production of
      reactive oxygen species and antioxidant defense, is considered to be an important
      pathogenic factor in leukemia-prone bone marrow diseases such as FA. Cellular
      responses inducing resistance to oxidative stress are important for cellular
      survival, organism lifespan, and cancer prevention, but until recently, mammalian
      factors regulating resistance to oxidative stress have not been well
      characterized. Significant evidence supports excessive apoptosis of hematopoietic
      stem/progenitor cells, induced by stresses, most significantly oxidative stress,
      as a critical factor in the pathogenesis of bone marrow failure and leukemia
      progression in FA. In this brief review, we discuss the functional link between
      FA proteins and oxidative DNA damage response/repair, with emphasis on the
      implication of oxidative stress in the pathophysiology and abnormal hematopoiesis
      in FA.

PMID- 18627351
TI  - A requirement for thioredoxin in redox-sensitive modulation of T-cadherin
      expression in endothelial cells.
AB  - T-cad (T-cadherin), a glycosylphosphatidylinositol-anchored cadherin superfamily
      member, is expressed widely in the brain and cardiovascular system, and absent,
      decreased, or even increased, in cancers. Mechanisms controlling T-cad expression
      are poorly understood. The present study investigated transcriptional regulation
      of T-cad in ECs (endothelial cells). Conditions of oxidative stress (serum
      deprivation or presence of H(2)O(2)) elevate T-cad mRNA and protein levels in
      ECs. Reporter gene analysis, using serially deleted T-cad promoter stretches
      ranging from -99 to -2304 bp, located the minimal promoter region of T-cad within
      -285 bp from the translation start site. Reporter activity in ECs transfected
      with the -285 bp construct increased under conditions of oxidative stress, and
      this was normalized by antioxidant N-acetylcysteine. An electrophoretic-mobility
      shift assay revealed a specific nucleoprotein complex unique to -156 to -203 bp,
      which increased when nuclear extracts from oxidatively stressed ECs were used,
      suggesting the presence of redox-sensitive binding element(s). MS analysis of the
      nucleoprotein complex unique to -156 to -203 bp after streptavidin-agarose pull
      down detected the presence of the redox-active protein thioredoxin. The presence
      of thioredoxin-1 in a nuclear extract from oxidatively stressed ECs was
      demonstrated after immunoprecipitation and immunoblotting. Transfection of ECs
      with thioredoxin-1 small interfering RNA abrogated oxidative-stress-induced up
      regulation of T-cad transcripts and protein. We conclude that thioredoxin-1 is an
      important determinant of redox-sensitive transcriptional up-regulation of T-cad
      in ECs.

PMID- 18627349
TI  - Hyperoxia, endothelial progenitor cell mobilization, and diabetic wound healing.
AB  - Diabetic foot disease is a major health problem, which affects 15% of the 200
      million patients with diabetes worldwide. Diminished peripheral blood flow and
      decreased local neovascularization are critical factors that contribute to the
      delayed or nonhealing wounds in these patients. The correction of impaired local
      angiogenesis may be a key component in developing therapeutic protocols for
      treating chronic wounds of the lower extremity and diabetic foot ulcers.
      Endothelial progenitor cells (EPCs) are the key cellular effectors of postnatal
      neovascularization and play a central role in wound healing, but their
      circulating and wound-level numbers are decreased in diabetes, implicating an
      abnormality in EPC mobilization and homing mechanisms. The deficiency in EPC
      mobilization is presumably due to impairment of eNOS-NO cascade in bone marrow
      (BM). Hyperoxia, induced by a clinically relevant hyperbaric oxygen therapy (HBO)
      protocol, can significantly enhance the mobilization of EPCs from the BM into
      peripheral blood. However, increased circulating EPCs failed to reach to wound
      tissues. This is partly a result of downregulated production of SDF-1alpha in
      local wound lesions with diabetes. Administration of exogenous SDF-1alpha into
      wounds reversed the EPC homing impairment and, with hyperoxia, synergistically
      enhanced EPC mobilization, homing, neovascularization, and wound healing.

PMID- 18627352
TI  - Shifting from clonal to sexual reproduction in aphids: physiological and
      developmental aspects.
AB  - Developmental biology is one of the fastest growing and fascinating research
      fields in life sciences. Among the wide range of embryonic development, a
      fundamental difference exists between organisms with sexual or asexual
      development. Aphids are unusual organisms which display alternative pathways of
      sexual and asexual development, the orientation of the pathway being determined
      by environmental conditions. These insects offer an adapted system in which to
      study developmental plasticity, because a side-by-side comparison of sexual and
      asexual development can be made in individuals with the same genotype. In this
      review, we describe the developmental mechanisms that have evolved in aphids for
      alternative sexual and asexual reproduction. In particular, we discuss how
      environmental cues orientate the reproductive mode of aphids from signal
      perception to endocrine regulation, and propose a comparative analysis of sexual
      and asexual gametogenesis and embryogenesis, which has been possible due to the
      development of molecular methods. As a result of the recent development of
      genomic resources in aphids, we expect these species will permit major advances
      in the study of the genomic basis underlying the choice of developmental fate and
      multiple reproduction strategies.

PMID- 18627353
TI  - Viral detection by electron microscopy: past, present and future.
AB  - Viruses are very small and most of them can be seen only by TEM (transmission
      electron microscopy). TEM has therefore made a major contribution to virology,
      including the discovery of many viruses, the diagnosis of various viral
      infections and fundamental investigations of virus-host cell interactions.
      However, TEM has gradually been replaced by more sensitive methods, such as the
      PCR. In research, new imaging techniques for fluorescence light microscopy have
      supplanted TEM, making it possible to study live cells and dynamic interactions
      between viruses and the cellular machinery. Nevertheless, TEM remains essential
      for certain aspects of virology. It is very useful for the initial identification
      of unknown viral agents in particular outbreaks, and is recommended by regulatory
      agencies for investigation of the viral safety of biological products and/or the
      cells used to produce them. In research, only TEM has a resolution sufficiently
      high for discrimination between aggregated viral proteins and structured viral
      particles. Recent examples of different viral assembly models illustrate the
      value of TEM for improving our understanding of virus-cell interactions.

PMID- 18627350
TI  - Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in
      cancer and endothelial cells: small-molecule inhibition of the redox function of
      Ape1.
AB  - The DNA base excision-repair pathway is responsible for the repair of DNA damage
      caused by oxidation/alkylation and protects cells against the effects of
      endogenous and exogenous agents. Removal of the damaged base creates a baseless
      (AP) site. AP endonuclease1 (Ape1) acts on this site to continue the BER-pathway
      repair. Failure to repair baseless sites leads to DNA strand breaks and
      cytotoxicity. In addition to the repair role of Ape1, it also functions as a
      major redox-signaling factor to reduce and activate transcription factors such as
      AP1, p53, HIF-1alpha, and others that control the expression of genes important
      for cell survival and cancer promotion and progression. Thus, the Ape1 protein
      interacts with proteins involved in DNA repair, growth-signaling pathways, and
      pathways involved in tumor promotion and progression. Although knockdown studies
      with siRNA have been informative in studying the role of Ape1 in both normal and
      cancer cells, knocking down Ape1 does not reveal the individual role of the redox
      or repair functions of Ape1. The identification of small-molecule inhibitors of
      specific Ape1 functions is critical for mechanistic studies and translational
      applications. Here we discuss small-molecule inhibition of Ape1 redox and its
      effect on both cancer and endothelial cells.

PMID- 18627354
TI  - Construction and evaluation of a maize (Zea mays) chimaeric promoter with
      activity in kernel endosperm and embryo.
AB  - Chimaeric promoters contain DNA sequences from different promoters. Chimaeric
      promoters are developed to increase the level of recombinant protein expression,
      to precisely control transgene activity or to combat homology-based gene
      silencing. Sets of chimaeric promoters, each containing different lengths of DNA
      from maize (Zea mays) 27zn (27 kDa gamma-zein) endosperm-specific promoter and
      the Glb1 (Globulin-1) embryo-specific promoter were created and tested in a
      transient expression assay of GFP (green fluorescent protein). Promoter fragments
      with the highest activity were combined to create the chimaeric promoter
      A27znGlb1. In the context of the chimaeric promoter, the selected Glb1 promoter
      fragment was necessary and sufficient to activate expression in embryo tissue and
      was functionally equivalent to the native Glb1 promoter. Similarly, the selected
      27zn promoter fragment in the chimaeric promoter was necessary and sufficient to
      activate expression in endosperm tissue and was functionally equivalent to the
      native 27zn promoter. Maize transgenic plants containing the A27znGlb1 chimaeric
      promoter fused to GFP were produced to characterize this promoter in vivo.
      Quantitative reverse-transcriptase PCR was used to determine that the promoter
      was active in the embryo, endosperm, pericarp and immature leaf tissues. GFP
      activity in plants containing the chimaeric promoter was not significantly
      different in endosperm than the activity of GFP fused to the full-length 27zn
      promoter, nor was it different in embryo from the activity of GFP fused to the
      full-length Glb1 promoter. Transgene copy numbers were shown to be between 4 and
      12 copies in different events.

PMID- 18627355
TI  - Establishment of hapten-specific monoclonal avian IgY by conversion of antibody
      fragments obtained from combinatorial libraries.
AB  - Nowadays, recombinant antibody and phage display technology enable the efficient
      generation of immunotools and a subsequent manipulation for optimized affinity,
      specificity or overall performance. Such advantages are of particular interest
      for haptenic target structures, such as TNT (2,4,6-trinitrotoluene). The toxicity
      of TNT and its breakdown products makes a reliable and fast detection of low
      levels in aqueous samples highly important. In the present study, we aimed for
      the generation of scFvs (single-chain antibody fragments) specific for the TNT
      surrogate TNP (2,4,6-trinitrophenyl) and their subsequent production as
      monoclonal avian IgY immunoglobulins providing improved assay performance.
      Therefore we subjected a human synthetic scFv library to selection following
      different strategies. TNP-specific human antibody fragments could be identified,
      characterized for their primary structure and evaluated for production as soluble
      scFv in Escherichia coli. Additionally, a murine TNP-specific antibody fragment
      was obtained from the hybridoma 11B3; however, the prokaryotic expression level
      was found to be limited. To generate and evaluate immunoglobulin formats with
      superior characteristics, all recombinant antibody fragments then were converted
      into two different chimaeric bivalent IgY antibody formats. After expression in
      mammalian cells, the IgY antibodies were assessed for their reactivity towards
      TNT. The IgY antibodies generated on the basis of the combinatorial library
      proved to be useful for detection of TNT, thereby emphasizing the high potential
      of this approach for the development of detection devices for immunoassay-based
      techniques.

PMID- 18627356
TI  - Normal brainstem responses in moderately preterm infants.
AB  - AIM: The aim of this study was to detect any differences in brainstem auditory
      evoked responses (BAERs) to different click rates between moderately preterm and
      term infants. METHODS: BAER was recorded with 21-91/s clicks at term age (37-42
      weeks postconceptional age) in 39 moderately preterm infants (gestation 33-36
      weeks). The results were compared with 37 healthy term infants. RESULTS: The
      latencies of waves I, III and V, and I-V interval in preterm infants were all
      similar to term infants at all click rates. The I-III interval decreased slightly
      and differed from term infants at 91/s (ANOVA, p < 0.05), while the III-V
      interval increased slightly. The III-V/I-III interval ratio increased slightly
      and differed from term infants at 91/s (p < 0.05). Wave amplitudes were similar
      in the two groups of infants, except an increase in wave V amplitude at 91/s in
      preterm infants (p < 0.05). No significant differences were found in BAER click
      rate-dependent changes between the two groups. CONCLUSION: No marked differences
      were found in BAER at any click rates at term age between moderately preterm and
      term infants, suggesting that moderately preterm birth does not have a marked
      effect on neonatal BAER. BAER normal data and criteria from term infants can
      generally be used for moderately preterm infants.

PMID- 18627357
TI  - Hypercapnia and the neonate.
AB  - 'Permissive hypercapnia' is a familiar term in neonatal intensive care, given the
      widespread adoption of low-tidal-volume ventilation strategies applied with the
      goal of decreasing respiratory morbidity. Recent evidence suggesting that
      hypercapnic acidosis may itself have protective effects on the lung and other
      organs has led to the coining of a new phrase, 'therapeutic hypercapnia', which
      also encompasses the use of supplemental inspired CO(2). CONCLUSION: Experimental
      evidence suggests that mild-moderate hypercapnia can improve tissue oxygenation
      and perfusion, which may ameliorate injury to the immature lung and brain.
      However, hypercapnia may also be associated with adverse outcomes, and the range
      of PaCO(2) levels that are both safe and effective for specific subsets of
      neonates has yet to be determined.

PMID- 18627358
TI  - Activation of the right fronto-temporal cortex during maternal facial recognition
      in young infants.
AB  - BACKGROUND/AIM: Within the first days of life infants can already recognize their
      mother. This ability is based on several sensory mechanisms and increases during
      the first year of life, having its most crucial phase between 6 and 9 months when
      cortical circuits develop. The underlying cortical structures that are involved
      in this process are still unknown. Herein we report how the prefrontal cortices
      of healthy 6- to 9-month-old infants react to the sight of their mother's faces
      compared to that of an unknown female face. METHODS: Concentrations of oxygenated
      haemoglobin [HbO2] and deoxygenated haemoglobin [HHb] were measured using near
      infrared spectroscopy (NIRS) in both fronto-temporal and occipital areas on the
      right side during the exposure to maternal and unfamiliar faces. RESULTS: The
      infants exhibited a distinct and significantly higher activation-related
      haemodynamic response in the right fronto-temporal cortex following exposure to
      the image of their mother's face, [HbO2] (0.75 micromol/L, p < 0.001), as
      compared to that of an unknown face (0.25 micromol/L, p < 0.001). CONCLUSION:
      Event-related haemodynamic changes, suggesting cortical activation, in response
      to the sight of human faces were detected in 6- to 9-month old children. The
      right fronto-temporal cortex appears to be involved in face recognition processes
      at this age.

PMID- 18627359
TI  - Voluntary ethanol intake enhances excitatory synaptic strength in the ventral
      tegmental area.
AB  - BACKGROUND: Addiction has been considered a disorder of motivational control over
      behavior, and the ventral tegmental area (VTA), in conjunction with other limbic
      brain structures, is thought to play a critical role in the regulation of a
      number of motivated behaviors including seeking of addictive drugs such as
      alcohol. Of particular interest is the ability of prolonged exposure of addictive
      drugs to enhance the function of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)-type glutamatergic receptors (AMPAR) in the VTA,
      as glutamate receptor activation can significantly regulate VTA neuron activity.
      Here, we examined whether voluntary ethanol intake altered VTA AMPAR function.
      METHODS: We utilized in vitro electrophysiology to examine glutamatergic function
      in the VTA neurons 12 to 24 hours after the last self-administration bout, which
      occurred 35 to 50 days after the initiation of ethanol self-administration under
      a 2-bottle intermittent access model. RESULTS: Voluntary intermittent ethanol
      intake in a 2-bottle paradigm enhanced postsynaptic AMPAR function, indicated by
      an increased ratio of evoked AMPAR to N-methyl-d-aspartic acid receptor currents,
      and by an increase in the amplitude of spontaneous miniature excitatory
      postsynaptic currents (mEPSCs) measured in the presence of tetrodotoxin to
      prevent action potential-dependent release. In contrast, ethanol self
      administration did not alter evoked presynaptic glutamate release, indicated by
      no change in the paired-pulse ratio of 2 AMPAR EPSCs evoked 50 ms apart, although
      spontaneous glutamate release was significantly enhanced, indicated by enhanced
      mEPSC frequency. CONCLUSIONS: Our results suggest that postsynaptic AMPAR
      function in VTA neurons was significantly enhanced after ethanol self
      administration. As increased VTA AMPAR function can significantly regulate firing
      and enhance the reinforcing and activating effects of drugs of abuse, the
      increased AMPAR activity observed here may facilitate the drive to consume
      ethanol.

PMID- 18627360
TI  - Ethanol-induced malfunction of neutrophils respiratory burst on patients
      suffering from alcohol dependence.
AB  - BACKGROUND: Polymorphonuclear, neutrophil granulocytes (PMN) play a major role in
      the control of infections, and people who abuse alcohol are susceptible to
      infections. Resistance against infections ensues intracellularly following
      initial phagocytosis of microorganisms with the oxygen-dependent respiratory
      burst, the key enzyme of which is the respiratory burst oxidase, whereby oxygen
      radicals are produced for microbial destruction. To date there is insufficient
      information available in connection with the process of impaired defence against
      infection in patients suffering from alcohol dependence. Therefore, our
      investigation was carried out to determine the influence of alcohol exposition on
      the formation of oxygen radicals and the respiratory burst. METHODS: 4.5 ml of
      whole blood was taken from 10 healthy adults and 10 patients suffering from
      alcohol dependence. An additional 3.5 ml of whole blood was taken from the
      alcoholic patients for determination of the blood alcohol concentration. The
      respiratory burst of PMN was tested using the Four-Colour-Continuous Flow
      Cytometer. Each experimental procedure consisted of 4 test samples [negative
      controls, Escherichia coli, FMLP-supplement (N-formyl-l-methionyl-l-leucyl-l
      phenylalanin), PMA-supplement (phorbol-12-myristate-13-acetate)]. Differing
      concentrations of ethanol were also introduced to each of the tests performed
      (0.20 to 4.00 g/l). RESULTS: Ethanol revealed a marked decrease of burst activity
      in those patients suffering from alcoholism with increased alcohol concentration.
      A dependence between the burst activity and the ethanol concentration was seen to
      be statistically significant. This effect was only evident after stimulation with
      E. coli and FMLP in those patients with alcohol dependence. CONCLUSION: The
      results presented in this study show an impairment in the function of PMN in
      those patients addicted to alcohol due to the decrease in burst activity. In view
      of the results of the different stimuli, the second-messenger effects were not
      evident. A clarification of this phenomenon could well be assumed as an
      allosteric receptor effect on the burst oxidase, namely, a direct effect on the
      phagocytosis interaction between circulating granulocytes and causative
      organisms.

PMID- 18627361
TI  - The Healthy Moms Study: the efficacy of brief alcohol intervention in postpartum
      women.
AB  - BACKGROUND: The prevention and treatment of alcohol use disorders among women of
      reproductive age have been well described. However, there is limited information
      on women specifically during the postpartum period. This period in a woman's life
      is a time of transition and it provides an ideal opportunity for primary care
      providers to intervene. PURPOSE: The goal of this report was to present the
      results of a brief alcohol intervention conducted in 34 obstetrical practices
      with women seeking routine postpartum care. METHODS: A randomized clinical trial
      was conducted from 2002 to 2005 in a diverse sample of women located in 15
      Wisconsin counties. This report presents 6-month follow-up data. RESULTS: A total
      of 8,706 women were screened for high-risk alcohol use during routine postpartum
      care with 997 (12%) of these women testing positive for at-risk drinking. A total
      of 235 women met inclusion criteria and were randomized to either "usual care" or
      "brief intervention." The 4-session intervention was delivered by outpatient
      obstetrical nurses and research staff. The mean age of the women in the sample
      was 28, 19.3% were from minority groups, 60.8% were married, 53.2% reported
      current tobacco use, and 17.9% had used marijuana in the previous 30 days. At the
      6 month follow-up appointment, there were significant reductions in mean number
      of total drinks in the previous 28 days (p < 0.013), number of drinking days (p <
      0.024) and heavy drinking days (p < 0.019). In addition to a statistical
      difference between groups, there was a 19% difference in the mean number of
      drinks and number of drinking days, and a 36% difference in the number of heavy
      drinking days in favor of the intervention group. CONCLUSION: The findings of the
      Healthy Moms Trial support the implementation of brief alcohol intervention
      during the postpartum period.

PMID- 18627362
TI  - Review article: new drug formulations, chemical entities and therapeutic
      approaches for the management of ulcerative colitis.
AB  - BACKGROUND: Treatment options for ulcerative colitis (UC) are expanding with the
      development of novel drug formulations and dosing regimens and new chemical
      entities. Although the goals of medical therapy for UC remain unchanged, that is
      to induce and to maintain remission, focus has also centred on improving patient
      compliance, modifying the natural course of disease and healing the mucosa. AIM:
      To examine novel formulations, new chemical entities and novel therapeutic
      approaches to the management of UC. METHODS: Searches for all studies related to
      UC treatment in Medline and abstracts from major national and international
      meetings published in the last 10 years. RESULTS: 5-Aminosalicylic acids (5-ASA)
      remain the standard first-line treatment for patients with mild to moderately
      active UC. New formulations with altered delivery, and new dosing regimens have
      demonstrated possible improvements in efficacy compared with historically
      available preparations and dosing patterns. Once-daily dosing, micropellet
      formulations,and high-dose tablets offer enhanced efficacy and improved
      compliance. 5-ASA is now recognized as a ligand for peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) and it has a role as a chemo-preventive
      agent in long-standing UC. New colonic release corticosteroid formulations help
      to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown
      promising results. New anti-inflammatory targeted therapies include an anti-CD3
      antibody, selective integrin blockers, anti-IL-2 antibody and PPAR-gamma
      agonists. CONCLUSION: The evolution of novel oral 5-ASA formulations and dosage
      regimens,and recent development of new molecules have expanded the therapeutic
      armamentarium of UC.

PMID- 18627363
TI  - Clinical trial: randomized controlled study of zidovudine and lamivudine for
      patients with primary biliary cirrhosis stabilized on ursodiol.
AB  - BACKGROUND: A human betaretrovirus has been characterized in patients with
      primary biliary cirrhosis (PBC). Uncontrolled studies using combination anti
      retroviral therapy have reported significant biochemical and histological
      improvement. AIM: To conduct a double blind, randomized controlled trial as a
      proof of principal to link infection with PBC. METHODS: Fifty-nine patients with
      an alkaline phosphatase level>1.5 upper limits of normal stabilized on
      ursodeoxycholic acid therapy were randomized to either 300 mg zidovudine and 150
      mg lamivudine B.I.D. or placebo for 6 months. RESULTS: None of the patients
      normalized alkaline phosphatase and no significant differences were observed in
      normalizing serum aminotransferase levels. Significant differences were observed
      in the antiviral versus placebo arms with improvements in serial alkaline
      phosphatase (p<0.04), ALT (p<0.03) and AST (p<0.04) as well as clinical score
      (p<0.02). After 6 months, 25% of patients in the placebo arm and 4% in the
      antiviral arm had evidence of virus in serum. CONCLUSIONS: The study endpoints
      for normalizing hepatic biochemistry were too stringent to show efficacy for
      zidovudine and lamivudine therapy despite the demonstrable impact on clinical and
      biochemical improvement. Accordingly, more potent anti-viral regimens will be
      required to confirm the efficacy of antiviral therapy in PBC patients with human
      betaretrovirus infection.

PMID- 18627364
TI  - Review article: the therapeutic and prognostic benefit of portal pressure
      reduction in cirrhosis.
AB  - BACKGROUND: Hepatic venous pressure gradient (HVPG) measurement is not a
      routinely used technique, despite its therapeutic and prognostic value. AIM: To
      review the role of HVPG from published literature. METHODS: Systematic literature
      review. RESULTS: In acute variceal bleeding, HVPG is prognostic identifying
      'difficult to treat' group, which now has defined clinical correlations. In
      secondary prevention of portal hypertensive bleeding, a reduction to < or = 12
      mmHg confers near complete protection against rebleeding. The target of > or =
      20% HVPG reduction from baseline needs prospective assessment to test a change of
      therapy, if no reduction occurs. The acute HVPG response to beta-blockade needs
      further assessment. In primary prevention, the cost-effectiveness of HVPG
      measurement is not favourable given the efficacy of medical therapy. In chronic
      liver disease, wedge hepatic venous pressure (WHVP) is prognostic for survival.
      Pharmacological reduction in portal pressure decreases complications and improves
      survival, possibly independent of a concomitant improvement in liver function.
      This latter requires urgent confirmation as it is clinically very relevant. HVPG
      monitoring can be used to assess anti-viral therapy particularly in cirrhosis,
      ergonomically combined with transjugular biopsy. CONCLUSIONS: The prognostic and
      therapeutic value of HVPG is established beyond portal hypertensive bleeding for
      which there are some clinical surrogates. HVPG measurement should now be part of
      everyday clinical practice.

PMID- 18627366
TI  - Modelling patient flows as an aid to decision making for critical care capacities
      and organisation.
AB  - Using real data from a number of hospitals, we predicted the patient flows
      following a capacity or organisational change. Clinically recognisable patient
      groups obtained through classification and regression tree analysis were used to
      tune a simulation model for the flow of patients in critical care units. A tuned
      model which accurately reflected the base case of the flow of patients was used
      to predict alterations in service provision in a number of scenarios which
      included increases in bed numbers, alterations in patients' lengths of stay,
      fewer delayed discharges, caring for long stay patients outside the formal
      intensive care unit and amalgamating small units. Where available the
      predictions' accuracy was checked by comparison with real hospital data collected
      after an actual capacity change. The model takes variability and uncertainty
      properly into account and it provides the necessary information for making better
      decisions about critical care capacity and organisation.

PMID- 18627367
TI  - A procedure-specific systematic review and consensus recommendations for
      postoperative analgesia following total knee arthroplasty.
AB  - The PROSPECT Working Group, a collaboration of anaesthetists and surgeons,
      conducts systematic reviews of postoperative pain management for different
      surgical procedures (http://www.postoppain.org). Evidence-based consensus
      recommendations for the effective management of postoperative pain are then
      developed from these systematic reviews, incorporating clinical practice
      observations, and transferable evidence from other relevant procedures. We
      present the results of a systematic review of pain and other outcomes following
      analgesic, anaesthetic and surgical interventions for total knee arthroplasty
      (TKA). The evidence from this review supports the use of general anaesthesia
      combined with a femoral nerve block for surgery and postoperative analgesia, or
      alternatively spinal anaesthesia with local anaesthetic plus spinal morphine. The
      primary technique, together with cooling and compression techniques, should be
      supplemented with paracetamol and conventional non-steroidal anti-inflammatory
      drugs or COX-2-selective inhibitors, plus intravenous strong opioids (high
      intensity pain) or weak opioids (moderate- to low-intensity pain).

PMID- 18627368
TI  - The effects of interrupted or continuous administration of sevoflurane on
      preconditioning before cardio-pulmonary bypass in coronary artery surgery:
      comparison with continuous propofol.
AB  - Volatile anaesthetics have been shown to exert cardioprotective properties in
      experimental and clinical studies. However, the mode of administration may
      influence these cardioprotective effects. The present study was designed to
      compare the effect of interrupted administration of sevoflurane before
      cardiopulmonary bypass with continuous sevoflurane administration and with
      propofol-only anaesthesia, on cardioprotection as assessed by left ventricular
      performance and myocardial cell damage during coronary artery bypass grafting.
      Forty-two patients scheduled for coronary bypass surgery were randomly assigned
      to one of three groups: propofol-only (P; n = 14), continuous (SevoC; n = 14) and
      interrupted sevoflurane administration (SevoI; n = 14). Myocardial cell damage as
      assessed by Troponin T (cTNT) and creatine kinase MB (CK-MB) were chosen as the
      primary endpoints and echocardiographic myocardial performance index (MPI)
      measurements were also performed. Up to 48 h postoperatively, in group SevoI,
      postoperative cTNT values (mean (SD) 0.13 (0.04) ng x ml(-1)) were significantly
      (p < 0.05) lower than both the P (0.26 (0.31) ng x ml(-1)) and SevoC (0.25 (0.17)
      ng x ml(-1)) groups. CK-MB levels were also significantly (p < 0.05) lower in the
      SevoI group at 24 h after surgery and MPI significantly improved compared with
      both the P and SevoC groups. There was, however, no difference with respect to
      cytokine release and length of stay in either the intensive care unit or in the
      hospital. We conclude that prior interrupted sevoflurane administration confers
      some cardioprotection as compared with continuous sevoflurane administration or
      propofol-based anaesthesia.

PMID- 18627369
TI  - HMBS mutations in Chinese patients with acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP), an autosomal dominant disorder, is caused by
      partial deficiency of hydroxymethylbilane synthase (HMBS) affecting heme
      biosynthesis. Patients with AIP are characterized by recurrent abdominal pain,
      port-wine urine, and motor paresis. The disease can be provoked by changes in
      hormone levels, drugs and fasting. Molecular analysis for twenty-four unrelated
      Chinese AIP patients from Taiwan identified twenty-five HMBS mutations. There
      were 10 missense (40%), four nonsense (16%), five frame-shift (20%) and six
      splice site (24%) mutations. More than a half (15/25, 60%) of these mutations are
      predicted to produce a truncated protein. Four (c.33 + 5C>A, Arg26Cys, Arg26His,
      Arg325X) occurred more than once among the 24 families and one individual carried
      two mutations in the same allele, a missense (Gly221Asp) and a splice site
      mutation (c.652-1G>A). Of the 25 mutations, eleven were novel (Arg149Pro,
      Gly218Arg, Asn322X, Gly221Asp, Pro313X, c.88-4_-16delAAGTCTCTACCCG,
      c.1008_1019delCAGCCTGGCCAA, c.113delT, c.88-4_-16delAAGTCTCTACCCGinsCA,
      c.160delA, c.902_909delTCCCTGCC). No correlation between genetic defect and
      phenotype (both clinical and biochemical) was observed in this study.

PMID- 18627370
TI  - Hidradenitis suppurativa: are tumour necrosis factor-alpha blockers the ultimate
      alternative?

PMID- 18627371
TI  - Angiolymphoid hyperplasia with eosinophilia affecting the penis.

PMID- 18627372
TI  - Efficacy and tolerability of biologic and nonbiologic systemic treatments for
      moderate-to-severe psoriasis: meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The comparative efficacy and tolerability of conventional and
      biologic treatments for moderate-to-severe plaque psoriasis are unknown.
      OBJECTIVES: To perform a systematic review and meta-analysis of randomized
      controlled trials (RCTs) reporting efficacy of systemic treatments approved for
      moderate-to-severe psoriasis by means of the Psoriasis Area and Severity Index
      (PASI). METHODS: We identified relevant articles by systematic electronic
      searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as
      proportion of participants with >or= 75% decrease in PASI (PASI-75) at primary
      efficacy measurement (week 8-16). PASI-75 response rates of double-blind placebo
      controlled trials were summarized as risk differences (RDs) and pooled using
      random effects models. Tolerability was assessed from rates of withdrawals and
      adverse events. RESULTS: Twenty-four RCTs totalling 9384 patients were analysed
      qualitatively. Sixteen double-blind placebo-controlled trials were eligible for
      meta-analysis. Infliximab was significantly superior to all other interventions
      [RD 77%, 95% confidence interval (CI) 72-81%]. Adalimumab (RD 64%, 95% CI 61-68%)
      was superior to ciclosporin (RD 33%, 95% CI 13-52%), efalizumab (RD 24%, 95% CI
      19-30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40-48%) and etanercept 25
      mg twice weekly (RD 30%, 95% CI 25-35%). Efalizumab was significantly less
      efficacious than fumaric acid esters (RD 48%, 95% CI 32-64%). Rates of
      withdrawals due to adverse events were highest for methotrexate and fumaric acid
      esters. CONCLUSIONS: The efficacy of systemic agents approved for moderate-to
      severe psoriasis differs considerably both within and between biologics and
      nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients
      receiving infliximab have an excess chance of 77% over placebo to achieve PASI-75
      response. Published evidence questions regulatory guidelines that recommend
      biologics as second-line therapy for moderate-to-severe plaque psoriasis.

PMID- 18627373
TI  - Analysis of 3-year national reimbursement application data on etanercept and
      efalizumab for psoriasis.

PMID- 18627374
TI  - Review and expert opinion on prevention and treatment of infliximab-related
      infusion reactions.
AB  - Infliximab (Remicade; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric
      monoclonal antibody that acts as a tumour necrosis factor-alpha inhibitor.
      Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic
      arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque
      type psoriasis. Like other foreign protein-derived agents, infliximab may lead to
      infusion reactions during and after infusion. Infusion reactions occur in 3-22%
      of patients with psoriasis treated with infliximab. Most of these reactions are
      mild or moderate and only few are severe. Nevertheless, they may lead to
      discontinuation of treatment. As infliximab for psoriasis is prescribed as a last
      resort and is in most cases very effective, discontinuation of treatment is
      undesirable. With proper care and prevention of the infusion reactions the need
      to discontinue treatment with infliximab can be diminished. The objective of this
      article is to present a guideline for the management of infliximab-related
      infusion reactions, based on the best available evidence. This guideline can be
      used in patients with psoriasis as well as in dermatology patients receiving
      infliximab for off-label indications such as hidradenitis suppurativa or pyoderma
      gangrenosum.

PMID- 18627375
TI  - Infliximab improves health-related quality of life in the presence of
      comorbidities among patients with moderate-to-severe psoriasis.
AB  - BACKGROUND: Psoriasis affects patients both physically and psychologically.
      OBJECTIVES: To investigate the effect of comorbidities on health-related quality
      of life (HRQoL) and to determine whether infliximab improved HRQoL in the
      presence of these conditions. METHODS: In this multicentre, double-blind study,
      835 patients with moderate-to-severe plaque psoriasis were randomized to receive
      infliximab 3 or 5 mg kg(-1) or placebo at weeks 0, 2 and 6. Infliximab-treated
      patients were re-randomized at week 14 to receive the same treatment every 8
      weeks or as needed through week 46; placebo patients crossed over to infliximab 5
      mg kg(-1) at week 16. Disease severity (Psoriasis Area and Severity Index, PASI)
      and HRQoL (Dermatology Life Quality Index, DLQI; 36-item Short-Form Health
      Survey, SF-36) were measured at various time points. The effect of patient
      comorbidities on baseline HRQoL was assessed using multiple regression models.
      The impact of key comorbidities on infliximab treatment effect was also assessed.
      RESULTS: Disease severity (PASI), depression and psoriatic arthritis (PsA) were
      predictors of poor baseline HRQoL. At week 10, infliximab 3 and 5 mg kg(-1)
      significantly improved physical and mental health dimensions of the SF-36 and the
      DLQI (all P < 0.001). Consistent improvement in HRQoL with infliximab treatment
      was observed regardless of baseline patient characteristics or comorbidities.
      Through week 50, HRQoL and PASI scores were most improved with infliximab 5 mg
      kg(-1) administered every 8 weeks. CONCLUSIONS: Disease severity, depression and
      PsA were significant predictors of poor HRQoL. Infliximab significantly improved
      HRQoL, regardless of these characteristics.

PMID- 18627376
TI  - Piezogenic palmar papules: a novel physical sign of palmar lipoma.

PMID- 18627377
TI  - Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in
      vitro and in vivo.
AB  - Cucurbitacins are a group of diverse triterpenoid substances isolated from plants
      with medicinal properties. One particularly potent family member is cucurbitacin
      B (CuB). The antiproliferative effects of CuB against human breast cancer cells
      were tested. Six human breast cancer cell lines were examined because they
      represent a diverse mix of breast cancer subtypes varying in expression of
      estrogen receptor (ER), Her2/neu, and p53 mutation. The antiproliferative effect
      of CuB were also studied in vivo. The effective dose inhibiting 50% growth
      (ED(50)) was between 10(-8) M and 10(-7) M for this collection of breast cancer
      cell lines. These cells underwent rapid morphologic changes after 15-20 min
      exposure to CuB (5 x 10(-7) M), which was associated with disruption of the
      microtubules and F-actin, as observed by confocal microscopy. Human MDA-MB-231
      (ER-, p53 mutated) breast cancer cells were orthotopically implanted into the
      breasts of nude mice who intraperitoneally received either CuB 1.0 mg/kg or
      vehicle. Tumor volume was reduced by 55% in the group that received CuB for 6
      weeks compared with vehicle controls. No apparent organ tissue damage was
      observed by pathological assessment. Interestingly, the experimental mice had
      lower serum glucose levels, consistent with use of CuB as an antidiabetic drug in
      China. This drug appears to be a third in a family of drugs targeting the
      microtubules (taxanes [e.g. taxol], vinca alkaloid [e.g. vincristine], and now
      CuB). Our in vitro and in vivo results suggest that CuB may be an effective, new
      approach for the treatment of ER-, Her2/neu amplified, and p53 mutant breast
      cancers.

PMID- 18627378
TI  - The head of Bartonella adhesin A is crucial for host cell interaction of
      Bartonella henselae.
AB  - Human pathogenic Bartonella henselae cause cat scratch disease and
      vasculoproliferative disorders (e.g. bacillary angiomatosis). Expression of
      Bartonella adhesin A (BadA) is crucial for bacterial autoagglutination, adhesion
      to host cells, binding to extracellular matrix proteins and proangiogenic
      reprogramming via activation of hypoxia inducible factor (HIF)-1. Like the
      prototypic Yersinia adhesin A, BadA belongs to the class of trimeric
      autotransporter adhesins and is constructed modularly consisting of a head, a
      long and repetitive neck-stalk module and a membrane anchor. Until now, the exact
      biological role of these domains is not known. Here, we analysed the function of
      the BadA head by truncating the repetitive neck-stalk module of BadA (B. henselae
      badA(-)/pHN23). Like B. henselae Marseille wild type, B. henselae badA(-)/pHN23
      showed autoagglutination, adhesion to collagen and endothelial cells and
      activation of HIF-1 in host cells. Remarkably, B. henselae badA(-)/pHN23 did not
      bind to fibronectin (Fn) suggesting a crucial role of the deleted stalk domain in
      Fn binding. Additionally, the recombinantly expressed BadA head adhered to human
      umbilical vein endothelial cells and to a lesser degree to epithelial (HeLa 229)
      cells. Our data suggest that the head represents the major functional domain of
      BadA responsible for host adhesion and angiogenic reprogramming.

PMID- 18627380
TI  - Endoparasitoid wasp bracovirus-mediated inhibition of hemolin function and
      lepidopteran host immunosuppression.
AB  - Successful embryonic development of parasitoid wasps in lepidopteran hosts is
      achieved through co-injection of polydna viruses whose gene products are thought
      to target the immune responses of the host. One gene product of the endosymbiont
      bracovirus of the parasitic wasp Cotesia rubecula, CrV1, has been reported to
      inhibit the immune responses of its endoparasitized lepidopteran host through
      interference with the haematocyte cytoskeletal structure. Here we establish that
      CcV1, the Cotesia congregata bracovirus orthologue of CrV1, is also uptaken by
      lepidopteran haemocytes and haemocyte-like established cell lines, but we also
      report on a different function of CcV1, which is highly relevant to the
      inhibition of the host immune responses and is based on its direct interaction
      with the pattern recognition molecule hemolin. Recombinant CcV1 inhibits hemolin
      functions, such as lipopolysaccharide binding and bacterial agglutination as well
      as bacterial phagocytosis by haemocytes and haemocyte-like cell lines, producing
      functional phenotypes equivalent to those observed to arise from RNAi-based
      inhibition of hemolin gene expression. Finally, we show that CcV1 and hemolin
      colocalize on the membrane surface of hemolin-expressing cells, a finding
      suggesting that CcV1 may be uptaken by haemocytes and inhibit haemocyte function
      as a result of its interaction with membrane-anchored hemolin.

PMID- 18627381
TI  - Cyclophosphamide-induced nail discoloration and skin hyperpigmentation: a rare
      presentation.

PMID- 18627379
TI  - Candida albicans transcription factor Rim101 mediates pathogenic interactions
      through cell wall functions.
AB  - pH-responsive transcription factors of the Rim101/PacC family govern virulence in
      many fungal pathogens. These family members control expression of target genes
      with diverse functions in growth, morphology and environmental adaptation, so the
      mechanistic relationship between Rim101/PacC and infection is unclear. We have
      focused on Rim101 from Candida albicans, which we find to be required for
      virulence in an oropharyngeal candidiasis model. Rim101 affects the yeast-hypha
      morphological transition, a major virulence requirement in disseminated infection
      models. However, virulence in the oropharyngeal candidiasis model is independent
      of the yeast-hypha transition because it is unaffected by an nrg1 mutation, which
      prevents formation of yeast cells. Here we have identified Rim101 target genes in
      an nrg1Delta/Delta mutant background and surveyed function using an
      overexpression-rescue approach. Increased expression of Rim101 target genes ALS3,
      CHT2, PGA7/RBT6, SKN1 or ZRT1 can partially restore pathogenic interaction of a
      rim101Delta/Delta mutant with oral epithelial cells. Four of these five genes
      govern cell wall structure. Our results indicate that Rim101-dependent cell wall
      alteration contributes to C. albicans pathogenic interactions with oral
      epithelial cells, independently of cell morphology.

PMID- 18627382
TI  - Maculopapular rash due to fluconazole.

PMID- 18627383
TI  - Pneumocystis carinii: name changed?

PMID- 18627384
TI  - Persistent lymphoedema in Morbihan disease: formation of perilymphatic
      epithelioid cell granulomas as a possible pathogenesis.
AB  - Morbihan disease is a rare complication of rosacea, characterized by persistent
      lymphoedema on the upper half of the face, occurring during the chronic clinical
      course of rosacea. This refractory condition has been also designated as 'rosacea
      lymphoedema' and 'solid persistent facial oedema of rosacea'. We report a patient
      with Morbihan disease showing persistent lymphoedema on the upper half of the
      face accompanied by unique histological findings of striking dermal dilated
      lymphatics and damage of the lymphatics at the site of the adjacent epithelioid
      cell granulomas, with histiocytes bulging into the lymphatic lumen. The marked
      epithelioid cell granulomas forming around dermal lymphatic vessels with
      subsequent lymphatic damage and luminal obstruction by histiocytic infiltration
      may account for the development of lymphoedema in this patient.

PMID- 18627385
TI  - Identification of a novel DSRAD gene mutation in a Chinese family with
      dyschromatosis symmetrica hereditaria.
AB  - Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant
      cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented
      macules of various sizes on the limbs. Genetic studies have identified mutations
      in the DSRAD gene, encoding double-stranded RNA-specific adenosine deaminase, to
      be responsible for this disorder. In this study, we identified a novel mutation
      of DSRAD gene in a Chinese family with DSH. The mutation is a novel heterozygous
      nucleotide T-->C transition at position 3617 in exon 15 of the DSRAD gene, which
      induces a M1206T change in the putative deaminase domain of DSRAD. Our study
      expands the database on the DSRAD gene mutations in DSH.

PMID- 18627386
TI  - Pyoderma gangrenosum associated with subcorneal pustular dermatosis and IgA
      myeloma.
AB  - We report a 57-year-old woman with a 12-year history of ulcerative pyoderma
      gangrenosum (PG). Five years after the onset of PG, she developed subcorneal
      pustular dermatosis (SPD) and biclonal IgA and IgG gammopathy. She developed PG
      at two bone-marrow biopsy sites, showing pathergy. Finally, she developed
      multiple myeloma. Although PG and SPD may occur without associated underlying
      malignancy, these patients should be followed up for any prospective malignancy
      because of the association between these disorders.

PMID- 18627387
TI  - Tufted hair folliculitis in a woman treated with lapatinib for breast cancer.

PMID- 18627388
TI  - A clinical study of patients with pemphigus vulgaris and pemphigus foliaceous: an
      11-year retrospective study (1996-2006).
AB  - Only a few reports have been published of detailed clinical studies of pemphigus
      in Japan. The aim of this study was to determine the clinical characteristics of
      patients with pemphigus vulgaris (PV) and pemphigus foliaceous (PF), who were
      newly diagnosed in the dermatology department of Kurume University Hospital,
      Japan, over the past 11 years. The primary site of involvement was the oral
      mucosa in 21 patients (75%) with PV. At the initial visit, most of the patients
      with PV had moderate to severe disease. With regard to management, systemic
      corticosteroids were the mainstay of treatment for patients with PV, and
      plasmapheresis was the most frequently used adjuvant therapy. Dapsone was the
      mainstay of treatment for the patients with PF. The patients were investigated
      for any association with an underlying malignancy; in patients with PV, lung,
      stomach and uterine cancers (one patient each) were seen.

PMID- 18627389
TI  - Is puncture skin test adequate to detect autoreactivity in patients with chronic
      urticaria?

PMID- 18627390
TI  - Follicular porokeratosis of Mibelli on the buttocks.
AB  - We report a case of follicular porokeratosis of Mibelli affecting the natal cleft
      in a 42-year-old white man. To our knowledge, this is the first report in the
      English-language literature of follicular porokeratosis of Mibelli limited to the
      genitogluteal area.

PMID- 18627391
TI  - Calciphylaxis in a patient with normal renal function: response to treatment with
      sodium thiosulfate.
AB  - Calciphylaxis is a rare, life-threatening cause of skin necrosis. The condition
      is primarily reported in patients with end-stage renal disease, and is associated
      with significant morbidity and mortality. Treatment has mainly been empirical. We
      report a case of calciphylaxis in a patient with normal renal function and
      hypoparathyroidism, who responded to treatment with sodium thiosulfate. To our
      knowledge, this is the first reported case of the use of sodium thiosulfate to
      treat calciphylaxis in a patient with normal renal function.

PMID- 18627392
TI  - Pigmented spots as a sign of mammary Paget's disease.
AB  - Pigmented mammary Paget's disease is a rare variant of mammary Paget's disease.
      The clinical appearance mimics malignant melanoma. This paper describes a case of
      asymptomatic, slightly pigmented spots on the right mammary nipple. The pigmented
      nipple was histopathologically diagnosed as mammary Paget's disease with an
      underlying intraductal carcinoma. This case suggests the importance of conducting
      skin biopsies of developing pigmented spots on the nipples in elderly people.

PMID- 18627393
TI  - Epidermolysis bullosa acquisita requiring multiple oesophageal dilatations.

PMID- 18627394
TI  - Photodynamic therapy for the treatment of morphoea.

PMID- 18627395
TI  - Cutaneous pemphigus vulgaris with skin features similar to the classic
      mucocutaneous type: a case report and review of the literature.
AB  - Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease
      that specifically involves oral mucosa. It was recently shown that a very small
      number of patients with PV show no mucous membrane involvement although they have
      circulating autoantibodies directed against both desmoglein (Dsg)1 and Dsg3 that
      are associated with histopathological suprabasal acantholysis. These cases are
      classed as cutaneous-type PV. We report here a case of cutaneous-type PV that
      occurred in a 50-year-old man. Clinical examination revealed numerous tense and
      spreading blisters and erosions over the patient's entire body, similar to the
      classic mucocutaneous-type PV. Interestingly, none of the previously reported
      patients with cutaneous PV had shown skin features like those of mucocutaneous
      PV, whereas the present case clearly demonstrated very typical clinical features
      similar to those in mucocutaneous PV.

PMID- 18627396
TI  - Nicolau's syndrome induced by intramuscular vaccinations in children: report of
      seven patients and review of the literature.
AB  - BACKGROUND: Nicolau's syndrome (NiS), or embolia cutis medicamentosa, is a rare
      condition characterized by the acute onset of cutaneous and soft-tissue necrosis
      following intramuscular drug injection. Intramuscular injections are the main
      route for vaccinations in children. METHODS: This is a retrospective study of
      seven children (mean age 9.8 months) who developed NiS subsequent to
      intramuscular vaccination. RESULTS: The reactions were observed after different
      combinations of vaccine antigens, and were no more common after repeated than
      after primary injection of the respective vaccine. Three children developed scars
      without functional impairment, two made a full recovery, and the final outcome is
      unknown for four. CONCLUSION: Given the high prevalence of intramuscular
      injections during infancy, NiS seems to be a rare event, but there is a
      possibility of under-reporting of less severe reactions. Our retrospective data
      do not allow a true risk assessment. The most worrying aspect of NiS, however, is
      its lack of predictability. As long as complete avoidance of the intramuscular
      route is not an option, it is obvious that NiS cannot be completely prevented.

PMID- 18627397
TI  - Pemphigus foliaceus induced by an angiotensin II receptor blocker.
AB  - A 76-year-old Korean woman presented with pruritic erythematous vesicles and
      crusted plaques over her entire body. She had been taking an angiotensin II
      receptor blocker (ARB) (candesartan) for 2 months before developing the skin
      lesions. The patients was diagnosed with pemphigus foliaceus based on the
      clinical and immunopathological criteria, including intra-epidermal bulla on skin
      histopathology, intercellular deposit of C(3) and IgG on direct
      immunofluorescence, and autoantibodies to the 160-kDa antigen on both immunoblot
      and ELISA. The medication was changed to another antihypertensive agent and the
      patient was treated with prednisolone for 2 months. The vesiculobullous skin
      lesions gradually disappeared. However, the skin lesions reappeared 2 months
      after starting a different ARB (telmisartan). This case illustrates the
      importance of taking a complete drug history in patients who present with bullous
      diseases. Furthermore, ARBs should be added to the list of nonthiol drugs that
      can possibly induce pemphigus.

PMID- 18627398
TI  - Differential expression of two new members of the p53 family, p63 and p73, in
      extramammary Paget's disease.
AB  - BACKGROUND: The proteins p53, p63 and p73 are known to be overexpressed and to
      play important roles in the pathogenesis of many tumours, but the expression of
      p63 and p73 has not previously been investigated in extramammary Paget's disease
      (EMPD). AIM: To investigate the potential contribution of p53, p63 and p73 in the
      pathogenesis of EMPD. METHODS: In total, 35 paraffin wax-embedded tissue samples
      from patients with EMPD were examined using immunohistochemical staining for p53,
      p63 and p73. RESULTS: All of the 35 EMPD specimens, including all 6 invasive EMPD
      and 2 metastatic lymph-node specimens, showed nuclear overexpression of both p53
      and p73. The expression levels (percentage of positive cells) of p53 and p73
      (90.66 +/- 12.53% and 80.20 +/- 13.07%) in EMPD were significantly higher than
      those of normal skin. There was a significant correlation between the expression
      levels of p53 and p73 in EMPD. In 29 of 35 EMPD specimens, there was no nuclear
      expression of p63, and weak or moderate staining was found in only 6 specimens.
      The expression level of p63 in EMPD was significantly less than that in normal
      skin. CONCLUSIONS: Our study shows that the concordant overexpression of p53 and
      p73 and the decreased expression of p63 may play a pivotal role in the
      pathogenesis of EMPD. The decreased expression of p63 may play a more important
      role in the pathogenesis of EMPD than the overexpression of p53 and p73.

PMID- 18627399
TI  - Contrasting human cytokine responses to promastigote whole-cell extract and the
      Leishmania analogue receptor for activated C kinase antigen of L. amazonensis in
      natural infection versus immunization.
AB  - It is known that the same antigen can induce different immune responses,
      depending upon the way that it is presented to the immune system. The objective
      of this study was to compare cytokine responses of peripheral blood mononuclear
      cells (PBMC) from cutaneous leishmaniasis patients and subjects immunized with a
      first-generation candidate vaccine composed of killed Leishmania amazonensis
      promastigotes to a whole-cell promastigote antigen extract (La) and to the
      recombinant protein LACK (Leishmania analogue receptor for activated C kinase),
      both from L. amazonensis. Thirty-two patients, 35 vaccinees and 13 healthy
      subjects without exposure to Leishmania, were studied. Cytokine production was
      assessed by enzyme-linked immunosorbent assay and enzyme-linked immunospot assay.
      The interferon (IFN)-gamma levels stimulated by La were significantly higher and
      the levels of interleukin (IL)-10 significantly lower than those stimulated by
      LACK in the patient group, while LACK induced a significantly higher IFN-gamma
      production and a significantly lower IL-10 production compared with those induced
      by La in the vaccinated group. LACK also induced a significantly higher frequency
      of IFN-gamma-producing cells than did La in the vaccinated group. The contrast in
      the cytokine responses stimulated by LACK and La in PBMC cultures from vaccinated
      subjects versus patients indicates that the human immune response to crude and
      defined Leishmania antigens as a consequence of immunization differs from that
      induced by natural infection.

PMID- 18627400
TI  - Addition of a total pancreatectomy and pancreas transplantation in a liver
      transplant recipient with intraductal papillary mucinous neoplasm of the
      pancreas.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are
      increasingly recognized in clinical practice. There are no published data
      suggesting a management approach for the potential organ transplant recipient
      with the incidental finding of this pre-malignant lesion. METHODS: The recipient
      was a 65-yr-old man with hepatocellular carcinoma in a background of Laennec's
      cirrhosis. During evaluation for transplant, he was found to have diffuse IPMN.
      This patient underwent liver transplantation with a planned simultaneous total
      native pancreatectomy and pancreas transplant from the same donor. RESULTS: The
      patient has had normal liver function and has been free of diabetes and exocrine
      insufficiency at 18 months post-transplant. CONCLUSION: IPMN in the potential
      transplant recipient should be managed more aggressively than in the general
      population because these patients will be committed to life-long
      immunosuppression. If a total pancreatectomy is contemplated, this is a unique
      opportunity to replace the pancreas with an allograft at the time of
      transplantation.

PMID- 18627401
TI  - Herpes zoster infection after liver transplantation in patients receiving
      induction therapy with alemtuzumab.
AB  - BACKGROUND: The incidence of herpes zoster (HZ) infection in liver transplant
      recipients prior to the use of induction therapy with monoclonal antibodies has
      been reported as being 1.2-18%. We studied the occurrence of HZ in liver
      transplant recipients that received induction therapy with alemtuzumab (Campath
      1H). MATERIAL AND METHODS: This was a retrospective review of primary liver
      transplant recipients who received alemtuzumab as induction therapy at our
      center. HZ infection was diagnosed clinically as the presence of a characteristic
      vesicular rash in a dermatomal distribution without any further virological
      confirmation. RESULTS: A total of 118 liver transplant recipients were treated
      with alemtuzumab between August 2002 and August 2005. Twelve patients developed
      HZ infection, and the cumulative probability of a patient developing HZ infection
      by 36 months post-transplant +/-1 SE was estimated as 16.5 +/- 5.0%. The median
      time for onset of the infection was 10.2 months (range 4.7-30.7) after the
      transplant. All patients had only one dermatomal distribution, and none developed
      systemic infection or complications such as postherpetic neuropathy. All patients
      except one were treated with systemic intravenous acyclovir. One patient received
      famciclovir. All of the patients had received ganciclovir during the post
      transplant period but were not receiving any other antiviral medication at the
      time of the infection. CONCLUSION: Herpes zoster infection has previously been
      reported as a frequent complication of liver transplantation. Our study suggests
      that it occurs in approximately 16% of patients receiving induction therapy with
      alemtuzumab. Although alemtuzumab is a powerful immunosuppressive agent and there
      is still little information regarding its long-term safety when used in liver
      transplantation, our data do not suggest any increase in the occurrence and
      complications of HZ.

PMID- 18627402
TI  - External ophthalmomyiasis by Oestrus ovis larvae diagnosed in a Papanicolaou
      stained conjunctival smear.

PMID- 18627403
TI  - Diagnostic value of clot examination for malignant cells in serous effusions.
AB  - OBJECTIVE: To assess the diagnostic value of clot examination for satisfactory
      processing and confirmation of malignancy in serous effusions in routine
      cytological evaluation and compare the results with those of conventional smear
      and cell block preparations. METHODOLOGY: Body cavity fluids (n = 600) received
      in our laboratory were processed according to a pre-designed protocol for the
      study as follows: Day1: on receipt of the specimen, smears were made and a cell
      block was prepared from the sediment. Day2: after overnight sample storage of the
      remaining specimen at 2-8 degrees C all fluids were examined for the presence of
      a clot at the bottom of the container. Fluids in which clot had formed were fixed
      in formalin. The clot was then placed on a lens paper, wrapped and processed
      routinely. Diagnostic yields were compared. RESULTS: In this study, we included
      600 cases of serous fluids from pleural, pericardial and peritoneal effusions. In
      73% (n = 437) of samples, clot formation was seen, while in 27%, (n = 163) no
      clot had formed. Routine smear and cell block preparations showed malignant cells
      in 9.6% (n = 42). However, with the addition of the clot preparation, the number
      of cases in which atypical/malignant cells were seen increased from 42 to 85
      (19.4%), with a P < 0.001. Special stains and immunohistochemistry (IHC) were
      also performed on clot preparations in 10 difficult cases. CONCLUSION: Clot
      preparation from body cavity fluids on the second day can be used as an adjunct
      to smear and routine cell block preparation to improve the accuracy and yield of
      the cytological diagnosis and may also be of great help for special studies such
      as IHC staining.

PMID- 18627404
TI  - Prospective study of urine cytology screening for BK polyoma virus replication in
      renal transplant recipients.
AB  - OBJECTIVE: BK virus (BKV) may be associated with interstitial nephritis in renal
      transplant recipients and this can lead to irreversible chronic allograft
      dysfunction. Early diagnosis of BKV nephropathy determines its progress because
      no specific antiviral therapy exists. Urine cytology, detection of viral DNA in
      urine or blood and renal biopsy are the main diagnostic tools. The purpose of
      this study was to evaluate the use of urine cytology for diagnosis of BKV
      replication in renal graft recipients. PATIENTS AND METHODS: We studied 32 de
      novo renal transplant recipients prospectively with sequential urine samples for
      a period of 1 year. Thin-Prep methodology was used to prepare the slides.
      Cytology results were correlated with polymerase chain reaction (PCR) in urine
      and blood. RESULTS: Decoy cells indicative of BKV infection were detected in 14
      (7.3%) of the 190 urine samples derived from 11 recipients. In three cases with
      positive decoy cells, BK viraemia and viruria were simultaneously identified. In
      a further three cases, BKV active replication was confirmed in urine by both
      cytology and PCR. CONCLUSIONS: Urine cytology is an easy and rapid method of
      detecting decoy cells in cases where renal biopsy is not possible. However, the
      low incidence of detection of decoy cells in the present study, together with
      poor correlation with PCR results, questions its sensitivity and specificity in
      diagnosing BKV reactivation.

PMID- 18627405
TI  - Cytodiagnosis of dedifferentiated liposarcoma clinically masquerading as a renal
      tumour.

PMID- 18627406
TI  - Diagnostic accuracy of fine-needle aspiration cytology in histological grade 1
      breast carcinomas: are we good enough?
AB  - BACKGROUND: Fine-needle aspiration cytology (FNAC) of both palpable and non
      palpable breast carcinomas has a high accuracy and sensitivity in dedicated
      centres. It is generally thought that low-grade carcinomas have a distinctly
      lower sensitivity due to discrete cellular atypia that may be difficult to
      appreciate. Grade 1 carcinomas make up about 45% of screening-detected breast
      carcinomas and about 20% of symptomatic breast cancers. The aim of this study was
      to evaluate the diagnostic sensitivity of grade 1 carcinomas and identify the
      critical features in the cytological diagnostic work-up of these tumours.
      METHODS: There were FNAC smears from 494 histologically confirmed grade 1
      carcinomas diagnosed during 1996-2004. The cytological diagnoses were compared
      with the histology. RESULTS: A definitive malignant diagnosis (absolute
      sensitivity) was given in 382 cases (77.3%). Equivocal or suspicious diagnoses
      were given in 75 (15.2%), benign or probably benign (false negative) in 24
      (4.8%). Thirteen cases (2.6%) were unsatisfactory. Complete sensitivity was
      92.7%. Invasive ductal carcinomas comprised 81.3% of all cases; absolute
      sensitivity for these was 80.9%. Invasive lobular and tubular carcinomas
      comprised 7.3% and 5.9% of cases, respectively; absolute sensitivity for these
      diagnosis was 50.0% and 57.1%, respectively, significantly lower than for other
      subtypes (P <or= 0.0001) whereas the difference for complete sensitivity was less
      but still significant (P = 0.017). Absolute and complete sensitivities were lower
      for tumours less than 1 cm size compared with more than 1 cm (P <or= 0.00001).
      CONCLUSION: Preoperative FNAC diagnosis of grade 1 breast carcinoma has a high
      sensitivity, especially in ductal carcinomas. Invasive lobular and tubular
      carcinomas were less likely to receive a definite preoperative diagnosis. The
      main reason for not reaching a definitive malignant diagnosis was sampling error
      due to small tumours less than 1 cm in diameter, irrespective of tumour subtype.

PMID- 18627407
TI  - The subcutaneous brow- and forehead-lift: a face-lift for the forehead and brow.
AB  - PURPOSE: The purpose is to present a less invasive and technically simpler method
      for brow and forehead rejuvenation and literature review on the subject.
      MATERIALS AND METHODS: Fifty consecutive female patients were treated with the
      subcutaneous brow-lift technique over a 30-month period by the same surgeon. This
      surgical technique is performed under direct vision utilizing an extreme beveled
      incision made 4 to 5 mm into the anterior hairline with subcutaneous dissection
      of the anterior forehead only with the excision of 1.5 to 2.0 cm of excess skin.
      RESULTS: This technique provided stable brow and forehead rejuvenation without
      hairline elevation. All patients were pleased with the result. No patients
      complained of problematic scars, permanent dysesthesia, or need to alter their
      hair style. Patients that were treated with simultaneous blepharoplasty were,
      overall, more pleased with the procedure. CONCLUSION: This technique has proven
      to be a viable alternative to endoscopic and other modes of brow- and forehead
      lifting in the author's practice. When compared to contemporary endoscopic
      techniques, this procedure does not require specialized equipment, is performed
      under direct vision, does not elevate the hairline, and has a more dramatic
      effect on forehead rhytides. The incision design allows hair regrowth through the
      scar making it extremely aesthetic and hidden.

PMID- 18627408
TI  - Soil microbial respiration in arctic soil does not acclimate to temperature.
AB  - Warming-induced release of CO2 from the large carbon (C) stores in arctic soils
      could accelerate climate change. However, declines in the response of soil
      respiration to warming in long-term experiments suggest that microbial activity
      acclimates to temperature, greatly reducing the potential for enhanced C losses.
      As reduced respiration rates with time could be equally caused by substrate
      depletion, evidence for thermal acclimation remains controversial. To overcome
      this problem, we carried out a cooling experiment with soils from arctic Sweden.
      If acclimation causes the reduction in soil respiration observed after
      experimental warming, then it should subsequently lead to an increase in
      respiration rates after cooling. We demonstrate that thermal acclimation did not
      occur following cooling. Rather, during the 90 days after cooling, a further
      reduction in the soil respiration rate was observed, which was only reversed by
      extended re-exposure to warmer temperatures. We conclude that over the time scale
      of a few weeks to months, warming-induced changes in the microbial community in
      arctic soils will amplify the instantaneous increase in the rates of CO2
      production and thus enhance C losses potentially accelerating the rate of 21st
      century climate change.

PMID- 18627409
TI  - Effects of experimental inbreeding on herbivore resistance and plant fitness: the
      role of history of inbreeding, herbivory and abiotic factors.
AB  - Inbreeding is common in plant populations and can affect plant fitness and
      resistance against herbivores. These effects are likely to depend on population
      history. In a greenhouse experiment with plants from 17 populations of Lychnis
      flos-cuculi, we studied the effects of experimental inbreeding on resistance and
      plant fitness. Depending on the levels of past herbivory and abiotic factors at
      the site of plant origin, we found either inbreeding or outbreeding depression in
      herbivore resistance. Furthermore, when not damaged experimentally by snail
      herbivores, plants from populations with higher heterozygosity suffered from
      inbreeding depression and those from populations with lower heterozygosity
      suffered from outbreeding depression. These effects of inbreeding and outbreeding
      were not apparent under experimental snail herbivory. We conclude that inbreeding
      effects on resistance and plant fitness depend on population history. Moreover,
      herbivory can mask inbreeding effects on plant fitness. Thus, understanding
      inbreeding effects on plant fitness requires studying multiple populations and
      considering population history and biotic interactions.

PMID- 18627410
TI  - Plant species traits are the predominant control on litter decomposition rates
      within biomes worldwide.
AB  - Worldwide decomposition rates depend both on climate and the legacy of plant
      functional traits as litter quality. To quantify the degree to which functional
      differentiation among species affects their litter decomposition rates, we
      brought together leaf trait and litter mass loss data for 818 species from 66
      decomposition experiments on six continents. We show that: (i) the magnitude of
      species-driven differences is much larger than previously thought and greater
      than climate-driven variation; (ii) the decomposability of a species' litter is
      consistently correlated with that species' ecological strategy within different
      ecosystems globally, representing a new connection between whole plant carbon
      strategy and biogeochemical cycling. This connection between plant strategies and
      decomposability is crucial for both understanding vegetation-soil feedbacks, and
      for improving forecasts of the global carbon cycle.

PMID- 18627411
TI  - Enrichment of a dioxin-dehalogenating Dehalococcoides species in two-liquid phase
      cultures.
AB  - Enrichment cultures capable of reductively dechlorinating 1,2,4-trichlorodibenzo
      p-dioxin (1,2,4-TrCDD) were shown to dechlorinate 1,2,3-trichlorobenzene (1,2,3
      TrCB) to 1,3-dichlorobenzene. To test if this activity can be used to enrich for
      dioxin-dechlorinating bacteria, a two-liquid phase cultivation with 200 mM 1,2,3
      TrCB dissolved in hexadecane was established. During the dechlorination of 1,2,3
      TrCB, the number of 1,2,4-TrCDD-dechlorinating bacteria increased by four orders
      of magnitude, eventually accounting for 11% of the total cell number.
      Characterization of the bacterial communities of the initial dioxin
      dechlorinating culture and of the trichlorobenzene enrichments by restriction
      fragment length polymorphism (RFLP) analysis of cloned 16S rRNA genes revealed a
      proportional increase of nine different sequence types, one representing a
      Dehalococcoides strain. Inhibition of methanogens further enhanced the rate of
      chlorobenzene dehalogenation and also resulted in a rapid dechlorination of
      1,2,3,4-tetrachlorodibenzo-p-dioxin that was applied via a hexadecane phase. The
      further enrichment was monitored by terminal RFLP, quantitative real-time PCR and
      microscopy, and aimed at the reduction of the accompanying non-dehalogenating
      populations by using different combinations of electron donors and the
      application of antibiotics. Hydrogen as the sole electron donor proved to be less
      efficient due to the co-enrichment of acetogens. The novel Dehalococcoides strain
      DCMB5 was enriched up to 50% by the cultivation with organic acids, hydrogen and
      vancomycin, and was finally purified by conventional isolation techniques.

PMID- 18627412
TI  - Identity and abundance of active sulfate-reducing bacteria in deep tidal flat
      sediments determined by directed cultivation and CARD-FISH analysis.
AB  - The identity and abundance of potentially active sulfate-reducing bacteria (SRB)
      in several metre deep sediments of a tidal sand flat in the German Wadden Sea
      were assessed by directed cultivation and cultivation-independent CARD-FISH
      analysis (catalysed reporter deposition fluorescence in situ hybridization).
      Presumably abundant SRB from different sediment layers between 0.5 and 4 m depth
      were selectively enriched in up to million-fold diluted cultures supplemented
      with lactate, acetate or hydrogen. Partial 16S rRNA gene sequences obtained from
      highest dilution steps showing sulfide formation indicated growth of
      deltaproteobacterial SRB belonging to the Desulfobulbaceae and the
      Desulfobacteraceae as well as of members of the Firmicutes. Subsequent isolation
      resulted in 10 novel phylotypes of both litho- and organotrophic sulfate-reducing
      Deltaproteobacteria. Molecular pre-screening identified six isolates as members
      of the Desulfobulbaceae, sharing highest identities with either candidatus
      'Desulfobacterium corrodens' (95-97%) or Desulfobacterium catecholicum (98%), and
      four isolates as members of Desulfobacteraceae, being related to either
      Desulfobacter psychrotolerans (98%) or Desulfobacula phenolica (95-97%).
      Relatives of D. phenolica were exlusively isolated from 50 and 100 cm deep
      sediments with 10 and 2 mM of pore water sulfate respectively. In contrast,
      relatives of D. corrodens, D. psychrotolerans and D. catecholicum were also
      obtained from layers deeper than 100 cm and with less than 2 mM sulfate. The high
      in situ abundance of members of both families in sediment layers beneath 50 cm
      could be confirmed via CARD-FISH analysis performed with a set of six SRB
      specific oligonucleotide probes. Moreover, SRB represented a numerically
      significant fraction of the microbial community throughout the sediment (up to
      7%) and reached even higher cell numbers in deep, sulfate-poor layers than in the
      sulfate-rich surface sediment. This relatively large community size of
      potentially active SRB in deep sandy sediments might on the one hand be a result
      of their syntrophic association with other anaerobes. Our results furthermore
      support the hypothesis that enhanced advective pore water transport might supply
      nutrients to microbial communities in deep sandy sediments and point to their so
      far unrecognized contribution to biogeochemical processes in Wadden Sea
      sediments.

PMID- 18627413
TI  - Comparative analysis of genome fragments of Acidobacteria from deep Mediterranean
      plankton.
AB  - Acidobacteria constitute a still poorly studied phylum that is well represented
      in soils. Recent studies suggest that members of this phylum may be also abundant
      in deep-sea plankton, but their relative abundance and ecological role in this
      ecosystem are completely unknown. A recent screening of three metagenomic deep
      sea libraries of bathypelagic plankton from the South Atlantic (1000 m depth),
      the Adriatic (1000 m depth) and the Ionian (3000 m depth) seas in the
      Mediterranean revealed an unexpected relative proportion of acidobacterial
      fosmids, which affiliated to the Solibacterales (Group 3), to the Group 11 and,
      most frequently, to the Group 6 of this diverse phylum. Here, we present the
      comparative analysis of 11 acidobacterial genome fragments containing the rrn
      operon from these Mediterranean libraries. A highly conserved syntenic region
      spanning up to 30 kb and containing up to 25 open reading frames was shared by
      Group 6 Acidobacteria. Synteny was also partially conserved in distantly related
      acidobacterial genome fragments derived from a metagenomic soil library,
      indicating a remarkable conservation of this genomic region within these
      Acidobacteria. A search for Acidobacteria-specific hits in directly comparable,
      available fosmid-end sequences from soil and marine metagenomic libraries showed
      a significant increase of their relative proportion in plankton libraries as a
      function of increasing depth reaching, at high depth, levels nearly comparable to
      those of soil. Thus, our results suggest that Acidobacteria are abundant and
      represent a significant proportion of the microbial community in the deep-sea
      ecosystem.

PMID- 18627414
TI  - The clinical impact of pharmacogenetics on the treatment of epilepsy.
AB  - Drug treatment of epilepsy is characterized by unpredictability of efficacy,
      adverse drug reactions, and optimal doses in individual patients, which, at least
      in part, is a consequence of genetic variation. Since genetic variability in drug
      metabolism was reported to affect the treatment with phenytoin more than 25 years
      ago, the ultimate goal of pharmacogenetics is to use the genetic makeup of an
      individual to predict drug response and efficacy, as well as potential adverse
      drug events. However, determining the practical relevance of pharmacogenetic
      variants remains difficult, in part because of problems with study design and
      replication. This article reviews the published work with particular emphasis on
      pharmacogenetic alterations that may affect efficacy, tolerability, and safety of
      antiepileptic drugs (AEDs), including variation in genes encoding drug target
      (SCN1A), drug transport (ABCB1), drug metabolizing (CYP2C9, CYP2C19), and human
      leucocyte antigen (HLA) proteins. Although the current studies associating
      particular genes and their variants with seizure control or adverse events have
      inherent weaknesses and have not provided unifying conclusions, several results,
      for example that Asian patients with a particular HLA allele, HLA-B*1502, are at
      a higher risk for Stevens-Johnson syndrome when using carbamazepine, are helpful
      to increase our knowledge how genetic variation affects the treatment of
      epilepsy. Although genetic testing raises ethical and social issues, a better
      understanding of the genetic influences on epilepsy outcome is key to developing
      the much needed new therapeutic strategies for individuals with epilepsy.

PMID- 18627415
TI  - Good surgical outcome in discordant ictal EEG-MRI unilateral mesial temporal
      sclerosis patients.
AB  - PURPOSE: Video electroencephalography (vEEG) monitoring of patients with
      unilateral mesial temporal sclerosis (uMTS) may show concordant or discordant
      seizure onset in relation to magnetic resonance imaging (MRI) evidence of MTS.
      Contralateral seizure usually leads to an indication of invasive monitoring.
      Contralateral seizure onset on invasive monitoring may contraindicate surgery. We
      evaluated long-term outcome after anteromesial temporal lobectomy (AMTL) in a
      consecutive series of uMTS patients with concordant and discordant vEEG findings,
      uniformly submitted to AMTL on the MRI evidence of MTS side without invasive
      monitoring. METHODS: We compared surgical outcome of all uMTS patients undergoing
      vEEG monitoring between January 1999 and April 2005 in our service. Discordant
      cases were defined by at least one seizure onset contralateral to the MRI
      evidence of MTS. Good surgical outcome was considered as Engel's class I. We also
      evaluated ictal SPECT concordance to ictal EEG and surgical outcome. RESULTS:
      Fifty-four patients had concordant (C) and 22 had discordant (D) scalp EEG and
      MRI. Surgical outcome was similar in both groups (C = 74% versus D = 86%).
      Duration of follow-up was comparable in both groups: C = 56.1 +/- 20.7 months
      versus D = 59.8 +/- 21.2 months (p = 0.83, nonsignificant). Discordant single
      photon emission computed tomography (SPECT) results did not influence surgical
      outcome. DISCUSSION: Surgical outcome was not influenced by contralateral vEEG
      seizure onset or contralateral increased flow on ictal SPECT. Although vEEG
      monitoring should still be performed in these patients, to rule out psychogenic
      seizures and extratemporal seizure onset, a potentially risky procedure such as
      invasive monitoring may not only not be indicated in this patient population, but
      may also lead to patients erroneously being denied surgery.

PMID- 18627416
TI  - Benefit of combination therapy in epilepsy: a review of the preclinical evidence
      with levetiracetam.
AB  - Levetiracetam (Keppra) is an antiepileptic drug (AED) characterized by a novel
      mechanism of action, unique profile of activity in seizure models, and broad
      spectrum clinical efficacy. The present report critically reviews several
      preclinical studies focused on combination therapy with levetiracetam and other
      anticonvulsants in various seizure and epilepsy models. Administration of
      levetiracetam together with many different clinically used AEDs or other
      anticonvulsants generally enhances their protective activity and, among existing
      AEDs, this was particularly prevalent with valproate. The protective activity of
      other AEDs was also enhanced by levetiracetam, which seems to be a universal
      finding that is independent of seizure model or drug combination studied.
      However, particularly strong enhancement was observed when levetiracetam was
      combined with agents either enhancing GABAergic or reducing glutamatergic
      neurotransmission. Importantly, these combinations were not associated with
      exacerbation of side effects or pharmacokinetic interactions. Based on the
      available preclinical data, it appears that combination treatment with
      levetiracetam and other anticonvulsants provides additional therapeutic benefit
      that may be attributed to its novel and distinct mechanism of action. Moreover,
      combinations of levetiracetam with clinically used AEDs that enhance GABAergic
      inhibition may be considered for rational polytherapy, which is often necessary
      in drug-resistant patients.

PMID- 18627417
TI  - Abnormal response of motor cortex to photic stimulation in idiopathic generalized
      epilepsy.
AB  - BACKGROUND: Intermittent photic stimulation (IPS) shortens the cortical silent
      period (CSP) elicited by transcranial magnetic stimulation (TMS) over the primary
      motor hand area (M1(HAND)). This response is absent in healthy individuals with a
      photoparoxysmal response (PPR). Here we combined TMS of the M1(HAND) with IPS to
      examine whether patients with idiopathic generalized epilepsy (IGE) exhibit an
      abnormal cortical response pattern to IPS. METHODS: In 13 PPR-positive and 12 PPR
      negative patients with IGE and in 13 PPR-negative healthy controls, we used focal
      TMS to the M1(HAND) to study how cortical excitability is changed by concurrent
      IPS at 50 Hz. RESULTS: IPS at 50 Hz reduced the duration of the CSP in healthy
      PPR-negative individuals, whereas IPS had no effect on the CSP in PPR-positive
      and PPR-negative patients with generalized epilepsy. The failure of IPS to
      shorten the CSP was independent of antiepileptic medication. Single-pulse or
      paired-pulse TMS only without concurrent IPS showed a higher motor threshold in
      PPR-positive patients with epilepsy, presumably caused by antiepileptic
      medication. No additional differences in cortical excitability were found among
      groups. CONCLUSIONS: Because the CSP is mediated by intracortical GABAergic
      mechanisms, our results indicate that IGEs are associated with an altered
      responsiveness of GABAergic inhibitory circuits in the M1(HAND). This
      electrophysiological trait is independent of photosensitivity. Excitability
      changes at the cortical or thalamic level may mediate this abnormal cortical
      response pattern in patients with IGE.

PMID- 18627419
TI  - Selective effects of CPAP on sleep apnoea-associated manifestations.
AB  - BACKGROUND: Visceral adiposity and obstructive sleep apnoea (OSA) may be
      independently associated with daytime sleepiness/low performance, insulin
      resistance, hypercytokinaemia, and/or hypertension. The objectives of this study
      are to simultaneously test these associations at baseline and after 3 months of
      continuous positive airway pressure (CPAP) therapy. MATERIALS AND METHODS:
      Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese
      controls were monitored in the sleep laboratory for four consecutive nights.
      Objective measures of daytime sleepiness and performance, serial 24 h plasma
      measures of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), TNF
      receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral
      adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using
      the same protocol after 3 months of CPAP. RESULTS: At baseline, IL-6, TNF-r1, and
      insulin resistance were highest in OSA patients, intermediate in obese controls,
      and lowest in non-obese controls (P < 0.05). Visceral fat was significantly
      greater in sleep apnoeics than obese controls and predicted insulin resistance
      and IL-6 levels, whereas OSA predicted TNF-r1 levels (P < 0.05). CPAP decreased
      daytime sleepiness and blood pressure (P < 0.05), but did not affect fasting
      glucose or insulin or around the clock adiponectin, IL-6, TNF-alpha, or TNF-r1
      levels. CONCLUSIONS: In obese sleep apnoeics, visceral fat is strongly associated
      with insulin resistance and inflammation. CPAP decreases sleepiness and moderates
      hypertension but does not affect visceral adiposity, insulin resistance,
      hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk
      factors for cardiovascular disease and diabetes.

PMID- 18627420
TI  - The establishment of an urban bird population.
AB  - 1. Despite the accelerating global spread of urbanized habitats and its
      associated implications for wildlife and humans, surprisingly little is known
      about the biology of urban ecosystems. 2. Using data from a 60-year study period,
      this paper provides a detailed description of how the northern goshawk Accipiter
      gentilis L.--generally considered a shy forest species--colonized the city of
      Hamburg, Germany. Six non-mutually exclusive hypotheses are investigated
      regarding the environmental factors that may have triggered this invasion. 3. The
      spatio-temporal analysis of 2556 goshawk chance observations (extracted from a
      total data set of 1 174 493 bird observations; 1946-2003) showed that hawks
      regularly visited the city centre decades before the first successful breeding
      attempts were recorded. Many observations were made in parts of the city where
      territories were established in later years, demonstrating that these early
      visitors had encountered, but not used, potential nest sites. 4. Pioneer
      settlement coincided with: (i) an increase in (legal) hunting pressure on
      goshawks in nearby rural areas; (ii) an increase in avian prey abundance in the
      city; and (iii) a succession of severe winters in the Greater Hamburg area. On
      the other hand, there was no evidence to suggest that the early stages of the
      invasion were due to: (i) decreasing food availability in rural areas; (ii) major
      habitat changes in the city; or (iii) rural intraguild dynamics forcing hawks
      into urban refugia. While breeding numbers of a potential rural source population
      were at a long-term low when the city was colonized, prior to first settlement
      there was a sharp increase of goshawk chance observations in the city and its
      rural periphery. 5. The urban population expanded rapidly, and pair numbers began
      to stabilize after about 10 years. Ringing data (219 ringed nestlings from 70
      urban broods; 1996-2000) demonstrated that most urban recruits had fledged in the
      city, but also confirmed considerable gene flow between urban and rural habitats.
      Analysis of chance observations (as raw data or as detrended time series)
      suggested a tight coupling of population dynamics inside and outside the city. 6.
      City-colonizations such as the one described here provide a valuable opportunity
      to study some fundamental aspects of population ecology on a scale at which
      detailed monitoring is logistically feasible. Furthermore, a good understanding
      of urban ecology has become essential for efficient wildlife conservation in
      modern, human-altered environments.

PMID- 18627418
TI  - Human herpes virus 6B: a possible role in epilepsy?
AB  - Human herpes virus 6 (HHV6) infection is nearly ubiquitous in childhood and may
      include central nervous system invasion. There are two variants, HHV6A and HHV6B.
      Usually asymptomatic, it is associated with the common, self-limited childhood
      illness roseola infantum and rarely with more severe syndromes. In patients with
      immune compromise, subsequent reactivation of viral activity may lead to severe
      limbic encephalitis. HHV6 has been identified as a possible etiologic agent in
      multiple sclerosis, myocarditis, and encephalitis. A preponderance of evidence
      supports an association between HHV6 and febrile seizures. An ongoing multicenter
      study is investigating possible links between HHV6 infection, febrile status
      epilepticus, and development of mesial temporal sclerosis (MTS). Investigation of
      temporal lobectomy specimens showed evidence of active HHV6B but not HHV6A
      replication in hippocampal astrocytes in about two-thirds of patients with MTS
      but not other causes of epilepsy. It has been suggested that HHV6B may cause
      "excitotoxicity" by interfering with astrocyte excitatory amino acid transport.
      Although conventional inflammatory changes are not found in most MTS specimens,
      inflammatory modulators may play a role in neuronal injury leading to MTS as
      well. If the link between early viral infection, complex or prolonged febrile
      seizures, and later development of intractable temporal lobe epilepsy is
      confirmed, new therapeutic approaches to a common intractable epilepsy syndrome
      may be possible.

PMID- 18627421
TI  - Osteopontin as two-sided mediator of intestinal inflammation.
AB  - Osteopontin (OPN) is characterized as a major amplifier of Th1-immune responses.
      However, its role in intestinal inflammation is currently unknown. We found
      considerably raised OPN levels in blood of wild-type (WT) mice with dextran
      sodium sulfate (DSS)-induced colitis. To identify the role of this mediator in
      intestinal inflammation, we analysed experimental colitis in OPN-deficient (OPN(
      /-)) mice. In the acute phase of colitis these mice showed more extensive colonic
      ulcerations and mucosal destruction than WT mice, which was abrogated by
      application of soluble OPN. Within the OPN(-/-) mice, infiltrating macrophages
      were not activated and showed impaired phagocytosis. Reduced mRNA expression of
      interleukin (IL)-1 beta and matrix metalloproteinases was found in acute colitis
      of OPN(-/-) mice. This was associated with decreased blood levels of IL-22, a
      Th17 cytokine that may mediate epithelial regeneration. However, OPN-(/-) mice
      showed increased serum levels of tumour necrosis factor (TNF)-alpha, which could
      be due to systemically present lipopolysaccharide translocated to the gut. In
      contrast to acute colitis, during chronic DSS-colitis, which is driven by a Th1
      response of the lamina propria infiltrates, OPN(-/-) mice were protected from
      mucosal inflammation and demonstrated lower serum levels of IL-12 than WT mice.
      Furthermore, neutralization of OPN in WT mice abrogated colitis. Lastly, we
      demonstrate that in patients with active Crohn's disease OPN serum concentration
      correlated significantly with disease activity. Taken together, we postulate a
      dual function of OPN in intestinal inflammation: During acute inflammation OPN
      seems to activate innate immunity, reduces tissue damage and initiates mucosal
      repair whereas during chronic inflammation it promotes the Th1 response and
      strengthens inflammation.

PMID- 18627423
TI  - The natural compound atraric acid is an antagonist  of the human androgen
      receptor inhibiting cellular  invasiveness and prostate cancer cell growth.
AB  - Extracts from Pygeum africanum are used in the treatment of prostatitis, benign
      prostatic hyperplasia and prostate cancer (Pca), major health problems of men in
      Western countries. The ligand-activated human androgen receptor (AR) supports the
      growth of the prostate gland. Inhibition of human AR by androgen ablation therapy
      and by applying synthetic anti-androgens is therefore the primary goal in
      treatment of patients. Here, we show that atraric acid (AA) isolated from bark
      material of Pygeum africanum has anti-androgenic activity, inhibiting the
      transactivation mediated by the ligand-activated human AR. This androgen
      antagonistic activity is receptor specific and does not inhibit the closely
      related glucocorticoid or progesterone receptors. Mechanistically, AA inhibits
      nuclear transport of AR. Importantly, AA is able to efficiently repress the
      growth of both the androgen-dependent LNCaP and also the androgen-independent C4
      2 Pca cells but not that of PC3 or CV1 cells lacking AR. In line with this, AA
      inhibits the expression of the endogenous prostate specific antigen gene in both
      LNCaP und C4-2 cells. Analyses of cell invasion revealed that AA inhibits the
      invasiveness of LNCaP cells through extracellular matrix. Thus, this study
      provides a molecular insight for AA as a natural anti-androgenic compound and may
      serve as a basis for AA derivatives as a new chemical lead structure for novel
      therapeutic compounds as AR antagonists, that can be used for prophylaxis or
      treatment of prostatic diseases.

PMID- 18627422
TI  - Pax genes in embryogenesis and oncogenesis.
AB  - The paired box genes are a family of nine developmental control genes, which in
      human beings (PAX) and mice (Pax) encode nuclear transcription factors. The
      temporal and spatial expressions of these highly conserved genes are tightly
      regulated during foetal development including organogenesis. PAX/Pax genes are
      switched off during the terminal differentiation of most structures. Specific
      mutations within a number of PAX/Pax genes lead to developmental abnormalities in
      both human beings and mice. Mutation in PAX3 causes Waardenburg syndrome, and
      craniofacial-deafness-hand syndrome. The Splotch phenotype in mouse exhibits
      defects in neural crest derivatives such as, pigment cells, sympathetic ganglia
      and cardiac neural crest-derived structures. The PAX family also plays key roles
      in several human malignancies. In particular, PAX3 is involved in
      rhabdomyosarcoma and tumours of neural crest origin, including melanoma and
      neuroblastoma. This review critically evaluates the roles of PAX/Pax in
      oncogenesis. It especially highlights recent advances in knowledge of how their
      genetic alterations directly interfere in the transcriptional networks that
      regulate cell differentiation, proliferation, migration and survival and may
      contribute to oncogenesis.

PMID- 18627424
TI  - Chitosan cooperates with mesenchyme-derived factors in regulating salivary gland
      epithelial morphogenesis.
AB  - Chitosan is a widely used biocompatible biomaterial in the tissue regeneration,
      but its utility and application in the tissue morphogenesis of salivary gland
      remains unclear. The study aimed to explore the effects of chitosan on the
      epithelial morphogenesis of submandibular gland (SMG). With chitosan, the
      branching morphogenesis of the whole SMG explant was facilitated, and the
      morphogenetic-promoting effects of mesenchymal tissue on SMG were further
      enhanced. Furthermore, chitosan was competent to induce recombined SMG epithelium
      to form branches in the serum-free condition independently. In the presence of
      chitosan, the morphogenetic efficacy of mesenchyme-derived growth factors
      responsible for epithelial morphogenesis including fibroblast growth factors 7,
      fibroblast growth factor 10 and hepatocyte growth factor increased. The specific
      epithelial phenotype induced by individual growth factor, which was required for
      the accomplishment of salivary epithelial morphogenesis, was promoted by
      chitosan. Moreover, the proliferative and the chemotactic properties of these
      growth factors towards the SMG epithelia were also reinforced by chitosan.
      Therefore, in orchestrating and intensifying the essential mesenchyme-derived
      growth factors, chitosan is versatile in mediating SMG epithelium to form a
      predetermined phenotype more efficiently and comprehensively. This study
      suggested that chitosan is a morphogenetic-regulating biomaterial for salivary
      tissue, which might be useful for the future salivary gland investigation and
      regeneration.

PMID- 18627427
TI  - The cleavage of thyroid-stimulating hormone receptor is  dependent on cell-cell
      contacts and regulates  the hormonal stimulation of phospholipase c.
AB  - Thyroid-stimulating hormone receptor (TSHR) consists of a hormone-binding
      extracellular subunit and a seven-transmembrane spanning subunit that interacts
      with the G proteins G(alphas) and G(alphaq). The two subunits, generated by
      proteolytic cleavage of a single polypeptide chain, are held together by
      disulphide bridges. The receptor is completely cleaved in thyroid tissue, while
      in cultured cells (thyrocytes and non-thyroid cells) the cleaved and uncleaved
      forms coexist. The reasons for these divergent data are not understood. Here we
      provide an explanation by showing that cleavage depends on cell-cell contacts. An
      almost complete cleavage was observed in confluent cells, while in sparse cells
      most of the receptor was in the uncleaved form. We also show that coupling of
      TSHR to G(alphaq) (as measured by inositolphosphate generation) is markedly
      reduced when the receptor is not cleaved. In contrast, coupling to G(alphas) [as
      measured by cyclic adenosine 3',5'-monophosphate (cAMP) synthesis] is unaffected
      by cleavage of the receptor. These results suggest that the cell-cell contacts
      are necessary for cleavage of the receptor, which acts as a regulatory step in
      inositolphosphate production via phospholipase C activation. The latter
      observation was confirmed using cells that express the uncleavable mutant TSHR
      delta50-NET, for which the TSH-stimulated inositolphosphate production was
      completely abolished.

PMID- 18627428
TI  - Clinicopathological features and prognosis of drug rash with eosinophilia and
      systemic symptoms: a study of 30 cases in Taiwan.
AB  - BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS), a group of
      non-blistering severe cutaneous adverse drug reactions (SCADRs), is characterized
      by skin rash and multiorgan involvement. Details of this reaction have not been
      reported in the literature so far. AIM: We investigate clinical and pathological
      features and prognosis of DRESS and hope this study will provide data concerning
      this disorder in Taiwan. METHODS: From January 2001 to June 2006, a total of 30
      patients, diagnosed with DRESS, were enrolled and evaluated for demographic
      characteristics, pathological findings, complications and outcome. RESULTS:
      Patient ages ranged from 13 to 78, with an equal sex ratio. The most common
      offending drug was allopurinol followed by carbamazepine. Pathologic changes
      observed were lichenoid dermatitis, erythema multiforme, pseudolymphoma and
      vasculitis. Impairment of liver and renal functions and blood dyscrasia were
      frequent complications. Active infection or reactivation of HHV-6 was observed in
      7 of 11 patients studied serologically. Two patients developed type 1 diabetes
      mellitus. The mortality rate was 10% (3 of 30). CONCLUSIONS: DRESS is a
      heterogeneous group of life-threatening conditions. The leading drug in DRESS in
      Taiwan is allopurinol. High eosinophil count and multiple underlying diseases are
      poor prognostic factors in patients with DRESS.

PMID- 18627429
TI  - T-cell-associated hypereosinophilic syndrome: case report and an appraisal of the
      new classification.

PMID- 18627430
TI  - Offering choices to people with intellectual disabilities: an interactional
      study.
AB  - BACKGROUND: At the level of policy recommendation, it is agreed that people with
      intellectual impairments ought to be given opportunities to make choices in their
      lives; indeed, in the UK, the Mental Capacity Act of 2005 enshrines such a right
      in law. However, at the level of practice, there is a dearth of evidence as to
      how choices are actually offered in everyday situations, which must hinder
      recommendations to change. METHOD: This qualitative interactional study, based on
      video recordings in British residential homes, combines ethnography with the fine
      grained methods of Conversation Analysis. RESULTS: We identify six conversational
      practices that staff use to offer choices to residents with intellectual
      disabilities. CONCLUSIONS: We describe the unwanted consequences of some of these
      practices, and how the institutional imperative to solicit clear and decisive
      choice may sometimes succeed only in producing the opposite.

PMID- 18627431
TI  - What clinical characteristics of children with autism influence their inclusion
      in regular classrooms?
AB  - BACKGROUND: This study took place in the context of recent legislation enacted in
      several countries--including France--and aimed at promoting inclusion of children
      with intellectual disabilities. It focuses on young children with autism and
      examines the links between the children's characteristics and their weekly hours
      of regular-classroom inclusion and intervention in specialised setting. METHOD:
      Standardised clinical and sociodemographic data were collected for 77 children
      with autism, along with data about their interventional programmes. RESULTS: The
      study showed that the number of hours of inclusion at school was influenced by
      the children's behavioural and adaptive characteristics, as well as by the
      socioprofessional category of their parents, although these factors did not
      affect the number of hours spent in specialised setting. Moreover, the total
      amount of time per week spent in interventional services of any kind was very
      small for some of the children. CONCLUSION: The time spent in special
      intervention services and regular classrooms combined did not add up to an
      adequate number of weekly hours for these children, particularly those exhibiting
      at least one of the following characteristics: low adaptation level, major
      behavioural problems or low socioprofessional category of parents.

PMID- 18627432
TI  - Inhibition of glutaminyl cyclase prevents pGlu-Abeta formation after
      intracortical/hippocampal microinjection in vivo/in situ.
AB  - Modified amyloid beta (Abeta) peptides represent major constituents of the
      amyloid deposits in Alzheimer's disease and Down's syndrome. In particular, N
      terminal pyroglutamate (pGlu) following truncation renders Abeta more stable,
      increases hydrophobicity and the aggregation velocity. Recent evidence based on
      in vitro studies suggests that the cyclization of glutamic acid, leading to pGlu
      Abeta, is catalyzed by the enzyme glutaminyl cyclase (QC) following limited
      proteolysis of Abeta at the N-terminus. Here, we studied the pGlu-formation by
      rat QC in vitro as well as after microinjection of Abeta(1-40) and Abeta(3-40)
      into the rat cortex in vivo/in situ with and without pharmacological QC
      inhibition. Significant pGlu-Abeta formation was observed following injection of
      Abeta(3-40) after 24 h, indicating a catalyzed process. The generation of pGlu
      Abeta from Abeta(3-40) was significantly inhibited by intracortical
      microinjection of a QC inhibitor. The study provides first evidence that
      generation of pGlu-Abeta is a QC-catalyzed process in vivo. The approach per se
      offers a strategy for a rapid evaluation of compounds targeting a reduction of
      pGlu formation at the N-terminus of amyloid peptides.

PMID- 18627433
TI  - PLC-dependent intracellular Ca2+ release was associated with C6-ceramide-induced
      inhibition of Na+ current in rat granule cells.
AB  - In this report, the effects of C(6)-ceramide on the voltage-gated inward Na(+)
      currents (I(Na)), two types of main K(+) current [outward rectifier delayed K(+)
      current (I(K)) and outward transient K(+) current (I(A))], and cell death in
      cultured rat cerebellar granule cells were investigated. At concentrations of
      0.01-100 microM, ceramide produced a dose-dependent and reversible inhibition of
      I(Na) without alteration of the steady-state activation and inactivation
      properties. Treatment with C(2)-ceramide caused a similar inhibitory effect on
      I(Na). However, dihydro-C(6)-ceramide failed to modulate I(Na). The effect of
      C(6)-ceramide on I(Na) was abolished by intracellular infusion of the Ca(2+)
      chelating agent, 1,2-bis (2-aminophenoxy) ethane-N, N, N9, N9-tetraacetic acid,
      but was mimicked by application of caffeine. Blocking the release of Ca(2+) from
      the sarcoplasmic reticulum with ryanodine receptor blocker induced a gradual
      increase in I(Na) amplitude and eliminated the effect of ceramide on I(Na). In
      contrast, the blocker of the inositol 1,4,5-trisphosphate-sensitive Ca(2+)
      receptor did not affect the action of C(6)-ceramide. Intracellular application of
      GTPgammaS also induced a gradual decrease in I(Na) amplitude, while GDPbetaS
      eliminated the effect of C(6)-ceramide on I(Na). Furthermore, the C(6)-ceramide
      effect on I(Na) was abolished after application of the phospholipase C (PLC)
      blockers and was greatly reduced by the calmodulin inhibitors. Fluorescence
      staining showed that C(6)-ceramide decreased cell viability and blocking I(Na) by
      tetrodotoxin did not mimic the effect of C(6)-ceramide, and inhibiting
      intracellular Ca(2+) release by dantrolene could not decrease the C(6)-ceramide
      induced cell death. We therefore suggest that increased PLC-dependent Ca(2+)
      release through the ryanodine-sensitive Ca(2+) receptor may be responsible for
      the C(6)-ceramide-induced inhibition of I(Na), which does not seem to be
      associated with C(6)-ceramide-induced granule neuron death.

PMID- 18627435
TI  - P2Y1 receptor-mediated glutamate release from cultured dorsal spinal cord
      astrocytes.
AB  - P2 receptors have been implicated in the release of neurotransmitter and
      proinflammatory cytokines by the response to neuroexcitatory substances in
      astrocytes. In the present study, we examined the mechanisms of ADP and adenosine
      5'-O-2-thiodiphosphate (ADPbetaS, ADP analogue) on glutamate release from
      cultured dorsal spinal cord astrocytes by using confocal laser scanning
      microscopy and HPLC. Immunofluorescence activity showed that P2Y(1) receptor
      protein is expressed in cultured astrocytes. ADP and ADPbetaS-induced [Ca(2+)](i)
      increase and glutamate release are mediated by P2Y(1) receptor. Ca(2+) release
      from IP(3)-sensitive calcium stores and protein kinase C (PKC) activation is
      important for glutamate release from astrocytes. Furthermore, P2Y(1) receptor
      evoked glutamate release is regulated by volume-sensitive Cl(-) channels and
      anion co-transporter, which open up the possibility that P2Y(1) receptor
      activation causes the increase of cell volume. Release of glutamate by ADPbetaS
      was abolished by 5-nitro-2 (3-phenyl propy lamino)-benzoate plus furosemide but
      was unaffected by botulinum toxin A. These observations indicate that P2Y(1)
      receptor-evoked glutamate may be mediated via volume-sensitive Cl(-) channel but
      not via exocytosis of glutamate containing vesicles. We speculate that P2Y(1)
      receptors-evoked glutamate efflux, occurring under pathological condition, may
      modulate the activity of synapses in spinal cord.

PMID- 18627434
TI  - Translation arrest and ribonomics in post-ischemic brain: layers and layers of
      players.
AB  - A persistent translation arrest (TA) correlates precisely with the selective
      vulnerability of post-ischemic neurons. Mechanisms of post-ischemic TA that have
      been assessed include ribosome biochemistry, the link between TA and stress
      responses, and the inactivation of translational components via sequestration in
      subcellular structures. Each of these approaches provides a perspective on post
      ischemic TA. Here, we develop the notion that mRNA regulation via RNA-binding
      proteins, or ribonomics, also contributes to post-ischemic TA. We describe the
      ribonomic network, or structures involved in mRNA regulation, including nuclear
      foci, polysomes, stress granules, embryonic lethal abnormal vision/Hu granules,
      processing bodies, exosomes, and RNA granules. Transcriptional, ribonomic, and
      ribosomal regulation together provide multiple layers mediating cell
      reprogramming. Stress gene induction via the heat-shock response, immediate early
      genes, and endoplasmic reticulum stress represents significant reprogramming of
      post-ischemic neurons. We present a model of post-ischemic TA in ischemia
      resistant neurons that incorporates ribonomic considerations. In this model,
      selective translation of stress-induced mRNAs contributes to translation
      recovery. This model provides a basis to study dysfunctional stress responses in
      vulnerable neurons, with a key focus on the inability of vulnerable neurons to
      selectively translate stress-induced mRNAs. We suggest a ribonomic approach will
      shed new light on the roles of mRNA regulation in persistent TA in vulnerable
      post-ischemic neurons.

PMID- 18627436
TI  - Expression of Kv1.2 in microglia and its putative roles in modulating production
      of proinflammatory cytokines and reactive oxygen species.
AB  - Microglial cells are endowed with different potassium ion channels but their
      expression and specific functions have remained to be fully clarified. This study
      has shown Kv1.2 expression in the amoeboid microglia in the rat brain between 1
      (P1) and 10 (P10) days of age. Kv1.2 expression was localized in the ramified
      microglia at P14 and was hardly detected at P21. In postnatal rats exposed to
      hypoxia, Kv1.2 immunoreactivity in microglia was markedly enhanced. Quantitative
      RT-PCR analysis confirmed Kv1.2 mRNA expression in microglial cells in vitro. It
      was further shown that Kv1.2 and protein expression coupled with that of
      interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) was
      significantly increased when the cells were subjected to hypoxia. The same
      increase was observed in cells exposed to adenosine 5'-triphosphate (ATP) and
      lipopolysaccharide (LPS). Concomitantly, the intracellular potassium
      concentration decreased significantly. Blockade of Kv1.2 channel with
      rTityustoxin-Kalpha (TsTx) resulted in partial recovery of intracellular
      potassium concentration accompanied by a reduced expression of IL-1beta and TNF
      alpha mRNA and protein expression and intracellular reactive oxygen species (ROS)
      production. We conclude that Kv1.2 in microglia modulates IL-1beta and TNF-alpha
      expression and ROS production probably by regulating the intracellular potassium
      concentration.

PMID- 18627437
TI  - Sweet taste receptor interacting protein CIB1 is a general inhibitor of InsP3
      dependent Ca2+ release in vivo.
AB  - In a search for sweet taste receptor interacting proteins, we have identified the
      calcium- and integrin-binding protein 1 (CIB1) as specific binding partner of the
      intracellular carboxyterminal domain of the rat sweet taste receptor subunit
      Tas1r2. In heterologous human embryonic kidney 293 (HEK293) cells, the G protein
      chimeras Galpha(16gust44) and Galpha(15i3) link the sweet taste receptor dimer
      TAS1R2/TAS1R3 to an inositol 1,4,5-trisphosphate (InsP3)-dependent Ca2+ release
      pathway. To demonstrate the influence of CIB1 on the cytosolic Ca2+
      concentration, we used sweet and umami compounds as well as other InsP3
      generating ligands in FURA-2-based Ca2+ assays in wild-type HEK293 cells and
      HEK293 cells expressing functional human sweet and umami taste receptor dimers.
      Stable and transient depletion of CIB1 by short-hairpin RNA increased the Ca2+
      response of HEK293 cells to the InsP3-generating ligands ATP, UTP and carbachol.
      Over-expression of CIB1 had the opposite effect as shown for the sweet ligand
      saccharin, the umami receptor ligand monosodium glutamate and UTP. The CIB1
      effect was dependent on the thapsigargin-sensitive Ca2+ store of the endoplasmic
      reticulum (ER) and independent of extracellular Ca2+. The function of CIB1 on
      InsP3-evoked Ca2+ release from the ER is most likely mediated by its interaction
      with the InsP3 receptor. Thus, CIB1 seems to be an inhibitor of InsP3-dependent
      Ca2+ release in vivo.

PMID- 18627438
TI  - A trend of increase in periodontal interleukin-6 expression across patients with
      neither diabetes nor periodontal disease, patients with periodontal disease
      alone, and patients with both diseases.
AB  - BACKGROUND AND OBJECTIVE: Epidemiological studies have established that patients
      with diabetes have increased prevalence and severity of periodontal disease.
      However, the periodontal expression of inflammatory cytokines and matrix
      metalloproteinases (MMPs) in diabetic patients has not been well characterized.
      The objective of this study was to determine the difference in the periodontal
      expression of MMP-1, MMP-8, interleukin-6, tumor necrosis factor-alpha and
      interleukin-1beta between diabetic and nondiabetic patients. MATERIAL AND
      METHODS: Periodontal tissue specimens were collected from nine nondiabetic
      patients without periodontal disease (group 1), from 11 nondiabetic patients with
      periodontal disease (group 2) and from seven diabetic patients with periodontal
      disease (group 3). The expression of MMP-1, MMP-8, interleukin-6, tumor necrosis
      factor-alpha and interleukin-1beta was quantified using real-time polymerase
      chain reaction. RESULTS: The nonparametric Kruskal-Wallis test showed that the
      difference in interleukin-6 expression among the groups was statistically
      significant (p = 0.04). Furthermore, the generalized Kruskal-Wallis nonparametric
      linear-by-linear association test showed a statistically significant trend of
      increase in the expression of interleukin-6 from group 1 to group 2 to group 3 (p
      = 0.02) and a suggestion of such a trend for MMP-1 (p = 0.05). No increase in MMP
      8 expression was observed in patients in group 3 compared to patients in groups 1
      and 2. Although the average expression levels of MMP-1, interleukin-1beta and
      tumor necrosis factor-alpha were increased from group 1 to group 3, the
      differences were not statistically significant. CONCLUSION: A trend of increased
      interleukin-6 expression in periodontal tissues was observed across patients with
      neither diabetes nor periodontal disease, patients with periodontal disease
      alone, and patients with both diseases.

PMID- 18627440
TI  - Dosing anticoagulant therapy with coumarin drugs: is genotyping clinically
      useful? Yes.

PMID- 18627441
TI  - Dosing anticoagulant therapy with coumarin drugs: is genotyping clinically
      useful? No.

PMID- 18627442
TI  - Contribution of indirect computed tomographic venography to the diagnosis of
      postpartum venous thromboembolism.
AB  - BACKGROUND: The diagnostic value of indirect computed tomographic venography
      (CTV), following thoracic computed tomographic angiography (CTA), has not been
      specifically evaluated in postpartum patients with suspected pulmonary embolism.
      OBJECTIVES: To assess the diagnostic value of CTV in postpartum venous
      thromboembolism. METHODS: We reviewed all CTA and CTV procedures performed during
      the last 7 years in our institution for suspected pulmonary embolism during the
      postpartum period. We focused on the quality of CTA, the rates of positive CTA
      and isolated positive CTV findings, and alternative diagnoses provided by CTV.
      RESULTS: Fifty-five CTA and 33 CTV procedures were performed for suspected
      pulmonary embolism in 47 patients referred between 24 h and 2 months after
      Cesarean (34 patients) or vaginal (13 patients) delivery. Of the 33 patients who
      had both CTA and CTV, seven had positive CTA findings and four had isolated
      positive CTV findings. Thus, the absolute increase in the venous thromboembolism
      detection rate following CTV was 12.1% [95% confidence interval (CI) 4.0-29.1].
      Subcapsular hematoma of the liver or spleen was found on CTV in another two
      patients without venous thromboembolism. Consequently, CTV had a direct impact on
      clinical management in six of 33 patients (18%). CONCLUSION: Our results suggest
      that postpartum patients with suspected pulmonary embolism have a significant
      rate of pelvic vein thrombosis and that the use of CTV leads to a 31% relative
      increase in the detection rate of venous thromboembolism as compared to CTA alone
      in these patients.

PMID- 18627443
TI  - Incidence of symptomatic venous thromboembolism following hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: The incidence of symptomatic venous thromboembolism (VTE) following
      hematopoietic stem cell transplantation (HSCT) is not well described,
      particularly with increased use of ambulatory care in the transplant setting.
      METHODS: A retrospective analysis involving 589 patients (382 autologous HSCT,
      207 allogeneic HSCT) undergoing transplantation between 2000 and 2005 in a single
      Canadian institution was undertaken to identify the incidence of proximal deep
      vein thrombosis (DVT) or pulmonary embolism (PE) in HSCT patients. RESULTS: The
      total 1-year incidence of symptomatic VTE was 3.7% [95% confidence interval (CI)
      2.5-5.6]. Among the HSCT patients, 7/589 (1.2%, 95% CI 0.6-2.4) developed
      symptomatic non-catheter-related VTE following HSCT (four PE and three DVT). All
      VTE events occurred after hematopoietic engraftment. Patients undergoing
      autologous HSCT did not receive thromboprophylaxis, whereas most patients
      undergoing allogeneic HSCT (79.7%) received enoxaparin 20 mg daily for the
      prevention of veno-occlusive disease of the liver, starting 6 +/- 3 days before
      transplantation for a mean of 22 +/- 14 days. CONCLUSION: HSCT patients have a
      high incidence of VTE. Thromboprophylaxis should potentially be considered in
      these patients. However, future studies assessing the risk and benefits of
      thromboprophylaxis are needed in this specific population.

PMID- 18627444
TI  - Pharmacokinetics and pharmacodynamics of a new highly secured fibrinogen
      concentrate.
AB  - BACKGROUND: Inherited afibrinogenemia is a rare autosomal recessive disorder
      characterized by the absence or trace amounts of plasma fibrinogen inducing
      varying bleeding tendencies. Little is known about the pharmacokinetics of plasma
      derived fibrinogen concentrates used in the treatment of afibrinogenemic
      patients. OBJECTIVE: This open, prospective, multicenter study assessed the
      pharmacokinetic and pharmacodynamic profiles of FIBRINOGENE T1 (FGT1; LFB, Les
      Ulis, France), a human fibrinogen concentrate treated with three specific
      biological safety steps. PATIENTS/METHODS: Five adult patients with congenital
      afibrinogenemia received a single infusion of 0.06 g kg(-1) of FGT1. Plasma
      samples drawn up to day 14 were assayed for fibrinogen antigen and activity and
      for coagulation parameters in a central laboratory. RESULTS: Fibrinogen antigen
      and activity were similar and highly correlated, with very low between-patient
      variability for pharmacokinetic parameters. Fibrinogen levels increased rapidly
      and significantly, with a mean plasma concentration of 1.39 g L(-1) being
      achieved 1 h after the end of the infusion, leading to almost complete in vivo
      recovery (94%). The mean half-life was 3.4 days, with slow linear elimination,
      and the distribution was mainly restricted to the vascular compartment.
      Coagulation parameters were normalized after the infusion and during the
      following 6-10 days. FGT1 was well tolerated overall. CONCLUSIONS: FGT1 behaves
      like natural functional fibrinogen, and its pharmacokinetic properties are in
      line with those expected from a fibrinogen concentrate. Our findings suggest that
      FGT1 can restore efficient hemostasis in afibrinogenemic patients, and predict
      good clinical efficacy.

PMID- 18627445
TI  - Lessons learned about integrating a medical school curriculum: perceptions of
      students, faculty and curriculum leaders.
AB  - OBJECTIVE: Recent educational reform in US medical schools has created integrated
      curricular structures. This study investigated how stakeholders in a newly
      integrated curriculum - students, course directors and curriculum leaders -
      define integration and perceive its successes and challenges during its first
      year. METHODS: We conducted interviews with curriculum reform leaders, course
      directors and first year medical students. Interview transcripts were analysed
      for themes, which were compared within and across stakeholder groups. RESULTS:
      Three curriculum leaders, four Year 1 course directors and six Year 1 medical
      students were interviewed. Fifteen students participated in a group interview.
      Four major themes emerged: interdisciplinary teaching; interdisciplinary faculty
      collaboration; building curricular links, and sequencing and framing curricular
      content. Cross-group analysis revealed participant agreement that an integrated
      curriculum required interdisciplinary teaching, clinical application and careful
      oversight. Differences among groups were also identified. Faculty (course
      directors and curriculum leaders) discussed faculty collaboration and the
      challenges of faculty buy-in and course implementation. Students highlighted the
      impact of integration on their learning and the challenges of sequencing and
      scaffolding content. Both students and course directors focused on course
      monitoring and conceptual links for student learning. CONCLUSIONS: Integrating a
      curriculum is a complex process. It is differentially understood and experienced
      by students and faculty, and can refer to instructional method, content, faculty
      work or synthesis of knowledge in the minds of learners. It can occur at
      different rates and some subjects are integrated more easily than others. We
      point to some specific considerations as medical schools embark on curriculum
      reform.

PMID- 18627447
TI  - Twenty years of phylogeography: the state of the field and  the challenges for
      the Southern Hemisphere.
AB  - Phylogeography is a young, vigorous and integrative field of study that uses
      genetic data to understand the history of populations. This field has recently
      expanded into many areas of biology and also into several historical disciplines
      of Earth sciences. In this review, I present a numerical synthesis of the
      phylogeography literature based on an examination of over 3000 articles published
      during the first 20 years of the field (i.e. from 1987 to 2006). Information from
      several topics needed to evaluate the progress, tendencies and deficiencies of
      the field is summarized for 10 major groups of organisms and at a global scale.
      The topics include the geography of phylogeographic surveys, comparative nature
      of studies, temporal scales and major environments investigated, and genetic
      markers used. I also identify disparities in research productivity between the
      developing and the developed world, and propose ways to reduce some of the
      challenges faced by phylogeographers from less affluent countries. Phylogeography
      has experienced explosive growth in recent years fuelled by developments in DNA
      technology, theory and statistical analysis. I argue that the intellectual
      maturation of the field will eventually depend not only on these recent
      developments, but also on syntheses of comparative information across different
      regions of the globe. For this to become a reality, many empirical
      phylogeographic surveys in regions of the Southern Hemisphere (and in developing
      countries of the Northern Hemisphere) are needed. I expect the information and
      views presented here will assist in promoting international collaborative work in
      phylogeography and in guiding research efforts at both regional and global
      levels.

PMID- 18627452
TI  - Fungal specificity bottlenecks during orchid germination and development.
AB  - Fungus-subsidized growth through the seedling stage is the most critical feature
      of the life history for the thousands of mycorrhizal plant species that propagate
      by means of 'dust seeds.' We investigated the extent of specificity towards fungi
      shown by orchids in the genera Cephalanthera and Epipactis at three stages of
      their life cycle: (i) initiation of germination, (ii) during seedling
      development, and (iii) in the mature photosynthetic plant. It is known that in
      the mature phase, plants of these genera can be mycorrhizal with a number of
      fungi that are simultaneously ectomycorrhizal with the roots of neighbouring
      forest trees. The extent to which earlier developmental stages use the same or a
      distinctive suite of fungi was unclear. To address this question, a total of 1500
      packets containing orchid seeds were buried for up to 3 years in diverse European
      forest sites which either supported or lacked populations of helleborine orchids.
      After harvest, the fungi associated with the three developmental stages, and with
      tree roots, were identified via cultivation-independent molecular methods. While
      our results show that most fungal symbionts are ectomycorrhizal, differences were
      observed between orchids in the representation of fungi at the three life stages.
      In Cephalanthera damasonium and C. longifolia, the fungi detected in seedlings
      were only a subset of the wider range seen in germinating seeds and mature
      plants. In Epipactis atrorubens, the fungi detected were similar at all three
      life stages, but different fungal lineages produced a difference in seedling
      germination performance. Our results demonstrate that there can be a narrow
      checkpoint for mycorrhizal range during seedling growth relative to the more
      promiscuous germination and mature stages of these plants' life cycle.

PMID- 18627454
TI  - A population genomic approach to map recent positive selection in model species.
AB  - Based on nearly complete genome sequences from a variety of organisms data on
      naturally occurring genetic variation on the scale of hundreds of loci to entire
      genomes have been collected in recent years. In parallel, new statistical tests
      have been developed to infer evidence of recent positive selection from these
      data and to localize the target regions of selection in the genome. These methods
      have now been successfully applied to Drosophila melanogaster, humans, mice and a
      few plant species. In genomic regions of normal recombination rates, the targets
      of positive selection have been mapped down to the level of individual genes.

PMID- 18627455
TI  - Evidence for multiple sources of invasion and intraspecific hybridization in
      Brachypodium sylvaticum (Hudson) Beauv. in North America.
AB  - We compared the levels and distribution of genetic diversity in Eurasian and
      North American populations of Brachypodium sylvaticum (Huds.) Beauv. (false
      brome), a newly invasive perennial bunchgrass in western North America. Our goals
      were to identify source regions for invasive populations, determine the number of
      independent invasion events, and assess the possibility that postinvasion
      bottlenecks and hybridization have affected patterns of genetic diversity in the
      invaded range. We tested the hypothesis that this Eurasian grass was accidentally
      introduced into two areas in Oregon and one site in California by examining
      nuclear microsatellites and chloroplast haplotype variation in 23 introduced and
      25 native populations. In the invaded range, there was significantly lower
      allelic richness (R(S)), observed heterozygosity (H(O)) and within-population
      gene diversity (H(S)), although a formal test failed to detect a significant
      genetic bottleneck. Most of the genetic variation existed among populations in
      the native range but within populations in the invaded range. All of the allelic
      variation in the invaded range could be explained based on alleles found in
      western European populations. The distribution of identified genetic clusters in
      the North American populations and the unique alleles associated with them is
      consistent with two historical introductions in Oregon and a separate
      introduction to California. Further analyses of population structure indicate
      that intraspecific hybridization among genotypes from geographically distinct
      regions of western Europe occurred following colonization in Oregon. The
      California populations, however, are more likely to be derived from one or
      perhaps several genetically similar regions in the native range. The emergence
      and spread of novel recombinant genotypes may be facilitating the rapid spread of
      this invasive species in Oregon.

PMID- 18627457
TI  - Pheromone-regulated target genes respond differentially to MAPK phosphorylation
      of transcription factor Prf1.
AB  - Pheromone signalling during mating is essential for pathogenicity of Ustilago
      maydis. The activity of the key transcription factor Prf1 is controlled at the
      transcriptional level and post-translationally by mitogen-activated protein
      kinase (MAPK) and protein kinase A (PKA) phosphorylation. However, the precise
      contribution of these regulatory mechanisms to the transcriptional output is
      unknown. Here, we genetically dissected the three levels of Prf1 regulation. We
      performed transcriptional profiling of respective mutants to identify and
      classify targets. This approach revealed that transcriptional regulation of prf1
      had only minor influence on target gene expression stressing the importance of
      post-translational control. PKA regulation of Prf1 was sufficient to control
      expression of nine pheromone-responsive genes including the major transcription
      factor regulating pathogenicity. MAPK regulation was necessary for the pheromone
      response of a set of 57 genes. In 35 cases, pheromone responsiveness was
      completely lost, while in the remaining 22 cases regulation was alleviated. This
      indicated a novel level of complexity in MAPK signalling suggesting that target
      genes respond differentially to MAPK phosphorylation of the respective
      transcription factors.

PMID- 18627458
TI  - Carbon metabolism of Listeria monocytogenes growing inside macrophages.
AB  - The intracellular metabolism of Listeria monocytogenes was studied by (13)C
      isotopologue profiling using murine J774A.1 macrophages as host cells. Six hours
      after infection, bacteria were separated from the macrophages and hydrolyzed.
      Amino acids were converted into tert-butyl-dimethylsilyl derivatives and
      subjected to gas chromatography/mass spectrometry. When the macrophages were
      supplied with [U-(13)C(6)]glucose prior to infection, but not during infection,
      label was detected only in Ala, Asp and Glu of the macrophage and bacterial
      protein with equal isotope distribution. When [U-(13)C(6)]glucose was provided
      during the infection period, (13)C label was found again in Ala, Asp and Glu from
      host and bacterial protein, but also in Ser, Gly, Thr and Val from the bacterial
      fraction. Mutants of L. monocytogenes defective in the uptake and catabolism of
      the C(3)-metabolites, glycerol and/or dihydroxyacetone, showed reduced
      incorporation of [U-(13)C(6)]glucose into bacterial amino acids under the same
      experimental settings. The (13)C pattern suggests that (i) significant fractions
      (50-100%) of bacterial amino acids were provided by the host cell, (ii) a C(3)
      metabolite can serve as carbon source for L. monocytogenes under intracellular
      conditions and (iii) bacterial biosynthesis of Asp, Thr and Glu proceeds via
      oxaloacetate by carboxylation of pyruvate.

PMID- 18627459
TI  - Specific residues in the N-terminal domain of FimH stimulate type 1 fimbriae
      assembly in Escherichia coli following the initial binding of the adhesin to FimD
      usher.
AB  - Type 1 fimbriae are assembled by the chaperone-usher pathway where periplasmic
      protein complexes formed between fimbrial subunits and the FimC chaperone are
      recruited by the outer membrane protein FimD (the usher) for their ordered
      polymerization and export. FimH adhesin initiates and stimulates type 1 fimbriae
      polymerization by interacting with FimD. Previously we showed that the N-terminal
      lectin domain of FimH (N-FimH) is necessary for binding of the adhesin to FimD.
      In this work, we have selected mutants in N-FimH that reduce the levels of
      adhesin and type 1 fimbriae displayed in Escherichia coli without altering the
      levels of FimH in the periplasm. The selected mutations are mostly concentrated
      in residues G15, N46 and D47. In contrast to other mutations isolated that simply
      affect binding of FimH to FimD (e.g. C3Y), these variants associate to FimD and
      alter its susceptibility to trypsin digestion similarly to wild-type FimH.
      Importantly, their mutant phenotype is rescued when FimD is activated in vivo by
      the coexpression of wild-type FimH. Altogether, these data indicate that residues
      G15, N46 and D47 play an important role following initial binding of FimH to FimD
      for efficient type 1 fimbriae polymerization by this outer membrane usher.

PMID- 18627460
TI  - Biosynthesis of mycobacterial arabinogalactan: identification of a novel alpha(1-
      >3) arabinofuranosyltransferase.
AB  - The cell wall mycolyl-arabinogalactan-peptidoglycan complex is essential in
      mycobacterial species, such as Mycobacterium tuberculosis and is the target of
      several antitubercular drugs. For instance, ethambutol targets arabinogalactan
      biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and
      Mt-EmbB. A bioinformatics approach identified putative integral membrane
      proteins, MSMEG2785 in Mycobacterium smegmatis, Rv2673 in Mycobacterium
      tuberculosis and NCgl1822 in Corynebacterium glutamicum, with 10 predicted
      transmembrane domains and a glycosyltransferase motif (DDX), features that are
      common to the GT-C superfamily of glycosyltransferases. Deletion of M. smegmatis
      MSMEG2785 resulted in altered growth and glycosyl linkage analysis revealed the
      absence of AG alpha(1-->3)-linked arabinofuranosyl (Araf) residues.
      Complementation of the M. smegmatis deletion mutant was fully restored to a wild
      type phenotype by MSMEG2785 and Rv2673, and as a result, we have now termed this
      previously uncharacterized open reading frame, arabinofuranosyltransferase C
      (aftC). Enzyme assays using the sugar donor beta-d-arabinofuranosyl-1
      monophosphoryl-decaprenol (DPA) and a newly synthesized linear alpha(1-->5)
      linked Ara(5) neoglycolipid acceptor together with chemical identification of
      products formed, clearly identified AftC as a branching alpha(1-->3)
      arabinofuranosyltransferase. This newly discovered glycosyltransferase sheds
      further light on the complexities of Mycobacterium cell wall biosynthesis, such
      as in M. tuberculosis and related species and represents a potential new drug
      target.

PMID- 18627461
TI  - Mating type influences chromosome loss and replicative senescence in telomerase
      deficient budding yeast by Dnl4-dependent telomere fusion.
AB  - As we age, the majority of our cells gradually lose the capacity to divide
      because of replicative senescence that results from the inability to replicate
      the ends of chromosomes. The timing of senescence is dependent on the length of
      telomeric DNA, which elicits a checkpoint signal when critically short.
      Critically short telomeres also become vulnerable to deleterious rearrangements,
      end-degradation and telomere-telomere fusions. Here we report a novel role of non
      homologous end-joining (NHEJ), a pathway of double-strand break repair in
      influencing both the kinetics of replicative senescence and the rate of
      chromosome loss in telomerase-deficient Saccharomyces cerevisiae. In telomerase
      deficient cells, the absence of NHEJ delays replicative senescence, decreases
      loss of viability during senescence, and suppresses senescence-associated
      chromosome loss and telomere-telomere fusion. Differences in mating-type gene
      expression in haploid and diploid cells affect NHEJ function, resulting in
      distinct kinetics of replicative senescence. These results suggest that the
      differences in the kinetics of replicative senescence in haploid and diploid
      telomerase-deficient yeast are determined by changes in NHEJ-dependent telomere
      fusion, perhaps through the initiation of the breakage-fusion-bridge cycle.

PMID- 18627462
TI  - A versatile partner of eukaryotic protein complexes that is involved in multiple
      biological processes: Kti11/Dph3.
AB  - The Kluyveromyces lactis killer toxin zymocin insensitive 11 (KTI11) gene from
      Saccharomyces cerevisiae is allelic with the diphthamide synthesis 3 (DPH3)
      locus. Here, we present evidence that the KTI11 gene product is a versatile
      partner of proteins and operates in multiple biological processes. Notably, Kti11
      immune precipitates contain Elp2 and Elp5, two subunits of the Elongator complex
      which is involved in transcription, tRNA modification and zymocin toxicity. KTI11
      deletion phenocopies Elongator-minus cells and causes antisuppression of nonsense
      and missense suppressor tRNAs (SUP4, SOE1), zymocin resistance and protection
      against the tRNase attack of zymocin. In addition and unlike Elongator mutants,
      kti11 mutants resist diphtheria toxin (DT), protect against ADP-ribosylation of
      eukaryotic translation elongation factor 2 (eEF2) by DT and induce resistance
      against sordarin, an eEF2 poisoning antifungal. The latter phenotype applies to
      all diphthamide mutants (dph1-dph5) tested and Kti11/Dph3 physically interacts
      with diphthamide synthesis factors Dph1 and Dph2, presumably as part of a
      trimeric complex. Moreover, we present a separation of function mutation in
      KTI11, kti11-1, which dissociates zymocin resistance from DT sensitivity. It
      encodes a C-terminal Kti11 truncation that almost entirely abolishes Elongator
      interaction without affecting association with Kti13, another Kti11 partner
      protein.

PMID- 18627463
TI  - The ylo-1 gene encodes an aldehyde dehydrogenase responsible for the last
      reaction in the Neurospora carotenoid pathway.
AB  - The accumulation of the apocarotenoid neurosporaxanthin and its carotene
      precursors explains the orange pigmentation of the Neurospora surface cultures.
      Neurosporaxanthin biosynthesis requires the activity of the albino gene products
      (AL-1, AL-2 and AL-3), which yield the precursor torulene. Recently, we
      identified the carotenoid oxygenase CAO-2, which cleaves torulene to produce the
      aldehyde beta-apo-4'-carotenal. This revealed a last missing step in Neurospora
      carotenogenesis, namely the oxidation of the CAO-2 product to the corresponding
      acid neurosporaxanthin. The mutant ylo-1, which exhibits a yellow colour, lacks
      neurosporaxanthin and accumulates several carotenes, but its biochemical basis is
      unknown. Based on available genetic data, we identified ylo-1 in the Neurospora
      genome, which encodes an enzyme representing a novel subfamily of aldehyde
      dehydrogenases, and demonstrated that it is responsible for the yellow phenotype,
      by sequencing and complementation of mutant alleles. In contrast to the precedent
      structural genes in the carotenoid pathway, light does not induce the synthesis
      of ylo-1 mRNA. In vitro incubation of purified YLO-1 protein with beta-apo-4'
      carotenal produced neurosporaxanthin through the oxidation of the terminal
      aldehyde into a carboxyl group. We conclude that YLO-1 completes the set of
      enzymes needed for the synthesis of this major Neurospora pigment.

PMID- 18627464
TI  - Identification and characterization of two trypanosome TFIIS proteins exhibiting
      particular domain architectures and differential nuclear localizations.
AB  - Nuclear transcription of Trypanosoma brucei displays unusual features. Most
      protein-coding genes are organized in large directional gene clusters, which are
      transcribed polycistronically by RNA polymerase II (pol II) with subsequent
      processing to generate mature mRNA. Here, we describe the identification and
      characterization of two trypanosome homologues of transcription elongation factor
      TFIIS (TbTFIIS1 and TbTFIIS2-1). TFIIS has been shown to aid transcription
      elongation by relieving arrested pol II. Our phylogenetic analysis demonstrated
      the existence of four independent TFIIS expansions across eukaryotes. While
      TbTFIIS1 contains only the canonical domains II and III, the N-terminus of
      TbTFIIS2-1 contains a PWWP domain and a domain I. TbTFIIS1 and TbTFIIS2-1 are
      expressed in procyclic and bloodstream form cells and localize to the nucleus in
      similar, but distinct, punctate patterns throughout the cell cycle. Neither TFIIS
      protein was enriched in the major pol II sites of spliced-leader RNA
      transcription. Single RNA interference (RNAi)-mediated knock-down and knockout
      showed that neither protein is essential. Double knock-down, however, impaired
      growth. Repetitive failure to generate a double knockout of TbTFIIS1 and TbTFIIS2
      1 strongly suggests synthetical lethality and thus an essential function shared
      by the two proteins in trypanosome growth.

PMID- 18627465
TI  - Complement factor H allotype 402H is associated with increased C3b opsonization
      and phagocytosis of Streptococcus pyogenes.
AB  - The main virulence factor of group A streptococcus (GAS), M protein, binds plasma
      complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to
      decreased opsonization. The M protein binding site on FH is within domain 7 in
      which also the age-related macular degeneration (AMD)-associated polymorphism
      Y402H is located. We studied if FH allotypes 402H and 402Y have different binding
      affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment
      FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in
      human blood taken from FH(402H) homozygous individuals was decreased when
      compared with blood taken from FH(402Y) homozygous individuals. The effect of the
      allotype 402H can be explained by combining the previous M protein mutagenesis
      data and the recently published crystal structure of FH6-8. In conclusion the
      data indicate that the AMD-associated allotype 402H leads to diminished binding
      of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These
      results suggest that the homozygous presence of the allele 402H could be
      associated with decreased risk for severe GAS infections offering an explanation
      for the high frequency of the allele despite its association with visual
      impairment.

PMID- 18627466
TI  - The headful packaging nuclease of bacteriophage T4.
AB  - Most tailed bacteriophages and herpes viruses replicate genome as a concatemer
      which is cut by a 'headful' nuclease upon completion of genome packaging. Here,
      the catalytic centre of phage T4 headful nuclease, present in the C-terminal
      domain of 'large terminase' gp17, has been defined by mutational, biochemical and
      structural analyses. The crystal structure shows that this nuclease has an RNase
      H fold, suggesting that it cuts DNA by a two-metal ion mechanism. The active
      centre has a Mg ion co-ordinated by three acidic residues, D401, E458 and D542.
      Mutations at any of these residues resulted in loss of nuclease activity, but the
      mutants can package linear DNA. The gp17's nuclease activity is modulated by the
      'small terminase', gp16, by the N-terminal ATPase domain of gp17, and by the
      assembled packaging motor. These results lead to hypotheses concerning how phage
      headful nucleases cut the viral genomes before and after, but not during, DNA
      packaging.

PMID- 18627468
TI  - Microbial profile and drug resistance of Candida strains isolated from the blood
      of children: an 11-year study.
AB  - The latest observations indicate a continuous increase in the frequency of fungal
      infections, particularly in hospital patients, accompanied by changes in both the
      profile of the isolated strains and their drug susceptibility. The objective of
      this study was to evaluate the trend in the incidence of candidaemia and
      susceptibility of antifungal drugs in the Polish Mother's Memorial Hospital over
      an 11-year period. Blood samples taken from the hospitalised children were sent
      to the Department of Clinical Microbiology for diagnostic purposes. A total of
      195 Candida strains were isolated: 47.7%Candida albicans and 52.3% non-albicans.
      Candida parapsilosis was isolated in 65.7% of non-albicans strains. The
      prevalence of Candida spp. decreased from 16.9-20.5% in the years 1996-1997 to
      3.1-2.1% in the years 2005-2006. In the years 2000-2005, non-albicans strains
      were more prevalent. All C. albicans strains were susceptible to amphotericin B,
      2.94% of non-C. albicans strains were semisusceptible to amphotericin B, 98.92%
      of C. albicans and 85.29% of non-albicans strains were susceptible to 5
      fluorocytosine. Candida spp. strains are predominant pathogens in fungaemia in
      children in our hospital. Over the last few years,C. albicans have been replaced
      by non-albicans strains (predominantly C. parapsilosis), which exhibit a higher
      level of drug resistance. The number of Candida spp. isolated from blood
      decreased during the 11-year study.

PMID- 18627469
TI  - Susceptibility of Candida albicans to common and novel antifungal drugs, and
      relationship between the mating type locus and resistance, in Lebanese hospital
      isolates.
AB  - The incidence of antifungal resistance is on the increase worldwide and novel
      drugs are constantly being developed to counter this trend. One hundred and
      sixteen clinical isolates of Candida albicans were collected from Lebanese
      hospitals in order to first determine the degree of resistance of Lebanese
      isolates to four common azoles: fluconazole (FL), itraconazole (IT), ketoconazole
      (KE), and voriconazole (VO), in addition to amphotericin B (AP) and caspofungin
      (CS) through the Epsilometer test method and second, determine any relationship
      between the allelic compositions of the mating type loci (MTLa, MTL alpha,
      MTLa/alpha) with drug resistance. Results showed that resistance, among C.
      albicans isolates, was the highest with 12% for IT, followed by 7.7% for VO, 6%
      for KE, 5% for FL, 1.7% for AP and 0% for CS. Three isolates (2.6%) were
      resistant to all azoles tested, including one that was resistant to all drugs
      used except CS. Eleven isolates were homozygous at the MTL locus (9.5%), five of
      which (45%) were resistant to at least one antifungal drug whereas 14 of the 105
      heterozygous strains (13%) exhibited similar resistance (P = 0.02), indicating a
      strong correlation between MTL locus homozygosity and resistance.

PMID- 18627470
TI  - Pseudomembranous-like tinea of the scrotum: report of six cases.
AB  - Six cases of tinea of the scrotum with atypical clinical features were observed
      in the dermatology department of our hospital between 2001 and 2007. The age of
      onset ranged from 14 to 26 years. Unusual clinical presentations of
      pseudomembranous-like disease were observed in every patient. Causative agents
      were Microsporum gypseum in five patients and Trichophyton rubrum in one patient.
      Three of the M. gypseum isolates had atypical morphologies. All six isolates were
      identified by cultural morphologies and DNA sequence analysis of the internal
      transcribed spacer region of the ribosomal DNA.

PMID- 18627467
TI  - RecA-mediated SOS induction requires an extended filament conformation but no ATP
      hydrolysis.
AB  - The Escherichia coli SOS response to DNA damage is modulated by the RecA protein,
      a recombinase that forms an extended filament on single-stranded DNA and
      hydrolyzes ATP. The RecA K72R (recA2201) mutation eliminates the ATPase activity
      of RecA protein. The mutation also limits the capacity of RecA to form long
      filaments in the presence of ATP. Strains with this mutation do not undergo SOS
      induction in vivo. We have combined the K72R variant of RecA with another
      mutation, RecA E38K (recA730). In vitro, the double mutant RecA E38K/K72R
      (recA730,2201) mimics the K72R mutant protein in that it has no ATPase activity.
      The double mutant protein will form long extended filaments on ssDNA and
      facilitate LexA cleavage almost as well as wild-type, and do so in the presence
      of ATP. Unlike recA K72R, the recA E38K/K72R double mutant promotes SOS induction
      in vivo after UV treatment. Thus, SOS induction does not require ATP hydrolysis
      by the RecA protein, but does require formation of extended RecA filaments. The
      RecA E38K/K72R protein represents an improved reagent for studies of the function
      of ATP hydrolysis by RecA in vivo and in vitro.

PMID- 18627471
TI  - First case of continuous ambulatory peritoneal dialysis peritonitis due to
      Candida sake.
AB  - Fungal peritonitis is a relatively uncommon complication of peritoneal dialysis
      that contributes significantly to morbidity, drop out from the continuous
      ambulatory peritoneal dialysis (CAPD) program, and mortality. Candida sake
      infections were rarely published in literature. We present the first case of
      peritonitis due to C. sake. A 41-year-old man was admitted to our hospital with
      abdominal pain, nausea, vomiting, fever, weakness. Abdominal ultrasonography
      demonstrated a fistula tract, which has an opening at inferolateral of the
      umbilicus extending 5 cm from the skin into the abdominal cavity with a foreign
      body (11 x 10 mm length) inside the fistula. The foreign body was removed by
      surgery being apparently a part of a previously inserted peritoneal catheter.
      Postoperative specimens revealed polymorph leucocytes and yeast cells in Gram
      stain, and culture on Sabouraud dextrose agar (SDA) yielded a growth of a fungus,
      subsequently identified as C. sake with Api ID 32C. Fluconazole (200 mg/day)
      therapy was started. He recovered after two weeks of therapy. In conclusion, C.
      sake, a rare type of Candida species, should be considered as a probable
      peritoneal pathogen in patients with multiple episodes of bacterial peritonitis,
      previous broad-spectrum antibiotic therapy and diabetes mellitus.

PMID- 18627472
TI  - Growth of Candida species on complete dentures: effect of microwave disinfection.
AB  - Microwave disinfection of complete dentures has been recommended to treat denture
      stomatitis in non-immune compromised patients. Oral candidiasis is a frequent
      manifestation of HIV infection. The objective of this study is to evaluate the
      effectiveness of microwave irradiation on the disinfection of complete dentures
      inoculated with American Type Culture Collection (ATCC) and HIV isolates of five
      species of Candida. Fifty dentures were made, sterilised and inoculated with the
      tested microorganisms (C. albicans, C. dubliniensis, C. krusei, C. glabrata and
      C. tropicalis). After incubation (37 degrees C/48 h), dentures were microwaved
      (650 W/3 min). Non-irradiated dentures were used as positive controls. Replicate
      aliquots of suspensions were plated at dilutions 10(-1) to 10(-4) and incubated
      (37 degrees C/48 h). Colony counts (cfu ml(-1)) were quantified. Dentures were
      also incubated at 37 degrees C for 7 days. Data were analysed with 2-way ANOVA
      and Tukey HSD tests (alpha = 0.05). Dentures contaminated with all Candida
      species showed sterilisation after microwave irradiation. All control dentures
      showed microbial growth on the plates. The cfu ml(-1) for C. glabrata was higher
      than those of C. albicans, C. dubliniensis and C. tropicalis whereas the cfu ml(
      1) for C. krusei was lower. The cfu ml(-1) for clinical isolates was higher than
      those of ATCC yeast. Microwave irradiation for 3 min at 650 W resulted in
      sterilisation of all complete dentures.

PMID- 18627473
TI  - Carriage rate and virulence attributes of oral Candida albicans isolates from
      patients with oral lichen planus: a study in an ethnic Chinese cohort.
AB  - The objectives of this study are to investigate the carriage rate of Candida
      albicans from the patients with oral lichen planus (OLP, erosive and non-erosive
      subtypes) and the healthy control individuals in a Chinese cohort and then to
      compare the virulence attributes of these isolates. Oral C. albicans isolates
      from 300 patients with OLP as well as 128 healthy controls were isolated and a
      total of 112 isolates from patients with erosive OLP (62), non-erosive OLP (24)
      and healthy control (26) were screened for phospholipase activity by using an in
      vitro plate assay method. Adhesion ability of the above isolates was also studied
      by using buccal epithelial cells assay. Statistically, the carriage rate of C.
      albicans from the patients with erosive OLP (44.29%) was higher than that of
      patients with non-erosive OLP (15.00%) or the healthy control group (20.31%) (P <
      0.001). The adhesion to buccal epithelial cells of the isolates from the erosive
      OLP group (3.950 +/- 1.436) was more marked (P < 0.001) than that from healthy
      control (2.2112 +/- 0.4833). The phospholipase activity of these isolates either
      from erosive (0.4170 +/- 0.029) or non-erosive OLP groups (0.4327 +/- 0.028) was
      higher (P < 0.001) than that from healthy controls (0.5259 +/- 0.074). Some C.
      albicans isolates with special virulence attributes might be co-factors, which
      contribute to the development of OLP, especially erosive OLP.

PMID- 18627474
TI  - Isolation of Acremonium strictum from pleural fluid of a patient with colon
      adenocarcinoma.
AB  - Although Acremonium strictum is environmentally widespread as opportunistic
      fungus, it may cause infection in patients who have immunodeficiency. In this
      study, A. strictum were isolated from the pleural fluid of a patient with colon
      adenocarcinoma. The patient did not receive antifungal therapy because the
      patient died on the same day after the isolation of the mould from the pleural
      fluid. Major risk factors for the fungal infection are surgery because of cancer,
      administration of parenteral hyperalimentation and broad-spectrum antibiotics,
      attaching chest tube and ventilation tube and hospitalization in intensive care
      unit. The minimal inhibitory concentrations (MICs) of amphotericin B,
      fluconazole, ketoconazole, itraconazole, voriconazole for the A. strictum strain
      isolated from pleural fluid were 0.125, 256, 2, 1.5 and 0.25 microg ml(-1),
      respectively. In conclusion, bacteria and fungi, especially opportunistic fungi
      should be taken into consideration in the developing pleuritis in the patients
      with predisposing risks for the fungal infection.

PMID- 18627475
TI  - The expression of genes involved in the ergosterol biosynthesis pathway in
      Candida albicans and Candida dubliniensis biofilms exposed to fluconazole.
AB  - The expression of the ERG1, ERG3, ERG7, ERG9, ERG11 and ERG25 genes in response
      to incubation with fluconazole and biofilm formation was investigated using
      reverse-transcription PCR and real-time PCR in Candida albicans and Candida
      dubliniensis clinical isolates. The viability of biofilm was measured using an
      2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)
      reduction assay and confocal scanning laser microscopy (CSLM). Expression of the
      ERG11 gene was found to be low or moderate and it was regulated by fluconazole
      addition more so than by biofilm formation. Very low or non-detectable expression
      of ERG1, ERG7 and ERG25 genes was detected in C. albicans. The expression of the
      ERG9 increased in the presence of fluconazole in some isolates. Following
      incubation with fluconazole, formation of biofilm by C. dubliniensis was coupled
      with up-regulation of the ERG3 and ERG25 genes as have been observed previously
      in C. albicans. Planktonic cells of both Candida species released from biofilm
      displayed similar resistance mechanisms to fluconazole like attached cells. The
      XTT reduction assay and CSLM revealed that although incubation with fluconazole
      decreased the biofilm thickness, these were still comprised metabolically active
      cells able to disseminate and produce biofilm. Our data indicate that biofilm
      represents a highly adapted community reflecting the individuality of clinical
      isolates.

PMID- 18627476
TI  - Successful treatment for chromoblastomycosis caused by Fonsecaea monophora: a
      report of three cases in Guangdong, China.
AB  - Fonsecaea pedrosoi is the most prevalent aetiological agent of
      chromoblastomycosis. Fonsecaea monophora is a new species segregated from
      Fonsecaea pedrosoi. Herein, we report on three cases of chromoblastomycosis
      caused by F. monophora that were successfully treated with terbinafine and/or
      itraconazole. Clinical characteristics and mycological parameters are described.
      Two of the three patients underwent combination therapy with itraconazole and
      terbinafine during early stages of treatment and were completely healed in a
      relatively short course of treatment.

PMID- 18627477
TI  - Effects of Saccharomyces boulardii on cytokine secretion from intraepithelial
      lymphocytes infected by Escherichia coli and Candida albicans.
AB  - Saccharomyces boulardii (S. boulardii) is a probiotic and used in the prevention
      or treatment of diarrhoea. Saccharomyces boulardii has many mechanisms to protect
      the host against diarrhoeal pathogens. It might modulate the immune system. In
      this study, the influence of S. boulardii on the secretion of cytokines from
      intraepithelial lymphocytes (IELs) infected with Escherichia coli (E. coli) and
      Candida albicans (C. albicans) was investigated in vitro. Cytokine levels were
      determined by enzyme-linked immunosorbent assay. The secretion of proinflammatory
      cytokines such as interleukin (IL)-1beta was decreased in the infected IELs
      incubated with S. boulardii, but different from it, anti-inflammatory cytokine
      levels such as IL-4 and IL-10, however, were found to be higher. These findings
      demonstrated that S. boulardii may have protective effects against diarrhoeal
      pathogens by reducing the proinflammatory response.

PMID- 18627479
TI  - Tumor arising in the periventricular region.

PMID- 18627480
TI  - Peripheral nervous system pathology in fragile X tremor/ataxia syndrome (FXTAS).
AB  - Fragile X tremor/ataxia syndrome (FXTAS) occurs in individuals with moderate CGG
      expansion of the fragile X mental retardation 1 (FMR1) gene and is associated
      with intranuclear inclusions in neurons and astrocytes. Although the
      neuropathologic findings in the brain and spinal cord were described,
      pathological features in the peripheral nervous system were not reported. Here,
      we report on novel neuropathological findings in the peripheral nervous system
      and especially in autonomic ganglia at autopsy in a man with FXTAS. In addition
      to the characteristic brain and spinal cord findings, typical intranuclear
      inclusions were identified in the ganglion cells of adrenal medulla, dorsal root
      ganglia, paraspinal sympathetic ganglia, myenteric ganglia of the stomach and
      subepicardial autonomic ganglion of the heart. Our findings indicate that FXTAS
      diffusely involves the central and peripheral nervous systems, which explains the
      protean neurological symptoms ranging from dementia to dysautonomia.

PMID- 18627481
TI  - Chromosome 16q22.1-linked autosomal dominant cerebellar ataxia: an autopsy case
      report with some new observations on cerebellar pathology.
AB  - An autopsy case of chromosome 16q22.1-linked autosomal dominant cerebellar ataxia
      is reported. The patient was a 77-year-old man who died after a clinical course
      of about 19 years characterized by pure cerebellar ataxia. Main neuropathological
      findings included moderate loss of Purkinje cells, variegated degenerative
      features of the remaining Purkinje cells, finely fibrillary material surrounding
      the perikarya of Purkinje cells, and ubiquitin-immunoreactive small dots in the
      molecular layer and cerebellar white matter. Neuritic hyperplasia surrounding the
      perikarya of Purkinje cells was also a prominent finding. Golgi impregnation
      study demonstrated poor dendritic arborization of some Purkinje cells. It is our
      assumption that the pathological processes leading to Purkinje cell death in this
      disorder are not singular because the intracellular functions of the protein
      coded by the mutant gene are manifold, and the multiplicity of the pathological
      processes is reflected in diverse cytomorphological changes seen in degenerating
      Purkinje cells.

PMID- 18627482
TI  - Mature cerebellar teratoma in adulthood.
AB  - Extragonadal teratomas in adulthood are exceptionally rare and usually not
      located within the cerebellum. We here report on a 66-year-old male patient
      clinically presenting with chronic occipital headache and episodes of severe
      vertigo. Neuroradiological investigations revealed a hemorrhagic tumor mass in
      the cerebellar vermis which was surgically removed and histologically diagnosed
      as mature teratoma. Hence, the presented case is extraordinary with regard to
      age, late clinical onset of symptoms and cerebellar location. Late clinical
      manifestation of the tumor in this case is probably due to an acute late-onset
      hemorrhage within the tumor.

PMID- 18627483
TI  - Two region-dependent pathways of eosinophilic neuronal death after transient
      cerebral ischemia.
AB  - Various types of eosinophilic neurons (ENs) are found in the post-ischemic brain.
      We examined the temporal profile of ENs in the core and peripheral regions of the
      ischemic cortex, and analyzed the relationship to the expression of various cell
      death-related factors. Unilateral forebrain ischemia was induced in Mongolian
      gerbils by transient common carotid artery occlusions, and the brains from 3 h to
      2 weeks post-ischemia were prepared for morphometric and immunohistochemical
      analysis of ENs. ENs with minimally abnormal nuclei and swollen cell bodies
      appeared at 3 h in the ischemic core and at 12 h in the periphery. In both
      locations multiple cell death-related factors including calcium, micro-calpain,
      cathepsin D, 78 kDa glucose-regulated protein (GRP78) and ubiquitin were
      activated. In the ischemic core, pyknosis and irregularly atrophic cytoplasm
      peaked at 12 h, which was associated with significant increases in staining for
      calcium and micro-calpain. ENs with pyknosis and scant cytoplasm peaked at 4 days
      and were positive for TUNEL and calcium staining. In the ischemic periphery, ENs
      had slightly atrophic cytoplasm and sequentially developed pyknosis, karyorrhexis
      and karyolysis over 1 week. These cells were positive for TUNEL and calcium
      staining. All types of EN were negative for caspase 3. There may be two region
      dependent pathways of EN changes in the post-ischemic brain: pyknosis with
      cytoplasmic shrinkage in the core, and nuclear disintegration with slightly
      atrophic cytoplasm in the periphery. This difference coordinates different
      activation patterns of cell death-related factors in ENs.

PMID- 18627484
TI  - Anterior spinal cord infarction caused by fibrocartilaginous embolism.
AB  - Fibrocartilaginous embolism is a rare cause of anterior spinal cord infarction.
      We report a case of anterior spinal cord infarction caused by a
      fibrocartilaginous embolism of 3 months duration in a 23-year-old man. Ten days
      after a trivial strike to the neck and back, he had sudden back pain, weakness of
      the upper and lower extremities, developed dyspnea and became unconscious.
      Cervical MRI showed an enlargement of the lower medulla and cervical cord with
      abnormal signals in the ventral portion. The follow-up MRI performed 2 months
      later showed atrophy of the above lesion. On histopathological examination, there
      was a recent, extensive infarct in the cervical cord and lower medulla. The
      lesion was symmetrical, and predominantly involved the anterior part of the
      spinal cord. Moreover, many basophilic, alcian blue-positive emboli in the
      arteries and veins of the lesion were detected. This is the first autopsy case of
      anterior spinal cord infarction caused by a fibrocartilaginous embolism that has
      been confirmed in China. The clinicopathological features of this case are
      reviewed in this paper.

PMID- 18627485
TI  - Recurrent tumor in the suprasellar region of a 76-year-old woman.

PMID- 18627486
TI  - Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa.
AB  - Cytogenetic studies of choroid plexus tumors, particularly for atypical choroid
      plexus papillomas, have been rarely described. In the present report, the
      cytogenetic investigation of an atypical choroid plexus papilloma occurring at
      the posterior fossa of a 16-year-old male is described. Comparative genome
      hybridization analysis demonstrated gains of genetic material from almost all
      chromosomes. Chromosome losses involved 19p, regional losses at chromosome X and
      loss of chromosome Y. The presence of polyploid cells was confirmed by
      fluorescence in situ hybridization analysis with probes directed to centromeric
      regions. Furthermore, the microscopic analysis of cultures showed nuclear buds,
      nucleoplasmic bridges, and micronuclei in 23% of tumor cells suggesting the
      presence of complex chromosomal abnormalities. Previous cytogenetic studies on
      choroid plexus papillomas showed either normal, hypodiploid or hyperdiploid
      karyotypes. To the best of our knowledge, this is the first report of polyploidy
      in choroid plexus papilloma of intermediate malignancy grade. Although the
      mechanisms beneath such genome duplication remain to be elucidated, the observed
      abnormal nuclear shapes indicate constant restructuring of the tumor's genome and
      deserves further investigation.

PMID- 18627487
TI  - Expression of estrogen receptor alpha and beta in reactive astrocytes at the male
      rat hippocampus after status epilepticus.
AB  - Estrogen is neuroprotective against status epilepticus (SE)-induced hippocampal
      damage in female animals. In male animals, estrogen is converted from
      testosterone via aromatization the activity of which is upregulated by brain
      damage. However, it is controversial whether estrogen is neuroprotective or
      neuroinvasive against male hippocampal damage after SE. In order to understand
      the role of estrogen, it is important to elucidate the distribution manner of
      estrogen receptor (ER)alpha and beta as the targets of estrogen. In this study,
      we examined the time course changes of ERs in adult male rat hippocampus after SE
      using anti-ERalpha antibodies (MC-20 and PA1-309) and anti-ERbeta antibodies (PA1
      310B and PA1-311). In control rats, both ERalpha and beta were expressed in the
      pyramidal cells predominantly at CA1 and CA3. ERalpha was expressed in the
      cytoplasm and the nucleus, whereas ERbeta was expressed in the cytoplasm of the
      pyramidal cells. After SE, according to the pyramidal cell loss at CA1, the
      number of ERalpha- and beta-immunoreactive pyramidal cells decreased up to day
      21. On the other hand, reactive astrocytes, which newly appeared after SE and
      formed gliosis at CA1, were confirmed to express both ERs in the nucleus,
      cytoplasm, and process. There were no differences in immunoreactivity between
      antibodies. Our results indicate that endogenous estrogen affects the pyramidal
      cells through ERalpha and beta under normal circumstances in adult male rats,
      whereas the targets of estrogen shift to the reactive astrocytes through ERalpha
      and beta after SE.

PMID- 18627488
TI  - Methotrexate-related leukoencephalopathy without radiation therapy: distribution
      of brain lesions and pathological heterogeneity on two autopsy cases.
AB  - This report concerns two rare autopsy cases of methotrexate (MTX)-related
      leukoencephalopathy without radiation therapy. In the first case, there were
      widespread necrotic foci with prominent spheroids, that is, disseminated
      necrotizing leukoencephalopathy (DNL), mainly in the cerebral white matter. In
      contrast, in the second case, there were widespread demyelinated foci without
      significant axonal changes, which we would like to name disseminated
      demyelinating leukoencephalopathy (DDL), mainly in the cerebral white matter. We
      emphasize that the pathology of pure MTX-related leukoencephalopathy is not
      uniform, and may show at least two kinds of histologic change. Furthermore, both
      cases did not develop significant vascular changes, which are usually induced by
      radiation therapy. The distribution of the lesions in two cases was examined by
      large specimens, including hemisphere specimens. The distribution of the lesions
      in the brain of our cases was also different. In the first case, the DNL lesions
      were predominantly distributed in the frontal and temporal lobes. In the second
      case, the DDL lesions were prominently localized in the occipital lobe. To our
      knowledge, this is the first report describing not only the pathological findings
      of MTX-related leukoencephalopathy without irradiation but also the precise
      distributions of the lesions.

PMID- 18627489
TI  - Giving and receiving: measuring the carbon cost of  mycorrhizas in the green
      orchid, Goodyera repens.
AB  - Direct measurement of the carbon (C) 'cost' of mycorrhizas is problematic.
      Although estimates have been made for arbuscular and ectomycorrhizal symbioses,
      these are based on incomplete budgets or indirect measurements. Furthermore, the
      conventional model of unidirectional plant-to-fungus C flux is too simplistic.
      Net fungus-to-plant C transfer supports seedling establishment in c. 10% of plant
      species, including most orchids, and bidirectional C flows occur in
      ectomycorrhiza utilizing soil amino acids. Here, the C cost of mycorrhizas to the
      green orchid Goodyera repens was determined by measurement of simultaneous
      bidirectional fluxes of 14C labelled sources using a monoxenic system with the
      fungus Ceratobasidium cornigerum. Transfer of C from fungus to plant ('up-flow')
      occurs in the photosynthesizing orchid G. repens (max. 0.06 microg) whereas over
      five times more current assimilate (min. 0.355 microg) is simultaneously
      allocated in the reverse direction to the mycorrhizal fungus ('down-flow') after
      8 d. Carbon is transferred rapidly, being detected in plant-fungal respiration
      within 31 h of labelling. This study provides the most complete C budget for an
      orchid-mycorrhizal symbiosis, and clearly shows net plant-to-fungus C flux. The
      rapidity of bidirectional C flux is indicative of dynamic transfer at an
      interfacial apoplast as opposed to reliance on digestion of fungal pelotons.

PMID- 18627490
TI  - Pollinator responses to variation in floral display and flower  size in dioecious
      Sagittaria latifolia (Alismataceae).
AB  - In animal-pollinated plants with unisexual flowers, sexual dimorphism in floral
      traits may be the consequence of pollinator-mediated selection. Experimental
      investigations of the effects of variation in flower size and floral display on
      pollinator visitation can provide insights into the evolution of floral
      dimorphism in dioecious plants. Here, we investigated pollinator responses to
      experimental arrays of dioecious Sagittaria latifolia in which we manipulated
      floral display and flower size. We also examined whether there were changes in
      pollinator visitation with increasing dimorphism in flower size. In S. latifolia,
      males have larger flowers and smaller floral displays than females. Visitation by
      pollinators, mainly flies and bees, was more frequent for male than for female
      inflorescences and increased with increasing flower size, regardless of sex. The
      number of insect visits per flower decreased with increasing floral display in
      males but remained constant in females. Greater sexual dimorphism in flower size
      increased visits to male inflorescences but had no influence on the number of
      visits to female inflorescences. These results suggest that larger flower sizes
      would be advantageous to both females and males, and no evidence was found that
      females suffer from increased flower-size dimorphism. Small daily floral displays
      may benefit males by allowing extended flowering periods and greater
      opportunities for effective pollen dispersal.

PMID- 18627491
TI  - Capacities and constraints of amino acid utilization  in Arabidopsis.
AB  - Various amino acids, including both L- and D-enantiomers, may be present in
      soils, and recent studies have indicated that plants may access such nitrogen (N)
      forms. Here, the capacity of Arabidopsis to utilize different L- and D-amino
      acids is investigated and the constraints on this process are explored. Mutants
      defective in the lysine histidine transporter 1 (LHT1) and transgenic plants
      overexpressing LHT1 as well as plants expressing D-amino acid-metabolizing
      enzymes, were used in studies of uptake and growth on various N forms.
      Arabidopsis absorbed all tested N-forms, but D-enantiomers at lower rates than L
      forms. Several L- but no D-forms were effective as N sources. Plants deficient in
      LHT1 displayed strong growth reductions and plants overexpressing LHT1 showed
      strong growth enhancement when N was supplied as amino acids, in particular when
      these were supplied at low concentrations. Several D- amino acids inhibited
      growth of wild-type plants, while transgenic Arabidopsis-expressing genes
      encoding D-amino acid-metabolizing enzymes could efficiently utilize such
      compounds for growth. These results suggest that several amino acids, and in
      particular L-Gln and L-Asn, promote growth of Arabidopsis, and increased
      expression of specific amino acid transporters enhances growth on amino acids.
      The efficiency by which transgenic plants exploit D-amino acids illustrates how
      plants can be engineered to utilize specific N sources otherwise inaccessible to
      them.

PMID- 18627492
TI  - Foraging for space and avoidance of physical obstructions by plant roots: a
      comparative study of grasses from contrasting habitats.
AB  - Physical obstructions that reduce space for root growth can profoundly affect
      plant performance. The aim of this study was to investigate the ability of roots
      to avoid obstructions and forage for usable space, and to reveal the mechanism
      involved. Eight grass species from four genera were examined. Each genus included
      species characteristic of habitats with high and low nutrient availability. The
      ability to limit root mass and to adjust morphology within substrate containing
      obstructions in the form of gravel was investigated. A treatment with activated
      carbon, which adsorbs organic compounds, was used to examine the possible
      involvement of root exudates in responses to obstructions. Only species
      characteristic of nutrient-poor habitats restricted placement of root mass in
      substrate containing obstructions, and this response disappeared in the presence
      of activated carbon. Root morphological responses to obstructions differed from
      those shown in response to nutrient-poor conditions or compacted soil. These
      results suggest that the ability to avoid obstructions is dependent on the
      sensitivity of roots to their own exudates accumulating in the vicinity of
      obstructions. This is similar to other behavioural responses in which cues or
      signals are used to adjust growth before stressful conditions are encountered.

PMID- 18627493
TI  - The sugar porter gene family of Laccaria bicolor: function in ectomycorrhizal
      symbiosis and soil-growing hyphae.
AB  - Formation of ectomycorrhizas, a symbiosis with fine roots of woody plants, is one
      way for soil fungi to overcome carbohydrate limitation in forest ecosystems.
      Fifteen potential hexose transporter proteins, of which 10 group within three
      clusters, are encoded in the genome of the ectomycorrhizal model fungus Laccaria
      bicolor. For 14 of them, transcripts were detectable. When grown in liquid
      culture, carbon starvation resulted in at least twofold higher transcript
      abundances for seven genes. Temporarily elevated transcript abundance after sugar
      addition was observed for three genes. Compared with the extraradical mycelium,
      ectomycorrhiza formation resulted in a strongly enhanced expression of six genes,
      of which four revealed their highest observed transcript abundances in symbiosis.
      A function as hexose importer was proven for three of them. Only three genes, of
      which just one was expressed at a considerable level, revealed a reduced
      transcript content in mycorrhizas. From gene expression patterns and import
      kinetics, the L. bicolor hexose transporters could be divided into two groups:
      those responsible for uptake of carbohydrates by soil-growing hyphae, for
      improved carbon nutrition, and to reduce nutrient uptake competition by other
      soil microorganisms; and those responsible for efficient hexose uptake at the
      plant-fungus interface.

PMID- 18627494
TI  - Genome-wide analysis of a land plant-specific acyl:coenzyme A synthetase (ACS)
      gene family in Arabidopsis, poplar, rice and Physcomitrella.
AB  - The plant enzyme 4-coumarate:coenzyme A ligase (4CL) is part of a family of
      adenylate-forming enzymes present in all organisms. Analysis of genome sequences
      shows the presence of '4CL-like' enzymes in plants and other organisms, but their
      evolutionary relationships and functions remain largely unknown. 4CL and 4CL-like
      genes were identified by BLAST searches in Arabidopsis, Populus, rice,
      Physcomitrella, Chlamydomonas and microbial genomes. Evolutionary relationships
      were inferred by phylogenetic analysis of aligned amino acid sequences.
      Expression patterns of a conserved set of Arabidopsis and poplar 4CL-like acyl
      CoA synthetase (ACS) genes were assayed. The conserved ACS genes form a land
      plant-specific class. Angiosperm ACS genes grouped into five clades, each of
      which contained representatives in three fully sequenced genomes. Expression
      analysis revealed conserved developmental and stress-induced expression patterns
      of Arabidopsis and poplar genes in some clades. Evolution of plant ACS enzymes
      occurred early in land plants. Differential gene expansion of angiosperm ACS
      clades has occurred in some lineages. Evolutionary and gene expression data,
      combined with in vitro and limited in vivo protein function data, suggest that
      angiosperm ACS enzymes play conserved roles in octadecanoid and fatty acid
      metabolism, and play roles in organ development, for example in anthers.

PMID- 18627495
TI  - Potential contribution of natural enemies to patterns of local adaptation in
      plants.
AB  - Genetic differentiation among plant populations and adaptation to local
      environmental conditions are well documented. However, few studies have examined
      the potential contribution of plant antagonists, such as insect herbivores and
      pathogens, to the pattern of local adaptation. Here, a reciprocal transplant
      experiment was set up at three sites across Europe using two common plant
      species, Holcus lanatus and Plantago lanceolata. The amount of damage by the main
      above-ground plant antagonists was measured: a rust fungus infecting Holcus and a
      specialist beetle feeding on Plantago, both in low-density monoculture plots and
      in competition with interspecific neighbours. Strong genetic differentiation
      among provenances in the amount of damage by antagonists in both species was
      found. Local provenances of Holcus had significantly higher amounts of rust
      infection than foreign provenances, whereas local provenances of Plantago were
      significantly less damaged by the specialist beetle than the foreign provenances.
      The presence of surrounding vegetation affected the amount of damage but had
      little influence on the ranking of plant provenances. The opposite pattern of
      population differentiation in resistance to local antagonists in the two species
      suggests that it will be difficult to predict the consequences of plant
      translocations for interactions with organisms of higher trophic levels.

PMID- 18627496
TI  - Systemic induced resistance: a risk-spreading strategy in  clonal plant networks?
AB  - Clonal plant networks consist of interconnected individuals (ramets) of different
      sizes and ages. They represent heterogeneous ramet assemblages with marked
      differences in quality and attractiveness for herbivores. Here, feeding
      preferences of a generalist herbivore (Spodoptera exigua) for differently-aged
      ramets of Trifolium repens were studied, and changes in herbivore preference in
      response to systemic defense induction were investigated. Dual-choice tests were
      used to assess the preference of herbivores for young versus mature ramets of
      induced and uninduced plants, respectively. Additionally, leaf traits related to
      nutrition, biomechanics and chemical defense were measured to explain variation
      in tissue quality and herbivore preference. Young ramets were heavily damaged in
      control plants. After systemic defense induction, damage on young ramets was
      greatly reduced, while damage on mature ramets increased slightly. Defense
      induction increased leaf strength and thickness, decreased leaf soluble
      carbohydrates and substantially changed phenolic composition of undamaged ramets
      connected to attacked individuals. Systemic induced resistance led to a more
      dispersed feeding pattern among ramets of different ages. It is proposed that
      inducible defense acts as a risk-spreading strategy in clonal plants by
      equalizing herbivore preference within the clone, thereby avoiding extended
      selective feeding on valuable plant tissues.

PMID- 18627497
TI  - Simultaneous detection and quantification of the  unculturable microbe Candidatus
      Glomeribacter  gigasporarum inside its fungal host Gigaspora margarita.
AB  - A combined approach based on quantitative and nested polymerase chain reaction
      (qPCR and nPCR, respectively) has been set up to detect and quantify the
      unculturable endobacterium Candidatus Glomeribacter gigasporarum inside the
      spores of its fungal host Gigaspora margarita. Four genes were targeted, two of
      bacterial origin (23S rRNA gene and rpoB) and two from the fungus (18S rRNA gene
      and EF1-alpha). The sensitivity of the qPCR protocol has proved to be comparable
      to that of nPCR, both for the fungal and the bacterial detection. It has been
      demonstrated that the last detected dilution in qPCR corresponded, in each case,
      to 10 copies of the target sequences, suggesting that the method is equally
      sensitive for the detection of both fungal and bacterial targets. As the two
      targeted bacterial genes are predicted to be in single copy, it can be concluded
      that the detection limit is of 10 bacterial genomes for each mixture. The
      protocol was then successfully applied to amplify fungal and bacterial DNA from
      auxiliary cells and extraradical and intraradical mycelium. For the first time
      qPCR has been applied to a complex biological system to detect and quantify
      fungal and bacterial components using single-copy genes, and to monitor the
      bacterial presence throughout the fungal life cycle.

PMID- 18627498
TI  - Comparative community physiology: nonconvergence in water relations among three
      semi-arid shrub communities.
AB  - Plant adaptations to the environment are limited, and therefore plants in similar
      environments may display similar functional and physiological traits, a pattern
      termed functional convergence. Evidence was examined for functional convergence
      among 28 evergreen woody shrubs from three plant communities of the semi-arid
      winter rainfall region of southern California. Both leaf and water relations
      traits were examined, including seasonal stomatal conductance (gs), specific leaf
      area (SLA), leaf specific conductivity (Kl), seasonal water potential (Psi w),
      stem cavitation resistance (Psi 50), and xylem density. Species display community
      specific suites of xylem and leaf traits consistent with different patterns of
      water use among communities, with coastal sage scrub species utilizing shallow
      pulses of water, Mojave Desert scrub species relying on deeper water reserves,
      and chaparral species utilizing both shallow and deep moisture reserves.
      Communities displayed similar degrees of water stress, with a community-level
      minimum Psi w (Psi wmin) of c. -4.6 Mpa, similar to other arid communities.
      Pooled across sites, there was a strong correlation between Psi wmin and xylem
      density, suggesting that these traits are broadly related and predictive of one
      another. This comparative community physiology approach may be useful in testing
      hypotheses of functional convergence across structurally similar semi-arid
      communities.

PMID- 18627499
TI  - Intraspecific competition reveals conditional fitness effects  of single gene
      polymorphism at the Arabidopsis root  growth regulator BRX.
AB  - Intraspecific genetic variation for morphological traits is observed in many
      organisms. In Arabidopsis thaliana, alleles responsible for intraspecific
      morphological variation are increasingly being identified. However, the fitness
      consequences remain unclear in most cases. Here, the fitness effects of alleles
      of the BRX gene are investigated. A brx loss-of-function allele, which was found
      in a natural accession, results in a highly branched but poorly elongated root
      system. Comparison between the control accession Sav-0 and an introgression of
      brx into this background (brxS) indicated that, surprisingly, brx loss of
      function did not negatively affect fitness in pure stands. However, in mixed,
      well-watered stands brxS performance and reproductive output decreased
      significantly, as the proportion of Sav-0 neighbors increased. Additional
      comparisons between brxS and a brxS line that was complemented by a BRX transgene
      confirmed a direct effect of the loss-of-function allele on plant performance, as
      indicated by restored competitive ability of the transgenic genotype. Further,
      because plant height was very similar across genotypes and because the
      experimental setup largely excluded shading effects, the impaired competitiveness
      of the brx loss-of-function genotype likely reflects below-ground competition. In
      summary, these data reveal conditional fitness effects of a single gene
      polymorphism in response to intraspecific competition in Arabidopsis.

PMID- 18627500
TI  - Changing patterns of diet, physical activity and obesity among urban, rural and
      slum populations in north India.
AB  - Rapid urbanization and accompanying lifestyle changes in India lead to transition
      in non-communicable disease risk factors. A survey was done in urban, urban slum
      and rural population of Haryana, India, in a sample of 4129 men and 3852 women
      using WHO STEPS questionnaire. A very high proportion of all the three
      populations reported inadequate intake of fruits and vegetables. Rural men
      reported five times physical activity as compared with urban and urban slum men
      and rural women reported seven times physical activity as compared with women in
      the other two settings. Mean body mass index (BMI) was highest among urban men
      (22.8 kg m(-2)) followed by urban slum (21.0 kg m(-2)) and rural men (20.6 kg m(
      2)) (P-value < 0.01). Similar trend was seen for women but at a higher level than
      men. Prevalence of obesity (BMI >/= 30 kg m(-2)) was highest for urban population
      (male = 5.5%, female = 12.6%) followed by urban slum (male = 1.9%, female = 7.2%)
      and rural populations (male = 1.6%, female = 3.8%). Urbanization increases the
      prevalence of the studied non-communicable disease risk factors, with women
      showing a greater increase as compared with men. Non-communicable disease control
      strategy needs to address urbanization and warrants gender sensitive strategies
      specifically targeting women.

PMID- 18627501
TI  - Tooth abnormalities and soft tissue alterations in patients with G/BBB syndrome.
AB  - OBJECTIVE: The G/BBB syndrome is an X-linked recessive disorder characterized by
      eye anomalies, laryngotracheoesophageal cleft, congenital heart disease,
      genitourinary anomalies and gastrointestinal disorders. Patients may also present
      cleft lip and palate, high-arched palate and thin upper lip. This study aimed to
      investigate the occurrence of tooth abnormalities and soft tissue changes in
      patients with G/BBB syndrome. DESIGN: Cross-sectional. SUBJECTS AND METHODS:
      Twenty-one patients with G/BBB syndrome were analyzed as to the presence of tooth
      abnormalities and soft tissue alterations. MAIN OUTCOME MEASURES: The prevalence
      of tooth agenesis and supernumerary teeth was compared to patients without
      morphofunctional alterations, matched for gender and age. RESULTS: All patients
      had complete cleft lip and palate; 95.23% of patients presented tooth
      abnormalities, mainly hypoplastic alterations, with predominance of alterations
      of number, followed by alterations of structure, shape and position. The
      frequency of tooth agenesis and supernumerary teeth was significantly higher
      compared with the control group; 11 patients presented incisiform supernumerary
      teeth in the mandibular anterior region. Ankyloglossia was observed in 11 of 21
      patients. CONCLUSION: The presence of mandibular anterior supernumerary teeth and
      ankyloglossia should be investigated in the clinical evaluation of patients with
      suspected diagnosis of the G/BBB syndrome.

PMID- 18627502
TI  - Expression of human beta-defensin -1, -2, and -3 in non-inflamed pseudocyst,
      mucoceles.
AB  - OBJECTIVES AND DESIGN: The expressions of human beta defensin-1 (HBD-1), -2 (HBD
      2) and -3 (HBD-3) in non-inflamed pseudocysts such as mucoceles were investigated
      immunohistochemically in this study. MATERIALS AND METHODS: Mucocele specimens
      were obtained from 21 patients. The expression of HBDs was studied
      immunohistochemically by using antibodies directed against HBD-1, -2, and -3.
      Statistical analyses were carried out on serial sections stained with antibodies.
      RESULTS: Cells expressing HBDs were found in mucoceles. The expression of HBD-2
      was observed in floating cells in all the specimens, whereas HBD-1 and HBD-3
      expressing cells were detected in 93% and 73% of the mucoceles, respectively. The
      HBD-2 signal was the most intense and the HBD-3 signal intensity was weaker than
      that of HBD-1. HBDs were expressed in neutrophils and in other floating cells.
      Interestingly, the signal intensity and the population of positive cells located
      close to the centers of cysts were higher than those located in the peripheral
      areas of cysts. CONCLUSION: The expression of HBDs was found even in non-inflamed
      pseudocysts such as mucoceles. These results suggest that an unknown mechanism
      not involved in biophylaxis for the expression of HBDs may exist.

PMID- 18627503
TI  - Root development of rat tooth germs implanted in the tooth socket and in the
      subcutaneous tissue.
AB  - OBJECTIVE: This study was designed to investigate root development of a rat tooth
      germ implanted in a tooth socket or in a subcutaneous region. MATERIALS AND
      METHODS: Tooth germs of the upper left first molars in 2-week-old rats were
      extracted and implanted in the original tooth socket or in the subcutaneous
      region of the back. The upper right first molar was used as a control. The rats
      were fixed in weeks 1, 2, 4, 8 and 12. The root development was examined
      quantitatively with X-ray radiographic morphometry. The cellular activity of
      producing matrix proteins was assessed using in situ hybridization for type I
      collagen. RESULTS: Root development was observed in the implanted teeth in the
      tooth socket as also in the control teeth. In contrast, roots hardly developed in
      subcutaneously implanted teeth. Histology showed that periodontal ligaments were
      arranged around roots of implanted teeth in the tooth socket as around control
      teeth, but few periodontal ligaments were identified in the subcutaneous
      implantation. Dentin and cementum formed in both the implanted teeth as also in
      the control teeth and odontoblasts, cementoblasts and cementocytes expressed type
      I collagen. CONCLUSION: Tooth sockets may possess specific environments that
      allow root development of a tooth germ.

PMID- 18627504
TI  - A randomized clinical trial of chlorhexidine in the maintenance of oral
      candidiasis-free period in HIV infection.
AB  - OBJECTIVE: To determine if chlorhexidine can be used as an intervention to
      prolong the time to relapse of oral candidiasis. SUBJECTS AND METHODS: A double
      blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral
      candidiasis. Clotrimazole troche was prescribed, and the subjects were re
      examined every 2 weeks until the lesions were completely eradicated. The subjects
      were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22
      52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean
      38 years). They were re-examined every 2 weeks until the next episode was
      observed. RESULTS: The time to recurrence of oral candidiasis between the
      chlorhexidine and the saline group was not statistically significant (P > 0.05).
      The following variables were significantly associated with the time of
      recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P =
      0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048).
      The subjects with lower lymphocyte showed shorter oral candidiasis-free periods
      (P = 0.034). CONCLUSIONS: Chlorhexidine showed a small but not statistically
      significant effect in maintenance of oral candidiasis-free period. This lack of
      significance may be due to the small sample size. Further study should be
      performed to better assess the size of the effect, or to confirm our findings.

PMID- 18627505
TI  - Periodontal status in patients with pemphigus vulgaris.
AB  - OBJECTIVE: The aim of this study was to evaluate the periodontal status of
      pemphigus vulgaris (PV) patients and compare it with that of healthy controls. We
      also analysed the association between the periodontal condition and the clinical
      severity of the disease in PV patients. STUDY DESIGN: Twenty patients (nine
      women, 11 men; mean +/- s.d. age, 42.9+/-9.8 years) with PV and 22 healthy
      subjects (eight women, 14 men; mean +/- s.d. age, 40.5 +/- 12.1 years) were
      included in the study. The periodontal status of all subjects was evaluated
      according to the Community Periodontal Index of Treatment Needs (CPITN). PV
      patients were also assessed for Clinical Severity Score (CSS). RESULTS: The mean
      CPITN values were observed to be higher in PV patients (2.8 +/- 0.7) compared
      with those of healthy controls (1.0 +/- 0.8) (P < 0.001). Nevertheless, there was
      no statistically significant difference in CPITN values according to the CSS (P =
      0.4). The number of carious teeth was significantly higher in PV patients than
      that in healthy subjects. CONCLUSIONS: Our results showed that periodontal status
      is worse in PV patients. Moreover, PV might contribute to the development and /
      or progression of periodontitis. PV patients should be encouraged for long-term
      periodontal follow up.

PMID- 18627506
TI  - Characterization of rat bone marrow dendritic cells initially primed  by 
      Trichinella spiralis  antigens.
AB  - Pathogen-derived products have the capacity to induce maturation of bone marrow
      derived dendritic cells (BMDCs)into populations of effectors cells that polarize
      Th cells toward Th1 or Th2 phenotype via different mechanisms. Since those
      mechanisms are not entirely clear for helminths, and almost completely unknown
      for Trichinella spiralis(TS), we started an investigation of the effects of TS
      antigens (four different antigens isolated from all three life-cycle stages of
      parasite)on maturation of BMDCs and their potential to present TS antigens. The
      expression of MHC class II, costimulatory molecules CD86, CD54, IL-10 and IL
      12p70 cytokine production were measured after 2 days of BMDCs cultivation with TS
      antigens. While parasitic antigens did not significantly alter the expression of
      MHC II, most of them, except crude muscle larvae antigens, up-regulated the
      expression of costimulatory molecules. BMDCs, primed with all TS antigens,
      released increased amounts of IL-10 and decreased amounts of IL-12p70. BMDCs,
      primed with TS antigens, induced significant proliferation of syngeneic TS
      sensitized lymph nodes cells and also stimulated the production of IL-4 by T
      cells purified from of TS infected DA rats. The results indicate that TS
      stimulated BMDCs leads to the polarization of the immune response towards
      regulatory and Th2 type.

PMID- 18627507
TI  - Blood-brain barrier impairment with enhanced SP, NK-1R, GFAP and claudin-5
      expressions in experimental cerebral toxocariasis.
AB  - Infection by Toxocara canis in humans may cause cerebral toxocariasis (CT).
      Appreciable numbers of T. canis larvae cross the blood-brain barrier (BBB) to
      invade the brain thus causing CT. In the present studies, we evaluated the BBB
      permeability and BBB injury as assessed by the cerebral Evans blue (EB)
      concentration as well as by pathological changes and glial fibrillary acidic
      protein (GFAP) expression in T. canis -infected mice monitored from 3 days (dpi)
      to 8 weeks post-infection (wpi). The vasodilation neuropeptides, the expressions
      of substance P (SP) and its preferred binding neurokinin-1 receptor (NK-1R) as
      well as claudin-5 of tight-junction proteins associated with BBB impairment were
      also assessed by Western blotting and reverse-transcriptase polymerase chain
      reaction. Results revealed that BBB permeability increased as evidenced by a
      significantly elevated EB concentration in brains of infected mice. BBB injury
      appeared due to enhanced GFAP protein and mRNA expressions from 4 to 8 wpi.
      Leukocytes might have been unrelated to BBB impairment because there was no
      inflammatory cell infiltration despite T. canis larvae having invaded the brain;
      whereas markedly elevated SP protein and NK-1R mRNA expressions concomitant with
      enhanced claudin-5 expression seemed to be associated with persistent BBB
      impairment in this experimental CT model.

PMID- 18627508
TI  - Different effect of   Toxoplasma gondii   infection on adhesion capacity   of
      fibroblasts and monocytes.
AB  - This study investigated the effect of infection with the apicomplexan parasite
      Toxoplasma gondii, in combination with the concomitant cytokine environment (IFN
      gamma/TNF-alpha), on adhesion of THP-1 monocytic cells to MRC-5 fibroblasts.
      Surprisingly, infection of THP-1 cells decreased their adhesion to the MRC-5 cell
      monolayer. This decrease was compensated by IFN-gamma/TNF-alpha stimulation. In
      contrast, infection of MRC-5 cells significantly increased adhesion, which was
      synergistically augmented by cytokine stimulation. Levels of ICAM-1 (CD54) on MRC
      5 cells, as well as LFA-1 (CD11a) on THP-1 cells, were not changed by infection,
      neither in resting, nor in cytokine stimulated cells. These results show that T.
      gondii infection alters adhesion properties and reactivity to cytokine
      stimulation in a cell-specific way.

PMID- 18627509
TI  - In pregnant mice, the infection of Toxoplasma gondii causes the decrease of
      CD4+CD25+ -regulatory T cells.
AB  - Acute maternal infection with Toxoplasma gondii during pregnancy is associated
      with adverse pregnancy outcomes. Although previous reports have indicated that T.
      gondii may result in abortion without direct transmission of the parasite to the
      foetus, the molecular mechanism remains unclear. CD4+CD25+-regulatory T cells are
      known to be involved in maternal tolerance toward the foetus-bearing
      alloantigens. With a model of pregnant mice infected with T. gondii, we found
      that Foxp3 mRNA expression levels in both splenocytes and placenta were reduced
      markedly during the process of infection. Furthermore, the numbers of splenic
      CD4+CD25+-regulatory T cells and placental Foxp3+ cells decreased synchronously
      in the infected mice, and the reduction of splenic CD4+CD25+-regulatory T cells
      were associated with apoptosis induced by the infection. Additionally, injection
      of pregnant mice with excretory-secretory antigens (ESA) of T. gondii also
      resulted in foetal loss, which could be partly prevented by adoptive transfer of
      CD4+CD25+-regulatory T cells from normal pregnant mice. These data suggest that
      foetal loss caused by T. gondii can be independent of vertical infection and that
      the decrease of CD4+CD25+-regulatory T cells during infection may represent a
      previously unrecognized mechanism for the pathogenesis of abortion caused by this
      parasite.

PMID- 18627510
TI  - Delayed- and immediate-type reactions in the atopy patch test with food allergens
      in young children with atopic dermatitis.
AB  - In recent years, the atopy patch test (APT) has been suggested as an addition in
      the allergological work-up of children with atopic dermatitis (AD) and suspected
      food allergy. We initiated a prospective clinical study in children with AD
      younger than 3 yr, to evaluate the additional clinical value of the APT next to
      our own standardized allergological work-up in case of a suspected food allergy.
      One hundred and thirty-five children were included in the study. They were tested
      using the skin application food test (SAFT), the APT and measurement of specific
      IgE. The allergens used in the skin tests were freshly prepared food stuffs and
      included commercially available cow's milk (CM), the egg white of a hard boiled
      hen's egg and mashed peanuts in a saline solution. Allergy was defined using a
      flowchart incorporating the results from the SAFT, oral challenges (OCs) and
      elimination and (re)introduction periods. To determine the additional value of
      the APT next to the SAFT, we analyzed the SAFT negative patients per allergen and
      used an exact binary logistic analysis to evaluate the simultaneous effects of
      the APT and measurement of specific IgE, calculating mutually adjusted odds
      ratios (ORs) for positive APTs and specific IgE levels above 0.70 U/l. We found
      clinically relevant food allergies in 23% (egg white) to 28% (CM and peanut) of
      our study population. Positive SAFT reactions were observed in 14% (peanut), 16%
      (egg white) and 21% (CM) of our patient population. Next to the SAFT, we did not
      observe a significant additional value of the APT for the diagnosis of CM or egg
      white allergy, but we did find a significant additional value for the diagnosis
      of peanut allergy (OR = 11.56; p < 0.005, 2-sided). In clinical practice this
      statistically significant value does not exclude the need for OC and controlled
      elimination and (re)introduction periods due to the presence of false-negative as
      well as false-positive results in the APT. In conclusion, we could not find
      enough support for the current addition of the APT to our standardized
      allergological work-up in young children below the age of 3 yr with AD and
      suspected food allergy. At the moment the additional value of the classical
      delayed-type APT next to the SAFT seems to be very limited at best in this study
      population and does not justify the time-consuming nature of the skin test.

PMID- 18627511
TI  - Chronic active Epstein-Barr virus infection with mosquito allergy successfully
      treated with reduced-intensity unrelated allogeneic bone marrow transplantation
      in a boy.
AB  - EBV-infected T-/NK cells play an important role in the pathogenesis of mosquito
      allergy, and the prognosis of most patients with mosquito allergy is poor without
      proper treatment. We describe a 13-yr-old boy who had CAEBV with mosquito allergy
      and was successfully treated with BMT from an unrelated donor after reduced
      intensity preconditioning. Because combination chemotherapy failed to achieve CR,
      we performed unrelated BMT to reconstitute normal immunity and eradicate any
      residual EBV-infected cells. To reduce complications after BMT, we selected a
      reduced-intensity preconditioning regimen consisting of fludarabine, l
      phenylalanine mustard, and antithymocyte Ig instead of a conventional
      myeloablative preconditioning. Although grade II acute GVHD developed, it was
      successfully controlled with immunosuppressive therapy. After 27 months, the
      patient has been well without any signs of CAEBV, and the EBV DNA has been
      undetectable with real-time PCR analysis. We conclude that RIST from the bone
      marrow of an unrelated donor is indicated for some patients who have CAEBV that
      is refractory to chemotherapy and who have no HLA-matched related donors or cord
      blood as a source of stem cells.

PMID- 18627513
TI  - Successful unrelated cord blood transplantation for chronic granulomatous
      disease: a case report and review of the literature.
AB  - CGD is a rare inherited immunodeficiency disorder that is caused by disability of
      oxidative killing. We presented a two-yr-old boy with CGD who was suffering from
      multiple systemic abscesses. He received the first BMT from his HLA
      haploidentical mother after conditioning with Flu, melphalan, and ATG. Although
      the maximum of 42% donor chimerism was achieved, it disappeared 73 days after the
      BMT. Then, we performed 5/6-matched unrelated cord blood re-transplantation after
      conditioning with Flu, Bu, and TBI (2 Gy). Engraftment and complete donor
      chimerism were achieved on days 18 and 19, respectively. The patient is now free
      from infection and maintains complete donor chimerism without GVHD 36 months
      after the cord blood re-transplantation. We postulate that the unrelated CBT has
      a potential to be an alternative strategy and might be beneficial for patients
      with CGD who do not have an HLA-identical donor.

PMID- 18627512
TI  - Comparable outcomes of HLA-matched unrelated and HLA-identical sibling donor bone
      marrow transplantation for childhood acute myeloid leukemia in first remission.
AB  - We retrospectively investigated the outcomes of HLA-matched unrelated BMT (MU
      BMT, n = 13) and HLA-identical sibling donor BMT (MS-BMT, n = 17) for childhood
      AML in CR1 between June 2002 and August 2005. Engraftment of neutrophil and
      platelet did not differ between the two transplant groups. The cumulative
      incidence of grade II-IV acute GVHD and any chronic GVHD at three yr was not
      different between MS-BMT and MU-BMT. Of the 30 patients, four patients
      experienced relapses (three with MS-BMT, one with MU-BMT) and four patients died
      of transplant-related complications (two with MS-BMT, two with MU-BMT). A total
      of 23 patients survived with a median follow-up of 43.2 months. The Kaplan-Meier
      estimates for EFS rates at three yr were 71% and 77% for MS-BMT and MU-BMT,
      respectively, and the OS rates were 76% and 77% for MS-BMT and MU-BMT,
      respectively. The outcome of HLA-matched unrelated BMT is comparable to that of
      HLA-identical sibling BMT for childhood AML in CR1. HLA-matched unrelated BMT may
      be recommended for patients who have AML in CR1 without an HLA-matched sibling
      donor.

PMID- 18627514
TI  - Influence of cytokine and intercellular adhesion molecule-1 gene polymorphisms on
      acute rejection in pediatric renal transplantation.
AB  - Immune response regulation by cytokines is a key to understanding AGR. The
      influence of the functional polymorphisms in genes coding for TNF-alpha (-308G >
      A), IL-10 (-819C > T, and -1082A > G), IFN-gamma [(CA)n], TGF-beta1 (+869T > C),
      and iCAM-1 (R241G and E469K), in addition to HLA and gender matching on the
      presentation of AGR in 51 pediatric renal recipients during a 36-month post
      transplantation follow-up were analyzed. Also, donors and a control group were
      genotyped. All groups were within Hardy-Weinberg equilibrium for all
      polymorphisms except IL-10-819C > T and TNF-alpha (p < 0.005 and p < 0.01,
      respectively) in recipients. Transplants with gender mismatch showed a higher
      risk for AGR than those between individuals with gender match (OR, 4.227; p =
      0.010). Recipients with a high-production compared with low-production TNF-alpha
      allele experienced earlier AGR (p = 0.030), and those with high-production
      alleles of both TNF-alpha and IFN-gamma showed a further increased risk (OR =
      11.129, p = 0.024). These findings support the notion that a single genotype
      cannot by itself explain an event as complex as AGR. The sum or combination of
      different specific alleles of these genes could better account for the immune
      response to an allograft.

PMID- 18627515
TI  - Interactive transport, subcellular relocation and enhanced phototoxicity of
      hypericin encapsulated in guanidinylated liposomes via molecular recognition.
AB  - Hypericin (HYP), a photocytotoxic phenanthroperylenquinone was encapsulated in
      liposomes outfitted with guanidinium-bearing lipids to ensure efficient cell
      binding through molecular recognition with anionic groups resident on the plasma
      membrane. The uptake of HYP encapsulated in these liposomes by DU145 human
      prostate cancer cells, was studied employing fluorescence, versus nonguadinylated
      liposomes and free HYP. The subcellular localization was in all cases studied by
      confocal microscopy employing specific subcellular organelle probes. The
      photocytotoxicity of HYP was assessed, 24 h following irradiation with 15 mWcm(
      2) light through a GG 495 Schott filter, by a standard tetrazolium to formazan
      assay (XTT). HYP uptake by DU145 cells was found to be profoundly enhanced by
      using guanidinylated liposomes. Also the distance of the guanidinium group from
      the liposomal surface was found to significantly affect HYP loading, subcellular
      localization and phototoxicity. The two different modes of liposome cell
      internalization observed, i.e. plasma membrane fusion and endocytosis, were found
      to greatly affect the phototoxicity of HYP. Molecular recognition was overall
      appraised as a promising, novel route for photodynamic therapy, profoundly
      enhancing its efficacy. HYP encapsulated in liposomes-bearing guanidinium groups
      was more efficiently taken up by cells, leading to enhanced phototoxicity, in
      contrast to HYP encapsulated in their nonguanidinylated counterparts.

PMID- 18627516
TI  - Measurement of lens protein aggregation in vivo using dynamic light scattering in
      a guinea pig/UVA model for nuclear cataract.
AB  - The role of UVA radiation in the formation of human nuclear cataract is not well
      understood. We have previously shown that exposing guinea pigs for 5 months to a
      chronic low level of UVA light produces increased lens nuclear light scattering
      and elevated levels of protein disulfide. Here we have used the technique of
      dynamic light scattering (DLS) to investigate lens protein aggregation in vivo in
      the guinea pig/UVA model. DLS size distribution analysis conducted at the same
      location in the lens nucleus of control and UVA-irradiated animals showed a 28%
      reduction in intensity of small diameter proteins in experimental lenses compared
      with controls (P < 0.05). In addition, large diameter proteins in UVA-exposed
      lens nuclei increased five-fold in intensity compared to controls (P < 0.05). The
      UVA-induced increase in apparent size of lens nuclear small diameter proteins was
      three-fold (P < 0.01), and the size of large diameter aggregates was more than
      four-fold in experimental lenses compared with controls. The diameter of
      crystallin aggregates in the UVA-irradiated lens nucleus was estimated to be 350
      nm, a size able to scatter light. No significant changes in protein size were
      detected in the anterior cortex of UVA-irradiated lenses. It is presumed that the
      presence of a UVA chromophore in the guinea pig lens (NADPH bound to zeta
      crystallin), as well as traces of oxygen, contributed to UVA-induced crystallin
      aggregation. The results indicate a potentially harmful role for UVA light in the
      lens nucleus. A similar process of UVA-irradiated protein aggregation may take
      place in the older human lens nucleus, accelerating the formation of human
      nuclear cataract.

PMID- 18627517
TI  - Photosensitized oxidation of hypoxanthine and xanthine by aluminum phthalocyanine
      tetrasulfonate. Role of the alkylating quinone 2,5-dichloro-diaziridinyl-1,4
      benzoquinone.
AB  - Photoirradiation of nitrogen-saturated aqueous solutions containing aluminum
      phthalocyanine tetrasulfonate (AlPcS4) at 675 nm in the presence of 2,5-dichloro
      diaziridinyl-1,4-benzoquinone (AZDClQ) and hypoxanthine (HX) produces the
      oxidized HX derivatives, xanthine (X) and uric acid (UA). Concentrations of the
      AZDClQ semiquinone, X and UA increase at the expense of HX with an increase in
      irradiation time. Almost negligible decomposition of HX, as well as very low
      amounts of X, are detected if photolysis occurs under identical conditions but in
      the absence of AZDClQ. Addition of calf-thymus DNA produces quinone-DNA covalent
      adducts after photolysis of anaerobic samples containing quinone, DNA and AlPcS4,
      in the presence or absence of HX and at pH 5.5. However, larger amounts of
      quinone-DNA adducts are detected if HX is present. The results presented here
      could have applications in the photodynamic treatment of hypoxic tissues such as
      solid tumors, under conditions of high HX concentration, where Type-I pathways
      could be more important than singlet oxygen generation.

PMID- 18627518
TI  - Overview of the inactivation by 254 nm ultraviolet radiation of bacteria with
      particular relevance to biodefense.
AB  - Our goal was to ultimately predict the sensitivity of untested bacteria
      (including those of biodefense interest) to ultraviolet (UV) radiation. In this
      study, we present an overview and analysis of the relevant 254 nm data previously
      reported and available in the literature. The amount of variability in this data
      prevented us from determining an "average" response for any bacterium. Therefore,
      we developed particular selection criteria to include the data in our analysis
      and suggested future guidelines for reporting UV sensitivity results. We then
      compiled a table of the sensitivity to 254 nm UV for 38 bacteria and three
      bacterial spores. The UV sensitivity was quite similar (within 10%) among the
      spores of Bacillus anthracis (strains Vollum 1B and Sterne), Bacillus subtilis,
      and Bacillus megaterium. These data indicate that spores of B. subtilis and B.
      megaterium could be adequate simulants of B. anthracis spores in UVC experiments.
      Spores of B. anthracis, B. subtilis and B. megaterium were 5-10 times more
      resistant to UV than were their corresponding vegetative cells. The vegetative
      cells of B. anthracis showed similar UV sensitivity to those of Burkholderia
      pseudomallei, Shigella sonnei, and a wild-type strain of Escherichia coli.
      Yersinia enterocolitica and Vibrio cholerae appeared more sensitive to UV and
      Salmonella typhi slightly more resistant to UV than E. coli. The sensitivity (at
      254 nm) of all vegetative bacteria ranged from 11 to 80 Jm(2) for a 1 Log(10)
      kill and from 25-200 Jm(2) for 4 Log(10) kill.

PMID- 18627519
TI  - Algorithm for in vitro Sun Protection Factor based on transmission spectrum
      measurement with concomitant evaluation of photostability.
AB  - In the in vitro evaluation of Sun Protection Factor (SPF), the photostability of
      the ultraviolet (UV) filters can have a major impact, especially for high-SPF
      formulations, but is generally not taken into consideration. In this study, we
      present a UV transmission spectrum measurement system utilizing a high
      sensitivity UV photomultiplier tube with concomitant evaluation of
      photostability. We have developed an algorithm to estimate SPF in vitro by
      converting the amount of UV light transmission through the sunscreen layer into
      cumulative relative erythema effectiveness to obtain one minimal erythema dose.
      Thus, the algorithm uses the same endpoint as in vivo SPF methods, but with a
      photomultiplier tube as the detector instead of skin. The values obtained showed
      an excellent correlation with in vivo SPF values, even for high-SPF sunscreens
      exceeding SPF 50. This method should be suitable as an in vitro SPF testing
      method for regulatory purposes.

PMID- 18627520
TI  - Mechanism of UV-induced IkappaBalpha-independent activation of NF-kappaB.
AB  - Nuclear factor-kappa B (NF-kappaB) plays an important role in UV-induced skin
      tumorigenesis. Activation of NF-kappaB by UV-irradiation is composed of two
      phases. The early phase culminates with maximal levels of DNA binding ability at
      4 h postirradiation and is dependent on translational inhibition. The late-phase
      activation of NF-kappaB occurs between 16 and 48 h post-irradiation and the
      mechanism is not clear due to the fact that NF-kappaB was activated in the
      presence of high level of IkappaBalpha. In this report, we provide evidence that
      without translational inhibition, the transcription of IkappaBalpha was induced
      by UV-irradiation. In the late-phase of UV-induced NF-kappaB activation, the
      IkappaBalpha depletion is the combined result of regulation at both
      transcriptional and translational levels. Neither ubiquitination nor proteasomal
      degradation have detectable attributions to IkappaBalpha breakdown. We also
      demonstrate that UV only induced phosphorylation of p65(S276), while tumor
      necrosis factor-alpha induced phosphorylation at both Ser276 and 536 sites of
      p65. Based upon our results, we propose a novel mechanism for translation
      regulated IkappaBalpha depletion and MSK-mediated NF-kappaB activation at 24 h
      post-UV-irradiation.

PMID- 18627521
TI  - Fluorescence diagnosis of bladder cancer with new water soluble hypericin bound
      to polyvinylpyrrolidone: PVP-hypericin.
AB  - Although conventional white light endoscopy (WLE) is currently the gold standard
      for diagnosing bladder tumors, rates of false negative results and residual
      tumors after transurethral resection are relatively high. The goal of the present
      clinical study is to investigate whether using new water soluble hypericin (PVP
      hypericin) as a fluorescent dye improves bladder cancer detection and diagnosis.
      Following instillation of PVP-hypericin (total amount of 0.25 mg hypericin bound
      to 25 mg polyvinylpoyrrolidone [PVP], reconstituted in 50 mL phys. sodium
      chloride solution), WLE and fluorescence cystoscopy (photodynamic diagnosis; PDD)
      were performed on patients with suspected primary or recurrent bladder
      malignancies (n = 57). Incubation time was 1-2 h and biopsies (n = 163) were
      taken from fluorescing regions and/or from regions which were suspicious under
      WLE. Histological investigations of the biopsies provided the final proof of
      malignancy (or the counterevidence). Results indicated that overall sensitivity
      with PVP-hypericin and PDD is significantly higher (95%) than with WLE (85%). The
      sensitivity of PDD in the diagnosis of carcinoma in situ (n = 12) was 100%
      compared with 33% for WLE. In the diagnosis of dysplasia, the sensitivity of PDD
      was 85% compared with 31% for WLE. PDD has a positive predictive value (PPV) of
      0.75% and a negative predictive value (NPV) of 0.86%, in comparison to WLE PPV =
      0.66% NPV = 0.58%. Biopsies were not taken from healthy tissues, thus specificity
      was markedly lower in our study (53%) than that reported in other studies (98
      100%). As a conclusion, PDD using PVP-hypericin is superior to WLE in terms of
      sensitivity in the diagnosis of malignancies of the bladder. Results suggest that
      PVP-hypericin is a promising formulation for various diagnostic and therapeutic
      applications.

PMID- 18627522
TI  - Nondenatured soy extracts reduce UVB-induced skin damage via multiple mechanisms.
AB  - UV irradiation results in DNA damage, inflammation and immunosuppression, leading
      to the development of basal and squamous cell carcinomas. Earlier data show that
      topical treatment with nondenatured soy extracts reduced the incidence and
      delayed the development/progression of already-initiated skin tumors in high-risk
      hairless mice. Here we show that pretreatment with nondenatured soy extracts
      reduced UVB-induced Thymine-Thymine (TT) dimer formation. In vitro, nondenatured
      soy extracts enhanced UVB-induced checkpoint kinase-1 (Chk1) activation,
      suggesting a delay in cell cycle progression that enables longer time for DNA
      repair. Soy also reduced UVB-induced cyclo-oxygenase-2 (COX-2) expression and
      prostaglandin E2 secretion, and inhibited p38 MAP kinase activation, suggesting
      its anti-inflammatory activity. Mice pretreated topically with nondenatured soy
      extracts had reduced levels of UVB-induced TT dimers and COX-2 expression in
      their skins compared to UVB alone. The nondenatured soy extracts also inhibited
      vascular endothelial growth factor-induced endothelial tube formation in
      Matrigel, suggesting a possible inhibitory effect on angiogenesis and tumor
      progression. Taken together, nondenatured soy extracts could prevent or reduce
      UVB-induced skin damage via multiple mechanisms, affecting both the initiation
      and the progression of skin cancer. These data suggest that topical application
      of nondenatured soy extracts could potentially reduce the incidence of skin
      cancer.

PMID- 18627523
TI  - The photolysis of Chlorocarbonylbis(triphenylphosphine)iridium(I) in chloroform.
AB  - Under 254 or 313 nm irradiation in chloroform, [IrCl(CO)(PPh3)2] is converted
      cleanly to [IrCl2(CO)H(PPh3)2] through the addition of HCl, produced
      photochemically. Under 254 nm irradiation, some of the reaction of
      [IrCl(CO)(PPh3)2] occurs by direct photolysis of chloroform, though a greater
      contribution arises from a reaction initiated through absorption of light by the
      metal complex. Under 313 nm irradiation, essentially all of the reaction is metal
      initiated. The linear dependence of the reaction rate on light intensity and on
      the fraction of light absorbed by the Ir(I) complex as well as the lack of a
      deuterium isotope effect rule out a radical process. Instead it is proposed that
      an association complex between excited state [IrCl(CO)(PPh3)2] and CHCl3 leads to
      dissociation of a chlorine atom from CHCl3, yielding HCl after abstraction of a
      hydrogen from another CHCl3. HCl then adds to a ground state [IrCl(CO)(PPh3)2]
      complex.

PMID- 18627524
TI  - Photophysical properties of the prefluorescent nitroxide probes QT and C343T.
AB  - The photophysical properties of the nitroxide prefluorescent probes 4-(3-hydroxy
      2-methyl-4-quinolinoyloxy)-2,2,6,6-tetramethyl-piperidin-4-yl) ester free radical
      (QT) and 2,3,4,6,7,8-hexahydro-quinolizino [1,10,9-gh] coumarin-3-carboxylic acid
      (1-oxyl-2,2,6,6-tetramethyl-piperidin-4-yl) ester free radical (C343T) were
      evaluated as a function of pH and solvent properties. The absorbance of QT showed
      high pH sensitivity. The pKa values for the different ionization forms involved
      in the acid-base equilibrium of the quinoline chromophore were determined in the
      ground and excited states. The fluorescence lifetimes of QT, and N-hydroxylamine
      (QTH) and quinoline methyl ester (QMe) derivatives, showed that the
      intramolecular quenching efficiency by the nitroxide moiety is independent of the
      quinoline ionization form. The fluorescence and absorbance of C343T were highly
      sensitive to solvent polarity in agreement with a charged transfer excited state
      of the chromophore. However, we noted a decrease in the intramolecular
      fluorescence quenching efficiency by the nitroxide moiety when changing the
      polarity of the solvent from hexane to water. This behavior has been attributed
      to a suppression of an energy transfer mechanism in the nitroxide quenching
      process in very polar solvents. The results obtained in micelles allow us to
      propose QT and C343T as sensors for pH and micropolarity, respectively, in
      addition to their role as monitors for free radicals or hydrogen transfer from
      phenols.

PMID- 18627525
TI  - Neutrophil infiltration in normal human skin after exposure to different
      ultraviolet radiation sources.
AB  - Exposure of the skin to UV radiation can lead to a local infiltration of
      neutrophils. Not much is known on whether the infiltration of neutrophils in the
      irradiated skin is UV source dependent. In this study we compared different UV
      sources (solar-simulated radiation [SSR], narrowband [NB]-UVB, broadband [BB]-UVB
      and UVA1) in their potency to induce neutrophil infiltration in normal human skin
      after exposure to two times the minimal erythema dose of UV radiation. Biopsies
      were collected from irradiated buttock skin 6 and 24 h after irradiation and from
      nonirradiated skin. The presence, distribution and amount of skin-infiltrated
      neutrophils were determined using immunohistochemical staining. Analysis revealed
      that SSR was most effective in inducing neutrophil infiltration. NB-UVB gave a
      neutrophil influx pattern similar to that seen with SSR but in smaller numbers.
      BB-UVB and UVA1 were far less potent in inducing neutrophil infiltration compared
      with SSR or NB-UVB. Our findings indicate that neutrophil infiltration in the UV
      irradiated skin is UV source dependent. When the spectra emitted by the different
      UV sources were compared UVB seemed to be more effective than UVA in inducing
      neutrophil infiltration. Furthermore, our results suggest that longer wavelengths
      within the UVB range are mostly responsible for the infiltration of neutrophils
      in the UV-irradiated skin.

PMID- 18627526
TI  - A novel transport and delivery mechanism underpins the effectiveness of prolyl-m
      sarcolysyl-p-fluorophenylalanine (PSF) in a human melanoma xenograft nude-mouse
      model.
AB  - The alkylating peptide PSF shows very promising results in vitro on different
      cancer cells but its efficacy in animals has not been assessed. Here we evaluate
      the efficacy of PSF in human melanoma-bearing nude mice and examine the
      underlying mechanism. In melanoma-bearing nude mice, escalating doses of PSF
      showed dose-dependent responses and reached tumor regression with an optimal dose
      of 20 mg/kg for 1 month. A comparison of PSF with its free moiety m-sarcolysin
      and melphalan showed a highly significant advantage of PSF. Furthermore, dose
      fractionation yielded an even better control of tumor regrowth. In vitro studies
      unraveled an original delivery mechanism based on the rapid binding of PSF mainly
      due to red blood cells to form a pro-drug complex and the subsequent release of
      active metabolites by tumor-associated proteolytic enzymes. Blood kinetics showed
      one major metabolite partially released over time, while in the presence of
      melanoma cells three additional metabolites are generated. Interestingly, tumor
      shed proteases also induce the production of these metabolites and varying
      combinations of enzyme inhibitors indicate the involvement of metallo- and other
      families of proteases in the delivery process. This particular transport and
      delivery of such an alkylating agent may have several benefits, mainly lowering
      the drug-free moiety in plasma and at the same time increasing its concentration
      in protease rich areas such as tumors.

PMID- 18627527
TI  - Pigmentation effects of solar-simulated radiation as compared with UVA and UVB
      radiation.
AB  - Different wavelengths of ultraviolet (UV) radiation elicit different responses in
      the skin. UVA induces immediate tanning and persistent pigment darkening through
      oxidation of pre-existing melanin or melanogenic precursors, while UVB induces
      delayed tanning which takes several days or longer to develop and requires
      activation of melanocytes. We compared the effects of a 2-week repetitive
      exposure of human skin to solar-simulated radiation (SSR), UVA or UVB at doses
      eliciting comparable levels of visible tanning and measured levels of melanins
      and melanin-related metabolites. Levels of eumelanin and pheomelanin were
      significantly higher in the order of SSR, UVB, UVA or unexposed control skin.
      Levels of free 5-S-cysteinyldopa (5SCD) were elevated about 4-fold in SSR- or UVB
      exposed skin compared with UVA-exposed or control skin. Levels of protein-bound
      form of 5SCD tended to be higher in SSR- or UVB-exposed skin than in UVA-exposed
      or control skin. Total levels of 5-hydroxy-6-methoxyindole-2-carboxylic acid
      (5H6MI2C) and 6H5MI2C were higher in SSR- than in UVB-exposed or control skin.
      These results show that SSR is more effective in promoting delayed tanning than
      UVB radiation alone, suggesting a synergistic effect of UVA radiation.
      Furthermore, free 5SCD may serve as a good marker of the effect of SSR and UVB.

PMID- 18627528
TI  - Identification of novel epigenetically modified genes in human melanoma via
      promoter methylation gene profiling.
AB  - The inactivation of tumor-related genes through the aberrant methylation of
      promoter CpG islands is thought to contribute to tumor initiation and
      progression. We therefore investigated promoter methylation events involved in
      cutaneous melanoma by screening 30 genes of interest for evidence of promoter
      hypermethylation, examining 20 melanoma cell lines and 40 freshly procured
      melanoma samples. Utilizing quantitative methylation-specific PCR, we identified
      five genes (SOCS1, SOCS2, RAR-beta 2, TNFSF10C, and TNFSF10D) with
      hypermethylation frequencies ranging from 50% to 80% in melanoma cell lines as
      well as freshly procured tissue samples. Eighteen genes (LOX, RASSF1A, WFDC1, TM,
      APC, TFPI2, TNFSF10A, CDKN2A, MGMT, TIMP3, ASC, TPM1, IRF8, CIITA-PIV, CDH1, SYK,
      HOXB13, and DAPK1) were methylated at lower frequencies (2-30%). Two genes
      (CDKN1B and PTEN), previously reported as methylated in melanoma, and five other
      genes (RECK, IRF7, PAWR, TNFSF10B, and Rb) were not methylated in the samples
      screened here. Daughter melanoma cell lines showed identical methylation patterns
      when compared with original samples from which they were derived, as did
      synchronous metastatic lesions from the same patient. We identified four genes
      (TNFSF10C, TNFSF10D, LOX, and TPM1) that have never before been identified as
      hypermethylated in melanoma, with an overall methylation frequency of 60, 80, 50,
      and 10%, respectively, hypothesizing that these genes may play an important role
      in melanoma progression.

PMID- 18627529
TI  - The location of heart melanocytes is specified and the level of pigmentation in
      the heart may correlate with coat color.
AB  - Melanocytes are mainly found in the skin and more rarely in other parts of the
      body, including the heart. We analyzed the localization of heart melanocytes and
      their levels of pigmentation in a series of mutant mice presenting different
      numbers of melanocytes and pigmentation in the skin. We found that melanocytes
      were localized in the valves (mitral, tricuspid, and aortic) and septa
      (ventricular and atrial). Moreover, the numbers of melanocytes in the heart
      appears to reflect that of the skin. Mice having a high or low level of pigmented
      cells and/or melanin in valves and septa have similar lifespan. In this respect,
      melanocytes found in the valves and septa of the heart are probably not essential
      in a healthy and non-stressful environment.

PMID- 18627530
TI  - Pharmacologic suppression of MITF expression via HDAC inhibitors in the
      melanocyte lineage.
AB  - Melanoma incidence continues to rise at an alarming rate while effective systemic
      therapies remain very limited. Microphthalmia-associated transcription factor
      (MITF) is required for development of melanocytes and is an amplified oncogene in
      a fraction of human melanomas. Microphthalmia-associated transcription factor
      also plays an oncogenic role in human clear cell sarcomas, which typically
      exhibit melanoma-like features. Although pharmacologic suppression of MITF is of
      potential interest in a variety of clinical settings, it is not known to contain
      intrinsic catalytic activity capable of direct small molecule inhibition. An
      alternative drug-targeting strategy is to identify and interfere with lineage
      restricted mechanisms required for its expression. Here, we report that multiple
      histone deacetylase (HDAC)-inhibitor drugs potently suppress MITF expression in
      melanocytes, melanoma and clear cell sarcoma cells. Although HDAC inhibitors may
      affect numerous cellular targets, we observed suppression of skin pigmentation by
      topical drug application as well as evidence of anti-melanoma efficacy in vitro
      and in mouse xenografts. Consequently, HDAC inhibitor drugs are candidates to
      play therapeutic roles in targeting conditions affecting the melanocyte lineage.

PMID- 18627531
TI  - Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in
      melanocytes by ligands of the melanocortin 1 receptor.
AB  - The production of melanin in the hair and skin is tightly regulated by the
      melanocortin 1 receptor (MC1R) whose activation is controlled by two secreted
      ligands, alpha-melanocyte stimulating hormone (alphaMSH) and agouti signal
      protein (ASP). As melanin is extremely stable, lasting years in biological
      tissues, the mechanism underlying the relatively rapid decrease in visible
      pigmentation elicited by ASP is of obvious interest. In this study, the effects
      of ASP and alphaMSH on the regulation of melanin synthesis and on visible
      pigmentation were assessed in normal murine melanocytes and were compared with
      the quick depigmenting effect of the tyrosinase inhibitor, phenylthiourea (PTU).
      alphaMSH increased pheomelanin levels prior to increasing eumelanin content over
      4 days of treatment. Conversely, ASP switched off the pigment synthesis pathway,
      reducing eu- and pheo-melanin synthesis within 1 day of treatment that was
      proportional to the decrease in tyrosinase protein level and activity. These
      results demonstrate that the visible depigmentation of melanocytes induced by ASP
      does not require the degradation of existing melanin but rather is due to the
      dilution of existing melanin by melanocyte turnover, which emphasizes the
      importance of pigment distribution to visible color.

PMID- 18627532
TI  - A Cre::FLP fusion protein recombines FRT or loxP sites in transgenic maize
      plants.
AB  - SUMMARY: The coding sequences of Cre (site-specific recombinase from
      bacteriophage P1) and FLP (yeast 2-microm plasmid site-specific recombinase) were
      fused in frame to produce a novel, dual-function, site-specific recombinase gene.
      Transgenic maize plants containing the Cre::FLP fusion expression vector were
      crossed to transgenic plants containing either the loxP or FRT excision
      substrate. Complete and precise excisions of chromosomal fragments flanked by the
      respective target sites were observed in the F1 and F2 progeny plants. The
      episomal DNA recombination products were frequently lost. Non-recombined FRT
      substrates found in the F1 plants were recovered in the F2 generation after the
      Cre::FLP gene segregated out. They produced the recombination products in the F3
      generation when crossed back to the FLP-expressing plants. These observations may
      indicate that the efficiency of site-specific recombination is affected by the
      plant developmental stage, with site-specific recombination being more prevalent
      in developing embryos. The Cre::FLP fusion protein was also tested for excisions
      catalysed by Cre. Excisions were identified in the F1 plants and verified in the
      F2 plants by polymerase chain reaction and Southern blotting. Both components of
      the fusion protein (FLP and Cre) were functional and acted with similar
      efficiency. The crossing strategy proved to be suitable for the genetic
      engineering of maize using the FLP or Cre site-specific recombination system.

PMID- 18627533
TI  - Intramodal and crossmodal processing delays in the attentional blink paradigm
      revealed by event-related potentials.
AB  - In the attentional blink (AB), processing of a second target (T2) is impaired if
      it is presented shortly after the onset of a first target (T1), leading to a
      decrease in accurate report of T2 if T2 is masked. Some prominent theories of the
      AB suggest that an amodal bottleneck in working memory consolidation underlies
      the AB. We investigated this by factorially manipulating T1 and T2 modalities
      (visual or auditory) using equivalent stimuli and tasks in both modalities to
      minimize task switching. T2 was not masked. In all modality combinations, the
      electrophysiological P3 component to T2, obtained by subtracting T1 only trials
      from T1+T2 trials, was delayed and reduced in amplitude when T2 was presented
      soon after T1 relative to when T1 and T2 were presented farther apart. Results
      provide support for a common amodal bottleneck that underlies the AB effects
      observed in all visual/auditory modality combinations.

PMID- 18627535
TI  - The effects of achievement motivation, task difficulty, and goal difficulty on
      physiological, behavioral, and subjective effort.
AB  - The purpose of the study was to present experimental arguments evaluating the
      Humphreys and Revelle's model of effort. Two important factors were tested:
      achievement motivation and difficulty. Heart rate, heart rate variability, blood
      pressure, facial electromyographic reactivity, and reaction time were measured as
      an index of effort expenditure. A 2x2x2 factorial design was used with two levels
      of resultant achievement motivation, two levels of task difficulty, and two
      levels of goal difficulty. As expected, the 16 participants high in resultant
      achievement motivation showed a better performance and had a larger decrease of
      the midfrequency band than the 16 participants low in resultant achievement
      motivation, especially during the difficult task. Results lend some support for
      the impact of resultant achievement motivation, task difficulty, and goal
      difficulty on effort mobilization.

PMID- 18627536
TI  - Deficits in early emotional reactivity in alexithymia.
AB  - Alexithymia is characterized by a difficulty in identifying and describing one's
      emotions. This study addressed the question of whether alexithymic tendencies are
      related to limited affective reactivity to briefly presented emotional stimuli.
      Skin conductance responses were assessed and backward masking was used to
      minimize elaborated processing of emotional pictures. Results indicated that
      alexithymic tendencies are associated with smaller electrodermal responses to
      briefly presented negative pictures. These effects were driven by difficulties in
      identifying and communicating emotions whereas externally orientated thinking was
      unrelated to affective reactivity. We conclude that there is an early processing
      deficit in response to negative stimuli in participants with high scores in
      alexithymia. Differences in the early emotional reactivity to arousing material
      could contribute to difficulties in emotional processes related to alexithymia.

PMID- 18627534
TI  - Neuroanatomical correlates of aging, cardiopulmonary fitness level, and
      education.
AB  - Fitness and education may protect against cognitive impairments in aging. They
      may also counteract age-related structural changes within the brain. Here we
      analyzed volumetric differences in cerebrospinal fluid and gray and white matter,
      along with neuropsychological data, in adults differing in age, fitness, and
      education. Cognitive performance was correlated with fitness and education. Voxel
      based morphometry was used for a whole-brain analysis of structural magnetic
      resonance images. We found age-related losses in gray and white matter in medial
      temporal, parietal, and frontal areas. As in previous work, fitness within the
      old correlated with preserved gray matter in the same areas. In contrast, higher
      education predicted preserved white matter in inferior frontal areas. These data
      suggest that fitness and education may both be predictive of preserved cognitive
      function in aging through separable effects on brain structure.

PMID- 18627537
TI  - Analysis of local acceptance of a radioactive waste disposal facility.
AB  - Like many other countries in the world, Korea has struggled to site a facility
      for radioactive waste for almost 30 years because of the strong opposition from
      local residents. Finally, in 2005, Gyeongju was established as the first Korean
      site for a radioactive waste facility. The objectives of this research are to
      verify Gyeongju citizens' average level of risk perception of a radioactive waste
      disposal facility as compared to other risks, and to explore the best model for
      predicting respondents' acceptance level using variables related to cost-benefit,
      risk perception, and political process. For this purpose, a survey is conducted
      among Gyeongju residents, the results of which are as follows. First, the local
      residents' risk perception of an accident in a radioactive waste disposal
      facility is ranked seventh among a total of 13 risks, which implies that nuclear
      related risk is not perceived very highly by Gyeongju residents; however, its
      characteristics are still somewhat negative. Second, the comparative regression
      analyses show that the cost-benefit and political process models are more
      suitable for explaining the respondents' level of acceptance than the risk
      perception model. This may be the result of the current economic depression in
      Gyeongju, residents' familiarity with the nuclear industry, or cultural
      characteristics of risk tolerance.

PMID- 18627538
TI  - Trust in the safety of tourist destinations: hard to gain, easy to lose? New
      insights on the asymmetry principle.
AB  - According to the asymmetry principle of trust, negative events decrease trust to
      a much higher extent than positive events increase trust. The study at hand
      intended to verify whether this notion of asymmetry holds true with respect to
      trust in the safety of tourist destinations. Thus, in contrast to previous
      research that analyzed trust asymmetry in the context of involuntary
      technological risks, the present study evaluates the validity of the asymmetry
      principle of trust in the context of voluntary tourism risks. The hypothesis that
      negative or risky information on destination safety (absence of proper safety
      measures and conditions) has a higher impact on distrust than, conversely,
      positive or nonrisk information on destination safety (provision of proper safety
      measures and conditions) has on trust was tested in an online survey (N= 640). In
      contrast to the asymmetry pattern found by Slovic (1993), results of the current
      work suggest symmetry rather than asymmetry of trust. The presence of proper
      safety measures and conditions (positive or nonrisk information) was found to
      have at least the same-and in some cases an even higher-impact on trust than the
      absence of such measures and conditions (negative or risky information) had on
      distrust. Findings provide empirical evidence for the thesis that the prevalence
      of trust asymmetry is dependent on the risk source and demonstrate that trust is
      symmetric rather than asymmetric in the context of voluntary tourism risks.
      Furthermore, results imply an influence of positive versus negative expectations
      as well as of prior trusting relationships on the occurrence of the asymmetry
      principle.

PMID- 18627539
TI  - Current definitions of risk for food safety and animal health allow risk
      assessments to provide substantially different outcomes.

PMID- 18627540
TI  - A sensitivity analysis of the social vulnerability index.
AB  - The Social Vulnerability Index (SoVI), created by Cutter et al. (2003), examined
      the spatial patterns of social vulnerability to natural hazards at the county
      level in the United States in order to describe and understand the social burdens
      of risk. The purpose of this article is to examine the sensitivity of
      quantitative features underlying the SoVI approach to changes in its
      construction, the scale at which it is applied, the set of variables used, and to
      various geographic contexts. First, the SoVI was calculated for multiple
      aggregation levels in the State of South Carolina and with a subset of the
      original variables to determine the impact of scalar and variable changes on
      index construction. Second, to test the sensitivity of the algorithm to changes
      in construction, and to determine if that sensitivity was constant in various
      geographic contexts, census data were collected at a submetropolitan level for
      three study sites: Charleston, SC; Los Angeles, CA; and New Orleans, LA. Fifty
      four unique variations of the SoVI were calculated for each study area and
      evaluated using factorial analysis. These results were then compared across study
      areas to evaluate the impact of changing geographic context. While decreases in
      the scale of aggregation were found to result in decreases in the variance
      explained by principal components analysis (PCA), and in increases in the
      variance of the resulting index values, the subjective interpretations yielded
      from the SoVI remained fairly stable. The algorithm's sensitivity to certain
      changes in index construction differed somewhat among the study areas.
      Understanding the impacts of changes in index construction and scale are crucial
      in increasing user confidence in metrics designed to represent the extremely
      complex phenomenon of social vulnerability.

PMID- 18627541
TI  - An exploratory risk perception study of attitudes toward homeland security
      systems.
AB  - Understanding the issues surrounding public acceptance of homeland security
      systems is important for balancing security needs and potential civil liberties
      infringements. A psychometric survey was used in an exploratory study of
      attitudes regarding homeland security systems. Psychometric rating data were
      obtained from 182 respondents on psychological attributes associated with 12
      distinct types of homeland security systems. An inverse relationship was observed
      for the overall rating attributes of acceptability and risk of civil liberties
      infringement. Principal components analysis (PCA) yielded a two-factor solution
      with the rating scale loading pattern suggesting factors of perceived
      effectiveness and perceived intrusiveness. These factors also showed an inverse
      relationship. The 12 different homeland security systems showed significantly
      different scores on the rating scales and PCA factors. Of the 12 systems studied,
      airport screening, canine detectors, and radiation monitoring at borders were
      found to be the most acceptable, while email monitoring, data mining, and global
      positioning satellite (GPS) tracking were found to be least acceptable. Students
      rated several systems as more effective than professionals, but the overall
      pattern of results for both types of subjects was similar. The data suggest that
      risk perception research and the psychometric paradigm are useful approaches for
      quantifying attitudes regarding homeland security systems and policies and can be
      used to anticipate potentially significant public acceptance issues.

PMID- 18627542
TI  - Explosion probability of unexploded ordnance: expert beliefs.
AB  - This article reports on a study to quantify expert beliefs about the explosion
      probability of unexploded ordnance (UXO). Some 1,976 sites at closed military
      bases in the United States are contaminated with UXO and are slated for cleanup,
      at an estimated cost of $15-140 billion. Because no available technology can
      guarantee 100% removal of UXO, information about explosion probability is needed
      to assess the residual risks of civilian reuse of closed military bases and to
      make decisions about how much to invest in cleanup. This study elicited
      probability distributions for the chance of UXO explosion from 25 experts in
      explosive ordnance disposal, all of whom have had field experience in UXO
      identification and deactivation. The study considered six different scenarios:
      three different types of UXO handled in two different ways (one involving
      children and the other involving construction workers). We also asked the experts
      to rank by sensitivity to explosion 20 different kinds of UXO found at a case
      study site at Fort Ord, California. We found that the experts do not agree about
      the probability of UXO explosion, with significant differences among experts in
      their mean estimates of explosion probabilities and in the amount of uncertainty
      that they express in their estimates. In three of the six scenarios, the
      divergence was so great that the average of all the expert probability
      distributions was statistically indistinguishable from a uniform (0, 1)
      distribution-suggesting that the sum of expert opinion provides no information at
      all about the explosion risk. The experts' opinions on the relative sensitivity
      to explosion of the 20 UXO items also diverged. The average correlation between
      rankings of any pair of experts was 0.41, which, statistically, is barely
      significant (p= 0.049) at the 95% confidence level. Thus, one expert's rankings
      provide little predictive information about another's rankings. The lack of
      consensus among experts suggests that empirical studies are needed to better
      understand the explosion risks of UXO.

PMID- 18627543
TI  - Risk perceptions, optimism, and natural hazards.
AB  - This article uses the panel survey developed for the Health and Retirement Study
      to evaluate whether Hurricane Andrew in 1992 altered longevity expectations of
      respondents who lived in Dade County, Florida, the location experiencing the
      majority of about 20 billion dollars of damage. Longevity expectations have been
      used as a proxy measure for both individual subjective risk assessments and
      dispositional optimism. The panel structure allows comparison of those
      respondents' longevity assessments when the timing of their survey responses
      bracket Andrew with those of individuals where it does not. After controlling for
      health effects, the results indicate a significant reduction in longevity
      expectations due to the information respondents appear to have associated with
      the storm.

PMID- 18627544
TI  - Uncertainty and sensitivity analyses of a decision analytic model for
      posteradication polio risk management.
AB  - Decision analytic modeling of polio risk management policies after eradication
      may help inform decisionmakers about the quantitative tradeoffs implied by
      various options. Given the significant dynamic complexity and uncertainty
      involving posteradication decisions, this article aims to clarify the structure
      of a decision analytic model developed to help characterize the risks, costs, and
      benefits of various options for polio risk management after eradication of wild
      polioviruses and analyze the implications of different sources of uncertainty. We
      provide an influence diagram of the model with a description of each component,
      explore the impact of different assumptions about model inputs, and present
      probability distributions of model outputs. The results show that choices made
      about surveillance, response, and containment for different income groups and
      immunization policies play a major role in the expected final costs and polio
      cases. While the overall policy implications of the model remain robust to the
      variations of assumptions and input uncertainty we considered, the analyses
      suggest the need for policymakers to carefully consider tradeoffs and for further
      studies to address the most important knowledge gaps.

PMID- 18627545
TI  - Communicating risks and benefits from fish consumption: impact on Belgian
      consumers' perception and intention to eat fish.
AB  - Communicating about the health effects of fish and seafood may potentially result
      in a conflict situation: increasing intake is desirable because of health and
      nutritional benefits, but higher consumption may also lead to an increased intake
      of potentially harmful environmental contaminants. In order to anticipate the
      communication challenge this conflict may pose, the research presented here aimed
      to assess the impact of risk/benefit communication on Belgian consumers' fish
      consumption behavior and fish attribute perception. Data were collected in June
      2005 from a sample of 381 women, aged between 20 and 50 years. An experimental
      design consisting of four message conditions (benefit-only; risk-only; benefit
      risk; and risk-benefit) combined with three information sources (fish and food
      industry; consumer organization; government) was used. Exposure to the benefit
      only message resulted in an increase from a self-reported fish consumption
      frequency of 4.2 times per month to an intended fish consumption frequency of 5.1
      times per month (+21%), while fish attribute perceptions only marginally
      improved. The risk-only message resulted in a strong negative perceptual change
      in the range of two points on a seven-point scale. This translated into an 8%
      decrease of behavioral intention (from eating fish 4.5 times per month to an
      intention of eating fish 4.1 times per month). Balanced messages referring to
      both risks and benefits yielded no significant change in behavioral intention,
      despite a significant worsening of fish attribute perception. The presentation
      order of benefits and risks in the balanced message showed a tendency to affect
      both behavioral intention and attribute perception, with the first message
      component being most influential. Information source did not yield any
      significant impact either on behavioral intention or on attribute perceptions,
      independent of the message content. The results from this study provide valuable
      insights for future risk/benefit and balanced communication about seafood.

PMID- 18627546
TI  - The lost value of groundwater and its influence on environmental decision making.
AB  - A critical aspect in establishing environmental policies lies in the proper
      assessment of the value of the resource being affected. Standard risk assessment
      analyses calculate the cost of pollution as consisting, solely, of the cost to
      remediate a site. This traditional definition is extended here to include the
      lost value of groundwater. These concepts and their impact on decision-making
      analyses are illustrated through the case of municipal waste landfills. Based on
      data from existing polluting sites, a simple cost-benefit probabilistic analysis
      is conducted first, which equates, as is the practice, the cost of pollution to
      that of remediation. This leads rationally to selection of the lowest-protection
      technology. Using plausible arguments the reduction in value of groundwater from
      potable high-quality water to irrigation water, which is what is returned after
      remediation, is argued. The arguments consist of: (a) the ratio of the subsidized
      prices of drinking to irrigation water reflects the relative value of the use of
      water; (b) the amount paid for remediation, in each case, represents, at a
      minimum, the value of the water recovered; and (c) the lost value of groundwater
      equals the value of drinking water minus the value of irrigation water.
      Incorporation of this lost value of groundwater is sufficient to drastically
      alter the conclusions of the decision-making analysis and make the highest level
      technology the most rational and profitable alternative. The broader point of
      this article lies in that proper accounting of environmental costs is necessary
      in order to alter environmental policies and practices.

PMID- 18627547
TI  - Upstream oversight assessment for agrifood nanotechnology: a case studies
      approach.
AB  - Although nanotechnology is broadly receiving attention in public and academic
      circles, oversight issues associated with applications for agriculture and food
      remain largely unexplored. Agrifood nanotechnology is at a critical stage in
      which informed analysis can help shape funding priorities, risk assessment, and
      oversight activities. This analysis is designed to help society and policymakers
      anticipate and prepare for challenges posed by complicated, convergent
      applications of agrifood nanotechnology. The goal is to identify data, risk
      assessment, regulatory policy, and engagement needs for overseeing these products
      so they can be addressed prior to market entry. Our approach, termed upstream
      oversight assessment (UOA), has potential as a key element of anticipatory
      governance. It relies on distinct case studies of proposed applications of
      agrifood nanotechnology to highlight areas that need study and attention. As a
      tool for preparation, UOA anticipates the types and features of emerging
      applications; their endpoints of use in society; the extent to which users,
      workers, ecosystems, or consumers will be exposed; the nature of the material and
      its safety; whether and where the technologies might fit into current regulatory
      system(s); the strengths and weaknesses of the system(s) in light of these novel
      applications; and the possible social concerns related to oversight for them.

PMID- 18627548
TI  - A method for computing the fraction of attributable risk related to climate
      damages.
AB  - The recent decision of the U.S. Supreme Court on the regulation of CO2 emissions
      from new motor vehicles shows the need for a robust methodology to evaluate the
      fraction of attributable risk from such emissions. The methodology must enable
      decisionmakers to reach practically relevant conclusions on the basis of expert
      assessments the decisionmakers see as an expression of research in progress,
      rather than as knowledge consolidated beyond any reasonable doubt. This article
      presents such a methodology and demonstrates its use for the Alpine heat wave of
      2003. In a Bayesian setting, different expert assessments on temperature trends
      and volatility can be formalized as probability distributions, with initial
      weights (priors) attached to them. By Bayesian learning, these weights can be
      adjusted in the light of data. The fraction of heat wave risk attributable to
      anthropogenic climate change can then be computed from the posterior
      distribution. We show that very different priors consistently lead to the result
      that anthropogenic climate change has contributed more than 90% to the
      probability of the Alpine summer heat wave in 2003. The present method can be
      extended to a wide range of applications where conclusions must be drawn from
      divergent assessments under uncertainty.

PMID- 18627549
TI  - Effect of specific colostral antibodies and selected lactobacilli on the adhesion
      of Helicobacter pylori on AGS cells and the Helicobacter-induced IL-8 production.
AB  - Helicobacter pylori infection is the most common cause of gastritis, gastric
      ulcer and adenocarcinoma. It has proven difficult to cure because of its
      capability to develop strains resistant to antibiotics. The effect of three
      strains of lactic acid bacteria (LAB) and bovine colostral preparations on the
      adhesion of H. pylori NCTC 11637 on gastric adenocarcinoma (AGS) cells and on the
      interleukin (IL)-8 production was studied. Before infection, H. pylori were
      pretreated with Lactobacillus plantarum MLBPL1, Lactobacillus rhamnosus GG,
      Lactococcus lactis, or with a colostral preparation with or without specific H.
      pylori antibodies. The relative number of H. pylori adhered on AGS cells was
      determined by urease test. IL-8 produced by the cells was studied by enzyme
      linked immunosorbent assay. Colostral preparations with and without specific
      antibodies reduced the adhesion of H. pylori on AGS cells in a dose-dependent
      manner. Live LAB at a concentration of 10(10) CFU/ml reduced the adhesion by
      approximately 50% (P < 0.05). After the infection of AGS cells by H. pylori, the
      IL-8 level rose up to about 10-fold (5500 +/- 1600 pg/ml). Pretreatment of H.
      pylori with colostral preparations or high concentrations of LAB prevented this
      IL-8 rise. Similar effect was seen with live and heat-killed LAB, the live LAB
      being more effective. Heat-killed LAB at a concentration of 10(10) CFU/ml rose
      the IL-8 level of non-infected cells significantly. Suppression of IL-8
      production by LAB or colostral products could have a suppressive effect on
      inflammation in Helicobacter infection.

PMID- 18627550
TI  - Correlates of regular exercise during pregnancy: the Norwegian Mother and Child
      Cohort Study.
AB  - The aims of this study were to describe the level of exercise during pregnancy
      and to assess factors associated with regular exercise. Using data from the
      Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of
      Public Health, 34 508 pregnancies were included in the present study. Data were
      collected by self-completed questionnaires in gestational weeks 17 and 30, and
      analyzed by logistic regression analysis. The results are presented as adjusted
      odds ratios (aOR) with a 95% confidence interval. The proportion of women
      exercising regularly was 46.4% before pregnancy and decreased to 28.0 and 20.4%
      in weeks 17 and 30, respectively. Walking and bicycling were the most frequently
      reported activities before and during pregnancy. The prevalence of swimming
      tended to increase from prepregnancy to week 30. Exercising regularly
      prepregnancy was highly related to regular exercise in week 17, aOR=18.4 (17.1
      19.7) and 30, aOR 4.3 (4.1-4.6). Low gestational weight gain was positively
      associated with regular exercise in week 30, aOR=1.2 (1.1-1.4), whereas being
      overweight before pregnancy was inversely associated with regular exercise in
      week 17, aOR=0.8 (0.7-0.8) and 30, aOR=0.7 (0.6-0.7). Also, women experiencing a
      multiple pregnancy, pelvic girdle pain, or nausea were less likely to exercise
      regularly.

PMID- 18627551
TI  - Influences of competition level, gender, player nationality, career stage and
      playing position on relative age effects.
AB  - Relative age, referring to the chronological age differences between individuals
      within annually age-grouped cohorts, is regarded as influential to an athlete's
      development, constraining athletic skill acquisition. While many studies have
      suggested different mechanisms for this effect, they have typically examined
      varying sports, precluding an examination of the possible inter-play between
      factors. Our three studies try to bridge this gap by investigating several
      moderators for relative age effects (RAEs) in one sport. Handball is a sport with
      position-specific demands, high cultural relevance and a performance context with
      established developmental structures and levels of representation for males and
      females. In Study 1, we investigated the influence of competition level and
      gender on RAEs before adulthood. In Study 2, elite participation, player
      nationality and stage of career are considered during adulthood. In Study 3,
      playing position and laterality (i.e., right vs left handedness) are investigated
      as moderators. Collectively, the results emphasize the complex inter-play of
      direct and indirect influences on RAEs in sports, providing evidence toward
      explaining how RAEs influence the development and maintenance of expertise.

PMID- 18627552
TI  - Longitudinal changes in genetic and environmental influences on older women's
      walking ability.
AB  - This study examined the stability and change over time in genetic and
      environmental influences on walking ability among older women. Maximal walking
      speed over 10 m and 6-min walking endurance test were measured under standard
      conditions at baseline and 3 years later. At both times, 63 monozygotic (MZ) and
      67 dizygotic (DZ) twin pairs were measured for walking speed and 58 MZ and 56 DZ
      pairs for walking endurance. Participants were twin sisters reared together and
      aged 63-75 years at baseline. Genetic and environmental influences were examined
      using longitudinal genetic modelling. The results showed that walking speed was
      preserved from baseline to follow-up. Genetic influences on walking speed were
      also similar at baseline (56%) and follow-up (60%). Walking endurance declined
      from baseline to follow-up, while genetic influences for walking endurance
      increased from baseline (40%) to follow-up (60%). Most of the genetic influences
      identified at baseline were also present at follow-up for walking speed
      (r(g)=0.72) and endurance (r(g)=0.71). In conclusion, among relatively healthy
      older women, genetic influences on walking speed and endurance were moderate at
      baseline, while at 3-year follow-up a moderate increment was observed in walking
      endurance. Newly expressed genetic influences were recognized at follow-up.

PMID- 18627553
TI  - Inflammatory factors, physical activity, and physical fitness in young people.
AB  - Cardiovascular disease (CVD) remains one of the leading causes of morbidity and
      mortality in developed countries. Over the past decade there has been much focus
      on the role of inflammation in the pathogenesis of atherosclerosis; to this end,
      there is increasing research on inflammatory factors such as C-reactive protein
      (CRP), interleukin-6 (IL-6), and fibrinogen (Fg). There is compelling evidence
      that physical activity (PA) and physical fitness (PF) protect against chronic
      disease. More recently, research has shown that exercise reduces CRP, IL-6, and
      Fg concentration in adults, and that this is often independent of adiposity.
      Although there are some data to suggest that this is similarly true for young
      people, there is inconsistency in the literature. The following review aims to
      illustrate what is known about the effects of PA and PF on inflammatory factors
      in young people aged 5-18 years.

PMID- 18627554
TI  - Effect of acute hypoxia on central fatigue during repeated isometric leg
      contractions.
AB  - To determine whether hypoxia has a direct influence on the central command
      independently of the working muscles, 16 subjects performed intermittent
      isometric unilateral knee extensions until exhaustion either in normobaric
      hypoxia (inspired O(2) fraction=0.11, arterial oxygen saturation approximately
      84%) or in normoxia while the knee extensor muscles were exposed to circulatory
      occlusion with a 250 mmHg cuff. Among the subjects, 11 also performed the tests
      in hypoxia and normoxia without occlusion. Single electrical stimulations were
      regularly delivered to the femoral nerve to measure the changes in the knee
      extensor peak twitch force. With the cuff, the average slope of decrease in peak
      twitch did not depend on the inspired oxygen fraction. Performance was slightly
      but significantly lower during hypoxia than in normoxia (8.2+/-2.6 vs 9.4+/-3.1
      repetitions, P<0.05) with the cuff on. The number of repetitions was much higher
      during hypoxia with maintaining leg blood flow (15.6+/-4.5 repetitions) than with
      circulatory occlusion in normoxia. In conclusion, this study showed that a direct
      effect of hypoxia in reducing the motor drive to the working muscles exists but
      this effect is moderate.

PMID- 18627555
TI  - Cross-sectional investigation of indices of isokinetic leg strength in youth
      soccer players and untrained individuals.
AB  - In this cross-sectional study, the differences in the isokinetic peak torque of
      the knee joint muscles (dominant and non-dominant) were investigated in three
      groups of youths (n=45; age, 14.9+/-1.1 years) with different soccer training
      backgrounds. Significant main effects were observed for training background on
      the functional hamstrings to quadriceps ratios for knee flexion (H(CON):Q(ECC)
      ratio; F(2,42)=4.023, P=0.025) and extension (H(ECC):Q(CON) ratio; F(2,42)=8.53,
      P<0.001) at 4.32 rad/s. Post hoc tests indicated that both ratios were
      significantly different between conventionally trained players compared with
      resistance-trained players and controls (mean+/-SD; H(ECC):Q(CON) ratio, dominant
      limb; 0.91+/-0.10; 1.04+/-0.12; 1.10+/-0.22; non-dominant limb; 0.89+/-0.09;
      1.05+/-0.19; 1.06+/-0.15; H(CON):Q(ECC) ratio, dominant limb; 0.36+/-0.06; 0.34+/
      0.07; 0.30+/-0.08; non-dominant limb; 0.33+/-0.05; 0.32+/-0.08; 0.28+/-0.07).
      Results suggest that the muscle-loading patterns experienced in youth soccer may
      alter the reciprocal balance of strength about the knee under high-velocity
      conditions. The findings also indicate that these balances may be improved by
      incorporating resistance training into the habitual exercise routines of youth
      soccer players.

PMID- 18627556
TI  - Dieting and disordered eating in German high school athletes and non-athletes.
AB  - The purpose of this study was to examine weight concerns, dieting, body
      dissatisfaction as well as eating behavior of German high school athletes and to
      compare disordered eating behavior of these athletes with regular high school
      students. Five hundred and seventy-six young athletes of Elite Sports Schools in
      the German state of Thuringia and a reference group consisting of 291 non
      athletes from regular high schools completed a questionnaire regarding eating
      behavior and attitudes, dietary history, body image and demographics. The Eating
      Attitude Test was used to measure disordered eating. Athletes did not show a
      higher frequency of disordered eating than non-athletes. A binary logistic
      regression analysis revealed that gender and dietary experience, but not group
      (athletes vs non-athletes), were significant predictors of disordered eating. It
      can be concluded that dietary experience and female gender proved to be important
      risk factors of disordered eating. Participation in sports seems to be protective
      for developing serious eating problems, especially in girls. Potentially, regular
      monitoring of athletic performance by coaches might be a reason for this finding.

PMID- 18627557
TI  - Does a physical activity referral scheme improve the physical activity among
      routine primary health care patients?
AB  - Physical activity referral (PAR) schemes or concepts occur in varying forms.
      Because few physical activity intervention studies have been carried out in
      routine health care settings, it is difficult to translate research findings into
      daily practice. The aim of this study was to analyze the effectiveness of a PAR
      scheme implemented in routine primary health care. The study did not include a
      control group and was based on the ordinary staff's work efforts and follow-up
      measures. During a 2-year period, 6300 PARs were issued. Effectiveness was
      measured by an increase in self-reported physical activity. Half of the patients
      reached reported increased physical activity both at 3 months (49%) and at 12
      months (52%). The proportion of inactive patients decreased from 33% at baseline
      to 17% at 3 months and 20% at 12 months. The proportion of patients who were
      physically active on a regular basis increased from 22% at baseline to 33% at 3
      months and 32% at 12 months. Neither the patient's age nor the profession of the
      prescriber was associated with differences in effectiveness. The patient's
      activity level at baseline, the type of physical activity as well as the reason
      for the prescription were associated with increased physical activity.

PMID- 18627558
TI  - Pilot study of female high school basketball players' anterior cruciate ligament
      injury knowledge, attitudes, and practices.
AB  - An anterior cruciate ligament (ACL) injury prevention program was evaluated. One
      hundred and thirteen female high school varsity and junior varsity basketball
      players and 12 coaches participated in an 8-week educational and skills program.
      Demographic and injury history data were collected. At pre-intervention and at
      the end of season, knowledge, attitudes, and practices about ACL risk and injury
      prevention were assessed via questionnaires, and frequency of two-footed landings
      were videotaped during games. Univariate statistics described the sample. Paired
      t-tests evaluated the program's impact. Cronbach's alpha, correlations, and kappa
      statistics assessed the validity and reliability of questionnaires and video
      analysis. Of the 113 players, 74 completed the study. The players' mean age was
      16.25 years (SD=1.07; range=14.2-18.8). Baseline knowledge score was 57.2%,
      practice 58.4%, and attitude 73.5%. The mean baseline knowledge score of the 12
      coaches (mean age=40.8 years; SD=10.3; range=26.9-56.3) was 68.7%. Players'
      knowledge about ACL injury prevention improved (t=2.57; P<0.01). No changes in
      attitudes toward injury prevention were found (t(diff)=1.88; P<0.06). Inter-rater
      reliability of two-footed landings observed was acceptable (kappa=0.72).
      Videotape analyses revealed a 5.5% increase in landing performance (t(diff)=9.6;
      P<0.0001). The program increased knowledge about ACL injury risk and improved
      player's landing skills.

PMID- 18627559
TI  - Effect of proprioceptive neuromuscular facilitation stretching on the plantar
      flexor muscle-tendon tissue properties.
AB  - Proprioceptive neuromuscular facilitation (PNF) stretching programs have been
      shown to be the most effective stretching technique to increase the range of
      motion (ROM). The objective of this study was to examine the mechanism of effect
      of PNF stretching on changes in the ROM. Sixty-two healthy subjects were
      randomized into two groups: a PNF stretching group and a control group. The PNF
      group performed a 6-week stretching program for the calf muscles. Before and
      after this period, all subjects were evaluated for dorsiflexion ROM, passive
      resistive torque (PRT) of the plantar flexors and stiffness of the Achilles
      tendon. The results of the study revealed that the dorsiflexion ROM was
      significantly increased in the PNF group (DeltaROMext: 5.97+/-0.671 degrees ;
      DeltaROMflex: 5.697+/-0.788 degrees ). The PRT of the plantar flexors and the
      stiffness of the Achilles tendon did not change significantly after 6 weeks of
      PNF stretching. These findings provide evidence that PNF stretching results in an
      increased ankle dorsiflexion. However, this increase in ROM could not be
      explained by a decrease of the PRT or by a change in stiffness of the Achilles
      tendon, and therefore can be explained by an increase in stretch tolerance.

PMID- 18627560
TI  - Heterogeneous recruitment of quadriceps muscle portions and fibre types during
      moderate intensity knee-extensor exercise: effect of thigh occlusion.
AB  - The involvement of quadriceps femoris muscle portions and fibre type recruitment
      was studied during submaximal knee-extensor exercise without and with thigh
      occlusion (OCC) and compared with responses during intense exercise. Six healthy
      male subjects performed 90-s of moderate exercise without (MOD; 29+/-4 W) and
      with thigh OCC, and moderate exercise followed by 90-s of intense exercise (HI;
      65+/-8 W). Temperatures were continuously measured in m. vastus lateralis (VL),
      vastus medialis (VM) and rectus femoris (RF) and successive muscle biopsies were
      obtained from VL. During MOD, muscle temperature increase (DeltaT(m)) in RF was
      0.52+/-0.09 degrees C, which was 57% and 73% higher (P<0.05) than in VL and VM,
      respectively. During OCC, DeltaT(m) in RF was 0.39+/-0.05 degrees C, which was
      not different from VM but 54% higher (P<0.05) than in VL. After MOD, muscle CP in
      slow twitch (ST) and fast twitch (FT) fibres was 81% and 91% of resting levels,
      respectively, with lower (P<0.05) values after OCC (15% and 22%) and HI (24% and
      13%). After MOD, OCC and HI, a total of 48%, 93% and 96% of the ST fibres had CP
      levels below mean-1 SD, respectively, with corresponding values for FT fibres
      being 41%, 89% and 100%, respectively. In conclusion, a heterogeneous recruitment
      of the quadriceps muscle portions and muscle fibres was observed during
      submaximal knee-extensor exercise, whereas recruitment pattern was homogenous
      during intense exercise. Thigh OCC caused an altered recruitment of fibres and
      muscle portions, suggesting a significant afferent response affecting the
      activation of fibres in the contracting muscles.

PMID- 18627561
TI  - Acute effects of passive stretching vs vibration on the neuromuscular function of
      the plantar flexors.
AB  - This study examined the acute effects of passive stretching (PS) vs prolonged
      vibration (VIB) on voluntary peak torque (PT), percent voluntary activation
      (%VA), peak twitch torque (PTT), passive range of motion (PROM), musculotendinous
      stiffness (MTS), and surface electromyographic (EMG) and mechanomyographic (MMG)
      amplitude of the medial gastrocnemius (MG) and soleus (SOL) muscles during
      isometric maximal voluntary contractions (MVCs) of the plantar flexors. Fifteen
      healthy men performed the isometric MVCs and PROM assessments before and after 20
      min of PS, VIB, and a control (CON) conditions. There were 10% and 5% decreases
      in voluntary PT, non-significant 3% and 2% decreases in %VA, 9-23% decreases in
      EMG amplitude of the MG and SOL after the PS and VIB, respectively, with no
      changes after the CON. PROM increased by 19% and MTS decreased by 38% after the
      PS, but neither changed after the VIB or CON conditions. Both PS and VIB elicited
      similar neural deficits (i.e., gamma loop impairment) that may have been
      responsible for the strength losses. However, mechanical factors related to PROM
      and MTS cannot be ruled out as contributors to the stretching-induced force
      deficit.

PMID- 18627564
TI  - Secondary arteriovenous fistulas: converting prosthetic AV grafts to autogenous
      dialysis access.
AB  - As existing arteriovenous grafts (AVGs) fail, the National Kidney Foundation
      KDOQI Guidelines and the AV Fistula First Breakthrough Initiative ("Fistula
      First") project recommend that each patient be re-evaluated for conversion to an
      arteriovenous fistula (AVF). AVFs created following failure of an AVG have been
      termed secondary fistulas (SAVF). We review our experience and outcomes
      converting AVGs to SAVFs, utilizing the mature outflow vein of the AVG when
      possible, otherwise creating a new AVF at a remote site. We reviewed two groups
      of consecutive patients undergoing operations for vascular access at different
      centers. Group 1 had a SAVF protocol in place during the study period with
      specific criteria for timing SAVF construction. Patients from group 2 were
      referred for evaluation by nephrologists or dialysis nurses as access problems
      were recognized, without a formal protocol in place. All patients had
      preoperative ultrasound or contrast imaging in addition to physical examination.
      Indications for creating a SAVF were AVG thrombosis, dysfunction, erosion,
      bleeding, or steal syndrome involving the existing AVG. The simple presence of a
      functional AVG without evidence of dysfunction was not an indication for
      conversion to a SAVF. SAVFs were classified according to location and the
      potential for utilizing the existing mature AVG outflow vein. Group 1: 40
      consecutive patients, age 26-78 (mean = 62), 42% were female; 55% were diabetic.
      These patients had 1-22 previous access operations (mean = 3). 92.5% underwent
      SAVF surgery prior to loss of the AVG, minimizing catheter use. Cumulative
      patency was 92.5% at 1 year and 87.5% at 2 years. Group 2: 102 consecutive
      patients, age 24-87 (mean = 55), 52% were female; 50% were diabetic. These
      patients had 1-50 previous access operations (mean = 3). Only 19.3% were referred
      for SAVF surgery prior to loss of the AVG or outflow vein. Cumulative patency was
      94.4% at 1 year and 91.6% at 2 years. Failure, dysfunction, or complications of
      AVGs may be resolved by conversion to a SAVF. Further, the limited lifespan of
      AVGs and the superiority of AVFs dictates that a plan be in place to transition
      the AVG patient to an AVF. Most, if not all, hemodialysis patients whose access
      is an AVG will have one or more anatomic sites and vessels suitable for an
      autogenous SAVF. Vessel mapping is critical in the evaluation of failing AVGs and
      in preparation for a SAVF. Cumulative patency rates exceeded 90% at 12 months for
      SAVFs in both patient groups in this report. The need for catheters was
      dramatically less in the patient group with an established SAVF conversion plan.

PMID- 18627563
TI  - Hemodialysis graft with blind loop inflow segment treated with stent placement.
AB  - We report a case of occlusion of a graft related to residual thrombus collection
      at the inflow in a blind pouch formed by conversion of a previous brachial
      cephalic fistula to a graft. The thrombus was unable to be dislodged by
      conventional methods with the use of a Fogarty balloon and maceration of thrombus
      with angioplasty. A covered stent was placed at the inflow segment over this
      thrombus in order to restore the flow through the graft. Angiographic evidence
      for this case is also reported.

PMID- 18627565
TI  - Medical director contracting.
AB  - Those nephrologists who are entering into new, or re-negotiating old, medical
      director contracts should take into consideration the large number of changes in
      the environment that have a bearing on the structure and wording of proposed
      contracts. This contribution offers specific guidance to assist with those
      efforts.

PMID- 18627566
TI  - Cardiac problems in the dialysis patient: beyond coronary disease.
AB  - In end-stage renal disease (ESRD) both an inappropriately high sympathetic drive
      and the activation of tissue-based renin-angiotensin systems lead to a complex
      pattern of comorbidity appearing early on in renal disease. In this context,
      uremic cardiomyopathy, diabetes, and renal failure display an intimate
      interaction that critically defines the prognosis in dialysis patients.
      Importantly, patients with moderate to severe loss of renal function not only
      carry a high burden of traditional cardiovascular risk factors, but also are
      exposed to uremia-specific risk factors that in concert induce an excessively
      increased cardiovascular mortality. Although cardiovascular guidelines may not
      simply be applicable to ESRD patients--these have invariably been excluded from
      larger cardiovascular trials--an early cardiological workup appears rational as
      the prevailing mode of death is characterized by sudden cardiac death and heart
      failure. This short review will therefore go beyond coronary heart disease, focus
      on the specific cardiac pathology in renal failure, and summarize the
      contemporary therapeutic strategies in ESRD.

PMID- 18627567
TI  - Sympathetic overactivity--the Cinderella of cardiovascular risk factors in
      dialysis patients.
AB  - Cardiovascular morbidity and mortality is exceedingly high in patients with
      chronic renal failure. Sympathetic overactivity is an important pathomechanism
      contributing to progression of renal disease as well as cardiovascular
      complications. For more than 30 years it has been known that plasma levels of
      norepinephrine are elevated in chronic renal failure pointing to increased
      sympathetic nerve activity. The kidneys are richly innervated by efferent
      sympathetic and afferent sensory nerves. They participate in many reflex
      adjustments of renal function. Initially, this finding had not been attributed to
      increased efferent sympathetic drive, but rather to reduced renal clearance and
      defective neuronal reuptake of norepinephrine. At this time, however, the
      evidence for increased sympathetic drive is solid. Interventions to reduce
      sympathetic overactivity will provide new therapeutic approaches. The available
      experimental and clinical evidence to suggest such a pathophysiological role of
      sympathetic overactivity is summarized in this current review.

PMID- 18627568
TI  - Sudden cardiac death and dialysis patients.
AB  - Dialysis patients have extraordinarily high mortality rates. The death rate for
      all US dialysis patients in 2004 was 230 per 1000 patient-years. Cardiac disease
      is the major cause of death in dialysis patients and accounts for 43% of all
      cause mortality. In the United States Renal Data System database 62% of cardiac
      deaths (or 27% of all deaths) are attributable to arrhythmic mechanisms. The
      estimated rate of sudden cardiac death in US dialysis patients in 2002 was 7% per
      year. There are several plausible explanations for the special vulnerability of
      dialysis patients to sustaining sudden cardiac death. Obstructive coronary artery
      disease, coupled with diminished tolerance to myocardial ischemia (in the setting
      of myocardial fibrosis and left ventricular hypertrophy), rapid electrolyte
      shifts in hemodialysis patients, and derangements in autonomic function may all
      contribute to this heightened risk of sudden cardiac death. This review focuses
      on the epidemiology of sudden cardiac death in dialysis patients, underlying
      mechanisms of sudden death, and potential interventions to reduce the risk of
      sudden cardiac death in dialysis patients (including medical therapy and
      defibrillators). It is unlikely that one single therapeutic intervention will
      prevent sudden cardiac death in dialysis patients; but a more modest (and
      attainable) goal is the implementation of multiple strategies to reduce the risk
      of sudden cardiac death in this special high-risk population.

PMID- 18627569
TI  - Hypertrophy and fibrosis in the cardiomyopathy of uremia--beyond coronary heart
      disease.
AB  - Cardiac disease is the leading cause of death in uremic patients. In contrast to
      previous opinion, coronary events account for a relatively small proportion of
      cardiac deaths, the most common causes being sudden death and heart failure.
      Against this background the current text will discuss noncoronary cardiac
      pathology, specifically the pathogenesis and the morphological findings caused by
      (pathological) cardiac hypertrophy, cardiac interstitial fibrosis and
      microvascular disease.

PMID- 18627571
TI  - Memory T cells in cancer immunotherapy: which CD8 T-cell population provides the
      best protection against tumours?
AB  - Cancer immunotherapy strategies often fail because of immunosuppressive
      mechanisms present in the tumour-bearing host. Adoptive T-cell transfer therapy
      circumvents this problem by activating tumour-specific CD8(+) T cells in vitro
      and transferring them back into the patient. Classically, effector T cells have
      been used in these studies because of their potent anti-tumour activity. However,
      it is becoming apparent that highly activated effector cells may become
      terminally differentiated, display impaired proliferation and survival in vivo,
      and mediate short-term anti-tumour effects. In contrast to effector cells, memory
      cells have enhanced proliferative potential and survival, and the potential to
      provide more robust and enduring protection against tumours. Here, we discuss key
      studies in the field of adoptive T-cell transfer, along with some of our own
      results relating to this area. Based on the body of existing research, it is
      clear that CD8(+) T cells with memory potential are superior to terminally
      differentiated effectors in mediating successful tumour clearance. Opinions
      remain divided as to whether the central memory or effector memory T-cell subset
      is capable of providing the best protection against tumours. We propose that as
      these cell types have different but complementary benefits for the anti-tumour
      immune response, the ideal cell population to use for adoptive T-cell transfer
      should consist of a heterogeneous mixture of memory cells.

PMID- 18627570
TI  - Investigation of CD69 as a new candidate gene for rheumatoid arthritis.
AB  - The aim of this study was to investigate the CD69 gene as a new functional
      candidate gene for rheumatoid arthritis (RA) genetic predisposition. A case
      control association study including 933 RA patients and 800 healthy individuals
      was conducted. Five haplotype-tagging single nucleotide polymorphisms (SNPs)
      (rs929615, rs3176806, rs4763299, rs11052877, and rs3176789) covering the CD69
      gene coding, 5' and 3' untranslated regions were selected as CD69 genetic markers
      and genotyped using a Taqman 5' allelic discrimination assay. No statistically
      significant differences were observed in the single marker association study with
      regard to either genotypic or allelic frequencies when considering the rs929615,
      rs3176806, rs4763299, rs11052877, and rs3176789 CD69 SNPs independently.
      According to these findings, no statistically significant skewing was observed
      between the RA patients and the controls in the distribution of CD69 haplotypes.
      In summary, our results do not support a major role for the CD69 gene
      polymorphisms in RA genetic predisposition in our population.

PMID- 18627572
TI  - New insights of HLA class I association to Behcet's disease in Portuguese
      patients.
AB  - Human leukocyte antigen (HLA)-B*51 is a well-known genetic factor associated with
      Behcet's disease (BD). To analyse the influence of HLA-B*51 and other HLA class I
      alleles in BD susceptibility in a Portuguese population and its association with
      disease severity, we studied 78 BD patients and 208 healthy controls. The
      patients were classified into two severity groups as described by Gul et al. As
      expected, a higher frequency of HLA-B*51 was found. The frequency of HLA-Cw*16
      alleles was significantly higher in patients. Regarding severity, HLA-B*27
      frequency was higher in the severe group compared with controls and with the mild
      group. Thus, HLA-B*51 and HLA-Cw*16 seem to confer susceptibility to BD in this
      patients. HLA-B*27 may be important as a prognostic factor.

PMID- 18627573
TI  - Chromatin tethering of incoming foamy virus by the structural Gag protein.
AB  - Retroviruses hijack cellular machineries to productively infect their hosts.
      During the early stages of viral replication, proviral integration relies on
      specific interactions between components of the preintegration complex and host
      chromatin-bound proteins. Here, analyzing the fate of incoming primate foamy
      virus, we identify a short domain within the C-terminus of the structural Gag
      protein that efficiently binds host chromosomes, by interacting with H2A/H2B core
      histones. While viral particle production, virus entry and intracellular
      trafficking are not affected by mutation of this domain, chromosomal attachment
      of incoming subviral complexes is abolished, precluding proviral integration. We
      thus highlight a new function of the structural foamy Gag protein as the main
      tether between incoming subviral complexes and host chromatin prior to
      integration.

PMID- 18627574
TI  - Intermediate organelles of the plant secretory pathway: identity and function.
AB  - The secretory pathway of eukaryotic cells comprises a network of organelles that
      connects three large membranes, the plasma membrane, the vacuole and the
      endoplasmic reticulum. The Golgi apparatus and the various post-Golgi organelles
      that control vacuolar sorting, secretion and endocytosis can be regarded as
      intermediate organelles of the endocytic and biosynthetic routes. Many processes
      in the secretory pathway have evolved differently in plants and cannot be studied
      using yeast or mammalian cells as models. The best characterized organelles are
      the Golgi apparatus and the prevacuolar compartment, but recent work has shed
      light on the role of the trans Golgi network, which has to be regarded as a
      separate organelle in plants. In this study, we wish to highlight recent findings
      regarding the late secretory pathway and its crosstalk with the early secretory
      pathway as well as the endocytic route in plants. Recently published findings and
      suggested models are discussed within the context of known features of the
      equivalent pathway in other eukaryotes.

PMID- 18627575
TI  - Identification of acidic dileucine signals in LRP9 that interact with both GGAs
      and AP-1/AP-2.
AB  - The Golgi-localized, gamma-ear-containing, ADP ribosylation factor-binding family
      of monomeric clathrin adaptors (GGAs) is known to bind cargo molecules through
      short C-terminal peptide motifs conforming to the sequence DXXLL (X = any amino
      acid), while the heterotetrameric adaptors AP-1 and AP-2 utilize a similar but
      discrete sorting motif of the sequence [D,E]XXXL[L,I]. While it has been
      established that a single cargo molecule may contain either or both types of
      these acidic cluster-dileucine (AC-LL) sorting signals, there are no examples of
      cargo with overlapping GGA and AP-1/AP-2-binding motifs. In this study, we report
      that the cytosolic tail of low-density lipoprotein receptor-related protein
      (LRP)9 contains a bifunctional GGA and AP-1/AP-2-binding motif at its carboxy
      terminus (EDEPLL). We further demonstrate that the internal EDEVLL sequence of
      LRP9 also binds to GGAs in addition to AP-2. Either AC-LL motif of LRP9 is
      functional in endocytosis. These findings represent the first study
      characterizing the trafficking of LRP9 and also have implications for the
      identification of additional GGA cargo molecules.

PMID- 18627576
TI  - The luminal domain of p23 (Tmp21) plays a critical role in p23 cell surface
      trafficking.
AB  - p23 (Tmp21 or p24delta), a member of the p24 family, is important for maintaining
      the integrity of the secretory pathway in mammals. It is a type I protein with a
      receptor-like luminal domain and a short cytoplasmic tail. This cytoplasmic tail
      carries an atypical endoplasmic reticulum (ER) retention KKXX motif that binds to
      coat protein I. The trafficking of p23 has been thought to be restricted to the
      early secretory pathway. However, recent findings as well as this study
      demonstrate that p23 is also found in the plasma membrane. By tagging different
      domains of p23 with green fluorescent protein, it is shown that it is the luminal
      domain that is primarily responsible for the appearance of p23 in the plasma
      membrane, despite the presence of a functional KKXX-ER retention and retrieval
      motif. When the KKXX motif is abolished, p23 shows an extremely increased
      trafficking to the plasma membrane. These experiments reveal the presence of two
      fractions of p23 with distinct trafficking destinations. One fraction cycles
      through the ER-Golgi pathway using its functional KKXX retrieval motif. The
      transient appearance of p23 in the plasma membrane is supported by the luminal
      domain. These results help to explain the functional presence of p23 in plasma
      membrane protein complexes and post-Golgi compartments.

PMID- 18627577
TI  - Endosomal functions in plants.
AB  - Plant endosomes are highly dynamic organelles that are involved in the
      constitutive recycling of plasma membrane cargo and the trafficking of polarized
      plasma membrane proteins such as auxin carriers. In addition, recent studies have
      shown that surface receptors such as the plant defense-related FLS2 receptor and
      the brassinosteroid receptor BRI1 appear to signal from endosomes upon ligand
      binding and internalization. In yeast and mammals, endosomes are also known to
      recycle vacuolar cargo receptors back to the trans Golgi network and sort
      membrane proteins for degradation in the vacuole/lysosome. Some of these sorting
      mechanisms are mediated by the retromer and endosomal sorting complex required
      for transport (ESCRT) complexes. Plants contain orthologs of all major retromer
      and ESCRT complex subunits, but they have also evolved variations in endosomal
      functions connected to plant-specific features such as the diversity of vacuolar
      transport pathways. This review focuses on recent studies in plants dealing with
      the regulation of endosomal recycling functions, architecture and formation of
      multivesicular bodies, ligand-mediated endocytosis and receptor signaling from
      endosomes as well as novel endosomal markers and the function of endosomes in the
      transport and processing of soluble vacuolar proteins.

PMID- 18627578
TI  - Use of the cytomegalovirus pp65 antigenemia assay for preemptive therapy in
      allogeneic hematopoietic stem cell transplantation: a real-world review.
AB  - Despite advances in surveillance strategies and antivirals, cytomegalovirus (CMV)
      infection continues to pose problems to patients receiving hematopoietic stem
      cell transplants (HSCTs). The bone marrow transplant (BMT) unit at the Singapore
      General Hospital embraced the preemptive strategy in late 2003. Although several
      studies have demonstrated its usefulness, we conducted this review to document
      CMV-related events at our institution. Forty-six patients underwent CMV
      surveillance using the CMV pp65 antigenemia (CMV Ag) assay from January 2004 to
      December 2005. Twenty-seven patients had CMV infection, and 19 remained
      antigenemia-negative. No differences were found between the 2 groups for the
      following potential risk factors for CMV infection: age, total number of co
      morbidities, duration of neutropenia after conditioning, baseline creatinine,
      type of conditioning regimen (conventional vs. reduced intensity), type of
      transplant (matched sibling vs. others), recipient CMV status, donor CMV status,
      and use of total body irradiation. Two patients received alemtuzumab; both
      developed CMV Ag. Twelve episodes of CMV infection occurred after the 100th post
      HSCT day. Two patients developed CMV disease. One of them could be considered a
      failure of the preemptive strategy, as she had CMV gastritis diagnosed on the
      same day that she became pp65-positive. The other developed CMV disease despite
      prompt institution of ganciclovir, although she had multiple post-HSCT
      complications requiring enhanced immunosuppression, as well as relapsed disease.
      One-year disease-free survival was 55.5% in those with CMV infection and 52.3% in
      those without infection. Survival was not affected by CMV infection.

PMID- 18627579
TI  - Primary cutaneous mucormycosis in a lung transplant recipient: case report and
      concise review of the literature.
AB  - Mucormycosis (zygomycosis) is an invasive, opportunistic fungal infection caused
      by organisms of the class Zygomycetes. Immunocompromised individuals, including
      both solid organ and hematopoietic stem cell transplant recipients, are
      preferentially affected. Among solid organ transplant (SOT) recipients, the
      sinuses, with or without involvement of the orbits and cerebrum, are the most
      common sites of disease, although the pulmonary allograft appears to be targeted
      following lung transplantation. Here, we describe the unique case of a lung
      transplant recipient who developed multifocal cutaneous mucormycosis without
      involvement of the pulmonary allograft, and review the published literature
      regarding incidence, treatment, and prognosis of primary cutaneous mucormycosis
      following SOT.

PMID- 18627580
TI  - Real-time PCR on the first galactomannan-positive serum sample for diagnosing
      invasive aspergillosis in liver transplant recipients.
AB  - Invasive aspergillosis (IA) is a life-threatening complication of liver
      transplantation. Detection of circulating galactomannan (GM) in serum samples is
      a method to improve the microbiological diagnosis in patients at risk for IA.
      However, the assay is hampered by false-positive results. The search for
      circulating Aspergillus DNA in the first GM-positive sample could improve the
      specificity of the test. Among 484 liver transplant recipients followed in a
      single center over 4 years, 25 patients had at least 1 GM-positive serum sample.
      The threshold of GM positivity was a ratio >or=1. These 25 patients were
      classified by the clinicians as probable IA (n=11), possible IA (n=2), and no IA
      (n=12) using the EORTC/MSG criteria with blinding to the polymerase chain
      reaction (PCR) results. After 1 mL aliquots of the first GM-positive serum sample
      were thawed, 2 independent DNA extractions were performed using the MagNA Pure
      Compact apparatus. Real-time amplification targeted at Aspergillus fumigatus
      mitochondrial DNA was performed on 10 microL of the final eluate in duplicate in
      the 2 independent DNA extractions using a LightCycler instrument. A sample was
      considered positive when the crossing point was <or=43 cycles in at least 2 out
      of the 4 replicates. Among the 13 probable or possible IA, 8 patients were PCR
      positive. The other 12 patients who had no IA were all PCR negative. Our data
      suggest that a concomitant real-time PCR performed on the first GM-positive
      sample improves the specificity of the first GM-positive assay result.

PMID- 18627581
TI  - Hookworm, Ascaris lumbricoides infection and polyparasitism associated with poor
      cognitive performance in Brazilian schoolchildren.
AB  - OBJECTIVE: To investigate the relationship between hookworm and Ascaris
      lumbricoides infection and performance on three subsets of the Wechsler
      Intelligence Scale for Children - third edition (WISC-III) (Digit Span,
      Arithmetic and Coding) and Raven Colored Progressive Matrices. METHODS: Cross
      sectional study of 210 children between the ages of 6 and 11 years in
      Americaninhas, Minas Gerais, Brazil. Separate proportional odds models were used
      to measure the association between the intensity of helminth infections and poor
      performance on each of the four cognitive tests. RESULTS: After adjusting for
      sex, age, socioeconomic status and other helminth infections, moderate-to-high
      intensity hookworm infection was associated with poor performance on the WISC-III
      Coding subtest [OR = 3.20; 95% confidence interval (CI) = 1.43-7.17], low
      intensity of hookworm infection was associated with poor performance on the WISC
      III Coding subtest [odds ratio (OR) = 3.71; 95% CI = 1.80-7.66] and moderate-to
      high-intensity A. lumbricoides infection was associated with poor performance on
      the Raven test (OR = 2.03; 95% CI = 1.04-3.99), all in comparison with uninfected
      children. Children co-infected with A. lumbricoides infection and hookworm
      infection had greater odds of poor performance on some WISC-III subtests than
      children with only A. lumbricoides infection. CONCLUSIONS: These findings suggest
      that hookworm infection may be associated with poorer concentration and
      information processing skills, as measured on the WISC-III Coding subtest, and
      that A. lumbricoides infection may be associated with poorer general
      intelligence, as measured through the Raven Colored Progressive Matrices. This
      study also presents evidence that polyparasitized children experience worse
      cognitive outcomes than children with only one helminth infection.

PMID- 18627582
TI  - It is nice to have options.

PMID- 18627583
TI  - The need for uniform definitions in the regionalized care of ST-segment elevation
      myocardial infarction.

PMID- 18627585
TI  - Inappropriate use of antibiotics for acute asthma in United States emergency
      departments.
AB  - OBJECTIVES: The aim was to examine the use of antibiotics to treat asthma
      patients in U.S. emergency departments (EDs). The authors sought to investigate
      inappropriate antibiotic prescriptions by identifying the frequency and
      predictors of antibiotics prescribed for asthma exacerbations using data from two
      sources, the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the
      National Emergency Department Safety Study (NEDSS). METHODS: The authors used
      data from NHAMCS and NEDSS to identify the proportion of ED visits for asthma
      exacerbations that resulted in the prescription of an antibiotic. NHAMCS provided
      national data from 1993 through 2004, while NEDSS provided data from 63 primarily
      academic EDs from 2003 through 2006. Univariate analysis and multivariate
      logistic regression modeling were used to identify variables associated with
      antibiotic administration. RESULTS: Analysis of NHAMCS data revealed that 22%
      (95% confidence interval [CI] = 20% to 24%) of acute asthma visits resulted in an
      antibiotic prescription from 1993 through 2004, with no significant change in
      prescribing frequency over the 12-year period. NEDSS data from 2003 through 2006
      showed that 18% (95% CI = 17% to 19%) of acute asthma cases in academic EDs
      received an antibiotic. Multivariate modeling of NHAMCS data revealed that
      African American patients (odds ratio [OR] = 0.8; 95% CI = 0.6 to 0.97) and
      patients in urban EDs (OR = 0.5; 95% CI = 0.4 to 0.7) were less likely to receive
      antibiotics for asthma exacerbations than white patients and patients in nonurban
      EDs, respectively. NHAMCS analysis also found that patients in the South were
      more likely to receive antibiotics than those in the Northeast (OR = 1.4; 95% CI
      = 1.1 to 1.9). A NEDSS multivariate model found a similar difference, with
      African Americans (OR = 0.6; 95% CI = 0.4 to 0.8) and Hispanics (OR = 0.6; 95% CI
      = 0.4 to 0.8) being less likely than whites to receive an antibiotic.
      CONCLUSIONS: ED treatment of acute asthma with unnecessary antibiotics is likely
      to contribute to bacterial antibiotic resistance. Interventions are needed to
      reduce inappropriate antibiotic prescriptions and to address disparities in
      asthma care.

PMID- 18627587
TI  - Medical malpractice: utilization of layered simulation for resident education.
AB  - OBJECTIVES: The authors present a novel approach to the use of simulation in
      medical education with a two-event layered simulation. A patient care simulation
      with an adverse outcome was followed by a simulated deposition. METHODS: Senior
      residents in an academic emergency medicine (EM) program were solicited as
      simulation research volunteers. Other than stating that the research involved
      adverse outcomes, no identifying information was given. Seven volunteers
      participated in a simulation involving a forced error (nurse confederate gave an
      incorrect medication dose). Six weeks later based on the initial simulation, one
      physician completed a simulated deposition in a teaching conference conducted by
      a licensed attorney with malpractice experience. The audience, consisting of
      residents, attendings, and students, watched a recording of the patient care,
      witnessed the deposition, and evaluated the experience using a 17-question survey
      with 5-point Likert scales. RESULTS: Participants felt that overall the training
      program was a useful educational tool (mean +/- standard deviation [SD] Likert
      score = 4.63 +/- 0.49) that would change aspects of their practice (3.31 +/-
      0.85). Participants stated that they would be more careful in their documentation
      (3.88 +/- 0.60), review high-risk situations with staff (4.00 +/- 0.71), and
      monitor more carefully for errors (3.95 +/- 0.74). There was increased fear of
      the litigation process (3.95 +/- 1.18), but participants felt the experience
      would help improve the risk profile of their practices (3.71 +/- 0.68).
      CONCLUSIONS: A novel approach to medical education was successful in changing
      attitudes and provided an expanded educational experience for participants.
      Layered simulation can be successfully incorporated into educational programs for
      numerous issues including medical malpractice.

PMID- 18627591
TI  - Reliability and validity of the Romanian version of a scale to measure infant
      feeding attitudes and knowledge.
AB  - AIM: To describe the development and testing of the Romanian version of the Iowa
      Infant Feeding Attitude Scale (IIFAS-R). The original instrument has well
      established psychometrics for use in English-speaking countries. METHODS:
      Questionnaires including demographics and items about prior pregnancy and
      opinions about breastfeeding in public were administered to women in Cluj-Napoca,
      Romania, attending antenatal clinic (n = 336) and to a separate cohort of mothers
      within 24 h of delivery (n = 276). Postpartum follow-up was conducted with a
      sample of maternity cohort subjects who initiated breastfeeding in the hospital
      (n = 52). RESULTS: Internal consistency was adequate in both cohorts (antenatal
      alpha= 0.50; maternity alpha= 0.63), with improved reliability for antenatal
      multigravid (alpha= 0.60) and university-educated women (alpha= 0.57). Score
      distributions were comparable and item means were approximately central across
      cohorts. Among pregnant women, higher scores (more positive towards
      breastfeeding) were associated with longer planned maternity leave (chi2= 17.8; p
      = 0.02). Higher maternity cohort scores were associated with age (r = 0.31, p =
      0.003), urban residence (chi2= 10.2, p = 0.04), breastfeeding a prior infant for
      at least 6 weeks (chi2= 6.4, p = 0.04), and with intending to breastfeed for at
      least 6 weeks (chi2= 4.7, p = 0.03). Postpartum women still breastfeeding at
      follow-up also scored higher (chi2= 9.3, p = 0.009). CONCLUSION: This is the
      first study to report on use of the IIFAS in Eastern Europe. The IIFAS-R is easy
      to administer, reliable and valid in Romania. The IIFAS-R can support data
      collection to promote and assess breastfeeding initiatives consistent with World
      Health Organization recommendations.

PMID- 18627592
TI  - The complete mitochondrial genome of the bag-shelter moth Ochrogaster lunifer
      (Lepidoptera, Notodontidae).
AB  - BACKGROUND: Knowledge of animal mitochondrial genomes is very important to
      understand their molecular evolution as well as for phylogenetic and population
      genetic studies. The Lepidoptera encompasses more than 160,000 described species
      and is one of the largest insect orders. To date only nine lepidopteran
      mitochondrial DNAs have been fully and two others partly sequenced. Furthermore
      the taxon sampling is very scant. Thus advance of lepidopteran mitogenomics
      deeply requires new genomes derived from a broad taxon sampling. In present work
      we describe the mitochondrial genome of the moth Ochrogaster lunifer. RESULTS:
      The mitochondrial genome of O. lunifer is a circular molecule 15593 bp long. It
      includes the entire set of 37 genes usually present in animal mitochondrial
      genomes. It contains also 7 intergenic spacers. The gene order of the newly
      sequenced genome is that typical for Lepidoptera and differs from the insect
      ancestral type for the placement of trnM. The 77.84% A+T content of its alpha
      strand is the lowest among known lepidopteran genomes. The mitochondrial genome
      of O. lunifer exhibits one of the most marked C-skew among available insect
      Pterygota genomes. The protein-coding genes have typical mitochondrial start
      codons except for cox1 that present an unusual CGA. The O. lunifer genome
      exhibits the less biased synonymous codon usage among lepidopterans. Comparative
      genomics analysis study identified atp6, cox1, cox2 as cox3, cob, nad1, nad2,
      nad4, and nad5 as potential markers for population genetics/phylogenetics
      studies. A peculiar feature of O. lunifer mitochondrial genome it that the
      intergenic spacers are mostly made by repetitive sequences. CONCLUSION: The
      mitochondrial genome of O. lunifer is the first representative of superfamily
      Noctuoidea that account for about 40% of all described Lepidoptera. New genome
      shares many features with other known lepidopteran genomes. It differs however
      for its low A+T content and marked C-skew. Compared to other lepidopteran genomes
      it is less biased in synonymous codon usage. Comparative evolutionary analysis of
      lepidopteran mitochondrial genomes allowed the identification of previously
      neglected coding genes as potential phylogenetic markers. Presence of repetitive
      elements in intergenic spacers of O. lunifer genome supports the role of DNA
      slippage as possible mechanism to produce spacers during replication.

PMID- 18627593
TI  - Chlamydial genes shed light on the evolution of photoautotrophic eukaryotes.
AB  - BACKGROUND: Chlamydiae are obligate intracellular bacteria of protists,
      invertebrates and vertebrates, but have not been found to date in photosynthetic
      eukaryotes (algae and embryophytes). Genes of putative chlamydial origin,
      however, are present in significant numbers in sequenced genomes of
      photosynthetic eukaryotes. It has been suggested that such genes were acquired by
      an ancient horizontal gene transfer from Chlamydiae to the ancestor of
      photosynthetic eukaryotes. To further test this hypothesis, an extensive search
      for proteins of chlamydial origin was performed using several recently sequenced
      algal genomes and EST databases, and the proteins subjected to phylogenetic
      analyses. RESULTS: A total of 39 proteins of chlamydial origin were retrieved
      from the photosynthetic eukaryotes analyzed and their identity verified through
      phylogenetic analyses. The distribution of the chlamydial proteins among four
      groups of photosynthetic eukaryotes (Viridiplantae, Rhodoplantae, Glaucoplantae,
      Bacillariophyta) was complex suggesting multiple acquisitions and losses.
      Evidence is presented that all except one of the chlamydial genes originated from
      an ancient endosymbiosis of a chlamydial bacterium into the ancestor of the
      Plantae before their divergence into Viridiplantae, Rhodoplantae and
      Glaucoplantae, i.e. more than 1.1 BYA. The chlamydial proteins subsequently
      spread through secondary plastid endosymbioses to other eukaryotes. Of 20
      chlamydial proteins recovered from the genomes of two Bacillariophyta, 10 were of
      rhodoplant, and 10 of viridiplant origin suggesting that they were acquired by
      two different secondary endosymbioses. Phylogenetic analyses of concatenated
      sequences demonstrated that the viridiplant secondary endosymbiosis likely
      occurred before the divergence of Chlorophyta and Streptophyta. CONCLUSION: We
      identified 39 proteins of chlamydial origin in photosynthetic eukaryotes
      signaling an ancient invasion of the ancestor of the Plantae by a chlamydial
      bacterium accompanied by horizontal gene transfer. Subsequently, chlamydial
      proteins spread through secondary endosymbioses to other eukaryotes. We conclude
      that intracellular chlamydiae likely persisted throughout the early history of
      the Plantae donating genes to their hosts that replaced their
      cyanobacterial/plastid homologs thus shaping early algal/plant evolution before
      they eventually vanished.

PMID- 18627594
TI  - Modelling lifetime cost consequences of ReSTOR in cataract surgery in four
      European countries.
AB  - BACKGROUND: To compare the lifetime costs of liberating patients from spectacles
      after cataract surgery by implanting the multifocal intraocular lens (IOL)
      'ReSTOR' versus monofocal IOLs in France, Italy, Germany and Spain. METHODS: A
      Markov model was created to follow patient cohorts from cataract surgery until
      death. Prevalence rates of patients not needing spectacles after cataract surgery
      were obtained from clinical trials. Resource utilisation included implant
      surgery, IOLs, spectacles, visits to ophthalmologists and eye centres, transport,
      and time lost by patients. Economic perspectives were those of Society and
      Sickness Funds (SFs). RESULTS: The mean number of spectacles purchased after
      ReSTOR was 1.34-1.61 and after monofocal IOLs 6.05-7.27. From the societal
      perspective, total cost estimates discounted by 3% were between 3,551 euros and
      4,052 euros with ReSTOR compared to 3,989 euros and 5,548 euros with monofocal
      IOLs. Undiscounted savings related to ReSTOR ranged from 815 euros to 2,164
      euros. From the SFs' perspective total cost estimates discounted by 3% were
      between 2,150 euros and 2,524 euros with ReSTOR compared to 2,324 euros and 2,610
      euros with monofocal IOLs. Savings related to ReSTOR, once costs discounted,
      ranged from 61 euros to 219 euros. Discount and spectacle freedom prevalence
      rates were the most sensitive parameters. CONCLUSION: The bulk of the savings
      related to ReSTOR were realized outside the SF. From both a societal and SF
      perspective, savings, after a 3% discounting, achieved by liberating patients
      from spectacles counterbalanced the initially higher cost of ReSTOR. ReSTOR is a
      cost saving alternative to spectacles for patients requiring cataract surgery.

PMID- 18627595
TI  - A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation
      to secondary sex ratio.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous industrial chemicals
      that persist in the environment and in human fatty tissue. PCBs are related to a
      class of compounds known as dioxins, specifically 2,3,7,8-TCDD (tetrachloro
      dibenzodioxin), which has been implicated as a cause of altered sex ratio,
      especially in relation to paternal exposures. METHODS: In the 1960's, serum
      specimens were collected from pregnant women participating in the Child Health
      and Development Study in the San Francisco Bay Area. The women were interviewed
      and their serum samples stored at -20 degrees C. For this study, samples were
      thawed and a total of eleven PCBs were determined in 399 specimens. Secondary sex
      ratio, or sex ratio at birth, was evaluated as a function of maternal serum
      concentrations using log-binomial and logistic regression, controlling for
      hormonally active medications taken during pregnancy. RESULTS: The relative risk
      of a male birth decreased by 33% comparing women at the 90th percentile of total
      PCBs with women at the 10th percentile (RR = 0.67; 95% CI, 0.48-0.94; p = 0.02),
      or by approximately 7% for each 1 mug/L increase in total PCB concentration.
      Although some congener-specific associations with sex ratio were only marginally
      statistically significant, all nine PCB congeners with < 30% of samples below the
      LOQ showed the same direction of association, an improbable finding under the
      null hypothesis. CONCLUSION: Maternal exposure to PCBs may be detrimental to the
      success of male sperm or to the survival of male embryos. Findings could be due
      to contaminants, metabolites or PCBs themselves.

PMID- 18627596
TI  - The function of BCL9 in Wnt/beta-catenin signaling and colorectal cancer cells.
AB  - BACKGROUND: Most cases of colorectal cancer are initiated by hyperactivation of
      the Wnt/beta-catenin pathway due to mutations in the APC tumour suppressor, or in
      beta-catenin itself. A recently discovered component of this pathway is Legless,
      which is essential for Wnt-induced transcription during Drosophila development.
      Limited functional information is available for its two mammalian relatives, BCL9
      and B9L/BCL9-2: like Legless, these proteins bind to beta-catenin, and RNAi
      mediated depletion of B9L/BCL9-2 has revealed that this protein is required for
      efficient beta-catenin-mediated transcription in mammalian cell lines. No loss-of
      function data are available for BCL9. METHODS: We have used overexpression of
      dominant-negative forms of BCL9, and RNAi-mediated depletion, to study its
      function in human cell lines with elevated Wnt pathway activity, including
      colorectal cancer cells. RESULTS: We found that BCL9 is required for efficient
      beta-catenin-mediated transcription in Wnt-stimulated HEK 293 cells, and in the
      SW480 colorectal cancer cell line whose Wnt pathway is active due to APC
      mutation. Dominant-negative mutants of BCL9 indicated that its function depends
      not only on its beta-catenin ligand, but also on an unknown ligand of its C
      terminus. Finally, we show that BCL9 and B9L are both Wnt-inducible genes,
      hyperexpressed in colorectal cancer cell lines, indicating that they are part of
      a positive feedback loop. CONCLUSION: BCL9 is required for efficient beta-catenin
      mediated transcription in human cell lines whose Wnt pathway is active, including
      colorectal cancer cells, indicating its potential as a drug target in colorectal
      cancer.

PMID- 18627597
TI  - Presence of Helicobacter pylori in a Mexican Pre-Columbian Mummy.
AB  - BACKGROUND: Recent studies showed that Helicobacter pylori existed in the New
      World prior to the arrival of Columbus. The purpose of the present study was to
      detect the presence of Helicobacter pylori in pre-Columbian mummies from Northern
      Mexico. METHODS: Six samples were studied (four samples of gastric remains,
      tongue-soft palate, and brain remained as negative controls) from two of the six
      naturally mummified corpses studied (adult male and infant male). Samples were
      taken from tissues suitable for DNA amplification by Polymerase chain reaction
      (PCR). DNA was extracted and H. pylori detection was carried out by PCR and
      hybridized with the pHp probe from 16S rRNA gene. The purified PCR products were
      cloned and sequenced in both directions. DNA sequences were analyzed with ALIGN
      and BLAST software. A second amplification was performed using ureB gene by real
      time PCR. RESULTS: From four samples of gastric remnant, only two were H. pylori
      positive for amplification of a 109 bp DNA fragment; the remaining two were
      negative, as were the tongue-soft palate and the brain biopsies as well. These
      PCR products were hybridized with a pHp probe. Nucleotide sequence analysis
      showed homology with H. pylori in 98 of 99% when compared with the gene bank
      nucleotide sequence. Only one sample of gastric remnant H. pylori-positive with
      16S rRNA gene was also positive for ureB gene from H. pylori. CONCLUSION: This
      data supported infection with H. pylori in Mexican pre-Columbian mummies dating
      from approximately 1,350 AC.

PMID- 18627598
TI  - Low nucleosome occupancy is encoded around functional human transcription factor
      binding sites.
AB  - BACKGROUND: Transcriptional regulation of genes in eukaryotes is achieved by the
      interactions of multiple transcription factors with arrays of transcription
      factor binding sites (TFBSs) on DNA and with each other. Identification of these
      TFBSs is an essential step in our understanding of gene regulatory networks, but
      computational prediction of TFBSs with either consensus or commonly used
      stochastic models such as Position-Specific Scoring Matrices (PSSMs) results in
      an unacceptably high number of hits consisting of a few true functional binding
      sites and numerous false non-functional binding sites. This is due to the
      inability of the models to incorporate higher order properties of sequences
      including sequences surrounding TFBSs and influencing the positioning of
      nucleosomes and/or the interactions that might occur between transcription
      factors. RESULTS: Significant improvement can be expected through the development
      of a new framework for the modeling and prediction of TFBSs that considers
      explicitly these higher order sequence properties. It would be particularly
      interesting to include in the new modeling framework the information present in
      the nucleosome positioning sequences (NPSs) surrounding TFBSs, as it can be
      hypothesized that genomes use this information to encode the formation of stable
      nucleosomes over non-functional sites, while functional sites have a more open
      chromatin configuration. In this report we evaluate the usefulness of the latter
      feature by comparing the nucleosome occupancy probabilities around experimentally
      verified human TFBSs with the nucleosome occupancy probabilities around false
      positive TFBSs and in random sequences. CONCLUSION: We present evidence that
      nucleosome occupancy is remarkably lower around true functional human TFBSs as
      compared to non-functional human TFBSs, which supports the use of this feature to
      improve current TFBS prediction approaches in higher eukaryotes.

PMID- 18627599
TI  - MalHaploFreq: a computer programme for estimating malaria haplotype frequencies
      from blood samples.
AB  - BACKGROUND: Molecular markers, particularly those associated with drug
      resistance, are important surveillance tools that can inform policy choice.
      People infected with falciparum malaria often contain several genetically
      distinct clones of the parasite; genotyping the patients' blood reveals whether
      or not the marker is present (i.e. its prevalence), but does not reveal its
      frequency. For example a person with four malaria clones may contain both mutant
      and wildtype forms of a marker but it is not possible to distinguish the relative
      frequencies of the mutant and wildtypes i.e. 1:3, 2:2 or 3:1. METHODS: An
      appropriate method for obtaining frequencies from prevalence data is by Maximum
      Likelihood analysis. A computer programme has been developed that allows the
      frequency of markers, and haplotypes defined by up to three codons, to be
      estimated from blood phenotype data. RESULTS: The programme has been fully
      documented [see Additional File 1] and provided with a user-friendly interface
      suitable for large scale analyses. It returns accurate frequencies and 95%
      confidence intervals from simulated dataset sets and has been extensively tested
      on field data sets. CONCLUSION: The programme is included [see Additional File 2]
      and/or may be freely downloaded from 1. It can then be used to extract molecular
      marker and haplotype frequencies from their prevalence in human blood samples.
      This should enhance the use of frequency data to inform antimalarial drug policy
      choice.

PMID- 18627600
TI  - Structure and properties of transcriptional networks driving selenite stress
      response in yeasts.
AB  - BACKGROUND: Stress responses provide valuable models for deciphering the
      transcriptional networks controlling the adaptation of the cell to its
      environment. We analyzed the transcriptome response of yeast to toxic
      concentrations of selenite. We used gene network mapping tools to identify
      functional pathways and transcription factors involved in this response. We then
      used chromatin immunoprecipitation and knock-out experiments to investigate the
      role of some of these regulators and the regulatory connections between them.
      RESULTS: Selenite rapidly activates a battery of transcriptional circuits,
      including iron deprivation, oxidative stress and protein degradation responses.
      The mRNA levels of several transcriptional regulators are themselves regulated.
      We demonstrate the existence of a positive transcriptional loop connecting the
      regulator of proteasome expression, Rpn4p, to the pleiotropic drug response
      factor, Pdr1p. We also provide evidence for the involvement of this regulatory
      module in the oxidative stress response controlled by the Yap1p transcription
      factor and its conservation in the pathogenic yeast C. glabrata. In addition, we
      show that the drug resistance regulator gene YRR1 and the iron homeostasis
      regulator gene AFT2 are both directly regulated by Yap1p. CONCLUSION: This work
      depicted a highly interconnected and complex transcriptional network involved in
      the adaptation of yeast genome expression to the presence of selenite in its
      chemical environment. It revealed the transcriptional regulation of PDR1 by
      Rpn4p, proposed a new role for the pleiotropic drug resistance network in stress
      response and demonstrated a direct regulatory connection between oxidative stress
      response and iron homeostasis.

PMID- 18627601
TI  - Antimicrobial activity of two South African honeys produced from indigenous
      Leucospermum cordifolium and Erica species on selected micro-organisms.
AB  - BACKGROUND: Honey has been shown to have wound healing properties which can be
      ascribed to its antimicrobial activity. The antimicrobial activity can be
      effective against a broad spectrum of bacterial species especially those of
      medical importance. It has also been shown that there is considerable variation
      in the antimicrobial potency of different types of honey, which is impossible to
      predict. With this in mind we tested the antimicrobial activity of honeys
      produced from plants grown in South Africa for their antibacterial properties on
      selected standard strains of oral micro-organisms. METHODS: The honeys used were
      produced from the blossoms of Eucalyptus cladocalyx (Bluegum) trees, an
      indigenous South African plant Leucospermum cordifolium (Pincushion), a mixture
      of wild heather shrubs, mainly Erica species (Fynbos) and a Leptospermum
      scoparium (Manuka) honey. Only pure honey which had not been heated was used. The
      honeys were tested for their antimicrobial properties with a broth dilution
      method. RESULTS: Although the honeys produced some inhibitory effect on the
      growth of the micro-organisms, no exceptionally high activity occurred in the
      South African honeys. The carbohydrate concentration plays a key role in the
      antimicrobial activity of the honeys above 25%. However, these honeys do contain
      other antimicrobial properties that are effective against certain bacterial
      species at concentrations well below the hypertonic sugar concentration. The
      yeast C. albicans was more resistant to the honeys than the bacteria. The species
      S. anginosus and S. oralis were more sensitive to the honeys than the other test
      bacteria. CONCLUSION: The honeys produced from indigenous wild flowers from South
      Africa had no exceptionally high activity that could afford medical grade status.

PMID- 18627602
TI  - A meta-analysis of the efficacy of fibromyalgia treatment according to level of
      care.
AB  - INTRODUCTION: The aim of this paper was to compare the efficacy of the treatments
      for fibromyalgia currently available in both primary care and specialised
      settings. METHODS: Published reports of randomised controlled trials (RCTs)
      researching pharmacological and non-pharmacological treatments in patients with
      fibromyalgia were found in the MEDLINE, EMBASE, the Cochrane Central Register of
      Controlled Trials and PsychInfo databases. The most recent electronic search was
      undertaken in June 2006. RESULTS: We identified a total of 594 articles. Based on
      titles and abstracts, 102 full articles were retrieved, 33 of which met the
      inclusion criteria. These RCTs assessed 120 treatment interventions in 7789
      patients diagnosed with primary fibromyalgia. Of them, 4505 (57.8%) were included
      in the primary care group of our study and 3284 (42.2%) in the specialised
      intervention group. The sample was mostly made up of middle-aged women, who have
      had fibromyalgia for a mean period of 6 to 10 years. The mean effect size of the
      efficacy of the 120 treatment interventions in patients with fibromyalgia
      compared with controls was 0.49 (95% confidence interval [CI] = 0.39 to 0.58; p <
      0.001). In the primary care group it was 0.46 (95% CI = 0.33 to 0.58) while in
      specialised care it was 0.53 (95% CI = 0.38 to 0.69), with no statistical
      significance in the differences. We analysed the efficacy of treatments by
      comparing primary and specialised care in the different fibromyalgia groups and
      there were no significant differences. The variables of the studies that affected
      the improvements in the efficacy of fibromyalgia treatment were low quality of
      the studies and a shorter duration of treatment. However, both factors were
      biased by the heterogeneity of the studies. Other variables that also improved
      outcome and were not biased by the heterogeneity of the studies, were younger age
      of the patients and shorter duration of the disorder. On the contrary, gender and
      type of treatment (pharmacological vs. psychological) did not affect outcome.
      CONCLUSION: Based on this meta-analysis and despite the heterogeneity of
      specialised care studies and of the other limitations described in this article,
      treating fibromyalgia in specialised care offers no clear advantages.

PMID- 18627603
TI  - Nuptial gifts fail to resolve a sexual conflict in an insect.
AB  - BACKGROUND: Because of the potential benefits to individuals of saving investment
      for future mating opportunities, there is conflict between mates over most
      aspects of reproduction. Males of many species transfer compounds in the
      ejaculate that manipulate female reproductive physiology to increase male
      reproductive success. These seminal compounds are often associated with direct
      and/or indirect costs to females. In contrast, in some species ejaculates also
      contain nutrients used by females for somatic maintenance and increased
      reproductive output. In general, the extent to which male seminal components are
      detrimental or beneficial to females is poorly understood, and interactions
      between seminal compounds with different effects have been almost completely
      neglected. Here we examine the impact of male receptivity-suppressing factors and
      nutrient donations on female longevity and lifetime reproductive output in the
      bushcricket Requena verticalis. RESULTS: We show that receiving multiple
      ejaculates reduces longevity in female R. verticalis, indicating a cost of male
      derived receptivity-suppressing compounds. Consumption of male nutrient donations
      does not appear to ameliorate this longevity cost, and there was no effect of
      nutrient provisioning on female lifetime fecundity. CONCLUSION: These results
      indicate that nutrient provisioning does not provide a resolution to sexual
      conflict over female receptivity in this bushcricket species.

PMID- 18627604
TI  - Variation in DNA methylation patterns of grapevine somaclones (Vitis vinifera
      L.).
AB  - BACKGROUND: In traditional vine areas, the production should present a typicity
      that partly depends on the grapevine variety. Therefore, vine improvement is
      considered difficult because of the limited choice in the natural variability of
      the cultivars within the limits of their characteristics. A possibility to
      circumvent this problem is the use of somatic variability. In vitro somatic
      embryogenesis and organogenesis can lead to genotypic and phenotypic variations,
      described as somaclonal variation, that could be useful for the selection of
      improved grapevine genotypes. RESULTS: In order to study tissue culture-induced
      variation of grapevine, we have analysed 78 somaclones obtained from somatic
      embryos of two distinct cultivars using molecular marker techniques. SSRs were
      only useful to verify the conservation of the microsatellite genotype between the
      somaclones and the respective mother clones. AFLP polymorphism between mother
      clones and somaclones was 1.3-2.8 times higher to that found between clones.
      However, a majority of the somaclones (45/78) exhibited only few changes. Seven
      and five somaclones of 'Chardonnay 96' and 'Syrah 174', respectively, which
      covered at least all polymorphic loci found in AFLP analysis were used for MSAP
      study. All of the 120 polymorphic fragments were found only in the somaclones.
      The percentage of full methylation at CCGG recognition sites was slightly higher
      in somaclones due to more polymorphic bands generated after cleavage by
      EcoRI/HpaII. Different digestion patterns revealed different methylation status,
      especially different levels of de-methylation, that are the consequence of the in
      vitro culture. CONCLUSION: MSAP highlights DNA methylation variation in
      somaclones compared to mother clones and, therefore, is a powerful tool for
      genotypic characterisation of somatic embryo-derived grapevines. The detection of
      the same polymorphic bands in numerous somaclones of different cultivars suggests
      the possibility of hot spots of DNA methylation variation. SSR profiles of the
      'Chardonnay' and 'Syrah' somaclones were the same as of the respective mother
      clones. The somaclones exhibited a higher AFLP variation than clones obtained via
      traditional clonal selection in the field. Therefore, somatic embryogenesis
      through in vitro culture technique could be useful for the selection of improved
      cultivars with subtle changes but conserving their main characteristics.

PMID- 18627605
TI  - Prevalence of widespread pain and associations with work status: a population
      study.
AB  - BACKGROUND: This population study based on a representative sample from a Swedish
      county investigates the prevalence, duration, and determinants of widespread pain
      (WSP) in the population using two constructs and estimates how WSP affects work
      status. In addition, this study investigates the prevalence of widespread pain
      and its relationship to pain intensity, gender, age, income, work status,
      citizenship, civil status, urban residence, and health care seeking. METHODS: A
      cross-sectional survey using a postal questionnaire was sent to a representative
      sample (n = 9952) of the target population (284,073 people, 18-74 years) in a
      county (Ostergotland) in the southern Sweden. The questionnaire was mailed and
      followed by two postal reminders when necessary. RESULTS: The participation rate
      was 76.7% (n = 7637); the non-participants were on the average younger, earned
      less money, and male. Women had higher prevalences of pain in 10 different
      predetermined anatomical regions. WSP was generally chronic (90-94%) and
      depending on definition of WSP the prevalence varied between 4.8-7.4% in the
      population. Women had significantly higher prevalence of WSP than men and the age
      effect appeared to be stronger in women than in men. WSP was a significant
      negative factor - together with age 50-64 years, low annual income, and non
      Nordic citizen - for work status in the community and in the group with chronic
      pain. Chronic pain but not the spreading of pain was related to health care
      seeking in the population. CONCLUSION: This study confirms earlier studies that
      report high prevalences of widespread pain in the population and especially among
      females and with increasing age. Widespread pain is associated with prominent
      effects on work status.

PMID- 18627606
TI  - Gastroesophageal reflux-associated chronic cough in an adolescent and the
      diagnostic implications: a case report.
AB  - A 15-year-old girl was referred with a 2-year history of perennial non-productive
      cough, which had been preceded by Mycoplasma pneumoniae pneumonia and subsequent
      asthma. Symptoms were only partially responsive to anti-asthma treatment
      including an inhaled corticosteroid and a leukotriene receptor antagonist. The
      patient's BMI was 27.8; she had gained over 10 kg in the previous two years.
      Typical symptoms of gastroesophageal reflux disease were not evident except for
      belch. Coughing worsened on eating and rising from bed. Although esophagography
      failed to disclose reflux esophagitis, esophageal pH monitoring revealed
      significant acid reflux. Asthma was considered well controlled. Treatment with
      the proton-pump inhibitor rabeprazole resulted in disappearance of cough.
      Frequency Scale for the Symptoms of Gastroesophageal reflux disease (FSSG) score,
      a questionnaire evaluating the symptoms of gastroesophageal reflux disease, was
      initially high but normalized after treatment. Capsaicin cough sensitivity also
      diminished with treatment.Chronic cough due to gastroesophageal reflux disease
      has been considered rare in adolescents, but this condition might be increasing
      in line with the recent trend in adults. Clinical features of gastroesophageal
      reflux disease-associated cough typical for adult patients and a specific
      questionnaire for evaluating gastroesophageal reflux disease validated in adults
      may also be useful diagnostic clues in adolescents.

PMID- 18627607
TI  - Drug-prescribing patterns during pregnancy in the tertiary care hospitals of
      Pakistan: a cross sectional study.
AB  - BACKGROUND: The rationale for use of drugs during pregnancy requires a careful
      assessment as in addition to the mother, the health and life of her unborn child
      is also at stake. Information on the use of drugs during pregnancy is not
      available in Pakistan. The aim of this study was to evaluate the patterns of drug
      prescriptions to pregnant women in tertiary care hospitals of Pakistan. METHODS:
      This was a cross-sectional study conducted at five tertiary care hospitals of
      Pakistan. Copies of outpatient medicinal prescriptions given to pregnant patients
      attending the antenatal clinics were collected. The drugs were classified
      according to the pharmacological class and their teratogenic potential. RESULTS:
      All the pregnant women attending the antenatal clinics received a prescription
      containing at least one drug. A total of 3769 distinct prescriptions given to
      different women were collected. Majority of the women who received the
      prescriptions belonged to third trimester (55.4%) followed by second (33.6%) and
      first trimester (11.0%). On an average, each prescription contained 1.66 +/- 0.14
      drugs. The obstetricians at Civil Hospital, Karachi and Chandka Medical College
      Hospital, Larkana showed a tendency of prescribing lesser number of drugs
      compared to those in other hospitals. Anti-anemic drugs including iron
      preparations and vitamin and mineral supplements (79.4%) were the most frequently
      prescribed drugs followed by analgesics (6.2%) and anti-bacterials (2.2%). 739
      women (19.6%) received prescriptions containing drugs other than vitamin or
      mineral supplements. Only 1275 (21.6%) of all the prescribed drugs (n = 6100)
      were outside this vitamin/mineral supplement class. Out of these 1275 drugs, 29
      (2.3%) drugs were prescribed which are considered to be teratogenic. Misoprostol
      was the most frequently prescribed (n = 6) among the teratogenic drugs followed
      by carbimazole (n = 5) and methotrexate (n = 5). Twenty nine pregnant women (0.8%
      of all the women studied) were prescribed these teratogenic drugs. CONCLUSION:
      Less than one percent of the pregnant women attending tertiary care hospitals in
      Pakistan are prescribed teratogenic drugs. The prescribing practices of Pakistani
      physicians are similar to those in western countries.

PMID- 18627608
TI  - The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) is a potential
      prognostic marker in human breast cancer.
AB  - INTRODUCTION: ISG15 is an ubiquitin-like molecule that is strongly upregulated by
      type I interferons as a primary response to diverse microbial and cellular stress
      stimuli. However, alterations in the ISG15 signalling pathway have also been
      found in several human tumour entities. To the best of our knowledge, in the
      current study we present for the first time a systematic characterisation of
      ISG15 expression in human breast cancer and normal breast tissue both at the mRNA
      and protein level. METHOD: Using semiquantitative real-time PCR, cDNA dot-blot
      hybridisation and immunohistochemistry, we systematically analysed ISG15
      expression in invasive breast carcinomas (n = 910) and normal breast tissues (n =
      135). ISG15 protein expression was analysed in two independent cohorts on tissue
      microarrays; in an initial evaluation set of 179 breast carcinomas and 51 normal
      breast tissues; and in a second large validation set of 646 breast carcinomas and
      10 normal breast tissues. In addition, a collection of benign and malignant
      mammary cell lines (n = 9) were investigated for ISG15 expression. RESULTS: ISG15
      was overexpressed in breast carcinoma cells compared with normal breast tissue,
      both at the RNA and protein level. Recurrence-free (p = 0.030), event-free (p =
      0.001) and overall (p = 0.001) survival analyses showed a significant correlation
      between ISG15 overexpression and unfavourable prognosis. CONCLUSION: Therefore,
      ISG15 may represent a novel breast tumour marker with prognostic significance and
      may be helpful in selecting patients for and predicting response to the treatment
      of human breast cancer.

PMID- 18627609
TI  - Different outcome of six homozygotes for prothrombin A20210A gene variant.
AB  - Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous
      thrombotic disease while conflicting results have been reported for the risk of
      arterial thrombotic events. However, vascular episodes were absent in up to 40%
      of the 67 homozygotes for the G20210A described so far, which indicates that the
      clinical expression depends on additional risk/trigger factors. We describe six
      homozygotes for the G20210A variant, among which the first pair of siblings
      (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous
      clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of
      common femoral, superficial and popliteal veins. She assumed oral contraceptives
      in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy
      loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced
      arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old)
      and stroke (48 years old), respectively, in absence of other risk factors.
      Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant
      being consanguineous of symptomatic subjects bearing the variant, did not
      experience any episode of venous nor arterial disease. Both of them have chronic
      liver disease with an impairement of the prothrombin time INR. Thus, homozygotes
      for the G20210A are at risk for arterial (in addition to venous) thromobotic
      events; chronic liver disease might modulate this risk.

PMID- 18627610
TI  - ATP-induced autophagy is associated with rapid killing of intracellular
      mycobacteria within human monocytes/macrophages.
AB  - BACKGROUND: We have previously reported that ATP treatment of M bovis-BCG
      infected human macrophages induces P2X7 receptor-dependent killing of
      intracellular mycobacteria. The mechanism mediating this bactericidal effect has
      not been full characterized but is known to be Ca2+-dependent and to promote the
      maturation and acidification of mycobacteria-containing phagosomes. In this study
      we demonstrate that the ATP/P2X7-mediated, mycobactericidal effect also involves
      the induction of cell autophagy. RESULTS: We report that 3 mM ATP induces rapid
      cell autophagy in THP1 cells and monocyte-derived macrophages within 30 minutes
      post-treatment, as revealed by the expression of LC3-II bands on western blot
      analysis. Using Ca2+-free media and selective P2X7 agonists and antagonists, ATP
      induced cell autophagy was shown to be Ca2+ and P2X7 receptor-dependent. Electron
      microscopy of ATP-treated, BCG-infected MDMs revealed the presence of the
      bacteria within characteristic double-membraned autophagosomes. Confocal analysis
      further confirmed that pharmacological inhibition of autophagy by wortmannin or
      pre-treatment of macrophages with anti-P2X7 antibody blocked ATP-induced phago
      lysosomal fusion. Induction of cell autophagy with ATP was also temporally
      associated with a fall in intracellular mycobacterial viability, which was
      suppressed by treatment with wortmannin or the selective P2X7 antagonist,
      oxidized ATP (oATP). CONCLUSION: We provide the first evidence that ATP/P2X7
      mediated killing of intracellular mycobacteria involves the induction of cell
      autophagy. The findings support the hypothesis that autophagy plays a key role in
      the control of mycobacterial infections.

PMID- 18627611
TI  - Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis
      as an ancient function of the p53 family.
AB  - BACKGROUND: In contrast to the three mammalian p53 family members, p53, which is
      generally involved in DNA damage responses, and p63 and p73 which are primarily
      needed for developmental regulation, cep-1 encodes for the single C. elegans p53
      like gene. cep-1 acts as a transcription activator in a primordial p53 pathway
      that involves CEP-1 activation and the CEP-1 dependent transcriptional induction
      of the worm BH3 only domain encoding genes egl-1 and ced-13 to induce germ cell
      apoptosis. EGL-1 and CED-13 proteins inactivate Bcl-2 like CED-9 to trigger CED-4
      and CED-3 caspase dependent germ cell apoptosis. To address the function of p53
      in global transcriptional regulation we investigate genome-wide transcriptional
      responses upon DNA damage and cep-1 deficiency. RESULTS: Examining C. elegans
      expression profiles using whole genome Affymetrix GeneChip arrays, we found that
      83 genes were induced more than two fold upon ionizing radiation (IR). None of
      these genes, with exception of an ATP ribosylase homolog, encode for known DNA
      repair genes. Using two independent cep-1 loss of function alleles we did not
      find genes regulated by cep-1 in the absence of IR. Among the IR-induced genes
      only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans
      specific gene. The majority of IR-induced genes appear to be involved in general
      stress responses, and qRT-PCR experiments indicate that they are mainly expressed
      in somatic tissues. Interestingly, we reveal an extensive overlap of gene
      expression changes occurring in response to DNA damage and in response to
      bacterial infection. Furthermore, many genes induced by IR are also
      transcriptionally regulated in longevity mutants suggesting that DNA damage and
      aging induce an overlapping stress response. CONCLUSION: We performed genome-wide
      gene expression analyses which indicate that only a surprisingly small number of
      genes are regulated by CEP-1 and that DNA damage induced apoptosis via the
      transcriptional induction of BH3 domain proteins is likely to be an ancient DNA
      damage response function of the p53 family. Interestingly, although the apoptotic
      response to DNA damage is regulated through the transcriptional activity of CEP
      1, other DNA damage responses do not appear to be regulated on the
      transcriptional level and do not require the p53 like gene cep-1.

PMID- 18627612
TI  - Cigarette smoke worsens lung inflammation and impairs resolution of influenza
      infection in mice.
AB  - BACKGROUND: Cigarette smoke has both pro-inflammatory and immunosuppressive
      effects. Both active and passive cigarette smoke exposure are linked to an
      increased incidence and severity of respiratory virus infections, but underlying
      mechanisms are not well defined. We hypothesized, based on prior gene expression
      profiling studies, that upregulation of pro-inflammatory mediators by short term
      smoke exposure would be protective against a subsequent influenza infection.
      METHODS: BALB/c mice were subjected to whole body smoke exposure with 9
      cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71
      strain), and analyzed 3 and 10 days later (d3, d10). These time points are the
      peak and resolution (respectively) of influenza infection. RESULTS: Inflammatory
      cell influx into the bronchoalveolar lavage (BALF), inflammatory mediators,
      proteases, histopathology, viral titres and T lymphocyte profiles were analyzed.
      Compared to smoke or influenza alone, mice exposed to smoke and then influenza
      had more macrophages, neutrophils and total lymphocytes in BALF at d3, more
      macrophages in BALF at d10, lower net gelatinase activity and increased activity
      of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key
      cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus
      specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before
      influenza infection had close to 10-fold higher lung virus titres at d3 than
      influenza alone mice, although all mice had cleared virus by d10, regardless of
      smoke exposure. Smoke exposure caused temporary weight loss and when smoking
      ceased after viral infection, smoke and influenza mice regained significantly
      less weight than smoke alone mice. CONCLUSION: Smoke induced inflammation does
      not protect against influenza infection.In most respects, smoke exposure worsened
      the host response to influenza. This animal model may be useful in studying how
      smoke worsens respiratory viral infections.

PMID- 18627613
TI  - Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell
      activation.
AB  - BACKGROUND: Leukotriene B4 (LTB4) is a potent inflammatory mediator that also
      stimulates the immune response. In addition, it promotes polymorphonuclear
      leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release.
      Regarding chemical instability of the leukotriene molecule, in the present study
      we assessed the immunomodulatory activities conferred by LTB4 released from
      microspheres (MS). A previous oil-in-water emulsion solvent extraction
      evaporation method was chosen to prepare LTB4-loaded MS. RESULTS: In the mice
      cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS
      provoked significant increases in leukocyte rolling flux, adhesion and emigration
      besides significant decreases in the leukocyte rolling velocity. LTB4-loaded MS
      also increase peroxisome proliferator-activated receptor-alpha (PPARalpha)
      expression by murine peritoneal macrophages and stimulate them to generate
      nitrite levels. Monocyte chemoattractant protein-1 (MCP-1) and nitric oxide (NO)
      productions were also increased when human umbilical vein and artery endothelial
      cells (HUVECs and HUAECs, respectively) were stimulated with LTB4-loaded MS.
      CONCLUSION: LTB4-loaded MS preserve the biological activity of the encapsulated
      mediator indicating their use as a new strategy to modulate cell activation,
      especially in the innate immune response.

PMID- 18627614
TI  - Practice characteristics and prescribing of cardiovascular drugs in areas with
      higher risk of CHD in Scotland: cross-sectional study.
AB  - BACKGROUND: We examine whether practices in areas with higher risks of CHD
      prescribe different levels of cardiovascular drugs and describe how they differ
      in GP and practice characteristics. METHODS: Propensity score matching was used
      to identify two groups of practices in Scotland. The cases were in areas with 5%
      or more of the population in South Asian ethnic groups. The controls were in
      areas with less than 1% of the population in South Asian ethnic groups and were
      matched for other population characteristics. RESULTS: The 39 case practices have
      lower prescribing rates than the matched controls for all heart disease drugs
      Significant different are found for six drugs (statins, ace Inhibitors,
      clopidogrel, thiazides, warfarin and digoxin. The differences range from 12.8%
      less for amlodipine to 43.9% for clopidogrel. The case practices also have lower
      prescribing costs than the unmatched group with the exception of ace inhibitors
      and aspirin. The highest prescribing costs for all drugs are found in the matched
      control group. The case practices are smaller than the controls, and have fewer
      GPs per 1,000 patients. Case practices have fewer quality markers and receive
      less in total resources, but have higher sums reimbursed to cover their employed
      staff costs. CONCLUSION: Patients with higher risk of CHD tend to live in areas
      served by practices with lower prescribing rates and poorer structural
      characteristics. The scale of the differences in prescribing suggests that health
      care system factors rather than individual treatment decisions cause inequity in
      care. Identifying whether South Asian individuals are less likely to receive
      heart disease drugs than non South Asians requires individual-level prescribing
      data, which is currently not available in the UK.

PMID- 18627615
TI  - Spontaneous splenic rupture mimicking pneumonia: a case report.
AB  - A 74-year-old gentleman presented with a history of left-sided pleuritic chest
      and upper abdominal pain. Examination and chest x-ray findings were suggestive of
      pneumonia. An abdominal ultrasound was suggestive of spontaneous splenic rupture.
      An abdominal computed tomography scan showed a splenic laceration and large peri
      splenic haematoma. The advice from the on-call surgical team was to treat
      conservatively but the patient's condition deteriorated suddenly and he died.
      Spontaneous splenic rupture is uncommon but probably under-diagnosed and should
      be considered in all patients presenting with non-specific abdominal pain. The
      optimal management strategy for the older patient with spontaneous ruptured
      spleen is unknown.

PMID- 18627616
TI  - Use of multiple methods for genotyping Fusarium during an outbreak of contact
      lens associated fungal keratitis in Singapore.
AB  - BACKGROUND: In Singapore, an outbreak of fungal keratitis caused by members of
      the Fusarium solani species complex (FSSC) was identified in March 2005 to May
      2006 involving 66 patients. Epidemiological investigations have indicated that
      improper contact lens wear and the use of specific contact lens solutions were
      risk factors. METHODS: We assessed the genetic diversity of the isolates using
      AFLP, Rep-PCR, and ERIC-PCR and compared the usefulness of these typing schemes
      to characterize the isolates. RESULTS: AFLP was the most discriminative typing
      scheme and appears to group FSSC from eye infections and from other infections
      differently. CONCLUSION: There was a high genomic heterogeneity among the
      isolates confirming that this was not a point source outbreak.

PMID- 18627617
TI  - Analysis of health related quality of life (HRQoL) of patients with clinically
      localized prostate cancer, one year after treatment with external beam
      radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT).
AB  - PURPOSE: Prostate cancer is the leading form of cancer diagnosed among North
      American men. Most patients present with localized disease, which can be
      effectively treated with a variety of different modalities. These are associated
      with widely different acute and late effects, which can be both physical and
      psychological in nature. HRQoL concerns are therefore important for these
      patients for selecting between the different treatment options. MATERIALS AND
      METHODS: One year after receiving radiotherapy for localised prostate cancer 117
      patients with localized prostate cancer were invited to participate in a quality
      of life (QoL) self reported survey. 111 patients consented and participated in
      the survey, one year after completion of their treatment. 88 patients received
      EBRT and 23 received EBRT and HDRBT. QoL was compared in the two groups by using
      a modified version of Functional Assessment of Cancer Therapy-Prostate (FACT-P)
      survey instrument. RESULTS: One year after completion of treatment, there was no
      significant difference in overall QoL scores between the two groups of patients.
      For each component of the modified FACT-P survey, i.e. physical, social/family,
      emotional, and functional well-being; there were no statistically significant
      differences in the mean scores between the two groups. CONCLUSION: In prostate
      cancer patients treated with EBRT alone versus combined EBRT and HDRBT, there was
      no significant difference in the QoL scores at one year post-treatment.

PMID- 18627618
TI  - Large gene overlaps in prokaryotic genomes: result of functional constraints or
      mispredictions?
AB  - BACKGROUND: Across the fully sequenced microbial genomes there are thousands of
      examples of overlapping genes. Many of these are only a few nucleotides long and
      are thought to function by permitting the coordinated regulation of gene
      expression. However, there should also be selective pressure against long
      overlaps, as the existence of overlapping reading frames increases the risk of
      deleterious mutations. Here we examine the longest overlaps and assess whether
      they are the product of special functional constraints or of erroneous
      annotation. RESULTS: We analysed the genes that overlap by 60 bps or more among
      338 fully-sequenced prokaryotic genomes. The likely functional significance of an
      overlap was determined by comparing each of the genes to its respective
      orthologs. If a gene showed a significantly different length from its orthologs
      it was considered unlikely to be functional and therefore the result of an error
      either in sequencing or gene prediction. Focusing on 715 co-directional overlaps
      longer than 60 bps, we classified the erroneous ones into five categories: i) 5'
      end extension of the downstream gene due to either a mispredicted start codon or
      a frameshift at 5'-end of the gene (409 overlaps), ii) fragmentation of a gene
      caused by a frameshift (163), iii) 3'-end extension of the upstream gene due to
      either a frameshift at 3'-end of a gene or point mutation at the stop codon (68),
      iv) Redundant gene predictions (4), v) 5' & 3'-end extension which is a
      combination of i) and iii) (71). We also studied 75 divergent overlaps that could
      be classified as misannotations of group i). Nevertheless we found some
      convergent long overlaps (54) that might be true overlaps, although an important
      part of convergent overlaps could be classified as group iii) (124). CONCLUSION:
      Among the 968 overlaps larger than 60 bps which we analysed, we did not find a
      single real one among the co-directional and divergent orientations and concluded
      that there had been an excessive number of misannotations. Only convergent
      orientation seems to permit some long overlaps, although convergent overlaps are
      also hampered by misannotations. We propose a simple rule to flag these erroneous
      gene length predictions to facilitate automatic annotation.

PMID- 18627620
TI  - Misleading menorrhagia in a peri-menopausal woman with underlying bowel cancer: a
      case report.
AB  - A peri-menopausal woman presented with symptoms and signs suggestive of
      fibroids. She was fit and healthy with no significant past medical history. She
      consented to having a hysterectomy but her surgery was performed prior to any
      diagnostic imaging being done.At surgery there was an unexpected finding of
      disseminated carcinoma, diffusely infiltrating the uterus, fallopian tubes and
      ovaries. There was an omental cake that was biopsied. Frozen section showed
      signet ring cells, suggesting bowel carcinoma. Further intra-operative
      examination revealed a caecal tumour. After surgery she was investigated further
      and eventually referred for palliation, due to her advanced disease.

PMID- 18627619
TI  - Thermodynamics of binding of divalent magnesium and manganese to uridine
      phosphates: implications for diabetes-related hypomagnesaemia and carbohydrate
      biocatalysis.
AB  - BACKGROUND: Although the necessity of divalent magnesium and manganese for full
      activity of sugar nucleotidyltransferases and glycosyltransferases is well known,
      the role of these metal cations in binding the substrates (uridine 5'
      triphosphate, glucose-1-phosphate, N-acetylglucosamine-1-phosphate, and uridine
      5'-diphosphate glucose), products (uridine 5'-diphosphate glucose, uridine 5'
      diphosphate N-acetylglucosamine, pyrophosphate, and uridine 5'-diphosphate),
      and/or enzyme is not clearly understood. RESULTS: Using isothermal titration
      calorimetry we have studied the binding relationship between the divalent metals,
      magnesium and manganese, and uridine 5'-phosphates to determine the role these
      metals play in carbohydrate biosynthesis. It was determined from the isothermal
      titration calorimetry (ITC) data that Mg(+2) and Mn(+2) are most tightly bound to
      PP(i), K(b) = 41,000 +/- 2000 M(-1) and 28,000 +/- 50,000 M(-1) respectively, and
      UTP, K(b) = 14,300 +/- 700 M(-1) and 13,000 +/- 2,000 M(-1) respectively.
      CONCLUSION: Our results indicate that the formal charge state of the phosphate
      containing substrates determine the binding strength. Divalent metal cations
      magnesium and manganese showed similar trends in binding to the sugar substrates.
      Enthalpy of binding values were all determined to be endothermic except for the
      PP(i) case. In addition, entropy of binding values were all found to be positive.
      From this data, we discuss the role of magnesium and manganese in both sugar
      nucleotidyltransferase and glycosyltransferase reactions, the differences in
      metal-bound substrates expected under normal physiological metal concentrations
      and those of hypomagnesaemia, and the implications for drug design.

PMID- 18627621
TI  - Multiple myeloma presenting with high-output heart failure and improving with
      anti-angiogenesis therapy: two case reports and a review of the literature.
AB  - INTRODUCTION: Common manifestations of multiple myeloma include osteolytic
      lesions, cytopenias, hypercalcemia, and renal insufficiency. Patients may also
      exhibit heart failure which is often associated with either past therapy or
      cardiac amyloidosis. A less recognized mechanism is high-output heart failure.
      Diuretic therapy in this setting has little efficacy in treating the congested
      state. Furthermore, effective pharmacotherapy has not been established. We report
      two patients with multiple myeloma and high-output heart failure who failed
      diuretic therapy. The patients were given dexamethasone in conjunction with
      lenalidomide and thalidomide, respectively. Shortly thereafter, each patient
      demonstrated a significant improvement in symptoms. This is the first report of
      successful treatment of multiple myeloma-induced high-output failure via the
      utilization of these agents. CASE PRESENTATION: Two patients with multiple
      myeloma were evaluated for volume overload. The first was a 50-year-old man with
      refractory disease. Magnetic resonance imaging demonstrated diffuse marrow
      replacement throughout the pelvis. Cardiac catheterization conveyed elevated
      filling pressures and a cardiac output of 15 liters/minute. He quickly
      decompensated and required mechanical ventilation. The second patient was a 61
      year-old man recently diagnosed with multiple myeloma and volume overload.
      Skeletal survey demonstrated numerous lytic lesions throughout the pelvis. His
      cardiac catheterization also conveyed elevated filling pressures and a cardiac
      output of 10 liters/minute. Neither patient responded to diuretic therapy and
      they were subsequently started on dexamethasone plus lenalidomide and
      thalidomide, respectively. The first patient's brisk diuresis allowed for
      extubation within 48 hours after the first dose. He had a net negative fluid
      balance of 15 liters over 10 days. The second patient also quickly diuresed and
      on repeat cardiac catheterization, his cardiac output had normalized to 4.7
      liters/minute. CONCLUSION: Multiple myeloma can cause high-output failure. The
      mechanism is likely extensive bony involvement causing innumerable intramedullary
      arteriovenous fistulas. Diuretic therapy is not effective in treating this
      condition. Lenalidomide and thalidomide, both of which inhibit angiogenesis, seem
      to be viable treatment options. Based on the rapid and effective results seen in
      these two patients, a potential novel mechanism of 'pharmacologic fistula
      ligation' with these agents may be the most effective way to treat this
      presentation.

PMID- 18627622
TI  - Spontaneous intratumoral bleeding and rupture of giant gastric stromal tumor (>
      30 cm) in a young patient.
AB  - BACKGROUND: Few cases of GIST bigger than 15 cm have been reported in medical
      literature, all primarily in elderly patients. We report an unusual case, in
      which a giant gastric GIST - in a young patient - presented as spontaneous
      intratumoral bleeding followed by intraluminal rupture. CASE PRESENTATION: A 37
      year-old man was admitted with an acute onset of abdominal pain. CT showed a 32 x
      25 cm mass with some cystic lesions and areas of calcification. Twelve hours
      after admission the patient presented with an episode of upper GI bleeding, and a
      significant decrease of tumor size and hemoglobin level. An upper endoscopy
      showed a large bulge in the posterior aspect of the gastric wall, and a small
      ulcer with continuous bleeding coming from a central orifice. A subtotal
      gastrectomy was carried out. Pathological examination showed a giant gastric GIST
      measuring 32 x 25 x 21 cm and weighing 3.750 g. Immunohistochemical staining
      demonstrated positive reactivity to C-kit protein, CD34, and alpha-smooth muscle
      actin; but negative reactivity to S-100 protein. CONCLUSION: Intratumoral
      bleeding is a very rare presentation of GIST; preoperative diagnosis is always
      made difficult by the absence of pathognomonic signs or symptoms. Emergency local
      excision with negative margins associated with adjuvant therapy with imatinib
      mesylate remains the main modality of treatment for high risk GISTs.

PMID- 18627623
TI  - Use of computerized dynamic posturography to assess balance in older adults after
      nighttime awakenings using zolpidem as a reference.
AB  - BACKGROUND: Computerized dynamic posturography (CDP) has been used to detect
      balance and stability impairments in adults of all ages. The goal of the current
      pilot study was to evaluate balance in healthy older adults after a middle-of-the
      night awakening and to assess the ability of CDP to measure effects of bedtime
      zolpidem administration. METHODS: Two studies used CDP to evaluate balance in
      healthy older adults (> or = 65 years) during middle-of-the-night awakenings. The
      first study used a drug-free, single-period, within-subject, repeated measures
      study design. Subjects were evaluated during the day, pre-sleep, and 2 hours
      after bedtime for dynamic standing balance using the NeuroCom EquiTest Sensory
      Organization Test (SOT). Pairwise comparisons were made using one-way ANOVA. The
      second study was a single-blind, randomized, placebo-controlled, crossover study
      evaluating the ability of the SOT to measure medication-induced dynamic standing
      balance impairments using the commonly prescribed sleep medication, zolpidem 10
      mg, as a test medication. Assessments were performed at night before zolpidem
      administration and then again 2 hours after bedtime. Comparisons were made
      between the 2 groups using an ANCOVA model. RESULTS: Twelve older adults (mean
      age 68.4 years) were evaluated in the first study. There was no significant
      difference between pre-sleep and middle-of-the-night assessments for the SOT
      composite score (P = 0.439). Eleven older adults (mean age 68.9 years) were
      evaluated in the second study. Zolpidem administration significantly decreased
      the SOT composite score after a middle-of-the-night awakening compared with
      placebo (P < 0.001). CONCLUSION: In healthy older adults, getting up in the
      middle of the night did not have a significant effect on dynamic standing
      balance; however, bedtime administration of zolpidem 10 mg did lead to
      significant impairments. Thus, the SOT was able to measure medication-induced
      dynamic standing balance impairments and may be useful for future studies
      comparing balance effects of medications.

PMID- 18627624
TI  - Lutzomyia adiketis sp. n. (Diptera: Phlebotomidae), a vector of Paleoleishmania
      neotropicum sp. n. (Kinetoplastida: Trypanosomatidae) in Dominican amber.
AB  - BACKGROUND: Amber fossils can be used to trace the history of disease-vector
      associations because microorganisms are preserved "in situ" inside the alimentary
      tract and body cavity of blood-sucking insects. RESULTS: Lutzomyia adiketis sp.
      n. (Phlebotomidae: Diptera) is described from Dominican amber as a vector of
      Paleoleishmania neotropicum sp. n. (Kinetoplastida: Trypanosomatidae). The fossil
      sand fly differs from all previously described extinct and extant members of the
      genus by the following combination of characters: Sc forked with the branches
      meeting the costa and radius veins; wing L/W value of 4.1; a delta value of 18; a
      ratio beta/alpha value of 0.86, and the shape and size of the spatulate rods on
      the ninth sternite. The trypanosomatid is characterized by the structure of its
      promastigotes, amastigotes and paramastigotes and its transmission by an extinct
      species of sand fly. CONCLUSION: Morphological characters show that the fossil
      sand fly is a new extinct species and that it is host to a digenetic species of
      trypanosomatid. This study provides the first fossil evidence that Neotropical
      sand flies were vectors of trypanosomatids in the mid-Tertiary (20-30 mya).

PMID- 18627626
TI  - Pigeon fanciers lung: a case report.
AB  - INTRODUCTION: Pigeon fanciers lung, a form of hypersensitivity pneumonitis, is an
      unusual but important occupational and recreational cause of severe and
      debilitating breathlessness. CASE PRESENTATION: We report the case of a 61-year
      old Caucasian man suffering with severe breathlessness due to pigeon fanciers
      lung. He had previously raced and bred pigeons for 25 years but had discontinued
      the pursuit a decade ago. CONCLUSION: Pigeon fanciers lung can be associated with
      severe debilitating dyspnoea and patients may present many years after exposure
      to avian antigens. Physicians should be encouraged to take a detailed
      occupational and recreational history in any patient presenting with unexplained
      breathlessness.

PMID- 18627625
TI  - Xenohormone transactivities are inversely associated to serum POPs in Inuit.
AB  - BACKGROUND: The persistent organic pollutants (POPs) are highly lipophilic and
      resistant to biodegradation and found in e.g. seafood and marine mammals.
      Greenlandic Inuit have high intake of marine food and thus high POP burden that
      varies according to local conditions and dietary preference. We do for the very
      first time report the serum POP related non-steroidal xenohormone activity of
      Inuit across Greenland. The aims were 1) to determine the integrated xenohormone
      bioactivities as an exposure biomarker of the actual lipophilic serum POP mixture
      measuring the effect on estrogen (ER) and androgen receptor (AR) transactivity in
      citizens from different Greenlandic districts and 2) to evaluate associations to
      serum POP markers (14 PCBs and 10 pesticides) and lifestyle characteristics.
      METHODS: Serum samples from 121 men and 119 women from Nuuk, Sisimiut and Qaanaaq
      were extracted using SPE-HPLC fractionation to obtain the serum POP fraction free
      of endogenous hormones. The serum POP fraction was used for determination of
      xenohormone transactivity using ER and AR reporter gene assays. RESULTS: In
      overall, the xenohormone transactivities differed between districts as well as
      between the genders. Associations between the transactivities and age, n-3/n-6
      and smoker years were observed. The xenoestrogenic and xenoandrogenic
      transactivities correlated negatively to the POPs for the combined female and
      male data, respectively. CONCLUSION: The non-steroidal xenohormone
      transactivities can be used as an integrated biomarker of POP exposure and
      lifestyle characteristics. The actual serum POP mixtures antagonized the age
      adjusted sex hormone receptor functions. Comparison of different study
      populations requires in addition to age inclusion of diet and lifestyle factors.

PMID- 18627627
TI  - A coarsened multinomial regression model for perinatal mother to child
      transmission of HIV.
AB  - BACKGROUND: In trials designed to estimate rates of perinatal mother to child
      transmission of HIV, HIV assays are scheduled at multiple points in time. Still,
      infection status for some infants at some time points may be unknown,
      particularly when interim analyses are conducted. METHODS: Logistic regression
      models are commonly used to estimate covariate-adjusted transmission rates, but
      their methods for handling missing data may be inadequate. Here we propose using
      coarsened multinomial regression models to estimate cumulative and conditional
      rates of HIV transmission. Through simulation, we compare the proposed models to
      standard logistic models in terms of bias, mean squared error, coverage
      probability, and power. We consider a range of treatment effect and visit process
      scenarios, while including imperfect sensitivity of the assay and contamination
      of the endpoint due to early breastfeeding transmission. We illustrate the
      approach through analysis of data from a clinical trial designed to prevent
      perinatal transmission. RESULTS: The proposed cumulative and conditional models
      performed well when compared to their logistic counterparts. Performance of the
      proposed cumulative model was particularly strong under scenarios where treatment
      was assumed to increase the risk of in utero transmission but decrease the risk
      of intrapartum and overall perinatal transmission and under scenarios designed to
      represent interim analyses. Power to estimate intrapartum and perinatal
      transmission was consistently higher for the proposed models. CONCLUSION:
      Coarsened multinomial regression models are preferred to standard logistic models
      for estimation of perinatal mother to child transmission of HIV, particularly
      when assays are missing or occur off-schedule for some infants.

PMID- 18627628
TI  - The relation between Ashworth scores and neuromechanical measurements of
      spasticity following stroke.
AB  - BACKGROUND: Spasticity is a common impairment that follows stroke, and it results
      typically in functional loss. For this reason, accurate quantification of
      spasticity has both diagnostic and therapeutic significance. The most widely used
      clinical assessment of spasticity is the modified Ashworth scale (MAS), an
      ordinal scale, but its validity, reliability and sensitivity have often been
      challenged. The present study addresses this deficit by examining whether
      quantitative measures of neural and muscular components of spasticity are valid,
      and whether they are strongly correlated with the MAS. METHODS: We applied abrupt
      small amplitude joint stretches and Pseudorandom Binary Sequence (PRBS)
      perturbations to both paretic and non-paretic elbow and ankle joints of stroke
      survivors. Using advanced system identification techniques, we quantified the
      dynamic stiffness of these joints, and separated its muscular (intrinsic) and
      reflex components. The correlations between these quantitative measures and the
      MAS were investigated. RESULTS: We showed that our system identification
      technique is valid in characterizing the intrinsic and reflex stiffness and
      predicting the overall net torque. Conversely, our results reveal that there is
      no significant correlation between muscular and reflex torque/stiffness and the
      MAS magnitude. We also demonstrate that the slope and intercept of reflex and
      intrinsic stiffnesses plotted against the joint angle are not correlated with the
      MAS. CONCLUSION: Lack of significant correlation between our quantitative
      measures of stroke effects on spastic joints and the clinical assessment of
      muscle tone, as reflected in the MAS suggests that the MAS does not provide
      reliable information about the origins of the torque change associated with
      spasticity, or about its contributing components.

PMID- 18627629
TI  - Genetic interaction network of the Saccharomyces cerevisiae type 1 phosphatase
      Glc7.
AB  - BACKGROUND: Protein kinases and phosphatases regulate protein phosphorylation, a
      critical means of modulating protein function, stability and localization. The
      identification of functional networks for protein phosphatases has been slow due
      to their redundant nature and the lack of large-scale analyses. We hypothesized
      that a genome-scale analysis of genetic interactions using the Synthetic Genetic
      Array could reveal protein phosphatase functional networks. We apply this
      approach to the conserved type 1 protein phosphatase Glc7, which regulates
      numerous cellular processes in budding yeast. RESULTS: We created a novel glc7
      catalytic mutant (glc7-E101Q). Phenotypic analysis indicates that this novel
      allele exhibits slow growth and defects in glucose metabolism but normal cell
      cycle progression and chromosome segregation. This suggests that glc7-E101Q is a
      hypomorphic glc7 mutant. Synthetic Genetic Array analysis of glc7-E101Q revealed
      a broad network of 245 synthetic sick/lethal interactions reflecting that many
      processes are required when Glc7 function is compromised such as histone
      modification, chromosome segregation and cytokinesis, nutrient sensing and DNA
      damage. In addition, mitochondrial activity and inheritance and lipid metabolism
      were identified as new processes involved in buffering Glc7 function. An
      interaction network among 95 genes genetically interacting with GLC7 was
      constructed by integration of genetic and physical interaction data. The obtained
      network has a modular architecture, and the interconnection among the modules
      reflects the cooperation of the processes buffering Glc7 function. CONCLUSION: We
      found 245 genes required for the normal growth of the glc7-E101Q mutant.
      Functional grouping of these genes and analysis of their physical and genetic
      interaction patterns bring new information on Glc7-regulated processes.

PMID- 18627630
TI  - Competency of Anopheles stephensi mysorensis strain for Plasmodium vivax and the
      role of inhibitory carbohydrates to block its sporogonic cycle.
AB  - BACKGROUND: Despite the abundance of studies conducted on the role of mosquitoes
      in malaria transmission, the biology and interaction of Plasmodium with its
      insect host still holds many mysteries. This paper provides the first study to
      follow the sporogonic cycle of Plasmodium vivax in a wild insecticide-resistant
      mysorensis strain of Anopheles stephensi, a major vector of vivax malaria in
      south-eastern Iran. The study subsequently demonstrates that host-parasite sugar
      binding interactions are critical to the development of this parasite in the
      salivary glands of its mosquito host. The identity of the receptors or sugars
      involved was revealed by a receptor "pre-saturation" strategy in which sugars fed
      to the mosquitoes inhibited normal host-parasite interactions. METHODS: Anopheles
      stephensi mysorensis mosquitoes were artificially infected with P. vivax by
      feeding on the blood of gametocytaemic volunteers reporting to local malaria
      clinics in the Sistan-Baluchistan province of south-eastern Iran. In order to
      determine the inhibitory effect of carbohydrates on sporogonic development,
      vector mosquitoes were allowed to ingest blood meals containing both gametocytes
      and added carbohydrates. The carbohydrates tested were GlcNAc, GalNAc, arabinose,
      fucose, mannose, lactose, glucose and galactose. Sporogonic development was
      assessed by survival of the parasite at both the oocyst and sporozoite stages.
      RESULTS: Oocyst development was observed among nearly 6% of the fed control
      mosquitoes but the overall number of mosquitoes exhibiting sporozoite invasion of
      the salivary glands was 47.5% lower than the number supporting oocysts in their
      midgut. Of the tested carbohydrates, only arabinose and fucose slightly perturbed
      the development of P. vivax oocysts at the basal side of the mosquito midgut, and
      the remaining sugars caused no reductions in oocyst development. Strikingly
      however, sporozoites were completely absent from the salivary glands of
      mosquitoes treated with mannose, GalNAc, and lactose. CONCLUSION: The study
      indicates that An. stephensi in southern Iran has the potential to survive long
      enough to be re-infected and transmit vivax malaria several times, based on the
      average adult female longevity (about 30 days) and its gonotrophic cycle (2-3
      days) during the malaria transmission season. Certain sugar binding interactions
      are important for the development of P. vivax sporozoites, and this information
      may be instrumental for the development of transmission blocking strategies.

PMID- 18627631
TI  - Unexplained chest/epigastric pain in patients with normal endoscopy as a
      predictor for ischemic heart disease and mortality: a Danish 10-year cohort
      study.
AB  - BACKGROUND: Normal upper endoscopy may be a marker of ischemic heart disease in
      patients with unexplained chest/epigastric pain. METHODS: We examined the 10-year
      risk of ischemic heart disease and mortality in a cohort of 386 Danish patients
      with chest/epigastric pain, normal upper endoscopy, and no prior hospital
      discharge diagnosis of ischemic heart disease (defined as patients with
      unexplained chest/epigastric pain), compared with 3,793 population controls
      matched by age, gender, and residence. Outcome data were obtained from population
      based health registries. Cox regression analysis was used to estimate the
      relative risk of hospitalization for ischemic heart disease and the adjusted
      mortality rate ratio (MRR). RESULTS: The 10-year relative risk of hospitalization
      for ischemic heart disease following a normal upper endoscopy among patients with
      unexplained chest/epigastric pain was 1.6 (95% CI, 1.1-2.2), compared with
      controls. The 10-year MRR was 1.1 (95% CI, 0.9-1.5). Within the first year after
      the upper endoscopy the MRR was 2.4 (95% CI, 1.3-4.5). The cause-specific MRR
      among patients with unexplained chest/epigastric pain compared with controls was
      up to threefold higher for deaths related to alcohol dependence, pneumonia, and
      lung cancer. CONCLUSION: Unexplained chest/epigastric pain in patients with
      normal endoscopy is a strong marker for ischemic heart disease and increased
      mortality.

PMID- 18627632
TI  - Reliability and validity of two frequently used self-administered physical
      activity questionnaires in adolescents.
AB  - BACKGROUND: To create and find accurate and reliable instruments for the
      measurement of physical activity has been a challenge in epidemiological studies.
      We investigated the reliability and validity of two different physical activity
      questionnaires in 71 adolescents aged 13-18 years; the WHO, Health Behaviour in
      Schoolchildren (HBSC) questionnaire, and the International Physical Activity
      Questionnaire (IPAQ, short version). METHODS: The questionnaires were
      administered twice (8-12 days apart) to measure reliability. Validity was
      assessed by comparing answers from the questionnaires with a cardiorespiratory
      fitness test (VO2peak) and seven days activity monitoring with the ActiReg, an
      instrument measuring physical activity level (PAL) and total energy expenditure
      (TEE). RESULTS: Intraclass correlation coefficients for reliability for the WHO
      HBSC questionnaire were 0.71 for frequency and 0.73 for duration. For the
      frequency question, there was a significant difference between genders; 0.87 for
      girls and 0.59 for boys (p < 0.05). The intraclass correlation coefficients the
      IPAQ varied between 0.10 and 0.62 for the reliability. Spearman correlation
      coefficients for validity for both the WHO HBSC questionnaire and the IPAQ
      (recoded into low, moderate and high activity) measured against VO2peak were
      fair, ranging between 0.29 - 0.39. The WHO HBSC questionnaire measured against
      VO2peak for girls were acceptable, ranging between 0.30 - 0.55. Both
      questionnaires, except the walking question in IPAQ, showed a low correlation
      with PAL and TEE, ranging between 0.01 and 0.29. CONCLUSION: These data indicate
      that the WHO HBSC questionnaire had substantial reliability and were acceptable
      instrument for measuring cardiorespiratory fitness, especially among girls. None
      of the questionnaires however seemed to be a valid instrument for measuring
      physical activity compared to TEE and PAL in adolescents.

PMID- 18627633
TI  - Molecular phylogeny of diplomonads and enteromonads based on SSU rRNA, alpha
      tubulin and HSP90 genes: implications for the evolutionary history of the double
      karyomastigont of diplomonads.
AB  - BACKGROUND: Fornicata is a relatively recently established group of protists that
      includes the diplokaryotic diplomonads (which have two similar nuclei per cell),
      and the monokaryotic enteromonads, retortamonads and Carpediemonas, with the more
      typical one nucleus per cell. The monophyly of the group was confirmed by
      molecular phylogenetic studies, but neither the internal phylogeny nor its
      position on the eukaryotic tree has been clearly resolved. RESULTS: Here we have
      introduced data for three genes (SSU rRNA, alpha-tubulin and HSP90) with a wide
      taxonomic sampling of Fornicata, including ten isolates of enteromonads,
      representing the genera Trimitus and Enteromonas, and a new undescribed
      enteromonad genus. The diplomonad sequences formed two main clades in individual
      gene and combined gene analyses, with Giardia (and Octomitus) on one side of the
      basal divergence and Spironucleus, Hexamita and Trepomonas on the other. Contrary
      to earlier evolutionary scenarios, none of the studied enteromonads appeared
      basal to diplokaryotic diplomonads. Instead, the enteromonad isolates were all
      robustly situated within the second of the two diplomonad clades. Furthermore,
      our analyses suggested that enteromonads do not constitute a monophyletic group,
      and enteromonad monophyly was statistically rejected in 'approximately unbiased'
      tests of the combined gene data. CONCLUSION: We suggest that all higher taxa
      intended to unite multiple enteromonad genera be abandoned, that Trimitus and
      Enteromonas be considered as part of Hexamitinae, and that the term
      'enteromonads' be used in a strictly utilitarian sense. Our result suggests
      either that the diplokaryotic condition characteristic of diplomonads arose
      several times independently, or that the monokaryotic cell of enteromonads
      originated several times independently by secondary reduction from the
      diplokaryotic state. Both scenarios are evolutionarily complex. More comparative
      data on the similarity of the genomes of the two nuclei of diplomonads will be
      necessary to resolve which evolutionary scenario is more probable.

PMID- 18627634
TI  - Extended Field Laser Confocal Microscopy (EFLCM): combining automated Gigapixel
      image capture with in silico virtual microscopy.
AB  - BACKGROUND: Confocal laser scanning microscopy has revolutionized cell biology.
      However, the technique has major limitations in speed and sensitivity due to the
      fact that a single laser beam scans the sample, allowing only a few microseconds
      signal collection for each pixel. This limitation has been overcome by the
      introduction of parallel beam illumination techniques in combination with cold
      CCD camera based image capture. METHODS: Using the combination of microlens
      enhanced Nipkow spinning disc confocal illumination together with fully automated
      image capture and large scale in silico image processing we have developed a
      system allowing the acquisition, presentation and analysis of maximum resolution
      confocal panorama images of several Gigapixel size. We call the method Extended
      Field Laser Confocal Microscopy (EFLCM). RESULTS: We show using the EFLCM
      technique that it is possible to create a continuous confocal multi-colour mosaic
      from thousands of individually captured images. EFLCM can digitize and analyze
      histological slides, sections of entire rodent organ and full size embryos. It
      can also record hundreds of thousands cultured cells at multiple wavelength in
      single event or time-lapse fashion on fixed slides, in live cell imaging chambers
      or microtiter plates. CONCLUSION: The observer independent image capture of EFLCM
      allows quantitative measurements of fluorescence intensities and morphological
      parameters on a large number of cells. EFLCM therefore bridges the gap between
      the mainly illustrative fluorescence microscopy and purely quantitative flow
      cytometry. EFLCM can also be used as high content analysis (HCA) instrument for
      automated screening processes.

PMID- 18627635
TI  - Pulmonary valve endocarditis caused by right ventricular outflow obstruction in
      association with sinus of valsalva aneurysm: a case report.
AB  - BACKGROUND: Right-sided infective endocarditis is uncommon. This is primarily
      seen in patients with intravenous drug use, pacemaker or central venous lines, or
      congenital heart disease. The vast majority of cases involve the tricuspid valve.
      Isolated pulmonary valve endocarditis is extremely rare. We report the first case
      of a pulmonary valve nonbacterial thrombotic endocarditis caused by right
      ventricular outlflow tract (RVOT) obstruction in association with a large sinus
      of Valsalva aneurysm. CASE PRESENTATION: A 60-year-old man with a six-week
      history of fever, initially treated as pneumonia and sinusitis with levofloxacin,
      was admitted to the hospital with a new onset of a heart murmur. An
      echocardiogram showed thickening of the pulmonary valve suggestive of valve
      vegetation. A dilated aortic root and sinus of Valsalva aneurysm measuring at
      least 6.4 cm were also identified. The patient was empirically treated for
      infective endocarditis with vancomycin and gentamycin for 28 days. Four months
      later, the patient underwent resection of a large aortic root aneurysm and
      exploration of the pulmonary valve. During the surgery, vegetation of the
      pulmonary valve was confirmed. Microscopic pathological examination revealed
      fibrinous debris with acute inflammation and organizing fibrosis with chronic
      inflammation, compatible with a vegetation. Special stains were negative for
      bacteria and fungi. CONCLUSION: This is the first case report of a pulmonary
      valve nonbacterial endocarditis caused by RVOT obstruction in association with a
      sinus of Valsalva aneurysm. We speculate that jets created by the RVOT
      obstruction and large sinus of Valsalva aneurysm hitting against endothelium of
      the pulmonary valve is the etiology of this rare nonbacterial thrombotic
      endocarditis.

PMID- 18627636
TI  - Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical
      Asian country (Malaysia) with a relatively low incidence of breast cancer.
AB  - INTRODUCTION: The cost of genetic testing and the limited knowledge about the
      BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in
      medium- and low-resource countries, including Malaysia. In addition, the
      applicability of many risk-assessment tools, such as the Manchester Scoring
      System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier
      Estimation Algorithm) which were developed based on mutation rates observed
      primarily in Caucasian populations using data from multiplex families, and in
      populations where the rate of breast cancer is higher, has not been widely tested
      in Asia or in Asians living elsewhere. Here, we report the results of genetic
      testing for mutations in the BRCA1 or BRCA2 genes in a series of families with
      breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of
      Malaysia. METHOD: A total of 187 breast cancer patients with either early-onset
      breast cancer (at age </= 40 years) or a personal and/or family history of breast
      or ovarian cancer were comprehensively tested by full sequencing of both BRCA1
      and BRCA2. Two algorithms to predict the presence of mutations, the Manchester
      Scoring System and BOADICEA, were evaluated. RESULTS: Twenty-seven deleterious
      mutations were detected (14 in BRCA1 and 13 in BRCA2), only one of which was
      found in two unrelated individuals (BRCA2 490 delCT). In addition, 47 variants of
      uncertain clinical significance were identified (16 in BRCA1 and 31 in BRCA2).
      Notably, many mutations are novel (13 of the 30 BRCA1 mutations and 24 of the 44
      BRCA2). We report that while there were an equal proportion of BRCA1 and BRCA2
      mutations in the Chinese population in our study, there were significantly more
      BRCA2 mutations among the Malays. In addition, we show that the predictive power
      of the BOADICEA risk-prediction model and the Manchester Scoring System was
      significantly better for BRCA1 than BRCA2, but that the overall sensitivity,
      specificity and positive-predictive value was lower in this population than has
      been previously reported in Caucasian populations. CONCLUSION: Our study
      underscores the need for larger collaborative studies among non-Caucasian
      populations to validate the role of genetic testing and the use of risk
      prediction models in ensuring that the other populations in the world may also
      benefit from the genomics and genetics era.

PMID- 18627637
TI  - Correlates of preclinical cardiovascular disease in Indigenous and Non-Indigenous
      Australians: a case control study.
AB  - BACKGROUND: The high frequency of premature death from cardiovascular disease in
      indigenous Australians is often attributed to the high prevalence of risk
      factors, especially type II diabetes mellitus (DM). We evaluated the relationship
      of ethnicity to atherosclerotic burden, as evidenced by carotid intima-media
      thickness (IMT), independent of risk factor status. METHODS: We studied 227
      subjects (147 men; 50 +/- 13 y): 119 indigenous subjects with (IDM, n = 54), and
      without DM (InDM, n = 65), 108 Caucasian subjects with (CDM, n = 52), and without
      DM (CnDM, n = 56). IMT was measured according to standard methods and compared
      with clinical data and cardiovascular risk factors. RESULTS: In subjects both
      with and without DM, IMT was significantly greater in indigenous subjects. There
      were no significant differences in gender, body mass index (BMI), systolic blood
      pressure (SBP), or diastolic blood pressure (DBP) between any of the groups, and
      subjects with DM showed no difference in plasma HbA1c. Cardiovascular risk
      factors were significantly more prevalent in indigenous subjects. Nonetheless,
      ethnicity (beta = -0.34; p < 0.0001), age (beta = 0.48; p < 0.0001), and smoking
      (beta = 0.13; p < 0.007) were independent predictors of IMT in multiple linear
      regression models. CONCLUSION: Ethnicity appears to be an independent correlate
      of preclinical cardiovascular disease, even after correction for the high
      prevalence of cardiovascular risk factors in indigenous Australians. Standard
      approaches to control currently known risk factors are vital to reduce the burden
      of cardiovascular disease, but in themselves may be insufficient to fully address
      the high prevalence in this population.

PMID- 18627639
TI  - Daily rhythmicity of glycemia in four species of domestic animals under various
      feeding regimes.
AB  - Daily rhythmicity of physiological processes has been described for numerous
      variables in numerous species. A major source of this rhythmicity is a circadian
      pacemaker located in the mammalian hypothalamus, but very little is known about
      how the pacemaker generates the multiplicity of bodily rhythms. Research on rats
      has shown that the rhythm of blood glucose concentration is not a mere
      consequence of the rhythm of food ingestion, but is rather generated directly by
      the pacemaker. In this study, we investigated the rhythm of blood glucose
      concentration in four different species of domestic animals under four different
      feeding regimes. Our results suggest that, as in rats, the rhythm of blood
      glucose concentration is not a mere consequence of the rhythm of food ingestion
      in sheep and cattle. In dogs and horses, however, the rhythmicity of blood
      glucose concentration seems to be contingent on the presence of a feeding regime.

PMID- 18627638
TI  - Fetal size in the second trimester is associated with the duration of pregnancy,
      small fetuses having longer pregnancies.
AB  - BACKGROUND: Conventionally, the pregnancy duration is accepted to be 280-282
      days. Fetuses determined by ultrasound biometry to be small in early pregnancy,
      have an increased risk of premature birth. We speculate that the higher rate of
      preterm delivery in such small fetuses represents a pathological outcome not
      applicable to physiological pregnancies. Here we test the hypothesis that in low
      risk pregnancies fetal growth (expressed by fetal size in the second trimester)
      is itself a determinant for pregnancy duration with the slower growing fetuses
      having a longer pregnancy. METHODS: We analysed duration of gestation data for
      541 women who had a spontaneous delivery having previously been recruited to a
      cross-sectional study of 650 low-risk pregnancies. All had a regular menses and a
      known date of their last menstrual period (LMP). Subjects were examined using
      ultrasound to determine fetal head circumference (HC), abdominal circumference
      (AC) and femur length (FL) at 10-24 weeks of gestation. Length of the pregnancy
      was calculated from LMP, and birth weights were noted. The effect of fetal size
      at 10-24 weeks of gestation on pregnancy duration was assessed also when
      adjusting for the difference between LMP and ultrasound based fetal age. RESULTS:
      Small fetuses (z-score -2.5) at second trimester ultrasound scan had lower birth
      weights (p < 0.0001) and longer duration of pregnancy (p < 0.0001) than large
      fetuses (z-score +2.5): 289.6 days (95%CI 288.0 to 291.1) vs. 276.1 (95%CI 273.6
      to 278.4) for HC, 289.0 days (95%CI 287.4 to 290.6) vs. 276.9 days (95%CI 274.4
      to 279.2) for AC and 288.3 vs. 277.9 days (95%CI 275.6 to 280.1) for FL.
      Controlling for the difference between LMP and ultrasound dating (using HC
      measurement), the effect of fetal size on pregnancy length was reduced to half
      but was still present for AC and FL (comparing z-score -2.5 with +2.5, 286.6 vs.
      280.2 days, p = 0.004, and 286.0 vs. 280.9, p = 0.008, respectively). CONCLUSION:
      Fetal size in the second trimester is a determinant of birth weight and pregnancy
      duration, small fetuses having lower birth weights and longer pregnancies (up to
      13 days compared with large fetuses). Our results support a concept of
      individually assigned pregnancy duration according to growth rates rather than
      imposing a standard of 280-282 days on all pregnancies.

PMID- 18627640
TI  - Comparing different approach and avoidance models of learning and personality in
      the prediction of work, university, and leadership outcomes.
AB  - Jackson (2005) developed a hybrid model of personality and learning, known as the
      learning styles profiler (LSP) which was designed to span biological, socio
      cognitive, and experiential research foci of personality and learning research.
      The hybrid model argues that functional and dysfunctional learning outcomes can
      be best understood in terms of how cognitions and experiences control,
      discipline, and re-express the biologically based scale of sensation-seeking. In
      two studies with part-time workers undertaking tertiary education (N = 137 and
      58), established models of approach and avoidance from each of the three
      different research foci were compared with Jackson's hybrid model in their
      predictiveness of leadership, work, and university outcomes using self-report and
      supervisor ratings. Results showed that the hybrid model was generally optimal
      and, as hypothesized, that goal orientation was a mediator of sensation-seeking
      on outcomes (work performance, university performance, leader behaviours, and
      counterproductive work behaviour). Our studies suggest that the hybrid model has
      considerable promise as a predictor of work and educational outcomes as well as
      dysfunctional outcomes.

PMID- 18627641
TI  - Physician perception and recommendation of insulin pens for patients with type 2
      diabetes mellitus.
AB  - OBJECTIVE: To determine the way in which physicians perceive insulin pens and the
      factors that affect their recommendations and their patients' pen initiation/use.
      RESEARCH DESIGN AND METHODS: Primary care physicians ( N = 300; 108 family
      practice, 192 internal medicine) and endocrinologists (N = 225) were recruited
      from national databases (IMS and AMA) to participate in an Internet survey. All
      data are self-reports. Measures include five dependent variables (the extent of
      suitability for patient segments, two pen-related behaviors--their frequency of
      presenting patients with the pen as a treatment option and strength of pen
      recommendation--and extent of their patients' pen initiation and use) and several
      potential correlates: practice characteristics; therapeutic philosophy and
      practices; perceptions of insulin pens (convenience, facilitation of self-care,
      blood glucose control efficacy, cost/coverage). Correlates of dependent variables
      were examined using multiple linear regression. RESULTS: Significantly (p < 0.05)
      more patient pen use and/or successful pen initiation was reported by physicians
      who: (1) were more involved in clinical practice, were early adopters of clinical
      innovations or instructed their patients regarding insulin use; (2) reported less
      insulin mixing or therapeutic inertia; (3) perceived pens as efficacious and
      facilitating self-care; and (4) presented and recommended pens to their patients.
      More frequent presentation of pens to patients and/or stronger recommendation of
      pen use was reported by physicians who were early innovation adopters, reported
      less insulin mixing or therapeutic inertia, and perceived pens as convenient and
      efficacious (p < 0.05). LIMITATIONS: The study is a cross-sectional survey using
      a self-administered questionnaire yielding unverified self-reports. Physicians
      treating few patients with diabetes mellitus or prescribing no insulin were
      excluded from the study. CONCLUSIONS: Physicians' pen-related actions are a
      function of their personal and practice characteristics as well as their
      perceptions of pens. Physicians' presentation of pens as an option is strongly
      associated with perceived pen convenience, but physicians' pen recommendations
      and the estimated pen use/initiation of their patients are most strongly
      associated with the perception of clinically relevant pen attributes--glucose
      control efficacy and/or self-care facilitation.

PMID- 18627642
TI  - 24-hour control of intraocular pressure with 2% dorzolamide/0.5% timolol fixed
      combination ophthalmic solution in open-angle glaucoma.
AB  - OBJECTIVE: To evaluate the 24-hour efficacy and tolerability of 2%
      dorzolamide/0.5% timolol fixed combination (DTFC) solution in open-angle glaucoma
      and ocular hypertension. RESEARCH DESIGN AND METHODS: Randomized, parallel,
      double-masked, multicenter study. Patients with insufficiently controlled
      intraocular pressure (IOP > or = 22 mmHg) were randomized to DTFC (N = 117) or
      timolol (N = 115). IOP was measured at baseline, 6 weeks, and 8 weeks, with
      measurements taken at 6 p.m., 8 p.m., 10 p.m., 2 a.m., 6 a.m., 8 a.m., 10 a.m.,
      and 2 p.m. ClinicalTrials. gov identifier: NCT00108017 MAIN OUTCOME MEASURES:
      Statistically significant change in IOP from untreated baseline for DTFC at all
      hours at week 8. Secondary outcome measures included: IOP-lowering at week 6 at
      all individual time points, change from baseline to 8 weeks in mean daytime IOP
      (average of 8 a.m., 10 a.m., 2 p.m., 6 p.m., and 8 p.m. IOPs) and night-time IOP
      (10 p.m., 2 a.m., 6 a.m.), and comparison of DTFC with timolol after 8 weeks.
      RESULTS: Patients receiving DTFC had a statistically significant and clinically
      relevant reduction in IOP at week 8 compared with baseline at all eight time
      points (p < 0.001). Significant IOP reductions were also seen at all time points
      at week 6 (p < 0.001). DTFC significantly lowered mean daytime IOP and night-time
      IOP ( p < 0.001 for both). Timolol alone also significantly reduced IOP from
      baseline at 8 weeks for all diurnal time points, and mean daytime and night-time
      IOP ( p < 0.001 for all). Compared with timolol alone, there were significantly
      greater reductions with DTFC at 10 a. m. (p = 0.003) and 2 p. m. (p = 0.016), and
      for mean daytime IOP (p = 0.025) at 8 weeks. Significant between-treatment
      differences were not observed at other time points. Both treatments were well
      tolerated, with no differences observed in the safety profiles between the
      treatment groups. CONCLUSIONS: Both DTFC and timolol provided significant IOP
      reduction over the entire 24-hour measurement period. Although this study was not
      designed or powered to compare DTFC and timolol, DTFC exhibited greater IOP
      lowering than timolol during the daytime, but not at night.

PMID- 18627644
TI  - Colon cancer screening methods-how low do they go?

PMID- 18627643
TI  - Are there too many practice guidelines for acute pancreatitis?

PMID- 18627645
TI  - The best view of Barrett's esophagus.

PMID- 18627646
TI  - Genes and irritable bowel syndrome: is there a link?
AB  - Advances in genetics and genomics during the past decade, including sequencing of
      the human genome and DNA sequencing technologies, have made it possible to
      discover the genetic basis for many diseases. With the discovery of multiple
      genetic loci for gastrointestinal diseases such as Crohn's disease, some have
      begun to wonder-Could there be a genetic basis for irritable bowel syndrome
      (IBS)? This article summarizes the evidence for and against a link between genes
      and IBS. In addition, a gene-environment paradigm is presented to combine the two
      opposing hypotheses, as IBS may represent a complex genetic disorder that results
      from the interaction of several genes and environmental risk factors.

PMID- 18627647
TI  - The role of serotonin in irritable bowel syndrome: implications for management.
AB  - Irritable bowel syndrome (IBS) is a poorly understood, common, chronic condition
      characterized by -abdominal discomfort associated with altered bowel habits in
      the absence of structural or biochemical abnormalities. Despite the significant
      economic and personal burden associated with IBS, treatment options remain
      limited. Serotonin is recognized as a key neurotransmitter in intestinal
      secretory, sensory, and motor function. Although the pathophysiology of IBS is
      incompletely understood, there is evidence that abnormalities in brain-gut
      signaling and serotonin metabolism play a role. This article reviews the evidence
      that serotonin, one of the better-understood neurotransmitters with respect to
      its role in human central and intestinal physiology, plays a role in IBS.
      Serotonin signaling is discussed, with a focus on receptor subtypes and the
      therapeutic agents that target these receptors. Evidence that IBS is associated
      with perturbations in serotonin metabolism at various steps in the signaling
      pathway is also addressed, along with the limitations on alteration in serotonin
      metabolism as the sole explanation for the constellation of symptoms observed in
      patients with IBS.

PMID- 18627648
TI  - Novel techniques to study visceral hypersensitivity in irritable bowel syndrome.
AB  - Visceral hypersensitivity has emerged as a key hypothesis in explaining the
      painful symptoms of irritable bowel syndrome (IBS), and it has been proposed as a
      "biologic marker" for the condition. Visceral hypersensitivity can be influenced
      by peripheral and central mechanisms affecting pain perception. The optimal
      method for its assessment in humans has not been determined. Current techniques
      include stimulation via the computerized barostat and electrical stimulation,
      response measures including the lower limb reflex, and brain imaging modalities
      such as functional MRI and positron emission tomography. It has been shown that
      IBS patients have decreased sensory thresholds to colonic and rectal balloon
      distention by barostat. Studies using electrical stimulation and the RIII lower
      limb reflex have further confirmed enhanced visceral perception in IBS. Evidence
      from more recent neuro-imaging studies suggests that IBS patients have abnormal
      activation of brain circuits involved in emotional and cognitive modulation of
      sensory information, resulting in ineffective pain modulation; these circuits may
      have a pathophysiologic role in enhancing visceral perception. There are few
      effective pharmacologic treatments that relieve IBS symptoms, and improved
      understanding of brain-gut interactions and factors relating to enhanced visceral
      perception may guide us in developing more efficacious treatments.

PMID- 18627649
TI  - What is the evidence for the use of probiotics in functional disorders?
AB  - A rationale for the use of probiotics for a number of functional gastrointestinal
      symptoms and syndromes can be developed, and an experimental basis for their use
      continues to emerge, but data from well-conducted clinical trials of probiotics
      in this area remain scarce. Irritable bowel syndrome (IBS) has attracted the most
      attention; recent revelations regarding the potential pathogenic roles of the
      enteric flora and immune activation have led to reawakened interest in bacterio
      therapy for this common and challenging disorder. Some recent randomized,
      controlled studies attest to the efficacy of some probiotics in alleviating
      individual IBS symptoms, and selected strains have a more global impact. Evidence
      for long-term efficacy is also beginning to emerge, though more studies are
      needed in this regard. In other functional syndromes, data are far from adequate
      to make recommendations, but there is evidence for efficacy of probiotics in
      treating individual symptoms such as diarrhea, constipation, and bloating. The
      interpretation of much of the literature in this area is complicated by lack of
      quality control, use of many different species and strains, and, above all,
      significant deficiencies in trial methodology.

PMID- 18627651
TI  - Studying the human microbiome: beyond the petri dish.

PMID- 18627650
TI  - Is irritable bowel syndrome an inflammatory disorder?
AB  - Histopathologic data demonstrate low-grade mucosal inflammation in a subset of
      patients with irritable bowel syndrome (IBS). This inflammatory infiltrate is
      mainly represented by increased numbers of T lymphocytes and mast cells lying in
      the lamina propria. The close apposition of immunocytes to gut nerves supplying
      the mucosa provides a basis for neuroimmune cross-talk, which may explain gut
      sensorimotor dysfunction and related symptoms in patients with IBS. A previous
      gastroenteritis (due to Campylobacter jejuni, Salmonella, Shigella, Escherichia
      coli, and, likely, viruses) is now an established etiologic factor for IBS
      (hence, postinfectious IBS). Other putative causes, such as undiagnosed food
      allergies, genetic abnormalities, stress, or bile acid malabsorption, may also
      promote and maintain a low-grade mucosal inflammation in IBS. The identification
      of mucosal inflammation in IBS has pathophysiologic implications and paves the
      way for novel therapeutic options.

PMID- 18627652
TI  - Traveler's diarrhea: what is the best regimen?

PMID- 18627653
TI  - The human gut microbiome: implications for future health care.
AB  - In their intestine, humans possess an "extended genome" of millions of microbial
      genes-the microbiome. Because this complex symbiosis influences host metabolism,
      physiology, and gene expression, it has been proposed that humans are complex
      biologic "superorganisms." Advances in microbiologic analysis and systems biology
      are now beginning to implicate the gut microbiome in the etiology of localized
      intestinal diseases such as the irritable bowel syndrome, inflammatory bowel
      disease, and colon cancer. These approaches also suggest possible links between
      the gut and previously unassociated systemic conditions such as type 2 diabetes
      and obesity. The elucidation of the intestinal microbiome is therefore likely to
      underpin future disease prevention strategies, personalized health care regimens,
      and the development of novel therapeutic interventions. This review summarizes
      the research that is defining our understanding of the intestinal microbiome and
      highlights future areas of research in gastroenterology and human health in which
      the intestinal microbiome will play a significant role.

PMID- 18627654
TI  - Clostridium difficile infection: emerging concepts and treatments.
AB  - Clostridium difficile infection has become one of the most common causes of
      diarrhea in patients frequenting hospitals, skilled nursing facilities, and
      physicians' offices. Although the pathogenesis and clinical description were well
      elucidated three decades ago, cure during the initial episode now occurs in fewer
      than two thirds of patients exhibiting clinical illness. The past decade has
      brought a new strain with more toxin. Frequent relapses in elderly patients are
      now the norm rather than a rarity. This review is intended to update clinicians
      regarding diagnosis, infection control, and treatment, including treatment of the
      difficult-to-treat patient with multiple relapses of C. difficile infection.

PMID- 18627655
TI  - Gastrointestinal cytomegalovirus disease in the immunocompromised patient.
AB  - Cytomegalovirus (CMV) has emerged as a significant opportunistic pathogen in the
      era of immunosuppression. CMV was a common cause of gastrointestinal disease in
      AIDS patients, but the introduction of highly active antiretroviral therapy has
      led to a dramatic decline in AIDS-related disease. Among patients with solid
      organ transplants, CMV has become an increasingly important cause of
      gastrointestinal disease as more routine use of early CMV prophylaxis has
      increased delayed-onset disease, which is often tissue invasive at presentation.
      The role of CMV in inflammatory bowel disease is controversial; treatment may be
      indicated in selected cases of steroid-refractory disease with evidence of CMV.
      Diagnosis of gastrointestinal CMV disease generally requires endoscopic biopsy
      with histologic confirmation. CMV culture of biopsy material may be falsely
      positive because of contamination from latently infected cells. The standard
      induction treatment of gastrointestinal CMV disease uses intravenous ganciclovir,
      though the use of oral valganciclovir is increasing, especially for long-term
      maintenance or suppression therapy.

PMID- 18627656
TI  - Herpes simplex virus and the alimentary tract.
AB  - Herpes simplex virus (HSV) infection is well known as a sexually transmitted
      disease. However, relatively little has been published concerning the
      presentations and treatment of HSV infection within the gastrointestinal tract,
      where HSV most commonly affects the esophagus in both immunocompromised and
      immunocompetent patients. HSV proctitis is not uncommon and occurs primarily in
      males having sex with males. In patients with normal immune systems,
      gastrointestinal HSV infections are generally self-limited and rarely require
      antiviral therapy. Treatment of infection is suggested for immunocompromised
      patients, though no large randomized controlled trials have been performed. This
      article reviews the manifestations of HSV infection within the luminal
      gastrointestinal tract and options for diagnosis and treatment.

PMID- 18627657
TI  - Salmonellosis and the gastrointestinal tract: more than just peanut butter.
AB  - Nontyphoidal salmonellosis is the leading cause of foodborne illness in the
      United States, causing about 1.4 million infections annually. Most cases of
      salmonellosis are due to ingestion of contaminated food items such as eggs, dairy
      products, and meats, but almost any foodstuff can be implicated, including peanut
      butter, as seen during a recent outbreak of more than 600 Salmonella infections.
      Although outbreaks often gain national media attention, the majority of
      nontyphoidal Salmonella infections in the United States occur sporadically. Risk
      factors for salmonellosis include gastric hypoacidity, recent use of antibiotics,
      extremes of age, and immunosuppressive conditions. Clinical manifestations of the
      infection most commonly involve self-limited gastroenteritis, but bacteremia and
      endovascular and localized infections may occur. Most cases of gastrointestinal
      involvement are self-limited, and antibiotic therapy is reserved for persons at
      risk for complicated disease. Preventive strategies by both industry and
      consumers are advocated to further reduce the occurrence of nontyphoidal
      salmonellosis.

PMID- 18627658
TI  - Evaluation and treatment of the patient coinfected with hepatitis B and HIV.
AB  - Hepatitis B virus (HBV) is a common coinfection in HIV-infected patients, and
      significant liver disease and mortality occur as the result of this disease
      combination. Potent anti-HBV therapy is available and can be used to improve
      outcomes by suppressing HBV DNA. Many HBV agents have dual activity with HIV and
      may be used to treat both diseases. However, care must be taken when using HBV
      nucleos(t)ides that have not been fully studied in the HIV-infected population
      because the emergence of strains resistant to HIV treatment has been reported.
      Careful monitoring of response to treatment is needed when treating an HIV/HBV
      patient with severe immune suppression. Improved ability to obtain long-term HBV
      DNA suppression and avoid resistance will translate into improved survival in
      this population.

PMID- 18627659
TI  - Update on PML: lessons from the HIV uninfected and new insights in pathogenesis
      and treatment.
AB  - Significant advances in our understanding of progressive multifocal
      leukoencephalopathy (PML) and its causative agent, JC virus, have been made since
      PML was first described 50 years ago. However, immune reconstitution remains the
      only proven, effective therapy in this devastating central nervous system
      disorder. Early diagnosis and adjustments of immune suppressants and modulator
      agents are critical in managing PML in HIV-negative patients. This review
      summarizes recent advances in our understanding of PML in HIV-uninfected patients
      in oncology, rheumatology, organ transplantation, and idiopathic immune
      deficiency and in association with novel therapeutics. Brain MRI data from our
      case series of brain biopsy-proven HIV-negative PML patients indicate the
      presence of an inflammatory/immune reaction in brain tissues, which was confirmed
      by immunocytologic analysis. Future studies to better understand PML pathogenesis
      in HIV-negative individuals may help uncover new potential therapeutic targets
      and improve PML outcomes.

PMID- 18627660
TI  - Ocular complications of HIV infection in sub-Sahara Africa.
AB  - This article reviews the magnitude and spectrum of ocular complications of HIV
      infection in sub-Sahara Africa. A literature search was done using PubMed,
      Google, and UpToDate and by talking to ophthalmologists and HIV experts working
      in the region. Ocular complications of HIV infection, mostly retinal, are seen in
      29% to 71% of patients. Cytomegalovirus retinitis affects 0% to 16.5% of HIV
      infected patients and is treated successfully with intravitreal ganciclovir in
      South Africa and Botswana. Ocular surface squamous neoplasia is seen in 4% to
      7.8% of persons with HIV (a 5%-6% increase in Uganda and Tanzania), and
      recurrence after surgery occurs in 3.2% to 31.2%. In Zimbabwe, 45% of meningitis
      in adults is cryptococcal, and cryptococcal meningitis is the third leading cause
      of death in HIV patients in rural Uganda. In Rwanda, 9% of patients with
      cryptococcal meningitis developed visual loss and sixth nerve palsy. Thus, HIV
      infection leads to significant ocular morbidity in sub-Sahara Africa.

PMID- 18627661
TI  - Oral HPV complications in HIV-infected patients.
AB  - Human papillomavirus (HPV) infection and disease, including that of the oral
      cavity, has not dramatically declined since the introduction of potent
      combination therapy to control HIV. Two manifestations of HPV in the oral cavity
      that may be on the rise are HPV-32-associated oral warts and HPV-16-associated
      oral cancers. A current research focus is the natural history of HPV infections
      in the oral cavity. A better understanding of the natural history of oral HPV
      infections could lead to improved diagnosis and treatment for oral HPV
      complications in HIV-positive patients.

PMID- 18627662
TI  - Managing tuberculosis and HIV in sub-Sahara Africa.
AB  - Tuberculosis (TB) and HIV represent a deadly duo in sub-Sahara Africa, a region
      most affected by both diseases. The HIV epidemic has aggravated already strained
      and frequently poorly performing TB control programs. These programs face
      numerous challenges, and novel, regionally appropriate solutions need to be
      developed. In the context of TB, some challenges include the rapid diagnosis of
      active TB in the face of paucibacillary lung disease and atypical presentations
      with HIV/AIDS, lack of clinical expertise, poor contact tracing, limited
      laboratory facilities, delayed recognition of drug-resistant TB, increased
      workload of health care workers, erratic drug supplies, inadequate isolation
      facilities, and environmental and personal protection in drug-resistant cases.
      Similar problems exist in the context of HIV but are aggravated by the need for
      complex antiretroviral drug regimens and lifelong treatment. Treating both
      conditions invites drug interactions and toxic effects that are common to both
      HIV and TB treatment and the vexing question of when to introduce antiretroviral
      treatment in subjects with active TB. Combining HIV and TB care has the potential
      to bring additional infrastructural and human resources to the respective
      programs, with synergistic benefits.

PMID- 18627663
TI  - Non-AIDS-defining malignancies among HIV-infected patients in the highly active
      antiretroviral therapy era.
AB  - In the highly active antiretroviral therapy (HAART) era, the incidence of AIDS
      defining malignancies (ADMs) has declined significantly. On the other hand, the
      incidence of other malignancies not known to be associated with immunosuppression
      (non-ADMs) has not changed and remains significantly higher than in the general
      population. Some recent controlled studies even suggest that the incidence of
      selected non-ADMs has increased in the HAART era. These trends warrant a high
      index of suspicion for malignancies among HIV care providers and a renewed focus
      on understanding the mechanisms underlying the increased rates. Potential
      explanations for the higher non-ADM rates include longer survival of patients
      with HIV on HAART, with only partial immune recovery achieved in most patients;
      high incidence of human papillomavirus, Epstein-Barr virus, and hepatitis C virus
      coinfection in patients with HIV infection; and potential oncogenicity of long
      term HIV infection or of long-term HAART.

PMID- 18627664
TI  - The aging of the HIV epidemic.
AB  - Since the advent of highly active antiretroviral therapy, life expectancies for
      persons with HIV infection are similar to those for uninfected people. A growing
      proportion of HIV-infected individuals are now over the age of 50. We are also
      seeing an increase in the incidence of HIV infection in older adults. To meet the
      challenges of the ongoing HIV epidemic, prevention efforts should include a focus
      on older adults. Also, HIV care providers must address the many comorbidities
      that are common in the aging population. Additional research will clarify how the
      processes of aging and HIV infection overlap and interact. This review addresses
      many of these important considerations.

PMID- 18627666
TI  - Pharmacotherapy of anxious depression.

PMID- 18627665
TI  - Classification of anxiety disorders: dimensional assessments, intermediate
      phenotypes, and psychobiological bases.

PMID- 18627667
TI  - Recent advances in compulsive hoarding.
AB  - Compulsive hoarding is a common and often disabling neuropsychiatric disorder.
      This article reviews the conceptualization, phenomenology, diagnosis, etiology,
      neurobiology, and treatment of compulsive hoarding. Compulsive hoarding is part
      of a discrete clinical syndrome that includes difficulty discarding, urges to
      save, excessive acquisition, indecisiveness, perfectionism, procrastination,
      disorganization, and avoidance. It was thought to be part of obsessive-compulsive
      disorder or obsessive-compulsive personality disorder, but recent evidence
      indicates that it should be classified as a separate disorder with its own
      diagnostic criteria. Compulsive hoarding is a genetically discrete, strongly
      heritable phenotype. Neuroimaging and neuropsychological studies are elucidating
      its neurobiology, implicating dysfunction of ventral and medial prefrontal
      cortical areas that mediate decision-making, attention, and emotional regulation.
      Effective treatments include pharmacotherapy and cognitive-behavioral therapy.
      More research will be required to determine the prevalence, etiology, and
      pathophysiology of compulsive hoarding and to develop better treatments.

PMID- 18627668
TI  - Social support and resilience to stress across the life span: a neurobiologic
      framework.
AB  - This review discusses selected neurobiologic and genetic factors-including
      noradrenergic and hypothalamic-pituitary-adrenal axis markers, oxytocin pathways,
      and serotonin transporter and brain-derived neurotrophic factor gene
      polymorphisms-in the context of resilience to stress, with an emphasis on social
      support. Social support's impact on medical and psychiatric health outcomes is
      reviewed, and putative mediators are discussed. The reviewed literature indicates
      that social support is exceptionally important to maintaining good physical and
      psychological health in the presence of genetic, developmental, and other
      environmental risks. Future studies should continue to explore the neurobiologic
      factors associated with social support's contribution to stress resilience.

PMID- 18627669
TI  - Advances in understanding illness anxiety.
AB  - Illness anxiety, also known in its more severe form as hypochondriasis, is a
      debilitating and chronic condition in which normal bodily symptoms are
      misinterpreted as signs of serious medical illness. Patients suffer with the fear
      that they are ill despite reassurance to the contrary and often overuse medical
      services in the process. This article critically evaluates the recent literature
      on illness anxiety and related, medically unexplained symptoms, highlighting new
      and interesting findings in the areas of prevalence, classification/diagnosis,
      management, and evidence-based treatment and new frontiers in understanding
      illness anxiety, such as brain imaging, neuroimmunology, and cyberchondria.

PMID- 18627670
TI  - Comorbidity of pain and anxiety disorders.
AB  - The comorbidity of anxiety disorders with pain has received little research
      attention even though recent studies show that these disorders are as likely to
      co-occur with chronic pain conditions as depressive disorder. Comorbid anxiety
      has implications for the impact and outcome of pain conditions. Even though it
      may be intuitively plausible to suppose that the anxiety occurs in the context of
      a preexisting pain condition, there is evidence for a reverse causal link and
      shared risk factors, including distal events occurring in childhood.

PMID- 18627671
TI  - Emerging treatments for Tourette's disorder.
AB  - Tourette's disorder is a childhood-onset neuropsychiatric disorder characterized
      by multiple motor and vocal tics. Many children with Tourette's disorder improve
      throughout adolescence. However, some adults with Tourette's disorder still
      experience severe symptoms and significant disability. This article examines the
      evidence base for current treatments for Tourette's disorder. Emerging treatments
      such as deep brain stimulation, habit reversal therapy, and repetitive trans
      cranial magnetic stimulation are also discussed.

PMID- 18627672
TI  - Anxiety disorders in pregnancy.
AB  - There is now growing realization that many women suffer from new onset or
      worsening of anxiety disorders during pregnancy. Studies of anxiety symptoms in
      pregnancy show that a significant portion of women are affected. Anxiety symptoms
      in pregnancy have been associated with adverse fetal and infant outcomes.
      Furthermore, having an anxiety disorder during pregnancy is one of the strongest
      risk factors for postnatal depression. Although the literature on treating
      anxiety disorders in pregnancy per se is sparse, response to standard treatment
      is good. The risk of teratogenicity with pharmacotherapy must be considered, but
      it can be minimized by judicious tapering and cessation of medication during high
      risk periods.

PMID- 18627673
TI  - Schizophrenia: from genes to phenes to disease.
AB  - This article provides an overview of the past year's literature on schizophrenia
      genetics. Quantitative genetics continues to be an important foundation in which
      family and twin studies have been used to evaluate potential endophenotypes.
      Research in molecular genetics has focused on detecting multiple genes of small
      effect, and developments relating to key positional and functional candidate
      genes are reviewed. Large-scale, multicenter studies are proving to be important
      in this quest. Research using neuroimaging and animal modeling studies continues
      to link genotype with phenotype. It is increasingly apparent that some candidate
      genes considered important in schizophrenia are likely to be relevant to the
      etiology of other psychotic disorders, including bipolar disorder. This notion
      may challenge traditional disease classifications, not only in research but
      potentially in clinical practice.

PMID- 18627674
TI  - Toward defining schizophrenia as a more useful clinical concept.
AB  - Delineating schizophrenia remains elusive despite considerable interest and study
      for more than a century. During this time, a variety of terms and defining
      features have been ascribed to the construct. The predominant contemporary
      construct, for which substantial limitations persist, has changed little in the
      past 30 years. With the approaching arrival of the DSM-V, interest in the
      nosology of schizophrenia has rebounded. Recent publications have focused
      principally on the following: integrating dimensional approaches to diagnosis,
      subtypes of schizophrenia, endophenotypes, and identifying those at early risk as
      part of a staging process. Some have even suggested replacing the term. Although
      an etiopathic diagnosis remains out of reach, contemporary research is marching
      down several distinct paths toward defining schizophrenia as a construct of
      greater clinical utility.

PMID- 18627675
TI  - Better pharmacotherapy for schizophrenia: what does the future hold?
AB  - Despite the expansion of available antipsychotic drugs over the past 50 years,
      functional outcomes for individuals with schizophrenia have not markedly
      improved. These agents are efficacious for psychosis but do not adequately
      address other core domains of schizophrenia psychopathology, namely negative
      symptoms and cognitive impairment, which have a greater impact on functional
      outcomes, including vocational or academic performance and interpersonal
      relationships. In addition, treatment-refractory psychosis still precludes
      functional improvement in many patients. Schizophrenia is a clinical syndrome
      consisting of these domains, which likely have some disparities in their
      respective pathophysiologies. This suggests that drug development should look to
      other molecular targets besides the D2 receptor, which characterizes the
      mechanism of available medications for schizophrenia. In this report, we review
      novel pharmacologic approaches that aim to specifically address each individual
      domain of schizophrenia. The goal of this future pharmacotherapy strategy is to
      advance outcomes beyond psychosis remission and toward functional recovery.

PMID- 18627677
TI  - Formaldehyde, aspartame, and migraines: a possible connection.
AB  - Aspartame is a widely used artificial sweetener that has been linked to pediatric
      and adolescent migraines. Upon ingestion, aspartame is broken, converted, and
      oxidized into formaldehyde in various tissues. We present the first case series
      of aspartame-associated migraines related to clinically relevant positive
      reactions to formaldehyde on patch testing.

PMID- 18627676
TI  - Tactics and technologies to manage nonadherence in patients with schizophrenia.
AB  - The occurrence of treatment nonadherence among patients with schizophrenia is
      clinically significant. However, studies show that clinicians do not make
      systematic efforts to identify and monitor it over time. This paper reviews the
      various tactics for identifying and monitoring adherence behavior. A
      comprehensive review of published studies comparing typical and atypical
      antipsychotics in terms of medication adherence yields mixed results at best.
      Changing forces in the delivery of health care in the United States will promote
      efforts to improve the recognition of nonadherence in patients with schizophrenia
      and develop strategies and tactics to decrease the current rates of nonadherence.
      Such tactics are described in this paper, and emerging best practices are
      identified. Ultimately, if nonadherence rates are to decrease, it will be
      necessary to align the incentives of the treater and the treated.

PMID- 18627678
TI  - Neem oil: an herbal therapy for alopecia causes dermatitis.
AB  - For more than 2,000 years, the neem tree has been considered one of the most
      useful and versatile plants in the world. Neem oil has been used for both
      homeopathic remedies and as a pesticide. Both systemic and contact reactions have
      occurred with the use of neem oil. We report a patient who presented with an
      acute case of contact dermatitis on the scalp and face after the use of neem oil
      for alopecia and present a review of the literature regarding its uses, toxicity,
      and regulation.

PMID- 18627679
TI  - The Asteraceae family of allergens.

PMID- 18627680
TI  - Tosylamide formaldehyde resin.

PMID- 18627681
TI  - para-Phenylenediamine.

PMID- 18627683
TI  - Atopic dermatitis, patch testing, and house dust mites: a brief review.
AB  - The association between house dust mites (HDMs) and atopic dermatitis (AD) has
      long been a contested issue in both dermatology and allergy/immunology. As AD
      continues to burden millions of individuals and even whole societies, the
      commercial availability of a HDM allergen mix for epicutaneous testing has
      revived efforts to identify a definitive link between HDMs and AD. Conclusive
      evidence of a role for HDMs in the pathogenesis of AD would justify patch testing
      with mite allergens and would further the use of allergen-specific immunotherapy
      in the management of such patients; an absence of involvement would refocus our
      investigative efforts on other conspirators. We present a thorough review of the
      dissenting scientific evidence and expert opinions on this controversial topic.
      The association of HDMs with AD has remained elusive, and additional
      investigation is necessary to resolve this vexing riddle.

PMID- 18627684
TI  - North American Contact Dermatitis Group patch-test results, 2003-2004 study
      period.
AB  - BACKGROUND: Allergic contact dermatitis is a significant cause of both
      occupational and non-occupational skin disease. Patch testing is an important
      diagnostic tool for the determination of responsible allergens. OBJECTIVE: This
      study reports the results of patch testing by the North American Contact
      Dermatitis Group from January 1, 2003, to December 31, 2004. METHODS: At 13
      centers in North America, patients were tested with the same screening series of
      65 allergens, with a standardized patch-testing technique. Data were recorded on
      standardized forms and manually verified and entered. Descriptive frequencies
      were calculated, and trends were analyzed with chi-square statistics. RESULTS: A
      total of 5,148 patients were tested. Of these, 3,432 (66.7%) had at least one
      positive reaction, 2,284 (44.4%) were ultimately determined to have primary
      allergic contact dermatitis, and 676 (13.1%) had occupation-related skin disease.
      There were 9,762 positive allergic reactions. Compared to the previous reporting
      period (2001-2002), allergies to nickel, budesonide, mercaptobenzothiazole, and
      paraben mix were at least 1.12 times more common (all p values < .03). Compared
      with the previous 8 years (1994-2002), only the prevalence rates of allergies to
      nickel and budesonide were statistically significantly higher (p values < .003).
      CONCLUSION: Allergic contact dermatitis from nickel and budesonide may be
      increasing in North America. These results again underscore the value of patch
      testing with many allergens.

PMID- 18627685
TI  - Use of the North American Contact Dermatitis Group Standard 65-allergen series
      alone in the evaluation of allergic contact dermatitis: a series of 794 patients.
AB  - BACKGROUND: The "gold standard" for diagnosing allergic contact dermatitis is
      patch testing. Previous studies have not adequately addressed the validity and
      usefulness of the North American Contact Dermatitis Group (NACDG) Standard 65
      allergen series alone as a screening tool in the evaluation of contact
      dermatitis. OBJECTIVE: The purpose of this study is to examine the usefulness of
      the NACDG series of 65 allergens as an exclusive screening method in the
      diagnosis of contact allergy. METHODS: A retrospective chart review of 794
      patients referred for patch testing with the NACDG Screening Series with or
      without additional allergens was performed to determine the number of positive
      patch-test results. The study groups were analyzed to identify whether the
      positive reactions were to allergens in the NACDG Standard Series or to allergens
      in the supplementary group. RESULTS: Of the 794 patients patch-tested between
      July 1, 2004, and July 1, 2006, 590 (74.31%) had a positive reaction to either an
      NACDG patch-tested allergen or a supplemental allergen; 386 (65.42%) patients
      testing positive for an allergen were positive to an NACDG allergen only, and 534
      (90.51%) of the total positive reactors were positive for at least one NACDG test
      allergen. CONCLUSION: As a screening tool, the NACDG Standard Series is
      substantially more efficacious than are more limited standard series when used
      exclusively in the evaluation of patients with allergic contact dermatitis. More
      extensive testing, including testing with suspected supplementary allergens
      determined by thorough history and physical examination, can improve upon the
      NACDG series as a means to investigate the full causes of contact dermatitis in
      any individual patient.

PMID- 18627686
TI  - Prevalence of allergic contact dermatitis in Thailand.
AB  - BACKGROUND: Contact dermatitis is a universal condition. Patch testing is an
      effective diagnostic tool for clinically suspected allergic contact dermatitis.
      Previous studies have shown that the prevalence of specific allergens varies by
      geographic area. OBJECTIVE: To determine the relative frequency of positive
      reactions to different sensitizers in Thai patients with clinically suspected
      contact dermatitis. METHODS: The results of patch tests performed from January 1,
      2004, to December 31, 2006, at the Siriraj Hospital Contact Dermatitis Clinic
      were analyzed. A total of 323 consecutive patients (83% women and 17% men, with
      mean age of 39 years) were patch-tested with the total number of allergens used
      from both European standard patch test series and International patch test series
      was 26. RESULTS: The most frequent allergen was potassium dichromate (27%),
      followed by nickel sulfate (26.6%), fragrance mix (20.7%), and cobalt chloride
      (16.4%). CONCLUSIONS: We compared the results with published findings in Asian
      Pacific populations to identify geographic cultural differences in the prevalence
      of the allergens. The findings of the present study are able to identify the set
      of prominent local allergens for better revision of the standard patch test to
      local needs.

PMID- 18627687
TI  - Positive patch-test reactions to platinum are rare.
AB  - BACKGROUND: Although contact allergy to some metals is common, patch testing for
      allergy to platinum is rarely performed. OBJECTIVE: To determine the prevalence
      of positive patch-test reactions to platinum in an unselected consecutive group
      of patients presenting for diagnostic patch testing. METHODS: Unselected patients
      who presented with a possible diagnosis of contact dermatitis were tested with a
      series of allergens, including ammonium tetrachloroplatinate 0.25% aqueous.
      RESULTS: Of 446 patients tested, only 2 females showed positive reactions to
      platinum; one had no other positive reactions, and the other had reactions to
      other metals. CONCLUSIONS: Positive patch-test reactions to platinum are rare.
      However, platinum jewelry may occasionally provoke allergic contact dermatitis.

PMID- 18627688
TI  - Allergic contact dermatitis as a complication of lid loading with gold implants.
AB  - Paralysis of the orbicularis oculi muscle in patients with a facial nerve injury
      causes functional and cosmetic disabilities including inability to close the
      eyelid. This complication is often treated by implanting a gold weight in the
      upper eyelid, which, however, is not without side effects. Four patients are
      described who, after lid loading with a gold implant, acquired an inflammatory
      reaction due to contact allergy to the metal inserted. The allergy was
      demonstrated by patch testing with gold sodium thiosulfate. The implant was
      removed and the dermatitis resolved. Contact allergy to gold occurs frequently
      and may explain many cases of complications to lid loading with the metal.

PMID- 18627689
TI  - Contact allergy from vitamins in cosmetic products.
AB  - We report three new cases of allergic contact dermatitis due to vitamins in
      cosmetic creams. The first patient was diagnosed with worsening rosacea but had
      allergic contact dermatitis from alpha-tocopherol in a moisturizing cream. The
      second and third cases presented as acute eyelid dermatitis due to vitamin K in
      eyelid lifter creams. Repeated open application testing and patch tests with the
      actual products and individual components of the creams were useful in
      establishing the diagnosis.

PMID- 18627690
TI  - Cocamidopropyl betaine.
AB  - Cocamidopropyl betaine (CAPB) is an amphoteric synthetic detergent that has been
      increasingly used in cosmetics and personal hygiene products (eg, shampoos,
      contact lens solutions, toothpaste detergents, makeup removers, bath gels, skin
      care products, cleansers, liquid soaps, antiseptics, and gynecologic and anal
      hygiene products) because it induces relatively mild skin irritation. Delayed T
      cell-mediated type IV hypersensitivity reactions to CAPB have been reported, and
      contact sensitization prevalence is estimated at between 3.0 and 7.2%. The
      increasing rates of sensitization led to CAPB's being named Allergen of the Year
      in 2004. Related impurities rendered during the manufacturing process (such as
      amidoamine and dimethylaminopropylamine) are thought to play a role in
      sensitization.

PMID- 18627691
TI  - Treatment of hand dermatitis with alefacept.

PMID- 18627692
TI  - Disseminated allergic contact dermatitis after exposure to a topical medication
      containing geraniol.

PMID- 18627694
TI  - Leprosy: ongoing medical and social struggle in Vietnam.
AB  - BACKGROUND: Until recently, leprosy had been prominent in 33 countries worldwide,
      and Vietnam was ranked among the top 14 endemic countries. OBJECTIVE: The leprosy
      situation in Vietnam was reviewed as a sample of the worldwide ongoing medical
      and social struggle to assess the need for continued support for leprosy control
      activities and for social programs of integration of leprosy victims into the
      community. METHODS: A search was conducted of official Vietnamese publications,
      World Health Organization documents, major electronic databases, and popular
      leprosy Web sites; as well, notes from visits to local leprosy clinics and
      interviews with health workers were checked. RESULTS: Important achievements were
      realized through national determination and international collaboration. In
      contrast with the impressive performance statistics at the national level, and
      despite strong government efforts for leprosy control, the results obtained at
      the province-city and district-commune levels still exhibit deficiencies in case
      detection, treatment, and socioeconomic integration of leprosy victims.
      CONCLUSION: The struggle to eliminate such a complex and destructive infectious
      disease as leprosy does not end with the cure. Deep-seated medical and social
      problems remain. These problems are best solved through community-based
      approaches.

PMID- 18627695
TI  - Effects of basic fibroblast growth factors on hypertrophic scarring in a rabbit
      ear model.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) was clinically proven to
      accelerate acute and chronic wound healing. Accelerated wound healing may lead to
      improved scarring. These studies suggested a possible antiscarring effect of bFGF
      during wound healing. Little was known about the precise pathologic mechanisms of
      bFGF on scarring formation. AIMS: The aim of this study was to investigate the
      effect of bFGF on hypertrophic scarring in a rabbit ear model and clarify the
      mechanism of bFGF on scar treatment. METHODS: The rabbit model of hypertrophic
      scarring was created and received of a low- or high-dose topical treatment three
      times daily for 1, 2, or 3 months. Then we examined the changes in the
      macroscopic and histopathologic characteristics of the scars. The expression of
      collagen, alpha(1)beta(2) integrin, and matrix metalloproteinase 1 (MMP-1) was
      studied by applying reverse transcriptase-polymerase chain reaction, enzyme
      linked immunosorbent assay, and Western blotting. RESULT: High-dose bFGF
      remarkably alleviated the scar in the rabbit ear model and decreased collagen
      type I expression. Further study revealed that bFGF remarkably enhanced MMP-1 and
      decreased alpha(1)beta(2) integrin expression. CONCLUSION: This study supports
      the hypothesis that bFGF exerted a net negative effect on collagen remodeling,
      therefore suggesting a potential antiscarring role.

PMID- 18627696
TI  - Diagnosis and follow-up of keratoacanthoma-like lesions: clinical-histologic
      study of 43 cases.
AB  - BACKGROUND: Keratoacanthoma (KA) is easily confused with squamous cell carcinoma
      (SCC) on a clinical or a histopathologic basis. However, KA undergoes spontaneous
      regression, whereas SCC does not. OBJECTIVE: Our objective was to study the
      histopathologic features associated with clinical regression in KA-like lesions
      to support the therapeutic option. METHODS: Forty-three biopsies of KA-like
      lesions were taken at patient admission. One month later, surgical excision was
      performed in 18 growing lesions. Regressing lesions were left untreated. Classic
      histopathologic features and diagnosis were blindly recorded in both biopsies and
      surgical specimens. RESULTS: On a clinical and a histologic basis, 32 lesions
      were assessed as KA and 11 as SCC. Features that indicated malignancy were
      observed in both groups, but the probability of SCC was 31 times higher in tumors
      with five or more of such features. Several of the histologically atypical
      lesions were found to regress. CONCLUSION: SCCs and KAs have more pathologic
      similarities than differences, especially in the proliferative phase. The
      combination of the most useful features did not allow the nosologic diagnosis in
      difficult cases but helped. Differential diagnosis was easier to determine after
      the 1-month follow up. Complete surgical excision should be indicated in
      nonregressing and growing lesions.

PMID- 18627697
TI  - Treatment of vitiligo with narrow-band ultraviolet B: advantages and
      disadvantages.
AB  - BACKGROUND: Narrow-band ultraviolet B (NB-UVB) therapy for vitiligo is
      increasingly used in patients who are unresponsive to other forms of therapy.
      OBJECTIVE: This study measures levels of patient and physician satisfaction and
      the associated advantages and disadvantages of NB-UVB. METHODS: A retrospective
      chart review was conducted of the first 50 patients with vitiligo treated at the
      Photoderm Clinic in Ottawa, Ontario. Data were obtained from digital photographs
      and patient charts (n = 50). RESULTS: Percent repigmentation of the face and body
      was very good compared with the hands and feet (poor = 0-or< 33%; good = 33-or<
      66%; very good = >or= 66%). The physician and patients were satisfied with
      results achieved with NB-UVB therapy (very good [VG]: medical doctor [MD] 49%
      [95% CI 35-63], patient [Pt] 51% [95% CI 37-65]; good [G]: MD 24% [95% CI 12-36],
      Pt 22% [95% CI 10-34]). CONCLUSION: NB-UVB therapy is an effective treatment for
      vitiligo (ie, VG, repigmentation >or= 66%) that leads to high levels of patient
      and physician treatment-related satisfaction. Although there are disadvantages to
      NB-UVB therapy, the advantages outweigh the drawbacks. An objective evaluation
      such as the Vitiligo Area Scoring Index (VASI) is necessary to validate these
      findings. Additional limitations include those inherent in retrospective study
      design.

PMID- 18627698
TI  - Angioma serpiginosum with linear distribution: case report and review of the
      literature.
AB  - BACKGROUND: Angioma serpiginosum is a vascular anomaly that classically presents
      in childhood and predominantly affects females. OBJECTIVE: To present a case of a
      young woman with linear distribution of angioma serpiginosum and review the
      common clinical characteristics and presentation of this condition. METHODS: Case
      report with skin biopsies and dermoscopic findings. RESULTS: A clinical
      examination revealed numerous irregular punctate red macules in a linear
      distribution over the right arm. On dermoscopy, the lesions appeared as multiple
      sharply demarcated red lagoons. The histopathologic findings of dilated blood
      vessels in the papillary dermis with absence of other changes confirmed the
      diagnosis of angioma serpiginosum. CONCLUSION: Angioma serpiginosum is a rare
      entity that can be distinguished by clinical and histopathologic examinations.
      Lack of recognition of this condition may lead to unnecessary investigations and
      delayed treatment.

PMID- 18627699
TI  - Long-term management of generalized pustular psoriasis with infliximab: case
      series.
AB  - BACKGROUND: Infliximab, a tumor necrosis factor alpha antagonist, has recently
      been shown to be successful for the short-term treatment of generalized pustular
      psoriasis (GPP) in multiple case reports. OBJECTIVE: The goal of this case series
      was to assess the efficacy of the longer-term management of GPP with infliximab.
      METHODS: Three patients with severe GPP were followed to assess the efficacy of
      long-term treatment with infliximab. RESULTS: Infliximab therapy was more
      efficacious with infusion every 6 to 8 weeks in combination with methotrexate.
      CONCLUSION: Infliximab may be efficacious for some patients for the long-term
      management of GPP. Maintaining a strict infliximab infusion schedule and
      concomitant methotrexate therapy may decrease infusion reactions and increase
      efficacy.

PMID- 18627700
TI  - Improvement in both Raynaud disease and hyperhidrosis in response to botulinum
      toxin type A treatment.
AB  - BACKGROUND: A patient with concurrent Raynaud disease presented for hyperhidrosis
      of the axillae and palms. After a positive response to botulinum toxin type A
      (BoNTA) for axillary hyperhidrosis, she returned requesting palmar treatment.
      OBJECTIVES: Our goal was to investigate the effect of BoNTA on Raynaud disease in
      concurrent hyperhidrosis with respect to color change, swelling, and digital
      pain. METHODS: The patient had treatment with 100 units of BoNTA to one hand at
      first, with the other being a negative control, followed by treatment of the
      second hand 1 week later. RESULTS: After the injection into the first palm, the
      patient demonstrated an 85% reduction in palmar hyperhidrosis and a significant
      improvement in her Raynaud symptoms. Specifically, the BoNTA-treated hand had
      reduced swelling, color change, and pain, whereas the untreated control hand
      remained affected. After the second hand was treated, it, too, demonstrated the
      same positive results. CONCLUSIONS: Our case report of concurrent Raynaud disease
      and palmar hyperhidrosis shows significant improvement in both conditions to
      BoNTA administration. The physiology is multifactorial and relates to BoNTA's
      effect on acetylcholine, noradrenaline, substance P, calcitonin gene-related
      peptide, and glutamate release from nerve terminals. These results present an
      encouraging novel treatment option in dermatology for patients with Raynaud
      disease.

PMID- 18627701
TI  - Melanonychia following mohs surgery for recurrent squamous cell carcinoma in situ
      of the nail bed.
AB  - BACKGROUND: Longitudinal melanonychia (LM) is characterized by the appearance of
      a longitudinal pigmented band in the nail plate. Melanonychia can occur from many
      causes, including racial predisposition, trauma, drugs, pregnancy, Addison
      disease, Peutz-Jeghers syndrome, Laugier-Hunziker syndrome, Bowen disease,
      onychomycosis, benign nail matrix nevi, and melanoma. OBJECTIVE: We present a
      case of diffuse melanonychia developing several months following Mohs surgery for
      a human papillomavirus-induced recurrent squamous cell carcinoma in situ of the
      nail bed. CONCLUSIONS: This case illustrates the diagnostic dilemma in
      determining the etiology of the melanonychia and considers the differential
      diagnosis.

PMID- 18627702
TI  - Asymptomatic palmar pits: clinical evaluation of six cases and review of the
      literature.
AB  - BACKGROUND: Palmar pits are intriguing and are found in association with diverse
      dermatologic conditions. Some are innocuous, whereas others have sinister
      implications. OBJECTIVE: Six cases of asymptomatic palmar pits are described, and
      the literature is reviewed in brief. METHOD AND RESULTS: Of the six patients,
      five were male and one was female, with a mean age of 63.5 years. In all six
      patients, the palmar pits were noticed incidentally during a cutaneous
      examination for some other unrelated dermatoses, except in one in whom the pits
      were the reason for visiting a dermatologist. The number of pits varied from one
      to nine. Dupuytren contracture was observed in five patients. Sole involvement
      was seen in only one patient. None had overlying hyperkeratosis or associated
      symptoms relating to palmar pits. CONCLUSIONS: Palmar pits may have sinister
      implications in conditions such as nevoid basal cell carcinoma syndrome or Cowden
      syndrome. The association of palmar pits and Dupuytren contracture seems to be
      common but is underreported. Palmar pits may be the clinical cutaneous sign of
      systemic diseases and may sometimes provide a diagnostic clue to other
      dermatoses. This report emphasizes the significance of the art of clinical
      observation in dermatology.

PMID- 18627703
TI  - A review of hormonal therapy for female pattern (androgenic) alopecia.
AB  - Female pattern hair loss (female androgenetic alopecia) is a common, but
      puzzling, condition in women. Approximately 10 percent of pre-menopausal women
      show evidence of androgenetic alopecia. Age increases the incidence and 50-75
      percent of women 65 years or older suffer from this condition. Only 2 percent
      topical mindoxidil is approved for treating female androgenetic alopecia. Reviews
      suggest that anti-hormonal therapy (e.g. cyproterone acetate, spironolactone) is
      helpful in treating female pattern alopecia in some women who have normal hormone
      levels. The use of hormonal therapies is most extensively studied in post
      menopausal women. Several studies have suggested that cyproterone acetate with or
      without ethinyl estradiol and spironolactone can ameliorate female androgenetic
      alopecia in women with normal hormone levels, but larger controlled studies need
      to be done. Flutamide was found to be more effective than spironolactone or
      cyproterone in one study. Testosterone conversion inhibitors have been tried in
      post-menopausual women with normal hormone levels to treat alopecia. No study has
      shown that 1 mg of finasteride effectively treats female androgenetic alopecia
      but doses of 2.5 and 5 mg finasteride have helped some women in a few open
      studies. One case report notes the utility of dutasteride after finasteride
      failed. The role and place of anti-androgentic agents in female androgenetic
      alopecia in both pre and post-menopausal women remains to be fully defined. The
      need for effective agents is highlighted by the paucity of effective treatments
      and the substantial psychosocial impact of alopecia on women.

PMID- 18627704
TI  - Recessive dystrophic epidermolysis bullosa: presentation of two forms.
AB  - Dystrophic epidermolysis bullosa (DEB) and aplasia cutis congenita (ACC), also
      known as congenital localized absence of skin (CLAS) are rare clinical entities.
      Aplasia cutis congenita presented in conjunction with simplex, junctional, or
      dystrophic types of epidermolysis bullosa (EB) is classified as type-6 ACC. This
      association was initially described and referred in the literature as Bart
      syndrome. We describe two cases of recessive DEB (RDEB), one with the major
      Hallopeau-Siemens (RDEB-HS) subtype and one case with the minor RDEB inversa
      (RDEB-I) subtype associated with ACC localized on the lower extremities. Full
      clinical history and transmission electron microscopic findings are presented for
      both cases. To date, only five cases of RDEB presenting with ACC have been
      reported in the literature. Detailed descriptions of the association of RDEB and
      ACC in the literature are scarce. It seems that this condition is probably more
      common in clinical practice than described in the literature. Our findings
      confirm that the term, Bart syndrome, should not be considered as a separate
      entity or clinical variant of dominant dystrophic EB as it was initially
      described. Congenital localized absence of skin may be associated with any of the
      three major types of EB (simplex, junctional, or dystrophic).

PMID- 18627705
TI  - Langerhans cell histiocytosis: a case report and summary of the current
      recommendations of the Histiocyte Society.
AB  - Langerhans cell histiocytosis (LCH) is a rare proliferative disorder in which
      pathological Langerhans cells (LCs) accumulate in a variety of organs.
      Historically, the nomenclature regarding LCH has been confusing because the
      disease had been sub-categorized simply based upon different clinical
      manifestations. Herein, we report a child with the classic finding of
      disseminated LCH and summarize the current recommendation of the Histiocyte
      Society regarding the classification, evaluation, prognosis and treatment of LCH.

PMID- 18627706
TI  - An unusual presentation of a common disease.
AB  - We present a case of perforating granuloma annulare (PGA), in which we show the
      natural history of lesions and outline the different clinical types. Our patient
      responded well to intralesional triamcinolone acetonide 10mg/ml injections.
      Although she was otherwise well, PGA can be associated with diabetes mellitus in
      up to 17 percent of cases. Differential clinico-histopathological diagnosis,
      specifically in relation to necrobiosis lipoidica diabeticorum is being
      discussed. Treatment for PGA is difficult; apart from topical and/or
      intralesional steroids (clearance up to 54% in one case series), other options
      include Psoralen plus UVA (PUVA), systemic isotretinoin, chloroquine or
      hydroxylchloroquine, sulphapyridine, dapsone, topical application of imidazole
      creams, and liquid nitrogen. Spontaneous remission has also been reported in up
      to 77 percent in one case series.

PMID- 18627707
TI  - Skin lesions in carpet hand-weavers.
AB  - Carpet hand-weaving is an important industry in Iran. The repetitive trauma to
      hands in this occupation produces typical nodules and plaques. The skin lesions
      from 150 carpet weavers are reported. The characteristic carpet nodule is
      clinically and histologically described.

PMID- 18627708
TI  - Vesicular pityriasis rosea: an atypical presentation.
AB  - Pityriasis rosea (PR) is an acute, self-limited papulosquamous dermatosis
      localized on the trunk and extremities. PR is seen most frequently in adolescents
      and young adults. Many atypical forms of the disease have been reported in the
      literature. We report a rare atypical type of PR with vesicles on the
      erythematous macules and plaques.

PMID- 18627709
TI  - Leopard syndrome.
AB  - The L.E.O.P.A.R.D. syndrome is an autosomal, dominant disorder with
      characteristic features that include: multiple lentigines, cafe au lait spots,
      electrocardiographic conduction abnormalities, ocular hypertelorism, obstructive
      cardiomyopathy, pulmonary stenosis, abnormal (male) genitalia, retardation of
      growth, and deafness. Patients do not usually present all the clinical features
      traditionally associated with the disorder. Indeed, several features are not
      present until late in life and do not become clinically manifest until puberty.
      It has been observed that this syndrome is caused by a "missense" mutation in
      PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located on
      chromosome 12q22. A diagnosis of LEOPARD syndrome may be established exclusively
      on the basis of clinical criteria. In our case, the patient was diagnosed with
      the syndrome late in his life when he was already exhibiting all its distinctive
      clinical features. We have reported the case of a LEOPARD syndrome patient
      exhibiting extremely elongated vertebral and basilar arteries previously
      undescribed in the literature.

PMID- 18627710
TI  - Imiquimod for restoring local immunity in a renal transplant patient with
      persistent keratoacanthoma.
AB  - Keratoacanthoma (KA), a cutaneous neoplasm histologically resembling squamous
      cell carcinoma, is characterized by rapid growth and common spontaneous
      regression. The regression depends on an individual's immune response. We are
      reporting a case of a 53-year-old man who presented with an ulcerated tumor,
      which had arisen as a nodular lesion 9 months earlier. This was localized on the
      the left thumb. The patient had undergone a kidney transplant after severe
      glomerulonephritis. Following the operation, he was treated with systemic
      immunosuppressive drugs and developed multiple non-melanoma skin cancers. The
      histology examination of biopsy specimens was consistent with keratoacanthoma and
      showed low-density chronic inflammatory cells. Our patient refused surgical
      excision, so we prescribed imiquimod 5 percent cream once daily for 5 days a
      week. After 6 weeks of treatment the lesion had regressed completely, yielding an
      excellent cosmetic result. Continued resolution was documented 3 years after
      treatment. The patient had no signs of graft rejection related to the imiquimod
      treatment.

PMID- 18627711
TI  - [Classic dissemination of Kaposi's sarcoma: report of a case].
AB  - An 86-year-old male presented with a disseminated dermatosis characterized by
      erythematous and violaceous papules and nodules of 0.5-1.0 cm in diameter. The
      upper and lower limbs were affected and lower limb edema was promiment. Upon
      histological examination the diagnosis of classic Kaposi's Sarcoma was confirmed.
      There is still controversy if Kaposi's Sarcoma is a true neoplasm, a
      proliferative reaction, or both.

PMID- 18627712
TI  - Confluent and reticulate papillomatosis.
AB  - A 24-year-old man had an asymptomatic rash on his chest and arms for one year. On
      his chest, there were brown confluent plaques in a reticulate pattern. A scraping
      for fungus was negative. A biopsy showed papillomatosis, orthokeratosis, and
      melanin pigment at the basal layer of the epidermis. The patient was started on a
      six-week course of minocycline twice/day. Six weeks later, the patient was
      completely clear of the rash. Confluent and reticulate papillomatosis is an
      uncommon dermatosis that tends to occur on the chest. The pathogenesis is
      unknown. Minocycline has been reported to work well in the treatment of this
      dermatosis.

PMID- 18627713
TI  - Tuberculous empyema necessitatis. A rare cause of cutaneous abscess in the XXI
      century.
AB  - A 24-year-old Moroccan man was admitted to the hospital because of a tumor of the
      abdominal wall, fever, and purulent sputum. Imaging tests showed the presence of
      a pleural effusion and tumor in the right abdominal wall. The organized
      collection of liquid in the mass was contiguous with the thoracic collection and
      that of the subphrenic space. Thoracocentesis removed purulent material
      suggestive of empyema. Cultures and polymerase chain reaction (PCR) tests
      confirmed the diagnosis of tuberculous empyema. Empyema necessitatis refers to
      empyema that extends into the extrapleural space through a defect in the pleural
      surface. Various infectious etiologies may be responsible. Tuberculous empyema
      necessitatis is a rare complication of tuberculosis (TB); our case is even more
      unusual because this condition presented as an abdominal wall abcess and the
      patient was immunocompetent. His only predisposing factors were his country of
      origin, where there is a high prevalence of TB and the delay in diagnosis due to
      a lack of access to health care.

PMID- 18627714
TI  - The post-thrombotic syndrome - a condition to prevent.
AB  - The incidence of the post-thrombotic syndrome (PTS) is increasing along with the
      incidence of deep vein thrombosis (DVT). The overall frequency of PTS ranges from
      20 percent to 50 percent of DVT patients; severe PTS, which includes leg ulcers,
      occurs in a quarter of cases. Because of its severity and chronicity, PTS is
      associated with great morbidity and cost. Its diagnosis is primarily based on the
      presence of typical symptoms and signs, but objective evidence of venous valvular
      reflux can help to confirm the diagnosis. Because therapeutic options for PTS are
      extremely limited and results are often disappointing, prevention, recognition of
      clinical signs or complications, and early treatment remain the keys to reducing
      its morbidity. The prevention of DVT recurrence by anticoagulation and use of
      graduated compression stockings is likely to reduce the risk of PTS. There is no
      proven role for thrombolysis in preventing PTS.

PMID- 18627715
TI  - Pruritic bluish-black subcutaneous papules on the chest.
AB  - Steatocystoma multiplex (SM) is characterized by multiple dermal cysts involving
      the pilosebaceous glands. Although most presenting cases are sporadic, there is a
      rare familial syndrome involving a mutation in keratin 17 (K17) that is inherited
      in an autosomal dominant fashion. SM often presents concomitantly with eruptive
      vellus hair cysts (EHVS) and pachyonychia congenital type 2 (PC-2). We report a
      sporadic case of SM in a 21-year-old man.

PMID- 18627716
TI  - Rowell syndrome - case report and review of the literature.
AB  - Rowell syndrome is a rare distinctive entity first described in 1963 by Rowell
      and coworkers. It consists in erythema multiforme-like lesions associated with
      lupus erythematosus. Zeitouni et al. recently redefined the major and minor
      diagnostic criteria. Major criteria are lupus erythematosus, erythema multiforme
      like lesions and speckled pattern of antinuclear antibody. Minor criteria are
      chilblains, positive anti-La (SS-B) or anti-Ro (SS-A) antibody and reactive
      rheumatoid factor. We report a case of a 63-year-old woman, with no previous
      history of lupus erythematosus, who developed erythema multiforme-like lesions
      and laboratory findings consistent with Rowell syndrome.

PMID- 18627717
TI  - Localized and persistent erythema nodosum leprosum - a rare variant?
AB  - Erythema nodosum leprosum (ENL) or Type-2 Lepra reaction is a manifestation of
      type III hypersensitivity response and usually occurs in certain cases of
      lepromatous and borderline lepromatous leprosy. It is usually generalized and
      evanescent, and responds well to oral corticosteroid therapy. Here we report an
      unusual case of persistent and localized ENL in a 19-year-old girl, which could
      be diagnosed with the aid of skin biopsy and histopathological examination.

PMID- 18627718
TI  - Longitudinal leukonychia in Hailey-Hailey Disease: a sign not to be missed.
AB  - A 54-year-old male presented with a painful, erythematous, fissured plaque
      involving the left groin and adjacent scrotal skin. In addition, he exhibited
      white longitudinal bands and ridges on his fingernails, more prominent on thumb
      nails. Skin biopsy from the left groin confirmed the diagnosis of chronic
      familial benign pemphigus (Hailey-Hailey disease). To the best of our knowledge,
      this is the first case report from India in which we have described nail
      involvement in Hailey-Hailey disease.

PMID- 18627719
TI  - Friction induced skin tags.
AB  - Skin tags are common benign neoplasm located predominantly in intertriginous
      skin. Generally of cosmetic concern, they can be easily treated with cryotherapy,
      electrodessication or snip-excision. Despite their high incidence data about
      their etiopathogenesis are scarce in the medical literature. We describe a
      patient who developed multiple skin tags arranged in a linear fashion suggesting
      an etiopathogenic role for friction.

PMID- 18627720
TI  - Silver sulfadiazine therapy in widespread bullous disorders: potential for
      toxicity.
AB  - Silver sulfadiazine (SSD) cream, most known for its use in the treatment of
      extensive burn wounds, is commonly used in the management of erosions in bullous
      disorders. The beneficial antibacterial effect of SSD use is not without risk, as
      silver toxicity has been well documented in burn patients. Renal insufficiency
      accelerates silver accumulation and thus toxicity. Data on silver toxicity in
      patients with primary blistering disorders is scarce; however the literature
      regarding silver toxicity in burn patients may be applicable to patients with
      bullous diseases. Hence we recommend that clinicians exercise caution when
      prescribing protracted wound care with SSD for blistering disorders.

PMID- 18627721
TI  - Nodular fibrosis: a rare complication of non filarial lymph edema.
AB  - Lymphedema is a soft-tissue swelling that occurs following lymphatic fluid
      accumulation. Edema is due to insufficient lymphatic drainage that occurs because
      of lymphatic vessel obstruction or absence [1]. Chronic lymphedema can cause a
      clinical picture of tense non-pitting edema with thickened epidermis that is due
      to accumulation of protein and lipids in the connective tissue. In the early
      stages pitting edema is seen, but with progression of disease, fibrosis occurs
      and then edema becomes tense. Hyperplasic changes with warty epidermis and then
      elephantiasis become evident. The disability due to limb swelling can be severe
      but the overall prognosis is good [1]. Nodular fibrosis is an uncommon
      complication of elephantiasis [2].

PMID- 18627722
TI  - Evaluation of serum iron and ferritin levels in alopecia areata.
AB  - Although immunologic processes and hereditary factors are suggested to play an
      important role in alopecia areata, the specific etiology is unclear. Iron
      deficiency has been suggested to play a role, but its effect is controversial. In
      our case control study, we found a higher mean level of serum iron and ferritin
      and a lower mean level of TIBC in patients compared to control subjects, but the
      differences did not reach significance.

PMID- 18627723
TI  - Ode to the case report.
AB  - Although many medical journals routinely shun publication of case reports, these
      communications still can play a major educational role. Unexpected presentations,
      heretofore unreported adverse events and new associations may be illuminated.
      Although not as rigorous as placebo-controlled, double-blind studies, case
      reports do have a high degree of sensitivity for detecting novelty. Thus, they
      may also serve a useful purpose in directing future investigation.

PMID- 18627724
TI  - Common misconceptions in contact dermatitis counseling.
AB  - Both physicians and patients hold many misconceptions when it comes to allergen
      avoidance. Ten commonly held misconceptions are exposed, allowing more accurate
      approach to the individual with cutaneous allergies.

PMID- 18627725
TI  - Erythema nodosum associated with infliximab therapy.
AB  - A number of unrelated cutaneous adverse events have been rarely associated with
      administration of infliximab. This drug has been used to control erythema nodosum
      when the latter was associated with Crohn disease. We herein report the
      paradoxical occurrence of erythema nodosum, verified by repeated challenges,
      following infliximab infusion given for ankylosing spondylitis. Despite this side
      effect, the patient elected to continue therapy due to a high degree of efficacy.

PMID- 18627726
TI  - Vasodilatory adverse events associated with topical imiquimod 5 percent cream.
AB  - The immune response modulator, imiquimod, has a wide ranging utility in
      dermatology. Some rare adverse events are easily explained based upon its
      mechanism of action (such as induction of vitiligo and worsening of psoriasis).
      We report the occurrence of cutaneous vasodilatory side effects, angioedema and
      urticaria, which accompanied the treatment of basal cell carcinomas in two
      patients. These phenomena must be quite rare considering a paucity of similar
      reports in the literature.

PMID- 18627727
TI  - Actinomycetoma with negative culture: a therapeutic challenge.
AB  - Nocardia, Actinomyces, and Streptomyces species comprise the three broad classes
      of organisms that are causative for bacterial mycetoma. Although culture and
      molecular laboratory studies can usually identify the precise etiologic agent in
      bacterial mycetoma, occasionally these methods fail to clarify this situation. We
      report a classic clinical case of this infectious disease where usual diagnostic
      methods failed to identify the responsible organism, and discuss the empiric
      approach to such cases.

PMID- 18627728
TI  - Herpes vegetans as a sign of HIV infection.
AB  - Herpes progenitalis can present in bizarre ways when seen in conjunction with
      altered immune status. In the recent past, a small number of individuals have
      been described with herpes vegetans, an exophytic, proliferative lesion that
      resembles either a verrucous or malignant growth. This phenomenon can occur on
      the digits, genitalia or perioral skin. We present a case of a vegetating penile
      plaque attributed to herpesvirus in an HIV-positive patient.

PMID- 18627729
TI  - Phthiriasis palpebrarum: a common culprit with uncommon presentation.
AB  - Since infestation of the eyelashes by pubic lice is relatively uncommon, it might
      well be misdiagnosed as bacterial conjunctivitis, allergic contact dermatitis, or
      seborrheic and rosacea blepharitis. We present and graphically illustrate a case
      of blepharoconjunctivits attributed to P. Pubis infestation and offer further
      support for the use of the ophthalmologic agent 4 percent pilocarpine gel as a
      primary or adjunctive treatment modality.

PMID- 18627730
TI  - Tinea corporis masquerading as subacute cutaneous lupus erythematosus.
AB  - Few papers discuss the potential challenge of differentiating dermatophytosis
      from subacute cutaneous lupus erythematosus. This masquerade, most often manifest
      on the face, is of both clinical and therapeutic importance. We report a patient
      whose extensive tinea corporis very closely mimicked SCLE. The threshold for
      biopsy should be low in cases that exhibit atypical features for either of these
      entities.

PMID- 18627731
TI  - Argyria attributed to silvadene application in a patient with dystrophic
      epidermolysis bullosa.
AB  - Argyria is most commonly reported in association with prolonged ingestion of
      silver-containing medicaments. This case illustrates the rather unique case of
      development of argyria following application of silver sulfadiazine in a patient
      with epidermolysis bullosa.

PMID- 18627732
TI  - Lichen nitidus actinicus: a distinct facial presentation in 3 pre-pubertal
      African-American girls.
AB  - Lichen nitidus is a relatively common inflammatory disorder of uncertain etiology
      seen primarily in the pediatric population. A rare variant may demonstrate a
      photodistribution of characteristic lesions. We describe 3 cases of lichen
      nitidus actinicus with prominent facial lesions.

PMID- 18627733
TI  - Rapidly involuting congenital hemangioma: case report and review of the
      literature.
AB  - Various forms of angiomata may be encountered in the neonate and infant. Both
      histology and histochemistry, along with history and morphology, may help
      establish the correct diagnosis. We report a case of rapidly involuting
      congenital hemangioma and summarize the features characteristic of this vascular
      neoplasm.

PMID- 18627734
TI  - Surgical pearl: the temporary assistant.
AB  - A simple maneuver is presented which simultaneously facilitates both adequate
      surgical site exposure and sufficient traction. A single suture with high tensile
      strength can be utilized to this end. This technique is especially helpful when
      the cutaneous surgeon is operating alone.

PMID- 18627735
TI  - Axillary syringomas.
AB  - Syringomas are common benign neoplasms encountered mostly around the eyes.
      However, as described herein, these tumors can occur in atypical locations such
      as the axilla. The differential diagnosis revolves around those entities more
      likely seen in this anatomical location (such as Fox-Fordyce, Hailey-Hailey and
      Darier diseases). Various ablative modalities are curative.

PMID- 18627736
TI  - Familial basaloid follicular hamartoma: a report of one family.
AB  - Basaloid follicular hamartoma is a rare but benign adnexal neoplasm that can
      simulate basal cell carcinoma. Both sporadic and familial variants have been
      described. We illustrate a family cluster of this unusual entity which presented
      as milia-like or hyperpigmented papules. Criteria for distinction between the
      hamartoma and carcinoma are delineated, although evolution of basaloid follicular
      hamartoma into basal cell carcinoma may also be a possibility.

PMID- 18627737
TI  - Sarcoidosis with subcutaneous lesions.
AB  - A 30-year-old man presented for evaluation of multiple, hypopigmented macules and
      erythematous papules on his upper and lower lips and upper extremities. He
      subsequently developed firm, non-tender, subcutaneous, mobile nodules on the left
      forearm, left calf, and right thigh. Clinical and histopathologic features were
      consistent with cutaneous and subcutaneous sarcoidosis. Systemic evaluation
      showed no evidence of extracutaneous involvement. Subcutaneous sarcoidosis is a
      rare form of nodular cutaneous sarcoidosis. Typical skin findings are painless,
      firm, mobile nodules without overlying epidermal involvement and with a
      predilection for the trunk and extremities. Histopathologic alterations include
      epilthelioid cell tubercles in the subcutaneous fat. As this is a diagnosis of
      exclusion, other etiologies of granulomatous inflammation must be ruled out with
      tests and special stains. The mainstay of treatment is with oral glucocorticoids.

PMID- 18627738
TI  - Epidermodysplasia verruciformis.
AB  - A 29-year-old woman presented for evaluation of an ulcerated nodule on her right
      temple in the presence of numerous additional scaly papules, plaques, and
      seborrheic keratosis-like lesions that were distributed on her forehead, frontal
      scalp, and temples. Further examination showed pityriasis rosea-like lesions on
      her neck, back, and arms and verruca plana-like lesions on the dorsa of the hands
      and forearms. A biopsy specimen of the ulcerated nodule showed a nodular basal
      cell carcinoma. Two additional biopsy specimens from her forehead showed one
      invasive and one in-situ squamous-cell carcinoma. Both biopsy specimens
      demonstrated histopathologic evidence of epidermodysplasia verruciformis.

PMID- 18627739
TI  - Hereditary papulotranslucent acrokeratoderma.
AB  - A 79-year-old woman presented with a history of peeling of the palms and soles
      that began in young adulthood, with exacerbation after exposure to water. Her
      mother, 2 sisters, and a female maternal cousin have similar symptoms. Physical
      examination showed scale and hyperlinearity of the palms. Brief exposure to water
      initiated the development of 1-to 2-mm, translucent, white papules that were
      distributed diffusely on the palmar surface, with a concentration at the palmar
      margins and pressure points. Histopathologic examination showed an acanthotic
      epidermis with a central depression that was filled with compact orthokeratosis.
      The physical examination and histopathologic findings are consistent with a
      diagnosis of hereditary papulotranslucent acrokeratoderma.

PMID- 18627740
TI  - X-Linked ocular albinism; Nettleship-Falls ocular albinism.
AB  - A 39-year-old man with foveal hypoplasia, nystagmus, and decreased visual acuity
      was found to have multiple, cutaneous, hypopigmented macules. Macromelanosomes
      were demonstrated in normal skin on histopathologic examination. The patient's
      constellation of findings along with a strong X-linked inheritance pattern in
      family members led to the diagnosis of X-linked ocular albinism, which is an
      uncommon condition that is characterized by congenital nystagmus, iris
      translucency, hypopigmentation of the ocular fundus, strabismus, foveal
      hypoplasia, photophobia, and impaired vision.

PMID- 18627741
TI  - Systemic lupus erythematosus with generalized chronic cutaneous (discoid) lupus
      erythematosus.
AB  - A 24-year-old pregnant African-American woman had a 3-4 year history of chronic,
      scarring, hyperpigmented plaques on her scalp, face, trunk, and extremities. She
      complained of joint pain and fatigue. Clinical presentation, laboratory data, and
      histopathologic features were consistent with systemic lupus erythematosus in a
      patient with generalized chronic discoid lupus erythematosus. This subtype is a
      distinct lupus erythematosus subset that rarely develops renal disease and has a
      relatively benign but chronic course.

PMID- 18627742
TI  - Mosaic neurofibromatosis type 1.
AB  - A 24-year-old man presented with numerous lentigines and multiple cafe-au-lait
      macules on both sides of the face, neck, and trunk as well as on the proximal
      area of the upper extremities and in the axillae. The pigmented lesions had a
      Blaschko-linear distribution on the upper trunk and were limited to the left side
      of the abdomen, with a sharp demarcation at the midline. Multiple, cutaneous
      neurofibromas were found on the trunk, and ophthalmologic examination showed a
      Lisch nodule in the left iris. The clinical findings and their widespread but
      segmental distribution were consistent with a diagnosis of mosaic
      neurofibromatosis type 1.

PMID- 18627743
TI  - Noninvoluting congenital hemangioma.
AB  - An 8-year-old boy presented with a lifelong history of a vascular mass overlying
      his right mandible with central coarse telangiectasias and peripheral pallor.
      Histopathologic examination showed a proliferation of blood vessels in the
      dermis. Ultrasound examination identified a mix of high- and low-flow vessels
      within the lesion. These findings were consistent with a noninvoluting congenital
      hemangioma, a rare vascular tumor that is fully formed at birth that subsequently
      grows proportionately with the patient and does not regress.

PMID- 18627744
TI  - Cutaneous Rosai-Dorfman disease.
AB  - A 63-year-old woman developed multiple nodules at the site of a recently biopsied
      proliferation of CD 68+ histiocytes. Clinical lymphadenopathy was not present on
      physical examinaton or on computed tomography scans. A subsequent skin biopsy
      specimen showed changes consistent with Rosai-Dorfman disease. Rosai-Dorfman
      disease is a benign, histiocytic proliferative disorder also known as sinus
      histiocytosis with massive lymphadenopthy. A particularly rare, extranodal,
      purely cutaneous form has been described. Spontaneous regression tends to occur
      over months to years, with surgical intervention remaining the most effective
      treatment. Documented success with a number of other therapies has been reported,
      which include systemic high-dose thalidomide in extensive cutaneous disease.

PMID- 18627745
TI  - Generalized essential telangiectasia.
AB  - A 56-year-old woman presented with multiple, erythematous cutaneous vessels that
      blanched with diascopy and were symmetrically distributed over both lower and
      upper extremities. The lesions had been present for approximately 6 years and
      were asymptomatic. Generalized essential telangiectasia (GET) is an idiopathic
      syndrome of widespread, asymptomatic telangiectases of unknown cause. In our
      patient, an extensive laboratory evaluation showed low levels of circulating
      vitamin C as well as the presence of urinary matrix metalloproteinases. The
      relevance of these abnormal findings is unclear. No uniformly effective treatment
      exists for GET. Our patient was started on oral doxycycline and was referred for
      laser therapy.

PMID- 18627746
TI  - Eruptive xanthomas.
AB  - A 26-year-old woman presented for evaluation of multiple, red-yellow papules that
      had been appearing over the course of 2 months on the extensor surfaces of the
      upper extremities, dorsal aspects of the hands, thighs, and buttocks. Serum lipid
      evaluation showed hypertriglyceridemia in a patient with a recent history of
      pancreatitis. A diagnosis of eruptive xanthomas was made based on clinical,
      laboratory, and histopathologic findings.

PMID- 18627747
TI  - Nephrogenic fibrosing dermopathy.
AB  - A 75-year-old woman with end-stage renal disease on hemodialysis presented with a
      2-month history of progressive skin thickening of the lower extremities. A punch
      biopsy specimen showed plump fibroblasts entrapping collagen bundles and positive
      staining for CD34 and procollagen. These changes were consistent with a diagnosis
      of nephrogenic fibrosing dermopathy (NFD). Nephrogenic fibrosing dermopathy is a
      rare, sclerosing disorder in patients with renal failure, which may be mistaken
      for scleromyxedema. The etiology of NFD is unclear but may be associated with
      systemic involvement, antecedent surgical procedures, gadolinium, or an
      underlying hypercoagulable state. The treatment is limited, and only a few
      reported cases have shown remission after stopping dialysis in transient renal
      failure.

PMID- 18627748
TI  - Multiple apocrine hidrocystomas.
AB  - A 83-year-old woman presented with a 7-year history of translucent papules that
      were scattered diffusely over her nose, peri-orbital region, and cheeks. These
      lesions were exacerbated by heat and exercise. Histopathologic examination of a
      biopsy specimen from the cheek showed a thin-walled cyst lined by a flattened bi
      layered epithelium that exhibited decapitation secretion in the upper part of the
      epidermis. A diagnosis of multiple apocrine hidrocystomas was made based on the
      clinical and histopathologic findings, and the patient is currently considering
      treatment options. These include electrodesiccation, excision, trichloracetic
      acid, carbon-dioxide laser, and 1450-nm diode laser.

PMID- 18627749
TI  - Erythrokeratoderma variabilis.
AB  - A 51-year-old woman presented with well-demarcated, erythematous patches and
      hyperkeratotic plaques that were arranged symmetrically on the upper extremities.
      Her skin lesions first appeared at age 17, and there was a family history of
      similar skin lesions in nine of her eleven siblings. Physical and emotional
      stress increased the number and intensity of her skin lesions as did chocolate.
      The distribution of lesions on her skin had changed over time; however, the
      lesions consistently appeared symmetrically and favored the extensor surfaces of
      her extremities. The physical examination, histopathologic findings, and family
      history were consistent with a diagnosis of erythrokeratoderma variabilis (EKV),
      a rare genodermatosis caused by various mutations in connexin genes. Connexin
      genes code for proteins that form intercellular channels called gap junctions
      that allow for transport and signaling between neighboring cells in the
      epidermis. Mutations in connexin-31 and connexin-30.3 are known to cause the EKV
      phenotype, which presents as erythematous patches and hyperkeratotic plaques.
      Studies to examine the effectiveness of treatment of EKV have not been performed;
      however, several case reports suggest the efficacy of oral retinoids. After 4
      months of acitretin 25 mg per day, our patient experienced near complete
      clearance of her skin lesions.

PMID- 18627750
TI  - Papular mucinosis (discrete papular lichen myxedematosus).
AB  - A 56-year-old woman presented with small, skin-colored papules on the trunk and
      thighs. Histopathologic findings were consistent with papular mucinosis.
      Laboratory evaluation did not show an associated paraproteinemia. Treatment with
      topical glucocorticoids was unsuccessful. Papular mucinosis, also known as
      localized lichen myxedematosus, has been categorized into 4 subtypes. The
      discrete papular form, as seen in our patient, is characterized by a few to
      multiple, 2-5-mm, skin-colored, firm, waxy, dome-shaped papules on the trunk and
      proximal aspects of the extremities. By definition there is no associated
      paraproteinemia, but this form may be associated with human immunodeficiency
      virus infection. Focal or diffuse mucinous deposits are seen on histopathologic
      examination. The usual clinical course is slow cutaneous progression without
      spontaneous resolution. Treatment is empiric and is usually unsuccessful.

PMID- 18627751
TI  - Anaplastic large-cell T-cell lymphoma.
AB  - A 64-year-old woman presented with 2 years of pruritic and ulcerated nodules and
      tumors on the trunk and arms. Histopathologic examination showed a diffuse
      infiltrate that consisted of predominantly small lymphocytes and scattered large
      atypical multinucleated cells positive for CD30. These findings were consistent
      with a diagnosis of anaplastic large-cell T-cell lymphoma, which is a CD30+
      cutaneous lymphoma. This case highlights the importance of considering both
      histopathologic and clinical criteria in diagnosing a patient with a CD30+
      cutaneous lymphoma.

PMID- 18627752
TI  - White sponge nevus.
AB  - A 33-year-old-man presented with a 13-year history of asymptomatic, white,
      folded, soft, poorly-demarcated, diffuse plaques bilaterally on his buccal
      mucosae and lateral surfaces of his tongue. There is no family history of similar
      lesions. The physical examination and histopathologic findings were consistent
      with a diagnosis of white sponge nevus. This rare disorder is typically
      inherited; however, as in this case, there have been a few other cases reported
      without a familial background.

PMID- 18627753
TI  - Palisaded neutrophilic and granulomatous dermatosis.
AB  - A 22-year-old woman with mixed connective-tissue disease presented with a 5-month
      history of recurrent episodes of tender, erythematous papules, nodules, and
      edematous plaques on the upper extremities and thighs. Cutaneous lesions occurred
      in the setting of livedo reticularis. A biopsy specimen showed interstitial and
      perivascular inflammation with lymphocytes, macrophages, neutrophils, nuclear
      dust, collagen alteration, extravasated erythrocytes, and fibrin within small
      superficial blood vessels. These changes were consistent with a diagnosis of
      palisaded neutrophilic and granulomatous dermatosis, which is a rare entity that
      includes a combination of a neutrophilic infiltrate, abnormal or altered
      collagen, granuloma formation, and leukocytoclastic debris in the context of an
      immune-mediated collagen vascular or systemic disease. The underlying mechanism
      remains poorly understood. Treatment is limited, and resolution of lesions
      typically occurs within several months to years.

PMID- 18627754
TI  - Interstitial granulomatous dermatitis.
AB  - A 59-year-old woman with arthritis presented to the Skin Institute of New York
      with a 2-month history of asymptomatic, small, skin-colored papules that erupted
      symmetrically on the chest, back, and proximal extremities. Histopathologic
      examination of a biopsy specimen showed findings of interstitial granulomatous
      dermatitis. Clinical correlation suggested a diagnosis of interstitial
      granulomatous dermatitis with arthritis. No change in the lesions resulted from
      application of clobetasol 0.05 percent ointment to the affected areas.

PMID- 18627755
TI  - Amalgam tattoo.
AB  - A 53-year-old woman with a history of melanoma status-post excision two years
      prior presented with a 4-month history of 4, dark-brown macules on the inferior
      surface of her tongue. A biopsy specimen showed a squamous mucosa with chronic
      submucosal inflammation and brown pigment. The clinical and histopathologic
      findings were consistent with a diagnosis of amalgam tattoo. Amalgam tattoos are
      common, oral pigmented lesions that clinically present as isolated, blue, grey,
      or black macules on the gingivae, the buccal and alveolar mucosae, the palate,
      and/or the tongue. They are due to deposition of a mixture of silver, tin,
      mercury, copper, and zinc, which are components of an amalgam filling, into the
      oral soft tissues. Amalgam tattoos can either be treated surgically or with a Q
      switched ruby laser. In the case of our patient with the history of melanoma, her
      oral lesions proved not to be the more dire diagnosis of malignant melanoma.

PMID- 18627756
TI  - Oral lichen planus.
AB  - A 42-year-old woman presented with a 2-year history of persistent, gray-white lip
      discoloration and discomfort that had not improved after empiric treatment with
      topical 5-fluorouracil cream. Histopathologic examination demonstrated interface
      dermatitis with epidermal atrophy. A diagnosis of oral lichen planus was made
      based on clinicopathologic correlation, and treatment with topical tacrolimus
      ointment was initiated.

PMID- 18627757
TI  - Granuloma annulare, patch type.
AB  - A 64-year-old man was referred to the Bellevue Hospital Center Dermatology Clinic
      for evaluation of an asymptomatic eruption on his left inner arm, which had been
      present for 4 months and was unresponsive to topical anti-fungal therapy. One
      month after the initial eruption, 2 similar, asymptomatic lesions appeared on the
      right inner arm. The lesions were slowly expanding. A biopsy specimen from the
      left medial arm was consistent with interstitial granuloma annulare. The
      patient's clinical presentation was consistent with patch-type granuloma
      annulare. He was treated with a mid-potency topical glucocorticoid twice daily
      for 4 weeks without benefit. Since the eruption was asymptomatic, treatment was
      discontinued.

PMID- 18627758
TI  - Pseudolymphoma evolving into diffuse large B-cell lymphoma.
AB  - A 46-year-old man presented with a 1-year history of asymptomatic papules on the
      right arm, without an antecedent event. Initial clinical and histopathologic
      features were consistent with a pseudolymphoma without gene rearrangements, and
      the patient was treated with intralesional glucocorticoids. Four months later,
      the patient developed additional papules and plaques on the right arm, and, at
      this time, clinical and histopathologic features were most consistent with a T
      cell-rich, large B-cell lymphoma, with monoclonal immunoglobulin light chain gene
      rearrangement. Systemic evaluation showed no evidence of extracutaneous
      involvement. The transformation of a pseudolymphoma into a large B-cell lymphoma
      is a rare event. This patient's subtype, diffuse large B-cell lymphoma-other,
      carries an intermediate prognosis when compared to the more aggressive leg
      subtype and more indolent folliculocentric subtype. Potential therapeutic options
      include local radiotherapy, chemotherapy, and rituximab.

PMID- 18627759
TI  - Extragenital lichen sclerosus et atrophicus.
AB  - A 76-year-old woman with a history of eczematous dermatitis presented with a 9
      month history of a pruritic, eczematous eruption of the trunk. This eruption
      responded to topical glucocorticoids but recurred on discontinuation of treatment
      on multiple occasions. A biopsy specimen showed extragenital lichen sclerosus et
      atrophicus. The diagnosis of extragenital lichen sclerosus is reviewed with a
      comparison to classic lichen sclerosus in terms of clinical features,
      histopathologic characteristics, and treatment approaches.

PMID- 18627760
TI  - Alopecia universalis with twenty-nail dystrophy (trachyonychia).
AB  - A 43-year-old man presented with long-standing trachyonychia of all 20 nails,
      which worsened after the onset of alopecia universalis 18 months ago.
      Trachyonychia can be associated with alopecia universalis although the treatment
      strategies of both conditions differ. The principle of treating trachyonychia may
      involve regulating the differentiation of keratinocytes and/or reducing
      inflammation in the nail fold or nail matrix while treatment of alopecia
      universalis involves immunomodulation.

PMID- 18627761
TI  - Chronic actinic dermatitis.
AB  - A 71-year-old man presented with a six-year history of a pruritic, erythematous,
      blistering eruption of the face, chest, and arms. Clinical findings,
      histopathologic features, and phototests were consistent with a diagnosis of
      chronic actinic dermatitis. The patient also had contact allergy and photocontact
      allergy to multiple allergens. A discussion of chronic actinic dermatitis is
      presented.

PMID- 18627762
TI  - Striate palmoplantar keratoderma (Brunauer-Fohs-Siemens syndrome).
AB  - A 64-year-old man presented with focal hyperkeratotic plaques on the fingers,
      palms, and soles. Histopathologic and electron microscopic results were
      consistent with striate palmoplantar keratoderma. Treatment with topical
      keratolytics was unsuccessful. Striate palmoplantar keratoderma or Brunauer-Fohs
      Siemens syndrome is an autosomal dominant condition that presents with linear
      hyperkeratosis on the palms and fingers and focal plaques on the plantar aspects
      of the feet. Histopathologic features include hyperkeratosis, hypergranulosis,
      and acanthosis with no epidermolysis. Electron microscopic examination shows
      diminished desmosomes, clumped keratin filaments, and enlarged keratohyalin
      granules. The syndrome has been linked to mutations in desmoglein 1, desmoplakin,
      and keratin 1. Treatment may include keratolytics, oral retinoids, and surgical
      debridement.

PMID- 18627763
TI  - Lymphangioma circumscriptum.
AB  - A 54-year-old man presented for evaluation of multiple 1- to-4-mm, clear, pink,
      red, and black vesicles overlying hyperpigmented and erythematous indurated
      plaques on his right thigh and extending to his right inguinal fold. Clinical
      presentation and histopathologic features were consistent with lymphangioma
      circumscription. Lymphangioma circumscriptum is the most common cutaneous form of
      lymphangioma. Typical skin findings are multiple clear vesicles that may appear
      pink, red, or black. The first-line treatment option is surgical excision,
      although other modalities, such as laser therapy and sclerotherapy, have also
      been used successfully.

PMID- 18627764
TI  - Automated measurement of the static light scattering of macromolecular solutions
      over a broad range of concentrations.
AB  - A method and apparatus for automated measurement of the concentration dependence
      of static light scattering of protein solutions over a broad range of
      concentrations is described. The gradient of protein concentrations is created by
      successive dilutions of an initially concentrated solution contained within the
      scattering measurement cell, which is maintained at constant total volume. The
      method is validated by measurement of the concentration dependence of light
      scattering of bovine serum albumin, ovalbumin, and ovomucoid at concentrations up
      to 130 g/L. The experimentally obtained concentration dependence of scattering
      obtained from all three proteins is quantitatively consistent with the assumption
      that no significant self-association occurs over the measured range of
      concentrations.

PMID- 18627765
TI  - Constitutive Smad signaling and Smad-dependent collagen gene expression in mouse
      embryonic fibroblasts lacking peroxisome proliferator-activated receptor-gamma.
AB  - Transforming growth factor-beta (TGF-beta), a potent inducer of collagen
      synthesis, is implicated in pathological fibrosis. Peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor that
      regulates adipogenesis and numerous other biological processes. Here, we
      demonstrate that collagen gene expression was markedly elevated in mouse
      embryonic fibroblasts (MEFs) lacking PPAR-gamma compared to heterozygous control
      MEFs. Treatment with the PPAR-gamma ligand 15d-PGJ(2) failed to down-regulate
      collagen gene expression in PPAR-gamma null MEFs, whereas reconstitution of these
      cells with ectopic PPAR-gamma resulted in their normalization. Compared to
      control MEFs, PPAR-gamma null MEFs displayed elevated levels of the Type I TGF
      beta receptor (TbetaRI), and secreted more TGF-beta1 into the media. Furthermore,
      PPAR-gamma null MEFs showed constitutive phosphorylation of cellular Smad2 and
      Smad3, even in the absence of exogenous TGF-beta, which was abrogated by the ALK5
      inhibitor SB431542. Constitutive Smad2/3 phosphorylation in PPAR-gamma null MEFs
      was associated with Smad3 binding to its cognate DNA recognition sequences, and
      interaction with coactivator p300 previously implicated in TGF-beta responses.
      Taken together, these results indicate that loss of PPAR-gamma in MEFs is
      associated with upregulation of collagen synthesis, and activation of
      intracellular Smad signal transduction, due, at least in part, to autocrine TGF
      beta stimulation.

PMID- 18627766
TI  - TRIP12 functions as an E3 ubiquitin ligase of APP-BP1.
AB  - The NEDD8 pathway plays an essential role in various physiological processes,
      such as cell cycle progression and signal transduction. The conjugation of NEDD8
      to target proteins is initiated by the NEDD8-activating enzyme composed of APP
      BP1 and Uba3. In the present study, we show that APP-BP1 is degraded by ubiquitin
      dependent proteolysis. To study biological functions of TRIP12, a HECT domain
      containing E3 ubiquitin ligase, we used the yeast two-hybrid system and
      identified APP-BP1 as its binding partner. Immunoprecipitation analysis showed
      that TRIP12 specifically interacts with the APP-BP1 monomer but not with the APP
      BP1/Uba3 heterodimer. Overexpression of TRIP12 enhanced the degradation of APP
      BP1, whereas knockdown of TRIP12 stabilized it. In vitro ubiquitination assays
      revealed that TRIP12 functions as an E3 enzyme of APP-BP1 and additionally
      requires an E4 activity for polyubiquitination of APP-BP1. Moreover, neddylation
      of endogenous CUL1 was increased in TRIP12 knockdown cells, while complementation
      of the knockdown cells with TRIP12 lowered neddylated CUL1. Our data suggest that
      that TRIP12 promotes degradation of APP-BP1 by catalyzing its ubiquitination,
      which in turn modulates the neddylation pathway.

PMID- 18627767
TI  - Circadian regulation of response to oxidative stress in Drosophila melanogaster.
AB  - Circadian rhythms are fundamental biological phenomena generated by molecular
      genetic mechanisms known as circadian clocks. There is increasing evidence that
      circadian synchronization of physiological and cellular processes contribute to
      the wellness of organisms, curbing pathologies such as cancer and premature
      aging. Therefore, there is a need to understand how circadian clocks orchestrate
      interactions between the organism's internal processes and the environment. Here,
      we explore the nexus between the clock and oxidative stress susceptibility in
      Drosophila melanogaster. We exposed flies to acute oxidative stress induced by
      hydrogen peroxide (H(2)O(2)), and determined that mortality rates were dependent
      on time at which exposure occurred during the day/night cycle. The daily
      susceptibility rhythm was abolished in flies with a null mutation in the core
      clock gene period (per) abrogating clock function. Furthermore, lack of per
      increased susceptibility to H(2)O(2) compared to wild-type flies, coinciding with
      enhanced generation of mitochondrial H(2)O(2) and decreased catalase activity due
      to oxidative damage. Taken together, our data suggest that the circadian clock
      gene period is essential for maintaining a robust anti-oxidative defense.

PMID- 18627768
TI  - Pharmacogenetics of hormone replacement therapy for climacteric symptoms.
AB  - Hormone replacement therapy (HRT) is highly effective for women suffering from
      climacteric symptoms, with occasionally severe side effects. To determine which
      women needs HRT for climacteric symptoms indeed, pharmacogenetical approach for
      HRT was performed. Under the condition of minimal HRT, 33 patients required HRT
      for more than 1 year and the remaining 156 did not. Three single nucleotide
      polymorphisms (SNPs) in estrogen receptor alpha (ERalpha) gene and 3 SNPs and a
      microsatellite polymorphism in estrogen receptor beta (ERbeta) gene were analyzed
      using LightTyper and PCR. Homozygous for 18 CA repeats of D14S1026 (OR 8.00, 95%
      CI 2.56-25.02, P<0.001) and rs1256049 (OR 6.35, 95% CI 2.38-16.92, P=0.004) in
      ERbeta associated with minimal HRT. In contrast, rs1271572 in 789bp upstream
      region of ERbeta (OR 0.30, 95% CI 0.14-0.65, P=0.002) gene decreased HRT.
      rs2228480 in ERalpha gene also increased HRT. Tailored decisions can be expected
      on the future use of HRT referring genetic polymorphisms of individuals.

PMID- 18627769
TI  - Design and kinetic analysis of hammerhead ribozyme and DNAzyme that specifically
      cleave TEL-AML1 chimeric mRNA.
AB  - In order to develop the oligonucleotides to abolish an expression of TEL-AML1
      chimeric RNA, which is a genetic aberration that causes the acute lymphoblastic
      leukemia (ALL), hammerhead ribozymes and deoxyoligoribozymes that can
      specifically cleave TEL-AML1 fusion RNA were designed. Constructs of the
      deoxyribozyme with an asymmetric substrate binding arm (Dz26) and the hammerhead
      ribozyme with a 4nt-bulged substrate binding arm in the stem III (buRz28) were
      able to cleave TEL-AML1 chimeric RNA specifically at sites close to the junction
      in vitro, without cleaving the normal TEL and AML1 RNA. Single-turnover kinetic
      analysis under enzyme-excess condition revealed that the buRz28 is superior to
      the Dz26 in terms of substrate binding and RNA-cleavage. In conjunction with
      current progress in a gene-delivery technology, the designed oligonucleotides
      that specifically cleave the TEL-AML1 chimeric mRNA are hoped to be applicable
      for the treatment of ALL in vivo.

PMID- 18627770
TI  - Clozapine-induced myocarditis: role of catecholamines in a murine model.
AB  - Clozapine, an atypical antipsychotic, is very effective in the treatment of
      resistant schizophrenia. However, cardiotoxicity of clozapine, particularly in
      young patients, has raised concerns about its safety. Increased catecholamines
      have been postulated to trigger an inflammatory response resulting in
      myocarditis, dilated cardiomyopathy, and death, although this has not yet been
      thoroughly studied. Here, we used the mouse to study whether clozapine
      administration could cause adverse myocarditis associated with an increase in
      catecholamines. Male Balb/C mice, age ~6 weeks, were administered 5, 10 or 25
      mg/kg clozapine daily for 7 and 14 days; one group was administered 25 mg/kg
      clozapine plus 2 mg/kg propranolol for 14 days. Saline-treated mice served as
      controls. Heart sections were stained with hematoxylin and eosin for
      histopathological examination. Plasma catecholamines were measured with HPLC.
      Myocardial TNF-alpha concentrations were determined by ELISA. Histopathology of
      clozapine-treated mice showed a significant dose-related increase in myocardial
      inflammation that correlated with plasma catecholamine levels and release of TNF
      alpha. Propranolol significantly attenuated these effects. A
      hypercatecholaminergic state induced by clozapine could explain the occurrence of
      myocarditis in some patients. Our data suggest that a beta-adrenergic blocking
      agent may be effective in reducing the incidence and severity of clozapine
      induced myocarditis.

PMID- 18627771
TI  - Modulation of corneal and stromal matrix metalloproteinase by the mannose-induced
      Acanthamoeba cytolytic protein.
AB  - The involvement of the mannose-induced Acanthamoeba cytopathic protein (MIP-133)
      in tissue injury and activation of metalloproteinase of corneal and stromal cells
      was examined in vitro. Activation of MMP-1, MMP-2, MMP-3, and MMP-9 induced by
      MIP-133 on human corneal epithelial and stromal cell cultures was examined by
      reverse transcriptase polymerase chain reaction (RT-PCR) and ELISA. MMP-1, MMP-2,
      MMP-3, and MMP-9 mRNA were expressed in both cultured human corneal epithelial
      and stromal cells. When the epithelial cells were exposed to MIP-133 protein, the
      mRNA expression for MMP-1 and MMP-9 was unchanged. However, the transcript for
      MMP-2 and MMP-3 was decreased by 2-fold. By contrast, the expression of MMP-2 and
      MMP-3 was significantly upregulated (2- to 4-fold) in the corneal stromal cells
      1, 4, and 8h after MIP-133 stimulation. At the protein level, there was no
      significant difference in the level of MMPs between the corneal epithelial cells
      before and after stimulation with MIP-133. By contrast, the levels of MMP-2 and
      MMP-3 were significantly higher in the corneal stromal cells stimulated with MIP
      133. The supernatants from corneal stromal cells stimulated with MIP-133 were
      incubated with PMSF and MIP-133 antibody and the level of MMP-2 was measured by
      ELISA. Activation of MMP-2 by MIP-133 was inhibited in the supernatants
      pretreated with the serine protease inhibitor, PMSF, and anti-MIP-133.
      Supernatants pretreated with the cysteine protease inhibitor E6 or control
      antibody produced the same amount of MMP-2 as the untreated supernatants. To
      verify possible homology between MMPs and Acanthamoeba castellanii proteases, the
      mRNA from A. castellanii was prepared and analyzed for the expression of MMP
      genes by PT-PCR. The results showed that A. castellanii did not express mRNA for
      MMP-1, MMP-2, MMP-3, or MMP-9. Thus, A. castellanii mRNA does not cross-react
      with human MMPs. Furthermore, ELISA was used to determine the cross-reactivity of
      MMP antibodies with the MIP-133 protein. Monoclonal antibodies against MMPs did
      not cross-react with either the MIP-133 protein or BSA (negative control
      antigen). The results indicate that the MIP-133 protein modulates MMP-2 and -3
      expression differently in human corneal epithelial and stromal cells.

PMID- 18627772
TI  - Surface expression of metabotropic glutamate receptor variants mGluR1a and
      mGluR1b in transfected HEK293 cells.
AB  - Class C G-protein coupled receptors form obligatory dimers. Metabotropic
      glutamate receptors (mGluRs) are found commonly as homodimers. Alternative
      splicing of mGluR1 gene results in vivo in the expression of a long variant
      mGluR1a and at least two short variants mGluR1b and d. The amino acid sequences
      diverge within their carboxyl-termini six amino acid residues following RRKK
      motif. This four basic residue sequence was shown to have pronounced impact on
      function and trafficking of the short variants, while for mGluR1a the long C
      terminus reduces the effects caused by presence of the RRKK motif. Here we
      investigated consequences of interactions between long mGluR1a and short mGluR1b
      variants. Our results show that mGluR1a interferes with mGluR1b trafficking to
      the cell surface in HEK293 transfected cells. Expression of a mGlu1a mutant
      incapable of activating G-proteins with mGluR1b mutated in the glutamate binding
      site led to the formation of a functional heterodimer. Moreover, we show that
      swapping long mGluR1a and/or short mGluR1b C-termini with corresponding regions
      in chimerical GB1 and GB2 gamma-amino butyric acid b (GABAb) receptor subunits do
      not exclude heterodimerization. These data reveal that the C-terminal ends of
      mGluR1 do not control subunit association, such that mGluR1 dimers with two
      distinct C-termini can form and function properly.

PMID- 18627773
TI  - A review of the evolution of animal colour vision and visual communication
      signals.
AB  - The visual displays of animals and plants are often colourful, and colour vision
      allows animals to respond to these signals as they forage for food, choose mates
      and so-forth. This article discusses the evolutionary relationship between
      photoreceptor spectral sensitivities of four groups of land animals--birds,
      butterflies, primates and hymenopteran insects (bees and wasps)--, the colour
      signals that are relevant to them, and how understanding is informed by models of
      spectral coding and colour vision. Although the spectral sensitivities of
      photoreceptors are known to vary adaptively under natural selection there is
      little evidence that those of hymenopterans, birds and primates are specifically
      adapted to the reflectance spectra of food plants or animal visual signals. On
      the other hand, the colours of fruit, flowers and feathers may have evolved to be
      more discriminable for the colour vision of their natural receivers than for
      other groups of animals. Butterflies are unusual in that they have enjoyed a
      major radiation in receptor numbers and spectral sensitivities. The reasons for
      the radiation and diversity of butterfly colour vision remain unknown, but may
      include their need to find food plants and to select mates.

PMID- 18627775
TI  - Tolerability and effects of oral Delta9-tetrahydrocannabinol in older adolescents
      with marijuana use disorders.
AB  - OBJECTIVE: The tolerability and effects of oral Delta9-tetrahydrocannabinol (THC)
      have been previously investigated in adult marijuana abusers. However, no studies
      have included adolescent participants. This double-blind laboratory study
      investigated the tolerability and effects of oral THC in a group of older
      adolescents with marijuana use disorders. METHODS: Eight participants (ages 16-21
      years), smoking an average of 5.2 days/week and 2.5 "joints"/day, completed this
      four-session study, during which they received one of four oral THC doses (0,
      2.5, 5, 10 mg) each session. Administration of oral THC doses was counterbalanced
      across participants. During each session, participants completed the Digit-Symbol
      Substitution Task (DSST) and subjective-effect ratings at baseline and 1, 2, and
      3 h after oral THC administration. RESULTS: Oral THC (5 mg and 10 mg) increased
      several "positive" subjective-effect ratings (e.g., "Good Drug Effect"), while
      producing no significant effects on cardiovascular measures, DSST performance, or
      "negative" subjective-effect ratings. CONCLUSIONS: These results indicate that
      oral THC was well tolerated and suggest further study of this medication in
      adolescent marijuana abusers.

PMID- 18627776
TI  - Inhibition of cyclin-dependent kinase 5 by roscovitine impairs memory
      consolidation and reconsolidation in the day-old chick.
AB  - Cyclin-dependent kinase 5 (CDK-5) is reported to phosphorylate the NMDA receptor
      prior to the induction of long-term potentiation (LTP), among its many other
      effects. Application of CDK-5 inhibitors disrupts LTP and results in impaired
      task acquisition in behaving animals. In this study, we investigated the effect
      of exogenously applied roscovitine, a potent CDK-5 inhibitor, on consolidation
      and reconsolidation processes in day-old male chicks. New Hampshire x White
      leghorn cockerels were trained using a modified version of the passive avoidance
      learning task. Intracranial injections of roscovitine (2.5 microM) administered
      immediately after training induced a memory deficit that evolved from 5-minute
      post-training and persisted until at least 24 h following training. Injections of
      roscovitine (2.75 microM) administered immediately after the reminder trial
      induced a memory deficit observed by 30-minute post-reminder which had resolved
      by 24 h following the reminder. The comparison between consolidation and
      reconsolidation demonstrates differences both in the time of the onset of the
      memory deficit as well as in the permanence of this deficit. The results suggest
      an important, although different role for CDK-5 in consolidation and
      reconsolidation processes following passive avoidance learning.

PMID- 18627774
TI  - Attention and active vision.
AB  - Visual perception results from the interaction of incoming sensory signals and
      top down cognitive and motor signals. Here we focus on the representation of
      attended locations in parietal cortex and in earlier visual cortical areas. We
      review evidence that these spatial representations are modulated not only by
      selective attention but also by the intention to move the eyes. We describe
      recent experiments in monkey and human that elucidate the mechanisms and
      circuitry involved in updating, or remapping, the representations of salient
      stimuli. Two central ideas emerge. First, selective attention and remapping are
      closely intertwined, and together contribute to the percept of spatial stability.
      Second, remapping is accomplished not by a single area but by the participation
      of parietal, frontal and extrastriate cortex as well as subcortical structures.
      This neural circuitry is distinguished by significant redundancy and plasticity,
      suggesting that the updating of salient stimuli is fundamental for spatial
      stability and visuospatial behavior. We conclude that multiple processes and
      pathways contribute to active vision in the primate brain.

PMID- 18627777
TI  - Effects of sucrose, glucose and fructose on peripheral and central appetite
      signals.
AB  - In the Western world, consumption of soft drinks has increased the last three
      decades and is partly responsible for the epidemic-like increase in obesity. Soft
      drinks, originally sweetened by sucrose, are now sweetened by other caloric
      sweeteners, such as fructose. In this study, we investigated the short-term
      effect of sucrose, glucose or fructose solutions on food intake and body weight
      in rats, and on peripheral and central appetite signals. Rats received water
      containing either of the sugars and standard rat chow for two weeks. Rats
      receiving water alone and standard chow were controls. All rats offered the sugar
      solutions increased their total caloric intake. The increased caloric intake
      occurred despite the fact that the rats offered either of the sugar solutions
      consumed less chow. As a consequence of the increased caloric intake, the sugar
      drinking rats had elevated serum levels of free fatty acids, triglycerides and
      cholesterol. In addition, consuming sugar solutions resulted in increased serum
      leptin, decreased serum PYY and down-regulated hypothalamic NPY mRNA. Serum
      ghrelin was increased in rats receiving fructose solution. Moreover, consumption
      of sucrose or fructose solution resulted in up-regulated hypothalamic CB1 mRNA.
      Hypothalamic POMC mRNA was down-regulated in rats receiving glucose or fructose.
      In conclusion, consumption of glucose, sucrose or fructose solution results in
      caloric overconsumption and body weight gain through activation of hunger signals
      and depression of satiety signals as well as activation of reward components. The
      weight-promoting effect of these sugar solutions may possibly be ameliorated by
      the down-regulation of NPY mRNA and increased serum leptin.

PMID- 18627778
TI  - Matrix-assisted laser desorption ionisation-time-of of-flight mass spectrometry
      of intact cells allows rapid identification of Burkholderia cepacia complex.
AB  - The present study examined the potential of intact-cell matrix-assisted laser
      desorption ionisation-time-of-flight mass spectrometry (MALDI-TOF MS) for a rapid
      identification of Burkholderia cepacia complex (Bcc) bacteria using an Applied
      Biosystems 4700 Proteomics Analyser. Two software packages were used to analyse
      mass profiles based on densitometric curves and peak positions. The 75 strains
      examined, represented the nine established Bcc species and some commonly
      misidentified species, closely related or biochemically similar to Bcc and
      relevant in the context of cystic fibrosis microbiology. All Bcc strains
      clustered together, separated from non-Bcc strains. Within Bcc, most Bcc strains
      grouped in species specific clusters, except for Burkholderia anthina and
      Burkholderia pyrrocinia strains which constituted a single cluster. The present
      study demonstrates that MALDI-TOF MS is a powerful approach for the rapid
      identification of Bcc bacteria.

PMID- 18627779
TI  - Rapid culture-based methods for drug-resistance detection in Mycobacterium
      tuberculosis.
AB  - Tuberculosis still represents a major public health problem, especially in low
      resource countries where the burden of the disease is more important. Multidrug
      resistant and extensively drug drug-resistant tuberculosis constitute serious
      problems for the efficient control of the disease stressing the need to
      investigate resistance to first- and second-line drugs. Conventional methods for
      detecting drug-resistance in Mycobacterium tuberculosis are slow and cumbersome.
      The most commonly used proportion method on Lowenstein-Jensen medium or
      Middlebrook agar requires a minimum of 3-4 weeks to produce results. Several new
      approaches have been proposed in the last years for the rapid and timely
      detection of drug-resistance in tuberculosis. This review will address phenotypic
      culture-based methods for rapid drug susceptibility testing in M. tuberculosis.

PMID- 18627780
TI  - Random tag insertions by Transposon Integration mediated Mutagenesis (TIM).
AB  - Transposon Integration mediated Mutagenesis (TIM) is a broadly applicable tool
      for protein engineering. This method combines random integration of modified
      bacteriophage Mu transposons with their subsequent defined excision employing
      type IIS restriction endonuclease AarI. TIM enables deletion or insertion of an
      arbitrary number of bases at random positions, insertion of functional sequence
      tags at random positions, replacing randomly selected triplets by a specific
      codon (e.g. scanning) and site-saturation mutagenesis. As a proof of concept a
      transposon named GeneOpenerAarIKan was designed and employed to introduce 6xHis
      tags randomly into the esterase EstC from Burkholderia gladioli. A TIM library
      was screened with colony based assays for clones with an integrated 6xHis tag and
      for clones exhibiting esterase activity. The employed strategy enables the
      isolation of randomly tagged active enzymes in single mutagenesis experiments.

PMID- 18627781
TI  - The interactive effect of achievement motivation and task difficulty on mental
      effort.
AB  - The interactive effect of achievement motivation and task difficulty on invested
      mental effort, postulated by Humphreys and Revelle [Humphreys, M.S., Revelle, W.,
      1984. Personality, motivation, and performance: a theory of the relationship
      between individual differences and information processing. Psychol. Rev. 91, 153
      184], was examined using behavioral, subjective, and effort-related physiological
      measures. Eighteen approach-driven participants and 18 avoidance-driven
      participants were selected based on their motive to achieve success scores and
      their motive to avoid failure scores. A 2x3 factorial design was used, with three
      levels of task difficulty. As expected, approach-driven participants performed
      better and had a stronger decrease of midfrequency band of heart rate variability
      than avoidance-driven participants, especially during the difficult task. These
      results support the interactive effect of achievement motivation and task
      difficulty on invested mental effort.

PMID- 18627782
TI  - Suppression of the auditory N1 event-related potential component with
      unpredictable self-initiated tones: evidence for internal forward models with
      dynamic stimulation.
AB  - Internally operating forward model mechanisms enable the organism to discriminate
      the sensory consequences of one's own actions from other sensory events. The
      present event-related potential (ERP) study compared the processing of self
      initiated tones with the processing of externally-initiated but otherwise
      identical tones. In different conditions, frequency and onset of the sound were
      either predictable or unpredictable. The amplitudes of the N1 component of the
      ERP for the self-initiated relative to the ones for externally-initiated sounds
      were significantly attenuated even when the particular frequency or sound onset
      could not be predicted by the subject. These results support internal forward
      model mechanisms which dynamically predict the sensorial consequences of ones own
      motor acts even in face of uncertainties with respect to the frequency of the
      sound and its onset. Moreover, the attenuation effect was reduced when the
      frequency was unpredictable suggesting that it is easier to discriminate a self
      initiated sound with exact foreknowledge.

PMID- 18627783
TI  - Cover story. Non-viral gene and drug delivery.

PMID- 18627785
TI  - Enzymatic reduction of labile iron by organelles of the rat liver. Superior role
      of an NADH-dependent activity in the outer mitochondrial membrane.
AB  - The enzymatic system mainly responsible for the reduction of labile iron ions in
      mammalian cells is still unknown. Using isolated organelles of the rat liver,
      i.e. mitochondria, microsomes, nuclei and the cytosol, we here demonstrate that
      Fe(III), added as Fe(III)-ATP complex, is predominantly reduced by an NADH
      dependent enzyme system associated with mitochondria (65% of the overall
      enzymatic Fe(III) reduction capacity within liver cells). Microsomes showed a
      significantly smaller Fe(III) reduction capacity, whereas the cytosol and nuclei
      hardly reduced Fe(III). Studying the mitochondrial iron reduction, this NADH
      dependent process was not mediated by superoxide, ascorbic acid, or NADH itself,
      excluding low-molecular-weight reductants. No evidence was found for the
      involvement of complex I and III of the respiratory chain. Submitochondrial
      preparations revealed the highest specific activity reducing Fe(III) in the outer
      membrane fraction. In conclusion, an NADH-dependent mitochondrial enzyme system,
      most likely the NADH-cytochrome c reductase system, located at the outer
      membrane, should decisively contribute to the enzymatic reduction of labile iron
      within liver cells, especially under pathological conditions.

PMID- 18627784
TI  - Peptide-modified vectors for nucleic acid delivery to neurons.
AB  - Neuron-targeted nucleic acid delivery systems are important technologies for
      realizing the potential of gene therapy for nervous system disorders. However,
      neurons are difficult cells to transfect using non-viral vectors due in part to
      the specific and unique delivery challenges present in these cells. We have
      investigated several bioactive peptides for their ability to assist in overcoming
      delivery barriers in mammalian cells. We summarize here our recent progress in
      developing and applying peptide-modified polycations for nucleic acid delivery.
      In addition, we present data demonstrating the potential of using multicomponent,
      peptide-modified polycations for nucleic acid delivery to neurons.

PMID- 18627786
TI  - Antiproliferative activities of resveratrol and related compounds in human
      hepatocyte derived HepG2 cells are associated with biochemical cell disturbance
      revealed by fluorescence analyses.
AB  - Resveratrol is a well known polyphenol largely produced in grapevine. It is a
      strong antioxidant and a free radical scavenger. It exhibits several beneficial
      effects for health including cancer. Resveratrol antioxidant activity is
      essential in the prevention of chemical-induced cancer by inhibiting initiation
      step of carcinogenesis process but it is also considered to inhibit cancer
      promotion and progression steps. While the effects of resveratrol on cancer cells
      are widely described, the data available on the antiproliferative potential of
      resveratrol derivatives remain weak. Nevertheless, resveratrol analogs could
      exhibit stronger potentials than the parent molecule. So, we compared the
      cellular effects of trans-resveratrol, trans-epsilon-viniferin and their
      respective acetate derivatives, as well as a polyphenol mixture extracted from
      grapevine shoots, called vineatrol. We studied their abilities to interfere with
      cell proliferation, their uptake and their effects on parameters of cellular
      state in human hepatoma cells (HepG2). Cell growth experiments show that
      resveratrol triacetate presents a slightly better antiproliferative potential
      than resveratrol. The dimer epsilon-viniferin,as well as its pentaacetate analog,
      is less powerful than resveratrol, although a similar uptake kinetics in cells.
      Interestingly, among the tested polyphenols, vineatrol is the most potent
      solution, indicating a possible synergistic effect of both resveratrol and
      epsilon-viniferin. We took advantage of the fluorescence properties of these
      compounds to evidence cellular uptake by using flow cytometry. In addition, by
      competition assay, we demonstrate that resveratrol triacetate enters in hepatic
      HepG2 cells by the same way as resveratrol. By autofluorescence in situ
      measurement we observed that resveratrol and related compounds induce deep
      changes in cells activity. These changes occur mainly by increasing NADPH cell
      content and the number of green fluorescent cytoplasmic granular structures which
      may be related to an induction of detoxifying enzyme mechanisms.

PMID- 18627787
TI  - Two distinctly altered cellular responses to DNA double-strand breaks in human
      neuroblastoma.
AB  - Neuroblastoma (NB), the most common extracranial solid tumors in children,
      presents with numerous genetic abnormalities that accumulate in a very short
      lifetime. To better understand this process, we have induced DNA double-strand
      breaks in NB cell lines and analyzed the activation of the ATM-H2AX/Chk2-p53
      signaling pathway. We have found that NB cells could be classified into two
      distinct groups. The first group strongly expressed activated Chk2, displayed an
      important sub-G1 population, expressed very low levels of p21, and exhibited an
      attenuated G1 arrest. Conversely, the second group weakly expressed Chk2 pT68,
      displayed no sub-G1 cell population, strongly expressed p21, and exhibited a
      functional G1 arrest. These findings were independent of the MYCN amplification
      or p53 status of the NB cell lines tested. Interestingly, most p21 weakly
      expressing NB cells expressed neuron-specific enolase and Bcl2, two markers of N
      type NB cells, but did not express vimentin, a marker of S-type NB cells. The
      expression profile was reversed in the p21 strongly expressing NB cells which
      highly expressed vimentin. Along with additional data, our findings lead us to
      propose that N-type-like NB cells would survive under stress conditions by
      antagonizing the Chk2-dependent apoptosis pathway, whereas S-type-like NB cells
      would survive by down-regulating Chk2 expression to facilitate the crossing of
      the senescence barrier.

PMID- 18627788
TI  - GABA-mediated inhibition correlates with orientation selectivity in primary
      visual cortex of cat.
AB  - Orientation selectivity is an important emergent property of neurons in the
      primary visual cortex, and inhibition is thought to play an important role in
      establishing this selectivity. But the relationship between strength of
      inhibition and orientation selectivity is unclear. To investigate this
      relationship, we electrophoretically applied the inhibitory transmitter GABA and
      the GABA(A) antagonist bicuculline on the same individual area 17 neurons in
      anesthetized cats. Neurons were classified as weakly orientation-selective,
      moderately orientation-selective, or strongly orientation-selective, according to
      the values of an orientation bias index. Orientation bias, half-width of the
      tuning curve at half-height and an orientation-specificity index (orthogonal to
      optimal ratio) were compared with or without GABA and bicuculline administration.
      GABA improved orientation selectivity with the greatest effects on weakly
      orientation-selective cells, smaller effects on moderately orientation-selective
      cells, and minimal effects on strongly orientation-selective cells; bicuculline
      diminished orientation selectivity the most on moderately and strongly
      orientation-selective cells, with minimal effects on weakly orientation-selective
      cells. We also found that orientation selectivity correlated with the level of
      neurons' spontaneous activity. These results suggest that the degree of
      orientation selectivity of an area 17 neuron correlates with its endogenous
      inhibition strength, and that GABAergic inhibition can bi-directionally regulate
      orientation selectivity. This correlation indicates that GABA-mediated inhibition
      plays an important role in establishing sharp orientation selectivity of
      individual neurons.

PMID- 18627789
TI  - Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube
      formation in human endothelial cells through LPA(1/3), COX-2, and NF-kappaB
      activation- and EGFR transactivation-dependent mechanisms.
AB  - Lysophosphatidic acid (LPA) is a lipid bioactive mediator which binds to G
      protein-coupled receptors and activates a variety of cellular functions. LPA
      modulates multiple behaviors in endothelial cells, including cell proliferation
      and migration, capillary-like tube formation in vitro, activation of proteases,
      interactions with leukocytes, and expressions of inflammation-related genes,
      thereby regulating vessel formation. LPA has been reported to modulate the
      angiogenesis process. However, the role of LPA in the lymphangiogenesis process
      has not been studied. In this study, we showed that LPA upregulated vascular
      endothelial growth factor-C (VEGF-C) mRNA expression in human umbilical vein
      endothelial cells (HUVECs) and subsequent endothelial cell tube formation in
      vitro and in vivo. These enhancement effects were LPA(1)- and LPA(3)-dependent
      and required cyclooxygenase-2 (COX-2), endothelial growth factor receptor (EGFR)
      transactivation and activation of nuclear factor kappaB (NF-kappaB). Moreover,
      LPA induced the protein expressions of the lymphatic markers, Prox-1, LYVE-1, and
      podoplanin, in HUVECs, and these enhancement effects were dependent on LPA(1) and
      LPA(3) activation and EGFR transactivation. Our results demonstrated that LPA
      might regulate VEGF-C and lymphatic marker expression in endothelial cells, which
      contributes to endothelial cell tube formation in vitro and in vivo, thus
      facilitating endothelial cell participation in the lymphangiogenesis process.
      This study clarifies the signaling mechanism of LPA-regulated VEGF-C expression
      and lymphatic marker expressions in endothelial cells, which suggest that LPA may
      be a suitable target for generating therapeutics against lymphangiogenesis and
      tumor metastasis.

PMID- 18627790
TI  - Erythropoietin receptor-mediated Egr-1 activation: structural requirements and
      functional implications.
AB  - The transcription factor Egr-1 is encoded by an immediate early response gene and
      has been shown to be a key regulator in the induction of apoptosis, mitogenesis
      and differentiation. It is rapidly induced by different stimuli including the
      glycoprotein hormone erythropoietin. In this report, we analyse the role of
      different erythropoietin receptor substructures for the activation of Egr-1 and
      the functional consequences of Egr-1 overexpression in the erythroleukemic cell
      line ELM-I-1. The investigation of receptor variants revealed that the activity
      of JAK2 and the phosphorylation of receptor tyrosine residues are essential
      preconditions for the ability to target Egr-1. Furthermore, we observed a close
      correlation of the abilities of receptors to activate the Ras-MAPK pathway and
      Egr-1. Using mass spectrometry we identified the Ras-GTPase-activating protein
      SH3-domain-binding protein 1 (G3BP-1), a component of the Ras network of
      proteins, as an Egr-1 interacting protein in EPO stimulated ELM-I-1 cells. The
      overexpression of Egr-1 in these cells resulted in an enhanced rate of
      spontaneous erythroid differentiation.

PMID- 18627791
TI  - Apolipoprotein A-I from striped bass (Morone saxatilis) demonstrates
      antibacterial activity in vitro.
AB  - HDL and apolipoprotein A-I from teleostean fishes demonstrate in vitro activity
      against gram-positive and gram-negative bacteria. In this study, we purified ApoA
      1 from striped bass (Morone saxatilis) plasma and examined its in vitro
      antibacterial activity against Streptococcus sp., Escherichia coli, and
      Mycobacterium marinum. In addition, we obtained sequence for a putative striped
      bass ApoA-1 gene, which when translated contained the identical sequence
      generated from N-terminal sequencing of the purified ApoA-1. The predicted
      secondary and tertiary structures contained the characteristic proline residues
      and high alpha-helical content conserved between mammals and fishes. Purified
      ApoA-1 exhibited antibacterial activity against the bacteria assayed.
      Concentrations of 125 microg/mL for E. coli, 250 microg/mL for Streptococcus sp.,
      and 250 microg/mL for M. marinum, inhibited bacterial growth by 50% compared to
      control. ApoA-1 plasma concentrations in experimental and wild fish ranged from
      undetectable levels to greater than 5 mg/mL, indicating that striped bass ApoA-1
      is an effective antibacterial agent at concentrations below the range of
      physiological concentrations in striped bass plasma. We therefore conclude that
      ApoA-1 could play a role in innate defense against bacterial pathogens in striped
      bass.

PMID- 18627792
TI  - The role of the anterior insular cortex in ictal vomiting: a stereotactic
      electroencephalography study.
AB  - Ictal vomiting is a rare manifestation most often associated with right temporal
      lobe epilepsy. The implication of the anterior insula in the occurrence of this
      symptom has been suggested based on the role of this region in swallowing and on
      the observation that electrical insular stimulation can elicit nausea and
      vomiting. We report the first case, to our knowledge, of a patient presenting
      with ictal vomiting who underwent bilateral intracranial exploration including
      insular depth electrodes. The seizure onset zone was localized in the left
      temporomesial structures, but the occurrence of ictal vomiting correlated in time
      with a discharge affecting exclusively the anterior part of both insular lobes.
      It is concluded that the occurrence of ictal vomiting reflects a propagation of
      the discharge to the insular cortex. Observation of this symptom at the very
      onset of the seizures in a patient with temporal lobe epilepsy is highly
      suggestive of an insular seizure onset zone.

PMID- 18627793
TI  - Evaluation of the responsiveness of the Impact of Pediatric Epilepsy Scale.
AB  - The Impact of Pediatric Epilepsy Scale (IPES) is an epilepsy-specific, health
      related quality of life (HRQOL) questionnaire that is brief, accurate, and valid
      and assesses the influence of epilepsy on the child and family. This study
      prospectively investigates the responsiveness of the IPES, 3 years after the IPES
      questionnaire was initially validated. The same parents or caregivers completed
      the IPES. Changes in IPES scores were compared with changes in epilepsy severity.
      IPES Total scores were highly related to change in seizure severity (Wilks'
      lambda F (3, 11)=5.0, P<0.001). Those whose seizure severity decreased had
      decreased IPES scores (indicating improvement of HRQOL); those with increased
      seizure severity had increased IPES scores and reported poorer HRQOL; and those
      with no change in seizure severity had no change in the IPES score and no change
      in HRQOL. In conclusion, the IPES is useful for measurement of a child's epilepsy
      specific HRQOL during treatment and is responsive to changes in epilepsy severity
      over time.

PMID- 18627794
TI  - A review of recent reports on autism: 1000 studies published in 2007.
AB  - From 1000 studies published in 2007 on all aspects of autism, those that reached
      clear conclusions or included quantitative data were selected for this review.
      Possible etiologies include elemental metals, especially the inconsistent
      evidence regarding mercury from the vaccine preservative thimerosal, not used
      after 2001, and chromosomes and genes with the conclusion that autism has a
      complex genetic architecture. Also, various parental conditions are considered,
      as are many different abnormalities in the central nervous system, especially
      underconnectivity within the cortex. Furthermore, deficiencies in mirror neurons
      have been proposed, leading to the "theory of mind" explanation that autistic
      children tend to disregard others. In addition, various global deficiencies, like
      an increase in inhibitory synaptic transmission, are proposed. Characteristics of
      these children include selective (inward) attention; underresponsiveness;
      stereotyped repetitive motor behavior; increased head size, weight, and height;
      various cognitive and communicative disorders; and also epilepsy. Therapy has
      emphasized risperidone, but some atypical antipsychotic medications have been
      helpful, as have robotic aids, massage, hyperbaric oxygen, and music. Nearly
      every conceivable problem that a child could have can be observed in these
      unfortunate children.

PMID- 18627795
TI  - Acute effects of diflubenzuron on the freshwater fish Prochilodus lineatus.
AB  - The effects of diflubenzuron (DFB), an insecticide to control ectoparasites in
      fish farms, on muscle acetylcholinesterase (AChE), detoxifying and antioxidant
      enzymes, hematological and physiological parameters, and liver histopathology
      were evaluated in Prochilodus lineatus after 6, 24 and 96 h of exposure to 25 mg
      L(-1) of DFB. The insecticide caused a reduction in the number of erythrocytes
      and hemoglobin content after 96 h exposure, probably due to hemolysis.
      Hyperglycemic response indicated energy mobilization, and may have contributed to
      the increase in osmolarity after 96 h exposure to DFB. The induction of
      glutathione-S-transferase (GST) and catalase activities in liver pointed to the
      activation of xenobiotic metabolic pathways and antioxidant defenses. The
      decrease in muscle AChE at all experimental times showed that DFB is an AChE
      inhibitor. In addition, DFB induced hepatic alterations that might impair normal
      liver functions. These results show that DFB can cause health disorders in fish
      and further studies are required to better define its safe use in aquaculture.

PMID- 18627796
TI  - Exposure to coal combustion residues during metamorphosis elevates corticosterone
      content and adversely affects oral morphology, growth, and development in Rana
      sphenocephala.
AB  - Coal combustion residues (CCRs) are documented to negatively impact oral
      morphology, growth, and development in larval amphibians. It is currently unclear
      what physiological mechanisms may mediate these effects. Corticosterone, a
      glucocorticoid hormone, is a likely mediator because when administered
      exogenously it, like CCRs, also negatively influences oral morphology, growth,
      and development in larval amphibians. In an attempt to identify if corticosterone
      mediates these effects, we raised larval Southern Leopard Frogs, Rana
      sphenocephala, on either sand or CCR substrate and documented effects of sediment
      type on whole body corticosterone, oral morphology, and time to and mass at key
      metamorphic stages. Coal combustion residue treated tadpoles contained
      significantly more corticosterone than controls throughout metamorphosis.
      However, significantly more oral abnormalities occurred early in metamorphosis
      when differences in corticosterone levels between treatments were minimal.
      Overall, CCR-treated tadpoles took significantly more time to transition between
      key stages and gained less mass between stages than controls, but these
      differences between treatments decreased during later stages when corticosterone
      differences between treatments were greatest. Our results suggest endogenous
      increase in corticosterone content and its influence on oral morphology, growth
      and development is more complex than previously thought.

PMID- 18627798
TI  - Teamwork in China--is it any different?

PMID- 18627797
TI  - Validation of guinea pig model of allergic rhinitis by oral and topical drugs.
AB  - Ovalbumin-induced guinea pig model of rhinitis was assessed for its utility in
      the studies of rhinitis. Systemic sensitization and challenge with ovalbumin
      induced rhinitis symptoms and an increase in anti-OVA-IgE and IgG titers,
      positive skin reactions and nasal lavage IL-4 concentration. Histopathology of
      nasal mucosa showed infiltration of eosinophils and other inflammatory cells
      consistent with the symptoms. Topical sensitization of ovalbumin yielded
      inconsistent symptoms of rhinitis. In systemic sensitization model, repeated
      challenge of ovalbumin caused similar response for at least 3 consecutive
      challenges. The symptoms were affected by relative humidity in the air and dosing
      volume of topical drugs. Sneezing and lacrimation were reduced by acute oral
      administration of the H1 receptor antagonists and steroids or the prophylactic
      oral administration of cysteinyl leukotriene (CysLT1) receptor antagonist
      montelukast or acute topical antihistamines, mast cell stabilizer sodium
      cromoglycate and anticholinergic agent ipratropium bromide, but not by a topical
      steroid. Nose rubbing was reduced significantly by some oral and topical
      antihistamines. Oral steroids offered excellent protection against all symptoms.
      Dexamethasone and montelukast also inhibited nasal lavage IL-4 concentration and
      inflammatory cell infiltration. Treatment with topical steroid fluticasone for 2
      weeks had no effect on sneezing or rubbing. However, it caused complete
      inhibition of congestion. The cyclooxygenase inhibitor indomethacin had no effect
      on symptoms of rhinitis. The adrenergic alpha receptor agonist-decongestant
      oxymetazoline caused reduction in congestion. These results suggest that
      differential responsiveness to symptoms of rhinitis by a new agent can be very
      well profiled in the model in congruence with the mediation pathways and
      mechanism of action of drugs. The model provides complete symptomatic
      characterization of rhinitis and is a good tool for its study.

PMID- 18627799
TI  - Increasing the profile of the care of the older person in the ED: a contemporary
      nursing challenge.
AB  - The numbers of frail older persons using emergency departments are already
      considerable and will continue to increase over time. There are a number of
      issues related to the assessment and care of older patients that are
      significantly different to other patient groups. The traditional emergency
      department (ED) model focusing on rapid triage, treatment and throughput does not
      meet the needs of many older patients, who have complex presentations, and
      require comprehensive assessment and referral. In response to this, there are
      already a number of appropriate and innovative approaches to the care of the
      older patient demonstrated in the literature. Nurses have a crucial role in
      contributing to these approaches and in raising the profile of quality care of
      the older person. Some specific areas that ED nurses can focus on include a more
      comprehensive approach to assessment and discharge planning, improved
      communication with the patient and their personal carers, attention to basic
      nursing care, and making the physical environment safer and less stressful for
      the older patient. While developing collaborations with their aged care nursing
      colleagues is important, emergency nurses need to view care of the older person
      as a central part of their own core business.

PMID- 18627800
TI  - Knowledge of inter-facility transport among emergency nurses in Hong Kong: a
      questionnaire survey.
AB  - INTRODUCTION: Inter-facility transport (IFT) is a dynamic process and its quality
      largely depends on pre-transport preparation, emergency equipment support and
      recognition of possible en route adverse events. This study aims to evaluate
      knowledge of IFT among emergency nurses of three Accident and Emergency
      Departments in Hong Kong. METHODS: Questionnaires were distributed to registered
      nurses of the three departments. Data was sought on participants'
      characteristics, knowledge on equipment preparation and management of en route
      adverse events. Four clinical IFT scenarios were set for participants and answers
      were scored. Measured outcomes were defined as (1) relationships between clinical
      experience and relevant training in IFT with questionnaire results, (2) staff
      knowledge of the equipment carried routinely in ambulances and (3) the en route
      adverse events encountered according to the participants' past experience.
      RESULTS: Participants' test scores ranged from 24 to 37 (out of 40) with a mean
      of 30.6 (95% confidence interval 29.7-31.5). Participants with more clinical
      experience demonstrated significantly better test scores (p<0.05). Most
      participants were familiar with the monitoring devices carried in ambulances but
      were less familiar with the pharmacologic agents and airway devices available
      routinely in Hong Kong ambulances. Thirty participants (59%) had encountered en
      route adverse events in the past. CONCLUSION: Nurses in emergency departments in
      Hong Kong have good knowledge of IFT. Extensive clinical experience is related to
      better IFT knowledge. IFT training for nurses should emphasize available
      ambulance service resources and capabilities.

PMID- 18627801
TI  - Triaging suicidal patients: sifting through the evidence.
AB  - The triaging of individuals who present to general hospital emergency departments
      with suicidal thoughts and behaviours is especially challenging and fraught with
      uncertainty. Although the suicide literature is vast, and risk factor research
      has a long history, there is a dearth of articles that address the "point of
      care" factors that need to be considered in triaging a suicidal patient. In order
      to address this dilemma for nurses performing the triage function, this paper is
      a targeted review of the suicide risk factor literature designed to discern
      factors that may have implications for making a triage determination with the
      intent of improving the accuracy and quality of triage for suicidal patients.
      Contextual and compositional factors suggesting long-term risk; situational,
      precipitating, factors that may impact one's immediate risk; and cues and clues
      to imminent risk are presented along with evidence-based suggestions for
      assessment and safety.

PMID- 18627802
TI  - Family-centred services within Accident and Emergency Departments.
AB  - The concept of children and their families receiving family-centred care when the
      child is unwell is not new. Family-centred care has been examined extensively
      within children's nursing curricula. However, recent policy documents have
      suggested that all child health services, not just children's nursing, should be
      family-centred. The subtle differences between family-centred care and family
      friendly care are identified. The skills for working with children are also
      examined in turn for all ED nurses. Whilst many ideas may not initially appear to
      be new or therefore innovative, a careful evaluation encourages individuals to
      rethink the services that they currently offer to children and their families.

PMID- 18627803
TI  - Emergency care practitioners (ECP): practice and performance in the UK West
      country--a case study.

PMID- 18627804
TI  - More than medical treatment: the patient's first encounter with prehospital
      emergency care.
AB  - A common feature of emergency care services is the short, fragmented encounters
      with great demands for rapid treatment and efficiency. The aim of this study was
      to describe and understand the patient's first encounter with prehospital
      emergency care as experienced by the patient and the first responders. A
      lifeworld perspective was used in four different traumatic situations. The data
      consisted of 18 unstructured interviews with patients and first responders. The
      phenomenological analysis showed that the concept of lifesaving means more than
      just upholding vital functions. The patient needs to retain his/her identity by
      means of a communicative contact, to be confirmed in the lived encounter and to
      recapitulate the elapsed time of the unexpected event in order to regain a state
      of equilibrium. Five constituents further described the variations of the
      patients' first encounter; the encounter with the helpless injured body, the
      confirming existential encounter, the encounter while waiting, the lived
      encounter and the recapitulated encounter. This finding highlights the importance
      of a new understanding about empowering the patient with narratives throughout
      the whole caring process. There are also implications for educating personnel and
      students in emergency care about the first encounter with the patient in
      emergency care where the senses, the time and the narrative are essential
      elements that are unique for each person.

PMID- 18627806
TI  - Workloads in Australian emergency departments a descriptive study.
AB  - OBJECTIVE: This study aimed to identify the current workload of clinical nurses,
      managers and educators in Australian Emergency Departments according to the
      classification of the department Additionally the relationship of experienced to
      inexperienced clinical staff was examined. DESIGN AND SETTING: A descriptive
      research method utilising a survey distributed to 394 Australian Emergency
      departments with a 21% response rate. MAIN OUTCOME MEASURE(S): Nursing workloads
      were calculated and a ratio of nurse to patient was established. The ratios
      included nurse to patient, management and educators to clinical staff.
      Additionally the percentage of junior to senior clinical staff was also
      calculated. RESULTS: Across all categories of emergency departments the mean
      nurse:patient ratios were 1:15 (am shift), 1:7 (pm shift) and 1:4 (night shift).
      During this period an average of 17.1% of attendances were admitted to hospital.
      There were 27 staff members for each manager and 23.3 clinical staff for each
      educator. The percentage of junior staff rostered ranged from 10% to 38%.
      CONCLUSION: Emergency nurses cannot work under such pressure as it may compromise
      the care given to patients and consequently have a negative effect on the nurse
      personally. However, emergency nurses are dynamically adjusting to the workload.
      Such conditions as described in this study could give rise to burnout and
      attrition of experienced emergency nurses as they cannot resolve the conflict
      between workload and providing quality nursing care.

PMID- 18627805
TI  - An analysis of use of crowd medical services at an English football league club.
AB  - AIM: Although crowd medical services in English league football are common, there
      is little data examining the use of such services. The aim of this study was to
      provide detailed data by examining the usage of the Crowd Medical Service at a
      First Division Football Club (Millwall FC) over six Football League seasons. This
      usage has implications in terms of resources, provision of level of service and
      training needs of staff. METHODS: A prospective data collection form was designed
      and used to capture all episodes of care over the length of six football league
      seasons, each approximately 9 months in duration which resulted in a census of
      activity. This included episodes that did not normally require detailed
      documentation for statutory purposes, such as informal advice. RESULTS: There
      were 445 episodes of care recorded over 146 home games. Over six years
      presentation was consistent. This gives a mean of 3.14 episodes per game (2.7
      4.1). There is little research in this area and so it is difficult to compare
      uptake with other clubs. The episodes of care were broadly grouped into medical
      (67.0%) or injury (33.0%). Most of those presenting did so with non-emergent (pre
      existing) medical problems or minor injuries. Staff (for example Stewards) made
      up 44% of consultations. One hundred and eight people had a primary and secondary
      reason for presenting. Such episodes are more time consuming and in turn have an
      impact on resources. Some stated they had presented because of ease of access to
      the service, they found access to their General Practitioner (GP) difficult or
      were not registered with a GP at all. CONCLUSION: The principal focus of a crowd
      medical service is to manage a major incident and medically emergent spectators.
      The majority of presentations were minor injuries and pre-existing medical
      conditions. In addition staff make up a significant proportion of the users. Some
      re-focussing of guidance is therefore necessary if these results are typical of
      English League Football. In turn this reflects a need for more education in the
      management of minor injuries and chronic disease management and recognition in
      training and service provision.

PMID- 18627807
TI  - Enlarged uvula (Quincke's Oedema)--a side effect of inhaled cocaine?--A case
      study and review of the literature.

PMID- 18627808
TI  - Neurons in the third abdominal ganglion of the early postnatal crayfish: a
      quantitative and ultrastructural study.
AB  - Ultrastructural data on the third abdominal ganglion of the crayfish was
      heretofore only available for adult individuals. The fine structure of neurons in
      the adult that are involved in the escape response has been described in detail,
      but no similar data existed for the postnatal individual. An increase in the
      number of neurons in the third abdominal ganglion during postnatal stages had
      been reported, which suggested that several changes in the features of neurons
      may occur. Here we describe the general anatomy and ultrastructure of the early
      postnatal third abdominal ganglion, with emphasis on neurons, and we compare
      their characteristics to those of the adult. Abdominal ganglia of 56 crayfish of
      0, 8, 10, 18, 25, 50, 110, and 150 postnatal days were processed under cacodylate
      buffered aldehyde fixatives, osmicated, embedded in plastic, sectioned, and
      examined by light and electron microscopy. The anatomy of postnatal ganglia is
      homologous to the anatomy of the adult ganglia except that the perineurium is not
      developed in postnatals. The area of neurons within the postnatal ganglion shows
      no stratification, but neurons are grouped in nuclei according to their size.
      Neurons constitute a homogeneous population in different stages of maturity, as
      revealed particularly by the ultrastructure of the nucleolus. Postnatal
      development is evident in the perineurium, which may provide structural support
      to the ganglion.

PMID- 18627809
TI  - Morphological organization of the male brood pouch epithelium of Syngnathus
      abaster Risso (Teleostea, Syngnathidae) before, during, and after egg incubation.
AB  - The morphological organization of the male brood pouch epithelium of Syngnathus
      abaster, before, during, and after the breeding period, was observed by light and
      electron microscopy. Before gestation, the epithelium of the pouch wall was
      compact and consisted of three kinds of cells: typical epithelial cells (pavement
      cells), mitochondria-rich cells (MR cells), and, presumably, differentiating MR
      cells. In this stage, very few capillaries were observed beneath the epithelium.
      During egg incubation, the capillaries increased in number and size, large
      intercellular spaces formed among epithelial cells at their basal sides, MR cells
      were abundant, and differentiating MR cells were only occasionally observed.
      After incubation, MR cells degenerated by necrosis and apoptosis. The
      intercellular spaces between the epithelial cells disappeared and the number and
      size of the capillaries beneath the epithelium decreased. The presence of MR
      cells during gestation and their degeneration after incubation suggest that these
      cells play a pivotal role in the physiological functions of the brood pouch. The
      similar cytological characteristics of syngnathid pouch MR cells and chloride
      cells of the teleostean gills suggests that the Syngnathidae brood pouch is
      involved in osmoregulation of the fluid surrounding the developing embryos.

PMID- 18627810
TI  - Structure and development of the telotrophic ovariole in ensign scale insects
      (Hemiptera, Coccomorpha: Ortheziidae).
AB  - The paired ovaries of young larva of the 3rd instar of Orthezia urticae are
      filled with numerous germ cell clusters that can be regarded as ovariole anlagen.
      Germ cells (cystocytes) belonging to one cluster form a rosette, in the centre of
      which a polyfusome occurs. Staining with rhodamine-phalloidin has revealed that
      polyfusomes contain numerous microfilaments. The number of cystocytes per cluster
      is not stable and varies considerably. The ovaries of older larva become
      elongated with numerous young ovarioles protruding into the body cavity. The
      ovarioles are not subdivided into the tropharium and vitellarium. In this stage
      germ cells differentiate into oocytes and trophocytes (nurse cells). The ovaries
      of adult females are composed of about 20 (Newsteadia floccosa) or 30 (O.
      urticae) ovarioles. Their trophic chambers contain trophocytes and arrested
      oocytes. In the vitellarium, at the given moment, only one oocyte develops. It
      has been observed that after maturation of the first egg the arrested oocytes may
      develop.

PMID- 18627811
TI  - Cell junctions in the endocrine dorsal body cells of Helisoma duryi (Mollusca:
      Pulmonata): an in vitro study.
AB  - The endocrine dorsal bodies of gastropod molluscs regulate reproduction and are
      closely associated with the central nervous system. Previous studies on Helisoma
      duryi have shown that the dorsal body cells of reproducing snails contain more
      gap junctions than those of non-reproducing virgin snails. More dorsal body cells
      were isolated from virgin snails than reproducing snails in Ca(2+) and Mg(2+)
      free experimental saline. The isolated spherical cells attached to the culture
      dish, spread and formed filopodium-like processes within a few hours in culture
      medium containing Ca(2+) and Mg(2+). Many isolated cells reaggregated after 4-6 h
      in culture forming septate junction-like and gap junction-like cell contacts, as
      revealed by thin section and freeze-fracture studies. Following 10 min incubation
      in carboxyfluorescein diacetate the isolated cells fluoresced and, after
      aggregation, these cells transferred fluorescent dye to unlabelled cells. Cell
      aggregation was inhibited by cytochalasin D. Staining by NBD-phallacidin revealed
      the presence of actin in the filopodium-like processes of spread cells and in the
      perinuclear cytoplasm. It is likely that the septate junction-like contacts
      provide sites of cell attachment between aggregating cells; gap junctions are
      involved in intercellular communication, and actin is required in this process.

PMID- 18627812
TI  - Ultrastructural changes of the anterior and posterior sternal integument of the
      terrestrial isopod Porcellio scaber Latr. (Crustacea) during the moult cycle.
AB  - The ultrastructure of the anterior (ASE) and posterior sternal epithelium (PSE)
      was investigated during the biphasic moult cycle. During early premoult the
      sternal epithelial cells increase in size, accumulate huge amounts of glycogen,
      and increase the abundance of cellular organelles. CaCO(3) deposit formation
      begins before the secretion of the epicuticle in the anterior sternal integument
      and continues through the secretion of the first exocuticular layers. The
      deposition of cuticle is delayed in the ASE until the CaCO(3) deposit is fully
      resorbed between the anterior and posterior moult. The development of the
      interstitial network (IN), which enormously increases the basolateral compartment
      of the plasma membrane, starts at the beginning of the exocuticle deposition.
      During CaCO(3) deposit formation and resorption the volume fraction of the
      mitochondria is much larger in the ASE than in the PSE, although the cuticle is
      secreted faster in the posterior integument. The results suggest that the
      exocuticular and epicuticular layers are permeable to calcium and probably also
      carbonate ions; that the IN is required during late premoult, when CaCO(3)
      deposition is accelerated, but not during early CaCO(3) deposition; and that
      active mechanisms contribute to transepithelial ion transport during CaCO(3)
      deposit formation and resorption.

PMID- 18627813
TI  - Sponge cell culture: a comparative evaluation of adhesion to a native tissue
      extract and other culture substrates.
AB  - Hexactinellids are deep water sponges that possess syncytial rather than cellular
      tissues. In order to investigate the syncytial character of the tissue of these
      unusual sponges, primary cultures were developed using a substrate of acellular
      tissue extract (ATE) that promotes the adhesion and spreading of sponge tissues.
      Primary cultures of the hexactinellid sponge Rhabdocalyptus dawsoni, grown on
      this substrate, form thinly spread, multinucleate, confluent tissue masses which
      exhibit active cytoplasmic streaming. Sponge tissue adhered equally well to
      commercial substrates of concanavalin A and poly-l-lysine, but did not adhere to
      chicken collagen. Acellular tissue extracts prepared from demosponges, which are
      known to be cellular, also promoted adhesion and spreading of cells from those
      sponges. Scanning electron microscopy showed adherent Rhabdocalyptus tissue to
      have an uninterrupted, smooth membrane covering the entire culture, unlike
      primary cultures of the cellular demosponge, Haliclona sp., which consisted of
      numerous individual cells. Tissue from freshly collected sponges adhered
      preferentially to ATE from a conspecific. However, after continued wounding,
      tissue adhered indescriminately to any substrate. The tissue extract congealed if
      added to sea water or 10 mM CaCl(2), forming a white, cloudy solid, which could
      be fixed and sectioned for transmission electron microscopy. Thin sections of the
      congealed extract showed it to contain membranes but no visible collagen fibrils.

PMID- 18627814
TI  - Seasonal changes of the Leydig cells of viscacha (Lagostomus maximus maximus). A
      light and electron microscopy study.
AB  - The Leydig cells of viscacha (seasonal rodent) show cytoplasmic hypertrophy and
      regional distribution during the breeding period (summer-autumn). The dominant
      organelles are smooth endoplasmic reticulum (SER) and mitochondria. A moderately
      well-developed Golgi, abundant lipid inclusions, dense bodies like lysosomes in
      different stages, and centrioles are observed. Extensive or focal desmosome and
      gap-like junctions between neighbouring Leydig cells are present. These cells
      exhibit an evident hypotrophy and an increase in the number of dense bodies
      during the gonadal regression in winter (July and August). Cells in different
      stages of involution are observed in this period. Their nuclei are irregular and
      heterochromatic. The cytoplasm contains few mitochondria. The vesicular SER is
      scarse. Irregular and large intercellular spaces with microvilli and amorphous
      material are present. The junctional complexes are absent. The nuclear and
      cytoplasmic volume and development of SER and mitochondria increase during the
      recovery period (spring). The lipid inclusions decrease. Dilatations of the
      intercellular space with microvilli and limited by focal desmosome-like junctions
      are observed. In conclusion, the Leydig cells of Lagostomus maximus maximus show
      deep changes alongside the reproductive cycle. The photoperiod variations,
      through pineal hypothalamus pituitary axis and the hormone melatonin, are
      probably responsible for them. Moreover, the fall of serum and tubular
      testosterone would be one of the factors responsible for gonadal regression.

PMID- 18627815
TI  - Intracellular distribution of iron (and associated elements) in various cell
      types of larvae and juveniles of the sea lamprey (Petromyzon marinus).
AB  - The intracellular distribution of iron and other elements was examined in various
      cell types in larvae and juveniles of the sea lamprey (Petromyzon marinus) using
      transmission electron microscopy and energy dispersive x-ray microanalysis. The
      objective was to establish whether there are cell-type specific relationships
      between iron and other elements in the iron-rich organs and tissues (adipose
      tissue, opisthonephric kidneys, dorsal integument, fat column, liver, and
      posterior intestine) of these two life cycle periods. Iron was localized within
      either dense bodies (presumptive lysosomes, siderosomes) or in the cytoplasmic
      matrix of many cell types where it was viewed as haemosiderin/ferritin and
      ferritin, respectively. Presumptive lysosomes of adipocytes of the nephric folds,
      dorsal integument, and fat column possessed iron and sulphur and this elemental
      association was also prevalent in the epithelia of the larval proximal tubules
      and in the posterior intestine and epidermis of both life periods. Macrophages of
      the larval haemopoietic tissue (posterior intestine) and of the juvenile
      opisthonephros, which were described as melanomacrophages because of their
      granules, possessed iron, sulphur, and calcium. This elemental association was
      also noted in the presumptive lysosomes of the iron-loaded hepatocytes of the
      juvenile liver while no elements could be detected in these cells in the larval
      organ. The variations and similarities in elemental associations between the cell
      types in each life period and at different life periods is discussed in the
      context of specific cell functions related to the prevention of iron toxicity.
      These functions are sequestration of iron and storage as the less toxic
      haemosiderin (larval adipocytes, macrophages, juvenile hepatocytes) or as part of
      a process of elimination of excesses of this metal (posterior intestine, dorsal
      epidermal cells). Due to its unique ability to deal with copious amounts of iron
      at all periods of the life cycle, the lamprey serves as an important model for
      studies of iron loading in vertebrates.

PMID- 18627816
TI  - Germ cells cluster organization in polytrophic ovaries of neuroptera.
AB  - Histological and ultrastructural analysis of polytrophic ovary structure in
      Neuroptera revealed an unusual organization of their germ cell clusters. In all
      species under study (representing 5 families), clusters with variable and unfixed
      numbers of cystocytes are formed. Moreover, spatial organization of cystocyte
      connections within the cluster is linear rather than typically branched; only a
      few branching sites being observed. The oocyte is located in the central, always
      linear, part of the cluster and therefore is directly connected via intercellular
      bridges with only two nurse cells. It is postulated here that the linear
      character of germ cell clusters in Neuroptera may result from asynchrony of
      cystocyte divisions. Mechanisms of germ cell cluster formation and
      differentiation are discussed.

PMID- 18627817
TI  - The yolk sac in late embryonic development of the stick insect Carausius morosus
      (Br.).
AB  - Differentiation of the yolk sac was examined ultrastructurally and cytochemically
      in late embryonic development of the stick insect Carausius morosus. During
      migration along the yolk sac, endodermal cells form a discontinuous cell
      epithelium, leaving wide intercellular channels between neighbouring cell
      clusters. Within the same cell cluster, cells are all joined by septate
      junctions. In the proximity of the proctodeum region, intercellular channels are
      filled with numerous cell debris which are shown to derive from vitellophages
      undergoing cell lysis. Yolk sacs resolved by gel electrophoresis are shown to
      release a number of vitellin polypeptides into the culture medium. These are
      equivalent in molecular weight to those present in the vitellophage yolk granules
      This observation is consistent with the evidence that the basement lamina may act
      as a course physical filter, retaining particles larger than colloidal thorium
      dioxide and allowing free percolation of peroxidase. Differentiating endodermal
      cells form a microvillar striated border along the apical plasma membrane. A
      number of vesicular criptae were frequently seen in these differentiating
      endodermal cells. Electron dense granules released by endodermal cells are
      suggested to play a role in vitellophage lysis and vitellin release from the
      enclosed yolk granules.

PMID- 18627818
TI  - An electron microscopic study of the endocrine dorsal bodies in reproductively
      active and inactive Siphonaria pectinata (Pulmonata: Mollusca).
AB  - The fine structure of the dorsal bodies of the pulmonate limpet Siphonaria
      pectinata is described in the context of female reproduction involving egg
      production. In reproductively-active (egg-laying) animals, the ciliated dorsal
      body cells are filled with lipid droplets and mitochondria. Gap junctions are
      commonly seen between the cells. The Golgi complexes and the smooth endoplasmic
      reticulum constitute the other prominent cell organelles. In reproductively
      inactive (non-egg-laying) animals, there is a significant reduction in the number
      of lipid droplets and evidence of reduced synthetic activity in the dorsal
      bodies. About 12 dorsal body cells are present immediately underneath the
      perineurium of each cerebral ganglion of the central nervous system. These
      internal cells are structurally similar to those outside the central nervous
      system. Cell processes of some of these cells exit the central nervous system at
      a minimum of three locations on each side and they come in close proximity to the
      dorsal body cells outside the cerebral ganglia. Like the external cells, the
      internal cells also communicate via gap junctions and exhibit structural
      differences according to whether or not the animals are reproductively active.
      The dorsal body cells, inside and outside the central nervous system, appear to
      be innervated by neurosecretory axons suggesting neuronal control of dorsal body
      activity.

PMID- 18627819
TI  - Spermatocytes of the caddisfly Potamophylax rotundipennis (Trichoptera, Insecta):
      a fine structure study with emphasis on synaptonemal complex plates associated
      with chromatin.
AB  - Electron microscopy of ultrathin sections was used to study the restructuring of
      primary spermatocytes in a caddisfly, Potamophylax rotundipennis (Limnephilidae).
      Spindle structure was also examined using light microscopy of dividing
      spermatocytes lysed in a microtubule-stabilizing buffer. The bulk of pachytene
      spermatocytes was usual in that the nuclei contained tripartite synaptonemal
      complexes (SCs). The SCs were attached end-on to the inner face of the nuclear
      envelope and loosely surrounded by electron-dense chromatin. Cells of this type
      gave rise to late prophase I spermatocytes, where SCs were missing and chromatin
      condensation was advanced. By metaphase I, a conventional bipolar spindle
      apparatus assembled, bivalents were aligned at the spindle equator, and membrane
      sheets were scattered throughout the spindle matrix. Prominent interzone spindles
      were typical of telophase spermatocytes. However, a subset of prophase I
      spermatocytes possessed unusual forms of SCs. The analysis of short series of
      ultrathin sections through the nuclei revealed plates composed of synaptonemal
      complex material. These elements will be referred to as 'SC plates'. Within the
      SC plates, the tripartite organization typical of regular SCs was preserved. The
      chromatin surrounding the SC plates was highly condensed. The SC plates ended
      abruptly within the nuclear lumen and did not reach the nuclear envelope.
      Finally, branching of SC plates was common. In light of the bizarre organization
      of SC material and its relation to the chromatin, and because spermatocytes with
      SC plates do not readily fit into the regular development of male germ cells in
      the caddisfly, we venture the suggestion that the SC plates are not physiological
      intermediates of SC disassembly. The affected cells most probably fail to
      complete meiosis.

PMID- 18627820
TI  - The vitellin-processing protease of Blattella germanica is derived from a pro
      protease of maternal origin.
AB  - Proteolytic processing of vitellin in Blattella germanica embryos is accomplished
      by activation of a yolk-borne cysteine protease (Mr 29 000) derived from a pro
      protease precursor of Mr 40 000 (Liu et al., 1997). In the present study, fat
      body, ovaries and embryos of different developmental stages were examined immuno
      cytochemically with purified murine anti-proprotease antibodies (Liu, 1995) to
      determine the intracellular location of the pro-protease. Proenzyme was detected
      in discrete secretory granules of the fat body and in large lysosome-like
      vesicles of both the follicle cell cytoplasm and the cortical ooplasm of
      previtellogenic ovarian follicles. In vitellogenic oocytes, coated pits and
      vesicles are scantily labelled for proprotease and no clear gold pattern could be
      discerned over the yolk granules. During embryonic development, pro-protease is
      associated with some, but not all, yolk granules. In newlyovulated eggs (day 0),
      pro-protease is either distributed over the entire granule or confined to some
      internal vesicles. As development proceeds, it becomes associated with almost
      every yolk granule and restricted to the superficial layer. By day 6, pro
      protease is evident over all yolk granules but the intensity of reaction has
      greatly diminished, due probably to conversion of the pro-protease to the mature
      enzyme. Yolk granules are flanked along their margin by vesicles that are stained
      after zinc-osmium fixation. This observation suggests that the pro-protease may
      be transferred between yolk granules via vesicular shuttling. B. germanica
      embryos of different developmental stages were also exposed to [(3)H]-DAMP. Data
      show that autoradiographic grains are not evenly distributed among closely
      adjacent yolk granules within vitellophagic cells, a result consistent with the
      known slight temporal asynchrony of the acidification event.

PMID- 18627821
TI  - Structure and function of the ovarian cavity and oviduct and composition of the
      ovarian fluid in the bleak, Alburnus alburnus (Teleostei, Cyprinidae).
AB  - The ovarian cavity and the oviduct of Alburnus alburnus were investigated by
      histological, fine structural and (enzyme-) histochemical methods, and the
      ovarian fluid was analysed. Within the ovary there exists a system of
      communicating cavities, the ovarian cavity, which caudally continues with the
      oviduct. The ovarian cavity is bordered by an epithelium which is secretory
      active and covered with microvilli. It is involved in the formation of an ionic
      gradient in the ovarian fluid, in the secretion of glucose, proteins and enzymes
      (acid phosphatase, protease, beta d-glucuronidase) and in the synthesis of
      glucuronide steroids which is established by analysis data of the ovarian fluid.
      It has also auto- and heterophagocytotic activity. The oviduct epithelium
      consists mainly of ciliated cells which direct the eggs through the oviduct.
      Between the ciliated cells, clusters of microvilli cells are located which are
      similar to the epithelium of the ovarian cavity.

PMID- 18627822
TI  - Presence of sialic acid in prothoracic glands of Galleria mellonella
      (Lepidoptera).
AB  - The presence of sialic acid (SA) in prothoracic glands (PGs) of Galleria
      mellonella was determined by the methods of electron microscopy (EM),
      histochemistry, spectrophotometry (SP) and electronic ionization (EI)-mass
      spectroscopy. Histochemical observations were carried out by the cationic dye
      ruthenium red (RR), staining with and without neuraminidase digestion in the
      larval stage. Neuraminidase-sensitive SA was demonstrated by the decrease in the
      amount of RR-binding following neuraminidase digestion. The total amount of SA
      was found to be 0.09016 mg g(-1) in dry tissue by spectrophotometric
      determination. EI-mass spectroscopy results confirmed the EM and SP observations.
      The fragmentation scheme derived from EI-mass analysis exhibited the presence of
      the lactonized form of Neu5Gc7, 9Ac(2). On the basis of the various pieces of
      evidence described above, it was firmly concluded that Neu5Gc7, 9Ac(2) molecules
      were present in PGs of G. mellonella.

PMID- 18627823
TI  - Plasma membrane specializations in resting, stimulated and phagocytosing
      arthropod (Limulus polyphemus, Gromphadorhina portentosa and Blattella germanica)
      immunocytes: structural and functional analogies with those of vertebrate
      macrophages and neutrophils.
AB  - Using indirect immunofluorescence and scanning electron microscope techniques, we
      have shown that the plasma membrane specializations, such as pseudopods,
      filopods, lamellipods, and zeiotic blebs occur in activated and/or phagocytosing
      arthropod (Limulus polyphemus, Gromphadorhina portentosa, and Blattella
      germanica) immunocytes (hemocytes), as they do in challenged vertebrate
      neutrophils and macrophages. All four specializations may also be caused by some
      of the chemicals in the preparative media, which suggests that arthropod
      immunocytes, like the vertebrate neutrophils and macrophages, have evolved as
      highly reactive cells that are sensitive to chemical and/or biological foreign
      agonists/antigens. These attributes are necessary for the effectiveness of a
      cellular defense mechanism. The plasma membrane specializations perform the same
      functions in arthropod immunocytes as reported for those of vertebrates. For
      example, pseudopods and lamellipods are needed for spreading and locomotion and
      filopodia for cell adhesion and crawling. Because they are formed as a result of
      similar reactions to foreign antigens, as in vertebrate cells, it is suggested
      that similar terminologies be consistently used for them in arthropods.

PMID- 18627824
TI  - Fine structural correlates of sensitivity in the eyes of the ctenid spider,
      Cupiennius salei Keys.
AB  - We studied fine structural correlates of sensitivity in the principal and
      secondary eyes of the nocturnal hunting spider Cupiennius salei. In night-adapted
      eyes the four rhabdomeres of the principal eye photoreceptors are 58 microm long
      and occupy together 234 microm(2) in cross-section (average), whereas the two
      rhabdomeres of the secondary eye photoreceptors are about 49 microm long and
      measure 135-183 microm(2) in cross-section (average). The rhabdoms
      (photosensitive structures) consist of tightly packed microvilli (diameter 0.1
      microm, maximum length 3.5 microm) and occupy up to 63% of the cross-sectional
      area of the retina. When calculating the amount of light the eyes of Cupiennius
      are able to capture according to their morphological characteristics, the values
      for sensitivity S(see Land, 1981, 1985) are between 78 and 109 microm(2).
      Cupiennius is more sensitive than any other hunting spider examined except
      Dinopis whose posterior median eyes are the most sensitive ones of all
      terrestrial arthropod eyes studied. In day-adapted eyes the rhabdomeral
      microvilli are almost completely degraded. The remaining microvillar surface
      amounts to only about one-tenth compared with the night-adapted state. Efferent
      synaptoid terminals have been found to contact the photoreceptors in all eyes of
      C. salei. The present fine structural data are compared to previous
      electrophysiological research and underline the significance of vision in
      Cupiennius.

PMID- 18627825
TI  - Rodlet cells in the epidermis of fish exposed to stressors.
AB  - Rodlet cells (RC) were detected in the epidermis of carp (Cyprinus carpio) and
      trout (Oncorhynchus mykiss) exposed to stressors (e.g. acid water, heavy metals,
      thermal elevation, polluted water of the Rhine river, water loaded with organic
      manure, and distilled water), as well as after wounding. These cells were not
      found in the epidermis of fish kept under control conditions, thus suggesting
      that the appearance of RC in the epidermis is stressor-related. Immature RC,
      resembling mucous cells, were found in deeper epidermal zones while mature RC
      were found close to and at the skin surface. The latter contained several rodlets
      embraced within a capsule-like structure composed of filaments. At the skin
      surface, RC opened the filamentous capsule at the cell apex and a cytoplasmic
      tuft, containing the rodlets, protruded outwards into the surrounding water.
      Structures which appeared to be free rodlets were also observed in the water,
      near the ridges of the pavement cells. Cytochemical and immunocytochemical study
      revealed that the rodlets contain alkaline phosphatase at their periphery and
      peroxidase activity at their cores. These enzymes have been previously reported
      in mucous cells of stressed fish. All together, the location of RC, their
      structure, cytochemistry and direction of migration suggest that these cells form
      part of the non-specific defence mechanism of the skin, and possibly other
      epithelial tissues.

PMID- 18627826
TI  - Ultrastructural study of chloride cells in the trunk epithelium of larval
      herring, Clupea harengus.
AB  - Mitochondria-rich cells of the mid-trunk region of herring larvae, as revealed by
      DASPMI staining under fluorescent microscopy, were identified as chloride cells.
      The chloride cells were generally solitary, and seldom made direct contact with
      each other. The shape of the cells varied with position on the body wall, those
      in dorsal locations being more compressed in the apical/basal direction. The
      structure of the chloride cells was similar to that described for other teleost
      species but there were considerable differences between ventral and dorsal cells.
      The volume fraction of mitochondria and diameters of mitochondria, cristae, and
      terminal expansions of cristae were all smaller in the dorsal cells. Tubular
      network density was relatively constant whilst smooth endoplasmic reticulum (SER)
      density and vesicotubular density, of the subapical cytoplasm, exhibited a high
      variation which did not correlate with the presence or absence of accessory
      cells. The apical membranes of both cell types were flush with the epithelium and
      did not form a crypt, even when interdigitating processes of an accessory cell
      were present. Accessory cell interdigitations were generally observed for the
      apical membrane of ventral cells but were seldom observed in the more dorsal
      cells of the segmental bands. The ultrastructural evidence suggests that the
      ventral cells are functional in ion pumping whereas the majority of chloride
      cells of the dorsal segmental bands were probably not functional in ion pumping.

PMID- 18627827
TI  - Peritrophic membrane structure and secretion in European corn borer larvae
      (Ostrinia nubilalis).
AB  - Peritrophic membrane (PM) secretion and formation occur primarily in the anterior
      region of the mesenteron in the European corn borer (Ostrinia nubilalis) as
      determined by light and electron microscopy. Nascent PM first became visible as
      fibrous linear chitin-containing structures stained with gold-labeled wheat germ
      agglutinin between and at the tips of the microvilli. No formed PM was visible at
      the foregut-midgut junction, but a thin single PM appeared first in the lumen
      between the stomodeal valves and the midgut epithelium. Just posterior to the
      stomodeal valves, multiple PMs were observed that became progressively thicker
      and more numerous in the mid and posterior regions of the mesenteron. The PM
      consists of an orthogonal chitin meshwork with openings slightly larger than the
      diameters of the microvilli. As it delaminates from the microvilli, the meshwork
      becomes embedded in proteinaceous matrix that greatly reduces the pore size of
      the PM.

PMID- 18627828
TI  - Salinity-induced changes in the fine structure of the gills of the
      semiterrestrial estuarian crab, Uca uruguayensis (Nobili, 1901) (Decapoda,
      Ocypodidae).
AB  - The posterior gills of Uca uruguayensis are mostly lined with a thick tissue
      which presents the characteristics of a typical salt-transporting epithelium.
      Electron microscope analysis of gill tissue from crabs acclimated to both low
      (2.5 per thousand) and high (44 per thousand) salinity showed significant
      development of the basolateral membrane interdigitations with numerous
      mitochondria and conspicuous apical membrane infoldings. In high-salinity
      acclimated crabs, the basolateral interdigitations extended to the apical
      membrane. Under these conditions, apical infoldings were expanded laterally
      (forming wide subcuticular spaces), while the apical infoldings of low-salinity
      adapted animals appeared as regular leaflets. Septate desmosomes were also much
      more developed in low-salinity exposed animals than in those kept under high
      salinity conditions. These morphological observations were analyzed for
      correlation with the currently-accepted ion hyporegulation model for crustaceans,
      which is mainly based on transcellular sodium flow. In this study, we propose an
      ion hyporegulation model involving apical paracellular sodium flux.

PMID- 18627829
TI  - An immunocytochemical and ultrastructural study of the larval anterior intestine
      of the frog Rana temporaria, with especial reference to endocrine cells.
AB  - Endocrine cells of the larval intestine of Rana temporaria tadpoles have been
      identified by argyrophilic, immunocytochemical and electron-microscopical
      techniques. Scarce endocrine cells have been found in both the short non
      absorptive zone immediately following the stomach, and in the rest of the
      anterior intestine. Endocrine cells are frequently seen to extend a cytoplasmic
      process towards the lumen. Immunoreactivity for serotonin, somatostatin, bombesin
      and cholecystokinin-8 has been detected. According to the ultrastructural traits
      of the endocrine granules, three larval intestinal endocrine populations have
      been differentiated.

PMID- 18627830
TI  - Perineuronal glial system in the cerebral ganglion of active and hibernating
      Helix aspersa.
AB  - The electron microscopical changes in the glial lacunar network that surrounds
      the large neurons of meso- and metacerebrum of land snail cerebral ganglia were
      considered, in order to get an insight into the functional role of this peculiar
      structure in invertebrates. Compared with snails during the active period, in the
      hibernating animals the extension of glial processes was reduced and the glial
      processes appeared more regular and stacked around neurons. Moreover, they did
      not form deep, long interdigitations with neuronal infoldings as during the
      active period. In particular, data on the ultracytochemical detection of alkaline
      phosphatase and Ca(2+)/Mg(2+)-ATPase enzyme activities, point to a correlation
      between the extension of the glial system and its function in the regulation of
      the extracellular environment. In fact, in hibernating snails, lower reactivity
      was found on the glial membranes, including those of the trophospongium.

PMID- 18627831
TI  - An ultrastructural investigation of Hrabeiella Pizl & Chalupsky, 1984 (Annelida).
      II. The spermatozoon.
AB  - The mature spermatozoa of the terrestrial non-clitellate annelid Hrabeiella
      periglandulata Pizl & Chalupsky, 1984 s.l. were examined using light and electron
      microscopy. They are about 150 mum long, filiform and extremely slender (maximum
      diameter, 450-475 nm). The acrosome is very elongate (about 25 mum), tapering and
      conical. Its transverse section is circular apically but shows an evident six
      rayed symmetry in its basal region. The nucleus appears convex at both ends;
      apically, it extends laterally into the acrosome, and basally, it plugs into the
      centriolar region. The nucleus is about 23 mum long and has a rounded, tri- to
      pentalobed, slightly helical profile. The midpiece contains one elongate, free
      (paraxonemal) mitochondrion, 27 accessory tubules, which are slightly larger and
      more opaque than the axonemal microtubules; and seven electron-dense, non
      membrane-bounded rods distributed around the axoneme. The flagellum tapers
      rapidly posteriorly. None of the observed similarities to the sperm (introsperm)
      of questids, protodrilids or other polychaetes seems to represent an immediate
      synapomorphy. None of the spermatozoal autapomorphies of the Euclitellata is
      shared by Hrabeiella.

PMID- 18627832
TI  - Sperm morphology of salamandrids (Amphibia, Urodela): implications for phylogeny
      and fertilization biology.
AB  - Mature spermatozoa belonging to four salamander species, Salamandrina
      terdigitata, Triturus alpestris, Triturus carnifex and Triturus vulgaris, have
      been investigated by electron microscopy. The sperm ultrastructure of these
      species was compared with that of previously examined urodeles (36 species and 20
      genera) and with that of anurans and caecilians. Many phylogenetic considerations
      may be inferred as a consequence of comparative spermatology. Urodela appears to
      be a monophyletic order characterized by three sperm synapomorphies: the
      acrosomal barb, nuclear ridge and marginal filament. Cryptobranchoidea are
      confirmed to form a monophyletic suborder having two synapomorphic characters:
      absence of mitochondria in the tail, and cylindrical shape of the tail axial rod.
      Within the family Salamandridae, sperm morphology confirms the phylogenetic
      distance between Salamandrina and Triturus, as already pointed out on the basis
      of molecular and morphological characters. The very complex ultrastructure of
      spermatozoa confirms a previous opinion that internal fertilization is the
      ancestral condition of the Amphibia.

PMID- 18627833
TI  - Maturation of mosquito spermatozoa during their transit throughout the male and
      female reproductive systems.
AB  - The testes, seminal vesicles and spermathecae of 22 species of mosquitoes
      belonging to the genera Aedes, Anopheles, Culex, Mansonia and Toxorhynchites are
      investigated under the electron microscope. Modifications of the acrosome and
      sperm wall occur during the transit of the spermatozoon from the lower region of
      the testes to the spermathecae throughout the seminal vesicles. The origin and
      fate of the cell coat and the possible roles of somatic cell layers both in the
      testes and the seminal vesicles are discussed.

PMID- 18627834
TI  - Structure and development of first-generation teeth in the cichlid Hemichromis
      bimaculatus (Teleostei, Cichlidae).
AB  - In order to build a reference system to assess results of ongoing in vitro
      experiments on the study of epithelial-mesenchymal interactions during
      odontogenesis in actinopterygians, we have chosen to study the first-generation
      teeth of the cichlid Hemichromis bimaculatus from initiation until attachment
      both at the light and transmission electron microscopical level. Although their
      development follows the general pattern of teleost tooth formation, first
      generation teeth show peculiarities compared with later tooth generations,
      including their size, bare emergence from the epithelium, absence of dentinal
      tubules and of nerves and capillaries in the pulp cavity, and organization of the
      outer dental epithelium. Four developmental stages (a to d) prior to attachment
      (stage e) have been distinguished. The oral epithelium invaginates into the
      underlying mesenchyme (stage a) and is later folded to form a bell-shaped dental
      organ (stage b) without any primordial thickening, or any other morphological
      indication of imminent invagination. Then, the collagenous enameloid matrix is
      laid down, most probably by the odontoblasts (early stage c), soon followed by
      predentine deposition and the beginning of enameloid mineralization (late stage
      c). With ongoing dentinogenesis, the enameloid matrix matures (stage d), i.e. the
      organic constituents are removed and the matrix further mineralizes. Finally
      (stage e), an annular collar of attachment bone is deposited to fix the tooth
      onto the underlying bone.

PMID- 18627835
TI  - Ultrastructural changes in corpora allata during a cycle of juvenile hormone
      biosynthesis in embryos of the viviparous cockroach, Diploptera punctata.
AB  - We have observed changes with time in the fine structure of corpora allata (CA)
      during a known cycle of increasing and decreasing juvenile hormone (JH) synthesis
      in late embryos of Diploptera punctata. A previous report showed that rates of JH
      release were relatively low in 28-day-old embryos, but CA activity subsequently
      rose linearly to a peak on about day 42, and thereafter steadily declined to a
      low level on day 64 just before birth (Holbrook et al., 1997). We now show that,
      regardless of rate of JH synthesis, CA cells are large and replete with
      organelles which nevertheless exhibit variable morphology in embryos of different
      age. Highly active CA cells on day 40 contain abundant ring-form mitochondria,
      whereas CA cells of low activity on days 28 and 64 contain mitochondria that are
      rod-shaped or globular. Mitochondrial cristae were scarce and indistinct on day
      28 but numerous and well developed on day 64. Endoplasmic reticula (ER) are rare
      on day 28 and appear in increasing numbers when CA activity rises. On day 40, ER
      are abundant and often exhibit a whorl-like appearance which is not observed on
      day 28. After day 44, when biosynthetic activity is declining, whorls of ER
      gradually decrease in number and are ultimately replaced by vesicular smooth ER
      on day 64. Neurosecretions are found only after day 38, by which time rates of JH
      synthesis have increased substantially from those of day 28. Except for
      membranous autophagic vacuoles, which are frequently found when ER whorls
      disintegrate as rates of JH synthesis decline toward birth, most autophagic
      vesicles such as multivesicular vesicles and dense bodies occur only sporadically
      among CA cells at all examined ages. We conclude that synchronous autophagy of
      exhausted organelles, which results in atrophy of CA cells and long-term arrest
      of JH synthesis in adult females of D. punctata, does not occur in embryos. The
      slow cyclic change in rate of JH synthesis in embryonic CA is most likely due to
      asynchronous autophagic activity and to alterations in certain unique features of
      intracellular organelles.

PMID- 18627836
TI  - Functional morphology of a double-walled multiporous olfactory sensillum: the
      sensillum coeloconicum of Bombyx mori (Insecta, Lepidoptera).
AB  - The fine structure of coeloconic sensilla of Bombyx mori was studied in cryofixed
      specimens. These sensilla belong to the category of double-walled wall-pore
      sensilla. The pegs are approximately 10 microm long, located in pits on the
      dorsal side of the antennal branches, and longitudinally grooved in their distal
      half (grooved surface approximately 30 microm(2)). The central lumen contains the
      outer dendritic segments of usually five receptor cells, and is surrounded by up
      to 15 partially fused cuticular fingers. The peripheral lumina of these cuticular
      fingers are filled with material resembling wax-canal filaments. Radial spoke
      channels (approximately 600 per peg), each 10-20 nm wide, connect the central
      lumen with the longitudinal groove channels. Groove and spoke channels are
      assumed to mediate the transport of odorant molecules from the outer epicuticular
      surface layers to the sensory dendrites. Thus the double-walled wall-pore
      sensilla represent a bauplan essentially different from single-walled wall-pore
      sensilla; the reason, however, why the two types are found together throughout
      the insect orders remains enigmatic. Other peculiar features of the coeloconic
      sensilla of the silkmoth are invaginations of the outer dendritic segments and
      direct contacts between the receptor cell somata. The latter may be the
      structural correlate to electrophysiological observations indicative of
      peripheral interaction between the receptor neurons. All three auxiliary cells
      have elaborately folded apical plasma membranes studded with portasomes and
      associated with an abundance of mitochondria; basally they often contact tracheal
      branches. As compared to the auxiliary cells of the single-walled olfactory
      sensilla of the same species, all the mentioned features are much more prominent
      and hint to a higher ion pumping activity at the border to the sensillum-lymph
      cavities.

PMID- 18627837
TI  - Fine structural survey of old cuticle degradation during pre-ecdysis in two
      European Atlantic crabs.
AB  - Light and transmission electron microscopy were used to monitor changes due to
      the degradation of the old exoskeleton and related events in the sclerites,
      articular membranes, and gills of two decapod crustaceans (Carcinus maenas and
      Macropipus puber) during pre-ecdysis. In both sclerites and articular membranes,
      degradation follows a similar general pattern in both crab species, while the
      gill cuticle appears unaltered. In early pre-ecdysis (D(0)), the degradation of
      the old cuticle starts with the secretion of ecdysial droplets by the epidermis.
      Apolysis, occurring at stage D(1)', is re-defined as an event, not necessarily
      morphologically observable, consisting in the loss of adherence between the
      epidermis and the old cuticle during early pre-ecdysis of arthropods. At the
      stage D(1)''', the moulding of the epidermal cell surface occurs in preparation
      to the deposition of the new cuticle and causes the opening of the ecdysial
      cleft. In the principal layer of sclerites, degradation of the chitin-protein
      microfibres should precede mineral dissolution. In contrast to the other degraded
      cuticle layers, the membranous layer of sclerites and the innermost endocuticular
      lamellae of articular membranes are transformed into a digestion-resistant
      fibrous network resembling the ecdysial membrane of insects.

PMID- 18627838
TI  - Effect of wheat germ agglutinin on formation and structure of the peritrophic
      membrane in European corn borer (Ostrinia nubilalis) larvae.
AB  - European corn borer (ECB; Ostrinia nubilalis (Hubner)) larvae (third instar) fed
      0.05% w/w wheat germ agglutinin (WGA) in their diet for 72 h showed very little
      increase in body weight, whereas weight of control larvae increased nearly
      fourfold. Light and transmission electron microscopy studies showed that the
      morphology of the peritrophic membrane (PM) changed within 24 h after ECB larvae
      fed on the WGA diet. Whereas the PM in the anterior region of the midgut was a
      thin membranous structure in control larvae, the WGA-fed larvae secreted a
      multiple-layered and unorganized PM that contained embedded food particles,
      bacteria, and pieces of disintegrated microvilli. Gold-labeled WGA was localized
      specifically in the PM and microvilli. The PM of WGA-fed larvae was inundated
      with dark-staining amorphous structures that, when incubated with anti-WGA,
      showed heavy WGA localization. The antibody label indicated that most of the
      ingested WGA was found in the PM, with lesser amounts on the microvillar surface
      and the least amount within the epithelium. After 72 h, the middle portion of the
      mesenteron revealed a thin, compact PM in the control larvae, whereas the PM of
      the WGA-fed larvae was multilayered and discontinuous, which allowed plant cell
      wall fragments to penetrate into the microvilli of the epithelium. Scanning
      electron microscopy of PMs from fifth instar ECB larvae fed the WGA diet revealed
      a breakdown in the chitinous meshwork by 48 h after initiation of feeding. The
      endo-PM surface from control larvae was smooth and intact, whereas the PM of WGA
      fed larvae showed disintegration of the meshwork and a reduced proteinaceous
      matrix. This allowed bacteria and food particles to penetrate through the PM into
      the ectoperitrophic space and directly contact the microvilli. Therefore, WGA, a
      protein inhibitor of larval growth, interferes with the formation and integrity
      of the PM, which exposes the brush border to ingested material. This, in turn,
      appears to stimulate secretion of additional PM layers, the concomitant
      disintegration of the microvilli, and cessation of feeding.

PMID- 18627839
TI  - Variability in molluscan hemocytes: a flow cytometric study.
AB  - Reported variability in numbers and relative proportions of hemocytes in marine
      bivalves may be related to environmental conditions and laboratory method
      differences. An automated identification assay, flow cytometry, removes much
      laboratory bias, but its usefulness is limited because the putative cell types in
      delineated subpopulations have never been confirmed. The present study was
      designed to: (1) confirm the identity of oyster hemocyte subpopulations described
      by flow cytometry, and (2) use flow cytometry in an experimental analysis of
      potential causes of variation. Light-scatter flow cytometry consistently
      differentiated three subpopulations in oysters from two mid-Atlantic (USA) sites.
      Cell sorting and microscopy identified them as granular, small granular, and
      agranular (hyalinocytes and apparently degranulated) hemocytes. Subpopulation
      proportions estimated by microscopy and by flow cytometry were significantly
      correlated (r(2) = 0.27 to 0.50). In a 4-week laboratory experiment, neither
      temperature (12 vs. 22 degrees C) nor food (fed vs. not fed) had a statistically
      significant effect on total or differential counts, or on hemocyte viability.
      Most of the variability was attributable to individual differences and was very
      similar to that reported for vertebrates. We hypothesize that variability in
      molluscan hemocytes may be more immediately linked to individual metabolic
      condition than to ambient changes.

PMID- 18627840
TI  - Distribution of serotonin uptake and binding sites in the cnidarian Renilla
      koellikeri: an autoradiographic study.
AB  - Using [(3)H]-serotonin ([(3)H]-5-HT) as radiolabel and autoradiography, we have
      mapped the distribution of 5-HT uptake and binding sites in the sea pansy Renilla
      koellikeri in order to identify potential cellular pathways of 5-HT inactivation
      and to identify cellular substrates for the previously characterized 5-HT
      receptor involved in the modulation of peristaltic behavior. Uptake measured in
      fresh polyp tissues occurred via two processes: a high affinity (uptake(1)),
      clomipramine-sensitive process with a K(m) of 0.45 microM, and another of lower
      affinity (uptake(2)) with a Km of 11.6 microM. Autoradiograms of high affinity
      uptake sites revealed a diffuse distribution of label with higher density in the
      ectoderm and endoderm, and lower density in the mesoglea. No subsets of cells,
      including serotonergic neurons, appeared to retain label preferentially, thus
      suggesting that removal of 5-HT and its chemical conversion is a general property
      of sea pansy tissues. Under incubation conditions identical to those used in a
      previous radiobinding analysis, autoradiograms of binding sites were generated on
      sections from lightly fixed and cryosectioned polyps. In contrast to uptake
      sites, binding sites appeared as aggregations of label around neurons of the
      subectodermal, mesogleal and endodermal nerve nets. In the endoderm where the
      myoepithelia subtend peristalsis, myoepithelial cells appeared unlabeled,
      suggesting that 5-HT exerts its modulatory effect on peristalsis principally via
      neurons. Taken together, these results indicate that 5-HT is released as a
      neurohormone in the sea pansy and that it may act as a broad-range
      neuromodulator.

PMID- 18627841
TI  - The twisted collagen network of the box-fish scutes.
AB  - The present article describes the three-dimensional arrangement of collagen
      fibrils in dermal plates of different species of Ostraciidae. These dermal plates
      or 'scutes' are transformed scales, which have a polygonal shape and form a rigid
      tiling. They are natural composites, associating a fibrous network with a mineral
      deposit lying at two different levels of the scute, the 'ceiling' and the
      'floor', plus a set of similarly mineralized walls joining the two levels. The
      three-dimensional structure of the collagen network can be compared to that of
      'plywood': fibrils align parallel within superposed layers of uniform thickness,
      and their direction changes from layer to layer. In the dermal plate, two types
      of plywood have been evidenced: (1) one lying between the two mineralized plates,
      where the orientation of fibrils rotates continuously, and (2) one under the
      lower plate, with thick layers of fibrils, each showing a constant orientation,
      but abrupt angular changes are observed at the transition from one layer to the
      following one. In oblique sections, both types of plywood reveal large series of
      arced patterns, testifying to a twisted arrangement of collagen fibrils,
      analogous to the arrangement of molecules or polymers in cholesteric liquid
      crystals. The network is reinforced by some collagen fibrils running
      unidirectionally and almost normally to the lamellate structure. Moreover in the
      overall organization of the scute, these plywood systems form a set of nested
      boxes. This original architecture is compared to the arrangement of the
      collagenous network previously described in most fish scales and in other
      extracellular matrices.

PMID- 18627842
TI  - Ultrastructural and histochemical study of collagen fibres types I and III in the
      venom gland of Bothrops jararaca during secretory cycle.
AB  - Fragments of snake (Bothrops jararaca) venom gland were analysed by light and
      transmission electron microscopy in order to characterize the changes in collagen
      fibres types I and III in the intertubular gland septa during the secretory
      cycle. The snakes were sacrificed at 45 days (unmilked group), 6 h, 4 and 8 days
      after manual extraction of the venom. The fragments were fixed, processed
      according to standard histologic technique for embedding in paraffin, and stained
      with haematoxylin-eosin and Gomori's trichrome and submitted to Gomori's silver
      impregnation technique and picrosirius-polarization method. For transmission
      electron microscopy the fragments were fixed and processed for embedding in
      Spurr's medium. At the 45th day (the gland at rest), when the secretory activity
      was at a minimum, the septa were narrow and filled with densely packed collagen
      fibrils. At 6 h, the septa were enlarged and exhibited wide spaces filled with
      finely granular Alcian Blue-positive material. Until the 8th day, the septa were
      narrower and the histologic aspect resembled that of the gland at rest. The
      results demonstrated structural modifications in the glandular septa according to
      the different periods of the secretory cycle. These modifications can be
      associated with the transformation in the secretory epithelium during the venom
      synthesis cycle.

PMID- 18627843
TI  - The morphological and physiological properties of the genetic tumours from a
      Nicotiana interspecific hybrid.
AB  - Many plant tumours have been loosely referred to as genetic tumours when no
      obvious external cause was identifiable. In this study, the morphology of genetic
      tumours was detected by scanning electron microscopy (SEM) and the influence of
      exogenous phytohormones on genetic tumour growth was examined. Genetic tumours in
      Nicotiana hybrid were first observed in the hypocotyl area and later appeared
      from stems as a cluster complex. In vitro, genetic tumours were produced 5-6 days
      after explant treatment near each of the cut ends. The morphology of genetic
      tumours was investigated using SEM. Genetic tumours are mainly composed of
      epidermal cells surrounded by a well developed extracellular matrix (ECM), that
      is organized in a network linking surface cells. Globular structures containing
      several cells were formed from these clusters of epidermal cells. Vigorous
      tumourous growth from the leaf discs of the Nicotiana hybrid was obtained on
      medium supplemented with auxin and cytokinin at 0 to 10 muM, but 100 muM of auxin
      and cytokinin inhibited genetic tumour growth. Leaf discs treated with 10 muM
      cytokinin or auxin alone produced genetic tumours, but 10 muM cytokinin
      supplemented with 100 muM auxin stopped growth. Therefore genetic tumours are
      tissues that are, clearly, disturbed in endogenous hormone balance or have
      altered sensitivity to hormones and response to exogenous hormones.

PMID- 18627844
TI  - The ultrastructure of chondrocytes in the cartilage of Sepia officinalis and
      Octopus vulgaris (Mollusca, Cephalopoda).
AB  - Thin sections of cartilage from the chondrocranium of cuttle fish and octopus
      were examined using the transmission electron microscope. It was found that
      cephalopod chondrocytes differed considerably from the chondrocytes of vertebrate
      cartilage; in particular they possessed many long and ramifying cytoplasmic
      processes and had an ultrastructure typical of protein-secreting cells. They did
      not, however, contain secretory granules; while vesicles and rough endoplasmic
      reticulum cisternae seemed to open directly to the cell surface. The cell body
      and processes contained cytoskeletal structures: microtubules were easily
      recognized, but intermediate and thin filaments were difficult to make out as
      they were frequently clumped into bundles. Some chondrocytes contained
      conspicuous accumulations of hemocyanin. The cytoplasmic processes possessed
      intercellular contacts similar to gap junctions. Also present on processes and
      the cell body were cell-extracellular matrix focal adhesions. The chondrocytes
      were not polarized or arranged in any preferential spatial order, however, with
      their processes they formed a three-dimensional network throughout the cartilage
      tissue. Ultrastructural findings are discussed in relation to the singular
      morphofunctional characteristics of cephalopod cartilage which shares features
      with both the cartilage and bone of vertebrates.

PMID- 18627845
TI  - Cellular components and tunic architecture of the solitary ascidian Styela
      canopus (Stolidobranchiata, Styelidae).
AB  - Cell distribution and tunic morphology in the ascidian Styela canopus were
      examined by electron microscopy. The observations showed that the outer covering
      is composed of a thin sinuous cuticle with several protrusions and a deep layer
      of ground substance. The fibrous component and its arrangement in the tunic were
      demonstrated: elementary fibrils exhibit a 'microtubular' structure and an
      elliptical cross-sectional shape. Four types of cells were described: clear
      vesicular tunic granulocytes, tunic microgranulocytes, unilocular tunic
      granulocytes, and globular tunic granulocytes. Morphofunctional aspects of the
      tunic tissue and certain phylogenetic relationships are discussed.

PMID- 18627846
TI  - A comparison of cryo- versus chemical fixation in the soil green algae Jaagiella.
AB  - Chemical fixation protocols provided unsatisfactory preserved material for
      ultrastructural studies on Jaagiella alpicola Vischer (Chlorophyta). Instead,
      several methods of rapid freeze fixation followed by freeze substitution were
      applied. For fast freeze fixation, two methods were tried: plunge immersion
      freezing in liquid propane using a home-made device, and projection against a
      copper block cooled by either liquid nitrogen or liquid helium. Each method
      furnished well fixed material. The quality of the fixed samples was quite similar
      whether propane or the cryoblock cooled with liquid nitrogen was used. Liquid
      helium, however, provided superior results. After fixation the samples were
      cryosubstituted, using acetone or methanol as organic solvent with a chemical
      fixative added. Acetone gave better results than methanol as a substitution
      solvent when high temperature embedding was performed. The best cryosubstitution
      for ultrastructural studies was that in which osmium tetroxide or a mixture of
      osmium tetroxide and urany acetate was used.

PMID- 18627847
TI  - Structure of spermatodesms of Orthoptera Tettigonioidea.
AB  - Examination of spermatodesms collected from the male and female genital tracts of
      numerous Orthoptera Tettigonioidea revealed an overall morphological and
      ultrastructural organization that is generally similar in individuals of the same
      sex but considerably different between males and females of even the same
      species. In the male genital tracts each spermatodesm is composed of a limited
      number of spermatozoa whose nuclei and acrosomes are covered by a mucous cap. The
      spermatozoa inside each bundle are mainly arranged in parallel rows and are
      always distinctly separate. The number of spermatozoa per spermatodesm may vary
      within the same individual although it does not seem to exceed a maximum value
      that we could only determine exactly in Tettigoniidae species. The most
      characteristic feature of spermatozoa of all the species examined is a
      conspicuous elongation of the plasma membrane in the acrosomal region that is not
      present in the female genital tracts. In addition, spermatodesms from females are
      composed of highly numerous tightly packed spermatozoa that are linked together
      via the acrosomal region. This characteristic of spermatodesms, never previously
      reported in other insect species, would involve their reorganization during
      transfer from the male to the female genital tracts and would seem to take place
      in the spermatophore. The probable role of spermatodesms in the reproductive
      physiology of Tettigonioidea might be related to the degree of maturity of the
      sex cells transferred to the female; the reorganization of the spermatozoa out of
      the male genital tracts seems to support this hypothesis.

PMID- 18627848
TI  - Ultrastructural organization of seminal receptacle and sperm storage in Porcellio
      laevis latreille (crustacea: Isopoda oniscidea).
AB  - The seminal receptacle of Porcellio laevis is a specialized region of the genital
      tract placed at the confluence of the oviduct with the ovary. In virgin sexually
      mature females the seminal receptacle wall consists of a monolayered epithelium
      lying on a thin basal lamina and delimiting a narrow and anfractuous lumen. The
      cells are joined by cell junctions only in their apical portion and do not show
      marked secretory activity; numerous cells appear to undergo a partial or complete
      process of autophagy that preludes a remodelling of the seminal receptacle
      allowing it to receive and store a conspicuous number of spermatozoa. In mated
      females epithelial cells are characterized by wide intracellular spaces in their
      basal region, by an extensive development of smooth reticulum and by the release
      into the lumen of an abundant lipidic secretion. Some spermatozoa stored in the
      lumen are captured by pseudopodial-like protrusions produced by the epithelial
      cell surface and then drawn into cavities that form within the epithelial cells
      themselves. The spermatozoa stored in the seminal receptacle appeared to be well
      conserved and apparently able to fertilize even several months after
      insemination.

PMID- 18627849
TI  - Locations, ultrastructural morphology, and putative functions of the branchial
      podocytes of the fresh water crab Potamon niloticus - Savigy (crustacea,
      decapoda, potamonidae).
AB  - The gills of the African fresh water crab, Potamon niloticus, were investigated
      by transmission electron microscopy to verify the presence, outline the
      location(s) of, and describe the ultrastructural attributes of the branchial
      podocytes (BPs). Topographically, the cells were diffusely distributed in the
      gills. They were found at the arterial ends of the intralamellar spaces (ILSs),
      in the efferent hemolymphatic vessel (EHV), in the gill shaft, and in the
      marginal and central ILSs. In the EHV and the terminal ends of the ILSs, the BPs
      occurred in cohesive clusters of from three to eight large cells which were
      affixed to the vessel wall by small fibrocytic cells and bands of myofibrils. In
      the clusters, the BPs attached directly across interspersed junctional complexes
      (separated by wide intercellular spaces) and indirectly over a common basement
      membrane. Abundant heteromorphic, variably electron-dense vacuoles were scattered
      in the cytoplasm, apparently displacing the nuclei peripherally. The plasmalemma
      of the BPs were amplified into feet processes (pedicels) which inserted onto a
      basement membrane. The feet were joined by a thin unit membrane (diaphragm),
      leaving subcisternal spaces which contained flocculent to granular electron-dense
      material. The general ultrastructural morphology of the BPs of Potamon was
      similar to that of other crustaceans. However, atypically, a labyrinth of
      intercellular spaces (reckoned to be filtratory channels) was observed in the
      cell clusters. An ultrafiltration role was attested by the characteristic
      specializations of the plasmalemma and a phagocytic one inferred from the
      conspicuous intracytoplasmic vacuolation, presence of phagosomes, and overt
      necrosis and desquamation of the outlying cells of the clusters. The topographic
      location of the BPs in the EHV and at the terminal ends of the ILSs was perceived
      to be a strategic arrangement for promoting the detoxification and destruction of
      harmful materials and invasive agents which pass through the gills, an organ that
      presents an extensive surface area that interfaces with the ambient medium.

PMID- 18627850
TI  - Cytomorphological aspects on the response of the branchial heart complex of Sepia
      officinalis L. (cephalopoda) to xenobiotics and bacterial infection.
AB  - The ovoid cells of the branchial heart complex of Sepia officinalis L. were
      investigated with respect to their role in detoxification processes. The electron
      microscopical localization of in situ injected ferritin in the endocytotic
      lysosomal system, and the fluorescence microscopical localization of protein
      bound Evans blue in the ovoid cells of in vivo incubated animals, indicate that
      foreign materials are eliminated from the hemolymph by the branchial heart
      tissue. In addition to the non-circulating ovoid cells of the branchial heart,
      hemocytes in the circulating blood and in the wall of the branchial heart are
      also involved in the incorporation of allogeneic substances and bacteria, or
      their debris. Based on these observations, we propose that the ovoid cells,
      together with circulating and adhesive hemocytes in the branchial hearts, are an
      important component of a more comprehensive defence and detoxification system in
      dibranchiate cephalopods that prevents contamination of the whole organism by
      endocytotic removal of noxious substances from the hemolymph.

PMID- 18627851
TI  - Ultrastructural and cytochemical aspects of the basophilic cells in the
      hepatopancreas ofAplysia depilans(Mollusca, Opisthobranchia).
AB  - The basophilic cells ofAplysia depilanshave a pyramidal shape and a large nucleus
      usually located near the center or in the basal half of the cell. The nucleus
      possesses several clumps of condensed chromatin and a prominent nucleolus. The
      great profusion of rough endoplasmic reticulum cisterns in a major feature of
      these cells. Secretion granules are accumulated in the apical zone, and
      arylsulphatase was detected in some of them. In some basophilic cells a very
      substantial part of the cell volume was occupied by clear vacuoles, some of them
      reaching 9 mum. However, in other cells only a few vacuoles were observed.
      Probably the cells with just a few vacuoles are still young, and after a
      progressive accumulation, the vacuoles become abundant in old cells. The presence
      of a dark nucleus in the cells with a large number of vacuoles suggests that they
      are in a final stage of their life. Arylsulphatase was detected in the vacuoles
      and also in small secondary lysosomes containing substances in digestion. Bundles
      of tubules with 50 nm in diameter were found within some cisterns of rough
      endoplasmic reticulum. A cell fraction enriched in mannitol oxidase, extracted
      from the hepatopancreas of a terrestrial slug, consisted in very similar tubular
      structures. Using a histochemical method, mannitol oxidase was detected in the
      basophilic cells ofA. depilans, and it may be associated with the tubular
      structures of the endoplasmic reticulum. This is the first report of mannitol
      oxidase in opisthobranch molluscs. Almost spherical peroxisomes with a small
      nucleoid were abundant in these cells. The nucleoids presented a rectangular
      section, but a crystalline structure was not evident. The peroxisomes were
      stained after the cytochemical detection of catalase activity.

PMID- 18627852
TI  - Cadmium pathology in an insect cell line: ultrastructural and biochemical
      effects.
AB  - Cadmium (Cd) pathology was studied in an insect cell line (Aedes albopictusC6/36)
      at the ultrastructural level. The most prominent pathological changes occurred at
      the level of the nucleus: chromatin clumping, indentations, filling and
      dilatation of the perinuclear cisternae and an increased amount of bound
      ribosomes were observed. In the cytoplasm, condensation and swelling of
      mitochondria, increase of both free and membrane-bound ribosomes, filling and
      dilatation of the rough endoplasmic reticulum, and increase of the lysosomal
      system were the most conspicuous effects. The increased content of the
      perinuclear and cytoplasmic cisternae was probably due to an increased protein
      synthesis or a disturbance of the protein export system. This picture differed
      clearly from the osmotically swollen electron-lucent cisternae that have been
      described in other pathological situations. The enhancement of the lysosomal
      system was paralleled by a slight but significant stimulation of the acid
      phosphatase activity in the sublethal Cd concentration range. In vitro
      experiments suggested that Cd probably acts directly on this enzyme. Abnormal
      medium acidification in cultures treated with low Cd levels was correlated with
      an increased production of lactic acid. Together with the morphological data,
      this suggested a Cd-induced impairment of the aerobic metabolism.

PMID- 18627853
TI  - Ultrastructure of lamellae, mineral and matrix components of fish otolith twinned
      aragonite crystals: implications for estimating age in fish.
AB  - Atomic force microscopy (AFM) of the crystalline ultrastructure of otoliths
      fromPagrus major(Sparidae),Macruronus novaezelandiae(Merlucciidae),Oncorhynchus
      tshawytscha(Salmonidae),Sebastes alutus(Scorpaenidae), andHoplostethus
      atlanticus(Trachichthyidae) showed regular deposition of lamellae in the size
      range 13-490 nm. The orientation of lamellae in the {010} plane was the same as
      lamellae in crystals of mineral aragonite. Lamellae in mineral aragonite were in
      the size range 15-45 nm. Lamellae observed in the otolith ofM. novaezelandiaeby
      transmission electron microscopy showed a range of widths (25-225 nm) similar to
      lamellae observed by AFM. The observed lamella widths were in the size range that
      has been described for sub-daily and daily microincrements in otoliths. Observed
      lamellae widths were also in the size range of alpha-recoil trajectories
      of(222)Rn and provide a potential diffusion sink correction for the(222)Rn losses
      in radionuclide method of ageing otoliths. Comparison of the orientations of
      lamellae to templates based on the Bragg unit cell structure of twinned aragonite
      indicated that the lamellae resulted from polysynthetic twinning on the {010}
      aragonite crystal face. Additional cyclic twinning occurred on the {110} face of
      the aragonite crystal and sometimes led to pseudohexagonal crystals, whose sizes
      were orders of magnitude larger than lamellae. The organic matrix of the otolith
      was visible by atomic force and transmission electron microscopy at the nanometer
      level of resolution, but the organic matrix was confined to the {110} twinning
      plane of symmetry of the otolith crystal.

PMID- 18627854
TI  - Femoral chordotonal organ in the legs of an insect,Chrysoperla
      carnea(Neuroptera).
AB  - The femoral chordotonal organ (FCO) inChrysoperla carneais situated in the distal
      part of the femur and consists of two scoloparia, which are fused at their distal
      end. The distal scoloparium contains 17-20 scolopidia, and the proximal one six
      scolopidia. Each scolopidium consists of two sensory cells and three types of
      enveloping cells (glial, scolopale and attachment cell). The sensory cells of
      different scolopidia do not lie at the same level in the FCO. Therefore the
      attachment cells of different scolopidia have different lengths. In the FCO,
      three types of ciliary roots are found in different sensory cells. The dendrite
      of the sensory cell terminates in a distal process, which has the structure of a
      modified cilium (9x2+0). The very distal part of the cilium is surrounded by an
      extracellular electron dense material, the cap, and ends in a terminal dilation.
      The scolopale cell contains the electron dense scolopale rods, consisting of
      plentiful microtubules. In their middle third the scolopale rods are fused and
      form the scolopale. In the FCO septate junctions, desmosomes and hemidesmosomes
      are found.

PMID- 18627855
TI  - Ultrastructure of the male accessory glands ofAllacma fusca(Insecta, Collembola).
AB  - The accessory glands ofAllacma fusca(L.) (Insecta, Collembola, Sminthuridae)
      consist of a series of secretory units that are arranged in parallel and open
      into the ejaculatory duct. Each unit is composed of microvillate cells stacked
      around a common cavity. Basal cells are involved in ion-control of fluids from
      the hemocoel to the cavity. The intermediate and apical cells, which have a
      laminar appearance and contain many microtubules, are involved in the structural
      integrity of the unit. Supporting cells ensheath the most apical cells. Large
      openings in the cuticle allow the gland secretion to flow into the ejaculatory
      duct lumen. These openings are protected by a porous cuticle different from that
      lining the epithelium of the ejaculatory duct. Conspicuous muscle fibers run
      along the lateroventral side of the ejaculatory duct beneath the insertion of the
      accessory glands. The fine structure of the accessory glands indicates that they
      are type I ectodermic glands as defined by Noirot & Quennedey (1974). Their
      function could be to control the fluidity of the material for spermatophore
      formation and to ensure the proper physiological conditions for spermatozoa
      stored in the ejaculatory duct lumen.

PMID- 18627856
TI  - Accumulation of daunomycin and fluorescent dyes by drug-transporting Malpighian
      tubule cells of the tobacco hornworn, Manduca sexta.
AB  - Insect Malpighian tubules actively transport a variety of xenobiotics, and it has
      been proposed that P-glycoprotein (P-gp), or the multidrug transporter, is
      involved. To test this idea, we observed the interaction of known P-gp substrates
      with isolated, living Malpighian tubules from tobacco hornworm (Manduca sexta)
      larvae. Specifically, the fluorescent drugs daunomycin, rhodamine 123, acridine
      orange and Hoechst 33342 were applied to the basal side of tubules (proximal
      portion) in a well of fluid on a coverslip; the subsequent distribution of the
      drugs was monitored by laser scanning confocal microscopy. Contrary to
      expectation, none of the drugs appeared in the lumen even after 1-2 h of
      incubation, although the cells of the tubule were intensely stained within 1 min.
      For daunomycin, neither verapamil, a P-gp inhibitor, nor nicotine, an alkaloid
      which appears to be transported by a P-gp-like mechanism in this species, had any
      effect on the pattern of staining. In sharp contrast to the fast and intense
      staining of Malpighian tubules, portions of muscle, nerve cord and body fat
      showed only light staining with daunomycin, and only after prolonged periods. The
      results suggest that for some drugs, Malpighian tubules act as xenobiotic
      scavengers, and that this property is unrelated to P-gp-mediated transport.

PMID- 18627857
TI  - Evidence for high molecular weight proteins in arthropod gap and smooth septate
      junctions.
AB  - The proteins that make up arthropod gap and septate junctions have not been
      identified with any certainty. Several candidate proteins for both types of
      junctions have been proposed in the literature, but there has been no agreement
      on any of these. Arthropod gap junctions do not label with antibodies to
      vertebrate gap junction connexins; it thus appears that unrelated proteins form
      these rather similar structures. Gap junctions inManduca sextamidgut epithelium
      are unusual since they function only during the molt and are non-functioning
      during the larval instars. We have developed a preparation from this tissue that
      is highly enriched in both gap and smooth septate junctions when examined by
      electron microscopy. SDS-PAGE gels of this preparation have two major protein
      bands, at 75 and 90 kDa. The presence of gap junctions correlates best with the
      75 kDa protein and smooth septate junctions with the 90 kDa protein. Further, the
      75 kDa band is stained by an antibody to a putative gap junction protein fromC.
      elegans. We propose that the 75 kDa protein is a major structural component of
      gap junctions inManduca sextamidgut epithelium and that the 90 kDa protein forms
      the smooth septate junctions.

PMID- 18627858
TI  - Peritrophic membrane structure and formation of larvalTrichoplusia niwith an
      investigation on the secretion patterns of a PM mucin.
AB  - Peritrophic membrane or matrix (PM) secretion and formation patterns were
      examined in the cabbage looper larvae (Trichoplusia ni[Hubner]) by transmission
      and scanning electron microscopy (SEM). PM first became visible in the lumen
      between tips of the microvilli and the stomodeal valves as a single layered
      fibrous structure that became more compact in appearance in the middle and
      posterior mesenteron. In the anterior mesenteron, nascent PM was visible within
      the brush border as a fibrous linear structure that contained both the major PM
      matrix protein, invertebrate intestinal mucin (IIM) and chitin-containing
      structures. Even though delamination events were confined to the anterior
      mesenteron, IIM was secreted by columnar epithelial cells throughout the length
      of the mesenteron. SEM of the midgut epithelium revealed PM covering individual
      epithelial cells.

PMID- 18627859
TI  - The ultrastructural effect and subcellular localization of mercuric chloride and
      methylmercuric chloride in insect cells (Aedes albopictusC6/36).
AB  - Abstract.The ultrastructural effects of mercuric chloride (Hg) and methylmercuric
      chloride (MeHg) were studied in theAedes albopictusC6/36 cell line. Both metal
      salts caused nuclear indentations, chromatin clumping and proliferation of the
      nucleolus. The mitochondria became pleomorphous. An increase of both free and
      membrane-bound ribosomes, swelling of the rough endoplasmic reticulum caused by
      accumulated protein and the appearance of well developed Golgi stacks all
      indicated the activation of protein synthesis. The activation was probably a
      cellular response to general stress, and the synthesized proteins may be members
      of the heat shock protein family. Apart from these common ultrastructural
      features, Hg-treated cells showed typical clusters of small electron-lucent
      vacuoles near the Golgi stacks. In cells exposed to MeHg, cytoplasmic tube-like
      structures were often observed and the disorganization of the organelles together
      with the appearance of blebs suggested disruption of the microtubules. Mercury
      accumulation was localized by an autometallographical silver staining technique
      both at the light and electron microscopic level; silver deposits were quantified
      by image analysis. For both Hg- and MeHg-treated cells, the degree of silver
      staining increased rapidly with increasing exposure time, but a considerable
      heterogeneity within the cell population was found. Lysosomes proved to be the
      major mercury storage sites in theAedescells and silver deposits could already be
      found after 30 min of Hg treatment. At sublethal concentrations, Hg inhibited the
      lysosomal marker enzyme acid phosphatase to some extent. For MeHg, no effect on
      this enzyme was found.

PMID- 18627861
TI  - Ultrastructural study of spermatozoa of the neotropical lizards, Tropidurus
      semitaeniatus and Tropidurus torquatus (Squamata, Tropiduridae).
AB  - A detailed description of the sperm ultrastructure of Tropidurus semitaeniatus
      and T. torquatus is provided. Mature spermatozoa of T. semitaeniatus and T.
      torquatus are filiform and characterized by: apical portion of acrosome
      depressed; perforatorium single; epinuclear lucent zone well developed; midpiece
      short; mitochondria columnar; midpiece with three sets of alternating ring
      structures and mitochondria (rs1/m1, rs2/m2, rs3/m3); nuclear shoulders rounded;
      nucleus elongate; fibres 3 and 8 enlarged; and fibrous sheath in midpiece.
      Spermatozoa ofTropidurus are unusual in possessing a unilateral electron-lucent
      ridge at the surface of the acrosome and an epinuclear electron-lucent zone. The
      two species are very similar, differing in details such as degree of acrosome
      flattening, presence of bulging at nuclear base, and arrangement of microtubules
      in the endpiece. Comparisons between Tropiduridae and other families of iguanian
      lizards are made.

PMID- 18627862
TI  - Ultrastructural localization of enzymatic activity during spermiogenesis in two
      phytophagous bugs (Hemiptera: Pentatomidae).
AB  - Ultrastructural cytochemical techniques were used for the localization of
      phosphatases and oxidases in spermatid and spermatozoon of the phytophagous bugs
      Acrosternum aseadum and Nezara viridula (Hemiptera: Pentatomidae). Acid
      phosphatase was found mainly in the trans most portion of the Golgi complex, and
      in the acrosome of spermatozoon. Glucose-6-phosphatase was located in the
      endoplasmic reticulum, trans portion of the Golgi complex and in the acrosome of
      spermatids. The axoneme showed activity of acid phosphatase, glucose-6
      phosphatase and thiamine pyrophosphatase. This observation supports the idea that
      various phosphates may play some role in spermatid differentiation. Indeed, the
      presence of cytochrome oxidase activity was only shown in the mitochondrial
      cristae of early spermatids, suggesting also the participation of this enzyme
      during spermatid differentiation of this insect.

PMID- 18627863
TI  - A morphological study on posterior gills of the mangrove crab Ucides cordatus.
AB  - Morphological and histological studies on posterior gills of the mangrove crab
      Ucides cordatus showed that the 5th gill (of 7) has a larger surface area and a
      greater number of lamellae compared to the 6th gill. Regular separation of gill
      lamellae, important when the gill is in air, is maintained by enlargements of the
      marginal canals. Conical, spine-like structures along the efferent vessel of both
      5th and 6th gills were also observed. In addition, pillar cells, a discontinuous
      lamellar septum and a hypobranchial artery were observed. The presence of valve
      like structures near the efferent vessel was also indicated. These structures,
      together with the pillar cells, may have a role in directing the hemolymph flow
      towards certain gills during particular physiological states. Localization of
      osmoregulatory epithelia in the lamellae of both gills was inferred from
      dimethylaminostyrylethylpyridiniumiodine staining. Apparently gills 5 and 6 have
      osmoregulatory epithelial cell patches of similar area, corresponding to 43% and
      38% of the total lamellae area, respectively. However, their localization is
      quite different. Gill number 5 osmoregulatory patches seem to be restricted to
      the afferent region of the lamella whereas in gill number 6, they are more
      dispersed over the entire lamella. These differences may be related to the
      particular functional characteristics of these gills.

PMID- 18627864
TI  - An ultrastructural study of the prostate gland of megascolicid earthworm Lampito
      mauritii (Kinberg).
AB  - The ultrastructure of prostate gland of Lampito mauritii revealed two types of
      secretory cells. Type 1 cells with a broad basal region and a long apical region
      contain electron dense oval secretory granules with an increased density at the
      core region. Numerous electron lucent granules with fine filamentous and electron
      dense amorphous materials also occur at the basal region of these cells. Type 2
      cells contain electron lucent mucous-like secretory granules. This cell type
      contains exceptionally large Golgi complexes having 20-23 stacked cisternae. Both
      cell types open into a common lumen and numerous microtubules are visible at the
      apical end. Junctional complexes, such as desmosomes and septate junctions, are
      observed in this glandular tissue.

PMID- 18627865
TI  - Structure and energy pathways of spermatozoa of the rove beetle Aleochara
      bilineata (Coleoptera, Staphylinidae).
AB  - The morphology of mature spermatozoa of the rove beetle Aleochara bilineata was
      examined by using scanning and transmission electron microscopy. They are about
      1000 mum long and filiform. The acrosome and the nucleus are elongate and each
      about 20 mum long. A well-developed centriole adjunct region connects the nucleus
      with the sperm tail. The axoneme reveals the 9 + 9 + 2 pattern of the pterygote
      sperm flagellum. Two accessory bodies and two mitochondrial derivatives with
      paracrystalline inclusions are present. Cristae are reduced to the cortical zone
      of the derivatives. Cytochrome-c oxidase activity was detected within the cristae
      by DAB-reaction. The energy metabolism of the spermatozoa was investigated by
      using different inhibitors affecting the mitochondrial and cytoplasmic metabolic
      pathways. Sperm movement was used as an indicator for the utilization of ATP by
      the axoneme. In control experiments, the duration of motility was longer than 45
      min. In the presence of atractyloside or potassium cyanide the motility duration
      was not affected. On the other hand, iodoacetic acid in the medium stopped sperm
      motility within 15 min. This indicates that sperm energy metabolism mainly
      depends on the glycolytic pathway.

PMID- 18627866
TI  - Some cytological features of follicle cells in an ovariole of the carpenter bee
      (Xylocopa virginica virginica) (L) (Hymenoptera: Apidae).
AB  - In an attempt to provide some essential basic data, currently very sparse, on the
      ultrastructure of solitary bees, the histology, cytology and ultrastructure of
      thin and ultrathin sections of ovarioles of the adult carpenter beeXylocopa
      virginica virginica were studied with the light and transmission electron
      microscopes. The work revealed an apparently previously unreported occurrence of
      intracellular paired membrane configurations in follicle cells of an ovariole and
      confirmed the presence in follicle cells of somatic intercellular bridges
      previously reported in follicle cells in a variety of bees, but not in the
      carpenter bee. Microtubules and bacteroids were also seen in the follicle cells.

PMID- 18627867
TI  - Spermiogenesis in Seison nebaliae (Rotifera, Seisonidea): further evidence of a
      rotifer-acanthocephalan relationship.
AB  - The spermatozoa of Seison nebaliae are filiform cells about 70 mum long with a
      diameter of 0.6 mum. They have a slightly enlarged head, 2.5 mum long, followed
      by a long cell body. The flagellum starts from the head, and runs parallel to the
      cell body, contained in a groove along it. The head contains an acrosome, two
      large, paired para-acrosomal bodies, the basal body of the flagellum and the
      anterior thin extremity of the nucleus. The cell body contains the main portion
      of the nucleus, a single mitochondrion located in its distal portion, and many
      accessory bodies with different shapes. The flagellum has a 9 + 2 axoneme. The
      study of spermiogenesis shows the Golgian origin of the acrosome and the para
      acrosomal bodies and reveals some peculiarities: a folding of the perinuclear
      cisterna is present between the proacrosome and the basal body of the flagellum
      in early spermatids and the flagellum runs in a canal inside the spermatid
      cytoplasm. The basal body migrates anteriorly. These characters are shared partly
      by the Rotifera Monogononta and, to a large extent, by the Acanthocephala studied
      so far. Many details of the spermiogenetic process are identical to those of
      Acanthocephala, thus suggesting that the processes in the two taxa are
      homologous.

PMID- 18627868
TI  - Ovarian follicular atresia in two teleost species: a histological and
      ultrastructural study.
AB  - Follicular atresia is a common phenomenon in vertebrate ovaries involving the
      oocyte and the follicular wall degeneration. Female Astyanax bimaculatus
      lacustris and Leporinus reinhardti were kept in aquaculture cages inside tanks
      from February 1994 to January 1995 for the study of the characteristics of
      different stages of follicular atresia. Histological and ultrastructural analysis
      demonstrated similarities in the degenerative events and in the resorption of
      oocytes in both species. Degradation of organelles, such as mitochondria,
      cortical alveoli, and annulate lamellae occurred in the peripheral ooplasm during
      the initial stage of the process. Follicle cells showed marked phagocytic
      activity with digestive vacuoles, myelin figures, and lipofuscin granules during
      the intermediate and advanced stages of follicular atresia. Granulocytes were in
      activity during the final stage of follicle resorption. The duration of
      follicular atresia was 4 months in Leporinus reinhardti and 7 months in Astyanax
      bimaculatus lacustris. When submitted to induced reproduction in December 1995,
      50-60% of the females of both species responded to induced spawning, indicating
      the recovery of gonadal activity. It is suggested that, in captive conditions,
      follicular atresia is shorter in total-spawning fishes when compared to those
      showing partial spawning, and that it has no apparent deleterious effects on
      induced reproduction in the subsequent cycle.

PMID- 18627869
TI  - Barrier cells in gills of the alligator gar.
AB  - Studies of barrier cells in fishes are few and have been restricted primarily to
      salmonids. Moreover, these studies revealed the presence of barrier cells only in
      hematopoietic and lymphoid organs. The alligator gar, Lepisosteus spatula,
      possesses similar tissues within the gills which are readily accessible;
      therefore, they were the organs of choice. An electron microscopical analysis of
      the gills was undertaken to determine if barrier cells exist and if they possess
      an ultrastructural design comparable to their counterparts in the brain and lungs
      of higher vertebrates and hematopoietic/lymphoid tissues in fishes. The present
      study revealed that barrier cells were found only within non
      hematopoietic/lymphoid areas. Barrier cells surrounded endocrine components,
      nerves, and sinusoids rather than capillary endothelium or hematopoietic/lymphoid
      tissues. Barrier cells in the alligator gar displayed a complex envelopment more
      similar to those found in the blood-cerebrospinal fluid, blood-brain, and blood
      gas barriers in higher vertebrates than in salmonids. The barrier in the
      alligator gar consisted of: (1) an endothelium whose cells displayed tight
      junctions; (2) a basement membrane; and (3) an outer adventitia composed of
      fibrocytic cells in syncytium.

PMID- 18627870
TI  - Na(+)/K(+)-ATPase activity and immunocytochemical labeling in podobranchial
      filament and lamina of the freshwater crayfish Astacus leptodactylus Eschscholtz:
      evidence for the existence of sodium transport in the filaments.
AB  - In the crayfish Astacus leptodactylus, the podobranch, bearing respiratory and
      ion-transporting filaments, is attached to the lamina. The Na(+)/K(+)-ATPase
      activity is higher in filaments than in lamina. Using a mouse monoclonal antibody
      directed against the alpha subunit of Na(+)/K(+)-ATPase, and indirect
      immunofluorescence microscopy, we can observe that the immunoreactivity of the
      antibody is different for each kind of structure. The lamina presents an ion
      transporting type epithelium, which is thick and presents a developed apical
      infolding system but no developed basolateral infolding system. The
      immunoreactivity of the antibody in the lamina is very weak. Respiratory
      filaments present a thin epithelium with a few small apical folds and scarce
      mitochondria. The immunoreactivity of the antibody in the respiratory filaments
      is very weak. In contrast, the ion-transporting filament epithelium is thick,
      presents a short apical infolding system, a well-developed basal infolding
      system, and numerous mitochondria. The immunoreactivity of the antibody in the
      ion-transporting filaments is strong. Ion-transporting filaments, which have a
      cuticle permeable to cations, seem particularly implicated in Na(+)regulation, by
      way of the sodium pump.

PMID- 18627871
TI  - Ultrastructure of the germ cells in the testis of matrinxa, Brycon cephalus
      (Teleostei, Characidae).
AB  - This study describes at ultrastructural level the germ cells in the testis of
      matrinxa (Brycon cephalus) raised in captivity. The specimens 'matrinxa' were
      maintained in four breeding tanks of 200 m(2), at the Aquaculture Research Center
      at Vale do Ribeira-CEPAR, from Fishery Institute, in Pariquera-Acu City, Sao
      Paulo, Brazil. The samples were collected from March 1994 to February 1996. The
      testis has been classified as tubular unrestricted spermatogonial type, in which
      four stages of germ cells can be distinguished as follows: spermatogonia,
      spermatocytes (primary and secondary); spermatids and spermatozoa.

PMID- 18627872
TI  - The ultrastructure of Sorubim lima (Teleostei, Siluriformes, Pimelodidae)
      spermatogenesis: premeiotic and meiotic periods.
AB  - The ultrastructure of Sorubim lima spermatogenesis during the premeiotic and
      meiotic periods was studied. Our observations showed that the germ cells in the
      cysts are connected by cytoplasmic bridges and the mitotic and meiotic divisions
      are slightly asynchronous. The first and the last spermatogonial generations
      differ in the cellular and nuclear volume, nucleolus, chromatin condensation,
      distribution, size, density, and shape of the mitochondria, presence of 'lamellae
      anulata', amount and dimension of the 'nuages', and movement of the centrioles.
      In addition to the nuclear prophase structures, the spermatocyte I shows changes
      in all other cellular organelles and elongated vesicles appear in the cytoplasm.
      The accentuated cytoplasmic density and thickened walled vesicles are
      morphological characteristics that differentiate spermatocytes II from the other
      germ cells in the cysts of Sorubim lima testis.

PMID- 18627873
TI  - Structural changes in spinal ganglion neurons of lizards after cold-exposure.
AB  - We studied structural changes in spinal ganglion neurons that occur in lizards
      exposed to the cold, both at the light and electron microscope levels. Two types
      of perikaryal changes were found in the cold-exposed animals: (a) In 25% of all
      ganglion neurons, the central region of the perikaryon was devoid of Nissl bodies
      and a narrow peripheral zone stained deeply basophilic. Electron microscopic
      examination of these cells showed that mitochondria, Golgi complexes and other
      organelles were assembled in the central region of the perikaryon, while most
      cisternae of granular endoplasmic reticulum and free polysomes were confined to
      the periphery of the perikaryon. These changes seem to take place mainly in dark
      neurons. (b) In 8.6% of all ganglion neurons, Nissl bodies were present
      throughout the perikaryon, but separated by large, clear spaces. Under the
      electron microscope, these clear spaces were filled with large numbers of densely
      packed filaments. It seems that mainly light neurons undergo this type of
      structural change. The degree of nuclear eccentricity was significantly greater
      in the neurons of cold-exposed animals than in controls. The nucleolar volume was
      significantly increased and both the percentages of nuclei with two nucleoli and
      of nuclei with 'vacuolated' nucleoli were significantly greater in neurons
      displaying structural changes than in the other neurons. The structural
      modifications observed in spinal ganglion neurons of cold-exposed lizards closely
      resemble those seen in the same lizard neurons following axonal section. They
      could be due to a) metabolic changes induced by low temperature and fasting, b)
      alterations in the flow of nerve impulses from the periphery, or c) impaired
      retrograde transport of trophic substances from the periphery to the cell body.

PMID- 18627874
TI  - Granular cutaneous glands in the frog Physalaemus biligonigerus (Anura,
      Leptodactylidae): comparison between ordinary serous and 'inguinal' glands.
AB  - Beside the ordinary granular (or serous) glands, the skin of the leptodactylid
      frog Physalaemus biligonigerus possesses peculiar clusters of large granular
      units, the 'inguinal' glands, located in the dorsolateral areas of the pelvic
      girdle. Both gland types store their specific products within the syncytial
      cytoplasm of the secretory unit. These secretory materials consist of spheroidal
      or ellipsoidal bodies (granules) with a repeating substructure. The subcellular
      features of the immature products of the ordinary serous and inguinal glands are
      identical. However, these products undergo divergent maturative processes,
      leading to fluidation on the one hand and condensation on the other. Secretory
      release into the small gland lumen was observed in both cases, involving
      merocrine mechanisms. On the basis of the analysis of cutaneous serous gland
      polymorphism in anurans, the inguinal units in P. biligonigerus do not appear to
      be an independent line. Rather, these large units belong to the ordinary serous
      type and represent a gland population specialized in the storage of remarkable
      amounts of product used in chemical defence of the skin.

PMID- 18627875
TI  - Formation of the karyosome in developing oocytes of weevils (Coleoptera,
      Curculionidae).
AB  - A complex structure termed the karyosome forms in the nuclei of the developing
      oocytes of Anthonomus pomorum, Hylobius abietis and Phyllobius sp. (Coleoptera:
      Curculionidae). It is composed of highly condensed chromosomes, fused with an
      electron-dense granular material. There are two types of nuclear body associated
      with the karyosome. The smaller bodies are found in the immediate vicinity of the
      karyosome. The larger, and more electron-dense, bodies originate next to the
      condensing chromosomes. During vitellogenesis, the latter bodies disperse in the
      karyoplasm, and at least some of them locate in the characteristic irregular
      projections of the germinal vesicle. Morphologically, these projections resemble
      the accessory nuclei described in other insects. In the studied species, a
      proteinaceous sheath, the so-called karyosome capsule, surrounds the karyosome.
      The formation of the karyosome and its capsule occurs during previtellogenesis,
      so that these structures are fully formed at the onset of vitellogenesis. An
      extraction of the oocyte cytoplasm with Triton X-100 showed that the material
      constituting the karyosome capsule is filamentous. Staining with rhodamine
      conjugated phalloidin reveals large amount of F-actin in the karyosome capsule.

PMID- 18627876
TI  - Hexagonal columnar liquid crystal in the cells secreting spider silk.
AB  - The liquid crystallinity of spider dragline silk dope is thought to be important
      for both the spinning process and the extreme mechanical properties of the final
      thread. Although the formation of the liquid crystalline units is poorly
      understood, it has been suggested that spider silk proteins are secreted in a
      random coil and then aggregate end-to-end into rod-shaped units to form
      supramolecular liquid crystals. However, evidence presented here from
      transmission electron microscopy indicates that coat protein of the dragline silk
      of a Nephila spider is stored as hexagonal columnar liquid crystals within the
      intracellular secretory vesicles. This implies that this component is already
      folded into short rods within the gland cells and forms molecular rather than
      supramolecular liquid crystals.

PMID- 18627877
TI  - Ultrastructure of spermiogenesis in Plagioscion squamosissimus (Teleostei,
      Perciformes, Sciaenidae).
AB  - Spermiogenesis in Plagioscion squamosissimus occurs in cysts. It involves a
      gradual differentiation process of spermatids that is characterized mainly by
      chromatin compaction in the nucleus and formation of the flagellum, resulting in
      the spermatozoa, the smallest germ cells. At the end of spermiogenesis, the cysts
      open and release the newly formed spermatozoa into the lumen of the seminiferous
      tubules. The spermatozoa do not have an acrosome and are divided into head,
      midpiece, and tail or flagellum. The spermatozoa of P. squamosissimus are of
      perciform type with the flagellum parallel to the nucleus and the centrioles
      located outside the nuclear notch.

PMID- 18627879
TI  - Transcription terminators in lambda. Appendix. Deletion of control sites in the
      pL operon of phage lambda.

PMID- 18627880
TI  - In vitro synthesis and characterization of DNA complementary to potato spindle
      tuber viroid.
AB  - When DNase-digested calf thymus DNA is used as primer, the RNA-directed DNA
      polymerase of avian myeloblastosis virus will accept potato spindle tuber viroid
      (PSTV) as a template for DNA synthesis. The DNA obtained hybridizes specifically
      to PSTV and low molecular weight RNA isolated from PSTV-infected plants; no
      hybridization to unrelated viral RNAs or tow molecular weight RNA isolated from
      uninoculated host plants was detectable. Purified PSTV cDNA is heterogeneous in
      length, but the mean chain length is approximately one-fourth that of PSTV. The
      kinetics of PSTV PSTV cDNA hybridization and the thermal denaturation profile of
      the resulting hybrids are consistent with the known molecular weight (1.27 x
      10(5)) and G + C content (54.7%) of PSTV.

PMID- 18627881
TI  - Measurement of viroid sequence homology by hybridization with complementary DNA
      prepared in vitro.
AB  - DNA complementary to potato spindle tuber viroid (YSTV cDNA) has been used in RNA
      DNA hybridization experiments to study PSTV replication in a variety of hosts and
      to measure the amount of sequence homology between YSTV and several independently
      isolated viroids. When PSTV cDNA was hybridized with low molecular weight RNA
      isolated from PSTV-infected tomato at different times after inoculation, PSTV .
      PSTV cDNA hybrids were detectable before symptoms began to appear. Low molecular
      weight RNA was prepared from PSTV-infected tomato, tobacco, Gynura, and
      chrysanthemum and was analyzed by polyacrylamide gel electrophoresis and
      hybridization to PSTV cDNA. The identical electrophoretic mobility of PSTV
      isolated from each host and identical thermal stability of the corresponding RNA
      DNA hybrids suggest that host-specific changes in viroid sequence do not occur.
      Previously unreported viroids have been isolated from Columnea erythrophae and
      from a random selection of Solanum phureja and S. stenotomum introductions. The
      electrophoretic mobility of the Solanum viroids is very similar to that of PSTV,
      whereas the Columnea viroid and the previously reported chrysanthemum stunt
      viroid migrate significantly faster than PSTV. Measurement of the degree of
      sequence homology between PSTV and the various viroid isolates suggests that
      whereas the Solunum viroids are closely related to PSTV, chrysanthemum stunt and
      Columnea viroids are not closely related to PSTV.

PMID- 18627882
TI  - Nucleotide sequence of cucumber mosaic virus-associated RNA 5.
AB  - The complete nucleotide sequence of cucumber mosaic virus-associated (satellite)
      RNA 5 (CARNA 5) strain D has been determined. The molecule is 335 residues long
      and is capped at its 5' extremity. There were minor variations in the sequence of
      different preparations of the satellite RNA. Otherwise, no unusual features of
      secondary structure or sequence are present. CARNA 5 (D) contains a number of
      possible initiation and termination codons for protein synthesis. Study of CARNA
      5 isolated from other strains of cucumber mosaic virus suggests that sequence
      variation of the molecule from one strain to another is very limited.

PMID- 18627883
TI  - The stabilization of the particles of turnip rosette virus. III. Divalent
      cations.
AB  - Particles of turnip rosette virus (TRosV) contain 1-2 Ca2+ and about 1 Mg2+ ion
      per protein subunit. However, Ca2+ was much more efficient than other cations
      tested at stabilizing TRosV particles. Binding studies showed that at pH values
      of 5 and 6, TRosV particles bound 1 Ca2+ per protein subunit and, at pH 8.25,
      about 3 Ca2+; the Ca2+ was bound more firmly at lower pH values. Other cations
      competed poorly or not at all for the high affinity Ca2+ binding site.
      Preliminary results indicate that the cation stabilization of southern bean
      mosaic virus is similar to that of TRosV.

PMID- 18627884
TI  - Intermediates in the disassembly of tobacco mosaic virus at alkaline pH
      Infectivity, self-assembly, and translational activities.
AB  - Disassembly of tobacco mosaic virus at alkaline pH produces a series of discrete,
      kinetically metastable rods of intermediate length, all containing the original
      3'-terminus, together with a "stable fraction" of apparently undegraded virus.
      The physical properties of these various rods and their protected RNAs were
      already known and some biological properties are now described. The stable
      fraction of rods was found to have an infectivity less than 5% of that of the
      control virus, irrespective of whether or not it had been treated with
      micrococcal nuclease after exposure to the alkaline conditions. This residual
      infectivity was probably due to contamination with some remaining undegraded
      virus. In the wheat germ cell-free protein synthesis system, the RNA from the
      stable fraction that had not been treated with micrococcal nuclease, and which
      still contained the 5'-terminal "cap" structure m7G(5')ppp(5')G, was translated
      indistinguishably from control viral RNA. The RNAs from the nuclease-treated
      stable fraction and from the other partly stripped particles were translated only
      with greatly reduced efficiency, but the fragment containing the 2,000
      nucleotides from the 3' end of the original RNA yielded disproportionate amounts
      of a 30,000-dalton polypeptide. Reassembly with the viral coat protein occurred
      readily only with those fragments of the RNA longer than about 1,400 nucleotides
      from the 3'-terminus, consistent with earlier evidence that the nucleation site
      for virus assembly is about 1,000 nucleotides from the 3' end. Paradoxically,
      however, the RNA from the nuclease-treated stable fraction, which lacks only a
      few nucleotides from the 5' end of the native viral RNA, would not reassemble.
      The reason for this is unclear, but change in the secondary structure of the RNA
      in the assembly initiation region is a possible explanation.

PMID- 18627885
TI  - Analysis of baculovirus genomes with restriction endonucleases.
AB  - The viral DNAs from nine wild-type insect baculoviruses have been isolated and
      the EcoR-1 restriction endonuclease fragment patterns compared. Genomic
      heterogeneity could be detected in the DNA restriction patterns of four of these
      wild-type baculoviruses. Three infectious virus forms (two that are occluded in
      the nucleus and an extracellular virus that has budded from the plasma membrane
      of infected cells) of a nuclear polyhedrosis virus with multiple nucleocapsids
      per envelope (MNPV) from the lepidopteran insect, Autographa californica are
      shown to be phenotypically distinct by comparison of viral structural
      polypeptides by polyacrylamide gel electrophoresis and autoradiography of
      L[35S]methio-nine-labeled virus proteins. The three phenotypic forms were cloned
      by successive plaque purification and eight distinct variants were identified
      from 11 plaque-purified viruses by genotypec analysis with EcoR-1 and HindIII
      restriction endonuclease. Isolation of variants from the three phenotypic forms
      has shown that each of the infectious forms is heterogeneous and that no
      segregation of genotypes among the three forms was evident. The characteristic
      restriction fragment patterns of several variants were maintained upon multiple
      passage in cell culture.

PMID- 18627887
TI  - The chemical subunit of tobacco ringspot virus coat protein.
AB  - The coat protein of tobacco ringspot virus (TRSV) dissociated in the presence of
      sodium dodecyl sulphate (SDS), urea, and 2-mercaptoethanol (MCE) separated into
      six components on electrophoresis in polyacrylamide gels. It was established that
      none of the components was a protein of host plant origin and that they were all
      chemically and antigenically similar. The estimated molecular weights of the
      components ranged from about 14,000 to more than 110,000, approximating a
      polymeric series of 1, 2, 3, 4, and 8; over 85% of the protein was recovered in a
      band with a molecular weight of about 57,000. These data, together with the amino
      acid composition of the protein and the results of tryptic peptide mapping
      experiments, indicate that the TRSV capsid is constructed from a single
      polypeptide species containing 119 amino acid residues with a molecular weight of
      12,988. These results are discussed in relation to capsomeric models of the TRSV
      protein shell.

PMID- 18627889
TI  - Two flagellotropic phages and one pilus-specific phage active against
      Asticcacaulis biprosthecum.
AB  - Three phages active against cells of Asticcacaulis biprosthecum attach to
      receptor sites located at the pole of the cell where pili, flagella, and holdfast
      are produced. Phage phiAcS2, a large phage with a prolate cylindrical head and
      flexible, noncontractile tail, attaches to flagella as well as to receptor sites
      at the pole of the cell. Attachment to flagella occurs at the region where head
      and tail of the phage are joined, leaving the distal end of the tail free for
      attachment to receptor sites at the cell surface. Phages phiAcM2 and phiAcM4, are
      identical in appearance to each other, possessing prolate cylindrical heads and
      flexible, noncontractile tails, and are smaller than phage phiAcS2. Phage
      phiAcM4, exhibits the same flagellotropic characteristic as described for phage
      phiAcS2, including the manner of attachment to flagella. Phage phiAcM2 has no
      affinity for flagella, but attaches by the distal end of the tail to pili and to
      receptor sites at the pole of the cell. Mechanical removal of flagella and pili
      protects against infection by all three phages. Studies with phage-resistant
      mutants and with KCN-treated cells suggest that pili are required for infection
      by both flagellotropic and pilus-specific phages.

PMID- 18627890
TI  - Comparative analysis of the enveloped virions of two granulosis viruses of the
      armyworm, Pseudaletia unipuncta.
AB  - The enveloped virions of two strains of a granulosis virus, a synergistic
      Hawaiian (GVH) and a nonsynergistic Oregonian (GVO) strain which infect the
      armyworm, Pseudaletia unipuncta, were liberated from their capsules with 0.02 N
      NaOH and purified by filtration through membrane filters. The envelopes were
      solubilized with 0.1% Triton X-100. The enveloped virions, analyzed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), had 9 to 12
      polypeptides, 3 of which were associated with the naked virion. The two strains
      differed in their electrophoretic patterns mainly in the presence of two heavy
      polypeptides (89,000 and 97,000 daltons) and a 52,000-dalton polypeptide in GVH
      and in the absence of the heavy polypeptides and the presence of a 57,000-dalton
      polypeptide in GVO. The two heavy polypeptides were sensitive to proteinase. Two
      two-dimensional electrophoreses (first dimension with agarose gel electrophoresis
      and second dimension with SDS-PAGE and immunoelectrophoresis) of the envelope of
      GVH resolved two polypeptides, 37,000 and 48,000 daltons, which were
      serologically related to the synergistic factor present in the capsule of GVH;
      however their molecular weights differed from that of the GVH synergistic factor.
      In GVO, no polypeptide serologically related to the synergistic factor was
      detected in the envelope. The enveloped virions purified by differential
      filtration were infectious when fed to armyworm larvae, but the naked virions,
      free of envelopes, were not infectious.

PMID- 18627891
TI  - The stability of satellite viral RNAs in vivo and in vitro.
AB  - Like the satellite RNA (Sat-RNA) of cucumber mosaic virus (CMV), the RNA of
      satellite tobacco necrosis virus (STNV-RNA) was shown to be capable of surviving
      in vivo without replication for at least 10 days in the absence of its helper
      tobacco necrosis virus (TNV). However, under similar conditions, the genomic RNA
      3 of CMV failed to survive for 48 hr. It has been demonstrated that both STNV-RNA
      and Sat-RNA are significantly more resistant to inactivation in vitro than the
      RNAs of their helper viruses. The thermal denaturation kinetics of STNV-RNA and
      Sat-RNA, unlike those of TNV-RNA and CMV-RNA, are more like those of transfer RNA
      (tRNA) indicating that a high proportion of their nucleotides are involved in
      base pairing. STNV-RNA, Sat-RNA, and tRNA also show similar degrees of resistance
      to degradation by the single strand-specific S(1) nuclease. It is suggested that
      both STNV-RNA and Sat-RNA may owe their in vitro stability to features of their
      molecular structure which may also account for their ability to survive in vivo
      for prolonged periods without replication. Similarities and differences between
      satellites and viroids are discussed and it is concluded that these two classes
      of RNAs are unlikely to be related. The possible evolutionary origins of the
      satellites are also considered.

PMID- 18627892
TI  - pH-Dependent urea sensitivity of southern bean mosaic virus.
AB  - The behavior of southern bean mosaic virus (SBMV) virions in urea was markedly pH
      dependent and revealed several novel features. In the absence of urea (5 degrees
      , 1 hr) SBMV was stable as a 115 S entity between pH 2.5 and 9.5, yielded a
      slowly sedimenting (ca 60-65 S) entity at pH 10.5, and was degraded into a 35-40
      S product at pH 11.0. In 4.0 M urea, SBMV was precipitated irreversibly at pH 2.5
      or 10.0, yielded variously sedimenting aggregates at pH 3.0, was transformed
      progressively into a 80 S entity between pH 7.0 and 9.5, or remained structurally
      intact at pH 3.5 to 6.5. In 8.O M urea, SBMV was precipitated at pH 3.5 and below
      or pH 7.5 and above, showed a tendency for the particle:particle interaction at
      pH 6.5 and 7.0, but remained stable between pH 4.0 and 6.0. Under conditions
      where SBMV was somewhat destabilized with urea, increase in the temperature or
      ionic concentration caused virion precipitation without any detectable
      degradation. SBMV was dissociated with 4.0 or 8.0 M urea at pH 5.5 but only in
      the presence of 1.0 M NaCl and at the elevated temperatures (>50 degrees ). These
      results on the rather unusual SBMV behavior in urea, as compared to other
      viruses, are discussed in relation to the available information on the SBMV
      stabilizing interactions.

PMID- 18627893
TI  - Cytopathological evidence for the division of barley yellow dwarf virus isolates
      into two subgroups.
AB  - The cytological survey of oat cells in tissue infected with different aphid
      specific or aphid-nonspecific isolates of barley yellow dwarf virus (BYDV) was
      concluded in this study with the examination of the alterations induced by
      Schizaphis graminum-specific and S. graminum-nonspecific isolates. Cytological
      alterations were similar with all four isolates examined, except that
      proliferated membranous inclusions, common with three of the isolates, were
      absent with S. graminum-nonspecific isolate 6712. Isometric virus-like particles,
      slender filaments, and single-membraned vesicles containing densely staining
      fibrils occurred in the cytoplasm with all the isolates. Nuclear alterations
      consisted of distortion of the outline of the nucleus, followed by aggregation
      and accumulation of densely staining material within the nucleus. The
      cytopathological alterations observed in cells infected with isolate 6712 were
      similar to those found previously with aphid-nonspecific isolates transmitted
      most efficiently by Rhopalosiphum padi-, and Macrosiphum avenae-specific isolates
      of BYDV, while the other three isolates differed in the presence of the
      proliferated, membranous inclusions. Evidence from cytopathology indicates that
      the six known aphid-specific or nonspecific variants of BYDV may be categorized
      into two subsections. The general agreement of the cytopathological evidence,
      with that from serological and cross-protection studies is discussed.

PMID- 18627894
TI  - Specificity of in vitro reconstitution of bromegrass mosaic virus.
AB  - Bromegrass mosaic virus (BMV) RNA was allowed to compete with yeast tRNA or
      alfalfa mosaic virus (AMV) RNA for in vitro encapsidation by BMV protein. Various
      proportions of 32P-labeled foreign RNAs were added to a reassembly mixture (BMV
      protein: BMV RNA, 4:1) and the reassembly products were observed by analytical
      and rate-zonal sedimentation, and the RNA contents of the nucleocapsids were
      examined by gel electrophoresis. Incubation of BMV protein with tRNA alone
      produced 56 S particles containing five or six tRNA molecules per particle, but
      with both tRNA and BMV RNA present very little of the tRNA was incorporated. AMV
      12 S RNA led to 64 S particles containing one AMV RNA molecule: with both AMV and
      BMV RNAs present, the smallest BMV RNA outcompeted the AMV RNA about fourfold,
      even though the two RNAs have similar molecular weights and biological functions.
      Evidently BMV protein does to some extent specifically recognise its own RNA
      molecules.

PMID- 18627895
TI  - Replication of cowpea mosaic virus in protoplasts isolated from immune lines of
      cowpeas.
AB  - In previous work, some lines from a collection of cowpeas (Vigna unguiculata,
      Walp.) were found to be immune to a cowpea mosaic virus strain (CPMV-SB) under
      specified conditions. At 24 hr after inoculation, protoplasts from a susceptible
      and most immune lines were sources of similar amounts of virus, but very little
      virus was recovered from protoplasts of line Arlington. Now we have compared the
      responses of Arlington, several other immune lines, a local lesion host (a
      selection out of the cowpea cross Chinese red x Iron), and a systemic host
      (Blackeye 5) after inoculation under a variety of conditions and by means of
      three types of virus assay. Replication of CPMV-SB apparently did occur in
      Arlington protoplasts, though to a low level only. For lines other than
      Arlington, in vitro inoculation of protoplasts initiated similar "growth curves"
      except that the onset of virus increase was delayed in some. Contrasting results
      were obtained with protoplasts isolated from leaves that had been heavily
      inoculated with CPMV-SB. The hypersensitivity of Chinese red x Iron seedlings
      then seemed to influence virus replication in the isolated protoplasts; little or
      no virus could be recovered from the protoplasts of the mechanically inoculated
      primary leaves of immune lines. Seedlings of the immune lines also were immune or
      highly resistant to graft inoculation. The results have implications regarding
      general mechanisms of immunity to CPMV-SB and indicate that immunity in this
      system is not an exaggerated form of hypersensitivity.

PMID- 18627896
TI  - The presence of a cap structure at the 5'-end of barley stripe mosaic virus RNA.
AB  - About 70% of the molecules in the total RNA preparation isolated from barley
      stripe mosaic virus (BSMV, Norwich strain) were capped, i.e., contained a 5'
      terminal inverted 7-methylguanosine. At least two individual components of the
      genomic RNA (RNA 1 and RNA 3) were capped. Thus the RNA components of BSMV
      contain both a 3'-poly(A) sequence (A. A. Agranovsky et al., Virology91, 95-105,
      1978) and a 5'-terminal cap.

PMID- 18627897
TI  - Infectivity of partially encapsidated tobacco mosaic virus RNA.
AB  - Tobacco mosaic virus was reconstituted in vitro, and the infectivity of
      intermediate products at various stages of reconstitution was investigated in
      relation to their rod length. The infectivity of intermediates was exponentially
      related to their rod length throughout the reconstitution process, indicating
      that no particular region of TMV-RNA is preferentially susceptible to
      inactivation or more important for infection.

PMID- 18627898
TI  - Inducible bacteriophages of Bacillus licheniformis ATCC 10716.
AB  - Two inducible phages, LP52 and DLP 10716, were isolated from Bacillus
      licheniformis ATCC 10716. Molecular weights of DNAs of LP52 and DLP 10716 are
      38.7 x 10(6) and 8.1 x 10(6), respectively. Restriction endonuclease EcoRI
      digested LP52 DNA and DLP 10716 DNA, yielding 15 discrete bands and no bands on
      agarose gel, respectively. These results suggest that DNA molecules of LP52 are
      homogeneous, while DNA molecules of DLP 10716 are heterogeneous.

PMID- 18627899
TI  - Comparative studies on two satellite RNAs of cucumber mosaic virus.
AB  - Cucumber mosaic virus (CMV) satellite RNA (Sat-RNA, D. W. Mossop and R. I. B.
      Francki, 1978, Virology86, 562-566) is similar in many of its physical and
      biological properties to CMV associated RNA 5 (CARNA 5) described by Kaper and
      Tousignant (1977, Virology85, 323-327). However, CARNA 5, unlike Sat-RNA, causes
      a serious necrotic disease of tomato. Sat-RNA when inoculated together with
      various CMV or tomato aspermy virus strains not only failed to increase the
      severity of symptoms in infected tomato plants, but ameliorated them in some
      instances. Comparisons of the two RNAs by hybridization analysis using 32P
      labelled complementary DNA probes, indicate that they have partial nucleotide
      sequence homology. It is suggested that the difference in their primary structure
      is reflected in their biological properties.

PMID- 18627900
TI  - Structure of the antigen from Fiji disease virus particles eliciting antibodies
      specific to double-stranded polyribonucleotides.
AB  - Antisera with Fiji disease virus (FDV) protein-specific and double-stranded (ds)
      RNA-specific antibodies were prepared by injecting rabbits with highly purified
      preparations of FDV cores. Electron microscopic examination of negatively stained
      core preparations disclosed the presence of icosahedral particles, about 54 nm in
      diameter, with projections (B spikes) at their vertices as previously reported.
      However, observations on similar preparations by electron microscopy of specimens
      shadowed at a low angle, by immune electron microscopy and by examination of thin
      sections of pelleted material, established that the particles consisted of cores
      to which some ds RNA strands were attached externally. The relationship of FDV
      core structure to its immunogenic properties is discussed.

PMID- 18627901
TI  - Specificity among barley yellow dwarf viruses in enzyme immunosorbent assays.
AB  - Parallel homologous and heterologous enzyme-linked immunosorbent assays revealed
      a marked homologous specificity among four isolates of barley yellow dwarf virus
      (BYDV). Relatively weak heterologous reactions permitted division of the viruses
      into two groups. The RPV and RMV isolates have some common antigens, but appear
      to be unrelated to the MAV and PAV isolates, which are related to each other. A
      fifth BYDV isolate, SGV, did not react strongly with any of the four virus
      specific globulins studied, but faint reactions suggested a relationship with
      PAV.

PMID- 18627902
TI  - Characteristics of the DNA from Lymantria dispar nuclear polyhedrosis virus.
AB  - The DNA isolated from occluded Lymantria dispar nuclear polyhedrosis virus
      consisted of double-stranded linear, open circular, and covalently closed
      molecules. The DNA had a guanosine plus cytosine content (G + C) of 59-62% as
      estimated from both thermal denaturation and CsCl density gradient
      centrifugation. The L. dispar host DNA had a G + C content of 38-39%. Comparisons
      of molecular weight estimations for viral DNA by sedimentation on neutral sucrose
      gradients, electron microscopy, and reassociation kinetics gave values of 91-106
      x 10(6), 94-102 x 10(6), and 78-93 x 10(6), respectively. Preliminary analysis of
      restriction endonuclease profiles indicated a molecular weight of approximately
      88 x 10(6) for the sum of the fragments.

PMID- 18627903
TI  - Immune effects of mesenchymal stem cells: implications for Charcot-Marie-Tooth
      disease.
AB  - Mesenchymal stem cell (MSC) therapy is the most clinically advanced form of cell
      therapy, second to hematopoietic stem cell transplants. To date, MSC have been
      used for immune modulation in conditions such as Graft Versus Host Disease (GVHD)
      and Crohn's Disease, for which Phase III clinical trials are currently in
      progress. Here, we review the immunological properties of MSC and make a case for
      their use in treatment of Charcot-Marie-Tooth disease type 1 (CMT1), a group of
      inherited peripheral neuropathies. CMT1 is characterized by demyelination and
      aberrant immune activation making this condition an ideal target for exploration
      of MSC therapy, given the ability of these cells to promote sheath regeneration
      as well as suppress inflammation. Studies supporting this hypothesis will be
      presented and placed into the context of other cell-based approaches that are
      theoretically feasible. Given that MSCs selectively home to areas of
      inflammation, as well as exert effects in an allogeneic manner, the possibility
      of an "off the shelf" therapy for CMT1 will be discussed.

PMID- 18627904
TI  - Spatial patterns of polybrominated diphenyl ethers (PBDEs) in mosses, herbivores
      and a carnivore from the Norwegian terrestrial biota.
AB  - The widespread occurrence of polybrominated diphenyl ethers (PBDEs) in the
      environment has attracted considerable attention, leading to concerns about the
      extent and magnitude of wildlife and human exposure. In this work, we focus on
      the occurrence and fate of PBDEs in a Norwegian air-plant-herbivore-carnivore
      system. Specifically, we have analysed for PBDEs in moss, livers from various
      terrestrial herbivores (moose, grouse, and European roe deer) and, for the first
      time, livers from the top predator lynx. The samples were collected from
      different sites and time periods (1990-2004) to identify possible spatial and
      temporal trends in contaminant levels and patterns. The general finding was that
      PBDEs were found in all (biotic) samples, although at lower concentrations than
      previously observed in mammals from the marine environment. The PBDE levels in
      the herbivores ranged from less than 0.5 ng/g lipid weight to 9.4 ng/g lipid
      weight as the highest. The median PBDE concentration in lynx was approximately
      one order of magnitude higher than in the herbivores. In the lynx samples there
      was a predominance of BDE-153 whereas BDE-47 and 99 dominated in the herbivores.
      This probably reflects different bioaccumulation properties or metabolic
      transformation processes of the BDE-congeners, and food choice. Levels of PBDEs
      in both moss and herbivores showed a general decline towards the northern parts
      of Norway. No clear temporal trends were observed. The PBDE levels observed in
      this study were low and are probably of limited toxicological significance.

PMID- 18627905
TI  - Carbonic anhydrase activators: Activation of the human cytosolic isozyme III and
      membrane-associated isoform IV with amino acids and amines.
AB  - An activation study of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms
      hCA III (cytosolic) and IV (membrane-associated) with a series of natural and non
      natural amino acids and aromatic/heterocyclic amines is reported. hCA III was
      efficiently activated by d-His, serotonin, pyridyl-alkylamines, and aminoethyl
      piperazine/morpholine (K(A)s of 91nM-1.12microM), whereas the best hCA IV
      activators were 4-amino-phenylalanine, serotonin, and 4-(2-aminoethyl)-morpholine
      (K(A)s of 79nM-3.14microM). Precise steric and electronic requirements are needed
      to be present in the molecules of effective CA III/IV activators, in order to
      assure an adequate fit within the enzyme active site for the formation of the
      enzyme-activator complex, and for efficient proton transfer processes between the
      active site and the reaction medium. The activation profiles of CA III and IV are
      distinct from those of all other mammalian CA isoforms investigated so far for
      their interaction with amino acids and amines.

PMID- 18628064
TI  - Research in oncology: legal and ethical aspects.

PMID- 18628065
TI  - Metal that came from the sky.

PMID- 18628066
TI  - Molecular biology of retinoblastoma.
AB  - Retinoblastoma (Rb), the most common intraocular tumor in childhood, is caused by
      the loss of function of both retinoblastoma susceptibility gene (RB1 or Rb1)
      alleles. In 1971, Alfred Knudson proposed his "two-hit" theory based upon empiric
      observations of the clinical genetics of Rb, revealing the role of tumor
      suppressor genes in human cancer. Knudson proposed that: "In the dominant
      inherited form of Rb, one mutation is inherited via germ line and the second
      occurs in somatic cells. In the nonhereditary form, both mutations occur in
      somatic cells." The Knudson hypothesis was validated later with the cloning of
      RB1, the first tumor-suppressor gene to be identified. A few years later, Harbour
      extended these findings to small-cell lung cancer, showing that the RB1 locus was
      disrupted in tumors other than Rb and osteosarcoma. Since then, it has been found
      that most, if not all, tumors have defects in their RB1 pathway through genetic
      lesions in the RB1 gene itself or other genes in the pathway. The history of Rb
      research highlights how basic research on a rare childhood cancer can have a much
      broader effect on a disease that affects millions of people each year worldwide.

PMID- 18628067
TI  - Histone deacetylase inhibitors: mechanism of action and therapeutic use in
      cancer.
AB  - Histone deacetylases (HDACs) remove the acetyl groups of lysine residues of
      histone tails leading to chromatin compaction and transcriptional repression. In
      addition, HDACs can also influence transcription-independent events such as
      mitosis or deoxyribonucleic acid (DNA) repair and deacetylate nonhistone proteins
      involved in cell proliferation and death, altering their function. Histone
      deacetylase inhibitors (HDACi) constitute a promising treatment for cancer
      therapy due to their low toxicity. HDACi have been shown to induce
      differentiation, cell-cycle arrest, and apoptosis and to inhibit migration,
      invasion, and angiogenesis in many cancer cell lines. In addition, these
      compounds inhibit tumor growth in animal models and show antitumor activity in
      patients. HDACi alone and in combination with a variety of anticancer drugs are
      being tested in clinical trials, showing significant anticancer activity both in
      hematological and solid tumors. SAHA (vorinostat, Zolinza) was the first HDACi
      approved by the US Food and Drug Administration to enter the clinical oncology
      market for treating cutaneous T-cell lymphoma (CTCL) and is being tested for
      other malignancies.

PMID- 18628068
TI  - Circulating tumor cells in breast cancer: methodology and clinical repercussions.
AB  - Breast cancer is the most common type of cancer among women, and clinicians have
      long recognized its heterogeneity. Its detection and treatment in early stages
      allow for reduction of mortality. Despite the advances and new strategies for
      combining surgical, radiotherapy, and chemotherapy options, however, the
      percentage of patients developing metastases and advanced stages remains high.
      Even though serum tumor markers have been used for the early diagnosis of
      metastases, their systematic determination has not had an effect on survival.
      Methods that are more reliable are needed to detect metastases earlier than with
      the common clinical methods and thus start treatment before overt relapse. Early
      indicators of response or resistance to treatment are also an issue in clinical
      practice. Imaging techniques are time consuming, and it is difficult to detect
      changes that indicate response limited to therapy, and approaches to defining
      changes in tumor mass are time and resource consuming. In contrast, detection of
      circulating tumor cells (CTC) could be a useful tool in early detection of
      relapse and response to systemic chemotherapy. Extremely sensitive techniques are
      available that are easily applied to peripheral blood samples, which might
      provide enormous research possibilities in this area.

PMID- 18628069
TI  - Clinical application of intensity-modulated radiotherapy for head and neck
      cancer.
AB  - Intensity-modulated radiotherapy (IMRT) is a modern treatment technique that
      allows one to shape the dose to the target volume and to reduce the dose
      delivered to healthy tissue. Over the last decade, IMRT has been implemented for
      head and neck cancer treatment, with the aim of reducing the dose delivered to
      the parotid glands and improving the dose coverage of complex target volumes
      located close to critical structures. The potential benefits of IMRT in terms of
      salivary function preservation and better local control have contributed to the
      rapid diffusion of this new technology. However, it should not be overlooked that
      IMRT is a novel treatment technique and that its clinical application represents
      a paradigm shift in the practice of radiation oncology. The purpose of this
      article is to review the clinical experience with IMRT for head and neck cancer
      treatment and to discuss some important issues related to its implementation.

PMID- 18628070
TI  - High-dose-rate intensity modulated brachytherapy with external-beam radiotherapy
      improves local and biochemical control in patients with high-risk prostate
      cancer.
AB  - Purpose Our aim was to report the 8-year outcome of local dose escalation using
      high-dose-rate conformal brachytherapy combined with external irradiation for
      patients with high-risk prostate cancer. Material and methods From June 1998 to
      June 2007, 134 patients with high-risk localized prostate cancer were
      prospectively enrolled in the study. The median follow-up was 45 months (12-107).
      Only patients considered as having high-risk criteria were accepted [prostate
      specific antigen (PSA) > or =20 ng/ml and/or Gleason >7 and/or stage > or =T3a or
      two intermediate-risk criteria: PSA 11-19 ng/ml, Gleason 7, stage T2b-c]. The
      total dose applied by external beam radiotherapy was 46 Gy in 200-cGy daily
      fractions. High-dose-rate brachytherapy was performed at the end of weeks 1 and 3
      of the 5-week radiotherapy course. The doses administered in each application was
      1,150 cGy. Any patient free of clinical or biochemical evidence of disease was
      termed b-NED. Actuarial rates of outcome were calculated by Kaplan. Meier
      analysis and compared using the log-rank test. Cox regression models were used to
      establish prognostic factors of the measures of outcome. Results Mean follow-up
      for the entire group was 45 months (range 12-107). The overall survival (OS)
      according to Kaplan-Meier estimates was 85% (+/-5) at 5 and 8 years. The 5 and 8
      years for biochemical control were 80% (+/-4%) and 73% (+/-7%), respectively,
      whereas for failure in tumor-free survival (TFS), they were 82% (+/-3) at 5 and 8
      years, respectively. The 8-year cause-specific mortality was 10% (+/-4%). The
      multivariate Cox regression analyses identified the number of poor prognostic
      factors as independent for biochemical failure. Our report includes only patients
      considered as high risk, and the 8-year b-NED survival rate was 83% for patients
      with two intermediate-risk criteria, 78% for patients with one poor prognostic
      factor, 56% for two and 35% for all three (p = 0.001). There were no urethral
      strictures and/or urinary incontinence. Gastrointestinal toxicity grade 2 was
      7.5%. Conclusions The 8-year results confirm the feasibility and effectiveness of
      external-beam radiation therapy with conformal high-dose-rate brachytherapy boost
      for patients with high-risk tumor. The late toxicity rates were low,
      corroborating the excellent dose conformity.

PMID- 18628071
TI  - Could other viruses cause pediatric posttransplant lymphoproliferative disorder?
AB  - INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) constitutes a
      heterogeneous group of diseases. We summarize the experience of our hospital, one
      of Spain's largest series of renal (294), liver (47) and allogeneic stem cell
      transplants (67), where four cases of PTLD have developed related to complex
      viral infections. METHODS: Case 1 was a 24-month-old boy diagnosed with acute
      lymphoblastic leukemia who underwent allogeneic stem-cell transplantation (SCT).
      He was seropositive for Epstein-Barr virus (EBV) and developed an aggressive
      Bcell non-Hodgkin's lymphoma (B-NHL) related to EBV reactivation and human
      herpesvirus 6 (HHV-6) infection. Cases 2, 3, and 4 developed after kidney
      transplantation and were all EBV seronegative. Case 2 had associated
      cytomegalovirus (CMV) and EBV infection. Cases 3 and 4 only revealed EBV viral
      load. Cases 1, 3, and 4 progressed rapidly, with fatal outcome. Global incidence
      of PTLD in our series is 1.1%. CONCLUSION: PTLD is a rare but life-threatening
      condition. Although EBV plays a clear role in its pathogenesis, other associated
      viral infections could trigger this situation. Current therapies include
      rituximab, decreasing immunosuppressive drugs. and conventional chemotherapy.

PMID- 18628072
TI  - Impact of erythropoietin on the reduction of blood transfusions and on survival
      of lung cancer patients receiving first-line chemotherapy.
AB  - INTRODUCTION: Anaemia is a common problem in patients with cancer who receive
      chemotherapy and is normally associated with a negative impact on patients'
      quality of life (QOL), poor cancer control and diminished survival. In clinical
      trials, recombinant human erythropoietin has been shown to correct and prevent
      anaemia, decrease the need for blood transfusions and improve cancer patients'
      QOL. METHODS: A retrospective study followed lung cancer patients who received
      first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of
      anaemia was analysed, as was the impact of incorporating erythropoietin into the
      treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported
      asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia
      rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3
      (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%,
      intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with
      transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs.
      2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI
      322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients
      with anaemia undergoing chemotherapy. It can possibly avoid the need for
      transfusions without negatively impacting survival.

PMID- 18628073
TI  - The Valencia Programme for Fertility Preservation.
AB  - INTRODUCTION: Fertility preservation needs have increased dramatically in recent
      years due to a rising cancer incidence and also a significant increase in
      survival rates. MATERIALS AND METHODS: We report on 200 women participating in
      the Valencia Programme for Fertility Preservation, of whom 55% were breast cancer
      patients, 25% Hodgkin's disease patients, and the remaining 20% suffered from
      other nonmalignant and malignant diseases. Mean age was 28.2 years (11-39).
      Before patients were submitted to oncological treatment, the right ovarian cortex
      was extracted by laparoscopy and cryopreserved. Once the patient was free of
      disease, the right ovarian cortex was thawed and implanted onto the left ovarian
      medulla (after extraction at the same surgical time of left ovarian cortex).
      RESULTS: In 95% of cases, a piece approximately 2 x 3 cm was obtained. The
      procedure did not cause any change in the cancer therapy schedule. Four implants
      had been performed (all of them in women who underwent chemotherapy prior to
      ovarian cortex extraction), from which two of the case achieved ovarian function
      resumption, in one case a month after the implant and in the other 5.5 months
      after. The remaining two implanted cases were performed 5 and 6 months prior to
      the writing of this paper, respectively. CONCLUSIONS: Ovarian tissue
      cryopreservation is a feasible option to preserve ovarian function and possibly
      fertility in adolescents and young women at risk of developing premature ovarian
      failure (POF) due to chemotherapy and/or radiotherapy.

PMID- 18628074
TI  - Hodgkin's disease and intercurrent processes that may simulate a relapse.
AB  - Hodgkin's disease (HD) is an example of a curable disease. In addition, it can
      serve as a lesson about other pathologies because of the delayed side effects it
      produces and the appearance of associated processes that may simulate disease
      progression. Here we provide a case report of a patient who encapsulates a
      compendium of situations that may occur in HD.

PMID- 18628075
TI  - A novel EGFR nonsense mutation in a non-small-cell lung cancer (NSCLC) patient
      who did not derive any clinical benefit with combination chemotherapy and
      erlotinib.
AB  - Most of the somatic epidermal growth factor receptor (EGFR) mutations described
      to date in non-smallcell lung cancer (NSCLC) patients are located in the kinase
      domain and are considered activating mutations. Some of these mutations are
      associated with response to specific EGFR tyrosine kinase inhibitors (TKI) such
      as gefitinib and erlotinib. Here we report a case of a previously undescribed
      EGFR nonsense mutation in a lung adenocarcinoma patient who did not derive any
      clinical benefit with combination chemotherapy and erlotinib. To the best of our
      knowledge this is the second report in the literature describing an EGFR nonsense
      mutation in lung cancer patients.

PMID- 18628076
TI  - Clinical case report and literature review: metachronous colorectal splenic
      metastases.
AB  - A 52-year-old woman with a rising carcinoembryonic antigen CEA, no clinical or
      radiological findings, a negative colonoscopy, and a positron emission tomography
      (PET) scan that revealed an isolated hypermetabolic lesion in the spleen. The
      patient underwent splenectomy by laparoscopic surgery. The pathological study
      confirmed the presence of an isolated metastasis to the spleen. This case reveals
      the rare occurrence of isolated splenic metastases in the context of colorectal
      cancer and illustrates the role of PET when a patient shows a rising CEA with
      negative clinicoradiological studies.

PMID- 18628077
TI  - Pathologic spectrum and lung dust burden in giant cell interstitial pneumonia
      (hard metal disease/cobalt pneumonitis): review of 100 cases.
AB  - Hard metal disease (HMD), the interstitial lung disease caused by dusts in the
      cemented tungsten carbide (WC) industry, has been attributed to cobalt. The rare
      histologic pattern of giant cell interstitial pneumonia (GIP) is characteristic
      in HMD. The authors reviewed the history of HMD and 100 cases of HMD that they
      have seen over 5 decades. GIP was proven in 59; analysis of the lung inorganic
      particle burden by scanning electron microscopy and energy-dispersive x-ray
      spectroscopy confirmed HMD in the other 41. Cases have been diagnosed by
      bronchoalveolar lavage, lung biopsy, and autopsy. Histopathology findings range
      from focal peribronchiolar inflammation to diffuse interstitial fibrosis and
      honeycombing. GIP cases in the WC industry reveal elevated concentrations of
      tungsten in all, but cobalt was detected in only 6 ( approximately 10%). Of the
      746 diverse cases in the authors' analytical database, almost all cases with the
      highest tungsten concentration showed GIP. This study confirms that GIP is
      effectively pathognomonic for HMD.

PMID- 18628078
TI  - Orally ingested chrysotile asbestos affects rat lungs and pleura.
AB  - The authors designed this study to show the effects of orally ingested asbestos
      on the lungs and pleura. They designated 3 groups of rats: group A (n = 18) was
      given 1.5 g/L asbestos in water, group B (n = 18) was given 3 g/L asbestos in
      water, and group C (n = 15), as a control group, was given only water.
      Histopathological evaluation of lungs and pleura of the rats after 6 months
      revealed significant mesothelial proliferation and asbestos bodies. After 9
      months, more rats exhibited mesothelial proliferation in group B than in group A
      (p < .05). The number of rats with asbestos bodies in their lungs was greater in
      group B than in group A. More rats in group B than in group A had asbestos in
      their spleen. The authors observed mesothelial proliferation in all group B rats
      at the end of 12 months. Ingested asbestos traveled from the gastrointestinal
      system to the lungs, likely via a lymphohematological route, leading to
      mesothelial proliferation, which may lead to malignancies.

PMID- 18628079
TI  - Prevalence of respiratory symptoms among sisal processors in Tanzania.
AB  - Respiratory health among sisal workers has been an unresolved issue of concern
      for many years. The authors performed a 1-week follow-up questionnaire study on
      acute respiratory symptoms and cross-shift peak expiratory flows among 163 sisal
      brushing and decortication workers (exposed participants) and 31 security workers
      (control participants) from 6 sisal estates in Tanzania. The authors used the
      Optimal Symptom Score Questionnaire on Acute Respiratory Symptoms and the
      standardized American Thoracic Society and British Medical Research Council
      respiratory questionnaires. Decortication and brushing workers had a higher
      prevalence and higher severity scores of acute symptoms throughout the week than
      did control participants. Shortness of breath among brushing workers decreased (p
      < .01) from 39% on Monday to 20% on Friday. Brushing workers also had
      significantly higher prevalence of chronic sputum (30%) and chest tightness (48%)
      and the lowest preshift and postshift PEF values. The authors recommend
      preventive measures and further research.

PMID- 18628080
TI  - Effects of industrial pollution on respiratory morbidity among female residents
      of India.
AB  - The authors evaluated the respiratory symptoms and pulmonary function test
      results (forced vital capacity [FVC], forced expiratory volume in 1 second
      [FEV1], and ratio of FEV1 to FVC [FEV1%]) of female residents of the critically
      polluted industrial estate of Vapi, Gujarat (state), India, and compared these
      with control information derived from a village 20 km away. The authors
      categorized the studied residents as living in Vapi, in town, or in villages
      proximal to the Gujarat Industrial Development Corporation; living 2 to 3 km away
      from Vapi; living 3 to 5 km away from Vapi; and being in the control group. The
      authors found no significant association between respiratory symptoms and
      pulmonary function among Vapi residents. However, the obstructive type of
      abnormality was most predominant and significantly different among Vapi
      residents. The restrictive type was highly prevalent among residents living 2 to
      3 km away from Vapi compared with the control group. These results suggest
      significant respiratory morbidity among residents that was associated with age
      and distance from the development corporation.

PMID- 18628081
TI  - Miscellaneous occupational lung diseases.
AB  - A case is presented of a rare occupational lung disease for which the workplace
      etiology may have been overlooked. The authors review 4 such diseases, which are
      important to recognize not only because cessation of exposure can lead to
      clinical improvement, but also because other cases of these conditions may be
      identified in the workplace.

PMID- 18628082
TI  - Uncovering clinically relevant phenotypic variations in malignancies: CD23 in
      mantle cell lymphoma.

PMID- 18628083
TI  - Laboratory management of CIN 2: the consensus is consensus.

PMID- 18628084
TI  - CD23+ mantle cell lymphoma: a clinical pathologic entity associated with superior
      outcome compared with CD23- disease.
AB  - Mantle cell lymphoma (MCL) commonly lacks expression of CD23. However, a
      significant minority of MCLs express CD23, as assessed by flow cytometric
      immunophenotyping (FCIP). The aims of our study were to investigate the
      expression of CD23 by FCIP in patients with MCL and to correlate CD23 expression
      with pathologic and clinical parameters, including outcome. We studied 53
      patients with untreated MCL who had CD23 expression determined by FCIP. At
      diagnosis, 14 MCLs (26%) were CD23+ at all tissue sites, whereas 33 (62%) were
      CD23-, and 6 (11%) had discordant CD23 expression among different tissue sites.
      Patients with CD23- MCL had extranodal disease more commonly compared with
      patients with CD23+ MCL. Moreover, with 57-month median follow-up, the 4-year
      event-free and overall survival rates for CD23+ MCL were 45% and 75%,
      respectively, compared with 19% and 51% for CD23- MCL. In multivariate Cox
      regression analysis, CD23 status and leukemic-phase MCL were the most important
      factors predicting outcome.

PMID- 18628085
TI  - Incidence of TCR and TCL1 gene translocations and isochromosome 7q in peripheral
      T-cell lymphomas using fluorescence in situ hybridization.
AB  - Translocations involving the T-cell receptor (TCR) and TCL1 genes occur in T-cell
      precursor lymphoblastic leukemia/lymphoma and prolymphocytic leukemia;
      isochromosome 7q has been associated with hepatosplenic T-cell lymphoma. However,
      the incidence of these abnormalities in peripheral T-cell lymphomas (PTCLs) as a
      whole has not been well defined. We studied genetic abnormalities in 124 PTCLs
      seen at the Mayo Clinic, Rochester, MN, between 1987 and 2007. Tissue microarrays
      were screened using 2-color break-apart fluorescence in situ hybridization probes
      flanking the TCRalpha (TCRA, 14q11), TCRbeta (TCRB, 7q35), and TCRgamma (TCRG,
      7p15) genes and the TCL1 gene (14q32). Isochromosome 7q was analyzed by using a 2
      color probe to 7p and 7q32.1. Translocations involved TCRA in 3 (2.9%) of 102
      cases and TCRB in 1 (1%) of 88. Isochromosome 7q was detected in 2 cases of
      extranodal NK/T-cell lymphoma, nasal type, and 2 cases of anaplastic lymphoma
      kinase-negative anaplastic large cell lymphoma. One of the latter cases also had
      a translocation of TCRA, and further studies confirmed a novel t(5;14)
      translocation.

PMID- 18628086
TI  - Viral studies in burkitt lymphoma: association with Epstein-Barr virus but not
      HHV-8.
AB  - Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma, composed of a
      monomorphic population of medium-sized B cells with a high proliferation rate and
      a consistent MYC translocation. Epstein-Barr virus (EBV) has been associated with
      BL with different frequencies depending on the clinical variant. Kaposi sarcoma
      associated herpesvirus, or human herpesvirus 8 (HHV-8), infects a wide range of
      normal cells, having a well-established role in the pathogenesis of various
      neoplasms, including Kaposi sarcoma, primary effusion lymphoma, multicentric
      Castleman disease (MCD) and MCD-associated plasmablastic lymphoma. In secondary
      immunodeficiencies, such as HIV-1 infection and organ transplantation, HHV-8 is
      considered an opportunistic pathogen linked to the development of lymphomas in
      patients with AIDS and HIV + patients. We studied the association of EBV and HHV
      8 by immunohistochemical analysis, in situ hybridization, and polymerase chain
      reaction in a large number of well-characterized BLs. EBV was present in 45.0% of
      all BL cases with higher incidence in the pediatric group; most cases were EBV
      type A. We found no association of BL with HHV-8 in EBV + BL or in EBV-cases,
      including the HIV + BL group.

PMID- 18628087
TI  - The spectrum of B-cell non-Hodgkin lymphomas with dual IgH-BCL2 and BCL6
      translocations.
AB  - Dual IgH/BCL2 and BCL6 translocations are rarely observed in B-cell non-Hodgkin
      lymphomas (B-NHLs). We investigated the morphologic, phenotypic, and cytogenetic
      spectrum of B-NHL with such dual translocations. Dual IgH/BCL2 and BCL6
      translocations were detected in follicular lymphomas (FLs) and diffuse large B
      cell lymphomas (DLBCLs), representing 6.1% of 132 B-NHLs in our series, including
      6 (11%) of 56 FLs (grades 1, 2, and 3a) and 2 (3%) of 76 DLBCLs; 33% of FLs with
      dual translocations had variant morphologic features. All dual-translocation FLs
      were CD10+/BCL6+/BCL2+/MUM1-, and the DLBCLs demonstrated "activated" germinal
      center (CD10+/BCL6+/MUM1+) and non-germinal center (CD10-/BCL6+/MUM1+)
      phenotypes. BCL6 translocations in all cases involved nonimmunoglobulin
      genes/loci. Mean chromosome abnormalities in dual-translocation FLs and DLBCLs
      did not differ from IgH/BCL2 FLs and DLBCLs. Detection of dual translocations
      predominantly in low-grade FLs suggests that BCL6 abnormalities are acquired
      early in the histologic evolution of a subset of IgH/BCL2-associated FLs.

PMID- 18628088
TI  - Evaluation of the use of monoclonal antibodies and nested PCR for noninvasive
      prenatal diagnosis of hemoglobinopathies in India.
AB  - Our purpose was to develop and evaluate isolation and enrichment of fetal
      erythroblasts and a nested polymerase chain reaction (PCR) approach using fetal
      erythroblasts for detecting the beta-globin gene mutations for a noninvasive
      prenatal diagnosis of hemoglobinopathies. Maternal blood at different periods of
      gestation was layered on a Percoll density gradient for enrichment of fetal
      nucleated RBCs (NRBCs). A combination of 3 monoclonal antibodies (CD45-peridinin
      chlorophyll protein, glycophorin A-phycoerythrin, and anti-hemoglobin F
      fluorescein isothiocyanate) was used for flow cytometric sorting of fetal NRBCs
      from enriched cells. Different nested PCR-based approaches were used for
      identification of fetal mutations. Owing to heterogeneity of beta-thalassemia
      mutations in the population of India, we had to screen for 12 mutations and were
      able to give an accurate diagnosis in 84 (84.0%) of 100 cases when compared with
      chorionic villus sampling or cordocentesis and DNA analysis.This nested PCR
      approach enabled amplification of small quantities of DNA from fetal
      erythroblasts, providing a cost-effective method for noninvasive diagnosis.

PMID- 18628089
TI  - p63 Expression in olfactory neuroblastoma and other small cell tumors of the
      sinonasal tract.
AB  - Olfactory neuroblastoma (ONB) is a rare neoplasm of the head and neck region that
      is included in the differential diagnosis of other sinonasal tract malignancies.
      We studied the usefulness of using p63 as an aid in the diagnosis of ONB and
      other tumors of the sinonasal region. The specimens were 14 ONBs; 4
      nasopharyngeal carcinomas (NPCs), nonkeratinizing subtype; 2 NPCs,
      undifferentiated subtype; 10 sinonasal undifferentiated carcinomas (SNUCs); 7
      malignant melanomas; and 2 extranodal natural killer (NK)/T-cell lymphomas. We
      observed p63 expression in 5 ONBs (36%), 4 nonkeratinizing NPCs (100%), 1
      undifferentiated NPC (50%), 2 SNUCs (20%); 0 malignant melanomas (0%); and 1
      extranodal NK/T-cell lymphoma (50%). While all cases of NPC with positive
      staining for p63 showed strong and diffuse immunoreactivity, the ONB, SNUC, and
      lymphoma cases with positive immunoreactivity showed only focal staining for p63.
      No p63 expression was observed in malignant melanoma. We think p63 is a useful
      marker to help distinguish nonkeratinizing or undifferentiated NPC subtypes from
      various sinonasal tract malignancies. In particular, p63 helps distinguish
      nonkeratinizing and undifferentiated NPC subtypes from SNUC.

PMID- 18628090
TI  - Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma
      on needle biopsy.
AB  - The diagnostic value of glypican 3 (GPC3) immunostaining on needle biopsy
      specimens has not been well assessed. In this study, 120 liver needle biopsy
      specimens, including 46 from cirrhotic livers and 74 hepatocellular carcinomas
      (HCCs), were immunohistochemically examined for expression of GPC3. The results
      showed strong cytoplasmic and membranous staining in 36 HCCs (49%), among which
      20 cases (56%) showed diffuse immunoreactivity. None of the 46 cirrhotic livers
      exhibited positive GPC3 immunostaining. The nonneoplastic liver tissues
      (cirrhotic or noncirrhotic) that were present in the majority of the HCC cases
      were also completely negative for GPC3 expression. These data demonstrate that
      GPC3 is a reliable immunohistochemical marker for the diagnosis of HCC on needle
      biopsy specimens when positive. However, the detection rate in our series seems
      lower than that reported in studies using resection specimens as the study
      materials. Our findings emphasize that GPC3 immunoreactivity can be focal and
      that negative staining should not be viewed as evidence to exclude the diagnosis
      of HCC in challenging needle biopsy specimens.

PMID- 18628091
TI  - Expression of glypican 3 in ovarian and extragonadal germ cell tumors.
AB  - Germ cell tumors (GCTs), rare malignancies that occur in a wide range of
      locations and display variable histologic patterns, may pose diagnostic
      challenges. Glypican 3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has
      been shown to be a novel diagnostic marker in testicular GCT. However, GPC3
      expression in ovarian and extragonadal GCT has not been reported. We evaluated
      GPC3 immunoreactivity in GCTs from 63 patients (57 children and 6 adults),
      including 14 ovarian and 20 extragonadal primary GCTs and 8 metastases along with
      21 primary testicular GCTs for comparison. All 33 yolk sac tumors (YSTs) and both
      choriocarcinomas were immunoreactive for GPC3. In contrast, a minority of
      immature (4/10) and mature (4/35) teratomas were positive. No positivity was seen
      in 6 embryonal carcinomas or 5 germinomas. GPC3 is differentially expressed in
      ovarian and extragonadal GCTs, with expression predominantly observed in YSTs and
      choriocarcinoma.

PMID- 18628092
TI  - Human herpesvirus type 8 in patients with cirrhosis: correlation with sex,
      alcoholism, hepatitis B virus, disease severity, and thrombocytopenia.
AB  - Immunologic abnormalities in patients with cirrhosis strongly correlate with
      severity of liver cirrhosis. The association between cirrhosis and human
      herpesvirus type 8 (HHV-8) infection is unclear. Plasma samples were obtained
      from 74 healthy control subjects and 59 patients with cirrhosis. The seropositive
      rates for HHV-8 antibodies in patients with cirrhosis (25/59 [42%]) were
      significantly higher than that in healthy control subjects (18/74 [24%]; P =
      .027), particularly in men (P = .027), patients with alcohol-related cirrhosis (P
      = .032), and patients with thrombocytopenia (P = .019) or Child-Pugh class C
      cirrhosis (P = .018) or both (P = .015), or hepatitis B virus (HBV) infection (P
      = .003). Antibody titers in seropositive patients also significantly exceeded
      those in healthy control subjects (P = .008). All subjects were negative for anti
      HIV. In Taiwan, cirrhosis is associated with HHV-8 infection, particularly in
      men, patients with Child-Pugh class C cirrhosis and/or thrombocytopenia, and
      patients with alcohol- or HBV-related cirrhosis.

PMID- 18628093
TI  - Amended reports: development and validation of a taxonomy of defects.
AB  - Amended pathology reports produce rework, confusion, and distrust. To develop a
      reproducible amendment taxonomy we derived a classification from 141 amended
      reports, then validated it with 130 new cases before 4 observers independently
      reviewed 430 cases measuring agreement (k). Next, agreement in classifying 30
      other amended reports in 7 institutions was measured. We further tracked
      amendment rates, defect categories, defect discoverers, and discovery mechanisms.
      In the 430-case validation set agreement was excellent (k = 0.8780 [range, 0.8416
      0.9144]). Among the 7 institutions, agreement was good (k = 0.6235 [range, 0.3105
      0.8975]). Amendment rates ranged from 2.6 to 4.8 per 1,000 reports.
      Misinterpretation fractions varied least (23%-29%). Misidentification fractions
      ranged more widely (20%-38%). Specimen defects were least frequent (4%-10%) and
      report defects most frequent (29%-48%). Misidentifications and report defects
      inversely correlated. Pathologists discovered most misinterpretations, and
      clinicians found most misidentifications. Conference review revealed 40% to 80%
      of misinterpretations. This taxonomy produced excellent reproducibility and good
      agreement across institutions.

PMID- 18628094
TI  - High-resolution melting analysis for rapid detection of KRAS, BRAF, and PIK3CA
      gene mutations in colorectal cancer.
AB  - High-resolution melting analysis (HRMA) provides a valid approach to efficiently
      detect DNA genetic and somatic mutations. In this study, HRMA was used for the
      screening of 116 colorectal cancers (CRCs) to detect hot-spot mutations in the
      KRAS and BRAF oncogenes. Mutational hot spots on the PIK3CA gene, exons 9 and 20,
      were also screened. Direct sequencing was used to confirm and characterize HRMA
      results. HRMA revealed abnormal melting profiles in 65 CRCs (56.0%), 16 of them
      harboring mutations in 2 different genes simultaneously. The frequency of
      mutations was 17.2% for PIK3CA (11.2% in exon 9 and 6.0% in exon 20), 43.1% for
      KRAS exon 2, and 9.5% in exon 15 of the BRAF gene. We found a significant
      association between PIK3CA and KRAS mutations (P = .008), whereas KRAS and BRAF
      mutations were mutually exclusive (P = .001). This report describes a novel
      approach for the detection of PIK3CA somatic mutations by HRMA.

PMID- 18628095
TI  - Frequency and clinical significance of simultaneous association of lobular
      neoplasia and columnar cell alterations in breast tissue specimens.
AB  - Lobular neoplasia (LN) and columnar cell alterations (CCAs) may share similar
      genetic abnormalities, but there is no appreciable literature that addresses the
      simultaneous occurrence of these lesions in breast core biopsy (CNB) specimens or
      resection specimens. Three groups of breast tissue were examined: group 1, 68 CNB
      specimens targeted for "suspicious" microcalcifications (Breast Imaging Reporting
      and Data System [BI-RADS] 4) and diagnosed with LN; group 2, 2,516 CNB reports
      for a 1-year period; and group 3, 400 consecutive breast carcinoma resection
      specimens analyzed for LN and CCAs within the vicinity of carcinoma. In group 1,
      LN was associated with CCAs in 54% of cases (37/68). In group 2, LN was found in
      association with CCA in 1.3% of cases (32/2,516). In group 3, 13.0% of cases of
      CCAs (52/400) were associated with LN. Our study suggests the association of
      these two lesions in breast tissue is nonrandom and that they may have a common
      progenitor pathway of neoplastic development.

PMID- 18628096
TI  - Virtual 3D microscopy using multiplane whole slide images in diagnostic
      pathology.
AB  - To reproduce focusing in virtual microscopy, it is necessary to construct 3
      dimensional (3D) virtual slides composed of whole slide images with different
      focuses. As focusing is frequently used for the assessment of Helicobacter pylori
      colonization in diagnostic pathology, we prepared virtual 3D slides with up to 9
      focus planes from 144 gastric biopsy specimens with or without H pylori
      gastritis. The biopsy specimens were diagnosed in a blinded manner by 3
      pathologists according to the updated Sydney classification using conventional
      microscopy, virtual microscopy with a single focus plane, and virtual 3D
      microscopy with 5 and 9 focus planes enabling virtual focusing. Regarding the
      classification of H pylori, we found a positive correlation between the number of
      focus planes used in virtual microscopy and the number of correct diagnoses as
      determined by conventional microscopy. Concerning H pylori positivity, the
      specificity and sensitivity of virtual 3D microscopy using virtual slides with 9
      focus planes achieved a minimum of 0.95 each, which was approximately the same as
      in conventional microscopy. We consider virtual 3D microscopy appropriate for
      primary diagnosis of H pylori gastritis and equivalent to conventional
      microscopy.

PMID- 18628097
TI  - The distinction of bronchogenic cyst from metastatic testicular teratoma: a light
      microscopic and immunohistochemical study.
AB  - Bronchogenic cyst (BC), a rare developmental abnormality of the primitive foregut
      and usually found above the diaphragm, can occur in the retroperitoneum and other
      unusual locations where distinction from metastatic teratoma is essential. We
      studied 22 BCs and 34 teratomas metastatic to the retroperitoneum in men. Of 22
      BCs, 17 (77%) showed well or moderate architectural differentiation toward normal
      tracheobronchial structures, whereas none of the teratomas did. In addition, 20
      (91%) of the BCs had respiratory-type epithelium and none had enteric-type
      epithelium. Immature elements, atypia, and tumor necrosis were absent in BCs. All
      BCs expressed cytokeratin (CK) 7, and none expressed CDX-2 in immunohistochemical
      analysis. Teratomas had mixed enteric and respiratory-type epithelium. The
      majority of the glands were positive for CK7 (33 [97%]), CK20 (34 [100%]), CDX-2
      (34 [100%]), and thyroid transcription factor (TTF)-1 (17 [50%]). Coexpression of
      CDX-2 and TTF-1 was found in 11 teratomas (32%) but none of the BCs. BCs can be
      reliably distinguished from teratomas based on the gross, histologic, and
      immunohistochemical features.

PMID- 18628098
TI  - HER2 overexpression and amplification in urothelial carcinoma of the bladder is
      associated with MYC coamplification in a subset of cases.
AB  - We examined 53 invasive high-grade urothelial carcinomas (UCCs) and 42 paired
      lymph node metastases to determine frequency of HER2 overexpression, HER2/MYC
      coamplification, and association between HER2 and MYC status and
      clinicopathologic features. HER2 overexpression occurred in 19 UCCs (36%) and 14
      metastases (30%), with an 88% concordance rate between UCCs and matched
      metastases. HER2 amplification occurred in 5 (10%) of 50 UCCs and 4 (11%) of 36
      metastases, with a 100% concordance rate; MYC amplification occurred in 7 (18%)
      of 40 UCCs and 4 (13%) of 32 metastases, with a concordance rate of 50% between
      UCCs and metastases. Of 7 cases demonstrating HER2 amplification, MYC was
      coamplified in 4 (57%; P = .01), and coamplification was associated in all cases
      with metastasis and advanced local disease (pT4). Coamplification of HER2 and MYC
      occurs in a subset of patients with metastatic UCC. HER2 overexpression and
      amplification in metastatic lesions suggest that HER2-targeted therapy may be
      valuable for patients undergoing treatment for metastatic UCC, for which current
      therapy is limited. Further studies into the role of MYC coamplification in this
      population are needed to determine impacts on treatment with HER2-targeted
      therapy.

PMID- 18628099
TI  - A single-tube screen for Salmonella and Shigella.
AB  - Salmonella and Shigella species are routinely sought in stool specimens submitted
      for culture. It is a common practice to screen lactose-negative colonies by using
      triple sugar iron agar, lysine iron agar, and Christensen urea agar to determine
      if further identification is necessary. We designed and evaluated a novel
      combination of media, which are layered in a single tube, for screening isolates
      suspected to possibly represent Salmonella or Shigella. We tested this media
      combination with 106 Salmonella, 56 Shigella, and 56 other gram-negative bacilli.
      All Salmonella and Shigella isolates tested were appropriately characterized as
      possible Salmonella or Shigella by using an algorithm developed for use with this
      media combination. Similarly, 53 (95%) of 56 other gram-negative bacilli were
      appropriately screened as non -Salmonella and non -Shigella isolates. This unique
      media combination provides the most important biochemical reactions needed to
      screen for Salmonella and Shigella in a single-tube format, which decreases labor
      by two thirds (ie, 1 tube is inoculated vs 3).

PMID- 18628100
TI  - Application of 3-D Delta check graphs to HbA1c quality control and HbA1c
      utilization.
AB  - Delta checking is a laboratory information system (LIS)-based tool that detects
      patient and laboratory quality control errors. By using hemoglobin A1c (HbA1c)
      data, we developed a novel approach to summarizing and presenting patient Delta
      values to address limitations of current Delta check algorithms. Delta values
      were calculated from intrapatient pairs of HbA1c (n = 55,327) measured during 2
      years in a single referral or a university hospital laboratory. Three-dimensional
      Delta-time (DeltaT) and percentile limit graphs were constructed. Cumulative
      distribution function analysis was used to explore clinical utilization. The
      DeltaT graphs showed that HbA1c Delta values increase asymmetrically over time.
      Although the 2.5 to 97.5 and 5.0 to 95.0 percentile Delta check limits were
      similar for both sites, the referral laboratory's 0.5 to 99.5 percentile limits
      were wider. For acute patient care environments, we recommend limits of -3.5% and
      1.8% for measurements between 0 and 60 days and -4.0% and 2.0% for measurements
      between 60 and 120 days. For the outpatient environment, we recommend limits of 
      4.2% and 2.1% and 5.0% and 2.5% for measurements between 0 and 60 days and 60 and
      120 days, respectively.Delta checking can be significantly improved with
      customization of limits set by population and interobservation period. Because
      LIS systems are incapable of these customizations, customers must become
      advocates for these modifications.

PMID- 18628101
TI  - Potential biomarkers of acute cerebral infarction detected by SELDI-TOF-MS.
AB  - No single biologic marker is used in the routine diagnosis of acute cerebral
      infarction. We screened for potential biomarkers in 92 plasma samples, including
      samples from 32 patients with acute cerebral infarction and 60 hospital control
      subjects. Pretreated plasma samples were analyzed using SELDI-TOF-MS (Ciphergen
      Biosystems, Fremont, CA). Proteomic spectra of mass to charge ratio (m/z) were
      generated by the application of plasma to weak cation exchange (CM10 ProteinChip,
      Ciphergen Biosystems) arrays. A differential pattern consisting of 13 biomarkers
      was selected based on their collective contribution to the optimal separation
      between patients with acute cerebral infarction and control subjects with a
      sensitivity of 84.4% and specificity of 95.0%, respectively. Plasma proteomic
      profiling with SELDI-TOF-MS and ProteinChip technologies shows potential in
      discriminating patients with acute cerebral infarction and control subjects.
      Diagnosis of acute cerebral infarction should probably depend on the use of a
      panel of biomarkers.

PMID- 18628102
TI  - Inflammatory markers, amino-terminal pro-brain natriuretic peptide, and mortality
      risk in dyspneic patients.
AB  - Dyspnea is a common emergency department (ED) complaint, and it may be associated
      with significant mortality risk. We studied 599 dyspneic subjects enrolled in an
      ED. At 1 year, the role of inflammatory markers (including C-reactive protein
      [CRP]) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) as
      independent predictors of mortality was assessed. By 1 year, 91 subjects (15.2%)
      had died. Among patients who died, the median CRP concentration at admission was
      significantly higher than in survivors: 47.2 mg/L (449.5 nmol/L; interquartile
      range [IQR], 10.2-101.9 mg/L [97.1-970.5 nmol/L]) vs 7.25 mg/L (69.5 nmol/L; IQR,
      2.2-29.6 mg/L [21.0-281.9 nmol/L]; P < .001). For 1-year mortality, CRP had an
      area under the receiver operating characteristic curve of 0.76 (95% confidence
      interval [CI], 0.69-0.80; P < .001). In multivariable analysis, a CRP
      concentration greater than 14 mg/L was a strong predictor of mortality at 1 year
      (hazard ratio, 2.47; 95% CI, 1.51-4.02; P < .001). In multivariable models, CRP
      and NT-proBNP demonstrated independent and additive prognostic value. Among
      dyspneic patients, CRP levels are significantly associated with mortality at 1
      year and show additive value to natriuretic peptide testing for prognosis.

PMID- 18628103
TI  - Head-putter coordination patterns in expert and less skilled golfers.
AB  - The authors examined the patterns of expert and less skilled golfers in putting
      on an indoor surface to 1 of 3 circular targets (1, 3, and 5 m away) in trials
      with a ball present (and putted) or not present (a practice stroke). As expected,
      the experts performed better than the less skilled golfers on a large number of
      outcome and kinematic measures. Displacement and velocity profiles of the head
      and putter revealed high positive correlations for the less skilled golfers,
      indicating a dominant allocentric coordination pattern, but high negative
      correlations for the expert golfers, indicating a dominant egocentric
      coordination pattern. The observed coordination patterns did not interact with
      the distance of the intended putt or the presence/absence of a ball. These
      findings offer preliminary evidence that, although contrary to traditional
      beliefs, fundamental differences exist in putting coordination modes between
      expert and less skilled golfers.

PMID- 18628104
TI  - Performance-based adaptive schedules enhance motor learning.
AB  - Although investigators have shown that random scheduling of several tasks
      enhances learning more than blocked scheduling does, the advantages of random
      scheduling may be limited because it does not take into account the nominal
      difficulty of each task, the difference in difficulty between tasks, and the
      skill level of the learner in that type of schedule. The authors propose 2 new
      algorithms for adaptively determining the nominal difficulty and the number of
      trials for each task on the basis of both current and delayed performance of the
      learner (N = 48). The authors tested the adaptive algorithms in a 2 x 2 factorial
      design, and they show that the algorithms outperform random scheduling when
      performance is measured on a delayed retention test.

PMID- 18628105
TI  - Effects of mental imagery styles on shoulder and hip rotations during preparation
      of pirouettes.
AB  - To analyze individual behavior in spatial navigation especially for pirouette
      preparations (complete whole-body rotations), the authors studied horizontal
      shoulder-hip interactions under 2 constraints: postural (right and left
      supporting legs [SL]) and spatial (clockwise [CW] and counterclockwise [CCW]).
      They performed kinematic analysis at the start and end of the shoulder-hip
      horizontal rotations (run-up) with regard to imagery of motor actions. On the
      basis of the Vividness of Movement Imagery Questionnaire, they classified 8
      female expert ballet dancers and 7 untrained female participants according to
      their movement imagery style (kinesthetic and visual). At the run-up's end, the
      shoulders initiated the turn independently of SL but differently depending on
      training: CW for dancers and CCW for untrained participants (their commonly used
      direction). Kinesthetic and mixed imagery styles prevailed in dancers, whereas
      simply a mixed style appeared among untrained participants. Thus, dance training
      enhances the imagery of kinesthetic sensation and influences the choice of
      spatial direction, facilitating the body-space interaction.

PMID- 18628106
TI  - Overproduction timing errors in expert dancers.
AB  - The authors investigated how expert dancers achieve accurate timing under various
      conditions. They designed the conditions to interfere with the dancers' attention
      to time and to test the explanation of the interference effect provided in the
      attentional model of time processing. Participants were 17 expert contemporary
      dancers who performed a freely chosen duration while walking and executing a
      bilateral cyclic arm movement over a given distance. The dancers reproduced that
      duration in different situations of interference. The process yielded temporal
      overproductions, validating the attentional model and extending its application
      to expert populations engaged in complex motor situations. The finding that the
      greatest overproduction occurred in the transfer-with-improvisation condition
      suggests that improvisation within a time deadline requires specific training.

PMID- 18628108
TI  - Coupling of the reach and grasp phase during catching in children with
      developmental coordination disorder.
AB  - The authors studied 2-handed catching behavior in 10 children with developmental
      coordination disorder (DCD), aged 7-10 years old, and their typically developing
      peers (TDC). Participants performed 15 catches, and the authors examined
      kinematics of both transport and grasp phases. In terms of the transport phase,
      movement initiation and movement time was longer and peak deceleration was
      earlier in children with DCD. In addition, such children initiated the grasp
      phase earlier, and their maximal grasp aperture was larger. In children with DCD,
      the time to maximal grasp aperture was more variable, and that aperture was
      earlier when the authors examined it with respect to the transport phase of the
      catch. The data suggest that children with DCD may use a decomposition strategy
      to simplify the movement control of the transport and grasp phases of a catch.

PMID- 18628107
TI  - Changes in the relationship between movement velocity and movement distance in
      primary focal hand dystonia.
AB  - The authors examined the relationship between movement velocity and distance and
      the associated muscle activation patterns in 18 individuals with focal hand
      dystonia (FHD) compared with a control group of 18 individuals with no known
      neuromuscular condition. Participants performed targeted voluntary wrist and
      elbow flexion movements as fast as possible across 5 movement distances.
      Individuals with FHD were slower than controls across all distances, and this
      difference was accentuated for longer movements. Muscle activation patterns were
      triphasic in the majority of individuals with FHD, and muscle activation scaled
      with distance in a similar manner to controls. Cocontraction did not explain
      movement slowing in individuals with dystonia, but there was a trend toward
      underactivation of the 1st agonist burst in the dystonic group. The authors
      concluded that slowness is a consistent feature of voluntary movement in FHD and
      is present even in the absence of dystonic posturing. Underactivation of the 1st
      agonist burst appears to be the most likely reason to explain slowing.

PMID- 18628110
TI  - Visual guidance for hand advance but not hand withdrawal in a reach-to-eat task
      in adult humans: reaching is a composite movement.
AB  - Many animal species use reaching for food to place in the mouth (reach-to-eat)
      with a hand, and it may be a primitive movement. Although researchers (I. Q.
      Whishaw, 2005; A. N. Iwaniuk & I. Q. Whishaw, 2000; M. Gentiluci, I. Toni, S.
      Chieffi, & G. Pavesi, 1994) have described visual guidance of reaching in both
      normal and brain-injured human and nonhuman primates, researchers have not
      described the contribution of vision during advance of the limb to grasp food and
      during withdrawal of the limb with food to the mouth. To evaluate visual
      contributions, the authors monitored eye movements in young adults as they
      reached for food with and without vision. Participants visually engaged the
      target prior to the 1st hand movement and disengaged it as the food was grasped.
      Visual occlusion slowed limb advance and altered digit shaping but did not affect
      withdrawal. The dependence on visual control of advance but not withdrawal
      suggests that the reach-to-eat movement is a composite of 2 basic movements under
      visual and tactile/proprioceptive guidance, respectively.

PMID- 18628109
TI  - Sequential processes for controlling distance in multijoint movements.
AB  - The purpose of this study was to examine the mechanisms underlying control of
      distance during multijoint movements in different directions. The findings
      revealed 2 sequential muscle torque impulses, which correlated with 2 events in
      the hand acceleration profile. These 2 events occurred prior to peak velocity,
      characterizing control in the initial acceleration phase of motion. The
      contribution of shoulder and elbow joint torque to each event varied with
      movement direction. However, regardless of direction, these 2 torque events
      appeared to be functionally distinguishable: a preplanned initiation event was
      responsible for the initial hand acceleration, whereas a 2nd modulation event
      adjusted acceleration in compensation for variations in acceleration. Thus, the
      findings support the idea that control of distance during multijoint movement
      occurs through sequential control mechanisms.

PMID- 18628111
TI  - Precocity of fine motor control and task context: hitting a ball while stepping.
AB  - To determine if children under 5 years were able to intercept a moving object
      while stepping, the authors had 9 3-year-olds hit a ball that the authors dropped
      from a ramp from 5 heights (1.5, 2.0, 2.5, 3.0, and 3.5 m). The statistical
      analysis showed that the hand movement times were similar regardless of ball
      rolling heights and that the hand initiation times were dependent on the ball
      rolling times. Children under 5 years were able to hit a moving ball, and they
      performed this hitting according to a temporal coupling between ball
      displacements and the hand contact with it. The participants' behavior of hitting
      while stepping supports the idea that the motor system implicitly knows what the
      cognitive system ignores.

PMID- 18628112
TI  - Experimental heating reveals nest temperature affects nestling condition in tree
      swallows (Tachycineta bicolor).
AB  - Investment in one life-history stage can have delayed effects on subsequent life
      history stages within a single reproductive bout. We experimentally heated tree
      swallow (Tachycineta bicolor) nests during incubation to test for effects on
      parental and nestling conditions. Females incubating in heated boxes maintained
      higher body condition and fed nestlings at higher rates. We cross-fostered
      nestlings and found that young nestlings (4-7 days old) incubated in heated nests
      had higher body condition and body mass, regardless of treatment status of their
      rearing parent. However, older nestlings which were fed by heated females
      maintained higher condition and body mass regardless of treatment status of their
      incubating parent. These results indicate that investment in one life-history
      stage can have multiple pathways of carry-over effects on future life-history
      stages.

PMID- 18628113
TI  - Apparent density patterns in subchondral bone of the sloth and anteater forelimb.
AB  - Vertebrate morphologists often are interested in inferring limb-loading patterns
      in animals characterized by different locomotor repertoires. Because bone
      apparent density (i.e. mass per unit volume of bone inclusive of porosities) is a
      determinant of compressive strength, and thus indicative of compressive loading,
      recent comparative studies in primates have proposed a structure-function
      relationship between apparent density of subchondral bone and locomotor
      behaviours that vary in compressive loading. If such patterns are found in other
      mammals, then these relationships would be strengthened further. Here, we examine
      the distal radius of suspensory sloths that generally load their forelimbs (FLs)
      in tension and of quadrupedal anteaters that generally load their FLs in
      compression. Computed tomography osteoabsorptiometry was used to visualize the
      patterns in subchondral apparent density. Suspensory sloths exhibit relatively
      smaller areas of high apparent density than quadrupedal anteaters. This locomotor
      based pattern is analogous to the pattern observed in suspensory and quadrupedal
      primates. Similarity between xenarthran and primate trends suggests broad-scale
      applicability for analysing subchondral bone apparent density and supports the
      idea that bone functionally alters its material properties in response to
      locomotor behaviours.

PMID- 18628114
TI  - Climate-mediated mechanical changes to post-disturbance coral assemblages.
AB  - Increasingly severe storms and weaker carbonate materials associated with more
      acidic oceans will increase the vulnerability of reef corals to mechanical
      damage. Mechanistic predictions based on measurements of colony mechanical
      vulnerability and future climate scenarios demonstrate dramatic shifts in
      assemblage structure following hydrodynamic disturbances, including switches in
      species' dominance on the reef and thus potential for post-disturbance recovery.
      Larger colonies are more resistant to factors such as disease and competition for
      space, and complex morphologies support more associated reef species. Future
      reefs are thus expected to have lower colony abundances and be dominated by small
      and morphologically simple, yet mechanically robust species, which will in turn
      support lower levels of whole-reef biodiversity than do present-day reefs.

PMID- 18628115
TI  - Size-selective dispersal of Daphnia resting eggs by backswimmers (Notonecta
      maculata).
AB  - Freshwater zooplankton is increasingly used to study effects of dispersal on
      community and metacommunity structure. Yet, it remains unclear how zooplankton
      disperses. Clearly, birds and wind play a significant role as zooplankton
      dispersal agents, but they may not always be the main vectors. This experimental
      study shows that a cosmopolitan aquatic insect, Notonecta, can be an important
      vector of cladoceran resting eggs (ephippia). Dispersing Notonecta frequently
      transported ephippia during flight, with a bias towards smaller ephippia in two
      species. A similar trend was present at the species level: Daphnia species with
      smaller ephippia were more often dispersed, suggesting that Notonecta could
      generate specific colonist communities. In addition, buoyancy appeared a critical
      trait, as non-floating ephippia of Daphnia magna were never dispersed. Our data
      suggest that Notonecta could be important dispersers of Daphnia, and that
      knowledge of dispersal dynamics of Notonecta may be used to predict Daphnia
      dispersal, colonization and resilience to disturbance.

PMID- 18628116
TI  - Immune response impairs learning in free-flying bumble-bees.
AB  - Parasites can influence different host behaviours including foraging, mate choice
      and predator avoidance. Several recent papers have shown reduced learning
      abilities in infected insects. However, it is difficult to separate the effects
      of the immune response from the direct effects of the parasite. Using a free
      flying learning paradigm, this paper shows that learning performance is impaired
      in bumble-bees (Bombus terrestris) that are not infected but whose immune system
      is stimulated non-pathogenically. This demonstrates that before it is assumed
      that a parasite has a direct effect on a host's behaviour, the effect of the
      immune response stimulated by the parasite must first be quantified.

PMID- 18628117
TI  - Expression of arginine vasotocin in distinct preoptic regions is associated with
      dominant and subordinate behaviour in an African cichlid fish.
AB  - Neuropeptides have widespread modulatory effects on behaviour and physiology and
      are associated with phenotypic transitions in a variety of animals. Arginine
      vasotocin (AVT) is implicated in mediating alternative male phenotypes in teleost
      fish, but the direction of the association differs among species, with either
      higher or lower AVT related to more territorial behaviour in different fishes. To
      clarify the complex relationship between AVT and alternative phenotype, we
      evaluated AVT expression in an African cichlid in which social status is
      associated with divergent behaviour and physiology. We compared AVT mRNA
      expression between territorial and non-territorial (NT) males in both whole
      brains and microdissected anterior preoptic areas using transcription profiling,
      and in individual preoptic nuclei using in situ hybridization. These
      complementary methods revealed that in the posterior preoptic area
      (gigantocellular nucleus), territorial males exhibit higher levels of AVT
      expression than NT males. Conversely, in the anterior preoptic area
      (parvocellular nucleus), AVT expression is lower in territorial males than NT
      males. We further correlated AVT expression with behavioural and physiological
      characteristics of social status to gain insight into the divergent functions of
      individual AVT nuclei. Overall, our findings highlight a complex association
      between AVT and social behaviour.

PMID- 18628118
TI  - Environmental variation at the onset of independent foraging affects full-grown
      body mass in the red fox.
AB  - The period following the withdrawal of parental care has been highlighted as a
      key developmental period for juveniles. One reason for this is that juveniles
      cannot forage as competently as adults, potentially placing them at greater risk
      from environmentally-induced changes in food availability. However, no study has
      examined this topic. Using a long-term dataset on red foxes (Vulpes vulpes), we
      examined (i) dietary changes that occurred in the one-month period following the
      attainment of nutritional independence, (ii) diet composition in relation to
      climatic variation, and (iii) the effect of climatic variation on subsequent full
      grown mass. Diet at nutritional independence contained increased quantities of
      easy-to-catch food items (earthworms and insects) when compared with pre
      independence. Interannual variation in the volume of rainfall at nutritional
      independence was positively correlated to the proportion of earthworms in cub
      diet. Pre-independence cub mass and rainfall immediately following nutritional
      independence explained a significant proportion of variance in full-grown mass,
      with environmental variation affecting full-grown mass of the entire cohorts.
      Thus, weather-mediated availability of easy-to-catch food items at a key
      developmental stage has lifelong implications for the development of juvenile
      foxes by affecting full-grown mass, which in turn appears to be an important
      component of individual reproductive potential.

PMID- 18628119
TI  - Summation of perceptual cues in natural visual scenes.
AB  - Natural visual scenes are rich in information, and any neural system analysing
      them must piece together the many messages from large arrays of diverse feature
      detectors. It is known how threshold detection of compound visual stimuli
      (sinusoidal gratings) is determined by their components' thresholds. We
      investigate whether similar combination rules apply to the perception of the
      complex and suprathreshold visual elements in naturalistic visual images.
      Observers gave magnitude estimations (ratings) of the perceived differences
      between pairs of images made from photographs of natural scenes. Images in some
      pairs differed along one stimulus dimension such as object colour, location, size
      or blur. But, for other image pairs, there were composite differences along two
      dimensions (e.g. both colour and object-location might change). We examined
      whether the ratings for such composite pairs could be predicted from the two
      ratings for the respective pairs in which only one stimulus dimension had
      changed. We found a pooling relationship similar to that proposed for simple
      stimuli: Minkowski summation with exponent 2.84 yielded the best predictive power
      (r=0.96), an exponent similar to that generally reported for compound grating
      detection. This suggests that theories based on detecting simple stimuli can
      encompass visual processing of complex, suprathreshold stimuli.

PMID- 18628121
TI  - Dynamics of haemopoiesis across mammals.
AB  - Haemopoiesis is a fundamental physiologic process found in many animals. Among
      mammals, the diversity in size and function required suitable adaptations of this
      process. In this work, we use allometric principles to determine whether this
      required a change in the basic architecture of haemopoiesis. We show that it is
      possible to express both the number and rate with which haemopoietic stem cells
      replicate as well as total marrow output across all mammals as a function of
      adult mass. This unified view, which is compatible with the existing data,
      suggests that there was no need for major adaptations in the architecture of
      haemopoiesis across mammals.

PMID- 18628120
TI  - Convergence and divergence are mostly reciprocated properties of the connections
      in the network of cortical areas.
AB  - Cognition is based on the integrated functioning of hierarchically organized
      cortical processing streams in a manner yet to be clarified. Because integration
      fundamentally depends on convergence and the complementary notion of divergence
      of the neuronal connections, we analysed integration by measuring the degree of
      convergence/divergence through the connections in the network of cortical areas.
      By introducing a new index, we explored the complementary convergent and
      divergent nature of connectional reciprocity and delineated the backward and
      forward cortical sub-networks for the first time. Integrative properties of the
      areas defined by the degree of convergence/divergence through their afferents and
      efferents exhibited distinctive characteristics at different levels of the
      cortical hierarchy. Areas previously identified as hubs exhibit information
      bottleneck properties. Cortical networks largely deviate from random graphs where
      convergence and divergence are balanced at low reciprocity level. In the cortex,
      which is dominated by reciprocal connections, balance appears only by further
      increasing the number of reciprocal connections. The results point to the
      decisive role of the optimal number and placement of reciprocal connections in
      large-scale cortical integration. Our findings also facilitate understanding of
      the functional interactions between the cortical areas and the information flow
      or its equivalents in highly recurrent natural and artificial networks.

PMID- 18628122
TI  - Avian olfactory receptor gene repertoires: evidence for a well-developed sense of
      smell in birds?
AB  - Among vertebrates, the sense of smell is mediated by olfactory receptors (ORs)
      expressed in sensory neurons within the olfactory epithelium. Comparative genomic
      studies suggest that the olfactory acuity of mammalian species correlates
      positively with both the total number and the proportion of functional OR genes
      encoded in their genomes. In contrast to mammals, avian olfaction is poorly
      understood, with birds widely regarded as relying primarily on visual and
      auditory inputs. Here, we show that in nine bird species from seven orders (blue
      tit, Cyanistes caeruleus; black coucal, Centropus grillii; brown kiwi, Apteryx
      australis; canary, Serinus canaria; galah, Eolophus roseicapillus; red jungle
      fowl, Gallus gallus; kakapo, Strigops habroptilus; mallard, Anas platyrhynchos;
      snow petrel, Pagodroma nivea), the majority of amplified OR sequences are
      predicted to be from potentially functional genes. This finding is somewhat
      surprising as one previous report suggested that the majority of OR genes in an
      avian (red jungle fowl) genomic sequence are non-functional pseudogenes. We also
      show that it is not the estimated proportion of potentially functional OR genes,
      but rather the estimated total number of OR genes that correlates positively with
      relative olfactory bulb size, an anatomical correlate of olfactory capability. We
      further demonstrate that all the nine bird genomes examined encode OR genes
      belonging to a large gene clade, termed gamma-c, the expansion of which appears
      to be a shared characteristic of class Aves. In summary, our findings suggest
      that olfaction in birds may be a more important sense than generally believed.

PMID- 18628123
TI  - Demographic mechanism of a historical bird population collapse reconstructed
      using museum specimens.
AB  - Long-term studies of demographic rates provide clues about the external causes of
      animal population declines, but systematic monitoring is rarely in place until
      after the decline has occurred. This study evaluates alternative hypotheses about
      the demographic mechanisms underlying the historical collapse of corncrake
      (Crexcrex) populations in Britain and Ireland in the late nineteenth and early
      twentieth centuries using characteristics of museum specimens. The proportion of
      adult corncrakes that are 1-year old was estimated from feather characteristics
      of birds collected before, during and after the population decline and showed a
      marked transitory reduction during the decline. This pattern would be expected if
      the decline was caused by a large reduction in the recruitment of young birds to
      the breeding population and is the opposite of what would be expected if a change
      in adult survival had caused the decline. These results are consistent with
      previous suggestions that the corncrake population decline was caused by adverse
      effects on breeding productivity caused by the mechanization of the harvesting of
      hay crops.

PMID- 18628124
TI  - Expanding the horizons of supportive therapy.

PMID- 18628125
TI  - Highlights from: The 39th Annual Meeting of the American Society of Clinical
      Oncology; Chicago, Illinois.

PMID- 18628126
TI  - Early initiation of epoetin alfa prevents development of chemotherapy-associated
      anemia and preserves quality of life.

PMID- 18628127
TI  - The use of recombinant human keratinocyte growth factor (palifermin) to
      ameliorate treatment-induced mucositis.

PMID- 18628128
TI  - Epidemiology of febrile neutropenia.
AB  - Febrile neutropenia (FN) continues to represent a major cause of morbidity,
      mortality, and cost in patients receiving cancer chemotherapy. The reported rates
      of FN vary considerably among studies depending on the treatment regimen,
      delivered dose intensity, and patient population. The risk of initial FN appears
      to be highest during the first cycle of chemotherapy and is greatest in certain
      high-risk groups including elderly patients and those with various comorbidities.
      Febrile neutropenia continues to have considerable clinical, economic, and
      quality-of-life impact on affected patients. The risk of mortality associated
      with FN continues to be relatively high in patients with hematologic
      malignancies, patients presenting with comorbid illnesses, and patients with
      bacteremia, pneumonia, or other infection-related complications. The reduction in
      chemotherapy dose intensity that frequently follows an episode of FN may have
      considerable life-threatening impact on disease control in responsive and
      potentially curable malignancies. The economic burden of FN is substantial, with
      the greatest proportion of the cost associated with the relatively limited number
      of patients hospitalized for prolonged periods as a result of comorbidities or
      complications. The colony-stimulating factors (CSFs) may reduce the risk and cost
      associated with cancer treatment by reducing the probability of hospitalization
      with FN. Primary prophylaxis with the CSFs may be warranted in patients receiving
      intensive regimens or in those at greater risk because of age or comorbidities.
      Further study of various risk factors for FN should help identify patients at
      greatest risk and likely candidates for targeted use of the hematopoietic growth
      factors.

PMID- 18628129
TI  - Hematopoietic cytokines: when treating the symptoms does not treat the disease.

PMID- 18628130
TI  - Unique aspects of supportive care using monoclonal antibodies in cancer
      treatment.
AB  - The "magic bullet" era of targeted cancer therapy began with the United States
      Food and Drug Administration approval of rituximab for the treatment of B-cell
      lymphoma in the late fall of 1997. Since then, several additional anticancer
      antibody products have received regulatory approval, including the monoclonal
      antibodies (MoAbs) trastuzumab for breast cancer and alemtuzumab for chronic
      lymphocytic leukemia, and the MoAb immunoconjugates gemtuzumab ozogamicin for
      acute myelogenous leukemia and yttrium 90 ibritumomab tiuxetan for B-cell
      lymphoma. These products are associated with adverse events that are quite
      different than those seen with chemotherapy. Adverse events associated with MoAb
      products typically have 1 of 3 etiologies: direct and indirect effects of
      antibody-antigen interaction, effects of toxins or radioisotopes that have been
      conjugated to antibodies, and allergic and hypersensitivity reactions to foreign
      protein. The infusion-related symptom complex is the most common and predictable
      side effect associated with all MoAbs that react with circulating blood cells.
      This pattern of various systemic effects includes flu-like symptoms such as
      headache, shortness of breath, fever, skin rash, hypotension, nausea, and
      asthenia, but usually occurs only in association with the first of any series of
      weekly infusions. The severity of these reactions is influenced by the rate of
      infusion, and the syndrome is the consequence of cytokines released from immune
      cells. Severe hypotension, bronchospasm, hypoxia, and even death have occurred. A
      true tumor lysis syndrome may occur if there are large numbers of proliferating
      antigen-positive cells in the blood. Symptoms related to the infusion reaction
      are ameliorated by slowing or stopping the infusion and administering
      antiinflammatory agents and antihistamines.

PMID- 18628131
TI  - Hemoglobin increase is associated with improved health-related quality of life in
      patients with cancer not receiving chemotherapy.
AB  - Anemia is becoming recognized as a substantial problem for patients with cancer
      who are not receiving chemotherapy. Recently, darbepoetin alfa has been shown to
      provide significant clinical benefits in this patient population. This analysis
      assesses the effect of change in hemoglobin levels on health-related quality of
      life (HRQOL) in these patients. Eligible patients had anemia (hemoglobin </= 11
      g/dL), had nonmyeloid malignancy, and had not received cytotoxic chemotherapy or
      radiation therapy </= 8 weeks before the study. Fatigue and other HRQOL outcomes
      were measured using the Functional Assessment of Cancer Therapy (FACT) General
      and Fatigue subscales, the Brief Symptom Inventory depression and anxiety
      subscales, and numeric rating scales of energy, activity, and overall health.
      Improvements in hemoglobin were significantly associated with reductions in
      fatigue (P < 0.001), improvements in functional (P < 0.0001) and physical (P =
      0.001) well-being, depression (P = 0.023), anxiety (P = 0.022), and global
      ratings of energy (P = 0.0004), activity (P = 0.0008), and overall health (P =
      0.003). Clinically meaningful improvements in fatigue (defined as an increase in
      FACT-Fatigue subscale score of >/= 3 points) were significantly (P < 0.05)
      associated with improvements in functional, physical, and emotional well-being,
      depression, anxiety, and global ratings of energy, activity, and overall health.
      In summary, an increase in hemoglobin was associated with a decrease in fatigue
      in patients with anemia associated with nonmyeloid malignancies who were not
      receiving chemotherapy.

PMID- 18628132
TI  - Preoperative assessment of cancer in elderly patients: a pilot study.
AB  - The aim of this study was to assess the face validity and practical utility of
      the Preoperative Assessment of Cancer in the Elderly (PACE) tool in a sample of
      elderly patients with cancer. A prospective series of such patients with breast,
      colorectal, upper gastrointestinal, and other cancers were interviewed using the
      PACE; patients were scored for presurgical assessment using standard measures,
      including American Society of Anesthesiologists physical status, the
      Physiological and Operative Severity Score for Enumeration of Mortality and
      Morbidity (POSSUM), the Portsmouth POSSUM, and World Health Organization
      performance status before undergoing standard surgical management. Short-term
      surgical outcome (in terms of mortality and morbidity) and cancer site-specific
      data were collected to identify the risk groups. Seventy-two patients took part
      in the study (participation rate of 97%). The interview in which the
      questionnaire was given was found to take 20 minutes on average. Face validity
      was demonstrated, with clear comprehension of the requirements of the PACE being
      shown by all patients. The 2 groups identified according to the presence (n = 24)
      or absence (n = 48) of postoperative mortality/morbidity were compared according
      to components of the PACE. The study identified possible associations between
      these components and postoperative morbidity. No postoperative mortality was
      recorded; however, 24 patients (33%) had surgical complications. Performance
      status and Activities of Daily Living classification were found to be
      significantly related to postoperative short-term morbidity, whereas a lower
      score on the Mini Mental State Examination and a higher score on the Geriatric
      Depression Scale were found to be related to postoperative morbidity, although
      they did not achieve statistical significance because of the small numbers
      involved. The authors have demonstrated the practicality and face validity of
      PACE and identified some associations with postoperative morbidity. Based on the
      findings of this pilot study, a large, international multicenter trial is
      planned.

PMID- 18628133
TI  - Highlights from: The 2nd Annual Future of Supportive Therapy in Oncology; St.
      Kitts, West Indies.

PMID- 18628134
TI  - Control of chemotherapy-induced emesis with 5-hydroxytryptamine-3 antagonists.

PMID- 18628135
TI  - Impact of correction of anemia on clinical outcome in patients with cancer:
      recent data from head and neck and breast cancer trials.

PMID- 18628136
TI  - The management of bone loss in patients with breast or prostate cancer.
AB  - Osteoporosis is a disease that is associated with significant morbidity and
      mortality, much of which can be prevented with available therapy. The risk for
      osteoporosis is increased in individuals with some types of cancer, especially in
      women with breast cancer and men with prostate cancer. This is caused by several
      factors, including premature ovarian failure and systemic antihormonal therapy in
      women, androgen ablation therapy in men, and potential direct effects of
      chemotherapy and of cancer on bone metabolism. With continual increases in the
      incidence of breast cancer, earlier detection and treatment, and improvements in
      survival for both patients with breast and prostate cancer, the importance of
      appropriate screening for and management of osteoporosis is evident. We review
      the evidence supporting an increased risk for development of osteoporosis in
      individuals with breast or prostate cancer, and strategies for prevention and
      treatment of osteoporosis in these patients.

PMID- 18628137
TI  - Strategies for pain management: cleveland clinic foundation guidelines for opioid
      dosing for cancer pain.
AB  - Pain remains the most common distressing symptom in advanced cancer. Opioids are
      the most effective drugs for pain currently available. Analgesia depends largely
      on appropriate administration. Cancer clinicians should be proficient in opioid
      pharmacotherapy. Although knowledge of general opioid dosing principles is
      helpful, in practice, complex clinical scenarios often arise, requiring more
      sophisticated and precise dosing maneuvers for which there is very little
      evidence-based literature. Familiarity with specific strategies indicated for
      common clinical problems provides a more focused approach and increases the
      likelihood of therapeutic success. This article enumerates cancer pain scenarios
      compiled from our palliative medicine practice and the opioid dosing strategies
      used by the palliative medicine department within the Cleveland Clinic
      Foundation.

PMID- 18628138
TI  - Leukocytosis and Mobilization of CD34+ Hematopoietic Progenitor Cells by AMD3100,
      a CXCR4 Antagonist.
AB  - Stromal cell-derived factor-1 (SDF-1/CXCL12) plays a key regulatory role in the
      trafficking of hematopoietic cells. AMD3100 is a specific antagonist of the
      binding of SDF-1 to its receptor, CXCR4. This phase I study assessed the
      hematological effects, pharmacokinetics, and safety of administration of AMD3100
      to 32 healthy volunteers, including its ability to mobilize CD34+ hematopoietic
      progenitor cells. A generalized leukocytosis occurred after a single subcutaneous
      injection of AMD3100 (80 microg/kg) resulting in a maximum white blood cell count
      of 19.49 +/- 1.27 x 103/microL (mean +/- SEM) at 6 hours. No changes were
      observed in erythrocyte or platelet counts. Circulating CD34+ cells increased 5
      fold after administration of AMD3100 at 80 mug/kg and 15.5-fold in response to
      AMD3100 at 240 mug/kg, both at 9 hours after injection. Myeloid progenitor cells
      colony forming unit granulocytemacrophage (CFU-GM); CFU-granulocyte, eosinophil,
      monocyte, megakaryocyte (CFU-GEMM); and burst forming units-erythroid showed
      similar increases in mobilization to the blood with increasing doses of AMD3100.
      The mobilized cells were in a slow or noncycling state as determined by in vitro
      high specific activity of 3H-thymidine. Pharmacokinetic studies showed a near
      linear increase in peak drug levels with increasing doses and nearly complete
      elimination of the drug by 24 hours. AMD3100 was well tolerated with only mild
      and transient toxicities (injection site erythema, headache, paresthesia, nausea,
      and abdominal distension) observed. These observations suggest that AMD3100 may
      be a clinically useful agent for hematopoietic progenitor cell mobilization.

PMID- 18628139
TI  - Quality of life after local external beam radiation therapy for symptomatic bone
      metastases: a prospective evaluation.
AB  - This study was designed to prospectively evaluate quality of life in patients
      treated with local external beam radiation therapy for symptomatic bone
      metastases. Patients with symptomatic bone metastases treated with palliative
      radiation therapy were followed with Edmonton Symptom Assessment Scale (ESAS) at
      baseline and at 1, 2, 4, 8, and 12 weeks after the delivery of radiation therapy.
      The ESAS evaluates 10 symptoms: global pain, index pain (pain at the irradiated
      site), fatigue, nausea, depression, anxiety, drowsiness, appetite, sense of well
      being, and shortness of breath on a categorical score of 0 to 10 (0 = absence of
      symptom, 10 = worst possible symptom). At each follow-up interval, the difference
      for each domain of the ESAS was compared with the baseline score. A P value <
      0.01 was considered significant. Five hundred and eighteen patients were analyzed
      in this study. For the entire cohort, there were statistically significant
      improvements with the delivery of palliative radiation therapy in global pain,
      index pain, anxiety, sense of wellbeing, and shortness of breath in >/= 1 follow
      up interval. Fatigue was reported to be slightly worse in the first 2 weeks
      following the radiation treatment. Global pain, index pain, anxiety, and sense of
      well-being showed consistent improvement with the radiation treatment regardless
      of which endpoint definitions were employed. Radiation therapy not only can
      palliate pain but also can improve quality of life.

PMID- 18628140
TI  - What is the evidence for implantable drug delivery systems for refractory cancer
      pain?
AB  - Despite best management, 14% of patients with cancer have unrelieved pain and
      many more have undesirable side effects from pain medicines. Intrathecal
      implantable drug delivery systems (IDDSs) manage intractable cancer pain by
      delivering pain medications directly to the spinal fluid. In addition to data
      from many nonrandomized trials, there are now randomized clinical trial data
      showing better clinical success, pain relief, drug toxicity control, and perhaps
      survival compared with comprehensive medical management (CMM). We reviewed
      published cohort reports from 1980 through 2003 using Medline. We studied 202
      patients with unrelieved pain on visual analogue scale (VAS) pain scores of >/= 5
      on a scale of 0-10 despite conventional management. The main outcome measure was
      clinical success, defined as a 20% improvement in pain control and composite drug
      toxicity. We ranked the trials according to accepted levels of evidence. The
      nonrandomized trials all showed pain relief with acceptable complication rates,
      but often did not have standardized assessment schemas, had no control groups,
      and were single-institutional trials. In the randomized trial, more patients had
      clinical success with IDDS (84.5%) than with CMM (70.5%, P < 0.05). After 4
      weeks, the mean VAS pain score decreased from the baseline of 7.75 to 4.74 (39%
      reduction) in the CMM group and from 7.45 to 3.59 (52% reduction) in the IDDS
      group (P = 0.057). The drug toxicity scores decreased from the baseline of 6.35
      to 5.18 (19% reduction) in the CMM group and from 7.14 to 3.46 (52% reduction) in
      the IDDS group (P = 0.01). All individual toxicities were improved more by IDDS,
      especially fatigue and depressed level of consciousness. Patients randomized to
      IDDS therapy had improved survival, with 53.9% alive at 6 months compared with
      37.2% of the CMM group (P = 0.06). There is now high-level randomized clinical
      trial evidence, in addition to consistent nonrandomized evidence, that IDDSs
      reduce pain and common drug toxicities and are associated with improved survival.
      Added to the multiple cohort studies, the evidence is compelling in favor of
      IDDS.

PMID- 18628141
TI  - One year of supportive cancer therapy.

PMID- 18628142
TI  - Highlights from: The 40th Annual Meeting of the American Society of Clinical
      Oncology; New Orleans, LA.

PMID- 18628144
TI  - Current strategies to minimize treatment-associated hot flashes in patients with
      breast cancer.

PMID- 18628143
TI  - Prophylactic pegfilgrastim significantly reduces febrile neutropenia during
      moderately myelosuppressive chemotherapy.

PMID- 18628145
TI  - Chemotherapy-induced palmar-plantar erythrodysesthesia syndrome: etiology and
      emerging therapies.
AB  - Palmar-plantar erythrodysesthesia, or hand-foot syndrome (HFS), is emerging as a
      common, dose-dependent toxicity of many newer chemotherapy drugs. Frequently, HFS
      is a dose-limiting toxicity requiring discontinuation of treatment, chemotherapy
      dose reductions, or delays. The spectrum of symptoms of HFS can be mild, with
      erythema of the distal extremities, or it can be severe enough to interfere with
      activities of daily living. Although the exact mechanism is unknown, there are
      several approaches to ameliorating the symptoms of this complication. These
      include antiinflammatory agents, vitamin products, and peripheral
      vasoconstricting agents.

PMID- 18628146
TI  - Oral complications and management considerations in patients treated with high
      dose chemotherapy.
AB  - Oral sequelae of high-dose chemotherapy, including conditioning chemotherapy for
      hematopoietic stem cell transplantation, can lead to significant morbidity
      including potentially serious systemic infectious complications. These
      complications reduce the quality of life, are associated with higher treatment
      and supportive care costs, and can affect overall outcome of cancer therapy.
      Pretreatment oral assessment and intervention followed by the provision of
      supportive oral care during and after cancer therapy can reduce at least some of
      the adverse impact of oral complications. A definitive supportive oral care
      program is strongly recommended for patients scheduled for high-dose
      chemotherapeutic regimens. This article reviews recent insights into the
      pathogenesis of common oral problems in patients treated with high-dose
      chemotherapy regimens and discusses a multidisciplinary approach to management of
      these complications.

PMID- 18628147
TI  - Health-related quality of life in treatment for prostate cancer: looking beyond
      survival.
AB  - Improvements in detecting and treating prostate cancer account for the need to
      evaluate strategies for optimizing quality of life (QOL) among survivors of
      prostate cancer. Several management options are available when prostate cancer is
      diagnosed at an early stage. However, the optimal treatment for localized
      prostate cancer is unknown, and reports in the literature are controversial
      regarding the best treatment modality. In this article, the authors will review
      the standard therapies used to treat localized prostate cancer and the effects of
      these therapies on a patient's QOL. Ultimately, the decision of which treatment
      modality to choose will be a decision based largely on individual patient
      preferences in concert with his physician and family members, in view of a
      thorough understanding of the available treatments and the full range of possible
      treatment-related side effects.

PMID- 18628148
TI  - Tumor Necrosis Factor-alpha as a Treatment Target for the Cancer Anorexia/Weight
      Loss Syndrome.
AB  - The cancer-associated anorexia/weight loss syndrome occurs in > 50% of patients
      with advanced cancer. Associated with negative quality of life and diminished
      survival, this syndrome carries a devastating impact on patients with cancer. To
      date, efforts to manage this syndrome effectively have fallen short. However,
      recent data with therapy that targets the inflammatory cytokine tumor necrosis
      factor-alpha (TNF-alpha) appear promising. This article discusses some of the
      preliminary data that suggest that further study of anti-TNF- alpha is warranted.
      It also describes the study design of an ongoing North Central Cancer Treatment
      Group trial that is aimed at treating this syndrome with the agent infliximab.

PMID- 18628150
TI  - Year two for supportive cancer therapy.

PMID- 18628149
TI  - "...And how are things sexually?" helping patients adjust to sexual changes
      before, during, and after cancer treatment.
AB  - All types of cancer treatments are likely to disrupt patients' sexual lives. The
      disruption may be a temporary result of the immediate stress of the situation or
      may be long lasting. Regardless of the specific disease site and level of
      treatment, sexual concerns of patients and their partners should be anticipated
      and addressed. When ignored, issues of adjustment to sexual changes can lead to
      chronic sexual dysfunction that may affect all areas of a patient's self-image
      and functioning. This is a concern in all patients, but particularly in those
      whose illness or treatment medically affects sexual function. Because of the
      pivotal role of the oncology team personnel, and because of their intimate
      knowledge of their patients' medical situation, they are the most likely
      candidates to offer effective solutions to their patients' difficulties in
      adjusting to sexual changes and therefore to significantly influence the sexual
      outcomes of cancer treatment. Dissemination of information about sexual concerns
      regarding disease and possible treatment side effects that may affect sexual
      interest and function is the first line of intervention in helping patients
      prevent the development of sexual disruption. Pragmatic advice regarding
      management of sexual changes throughout cancer treatment and beyond should
      include the timing of sexual activity, communication with partners about sexual
      concerns, and even the use of lubricants and vibrators to optimize the experience
      of pleasure for the patients and their partners.

PMID- 18628151
TI  - Kyphoplasty in the management of cancer-associated vertebral compression
      fractures.

PMID- 18628152
TI  - Prevention and management of osteonecrosis of the jaw associated with
      bisphosphonate therapy.

PMID- 18628153
TI  - Incidence of thromboembolism and role of low molecular weight heparin in
      prolonging survival in patients with advanced malignancies.

PMID- 18628154
TI  - Approaches to management of invasive fungal infections in patients with
      hematologic malignancies.
AB  - Invasive fungal infections have become increasingly common in patients with
      hematologic malignancies, especially in those at high risk with prolonged
      neutropenia and graft versus host disease after allogeneic stem cell
      transplantation, and are associated with significant morbidity, mortality, and
      cost. New diagnostic techniques and therapeutic agents have emerged recently to
      assist in the management of these infections. The galactomannan assay in
      association with routine clinical and radiologic screening may assist in the
      early diagnosis of invasive aspergillosis such that therapy may be initiated
      early. Also, several new antifungal agents have become available, allowing the
      practitioner more options in the prevention and treatment of fungal infections.
      New antifungal agents such as the lipid amphotericin B products, voriconazole,
      and the echinocandins appear to be safer to use than conventional amphotericin B.
      Voriconazole also has shown superiority to conventional amphotericin B in the
      treatment of invasive aspergillosis, and its well absorbed oral formulation makes
      it an excellent treatment to complete therapy as an outpatient. All these
      therapeutic options allow physicians to tailor antifungal therapy to the
      individual patient based on response and toxicity to prevent or treat invasive
      fungal infections. There are several new antifungal agents in development, and
      future studies will evaluate combination therapies to determine safety and
      efficacy.

PMID- 18628155
TI  - Invasive fungal infections in patients with hematologic malignancies: the next
      steps.

PMID- 18628156
TI  - Benefits of GM-CSF Versus Placebo or G-CSF in Reducing Chemotherapy-Induced
      Complications: A Systematic Review of the Literature.
AB  - Unlike granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage
      colony-stimulating factor (GM-CSF) is not approved for reducing the incidence or
      duration of chemotherapy-induced febrile neutropenia. However, some studies have
      been conducted in this setting. A systematic review assessing the efficacy of GM
      CSF versus placebo or G-CSF in reducing chemotherapy-induced febrile neutropenia
      and related complications was performed. Medline was reviewed for articles
      published between January 1987 and March 2003 that contained specific search
      terms. Explicit inclusion/exclusion criteria were developed for titles,
      abstracts, and articles. Two researchers reviewed (kappa>/= 0.7) and divided
      studies according to their evaluation of GM-CSF versus placebo or versus G-CSF.
      Nine studies were accepted: 6 randomized controlled trials compared GM-CSF versus
      placebo and 3 studies compared GM-CSF versus GCSF. Three placebo-controlled
      trials showed that GM-CSF was ineffective in reducing the risk of chemotherapy
      induced febrile neutropenia. The remaining 3 trials reported incidence of fever
      and not febrile neutropenia: 2 reported a significantly increased incidence of
      fever in the GM-CSF group, and 1 reported that more patients receiving placebo
      experienced fever compared with patients in the GMCSF group (P > 0.05). The 3
      studies comparing GM-CSF versus G-CSF reported fever as a primary outcome also.
      All 3 reported higher incidence of fever in the GM-CSF group (P < 0.05). Head-to
      head trials of G-CSF and GM-CSF in reducing chemotherapy-induced complications
      are lacking. Identified GM-CSF studies did not show significant reduction in
      febrile neutropenia and fever.

PMID- 18628157
TI  - The volume/outcome relationship in urologic cancer surgery.
AB  - There is growing evidence in the literature of the association between higher
      hospital and surgeon volume and better outcomes from high-risk surgical
      procedures. A Medline search of the literature from 1966 to 2004 was performed
      using the keywords "outcome," "urology," "neoplasms," "volume," "hospital
      volume," "surgeon volume," "prostatectomy," "cystectomy," "nephrectomy,"
      "prostate cancer," "bladder cancer," "kidney cancer," and "testis cancer." The
      relevant articles were reviewed and discussed in reference to each urologic
      cancer. Several studies have shown that higher hospital volume is associated with
      better outcomes for all urologic cancer surgeries. An association between
      postoperative mortality/morbidity and hospital and surgeon volumes was
      established. Individual surgeon volume is also a predictor of the quality and
      completeness of certain procedures such as radical prostatectomy. Long-term
      survival from cancer such as testicular cancer can be impacted by provider and
      institution volume. The evidence that highvolume hospitals have better outcomes
      from various types of urologic cancer surgery is increasing. The ultimate
      implication of these studies is that centralizing health care may yield better
      outcomes from urologic cancer surgeries. This is controversial and will have
      major health policy implications. Another approach would be to determine key
      factors that are the drivers behind better outcomes at high-volume centers and
      attempt to transfer those characteristics to lower-volume centers, thereby
      improving outcomes globally across all volume levels.

PMID- 18628158
TI  - Management of constipation in patients with cancer.
AB  - Constipation is highly prevalent in patients with cancer and is a source of
      tremendous suffering. The physiology of the gastrointestinal tract and the
      pathophysiology of constipation are being elucidated. Therapeutic agents include
      stool softeners, osmotic agents, stimulant laxatives, lubricants, and enemas.
      Synergism of these agents, which act through different mechanisms, is often
      required to successfully treat constipation. Selective serotonin agonists and
      peripherally acting opioid antagonists are being studied and may prove to be
      important additions to our pharmacologic armamentarium.

PMID- 18628159
TI  - Weekly administration of epoetin alfa improves cognition and quality of life in
      patients with breast cancer receiving chemotherapy.
AB  - Patients with breast cancer treated with adjuvant chemotherapy experience not
      only fatigue and menopausal symptoms but also documented cognitive dysfunction
      and reduced capacity to carry out activities of daily living. The role of epoetin
      alfa in improving cognition and functional capacity was assessed in a large
      randomized trial through patient self-reported outcomes. Patients with breast
      cancer (N = 354, adjuvant and metastatic) undergoing chemotherapy were randomized
      in a 1:1 ratio to receive epoetin alfa (40,000 IU once weekly) or the standard of
      care (SOC). Change in patient-reported Health Utilities Index Mark 3 (HUI3) from
      baseline to week 12 was compared between the epoetin alfa and SOC groups. In
      addition, correlations between the disease-nonspecific HUI3 utility scale and the
      cancer-specific quality of life instrument Functional Assessment of Cancer
      Therapy-Anemia (FACT-An) and Fatigue subscales were assessed. Epoetin alfa
      treatment significantly improved HUI3 scores compared with patients receiving SOC
      (P = 0.036). Three subscales within HUI3 were also significantly better for
      epoetin alfa-treated patients (emotion, P = 0.048; ambulation, P = 0.048; and
      cognition, P = 0.02). Moreover, a strong correlation (P = 0.0001) exists between
      the disease-nonspecific utility scale HUI3 and the disease-specific FACT-An and
      FACT-Fatigue scales in terms of overall scores and score changes. The findings of
      the study demonstrate for the first time in patients with breast cancer that
      epoetin alfa significantly enhances functional well-being, which translates into
      significantly better utility scores. In addition, epoetin alfa also significantly
      improved cognitive function of women undergoing chemotherapy, and this could have
      an important impact on their lives from a societal perspective.

PMID- 18628161
TI  - Improving clinical practice: the importance of guideline development.

PMID- 18628160
TI  - The correlation among patients and health care professionals in assessing
      functional status using the karnofsky and eastern cooperative oncology group
      performance status scales.
AB  - This study evaluated the correlation between Karnofsky performance status (KPS)
      and Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores
      assigned by doctors (MDs), nurses (RNs), radiation therapist (RTT), radiation
      therapy student (RTS), and patients (PTs) in assessing functional status of
      patients with cancer. Patients admitted to the general oncology and palliative
      care wards at our institution participated in the study. Data were gathered from
      survey forms completed by MDs, RNs, RTT, RTS, and PTs. The Spearman rank
      correlation coefficient was used to determine the extent of correlation between
      paired assessments. Thirty-six patients were enrolled in the study, 27 of whom
      were evaluable (17 men and 10 women), with a mean age of 57.7 years (range, 32-76
      years). The correlation for ECOG PS scores were MD/RTS = 0.81; MD/RN = 0.77;
      MD/RTT = 0.57; MD/PT = 0.64; PT/RN = 0.51; PT/RTT = 0.60; and PT/RTS = 0.64. The
      correlations for KPS scores were MD/RTS = 0.81; MD/RN = 0.74; MD/RTT = 0.67;
      MD/PT = 0.70; PT/RN = 0.60; PT/RTT = 0.79; and PT/RTS = 0.60. The findings
      demonstrate that patients can make valuable and reliable self-assessments as
      evidenced from the moderate to good degree of correlation of patient-assigned
      scores with those of health care professionals.

PMID- 18628162
TI  - Highlights from: Third Annual Future of Supportive Therapy in Oncology, San
      Francisco, CA; 27th Annual, San Antonio Breast Cancer Symposium, San Antonio, TX;
      46th Annual Meeting of the American Society of Hematology, San Diego, CA.

PMID- 18628163
TI  - Pegfilgrastim: recent advances in the prophylaxis of chemotherapy-induced
      neutropenia.

PMID- 18628165
TI  - Impact of erythropoietic agents on survival of anemic patients with cancer.

PMID- 18628164
TI  - Novel thrombopoetin mimetic agents with potential to ameliorate chemotherapy
      induced thrombocytopenia.

PMID- 18628166
TI  - Optimizing management of tumor lysis syndrome in adults with hematologic
      malignancies.
AB  - Tumor lysis syndrome (TLS), caused by the release of cellular components into the
      blood after rapid cell lysis, is a serious problem in patients with hematologic
      malignancies. It is characterized by hyperuricemia, hyperkalemia,
      hyperphosphatemia, and secondary hypocalcemia, with serious clinical consequences
      including renal failure and death. Although TLS may occur spontaneously, it is
      more commonly caused by the destruction of malignant cells by chemotherapy. The
      risk of developing TLS is influenced by a number of characteristics including the
      type of malignancy, the type and intensity of anticancer treatment, and the
      presence of preexisting conditions such as renal insufficiency. Particularly,
      high-risk patients who have malignancies with a high rate of cell turnover are
      highly sensitive to chemotherapy. The identification and prophylactic treatment
      of patients at high risk of developing TLS is key to the management of TLS. This
      review provides a summary of the pathogenesis of TLS, risk factors for TLS, its
      associated incidence and clinical consequences, and pharmacologic options for
      prevention and treatment.

PMID- 18628167
TI  - Patient selection and treatment of tumor lysis syndrome in adults with
      hematologic malignancies.

PMID- 18628168
TI  - A primer in prognostic and predictive models: development and validation of
      neutropenia risk models.
AB  - Prognostic or risk models can be used to identify risk factors that are
      associated with the outcome of interest or to accurately predict response to
      therapy. Increasingly, such models are playing a role in clinical oncology when
      selecting patients for more targeted therapy. Multivariate risk models require
      careful attention to accurate measurements, a priori selection of the primary
      outcomes and risk factors of interest, specification of data collection including
      any missing values, and assessment of collinearity and any confounding or effect
      modification. Recommendations for the design, conduct, analysis, and reporting of
      risk model studies in oncology are provided herein. Procedures for assessing
      model predictive performance or accuracy are discussed, including model
      discrimination, calibration, and power. An illustration of model development and
      validation is provided for a neutropenia risk model. The modeling procedure
      includes characterization of the population being studied, identification in
      advance of dependent or outcome variables and independent or risk factors,
      specification of the modeling plan including univariate and multivariate
      analyses, evaluation of the model predictive performance, and the procedure for
      validation of the model. Finally, there should be a plan for implementation and
      evaluation of the model in actual clinical practice. Prognostic or risk models
      are being developed and applied in a broad range of areas in clinical oncology.
      When properly developed and validated, such models are able to guide clinicians
      in the selection of patients who are at the greatest risk in order to target
      potentially toxic or expensive interventions in a more effective and cost
      effective manner.

PMID- 18628169
TI  - The role of methadone in the treatment of moderate to severe cancer pain.
AB  - The World Health Organization recommends a step-by-step approach to the
      management of chronic cancer pain, called the analgesic ladder. Traditionally,
      morphine has been the prototypical opioid for chronic cancer pain because there
      is no ceiling effect or upper limit and it is a naturally occurring pure mu
      opioid agonist. Occasionally, there are dose-limiting side effects and/or lack of
      efficacy. Opioid rotation is important because it improves analgesia and the side
      effect profile. Two principal reasons for failure of strong opioids are the
      presence of incident pain and/or neuropathic pain. Incident pain usually occurs
      in a patient with osseous metastases or another movement-related pain syndrome.
      Other reasons to rotate opioids are side effects such as intractable nausea and
      vomiting, sedation, dysphoria, delirium, and constipation, which are unresponsive
      to simple measures such as retitration, antiemetic agents, antipsychotic agents,
      psychostimulants, and laxatives. There are recent data that demonstrate that the
      accumulation of active metabolites in patients receiving common opioids such as
      morphine and hydromorphone are partly responsible for adverse effects. This
      premise has prompted clinicians and researchers to consider opioid rotation as a
      valid tool for cancer pain management to increase the probability of acceptable
      adverse effects with adequate analgesia. Methadone is an opioid agonist with a
      lack of known active metabolites, which are known to produce side effects with
      other opioids. Methadone has excellent bioavailability, making it a desirable
      analgesic agent for refractory types of cancer pain.

PMID- 18628170
TI  - Chemotherapy-induced emesis: quality of life and economic impact in the context
      of current practice in Canada.
AB  - In this study, we estimated the proportion of patients who experience
      chemotherapy-induced nausea and vomiting (CINV) in current practice and evaluated
      the impact of CINV on quality of life and cost in Canada. Patients receiving
      highly emetogenic chemotherapy were recruited from 4 Canadian oncology centers.
      Patients used diaries to record information on their activities, incidence of
      nausea and vomiting, and health resources consumed each day for 5 days following
      chemotherapy. They also completed the Functional Living Index-Emesis (FLIE)
      questionnaire and a health utility instrument before chemotherapy and 5 days
      later. Of the 323 patients recruited, 266 (82%) completed their diary. On day 1,
      26% of patients reported nausea or vomiting (acute emesis). From day 2 to day 5
      after chemotherapy, 44% reported nausea or vomiting (delayed emesis). Patients
      who experienced nausea or vomiting during the study period had a decrease in FLIE
      score of 22% and a decrease in health utility of 15%. Patients with nausea or
      vomiting reported an average of 19 hours per cycle during which they were unable
      to perform their normal activities. Also, friends or relatives spent an average
      of 10 hours helping these patients. Incremental medical costs per patient
      experiencing CINV were $61 Canadian. Including productivity losses, total
      incremental costs were $592 Canadian per patient. Despite use of antiemetics,
      CINV remains problematic, impacting the quality of life of patients with cancer
      and increasing costs.

PMID- 18628171
TI  - Tumor lysis syndrome in solid tumors.
AB  - Tumor lysis syndrome (TLS) consists of acute hyperuricemic nephropathy,
      hyperphosphatemia, hypocalcemia, hyperkalemia, and increased serum creatinine. It
      can be part of the disease presentation, especially in aggressive hematologic
      malignancies, or a part of the chemotherapy response. There are relatively few
      reports of TLS in solid tumors. Herein, we present 3 cases-1 small-cell lung
      cancer case and 2 breast cancer cases-that developed signs consistent with TLS
      upon initiation of treatment. Identified risk factors include disease bulk,
      aggressive growth, hepatic involvement, and pretreatment laboratory abnormalities
      such as elevated lactate dehydrogenase, uric acid, and creatinine. All 3 patients
      responded to hydration and allopurinol. One patient received rasburicase.
      Although the reported number of TLS cases associated with solid tumors is small,
      it may be that it is underdiagnosed or unsuspected in most situations. The
      purpose of this report is to alert clinicians to the possibility of TLS, even in
      solid tumors, so they can preemptively manage it.

PMID- 18628172
TI  - Impact of the multinational association of supportive care in cancer on
      supportive cancer therapy.

PMID- 18628173
TI  - Highlights from: The 41st Annual Meeting of the American Society of Clinical
      Oncology; Orlando, FL.

PMID- 18628174
TI  - Deferasirox (ICL670; Exjade(R)), a Novel Orally Available Iron Chelator for
      Correction of Transfusion-Associated Iron Overload.

PMID- 18628175
TI  - Role of psychostimulants in the management of cancer-related fatigue in patients
      with advanced cancer.

PMID- 18628176
TI  - Treatment of anemia with erythropoietic agents in patients with hematologic
      malignancies.
AB  - Anemia is common in patients with hematologic malignancies, occurring in up to
      70% of patients; it is associated with debilitating fatigue and weakness that
      negatively affect the ability of patients to conduct daily activities and cope
      with cancer. The severity of anemia in this population is dependent on the
      specific malignancy diagnosed, extent of disease, and the type and duration of
      chemotherapy received. Despite the well-known adverse consequences of anemia in
      patients with cancer, nearly half of patients with hematologic malignancies do
      not receive treatment for anemia. Clinical trials have demonstrated that
      treatment with erythropoietic agents (ie, epoetin alfa, epoetin beta, and
      darbepoetin alfa) in anemic patients with hematologic malignancies significantly
      increases hemoglobin (Hb) and reduces transfusion requirements. In addition,
      there is growing evidence to support the role of these agents in alleviating
      anemia-related symptoms and improving quality of life (QOL). Clinical practice
      guidelines issued by the National Comprehensive Cancer Network recommend
      erythropoietic therapy for patients receiving chemotherapy who have a Hb level
      </= 11 g/dL and symptoms or risk factors related to anemia. However, several
      trials of epoetin alfa therapy in patients with solid tumors or hematologic
      malignancies and mild-to-moderate anemia (Hb levels >/= 8 g/dL to </= 12 g/dL)
      receiving chemotherapy have demonstrated a positive effect on hematologic and QOL
      outcomes. Final results from a recent clinical trial evaluating the effects of
      earlier treatment with epoetin alfa on hematologic outcomes, QOL, health care
      resource utilization, and work/productivity in patients with mild anemia will
      provide further information on the most appropriate strategy for anemia treatment
      in this population.

PMID- 18628177
TI  - Supportive care of elderly patients with cancer.
AB  - The majority of cancers are more prevalent in individuals aged >/= 65 years than
      in younger patients, and supportive care is the key to treatment tolerance and
      quality of life for these individuals. This article examines the management of
      common complications of chemotherapy and pain in older patients with cancer. In
      accordance with the National Cancer Center Network guidelines, it is recommended
      that individuals aged >/= 65 years be treated prophylactically with filgrastim or
      pegfilgrastim for the prevention of neutropenic infections when challenged by
      chemotherapy of dose intensity comparable to that of CHOP (cyclophosphamide/
      doxorubicin/vincristine/prednisone) and that the levels of circulating hemoglobin
      be kept at >/= 12 g/dL. In addition, it is recommended that the dose of cytotoxic
      agents be adjusted to renal function and that low-toxicity treatment (ie,
      capecitabine in lieu of 5-fluorouracil [5-FU], pegylated liposomal doxorubicin in
      lieu of doxorubicin) be used when feasible and indicated. For the management of
      pain, the following principles are established: age is not an absolute hindrance
      to pain assessment; a number of instruments and the observation of pain behaviors
      are reliable even in patients with dementia; cyclooxygenase (COX)-2 inhibitors
      are preferable to COX-1 inhibitors for individuals with bleeding diathesis,
      peptic ulcer, and Helicobacter pylori gastritis; and opioids should be slowly
      titrated because the effectiveness and toxicity become less predictable with age.
      In conclusion, with individualized supportive care, the survival and quality of
      life of older patients with cancer may be improved.

PMID- 18628178
TI  - A combined analysis of average relative dose intensity in the chemotherapy of
      solid tumors with pegfilgrastim or filgrastim support.
AB  - A metaanalysis of 4 clinical studies that treated adult solid tumors with
      standard combination chemotherapy and growth factor support was conducted to
      study average relative dose intensity. All studies compared pegfilgrastim with
      filgrastim in a randomized, doubleblinded design. A total of 564 patients were
      included in the analyses: 291 who received pegfilgrastim and 273 who received
      filgrastim. For all cycles of treatment, the mean duration of filgrastim dosing
      was between 10 and 11 days, compared with 1 dose per cycle of pegfilgrastim.
      Median average dose intensities were between 99% and 100% of planned intensity in
      the pegfilgrastim and filgrastim groups. Across all studies, 96% of patients
      receiving pegfilgrastim and 95% of patients receiving filgrastim received an
      average relative dose intensity of >/= 85%. Less than 10% of patients in the
      pegfilgrastim and filgrastim groups experienced a dose delay, and < 5% of
      patients received a chemotherapy reduction. We conclude that the use of
      prophylactic growth factor support was associated with a high proportion of
      chemotherapy cycles that were delivered on schedule and at full dose.

PMID- 18628179
TI  - Survival-adjusted multiple-event analysis for the evaluation of treatment effects
      of zoledronic Acid in patients with bone metastases from solid tumors.
AB  - Bone metastasis causes significant pain and morbidity and is characterized by
      multiple skeletal-related events (SREs), including fractures, spinal cord
      compression, and the requirement for radiation or surgery to bone. Analysis of
      such a composite endpoint provides insight into the clinical impact of the
      disease. However, SREs typically occur in a complex pattern. Recently, zoledronic
      acid (4 mg) was approved for the treatment of bone metastases secondary to all
      solid tumors and primary bone lesions from multiple myeloma based on significant
      benefits from first-event and skeletal morbidity rate analyses. However, multiple
      event methods can provide information about the risk of SREs over the entire
      course of follow-up and address interpatient variation in event rates and
      temporal trends. Moreover, multiple-event methodology can adjust for survival,
      which has an effect on SRE incidence. Herein we present a survival-adjusted
      multiple-event analysis of the cumulative incidence of radiation to bone (a
      homogenous endpoint) and SREs (a composite endpoint) in 3 large, randomized
      clinical trials of zoledronic acid (4 mg) in patients with prostate cancer, lung
      cancer and other solid tumors, or breast cancer. In patients with prostate
      cancer, zoledronic acid significantly reduced the cumulative incidence of SREs
      compared with placebo (P = 0.002) as it did among patients with lung cancer and
      other solid tumors (P = 0.025). In patients with breast cancer, zoledronic acid
      significantly reduced the cumulative incidence of SREs compared with pamidronate
      90 mg over 25 months (P = 0.050). These results are consistent with those
      obtained using established methods, supporting the validity of the survival
      adjusted cumulative mean function for assessing benefits during bisphosphonate
      therapy.

PMID- 18628180
TI  - Sex differences in patients who have cancer with mild anemia: symptom burden and
      quality of life.
AB  - The same criterion for mild anemia (10 < hemoglobin [Hgb]<12 g/dL) has been used
      for male and female patients. Mild anemia is associated with greater symptom
      burden and reduced quality of life (QOL). We compared male and female patients
      who have mild anemia with each other and with their respective normal groups.
      Patients (N = 3553) from a community oncology database were sorted by sex and Hgb
      level into 3 anemic and 2 normal groups: men with 10 </= Hgb <12 g/dL, men with
      12 </= Hgb <14 g/dL, women with 10 </= Hgb <12 g/dL, men with Hgb >/= 14 g/dL,
      and women with Hgb >/= 12 g/dL. Patients receiving chemotherapy (< 30 days)
      and/or growth factor (< 60 days) were excluded. Each case provided same-day
      scores on the Cancer Care Monitor, a validated measure of symptom burden,
      functioning, and health-related QOL comprising 7 scales. Compared with respective
      normal groups, male and female patients with mild anemia showed greater symptom
      burden, lower functioning, and worse QOL (P <0.05). Compared with normal men and
      women, patients with mild anemia showed clinically significant differences in
      terms of effect size (Cohen's d, 0.11- 0.91). Men with 10 </= Hgb <12 g/dL were
      significantly more impaired and had worse QOL than men with 12 </= Hgb <14 g/dL
      or women with 10 </= Hgb <12 g/dL. Impact of mild anemia on QOL is significant,
      and treating men and women by the same standards (Hgb level < 12 g/dL) is likely
      incorrect. Mild anemia may be undertreated, especially for men with 12 </= Hgb
      <14 g/dL.

PMID- 18628181
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18628182
TI  - New strategies for the treatment of chemotherapy-induced diarrhea.

PMID- 18628183
TI  - Rasburicase for prevention of hyperuricemia and tumor lysis syndrome.

PMID- 18628184
TI  - Immunomodulation: the role of hematopoietic cytokines.
AB  - Hematopoietic cytokines have been used primarily as supportive care for patients
      undergoing cytotoxic chemotherapy or hematopoietic progenitor mobilization.
      Although the commonly used agents, granulocyte colony-stimulating factor and
      granulocytemacrophage colony-stimulating factor (GM-CSF), have been used
      interchangeably, it is clear that they have different effects on immune function
      and immune priming. GM-CSF has been used for some time as a vaccine adjuvant
      agent because of its activity on monocytes and dendritic cells. In order to
      capitalize on the immune activation effects of GM-CSF, numerous groups have
      transduced the GM-CSF gene into tumor cells in an effort to recruit local
      inflammatory cells and cytokines to the site of vaccination. Additionally, GM-CSF
      alone has been demonstrated to have activity for patients with high-risk melanoma
      and hormone-refractory prostate cancer. This article discusses some of the immune
      enhancing and suppressive activities of the hematopoietic cytokines, with
      particular focus on the immunomodulatory effects of GM-CSF, both in the context
      of single-agent therapy for solid tumors as well as in the context of dendritic
      cell modulation during therapy for hematopoietic malignancies.

PMID- 18628185
TI  - Inhibiting substance p pathway for prevention of chemotherapy-induced emesis:
      preclinical data, clinical trials of neurokinin-1 receptor antagonists.
AB  - Neurokinin-1 (NK-1) receptor antagonists are a new class of antiemetic agents
      that have activity in controlling cisplatin-induced acute and delayed emesis.
      Preclinical data in animal models show that the NK-1 receptor antagonists have
      broad antiemetic activity. The NK-1 receptor antagonists have activity in
      controlling emesis induced by peripherally acting and centrally acting emetogens,
      suggesting a mechanism of action at multiple sites. The effects at central and
      peripheral sites to control acute and delayed emesis cannot be determined at this
      time based on available studies. When added to a standard regimen of a 5
      hydroxytryptamine-3 (5- HT3) receptor antagonist and dexamethasone, the NK-1
      receptor antagonists improve control of acute emesis. The NK-1 receptor
      antagonists improve delayed emesis compared with placebo, and when used in
      combination with dexamethasone, compared with dexamethasone alone. Acute and
      delayed nausea may also be improved by the NK-1 receptor antagonists when they
      are used in combination with a 5-HT3 receptor antagonist and dexamethasone
      prechemotherapy or with daily dosing for 5 days after chemotherapy. The current
      data suggest that the mechanism of action of the NK-1 receptor antagonists
      appears to be different from that of the 5-HT3 receptor antagonists. Future
      studies may consider using NK-1 receptor antagonists with moderately emetogenic
      chemotherapy as well as bone marrow transplantation.

PMID- 18628186
TI  - Recent developments in cancer pain assessment and management.
AB  - Pain and other symptoms of advanced cancer are not treated effectively yet. This
      review of the literature discusses the needs and latest research findings about
      pain symptom assessment and management in palliative care. Pain assessment scores
      should not be followed blindly by a rigid therapeutic regimen. Instead, the
      health care provider should carefully consider the wide spectrum of possible
      underlying pain mechanisms. Unidimensional pain rating scales will not detect the
      impact of affective dimensions on pain expression as accurately as
      multidimensional rating scales that include various symptoms. Besides assessment
      tools like numeric rating scales or visual analogue scales, tools now frequently
      used in the daily clinical setting include the Edmonton Symptom Assessment
      System, the Mini Mental State Examination, and the CAGE questionnaire (Cutting
      down, Annoyance by criticism, Guilty feeling, and Eye-openers). Recent
      developments and findings in cancer pain management are illustrated by (1) the
      use of opioids like morphine, oxycodone, fentanyl, and especially methadone
      (which has been used increasingly as a secondline drug for opioid-resistant and
      neuropathic pain, and also for its low cost, long-acting nature, and low side
      effect probability, especially in patients with renal failure resulting from the
      lack of active metabolites); (2) the use of adjuvant therapeutic agents like
      gabapentin, donepezil, dextromethorphan, and thalidomide; (3) the impact of the
      immune system on pain, with a concept of targeting immune cells that contain
      opioids to potentially enhance opioid production, the migration of these cells to
      tissue lesions, and the release of opioids at the peripheral site to achieve
      increased peripheral analgesia; and (4) approaches to pain imaging as well as the
      newly introduced interventions of vertebroplasty and kyphoplasty.

PMID- 18628187
TI  - Prevention and treatment of salivary gland hypofunction related to head and neck
      radiation therapy and chemotherapy.
AB  - Radiation therapy and chemotherapy for malignant tumors in the head and neck
      region are inevitably associated with injury to oral tissues, including the
      salivary glands. This often results in salivary gland hypofunction. Until now
      there has been no effective method of preventing damage caused by cancer
      therapies. Although not yet supported by sufficient evidence, there are some
      clinical trials indicating a potential benefit from radical scavengers and saliva
      stimulants. Other developments are in gene transfer to regain salivary gland
      function and stem cell transplantation to regenerate a diseased salivary gland.
      While irradiation on salivary gland tissue is irreversible to a large extent,
      hyposalivation associated with chemotherapy is usually less severe and
      reversible. In case of significant residual secretory capacity, supportive care
      is indicated. These patients are advised to stimulate their salivary glands by
      mechanical or gustatory stimuli. Alternatively, salivary flow can be stimulated
      by cholinergic stimulation (eg, pilocarpine or cevimeline). In the case of little
      or no residual capacity, palliative treatment is the only option. In such
      patients, nocturnal oral dryness can be alleviated by spraying oral surfaces with
      water or by applying a saliva substitute, particularly a substitute with gellike
      properties. During the day, the application of mouthwashes and saliva substitutes
      is indicated if moistening of oral surfaces with water is not sufficient. Recent
      developments are focusing on bioactive saliva substitutes and mouthwashes
      containing antimicrobial peptides to protect oral tissues against microbial
      colonization and to suppress or cure mucosal and gingival inflammation.

PMID- 18628189
TI  - Exploring the breadth of supportive cancer care issues.

PMID- 18628188
TI  - Decision-making role preferences of patients receiving adjuvant cancer treatment:
      a university of Rochester cancer center community clinical oncology program.
AB  - This study examined patients' preferences for involvement in treatment decision
      making. This was a multisite survey study of 1014 patients diagnosed with a
      variety of cancers. Patients' treatment decisions, role preferences, and
      characteristics were assessed with a questionnaire administered at the time of
      their first visit with a medical or radiation oncologist. The data showed that
      35.7% preferred passive roles, 43.7% preferred shared roles, and 20.3% preferred
      active roles in decision-making. Bivariate analyses indicated that patients with
      a college education or in professional or managerial occupations preferred more
      active roles in decisionmaking compared with other patients. Similarly, men with
      prostate cancer and women with breast cancer, compared with other patients, also
      preferred more involvement in decision-making. Age was not associated with
      decision-making role preferences. Avoidant and fatalistic coping were associated
      with a passive decision-making role. Multinomial logistic regression analysis
      found that patients in professional/managerial occupations preferred a shared
      role (odds ratio [OR], 1.6; CI, 1.2-2.4) or an active role (OR, 2.3; CI, 1.5-3.5)
      compared with patients in other occupations. Patients with prostate or breast
      cancer preferred shared (OR, 2.3; CI, 1.6-3.2) or active roles (OR, 1.8; CI, 1.2
      2.8) compared with patients with other diagnoses. Patients who scored higher on
      the Mental Adjustment to Cancer fatalism scale were less likely to prefer shared
      (OR, 0.94; CI, 0.89-0.99) or active roles (OR, 0.90; CI, 0.84- 0.96) compared
      with patients with a less fatalistic orientation. Decision-making role
      preferences were influenced by multiple factors. Most patients wanted a shared or
      active role in treatment decision-making. Our results suggest that some patients
      may require encouragement to take a shared or active role in decision-making.

PMID- 18628190
TI  - Highlights from: The 46th Annual Meeting of the American Society of Hematology;
      San Diego, CA.

PMID- 18628191
TI  - Palifermin is efficacious in reducing oral mucositis induced by intensive cancer
      therapy.

PMID- 18628192
TI  - Role of prophylactic quinolones in reducing febrile neutropenia in patients
      undergoing myelosuppressive chemotherapy.

PMID- 18628193
TI  - An overview of the management of infection and febrile neutropenia in patients
      with cancer.
AB  - Infections remain a frequent complication in the care of patients with cancer,
      especially in those patients who sustain neutropenia during their disease course.
      Risk factors for infection in these patients include not only therapy-related
      myelosuppression, but also immune defects inherent to the underlying disease
      process. The bacterial spectrum of infection in these patients has changed over
      the decades, with infections caused by Gram-positive organisms now being more
      common than those infections because of Gramnegative isolates. Candida and
      Aspergillus species remain the most common causes of fungal infections. The
      approach to the antimicrobial management of these patients has been aided by the
      development of guidelines for care by the Infectious Disease Society of America
      (IDSA). The advent of new antimicrobial agents, especially antifungals, has
      impacted the care of these patients. In this article, the risk factors for
      infection, spectrum of infection, and approaches to antimicrobial management will
      be reviewed.

PMID- 18628194
TI  - Moving beyond febrile neutropenia.

PMID- 18628195
TI  - Supportive care aspects of vertebroplasty in patients with cancer.
AB  - Minimally invasive vertebroplasty involves the percutaneous injection of
      polymethylmethacrylate bone cement into a fractured vertebral body. Although most
      frequently performed for osteoporotic compression fractures, vertebroplasty has
      also been very effective in the palliation of back pain secondary to osteolytic
      metastases and myeloma bone disease. The mechanism of pain relief is unclear;
      however, stabilization of microfractures and restoration of vertebral body
      strength is the leading theory. The decision to perform vertebroplasty is made
      after multiple factors are considered, including clinical presentation, medical
      fitness, functional capacity, tumor type, location and extent of disease,
      anticipated radiation sensitivity, and quality of life. Cement extravasation
      beyond the vertebral body is the most frequent complication; however, it is
      asymptomatic in the vast majority of patients. In the cancer setting,
      vertebroplasty is used as an adjunct to other standard treatments, including
      medical therapy, radiation therapy, chemotherapy, and surgery. In well-selected
      patients, vertebroplasty offers rapid relief of axial back pain and the potential
      for improved function.

PMID- 18628196
TI  - A brief update on the biomechanisms underlying cement injection and leakage in
      vertebroplasty.

PMID- 18628197
TI  - Impact of severe acute respiratory syndrome on patient access to palliative
      radiation therapy.
AB  - This study evaluated the impact of the severe acute respiratory syndrome (SARS)
      epidemic on access and utilization of palliative radiation therapy (RT) at a
      single institution using a retrospective chart review. A total of 649 patients
      seen between January and May 2002 and between January and May 2003 were
      evaluated. Treatment characteristics and waiting times were recorded. March 20 to
      May 30, 2003, was defined as the peak period of incidence and was compared with
      the same period in 2002. During the SARS epidemic, there was a 21% decrease in
      the number of patient consultations and a 15% reduction in the number of patients
      treated with RT. There was no significant change in the tumor type or reason for
      referral. Short fractionation schedules were employed for 35% of treated patients
      compared with 34% in 2002. Patient waiting times between referral and treatment
      decreased during the period of interest, from 16 days to 8 days (P = 0.021). This
      study demonstrates a reduction in palliative RT services that is similar in
      magnitude to decreases observed in other essential cancer services during the
      SARS epidemic. Use of single-fraction RT and delayed follow-up visits may help to
      minimize hospital transfers and visits in the event of future infectious disease
      outbreaks.

PMID- 18628198
TI  - A randomized, multicenter, open-label comparison of the antiemetic efficacy of
      dolasetron versus ondansetron for the prevention of nausea and vomiting during
      high-dose myeloablative chemotherapy.
AB  - This study assessed the efficacy and safety of dolasetron compared with
      ondansetron for the prevention of nausea and vomiting during high-dose
      myeloablative chemotherapy followed by peripheral blood stem cell support. Twenty
      centers randomized 197 patients to receive dolasetron 100 mg intravenously (I.V.)
      followed 8-12 hours later by a single oral dose of dolasetron 100 mg or
      ondansetron 32 mg I.V., followed 8-12 hours later by a single oral dose of
      ondansetron 8 mg during high-dose chemotherapy (HDC) regimens for breast cancer
      (n = 96; 48.7%), non-Hodgkin's lymphoma (n = 83; 42.1%), or Hodgkin's disease (n
      = 18; 9.1%). All patients received a daily I.V. bolus of dexamethasone 10 mg with
      study antiemetic agents and a continuous infusion of diphenhydramine, lorazepam,
      and dexamethasone (ie, BAD pump) throughout the course of the study, with patient
      controlled on-demand bolus doses as needed. After completing a daily diary of
      emetic episodes and rescue medication use, 164 of 197 patients were evaluable.
      Total plus complete responses (no emesis, no nausea, no rescue) over the entire
      study period were achieved in 45.7% and 46.9% of patients on the dolasetron and
      ondansetron arms, respectively. Dolasetron and ondansetron were well-tolerated.
      This study demonstrates that dolasetron and ondansetron are equally safe and
      effective in the prevention of nausea and vomiting associated with HDC (P =
      0.955).

PMID- 18628199
TI  - Single-Dose Prevention or Short-Term Treatment with Fibroblast Growth Factor-20
      (CG53135-05)Reduces the Severity and Duration of Oral Mucositis.
AB  - Oral mucositis (OM) is a treatment-limiting condition associated with
      myelosupressive chemotherapy and radiation therapy. The objective of this study
      was to evaluate the activity of recombinant human fibroblast growth factor-20
      (FGF-20 or CG53135-05) in the prevention and treatment of OM in experimental
      animals. Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60
      mg/kg) on days -4 and -2, followed by targeted irradiation with 30 Gy on day 0.
      Oral mucositis was scored every other day using severity scores of 0-5. To test
      for prevention of OM, animals received varying doses of FGF-20 on day 1 or days 1
      and 2 after irradiation before the development of symptoms. To test the effects
      of FGF-20 on established mucositis, animals were allowed to develop early OM
      (score of 2) before treatment initiation. Animals then received FGF-20 by
      intraperitoneal (i.p.) administration (12 mg/kg) for 1, 2, 3, or 4 consecutive
      days. When prevention of OM was tested, administration of FGF-20 (12 mg/kg i.p.)
      on day 1 or days 1 and 2 resulted in significant reduction in duration of severe
      OM to 26% (P < 0.003) or 29.4% (P <0.018) of cumulative days, respectively,
      compared with untreated control animals, which spent 40.2% of cumulative days
      with OM scores >/= 3. When the effects of FGF-20 on established mucositis were
      tested, treatment of animals with FGF-20 for 2, 3, or 4 consecutive days resulted
      in significant reduction of severe OM to 27.4%, 29.2%, or 18.5% of days,
      respectively, compared with vehicle-treated control animals, which spent 41.1% of
      cumulative days with OM scores >/=3 (P < 0.05). These findings support the
      utility of FGF-20 as a single-dose agent in the prevention of OM. In addition,
      the positive effects of FGF-20 on established mucositis may permit treatment of
      patients with OM who may not benefit from prophylactic agents.

PMID- 18628200
TI  - The influence of mesoscale porosity on cortical bone anisotropy. Investigations
      via asymptotic homogenization.
AB  - Recently, the mesoscale of cortical bone has been given particular attention in
      association with novel experimental techniques such as nanoindentation, micro
      computed X-ray tomography and quantitative scanning acoustic microscopy (SAM). A
      need has emerged for reliable mathematical models to interpret the related
      microscopic and mesoscopic data in terms of effective elastic properties. In this
      work, a new model of cortical bone elasticity is developed and used to assess the
      influence of mesoscale porosity on the induced anisotropy of the material. Only
      the largest pores (Haversian canals and resorption cavities), characteristic of
      the mesoscale, are considered. The input parameters of the model are derived from
      typical mesoscale experimental data (e.g. SAM data). We use the method of
      asymptotic homogenization to determine the local effective elastic properties by
      modelling the propagation of low-frequency elastic waves through an idealized
      material that models the local mesostructure. We use a novel solution of the cell
      problem developed by Parnell & Abrahams. This solution is stable for the
      physiological range of variation of mesoscopic porosity and elasticity found in
      bone. Results are computed efficiently (in seconds) and the solutions can be
      implemented easily by other workers. Parametric studies are performed in order to
      assess the influence of mesoscopic porosity, the assumptions regarding the
      material inside the mesoscale pores (drained or undrained bone) and the shape of
      pores. Results are shown to be in good qualitative agreement with existing
      schemes and we describe the potential of the scheme for future use in modelling
      more complex microstructures for cortical bone. In particular, the scheme is
      shown to be a useful tool with which to predict the qualitative changes in
      anisotropy due to variations in the structure at the mesoscale.

PMID- 18628201
TI  - Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor
      site 4 and trapping the domain ii voltage sensor in the closed configuration.
AB  - Peptide toxins with high affinity, divergent pharmacological functions, and
      isoform-specific selectivity are powerful tools for investigating the structure
      function relationships of voltage-gated sodium channels (VGSCs). Although a
      number of interesting inhibitors have been reported from tarantula venoms, little
      is known about the mechanism for their interaction with VGSCs. We show that
      huwentoxin-IV (HWTX-IV), a 35-residue peptide from tarantula Ornithoctonus huwena
      venom, preferentially inhibits neuronal VGSC subtypes rNav1.2, rNav1.3, and
      hNav1.7 compared with muscle subtypes rNav1.4 and hNav1.5. Of the five VGSCs
      examined, hNav1.7 was most sensitive to HWTX-IV (IC(50) approximately 26 nM).
      Following application of 1 microm HWTX-IV, hNav1.7 currents could only be
      elicited with extreme depolarizations (>+100 mV). Recovery of hNav1.7 channels
      from HWTX-IV inhibition could be induced by extreme depolarizations or moderate
      depolarizations lasting several minutes. Site-directed mutagenesis analysis
      indicated that the toxin docked at neurotoxin receptor site 4 located at the
      extracellular S3-S4 linker of domain II. Mutations E818Q and D816N in hNav1.7
      decreased toxin affinity for hNav1.7 by approximately 300-fold, whereas the
      reverse mutations in rNav1.4 (N655D/Q657E) and the corresponding mutations in
      hNav1.5 (R812D/S814E) greatly increased the sensitivity of the muscle VGSCs to
      HWTX-IV. Our data identify a novel mechanism for sodium channel inhibition by
      tarantula toxins involving binding to neurotoxin receptor site 4. In contrast to
      scorpion beta-toxins that trap the IIS4 voltage sensor in an outward
      configuration, we propose that HWTX-IV traps the voltage sensor of domain II in
      the inward, closed configuration.

PMID- 18628202
TI  - Essential role for uncoupling protein-3 in mitochondrial adaptation to fasting
      but not in fatty acid oxidation or fatty acid anion export.
AB  - Uncoupling protein-3 (UCP3) is a mitochondrial inner membrane protein expressed
      most abundantly in skeletal muscle and to a lesser extent in heart and brown
      adipose tissue. Evidence supports a role for UCP3 in fatty acid oxidation (FAO);
      however, the underlying mechanism has not been explored. In 2001 we proposed a
      role for UCP3 in fatty acid export, leading to higher FAO rates (Himms-Hagen, J.,
      and Harper, M. E. (2001) Exp. Biol. Med. (Maywood) 226, 78-84). Specifically,
      this widely held hypothesis states that during elevated FAO rates, UCP3 exports
      fatty acid anions, thereby maintaining mitochondrial co-enzyme A availability;
      reactivation of exported fatty acid anions would ultimately enable increased FAO.
      Here we tested mechanistic aspects of this hypothesis as well as its functional
      implications, namely increased FAO rates. Using complementary mechanistic
      approaches in mitochondria from wild-type and Ucp3(-/-) mice, we find that UCP3
      is not required for FAO regardless of substrate type or supply rate covering a 20
      fold range. Fatty acid anion export and reoxidation during elevated FAO, although
      present in skeletal muscle mitochondria, are independent of UCP3 abundance.
      Interestingly, UCP3 was found to be necessary for the fasting-induced enhancement
      of FAO rate and capacity, possibly via mitigated mitochondrial oxidative stress.
      Thus, although our observations indicate that UCP3 can impact FAO rates, the
      mechanistic basis is not via an integral function for UCP3 in the FAO machinery.
      Overall our data indicate a function for UCP3 in mitochondrial adaptation to
      perturbed cellular energy balance and integrate previous observations that have
      linked UCP3 to reduced oxidative stress and FAO.

PMID- 18628203
TI  - A rotor-stator cross-link in the F1-ATPase blocks the rate-limiting step of
      rotational catalysis.
AB  - The F(0)F(1)-ATP synthase couples the functions of H(+) transport and ATP
      synthesis/hydrolysis through the efficient transmission of energy mediated by
      rotation of the centrally located gamma, epsilon, and c subunits. To understand
      the gamma subunit role in the catalytic mechanism, we previously determined the
      partial rate constants and devised a minimal kinetic model for the rotational
      hydrolytic mode of the F(1)-ATPase enzyme that uniquely fits the pre-steady state
      and steady state data ( Baylis Scanlon, J. A., Al-Shawi, M. K., Le, N. P., and
      Nakamoto, R. K. (2007) Biochemistry 46, 8785-8797 ). Here we directly test the
      model using two single cysteine mutants, betaD380C and betaE381C, which can be
      used to reversibly inhibit rotation upon formation of a cross-link with the
      conserved gammaCys-87. In the pre-steady state, the gamma-beta cross-linked
      enzyme at high Mg.ATP conditions retained the burst of hydrolysis but was not
      able to release P(i). These data show that the rate-limiting rotation step,
      k(gamma), occurs after hydrolysis and before P(i) release. This analysis provides
      additional insights into how the enzyme achieves efficient coupling and
      implicates the betaGlu-381 residue for proper formation of the rate-limiting
      transition state involving gamma subunit rotation.

PMID- 18628204
TI  - GABPbeta2 is dispensible for normal lymphocyte development but moderately affects
      B cell responses.
AB  - GA-binding protein (GABP) is the only Ets family transcription factor that
      functions as a heterodimer. The GABPalpha subunit binds to DNA, and the GABPbeta
      subunit possesses the ability to transactivate target genes. Inactivation of
      GABPalpha caused embryonic lethality and defective lymphocyte development and
      immune responses. There are 3 isoforms of the GABPbeta subunit, but whether they
      have distinct functions has not been addressed. In this study, we selectively
      ablated the expression of GABPbeta2 using a gene trap strategy. GABPbeta2
      deficient mice were viable and had normal T and B cell development, suggesting
      that loss of GABPbeta2 is compensated for by other GABPbeta isoforms during these
      processes. GABPbeta2-deficient T cells can be activated and proliferate similarly
      to wild-type controls. In contrast, B cells lacking GABPbeta2 showed 2-3-fold
      increases in proliferation in response to B cell receptor stimulation. In
      addition, GABPbeta2-deficient mice exhibited moderately increased antibody
      production and germinal center responses when challenged with T-dependent
      antigens. These results indicate that albeit GABPbeta isoforms are redundant in
      lymphocyte development, GABPbeta2 has a distinct role in restraining B cell
      expansion and humoral responses.

PMID- 18628205
TI  - Molecular control of phenoloxidase-induced melanin synthesis in an insect.
AB  - The melanization reaction induced by activated phenoloxidase in arthropods must
      be tightly controlled because of excessive formation of quinones and excessive
      systemic melanization damage to the hosts. However, the molecular mechanism by
      which phenoloxidase-induced melanin synthesis is regulated in vivo is largely
      unknown. It is known that the Spatzle-processing enzyme is a key enzyme in the
      production of cleaved Spatzle from pro-Spatzle in the Drosophila Toll pathway.
      Here, we provide biochemical evidence that the Tenebrio molitor Spatzle
      processing enzyme converts both the 79-kDa Tenebrio prophenoloxidase and Tenebrio
      clip-domain SPH1 zymogen to an active melanization complex. This complex,
      consisting of the 76-kDa Tenebrio phenoloxidase and an active form of Tenebrio
      clip-domain SPH1, efficiently produces melanin on the surface of bacteria, and
      this activity has a strong bactericidal effect. Interestingly, we found the
      phenoloxidase-induced melanization reaction to be tightly regulated by Tenebrio
      prophenoloxidase, which functions as a competitive inhibitor of melanization
      complex formation. These results demonstrate that the Tenebrio Toll pathway and
      the melanization reaction share a common serine protease for the regulation of
      these two major innate immune responses.

PMID- 18628206
TI  - ERp16, an endoplasmic reticulum-resident thiol-disulfide oxidoreductase:
      biochemical properties and role in apoptosis induced by endoplasmic reticulum
      stress.
AB  - We have characterized the properties and putative role of a mammalian thioredoxin
      like protein, ERp16 (previously designated ERp18, ERp19, or hTLP19). The
      predicted amino acid sequence of the 172-residue human protein contains an NH(2)
      terminal signal peptide, a thioredoxin-like domain with an active site motif
      (CGAC), and a COOH-terminal endoplasmic reticulum (ER) retention sequence (EDEL).
      Analyses indicated that the mature protein (comprising 146 residues) is generated
      by cleavage of the 26-residue signal peptide and is localized in the lumen of the
      ER. Biochemical experiments with the recombinant mature protein revealed it to be
      a thioldisulfide oxidoreductase. Its redox potential was about -165 mV; its
      active site cysteine residue Cys(66) was nucleophilic with a pK(a) value of
      approximately 6.6; it catalyzed the formation, reduction, and isomerization of
      disulfide bonds, with the unusual CGAC active site motif being responsible for
      these activities; and it existed as a dimer and underwent a redox-dependent
      conformational change. The observations that the redox potential of ERp16 (-165
      mV) was within the range of that of the ER (-135 to -185 mV) and that ERp16
      catalyzed disulfide isomerization of scrambled ribonuclease A suggest a role for
      ERp16 in protein disulfide isomerization in the ER. Expression of ERp16 in HeLa
      cells inhibited the induction of apoptosis by agents that elicit ER stress,
      including brefeldin A, tunicamycin, and dithiothreitol. In contrast, expression
      of a catalytically inactive mutant of ERp16 potentiated such apoptosis, as did
      depletion of ERp16 by RNA interference. Our results suggest that ERp16 mediates
      disulfide bond formation in the ER and plays an important role in cellular
      defense against prolonged ER stress.

PMID- 18628207
TI  - Vitamin D3 induces autophagy of human myeloid leukemia cells.
AB  - Vitamin D3 causes potent suppression of various cancer cells; however,
      significant supraphysiological concentrations of this compound are required for
      antineoplastic effects. Current combinatorial therapies with vitamin D3 are
      restricted to differentiation effects. It remains uncertain if autophagy is
      involved in vitamin D3 inhibition on leukemia cells. Here we show that besides
      triggering differentiation and inhibiting apoptosis, which was previously known,
      vitamin D3 triggers autophagic death in human myeloid leukemia cells. Inhibiting
      differentiation does not efficiently diminish vitamin D3 suppression on leukemia
      cells. Vitamin D3 up-regulates Beclin1, which binds to class III
      phosphatidylinositol 3-kinase to trigger autophagy. Vitamin D3 phosphorylates Bad
      in its BH3 domain, resulting in disassociation of the apoptotic Bad-Bcl-xL
      complex and association of Bcl-xL with Beclin1 and ultimate suppression of
      apoptotic signaling. Knockdown of Beclin1 eliminates vitamin D3-induced autophagy
      and inhibits differentiation but activates apoptosis, suggesting that Beclin1 is
      required for both autophagy and differentiation, and autophagy cooperates with
      differentiation but excludes apoptosis, in which Beclin1 acts as an interface for
      these three different cascades. Moreover, additional up-regulation of autophagy,
      but not apoptosis, dramatically improves vitamin D3 inhibition on leukemia cells.
      These findings extend our understanding of the action of vitamin D3 in
      antineoplastic effects and the role of Beclin1 in regulating multiple cellular
      cascades and suggest a potentially promising strategy with a significantly better
      antileukemia effect.

PMID- 18628208
TI  - Hepatocyte growth factor/c-MET axis-mediated tropism of cord blood-derived
      unrestricted somatic stem cells for neuronal injury.
AB  - An under-agarose chemotaxis assay was used to investigate whether unrestricted
      somatic stem cells (USSC) that were recently characterized in human cord blood
      are attracted by neuronal injury in vitro. USSC migrated toward extracts of post
      ischemic brain tissue of mice in which stroke had been induced. Moreover,
      apoptotic neurons secrete factors that strongly attracted USSC, whereas necrotic
      and healthy neurons did not. Investigating the expression of growth factors and
      chemokines in lesioned brain tissue and neurons and of their respective receptors
      in USSC revealed expression of hepatocyte growth factor (HGF) in post-ischemic
      brain and in apoptotic but not in necrotic neurons and of the HGF receptor c-MET
      in USSC. Neuronal lesion-triggered migration was observed in vitro and in vivo
      only when c-MET was expressed at a high level in USSC. Neutralization of the
      bioactivity of HGF with an antibody inhibited migration of USSC toward neuronal
      injury. This, together with the finding that human recombinant HGF attracts USSC,
      document that HGF signaling is necessary for the tropism of USSC for neuronal
      injury. Our data demonstrate that USSC have the capacity to migrate toward
      apoptotic neurons and injured brain. Together with their neural differentiation
      potential, this suggests a neuroregenerative potential of USSC. Moreover, we
      provide evidence for a hitherto unrecognized pivotal role of the HGF/c-MET axis
      in guiding stem cells toward brain injury, which may partly account for the
      capability of HGF to improve function in the diseased central nervous system.

PMID- 18628209
TI  - Neuropilin-1-VEGFR-2 complexing requires the PDZ-binding domain of neuropilin-1.
AB  - Vascular endothelial growth factor (VEGF) acts as a hierarchically high switch of
      the angiogenic cascade by interacting with its high affinity VEGF receptors and
      with neuropilin co-receptors. VEGF(165) binds to both Neuropilin-1 (NP-1) and
      VEGFR-2, and it is believed that ligand binding forms an extracellular bridge
      between both molecules. This leads to complex formation, thereby enhancing VEGFR
      2 phosphorylation and subsequent signaling. We found that inhibition of VEGF
      receptor (VEGFR) phosphorylation reduced complex formation between NP-1 and VEGFR
      2, suggesting a functional role of the cytoplasmic domain of VEGFR-2 for complex
      formation. Correspondingly, deleting the PDZ-binding domain of NP-1 decreased
      complex formation, indicating that extracellular VEGF(165) binding is not
      sufficient for VEGFR-2-NP-1 interaction. Synectin is an NP-1 PDZ-binding domain
      interacting molecule. Experiments in Synectin-deficient endothelial cells
      revealed reduced VEGFR-2-NP-1 complex formation, suggesting a role for Synectin
      in VEGFR-2-NP-1 signaling. Taken together, the experiments have identified a
      novel mechanism of NP-1 interaction with VEGFR-2, which involves the cytoplasmic
      domain of NP-1.

PMID- 18628210
TI  - Modified sympathetic nerve system activity with overexpression of the voltage
      dependent calcium channel beta3 subunit.
AB  - N-type voltage-dependent calcium channels (VDCCs) play determining roles in
      calcium entry at sympathetic nerve terminals and trigger the release of the
      neurotransmitter norepinephrine. The accessory beta3 subunit of these channels
      preferentially forms N-type channels with a pore-forming CaV2.2 subunit. To
      examine its role in sympathetic nerve regulation, we established a beta3
      overexpressing transgenic (beta3-Tg) mouse line. In these mice, we analyzed
      cardiovascular functions such as electrocardiography, blood pressure,
      echocardiography, and isovolumic contraction of the left ventricle with a
      Langendorff apparatus. Furthermore, we compared the cardiac function with that of
      beta3-null and CaV2.2 (alpha1B)-null mice. The beta3-Tg mice showed increased
      expression of the beta3 subunit, resulting in increased amounts of CaV2.2 in
      supracervical ganglion (SCG) neurons. The beta3-Tg mice had increased heart rate
      and enhanced sensitivity to N-type channel-specific blockers in
      electrocardiography, blood pressure, and echocardiography. In contrast, cardiac
      atria of the beta3-Tg mice revealed normal contractility to isoproterenol.
      Furthermore, their cardiac myocytes showed normal calcium channel currents,
      indicating unchanged calcium influx through VDCCs. Langendorff heart perfusion
      analysis revealed enhanced sensitivity to electric field stimulation in the beta3
      Tg mice, whereas beta3-null and Cav2.2-null showed decreased responsiveness. The
      plasma epinephrine and norepinephrine levels in the beta3-Tg mice were
      significantly increased in the basal state, indicating enhanced sympathetic tone.
      Electrophysiological analysis in SCG neurons of beta3-Tg mice revealed increased
      calcium channel currents, especially N- and L-type currents. These results
      identify a determining role for the beta3 subunit in the N-type channel
      population in SCG and a major role in sympathetic nerve regulation.

PMID- 18628211
TI  - Coexisting asthma and COPD: confused clinicians or poor prognosticator?

PMID- 18628212
TI  - Mechanical catheter intervention in massive pulmonary embolism: proof of concept.

PMID- 18628213
TI  - Filling in the gaps: the role of noninvasive adaptive servoventilation for heart
      failure-related central sleep apnea.

PMID- 18628214
TI  - A new straw in the genesis of Cheyne-Stokes respiration.

PMID- 18628215
TI  - The patient handoff: medicine's Formula One moment.

PMID- 18628217
TI  - Peroxisome proliferator-activated receptors as novel targets in lung disease.
AB  - Inflammatory diseases of the lung such as asthma and COPD represent a major
      worldwide health problem. There are potent antiinflammatory drugs available to
      treat asthma, such as the glucocorticoids, but these produce unwanted side
      effects and exhibit limited efficacy in the treatment of COPD. The identification
      of the peroxisome proliferator-activated receptors (PPARs) PPARgamma, PPARalpha,
      and PPARdelta opened up a new avenue of research as it was discovered that they
      exhibited antiinflammatory and immunomodulatory properties. In animal models of
      allergic and occupational asthma, COPD and pulmonary fibrosis PPARs are involved
      in the inflammatory cascade, and treatment with PPAR agonists reduces
      inflammation and results in beneficial outcomes. The actions of PPARgamma and
      PPARalpha activation are thought to be due to their ability to down-regulate
      proinflammatory gene expression and inflammatory cell functions, and as such
      makes them an attractive target for novel drug intervention. PPARdelta has been
      shown to be involved in wound healing, and its activation may enhance the effects
      of PPARgamma agonists. The only fly in the ointment is the observation of an
      increased incidence of cardiovascular events in diabetic patients treated with
      the PPARgamma agonist rosiglitazone. However, a clinical trial is underway to
      examine the effect of rosiglitazone in asthma patients, and the outcome of this
      trial is awaited with much anticipation. PPARs are novel targets for lung
      disease, and the continued work with PPAR agonists may result in a potential new
      treatment for these chronic inflammatory lung diseases.

PMID- 18628218
TI  - Improving handoff communications in critical care: utilizing simulation-based
      training toward process improvement in managing patient risk.
AB  - BACKGROUND: A patient admitted to the medical step-down unit experienced severe
      hypoglycemia due to an infusion of a higher-than-ordered insulin dose. The event
      could have been prevented if the insulin syringe pump was checked during the
      nursing shift handoff. METHODS: Risk management exploration included direct
      observations of nursing shift handoffs, which highlighted common deficiencies in
      the process. This led to the development and implementation of a handoff protocol
      and the incorporation of handoff training into a simulation-based teamwork and
      communication workshop. A second round of observations took place 6 to 8 weeks
      following training. RESULTS: The intervention demonstrated an increase in the
      incidence of nurses communicating crucial information during handoffs, including
      patient name, events that had occurred during the previous shift, and treatment
      goals for the next shift. However, there was no change in the incidence of
      checking the monitor alarms and the mechanical ventilator. CONCLUSIONS:
      Simulation-based training can be incorporated into the risk management process
      and can contribute to patient safety practice.

PMID- 18628219
TI  - Acute respiratory infections in a recently arrived traveler to your part of the
      world.
AB  - Many acute infectious pulmonary diseases have incubation periods that are long
      enough for travelers to have symptoms after returning home to a health-care
      system that is not familiar with "foreign" infections. Respiratory infections
      have a relatively limited repertoire of clinical manifestations, so that there is
      often nothing characteristic enough about a specific infection to make the
      diagnosis obvious. Thus, the pathway to the diagnosis of infections that are not
      endemic in a region relies heavily on taking a thorough history of both itinerary
      and of specific exposures. One important caveat is that on occasion, the history
      of a recent trip creates an element of "tunnel vision" in the evaluating health
      care provider. It is tempting to relate a person's problem to that recent trip;
      however, when evaluating recent returnees, it is always important to remember
      that the travel may have nothing to do with the patient's presentation. Recent
      travel may add diagnostic considerations to the list of possibilities, but an
      astute clinician must not disregard the possibility that the patient's illness
      has nothing to do with the recent trip.

PMID- 18628220
TI  - Does central venous pressure predict fluid responsiveness? A systematic review of
      the literature and the tale of seven mares.
AB  - BACKGROUND: Central venous pressure (CVP) is used almost universally to guide
      fluid therapy in hospitalized patients. Both historical and recent data suggest
      that this approach may be flawed. OBJECTIVE: A systematic review of the
      literature to determine the following: (1) the relationship between CVP and blood
      volume, (2) the ability of CVP to predict fluid responsiveness, and (3) the
      ability of the change in CVP (DeltaCVP) to predict fluid responsiveness. DATA
      SOURCES: MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation
      review of relevant primary and review articles. STUDY SELECTION: Reported
      clinical trials that evaluated either the relationship between CVP and blood
      volume or reported the associated between CVP/DeltaCVP and the change in stroke
      volume/cardiac index following a fluid challenge. From 213 articles screened, 24
      studies met our inclusion criteria and were included for data extraction. The
      studies included human adult subjects, healthy control subjects, and ICU and
      operating room patients. DATA EXTRACTION: Data were abstracted on study design,
      study size, study setting, patient population, correlation coefficient between
      CVP and blood volume, correlation coefficient (or receive operator characteristic
      [ROC]) between CVP/DeltaCVP and change in stroke index/cardiac index, percentage
      of patients who responded to a fluid challenge, and baseline CVP of the fluid
      responders and nonresponders. Metaanalytic techniques were used to pool data.
      DATA SYNTHESIS: The 24 studies included 803 patients; 5 studies compared CVP with
      measured circulating blood volume, while 19 studies determined the relationship
      between CVP/DeltaCVP and change in cardiac performance following a fluid
      challenge. The pooled correlation coefficient between CVP and measured blood
      volume was 0.16 (95% confidence interval [CI], 0.03 to 0.28). Overall, 56+/-16%
      of the patients included in this review responded to a fluid challenge. The
      pooled correlation coefficient between baseline CVP and change in stroke
      index/cardiac index was 0.18 (95% CI, 0.08 to 0.28). The pooled area under the
      ROC curve was 0.56 (95% CI, 0.51 to 0.61). The pooled correlation between
      DeltaCVP and change in stroke index/cardiac index was 0.11 (95% CI, 0.015 to
      0.21). Baseline CVP was 8.7+/-2.32 mm Hg [mean+/-SD] in the responders as
      compared to 9.7+/-2.2 mm Hg in nonresponders (not significant). CONCLUSIONS: This
      systematic review demonstrated a very poor relationship between CVP and blood
      volume as well as the inability of CVP/DeltaCVP to predict the hemodynamic
      response to a fluid challenge. CVP should not be used to make clinical decisions
      regarding fluid management.

PMID- 18628221
TI  - Extracorporeal membrane oxygenation: current clinical practice, coding, and
      reimbursement.
AB  - Extracorporeal membrane oxygenation (ECMO) is a technique for providing life
      support for patients experiencing both pulmonary and cardiac failure by
      maintaining oxygenation and perfusion until native organ function is restored.
      ECMO is used routinely at many specialized hospitals for infants and less
      commonly for children with respiratory or cardiac failure from a variety of
      causes. Its usage is more controversial in adults, but select medical centers
      have reported favorable findings in patients with ARDS and other causes of severe
      pulmonary failure. ECMO is also rarely used as a rescue therapy in a small subset
      of adult patients with cardiac failure. This article will review the current uses
      and techniques of ECMO in the critical care setting as well as the evidence
      supporting its usage. In addition, current practice management related to coding
      and reimbursement for this intensive therapy will be discussed.

PMID- 18628222
TI  - Beneficial response to macrolide antibiotic in a patient with desquamative
      interstitial pneumonia refractory to corticosteroid therapy.
AB  - Macrolide antibiotics have been shown to have a beneficial effect in a number of
      pulmonary conditions that are characterized by inflammation, including cystic
      fibrosis, asthma, and cryptogenic organizing pneumonia. We report the first case
      of desquamative interstitial pneumonia (DIP) showing a favorable response to
      treatment with clarithromycin. If confirmed, this observation would add DIP to
      the list of pulmonary disorders that are amenable to the beneficial
      antiinflammatory effects of macrolides.

PMID- 18628223
TI  - Case series report of a linezolid-containing regimen for extensively drug
      resistant tuberculosis.
AB  - OBJECTIVE: To determine whether linezolid is safe and well tolerated in the
      treatment of extensively drug-resistant tuberculosis (XDR-TB). MATERIALS AND
      METHODS: The was conducted in a specialized tuberculosis ward for multidrug
      resistant tuberculosis (MDR-TB) on the Chest Service of Bellevue Hospital Center,
      which is a 768-bed public hospital in New York City. Seven patients with
      confirmed MDR-TB or XDR-TB who were still culture positive despite appropriate
      directly observed therapy were treated with a regimen containing linezolid and at
      least one other active agent. RESULTS: The linezolid-containing regimen led to
      sustained negative conversion of sputum cultures and radiographic improvement in
      all patients. Long-term therapy (longest duration of therapy, 28 months) was well
      tolerated in most patients. Neutropenia developed in three patients, but was
      reversible, and peripheral neuropathy developed in two patients. CONCLUSIONS:
      Linezolid remains a promising possible addition to our therapeutic armamentarium
      against XDR-TB. Linezolid is associated with side effects that can be adequately
      managed. Further studies to define the mechanism of action and optimum dose
      should be performed.

PMID- 18628224
TI  - Usual interstitial pneumonia in an adolescent with ABCA3 mutations.
AB  - Many diverse and frequently idiopathic disorders cause interstitial lung disease
      (ILD) in children. Although the histologic patterns of ILD in children and adults
      share similar features, important differences exist in etiology, clinical
      manifestations, and outcome. Usual interstitial pneumonia (UIP) is the most
      frequent histologic pattern in adult ILD; however, the characteristic histologic
      features of UIP have yet to be demonstrated in a child. We report a 15-year-old
      boy with the UIP pattern of pulmonary fibrosis who had mutations in the adenosine
      triphosphate-binding-cassette-A3 gene. Discovery of how genetic mutations of
      proteins involved in surfactant biosynthesis lead to progressive fibrosis will
      have implications for the understanding of the pathogenesis and clinical
      manifestations of ILD in both adults and children.

PMID- 18628225
TI  - A 92-year-old woman with recurrent pleural effusions.

PMID- 18628226
TI  - A 24-year-old man with mediastinal mass, dyspnea, and a pleural effusion.

PMID- 18628227
TI  - Keep attendees awake: writing effective presentations for international
      conferences.

PMID- 18628228
TI  - Diffuse ground-glass opacities in a patient with Hodgkin lymphoma and progressive
      respiratory failure.

PMID- 18628231
TI  - Blood banks under siege.

PMID- 18628232
TI  - Using intraoperative goal-directed hemodynamic management shows dobutamine to be
      effective in maintaining central venous oxygen saturation.

PMID- 18628233
TI  - Both spontaneous pneumothorax and spontaneous pneumomediastinum may constitute a
      complication in underweight patients.

PMID- 18628234
TI  - Variability in the prevalence of acute bronchoresponsiveness in different
      populations of patients with lymphangioleiomyomatosis.

PMID- 18628235
TI  - Positive airway pressure therapy and daytime hypercapnia in patients with sleep
      disordered breathing.

PMID- 18628236
TI  - Muscle function in smokers: clearing up the smoke.

PMID- 18628237
TI  - Characterization of a lymphocyte subset displaying a unique regulatory activity
      in human decidua.
AB  - One of the most intriguing mechanisms of early pregnancy is the maternal immune
      tolerance toward her semi-allogeneic fetus, specifically in face of the
      accumulation of lymphocytes to high numbers at implantation sites. Here, we
      propose that a regulatory decidual lymphocyte (dL) population prevent the
      activation of reactive T cells and by that may maintain immune tolerance in the
      decidua. dLs were isolated from first trimester decidua and were then co-cultured
      with PBMC that were stimulated with anti-CD3 mAbs. Cytokine secretion to the
      media as well as the proliferative response were tested. The data demonstrate
      that dLs inhibit the production of IFN-gamma, tumor necrosis factor-alpha (TNF
      alpha) and IL-5 but not CD25 expression, IL-2 production or proliferation in the
      responder PBMC. Suppression is mediated by a cell contact-dependent mechanism,
      was not restricted by the MHC and was not reversed by the addition of exogenous
      IL-2 although the inhibitory sub-population was identified as CD3+CD4+CD25+Foxp3+
      natural regulatory T cells (Treg). Interestingly, suppression can also be
      overcome by the addition the endotoxin LPS, suggesting a mechanism for preterm
      labor triggered by chorioamnionitis. While these characteristics are in contrast
      to known peripheral CD4+CD25+ Treg activity, we identified these cells as the
      cellular subset responsible for the regulatory activity, suggesting that in
      decidua a functionally unique regulatory lymphocyte subset exist. These findings
      suggest the existence of a dynamic regulatory system in human decidua that is
      highly responsive to environmental factors.

PMID- 18628238
TI  - Recombinant surfactant protein-D selectively increases apoptosis in eosinophils
      of allergic asthmatics and enhances uptake of apoptotic eosinophils by
      macrophages.
AB  - Pulmonary surfactant protein-D (SP-D) is a multifunctional, pattern recognition
      molecule involved in resistance to allergen challenge and pulmonary inflammation.
      In view of therapeutic effects of exogenous SP-D or recombinant fragment of human
      surfactant protein-D (rhSP-D) (composed of eight Gly-X-Y collagen repeat
      sequences, homotrimeric neck and lectin domains) in murine models of lung allergy
      and hypereosinophilic SP-D gene-deficient mice, we investigated the possibility
      of a direct interaction of purified rhSP-D with human eosinophils derived from
      allergic patients and healthy donors. rhSP-D showed a sugar- and calcium
      dependent binding to human eosinophils, suggesting involvement of its
      carbohydrate recognition domain. While eosinophils from allergic patients showed
      a significant increase in apoptosis, oxidative burst and CD69 expression in
      presence of rhSP-D, eosinophils from healthy donors showed no significant change.
      However, these eosinophils from healthy donors when primed with IL-5 exhibited
      increase in apoptosis on incubation with rhSP-D. Apoptosis mediated by rhSP-D in
      primed eosinophils was not affected by the antioxidant, N-acetyl-L-cysteine.
      There was a manifold increase in binding of rhSP-D to apoptotic eosinophils than
      the normal eosinophils and rhSP-D induced a significant increase in uptake of
      apoptotic eosinophils by J774A.1 macrophage cells. The study suggests that rhSP-D
      mediated preferential increase of apoptosis of primed eosinophils while not
      affecting the normal eosinophils and increased phagocytosis of apoptotic
      eosinophils may be important mechanisms of rhSP-D and plausibly SP-D-mediated
      resolution of allergic eosinophilic inflammation in vivo.

PMID- 18628239
TI  - Recombination of protein fragments: a promising approach toward engineering
      proteins with novel nanomechanical properties.
AB  - Combining single molecule atomic force microscopy (AFM) and protein engineering
      techniques, here we demonstrate that we can use recombination-based techniques to
      engineer novel elastomeric proteins by recombining protein fragments from
      structurally homologous parent proteins. Using I27 and I32 domains from the
      muscle protein titin as parent template proteins, we systematically shuffled the
      secondary structural elements of the two parent proteins and engineered 13 hybrid
      daughter proteins. Although I27 and I32 are highly homologous, and homology
      modeling predicted that the hybrid daughter proteins fold into structures that
      are similar to that of parent protein, we found that only eight of the 13
      daughter proteins showed beta-sheet dominated structures that are similar to
      parent proteins, and the other five recombined proteins showed signatures of the
      formation of significant alpha-helical or random coil-like structure. Single
      molecule AFM revealed that six recombined daughter proteins are mechanically
      stable and exhibit mechanical properties that are different from the parent
      proteins. In contrast, another four of the hybrid proteins were found to be
      mechanically labile and unfold at forces that are lower than the approximately 20
      pN, as we could not detect any unfolding force peaks. The last three hybrid
      proteins showed interesting duality in their mechanical unfolding behaviors.
      These results demonstrate the great potential of using recombination-based
      approaches to engineer novel elastomeric protein domains of diverse mechanical
      properties. Moreover, our results also revealed the challenges and complexity of
      developing a recombination-based approach into a laboratory-based directed
      evolution approach to engineer novel elastomeric proteins.

PMID- 18628240
TI  - Toward the semisynthesis of multidomain transmembrane receptors: modification of
      Eph tyrosine kinases.
AB  - Expressed protein ligation (EPL) is a protein engineering approach that allows
      the modification or assembly of a target protein from multiple recombinant and
      synthetic polypeptides. EPL has been previously used to modify intracellular
      proteins and small integral membrane proteins for structural and functional
      studies. Here we describe the semisynthetic site-specific modification of the
      complete, multidomain extracellular regions of both A and B classes of Eph
      receptor tyrosine kinases. We show that the ectodomains of these receptors can be
      ligated to different peptides under carefully established experimental
      conditions, while their biological activity is retained. This work extends the
      boundaries of the EPL technique for semisynthesis of multidomain, extracellular,
      disulfide-bonded, and glycosylated proteins and highlights its potential
      application for reconstituting entire single-pass transmembrane proteins.

PMID- 18628241
TI  - Helix XI contributes to the entrance of the serotonin transporter permeation
      pathway.
AB  - The sodium-dependent transporters for dopamine, norepinephrine, and serotonin
      that regulate neurotransmission, also translocate the neurotoxin 1-methyl-4
      phenylpyridinium (MPP(+)). Previous studies implicated residues in transmembrane
      helix (TMH) XI of DAT as important sites for MPP(+) transport. We examined the
      importance of TMH XI residues F551 and F556 for MPP(+) translocation by human
      SERT. Mutations at hSERT F556, but not F551, reduced both 5-HT and MPP(+)
      transport compared to wild type. However, F556S/hSERT showed a reduction in
      surface expression explaining the decrease of transport activity for 5-HT, but
      did not account for the decrease in MPP(+) transport observed. Cysteine mutants
      at those positions confirmed the accessibility of hSERT/F556 to different
      methanethiosulfonate (MTS) reagents, suggesting its presence in a hydrophilic
      environment of the protein. In the presence of MTSET, current induced by 5-HT and
      MPP(+) was inhibited at the F556C mutant. In agreement with our homology model of
      SERT, based on the leucine transporter (LeuT(Aa)) from Aquifex aeolicus
      structure, these results are consistent with the hypothesis that a portion of TMH
      XI lines the entrance into the substrate permeation pathway.

PMID- 18628242
TI  - Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the
      European prospective investigation into cancer and nutrition (EPIC-EURGAST).
AB  - BACKGROUND: The relative contribution to gastric cancer (GC) risk of variants in
      genes that determine the inflammatory response remains mostly unknown and results
      from genotyping studies are inconsistent. PATIENTS AND METHODS: A nested case
      control study within the prospective European Prospective Investigation into
      Cancer and Nutrition cohort was carried out, including 248 gastric
      adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine
      genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B,
      lymphotoxin alpha and tumor necrosis factor (TNF)] were analyzed. Antibodies
      against Helicobacter pylori (Hp) and CagA were measured. RESULTS: IL1RN 2R/2R
      genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and
      allele IL1RN Ex5-35C were associated with an increased risk of Hp(+) non-cardia
      GC. IL8 -251AA genotype was associated with a decreased risk of Hp(+) non-cardia
      GC (OR 0.51; 95% CI 0.32-0.81), mainly of the intestinal type. These associations
      were not modified by CagA status. Carriers of IL1B -580C and TNF -487A alleles
      did not associate with an increased risk. A moderately increased risk of Hp(+)
      non-cardia GC for IL4R -29429T variant was observed (OR 1.74; 95% CI 1.15-2.63).
      CONCLUSION: This prospective study confirms the association of IL1RN
      polymorphisms with the risk of non-cardia GC and indicates that IL8 -251T>A may
      modify the risk for GC.

PMID- 18628243
TI  - Processes of care desired by elderly patients with multimorbidities.
AB  - BACKGROUND: Most recommended care for chronic diseases is based on the research
      of single conditions. There is limited information on 'best' processes of care
      for persons with multiple morbidities. Our objective was to explore processes of
      care desired by elderly patients who have multimorbidities that may present
      competing demands for patients and providers. METHODS: Qualitative investigation
      using one-on-one interviews of 26 community-dwelling HMO members aged 65-84 (50%
      male) who had, at a minimum, the combined conditions of diabetes, depression and
      osteoarthritis. Participants were chosen from a stratified random sample to have
      a range of 4-16 chronic medical conditions. RESULTS: Participants' desired
      processes of care included: the need for convenient access to providers
      (telephone, internet or in person), clear communication of individualized care
      plans, support from a single coordinator of care who could help prioritize their
      competing demands and continuity of relationships. They also desired providers
      who would listen to and acknowledge their needs, appreciate that these' needs
      were unique and fluctuating and have a caring attitude. CONCLUSIONS: These
      respondents describe an ideal process of care that is patient centered and
      individualized and that supports their unique constellations of problems,
      shifting priorities and multidimensional decision making. Individual and ongoing
      care coordination managed by a primary contact person may meet some of these
      needs. Achieving these goals will require developing efficient methods of
      assessing patient care needs and flexible care management support systems that
      can respond to patients' needs for different levels of support at different
      times.

PMID- 18628244
TI  - Inducing catastrophe in malignant growth.
AB  - Mathematical catastrophe theory is used to describe cancer growth during any time
      dependent program a(t) of therapeutic activity. The program may be actively
      imposed, e.g. as chemotherapy, or occur passively as an immune response. With
      constant therapy a(t), the theory predicts that cancer mass p(t) grows in time t
      as a cosine-modulated power law, with power = 1.618..., the Fibonacci constant.
      The cosine modulation predicts the familiar relapses and remissions of cancer
      growth. These fairly well agree with clinical data on breast cancer recurrences
      following mastectomy. Two such studies of 3183 Italian women consistently show an
      immune system's average activity level of about a = 2.8596 for the women.
      Fortunately, an optimum time-varying therapy program a(t) is found that effects a
      gradual approach to full remission over time, i.e. to a chronic disease. Both
      activity a(t) and cancer mass p(t) monotonically decrease with time, the activity
      a(t) as 1/(ln t) and mass remission as t--94{-0.382}. These predicted growth
      effects have a biological basis in the known presence of multiple alleles during
      cancer growth.

PMID- 18628245
TI  - An overset grid method for the study of reflex tearing.
AB  - We present an overset grid method to simulate the evolution of human tear film
      thickness subject to reflex tearing. The free-surface evolution is governed by a
      single fourth-order non-linear equation derived from lubrication theory with
      specified film thickness and volume flux at each end. The model arises from
      considering the limiting case where the surfactant is strongly affecting the
      surface tension. In numerical simulations, the overset grid is composed of fine
      boundary grids near the upper and lower eyelids to capture localized capillary
      thinning referred to as 'black lines' and a Cartesian grid covers the remaining
      domain. Numerical studies are performed on a non-linear test problem to confirm
      the accuracy and convergence of the scheme. The computations on the tear film
      model show qualitative agreement with in vivo tear film thickness measurements.
      Furthermore, the role of the black lines in the presence of tear supply from the
      lid margins, reflex tearing, was found to be more subtle than a barrier to tear
      fluid flow between the anterior of the eye and the meniscus at the lid margin.
      During reflex tearing, tears may flow through the region normally containing the
      black line and drift down over the cornea under the influence of gravity.

PMID- 18628246
TI  - HIV post-exposure prophylaxis among police and corrections officers.
AB  - BACKGROUND: Police and correctional officers face the occupational hazard of
      blood and body fluid exposures, which carry the risk of infection with HIV. AIMS:
      To estimate the incidence rate (IR) of emergency department (ED) visits for blood
      or body fluid exposures sustained by police and corrections officers in an entire
      state and to quantify the utilization of HIV post-exposure prophylaxis (PEP) in
      response to these exposures. METHODS: A retrospective study of police and
      corrections officers presenting to EDs in Rhode Island between 1995 and 2001. The
      investigators estimated IRs of ED visits for these exposures with 95% confidence
      intervals and determined factors associated with HIV PEP using bivariate
      Pearson's chi2 analyses. RESULTS: The average annual incidence of ED visits for
      blood or body fluid exposures over the study period was IR 4.41 (2.31-6.51)
      exposures per 1000 police and corrections personnel. Only 15% of officers
      sustained percutaneous injuries or blood-to-mucous membrane exposures. Sixteen
      officers were offered HIV PEP and 10 accepted it. Offering of HIV PEP was 3.3
      fold greater for officers sustaining percutaneous and blood-to-mucous membrane
      exposures instead of other body fluid exposures. CONCLUSION: The incidence of ED
      visits for blood or body fluid exposures by police and corrections officers was
      low and most exposures did not have the potential for HIV transmission. HIV PEP
      was infrequently used for these exposures.

PMID- 18628247
TI  - Occupational exposures among domestic and industrial professional cleaners.
AB  - BACKGROUND: Despite being a large part of the workforce, cleaners remain a
      relatively understudied occupational group in the USA. AIMS: The aims of this
      focus group study were to identify and characterize occupational exposures,
      symptoms and job tasks among domestic and industrial professional cleaners.
      METHODS: Twelve focus group sessions were conducted in Lubbock, TX, and Houston,
      TX. Participants were asked about their job tasks, type of products they use to
      clean, bodily symptoms, job training and work environment. RESULTS: Out of 99
      attendees, 79 domestic and industrial cleaners participated actively in the focus
      group sessions. Three general themes emerged regarding cleaning professionals'
      work experiences: (i) job training, (ii) chemical exposure and use and (iii)
      competence. Domestic cleaners demonstrated significant skills deficit across each
      of these three themes as compared to industrial cleaners. Domestic cleaners
      reported more frequent exposure to respiratory irritants and sensitizers and also
      reported adverse respiratory symptoms as compared to industrial cleaners.
      CONCLUSIONS: The results from this qualitative study are consistent with earlier
      findings from quantitative studies placing domestic cleaners at risk of exposure
      to chemicals that are respiratory irritants and/or sensitizers.

PMID- 18628248
TI  - Quercetin inhibition of tumor invasion via suppressing PKC delta/ERK/AP-1
      dependent matrix metalloproteinase-9 activation in breast carcinoma cells.
AB  - Quercetin (QUE; 3,5,7,3',4'-tetrahydroxyflavone) has been shown to possess
      several beneficial biological activities including antitumor, anti-inflammation
      and antioxidant properties; however, the effects of QUE in preventing invasion by
      breast carcinoma cells are still undefined. Increases in the protein, messenger
      RNA and enzyme activity levels of matrix metalloproteinase (MMP)-9 were observed
      in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells, and these were
      blocked by QUE, but not by quercitrin or rutin. A translocation of protein kinase
      C (PKC)delta from the cytosol to the membrane followed by activation of
      extracellular signal-regulated kinase (ERK) and c-Jun/activator protein-1 (AP-1)
      by TPA was demonstrated, and TPA-induced MMP-9 activation and migration were
      inhibited by the pan PKC inhibitor, GF109203X, the specific PKCdelta inhibitor,
      rottlerin, an ERK inhibitor (PD98059) and an AP-1 inhibitor (curcumin).
      Application of QUE significantly suppressed TPA-induced activation of the
      PKCdelta/ERK/AP-1-signaling cascade. To elucidate the importance of hydroxyl (OH)
      substitutions to QUE's inhibition of tumor migration, several structurally
      related flavones of QUE including 3',4'-diOH, 3',4'-diOCH(3), 3,5,7-triOH,
      3,4',4'-triOH, 3,3',4'-triOCH(3), luteolin and fisetin were used. Results
      suggested that OH groups at both C3' and C4' play central roles in QUE's
      inhibition of TPA-induced MMP-9 activation and migration, and an additional OH at
      C3, C5 or C7 may increase the inhibitory potency of the 3',4'-diOH flavone
      against TPA-induced MMP-9 activity and migration. The antitumor invasion and
      migration effects of breast carcinoma cells induced by QUE with the structure
      activity relationship analysis were identified.

PMID- 18628249
TI  - Association of vitamin D receptor gene variants, adiposity and colon cancer.
AB  - Vitamin D receptor (VDR) gene variants have been variably associated with risk of
      colon cancer in epidemiologic studies. We sought to further clarify the
      relationship between colon cancer and three single-nucleotide polymorphisms
      (SNPs) in the VDR gene (Cdx-2, FokI and TaqI) in a population-based case-control
      study of 250 incident cases and 246 controls. Colon cancer cases were more
      frequently homozygous for the Cdx-2 A allele (9.2 versus 4.1%, P = 0.06). Cdx-2
      AA homozygotes were at increased risk with an unadjusted odds ratio (OR) of 2.47
      [95% confidence interval (CI): 1.13-5.37, P = 0.022]; adjustment for age, sex,
      body mass index (BMI), non-steroidal anti-inflammatory use and family history of
      colorectal cancer yielded an OR of 2.27 (CI: 0.95-5.41, P = 0.065). Carriers of
      the FokI TT genotype were also at increased risk with an adjusted OR of 1.87 (CI:
      1.03-3.38, P = 0.038). Haplotype analyses showed significant increased colon
      cancer risk for carriers of the Cdx-2-FokI A-T haplotype and the FokI-TaqI T-G
      haplotype. The three-SNP Cdx-2-FokI-TaqI (A-T-G) haplotype showed a similar
      association with an adjusted OR of 3.63 (CI: 1.01-13.07). A strong positive
      association was observed for the Cdx-2 variant among individuals with low BMI or
      low waist circumference. Our results suggest that genetic variation at the VDR
      locus, in particular Cdx-2 and FokI SNPs, may influence colon cancer risk and
      these associations may be modified by adiposity.

PMID- 18628251
TI  - Influence of interleukin-8 and interleukin-10 on sporadic colon cancer
      development and progression.
AB  - Cytokines produced in the tumour microenvironment have an important role in
      cancer pathogenesis. Altered cytokine expression may result in increased
      susceptibility to and/or poor prognosis in certain cancers. Therefore, the aim of
      this study was to investigate the influence of interleukin (IL)-8 and IL-10 on
      sporadic colon cancer development and progression. In our study, a statistically
      significant increase in IL-8 messenger RNA (mRNA) expression and decrease in IL
      10 mRNA expression in tumour tissue compared with normal mucous tissue was
      observed (P = 0.003; P = 1.3 x 10(-9)). No association was found between IL-8 
      251 A/T genotypes and IL-8 mRNA expression in tumour and corresponding normal
      mucous tissue, as well as susceptibility to sporadic colon cancer. Positive
      immunohistochemical IL-8 staining was more frequent in moderately and poorly
      differentiated tumours compared with well-differentiated tumours (P = 0.024).
      Finally, IL-8 significantly stimulated invasion of HT-29 cells in vitro (P =
      0.000172). Significant association of IL-10 -1082 A/G, -819 T/C and -592 A/C
      genotypes and IL-10 mRNA expression in tumour tissue was observed (P = 0.022; P =
      0.013; P = 0.02). Significant association of -819 T/C and -592 A/C genotypes and
      IL-10 mRNA expression in corresponding normal mucous tissue was observed (P =
      0.01; P = 0.04) as well. IL-10 single-nucleotide polymorphism (SNP) promoter
      genotypes associated with low IL-10 mRNA expression (-819 TT; -592 AA) were also
      associated with increased risk of sporadic colon cancer compared with high
      expression genotypes [odds ratio, 5.53; 95% confidence interval (CI), 1.53-20.1;
      odds ratio, 4.07; 95% CI, 1.28-12.96]. Positive IL-10 immunohistochemical
      reaction was more frequent in well-differentiated and moderately differentiated
      tumours compared with poorly differentiated tumours (P = 0.036). In Dukes' C
      tumours, positive IL-10 immunohistochemical reaction was less frequent compared
      with Dukes' A and B tumours (P = 0.023). Taken together, our results point to
      possible tumour promoting role of IL-8 and potential protective role of IL-10 in
      sporadic colon cancer.

PMID- 18628252
TI  - Subacute oral exposure to dibromoacetic acid induced immunotoxicity and apoptosis
      in the spleen and thymus of the mice.
AB  - Dibromoacetic acid (DBA) is a haloacetic acid that is present in drinking water
      as a by-product of chlorinated disinfection. To evaluate its potential adverse
      health effects, the immunotoxicological effects of DBA on the thymus and spleen
      of BALB/c mice were investigated. Groups of mice (10 mice per group) were
      administered DBA at doses of 0, 5, 20, and 50 mg/kg body weight daily for 28 days
      via oral gavage. The mice orally administered DBA exhibited obvious
      immunotoxicity, as indicated by changes in the thymus and spleen. DBA induced a
      dose-dependent decrease and increase in thymus weight and spleen weight,
      respectively. The histological changes were cortical atrophy of the thymus, white
      pulp shrinkage of the spleen, and apoptosis of many splenic and thymic
      lymphocytes; these observations were confirmed by morphometric analysis of the
      electron microscope scans. Lymphocytes proliferation analysis indicated that the
      proliferative function of the splenic and thymic lymphocytes was altered after
      DBA exposure. Cell death via apoptosis was analyzed with an annexin-V/propidium
      iodide assay by flow cytometry, and we observed that the percentage of apoptosis
      increased in a dose-dependent manner after DBA treatment. In addition, DBA
      treatment altered the expression of a few apoptosis-related genes such as Fas,
      TRAF2, bcl-2, and bax in a dose-dependent manner. Western blot analysis revealed
      increased expression of the Fas and FasL proteins. In conclusion, DBA induces
      obvious immunotoxicity in the thymus and spleen, and immune-cell apoptosis
      mediated by the Fas/FasL pathway may be the potential mechanism underlying this
      immunotoxicity.

PMID- 18628250
TI  - Allyl mercaptan, a garlic-derived organosulfur compound, inhibits histone
      deacetylase and enhances Sp3 binding on the P21WAF1 promoter.
AB  - Histone deacetylase (HDAC) inhibitors have the potential to derepress
      epigenetically silenced genes in cancer cells, leading to cell cycle arrest and
      apoptosis. In the present study, we screened several garlic-derived small
      organosulfur compounds for their ability to inhibit HDAC activity in vitro. Among
      the organosulfur compounds examined, allyl mercaptan (AM) was the most potent
      HDAC inhibitor. Molecular modeling, structure activity and enzyme kinetics
      studies with purified human HDAC8 provided evidence for a competitive mechanism
      (K(i) = 24 microM AM). In AM-treated human colon cancer cells, HDAC inhibition
      was accompanied by a rapid and sustained accumulation of acetylated histones in
      total cellular chromatin. Chromatin immunoprecipitation assays confirmed the
      presence of hyperacetylated histone H3 on the P21WAF1 gene promoter within 4 h of
      AM exposure, and there was increased binding of the transcription factor Sp3. At
      a later time, 24 h after AM treatment, there was enhanced binding of p53 in the
      distal enhancer region of the P21WAF1 gene promoter. These findings suggest a
      primary role for Sp3 in driving P21 gene expression after HDAC inhibition by AM,
      followed by the subsequent recruitment of p53. Induction of p21Waf1 protein
      expression was detected at time points between 3 and 72 h after AM treatment and
      coincided with growth arrest in G(1) of the cell cycle. The results are discussed
      in the context of other anticarcinogenic mechanisms ascribed to garlic
      organosulfur compounds and the metabolic conversion of such compounds to
      potential HDAC inhibitors in situ.

PMID- 18628253
TI  - Sensitivity analysis of biologically motivated model for formaldehyde-induced
      respiratory cancer in humans.
AB  - Conolly et al. (2003, 2004) developed biologically motivated models of
      formaldehyde carcinogenicity in F344 rats and humans based on a two-stage clonal
      expansion model of cancer. Based on the human model, Conolly et al. (2004)
      claimed that cancer risks associated with inhaled formaldehyde are deminimis at
      relevant human exposure levels. However, they did not conduct a sensitivity
      analysis to evaluate the robustness of this conclusion. Here, we present a
      limited sensitivity analysis of the formaldehyde human model. We show that when
      the control animals from the National Toxicology Program (NTP) studies are
      replaced with control animals only from NTP inhalation studies, estimates of
      human risk are increased by 50-fold. When only concurrent control rats are used,
      the model does not provide any upper bound (UB) to human risk. No data went into
      the model on the effect of formaldehyde on the division rates and death rates of
      initiated cells. We show that slight numerical perturbations to the Conolly et
      al. assumptions regarding these rates can be made that are equally consistent
      with the underlying data used to construct the model, but produce estimates of
      human risk ranging anywhere from negative up to 10,000 times higher than those
      deemed by Conolly et al. to be 'conservative'. Thus, we conclude that estimates
      of human risk by Conolly et al. (2004) are extremely sensitive to modeling
      assumptions. This calls into question the basis for the Conolly et al. claim of
      de minimis human risk and suggests caution in using the model to derive human
      exposure standards for formaldehyde.

PMID- 18628254
TI  - E2F2 expression induces proliferation of terminally differentiated cardiomyocytes
      in vivo.
AB  - AIMS: In previous experiments we have demonstrated that expression of the
      transcription factors E2F2 and E2F4 is sufficient to induce proliferation of
      isolated primary cardiomyocytes from newborn rats and mice. We now wanted to
      analyse whether E2F2 or E2F4 are also able to promote cell cycle progression of
      adult cardiomyocytes in vivo, which unlike cardiomyocytes from newborn rodents
      lack the ability to undergo cell proliferation. METHODS AND RESULTS: E2F2 or E2F4
      was expressed in hearts of mice at different developmental stages using
      adenoviral vectors. Effects regarding proliferation, hypertrophy, and apoptosis
      were analysed on histological sections, and quantitative assessment of cell cycle
      regulatory genes was performed by real-time PCR (polymerase chain reaction) and
      western blot. We found that both E2F2 and E2F4 can stimulate hypertrophic cell
      growth of cardiomyocytes. However, only directed expression of E2F2 but not of
      E2F4 was sufficient to induce proliferation of cardiomyocytes. Expression of E2F2
      in vivo did not increase the percentage of apoptotic cardiomyocytes but down
      regulated the expression of the pro-apoptotic genes caspase-6 and apaf-1. Further
      analysis of the cell cycle regulatory machinery revealed that expression of E2F2
      caused a strong induction of cyclin A and E while the expression of cyclin
      dependent kinase inhibitors (CKIs) such as p21 was not affected. CONCLUSION: We
      conclude that a limited induction of cardiomyocyte cell proliferation can be
      achieved by E2F2-mediated stimulation of cyclin A and E expression without a
      reduction of CKIs.

PMID- 18628255
TI  - P55 tumour necrosis factor receptor in bone marrow-derived cells promotes
      atherosclerosis development in low-density lipoprotein receptor knock-out mice.
AB  - AIMS: Tumour necrosis factor (TNF) is a pivotal pro-inflammatory cytokine with a
      clear pathogenic role in many chronic inflammatory diseases, and p55 TNF receptor
      (TNFR) mediates the majority of TNF responses. The aim of the current study was
      to investigate the role of p55 TNFR expression in bone marrow-derived cells, in
      atherosclerotic lesion development. METHODS AND RESULTS: Irradiated low-density
      lipoprotein receptor knock-out mice were reconstituted with either p55 TNFR knock
      out or control haematopoietic stem cells to generate chimeras deficient or wild
      type for p55 TNFR specifically in bone marrow-derived cells, including
      macrophages. Upon high fat feeding, p55 TNFR knock-out transplanted mice
      developed smaller atherosclerotic lesions. These lesions were characterized by
      the presence of smaller foam cells and a reduced macrophage foam cell area. They
      did not differ in other compositional characteristics as determined by
      quantification of inflammatory T-cell and neutrophil influx, apoptotic and
      necrotic cell death, and collagen content. In vitro studies confirmed a
      significant defect in modified lipoprotein endocytosis by p55 TNFR knock-out
      macrophages due to reduced scavenger receptor class A expression. Interestingly,
      plasma cytokine/chemokine profile analysis indicated that monocyte
      chemoattractant protein-1 (MCP-1) levels, a major chemokine involved in
      atherogenesis, were consistently and significantly lower in p55 TNFR knock-out
      transplanted mice compared with controls, before and after high fat feeding.
      CONCLUSION: p55 TNFR expression in bone marrow-derived cells contributes to the
      development of atherosclerosis by enhancing lesional foam cell formation and by
      promoting the expression of pro-atherosclerotic chemokines such as MCP-1.

PMID- 18628256
TI  - Role of transoesophageal echocardiography in evaluating the effect of catheter
      ablation of atrial fibrillation on anatomy and function of the pulmonary veins.
AB  - AIMS: Radiofrequency ablation (ABL) of pulmonary veins (PVs) is an effective
      treatment of atrial fibrillation (AF). The aim of this study was to evaluate the
      possible morphological and functional consequences of this procedure on PV during
      a 12-month follow-up. METHODS AND RESULTS: Ninety-six patients underwent
      transoesophageal echocardiography (TEE) before ABL, and 48 h, 3, and 12 months
      later. The peak velocity, mean velocity, mean/peak flow velocity, and diameter of
      each vein were measured at every follow-up examination. All patients also
      underwent multidimensional computer tomography (MCT) 3 months after ABL. At the
      first control, a 5% reduction in PV diameters and an increase in the peak
      velocity, mean velocity, and mean/peak velocity (34.3, 42.2, and 6.9,
      respectively: P < 0.000) of their Doppler flow were observed. Later follow-up
      examinations revealed no further significant increase in PV narrowing or flow
      velocities. MCT showed PV stenoses (>50%) in four PVs, while TEE showed a >100%
      increase over basal values in flow velocities and a plateau configuration of the
      pulsed-wave Doppler spectrum. CONCLUSION: ABL of AF reduces the diameter and
      increases the flow velocities of PV. However, critical stenosis is rare and can
      be diagnosed by TEE through a marked change in the velocities and in the
      configuration of the Doppler flow.

PMID- 18628257
TI  - Is atrial fibrillation with very short cycle length suitable for ablation? A case
      report.
AB  - We present a case of a 36-year-old woman with highly symptomatic persistent
      atrial fibrillation (AF) refractory to sotalol, flecainide, and external direct
      current (DC) cardioversion. The patient underwent biatrial mapping and ablation
      procedure for AF. Both atria were characterized by refractory properties which
      were much shorter than reported previously. Global fibrillatory activity was
      present with a median cycle length of 120 ms (range: 62-143). Extensive map
      guided ablation sets had to be delivered to both left and right sides before
      effective DC cardioversion enabled sinus rhythm (SR) restoration. The patient
      remained in SR at 9 months of follow-up.

PMID- 18628258
TI  - Biatrial anatomical reverse remodelling after radiofrequency catheter ablation
      for atrial fibrillation: evidence from real-time three-dimensional
      echocardiography.
AB  - AIMS: Reports using two-dimensional echocardiography have indicated that
      radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) results in a
      reduction in the left atrial (LA) size. Furthermore, the effect of pulmonary vein
      isolation (PVI) on right atrial (RA) anatomical remodelling has not been studied.
      Three-dimensional echocardiography (3DE) allows us to more precisely quantify
      atrial volume. Our aim was to assess the effect of PVI on biatrial anatomical
      remodelling using real-time 3DE. METHODS AND RESULTS: We prospectively studied 91
      patients (age 59 +/- 8 years, 79 males) referred for RFCA of paroxysmal (n = 79)
      or chronic (n = 19) AF. Left atrial and RA volumes were measured using real-time
      3DE at baseline and after 6 months of follow-up. Data on AF recurrences were also
      collected. Left atrial volume was significantly reduced at follow-up when
      compared with baseline (51 +/- 16 vs. 60 +/- 21 mL, P < 0.001). The same occurred
      with RA volume (43 +/- 17 vs. 50 +/- 20 mL, P = 0.001). The reduction in the LA
      volume was more marked in patients with chronic than in those with paroxysmal AF
      (17 +/- 16 vs. 6 +/- 17 mL, P = 0.017). Patients with AF recurrence (23%) showed
      similar atrial volume reduction compared with those who were seemingly cured.
      CONCLUSION: Three-dimensional echocardiography shows evidence of biatrial
      anatomical reverse remodelling after RFCA for AF. A reduction in the atrial
      volume occurs despite recurrence of AF.

PMID- 18628259
TI  - A feasibility study of a brief coping intervention (PRCI) for the waiting period
      before a pregnancy test during fertility treatment.
AB  - BACKGROUND: Waiting for a pregnancy test during fertility treatment can be
      particularly stressful because distress and intrusive cognitions about the nature
      and implications of the result can reduce quality of life. The aim of this
      feasibility study was to establish whether a novel brief coping intervention
      (positive reappraisal coping intervention, PRCI) card that encouraged women
      waiting for an IVF pregnancy test to redefine the waiting period more positively
      would be acceptable and practical in this context. METHODS: Women (n = 55) were
      randomly assigned on the day of embryo transfer. Women read either 10 statements
      in a PRCI (n = 28) or 10 statements in a positive self-affirmative (positive
      mood) intervention (PMI; n = 27) twice daily for 14 days between embryo transfer
      (T1) and the pregnancy test (T2). At T2, we evaluated the practicality,
      acceptability, perceived benefits and endorsements of these cards. RESULTS:
      Compared with the PMI, the PRCI was rated as more helpful and suitable for the
      situation, helping women to feel more positive and better helping to sustain
      efforts to cope. There were no differences relating to the practicality of the
      intervention method. CONCLUSIONS: PRCI was feasible in the IVF context and was
      perceived as an acceptable intervention to help minimize the strain of waiting
      for pregnancy test results during fertility treatment. Future research needs to
      evaluate the full benefits of PRCI against routine care during the waiting
      period.

PMID- 18628260
TI  - Neonatal outcome of 937 children born after transfer of cryopreserved embryos
      obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF
      cycles.
AB  - BACKGROUND: To evaluate the safety of cryopreservation in combination with IVF
      and ICSI, prenatal diagnosis and neonatal outcome were investigated in children
      conceived from frozen-thawed ICSI embryos (cryo ICSI) and frozen-thawed IVF
      embryos (cryo IVF). Data were also compared with earlier published results from
      fresh ICSI and IVF embryos. METHODS: Questionnaire data and results of physical
      examination at 2 months of 547 cryo ICSI children and 390 cryo IVF children were
      compared, and these were also compared with those of infants born after transfer
      of fresh embryos. RESULTS: Birth characteristics were comparable for cryo ICSI
      and cryo IVF infants. Cryo singletons showed a trend towards higher mean
      birthweight compared with fresh singletons, in ICSI and IVF, reaching
      significance when all cryo (ICSI plus IVF) singletons were considered. Low
      birthweight rate according to multiplicity was comparable between the fresh and
      the cryo groups, in ICSI and IVF. Non-statistically significantly increased rates
      of de novo chromosomal anomalies (3.2%) were found in cryo ICSI fetuses/children
      compared with the fresh ICSI group (1.7%) (OR 1.96; 95% CI 0.92-4.14). Major
      malformations were more frequently observed in cryo ICSI live borns (6.4%) than
      in cryo IVF live borns (3.1%) (OR 2.15; 95% CI 1.10-4.20) and fresh ICSI live
      borns (3.4%) (OR 1.96; 95% CI 1.31-2.91). CONCLUSIONS: In cryo ICSI compared with
      cryo IVF, prenatal and neonatal outcome results were comparable, except for a
      higher major malformation rate in the cryo ICSI group. In the total cryo group
      compared with the total fresh group, we found a higher mean birthweight in
      singletons and a higher major malformation rate in live borns.

PMID- 18628261
TI  - Clinical outcomes in randomized trials of off- vs. on-pump coronary artery bypass
      surgery: systematic review with meta-analyses and trial sequential analyses.
AB  - AIMS: To assess the clinical outcomes of off- vs. on-pump coronary artery bypass
      surgery in randomized trials. METHODS AND RESULTS: We searched electronic
      databases and bibliographies until June 2007. Trials were assessed for risk of
      bias. Outcome measures were all-cause mortality, myocardial infarction, stroke,
      atrial fibrillation, and renewed coronary revascularization at maximum follow-up.
      We applied trial sequential analysis to estimate the strength of evidence. We
      found 66 randomized trials. There was no statistically significant differences
      regarding mortality [relative risk (RR) 0.98; 95% confidence interval (CI) 0.66
      1.44], myocardial infarction (RR 0.95; 95% CI 0.65-1.37), or renewed coronary
      revascularization (RR 1.34; 95% CI 0.83-2.18). We found a significant reduced
      risk of atrial fibrillation (RR 0.69; 95% CI 0.57-0.83) and stroke (RR 0.53; 95%
      CI 0.31-0.91) in off-pump patients. However, when continuity correction for zero
      event trials was included, the reduction in stroke became insignificant (RR 0.62;
      95% CI 0.32-1.19). Trial sequential analysis demonstrated overwhelming evidence
      supporting that off-pump bypass surgery reduces atrial fibrillation. CONCLUSION:
      Off-pump surgery reduces the risks of postoperative atrial fibrillation compared
      with on-pump surgery. For death, myocardial infarction, stroke, and renewed
      coronary revascularization, the evidence is still weak and more low-bias risk
      trials are needed.

PMID- 18628262
TI  - Simulating the influence of vernalization, photoperiod and optimum temperature on
      wheat developmental rates.
AB  - BACKGROUND AND AIMS: Accurately representing development is essential for
      applying crop simulations to investigate the effects of climate, genotypes or
      crop management. Development in wheat (Triticum aestivum, T. durum) is primarily
      driven by temperature, but affected by vernalization and photoperiod, and is
      often simulated by reducing thermal-time accumulation using vernalization or
      photoperiod factors or limiting accumulation when a lower optimum temperature
      (T(optl)) is exceeded. In this study T(optl) and methods for representing effects
      of vernalization and photoperiod on anthesis were examined using a range of
      planting dates and genotypes. METHODS: An examination was made of T(optl) values
      of 15, 20, 25 and 50 degrees C, and either the most limiting or the
      multiplicative value of the vernalization and photoperiod development rate
      factors for simulating anthesis. Field data were from replicated trials at
      Ludhiana, Punjab, India with July through to December planting dates and seven
      cultivars varying in vernalization response. KEY RESULTS: Simulations of anthesis
      were similar for T(optl) values of 20, 25 and 50 degrees C, but a T(optl) of 15
      degrees C resulted in a consistent bias towards predicting anthesis late for
      early planting dates. Results for T(optl) above 15 degrees C may have occurred
      because mean temperatures rarely exceeded 20 degrees C before anthesis for many
      planting dates. For cultivars having a strong vernalization response, anthesis
      was more accurately simulated when vernalization and photoperiod factors were
      multiplied rather than using the most limiting of the two factors. CONCLUSIONS:
      Setting T(optl) to a high value (30 degrees C) and multiplying the vernalization
      and photoperiod factors resulted in accurately simulating anthesis for a wide
      range of planting dates and genotypes. However, for environments where average
      temperatures exceed 20 degrees C for much of the pre-anthesis period, a lower
      T(optl) (23 degrees C) might be appropriate. These results highlight the value of
      testing a model over a wide range of environments.

PMID- 18628264
TI  - John Bryant takes a closer look at some of this month's Original Articles.

PMID- 18628265
TI  - I.V. acetaminophen pharmacokinetics in neonates after multiple doses.
AB  - BACKGROUND: Pharmacokinetics of an i.v. prodrug of acetaminophen (propacetamol)
      in neonates after repeat dosing are reported, with scant data for i.v.
      acetaminophen formulation. METHODS: Neonates from an intensive care unit received
      6-hourly prn i.v. acetaminophen dosed according to postmenstrual age (PMA): 28-32
      weeks, 10 mg kg(-1); 32-36 weeks, 12.5 mg kg(-1); and > or =36 weeks, 15 mg kg(
      1). A maximum of five blood samples for assay and liver function tests (LFTs)
      were collected. A one-compartment linear disposition model (zero-order input;
      first-order elimination) was used to describe time-concentration profiles using
      population modelling (NONMEM). RESULTS: Fifty neonates, median (range) PMA 38.6
      (32-45) weeks, mean (SD) weight 2.9 (0.7) kg, received a mean of 15 doses over a
      median 4 days with 189 serum acetaminophen and 231 LFT measurements. Standardized
      population parameter estimates for a term neonate were clearance (CL) 5.24 (CV
      30.5%) litre h(-1) 70 kg(-1) and volume of distribution (V) 76 (29.6%) litre 70
      kg(-1). CL increased with PMA from 4.4 litre h(-1) 70 kg(-1) at 34 weeks to 6.3
      litre h(-1) 70 kg(-1) at 46 weeks. The presence of unconjugated
      hyperbilirubinaemia was associated with reduced CL: 150 micromol litre(-1)
      associated with 40% CL reduction. Acetaminophen concentrations between 10 and 23
      mg litre(-1) at steady state are predicted after 15 mg kg(-1) 6-hourly for a
      neonate of PMA 40 weeks. Hepatic enzyme analysis of daily samples changed
      significantly for one patient whose alanine aminotransferase concentration
      tripled. CONCLUSIONS: The parameter estimates are similar to those described for
      propacetamol. There was no evidence of hepatotoxicity. Unconjugated
      hyperbilirubinaemia impacts upon CL, dictating dose reduction.

PMID- 18628266
TI  - Measurement of surgical stress in anaesthetized children.
AB  - BACKGROUND: The surgical stress index (SSI), derived from a combination of heart
      rate (HR) and photoplethysmographic amplitude (PPGA) time series, is a novel
      method for continuous monitoring of intraoperative stress and has been validated
      in adults. The applicability of SSI and its constituents to monitoring children
      has not been previously evaluated. METHODS: In this controlled trial, 22
      anaesthetized patients, aged 4-17 yr, undergoing strabismus surgery were
      randomized into two groups, Group LL and Group BSS. Patients in Group LL received
      topical conjunctival anaesthesia with a 1:1 mixture of lidocaine 2% and
      levobupivacaine 0.75%, and patients in Group BSS received balanced salt solution.
      RESULTS: Endotracheal intubation (n=22) increased median (range) SSI from 39.2
      (22.6-55.6) to 53.6 (35.8-63.3) (P<0.001), decreased PPGA from 5.62 (2.79-9.69)
      to 5.27 (2.59-7.54)% (P=0.001), and increased the difference of response entropy
      (RE) and state entropy (SE) of frontal biopotentials (RE-SE) from 3.1 (0.06-9.1)
      to 5.7 (0.6-9.4) (P=0.01). Conventional haemodynamic variables also increased,
      median (range) HR from 72.9 (56.7-113.8) to 84.2 (60.4-124.8) beats min(-1)
      (P<0.001), and systolic non-invasive arterial pressure (S-NIBP) from 87 (78-143)
      to 103 (79-125) (P=0.007). When 3 min baseline before surgery was compared with
      12 min of surgery, median (range) SSI increased from 43.3 (31.2-58.0) to 49.9
      (39.3-57.2) (P=0.042) vs from 46.6 (26.8-57.8) to 52.1 (31.7-60.1) (P=0.024) and
      PPGA decreased from 6.60 (3.10-8.24) to 5.80 (3.03-7.65)% (P<0.001) vs from 5.51
      (3.25-9.84) to 5.06 (3.08-8.99)% (P=0.042), in Groups LL and BSS, respectively,
      but SSI or other indicators did not differ significantly between the groups.
      CONCLUSIONS: SSI, PPGA, HR, NIBP, RE, and RE-SE detect autonomic responses to
      nociceptive stimuli in anaesthetized children undergoing strabismus surgery.

PMID- 18628267
TI  - Contribution of violence to health inequalities in England: demographics and
      trends in emergency hospital admissions for assault.
AB  - INTRODUCTION: Violence is increasingly recognised as a major public health issue
      yet health data are underutilised for describing the problem or developing
      responses. We use English emergency hospital admissions for assault over four
      years to examine assault demography and contribution to health inequalities.
      METHODS: Geodemographic cross-sectional analyses utilising records of all
      individuals in England (n = 120 643) admitted between 1 April 2002 and 31 March
      2006. RESULTS: Over 4 years, rates of admission increased by 29.56% across
      England. Admissions peaked on Saturdays (22.34%) and Sundays (20.38%). Higher
      rates were associated with deprivation across all ages, including those <15
      years, with a sixfold increase in admission rates between the poorest and
      wealthiest quintiles of residence. Logistic regression analyses indicate males
      are 5.59 times more likely to be admitted to hospital for assault and such
      admissions peak in those aged 15-29 years. Modelling based on national assault
      admissions and limited Accident and Emergency (A&E) data suggest that while more
      serious assaults requiring hospital admission have increased, assault attendances
      at A&Es have fallen. DISCUSSION: Hospital admission and A&E data identify a
      direct contribution made by violence to health inequalities. Levels of violence
      inhibit other interventions to improve people's health through, for instance,
      outdoor exercise or delivery of health-related services in affected areas. With
      disproportionate exposure to violence in poorer areas even in those under 15,
      early life primary prevention initiatives are required in disadvantaged
      communities to reduce childhood harm and the development of adult perpetrators
      and victims of violence.

PMID- 18628268
TI  - Factors which nurture geographical resilience in Britain: a mixed methods study.
AB  - OBJECTIVES: To identify plausible mechanisms by which resilience (low mortality
      rates despite persistent economic adversity) was achieved in some areas in
      Britain between 1971 and 2001. METHODS: Mixed method observational study,
      combining quantitative analyses of cause- and age group-specific mortality rates,
      and area sociodemographic and environmental characteristics, with case studies of
      resilient areas which included in-depth interviews. RESULTS: The causes of death,
      and age groups, contributing most to resilience varied markedly between the 18
      resilient areas; as disease aetiology varies, a range of protective processes
      must be in operation. Four area characteristics, which plausibly contributed to
      resilience, emerged from the in-depth interviews: population composition;
      retaining or attracting population; environment and housing; and social cohesion.
      Quantitative analyses demonstrated significant difference between resilient and
      non-resilient areas in retaining or attracting population only. CONCLUSIONS:
      While we identified plausible area characteristics through which resilience was
      achieved, there does not appear to be a definitive set that reliably produces
      resilience, and resilient and non-resilient areas did not differ significantly in
      their possession of most of these characteristics. If such characteristics do
      have a role in creating resilience, but are present in both resilient and non
      resilient areas, further work is needed to explore what makes them "successful"
      in some areas, but not in others.

PMID- 18628269
TI  - The neighbourhood effects of geographical access to tobacco retailers on
      individual smoking behaviour.
AB  - OBJECTIVE: To investigate whether neighbourhood measures of geographical
      accessibility to outlets selling tobacco (supermarkets, convenience stores and
      petrol stations) are associated with individual smoking behaviour in New Zealand.
      METHODS: Using geographical information systems, travel times from the population
      weighted centroid of each neighbourhood to the closest outlet selling tobacco
      were calculated for all 38,350 neighbourhoods across New Zealand. These measures
      were appended to the 2002/03 New Zealand Health Survey, a national survey of 12,
      529 adults. Two-level logistic regression models were fitted to examine the
      effects of neighbourhood locational access upon individual smoking behaviour
      after controlling for potential individual- and neighbourhood-level confounding
      factors, including deprivation and urban/rural status. RESULTS: After controlling
      for individual-level demographic and socioeconomic variables, individuals living
      in the quartiles of neighbourhoods with the best access to supermarkets (OR 1.23,
      95% CI 1.06 to 1.42) and convenience stores (OR 1.19, 95% CI 1.03 to 1.38) had a
      higher odds of smoking compared with individuals in the worst access quartiles.
      However, the association between neighbourhood accessibility to supermarkets and
      convenience stores was not apparent once other neighbourhood-level variables
      (deprivation and rurality) were included. CONCLUSIONS: At the national level,
      there is little evidence to suggest that, after adjustment for neighbourhood
      deprivation, better locational access to tobacco retail provision in New Zealand
      is associated with individual-level smoking behaviour.

PMID- 18628270
TI  - Public injecting among a cohort of injecting drug users in Vancouver, Canada.
AB  - BACKGROUND: Despite the implementation of policy interventions to address open
      drug consumption, public injecting continues to occur in many urban settings.
      This study sought to examine public injecting among a community-recruited cohort
      of injecting drug users (IDUs) in Vancouver. METHODS: The prevalence and
      correlates of recent public injecting among participants enrolled in the
      Vancouver Injection Drug User Study during the period of 1 December 2003 to 30
      November 2005 were examined prospectively using generalised estimating equations
      (GEEs). RESULTS: Among the sample of 620 active IDUs, at some point during the
      study period, 142 (22.9%) individuals reported "usually" or "always" injecting in
      public in the 6 months prior to their study visit. Factors that were significant
      and positively associated with recent frequent public injecting in multivariate
      GEE analysis include homelessness (adjusted OR (AOR) 6.70); frequent crack use
      (AOR 1.48); and frequent heroin injection (AOR 1.56). Recent frequent public
      injecting was found to be negatively associated with cooking and filtering drugs
      prior to injecting (AOR 0.50) and older age (AOR 0.95). CONCLUSION: The findings
      indicate that a substantial proportion of local IDUs frequently inject in public,
      and those who report recently injecting in public spaces appear to be a
      vulnerable population facing significant health hazards. The provision of secure
      housing may have the potential to protect the health of IDUs in this setting and
      significantly decrease the prevalence of public injecting. In addition, the
      findings support previous work suggesting that removing barriers to the use of
      Vancouver's existing supervised injection site may serve to further reduce public
      drug use.

PMID- 18628271
TI  - Association between paternal schizophrenia and low birthweight: a nationwide
      population-based study.
AB  - Using a nationwide population-based dataset, the aim of the present study was to
      investigate the association between paternal schizophrenia and the risk of low
      birthweight (LBW). This study linked the 2001 Taiwan National Health Insurance
      Research Dataset with Taiwan's birth and death certificate registries. In total,
      220 465 singleton live births were included. The key dependent variable was
      whether or not an infant's father was diagnosed with schizophrenia, while the
      independent variable of interest was whether an infant had LBW. Multivariate
      logistic regression analysis was performed to explore the relationship between
      paternal schizophrenia and the risk of LBW, after adjusting for the infant and
      parents' characteristics. The results show that infants whose fathers had
      schizophrenia were more likely to have LBW than those whose fathers did not
      (12.6% vs 8.0%). Infants whose fathers had schizophrenia were found to be 1.58
      (95% confidence interval = 1.10-2.52, P < .05) times more likely to have LBW than
      their counterparts whose fathers did not have schizophrenia, following adjustment
      for gestational week at birth, parity, paternal age and highest educational
      level, family monthly incomes, and marital status. We conclude that the offspring
      whose fathers had a diagnosis of schizophrenia had increased risk of LBW compared
      with those whose fathers had no schizophrenia. This finding paves the way for
      further studies and suggests that there may be potential benefit to early
      intervention to prevent LBW in pregnant women with husbands with schizophrenia.

PMID- 18628272
TI  - Reinforcement and reversal learning in first-episode psychosis.
AB  - BACKGROUND: Abnormalities in reinforcement learning and reversal learning have
      been reported in psychosis, possibly secondary to subcortical dopamine
      abnormalities. METHODS: We studied simple discrimination (SD) learning and
      reversal learning in a sample of 119 first-episode psychosis patients from the
      Cambridge early psychosis service (CAMEO) and 107 control participants. We used
      data on reinforcement learning and reversal learning extracted from the Cambridge
      Neuropsychological Test Automated Battery Intradimensional-Extradimensional shift
      task, which measures cognitive flexibility but also involves simple reinforcement
      learning (SD learning) and reversal learning stages. We also gathered diagnostic
      information to examine whether there were any differences between patients
      ultimately diagnosed with schizophrenia-spectrum disorders and those diagnosed
      with affective psychosis. RESULTS: Psychosis patients demonstrated deficits in
      simple reinforcement learning (SD learning) and in reversal learning, with no
      differences between affective psychosis and schizophrenia-spectrum psychosis.
      There was a significant modest correlation between reversal errors and negative
      symptoms (Spearman rho = 0.3, P = .02). CONCLUSIONS: There are reinforcement
      learning abnormalities in first-episode psychosis, which correlate with negative
      symptoms, suggesting a possible role for orbitofrontal cortex and ventral
      striatal pathology in the pathogenesis of motivational deficits in psychosis.

PMID- 18628274
TI  - Using quality improvement methods to improve public health emergency
      preparedness: PREPARE for Pandemic Influenza.
AB  - Many public health departments seek to improve their capability to respond to
      large-scale events such as an influenza pandemic. Quality improvement (QI), a
      structured approach to improving performance, has not been widely applied in
      public health. We developed and tested a pilot QI collaborative to explore
      whether QI could help public health departments improve their pandemic
      preparedness. We demonstrated that this is a promising model for improving public
      health preparedness and may be useful for improving public health performance
      overall. Further efforts are needed, however, to encourage the robust
      implementation of QI in public health.

PMID- 18628273
TI  - The genetics of symptom-based phenotypes: toward a molecular classification of
      schizophrenia.
AB  - OBJECTIVE: Genetic linkage studies in schizophrenia (SZ) have primarily focused
      on the phenotype of disease susceptibility. A limited number of studies, however,
      have reported suggestive linkage to specific SZ symptom domains including regions
      on chromosomes 6, 8, and 20. We examined these chromosomal regions for
      association to positive, negative, and disorganized symptom clusters, using a
      dense set of single-nucleotide polymorphisms (SNPs). METHODS: We ascertained 178
      Caucasian patients with SZ for lifetime severity of clinical symptomatology using
      a structured diagnostic interview. The cohort was genotyped with the Affymetrix
      500K microarray, from which we selected, a priori, 4833 intragenic SNPs located
      within chromosomal regions previously linked to specific SZ symptom clusters.
      Parametric tests, corrected for multiple testing, were used to compare the
      effects of allelic variation within these SNPs to the lifetime severity of the
      specific symptom domain that had been implicated by prior linkage studies.
      RESULTS: We were able to extend previous reports of linkage between chromosome 6q
      and both positive and disorganized symptoms. Lifetime severity of positive
      symptoms was significantly (P = 2.50 x 10(-5)) associated with a SNP within the
      origin recognition complex subunit 3-like (ORC3L) gene, a gene implicated in
      synaptic plasticity. Level of disorganized symptoms was significantly (P < 6.00 x
      10(-5)) associated 2 SNPs within the brain-specific angiogenesis inhibitor 3
      (BAI3) gene, which is highly expressed in brain during development. CONCLUSIONS:
      These data point toward specific candidate genes located within previously
      implicated linkage peaks for clinical symptomatology. Identification of
      functional variants within these regions and a characterization of the effect of
      these risk genotypes on the treatment of specific clinical symptoms are needed.

PMID- 18628275
TI  - Improvement in circulation and in cardiovascular risk factors with a proprietary
      isotonic bioflavonoid formula OPC-3.
AB  - This study investigated the efficacy of isotonic bioflavonoid supplementation,
      OPC-3 on 61 individuals presenting with risk factors meeting the criteria for
      metabolic syndrome. Subjects were supplemented with a proprietary isotonic
      bioflavonoid OPC-3 or placebo over 2 months. Plasma oxidative stress status was
      significantly lowered by 10.1% with OPC-3. All major cardiovascular risk factors
      were improved with blood pressure, total cholesterol, and fasting blood glucose
      lowered. OPC-3 significantly improved endothelial function as evaluated by
      increased vasorelaxation in reactive hyperemia and enhanced diastolic carotid
      artery flow. Cardiac ultrasound scanning revealed a significant increase of left
      ventricular ejection fraction. Skin microcirculation was enhanced, and better
      tissue perfusion led to significantly increased transcutaneous oxygen partial
      pressure and decreased pCO(2). With OPC-3 a dramatic and significant plasma C
      reactive protein decrease by 52.1% occurred. Individuals may improve key
      cardiovascular risk factors by daily supplementation with the bioflavonoid OPC-3
      as an important part of a healthier lifestyle.

PMID- 18628276
TI  - Rosuvastatin and cardiovascular disease: did the strongest statin hold the
      initial promises?
AB  - Rosuvastatin is the latest and most potent statin currently on the market. It has
      the greatest efficacy compared with all other available statins on total
      cholesterol and low-density lipoprotein cholesterol (LDL-C) reduction, and also
      provides a significant increase in high-density lipoprotein cholesterol (HDL-C)
      better than atorvastatin. Imaging studies showed a regression of atheroma in
      secondary prevention patients using an intravascular ultrasound technique and a
      hold of progression in primary prevention patients using carotid intima-media
      thickness as a surrogate marker. The JUPITER trial, a primary prevention large
      scale, prospective study to examine the role of statin therapy in individuals
      with raised C-reactive protein but normal LDL-C levels, was recently terminated
      early due to a significant reduction of events in the rosuvastatin group.
      Rosuvastatin has held its initial promises as a very potent statin, with
      favourable effects on HDL, showing a regression or a halt of the atherosclerotic
      burden and reducing cardiovascular events in low-risk patients.

PMID- 18628277
TI  - Endothelial injury and repair: a novel theory for atherosclerosis.
AB  - The traditional view of atherosclerosis as a pathological lipid deposition within
      the artery wall has been redefined by a more complex theory in which the presence
      of a dysfunctional endothelium plays a pivotal role. The discovery of progenitor
      cells of myeloid origin, which are able to replace old or injured mature
      endothelial cells and are able to differentiate into healthy and functional
      endothelial cells, has offered the prospect of merging the traditional theories
      on the pathogenesis of atherosclerosis with the evolving concept of a role of
      these progenitor cells in the repair of the injured vessel wall and the
      neovascularization of ischemic tissues. This article summarizes current knowledge
      about the biology of atherosclerosis with emphasis on the balance between
      endothelial injury and repair and on the concept that the turnover and
      replacement of endothelial cells is a major determinant in the maintenance of
      vascular integrity.

PMID- 18628278
TI  - Carotid intima-media thickness (cIMT): a useful clinic tool or research luxury?
      Another view of the ENHANCE trial.
AB  - The ENHANCE trial was the first trial of ezetimibe- simvastatin with a surrogate
      marker as a primary endpoint. The combination of the 2 drugs is highly effective
      in reducing total cholesterol and low-density lipoprotein cholesterol levels and
      with a positive profile on high-density lipoprotein cholesterol. However, there
      are no data as yet about the clinical effectiveness of the addition of ezetimibe
      on statin therapy and whether this provides a further reduction of cardiovascular
      events. The answer to the clinical hard endpoints question will be provided in
      2012 by the IMPROVE-IT trial comparing the effectiveness of simvastatin 40 mg
      plus ezetimibe versus simvastatin 40 mg on 18,000 acute coronary syndrome
      patients. The ENHANCE study failed in its primary endpoint, carotid intima-media
      thickness reduction, but has various methodological weaknesses that makes it very
      difficult to accept the American College of Cardiology statement that ezetimibe
      should be the last resort after trying all other available treatments.

PMID- 18628279
TI  - Proceedings of the 23rd International Congress of Cardiology organized by the
      Hellenic Heart Foundation: May 1-3, 2008 Athens, Greece.

PMID- 18628280
TI  - Seven models of population obesity.
AB  - Obesity is new in human evolutionary history, having become possible at the
      population level with increased food security. As with any phenotype, obesity is
      at base an outcome of gene-environment interactions. However, different
      disciplines working in obesity research have identified different facets of the
      problem and developed different models of population obesity. These include those
      of thrifty genotypes, obesogenic behavior, obesogenic environments, nutrition
      transition, obesogenic culture, and biocultural interactions of genetics,
      environment, behavior, and culture. Although there is an overlap between various
      of these models, there remains a lack of consensus concerning obesity causation
      at the population level. This is a major problem in study of, and intervention
      in, obesity among populations.

PMID- 18628281
TI  - The role of audiologic evaluation in progressive audiologic tinnitus management.
AB  - Progressive Audiologic Tinnitus Management (PATM) is based on the premise that
      tinnitus is managed most efficiently using a hierarchy of clinical services that
      address different levels of need. PATM includes five levels of management: (a)
      triage; (b) audiologic evaluation; (c) group education; (d) tinnitus evaluation;
      and (e) individualized management. This article provides an overview of PATM and
      focuses on the procedures that make up the Level 2 Audiologic Evaluation. The
      evaluation is conducted to assess the potential need for medical, audiologic
      (hearing loss, tinnitus, hyperacusis), and/or mental health services. The
      Tinnitus Handicap Inventory, Hearing Handicap Inventory, and Tinnitus and Hearing
      Survey are used to differentiate effects of tinnitus and hearing loss. If
      indicated, patients are interviewed with the Tinnitus-Impact Screening Interview.
      Patients requiring amplification receive hearing aids. Often, management of
      hearing loss at Level 2 addresses any problems that were attributed to the
      tinnitus, which obviates further tinnitus-specific intervention.

PMID- 18628283
TI  - Physical function in ankylosing spondylitis is independently determined by both
      disease activity and radiographic damage of the spine.
AB  - AIM: To study the relationship between disease activity, radiographic damage and
      physical function in patients with ankylosing spondylitis (AS) PATIENTS AND
      METHODS: Baseline and 2-year data of the Outcome in Ankylosing Spondylitis
      International Study (OASIS)(217 patients) were used. Physical function was
      expressed by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the
      Dougados Functional Index (DFI); disease activity by the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) and by erythrocyte sedimentation rate
      and C-reactive protein; and structural damage by the modified Stoke Ankylosing
      Spondylitis Spine Score (mSASSS). Syndesmophyte- and non-syndesmophyte sum cores,
      and numbers of affected (bridged) vertebral units were derived from the mSASSS.
      Univariate correlations were calculated on baseline values using the Spearman
      rank correlation. Multivariate associations were investigated by generalised
      estimating equations (GEE) on baseline and 2-year data. RESULTS: mSASSS
      correlated moderately well with BASFI (Spearman's r = 0.45) and DFI (r = 0.38).
      BASDAI correlated well with BASFI (r = 0.66) and DFI (r = 0.59). Correlation
      coefficients for mSASSS versus BASFI and DFI decreased by increasing levels of
      BASDAI, being zero at the highest quintile of BASDAI. GEE showed that both BASDAI
      and mSASSS independently and significantly helped to explain either BASFI or DFI.
      Results were similar for syndesmophyte sum score, non-syndesmophyte sum score,
      number of affected VUs or number of VUs with bridging. The lumbar part of the
      mSASSS contributed similarly to the cervical part in explaining BASFI/DFI.
      CONCLUSION: Physical function impairment in AS is independently caused by patient
      reported disease activity and the level of structural damage of the lumbar and
      cervical spine. Syndesmophytes and other radiographic abnormalities contribute to
      physical function impairment.

PMID- 18628282
TI  - Thymic function in juvenile idiopathic arthritis.
AB  - OBJECTIVE: Thymic function declines exponentially with age. Impaired thymic
      function has been associated with autoimmune disease in adults but has never been
      formally assessed in childhood autoimmunity. Therefore, thymic function in
      children with the autoimmune disease juvenile idiopathic arthritis (JIA) was
      determined. METHODS: Thymic function was measured in 70 children and young adults
      with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls
      using four independent assays. T cell receptor excision circles (WBLogTREC/ml)
      and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic
      emigrants; %RTEs) were quantified and intrathymic proliferation measured by
      calculating the alphaTREC/SigmabetaTREC ratio. Lastly, regulatory T cells
      (T(Reg)) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to
      assess the ability of the thymus in JIA to generate this T cell subset. RESULTS:
      Thymic function was equivalent by all four parameters in JIA when compared with
      the control population. Furthermore, there was no consistent effect of JIA
      subtype on thymic function, although intrathymic proliferation was higher in the
      small rheumatoid factor (RF)(+) polyarticular group. There were no significant
      effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids
      on thymic function, although those with the worst prognostic ILAR (International
      League of Associations for Rheumatology) subtypes were also those most likely to
      be on a DMARD. CONCLUSIONS: It is demonstrated that children and young adults
      with JIA, unlike adults with autoimmune diseases, have thymic function that is
      comparable with that of healthy controls. The varied pathologies represented by
      the term "JIA" suggest this observation may not be disease specific and raises
      interesting questions about the aetiology of thymic impairment in adult
      autoimmunity.

PMID- 18628284
TI  - Increased serum levels of B cell activating factor (BAFF) in subsets of patients
      with idiopathic inflammatory myopathies.
AB  - OBJECTIVE: To investigate serum levels of B cell activating factor (BAFF) in
      patients with myositis and correlate these to autoantibody profile, clinical
      phenotype and treatment. METHODS: BAFF levels in sera from 49 patients with
      dermatomyositis, 44 with polymyositis, 6 with inclusion body myositis and 30
      matched controls were measured by ELISA. Specific autoantibodies were detected by
      line blot and western blot assays. RESULTS: Serum levels of BAFF were
      significantly higher in patients compared to healthy controls (p = 0.003).
      Patients with anti-Jo-1 autoantibodies had higher BAFF levels than control
      individuals (p<0.003) or patients without any specific autoantibodies (p<0.05).
      Patients with dermatomyositis had higher BAFF levels compared to polymyositis
      (p<0.05). Patients with interstitial lung disease (ILD) had higher BAFF levels
      than patients without ILD (p<0.05) or controls (p<0.01) but this could be
      explained by presence of anti-Jo-1 autoantibodies. BAFF levels correlated with
      serum creatine kinase (CK) (rs = 0.365, p = 0.0005) but not with C-reactive
      protein (CRP) levels. A negative correlation of BAFF levels with glucocorticoid
      daily dose for all patients (rs = -0.292, p = 0.003) and with cumulative
      glucocorticoid doses in early myositis cases (rs = -0.659, p<0.001) was recorded.
      CONCLUSION: Our finding of elevated serum levels of BAFF in patients with
      myositis with described phenotypes together with the correlations between levels
      of BAFF and CK and a negative correlation with dose of glucocorticoids, indicate
      that BAFF could be a potential therapeutic target in such cases.

PMID- 18628285
TI  - Regulation of CXCL16 expression and secretion by myeloid cells is not altered in
      rheumatoid arthritis.
AB  - OBJECTIVE: Chemokine (C-X-C motif) ligand 16 (CXCL16) is secreted by macrophages
      and dendritic cells (DCs) to attract memory type T cells. CXCL16 expression is
      increased in arthritic joints of patients with rheumatoid arthritis (RA) and a
      role for CXCL16 has been suggested in the pathogenesis of RA. To date, little is
      known about the regulation of CXCL16 on monocytes/macrophages and DCs. The aim of
      this study was to elucidate how CXCL16 expression is regulated in healthy donors
      and patients with RA. METHODS: CD14+cells were isolated from the peripheral blood
      or synovial fluid of patients with RA and healthy controls, differentiated into
      different types of dendritic cells or macrophages and stimulated with various
      cytokines or lipopolysaccharide (LPS). Cell surface proteins, including surface
      CXCL16, were measured by flow cytometry and soluble CXCL16 was measured by ELISA.
      RESULTS: Distinct types of dendritic cells constitutively express and secrete
      CXCL16, which is not affected by maturation. Monocytes rapidly upregulate
      membrane-bound CXCL16 expression and release soluble CXCL16 upon culture. CXCL16
      expression by monocytes is transiently inhibited by the Toll-like receptor (TLR)4
      ligand LPS. Th2 type cytokines inhibit soluble CXCL16, whereas T helper (Th)1
      cell stimulus enhances its release. In RA monocytes/macrophages, neither CXCL16
      expression, nor CXCL16 regulation is different from healthy controls.
      CONCLUSIONS: Culture of monocytes is the main trigger for CXCL16 surface
      expression in vitro, which is not altered in RA. Together our data suggest that
      the increased CXCL16 expression in patients with RA is likely to be caused by
      increased influx of monocytes rather than intrinsic differences in CXCL16
      regulation.

PMID- 18628286
TI  - Decreased capillary permeability and capillary density in patients with systemic
      sclerosis using large-window sodium fluorescein videodensitometry of the ankle.
AB  - OBJECTIVE: Local capillary permeability in patients with SSc has been reported
      increased when assessed by nail-fold capillaroscopy. We measured capillary
      permeability at a clinically less affected site by using large-window fluorescein
      videodensitometry of the ankle. We hypothesized that increased capillary
      permeability or leakage is a generalized phenomenon in SSc. METHODS: Large-window
      videodensitometry with sodium fluorescein was performed in 38 SSc patients and 20
      healthy controls. Capillary permeability was expressed as the average relative
      light intensity over the first 7 min [I(av)(7)] after appearance of fluorescein
      in skin capillaries. RESULTS: Capillary permeability, expressed as I(av)(7) was
      significantly decreased in patients with SSc (47.3 +/- 15.0% vs 57.6 +/- 9.4% in
      controls, P = 0.007), as was capillary density (12 +/- 6/mm(2) vs 26 +/-
      11/mm(2), P < 0.001). Adjustment for capillary density in multivariate regression
      analysis demonstrated that differences in I(av)(7) between SSc patients and
      controls were related to differences in capillary density, BMI and high density
      lipoprotein cholesterol. CONCLUSION: At the level of the ankle decreased
      capillary permeability was found in SSc patients, related to decreased capillary
      density. Microvascular involvement in SSc is widespread, but no evidence was
      established for increased capillary permeability at the level of individual
      capillaries as a generalized phenomenon.

PMID- 18628287
TI  - Tolerability of methotrexate and leflunomide combination therapy for inflammatory
      arthritis in routine clinical practice: results of a four-centre study.

PMID- 18628289
TI  - PathCluster: a framework for gene set-based hierarchical clustering.
AB  - MOTIVATION: Gene clustering and gene set-based functional analysis are widely
      used for the analysis of expression profiles. The development of a comprehensive
      method jointly combining the two methods would allow for greater biological
      insights. RESULTS: We developed a software package, PathCluster for gene set
      based clustering via an agglomerative hierarchical clustering algorithm. The
      distances between predefined gene sets are illustrated in a dendrogram in which
      the relationships between gene sets can be visually assessed. Valuable biological
      insights can be obtained according to the type of gene sets, e.g. coordinated
      action of molecular functions (functional gene sets) and putative motif synergy
      (promoter gene set) in a biological process. The combined use of gene sets
      further enables the interrogation of different biological themes and their
      putative relationships, such as function-versus-regulatory motif or drug-versus
      function. PathCluster can also be used for knowledge-based sample partitioning or
      class categorization for clinical purposes. With extended applicability,
      PathCluster will facilitate the gleaning of meaningful biological insights and
      testable hypotheses in the contexts of given expression profiles. AVAILABILITY:
      PathCluster executable files can be freely downloaded at
      http://www.systemsbiology.co.kr/PathCluster/.

PMID- 18628288
TI  - The wisdom of the commons: ensemble tree classifiers for prostate cancer
      prognosis.
AB  - MOTIVATION: Classification and regression trees have long been used for cancer
      diagnosis and prognosis. Nevertheless, instability and variable selection bias,
      as well as overfitting, are well-known problems of tree-based methods. In this
      article, we investigate whether ensemble tree classifiers can ameliorate these
      difficulties, using data from two recent studies of radical prostatectomy in
      prostate cancer. RESULTS: Using time to progression following prostatectomy as
      the relevant clinical endpoint, we found that ensemble tree classifiers robustly
      and reproducibly identified three subgroups of patients in the two clinical
      datasets: non-progressors, early progressors and late progressors. Moreover, the
      consensus classifications were independent predictors of time to progression
      compared to known clinical prognostic factors.

PMID- 18628290
TI  - Artificial neural network for prediction of antigenic activity for a major
      conformational epitope in the hepatitis C virus NS3 protein.
AB  - MOTIVATION: Insufficient knowledge of general principles for accurate
      quantitative inference of biological properties from sequences is a major
      obstacle in the rationale design of proteins with predetermined activities. Due
      to this deficiency, protein engineering frequently relies on the use of
      computational approaches focused on the identification of quantitative structure
      activity relationship (SAR) for each specific task. In the current article, a
      computational model was developed to define SAR for a major conformational
      antigenic epitope of the hepatitis C virus (HCV) non-structural protein 3 (NS3)
      in order to facilitate a rationale design of HCV antigens with improved
      diagnostically relevant properties. RESULTS: We present an artificial neural
      network (ANN) model that connects changes in the antigenic properties and
      structure of HCV NS3 recombinant proteins representing all 6 HCV genotypes. The
      ANN performed quantitative predictions of the enzyme immunoassay (EIA)
      Signal/Cutoff (S/Co) profiles from sequence information alone with 89.8%
      accuracy. Amino acid positions and physicochemical factors strongly associated
      with the HCV NS3 antigenic properties were identified. The positions most
      significantly contributing to the model were mapped on the NS3 3D structure. The
      location of these positions validates the major associations found by the ANN
      model between antigenicity and structure of the HCV NS3 proteins. AVAILABILITY:
      Matlab code is available at the following URL address: http://bio
      ai.myeweb.net/box_widget.html

PMID- 18628291
TI  - Hit selection with false discovery rate control in genome-scale RNAi screens.
AB  - RNA interference (RNAi) is a modality in which small double-stranded RNA
      molecules (siRNAs) designed to lead to the degradation of specific mRNAs are
      introduced into cells or organisms. siRNA libraries have been developed in which
      siRNAs targeting virtually every gene in the human genome are designed,
      synthesized and are presented for introduction into cells by transfection in a
      microtiter plate array. These siRNAs can then be transfected into cells using
      high-throughput screening (HTS) methodologies. The goal of RNAi HTS is to
      identify a set of siRNAs that inhibit or activate defined cellular phenotypes.
      The commonly used analysis methods including median +/- kMAD have issues about
      error rates in multiple hypothesis testing and plate-wise versus experiment-wise
      analysis. We propose a methodology based on a Bayesian framework to address these
      issues. Our approach allows for sharing of information across plates in a plate
      wise analysis, which obviates the need for choosing either a plate-wise or
      experimental-wise analysis. The proposed approach incorporates information from
      reliable controls to achieve a higher power and a balance between the
      contribution from the samples and control wells. Our approach provides false
      discovery rate (FDR) control to address multiple testing issues and it is robust
      to outliers.

PMID- 18628292
TI  - Specific ligation to double-stranded RNA for analysis of cellular RNA::RNA
      interactions.
AB  - Double-stranded RNA (dsRNA) is formed in cells as intra- and intermolecular RNA
      interactions and is involved in a range of biological processes including RNA
      metabolism, RNA interference and translation control mediated by natural
      antisense RNA and microRNA. Despite this breadth of activities, few molecular
      tools are available to analyse dsRNA as native hybrids. We describe a two-step
      ligation method for enzymatic joining of dsRNA adaptors to any dsRNA molecule in
      its duplex form without a need for prior sequence or termini information. The
      method is specific for dsRNA and can ligate various adaptors to label, map or
      amplify dsRNA sequences. When combined with reverse transcription-polymerase
      chain reaction, the method is sensitive and can detect low nanomolar
      concentrations of dsRNA in total RNA. As examples, we mapped dsRNA/single
      stranded RNA junctions within Escherichia coli hok mRNA and the human
      immunodeficiency virus TAR element using RNA from bacteria and mammalian cells.

PMID- 18628293
TI  - Processing of triplex-directed psoralen DNA interstrand crosslinks by
      recombination mechanisms.
AB  - Gene targeting via homologous recombination (HR) is an important application in
      biotechnology and medicine. However, in mammalian cells HR is much less efficient
      than random integration. Triplex-forming oligonucleotides (TFOs) linked to DNA
      damaging agents (e.g. psoralen) can stimulate HR, providing the potential to
      improve gene therapy applications. To elucidate factors affecting TFO-directed
      psoralen interstrand crosslink (ICL)-induced recombination, we constructed a
      series of plasmids with duplicated supF reporter genes, each containing an
      inactivating deletion, to measure HR frequencies in mammalian cells. Our results
      indicated that TFO-directed ICL-induced recombination frequencies were higher in
      the plasmids with larger distances between duplicated supF genes than with a
      smaller separation distance. However, the position of the ICL relative to the
      reporter genes did not affect HR frequencies. Recombination spectra were altered
      by the distance between supF copies. Although single-strand annealing (SSA)
      recombinants were predominant in all plasmid substrates, the plasmid with the
      shortest interval (60 bp) revealed a significant proportion of gene conversions
      (GCs). GCs occurred exclusively in the gene containing the shortest deletion,
      regardless of the distance between supF genes, ICL position or deletion
      orientation. Our analyses indicated that SSA is the predominant mechanism of ICL
      processing of these substrates in mammalian cells.

PMID- 18628294
TI  - Electrical detection of the temperature induced melting transition of a DNA
      hairpin covalently attached to gold interdigitated microelectrodes.
AB  - The temperature induced melting transition of a self-complementary DNA strand
      covalently attached at the 5' end to the surface of a gold interdigitated
      microelectrode (GIME) was monitored in a novel, label-free, manner. The
      structural state of the hairpin was assessed by measuring four different
      electronic properties of the GIME (capacitance, impedance, dissipation factor and
      phase angle) as a function of temperature from 25 degrees C to 80 degrees C.
      Consistent changes in all four electronic properties of the GIME were observed
      over this temperature range, and attributed to the transition of the attached
      single-stranded DNA (ssDNA) from an intramolecular, folded hairpin structure to a
      melted ssDNA. The melting curve of the self-complementary single strand was also
      measured in solution using differential scanning calorimetry (DSC) and UV
      absorbance spectroscopy. Temperature dependent electronic measurements on the
      surface and absorbance versus temperature values measured in solution experiments
      were analyzed assuming a two-state process. The model analysis provided estimates
      of the thermodynamic transition parameters of the hairpin on the surface. Two
      state analyses of optical melting data and DSC measurements provided evaluations
      of the thermodynamic transition parameters of the hairpin in solution. Comparison
      of surface and solution measurements provided quantitative evaluation of the
      effect of the surface on the thermodynamics of the melting transition of the DNA
      hairpin.

PMID- 18628295
TI  - Functional studies on transfected cell microarray analysed by linear regression
      modelling.
AB  - Transfected cell microarray is a promising method for accelerating the functional
      exploration of the genome, giving information about protein function in the
      living cell. The microarrays consist of clusters of cells (spots) overexpressing
      or silencing a particular gene product. The subsequent analysis of the phenotypic
      consequences of such perturbations can then be detected using cell-based assays.
      The focus in the present study was to establish an experimental design and a
      robust analysis approach for fluorescence intensity data, and to address the use
      of replicates for studying regulation of gene expression with varying complexity
      and effect size. Our analysis pipeline includes measurement of fluorescence
      intensities, normalization strategies using negative control spots and internal
      control plasmids, and linear regression (ANOVA) modelling for estimating
      biological effects and calculating P-values for comparisons of interests. Our
      results show the potential of transfected cell microarrays in studying complex
      regulation of gene expression by enabling measurement of biological responses in
      cells with overexpression and downregulation of specific gene products, combined
      with the possibility of assaying the effects of external stimuli. Simulation
      experiments show that transfected cell microarrays can be used to reliably detect
      even quantitatively minor biological effects by including several technical and
      experimental replicates.

PMID- 18628296
TI  - DNA methylation analysis by digital bisulfite genomic sequencing and digital
      MethyLight.
AB  - Alterations in cytosine-5 DNA methylation are frequently observed in most types
      of human cancer. Although assays utilizing PCR amplification of bisulfite
      converted DNA are widely employed to analyze these DNA methylation alterations,
      they are generally limited in throughput capacity, detection sensitivity, and or
      resolution. Digital PCR, in which a DNA sample is analyzed in distributive
      fashion over multiple reaction chambers, allows for enumeration of discrete
      template DNA molecules, as well as sequestration of non-specific primer annealing
      templates into negative chambers, thereby increasing the signal-to-noise ratio in
      positive chambers. Here, we have applied digital PCR technology to bisulfite
      converted DNA for single-molecule high-resolution DNA methylation analysis and
      for increased sensitivity DNA methylation detection. We developed digital
      bisulfite genomic DNA sequencing to efficiently determine single-basepair DNA
      methylation patterns on single-molecule DNA templates without an interim cloning
      step. We also developed digital MethyLight, which surpasses traditional
      MethyLight in detection sensitivity and quantitative accuracy for low quantities
      of DNA. Using digital MethyLight, we identified single-molecule, cancer-specific
      DNA hypermethylation events in the CpG islands of RUNX3, CLDN5 and FOXE1 present
      in plasma samples from breast cancer patients.

PMID- 18628297
TI  - Human DDX3 functions in translation and interacts with the translation initiation
      factor eIF3.
AB  - The conserved RNA helicase DDX3 is of major medical importance due to its
      involvement in numerous cancers, human hepatitis C virus (HCV) and HIV. Although
      DDX3 has been reported to have a wide variety of cellular functions, its precise
      role remains obscure. Here, we raised a new antibody to DDX3 and used it to show
      that DDX3 is evenly distributed throughout the cytoplasm at steady state.
      Consistent with this observation, HA-tagged DDX3 also localizes to the cytoplasm.
      RNAi of DDX3 in both human and Drosophila cells shows that DDX3 is required for
      cell viability. Moreover, using RNAi, we show that DDX3 is required for
      expression of protein from reporter constructs. In contrast, we did not detect a
      role for DDX3 in nuclear steps in gene expression. Further insight into the
      function of DDX3 came from the observation that its major interaction partner is
      the multi-component translation initiation factor eIF3. We conclude that a
      primary function for DDX3 is in protein translation, via an interaction with
      eIF3.

PMID- 18628298
TI  - Partial reconstitution of DNA large loop repair with purified proteins from
      Saccharomyces cerevisiae.
AB  - Small looped mispairs are corrected by DNA mismatch repair. In addition, a
      distinct process called large loop repair (LLR) corrects heteroduplexes up to
      several hundred nucleotides in bacteria, yeast and human cells, and in cell-free
      extracts. Only some LLR protein components are known, however. Previous studies
      with neutralizing antibodies suggested a role for yeast DNA polymerase delta (Pol
      delta), RFC and PCNA in LLR repair synthesis. In the current study, biochemical
      fractionation studies identified FEN1 (Rad27) as another required LLR component.
      In the presence of purified FEN1, Pol delta, RFC and PCNA, repair occurred on
      heteroduplexes with loops ranging from 8 to 216 nt. Repair utilized a 5' nick,
      with correction directed to the nicked strand, irrespective of which strand
      contained the loop. In contrast, repair of a G/T mismatch occurred at low levels,
      suggesting specificity of the reconstituted system for looped mispairs. The
      presence of RPA enhanced reactivity on some looped substrates, but RPA was not
      required for activity. Although additional LLR factors remain to be identified,
      the excision and resynthesis steps of LLR from a 5' nick can be reconstituted in
      a purified system with FEN1 and Pol delta, together with PCNA and its loader RFC.

PMID- 18628300
TI  - Live cell imaging and electron microscopy reveal dynamic processes of BAF
      directed nuclear envelope assembly.
AB  - Assembly of the nuclear envelope (NE) in telophase is essential for higher
      eukaryotic cells to re-establish a functional nucleus. Time-lapse, FRAP and FRET
      analyses in human cells showed that barrier-to-autointegration factor (BAF), a
      DNA-binding protein, assembled first at the distinct ;core' region of the
      telophase chromosome and formed an immobile complex by directly binding with
      other core-localizing NE proteins, such as lamin A and emerin. Correlative light
      and electron microscopy after live cell imaging, further showed that BAF formed
      an electron-dense structure on the chromosome surface of the core, close to
      spindle microtubules (MTs) prior to the attachment of precursor NE membranes,
      suggesting that MTs may mediate core assembly of BAF. Disruption of the spindle
      MTs consistently abolished BAF accumulation at the core. In addition, RNAi of BAF
      eliminated the core assembly of lamin A and emerin, caused abnormal cytoplasmic
      accumulation of precursor nuclear membranes and resulted in a significant delay
      of NE assembly. These results suggest that the MT-mediated BAF accumulation at
      the core facilitates NE assembly at the end of mitosis.

PMID- 18628301
TI  - Divergent polarization mechanisms during vertebrate epithelial development
      mediated by the Crumbs complex protein Nagie oko.
AB  - The zebrafish MAGUK protein Nagie oko is a member of the evolutionarily conserved
      Crumbs protein complex and functions as a scaffolding protein involved in the
      stabilization of multi-protein assemblies at the tight junction. During zebrafish
      embryogenesis, mutations in nagie oko cause defects in both epithelial polarity
      and cardiac morphogenesis. We used deletion constructs of Nagie oko in functional
      rescue experiments to define domains essential for cell polarity, maintenance of
      epithelial integrity and cardiac morphogenesis. Inability of Nagie oko to
      interact with Crumbs proteins upon deletion of the PDZ domain recreates all
      aspects of the nagie oko mutant phenotype. Consistent with this observation,
      apical localization of Nagie oko within the myocardium and neural tube is
      dependent on Oko meduzy/Crumbs2a. Disruption of direct interactions with Patj or
      Lin-7, two other members of the Crumbs protein complex, via the bipartite L27
      domains produces only partial nagie oko mutant phenotypes and does not impair
      correct junctional localization of the truncated Nagie oko deletion protein
      within myocardial cells. Similarly, loss of the evolutionarily conserved region 1
      domain, which mediates binding to Par6, causes only a subset of the nagie oko
      mutant epithelial phenotypes. Finally, deletion of the C-terminus, including the
      entire guanylate kinase and the SH3 domains, renders the truncated Nagie oko
      protein inactive and recreates all features of the nagie oko mutant phenotype
      when tested in functional complementation assays. Our observations reveal a
      previously unknown diversity of alternative multi-protein assembly compositions
      of the Crumbs-Nagie-oko and Par6-aPKC protein complexes that are highly dependent
      on the developmental context.

PMID- 18628302
TI  - Identification of two partners from the bacterial Kef exchanger family for the
      apical plasma membrane V-ATPase of Metazoa.
AB  - The vital task of vectorial solute transport is often energised by a plasma
      membrane, proton-motive V-ATPase. However, its proposed partner, an apical alkali
      metal/proton exchanger, has remained elusive. Here, both FlyAtlas microarray data
      and in situ analyses demonstrate that the bacterial kefB and kefC (members of the
      CPA2 family) homologues in Drosophila, CG10806 and CG31052, respectively, are
      both co-expressed with V-ATPase genes in transporting epithelia.
      Immunocytochemistry localises endogenous CG10806 and CG31052 to the apical plasma
      membrane of the Malpighian (renal) tubule. YFP-tagged CG10806 and CG31052 both
      localise to the plasma membrane of Drosophila S2 cells, and when driven in
      principal cells of the Malpighian tubule, they localise specifically to the
      apical plasma membrane. V-ATPase-energised fluid secretion is affected by
      overexpression of CG10806, but not CG31052; in the former case, overexpression
      causes higher basal rates, but lower stimulated rates, of fluid secretion
      compared with parental controls. Overexpression also impacts levels of secreted
      Na+ and K+. Both genes rescue exchanger-deficient (nha1 nhx1) yeast, but act
      differently; CG10806 is driven predominantly to the plasma membrane and confers
      protection against excess K+, whereas CG31052 is expressed predominantly on the
      vacuolar membrane and protects against excess Na+. Thus, both CG10806 and CG31052
      are functionally members of the CPA2 gene family, colocalise to the same apical
      membrane as the plasma membrane V-ATPase and show distinct ion specificities, as
      expected for the Wieczorek exchanger.

PMID- 18628303
TI  - Ca2+ oscillation frequency regulates agonist-stimulated gene expression in
      vascular endothelial cells.
AB  - A physiological membrane-receptor agonist typically stimulates oscillations, of
      varying frequencies, in cytosolic Ca2+ concentration ([Ca2+]i). Whether and how
      [Ca2+]i oscillation frequency regulates agonist-stimulated downstream events,
      such as gene expression, in non-excitable cells remain unknown. By precisely
      manipulating [Ca2+]i oscillation frequency in histamine-stimulated vascular
      endothelial cells (ECs), we demonstrate that the gene expression of vascular cell
      adhesion molecule 1 (VCAM1) critically depends on [Ca2+]i oscillation frequency
      in the presence, as well as the absence, of histamine stimulation. However,
      histamine stimulation enhanced the efficiency of [Ca2+]i-oscillation-frequency
      regulated VCAM1 gene expression, versus [Ca2+]i oscillations alone in the absence
      of histamine stimulation. Furthermore, a [Ca2+]i oscillation frequency previously
      observed to be the mean frequency in histamine-stimulated ECs was found to
      optimize VCAM1 mRNA expression. All the above effects were abolished or
      attenuated by blocking histamine-stimulated generation of intracellular reactive
      oxygen species (ROS), another intracellular signaling pathway, and were restored
      by supplementary application of a low level of H2O2. Endogenous NF-kappaB
      activity is similarly regulated by [Ca2+]i oscillation frequency, as well as its
      co-operation with ROS during histamine stimulation. This study shows that [Ca2+]i
      oscillation frequency cooperates with ROS to efficiently regulate agonist
      stimulated gene expression, and provides a novel and general strategy for
      studying [Ca2+]i signal kinetics in agonist-stimulated downstream events.

PMID- 18628304
TI  - An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells.
AB  - Androgen-androgen-receptor (androgen-AR) signaling in normal prostate epithelium
      promotes terminal luminal epithelial cell differentiation. In androgen-dependent
      prostate-cancer cells, androgen-AR signaling gains the ability to promote both
      differentiation and proliferation. How this signaling promotes proliferation of
      androgen-dependent prostate-cancer cells and its relationship with the
      differentiation-promoting functions of the AR are important issues regarding the
      biology of androgen-dependent prostate-cancer cells. Herein, we report the
      identification of an AR-Skp2 pathway in prostate-cancer cells that depend on the
      AR for proliferation; in this pathway, AR is a robust upstream regulator of Skp2
      through blocking the D-box-dependent degradation of this protein, and Skp2, in
      turn, serves as an essential downstream effector of AR in promoting proliferation
      independently of the differentiation-promoting function of AR. These results
      provide new knowledge on how AR functions in androgen-dependent prostate-cancer
      cells and identify strategies to specifically target the proliferation-promoting
      function of AR without compromising cancer-cell differentiation.

PMID- 18628305
TI  - EGF induces coalescence of different lipid rafts.
AB  - The suggestion that microdomains may function as signaling platforms arose from
      the presence of growth factor receptors, such as the EGFR, in biochemically
      isolated lipid raft fractions. To investigate the role of EGFR activation in the
      organization of lipid rafts we have performed FLIM analyses using putative lipid
      raft markers such as ganglioside GM1 and glycosylphosphatidylinositol (GPI)
      anchored GFP (GPI-GFP). The EGFR was labeled using single domain antibodies from
      Llama glama that specifically bind the EGFR without stimulating its kinase
      activity. Our FLIM analyses demonstrate a cholesterol-independent colocalization
      of GM1 with EGFR, which was not observed for the transferrin receptor. By
      contrast, a cholesterol-dependent colocalization was observed for GM1 with GPI
      GFP. In the resting state no colocalization was observed between EGFR and GPI
      GFP, but stimulation of the cell with EGF resulted in the colocalization at the
      nanoscale level of EGFR and GPI-GFP. Moreover, EGF induced the enrichment of GPI
      GFP in a detergent-free lipid raft fraction. Our results suggest that EGF induces
      the coalescence of the two types of GM1-containing microdomains that might lead
      to the formation of signaling platforms.

PMID- 18628306
TI  - Characterization of the mitochondrial protein LETM1, which maintains the
      mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L.
AB  - LETM1 is located in the chromosomal region that is deleted in patients suffering
      Wolf-Hirschhorn syndrome; it encodes a homolog of the yeast protein Mdm38 that is
      involved in mitochondrial morphology. Here, we describe the LETM1-mediated
      regulation of the mitochondrial volume and its interaction with the mitochondrial
      AAA-ATPase BCS1L that is responsible for three different human disorders. LETM1
      is a mitochondrial inner-membrane protein with a large domain extruding to the
      matrix. The LETM1 homolog LETM2 is a mitochondrial protein that is expressed
      preferentially in testis and sperm. LETM1 downregulation caused mitochondrial
      swelling and cristae disorganization, but seemed to have little effect on
      membrane fusion and fission. Formation of the respiratory-chain complex was
      impaired by LETM1 knockdown. Cells lacking mitochondrial DNA lost active
      respiratory chains but maintained mitochondrial tubular networks, indicating that
      mitochondrial swelling caused by LETM1 knockdown is not caused by the disassembly
      of the respiratory chains. LETM1 was co-precipitated with BCS1L and formation of
      the LETM1 complex depended on BCS1L levels, suggesting that BCS1L stimulates the
      assembly of the LETM1 complex. BCS1L knockdown caused disassembly of the
      respiratory chains as well as LETM1 downregulation and induced distinct changes
      in mitochondrial morphology.

PMID- 18628308
TI  - aPKC enables development of zonula adherens by antagonizing centripetal
      contraction of the circumferential actomyosin cables.
AB  - Atypical protein kinase C (aPKC) generally plays crucial roles in the
      establishment of cell polarity in various biological contexts. In mammalian
      epithelial cells, aPKC essentially works towards the transition of primordial
      spot-like adherens junctions (AJs) into continuous belt-like AJs, also called
      zonula adherens, lined with perijunctional actin belts. To reveal the mechanism
      underlying this aPKC function, we investigated the functional relationship
      between aPKC and myosin II, the essential role of which in epithelial-junction
      development was recently demonstrated. Despite its deleterious effects on
      junction formation, overexpression of a dominant-negative mutant of aPKC (aPKC
      lambda kn) did not interfere with the initial phase of myosin-II activation
      triggered by the formation of Ca2+-switch-induced cell-cell contacts.
      Furthermore, cells overexpressing aPKC lambda kn exhibited myosin-II-dependent
      asymmetric organization of F-actin along the apicobasal axis, suggesting that
      aPKC contributes to junction development without affecting the centripetal
      contraction of the circumferential actomyosin cables. Time-lapse analyses using
      GFP-actin directly revealed that the circumferential actomyosin cables were
      centrifugally expanded and developed into perijunctional actin belts during
      epithelial polarization, and that aPKClambda kn specifically compromised this
      process. Taken together, we conclude that aPKC is required for antagonizing the
      myosin-II-driven centripetal contraction of the circumferential actin cables,
      thereby efficiently coupling the myosin-II activity with junction development and
      cell polarization. The present results provide novel insights into not only the
      site of action of aPKC kinase activity but also the role of actomyosin
      contraction in epithelial polarization.

PMID- 18628307
TI  - Laminin alpha 5 influences the architecture of the mouse small intestine mucosa.
AB  - The mammalian intestine displays two distinct patterns of mucosal organization.
      The small intestine contains mucosal epithelial invaginations (the crypts of
      Lieberkuhn) that are continuous with evaginations (villi) into the lumen. The
      colon also contains crypts of Lieberkuhn, but its epithelial surface is lined by
      flat surface cuffs. The epithelial cells of both organs communicate with the
      underlying mesenchyme through a basement membrane that is composed of a variety
      of extracellular matrix proteins, including members of the laminin family. The
      basement membranes of the small intestine and colon contain distinct laminin
      subtypes; notably, the villus basement membrane is rich in laminin alpha 5. Here,
      we show that the diminution of laminin alpha 5 in a mouse model led to a
      compensatory deposition of colonic laminins, which resulted in a transformation
      from a small intestinal to a colonic mucosal architecture. The alteration in
      mucosal architecture was associated with reduced levels of nuclear p27Kip1 - a
      cell-cycle regulator - and altered intestinal epithelial cell proliferation,
      migration and differentiation. Our results suggest that laminin alpha 5 has a
      crucial role in establishing and maintaining the specific mucosal pattern of the
      mouse small intestine.

PMID- 18628309
TI  - Slk19-dependent mid-anaphase pause in kinesin-5-mutated cells.
AB  - We examined spindle elongation in anaphase in Saccharomyces cerevisiae cells
      mutated for the kinesin-5 motor proteins Cin8 and Kip1. Cells were deleted for
      KIP1 and/or expressed one of two motor-domain Cin8 mutants (Cin8-F467A or Cin8
      R196K, which differ in their ability to bind microtubules in vitro, with Cin8
      F467A having the weakest ability). We found that, in kinesin-5-mutated cells,
      predominantly in kip1 Delta cin8-F467A cells, anaphase spindle elongation was
      frequently interrupted after the fast phase, resulting in a mid-anaphase pause.
      Expression of kinesin-5 mutants also caused an asymmetric midzone location and
      enlarged midzone size, suggesting that proper organization of the midzone is
      required for continuous spindle elongation. We also examined the effects of
      components of the FEAR pathway, which is involved in the early-anaphase
      activation of Cdc14 regulatory phosphatase, on anaphase spindle elongation in
      kip1 Delta cin8-F467A cells. Deletion of SLK19, but not SPO12, eliminated the mid
      anaphase pause, caused premature anaphase onset and defects in DNA division
      during anaphase, and reduced viability in these cells. Finally, overriding of the
      pre-anaphase checkpoint by overexpression of Cdc20 also eliminated the mid
      anaphase pause and caused DNA deformation during anaphase in kip1 Delta cin8
      F467A cells. We propose that transient activation of the pre-anaphase checkpoint
      in kinesin-5-mutated cells induces a Slk19-dependent mid-anaphase pause, which
      might be important for proper DNA segregation.

PMID- 18628311
TI  - Mapping of 5q35 chromosomal rearrangements within a genomically unstable region.
AB  - BACKGROUND: Recent molecular studies of breakpoints of recurrent chromosome
      rearrangements revealed the role of genomic architecture in their formation. In
      particular, segmental duplications representing blocks of >1 kb with >90%
      sequence homology were shown to mediate non-allelic homologous recombination
      (NAHR). However, the occurrence of the majority of newly detected submicroscopic
      imbalances cannot be explained by the presence of segmental duplications.
      Therefore, further studies are needed to investigate whether architectural
      features other than segmental duplications mediate these rearrangements. METHODS:
      We analysed a series of patients with breakpoints clustering within chromosome
      band 5q35. Using high density arrays and subsequent quantitative polymerase chain
      reaction (qPCR), we characterised the breakpoints of four interstitial deletions
      (including one associated with an unbalanced paracentric inversion), a
      duplication and a familial reciprocal t(5;18)(q35;q22) translocation. RESULTS AND
      CONCLUSION: Five of the breakpoints were located within an interval of
      approximately 265 kb encompassing the RANBP17 and TLX3 genes. This region is also
      targeted by the recurrent cryptic t(5;14)(q35;q32) translocation, which occurs in
      approximately 20% of childhood T cell acute lymphoblastic leukaemia (T-ALL). In
      silico analysis indicated the architectural features most likely to contribute to
      the genomic instability of this region, which was supported by our molecular
      data. Of further interest, in two patients and the familial translocation, the
      delineated breakpoint regions encompassed highly homologous LINEs (long
      interspersed nuclear elements), suggesting that NAHR between these LINEs may have
      mediated these rearrangements.

PMID- 18628310
TI  - Regulation of Kalirin by Cdk5.
AB  - Kalirin, one of the few Rho guanine nucleotide exchange factors (GEFs) that
      contains spectrin-like repeats, plays a critical role in axon extension and
      maintenance of dendritic spines. PC12 cells were used to determine whether Cdk5,
      a critical participant in both processes, regulates the action of Kalirin.
      Expression of Kalirin-7 in nondifferentiated PC12 cells caused GEF-activity
      dependent extension of broad cytoplasmic protrusions; coexpression of dominant
      negative Cdk5 largely eliminated this response. The spectrin-like repeat region
      of Kalirin plays an essential role in this response, which is not mimicked by the
      GEF domain alone. Thr1590, which follows the first GEF domain of Kalirin, is the
      only Cdk5 phosphorylation site in Kalirin-7. Although mutant Kalirin-7 with
      Ala1590 retains GEF activity, it is unable to cause extension of protrusions.
      Kalirin-7 with an Asp1590 mutation has slightly increased GEF activity and
      dominant-negative Cdk5 fails to block its ability to cause extension of
      protrusions. Phosphorylation of Thr1590 causes a slight increase in GEF activity
      and Kalirin-7 solubility. Dendritic spines formed by cortical neurons in response
      to the expression of Kalirin-7 with Ala1590 differ in shape from those formed in
      response to wild-type Kalirin-7 or Kalirin-7 containing Asp1590. The presence of
      Thr1590 in each major Kalirin isoform would allow Cdk5 to regulate Kalirin
      function throughout development.

PMID- 18628312
TI  - Epigenetic analysis of the critical region I for premature ovarian failure:
      demonstration of a highly heterochromatic domain on the long arm of the mammalian
      X chromosome.
AB  - BACKGROUND: X chromosome rearrangements defined a critical region for premature
      ovarian failure (POF) that extended for >15 Mb in Xq. It has been shown
      previously that the region could be divided into two functionally distinct
      portions and suggested that balanced translocations interrupting its proximal
      part, critical region 1 (CR1), could be responsible for POF through
      downregulation of ovary expressed autosomal genes translocated to the X
      chromosome. RESULTS AND CONCLUSION: This study reports that such position effect
      can indeed be demonstrated by analysis of breakpoint regions in somatic cells of
      POF patients and by the finding that CR1 has a highly heterochromatic
      organisation, very different from that of the euchromatic autosomal regions
      involved in the rearrangements. The chromatin organisation of the POF CR1 is
      likely to be responsible for the epigenetic modifications observed in POF
      patients. The characteristics of CR1 and its downregulation in oocytes may very
      well explain its role in POF and the frequency of the POF phenotype in
      chromosomal rearrangements involving Xq. This study also demonstrates a large and
      evolutionary conserved domain of the long arm of the X chromosome, largely
      corresponding to CR1, that may have structural or functional roles, in oocyte
      maturation or in X chromosome inactivation.

PMID- 18628313
TI  - Cerebro-oculo-facio-skeletal syndrome: three additional cases with CSB mutations,
      new diagnostic criteria and an approach to investigation.
AB  - BACKGROUND: The cerebro-oculo-facio-skeletal syndrome (COFS syndrome) is an
      autosomal recessive disorder which was initially described in a specific
      aboriginal population from Manitoba. In recent years, COFS syndrome has been
      linked in this original population to a defective DNA repair pathway and to a
      homozygous mutation in the major gene underlying Cockayne syndrome (CSB).
      However, most reports of suspected COFS syndrome outside this population have not
      been confirmed at the molecular level, leading to considerable heterogeneity
      within the syndrome and confusing overlaps between COFS syndrome and other eye
      and brain disorders. OBJECTIVE: To refine the delineation of the syndrome on
      genetically proven COFS cases. METHODS: We report the exhaustive clinical,
      cellular and molecular data of three unrelated COFS patients with mutations in
      the CSB gene. RESULTS: All three patients present the cardinal features of COFS
      syndrome including extreme microcephaly, congenital cataracts, facial dysmorphism
      and arthrogryposis. They also exhibit a predominantly postnatal growth failure, a
      severe psychomotor retardation, with axial hypotonia and peripheral hypertonia
      and neonatal feeding difficulties. Fibroblasts from the patients show the same
      DNA repair defect which can be complemented by transfection of the CSB wild-type
      cDNA. Five new mutations in the CSB gene have been identified in these patients.
      CONCLUSIONS: Our data indicate that COFS syndrome represents the most severe end
      of the Cockayne spectrum. New diagnostic criteria for COFS syndrome are proposed,
      based on our findings and on the few genetically proven COFS cases from the
      literature.

PMID- 18628314
TI  - Alteration of expression of muscle specific isoforms of the fragile X related
      protein 1 (FXR1P) in facioscapulohumeral muscular dystrophy patients.
AB  - BACKGROUND: The Fragile X Mental retardation-Related 1 (FXR1) gene belongs to the
      fragile X related family, that also includes the Fragile X Mental Retardation
      (FMR1) gene involved in fragile X syndrome, the most common form of inherited
      mental retardation. While the absence of FMRP impairs cognitive functions,
      inactivation of FXR1 has been reported to have drastic effects in mouse and
      xenopus myogenesis. Seven alternatively spliced FXR1 mRNA variants have been
      identified, three of them being muscle specific. Interestingly, they encode FXR1P
      isoforms displaying selective RNA binding properties. METHODS AND RESULTS: Since
      facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy
      characterised by altered splicing of mRNAs encoding muscle specific proteins, we
      have studied the splicing pattern of FXR1 mRNA in myoblasts and myotubes of FSHD
      patients. We show here that FSHD myoblasts display an abnormal pattern of
      expression of FXR1P isoforms. Moreover, we provide evidence that this altered
      pattern of expression is due to a specific reduced stability of muscle specific
      FXR1 mRNA variants, leading to a reduced expression of FXR1P muscle specific
      isoforms. CONCLUSION: Our data suggest that the molecular basis of FSHD not only
      involves splicing alterations, as previously proposed, but may also involve a
      deregulation of mRNA stability. In addition, since FXR1P is an RNA binding
      protein likely to regulate the metabolism of muscle specific mRNAs during
      myogenesis, its altered expression in FSHD myoblasts may contribute to the
      physiopathology of this disease.

PMID- 18628316
TI  - A phase i study of bolus 5-fluorouracil and leucovorin combined with weekly
      paclitaxel (FLTAX) as first-line therapy for advanced gastric cancer.
AB  - OBJECTIVE: To determine the dose-limiting toxicity (DLT) and the maximum
      tolerated dose (MTD) of combination chemotherapy with leucovorin-modulated weekly
      bolus 5-fluorouracil (5-FU) and weekly paclitaxel in patients with advanced
      gastric cancer (GC). METHODS: Chemotherapy-naive patients with histologically
      proven metastatic or recurrent GC were enrolled. Paclitaxel was administered as a
      1-h intravenous (i.v.) infusion followed by 5-FU as a bolus i.v. infusion on Days
      1, 8 and 15. A 2-h i.v. infusion of l-leucovorin was started at the same time as
      the paclitaxel infusion on Days 1, 8 and 15. Treatment cycles were repeated every
      28 days until disease progression or unacceptable toxicity occurred. Patients
      were scheduled to receive 5-FU, l-leucovorin and paclitaxel at four dose levels
      (mg/m(2)/week): 500/250/60 (level 1), 500/250/80 (level 2), 600/250/80 (level 3)
      and 600/250/100 (level 4), respectively. RESULTS: Eighteen patients were
      enrolled. During the first cycle of the highest dose level (level 4), two of the
      six patients had DLT involving Grade 3 diarrhea and Grade 3 skin rash.
      Furthermore, three of the four patients who received the second consecutive cycle
      of treatment at dose level 4 had Grade 4 neutropenia. Dose level 3 was thus
      determined to be the MTD. Eleven (61%) of the 18 patients had partial responses,
      and the median progression-free survival time was 6.8 months. CONCLUSIONS: The
      MTD and the recommended dose for phase II studies of this regimen were determined
      to be 5-FU 600 mg/m(2)/week, l-leucovorin 250 mg/m(2)/week and paclitaxel 80
      mg/m(2)/week.

PMID- 18628315
TI  - Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.
AB  - BACKGROUND: The chromosome 17q21.31 microdeletion syndrome is a novel genomic
      disorder that has originally been identified using high resolution genome
      analyses in patients with unexplained mental retardation. AIM: We report the
      molecular and/or clinical characterisation of 22 individuals with the 17q21.31
      microdeletion syndrome. RESULTS: We estimate the prevalence of the syndrome to be
      1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical
      examination reveals that developmental delay, hypotonia, facial dysmorphisms
      including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and
      a friendly/amiable behaviour are the most characteristic features. Other
      clinically important features include epilepsy, heart defects and kidney/urologic
      anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31
      critical region to a 424 kb genomic segment (chr17: 41046729-41470954, hg17)
      encompassing at least six genes, among which is the gene encoding microtubule
      associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with
      a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the
      recurrent deletion, failed to identify any disease associated variants. In five
      deletion carriers we identify a <500 bp rearrangement hotspot at the proximal
      breakpoint contained within an L2 LINE motif and show that in every case examined
      the parent originating the deletion carries a common 900 kb 17q21.31 inversion
      polymorphism, indicating that this inversion is a necessary factor for deletion
      to occur (p<10(-5)). CONCLUSION: Our data establish the 17q21.31 microdeletion
      syndrome as a clinically and molecularly well recognisable genomic disorder.

PMID- 18628317
TI  - Ten year trends in chronic disease risk factors in the Republic of Karelia,
      Russia.
AB  - BACKGROUND: In Russia, non-communicable diseases are leading cause of death. The
      aim of this article is to describe changes in chronic disease risk factors (RFs)
      in Pitkaranta district in Russia during ten year period of time from 1992 to
      2002. METHODS: Study areas were Pitkaranta and Aunus districts in the Republic of
      Karelia, North-West Russia. The RF surveys were carried out in Pitkaranta every
      fifth year since 1992 and in Aunus in 2003. Independent random samples, age 25
      64, were taken from the population registers. Blood pressure, weight and height
      were measured. Serum cholesterol, HDL-cholesterol, triglyceride and GGT values
      were determined from serum samples. Smoking and alcohol consumption were asked.
      The total number of respondents was 2766. RESULTS: Systolic and diastolic blood
      pressure decreased in Pitkaranta from 1992 to 2002. Total serum cholesterol
      increased slightly. There was no significant change in BMI or in physical
      activity. Smoking did not change in males but increased among females. Self
      reported alcohol use increased, as also mean GGT. CONCLUSIONS: The study gives
      valuable information on developments of RFs in Russia. Some alarming tendencies
      in lifestyle were seen and chronic disease RF situation has generally worsened.
      The results also show how big is the challenge to change lifestyles deep in
      culture--and in the situation where preventive work and policies do not receive
      strong support. A reliable monitoring of RFs and behaviours is obviously a back
      bone for drawing necessary attention and to steer intervention.

PMID- 18628319
TI  - Identifying patients with peripheral-type early non-small cell lung cancer
      (T1N0M0) for whom irradiation of the primary focus alone could lead to successful
      treatment.
AB  - We investigated the indication of radiotherapy in operable patients with
      peripheral-type early non-small cell lung cancer (T1N0M0 (TNM staging in 1997)).
      The subjects comprised 396 patients with non-small cell lung cancer in whom the
      clinical stage was evaluated as IA. We examined age, gender, Brinkmann's index,
      histopathological type, the grade of histopathological differentiation, tumour
      diameter and the level of carcinoembryonic antigen as factors involved in lymph
      node metastasis. Lymph node metastasis was detected in 79 patients (20%). Factors
      such as the grade of histopathological differentiation and tumour diameter were
      involved in lymph node metastasis. In well-differentiated lesions, the
      probability of metastasis was <10% even when the tumour diameter exceeded 2 cm.
      However, the probability rapidly increased with tumour size in moderately and
      poorly differentiated lesions. Among the patients with peripheral-type early non
      small cell lung cancer (T1N0M0), the risk of lymph node metastasis was low in
      those with well-differentiated carcinoma and those with moderately differentiated
      lesions measuring </=1.5 cm in diameter. The proportion of our patients fitting
      these criteria was approximately 30%. For these patients, stereotactic body
      radiotherapy and particle therapy may be indicated.

PMID- 18628320
TI  - Dosimetric comparison of 106Ru and 125I plaques for treatment of shallow (<or=5
      mm) choroidal melanoma lesions.
AB  - The aim of this study was to compare dosimetric parameters between iodine-125
      ((125)I) and ruthenium-106 ((106)Ru) plaques of similar sizes in the treatment of
      choroidal melanomas. The study design included retrospective double planning of
      each case. 26 consecutive patients with choroidal melanomas measuring 5 mm or
      less in thickness were included. Dose distributions were calculated using Plaque
      Simulator treatment-planning software for a prescription of 85 Gy to the tumour
      apex. Doses to the outer sclera, lens, fovea and optic disc were obtained for
      each case using appropriately sized plaques of each isotope. Statistical
      inferences were made using the non-parametric Wilcoxon signed rank test. The mean
      dose to the macula, disc and lens was 18%, 53% and 89% less, respectively, with
      (106)Ru than with (125)I. Scleral doses were greater for (106)Ru. The use of
      collaborative ocular melanoma study dosimetry results in even higher mean doses
      to the macula, disc, lens and sclera. Two-dimensional dose distributions and dose
      volume histograms demonstrated the increase in dose outside the tumour volume
      using (125)I. This comparison shows that, for tumours not exceeding 5 mm in
      thickness, the use of (106)Ru plaques has the potential to reduce the radiation
      dose to nearby normal structures and possibly lower the risk of radiation-induced
      visual loss.

PMID- 18628318
TI  - Education in relation to incidence of and mortality from cancer and
      cardiovascular disease in Japan.
AB  - BACKGROUND: Although lower education has been associated with poorer health, few
      studies have examined whether lower education affects mortality, incidence, both
      or neither of cancer and cardiovascular disease. METHODS: The authors conducted a
      population-based prospective cohort study among 39,228 men and women who were
      aged 40-59 years and lived in four areas in Japan. Information on education and
      lifestyle variables were obtained by a self-administered questionnaire in 1990.
      Follow-up until the end of 2002 (for incidence) or 2003 (for mortality)
      ascertained 2573 and 1251 incident cases of cancer and cardiovascular disease,
      respectively, and 2430 deaths (1064 from cancer, 548 from cardiovascular disease
      and 818 from other causes). RESULTS: After adjustment for demographic and
      lifestyle variables, <10 years of education, as compared with >12 years of
      education, was associated with significantly higher mortality from all causes
      [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.05-1.42] and
      cardiovascular disease (HR = 1.44, 95% CI: 1.01-2.06), but was not associated
      with higher incidence of cardiovascular disease (HR = 0.96, 95% CI: 0.78-1.18) or
      higher mortality or incidence of cancer. CONCLUSION: The findings suggest that
      lower education is associated with higher mortality from all causes and
      cardiovascular disease among the Japanese population that is not totally
      attributable to lifestyle differences or higher cardiovascular disease incidence.

PMID- 18628321
TI  - Can we afford not to implement in vivo dosimetry?

PMID- 18628322
TI  - The effect of voice recognition software on comparative error rates in radiology
      reports.
AB  - This study sought to confirm whether reports generated in a department of
      radiology contain more errors if generated using voice recognition (VR) software
      than if traditional dictation-transcription (DT) is used. All radiology reports
      generated over a 1-week period in a British teaching hospital were assessed. The
      presence of errors and their impact on the report were assessed. Data collected
      included the type of report, site of dictation, the experience of the operator,
      and whether English was the first language of the operator. 1887 reports were
      reviewed. 1160 (61.5%) were dictated using VR and 727 reports (38.5%) were
      generated by DT. 71 errors (3.8% of all reports) were identified. 56 errors were
      made using VR (4.8% of VR reports), whereas 15 errors were identified in DT
      reports (2.1% of transcribed reports). The difference in report errors between
      these two dictation methods was statistically significant (p = 0.002). Of the 71
      reports containing errors, 37 (52.1%) had errors that affecting understanding.
      Other factors were also identified that significantly increased the likelihood of
      errors in a VR-generated report, such as working in a busy inpatient environment
      (p<0.001) and having a language other than English as a first language (p =
      0.034). Operator grade was not significantly associated with increased errors. In
      conclusion, using VR significantly increases the number of reports containing
      errors. Errors using VR are significantly more likely to occur in noisy areas
      with a high workload and are more likely to be made by radiologists for whom
      English is not their first language.

PMID- 18628323
TI  - Congenital cystic adenomatoid malformation (Type II) with active tuberculosis in
      an adult.
AB  - Cystic adenomatoid malformation (CAM) is a congenital disorder similar to
      bronchopulmonary sequestration. Most cases of CAM are diagnosed during the
      neonatal period and infancy. The histological classification of the vast majority
      of reported cases of CAM is Stocker's Type I. We present an adult patient with
      Stocker's Type II CAM with active tuberculosis.

PMID- 18628324
TI  - Mucoid impaction secondary to mucin-producing metastatic adenocarcinoma of the
      cervix.
AB  - Endobronchial metastases are an uncommon complication of malignant tumours. The
      vast majority are secondary to carcinoma of the breast, colorectum and kidney, or
      to melanoma. Occasionally, endobronchial tumours can result in partial or
      complete bronchial obstruction. Here, we describe an uncommon case of
      endobronchial metastasis of adenocarcinoma of the cervix causing mucoid impaction
      owing to mucous production by the tumour cells.

PMID- 18628325
TI  - Rare coincidence of congenital short and annular pancreas with gallbladder
      agenesis and splenic malrotation.
AB  - We present an adult patient with anomalies of congenital short and annular
      pancreas, gallbladder agenesis and splenic malrotation. The patient presented
      with symptoms typical of the two pancreatic malformations and is the only
      reported case with these malformations reported in the English imaging
      literature.

PMID- 18628326
TI  - Ossifying lipoma of the thigh.
AB  - Lipomas are common soft-tissue tumours that are usually found in the subcutaneous
      adipose tissue. Occasionally, they may contain mesenchymal elements other than
      adipose tissue, including osseous components. These ossifying lipomas are usually
      located near or within bone, and it is very rare for a lipoma with no connection
      to bone to contain mature osseous tissue. We describe a case of a symptomatic
      ossifying intramuscular lipoma of the thigh.

PMID- 18628327
TI  - Focal extramedullary haematopoiesis of the spleen: unusual MR appearance with
      pathological correlation.
AB  - We report the unusual MR appearance of focal extramedullary haematopoiesis (EMH)
      of the spleen in a 72-year-old man with thrombocytopenia. Variable MR signal
      characteristics of EMH, which depend upon the amount of fat and the level of
      haematopoietic activity, have been described previously. We believe, however,
      that the delayed central enhancement of EMH on MRI findings was exceptional and
      has not been reported previously. After pathological investigation and
      correlation, we believe that the central zone containing hypocellular collagenous
      bundles may account for this specific enhancement.

PMID- 18628328
TI  - Duplicated right coronary artery: multidetector CT angiographic findings.
AB  - Multidetector CT is becoming an alternative method for the diagnosis of coronary
      artery anomalies. We present the multidetector coronary CT angiography findings
      from a patient with right coronary artery duplication. Two separate right
      coronary arteries originating from the right aortic sinus were observed. Their
      anatomical course was well depicted, and atherosclerosis was excluded based on
      the CT angiography findings.

PMID- 18628329
TI  - The technology of MRI--the next 10 years?
AB  - MRI is the most flexible of our diagnostic imaging modalities, possessing the
      ability to characterize a wide range of parameters in the living subject and
      provide exquisite spatial resolution. Here we first review the rise of MRI to its
      current clinical "state-of-the-art" status and then consider the future
      directions for this technique. The long-term impact on clinical practice of
      recent innovations in MRI scanner hardware and sequence design are also
      considered. Key changes in clinical practice that we predict for the coming 10
      years include: a widespread shift to higher field imaging (3T); further
      improvements in MRI coil technology, including further increases in the number of
      channels; the introduction of ultra-short echo-time imaging; the introduction of
      combined modality methods (e.g. positron emission tomography (PET)-MRI and single
      photon emission CT (SPECT)-MRI); and significant advances in molecular MRI
      agents. Even after 30 years of continuing developments in human MRI, the coming
      decade will provide further major advances in diagnostic MRI.

PMID- 18628330
TI  - Gastrointestinal stromal tumours: CT findings.
AB  - The aim of this study was to identify the predictors of malignancy and to
      demonstrate the uncommon radiological features of gastrointestinal stromal
      tumours (GIST) using CT. 30 patients participated in this retrospective study. CT
      findings were evaluated by two radiologists, and categorical variables were
      compared using chi(2) or Fisher's exact tests. These tests were used to assess
      any possible relationships between mitotic index and (i) tumour location, size,
      contour and growth status, (ii) presence of calcifications, necrosis or
      lymphadenopathy, (iii) enhancement pattern, (iv) metastasis to the liver or other
      distant sites and (v) invasion of the mesentery or adjacent organs. Tumours were
      located in the stomach (n = 22), small bowel (n = 6) and colon (n = 2). The size,
      localization, enhancement pattern, metastasis to the liver or other distant sites
      and the cystic-necrotic component of the tumours were all associated with a high
      mitotic index in statistical analyses (p<0.05). Uncommon radiological findings
      seen on CT were saccular aneurysmal dilatation, malignant lymphadenopathy and
      satellite nodules. In conclusion, CT features of GISTs were helpful in
      identifying predictors of malignant behaviour.

PMID- 18628331
TI  - MRI in patients with chronic obstructive uropathy and compromised renal function:
      a sole method for morphological and functional assessment.
AB  - The aim of this study was to assess the role of MRI as a single modality for
      anatomical and functional evaluation of obstructed kidneys in patients with
      compromised renal function. The study included 96 adults with unilateral or
      bilateral chronic obstructive hydronephrosis and compromised renal function
      (serum creatinine >or=1.8 mg dl(-1)). Patients were subjected to gadolinium
      enhanced MRI (Gd-MRI), which determined the anatomy of both renoureteral units,
      as well as their function, through selective calculation of the glomerular
      filtration rate (GFR) of each kidney. All patients underwent a technetium-99m
      diethylenetriamine-pentaacetic acid renal scan. Moreover, a correlation was made
      between the GFR determined by Gd-MRI and the isotope GFR. The study comprised 59
      males and 37 females. A comprehensive MRI study detected the cause of obstruction
      in all kidneys with non-calcular obstruction (sensitivity of 100%) and in 21
      kidneys with calcular obstruction (sensitivity of 70%). The overall sensitivity
      of MRI combined with plain X-ray of the abdomen and ultrasound in the detection
      of various causes of obstruction was 97%. A comparison between the isotope GFR of
      the obstructed kidneys and the corresponding magnetic resonance urography (MRU)
      GFR showed perfect correlation. In conclusion, combined static and dynamic MRU is
      a promising technique that allows anatomical and functional evaluation of
      obstructed kidneys in patients with impaired renal function but, owing to the
      possible risk of nephrogenic systemic fibrosis in patients with a GFR <30 ml min(
      1), the lowest possible dose of the most stable Gd-macrocyclic chelates should be
      used if a functional MRI study is required.

PMID- 18628332
TI  - Distinct lymph nodal sonographic characteristics in breast cancer patients at
      high risk for axillary metastases correlate with the final axillary stage.
AB  - The purpose of this study was to assess the clinical relevance, limitations and
      most common findings of axillary ultrasound and subsequent image-guided
      aspiration cytology in clinically node-negative breast cancer patients who are at
      high risk for axillary metastasis. Following institutional review board approval
      and Health Insurance Portability and Accountability Act (HIPAA) compliance,
      sonographic axillary surveys from 112 patients considered at high risk for
      axillary metastases were reviewed retrospectively for the following abnormal
      features: asymmetric cortical thickening/lobulations; loss or compression of the
      hyperechoic medullary region; absence of fatty hilum; abnormal lymph node shape;
      hypoechoic cortex; admixture of normal and abnormal appearing nodes; and
      increased peripheral blood flow. Patients with either normal or abnormal
      ultrasound exams, but negative cytology, underwent sentinel node mapping.
      Patients with abnormal ultrasound and positive cytology proceeded to complete
      axillary dissection. The number of positive nodes, the size of tumour deposits
      and the histological pattern of metastatic disease on the positive nodes were
      then correlated and compared with their corresponding sonographic abnormalities.
      Abnormalities related to the lymph node cortex were indicative of N1a disease.
      Features such as loss or compression of the hyperechoic medullary region, absence
      of fatty hilum, abnormal lymph node shape and increased peripheral blood flow
      were predictors of N2-3 disease. In conclusion, nodal sonographic characteristics
      of patients at high risk for metastases are useful predictors of tumour burden in
      the axilla. When combined with the results from aspiration cytology, these
      findings could modify the surgical approach to the axilla, eliminating the need
      for sentinel node mapping in a significant proportion of patients.

PMID- 18628333
TI  - Estimation of lumbar spine bone mineral density by dual-energy X-ray
      absorptiometry: standard anteroposterior scans vs sub-regional analyses of whole
      body scans.
AB  - Dual-energy X-ray absorptiometry of the lumbar spine (anteroposterior (AP) L(1)
      L(4) DXA) is one of the standards for testing bone density (BMD). Whole-body (WB)
      DXA scanning allows analysis of the L-spine (WB-LS). The objective of this study
      was (i) to predict the AP L(1)-L(4) BMD from the WB-LS BMD, and (ii) to compare
      WB and AP L(1)-L(4) T-scores. 132 women participated in the study (age, 50.84+/
      9.69 years; range, 21-74 years). AP L(1)-L(4) BMD was measured on a Hologic QDR
      4500-A densitometer, and was followed by a WB scan. Linear regression analyses
      and curve estimations were performed for area, bone mineral content (BMC), BMD
      and T-scores. Precision errors for BMD from AP scans and WB-LS scans were 1.37%
      and 1.65%, respectively. The best linear correlations were found for BMD,
      followed by the T-scores (R = 0.882 and 0.871; p<0.001). A power model for BMC
      (R(2) = 0.630) and a model S for BMD and the scanned area (R(2) = 0.841 and
      0.539) were built. Discordant classification between AP L(1)-L(4) and WB T-scores
      was found in 12.73% and 19.09% cases, respectively. WB T-score cut-off values of 
      2.35 and -0.90 produced the best sensitivity-to-specificity ratio in the
      diagnosis of lumbar spine osteoporosis and low bone mass. In conclusion, WB-LS
      analysis may provide data for the indirect estimation of spinal BMD.

PMID- 18628334
TI  - Factors predicting tumour regression in locally advanced cervical adenocarcinoma
      treated with balloon-occluded intra-arterial chemotherapy.
AB  - We retrospectively assessed the factors that may impede tumour reduction of
      locally advanced cervical adenocarcinoma treated with balloon-occluded arterial
      infusion chemotherapy (BOAI) as initial therapy. We reviewed the medical records
      and MRI scans of 31 patients (mean age, 54.7 years; age range, 33-78 years). BOAI
      was performed via uterine arteries in 21 patients, and via the anterior division
      or main trunk of the internal iliac artery (when the uterine arteries were
      obscured) in 10 patients. Tumour reduction rate was calculated from the tumour
      size on MRI before and after BOAI, and patients given chemotherapy were
      classified as "non-responders" or "responders". Factors including the patient's
      age, tumour stage (using the International Federation of Gynecology and
      Obstetrics classification), the artery used for infusion, infused drug, presence
      of intravenous systemic chemotherapy, initial tumour size, tumour volume and
      presence of lymph node metastases were assessed for their ability to predict
      tumour response to BOAI using univariate and multivariate analyses. Patients who
      underwent chemotherapy included 10 non-responders and 21 responders. The age of
      non-responders was significantly higher than that of responders (66 years vs 49
      years, p<0.001). Internal iliac arterial infusion significantly correlated with
      "no response" compared with uterine arterial infusion (p<0.001). In multivariate
      analyses, internal iliac arterial infusion was an independent predictor for BOAI
      non-responders (odds ratio, 19.6; 95% confidence interval, 1.4-280.6; p = 0.02).
      These data suggest that uterine arteries being obscured to arterial infusion may
      be associated with a poor response to BOAI for cervical adenocarcinoma.

PMID- 18628335
TI  - Wide spectrum of thoracic neurogenic tumours: a pictorial review of CT and
      pathological findings.
AB  - The purpose of this pictorial essay is to illustrate the radiological and
      pathological findings of a wide spectrum of neurogenic tumours of the thorax
      according to their anatomical location and histological subtype. Knowledge of
      these findings will narrow the differential diagnosis and provide guidance for
      patient management.

PMID- 18628336
TI  - The chest X-ray black hole.

PMID- 18628337
TI  - Muscle weakness correlates with muscle atrophy and precedes the development of
      inclusion body or rimmed vacuoles in the mouse model of DMRV/hIBM.
AB  - Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion
      body myopathy (hIBM), is characterized clinically by weakness and atrophy that
      initially involves the distal muscles and pathologically by the presence of
      rimmed vacuoles (RVs) or intracellular protein deposits in myofibers. It is
      caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N
      acetylmannosamine kinase (GNE) gene that is important in sialic acid synthesis.
      Recently, we generated a mouse model (Gne(-/-)hGNED176VTg) that exhibits muscle
      weakness and pathological changes similar to DMRV patients. To gain better
      understanding of the pathomechanism of DMRV, we determined temporal changes in
      the overall motor performance of this model mouse for DMRV in correlation with
      the structure and function of isolated skeletal muscles and muscle pathology.
      These DMRV mice exhibited muscle weakness, decreased whole muscle mass and cross
      sectional area (CSA), and reduced contractile power in an age-related manner.
      Single-fiber CSA further supported the finding of muscle atrophy that involved
      both type I and type II fibers. These results suggest that atrophy is highly
      correlated with reduced production of force at young age, both in vivo and ex
      vivo, thereby implicating the important role of atrophy in the pathomechanism of
      DMRV. In older age, and particularly in gastrocnemius muscles, RVs and
      intracellular inclusions were seen in type IIA fibers, further aggravating
      reduction of force and specific increase in twitch-tetanus ratio.

PMID- 18628338
TI  - Global expression profiling identifies a novel biosignature for protein
      aggregation R120GCryAB cardiomyopathy in mice.
AB  - Protein aggregation cardiomyopathy is a life-threatening manifestation of a
      multisystem disorder caused by the exchange mutation in the gene encoding the
      human small heat shock protein alphaB-crystallin (hR120GCryAB). Genetic studies
      in mice have established cardiac hR120GCryAB expression causes increased activity
      of glucose 6-phosphate dehydrogenase (G6PD) and "reductive stress" (Rajasekaran
      et al., Cell 130: 427-439, 2007). However, the initiating molecular events in the
      pathogenesis of this novel toxic gain-of-function mechanism remain poorly
      defined. In an integrated systems approach using gene expression profiling, we
      identified a "biosignature," whose features can be validated to predict the
      onset, rate of progression, and clinical outcome of R120GCryAB cardiomyopathy. At
      the 3 mo disease-related but compensated stage, we demonstrate that transcripts
      were only upregulated in three distinct pathways: stress response (e.g., Hsp70,
      Hsp90), glutathione metabolism (Gpx1, Gpx3, glutathione S-transferase), and
      complement and coagulation cascades in hR120GCryAB transgenic mouse hearts
      compared with either hCryAB WT transgenic mice or nontransgenic controls. In 6 mo
      old myopathic hearts, ribosomal synthesis and cellular remodeling associated with
      increased cardiac hypertrophy were additional upregulated pathways. In contrast,
      the predominant downregulated pathways were for oxidative phosphorylation, fatty
      acid metabolism, intermediate metabolism, and energetic balance, supporting their
      primary pathogenic roles by which G6PD-dependent reductive stress causes cardiac
      decompensation and overt heart failure in hR120GCryAB cardiomyopathy. This study
      extends and confirms our previous findings that reductive stress is a causal
      mechanism for hR120G CryAB cardiomyopathy and demonstrates that alteration in
      glutathione pathway gene expression is an early biosignature with utility for
      presymptomatic detection.

PMID- 18628339
TI  - Resistance to diet-induced obesity in mice with a single substituted chromosome.
AB  - Obesity and its comorbidities are taking an increasing toll on human health. Key
      pathways that were identified with single gene variants in humans and model
      organisms have led to improved understanding and treatment of rare cases of human
      obesity. However, similar progress remains elusive for the more common
      multifactorial cases of metabolic dysfunction and disease. A survey of mouse
      chromosome substitution strains (CSSs) provided insight into the complex genetic
      control of diet-induced obesity and related conditions. We now report a survey of
      60 traits related to obesity and metabolic syndrome in mice with a single
      substituted chromosome as well as selected traits measured in congenic strains
      derived from the substituted strain. We found that each strain that was resistant
      to diet-induced obesity had a distinct phenotype that uniquely modeled different
      combinations of traits related to metabolic disease. For example, the chromosome
      6 CSS remained insulin resistant in the absence of obesity, demonstrating an
      atypical relationship between body weight and insulin resistance. These results
      provide insights into the genetic control of constant components of this mouse
      model of diet-induced metabolic disease as well as phenotypes that vary depending
      on genetic background. A better understanding of these genotype-phenotype
      relationships may enable a more individualized diagnosis and treatment of obesity
      and the metabolic syndrome.

PMID- 18628340
TI  - Quantitative trait loci for impaired glucose tolerance in nondiabetic SM/J and
      A/J mice.
AB  - The SMXA-5 recombinant inbred strain, which was established from nondiabetic
      parental SM/J and A/J mice, develops diabetic phenotypes such as impaired glucose
      tolerance. The combination of diabetogenic genes in the SM/J and A/J genomes
      impairs glucose tolerance in SMXA-5 mice. Using (SM/J x SMXA-5)F2 mice fed a high
      fat diet, we previously detected a diabetogenic locus, T2dm2sa, on chromosome
      (Chr) 2. The A/J allele at this locus is diabetogenic. The SM.A-T2dm2sa congenic
      mouse, in which the Chr 2 region of A/J including T2dm2sa was introgressed into
      SM/J, showed obviously impaired glucose tolerance. These results indicate that
      SM.A-T2dm2sa mice develop diabetogenic traits due to T2dm2sa with the A/J allele
      and unknown diabetogenic loci with the SM/J allele. The aim of this study was to
      dissect these unknown loci, using quantitative trait locus (QTL) analysis in the
      (A/J x SM.A-T2dm2sa) F2 intercross fed a high-fat diet. The results revealed a
      highly significant QTL, T2dm4sa, for glucose tolerance on Chr 6 and a significant
      QTL, T2dm5sa, for glucose tolerance on Chr 11. These loci with the SM/J allele
      were diabetogenic. The diabetogenic effect of T2dm4sa or T2dm5sa was verified by
      the impairment of glucose tolerance in the A/J-6(SM) or A/J-11(SM) consomic
      strain, in which Chr 6 or Chr 11 of SM/J is introgressed into A/J, respectively.
      These results demonstrate that diabetogenic loci exist in the genomes of
      nondiabetic A/J and SM/J mice and suggest that T2dm2sa with the A/J allele and
      T2dm4sa and/or T2dm5sa with the SM/J allele elicit impaired glucose tolerance in
      SM.A-T2dm2sa mice.

PMID- 18628341
TI  - Occult carotid artery disease in patients who have undergone coronary
      angioplasty.
AB  - OBJECTIVES: The aim was to evaluate the prevalence of asymptomatic mild (30-49%),
      moderate (50-69%) and severe (70-99%) ICA stenosis in patients who underwent
      previous coronary angioplasty (PTA). METHODS: After obtaining ethics committee
      approval, 144 consecutive patients aged between 65 and 75 years were invited for
      carotid Duplex evaluation with a linear 6 MHz array transducer by trained
      vascular sonographers within a single unit. A peak systolic velocity >230 cm/s in
      the ICA was considered as significant (>70% stenosis). RESULTS: Of the 144
      patients approached, 117 (81%) attended (male:female ratio 3.2:1, age range 65-75
      years, median age 71 years). Duplex ultrasound revealed one occlusion, 70% or
      more ICA stenosis in three patients (2.6%), 50-69% stenosis in 12 patients
      (10.3%) and 30-49% stenosis in 29 patients (24.8%). CONCLUSIONS: Carotid artery
      disease with a luminal stenosis of 30% or more is common in patients who
      underwent previous PTA. The yield of significant ICA stenosis (70% or more),
      which would benefit from carotid endarterectomy according to the Asymptomatic
      Carotid Surgery Trial is low. Recommendation for initial screening and subsequent
      follow-up Duplex examination for evaluation of disease progression of such
      cohorts remains debatable.

PMID- 18628342
TI  - Early tracheal extubation in adults undergoing single-lung transplantation for
      chronic obstructive pulmonary disease: pilot evaluation of perioperative outcome.
AB  - The objective of this pilot study was to evaluate the safety and success of early
      tracheal extubation (ETE) as compared to delayed tracheal extubation (DTE) in
      single-lung transplantation (SLT) for chronic obstructive pulmonary disease
      (COPD). This retrospective observational study was undertaken at a university
      hospital. Fifty-seven adult patients who underwent SLT for COPD (1998-2003) were
      enrolled. The study cohort was divided into an ETE subgroup (tracheal extubation
      in the operating room) or a DTE subgroup (tracheal extubation in the intensive
      care unit). There were no significant differences in perioperative outcomes
      between subgroups (in-hospital mortality; length of stay; prolonged mechanical
      ventilation; primary graft dysfunction; pneumonia; atrial fibrillation; renal
      dysfunction; and, sepsis). The anesthetic technique associated with ETE in SLT
      for COPD was characterized by limited systemic anesthetics and perioperative
      thoracic epidural analgesia. Appropriate ETE in SLT for COPD is not only safe but
      also results in equivalent perioperative outcome when compared to the traditional
      technique of DTE. Future studies should be powered to examine whether ETE reduces
      native lung complications such as hyperinflation, pneumonia and pneumothorax.

PMID- 18628343
TI  - The changing spectrum of bioprostheses hydrodynamic performance: considerations
      on in-vitro tests.
AB  - The aims of the present study were to compare hydrodynamics of three pericardial
      and two porcine valves while performing at different stroke volume (SV) and
      increasing pulse rate (PR). Carpentier-Edwards Magna-21 (CEM), Sorin Soprano-20
      (SS), Mitroflow-23 (MF), SJM-Biocor-Epic-Supra-21 (SJME), and Medtronic Mosaic
      Ultra-23 (MMU) were tested in the aortic chamber (23-mm in diameter) of the
      Sheffield-Pulse-Duplicator. The tests were carried out at increasing pulse-rate
      and at each pulse-rate the valve was tested at different SV. CEM and MF showed
      significantly lower gradients than porcine valves and SS. Transvalvular gradients
      were unrelated to PR showing a constant value with increasing PR. While SJME
      valve showed the lowest regurgitant volume, on the contrary CEM showed the
      highest. At increasing SV, effective-orifice-area (EOA) observed with CEM was
      significantly larger than with the other tested valves, even though at SV 60 ml
      MF was comparable and at SV 65 ml significantly better. SS, SJME and MMU showed
      comparable EOAs with bigger area at increasing PR. The latter relation was
      reversed for CEM and MF. Our results show that CEM and MF have shown
      significantly better in-vitro hydrodynamics in comparison with their porcine
      counterpart and SS. Nevertheless, at increasing pulse rate, porcine tissue valves
      and SS may guarantee higher EOA values.

PMID- 18628344
TI  - Surgical treatment of atrial fibrillation using cryothermy in patients undergoing
      mitral valve surgery.
AB  - Surgical treatment of atrial fibrillation (AF) using a variety of energy sources
      and a mixture of lesion sets has become an important adjunct in patients
      undergoing cardiac surgery. We retrospectively analyzed prospectively collected
      data of 141 patients with a history of AF (mean duration of AF 35+/-39 months;
      intermittent AF: n=72; 51%; permanent AF: 69 (49%)) who underwent a left-sided
      Cryomaze procedure in conjunction with mitral valve (MV) surgery between January
      2003 and September 2006. Freedom from AF was 77% at discharge and 87% at a mean
      follow-up of 305+/-195 days with a decreasing rate of AF during the first 3-9
      months from 13% to 9% and an increase beyond the first year (29% at 2 years).
      Predictors of failed Cryomaze in multivariate analysis were left atrial size >50
      mm (OR=5.7), AF at surgery (OR=5.0) and cardiac reoperation (OR=3.4), whereas
      preoperative beta-blocker treatment was a predictor of success (OR=0.2). Our data
      suggest that a left-sided Cryomaze procedure effectively restores sinus rhythm in
      patients with AF undergoing MV surgery. The success rate should not be evaluated
      immediately postoperatively because there is a steady increase in the rate of
      patients with freedom from AF in the first year. It appears, however, that there
      is a higher rate of recurrence during later follow-up.

PMID- 18628346
TI  - Undescended testes in children: the paediatric urologist's point of view.
AB  - Undescended testes (UDT) are found in 1% boys at the age of 1-year old, 3% of
      full-term male infants and 33% in premature babies at birth. Spontaneous descent
      is possible until 6 months of age. The two main phases of descent of the testis
      during gestation are described, as well as the possible aetiologies, the
      consequences of an abnormal migration, and the main locations of UDTs. Clinical
      examination is essential and should be done in optimal conditions. Laparoscopic
      exploration is the only valuable complementary investigation in the case of non
      palpable UDT.

PMID- 18628345
TI  - Rituximab in relapsing Graves' disease, a phase II study.
AB  - OBJECTIVE: Conventional therapies for Graves' disease, consisting of medical
      therapy or radioiodine are unsatisfactory, because of limited efficacy and
      adverse events. Interventions aimed at the underlying autoimmune pathogenesis of
      Graves' disease may be worthwhile to explore. We therefore performed a
      prospective, 26-week phase II study with open-ended observational extension to
      assess the efficacy of rituximab in patients with recurrent Graves' disease.
      DESIGN: We performed a prospective, 26-week phase II study with open-ended
      observations. METHODS: Thirteen patients with relapsing Graves' disease (9
      females and 4 males, age 39.5+/-9.5 years) received 2 dosages of rituximab 1000
      mg i.v. with a 2-week interval. Before administration and on several periods
      after the administration of TSH, free thyroxine (FT(4)), thyrotropin binding
      inhibitory immunoglobulins (TBII) and the proportion of CD19 and MS4A1 positive
      peripheral blood mononuclear cells were measured. RESULTS: The proportion of
      MS4A1 positive lymphocytes decreased in all patients from 5.8% at baseline to
      1.4% at 26 weeks (P=0.007). Four patients with high initial FT(4) levels did not
      respond to treatment. All remaining patients had a decrease in FT(4) levels at 26
      weeks (P=0.001) and an increase in TSH levels (P=0.011). TBII decreased in all
      remaining patients (P=0.003). At a follow-up time of 14-27 months, nine of these
      patients were still euthyroid with normal FT(4) (P<0.001) and TSH levels
      (P=0.008). CONCLUSIONS: The present study results suggest a beneficial role of
      rituximab in mild relapsing Graves' disease. A subsequent randomized controlled
      trial with rituximab is recommended.

PMID- 18628347
TI  - Sexism, sex selection and 'family balancing'.

PMID- 18628348
TI  - The evolution of the cognitive model of depression and its neurobiological
      correlates.
AB  - Although the cognitive model of depression has evolved appreciably since its
      first formulation over 40 years ago, the potential interaction of genetic,
      neurochemical, and cognitive factors has only recently been demonstrated.
      Combining findings from behavioral genetics and cognitive neuroscience with the
      accumulated research on the cognitive model opens new opportunities for
      integrated research. Drawing on advances in cognitive, personality, and social
      psychology as well as clinical observations, expansions of the original cognitive
      model have incorporated in successive stages automatic thoughts, cognitive
      distortions, dysfunctional beliefs, and information-processing biases. The
      developmental model identified early traumatic experiences and the formation of
      dysfunctional beliefs as predisposing events and congruent stressors in later
      life as precipitating factors. It is now possible to sketch out possible genetic
      and neurochemical pathways that interact with or are parallel to cognitive
      variables. A hypersensitive amygdala is associated with both a genetic
      polymorphism and a pattern of negative cognitive biases and dysfunctional
      beliefs, all of which constitute risk factors for depression. Further, the
      combination of a hyperactive amygdala and hypoactive prefrontal regions is
      associated with diminished cognitive appraisal and the occurrence of depression.
      Genetic polymorphisms also are involved in the overreaction to the stress and the
      hypercortisolemia in the development of depression--probably mediated by
      cognitive distortions. I suggest that comprehensive study of the psychological as
      well as biological correlates of depression can provide a new understanding of
      this debilitating disorder.

PMID- 18628349
TI  - Very low birth weight and behavioral symptoms of attention deficit hyperactivity
      disorder in young adulthood: the Helsinki study of very-low-birth-weight adults.
AB  - OBJECTIVE: Children with very low birth weight (<1500 g) are at increased risk
      for attention deficit hyperactivity disorder (ADHD). Whether this increased risk
      continues into adulthood is unknown. The authors assessed behavioral symptoms of
      ADHD in a well-characterized cohort of very-low-birth-weight young adults who
      were either small for gestational age (less than two standard deviations below
      the Finnish mean) or appropriate for gestational age (within two standard
      deviations of the mean). METHOD: A total of 162 very-low-birth-weight subjects
      (small for gestational age: N=52; appropriate for gestational age: N=110) and 172
      term comparison subjects 18 to 27 years of age completed the Adult Problem
      Questionnaire, which yielded six exploratory factor analysis-derived subscales.
      Participants were also asked about substance use. RESULTS: Very-low-birth-weight
      adults in the small for gestational age subgroup scored higher on the executive
      dysfunctioning and emotional instability subscales of the Adult Problem
      Questionnaire than did those in the appropriate for gestational age subgroup and
      the comparison group. The appropriate for gestational age and comparison groups
      had similar scores on these subscales. On the alcohol use subscale of the Adult
      Problem Questionnaire, both the appropriate and small for gestational age
      subgroups scored lower than comparison subjects and also reported fewer risk
      taking behaviors (alcohol, smoking, and use of recreational drugs) than did
      comparison subjects. CONCLUSIONS: Rather than very low birth weight per se,
      intrauterine growth retardation, as reflected by small for gestational age status
      in the very-low-birth-weight subjects, confers a risk for behavioral and
      emotional adversity related to ADHD in young adulthood.

PMID- 18628350
TI  - A genome screen for quantitative trait loci influencing schizophrenia and
      neurocognitive phenotypes.
AB  - OBJECTIVE: Deficits in neurocognitive function have been demonstrated in
      individuals with schizophrenia and in the unaffected family members of these
      individuals. Genetic studies of such complementary traits, along with traditional
      analyses of diagnosis, may help to elucidate the biological pathways underlying
      familial liability to schizophrenia and related disorders. The authors conducted
      a multiplex, multigenerational family study using a genome-wide screen for
      schizophrenia and related neurocognitive phenotypes. METHOD: Participants were 1)
      676 European American individuals from 43 families, ascertained through an
      individual with schizophrenia, and 2) 236 healthy comparison subjects.
      Participants were evaluated clinically and examined through the use of a
      computerized neurocognitive test battery that provided measures of accuracy and
      speed on the cognitive domains of abstraction and mental flexibility; attention;
      verbal, face, and spatial memory; language and reasoning; spatial and emotion
      processing; and sensorimotor dexterity. A genome-wide linkage screen was also
      performed. Healthy comparison subjects were included in order to obtain normative
      phenotypic data but were not genotyped. RESULTS: Significant evidence for linkage
      of schizophrenia to chromosome 19q was observed. Analysis of cognitive traits
      revealed significant linkage to chromosome 5q for the domains of abstraction and
      mental flexibility. A variety of other neurocognitive traits also showed nominal
      evidence of linkage to the 5q region. Joint analyses with diagnosis suggested
      that this quantitative trait locus may also influence schizophrenia. CONCLUSIONS:
      Although chromosome 5 has been implicated in previous linkage studies of
      schizophrenia, the identification of the chromosome 19 quantitative trait locus
      is a novel finding. The identification of the chromosome 5 quantitative trait
      locus through linkage to neurocognitive phenotypes in the present study may
      inform functional hypotheses pertaining to how genotypes are connected to
      disease.

PMID- 18628351
TI  - Auxin regulates Arabidopsis anther dehiscence, pollen maturation, and filament
      elongation.
AB  - We provide evidence on the localization, synthesis, transport, and effects of
      auxin on the processes occurring late in Arabidopsis thaliana stamen development:
      anther dehiscence, pollen maturation, and preanthesis filament elongation.
      Expression of auxin-sensitive reporter constructs suggests that auxin effects
      begin in anthers between the end of meiosis and the bilocular stage in the
      somatic tissues involved in the first step of dehiscence as well as in the
      microspores and in the junction region between anther and filament. In situ
      hybridizations of the auxin biosynthetic genes YUC2 and YUC6 suggest that auxin
      is synthesized in anthers. In agreement with the timing of auxin effects, the
      TIR1, AFB1, AFB2, and AFB3 auxin receptor-encoding genes are transcribed in
      anthers only during late stages of development starting at the end of meiosis. We
      found that in tir1 afb triple and quadruple mutants, anther dehiscence and pollen
      maturation occur earlier than in the wild type, causing the release of mature
      pollen grains before the completion of filament elongation. We also assessed the
      contribution of auxin transport to late stamen developmental processes. Our
      results suggest that auxin synthesized in anthers plays a major role in
      coordinating anther dehiscence and pollen maturation, while auxin transport
      contributes to the independent regulation of preanthesis filament elongation.

PMID- 18628353
TI  - Insulin and muscle protein turnover in humans: stimulatory, permissive,
      inhibitory, or all of the above?

PMID- 18628352
TI  - Arabidopsis 10-formyl tetrahydrofolate deformylases are essential for
      photorespiration.
AB  - In prokaryotes, PurU (10-formyl tetrahydrofolate [THF] deformylase) metabolizes
      10-formyl THF to formate and THF for purine and Gly biosyntheses. The Arabidopsis
      thaliana genome contains two putative purU genes, At4g17360 and At5g47435.
      Knocking out these genes simultaneously results in plants that are smaller and
      paler than the wild type. These double knockout (dKO) mutant plants show a 70
      fold increase in Gly levels and accumulate elevated levels of 5- and 10-formyl
      THF. Embryo development in dKO mutants arrests between heart and early bent
      cotyledon stages. Mature seeds are shriveled, accumulate low amounts of lipids,
      and fail to germinate. However, the dKO mutant is only conditionally lethal and
      is rescued by growth under nonphotorespiratory conditions. In addition, culturing
      dKO siliques in the presence of sucrose restores normal embryo development and
      seed viability, suggesting that the seed and embryo development phenotypes are a
      result of a maternal effect. Our findings are consistent with the involvement of
      At4g17360 and At5g47435 proteins in photorespiration, which is to prevent
      excessive accumulation of 5-formyl THF, a potent inhibitor of the Gly
      decarboxylase/Ser hydroxymethyltransferase complex. Supporting this role,
      deletion of the At2g38660 gene that encodes the bifunctional 5,10-methylene THF
      dehydrogenase/5,10-methenyl THF cyclohydrolase that acts upstream of 5-formyl THF
      formation restored the wild-type phenotype in dKO plants.

PMID- 18628354
TI  - Short-term flexibility of myocardial triglycerides and diastolic function in
      patients with type 2 diabetes mellitus.
AB  - Short-term caloric restriction increases plasma levels of nonesterified fatty
      acids (NEFAs) and is associated with increased myocardial triglyceride (TG)
      content and decreased myocardial function in healthy subjects. Whether this
      flexibility of myocardial TG stores and myocardial function is also present in
      patients with type 2 diabetes mellitus (T2DM) is yet unknown. Myocardial TG
      content and left ventricular (LV) ratio between the early (E) and atrial (A)
      diastolic filling phase (E/A) were determined using magnetic resonance (MR)
      spectroscopy and MR imaging, respectively, before and after a 3-day very low
      calorie diet (VLCD) in 11 patients with T2DM. In addition, we studied patients
      after a 3-day VLCD combined with the antilipolytic drug acipimox. The VLCD
      induced myocardial TG accumulation [from 0.66 +/- 0.09% (mean +/- SE, baseline)
      to 0.98 +/- 0.16%, P = 0.028] and a decrease in E/A ratio [from 1.00 +/- 0.05
      (baseline) to 0.90 +/- 0.06, P = 0.002]. This was associated with increased
      plasma NEFA levels (from 0.57 +/- 0.08 mmol/l at baseline to 0.92 +/- 0.12, P =
      0.019). After the VLCD with acipimox, myocardial TG content, diastolic function,
      and plasma NEFA levels were similar to baseline values. In conclusion, in
      patients with T2DM, a VLCD increases myocardial TG content and is associated with
      a decrease in LV diastolic function. These effects were not observed when a VLCD
      was combined with acipimox, illustrating the physiological flexibility of
      myocardial TG stores and myocardial function in patients with T2DM.

PMID- 18628356
TI  - Molecular analysis of multifocal papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma (PTC) frequently presents as a multifocal process. To
      study the importance of separating independent primary (IP) from intrathyroid
      metastatic (ITM) PTC, we examined 19 molecular markers on 42 separate tumors from
      18 multifocal PTC cases. In 12 of 18 (66.7%) cases, including 6 of 12 (50%)
      papillary microcarcinoma cases, the same or similar profile of loss of
      heterozygosities (LOH) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF)
      mutation was demonstrated, indicating that they were from the same primary and
      represented ITM. Different profiles of LOHs and BRAF mutation were detected in
      separate tumors of 6 of 18 cases, indicating that they represented IP. Patients
      with ITM, including papillary microcarcinoma, had significantly increased lymph
      node metastasis. The frequencies of LOHs of 17q21, 17p13, 10q23, and 22q13 were
      higher in tumors with lymph node metastasis, suggesting that these LOHs may be
      important in increased lymph node metastasis. LOH of 9p21 was found at the
      highest frequency in PTC (53.8%), followed by 1p36 (46.2%), 10q23 (34.6%), and
      22q13 (34.6%). Papillary microcarcinoma had acquired similar genomic mutations as
      conventional PTC, but higher frequencies of mutations of BRAF, 1p36, 18q, and
      22q13 were found in the larger PTC, suggesting that they might play a role in the
      aggressiveness of PTC. Different profiles of mutations were observed in
      conventional, follicular variants, and diffuse sclerosing variant of PTC, which
      might influence the different morphological appearances and clinical courses. In
      conclusion, molecular analysis can separate multifocal IP PTC from ITM PTC, and
      may be more important than tumor size in predicting lymph node metastasis,
      aggressiveness, and prognosis of PTC.

PMID- 18628355
TI  - Adiponectin deficiency promotes endothelial activation and profoundly exacerbates
      sepsis-related mortality.
AB  - Sepsis is a multifactorial, and often fatal, disorder typically characterized by
      widespread inflammation and immune activation with resultant endothelial
      activation. In the present study, we postulated that the adipokine adiponectin
      serves as a critical modulator of survival and endothelial activation in sepsis.
      To this aim, we evaluated both loss-of-function (adiponectin gene-deficient mice)
      and subsequent gain-of-function (recombinant adiponectin reconstitution)
      strategies in two well-established inflammatory models, cecal ligation
      perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq(-/-) mice,
      subjected to CLP, exhibited a profound ( approximately 8-fold) reduction in
      survival compared with their wild-type Adipoq(+/+) littermates after 48 h.
      Furthermore, compared with wild-type controls, thioglycollate challenge resulted
      in a markedly greater influx of peritoneal neutrophils in Adipoq(-/-) mice
      accompanied by an excess production of key chemoattractant cytokines (IL-12p70,
      TNFalpha, MCP-1, and IL-6) and upregulation of aortic endothelial adhesion
      molecule VCAM-1 and ICAM-1 expressions. Importantly, all of these effects were
      blunted by recombinant total adiponectin administration given 3 days prior to
      thioglycollate challenge. The protective effects of adiponectin were ascribed
      largely to higher-order adiponectin oligomers, since administration of
      recombinant C39A trimeric adiponectin did not attenuate endothelial adhesion
      molecule expression in thioglycollate-challenged Adipoq(-/-) mice. These data
      suggest a critical role of adiponectin as a modulator of survival and endothelial
      inflammation in experimental sepsis and a potential mechanistic link between
      adiposity and increased sepsis.

PMID- 18628357
TI  - Changes in plasma arginine vasopressin concentrations in cyclists participating
      in a 109-km cycle race.
AB  - OBJECTIVE: To evaluate the osmotic and non-osmotic regulation of arginine
      vasopressin (AVP) during endurance cycling. DESIGN: Observational study. Setting
      109 km cycle race. PARTICIPANTS: 33 Cyclists. INTERVENTIONS: None. MAIN OUTCOME
      MEASUREMENTS: Plasma sodium concentration ([Na(+)]), plasma volume (PV) and
      plasma arginine vasopressin (AVP) concentration ([AVP](p)). RESULTS: A fourfold
      increase in [AVP](p) occurred despite a 2-mmol l(-1) decrease in plasma [Na(+)]
      combined with only modest (5%) PV contraction. A significant inverse correlation
      was noted between [AVP](p) Delta and urine osmolality Delta (r = -0.41, p<0.05),
      whereas non-significant inverse correlations were noted between [AVP](p) and both
      plasma [Na(+)] Delta and % PV Delta. Four cyclists finished the race with
      asymptomatic hyponatraemia. The only significant difference between the entire
      cohort with this subset of athletes was postrace plasma [Na(+)] (137.7 vs 133.5
      mmol l(-1), p<0.001) and plasma [Na(+)] Delta (-1.9 vs -5.1 mmol l(-1), p<0.05).
      The mean prerace [AVP](p) of these four cyclists was just below the minimum
      detectable limit (0.3 pg ml(-1)) and increased marginally (0.4 pg ml(-1)) despite
      the decline in plasma [Na(+)]. CONCLUSIONS: The osmotic regulation of [AVP](p)
      during competitive cycling was overshadowed by non-osmotic AVP secretion. The
      modest decrease in PV was not the primary non-osmotic stimulus to AVP. Partial
      suppression of AVP occurred in four (12%) cyclists who developed hyponatraemia
      during 5 h of riding. Therefore, these results confirm that non-osmotic AVP
      secretion and exercise-associated hyponatraemia does, in fact, occur in cyclists
      participating in a 109 km cycle race. However, the stimuli to AVP is likely
      different between cycling and running.

PMID- 18628358
TI  - Validity of physical activity monitors in adults participating in free-living
      activities.
AB  - BACKGROUND: For a given subject, time in moderate to very vigorous intensity
      physical activity (MVPA) varies substantially among physical activity monitors.
      OBJECTIVE: In the present study, the primary objective, whether time in MVPA
      recorded with SenseWear Pro(2) Armband (Armband; BodyMedia, Pittsburgh,
      Pennsylvania, USA), ActiGraph (7164, LLC, Fort Walton Beach, Florida, USA), ikcal
      (Teltronic AG, Biberist, Switzerland) and ActiReg (PreMed AS, Oslo, Norway) is
      different compared with indirect calorimetry, was determined. The secondary
      objective, whether these activity monitors estimate energy expenditure
      differently compared with indirect calorimetry, was also determined. MATERIAL AND
      METHODS: The activity monitors and a portable oxygen analyser were worn by 14 men
      and 6 women for 120 min doing a variety of activities of different intensities.
      Resting metabolic rate was measured with indirect calorimetry. The cutoff points
      defining moderate, vigorous and very vigorous intensity were three, six and nine
      times resting metabolic rate. RESULTS: Time in MVPA was overestimated by 2.9% and
      2.5% by Armband and ActiGraph, respectively, and was underestimated by 11.6% and
      98.7% by ikcal and ActiReg, respectively. ActiReg (p = 0.004) and ActiGraph (p =
      0.007) underestimated energy expenditure in MVPA, and all monitors underestimated
      total energy expenditure (by 5% to 21%). CONCLUSIONS: Recorded time in MVPA and
      energy expenditure varies substantially among physical activity monitors. Thus,
      when comparing physical activity level among studies, it is essential to know the
      type of physical activity monitor being used.

PMID- 18628359
TI  - General practitioners' perceptions and practices of physical activity
      counselling: changes over the past 10 years.
AB  - OBJECTIVE: In this work, trends in general practitioners' (GP) knowledge,
      confidence and practices in promoting physical activity to patients over a 10
      year period (1997-2007) were studied. DESIGN: Repeated cross-sectional population
      survey SETTING: General practice in New South Wales (Australia) PARTICIPANTS: 646
      (40%), 747 (53%) and 511 (64%) GPs that were registered in a selection of urban
      and rural divisions in New South Wales participated in 2007, 2000 and 1997,
      respectively. MAIN OUTCOME MEASURES: Self-report questionnaire on the GP's
      knowledge, confidence, role perception, attendance of continuous professional
      development and counselling practice with regard to promoting physical activity
      in their patients were the main outcome measures. RESULTS: The majority of GPs
      felt confident in giving physical activity advice and saw it as their role to do
      so. The proportion of GPs with high confidence and role perception increased
      between 1997 and 2000 (p<0.001) but remained unchanged thereafter. In 1997, GPs
      were 0.54 times less likely (95% CI 0.42 to 0.69, p<0.001) to discuss physical
      activity with more than 10 patients per week than GPs in 2007. However, the
      percentage of new patients that were asked about their physical activity did not
      change over the last decade. CONCLUSIONS: Most increases in the proportion of GPs
      reporting high knowledge, role perception and confidence in giving physical
      activity advice to patients occurred between 1997 and 2000 and remained unchanged
      thereafter. In 2007, GPs appeared to give more physical activity advice, but
      Australian general practice is not yet living up to its potential with regard to
      physical activity promotion.

PMID- 18628360
TI  - Elevation of systemic matrix metalloproteinases 2 and 7 and tissue inhibitor of
      metalloproteinase 2 in patients with a history of Achilles tendon rupture: pilot
      study.
AB  - OBJECTIVES: In this study, serum levels of matrix metalloproteinases (MMPs) and
      tissue inhibitors of metalloproteinases (TIMPs) between patients with a history
      of Achilles tendon rupture and blood donor controls were compared, and their
      relation to mechanical properties of the tendons during healing were studied.
      METHODS: More than 3 years after injury, serum levels of MMP-1, MMP-2, MMP-3, MMP
      7, MMP-8, MMP-9 and MMP-13, TIMP-1 and TIMP-2 in eight patients who had Achilles
      tendon rupture were measured. Twelve blood donors served as controls. During the
      early phase of healing, the tendon modulus of elasticity was calculated from
      radiostereometric data and tendon cross-sectional area. RESULTS: Patients with a
      history of Achilles tendon rupture had increased levels of MMP-2 (median
      difference 10%, p=0.01), MMP-7 (median difference 15%, p=0.02) and TIMP-2 (median
      difference 36%, p=0.02), compared with controls. Levels of MMP-7, measured 3
      years after injury, correlated inversely to tendon modulus of elasticity
      (r(s)=20.83, p=0.02) and positively to tendon elongation (r(s)=0.74, p=0.05)
      during the early phase of healing. There was a trend towards positive correlation
      between MMP-7 and cross-sectional area during the early phase of healing
      (r(s)=0.67, p=0.08). CONCLUSIONS: Patients with a history of Achilles tendon
      rupture appear to have elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In
      these pilot data, the view that the MMP-TIMP system is involved in tendinopathy
      is supported and that disturbances in proteolytic control might be generalised
      are suggested.

PMID- 18628362
TI  - Regulation of endocrine and paracrine sources of Igfs and Gh receptor during
      compensatory growth in hybrid striped bass (Morone chrysops X Morone saxatilis).
AB  - Compensatory growth (CG) is a period of growth acceleration that exceeds normal
      rates after animals are alleviated of certain growth-stunting conditions. In
      hybrid striped bass (HSB, Morone chrysops X Morone saxatilis), 3 weeks of
      complete feed restriction results in a catabolic state that, when relieved,
      renders a subsequent phase of CG. The catabolic state was characterized by
      depressed levels of hepatic Type I and II GH receptor (ghr1, ghr2) and igf1 mRNA,
      along with considerable decreases in plasma Igf1. The state of catabolism also
      resulted in significant declines in hepatic igf2 mRNA and in circulating 40 kDa
      Igf-binding protein (Igfbp). Skeletal muscle expression of ghr2 mRNA was
      significantly increased. Upon realimentation, specific growth rates (SGRs) were
      significantly higher than sized-matched controls, indicating a period of CG.
      Hepatic ghr1, ghr2, igf1 and igf2 mRNA levels along with plasma Igf1 and 40 kDa
      Igfbp increased rapidly during realimentation. Plasma Igf1 and total hepatic igf2
      mRNA were significantly correlated to SGR throughout the study. Skeletal muscle
      igf1 mRNA also increased tenfold during CG. These data suggest that endocrine and
      paracrine/autocrine components of the GH-Igf axis, namely igf1, igf2, and ghr1
      and ghr2, may be involved in CG responses in HSB, with several of the gene
      expression variables exceeding normal levels during CG. We also demonstrate that
      normalization of hepatic mRNA as a function of total liver production, rather
      than as a fraction of total RNA, may be a more biologically appropriate method of
      quantifying hepatic gene expression when using real-time PCR.

PMID- 18628361
TI  - Initiating and maintaining resistance training in older adults: a social
      cognitive theory-based approach.
AB  - Numerous research studies performed in "lab-gyms" with supervised training have
      demonstrated that simple, brief (20-30 min) resistance training protocols
      performed 2-3/week following the American College of Sports Medicine's guidelines
      positively affect risk factors associated with heart disease, cancers, diabetes,
      sarcopenia and other disabilities. For more than a decade, resistance training
      has been recommended for adults, particularly older adults, as a prime preventive
      intervention, and increasing the prevalence of resistance training is an
      objective of Healthy People 2010. However, the prevalence rate for resistance
      training is only estimated at 10-15% for older adults, despite the leisure time
      of older adults and access to facilities in developed countries. The reasons that
      the prevalence rate remains low include public health policy not emphasising
      resistance training, misinformation, and the lack of theoretically driven
      approaches demonstrating effective transfer and maintenance of training to
      minimally supervised settings once initial, generally successful, supervised
      training is completed. Social cognitive theory (SCT) has been applied to physical
      activity and aerobic training with some success, but there are aspects of
      resistance training that are unique including its intensity, progression,
      precision, and time and place specificity. Social cognitive theory, particularly
      with a focus on self-regulation and response expectancy and affect within an
      ecological context, can be directly applied to these unique aspects of resistance
      training for long-term maintenance.

PMID- 18628363
TI  - A comparison of social skills profiles in intellectually disabled adults with and
      without ASD.
AB  - The purpose of this study was to systematically examine the social-skills
      profiles among adults with autism spectrum disorders (ASD) and intellectual
      disability (ID). Using one-way multivariate analysis of variance (MANOVA), three
      groups (autism, pervasive developmental disorder-not otherwise specified [PDD
      NOS], and ID only) were compared on seven global measures of social behavior.
      There were 72 individuals in each group matched on level of ID, verbal ability,
      age, and gender. Distinctions were noted in the areas of positive social
      behaviors and negative nonverbal social behaviors. Those with autism displayed
      the greatest deficits in these areas, followed by those with PDD-NOS. The results
      support the notions that social impairment remains a distinct feature of ASD in
      adults with ID, that autism and PDD-NOS are two conditions on the same spectrum,
      and that this spectrum is relevant for adults with ID. Implications of the
      results and directions for future research are discussed.

PMID- 18628365
TI  - Warm, fuzzy feeling.

PMID- 18628366
TI  - Incidence, prevalence and mortality trends of dialysis end-stage renal disease in
      Taiwan from 1990 to 2001: the impact of national health insurance.
AB  - BACKGROUND: Incident and prevalent (I&P) rates in dialysis end-stage renal
      disease (ESRD) patients in Taiwan increased rapidly following the launch of
      National Health Insurance (NHI) in 1995. Our aim was to explore the impact of NHI
      on the status and trends of ESRD epidemiology in Taiwan. METHODS: This study was
      conducted using retrospective cohort analysis of data collected from the Taiwan
      national dialysis registry. RESULTS: From 1990 to 2001, I&P rates of ESRD
      patients increased 2.6 times from 126 to 331 per million populations (pmp) and
      3.46 times from 382 to 1322 pmp, respectively. Increasing ESRD was seen in
      patients who were middle-aged, elderly and who had diabetic nephropathy as their
      primary renal disease. The mean age of I&P patients increased by 7.2 years and
      7.1 years, respectively. All of these parameters increased markedly in 1995, the
      year of NHI implementation. First-year mortality decreased to 7.8 per 1000
      patient-months in 1994, and then increased to 18.0 in 2001. The cumulative
      survival rate of the elderly subgroup (age >65) in the incident 1990-1994 cohort
      was greater than in the 1995-1999 cohort. These data indicated that NHI
      implementation significantly influenced the inflow and the mortality of ESRD
      patients. CONCLUSION: In addition to presenting ESRD epidemiology in Taiwan, this
      study demonstrated that NHI implementation stimulated the growth of treated ESRD
      populations. Preventive plans mounted against chronic kidney diseases will be
      essential to reduce the growth of ESRD patient numbers and consequent economic
      burdens.

PMID- 18628367
TI  - Statin use is associated with early recovery of kidney injury after vascular
      surgery and improved long-term outcome.
AB  - BACKGROUND: Acute kidney injury (AKI) after major vascular surgery is an
      important risk factor for adverse long-term outcomes. The pleiotropic effects of
      statins may reduce kidney injury caused by perioperative episodes of hypotension
      and/or suprarenal clamping and improve long-term outcomes. METHODS: Of 2170
      consecutive patients undergoing lower extremity bypass or abdominal aortic
      surgery from 1995 to 2006, cardiac risk factors and medication were noted. A
      total of 515/1944 (27%) patients were statin users. Creatinine clearance (CrCl)
      was assessed preoperatively at 1, 2 and 3 days after surgery. Outcome measures
      were postoperative AKI and long-term mortality. Postoperative kidney injury was
      defined as a >10% decrease in CrCl on Day 1 or 2, compared to the baseline.
      Recovery of kidney function was defined as a CrCl >90% of the baseline value at
      Day 3 after surgery. Multivariable Cox regression analysis, including baseline
      cardiovascular risk factors, baseline CrCl and propensity score for statin use,
      was applied to evaluate the influence of statins on early postoperative kidney
      injury and long-term survival. RESULTS: AKI occurred in 664 (34%) patients
      [median -25% CrCl, range (-10% to -71%)]. Of these 664 patients, 313 (47%) had a
      complete recovery of kidney function at Day 3 after surgery. Age, hypertension,
      suprarenal cross-clamping and baseline CrCl predicted the development of kidney
      injury during the postoperative period. The incidence of kidney injury was
      similar among statin users and non-users (29% versus 25%, OR 1.15, 95% CI 0.9
      1.5). However, if kidney function deteriorated, statin use was associated with
      increased odds of complete kidney function recovery (OR 2.0, 95% CI 1.0-3.8).
      During a mean follow-up of 6.24 years, half of the patients died (55%).
      Importantly, statin use was also associated with an improved long-term survival,
      irrespective of kidney function change (HR 0.60, 95% CI 0.48-0.75). CONCLUSION:
      Statin use is associated with improved recovery from AKI after major surgery and
      has a beneficial effect on long-term survival.

PMID- 18628368
TI  - Dysphagia and an oesophageal stricture; not always cancer.

PMID- 18628369
TI  - Dissecting out the genetic origins of Barrett's oesophagus.

PMID- 18628370
TI  - Serine proteases: new players in diarrhoea-predominant irritable bowel syndrome.

PMID- 18628371
TI  - Pancreatitis: the neglected duct.

PMID- 18628372
TI  - A rare cause of "cellulitis".

PMID- 18628373
TI  - Management of lower gastrointestinal bleeding with haemodynamic instability.

PMID- 18628374
TI  - Occult gastro-intestinal cause of spastic paresis of the legs.

PMID- 18628375
TI  - Nautilus-patterned small intestines.

PMID- 18628376
TI  - A 'sticky' reason for chronic abdominal pain.

PMID- 18628377
TI  - Pathogenetic mechanisms of hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) in liver cirrhosis is a clinical manifestation of a
      low-grade cerebral oedema, which is exacerbated in response to ammonia and other
      precipitating factors. This low-grade cerebral oedema is accompanied by an
      increased production of reactive oxygen and nitrogen oxide species (ROS/RNOS),
      which trigger multiple protein and RNA modifications, thereby affecting brain
      function. The action of ammonia, inflammatory cytokines, benzodiazepines and
      hyponatraemia integrates at the level of astrocyte swelling and oxidative stress.
      This explains why heterogenous clinical conditions can precipitate HE episodes.
      Oxidised RNA species, which are formed in response to oxidative stress, also
      participate in local postsynaptic protein synthesis in neurons, which is required
      for memory formation. Although the functional consequences of RNA oxidation in
      this context remain to be established, these findings bear a potential
      biochemical explanation for the multiple alterations of neurotransmitter receptor
      systems and of synaptic plasticity. Such changes may in part also underlie the
      pathologically altered oscillatory networks in the brain of HE patients in vivo,
      as detected by magnetencephalography. These disturbances of oscillatory networks,
      which in part are triggered by hypothalamic structures, can explain the motor and
      cognitive deficits in patients with HE. Current therapeutic strategies aim at the
      elimination of precipitating factors. The potential of therapies targeting
      downstream pathophysiological events in HE has not yet been explored, but offers
      novel potential sites of therapeutic intervention.

PMID- 18628378
TI  - Asia Pacific consensus recommendations for colorectal cancer screening.
AB  - Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines
      are lacking. Through reviewing the literature and regional data, and using the
      modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and
      international experts launch consensus recommendations aiming to improve the
      awareness of healthcare providers of the changing epidemiology and screening
      tests available. The incidence, anatomical distribution and mortality of CRC
      among Asian populations are not different compared with Western countries. There
      is a trend of proximal migration of colonic polyps. Flat or depressed lesions are
      not uncommon. Screening for CRC should be started at the age of 50 years. Male
      gender, smoking, obesity and family history are risk factors for colorectal
      neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical
      tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening.
      Double-contrast barium enema and CT colonography are not preferred. In resource
      limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in
      diameter should be removed endoscopically and, following a negative colonoscopy,
      a repeat examination should be performed in 10 years. Screening for CRC should be
      a national health priority in most Asian countries. Studies on barriers to CRC
      screening, education for the public and engagement of primary care physicians
      should be undertaken. There is no consensus on whether nurses should be trained
      to perform endoscopic procedures for screening of colorectal neoplasia.

PMID- 18628380
TI  - "A brownish depressed area": a novel narrow band imaging colonoscopic finding of
      a depressed adenoma.

PMID- 18628381
TI  - Does Helicobacter pylori protect against asthma and allergy?

PMID- 18628382
TI  - Sequential treatment for Helicobacter pylori eradication in children.

PMID- 18628383
TI  - Nitazoxanide for cryptosporidial infection in Crohn's disease.

PMID- 18628385
TI  - TIPS with a polytetrafluoroethylene-lined stent graft and associated haemolytic
      anaemia.

PMID- 18628387
TI  - Bacterial translocation and cardiovascular complications of cirrhosis.

PMID- 18628388
TI  - Helminths as governors of inflammatory bowel disease.

PMID- 18628389
TI  - Clostridium difficile infection and inflammatory bowel disease: a marker for
      disease extent?

PMID- 18628391
TI  - Serotonin and insulin signaling team up to control growth in Drosophila.
AB  - Neuroendocrine signaling pathways play a central role in modulating animal body
      size in response to environmental signals. Little is known, however, regarding
      how these neuroendocrine circuits are controlled. An important advance in this
      area is reported in this issue of Genes & Development by Kaplan and colleagues
      (pp. 1877-1893), who show that serotonergic neurons regulate the growth of
      peripheral tissues in Drosophila through the insulin/IGF pathway.

PMID- 18628392
TI  - The intestinal stem cell.
AB  - The epithelium of the adult mammalian intestine is in a constant dialog with its
      underlying mesenchyme to direct progenitor proliferation, lineage commitment,
      terminal differentiation, and, ultimately, cell death. The epithelium is shaped
      into spatially distinct compartments that are dedicated to each of these events.
      While the intestinal epithelium represents the most vigorously renewing adult
      tissue in mammals, the stem cells that fuel this self-renewal process have been
      identified only recently. The unique epithelial anatomy makes the intestinal
      crypt one of the most accessible models for the study of adult stem cell biology.
      This review attempts to provide a comprehensive overview of four decades of
      research on crypt stem cells.

PMID- 18628393
TI  - Control of differentiation in a self-renewing mammalian tissue by the histone
      demethylase JMJD3.
AB  - The recent discovery of H3K27me3 demethylases suggests that H3K27me3 may
      dynamically regulate gene expression, but this potential role in mammalian tissue
      homeostasis remains uncharacterized. In the epidermis, a tissue that balances
      stem cell self-renewal with differentiation, H3K27me3, occupies the promoters of
      many differentiation genes. During calcium-induced differentiation, H3K27me3 was
      erased at these promoters in concert with loss of PcG protein occupancy and
      increased binding by the H3K27me3 demethylase, JMJD3. Within epidermal tissue,
      JMJD3 depletion blocked differentiation, while active JMJD3 dominantly induced
      it. These results indicate that epigenetic derepression by JMJD3 controls
      mammalian epidermal differentiation.

PMID- 18628394
TI  - Liver receptor homolog 1 is essential for ovulation.
AB  - Female fertility requires normal ovarian follicular growth and ovulation. The
      nuclear receptor liver receptor homolog 1 has been implicated in processes as
      diverse as bile acid metabolism, steroidogenesis, and cell proliferation. In the
      ovary, Lrh1 is expressed exclusively in granulosa and luteal cells. Using somatic
      targeted mutagenesis, we show that mice lacking Lrh1 in granulosa cells are
      sterile, due to anovulation. The preovulatory stimulus fails to elicit cumulus
      expansion, luteinization, and follicular rupture in these mice. Multiple defects,
      including severely reduced transactivation of the Lrh1 target gene, nitric oxide
      synthase 3, leads to increased intrafollicular estradiol levels in the absence of
      Lrh1. This further causes dysfunction of prostaglandin and hyaluronic acid
      cascades and interrupts cumulus expansion. Lack of Lrh1 also interferes with
      progesterone synthesis because of failure of normal expression of the Lrh1
      targets, steroidogenic acute regulatory protein and cytochrome P450 side-chain
      cleavage. In addition, expression of extracellular matrix proteases essential for
      ovulation is compromised. These results demonstrate that Lrh1 is a regulator of
      multiple mechanisms essential for maturation of ovarian follicles and for
      ovulation. Lrh1 is therefore a key modulator of female fertility and a potential
      target for contraception.

PMID- 18628395
TI  - A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate
      insulin signaling and control body size.
AB  - Growth and body size are regulated by the CNS, integrating the genetic
      developmental program with assessments of an animal's current energy state and
      environmental conditions. CNS decisions are transmitted to all cells of the
      animal by insulin/insulin-like signals. The molecular biology of the CNS growth
      control system has remained, for the most part, elusive. Here we identify NS3, a
      Drosophila nucleostemin family GTPase, as a powerful regulator of body size. ns3
      mutants reach <60% of normal size and have fewer and smaller cells, but exhibit
      normal body proportions. NS3 does not act cell-autonomously, but instead acts at
      a distance to control growth. Rescue experiments were performed by expressing
      wild-type ns3 in many different cells of ns3 mutants. Restoring NS3 to only 106
      serotonergic neurons rescued global growth defects. These neurons are closely
      apposed with those of insulin-producing neurons, suggesting possible
      communication between the two neuronal systems. In the brains of ns3 mutants,
      excess serotonin and insulin accumulate, while peripheral insulin pathway
      activation is low. Peripheral insulin pathway activation rescues the growth
      defects of ns3 mutants. The findings suggest that NS3 acts in serotonergic
      neurons to regulate insulin signaling and thus exert global growth control.

PMID- 18628396
TI  - Cdc7-Drf1 kinase links chromosome cohesion to the initiation of DNA replication
      in Xenopus egg extracts.
AB  - To establish functional cohesion between replicated sister chromatids, cohesin is
      recruited to chromatin before S phase. Cohesin is loaded onto chromosomes in the
      G1 phase by the Scc2-Scc4 complex, but little is known about how Scc2-Scc4 itself
      is recruited to chromatin. Using Xenopus egg extracts as a vertebrate model
      system, we showed previously that the chromatin association of Scc2 and cohesin
      is dependent on the prior establishment of prereplication complexes (pre-RCs) at
      origins of replication. Here, we report that Scc2-Scc4 exists in a stable complex
      with the Cdc7-Drf1 protein kinase (DDK), which is known to bind pre-RCs and
      activate them for DNA replication. Immunodepletion of DDK from Xenopus egg
      extracts impairs chromatin association of Scc2-Scc4, a defect that is reversed by
      wild-type, but not catalytically inactive DDK. A complex of Scc4 and the N
      terminus of Scc2 is sufficient for chromatin loading of Scc2-Scc4, but not for
      cohesin recruitment. These results show that DDK is required to tether Scc2-Scc4
      to pre-RCs, and they underscore the intimate link between early steps in DNA
      replication and cohesion.

PMID- 18628397
TI  - Rad53 regulates replication fork restart after DNA damage in Saccharomyces
      cerevisiae.
AB  - Replication fork stalling at a DNA lesion generates a damage signal that
      activates the Rad53 kinase, which plays a vital role in survival by stabilizing
      stalled replication forks. However, evidence that Rad53 directly modulates the
      activity of replication forks has been lacking, and the nature of fork
      stabilization has remained unclear. Recently, cells lacking the Psy2-Pph3
      phosphatase were shown to be defective in dephosphorylation of Rad53 as well as
      replication fork restart after DNA damage, suggesting a mechanistic link between
      Rad53 deactivation and fork restart. To test this possibility we examined the
      progression of replication forks in methyl-methanesulfonate (MMS)-damaged cells,
      under different conditions of Rad53 activity. Hyperactivity of Rad53 in pph3Delta
      cells slows fork progression in MMS, whereas deactivation of Rad53, through
      expression of dominant-negative Rad53-KD, is sufficient to allow fork restart
      during recovery. Furthermore, combined deletion of PPH3 and PTC2, a second,
      unrelated Rad53 phosphatase, results in complete replication fork arrest and
      lethality in MMS, demonstrating that Rad53 deactivation is a key mechanism
      controlling fork restart. We propose a model for regulation of replication fork
      progression through damaged DNA involving a cycle of Rad53 activation and
      deactivation that coordinates replication restart with DNA repair.

PMID- 18628398
TI  - NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter
      proximal nucleosome assembly.
AB  - The Negative Elongation Factor (NELF) is a transcription regulatory complex that
      induces stalling of RNA polymerase II (Pol II) during early transcription
      elongation and represses expression of several genes studied to date, including
      Drosophila Hsp70, mammalian proto-oncogene junB, and HIV RNA. To determine the
      full spectrum of NELF target genes in Drosophila, we performed a microarray
      analysis of S2 cells depleted of NELF and discovered that NELF RNAi affects many
      rapidly inducible genes involved in cellular responses to stimuli. Surprisingly,
      only one-third of NELF target genes were, like Hsp70, up-regulated by NELF
      depletion, whereas the majority of target genes showed decreased expression
      levels upon NELF RNAi. Our data reveal that the presence of stalled Pol II at
      this latter group of genes enhances gene expression by maintaining a permissive
      chromatin architecture around the promoter-proximal region, and that loss of Pol
      II stalling at these promoters is accompanied by a significant increase in
      nucleosome occupancy and a decrease in histone H3 Lys 4 trimethylation. These
      findings identify a novel, positive role for stalled Pol II in regulating gene
      expression and suggest that there is a dynamic interplay between stalled Pol II
      and chromatin structure.

PMID- 18628399
TI  - Genome-wide location analysis reveals a role of TFIIS in RNA polymerase III
      transcription.
AB  - TFIIS is a transcription elongation factor that stimulates transcript cleavage
      activity of arrested RNA polymerase II (Pol II). Recent studies revealed that
      TFIIS has also a role in Pol II transcription initiation. To improve our
      understanding of TFIIS function in vivo, we performed genome-wide location
      analysis of this factor. Under normal growth conditions, TFIIS was detected on
      Pol II-transcribed genes, and TFIIS occupancy was well correlated with that of
      Pol II, indicating that TFIIS recruitment is not restricted to NTP-depleted
      cells. Unexpectedly, TFIIS was also detected on almost all Pol III-transcribed
      genes. TFIIS and Pol III occupancies correlated well genome-wide on this novel
      class of targets. In vivo, some dst1 mutants were partly defective in tRNA
      synthesis and showed a reduced Pol III occupancy at the restrictive temperature.
      In vitro transcription assays suggested that TFIIS may affect Pol III start site
      selection. These data provide strong in vivo and in vitro evidence in favor of a
      role of TFIIS as a general Pol III transcription factor.

PMID- 18628400
TI  - Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping
      programs required for perinatal maturation of the heart.
AB  - Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial
      biogenesis to meet the high-energy demands after birth. PPARgamma coactivator-1
      (PGC-1) alpha and beta have been implicated in the transcriptional control of
      cellular energy metabolism. Mice with combined deficiency of PGC-1alpha and PGC
      1beta (PGC-1alphabeta(-/-) mice) were generated to investigate the convergence of
      their functions in vivo. The phenotype of PGC-1beta(-/-) mice was minimal under
      nonstressed conditions, including normal heart function, similar to that of PGC
      1alpha(-/-) mice generated previously. In striking contrast to the singly
      deficient PGC-1 lines, PGC-1alphabeta(-/-) mice died shortly after birth with
      small hearts, bradycardia, intermittent heart block, and a markedly reduced
      cardiac output. Cardiac-specific ablation of the PGC-1beta gene on a PGC-1alpha
      deficient background phenocopied the generalized PGC-1alphabeta(-/-) mice. The
      hearts of the PGC-1alphabeta(-/-) mice exhibited signatures of a maturational
      defect including reduced growth, a late fetal arrest in mitochondrial biogenesis,
      and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT)
      of PGC-1alphabeta(-/-) mice also exhibited a severe abnormality in function and
      mitochondrial density. We conclude that PGC-1alpha and PGC-1beta share roles that
      collectively are necessary for the postnatal metabolic and functional maturation
      of heart and BAT.

PMID- 18628402
TI  - Structural motifs of importance for the constitutive activity of the orphan 7TM
      receptor EBI2: analysis of receptor activation in the absence of an agonist.
AB  - The Epstein-Barr induced receptor 2 (EBI2) is a lymphocyte-expressed orphan seven
      transmembrane-spanning (7TM) receptor that signals constitutively through
      Galphai, as shown, for instance by guanosine 5'-O-(3-thio)triphosphate
      incorporation. Two regions of importance for the constitutive activity were
      identified by a systematic mutational analysis of 29 residues in EBI2. The cAMP
      response element-binding protein transcription factor was used as a measure of
      receptor activity and was correlated to the receptor surface expression. PheVI:13
      (Phe257), and the neighboring CysVI:12 (Cys256), in the conserved CW/FxP motif in
      TM 6, acted as negative regulators as Ala substitutions at these positions
      increased the constitutive activity 5.7- and 2.3-fold, respectively, compared
      with EBI2 wild type (wt). In contrast, ArgII:20 (Arg87) in TM-2 acted as a
      positive regulator, as substitution to Ala, but not to Lys, decreased the
      constitutive activity more than 7-fold compared with wt EBI2. IleIII:03 (Ile106)
      is located only 4 A from ArgII:20, and a favorable electrostatic interaction with
      ArgII:20 was created by introduction of Glu in III:03, given that the activity
      increased to 4.4-fold of that wt EBI2. It is noteworthy that swapping these
      charges by introduction of Glu in II:20 and Arg in III:03 resulted in a 2.7-fold
      increase compared with wt EBI2, thereby rescuing the two signaling-deficient
      single mutations, which exhibited a 3.8- to 4.5-fold decrease in constitutive
      activity. The uncovering of these molecular mechanisms for EBI2 activation is
      important from a drug development point of view, in that it may facilitate the
      rational design and development of small-molecule inverse agonists against EBI2
      of putative importance as antiviral- or immune modulatory therapy.

PMID- 18628401
TI  - Trim11 modulates the function of neurogenic transcription factor Pax6 through
      ubiquitin-proteosome system.
AB  - The transcription factor Pax6 is an important developmental regulator.
      Spatiotemporal control of Pax6 expression during embryogenesis is crucial for
      regulating distinct aspects of cortical development. Here, we report that Trim11,
      a member of the TRIM/RBCC protein family of E3 ubiquitin ligases, interacts with
      Pax6 and mediates Pax6 degradation via the ubiquitin-proteasome system. Trim11
      overexpression decreases endogenous Pax6 protein levels and represses Pax6
      functions, including Pax6-dependent transactivation and neurogenesis. Abrogation
      of endogenous Trim11 expression in the developing cortex increases the level of
      insoluble forms of Pax6 and enhances apoptosis. We provide evidence that the
      B30.2 domain of Trim11 is essential for the clearance of insoluble cell proteins.
      Furthermore, we show that the expression of Trim11 is directly regulated by Pax6
      in developing cortex in vivo. Our findings indicate that an autoregulatory
      feedback loop between Trim11 and Pax6 maintains a balance between the levels of
      Pax6 and Trim11 proteins in cortical progenitors, having an essential role for
      the Pax6-dependent neurogenesis.

PMID- 18628403
TI  - New insights into the function of M4 muscarinic acetylcholine receptors gained
      using a novel allosteric modulator and a DREADD (designer receptor exclusively
      activated by a designer drug).
AB  - The M4 muscarinic acetylcholine (ACh) receptor (mAChR) is a potential therapeutic
      target but characterized by a lack of subtype-selective ligands. We recently
      generated "designer receptors exclusively activated by a designer drug"
      (DREADDs), which contained mutations of two conserved orthosteric-site residues
      (Y113C/A203G in the M4 mAChR) that caused a loss of ACh activity but a gain in
      responsiveness to clozapine-N-oxide (CNO). The current study characterized the
      interactions of the wild type and the M4 DREADD with a range of agonists,
      antagonists, and the recently discovered M4 mAChR allosteric potentiator, 3-amino
      5-chloro-6-methoxy-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid
      cyclopropylamide (LY2033298). LY2033298 displayed positive binding cooperativity
      with ACh, neutral cooperativity with the antagonist, [3H]quinuclidinyl benzilate,
      and agonism for activation of phosphorylated extracellular signal-regulated
      kinase (ERK) 1/2 at the wild-type M4 mAChR. LY2033298's cooperativity with
      clozapine or CNO was weakly positive with respect to binding but profoundly
      negative with respect to LY2033298 signaling. Although the DREADD mutations
      increased the binding and function of clozapine-like compounds, all other
      agonists lost the ability to activate the mutant; for the orthosteric agonists
      ACh and pilocarpine, this was due partly to a reduced affinity, whereas the
      affinity of LY2033298 or the atypical agonist 4-I-[3-chlorophenyl]carbamoyloxy)-2
      butynyltrimethylammnonium chloride was unaltered. The interaction between
      LY2033298 and clozapine-like compounds reverted to neutral cooperativity on the
      DREADD, whereas LY2033298 caused a striking functional rescue of ACh potency and
      efficacy at the DREADD. These results provide conclusive evidence for the
      retention of a functional allosteric site on the M4 DREADD and highlight a role
      for residues Tyr113 and Ala203 in the transmission of cooperativity.

PMID- 18628404
TI  - The alpha1D-adrenergic receptor induces vascular smooth muscle apoptosis via a
      p53-dependent mechanism.
AB  - Activation of the endogenous alpha1-adrenergic receptor (AR) associated with
      human aortic smooth muscle cells resulted in a dose- and time-dependent increase
      in the levels of mitochondrial reactive oxygen species (ROS). ROS increases were
      apparent within 10 min and maximal after 45 min. Prolonged activation (>4 h) of
      the alpha1-AR resulted in smooth muscle cell apoptosis. Both the increase in ROS
      and apoptotic cell death were blocked by the nonselective alpha1-AR antagonist
      prazosin as well as the selective alpha1D-AR antagonist 8-[2-[4-(2-methoxyphenyl)
      1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7, 9-dione (BMY 7378). Increases in
      ROS and apoptosis produced by alpha1-AR activation were also blocked by the p38
      mitogen-activated protein kinase inhibitor 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)
      5-(4-pyridyl)-1H-imidazole (SB 202190) and the NAPDH oxidase inhibitor apocynin.
      The extracellular signal-regulated kinase 1/2 inhibitor 2'-amino-3'
      methoxyflavone (PD 98059) or the c-Jun NH2-terminal kinase inhibitor 1, 9
      pyrazoloanthrone anthra(1, 9-cd)pyrazol-6(2H)-one (SP 600125) was without effect
      on increases in ROS levels or apoptosis. Pifithrin-alpha, an inhibitor of the
      tumor suppressor protein p53, had no effect on ROS generation but did block
      alpha1D-AR-induced apoptosis. Activation of the alpha1D-AR resulted in
      translocation of p53 to the mitochondria. The mitochondrial translocation of p53
      was blocked by prazosin, BMY 7378, apocynin, SB 202190, and pifithrin-alpha.
      Apoptosis was also blocked by small interfering RNA directed against p53. These
      data show that the alpha1D-AR is coupled to the generation of mitochondrial ROS
      by a pathway involving p38 and NADPH oxidase. Sustained activation of the alpha1D
      AR results in smooth muscle cell apoptosis in a pathway that involves the tumor
      suppressor protein p53 and the mitochondrial translocation of p53. The data also
      provide evidence of a linkage between the alpha1D-AR and p53.

PMID- 18628406
TI  - CD56bright cells increase expression of {alpha}4 integrin at ovulation in fertile
      cycles.
AB  - Leukocyte content of human endometrium changes rapidly after ovulation,
      particularly as a result of gains in CD56(bright) uterine NK (uNK) cells. We have
      proposed that uNK precursor cells are found within the blood CD56(bright) pool
      and are recruited to decidualizing endometrium through functional changes in
      their adhesion molecules and chemokine receptors. This study sought to quantify
      alterations in adhesion molecules, cytokines, chemokines, and receptors induced
      in circulating CD56(+) cells of fertile and infertile women by ovulation. Blood
      was drawn from 12 fertile volunteers and six female-infertility patients at
      Menstrual Cycle Day (d) 5 and on the day following the preovulatory surge of
      luteinizing hormone (LH). CD56(bright), CD56(dim), and CD56(+)CD3(+) cell subsets
      were isolated and evaluated by flow cytometry, quantitative PCR, or Western
      blotting. In CD56(bright) cells from fertile but not infertile women, alpha(4)
      integrin increased between d5 and the preovulatory LH surge. CD56(dim) and NKT
      cells did not show a change in alpha(4) integrin but differed significantly
      between fertile and infertile donors, and infertile donors had reduced homing
      molecule expression in CD56(dim) and NKT cells, and at ovulation, their NKT cells
      showed elevated cytokine production. None of the circulating CD56(+) cell subsets
      had transcripts for receptors for estrogen, progesterone, LH, or prolactin. Thus,
      immunological events associated with the LH surge induce alterations in all
      subsets of CD56(+) cells, and the unique induction of alpha(4) integrin in
      CD56(bright) cells of fertile women constitutes a potential method to promote
      uterine homing.

PMID- 18628405
TI  - Health-related quality of life in patients with high-grade glioma.
AB  - Health-related quality of life (HRQOL) has become an increasingly important
      endpoint in cancer studies; however, the research into the HRQOL of patients with
      high-grade glioma (HGG) is sparse compared with that for patients with other
      neoplasms. Owing to the specific location and poor prognosis, it is more
      important and difficult to study HRQOL in patients with HGG than in those with
      other tumors; furthermore, the study of HRQOL in patients with HGG differs from
      that for patients with other tumors. In this review, we identified and compared
      the most frequently used instruments to assess HRQOL; analyzed specific facets
      and determinants of HRQOL (such as sex, tumor location and histological
      classification, depression, and cognitive function), as well as the association
      between HRQOL and survival; and appraised the effects of new treatments on HRQOL
      in patients with HGG from randomized controlled trials. Furthermore, we detected
      broadly existing problems and many contradictory outcomes and gave some proper
      interpretation and suggestions regarding them.

PMID- 18628407
TI  - Cancer survivorship research: opportunities and future needs for expanding the
      research base.

PMID- 18628408
TI  - Point/Counterpoint: Aspirin is clinically effective in chemoprevention of
      colorectal neoplasia: point.

PMID- 18628409
TI  - Point/Counterpoint: Aspirin should not be promoted for colon cancer prevention:
      counterpoint.

PMID- 18628410
TI  - Use of common medications and breast cancer risk.
AB  - Prescription and over-the-counter medications are widely used in the United
      States and many western countries. More than two-thirds of women ages >45 years,
      who are at greatest risk for breast cancer, take prescription medication. In
      light of the ubiquitous nature of medication use and the fact that breast cancer
      remains the most common cancer in women, research on the role of medication use
      in breast cancer etiology is warranted. We summarize the epidemiologic evidence
      on the association between breast cancer risk and use of common medications,
      including antibiotics, antidepressants, statins, antihypertensives, and
      nonsteroidal anti-inflammatory drugs. Overall, there is little evidence that
      would implicate the use of antibiotics, antidepressants, statins, and
      antihypertensives in the etiology of breast cancer. Although several prospective
      studies and a randomized low-dose aspirin chemoprevention trial have not shown
      lower risk of breast cancer among aspirin users, most studies that have examined
      the potential chemoprotective effect of nonsteroidal anti-inflammatory drugs have
      shown significant risk reductions for regular and prolonged use of these drugs.
      The existing literature on the role of medication use in breast carcinogenesis is
      complicated. Interpretation of the evidence is hampered due to major methodologic
      differences across studies, including exposure assessment, exposure
      classification, and adjustment for potential confounding variables. These
      differences largely stem from the fact that the majority of articles on this
      topic represent secondary data analyses from studies with inadequate information
      on exposure or confounders. Thus, future epidemiologic studies specifically
      designed to study these ubiquitous and biologically plausible exposures are
      warranted.

PMID- 18628411
TI  - Diet, autophagy, and cancer: a review.
AB  - A host of dietary factors can influence various cellular processes and thereby
      potentially influence overall cancer risk and tumor behavior. In many cases,
      these factors suppress cancer by stimulating programmed cell death. However,
      death not only can follow the well-characterized type I apoptotic pathway but
      also can proceed by nonapoptotic modes such as type II (macroautophagy-related)
      and type III (necrosis) or combinations thereof. In contrast to apoptosis, the
      induction of macroautophagy may contribute to either the survival or death of
      cells in response to a stressor. This review highlights current knowledge and
      gaps in our understanding of the interactions among bioactive food constituents,
      autophagy, and cancer. Whereas a variety of food components including vitamin D,
      selenium, curcumin, resveratrol, and genistein have been shown to stimulate
      autophagy vacuolization, it is often difficult to determine if this is a
      protumorigenic or antitumorigenic response. Additional studies are needed to
      examine dose and duration of exposures and tissue specificity in response to
      bioactive food components in transgenic and knockout models to resolve the
      physiologic implications of early changes in the autophagy process.

PMID- 18628412
TI  - A systematic review of the prevalence and attribution of human papillomavirus
      types among cervical, vaginal, and vulvar precancers and cancers in the United
      States.
AB  - OBJECTIVES: To describe prevalence and estimated attribution of human
      papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and
      cancers. METHODS: U.S. studies reporting HPV typing for cervical intraepithelial
      neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal
      intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were
      gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/).
      Selected studies had PCR testing data for > or =10 cases for a disease endpoint.
      Analytic methods augmented prior reviews of cervical disease with an updated and
      expanded analysis (including vulvar and vaginal disease), new selection criteria
      for specimens, and adjustment for histologic type, where possible, among pooled
      cancer cases. In addition, for analyses of estimated attribution of HPV types, we
      incorporated accounting methods for lesions infected with multiple HPV types.
      RESULTS: Data from 22 U.S. studies meeting review eligibility criteria were
      tabulated. Following adjustment for the presence of multiple HPV types in a
      single specimen, the top two HPV types contributing to disease were CIN 1 (HPV
      16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%),
      VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33;
      55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%).
      CONCLUSIONS: The HPV type distribution and proportion of cases testing positive
      for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal
      neoplasias and by grade of disease. Adjustment for the presence of multitype HPV
      infections can have an important effect on the estimated attribution of HPV types
      to disease, particularly for types other than HPV 16.

PMID- 18628413
TI  - Colorectal cancer test use from the 2005 National Health Interview Survey.
AB  - BACKGROUND: Screening is effective in reducing colorectal cancer mortality.
      Recommended colorectal cancer screening options include a home fecal occult blood
      test (FOBT) or colorectal endoscopy (sigmoidoscopy or colonoscopy). Past surveys
      have indicated that colorectal cancer screening prevalence in the United States
      is low. The purpose of this analysis was to determine the prevalence of
      colorectal cancer test use in the United States by various factors and to examine
      reasons for not having a colorectal cancer test. METHODS: Data on respondents
      ages > or =50 years from the 2005 National Health Interview Survey (n = 13,269)
      were analyzed. The proportion of the U.S. population that had home FOBT within
      the past year or endoscopy within the past 10 years was examined by
      sociodemographic, health-care access, and other health-related factors. Reported
      reasons for not having FOBT or endoscopy were also analyzed. RESULTS: The age
      standardized proportion of respondents who reported FOBT within the past year
      and/or endoscopy within the past 10 years was 50.0% [95% confidence interval (95%
      CI), 48.8-51.2]. Colorectal cancer testing rates were particularly low among
      people without health-care coverage (24.1%; 95% CI, 19.2-29.7) or without a usual
      source of health care (24.7%; 95% CI, 20.8-29.0). The most commonly reported
      reason for not having a colorectal cancer test was "never thought about it."
      CONCLUSIONS: In 2005, about half of Americans ages > or =50 years did not have
      appropriate colorectal cancer testing. Increased efforts to expand health-care
      coverage or to provide colorectal cancer tests to people without health-care
      coverage are needed to increase colorectal cancer screening.

PMID- 18628414
TI  - An object lesson: source determines the relations that trait anxiety, prostate
      cancer worry, and screening fear hold with prostate screening frequency.
AB  - Fears regarding prostate cancer and the associated screening are widespread.
      However, the relations between anxiety, cancer worry, and screening fear and
      screening behavior are complex, because anxieties stemming from different sources
      have different effects on behavior. In differentiating among anxieties from
      different sources (trait anxiety, cancer worry, and screening fear), we expected
      that cancer worry would be associated with more frequent screening, whereas fear
      of screening would be associated with less frequent screening. Hypotheses were
      tested in a sample of 533 men (ages 45-70 years) recruited using a stratified
      cluster-sampling plan. Men provided information on demographic and structural
      variables (age, education, income, marital status, physician discussion of risk
      and screening, access, and insurance) and completed a set of anxiety measures
      (trait anxiety, cancer worry, and screening fear). As expected, two-step multiple
      regressions controlling for demographics, health insurance status, physician
      discussion, and health-care system barriers showed that prostate-specific antigen
      and digital rectal examination frequencies had unique associations with cancer
      worry and screening fear. Specifically, whereas cancer worry was associated with
      more frequent screening, fear of screening was associated with less frequent
      screening at least for digital rectal examination; trait anxiety was
      inconsistently related to screening. Data are discussed in terms of their
      implications for male screening and the understanding of how anxiety motivates
      health behaviors. It is suggested that understanding the source of anxiety and
      the manner in which health behaviors such as cancer screenings may enhance or
      reduce felt anxiety is a likely key to understanding the associations between
      anxiety and behavioral outcomes.

PMID- 18628415
TI  - Sp1, a new biomarker that identifies a subset of aggressive pancreatic ductal
      adenocarcinoma.
AB  - Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths
      in the United States. Sp1 is a sequence-specific DNA binding protein that is
      important in the transcription of a number of regulatory genes involved in cancer
      cell growth, differentiation, and metastasis. In this study, we investigated Sp1
      expression in pancreatic ductal adenocarcinoma and its association with clinical
      outcome. We studied 42 patients with primary pancreatic adenocarcinoma. The
      expression of Sp1 in pancreatic adenocarcinoma was evaluated by
      immunohistochemical staining. All 42 patients had clinical follow-up information
      and were evaluated for survival. Sp1 protein was aberrantly overexpressed in a
      subset of primary pancreatic adenocarcinoma. These tumors all developed
      metastasis, whereas none of the primary tumors without lymph node metastasis
      showed Sp1 overexpression. Statistically, Sp1 overexpression was associated with
      higher stage, higher grade, and lymph node metastasis (P < 0.001, P = 0.036, and
      P < 0.0001, respectively). Additionally, patients of this subset had a much
      shorter overall survival than patients without Sp1 overexpression, as evidenced
      by Kaplan-Meier plots and the log-rank test (P = 0.002). The 5-year overall
      survival rate was 19% in patients with Sp1 overexpression, compared with 55% in
      patients without Sp1 overexpression. The median survival was only 13 months for
      patients with Sp1 overexpression, compared with 65 months for patients without
      Sp1 overexpression. In conclusion, Sp1 is a new biomarker that identifies a
      subset of pancreatic ductal adenocarcinoma with aggressive clinical behavior. It
      can be used at initial diagnosis of pancreatic adenocarcinoma to identify
      patients with an increased probability of cancer metastasis and much shortened
      overall survival.

PMID- 18628416
TI  - Human aflatoxin albumin adducts quantitatively compared by ELISA, HPLC with
      fluorescence detection, and HPLC with isotope dilution mass spectrometry.
AB  - Essential to the conduct of epidemiologic studies examining aflatoxin exposure
      and the risk of heptocellular carcinoma, impaired growth, and acute toxicity has
      been the development of quantitative biomarkers of exposure to aflatoxins,
      particularly aflatoxin B(1). In this study, identical serum sample sets were
      analyzed for aflatoxin-albumin adducts by ELISA, high-performance liquid
      chromatography (HPLC) with fluorescence detection (HPLC-f), and HPLC with isotope
      dilution mass spectrometry (IDMS). The human samples analyzed were from an acute
      aflatoxicosis outbreak in Kenya in 2004 (n = 102) and the measured values ranged
      from 0.018 to 67.0, nondetectable to 13.6, and 0.002 to 17.7 ng/mg albumin for
      the respective methods. The Deming regression slopes for the HPLC-f and ELISA
      concentrations as a function of the IDMS concentrations were 0.71 (r(2) = 0.95)
      and 3.3 (r(2) = 0.96), respectively. When the samples were classified as cases or
      controls, based on clinical diagnosis, all methods were predictive of outcome (P
      < 0.01). Further, to evaluate assay precision, duplicate samples were prepared at
      three levels by dilution of an exposed human sample and were analyzed on three
      separate days. Excluding one assay value by ELISA and one assay by HPLC-f, the
      overall relative SD were 8.7%, 10.5%, and 9.4% for IDMS, HPLC-f, and ELISA,
      respectively. IDMS was the most sensitive technique and HPLC-f was the least
      sensitive method. Overall, this study shows an excellent correlation between
      three independent methodologies conducted in different laboratories and supports
      the validation of these technologies for assessment of human exposure to this
      environmental toxin and carcinogen.

PMID- 18628417
TI  - High excretion of etheno adducts in liver fluke-infected patients: protection by
      praziquantel against DNA damage.
AB  - Chronic infection by Opisthorchis viverrini (OV) is a strong risk factor for
      developing cholangiocarcinoma (CCA). To clarify the involvement of oxidative
      stress and lipid peroxidation (LPO)-derived DNA damage, the excretion of LPO
      derived etheno DNA adducts was measured in urine samples collected from healthy
      volunteers and OV-infected Thai subjects. 1,N(6)-etheno-2'-deoxyadenosine
      (epsilondA) and 3,N(4)-etheno-2'-deoxycytidine (epsilondC) levels were quantified
      by immunoprecipitation/high-performance liquid chromatography/fluorescence
      detection and (32)P-postlabeling TLC. Excreted etheno adduct levels were related
      to indicators of inflammatory conditions [malondialdehyde (MDA) and
      nitrate/nitrite levels in urine and plasma alkaline phosphatase (ALP) activity].
      Mean epsilondA and epsilondC levels were 3 to 4 times higher in urine of OV
      infected patients; MDA, nitrate/nitrite, and ALP were also increased up to 2
      fold. MDA and ALP were positively related to epsilondA excretion. Two months
      after a single dose of the antiparasitic drug Praziquantel, epsilondA and
      epsilondC concentrations in urine of OV-infected subjects were decreased; MDA,
      nitrate/nitrite, and ALP were concomitantly lowered. We conclude that chronic OV
      infection through oxidative/nitrative stress leads to increased urinary excretion
      of the etheno-bridged deoxyribonucleosides, reflecting high LPO-derived DNA
      damage in vivo. These promutagenic DNA etheno adducts in bile duct epithelial
      cells may increase the risk of OV-infected patients to later develop CCA. Urinary
      epsilondA and epsilondC levels should be explored (a) as noninvasive risk markers
      for developing opisthorchiasis-related CCA and (b) as promising biomarkers to
      assess the efficacy of preventive and therapeutic interventions.

PMID- 18628418
TI  - Successful coordination and execution of nontherapeutic studies in a cooperative
      group setting: lessons learned from Children's Oncology Group studies.
AB  - The immense progress made in childhood cancer survival has been due to the
      systematic and efficient conduct of large multicenter therapeutic trials, using
      the infrastructure developed by national cooperative groups. These therapeutic
      trials have been successful, in part due to the high participation rates by the
      participating member institutions. However, participation in nontherapeutic
      trials in the cooperative group setting has lagged behind that of therapeutic
      trials for a variety of reasons, such as lack of institutional resources, leading
      to low priority given to such activities. The purpose of this report is to share
      some of the methods developed and successfully implemented by a coordinating
      center (City of Hope National Medical Center) to maximize institutional
      participation and patient enrollment and to standardize data collection and
      quality control, in order to ensure the successful execution of two large,
      extramurally funded, cooperative group nontherapeutic studies. To date, over 175
      institutions have obtained regulatory approval for the protocols showcased here,
      accrual has been on target, and completeness and quality of the collected data
      have been excellent. The successful execution of these nontherapeutic studies
      shows the advantages of diverse study publicity techniques, detailed standardized
      operating procedures, and effective utilization of technological resources.

PMID- 18628419
TI  - Increases in serum estrone sulfate level are associated with increased
      mammographic density during menopausal hormone therapy.
AB  - BACKGROUND: Menopausal hormone therapy increases mammographic density. We
      determined whether increases in serum estrone sulfate (E(1)S) levels during
      menopausal hormone therapy predict increased mammographic density. METHODS: We
      measured percent mammographic density and serum E(1)S levels in 428 participants
      of the Postmenopausal Estrogen/Progestin Interventions study who were randomly
      assigned to daily conjugated equine estrogen (CEE) 0.625 mg alone, CEE + daily
      medroxyprogesterone acetate (MPA) 2.5 mg, CEE + cyclical MPA (10 mg days 1-12 per
      28-day cycle), or CEE + cyclical micronized progesterone (10 mg days 1-12). Serum
      E(1)S levels were determined by RIA. Information about covariates was determined
      by annual questionnaire. Using linear regression, we determined the association
      between change in E(1)S level from baseline to 12 months and change in percent
      mammographic density (by semiquantitative interactive threshold method). RESULTS:
      After controlling for baseline mammographic density, age, body mass index,
      alcohol intake, parity, smoking, ethnicity, physical activity, and age at first
      pregnancy, mammographic density increased by 1.3% for every 1 ng/mL increase in
      E(1)S level (P < 0.0001). The association between change in E(1)S level and
      change in mammographic density differed by treatment group (greater effect in CEE
      + cyclical MPA group versus CEE group; P = 0.05). After controlling for treatment
      group, change in the ratio of E(1)S to E(1) was also positively associated with
      change in mammographic density. CONCLUSIONS: Increases in serum E(1)S levels
      during menopausal hormone therapy are associated with increases in mammographic
      density. The relative contribution of E(1)S and E(1) to stimulation of breast
      tissue awaits further elucidation.

PMID- 18628420
TI  - Association of aryl hydrocarbon receptor gene polymorphisms and urinary 1
      hydroxypyrene in polycyclic aromatic hydrocarbon-exposed workers.
AB  - Polycyclic aromatic hydrocarbons (PAH) in coke oven emissions could cause lung
      cancer in human. Individual's genotype of the metabolic enzymes and early
      biological changes were known to be associated with the susceptibility of cancer
      development. Knowledge of metabolic gene polymorphisms, which affect on the
      urinary 1-hydroxypyrene (1-OHP), could benefit us in understanding the
      interindividual difference in the mechanism of PAH-induced carcinogenesis. In
      this study, we investigated the association of aryl hydrocarbon receptor (AhR)
      gene polymorphisms and urinary 1-OHP. One hundred forty-seven workers exposed to
      PAH and 69 nonexposure workers were recruited. Seven tagging single nucleotide
      polymorphisms in AhR gene were selected by pariwise r(2) method and minor allele
      frequency cutoff of 0.05 from Chinese genotype data in HapMap project. These
      seven tagging single nucleotide polymorphisms were genotyped by PCR-based
      methods. Multivariate analysis of covariance revealed that the levels of 1-OHP in
      PAH-exposed workers carrying genotype CT were lower than workers carrying wild
      genotype TT at loci rs10250822 and rs2282885 of AhR gene (P = 0.032 and 0.044,
      respectively). In PAH-exposed workers, the urinary 1-OHP levels showed a linear
      correlation (P(trend) = 0.041) with the genotypes at locus rs2282885, especially
      in low and moderate exposure groups. In contrast, no significant association was
      found between urinary 1-OHP level and AhR genotypes among nonexposed workers. Our
      findings indicated that polymorphisms of AhR gene were associated with the level
      of 1-OHP among PAH-exposed workers, suggesting that AhR-mediated signaling might
      contribute to individual susceptibility to PAH exposure.

PMID- 18628421
TI  - Breast density assessment in adolescent girls using dual-energy X-ray
      absorptiometry: a feasibility study.
AB  - Breast density, the radiographically opaque fraction of the breast in a
      mammogram, is one of the strongest biomarkers of breast cancer risk. However,
      younger populations do not typically have mammograms due to radiation concerns.
      This study explored a commercially available dual-energy X-ray absorptiometer
      (DXA) system as a low-dose method to measure breast fibroglandular density in
      adolescent girls. Eighteen girls (13-14 years old) indicated their breast
      development according to Tanner and underwent three dedicated DXA scans, two of
      their left and one of their right breasts. Total projected breast area was
      manually delineated on each image and percent fibroglandular volume density
      (%FGV), absolute fibroglandular volume (FGV), total breast area, and volume were
      computed. It was possible to image breasts representing all five Tanner stages;
      %FGV ranged from 31.9% to 92.2% with a mean of 71.1 +/- 14.8%, whereas FGV ranged
      from 80 to 270 cm(3) with a mean of 168 +/- 54 cm(3). Left and right breast %FGV
      were highly correlated (r(p) = 0.97, P < 0.0001) and of the same magnitude (P =
      0.18). However, left total volume and FGV were larger than the right by 38 cm(3)
      (P = 0.04) and 19 cm(3) (P = 0.02), respectively. Total volume and FGV increased
      by Tanner stage, whereas %FGV did not. Our method had excellent precision for
      %FGV and moderate precision for FGV (root mean square SDs of 2.4% and 16.6
      cm(3)). These pilot data indicate that dedicated DXA breast scans may be useful
      in studies exploring breast density in girls.

PMID- 18628422
TI  - No reduction in C-reactive protein following a 12-month randomized controlled
      trial of exercise in men and women.
AB  - Low-grade systemic inflammation is suggested to play a role in the development of
      several chronic diseases including cancer. Higher levels of physical activity and
      lower adiposity have been associated with reduced levels of markers of systemic
      inflammation, such as C-reactive protein (CRP); however, reductions in CRP have
      not been consistently observed in randomized controlled trials of exercise.
      PURPOSE: To examine the effect of a 12-month aerobic exercise intervention on CRP
      levels in men and women. METHODS: One hundred two men and 100 women, sedentary
      and of ages 40 to 75 years, with mean body mass index (BMI) of 29.9 and 28.7
      kg/m(2), respectively, were randomly assigned to a 12-month moderate-to-vigorous
      aerobic exercise intervention (6 d/wk, 60 min/d, 60-85% maximum heart rate) or
      control group. Fasting blood samples were collected at baseline and at 12 months.
      CRP levels were measured by high-sensitivity latex-enhanced nephelometry.
      RESULTS: At baseline, CRP was 1.16 and 2.11 mg/L for men and women, respectively,
      and CRP was correlated with percent body fat (r = 0.48, P < or =0.001), BMI (r =
      0.37, P < or = 0.001), and aerobic fitness (r = -0.49, P < or = 0.001). No
      intervention effects were observed for CRP in men or women, or when stratified by
      baseline BMI (<30 versus > or =30 kg/m(2)), baseline CRP (<3 versus > or =3
      mg/L), or change in body weight, body composition, or aerobic fitness.
      CONCLUSION: A 12-month moderate-to-vigorous aerobic exercise intervention did not
      affect CRP levels in previously sedentary men or women with average-risk CRP
      values at baseline.

PMID- 18628423
TI  - Serum insulin-like growth factor-I and platelet-derived growth factor as
      biomarkers of breast cancer prognosis.
AB  - Epidemiologic studies have shown that growth factors and inflammatory mechanisms
      may affect breast cancer risk and prognosis. The present analysis on 110
      postmenopausal breast cancer patients tested if serum insulin-like growth factor
      I (IGF-I), platelet-derived growth factor (PDGF), fructosamine, and C-reactive
      protein, a serum marker of inflammation, are associated with breast cancer
      relapse. The risk of adverse events after 5.5 years of follow-up was examined by
      Cox proportional hazards modeling, controlling for hormone receptor status, stage
      at diagnosis, and for body weight and serum testosterone level, which were known
      to significantly affect prognosis. PDGF and, to a lesser extent, IGF-I were
      positively but not significantly associated with the risk of breast cancer
      recurrence. By combining PDGF and IGF-I, however, the adjusted hazard ratio of
      recurrence among the women with both PDGF and IGF-I levels > their median values
      (respectively, 9.3 and 174.4 ng/mL) was 6.4 (95% confidence interval, 1.5-26.7)
      compared with the women with PDGF and IGF-I levels < or = their median values.
      Fructosamine and C-reactive protein were not associated with recurrences. The
      results suggest that PDGF may be an important prognostic factor for breast cancer
      and that IGF-I may increase the risk of recurrence in the presence of high PDGF
      levels.

PMID- 18628425
TI  - Human papillomavirus infection in Ulaanbaatar, Mongolia: a population-based
      study.
AB  - Data on human papillomavirus (HPV) and cervical cancer burden in Central Asia are
      scarce. To investigate HPV infection in Ulaanbaatar, the capital of Mongolia, we
      obtained cervical cell specimens from a population of 969 women ages 15 to 59
      years. DNA of 44 HPV types was detected using a GP5+/6+ PCR-based assay.
      Seropositivity for L1 proteins of HPV 16, 18, 31, 33, 45, 52, and 58 was assessed
      using multiplex HPV serology. Cytologic abnormalities were detected in 127 women
      (13.1%), among whom 6 cervical intraepithelial neoplasia grade 3 and 2 invasive
      cervical cancers were diagnosed. Overall HPV DNA prevalence was 35.0%, being
      highest (48.5%) in women ages <25 years. High-risk types were detected in 24.5%
      of women. HPV DNA prevalence declined with age but remained >25% in all age
      groups. HPV seroprevalence was also very high (38.0%) and increased steadily from
      33.2% to 48.9% in women ages <25 and 50 to 59 years, respectively. However, the
      proportion of women positive for both HPV markers of any individual HPV type was
      low. HPV16 was the most frequently detected type by PCR (6.1%), serology (23.0%),
      or both (2.1%). Lifetime number of sexual partners and induced abortions were
      shown to be directly associated with HPV DNA and/or seroprevalence. HPV
      prevalence in Ulaanbaatar was higher than that detected by similar HPV testing
      protocols in other populations in Asia or elsewhere and would suggest an
      important, yet unquantified, cervical cancer burden. Improving cervical cancer
      prevention, through screening and HPV vaccination, is an important public health
      issue for Mongolia.

PMID- 18628424
TI  - Breast cancer risk and hormone receptor status in older women by parity, age of
      first birth, and breastfeeding: a case-control study.
AB  - BACKGROUND: Early age at first birth and multiparity reduce the risk of estrogen
      receptor-progesterone receptor (ERPR)-positive breast cancer, whereas
      breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers.
      METHODS: We used multivariable logistic regression analysis to investigate
      whether age at first birth (<25 or > or =25 years) and breastfeeding (ever/never)
      modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative
      cancer using 1,457 incident breast cancer cases and 1,455 controls ages > or =55
      years who participated in the Women's Contraceptive and Reproductive Experiences
      Study. RESULTS: Women who gave birth before age 25 years had a 36% reduced risk
      of breast cancer compared with nulligravida that was not observed for women who
      started their families at an older age (P(heterogeneity) = 0.0007). This
      protective effect was restricted to ERPR-positive breast cancer (P(heterogeneity)
      = 0.004). Late age at first birth increased the risk of ERPR-negative cancers.
      Additional births reduced the risk of ERPR-positive cancers among women with an
      early first birth (P(trend) = 0.0001) and among women who breastfed (P(trend) =
      0.004) but not among older mothers or those who never breastfed. In women with a
      late first birth who never breastfed, multiparity was associated with increased
      risk of breast cancer. CONCLUSIONS: These findings suggest that the effect of
      parity on a woman's long-term risk of breast cancer is modified by age at first
      full-term pregnancy and possibly by breastfeeding.

PMID- 18628426
TI  - The hOGG1 Ser326Cys polymorphism and lung cancer risk: a meta-analysis.
AB  - The potentially functional polymorphism Ser326Cys in the human 8-oxoguanine DNA
      glycosylase (hOGG1) gene has been implicated in lung cancer risk, but published
      studies have mixed findings. To summarize published data, we did a comprehensive
      meta-analysis. Two investigators extracted data independently from 17 case
      control studies published in the PubMed using the search phrases "hOGG1/OGG1/OGG
      and polymorphism/genetic variation and lung cancer." The meta-analysis included
      6,375 cancer cases and 6,406 control subjects. The results showed that
      individuals carrying the hOGG1 Cys/Cys genotype did not have significantly
      increased risk of lung cancer [odds ratios (OR), 1.15; 95% (confidence interval)
      CI, 0.94-1.41] compared with those with the Ser/Ser genotype; similarly, no
      significant association with lung cancer risk was found either in the recessive
      (OR, 1.09; 95% CI, 0.90-1.32 for Cys/Cys versus Ser/Cys+Ser/Ser) or dominant
      model of the Ser326 allele (OR, 1.06; 95% CI, 0.93-1.21 for Cys/Cys+Ser/Cys
      versus Ser/Ser). However, significantly increased risks were found among Asian
      subjects (OR, 1.18; 95% CI, 1.01-1.38 for Cys/Cys+Ser/Cys versus Ser/Ser) in a
      dominant model. In stratified analyses by control source, compared with the
      Ser/Ser genotype, lung cancer risk associated with the hOGG1 Cys/Cys genotype was
      significantly increased in population-based studies (OR, 1.32; 95% CI, 1.04-1.67)
      but not in hospital-based studies (OR, 1.18; 95% CI, 0.98-1.42); in stratified
      analyses by the smoking status, however, the increased risk was observed only
      among nonsmokers in a dominant model (OR, 1.32; 95% CI, 1.04-1.67). The meta
      analysis suggested that a careful matching should be considered in future larger
      genetic association studies including multiple ethnic groups.

PMID- 18628427
TI  - A prospective study of bowel motility and related factors on breast cancer risk.
AB  - BACKGROUND: Estrogen is an established risk factor for breast cancer. Greater
      bowel motility has been associated with increased estrogen excretion and lower
      serum estrogen levels, suggesting that it may influence breast cancer risk.
      However, only one other epidemiologic study thus far, to our knowledge, has
      examined the relation between bowel motility and breast cancer risk. METHODS: We
      prospectively examined whether bowel motility, measured by self-reported
      frequency of bowel movements, and related factors (constipation, laxative use,
      water consumption, and dietary fiber intake) were associated with incidence of
      breast cancer among 28,586 postmenopausal women, ages 50 to 76 years, in the
      Vitamins and Lifestyle study. Cox proportional hazards models were used to
      estimate multivariate-adjusted relative risks (RR) and 95% confidence intervals
      (95% CI). From 2000 to 2005, 507 incident invasive breast cancers among the
      cohort were identified. RESULTS: Women with very frequent (> or =3/d) bowel
      movements had a 46% decreased risk compared with 1/d women (RR, 0.54; 95% CI,
      0.31-0.92), but the test for linear trend was not significant (P(trend) = 0.41).
      Constipation was nonsignificantly associated with increased risk (RR, 1.30 for >
      or =1/wk versus <1/y; 95% CI, 0.87-1.95). No statistically significant
      associations were observed for the other study exposures: 10-year chemical
      laxative use, 10-year use of fiber laxatives, water consumption, and dietary
      fiber intake. CONCLUSION: This study adds limited support to the hypothesis that
      increased bowel motility lowers breast cancer risk.

PMID- 18628428
TI  - Polymorphisms in genes involved in sex hormone metabolism, estrogen plus
      progestin hormone therapy use, and risk of postmenopausal breast cancer.
AB  - Hormone therapy, estrogen plus progestin (E+P) particularly, is associated with
      increased risk of breast cancer. Functionally relevant polymorphisms in genes
      involved in sex hormone metabolism may alter exposure to exogenous sex hormones
      and affect risk of postmenopausal breast cancer. We evaluated associations of
      common polymorphisms in genes involved in estrogen and/or progesterone
      metabolism, E+P use, and their interactions with breast cancer risk in a case
      control study of postmenopausal women (324 cases; 651 controls) nested within the
      VITAL cohort. None of the polymorphisms studied was, by itself, statistically
      significantly associated with breast cancer risk. E+P use was significantly
      associated with increased breast cancer risk (> or =10 years versus never; odds
      ratio, 1.9; 95% confidence interval, 1.3-2.8; P(trend) = 0.0002). Statistically
      significant interactions between CYP1A1 Ile(462)Val (P(interaction) = 0.04),
      CYP1A1 MspI (P(interaction) = 0.003), CYP1B1 Val(432)Leu (P(interaction) =
      0.007), CYP1B1 Asn(453)Ser (P(interaction) = 0.04) and PGR Val(660)Leu
      (P(interaction) = 0.01), and E+P use were observed. The increased risk of breast
      cancer associated with E+P use was greater among women with at least one rare
      allele of the CYP1A1 Ile(462)Val, CYP1A1 MspI, CYP1B1 Asn(453)Ser, and PGR
      Val(660)Leu polymorphisms than among women homozygous for the common allele of
      these polymorphisms. Risk of breast cancer increased little with increasing years
      of E+P use among women with at least one CYP1B1 Val(432) allele; a large increase
      in risk was seen among women homozygous for CYP1B1 Leu(432). Our results support
      the hypothesis that specific polymorphisms in genes involved in sex hormone
      metabolism may modify the effect of E+P use on breast cancer risk.

PMID- 18628429
TI  - GSTM1 and GSTT1 gene deletions and the risk for nasopharyngeal carcinoma in Han
      Chinese.
AB  - Southern China is a major nasopharyngeal carcinoma-endemic region. Environmental
      factors and genetic susceptibility contribute to nasopharyngeal carcinoma
      development in this area. Polymorphic deletions of GSTM1 and GSTT1 genes involved
      in the detoxification of potentially carcinogenic agents may be a risk factor for
      nasopharyngeal carcinoma. To investigate the roles of genetic variations of GSTM1
      and GSTT1 in nasopharyngeal carcinoma susceptibility in the Chinese population,
      we conducted a case-control study of 350 nasopharyngeal carcinoma cases and 622
      controls. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR
      assays. Logistic regression analysis was used to estimate odds ratios and 95%
      confidence intervals (95% CI). No significant association was observed for either
      GSTM1- or GSTT1-null genotype independently in the contribution to nasopharyngeal
      carcinoma risk. To explore possible joint effects of the GSTM1- and GSTT1-null
      polymorphisms with each other and with other risk factors for nasopharyngeal
      carcinoma, we examined the association between each combined genotype and the
      risk for nasopharyngeal carcinoma stratified by gender and EBV replication
      status. We found that individuals who carried GSTM1/GSTT1-double null genotype
      had a higher risk for nasopharyngeal carcinoma in the male population (odds
      ratio, 1.76; 95% confidence interval, 1.04-2.97; P = 0.03); however, this was not
      significant after correction for multiple comparisons. No statistical difference
      was found between cases and controls in females and the subpopulation positive
      for immunoglobulin A antibodies to EBV capsid antigen for combined genotypes. Our
      results suggest that the GSTM1/GSTT1-double null genotype may be a risk factor
      for nasopharyngeal carcinoma among males in southern China, but this result
      warrants confirmation in other studies.

PMID- 18628430
TI  - Extensive metabolic activation of the tobacco-specific carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone in smokers.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen
      present in both unburned tobacco and cigarette smoke. The sum of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, referred
      to as total NNAL, is an established urinary biomarker of human NNK uptake.
      Metabolic activation of NNK to DNA adducts proceeds via alpha-hydroxylation
      pathways, and 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3
      pyridyl)butanoic acid (hydroxy acid) are the principal end products of these
      pathways in rodents and primates. The purpose of this study was to determine NNK
      metabolic activation in smokers, as measured by the sum of keto acid and hydroxy
      acid, relative to total NNAL. To specifically identify NNK-derived keto acid and
      hydroxy acid, which are also formed from nicotine, we added [pyridine-D(4)]NNK to
      cigarettes that were originally low in NNK, and measured the deuterium-labeled
      metabolites in the urine of people who smoked these cigarettes. The total amount
      of [pyridine-D(4)]keto acid plus [pyridine-D(4)]hydroxy acid averaged 4.00 +/-
      2.49 nmol/24 h, whereas the average amount of total [pyridine-D(4)]NNAL was 0.511
      +/- 0.368 nmol/24 h. The results of this study show for the first time that NNK
      metabolic activation is a quantitatively significant pathway in smokers,
      accounting for approximately 86% of total urinary excretion of NNK metabolites.
      The large interindividual variation in the excreted [pyridine-D(4)]keto acid and
      [pyridine-D(4)]hydroxy acid among 20 smokers strongly supports our hypothesis
      that some smokers activate NNK more extensively than others and that the ratio
      between biomarkers of metabolic activation and detoxification at a given dose of
      NNK could be a potential indicator of cancer risk.

PMID- 18628431
TI  - Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or
      CpG island methylator phenotype.
AB  - Colorectal cancers arising from serrated polyps are characterized by the CpG
      island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto
      oncogene. Few epidemiologic studies have investigated risk factors for these
      tumors. We conducted a cohort study of 41,328 residents of Melbourne, Australia
      that included 9,939 participants of southern European origin and 31,389 of Anglo
      Celtic origin. Colorectal adenocarcinomas were identified from population-based
      cancer registries. BRAF V600E mutation in tumors was determined using a PCR-based
      allelic discrimination method. Tumors were classified as CIMP positive when at
      least three of five markers (RUNX3, CACNA1G, SOCS1, NEUROG1, and IGF2) were
      methylated according to MethyLight analysis. Hazard ratios (HR) and 95%
      confidence intervals (95% CI) were estimated by Cox regression with adjustment
      for risk factors for colorectal cancer. During follow-up, 718 participants were
      diagnosed with colorectal cancer. CIMP assays were done for 579 and BRAF V600E
      mutation testing for 582. After adjustment for other risk factors, when compared
      with people of Anglo-Celtic origin, those of southern European origin had lower
      incidence of colorectal cancer that had CIMP (HR, 0.32; 95% CI, 0.16-0.67) or
      BRAF mutations (HR, 0.30; 95% CI, 0.16-0.58) but similar incidence of colorectal
      cancer without CIMP (HR, 0.86; 95% CI, 0.70-1.05) or BRAF (HR, 0.90; 95% CI, 0.74
      1.11). People of southern European origin had lower risk of colorectal cancers
      with CIMP and BRAF mutation than people of Anglo-Celtic origin, which may in part
      be due to genetic factors that are less common in people of southern European
      origin.

PMID- 18628432
TI  - Performance of amplified DNA in an Illumina GoldenGate BeadArray assay.
AB  - Whole genome amplification (WGA) offers a means to enrich DNA quantities for
      epidemiologic studies. We used an ovarian cancer study of 1,536 single nucleotide
      polymorphisms (SNPs) and 2,368 samples to assess performance of multiple
      displacement amplification (MDA) WGA using an Illumina GoldenGate BeadArray.
      Initial screening revealed successful genotyping for 93.4% of WGA samples and
      99.3% of genomic samples, and 93.2% of SNPs for WGA samples and 96.3% of SNPs for
      genomic samples. SNP failure was predicted by Illumina-provided designability
      rank, %GC (P < or = 0.002), and for WGA only, distance to telomere and Illumina
      provided SNP score (P < or = 0.002). Distance to telomere and %GC were highly
      correlated; adjustment for %GC removed the association between distance to
      telomere and SNP failure. Although universally high, per-SNP call rates were
      related to designability rank, SNP score, %GC, minor allele frequency, distance
      to telomere (P < or = 0.01), and, for WGA only, Illumina-provided validation
      class (P < 0.001). We found excellent concordance generally (>99.0%) among 124
      WGA:genomic replicates, 15 WGA replicates, 88 replicate aliquots of the same WGA
      preparation, and 25 genomic replicates. Where there was discordance, it was
      across WGA:genomic replicates but limited to only a few samples among other
      replicates suggesting the introduction of error. Designability rank and SNP score
      correlated with WGA:genomic concordance (P < 0.001). In summary, use of MDA WGA
      DNA is feasible; however, caution is warranted regarding SNP selection and
      analysis. We recommend that biological SNP characteristics, notably distance to
      telomere and GC content (<50% GC recommended), as well as Illumina-provided
      metrics be considered in the creation of GoldenGate assays using MDA WGA DNA.

PMID- 18628434
TI  - Genetic polymorphisms of CYP2E1 and risk of colorectal adenomas in the Self
      Defense Forces Health Study.
AB  - CYP2E1 is an enzyme involved in the metabolism of N-nitrosamines and other
      carcinogenic substances. Functional RsaI and 96-bp insertion polymorphisms in 5'
      flanking region have drawn interest in relation to the risk of colorectal cancer.
      We investigated the relation of these genetic polymorphisms and colorectal
      adenoma, a well-established precursor lesion of colorectal cancer. Subjects were
      455 cases of colorectal adenomas and 1,052 controls of normal colonoscopy among
      men receiving a preretirement health examination in the Self Defense Forces.
      Genotypes were determined by either PCR-RFLP or PCR method. Statistical
      adjustment was made for smoking, alcohol use, body mass index, physical activity,
      and others. Individuals with RsaI c2 allele showed a decreased risk of proximal
      colon adenomas; adjusted odds ratios (95% confidence interval) of proximal and
      distal adenomas for the c1/c2 or c2/c2 genotype versus c1/c1 was 0.61 (0.41-0.88)
      and 0.95 (0.71-1.27), respectively. CYP2E1 96-bp insertion allele was associated
      with an increased risk of large (> or = 5 mm) adenomas; adjusted odds ratios (95%
      confidence interval) of large and small adenomas for having at least one
      insertion allele were 1.41 (1.03-1.94) and 0.94 (0.71-1.25), respectively. A
      suggestive effect modification was noted for alcohol consumption on the
      association between RsaI polymorphism and proximal adenomas (P(interaction) =
      0.09) as well as on the association between 96-bp insertion and large adenomas
      (P(interaction) = 0.05). These findings indicate that variation in activity and
      inducibility of CYP2E1 contribute to the development of colorectal
      carcinogenesis.

PMID- 18628433
TI  - Cervical and vulvar cancer risk in relation to the joint effects of cigarette
      smoking and genetic variation in interleukin 2.
AB  - Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the
      development of cervical and vulvar squamous cell carcinoma (SCC), and may
      influence risk through an immunosuppressive pathway. Genetic variation in
      interleukin 2 (IL2), associated in some studies with the inhibition of HPV
      targeted immunity, may modify the effect of smoking on the risk of HPV-related
      anogenital cancers. We conducted a population-based case-only study to measure
      the departure from a multiplicative joint effect of cigarette smoking and IL2
      variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs
      (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486
      vulvar SCC cases who had been interviewed regarding their smoking history.
      Compared with cases carrying the rs2069762 TT genotype, we observed significant
      departures from multiplicativity for smoking and carriership of the TG or GG
      genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence
      interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with
      cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC;
      IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI,
      0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar
      cancer risk. For cervical SCC, departure from multiplicativity was observed for
      smokers homozygous for the rs2069763 variant allele (TT versus GG or GT
      genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC
      diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and
      vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2.

PMID- 18628435
TI  - Serum beta-glucuronidase activity in response to fruit and vegetable
      supplementation: a controlled feeding study.
AB  - BACKGROUND: Fruit and vegetable (F&V) intake may lower the risk of some cancers.
      One hypothesized, but understudied, chemopreventive mechanism is that plant food
      constituents inhibit beta-glucuronidase, an acid hydrolase that deconjugates
      glucuronides. METHODS: We conducted a crossover feeding trial in 63 healthy women
      and men ages 20 to 40 years to examine the effect of diet on serum beta
      glucuronidase activity. Participants were randomized to two 2-week experimental
      diets with an intervening washout period: a diet high in selected citrus fruit,
      crucifers, and soy (F&V) and a diet devoid of fruits, vegetables, and soy
      (basal). Serum beta-glucuronidase activity was measured during the
      preintervention, F&V, and basal periods. Linear mixed models were used to obtain
      effect estimates and 95% confidence intervals (95% CI). RESULTS: We observed
      statistically significantly higher beta-glucuronidase activity during the F&V
      than the basal diet (ratio, F&V versus basal diet, 1.09; 95% CI, 1.05-1.13; P <
      0.01). These results were probably due to decreased beta-glucuronidase activity
      during the basal diet (ratio, basal period versus preintervention, 0.93; 95% CI,
      0.87-0.98; P = 0.01) rather than increased enzyme activity during the F&V diet
      (ratio, F&V period versus preintervention, 1.01; 95% CI, 0.96-1.06; P = 0.64).
      Response to the experimental diet did not differ by sex (P(interaction) = 0.30),
      but there was a suggestion of a short-term diet effect at 8 versus 15 days
      (P(interaction) = 0.06). CONCLUSION: This intervention of selected F&V did not
      lower beta-glucuronidase activity. Further investigation is needed regarding what
      other foods and phytochemicals may influence beta-glucuronidase activity and
      effect modifiers of this relation.

PMID- 18628436
TI  - Community-based mass ultrasonographic screening of hepatocellular carcinoma among
      thrombocytopenic adults.
AB  - Thrombocytopenia has been reported as a valid surrogate for liver cirrhosis and
      could be used to identify groups at high risk of hepatocellular carcinoma (HCC)
      for ultrasonographic (US) screening. We designed this two-stage community-based
      screening for HCC. In 2004, subjects (ages > or =40 years) were invited to
      undergo comprehensive health examinations, with 17,551 men (ages 63.0 +/- 11.5
      years) and 39,151 women (ages 59.9 +/- 11.7 years) participating. Subjects with
      platelet counts <150 x 10(9)/L or alpha-fetoprotein (AFP) >20 ng/mL were enrolled
      for the second-stage US screening; 3,242 subjects (5.7%; male/female,
      1,415/1,827; age 66 +/- 10 years) were candidates for US screening and 2,983
      (92.2%) responded. Of 137 suspected cases, 124 (90.5%) complied with referral for
      confirmation and 72 (58.1%) were confirmed to be HCC cases (male/female, 41/31;
      age 68.1 +/- 8.8 years). Screening with AFP, thrombocytopenia, or both could
      identify 0.64% (n = 364), 5.33% (n = 3,205), and 5.7% (n = 3,242) of the high
      risk subjects from the population, estimated to include 50.5%, 54.5%, and 71.3%
      of all HCC cases. Among confirmed patients, tumor diameters were <3 cm for the 27
      (37.5%) patients and 3 to 5 cm for the 23 (31.9%) patients. Only 5 (6.9%)
      patients' conditions were too advanced to be actively treated. This study
      enrolled only 5.7% of the participants for US, which cover 64.7% to 71.3% of the
      HCC cases. Most (93%) of the detected cases were caught early enough to undergo
      effective treatment modalities. This HCC screening protocol should be feasible,
      economical, and effective.

PMID- 18628437
TI  - Mathematical modeling of folate metabolism: predicted effects of genetic
      polymorphisms on mechanisms and biomarkers relevant to carcinogenesis.
AB  - Low-folate status and genetic polymorphisms in folate metabolism have been linked
      to several cancers. Possible biological mechanisms for this association include
      effects on purine and thymidine synthesis, DNA methylation, or homocysteine
      concentrations. The influence of genetic variation in folate metabolism on these
      putative mechanisms or biomarkers of cancer risk has been largely unexplored. We
      used a mathematical model that simulates folate metabolism biochemistry to
      predict (a) the effects of polymorphisms with defined effects on enzyme function
      (MTHFR and TS) and (b) the effects of potential, as-of-yet-unidentified
      polymorphisms in a comprehensive set of folate-metabolizing enzymes on biomarkers
      and mechanisms related to cancer risk. The model suggests that there is
      substantial robustness in the pathway. Our predictions were consistent with
      measured effects of known polymorphisms in MTHFR and TS on biomarkers.
      Polymorphisms that alter enzyme function of FTD, FTS, and MTCH are expected to
      affect purine synthesis, FTS more so under a low-folate status. In addition, MTCH
      polymorphisms are predicted to influence thymidine synthesis. Polymorphisms in
      methyltransferases should affect both methylation rates and thymidylate
      synthesis. Combinations of polymorphisms in MTHFR, TS, and SHMT are expected to
      affect nucleotide synthesis in a nonlinear fashion. These investigations provide
      information on effects of genetic polymorphisms on biomarkers, including those
      that cannot be measured well, and highlight robustness and sensitivity in this
      complex biological system with regard to genetic variability. Although the
      proportional changes in biomarkers of risk with individual polymorphisms are
      frequently small, they may be quite relevant if present over an individual's
      lifetime.

PMID- 18628438
TI  - IGF-I, IGFBP-3, and IGF-I/IGFBP-3 ratio: no association with incident colorectal
      cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

PMID- 18628439
TI  - No association between parental or subject occupation and brain tumor risk.

PMID- 18628440
TI  - No evidence for linkage with melanoma in Italian melanoma-prone families.

PMID- 18628442
TI  - Cyclin E overexpression relates to ovarian cancer histology but not to risk
      factors.

PMID- 18628443
TI  - Racial differences in sleep medication use: a cross-sectional study of the
      Johnston County Osteoarthritis Project.
AB  - BACKGROUND: Little is known about racial differences in the use of sleep
      medications. OBJECTIVES: To compare sleep medication use among African Americans
      and whites with self-reported current sleep problems. METHODS: Participants were
      1910 individuals (69% female, 34% African American, 66% white) from the Johnston
      County Osteoarthritis Project. We examined racial differences in self-reported
      current use of prescription, nonprescription, herbal, and other medications for
      sleep. Multivariable logistic regression models controlled for age, sex,
      education, health insurance, symptomatic hip or knee osteoarthritis, depressive
      symptoms, obesity, fair or poor general health, and self-reported annual days of
      sleep problems. Models were conducted separately for the whole sample and for men
      and women. RESULTS: Among participants with current sleep problems, 31% were
      using one or more types of sleep medication: 17% prescription, 12%
      nonprescription, 1% herbal, and 3% other products. African Americans were less
      likely than whites to be using any sleep medication (25% vs 35%; p < 0.001),
      prescription sleep medication (14% vs 19%; p = 0.003), and nonprescription sleep
      medication (10% vs 13%; p = 0.048). These racial differences persisted in
      multivariable models. In sex-stratified analyses, there were significant racial
      differences in sleep medication use only among women. CONCLUSIONS: African
      Americans were less likely than whites to report current use of prescription and
      nonprescription sleep medications; these results appeared to be largely driven by
      racial differences among women. Additional research should study possible
      underlying factors and determine whether these racial differences impact clinical
      outcomes.

PMID- 18628444
TI  - Acetaminophen overdose with altered acetaminophen pharmacokinetics and
      hepatotoxicity associated with premature cessation of intravenous N
      acetylcysteine therapy.
AB  - OBJECTIVE: To report a case of erratic absorption, double peak serum
      concentrations, and hepatotoxicity following premature cessation of intravenous N
      acetylcysteine (NAC) treatment in the setting of a massive acetaminophen
      overdose. CASE SUMMARY: A 78-year-old man reportedly ingested approximately 96
      immediate-release acetaminophen 500-mg tablets (48 g) over a one-hour period in
      an apparent suicide attempt. The acetaminophen concentration at 2.25 hours was
      264 microg/mL. Intravenous NAC was initiated 5 hours postingestion. At 6.25 hours
      postingestion, the acetaminophen concentration was 281 microg/mL. Following
      administration of intravenous NAC for 21 hours, therapy was discontinued despite
      a residual acetaminophen concentration of 116 microg/mL. The patient experienced
      hepatotoxicity, coagulopathy, and renal injury. Pharmacokinetic analysis revealed
      significantly prolonged acetaminophen absorption and a second peak acetaminophen
      concentration of 228 microg/mL approximately 48 hours postingestion. Direct in
      hospital monitoring of the patient made a second ingestion unlikely. DISCUSSION:
      Acetaminophen overdose is usually effectively managed with NAC. Patients with
      massive ingestions may have altered absorption kinetics due to acetaminophen's
      solubility being exceeded, physiologically or chemically altered gastrointestinal
      emptying or motility, or other factors. These patients may benefit from
      gastrointestinal decontamination and prolonged NAC therapy. CONCLUSIONS: In
      patients with massive acetaminophen ingestion, erratic absorption may occur, and
      toxic serum concentrations may persist beyond a standard 21-hour course of
      intravenous NAC therapy. Acetaminophen concentrations and aminotransferase levels
      should be evaluated at the completion of the intravenous NAC infusion to ensure
      complete elimination of acetaminophen and absence of hepatotoxicity and to
      exclude the need for prolonged treatment.

PMID- 18628445
TI  - Famciclovir-induced leukocytoclastic vasculitis.
AB  - OBJECTIVE: To report a case of famciclovir-induced leukocytoclastic vasculitis
      (LCV). CASE SUMMARY: A 67-year-old white female presented to the hospital for
      evaluation of large, bilateral palpable purpura; coalescing ulcers with central
      eschars; and small, red violaceous papules on her legs and groin. Approximately 2
      months prior to this hospitalization, the woman was diagnosed with shingles of
      her left T1-T2 nerve distribution and was treated with famciclovir 500 mg 3 times
      daily, which was her first exposure to this medication. Her shingles resolved;
      however, on day 4 of treatment, she began to notice red spots on both of her legs
      that began to progressively blister and increase in size. She discontinued
      famciclovir at that time. The rash persisted and spread to her abdomen, groin,
      legs, feet, and toes. She underwent punch biopsy that revealed LCV. Workup was
      negative for antinuclear antibody, rheumatoid factor, hepatitis B and C virus,
      perinuclear-staining antineutrophil cytoplasmic antibodies, cytoplasmic-staining
      antineutrophil cytoplasmic antibodies, antibodies to extractable nuclear
      antigens, proteinase 3, and myeloperoxidase. The patient improved with daily oral
      steroids and local wound care. DISCUSSION: LCV has been reported only once before
      in the English literature as of January 2008. The most common cause of LCV is
      medication use, but it is a diagnosis of exclusion. It is hypothesized that drugs
      act as haptens, which cause an immune response. An objective causality assessment
      using the Naranjo probability scale suggested that famciclovir was the probable
      cause of LCV in this patient. CONCLUSIONS: Healthcare professionals should be
      aware of the possible development of famciclovir-induced LCV.

PMID- 18628446
TI  - Association between selective serotonin-reuptake inhibitors, second-generation
      antipsychotics, and neuroleptic malignant syndrome.
AB  - OBJECTIVE: To review the published reports of neuroleptic malignant syndrome
      (NMS) associated with the use of selective serotonin-reuptake inhibitors (SSRIs)
      and second-generation antipsychotics. DATA SOURCE: Information was selected from
      a MEDLINE search of English-language literature (1950-May 2008). Manual search of
      all published cases indexed in MEDLINE (English language only) of NMS associated
      with second-generation antipsychotics was also performed. STUDY SELECTION AND
      DATA EXTRACTION: Pertinent information from all reports obtained was included,
      with specific emphasis on patient age, sex, second-generation antipsychotic
      involved, SSRI or other antidepressant involved, time of onset of NMS symptoms in
      relation to medication changes, treatment administered, and outcome of the
      reaction. DATA SYNTHESIS: NMS has been reported with every second-generation
      antipsychotic agent. It is unclear whether concomitant therapy with other agents
      may increase the risk of NMS development via pharmacodynamic or pharmacokinetic
      mechanisms or both. The suggested pharmacodynamic mechanism for increased risk of
      NMS with concomitant use of SSRIs is the effect of serotonin on dopamine release.
      Serotonin further inhibits dopamine release and thereby may worsen a
      hypodopaminergic state induced by antipsychotics. Pharmacokinetic factors may
      also play a role in some NMS cases involving an SSRI by increasing antipsychotic
      concentrations. An examination of case reports seems to indicate that at least in
      some cases, a temporal relationship exists with the addition of an SSRI to
      existing antipsychotic therapy. CONCLUSIONS: The use of SSRIs may be associated
      with an increased risk of NMS development in those receiving second-generation
      antipsychotics. Clinicians should closely monitor patients for the potential
      development of NMS.

PMID- 18628448
TI  - Randomized phase III clinical trial designs for targeted agents.
AB  - PURPOSE: Cancer therapies with mechanisms of action which are very different from
      the more conventional chemotherapies are now being developed. In this article, we
      investigate the performance of several phase III clinical trial designs, both for
      testing the overall efficacy of a targeted agent and for testing its efficacy in
      a subgroup of patients with a tumor marker present. We study different designs
      and different underlying scenarios assuming continuous markers, and assess the
      trade-off between the number of patients on the study and the effectiveness of
      treatment in the subgroup of marker-positive patients. EXPERIMENTAL DESIGN: We
      investigate binary outcomes and use simulation studies to determine sample size
      and power for the different designs and the various scenarios. We also simulate
      marker prevalence and marker misclassification and evaluate their effect on power
      and sample size. RESULTS: In general, a targeted design which randomizes patients
      with the appropriate marker status performs the best in all scenarios with an
      underlying true predictive marker. Randomizing all patients regardless of their
      marker values performs as well as or better in most cases than a clinical trial
      that randomizes the patient to a treatment strategy based on marker value versus
      standard of care. CONCLUSION: If there is the possibility that the new treatment
      helps marker-negative patients, or that the cutpoint determining marker status
      has not been well established and the marker prevalence is large enough, we
      recommend randomizing all patients regardless of marker values, but using a
      design such that both the overall and the targeted subgroup hypothesis can be
      tested.

PMID- 18628449
TI  - Multi-arm clinical trials of new agents: some design considerations.
AB  - A major challenge in the development of anticancer therapies is the considerable
      time and resources needed for conducting randomized clinical trials (RCT). There
      is a need for more efficient RCT designs that accelerate development, minimize
      costs, and make trials more appealing to patients. We review the statistical and
      logistical characteristics of multi-arm designs that compare several experimental
      treatments to a common control arm. In particular, we present a rationale for not
      requiring multiplicity adjustment in multi-arm trials that are designed for
      logistical efficiency. Relative to conducting separate RCTs for each experimental
      agent, this multi-arm design is shown to require a lower total sample size than
      multiple two-arm trials.

PMID- 18628450
TI  - RLIP76 and Cancer.
AB  - RLIP76 is a multifunctional membrane protein that transports glutathione
      conjugates of electrophilic compounds and other xenobiotics including
      chemotherapy agents out of cells. The protein is overexpressed in lung
      carcinomas, ovarian carcinomas, and melanomas. The protein also binds Ral and
      participates in mitotic spindle function, clathrin-dependent endocytosis, and
      triggers GTPase-activating protein activity. It is found throughout the cell, in
      membrane, cytosol, and the nucleus, and is known to shift between these
      compartments in response to stress. Loss of RLIP76 by antibody or antisense
      therapy is associated with increased sensitivity to radiation and chemotherapy.
      Conversely, liposomally delivered RLIP may treat poisoning and wounds.

PMID- 18628451
TI  - Ixabepilone in combination with capecitabine and as monotherapy for treatment of
      advanced breast cancer refractory to previous chemotherapies.
AB  - PURPOSE: To describe the considerations leading to marketing approval of
      ixabepilone in combination with capecitabine and as monotherapy for the treatment
      of advanced breast cancer that is refractory to other chemotherapies.
      EXPERIMENTAL DESIGN: Data from one randomized multicenter trial comparing
      combination therapy with ixabepilone and capecitabine to capecitabine alone were
      analyzed for support of the combination therapy indication. For monotherapy, a
      single-arm trial of ixabepilone was analyzed. Supporting data came from an
      additional single-arm combination therapy study and two single-arm monotherapy
      studies. RESULTS: In patients with metastatic or locally advanced breast cancer
      who had disease progression on or following an anthracycline and a taxane,
      ixabepilone plus capecitabine showed an improvement in progression-free survival
      compared with capecitabine alone {median progression-free survival, 5.7 [95%
      confidence interval (95% CI), 4.8-6.7] versus 4.1 (95% CI, 3.1-4.3) months,
      stratified log-rank P < 0.0001; hazard ratio, 0.69 (95% CI, 0.58-0.83)}. As
      monotherapy for patients who had disease progression on or following an
      anthracycline, a taxane, and capecitabine, ixabepilone as monotherapy showed a
      12% objective response rate by independent blinded review and 18% by investigator
      assessment. The major toxicities from ixabepilone therapy were peripheral
      neuropathy and myelosuppression, particularly neutropenia. CONCLUSIONS: On
      October 16, 2007, the Food and Drug Administration approved ixabepilone for
      injection in combination with capecitabine or as monotherapy for the treatment of
      patients with advanced breast cancer who have experienced disease progression on
      previous chemotherapies.

PMID- 18628452
TI  - Targeted therapies to improve tumor immunotherapy.
AB  - Durable tumor regression and potential cures of metastatic solid cancers can be
      achieved by a variety of cellular immunotherapy strategies, including cytokine
      therapy, dendritic cell-based vaccines, and immune-activating antibodies, when
      used in so-called immune-sensitive cancers such as melanoma and renal cell
      carcinoma. However, these immunotherapy strategies have very low tumor response
      rates, usually in the order of 5% to 10% of treated patients. We propose that the
      antitumor activity of adequately stimulated tumor antigen-specific T cells is
      limited by local factors within the tumor milieu and that pharmacologic
      modulation of this milieu may overcome tumor resistance to immunotherapy. By
      understanding the mechanisms of cancer cell immune escape, it may be possible to
      design rational combinatorial approaches of novel therapies able to target
      immunosuppressive or antiapoptotic molecules in an attempt to reverse resistance
      to immune system control. We term this mode of treatment "immunosensitization."
      Ideal candidates for immunosensitizing drugs would be targeted drugs that block
      key oncogenic mechanisms in cancer cells resulting in a proapoptotic cancer cell
      milieu and at the same time do not negatively interfere with critical lymphocyte
      functions.

PMID- 18628453
TI  - Therapeutic options against BCR-ABL1 T315I-positive chronic myelogenous leukemia.
AB  - Despite the efficacy of imatinib therapy in chronic myelogenous leukemia, the
      development of resistance continues to challenge the treatment of this disease.
      Mutations within the kinase domain of BCR-ABL1 constitute the most frequent
      mechanism of resistance in patients with chronic myelogenous leukemia treated
      with imatinib or the second generation tyrosine kinase inhibitors nilotinib and
      dasatinib. Of particular concern is the substitution of the threonine residue at
      the highly conserved gatekeeper residue 315 with a bulkier hydrophobic isoleucine
      amino acid. This mutation causes steric hindrance precluding the access ATP
      competitive inhibitors to the ATP-binding pocket. To expedite the identification
      of strategies to override the resistance imposed by the T315I mutation, several
      strategies have been pursued, including the exploitation of BCR-ABL1 kinase sites
      distant from the ATP-binding pocket to cripple the kinase activity of the enzyme
      and inhibiting signaling pathways downstream from BCR-ABL1. Recent insights
      gained regarding the structural biology of T315I have led to the development of a
      variety of compounds against this mutant. We herein summarize the most clinically
      promising anti-T315I therapies.

PMID- 18628454
TI  - Comparison of nomograms with other methods for predicting outcomes in prostate
      cancer: a critical analysis of the literature.
AB  - PURPOSE: Accurate estimates of risk are essential for physicians if they are to
      recommend a specific management to patients with prostate cancer. Accurate risk
      estimates are also required for clinical trial design, to ensure homogeneous
      patient groups. Because there is more than one model available for prediction of
      most outcomes, model comparisons are necessary for selection of the best model.
      We describe the criteria based on which to judge predictive tools, describe the
      limitations of current predictive tools, and compare the different predictive
      methodologies that have been used in the prostate cancer literature. EXPERIMENTAL
      DESIGN: Using MEDLINE, a literature search was done on prostate cancer decision
      aids from January 1966 to July 2007. RESULTS: The decision aids consist of
      nomograms, risk groupings, artificial neural networks, probability tables, and
      classification and regression tree analyses. The following considerations need to
      be applied when the qualities of predictive models are assessed: predictive
      accuracy (internal or ideally external validation), calibration (i.e.,
      performance according to risk level or in specific patient subgroups),
      generalizability (reproducibility and transportability), and level of complexity
      relative to established models, to assess whether the new model offers advantages
      relative to available alternatives. Studies comparing decision aids have shown
      that nomograms outperform the other methodologies. CONCLUSIONS: Nomograms provide
      superior individualized disease-related risk estimations that facilitate
      management-related decisions. Of currently available prediction tools, the
      nomograms have the highest accuracy and the best discriminating characteristics
      for predicting outcomes in prostate cancer patients.

PMID- 18628455
TI  - Function of JunB in transient amplifying cell senescence and progression of human
      prostate cancer.
AB  - PURPOSE: Replicative senescence in cells acts as a barrier against excessive
      proliferation and carcinogenesis. Transient amplifying cells (TAC) are a subset
      of basal cell populations within the prostate from which cancers are thought to
      originate; therefore, we focused on prostate TAC to investigate the molecular
      mechanisms by which the TAC may be able to evade senescence. EXPERIMENTAL DESIGN:
      TAC clones were isolated from each zone within the whole prostate and analyzed in
      flow cytometry. Prostate cancer cells were transfected with junB small
      interfering RNA (siRNA) and examined by chorioallantoic membrane assay for cancer
      invasion. Immunohistochemical analysis was done in primary and metastatic
      prostate cancer specimens. RESULTS: TAC populations showed increased expression
      of p53, p21, p16, and pRb, resulting in senescence. TAC clones with reduced p16
      expression successfully bypassed this phase. We further found close correlation
      between the levels of junB and p16 expression. Repeated transfection of junB
      siRNA in prostatic TAC allowed the cells to escape senescence presumably through
      inactivation of p16/pRb. The chorioallantoic membrane invasion assay showed much
      lower in invasive cancer cells with high expression of junB; conversely,
      silencing of junB by transfection with junB siRNA promoted invasion. We also
      found that metastatic prostate cancers, as well as cancers with high Gleason
      scores, showed significantly low junB immunopositivity. CONCLUSIONS: JunB is an
      essential upstream regulator of p16 and contributes to maintain cell senescence
      that blocks malignant transformation of TAC. JunB thus apparently plays an
      important role in controlling prostate carcinogenesis and may be a new target for
      cancer prevention and therapy.

PMID- 18628456
TI  - Anti-invasive and antimetastatic activities of ribosomal protein S6 kinase 4 in
      breast cancer cells.
AB  - PURPOSE: We have previously shown that p90 ribosomal protein S6 kinase 4 (RSK4),
      an X-linked gene, is highly up-regulated in mammary tumors of MMTV-c-Myc
      transgenic mice. In this study, we further investigated whether RSK4 inhibits or
      promotes breast tumor growth and progression. EXPERIMENTAL DESIGN: Stable
      overexpression or small interfering RNA-mediated knockdown of RSK4 was done in
      the MDA-MB-231 cell line. Stable clones were tested for cell proliferation,
      anchorage-independent growth in soft agar, invasive and metastatic ability of
      these clones in vitro and tumorigenesis, invasive and metastatic ability in vivo
      in severe combined immunodeficient mice. RESULTS: Here, we show that exogenous
      expression of RSK4 resulted in decreased cell proliferation and increased
      accumulation of cells in G(0)-G(1) phase, which paralleled with enhanced
      expression of tumor suppressor genes: retinoblastoma protein, retinobl astoma
      associated 46 kDa protein, and p21 protein. Overexpression of RSK4 resulted in
      reduced colony formation in soft agar and suppressed invasive and migratory
      activities of MDA-MB-231 cells both in vitro and in vivo. Importantly, RSK4
      overexpressing cells showed up-regulation of claudin-2 and down-regulation of
      CXCR4, both of these play roles in invasion and chemotaxis. CONCLUSIONS: These
      results indicate that RSK4 expression may limit the oncogenic, invasive, and
      metastatic potential of breast cancer cells. Anti-invasive and antimetastatic
      activities of RSK4 may be, in part, due to its regulation of claudin-2. Increased
      expression of RSK4 in c-Myc-overexpressing cells and a dose-dependent induction
      of luciferase reporter gene activity suggest that c-Myc may regulate RSK4
      expression.

PMID- 18628457
TI  - Transformation by oncogenic mutants and ligand-dependent activation of FLT3 wild
      type requires the tyrosine residues 589 and 591.
AB  - PURPOSE: Mutations in the receptor tyrosine kinase FLT3 are found in up to 30% of
      acute myelogenous leukemia patients and are associated with an inferior
      prognosis. In this study, we characterized critical tyrosine residues responsible
      for the transforming potential of active FLT3-receptor mutants and ligand
      dependent activation of FLT3-WT. EXPERIMENTAL DESIGN: We performed a detailed
      structure-function analysis of putative autophosphorylation tyrosine residues in
      the FLT3-D835Y tyrosine kinase domain (TKD) mutant. All tyrosine residues in the
      juxtamembrane domain (Y566, Y572, Y589, Y591, Y597, and Y599), interkinase domain
      (Y726 and Y768), and COOH-terminal domain (Y955 and Y969) of the FLT3-D835Y
      construct were successively mutated to phenylalanine and the transforming
      activity of these mutants was analyzed in interleukin-3-dependent Ba/F3 cells.
      Tyrosine residues critical for the transforming potential of FLT3-D835Y were also
      analyzed in FLT3 internal tandem duplication mutants (FLT3-ITD)and the FLT3 wild
      type (FLT3-WT) receptor. RESULT: The substitution of the tyrosine residues by
      phenylalanine in the juxtamembrane, interkinase, and COOH-terminal domains
      resulted in a complete loss of the transforming potential of FLT3-D835Y
      expressing cells which can be attributed to a significant reduction of signal
      tranducer and activator of transcription 5 (STAT5) phosphorylation at the
      molecular level. Reintroduction of single tyrosine residues revealed the critical
      role of Y589 and Y591 in reconstituting interleukin-3-independent growth of FLT3
      TKD-expressing cells. Combined mutation of Y589 and Y591 to phenylalanine also
      abrogated ligand-dependent proliferation of FLT3-WT and the transforming
      potential of FLT3-ITD-with a subsequent abrogation of STAT5 phosphorylation.
      CONCLUSION: We identified two tyrosine residues, Y589 and Y591, in the
      juxtamembrane domain that are critical for the ligand-dependent activation of
      FLT3-WT and the transforming potential of oncogenic FLT3 mutants.

PMID- 18628458
TI  - Genomic differences between pure ductal carcinoma in situ of the breast and that
      associated with invasive disease: a calibrated aCGH study.
AB  - PURPOSE: In the quest for new targets, genomes of ductal carcinoma in situ (DCIS)
      and infiltrating duct carcinoma (IDC) have been compared previously; however,
      genomic alterations associated with cancer progression were difficult to
      identify. We hypothesized that significant events can be detected by comparing
      lesions with a broader range of behavior: from pure DCIS to IDC associated with
      lymph node metastasis. EXPERIMENTAL DESIGN: Array comparative genomic
      hybridization, calibrated by self-self hybridization tests, was used to study 6
      cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread
      to the local lymph nodes. RESULTS: Pure DCIS exhibited a marginally higher degree
      of genomic complexity than DCIS and IDC components of invasive tumors. The latter
      two showed similarity between tumors and between components of the same tumor
      with several regions detected preferentially compared with pure DCIS. IDC
      associated with lymph node metastases showed similarity of genomic profiles as a
      group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC
      size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05).
      CONCLUSIONS: Our findings suggest that DCIS and IDC are associated with specific
      genomic events. DCIS associated with IDC is genomically similar to the invasive
      component and therefore may represent either a clone with high invasive potential
      or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2
      is a candidate region for further testing as a predictor of invasion when
      detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC.

PMID- 18628459
TI  - Expression of Aurora A (but not Aurora B) is predictive of survival in breast
      cancer.
AB  - PURPOSE: The cell cycle mediators Aurora A and B are targets of drugs currently
      in clinical development. As with other targeted therapies in breast cancer,
      response to therapy might be associated with target expression in tumors. We
      therefore assessed expression of Aurora A and B in breast tumors and studied
      associations with clinical/pathologic variables. EXPERIMENTAL DESIGN: Tissue
      microarrays containing primary specimens from 638 patients with 15-year follow-up
      were employed to assess expression of Aurora A and B using our automated
      quantitative analysis method; we used cytokeratin to define pixels as breast
      cancer (tumor mask) within the array spot and measured Aurora A and B expression
      within the mask using Cy5-conjugated antibodies. RESULTS: Aurora A and B
      expression was variable in primary breast tumors. High Aurora A expression was
      strongly associated with decreased survival (P = 0.0005). On multivariable
      analysis, it remained an independent prognostic marker. High Aurora A expression
      was associated with high nuclear grade and high HER-2/neu and progesterone
      receptor expression. Aurora B expression was not associated with survival.
      CONCLUSIONS: Aurora A expression defines a population of patients with decreased
      survival, whereas Aurora B expression does not, suggesting that Aurora A might be
      the preferred drug target in breast cancer. Aurora A expression in early-stage
      breast cancer may identify a subset of patients requiring more aggressive or
      pathway-targeted treatment. Prospective studies are needed to confirm the
      prognostic role of Aurora A as well as the predictive role of Aurora A expression
      in patients treated with Aurora A inhibitors.

PMID- 18628460
TI  - Analysis and reproducibility of 3'-Deoxy-3'-[18F]fluorothymidine positron
      emission tomography imaging in patients with non-small cell lung cancer.
AB  - PURPOSE: Imaging tumor proliferation with 3'-deoxy-3'-[(18)F]fluorothymidine
      (FLT) and positron emission tomography is being developed with the goal of
      monitoring antineoplastic therapy. This study assessed the methods to measure FLT
      retention in patients with non-small cell lung cancer (NSCLC) to measure the
      reproducibility of this approach. EXPERIMENTAL DESIGN: Nine patients with NSCLC
      who were untreated or had progressed after previous therapy were imaged twice
      using FLT and positron emission tomography within 2 to 7 days. Reproducibility
      (that is, error) was measured as the percent difference between the two patient
      scans. Dynamic imaging was obtained during the first 60 min after injection.
      Activity in the blood was assessed from aortic images and the fraction of
      unmetabolized FLT was measured. Regions of interest were drawn on the plane with
      the highest activity and the adjacent planes to measure standardized uptake value
      (SUV(mean)) and kinetic variables of FLT flux. RESULTS: We found that the
      SUV(mean) obtained from 30 to 60 min had a mean error of 3.6% (range, 0.6-6.9%;
      SD, 2.3%) and the first and second scans were highly correlated (r(2) = 0.99; P <
      0.0001). Using shorter imaging times from 25 to 30 min or from 55 to 60 min
      postinjection also resulted in small error rates; SUV(mean) mean errors were 8.4%
      and 5.7%, respectively. Compartmental and graphical kinetic analyses were also
      fairly reproducible (r(2) = 0.59; P = 0.0152 and r(2) = 0.58; P = 0.0175
      respectively). CONCLUSION: FLT imaging of patients with NSCLC was quite
      reproducible with a worst case SUV(mean) error of 21% when using a short imaging
      time.

PMID- 18628461
TI  - Visualization of circulating melanoma cells in peripheral blood of patients with
      primary uveal melanoma.
AB  - PURPOSE: In patients with uveal melanoma, tumor cell dissemination and subsequent
      formation of metastases are confined mainly to the hematogenous route. Here, we
      sought to isolate circulating melanoma cells in peripheral blood of patients with
      primary uveal melanoma and clinically localized disease. EXPERIMENTAL DESIGN:
      Blood samples from 52 patients with clinically localized uveal melanoma and from
      20 control individuals were prospectively collected before therapy of the primary
      tumor. Tumor cells expressing the melanoma-associated chondroitin sulfate
      proteoglycan were enriched by immunomagnetic cell sorting and visualized by
      immunocytologic staining. Results were compared with clinical data at
      presentation. RESULTS: In 10 of 52 patients [19%; 95% confidence interval (95%
      CI), 10-33%], between 1 and 5 circulating melanoma cells were detected in 50 mL
      peripheral blood. No melanoma-associated chondroitin sulfate proteoglycan
      positive cells were detected in any of the 20 controls examined. The presence of
      tumor cells in peripheral blood was associated with ciliary body invasion [odds
      ratio (OR), 20.0; 95% CI, 3.0-131.7], advanced local tumor stage (OR, 6.7; 95%
      CI, 1.8-25.4), and anterior tumor localization (OR, 4.0; 95% CI, 1.2-12.7), all
      established factors for uveal melanoma progression. CONCLUSIONS: Immunomagnetic
      enrichment enables detection of intact melanoma cells in peripheral blood of
      patients with clinically localized ocular disease. Visualization and capturing of
      these cells provide a unique tool for characterizing potentially metastasizing
      tumor cells from a primary melanoma at an early stage of the disease.

PMID- 18628462
TI  - Irradiance-dependent photobleaching and pain in delta-aminolevulinic acid
      photodynamic therapy of superficial basal cell carcinomas.
AB  - PURPOSE: In superficial basal cell carcinomas treated with photodynamic therapy
      with topical delta-aminolevulinic acid, we examined effects of light irradiance
      on photodynamic efficiency and pain. The rate of singlet-oxygen production
      depends on the product of irradiance and photosensitizer and oxygen
      concentrations. High irradiance and/or photosensitizer levels cause inefficient
      treatment from oxygen depletion in preclinical models. EXPERIMENTAL DESIGN: Self
      sensitized photobleaching of protoporphyrin IX (PpIX) fluorescence was used as a
      surrogate metric for photodynamic dose. We developed instrumentation measuring
      fluorescence and reflectance from lesions and margins during treatment at 633 nm
      with various irradiances. When PpIX was 90% bleached, irradiance was increased to
      150 mW/cm(2) until 200 J/cm(2) were delivered. Pain was monitored. RESULTS: In 33
      superficial basal cell carcinomas in 26 patients, photobleaching efficiency
      decreased with increasing irradiance above 20 mW/cm(2), consistent with oxygen
      depletion. Fluences bleaching PpIX fluorescence 80% (D80) were 5.7 +/- 1.6, 4.5
      +/- 0.3, 7.5 +/- 0.8, 7.4 +/- 0.3, 12.4 +/- 0.3, and 28.7 +/- 7.1 J/cm(2),
      respectively, at 10, 20, 40, 50, 60 and 150 mW/cm(2). At 20-150 mW/cm(2), D80
      doses required 2.5-3.5 min; times for the total 200 J/cm(2) were 22.2-25.3 min.
      No significant pain occurred up to 50 mW/cm(2); pain was not significant when
      irradiance then increased. Clinical responses were comparable to continuous 150
      mW/cm(2) treatment. CONCLUSIONS: Photodynamic therapy with topical delta
      aminolevulinic acid using approximately 40 mW/cm(2) at 633 nm is photodynamically
      efficient with minimum pain. Once PpIX is largely photobleached, higher
      irradiances allow efficient, rapid delivery of additional light. Optimal fluence
      at a single low irradiance is yet to be determined.

PMID- 18628463
TI  - A phase I and pharmacokinetic study of lapatinib in combination with letrozole in
      patients with advanced cancer.
AB  - PURPOSE: The main objectives of this phase I and pharmacokinetic, open-label
      study were to determine the optimally tolerated regimen (OTR), safety,
      pharmacokinetics, and clinical activity of lapatinib in combination with
      letrozole in patients with advanced solid malignancies. EXPERIMENTAL DESIGN:
      Patients with advanced breast cancer with immunohistochemically detectable
      estrogen or progesterone receptors or other cancers were eligible. Doses of
      lapatinib were escalated in cohorts of three subjects from 1,250 to a maximum of
      1,500 mg/d based on dose-limiting toxicities in the first treatment cycle. The
      letrozole dose was fixed at 2.5 mg/d. Additional patients were enrolled at the
      OTR dose level to further evaluate safety and for pharmacokinetic analyses.
      RESULTS: Thirty-nine patients were enrolled in the study: 12 in the dose
      escalation group, 7 in the OTR safety group, and 20 in the pharmacokinetic group.
      The OTR dose level was identified as 1,500 mg/d lapatinib and 2.5 mg/d letrozole.
      The most common (>25% of patients) drug-related adverse events were diarrhea
      (77%), rash (62%), nausea (46%), and fatigue (26%). No significant differences
      were observed in the pharmacokinetic variables (C(max) and AUC) of lapatinib and
      letrozole when coadministered compared with single-agent administration. One
      patient with endometrial cancer had a confirmed partial response. CONCLUSIONS:
      Clinically relevant doses of lapatinib in combination with letrozole were well
      tolerated and did not result in a pharmacokinetic interaction, and clinical
      antitumor activity was observed.

PMID- 18628464
TI  - Phase II trial of curcumin in patients with advanced pancreatic cancer.
AB  - PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and
      Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce
      objective responses in <10% of patients. We evaluated the clinical biological
      effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with
      potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against
      advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin
      by mouth daily until disease progression, with restaging every 2 months. Serum
      cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor
      antagonists and peripheral blood mononuclear cell expression of NF-kappaB and
      cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled,
      with 21 evaluable for response. Circulating curcumin was detectable as drug in
      glucuronide and sulfate conjugate forms, albeit at low steady-state levels,
      suggesting poor oral bioavailability. Two patients showed clinical biological
      activity. One had ongoing stable disease for >18 months; interestingly, one
      additional patient had a brief, but marked, tumor regression (73%) accompanied by
      significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL
      10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down
      regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal
      transducer and activator of transcription 3 in peripheral blood mononuclear cells
      from patients (most of whom had baseline levels considerably higher than those
      found in healthy volunteers). Whereas there was considerable interpatient
      variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and
      remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin
      is well tolerated and, despite its limited absorption, has biological activity in
      some patients with pancreatic cancer.

PMID- 18628465
TI  - Histone deacetylase inhibitor panobinostat induces clinical responses with
      associated alterations in gene expression profiles in cutaneous T-cell lymphoma.
AB  - PURPOSE: Histone deacetylase inhibitors can alter gene expression and mediate
      diverse antitumor activities. Herein, we report the safety and activity of the
      histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma
      (CTCL) and identify genes commonly regulated by panobinostat. EXPERIMENTAL
      DESIGN: Panobinostat was administered orally to patients with CTCL on Monday,
      Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was
      considered excessively toxic, and subsequent patients were treated at the
      expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4,
      8, and 24 h after administration were subjected to microarray gene expression
      profiling and real-time quantitative PCR of selected genes. RESULTS: Patients
      attained a complete response (n = 2), attained a partial response (n = 4),
      achieved stable disease with ongoing improvement (n = 1), and progressed on
      treatment (n = 2). Microarray data showed distinct gene expression response
      profiles over time following panobinostat treatment, with the majority of genes
      being repressed. Twenty-three genes were commonly regulated by panobinostat in
      all patients tested. CONCLUSIONS: Panobinostat is well tolerated and induces
      clinical responses in CTCL patients. Microarray analyses of tumor samples
      indicate that panobinostat induces rapid changes in gene expression, and
      surprisingly more genes are repressed than are activated. A unique set of genes
      that can mediate biological responses such as apoptosis, immune regulation, and
      angiogenesis were commonly regulated in response to panobinostat. These genes are
      potential molecular biomarkers for panobinostat activity and are strong
      candidates for the future assessment of their functional role(s) in mediating the
      antitumor responses of panobinostat.

PMID- 18628466
TI  - Class III beta-tubulin isotype predicts response in advanced breast cancer
      patients randomly treated either with single-agent doxorubicin or docetaxel.
AB  - PURPOSE: To evaluate the role of microtubule-associated variables as potential
      predictors of response and clinical outcome in patients with advanced breast
      cancer receiving single-agent docetaxel or doxorubicin chemotherapy. EXPERIMENTAL
      DESIGN: The analysis was done on 173 tumor samples from patients with locally
      advanced or metastatic breast cancer who have participated in the TAX-303 phase
      III trial in which patients were randomly assigned to receive docetaxel or
      doxorubicin. Expression of total alpha- and beta-tubulin, classes II to IV beta
      tubulin isotypes, and tau protein was evaluated by immunohistochemistry on
      formalin-fixed, paraffin-embedded tumors from the primary breast cancer. RESULTS:
      We observed that patients with "high" expression of class III beta-tubulin
      isotype had a higher probability of response to docetaxel than to doxorubicin
      treatment (odds ratio, 1.9; 95% confidence interval, 1.01-3.7; P = 0.05). No
      difference was observed in terms of time to progression or in terms of overall
      survival. CONCLUSIONS: This study suggests that the superiority of docetaxel over
      doxorubicin seems to be confined to the subgroup of patients with "high"
      expression of class III beta-tubulin isotype.

PMID- 18628467
TI  - Analysis of overall survival in patients with nonmetastatic castration-resistant
      prostate cancer treated with vaccine, nilutamide, and combination therapy.
AB  - PURPOSE: We reported previously the first randomized study of any kind in
      patients with nonmetastatic, castrate-resistant prostate cancer. The study
      employed vaccine, the hormone nilutamide, and the combined therapy (crossover for
      each arm) with an endpoint of time to progression. We now report survival
      analyses at 6.5 years from the initiation of therapy with a median potential
      follow-up of 4.4 years. EXPERIMENTAL DESIGN: Forty-two patients were randomized
      to receive either a poxvirus-based prostate-specific antigen (PSA) vaccine or
      nilutamide. Patients in either arm who developed increasing PSA without
      radiographic evidence of metastasis could cross over to receive the combined
      therapies. RESULTS: Median survival among all patients was 4.4 years from date of
      enrollment. Median survival exhibited a trend toward improvement for patients
      initially randomized to the vaccine arm (median, 5.1 versus 3.4 years; P = 0.13).
      Starting from the on-study date, the retrospectively determined subset of 12
      patients who initially received vaccine and then later received nilutamide
      suggested improved survival compared with the 8 patients who began with
      nilutamide and subsequently were treated with vaccine (median, 6.2 versus 3.7
      years; P = 0.045). A subgroup analysis of patients randomized to the vaccine arm
      versus the nilutamide arm showed substantial improvements in survival if at
      baseline patients had a Gleason score <7 (P = 0.033) and PSA <20 ng/dL (P =
      0.013) or who had prior radiation therapy (P = 0.018). CONCLUSIONS: These data
      indicate that patients with nonmetastatic castration-resistant prostate cancer
      (D0.5) who receive vaccine before second-line hormone therapy may potentially
      result in improved survival compared with patients who received hormone therapy
      and then vaccine. These data also suggest that patients with more indolent
      disease may derive greater clinical benefit from vaccine alone or vaccine before
      second-line hormone therapy compared with hormone therapy alone or hormone
      therapy followed by vaccine. These findings have potential implications for both
      the design and endpoint analysis of larger vaccine combination therapy trials.

PMID- 18628468
TI  - Local administration of PF-3512676 CpG-B instigates tumor-specific CD8+ T-cell
      reactivity in melanoma patients.
AB  - PURPOSE: Impaired immune effector functions in the melanoma sentinel lymph node
      (SLN) may allow for early metastatic events. Local administration of PF-3512676
      (formerly known as CpG 7909) has shown immunostimulatory effects of both
      dendritic cell and T-cell subsets in the melanoma SLN. Here, we set out to
      ascertain whether these PF-3512676-induced immunostimulatory effects translate
      into higher frequencies of melanoma-specific CD8(+) T cells. EXPERIMENTAL DESIGN:
      Twenty-four stage I to III melanoma patients were randomized to preoperative
      local administration of either PF-3512676 or saline. CD8(+) T cells from SLN and
      peripheral blood were tested for reactivity by IFN-gamma ELISPOT assay against
      several HLA-A1/A2/A3-restricted epitopes derived from various melanoma-associated
      antigens (MAA) in 21 of 24 enrolled patients. Frequencies of natural killer (NK)
      cells and frequencies and maturation state of dendritic cell subsets in the SLN
      were determined by flow cytometry. RESULTS: Melanoma-specific CD8(+) T-cell
      response rates against >1 MAA epitope in the SLN were 0 of 11 for the saline
      group versus 5 of 10 for the PF-3512676-administered group (P = 0.012). Of these
      5 responding patients, 4 also had a measurable response to >1 MAA epitope in the
      blood. Increased frequencies in the SLN of both MAA-specific CD8(+) T cells and
      NK cells correlated to CpG-induced plasmacytoid dendritic cell maturation.
      CONCLUSIONS: These data show an increase in melanoma-specific CD8(+) T-cell
      frequencies as well as an increased effector NK cell rate after a single dose of
      PF-3512676 and thus support the utility of local PF-3512676 administration as
      adjuvant treatment in early-stage melanoma to try and halt metastatic spread.

PMID- 18628469
TI  - ABCB1 genetic variation influences the toxicity and clinical outcome of patients
      with androgen-independent prostate cancer treated with docetaxel.
AB  - PURPOSE: Polymorphisms that are associated with ABCB1 expression and function may
      be linked to treatment efficacy and the development of neutropenia and
      neurotoxicity in patients with androgen-independent prostate cancer receiving
      docetaxel. EXPERIMENTAL DESIGN: Patients with androgen-independent prostate
      cancer treated with docetaxel alone (n = 23) or docetaxel and thalidomide (n =
      50) were genotyped for the ABCB1 1236C>T, 2677 G>T/A, and 3435 C>T alleles by
      direct sequencing, and diplotypes were constructed using an EM algorithm. The
      data were then compared with duration to onset of peripheral neuropathy,
      neutropenia grade, and survival after docetaxel. RESULTS: For patients receiving
      docetaxel alone, individuals carrying a diplotype consisting of the 1236C-2677G
      3435C linked alleles had improved overall survival after treatment (P = 0.0017).
      Additionally, patients treated with docetaxel and thalidomide carrying a
      diplotype consisting of the 2677T-3435T haplotype had a shorter median survival
      (P = 0.045). After adjusting for a particular set of polymorphisms and diplotype
      groupings, a hazard ratio of 10.87 was found for patients carrying the 2677GG
      genotype versus patients carrying other genotypes (P = 0.0048) in the docetaxel
      and thalidomide cohort. Among both treatment arms together, individuals carrying
      the 2677GG genotype also had a significantly longer time to neuropathy (P =
      0.035). Finally, there was a strong trend toward patients carrying the 2677TT
      3435TT diplotype having higher grades of neutropenia (P = 0.053). CONCLUSION: The
      data suggest that docetaxel-induced neuropathy, neutropenia grade, and overall
      survival could be linked to ABCB1 allelic variants with ensuing negative
      implications for docetaxel treatment in patients carrying ABCB1 variant
      genotypes.

PMID- 18628470
TI  - Therapeutic consequences from molecular biology for gastrointestinal stromal
      tumor patients affected by neurofibromatosis type 1.
AB  - PURPOSE: Patients affected by neurofibromatosis type 1 (NF-1) have an increased
      risk of developing gastrointestinal stromal tumors (GIST). NF-1-associated GISTs
      are usually wild type for c-KIT and platelet-derived growth factor receptor-alpha
      (PDGFR-alpha) mutations and harbor a different oncogenic molecular mechanism. The
      lack of data on imatinib activity raises the question whether to enroll these
      patients in clinical trials. We analyzed a large series of NF-1 related GISTs to
      discuss the therapeutic implications. MATERIALS AND METHODS: Clinical, pathologic
      (IHC to CD34, S100, bcl-2, PDGFRA), and molecular features (exons 9, 11, 13, 14,
      17 in c-kit and exons 12, 14, 18 in PDGFRA) of 28 patients were analyzed.
      RESULTS: The most common site of primary lesions was the small bowel (75%).
      Twelve patients (43%) had multiple tumors. Most tumors belonged to the high
      (30.5%) or intermediate risk group for malignant behavior (39%). Three patients
      developed peritoneal and liver metastases; another four had peritoneal spread
      only. All tumors were immunohistochemically strongly positive for CD117. Three
      primary KIT/PDGFRA activating mutations were found. Three metastatic patients
      treated with imatinib experienced progression, and only one had temporary stable
      disease. Median survival after starting treatment with imatinib was 21 months.
      CONCLUSIONS: This study is the largest series available and confirms that
      KIT/PDGFRA mutations in NF-1-associated GISTs are sporadic. Prognosis of
      metastatic tumors is poor, and imatinib response rate is low. Patients with NF-1
      GIST of high or intermediate risk should not be eligible for adjuvant trials of
      imatinib. Imatinib should not be used in a neoadjuvant intent in these patients,
      and molecular analysis of activating mutations is strongly recommended.

PMID- 18628471
TI  - Prevention and treatment of experimental estrogen receptor-negative mammary
      carcinogenesis by the synthetic triterpenoid CDDO-methyl Ester and the rexinoid
      LG100268.
AB  - PURPOSE: To test whether the triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien
      28-oic acid methyl ester (CDDO-Me) and the rexinoid LG100268 (268) prevent the
      formation of estrogen receptor (ER)-negative mammary tumors or either arrest the
      growth or cause regression of established tumors in MMTV-neu mice. EXPERIMENTAL
      DESIGN: For prevention, mice were fed control diet, CDDO-Me (60 mg/kg diet), 268
      (20 mg/kg diet), or the combination for 45 weeks. For treatment, mice with
      established tumors at least 4 mm in diameter were fed control diet, CDDO-Me (100
      mg/kg diet), 268 (60 mg/kg diet), or the combination for 4 weeks. RESULTS: CDDO
      Me and 268 significantly delayed the development of ER-negative tumors, with a 14
      and 24-week delay, respectively, compared with the control group for the time
      required to reach 50% tumor incidence. The combination of CDDO-Me and 268 was
      significantly more potent than the individual drugs, as only one tumor was found
      in the combination group, after 45 weeks on diet, at which time all control
      animals had tumors. Treating established tumors with CDDO-Me arrested the growth
      of 86% of the tumors, and 268 induced tumor regression in 85% of tumors. CDDO-Me
      and 268 target different signaling pathways and cell types. CDDO-Me inhibited
      constitutive STAT3 phosphorylation and the degradation of IKBalpha in ER-negative
      breast cancer cells, whereas 268 blocked IKBalpha degradation and the release of
      interleukin-6 in RAW264.7 macrophage-like cells, inhibited the ability of
      endothelial cells to organize into networks, and blocked angiogenesis in vivo.
      CONCLUSIONS: CDDO-Me and 268 are useful as individual drugs to prevent ER
      negative mammary tumorigenesis and to treat established tumors. They synergize
      when used in combination for prevention.

PMID- 18628472
TI  - Molecular characterization of the pediatric preclinical testing panel.
AB  - PURPOSE: Identifying novel therapeutic agents for the treatment of childhood
      cancers requires preclinical models that recapitulate the molecular
      characteristics of their respective clinical histotypes. EXPERIMENTAL DESIGN AND
      RESULTS: Here, we have applied Affymetrix HG-U133Plus2 profiling to an expanded
      panel of models in the Pediatric Preclinical Testing Program. Profiling led to
      exclusion of two tumor lines that were of mouse origin and five osteosarcoma
      lines that did not cluster with human or xenograft osteosarcoma samples. We
      compared expression profiles of the remaining 87 models with profiles from 112
      clinical samples representing the same histologies and show that model tumors
      cluster with the appropriate clinical histotype, once "immunosurveillance" genes
      (contributed by infiltrating immune cells in clinical samples) are eliminated
      from the analysis. Analysis of copy number alterations using the Affymetrix 100K
      single nucleotide polymorphism GeneChip showed that the models have similar copy
      number alterations to their clinical counterparts. Several consistent copy number
      changes not reported previously were found (e.g., gain at 22q11.21 that was
      observed in 5 of 7 glioblastoma samples, loss at 16q22.3 that was observed in 5
      of 9 Ewing's sarcoma and 4 of 12 rhabdomyosarcoma models, and amplification of
      21q22.3 that was observed in 5 of 7 osteosarcoma models). We then asked whether
      changes in copy number were reflected by coordinate changes in gene expression.
      We identified 493 copy number-altered genes that are nonrandom and appear to
      identify histotype-specific programs of genetic alterations. CONCLUSIONS: These
      data indicate that the preclinical models accurately recapitulate expression
      profiles and genetic alterations common to childhood cancer, supporting their
      value in drug development.

PMID- 18628473
TI  - Effective immunoconjugate therapy in cancer models targeting a serine protease of
      tumor fibroblasts.
AB  - PURPOSE: Invasion and metastasis of malignant epithelial cells into normal
      tissues is accompanied by adaptive changes in the mesenchyme-derived supporting
      stroma of the target organs. Altered gene expression in these nontransformed
      stromal cells provides potential targets for therapy. The present study was
      undertaken to determine the antitumor effects of an antibody-conjugate against
      fibroblast activation protein-alpha, a cell surface protease of activated tumor
      fibroblasts. EXPERIMENTAL DESIGN: A novel antibody-maytansinoid conjugate,
      monoclonal antibody (mAb) FAP5-DM1, was developed to target a shared epitope of
      human, mouse, and cynomolgus monkey fibroblast activation protein-alpha, enabling
      preclinical efficacy and tolerability assessments. We have used stroma-rich
      models in immunodeficient mice, which recapitulate the histotypic arrangement
      found in human epithelial cancers. RESULTS: Treatment with mAb FAP5-DM1 induced
      long-lasting inhibition of tumor growth and complete regressions in xenograft
      models of lung, pancreas, and head and neck cancers with no signs of
      intolerability. Analysis of chemically distinct conjugates, resistance models,
      and biomarkers implicates a unique mode of action, with mitotic arrest and
      apoptosis of malignant epithelial cells coupled to disruption of fibroblastic and
      vascular structures. CONCLUSIONS: We show that mAb FAP5-DM1 combines excellent
      efficacy and tolerability and provides a first assessment of the mode of action
      of a novel drug candidate for tumor stroma targeting, thus encouraging further
      development toward clinical testing of this treatment paradigm.

PMID- 18628474
TI  - KML001 cytotoxic activity is associated with its binding to telomeric sequences
      and telomere erosion in prostate cancer cells.
AB  - PURPOSE: KML001 (sodium metaarsenite) is an orally bioavailable arsenic compound
      that has entered phase I/II clinical trials in prostate cancer. In this study, we
      elucidated the mode of action of KML001 and investigated its effects on
      telomerase and telomeres. EXPERIMENTAL DESIGN: We compared telomere length to
      KML001 cytotoxic activity in a panel of human solid tumor cell lines. Duration of
      exposure and concentrations of KML001 that affect telomerase and telomeres were
      evaluated in relation to established mechanisms of arsenite action such as
      reactive oxygen species-related DNA damage induction. Binding of KML001 to
      telomeres was assessed by matrix-assisted laser desorption/ionization mass
      spectrometry. RESULTS: We established a significant inverse correlation (r(2) =
      0.9) between telomere length and cytotoxicity. KML001 exhibited activity in tumor
      cells with short telomeres at concentrations that can be achieved in serum of
      patients. We found that telomerase is not directly inhibited by KML001. Instead,
      KML001 specifically binds to telomeric sequences at a ratio of one molecule per
      three TTAGGG repeats leading to translocation of the telomerase catalytic subunit
      into the cytoplasm. In prostate cancer cells with short telomeres, KML001 caused
      telomere-associated DNA damage signaling as shown by gamma-H2AX induction and
      chromatin immunoprecipitation assays as well as a rapid telomere erosion shown by
      metaphase fluorescence in situ hybridization. These effects were not seen in a
      lung cancer cell line with long telomeres. Importantly, arsenification of
      telomeres preceded DNA lesions caused by reactive oxygen species production.
      CONCLUSIONS: Sodium metaarsenite is a telomere targeting agent and should be
      explored for the treatment of tumors with short telomeres.

PMID- 18628475
TI  - Paclitaxel encapsulated in cationic liposomes increases tumor microvessel
      leakiness and improves therapeutic efficacy in combination with Cisplatin.
AB  - PURPOSE: Paclitaxel encapsulated in cationic liposomes (EndoTAG-1) is a vascular
      targeting formulation for the treatment of solid tumors. It triggers intratumoral
      microthrombosis, causing significant inhibition of tumor perfusion and tumor
      growth associated with endothelial cell apoptosis. Here, we quantified the
      effects of repeated EndoTAG-1 therapy on tumor microvascular leakiness with
      respect to leukocyte-endothelial cell interactions, the targeting property of
      cationic liposomes, and the therapeutic combination with conventional cisplatin
      chemotherapy. EXPERIMENTAL DESIGN: Using dorsal skinfold chamber preparations in
      Syrian Golden hamsters, in vivo fluorescence microscopy experiments were done
      after repeated EndoTAG-1 treatment of A-Mel-3 tumors. Controls received glucose,
      paclitaxel alone, or cationic liposomes devoid of paclitaxel. Extravasation of
      rhodamine-labeled albumin was measured to calculate microvessel permeability, and
      intratumoral leukocyte-endothelial cell interactions were quantified.
      Subcutaneous tumor growth was evaluated after combination therapy followed by
      histologic analysis. RESULTS: Microvascular permeability was significantly
      increased only after treatment with EndoTAG-1, whereas intratumoral leukocyte
      endothelial cell interactions were not affected by any treatment. In separate
      skinfold chamber experiments, fluorescently labeled cationic liposomes kept their
      targeting property for tumor endothelial cells after repeated EndoTAG-1 treatment
      and no signs of extravasation were observed. Subcutaneous A-Mel-3 tumor growth
      was significantly inhibited by the combination of cisplatin and EndoTAG-1.
      CONCLUSIONS: These data show that vascular targeting with EndoTAG-1 increases
      tumor microvessel leakiness probably due to vascular damage. This mechanism is
      not mediated by inflammatory leukocyte-endothelial cell interactions.
      Manipulating the blood-tumor barrier by repeated tumor microvessel targeting
      using EndoTAG-1 can effectively be combined with tumor cell-directed conventional
      cisplatin chemotherapy.

PMID- 18628476
TI  - A novel recombinant soluble splice variant of Met is a potent antagonist of the
      hepatocyte growth factor/scatter factor-Met pathway.
AB  - PURPOSE: The Met receptor tyrosine kinase and its ligand, hepatocyte growth
      factor/scatter factor (HGF/SF), are involved in a wide range of biological
      activities, including cell proliferation, motility, invasion, and angiogenesis.
      The HGF/SF-Met signaling pathway is frequently activated in a variety of cancers,
      and uncontrolled Met activation correlates with highly invasive tumors and poor
      prognosis. In this study, we investigated the inhibitory effect of a novel
      soluble splice variant of Met on the HGF/SF-Met pathway. EXPERIMENTAL DESIGN:
      Using our alternative splicing modeling platform LEADS, we have identified a
      novel splice variant of the Met receptor, which encodes a truncated soluble form
      of the receptor. This variant was produced as a recombinant Fc-fused protein
      named Cgen-241A and was tested in various cell-based assays representing
      different outcomes of the HGF/SF-Met pathway. RESULTS: Cgen-241A significantly
      inhibited HGF/SF-induced Met phosphorylation as well as cell proliferation and
      survival. In addition, Cgen-241A showed a profound inhibitory effect on cell
      scattering, invasion, and urokinase up-regulation. The inhibitory effects of Cgen
      241A were shown in multiple human and nonhuman cell types, representing different
      modes of Met activation. Furthermore, Cgen-241A showed direct binding to HGF/SF.
      CONCLUSIONS: Taken together, our results indicate that Cgen-241A is a potent
      antagonist of the HGF/SF-Met pathway, underlining its potential as a therapeutic
      agent for the treatment of a wide variety of human malignancies that are
      dependent on this pathway.

PMID- 18628477
TI  - Slug (SNAI2) down-regulation by RNA interference facilitates apoptosis and
      inhibits invasive growth in neuroblastoma preclinical models.
AB  - PURPOSE: We assessed the relevance of Slug (SNAI2) for apoptosis resistance and
      invasion potential of neuroblastoma cells in vitro and in vivo. EXPERIMENTAL
      DESIGN: We evaluated the effect of imatinib mesylate on invasion and analyzed the
      genes modulated by imatinib mesylate treatment in neuroblastoma cells. Slug
      expression, inhibited by imatinib mesylate treatment, was knocked down in
      neuroblastoma cells by RNA interference, and the effects on invasion and
      apoptosis were evaluated in vitro. A pseudometastatic model of neuroblastoma in
      severe combined immunodeficient mice was used to assess the effects of Slug
      silencing alone or in combination with imatinib mesylate treatment on metastasis
      development. RESULTS: Microarray analysis revealed that several genes, including
      Slug, were down-regulated by imatinib mesylate. Slug expression was detectable in
      8 of 10 human neuroblastoma cell lines. Two Slug-expressing cell lines were
      infected with a vector encoding a microRNA to Slug mRNA. Infected cells with
      reduced levels of Slug were tested for the expression of apoptosis-related genes
      (p53, Bax, and Bcl-2) identified previously as Slug targets. Bcl-2 was down
      regulated in Slug-interfered cells. Slug down-regulation increased sensitivity to
      apoptosis induced by imatinib mesylate, etoposide, or doxorubicin. Invasion of
      Slug-silenced cells was reduced in vitro. Animals injected with Slug-silenced
      cells had fewer tumors than controls and the inhibition of tumor growth was even
      higher in animals treated with imatinib mesylate. CONCLUSIONS: Slug down
      regulation facilitates apoptosis induced by proapoptotic drugs in neuroblastoma
      cells and decreases their invasion capability in vitro and in vivo. Slug
      inhibition, possibly combined with imatinib mesylate, may represent a novel
      strategy for treatment of metastatic neuroblastoma.

PMID- 18628478
TI  - Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth
      factor-I receptor exhibits anticancer effect in esophageal adenocarcinoma in
      vitro and in vivo.
AB  - PURPOSE: Focal adhesion kinase (FAK) regulates integrin and growth factor
      mediated signaling pathways to enhance cell migration, proliferation, and
      survival, and its up-regulation correlates malignant grade and poor outcome in
      several types of cancer. In this study, we aimed to raise a potential therapeutic
      strategy using a FAK inhibitor for Barrett's esophageal adenocarcinoma.
      EXPERIMENTAL DESIGN: The expression status of FAK in clinical Barrett's
      esophageal adenocarcinoma tissues was determined by immunohistochemistry.
      Cultured esophageal adenocarcinoma cells were treated with TAE226, a specific FAK
      inhibitor with an additional effect of inhibiting insulin-like growth factor-I
      receptor (IGF-IR), to assess its anticancer effect in vitro. Western blot was
      carried out to explore a participating signaling pathway for TAE226-induced cell
      death. Furthermore, TAE226 was orally administered to s.c. xenograft animals to
      investigate its anticancer effect in vivo. RESULTS: Strong expression of FAK was
      found in 94.0% of Barrett's esophageal adenocarcinoma compared with 17.9% of
      Barrett's epithelia, suggesting that FAK might play a critical role in the
      progression of Barrett's esophageal adenocarcinoma. When esophageal
      adenocarcinoma cells were treated with TAE226, cell proliferation and migration
      were greatly inhibited with an apparent structural change of actin fiber and a
      loss of cell adhesion. The activities of FAK, IGF-IR, and AKT were suppressed by
      TAE226 and subsequent dephosphorylation of BAD at Ser(136) occurred, resulting in
      caspase-mediated apoptosis. In vivo tumor volume was significantly reduced by
      oral administration of TAE226. CONCLUSIONS: These results suggest that TAE226, a
      dual tyrosine kinase inhibitor for FAK and IGF-IR, could become a new remedy for
      Barrett's esophageal adenocarcinoma.

PMID- 18628479
TI  - Statin-dependent suppression of the Akt/mammalian target of rapamycin signaling
      cascade and programmed cell death 4 up-regulation in renal cell carcinoma.
AB  - PURPOSE: Statins are pharmacologic inhibitors of the 3-hydroxy-3-methylglutaryl
      coenzyme A reductase with potent regulatory effects on cholesterol biosynthesis
      in vitro and in vivo. There is accumulating evidence that, beyond their
      cholesterol-lowering properties, statins inhibit cell proliferation and promote
      apoptosis of malignant cells in vitro, but the mechanisms by which they generate
      such responses remain to be defined. EXPERIMENTAL DESIGN: Combinations of
      experimental approaches were used, including immunoblotting and cell
      proliferation and apoptosis assays. RESULTS: We provide evidence that fluvastatin
      is a potent inducer of apoptosis and suppresses proliferation of renal cell
      carcinoma (RCC) cells in vitro. Such effects are mediated by direct targeting of
      the Akt/mammalian target of rapamycin (mTOR) pathway, as evidenced by the
      suppression of phosphorylation/activation of Akt, resulting in inhibition of its
      downstream effectors, mTOR and p70 S6 kinase. In addition, fluvastatin blocks the
      mTOR-dependent phosphorylation/deactivation of the translational repressor
      eukaryotic initiation factor 4E (eIF4E)-binding protein, leading to the formation
      of eIF4E-binding protein-eIF4E complexes that suppress initiation of cap
      dependent mRNA translation. Importantly, inhibition of p70 S6 kinase activity by
      fluvastatin results in the up-regulation of expression of programmed cell death 4
      (PDCD4), a tumor suppressor protein with inhibitory effects on the translation
      initiation factor eIF4A, suggesting a mechanism for the generation of antitumor
      responses. CONCLUSIONS: Altogether, our findings establish that fluvastatin
      exhibits potent anti-RCC activities via inhibitory effects on the Akt/mTOR
      pathway and raise the possibility that combinations of statins and Akt inhibitors
      may be of future therapeutic value in the treatment of RCC.

PMID- 18628480
TI  - lenalidomide enhances natural killer cell and monocyte-mediated antibody
      dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells.
AB  - PURPOSE: Lenalidomide has significant activity in myelodysplastic syndromes,
      multiple myeloma, and non-Hodgkin's lymphoma (NHL). In previous studies, natural
      killer (NK) cell expansion by lenalidomide was shown to enhance the cytotoxic
      effect of rituximab. This study assessed the ability of lenalidomide to enhance
      antibody-dependent cellular cytotoxicity (ADCC) in rituximab-treated NHL cell
      lines and primary tumor cells from patients with B-cell chronic lymphocytic
      leukemia (B-CLL) in vitro. EXPERIMENTAL DESIGN: An in vitro ADCC system was used
      to assess the ability of lenalidomide to enhance human NK cell and monocyte
      function in response to rituximab. RESULTS: Lenalidomide directly enhanced IFN
      gamma production via Fc-gamma receptor-mediated signaling in response to IgG. It
      was also a potent enhancer of NK cell-mediated and monocyte-mediated tumor cell
      ADCC for a variety of rituximab-treated NHL cell lines in vitro, an effect that
      was dependent on the presence of antibody and either interleukin-2 or interleukin
      12. Lenalidomide also enhanced the ability of NK cells to kill primary tumor
      cells derived from three patients with B-CLL who have been treated previously
      with fludarabine plus cyclophosphamide. Enhanced NK cell ADCC was associated with
      enhanced granzyme B and Fas ligand expression and could be inhibited by a
      granzyme B inhibitor and partially inhibited by antibody to FasL. Enhanced NK
      cell Fc-gamma receptor signaling is associated with enhanced phosphorylated
      extracellular signal-related kinase levels leading to enhanced effector function.
      CONCLUSIONS: These findings suggest that lenalidomide has the potential to
      enhance the rituximab-induced killing of NHL cell lines and primary B-cell
      chronic lymphocytic leukemia cells via a NK cell-mediated and monocyte-mediated
      ADCC mechanism in vitro, providing a strong rationale for the combination of
      lenalidomide with IgG1 antibodies to target tumor-specific antigens in patients
      with cancer.

PMID- 18628481
TI  - Differential effect of doxorubicin and zoledronic acid on intraosseous versus
      extraosseous breast tumor growth in vivo.
AB  - PURPOSE: Breast cancer patients with bone metastases are commonly treated with
      chemotherapeutic agents such as doxorubicin and zoledronic acid to control their
      bone disease. Sequential administration of doxorubicin followed by zoledronic
      acid has been shown to increase tumor cell apoptosis in vitro. We have therefore
      investigated the antitumor effects of clinically relevant doses of these drugs in
      a mouse model of breast cancer bone metastasis. EXPERIMENTAL DESIGN: MDA-MB
      231/BO2 cells were injected via the tail vein into athymic mice. Tumor-induced
      osteolytic lesions were detected in all animals following X-ray analysis 18 days
      after tumor cell inoculation (day 18). Mice were administered saline, 100
      microg/kg zoledronic acid, 2 mg/kg doxorubicin, doxorubicin and zoledronic acid
      simultaneously, or doxorubicin followed 24 h later by zoledronic acid.
      Doxorubicin-treated animals received a second injection on day 25. Tumor growth
      in the marrow cavity and on the outside surface of the bone was measured as well
      as tumor cell apoptosis and proliferation. The effects of treatments on bone were
      evaluated following X-ray and muCT analysis. RESULTS: Sequential treatment with
      doxorubicin followed by zoledronic acid caused decreased intraosseous tumor
      burden, which was accompanied by increased levels of tumor cell apoptosis and
      decreased levels of proliferation, whereas extraosseous parts of the same tumors
      were unaffected. Administration of zoledronic acid, alone or in combination with
      doxorubicin, resulted in significantly smaller tumor-induced osteolytic lesions
      compared with control or doxorubicin-treated animals. CONCLUSIONS: This is the
      first study to show that sequential treatment with clinically relevant doses of
      doxorubicin, followed 24 h later by zoledronic acid, reduces intraosseous but not
      extraosseous growth of BO2 breast tumors. Our results suggest that breast cancer
      patients with metastatic bone disease may benefit from sequential treatment using
      doxorubicin and zoledronic acid.

PMID- 18628482
TI  - Penetrance analysis of the PALB2 c.1592delT founder mutation.
AB  - PURPOSE: PALB2 is a recently identified breast cancer susceptibility gene. We
      have previously identified in the Finnish population a PALB2 c.1592delT founder
      truncation mutation that is associated with an increased risk of breast cancer.
      In the present study, we wanted to assess in more detail the increased risk
      (hazard ratio, HR) and the age-specific cumulative risk (penetrance) of
      c.1592delT with regard to susceptibility to breast and other forms of cancer.
      EXPERIMENTAL DESIGN: Modified segregation analyses fitted under maximum
      likelihood theory were used to estimate age-specific cumulative risks and HRs
      using the families of mutation carriers identified from a consecutive series of
      breast cancer cases unselected for age at onset or family history. RESULTS: We
      found a substantially increased risk of breast cancer [HR, 6.1; 95% confidence
      interval (95% CI), 2.2-17.2; P = 0.01] equivalent to a 40% (95% CI, 17-77) breast
      cancer risk by age 70 years, comparable to that for carriers of mutations in
      BRCA2. We found marginal evidence (P = 0.06) that the HR for breast cancer
      decreased with age by 4.2% per year (95% CI, 0.2-8.1), from 7.5-fold at age 30
      years to 2.0-fold at age 60 years. CONCLUSIONS: Our results suggest that it may
      be appropriate to offer PALB2 c.1592delT mutation testing to Finnish women with
      breast cancer, especially those with an early age at onset or a family history of
      breast or related cancers, and to offer carriers the option of participation in
      extended disease surveillance programs.

PMID- 18628484
TI  - Calcium sensitization in human esophageal muscle: role for RhoA kinase in
      maintenance of lower esophageal sphincter tone.
AB  - A rise in intracellular-free calcium ([Ca(2+)](i)) concentration is important for
      initiating contraction of smooth muscles, and Ca(2+) sensitization involving RhoA
      kinase can sustain tension. We previously found that [Ca(2+)](i) was comparable
      in cells from the esophageal body (EB) and lower esophageal sphincter (LES)
      muscles, despite the fact that the LES maintains resting tone. We hypothesized
      that Ca(2+) sensitization contributes to contraction in human esophageal muscle.
      Tension and [Ca(2+)](i) were measured simultaneously in intact human EB and LES
      muscles using the ratiometric Ca(2+)-sensitive dye fura-2. Spontaneous
      oscillations in EB muscle tension were associated with transient elevations of
      [Ca(2+)](i). Carbachol caused a large increase in tension, compared with
      spontaneous oscillations, although the rise of [Ca(2+)](i) was similar,
      suggesting Ca(2+) sensitization. The RhoA-kinase blockers (R)-(+)-trans-4-(1
      aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y
      27632) and 1-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride (HA-1077)
      reduced carbachol- and nerve-evoked contraction of the EB, accompanied by smaller
      reduction in the rise of [Ca(2+)](i). Protein kinase C inhibitors reduced force
      to a lesser extent. RhoA-kinase blockers caused concentration-dependent reduction
      of tension in spontaneously contracted LES muscles. Moreover, RhoA-kinase
      blockers reduced intrinsic nerve-evoked and carbachol-evoked contraction.
      However, there was no effect on nerve- or nitric oxide-mediated relaxation of
      LES. Ca(2+) sensitization mediated by the RhoA-kinase pathway has an important
      role in contraction of human EB muscles and LES tonic contraction, a feature not
      previously recognized.

PMID- 18628483
TI  - A novel breast cancer-associated BRIP1 (FANCJ/BACH1) germ-line mutation impairs
      protein stability and function.
AB  - PURPOSE: BRCA1-interacting protein 1 (BRIP1; FANCJ/BACH1), which encodes a DNA
      helicase that interacts with BRCA1, has been suggested to be a low-penetrance
      breast cancer predisposing gene. We aimed to assess whether BRIP1 mutations
      contribute to breast cancer susceptibility in our population and, if so, to
      investigate the effect of such mutation(s) on BRIP1 function. EXPERIMENTAL
      DESIGN: A series of 49 breast/ovarian cancer families, devoid of a BRCA1/BRCA2
      mutation, were screened for BRIP1 mutations. Functional analyses, including
      coimmunoprecipitation and stability assays, were employed to further characterize
      a previously unreported variant. RESULTS: Five sequence alterations were
      identified, of which four had been already described. Herein, we report a novel
      BRIP1 germ-line mutation identified in a woman with early-onset breast cancer.
      The mutation consists of a 4-nucleotide deletion (c.2992-2995delAAGA) in BRIP1
      exon 20 that causes a shift in the reading frame, disrupts the BRCA1-binding
      domain of BRIP1, and creates a premature stop codon. Functional analysis of the
      recombinant mutant protein in transfected cells showed that the truncation
      interferes with the stability of the protein and with its ability to interact
      with BRCA1. Loss of the wild-type BRIP1 allele with retention of the mutated one
      was observed in the patient's breast tumor tissue. CONCLUSIONS: These results, by
      showing that the newly identified BRIP1 c.2992-2995delAAGA mutation is associated
      with instability and functional impairment of the encoded protein, provide
      further evidence of a breast cancer-related role for BRIP1.

PMID- 18628485
TI  - Effects of different levels of cigarette smoke exposure on prognostic heart rate
      and rate--pressure-product parameters.
AB  - Reduced cigarette smoke exposure in adult smokers switching from a conventional
      cigarette (CC) to a potential exposure-reduced electrically heated cigarette
      smoking system (EHCSS) and no smoking (NS) improved exercise performance. The
      effects of reduced smoke exposure on the prognostic parameters heart rate (HR)
      and rate-pressure-product (RPP) were investigated. A total of 18 male adult CC
      smokers were randomized in a 3-period cross-over study to CC, EHCSS, or to NS for
      3 days each before performing spiroergometry. Exposure parameters declined from
      CC to EHCSS and to NS. Resting HR and RPP increased from NS to EHCSS and to CC.
      Chronotropic response/HR recovery were more pronounced in NS than in EHCSS and
      CC. RPPmax was similar in NS and EHCSS and lowest during CC. Reduced tobacco
      smoke exposure for 3 days improved the prognostic parameters HR and RPP in an
      apparently dose-dependent manner.

PMID- 18628486
TI  - The epidemiology of United States high school soccer injuries, 2005-2007.
AB  - BACKGROUND: United States high school soccer participation increased 5 fold over
      the last 30 years. With increased participation comes increased injury incidence.
      HYPOTHESIS: High school soccer injury patterns will vary by gender and type of
      exposure. STUDY DESIGN: Descriptive epidemiologic study. METHODS: Soccer-related
      injury data were collected over the 2005-2006 and 2006-2007 school years from 100
      nationally representative United States high schools via Reporting Information
      Online (RIO, an Internet-based sports-related injury surveillance system).
      RESULTS: Participating certified athletic trainers reported 1524 soccer injuries
      during 637 446 athlete exposures (AEs), for an injury rate of 2.39 per 1000 AEs,
      corresponding to a nationally estimated 807 492 soccer-related injuries during
      the 2005-2006 and 2006-2007 seasons. The injury rate per 1000 AEs was greater
      during competition (4.77) than practice (1.37) (rate ratio [RR] = 3.49; 95%
      confidence interval [CI], 3.15-3.87). Overall, the most frequent diagnoses were
      incomplete ligament sprains (26.8%), incomplete muscle strains (17.9%),
      contusions (13.8%), and concussions (10.8%). The most commonly injured body sites
      were the ankle (23.4%), knee (18.7%), head/face (13.7%), and thigh/upper leg
      (13.1%). Similar proportions of boys (57.9%) and girls (53.9%) returned to
      activity in <1 week. During competition, girls sustained complete knee ligament
      sprains requiring surgery at a rate of 26.4 per 100 000 AEs, higher than the rate
      among boys during competition (1.98 per 100 000 AEs) (RR = 13.3; 95% CI, 3.15
      56.35) and among girls during practice (2.34 per 100 000 AEs) (RR = 11.3; 95% CI,
      4.31-29.58). Player-to-player contact was more common among competition injuries
      (injury proportion ratio [IPR] = 2.42; 95% CI, 2.01-2.92), while noncontact
      mechanisms were more common among practice injuries (IPR = 2.39; 95% CI, 1.90
      3.01). CONCLUSIONS: High school soccer injury patterns vary by gender and type of
      exposure. Identifying such differences in injury patterns is the important first
      step in the development of evidence-based, targeted injury prevention efforts.

PMID- 18628487
TI  - The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a
      high-risk group of patients with shortened time to disease progression and poorer
      overall survival.
AB  - The International Prognostic Index and the Follicular Lymphoma International
      Prognostic Index are widely used for the risk assessment of follicular lymphoma
      (FL). Although molecular studies have provided insight into the biology of FL, no
      molecular marker has impacted on treatment stratification. Because TP53 mutations
      are associated with poor prognosis in hematologic malignancies, we investigated
      the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53
      mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated
      with older age (P = .02) and higher International Prognostic Index score (P =
      .04). On multivariate analysis, TP53 mutation correlated with shorter progression
      free survival (P < .001) and overall survival (P = .009). TP53 mutation was
      associated with low expression of the immune-response 1 gene expression signature
      (P = .016) and with an unfavorable gene expression-based survival predictor score
      (P < .001), demonstrating for the first time that molecular features of the
      malignant cell may correlate with the nature of the immune response in FL.

PMID- 18628489
TI  - Overexpression of B cell-activating factor of TNF family (BAFF) is associated
      with Helicobacter pylori-independent growth of gastric diffuse large B-cell
      lymphoma with histologic evidence of MALT lymphoma.
AB  - We have recently demonstrated that nuclear expression of BCL10 predicts
      Helicobacter pylori (HP) independence of early-stage gastric diffuse large B-cell
      lymphoma (DLBCL) with histologic evidence of mucosa-associated lymphoid tissue
      (MALT). In this study, we examined the role of B cell-activating factor of TNF
      family (BAFF) in mediating BCL10 nuclear translocation and HP independence of
      gastric DLBCL (MALT). We used immunohistochemistry and immunoblotting to measure
      the expression of BAFF, pAKT, BCL3, BCL10, and NF-kappaB. Transactivity of NF
      kappaB was measured by electromobility shift assay. In lymphoma samples from 26
      patients with gastric DLBCL (MALT), we detected aberrant expression of BAFF in 7
      of 10 (70%) HP-independent and in 3 of 16 (18.8%) HP-dependent cases (P = .015).
      BAFF overexpression was associated with pAKT expression (P = .032), and nuclear
      expression of BCL3 (P = .014), BCL10 (P = .015), and NF-kappaB (P = .004). In B
      cell lymphoma Pfeiffer cells, BAFF activated NF-kappaB and AKT; the activated NF
      kappaB up-regulated BCL10, and the activated AKT caused formation of BCL10/BCL3
      complexes that translocated to the nucleus. Inhibition of AKT by LY294002 (a PI3K
      inhibitor) blocked BCL10 nuclear translocation, NF-kappaB transactivity, and BAFF
      expression. Our results indicate that autocrine BAFF signal transduction pathways
      may contribute to HP-independent growth of gastric DLBCL (MALT).

PMID- 18628490
TI  - Francisella tularensis: unravelling the secrets of an intracellular pathogen.
AB  - Francisella tularensis has been recognized as the causative agent of tularaemia
      for almost a century. Since its discovery in 1911, it has been shown to infect a
      wide range of hosts, including humans. As early as the 1920s it was suggested to
      be an intracellular pathogen, but it has proven to be an enigmatic organism,
      whose interaction with the host has been difficult to elucidate, and we still
      have a very limited understanding of the molecular mechanisms of virulence.
      However, the recent availability of genome sequence data and molecular tools has
      allowed us to start to understand the molecular basis of F. tularensis
      pathogenicity, and will facilitate the development of a vaccine to protect
      against infection.

PMID- 18628488
TI  - Tissue-type plasminogen activator and the low-density lipoprotein receptor
      related protein induce Akt phosphorylation in the ischemic brain.
AB  - Tissue-type plasminogen activator (tPA) is found in the intravascular space and
      in the central nervous system. The low-density lipoprotein receptor-related
      protein (LRP) is expressed in neurons and in perivascular astrocytes. During
      cerebral ischemia, tPA induces the shedding of LRP's extracellular domain from
      perivascular astrocytes, and this is followed by the development of cerebral
      edema. Protein kinase B (Akt) is a serine/threonine kinase that plays a critical
      role not only in cell survival but also in the regulation of the permeability of
      the blood-brain barrier. We found that, in the early phases of the ischemic
      insult, the interaction between tPA and LRP induces Akt phosphorylation (pAkt) in
      perivascular astrocytes and inhibits pAkt in neurons. Coimmunoprecipitation
      studies indicate that pAkt and LRP's intracellular domain interact in
      perivascular astrocytes and that this interaction is dependent on the presence of
      tPA and results in the development of edema. Together, these results indicate
      that, in the early stages of cerebral ischemia, the interaction between tPA and
      LRP in perivascular astrocytes induces the activation of a cell signaling event
      mediated by pAkt that leads to increase in the permeability of the blood-brain
      barrier.

PMID- 18628491
TI  - The Lon protease regulates swarming motility and virulence gene expression in
      Proteus mirabilis.
AB  - A mini-Tn5lacZ1 transposon insertion in a gene encoding an orthologue of the Lon
      protease conferred a hyper-swarming phenotype on Proteus mirabilis. The lon
      mutation increased the accumulation of mRNA for representative class 1 (flhDC),
      class 2 (fliA) and class 3 (flaA) genes during swarmer cell differentiation. In
      addition, the stability of the FlhD protein was fourfold higher in the lon : mini
      Tn5lacZ1 background. Expression of a single-copy lon : lacZ fusion increased
      during the swarming cycle and reached peak levels of expression at a point just
      after swarmer cell differentiation had initiated. In liquid media, a condition
      normally non-permissive for swarming, the lon : : mini-Tn5lacZ1 insertion
      resulted in motile, highly elongated cells that overexpressed flagellin. Finally,
      the lon : : mini-Tn5lacZ1 mutation was shown to result in increased expression of
      the hpmBA and zapA virulence genes during swarmer cell differentiation.

PMID- 18628492
TI  - Growth-phase regulation of lipopolysaccharide O-antigen chain length influences
      serum resistance in serovars of Salmonella.
AB  - The amount of lipopolysaccharide (LPS) O antigen (OAg) and its chain length
      distribution are important factors that protect bacteria from serum complement.
      Salmonella enterica serovar Typhi produces LPS with long chain length
      distribution (L-OAg) controlled by the wzz gene, whereas serovar Typhimurium
      produces LPS with two OAg chain lengths: an L-OAg controlled by Wzz(ST) and a
      very long (VL) OAg determined by Wzz(fepE). This study shows that serovar
      Enteritidis also has a bimodal OAg distribution with two preferred OAg chain
      lengths similar to serovar Typhimurium. It was reported previously that OAg
      production by S. Typhi increases at the late exponential and stationary phases of
      growth. The results of this study demonstrate that increased amounts of L-OAg
      produced by S. Typhi grown to stationary phase confer higher levels of bacterial
      resistance to human serum. Production of OAg by serovars Typhimurium and
      Enteritidis was also under growth-phase-dependent regulation; however, while the
      total amount of OAg increased during growth, the VL-OAg distribution remained
      constant. The VL-OAg distribution was primarily responsible for complement
      resistance, protecting the non-typhoidal serovars from the lytic action of serum
      irrespective of the growth phase. As a result, the non-typhoidal species were
      significantly more resistant than S. Typhi to human serum. When S. Typhi was
      transformed with a multicopy plasmid containing the S. Typhimurium wzz(fepE)
      gene, resistance to serum increased to levels comparable to the non-typhoidal
      serovars. In contrast to the relevant role for high-molecular-mass OAg molecules,
      the presence of Vi antigen did not contribute to serum resistance of clinical
      isolates of serovar Typhi.

PMID- 18628493
TI  - Double-antigen sandwich time-resolved immunofluorometric assay for the detection
      of anti-hepatitis C virus total antibodies with improved specificity and
      sensitivity.
AB  - Current anti-hepatitis C virus (HCV) antibody screening immunoassays are
      routinely based on an indirect format. Although their use for anti-HCV antibody
      detection has achieved a very high specificity and sensitivity, false-positive
      results are still a problem especially among populations with a low prevalence of
      HCV infection. One strategy to obviate this problem is to adapt the assay from an
      indirect format to a double-antigen sandwich one to further improve its
      specificity. In this study, a double-antigen sandwich time-resolved
      immunofluorometric assay (DAS-TRIFMA) has been developed to detect total anti-HCV
      antibodies based on biotin-streptavidin interaction. For comparison, 1025 samples
      were analysed by the DAS-TRIFMA and three indirect anti-HCV antibody detection
      methods. For samples with discordant results, PCR-ELISA and Inno-LIA were
      employed as supplementary assays to analyse the presence of HCV antibodies. With
      regard to the 1025 clinical samples, the overall concordance between the DAS
      TRIFMA and the three indirect methods was 99.41, 98.93 and 98.93 % for Ortho
      ELISA 3.0, WAT ELISA and I-TRIFMA, respectively. The specificity/sensitivity of
      the DAS-TRIFMA, Ortho HCV ELISA 3.0, WAT HCV ELISA and I-TRIFMA were 100/99.09,
      99.34/98.18, 99.23/97.27 and 99.01 %/98.18 %, respectively. The DAS-TRIFMA was
      able to detect HCV antibodies at a concentration about 1/10 of that detectable by
      indirect methods. From the obtained results and their comparison, it is concluded
      that the DAS-TRIFMA is a more specific and reliable method for screening anti-HCV
      antibodies, and weakly positive S/Co values by the DAS-TRIFMA were more
      predictive of HCV infection than those by indirect methods.

PMID- 18628494
TI  - Agar dilution and agar screen with cefoxitin and oxacillin: what is known and
      what is unknown in detection of meticillin-resistant Staphylococcus aureus.
AB  - In this study we evaluated the performance of the oxacillin agar screen test, and
      agar dilution tests using cefoxitin and oxacillin antimicrobials, to detect
      meticillin resistance in Staphylococcus aureus isolates. The presence of the mecA
      gene, detected by PCR, was used as the standard to which agar screen and agar
      dilution tests were compared. The best performance was obtained using the agar
      dilution test (99.4 % accuracy) with breakpoints of 4 mug ml(-1) for oxacillin
      and 8 mug ml(-1) for cefoxitin, and using the oxacillin agar screen test. Also, a
      strong correlation between MIC values of cefoxitin and oxacillin permits the use
      of either drug for detection of meticillin resistance.

PMID- 18628495
TI  - Cefoxitin disc diffusion test for detection of meticillin-resistant
      staphylococci.
AB  - Staphylococci are the main causative agents of nosocomial diseases. Over the last
      few years, the increase in the number of meticillin-resistant (MR) staphylococci
      has become a major clinical problem. Accuracy and promptness in the detection of
      meticillin resistance are of key importance in ensuring the correct antibiotic
      treatment in infected patients and control of MR staphylococci in the hospital
      environment. This study evaluated the accuracy of a cefoxitin disc diffusion (DD)
      test for the detection of meticillin resistance in staphylococci. A total of 144
      clinical isolates [97 Staphylococcus aureus and 47 coagulase-negative
      staphylococci (CoNS)] were tested using a mecA gene PCR, a DD test (oxacillin, 1
      mug disc; cefoxitin, 30 mug disc), determination of oxacillin MIC by agar
      dilution (AD), and an oxacillin screen agar test at oxacillin concentrations of 4
      and 6 mug ml(-1). Of the 97 S. aureus and 47 CoNS isolates, 73 (75.26 %) and 30
      (63.83 %), respectively, were mecA-positive. The sensitivity and specificity of
      the cefoxitin DD test were 94.44 and 95.83 %, respectively, for S. aureus and 80
      and 100 %, respectively, for CoNS. The oxacillin DD method was 100 % sensitive
      and 58.33 % specific for S. aureus, and 86.67 % sensitive and 70.59 % specific
      for CoNS. The AD test was highly sensitive (98.63 %) and specific (98.53 %) for
      S. aureus and CoNS (83.33 % sensitive and 94.12 % specific). The cefoxitin DD
      test for meticillin-resistance detection was more specific but less sensitive
      than the oxacillin DD test. Use of DD tests for both cefoxitin and oxacillin can
      help in more accurate prediction of meticillin resistance. Centres that are not
      equipped to carry out PCR can use AD methods for confirmation of meticillin
      resistance, especially in oxacillin-resistant and cefoxitin-sensitive cases.

PMID- 18628496
TI  - A comparison of two methods for the diagnosis of lymphogranuloma venereum.
AB  - A recent outbreak of lymphogranuloma venereum (LGV) within the men who have sex
      with men (MSM) community and their requirement for extended therapy has
      highlighted the need for laboratory tests that differentiate LGV- from non-LGV
      associated serovars of Chlamydia trachomatis. Two previously described methods
      were evaluated against 495 clinical specimens referred to the Sexually
      Transmitted Bacteria Reference Laboratory (London, UK): (i) PCR amplification of
      a 1.1 kb region of the ompI gene followed by restriction enzyme digestion (ompI
      RFLP-PCR); and (ii) real-time PCR targeting a 36 bp deletion present within the
      polymorphic membrane protein H gene of LGV-associated serovars (pmpH real-time
      PCR). For specimens that could be categorized using both methods, a 94.7 %
      (390/412) concordance was achieved. Eighty-three specimens were found to be
      untypeable by ompI RFLP-PCR due to a failure to amplify the 1.1 kb fragment. Of
      these 83 untypeable specimens, 19 were determined to be an LGV-associated serovar
      by pmpH real-time PCR. Despite the high level of concordance, there were
      differences found in the technical complexity of the two methods. The pmpH real
      time PCR exhibited greater sensitivity, a more rapid turnaround time and a lower
      technical requirement. Whilst the ompI RFLP-PCR was not as robust as a laboratory
      diagnostic method, it did enable serovar-level identification. LGV infection
      remains an important threat to the health of high-risk MSM in Europe. In
      conclusion, the two methods for the detection of LGV from clinical samples were
      found not only to have a high concordance (94.7 %) but also to be complementary,
      and could be used in an integrated way to aid LGV detection.

PMID- 18628497
TI  - Efficacy of common hospital biocides with biofilms of multi-drug resistant
      clinical isolates.
AB  - The hospital environment is particularly susceptible to contamination by
      bacterial pathogens that grow on surfaces in biofilms. The effects of hospital
      biocides on two nosocomial pathogens, meticillin-resistant Staphylococcus aureus
      (MRSA) and Pseudomonas aeruginosa, growing as free-floating (planktonic) and
      adherent biofilm populations (sessile) were examined. Clinical isolates of MRSA
      and P. aeruginosa were grown as biofilms on discs of materials found in the
      hospital environment (stainless steel, glass, polyethylene and Teflon) and
      treated with three commonly used hospital biocides containing benzalkonium
      chloride (1 % w/v), chlorhexidine gluconate (4 % w/v) and triclosan (1 % w/v).
      Cell viability following biocide treatment was determined using an XTT assay and
      the LIVE/DEAD BacLight Bacterial Viability kit. The minimum bactericidal
      concentration (MBC) of all biocides for planktonic populations of both organisms
      was considerably less than the concentration recommended for use by the
      manufacturer. However, when isolates were grown as biofilms, the biocides were
      ineffective at killing bacteria at the concentrations recommended for use.
      Following biocide treatment, 0-11 % of cells in MRSA biofilms survived, and up to
      80 % of cells in P. aeruginosa biofilms survived. This study suggests that
      although biocides may be effective against planktonic populations of bacteria,
      some biocides currently used in hospitals are ineffective against nosocomial
      pathogens growing as biofilms attached to surfaces and fail to control this
      reservoir for hospital-acquired infection.

PMID- 18628498
TI  - Potency of IMP-10 metallo-beta-lactamase in hydrolysing various antipseudomonal
      beta-lactams.
AB  - Limited beta-lactams show antipseudomonal activity. The rapid spread of IMP-type
      metallo-beta-lactamases (MBLs), which have a broad spectrum of substrates and a
      poor susceptibility to clinically available inhibitors, further restricts beta
      lactam use. In the present study, we evaluated the potency of IMP-10 MBL in
      hydrolysing antipseudomonal beta-lactams currently available in the clinic. Crude
      IMP-10 MBL was prepared from two clinical isolates of Pseudomonas aeruginosa
      harbouring the bla(IMP-10) gene. The sensitivity of beta-lactams to hydrolysis by
      IMP-10 MBL was determined by comparing the MICs of 14 antipseudomonal beta
      lactams against a susceptible strain of P. aeruginosa in the presence and absence
      of IMP-10 MBL. Carbapenems (imipenem, meropenem and panipenem) and extended
      spectrum cephems (ceftazidime, cefoperazone, cefsulodin and cefepime) were
      sensitive to the hydrolysing activity of IMP-10 MBL. By comparison, the fourth
      generation cephem (cefpirome), the extended-spectrum penicillins (carbenicillin,
      ticarcillin, piperacillin and mezlocillin) and monobactams (aztreonam and
      carumonam) were relatively resistant to IMP-10 MBL. The sensitivity profile of
      antipseudomonal beta-lactams to IMP-10 MBL generated in the present study
      provides a valuable reference for antibiotic selection by medical professionals.

PMID- 18628499
TI  - Presence of pathogenic Borrelia burgdorferi sensu lato in ticks and rodents in
      Zhejiang, south-east China.
AB  - A molecular epidemiological survey was conducted to investigate the presence of
      pathogenic Borrelia burgdorferi sensu lato (s.l.) species in the forest areas of
      Zhejiang province, south-east China. A total of 182 ticks of 6 species and 200
      rodents of 8 species were collected and individually examined for the presence of
      B. burgdorferi s.l. DNA by nested PCR targeting the 5S-23S rRNA intergenic
      spacer. Forty-one ticks of four species, Haemaphysalis concinna, Haemaphysalis
      longicornis, Rhipicephalus microplus and Haemaphysalis warburconi, were infected
      with B. burgdorferi s.l., with an overall infection rate of 23 %. Sixteen rodents
      of four species, Nivivener confucianus, Nivivener coxingi, Apodemus sylvaticus
      and Rattus losea, were positive for B. burgdorferi s.l., with an overall
      prevalence of 8 %. MseI RFLP analysis and sequence analysis of the positive PCR
      products showed that Borrelia spirochaetes in specimens consisted of Borrelia
      garinii, Borrelia afzelii and Borrelia valaisiana-related group. Forty (98 %) of
      the B. burgdorferi s.l.-positive ticks were infected with B. garinii and one (2
      %) was infected with B. afzelii. Twelve (75 %) of the positive rodents were
      infected with B. garinii and four (25 %) were infected with the Borrelia
      spirochaete belonging to B. valaisiana-related group.

PMID- 18628500
TI  - Prevalence of Anaplasma phagocytophilum and its coinfection with Borrelia afzelii
      in Ixodes ricinus and Ixodes persulcatus ticks inhabiting Tver Province (Russia) 
      a sympatric region for both tick species.
AB  - Human granulocytic anaplasmosis (HGA) and Lyme borreliosis (LB) are tick-borne
      infectious diseases caused by Anaplasma phagocytophilum and Borrelia burgdorferi
      sensu lato species, respectively. In this study, p44/msp2 paralogues specific to
      A. phagocytophilum and 5S-23S rRNA gene-intergenic spacers specific to B.
      burgdorferi sensu lato species were detected by PCR in ticks collected in two
      regions, Tver (Kalinin) and Konakovo, of the Tver (Kalinin) Province located 150
      km north-west of Moscow. The PCR amplicons obtained were further characterized by
      sequencing and RFLP analysis. In the total of 199 ticks collected, 8.8 % (7/80)
      and 33.8 % (27/80) of Ixodes ricinus, and 2.5 % (3/119) and 45.4 % (54/119) of
      Ixodes persulcatus, were found to be infected with A. phagocytophilum and B.
      burgdorferi sensu lato spp., respectively. Of those 199 ticks, 5 (2.5 %) were
      coinfected with A. phagocytophilum and Borrelia afzelii. Phylogenetic analysis
      revealed unique p44/msp2 paralogous genes in A. phagocytophilum-infected Russian
      ticks. The sequence similarities with those of A. phagocytophilum in the United
      States, UK and Japan ranged from 42 % to 80.4 %, and there were no sequences
      showing more than 90 % similarity with those sequences from the other countries.
      The results showed that the p44/msp2 sequence similarity groups may provide an
      index of adaptation of A. phagocytophilum strains to specific vector ticks or
      reservoir hosts in different countries and areas. These findings suggest that
      there is a public health threat from HGA and LB in Tver Province surrounding
      Moscow.

PMID- 18628501
TI  - A new serotype 14 variant of the pneumococcal Spain9V-3 international clone
      detected in the central region of Argentina.
AB  - The penicillin-resistant Spain(9V)-3 clone of Streptococcus pneumoniae is
      widespread and presents different serotype variants originating from
      recombination of the capsular genes. In this work, the genetic relatedness of 29
      invasive pneumococci isolated from the central region of Argentina (Cordoba,
      Buenos Aires, Santa Fe and La Pampa provinces) was assessed by multilocus
      sequence typing (MLST). All of the penicillin-non-susceptible isolates studied
      (21/29) belonged to a serotype 14 variant of the Spain(9V)-3 clone. This clone
      was predominant, suggesting that it was responsible for the penicillin resistance
      spread in this region. Interestingly, this serotype 14 variant (named Cordoba
      S14V) could be differentiated from the European one by its pbp1a gene, suggesting
      a different recombinational replacement of the capsular genes. The putative
      recombination sites were analysed, resulting in the proximal crossover point
      being clearly localized in the spr0309 gene, with the distal site restricted to
      the recU gene, confirming a different recombination event. Analysis of the dexB,
      cpsB, aliA and pbp1a genes from these strains showed a high similarity with the
      corresponding genes of the Spain(14)-5 clone, suggesting that the capsular genes
      were provided by this international clone. Analysis of the genetic polymorphisms
      of the pbp1a (nt 1473-1922) and spr0309 (nt 1-790) genes is proposed as an
      epidemiological tool to help recognize the Cordoba S14V of the Spain(9V)-3 clone.
      On the other hand, BOX-repeat-based PCR and MLST analyses of serotype 14 strains
      revealed a divergent epidemiology of the Cordoba S14V, suggesting a non-recent
      dissemination in the paediatric population. It is suggested that this molecular
      epidemiology work will be a reference for monitoring the evolution of S14Vs of
      Spain(9V)-3, the emergence of new clones and the impact of pneumococcal
      vaccination programmes in Argentina.

PMID- 18628502
TI  - A convenient rapid culture assay for the detection of enteroviruses in clinical
      samples: comparison with conventional cell culture and RT-PCR.
AB  - A convenient rapid culture assay (RCA) for the detection of enteroviruses was
      evaluated against RT-PCR using 576 stool and 102 cerebrospinal fluid (CSF)
      samples. One hundred and ninety stool samples were also tested by conventional
      cell culture (CCC). The RCA used immunoperoxidase staining of cell culture plates
      with a blend of monoclonal antibodies (mAbs) against enterovirus VP1 on the
      second and sixth days after inoculation. This blend was composed of 5D8/1 (Dako)
      and four 'in-house' mAbs. CCC was performed using fluorescence staining with the
      Enterovirus Screening Set (Chemicon International) for culture confirmation.
      Detection of enteroviruses by the RCA was more successful in colonic carcinoma
      (CaCo-2) and rhabdomyosarcoma (RD) cells than in human embryonic lung
      fibroblasts, HEp2 and A549 cells. The performance of CCC in RD cells was hindered
      by rapid cell degeneration and non-specific staining of cells during culture
      confirmation. The sensitivity of the RCA compared to RT-PCR in stool samples was
      found to be 71 % (115/161) on the second day and 87 % (140/161) on the sixth day.
      The sensitivity of the RCA in CSF samples was 38 % (22/58) after 2 days and 59 %
      (34/58) after 6 days. The specificity of the RCA was 100 %. All CCC-positive
      samples were positive by the RCA. CCC required 3-14 days for virus recovery. In
      conclusion, the RCA has the same sensitivity as CCC, significantly shortens the
      time required for the detection of enteroviruses, and prevents pitfalls
      associated with using RD cells for CCC. For diagnosis of aseptic meningitis in
      CSF samples, RT-PCR should be performed.

PMID- 18628503
TI  - Impact of antibiotics on the gut microbiota of critically ill patients.
AB  - We evaluated the relationship between the intestinal microbiota composition and
      clinical outcome in a group of 15 high-risk patients admitted for acute infection
      and/or surgical/accidental trauma who were treated with systemic antibiotics
      according to standard intensive care unit (ICU) protocols. There was a high
      mortality rate amongst these patients, each of whom had a considerable organ
      failure score at admission, respiratory assistance during the most of their ICU
      stay and a long length of stay. All of these individuals received sedation and
      enteral nutrition, and the majority also received insulin, vasoactive drugs and
      some stress-ulcer prophylaxis agents. The intestinal microbiota composition was
      assessed using denaturing gradient gel electrophoresis (DGGE), a molecular
      biology tool used to characterize bacterial ecosystems. As all of the patient
      subjects were in good health prior to their acute illness and admission to the
      ICU, the first faecal samples obtained from this group showed a DGGE banding
      pattern that was similar to that of healthy subjects. After 1 week of critical
      illness, coupled with intensive care treatment, including antibiotics, a very
      definite alteration in the overall microbiota composition was evident, as
      revealed by a reduction in the number of DGGE bands. Further pronounced changes
      to the DGGE banding profiles could be observed in patients remaining in the ICU
      for 2 weeks. Moreover, a dominant band, identified by sequencing as highly
      related to Enterococcus, was detected in the DGGE profile of some of our patient
      subjects. We also performed real-time PCR and obtained results that were in
      agreement with our qualitative evaluations using DGGE. The degree of organ
      failure and ICU mortality was significantly higher in patients for whom a high
      reduction in microbiota biodiversity was coupled with a massive presence of
      enterococci. A statistically significant link between these two ecological traits
      and the use of clindamycin was also found.

PMID- 18628504
TI  - Increase in the frequency of recovery of meticillin-resistant Staphylococcus
      aureus in acute and chronic maxillary sinusitis.
AB  - This study compared the rate of recovery of meticillin-resistant Staphylococcus
      aureus (MRSA) between the periods 2001-2003 and 2004-2006 in acute and chronic
      maxillary sinusitis. Cultures were obtained from 458 patients, 244 with acute and
      214 with chronic maxillary sinusitis; 215 isolates were recovered in the 2 years
      between 2001 and 2003 (118 from acute and 97 from chronic sinusitis), and 243 in
      the 2 years between 2004 and 2006 (126 from acute and 117 from chronic
      sinusitis). S. aureus was isolated from ten (8 %) of the patients with acute
      sinusitis between 2001 and 2003, three (30 %) of which were MRSA, and from 13 (10
      %) of the patients with acute sinusitis between 2004 and 2006, nine (69 %) of
      which were MRSA (P <0.01). S. aureus was found in 15 (15 %) of the patients with
      chronic sinusitis between 2001 and 2003, four (27 %) of which were MRSA, and from
      23 (20 %) of the patients with chronic sinusitis between 2004 and 2006, 14 (61 %)
      of which were MRSA (P <0.05). Antimicrobial therapy was administered over the
      last 3 months to 122 (57 %) of the patients with chronic sinusitis. MRSA was
      isolated more often from these individuals (28/122; 23 %) than from those not
      treated previously (10/92 or 11 %) (P <0.05). These data illustrate that a
      significant increase occurred in the rate of recovery of MRSA in patients with
      acute and chronic maxillary sinusitis over the periods studied.

PMID- 18628505
TI  - Biofilm formation by Scottish clinical isolates of Staphylococcus aureus.
AB  - The biofilm-forming capacity of 972 clinical isolates of Staphylococcus aureus
      was tested using a high-throughput polystyrene 96-peg plate format. Isolates of
      S. aureus were collected from patients in hospitals throughout Scotland from 2004
      to 2006; 763 of these were meticillin-resistant S. aureus (MRSA) and 209 were
      meticillin-sensitive S. aureus (MSSA). The biomass of each biofilm was quantified
      using a crystal violet staining technique. Isolates were divided into those that
      formed fully established biofilms, moderately attached biofilms and weakly
      adherent biofilms by comparison with a known biofilm-forming strain. The majority
      of MRSA (53.8 %) and MSSA (43.5 %) isolates formed moderately attached biofilms.
      Fully established biofilms were formed by 20.5 % of MRSA isolates and 28.0 % of
      MSSA isolates, whilst 25.7 % of MRSA isolates and 28.5 % of MSSA isolates formed
      negligible biofilms. There was no significant correlation between susceptibility
      to meticillin and biofilm formation (P=0.77). MRSA isolates were divided into
      clonal types (EMRSA-15, EMRSA-16 and sporadic isolates) based on PFGE genotyping
      results. EMRSA-15 isolates formed significantly more moderately and fully
      established biofilms than EMRSA-16 isolates (P<0.001). S. aureus strains isolated
      from the skin of patients had a significantly greater capacity to form biofilms
      than isolates from other body sites, including the blood. Microscopic examination
      of biofilms by scanning electron microscopy (SEM) revealed that poorly adherent
      biofilm formers failed to colonize the entire surface of the peg, whilst
      moderately adherent biofilm formers grew in uniform monolayers but failed to
      develop a mature three-dimensional structure. SEM analysis of an isolate
      representative of the group that formed fully established biofilms confirmed that
      this isolate developed a dense biofilm with a textured, multi-layered, three
      dimensional structure.

PMID- 18628506
TI  - Rapid detection of multidrug-resistant Mycobacterium tuberculosis in Cotonou
      (Benin) using two low-cost colorimetric methods: resazurin and nitrate reductase
      assays.
AB  - We have evaluated two simple, rapid and low-cost colorimetric methods for the
      detection of multidrug-resistant Mycobacterium tuberculosis. A total of 151 M.
      tuberculosis strains were tested for resistance to rifampicin (RMP) and isoniazid
      by resazurin microplate assay (REMA) and nitrate reductase assay (NRA) in
      comparison with the conventional proportion method (PM) on Lowenstein-Jensen
      medium. A complete agreement was found between NRA and PM, while one false RMP
      susceptible result was found by REMA. REMA and NRA tests are rapid and
      inexpensive, and could be good alternatives to the conventional PM in low
      resource countries.

PMID- 18628507
TI  - Angio-oedema as an unusual tolerable side effect of voriconazole therapy.
AB  - Voriconazole (VRC) has not previously been reported to cause angio-oedema. Here,
      we report a case of angio-oedema associated with VRC therapy. A 37-year-old woman
      with relapsing invasive vertebral aspergillosis received intravenous VRC and
      developed angio-oedema 10 days after starting therapy. This condition rapidly
      diminished after administration of intravenous antihistaminics and did not
      necessitate cessation of VRC treatment. The treatment was continued for 6 months
      without recurrence of the symptoms. After 18 months, the patient was in good
      health. To our knowledge, this is the first report of an angio-oedema associated
      with VRC.

PMID- 18628508
TI  - Lamivudine-induced red cell aplasia.
AB  - Anaemia is frequent in patients with human immunodeficiency virus infection, and
      antiretroviral drugs have been implicated. Whilst therapy-induced anaemia is more
      readily attributed to zidovudine, lamivudine-associated, potentially life
      threatening, pure red cell aplasia (PRCA) has been less recognized in the past
      and is only infrequently documented in the literature. We report on a patient
      suffering from what turned out to be lamivudine-induced PRCA who required 15
      units of blood within 3 weeks before recovering swiftly following lamivudine
      (3TC) treatment withdrawal. As reviewed here, the nature of this condition is not
      well described in general, the onset appears to be variable and occurs at any
      CD4(+) count, but rapid improvement after cessation of drug administration
      appears to be a consistent feature.

PMID- 18628509
TI  - Daptomycin non-susceptible meticillin-resistant Staphylococcus aureus USA 300
      isolate.
AB  - Daptomycin is a novel bactericidal agent active against Gram-positive pathogens
      including meticillin-resistant Staphylococcus aureus (MRSA). Our case is unique
      in the description of an MRSA USA 300 isolate that developed decreased
      susceptibility to daptomycin during daptomycin and vancomycin therapy. Directed
      sequencing detected a previously reported mutation in mprF, resulting in a T345A
      substitution, associated with non-susceptibility to daptomycin.

PMID- 18628510
TI  - An overview of the phenotypic and genotypic characteristics of multidrug
      resistant Mycobacterium tuberculosis isolates from four Asian countries.

PMID- 18628511
TI  - Functional independence of a variant LuxOPL91 from a non-O1 non-O139 Vibrio
      cholerae over the activity of CsrA and Fis.

PMID- 18628512
TI  - Is nalidixic acid resistance linked to clinical virulence in Salmonella enterica
      serovar Typhi infections?

PMID- 18628513
TI  - Low sensitivity of Bartonella henselae PCR in serum samples of patients with cat
      scratch disease lymphadenitis.

PMID- 18628514
TI  - Large genomic deletions in AIP in pituitary adenoma predisposition.
AB  - CONTEXT: Germline mutations in AIP have been recently shown to cause pituitary
      adenoma predisposition (PAP). Subsequently, many intragenic germline mutations
      have been reported, both in familial and in sporadic settings. OBJECTIVE: Our
      objective was to evaluate the possible contribution of large genomic germline AIP
      deletions, an important mutation type in tumor predisposition syndromes, in PAP.
      DESIGN: Here, we applied the multiplex ligation-dependent probe amplification
      assay to examine whether large genomic AIP or MEN1 alterations account for a
      subset of PAP cases. PATIENTS: The study was performed on familial and sporadic
      pituitary adenoma cases of European origin, which had previously tested negative
      for germline AIP and MEN1 mutations by sequencing. RESULTS: Two of 21 pituitary
      adenoma families (9.5%) were found to harbor an AIP deletion. No copy number
      changes were detected among 67 sporadic pituitary adenoma patients. No MEN1
      deletions were found. CONCLUSIONS: The present study shows that large genomic AIP
      deletions account for a subset of PAP. Therefore, in suspected PAP cases
      undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe
      amplification could be considered if direct sequencing does not identify a
      mutation.

PMID- 18628515
TI  - Predictors of autoimmune hyperthyroidism relapse in children after
      discontinuation of antithyroid drug treatment.
AB  - CONTEXT: There is debate about how Graves' disease (GD) should be treated in
      children. OBJECTIVE: The aim of this study was to identify predictors of relapse
      after antithyroid drug (ATD) treatment in children with GD. STUDY DESIGN AND
      SETTING: We conducted a prospective, multicenter cohort study of children (n =
      154) with GD treated with carbimazole for an intended duration of 24 +/- 3
      months. After the end of treatment, patients were followed up for at least 2 yr.
      The primary outcome was hyperthyroidism relapse. Cox's regression analysis was
      used and a prognostic score was constructed. RESULTS: The overall estimated
      relapse rate for hyperthyroidism was 59% (95% confidence interval 52-67%) at 1 yr
      and 68% (95% confidence interval 60-76%) at 2 yr after the end of treatment.
      Multivariate survival analysis showed that the risk of relapse was higher for
      patients of non-Caucasian origin [hazard ratio (HR) = 2.54, P < 0.001], with high
      serum thyroid-stimulating hormone receptor antibodies (HR = 1.21 by 10 U, P =
      0.03) and free T(4) (HR = 1.18 by 10 pmol/liter, P = 0.001) levels at diagnosis.
      Conversely, relapse risk decreased with increasing age at onset (HR = 0.74 per 5
      yr, P = 0.03) and duration of first course of ATD (HR = 0.57 per 12 months, P =
      0.005). A prognostic score was constructed, allowing the identification of three
      different risk groups, with 2-yr relapse rates of 46, 77, and 98%. CONCLUSIONS: A
      longer initial duration of euthyroid state with ATD seems to be the only variable
      related to the risk of hyperthyroidism relapse in children that can be
      manipulated. Ethnic origin, age, and severity of the disease at diagnosis may
      guide long-term disease management decisions.

PMID- 18628516
TI  - OTX2 mutation in a patient with anophthalmia, short stature, and partial growth
      hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1
      promoters.
AB  - CONTEXT: OTX2 is a transcription factor gene essential for eye development.
      Although recent studies suggest the involvement of OTX2 in pituitary function,
      there is no report demonstrating a positive role of OTX2 in the pituitary
      function. OBJECTIVE: The objective of the study was to report the results of
      functional studies indicating the relevance of OTX2 to pituitary function.
      PATIENT: A Japanese female patient with bilateral anophthalmia was found to have
      short stature (height, -3.3 sd) and isolated partial GH deficiency (peak serum GH
      3.1 and 9.7 mug/liter after insulin and arginine stimulations, respectively;
      serum IGF-I 37 ng/ml) at 3 yr 9 months of age. Magnetic resonance imaging
      delineated apparently normal pituitary gland. RESULTS: Mutation analysis showed a
      de novo heterozygous frameshift mutation (c.402insC) that is predicted to retain
      the homeodomain but lose the transactivation domain. Functional studies revealed
      that the wild-type and mutant OTX2 proteins localized to the nucleus and bound to
      the target sequences within the IRBP (interstitial retinoid-binding protein),
      HESX1 (HESX homeobox 1), and POU1F1 promoters. Furthermore, the wild-type OTX2
      protein markedly transactivated the promoters of IRBP ( approximately 27-fold),
      HESX1 ( approximately 4.5-fold), and POU1F1 ( approximately 19-fold), whereas the
      mutant OTX2 protein barely retained the transactivation activities and had no
      dominant-negative effects. CONCLUSIONS: The results provide direct evidence for
      OTX2 being involved in the pituitary function. It is likely that the heterozygous
      severe OTX2 loss-of-function mutation caused GH deficiency and short stature,
      primarily because of decreased transactivation function for HESX1 and POU1F1.

PMID- 18628517
TI  - Mitochondrial function in skeletal muscle is normal and unrelated to insulin
      action in young men born with low birth weight.
AB  - OBJECTIVE: Low birth weight (LBW) is an independent risk factor of insulin
      resistance and type 2 diabetes. Recent studies suggest that mitochondrial
      dysfunction and impaired expression of genes involved in oxidative
      phosphorylation (OXPHOS) may play a key role in the pathogenesis of insulin
      resistance in aging and type 2 diabetes. The aim of this study was to determine
      whether LBW in humans is associated with mitochondrial dysfunction in skeletal
      muscle. METHODS: Mitochondrial capacity for ATP synthesis was assessed by
      (31)phosphorus magnetic resonance spectroscopy in forearm and leg muscles in 20
      young, lean men with LBW and 26 matched controls. On a separate day, a
      hyperinsulinemic euglycemic clamp with excision of muscle biopsies and dual
      energy x-ray absorptiometry scanning was performed. Muscle gene expression of
      selected OXPHOS genes was determined by quantitative real-time PCR. RESULTS: The
      LBW subjects displayed a variety of metabolic and prediabetic abnormalities,
      including elevated fasting blood glucose and plasma insulin levels, reduced
      insulin-stimulated glycolytic flux, and hepatic insulin resistance. Nevertheless,
      in vivo mitochondrial function was normal in LBW subjects, as was the expression
      of OXPHOS genes. CONCLUSIONS: These data support and expand previous findings of
      abnormal glucose metabolism in young men with LBW. In addition, we found that the
      young, healthy men with LBW exhibited hepatic insulin resistance. However, the
      study does not support the hypothesis that muscle mitochondrial dysfunction per
      se is the underlying key metabolic defect that explains or precedes whole body
      insulin resistance in LBW subjects at risk for developing type 2 diabetes.

PMID- 18628518
TI  - Consequences of being born small for gestational age on body composition: an 8
      year follow-up study.
AB  - CONTEXT: Increased fat mass has been reported in children and adults born small
      for gestational age (SGA). However, the progression of anthropometric parameters
      have been poorly documented in SGA adults. OBJECTIVE: We hypothesized that SGA
      individuals would remain susceptible to gain more fat when adults beyond the
      period of postnatal catch-up growth. STUDY POPULATION AND DESIGN: From a
      community-based cohort, 389 subjects born full-term SGA (body weight < 10th
      percentile) were compared with 462 subjects born appropriate for gestational age
      (25th < body weight < 75th percentile). Anthropometric parameters were measured
      at 22 and 30 yr as well as body composition (by multifrequency bioelectrical
      impedancometry and skinfold thickness) at 30 yr. RESULTS: Both groups gained
      weight, body mass index (BMI), and waist circumference. Progression of BMI was
      significantly greater in SGA (1.8 +/- 2.6 vs. 1.4 +/- 2.6 kg/m(2); P = 0.03). At
      30 yr, the proportion of obese individuals was significantly increased in SGA
      (12.1 vs. 6.5%; P = 0.02), and percent body fat was significantly higher (23.5 +/
      8.7 vs. 21.9 +/- 8.0%; P = 0.01), the observation of which was confirmed by
      skinfold measures. Similarly, waist circumference gain was significantly greater
      in SGA (6.4 +/- 7.6 vs. 5.5 +/- 7.9, P = 0.04 when adjusted for gender and age).
      CONCLUSION: Over 8-yr follow-up, adults born SGA gained more BMI than appropriate
      for gestational age, resulting in greater fat mass with more abdominal fat. These
      data suggest that the consequences of fetal growth restriction on body
      composition are evolving beyond the period of early postnatal catch-up.

PMID- 18628519
TI  - Synergism between oral estrogen therapy and cytochrome P450 3A5*1 allele on the
      risk of venous thromboembolism among postmenopausal women.
AB  - CONTEXT: Hormone therapy increases the risk of venous thromboembolism (VTE) among
      postmenopausal women. This effect may be modulated by the expression of
      cytochromes P450 3A5 (CYP3A5) and 1A2 (CYP1A2) which are involved in the hepatic
      metabolism of estrogens. OBJECTIVE: The objective was to investigate the impact
      of CYP3A5 and CYP1A2 genetic polymorphisms on the association of VTE with hormone
      therapy. DESIGN: We conducted a case-control study. SETTING: This study was
      conducted in eight French hospital centers and in the general population.
      PATIENTS: CYP3A5 and CYP1A2 genotypes were evaluated among 195 cases with a first
      documented episode of idiopathic VTE and 533 controls matched for center, age,
      and admission date. OUTCOME MEASURE: The outcome measure was hormone therapy by
      route of estrogen administration. RESULTS: Overall, oral but not transdermal
      estrogen increased VTE risk [odds ratio (OR) = 4.5, 95% confidence interval (CI)
      = 2.6-7.6, and OR = 1.2, 95% CI = 0.8-1.8, respectively]. The allele frequency of
      CYP3A5*1 was 9 and 10% among cases and controls (OR = 1.0; 95% CI = 0.6-1.5) and
      that of CYP1A2*1F was 72 and 71% among cases and controls (OR = 1.5; 95% CI = 0.8
      2.8). Compared with nonusers, OR for VTE in users of oral estrogen was 3.8 (95%
      CI = 2.1-6.7) among patients without CYP3A5*1 allele and 30.0 (95% CI = 4.4
      202.9) among patients with this allele (test for interaction P = 0.04). By
      contrast, there was no significant interaction between CYP3A5*1 allele and
      transdermal estrogen on VTE risk. There is no interaction between CYP1A2 genetic
      polymorphism and hormone therapy on VTE risk. CONCLUSIONS: Women with CYP3A5*1
      allele using oral estrogen can define a subgroup at high VTE risk. Additional
      data are needed to assess the relevance of this genetic biomarker in the medical
      management of menopause.

PMID- 18628520
TI  - Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6
      phosphate dehydrogenase in patients with cortisone reductase deficiency.
AB  - CONTEXT: Cortisone reductase deficiency (CRD) is characterized by a failure to
      regenerate cortisol from cortisone via 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1), resulting in increased cortisol clearance, activation of the
      hypothalamic-pituitary-axis (HPA) and ACTH-mediated adrenal androgen excess.
      11beta-HSD1 oxoreductase activity requires the reduced nicotinamide adenine
      dinucleotide phosphate-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH)
      within the endoplasmic reticulum. CRD manifests with hyperandrogenism resulting
      in hirsutism, oligo-amenorrhea, and infertility in females and premature
      pseudopuberty in males. Recent association studies have failed to corroborate
      findings that polymorphisms in the genes encoding H6PDH (R453Q) and 11beta-HSD1
      (Intron 3 inserted adenine) interact to cause CRD. OBJECTIVE: Our objective was
      to reevaluate the genetics and steroid biochemistry of patients with CRD. DESIGN:
      We analyzed 24-h urine collection for steroid biomarkers by gas
      chromatography/mass spectrometry and sequenced the HSD11B1 and H6PD genes in our
      CRD cohort. PATIENTS: Patients included four cases presenting with
      hyperandrogenism and biochemical features clearly indicative of CRD. RESULTS: Gas
      chromatography/mass spectrometry identified steroid biomarkers that correlated
      with CRD in each case. Three cases were identified as homozygous (R109AfsX3,
      Y316X, and G359D) and one case identified as compound heterozygous (c.960G-->A
      and D620fsX3) for mutations in H6PD. No mutations affecting enzyme activity were
      identified in the HSD11B1 gene. Expression and activity assays demonstrate loss
      of function for all reported H6PDH mutations. CONCLUSIONS: CRD is caused by
      inactivating mutations in the H6PD gene, rendering the 11beta-HSD1 enzyme unable
      to operate as an oxoreductase, preventing local glucocorticoid regeneration.
      These data highlight the importance of the redox control of cortisol metabolism
      and the 11beta-HSD1-H6PDH pathway in regulating hypothalamic-pituitary-adrenal
      axis activity.

PMID- 18628521
TI  - Increased protein turnover and proteolysis is an early and primary feature of
      short-term experimental hyperthyroidism in healthy women.
AB  - CONTEXT: Hyperthyroidism increases energy expenditure, glucose turnover,
      lipolysis, and protein breakdown. OBJECTIVE: Our objective was to test whether
      increased protein breakdown occurs independently of other catabolic effects in
      mild experimental hyperthyroidism. DESIGN: We conducted a single-blind,
      randomized, placebo-controlled, crossover study. Protein dynamics of the whole
      body and of the forearm muscles were measured by amino acid tracer dilution
      technique ([(15)N]phenylalanine and [(2)H(4)]tyrosine). All subjects underwent a
      3-h study in the basal state followed by a 3-h euglycemic clamp study. SETTING:
      The study took place at a university clinical research unit. PARTICIPANTS: Eight
      healthy women (24-46 yr old) participated. INTERVENTION: Intervention included 6
      d thyroid hormone (T(4) 50 microg and T(3) 0.67 microg/kg.d) or placebo
      administration. RESULTS: Thyroid hormone administration led to mild T(3)
      hyperthyroidism with more than a doubling of T(3) levels and suppression of TSH.
      Energy expenditure and body composition was unchanged. Glucose infusion rates,
      forearm glucose uptake, and levels of lipid intermediates were also alike. Basal
      whole-body phenylalanine flux and tyrosine flux (reflecting whole-body protein
      breakdown) were increased (P < 0.05) as were whole-body protein synthesis rate (P
      = 0.05). Basal forearm rate of appearance and disappearance for phenylalanine
      (reflecting muscle protein breakdown and synthesis) were similar. CONCLUSIONS:
      Mild short-term experimental hyperthyroidism increases whole-body protein
      turnover and breakdown before any measurable changes in energy expenditure or
      glucose and fat metabolism, suggesting that amino acid and protein metabolism is
      an early and primary target for thyroid hormone action in humans.

PMID- 18628522
TI  - Endocrine manifestations of the rapid-onset obesity with hypoventilation,
      hypothalamic, autonomic dysregulation, and neural tumor syndrome in childhood.
AB  - CONTEXT: Rapid-onset obesity with hypoventilation, hypothalamic, autonomic
      dysregulation, and neural tumor (ROHHADNET) is a newly described syndrome that
      can cause cardiorespiratory arrests and death. It mimics several endocrine
      disorders or genetic obesity syndromes during early childhood and is associated
      with various forms of hypothalamic-pituitary endocrine dysfunctions that have not
      yet been fully investigated. OBJECTIVE: The current report aspires to facilitate
      the earlier recognition and appropriate treatment of the ROHHADNET syndrome when
      children present with various endocrine manifestations, such as early obesity,
      growth failure, pseudo-Cushing's syndrome, glucocorticoid insufficiency,
      congenital hypopituitarism, or adrenal tumors. A more widespread knowledge of the
      syndrome will help characterize its molecular origin. DESIGN: Endocrine studies
      were performed in six patients admitted for seemingly common early-onset obesity
      associated with growth failure in five of them. The six patients later showed
      distinctive features of the ROHHADNET syndrome. RESULTS: Abnormalities of the
      pituitary adrenal axis ranged from a true Cushing-like profile (one of six), to
      glucocorticoid deficiency with normal ACTH (two of six). Complete GH deficiency
      with low IGF-I was observed in four of six, hypogonadotropic hypogonadism in four
      of six, hyperprolactinemia in six of six, and various degrees of TSH/T(4)
      abnormalities in five of five patients. All had increased natremia without
      diabetes insipidus. Five children had unilateral macroscopic adrenal
      ganglioneuroma. Two patients died at 8.5 and 12 yr of age. CONCLUSIONS: Various
      hypothalamic-pituitary endocrine dysfunctions are associated with ROHHADNET,
      carrying a risk of misdiagnosis until other elements of the syndrome make it more
      easily recognizable. Given its severity, ROHHADNET syndrome should be considered
      in all cases of isolated, rapid, and early obesity.

PMID- 18628523
TI  - Zinc transporter-8 gene (SLC30A8) is associated with type 2 diabetes in Chinese.
AB  - CONTEXT: Several genome-wide association studies identified a strong association
      of SLC30A8 with type 2 diabetes in individuals of European ancestry. The effect
      of the association of rs13266634 with type 2 diabetes or related glycemic traits
      has not been fully extended to non-European populations, and a comprehensive
      examination of common variants in the gene has not yet been carried out in Han
      Chinese. OBJECTIVE: The objective of the study was to investigate the association
      of SLC30A8 with type 2 diabetes in Chinese. DESIGN: A comprehensive gene-based
      association study was performed using 14 tagging single-nucleotide polymorphism
      (SNPs) of SLC30A8 in Han Chinese subjects with normal glucose tolerance (NGT; n =
      721), impaired glucose regulation (IGR; n = 375), and type 2 diabetes (n = 521).
      RESULTS: A significant association for SNP rs13266634 was observed between
      patients with type 2 diabetes and NGT controls (P = 0.016). The association was
      also observed between combined type 2 diabetes/IGR and NGT subjects (P = 0.002).
      The adjusted odds ratios for homozygote CC vs. TT at this locus were 1.71 for
      type 2 diabetes (95% confidence interval 1.19-2.45, P = 0.002) and 1.77 for type
      2 diabetes and IGR (95% confidence interval 1.29-2.42, P = 0.0001). We further
      studied the genotype-phenotype correlation in 70 Han Chinese using iv glucose
      tolerance test and found an association between SNP rs13266634 and acute insulin
      response to glucose and disposition index (adjusted P = 0.012 and 0.004,
      respectively). CONCLUSIONS: Our results provide evidence that SLC30A8 is a
      susceptible locus for type 2 diabetes in Chinese population, and its variant can
      influence insulin secretion.

PMID- 18628524
TI  - Patterns of alcohol consumption and the metabolic syndrome.
AB  - CONTEXT AND OBJECTIVE: Protective and detrimental associations have been reported
      between alcohol consumption and the metabolic syndrome. This may be due to
      variations in drinking patterns and different alcohol effects on the metabolic
      syndrome components. This study is designed to examine the relationship between
      alcohol consumption patterns and the metabolic syndrome. DESIGN, SETTING,
      PARTICIPANTS, AND MEASURES: The 1999-2002 National Health and Nutrition
      Examination Survey is a population-based survey of noninstitutionalized U.S.
      adults. Current drinkers aged 20-84 yr without cardiovascular disease who had
      complete data on the metabolic syndrome and drinking patterns were included in
      the analysis (n = 1529). The metabolic abnormalities comprising the metabolic
      syndrome included having three of the following: impaired fasting
      glucose/diabetes mellitus, high triglycerides, abdominal obesity, high blood
      pressure, and low high-density-lipoprotein cholesterol. Measures of alcohol
      consumption included usual quantity consumed, drinking frequency, and frequency
      of binge drinking. RESULTS: In multinomial logistic regression models controlling
      for demographics, family history of cardiovascular disease and diabetes, and
      lifestyle factors, increased risk of the metabolic syndrome was associated with
      daily consumption that exceeded U.S. dietary guideline recommendations (more than
      one drink per drinking day for women and more than two drinks per drinking day
      for men (odds ratio 1.60, 95% confidence interval 1.22-2.11) and binge drinking
      once per week or more [odds ratio (95% confidence interval) 1.51 (1.01-2.29]. By
      individual metabolic abnormality, drinking in excess of the dietary guidelines
      was associated with an increased risk of impaired fasting glucose/diabetes
      mellitus, hypertriglyceridemia, abdominal obesity, and high blood pressure.
      CONCLUSION: Public health messages should emphasize the potential cardiometabolic
      risk associated with drinking in excess of national guidelines and binge
      drinking.

PMID- 18628525
TI  - Urban tropospheric ozone increases the prevalence of vitamin D deficiency among
      Belgian postmenopausal women with outdoor activities during summer.
AB  - CONTEXT: By absorbing sunlight UVB and thereby reducing cutaneous vitamin D
      photosynthesis, ozone, a common urban pollutant, could cause hypovitaminosis D.
      OBJECTIVES: The objective of the study was to establish the characteristics and
      percentage of subjects with serum 25-hydroxyvitamin D [25(OH)D] less than 75
      nmol/liter among postmenopausal women engaging in outdoor activities in either
      Brussels or the countryside. DESIGN/SETTING: This was a cross-sectional study
      conducted in a university research hospital. PATIENTS/METHODS: Among 249 women
      consulting for either shoulder tendonitis or lumbar spine osteoarthritis, 121
      free of conditions and drugs affecting bone and calcium metabolism completed two
      food-frequency questionnaires within 15 d and we selected the 85 subjects with
      retest scores within the +/- 15% of test scores. Other parameters included sun
      exposure index (SEI), PTH levels, and femoral neck T-score. RESULTS: Urban
      residents (n = 38) and rural residents (n = 47) did not differ in mean ages, body
      mass indices, and vitamin D intakes. When compared with rural inhabitants, urban
      inhabitants were exposed to ozone levels 3 times higher, and despite a higher
      mean SEI (113 vs. 87; P < 0.001), they had a higher prevalence of 25(OH)D less
      than 75 nmol/liter (84 vs. 38%). After adjusting for SEI, 25(OH)D was 2-fold
      higher in rural residents, and after adjusting for 25(OH)D, SEI was 3-fold higher
      in urban residents. Femoral neck T-scores correlated positively with 25(OH)D and
      negatively with PTH levels. CONCLUSIONS: Air pollution may be a neglected risk
      factor for hypovitaminosis D, which is known to compromise several health
      outcomes. As long as 25(OH)D is greater than 75 nmol/liter, calcium intakes
      greater than 17.5 mmol/d are unnecessary to prevent elevations in PTH levels.

PMID- 18628526
TI  - Production of interleukin-1alpha by human endometrial stromal cells is triggered
      during menses and dysfunctional bleeding and is induced in culture by epithelial
      interleukin-1alpha released upon ovarian steroids withdrawal.
AB  - CONTEXT: Endometrial breakdown during menstruation and dysfunctional bleeding is
      triggered by the abrupt expression of matrix metalloproteinases (MMPs), including
      interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal
      cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However,
      the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha
      expression and bioactivity remains unknown. OBJECTIVE AND DESIGN: Variations of
      endometrial IL-1alpha mRNA and protein along the menstrual cycle and during
      dysfunctional bleeding were determined using RT-PCR, in situ hybridization, and
      immunolabeling. The mechanism of EP control was analyzed using culture of
      explants, laser capture microdissection, and purified cells. Data were compared
      with expression changes of IL-1beta and IL-1 receptor antagonist. RESULTS: IL
      1alpha is synthesized by epithelial cells throughout the cycle but E and/or P
      prevents its release. In contrast, endometrial stromal cells produce IL-1alpha
      only at menses and during irregular bleeding in areas of tissue breakdown.
      Stromal expression of IL-1alpha, like that of MMP-1, is repressed by P (alone or
      with E) but triggered by epithelium-derived IL-1alpha released upon EP
      withdrawal. CONCLUSIONS: Our experiments in cultured endometrium suggest that IL
      1alpha released by epithelial cells triggers the production of IL-1alpha by
      stromal cells in a paracrine amplification loop to induce MMP-1 expression during
      menstruation and dysfunctional bleeding. All three steps of this amplification
      cascade are repressed by EP.

PMID- 18628527
TI  - Selective loss of MEG3 expression and intergenic differentially methylated region
      hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning
      pituitary adenomas.
AB  - CONTEXT: MEG3 is an imprinted gene encoding a novel noncoding RNA that suppresses
      tumor cell growth. Although highly expressed in the normal human pituitary, it is
      unknown which of the normal pituitary cell types and pituitary tumors express
      MEG3. OBJECTIVES: Our objectives were 1) to investigate cell-type- and tumor-type
      specific expression of MEG3 in the human pituitary and 2) to investigate whether
      methylation in the intergenic differentially methylated region (IG-DMR) at the
      DLK1/MEG3 locus is involved in the loss of MEG3 expression in tumors. DESIGN AND
      METHODS: RT-PCR, quantitative RT-PCR, Northern blot, and a combination of in situ
      hybridization and immunofluorescence were used to determine the cell-type- and
      tumor-type-specific MEG3 expression. Bisulfite treatment and PCR sequencing of
      genomic DNA were used to measure the CpG methylation status in the normal and
      tumor tissues. Five normal human pituitaries and 17 clinically nonfunctioning, 11
      GH-secreting, seven prolactin-secreting, and six ACTH-secreting pituitary
      adenomas were used. RESULTS: All normal human pituitary cell types express MEG3.
      However, loss of MEG3 expression occurs only in nonfunctioning pituitary adenomas
      of a gonadotroph origin. All other pituitary tumor phenotypes examined express
      MEG3. Hypermethylation of the IG-DMR at the DLK1/MEG3 locus is present in
      nonfunctioning pituitary adenomas. CONCLUSIONS: MEG3 is the first human gene
      identified expressed in multiple normal human pituitary cell types with loss of
      expression specifically restricted to clinically nonfunctioning pituitary
      adenomas. The IG-DMR hypermethylation may be an additional mechanism for MEG3
      gene silencing in such tumors.

PMID- 18628528
TI  - Association of low sodium-iodide symporter messenger ribonucleic acid expression
      in malignant thyroid nodules with increased intracellular protein staining.
AB  - CONTEXT: The expression of sodium iodide symporter (NIS) is required for iodide
      uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide
      uptake. However, previous studies by RT-PCR or immunohistochemistry have shown
      divergent results of NIS expression in these nodules. OBJECTIVE: The objective of
      the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH
      receptor proteins expression, and localize the NIS protein in thyroid nodules
      samples and their surrounding nonnodular tissues (controls). DESIGN: NIS mRNA
      levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins,
      evaluated by immunohistochemistry, were examined in surgical specimens of 12
      benign and 13 malignant nodules and control samples. RESULTS: When compared with
      controls, 83.3% of the benign and 100% of the malignant nodules had significantly
      lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant
      nodules had stronger intracellular NIS immunostaining than controls. Low gene
      expression associated with strong intracellular immunostaining was most
      frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS
      protein was located at the basolateral membrane in 24% of the control samples,
      8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign
      nodules with strong TSH receptor positivity (41.6%) was higher than malignant
      (7.7%). CONCLUSION: We confirmed that reduced NIS mRNA expression in thyroid
      malignant nodules is associated with strong intracellular protein staining and
      may be related to the inability of the NIS protein to migrate to the cellular
      basolateral membrane. These results may explain the low iodide uptake of
      malignant nodules.

PMID- 18628529
TI  - The effect of strength and endurance training on insulin sensitivity and fat
      distribution in human immunodeficiency virus-infected patients with
      lipodystrophy.
AB  - CONTEXT: Fat redistribution, insulin resistance, and low-grade inflammation
      characterize HIV-infected patients with lipodystrophy. Currently, no effective
      therapies exist for the combined treatment of fat redistribution and insulin
      resistance. OBJECTIVE: Our objective was to evaluate the effects of strength and
      endurance training on insulin sensitivity and fat distribution in HIV-infected
      patients with lipodystrophy. SUBJECTS AND METHODS: Twenty sedentary HIV-infected
      men with lipodystrophy were randomly assigned to supervised strength or endurance
      training three times a week for 16 wk. The primary endpoints were improved
      peripheral insulin sensitivity (euglycemic-hyperinsulinemic clamp combined with
      isotope-tracer infusion) and body fat composition (dual-energy x-ray
      absorptiometry scan). Secondary endpoints included fasting lipids and
      inflammatory markers. RESULTS: Insulin-mediated glucose uptake increased with
      both endurance training (55.7 +/- 11 to 63.0 +/- 11 micromol glucose/kg lean
      mass.min, P = 0.02) and strength training (49.0 +/- 12 to 57.8 +/- 18 micromol
      glucose/kg lean mass.min, P = 0.005), irrespective of training modality (P =
      0.24). Only strength training increased total lean mass 2.1 kg [95% confidence
      interval (CI), 0.8-3.3], decreased total fat 3.3 kg (95% CI, -4.6 to -2.0), trunk
      fat 2.5 kg (95% CI, -3.5 to -1.5), and limb fat 0.75 kg (95% CI, -1.1 to -0.4).
      Strength training significantly decreased total and limb fat mass to a larger
      extent than endurance training (P < 0.05). Endurance training reduced total
      cholesterol, low-density lipoprotein cholesterol, free fatty acids, high
      sensitivity C-reactive protein, IL-6, IL-18, and TNF-alpha and increased high
      density lipoprotein cholesterol, whereas strength training decreased
      triglycerides, free fatty acids, and IL-18 and increased high-density lipoprotein
      cholesterol (P < 0.05 for all measurements). CONCLUSION: This study demonstrates
      that both strength and endurance training improve peripheral insulin sensitivity,
      whereas only strength training reduces total body fat in HIV-infected patients
      with lipodystrophy.

PMID- 18628531
TI  - Malabsorption in wasting HIV disease: diagnostic and management issues in
      resource-poor settings.

PMID- 18628532
TI  - A risk assessment for pregnancy using the World Health Organization classifying
      form in primary health-care facilities in Enugu, Nigeria.
AB  - We present a cross-sectional survey of the pattern of high-risk pregnancies in
      randomly selected primary health-care facilities in Enugu, Nigeria, using the
      World Health Organization's classifying form. None of the 10 maternity homes
      studied had a standard risk screening tool. The age of the 299 women studied
      ranged from 16 to 42 years with a mean of 27.8 +/- 6.7 years. Eighty-eight
      (29.4%) of them were nulliparous, 160 (53.5%) were multiparous and 51 (17.1%)
      grandmultiparous. One hundred and twenty (40.1%) respondents were in the high
      risk category. Rhesus D-negative blood group parturients (42, 35.0%), previous
      perinatal deaths (29.2%) and multiple pregnancies (9.2%) were the most common
      risk factors. The prevalence of high-risk pregnancies significantly increased
      with maternal age and parity and was not influenced by an improved maternal
      educational attainment. The institution of screening for high-risk pregnancies is
      vital at the primary health-care level and must be emphasized and must be
      regularly audited.

PMID- 18628530
TI  - Incretin-based therapies in type 2 diabetes mellitus.
AB  - CONTEXT: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic
      polypeptide are incretins secreted from enteroendocrine cells postprandially in
      part to regulate glucose homeostasis. Dysregulation of these hormones is evident
      in type 2 diabetes mellitus (T2DM). Two new drugs, exenatide (GLP-1 mimetic) and
      sitagliptin [dipeptidyl peptidase (DPP) 4 inhibitor], have been approved by
      regulatory agencies for treating T2DM. Liraglutide (GLP-1 mimetic) and
      vildagliptin (DPP 4 inhibitor) are expected to arrive on the market soon.
      EVIDENCE ACQUISITION: The background of incretin-based therapy and selected
      clinical trials of these four drugs are reviewed. A MEDLINE search was conducted
      for published articles using the key words incretin, glucose-dependent
      insulinotropic polypeptide, GLP-1, exendin-4, exenatide, DPP 4, liraglutide,
      sitagliptin, and vildagliptin. EVIDENCE SYNTHESIS: Exenatide and liraglutide are
      injection based. Three-year follow-up data on exenatide showed a sustained weight
      loss and glycosylated hemoglobin (HbA(1c)) reduction of 1%. Nausea and vomiting
      are common. Results from phase 3 studies are pending on liraglutide. Sitagliptin
      and vildagliptin are orally active. In 24-wk studies, sitagliptin reduces HbA(1c)
      by 0.6-0.8% as monotherapy, 1.8% as initial combination therapy with metformin,
      and 0.7% as add-on therapy to metformin. Vildagliptin monotherapy lowered HbA(1c)
      by 1.0-1.4% after 24 wk. Their major side effects are urinary tract and
      nasopharyngeal infections and headaches. Exenatide and liraglutide cause weight
      loss, whereas sitagliptin and vildagliptin do not. CONCLUSIONS: The availability
      of GLP-1 mimetics and DPP 4 inhibitors has increased our armamentarium for
      treating T2DM. Unresolved issues such as the effects of GLP-1 mimetics and DPP 4
      inhibitors on beta-cell mass, the mechanism by which GLP-1 mimetics lowers
      glucagon levels, and exactly how DPP 4 inhibitors lead to a decline in plasma
      glucose levels without an increase in insulin secretion, need further research.

PMID- 18628533
TI  - Baseline assessment of collaborative tuberculosis/HIV activities in Kinshasa, the
      Democratic Republic of Congo.
AB  - Ninety-two clinics were surveyed in 2005 as part of a baseline assessment of HIV
      activities in Tuberculosis (TB) clinics in Kinshasa, Democratic Republic of
      Congo. Some HIV activities were implemented in 58% of TB clinics. The majority of
      health had > or = 1 health care worker (HCW) trained in either HIV counseling or
      testing (71%). Fifty-three clinics offered counseling and testing to TB patients;
      twenty-two (42%) routinely offered HIV CT to all patients, while others used
      selective criteria. While most offered on-site counseling (92%) and testing
      (77%), not all 53 clinics had a HCW trained in counseling and only 31 had access
      to a counseling room. Cotrimoxazole prophylaxis was offered in 51% of clinics;
      antiretroviral treatment in 17%. Shortcomings in human resources, infrastructure
      and quality of services were revealed. Strengthening those clinics already
      implementing HIV activities could be prioritized to achieve the goals set forward
      by the Global Plan to Stop TB.

PMID- 18628534
TI  - Rotational rural surgery for the poor in developing countries.
AB  - Radio and television announcements advised patients with surgical problems in the
      rural areas of Osun State, Nigeria, to report at any of the nine zonal
      headquarters of the state which were closest to their homes in order to receive
      free treatment. Over 1000 patients reported and 801 received operations on a
      rotational basis within nine weeks. We studied 719 of these patients, ages
      between 4 months and 87 years, who had detailed follow-up records. There were 14
      different procedures ranging from a hernia repair to the separation of
      syndactyly. Complications included postoperative pain, haematoma and late
      superficial wound infection. We concluded that rotational free surgery can help
      the poor in the third-world countries to receive treatment that they would
      otherwise not be able to afford.

PMID- 18628535
TI  - HIV and obstetric complications and fetal outcomes in Vellore, India.
AB  - Antenatal prevalence is more than 1% in parts of India, yet little is known about
      the complications and fetal outcomes in this region. We reviewed the records of
      23,386 women who delivered at the Christian Medical College Hospital in Vellore,
      India from 2000 through 2002. HIV-infected women were more likely than HIV
      uninfected women to have pregnancy-induced hypertension, anaemia, breech
      presentations, stillborn babies and fetal deaths. HIV-infected women who did not
      receive mother-to-child transmission prophylaxis or had breech fetal presentation
      were more likely to have fetal deaths (P = 0.001). HIV prophylaxis and optimal
      prenatal care should be a priority for HIV-infected pregnant women in resource
      limited countries.

PMID- 18628536
TI  - Exploring the pattern of complications of induced abortion in a rural mission
      tertiary hospital in the Niger Delta, Nigeria.
AB  - Unsafe abortion remains a major cause of maternal morbidity and mortality in
      developing countries including Nigeria. We report a 10-year descriptive review of
      118 consecutive cases of complicated induced abortions. At our centre,
      complications of induced abortion constituted 2.3% of maternal admissions, 5.6%
      of gynaecological admissions and 22.6% of maternal deaths. Fifty-nine percent of
      the women were married and the mean age was 25.6 +/- 7.9 years. Doctors performed
      51.7% of the induced abortion and nurses performed 13.9%. Of the mortalities,
      medical doctors did 61 of the abortions in which 18 died (29.5%); traditional
      medical practitioners were responsible for 13 of the abortions in which two died
      (15.4%); of the 16 abortions performed by nurses, two died (12.5%). Sepsis was
      the most common cause of death (73%). There is an urgent need to improve the
      knowledge and utilization of modern contraception by rural women in order to
      prevent unwanted pregnancies. Doctors need to be continuously trained inn the
      basic principles of postabortion care.

PMID- 18628537
TI  - Non-doctor anaesthesia in Nepal: developing an essential cadre.
AB  - Nepal is a mountainous country of 27 million people where the widespread lack of
      access to operative services is a major cause of morbidity and mortality. One
      critical reason for this is the lack of trained, appropriately distributed
      anaesthesia providers. We discuss the evolution of the 'anaesthesia assistant' in
      Nepal, review the international literature concerning the development of non
      doctor anaesthetists, and invite links with others working in this field.

PMID- 18628538
TI  - Traditional medicine, delays and hospital mortality of children under five years
      of age in the rural district of Kigoma, western Tanzania: an observational
      hospital-based study.
AB  - The use of traditional medicine in the treatment of 596 children aged 0-60 months
      before admission was common (41.4 %). Children were more likely to die if they
      had first been treated with traditional medicine (50/244; 20.5% vs 29/342; 8.5%)
      or were younger (median 9 vs 12 months old.) Children who had received
      traditional medicine were younger (median 11 vs. 13 months), came later for
      hospital treatment (median three vs. five days), had a longer journey on foot to
      reach the health centre (3.4 vs. 2.9 h), and died from common diseases and not
      from an obvious toxic syndrome.

PMID- 18628539
TI  - Histopathology slide projector: a simple improvisation.
AB  - The ability to examine histopathology and other hematological slides under
      microscope is a necessary and important service which should be available in
      every health facility. The slides need to be projected on to a screen. We
      describe an inexpensive and easily constructed technique for projecting magnified
      images of slides using a simple microscope. It is effective both for making
      observations and for use as a teaching aid.

PMID- 18628540
TI  - The proctoscope.
AB  - A cheaper version of a self-illuminated proctoscope which suitable for use in
      developing countries designed for diagnosis and intervention in anorectal
      diseases is described.

PMID- 18628541
TI  - Hyponatraemia and hypokalaemia in adults with uncomplicated malaria in Thailand.
AB  - In a retrospective study of 1415 patients aged 15 and over, we determined the
      incidence of clinically important hyponatraemia and hypokalaemia in adults with
      uncomplicated malaria. On admission, serum concentrations of sodium (135-145
      mmol/L) and potassium (3.5-5.0 mmol/L) were found outside these reference ranges
      in 81% of patients. Severe hypokalaemia (K+ <3.0 mmol/L) and severe hyponatraemia
      (Na+ <125 mmol/L occurred in 4.4% and 0.6% of the patients, respectively. For
      hypokalaemia (43%) and hyponatraemia (37%), hypovolaemia, blood urea to
      creatinine ratio and high serum glucose (>100 mg/dL) were all independent factors
      (P < 0.001). Other independent predictors for hypokalaemia were Plasmodium vivax
      infection, female gender; and for hyponatraemia, P. falciparum infection, male
      gender, concentrations of G-6-PD and serum bicarbonate.

PMID- 18628542
TI  - Prevalence of depressive symptoms among Nigerian medical undergraduates.
AB  - This study assessed the epidemiology of depressive symptoms in Nigerian medical
      students. A cross-sectional study of 262 medical students from University of
      Nigeria, Enugu campus, one of the foremost medical schools in Nigeria was
      studied. Data were collected using structured self-administered questionnaires
      and the Zung self-rating depression scale developed by Zung as an instrument,
      which measures the subjective experience of depression. The age range of students
      was 16-30 years. The prevalence of depression among the students was 23.3%.
      Students aged 16-20, females, and those who had a professional examination during
      the period of the study had higher levels of depression, although these findings
      were not significant. However, students who smoked regularly had significantly
      higher levels of depression than those who did not smoke. Medical educators in
      Nigeria need to be aware of the vulnerability of medical students to depression.

PMID- 18628543
TI  - World Health Organization Clinical Stage 3 disease conditions in HIV-infected
      patients who start antiretroviral therapy in Malawi.
AB  - There is little information about disease conditions that are diagnosed in
      patients diagnosed as having World Health Organization Clinical Stage 3 HIV who
      are started on antiretroviral therapy (ART) in Africa. We therefore conducted an
      audit in the central region of Malawi of patients registered for ART between
      January and September 2006. There were 4299 patients in Stage 3 of whom 4154 had
      data about their disease conditions. Only one condition was listed for 3880
      patients. Of these, 1892 (48.8%) had unexplained weight loss, chronic fever or
      chronic diarrhoea, 822 (21.2%) had active/previous tuberculosis (TB) and 671
      (17.3%) had a severe presumed bacterial infection. No patient was diagnosed as
      having haematological abnormalities. Nearly half the patients started on ART had
      a symptomatic, unspecified disease, (which may be obscuring important pathologies
      such as TB) and almost no laboratory assessment had taken place before the
      commencement of ART. These two areas need to be addressed in order to improve the
      management of patients starting on ART.

PMID- 18628544
TI  - Quality of life for families with spina bifida in Kenya.
AB  - Spina bifida (SB) affects children worldwide. Studies from developed nations have
      explored the impact of SB on the quality of life of children and their parents.
      However, there are no such studies available from developing countries. We have
      therefore undertaken to document the impact of the disability on the families of
      affected children in Kenya. A questionnaire was administered to 40 mothers and
      their children, who were receiving treatment for SB at our institution. The
      results of this study should indicate where community and governmental resources
      and educational efforts for the disabled should be directed.

PMID- 18628545
TI  - An audit of obstetric fistulae in a teaching hospital in South Africa.
AB  - Obstetric fistulae are still common in the rural areas of South Africa. This
      study describes the demographic and clinical characteristics of 41 women with
      obstetric urinary fistulae. All were from poor socioeconomic backgrounds and had
      limited or no access to antenatal care.

PMID- 18628546
TI  - Postmortem trucut transnasal brain biopsy in the diagnosis of encephalitis.
AB  - Diagnosing encephalitis is often difficult with a definitive diagnosis being
      reached at best in only 40% of cases. This clinical condition is associated with
      a high morbidity and mortality. A brain biopsy is the gold standard for the
      diagnosis of this disease. However, this procedure is rarely done, resulting in
      the cause of death being largely speculative. We propose a simple procedure for
      postmortem brain biopsy through the transnasal transcribriform route that will
      possibly be more acceptable to clinicians and relatives alike due to lack of
      external disfigurement, relative ease of the procedure and economy of time and
      manpower. This could also prove to be of immense benefit in an epidemic of
      encephalitis, especially in remote areas.

PMID- 18628547
TI  - Haemolytic uraemic syndrome in children admitted to a rural district hospital in
      Kenya.
AB  - We studied children admitted to Kilifi District Hospital, Kenya, between 1997 and
      2005 with haemolytic uraemic syndrome (HUS) and reviewed their records in order
      to determine the clinical features and outcomes of the disease. Thirty-one
      children fulfilled the criteria: 21 (68%) had diarrhoea-associated HUS (D + HUS),
      the remainder did not (D-HUS); five had involvement of the central nervous
      system. Those with D-HUS had lower haemoglobin and platelet counts when compared
      with those with D + HUS. The overall mortality rate was 55% (17/31) with no
      significant difference between the two groups. Severe hyponatraemia ([Na(+)] <120
      mmol/L) predicted a poor outcome. Shigella dysenteriae was the most common
      isolated organism in the stool and Escherichia coli and S. dysenteriae were the
      most common blood isolates. HUS carries a high mortality rate and D-HUS is as
      common as D + HUS.

PMID- 18628548
TI  - Frontoethmoidal meningoencephalocoele repair in Cambodia: outcomes and cost
      comparisons.
AB  - In Cambodia, spina bifida is rare, but frontoethmoidal meningoencephalocoeles
      (MECs) are common. Mean life expectancy for patients with congenital MECs may be
      <20 years, but the complex treatment required has not been available in the
      country until recently. During visits by combined neurosurgical/craniofacial
      teams from both Germany and France, a method of repair has been developed that is
      suitable for the local conditions, affordable and has allowed Cambodian surgeons
      to learn how to successfully treat MECs. The surgical technique and initial
      results with 30 patients have been described in a previous publication. This
      paper presents the outcomes of 128 cases and illustrates that it is cost
      effective for these patients to be treated in Cambodia.

PMID- 18628549
TI  - The unreported morbidity of suicidal poisonings during an insurgency: a 16-year
      Kashmir experience.
AB  - Around a million people commit suicide, and at least 10 times this number attempt
      suicide, worldwide every year. No nationwide epidemiological studies have been
      undertaken in India but a significant rise in suicides has been observed in
      Kashmir in recent years. This study was carried out on patients reporting to the
      Government SMHS Hospital in Srinagar with a history of suicidal poisoning.

PMID- 18628550
TI  - Prevalence of opportunistic infections in AIDS patients in Mangalore, Karnataka.
AB  - A study was conducted to determine the prevalence of opportunistic infections in
      HIV-seropositive patients at Kasturba Medical College Hospital, Mangalore. Three
      hundred and seven HIV-positive patients were screened for various opportunistic
      pathogens. Tuberculosis was the most common infection followed by candidiasis,
      cryptosporidiosis and cryptococcal meningitis.

PMID- 18628551
TI  - Paralytic poliomyelitis during the pre-, peri- and post-suspension periods of a
      polio immunization campaign.
AB  - A total of 744 paralytic poliomyelitis patients (0-59 months old) were reviewed
      and results showed a critical and perpetual surge during 2003 (20.2%), 2004
      (27.4%) and 2005 (41%). A slight male predominance (56%) was reported and a high
      incidence was reported in the low socioeconomic (68.3%) and urban setting (60.3%)
      groups. It was concluded that the polio eradication campaigning programmes in
      Nigeria had not been successful and that legislation on poliomyelitis was
      required.

PMID- 18628552
TI  - Clinico-laboratory findings of patients during dengue outbreak from a tertiary
      care hospital in Delhi.
AB  - There are outbreaks of dengue every year in India. They vary in the predominant
      serotype involved, clinical features and predominant laboratory findings. This
      study of the 2006 outbreak in Delhi highlights clinical features and laboratory
      parameters of dengue cases and compares the clinical features among the adult and
      paediatric age groups. The 2006 outbreak had higher bleeding manifestations and a
      greater involvement of the adult male population than in previous outbreaks. No
      correlation was observed between platelet count and different bleeding
      manifestations until they dropped <20,000 per microL. Few patients developed a
      florid picture before seroconversion, highlighting a greater stress on the
      haematological rather than immunological profile of such patients. Atypical
      symptoms, such as diarrhoea, menorrhagia and seizures were often the presenting
      complaints rather than the typical clinical features of dengue.

PMID- 18628553
TI  - Neurocysticercosis in a north Indian hospital.
AB  - In endemic regions, neurocysticercosis (NCC) is the most commonly diagnosed
      parasitic disease of the central nervous system, and the most common cause of
      convulsions and hydrocephalus in adults. During January 2000-December 2006, serum
      samples collected from patients presenting with various manifestations with a
      clinical diagnosis of cysticercosis and/or relevant computed tomography findings
      were subjected to an enzyme-linked immunosorbent assay test for NCC. Anti
      cysticercus antibodies were detected in 155 of the 1096 (14.1%) cases.
      Generalized seizure (33.9%) was the most common presenting symptom. Solitary
      lesion (74.2%) was the most common radiological finding. This study provides an
      assessment of the epidemiology of NCC in Delhi and stresses the need for its
      prevention.

PMID- 18628554
TI  - Intra-family transmission of Vibrio cholerae during a cholera epidemic in rural
      south-southern Nigeria.

PMID- 18628555
TI  - The sixteen-year trend of syphilis in Turkey: data from blood donors.
AB  - This study was conducted in order to determine the prevalence and trends of
      antibodies to syphilis among Turkish blood donors (BDs) at the 22 National Blood
      Transfusion Service, Kizilay, between 1989 and 2004. Among the 6,240,130 BDs, a
      reactive result was obtained with the rapid plasma reagin test for 6864 donors
      (0.11%). A serious increasing trend was observed between 1989 and 1992
      (41/100.000 versus 92/100.000 cases, P = 0.003, CI 95, 33-107), in 1998, the
      rates were observed to have increased approximately 4.01 times compared with that
      of 1989 (41/100,000 versus 168/000,000, P = 0.001, CI 95, 28-183). After 2002,
      syphilis seropositivity showed a marked decreasing trend (P = 0.002, CI 95, 36
      118). However, as this survey shows, the rate of seropositive donors for syphilis
      has been greatly reduced but it is believed that a more thorough management
      strategy is necessary in order to cause a further reduction in Turkey.

PMID- 18628556
TI  - Seroprevalence of human immunodeficiency virus among blood donors in a rural
      Ethiopian hospital.
AB  - We describe our experience of the HIV seroprevalence among blood donors in a
      rural general hospital in Ethiopia during an eight-year period (January 1998
      December 2006). From 3305 blood donors screened, 51 (1.4%) were positive for HIV
      antibodies.

PMID- 18628557
TI  - Predictors of survival in very low birth weight infants at the University
      Hospital of the West Indies, Jamaica.
AB  - The use of prenatal steroids is an effective, simple clinical intervention that
      can be implemented in developing countries to help decrease mortality in very low
      birth weight infants.

PMID- 18628558
TI  - Visceral leishmanisis in paediatrics: a study of 367 cases in southwest Iran.
AB  - Kala-azar (visceral leishmaniasis [VL]) is endemic in southern Iran. We
      retrospectively evaluated 367 infants and children suffering from VL at hospitals
      affiliated to the Shiraz University of Medical Sciences in Fars Province,
      southwest Iran). Seasonal variations were observed with more cases presenting in
      late winter, spring and fewer in summer. The predominant clinical features in
      these patients were chronic fever, pallor, weight loss, abdominal distention and
      hepatosplenomegaly. Lymphadenopathy was less common. Common laboratory
      abnormalities included anaemia, leukopenia, thrombocytopenia, hypoalbuminaemia
      and hypergammaglobulinaemia. Liver function tests were deranged in two-thirds of
      the patients. The immunofluorescence antibody test was positive in all patients
      and all of them had a positive bone marrow smear or a culture for Leishmania
      donovani. Patients responded well to glucantim therapy with a cure rate of 96.7%.
      Relapse was observed in 8.2% (30). Mortality in this series was 7.3%. Twenty
      patients died during their therapy period. Jaundice and grossly deranged liver
      function tests were found to be bad prognostic signs.

PMID- 18628559
TI  - Accidental childhood fatalities in Manipal, India.
AB  - Children in the first decade of life are extremely vulnerable to accidents.
      Seventy-five cases of accidental deaths in children aged less than ten years were
      identified in a retrospective review of medicolegal autopsies during 1993-2006 in
      Manipal, India. Boys were more likely to suffer accidental death that girls (male
      female ratio 2.3:1). Road traffic accidents accounted for the majority of the
      deaths (56%), followed by burns (21.4%).

PMID- 18628560
TI  - Caesarean myomectomy in Aba, southeastern Nigeria.

PMID- 18628561
TI  - Bullous erythema multiforme after treatment with Malarone, a combination
      antimalarial composed of atovaquone and proguanil hydrochloride.
AB  - We report on a Kenyan woman who developed bullous erythema multiforme, in
      association with Malarone treatment.

PMID- 18628562
TI  - Clinical analysis of 52 cases of neurocysticercosis.
AB  - We studied 52 cases of neurocysticercosis from January 1991 to December 2006 in
      order to increase our understanding of the diagnosis and treatment of the
      disease. The majority of patients were between 18 and 45 years old (78.8%). Men
      were more subject to the disease than women. The urban population was more at
      risk than the rural population. The treatment involved the use of mannitol,
      dexamethasone and oral administrations of albendazole or praziquantel. The
      effectiveness rate was 57.7% (30), the improvement rate was 28.8% (15), and the
      inefficacy rate was 14.0% (6). Neurocysticercosis was easy to misdiagnose.
      Praziquantel and albendazole are effective drugs for neurocysticercosis.

PMID- 18628563
TI  - Prolactin and alternative medicines: a word of caution.

PMID- 18628564
TI  - From home delay to institutional neglect: an emerging trend in obstructed labour.
AB  - Analysis of 146 patients managed for obstructed labour at a referral tertiary
      hospital in South West Nigeria shows that labour became obstructed in a lower
      cadre health facility among majority (76.7%) of the women. This calls for
      improved maternity service delivery in our locality.

PMID- 18628565
TI  - Timing is everything: age of onset influences long-term retinopathy risk in type
      2 diabetes, independent of traditional risk factors.
AB  - OBJECTIVE: To test the hypothesis that age of type 2 diabetes onset influences
      inherent susceptibility to diabetic retinopathy, independent of disease duration
      and degree of hyperglycemia. RESEARCH DESIGN AND METHODS: Retinopathy data from
      624 patients with a type 2 diabetes duration of 20-30 years (group A) were
      analyzed by stratifying patients according to age of onset of diabetes and
      glycemic control. Retinopathy status was scored clinically as per a modified
      Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. To obviate
      possible bias due to a higher attrition from comorbidities in those with later
      onset diabetes and retinopathy, 852 patients with type 2 diabetes of shorter
      duration (10-12 years, group B) were similarly studied. RESULTS: Prevalence and
      severity of retinopathy was significantly higher in the younger-onset, group A
      patients. When further stratified according to mean A1C, retinopathy risk
      remained increased in younger-onset patients. The greatest impact was seen in
      those with a mean A1C >9% (odds ratio [OR] for retinopathy 16.6, 7.5, and 2.7 for
      age of diagnosis <45, 45-55, and >55 years, respectively, P = 0.003). By logistic
      regression, earlier type 2 diabetes onset is associated with increased
      retinopathy risk, independent of traditional risk factors (OR of retinopathy 1.9,
      1.1, and 1 for age of onset <45, 45-55, and >55 years, respectively). Similar
      results were found in group B patients. CONCLUSIONS: These data suggest an
      increased inherent susceptibility to diabetic retinopathy with earlier-onset type
      2 diabetes. This further supports the importance of delaying development of
      diabetes and also implies a need for more stringent metabolic targets for younger
      individuals.

PMID- 18628566
TI  - Changes in risk variables of metabolic syndrome since childhood in pre-diabetic
      and type 2 diabetic subjects: the Bogalusa Heart Study.
AB  - OBJECTIVE: That type 2 diabetes is associated with the metabolic syndrome is
      known. However, information is lacking regarding the long-term and adverse
      changes of metabolic syndrome variables in the development of type 2 diabetes
      from childhood to adulthood. RESEARCH DESIGN AND METHODS: Observations were
      examined, retrospectively, in a community-based cohort of normoglycemic (n =
      1,838), pre-diabetic (n = 90), and type 2 diabetic (n = 60) subjects followed
      serially for cardiovascular risk factors during childhood (4-11 years),
      adolescence (12-18 years), and adulthood (19-44 years). RESULTS: Diabetic
      subjects versus normoglycemic subjects had significantly higher levels of
      subscapular skinfold, BMI, triglycerides, glucose, insulin, and homeostasis model
      assessment of insulin resistance and lower levels of HDL cholesterol beginning in
      childhood and higher levels of mean arterial pressure (MAP) in adolescence and
      adulthood. In a multivariate model including BMI, MAP, HDL cholesterol, LDL
      cholesterol, triglycerides, glucose, and insulin, adjusted for age, age(2), race,
      sex, and race x sex interaction, adverse changes in glucose and LDL cholesterol
      were independently associated with pre-diabetic subjects, whereas adverse changes
      in BMI, glucose, and HDL cholesterol were associated with diabetic subjects. As
      young adults, pre-diabetic and diabetic groups displayed a significantly higher
      prevalence of obesity, hypertension, dyslipidemia, hyperinsulinemia, and
      metabolic syndrome. CONCLUSIONS: These findings indicate that adverse levels of
      risk variables of metabolic syndrome, adiposity, and measures of glucose
      homeostasis accelerating since childhood characterize the early natural history
      of type 2 diabetes and underscore the importance of early prevention and
      intervention on risk factors beginning in childhood.

PMID- 18628567
TI  - Alcohol consumption, mediating biomarkers, and risk of type 2 diabetes among
      middle-aged women.
AB  - OBJECTIVE: The purpose of this study was to investigate whether adiponectin
      concentrations and biomarkers of inflammation, endothelial dysfunction, and
      insulin resistance mediate the association between alcohol consumption and
      diabetes. RESEARCH DESIGN AND METHODS: In a nested case-control study of 705
      women with incident diabetes and 787 matched control subjects, we examined the
      adjusted relationship between baseline alcohol consumption and risk of diabetes
      before and after adjustment for markers of inflammation/endothelial dysfunction
      (C-reactive protein, vascular cell adhesion molecule-1, intercellular adhesion
      molecule-1, E-selectin, tumor necrosis factor-alpha receptor 2, and interleukin
      6), fasting insulin, and adiponectin concentrations. RESULTS: Alcohol consumption
      was associated with a decreased risk of diabetes (odds ratio per 12.5 g/day
      increment in alcohol use 0.58; 95% CI 0.49-0.69; P < 0.001). Adjustment for BMI
      attenuated the association by 25%. None of the markers of inflammation or fasting
      insulin appeared to account for >2% of the observed relationship. Without
      adjustment for BMI, these biomarkers individually explained slightly more of the
      association, but <10% in all cases. Adiponectin accounted for 25% in a fully
      adjusted model and for 29% without adjustment for BMI. CONCLUSIONS: In this
      population of women, alcohol consumption was inversely associated with risk of
      type 2 diabetes. Adiponectin appeared to be a mediator of this association, but
      circulating biomarkers of inflammation, endothelial dysfunction, and fasting
      insulin did not explain this association. These results suggest that further
      research is needed into the potentially mediating roles of other biomarkers
      affected by alcohol consumption.

PMID- 18628568
TI  - Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC
      cohort and their relationship with nephropathy and macrovascular complications.
AB  - OBJECTIVE: Because endothelial cell dysfunction and inflammation are key
      contributors to the development of complications in type 1 diabetes, we studied
      risk factors related to endothelial dysfunction and inflammation (C-reactive
      protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular
      adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of
      patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of
      Diabetes Intervention and Complications (EDIC) study cohort. RESEARCH DESIGN AND
      METHODS: We determined which of these risk factors or clusters thereof are
      associated with the presence of and subsequent development of nephropathy and
      macrovascular complications (reflected by carotid intima-media thickness [IMT]).
      RESULTS: After adjustment for conventional risk factors (age, sex, DCCT treatment
      group, diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, total
      and HDL cholesterol, and smoking status), fibrinogen remained strongly associated
      with progression of internal and common carotid IMT (P < 0.01) and soluble E
      selectin had a strong association with nephropathy (P < 0.01). CONCLUSIONS: The
      best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen,
      and the levels of soluble E-selectin discriminate patients with albuminuria
      better than conventional risk factors.

PMID- 18628569
TI  - Effect of aging on A1C levels in individuals without diabetes: evidence from the
      Framingham Offspring Study and the National Health and Nutrition Examination
      Survey 2001-2004.
AB  - OBJECTIVE: Although glycemic levels are known to rise with normal aging, the
      nondiabetic A1C range is not age specific. We examined whether A1C was associated
      with age in nondiabetic subjects and in subjects with normal glucose tolerance
      (NGT) in two population-based cohorts. RESEARCH DESIGN AND METHODS: We performed
      cross-sectional analyses of A1C across age categories in 2,473 nondiabetic
      participants of the Framingham Offspring Study (FOS) and in 3,270 nondiabetic
      participants from the National Health and Nutrition Examination Survey (NHANES)
      2001-2004. In FOS, we examined A1C by age in a subset with NGT, i.e., after
      excluding those with impaired fasting glucose (IFG) and/or impaired glucose
      tolerance (IGT). Multivariate analyses were performed, adjusting for sex, BMI,
      fasting glucose, and 2-h postload glucose values. RESULTS: In the FOS and NHANES
      cohorts, A1C levels were positively associated with age in nondiabetic subjects.
      Linear regression revealed 0.014- and 0.010-unit increases in A1C per year in the
      nondiabetic FOS and NHANES populations, respectively. The 97.5th percentiles for
      A1C were 6.0% and 5.6% for nondiabetic individuals aged <40 years in FOS and
      NHANES, respectively, compared with 6.6% and 6.2% for individuals aged >or=70
      years (P(trend) < 0.001). The association of A1C with age was similar when
      restricted to the subset of FOS subjects with NGT and after adjustments for sex,
      BMI, fasting glucose, and 2-h postload glucose values. CONCLUSIONS: A1C levels
      are positively associated with age in nondiabetic populations even after
      exclusion of subjects with IFG and/or IGT. Further studies are needed to
      determine whether age-specific diagnostic and treatment criteria would be
      appropriate.

PMID- 18628570
TI  - Prediction of the onset of disturbed eating behavior in adolescent girls with
      type 1 diabetes.
AB  - OBJECTIVE: The purpose of this study was to identify predictors of the onset of
      disturbed eating behavior (DEB) in adolescent girls with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: In this prospective study, participants completed
      the Children's Eating Disorder Examination interview and self-report measures at
      baseline and at four follow-up assessments over 5 years. Participants were 126
      girls with type 1 diabetes, aged 9-13 years at baseline. Of the 101 girls who did
      not have DEB at baseline, 45 developed DEB during the follow-up period; the 38
      for whom data were available for the assessment before onset of DEB were compared
      with 38 age-matched girls who did not develop DEB. DEB was defined as dieting for
      weight control, binge eating, self-induced vomiting, or the use of diuretics,
      laxatives, insulin omission, or intense exercise for weight control. RESULTS:
      Logistic regression indicated that a model including BMI percentile, weight and
      shape concern, global and physical appearance-based self-worth, and depression
      was significantly associated with DEB onset (chi(2) = 46.0, 5 d.f., P < 0.0001)
      and accounted for 48.2% of the variance. CONCLUSIONS: Even though scores on the
      measures were within the published normal range, the onset of DEB was predicted
      by higher depression and weight and shape concerns and lower global and physical
      appearance-based self-worth as well as higher BMI percentile 1-2 years earlier
      compared with those not developing DEB. Early interventions focused on helping
      girls with diabetes develop positive feelings about themselves, their weight and
      shape, and their physical appearance may have protective value.

PMID- 18628571
TI  - Diabetes and obesity-related risks for pelvic reconstructive surgery in a cohort
      of Swedish twins.
AB  - OBJECTIVE: To determine the diabetes- and obesity-related risks for surgically
      managed stress urinary incontinence and pelvic organ prolapse. RESEARCH DESIGN
      AND METHODS: This twin cohort study used the Swedish Twin Register to identify
      8,443 female twin pairs born from 1926 through 1958. The association between
      diabetes and pelvic floor surgery was estimated while taking into account the
      correlated (twin) structure of the data. RESULTS: For type 1 and type 2 diabetes,
      no significant associations were observed for stress urinary incontinence (odds
      ratio [OR] 1.0 [95% CI 0.1-9.2] and 2.0 [1.0-4.0], respectively). There were no
      cases of prolapse surgery in type 1 diabetic subjects, and for type 2 diabetes
      the risk estimate was nonsignificant (1.6 [1.0-2.7]). BMI >25 kg/m(2), age >or=60
      years, and childbirth were the strongest risk factors for having incontinence
      surgery. CONCLUSIONS: Our data suggest that diabetes is not associated with
      stress urinary incontinence or pelvic organ prolapse surgery.

PMID- 18628572
TI  - Glucose intolerance in pregnancy and future risk of pre-diabetes or diabetes.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that any degree
      of abnormal glucose homeostasis detected on antepartum screening for gestational
      diabetes mellitus (GDM) should be associated with an increased risk of postpartum
      pre-diabetes or diabetes. RESEARCH DESIGN AND METHODS: In this prospective cohort
      study, 487 women underwent 1) antepartum GDM screening by a glucose challenge
      test (GCT) and a diagnostic oral glucose tolerance test (OGTT) and 2) postpartum
      metabolic characterization by OGTT at 3 months after delivery. Four baseline
      glucose tolerance groups were defined on the basis of the antepartum GCT/OGTT: 1)
      GDM (n = 137); 2) gestational impaired glucose tolerance (GIGT) (n = 91); 3)
      abnormal GCT with normal glucose tolerance on an OGTT (abnormal GCT NGT) (n =
      166); and 4) normal GCT with NGT on an OGTT (normal GCT NGT) (n = 93). RESULTS:
      The prevalence of postpartum glucose intolerance (pre-diabetes or diabetes)
      increased across the groups from normal GCT NGT (3.2%) to abnormal GCT NGT
      (10.2%) to GIGT (16.5%) to GDM (32.8%) (P(trend) < 0.0001). On logistic
      regression analysis, all three categories of abnormal glucose homeostasis in
      pregnancy independently predicted postpartum glucose intolerance: abnormal GCT
      NGT odds ratio (OR) 3.6 (95% CI 1.01-12.9); GIGT OR 5.7 (1.6-21.1); and GDM OR
      14.3 (4.2-49.1). Furthermore, both in pregnancy and at 3 months postpartum,
      insulin sensitivity (IS(OGTT)) and pancreatic beta-cell function (insulinogenic
      index/homeostasis model assessment of insulin resistance) progressively decreased
      across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all
      P(trend) < 0.0001). CONCLUSIONS: Any degree of abnormal glucose homeostasis in
      pregnancy independently predicts an increased risk of glucose intolerance
      postpartum.

PMID- 18628573
TI  - Superior mesenteric artery syndrome in type 1 diabetes masquerading as
      gastroparesis.
AB  - OBJECTIVE: To describe and discuss a case of superior mesenteric artery syndrome
      (SMAS) presenting with gastrointestinal signs and symptoms mistakenly attributed
      to, and treated as, diabetic gastroparesis. RESEARCH DESIGN AND METHODS: A case
      report was compiled describing the clinical presentation, including history and
      physical examination, evaluation, diagnosis, and treatment of a patient with type
      1 diabetes presenting with gastrointestinal complications. RESULTS: Clinical
      suspicion combined with the appropriate radiological evaluation led to a
      diagnosis of SMAS, with classic findings of reduced aortomesenteric angle and
      distance. Surgical intervention resulted in resolution of symptoms and recovery
      of glycemic control. CONCLUSIONS: The possibility of SMAS should be considered in
      patients with type 1 diabetes presenting with gastrointestinal symptomatology,
      especially when associated with weight loss.

PMID- 18628574
TI  - Mixed-meal tolerance test versus glucagon stimulation test for the assessment of
      beta-cell function in therapeutic trials in type 1 diabetes.
AB  - OBJECTIVE: Beta-cell function in type 1 diabetes clinical trials is commonly
      measured by C-peptide response to a secretagogue in either a mixed-meal tolerance
      test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet
      Research Group and the European C-peptide Trial (ECPT) Study Group conducted
      parallel randomized studies to compare the sensitivity, reproducibility, and
      tolerability of these procedures. RESEARCH DESIGN AND METHODS: In randomized
      sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST
      tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each)
      with either two MMTTs or two GSTs. RESULTS: Among individuals with up to 4 years'
      duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The
      MMTT stimulus produced significantly higher concentrations of C-peptide than the
      GST. Whereas both tests were highly reproducible, the MMTT was significantly more
      so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects
      preferred the MMTT, and there were few adverse events. Some older subjects
      preferred the shorter duration of the GST. Nausea was reported in the majority of
      GST studies, particularly in the young age-group. CONCLUSIONS: The MMTT is
      preferred for the assessment of beta-cell function in therapeutic trials in type
      1 diabetes.

PMID- 18628575
TI  - Epigenetic control in pituitary tumors.
AB  - Epigenetically-mediated gene dysregulation is a common feature associated with
      human pituitary tumorigenesis. The mechanisms leading to these changes, however,
      remain largely unknown. In this review, we examine changes responsible for DNA
      and histone modifications as independent, butpotentially interrlated modes of
      communication effecting chromatin remodeling. The dynamic properties of the
      enzymes involved in these reactions is highlighted. We use the fibroblast growth
      factor receptor 2 (FGFR2) as a model through which the p53-regulating melanoma
      associated antigen (MAGE) system is governing in pituitary cells. The
      pathogenetic and potential therapeutic implications are discussed.

PMID- 18628576
TI  - Lamivudine treatment improves the prognosis of fulminant hepatitis B.
AB  - OBJECTIVE: The efficacy of lamivudine for fulminant hepatitis B has been reported
      in Europe and West Asia. However, in these reports, the main infection genotype
      is D. Furthermore, if lamivudine improves survival, prognostic factors for
      fulminant hepatitis B may differ from those reported previously. The aim of this
      study was to clarify the prognostic factors and the efficacy of lamivudine for
      fulminant hepatitis B in Japan, where the main infection genotype is B. METHODS:
      This study was a retrospective cohort study. We selected 37 consecutive patients
      with fulminant hepatitis due to acute hepatitis B virus infection. As 4 of them
      had received liver transplantation, the data of 33 patients with a median age of
      45 (range, 20-74) years were analyzed. RESULTS: Lamivudine was administered to 10
      patients. There were no differences in clinical features at the time of the
      diagnosis of fulminant hepatitis B between patients treated with and without
      lamivudine. Survival rates of patients treated with and without lamivudine were
      70% and 26%, respectively. Age (> or =45 years), systemic inflammatory response
      syndrome, and non-administration of lamivudine were associated with fatal
      outcomes. The survival rates of patients treated with and without lamivudine, who
      were in a state of systemic inflammatory response syndrome, were 50% and 9%, and
      in patients aged > or =45 years, 50% and 8%, respectively. CONCLUSION: This study
      suggests the efficacy of lamivudine for fulminant hepatitis B in the area where
      the main infection genotype is B. We consider that lamivudine is worth
      administering to patients with fulminant hepatitis B.

PMID- 18628577
TI  - Suitable treatment period in patients with virological response during
      combination therapy of peginterferon and ribavirin for chronic hepatitis C.
AB  - OBJECTIVE: The aim of this study was to determine the suitable treatment period
      in patients who achieve virological response during combination therapy of
      peginterferon and ribavirin for chronic hepatitis C virus infection. METHODS:
      Inclusion criteria were HCV-genotype 1b, serum HCV RNA level of > or =100 KIU/ml
      before treatment, and negativity of serum HCV RNA during treatment. The 366
      patients were enrolled in this retrospective cohort study. Patients were
      classified into four groups according to difference of response: rapid
      virological response (RVR) at week 4 after the initiation of treatment (n=37),
      early-virological response (EVR) at week 5-12 (n=161), late-virological response
      (LVR) at week 13-24 (n=131), and superlate-virological response (SLVR) at week 25
      48 (n=37). A non-relapse in patients with undetectable HCV RNA during therapy was
      defined as clearance of HCV RNA 6 month after the cessation of therapy. RESULTS:
      Of the 366 patients, 241 had non-relapse and the non-relapse rate in each group
      was 89% (33/37) in RVR, 79% (127/161) in EVR, 54% (71/131) in LVR, and 27%
      (10/37) in SLVR. In RVR, 26 of 27 patients with continuance of negative HCV RNA
      of > or =30 weeks during treatment had non-relapse. In EVR, patients with period
      of negative HCV RNA of > or =40 weeks had non-relapse rate of 90% (71/79). In LVR
      and SLVR, all nine patients with continuance of negative HCV RNA of > or =60
      weeks had non-relapse. CONCLUSION: A suitable treatment period of combination
      therapy for chronic hepatitis C should be determined based on the time of
      attainment of negative HCV RNA.

PMID- 18628578
TI  - Increased serum chitotriosidase activity following restoration of euthyroidism in
      patients with subclinical hypothyroidism.
AB  - OBJECTIVE: Whether to treat subclinical hypothyroidism (SH) remains
      controversial. Serum chitotriosidase activity, a marker of activated macrophages,
      predicts new cardiovascular events. Chitotriosidase activity (ChT) is a new
      cardiovascular risk marker and is independent of C-reactive protein. The purpose
      of this study was to determine ChT levels in SH and to examine the effect of
      levothyroxine replacement on ChT. SUBJECTS AND METHODS: A cohort of 60 patients
      with subclinical hypothyroidism and 62 healthy controls were enrolled in this
      study. Serum total and LDL cholesterol, total homocysteine (t-Hyc), highly
      sensitive C-reactive protein (hsCRP) levels and serum ChT in patients with
      subclinical hypothyroidism at baseline and after achieving euthyroid state by
      levothyroxine were assessed. RESULTS: Pretreatment levels of TSH (10.06+/-5.09
      vs. 2.08+/-0.95 mIU/L, p<0.05), and free T4 (0.94+/-0.21 vs. 1.35+/-0.26 ng/dl,
      p<0.05) were significantly higher than controls while total cholesterol, LDL
      cholesterol, t-Hyc, ChT and hsCRP levels were not different. ChT levels
      significantly increased after replacement therapy (137.2+/-14.18 vs. 156.88+/
      13.10 nmol/mL/h, p<0.05). T-Hyc and hsCRP levels were not significantly different
      after treatment with levothyroxine therapy even in this subgroup of patients.
      None of the other biochemical risk factors improved after euthyroidism in
      patients with SH with average dose of 85+/-30 mug/day when compared to
      pretreatment levels. CONCLUSION: We conclude that clinical management of
      subclinical hypothyroidism does not decrease the serum hsCRP or t-Hyc levels but
      does increase the serum ChT levels. The clinical significance of this increment
      should be studied in further studies.

PMID- 18628579
TI  - The clinically significant estimated glomerular filtration rate for hyperkalemia.
AB  - OBJECTIVE: Reduced glomerular filtration rate (GFR) is a risk factor of
      cardiovascular diseases. Accurate assessment of GFR together with early and
      appropriate treatment of chronic kidney disease (CKD) is important. Although the
      Japanese Society of Nephrology has recently announced two equations (equation
      0.741 and equation 194) to estimate GFR for Japanese, the clinically significant
      estimated GFR (eGFR) in Japanese has not been identified. We examined the
      clinical significance of eGFR with regard hyperkalemia. METHODS: A total of 9,196
      patients who were examined and treated at the Toranomon Hospital between January
      and October 2005 were studied. Patients with a serum potassium level of 5 mEq/L
      or above or who were taking potassium adsorbent were classified as hyperkalemic.
      The effect of eGFR on the incidence of hyperkalemia was examined. The factors
      causing elevated serum potassium were analyzed after excluding the patients on
      potassium absorbent. RESULTS: Multivariate analysis identified reduced eGFR,
      diabetes, male gender, aging, and use of renin-angiotensin system inhibitors as
      the factors associated with an elevated serum potassium level. In an eGFR
      stratified analysis, each subgroup with eGFR below 50 mL/min/1.73 m2when equation
      0.741 was used, and eGFR below 60 mL/min/1.73 m2 when equation 194 was used had a
      significantly higher incidence of hyperkalemia compared with almost all of the
      subgroups with higher eGFR. CONCLUSION: From the viewpoint of the increase in
      incidence of hyperkalemia, using an eGFR below 50 mL/min/1.73 m2 as the cutoff
      has clinical significance when equation 0.741 is used and a cutoff at 60
      mL/min/1.73 m2 is appropriate when equation 194 is used.

PMID- 18628580
TI  - Clinical needs of patients attending a women's health center in Japan.
AB  - BACKGROUND: Many women's health centers (WHC) in Japan use female obstetrician
      gynecologists, not trained in primary care medicine, as providers. It is not
      known whether the clinical needs of patients at WHC are met by these providers.
      OBJECTIVE: To identify the clinical needs of patients attending a WHC in Japan by
      examining their presenting problems and diagnoses. METHODS: We performed a case
      series study of 53 patients at a WHC in a public medical center in Chiba
      Prefecture, Japan. Charts were reviewed for the presenting problems and
      diagnoses. RESULTS: The most common presenting complaints were related to the
      female genital system or the breast (42%) and psychological problems (13%). At
      discharge, the most common diagnoses were psychological (42%). The next most
      common diagnoses were related to the female genital system or the breast (36%).
      The remainder (22%) were related to a variety of organ systems. CONCLUSION:
      Patients at the WHC presented with not only gynecological but also general
      medical and psychological problems and had discharge diagnoses involving a
      variety of organ systems. Physicians at WHCs should be trained in primary care
      medicine to meet the clinical needs of patients.

PMID- 18628581
TI  - The influence of medical jargon mixed with foreign terminology in the Japanese
      clinical environment.
AB  - OBJECTIVES: To identify patient reports about their difficulties with medical
      jargon, to classify the most problematic types, and to examine the socio
      demographic factors associated with them. METHODS: A cross-sectional nationwide
      survey (October 6 and November 4, 2004) was conducted. Out of 4,500 Japanese
      people (aged 15 years and older) who had seen physicians, 3,090 agreed to
      participate (response rate: 69%). Participants were asked the following: "Do you
      find physicians that use medical jargon difficult to understand?" and "What type
      of words did your physician use that required further explanation or
      clarification?" RESULTS: Of 3,090 respondents, 1,117 participants (36.1%; 95%
      confidence interval, 34.5-37.8%) reported difficulties understanding medical
      jargon. Those between the ages of 30 and 49 years, self-employed workers,
      homemakers, and unemployed individuals experienced the most difficulties.
      Difficult jargon included: 1) technical Japanese words, such as Kakutan Saibo
      shin (sputum cytology) (57% of participants); 2) English medical terminology,
      such as clinical path (57%); and 3) English medical abbreviations, such as EBM
      (47%). CONCLUSIONS: In addition to avoiding technical words when communicating
      with their patients, Japanese physicians should consider the unique medical
      situation in which foreign terminology and abbreviations are used in Japan.
      Translation of foreign terminology into Japanese can be helpful for patients.
      Physicians should take the initiative to educate patients and familiarize them
      with foreign terminology and abbreviations.

PMID- 18628582
TI  - Solid-pseudopapillary tumor of the pancreas showing a remarkable reduction in
      size over the 10-year follow-up period.
AB  - An 18-year-old healthy woman was admitted to our department for further
      evaluation of a pancreatic mass (45 mm in diameter) by transabdominal ultrasound
      at a general health check. Solid-pseudopapillary tumor (SPT) was suspected from
      the findings of diagnostic images. Therefore, surgery was recommended. The
      patient and her family, however, refused surgery. Ultrasound-guided
      transcutaneous biopsy revealed proliferation of tumor cells with small nuclei
      showing a pseudopapillary arrangement. PAS positive granules and alpha-1
      antitrypsin positive cells were proven, which led to the diagnosis of SPT. As the
      grade of atypism of the tumor cells was low, the patient underwent follow-up
      examination once a year at our outpatient department thereafter. The tumor
      gradually decreased its maximum diameter in 10 years from 45 mm to 15 mm. Thus
      far, there have been very few reports on the natural course of SPT, and this is
      the first report describing marked spontaneous shrinkage of a tumor in a long
      follow-up period.

PMID- 18628583
TI  - Acute cytomegalovirus infection superimposed on corticosteroid-naive ulcerative
      colitis.
AB  - Most cases of cytomegalovirus (CMV) colitis that develop in patients with
      inflammatory bowel disease (IBD) are caused by a reactivation of a latent virus;
      acute CMV infections are rare. Treatment with immunosuppressive agents further
      increases the infection risk. Here, we present a 32-year-old man with acute CMV
      mononucleosis and colitis, superimposed on corticosteroid-naive ulcerative
      colitis (UC). The diagnosis was confirmed by a viral-like prodrome, positive CMV
      antigenemia (C7-HRP), a positive CMV IgM titer, the presence of atypical
      lymphocytes, mild transaminase elevation, and immunohistological detection of CMV
      positive cells in his colonic mucosa. Gancyclovir was intravenously administered,
      and all symptoms were improved.

PMID- 18628584
TI  - Pseudoaldosteronism caused by combined administration of cilostazol and
      glycyrrhizin.
AB  - We report a case of obvious pseudoaldosteronism which occurred after the
      additional administration of cilostazol against arteriosclerosis obliterans (ASO)
      for bilateral legs in a 65 year-old man patient who had safely received
      glycyrrhizin for the previous ten years. Serum potassium level of the patient had
      been kept above 4 mEq/L until initiating cilostazol in November, 2006, then
      gradually decreased to 2.5 mEq/L for the following seven months. Both plasma
      renin activity and aldosterone were suppressed under co-administration of the
      angiotensin converting enzyme inhibitor, imidapril and the angiotensin II
      receptor blocker, olmesartan, both of which had been prescribed for longer than a
      year. Urinary potassium excretion was accelerated even in the critical level of
      hypokalemia. Because other drugs and supplements had not been changed at least
      for a year, pseudoaldosteronism caused by the combination of glycyrrhizin and
      another triggering factor, possibly cilostazol was highly suspected. By
      discontinuation of glycyrrhizin, potassium supplement, and the additional
      administration of the aldosterone blocker, spironolactone, the serum potassium
      level returned to the normal level two weeks later, even though cilostazol had
      been continued to avoid progression in his ASO. This is the first report of a
      case exhibiting pseudoaldosteronism induced by the interaction of glycyrrhizin
      with cilostazol, not by glycyrrhizin alone.

PMID- 18628585
TI  - Probable cerebral Mycobacterium avium complex-related immune reconstitution
      inflammatory syndrome in an HIV-infected patient.
AB  - The advent of highly active anti-retroviral therapy (HAART) has reduced both the
      morbidity and incidence of acquired immunodeficiency syndrome (AIDS)-related
      central nervous system (CNS) diseases. However, some patients seem to suffer
      paradoxical clinical deterioration after starting HAART, known as immune
      reconstitution inflammatory syndrome (IRIS). We report a rare case of probable
      Mycobacterium avium complex (MAC) infection of the brain in a patient with AIDS
      who had been treated effectively for probable pulmonary and cerebral MAC
      infection, with both lesions recurring after significant decreases in plasma
      human immunodeficiency virus type-1 viral load following initiation of HAART.
      This case appears to represent the first precise clinicopathological description
      of severe ventriculo-encephalitis in CNS MAC-related IRIS.

PMID- 18628586
TI  - Facial muscular atrophy in a myasthenia gravis patient.
AB  - A 56-year-old man with anti-acetylcholine receptor antibody-mediated myasthenia
      gravis had bilateral facial muscular atrophy and had noticed blepharoptosis 15
      years earlier. From 45 to 51 years of age, 5-10 mg prednisolone and 180 mg
      pyridostigmine daily relieved his symptoms. Subsequently, these treatments no
      longer improved the facial weakness, though blepharoptosis was absent. At 56
      years of age, the edrophonium test and repetitive supramaximal stimulation
      testing of the orbicularis oris were negative. Frontalis muscle needle
      electromyography showed low amplitude polyphasic units and an incomplete
      interference pattern. Facial muscle atrophy, caused by disuse atrophy from
      neuromuscular junction depletion, contributed to this patient's facial weakness.

PMID- 18628587
TI  - Diphyllobothriasis nihonkaiense: possibly acquired in Switzerland from imported
      Pacific salmon.
AB  - A 5-year-old Japanese boy passed tapeworm strobila while he was living in
      Switzerland. During a short visit to Japan, he was successfully treated with a
      single dose of praziquantel. DNA sequences of ITS1, cox1 and nd3 genes from the
      tapeworm were compatible with those of Diphyllobothrium nihonkaiense rather than
      Diphyllobothrium latum, which is prevalent in Europe. The patient consumed
      imported salmon in Switzerland. This case highlights the globalization of D.
      nihonkaiense, which was once restricted to the Far East, and reflects the
      worldwide demand for seafood.

PMID- 18628588
TI  - Combined treatment with oral kanamycin and parenteral antibiotics for a case of
      persistent bacteremia and intestinal carriage with Campylobacter coli.
AB  - Campylobacter coli (C. coli) is a rare pathogen of bacteremia, but in
      immunocompromised hosts, C. coli occasionally causes bacteremia which can be
      refractory to antibiotic treatment. We report a case of C. coli bacteremia in a
      patient with X-linked agammaglobulinemia. Bacteremia relapsed repeatedly in spite
      of treatment with combined intravenous antibiotics. C. coli was observed in the
      biopsy specimens from the intestinal mucosa, suggesting intestinal carriage and
      reservoir of recurring infection. The addition of oral kamamycin with intravenous
      antibiotics was successful in eradicating C. coli from the blood and intestine.

PMID- 18628589
TI  - Congenital bronchobiliary fistula in a 65-year-old woman.
AB  - Congenital bronchobiliary fistula (CBBF) is quite a rare malformation and the
      diagnosis is usually made within a few hours or years from birth because of lower
      respiratory diseases beginning from early infancy. Surgical repair is necessary.
      Of the 29 cases reported, 4 occurred in adults aged 22-32 years. We detected CBBF
      incidentally in a 65-year-old woman. During bronchoscopy and thoracic computed
      tomographic study of the pulmonary nodules, we found an accessory bronchus
      descending from the carina and composed of a dark green secretion that contained
      10% bilirubin. Drip infusion cholangiography revealed air in the left bile duct.
      Cholescintigraphy showed dilatation of the left bile duct and radiotracer pooling
      at the top edge of the left hepatic lobe. These findings indicated a narrow
      fistula between the airway and biliary duct. We attributed the patient's long
      survival without major complications to the narrowness of the communication. To
      our best knowledge, this is the fifth and oldest reported adult diagnosed with
      CBBF.

PMID- 18628590
TI  - Expression of nerve growth factor and its receptors trkA and p75 and inhibin
      alpha-subunit in the ovarian interstitial cells of lactating golden hamsters.
AB  - Characteristic daily increases in the plasma levels of luteinizing hormone (LH)
      are present every afternoon during lactation in golden hamsters. The objective of
      this study was to investigate the effect of the diurnal rhythm of increases in LH
      on expression of nerve growth factor (NGF), its receptors trkA and p75 and
      inhibin alpha-subunit in the ovarian interstitial cells of lactating golden
      hamsters. Both lactating and non-lactating groups of postpartum golden hamsters
      were used in this study. The expression of NGF, its receptors trkA and p75 and
      inhibin alpha-subunit were determined by immunohistochemistry. Positive staining
      of NGF, trkA and p75 was found in the interstitial cells of the lactating group,
      and no immunoreactivity for NGF, trkA or p75 was observed in the ovarian
      interstitial cells of the non-lactating group. In addition, immunostaining of
      inhibin alpha-subunit was also observed in the interstitial cells of the
      lactating group but not in those of the non-lactating group. Immunostaining of
      the inhibin/activin beta(A)- and beta(B)-subunits was observed in the granulosa
      cells of antral follicles, but not in the interstitial cells of the lactating and
      non-lactating animals. These results suggest that the diurnal rhythm increases in
      LH can induce expression of NGF, trkA, p75 and inhibin alpha-subunit in the
      ovarian interstitial cells of lactating golden hamsters and that NGF, its
      receptors trkA and p75 and inhibin alpha-subunit may have the capacity for
      autocrine or paracrine modulation of interstitial cell differentiation in golden
      hamsters.

PMID- 18628591
TI  - Isolation and culture of rabbit primordial germ cells.
AB  - Primordial germ cells (PGCs) are embryonic precursors of the gametes of adult
      animals and are considered stem cells of the germline. Since their proliferation
      in vitro correlates well with the schedule of developmental changes in vivo, they
      might be interesting research tools for genomic imprinting, germ-cell tumors and
      fertility. Furthermore, once primordial germ cells are separated and placed on a
      feeder layer with cytokines, they become cultured pluripotent cell lines called
      embryonic germ (EG) cells. EG cells share several important characteristics with
      embryonic stem (ES) cells as they can also contribute to the germ line of
      chimeras. To investigate the characteristics of PGCs and establish rabbit EG
      (rEG) cells, we cultured rabbit PGCs (rPGCs) in vitro with various combinations
      of leukemia inhibitory factor (LIF), basic fibroblast growth factor (bFGF) and
      forskolin on inactivated mouse embryonic fibroblast (MEF) feeder layers. The
      present study found PGC proliferation in early cultures and induction of rEG-like
      colonies. These cells expressed pluripotent markers, such as alkaline phosphatase
      activity, OCT-4, Sox-2 and SSEA-1, in the undifferentiated state; however, the
      cells did not develop into a teratoma when injected into the kidney capsules of
      SCID mice, although the restricted differentiation potentials to neural cells
      were determined via embryoid body formation. From these characteristics and
      further characterization of the germ stem cell markers Vasa, SCP-1 and SCP-3, we
      suggested that these were hybrid cells with characteristics somewhere between PGC
      and EG cells.

PMID- 18628593
TI  - Molecular cloning and phylogenetic analysis of inflammatory cytokines of the
      ferret (Mustela putorius furo).
AB  - The present study determined the cDNA and deduced amino acid sequences of ferret
      (Mustela putorius furo) inflammatory cytokines, interferon (IFN)-gamma,
      interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha. The
      homologies of the nucleotide sequences of IFN-gamma, IL-1beta, IL-6, IL-8 and TNF
      alpha of the ferret to those from other mammalian species ranged from 64.3-92.9%,
      73.0-83.9, 58.1-84.8%, 58.1-89.7% and 79.0-95.0%, respectively. As distinctive
      amino acid residues constituting various motifs and ligand-binding sites and
      cysteine residues were highly conserved in ferret inflammatory cytokine proteins,
      ferret cytokines may have fundamentally similar functions to those of other
      mammals. Phylogenetic analyses based on the deduced amino acid sequences revealed
      that all ferret inflammatory cytokines were more closely related to those of the
      Carnivora order, specifically dog and cat, than to other species.

PMID- 18628592
TI  - Mitochondrial transmembrane potential and reactive oxygen species generation
      regulate the enhanced effect of CCCP on TRAIL-induced SNU-638 cell apoptosis.
AB  - TRAIL is a member of the tumor necrosis factor family and engages apoptosis via
      recruitment and rapid activation of caspase-8. This study investigated the effect
      of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a classic uncoupler of
      oxidative phosphorylation, on TRAIL-induced apoptosis in SNU-638 cells derived
      from human gastric cancer cells. It was found that treatment with CCCP followed
      by incubation with TRAIL markedly enhanced apoptosis by 2 fold compared with
      treatment with TRAIL alone. This effect was accompanied by reduction in
      mitochondrial transmembrane potential and generation of reactive oxygen species.
      This sensitization was inhibited by N-acetyl-l-cysteine, which restored the
      mitochondrial transmembrane potential and reduced reactive oxygen species
      generation. Treatment with N-acetyl-L-cysteine also inhibited expression of
      apoptotic proteins such as Bax and Smac and abrogated caspase-8 activation.
      Moreover, treatment with N-acetyl-L-cysteine prior to induction with TRAIL
      increased expression of the anti-apoptotic Bcl-2 protein. These data indicate
      that CCCP enhanced TRAIL-induced apoptosis by dissipation of mitochondrial
      transmembrane potential and reactive oxygen species, suggesting that treatment
      with CCCP combined with that with TRAIL can be an efficient method to induce
      death of tumor cells, particularly cells that are resistant to TRAIL-induced
      apoptosis.

PMID- 18628594
TI  - Effect of 6-mercaptopurine on rat placenta.
AB  - In order to investigate the toxic effects of 6-mercaptopurine (6-MP) on placental
      development, we examined sequential morphology in the placentas from rats exposed
      to 6-MP. 6-MP was intraperitoneally administered at 60 mg/kg during gestation
      days (GDs) 11 to 12, and the placentas were sampled on GD 13, 15 or 21. In the 6
      MP-treated group, maternal body weight suppression, increased death embryo/fetus
      ratio and some malformations were observed. The placenta weights were decreased
      on GDs 15 and 21. Macroscopically, placentas on GD 21 were small, brittle and
      thin with a white peripheral rim. Histopathologically, in the labyrinth zone, 6
      MP treatment mainly evoked decreased mitosis on GDs 13 and 15, increased
      apoptotic cell on GDs 13, 15 and 21 and thinning on GDs 15 and 21. In the basal
      zone, 6-MP evoked decreased mitosis on GDs 13, and PAS-positive material in the
      spongiotrophoblasts was still detected on GD 15. Thickening of the basal zone was
      observed with cytolysis of glycogen cells, apoptosis and an increased number of
      composed cells on GD 21. In conclusion, 6-MP administration in pregnant rats
      induced growth arrest of the labyrinth zone and developmental delay in the basal
      zone, leading to small placentas. The fetotoxicity of 6-MP may be responsible for
      its direct anti-proliferative effects and resulting placental dysfunction.

PMID- 18628596
TI  - Etiologic study of upper respiratory infections of household dogs.
AB  - Infectious tracheobronchitis (ITB), also known as the kennel cough, is a
      respiratory syndrome of dogs and usually appears to be contagious among dogs
      housed in groups. Etiologic agent of ITB is multiple and sometimes complex. In
      the present study, 68 household dogs showing clinical signs of respiratory
      infection were examined, and 20 dogs (29.4%) were found to be positive for either
      of following agents. Bordetella bronchiseptica (B.b.) was most frequently
      detected from nasal and oropharynx sites of 7 dogs (10.3%). Among the viruses
      examined, canine parainfluenza virus (CPIV) was detected with the highest
      frequency (7.4%). Other pathogens included in the order of frequency group 1
      canine coronavirus (4.4%), canine adenovirus type 2 (2.9%), group 2 canine
      respiratory coronavirus (1.5%), and canine distemper virus (1.5%). Only 2 cases
      showed mixed infections. Neither influenza A virus nor canine bocavirus (minute
      virus of canines) was found in any dogs examined. These results indicate that
      both B.b. and CPIV are likely to be the principal etiologic agents of canine ITB
      in Japan, and they may be considered as the target for prophylaxis by
      vaccination.

PMID- 18628595
TI  - Development of a pen-site test kit for the rapid diagnosis of H7 highly
      pathogenic avian influenza.
AB  - As well as H5 highly pathogenic avian influenza viruses (HPAIV), H7 HPAIV strains
      have caused serious damages in poultry industries worldwide. Cases of bird-to
      human transmission of H7 HPAIV have also been reported [11]. On the outbreak of
      avian influenza, rapid diagnosis is critical not only for the control of HPAI but
      also for human health. In the present study, a rapid diagnosis kit based on
      immunochromatography for the detection of H7 hemagglutinin (HA) antigen of
      influenza A virus was developed using 2 monoclonal antibodies that recognize
      different epitopes on the H7 HAs. The kit detected each of the tested 15 H7
      influenza virus strains and did not react with influenza A viruses of the other
      subtypes than H7 or other avian viral and bacterial pathogens. The kit detected
      H7 HA antigen in the swabs and tissue homogenates of the chickens experimentally
      infected with HPAIV strain A/chicken/Netherlands/2586/03 (H7N7). The results
      indicate that the present kit is specific and sensitive enough for the diagnosis
      of HPAI caused by H7 viruses, thus, recommended for the field application as a
      pen-site test kit.

PMID- 18628597
TI  - Genoepidemiological evaluation of Bovine viral diarrhea virus 2 species based on
      secondary structures in the 5' untranslated region.
AB  - Bovine viral diarrhea virus 2 (BVDV-2) strains demonstrated in cattle, sheep, and
      adventitious contaminants of biological products have been evaluated by the
      palindromic nucleotide substitutions (PNS) method at the three variable loci (V1,
      V2 and V3) in the 5' untranslated region (UTR), to determine their taxonomical
      status. Variation in conserved genomic sequences was used as parameter for
      epidemiological evaluation of the species in relation with geographical
      distribution, animal host and virulence. Four genotypes, BVDV-2a, BVDV-2b, BVDV
      2c, and BVDV-2d have been identified within the species. Taxonomical segregation
      corresponded to geographical distribution of genotype variants. Genotype 2a was
      present worldwide, and was the only circulating also in sheep, in addition to
      cattle. Genotypes 2b, 2c and 2d were restricted to South America. Contamination
      of biological products was related to genotypes 2a and 2d. Genetic variation
      could be related with chronological diffusion of the BVDV-2 species variants in
      different geographic areas. Chronologically, the species emerged in North America
      in 1978, spreading in UK and Japan, continental Europe, South America and New
      Zealand. Correlation between clinical features related with isolation of BVDV-2
      strains and genetic variation indicated that subgenotype 1, variant 4 of genotype
      2a was related with hemorrhagic syndrome. These observations suggest that
      evaluation of genomic secondary structure, by identifying markers for expression
      of virus biological activities and species evolutionary history, may be applied
      as useful tool for epidemiological evaluation of the BVDV-2 species, and possibly
      for other species of the genus Pestivirus.

PMID- 18628598
TI  - Phenotypic analysis and effects of sequential administration of activated canine
      lymphocytes on healthy beagles.
AB  - We attempted to accumulate the basic data for evaluation of activated lymphocyte
      therapy for small animal medicine. The peripheral blood mononuclear cells (PBMCs)
      collected from healthy dogs were activated using anti-CD3 antibody and human
      recombinant (hr) interleukin (IL)-2 and reactivated using hr interferon (IFN)
      alpha and hr IL-2. The property of obtained cells was compared with PBMCs. The
      number of cells was shown to have increased approximately>50 -fold by
      cultivation. The proportion of CD8+ cells was significantly increased, the
      cytotoxicity of the cultured cells was revealed to have been reinforced.
      Additionally, CD56 mRNA levels tended to have increased. The cells obtained by
      this method were confirmed to be activated lymphocytes. Furthermore, we
      investigated the effects of sequential administration of the obtained cells to
      healthy dogs. By sequential administration of the activated lymphocytes, the cell
      proliferative activity, proportion of CD4+ cells and CD8+ cells, and serum IFN
      gamma concentration were shown to have increased, and no severe adverse effects
      were observed. Consequently, activated lymphocytes could be induced using anti
      CD3 antibody and IL-2 in healthy dogs, and sequential administration of activated
      lymphocytes reinforced the recipient's immunity.

PMID- 18628599
TI  - Pretreatment of macrophages with the combination of IFN-gamma and IL-12 induces
      resistance to Leishmania major at the early phase of infection.
AB  - Interferon (IFN)-gamma is essential but not sufficient to control leishmaniasis.
      It is known that IFN-gamma is one of the major macrophage-activating cytokines,
      and the activated macrophages are a principal source of interleukin (IL)-12,
      which induces autocrine macrophage activation. In this study, the combined effect
      of IFN-gamma and IL-12 on the susceptibility of macrophages to Leishmania major
      infection was evaluated. Macrophages pretreated with IFN-gamma and/or IL-12 were
      infected with the parasites. Four hr post-infection (p.i.), the levels of
      infection and parasite load in the macrophages treated with the combination of
      IFN-gamma and IL-12 (IFN-gamma/IL-12) were significantly lower than those in the
      nontreated cells. However, the macrophages treated with either IFN-gamma or IL-12
      did not show resistance to L. major infection. In addition, 72 hr p.i., the IFN
      gamma/IL-12-treated and IFN-gamma-treated macrophages showed significantly lower
      levels of infection and parasite load than the nontreated cells, and higher
      levels of resistance was observed in the IFN-gamma/IL-12-treated macrophages than
      in the IFN-gamma-treated macrophages. Although IFN-gamma/IL-12 treatment of
      macrophages prior to the infection led to the induction of resistance, as
      described above, this resistance was not induced when these cytokines and the
      parasites were added simultaneously to the macrophage culture. These results
      suggest that IFN-gamma/IL-12 treatment prior to the infection restricts the early
      phase of the infection.

PMID- 18628600
TI  - Susceptibilities to antimicrobials and disinfectants in Salmonella isolates
      obtained from poultry and swine in Thailand.
AB  - Salmonella enterica isolates from poultry (n=125) and swine (n=132) in Thailand
      were investigated for antibiotic resistance, susceptibility to disinfectants
      (benzalkonium chloride (BKC), chlorhexidine digluconate (CHX), zinc chloride and
      copper sulfate) and cyclohexane tolerance. Forty-two percent were of multiple
      resistance to antibiotics. The minimum inhibitory concentrations (MICs) of all
      antibiotics against isolates from swine were higher than that against the
      isolates from poultry. There were generally few variations in MICs to all
      disinfectants, indicating that the isolates had either no or only a limited
      degree of developed resistance to the disinfectants tested. Only 5 isolates
      (1.9%) were tolerant to cyclohexane. The proton-dependent efflux systems did not
      play a major role in the reduced susceptibility to BKC and CHX, since
      susceptibility was not restored when an efflux inhibitor, carbonyl cyanide m
      chlorophenylhydrazone (CCCP) was present. Successive exposure to subinhibitory
      concentrations of BKC and CHX generated mutants resistant to BKC and CHX. A
      spontaneous BKC-resistant derivative expressed cross-resistance to antibiotics,
      chloramphenicol and erythromycin. The mechanism responsible for cross-resistance
      between BKC and antibiotics was not driven by the proton motif force (PMF).

PMID- 18628601
TI  - Genotypic change of porcine circovirus type 2 on Japanese pig farms as revealed
      by restriction fragment length polymorphism analysis.
AB  - Porcine circovirus type 2 (PCV2) has been recognized as the causal agent of
      postweaning multisystemic wasting syndrome and can be divided into two major
      genotypic groups. We developed a method of restriction fragment length
      polymorphism (RFLP) analysis of PCV2 open reading frame 2 for easy discrimination
      between the two major groups. Genotyping of PCV2 isolates from 10 Japanese
      commercial pig farms was performed, and the analysis revealed that both PCV2
      groups and at least five RFLP types of PCV2 are prevalent in Japan. On two farms,
      the genotypes of the PCV2 isolates in the spring of 2007 were different from
      those in the autumn of 2006. One genotype may have become dominant within only
      six months on these farms.

PMID- 18628602
TI  - Chemical deicer poisoning was suspected as a cause of the 2005-2006 wintertime
      mortality of small wild birds in Hokkaido.
AB  - Many small wild birds died in the 2005-2006 wintertime in Hokkaido. Thirteen
      birds were pathologically examined and it was attempted to detect West Nile and
      influenza viruses from their organs. Consecutive pathological changes were fresh
      hemorrhage and acute circulatory failure. Viral detections were negative.
      Selective occurrence in wintertime, literature review and the results of
      pathological and virological examinations suggested chemical deicer poisoning as
      the cause of wild bird death. Chicks treated orally with deicer showed acute
      death and their pathological changes were similar to those of the wild birds.
      Because the chicks showed significant elevation of plasma Na concentration,
      plasma electrolyte analysis of the affected wild birds might be crucial to
      confirm our tentative diagnosis.

PMID- 18628603
TI  - Effect of electric field in conditioned aversion response.
AB  - The aim of the present study was to estimate whether rat sense exogenous electric
      field (EF) including one used in our previous studies. Employing a conditioned
      place aversion response paradigm based on an aversive behavior against light
      environment, alteration in both voluntary behavior of Wistar rat to a 50 Hz
      sinusoidal EF was examined. Following conditioning without EF, the times spent in
      white place in rats was significantly shortened (P<0.05). While, such changes
      were not shown in rats conditioned with EF. Thus, it was considered that the
      aversion response to light environment was interfered by exposure to EF. An
      interference in recognition of brightness via EF induced effect to visual system
      or in learning system via direct effect to central nerve system was considerable
      as a factor for EF-induced effect. In addition, it was remained that rat possibly
      sense exposure to EF as preferable. In order to confirm which factor functioned,
      further studies are needed.

PMID- 18628604
TI  - A meningioma with hyperintensity on T1-weighted images in a dog.
AB  - A male six-year-old Pomeranian showed recurrent seizures and progressive left
      hemiparesis. MRI revealed a mass in the right paramedian frontal-temporal region
      with hyperintensity on T1-weighted (T1W) and mixed-intensity on T2-weighted (T2W)
      images. After gadolinium enhancement, the mass was enhanced homogenously and
      demonstrated the dural tail sign. Surgical resection of mass was performed and
      its histological diagnosis was meningioma. The meningioma of this case had a high
      cellular density with some lipid contents and intra- and extra-tumor hemorrhage,
      however, calcification was not found. These cellular characteristics may
      contribute to a higher signal intensity on T1W imaging.

PMID- 18628605
TI  - A dog with acute myelomonocytic leukemia.
AB  - A three-year-old dog with marked leukocytosis, lymphadenopathy, and diarrhea
      showed an increase in unidentified blasts in the peripheral blood, and they were
      proliferated in the bone marrow. The dog was diagnosed with myelomonocytic
      leukemia (M4) because the blast cells were demonstrated by cytochemical staining
      to be both myeloid and monocytic cells. Although the dog was treated with a multi
      combination chemotherapy and induction therapy using vitamin K2, it died on day
      47 after the first admission. This case is the first report of M4 in Japan.

PMID- 18628606
TI  - Epidemic of equine influenza among vaccinated racehorses in Japan in 2007.
AB  - On August 2007, we encountered equine influenza epidemic by Florida sub-lineage
      strain (H3N8) in Japan Racing Association's facilities where 4142 racehorses in
      total were stabled. The number of new febrile cases sharply increased, but the
      occurrence was rapidly calmed down within 2 weeks. The morbidity rate in these
      facilities was 12.8% and the subclinical infection rate of healthy racehorses
      examined by rapid antigen detection tests was 19.4% at the early stage of
      epidemic. The serological studies along with the low morbidity rate and the
      existence of numbers of asymptomatically infected racehorses, suggested that the
      cross-reactivity of the antibodies provided by vaccination against the epidemic
      strain contributed to reducing the morbidity rate and duration of epidemic.

PMID- 18628607
TI  - The prokinetic effect of mosapride citrate on horse gastric emptying rates.
AB  - The prokinetic effect of the 5-HT4 receptor agonist mosapride was evaluated in
      seven healthy thoroughbreds. Mosapride was orally administered at doses of 0.5,
      1.0 or 1.5 mg/kg. The breath 13CO2/12CO2 rate (Delta13CO2), an indirect indicator
      for the rate of gastric emptying, was measured at appropriate points for 4 hr
      after drug administration. There was a significant increase compared with the
      control value at 15, 20 and 165 min for 0.5 mg/kg, 30 min at 1.0 mg/kg and 165
      min for 1.5 mg/kg. The results suggest that mosapride may facilitate the gastric
      emptying in horses.

PMID- 18628608
TI  - Detection of Turkey astrovirus in young poults affected with poult enteritis
      complex in Brazil.
AB  - Reverse transcription polymerase chain reaction (RT-PCR) of turkey astrovirus
      (TAstV) capsid and polymerase genes was applied to the bursa of Fabricius (BF),
      thymus (TH), spleen (SP) and cloacal swabs (CS) of young poults with "Poult
      enteritis complex" (PEC). The histological lesions included atrophy, lymphoid
      depletion, cellular infiltration and necrosis of the BF, TH and SP, respectively.
      The RT-PCR reactions were positive for the polymerase gene of TAstV-2 in all 100
      CSs, 7 out of 10 of BFs and 10 out of 20 THs and SPs, respectively. Five out of
      10 THs and SPs samples, considered to be negative by RT-PCR, were positive when
      specific primers designed for the TAstV-2 capsid gene were applied. This is the
      first description of turkey astrovirus infection presenting PEC in Latin America.

PMID- 18628609
TI  - Discoid lupus erythematosus (DLE) in a Spitz dog.
AB  - A 3-year-old, female Spitz, was presented due to lack of response to therapies
      with a 6-month history of skin lesions characterized by diffuse erythema and
      scaling on the dorsal trunk. Physical examination revealed the dog was active and
      healthy. Skin culture isolated no fungus. Histological examination of skin biopsy
      specimens revealed interface dermatitis with hydropic degeneration of the basal
      layers, predominant plasmacytic perivascular accumulation in the dermis, and
      intensive plasma cell-rich interface mural folliculitis. Moderate CD3-positive
      lymphocytes infiltrated the superficial dermis. This report may provide unique
      information of canine discoid lupus erythematosus in an unusual breed with
      atypical cutaneous lesions.

PMID- 18628610
TI  - Mesojejunoileac liposarcoma with intrahepatic metastasis in a dog.
AB  - We report a liposarcoma at the mesojejunoileum that was widely excised, and then
      the intrahepatic metastatic liposarcoma was found. The dog was treated by two
      single-agent chemotherapy separately. The patient was an 8-year-old, male
      Dachshund, and was referred to our hospital owing to the significant distention
      of the left abdomen. Neither radiography nor ultrasonography detected the actual
      association of the tumor with the abdominal viscera before surgery. A large-sized
      tumor mass that adhered to the mesojejunoileum was explored by laparatomy. Final
      diagnosis of a pleomorphic liposarcoma was made by the routine histology and
      further identified by Oil Red O stain. The two single-agent chemotherapy
      including doxorubicin followed by capecitabine, however, failed to cause
      remission of the intrahepatic metastatic lesions. The patient died 22 months
      after operation and the cause of death was supposed to be metastatic liposarcoma.

PMID- 18628611
TI  - Segmental aplasia of the uterine horn with ipsilateral renal agenesis in a cat.
AB  - A nine-month-old domestic short haired cat was admitted with the history of acute
      vomiting, depression and shivering. Abdominal ultrasonography revealed minimum
      enlargement of the right uterine horn filled with anechoic fluid. On excretory
      urography, functionally and anatomically normal, enlarged left kidney was found,
      but right kidney was absent. It was preliminary diagnosed as hydrometra with
      right renal agenesis. Aiming at the correction of hydrometra, we performed
      ovariohysterectomy. During spaying, we found a missing segment of distal part of
      the right uterine horn and absence of ipsilateral kidney and ureter. Compressed
      uterine structure and segmental aplasia of right uterine horn were found in
      histopathological investigation. Taken together, it was diagnosed as a segmental
      aplasia of uterine horn with ipsilateral renal agenesis.

PMID- 18628612
TI  - Reduced immunoreactivity of tyrosine hydroxylase in the hypothalamic
      paraventricular nucleus of the seizure sensitive gerbil.
AB  - We compared the immunoreactivity and numbers of tyrosine hydroxylase (TH)
      immunoreactive neurons and neuropil in the paraventricular nucleus (PVN) of the
      hypothalamus between the seizure sensitive (SS) and seizure resistant (SR)
      gerbils. The distributional pattern of TH immunoreactivity was similar in both
      groups: TH immunoreactivity was seen mainly in magnocellular neurons of the PVN.
      However, total TH immunoreactivity in the neurons and neuropil in the SS gerbils
      was significantly lower than that in the SR gerbils. In addition, the number of
      TH immunoreactive neurons in the SS gerbils was also much lower than those in the
      SR gerbils. These results indicate that SS gerbils have a low TH immunoreactivity
      in the hypothalamic PVN compared with that in SR gerbils.

PMID- 18628613
TI  - Ubiquitin C-terminal hydrolase L1 deficiency decreases bone mineralization.
AB  - Ubiquitin C-terminal hydrolase L1 is a component of the ubiquitin proteasome
      system, which evidences unique biological activities. In this study, we report
      the pattern of UCH-L1 expression, and show that it regulates bone mineralization
      in osteogenesis. UCH-L1 was expressed in osteoblasts, osteoclasts, and
      hematopoietic precursor cells of bone marrow in the metaphysis and diaphysis of
      the femora. To further assess the involvement of UCH-L1 in the regulation of bone
      mineralization, we evaluated the bone mineral density (BMD) rate of gad mice,
      using the Latheta computed tomography system. Male gad mice evidenced a
      significantly decreased BMD rate in the metaphysis and diaphysis of the femora.
      These findings of decreased BMD rate in the bones of gad mice may suggest that
      UCH-L1 function regulates bone mineralization during osteogenesis.

PMID- 18628614
TI  - Rat RFRP-3 alters hypothalamic GHRH expression and growth hormone secretion but
      does not affect KiSS-1 gene expression or the onset of puberty in male rats.
AB  - BACKGROUND/AIMS: RFRP-3 is a recently described neuropeptide that influences a
      variety of physiologic factors, including the inhibition of gonadotropin
      secretion and reproductive behaviors. We hypothesized that endogenous RFRP-3
      could function to inhibit the onset of puberty in young male rats. METHODS: To
      test this hypothesis, we first placed cannulas into the third ventricle of 24-day
      old male rat pups. The cannulas were attached to osmotic minipumps that infused
      antisense oligonucleotides (ODNs) against RFRP-3. Second, cannulas were placed in
      the ventricle of 35-day-old pups and infused with RFRP-3, NPFF (putatively, an
      alternative transcript of the RFRP gene), or vehicle. RESULTS: No treatment
      altered the onset of puberty compared to controls. RFRP-3 ODN rats had
      significantly larger testes compared to control rats. Similarly, the RFRP-3 ODN
      treated rats had a significant increase in plasma LH, but not FSH, compared to
      control rats. Rats infused with RFRP-3 exhibited significantly smaller testes
      compared to control rats. RFRP-3 rats also had a significant decrease in plasma
      LH levels. RFRP-3 infusion elicited a significant increase in growth hormone
      releasing hormone mRNA and plasma growth hormone levels compared to control rats.
      Neither peptide had an effect on KiSS-1 mRNA expression. CONCLUSION: These data
      suggest that endogenous rat RFRP-3 does not affect the timing of puberty in male
      rats but may be associated with peripubertal rise in growth hormone secretion.

PMID- 18628615
TI  - Initiation of oral anticoagulation after acute ischaemic stroke or transient
      ischaemic attack: timing and complications of overlapping heparin or conventional
      treatment.
AB  - BACKGROUND: Oral anticoagulation is highly effective for secondary prevention of
      cardioembolic strokes in patients with atrial fibrillation (AF). There are no
      studies investigating timing and complications of different strategies for
      initiation of oral anticoagulation after acute stroke or transient ischaemic
      attack (TIA). METHODS: Patients of ten community hospitals participating in the
      prospective evaluation of medical effects of the Telemedical Project for
      Integrative Stroke Care (TEMPiS) were included. This observational evaluation was
      restricted to ischaemic stroke or TIA patients with AF who were started on
      Phenprocoumon treatment during in-hospital stay. Antithrombotic co-medication was
      dichotomized in heparin bridging (weight or partial thromboplastin time-adjusted
      heparin) or conventional treatment (antiplatelets and/or low-dose heparin or
      nil). Besides treatment-relevant extracranial bleeding, major complications were
      documented according to the European Atrial Fibrillation Trial definitions
      including vascular death, ischaemic or haemorrhagic stroke, systemic embolism,
      and myocardial infarction. RESULTS: Between July 2003 and March 2005, 4,082
      ischaemic stroke or TIA patients were admitted. AF was recorded in 961 patients
      (23.5%), of whom 376 (39.1%) received oral anticoagulation. In 229 of these
      patients oral anticoagulation was started in hospital, 150 (65.5%) with heparin
      bridging and 79 (34.5%) with conventional treatment. Patients with heparin
      bridging were younger, and had a longer in-hospital stay after adjustment for
      potential confounders (p = 0.01). Major complications were infrequent in both
      groups (2.0 vs. 2.5%; p = 1.0) as well as extracranial bleeding (3.3 vs. 1.2%; p
      = 0.43). CONCLUSIONS: Initiation of oral anticoagulation after acute ischaemic
      stroke yielded low complication rates independent of antithrombotic co
      medication. Heparin bridging was associated with a longer stay in acute care
      hospitals.

PMID- 18628616
TI  - The clinical syndrome and etiological mechanism of infarction involving the
      nucleus prepositus hypoglossi.
AB  - BACKGROUND: The human nucleus prepositus hypoglossi (NPH), which is known to be a
      neural integrator of horizontal eye movement, may also serve vestibular function.
      The present study investigated the clinical spectrum and etiological mechanism of
      isolated, small infarctions involving the NPH area demonstrated on MRI. METHODS:
      The subjects of this study were 18 consecutive patients with a small infarction
      involving the NPH that was demonstrated by diffusion-weighted MRI. We assessed
      their clinical features according to the level involved (pons or medulla
      oblongata) and determined etiological mechanisms that may cause infarction in
      this region. RESULTS: Vertigo and nausea/vomiting were the presenting symptoms in
      all patients. Sixteen patients showed truncal ataxia (contralateral falls in 11
      patients and bilateral falls in 3). Gaze-evoked nystagmus was observed in 13
      patients. In addition to those NPH-related symptoms, ipsi- lateral peripheral
      facial palsy and horizontal gaze palsies, including internuclear ophthalmoplegia
      and horizontal conjugate gaze palsy, were commonly associated with pontine
      lesions, and dysphagia was common in medullary lesions. Ten out of 18 patents
      showed significant stenosis (>or=50%) of the relevant vertebral artery. Two
      patients had aortic atheroma >4 mm, and 1 patient had atrial fibrillation.
      CONCLUSIONS: Clinical features of vertigo, contralateral falls and gaze-evoked
      nystagmus are suggestive of an NPH lesion. Accompanying signs of ipsilateral
      facial palsy of the peripheral type and/or horizontal gaze palsies are highly
      specific for a pontine NPH lesion. Large-artery atherosclerosis was the most
      common causative mechanism of infarctions involving the NPH area.

PMID- 18628617
TI  - Intra-arterial thrombolytic therapy for hyperacute ischemic stroke caused by
      tandem occlusion.
AB  - BACKGROUND: Tandem occlusion of the arteries at the extracranial and intracranial
      segments is a unique cause of ischemic stroke and is often associated with a poor
      prognosis. Although tandem occlusion is occasionally found during intra-arterial
      thrombolysis (IAT), as of yet no clear therapeutic strategy has been elucidated.
      METHODS: After identifying distal intradural (DIL) and proximal extradural
      lesions (PEL) as well as the collateral state and clot burden, IAT was performed
      primarily targeting DIL by navigation of the microcatheter through the PEL or a
      collateral pathway. RESULTS: Among 147 consecutive patients who were treated with
      IAT for hyperacute ischemic stroke, 13 (11.4%) were identified to have tandem
      occlusion as the cause of stroke. Navigation of a microcatheter through occluded
      PEL (internal carotid artery/vertebral artery) or a collateral pathway (anterior
      communicating artery) to the DIL was successful in 9 patients. Of them,
      recanalization of the DIL could be achieved in 8 (89%). The overall
      recanalization rate among all patients with tandem occlusion was (62%, 8/13). A
      good functional outcome (modified Rankin score <or=2) at 3 months was noted in 6
      patients (46.2%). CONCLUSIONS: Tandem occlusion may be successfully managed by
      strategic thrombolysis of the DIL as the primary therapeutic target for IAT. By
      this strategy, the ischemic brain could be effectively and rapidly perfused.

PMID- 18628618
TI  - Statin potentiates human platelet eNOS activity without enhancing eNOS mRNA and
      protein levels.
AB  - BACKGROUND/AIMS: Experimental studies suggest an enhanced endothelial and
      platelet nitric oxide (NO) generation after statin treatment, possibly due to
      increased endothelial NO synthase (eNOS) activity and protein levels. In parallel
      with experimental research, statins were shown to increase the forearm blood flow
      independently of serum cholesterol in humans. However, it was not possible to
      correlate blood flow changes with eNOS levels in these studies due to limitations
      in obtaining arterial samples. Hence, we investigated changes in eNOS activity,
      mRNA and protein levels after statin treatment in human platelets, which are
      readily accessible unlike arteries. METHODS: In vitro bleeding times were
      measured in 22 patients by stimulating platelets with collagen-epinephrine or
      collagen-ADP. To assess platelet eNOS activity, the bleeding times were also
      determined after incubating platelets with L-arginine. The measurements were
      repeated following 14 days of pravastatin (40 mg/day) treatment. Platelet-rich
      plasma was collected before and after statin treatment to evaluate eNOS mRNA
      (semiquantitative RT-PCR) and protein levels (Western blotting). RESULTS: The
      basal bleeding time was prolonged by 24 +/- 3% (mean +/- SE) when the samples
      were incubated with 500 microM of L-arginine. The NOS inhibitor L-N(5)-(I
      iminoethyl)ornithine reversed this effect, suggesting that it was mediated by NO.
      After statin treatment, the NO-mediated prolongation of the bleeding time with
      500 microM of L-arginine was significantly potentiated (to 44 +/- 10%). Despite
      enhanced eNOS activity, there was no significant change in platelet eNOS mRNA and
      protein levels after statin treatment. CONCLUSION: These data demonstrate that
      platelet eNOS activity is potentiated after statin treatment in humans in
      parallel with experimental studies.

PMID- 18628619
TI  - The positive effect of integrated care on depressive symptoms in stroke
      survivors.
AB  - BACKGROUND: Depressive symptoms occur in approximately one-third of stroke
      patients. We sought to evaluate whether an integrated model of stroke care and
      secondary prevention reduced depressive symptomatology in stroke survivors.
      METHODS: The integrated care (IC) model is a multifaceted program that provides
      ongoing collaboration between a specialist stroke service and primary care
      physicians, using telephone tracking, a bi-directional information feedback loop,
      management of vascular risk factors, and regular screening for depressive
      symptoms. RESULTS: Patients exposed to the IC model exhibited significantly fewer
      depressive symptoms than controls at 12 months post stroke (as measured by the
      PHQ-9 screening tool; p = 0.006). At 12 months, 30/91 (33%) of the treatment
      group had depressive symptoms, compared to 52/95 (55%) of the control group (p =
      0.003). With other variables adjusted for, the major associates of being
      depressed at 12 months were group allocation and physical disability. CONCLUSION:
      The integrated care approach provides a framework for detecting and monitoring
      depressive symptoms, and appears to be protective against post-stroke depression.

PMID- 18628620
TI  - Familial cerebral cavernous malformation: features of clinical manifestation,
      pathology and imaging in a Chinese family.

PMID- 18628621
TI  - Restoration of normal cortical excitability and gait ability in acute stroke
      after intensive rehabilitation.

PMID- 18628622
TI  - Blood pressure in acute stroke.

PMID- 18628624
TI  - Biliary tract complications after liver transplantation: a review.
AB  - Biliary complications continue to be a major cause of morbidity in liver
      transplant recipients with an incidence of 10-30% following whole-organ
      transplantation and a mortality rate of up to 10%. Biliary leaks and strictures
      are most common but sphincter of Oddi dysfunction, hemobilia, and biliary
      obstruction are also observed. Biliary complications may be related to various
      factors such as hepatic artery patency, preservation injury, cytomegalovirus
      infection, chronic ductopenic rejection, ABO incompatibility, and technical
      reasons. The latter include imperfect anastomosis, T-tube-related complications
      and the use of partial liver grafts when cut surface biliary leaks or inadvertent
      bile duct injuries may occur during parenchymal division. The usage of a T-tube
      for duct-to-duct anastomosis in whole-organ liver transplantation remains
      controversial, mainly because of the high rates of T-tube-related complications
      observed in many series. In this article we review the etiology, as well as the
      main types of biliary complications according to the technique of biliary
      reconstruction and liver transplant procedure performed. Their management is also
      discussed with interventional radiology and endoscopic techniques emerging as the
      preferred treatment option, obviating the need for surgery in a selected majority
      of patients.

PMID- 18628625
TI  - Liver infarction due to liver abscess.

PMID- 18628626
TI  - Gas gangrene of the liver after a choledocho-jejunostomy.

PMID- 18628627
TI  - Effects of diameter, number and tightness of sutures on pancreatic injury
      response.
AB  - BACKGROUND: We have experimental data indicating that the pancreas is easily
      damaged by any intervention. The present study compared the effects of suture
      diameter, number of needle passes and suture tightness on rat pancreas. METHODS:
      Under anesthesia, rat pancreas was sutured either with one loose stitch of 6-0
      polydioxanone (PDS II) or 3-0 PDS II, with 5 passes of loose running 6-0 PDS II,
      or with 6-0 PDS II loop tightened to 0.6 or 1.2 N. Amylase activity and
      pancreatic tissue histology at the suturing site and farther away, were evaluated
      1, 3, 7 and 21 days postoperatively. RESULTS: Each suturing exposure and the sham
      operation induced temporary amylase activity elevation on day 1 when compared
      with the baseline. In histology, 3-0 suture, 5 needle passes and 1.2-newton loop
      induced more damage than 6-0 suture, single needle pass and 0.6-newton loop,
      respectively. Similar but milder changes were observed in samples from the remote
      site. CONCLUSIONS: The pancreas reacts to suturing with widespread injury
      response resembling that of acute pancreatitis. In attempting to reduce suturing
      induced widespread injury, as few and thin sutures and as loose suture tightness
      as possible should be used. Although these findings may seem obvious, they have
      not previously been proven in terms of histology.

PMID- 18628628
TI  - Encephalitis lethargica in the Soviet Union.
AB  - Although encephalitis lethargica (EL) appeared in epidemic form in the Soviet
      Union during the 1920s as it did in most of the world, the Western literature,
      particularly English, contains little information about the manifestations of the
      disease there. Here we summarize articles by prominent Russian neurologists who
      wrote about the disease as they viewed it during the epidemic period. As in the
      West, Russian clinicians found EL to be remarkably polymorphic, although some
      signs and symptoms, especially those pertaining to the psychological aspects of
      the disease, seemed to be more prevalent or were described better and perhaps
      more frequently by these clinicians. Some Russian clinicians emphasized an
      increased prevalence of EL among Jews and a relationship with illness and trauma,
      whereas others found strong evidence for contagion, especially in rural areas.

PMID- 18628629
TI  - Real-life evaluations of compliance with mandatory drug safety monitoring
      exemplified with tolcapone in Parkinson's disease.
AB  - BACKGROUND/AIMS: In 1998, the European Medicines Agency suspended the approval
      for tolcapone in Parkinson's disease (PD) with motor complications due to the
      drug's implication in fulminant liver failure and the consequent death of 3
      patients. Clinical data obtained by ongoing use of tolcapone in other countries
      proved that adequate safety can be achieved if liver enzymes are strictly
      monitored. In 2005, tolcapone was relaunched in the European Union under the
      prerequisite of biweekly liver enzyme monitoring. The objective of this study was
      to evaluate the compliance with mandatory drug safety monitoring under real-life
      conditions. METHODS: Twenty-one Parkinson's disease patients receiving tolcapone
      were analyzed with regard to their compliance in performing and reporting the
      required laboratory tests. RESULTS: Tolcapone was effective and well tolerated.
      Yet, less than 25% of the patients regularly performed and reported the required
      laboratory tests and the compliance declined when comparing the first and second
      half-years of therapy. CONCLUSIONS: Our data shed light on the incongruity
      between requirements of postmarketing drug surveillance and every-day reality.
      The depicted noncompliance is most likely a general problem in postmarketing drug
      surveillance with an impact for physicians, manufacturers and legal authorities.
      Practical, legal and ethical aspects will be discussed.

PMID- 18628630
TI  - Stenting of symptomatic basilar and vertebral artery stenosis in patients
      resistant to optimal medical prevention: the lyon stroke unit experience.
AB  - Intracranial angioplasty stenting may be an efficient therapy in patients with
      intracranial atherosclerotic symptomatic vertebrobasilar artery stenosis
      unresponsive to optimal medical therapy. We present our experience in this
      setting. RESULTS: The study included 12 cases (8 men, 4 women), with an age range
      of 43-78 years (mean 62.6 years). Intracranial stenosis that resulted in
      qualifying stroke or transient ischemic attack involved the vertebral artery (n =
      4), lower basilar artery (n = 1) and mid basilar artery (n = 5). Tandem stenosis
      included the intracranial vertebral artery and basilar artery (n = 1) and both
      intracranial vertebral arteries (n = 1). The degree of stenosis ranged between 70
      and 90% in the basilar and vertebral arteries. Angioplasty + stenting was
      performed in all lesions. A successful procedure resulting in 30% of residual
      stenosis was found in 14 vessels. A periprocedural adverse event occurred in 1
      case and was related to a brain hemorrhage. The mean patient follow-up was 15 +/-
      3 months; 10 patients remained symptom free. All patients underwent a
      percutaneous endovascular balloon angioplasty and stent placement. CONCLUSIONS:
      This study supports the safety and the potential efficiency of stent-assisted
      angioplasty in patients resistant to optimal prevention. Randomized larger
      prospective trials are needed to confirm the benefit of this approach.

PMID- 18628631
TI  - Elevation of cerebrospinal fluid protein in patients with diabetes mellitus is
      associated with duration of diabetes.
AB  - We investigated the relationships between total cerebrospinal fluid (CSF) protein
      in diabetic patients and the clinical characteristics of diabetes mellitus. The
      subjects comprised 16 diabetic patients (median age = 60.5 years, range = 47-71)
      who were studied retrospectively. Patients with diseases known to be associated
      with increases in total CSF protein were excluded as far as possible. The median
      total CSF protein and albumin quotient in the diabetic group were 52.5 mg/dl
      (range = 41-84) and 6.13 x 10(-3) (range = 4.0 x 10(-3) to 13.1 x 10(-3)),
      respectively. These results were significantly higher than those in 28 age
      matched nondiabetic patients (median = 59.0 years, range = 50-71) (p < 0.01).
      Duration of diabetes was associated with total CSF protein (r = 0.642, p < 0.01).
      If the CSF shows increased total protein in a diabetic patient who has not
      suffered from long-term diabetes (> or =5 years), causes other than diabetes
      should be considered to explain increases in total CSF protein. We need to
      confirm the present results by studying a larger population of diabetic patients.

PMID- 18628632
TI  - Neurological and MRI findings as predictors of progressive-type lacunar
      infarction.
AB  - AIMS: To find neurological or neuroimaging signs to predict neurological
      deterioration in acute lacunar infarctions. METHODS: Sixty-one consecutive
      patients with a supratentorial lacunar infarct, who were admitted within 48 h,
      were studied retrospectively. Progressive-type stroke (PS) was defined as
      progressive motor deficits that arose within 7 days after onset, by using the
      motor ratings of the National Institutes of Health Stroke Scale. RESULTS: Sixteen
      patients (26%) were classified into the PS group. In the PS group, fluctuating or
      progressing onset (81 vs. 42%, p = 0.009), leg-predominant motor deficits on
      admission (63 vs. 16%, p = 0.001) and corona radiata lesion on diffusion-weighted
      MRI (100 vs. 69%, p = 0.013) were all more frequent than in the non-PS group.
      CONCLUSION: Bedside neurological assessment and MRI findings may allow us to
      predict PS and start early intensive treatment for preventing further
      neurological deterioration.

PMID- 18628633
TI  - Adherence and quality of oral anticoagulation in cerebrovascular disease patients
      with atrial fibrillation.
AB  - BACKGROUND/AIMS: Low rates and poor quality of oral anticoagulation (OAC) have
      been reported in patients with atrial fibrillation (AF). We therefore sought to
      investigate the prescription patterns at discharge, adherence and quality of OAC
      in cerebrovascular disease patients with AF. METHODS: Consecutive ischemic stroke
      (IS) and transient ischemic attack (TIA) patients were prospectively documented
      in 11 German stroke centers. A central telephone follow-up after 1-2 years
      assessed the current antithrombotic medication and results of coagulation checks.
      RESULTS: Of 1,463 surviving patients with AF, 30.5% were discharged on OAC and
      13.9% on high-dose heparin. Of 329 AF patients discharged on OAC and with consent
      for follow-up, 88.7% of surviving patients were still on OAC at the follow-up. Of
      these, 52.7% reported coagulation values out of the therapeutic range during the
      preceding 3 months. A recurrent IS was seen in 9 patients (2.1%/year) and an
      intracranial hemorrhage in 2. CONCLUSION: We found an important underuse of OAC
      following TIA or IS mainly in older patients and with greater stroke-related
      disability. Although the reported coagulation checks showed an only moderate rate
      within therapeutic ranges, safety and efficacy of OAC in this cohort seem
      comparable to previous randomized and observational trials in AF patients.

PMID- 18628634
TI  - Cognitive impairment in late-onset depression. Limited to a decrement in
      information processing resources?
AB  - BACKGROUND: While cognitive dysfunction in late-onset depression (LOD) is common,
      the nature and determinants of this impairment are heterogeneous. It has been
      suggested that neuropsychological decrements in LOD patients might result from a
      deficit in processing resources. In order to address this issue, we analyzed
      processing resources in LOD to see if their decrease explains higher-level
      cognition (episodic memory and naming capacity) deficits. METHODS: Measures of
      processing speed, working memory, inhibition, episodic memory and naming capacity
      were administered to 14 LOD inpatients and 14 controls. RESULTS: The LOD patients
      performed significantly worse than the controls in all domains except for
      inhibition. Hierarchical regression analyses showed that naming capacity
      impairment was totally mediated by processing speed and working memory, whereas
      episodic memory dysfunction was only partially mediated by working memory.
      CONCLUSION: The reduction in certain processing resources (working memory,
      processing speed) in late-onset depressed patients appears to mediate impairments
      in episodic memory and naming capacity. However, episodic memory impairment
      cannot only be explained by processing resource decrement in LOD patients,
      suggesting that a primary episodic memory dysfunction is present in this
      condition.

PMID- 18628636
TI  - Corneal hysteresis and corneal resistance factor in keratoectasia: findings using
      the Reichert ocular response analyzer.
AB  - AIM: To examine corneal hysteresis (CH) and corneal resistance factor (CRF) in
      normal and ectatic corneas. METHODS: CH and CRF were measured using the Reichert
      Ocular Response Analyzer in patients with clinically diagnosed keratoconus (KC),
      forme fruste KC (FFKC) and normal eyes. RESULTS: 21 eyes (13 patients) with
      clinically diagnosed KC and 30 eyes (18 patients) with FFKC were included in the
      study. Mean CH and CRF in FFKC did not differ from that in pachymetry-matched
      normal eyes. KC eyes had significantly lower CH and CRF than normal and FFKC
      eyes. CONCLUSION: A significant overlap in CH and CRF values among the 3 groups
      was evident. Our findings do not indicate a role for CH and CRF measurement as a
      single test to aid in the detection of early ectasia. It may be of use when used
      in conjunction with other parameters such as aberrometry. CH and CRF values may
      prove to be useful in monitoring ectasia progression.

PMID- 18628637
TI  - [Reconstruction of the head and neck with free osteoseptocutaneous flap in
      elderly heavy smokers].
AB  - OBJECTIVES: We evaluated complications of free flap reconstruction following
      oncological head and neck surgery in elderly patients who smoked heavily.
      PATIENTS AND METHODS: The study included eight patients (2 females, 6 males; mean
      age 68.5 years; range 65 to 74 years) over 65 years of age, who smoked heavily
      (at least 1 pack/day). All cases but one with mandibular ameloblastoma had
      intraoral squamous cell carcinoma. Two patients underwent reconstruction with
      free radial forearm osteoseptocutaneous flap following bilateral maxillary
      resection, and six patients with free fibular osteoseptocutaneous flap following
      mandibular resection. Postoperative complications, in particular those associated
      with the donor and recipient sites were evaluated. RESULTS: No partial or total
      flap loss was observed. Wound healing problems were seen in three patients (37%),
      which were at the donor site in two patients, and at the recipient site in one
      patient. Psychogenic disorders were observed in two patients (25%). No other
      complications were encountered. CONCLUSION: Aside from some recipient- and donor
      site-related healing problems, heavy smoking and advanced age cannot be regarded
      as contraindications for free flap reconstruction.

PMID- 18628638
TI  - [Endoscopic adenoidectomy].
AB  - OBJECTIVES: This study evaluated endoscopic adenoidectomy operations performed in
      children for hypertrophic adenoid tissue in the nasopharynx. PATIENTS AND
      METHODS: A total of 125 patients (67 boys, 58 girls; mean age 4.8+/-2.4 years;
      range 2 to 15 years) underwent endoscopic adenoidectomy under general anesthesia
      for one or more of the following complaints: nasal obstruction, mouth breathing,
      snoring, loss of appetite, slower development than peers, and decreased hearing.
      Preoperatively, 48 patients were eligible for endoscopic rhinoscopy, which showed
      an adenoid mass causing total or almost total obstruction of the nasal passage.
      In the remaining patients, lateral cranial radiographs showed a mass narrowing
      the air passage in the nasopharynx. Postoperative controls were carried out at
      one and four weeks by physical examination and an inquiry into the patients'
      satisfaction. In addition, endoscopic rhinoscopy was performed in the fourth week
      in eligible patients. Final controls were carried out at the end of the second
      year. RESULTS: At the end four weeks, none of the patients had nasal obstruction
      or related complaints. Postoperative endoscopic rhinoscopy performed in 39
      patients showed almost complete removal of adenoid tissues. None of the patients
      exhibited recurrent adenoid hypertrophy at the end of two years. CONCLUSION:
      Hypertrophic adenoid tissue in the nasopharynx, especially those encroaching on
      the nasal cavity, can be removed completely under direct endoscopic
      visualization. Endoscopic adenoidectomy is a more satisfactory method than
      conventional adenoidectomy, because it allows control of how much adenoid tissue
      is removed.

PMID- 18628639
TI  - [Reduction of the inferior turbinates with a microdebrider].
AB  - OBJECTIVES: We evaluated the results of submucosal microdebrider turbinate
      reduction in patients with inferior turbinate hypertrophy. PATIENTS AND METHODS:
      The study included 503 patients (190 females, 313 males; mean age 28 years; range
      18-68 years) who underwent turbinate reduction by a microdebrider for inferior
      turbinate hypertrophy. The inferior turbinates were examined by anterior
      rhinoscopy and nasal endoscopy before and three weeks after surgery and their
      size was graded from I to III. Preoperatively, 384 patients had grade II, 119
      patients had grade III inferior turbinates. Of the study group, 116 patients
      completed a follow-up of two years. RESULTS: At three weeks after surgery, none
      of the patients had grade III turbinates; 435 patients and 68 patients were
      evaluated as grade I and II, respectively. At the end of two years, none had
      grade III turbinates; 76 patients were grade I, 40 patients were grade II.
      Complaints of nasal obstruction disappeared in three weeks in 95% of patients and
      it did not recur in all 116 patients at the end of two years. In the early
      postoperative period, crusting was not observed and recovery was quick. The most
      common complication was mucosal tears (n=114, 22.6%). Bleeding was seen in only
      one patient (0.2%). CONCLUSION: Submucosal microdebrider turbinate reduction is a
      safe alternative procedure and provides rapid healing with low complication
      rates, especially postoperative crusting.

PMID- 18628640
TI  - [Endoscopic approach in patients with choanal polyps].
AB  - OBJECTIVES: We evaluated the results of endoscopic treatment for choanal polyps.
      PATIENTS AND METHODS: Twelve patients (5 females, 7 males; mean age 25 years;
      range 10 to 49 years) underwent endoscopic surgery for choanal polyps.
      Preoperatively, all the patients were evaluated with endoscopic nasal cavity and
      nasopharyngeal examination and computed tomography of the paranasal sinuses. In
      addition, serum total and specific IgE levels were measured and prick test was
      performed. There were seven antrochoanal (58%), two ethmochoanal (17%), two
      sphenochoanal polyps, and one patient (8%) had a chonchachoanal polyp. Anterior
      ethmoidectomy and intranasal polypectomy were performed for ethmochoanal and
      sphenochoanal polyps, respectively. Two patients in whom antral part of the
      mucosa could not be clearly determined underwent transcanine sinoscopy. In all
      the patients, the mucosa giving rise to polyps was removed. Evaluations were made
      at one and six months and at the end of a year. RESULTS: The most common symptoms
      were nasal obstruction (70%) and nasal discharge (52%). Allergic tests were
      positive in two patients with antrochoanal polyps. The only complication was mild
      bleeding in two patients. No recurrences were encountered within a year follow
      up. CONCLUSION: Endoscopic approach for choanal polyps can be applied at all ages
      and it is associated with low morbidity.

PMID- 18628641
TI  - [The results of specific immunotherapy for house dust mites in patients with
      allergic rhinitis].
AB  - OBJECTIVES: We evaluated three-year clinical and laboratory results of specific
      immunotherapy (SIT) for allergenic house dust mite species, Dermatophagoides
      pteronyssinus and D. farinae. PATIENTS AND METHODS: The study included 26
      patients (6 males, 20 females; mean age 28 years; range 17-56 years) who had
      allergic rhinitis and were found to be sensitive to D. pteronyssinus and D.
      farinae. Due to unresponsiveness to other treatment modalities, the patients
      received subcutaneous SIT for three years. Symptoms (nasal stuffiness,
      rhinorrhea, itching, sneezing, headache, eye symptoms, and smelling) were graded
      before and at the end of SIT, and blood eosinophilia, total IgE and specific IgE
      levels were determined. RESULTS: At the end of three years, the number of
      patients that showed strong positivity to D. pteronyssinus and D. farinae
      decreased from 26 (100%) to 3 (11.5%) (p=0.0001) and from 18 (69.3%) to 4 (15.4%)
      (p<0.005), respectively. There were significant decreases in blood eosinophilia,
      total IgE and specific IgE levels, and in the severity of all symptoms related to
      the nose, head, and eye. CONCLUSION: Specific immunotherapy reduces symptoms in
      patients with allergic rhinitis. It is an effective treatment method for allergic
      rhinitis if performed by trained physicians in carefully selected patients.

PMID- 18628643
TI  - [The efficacy of radiofrequency ablation technique in patients with inferior
      turbinate hypertrophy].
AB  - OBJECTIVES: The efficacy of the radiofrequency ablation technique was evaluated
      in patients with nasal airway obstruction due to inferior turbinate hypertrophy.
      PATIENTS AND METHODS: The study included 30 patients (20 females, 10 males; mean
      age 32+/-12 years; range 17 to 18 years) treated with radiofrequency ablation.
      The patients were evaluated preoperatively and at 3, 7, and 60 days for nasal
      obstruction, turbinate edema, and other complaints using a visual analog scale
      (VAS). Nasal ciliary activity was evaluated by the saccharin test at 7 and 60
      days, and nasal volume was measured by acoustic rhinometry at 60 days. RESULTS:
      Postoperative VAS scores of nasal obstruction, nasal itching, crusting, sneezing,
      rhinolalia, nasal discharge, and post-nasal drip significantly decreased
      (p<0.05), while hyposmia score remained unchanged. Postoperative pain was trivial
      and did not require analgesic use. Nasal passage volume increased significantly
      (p<0.05). Nasal ciliary activity did not change significantly. No significant
      episodes of epistaxis were observed postoperatively. CONCLUSION: Radiofrequency
      ablation may be the treatment of choice for turbinate reduction because it is
      highly effective, minimally invasive with very low complication rates, and can be
      performed in outpatient clinics without general anesthesia.

PMID- 18628642
TI  - [Investigation of Helicobacter pylori colonization in pharyngeal and palatine
      tonsils with rapid urease test and immunohistochemical analysis].
AB  - OBJECTIVES: We investigated the presence and frequency of Helicobacter pylori in
      palatine and pharyngeal tonsil tissues of children. PATIENTS AND METHODS: The
      study included 20 patients (15 males, 5 females; mean age 8.2 years; range 5 to
      13 years) with chronic or recurrent tonsillitis and/or snoring. Of these, 17
      patients underwent adenoidectomy and tonsillectomy, two patients underwent
      adenoidectomy and tonsillectomy with bilateral ventilation tube insertion, and
      one patient underwent adenoidectomy with bilateral ventilation tube insertion. H.
      pylori colonization was sought in all tonsillar specimens by rapid urease test
      and immunohistochemical analysis. RESULTS: Rapid urease test showed H. pylori
      colonization in the palatine and pharyngeal tonsil specimens of one patient (5%),
      whereas immunohistochemical analysis showed four H. pylori-positive patients
      (20%), whose pharyngeal tonsil (n=2) or palatine tonsil (n=2) specimens were
      individually affected. CONCLUSION: The presence of H. pylori in both palatine and
      pharyngeal tonsil tissues of children suggests that these tissues can be a
      reservoir for H. pylori.

PMID- 18628644
TI  - [Internal jugular venous thrombophlebitis secondary to tooth extraction].
AB  - A 20-year-old female patient presented with swelling and pain in the neck,
      difficulty in opening her mouth, dyspnea, nausea, fever, and shivering. She was
      prescribed amoxicillin for one week due to a teeth infection and had lower molar
      tooth extraction on the same side two days before. Neck examination showed a
      swelling, 2 x 3 cm in size, in the carotid triangle and minimal hyperemia on the
      skin. A diagnosis of internal jugular venous thrombophlebitis was made and
      parenteral antibiotherapy was administered along with antithrombotic therapy.
      Complete improvement was observed after 15 days and the patient was symptomless
      in the eighth month.

PMID- 18628645
TI  - [Pseudoaneurysm of the internal carotid artery following a tonsil biopsy:
      endovascular repair with covered stent].
AB  - Evaluation and management of peritonsillar masses require specific attention
      because of their relationship to vital neighboring anatomical structures. A 57
      year-old woman developed pseudoaneurysm of the internal carotid artery following
      a biopsy taken at another center from a mass in the left tonsillar region. She
      was treated by a multidisciplinary approach and an endovascular covered stent was
      implanted under local anesthesia in the left internal carotid artery. No
      recurrence was detected in the neck and the patient was asymptomatic in the
      postoperative second year.

PMID- 18628646
TI  - Tracheo-innominate artery fistula in a laryngectomized patient.
AB  - Tracheo-innominate artery fistula is a rare but usually fatal complication of
      tracheostomy or intubation. To our knowledge, this complication has been reported
      following laryngectomy only in two patients. A 45-year-old woman with hypopharynx
      carcinoma developed tracheo-innominate artery fistula one month after total
      laryngopharyngoesophagectomy, as a complication of permanent tracheostomy,
      induced by the erroneous use of a 12-mm diameter silver tracheostomy cannula.
      With a median sternotomy, the innominate artery was reconstructed with Gore-Tex
      vascular graft interposition and separated from the trachea by a pedicled
      pericardial patch. Unfortunately, the patient sustained intermittent
      postoperative hemorrhages due to mediastinitis and died on the 15th day. After
      this tragic result, our attention was focused on both prevention of tracheo
      innominate artery fistulas and methods of preventing and dealing with
      hemorrhages.

PMID- 18628647
TI  - Rosai-Dorfman disease presenting as laryngeal masses.
AB  - Extranodal lesions may be the sole manifestation of Rosai-Dorfman disease (RDD).
      Although the head and neck region is one of the most common extranodal sites,
      laryngeal involvement is very rare. A 44-year-old woman presented with a
      complaint of progressive dyspnea. She had a three-year history of treatment for
      asthma and a history of operation for a nasal mass that afflicted her for 15
      years and was diagnosed as rhinoscleroma. On physical examination, she had three
      subcutaneous lesions, in the left lower eyelid, right epicanthal area, and left
      forearm, respectively. No lymphadenopathy was present. Laryngoscopic examination
      revealed three solid, polypoid masses in the subglottic region, 1 cm in diameter.
      With a two-staged operation, the laryngeal masses were excised totally together
      with the subcutaneous lesions. Histological examination of all the specimens
      showed proliferation of histiocytes. Immunohistochemical staining revealed
      typical S-100 protein-positive histiocytes and emperipolesis. Both laryngeal and
      subcutaneous lesions were diagnosed as RDD. A re-evaluation of sections from the
      previous operation specimen of the nasal mass showed the same morphological
      features. The patient was healthy without recurrence, nine months following
      surgery.

PMID- 18628648
TI  - Facial paralysis due to an occult parotid abscess.
AB  - Facial paralysis associated with benign diseases of the parotid gland is very
      rare. It has been reported in approximately 16 cases of acute suppurative
      parotitis or parotid abscess. We presented a 45-year-old woman who developed
      facial paralysis secondary to an occult parotid abscess. Initially, there was no
      facial paralysis and the signs and symptoms were suggestive of acute parotitis,
      for which medical treatment was initiated. Three days later, left-sided facial
      palsy of HB (House-Brackmann) grade 5 developed. Ultrasonography revealed a
      pretragal, hypoechoic mass, 10x8 mm in size, causing inflammation in the
      surrounding tissue. Fine needle aspiration biopsy obtained from the mass revealed
      polymorphonuclear leukocytes and lymphocytes. No malignant cells were observed.
      The lesion was diagnosed as an occult parotid abscess. After a week, the mass
      disappeared and facial paralysis improved to HB grade 4. At the end of the first
      month, facial paralysis improved to HB grade 1. At three months, facial nerve
      function was nearly normal.

PMID- 18628649
TI  - [Type I Chiari malformation presenting with isolated unilateral hypoglossal nerve
      and vocal cord paralysis].
AB  - Chiari malformation refers to caudal displacement of posterior fossa structures
      through the foramen magnum in the cervical canal and is classified according to
      the severity of displacement and accompanying cranial nerve and cervical
      pathologies. We presented a 24-year-old male patient who had isolated unilateral
      paralysis of the hypoglossal nerve and vagus nerve, with thyroid cartilage
      asymmetry. Chiari type I malformation was diagnosed by craniospinal magnetic
      resonance imaging. Suboccipital craniectomy and cervical 1-level large partial
      laminectomy were performed by the neurosurgery department. No improvement was
      observed in hypoglossal and vagal paralysis during an 18-month follow-up.

PMID- 18628650
TI  - Autophagy protects renal tubular cells against cyclosporine toxicity.
AB  - A major side effect of the powerful immunosuppressive drug cyclosporine (CsA) is
      the development of a chronic nephrotoxicity whose mechanisms are not fully
      understood. Recent data suggest that tubular cells play a central role in the
      pathogenesis of chronic nephropathies. We have shown that CsA is responsible for
      endoplasmic reticulum (ER) stress in tubular cells. Autophagy has recently been
      described to be induced by ER stress and to alleviate its deleterious effects. In
      this study, we demonstrate that CsA induces autophagy in primary cultured human
      renal tubular cells through LC3II expression and autophagosomes visualization by
      electron microscopy. Autophagy is dependant on ER stress because various ER
      stress inducers activate autophagy, and salubrinal, an inhibitor of eIF2alpha
      dephosphorylation that protects cells against ER stress, inhibited LC3II
      expression. Furthermore, autophagy inhibition during CsA treatment with beclin1
      siRNA significantly increases tubular cell death. Finally, immunohistochemical
      analysis of rat kidneys demonstrates a positive LC3 staining on injured tubular
      cells, suggesting that CsA induces autophagy in vivo. Taken together, these
      results demonstrate that CsA, through ER stress induction, activates autophagy as
      a protection against cell death.

PMID- 18628652
TI  - Arterial stiffness: a modifiable cardiovascular risk factor?
AB  - The subject of arterial stiffness as a modifiable risk factor is controversial
      and difficult to understand. The best approach here will be to assist readers to
      understand the issue and the basis of controversy. We also hope to show that the
      subject is not as overwhelming as it might appear. We believe that new blood is
      required in this field and that a basic understanding is necessary for
      researchers to be induced to take on such investigations. Our approach sets out a
      historic and pathophysiologic background on which modern studies can be based;
      describes measures and indices of arterial stiffness including pulse wave
      velocity, augmentation index, ambulatory arterial stiffness index, aortic
      impedance, and carotid elastic modulus; and finally, addresses the specifics of
      this interesting and important question. Although aortic stiffening with age is
      attributable to fracture of elastin lamellae and is largely irreversible,
      stiffening of muscular arteries can be modified by vasodilator drugs, and by
      improved endothelial function such as induced by exercise training.

PMID- 18628653
TI  - Upper-body progressive resistance training improves strength and household
      physical activity performance in women attending cardiac rehabilitation.
AB  - PURPOSE: The purpose of this study was to examine the impact of moderate
      intensity, progressive, upper-body resistance training (RT) on muscle strength
      and perceived performance of household physical activities (HPA) among women in
      cardiac rehabilitation. METHODS: The 10-week, pretest-posttest, experiment
      randomized women to either usual care (UC) aerobic exercise or RT. Muscle
      strength for 5 upper-body RT exercises (chest press, shoulder press, biceps curl,
      lateral row, and triceps extension) was measured using the 1-Repetition Maximum
      Assessment. The RT group progressively increased weight lifted using 40%, 50%,
      and 60% of obtained 1-Repetition Maximum Assessment at 3-week intervals.
      Perceived performance of HPA was measured with the Kimble Household Activities
      Scale. RESULTS: The RT group (n = 16, mean age 64 +/- 11) significantly increased
      muscle strength in all 5 exercises in comparison with the UC group (n = 14, mean
      age 65 +/- 10) (chest press, 18% vs 11%; shoulder press, 24% vs 14%; biceps curl,
      21% vs 12%; lateral row, 32% vs 9%; and triceps extension, 28% vs 20%,
      respectively). By study end, Household Activities Scale scores significantly
      increased (F = 13.878, P = .001) in the RT group (8.75 +/- 3.19 vs 11.25 +/-
      2.14), whereas scores in the UC group decreased (8.60 +/- 3.11 vs 6.86 +/- 4.13).
      CONCLUSION: Progressive upper-body RT in women shows promise as an effective tool
      to increase muscle strength and improve the ability to perform HPA after a
      cardiac event. Beginning RT early after a cardiac event in a monitored cardiac
      rehabilitation environment can maximize the strengthening benefit.

PMID- 18628655
TI  - Factors affecting cardiac rehabilitation referral by physician specialty.
AB  - PURPOSE: Cardiac rehabilitation (CR) is widely underutilized because of multiple
      factors including physician referral practices. Previous research has shown CR
      referral varies by type of provider, with cardiologists more likely to refer than
      primary care physicians. The objective of this study was to compare factors
      affecting CR referral in primary care physicians versus cardiac specialists.
      METHODS: A cross-sectional survey of a stratified random sample of 510 primary
      care physicians and cardiac specialists (cardiologists or cardiovascular
      surgeons) in Ontario identified through the Canadian Medical Directory Online was
      administered. One hundred four primary care physicians and 81 cardiac specialists
      responded to the 26-item investigator-generated survey examining medical,
      demographic, attitudinal, and health system factors affecting CR referral.
      RESULTS: Primary care physicians were more likely to endorse lack of familiarity
      with CR site locations (P < .001), lack of standardized referral forms (P <
      .001), inconvenience (P = .04), program quality (P = .004), and lack of discharge
      communication from CR (P = .001) as factors negatively impacting CR referral
      practices than cardiac specialists. Cardiac specialists were significantly more
      likely to perceive that their colleagues and department would regularly refer
      patients to CR than primary care physicians (P < .001). CONCLUSIONS: Where
      differences emerged, primary care physicians were more likely to perceive factors
      that would impede CR referral, some of which are modifiable. Marketing CR site
      locations, provision of standardized referral forms, and ensuring discharge
      summaries are communicated to primary care physicians may improve their
      willingness to refer to CR.

PMID- 18628656
TI  - Six-minute walk test in patients with permanent cardiac pacemakers.
AB  - PURPOSE: The 6-minute walk test (6MWT) is a simple and reliable method routinely
      used in the evaluation of many conditions including cardiac diseases. However, it
      is rarely performed in patients with pacemakers (PMs), and the applicability and
      safety in this group is not established. The purpose of this study was to verify
      the applicability and safety of the 6MWT in the evaluation of functional capacity
      of patients with PMs, considering the ergometry test (ET) as the criterion
      standard. METHODS: Twenty-four patients with rate-responsive PMs underwent a
      treadmill ET, using the Chronotropic Assessment Exercise Protocol, and a 6MWT,
      performed twice with a rest interval of 20 minutes. Functional capacity, heart
      rate, and blood pressure in each test were recorded. RESULTS: The distance
      covered during the 6MWT significantly correlated with the oxygen uptake estimated
      from the treadmill ET (r = 0.709, P < .001). Peak heart rates and systolic blood
      pressure levels reached during the 2 tests were also significantly correlated. No
      adverse events or malignant arrhythmias were observed during the 6MWT. The
      distance walked during the 6MWT accurately predicted the patient performance on
      the ET (area under the receiver operating characteristic curve = 0.921). The
      ability to walk more than 538 m in the 6MWT predicted, with a sensitivity of 90%
      and a specificity of 79%, an estimated oxygen uptake above 10 metabolic
      equivalents (METs) on the ET. CONCLUSIONS: The 6MWT can be considered safe to
      assess the submaximal functional capacity and can be used as an alternative test
      to evaluate the results of interventions in patients with permanent cardiac PMs.

PMID- 18628657
TI  - Effect of Ginkgo biloba (EGb 761) on treadmill walking time among adults with
      peripheral artery disease: a randomized clinical trial.
AB  - PURPOSE: Medical therapies for treatment of peripheral artery disease (PAD) are
      limited. Ginkgo biloba has been reported to increase maximal and pain-free
      walking distance among patients with PAD; however, the evidence is inconsistent.
      The objective of this study was to compare the effects of 300 mg/d of Ginkgo
      biloba (EGb 761) versus placebo on treadmill walking time and related
      cardiovascular measures among patients with PAD. METHODS: A double-blind, placebo
      controlled, parallel design trial with a 4-month duration was used. Participants
      were 62 adults, aged 70 +/- 8 years (mean +/- SD), with claudication symptoms of
      PAD. The primary study outcomes were maximal and pain-free walking time on a
      treadmill. Secondary outcomes included flow-mediated vasodilation, a measure of
      antioxidant status as assessed by determining antibody levels to epitopes of
      oxidized low-density lipoprotein, and questionnaires addressing walking
      impairment and quality of life. RESULTS: Maximal treadmill walking time increased
      by 20 +/- 80 and 91 +/- 242 seconds in the placebo and the EGb 761 groups,
      respectively (P = .12). Pain-free walking time increased by 15 +/- 31 and 21 +/-
      43 seconds, respectively (P = .28). No significant differences were detected
      between groups for any of the secondary outcomes. CONCLUSIONS: In older adults
      with PAD, Ginkgo biloba produced a modest but insignificant increase in maximal
      treadmill walking time and flow-mediated vasodilation. These data do not support
      the use of Ginkgo biloba as an effective therapy for PAD, although a longer
      duration of use should be considered in any future trials.

PMID- 18628659
TI  - Characterization of umami receptor and coupling G protein in mouse taste cells.
AB  - Taste receptor cells (TRCs) express multiple umami receptors. We performed
      physiological investigations to determine whether umami-responding cells in taste
      buds possess G protein-coupled receptors and to determine what type of G proteins
      exist if any. To clarify the components that participate in intracellular umami
      signal transduction in mouse, we recorded the activation of TRCs. TRCs treated
      with the G protein inhibitor GDP-beta-S lost umami-induced inward currents.
      Treatment with the Galphai inhibitor, pertussis toxin, did not increase the
      intracellular Ca2+ level in many TRCs. Immunohistochemical analysis revealed that
      a subset of TRCs responding to umami stimuli expressed alpha-gustducin. Thus, we
      demonstrated that umami stimuli were received by G protein-coupled receptors that
      function together with some of the Galphai family members.

PMID- 18628660
TI  - Leucine-rich glioma inactivated 3 is involved in amyloid beta peptide uptake by
      astrocytes and endocytosis itself.
AB  - We earlier showed that leucine-rich glioma inactivated 3 (LGI3) colocalizes with
      amyloid beta peptide (Abeta) taken up by astrocytes both in vitro and in vivo,
      and that LGI3 accumulated with endocytosis-associated proteins in aged monkey
      brains. In this study, we confirmed that LGI3 localizes to the endocytic pathway
      and found that its accumulation is caused by endocytic perturbation. Most
      notably, RNA interference experiments demonstrated that the downregulation of
      LGI3 clearly inhibited Abeta uptake by cultured rat astrocytes, moreover,
      transferrin uptake by both astrocytes and neuronal cells. Together with our
      earlier findings, our results suggest that LGI3 is involved in Abeta uptake by
      astrocytes and even endocytosis itself.

PMID- 18628661
TI  - Differential brain activation in anorexia nervosa to Fat and Thin words during a
      Stroop task.
AB  - We measured brain activation in six anorexia nervosa patients and six healthy
      controls performing a novel emotional Stroop task using Fat, Thin, and Neutral
      words, and words made of XXXXs. Reaction times increased in the patient group in
      Thin and Fat conditions. In the Thin-XXXX contrast, patients showed greater
      activation than controls at the junction of left insula, frontal and temporal
      lobes and in left middle and medial frontal gyri. In the Fat-XXXX contrast,
      controls showed greater activation in left dorsolateral prefrontal cortex and
      right parietal areas. Mechanisms underlying attentional bias in anorexia nervosa
      likely differ under conditions of positive and negative valence. This paradigm is
      a promising tool to examine neural mediation of emotional response in anorexia
      nervosa.

PMID- 18628662
TI  - Th1 cytokines are upregulated by adenoviral vectors in the brains of primed mice.
AB  - A major disadvantage of first generation adenoviral vectors for gene therapy in
      the brain is the immune response they elicit. Human adenovirus is a common
      respiratory virus and earlier exposure to it has important implications for gene
      therapy. We show that the immune response against E1-deleted adenoviral vectors
      in the brain is more deleterious in animals previously exposed to the virus.
      Analysis of cytokine mRNA revealed enhanced and prolonged upregulation of the Th1
      proinflammatory cytokines, IFN-gamma, TNF-alpha and IL-12 whereas, effects on Th2
      cytokines were negligible. This was associated with reduced reporter gene
      expression, decreased expression of the dopamine transporter protein and
      demyelination. This knowledge of the molecular regulation of the immune response
      provides insight into targets, which could be manipulated to reduce inflammation
      in immunologically primed animals.

PMID- 18628663
TI  - Characterization of subcellular localization and Ca2+ modulation of
      calsenilin/DREAM/KChIP3.
AB  - Earlier reports found that calsenilin is a transcriptional repressor or a subunit
      of plasma membrane channel, and indicated that calsenilin was present in the
      nucleus or plasma membrane. Immunohistochemical and subcellular fractionation
      analysis, however, revealed that calsenilin/DREAM/KChIP3 was distributed
      throughout the cytoplasm of SK-N-BE2(C), Jurkat, and HeLa cells. In addition, the
      expression of calsenilin suppressed the ATP-induced increase in intracellular
      Ca2+ concentrations. By increase in intracellular calcium concentration,
      calsenilin was translocated into the nucleus.

PMID- 18628664
TI  - Relative telomere length in patients with late-onset Alzheimer's dementia or
      vascular dementia.
AB  - Telomeres generally shorten with age. An accelerated shortening of the telomeres
      has been linked to several age-related disorders. We hypothesized that the
      relative length of telomeres could discriminate between patients with late-onset
      Alzheimer's disease (AD) and vascular dementia (VaD). A quantitative real-time
      PCR method was used to calculate the relative telomere length in 76 age-matched
      and sex-matched, newly diagnosed late-onset AD or VaD patients recruited from our
      Memory Unit. No significant difference was found in the relative telomere length
      between AD and VaD cases neither in men (P=0.315) nor women (P=0.12). Thus, we
      could not confirm that the length of telomeres would predict which form of
      dementia, late-onset AD or VaD that develops.

PMID- 18628665
TI  - Olig1 is downregulated in oligodendrocyte progenitor cell differentiation.
AB  - Olig1 is a transcription factor that is essential for oligodendrogenesis. It is
      important to understand the upstream regulation of Olig1 expression because of
      its critical role in remyelination repair. A mouse oligodendrocyte progenitor
      cell (OPC) differentiation model was established to explore Olig1 transcriptional
      activity during OPC differentiation. Using an Olig1 promoter-luciferase reporter
      plasmid, we found that Olig1 transcription is dramatically decreased during OPC
      differentiation in response to 0.5% fetal bovine serum. Olig1 protein expression
      is also remarkably decreased as revealed by immunostaining and western blotting.
      Thus, Olig1 is downregulated during OPC differentiation, suggesting that Olig1 is
      not actively required in differentiated oligodendrocytes.

PMID- 18628666
TI  - Enhancement of glutamate uptake in 1-methyl-4-phenylpyridinium-treated astrocytes
      by trichostatin A.
AB  - Histone deacetylases (HDAC) inhibitors have been emerging as neuroprotective
      agents by acting on neurons and microglia. In this study, we found trichostatin A
      (TSA), a HDAC inhibitor, could inhibit the elevation of glutamate in 150 microM 1
      methyl-4-phenylpyridinium (MPP+)-treated primary cultured astrocytes medium when
      its concentration reached 132 nM. TSA of 132 nM or more could promote the uptake
      of [3H]-D, L-glutamate by astrocytes. Further study showed the downregulation of
      glutamate transporter 1 and glutamate/aspartate transporter induced by MPP+ were
      prevented by TSA. Therefore, these findings suggested TSA could alleviate MPP+
      induced impairment of astrocytic glutamate uptake, which might be a novel
      mechanism contributing to neuroprotection by HDAC inhibitors.

PMID- 18628667
TI  - Postsynaptically different inhibitory postsynaptic currents in Cajal-Retzius
      cells in the developing neocortex.
AB  - Fast and slowly rising inhibitory postsynaptic currents (IPSCs, IPSCF and IPSCS)
      in neocortical Cajal-Retzius cells are observed. In this study, zolpidem, a
      benzodiazepine agonist that specifically modulates gamma-aminobutyric acid type A
      receptors (GABAARs) containing gamma2 subunit, was used to characterize GABAARs
      mediating IPSCF and IPSCS. One-hundred-nanomolar zolpidem prolonged IPSCS,
      increased evoked IPSCS (eIPSCS) amplitude, and decreased paired-pulse ratio (PPR)
      of eIPSCS. Two micromolar zolpidem prolonged both IPSCF and IPSCS, increased
      miniature IPSCF and eIPSCF amplitudes, increased eIPSCS amplitude but not
      miniature IPSCS amplitude, decreased PPR of eIPSCS, but failed to affect PPR of
      eIPSCF. We conclude that IPSCF are mediated by alpha2/3-containing GABAARs, which
      are not saturated by synaptic GABA release, whereas IPSCS are mediated by alpha1
      containing and alpha2/3-containing GABAARs, which are saturated by quantal GABA
      release.

PMID- 18628668
TI  - Human smooth pursuit gain is modulated by a signal related to gaze velocity.
AB  - The gain in smooth pursuit eye movements in primates depends on the ongoing
      pursuit velocity. To address the question of whether eye or gaze (equal to eye
      and head) velocity is the relevant signal that controls gain, patients were
      instructed to pursue a continuously moving target with (headfree) and without
      (headfixed) the use of head movements. Eye velocity differed significantly
      between the head-fixed and headfree conditions. To estimate the gain, the
      response to a brief perturbation of the target velocity was measured. Analysis of
      variance revealed that the target ([almost equal to]gaze) velocity had a
      significant and equal influence in both headfixed and headfree conditions. This
      finding indicates that gaze velocity modulates the response.

PMID- 18628669
TI  - Event-related potentials during preattentional processing of color stimuli.
AB  - To investigate whether visual mismatch negativity (VMMN) could be evoked in the
      preattentional condition, we designed an oddball task with different red color
      stimuli in visual modality. Electroencephalograms were recorded and VMMN and N2
      P3 complex waveforms were analyzed. The results indicated that VMMN generated at
      occipital region with 110-180 ms peak latency, and N2b and P3a were just
      following VMMN with 170-300 and 400-450 ms latencies, respectively. VMMN, N2b,
      and P3a components were all affected by the amount of deviations between the
      standard stimuli and deviant stimuli. This study further proved that VMMN existed
      under hard detection condition in color-related visual modality, and this design
      distinguished early sensory processing and late sensory processing successfully
      as well.

PMID- 18628670
TI  - Interference and facilitation in overt speech production investigated with event
      related potentials.
AB  - We report an event-related potential study investigating the neural basis of
      interference and facilitation in the picture-word interference paradigm with
      immediate overt naming. We used the high temporal resolution of the
      electrophysiological response to dissociate general and specific interference
      processes, by comparing unrelated word distractors to nonlinguistic (a row of
      Xs), surface feature denoting, and category member distractors. Our results first
      indicate that the increased naming latencies for linguistic relative to
      nonlinguistic distractors are because of general conflict-monitoring processes,
      associated with early event-related potential effects (120-220 ms) and increased
      activity in the anterior cingulate cortex. Next, distractors specifying a surface
      feature of the picture seem to facilitate its identification within the same time
      window, which involves widespread networks. Finally, nonlinguistic and surface
      feature distractors also reduced the N400 amplitude, relative to unrelated word
      distractors. Taken together our results support the view that several distinct
      processes give rise to the reaction time results often observed in picture
      naming.

PMID- 18628671
TI  - The right hemisphere fails to orient to the negative valence of visually
      presented words.
AB  - To assess cerebral functional asymmetry for accessing the meaning of emotional
      words, native English speakers were asked to make lexical decisions to emotional
      words, neutral words and nonwords briefly flashed in their left or right visual
      field, that is, perceived by their right or left visual cortex, respectively.
      Emotionally negative words had an overall probability of occurrence of 12.5% in
      each visual field and were expected to elicit a P3b event-related potential
      modulation indexing shifts of attention. Emotionally negative words elicited a
      P3b when perceived by the left visual cortex but failed to trigger such attention
      related response when perceived by the right hemisphere. The results suggest
      relative insensitivity on the part of the right hemisphere in registering the
      negative emotional valence of written words.

PMID- 18628672
TI  - Ketogenic diet does not disturb neurogenesis in the dentate gyrus in rats.
AB  - The ketogenic diet, a high-fat diet, is a therapeutic alternative in the
      treatment of refractory epilepsy, especially in children. However, there are
      concerns that a high-fat diet may influence the normal development of the central
      nervous system and cognition. In this study we investigated the influence of
      ketogenic diet on adult neurogenesis in the dentate gyrus. Rats were provided
      with either a high-fat diet (80% fat) or a standard rat diet (5% fat) ad libitum
      for 4 weeks. In both female and male rats, the amounts of bromodeoxyuridine
      immunoreactive cells in the dentate gyrus were the same in the different groups.
      Our results suggest that the ketogenic diet does not disturb the neurogenesis in
      the rat dentate gyrus.

PMID- 18628673
TI  - The key enzyme of sialic acid biosynthesis (GNE) promotes neurite outgrowth of
      PC12 cells.
AB  - Axonal outgrowth is a prerequisite for the development of the most complex organ,
      the brain. It depends partially on the attachment of sialic acid on glycans of
      (sialo)-glycoproteins expressed on the plasma membrane. In our study, we showed
      that nerve growth factor-induced neurite outgrowth of PC12-cells enhances the
      expression of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase
      (GNE), the key enzyme for the biosynthesis of sialic acid. Furthermore, we could
      show that overexpression of GNE induces neurite outgrowth in PC12 cells. The
      neurite-outgrowth promoting activity of overexpressed GNE, however, does not lead
      to an increased biosynthesis of sialic acid. These data suggest a novel role of
      GNE during neurite outgrowth, which is independent to its specific enzymatic
      activity.

PMID- 18628674
TI  - Effects of escapable and inescapable stressors on behavior and interleukin-2 in
      the brain.
AB  - This study aimed to clarify the effects of inescapable and escapable stressors on
      behavior and interleukin-2 (IL-2) levels in the brain. Inescapable trials,
      consisting of pairings of conditioned and unconditioned stimuli, were used to
      induce fear-conditioned stress, whereas trials of escapable pairings of
      conditioned and unconditioned stimuli in an active avoidance test were used as
      acute and conditioned stressors. IL-2 levels in the brain were analyzed by enzyme
      linked immunoadsorbent assays. Inescapable and escapable stressors had different
      effects on behavior in the modified active avoidance test and on IL-2 levels in
      brain areas that are known to be involved in emotional processes. These data
      provide insight into the pathophysiological role of IL-2 in stress-related
      disorders.

PMID- 18628675
TI  - Evidence of depressive symptoms in fragile-X syndrome premutated females.
AB  - OBJECTIVES: Fragile-X premutation carriers have been considered asymptomatic
      patients for a long time. It has been, however, demonstrated that the premutation
      is also involved in clinical pathology, such as premature ovarian failure, the
      fragile-X-associated tremor/ataxia syndrome, and a distinct neurocognitive and
      behavioral phenotype, which includes psychiatric problems. To define better this
      neuropsychiatric phenotype associated with premutation carriers and to minimize a
      possible environmental effect, we examined psychiatric and depressive symptoms in
      34 FMR1 premutation carrier mothers of children with fragile-X syndrome in
      comparison with two control groups (39 mothers with a non-fragile-X syndrome
      mentally retarded child and 39 mothers from the general population). METHODS: All
      participants completed both questionnaires, which assess psychiatric symptoms
      (the symptom checklist-90-revised) and depression (Beck Depression Inventory).
      RESULTS: Both groups of mothers with a mentally retarded child showed greater
      susceptibility to psychological problems than the control group without a
      mentally retarded child, but FMR1 premutated mothers evidenced a higher tendency
      to depression. These results suggest that, despite the stress of caring for a
      child with mental retardation, the premutation by itself could be responsible for
      some psychiatric traits. CONCLUSION: Our findings reinforce the hypothesis of a
      pathogenic gene-brain-behavior mechanism in the premutation range.

PMID- 18628676
TI  - Genome screen of 15 Australian bipolar affective disorder pedigrees supports
      previously identified loci for bipolar susceptibility genes.
AB  - OBJECTIVE: Despite many studies into the genetics of bipolar disorder (BP), the
      molecular causes underlying susceptibility to BP remain unclear. The aim of this
      study was to identify chromosomal regions linked to BP in a new Australian
      extended pedigree cohort. METHODS: We have conducted a parametric genome-wide
      linkage scan on 15 previously unreported Australian extended families with BP and
      related affective disorders, comprising 63 affected and 158 nonaffected
      individuals. RESULTS: This study provides support for previously identified
      linkage regions on chromosomes 1p13-31, 3q24-25, 4q13-32, 10p11-q11, and 15q21
      23, although none of these regions reached suggestive or significant evidence for
      linkage. CONCLUSION: Although not providing statistically significant evidence
      for linkage in this study, these 15 families provide support for previously
      identified bipolar susceptibility loci, and may aid in localizing susceptibility
      genes for BP in a larger combined cohort framework.

PMID- 18628677
TI  - Angiotensinogen M235T polymorphism and symptoms of depression in a population
      based study and a family-based study.
AB  - BACKGROUND: Evidence suggests that the angiotensinogen (AGT) gene is involved in
      depression. The aim of this paper is to examine the association between the AGT
      M235T polymorphism and symptoms of depression in two independent populations; a
      population-based study, and a family-based study. METHODS: Symptoms of depression
      were scored using the Centre of Epidemiological Studies Depression Scale (CES-D)
      and compared between the MM, MT, and TT genotype groups. The extent to which AGT
      M235T explains the heritability of the scores was examined using a variance
      components analysis. RESULTS: A significant relationship between the AGT M235T
      polymorphism and CES-D scores was found in men in both populations. The
      heritability estimate was 32%. The AGT genotype contributed to 1% of the total
      variance of the CES-D scores. CONCLUSION: Our findings suggest that the AGT gene
      is involved in the aetiology of symptoms of depression in men.

PMID- 18628678
TI  - Polymorphisms of the serotonin transporter gene (5-HTTLPR, A/G SNP in 5-HTTLPR,
      and STin2 VNTR) and their relation to personality traits in healthy individuals
      from Russia.
AB  - OBJECTIVE: Numerous studies have reported association of the serotonin
      transporter gene (5-HTT) polymorphisms and neuroticism and traits characterizing
      sociability and activity. This study aimed to define a single genotype effect of
      three polymorphic markers in the 5-HTT gene (5-HTTLPR, A/G SNP in 5-HTTLPR and
      STin2 VNTR) and to check possible association of the 5-HTT haplotypes and
      personality traits [assessed with Eysenck Personality Inventory (EPI) and
      Temperament and Character Inventory (TCI) questionnaires] in 301 healthy young
      individuals. METHODS: To investigate single genotype and haplotype effects of all
      polymorphic markers, multivariate analysis of variance and haplotype trend
      regression analyses were conducted correspondingly. RESULTS: Individuals with
      STin2.10 allele scored significantly lower on Neuroticism (EPI) (P=0.007) and
      Harm Avoidance (P=0.005) in the overall sample. The same pattern of association
      was reported in women: carriers of STin2.10 allele scored lower on Harm Avoidance
      (TCI) (P=0.008). Haplotype trend regression analyses revealed that carriers of
      S12 haplotype had lower sociability-related traits such as Extraversion (EPI) and
      Novelty Seeking (TCI), whereas Harm Avoidance (TCI) (anxiety-related trait) was
      higher. Opposite association was observed for S10 haplotype: Extraversion (EPI)
      score was higher, whereas Harm Avoidance (TCI) score was lower in carriers of
      this haplotype. CONCLUSION: As single polymorphism effect of STin2 was observed
      in relation to anxiety-related traits, opposite S10 and S12 haplotype effects on
      Neuroticism and Harm Avoidance could be explained by the larger impact of STin2
      polymorphism. Controversially, we consider that the variance in sociability
      related traits is related to specific haplotypes of 5-HTT gene.

PMID- 18628679
TI  - Brain-derived neurotrophic factor polymorphisms and frontal cortex morphology in
      schizophrenia.
AB  - OBJECTIVE: To investigate associations between brain-derived neurotrophic factor
      (BDNF) gene polymorphisms and regional frontal cortical thickness and volume in
      patients with schizophrenia and healthy control participants. METHODS: BDNF
      genotyping was performed using polymerase chain reaction and pyrosequencing
      techniques in 96 patients with schizophrenia or schizoaffective disorder and 104
      healthy control participants. Cortical morphology was analyzed by processing
      magnetic resonance brain images with the FreeSurfer software package. General
      linear model analysis was used to study associations between BDNF variants and
      cortical thickness in patients and controls, respectively. Regional frontal
      cortical volumes were defined from automatic cortical parcellations. RESULTS: For
      patients with schizophrenia, there was an association between the BDNF -633 T/A
      polymorphism and thickness and volume of distinct subregions of the prefrontal
      cortex. Data indicated trends toward genotypic associations between the BDNF 270
      C/T and 11757 G/C polymorphisms and the volume of specific frontal lobe regions
      in patients with schizophrenia. Among controls, there were no significant
      associations between BDNF polymorphisms and cortical thickness. Trends toward
      genotypic associations between BDNF polymorphisms and volumes of some frontal
      lobe regions for control participants were observed, although these differences
      did not reach statistical significance. CONCLUSION: Polymorphisms in the BDNF
      gene may be associated with variation in frontal lobe morphology. Associations
      seem to be stronger in patients with schizophrenia than in healthy controls.

PMID- 18628680
TI  - The influence of 5-HTTLPR and STin2 polymorphisms in the serotonin transporter
      gene on treatment effect of selective serotonin reuptake inhibitors in depressive
      patients.
AB  - BACKGROUND: Serotonin transporter gene (SLC6A4) variations have been proposed as
      an explanation for interindividual differences in selective serotonin reuptake
      inhibitors (SSRIs) effects. Quantitative assessment of genetic influences is
      necessary to evaluate whether genetic testing before antidepressant prescription
      would lead to earlier treatment effects. This study evaluates the influence of
      two polymorphisms (5-HTTLPR and STin2) on SSRI treatment outcome in depression.
      METHODS: We included 50 SSRI nonresponders (cases) and 164 referents meeting
      Diagnostic and Statistical Manual Of Mental Disorder-IV criteria for major
      depression and using an SSRI for at least 6 weeks. Blood samples or buccal swabs
      were gathered to determine 5-HTTLPR (N=48 for cases and 161 for referents) and
      STin2 (N=50 for cases and 162 for referents) genotypes. The association between
      genotype and SSRI response was assessed by use of logistic regression. RESULTS:
      Patients with the 5-HTTLPR s-allele had a nonsignificantly increased risk of SSRI
      nonresponse; odds ratio (OR) 1.60, 95% confidence interval (CI) 0.66-3.89. 5
      HTTLPR effects were strongest in female patients (OR 3.54, 95% CI 1.05-11.92),
      and for male patients 5-HTTLPR seemed to have no effect (OR 0.29, 95% CI 0.04
      2.34). An age-dependent effect of 5-HTTLPR was observed; patients under 44 years
      of age had an increased nonresponse risk (OR 9.34, 95% CI 1.41-61.98). STin2
      genotype had no clear influence on treatment outcome. CONCLUSION: Our findings
      indicate that women with the 5-HTTLPR s-allele have a less favorable response to
      SSRI treatment. To our knowledge, this is the first time that a gender-dependent
      influence of 5-HTTLPR is reported. More research is needed, particularly in
      subgroups of patients, before implementation of genetic testing can be
      recommended.

PMID- 18628681
TI  - Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest
      susceptibility loci at chromosomes 16 and 20.
AB  - OBJECTIVE: Our aim is to map chromosomal regions that harbor loci that increase
      susceptibility to bipolar disorder. METHODS: We analyzed 644 bipolar families
      ascertained by the National Institute of Mental Health Human Genetics Initiative
      for bipolar disorder. The families have been genotyped with microsatellite loci
      spaced every approximately 10 cM or less across the genome. Earlier analyses of
      these pedigrees have been limited to nonparametric (model-free) methods and thus,
      information from unaffected subjects with genotypes was not considered. In this
      study, we used parametric analyses assuming dominant and recessive transmission
      and specifying a maximum penetrance of 70%, so that information from unaffecteds
      could be weighed in the linkage analyses. As in previous linkage analyses of
      these pedigrees, we analyzed three diagnostic categories: model 1 included only
      bipolar I and schizoaffective, bipolar cases (1565 patients of whom approximately
      4% were schizoaffective, bipolar); model 2 included all individuals in model 1
      plus bipolar II patients (1764 total individuals); and model 3 included all
      individuals in model 2 with the addition of patients with recurrent major
      depressive disorder (2046 total persons). RESULTS: Assuming dominant inheritance
      the highest genome-wide pair-wise logarithm of the odds (LOD) score was 3.2 with
      D16S749 using model 2 patients. Multipoint analyses of this region yielded a
      maximum LOD score of 4.91. Under recessive transmission a number of chromosome 20
      markers were positive and multipoint analyses of the area gave a maximum LOD of
      3.0 with model 2 cases. CONCLUSION: The chromosome 16p and 20 regions have been
      implicated by some studies and the data reported herein provide additional
      suggestive evidence of bipolar susceptibility genes in these regions.

PMID- 18628682
TI  - Association study between genetic variants at the VAMP2 and VAMP3 loci and
      bipolar affective disorder.
AB  - OBJECTIVES: Vesicle-associated membrane proteins 2 and 3 (VAMP2 and VAMP3) are
      required for the release of D-serine, a competitive agonist of the
      neurotransmitter glycine at the glutamatergic N-methyl-D-aspartate receptors.
      Several lines of evidence point to an involvement of altered D-serine levels in
      the central nervous system in the aetiology of bipolar affective disorder (BPAD).
      Strong association findings between BPAD and two genes, G72 and DAAO, which are
      involved in the enzymatic degradation of D-serine, are reported. Based on the
      functional evidence and on the hypothesis that further genes, which are involved
      in the regulation of D-serine, could be involved in the disease aetiology, we
      considered VAMP2 and VAMP3 as candidate genes for BPAD. METHODS: We analyzed
      three and four single nucleotide polymorphism (SNP) markers covering VAMP2 and
      VAMP3, respectively, in an initial BPAD case-control sample of German descent
      (409 cases, 407 controls). For replication, we analyzed three SNP markers
      covering VAMP2 in a second sample of the same ethnicity (378 cases, 384
      controls). RESULTS: Although no association was found for VAMP3 markers, we
      observed evidence of association with SNPs at the VAMP2 locus in the initial
      sample (P values between 0.005 and 0.033). To validate these findings, we
      analyzed a second BPAD sample and failed to replicate the initial findings at the
      single-marker and haplotypic level. CONCLUSION: In conclusion, our results do not
      suggest that a common genetic variant at VAMP2 or VAMP3 contributes to the
      development of BPAD in German patients.

PMID- 18628683
TI  - Analysis of the neuroligin 4Y gene in patients with autism.
AB  - Frameshift and missense mutations in the X-linked neuroligin 4 (NLGN4, MIM#
      300427) and neuroligin 3 (NLGN3, MIM# 300336) genes have been identified in
      patients with autism, Asperger syndrome and mental retardation. We hypothesize
      that sequence variants in NLGN4Y are associated with autism or mental
      retardation. The coding sequences and splice junctions of the NLGN4Y gene were
      analyzed in 335 male samples (290 with autism and 45 with mental retardation). A
      total of 1.1 Mb of genomic DNA was sequenced. One missense variant, p.I679V, was
      identified in a patient with autism, as well as his father with learning
      disabilities. The I679 residue is highly conserved in three members of the
      neuroligin family. The absence of p.I679V in 2986 control Y chromosomes and the
      high similarity of NLGN4 and NLGN4Y are consistent with the hypothesis that
      p.I679V contributes to the etiology of autism. The presence of only one
      structural variant in our population of 335 males with autism/mental retardation,
      the unavailability of significant family cosegregation and an absence of
      functional assays are, however, important limitations of this study.

PMID- 18628684
TI  - No support for an association with TAAR6 and schizophrenia in a linked population
      of European ancestry.
AB  - Single nucleotide polymorphisms (SNPs) in the trace amine associated receptor
      trace amine associated receptor 6 gene and 3' flanking region have been shown to
      be associated with schizophrenia. To replicate these findings, we conducted a
      family-based association study with the five most significant SNPs in our sample
      of 79 sib-pair families (56/79 sib-pair families showed linkage to 6q23) and 125
      triads. No evidence for association was obtained between these SNPs and
      schizophrenia in our sample, even when limited to the 56 linked families (P>0.2).
      We conclude that trace amine associated receptor 6 is not important for the
      development of schizophrenia in our family samples.

PMID- 18628685
TI  - GSTz1 genotype and cognitive ability.

PMID- 18628686
TI  - What's new in Shock, August 2008?

PMID- 18628687
TI  - Effect of cyclopentanone prostaglandin 15-deoxy-delta12,14PGJ2 on early
      functional recovery from experimental spinal cord injury.
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma is a member of the
      nuclear-receptor superfamily that binds to DNA with retinoid X receptors as PPAR
      retinoid X receptor heterodimers. Recent evidence also suggests that the
      cyclopentenone prostaglandin 15-deoxy-DeltaPGJ2 (15d-PGJ2), which is a metabolite
      of the prostaglandin D2, functions as an endogenous ligand for PPAR-gamma We
      postulated that 15d-PGJ2 would attenuate inflammation, investigating the effects
      on the degree of experimental spinal cord trauma induced by the application of
      vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy.
      Spinal cord injury in mice resulted in severe trauma characterized by edema,
      neutrophil infiltration, production of a range of inflammatory mediators, tissue
      damage, and apoptosis. Furthermore, 15d-PGJ2 reduced (1) spinal cord inflammation
      and tissue injury (histological score), (2) neutrophil infiltration
      (myeloperoxidase activity), (3) nuclear factor-kappaB activation, (4) expression
      of iNOS, nitrotyrosine and TNF-alpha, and (5) apoptosis (terminal
      deoxynucleotidyltransferase-mediated uridine triphosphate end labeling staining,
      Bax, Bcl-2, and FAS-L expression). In a separate set of experiments, 15d-PGJ2
      significantly ameliorated the recovery of limb function (evaluated by motor
      recovery score). To elucidate whether the protective effects of 15d-PGJ2 are
      related to activation of the PPAR-gamma receptor, we also investigated the effect
      of a PPAR-gamma antagonist, GW 9662, on the protective effects of 15d-PGJ2.
      GW9662 (1 mg/kg administered i.p. 30 min before treatment with 15d-PGJ2)
      significantly antagonized the effect of the PPAR-gamma agonist and, thus,
      abolished the protective effect. Taken together, our results clearly demonstrate
      that treatment with 15d-PGJ2 reduces the development of inflammation and tissue
      injury associated with spinal cord trauma.

PMID- 18628688
TI  - Activated protein C attenuates leukocyte elastase-induced lung injury in mice.
AB  - Leukocyte elastase (LE), a neutrophil serine protease, is known to cause alveolar
      wall destruction and alveolar hemorrhage in the lung, but recent evidence
      suggests that it may also produce a significant inflammatory response. The
      purpose of the current study was to (1) examine the relationship between LE
      induced lung injury and specific markers of inflammation and cytokine/chemokine,
      and to (2) determine the potential of activated protein C (APC), a potent
      immunomodulator, to block the inflammatory response to LE. We treated the C57BL/6
      mice with LE (10 U/kg, i.t.) and assessed the lung inflammation over 72 h. Total
      cells, total protein, and neutrophils were increased and peaked at 16 h in
      bronchial alveolar lavage fluid. Macrophages were also increased and peaked at 24
      h. Administration of LE up-regulated the synthesis of proinflammatory cytokines,
      IL-1beta and IL-6, chemokines, keratinocyte-derived chemokine, and macrophage
      inflammatory protein 2 in bronchial alveolar lavage fluid, and their peaks were
      at 6 h. Furthermore, the mice were treated with APC at 0.2, 2.0, and 10 mg/kg
      (i.v.) after instillation of LE. Therapeutic treatment of APC at 2.0 and 10 mg/kg
      significantly attenuated the increases in all these parameters. Lung histology
      revealed that, in addition to inflammation, alveolar hemorrhage and alveolar wall
      destruction induced by LE were also attenuated by APC. Finally, the expression of
      tissue plasminogen activator and plasminogen activator inhibitor in whole lung of
      mice exposed to LE, detected by means of reverse-transcriptase-polymerase chain
      reaction, were not influenced by the treatment with APC. These data demonstrate
      that intratracheal administration of LE to mice causes a transient inflammatory
      response, and APC can play a protective role against LE-induced lung injury.

PMID- 18628689
TI  - A peptide inhibitor of C-jun N-terminal kinase modulates hepatic damage and the
      inflammatory response after hemorrhagic shock and resuscitation.
AB  - Hemorrhage and resuscitation (H/R) leads to phosphorylation of mitogen-activated
      stress kinases, an event that is associated with organ damage. Recently, a
      specific, cell-penetrating, protease-resistant inhibitory peptide of the mitogen
      activated protein kinase c-JUN N-terminal kinase (JNK) was developed (D-JNKI-1).
      Here, using this peptide, we tested if inhibition of JNK protects against organ
      damage after H/R. Male Sprague-Dawley rats were treated with D-JNKI-1 (11 mg/kg,
      i.p.) or vehicle. Thirty minutes later, rats were hemorrhaged for 1 h to a MAP of
      30 to 35 mmHg and then resuscitated with 60% of the shed blood and twice the shed
      blood volume as Ringer lactate. Tissues were harvested 2 h later. ANOVA with
      Tukey post hoc analysis or Kruskal-Wallis ANOVA on ranks, P < 0.05, was
      considered significant. c-JUN N-terminal kinase inhibition decreased serum
      alanine aminotransferase activity as a marker of liver injury by 70%, serum
      creatine kinase activity by 67%, and serum lactate dehydrogenase activity by 60%
      as compared with vehicle treatment. The histological tissue damage observed was
      blunted after D-JNKI-1 pretreatment both for necrotic and apoptotic cell death.
      Hepatic leukocyte infiltration and serum IL-6 levels were largely diminished
      after D-JNKI-1 pretreatment. The extent of oxidative stress as evaluated by
      immunohistochemical detection of 4-hydroxynonenal was largely abrogated after JNK
      inhibition. After JNK inhibition, activation of cJUN after H/R was also reduced.
      Hemorrhage and resuscitation induces a systemic inflammatory response and leads
      to end-organ damage. These changes are mediated, at least in part, by JNK.
      Therefore, JNK inhibition deserves further evaluation as a potential treatment
      option in patients after resuscitated blood loss.

PMID- 18628691
TI  - Re: Increased levels of serum S100B protein in critically ill patients without
      brain injury.

PMID- 18628692
TI  - Simvastatin stimulates chondrogenic phenotype of intervertebral disc cells
      partially through BMP-2 pathway.
AB  - STUDY DESIGN: In vitro experiment to study the effect of simvastatin on rat
      intervertebral disc (IVD) cells. OBJECTIVE: To evaluate the time-course effect of
      simvastatin on the gene expression of bone morphogenetic protein-2 (BMP-2),
      aggrecan, and collagen type II in rat IVD cells cultured in alginate bead. Role
      of BMP-2 on the simvastatin-induced chondrogenesis of IVD cells was also
      investigated. SUMMARY OF BACKGROUND DATA: Growth factors including BMP-2 have
      been found to improve anabolism of IVD cells and have shown promise for the
      treatment of disc degeneration. Statins is known to increase BMP-2 expression in
      vitro and stimulate bone formation in vivo. However, it is still unknown whether
      statins can also increase BMP-2 expression and in turn, stimulate matrix
      synthesis by IVD cells. METHODS: Rat IVD cells (harvested from nucleus pulpusos
      and inner annular fibrosus) cultured in alginate beads were exposed to different
      doses of simvastatin. DMMB, and real-time polymerase chain reaction were used to
      quantify proteoglycan and gene expression of BMP-2, aggrecan and collagen type
      II, respectively. Noggin or mevalonate was used to investigate the mechanism of
      the effect of simvastatin on rat IVD cells. RESULTS: Simvastatin significantly
      upregulated BMP-2 mRNA expression, followed by aggrecan and type II collagen gene
      expression and proteoglycan content in rat IVD cells. Moderate dose (500 ng/mL)
      of noggin completely hindered the expression of aggrecan and collagen type II
      induced by simvastatin on day 7, but not on day 14. The upregulated type II
      collagen expression was blocked with 3 mug/mL of noggin on day 14, whereas
      aggrecan levels remained unchanged. Lastly, simvastatin appeared to facilitate
      BMP-2, aggrecan, and type II collagen gene expression by inhibiting the
      production of mevalonate as evidenced that the anabolic effect was completely
      reversed with the addition of mevalonate. CONCLUSION: Simvastatin drives a
      mechanism for promoting chondrogenesis of IVD cells partially mediated by
      upregulated BMP-2 through the inhibition of mevalonate pathway.

PMID- 18628693
TI  - Motor control learning in chronic low back pain.
AB  - STUDY DESIGN: A randomized prospective cohort study of participants with chronic
      low back pain, seeking physical therapy, with follow-up at weeks 6 and 28.
      Effects of conventional physiotherapy and physiotherapy with the addition of
      postural biofeedback were compared. OBJECTIVE: To evaluate the benefits of
      postural biofeedback in chronic low back pain participants. SUMMARY OF BACKGROUND
      DATA: Biofeedback using electromyographic signals has been used in chronic low
      back pain with mixed results. Postural feedback had not been previously used.
      METHODS: Demographic and psychological baseline data along with range of motion
      were analyzed from a sample of 47 chronic participants with low back pain
      randomized into conventional physiotherapy with or without the addition of
      postural biofeedback. RESULTS: After 6 months, there were 21 dropouts. The
      participants with biofeedback had markedly improved status in visual analog pain
      scales, short form-36, and range of motion. CONCLUSION: The study strongly
      suggests that postural feedback is a useful adjunct to conventional physiotherapy
      of chronic low back pain participants.

PMID- 18628694
TI  - Consciously postural sway and cervical vertigo after whiplash injury.
AB  - STUDY DESIGN: Cross-sectional study of whiplash injury patients with vertigo and
      healthy volunteers consciously pretending to have postural sway as in
      malingering. OBJECTIVE: The aim of this study was to evaluate the postural sway
      in malingerers by posturography. SUMMARY OF BACKGROUND DATA: Malingering is not a
      problem in the majority of cases with whiplash injury and diagnosis should be
      made carefully. However, some patients with whiplash injury might exaggerate
      their symptoms or be malingerers because of the potential gain associated with
      insurance claims. We designed a diagnostic study to screen putative malingerers.
      METHODS: Subjects were 20 healthy volunteers who were tested under standing
      condition (normal group), consciously swaying the body under standing condition
      like malingerers (pseudomalingering group) and 32 patients who complained of neck
      pain with vertigo or dizziness after whiplash injury with WAD (whiplash
      associated disorders) grade I and II (WAD group). The movement of the center of
      pressure (COP) was measured using a force platform to quantify postural sway.
      Static posturography was performed under open and closed eyes. We analyzed (1)
      total envelop area per unit of time (EAREA), (2) shifting length per second
      (LNG/TIME), (3) sway pattern, and (4) Romberg rate representing total shifting
      length under eyes-closed/eyes-open. RESULTS: In open eyes condition, the values
      of EAREA and LNG/TIME were significant higher under pseudomalingering than both
      of the control and WAD groups (P < 0.05). The Romberg rate was 1.30 +/- 0.17,
      1.13 +/- 0.19, and 1.83 +/- 0.94 in control, pseudo-malingering, and WAD group,
      respectively, and was less than 1.0 in 45% of pseudomalingering. There were
      significant differences in the EAREA, LEN/TIME, and Romberg rate between
      pseudomalingering and the other 2 groups (P < 0.05). CONCLUSION: Our results
      suggest that compared with normal subjects and WAD patients, malingerers are more
      likely to exhibit a wide EAREA, a long sway length per second, and a low Romberg
      rate. Malingering must be diagnosed carefully and posturography could be a
      helpful supplementary tool for differentiating whiplash-associated vertigo from
      malingering.

PMID- 18628695
TI  - Effect of fibrin sealant on drain output and duration of hospitalization after
      multilevel anterior cervical fusion: a retrospective matched pair analysis.
AB  - STUDY DESIGN: Retrospective matched pair analysis. OBJECTIVE: To determine if
      fibrin sealant can decrease postoperative drain output and length of stay (LOS)
      after multilevel anterior cervical fusions. SUMMARY OF BACKGROUND DATA: Despite
      careful hemostasis, bleeding after anterior cervical fusion can occur and may be
      life threatening. Although fibrin sealants are commonly used for hemostasis, no
      studies have been published on the efficacy of these products in achieving
      hemostasis after anterior cervical surgery. METHODS: A retrospective age-, gender
      , and fusion level-matched pair analysis was performed on 30 pairs of patients
      who underwent anterior cervical fusion >or= 3 levels. In the study group, after
      adequate hemostasis was obtained, before wound closure 2.0 mL of fibrin sealant
      was applied as a fine aerosolized spray over and around the plate/fusion sites
      and the soft tissues to seal the main operative field. A deep drain was used in
      all patients. Total drain output, time for the drainage to decrease to <or=20 mL
      per 8 hours shift, LOS, and number of readmissions were determined and analyzed
      by experienced and independent spine surgeons. RESULTS: Total drain output
      averaged 47 mL in the study group and 98 mL in the control group (P < 0.0001).
      Time for the drainage to decrease to <or=20 mL per shift averaged 17 hours
      (range, 8-29 hours) in the study group and 24 hours (range, 7-43 hours) in the
      control group (P = 0.0054). LOS averaged 1.2 days (range, 1-4 days) in the study
      group and 2.1 day (range, 1-5 days) in the control group (P < 0.0001). Two
      patients were readmitted within 4 days of discharge in each group because of
      swallowing difficulty, dyspnea, or pneumonia (P = 1.000). There were no adverse
      reactions attributable to the fibrin sealant. CONCLUSION: Application of fibrin
      sealant at the end of multilevel anterior cervical fusion can significantly
      decrease postoperative drain output and LOS.

PMID- 18628696
TI  - Plain radiography versus computed tomography scans in the diagnosis and
      management of thoracolumbar burst fractures.
AB  - STUDY DESIGN: The role of plain radiography in the diagnosis and management of
      thoracolumbar burst fractures was evaluated when compared with computed
      tomography (CT) scans. OBJECTIVE: To determine the accuracy of plain radiography
      in detecting thoracolumbar burst fractures when CT scans were used as the gold
      standard, and to assess the impact of disagreement of the results between plain
      radiographs and CT scans on treatment plan. SUMMARY OF BACKGROUND DATA: There
      have been few studies comparing the value of plain radiography with that of CT
      scans in the diagnosis and management of thoracolumbar burst fractures. METHODS:
      Radiographs of 73 patients with a compression or burst fracture were reviewed
      independently by 3 residents and 3 spine surgeons. The results of CT scans were
      used as the gold standard to determine the accuracy of plain radiography for the
      diagnosis. More quantitative results of 57 patients with a burst fracture based
      on plain radiographs alone were compared with those after addition of CT scans.
      The disagreement between the results was analyzed, and the impact of disagreement
      on treatment plan was defined as the changes of load sharing score between <or=6
      and >or=7. RESULTS: The accuracy of plain radiography improved with the
      experience of observers. The results on the load sharing score agreed between
      plain radiographs alone and radiographs with CT scans only for 56%, indicating
      moderate agreement. The impact of disagreement on treatment plan was significant
      (P < 0.05). This disagreement was most contributed by the underestimation for
      vertebral body comminution based on plain radiographs. CONCLUSION: The accuracy
      of plain radiography is acceptable in the qualitative sense, and would improve
      with the experience of observers. However, plain radiography alone would not be
      adequate when used for more quantitatively assessing the fractures. Addition of
      CT scanning is necessary for treatment planning.

PMID- 18628697
TI  - FokI variant of vitamin D receptor gene and factors related to atherosclerosis
      associated with ossification of the posterior longitudinal ligament of the spine:
      a multi-hospital case-control study.
AB  - STUDY DESIGN: A sex- and age-matched case-control study with genotyping of the
      FokI variant of the vitamin D receptor gene (VDR) was carried out. OBJECTIVES: To
      facilitate the early prediction, prevention, and treatment of ossification of the
      posterior longitudinal ligament (OPLL) of the spine, we analyzed the FokI variant
      of VDR and past body mass indexes, histories of past illness, family history, and
      body pliability along with lifestyle factors. SUMMARY OF BACKGROUND DATA: Many
      possible genetic and environmental risk factors for OPLL have been suggested,
      including male sex, high body mass index, diabetes mellitus, trauma, hormonal
      imbalance, and dietary and sleeping habits and genetic variants. METHODS: Both a
      self-administered questionnaire and whole blood samples were obtained from 63
      patients with OPLL and 126 sex-, age-, and hospital-matched controls free of
      backbone diseases were randomly selected from hospital patients. VDR genotyping
      was carried out using PCR-RFLP methods. After univariate analysis, multivariate
      and subgroup analyses according to the VDR genotype was applied to clarify the
      confounding relationship between VDR genotype and other possible risk factors.
      RESULTS: A multivariate analysis revealed that the VDR FF genotype, family
      history of myocardial infarction, high body mass index at age 40, long working
      hours, and working with night shift to be independent potent risk factors for
      OPLL. CONCLUSION: The risk of developing OPLL may possibly be reduced gradually
      and effectively by removing or minimizing the effect of such lifestyle factors
      one at a time through targeted preventive intervention.

PMID- 18628698
TI  - Surgical management of symptomatic cervical or cervicothoracic kyphosis due to
      ankylosing spondylitis.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: To evaluate surgical management and
      outcomes in the treatment of severe chin-on-chest deformities due to ankylosing
      spondylitis (AS). SUMMARY OF BACKGROUND DATA: AS is a chronic inflammatory
      disease that can lead to severe flexion deformities involving the cervicothoracic
      spine. The resulting chin-on-chest deformity can be extremely debilitating.
      METHODS: Literature search using PubMed database. RESULTS: Six retrospective
      clinical studies were identified. No randomized or prospective studies were
      found. The indication for surgery was primarily loss of horizontal gaze. The most
      common surgical technique was based on the original Simmons osteotomy at C7-T1.
      Analysis of radiographic studies and the chin-brow to vertical angles
      demonstrated significant improvement in the flexion deformity in all cases after
      surgery. The complication rate was high, ranging from 26.9% to 87.5%, with a
      mortality rate of 2.6%. However, most complications were minor, and the permanent
      neurologic complication rate was 4.3%. All patients had improvement in horizontal
      gaze, and patient satisfaction after surgery appeared high. CONCLUSION: Based on
      these studies, it seems that for the severely impaired patient with loss of
      horizontal gaze, surgical correction is a reasonable option with a high
      likelihood of success.

PMID- 18628699
TI  - Conservative management of perineural cysts.
AB  - STUDY DESIGN: A case series and literature review are presented. OBJECTIVE: To
      review relevant data for the management of perineural cysts, and present a case
      series of 2 patient with symptomatic perineural cysts treated by steroid therapy.
      SUMMARY OF BACKGROUND DATA: Perineural cysts are usually an incidental finding,
      but rarely may cause mechanical nerve root compression. Surgical treatments for
      perineural cysts are complicated by postoperative pseudomeningocoele and
      intracranial hypotension, and reoccurrence of the cyst. There are no reported
      nonsurgical treatments for perineural cysts. METHODS: We present a case series
      symptomatic perineural cysts. RESULTS: Patients with lumbar and cervical
      perineural cysts were treated successfully with oral and epidural steroid
      therapy. CONCLUSION: Steroid therapy may offer a nonsurgical alternative for the
      treatment of symptomatic perineural cysts.

PMID- 18628700
TI  - Ischemic orbital compartment syndrome after posterior spinal surgery.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a patient with ischemic orbital
      compartment syndrome after undergoing spinal surgery in a prone position. SUMMARY
      OF BACKGROUND DATA: Ocular complications after nonocular surgery are devastating.
      The most common etiology is ischemic optic neuropathy. Orbital compartment
      syndrome with ischemic change is quite rare and urgent management is necessary.
      METHODS: Early diagnosis and surgical intervention was performed for ischemic
      compartment syndrome after posterior spinal surgery was done. RESULTS: Despite
      immediate management, the patient remained blind and ptotic 3 months after the
      injury. CONCLUSION: Understanding ocular complications after spinal surgery is
      vital. Although rare, but the most troublesome complication is ischemic orbital
      compartment syndrome.

PMID- 18628701
TI  - Foot drop of sudden onset caused by acute hematoma in the lumbar ligamentum
      flavum: a case report and review of the literature.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To describe an unusual case of acute
      hematoma in the lumbar ligamentum flavum causing foot drop. SUMMARY OF BACKGROUND
      DATA: There have been several reports of hematoma in the lumbar ligamentum flavum
      causing compression of the cauda equina and/or nerve root. However, the majority
      of these cases were chronic hematomas, based on clinical history and histologic
      findings. METHODS: A 64-year-old man presented with right foot drop of sudden
      onset and severe sciatica. Magnetic resonance imaging (MRI) on the 10th day after
      the onset of symptoms revealed spinal stenosis at L4/5 caused by a posterior mass
      that was isointense on T1-weighted images and hyperintense on T2-weighted images,
      but was hyperintense on T1-weighted images and hypointense on T2-weighted images
      5 days later. Because of these neurologic findings, surgical exploration and
      excision of the intraspinal mass were performed on the 18th day after onset.
      RESULTS: Surgical treatment was uneventful, and the severe sciatica improved
      immediately after surgical treatment. Histologic examination revealed recent
      extravasation of blood in the degenerated ligamentum flavum. These findings were
      supported by the 2 consecutive preoperative MRI examinations. At 1 year after
      surgery, manual muscle testing of the tibialis anterior on the affected side had
      recovered to grade 4. CONCLUSION: Consecutive MRI examinations performed 5 days
      apart in the early stage after the onset of symptoms clearly demonstrated
      intensity change, indicating acute hematoma of ligamentum flavum as a cause of
      foot drop of sudden onset.

PMID- 18628703
TI  - Molecular changes in the degenerated goat intervertebral disc.
AB  - STUDY DESIGN: Caprine lumbar intervertebral discs (IVD) were collected from
      previous studies and categorized as normal, mildly, or severely degenerated. The
      biochemical composition and the RNA profiles present in both the nucleus pulposus
      (NP) and the anulus fibrosus (AF) were analyzed. OBJECTIVE: To determine the
      molecular changes occurring in a disc degeneration model, evaluating the
      mechanism through which the degeneration develops in this model. SUMMARY OF
      BACKGROUND DATA: Recently we described an IVD degeneration model in the goat by
      injecting chondroitinase ABC. This results in mild progressive disc degeneration.
      METHODS: One hundred nine caprine IVDs were assigned to 3 classes: no
      degeneration, mild, or severe degeneration. Collagen content, collagen cross
      links (hydroxylysyl pyridinoline) and the ratio between the glycosaminoglycans
      (GAGs) and hydroxyprolines (Hyp) (GAG/Hyp ratio) in the NP and AF samples were
      studied. Furthermore, the gene expression of collagen type I, type II, and
      aggrecan as well as a desintegrin and metalloproteinase with thrombospondin
      motifs (ADAMTIS)-2, ADAMTS-14, and matrix metalloproteinases-13 were studied.
      RESULTS: Collagen content was increased in severely degenerated NPs and decreased
      in severely degenerated AFs. Collagen cross-links were decreased in the severely
      degenerated NPs indicating de novo deposition of immature, reducible cross-linked
      collagens. The GAG/Hyp ratio found in none-degenerate goat discs was comparable
      to human ratios and decreased in degenerated discs, similar as in humans. The
      ADAMTS genes were increasingly detectable in the degenerated discs. The matrix
      metalloproteinases-13 gene increased significantly in degenerated discs. The
      expression of collagen type I increased in degenerated discs while aggrecan
      decreased. CONCLUSION: Changes in the GAG/Hyp ratio of chemically induced
      degeneration in goat IVD resemble the changes seen in humans. Gene expression
      profiles match the pattern of degeneration, suggesting that the injection of
      chondroitinase ABC might mimic the onset of human disc degeneration.

PMID- 18628704
TI  - Cement distribution, volume, and compliance in vertebroplasty: some answers from
      an anatomy-based nonlinear finite element study.
AB  - STUDY DESIGN: The biomechanics of vertebral bodies augmented with real
      distributions of cement were investigated using nonlinear finite element (FE)
      analysis. OBJECTIVES: To compare stiffness, strength, and stress transfer of
      augmented versus nonaugmented osteoporotic vertebral bodies under compressive
      loading. Specifically, to examine how cement distribution, volume, and compliance
      affect these biomechanical variables. SUMMARY OF BACKGROUND DATA: Previous FE
      studies suggested that vertebroplasty might alter vertebral stress transfer,
      leading to adjacent vertebral failure. However, no FE study so far accounted for
      real cement distributions and bone damage accumulation. METHODS: Twelve vertebral
      bodies scanned with high-resolution pQCT and tested in compression were augmented
      with various volumes of cements and scanned again. Nonaugmented and augmented
      pQCT datasets were converted to FE models, with bone properties modeled with an
      elastic, plastic and damage constitutive law that was previously calibrated for
      the nonaugmented models. The cement-bone composite was modeled with a rule of
      mixture. The nonaugmented and augmented FE models were subjected to compression
      and their stiffness, strength, and stress map calculated for different cement
      compliances. RESULTS: Cement distribution dominated the stiffening and
      strengthening effects of augmentation. Models with cement connecting either the
      superior or inferior endplate (S/I fillings) were only up to 2 times stiffer than
      the nonaugmented models with minimal strengthening, whereas those with cement
      connecting both endplates (S + I fillings) were 1 to 8 times stiffer and 1 to 12
      times stronger. Stress increases above and below the cement, which was higher for
      the S + I cases and was significantly reduced by increasing cement compliance.
      CONCLUSION: The developed FE approach, which accounts for real cement
      distributions and bone damage accumulation, provides a refined insight into the
      mechanics of augmented vertebral bodies. In particular, augmentation with
      compliant cement bridging both endplates would reduce stress transfer while
      providing sufficient strengthening.

PMID- 18628705
TI  - Frequency-dependent behavior of the intervertebral disc in response to each of
      six degree of freedom dynamic loading: solid phase and fluid phase contributions.
AB  - STUDY DESIGN: Nondestructive displacement-controlled dynamic testing of cadaver
      material, with repeated measures design and randomized sequence of tests.
      OBJECTIVE: To determine whether the frequency-dependent changes in disc stiffness
      and phase angle between load and displacement differ between the 6 principal
      directions of displacement, and whether these differences are greater in
      deformation directions associated with greater intradiscal fluid flow. SUMMARY OF
      BACKGROUND DATA: Prior studies of time-dependent behavior of discs have focused
      on compression. Comparing different deformation directions allows effects of
      fluid flow to be distinguished from effects of the solid phase viscoelasticity.
      METHODS: Vertebra-disc-vertebra preparations (N = 9) from human lumbar spines
      were subjected to each of 3 displacements and 3 rotations (6 degree of freedom)
      at each of 4 frequencies (0.001, 0.01, 0.1, and 1 Hz) after equilibration
      overnight under a 0.4 MPa preload in a bath of phosphate buffered saline at 37
      degrees C with protease inhibitors. The forces and torques were recorded along
      with the applied translation or rotation. The stiffness (force/displacement or
      torque/rotation) and the phase angle (between each force and displacement) were
      calculated for each degree of freedom from recorded data. RESULTS: Disc stiffness
      increased linearly with the log-frequency. The increases over the four decades of
      frequency were 35%, 33%, and 26% for AP shear, lateral shear, and torsion
      respectively, and were 45%, 29%, 51%, and 83% for compression, lateral bending,
      flexion, and extension. The phase angle (a measure of energy absorption) averaged
      6.2, 5.1, and 5.1 degrees in AP shear, lateral shear, and torsion, respectively,
      and 7.0, 7.0, and 8.6 degrees for compression, lateral bending, and flexion
      extension. There were no consistent variations of phase angle with frequency.
      CONCLUSION: The stiffness increase and phase angle decrease with frequency were
      greater for deformation modes in which fluid flow effects are thought to be
      greater.

PMID- 18628706
TI  - Significance of laminar screw fixation in the subaxial cervical spine.
AB  - STUDY DESIGN: We retrospectively reviewed 11 patients who underwent laminar screw
      fixation in the subaxial cervical spine. In 4 patients, laminar screws were
      inserted for posterior cervical arthrodesis, and in 7 patients it was used for
      fixation of the open laminae during laminoplasty. OBJECTIVE: In this study, the
      author describes the technique and surgical results of translaminar screw
      placement in the subaxial cervical spine. SUMMARY OF BACKGROUND DATA: The use of
      laminar screws for fixation of the second cervical vertebra and upper thoracic
      vertebrae has been introduced as an important technique in spinal surgery because
      they can avoid injury to adjacent neurovascular structures. However, there have
      been no reports of translaminar screw use in the subaxial spine including C7. In
      this study, we describe the use of translaminar screws for fixation of the
      subaxial cervical spine in cases of degenerative or traumatic spine disease.
      METHODS: Between June 2006 and March 2007, 34 translaminar screws were placed in
      11 patients to treat trauma or degenerative disease: 6 at C7, 6 at C6, 7 at C5, 7
      at C4, 7 at C3, and 1 at T1. There were 6 women and 5 men. The ages ranged from
      23 to 87 years with a mean age of 61.3 years. All patients were evaluated at 6
      weeks, as well as at 3 and 6 months using flexion and extension lateral
      radiographs. Patients requiring fusion were also evaluated with computed
      tomography at 3 and 6 months to verify arthrodesis. RESULTS: The mean follow-up
      period was 5.7 months, at which time there was no significant complications from
      laminar screw placement, except for 2 asymptomatic breaches of the dorsal lamina
      cortex. Sound bone fusion was identified in cases where arthrodesis was the goal.
      No screw pullout or avulsion was identified in the laminoplasty cases.
      CONCLUSION: The translaminar screw method avoided damaging vascular structures,
      especially when the vertebral artery courses in the C7 transverse foramen, and it
      maintains solid stabilization of the subaxial cervical spine. This technique has
      2 important advantages to currently used techniques: it is simpler and is not
      limited by the position of vascular structures. Therefore, it may be applicable
      to a wider number of patients, especially as it may be used in the subaxial
      cervical spine.

PMID- 18628707
TI  - Internal decapitation: survival after head to neck dissociation injuries.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To describe survival and outcomes after
      occipitocervical dissociation injuries. SUMMARY OF BACKGROUND DATA: Historically,
      occipitocervical dissociation injuries have a high rate of associated neurologic
      deficit with a relatively high incidence of mortality. METHODS: Six patients with
      occipitocervical dissociation injuries are reported and their management and
      imaging findings reviewed. Possible contributory factors for survival are
      discussed. RESULTS: All patients had upper neck and head dissociation injuries.
      The pattern of injury in all of these cases included a distraction type
      mechanism. All cases demonstrated soft tissue disruption in the zone of injury,
      which was consistent and apparent on all imaging studies. In these patients, the
      extent and severity of injury was more apparent on magnetic resonance imaging
      (MRI) than on radiograph or computed tomography scan. Management of these
      injuries included immobilization followed by surgery with particular care taken
      to avoid application of distraction forces to the neck. CONCLUSION: Patients with
      occipitocervical dissociation injuries may survive their injury and even retain
      neurologic integrity. Initial in-line head stabilization is emphasized to prevent
      catastrophic neurologic injury. The resting osseous relationships and vertebral
      alignment at the time of imaging evaluation may be deceivingly normal, and the
      damage often primarily or exclusively involves disruption of the perivertebral
      soft tissue structures. Prevertebral soft tissue swelling was apparent in all
      cases. For these injuries that involve primarily damage to the ligamentous
      structures, MRI seems to be the optimal test for revealing the magnitude of the
      injury.

PMID- 18628708
TI  - Clinical significance of ring apophysis fracture in adolescent lumbar disc
      herniation.
AB  - STUDY DESIGN: Retrospective review and post-test-only control group design.
      OBJECTIVE: To study the incidence and associated factors of ring apophysis
      fracture in adolescent lumbar disc herniation and to evaluate the long-term
      morbidity of untreated apophyseal fracture. SUMMARY OF BACKGROUND DATA: Ring
      apophysis fracture is a feature in adolescent disc herniation, but the incidence
      and prognosis are unknown. It is still controversial whether to remove the
      apophyseal fragment at time of discectomy. METHODS: We studied 96 adolescents
      (mean age, 14.7 years) with clinical diagnosis of disc herniation proved by
      computerized tomography (CT). In CT scan ring, apophyseal fracture is classified
      by the size (large/small) and the location (central/lateral). We used modified
      Oswestry classification in the nonoperative patients for pain and functional
      evaluation. Patients with and without apophyseal fracture were compared to define
      the significance of the lesion. RESULTS: Twenty-seven of the 96 CT studies (28%)
      demonstrated apophyseal fractures. All but 2 were at the level of the herniated
      disc. Large-central fragments were the most common in 16 patients (48%), large
      lateral fragments in 2, small-central fragments in 6, and small-lateral fragment
      in 6. Rate of surgery was significantly higher in the disc herniation patients
      with apophyseal fractures. Sixty-four nonoperative patients were evaluated 6.6
      years (range, 2.3-14.3) after the CT study and questionnaires were completed in
      54 patients (84%). Patients with large apophyseal fragments had more chance of
      chronic back pain and limitation of daily activities than the patients with small
      fragments and patients without apophyseal fracture. CONCLUSION: Apophyseal
      fracture is not uncommon in adolescent lumbar disc herniation. The surgical
      decision must depend on clinical symptoms instead of radiologic findings, but
      disc herniation with apophyseal fracture may exhibit more severe symptoms.
      Patients with large apophyseal fragments must be informed of a greater chance of
      chronic back pain later on. Small apophyseal fragments had no clinical
      significance.

PMID- 18628710
TI  - Efficacy of aprotinin as a blood conservation technique for adult deformity
      spinal surgery: a retrospective study.
AB  - STUDY DESIGN: A retrospective study that involved a total of 82 adult deformity
      patients who underwent spinal fusion surgery with instrumentation of 6 or more
      levels. OBJECTIVE: The purpose of this study is to assess the efficacy and safety
      of aprotinin in reducing blood loss in adult spinal deformity patients. SUMMARY
      OF BACKGROUND DATA: Aprotinin is an antifibrinolytic agent, which has been proven
      to be effective as a blood-conserving agent in cardiac surgery. This study
      focused specifically on adult spine deformity patients. METHODS: This
      retrospective study analyzed a total of 82 adult deformity patients (patients
      with diagnosis of adult scoliosis and kyphosis) who underwent spinal fusion
      surgery with instrumentation of 6 or more levels. Forty-one patients who received
      aprotinin were compared with a control group of 41 patients who did not receive
      aprotinin. Specific surgical outcome parameters and postoperative complications
      were assessed. RESULTS: The average age of the patients was 47 years and 41 years
      for the aprotinin group and the control group respectively. Thirty-nine percent
      of cases and 44% of controls had staged anterior/posterior fusion surgery, 39% of
      cases and 41% of controls underwent single stage posterior fusion surgery and the
      remaining 27% of cases and 15% of controls had same day anterior and posterior
      fusion surgery. The average number of levels fused and instrumented was 11.2 for
      the aprotinin group and 10.7 for the control group. The differences in mean blood
      loss and blood returned by cell-saver were statistically significantly lower in
      the aprotinin group (1324 mL vs. 2113 mL; P = 0.005 and 390 mL vs. 657 mL; P =
      0.003). The amount of drainage after surgery was similar (1421 mL vs. 1388 mL; P
      = 0.982). The aprotinin group received an average of 2.73 units of blood. This
      was significantly lower than the average 5.02 units that the controls received (P
      = 0.003). The rate of complications was comparable and no allergic reaction to
      aprotinin was noted. One case exhibited a transitory elevation of blood urea
      nitrogen/creatinine which resolved before discharge. CONCLUSION: The results of
      our study suggest that the administration of aprotinin is a safe and effective
      method to reduce blood loss and to decrease the need for transfusions without
      increasing risk of complication in the younger patients in relatively good
      general health undergoing spinal deformity surgery requiring 6 or more levels of
      fusion.

PMID- 18628709
TI  - Use of carboxymethylcellulose/polyethylene oxide gel in microdiscectomy with
      interlaminectomy: a case series comparison with long-term follow-up.
AB  - STUDY DESIGN: A consecutive, case series comparison. OBJECTIVE: To compare
      safety, long-term pain, and disability scores with and without use of
      carboxymethylcellulose/polyethylene oxide (CMC/PEO) gel after microdiscectomy
      with interlaminectomy. SUMMARY OF BACKGROUND DATA: Patient outcomes after
      microdiscectomy for lumbar disc herniation are frequently complicated by
      adhesions and fibrotic scars. Present management is controlled by good surgical
      technique as adhesion-reduction agents to date, have either proved ineffective or
      toxic. In 2002 a 100% synthetic combination of CMC/PEO, which reduces adhesions
      and fibrosis, became available across Europe as a gel application, (OXIPLEX/SP
      adhesion barrier gel FzioMed, Inc., San Luis Obispo, CA) and distributed under
      the trade names OXIPLEX/SP adhesion barrier gel (DePuy International, Ltd.,
      Leeds, United Kingdom) and MEDISHIELD adhesion barrier gel (Medtronic
      International Trading SARL, Tolochenaz, Switzerland). METHODS: A consecutive
      series of 70 patients with lumbar disc herniation undergoing microdiscectomy with
      interlaminectomy by the same surgeon were treated at the end of surgery with
      either CMC/PEO gel (N = 35) or no gel (N = 35). Treatments were allocated by an
      independent investigator. At presurgery and regular intervals over 3 years
      postsurgery, Oswestry disability index (ODI) and leg and back pain scores
      determined by visual analog scales (VAS), were assessed by a member of the
      surgical team blinded to the initial treatment allocation. RESULTS: Three years
      postsurgery reduction in disability as measured by the decrease in ODI compared
      with presurgery (mean +/- SD) was significantly (P < 0.05) greater with CMC/PEO
      than controls (-49.4 +/- 12.7 vs. -41 +/- 17.8). CMC/PEO treatment also resulted
      in significantly more patients having no disability as measured by reaching 0%
      ODI scores (15 CMC/PEO [43%] vs. 0 control group [0%]) (P < 0.01). Leg and back
      pain as measured by the decrease in VAS scores 3 years postsurgery were reduced
      with CMC/PEO compared with controls(leg -6.8 +/- 1.7 vs. -5.6 +/- 1.6, back -0.4
      +/- 1.5 vs. -0.1 +/- 2.0), P < 0.05 for leg pain. Importantly there were no
      safety issues and no differences in complications between the 2 treatment groups
      during the 30 day postoperative period. CONCLUSION: CMC/PEO gel after
      microdiscectomy with interlaminectomy appears safe to use and in a 3-year follow
      up significantly reduces disability and leg pain scores compared with our
      conventional treatment.

PMID- 18628711
TI  - Exercise therapy and low back pain: insights and proposals to improve the design,
      conduct, and reporting of clinical trials.
AB  - STUDY DESIGN: A report on plenary presentations and discussions of an expert
      panel and workshop ("Exercise as a treatment for subacute low back pain") that
      was held at the Amsterdam Forum VIII on Low Back Pain Research in Primary Care.
      OBJECTIVE: To highlight important issues regarding the design, conduct, and
      reporting of exercise trials and to provide suggestions for improvement in each
      domain. SUMMARY OF BACKGROUND DATA: Despite improvements in the methodologic
      quality of randomized clinical trials on low back pain (LBP), current trials on
      exercise therapy still show methodologic flaws in the design and reporting of
      studies. METHODS: Important issues in the design, conduct, and reporting of
      exercise trials for LBP were introduced by 4 presenters, and this was followed by
      a group discussion among 40 attendees. Conclusions and recommendations were
      extracted by the workshop panelists and summarized in this paper. RESULTS.:
      Workshop discussion led to the following recommendations: (1) specify a
      theoretical framework for exercise therapy for designing the intervention and
      selecting appropriate treatment efficacy measures; (2) to overcome blinding
      problems in exercise trials, include sham interventions and assess the success of
      blinding; (3) evaluate the role of patient-provider interactions through the use
      of self-report or observational measures; (4) to assure quality of treatment, use
      exercise interventions that reference existing exercise guidelines; (5) use
      subgroup analyses to identify subgroups of patients most likely to benefit; (6)
      in reporting exercise trials, include an extensive description of the study
      population, a detailed exercise protocol, and some measure of patient compliance;
      (7) further categorization of exercise interventions is needed, in terms of
      concept, mode, intensity, duration, frequency, and length; and (8)
      trial;1>registration and publication of detailed study protocols may help to
      strengthen the evidence-based concerning exercise therapy for LBP. CONCLUSION: By
      paying proper attention to issues concerning the design and reporting of exercise
      protocols when conducting future exercise trials, research may provide a stronger
      evidence basis for recommending or not recommending various exercise therapies
      for LBP.

PMID- 18628712
TI  - The effect of obesity on clinical outcomes after lumbar fusion.
AB  - STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: To investigate and
      compare back and leg pain, and health-related quality of life measures in obese
      patients undergoing lumbar spine fusion, and to compare the results to nonobese
      patients. SUMMARY OF BACKGROUND DATA: Obesity is a growing healthcare crisis in
      the United States and an increasing number of patients undergoing spinal surgery
      are obese. Obesity is also associated with low back pain. Some obese patients
      with significant structural spine problems may be dismissed as having their pain
      only coming from their weight. We compared patient outcomes in obese and nonobese
      patients undergoing lumbar fusion surgery. METHODS: We retrospectively reviewed a
      single-center patient database of patients undergoing lumbar fusion and
      identified 270 patients with greater than 2-year outcome data. Body mass index
      (BMI) was calculated and patients were classified as obese (BMI >or= 30) or
      nonobese (BMI < 30). All patients completed Oswestry Disability Index (ODI),
      Short Form (SF)-36 questionnaires, and back and leg pain numerical rating scores
      before surgery and at 2 years. We compared clinical outcomes and complication
      rates in the 2 groups. RESULTS: The overall study group consisted of 109 obese
      patients and 161 nonobese patients. Both the obese and nonobese patients
      demonstrated significant improvements in back pain, leg pain, SF-36 physical
      composite summary (PCS), and ODI scores (P < 0.001) at 2-year follow-up compared
      with baseline. There was no significant difference in the mean improvements seen
      in obese patients compared with nonobese patients with respect to back pain, leg
      pain, or SF-36 PCS or ODI scores. Both SF-36 PCS (P = 0.037) and ODI score (P =
      0.028) at 2-year follow-up were better in the nonobese patients compared with the
      obese patients. Overall complication rates were slightly higher in the obese
      group (P = 0.045), predominantly because of wound-related complications.
      CONCLUSION: Obese patients undergoing lumbar fusion achieve similar benefits to
      nonobese patients. Wound-related complications are more common in obese patients.
      Obese patients with otherwise good indications for lumbar fusion should not be
      denied this procedure because of their weight.

PMID- 18628713
TI  - Quantifying the effects of degeneration and other patient factors on lumbar
      segmental range of motion using multivariate analysis.
AB  - STUDY DESIGN: Retrospective review and multivariate analysis. OBJECTIVES: Assess
      lumbar spine segmental range of motion (ROM) with flexion/extension (F/E)
      radiographs and determine the relation to clinical variables. SUMMARY OF
      BACKGROUND DATA: Prior studies have investigated the roles of age and
      degeneration on lumbar segmental ROM only using univariate analyses. Multivariate
      analyses are also required to differentiate the multiple factors that may affect
      ROM and quantify their relative effects. METHODS: Radiographs of 258 patients
      were analyzed, including 137 females and 121 males with ages ranging from 18 to
      92 years. Segmental ROM and Kellgren score (KS) of degeneration were assessed for
      L1-S1. Multivariate regression analyses were performed for each level. Predicting
      variables evaluated were: (1) KS at the level of interest, (2) KS at the level
      above, (3) KS at the level below, (4) age, (5) gender, (6) weight, (7) height,
      (8) body mass index (BMI), and (9) smoking. Significance was defined as P < 0.05.
      RESULTS: Interobserver reliabilities for assessing KS (ICC 0.70) and segmental
      ROM (ICC 0.80) were good to excellent. In the multivariate analyses, age had a
      significant negative association with ROM at L1-L2, L2-L3, L3-L4, and L4-L5. BMI
      had a significant negative association with ROM at L2-L3, L3-L4, and L4-L5. KS at
      the level of interest had significant negative association with ROM only at L5
      S1. KS at adjacent levels, gender, weight, height, and smoking did not have a
      significant association with ROM at any level. CONCLUSION: The results of this
      study provide the clinician with insight into factors that influence segmental
      lumbar ROM. Age was the strongest statistical predictor of ROM and was associated
      with declining ROM, amounting to an approximate 3 degrees decrease in total
      sagittal lumbar ROM in the superior 4 segments every 10 years. BMI was another
      factor associated with lumbar ROM. Degeneration was a significant predictor of
      ROM only at L5-S1.

PMID- 18628714
TI  - Physical therapy for acute low back pain: associations with subsequent healthcare
      costs.
AB  - STUDY DESIGN: Case-control. OBJECTIVE: To examine the association between
      adherence to the evidence-based recommendation for active physical therapy care
      and clinical outcomes along with subsequent healthcare utilization and charges
      for 1 year after completion of physical therapy. SUMMARY OF BACKGROUND DATA: Low
      back pain (LBP) is a common condition associated with high costs. Many patients
      with acute LBP receive physical therapy. The type of physical therapy care
      provided may impact subsequent healthcare costs. METHODS: A retrospective review
      was undertaken of patients age 18-60 with acute (<90 days) LBP receiving physical
      therapy covered by 1 insurance provider. Adherence to the recommendation for
      active care was determined from billing records. Disability (Oswestry) and pain
      (numerical pain rating) were assessed at the beginning and completion of physical
      therapy. Subsequent healthcare utilization for LBP and charges were recorded from
      insurer's databases. RESULTS: Four hundred and seventy-one patients were included
      (mean age 41.2 years [SD = 11.0], 54% female), 28.0% received adherent care.
      Patients receiving adherent care had fewer physical therapy visits (mean
      difference 1.3 visits, P < 0.05) with lower charges (nontransformed mean
      difference $167, P < 0.05), greater improvement in pain (mean difference 12.3%,
      95% confidence interval [CI]: 3.2-21.3) and disability (mean difference 17.6%,
      95% CI: 11.1-24.1). During the year after discharge, receiving adherent care was
      associated with a lower likelihood of receiving prescription medication (46.2%
      vs. 57.2%, P < 0.05), magnetic resonance imaging (MRI) (8.3% vs. 15.9%, P <
      0.05), or epidural injections (5.3% vs. 12.1%, P < 0.05). CONCLUSION: Adherence
      to the recommendation for active care was associated with better clinical
      outcomes and decreased subsequent use of prescription medication, MRI, and
      injections. Improving adherence to this recommendation may present an opportunity
      to improve the cost-effectiveness of care for acute LBP.

PMID- 18628715
TI  - Sacral insufficiency fractures caudal to instrumented posterior lumbosacral
      arthrodesis.
AB  - STUDY DESIGN: Retrospective review of sacral insufficiency fractures. OBJECTIVE:
      Determine incidence of sacral insufficiency fractures after posterior lumbosacral
      fusion. Review the pertinent literature. Describe the ability of lumbopelvic
      fixation to restore the alignment of these fractures. SUMMARY OF BACKGROUND DATA:
      Fractures of the sacrum are rare injuries that have been described at the caudal
      end of lumbopelvic constructs. Without a high index of suspicion, this entity can
      be overlooked, causing a diagnostic delay. METHODS: Review of patients treated at
      our institution from 2002 to 2005. RESULTS: Nine patients meet our inclusion
      criteria. Sacral insufficiency fractures were recognized on an average of 5 weeks
      in the 6 patients with the index procedure performed at our institution
      (Incidence of fracture with short segment instrumentation is 1.3%, whereas long
      segment fixation has an incidence of 3.1%). The other 3 referred patients had an
      average delay in diagnosis of 8 months. Two patients underwent immediate fracture
      stabilization and fusion. The remaining 7 patients were initially treated
      nonoperatively. Four patients abandoned bracing an average of 3.3 months after
      initiation of treatment. For all of the surgical candidates, preoperative
      kyphosis measured 9.7 degrees and anterolisthesis averaged 10 mm. Postoperative
      measurement improved to a mean kyphosis of 2.3 degrees and mean displacement of
      1.2 mm. All operatively treated fractures healed and the patients regained their
      ambulatory capacity. CONCLUSION: Sacral insufficiency fractures are an uncommon
      complication of segmental posterior lumbosacral fixation in osteoporotic
      patients. They are potentially unstable fractures and kyphosis and displacement
      may contribute to persistent problems of pain and postural malalignment. The
      diagnosis may be difficult and should be considered in the differential diagnosis
      in patients who do not improve during the postoperative course. Lumbopelvic
      fixation is a useful salvage treatment modality for patients who fail
      nonoperative treatment.

PMID- 18628716
TI  - Re: Sasso RC, Foulk DM, Hahn M. Prospective, randomized trial of metal-on-metal
      artificial lumbar disc replacement: initial results for treatment of discogenic
      pain. Spine 2008;33:123-31.

PMID- 18628717
TI  - Effects of general anesthetic agents in adults receiving electroconvulsive
      therapy: a systematic review.
AB  - OBJECTIVES: Our primary objective was to conduct a systematic review to determine
      the differential effects of general anesthetic agents on electroconvulsive
      therapy (ECT) induced motor and electroencephalogram seizure duration. Our
      secondary objective was to determine the differential effects of induction agents
      on emergence time, recovery time, and the occurrence of adverse cardiac events
      and drug effects. MATERIALS AND METHODS: We searched 4 electronic databases for
      randomized, crossover, and parallel trials. The weighted mean difference was
      calculated for continuous variables, whereas the risk difference was assessed for
      dichotomous variables. We combined crossover- and parallel-designed trials using
      the inverse variance method, and the random-effects model was used throughout.
      RESULTS: Forty-one randomized trials involving 14 induction agents were included.
      The quality of trials was poor. Clinical and statistical heterogeneity were
      identified throughout. The most commonly studied comparison was methohexital
      versus propofol, where the mean motor seizure duration with methohexital was
      longer compared with that of propofol (weighted mean difference, 9.06 seconds;
      95% confidence interval, 5.72-12.40). However, combining methohexital or propofol
      with a short-acting opioid prolonged seizure duration. Small but significant
      variations in emergence and recovery times were identified. Inadequate data were
      available to draw conclusions regarding adverse cardiac events and drug effects.
      No deaths were reported. CONCLUSIONS: Whereas the relationship between ECT
      seizure length and efficacy remains unclear, all of the available induction
      agents in this review would be appropriate for ECT. When the clinician needs to
      prolong seizure length, methohexital or the addition of a short-acting opioid to
      methohexital or propofol should be considered. The small variations in emergence
      and recovery times should not govern the choice of an induction agent.

PMID- 18628721
TI  - Regression of uveal melanoma after plaque radiotherapy and thermotherapy based on
      chromosome 3 status.
AB  - PURPOSE: To evaluate regression rates after plaque radiotherapy and thermotherapy
      of uveal melanoma with chromosome 3 monosomy versus disomy. DESIGN:
      Noncomparative case series. PARTICIPANTS: Two hundred and seventy patients with
      uveal melanoma. METHODS: Fine needle aspiration biopsy was used at the time of
      plaque radiotherapy to sample tumor cells for genetic testing. MAIN OUTCOME
      MEASURES: Tumor thickness regression based on chromosome 3 status. RESULTS: At
      the time of plaque radiotherapy, the median tumor thickness was 4.0 mm for
      melanomas with chromosome 3 monosomy and 3.5 mm for those with disomy 3. The
      median tumor thickness (% original thickness) at 4, 8, 12, 15, and 18 months
      after radiotherapy for melanoma with monosomy 3 was 77%, 67%, 58%, 55%, and 50%
      and for those with disomy 3 was 82%, 70%, 69%, 67%, and 61%. The median monthly
      regression rate was 3.1% for tumors with monosomy 3 and 2.7% for those with
      disomy 3. The overall regression and monthly rate of regression was statistically
      greater at 12 months (P < 0.001) and 15 months (P = 0.003) for melanomas with
      monosomy 3 compared with disomy 3. CONCLUSIONS: Uveal melanomas with chromosome 3
      monosomy showed faster and greater tumor thickness regression at 12 and 15 months
      after plaque radiotherapy and thermotherapy than melanomas with disomy 3.

PMID- 18628722
TI  - Posterior hyaloid changes following intravitreal triamcinolone and macular laser
      for diffuse diabetic macular edema.
AB  - PURPOSE: To compare the effects of intravitreal triamcinolone and macular grid
      laser photocoagulation on the vitreomacular relationship in diffuse diabetic
      macular edema. METHODS: Review of optical coherence tomography images gathered in
      a prospective, interventional randomized clinical trial. SETTING: Institutional
      Practice. PROCEDURES: Seventy-seven optical coherence tomography images of 88
      consecutive patients entered into a randomized clinical trial of the treatment of
      persistent diffuse diabetic macular edema were reviewed by two independent
      observers. All patients in the trial had diabetic macular edema following at
      least two macular grid laser treatments and were randomized to intravitreal
      injections of 4 mg triamcinolone or to further macular grid laser. Optical
      coherence tomography images were recorded at baseline, 4, 8, and 12 months and
      the patterns of vitreomacular relationship were classified into six categories.
      MAIN OUTCOME MEASURES: The patterns of vitreomacular relationship in the two
      groups were compared and correlated with the response to treatment. Outcome
      measures were defined as changes in best-corrected visual acuity Early Treatment
      Diabetic Retinopathy Study letters and central macular thickness on optical
      coherence tomography. RESULTS: Six eyes had peri-foveal vitreous detachment with
      or without traction in each group at baseline. At 12 months, the prevalence of
      peri-foveal vitreous detachment was significantly higher after intravitreal
      triamcinolone (n = 11) than macular grid laser (n = 8). These patients had poorer
      visual outcome (P = 0.01) and increased central macular thickness (P = 0.002).
      The development of complete posterior vitreous detachment was associated with
      significantly decreased central macular thickness (P = 0.001) but not better
      visual outcome (P = 0.72). CONCLUSION: These results suggest that posterior
      hyaloid changes may play a more influential role in the response to intravitreal
      triamcinolone than laser treatment for diffuse diabetic macular edema.

PMID- 18628723
TI  - Solubility of triamcinolone acetonide and other anti-inflammatory drugs in
      silicone oil: implications for Therapeutic Efficacy.

PMID- 18628724
TI  - Predictors of anti-VEGF-associated retinal pigment epithelial tear using FA and
      OCT analysis.
AB  - PURPOSE: To identify fluorescein angiography and optical coherence tomography
      (OCT) predictors for retinal pigment epithelial (RPE) tear in eyes with pigment
      epithelium detachment (PED) associated with neovascular age-related macular
      degeneration treated with intravitreal vascular endothelial growth factor (VEGF)
      modulating therapy. DESIGN: Retrospective comparative case series. METHODS: In a
      single institutional center, 60 consecutive patients with PED and neovascular age
      related macular degeneration treated with VEGF modulating therapy (either
      pegaptanib, bevacizumab, or ranibizumab) for more than a 27-month period were
      included in the study. Fluorescein angiography (FA) and OCT imaging was performed
      before and after anti-VEGF therapy. Formal statistical analysis comparing the
      tear group to the nontear group was performed to identify high-risk features for
      RPE tear. RESULTS: RPE tear rate for eyes with vascularized PED receiving anti
      VEGF therapy was 17% (10/60). There were highly statistically significant
      differences in the median PED size on fluorescein angiography (greatest linear
      diameter) (3.2 mm versus 1.8 mm, respectively; P < 0.001) and in the median
      maximum PED height on OCT (394 mum versus 149 mum, respectively; P = 0.001)
      between the tear group and nontear group. There was also a significant difference
      in terms of the presence of subretinal fluid on OCT between the two groups (87.5%
      versus 39%, respectively; P = 0.019). CONCLUSION: Large PED basal diameter and
      vertical height are correlated with an increased risk of developing an RPE tear
      after anti-VEGF therapy. Patients with large vascularized PED by fluorescein
      angiography and/or OCT analysis should be alerted of the risk for vision loss due
      to RPE tear after anti-VEGF therapy.

PMID- 18628725
TI  - Outcome of fluocinolone acetonide implant (Retisert) reimplantation for chronic
      noninfectious posterior uveitis.

PMID- 18628726
TI  - Illumination and phototoxicity issues in vitreoretinal surgery.

PMID- 18628727
TI  - Preferred retinal locus in macular disease: characteristics and clinical
      implications.
AB  - PURPOSE: To investigate the location and fixation stability of preferred retinal
      locations (PRLs) in patients with macular disease, and the relationship among
      areas of abnormal fundus autofluorescence, the PRL and visual sensitivity.
      METHODS: Fifteen patients (15 eyes) were studied. Seven had Stargardt disease, 1
      bull's eye maculopathy, 5 age-related macular degeneration, 1 Best disease, and 1
      pattern dystrophy. All tested eyes had areas of abnormal fundus autofluorescence.
      The PRL was evaluated with fundus photography and the Nidek microperimeter.
      Visual field sensitivity was measured with the Nidek microperimeter. RESULTS: Of
      the 15 eyes, 4 had foveal and 11 had eccentric fixation. Eccentric PRLs were
      above the atrophic lesion and their stability did not depend on the degree of
      eccentricity from the fovea. Visual sensitivity was markedly decreased in
      locations corresponding to hypofluorescent areas. Sensitivity was not decreased
      in hyperfluorescent areas corresponding to flecks but was decreased if
      hyperfluorescence was in the form of dense annuli. CONCLUSION: Eccentric PRLs
      were in the superior retina in regions of normal fundus autofluorescence.
      Fixation stability was not correlated with the degree of eccentricity from the
      fovea. To assess the outcomes of treatment trials it is important to use methods
      that relate retinal morphology to visual function.

PMID- 18628728
TI  - Childhood CNS vasculitis: a treatable cause of new neurological deficit in
      children.

PMID- 18628729
TI  - The challenges of determining RA disease activity and remission in clinical
      practice.

PMID- 18628730
TI  - Strengthening resilience capacity might light the way to a brighter future for
      patients with fibromyalgia.

PMID- 18628731
TI  - How effective is nutritional supplementation for the prevention of stress
      fractures in female military recruits?
AB  - Intensive physical training can cause stress fractures in both osteoporotic
      patients and healthy, young adults. Female military recruits are especially
      vulnerable to such fractures, with a reported frequency of 5-15% during prolonged
      periods of intense physical activity. In this Practice Point commentary, I
      discuss a randomized, controlled study of nutritional supplementation for
      prevention of stress fractures in female US navy recruits. Lappe et al. reported
      that intervention with a high dose of calcium (2g daily) plus a normal dose of
      vitamin D(3) (800IU daily) reduced the incidence of stress fractures by 20%
      (P<0.003) during the 8-week study period. The authors also confirmed additional
      risk factors for stress fractures, such as smoking, low physical fitness and
      amenorrhea. Predisposing risk factors and nutritional intervention strategies
      that influence stress fracture occurrence in young adults at the time of their
      peak bone mass, therefore, seem very similar to those known to affect
      osteoporotic fractures in the elderly.

PMID- 18628732
TI  - Gonadotropin-releasing hormone analogs in fertility preservation-lack of
      biological basis?
AB  - In this Practice Point commentary, we discuss the results and limitations of a
      nonrandomized, retrospective-prospective study of gonadotropin-releasing hormone
      analogs (GnRHa) in women with Hodgkin disease. Blumenfeld et al. concluded that
      coadministration of GnRHa during chemotherapy preserved cyclic ovarian function
      but not fertility. As the endocrine and ovulatory functions of the ovary are
      connected, this conclusion seems implausible. The study did not control for
      disease severity or the dose of alkylating agents. In addition, GnRHa treatment
      was not randomized, so patients in the control group were unlikely to have
      received GnRHa because the severity of their disease resulted in more-aggressive
      chemotherapy. By contrast, the only randomized study published to date showed no
      gonadal protection from GnRHa during chemotherapy in either sex. Furthermore,
      GnRHa did not prevent primordial-follicle loss in a human ovarian xenograft
      model. Unless a larger prospective study proves otherwise, GnRHa should not be
      offered as a proven method of fertility preservation.

PMID- 18628733
TI  - Is radiofrequency ablation the treatment of choice for patients with small
      hepatocellular carcinoma?
AB  - Liver resection is widely considered the mainstay of curative therapy for small
      hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) was initially
      developed as a treatment for small HCC in patients with considerable cirrhosis
      and inadequate liver function reserve for liver resection. However, in some
      centers, RFA is now used for small HCC, as an alternative to liver resection or
      even as the preferred treatment. This Practice Point commentary discusses the
      findings and limitations of a retrospective cohort study by Livraghi et al. that
      analyzed the outcomes of a group of patients with small, single HCC who underwent
      treatment with RFA. The authors reported a low major complication rate and a
      local complete response rate similar to that after resection. This commentary
      highlights the issues to consider when interpreting and generalizing these
      results, in particular that these findings need to be interpreted in the light of
      studies that suggest a high rate of local recurrence and incomplete
      histopathological response after RFA of small HCC.

PMID- 18628734
TI  - Should urgent ERCP be performed in patients with acute biliary pancreatitis
      without acute cholangitis?
AB  - Endoscopists who perform endoscopic retrograde cholangiopancreatography (ERCP)
      are frequently pressured to perform urgent (usually night or weekend) ERCP in
      patients with acute biliary pancreatitis in the belief that this procedure
      reduces morbidity and mortality. However, with the exception of those patients
      with concurrent acute cholangitis, data that urgent ERCP with biliary compression
      is helpful in all patients with acute gallstone pancreatitis are lacking. In this
      Practice Point commentary, I discuss the findings and limitations of a meta
      analysis conducted by Petrov et al. that pooled data from three randomized,
      controlled trials that included 450 patients in total. Four other randomized,
      controlled trials on this topic were excluded from the analysis because of
      methodologic problems. The authors concluded that early ERCP was not associated
      with a significant reduction in complications or mortality in patients with
      predicted mild or severe acute biliary pancreatitis.

PMID- 18628735
TI  - What is the potential role of antifibrotic agents for the treatment of liver
      disease?

PMID- 18628736
TI  - Should patients undergoing ERCP be placed in the prone or supine position?
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is generally performed in
      the prone or semi-prone position. Compared with the supine position, the left
      lateral and prone positions are believed to carry a lower risk of aspiration,
      allow easier intubation of the esophagus and provide a more comfortable position
      for the endoscopist. However, the supine position might be advantageous for the
      evaluation of pancreatic and biliary anatomy and for enhanced control of the
      airway. In this Practice Point commentary, I discuss the findings and limitations
      of a prospective, randomized study conducted by Tringali et al. that compared the
      performance of ERCP in the prone and supine positions by both experienced
      endoscopists and trainees. The results suggest no difference in the difficulty of
      the procedure on the basis of patient position. Objective measurements including
      mean time to visualize the papilla and opacification of the desired duct were no
      different. Likewise, overall technical success and complication rates were
      equivalent. These results suggest that either the supine or prone positions are
      adequate for the technical performance of ERCP. This commentary highlights the
      issues to consider when interpreting and generalizing these results in clinical
      practice.

PMID- 18628737
TI  - Is the addition of cisplatin to S-1 better than S-1 alone for patients with
      advanced gastroesophageal cancer?
AB  - The investigators of the recent phase III SPIRITS trial found that the addition
      of cisplatin to S-1 (a fourth generation oral fluoropyrimidine) provided a
      significant overall survival advantage (P = 0.04) over treatment with S-1 alone
      among previously untreated patients with advanced gastric cancer. In addition,
      the combination had an acceptable safety profile. This trial establishes a new
      first-line standard treatment for patients with advanced gastric cancer in Japan.
      Level 1 evidence for prolonged survival of patients with advanced
      gastroesophageal cancer has been established for docetaxel (V-325 trial) and
      cisplatin (SPIRITS trial) but not for S-1. Fluoropyrimidines (S-1 included) have
      been considered part of standard front-line therapy without the establishment of
      level 1 evidence for prolonging survival. The future lies in the rapid
      incorporation of biologic agents in combination with cytotoxics, with a continued
      focus on safety and convenience, and efforts to individualize therapy for each
      patient. Individualized therapy may be defined as the selection of optimum
      treatment for a specific patient on the basis of knowledge of the cancer's
      genetic and epigenetic alterations and the patient's genotype.

PMID- 18628738
TI  - Mechanisms of Disease: signal transduction in lung carcinogenesis -- a comparison
      of smokers and never-smokers.
AB  - Although smoking has been established as the most important cause of lung cancer,
      approximately 10% of patients with this malignancy have no history of smoking.
      The pathogenesis of tobacco-related lung carcinogenesis is becoming well
      characterized, but the molecular mechanisms of neoplastic transformation in never
      smokers have not yet been adequately elucidated. Nevertheless, numerous recent
      studies have revealed a distinct biological process of malignant transformation
      with unique epidemiological and clinicopathological characteristics in never
      smokers. The molecular pathways involved in the differential pattern of lung
      oncogenesis according to smoking status, however, remain fairly obscure.
      Researchers have studied several molecular pathways implicated in lung
      carcinogenesis in smokers and never-smokers, examining these processes at the
      genomic, epigenetic and proteomic level. The differential protein expression
      according to smoking status in critical signal transduction pathways has
      attracted scientific interest because of the possibilities of therapeutic
      intervention. In this Review we describe the best-characterized signaling
      pathways implicated in the transduction of proliferative signals and discuss the
      activity of these pathways in smokers and never-smokers.

PMID- 18628739
TI  - Intermittent androgen blockade should be regarded as standard therapy in prostate
      cancer.

PMID- 18628740
TI  - Assessing the benefits and harms of statin treatment in patients with chronic
      kidney disease.
AB  - This Practice Point commentary discusses a meta-analysis by Strippoli et al. that
      included 50 randomized and quasi-randomized trials of statins in patients with
      different stages of kidney disease (predialysis, dialysis and transplantation; n
      = 30,144). The authors found that statins safely reduced lipid concentrations and
      the risk of cardiovascular events and cardiovascular mortality, but that the
      agents had no effect on all-cause mortality overall and had uncertain
      renoprotective effects. The analysis was comprehensive and well executed. A
      decreased risk of all-cause mortality with statins was found in studies of
      predialysis patients but not in studies of renal transplant recipients or
      patients on chronic dialysis. Statin doses used in the trials were well tolerated
      and safe in all subgroups of patients with chronic kidney disease; therefore, we
      feel that statin use to maintain LDL cholesterol below 100 mg/dl (2.6 mmol/l)
      should be initiated to potentially decrease cardiovascular risk in such patients.
      The benefits of statin therapy on all-cause mortality and the clinically
      significant benefits of this treatment on progression of kidney disease are still
      unclear, and additional trial evidence in patients with chronic kidney disease is
      needed.

PMID- 18628741
TI  - Glycated hemoglobin or glycated albumin for assessment of glycemic control in
      hemodialysis patients with diabetes?
AB  - This commentary discusses the findings of a study by Peacock et al., who measured
      levels of glycated hemoglobin (HbA(1c)) and glycated albumin in patients with
      diabetes who either were or were not on hemodialysis in an effort to determine
      which marker is the better indicator of glycemic control. They found that HbA(1c)
      and glycated albumin levels are both independently associated with serum glucose
      level. However, HbA(1c) level--unlike glycated albumin level--was also influenced
      by hemodialysis, hemoglobin level, and erythropoietin dose. Although we agree
      that glycated albumin level could be a better indicator of glycemic control than
      HbA(1c) level in patients on hemodialysis who have diabetes and anuria, this
      conclusion might not be applicable to patients with massive proteinuria or to
      those on peritoneal dialysis. Further studies are required to confirm the target
      glycated albumin level that is necessary to ensure a good prognosis for patients
      with diabetes who are on hemodialysis because no clear consensus has yet been
      reached. In addition, more data are needed to determine at which stage of kidney
      disease measurement of glycated albumin levels becomes preferable to assessment
      of HbA(1c) level.

PMID- 18628742
TI  - How should women with pre-eclampsia be followed up? New insights from mechanistic
      studies.
AB  - Understanding of the maternal syndrome of pre-eclampsia has greatly improved over
      the past 5 years. Specifically, the notion has emerged that the placenta is a
      source of antiangiogenic factors, such as soluble fms-like tyrosine kinase 1,
      that can progressively impair the mother's vascular and glomerular function
      throughout pregnancy. This impairment can be harmless during normal pregnancy,
      but in cases of defective placentation, concentrations of antiangiogenic factors
      increase to a level that compromises vital vascular functions in the short term
      and jeopardizes long-term maternal and fetal outcomes. In both pre-eclamptic and
      healthy pregnancies, the transient imbalance between angiogenic and
      antiangiogenic factors elicited by pregnancy acts as a 'stress test' for the
      endothelium, particularly in the glomerular capillary bed. Women who do not pass
      this test (i.e. those who develop pre-eclampsia or gestational hypertension)
      should be screened for glomerular disease, and their cardiovascular risk should
      be carefully monitored throughout life.

PMID- 18628743
TI  - Parasites lead to evolution of robustness against gene loss in host signaling
      networks.
AB  - Many biological networks can maintain their function against single gene loss.
      However, the evolutionary mechanisms responsible for such robustness remain
      unclear. Here, we demonstrate that antagonistic host-parasite interactions can
      act as a selective pressure driving the emergence of robustness against gene
      loss. Using a model of host signaling networks and simulating their coevolution
      with parasites that interfere with network function, we find that networks evolve
      both redundancy and specific architectures that allow them to maintain their
      response despite removal of proteins. We show that when the parasite pressure is
      removed, subsequent evolution can lead to loss of redundancy while architecture
      based robustness is retained. Contrary to intuition, increased parasite virulence
      hampers evolution of robustness by limiting the generation of population level
      diversity in the host. However, when robustness emerges under high virulence, it
      tends to be stronger. These findings predict an increased presence of robustness
      mechanisms in biological networks operating under parasite interference.
      Conversely, the presence of such mechanisms could indicate current or past
      parasite interference.

PMID- 18628744
TI  - The incoherent feed-forward loop can generate non-monotonic input functions for
      genes.
AB  - Gene regulation networks contain recurring circuit patterns called network
      motifs. One of the most common network motif is the incoherent type 1 feed
      forward loop (I1-FFL), in which an activator controls both gene and repressor of
      that gene. This motif was shown to act as a pulse generator and response
      accelerator of gene expression. Here we consider an additional function of this
      motif: the I1-FFL can generate a non-monotonic dependence of gene expression on
      the input signal. Here, we study this experimentally in the galactose system of
      Escherichia coli, which is regulated by an I1-FFL. The promoter activity of two
      of the gal operons, galETK and galP, peaks at intermediate levels of the signal
      cAMP. We find that mutants in which the I1-FFL is disrupted lose this non
      monotonic behavior, and instead display monotonic input functions. Theoretical
      analysis suggests that non-monotonic input functions can be achieved for a wide
      range of parameters by the I1-FFL. The models also suggest regimes where a
      monotonic input-function can occur, as observed in the mglBAC operon regulated by
      the same I1-FFL. The present study thus experimentally demonstrates how upstream
      circuitry can affect gene input functions and how an I1-FFL functions within its
      natural context in the cell.

PMID- 18628745
TI  - Top-down systems biology integration of conditional prebiotic modulated
      transgenomic interactions in a humanized microbiome mouse model.
AB  - Gut microbiome-host metabolic interactions affect human health and can be
      modified by probiotic and prebiotic supplementation. Here, we have assessed the
      effects of consumption of a combination of probiotics (Lactobacillus paracasei or
      L. rhamnosus) and two galactosyl-oligosaccharide prebiotics on the symbiotic
      microbiome-mammalian supersystem using integrative metabolic profiling and
      modeling of multiple compartments in germ-free mice inoculated with a model of
      human baby microbiota. We have shown specific impacts of two prebiotics on the
      microbial populations of HBM mice when co-administered with two probiotics. We
      observed an increase in the populations of Bifidobacterium longum and B. breve,
      and a reduction in Clostridium perfringens, which were more marked when combining
      prebiotics with L. rhamnosus. In turn, these microbial effects were associated
      with modulation of a range of host metabolic pathways observed via changes in
      lipid profiles, gluconeogenesis, and amino-acid and methylamine metabolism
      associated to fermentation of carbohydrates by different bacterial strains. These
      results provide evidence for the potential use of prebiotics for beneficially
      modifying the gut microbial balance as well as host energy and lipid homeostasis.

PMID- 18628746
TI  - Membrane identity and GTPase cascades regulated by toggle and cut-out switches.
AB  - Key cellular functions and developmental processes rely on cascades of GTPases.
      GTPases of the Rab family provide a molecular ID code to the generation,
      maintenance and transport of intracellular compartments. Here, we addressed the
      molecular design principles of endocytosis by focusing on the conversion of early
      endosomes into late endosomes, which entails replacement of Rab5 by Rab7. We
      modelled this process as a cascade of functional modules of interacting Rab
      GTPases. We demonstrate that intermodule interactions share similarities with the
      toggle switch described for the cell cycle. However, Rab5-to-Rab7 conversion is
      rather based on a newly characterized 'cut-out switch' analogous to an electrical
      safety-breaker. Both designs require cooperativity of auto-activation loops when
      coupled to a large pool of cytoplasmic proteins. Live cell imaging and endosome
      tracking provide experimental support to the cut-out switch in cargo progression
      and conversion of endosome identity along the degradative pathway. We propose
      that, by reconciling module performance with progression of activity, the cut-out
      switch design could underlie the integration of modules in regulatory cascades
      from a broad range of biological processes.

PMID- 18628747
TI  - Comment on 'Dynamic analysis of optimality in myocardial energy metabolism under
      normal and ischemic conditions'.

PMID- 18628750
TI  - FDG, MET or CHO? The quest for the optimal PET tracer for glioma imaging
      continues.
AB  - This Practice Point commentary discusses a study by Kato et al. that assessed the
      usefulness of three PET tracers--(11)C-methionine (MET), (18)F
      fluorodeoxyglucose, and (11)C-choline--for the metabolic evaluation of gliomas.
      The authors measured the ratio of tumor uptake to normal brain uptake (T/N
      ratio), with the frontal cortex as reference region, and analyzed the
      correlations between tracer uptake and tumor grade, type, and proliferation
      activity. Whereas all three tracers showed a similar correlation between the T/N
      ratio and tumor grade in astrocytic and oligodendroglial tumors, MET proved to be
      the most user-friendly marker in all gliomas as it enables the straightforward
      localization of 'hot lesions' and provides outstanding quantitative metabolic
      parameters. Here we highlight a few methodological issues arising from Kato et
      al.'s study and, consequently, we urge the PET community to reach a consensus on
      an objective approach towards the evaluation of PET tracers in the field of neuro
      oncology.

PMID- 18628749
TI  - From E-MAPs to module maps: dissecting quantitative genetic interactions using
      physical interactions.
AB  - Recent technological breakthroughs allow the quantification of hundreds of
      thousands of genetic interactions (GIs) in Saccharomyces cerevisiae. The
      interpretation of these data is often difficult, but it can be improved by the
      joint analysis of GIs along with complementary data types. Here, we describe a
      novel methodology that integrates genetic and physical interaction data. We use
      our method to identify a collection of functional modules related to chromosomal
      biology and to investigate the relations among them. We show how the resulting
      map of modules provides clues for the elucidation of function both at the level
      of individual genes and at the level of functional modules.

PMID- 18628751
TI  - Cancer stem cells and glioma.
AB  - Despite continued advances in surgical and medical therapies, the outcomes for
      patients diagnosed with glioblastoma multiforme remain dismal. Recent data
      suggest that progression of these brain tumors is driven by a small subpopulation
      of tumor cells, which are termed cancer stem cells (CSCs) because of their
      capability to self-renew, proliferate and give rise to progeny of multiple
      neuroepithelial lineages. According to the CSC hypothesis, current therapies that
      are extremely cytotoxic to the bulk of highly proliferative tumor cells fail to
      obliterate the relatively quiescent and resistant CSC compartment, thereby
      allowing these cells to survive and drive tumor recurrence. This Review
      summarizes current knowledge regarding neural stem cells in the normal adult
      brain and CSCs in glial tumors and discusses the implications of the CSC
      hypothesis for the development of future therapies for brain tumors.

PMID- 18628752
TI  - Transcranial ultrasound in the diagnosis of Parkinson's disease.

PMID- 18628753
TI  - The roles of melatonin and light in the pathophysiology and treatment of
      circadian rhythm sleep disorders.
AB  - Normal circadian rhythms are synchronized to a regular 24 h environmental light
      dark cycle, and the suprachiasmatic nucleus and the hormone melatonin have
      important roles in this process. Desynchronization of circadian rhythms, as
      occurs in chronobiological disorders, can produce severe disturbances in sleep
      patterns. According to the International Classification of Sleep Disorders,
      circadian rhythm sleep disorders (CRSDs) include delayed sleep phase syndrome,
      advanced sleep phase syndrome, non-24 h sleep-wake disorder, jet lag and shift
      work sleep disorder. Disturbances in the circadian phase position of plasma
      melatonin levels have been documented in all of these disorders. There is
      compelling evidence to implicate endogenous melatonin as an important mediator in
      CRSD pathophysiology, although further research involving large numbers of
      patients will be required to clarify whether the disruption of melatonin
      secretion is a causal factor in CRSDs. In this Review, we focus on the use of
      exogenous melatonin and light therapy to treat the disturbed sleep-wake rhythms
      seen in CRSDs.

PMID- 18628754
TI  - Advances in high-capacity extrachromosomal vector technology: episomal
      maintenance, vector delivery, and transgene expression.
AB  - Recent developments in extrachromosomal vector technology have offered new ways
      of designing safer, physiologically regulated vectors for gene therapy.
      Extrachromosomal, or episomal, persistence in the nucleus of transduced cells
      offers a safer alternative to integrating vectors which have become the subject
      of safety concerns following serious adverse events in recent clinical trials.
      Extrachromosomal vectors do not cause physical disruption in the host genome,
      making these vectors safe and suitable tools for several gene therapy targets,
      including stem cells. Moreover, the high insert capacity of extrachromosomal
      vectors allows expression of a therapeutic transgene from the context of its
      genomic DNA sequence, providing an elegant way to express normal splice variants
      and achieve physiologically regulated levels of expression. Here, we describe
      past and recent advances in the development of several different extrachromosomal
      systems, discuss their retention mechanisms, and evaluate their use as expression
      vectors to deliver and express genomic DNA loci. We also discuss a variety of
      delivery systems, viral and nonviral, which have been used to deliver episomal
      vectors to target cells in vitro and in vivo. Finally, we explore the potential
      for the delivery and expression of extrachromosomal transgenes in stem cells. The
      long-term persistence of extrachromosomal vectors combined with the potential for
      stem cell proliferation and differentiation into a wide range of cell types
      offers an exciting prospect for therapeutic interventions.

PMID- 18628755
TI  - RNA interference screen to identify pathways that enhance or reduce nonviral gene
      transfer during lipofection.
AB  - Some barriers to DNA lipofection are well characterized; however, there is as yet
      no method of finding unknown pathways that impact the process. A druggable genome
      small-interfering RNA (siRNA) screen against 5,520 genes was tested for its
      effect on lipofection of human aortic endothelial cells (HAECs). We found 130
      gene targets which, when silenced by pooled siRNAs (three siRNAs per gene),
      resulted in enhanced luminescence after lipofection (86 gene targets showed
      reduced expression). In confirmation tests with single siRNAs, 18 of the 130 hits
      showed enhanced lipofection with two or more individual siRNAs in the absence of
      cytotoxicity. Of these confirmed gene targets, we identified five leading
      candidates, two of which are isoforms of the regulatory subunit of protein
      phosphatase 2A (PP2A). The best candidate siRNA targeted the PPP2R2C gene and
      produced a 65% increase in luminescence from lipofection, with a quantitative PCR
      validated knockdown of approximately 76%. Flow cytometric analysis confirmed that
      the silencing of the PPP2R2C gene resulted in an improvement of 10% in
      transfection efficiency, thereby demonstrating an increase in the number of
      transfected cells. These results show that an RNA interference (RNAi) high
      throughput screen (HTS) can be applied to nonviral gene transfer. We have also
      demonstrated that siRNAs can be co-delivered with lipofected DNA to increase the
      transfection efficiency in vitro.

PMID- 18628756
TI  - Intranigral lentiviral delivery of dominant-negative TNF attenuates
      neurodegeneration and behavioral deficits in hemiparkinsonian rats.
AB  - Neuroinflammatory processes have been implicated in the progressive loss of
      ventral midbrain dopaminergic (DA) neurons that give rise to Parkinson's disease
      (PD), a late-onset movement disorder that affects 2% of the population over the
      age of 70 years. We have shown earlier, in two rat models of PD, that inhibition
      of the proinflammatory cytokine tumor necrosis factor (TNF) through nigral
      infusion of dominant-negative (DN-TNF) protein (XENP345) attenuates DA neuron
      loss. The objectives of this study were to develop a constitutive lentiviral
      vector encoding dominate-negative TNF, and to determine whether a gene therapy
      approach to deliver DN-TNF directly into the rodent substantia nigra could
      prevent or attenuate neurotoxin-induced DA neuron loss and associated behavioral
      deficits. Here we demonstrate that a single injection of lentivirus-expressing DN
      TNF into rat substantia nigra, administered concomitant with a striatal 6
      hydroxydopamine lesion, results in sufficiently high expression of inhibitor in
      vivo to attenuate both DA neuron loss and behavioral deficits resulting from
      striatal dopamine depletion. Our findings demonstrate the feasibility and
      efficacy of dominant-negative TNF gene transfer as a novel neuroprotective
      strategy to prevent or delay nigrostriatal pathway degeneration. This strategy
      holds the potential for therapeutic application in the treatment of PD.

PMID- 18628757
TI  - Acid sphingomyelinase overexpression enhances the antineoplastic effects of
      irradiation in vitro and in vivo.
AB  - Exposure of cells or animals to stress frequently induces acid sphingomyelinase
      (ASM)-mediated ceramide production that leads to cell death. Consistent with
      this, overexpression of ASM in subcutaneous B16-F10 mouse melanomas, in
      combination with irradiation, resulted in tumors that were up to 12-fold smaller
      than irradiated control melanomas. Similarly, when irradiated melanomas were
      pretreated with a single, peritumoral injection of recombinant ASM (rhASM), the
      tumors were up to threefold smaller. The in vivo effect of ASM was likely due to
      enhanced cell death of the tumor cells themselves, as well as the surrounding
      microvascular endothelial cells. In vitro, rhASM had little or no effect on the
      growth of tumor cells, even in combination with irradiation. However, when the
      culture media was acidified to mimic the acidic microenvironment of solid tumors,
      rhASM-mediated cell death was markedly enhanced when combined with irradiation.
      Microscopic analysis suggested that this was associated with an increase in
      autophagy. rhASM has been produced for the treatment of the lysosomal storage
      disorder, type B Niemann-Pick disease, and is currently being evaluated in a
      phase-1 clinical trial. Based on the data presented in this article, we propose
      that further investigation of this protein and gene as antineoplastic agents also
      is warranted.

PMID- 18628758
TI  - The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular,
      and anti-HBV activities in patients with hepatocellular carcinoma.
AB  - JX-594 is a targeted oncolytic poxvirus that is designed to eradicate cancer
      cells having cell-cycle defects, through replication, cell lysis, and spread
      within tumors; oncolysis-induced tumor vascular shutdown and immunostimulation
      are augmented by granulocyte monocyte-colony-stimulating factor (GM-CSF)
      transgene expression. We have previously shown, in animal models of
      hepatocellular carcinoma (HCC), that JX-594 is a promising anticancer agent. We
      tested JX-594 in three patients with advanced refractory hepatitis B virus (HBV)
      associated HCC through intratumoral administration. JX-594 treatment was well
      tolerated and resulted in antitumoral efficacy in all three patients, despite the
      presence of high levels of neutralizing antibodies. JX-594 replication, its
      release into the circulation, distant tumor targeting were demonstrated. JX-594
      administration resulted in the induction of antivascular cytokines, and was
      associated with tumor vascular shutdown. We also showed, for the first time, that
      oncolytic virotherapy can suppress underlying HBV replication in HCC patients,
      and that tumor tissue could be the primary source of acute HBV replication and
      acute post-treatment HBV release. JX-594 treatment in HBV-associated HCC warrants
      further clinical testing; a Phase II trial is underway.

PMID- 18628759
TI  - Modification of second cancer risk after malignant melanoma by parental history
      of cancer.
AB  - The Swedish Family-Cancer Database was used to quantify the incidence of second
      tumours in melanoma patients with a parental history of cancer. Patients with
      parents affected by melanoma showed a 32.3-fold risk of second primary melanomas,
      which was greater than a multiplicative interaction.

PMID- 18628760
TI  - Should colorectal cancer screening start at the same age in European countries?
      Contributions from descriptive epidemiology.
AB  - We assessed incidence and mortality of colorectal cancer (CRC) at various ages
      among women and men in 38 European countries. The ages at which defined levels of
      incidence and mortality were reached varied between 9 and 17 years between
      countries. This variation requires consideration in the definition of screening
      guidelines.

PMID- 18628762
TI  - Second breast cancers in a Tuscan case series: characteristics, prognosis, and
      predictors of survival.
AB  - Little is known about long-term outcomes following a second breast cancer
      diagnosis. We describe the epidemiology, characteristics and prognosis of second
      breast cancers in an Italian cohort. We identified women with two breast cancer
      diagnoses from 24 278 histology records at a Tuscan breast cancer service between
      1980 and 2005, and determined their survival status. Disease-specific survival
      from second diagnosis was examined using Cox regression analyses. Second cancers
      were identified in 1044 women with a median age of 60 years. In all 455 were
      ipsilateral relapses and 589 were contralateral cancers. Median time between
      first and second diagnosis was 63.4 months. The majority of second cancers was
      small invasive or in situ tumours. Estimated 10-year survival from a second
      cancer diagnosis was 78%. Survival was poorest when the second cancer was large
      (HR=2.26) or node-positive (HR=3.43), when the time between the two diagnoses was
      <5 years (HR=1.45), or when the diagnosis was in an earlier epoch (HR=2.20).
      Second tumours were more likely to be large or node-positive if the first breast
      cancer had these features. Prognosis following a second breast cancer in this
      cohort was generally good. However, large or node-positive second tumours, and
      shorter intervals between diagnoses were indicators of poorer survival.

PMID- 18628761
TI  - Obesity and risk of pancreatic cancer among postmenopausal women: the Women's
      Health Initiative (United States).
AB  - A total of 138,503 women in the Women's Health Initiative in the United States
      were followed (for an average of 7.7 years) through 12 September 2005 to examine
      obesity, especially central obesity in relation to pancreatic cancer (n=251).
      Women in the highest quintile of waist-to-hip ratio had 70% (95% confidence
      interval 10-160%) excess risk of pancreatic cancer compared with women in the
      lowest quintile.

PMID- 18628763
TI  - Human papillomavirus and vaccination: knowledge, attitudes, and behavioural
      intention in adolescents and young women in Italy.
AB  - This study assesses knowledge, attitudes, and behavioural intention towards human
      papillomavirus (HPV) infection and vaccination in a random sample of 1348
      adolescents and young women aged 14-24 years in Italy. A self-administered
      anonymous questionnaire covered demographics; knowledge about HPV infection,
      cervical cancer, and HPV vaccine; the perceived risk for contracting HPV
      infection and/or for developing cervical cancer, the perceived benefits of a
      vaccination to prevent cervical cancer, and willingness to receive an HPV
      vaccine. Only 23.3% have heard that HPV is an infection of the genital mucosa and
      about cervical cancer. Those older, with at least one parent who is a health care
      professional, with personal, familiar, or friendly history of cervical cancer,
      and having underwent a health checkup in the last year with information about HPV
      vaccination were significantly more knowledgeable. Risk perception scores (range:
      1-10) of contracting HPV infection and of developing cervical cancer were 5.8 and
      6.5. Older age, not having a parent who is a health care professional, having had
      a personal, familiar, or friendly history of cervical cancer, and need of
      additional information were predictors of the perceived susceptibility of
      developing cervical cancer. The vast majority professed intent to receive an HPV
      vaccine and the significant predictors were having at least one parent who is a
      health care professional, a high perceived risk of contracting HPV infection and
      of developing cervical cancer, and a high belief towards the utility of a
      vaccination for preventing cervical cancer. Knowledge about HPV infection and
      cervical cancer should be improved with more attention to the benefit of HPV
      vaccination.

PMID- 18628764
TI  - The ErbB signalling pathway: protein expression and prognostic value in
      epithelial ovarian cancer.
AB  - Ovarian cancer is the most frequent cause of death from gynaecological cancer in
      the Western world. Current prognostic factors do not allow reliable prediction of
      response to chemotherapy and survival for individual ovarian cancer patients.
      Epidermal growth factor receptor (EGFR) and HER-2/neu are frequently expressed in
      ovarian cancer but their prognostic value remains unclear. In this study, we
      investigated the expression and prognostic value of EGFR, EGFR variant III
      (EGFRvIII), HER-2/neu and important downstream signalling components in a large
      series of epithelial ovarian cancer patients. Immunohistochemical staining of
      EGFR, pEGFR, EGFRvIII, Her-2/neu, PTEN (phosphatase and tensin homologue deleted
      on chromosome 10), total and phosphorylated AKT (pAKT) and phosphorylated ERK
      (pERK) was performed in 232 primary tumours using the tissue microarray platform
      and related to clinicopathological characteristics and survival. In addition,
      EGFRvIII expression was determined in 45 tumours by RT-PCR. Our results show that
      negative PTEN immunostaining was associated with stage I/II disease (P=0.006),
      non-serous tumour type (P=0.042) and in multivariate analysis with a longer
      progression-free survival (P=0.015). Negative PTEN staining also predicted
      improved progression-free survival in patients with grade III or undifferentiated
      serous carcinomas (P=0.011). Positive pAKT staining was associated with advanced
      stage disease (P=0.006). Other proteins were expressed only at low levels, and
      were not associated with any clinicopathological parameter or survival. None of
      the tumours were positive for EGFRvIII. In conclusion, our results indicate that
      tumours showing negative PTEN staining could represent a subgroup of ovarian
      carcinomas with a relatively favourable prognosis.

PMID- 18628767
TI  - Genomic adaptation: a fungal perspective.

PMID- 18628769
TI  - Carbon catabolite repression in bacteria: many ways to make the most out of
      nutrients.
AB  - Most bacteria can selectively use substrates from a mixture of different carbon
      sources. The presence of preferred carbon sources prevents the expression, and
      often also the activity, of catabolic systems that enable the use of secondary
      substrates. This regulation, called carbon catabolite repression (CCR), can be
      achieved by different regulatory mechanisms, including transcription activation
      and repression and control of translation by an RNA-binding protein, in different
      bacteria. Moreover, CCR regulates the expression of virulence factors in many
      pathogenic bacteria. In this Review, we discuss the most recent findings on the
      different mechanisms that have evolved to allow bacteria to use carbon sources in
      a hierarchical manner.

PMID- 18628771
TI  - What makes a virus a virus?

PMID- 18628772
TI  - How can we realize the promise of personalized antidepressant medicines?
AB  - Personalized medication that is based on pharmacogenetic data has long been
      expected to improve the efficacy of treatments for neurological and psychiatric
      disorders, including depression. However, the complexity of the regulation of
      gene transcription and its interactions with environmental factors means that
      straightforward translation of individual genetic information into tailored
      treatment is unlikely. Nevertheless, when data from genomics, proteomics,
      metabolomics, neuroimaging and neuroendocrinology are used in combination, they
      could lead to the development of effective personalized antidepressant treatment
      that is based on both genotypes and biomarkers. This process will require many
      further steps and collaboration between basic and clinical neuroscience.

PMID- 18628773
TI  - Stem cell niches as clinical targets: the future of anti-ischemic therapy?
AB  - This article provides context for the research presented by Napoli et al.,
      reported in this journal. Treatment strategies that target stem cell niches are
      promising avenues for stimulating inducible angiogenesis in many vascular
      diseases, such as diabetes mellitus and atherosclerosis. Here we discuss the
      study carried out by Napoli and colleagues--an analysis of the effects of
      parathyroid hormone on the vascular stem cell niche in peripheral ischemia.
      Napoli et al. demonstrate that parathyroid hormone administered in combination
      with granulocyte colony-stimulating factor induces angiogenesis in a hindlimb
      ischemia mouse model. This treatment seems to mobilize and localize endothelial
      cell progenitors specifically to ischemic vascular cell beds. We explore the
      mechanisms through which the multiple cells within the vascular niche respond to
      ischemia. The interaction between parathyroid hormone and granulocyte colony
      stimulating factor in humans is also discussed. Further assessment is needed to
      elucidate the factors involved in migration and differentiation of endothelial
      cell progenitors in ischemia-damaged tissues.

PMID- 18628774
TI  - Low-cost strategies to predict cardiovascular disease.
AB  - In this commentary, we discuss the potential utility of low-cost screening
      algorithms for the prediction of risk for cardiovascular disease. Strategies such
      as these might enhance screening and prevention programs but require validation.
      Testing the usefulness of low-cost prediction models in developing regions is the
      next logical step in carrying this concept forward.

PMID- 18628775
TI  - Dilated cardiomyopathy: an unusual complication of clozapine therapy.
AB  - BACKGROUND: A 42-year-old obese man presented with acute pulmonary edema. He had
      a history of chronic residual schizophrenia for which he had been taking
      clozapine for 7 years, but had no known prior cardiac disease. Echocardiography
      demonstrated severe biventricular systolic and diastolic dysfunction with severe
      left ventricular enlargement. Cardiac catheterization showed no coronary artery
      disease. INVESTIGATIONS: Physical examination, chest radiography,
      electrocardiography, transthoracic echocardiography, laboratory testing, viral
      serology, cardiac catheterization, coronary angiography and abdominal and renal
      ultrasonography. DIAGNOSIS: Clozapine-induced dilated cardiomyopathy. MANAGEMENT:
      Intravenous nesiritide, furosemide and morphine followed by oral heart-failure
      therapy comprising ramipril, metoprolol succinate, spironolactone, and
      furosemide. Clozapine therapy was withdrawn.

PMID- 18628776
TI  - Fibrates and future PPARalpha agonists in the treatment of cardiovascular
      disease.
AB  - Statins lower cardiovascular risk in patients with diabetes; however, as these
      patients are at higher risk than other cardiovascular patients, statins merely
      decrease coronary event rates to the level seen in untreated nondiabetic
      individuals at risk for cardiovascular disease, indicating the existence of
      substantial residual risk. One reasonable explanation resides in the fact that
      statins have only limited effectiveness on hypertriglyceridemia and low HDL
      cholesterol, and they do not normalize the LDL size-distribution pattern.
      Peroxisome proliferator-activated receptor (PPAR)alpha agonists, which include
      fibrates, normalize this atherogenic lipid profile, as well as several
      cardiovascular risk markers associated with the metabolic syndrome and type 2
      diabetes. In particular, hypertriglyceridemia and the ratio of small dense:large
      buoyant LDL particles are significantly improved. Outcome trials of PPARalpha
      agonists have demonstrated reductions in cardiovascular morbidity in patients
      with diabetes and in those with the metabolic syndrome; plaque progression is
      diminished, diabetic nephropathy and retinopathy are counteracted and amputation
      risk decreased. The combination of fibrates with statins improves overall
      lipoprotein profile further. PPARalpha agonists seem particularly indicated in
      patients with diabetes who have residual dyslipidemia (high triglyceride and/or
      low HDL) despite receiving statin therapy, and patients who are nondiabetic,
      overweight, insulin-resistant and who have hypertriglyceridemia and/or low HDL
      cholesterol and chronic inflammation.

PMID- 18628777
TI  - Multiple linear analysis methods for the quantification of irreversibly binding
      radiotracers.
AB  - Gjedde-Patlak graphical analysis (GPGA) has commonly been used to quantify the
      net accumulations (K(in)) of radioligands that bind or are taken up irreversibly.
      We suggest an alternative approach (MLAIR: multiple linear analysis for
      irreversible radiotracers) for the quantification of these types of tracers. Two
      multiple linear regression model equations were derived from differential
      equations of the two-tissue compartment model with irreversible binding. Multiple
      linear analysis for irreversible radiotracer 1 has a desirable feature for
      ordinary least square estimations because only the dependent variable C(T)(t) is
      noisy. Multiple linear analysis for irreversible radiotracer 2 provides K(in)
      from direct estimates of the coefficients of independent variables without the
      mediation of a division operation. During computer simulations, MLAIR1 provided
      less biased K(in) estimates than the other linear methods, but showed a high
      uncertainty level for noisy data, whereas MLAIR2 increased the robustness of
      estimation in terms of variability, but at the expense of increased bias. For
      real [(11)C]MeNTI positron emission tomography data, both methods showed good
      correlations, with parameters estimated using the standard nonlinear least
      squares method. Multiple linear analysis for irreversible radiotracer 2
      parametric images showed remarkable image quality as compared with GPGA images.
      It also showed markedly improved statistical power for voxelwise comparisons than
      GPGA. The two MLAIR approaches examined were found to have several advantages
      over the conventional GPGA method.

PMID- 18628778
TI  - A comprehensive analysis of gait impairment after experimental stroke and the
      therapeutic effect of environmental enrichment in rats.
AB  - Although gait changes are considered as reliable indices of stroke severity and
      efficacy of rehabilitative therapies in humans, data from animal models of focal
      ischemia are lacking. To determine the effect of stroke on gait function in adult
      rats with distal middle cerebral artery occlusion (MCAO), we assessed the
      longitudinal changes in gait using an automated computer-assisted gait analysis
      system. Four days after MCAO, intensity, maximal area of contact, and paw angle
      were significantly decreased in the affected forepaw whereas the double support
      time using ipsilateral paws increased. Relative print positions between the fore
      and hindpaws and limb coupling were also altered, suggesting that stroke affected
      sensorimotor status and reduced limb coordination. Except for paw angle, these
      impairments persisted for at least 5 weeks. However, unlike human stroke
      patients, stride length and stance were not affected in rats with MCAO.
      Environmental enrichment for 4 weeks improved paw contact area and relative print
      position of the affected limb and reduced double support time in ischemic rats
      compared with controls. Our results indicate that gait analysis provides great
      insight into various aspects of motor function changes in ischemic quadrupeds,
      and that environmental enrichment is beneficial in reducing a variety of
      poststroke gait impairments possibly through enhanced structural plasticity
      mechanisms within injured cortical neuronal networks underlying locomotor
      function.

PMID- 18628779
TI  - The role of Akt signaling in oxidative stress mediates NF-kappaB activation in
      mild transient focal cerebral ischemia.
AB  - Reactive oxygen species, derived from hypoxia and reoxygenation during transient
      focal cerebral ischemia (tFCI), are associated with the signaling pathway that
      leads to neuronal survival or death, depending on the severity and duration of
      the ischemic insult. The Akt survival signaling pathway is regulated by oxidative
      stress and is implicated in activation of nuclear factor-kappaB (NF-kappaB). Mild
      cerebral ischemia in mice was used to induce increased levels of Akt
      phosphorylation in the cortex and striatum. To clarify the role of Akt activation
      by NF-kappaB after tFCI, we injected the specific Akt inhibitor IV that inhibits
      Akt phosphorylation/activation. Inhibition of Akt phosphorylation induced
      decreases in sequential NF-kappaB signaling after 30 mins of tFCI at 1 h.
      Furthermore, the downstream survival signals of the Akt pathway were also
      decreased. Akt inhibitor IV increased ischemic infarct volume and apoptotic
      related DNA fragmentation. Superoxide production in the ischemic brains of mice
      pretreated with the Akt inhibitor was higher than in vehicle-treated mice. In
      addition, those pretreated mice showed a reduction of approximately 33% in
      copper/zinc-superoxide dismutase expression. We propose that Akt signaling exerts
      its neuroprotective role by NF-kappaB activation in oxidative cerebral ischemia
      in mice.

PMID- 18628780
TI  - Chronic riluzole treatment increases glucose metabolism in rat prefrontal cortex
      and hippocampus.
AB  - Riluzole is believed to modulate glutamatergic function by reducing glutamate
      release and facilitating astroglial uptake. We measured (13)C labeling in
      metabolites in prefrontal cortex and hippocampus during a 10 mins infusion of [1
      (13)C]glucose in urethane anesthetized rats treated with riluzole (21 days, 4
      mg/kg per day, i.p.) or saline. Total and (13)C concentrations of metabolites
      were determined in extracts using (1)H-[(13)C] NMR spectroscopy. In prefrontal
      cortex (P<0.05) and hippocampus (P<0.05) riluzole increased (13)C labeling over
      saline in glutamate-C4 (to 112% and 130%), GABA-C2 (to 142% and 171%), and
      glutamine-C4 (to 118% and 233%) without affecting total metabolite levels
      (P>0.2). Our findings indicate that contrary to expectation chronic riluzole
      enhanced glucose oxidative metabolism and glutamate/glutamine cycling.

PMID- 18628782
TI  - Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional
      explanation for delayed cerebral ischemia.
AB  - Patients with aneurysmal subarachnoid hemorrhage (SAH) who experience delayed
      cerebral ischemia (DCI) have an increased risk of poor outcome. Delayed cerebral
      ischemia is considered to be caused by vasospasm. However, not all patients with
      DCI have vasospasm. Inversely, not all patients with vasospasm develop clinical
      symptoms and signs of DCI. In the past, treatments aiming at vasospasm were not
      successful in preventing ischemia. The purpose of this review is to give an
      overview of clinical data showing that DCI cannot always be attributed to
      vasospasm, and to present an in-depth analysis of clinical and autopsy studies on
      the role of microthrombosis in the pathogenesis of DCI. Clinical studies show
      that DCI is associated with an activation of the coagulation cascade within a few
      days after SAH, preceding the time window during which vasospasm occurs.
      Furthermore, impaired fibrinolytic activity, and inflammatory and endothelium
      related processes, lead to the formation of microthrombi, which ultimately result
      in DCI. The presence of microthrombi is confirmed by autopsy studies. Insight in
      the pathophysiology of DCI is crucial for the development of effective therapies
      against this complication. Because multiple pathways are involved, future
      research should focus on drugs with pleiotropic effects.

PMID- 18628781
TI  - Genomic profiles of damage and protection in human intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) produces a high rate of death and disability. The
      molecular mechanisms of damage in perihematomal tissue in humans have not been
      systematically characterized. This study determines the gene expression profile
      and molecular networks that are induced in human perihematomal tissue through
      molecular analysis of tissue obtained from endoscopic clot evacuation.
      Differentially expressed genes and their cellular origin were confirmed in a
      mouse model of ICH. A total of 624 genes showed altered regulation in human ICH.
      Bioinformatic analysis shows that these genes form interconnected networks of
      proinflammatory, anti-inflammatory, and neuronal signaling cascades.
      Intracerebral hemorrhage evokes coordinated upregulation of proinflammatory
      signaling through specific cytokines and chemokines and their downstream
      molecular pathways. Anti-inflammatory networks are also induced by ICH, including
      annexins A1 and A2 and transforming growth factor beta (TGFbeta) and their
      intracellular cascades. Intracerebral hemorrhage downregulates many neuronal
      signaling systems, including the N-methyl-D-aspartic acid (NMDA) receptor complex
      and membrane ion channels. Select portions of these molecular networks were
      confirmed in the mouse, and the proteins in a subset of these networks localized
      to subsets of neurons, oligodendrocytes, or leukocytes. These inflammatory and
      anti-inflammatory networks interact at several key points in neutrophil
      signaling, apoptotic cell death, and protease responses, and indicate that
      secondary damage in ICH activates opposing molecular systems.

PMID- 18628783
TI  - Progesterone and its metabolite allopregnanolone differentially regulate
      hemostatic proteins after traumatic brain injury.
AB  - Our laboratory has shown in numerous experiments that the neurosteroids
      progesterone (PROG) and allopregnanolone (ALLO) improve molecular and functional
      outcomes after traumatic brain injury (TBI). As coagulopathy is an important
      contributor to the secondary destruction of nervous tissue, we hypothesized that
      PROG and ALLO administration may also have a beneficial effect on coagulation
      protein expression after TBI. Adult male Sprague-Dawley rats were given bilateral
      contusions of the medial frontal cortex followed by treatments with PROG (16
      mg/kg), ALLO (8 mg/kg), or vehicle (22.5% hydroxypropyl-beta-cyclodextrin).
      Controls received no injury or injections. Progesterone generally maintained
      procoagulant (thrombin, fibrinogen, and coagulation factor XIII), whereas ALLO
      increased anticoagulant protein expression (tissue-type plasminogen activator,
      tPA). In addition, PROG significantly increased the ratio of tPA bound to
      neuroserpin, a serine protease inhibitor that can reduce the activity of tPA. Our
      findings suggest that in a model of TBI, where blood loss may exacerbate injury,
      it may be preferable to treat patients with PROG, whereas it might be more
      appropriate to use ALLO as a treatment for thrombotic stroke, where a reduction
      in coagulation would be more beneficial.

PMID- 18628784
TI  - Cancer as an overhealing wound: an old hypothesis revisited.
AB  - What is the relationship between the wound-healing process and the development of
      cancer? Malignant tumours often develop at sites of chronic injury, and tissue
      injury has an important role in the pathogenesis of malignant disease, with
      chronic inflammation being the most important risk factor. The development and
      functional characterization of genetically modified mice that lack or overexpress
      genes that are involved in repair, combined with gene-expression analysis in
      wounds and tumours, have highlighted remarkable similarities between wound repair
      and cancer. However, a few crucial differences were also observed, which could
      account for the altered metabolism, impaired differentiation capacity and
      invasive growth of malignant tumours.

PMID- 18628785
TI  - Blebs lead the way: how to migrate without lamellipodia.
AB  - Blebs are spherical membrane protrusions that are produced by contractions of the
      actomyosin cortex. Blebs are often considered to be a hallmark of apoptosis;
      however, blebs are also frequently observed during cytokinesis and during
      migration in three-dimensional cultures and in vivo. For tumour cells and a
      number of embryonic cells, blebbing migration seems to be a common alternative to
      the more extensively studied lamellipodium-based motility. We argue that blebs
      should be promoted to a more prominent place in the world of cellular
      protrusions.

PMID- 18628787
TI  - Influence of MUC1 genetic variation on prostate cancer risk and survival.
AB  - Gene expression profiling has identified MUC1 as being significantly
      overexpressed in prostate cancer with poor clinical outcome after radical
      surgery, but the molecular mechanisms are still unclear. In this paper, we
      examined whether the genetic variation in MUC1 alters prostate cancer risk and
      progression. We identified five haplotype-tagging single-nucleotide polymorphisms
      that describe inherited genetic variation in and around MUC1. Individual single
      nucleotide polymorphisms as well as haplotypes were tested for association with
      prostate cancer risk and prognosis in 2760 cases and 1722 controls from the
      Swedish population. We found no association between any single-nucleotide
      polymorphism or haplotype in the MUC1 and risk of prostate cancer. Stratifying
      for disease severity or age of onset did not alter the results. Moreover, we
      observed no association with MUC1 variation and prostate cancer-specific
      survival. Common variants in MUC1 and the surrounding region are not associated
      with risk or prognosis of prostate cancer in Swedish men.

PMID- 18628786
TI  - Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with
      a novel AAAS mutation p.Leu430Phe.
AB  - The triple A syndrome is caused by autosomal recessively inherited mutations in
      the AAAS gene and is characterized by achalasia, alacrima and adrenal
      insufficiency as well as progressive neurological impairment. We report on a 14
      year-old girl with slowly progressive axonal motor neuropathy with conspicuous
      muscle wasting of hypothenars and calves as well as alacrima. The mutation
      analysis of the AAAS gene revealed a compound heterozygous mutation: a c.251G>A
      mutation in exon 2 that had been reported previously, and a novel c.1288C>T
      mutation in exon 14. At the transcriptional level, the c.251G>A transition
      results in an aberrant splicing and decay of this RNA strand so that the
      particular clinical picture results from the novel c.1288C>T, (p.Leu430Phe,
      L430F) mutation in a hemizygous form. With transfection experiments, we
      demonstrate that GFP-ALADIN(L430F) correctly localizes to nuclear pore complexes.
      Therefore, we conclude that this point mutation impairs ALADIN function at the
      nuclear pore.

PMID- 18628788
TI  - Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated
      full mutations.
AB  - Fragile X syndrome (FXS) is caused by the expansion of a CGG repeat in the 5'UTR
      of the FMR1 gene and the subsequent methylation of all CpG sites in the promoter
      region. We recently identified, in unrelated FXS families, two rare males with an
      unmethylated full mutation, that is, with an expanded CGG repeat (>200 triplets)
      lacking the typical CpG methylation in the FMR1 promoter. These individuals are
      not mentally retarded and do not appear to be mosaic for premutation or
      methylated full mutation alleles. We established lymphoblastoid and fibroblast
      cell lines that showed essentially normal levels of the FMR1-mRNA but reduced
      translational efficiency of the corresponding mRNA. Epigenetic analysis of the
      FMR1 gene demonstrated the lack of DNA methylation and a methylation pattern of
      lysines 4 and 27 on histone H3 similar to that of normal controls, in accordance
      with normal transcription levels and consistent with a euchromatic configuration.
      On the other hand, histone H3/H4 acetylation and lysine 9 methylation on histone
      H3 were similar to those of typical FXS cell lines, suggesting that these
      epigenetic changes are not sufficient for FMR1 gene inactivation. These findings
      demonstrate remarkable consistency and suggest a common genetic mechanism causing
      this rare FMR1 epigenotype. The discovery of such a mechanism may be important in
      view of therapeutic attempts to convert methylated into unmethylated full
      mutations, restoring the expression of the FMR1 gene.

PMID- 18628790
TI  - Array-based comparative genomic hybridization of mapped BAC DNA clones to screen
      for chromosome 14 copy number abnormalities in meningiomas.
AB  - Chromosome 14 loss in meningiomas are associated with more aggressive tumour
      behaviour. To date, no studies have been reported in which the entire chromosome
      14q of meningioma tumour cells has been studied by high-resolution array
      comparative genomic hybridization (a-CGH). Here, we used a high-resolution a-CGH
      to define the exact localization and extent of numerical changes of chromosome 14
      in meningioma patients. An array containing 807 bacterial artificial chromosome
      clones specific for chromosome 14q (average resolution of approximately 130 Kb)
      was constructed and applied to the study of 25 meningiomas in parallel to the
      confirmatory interphase fluorescence in situ hybridization (iFISH) analyses.
      Overall, abnormalities of chromosome 14q were detected in 10/25 cases (40%).
      Interestingly, in seven of these cases, loss of chromosome 14q32.3 was detected
      by iFISH and confirmed to correspond to monosomy 14 by a-CGH. In contrast,
      discrepant results were found between iFISH and a-CGH in the other three altered
      cases. In one patient, a diploid background was observed by iFISH, while monosomy
      14 was identified by a-CGH. In the remaining two cases, which showed gains of the
      IGH gene by iFISH, a-CGH did not detected copy number changes in one case showing
      a tetraploid karyotype, while in the other tumour, varying genetic imbalances
      along the long arm of chromosome 14 were detected. In summary, here, we report
      for the first time, the high-resolution a-CGH profiles of chromosome 14q in
      meningiomas, confirming that monosomy 14 is the most frequent alteration
      associated with this chromosome; other numerical abnormalities being only
      sporadically detected.

PMID- 18628789
TI  - Deciphering the genetics of hereditary non-syndromic colorectal cancer.
AB  - Previously we have localized to chromosome 3q21-q24, a predisposition locus for
      colorectal cancer (CRC), through a genome-wide linkage screen (GWLS) of 69
      families without familial adenomatous polyposis or hereditary non-polyposis CRC.
      To further investigate Mendelian susceptibility to CRC, we extended our screen to
      include a further GWLS of an additional 34 CRC families. We also searched for a
      disease gene at 3q21-q24 by linkage disequilibrium mapping in 620 familial CRC
      cases and 960 controls by genotyping 1676 tagging SNPs and sequencing 30
      candidate genes from the region. Linkage analysis was conducted using the
      Affymetrix 10K SNP array. Data from both GWLSs were pooled and multipoint linkage
      statistics computed. The maximum NPL score (3.01; P=0.0013) across all families
      was at 3q22, maximal evidence for linkage coming from families segregating rectal
      CRC. The same genomic position also yielded the highest multipoint heterogeneity
      LOD (HLOD) score under a dominant model (HLOD=2.79; P=0.00034), with an estimated
      43% of families linked. In the case-control analysis, the strongest association
      was obtained at rs698675 (P=0.0029), but this was not significant after adjusting
      for multiple testing. Analysis of candidate gene mapping to the region of maximal
      linkage on 3q22 failed to identify a causal mutation. There was no evidence for
      linkage to the previously reported 9q CRC locus (NPL=0.95, P=0.23;
      HLOD(dominant)=0.40, HLOD(recessive)=0.20). Our findings are consistent with the
      hypothesis that variation at 3q22 contributes to the risk of CRC, but this is
      unlikely to be mediated through a restricted set of alleles.

PMID- 18628792
TI  - Microbes orchestrate life on Earth.

PMID- 18628791
TI  - Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to
      cardiovascular disease events: the MORGAM Project.
AB  - Interleukin-18 (IL-18) is a key inflammatory molecule suspected of being involved
      in the etiology of cardiovascular diseases (CVD). Five single nucleotide
      polymorphisms (SNPs) capturing the common genetic variation of the IL-18 gene
      (tag SNPs) were genotyped in five European prospective CVD cohorts including 1933
      cases and 1938 non-cases as part of the MORGAM Project. Not a single SNP was
      found associated with CVD. However, a significant (P=0.002) gene-smoking
      interaction was observed. In smokers, the -105T allele was more frequent in cases
      than in non-cases (0.29 vs 0.25) and associated with an increased risk of disease
      (odds ratio (OR)=1.25 (1.07-1.45), P=0.005), whereas the inverse relationship
      tended to be observed in non-smokers (OR=0.90 (0.78-1.02), P=0.131). The gene
      smoking interaction was broadly homogenous across the cohorts and was also
      observed through haplotype analyses. In conclusion, using the concerted effort of
      several European prospective CVD cohorts, we are able to show that one IL-18 tag
      SNP interacts with smoking to modulate the risk of developing CVD.

PMID- 18628793
TI  - Characterization of exposures among cemented tungsten carbide workers. Part I:
      Size-fractionated exposures to airborne cobalt and tungsten particles.
AB  - As many as 30,000 workers in the United States of America are exposed to cemented
      tungsten carbides (CTC), alloys composed primarily of tungsten carbide and
      cobalt, which are used in cutting tools. Inhalation of cobalt-containing
      particles may be sufficient for the development of occupational asthma, whereas
      tungsten carbide particles in association with cobalt particles are associated
      with the development of hard metal disease (HMD) and lung cancer. Historical
      epidemiology and exposure studies of CTC workers often rely only on measures of
      total airborne cobalt mass concentration. In this study, we characterized cobalt-
      and tungsten-containing aerosols generated during the production of CTC with
      emphasis on (1) aerosol "total" mass (n=252 closed-face 37 mm cassette samples)
      and particle size-selective mass concentrations (n=108 eight-stage cascade
      impactor samples); (2) particle size distributions; and (3) comparison of
      exposures obtained using personal cassette and impactor samplers. Total cobalt
      and tungsten exposures were highest in work areas that handled powders (e.g.,
      powder mixing) and lowest in areas that handled finished product (e.g.,
      grinding). Inhalable, thoracic, and respirable cobalt and tungsten exposures were
      observed in all work areas, indicating potential for co-exposures to particles
      capable of getting deposited in the upper airways and alveolar region of the
      lung. Understanding the risk of CTC-induced adverse health effects may require
      two exposure regimes: one for asthma and the other for HMD and lung cancer. All
      sizes of cobalt-containing particles that deposit in the lung and airways have
      potential to cause asthma, thus a thoracic exposure metric is likely biologically
      appropriate. Cobalt-tungsten mixtures that deposit in the alveolar region of the
      lung may potentially cause HMD and lung cancer, thus a respirable exposure metric
      for both metals is likely biologically appropriate. By characterizing size
      selective and co-exposures as well as multiple exposure pathways, this series of
      papers offer an approach for developing biologically meaningful exposure metrics
      for use in epidemiology.

PMID- 18628794
TI  - Mean-square coherent light.
AB  - Mean-square coherent light is defined as light that is able to interfere with
      fringes of unit visibility when its electromagnetic field is multiplied by
      appropriate nonsingular deterministic Jones matrices. It includes light that
      satisfies the factorization condition at order one and partially polarized light
      that leads to interference fringes of unit visibility. A necessary and sufficient
      experimentally measurable condition to determine if two electromagnetic fields
      are mean-square coherent is established. Furthermore, different properties of
      partially polarized mean-square coherent light are discussed, such as its
      relation to the factorization condition and its evolution with propagation.

PMID- 18628795
TI  - Polarizing beam splitter of deep-etched triangular-groove fused-silica gratings.
AB  - We investigated the use of a deep-etched fused-silica grating with triangular
      shaped grooves as a highly efficient polarizing beam splitter (PBS). A triangular
      groove PBS grating is designed at a wavelength of 1550 nm to be used in optical
      communication. When it is illuminated in Littrow mounting, the transmitted TE-
      and TM-polarized waves are mainly diffracted in the minus-first and zeroth
      orders, respectively. The design condition is based on the average differences of
      the grating mode indices, which is verified by using rigorous coupled-wave
      analysis. The designed PBS grating is highly efficient over the C+L band range
      for both TE and TM polarizations (>97.68%). It is shown that such a triangular
      groove PBS grating can exhibit a higher diffraction efficiency, a larger
      extinction ratio, and less reflection loss than the binary-phase fused-silica PBS
      grating.

PMID- 18628796
TI  - Fractional decay of quantum dots in real photonic crystals.
AB  - We show that fractional decay may be observable in experiments using quantum dots
      and photonic crystals with parameters that are currently achievable. We focus on
      the case of inverse opal photonic crystals and locate the position in the crystal
      where the effect is most pronounced. Furthermore, we quantify the influence of
      absorptive loss and show that it is a limiting but not prohibitive effect.

PMID- 18628797
TI  - Continuously chirped fiber Bragg gratings by femtosecond laser structuring.
AB  - We report on what we believe to be the first successful inscription of
      continuously chirped fiber Bragg gratings (CCFBG) into a nonphotosensitive single
      mode fiber (SMF) with near-IR femtosecond laser pulses. The continuous chirp was
      achieved by inscribing into a bent fiber using a phase mask scanning technique.
      We fabricated a 20 mm long CCFBG with a bandwidth of 6 nm and a maximal
      reflectivity of 50%. The second-order dispersion of the CCFBG of up to 28 ps(2)
      was measured with spectral interferometry.

PMID- 18628798
TI  - Nonparaxial TM and TE beams in free space.
AB  - Expressions for the fields of TM and TE laser beams in free space that are
      rigorous solutions to Maxwell's equations are given in a closed form. The
      electric and the magnetic fields are both expressed in terms of nonparaxial
      elegant Laguerre-Gaussian beams that are exact solutions of the Helmholtz
      equation. These solutions involve well-known functions, such as spherical Bessel
      and associated Legendre functions. Radially and azimuthally polarized beams of
      arbitrary order are considered, and the lowest-order radially polarized beam
      (TM(01) beam) is investigated in detail.

PMID- 18628799
TI  - Wavelength modulation spectroscopy with a widely tunable InP-based 2.3 microm
      vertical-cavity surface-emitting laser.
AB  - We report on the successful application of recently developed 2.3 microm InP
      based vertical-cavity surface-emitting lasers with a buried tunnel junction in a
      wavelength modulation spectroscopy measurement for carbon monoxide (CO)
      detection. The electrically pumped devices operate at room temperature under cw
      operation with stable single-mode emission and should allow for parts in 10(6)
      (ppm) level resolution measurement of CO with a standard optical setup.

PMID- 18628800
TI  - Crystal quartz optical whispering-gallery resonators.
AB  - A quality factor exceeding 5x10(9) is obtained in whispering-gallery mode (WGM)
      resonators fabricated of crystalline quartz. We observe significant electrical
      tunability of WGMs in x-cut resonators and demonstrate an electro-optic modulator
      with a submegahertz passband at 12 GHz. We discuss other photonics applications
      of the crystal quartz WGM resonators in narrowband agile tunable filters, compact
      narrow linewidth lasers, and microwave and millimeter wave oscillators.

PMID- 18628801
TI  - Fabrication of 50 nm period gratings with multilevel interference lithography.
AB  - We have developed a multilevel interference lithography process to fabricate 50
      nm period gratings using light with a 351.1 nm wavelength. In this process
      multiple grating levels patterned by interference lithography are overlaid and
      spatial-phase aligned to a common reference grating using interferometry. Each
      grating level is patterned with offset phase shifts and etched into a single
      layer to achieve spatial-frequency multiplication. The effect of the multilayer
      periodic structure on interference lithography is examined to optimize the
      fabrication process. This process presents a general scheme for overlaying
      periodic structures and can be used to fabricate more complex periodic
      structures.

PMID- 18628802
TI  - Security enhancement of double-random phase encryption by amplitude modulation.
AB  - Conventional double-random phase encoding is vulnerable to a chosen or known
      plaintext attack owing to the linearity of the system. We introduce a technique
      to break down this linearity with an undercover amplitude modulation in the
      encryption scheme. As an additional key, this operation can significantly enhance
      the security of the system. A series of computer simulations have shown the
      effectiveness of this method and its resistance against the known plaintext
      attack. The design and parameter choice of the amplitude modulator is also
      discussed.

PMID- 18628803
TI  - Watt-level Er-doped and Er-Pr-codoped ZBLAN fiber amplifiers at the 2.7-2.8
      microm wavelength range.
AB  - Characteristics of diode-pumped Er-doped and Er-Pr-codoped ZBLAN fiber amplifiers
      were investigated at the 2.7-2.8 microm wavelength range. An amplified signal of
      4.6 W was obtained from the singly Er-doped amplifier for an input signal of 110
      mW, corresponding to a net gain of 16.2 dB. An amplified signal of 2.65 W was
      obtained from the Er-Pr-codoped amplifier for an input signal of 70 mW,
      corresponding to a net gain of 15.8 dB. It is found that the gain bandwidth of
      the singly Er-doped amplifier is much narrower than that of the Er-Pr-codoped
      amplifier. Small gain, no gain, or even a loss for shorter-wavelength signals
      propagating through the singly Er-doped amplifier should attribute for the large
      number residual populations in the lower laser level caused by the inefficient
      depopulation of the energy transfer upconversion processes.

PMID- 18628804
TI  - Simulation of polarization-sensitive optical coherence tomography images by a
      Monte Carlo method.
AB  - We introduce a new Monte Carlo (MC) method for simulating optical coherence
      tomography (OCT) images of complex multilayered turbid scattering media. We
      demonstrate, for the first time of our knowledge, the use of a MC technique to
      imitate two-dimensional polarization-sensitive OCT images with nonplanar
      boundaries of layers in the medium like a human skin. The simulation of polarized
      low-coherent optical radiation is based on the vector approach generalized from
      the iterative procedure of the solution of Bethe-Saltpeter equation. The
      performances of the developed method are demonstrated both for conventional and
      polarization-sensitive OCT modalities.

PMID- 18628805
TI  - Electromagnetic analysis of cylindrical cloaks of an arbitrary cross section.
AB  - We extend the design of radially symmetric invisibility cloaks through
      transformation optics as proposed by Pendry et al. [Science 312, 1780 (2006)] to
      coated cylinders of an arbitrary cross section. The validity of our Fourier-based
      approach is confirmed by both analytical and numerical results for a cloak
      displaying a non-convex cross section of varying thickness. In the former case,
      we evaluate the Green's function of a line source in the transformed coordinates.
      In the latter case, we implement a full-wave finite-element model for a
      cylindrical antenna radiating a p-polarized electric field in the presence of a F
      shaped lossy object surrounded by the cloak.

PMID- 18628806
TI  - Numerical study of exact Purcell factors in finite-size planar photonic crystal
      waveguides.
AB  - The waveguide-length sensitivity on modified spontaneous emission in finite-size
      planar photonic crystal (PC) waveguides is investigated by numerically computing
      the exact Purcell (enhanced emission) factor. An unusual dependence on the number
      of waveguide unit cells and on the waveguide facet truncation is found, allowing
      one to nanoengineer large Purcell factors in excess of several hundred. Besides
      having important applications for single-photon sources, these results offer
      physical insight into the nature of light-matter interactions in miniaturized
      finite-size PC waveguides, where periodic Bloch-wave analysis breaks down.

PMID- 18628807
TI  - Hybridization of electromagnetic numerical methods through the G-matrix
      algorithm.
AB  - For the sake of numerical performance, we hybridize two common approaches often
      used in electromagnetic computations, namely the finite-element method and the
      aperiodic Fourier modal method. To that end, we propose an extension of the
      classical S-matrix formalism to numerical situations, which requires handling
      different mathematical representations of the electromagnetic fields. As shown
      with a three-dimensional example, the proposed G-matrix formalism is stable and
      allows for an enhanced performance in terms of numerical accuracy and efficiency.

PMID- 18628808
TI  - Rapid-phase modulation of terahertz radiation for high-speed terahertz imaging
      and spectroscopy.
AB  - Rapid voltage-controlled phase modulation of cw terahertz (THz) radiation is
      demonstrated. By transmitting an infrared beam through a lithium niobate phase
      modulator the phase of the THz radiation, which is generated by the photomixing
      of two infrared beams, can be directly modulated through a 2pi phase shift. The
      100 kHz modulation rate that is demonstrated with this technique is approximately
      3 orders of magnitude faster than what can be achieved by mechanical scanning.

PMID- 18628809
TI  - Field-based angle-resolved light-scattering study of single live cells.
AB  - We perform field-based angle-resolved light-scattering measurements from single
      live cells. We use a laser interferometer to acquire phase and amplitude images
      of cells at the image plane. The angular scattering spectrum is calculated from
      the Fourier transform of the field transmitted through the cells. A concurrent 3D
      refractive index distribution of the same cells is measured using tomographic
      phase microscopy. By measuring transient increases in light scattering by single
      cells during exposure to acetic acid, we correlate the scattering properties of
      single cells with their refractive index distributions and show that results are
      in good agreement with a model based on the Born approximation.

PMID- 18628810
TI  - Modeling phase functions in biological tissue.
AB  - Scattering by randomly shaped particles is investigated for a better
      understanding of the optical properties of biological tissue and cell
      suspensions. After proposing the generation functions for the randomly shaped
      particles, the T-matrix method and appropriate effective size distribution are
      applied. The derived phase functions show good agreement with the experimental
      results. Implications for microscopic tissue diagnosis are discussed.

PMID- 18628811
TI  - Stable and spacing-adjustable multiwavelength Raman fiber laser based on mixed
      cascaded phosphosilicate fiber Raman linear cavity.
AB  - A novel multiwavelength Raman fiber laser based on the mixed-cascaded Stokes
      effects of phosphosilicate fiber is proposed and demonstrated experimentally. By
      using stimulated Raman scattering of both P(2)O(5) and SiO(2) along 1 km
      phosphosilicate fiber pumped with a 1064 nm double-clad fiber laser, the mixed
      cascaded Raman linear cavity is formed by a pair of fiber Bragg gratings at 1239
      nm, a polarization-maintaining fiber (PMF) Sagnac loop filter, and a conventional
      optical loop mirror. Up to 15-wavelength stable oscillations around 1320 nm are
      obtained with a wavelength spacing of 0.44 nm and power nonuniformity of less
      than 4 dB. By changing the length of the PMF in the Sagnac loop filter from 10 to
      5.5 m, the wavelength spacing is adjustable from 0.44 to 0.8 nm. The extinction
      ratio of the laser is more than 30 dB. Excellent stability is also observed with
      a peak power fluctuation of less than 0.8 dB in 1 h.

PMID- 18628812
TI  - Slow and stored light in an amplifying double-Lambda system.
AB  - We show analytically and numerically that a double-Lambda system, characterized
      by parametric amplification of cross-coupled probe and four-wave mixing pulses,
      is an excellent medium for producing both slow and stored light. Moreover, this
      system can compensate for the absorption and broadening processes that usually
      occur without destroying the coherent properties of the medium. The stored probe
      signal pulse is written by means of a simple Lambda system and is retrieved and
      amplified, at the same frequency, by a double-Lambda system that also produces a
      pulse at the four-wave mixing frequency.

PMID- 18628813
TI  - Passively mode-locked Yb:KLu(WO4)2 thin-disk oscillator operated in the positive
      and negative dispersion regime.
AB  - We demonstrate a passively mode-locked femtosecond Yb:KLu(WO(4))(2) thin-disk
      laser oscillator. Chirped-pulse operation in the positive dispersion regime as
      well as solitary operation have been realized, and the laser performance of both
      configurations are compared. In the solitary mode-locking regime the output power
      exceeds 25 W in a diffraction-limited beam, and pulse durations as short as 440
      fs at a 34.7 MHz repetition rate have been generated. For the first time we
      present a chirped-pulse operation of a thin-disk oscillator that yields a maximum
      average output power of 9.5 W with a Fourier limit of 450 fs.

PMID- 18628814
TI  - Sub-100 nm IR spectromicroscopy of living cells.
AB  - We have performed IR spectromicroscopy of cells immersed in liquid water, with a
      lateral resolution better than 100 nm. Here, we use the motion of an atomic force
      microscope tip, probing the local transient deformation induced by an IR pulsed
      laser tuned at a sample absorbing wavelength. By Fourier analysis of the
      vibration of the cantilever tip, we can discriminate frequencies that are
      characteristic of the object, thus eliminating the influence of the water
      absorption. This opens the door of chemical imaging of living species in vivo,
      with spatial resolution of the order of the size of cell components.

PMID- 18628815
TI  - Design of annular photonic crystal slabs.
AB  - We present the design of realistic annular photonic-crystal (APC) structures of
      finite thickness aiming to obtain a complete photonic bandgap (PBG). The APC is
      composed of dielectric rods and circular air holes in a triangular lattice such
      that each rod is centered within each hole. The optical and geometrical values of
      the structure are studied, and the interplay between various design parameters is
      highlighted. The coupled role of the inner-dielectric-rod radius, material types,
      and slab thickness is investigated. It is shown that the slab thickness is vital
      to obtain a complete photonic bandgap below the light line, and the specific
      value of the inner-dielectric-rod radius to sustain the maximum PBG if the hole
      radius is fixed at proper value is found.

PMID- 18628816
TI  - Axial coding in full-field microscopy using three-dimensional structured
      illumination implemented with no moving parts.
AB  - We report a simple optical setup to produce both axial and lateral structured
      illumination through a single objective lens. With a minimum of six full-field
      images obtained without moving either the sample or the microscope objective, 100
      nm diameter fluorescent beads can be localized axially with an accuracy of 50 nm
      in a 1.76-microm-thick layer. We show that this axial localization improvement
      can easily be combined with classical lateral structured illumination, so that
      lateral resolution enhancement by a factor of 2 is maintained.

PMID- 18628817
TI  - High-order dispersion-resulted tunable multiwavelength femtosecond laser.
AB  - Resonant dispersive waves generated by high-order dispersion in a Ti:sapphire
      mode-locked solitary laser are investigated and experiments are found to be in
      good agreement with theoretical analysis. Both theory and experiment show that
      the wavelength differences can be tuned in a large range via changing the cavity
      dispersion. This simple technique can be applied to the fields where tunable
      femtosecond pulses at multiple wavelengths are needed. The described mechanism
      may be applied in other systems where solitons are known to exist.

PMID- 18628818
TI  - Photonic crystal resonator integrated in a microfluidic system.
AB  - We report on a novel optofluidic system consisting of a silica-based 1D photonic
      crystal, integrated planar waveguides, and electrically insulated fluidic
      channels. An array of pillars in a microfluidic channel designed for
      electrochromatography is used as a resonator for on-column label-free refractive
      index detection. The resonator was fabricated in a silicon oxynitride platform,
      to support electro-osmotic flow, and operated at lambda=1.55 microm. Different
      aqueous solutions of ethanol with refractive indices ranging from n=1.3330 to
      1.3616 were pumped into the column/resonator, and the transmission spectra were
      recorded. Linear shifts of the resonant wavelengths yielded a maximum sensitivity
      of Deltalambda/Deltan=480 nm/RIU (refractive index unit), and a minimum
      difference of Deltan=0.007 RIU was measured.

PMID- 18628819
TI  - Extended focused imaging of a microparticle field with digital holographic
      microscopy.
AB  - We present a numerical technique for extended focused imaging and three
      dimensional analysis of a microparticle field observed in a digital holographic
      microscope working in transmission. The three-dimensional localization of objects
      is performed using the local focus plane determination method based on the
      integrated amplitude modulus. We apply the refocusing criterion locally for each
      pixel, using small overlapping windows, to obtain the depth map and a synthetic
      image in which all objects are refocused independent from their refocusing
      distance. A successful application of this technique in the analysis of the
      microgravity particle flow experiment is presented.

PMID- 18628820
TI  - Structured illumination in total internal reflection fluorescence microscopy
      using a spatial light modulator.
AB  - In wide-field fluorescence microscopy, illuminating the specimen with evanescent
      standing waves increases lateral resolution more than twofold. We report a
      versatile setup for standing-wave illumination in total internal reflection
      fluorescence microscopy. An adjustable diffraction grating written on a phase
      only spatial light modulator controls the illumination field. Selecting
      appropriate diffraction orders and displaying a sheared (tilted) diffraction
      grating allows one to tune the penetration depth in very fine steps. The setup
      achieves 91 nm lateral resolution for green emission.

PMID- 18628821
TI  - 1064 nm Nd:YVO4 laser intracavity pumped at 912 nm and sum-frequency mixing for
      an emission at 491 nm.
AB  - We present for the first time a Nd:YVO(4) laser emitting at 1064 nm intracavity
      pumped at 912 nm by a Nd:GdVO(4) laser. We carried out a model to design the
      system properly, and laser performance was experimentally investigated.
      Intracavity sum-frequency mixing at 912 and 1064 nm was then realized in a BiBO
      crystal to reach the blue range. We obtained a cw output power of 155 mW at 491
      nm with a pump laser diode emitting 20 W at 808 nm.

PMID- 18628822
TI  - Flexible Random Intercept Models for Binary Outcomes Using Mixtures of Normals.
AB  - Random intercept models for binary data are useful tools for addressing between
      subject heterogeneity. Unlike linear models, the non-linearity of link functions
      used for binary data force a distinction between marginal and conditional
      interpretations. This distinction is blurred in probit models with a normally
      distributed random intercept because the resulting model implies a probit
      marginal link as well. That is, this model is closed in the sense that the
      distribution associated with the marginal and conditional link functions and the
      random effect distribution are all of the same family. It is shown that the
      closure property is also attained when the distributions associated with the
      conditional and marginal link functions and the random effect distribution are
      mixtures of normals. The resulting flexible family of models is demonstrated to
      be related to several others present in the literature and can be used to
      synthesize several seemingly disparate modeling approaches. In addition, this
      family of models offers considerable computational benefits. A diverse series of
      examples is explored that illustrates the wide applicability of this approach.

PMID- 18628823
TI  - PKCepsilon stimulated arginine methylation of RIP140 for its nuclear-cytoplasmic
      export in adipocyte differentiation.
AB  - BACKGROUND: Receptor interacting protein 140 (RIP140) is a versatile
      transcriptional co-repressor that plays roles in diverse metabolic processes
      including fat accumulation in adipocytes. Previously we identified three
      methylated arginine residues in RIP140, which rendered its export to the
      cytoplasm; but it was unclear what triggered RIP140 arginine methylation.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we determined the activated
      PKCepsilon as the specific trigger for RIP140 arginine methylation and its
      subsequent export. We identified two PKCepsilon-phosphorylated residues of
      RIP140, Ser-102 and Ser-1003, which synergistically stimulated direct binding of
      RIP140 by 14-3-3 that recruited protein arginine methyl transferase 1 to
      methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1
      for nuclear export. As a result, the nuclear gene-repressive activity of RIP140
      was reduced. In RIP140 null adipocyte cultures, the defect in fat accumulation
      was effectively rescued by the phosphorylation-deficient mutant RIP140 that
      resided predominantly in the nucleus, but less so by the phospho-mimetic RIP140
      that was exported to the cytoplasm. CONCLUSIONS/SIGNIFICANCE: This study uncovers
      a novel means, via a cascade of protein modifications, to inactivate, or
      suppress, the nuclear action of an important transcription coregulator RIP140,
      and delineates the first specific phosphorylation-arginine methylation cascade
      that could alter protein subcellular distribution and biological activity.

PMID- 18628824
TI  - Targeted development of registries of biological parts.
AB  - BACKGROUND: The design and construction of novel biological systems by combining
      basic building blocks represents a dominant paradigm in synthetic biology.
      Creating and maintaining a database of these building blocks is a way to
      streamline the fabrication of complex constructs. The Registry of Standard
      Biological Parts (Registry) is the most advanced implementation of this idea.
      METHODS/PRINCIPAL FINDINGS: By analyzing inclusion relationships between the
      sequences of the Registry entries, we build a network that can be related to the
      Registry abstraction hierarchy. The distribution of entry reuse and complexity
      was extracted from this network. The collection of clones associated with the
      database entries was also analyzed. The plasmid inserts were amplified and
      sequenced. The sequences of 162 inserts could be confirmed experimentally but
      unexpected discrepancies have also been identified. CONCLUSIONS/SIGNIFICANCE:
      Organizational guidelines are proposed to help design and manage this new type of
      scientific resources. In particular, it appears necessary to compare the cost of
      ensuring the integrity of database entries and associated biological samples with
      their value to the users. The initial strategy that permits including any
      combination of parts irrespective of its potential value leads to an exponential
      and economically unsustainable growth that may be detrimental to the quality and
      long-term value of the resource to its users.

PMID- 18628825
TI  - Non-linear population firing rates and voltage sensitive dye signals in visual
      areas 17 and 18 to short duration stimuli.
AB  - Visual stimuli of short duration seem to persist longer after the stimulus offset
      than stimuli of longer duration. This visual persistence must have a
      physiological explanation. In ferrets exposed to stimuli of different durations
      we measured the relative changes in the membrane potentials with a voltage
      sensitive dye and the action potentials of populations of neurons in the upper
      layers of areas 17 and 18. For durations less than 100 ms, the timing and
      amplitude of the firing and membrane potentials showed several non-linear
      effects. The ON response became truncated, the OFF response progressively
      reduced, and the timing of the OFF responses progressively delayed the shorter
      the stimulus duration. The offset of the stimulus elicited a sudden and strong
      negativity in the time derivative of the dye signal. All these non-linearities
      could be explained by the stimulus offset inducing a sudden inhibition in layers
      II-III as indicated by the strongly negative time derivative of the dye signal.
      Despite the non-linear behavior of the layer II-III neurons the sum of the action
      potentials, integrated from the peak of the ON response to the peak of the OFF
      response, was almost linearly related to the stimulus duration.

PMID- 18628826
TI  - Potential effects of oilseed rape expressing oryzacystatin-1 (OC-1) and of
      purified insecticidal proteins on larvae of the solitary bee Osmia bicornis.
AB  - Despite their importance as pollinators in crops and wild plants, solitary bees
      have not previously been included in non-target testing of insect-resistant
      transgenic crop plants. Larvae of many solitary bees feed almost exclusively on
      pollen and thus could be highly exposed to transgene products expressed in the
      pollen. The potential effects of pollen from oilseed rape expressing the cysteine
      protease inhibitor oryzacystatin-1 (OC-1) were investigated on larvae of the
      solitary bee Osmia bicornis (= O. rufa). Furthermore, recombinant OC-1 (rOC-1),
      the Bt toxin Cry1Ab and the snowdrop lectin Galanthus nivalis agglutinin (GNA)
      were evaluated for effects on the life history parameters of this important
      pollinator. Pollen provisions from transgenic OC-1 oilseed rape did not affect
      overall development. Similarly, high doses of rOC-1 and Cry1Ab as well as a low
      dose of GNA failed to cause any significant effects. However, a high dose of GNA
      (0.1%) in the larval diet resulted in significantly increased development time
      and reduced efficiency in conversion of pollen food into larval body weight. Our
      results suggest that OC-1 and Cry1Ab expressing transgenic crops would pose a
      negligible risk for O. bicornis larvae, whereas GNA expressing plants could cause
      detrimental effects, but only if bees were exposed to high levels of the protein.
      The described bioassay with bee brood is not only suitable for early tier non
      target tests of transgenic plants, but also has broader applicability to other
      crop protection products.

PMID- 18628827
TI  - Genetic immunisation by liver stage antigen 3 protects chimpanzees against
      malaria despite low immune responses.
AB  - BACKGROUND: The true interest of genetic immunisation might have been hastily
      underestimated based on overall immunogenicity data in humans and lack of
      parallelism with other, more classical immunisation methods. PRINCIPAL FINDINGS:
      Using malaria Liver Stage Antigen-3 (LSA-3), we report that genetic immunization
      induces in chimpanzees, the closest relative of humans, immune responses which
      are as scarce as those reported using other DNA vaccines in humans, but which
      nonetheless confer strong, sterile and reproducible protection. The pattern was
      consistent in 3/4 immunized apes against two high dose sporozoite challenges
      performed as late as 98 and 238 days post-immunization and by a heterologous
      strain. CONCLUSIONS: These results should, in our opinion, lead to a revisiting
      of the value of this unusual means of immunisation, using as a model a disease,
      malaria, in which virulent challenges of volunteers are ethically acceptable.

PMID- 18628828
TI  - Modelling the epidemiological impact of intermittent preventive treatment against
      malaria in infants.
AB  - BACKGROUND: Trials of intermittent preventive treatment against malaria in
      infants (IPTi) using sulphadoxine-pyrimethamine (SP) have shown a positive,
      albeit variable, protective efficacy against clinical malaria episodes. The
      impact of IPTi in different epidemiological settings and over time is unknown and
      predictions are hampered by the lack of knowledge about how IPTi works. We
      investigated mechanisms proposed for the action of IPTi and made predictions of
      the likely impact on morbidity and mortality. METHODS/PRINCIPAL FINDINGS: We used
      a comprehensive, individual-based, stochastic model of malaria epidemiology to
      simulate recently published trials of IPTi using SP with site-specific
      characteristics as inputs. This baseline model was then modified to represent
      hypotheses concerning the duration of action of SP, the temporal pattern of
      fevers caused by individual infections, potential benefits of avoiding fevers on
      immunity and the effect of sub-therapeutic levels of SP on parasite dynamics. The
      baseline model reproduced the pattern of results reasonably well. None of the
      models based on alternative hypotheses improved the fit between the model
      predictions and observed data. Predictions suggest that IPTi would have a
      beneficial effect across a range of transmission intensities. IPTi was predicted
      to avert a greater number of episodes where IPTi coverage was higher, the health
      system treatment coverage lower, and for drugs which were more efficacious and
      had longer prophylactic periods. The predicted cumulative benefits were
      proportionately slightly greater for severe malaria episodes and malaria
      attributable mortality than for acute episodes in the settings modelled. Modest
      increased susceptibility was predicted between doses and following the last dose,
      but these were outweighed by the cumulative benefits. The impact on transmission
      intensity was negligible. CONCLUSIONS: The pattern of trial results can be
      accounted for by differences between the trial sites together with known features
      of malaria epidemiology and the action of SP. Predictions suggest that IPTi would
      have a beneficial impact across a variety of epidemiological settings.

PMID- 18628829
TI  - Interferon-gamma release assay for the diagnosis of latent TB infection--analysis
      of discordant results, when compared to the tuberculin skin test.
AB  - BACKGROUND: With the Interferon-gamma release assays (IGRA) a new method for the
      diagnosis of latent tuberculosis infections (LTBI) is available. Due to the lack
      of a gold standard for the diagnosis of LTBI, the IGRA is compared to the Mantoux
      Tuberculin Skin Test (TST), which yields discordant results in varying numbers.
      Therefore we assessed to which extent discordant results can be explained by
      potential risk factors such as age, BCG vaccination and migration. METHODS AND
      FINDINGS: In this pooled analysis, two German studies evaluating the Quantiferon
      Gold In-Tube test (QFT) by comparison with the TST (RT23 of SSI) were combined
      and logistic regressions for potential risk factors for TST+/QFT- as well as THT
      /QFT+ discordance were calculated. The analysis comprises 1,033 participants.
      Discordant results were observed in 15.4%, most of them being TST+/QFT-
      combinations. BCG vaccination or migration explained 85.1% of all TST+/QFT-
      discordance. Age explained 49.1% of all TST-/QFT+ discordance. Agreement between
      the two tests was 95.6% in German-born persons younger than 40 years and not BCG
      vaccinated. CONCLUSIONS: After adjustment for potential risk factors for positive
      or negative TST results, agreement of QFT and TST is excellent with little
      potential that the TST is more likely to detect old infections than the QFT. In
      surveillance programs for LTBI in high-income, low TB incidence countries like
      Germany the QFT is especially suited for persons with BCG vaccination or migrants
      due to better specificity and in older persons due to its superior sensitivity.

PMID- 18628830
TI  - Female dominance over males in primates: self-organisation and sexual dimorphism.
AB  - The processes that underlie the formation of the dominance hierarchy in a group
      are since long under debate. Models of self-organisation suggest that dominance
      hierarchies develop by the self-reinforcing effects of winning and losing fights
      (the so-called winner-loser effect), but according to 'the prior attribute
      hypothesis', dominance hierarchies develop from pre-existing individual
      differences, such as in body mass. In the present paper, we investigate the
      relevance of each of these two theories for the degree of female dominance over
      males. We investigate this in a correlative study in which we compare female
      dominance between groups of 22 species throughout the primate order. In our study
      female dominance may range from 0 (no female dominance) to 1 (complete female
      dominance). As regards 'the prior attribute hypothesis', we expected a negative
      correlation between female dominance over males and species-specific sexual
      dimorphism in body mass. However, to our surprise we found none (we use the
      method of independent contrasts). Instead, we confirm the self-organisation
      hypothesis: our model based on the winner-loser effect predicts that female
      dominance over males increases with the percentage of males in the group. We
      confirm this pattern at several levels in empirical data (among groups of a
      single species and between species of the same genus and of different ones).
      Since the winner-loser effect has been shown to work in many taxa including
      humans, these results may have broad implications.

PMID- 18628831
TI  - Genomic instability is associated with natural life span variation in
      Saccharomyces cerevisiae.
AB  - Increasing genomic instability is associated with aging in eukaryotes, but the
      connection between genomic instability and natural variation in life span is
      unknown. We have quantified chronological life span and loss-of-heterozygosity
      (LOH) in 11 natural isolates of Saccharomyces cerevisiae. We show that genomic
      instability increases and mitotic asymmetry breaks down during chronological
      aging. The age-dependent increase of genomic instability generally lags behind
      the drop of viability and this delay accounts for approximately 50% of the
      observed natural variation of replicative life span in these yeast isolates. We
      conclude that the abilities of yeast strains to tolerate genomic instability co
      vary with their replicative life spans. To the best of our knowledge, this is the
      first quantitative evidence that demonstrates a link between genomic instability
      and natural variation in life span.

PMID- 18628836
TI  - Meeting review: plant bioinformatics at the NSF and NPGI (PAMGX satellite)
      meetings.
AB  - This brief meeting review summarizes the recommendations of NSF and NPGI funded
      bioinformaticians concerning the future requirements for plant bioinformatics
      systems and databases.

PMID- 18628834
TI  - Featured organism: Schizosaccharomyces pombe, the fission yeast.
AB  - Schizosaccharomyces pombe, the fission yeast, has long been a crucial model for
      the study of the eukaryote cell cycle. We take a look at this important yeast,
      whose genome has recently been completed, featuring comments from Valerie Wood,
      Jurg Bahler, Ramsay McFarlane, Susan Forsburg, Iain Hagan and Paul Nurse on the
      implications of having the complete sequence and future prospects for pombe
      genomics.

PMID- 18628832
TI  - Virus-like particles of SARS-like coronavirus formed by membrane proteins from
      different origins demonstrate stimulating activity in human dendritic cells.
AB  - The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the
      current study, two recombinant baculovirus were generated to express the spike
      (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the
      envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of
      insect cells with these two recombinant baculoviruses led to self-assembly of
      virus-like particles (BVLPs) as demonstrated by electron microscopy.
      Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot
      and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86,
      CD83, and enhanced the secretion of IL-6, IL-10 and TNF-alpha in immature
      dendritic cells (DCs). Immune responses were compared in immature DCs inoculated
      with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs
      showed a stronger ability to stimulate DCs in terms of cytokine induction as
      evidenced by 2 to 6 fold higher production of IL-6 and TNF-alpha. Further study
      indicated that IFN-gamma+ and IL-4+ populations in CD4+ T cells increased upon co
      cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed
      difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very
      likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more
      vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in
      mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by
      membrane proteins of different origins, one from SL-CoV isolated from bats (BS)
      and the other two from human SARS-CoV (E and M), activated immature DCs and
      enhanced the expression of co-stimulatory molecules and the secretion of
      cytokines. Finding in this study may provide important information for vaccine
      development as well as for understanding the pathogenesis of SARS-like CoV.

PMID- 18628837
TI  - Advanced mass spectrometric methods for the rapid and quantitative
      characterization of proteomes.
AB  - Progress is reviewed towards the development of a global strategy that aims to
      extend the sensitivity, dynamic range, comprehensiveness and throughput of
      proteomic measurements based upon the use of high performance separations and
      mass spectrometry. The approach uses high accuracy mass measurements from Fourier
      transform ion cyclotron resonance mass spectrometry (FTICR) to validate peptide
      'accurate mass tags' (AMTs) produced by global protein enzymatic digestions for a
      specific organism, tissue or cell type from 'potential mass tags' tentatively
      identified using conventional tandem mass spectrometry (MS/MS). This provides the
      basis for subsequent measurements without the need for MS/ MS. High resolution
      capillary liquid chromatography separations combined with high sensitivity, and
      high resolution accurate FTICR measurements are shown to be capable of
      characterizing peptide mixtures of more than 10(5) components. The strategy has
      been initially demonstrated using the microorganisms Saccharomyces cerevisiae and
      Deinococcus radiodurans. Advantages of the approach include the high confidence
      of protein identification, its broad proteome coverage, high sensitivity, and the
      capability for stableisotope labeling methods for precise relative protein
      abundance measurements. ABBREVIATIONS: LC, liquid chromatography; FTICR, Fourier
      transform ion cyclotron resonance; AMT, accurate mass tag; PMT, potential mass
      tag; MMA, mass measurement accuracy; MS, mass spectrometry; MS/MS, tandem mass
      spectrometry; ppm, parts per million.

PMID- 18628838
TI  - Development and utilization of tomato microarrays for the Solanaceae.

PMID- 18628840
TI  - Meeting highlights: plant, animal and microbe genomes X.

PMID- 18628839
TI  - Computational comparative genomics of eu- and prokaryotes.

PMID- 18628841
TI  - The patentability of biomolecules - does online bioinformatics compromise
      novelty?
AB  - Researchers are becoming increasingly concerned that the confidentiality of their
      novel biomolecule sequences is being jeopardised, particularly when these
      sequences are either submitted to sequence databases or uploaded as query terms
      onto internet-based bioinformatic software suites. The researcher's fears stem
      from the fact that the actual uploading of their sequences acts as a novelty
      destroying prior disclosure or publication, and that this may subsequently
      preclude valid patent protection for the sequences. This article addresses the
      key issues involved in the analyses of biomolecules, highlighting potential risks
      taken by many researchers in regard to patent protection and suggests possible
      ways in which these risks may be mitigated.

PMID- 18628842
TI  - The Plant Ontology Consortium and plant ontologies.
AB  - The goal of the Plant Ontology Consortium is to produce structured controlled
      vocabularies, arranged in ontologies, that can be applied to plant-based database
      information even as knowledge of the biology of the relevant plant taxa (e.g.
      development, anatomy, morphology, genomics, proteomics) is accumulating and
      changing. The collaborators of the Plant Ontology Consortium (POC) represent a
      number of core participant database groups. The Plant Ontology Consortium is
      expanding the paradigm of the Gene Ontology Consortium
      (http://www.geneontology.org). Various trait ontologies (agronomic traits, mutant
      phenotypes, phenotypes, traits, and QTL) and plant ontologies (plant development,
      anatomy [incl. morphology]) for several taxa (Arabidopsis, maize/corn/Zea mays
      and rice/Oryza) are under development. The products of the Plant Ontology
      Consortium will be open-source.

PMID- 18628843
TI  - ISYS (Integrated SYStem): a platform for integrating heterogeneous bioinformatic
      resources.

PMID- 18628844
TI  - The REGIA database (RegiaDB): status, limitations and future developments.

PMID- 18628846
TI  - Meeting Review: Joint Prince Henry's Institute of Medical Research and Monash
      Institute of Reproduction and Development Symposium - Reproductive Genomics.

PMID- 18628845
TI  - StressDB: a locally installable web-based relational microarray database designed
      for small user communities.
AB  - We have built a microarray database, StressDB, for management of microarray data
      from our studies on stress-modulated genes in Arabidopsis. StressDB provides
      small user groups with a locally installable web-based relational microarray
      database. It has a simple and intuitive architecture and has been designed for
      cDNA microarray technology users. StressDB uses Windows 2000 as the centralized
      database server with Oracle 8i as the relational database management system. It
      allows users to manage microarray data and data-related biological information
      over the Internet using a web browser. The source-code is currently available on
      request from the authors and will soon be made freely available for downloading
      from our website athttp://arastressdb.cac.psu.edu.

PMID- 18628847
TI  - Differentiation of plant cells during symbiotic nitrogen fixation.
AB  - Nitrogen-fixing symbioses between legumes and bacteria of the family Rhizobiaceae
      involve differentiation of both plant and bacterial cells. Differentiation of
      plant root cells is required to build an organ, the nodule, which can feed and
      accommodate a large population of bacteria under conditions conducive to nitrogen
      fixation. An efficient vascular system is built to connect the nodule to the
      root, which delivers sugars and other nutrients to the nodule and removes the
      products of nitrogen fixation for use in the rest of the plant. Cells in the
      outer cortex differentiate to form a barrier to oxygen diffusion into nodules,
      which helps to produce the micro-aerobic environment necessary for bacterial
      nitrogenase activity. Cells of the central, infected zone of nodules undergo
      multiple rounds of endoreduplication, which may be necessary for colonisation by
      rhizobia and may enable enlargement and greater metabolic activity of these
      cells. Infected cells of the nodule contain rhizobia within a unique plant
      membrane called the peribacteroid or symbiosome membrane, which separates the
      bacteria from the host cell cytoplasm and mediates nutrient and signal exchanges
      between the partners. Rhizobia also undergo differentiation during nodule
      development. Not surprisingly, perhaps, differentiation of each partner is
      dependent upon interactions with the other. High-throughput methods to assay gene
      transcripts, proteins, and metabolites are now being used to explore further the
      different aspects of plant and bacterial differentiation. In this review, we
      highlight recent advances in our understanding of plant cell differentiation
      during nodulation that have been made, at least in part, using high-throughput
      methods.

PMID- 18628849
TI  - REGIA, an EU project on functional genomics of transcription factors from
      Arabidopsis Thaliana.
AB  - Transcription factors (TFs) are regulatory proteins that have played a pivotal
      role in the evolution of eukaryotes and that also have great biotechnological
      potential. REGIA (REgulatory Gene Initiative in Arabidopsis) is an EU-funded
      project involving 29 European laboratories with the objective of determining the
      function of virtually all transcription factors from the model plant, Arabidopsis
      thaliana. REGIA involves: 1. the definition of TF gene expression patterns in
      Arabidopsis; 2. the identification of mutations at TF loci; 3. the ectopic
      expression of TFs (or derivatives) in Arabidopsis and in crop plants; 4.
      phenotypic analysis of the mutants and mis-expression lines, including both RNA
      and metabolic profiling; 5. the systematic analysis of interactions between TFs;
      and 6. the generation of a bioinformatics infrastructure to access and integrate
      all this information. We expect that this programme will establish the full
      biotechnological potential of plant TFs, and provide insights into hierarchies,
      redundancies, and interdependencies, and their evolution. The project involves
      the preparation of both a TF gene array for expression analysis and a normalised
      full length open reading frame (ORF) library of TFs in a yeast two hybrid vector;
      the applications of these resources should extend beyond the scope of this
      programme.

PMID- 18628851
TI  - Mimotopes and proteome analyses using human genomic and cDNA epitope phage
      display.
AB  - In the post-genomic era, validation of candidate gene targets frequently requires
      proteinbased strategies. Phage display is a powerful tool to define protein
      protein interactions by generating peptide binders against target antigens.
      Epitope phage display libraries have the potential to enrich coding exon
      sequences from human genomic loci. We evaluated genomic and cDNA phage display
      strategies to identify genes in the 5q31 Interleukin gene cluster and to enrich
      cell surface receptor tyrosine kinase genes from a breast cancer cDNA library. A
      genomic display library containing 2 x 106 clones with exon-sized inserts was
      selected with antibodies specific for human Interleukin-4 (IL-4) and Interleukin
      13. The library was enriched significantly after two selection rounds and DNA
      sequencing revealed unique clones. One clone matched a cognate IL-4 epitope;
      however, the majority of clone insert sequences corresponded to E. coli genomic
      DNA. These bacterial sequences act as 'mimotopes' (mimetic sequences of the true
      epitope), correspond to open reading frames, generate displayed peptides, and
      compete for binding during phage selection. The specificity of these mimotopes
      for IL-4 was confirmed by competition ELISA. Other E. coli mimotopes were
      generated using additional antibodies. Mimotopes for a receptor tyrosine kinase
      gene were also selected using a breast cancer SKBR-3 cDNA phage display library,
      screened against an anti-erbB2 monoclonal antibody. Identification of mimotopes
      in genomic and cDNA phage libraries is essential for phage display-based protein
      validation assays and two-hybrid phage approaches that examine protein-protein
      interactions. The predominance of E. coli mimotopes suggests that the E. coli
      genome may be useful to generate peptide diversity biased towards protein coding
      sequences.

PMID- 18628852
TI  - Meeting review: 2002 O'Reilly Bioinformatics Technology Conference.
AB  - At the end of January I travelled to the States to speak at and attend the first
      O'Reilly Bioinformatics Technology Conference. It was a large, well-organized and
      diverse meeting with an interesting history. Although the meeting was not a
      typical academic conference, its style will, I am sure, become more typical of
      meetings in both biological and computational sciences.Speakers at the event
      included prominent bioinformatics researchers such as Ewan Birney, Terry
      Gaasterland and Lincoln Stein; authors and leaders in the open source programming
      community like Damian Conway and Nat Torkington; and representatives from several
      publishing companies including the Nature Publishing Group, Current Science Group
      and the President of O'Reilly himself, Tim O'Reilly. There were presentations,
      tutorials, debates, quizzes and even a 'jam session' for musical
      bioinformaticists.

PMID- 18628853
TI  - Upstream - news in genomics.
AB  - In recent months a bumper crop of genomes has been completed, including the
      fission yeast (Schizosaccharomyces pombe) and rice (Oryza sativa). Two large
      scale studies of Saccharomyces cerevisiae protein complexes provided a picture of
      the eukaryotic proteome as a network of complexes. Amongst the other stories of
      interest was a demonstration that proteomic analysis of blood samples can be used
      to detect ovarian cancer, perhaps even as early as stage I.

PMID- 18628854
TI  - Meeting review: Bioinformatics and Medicine - from molecules to humans, virtual
      and real.
AB  - The Industrialization Workshop Series aims to promote and discuss integration,
      automation, simulation, quality, availability and standards in the high
      throughput life sciences. The main issues addressed being the transformation of
      bioinformatics and bioinformaticsbased drug design into a robust discipline in
      industry, the government, research institutes and academia. The latest workshop
      emphasized the influence of the post-genomic era on medicine and healthcare with
      reference to advanced biological systems modeling and simulation, protein
      structure research, protein-protein interactions, metabolism and physiology.
      Speakers included Michael Ashburner, Kenneth Buetow, Francois Cambien, Cyrus
      Chothia, Jean Garnier, Francois Iris, Matthias Mann, Maya Natarajan, Peter Murray
      Rust, Richard Mushlin, Barry Robson, David Rubin, Kosta Steliou, John Todd, Janet
      Thornton, Pim van der Eijk, Michael Vieth and Richard Ward.

PMID- 18628855
TI  - Studying the functional genomics of stress responses in loblolly pine with the
      Expresso microarray experiment management system.
AB  - Conception, design, and implementation of cDNA microarray experiments present a
      variety of bioinformatics challenges for biologists and computational scientists.
      The multiple stages of data acquisition and analysis have motivated the design of
      Expresso, a system for microarray experiment management. Salient aspects of
      Expresso include support for clone replication and randomized placement;
      automatic gridding, extraction of expression data from each spot, and quality
      monitoring; flexible methods of combining data from individual spots into
      information about clones and functional categories; and the use of inductive
      logic programming for higher-level data analysis and mining. The development of
      Expresso is occurring in parallel with several generations of microarray
      experiments aimed at elucidating genomic responses to drought stress in loblolly
      pine seedlings. The current experimental design incorporates 384 pine cDNAs
      replicated and randomly placed in two specific microarray layouts. We describe
      the design of Expresso as well as results of analysis with Expresso that suggest
      the importance of molecular chaperones and membrane transport proteins in
      mechanisms conferring successful adaptation to long-term drought stress.

PMID- 18628856
TI  - Meeting review: Epigenetics in Development and Disease.
AB  - The 2002 Keystone symposia held in Taos, New Mexico (21-26 February) saw the
      convergence of two related fields; Epigenetics in Development and Disease, and
      RNA Interference, Cosuppression and Related Phenomena. The meeting highlights
      presented here concentrate upon the sessions within the Epigenetics in
      Development and Disease meeting, although there were joint sessions which will
      also be discussed. Of course epigenetic regulation is not restricted to the
      vertebrates but I have chosen, rightly or wrongly, to limit the highlights to
      those concerning vertebrates.

PMID- 18628857
TI  - Overlapping antisense transcription in the human genome.
AB  - Accumulating evidence indicates an important role for non-coding RNA molecules in
      eukaryotic cell regulation. A small number of coding and non-coding overlapping
      antisense transcripts (OATs) in eukaryotes have been reported, some of which
      regulate expression of the corresponding sense transcript. The prevalence of this
      phenomenon is unknown, but there may be an enrichment of such transcripts at
      imprinted gene loci. Taking a bioinformatics approach, we systematically searched
      a human mRNA database (RefSeq) for complementary regions that might facilitate
      pairing with other transcripts. We report 56 pairs of overlapping transcripts, in
      which each member of the pair is transcribed from the same locus. This allows us
      to make an estimate of 1000 for the minimum number of such transcript pairs in
      the entire human genome. This is a surprisingly large number of overlapping gene
      pairs and, clearly, some of the overlaps may not be functionally significant.
      Nonetheless, this may indicate an important general role for overlapping
      antisense control in gene regulation. EST databases were also investigated in
      order to address the prevalence of cases of imprinted genes with associated non
      coding overlapping, antisense transcripts. However, EST databases were found to
      be completely inappropriate for this purpose.

PMID- 18628858
TI  - Website review: how to get the best from fission yeast genome data.
AB  - Researchers are increasingly depending on various centralized resources to access
      the vast amount of information reported in the literature and generated by
      systematic sequencing and functional genomics projects. Biological databases have
      become everyday working tools for many researchers. This dependency goes both
      ways in that the databases require continuous feedback from the research
      community to maintain accurate, reliable, and upto- date information. The fission
      yeast Schizosaccharomyces pombe has recently been sequenced, setting the stage
      for the post-genome era of this popular model organism. Here, we provide an
      overview of relevant databases available, or being developed, together with a
      compilation of Internet resources containing useful information and tools for
      fission yeast.

PMID- 18628860
TI  - Proposal for a standard representation of two-dimensional gel electrophoresis
      data.
AB  - The global analysis of proteins is now feasible due to improvements in techniques
      such as two-dimensional gel electrophoresis (2-DE), mass spectrometry, yeast two
      hybrid systems and the development of bioinformatics applications. The
      experiments form the basis of proteomics, and present significant challenges in
      data analysis, storage and querying. We argue that a standard format for proteome
      data is required to enable the storage, exchange and subsequent re-analysis of
      large datasets. We describe the criteria that must be met for the development of
      a standard for proteomics. We have developed a model to represent data from 2-DE
      experiments, including difference gel electrophoresis along with image analysis
      and statistical analysis across multiple gels. This part of proteomics analysis
      is not represented in current proposals for proteomics standards. We are working
      with the Proteomics Standards Initiative to develop a model encompassing
      biological sample origin, experimental protocols, a number of separation
      techniques and mass spectrometry. The standard format will facilitate the
      development of central repositories of data, enabling results to be verified or
      re-analysed, and the correlation of results produced by different research groups
      using a variety of laboratory techniques.

PMID- 18628861
TI  - Worldwide genomic resources for non-model fish species.

PMID- 18628864
TI  - The low down on e-science and grids for biology.
AB  - The Grid is touted as a next generation Internet/Web, designed primarily to
      support e-Science. I hope to shed some light on what the Grid is, its purpose,
      and its potential impact on scientific practice in biology. The key message is
      that biologists are already primarily working in a manner that the Grid is
      intended to support. However, to ensure that the Grid's good intentions are
      appropriate and fulfilled in practice, biologists must become engaged in the
      process of its development.

PMID- 18628865
TI  - Meeting highlights: joint Cold Spring Harbor Laboratory and Wellcome Trust
      conference - genome informatics.

PMID- 18628866
TI  - Upstream - news in genomics.
AB  - Since our last issue, several important genomes have been completely or 'almost
      completely' sequenced. The debate over the number of human genes has flared up
      once more, with one computational and one experimental study into the annotation
      of the human genome. The mouse genome project has a clone fingerprint map to aid
      their sequencing effort. The SAGE technique has been applied to Drosophila and
      the US National Science Foundation announced increased spending on plant genome
      research.

PMID- 18628868
TI  - The interaction between endopolygalacturonase from Fusarium moniliforme and PGIP
      from Phaseolus Vulgaris studied by surface plasmon resonance and mass
      spectrometry.
AB  - A combination of surface plasmon resonance (SPR) and matrix-assisted laser
      desorptionionization- time-of-flight mass spectrometry (MALDI-TOF-MS) was used to
      study the interaction between endopolygalacturonase (PG) from Fusarium
      moniliforme and a polygalacturonase-inhibiting protein (PGIP) from Phaseolus
      vulgaris. PG hydrolyses the homogalacturonan of the plant cell wall and is
      considered an important pathogenicity factor of many fungi. PGIP is a specific
      inhibitor of fungal PGs and is thought to be involved in plant defence against
      phytopathogenic fungi. SPR was used either to study the effect of the PG
      glycosylation on the formation of the complex with PGIP, and as a sensitive
      affinity capture of an interacting peptide from a mixture of PG fragments
      obtained by limited proteolysis. Mass spectrometry allowed to characterise the
      interacting peptide eluted from the sensor surface.

PMID- 18628869
TI  - C(2)M: configurable chemical middleware.
AB  - One of the vexing problems that besets concurrent use of multiple, heterogeneous
      resources is format multiplicity. C(2)M aims to equip scientists with a wrapper
      generator on their desktop. The wrapper generator can build wrappers, or
      converters that can convert data from or into different formats, from a high
      level description of the formats. The language in which such a high-level
      description is expressed is easy enough for scientists to be able to write format
      descriptions at minimal cost. In C(2)M, wrappers and documentation for human
      reading are automatically obtained from the same user-supplied specifications.
      Initial experiments demonstrate that the idea can, indeed, lead to the advent of
      usergoverned wrapper generators. Future research will consolidate the code and
      extend the approach to a realistic variety of formats.

PMID- 18628870
TI  - Pathway databases.

PMID- 18628871
TI  - TEMBLOR - Perspectives of EBI Database Services.

PMID- 18628873
TI  - Website update: a new graphical user interface to EMBOSS.

PMID- 18628874
TI  - SNP and mutation data on the web - hidden treasures for uncovering.
AB  - SNP data has grown exponentially over the last two years, SNP database evolution
      has matched this growth, as initial development of several independent SNP
      databases has given way to one central SNP database, dbSNP. Other SNP databases
      have instead evolved to complement this central database by providing gene
      specific focus and an increased level of curation and analysis on subsets of
      data, derived from the central data set. By contrast, human mutation data, which
      has been collected over many years, is still stored in disparate sources,
      although moves are afoot to move to a similar central database. These
      developments are timely, human mutation and polymorphism data both hold
      complementary keys to a better understanding of how genes function and
      malfunction in disease. The impending availability of a complete human genome
      presents us with an ideal framework to integrate both these forms of data, as our
      understanding of the mechanisms of disease increase, the full genomic context of
      variation may become increasingly significant.

PMID- 18628875
TI  - Integrating genotypic data with transcriptomic and proteomic data.
AB  - Historically genotypic variation has been detected at the phenotypic level, at
      the metabolic level, and at the protein chemistry level. Advances in technology
      have allowed its direct visualisation at the level of DNA variation.
      Nevertheless, there is still an enormous interest in phenotypic, metabolic and
      protein property variability, since such variation gives insights into potential
      functionally important differences conferred by genetic variation. High
      throughput transcriptomics and proteomics applied to different individuals drawn
      from a population has the potential to identify the functional consequences of
      genetic variability, in terms of either differences in expression of mRNA or in
      terms of differences in the quantities, pI(s) or molecular weight(s) of an
      expressed protein. Family studies can define the genetic component of such
      variation (segregation analysis) and with the genotyping of well-spaced markers
      can map the causative factors to broad chromosomal regions (linkage analysis).
      Association studies in the variant proteins have the greatest power to confirm
      the presence of cis-acting genetic variants. The most powerful study designs may
      combine elements of both family and association studies applied to proteomic and
      transcriptomic analyses. Such studies may provide appreciable advances in our
      understanding of the genetic aetiology of complex disorders.

PMID- 18628876
TI  - Ontology based document enrichment in bioinformatics.
AB  - Controlled vocabularies are common within bioinformatics resources. They can be
      used to give a summary of the knowledge held about a particular entity. They are
      also used to constrain values given for particular attributes of an entity. This
      helps create a shared understanding of a domain and aids increased precision and
      recall during querying of resources. Ontologies can also provide such facilities,
      but can also enhance their utility. Controlled vocabularies are often simply
      lists of words, but may be viewed as a kind of ontology. Ideally ontologies are
      structurally enriched with relationships between terms within the vocabulary. Use
      of such rich forms of vocabularies in database annotation could enhance those
      resources usability by both humans and computers. The representation of the
      knowledge content of biological resources in a computationally accessible form
      opens the prospect of greater support for a biologist investigating new data.

PMID- 18628877
TI  - expression profiling of all protein-coding genes in wild-type and three DNA
      repair-deficient substrains of Escherichia coli K-12.
AB  - Gene chips or cDNA arrays of the entire set of Escherichia coli (E. coli) K12
      genes were used to measure the expression, at the mRNA level, of all 4290 protein
      coding genes in wild-type (WT) and three DNA repair-deficient derivative strains:
      (i) AB1157 (WT), (ii) LR39 (ada, ogt), (iii) MV1932 (alkA1, tag-1) and (iv)
      GM5555 (mutS). The aim was to investigate whether disruption of a single gene
      would result in significant deviation in the expression of other genes in these
      organisms. We describe here a simple approach for a stringent statistical
      evaluation of cDNA array data. This includes: (i) determination of intra- and
      interassay variation coefficients for different expression levels, (ii) rejection
      of biased duplicates, (iii) mathematical background determination, and (iv)
      comparison of expression levels of identical copies of a gene. The results
      demonstrated a highly significant correlation of gene expression when the mutants
      were individually compared with the wildtype. Altogether, 81 deviations of the
      expression of 59 genes were noted, out of 12,870, when 3-fold or greater up- or
      down-regulation was used as a criterion of differential expression. In the light
      of current knowledge of E. coli biology, the differential expression did not
      follow any logical pattern. In fact, the deviations may simply represent inter
      assay variation. The results obtained here with a simple model organism are
      different from those obtained with most mammalian knockouts: disruption of the
      function of a single gene does not, under good growth conditions, necessarily
      result in great changes in the expression of other genes.

PMID- 18628878
TI  - RIBDB: an SRS based infrastructure for REALIS.
AB  - The REALIS project is an EU-funded consortium for the post genomic analysis of
      the food pathogen Listeria monocytogenes. The data generated by the consortium
      members is stored under the RIBDB database, a system built using SRS which
      integrates consortium data, public databases, and applications for analysis.
      RIBDB is available to all consortium members through a web server, with the
      option of installing a local mirror of the main server for local analysis.

PMID- 18628879
TI  - REALIS: postgenomic analysis of Listeria Monocytogenes.
AB  - Listeria monocytogenes is a remarkably successful food-borne pathogen. It is
      capable a) of surviving and proliferating under conditions that exist within the
      food chain, such as at low temperatures, high salt and low pH and b) of
      colonizing animal host tissues after ingestion of contaminated food, causing
      opportunistic infections mainly, but not exclusively, in immunocompromised hosts.
      The ultimate goals of REALIS are two fold: Firstly, it aims to completely
      decipher all genes required for survival in and adaptation of Listeria
      monocytogenes to two very different environments, ie., the infected host and the
      external environment. Secondly, using genomics and postgenomic tools, REALIS
      seeks to precisely address fundamental questions regarding evolutionary
      relationships between pathogenic and non-pathogenic Listeria and to define
      qualities of particularly successful clonal pathovariants in causing disease.
      This project will provide both industry and health care managers with rational
      approaches to curbing food-borne contamination, minimising risks of infection and
      providing novel pharmacological approaches for halting the fulminant course of
      infection.

PMID- 18628880
TI  - Advancing post-genome data and system integration through machine learning.
AB  - Research on biological data integration has traditionally focused on the
      development of systems for the maintenance and interconnection of databases. In
      the next few years, public and private biotechnology organisations will expand
      their actions to promote the creation of a post-genome semantic web. It has
      commonly been accepted that artificial intelligence and data mining techniques
      may support the interpretation of huge amounts of integrated data. But at the
      same time, these research disciplines are contributing to the creation of content
      markup languages and sophisticated programs able to exploit the constraints and
      preferences of user domains. This paper discusses a number of issues on
      intelligent systems for the integration of bioinformatic resources.

PMID- 18628881
TI  - Discovery of single nucleotide polymorphisms and mutations by pyrosequencing.
AB  - Comparative genomics, analyzing variation among individual genomes, is an area of
      intense investigation. DNA sequencing is usually employed to look for
      polymorphisms and mutations. Pyrosequencing, a real-time DNA sequencing method,
      is emerging as a popular platform for comparative genomics. Here we review the
      use of this technology for mutation scanning, polymorphism discovery and chemical
      haplotyping. We describe the methodology and accuracy of this technique and
      discuss how to reduce the cost for large-scale analysis.

PMID- 18628883
TI  - From gene regulation to gene function: regulatory networks in bacillus subtilis.
AB  - Bacillus subtilis is a sporulating Gram-positive bacterium that lives primarily
      in the soil and associated water sources. The publication of the B. subtilis
      genome sequence and subsequent systematic functional analysis and gene regulation
      programmes, together with an extensive understanding of its biochemistry and
      physiology, makes this micro-organism a prime candidate in which to model
      regulatory networks in silico. In this paper we discuss combined molecular
      biological and bioinformatical approaches that are being developed to model this
      organism's responses to changes in its environment.

PMID- 18628884
TI  - Conference Report: The ESF Programme on Integrated Approaches for Functional
      Genomics. Workshop on 'Data Integration in Functional Genomics and Proteomics'.

PMID- 18628885
TI  - High-throughput SNP genotyping.
AB  - Whole genome approaches using single nucleotide polymorphism (SNP) markers have
      the potential to transform complex disease genetics and expedite pharmacogenetics
      research. This has led to a requirement for high-throughput SNP genotyping
      platforms. Development of a successful high-throughput genotyping platform
      depends on coupling reliable assay chemistry with an appropriate detection system
      to maximise efficiency with respect to accuracy, speed and cost. Current
      technology platforms are able to deliver throughputs in excess of 100 000
      genotypes per day, with an accuracy of >99%, at a cost of 20-30 cents per
      genotype. In order to meet the demands of the coming years, however, genotyping
      platforms need to deliver throughputs in the order of one million genotypes per
      day at a cost of only a few cents per genotype. In addition, DNA template
      requirements must be minimised such that hundreds of thousands of SNPs can be
      interrogated using a relatively small amount of genomic DNA. As such, it is
      predicted that the next generation of high-throughput genotyping platforms will
      exploit large-scale multiplex reactions and solid phase assay detection systems.

PMID- 18628886
TI  - Gramene: development and integration of trait and gene ontologies for rice.
AB  - Gramene (http://www.gramene.org/) is a comparative genome database for cereal
      crops and a community resource for rice. We are populating and curating Gramene
      with annotated rice (Oryza sativa) genomic sequence data and associated
      biological information including molecular markers, mutants, phenotypes,
      polymorphisms and Quantitative Trait Loci (QTL). In order to support queries
      across various data sets as well as across external databases, Gramene will
      employ three related controlled vocabularies. The specific goal of Gramene is,
      first to provide a Trait Ontology (TO) that can be used across the cereal crops
      to facilitate phenotypic comparisons both within and between the genera. Second,
      a vocabulary for plant anatomy terms, the Plant Ontology (PO) will facilitate the
      curation of morphological and anatomical feature information with respect to
      expression, localization of genes and gene products and the affected plant parts
      in a phenotype. The TO and PO are both in the early stages of development in
      collaboration with the International Rice Research Institute, TAIR and MaizeDB as
      part of the Plant Ontology Consortium. Finally, as part of another consortium
      comprising macromolecular databases from other model organisms, the Gene Ontology
      Consortium, we are annotating the confirmed and predicted protein entries from
      rice using both electronic and manual curation.

PMID- 18628887
TI  - A European pathogenic microorganism proteome database: construction and
      maintenance.
AB  - A relational database structure based on MS-Access and MySQL to store and manage
      proteomics data was established. This system may be used to publish two
      dimensional electrophoretic proteomics data, and also may be accessed by external
      users who want to compare their own data with those in the databases. The
      maintenance of the database is managed centrally. The producers of proteomics
      data do not need to construct a database themselves. Users can introduce mass
      spectra into the database, which allows the searching of peptide mass
      fingerprints against their own protein sequence databases. The first release
      published in January 2002 contains data from Mycobacterium tuberculosis,
      Helicobacter pylori, Borrelia garinii, Francisella tularensis, Chlamydia
      pneumoniae, Mycoplasma pneumoniae, Jurkat T-cells and mouse mammary gland
      projects (http://www.mpiib-berlin. mpg.de/2D-PAGE/).

PMID- 18628888
TI  - Deleteagene: a fast neutron deletion mutagenesis-based gene knockout system for
      plants.
AB  - Deleteagene (Delete-a-gene) is a deletion-based gene knockout system for plants.
      To obtain deletion mutants for a specific gene, random deletion libraries created
      by fast neutron mutagenesis are screened by polymerase chain reaction (PCR) using
      primers flanking the target gene. By adjusting the PCR extension time to
      preferentially amplify the deletion alleles, deletion mutants can be identified
      in pools of DNA samples with each sample representing more than a thousand mutant
      lines. In Arabidopsis, knockout plants for greater than 80% of targeted genes
      have been obtained from a population of 51,840 lines. A large number of deletion
      mutants have been identified and multiple deletion alleles are often recovered
      for targeted loci. In Arabidopsis, the method is very useful for targeting small
      genes and can be used to find deletion mutants mutating two or three tandem
      homologous genes. In addition, the method is demonstrated to be effective in rice
      as a deletion mutant for a rice gene was obtained with a similar approach.
      Because fast neutron mutagenesis is applicable to all plant genetic systems,
      Deleteagene has the potential to enable reverse genetics for a wide range of
      plant species.

PMID- 18628889
TI  - The informatics for making sense of the genome: a progress report from the
      BioPathways Consortium.

PMID- 18628890
TI  - Frequent genic rearrangements in two regions of grass genomes identified by
      comparative sequence analysis.

PMID- 18628891
TI  - An introduction to the China Rice Functional Genomics Program.
AB  - The China Rice Functional Genomics Program (CRFGP) was initiated in 1999 by the
      Ministry of Science and Technology of China under the National Basic Sciences
      Initiative and was expected to last for an initial period of five years. The
      CRFGP involves 20 research groups from the Chinese Academy of Sciences and some
      major universities and focuses on the identification of genes controlling
      flowering, plant architecture, fertility, reproduction, metabolic controls and
      stress responses in rice through a combinatorial approach based on genetics,
      molecular biology and functional genomics as well as the generation of
      intellectual properties related to crop breeding and improvements. We will
      briefly describe the mission of the CRFGP as well as its recent progress.

PMID- 18628892
TI  - MaizeDB - a functional genomics perspective.
AB  - MaizeDB (http://www.agron.missouri.edu/) has existed since the early 90's as a
      genomespecific database that is grounded in genetic maps, their documentation and
      annotation. The database management system is robust and has continuously been
      Sybase. In this brief review we provide an introduction to the database as a
      functional genomics tool and new accesses to the data: 1) probe tables by bin
      location 2) BLAST access to map data 3) cMap, a comparative map graphical tool.

PMID- 18628893
TI  - Cryptosporidium parvum genome project.
AB  - A lack of basic understanding of parasite biology has been a limiting factor in
      designing effective means of treating and preventing disease caused by
      Cryptosporidium parvum. Since the genomic DNA sequence encodes all of the
      heritable information responsible for development, disease pathogenesis,
      virulence, species permissiveness and immune resistance, a comprehensive
      knowledge of the C. parvum genome will provide the necessary information required
      for cost-effective and targeted research into disease prevention and treatment.
      With the recent advances in high-throughput automated DNA sequencing
      capabilities, large-scale genomic sequencing has become a cost-effective and time
      efficient approach to understanding the biology of an organism. In addition, the
      continued development and implementation of new software tools that can scan raw
      sequences for signs of genes and then identify clues as to potential functions,
      has provided the final realization of the potential rewards of genome sequencing.
      To further our understanding of C. parvum biology, we have initiated a random
      shotgun sequencing approach to obtain the complete sequence of the IOWA isolate
      of C. parvum. Our progress to date has demonstrated that sequencing of the C.
      parvum genome will be an efficient and costeffective method for gene discovery of
      this important eukaryotic pathogen. This will allow for the identification of key
      metabolic and immunological features of the organism that will provide the basis
      for future development of safe and effective strategies for prevention and
      treatment of disease in AIDS patients, as well as immunocompetent hosts.
      Moreover, by obtaining the complete sequence of the C. parvum genome, effective
      methods for subspecific differentiation (strain typing) and epidemiologic
      surveillance (strain tracking) of this pathogen can be developed.

PMID- 18628894
TI  - Agricultural microbes genome 2.

PMID- 18628895
TI  - Sequence search algorithms for single pass sequence identification: does one size
      fit all?
AB  - Bioinformatic tools have become essential to biologists in their quest to
      understand the vast quantities of sequence data, and now whole genomes, which are
      being produced at an ever increasing rate. Much of these sequence data are single
      pass sequences, such as sample sequences from organisms closely related to other
      organisms of interest which have already been sequenced, or cDNAs or expressed
      sequence tags (ESTs). These single-pass sequences often contain errors, including
      frameshifts, which complicate the identification of homologues, especially at the
      protein level. Therefore, sequence searches with this type of data are often
      performed at the nucleotide level. The most commonly used sequence search
      algorithms for the identification of homologues are Washington University's and
      the National Center for Biotechnology Information's (NCBI) versions of the BLAST
      suites of tools, which are to be found on websites all over the world. The work
      reported here examines the use of these tools for comparing sample sequence
      datasets to a known genome. It shows that care must be taken when choosing the
      parameters to use with the BLAST algorithms. NCBI's version of gapped BLASTn
      gives much shorter, and sometimes different, top alignments to those found using
      Washington University's version of BLASTn (which also allows for gaps), when both
      are used with their default parameters. Most of the differences in performance
      were found to be due to the choices of default parameters rather than underlying
      differences between the two algorithms. Washington University's version, used
      with defaults, compares very favourably with the results obtained using the
      accurate but computationally intensive Smith-Waterman algorithm.

PMID- 18628896
TI  - Small sample issues for microarray-based classification.
AB  - In order to study the molecular biological differences between normal and
      diseased tissues, it is desirable to perform classification among diseases and
      stages of disease using microarray-based gene-expression values. Owing to the
      limited number of microarrays typically used in these studies, serious issues
      arise with respect to the design, performance and analysis of classifiers based
      on microarray data. This paper reviews some fundamental issues facing small
      sample classification: classification rules, constrained classifiers, error
      estimation and feature selection. It discusses both unconstrained and constrained
      classifier design from sample data, and the contributions to classifier error
      from constrained optimization and lack of optimality owing to design from sample
      data. The difficulty with estimating classifier error when confined to small
      samples is addressed, particularly estimating the error from training data. The
      impact of small samples on the ability to include more than a few variables as
      classifier features is explained.

PMID- 18628898
TI  - Cancer and the web.
AB  - The applications of functional genomics, proteomics and informatics to cancer
      research have yielded a tremendous amount of information, which is growing all
      the time. Much of this information is available publicly on the Internet and
      ranges from general information about different cancers from a patient or
      clinical viewpoint, through to databases suitable for cancer researchers of all
      backgrounds, to very specific sites dedicated to individual genes or molecules. A
      simple search for 'cancer' from a typical Web browser search engine yields more
      than half a million hits; an even more specific search for 'leukaemia' (>40 000
      hits) or 'p53' (>5700 hits) yields far too many hits to allow one to identify
      particular sites of interest. This review aims to provide a brief guide to some
      of the resources and databases that can be used as springboards to home in
      rapidly on information relevant to many fields of cancer research. As such, this
      article will not focus on a single website but hopes to illustrate some of the
      ways that postgenomic biology is revolutionizing cancer research. It will cover
      genomics and proteomics approaches that have been applied to studying global
      expression patterns in cancers, in addition to providing links ranging from
      general information about cancer to specific cancer gene mutation databases.

PMID- 18628897
TI  - Conserved 'hypothetical' proteins: new hints and new puzzles.
AB  - Conserved hypothetical proteins, i.e. conserved proteins whose functions are
      still unknown, pose a challenge not just to functional genomics but also to
      general biology. For many conserved proteins, computational analysis provides
      only a general prediction of biochemical function; their exact biological
      functions have to be established through direct experimentation. In the few cases
      when this has been accomplished, the results were remarkable, revealing the
      deoxyxylulose pathway and a new essential enzyme, the ITP pyrophosphatase.
      Comparative genome analysis is also instrumental in illuminating unsolved
      problems in biology, e.g. the mechanism of FtsZ-independent cell division in
      Chlamydia, Ureaplasma and Aeropyrum or the role of uncharacterized conserved
      domains in signal transduction.

PMID- 18628900
TI  - Structural genomics on the web.
AB  - In this review we provide a brief guide to some of the resources and databases
      that can be used to locate information and aid research in the growing field of
      structural genomics. The review will provide examples, for less experienced
      users, of what can be achieved using a selection of the available sites. We hope
      that this will encourage you to use these sites to their full potential and whet
      your appetite to search for other related sites.

PMID- 18628901
TI  - Featured organism: Arabidopsis thaliana.
AB  - Arabidopsis is universally acknowledged as the model for dicotyledonous crop
      plants. Furthermore, some of the information gleaned from this small plant can be
      used to aid work on monocotyledonous crops. Here we provide an overview of the
      current state of knowledge and resources for the study of this important model
      plant, with comments on future prospects in the field from Professor Pamela Green
      and Dr Sean May.

PMID- 18628902
TI  - Whole genome analysis of a wine yeast strain.
AB  - Saccharomyces cerevisiae strains frequently exhibit rather specific phenotypic
      features needed for adaptation to a special environment. Wine yeast strains are
      able to ferment musts, for example, while other industrial or laboratory strains
      fail to do so. The genetic differences that characterize wine yeast strains are
      poorly understood, however. As a first search of genetic differences between wine
      and laboratory strains, we performed DNA-array analyses on the typical wine yeast
      strain T73 and the standard laboratory background in S288c. Our analysis shows
      that even under normal conditions, logarithmic growth in YPD medium, the two
      strains have expression patterns that differ significantly in more than 40 genes.
      Subsequent studies indicated that these differences correlate with small changes
      in promoter regions or variations in gene copy number. Blotting copy numbers vs.
      transcript levels produced patterns, which were specific for the individual
      strains and could be used for a characterization of unknown samples.

PMID- 18628903
TI  - Genetic steps to organ laterality in zebrafish.
AB  - All internal organs are asymmetric along the left-right axis. Here we report a
      genetic screen to discover mutations which perturb organ laterality. Our
      particular focus is upon whether, and how, organs are linked to each other as
      they achieve their laterally asymmetric positions. We generated mutations by ENU
      mutagenesis and examined F3 progeny using a cocktail of probes that reveal early
      primordia of heart, gut, liver and pancreas. From the 750 genomes examined, we
      isolated seven recessive mutations which affect the earliest left-right
      positioning of one or all of the organs. None of these mutations caused
      discernable defects elsewhere in the embryo at the stages examined. This is in
      contrast to those mutations we reported previously (Chen et al., 1997) which,
      along with left-right abnormalities, cause marked perturbation in gastrulation,
      body form or midline structures. We find that the mutations can be classified on
      the basis of whether they perturb relationships among organ laterality. In Class
      1 mutations, none of the organs manifest any left-right asymmetry. The heart does
      not jog to the left and normally leftpredominant BMP4 in the early heart tube
      remains symmetric. The gut tends to remain midline. There frequently is a
      remarkable bilateral duplication of liver and pancreas. Embryos with Class 2
      mutations have organotypic asymmetry but, in any given embryo, organ positions
      can be normal, reversed or randomized. Class 3 reveals a hitherto unsuspected
      gene that selectively affects laterality of heart. We find that visceral organ
      positions are predicted by the direction of the preceding cardiac jog. We
      interpret this as suggesting that normally there is linkage between cardiac and
      visceral organ laterality. Class 1 mutations, we suggest, effectively remove the
      global laterality signals, with the consequence that organ positions are
      effectively symmetrical. Embryos with Class 2 mutations do manifest linkage among
      organs, but it may be reversed, suggesting that the global signals may be present
      but incorrectly orientated in some of the embryos. That laterality decisions of
      organs may be independently perturbed, as in the Class 3 mutation, indicates that
      there are distinctive pathways for reception and organotypic interpretation of
      the global signals.

PMID- 18628904
TI  - Of plants and men.

PMID- 18628905
TI  - Interview with Michael Bevan: the Arabidopsis genome is sequenced, what next?
AB  - Professor Michael Bevan is at the John Innes Centre, Norwich, UK, where he is
      Head of the Cell and Developmental Biology Department. He was the co-ordinator of
      the European Union Arabidopsis Genome Sequencing Consortium, which contributed to
      the sequence and analysis of the complete Arabidopsis genome that was published
      late last year. He is the co-ordinator of the EC funded EXOTIC program and is
      also a member of GARNet and UK CropNet. (For more background detail on these
      projects, please see our Featured Organism: Arabidopsis thaliana piece, also in
      this issue of CFG, or visit the websites listed below).

PMID- 18628906
TI  - The complete mitochondrial genome of yarrowia lipolytica.
AB  - We here report the complete nucleotide sequence of the 47.9 kb mitochondrial (mt)
      genome from the obligate aerobic yeast Yarrowia lipolytica. It encodes, all on
      the same strand, seven subunits of NADH: ubiquinone oxidoreductase (ND1-6, ND4L),
      apocytochrome b (COB), three subunits of cytochrome oxidase (COX1, 2, 3), three
      subunits of ATP synthetase (ATP6, 8 and 9), small and large ribosomal RNAs and an
      incomplete set of tRNAs. The Y. lipolytica mt genome is very similar to the
      Hansenula wingei mt genome, as judged from blocks of conserved gene order and
      from sequence homology. The extra DNA in the Y. lipolytica mt genome consists of
      17 group 1 introns and stretches of A+Trich sequence, interspersed with
      potentially transposable GC clusters. The usual mould mt genetic code is used.
      Interestingly, there is no tRNA able to read CGN (arginine) codons. CGN codons
      could not be found in exonic open reading frames, whereas they do occur in
      intronic open reading frames. However, several of the intronic open reading
      frames have accumulated mutations and must be regarded as pseudogenes. We propose
      that this may have been triggered by the presence of untranslatable CGN codons.
      This sequence is available under EMBL Accession No. AJ307410.

PMID- 18628907
TI  - A genomic approach for the identification and classification of genes involved in
      cell wall formation and its regulation in Saccharomyces cerevisiae.
AB  - Using a hierarchical approach, 620 non-essential single-gene yeast deletants
      generated by EUROFAN I were systematically screened for cell-wall-related
      phenotypes. By analyzing for altered sensitivity to the presence of Calcofluor
      white or SDS in the growth medium, altered sensitivity to sonication, or abnormal
      morphology, 145 (23%) mutants showing at least one cell wall-related phenotype
      were selected. These were screened further to identify genes potentially involved
      in either the biosynthesis, remodeling or coupling of cell wall macromolecules or
      genes involved in the overall regulation of cell wall construction and to
      eliminate those genes with a more general, pleiotropic effect. Ninety percent of
      the mutants selected from the primary tests showed additional cell wall-related
      phenotypes. When extrapolated to the entire yeast genome, these data indicate
      that over 1200 genes may directly or indirectly affect cell wall formation and
      its regulation. Twenty-one mutants with altered levels of beta1,3-glucan synthase
      activity and five Calcofluor white-resistant mutants with altered levels of
      chitin synthase activities were found, indicating that the corresponding genes
      affect beta1,3-glucan or chitin synthesis. By selecting for increased levels of
      specific cell wall components in the growth medium, we identified 13 genes that
      are possibly implicated in different steps of cell wall assembly. Furthermore, 14
      mutants showed a constitutive activation of the cell wall integrity pathway,
      suggesting that they participate in the modulation of the pathway either directly
      acting as signaling components or by triggering the Slt2-dependent compensatory
      mechanism. In conclusion, our screening approach represents a comprehensive
      functional analysis on a genomic scale of gene products involved in various
      aspects of fungal cell wall formation.

PMID- 18628908
TI  - A re-annotation of the Saccharomyces cerevisiae genome.
AB  - Discrepancies in gene and orphan number indicated by previous analyses suggest
      that S. cerevisiae would benefit from a consistent re-annotation. In this
      analysis three new genes are identified and 46 alterations to gene coordinates
      are described. 370 ORFs are defined as totally spurious ORFs which should be
      disregarded. At least a further 193 genes could be described as very
      hypothetical, based on a number of criteria. It was found that disparate genes
      with sequence overlaps over ten amino acids (especially at the N-terminus) are
      rare in both S. cerevisiae and Sz. pombe. A new S. cerevisiae gene number
      estimate with an upper limit of 5804 is proposed, but after the removal of very
      hypothetical genes and pseudogenes this is reduced to 5570. Although this is
      likely to be closer to the true upper limit, it is still predicted to be an
      overestimate of gene number. A complete list of revised gene coordinates is
      available from the Sanger Centre (S. cerevisiae reannotation:
      ftp://ftp/pub/yeast/SCreannotation).

PMID- 18628909
TI  - Definition of the gene content of the human genome: the need for deep
      experimental verification.
AB  - Based on the analysis of the drafts of the human genome sequence, it is being
      speculated that our species may possess an unexpectedly low number of genes. The
      quality of the drafts, the impossibility of accurate gene prediction and the lack
      of sufficient transcript sequence data, however, render such speculations very
      premature. The complexity of human gene structure requires additional and
      extensive experimental verification of transcripts that may result in major
      revisions of these early estimates of the number of human genes.

PMID- 18628910
TI  - IBC - Proteomics, 1-2 March 2000, Basel Hilton, Switzerland.

PMID- 18628912
TI  - Interview with Duncan Campbell: after the draft sequence, what next for the human
      genome mapping project resource centre?

PMID- 18628911
TI  - Combining genomics, metabolome analysis, and biochemical modelling to understand
      metabolic networks.
AB  - Now that complete genome sequences are available for a variety of organisms, the
      elucidation of gene functions involved in metabolism necessarily includes a
      better understanding of cellular responses upon mutations on all levels of gene
      products, mRNA, proteins, and metabolites. Such progress is essential since the
      observable properties of organisms - the phenotypes - are produced by the
      genotype in juxtaposition with the environment. Whereas much has been done to
      make mRNA and protein profiling possible, considerably less effort has been put
      into profiling the end products of gene expression, metabolites. To date,
      analytical approaches have been aimed primarily at the accurate quantification of
      a number of pre-defined target metabolites, or at producing fingerprints of
      metabolic changes without individually determining metabolite identities. Neither
      of these approaches allows the formation of an in-depth understanding of the
      biochemical behaviour within metabolic networks. Yet, by carefully choosing
      protocols for sample preparation and analytical techniques, a number of
      chemically different classes of compounds can be quantified simultaneously to
      enable such understanding. In this review, the terms describing various
      metabolite-oriented approaches are given, and the differences among these
      approaches are outlined. Metabolite target analysis, metabolite profiling,
      metabolomics, and metabolic fingerprinting are considered. For each approach, a
      number of examples are given, and potential applications are discussed.

PMID- 18628914
TI  - SAND, a new protein family: from nucleic acid to protein structure and function
      prediction.
AB  - As a result of genome, EST and cDNA sequencing projects, there are huge numbers
      of predicted and/or partially characterised protein sequences compared with a
      relatively small number of proteins with experimentally determined function and
      structure. Thus, there is a considerable attention focused on the accurate
      prediction of gene function and structure from sequence by using bioinformatics.
      In the course of our analysis of genomic sequence from Fugu rubripes, we
      identified a novel gene, SAND, with significant sequence identity to hypothetical
      proteins predicted in Saccharomyces cerevisiae, Schizosaccharomyces pombe,
      Caenorhabditis elegans, a Drosophila melanogaster gene, and mouse and human
      cDNAs. Here we identify a further SAND homologue in human and Arabidopsis
      thaliana by use of standard computational tools. We describe the genomic
      organisation of SAND in these evolutionarily divergent species and identify
      sequence homologues from EST database searches confirming the expression of SAND
      in over 20 different eukaryotes. We confirm the expression of two different SAND
      paralogues in mammals and determine expression of one SAND in other vertebrates
      and eukaryotes. Furthermore, we predict structural properties of SAND, and
      characterise conserved sequence motifs in this protein family.

PMID- 18628915
TI  - Can bibliographic pointers for known biological data be found automatically?
      Protein interactions as a case study.
AB  - The Dictionary of Interacting Proteins (DIP) (Xenarios et al., 2000) is a large
      repository of protein interactions: its March 2000 release included 2379 protein
      pairs whose interactions have been detected by experimental methods. Even if many
      of these correspond to poorly characterized proteins, the result of massive yeast
      two-hybrid screenings, as many as 851 correspond to interactions detected using
      direct biochemical methods.We used information retrieval technology to search
      automatically for sentences in Medline abstracts that support these 851 DIP
      interactions. Surprisingly, we found correspondence between DIP protein pairs and
      Medline sentences describing their interactions in only 30% of the cases. This
      low coverage has interesting consequences regarding the quality of annotations
      (references) introduced in the database and the limitations of the application of
      information extraction (IE) technology to Molecular Biology. It is clear that the
      limitation of analyzing abstracts rather than full papers and the lack of
      standard protein names are difficulties of considerably more importance than the
      limitations of the IE methodology employed. A positive finding is the capacity of
      the IE system to identify new relations between proteins, even in a set of
      proteins previously characterized by human experts. These identifications are
      made with a considerable degree of precision. This is, to our knowledge, the
      first large scale assessment of IE capacity to detect previously known
      interactions: we thus propose the use of the DIP data set as a biological
      reference to benchmark IE systems.

PMID- 18628917
TI  - Genome-wide generation of yeast gene deletion strains.
AB  - In the year 2001 a collection of yeast strains will be completed that are deleted
      in the 6000 open reading frames selected as putative genes by the initial
      bioinformatic analysis of the Saccharomyces cerevisiae genome. The collection was
      produced by the transatlantic yeast gene deletion project, a collaboration
      involving researchers in the USA, Canada and Europe. The European effort was part
      of EUROFAN (European Functional Analysis Network) where some of the strains could
      feed into various functional analysis nodes dealing with specific areas of cell
      biology. With approximately 40% of human genes involved in heritable disease
      having a homologue in yeast and with the use of yeast in various drug discovery
      strategies, not least due to the dramatic increase in fungal infections, these
      strains will be valuable in trans-genomic studies and in specialised interest
      studies in individual laboratories. A detailed analysis of the project by the
      consortium is in preparation, here we discuss the yeast strains, reported
      findings and approaches to using this resource.

PMID- 18628918
TI  - Royal Society discussion meeting: utilising the genome sequence of parasitic
      protozoa.
AB  - Protozoan parasites cause some of the world's most important diseases. Genome
      sequencing information is rapidly being acquired and combined with new
      developments in functional genome analysis to transform our understanding of
      parasites, and to enable new approaches to combating the diseases they cause.

PMID- 18628919
TI  - Comparison of the proteomes of three yeast wild type strains: CEN.PK2, FY1679 and
      W303.
AB  - Yeast deletion strains created during gene function analysis projects very often
      show drastic phenotypic differences depending on the genetic background used.
      These results indicate the existence of important molecular differences between
      the CEN.PK2, FY1679 and W303 wild type strains. To characterise these differences
      we have compared the protein expression levels between CEN.PK2, FY1679 and W303
      strains using twodimensional gel electrophoresis and identified selected proteins
      by mass spectrometric analysis. We have found that FY1679 and W303 strains are
      more similar to each other than to the CEN.PK2 strain. This study identifies 62
      proteins that are differentially expressed between the strains and provides a
      valuable source of data for the interpretation of yeast mutant phenotypes
      observed in CEN.PK2, FY1679 and W303 strains.

PMID- 18628920
TI  - Meeting highlights: genome sequencing and biology 2001.
AB  - We bring you a report from the CSHL Genome Sequencing and Biology Meeting, which
      has a long and prestigious history. This year there were sessions on large-scale
      sequencing and analysis, polymorphisms (covering discovery and technologies and
      mapping and analysis), comparative genomics of mammalian and model organism
      genomes, functional genomics and bioinformatics.

PMID- 18628921
TI  - The second European conference on zebrafish genetics and development.

PMID- 18628922
TI  - Meeting highlights: 15 International Mouse Genome Conference.

PMID- 18628924
TI  - Effectiveness of normal saline diuresis in treating lithium overdose.
AB  - Lithium carbonate is a common treatment for mood disorders, but it has a very
      narrow therapeutic index and can be toxic to multiple organ systems.
      Unfortunately, many patients suffer toxic effects through the course of their
      therapy. We describe a patient with toxic effects from a high dose of lithium who
      was successfully treated with normal saline diuresis. We discuss the properties
      that make lithium susceptible to normal saline diuresis and explore alternative
      options for treatment of lithium toxicity.

PMID- 18628923
TI  - Intraoperative imaging of pancreas transplant allografts using indocyanine green
      with laser fluorescence.
AB  - Vascular thrombosis is a cause of allograft loss after pancreas transplantation.
      We present the use of intraoperative fluorescence imaging with the SPY imaging
      device (Novadaq Technologies Inc, Toronto, Canada) in two pancreas transplants as
      a means to assess potency of the vascular anastomoses. Intravenous indocyanine
      green 2.5 mg/mL was fluoresced with the device to create the intraoperative video
      sequences, which were recorded. After 60-day follow-up, real-time SPY imaging on
      these two pancreas transplants did not demonstrate adverse effects on patients or
      the transplanted allografts. This method of vascular imaging could prove useful
      in improving short-term graft survival and possibly lowering the thrombosis rates
      seen with pancreas transplantation. Long-term correlation studies between
      intraoperative findings and graft survival must be performed to confirm the
      utility of this imaging method.

PMID- 18628925
TI  - Long-term follow-up of patients with insomnia.
AB  - It has been suggested that patients with insomnia who are lost to follow-up
      continue to experience symptoms. From winter 2006 to spring 2007, we contacted
      consecutive patients initially seen at a multidisciplinary sleep medicine clinic
      3 to 5 years earlier and asked them about continuing symptoms. Among the 58
      patients who agreed to participate, 43 (74%) reported that they still experienced
      difficulty initiating and/or maintaining sleep. Thirty-one of those patients had
      continued to receive treatment, 11 from a sleep medicine specialist and the
      remainder from other physicians. The majority listed zolpidem or eszopiclone as
      their primary medication, and many took multiple medications, including over-the
      counter drugs and alternative medications. Most patients with insomnia were
      unaware of cognitive-behavioral therapy. These findings emphasize the need for
      primary care physicians to monitor symptoms of insomnia and to remain vigilant
      about potential treatment complications.

PMID- 18628927
TI  - Preoperative visualization of a muscular ventricular septal defect by 64-slice
      cardiac computed tomography.

PMID- 18628926
TI  - Hepatocellular carcinoma: management of an increasingly common problem.
AB  - Hepatocellular carcinoma (HCC) is a common cancer that typically occurs in the
      setting of cirrhosis and chronic hepatitis virus infections. Hepatitis B and C
      account for approximately 80% of cases worldwide. HCC is currently the fifth most
      common malignancy in men and the eighth in women worldwide; its incidence is
      increasing dramatically in many parts of the world. Recognition of those at risk
      and early diagnosis by surveillance with imaging, with or without serologic
      testing, are extremely important. Many highly effective and even curative
      therapies are now available and include resection, liver transplantation, and
      local ablation. Appropriate application of these interventions offers hope of
      prolonged survival to many patients with this otherwise lethal complication of
      liver disease.

PMID- 18628929
TI  - Conflict resolution in a different culture.

PMID- 18628928
TI  - Some observations on mitral and aortic valve disease.

PMID- 18628930
TI  - Is being left-handed a handicap? The short and useless answer is "yes and no.".

PMID- 18628931
TI  - Perry edward Gross, MD: a conversation with the editor.

PMID- 18628932
TI  - Brown adipose tissue in a newborn.

PMID- 18628933
TI  - Gastrointestinal bleeding and cutaneous nodules.

PMID- 18628934
TI  - Wolff-Parkinson-White-type ventricular preexcitation mimicking left ventricular
      hypertrophy and an inferoposterior myocardial infarct.

PMID- 18628936
TI  - What is a health care liability claim under Texas law?

PMID- 18628935
TI  - Doripenem (Doribax): the newest addition to the carbapenems.
AB  - Carbapenems are a class of antimicrobials structurally related to penicillin.
      Doripenem, the newest agent in this class, was recently approved by the Food and
      Drug Administration for the treatment of complicated intra-abdominal infections
      and complicated urinary tract infections. Its spectrum of activity is similar to
      that of meropenem and imipenem/cilastatin. Some studies indicate that
      approximately 29% of carbapenem-resistant Pseudomonas aeruginosa isolates may
      remain sensitive to doripenem, although the clinical relevance of that finding
      has not been determined. Clinical studies, which have been published only in
      abstract form to date, have found doripenem to be similar to comparator agents.
      The most common adverse effects related to doripenem therapy were headache,
      nausea, diarrhea, rash, and phlebitis. Doripenem, like the other carbapenems, may
      also cause seizures. Because of the lack of published data, the lack of clear
      advantages over meropenem, and the increased cost compared with meropenem,
      doripenem will not be available for use at Baylor University Medical Center
      except by infectious diseases specialists.

PMID- 18628937
TI  - Facts and ideas from anywhere.

PMID- 18628939
TI  - CFG and the New Year.

PMID- 18628940
TI  - Many Genbank entries for complete microbial genomes violate the Genbank standard.
AB  - A survey of Genbank entries for complete microbial genomes reveals that the
      majority do not conform to the Genbank standard. Typical deviations from the
      Genbank standard include records with information in incorrect fields, addition
      of extraneous and confusing information within a field, and omission of useful
      fields. This situation results from two principal causes: genome centres do not
      submit Genbank records in the proper form and the Genbank, EMBL and DDBJ staffs
      do not enforce the database standards that they have defined.

PMID- 18628938
TI  - Analysis of Venezuelan equine encephalitis replicon particles packaged in
      different coats.
AB  - BACKGROUND: The Venezuelan equine encephalitis (VEE) virus replicon system was
      used to produce virus-like replicon particles (VRP) packaged with a number of
      different VEE-derived glycoprotein (GP) coats. The GP coat is believed to be
      responsible for the cellular tropism noted for VRP and it is possible that
      different VEE GP coats may have different affinities for cells. We examined VRP
      packaged in four different VEE GP coats for their ability to infect cells in
      vitro and to induce both humoral and cellular immune responses in vivo.
      METHODOLOGY/PRINCIPAL FINDINGS: The VRP preparations were characterized to
      determine both infectious units (IU) and genome equivalents (GE) prior to in vivo
      analysis. VRP packaged with different VEE GP coats demonstrated widely varying
      GE/IU ratios based on Vero cell infectivity. BALB/c mice were immunized with the
      different VRP based on equal GE titers and the humoral and cellular responses to
      the expressed HIV gag gene measured. The magnitude of the immune responses
      measured in mice revealed small but significant differences between different GP
      coats when immunization was based on GE titers. CONCLUSIONS/SIGNIFICANCE: We
      suggest that care should be taken when alternative coat proteins are used to
      package vector-based systems as the titers determined by cell culture infection
      may not represent accurate particle numbers and in turn may not accurately
      represent actual in vivo dose.

PMID- 18628941
TI  - Featured organism: reductive evolution in bacteria: Buchnera sp., Rickettsia
      prowazekii and Mycobacterium leprae.
AB  - Obligate intracellular bacteria commonly have much reduced genome sizes compared
      to their nearest free-living relatives. One reason for this is reductive
      evolution: the loss of genes rendered non-essential due to the intracellular
      habitat. This can occur because of the presence of orthologous genes in the host,
      combined with the ability of the bacteria to import the protein or metabolite
      products of the host genes. In this article we take a look at three such bacteria
      whose genomes have been fully sequenced. Buchnera is an endosymbiont of the pea
      aphid, Acyrthosiphon pisum, the relationship between these two organisms being so
      essential that neither can reproduce in the absence of the other. Rickettsia
      prowazekii is the causative agent of louse-borne typhus in humans and
      Mycobacterium leprae infection of humans leads to leprosy. Both of these human
      pathogens have fastidious growth requirements, which has made them very difficult
      to study.

PMID- 18628943
TI  - From genome to function: systematic analysis of the soil bacterium bacillus
      subtilis.
AB  - Bacillus subtilis is a sporulating Gram-positive bacterium that lives primarily
      in the soil and associated water sources. Whilst this bacterium has been studied
      extensively in the laboratory, relatively few studies have been undertaken to
      study its activity in natural environments. The publication of the B. subtilis
      genome sequence and subsequent systematic functional analysis programme have
      provided an opportunity to develop tools for analysing the role and expression of
      Bacillus genes in situ. In this paper we discuss analytical approaches that are
      being developed to relate genes to function in environments such as the
      rhizosphere.

PMID- 18628944
TI  - Transmembrane protein oxygen content and compartmentalization of cells.
AB  - Recently, there was a report that explored the oxygen content of transmembrane
      proteins over macroevolutionary time scales where the authors observed a
      correlation between the geological time of appearance of compartmentalized cells
      with atmospheric oxygen concentration. The authors predicted, characterized and
      correlated the differences in the structure and composition of transmembrane
      proteins from the three kingdoms of life with atmospheric oxygen concentrations
      in geological timescale. They hypothesized that transmembrane proteins in ancient
      taxa were selectively excluding oxygen and as this constraint relaxed over time
      with increase in the levels of atmospheric oxygen the size and number of
      communication-related transmembrane proteins increased. In summary, they
      concluded that compartmentalized and non-compartmentalized cells can be
      distinguished by how oxygen is partitioned at the proteome level. They derived
      this conclusion from an analysis of 19 taxa. We extended their analysis on a
      larger sample of taxa comprising 309 eubacterial, 34 archaeal, and 30 eukaryotic
      complete proteomes and observed that one can not absolutely separate the two
      groups of cells based on partition of oxygen in their membrane proteins. In
      addition, the origin of compartmentalized cells is likely to have been driven by
      an innovation than happened 2700 million years ago in the membrane composition of
      cells that led to the evolution of endocytosis and exocytosis rather than due to
      the rise in concentration of atmospheric oxygen.

PMID- 18628945
TI  - Forty years trends in timing of pubertal growth spurt in 157,000 Danish school
      children.
AB  - BACKGROUND: Entering puberty is an important milestone in reproductive life and
      secular changes in the timing of puberty may be an important indicator of the
      general reproductive health in a population. Too early puberty is associated with
      several psychosocial and health problems. The aim of our study was to determine
      if the age at onset of pubertal growth spurt (OGS) and at peak height velocity
      (PHV) during puberty show secular trends during four decades in a large cohort of
      school children. METHODS AND FINDINGS: Annual measurements of height were
      available in all children born from 1930 to 1969 who attended primary school in
      the Copenhagen Municipality. 135,223 girls and 21,612 boys fulfilled the criteria
      for determining age at OGS and age at PHV. These physiological events were used
      as markers of pubertal development in our computerized method in order to
      evaluate any secular trends in pubertal maturation during the study period (year
      of birth 1930 to 1969). In this period, age at OGS declined statistically
      significantly by 0.2 and 0.4 years in girls and boys, respectively, whereas age
      at PHV declined statistically significantly by 0.5 and 0.3 years in girls and
      boys, respectively. The decline was non-linear with a levelling off in the
      children born between 1940 and 1955. The duration of puberty, as defined by the
      difference between age at OGS and age at PHV, increased slightly in boys, whereas
      it decreased in girls. CONCLUSION: Our finding of declining age at OGS and at PHV
      indicates a secular trend towards earlier sexual maturation of Danish children
      born between 1930 and 1969. Only minor changes were observed in duration of
      puberty assessed by the difference in ages at OGS and PHV.

PMID- 18628946
TI  - Willingness of men who have sex with men (MSM) in the United States to be
      circumcised as adults to reduce the risk of HIV infection.
AB  - BACKGROUND: Circumcision reduces HIV acquisition among heterosexual men in
      Africa, but it is unclear if circumcision may reduce HIV acquisition among men
      who have sex with men (MSM) in the United States, or whether MSM would be willing
      to be circumcised if recommended. METHODS: We interviewed presumed-HIV negative
      MSM at gay pride events in 2006. We asked uncircumcised respondents about
      willingness to be circumcised if it were proven to reduce risk of HIV among MSM
      and perceived barriers to circumcision. Multivariate logistic regression was used
      to identify covariates associated with willingness to be circumcised. RESULTS: Of
      780 MSM, 133 (17%) were uncircumcised. Of these, 71 (53%) were willing to be
      circumcised. Willingness was associated with black race (exact odds ratio [OR]:
      3.4, 95% confidence interval [CI]: 1.3-9.8), non-injection drug use (OR: 6.1, 95%
      CI: 1.8-23.7) and perceived reduced risk of penile cancer (OR: 4.7, 95% CI: 2.0
      11.9). The most commonly endorsed concerns about circumcision were post-surgical
      pain and wound infection. CONCLUSIONS: Over half of uncircumcised MSM, especially
      black MSM, expressed willingness to be circumcised. Perceived risks and benefits
      of circumcision should be a part of educational materials if circumcision is
      recommended for MSM in the United States.

PMID- 18628948
TI  - Fast nonnegative matrix factorization algorithms using projected gradient
      approaches for large-scale problems.
AB  - Recently, a considerable growth of interest in projected gradient (PG) methods
      has been observed due to their high efficiency in solving large-scale convex
      minimization problems subject to linear constraints. Since the minimization
      problems underlying nonnegative matrix factorization (NMF) of large matrices well
      matches this class of minimization problems, we investigate and test some recent
      PG methods in the context of their applicability to NMF. In particular, the paper
      focuses on the following modified methods: projected Landweber, Barzilai-Borwein
      gradient projection, projected sequential subspace optimization (PSESOP),
      interior-point Newton (IPN), and sequential coordinate-wise. The proposed and
      implemented NMF PG algorithms are compared with respect to their performance in
      terms of signal-to-interference ratio (SIR) and elapsed time, using a simple
      benchmark of mixed partially dependent nonnegative signals.

PMID- 18628947
TI  - Genistein-supplemented diet decreases malaria liver infection in mice and
      constitutes a potential prophylactic strategy.
AB  - In tropical regions millions of people still live at risk of malaria infection.
      Indeed the emergence of resistance to chloroquine and other drugs in use in these
      areas reinforces the need to implement alternative prophylactic strategies.
      Genistein is a naturally occurring compound that is widely used as a food
      supplement and is thought to be effective in countering several pathologies.
      Results presented here show that genistein inhibits liver infection by the
      Plasmodium parasite, the causative agent of malaria. In vitro, genistein
      decreased the infection rates of both mouse and human hepatoma cells by
      inhibiting the early stages of the parasite's intracellular development. Oral or
      intraperitoneal administration of genistein decreased the liver parasite load of
      P. berghei-infected mice. Moreover, mice fed on a genistein-supplemented diet
      showed a significant reduction in Plasmodium liver infection as well as a reduced
      blood parasitemia and partial protection from severe disease. Since genistein is
      a safe, low-cost, natural compound that can be used permanently in a diet, we
      propose its use as a prophylactic agent against malaria for endemic populations
      and long-time travelers.

PMID- 18628949
TI  - Modulating vesicle priming reveals that vesicle immobilization is necessary but
      not sufficient for fusion-competence.
AB  - In neurons and neuroendocrine cells, docked vesicles need to undergo priming to
      become fusion competent. Priming is a multi-step process that was shown to be
      associated with vesicle immobilization. However, it is not known whether vesicle
      immobilization is sufficient to acquire complete fusion competence. To extend our
      understanding of the physical manifestation of vesicle priming, we took advantage
      of tomosyn, a SNARE-related protein that specifically inhibits vesicle priming,
      and measured its effect on vesicle dynamics in live chromaffin cells using total
      internal reflection fluorescence microscopy. We show here that while in control
      cells vesicles undergo immobilization before fusion, vesicle immobilization is
      attenuated in tomosyn overexpressing cells. This in turn increases the turnover
      rate of vesicles near the membrane and attenuates the fusion of newcomer
      vesicles. Moreover, the release probability of immobile vesicles in tomosyn cells
      is significantly reduced, suggesting that immobilization is an early and
      necessary step in priming but is insufficient, as further molecular processes are
      needed to acquire complete fusion competence. Using tomosyn as a molecular tool
      we provide a mechanistic link between functional docking and priming and suggest
      that functional docking is the first step in vesicle priming, followed by
      molecular modifications that do not translate into changes in vesicle mobility.

PMID- 18628951
TI  - Does sex-selective predation stabilize or destabilize predator-prey dynamics?
AB  - BACKGROUND: Little is known about the impact of prey sexual dimorphism on
      predator-prey dynamics and the impact of sex-selective harvesting and trophy
      hunting on long-term stability of exploited populations. METHODOLOGY AND
      PRINCIPAL FINDINGS: We review the quantitative evidence for sex-selective
      predation and study its long-term consequences using several simple predator-prey
      models. These models can be also interpreted in terms of feedback between
      harvesting effort and population size of the harvested species under open-access
      exploitation. Among the 81 predator-prey pairs found in the literature, male bias
      in predation is 2.3 times as common as female bias. We show that long-term
      effects of sex-selective predation depend on the interplay of predation bias and
      prey mating system. Predation on the 'less limiting' prey sex can yield a stable
      predator-prey equilibrium, while predation on the other sex usually destabilizes
      the dynamics and promotes population collapses. For prey mating systems that we
      consider, males are less limiting except for polyandry and polyandrogyny, and
      male-biased predation alone on such prey can stabilize otherwise unstable
      dynamics. On the contrary, our results suggest that female-biased predation on
      polygynous, polygynandrous or monogamous prey requires other stabilizing
      mechanisms to persist. CONCLUSIONS AND SIGNIFICANCE: Our modelling results
      suggest that the observed skew towards male-biased predation might reflect, in
      addition to sexual selection, the evolutionary history of predator-prey
      interactions. More focus on these phenomena can yield additional and interesting
      insights as to which mechanisms maintain the persistence of predator-prey pairs
      over ecological and evolutionary timescales. Our results can also have
      implications for long-term sustainability of harvesting and trophy hunting of
      sexually dimorphic species.

PMID- 18628950
TI  - Evolution of Streptococcus pneumoniae and its close commensal relatives.
AB  - Streptococcus pneumoniae is a member of the Mitis group of streptococci which,
      according to 16S rRNA-sequence based phylogenetic reconstruction, includes 12
      species. While other species of this group are considered prototypes of commensal
      bacteria, S. pneumoniae is among the most frequent microbial killers worldwide.
      Population genetic analysis of 118 strains, supported by demonstration of a
      distinct cell wall carbohydrate structure and competence pheromone sequence
      signature, shows that S. pneumoniae is one of several hundred evolutionary
      lineages forming a cluster separate from Streptococcus oralis and Streptococcus
      infantis. The remaining lineages of this distinct cluster are commensals
      previously collectively referred to as Streptococcus mitis and each represent
      separate species by traditional taxonomic standard. Virulence genes including the
      operon for capsule polysaccharide synthesis and genes encoding IgA1 protease,
      pneumolysin, and autolysin were randomly distributed among S. mitis lineages.
      Estimates of the evolutionary age of the lineages, the identical location of
      remnants of virulence genes in the genomes of commensal strains, the pattern of
      genome reductions, and the proportion of unique genes and their origin support
      the model that the entire cluster of S. pneumoniae, S. pseudopneumoniae, and S.
      mitis lineages evolved from pneumococcus-like bacteria presumably pathogenic to
      the common immediate ancestor of hominoids. During their adaptation to a
      commensal life style, most of the lineages gradually lost the majority of genes
      determining virulence and became genetically distinct due to sexual isolation in
      their respective hosts.

PMID- 18628952
TI  - Protein solubility and folding enhancement by interaction with RNA.
AB  - While basic mechanisms of several major molecular chaperones are well understood,
      this machinery has been known to be involved in folding of only limited number of
      proteins inside the cells. Here, we report a chaperone type of protein folding
      facilitated by interaction with RNA. When an RNA-binding module is placed at the
      N-terminus of aggregation-prone target proteins, this module, upon binding with
      RNA, further promotes the solubility of passenger proteins, potentially leading
      to enhancement of proper protein folding. Studies on in vitro refolding in the
      presence of RNA, coexpression of RNA molecules in vivo and the mutants with
      impaired RNA binding ability suggests that RNA can exert chaperoning effect on
      their bound proteins. The results suggest that RNA binding could affect the
      overall kinetic network of protein folding pathway in favor of productive folding
      over off-pathway aggregation. In addition, the RNA binding-mediated solubility
      enhancement is extremely robust for increasing soluble yield of passenger
      proteins and could be usefully implemented for high-throughput protein expression
      for functional and structural genomic research initiatives. The RNA-mediated
      chaperone type presented here would give new insights into de novo folding in
      vivo.

PMID- 18628953
TI  - Role of Sox-9, ER81 and VE-cadherin in retinoic acid-mediated trans
      differentiation of breast cancer cells.
AB  - Many aspects of development, tumor growth and metastasis depend upon the
      provision of an adequate vasculature. This can be a result of regulated
      angiogenesis, recruitment of circulating endothelial progenitors and/or vascular
      trans-differentiation. The present study demonstrates that treatment of SKBR-3
      breast cancer cells with retinoic acid (RA), an important regulator of
      embryogenesis, cancer and other diseases, stimulates the formation of networks in
      Matrigel. RA-treatment of SKBR-3 cells co-cultured with human umbilical vein
      endothelial cells resulted in the formation of mixed structures. RA induces
      expression of many endothelial genes including vascular endothelial (VE)
      cadherin. VE-cadherin was also induced by RA in a number of other breast cancer
      cells. We show that RA-induced VE-cadherin is responsible for the RA-induced
      morphological changes. RA rapidly induced the expression of Sox-9 and ER81, which
      in turn form a complex on the VE-cadherin promoter and are required to mediate
      the transcriptional regulation of VE-cadherin by RA. These data indicate that RA
      may promote the expression of endothelial genes resulting in endothelial-like
      differentiation, or provide a mechanism whereby circulating endothelial
      progenitor cells could be incorporated into a growing organ or tumor.

PMID- 18628954
TI  - Age-specific epigenetic drift in late-onset Alzheimer's disease.
AB  - Despite an enormous research effort, most cases of late-onset Alzheimer's disease
      (LOAD) still remain unexplained and the current biomedical science is still a
      long way from the ultimate goal of revealing clear risk factors that can help in
      the diagnosis, prevention and treatment of the disease. Current theories about
      the development of LOAD hinge on the premise that Alzheimer's arises mainly from
      heritable causes. Yet, the complex, non-Mendelian disease etiology suggests that
      an epigenetic component could be involved. Using MALDI-TOF mass spectrometry in
      post-mortem brain samples and lymphocytes, we have performed an analysis of DNA
      methylation across 12 potential Alzheimer's susceptibility loci. In the LOAD
      brain samples we identified a notably age-specific epigenetic drift, supporting a
      potential role of epigenetic effects in the development of the disease.
      Additionally, we found that some genes that participate in amyloid-beta
      processing (PSEN1, APOE) and methylation homeostasis (MTHFR, DNMT1) show a
      significant interindividual epigenetic variability, which may contribute to LOAD
      predisposition. The APOE gene was found to be of bimodal structure, with a
      hypomethylated CpG-poor promoter and a fully methylated 3'-CpG-island, that
      contains the sequences for the epsilon4-haplotype, which is the only undisputed
      genetic risk factor for LOAD. Aberrant epigenetic control in this CpG-island may
      contribute to LOAD pathology. We propose that epigenetic drift is likely to be a
      substantial mechanism predisposing individuals to LOAD and contributing to the
      course of disease.

PMID- 18628955
TI  - Massively parallel interrogation of aptamer sequence, structure and function.
AB  - BACKGROUND: Optimization of high affinity reagents is a significant bottleneck in
      medicine and the life sciences. The ability to synthetically create thousands of
      permutations of a lead high-affinity reagent and survey the properties of
      individual permutations in parallel could potentially relieve this bottleneck.
      Aptamers are single stranded oligonucleotides affinity reagents isolated by in
      vitro selection processes and as a class have been shown to bind a wide variety
      of target molecules. METHODOLOGY/PRINCIPAL FINDINGS: High density DNA microarray
      technology was used to synthesize, in situ, arrays of approximately 3,900 aptamer
      sequence permutations in triplicate. These sequences were interrogated on-chip
      for their ability to bind the fluorescently-labeled cognate target,
      immunoglobulin E, resulting in the parallel execution of thousands of
      experiments. Fluorescence intensity at each array feature was well resolved and
      shown to be a function of the sequence present. The data demonstrated high intra-
      and inter-chip correlation between the same features as well as among the
      sequence triplicates within a single array. Consistent with aptamer mediated IgE
      binding, fluorescence intensity correlated strongly with specific aptamer
      sequences and the concentration of IgE applied to the array. CONCLUSION AND
      SIGNIFICANCE: The massively parallel sequence-function analyses provided by this
      approach confirmed the importance of a consensus sequence found in all 21 of the
      original IgE aptamer sequences and support a common stem:loop structure as being
      the secondary structure underlying IgE binding. The microarray application, data
      and results presented illustrate an efficient, high information content approach
      to optimizing aptamer function. It also provides a foundation from which to
      better understand and manipulate this important class of high affinity
      biomolecules.

PMID- 18628956
TI  - TAF6delta controls apoptosis and gene expression in the absence of p53.
AB  - BACKGROUND: Life and death decisions of metazoan cells hinge on the balance
      between the expression of pro- versus anti-apoptotic gene products. The general
      RNA polymerase II transcription factor, TFIID, plays a central role in the
      regulation of gene expression through its core promoter recognition and co
      activator functions. The core TFIID subunit TAF6 acts in vitro as an essential co
      activator of transcription for the p53 tumor suppressor protein. We previously
      identified a splice variant of TAF6, termed TAF6delta that can be induced during
      apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the impact of TAF6delta
      on cell death and gene expression, we have employed modified antisense
      oligonucleotides to enforce expression of endogenous TAF6delta. The induction of
      endogenous TAF6delta triggered apoptosis in tumor cell lines, including cells
      devoid of p53. Microarray experiments revealed that TAF6delta activates gene
      expression independently of cellular p53 status. CONCLUSIONS: Our data define
      TAF6delta as a pivotal node in a signaling pathway that controls gene expression
      programs and apoptosis in the absence of p53.

PMID- 18628957
TI  - The protein phosphatase 7 regulates phytochrome signaling in Arabidopsis.
AB  - The psi2 mutant of Arabidopsis displays amplification of the responses controlled
      by the red/far red light photoreceptors phytochrome A (phyA) and phytochrome B
      (phyB) but no apparent defect in blue light perception. We found that loss-of
      function alleles of the protein phosphatase 7 (AtPP7) are responsible for the
      light hypersensitivity in psi2 demonstrating that AtPP7 controls the levels of
      phytochrome signaling. Plants expressing reduced levels of AtPP7 mRNA display
      reduced blue-light induced cryptochrome signaling but no noticeable deficiency in
      phytochrome signaling. Our genetic analysis suggests that phytochrome signaling
      is enhanced in the AtPP7 loss of function alleles, including in blue light, which
      masks the reduced cryptochrome signaling. AtPP7 has been found to interact both
      in yeast and in planta assays with nucleotide-diphosphate kinase 2 (NDPK2), a
      positive regulator of phytochrome signals. Analysis of ndpk2-psi2 double mutants
      suggests that NDPK2 plays a critical role in the AtPP7 regulation of the
      phytochrome pathway and identifies NDPK2 as an upstream element involved in the
      modulation of the salicylic acid (SA)-dependent defense pathway by light. Thus,
      cryptochrome- and phytochrome-specific light signals synchronously control their
      relative contribution to the regulation of plant development. Interestingly, PP7
      and NDPK are also components of animal light signaling systems.

PMID- 18628958
TI  - Global regulation of nucleotide biosynthetic genes by c-Myc.
AB  - BACKGROUND: The c-Myc transcription factor is a master regulator and integrates
      cell proliferation, cell growth and metabolism through activating thousands of
      target genes. Our identification of direct c-Myc target genes by chromatin
      immunoprecipitation (ChIP) coupled with pair-end ditag sequencing analysis (ChIP
      PET) revealed that nucleotide metabolic genes are enriched among c-Myc targets,
      but the role of Myc in regulating nucleotide metabolic genes has not been
      comprehensively delineated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that
      the majority of genes in human purine and pyrimidine biosynthesis pathway were
      induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model
      cell line. The majority of these genes were also responsive to the ligand
      activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat
      fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also
      responsive to Myc activation in transgenic mouse livers in vivo. To determine the
      functional significance of c-Myc regulation of nucleotide metabolism, we sought
      to determine the effect of loss of function of direct Myc targets inosine
      monophosphate dehydrogenases (IMPDH1 and IMPDH2) on c-Myc-induced cell growth and
      proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic
      acid (MPA) and found that MPA dramatically inhibits c-Myc-induced P493-6 cell
      proliferation through S-phase arrest and apoptosis. CONCLUSIONS/SIGNIFICANCE:
      Taken together, these results demonstrate the direct induction of nucleotide
      metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in
      cells with diminished IMPDH activity suggests that nucleotide pool balance is
      essential for c-Myc's orchestration of DNA replication, such that uncoupling of
      these two processes create DNA replication stress and apoptosis.

PMID- 18628959
TI  - Genome holography: deciphering function-form motifs from gene expression data.
AB  - BACKGROUND: DNA chips allow simultaneous measurements of genome-wide response of
      thousands of genes, i.e. system level monitoring of the gene-network activity.
      Advanced analysis methods have been developed to extract meaningful information
      from the vast amount of raw gene-expression data obtained from the microarray
      measurements. These methods usually aimed to distinguish between groups of
      subjects (e.g., cancer patients vs. healthy subjects) or identifying marker genes
      that help to distinguish between those groups. We assumed that motifs related to
      the internal structure of operons and gene-networks regulation are also embedded
      in microarray and can be deciphered by using proper analysis.
      METHODOLOGY/PRINCIPAL FINDINGS: The analysis presented here is based on
      investigating the gene-gene correlations. We analyze a database of gene
      expression of Bacillus subtilis exposed to sub-lethal levels of 37 different
      antibiotics. Using unsupervised analysis (dendrogram) of the matrix of normalized
      gene-gene correlations, we identified the operons as they form distinct clusters
      of genes in the sorted correlation matrix. Applying dimension-reduction algorithm
      (Principal Component Analysis, PCA) to the matrices of normalized correlations
      reveals functional motifs. The genes are placed in a reduced 3-dimensional space
      of the three leading PCA eigen-vectors according to their corresponding eigen
      values. We found that the organization of the genes in the reduced PCA space
      recovers motifs of the operon internal structure, such as the order of the genes
      along the genome, gene separation by non-coding segments, and translational start
      and end regions. In addition to the intra-operon structure, it is also possible
      to predict inter-operon relationships, operons sharing functional regulation
      factors, and more. In particular, we demonstrate the above in the context of the
      competence and sporulation pathways. CONCLUSIONS/SIGNIFICANCE: We demonstrated
      that by analyzing gene-gene correlation from gene-expression data it is possible
      to identify operons and to predict unknown internal structure of operons and gene
      networks regulation.

PMID- 18628960
TI  - A 28,000 years old Cro-Magnon mtDNA sequence differs from all potentially
      contaminating modern sequences.
AB  - BACKGROUND: DNA sequences from ancient specimens may in fact result from
      undetected contamination of the ancient specimens by modern DNA, and the problem
      is particularly challenging in studies of human fossils. Doubts on the
      authenticity of the available sequences have so far hampered genetic comparisons
      between anatomically archaic (Neandertal) and early modern (Cro-Magnoid)
      Europeans. METHODOLOGY/PRINCIPAL FINDINGS: We typed the mitochondrial DNA (mtDNA)
      hypervariable region I in a 28,000 years old Cro-Magnoid individual from the
      Paglicci cave, in Italy (Paglicci 23) and in all the people who had contact with
      the sample since its discovery in 2003. The Paglicci 23 sequence, determined
      through the analysis of 152 clones, is the Cambridge reference sequence, and
      cannot possibly reflect contamination because it differs from all potentially
      contaminating modern sequences. CONCLUSIONS/SIGNIFICANCE: The Paglicci 23
      individual carried a mtDNA sequence that is still common in Europe, and which
      radically differs from those of the almost contemporary Neandertals,
      demonstrating a genealogical continuity across 28,000 years, from Cro-Magnoid to
      modern Europeans. Because all potential sources of modern DNA contamination are
      known, the Paglicci 23 sample will offer a unique opportunity to get insight for
      the first time into the nuclear genes of early modern Europeans.

PMID- 18628961
TI  - Seventeen new complete mtDNA sequences reveal extensive mitochondrial genome
      evolution within the Demospongiae.
AB  - Two major transitions in animal evolution--the origins of multicellularity and
      bilaterality--correlate with major changes in mitochondrial DNA (mtDNA)
      organization. Demosponges, the largest class in the phylum Porifera, underwent
      only the first of these transitions and their mitochondrial genomes display a
      peculiar combination of ancestral and animal-specific features. To get an insight
      into the evolution of mitochondrial genomes within the Demospongiae, we
      determined 17 new mtDNA sequences from this group and analyzing them with five
      previously published sequences. Our analysis revealed that all demosponge mtDNAs
      are 16- to 25-kbp circular molecules, containing 13-15 protein genes, 2 rRNA
      genes, and 2-27 tRNA genes. All but four pairs of sampled genomes had unique gene
      orders, with the number of shared gene boundaries ranging from 1 to 41. Although
      most demosponge species displayed low rates of mitochondrial sequence evolution,
      a significant acceleration in evolutionary rates occurred in the G1 group (orders
      Dendroceratida, Dictyoceratida, and Verticillitida). Large variation in mtDNA
      organization was also observed within the G0 group (order Homosclerophorida)
      including gene rearrangements, loss of tRNA genes, and the presence of two
      introns in Plakortis angulospiculatus. While introns are rare in modern-day
      demosponge mtDNA, we inferred that at least one intron was present in cox1 of the
      common ancestor of all demosponges. Our study uncovered an extensive
      mitochondrial genomic diversity within the Demospongiae. Although all sampled
      mitochondrial genomes retained some ancestral features, including a minimally
      modified genetic code, conserved structures of tRNA genes, and presence of
      multiple non-coding regions, they vary considerably in their size, gene content,
      gene order, and the rates of sequence evolution. Some of the changes in
      demosponge mtDNA, such as the loss of tRNA genes and the appearance of hairpin
      containing repetitive elements, occurred in parallel in several lineages and
      suggest general trends in demosponge mtDNA evolution.

PMID- 18628962
TI  - A meta-analysis of microarray gene expression in mouse stem cells: redefining
      stemness.
AB  - BACKGROUND: While much progress has been made in understanding stem cell (SC)
      function, a complete description of the molecular mechanisms regulating SCs is
      not yet established. This lack of knowledge is a major barrier holding back the
      discovery of therapeutic uses of SCs. We investigated the value of a novel meta
      analysis of microarray gene expression in mouse SCs to aid the elucidation of
      regulatory mechanisms common to SCs and particular SC types.
      METHODOLOGY/PRINCIPAL FINDINGS: We added value to previously published microarray
      gene expression data by characterizing the promoter type likely to regulate
      transcription. Promoters of up-regulated genes in SCs were characterized in terms
      of alternative promoter (AP) usage and CpG-richness, with the aim of correlating
      features known to affect transcriptional control with SC function. We found that
      SCs have a higher proportion of up-regulated genes using CpG-rich promoters
      compared with the negative controls. Comparing subsets of SC type with the
      controls a slightly different story unfolds. The differences between the
      proliferating adult SCs and the embryonic SCs versus the negative controls are
      statistically significant. Whilst the difference between the quiescent adult SCs
      compared with the negative controls is not. On examination of AP usage, no
      difference was observed between SCs and the controls. However, comparing the
      subsets of SC type with the controls, the quiescent adult SCs are found to up
      regulate a larger proportion of genes that have APs compared to the controls and
      the converse is true for the proliferating adult SCs and the embryonic SCs.
      CONCLUSIONS/SIGNIFICANCE: These findings suggest that looking at features
      associated with control of transcription is a promising future approach for
      characterizing "stemness" and that further investigations of stemness could
      benefit from separate considerations of different SC states. For example,
      "proliferating-stemness" is shown here, in terms of promoter usage, to be
      distinct from "quiescent-stemness".

PMID- 18628963
TI  - Native bacterial endophytes promote host growth in a species-specific manner;
      phytohormone manipulations do not result in common growth responses.
AB  - BACKGROUND: All plants in nature harbor a diverse community of endophytic
      bacteria which can positively affect host plant growth. Changes in plant growth
      frequently reflect alterations in phytohormone homoeostasis by plant-growth
      promoting (PGP) rhizobacteria which can decrease ethylene (ET) levels
      enzymatically by 1-aminocyclopropane-1-carboxylate (ACC) deaminase or produce
      indole acetic acid (IAA). Whether these common PGP mechanisms work similarly for
      different plant species has not been rigorously tested. METHODOLOGY/PRINCIPAL
      FINDINGS: We isolated bacterial endophytes from field-grown Solanum nigrum;
      characterized PGP traits (ACC deaminase activity, IAA production, phosphate
      solubilization and seedling colonization); and determined their effects on their
      host, S. nigrum, as well as on another Solanaceous native plant, Nicotiana
      attenuata. In S. nigrum, a majority of isolates that promoted root growth were
      associated with ACC deaminase activity and IAA production. However, in N.
      attenuata, IAA but not ACC deaminase activity was associated with root growth.
      Inoculating N. attenuata and S. nigrum with known PGP bacteria from a culture
      collection (DSMZ) reinforced the conclusion that the PGP effects are not highly
      conserved. CONCLUSIONS/SIGNIFICANCE: We conclude that natural endophytic bacteria
      with PGP traits do not have general and predictable effects on the growth and
      fitness of all host plants, although the underlying mechanisms are conserved.

PMID- 18628964
TI  - Prelimbic and infralimbic prefrontal cortex interact during fast network
      oscillations.
AB  - BACKGROUND: The medial prefrontal cortex has been implicated in a variety of
      cognitive and executive processes such as decision making and working memory. The
      medial prefrontal cortex of rodents consists of several areas including the
      prelimbic and infralimbic cortex that are thought to be involved in different
      aspects of cognitive performance. Despite the distinct roles in cognitive
      behavior that have been attributed to prelimbic and infralimbic cortex, little is
      known about neuronal network functioning of these areas, and whether these
      networks show any interaction during fast network oscillations.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we show that fast network oscillations in
      rat infralimbic cortex slices occur at higher frequencies and with higher power
      than oscillations in prelimbic cortex. The difference in oscillation frequency
      disappeared when prelimbic and infralimbic cortex were disconnected.
      CONCLUSIONS/SIGNIFICANCE: Our data indicate that neuronal networks of prelimbic
      and infralimbic cortex can sustain fast network oscillations independent of each
      other, but suggest that neuronal networks of prelimbic and infralimbic cortex are
      interacting during these oscillations.

PMID- 18628965
TI  - Differential interactions of the autonomous pathway RRM proteins and chromatin
      regulators in the silencing of Arabidopsis targets.
AB  - We have recently shown that two proteins containing RRM-type RNA-binding domains,
      FCA and FPA, originally identified through their role in flowering time control
      in Arabidopsis, silence transposons and other repeated sequences in the
      Arabidopsis genome. In flowering control, FCA and FPA function in the autonomous
      pathway with conserved chromatin regulators, the histone demethylase FLD and the
      MSI1-homologue FVE, a conserved WD-repeat protein found in many chromatin
      complexes. Here, we investigate how the RRM proteins interact genetically with
      these chromatin regulators at a range of loci in the Arabidopsis genome. We also
      investigate their interaction with the DNA methylation pathway. In several cases
      the RRM protein activity at least partially required a chromatin regulator to
      effect silencing. However, the interactions of the autonomous pathway components
      differed at each target analysed, most likely determined by certain properties of
      the target loci and/or other silencing pathways. We speculate that the RNA
      binding proteins FCA and FPA function as part of a transcriptome surveillance
      mechanism linking RNA recognition with chromatin silencing mechanisms.

PMID- 18628966
TI  - AIP4/Itch regulates Notch receptor degradation in the absence of ligand.
AB  - BACKGROUND: The regulation of Notch signaling heavily relies on ubiquitination
      events. Drosophila Su(dx), a member of the HECT family of ubiquitin-ligases, has
      been described as a negative regulator of Notch signaling, acting on the post
      endocytic sorting of Notch. The mammalian ortholog of Su(dx), Itch/AIP4, has been
      shown to have multiple substrates, including Notch, but the precise events
      regulated by Itch/AIP4 in the Notch pathway have not been identified yet.
      METHODOLOGY/PRINCIPAL FINDINGS: Using Itch-/- fibroblasts expressing the Notch1
      receptor, we show that Itch is not necessary for Notch activation, but rather for
      controlling the degradation of Notch in the absence of ligand. Itch is indeed
      required after the early steps of Notch endocytosis to target it to the lysosomes
      where it is degraded. Furthermore Itch/AIP4 catalyzes Notch polyubiquitination
      through unusual K29-linked chains. We also demonstrate that although Notch is
      associated with Itch/AIP4 in cells, their interaction is not detectable in vitro
      and thus requires either a post-translational modification, or a bridging factor
      that remains to be identified. CONCLUSIONS/SIGNIFICANCE: Taken together our
      results identify a specific step of Notch regulation in the absence of any
      activation and underline differences between mammalian and Drosophila Notch
      pathways.

PMID- 18628967
TI  - Oncogenic BRAF regulates melanoma proliferation through the lineage specific
      factor MITF.
AB  - The Microphthalmia-associated transcription factor (MITF) is an important
      regulator of cell-type specific functions in melanocytic cells. MITF is essential
      for the survival of pigmented cells, but whereas high levels of MITF drive
      melanocyte differentiation, lower levels are required to permit proliferation and
      survival of melanoma cells. MITF is phosphorylated by ERK, and this stimulates
      its activation, but also targets it for degradation through the ubiquitin
      proteosome pathway, coupling MITF degradation to its activation. We have
      previously shown that because ERK is hyper-activated in melanoma cells in which
      BRAF is mutated, the MITF protein is constitutively down-regulated. Here we
      describe another intriguing aspect of MITF regulation by oncogenic BRAF in
      melanoma cells. We show oncogenic BRAF up-regulates MITF transcription through
      ERK and the transcription factor BRN2 (N-Oct3). In contrast, we show that in
      melanocytes this pathway does not exist because BRN2 is not expressed,
      demonstrating that MITF regulation is a newly acquired function of oncogenic BRAF
      that is not performed by the wild-type protein. Critically, in melanoma cells
      MITF is required downstream of oncogenic BRAF because it regulates expression of
      key cell cycle regulatory proteins such as CDK2 and CDK4. Wild-type BRAF does not
      regulate this pathway in melanocytes. Thus, we show that oncogenic BRAF exerts
      exquisite control over MITF on two levels. It downregulates the protein by
      stimulating its degradation, but then counteracts this by increasing
      transcription through BRN2. Our data suggest that oncogenic BRAF plays a critical
      role in regulating MITF expression to ensure that its protein levels are
      compatible with proliferation and survival of melanoma cells. We propose that its
      ability to appropriate the regulation of this critical factor explains in part
      why BRAF is such a potent oncogene in melanoma.

PMID- 18628969
TI  - Impact of clinical preventive services in the ambulatory setting.
AB  - Indicators of the performance of clinical preventive services (CPS) have been
      adopted in the ambulatory setting to improve quality of care. The impact of CPS
      was evaluated in a network of 49 primary care practices providing care to an
      estimated 245,000 adults in the Dallas-Fort Worth area through a sample chart
      review to determine delivery of recommended evidence-based CPS combined with
      medical literature estimates of the effectiveness of CPS. In this population in
      2005, CPS were estimated to have prevented 36 deaths and 97 incident cases of
      cancer; 420 coronary heart disease events (including 66 sudden deaths) and 118
      strokes; 816 cases of influenza and pneumonia (including 24 hospital admissions);
      and 87 osteoporosis-related fractures. Thus, CPS have substantial benefits in
      preventing deaths and illness episodes.

PMID- 18628968
TI  - A bistable gene switch for antibiotic biosynthesis: the butyrolactone regulon in
      Streptomyces coelicolor.
AB  - Many microorganisms, including bacteria of the class Streptomycetes, produce
      various secondary metabolites including antibiotics to gain a competitive
      advantage in their natural habitat. The production of these compounds is highly
      coordinated in a population to expedite accumulation to an effective
      concentration. Furthermore, as antibiotics are often toxic even to their
      producers, a coordinated production allows microbes to first arm themselves with
      a defense mechanism to resist their own antibiotics before production commences.
      One possible mechanism of coordination among individuals is through the
      production of signaling molecules. The gamma-butyrolactone system in Streptomyces
      coelicolor is a model of such a signaling system for secondary metabolite
      production. The accumulation of these signaling molecules triggers antibiotic
      production in the population. A pair of repressor-amplifier proteins encoded by
      scbA and scbR mediates the production and action of one particular gamma
      butyrolactone, SCB1. Based on the proposed interactions of scbA and scbR, a
      mathematical model was constructed and used to explore the ability of this system
      to act as a robust genetic switch. Stability analysis shows that the
      butyrolactone system exhibits bistability and, in response to a threshold SCB1
      concentration, can switch from an OFF state to an ON state corresponding to the
      activation of genes in the cryptic type I polyketide synthase gene cluster, which
      are responsible for production of the hypothetical polyketide. The switching time
      is inversely related to the inducer concentration above the threshold, such that
      short pulses of low inducer concentration cannot switch on the system, suggesting
      its possible role in noise filtering. In contrast, secondary metabolite
      production can be triggered rapidly in a population of cells producing the
      butyrolactone signal due to the presence of an amplification loop in the system.
      S. coelicolor was perturbed experimentally by varying concentrations of SCB1, and
      the model simulations match the experimental data well. Deciphering the
      complexity of this butyrolactone switch will provide valuable insights into how
      robust and efficient systems can be designed using "simple" two-protein networks.

PMID- 18628970
TI  - Emergency department usage by uninsured patients in Galveston County, Texas.
AB  - The number of uninsured Texas residents who rely on the medical emergency
      department as their primary health care provider continues to increase.
      Unfortunately, little information about the characteristics of this group of
      emergency department users is available. Using an administrative billing
      database, we conducted a descriptive study to examine the demographic and
      clinical features of 17,110 consecutive patients without medical insurance who
      presented to the emergency department of the University of Texas Medical Branch
      in Galveston over a 12-month period. We also analyzed the risk of multiple
      emergency department visits or hospitalization according to demographic
      characteristics. Twenty percent of the study population made two or more
      emergency department visits during the study period; 19% of the population was
      admitted to the hospital via the emergency department. The risk of multiple
      emergency department visits was significantly elevated among African Americans
      and increased in a stepwise fashion according to age. The risk of being
      hospitalized was significantly reduced among females, African Americans, and
      Hispanics. There was an age-related monotonic increase in the risk of
      hospitalization. Abdominal pain, cellulitis, and spinal disorders were the most
      common primary diagnoses in patients who made multiple emergency department
      visits. Hospitalization occurred most frequently in patients with a primary
      diagnosis of chest pain, nonischemic heart disease, or an affective disorder.
      Additional studies of emergency department usage by uninsured patients from other
      regions of Texas are warranted. Such data may prove helpful in developing
      effective community-based alternatives to the emergency department for this
      growing segment of our population. Local policymakers who are responsible for the
      development of safety net programs throughout the state should find this
      information particularly useful.

PMID- 18628971
TI  - Serum nutrient deficiencies in the patient with complex temporomandibular joint
      problems.
AB  - This study evaluated serum nutrients in 23 patients who had previous
      Proplast/Teflon implants to their temporomandibular joints (TMJ) and continued to
      remain in chronic, severe, irresolvable pain despite subsequent surgical
      reconstruction. All of the patients were women, and their average age was 40.6
      years (range, 28-55 years). Standard blood assays were performed for beta
      carotene (vitamin A), folate, serum iron, ferritin, zinc, magnesium, and vitamins
      B1, B6, B12, and C. Each patient was deficient in at least one of these 10
      elements, with an average of 3.3 elements. Some factors that may be responsible
      for the deficiency state include inadequate nutritional intake, malabsorption,
      utilization dysfunction, increased requirements, or drug interactions. In
      conclusion, the patient who has had multiple, complex TMJ operations with a
      history of TMJ Proplast/Teflon implants and poor treatment results may be
      suffering from an unrecognized malnutrition state, substantially adding to the
      patient's morbidity. Nutritional evaluations, dietary counseling, and appropriate
      medical management may improve the treatment outcomes for these patients.

PMID- 18628972
TI  - Autologous fat grafts placed around temporomandibular joint total joint
      prostheses to prevent heterotopic bone formation.
AB  - This study evaluated 1) the efficacy of packing autologous fat grafts around
      temporomandibular joint (TMJ) total joint prosthetic reconstructions to prevent
      fibrosis and heterotopic bone formation and 2) the effects on postsurgical joint
      mobility and jaw function. One hundred fifteen patients (5 males and 110 females)
      underwent TMJ reconstruction with total joint prostheses and simultaneous fat
      grafts (88 bilateral and 27 unilateral) for a total of 203 joints. The abdominal
      fat grafts were packed around the articulating portion of the joint prostheses
      after the fossa and mandibular components were stabilized. Patients were divided
      into two groups: group 1 (n = 76 joints) received Christensen total joint
      prostheses, and group 2 (n = 127 joints) received TMJ Concepts total joint
      prostheses. Clinical and radiographic assessments were performed before surgery,
      immediately after surgery, and at long-term follow-up. In group 1, maximal
      incisal opening (MIO) increased 3.5 mm, lateral excursions (LE) decreased 0.2 mm,
      and jaw function improved 1.9 levels. In group 2, MIO increased 6.8 mm, LE
      decreased 1.4 mm, and jaw function improved 2.4 levels. The improvement for MIO
      and patient perception of jaw function in both groups was statistically
      significant; no significant difference was found for LE. There was no
      radiographic or clinical evidence of heterotopic calcifications or limitation of
      mobility secondary to fibrosis in either group. Twenty-five Christensen
      prostheses (33%) were removed because of device failure and/or metal
      hypersensitivity; no fibrosis or heterotopic bone formation was seen at surgical
      removal. Four TMJ Concepts prostheses (3%) were removed because of metal
      hypersensitivity. In all instances, removal of the prostheses was unrelated to
      the autologous fat grafting. Ten patients (8.7%) developed complications
      involving the fat donor site: two patients (1.8%) developed abdominal cysts
      requiring surgery, and eight patients (6.9%) developed seroma formation requiring
      aspiration. Autologous fat transplantation is a useful adjunct to prosthetic TMJ
      reconstruction to minimize the occurrence of excessive joint fibrosis and
      heterotopic calcification, consequently providing improved range of motion and
      jaw function.

PMID- 18628973
TI  - Multidisciplinary treatment of a large cerebral dural arteriovenous fistula using
      embolization, surgery, and radiosurgery.
AB  - Dural arteriovenous fistulae are rare lesions composed of abnormal connections
      between meningeal arteries and the dural sinuses or lepto-meningeal veins.
      Treatment is challenging because of the small size and wide distribution of the
      myriad sites of fistulous connection. We present a case of a dural arteriovenous
      fistula presenting with visual deterioration, pulsatile tinnitus, and
      intracranial hypertension that was successfully treated with a multidisciplinary
      approach combining angiographic, surgical, and radiosurgical intervention. This
      is one of the largest of these formidable lesions treated in this fashion that
      has been reported.

PMID- 18628974
TI  - Amelioration of streptozotocin-induced diabetes in mice with cells derived from
      human marrow stromal cells.
AB  - BACKGROUND: Pluri-potent bone marrow stromal cells (MSCs) provide an attractive
      opportunity to generate unlimited glucose-responsive insulin-producing cells for
      the treatment of diabetes. We explored the potential for human MSCs (hMSCs) to be
      differentiated into glucose-responsive cells through a non-viral genetic
      reprogramming approach. METHODS AND FINDINGS: Two HMSC lines were transfected
      with three genes: PDX-1, NeuroD1 and Ngn3 without subsequent selection, followed
      by differentiation induction in vitro and transplantation into diabetic mice.
      Human MSCs expressed mRNAs of the archetypal stem cell markers: Sox2, Oct4, Nanog
      and CD34, and the endocrine cell markers: PDX-1, NeuroD1, Ngn3, and Nkx6.1.
      Following gene transfection and differentiation induction, hMSCs expressed
      insulin in vitro, but were not glucose regulated. After transplantation, hMSCs
      differentiated further and approximately 12.5% of the grafted cells expressed
      insulin. The graft bearing kidneys contained mRNA of insulin and other key genes
      required for the functions of beta cells. Mice transplanted with manipulated
      hMSCs showed reduced blood glucose levels (from 18.9+/-0.75 to 7.63+/-1.63 mM).
      13 of the 16 mice became normoglycaemic (6.9+/-0.64 mM), despite the failure to
      detect the expression of SUR1, a K(+)-ATP channel component required for
      regulation of insulin secretion. CONCLUSIONS: Our data confirm that hMSCs can be
      induced to express insulin sufficient to reduce blood glucose in a diabetic mouse
      model. Our triple gene approach has created cells that seem less glucose
      responsive in vitro but which become more efficient after transplantation. The
      maturation process requires further study, particularly the in vivo factors
      influencing the differentiation, in order to scale up for clinical purposes.

PMID- 18628976
TI  - Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of
      principle study.
AB  - BACKGROUND: Epigenetic changes are emerging as one of the most important events
      in carcinogenesis. Two alterations in the pattern of DNA methylation in breast
      cancer (BC) have been previously reported; active estrogen receptor-alpha (ER
      alpha) is associated with decreased methylation of ER-alpha target (ERT) genes,
      and polycomb group target (PCGT) genes are more likely than other genes to have
      promoter DNA hypermethylation in cancer. However, whether DNA methylation in
      normal unrelated cells is associated with BC risk and whether these imprints can
      be related to factors which can be modified by the environment, is unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative methylation analysis in a case
      control study (n = 1,083) we found that DNA methylation of peripheral blood cell
      DNA provides good prediction of BC risk. We also report that invasive ductal and
      invasive lobular BC is characterized by two different sets of genes, the latter
      particular by genes involved in the differentiation of the mesenchyme (PITX2,
      TITF1, GDNF and MYOD1). Finally we demonstrate that only ERT genes predict ER
      positive BC; lack of peripheral blood cell DNA methylation of ZNF217 predicted BC
      independent of age and family history (odds ratio 1.49; 95% confidence interval
      1.12-1.97; P = 0.006) and was associated with ER-alpha bioactivity in the
      corresponding serum. CONCLUSION/SIGNIFICANCE: This first large-scale
      epigenotyping study demonstrates that DNA methylation may serve as a link between
      the environment and the genome. Factors that can be modulated by the environment
      (like estrogens) leave an imprint in the DNA of cells that are unrelated to the
      target organ and indicate the predisposition to develop a cancer. Further
      research will need to demonstrate whether DNA methylation profiles will be able
      to serve as a new tool to predict the risk of developing chronic diseases with
      sufficient accuracy to guide preventive measures.

PMID- 18628975
TI  - Histone deacetylases control neurogenesis in embryonic brain by inhibition of
      BMP2/4 signaling.
AB  - BACKGROUND: Histone-modifying enzymes are essential for a wide variety of
      cellular processes dependent upon changes in gene expression. Histone
      deacetylases (HDACs) lead to the compaction of chromatin and subsequent silencing
      of gene transcription, and they have recently been implicated in a diversity of
      functions and dysfunctions in the postnatal and adult brain including ocular
      dominance plasticity, memory consolidation, drug addiction, and depression. Here
      we investigate the role of HDACs in the generation of neurons and astrocytes in
      the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in
      differentiating neural progenitor cells, we have taken a pharmacological approach
      to inhibit multiple family members. Inhibition of class I and II HDACs in
      developing mouse embryos with trichostatin A resulted in a dramatic reduction in
      neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in
      the cortex. An identical effect was observed upon pharmacological inhibition of
      HDACs in in vitro-differentiating neural precursors derived from the same brain
      regions. A reduction in neurogenesis in ganglionic eminence-derived neural
      precursors was accompanied by an increase in the production of immature
      astrocytes. We show that HDACs control neurogenesis by inhibition of the bone
      morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs
      function at the transcriptional level by inhibiting and promoting, respectively,
      the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling.
      Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis
      and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in
      which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a
      transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and
      in vitro that is critical for neurogenesis in the ganglionic eminences and that
      modulates cortical neurogenesis. The results also suggest that HDACs may regulate
      the developmental switch from neurogenesis to astrogliogenesis that occurs in
      late gestation.

PMID- 18628977
TI  - Direct infection and replication of naturally occurring hepatitis C virus
      genotypes 1, 2, 3 and 4 in normal human hepatocyte cultures.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection afflicts about 170 million
      individuals worldwide. However, the HCV life cycle is only partially understood
      because it has not been possible to infect normal human hepatocytes in culture.
      The current Huh-7 systems use cloned, synthetic HCV RNA expressed in
      hepatocellular carcinoma cells to produce virions, but these cells cannot be
      infected with naturally occurring HCV obtained from infected patients.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a human hepatocyte culture
      permissible to the direct infection with naturally occurring HCV genotypes 1, 2,
      3 and 4 in the blood of HCV-infected patients. The culture system mimics the
      biology and kinetics of HCV infection in humans, and produces infectious virions
      that can infect naive human hepatocytes. CONCLUSIONS/SIGNIFICANCE: This culture
      system should complement the existing systems, and may facilitate the
      understanding of the HCV life cycle, its effects in the natural host cell, the
      hepatocyte, as well as the development of novel therapeutics and vaccines.

PMID- 18628978
TI  - High throughput automated allele frequency estimation by pyrosequencing.
AB  - Pyrosequencing is a DNA sequencing method based on the principle of sequencing-by
      synthesis and pyrophosphate detection through a series of enzymatic reactions.
      This bioluminometric, real-time DNA sequencing technique offers unique
      applications that are cost-effective and user-friendly. In this study, we have
      combined a number of methods to develop an accurate, robust and cost efficient
      method to determine allele frequencies in large populations for association
      studies. The assay offers the advantage of minimal systemic sampling errors, uses
      a general biotin amplification approach, and replaces dTTP for dATP-apha-thio to
      avoid non-uniform higher peaks in order to increase accuracy. We demonstrate that
      this newly developed assay is a robust, cost-effective, accurate and reproducible
      approach for large-scale genotyping of DNA pools. We also discuss potential
      improvements of the software for more accurate allele frequency analysis.

PMID- 18628979
TI  - The polycomb repressive complex 2 is a potential target of SUMO modifications.
AB  - BACKGROUND: The Polycomb Repressive Complex 2 (PRC2) functions as a
      transcriptional repressor through a mechanism that involves methylation of
      Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular
      proliferation, development, and cell fate decisions. PRC2 target genes include
      important regulators of development and proliferation as well as tumor suppressor
      genes. Consistent with this, the activity of several Polycomb group (PcG)
      proteins is deregulated in human cancer suggesting an important role for PcGs in
      tumor development. Whereas the downstream functions of PcGs are well
      characterized, the mechanisms of their recruitment to target genes and the
      regulation of their activity are not fully understood. PRINCIPAL FINDINGS: Here
      we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and
      in vivo. Among several putative sumoylation sites we have mapped the major site
      of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2
      conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12
      sumoylation site does not abolish this binding. Finally, we provide evidence that
      the E3-ligase PIASXbeta interacts and enhances the sumoylation of SUZ12 in vivo
      suggesting that PIASXbeta could function as an E3-ligase for SUZ12. CONCLUSIONS:
      Taken together, our data identify sumoylation as a novel post-translational
      modification of components of the PRC2 complex, which could suggest a potential
      new mechanism to modulate PRC2 repressive activity. Further work aimed to
      identify the physiological conditions for these modifications will be required to
      understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic
      regulation of transcription.

PMID- 18628980
TI  - Implication of new WHO growth standards on identification of risk factors and
      estimated prevalence of malnutrition in rural Malawian infants.
AB  - BACKGROUND: The World Health Organization (WHO) released new Child Growth
      Standards in 2006 to replace the current National Center for Health Statistics
      (NCHS) growth reference. We assessed how switching from the NCHS to the newly
      released WHO Growth Standards affects the estimated prevalence of wasting,
      underweight and stunting, and the pattern of risk factors identified.
      METHODOLOGY/PRINCIPAL FINDINGS: Data were drawn from a village-informant driven
      Demographic Surveillance System in Northern Malawi. Children (n = 1328) were
      visited twice at 0-4 months and 11-15 months. Data were collected on the
      demographic and socio-economic environment of the child, health history, maternal
      and child anthropometry and child feeding practices. Weight-for-length, weight
      for-age and length-for-age were derived in z-scores using the two growth
      references. In early infancy, prevalence estimates were 2.9, 6.1, and 8.5 fold
      higher for stunting, underweight, and wasting respectively using the WHO
      standards compared to NCHS reference (p<0.001 for all). At one year, prevalence
      estimates for wasting and stunting did not differ significantly according to
      reference used, but the prevalence of underweight was half that with the NCHS
      reference (p<0.001). Patterns of risk factors were similar with the two growth
      references for all outcomes at one year although the strength of association was
      higher with WHO standards. CONCLUSIONS/SIGNIFICANCE: Differences in prevalence
      estimates differed in magnitude but not direction from previous studies. The
      scale of these differences depends on the population's nutritional status thus it
      should not be assumed a priori. The increase in estimated prevalence of wasting
      in early infancy has implications for feeding programs targeting lactating
      mothers and ante-natal multiple micronutrients supplementation to tackle small
      birth size. Risk factors identified using WHO standards remain comparable with
      findings based on the NCHS reference in similar settings. Further research should
      aim to identify whether the young infants additionally diagnosed as malnourished
      by this new standard are more appropriate targets for interventions than those
      identified with the NCHS reference.

PMID- 18628981
TI  - Monocytes from cystic fibrosis patients are locked in an LPS tolerance state:
      down-regulation of TREM-1 as putative underlying mechanism.
AB  - Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from
      abnormalities in the gene that codes for the chloride channel, Cystic Fibrosis
      Transmembrane Conductance Regulator (CFTR). CF patients are frequently colonized
      by several pathogens, but the mechanisms that allow colonization in spite of
      apparently functional immune systems are incompletely understood. In this paper
      we show that blood peripheral monocytes isolated from CF patients are found in an
      endotoxin tolerance state, yet this is not due to a deficient TLR activation. On
      the other hand, levels of the amplifier of inflammatory responses, TREM-1
      (Triggering Receptor Expressed on Myeloid cells), are notably down-regulated in
      monocytes from patients, in comparison to those extracted from healthy
      volunteers. Furthermore, the soluble form of TREM-1 (sTREM-1) was not detected in
      the sera of patients. Additionally, and in strict contrast to patients who suffer
      from Chronic Obstructive Pulmonary Disease (COPD), CF monocytes challenged ex
      vivo with LPS neither up-regulated membrane-anchored TREM-1 nor sTREM-1. Finally,
      similar levels of PGE(2) expression and p65 translocation into the nucleus were
      found in both patients and healthy volunteers, thus suggesting that TREM-1
      regulation is neither controlled by PGE(2) levels nor by p65 activation in this
      case. However, PU.1 translocation into the nucleus was significantly higher in CF
      monocytes than in controls, suggesting a role for this transcription factor in
      the control of TREM-1 expression. We conclude that down-regulation of TREM-1
      expression in cystic fibrosis patients is at least partly responsible for the
      endotoxin tolerance state in which their monocytes are locked.

PMID- 18628982
TI  - Identification of a regulatory T cell specific cell surface molecule that
      mediates suppressive signals and induces Foxp3 expression.
AB  - Regulatory T (T(reg)) cells control immune activation and maintain tolerance. How
      T(regs) mediate their suppressive function is unclear. Here we identified a cell
      surface molecule, called GARP, (or LRRC32), which within T cells is specifically
      expressed in T(regs) activated through the T cell receptor (TCR). Ectopic
      expression of GARP in human naive T (T(N)) cells inhibited their proliferation
      and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in
      T(N) cells induced expression of T(reg) master transcription factor Foxp3 and
      endowed them with a partial suppressive function. The extracellular but not the
      cytoplasmic region of GARP, was necessary for these functions. Silencing Foxp3 in
      human T(reg) cells reduced expression of GARP and attenuated their suppressive
      function. However, GARP function was not affected when Foxp3 was downregulated in
      GARP-overexpressing cells, while silencing GARP in Foxp3-overexpressing cells
      reduced their suppressive activity. These findings reveal a novel cell surface
      molecule-mediated regulatory mechanism, with implications for modulating aberrant
      immune responses.

PMID- 18628983
TI  - Influenza virus in human exhaled breath: an observational study.
AB  - BACKGROUND: Recent studies suggest that humans exhale fine particles during tidal
      breathing but little is known of their composition, particularly during
      infection. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a study of influenza
      infected patients to characterize influenza virus and particle concentrations in
      their exhaled breath. Patients presenting with influenza-like-illness, confirmed
      influenza A or B virus by rapid test, and onset within 3 days were recruited at
      three clinics in Hong Kong, China. We collected exhaled breath from each subject
      onto Teflon filters and measured exhaled particle concentrations using an optical
      particle counter. Filters were analyzed for influenza A and B viruses by
      quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test
      positive patients provided exhaled breath filter samples (7 subjects infected
      with influenza B virus and 5 subjects infected with influenza A virus). We
      detected influenza virus RNA in the exhaled breath of 4 (33%) subjects--three
      (60%) of the five patients infected with influenza A virus and one (14%) of the
      seven infected with influenza B virus. Exhaled influenza virus RNA generation
      rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87%
      of particles exhaled were under 1 microm in diameter. CONCLUSIONS: These findings
      regarding influenza virus RNA suggest that influenza virus may be contained in
      fine particles generated during tidal breathing, and add to the body of
      literature suggesting that fine particle aerosols may play a role in influenza
      transmission.

PMID- 18628984
TI  - Nerve growth factor stimulates interaction of Cayman ataxia protein BNIP
      H/Caytaxin with peptidyl-prolyl isomerase Pin1 in differentiating neurons.
AB  - Mutations in ATCAY that encodes the brain-specific protein BNIP-H (or Caytaxin)
      lead to Cayman cerebellar ataxia. BNIP-H binds to glutaminase, a neurotransmitter
      producing enzyme, and affects its activity and intracellular localization. Here
      we describe the identification and characterization of the binding between BNIP-H
      and Pin1, a peptidyl-prolyl cis/trans isomerase. BNIP-H interacted with Pin1
      after nerve growth factor-stimulation and they co-localized in the neurites and
      cytosol of differentiating pheochromocytoma PC12 cells and the embryonic
      carcinoma P19 cells. Deletional mutagenesis revealed two cryptic binding sites
      within the C-terminus of BNIP-H such that single point mutants affecting the WW
      domain of Pin1 completely abolished their binding. Although these two sites do
      not contain any of the canonical Pin1-binding motifs they showed differential
      binding profiles to Pin1 WW domain mutants S16E, S16A and W34A, and the
      catalytically inert C113A of its isomerase domain. Furthermore, their direct
      interaction would occur only upon disrupting the ability of BNIP-H to form an
      intramolecular interaction by two similar regions. Furthermore, expression of
      Pin1 disrupted the BNIP-H/glutaminase complex formation in PC12 cells under nerve
      growth factor-stimulation. These results indicate that nerve growth factor may
      stimulate the interaction of BNIP-H with Pin1 by releasing its intramolecular
      inhibition. Such a mechanism could provide a post-translational regulation on the
      cellular activity of BNIP-H during neuronal differentiation.

PMID- 18628985
TI  - Molecular characterization of the gastrula in the turtle Emys orbicularis: an
      evolutionary perspective on gastrulation.
AB  - Due to the presence of a blastopore as in amphibians, the turtle has been
      suggested to exemplify a transition form from an amphibian- to an avian-type
      gastrulation pattern. In order to test this hypothesis and gain insight into the
      emergence of the unique characteristics of amniotes during gastrulation, we have
      performed the first molecular characterization of the gastrula in a reptile, the
      turtle Emys orbicularis. The study of Brachyury, Lim1, Otx2 and Otx5 expression
      patterns points to a highly conserved dynamic of expression with amniote model
      organisms and makes it possible to identify the site of mesoderm internalization,
      which is a long-standing issue in reptiles. Analysis of Brachyury expression also
      highlights the presence of two distinct phases, less easily recognizable in model
      organisms and respectively characterized by an early ring-shaped and a later
      bilateral symmetrical territory. Systematic comparisons with tetrapod model
      organisms lead to new insights into the relationships of the
      blastopore/blastoporal plate system shared by all reptiles, with the blastopore
      of amphibians and the primitive streak of birds and mammals. The biphasic
      Brachyury expression pattern is also consistent with recent models of emergence
      of bilateral symmetry, which raises the question of its evolutionary
      significance.

PMID- 18628986
TI  - Relationship between transmission intensity and incidence of dengue hemorrhagic
      fever in Thailand.
AB  - BACKGROUND: Dengue is the most prevalent mosquito-borne virus, and potentially
      fatal dengue hemorrhagic fever (DHF) occurs mainly in secondary infections. It
      recently was hypothesized that, due to the presence of cross-immunity, the
      relationship between the incidence of DHF and transmission intensity may be
      negative at areas of intense transmission. We tested this hypothesis empirically,
      using vector abundance as a surrogate of transmission intensity.
      METHODOLOGY/PRINCIPAL FINDINGS: House Index (HI), which is defined as the
      percentage of households infested with vector larvae/pupae, was obtained from
      surveys conducted on one million houses in Thailand, between 2002 and 2004.
      First, the utility of HI as a surrogate of transmission intensity was confirmed
      because HI was correlated negatively with mean age of DHF in the population.
      Next, the relationship between DHF incidence and HI was investigated. DHF
      incidence increased only up to an HI of about 30, but declined thereafter.
      Reduction of HI from the currently maximal level to 30 would increase the
      incidence by more than 40%. Simulations, which implemented a recently proposed
      model for cross-immunity, generated results that resembled actual epidemiological
      data. It was predicted that cross-immunity generates a wide variation in
      incidence, thereby obscuring the relationship between incidence and transmission
      intensity. The relationship would become obvious only if data collected over a
      long duration (e.g., >10 years) was averaged. CONCLUSION: The negative
      relationship between DHF incidence and dengue transmission intensity implies that
      in regions of intense transmission, insufficient reduction of vector abundance
      may increase long-term DHF incidence. Further studies of a duration much longer
      than the present study, are warranted.

PMID- 18628987
TI  - Role of secreted conjunctival mucosal cytokine and chemokine proteins in
      different stages of trachomatous disease.
AB  - BACKGROUND: Chlamydia trachomatis is responsible for trachoma, the primary cause
      of preventable blindness worldwide. Plans to eradicate trachoma using the World
      Health Organization's SAFE program (Surgery, Antibiotics, Facial Cleanliness and
      Environment Improvement) have resulted in recurrence of infection and disease
      following cessation of treatment in many endemic countries, suggesting the need
      for a vaccine to control infection and trachomatous disease. Vaccine development
      requires, in part, knowledge of the mucosal host immune responses in both healthy
      and trachomatous conjuctivae-an area of research that remains insufficiently
      studied. METHODOLOGY/PRINCIPAL FINDINGS: We characterized 25 secreted cytokines
      and chemokines from the conjunctival mucosa of individuals residing in a trachoma
      endemic region of Nepal using Luminex X100 multiplexing technology.
      Immunomodulating effects of concurrent C. trachomatis infection were also
      examined. We found that proinflammatory cytokines IL-1beta (r = 0.259, P = 0.001)
      and TNFalpha (r = 0.168, P<0.05) were significantly associated with trachomatous
      disease and concurrent C. trachomatis infection compared with age and sex matched
      controls from the same region who did not have trachoma. In support of these
      findings, anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) was
      negatively associated with chronic scarring trachoma (r = -0.249, P = 0.001).
      Additional cytokines (Th1, IL-12p40 [r = -0.212, P<0.01], and Th2, IL-4 and IL-13
      [r = -0.165 and -0.189, respectively, P<0.05 for both]) were negatively
      associated with chronic scarring trachoma, suggesting a protective role.
      Conversely, a pathogenic role for the Th3/Tr1 cytokine IL-10 (r = 0.180, P<0.05)
      was evident with increased levels for all trachoma grades. New risk factors for
      chronic scarring trachoma included IL-6 and IL-15 (r = 0.259 and 0.292,
      respectively, P<0.005 for both) with increased levels for concurrent C.
      trachomatis infections (r = 0.206, P<0.05, and r = 0.304, P<0.005, respectively).
      Chemokine protein levels for CCL11 (Eotaxin), CXCL8 (IL-8), CXCL9 (MIG), and CCL2
      (MCP-1) were elevated in chronic scarring trachoma compared with age and sex
      matched controls (P<0.05, for all). CONCLUSIONS/SIGNIFICANCE: Our quantitative
      detection of previously uncharacterized and partially characterized cytokines, a
      soluble cytokine receptor, and chemokines for each trachoma grade and
      associations with C. trachomatis infections provide, to date, the most
      comprehensive immunologic evaluation of trachoma. These findings highlight novel
      pathologic and protective factors involved in trachomatous disease, which will
      aid in designing immunomodulating therapeutics and a vaccine.

PMID- 18628988
TI  - Neither replication nor simulation supports a role for the axon guidance pathway
      in the genetics of Parkinson's disease.
AB  - Susceptibility to sporadic Parkinson's disease (PD) is thought to be influenced
      by both genetic and environmental factors and their interaction with each other.
      Statistical models including multiple variants in axon guidance pathway genes
      have recently been purported to be capable of predicting PD risk, survival free
      of the disease and age at disease onset; however the specific models have not
      undergone independent validation. Here we tested the best proposed risk panel of
      23 single nucleotide polymorphisms (SNPs) in two PD sample sets, with a total of
      525 cases and 518 controls. By single marker analysis, only one marker was
      significantly associated with PD risk in one of our sample sets (rs6692804: P =
      0.03). Multi-marker analysis using the reported model found a mild association in
      one sample set (two sided P = 0.049, odds ratio for each score change = 1.07) but
      no significance in the other (two sided P = 0.98, odds ratio = 1), a stark
      contrast to the reported strong association with PD risk (P = 4.64x10(-38), odds
      ratio as high as 90.8). Following a procedure similar to that used to build the
      reported model, simulated multi-marker models containing SNPs from randomly
      chosen genes in a genome wide PD dataset produced P-values that were highly
      significant and indistinguishable from similar models where disease status was
      permuted (3.13x10(-23) to 4.90x10(-64)), demonstrating the potential for
      overfitting in the model building process. Together, these results challenge the
      robustness of the reported panel of genetic markers to predict PD risk in
      particular and a role of the axon guidance pathway in PD genetics in general.

PMID- 18628989
TI  - UV-light exposed prion protein fails to form amyloid fibrils.
AB  - Amyloid fibril formation involves three steps; structural perturbation,
      nucleation and elongation. We have investigated amyloidogenesis using prion
      protein as a model system and UV-light as a structural perturbant. We find that
      UV-exposed prion protein fails to form amyloid fibrils. Interestingly, if
      provided with pre-formed fibrils as seeds, UV-exposed prion protein formed
      amyloid fibrils albeit with slightly different morphology. Atomic force
      microscopy and electron microscopic studies clearly show the formation of fibrils
      under these conditions. Circular dichroism study shows loss in helicity in UV
      exposed protein. UV-exposed prion protein fails to form amyloid fibrils. However,
      it remains competent for fibril extension, suggesting that UV-exposure results in
      loss of nucleating capability. This work opens up possibility of segregating
      nucleation and elongation step of amyloidogenesis, facilitating screening of new
      drug candidates for specifically inhibiting either of these processes. In
      addition, the work also highlights the importance of light-induced structural and
      functional alterations which are important in protein based therapeutics.

PMID- 18628990
TI  - Structure-activity relationship and substrate-dependent phenomena in effects of
      ginsenosides on activities of drug-metabolizing P450 enzymes.
AB  - Ginseng, a traditional herbal medicine, may interact with several co-administered
      drugs in clinical settings, and ginsenosides, the major active components of
      ginseng, may be responsible for these ginseng-drug interactions (GDIs). Results
      from previous studies on ginsenosides' effects on human drug-metabolizing P450
      enzymes are inconsistent and confusing. Herein, we first evaluated the inhibitory
      effects of fifteen ginsenosides and sapogenins on human CYP1A2, CYP2C9, CYP2C19,
      CYP2D6 and CYP3A4 enzymes by using commercially available fluorescent probes. The
      structure-activity relationship of their effects on the P450s was also explored
      and a pharmacophore model was established for CYP3A4. Moreover, substrate
      dependent phenomena were found in ginsenosides' effects on CYP3A4 when another
      fluorescent probe was used, and were further confirmed in tests with conventional
      drug probes and human liver microsomes. These substrate-dependent effects of the
      ginsenosides may provide an explanation for the inconsistent results obtained in
      previous GDI reports.

PMID- 18628991
TI  - Advances in quantitative hepcidin measurements by time-of-flight mass
      spectrometry.
AB  - Assays for the detection of the iron regulatory hormone hepcidin in plasma or
      urine have not yet been widely available, whereas quantitative comparisons
      between hepcidin levels in these different matrices were thus far even impossible
      due to technical restrictions. To circumvent these limitations, we here describe
      several advances in time-of flight mass spectrometry (TOF MS), the most important
      of which concerned spiking of a synthetic hepcidin analogue as internal standard
      into serum and urine samples. This serves both as a control for experimental
      variation, such as recovery and matrix-dependent ionization and ion suppression,
      and at the same time allows value assignment to the measured hepcidin peak
      intensities. The assay improvements were clinically evaluated using samples from
      various patients groups and its relevance was further underscored by the
      significant correlation of serum hepcidin levels with serum iron indices in
      healthy individuals. Most importantly, this approach allowed kinetic studies as
      illustrated by the paired analyses of serum and urine samples, showing that more
      than 97% of the freely filtered serum hepcidin can be reabsorbed in the kidney.
      Thus, the here reported advances in TOF MS-based hepcidin measurements represent
      critical steps in the accurate quantification of hepcidin in various body fluids
      and pave the way for clinical studies on the kinetic behavior of hepcidin in both
      healthy and diseased states.

PMID- 18628992
TI  - Evaluating the influence of epidemiological parameters and host ecology on the
      spread of phocine distemper virus through populations of harbour seals.
AB  - BACKGROUND: Outbreaks of phocine distemper virus (PDV) in Europe during 1988 and
      2002 were responsible for the death of around 23,000 and 30,000 harbour seals,
      respectively. These epidemics, particularly the one in 2002, provided an unusual
      opportunity to estimate epidemic parameters for a wildlife disease. There were
      marked regional differences in the values of some parameters both within and
      between epidemics. METHODOLOGY AND PRINCIPAL FINDINGS: We used an individual
      based model of seal movement that allowed us to incorporate realistic
      representations of space, time and animal behaviour into a traditional
      epidemiological modelling framework. We explored the potential influence of a
      range of ecological (foraging trip duration, time of epidemic onset, population
      size) and epidemiological (length of infectious period, contact rate between
      infectious and susceptible individuals, case mortality) parameters on four
      readily-measurable epidemic characteristics (number of dead individuals, duration
      of epidemic, peak mortality date and prevalence) and on the probability that an
      epidemic would occur in a particular region. We analysed the outputs as if they
      were the results of a series of virtual experiments, using Generalised Linear
      Modelling. All six variables had a significant effect on the probability that an
      epidemic would be recognised as an unusual mortality event by human observers.
      CONCLUSIONS: Regional and temporal variation in contact rate was the most likely
      cause of the observed differences between the two epidemics. This variation could
      be a consequence of differences in the way individuals divide their time between
      land and sea at different times of the year.

PMID- 18628993
TI  - Immunological monitoring of renal transplant recipients to predict acute
      allograft rejection following the discontinuation of tacrolimus.
AB  - BACKGROUND: Transplant patients would benefit from reduction of immunosuppression
      providing that graft rejection is prevented. We have evaluated a number of
      immunological markers in blood of patients in whom tacrolimus was withdrawn after
      renal transplantation. The alloreactive precursor frequency of CD4+ and CD8+ T
      cells, the frequency of T cell subsets and the functional capacity of
      CD4+CD25+FoxP3+ regulatory T cells (Treg) were analyzed before transplantation
      and before tacrolimus reduction. In a case-control design, the results were
      compared between patients with (n = 15) and without (n = 28) acute rejection
      after tacrolimus withdrawal. PRINCIPAL FINDINGS: Prior to tacrolimus reduction,
      the ratio between memory CD8+ T cells and Treg was higher in rejectors compared
      to non-rejectors. Rejectors also had a higher ratio between memory CD4+ T cells
      and Treg, and ratios <20 were only observed in non-rejectors. Between the time of
      transplantation and the start of tacrolimus withdrawal, an increase in naive T
      cell frequencies and a reciprocal decrease of effector T cell percentages was
      observed in rejectors. The proportion of Treg within the CD4+ T cells decreased
      after transplantation, but anti-donor regulatory capacity of Treg remained
      unaltered in rejectors and non-rejectors. CONCLUSIONS: Immunological monitoring
      revealed an association between acute rejection following the withdrawal of
      tacrolimus and 1) the ratio of memory T cells and Treg prior to the start of
      tacrolimus reduction, and 2) changes in the distribution of naive, effector and
      memory T cells over time. Combination of these two biomarkers allowed highly
      specific identification of patients in whom immunosuppression could be safely
      reduced.

PMID- 18628994
TI  - Identification of a neuropeptide S responsive circuitry shaping amygdala activity
      via the endopiriform nucleus.
AB  - Neuropeptide S (NPS) and its receptor are thought to define a set of specific
      brain circuits involved in fear and anxiety. Here we provide evidence for a
      novel, NPS-responsive circuit that shapes neural activity in the mouse
      basolateral amygdala (BLA) via the endopiriform nucleus (EPN). Using slice
      preparations, we demonstrate that NPS directly activates an inward current in 20%
      of EPN neurons and evokes an increase of glutamatergic excitation in this
      nucleus. Excitation of the EPN is responsible for a modulation of BLA activity
      through NPS, characterized by a general increase of GABAergic inhibition and
      enhancement of spike activity in a subset of BLA projection neurons. Finally,
      local injection of NPS to the EPN interferes with the expression of contextual,
      but not auditory cued fear memory. Together, these data suggest the existence of
      a specific NPS-responsive circuitry between EPN and BLA, likely involved in
      contextual aspects of fear memory.

PMID- 18628995
TI  - Modulation of NKT cell development by B7-CD28 interaction: an expanding horizon
      for costimulation.
AB  - It has been demonstrated that the development of NKT cells requires CD1d. The
      contribution of costimulatory molecules in this process has not been studied.
      Here we show that in mice with targeted mutations of B7-1/2 and CD28, the
      TCRbeta(+)alpha-Galcer/CD1d(+) (iValpha14 NKT) subset is significantly reduced in
      the thymus, spleen and liver. This is mainly due to decreased cell proliferation;
      although increased cell death in the thymi of CD28-deficient mice was also
      observed. Moreover, in the B7-1/2- and CD28-deficient mice, we found a decreased
      percentage of the CD4(-)NK1.1(+) subset and a correspondingly increased portion
      of the CD4(+)NK1.1(-) subset. In addition, the mice with a targeted mutation of
      either B7 or CD28 had a reduced susceptibility to Con A induced hepatitis, which
      is known to be mediated by NKT cells. Our results demonstrate that the
      development, maturation and function of NKT cell are modulated by the
      costimulatory pathway and thus expand the horizon of costimulation into NKT,
      which is widely viewed as a bridge between innate and adaptive immunity. As such,
      costimulation may modulate all major branches of cell-mediated immunity,
      including T cells, NK cells and NKT cells.

PMID- 18628996
TI  - Defects in actin dynamics lead to an autoinflammatory condition through the
      upregulation of CXCL5.
AB  - BACKGROUND: Destrin (DSTN) is a member of the ADF/cofilin family of proteins and
      is an important regulator of actin dynamics. The primary function of destrin is
      to depolymerize filamentous actin into its monomeric form and promote filament
      severing. While progress has been made in understanding the biochemical functions
      of the ADF/cofilin proteins, the study of an animal model for cells deficient for
      DSTN provides an opportunity to investigate the physiological processes regulated
      by proper actin dynamics in vivo. A spontaneous mouse mutant, corneal disease
      1(corn1), is deficient for DSTN, which causes epithelial hyperproliferation and
      neovascularization in the cornea. Dstn(corn1) mice exhibit an actin dynamics
      defect in the cornea as evidenced by the formation of actin stress fibers in the
      epithelial cells. Previously, we observed a significant infiltration of
      leukocytes into the cornea of Dstn(corn1) mice as well as the upregulation of
      proinflammatory molecules. In this study, we sought to characterize this
      inflammatory condition and explore the physiological mechanism through which a
      loss of Dstn function leads to inflammation. METHODOLOGY/PRINCIPAL FINDINGS:
      Through immunofluorescent analyses, we observed a significant recruitment of
      neutrophils and macrophages to the Dstn(corn1) cornea, demonstrating that the
      innate immune system is spontaneously activated in this mutant. The inflammatory
      chemokine, CXCL5, was ectopically expressed in the corneal epithelial cells of
      Dstn(corn1) mice, and targeting of the receptor for this chemokine inhibited
      neutrophil recruitment. An inflammatory reaction was not observed in the cornea
      of allelic mutant strain, Dstn(corn1-2J), which has a milder defect in actin
      dynamics in the corneal epithelial cells. CONCLUSIONS/SIGNIFICANCE: This study
      shows that severe defects in actin dynamics lead to an autoinflammatory condition
      that is mediated by the expression of CXC chemokines.

PMID- 18628997
TI  - Tracking the odysseys of juvenile schistosomes to understand host interactions.

PMID- 18628998
TI  - A novel strategy involved in [corrected] anti-oxidative defense: the conversion
      of NADH into NADPH by a metabolic network.
AB  - The reduced nicotinamide adenine dinucleotide phosphate (NADPH) is pivotal to the
      cellular anti-oxidative defence strategies in most organisms. Although its
      production mediated by different enzyme systems has been relatively well-studied,
      metabolic networks dedicated to the biogenesis of NADPH have not been fully
      characterized. In this report, a metabolic pathway that promotes the conversion
      of reduced nicotinamide adenine dinucleotide (NADH), a pro-oxidant into NADPH has
      been uncovered in Pseudomonas fluorescens exposed to oxidative stress. Enzymes
      such as pyruvate carboxylase (PC), malic enzyme (ME), malate dehydrogenase (MDH),
      malate synthase (MS), and isocitrate lyase (ICL) that are involved in disparate
      metabolic modules, converged to create a metabolic network aimed at the
      transformation of NADH into NADPH. The downregulation of phosphoenol
      carboxykinase (PEPCK) and the upregulation of pyruvate kinase (PK) ensured that
      this metabolic cycle fixed NADH into NADPH to combat the oxidative stress
      triggered by the menadione insult. This is the first demonstration of a metabolic
      network invoked to generate NADPH from NADH, a process that may be very effective
      in combating oxidative stress as the increase of an anti-oxidant is coupled to
      the decrease of a pro-oxidant.

PMID- 18628999
TI  - The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy.
AB  - BACKGROUND: In proliferative diabetic retinopathy (PDR), vascular endothelial
      growth factor (VEGF) and connective tissue growth factor (CTGF) cause blindness
      by neovascularization and subsequent fibrosis, but their relative contribution to
      both processes is unknown. We hypothesize that the balance between levels of pro
      angiogenic VEGF and pro-fibrotic CTGF regulates angiogenesis, the angio-fibrotic
      switch, and the resulting fibrosis and scarring. METHODS/PRINCIPAL FINDINGS: VEGF
      and CTGF were measured by ELISA in 68 vitreous samples of patients with
      proliferative DR (PDR, N = 32), macular hole (N = 13) or macular pucker (N = 23)
      and were related to clinical data, including degree of intra-ocular
      neovascularization and fibrosis. In addition, clinical cases of PDR (n = 4) were
      studied before and after pan-retinal photocoagulation and intra-vitreal
      injections with bevacizumab, an antibody against VEGF. Neovascularization and
      fibrosis in various degrees occurred almost exclusively in PDR patients. In PDR
      patients, vitreous CTGF levels were significantly associated with degree of
      fibrosis and with VEGF levels, but not with neovascularization, whereas VEGF
      levels were associated only with neovascularization. The ratio of CTGF and VEGF
      was the strongest predictor of degree of fibrosis. As predicted by these
      findings, patients with PDR demonstrated a temporary increase in intra-ocular
      fibrosis after anti-VEGF treatment or laser treatment. CONCLUSIONS/SIGNIFICANCE:
      CTGF is primarily a pro-fibrotic factor in the eye, and a shift in the balance
      between CTGF and VEGF is associated with the switch from angiogenesis to fibrosis
      in proliferative retinopathy.

PMID- 18629000
TI  - Murine leukemia virus spreading in mice impaired in the biogenesis of secretory
      lysosomes and Ca2+-regulated exocytosis.
AB  - BACKGROUND: Retroviruses have been observed to bud intracellularly into
      multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB
      is thought to occur by Ca(2+)-regulated fusion with the plasma membrane.
      PRINCIPAL FINDINGS: To address the role of the MVB pathway in replication of the
      murine leukemia virus (MLV) we took advantage of mouse models for the Hermansky
      Pudlak syndrome (HPS) and Griscelli syndrome. In humans, these disorders are
      characterized by hypopigmentation and immunological alterations that are caused
      by defects in the biogenesis and trafficking of MVBs and other lysosome related
      organelles. Neonatal mice for these disease models lacking functional AP-3,
      Rab27A and BLOC factors were infected with Moloney MLV and the spread of virus
      into bone marrow, spleen and thymus was monitored. We found a moderate reduction
      in MLV infection levels in most mutant mice, which differed by less than two-fold
      compared to wild-type mice. In vitro, MLV release form bone-marrow derived
      macrophages was slightly enhanced. Finally, we found no evidence for a Ca(2+)
      regulated release pathway in vitro. Furthermore, MLV replication was only
      moderately affected in mice lacking Synaptotagmin VII, a Ca(2+)-sensor regulating
      lysosome fusion with the plasma membrane. CONCLUSIONS: Given that MLV spreading
      in mice depends on multiple rounds of replication even moderate reduction of
      virus release at the cellular level would accumulate and lead to a significant
      effect over time. Thus our in vivo and in vitro data collectively argue against
      an essential role for a MVB- and secretory lysosome-mediated pathway in the
      egress of MLV.

PMID- 18629001
TI  - Activity-dependent shedding of the NMDA receptor glycine binding site by matrix
      metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity.
AB  - Functional and structural alterations of clustered postsynaptic ligand gated ion
      channels in neuronal cells are thought to contribute to synaptic plasticity and
      memory formation in the human brain. Here, we describe a novel molecular
      mechanism for structural alterations of NR1 subunits of the NMDA receptor. In
      cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces
      disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was
      prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed
      the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of
      about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in
      cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by
      immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding
      protein was used to identify MMP-3 cleavage sites within the extracellular S1 and
      S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and
      L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In
      conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in
      the activity dependent alteration of NMDA receptor structure at postsynaptic
      membrane specializations in the CNS.

PMID- 18629002
TI  - Major histocompatibility complex based resistance to a common bacterial pathogen
      of amphibians.
AB  - Given their well-developed systems of innate and adaptive immunity, global
      population declines of amphibians are particularly perplexing. To investigate the
      role of the major histocompatibility complex (MHC) in conferring pathogen
      resistance, we challenged Xenopus laevis tadpoles bearing different combinations
      of four MHC haplotypes (f, g, j, and r) with the bacterial pathogen Aeromonas
      hydrophila in two experiments. In the first, we exposed ff, fg, gg, gj, and jj
      tadpoles, obtained from breeding MHC homozygous parents, to one of three doses of
      A. hydrophila or heat-killed bacteria as a control. In the second, we exposed ff,
      fg, fr, gg, rg, and rr tadpoles, obtained from breeding MHC heterozygous parents
      and subsequently genotyped by PCR, to A. hydrophila, heat-killed bacteria or
      media alone as controls. We thereby determined whether the same patterns of MHC
      resistance emerged within as among families, independent of non-MHC heritable
      differences. Tadpoles with r or g MHC haplotypes were more likely to die than
      were those with f or j haplotypes. Growth rates varied among MHC types,
      independent of exposure dose. Heterozygous individuals with both susceptible and
      resistant haplotypes were intermediate to either homozygous genotype in both size
      and survival. The effect of the MHC on growth and survival was consistent between
      experiments and across families. MHC alleles differentially confer resistance to,
      or tolerance of, the bacterial pathogen, which affects tadpoles' growth and
      survival.

PMID- 18629003
TI  - Rheological characterization of the bundling transition in F-actin solutions
      induced by methylcellulose.
AB  - In many in vitro experiments Brownian motion hampers quantitative data analysis.
      Therefore, additives are widely used to increase the solvent viscosity. For this
      purpose, methylcellulose (MC) has been proven highly effective as already small
      concentrations can significantly slow down diffusive processes. Beside this
      advantage, it has already been reported that high MC concentrations can alter the
      microstructure of polymer solutions such as filamentous actin. However, it
      remains to be shown to what extent the mechanical properties of a composite
      actin/MC gel depend on the MC concentration. In particular, significant
      alterations might occur even if the microstructure seems unaffected. Indeed, we
      find that the viscoelastic response of entangled F-actin solutions depends
      sensitively on the amount of MC added. At concentrations higher than 0.2% (w/v)
      MC, actin filaments are reorganized into bundles which drastically changes the
      viscoelastic response. At small MC concentrations the impact of MC is more
      subtle: the two constituents, actin and MC, contribute in an additive way to the
      mechanical response of the composite material. As a consequence, the effect of
      methylcellulose on actin solutions has to be considered very carefully when MC is
      used in biochemical experiments.

PMID- 18629005
TI  - Quantitative proteomics of lymphocytes.
AB  - Lymphocytes are the best-studied higher eukaryote cells. In this report,
      quantitative relationships of the protein components in resting cell, blast cell
      and plasma cell types are evaluated. The comparison of these cell types leads to
      the conclusion that resting cells synthesize about one-twentieth of the protein
      species as compared to blast cells. Blast cells seem to be metabolically the most
      robust lymphocyte type. Plasma cells are geared towards synthesis of one main
      product (antibody in B plasma cells), while most of the synthesis of other
      protein species (including those for housekeeping and repair) decreases as the
      messages decay. Although the data presented in this communication allow a
      meaningful comparison of three cell populations, they are far from providing a
      full picture. Both silver staining and radiofluorography depict only proteins of
      high or intermediate abundance. Silver staining misses most proteins present at
      <10 000 copies/cell, while radiofluorography misses all those proteins with slow
      turnover (and those with no methionine residue in their sequence). The detection
      of 1100 spots in the blast cell-related radiofluorograph includes visualization
      of some 97-99% of protein mass, but some 3900 polypeptide species in the
      remaining 1-3% of protein mass will pass undetected. This protein mass (0.7-2 pg)
      reflects some 2500-7500 copies of each of those 3900 polypeptide species that are
      present in the cell below the detection limit. The work emphasizes that full
      understanding of cellular function can be achieved only if quantitative aspects
      of cell inventory are considered.

PMID- 18629006
TI  - Post-normalization quality assessment visualization of microarray data.
AB  - Post-normalization checking of microarrays rarely occurs, despite the problems
      that using unreliable data for inference can cause. This paper considers a number
      of different ways to check microarrays after normalization for a variety of
      potential problems. Four types of problem with microarray data that these checks
      can identify are: clerical mistakes, array-wide hybridization problems, problems
      with normalization and mishandling problems. Any of these can seriously affect
      the results of any analysis. The three main techniques used to identify these
      problems are dimension reduction techniques, false array plots and correlograms.
      None of the techniques are computationally very intensive and all can be carried
      out in the R statistical package. Once discovered, problems can either be
      rectified or excluded from the data.

PMID- 18629007
TI  - Fishing with (Proto)Net-a principled approach to protein target selection.
AB  - Structural genomics strives to represent the entire protein space. The first step
      towards achieving this goal is by rationally selecting proteins whose structures
      have not been determined, but that represent an as yet unknown structural
      superfamily or fold. Once such a structure is solved, it can be used as a
      template for modelling homologous proteins. This will aid in unveiling the
      structural diversity of the protein space. Currently, no reliable method for
      accurate 3D structural prediction is available when a sequence or a structure
      homologue is not available. Here we present a systematic methodology for
      selecting target proteins whose structure is likely to adopt a new, as yet
      unknown superfamily or fold. Our method takes advantage of a global
      classification of the sequence space as presented by ProtoNet-3D, which is a
      hierarchical agglomerative clustering of the proteins of interest (the proteins
      in Swiss-Prot) along with all solved structures (taken from the PDB). By
      navigating in the scaffold of ProtoNet-3D, we yield a prioritized list of
      proteins that are not yet structurally solved, along with the probability of each
      of the proteins belonging to a new superfamily or fold. The sorted list has been
      self-validated against real structural data that was not available when the
      predictions were made. The practical application of using our computational
      statistical method to determine novel superfamilies for structural genomics
      projects is also discussed.

PMID- 18629008
TI  - Functional genomics and disease in 2003.

PMID- 18629009
TI  - Genomics in the Czech Republic.

PMID- 18629010
TI  - Analysis of known bacterial protein vaccine antigens reveals biased physical
      properties and amino acid composition.
AB  - Many vaccines have been developed from live attenuated forms of bacterial
      pathogens or from killed bacterial cells. However, an increased awareness of the
      potential for transient side-effects following vaccination has prompted an
      increased emphasis on the use of sub-unit vaccines, rather than those based on
      whole bacterial cells. The identification of vaccine sub-units is often a lengthy
      process and bioinformatics approaches have recently been used to identify
      candidate protein vaccine antigens. Such methods ultimately offer the promise of
      a more rapid advance towards preclinical studies with vaccines. We have compared
      the properties of known bacterial vaccine antigens against randomly selected
      proteins and identified differences in the make-up of these two groups. A
      computer algorithm that exploits these differences allows the identification of
      potential vaccine antigen candidates from pathogenic bacteria on the basis of
      their amino acid composition, a property inherently associated with sub-cellular
      location.

PMID- 18629011
TI  - The Journey to smORFland.
AB  - The genome sequences completed so far contain more than 20 000 genes with unknown
      function and no similarity to genes in other genomes. The origin and evolution of
      the orphan genes is an enigma. Here, we discuss the suggestion that some orphan
      genes may represent pseudogenes or short fragments of genes that were functional
      in the genome of a common ancestor. These may be the remains of unsuccessful
      duplication or horizontal gene transfer events, in which the acquired sequences
      have entered the fragmentation process and thereby lost their similarity to genes
      in other species. This scenario is supported by a recent case study of orphan
      genes in several closely related species of Rickettsia, where full-length
      ancestral genes were reconstructed from sets of short, overlapping orphan genes.
      One of these was found to display similarity to genes encoding proteins with
      ankyrin-repeat domains.

PMID- 18629012
TI  - Padlock and proximity probes for in situ and array-based analyses: tools for the
      post-genomic era.
AB  - Highly specific high-throughput assays will be required to take full advantage of
      the accumulating information about the macromolecular composition of cells and
      tissues, in order to characterize biological systems in health and disease. We
      discuss the general problem of detection specificity and present the approach our
      group has taken, involving the reformatting of analogue biological information to
      digital reporter segments of genetic information via a series of DNA ligation
      assays. The assays enable extensive, coordinated analyses of the numbers and
      locations of genes, transcripts and protein.

PMID- 18629014
TI  - Meeting highlights: genome informatics.
AB  - We bring you the highlights of the second Joint Cold Spring Harbor Laboratory and
      Wellcome Trust 'Genome Informatics' Conference, organized by Ewan Birney, Suzanna
      Lewis and Lincoln Stein. There were sessions on in silico data discovery,
      comparative genomics, annotation pipelines, functional genomics and integrative
      biology. The conference included a keynote address by Sydney Brenner, who was
      awarded the 2002 Nobel Prize in Physiology or Medicine (jointly with John Sulston
      and H. Robert Horvitz) a month later.

PMID- 18629015
TI  - Use of complex DNA and antibody microarrays as tools in functional analyses.
AB  - While the deciphering of basic sequence information on a genomic scale is
      yielding complete genomic sequences in ever-shorter intervals, experimental
      procedures for elucidating the cellular effects and consequences of the DNA
      encoded information become critical for further analyses. In recent years, DNA
      microarray technology has emerged as a prime candidate for the performance of
      many such functional assays. Technically, array technology has come a long way
      since its conception some 15 years ago, initially designed as a means for large
      scale mapping and sequencing.The basic arrangement, however, could be adapted
      readily to serve eventually as an analytical tool in a large variety of
      applications. On their own or in combination with other methods, microarrays open
      up many new avenues of functional analysis.

PMID- 18629016
TI  - ESF Programme on Functional Genomics 1st European Conference: Functional Genomics
      and Disease 2003.
AB  - In this report from the 1st European Conference of the European Science
      Foundation Programme on Functional Genomics, we provide coverage of the high
      profile plenary talks and a cross-section of the many presentations in the
      disease analysis symposia and functional genomics technologies workshops.

PMID- 18629017
TI  - Proteins interacting with Caenorhabditis elegans Galpha subunits.
AB  - To identify novel components in heterotrimeric G-protein signalling, we performed
      an extensive screen for proteins interacting with Caenorhabditis elegans Galpha
      subunits. The genome of C. elegans contains homologues of each of the four
      mammalian classes of Galpha subunits (Gs, Gi/o, Gq and G12), and 17 other Galpha
      subunits. We tested 19 of the GGalpha subunits and four constitutively activated
      Galpha subunits in a largescale yeast two-hybrid experiment. This resulted in the
      identification of 24 clones, representing 11 different proteins that interact
      with four different Galpha subunits. This set includes C. elegans orthologues of
      known interactors of Galpha subunits, such as AGS3 (LGN/PINS), CalNuc and
      Rap1Gap, but also novel proteins, including two members of the nuclear receptor
      super family and a homologue of human haspin (germ cell-specific kinase). All
      interactions were found to be unique for a specific Galpha subunit but variable
      for the activation status of the Galpha subunit. We used expression pattern and
      RNA interference analysis of the G-protein interactors in an attempt to
      substantiate the biological relevance of the observed interactions. Furthermore,
      by means of a membrane recruitment assay, we found evidence that GPA-7 and the
      nuclear receptor NHR-22 can interact in the animal.

PMID- 18629019
TI  - ISMB 2003 Text Mining SIG Meeting Report.

PMID- 18629020
TI  - The characteristics of human genes: analysis of human chromosome 22.

PMID- 18629021
TI  - Gene expression profiling on global cDNA arrays gives hints concerning potential
      signal transduction pathways involved in cardiac fibrosis of renal failure.
AB  - Cardiac remodelling with interstitial fibrosis in renal failure, which so far is
      only poorly understood on the molecular level, was investigated in the rat model
      by a global gene expression profiling analysis. Sprague-Dawley rats were
      subjected to subtotal nephrectomy (SNX) or sham operation (sham) and followed for
      2 and 12 weeks, respectively. Heart-specific gene expression profiling, with RZPD
      Rat Unigene-1 cDNA arrays containing about 27 000 gene and EST sequences revealed
      substantial changes in gene expression in SNX compared to sham animals. Motor
      protein genes, growth and differentiation markers, and extracellular matrix genes
      were upregulated in SNX rats. Obviously, not only genes involved in cardiomyocyte
      hypertrophy, but also genes involved in the expansion of non-vascular
      interstitial tissue are activated very early in animals with renal failure.
      Together with earlier findings in the SNX model, the present data suggest the
      hypothesis that the local renin-angiotensin system (RAS) may be activated by at
      least two pathways: (a) via second messengers and Gproteins (short-term
      signalling); and (b) via motor proteins, actins and integrins (longterm
      signalling). The study documents that complex hybridization analysis yields
      reproducible and promising results of patterns of gene activation pointing to
      signalling pathways involved in cardiac remodelling in renal failure. The
      complete array data are available via http://www.rzpd.de/cgi
      bin/services/exp/viewExpressionData.pl.cgi.

PMID- 18629022
TI  - ISMB 2003 BioPathways SIG and 5th BioPathways Meeting.

PMID- 18629024
TI  - Another Year for CFG.

PMID- 18629023
TI  - Steady-state analysis of genetic regulatory networks modelled by probabilistic
      boolean networks.
AB  - Probabilistic Boolean networks (PBNs) have recently been introduced as a
      promising class of models of genetic regulatory networks. The dynamic behaviour
      of PBNs can be analysed in the context of Markov chains. A key goal is the
      determination of the steady-state (long-run) behaviour of a PBN by analysing the
      corresponding Markov chain. This allows one to compute the long-term influence of
      a gene on another gene or determine the long-term joint probabilistic behaviour
      of a few selected genes. Because matrix-based methods quickly become prohibitive
      for large sizes of networks, we propose the use of Monte Carlo methods. However,
      the rate of convergence to the stationary distribution becomes a central issue.
      We discuss several approaches for determining the number of iterations necessary
      to achieve convergence of the Markov chain corresponding to a PBN. Using a
      recently introduced method based on the theory of two-state Markov chains, we
      illustrate the approach on a sub-network designed from human glioma gene
      expression data and determine the joint steadystate probabilities for several
      groups of genes.

PMID- 18629025
TI  - 11th Intelligent Systems for Molecular Biology 2003 (ISMB 2003).
AB  - This report profiles the keynote talks given at ISMB03 in Brisbane, Australia by
      Ron Shamir, David Haussler, John Mattick, Yoshihide Hayashizaki, Sydney Brenner,
      the Overton Prize winner, Jim Kent, and the ISCB Senior Accomplishment Awardee,
      David Sankov.

PMID- 18629026
TI  - Biobanks for genomics and genomics for biobanks.
AB  - Biobanks include biological samples and attached databases. Human biobanks occur
      in research, technological development and medical activities. Population
      genomics is highly dependent on the availability of large biobanks. Ethical
      issues must be considered: protecting the rights of those people whose samples or
      data are in biobanks (information, autonomy, confidentiality, protection of
      private life), assuring the non-commercial use of human body elements and the
      optimal use of samples and data. They balance other issues, such as protecting
      the rights of researchers and companies, allowing long-term use of biobanks while
      detailed information on future uses is not available. At the level of
      populations, the traditional form of informed consent is challenged. Other
      dimensions relate to the rights of a group as such, in addition to individual
      rights. Conditions of return of results and/or benefit to a population need to be
      defined. With 'large-scale biobanking' a marked trend in genomics, new societal
      dimensions appear, regarding communication, debate, regulation, societal control
      and valorization of such large biobanks. Exploring how genomics can help health
      sector biobanks to become more rationally constituted and exploited is an
      interesting perspective. For example, evaluating how genomic approaches can help
      in optimizing haematopoietic stem cell donor registries using new markers and
      high-throughput techniques to increase immunogenetic variability in such
      registries is a challenge currently being addressed. Ethical issues in such
      contexts are important, as not only individual decisions or projects are
      concerned, but also national policies in the international arena and organization
      of democratic debate about science, medicine and society.

PMID- 18629027
TI  - Structure and sequence of the human fast skeletal troponin T (TNNT3) gene:
      insight into the evolution of the gene and the origin of the developmentally
      regulated isoforms.
AB  - We describe the cloning, sequencing and structure of the human fast skeletal
      troponin T (TNNT3) gene located on chromosome 11p15.5. The single-copy gene
      encodes 19 exons and 18 introns. Eleven of these exons, 1-3, 9-15 and 18, are
      constitutively spliced, whereas exons 4-8 are alternatively spliced. The gene
      contains an additional subset of developmentally regulated and alternatively
      spliced exons, including a foetal exon located between exon 8 and 9 and exon 16
      or alpha (adult) and 17 or beta (foetal and neonatal). Exon phasing suggests that
      the majority of the alternatively spliced exons located at the 5' end of the gene
      may have evolved as a result of exon shuffling, because they are of the same
      phase class. In contrast, the 3' exons encoding an evolutionarily conserved
      heptad repeat domain, shared by both TnT and troponin I (TnI), may be remnants of
      an ancient ancestral gene. The sequence of the 5' flanking region shows that the
      putative promoter contains motifs including binding sites for MyoD, MEF-2 and
      several transcription factors which may play a role in transcriptional regulation
      and tissue-specific expression of TnT. The coding region of TNNT3 exhibits strong
      similarity to the corresponding rat sequence. However, unlike the rat TnT gene,
      TNNT3 possesses two repeat regions of CCA and TC. The exclusive presence of these
      repetitive elements in the human gene indicates divergence in the evolutionary
      dynamics of mammalian TnT genes. Homologous muscle-specific splicing enhancer
      motifs are present in the introns upstream and downstream of the foetal exon, and
      may play a role in the developmental pattern of alternative splicing of the gene.
      The genomic correlates of TNNT3 are relevant to our understanding of the
      evolution and regulation of expression of the gene, as well as the structure and
      function of the protein isoforms. The nucleotide sequence of TNNT3 has been
      submitted to EMBL/GenBank under Accession No. AF026276.

PMID- 18629028
TI  - ISMB 2003 Bio-ontologies SIG and Sixth Annual Bio-ontologies Meeting Report.
AB  - The Annual Bio-Ontologies meeting (http://www.cs.man.ac.uk/ stevens/meeting03/)
      has now been running for 6 consecutive years, as a special interest group (SIG)
      of the much larger ISMB conference. It met in Brisbane, Australia, this summer,
      the first time it was held outside North America or Europe. The bio-ontologies
      meeting is 1 day long and normally has around 100 attendees. This year there were
      many fewer, no doubt a result of the distance, global politics and SARS. The
      meeting consisted of a series of 30 min talks with no formal peer review or
      publication. Talks ranged in style from fairly formal and complete pieces of
      work, through works in progress, to the very informal and discursive. Each year's
      meeting has a theme and this year it was 'ontologies, and text processing'. There
      is a tendency for those submitting talks to ignore the theme completely, but this
      year's theme obviously struck a chord, as half the programme was about ontologies
      and text analysis (http://www.cs.man.ac.uk/ stevensr/meeting03/programme.html).
      Despite the smaller size of the meeting, the programme was particularly strong
      this year, meaning that the tension between allowing time for the many excellent
      talks, discussion and questions from the floor was particular keenly felt. A
      happy problem to have!

PMID- 18629030
TI  - A molecular phylogenomic analysis of the ILR1-like family of IAA amidohydrolase
      genes.
AB  - The ILR1-like family of hydrolase genes was initially isolated in Arabidopsis
      thaliana and is thought to help regulate levels of free indole-3-acetic-acid.We
      have investigated how this family has evolved in dicotyledon, monocotyledon and
      gymnosperm species by employing the GenBank and TIGR databases to retrieve
      orthologous genes. The relationships among these sequences were assessed
      employing phylogenomic analyses to examine molecular evolution and phylogeny. The
      members of the ILR1-like family analysed were ILL1, ILL2, ILL3, ILL6, ILR1 and
      IAR3. Present evidence suggests that IAR3 has undergone the least evolution and
      is most conserved. This conclusion is based on IAR3 having the largest number of
      total interspecific orthologues, orthologous species and unique orthologues.
      Although less conserved than IAR3, DNA and protein sequence analyses of ILL1 and
      ILR1 suggest high conservation. Based on this conservation, IAR3, ILL1 and ILR1
      may have had major roles in the physiological evolution of 'higher' plants. ILL3
      is least conserved, with the fewest orthologous species and orthologues. The
      monocotyledonous orthologues for most family-members examined have evolved into
      two separate molecular clades from dicotyledons, indicating active evolutionary
      change. The monocotyledon clades are: (a) those possessing a putative endoplasmic
      reticulum localizing signal; and (b) those that are putative cytoplasmic
      hydrolases. IAR3, ILL1 and ILL6 are all highly orthologous to a gene in the
      gymnosperm Pinus taeda, indicating an ancient enzymatic activity. No orthologues
      could be detected in Chlamydomonas, moss and fern databases.

PMID- 18629031
TI  - Critical assessment of information extraction systems in biology.
AB  - An increasing number of groups are now working in the area of text mining,
      focusing on a wide range of problems and applying both statistical and linguistic
      approaches. However, it is not possible to compare the different approaches,
      because there are no common standards or evaluation criteria; in addition, the
      various groups are addressing different problems, often using private datasets.
      As a result, it is impossible to determine how well the existing systems perform,
      and particularly what performance level can be expected in real applications.
      This is similar to the situation in text processing in the late 1980s, prior to
      the Message Understanding Conferences (MUCs). With the introduction of a common
      evaluation and standardized evaluation metrics as part of these conferences, it
      became possible to compare approaches, to identify those techniques that did or
      did not work and to make progress. This progress has resulted in a common
      pipeline of processes and a set of shared tools available to the general research
      community. The field of biology is ripe for a similar experiment. Inspired by
      this example, the BioLINK group (Biological Literature, Information and Knowledge
      [1]) is organizing a CASP-like evaluation for the text data-mining community
      applied to biology. The two main tasks specifically address two major bottlenecks
      for text mining in biology: (1) the correct detection of gene and protein names
      in text; and (2) the extraction of functional information related to proteins
      based on the GO classification system. For further information and participation
      details, see http://www.pdg.cnb.uam.es/BioLink/BioCreative.eval.html.

PMID- 18629032
TI  - Segmental trisomy of mouse chromosome 17: introducing an alternative model of
      Down's syndrome.
AB  - All of the mouse models of human trisomy 21 syndrome that have been studied so
      far are based on segmental trisomies, encompassing, to a varying extent, distal
      chromosome 16. Their comparison with one or more unrelated and non-overlapping
      segmental trisomies may help to distinguish the effects of specific triplicated
      genes from the phenotypes caused by less specific developmental instability
      mechanisms. In this paper, the Ts43H segmental trisomy of mouse chromosome 17 is
      presented as such an alternative model. The trisomy stretches over 32.5 Mb of
      proximal chromosome 17 and includes 486 genes. The triplicated interval carries
      seven blocks of synteny with five human chromosomes. The block syntenic to human
      chromosome 21 contains 20 genes.

PMID- 18629033
TI  - Computational aspects of protein functionality.
AB  - The purpose of this short article is to examine certain aspects of protein
      functionality with relation to some key organizing ideas. This is important from
      a computational viewpoint in order to take account of modelling both biological
      systems and knowledge of these systems. We look at some of the lexical dimensions
      of the function and how certain constructs can be related to underlying ideas.
      The pervasive computational metaphor is then discussed in relation to protein
      multifunctionality, and the specific case of von Willebrand factor as a 'smart'
      multifunctional protein is briefly considered. Some diagrammatic techniques are
      then introduced to better articulate protein function.

PMID- 18629034
TI  - The evolution of protein interaction networks in regulatory proteins.
AB  - Interactions between proteins are essential for intracellular communication. They
      form complex networks which have become an important source for functional
      analysis of proteins. Combining phylogenies with network analysis, we investigate
      the evolutionary history of interaction networks from the bHLH, NR and bZIP
      transcription-factor families. The bHLH and NR networks show a hub-like structure
      with varying gamma values. Mutation and gene duplication play an important role
      in adding and removing interactions. We conclude that in several of the protein
      families that we have studied, networks have primarily arisen by the development
      of heterodimerizing transcription factors, from an ancestral gene which interacts
      with any of the newly emerging proteins but also homodimerizes.

PMID- 18629035
TI  - UTOPIA-User-Friendly Tools for Operating Informatics Applications.
AB  - Bioinformaticians routinely analyse vast amounts of information held both in
      large remote databases and in flat data files hosted on local machines. The
      contemporary toolkit available for this purpose consists of an ad hoc collection
      of data manipulation tools, scripting languages and visualization systems; these
      must often be combined in complex and bespoke ways, the result frequently being
      an unwieldy artefact capable of one specific task, which cannot easily be
      exploited or extended by other practitioners. Owing to the sizes of current
      databases and the scale of the analyses necessary, routine bioinformatics tasks
      are often automated, but many still require the unique experience and intuition
      of human researchers: this requires tools that support real-time interaction with
      complex datasets. Many existing tools have poor user interfaces and limited real
      time performance when applied to realistically large datasets; much of the user's
      cognitive capacity is therefore focused on controlling the tool rather than on
      performing the research. The UTOPIA project is addressing some of these issues by
      building reusable software components that can be combined to make useful
      applications in the field of bioinformatics. Expertise in the fields of human
      computer interaction, high-performance rendering, and distributed systems is
      being guided by bioinformaticians and end-user biologists to create a toolkit
      that is both architecturally sound from a computing point of view, and directly
      addresses end-user and application-developer requirements.

PMID- 18629036
TI  - ArraySolver: an algorithm for colour-coded graphical display and Wilcoxon signed
      rank statistics for comparing microarray gene expression data.
AB  - The massive surge in the production of microarray data poses a great challenge
      for proper analysis and interpretation. In recent years numerous computational
      tools have been developed to extract meaningful interpretation of microarray gene
      expression data. However, a convenient tool for two-groups comparison of
      microarray data is still lacking and users have to rely on commercial statistical
      packages that might be costly and require special skills, in addition to extra
      time and effort for transferring data from one platform to other. Various
      statistical methods, including the t-test, analysis of variance, Pearson test and
      Mann-Whitney U test, have been reported for comparing microarray data, whereas
      the utilization of the Wilcoxon signed-rank test, which is an appropriate test
      for two-groups comparison of gene expression data, has largely been neglected in
      microarray studies. The aim of this investigation was to build an integrated
      tool, ArraySolver, for colour-coded graphical display and comparison of gene
      expression data using the Wilcoxon signed-rank test. The results of software
      validation showed similar outputs with ArraySolver and SPSS for large datasets.
      Whereas the former program appeared to be more accurate for 25 or fewer pairs (n
      < or = 25), suggesting its potential application in analysing molecular
      signatures that usually contain small numbers of genes. The main advantages of
      ArraySolver are easy data selection, convenient report format, accurate
      statistics and the familiar Excel platform.

PMID- 18629037
TI  - A formal language-based approach in biology.
AB  - This paper presents an overview of computational biology approaches and surveys
      some of the natural computing models using, in both cases, a formal language
      based approach.

PMID- 18629038
TI  - ProbSeq--a fragmentation model for interpretation of electrospray tandem mass
      spectrometry data.
AB  - We describe a probabilistic peptide fragmentation model for use in protein
      databank searching and de novo sequencing of electrospray tandem mass
      spectrometry data. A probabilistic framework for tuning of the model using a
      range of well-characterized samples are introduced. We present preliminary
      results of our tuning efforts.

PMID- 18629039
TI  - Enabling proteomics: the need for an extendable 'workbench' for user-configurable
      solutions.
AB  - Proteomics has the capability to generate overwhelming quantities of data in
      relatively short timescales, and it is not uncommon to see experimenters
      investing substantially more time in data analysis than in data gathering.
      Although several sophisticated tools for data reduction and analysis are
      available, they lack the flexibility to cope with increasingly innovative
      experimental strategies and new database resources that encode both qualitative
      and quantitative data. I will outline a specification of a flexible proteomics
      tool that could address many current bottlenecks and deficiencies.

PMID- 18629041
TI  - Individual-based modelling of bacterial ecologies and evolution.
AB  - This paper presents two approaches to the individual-based modelling of bacterial
      ecologies and evolution using computational tools. The first approach is a fine
      grained model that is based on networks of interactivity between computational
      objects representing genes and proteins. The second approach is a coarser
      grained, agent-based model, which is designed to explore the evolvability of
      adaptive behavioural strategies in artificial bacteria represented by learning
      classifier systems. The structure and implementation of these computational
      models is discussed, and some results from simulation experiments are presented.
      Finally, the potential applications of the proposed models to the solution of
      real-world computational problems, and their use in improving our understanding
      of the mechanisms of evolution, are briefly outlined.

PMID- 18629042
TI  - Identification and analysis of novel tandem repeats in the cell surface proteins
      of archaeal and bacterial genomes using computational tools.
AB  - We have identified four novel repeats and two domains in cell surface proteins
      encoded by the Methanosarcina acetivorans genome and in some archaeal and
      bacterial genomes. The repeats correspond to a certain number of amino acid
      residues present in tandem in a protein sequence and each repeat is characterized
      by conserved sequence motifs. These correspond to: (a) a 42 amino acid (aa)
      residue RIVW repeat; (b) a 45 aa residue LGxL repeat; (c) a 42 aa residue LVIVD
      repeat; and (d) a 54 aa residue LGFP repeat. The domains correspond to a certain
      number of aa residues in a protein sequence that do not comprise internal
      repeats. These correspond to: (a) a 200 aa residue DNRLRE domain; and (b) a 70 aa
      residue PEGA domain. We discuss the occurrence of these repeats and domains in
      the different proteins and genomes analysed in this work.

PMID- 18629043
TI  - Rewriting systems and the modelling of biological systems.
AB  - This paper gives a brief survey of the use of algebraic rewriting systems for
      modelling and simulating various biological processes, particularly at the
      cellular level.

PMID- 18629045
TI  - Modelling for integration with proteins, networks and signals.

PMID- 18629044
TI  - A survey of nucleotide cyclases in actinobacteria: unique domain organization and
      expansion of the class III cyclase family in Mycobacterium tuberculosis.
AB  - Cyclic nucleotides are well-known second messengers involved in the regulation of
      important metabolic pathways or virulence factors. There are six different
      classes of nucleotide cyclases that can accomplish the task of generating cAMP,
      and four of these are restricted to the prokaryotes. The role of cAMP has been
      implicated in the virulence and regulation of secondary metabolites in the phylum
      Actinobacteria, which contains important pathogens, such as Mycobacterium
      tuberculosis, M. leprae, M. bovis and Corynebacterium, and industrial organisms
      from the genus Streptomyces. We have analysed the actinobacterial genome
      sequences found in current databases for the presence of different classes of
      nucleotide cyclases, and find that only class III cyclases are present in these
      organisms. Importantly, prominent members such as M. tuberculosis and M. leprae
      have 17 and 4 class III cyclases, respectively, encoded in their genomes, some of
      which display interesting domain fusions seen for the first time. In addition, a
      pseudogene corresponding to a cyclase from M. avium has been identified as the
      only cyclase pseudogene in M. tuberculosis and M. bovis. The Corynebacterium and
      Streptomyces genomes encode only a single adenylyl cyclase each, both of which
      have corresponding orthologues in M. tuberculosis. A clustering of the cyclase
      domains in Actinobacteria reveals the presence of typical eukaryote-like, fungi
      like and other bacteria-like class III cyclase sequences within this phylum,
      suggesting that these proteins may have significant roles to play in this
      important group of organisms.

PMID- 18629046
TI  - MicroCore: mapping genome expression to cell pathways and networks.
AB  - The MicroCore toolkit is a suite of analysis programs for microarray and
      proteomics data that is open source and programmed exclusively in Java. MicroCore
      provides a flexible and extensible environment for the interpretation of
      functional genomics data through visualization. The first version of the
      application (downloadable from the MicroCore website:
      http://www.ucl.ac.uk/oncology/MicroCore/microcore.htm), implements two programs
      PIMs (protein interaction maps) and MicroExpress-and is soon to be followed by an
      extended version which will also feature a fuzzy k-means clustering application
      and a Java-based R plug-in for microarray analysis. PIMs and MicroExpress provide
      a simple yet powerful way of graphically relating large quantities of expression
      data from multiple experiments to cellular pathways and biological processes in a
      statistically meaningful way.

PMID- 18629047
TI  - Signal analysis on strings for immune-type pattern recognition.
AB  - We use wavelet-type discrete transforms for signal analysis on strings of finite
      length. We apply these transforms for edge and hidden Markov process detection.
      We also present new approaches for string matching and for measures of the
      diversity of chaotic strings.

PMID- 18629048
TI  - The 50th ASMS Conference on Mass Spectrometry and Allied Topics.
AB  - Development of new mass spectrometers and implementation of new analytical
      methods were the central themes of the conference. The majority of oral
      presentations and posters were concerned with the application of mass
      spectrometry to pharmaceutical and biotechnological research.

PMID- 18629049
TI  - Upstream - news in genomics.
AB  - This report on the literature spans from May to July, highlighting breakthroughs
      on several important genomes, including mouse, zebrafish, Fugu and Plasmodium.
      Recent papers have reported on a mechanism for genome size reduction in
      Arabidopsis, comparisons and verifications of large-scale protein-protein
      interaction datasets, developments in RNA interference approaches for mammalian
      systems and a solidphase peptide tagging method for proteomics.

PMID- 18629052
TI  - A mathematical model for suppression subtractive hybridization.
AB  - Suppression subtractive hybridization (SSH) is frequently used to unearth
      differentially expressed genes on a whole-genome scale. Its versatility is based
      on combining cDNA library subtraction and normalization, which allows the
      isolation of sequences of varying degrees of abundance and differential
      expression. SSH is a complex process with many adjustable parameters that affect
      the outcome of gene isolation.We present a mathematical model of SSH based on DNA
      hybridization kinetics for assessing the effect of various parameters to
      facilitate its optimization. We derive an equation for the probability that a
      particular differentially expressed species is successfully isolated and use this
      to quantify the effect of the following parameters related to the cDNA sample:
      (a) mRNA abundance; (b) partial sequence complementarity to other species; and
      (3) degree of differential expression. We also evaluate the effect of parameters
      related to the process, including: (a) reaction times; and (b) extent of driver
      excess used in the two hybridization reactions. The optimum set of process
      parameters for successful isolation of differentially expressed species depends
      on transcript abundance. We show that the reaction conditions have a significant
      effect on the occurrence of false-positives and formulate strategies to isolate
      specific subsets of differentially expressed genes. We also quantify the effect
      of non-specific hybridization on the false-positive results and present
      strategies for spiking cDNA sequences to address this problem.

PMID- 18629054
TI  - From genotype to phenotype: linking bioinformatics and medical informatics
      ontologies.
AB  - A small group of around 40 people came together at the Chancellors Conference
      Centre in Manchester for the Ontologies Workshop, chaired by Alan Rector and
      Robert Stevens. The workshop was, rather strangely, spread over 2 half days. In
      hindsight, this programme worked very well as it gave people the opportunity to
      chat over a drink on the Saturday evening and share ideas, before launching into
      the second half on the following day. The participants were from various walks of
      life, all with a common interest in finding out more about ontologies and
      promoting collaborations between the medical informatics and bioinformatics
      ontology communities.

PMID- 18629053
TI  - Meeting Review: ESF workshop on 'Impact of nucleic acid chemistry on gene
      function analysis: antisense, aptamers, ribozymes and RNAi'.

PMID- 18629055
TI  - A computational strategy for protein function assignment which addresses the
      multidomain problem.
AB  - A method for assigning functions to unknown sequences based on finding
      correlations between short signals and functional annotations in a protein
      database is presented. This approach is based on keyword (KW) and feature (FT)
      information stored in the SWISS-PROT database. The former refers to particular
      protein characteristics and the latter locates these characteristics at a
      specific sequence position. In this way, a certain keyword is only assigned to a
      sequence if sequence similarity is found in the position described by the FT
      field. Exhaustive tests performed over sequences with homologues (cluster set)
      and without homologues (singleton set) in the database show that assigning
      functions is much 'cleaner' when information about domains (FT field) is used,
      than when only the keywords are used.

PMID- 18629056
TI  - CCP11 group meeting - towards the functional analysis of microarrays.
AB  - The CCP11 project aims to foster bioinformatics in the UK through conferences,
      workshops and the provision of Web resources. In March 2002, CCP11 held a meeting
      in Manchester, UK, on the functional analysis of microarrays. This was part of
      Manchester BioinformaticsWeek-three consecutive short bioinformatics meetings
      held in the attractive setting of the Chancellor's Conference Centre at the
      University of Manchester. The other meetings in the series were a workshop on
      ontologies and the 12th Annual MASAMB (Mathematical and Statistical Aspects of
      Molecular Biology) Conference. Many delegates were able to attend more than one
      meeting, which led to a useful cross-fertilization of ideas across the
      bioinformatics community. The CCP11 meeting shared with MASAMB a strong emphasis
      on the statistical analysis and interpretation of data-most often image intensity
      data.

PMID- 18629057
TI  - Interoperability of CABRI Services and Biochemical Pathways Databases.
AB  - Common Access to Biological Resources and Information (CABRI) service is a 'one
      stop-shop' for materials that are collected by a number of European culture
      collections that engage themselves in a quality service for the scientific
      community by adhering to Quality Guidelines for the management of resources and
      related information. It includes collections' catalogues that can be searched in
      an SRS implementation. A simple search facility, including a synonym search and a
      shopping cart, is also available. Within the European Biological Resource Centres
      Network (EBRCN) project, an extension and improvement of the catalogues'
      information is under way. This includes adding links to bibliographic databanks
      and sequence databases. Revision of 'in-house' controlled vocabularies used by
      data annotators is under way, in order to improve the setting up of external
      links, and new links to biochemical pathways databases are being set up for some
      of the catalogues.

PMID- 18629059
TI  - The PlaNet Consortium: a network of European plant databases connecting plant
      genome data in an integrated biological knowledge resource.
AB  - The completion of the Arabidopsis genome and the large collections of other plant
      sequences generated in recent years have sparked extensive functional genomics
      efforts. However, the utilization of this data is inefficient, as data sources
      are distributed and heterogeneous and efforts at data integration are lagging
      behind. PlaNet aims to overcome the limitations of individual efforts as well as
      the limitations of heterogeneous, independent data collections. PlaNet is a
      distributed effort among European bioinformatics groups and plant molecular
      biologists to establish a comprehensive integrated database in a collaborative
      network. Objectives are the implementation of infrastructure and data sources to
      capture plant genomic information into a comprehensive, integrated platform. This
      will facilitate the systematic exploration of Arabidopsis and other plants. New
      methods for data exchange, database integration and access are being developed to
      create a highly integrated, federated data resource for research. The connection
      between the individual resources is realized with BioMOBY. BioMOBY provides an
      architecture for the discovery and distribution of biological data through web
      services. While knowledge is centralized, data is maintained at its primary
      source without a need for warehousing. To standardize nomenclature and data
      representation, ontologies and generic data models are defined in interaction
      with the relevant communities.Minimal data models should make it simple to allow
      broad integration, while inheritance allows detail and depth to be added to more
      complex data objects without losing integration. To allow expert annotation and
      keep databases curated, local and remote annotation interfaces are provided. Easy
      and direct access to all data is key to the project.

PMID- 18629060
TI  - Three novel pigmentation mutants generated by genome-wide random ENU mutagenesis
      in the mouse.
AB  - Three mutant mice with pigmentation phenotypes were recovered from a genomewide
      random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly
      spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991)
      were identified following visual inspection of progeny from a male exposed to the
      point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative
      mutations, genome-wide linkage scans were performed on pooled DNA samples from
      backcross animals for each mutant line. Whto was mapped to proximal mouse
      chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the
      centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and
      D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18
      (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the
      elucidation of genetic and biochemical pathways relevant to pigmentation and
      associated biological processes.

PMID- 18629061
TI  - Phylogenetics in the bioinformatics culture of understanding.
AB  - Bioinformatics, as a relatively young discipline, has grown up in a world of high
      throughput large volume data that requires automatic analysis to enable us to
      stay on top of it all. As a response, the bioinformatics discipline has developed
      strategies to find patterns in a 'low signal : noise ratio' environment. While
      the need to process large amounts of information and extract hypotheses is both
      laudable and inescapable, the pressures that such requirements have introduced
      can lead to short cuts and misapprehensions. This is particularly the case with
      reference to assumptions about the underlying evolutionary theories that are
      implicitly invoked by the algorithms utilised in the analysis pipelines. The
      classic example is the misuse of the term 'homologous' to mean 'similar' or even
      'functionally similar', rather than the correct definition of 'having the same
      evolutionary origin', which may or may not imply similarity of function. In this
      review, we outline some of the common phylogenetic questions from a
      bioinformatics perspective that can be better addressed with a deeper
      understanding of evolutionary principles and show, with examples from the
      amidohydrolase and Toll families, that quite different conclusions can be drawn
      if such approaches are taken. This review focuses on the importance of the
      underlying evolutionary biology, rather than assessing the merits of different
      phylogenetic techniques. The relative merits of a priori and a posteriori
      inclusion of biological information are discussed.

PMID- 18629062
TI  - Interactome data and databases: different types of protein interaction.
AB  - In recent years, the biomolecular sciences have been driven forward by
      overwhelming advances in new biotechnological high-throughput experimental
      methods and bioinformatic genome-wide computational methods. Such breakthroughs
      are producing huge amounts of new data that need to be carefully analysed to
      obtain correct and useful scientific knowledge. One of the fields where this
      advance has become more intense is the study of the network of 'protein-protein
      interactions', i.e. the 'interactome'. In this short review we comment on the
      main data and databases produced in this field in last 5 years. We also present a
      rationalized scheme of biological definitions that will be useful for a better
      understanding and interpretation of 'what a protein-protein interaction is' and
      'which types of protein-protein interactions are found in a living cell'.
      Finally, we comment on some assignments of interactome data to defined types of
      protein interaction and we present a new bioinformatic tool called APIN (Agile
      Protein Interaction Network browser), which is in development and will be applied
      to browsing protein interaction databases.

PMID- 18629064
TI  - TRANSPATH--a high quality database focused on signal transduction.
AB  - TRANSPATH can either be used as an encyclopedia, for both specific and general
      information on signal transduction, or can serve as a network analyser.
      Therefore, three modules have been created: the first one is the data, which have
      been manually extracted, mostly from the primary literature; the second is
      PathwayBuilder, which provides several different types of network visualization
      and hence faciliates understanding; the third is ArrayAnalyzer, which is
      particularly suited to gene expression array interpretation, and is able to
      identify key molecules within signalling networks (potential drug targets). These
      key molecules could be responsible for the coordinated regulation of downstream
      events. Manual data extraction focuses on direct reactions between signalling
      molecules and the experimental evidence for them, including species of
      genes/proteins used in individual experiments, experimental systems, materials
      and methods. This combination of materials and methods is used in TRANSPATH to
      assign a quality value to each experimentally proven reaction, which reflects the
      probability that this reaction would happen under physiological conditions.
      Another important feature in TRANSPATH is the inclusion of transcription factor
      gene relations, which are transferred from TRANSFAC, a database focused on
      transcription regulation and transcription factors. Since interactions between
      molecules are mainly direct, this allows a complete and stepwise pathway
      reconstruction from ligands to regulated genes. More information is available at
      www.biobase.de/pages/products/databases.html.

PMID- 18629065
TI  - Looking for cancer clues in publicly accessible databases.
AB  - What started out as a mere attempt to tentatively identify proteins in
      experimental cancer-related 2D-PAGE maps developed into VIRTUAL2D, a web
      accessible repository for theoretical pI/MW charts for 92 organisms. Using
      publicly available expression data, we developed a collection of tissue-specific
      plots based on differential gene expression between normal and diseased states.
      We use this comparative cancer proteomics knowledge base, known as the tissue
      molecular anatomy project (TMAP), to uncover threads of cancer markers common to
      several types of cancer and to relate this information to established biological
      pathways.

PMID- 18629066
TI  - Classification of chemical compounds to support complex queries in a pathway
      database.
AB  - Data quality in biological databases has become a topic of great discussion. To
      provide high quality data and to deal with the vast amount of biochemical data,
      annotators and curators need to be supported by software that carries out part of
      their work in an (semi-) automatic manner. The detection of errors and
      inconsistencies is a part that requires the knowledge of domain experts, thus in
      most cases it is done manually, making it very expensive and time-consuming. This
      paper presents two tools to partially support the curation of data on biochemical
      pathways. The tool enables the automatic classification of chemical compounds
      based on their respective SMILES strings. Such classification allows the querying
      and visualization of biochemical reactions at different levels of abstraction,
      according to the level of detail at which the reaction participants are
      described. Chemical compounds can be classified in a flexible manner based on
      different criteria. The support of the process of data curation is provided by
      facilitating the detection of compounds that are identified as different but that
      are actually the same. This is also used to identify similar reactions and, in
      turn, pathways.

PMID- 18629067
TI  - The ESF Programme on Functional Genomics Workshop on 'Data Integration in
      Functional Genomics: Application to Biological Pathways'.
AB  - We report from the second ESF Programme on Functional Genomics workshop on Data
      Integration, which covered topics including the status of biological pathways
      databases in existing consortia; pathways as part of bioinformatics
      infrastructures; design, creation and formalization of biological pathways
      databases; generating and supporting pathway data and interoperability of
      databases with other external databases and standards. Key issues emerging from
      the discussions were the need for continued funding to cover maintenance and
      curation of databases, the importance of quality control of the data in these
      resources, and efforts to facilitate the exchange of data and to ensure the
      interoperability of databases.

PMID- 18629069
TI  - A Special Section of Articles From the ESF Programme on Functional Genomics
      Workshop: 'Data Integration in Functional Genomics and Proteomics: Application to
      Biological Pathways'.

PMID- 18629068
TI  - Data integration and analysis for medical systems biology.

PMID- 18629070
TI  - From databases to modelling of functional pathways.
AB  - This short review comments on current informatics resources and methodologies in
      the study of functional pathways in cell biology. It highlights recent
      achievements in unveiling the structural design of protein and gene networks and
      discusses current approaches to model and simulate the dynamics of regulatory
      pathways in the cell.

PMID- 18629072
TI  - A fragment of 21 ORFs around the direct repeat (DR) region of Mycobacterium
      tuberculosis is absent from the other sequenced mycobacterial genomes:
      implications for the evolution of the DR region.
AB  - The direct repeat (DR) region is a singular locus of the Mycobacterium
      tuberculosis complex genome. This region consists of 36 bp repetitive sequences
      separated by non-repetitive unique spacer sequences. Around this region there are
      several genes coding for proteins of unknown function. To determine whether the
      M. smegmatis, M. avium, M. marinum and M. leprae genomes contain sequences and
      ORFs similar to those of the DR locus of the M. tuberculosis complex, we analysed
      the corresponding regions in these species. As a first step, some conserved genes
      that flank the DR genes [Rv2785c (rpsO), Rv2786c (ribF), Rv2790c (ltp1 ), Rv2793c
      (truB), Rv2800, Rv2825, Rv2828, Rv2831 (echA16 ), Rv2838 (rbfA) and Rv2845 (proS
      )] were used as markers to locate the corresponding orthologues in M. smegmatis,
      M. avium, M. marinum and M. leprae in silico. Most of these M. tuberculosis
      marker genes have highly similar orthologues located in the same order and
      orientation in the other mycobacteria. In contrast, no orthologues were found for
      ORFs Rv2801-Rv2824, suggesting that these genes are unique to M. tuberculosis
      within the genus Mycobacterium.We observed that in M. smegmatis and M. avium,
      Rv2800 and Rv2825 are adjacent. This observation was experimentally confirmed by
      PCR. In conclusion, as the DR locus and the ORFs around it are absent in M.
      smegmatis and M. avium and, as it is possible that these species are older than
      M. tuberculosis, we postulated that the DR locus was acquired by the M.
      tuberculosis complex species or by an ancestor bacterium.

PMID- 18629073
TI  - Shaping biological knowledge: applications in proteomics.
AB  - The central dogma of molecular biology has provided a meaningful principle for
      data integration in the field of genomics. In this context, integration reflects
      the known transitions from a chromosome to a protein sequence: transcription,
      intron splicing, exon assembly and translation. There is no such clear principle
      for integrating proteomics data, since the laws governing protein folding and
      interactivity are not quite understood. In our effort to bring together
      independent pieces of information relative to proteins in a biologically
      meaningful way, we assess the bias of bioinformatics resources and consequent
      approximations in the framework of small-scale studies. We analyse proteomics
      data while following both a data-driven (focus on proteins smaller than 10 kDa)
      and a hypothesis-driven (focus on whole bacterial proteomes) approach. These
      applications are potentially the source of specialized complements to classical
      biological ontologies.

PMID- 18629074
TI  - Genome-wide analysis of the yeast transcriptome upon heat and cold shock.
AB  - DNA arrays were used to measure changes in transcript levels as yeast cells
      responded to temperature shocks. The number of genes upregulated by temperature
      shifts from 30 to 37 or 45 was correlated with the severity of the stress. Pre
      adaptation of cells, by growth at 37 previous to the 45 shift, caused a decrease
      in the number of genes related to this response. Heat shock also caused
      downregulation of a set of genes related to metabolism, cell growth and division,
      transcription, ribosomal proteins, protein synthesis and destination. Probably
      all of these responses combine to slow down cell growth and division during heat
      shock, thus saving energy for cell rescue. The presence of putative binding sites
      for Xbp1p in the promoters of these genes suggests a hypothetical role for this
      transcriptional repressor, although other mechanisms may be considered. The
      response to cold shock (4) affected a small number of genes, but the vast
      majority of those genes induced by exposure to 4 were also induced during heat
      shock; these genes share in their promoters cis-regulatory elements previously
      related to other stress responses.

PMID- 18629075
TI  - Protein-DNA interactions: the story so far and a new method for prediction.
AB  - This review describes methods for the prediction of DNA binding function, and
      specifically summarizes a new method using 3D structural templates. The new
      method features the HTH motif that is found in approximately one-third of
      DNAbinding protein families. A library of 3D structural templates of HTH motifs
      was derived from proteins in the PDB. Templates were scanned against complete
      protein structures and the optimal superposition of a template on a structure
      calculated. Significance thresholds in terms of a minimum root mean squared
      deviation (rmsd) of an optimal superposition, and a minimum motif accessible
      surface area (ASA), have been calculated. In this way, it is possible to scan the
      template library against proteins of unknown function to make predictions about
      DNA-binding functionality.

PMID- 18629076
TI  - Unravelling the ORFan Puzzle.
AB  - ORFans are open reading frames (ORFs) with no detectable sequence similarity to
      any other sequence in the databases. Each newly sequenced genome contains a
      significant number of ORFans. Therefore, ORFans entail interesting evolutionary
      puzzles. However, little can be learned about them using bioinformatics tools,
      and their study seems to have been underemphasized. Here we present some of the
      questions that the existence of so many ORFans have raised and review some of the
      studies aimed at understanding ORFans, their functions and their origins. These
      works have demonstrated that ORFans are an untapped source of research, requiring
      further computational and experimental studies.

PMID- 18629077
TI  - Multiple sequence alignments as tools for protein structure and function
      prediction.
AB  - Multiple sequence alignments have much to offer to the understanding of protein
      structure, evolution and function. We are developing approaches to use this
      information in predicting protein-binding specificity, intra-protein and protein
      protein interactions, and in reconstructing protein interaction networks.

PMID- 18629078
TI  - The 4th Bologna Winter School: hot topics in structural genomics.
AB  - The 4th Bologna Winter School on Biotechnologies was held on 9-15 February 2003
      at the University of Bologna, Italy, with the specific aim of discussing recent
      developments in bioinformatics. The school provided an opportunity for students
      and scientists to debate current problems in computational biology and possible
      solutions. The course, co-supported (as last year) by the European Science
      Foundation program on Functional Genomics, focused mainly on hot topics in
      structural genomics, including recent CASP and CAPRI results, recent and
      promising genomewide predictions, protein-protein and protein-DNA interaction
      predictions and genome functional annotation. The topics were organized into four
      main sections (http://www.biocomp.unibo.it).

PMID- 18629079
TI  - In silico identification of functional protein interfaces.
AB  - Proteins perform many of their biological roles through protein-protein, protein
      DNA or protein-ligand interfaces. The identification of the amino acids
      comprising these interfaces often enhances our understanding of the biological
      function of the proteins. Many methods for the detection of functional interfaces
      have been developed, and large-scale analyses have provided assessments of their
      accuracy. Among them are those that consider the size of the protein interface,
      its amino acid composition and its physicochemical and geometrical properties.
      Other methods to this effect use statistical potential functions of pairwise
      interactions, and evolutionary information. The rationale of the evolutionary
      approach is that functional and structural constraints impose selective pressure;
      hence, biologically important interfaces often evolve at a slower pace than do
      other external regions of the protein. Recently, an algorithm, Rate4Site, and a
      web-server, ConSurf (http://consurf.tau.ac.il/), for the identification of
      functional interfaces based on the evolutionary relations among homologous
      proteins as reflected in phylogenetic trees, were developed in our laboratory.
      The explicit use of the tree topology and branch lengths makes the method
      remarkably accurate and sensitive. Here we demonstrate its potency in the
      identification of the functional interfaces of a hypothetical protein, the
      structure of which was determined as part of the international structural
      genomics effort. Finally, we propose to combine complementary procedures, in
      order to enhance the overall performance of methods for the identification of
      functional interfaces in proteins.

PMID- 18629080
TI  - Ab initio protein structure prediction using pathway models.
AB  - Ab initio prediction is the challenging attempt to predict protein structures
      based only on sequence information and without using templates. It is often
      divided into two distinct sub-problems: (a) the scoring function that can
      distinguish native, or native-like structures, from non-native ones; and (b) the
      method of searching the conformational space. Currently, there is no reliable
      scoring function that can always drive a search to the native fold, and there is
      no general search method that can guarantee a significant sampling of near
      natives. Pathway models combine the scoring function and the search. In this
      short review, we explore some of the ways pathway models are used in folding, in
      published works since 2001, and present a new pathway model, HMMSTR-CM, that uses
      a fragment library and a set of nucleation/propagation-based rules. The new
      method was used for ab initio predictions as part of CASP5. This work was
      presented at the Winter School in Bioinformatics, Bologna, Italy, 10-14 February
      2003.

PMID- 18629081
TI  - Development of computational tools for the inference of protein interaction
      specificity rules and functional annotation using structural information.
AB  - Relatively few protein structures are known, compared to the enormous amount of
      sequence data produced in the sequencing of different genomes, and relatively few
      protein complexes are deposited in the PDB with respect to the great amount of
      interaction data coming from high-throughput experiments (two-hybrid or affinity
      purification of protein complexes and mass spectrometry). Nevertheless, we can
      rely on computational techniques for the extraction of high-quality and
      information-rich data from the known structures and for their spreading in the
      protein sequence space. We describe here the ongoing research projects in our
      group: we analyse the protein complexes stored in the PDB and, for each complex
      involving one domain belonging to a family of interaction domains for which some
      interaction data are available, we can calculate its probability of interaction
      with any protein sequence. We analyse the structures of proteins encoding a
      function specified in a PROSITE pattern, which exhibits relatively low
      selectivity and specificity, and build extended patterns. To this aim, we
      consider residues that are well-conserved in the structure, even if their
      conservation cannot easily be recognized in the sequence alignment of the
      proteins holding the function. We also analyse protein surface regions and,
      through the annotation of the solvent-exposed residues, we annotate protein
      surface patches via a structural comparison performed with stringent parameters
      and independently of the residue order in the sequence. Local surface comparison
      may also help in identifying new sequence patterns, which could not be
      highlighted with other sequence-based methods.

PMID- 18629084
TI  - Microarray probe expression measures, data normalization and statistical
      validation.
AB  - DNA microarray technology is a high-throughput method for gaining information on
      gene function. Microarray technology is based on deposition/synthesis, in an
      ordered manner, on a solid surface, of thousands of EST
      sequences/genes/oligonucleotides. Due to the high number of generated datapoints,
      computational tools are essential in microarray data analysis and mining to grasp
      knowledge from experimental results. In this review, we will focus on some of the
      methodologies actually available to define gene expression intensity measures,
      microarray data normalization, and statistical validation of differential
      expression.

PMID- 18629082
TI  - Functional genomics via metabolic footprinting: monitoring metabolite secretion
      by Escherichia coli tryptophan metabolism mutants using FT-IR and direct
      injection electrospray mass spectrometry.
AB  - We sought to test the hypothesis that mutant bacterial strains could be
      discriminated from each other on the basis of the metabolites they secrete into
      the medium (their 'metabolic footprint'), using two methods of 'global'
      metabolite analysis (FT-IR and direct injection electrospray mass spectrometry).
      The biological system used was based on a published study of Escherichia coli
      tryptophan mutants that had been analysed and discriminated by Yanofsky and
      colleagues using transcriptome analysis. Wild-type strains supplemented with
      tryptophan or analogues could be discriminated from controls using FT-IR of 24 h
      broths, as could each of the mutant strains in both minimal and supplemented
      media. Direct injection electrospray mass spectrometry with unit mass resolution
      could also be used to discriminate the strains from each other, and had the
      advantage that the discrimination required the use of just two or three masses in
      each case. These were determined via a genetic algorithm. Both methods are rapid,
      reagentless, reproducible and cheap, and might beneficially be extended to the
      analysis of gene knockout libraries.

PMID- 18629085
TI  - Comparative modelling techniques: where are we?
AB  - The enormous increase in data availability brought about by genomic projects is
      paralleled by an equally unprecedented increase in the expectations for new
      medical, pharmacological, environmental and biotechnological discoveries. Whether
      or not we will be able to meet (at least partially) these expectations will
      depend on how well we will be able to interpret the data and translate the mono
      dimensional information encrypted in genomes into a detailed understanding of its
      biological meaning at the phenotypic level. The process is far from being
      trivial, and the obstacles along the road are formidable: even the problem of
      identifying coding regions in eukaryotic genomes is not completely solved. Far
      more complex is identification of the function of the encoded proteins, and this
      will probably represent the most challenging problem for the next generations of
      scientists.

PMID- 18629086
TI  - The prediction of membrane protein structure and genome structural annotation.
AB  - New methods, essentially based on hidden Markov models (HMM) and neural networks
      (NN), can predict the topography of both beta-barrel and all-alpha membrane
      proteins with high accuracy and a low rate of false positives and false
      negatives. These methods have been integrated in a suite of programs to filter
      proteomes of Gram-negative bacteria, searching for new membrane proteins.

PMID- 18629089
TI  - Some tools and methodologies for domain ontology building.

PMID- 18629088
TI  - Understanding and predicting protein assemblies with 3D structures.
AB  - Protein interactions are central to most biological processes, and are currently
      the subject of great interest. Yet despite the many recently developed methods
      for interaction discovery, little attention has been paid to one of the best
      sources of data: complexes of known three-dimensional (3D) structure. Here we
      discuss how such complexes can be used to study and predict protein interactions
      and complexes, and to interrogate interaction networks proposed by methods such
      as two-hybrid screens or affinity purifications.

PMID- 18629090
TI  - The European Conference on Computational Biology 2002.

PMID- 18629091
TI  - Standards and ontologies for functional genomics: towards unified ontologies for
      biology and biomedicine.

PMID- 18629092
TI  - Developing a protein-interactions ontology.

PMID- 18629093
TI  - The MGED ontology: a framework for describing functional genomics experiments.
AB  - The Microarray Gene Expression Data (MGED) society was formed with an initial
      focus on experiments involving microarray technology. Despite the diversity of
      applications, there are common concepts used and a common need to capture
      experimental information in a standardized manner. In building the MGED ontology,
      it was recognized that it would be impractical to cover all the different types
      of experiments on all the different types of organisms by listing and defining
      all the types of organisms and their properties. Our solution was to create a
      framework for describing microarray experiments with an initial focus on the
      biological sample and its manipulation. For concepts that are common for many
      species, we could provide a manageable listing of controlled terms. For concepts
      that are species-specific or whose values cannot be readily listed, we created an
      'OntologyEntry' concept that referenced an external resource. The MGED ontology
      is a work in progress that needs additional instances and particularly needs
      constraints to be added. The ontology currently covers the experimental sample
      and design, and we have begun capturing aspects of the microarrays themselves as
      well. The primary application of the ontology will be to develop forms for
      entering information into databases, and consequently allowing queries, taking
      advantage of the structure provided by the ontology. The application of an
      ontology of experimental conditions extends beyond microarray experiments and, as
      the scope of MGED includes other aspects of functional genomics, so too will the
      MGED ontology.

PMID- 18629094
TI  - A relational database for the discovery of genes encoding amino acid biosynthetic
      enzymes in pathogenic fungi.
AB  - Fungal phytopathogens continue to cause major economic impact, either directly,
      through crop losses, or due to the costs of fungicide application. Attempts to
      understand these organisms are hampered by a lack of fungal genome sequence data.
      A need exists, however, to develop specific bioinformatics tools to collate and
      analyse the sequence data that currently is available. A web-accessible gene
      discovery database (http://cogeme.ex.ac.uk/biosynthesis.html) was developed as a
      demonstration tool for the analysis of metabolic and signal transduction pathways
      in pathogenic fungi using incomplete gene inventories. Using Bayesian probability
      to analyse the currently available gene information from pathogenic fungi, we
      provide evidence that the obligate pathogen Blumeria graminis possesses all amino
      acid biosynthetic pathways found in free-living fungi, such as Saccharomyces
      cerevisiae. Phylogenetic analysis was also used to deduce a gene history of
      succinate-semialdehyde dehydrogenase, an enzyme in the glutamate and lysine
      biosynthesis pathways. The database provides a tool and methodology to
      researchers to direct experimentation towards predicting pathway conservation in
      pathogenic microorganisms.

PMID- 18629096
TI  - The S. Cerevisiae HAP complex, a key regulator of mitochondrial function,
      coordinates nuclear and mitochondrial gene expression.
AB  - We have compared Saccharomyces cerevisiae global gene expression in wild-type and
      mutants (Deltahap2 and Deltahap4) of the HAP transcriptional complex, which has
      been shown to be necessary for growth on respiratory substrates. Several hundred
      ORFs are under positive or negative control of this complex and we analyse here
      in detail the effect of HAP on mitochondria. We found that most of the genes
      upregulated in the wild-type strain were involved in organelle functions, but
      practically none of the downregulated ones. Nuclear genes encoding the different
      subunits of the respiratory chain complexes figure in the genes more expressed in
      the wild-type than in the mutants, as expected, but in this group we also found
      key components of the mitochondrial translation apparatus. This control of
      mitochondrial translation may be one of the means of coordinating mitochondrial
      and nuclear gene expression in elaborating the respiratory chain. In addition,
      HAP controls the nuclear genes involved in several other mitochondrial processes
      (import, mitochondrial division) that define the metabolic state of the cell, but
      not mitochondrial DNA replication and transcription. In most cases, a putative
      CCAAT-binding site is present upstream of the ORF, while in others no such sites
      are present, suggesting the control to be indirect. The large number of genes
      regulated by the HAP complex, as well as the fact that HAP also regulates some
      putative transcriptional activators of unknown function, place this complex at a
      hierarchically high position in the global transcriptional regulation of the
      cell.

PMID- 18629097
TI  - An approach to inferring transcriptional regulation among genes from large-scale
      expression data.
AB  - The use of DNA microarrays opens up the possibility of measuring the expression
      levels of thousands of genes simultaneously under different conditions. Time
      course experiments allow researchers to study the dynamics of gene interactions.
      The inference of genetic networks from such measures can give important insights
      for the understanding of a variety of biological problems. Most of the existing
      methods for genetic network reconstruction require many experimental data points,
      or can only be applied to the reconstruction of small subnetworks. Here we
      present a method that reduces the dimensionality of the dataset and then extracts
      the significant dynamic correlations among genes. The method requires a number of
      points achievable in common time-course experiments.

PMID- 18629098
TI  - Building a cell and anatomy ontology of Caenorhabditis elegans.
AB  - We are endowed with a rich knowledge about Caenorhabditis elegans. Its
      stereotyped anatomy and development has stimulated research and resulted in the
      accumulation of cell-based information concerning gene expression, and the role
      of specific cells in developmental signalling and behavioural circuits. To make
      the information more accessible to sophisticated queries and automated retrieval
      systems, WormBase has begun to construct a C. elegans cell and anatomy ontology.
      Here we present our strategies and progress.

PMID- 18629099
TI  - Bringing ontology to the gene ontology.
AB  - We present an analysis of some considerations involved in expressing the Gene
      Ontology (GO) as a machine-processible ontology, reflecting principles of formal
      ontology. GO is a controlled vocabulary that is intended to facilitate
      communication between biologists by standardizing usage of terms in database
      annotations. Making such controlled vocabularies maximally useful in support of
      bioinformatics applications requires explicating in machine-processible form the
      implicit background information that enables human users to interpret the meaning
      of the vocabulary terms. In the case of GO, this process would involve rendering
      the meanings of GO into a formal (logical) language with the help of domain
      experts, and adding additional information required to support the chosen
      formalization. A controlled vocabulary augmented in these ways is commonly called
      an ontology. In this paper, we make a modest exploration to determine the
      ontological requirements for this extended version of GO. Using the terms within
      the three GO hierarchies (molecular function, biological process and cellular
      component), we investigate the facility with which GO concepts can be
      ontologized, using available tools from the philosophical and ontological
      engineering literature.

PMID- 18629100
TI  - Early gene expression in wounded human keratinocytes revealed by DNA microarray
      analysis.
AB  - Wound healing involves several steps: spreading of the cells, migration and
      proliferation. We have profiled gene expression during the early events of wound
      healing in normal human keratinocytes with a home-made DNA microarray containing
      about 1000 relevant human probes. An original wounding machine was used, that
      allows the wounding of up to 40% of the surface of a confluent monolayer of
      cultured cells grown on a Petri dish (compared with 5% with a classical 'scratch'
      method). The two aims of the present study were: (a) to validate a limited number
      of genes by comparing the expression levels obtained with this technique with
      those found in the literature; (b) to combine the use of the wounding machine
      with DNA microarray analysis for large-scale detection of the molecular events
      triggered during the early stages of the wound-healing process. The time-courses
      of RNA expression observed at 0.5, 1.5, 3, 6 and 15 h after wounding for genes
      such as c-Fos, c-Jun, Egr1, the plasminogen activator PLAU (uPA) and the signal
      transducer and transcription activator STAT3, were consistent with previously
      published data. This suggests that our methodologies are able to perform
      quantitative measurement of gene expression. Transcripts encoding two zinc finger
      proteins, ZFP36 and ZNF161, and the tumour necrosis factor alpha-induced protein
      TNFAIP3, were also overexpressed after wounding. The role of the p38 mitogen
      activated protein kinase (p38MAPK) in wound healing was shown after the
      inhibition of p38 by SB203580, but our results also suggest the existence of
      surrogate activating pathways.

PMID- 18629101
TI  - The semantic web--new ways to present and integrate information.

PMID- 18629102
TI  - The HUPO Proteomics Standards Initiative Meeting: Towards Common Standards for
      Exchanging Proteomics Data.
AB  - The Proteomics Standards Initiative (PSI) aims to define community standards for
      data representation in proteomics and to facilitate data comparison, exchange and
      verification. Initially the fields of protein-protein interactions (PPI) and mass
      spectroscopy have been targeted and the inaugural meeting of the PSI addressed
      the questions of data storage and exchange in both of these areas. The PPI group
      rapidly reached consensus as to the minimum requirements for a data exchange
      model; an XML draft is now being produced. The mass spectroscopy group have
      achieved major advances in the definition of a required data model and working
      groups are currently taking these discussions further. A further meeting is
      planned in January 2003 to advance both these projects.

PMID- 18629103
TI  - The Gene Ontology Annotation (GOA) Project--Application of GO in SWISS-PROT,
      TrEMBL and InterPro.

PMID- 18629104
TI  - The ESF Programme on 'Integrated Approaches to Functional Genomics'. Workshop on
      'Ontology for Biology'.

PMID- 18629105
TI  - Why chloroplasts and mitochondria contain genomes.
AB  - Chloroplasts and mitochondria originated as bacterial symbionts. The larger, host
      cells acquired genetic information from their prokaryotic guests by lateral gene
      transfer. The prokaryotically-derived genes of the eukaryotic cell nucleus now
      function to encode the great majority of chloroplast and mitochondrial proteins,
      as well as many proteins of the nucleus and cytosol. Genes are copied and moved
      between cellular compartments with relative ease, and there is no established
      obstacle to successful import of any protein precursor from the cytosol. Yet
      chloroplasts and mitochondria have not abdicated all genes and gene expression to
      the nucleus and to cytosolic translation. What, then, do chloroplast- and
      mitochondrially-encoded proteins have in common that confers a selective
      advantage on the cytoplasmic location of their genes? The proposal advanced here
      is that co-location of chloroplast and mitochondrial genes with their gene
      products is required for rapid and direct regulatory coupling. Redox control of
      gene expression is suggested as the common feature of those chloroplast and
      mitochondrial proteins that are encoded in situ. Recent evidence is consistent
      with this hypothesis, and its underlying assumptions and predictions are
      described.

PMID- 18629106
TI  - ESF Programme on 'Integrated Approaches for Functional Genomics' Workshop on
      'Modelling of Molecular Networks'.

PMID- 18629107
TI  - How a philosophical theory of causation may help in ontological engineering.

PMID- 18629108
TI  - Attractive models: how to make the silicon cell relevant and dynamic.

PMID- 18629109
TI  - An upper-level ontology for the biomedical domain.
AB  - At the US National Library of Medicine we have developed the Unified Medical
      Language System (UMLS), whose goal it is to provide integrated access to a large
      number of biomedical resources by unifying the vocabularies that are used to
      access those resources. The UMLS currently interrelates some 60 controlled
      vocabularies in the biomedical domain. The UMLS coverage is quite extensive,
      including not only many concepts in clinical medicine, but also a large number of
      concepts applicable to the broad domain of the life sciences. In order to provide
      an overarching conceptual framework for all UMLS concepts, we developed an upper
      level ontology, called the UMLS semantic network. The semantic network, through
      its 134 semantic types, provides a consistent categorization of all concepts
      represented in the UMLS. The 54 links between the semantic types provide the
      structure for the network and represent important relationships in the biomedical
      domain. Because of the growing number of information resources that contain
      genetic information, the UMLS coverage in this area is being expanded. We
      recently integrated the taxonomy of organisms developed by the NLM's National
      Center for Biotechnology Information, and we are currently working together with
      the developers of the Gene Ontology to integrate this resource, as well. As
      additional, standard, ontologies become publicly available, we expect to
      integrate these into the UMLS construct.

PMID- 18629110
TI  - Automatic classification of protein functions from the literature.

PMID- 18629111
TI  - Genomics and ethics: the case of cloned and/or transgenic animals.
AB  - The point of the present study is to illustrate and, if possible, promote the
      existing link between genomics and ethics, taking the example of cloned and
      transgenic animals. These 'new animals' raise theoretical and practical problems
      that concern applied ethics. We will explore more particularly an original
      strategy showing that it is possible, starting from philosophical questioning
      about the nature of identity, to use a genomic approach, based on amplification
      fragment length polymorphism (AFLP) and methylation-sensitive amplification
      polymorphism (MSAP) detection, to provide useful tools to define more rigorously
      what cloned animals are, by testing their genetic and epigenetic identity. We
      expect from the future results of this combined approach to stimulate the
      creativity of the philosophical and ethical reflection about the impact of
      biotechnology on animals, and to increase scientific involvement in such issues.

PMID- 18629112
TI  - Turning informal thesauri into formal ontologies: a feasibility study on
      biomedical knowledge re-use.
AB  - This paper reports a large-scale knowledge conversion and curation experiment.
      Biomedical domain knowledge from a semantically weak and shallow terminological
      resource, the UMLS, is transformed into a rigorous description logics format.
      This way, the broad coverage of the UMLS is combined with inference mechanisms
      for consistency and cycle checking. They are the key to proper cleansing of the
      knowledge directly imported from the UMLS, as well as subsequent updating,
      maintenance and refinement of large knowledge repositories. The emerging
      biomedical knowledge base currently comprises more than 240 000 conceptual
      entities and hence constitutes one of the largest formal knowledge repositories
      ever built.

PMID- 18629114
TI  - Building ontologies in DAML + OIL.
AB  - In this article we describe an approach to representing and building ontologies
      advocated by the Bioinformatics and Medical Informatics groups at the University
      of Manchester. The hand-crafting of ontologies offers an easy and rapid avenue to
      delivering ontologies. Experience has shown that such approaches are
      unsustainable. Description logic approaches have been shown to offer
      computational support for building sound, complete and logically consistent
      ontologies. A new knowledge representation language, DAML + OIL, offers a new
      standard that is able to support many styles of ontology, from hand-crafted to
      full logic-based descriptions with reasoning support. We describe this language,
      the OilEd editing tool, reasoning support and a strategy for the language's use.
      We finish with a current example, in the Gene Ontology Next Generation (GONG)
      project, that uses DAML + OIL as the basis for moving the Gene Ontology from its
      current hand-crafted, form to one that uses logical descriptions of a concept's
      properties to deliver a more complete version of the ontology.

PMID- 18629113
TI  - Pressures in archaeal protein coding genes: a comparative study.
AB  - Our studies on the bases of codons from 11 completely sequenced archaeal genomes
      show that, as we move from GC-rich to AT-rich protein-coding gene-containing
      species, the differences between G and C and between A and T, the purine load (AG
      content), and also the overall persistence (i.e. the tendency of a base to be
      followed by the same base) within codons, all increase almost simultaneously,
      although the extent of increase is different over the three positions within
      codons. These findings suggest that the deviations from the second parity rule
      (through the increasing differences between complementary base contents) and the
      increasing purine load hinder the chance of formation of the intra-strand Watson
      Crick base-paired secondary structures in mRNAs (synonymous with the protein
      coding genes we dealt with), thereby increasing the translational efficiency. We
      hypothesize that the ATrich protein-coding gene-containing archaeal species might
      have better translational efficiency than their GC-rich counterparts.

PMID- 18629115
TI  - On the MIAME Standards and Central Repositories of Microarray Data.

PMID- 18629116
TI  - Proteomic analysis of legume-microbe interactions.

PMID- 18629119
TI  - Advances in pig genomics and functional gene discovery.
AB  - Advances in pig gene identification, mapping and functional analysis have
      continued to make rapid progress. The porcine genetic linkage map now has nearly
      3000 loci, including several hundred genes, and is likely to expand considerably
      in the next few years, with many more genes and amplified fragment length
      polymorphism (AFLP) markers being added to the map. The physical genetic map is
      also growing rapidly and has over 3000 genes and markers. Several recent
      quantitative trait loci (QTL) scans and candidate gene analyses have identified
      important chromosomal regions and individual genes associated with traits of
      economic interest. The commercial pig industry is actively using this information
      and traditional performance information to improve pig production by marker
      assisted selection (MAS). Research to study the co-expression of thousands of
      genes is now advancing and methods to combine these approaches to aid in gene
      discovery are under way. The pig's role in xenotransplantation and biomedical
      research makes the study of its genome important for the study of human disease.
      This review will briefly describe advances made, directions for future research
      and the implications for both the pig industry and human health.

PMID- 18629120
TI  - MetNet: Software to Build and Model the Biogenetic Lattice of Arabidopsis.
AB  - MetNet (http://www.botany.iastate.edu/ approximately
      mash/metnetex/metabolicnetex.html) is publicly available software in development
      for analysis of genome-wide RNA, protein and metabolite profiling data. The
      software is designed to enable the biologist to visualize, statistically analyse
      and model a metabolic and regulatory network map of Arabidopsis, combined with
      gene expression profiling data. It contains a JAVA interface to an interactions
      database (MetNetDB) containing information on regulatory and metabolic
      interactions derived from a combination of web databases (TAIR, KEGG, BRENDA) and
      input from biologists in their area of expertise. FCModeler captures input from
      MetNetDB in a graphical form. Sub-networks can be identified and interpreted
      using simple fuzzy cognitive maps. FCModeler is intended to develop and evaluate
      hypotheses, and provide a modelling framework for assessing the large amounts of
      data captured by high-throughput gene expression experiments. FCModeler and
      MetNetDB are currently being extended to three-dimensional virtual reality
      display. The MetNet map, together with gene expression data, can be viewed using
      multivariate graphics tools in GGobi linked with the data analytic tools in R.
      Users can highlight different parts of the metabolic network and see the relevant
      expression data highlighted in other data plots. Multi-dimensional expression
      data can be rotated through different dimensions. Statistical analysis can be
      computed alongside the visual. MetNet is designed to provide a framework for the
      formulation of testable hypotheses regarding the function of specific genes, and
      in the long term provide the basis for identification of metabolic and regulatory
      networks that control plant composition and development.

PMID- 18629121
TI  - Progress in Establishing Common Standards for Exchanging Proteomics Data: The
      Second Meeting of the HUPO Proteomics Standards Initiative.
AB  - The Proteomics Standards Initiative (PSI) aims to define community standards for
      data representation in proteomics and to facilitate data comparison, exchange and
      verification. Rapid progress has been made in the development of common standards
      for data exchange in the fields of both mass spectrometry and protein-protein
      interactions since the first PSI meeting [1]. Both hardware and software
      manufacturers have agreed to work to ensure that a proteomics-specific extension
      is created for the emerging ASTM mass spectrometry standard and the data model
      for a proteomics experiment has advanced significantly. The Protein-Protein
      Interactions (PPI) group expects to publish the Level 1 PSI data exchange format
      for protein-protein interactions by early summer this year, and discussion as to
      the additional content of Level 2 has been initiated.

PMID- 18629117
TI  - Current awareness on comparative and functional genomics.

PMID- 18629123
TI  - Towards Interoperability in Genome Databases: The MAtDB (MIPS Arabidopsis
      Thaliana Database) Experience.
AB  - Increasing numbers of whole-genome sequences are available, but to interpret them
      fully requires more than listing all genes. Genome databases are faced with the
      challenges of integrating heterogenous data and enabling data mining. In
      comparison to a data warehousing approach, where integration is achieved through
      replication of all relevant data in a unified schema, distributed approaches
      provide greater flexibility and maintainability. These are important in a field
      where new data is generated rapidly and our understanding of the data changes.
      Interoperability between distributed data sources allows data maintenance to be
      separated from integration and analysis. Simple ways to access the data can
      facilitate the development of new data mining tools and the transition from model
      genome analysis to comparative genomics. With the MIPS Arabidopsis thaliana
      genome database (MAtDB, http://mips.gsf.de/proj/thal/db) our aim is to go beyond
      a data repository towards creating an integrated knowledge resource. To this end,
      the Arabidopsis genome has been a backbone against which to structure and
      integrate heterogenous data. The challenges to be met are continuous updating of
      data, the design of flexible data models that can evolve with new data, the
      integration of heterogenous data, e.g. through the use of ontologies,
      comprehensive views and visualization of complex information, simple interfaces
      for application access locally or via the Internet, and knowledge transfer across
      species.

PMID- 18629122
TI  - Genomics and mapping of teleostei (bony fish).
AB  - Until recently, the Human Genome Project held centre stage in the press releases
      concerning sequencing programmes. However, in October 2001, it was announced that
      the Japanese puffer fish (Takifugu rubripes, Fugu) was the second vertebrate
      organism to be sequenced to draft quality. Briefly, the spotlight was on fish
      genomes. There are currently two other fish species undergoing intensive
      sequencing, the green spotted puffer fish (Tetraodon nigroviridis) and the
      zebrafish (Danio rerio). But this trio are, in many ways, atypical
      representations of the current state of fish genomic research. The aim of this
      brief review is to demonstrate the complexity of fish as a group of vertebrates
      and to publicize the 'lesser-known' species, all of which have something to
      offer.

PMID- 18629124
TI  - Fifty years of the double helix.

PMID- 18629125
TI  - USDA Stakeholder Workshop on Animal Bioinformatics: Summary and Recommendations.
AB  - An electronic workshop was conducted on 4 November-13 December 2002 to discuss
      current issues and needs in animal bioinformatics. The electronic (e-mail
      listserver) format was chosen to provide a relatively speedy process that is
      broad in scope, cost-efficient and easily accessible to all participants.
      Approximately 40 panelists with diverse species and discipline expertise
      communicated through the panel e-mail listserver. The panel included scientists
      from academia, industry and government, in the USA, Australia and the UK. A
      second 'stakeholder' e-mail listserver was used to obtain input from a broad
      audience with general interests in animal genomics. The objectives of the
      electronic workshop were: (a) to define priorities for animal genome database
      development; and (b) to recommend ways in which the USDA could provide leadership
      in the area of animal genome database development. E-mail messages from panelists
      and stakeholders are archived at http://genome.cvm.umn.edu/bioinfo/. Priorities
      defined for animal genome database development included: (a) data repository; (b)
      tools for genome analysis; (c) annotation; (d) practical application of genomic
      data; and (e) a biological framework for DNA sequence. A stable source of
      funding, such as the USDA Agricultural Research Service (ARS), was recommended to
      support maintenance of data repositories and data curation. Continued support for
      competitive grants programs within the USDA Cooperative State Research, Education
      and Extension Service (CSREES) was recommended for tool development and
      hypothesis-driven research projects in genome analysis. Additional stakeholder
      input will be required to continuously refine priorities and maximize the use of
      limited resources for animal bioinformatics within the USDA.

PMID- 18629126
TI  - A review of catfish genomics: progress and perspectives.
AB  - Catfish is one of the lower teleosts whose genome research is important for
      evolutionary genomics. As the major aquaculture species in the USA, its genome
      research also has practical and economical implications. Much progress has been
      made in recent years, including the development of large numbers of molecular
      markers, the construction of framework genetic linkage maps, the identification
      of putative markers involved in performance traits, and the development of
      genomic resources. Repetitive elements have been identified and characterized in
      the catfish genome that should facilitate physical analysis of the catfish
      genome. A large number of genes or full-length cDNAs have been analysed using
      genomic approaches, providing information on gene structure, gene evolution and
      gene expression in relation to functions. Catfish genome research has come to a
      stage when physical mapping through BAC contig construction is greatly demanded,
      in order to develop regional markers for QTL analysis and for large-scale
      comparative mapping. The current effort in large-scale EST analysis and type I
      marker mapping should further enhance research efficiency through comparative
      mapping. Candidate gene identification is being accelerated through the use of
      cDNA microarrays.

PMID- 18629127
TI  - Report on the forest trees workshop at the plant and animal genome conference.

PMID- 18629128
TI  - Caenorhabditis elegans-applications to nematode genomics.
AB  - The complete genome sequence of the free-living nematode Caenorhabditis elegans
      was published 4 years ago. Since then, we have seen great strides in technologies
      that seek to exploit this data. Here we describe the application of some of these
      techniques and other advances that are helping us to understand about not only
      the biology of this important model organism but also the entire phylum Nematoda.

PMID- 18629129
TI  - Gene selection in arthritis classification with large-scale microarray expression
      profiles.
AB  - The use of large-scale microarray expression profiling to identify predictors of
      disease class has become of major interest. Beyond their impact in the clinical
      setting (i.e. improving diagnosis and treatment), these markers are also likely
      to provide clues on the molecular mechanisms underlining the diseases. In this
      paper we describe a new method for the identification of multiple gene predictors
      of disease class. The method is applied to the classification of two forms of
      arthritis that have a similar clinical endpoint but different underlying
      molecular mechanisms: rheumatoid arthritis (RA) and osteoarthritis (OA). We aim
      at both the classification of samples and the location of genes characterizing
      the different classes. We achieve both goals simultaneously by combining a binary
      probit model for classification with Bayesian variable selection methods to
      identify important genes.We find very small sets of genes that lead to good
      classification results. Some of the selected genes are clearly correlated with
      known aspects of the biology of arthritis and, in some cases, reflect already
      known differences between RA and OA.

PMID- 18629130
TI  - Development of a maize molecular evolutionary genomic database.
AB  - PANZEA is the first public database for studying maize genomic diversity. It was
      initiated as a repository of genomic diversity for an NSF Plant Genome project on
      'Maize Evolutionary Genomics'. PANZEA is hosted at the Bioinformatics Research
      Center, North Carolina State University, and is open to the public
      (http://statgen.ncsu.edu/panzea). PANZEA is designed to capture the
      interrelationships between germplasm, molecular diversity, phenotypic diversity
      and genome structure. It has the ability to store, integrate and visualize DNA
      sequence, enzymatic, SSR (simple sequence repeat) marker, germplasm and
      phenotypic data. The relational data model is selected and implemented in Oracle.
      An automated DNA sequence data submission tool has been created that allows
      project researchers to remotely submit their DNA sequence data directly to
      PANZEA. On-line database search forms and reports have been created to allow
      users to search or download germplasm, DNA sequence, gene/locus data and much
      more, directly from the web.

PMID- 18629131
TI  - Global analysis of cell type-specific gene expression.
AB  - The tissues and organs of multicellular eukaryotes are frequently observed to
      comprise complex three-dimensional interspersions of different cell types. It is
      a reasonable assumption that different global patterns of gene expression are
      found within these different cell types. This review outlines general
      experimental strategies designed to characterize these global gene expression
      patterns, based on a combination of methods of transgenic fluorescent protein
      (FP) expression and targeting, of flow cytometry and sorting and of high
      throughput gene expression analysis.

PMID- 18629132
TI  - Specialized hidden markov model databases for microbial genomics.
AB  - As hidden Markov models (HMMs) become increasingly more important in the analysis
      of biological sequences, so too have databases of HMMs expanded in size, number
      and importance. While the standard paradigm a short while ago was the analysis of
      one or a few sequences at a time, it has now become standard procedure to submit
      an entire microbial genome. In the future, it will be common to submit large
      groups of completed genomes to run simultaneously against a dozen public
      databases and any number of internally developed targets. This paper looks at
      some of the readily available HMM (or HMM-like) algorithms and several publicly
      available HMM databases, and outlines methods by which the reader may develop
      custom HMM targets.

PMID- 18629133
TI  - Emerging use of gene expression microarrays in plant physiology.
AB  - Microarrays have become an important technology for the global analysis of gene
      expression in humans, animals, plants, and microbes. Implemented in the context
      of a well-designed experiment, cDNA and oligonucleotide arrays can provide
      highthroughput, simultaneous analysis of transcript abundance for hundreds, if
      not thousands, of genes. However, despite widespread acceptance, the use of
      microarrays as a tool to better understand processes of interest to the plant
      physiologist is still being explored. To help illustrate current uses of
      microarrays in the plant sciences, several case studies that we believe
      demonstrate the emerging application of gene expression arrays in plant
      physiology were selected from among the many posters and presentations at the
      2003 Plant and Animal Genome XI Conference. Based on this survey, microarrays are
      being used to assess gene expression in plants exposed to the experimental
      manipulation of air temperature, soil water content and aluminium concentration
      in the root zone. Analysis often includes characterizing transcript profiles for
      multiple post-treatment sampling periods and categorizing genes with common
      patterns of response using hierarchical clustering techniques. In addition,
      microarrays are also providing insights into developmental changes in gene
      expression associated with fibre and root elongation in cotton and maize,
      respectively. Technical and analytical limitations of microarrays are discussed
      and projects attempting to advance areas of microarray design and data analysis
      are highlighted. Finally, although much work remains, we conclude that
      microarrays are a valuable tool for the plant physiologist interested in the
      characterization and identification of individual genes and gene families with
      potential application in the fields of agriculture, horticulture and forestry.

PMID- 18629134
TI  - The SOFG Anatomy Entry List (SAEL): an annotation tool for functional genomics
      data.
AB  - A great deal of data in functional genomics studies needs to be annotated with
      low-resolution anatomical terms. For example, gene expression assays based on
      manually dissected samples (microarray, SAGE, etc.) need high-level anatomical
      terms to describe sample origin. First-pass annotation in high-throughput assays
      (e.g. large-scale in situ gene expression screens or phenotype screens) and
      bibliographic applications, such as selection of keywords, would also benefit
      from a minimum set of standard anatomical terms. Although only simple terms are
      required, the researcher faces serious practical problems of inconsistency and
      confusion, given the different aims and the range of complexity of existing
      anatomy ontologies. A Standards and Ontologies for Functional Genomics (SOFG)
      group therefore initiated discussions between several of the major anatomical
      ontologies for higher vertebrates. As we report here, one result of these
      discussions is a simple, accessible, controlled vocabulary of gross anatomical
      terms, the SOFG Anatomy Entry List (SAEL). The SAEL is available from
      http://www.sofg.org and is intended as a resource for biologists, curators,
      bioinformaticians and developers of software supporting functional genomics. It
      can be used directly for annotation in the contexts described above. Importantly,
      each term is linked to the corresponding term in each of the major anatomy
      ontologies. Where the simple list does not provide enough detail or
      sophistication, therefore, the researcher can use the SAEL to choose the
      appropriate ontology and move directly to the relevant term as an entry point.
      The SAEL links will also be used to support computational access to the
      respective ontologies.

PMID- 18629135
TI  - Identification of a core set of genes that signifies pathways underlying cardiac
      hypertrophy.
AB  - Although the molecular signals underlying cardiac hypertrophy have been the
      subject of intense investigation, the extent of common and distinct gene
      regulation between different forms of cardiac hypertrophy remains unclear. We
      hypothesized that a general and comparative analysis of hypertrophic gene
      expression, using microarray technology in multiple models of cardiac
      hypertrophy, including aortic banding, myocardial infarction, an arteriovenous
      shunt and pharmacologically induced hypertrophy, would uncover networks of
      conserved hypertrophy-specific genes and identify novel genes involved in
      hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46)
      of rat ventricular RNA, we identified a core set of 139 genes with consistent
      differential expression in all hypertrophy models as compared to their controls,
      including 78 genes not previously associated with hypertrophy and 61 genes whose
      altered expression had previously been reported. We identified a single common
      gene program underlying hypertrophic remodelling, regardless of how the
      hypertrophy was induced. These genes constitute the molecular basis for the
      existence of one main form of cardiac hypertrophy and may be useful for
      prediction of a common therapeutic approach. Supplementary material for this
      article can be found at: http://www.interscience.wiley.com/jpages/1531
      6912/suppmat.

PMID- 18629136
TI  - Ontologies for the description of mouse phenotypes.
AB  - Ontologies are becoming increasingly important for the efficient storage,
      retrieval and mining of biological data. The description of phenotypes using
      ontologies is a particularly complex problem. We outline a schema that can be
      used to describe phenotypes by combining orthologous axiomatic ontologies. We
      also describe tools for storing, browsing and searching such complex ontologies.
      Central to this approach is that assays (protocols for measuring phenotypic
      characters) describe what has been measured as well as how this was done,
      allowing assays to link individual organisms to ontologies describing phenotypes.
      We have evaluated this approach by automatically annotating data on 600,000
      mutant mice phenotypes using the SHIRPA protocol. We believe this approach will
      enable the flexible, extensible and detailed description of phenotypes from any
      organism.

PMID- 18629137
TI  - Ontology for genome comparison and genomic rearrangements.
AB  - We present an ontology for describing genomes, genome comparisons, their
      evolution and biological function. This ontology will support the development of
      novel genome comparison algorithms and aid the community in discussing genomic
      evolution. It provides a framework for communication about comparative genomics,
      and a basis upon which further automated analysis can be built. The nomenclature
      defined by the ontology will foster clearer communication between biologists, and
      also standardize terms used by data publishers in the results of analysis
      programs. The overriding aim of this ontology is the facilitation of consistent
      annotation of genomes through computational methods, rather than human
      annotators. To this end, the ontology includes definitions that support computer
      analysis and automated transfer of annotations between genomes, rather than
      relying upon human mediation.

PMID- 18629138
TI  - A special section of articles from the 7 annual bio-ontologies meeting
      "Ontologies and Bio-Images".

PMID- 18629139
TI  - Biomedical informatics and granularity.
AB  - An explicit formal-ontological representation of entities existing at multiple
      levels of granularity is an urgent requirement for biomedical information
      processing. We discuss some fundamental principles which can form a basis for
      such a representation. We also comment on some of the implicit treatments of
      granularity in currently available ontologies and terminologies (GO, FMA, SNOMED
      CT).

PMID- 18629142
TI  - Workshop--Predicting the structure of biological molecules.
AB  - This April, in Cambridge (UK), principal investigators from the Mathematical
      Biology Group of the Medical Research Council's National Institute of Medical
      Research organized a workshop in structural bioinformatics at the Centre for
      Mathematical Sciences. Bioinformatics researchers of several nationalities from
      labs around the country presented and discussed their computational work in
      biomolecular structure prediction and analysis, and in protein evolution. The
      meeting was intensive and lively and gave attendees an overview of the healthy
      state of protein bioinformatics in the UK.

PMID- 18629143
TI  - Obol: integrating language and meaning in bio-ontologies.
AB  - Ontologies are intended to capture and formalize a domain of knowledge. The
      ontologies comprising the Open Biological Ontologies (OBO) project, which
      includes the Gene Ontology (GO), are formalizations of various domains of
      biological knowledge. Ontologies within OBO typically lack computable definitions
      that serve to differentiate a term from other similar terms. The computer is
      unable to determine the meaning of a term, which presents problems for tools such
      as automated reasoners. Reasoners can be of enormous benefit in managing a
      complex ontology. OBO term names frequently implicitly encode the kind of
      definitions that can be used by computational tools, such as automated reasoners.
      The definitions encoded in the names are not easily amenable to computation,
      because the names are ostensibly natural language phrases designed for human
      users. These names are highly regular in their grammar, and can thus be treated
      as valid sentences in some formal or computable language.With a description of
      the rules underlying this formal language, term names can be parsed to derive
      computable definitions, which can then be reasoned over. This paper describes the
      effort to elucidate that language, called Obol, and the attempts to reason over
      the resulting definitions. The current implementation finds unique non-trivial
      definitions for around half of the terms in the GO, and has been used to find 223
      missing relationships, which have since been added to the ontology. Obol has
      utility as an ontology maintenance tool, and as a means of generating computable
      definitions for a whole ontology.The software is available under an open-source
      license from: http://www.fruitfly. org/~cjm/obol. Supplementary material for this
      article can be found at: http://www. interscience.wiley.com/jpages/1531
      6912/suppmat.

PMID- 18629146
TI  - The molecule role ontology: an ontology for annotation of signal transduction
      pathway molecules in the scientific literature.
AB  - In general, it is not easy to specify a single sequence identity for each
      molecule name that appears in a pathway in the scientific literature. A molecule
      name may stand for concepts of various granularities, from concrete objects such
      as H-Ras and ERK1 to abstract concepts or categories such as Ras and MAPK.
      Typically, the relations among molecule names derive a hierarchical structure;
      without a proper way to handle this knowledge, it becomes ever more difficult to
      develop a reliable pathway database. This paper describes an ontology that is
      designed to annotate molecules in the scientific literature on signal
      transduction pathways.

PMID- 18629145
TI  - Navigating public microarray databases.
AB  - With the ever-escalating amount of data being produced by genome-wide microarray
      studies, it is of increasing importance that these data are captured in public
      databases so that researchers can use this information to complement and enhance
      their own studies. Many groups have set up databases of expression data, ranging
      from large repositories, which are designed to comprehensively capture all
      published data, through to more specialized databases. The public repositories,
      such as ArrayExpress at the European Bioinformatics Institute contain complete
      datasets in raw format in addition to processed data, whilst the specialist
      databases tend to provide downstream analysis of normalized data from more
      focused studies and data sources. Here we provide a guide to the use of these
      public microarray resources.

PMID- 18629147
TI  - The Seventh Annual Bio-Ontologies Meeting Moat House Hotel, Glasgow, 30 July
      2004.
AB  - The Annual Bio-Ontologies Meeting has now reached its seventh consecutive year,
      running as a special interest group (SIG) of the much larger ISMB conference.
      This year's meeting in Glasgow had approximately 100 attendees. Since the advent
      of the Gene Ontology, which coincided with the first Bio-Ontologies Meeting, we
      have seen a year-on-year strengthening of the field; bio-ontologies has moved
      from being dominated by computer science to be led by biological applications;
      discussion is less about 'what is an ontology?' and more about 'how to build an
      ontology which is fit for purpose?'. This strengthening of the field can be seen
      elsewhere. Both the main ISMB conference and this year's Pacific Symposium on
      Biocomputing (PSB) have seen a large number of submissions to their ontologies
      track. For the first time a selection of the papers from the SIG is being
      published in this issue of Comparative and Functional Genomics. We hope that this
      will complement the publications of the larger conferences, bringing to a wider
      audience the cutting edge research that characterizes the Bio-Ontologies SIG.

PMID- 18629148
TI  - Meeting report: the Institute for Genomic Research/Wellcome Trust Conference:
      Genomes 2004 14-17 April 2004, the Wellcome Trust Conference Centre, the Wellcome
      Trust Genome Campus, Hinxton, Cambridge, UK.
AB  - This conference brought the microbial genomics community together to share their
      most up-to-the-minute achievements, so much so that several talks cannot be
      covered here, as the work discussed has not yet been published. This meeting
      report has details of a cross-section of the talks from the sessions on 'Genome
      analysis and comparative genomics', 'Computational genomics' and 'Functional
      genomics', ranging from studies on complex environmental samples, to specific
      pathogenic bacteria, to yeasts.

PMID- 18629150
TI  - A comparison of global gene expression measurement technologies in Arabidopsis
      thaliana.
AB  - Microarrays and tag-based transcriptional profiling technologies represent
      diverse but complementary data types. We are currently conducting a comparison of
      high-density in situ synthesized microarrays and massively-parallel signature
      sequencing (MPSS) data in the model plant, Arabidopsis thaliana. The MPSS data
      (available at http://mpss.udel.edu/at) and the microarray data have been compiled
      using the same RNA source material. In this review, we outline the experimental
      strategy that we are using, and present preliminary data and interpretations from
      the transcriptional profiles of Arabidopsis leaves and roots. The preliminary
      data indicate that the log ratio differences of transcripts between leaves and
      roots measured by microarray data are in better agreement with the MPSS data than
      the absolute intensities measured for individual microarrays hybridized to only
      one of the cRNA populations. The correlation was substantially improved by
      focusing on a subset of genes excluding those with very low expression levels;
      this selection may have removed noisy data. Future reports will incorporate more
      than 10 tissues that have been sampled by MPSS.

PMID- 18629151
TI  - A special section of selected reviews from the Plant & Animal Genome XII
      Conference.

PMID- 18629152
TI  - Creating porcine biomedical models through recombineering.
AB  - Recent advances in genomics provide genetic information from humans and other
      mammals (mouse, rat, dog and primates) traditionally used as models as well as
      new candidates (pigs and cattle). In addition, linked enabling technologies, such
      as transgenesis and animal cloning, provide innovative ways to design and perform
      experiments to dissect complex biological systems. Exploitation of genomic
      information overcomes the traditional need to choose naturally occurring models.
      Thus, investigators can utilize emerging genomic knowledge and tools to create
      relevant animal models. This approach is referred to as reverse genetics. In
      contrast to 'forward genetics', in which gene(s) responsible for a particular
      phenotype are identified by positional cloning (phenotype to genotype), the
      'reverse genetics' approach determines the function of a gene and predicts the
      phenotype of a cell, tissue, or organism (genotype to phenotype). The convergence
      of classical and reverse genetics, along with genomics, provides a working
      definition of a 'genetic model' organism (3). The recent construction of
      phenotypic maps defining quantitative trait loci (QTL) in various domesticated
      species provides insights into how allelic variations contribute to phenotypic
      diversity. Targeted chromosomal regions are characterized by the construction of
      bacterial artificial chromosome (BAC) contigs to isolate and characterize genes
      contributing towards phenotypic variation. Recombineering provides a powerful
      methodology to harvest genetic information responsible for phenotype. Linking
      recombineering with gene-targeted homologous recombination, coupled with nuclear
      transfer (NT) technology can provide 'clones' of genetically modified animals.

PMID- 18629153
TI  - Functional genomics in chickens: development of integrated-systems microarrays
      for transcriptional profiling and discovery of regulatory pathways.
AB  - The genetic networks that govern the differentiation and growth of major tissues
      of economic importance in the chicken are largely unknown. Under a functional
      genomics project, our consortium has generated 30 609 expressed sequence tags
      (ESTs) and developed several chicken DNA microarrays, which represent the Chicken
      Metabolic/Somatic (10 K) and Neuroendocrine/Reproductive (8 K) Systems
      (http://udgenome.ags.udel.edu/cogburn/). One of the major challenges facing
      functional genomics is the development of mathematical models to reconstruct
      functional gene networks and regulatory pathways from vast volumes of microarray
      data. In initial studies with liver-specific microarrays (3.1 K), we have
      examined gene expression profiles in liver during the peri-hatch transition and
      during a strong metabolic perturbation-fasting and re-feeding-in divergently
      selected broiler chickens (fast vs. slow-growth lines). The expression of many
      genes controlling metabolic pathways is dramatically altered by these
      perturbations. Our analysis has revealed a large number of clusters of
      functionally related genes (mainly metabolic enzymes and transcription factors)
      that control major metabolic pathways. Currently, we are conducting
      transcriptional profiling studies of multiple tissues during development of two
      sets of divergently selected broiler chickens (fast vs. slow growing and fat vs.
      lean lines). Transcriptional profiling across multiple tissues should permit
      construction of a detailed genetic blueprint that illustrates the developmental
      events and hierarchy of genes that govern growth and development of chickens.
      This review will briefly describe the recent acquisition of chicken genomic
      resources (ESTs and microarrays) and our consortium's efforts to help launch the
      new era of functional genomics in the chicken.

PMID- 18629154
TI  - Shotgun cloning of transposon insertions in the genome of Caenorhabditis elegans.
AB  - We present a strategy to identify and map large numbers of transposon insertions
      in the genome of Caenorhabditis elegans. Our approach makes use of the mutator
      strain mut-7, which has germline-transposition activity of the Tc1/mariner family
      of transposons, a display protocol to detect new transposon insertions, and the
      availability of the genomic sequence of C. elegans. From a pilot insertional
      mutagenesis screen, we have obtained 351 new Tc1 transposons inserted in or near
      219 predicted C. elegans genes. The strategy presented provides an approach to
      isolate insertions of natural transposable elements in many C. elegans genes and
      to create a large-scale collection of C. elegans mutants.

PMID- 18629155
TI  - Antarctic genomics.
AB  - With the development of genomic science and its battery of technologies, polar
      biology stands on the threshold of a revolution, one that will enable the
      investigation of important questions of unprecedented scope and with
      extraordinary depth and precision. The exotic organisms of polar ecosystems are
      ideal candidates for genomic analysis. Through such analyses, it will be possible
      to learn not only the novel features that enable polar organisms to survive, and
      indeed thrive, in their extreme environments, but also fundamental biological
      principles that are common to most, if not all, organisms. This article aims to
      review recent developments in Antarctic genomics and to demonstrate the global
      context of such studies.

PMID- 18629157
TI  - New computational tools for brassica genome research.
AB  - With the increasing quantities of Brassica genomic data being entered into the
      public domain and in preparation for the complete Brassica genome sequencing
      effort, there is a growing requirement for the structuring and detailed
      bioinformatic analysis of Brassica genomic information within a user-friendly
      database. At the Plant Biotechnology Centre, Melbourne, Australia, we have
      developed a series of tools and computational pipelines to assist in the
      processing and structuring of genomic data, to aid its application to
      agricultural biotechnology research. These tools include a sequence database,
      ASTRA, a sequence processing pipeline incorporating annotation against GenBank,
      SwissProt and Arabidopsis Gene Ontology (GO) data and tools for molecular marker
      discovery and comparative genome analysis. All sequences are mined for simple
      sequence repeat (SSR) molecular markers using 'SSR primer' and mapped onto the
      complete Arabidopsis thaliana genome by sequence comparison. The database may be
      queried using a text-based search of sequence annotation or GO terms, BLAST
      comparison against resident sequences, or by the position of candidate
      orthologues within the Arabidopsis genome. Tools have also been developed and
      applied to the discovery of single nucleotide polymorphism (SNP) molecular
      markers and the in silico mapping of Brassica BAC end sequences onto the
      Arabidopsis genome. Planned extensions to this resource include the integration
      of gene expression data and the development of an EnsEMBL-based genome viewer.

PMID- 18629158
TI  - RNAi for plant functional genomics.
AB  - A major challenge in the post-genome era of plant biology is to determine the
      functions of all the genes in the plant genome. A straightforward approach to
      this problem is to reduce or knock out expression of a gene with the hope of
      seeing a phenotype that is suggestive of its function. Insertional mutagenesis is
      a useful tool for this type of study, but it is limited by gene redundancy,
      lethal knock-outs, nontagged mutants and the inability to target the inserted
      element to a specific gene. RNA interference (RNAi) of plant genes, using
      constructs encoding self-complementary 'hairpin' RNA, largely overcomes these
      problems. RNAi has been used very effectively in Caenorhabditis elegans
      functional genomics, and resources are currently being developed for the
      application of RNAi to high-throughput plant functional genomics.

PMID- 18629159
TI  - MAGIC database and interfaces: an integrated package for gene discovery and
      expression.
AB  - The rapidly increasing rate at which biological data is being produced requires a
      corresponding growth in relational databases and associated tools that can help
      laboratories contend with that data. With this need in mind, we describe here a
      Modular Approach to a Genomic, Integrated and Comprehensive (MAGIC) Database.
      This Oracle 9i database derives from an initial focus in our laboratory on gene
      discovery via production and analysis of expressed sequence tags (ESTs), and
      subsequently on gene expression as assessed by both EST clustering and
      microarrays. The MAGIC Gene Discovery portion of the database focuses on
      information derived from DNA sequences and on its biological relevance. In
      addition to MAGIC SEQ-LIMS, which is designed to support activities in the
      laboratory, it contains several additional subschemas. The latter include MAGIC
      Admin for database administration, MAGIC Sequence for sequence processing as well
      as sequence and clone attributes, MAGIC Cluster for the results of EST
      clustering, MAGIC Polymorphism in support of microsatellite and single-nucleotide
      polymorphism discovery, and MAGIC Annotation for electronic annotation by BLAST
      and BLAT. The MAGIC Microarray portion is a MIAME-compliant database with two
      components at present. These are MAGIC Array-LIMS, which makes possible remote
      entry of all information into the database, and MAGIC Array Analysis, which
      provides data mining and visualization. Because all aspects of interaction with
      the MAGIC Database are via a web browser, it is ideally suited not only for
      individual research laboratories but also for core facilities that serve clients
      at any distance.

PMID- 18629160
TI  - On the tetraploid origin of the maize genome.
AB  - Data from cytological and genetic mapping studies suggest that maize arose as a
      tetraploid. Two previous studies investigating the most likely mode of maize
      origin arrived at different conclusions. Gaut and Doebley proposed a segmental
      allotetraploid origin of the maize genome and estimated that the two maize
      progenitors diverged at 20.5 million years ago (mya). In a similar study, using
      larger data set, Brendel and colleagues suggested a single genome duplication at
      16 mya. One of the key components of such analyses is to examine sequence
      divergence among strictly orthologous genes. In order to identify such genes, Lai
      and colleagues sequenced five duplicated chromosomal regions from the maize
      genome and the orthologous counterparts from the sorghum genome. They also
      identified the orthologous regions in rice. Using positional information of
      genetic components, they identified 11 orthologous genes across the two
      duplicated regions of maize, and the sorghum and rice regions. Swigonova et al.
      analyzed the 11 orthologues, and showed that all five maize chromosomal regions
      duplicated at the same time, supporting a tetraploid origin of maize, and that
      the two maize progenitors diverged from each other at about the same time as each
      of them diverged from sorghum, about 11.9 mya.

PMID- 18629161
TI  - Quantitative genome-wide analysis of yeast deletion strain sensitivities to
      oxidative and chemical stress.
AB  - Understanding the actions of drugs and toxins in a cell is of critical importance
      to medicine, yet many of the molecular events involved in chemical resistance are
      relatively uncharacterized. In order to identify the cellular processes and
      pathways targeted by chemicals, we took advantage of the haploid Saccharomyces
      cerevisiae deletion strains (Winzeler et al., 1999). Although ~4800 of the
      strains are viable, the loss of a gene in a pathway affected by a drug can lead
      to a synthetic lethal effect in which the combination of a deletion and a
      normally sublethal dose of a chemical results in loss of viability. WE carried
      out genome-wide screens to determine quantitative sensitivities of the deletion
      set to four chemicals: hydrogen peroxide, menadione, ibuprofen and mefloquine.
      Hydrogen peroxide and menadione induce oxidative stress in the cell, whereas
      ibuprofen and mefloquine are toxic to yeast by unknown mechanisms. Here we report
      the sensitivities of 659 deletion strains that are sensitive to one or more of
      these four compounds, including 163 multichemicalsensitive strains, 394 strains
      specific to hydrogen peroxide and/or menadione, 47 specific to ibuprofen and 55
      specific to mefloquine.We correlate these results with data from other large
      scale studies to yield novel insights into cellular function.

PMID- 18629162
TI  - Solanaceae--a model for linking genomics with biodiversity.
AB  - Recent progress in understanding the phylogeny of the economically important
      plant family Solanaceae makes this an ideal time to develop models for linking
      the new data on plant genomics with the huge diversity of naturally occurring
      species in the family. Phylogenetics provides the framework with which to
      investigate these linkages but, critically, good species-level descriptive
      resources for the Solanaceae community are currently missing. Phylogeny in the
      family as a whole is briefly reviewed, and the new NSF Planetary Biodiversity
      Inventories project 'PBI: Solanum-a worldwide treatment' is described. The aims
      of this project are to provide species-level information across the global scope
      of the genus Solanum and to make this available over the Internet. The project is
      in its infancy, but will make available nomenclatural information, descriptions,
      keys and illustrative material for all of the approximately 1500 species of
      Solanum. With this project, the opportunity of linking valid, up-to-date
      taxonomic information about wild species of Solanum with the genomic information
      being generated about the economically important species of the genus (potato,
      tomato and eggplant) can be realized. The phylogenetic framework in which the PBI
      project is set is also of enormous potential benefit to other workers on Solanum.
      The community of biologists working with Solanaceae has a unique opportunity to
      effectively link genomics and taxonomy for better understanding of this important
      family, taking plant biology to a new level for the next century.

PMID- 18629164
TI  - Mapping the gene ontology into the unified medical language system.
AB  - We have recently mapped the Gene Ontology (GO), developed by the Gene Ontology
      Consortium, into the National Library of Medicine's Unified Medical Language
      System (UMLS). GO has been developed for the purpose of annotating gene products
      in genome databases, and the UMLS has been developed as a framework for
      integrating large numbers of disparate terminologies, primarily for the purpose
      of providing better access to biomedical information sources. The mapping of GO
      to UMLS highlighted issues in both terminology systems. After some initial
      explorations and discussions between the UMLS and GO teams, the GO was integrated
      with the UMLS. Overall, a total of 23% of the GO terms either matched directly
      (3%) or linked (20%) to existing UMLS concepts. All GO terms now have a
      corresponding, official UMLS concept, and the entire vocabulary is available
      through the web-based UMLS Knowledge Source Server. The mapping of the Gene
      Ontology, with its focus on structures, processes and functions at the molecular
      level, to the existing broad coverage UMLS should contribute to linking the
      language and practices of clinical medicine to the language and practices of
      genomics.

PMID- 18629165
TI  - Comparative genomic assessment of novel broad-spectrum targets for antibacterial
      drugs.
AB  - Single and multiple resistance to antibacterial drugs currently in use is
      spreading, since they act against only a very small number of molecular targets;
      finding novel targets for anti-infectives is therefore of great importance. All
      protein sequences from three pathogens (Staphylococcus aureus, Mycobacterium
      tuberculosis and Escherichia coli O157:H7 EDL993) were assessed via comparative
      genomics methods for their suitability as antibacterial targets according to a
      number of criteria, including the essentiality of the protein, its level of
      sequence conservation, and its distribution in pathogens, bacteria and eukaryotes
      (especially humans). Each protein was scored and ranked based on weighted
      variants of these criteria in order to prioritize proteins as potential novel
      broad-spectrum targets for antibacterial drugs. A number of proteins proved to
      score highly in all three species and were robust to variations in the scoring
      system used. Sensitivity analysis indicated the quantitative contribution of each
      metric to the overall score. After further analysis of these targets, tRNA
      methyltransferase (trmD) and translation initiation factor IF-1 (infA) emerged as
      potential and novel antimicrobial targets very worthy of further investigation.
      The scoring strategy used might be of value in other areas of post-genomic drug
      discovery.

PMID- 18629167
TI  - Design, implementation and maintenance of a model organism database for
      Arabidopsis thaliana.
AB  - The Arabidopsis Information Resource (TAIR) is a web-based community database for
      the model plant Arabidopsis thaliana. It provides an integrated view of genes,
      sequences, proteins, germplasms, clones, metabolic pathways, gene expression,
      ecotypes, polymorphisms, publications, maps and community information. TAIR is
      developed and maintained by collaboration between software developers and
      biologists. Biologists provide specification and use cases for the system,
      acquire, analyse and curate data, interact with users and test the software.
      Software developers design, implement and test the database and software. In this
      review, we briefly describe how TAIR was built and is being maintained.

PMID- 18629168
TI  - Evolution and cellular function of monothiol glutaredoxins: involvement in iron
      sulphur cluster assembly.
AB  - A number of bacterial species, mostly proteobacteria, possess monothiol
      glutaredoxins homologous to the Saccharomyces cerevisiae mitochondrial protein
      Grx5, which is involved in iron-sulphur cluster synthesis. Phylogenetic profiling
      is used to predict that bacterial monothiol glutaredoxins also participate in the
      iron-sulphur cluster (ISC) assembly machinery, because their phylogenetic
      profiles are similar to the profiles of the bacterial homologues of yeast ISC
      proteins. High evolutionary co-occurrence is observed between the Grx5 homologues
      and the homologues of the Yah1 ferredoxin, the scaffold proteins Isa1 and Isa2,
      the frataxin protein Yfh1 and the Nfu1 protein. This suggests that a specific
      functional interaction exists between these ISC machinery proteins. Physical
      interaction analyses using low-definition protein docking predict the formation
      of strong and specific complexes between Grx5 and several components of the yeast
      ISC machinery. Two-hybrid analysis has confirmed the in vivo interaction between
      Grx5 and Isa1. Sequence comparison techniques and cladistics indicate that the
      other two monothiol glutaredoxins of S. cerevisiae, Grx3 and Grx4, have evolved
      from the fusion of a thioredoxin gene with a monothiol glutaredoxin gene early in
      the eukaryotic lineage, leading to differential functional specialization. While
      bacteria do not contain these chimaeric glutaredoxins, in many eukaryotic species
      Grx5 and Grx3/4-type monothiol glutaredoxins coexist in the cell.

PMID- 18629169
TI  - Investigation into the use of C- and N-terminal GFP fusion proteins for
      subcellular localization studies using reverse transfection microarrays.
AB  - Reverse transfection microarrays were described recently as a high throughput
      method for studying gene function. We have investigated the use of this
      technology for determining the subcellular localization of proteins. Genes
      encoding 16 proteins with a variety of functions were placed in Gateway
      expression constructs with 3' or 5' green fluorescent protein (GFP) tags. These
      were then packaged in transfection reagent and spotted robotically onto a glass
      slide to form a reverse transfection array. HEK293T cells were grown over the
      surface of the array until confluent and GFP fluorescence visualized by confocal
      microscopy. All C-terminal fusion proteins localized to cellular compartments in
      accordance with previous studies and/or bioinformatic predictions. However, less
      than half of the N-terminal fusion proteins localized correctly. Of those that
      were not in concordance with the C-terminal tagged proteins, half did not exhibit
      expression and the remainder had differing subcellular localizations to the C
      terminal fusion protein. This data indicates that N-terminal tagging with GFP
      adversely affects the protein localization in reverse transfection assays,
      whereas tagging with GFP at the C-terminal is generally better in preserving the
      localization of the native protein. We discuss these results in the context of
      developing high-throughput subcellular localization assays based on the reverse
      transfection array technology.

PMID- 18629171
TI  - Comparative analysis of the testis and ovary transcriptomes in zebrafish by
      combining experimental and computational tools.
AB  - Studies on the zebrafish model have contributed to our understanding of several
      important developmental processes, especially those that can be easily studied in
      the embryo. However, our knowledge on late events such as gonad differentiation
      in the zebrafish is still limited. Here we provide an analysis on the gene sets
      expressed in the adult zebrafish testis and ovary in an attempt to identify genes
      with potential role in (zebra)fish gonad development and function. We produced
      10,533 expressed sequence tags (ESTs) from zebrafish testis or ovary and
      downloaded an additional 23,642 gonad-derived sequences from the zebrafish EST
      database. We clustered these sequences together with over 13,000 kidney-derived
      zebrafish ESTs to study partial transcriptomes for these three organs. We
      searched for genes with gonad-specific expression by screening macroarrays
      containing at least 2600 unique cDNA inserts with testis-, ovary- and kidney
      derived cDNA probes. Clones hybridizing to only one of the two gonad probes were
      selected, and subsequently screened with computational tools to identify 72 genes
      with potentially testis-specific and 97 genes with potentially ovary-specific
      expression, respectively. PCR-amplification confirmed gonad-specificity for 21 of
      the 45 clones tested (all without known function). Our study, which involves over
      47,000 EST sequences and specialized cDNA arrays, is the first analysis of adult
      organ transcriptomes of zebrafish at such a scale. The study of genes expressed
      in adult zebrafish testis and ovary will provide useful information on regulation
      of gene expression in teleost gonads and might also contribute to our
      understanding of the development and differentiation of reproductive organs in
      vertebrates.

PMID- 18629172
TI  - A case study on choosing normalization methods and test statistics for two
      channel microarray data.
AB  - DNA microarray analysis is a biological technology which permits the whole genome
      to be monitored simultaneously on a single slide. Microarray technology not only
      opens an exciting research area for biologists, but also provides significant new
      challenges to statisticians. Two very common questions in the analysis of
      microarray data are, first, should we normalize arrays to remove potential
      systematic biases, and if so, what normalization method should we use? Second,
      how should we then implement tests of statistical significance? Straightforward
      and uniform answers to these questions remain elusive. In this paper, we use a
      real data example to illustrate a practical approach to addressing these
      questions. Our data is taken from a DNA-protein binding microarray experiment
      aimed at furthering our understanding of transcription regulation mechanisms, one
      of the most important issues in biology. For the purpose of preprocessing data,
      we suggest looking at descriptive plots first to decide whether we need
      preliminary normalization and, if so, how this should be accomplished. For
      subsequent comparative inference, we recommend use of an empirical Bayes method
      (the B statistic), since it performs much better than traditional methods, such
      as the sample mean (M statistic) and Student's t statistic, and it is also
      relatively easy to compute and explain compared to the others. The false
      discovery rate (FDR) is used to evaluate the different methods, and our
      comparative results lend support to our above suggestions.

PMID- 18629174
TI  - Genome-wide analysis of the effects of heat shock on a Saccharomyces cerevisiae
      mutant with a constitutively activated cAMP-dependent pathway.
AB  - We have used DNA microarray technology and 2-D gel electrophoresis combined with
      mass spectrometry to investigate the effects of a drastic heat shock from 30 to
      50 on a genome-wide scale. This experimental condition is used to differentiate
      between wild-type cells and those with a constitutively active cAMP-dependent
      pathway in Saccharomyces cerevisiae. Whilst more than 50% of the former survive
      this shock, almost all of the latter lose viability. We compared the
      transcriptomes of the wildtype and a mutant strain deleted for the gene PDE2,
      encoding the high-affinity cAMP phosphodiesterase before and after heat shock
      treatment. We also compared the two heat-shocked samples with one another,
      allowing us to determine the changes that occur in the pde2Delta mutant which
      cause such a dramatic loss of viability after heat shock. Several genes involved
      in ergosterol biosynthesis and carbon source utilization had altered expression
      levels, suggesting that these processes might be potential factors in heat shock
      survival. These predictions and also the effect of the different phases of the
      cell cycle were confirmed by biochemical and phenotypic analyses. 146 genes of
      previously unknown function were identified amongst the genes with altered
      expression levels and deletion mutants in 13 of these genes were found to be
      highly sensitive to heat shock. Differences in response to heat shock were also
      observed at the level of the proteome, with a higher level of protein degradation
      in the mutant, as revealed by comparing 2-D gels of wild-type and mutant heat
      shocked samples and mass spectrometry analysis of the differentially produced
      proteins.

PMID- 18629175
TI  - A critical and integrated view of the yeast interactome.
AB  - Global studies of protein-protein interactions are crucial to both elucidating
      gene function and producing an integrated view of the workings of living cells.
      High-throughput studies of the yeast interactome have been performed using both
      genetic and biochemical screens. Despite their size, the overlap between these
      experimental datasets is very limited. This could be due to each approach
      sampling only a small fraction of the total interactome. Alternatively, a large
      proportion of the data from these screens may represent false-positive
      interactions. We have used the Genome Information Management System (GIMS) to
      integrate interactome datasets with transcriptome and protein annotation data and
      have found significant evidence that the proportion of false-positive results is
      high. Not all high-throughput datasets are similarly contaminated, and the tandem
      affinity purification (TAP) approach appears to yield a high proportion of
      reliable interactions for which corroborating evidence is available. From our
      integrative analyses, we have generated a set of verified interactome data for
      yeast.

PMID- 18629176
TI  - Som-based class discovery exploring the ICA-reduced features of microarray
      expression profiles.
AB  - Gene expression datasets are large and complex, having many variables and unknown
      internal structure. We apply independent component analysis (ICA) to derive a
      less redundant representation of the expression data. The decomposition produces
      components with minimal statistical dependence and reveals biologically relevant
      information. Consequently, to the transformed data, we apply cluster analysis (an
      important and popular analysis tool for obtaining an initial understanding of the
      data, usually employed for class discovery). The proposed self-organizing map
      (SOM)-based clustering algorithm automatically determines the number of 'natural'
      subgroups of the data, being aided at this task by the available prior knowledge
      of the functional categories of genes. An entropy criterion allows each gene to
      be assigned to multiple classes, which is closer to the biological
      representation. These features, however, are not achieved at the cost of the
      simplicity of the algorithm, since the map grows on a simple grid structure and
      the learning algorithm remains equal to Kohonen's one.

PMID- 18629178
TI  - Overview and utilization of the NCI thesaurus.
AB  - The NCI Thesaurus is a reference terminology covering areas of basic and clinical
      science, built with the goal of facilitating translational research in cancer. It
      contains nearly 110 000 terms in approximately 36000 concepts, partitioned in 20
      subdomains, which include diseases, drugs, anatomy, genes, gene products,
      techniques, and biological processes, among others, all with a cancer-centric
      focus in content, and originally designed to support coding activities across the
      National Cancer Institute. Each concept represents a unit of meaning and contains
      a number of annotations, such as synonyms and preferred name, as well as
      annotations such as textual definitions and optional references to external
      authorities. In addition, concepts are modelled with description logic (DL) and
      defined by their relationships to other concepts; there are currently
      approximately 90 types of named relations declared in the terminology. The NCI
      Thesaurus is produced by the Enterprise Vocabulary Services project, a
      collaborative effort between the NCI Center for Bioinformatics and the NCI Office
      of Communications, and is part of the caCORE infrastructure stack
      (http://ncicb.nci.nih.gov/NCICB/core). It can be accessed programmatically
      through the open caBIO API and browsed via the web (http://nciterms.nci.nih.gov).
      A history of editing changes is also accessible through the API. In addition, the
      Thesaurus is available for download in various file formats, including OWL, the
      web ontology language, to facilitate its utilization by others.

PMID- 18629179
TI  - Sequence ontology annotation guide.
AB  - This Sequence Ontology (SO) [13] aims to unify the way in which we describe
      sequence annotations, by providing a controlled vocabulary of terms and the
      relationships between them. Using SO terms to label the parts of sequence
      annotations greatly facilitates downstream analyses of their contents, as it
      ensures that annotations produced by different groups conform to a single
      standard. This greatly facilitates analyses of annotation contents and
      characteristics, e.g. comparisons of UTRs, alternative splicing, etc. Because SO
      also specifies the relationships between features, e.g. part_of, kind_of,
      annotations described with SO terms are also better substrates for validation and
      visualization software.This document provides a step-by-step guide to producing a
      SO compliant file describing a sequence annotation. We illustrate this by using
      an annotated gene as an example. First we show where the terms needed to describe
      the gene's features are located in SO and their relationships to one another. We
      then show line by line how to format the file to construct a SO compliant
      annotation of this gene.

PMID- 18629180
TI  - Exploring the foundation of genomics: a northern blot reference set for the
      comparative analysis of transcript profiling technologies.
AB  - In this paper we aim to create a reference data collection of Northern blot
      results and demonstrate how such a collection can enable a quantitative
      comparison of modern expression profiling techniques, a central component of
      functional genomics studies. Historically, Northern blots were the de facto
      standard for determining RNA transcript levels. However, driven by the demand for
      analysis of large sets of genes in parallel, high-throughput methods, such as
      microarrays, dominate modern profiling efforts. To facilitate assessment of these
      methods, in comparison to Northern blots, we created a database of published
      Northern results obtained with a standardized commercial multiple tissue blot
      (dbMTN). In order to demonstrate the utility of the dbMTN collection for
      technology comparison, we also generated expression profiles for genes across a
      set of human tissues, using multiple profiling techniques. No method produced
      profiles that were strongly correlated with the Northern blot data. The highest
      correlations to the Northern blot data were determined with microarrays for the
      subset of genes observed to be specifically expressed in a single tissue in the
      Northern analyses. The database and expression profiling data are available via
      the project website (http://www.cisreg.ca). We believe that emphasis on
      multitechnique validation of expression profiles is justified, as the correlation
      results between platforms are not encouraging on the whole. Supplementary
      material for this article can be found at:
      http://www.interscience.wiley.com/jpages/1531-6912/suppmat.

PMID- 18629181
TI  - Maternally and paternally silenced imprinted genes differ in their intron
      content.
AB  - Imprinted genes exhibit silencing of one of the parental alleles during embryonic
      development. In a previous study imprinted genes were found to have reduced
      intron content relative to a non-imprinted control set (Hurst et al., 1996).
      However, due to the small sample size, it was not possible to analyse the source
      of this effect. Here, we re-investigate this observation using larger datasets of
      imprinted and control (non-imprinted) genes that allow us to consider mouse and
      human, and maternally and paternally silenced, imprinted genes separately. We
      find that, in the human and mouse, there is reduced intron content in the
      maternally silenced imprinted genes relative to a non-imprinted control set.
      Among imprinted genes, a strong bias is also observed in the distribution of
      intronless genes, which are found exclusively in the maternally silenced dataset.
      The paternally silenced dataset in the human is not different to the control set;
      however, the mouse paternally silenced dataset has more introns than the control
      group. A direct comparison of mouse maternally and paternally silenced imprinted
      gene datasets shows that they differ significantly with respect to a variety of
      intron-related parameters. We discuss a variety of possible explanations for our
      observations.

PMID- 18629182
TI  - A special section of reviews from the 2 conference on Standards and Ontologies
      for Functional Genomics (SOFG).

PMID- 18629184
TI  - Standardization Initiatives in the (eco)toxicogenomics domain: a review.
AB  - The purpose of this document is to provide readers with a resource of different
      ongoing standardization efforts within the 'omics' (genomic, proteomics,
      metabolomics) and related communities, with particular focus on toxicological and
      environmental applications. The review includes initiatives within the research
      community as well as in the regulatory arena. It addresses data management issues
      (format and reporting structures for the exchange of information) and database
      interoperability, highlighting key objectives, target audience and participants.
      A considerable amount of work still needs to be done and, ideally, collaboration
      should be optimized and duplication and incompatibility should be avoided where
      possible. The consequence of failing to deliver data standards is an escalation
      in the burden and cost of data management tasks.

PMID- 18629185
TI  - Standards and ontologies for functional genomics 2.

PMID- 18629186
TI  - The Montagues and the Capulets.
AB  - Two households, both alike in dignity, In fair Genomics, where we lay our scene,
      (One, comforted by its logic's rigour, Claims ontology for the realm of pure, The
      other, with blessed scientist's vigour, Acts hastily on models that endure), From
      ancient grudge break to new mutiny, When 'being' drives a fly-man to blaspheme.
      From forth the fatal loins of these two foes, Researchers to unlock the book of
      life; Whole misadventured piteous overthrows, Can with their work bury their
      clans' strife. The fruitful passage of their GO-mark'd love, And the continuance
      of their studies sage, Which, united, yield ontologies undreamed-of, Is now the
      hour's traffic of our stage; The which if you with patient ears attend, What here
      shall miss, our toil shall strive to mend.

PMID- 18629188
TI  - Xenogenomics: genomic bioprospecting in indigenous and exotic plants through EST
      discovery, cDNA microarray-based expression profiling and functional genomics.
AB  - To date, the overwhelming majority of genomics programs in plants have been
      directed at model or crop plant species, meaning that very little of the
      naturally occurring sequence diversity found in plants is available for
      characterization and exploitation. In contrast, 'xenogenomics' refers to the
      discovery and functional analysis of novel genes and alleles from indigenous and
      exotic species, permitting bioprospecting of biodiversity using high-throughput
      genomics experimental approaches. Such a program has been initiated to
      bioprospect for genetic determinants of abiotic stress tolerance in indigenous
      Australian flora and native Antarctic plants. Uniquely adapted Poaceae and
      Fabaceae species with enhanced tolerance to salt, drought, elevated soil
      aluminium concentration, and freezing stress have been identified, based
      primarily on their eco-physiology, and have been subjected to structural and
      functional genomics analyses. For each species, EST collections have been derived
      from plants subjected to appropriate abiotic stresses. Transcript profiling with
      spotted unigene cDNA micro-arrays has been used to identify genes that are
      transcriptionally modulated in response to abiotic stress. Candidate genes
      identified on the basis of sequence annotation or transcript profiling have been
      assayed in planta and other in vivo systems for their capacity to confer novel
      phenotypes. Comparative genomics analysis of novel genes and alleles identified
      in the xenogenomics target plant species has subsequently been undertaken with
      reference to key model and crop plants.

PMID- 18629187
TI  - Swine Genome Sequencing Consortium (SGSC): a strategic roadmap for sequencing the
      pig genome.
AB  - The Swine Genome Sequencing Consortium (SGSC) was formed in September 2003 by
      academic, government and industry representatives to provide international
      coordination for sequencing the pig genome. The SGSC's mission is to advance
      biomedical research for animal production and health by the development of
      DNAbased tools and products resulting from the sequencing of the swine genome.
      During the past 2 years, the SGSC has met bi-annually to develop a strategic
      roadmap for creating the required scientific resources, to integrate existing
      physical maps, and to create a sequencing strategy that captured international
      participation and a broad funding base. During the past year, SGSC members have
      integrated their respective physical mapping data with the goal of creating a
      minimal tiling path (MTP) that will be used as the sequencing template. During
      the recent Plant and Animal Genome meeting (January 16, 2005 San Diego, CA),
      presentations demonstrated that a human-pig comparative map has been completed,
      BAC fingerprint contigs (FPC) for each of the autosomes and X chromosome have
      been constructed and that BAC end-sequencing has permitted, through BLAST
      analysis and RH-mapping, anchoring of the contigs. Thus, significant progress has
      been made towards the creation of a MTP. In addition, whole-genome (WG) shotgun
      libraries have been constructed and are currently being sequenced in various
      laboratories around the globe. Thus, a hybrid sequencing approach in which 3x
      coverage of BACs comprising the MTP and 3x of the WG-shotgun libraries will be
      used to develop a draft 6x coverage of the pig genome.

PMID- 18629190
TI  - Effect of stress on viral-bacterial synergy in bovine respiratory disease: novel
      mechanisms to regulate inflammation.
AB  - The severity of bovine respiratory infections has been linked to a variety of
      factors, including environmental and nutritional changes, transportation, and
      social reorganization of weaned calves. Fatal respiratory infections, however,
      usually occur when a primary viral infection compromises host defences and
      enhances the severity of a secondary bacterial infection. This viral-bacterial
      synergy can occur by a number of different mechanisms and disease challenge
      models have been developed to analyse host responses during these respiratory
      infections. A primary bovine herpesvirus-1 (BHV-1) respiratory infection followed
      by a secondary challenge with Mannheimia haemolytica results in fatal bovine
      respiratory disease (BRD) and host responses to these two pathogens have been
      studied extensively. We used this disease model to demonstrate that stress
      significantly altered the viral-bacterial synergy resulting in fatal BRD.
      Functional genomic analysis revealed that BHV-1 infection enhanced toll-like
      receptors (TLR) expression and increased pro-inflammatory responses which
      contribute to the severity of a Mannheimia haemolytica infection. TLRs play a
      critical role in detecting bacterial infections and inducing pro-inflammatory
      responses. It is difficult to understand, however, how stress-induced
      corticosteroids could enhance this form of viral-bacterial synergy. Nuclear
      translocation of the glucocorticoid receptor activates cell signalling pathways
      which inhibit both TLR signalling and pro-inflammatory responses. The apparent
      conundrum between stress-induced corticosteroids and enhanced BRD susceptibility
      is discussed in terms of present data and previous investigations of stress and
      respiratory disease.

PMID- 18629191
TI  - Proteomic analysis of colorectal cancer: prefractionation strategies using two
      dimensional free-flow electrophoresis.
AB  - This review deals with the application of a new prefractionation tool, free-flow
      electrophoresis (FFE), for proteomic analysis of colorectal cancer (CRC). CRC is
      a leading cause of cancer death in the Western world. Early detection is the
      single most important factor influencing outcome of CRC patients. If identified
      while the disease is still localized, CRC is treatable. To improve outcomes for
      CRC patients there is a pressing need to identify biomarkers for early detection
      (diagnostic markers), prognosis (prognostic indicators), tumour responses
      (predictive markers) and disease recurrence (monitoring markers). Despite recent
      advances in the use of genomic analysis for risk assessment, in the area of
      biomarker identification genomic methods alone have yet to produce reliable
      candidate markers for CRC. For this reason, attention is being directed towards
      proteomics as a complementary analytical tool for biomarker identification. Here
      we describe a proteomics separation tool, which uses a combination of continuous
      FFE, a liquid-based isoelectric focusing technique, in the first dimension,
      followed by rapid reversed-phase HPLC (1-6 min/analysis) in the second dimension.
      We have optimized imaging software to present the FFE/RP-HPLC data in a virtual
      2D gel-like format. The advantage of this liquid based fractionation system over
      traditional gel-based fractionation systems is the ability to fractionate large
      quantity protein samples. Unlike 2D gels, the method is applicable to both high
      M(r) proteins and small peptides, which are difficult to separate, and in the
      case of peptides, are not retained in standard 2D gels.

PMID- 18629192
TI  - A 4 Mb high resolution BAC contig on bovine chromosome 1q12 and comparative
      analysis with human chromosome 21q22.
AB  - The bovine RPCI-42 BAC library was screened to construct a sequence-ready ~4 Mb
      single contig of 92 BAC clones on BTA 1q12. The contig covers the region between
      the genes KRTAP8P1 and CLIC6. This genomic segment in cattle is of special
      interest as it contains the dominant gene responsible for the hornless or polled
      phenotype in cattle. The construction of the BAC contig was initiated by
      screening the bovine BAC library with heterologous cDNA probes derived from 12
      human genes of the syntenic region on HSA 21q22. Contig building was facilitated
      by BAC end sequencing and chromosome walking. During the construction of the
      contig, 165 BAC end sequences and 109 single-copy STS markers were generated. For
      comparative mapping of 25 HSA 21q22 genes, genomic PCR primers were designed from
      bovine EST sequences and the gene-associated STSs mapped on the contig.
      Furthermore, bovine BAC end sequence comparisons against the human genome
      sequence revealed significant matches to HSA 21q22 and allowed the in silico
      mapping of two new genes in cattle. In total, 31 orthologues of human genes
      located on HSA 21q22 were directly mapped within the bovine BAC contig, of which
      16 genes have been cloned and mapped for the first time in cattle. In contrast to
      the existing comparative bovine-human RH maps of this region, these results
      provide a better alignment and reveal a completely conserved gene order in this 4
      Mb segment between cattle, human and mouse. The mapping of known polled linked
      BTA 1q12 microsatellite markers allowed the integration of the physical contig
      map with existing linkage maps of this region and also determined the exact order
      of these markers for the first time. Our physical map and transcript map may be
      useful for positional cloning of the putative polled gene in cattle.

PMID- 18629193
TI  - The cadherin superfamily in Anopheles gambiae: a comparative study with
      Drosophila melanogaster.
AB  - The cadherin superfamily is a diverse and multifunctional group of proteins with
      extensive representation across genomes of phylogenetically distant species that
      is involved in cell-cell communication and adhesion. The mosquito Anopheles
      gambiae is an emerging model organism for the study of innate immunity and host
      pathogen interactions, where the malaria parasite induces a profound
      rearrangement of the actin cytoskeleton at critical stages of infection. We have
      used bioinformatics tools to retrieve present sequence knowledge about the
      complete repertoire of cadherins in A. gambiae and compared it to that of the
      fruit fly, Drosophila melanogaster. In A. gambiae, we have identified 43 genes
      coding for cadherin extracellular domains that were re-annotated to 38 genes and
      represent an expansion of this gene family in comparison to other invertebrate
      organisms. The majority of Drosophila cadherins show a 1 : 1 Anopheles
      orthologue, but we have observed a remarkable expansion in some groups in A.
      gambiae, such as N-cadherins, that were recently shown to have a role in the
      olfactory system of the fruit fly. In vivo dsRNA silencing of overrepresented
      genes in A. gambiae and other genes showing expression at critical tissues for
      parasite infection will likely advance our understanding of the problems of host
      preference and hostpathogen interactions in this mosquito species.

PMID- 18629194
TI  - A phylogenomic study of the genus Alphavirus employing whole genome comparison.
AB  - The phylogenetics of the genus Alphavirus have historically been characterized
      using partial gene, single gene or partial proteomic data. We have mined cDNA and
      amino acid sequences from GenBank for all fully sequenced and some partially
      sequenced alphaviruses and generated phylogenomic analyses of the genus
      Alphavirus genus, employing capsid encoding structural regions, non-structural
      coding regions and complete viral genomes. Our studies support the presence of
      the previously reported recombination event that produced the Western Equine
      Encephalitis clade, and confirm many of the patterns of geographic radiation and
      divergence of the multiple species. Our data suggest that the Salmon Pancreatic
      Disease Virus and Sleeping Disease Virus are sufficiently divergent to form a
      separate clade from the other alphaviruses. Also, unlike previously reported
      studies employing limited sequence data for correlation of phylogeny, our results
      indicate that the Barmah Forest Virus and Middelburg Virus appear to be members
      of the Semliki Forest clade. Additionally, our analysis indicates that the
      Southern Elephant Seal Virus is part of the Semliki Forest clade, although still
      phylogenetically distant from all known members of the genus Alphavirus. Finally,
      we demonstrate that the whole Rubella viral genome provides an ideal outgroup for
      phylogenomic studies of the genus Alphavirus.

PMID- 18629196
TI  - The 8 annual bio-ontologies meeting.

PMID- 18629198
TI  - Towards inference of a biochemical ontology from a metabolic database.
AB  - In order to predict the metabolic fate of an arbitrary compound based solely on
      structure, it is useful to be able to identify substructural 'functional groups'
      that are biochemically reactive. These functional groups are the substructural
      elements that can be removed and replaced to transform one compound into another.
      This problem of identifying functional groups is related to the problem of
      classifying compounds. The research presented here discusses the state of the art
      in biochemical databases and how these sources may be applied to the problem of
      classifying compounds based solely on structure. We describe a biochemical
      informatics system for processing molecular data and describe how 100 255
      compositional (hasA) relationships are inferred between 835 abstractions and 9500
      metabolites from the KEGG Ligand database. Specifically, we focus on the
      identification of amino acids and consider ways in which the inference of
      biochemical ontologies for metabolites will be improved in the future.

PMID- 18629199
TI  - On carcinomas and other pathological entities.
AB  - Tumours, abscesses, cysts, scars and fractures are familiar types of what we
      shall call pathological continuant entities. The instances of such types exist
      always in or on anatomical structures, which thereby become transformed into
      pathological anatomical structures of corresponding types: a fractured tibia, a
      blistered thumb, a carcinomatous colon. In previous work on biomedical ontologies
      we showed how the provision of formal definitions for relations such as is_a,
      part_of and transformation_of can facilitate the integration of such ontologies
      in ways which have the potential to support new kinds of automated reasoning. We
      here extend this approach to the treatment of pathologies, focusing especially on
      those pathological continuant entities which arise when organs become affected by
      carcinomas.

PMID- 18629200
TI  - A special section of articles from the 8 annual bio-ontologies meeting.

PMID- 18629202
TI  - Using multiple ontologies to integrate complex biological data.
AB  - The strength of the rat as a model organism lies in its utility in pharmacology,
      biochemistry and physiology research. Data resulting from such studies is
      difficult to represent in databases and the creation of user-friendly data mining
      tools has proved difficult. The Rat Genome Database has developed a comprehensive
      ontology-based data structure and annotation system to integrate physiological
      data along with environmental and experimental factors, as well as genetic and
      genomic information. RGD uses multiple ontologies to integrate complex biological
      information from the molecular level to the whole organism, and to develop data
      mining and presentation tools. This approach allows RGD to indicate not only the
      phenotypes seen in a strain but also the specific values under each diet and
      atmospheric condition, as well as gender differences. Harnessing the power of
      ontologies in this way allows the user to gather and filter data in a customized
      fashion, so that a researcher can retrieve all phenotype readings for which a
      high hypoxia is a factor. Utilizing the same data structure for expression data,
      pathways and biological processes, RGD will provide a comprehensive research
      platform which allows users to investigate the conditions under which biological
      processes are altered and to elucidate the mechanisms of disease.

PMID- 18629203
TI  - eGenomics: genomes and the environment.

PMID- 18629206
TI  - In silico analysis for transcription factors with Zn(II)(2)C(6) binuclear cluster
      DNA-binding domains in Candida albicans.
AB  - A total of 6047 open reading frames in the Candida albicans genome were screened
      for Zn(II)(2)C(6)-type zinc cluster proteins (or binuclear cluster proteins)
      involved in DNA recognition. These fungal proteins are transcription regulators
      of genes involved in a wide range of cellular processes, including metabolism of
      different compounds such as sugars or amino acids, as well as multi-drug
      resistance, control of meiosis, cell wall architecture, etc. The selection
      criteria used in the sequence analysis were the presence of the
      CysX(2)CysX(6)CysX(5-16)CysX(2)CysX(6-8)Cys motif and a putative nuclear
      localization signal. Using this approach, 70 putative Zn(II)(2)C(6) transcription
      factors have been found in the genome of C. albicans.

PMID- 18629207
TI  - Plant Ontology (PO): a Controlled Vocabulary of Plant Structures and Growth
      Stages.
AB  - The Plant Ontology Consortium (POC) (www.plantontology.org) is a collaborative
      effort among several plant databases and experts in plant systematics, botany and
      genomics. A primary goal of the POC is to develop simple yet robust and
      extensible controlled vocabularies that accurately reflect the biology of plant
      structures and developmental stages. These provide a network of vocabularies
      linked by relationships (ontology) to facilitate queries that cut across datasets
      within a database or between multiple databases. The current version of the
      ontology integrates diverse vocabularies used to describe Arabidopsis, maize and
      rice (Oryza sp.) anatomy, morphology and growth stages. Using the ontology
      browser, over 3500 gene annotations from three species-specific databases, The
      Arabidopsis Information Resource (TAIR) for Arabidopsis, Gramene for rice and
      MaizeGDB for maize, can now be queried and retrieved.

PMID- 18629208
TI  - eGenomics: Cataloguing our Complete Genome Collection.

PMID- 18629210
TI  - ESF workshop on 'Sustainability and Governance of Web and GRID Resources in
      Functional Genomics'.

PMID- 18629212
TI  - Poultry genomics puts meat on the table.

PMID- 18629217
TI  - Atypical CTSK transcripts and ARNT transcription read-through into CTSK.
AB  - The aryl hydrocarbon receptor nuclear translocator (ARNT) and cathepsin K (CTSK)
      genes lie in a tandem head-to-tail arrangement on human chromosome 1. The two
      genes are in extremely close proximity; the usual CTSK transcription start site
      is less than 1.4 kb downstream of the end of the longest reported ARNT
      transcript. By generating an RT-PCR product that overlaps both the 3' end of ARNT
      and the 5' end of CTSK, we show that ARNT transcripts may extend through the ARNT
      CTSK intergenic region and progress into the CTSK gene. Furthermore, by using
      quantitative RT-PCR from several tissues to detect the ARNT expression signature
      in CTSK introns, we show that ARNT transcripts can read through into CTSK as far
      as CTSK intron 3, extending approximately 3.7 kb downstream of the end of the
      longest previously described ARNT mRNA. Given that ARNT and CTSK are expressed in
      an overlapping range of tissues, ARNT read-through may have a negative impact on
      CTSK transcript levels by interfering with CTSK expression. We also present
      evidence for novel CTSK transcripts following sequence analysis of CTSK-derived
      ESTs and RT-PCR products. These transcripts show alternate 5' splicing and or 5'
      extension and are sometimes initiated from a cryptic alternative promoter which
      is upstream of the known CTSK promoter and possibly in the 3' UTR of ARNT.

PMID- 18629211
TI  - Identification and comparative analysis of the peptidyl-prolyl cis/trans
      isomerase repertoires of H. sapiens, D. melanogaster, C. elegans, S. cerevisiae
      and Sz. pombe.
AB  - The peptidyl-prolyl cis/trans isomerase (PPIase) class of proteins comprises
      three member families that are found throughout nature and are present in all the
      major compartments of the cell. Their numbers appear to be linked to the number
      of genes in their respective genomes, although we have found the human repertoire
      to be smaller than expected due to a reduced cyclophilin repertoire. We show here
      that whilst the members of the cyclophilin family (which are predominantly found
      in the nucleus and cytoplasm) and the parvulin family (which are predominantly
      nuclear) are largely conserved between different repertoires, the FKBPs (which
      are predominantly found in the cytoplasm and endoplasmic reticulum) are not. It
      therefore appears that the cyclophilins and parvulins have evolved to perform
      conserved functions, while the FKBPs have evolved to fill ever-changing niches
      within the constantly evolving organisms. Many orthologous subgroups within the
      different PPIase families appear to have evolved from a distinct common ancestor,
      whereas others, such as the mitochondrial cyclophilins, appear to have evolved
      independently of one another. We have also identified a novel parvulin within
      Drosophila melanogaster that is unique to the fruit fly, indicating a recent
      evolutionary emergence. Interestingly, the fission yeast repertoire, which
      contains no unique cyclophilins and parvulins, shares no PPIases solely with the
      budding yeast but it does share a majority with the higher eukaryotes in this
      study, unlike the budding yeast. It therefore appears that, in comparison with
      Schizosaccharomyces pombe, Saccharomyces cerevisiae is a poor representation of
      the higher eukaryotes for the study of PPIases.

PMID- 18629218
TI  - Characterization of expressed sequence tags from a gallus gallus pineal gland
      cDNA library.
AB  - The pineal gland is the circadian oscillator in the chicken, regulating diverse
      functions ranging from egg laying to feeding. Here, we describe the isolation and
      characterization of expressed sequence tags (ESTs) isolated from a chicken pineal
      gland cDNA library. A total of 192 unique sequences were analysed and submitted
      to GenBank; 6% of the ESTs matched neither GenBank cDNA sequences nor the newly
      assembled chicken genomic DNA sequence, three ESTs aligned with sequences
      designated to be on the Z_random, while one matched a W chromosome sequence and
      could be useful in cataloguing functionally important genes on this sex
      chromosome. Additionally, single nucleotide polymorphisms (SNPs) were identified
      and validated in 10 ESTs that showed 98% or higher sequence similarity to known
      chicken genes. Here, we have described resources that may be useful in
      comparative and functional genomic analysis of genes expressed in an important
      organ, the pineal gland, in a model and agriculturally important organism.

PMID- 18629219
TI  - The Korea brassica genome project: a glimpse of the brassica genome based on
      comparative genome analysis with Arabidopsis.
AB  - A complete genome sequence provides unlimited information in the sequenced
      organism as well as in related taxa. According to the guidance of the
      Multinational Brassica Genome Project (MBGP), the Korea Brassica Genome Project
      (KBGP) is sequencing chromosome 1 (cytogenetically oriented chromosome #1) of
      Brassica rapa. We have selected 48 seed BACs on chromosome 1 using EST genetic
      markers and FISH analyses. Among them, 30 BAC clones have been sequenced and 18
      are on the way. Comparative genome analyses of the EST sequences and sequenced
      BAC clones from Brassica chromosome 1 revealed their homeologous partner regions
      on the Arabidopsis genome and a syntenic comparative map between Brassica
      chromosome 1 and Arabidopsis chromosomes. In silico chromosome walking and clone
      validation have been successfully applied to extending sequence contigs based on
      the comparative map and BAC end sequences. In addition, we have defined the
      (peri)centromeric heterochromatin blocks with centromeric tandem repeats, rDNA
      and centromeric retrotransposons. In-depth sequence analyses of five homeologous
      BAC clones and an Arabidopsis chromosomal region reveal overall co-linearity,
      with 82% sequence similarity. The data indicate that the Brassica genome has
      undergone triplication and subsequent gene losses after the divergence of
      Arabidopsis and Brassica. Based on in-depth comparative genome analyses, we
      propose a comparative genomics approach for conquering the Brassica genome. In
      2005 we intend to construct an integrated physical map, including sequence
      information from 500 BAC clones and integration of fingerprinting data and end
      sequence data of more than 100,000 BAC clones.

PMID- 18629220
TI  - Reassessing design and analysis of two-colour microarray experiments using mixed
      effects models.
AB  - Gene expression microarray studies have led to interesting experimental design
      and statistical analysis challenges. The comparison of expression profiles across
      populations is one of the most common objectives of microarray experiments. In
      this manuscript we review some issues regarding design and statistical analysis
      for two-colour microarray platforms using mixed linear models, with special
      attention directed towards the different hierarchical levels of replication and
      the consequent effect on the use of appropriate error terms for comparing
      experimental groups. We examine the traditional analysis of variance (ANOVA)
      models proposed for microarray data and their extensions to hierarchically
      replicated experiments. In addition, we discuss a mixed model methodology for
      power and efficiency calculations of different microarray experimental designs.

PMID- 18629221
TI  - Computational tools for Brassica-Arabidopsis comparative genomics.
AB  - Recent advances, such as the availability of extensive genome survey sequence
      (GSS) data and draft physical maps, are radically transforming the means by which
      we can dissect Brassica genome structure and systematically relate it to the
      Arabidopsis model. Hitherto, our view of the co-linearities between these closely
      related genomes had been largely inferred from comparative RFLP data,
      necessitating substantial interpolation and expert interpretation. Sequencing of
      the Brassica rapa genome by the Multinational Brassica Genome Project will,
      however, enable an entirely computational approach to this problem. Meanwhile we
      have been developing databases and bioinformatics tools to support our work in
      Brassica comparative genomics, including a recently completed draft physical map
      of B. rapa integrated with anchor probes derived from the Arabidopsis genome
      sequence. We are also exploring new ways to display the emerging Brassica
      Arabidopsis sequence homology data. We have mapped all publicly available
      Brassica sequences in silico to the Arabidopsis TIGR v5 genome sequence and
      published this in the ATIDB database that uses Generic Genome Browser (GBrowse).
      This in silico approach potentially identifies all paralogous sequences and so we
      colour-code the significance of the mappings and offer an integrated, real-time
      multiple alignment tool to partition them into paralogous groups. The MySQL
      database driving GBrowse can also be directly interrogated, using the powerful
      API offered by the Perl BioColon, two colonsDBColon, two colonsGFF methods,
      facilitating a wide range of data-mining possibilities.

PMID- 18629222
TI  - Meta-analysis combines affymetrix microarray results across laboratories.
AB  - With microarray technology becoming more prevalent in recent years, it is now
      common for several laboratories to employ the same microarray technology to
      identify differentially expressed genes that are related to the same phenomenon
      in the same species. Although experimental specifics may be similar, each
      laboratory will typically produce a slightly different list of statistically
      significant genes, which calls into question the validity of each gene list (i.e.
      which list is best). A statistically-based meta-analytic approach to microarray
      analysis systematically combines results from the different laboratories to
      provide a single estimate of the degree of differential expression for each gene.
      This approach provides a more precise view of genes that are of significant
      interest, while simultaneously allowing for differences between laboratories. The
      widely-used Affymetrix oligonucleotide array and its software are of particular
      interest because the results are naturally suited to a meta-analysis. A
      simulation model based on the Affymetrix platform is developed to examine the
      adaptive nature of the meta-analytic approach and to illustrate the utility of
      such an approach in combining microarray results across laboratories.

PMID- 18629225
TI  - Design and calibration of microarrays as universal transcriptomic environmental
      biosensors.

PMID- 18629226
TI  - The Tomato Sequencing Project, the first cornerstone of the International
      Solanaceae Project (SOL).
AB  - The genome of tomato (Solanum lycopersicum) is being sequenced by an
      international consortium of 10 countries (Korea, China, the United Kingdom,
      India, The Netherlands, France, Japan, Spain, Italy and the United States) as
      part of a larger initiative called the 'International Solanaceae Genome Project
      (SOL): Systems Approach to Diversity and Adaptation'. The goal of this grassroots
      initiative, launched in November 2003, is to establish a network of information,
      resources and scientists to ultimately tackle two of the most significant
      questions in plant biology and agriculture: (1) How can a common set of
      genes/proteins give rise to a wide range of morphologically and ecologically
      distinct organisms that occupy our planet? (2) How can a deeper understanding of
      the genetic basis of plant diversity be harnessed to better meet the needs of
      society in an environmentally friendly and sustainable manner? The Solanaceae and
      closely related species such as coffee, which are included in the scope of the
      SOL project, are ideally suited to address both of these questions. The first
      step of the SOL project is to use an ordered BAC approach to generate a high
      quality sequence for the euchromatic portions of the tomato as a reference for
      the Solanaceae. Due to the high level of macro and micro-synteny in the
      Solanaceae the BAC-by-BAC tomato sequence will form the framework for shotgun
      sequencing of other species. The starting point for sequencing the genome is BACs
      anchored to the genetic map by overgo hybridization and AFLP technology. The
      overgos are derived from approximately 1500 markers from the tomato high density
      F2-2000 genetic map (http://sgn.cornell.edu/). These seed BACs will be used as
      anchors from which to radiate the tiling path using BAC end sequence data.
      Annotation will be performed according to SOL project guidelines. All the
      information generated under the SOL umbrella will be made available in a
      comprehensive website. The information will be interlinked with the ultimate goal
      that the comparative biology of the Solanaceae-and beyond-achieves a context that
      will facilitate a systems biology approach.

PMID- 18629227
TI  - Plant reproductive genomics at the Plant and Animal Genome Conference.

PMID- 18629228
TI  - The International Cotton Genome Initiative Workshop I, at PAG XIII.

PMID- 18629229
TI  - Bovine genomics from academia to industry.

PMID- 18629236
TI  - Meeting Review: The Intelligent Systems in Bioinformatics Conference 2001
      (ISMB2001).

PMID- 18629237
TI  - How useful will functional proteomics data be?

PMID- 18629230
TI  - Metabolic control analysis: a tool for designing strategies to manipulate
      metabolic pathways.
AB  - The traditional experimental approaches used for changing the flux or the
      concentration of a particular metabolite of a metabolic pathway have been mostly
      based on the inhibition or over-expression of the presumed rate-limiting step.
      However, the attempts to manipulate a metabolic pathway by following such
      approach have proved to be unsuccessful. Metabolic Control Analysis (MCA)
      establishes how to determine, quantitatively, the degree of control that a given
      enzyme exerts on flux and on the concentration of metabolites, thus substituting
      the intuitive, qualitative concept of rate limiting step. Moreover, MCA helps to
      understand (i) the underlying mechanisms by which a given enzyme exerts high or
      low control and (ii) why the control of the pathway is shared by several pathway
      enzymes and transporters. By applying MCA it is possible to identify the steps
      that should be modified to achieve a successful alteration of flux or metabolite
      concentration in pathways of biotechnological (e.g., large scale metabolite
      production) or clinical relevance (e.g., drug therapy). The different MCA
      experimental approaches developed for the determination of the flux-control
      distribution in several pathways are described. Full understanding of the pathway
      properties when is working under a variety of conditions can help to attain a
      successful manipulation of flux and metabolite concentration.

PMID- 18629239
TI  - Extracting information automatically from biological literature.

PMID- 18629240
TI  - Identification of membrane proteins in the hyperthermophilic archaeon pyrococcus
      furiosus using proteomics and prediction programs.
AB  - Cell-free extracts from the hyperthermophilic archaeon Pyrococcus furiosus were
      separated into membrane and cytoplasmic fractions and each was analyzed by 2D-gel
      electrophoresis. A total of 66 proteins were identified, 32 in the membrane
      fraction and 34 in the cytoplasmic fraction. Six prediction programs were used to
      predict the subcellular locations of these proteins. Three were based on signal
      peptides (SignalP, TargetP, and SOSUISignal) and three on transmembrane-spanning
      alpha-helices (TSEG, SOSUI, and PRED-TMR2). A consensus of the six programs
      predicted that 23 of the 32 proteins (72%) from the membrane fraction should be
      in the membrane and that all of the proteins from the cytoplasmic fraction should
      be in the cytoplasm. Two membrane-associated proteins predicted to be cytoplasmic
      by the programs are also predicted to consist primarily of transmembrane-spanning
      beta-sheets using porin protein models, suggesting that they are, in fact,
      membrane components. An ATPase subunit homolog found in the membrane fraction,
      although predicted to be cytoplasmic, is most likely complexed with other ATPase
      subunits in the membrane fraction. An additional three proteins predicted to be
      cytoplasmic but found in the membrane fraction, may be cytoplasmic contaminants.
      These include a chaperone homolog that may have attached to denatured membrane
      proteins during cell fractionation. Omitting these three proteins would boost the
      membrane-protein predictability of the models to near 80%. A consensus prediction
      using all six programs for all 2242 ORFs in the P. furiosus genome estimates that
      24% of the ORF products are found in the membrane. However, this is likely to be
      a minimum value due to the programs' inability to recognize certain membrane
      related proteins, such as subunits associated with membrane complexes and porin
      type proteins.

PMID- 18629241
TI  - ESF Workshop 'Proteomics: Focus on Protein Interactions'.

PMID- 18629242
TI  - Sphingoid base metabolism in yeast: mapping gene expression patterns into
      qualitative metabolite time course predictions.
AB  - Can qualitative metabolite time course predictions be inferred from measured mRNA
      expression patterns? Speaking against this possibility is the large number of
      'decoupling' control points that lie between these variables, i.e. translation,
      protein degradation, enzyme inhibition and enzyme activation. Speaking for it is
      the notion that these control points might be coordinately regulated such that
      action exerted on the mRNA level is informative of action exerted on the protein
      and metabolite levels. A simple kinetic model of sphingoid base metabolism in
      yeast is postulated. When the enzyme activities in this model are modulated
      proportional to mRNA expression levels measured in heat shocked yeast, the model
      yields a transient rise and fall in sphingoid bases followed by a permanent rise
      in ceramide. This finding is in qualitative agreement with experiments and is
      thus consistent with the aforementioned coordinated control system hypothesis.

PMID- 18629243
TI  - Meeting review: the Bioinformatics Open Source Conference 2001 (BOSC 2001).

PMID- 18629244
TI  - Website review: protein-protein interactions on the web.
AB  - We present a brief guide to resources on the Internet relating to Protein-Protein
      Interactions. These include databases containing experimentally verified and
      computationally inferred physical and functional interactions. There are also
      tools for predicting interactions and for extracting information on interactions
      from the literature, and organism specific databases.

PMID- 18629245
TI  - The ESF programme on integrated approaches for Functional Genomics Workshop on
      'Proteomics: Focus on Protein Interactions'.

PMID- 18629246
TI  - Protein arrays: issues to be addressed.
AB  - Protein arrays are fast becoming established as a means to monitor protein
      expression levels and investigate protein interactions and function. They present
      particular technical demands that will need to be solved in order to achieve the
      maximum capability of efficient and sensitive protein analysis in the high
      throughput setting of functional genomics. The following resume of some major
      issues around this new technology was made as the chairperson's introduction to
      the workshop session on peptide and protein chips.

PMID- 18629247
TI  - Mapping protein-protein interactions with combinatorial peptides.

PMID- 18629248
TI  - iSPOT: a web tool for the analysis and recognition of protein domain specificity.
AB  - Methods that aim at predicting interaction partners are very likely to play an
      important role in the interpretation of genomic information. iSPOT (iSpecificity
      Prediction Of Target) is a web tool (accessible at
      http://cbm.bio.uniroma2.it/iSPOT) developed for the prediction of protein-protein
      interaction mediated by families of peptide recognition modules. iSPOT accesses a
      database of position specific residue-residue interaction frequencies for members
      of the SH3 and PDZ protein domain families. The software utilises this database
      to provide a score for any potential domain peptide interaction.ISPOT: 1.
      evaluates the likelihood of the interaction between any of the peptides contained
      in an input protein and a list of domains of the two different families; 2.
      searches in the SWISS-PROT database for potential partners of a query domain; and
      3. has access to a repository of all the domain/target peptide interaction data.

PMID- 18629249
TI  - Synthetic peptide and protein domain arrays prepared by the SPOT technology.
AB  - The SPOT(trade mark) technology for highly parallel synthesis of peptides on flat
      surfaces in array type format has evolved into a versatile toolbox for a variety
      of applications in proteomics such as mapping protein-protein interactions and
      profiling the substrate specificity of enzymes such as kinases and proteases.
      Originally developed for the synthesis of short overlapping peptide sequences for
      mapping antibody epitopes this technology has recently been extended to the
      synthesis of functional protein domains. This opens up a variety of future
      applications such as target identification and protein expression profiling.

PMID- 18629250
TI  - Proteome analysis of the plasma membrane of Mycobacterium tuberculosis.
AB  - The plasma membrane of Mycobacterium tuberculosis is likely to contain proteins
      that could serve as novel drug targets, diagnostic probes or even components of a
      vaccine against tuberculosis. With this in mind, we have undertaken proteome
      analysis of the membrane of M. tuberculosis H37Rv. Isolated membrane vesicles
      were extracted with either a detergent (Triton X114) or an alkaline buffer
      (carbonate) following two of the protocols recommended for membrane protein
      enrichment. Proteins were resolved by 2D-GE using immobilized pH gradient (IPG)
      strips, and identified by peptide mass mapping utilizing the M. tuberculosis
      genome database. The two extraction procedures yielded patterns with minimal
      overlap. Only two proteins, both HSPs, showed a common presence. MALDI-MS
      analysis of 61 spots led to the identification of 32 proteins, 17 of which were
      new to the M. tuberculosis proteome database. We classified 19 of the identified
      proteins as 'membrane-associated'; 14 of these were further classified as
      'membrane-bound', three of which were lipoproteins. The remaining proteins
      included four heat-shock proteins and several enzymes involved in energy or lipid
      metabolism. Extraction with Triton X114 was found to be more effective than
      carbonate for detecting 'putative' M. tuberculosis membrane proteins. The
      protocol was also found to be suitable for comparing BCG and M. tuberculosis
      membranes, identifying ESAT-6 as being expressed selectively in M. tuberculosis.
      While this study demonstrates for the first time some of the membrane proteins of
      M. tuberculosis, it also underscores the problems associated with proteomic
      analysis of a complex membrane such as that of a mycobacterium.

PMID- 18629251
TI  - Flowering buds of globular proteins: transpiring simplicity of protein
      organization.
AB  - Structural and functional complexity of proteins is dramatically reduced to a
      simple linear picture when the laws of polymer physics are considered. A basic
      unit of the protein structure is a nearly standard closed loop of 25-35 amino
      acid residues, and every globular protein is built of consecutively connected
      closed loops. The physical necessity of the closed loops had been apparently
      imposed on the early stages of protein evolution. Indeed, the most frequent
      prototype sequence motifs in prokaryotic proteins have the same sequence size,
      and their high match representatives are found as closed loops in crystallized
      proteins. Thus, the linear organization of the closed loop elements is a
      quintessence of protein evolution, structure and folding.

PMID- 18629252
TI  - The annotation of RNA motifs.
AB  - The recent deluge of new RNA structures, including complete atomic-resolution
      views of both subunits of the ribosome, has on the one hand literally overwhelmed
      our individual abilities to comprehend the diversity of RNA structure, and on the
      other hand presented us with new opportunities for comprehensive use of RNA
      sequences for comparative genetic, evolutionary and phylogenetic studies. Two
      concepts are key to understanding RNA structure: hierarchical organization of
      global structure and isostericity of local interactions. Global structure changes
      extremely slowly, as it relies on conserved long-range tertiary interactions.
      Tertiary RNA-RNA and quaternary RNA-protein interactions are mediated by RNA
      motifs, defined as recurrent and ordered arrays of non-Watson-Crick base-pairs. A
      single RNA motif comprises a family of sequences, all of which can fold into the
      same three-dimensional structure and can mediate the same interaction(s). The
      chemistry and geometry of base pairing constrain the evolution of motifs in such
      a way that random mutations that occur within motifs are accepted or rejected
      insofar as they can mediate a similar ordered array of interactions. The steps
      involved in the analysis and annotation of RNA motifs in 3D structures are: (a)
      decomposition of each motif into non-Watson-Crick base-pairs; (b) geometric
      classification of each basepair; (c) identification of isosteric substitutions
      for each basepair by comparison to isostericity matrices; (d) alignment of
      homologous sequences using the isostericity matrices to identify corresponding
      positions in the crystal structure; (e) acceptance or rejection of the null
      hypothesis that the motif is conserved.

PMID- 18629253
TI  - International Summer School, ' From Genome to Life'.
AB  - This report from the International Summer School 'From Genome to Life', held at
      the Institute d'Etudes Scientifiques de Cargese in Corsica in July 2002, covers
      the talks of the invited speakers. The topics of the talks can be broadly grouped
      into the areas of genome annotation, comparative and evolutionary genomics,
      functional genomics, proteomics, structural genomics, pharmacogenomics, and
      organelle genomes, epigenetics and RNA.

PMID- 18629254
TI  - Correct assignment of homology is crucial when genomics meets molecular
      evolution.
AB  - Pertinent evolutionary studies are based on a correct use of homology terms such
      as paralogues, metalogues and orthologues. Such crucial concepts have been
      applied to intragenomic and intergenomic analyses. A further requisite is a
      proper definition of what is a structural segment of homology. Such segments are
      called modules to reflect that they play a role in the mechanism of combinational
      construction of a gene from ready-made basic components. Since identifying a
      module is operationally equivalent to determining the ancestor to this gene
      segment, it becomes possible to track back protein history and genome evolution.
      Such studies underline the importance of two fundamental processes, gene
      duplication and gene fusion. Moreover, grouping the closest orthologues in
      families is a pertinent way to reconstruct a genomic tree for all available
      prokaryotes.

PMID- 18629255
TI  - Learning about gene regulatory networks from gene deletion experiments.
AB  - Gene regulatory networks are a major focus of interest in molecular biology. A
      crucial question is how complex regulatory systems are encoded and controlled by
      the genome. Three recent publications have raised the question of what can be
      learned about gene regulatory networks from microarray experiments on gene
      deletion mutants. Using this indirect approach, topological features such as
      connectivity and modularity have been studied.

PMID- 18629257
TI  - The evolution of light stress proteins in photosynthetic organisms.
AB  - The Elip (early light-inducible protein) family in pro- and eukaryotic
      photosynthetic organisms consists of more than 100 different stress proteins.
      These proteins accumulate in photosynthetic membranes in response to light stress
      and have photoprotective functions. At the amino acid level, members of the Elip
      family are closely related to light-harvesting chlorophyll a/b-binding (Cab)
      antenna proteins of photosystem I and II, present in higher plants and some
      algae. Based on their predicted secondary structure, members of the Elip family
      are divided into three groups: (a) one-helix Hlips (high light-induced proteins),
      also called Scps (small Cab-like proteins) or Ohps (one-helix proteins); (b) two
      helix Seps (stress-enhanced proteins); and (c) three-helix Elips and related
      proteins. Despite having different physiological functions it is believed that
      eukaryotic three-helix Cab proteins evolved from the prokaryotic Hlips through a
      series of duplications and fusions. In this review we analyse the occurrence of
      Elip family members in various photosynthetic prokaryotic and eukaryotic
      organisms and discuss their evolutionary relationship with Cab proteins.

PMID- 18629258
TI  - Intelligent Systems for Molecular Biology 2002 (ISMB02).
AB  - This report profiles the keynote talks given at ISMB02 in Edmonton, Canada, by
      Michael Ashburner, Barry Honig, Isidore Rigoutsos, Ford Doolittle, Stephen
      Altschul, Terry Gaasterland, John Reinitz, and the Overton Prize winner, David
      Baker.

PMID- 18629259
TI  - Heterologous expression and purification systems for structural proteomics of
      mammalian membrane proteins.
AB  - Membrane proteins (MPs) are responsible for the interface between the exterior
      and the interior of the cell. These proteins are implicated in numerous diseases,
      such as cancer, cystic fibrosis, epilepsy, hyperinsulinism, heart failure,
      hypertension and Alzheimer's disease. However, studies on these disorders are
      hampered by a lack of structural information about the proteins involved.
      Structural analysis requires large quantities of pure and active proteins. The
      majority of medically and pharmaceutically relevant MPs are present in tissues at
      very low concentration, which makes heterologous expression in large-scale
      production-adapted cells a prerequisite for structural studies. Obtaining
      mammalian MP structural data depends on the development of methods that allow the
      production of large quantities of MPs. This review focuses on the different
      heterologous expression systems, and the purification strategies, used to produce
      large amounts of pure mammalian MPs for structural proteomics.

PMID- 18629260
TI  - Endogenous retroviruses and human evolution.
AB  - Humans share about 99% of their genomic DNA with chimpanzees and bonobos; thus,
      the differences between these species are unlikely to be in gene content but
      could be caused by inherited changes in regulatory systems. Endogenous
      retroviruses (ERVs) comprise approximately 5% of the human genome. The LTRs of
      ERVs contain many regulatory sequences, such as promoters, enhancers,
      polyadenylation signals and factor-binding sites. Thus, they can influence the
      expression of nearby human genes. All known human-specific LTRs belong to the
      HERV-K (human ERV) family, the most active family in the human genome. It is
      likely that some of these ERVs could have integrated into regulatory regions of
      the human genome, and therefore could have had an impact on the expression of
      adjacent genes, which have consequently contributed to human evolution. This
      review discusses possible functional consequences of ERV integration in active
      coding regions.

PMID- 18629261
TI  - Harvesting the mouse genome.
AB  - The sequencing of the black 6 mouse (strain C57Bl/6) has reached an important
      juncture. The BAC fingerprint map is almost complete, the BACs have been
      endsequenced and a seven-fold coverage whole-genome shotgun has been assembled.
      Now the BAC-by-BAC sequencing phase is under way and in-depth comparative
      analysis can be carried out on regions that have been the subject of targeted
      sequencing. This paper reviews the progress so far and looks forward to the
      promises of finished sequence.

PMID- 18629262
TI  - Microarray analysis of campylobacter jejuni: to the guts of the problem!

PMID- 18629263
TI  - Microarray-based comparative genomics: genome plasticity in Mycobacterium bovis.

PMID- 18629264
TI  - Heterologous array analysis in Pinaceae: hybridization of Pinus taeda cDNA arrays
      with cDNA from needles and embryogenic cultures of P. Taeda, P. Sylvestris or
      Picea abies.
AB  - Hybridization of labelled cDNA from various cell types with high-density arrays
      of expressed sequence tags is a powerful technique for investigating gene
      expression. Few conifer cDNA libraries have been sequenced. Because of the high
      level of sequence conservation between Pinus and Picea we have investigated the
      use of arrays from one genus for studies of gene expression in the other. The
      partial cDNAs from 384 identifiable genes expressed in differentiating xylem of
      Pinus taeda were printed on nylon membranes in randomized replicates. These were
      hybridized with labelled cDNA from needles or embryogenic cultures of Pinus
      taeda, P. sylvestris and Picea abies, and with labelled cDNA from leaves of
      Nicotiana tabacum. The Spearman correlation of gene expression for pairs of
      conifer species was high for needles (r(2) = 0.78 - 0.86), and somewhat lower for
      embryogenic cultures (r(2) = 0.68 - 0.83). The correlation of gene expression for
      tobacco leaves and needles of each of the three conifer species was lower but
      sufficiently high (r(2) = 0.52 - 0.63) to suggest that many partial gene
      sequences are conserved in angiosperms and gymnosperms. Heterologous probing was
      further used to identify tissue-specific gene expression over species boundaries.
      To evaluate the significance of differences in gene expression, conventional
      parametric tests were compared with permutation tests after four methods of
      normalization. Permutation tests after Z-normalization provide the highest degree
      of discrimination but may enhance the probability of type I errors. It is
      concluded that arrays of cDNA from loblolly pine are useful for studies of gene
      expression in other pines or spruces.

PMID- 18629265
TI  - Microarrays for bacterial pathogens - hope or hype?

PMID- 18629266
TI  - Haemophilus influenzae microarrays: virulence and vaccines.
AB  - In 1995 the genome sequence of the Haemophilus influenzae KW20 (Rd) strain was
      published, the first available for a free-living organism. The genome has been
      invaluable in global strategies to identify certain virulence-related genes, e.g.
      those involved in LPS synthesis, and also essential genes, but there is a paucity
      of wholegenome transcriptome studies. We have now constructed a whole-genome
      array consisting of genes from Rd, additional genes identified in other strains
      of H. influenzae and controls (from eukaryotic sources and other bacteria). We
      intend to use this array in studies aimed at understanding the bacterium's basic
      metabolism and its response to changing environments; deciphering global
      regulatory networks (by comparison of wild-type and mutant strains); and
      identifying genes expressed in vivo. The use of H. influenzae DNA arrays combined
      with proteomic approaches will enhance our understanding of the metabolism and
      virulence of the organism. Additionally, the genome sequence of a non-typable H.
      influenzae strain is in progress. The sequence from this isolate will be
      invaluable not only in identifying potential novel antibiotic targets and
      putative vaccine candidates but also in the design of a microarray for genome
      typing purposes.

PMID- 18629267
TI  - In vitro gene expression dissected: chemostat surgery for mycobacterium
      tuberculosis.
AB  - A unique approach, combining defined and reproducible in vitro models with DNA
      microarrays, has been developed to study environmental modulation of
      mycobacterial gene expression. The gene expression profiles of samples of
      Mycobacterium tuberculosis, from independent chemostat cultures grown under
      defined and reproducible conditions, were found to be highly correlated. This
      approach is now being used to study the effect of relevant stimuli, such as
      limited oxygen availability, on mycobacterial gene expression. A modification of
      the chemostat culture system, enabling large-volume controlled batch culture, has
      been developed to study starvation survival. Cultures of M. tuberculosis have
      been maintained under nutrient-starved conditions for extended periods, with
      10(6) - 10(7) bacilli surviving in a culturable state after 100 days. The design
      of the culture system has made it possible to control the environment and collect
      multiple time-course samples to study patterns of gene expression. These studies
      demonstrate that it is possible to perform long-term studies and obtain
      reproducible expression data using controlled and defined in vitro models.

PMID- 18629269
TI  - Microarrays for public health: genomic epidemiology of tuberculosis.
AB  - In response to a large local school-based outbreak of tuberculosis, we have been
      evaluating the utility of microarray bacterial genomic analysis in outbreak
      management. After initial comparison of the isolate from the index case with
      Mycobacterium tuberculosis H37Rv, it was possible to design robust PCRs directed
      towards strain-specific deletions. Rapid PCR analysis of isolates proved valuable
      in determining whether or not other isolates were compatible with the outbreak
      strain and further microarray studies revealed genetic markers that could be used
      to discriminate between locally circulating strains.We suggest that this approach
      forms the basis for developing rapid local genotyping schemes applicable to M.
      tuberculosis and that application to other pathogens warrants consideration.

PMID- 18629271
TI  - The curse of normalization.
AB  - Despite its enormous promise to further our understanding of cellular processes
      involved in the regulation of gene expression, microarray technology generates
      data for which statistical pre-processing has become a necessity before any
      interpretation of data can begin. The process by which we distinguish (and
      remove) non-biological variation from biological variation is called
      normalization. With a multitude of experimental designs, techniques and
      technologies influencing the acquisition of data, numerous approaches to
      normalization have been proposed in the literature. The purpose of this short
      review is not to add to the many suggestions that have been made, but to discuss
      some of the difficulties we encounter when analysing microarray data.

PMID- 18629272
TI  - Microarray analysis of bacterial gene expression: towards the regulome.
AB  - Microarray technology allows co-regulated genes to be identified. In order to
      identify genes that are controlled by specific regulators, gene expression can be
      compared in mutant and wild-type bacteria. However, there are a number of
      pitfalls with this approach; in particular, the regulator may not be active under
      the conditions in which the wild-type strain is cultured. Once co-regulated genes
      have been identified, proteinbinding motifs can be identified. By combining these
      data with a map of promoters, or operons (the operome), the regulatory networks
      in the cell (the regulome) can start to be built up.

PMID- 18629273
TI  - The heat shock response of Mycobacterium tuberculosis: linking gene expression,
      immunology and pathogenesis.
AB  - The regulation of heat shock protein (HSP) expression is critically important to
      pathogens such as Mycobacterium tuberculosis and dysregulation of the heat shock
      response results in increased immune recognition of the bacterium and reduced
      survival during chronic infection. In this study we use a whole genome spotted
      microarray to characterize the heat shock response of M. tuberculosis. We also
      begin a dissection of this important stress response by generating deletion
      mutants that lack specific transcriptional regulators and examining their
      transcriptional profiles under different stresses. Understanding the stimuli and
      mechanisms that govern heat shock in mycobacteria will allow us to relate
      observed in vivo expression patterns of HSPs to particular stresses and
      physiological conditions. The mechanisms controlling HSP expression also make
      attractive drug targets as part of a strategy designed to enhance immune
      recognition of the bacterium.

PMID- 18629274
TI  - Separated at birth? Microarray analysis of two strikingly similar yersinia
      species.

PMID- 18629276
TI  - The use of microarray technology for the analysis of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is an important human pathogen associated with
      pneumonia, septicaemia, meningitis and otitis media. It is estimated to result in
      over 3 million child deaths worldwide every year and an even greater number of
      deaths among the elderly. Prior to the complete sequencing of the genomes of S.
      pneumoniae TIGR4 (serotype 4) and S. pneumoniae R6 (serotype 2), we designed a
      custom miniarray consisting of 497 pneumococcal genes. The overall objectives of
      our microarray investigations were, first, to assess the genetic diversity
      between different S. pneumoniae serotypes, clinical isolates and also different
      Streptococcus species; second, we aimed to use microarray technology to examine
      the mechanisms by which environmental factors influence pneumococcal gene
      expression, and ultimately to further the understanding of how these changes in
      gene expression are achieved and how they may alter the virulence of the
      organism.

PMID- 18629277
TI  - Meeting review: Bioinformatics of biochips: accelerating discovery in functional
      genomics.

PMID- 18629278
TI  - Can replication save noisy microarray data?
AB  - Microarray experiments are multi-step processes. At each step-the growth of
      cultures, extraction of mRNA, reverse transcription, labelling, hybridization,
      scanning, and image analysis-variation and error cannot be completely avoided.
      Estimating the amount of such noise and variation is essential, not only to test
      for differential expression but also to suggest at which level replication is
      most effective.Replication and averaging are the key to the estimation as well as
      the reduction of variability. Here I discuss the use of ANOVA mixed models and of
      analysis of variance components as a rigorous way to calculate the number of
      replicates necessary to detect a given target fold-change in expression levels.
      Procedures are available in the package YASMA
      (http://www.cryst.bbk.ac.uk/wernisch/yasma.html) for the statistical data
      analysis system R (http://www.R-project.org).

PMID- 18629279
TI  - The 1st Symposium of the Wellcome Trust-Funded Multi-Collaborative Microbial
      Pathogen Microarray Facility-BmuG@S 2002: 'Bacterial Pathogens, Microarrays and
      Functional Genomics'.

PMID- 18629280
TI  - BmuG@Sbase--a microarray database and analysis tool.
AB  - The manufacture and use of a whole-genome microarray is a complex process and it
      is essential that all data surrounding the process is stored, is accessible and
      can be easily associated with the data generated following hybridization and
      scanning. As part of a program funded by the Wellcome Trust, the Bacterial
      Microarray Group at St. George's Hospital Medical School (BmuG@S) will generate
      whole-genome microarrays for 12 bacterial pathogens for use in collaboration with
      specialist research groups. BmuG@S will collaborate with these groups at all
      levels, including the experimental design, methodology and analysis. In addition,
      we will provide informatic support in the form of a database system (BmuG@Sbase).
      BmuG@Sbase will provide access through a web interface to the microarray design
      data and will allow individual users to store their data in a searchable, secure
      manner. Tools developed by BmuG@S in collaboration with specific research groups
      investigating analysis methodology will also be made available to those groups
      using the arrays and submitting data to BmuG@Sbase.

PMID- 18629281
TI  - Microarrays for Microbes: the BmuG@S Approach.

PMID- 18629282
TI  - ORF organization and gene recognition in the yeast genome.
AB  - Some rules on gene recognition and ORF organization in the Saccharomyces
      cerevisiae genome are demonstrated by statistical analyses of sequence data. This
      study includes: (a) The random frame rule-that the six reading frames W1, W2, W3,
      C1, C2 and C3 in the double-stranded genome are randomly occupied by ORFs
      (related phenomena on ORF overlapping are also discussed). (b) The inhomogeneity
      rule-coding and non-coding ORFs differ in inhomogeneity of base composition in
      the three codon positions. By use of the inhomogeneity index (IHI), one can make
      a distinction between coding (IHI > 14) and non-coding (IHI < or = 14) ORFs at
      95% accuracy. We find that 'spurious' ORFs (with IHI < or = 14) are distributed
      mainly in three classes of ORFs, namely, those with 'similarity to unknown
      proteins', those with 'no similarity', or 'questionable ORFs'. The total number
      of spurious ORFs (which are unlikely to be regarded as coding ORFs) is estimated
      to be 470. (c) The evaluation of ORF length distribution shows that below 200
      amino acids the occurrence of ATG initiator ORFs is close to random.

PMID- 18629283
TI  - Reproducibility assessment of independent component analysis of expression ratios
      from DNA microarrays.
AB  - DNA microarrays allow the measurement of transcript abundances for thousands of
      genes in parallel. Most commonly, a particular sample of interest is studied next
      to a neutral control, examining relative changes (ratios). Independent component
      analysis (ICA) is a promising modern method for the analysis of such experiments.
      The condition of ICA algorithms can, however, depend on the characteristics of
      the data examined, making algorithm properties such as robustness specific to the
      given application domain. To address the lack of studies examining the robustness
      of ICA applied to microarray measurements, we report on the stability of
      variational Bayesian ICA in this domain. Microarray data are usually preprocessed
      and transformed. Hence we first examined alternative transforms and data
      selections for the smallest modelling reconstruction errors. Log-ratio data are
      reconstructed better than non-transformed ratio data by our linear model with a
      Gaussian error term. To compare ICA results we must allow for ICA invariance
      under rescaling and permutation of the extracted signatures, which hold the
      loadings of the original variables (gene transcript ratios) on particular latent
      variables. We introduced a method to optimally match corresponding signatures
      between sets of results. The stability of signatures was then examined after (1)
      repetition of the same analysis run with different random number generator seeds,
      and (2) repetition of the analysis with partial data sets. The effects of both
      dropping a proportion of the gene transcript ratios and dropping measurements for
      several samples have been studied. In summary, signatures with a high relative
      data power were very likely to be retained, resulting in an overall stability of
      the analyses. Our analysis of 63 yeast wildtype vs. wild-type experiments,
      moreover, yielded 10 reliably identified signatures, demonstrating that the
      variance observed is not just noise.

PMID- 18629284
TI  - Methylation analysis of several tumour suppressor genes shows a low frequency of
      methylation of CDKN2A and RARB in uveal melanomas.
AB  - We have investigated the frequency of methylation of several tumour suppressor
      genes in uveal melanoma. As the loss of one copy of chromosome 3 (monosomy 3),
      which is found in about half of these tumours, is tightly associated with
      metastatic disease, a special emphasis was laid on genes located on this
      chromosome, including the fragile histidine triad (FHIT), von Hippel-Lindau
      (VHL), beta-catenin (CTNNB1), activated leukocyte cell adhesion molecule (ALCAM)
      and retinoic acid receptor-beta2 (RARB) genes. In addition, the methylation
      patterns of the CpG-rich regions 5' of the E-cadherin (CDH1), p16/cyclin
      dependent kinase inhibitor 2 A (CDKN2A) and retinoblastoma (RB1) genes were
      analysed by bisulphite genomic sequencing or methylation-specific PCR (MSP).
      Furthermore, the SNRPN and D15S63 loci, which are located in the imprinted region
      of chromosome 15, were included in the study. Aberrant methylation was detected
      in nine of 40 tumours analysed: The imprinted SNRPN and D15S63 loci were
      hypermethylated in three tumours, all of which retained both copies of chromosome
      3. Methylated RARB alleles were detected in three tumours, whereas in three other
      tumours CDKN2A was found to be methylated. As we did not find RARB and CDKN2A
      preferentially methylated in tumours with monosomy 3, which is a significant
      predictor of metastatic disease, we suggest that these genes may play a causative
      role in the formation of uveal melanoma but not in the development of metastases.

PMID- 18629286
TI  - SSRD: simple sequence repeats database of the human genome.
AB  - Simple sequence repeats are predominantly found in most organisms. They play a
      major role in studies of genetic diversity, and are useful as diagnostic markers
      for many diseases. The simple sequence repeats database (SSRD) for the human
      genome was created for easy access to such repeats, for analysis, and to be used
      to understand their biological significance. The data includes the abundance and
      distribution of SSRs in the coding and non-coding regions of the genome, as well
      as their association with the UTRs of genes. The exact locations of repeats with
      respect to genomic regions (such as UTRs, exons, introns or intergenic regions)
      and their association with STS markers are also highlighted. The resource will
      facilitate repeat sequence analysis in the human genome and the understanding of
      the functional and evolutionary significance of simple sequence repeats. SSRD is
      available through two websites, http://www.ccmb.res.in/ssr and
      http://www.ingenovis.com/ssr.

PMID- 18629288
TI  - Beenome soon: honey bees as a model 'non-model' system for comparative genomics.

PMID- 18629289
TI  - Mapping functional associations in the entire genome of Drosophila melanogaster
      using fusion analysis.
AB  - We have previously shown that the detection of gene fusion events can contribute
      towards the elucidation of functional associations of proteins within entire
      genomes. Here we have analysed the entire genome of Drosophila melanogaster using
      fusion analysis and two additional constraints that improve the reliability of
      the predictions, viz. low sequence similarity and low degree of paralogy of the
      component proteins involved in a fusion event. Imposing these constraints, the
      total number of unique component pairs is reduced from 18 654 to a mere 220
      cases, which are expected to represent some of the most reliably detected
      functionally associated proteins. Using additional information from sequence
      databases, we have been able to detect pairs of functionally associated proteins
      with important functions in cellular and developmental pathways, such as
      spermatogenesis and programmed cell death.

PMID- 18629290
TI  - Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial
      asthma and severity of the disease.
AB  - Two polymorphisms in the IL4 (G/C 3'-UTR) and IL5 (C-703T) genes were studied in
      a sample of families whose probands had atopic bronchial asthma (BA) (66
      families, n = 183) and in a group of non-cognate individuals with the severe form
      of the disease (n = 34). The samples were collected from the Russian population
      in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT),
      a significant association of allele C-703 IL5 with BA was established (TDT =
      4.923, p = 0.007 +/- 0.0007). The analysis of 40 individuals with mild asthma and
      49 patients with the severe form of the disease revealed a negative association
      of genotype GG IL4 (OR = 0.39, 95% CI = 0.15-0.99, p = 0.035), and also a trend
      towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98
      6.57, p = 0.052) with mild BA. There was a concordance of the clinical
      classification of BA severity with the 'genotype' (McNemar's chi(2) test with
      continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results
      suggest that polymorphisms in the IL4 and IL5 genes contribute to the
      susceptibility to atopic BA and could determine the clinical course of the
      disease.

PMID- 18629291
TI  - Incorporation of gene function and disease into CFG.

PMID- 18629292
TI  - Performance assessment of kernel density clustering for gene expression profile
      data.
AB  - Kernel density smoothing techniques have been used in classification or
      supervised learning of gene expression profile (GEP) data, but their applications
      to clustering or unsupervised learning of those data have not been explored and
      assessed. Here we report a kernel density clustering method for analysing GEP
      data and compare its performance with the three most widely-used clustering
      methods: hierarchical clustering, K-means clustering, and multivariate mixture
      model-based clustering. Using several methods to measure agreement, between
      cluster isolation, and withincluster coherence, such as the Adjusted Rand Index,
      the Pseudo F test, the r(2) test, and the profile plot, we have assessed the
      effectiveness of kernel density clustering for recovering clusters, and its
      robustness against noise on clustering both simulated and real GEP data. Our
      results show that the kernel density clustering method has excellent performance
      in recovering clusters from simulated data and in grouping large real expression
      profile data sets into compact and well-isolated clusters, and that it is the
      most robust clustering method for analysing noisy expression profile data
      compared to the other three methods assessed.

PMID- 18629293
TI  - Genomic analyses of transport proteins in Ralstonia metallidurans.
AB  - Ralstonia (Wautersia, Cupriavidus) metallidurans (Rme) is better able to
      withstand high concentrations of heavy metals than any other well-studied
      organism. This fact renders it a potential agent of bioremediation as well as an
      ideal model organism for understanding metal resistance phenotypes. We have
      analysed the genome of Rme for genes encoding homologues of established and
      putative transport proteins; 13% of all genes in Rme encode such homologues.
      Nearly one-third of the transporters identified (32%) appear to function in
      inorganic ion transport with three-quarters of these acting on cations.
      Transporters specific for amino acids outnumber sugar transporters nearly 3 : 1,
      and this fact plus the large number of uptake systems for organic acids indicates
      the heterotrophic preferences of these bacteria. Putative drug efflux pumps
      comprise 10% of the encoded transporters, but numerous efflux pumps for heavy
      metals, metabolites and macromolecules were also identified. The results
      presented should facilitate genetic manipulation and mechanistic studies of
      transport in this remarkable bacterium.

PMID- 18629294
TI  - A web service for biomedical term look-up.
AB  - Recent years have seen a huge increase in the amount of biomedical information
      that is available in electronic format. Consequently, for biomedical researchers
      wishing to relate their experimental results to relevant data lurking somewhere
      within this expanding universe of on-line information, the ability to access and
      navigate biomedical information sources in an efficient manner has become
      increasingly important. Natural language and text processing techniques can
      facilitate this task by making the information contained in textual resources
      such as MEDLINE more readily accessible and amenable to computational processing.
      Names of biological entities such as genes and proteins provide critical links
      between different biomedical information sources and researchers' experimental
      data. Therefore, automatic identification and classification of these terms in
      text is an essential capability of any natural language processing system aimed
      at managing the wealth of biomedical information that is available
      electronically. To support term recognition in the biomedical domain, we have
      developed Termino, a large-scale terminological resource for text processing
      applications, which has two main components: first, a database into which very
      large numbers of terms can be loaded from resources such as UMLS, and stored
      together with various kinds of relevant information; second, a finite state
      recognizer, for fast and efficient identification and mark-up of terms within
      text. Since many biomedical applications require this functionality, we have made
      Termino available to the community as a web service, which allows for its
      integration into larger applications as a remotely located component, accessed
      through a standardized interface over the web.

PMID- 18629295
TI  - A system for identifying named entities in biomedical text: how results from two
      evaluations reflect on both the system and the evaluations.
AB  - We present a maximum entropy-based system for identifying named entities (NEs) in
      biomedical abstracts and present its performance in the only two biomedical named
      entity recognition (NER) comparative evaluations that have been held to date,
      namely BioCreative and Coling BioNLP. Our system obtained an exact match F-score
      of 83.2% in the BioCreative evaluation and 70.1% in the BioNLP evaluation. We
      discuss our system in detail, including its rich use of local features, attention
      to correct boundary identification, innovative use of external knowledge
      resources, including parsing and web searches, and rapid adaptation to new NE
      sets. We also discuss in depth problems with data annotation in the evaluations
      which caused the final performance to be lower than optimal.

PMID- 18629296
TI  - Construction, verification and experimental use of two epitope-tagged collections
      of budding yeast strains.
AB  - A major challenge in the post-genomic era is the development of experimental
      approaches to monitor the properties of proteins on a proteome-wide level. It
      would be particularly useful to systematically assay protein subcellular
      localization, post-translational modifications and protein-protein interactions,
      both at steady state and in response to environmental stimuli. Development of new
      reagents and methods will enhance our ability to do so efficiently and
      systematically. Here we describe the construction of two collections of budding
      yeast strains that facilitate proteome-wide measurements of protein properties.
      These collections consist of strains with an epitope tag integrated at the C
      terminus of essentially every open reading frame (ORF), one with the tandem
      affinity purification (TAP) tag, and one with the green fluorescent protein (GFP)
      tag. We show that in both of these collections we have accurately tagged a high
      proportion of all ORFs (approximately 75% of the proteome) by confirming
      expression of the fusion proteins. Furthermore, we demonstrate the use of the TAP
      collection in performing high-throughput immunoprecipitation experiments.
      Building on these collections and the methods described in this paper, we hope
      that the yeast community will expand both the quantity and type of proteome level
      data available.

PMID- 18629297
TI  - Protein name tagging guidelines: lessons learned.
AB  - Interest in information extraction from the biomedical literature is motivated by
      the need to speed up the creation of structured databases representing the latest
      scientific knowledge about specific objects, such as proteins and genes. This
      paper addresses the issue of a lack of standard definition of the problem of
      protein name tagging. We describe the lessons learned in developing a set of
      guidelines and present the first set of inter-coder results, viewed as an upper
      bound on system performance. Problems coders face include: (a) the ambiguity of
      names that can refer to either genes or proteins; (b) the difficulty of getting
      the exact extents of long protein names; and (c) the complexity of the
      guidelines. These problems have been addressed in two ways: (a) defining the
      tagging targets as protein named entities used in the literature to describe
      proteins or protein-associated or -related objects, such as domains, pathways,
      expression or genes, and (b) using two types of tags, protein tags and long-form
      tags, with the latter being used to optionally extend the boundaries of the
      protein tag when the name boundary is difficult to determine. Inter-coder
      consistency across three annotators on protein tags on 300 MEDLINE abstracts is
      0.868 F-measure. The guidelines and annotated datasets, along with automatic
      tools, are available for research use.

PMID- 18629299
TI  - Ontology-based interactive information extraction from scientific abstracts.
AB  - Over recent years, there has been a growing interest in extracting information
      automatically or semi-automatically from the scientific literature. This paper
      describes a novel ontology-based interactive information extraction (OBIIE)
      framework and a specific OBIIE system. We describe how this system enables life
      scientists to make ad hoc queries similar to using a standard search engine, but
      where the results are obtained in a database format similar to a pre-programmed
      information extraction engine. We present a case study in which the system was
      evaluated for extracting co-factors from EMBASE and MEDLINE.

PMID- 18629301
TI  - The BioLink SIG Workshop at ISMB2004.

PMID- 18629302
TI  - Towards a semantic lexicon for biological language processing.
AB  - This paper explores the use of the resources in the National Library of
      Medicine's Unified Medical Language System (UMLS) for the construction of a
      lexicon useful for processing texts in the field of molecular biology. A lexicon
      is constructed from overlapping terms in the UMLS SPECIALIST lexicon and the UMLS
      Metathesaurus to obtain both morphosyntactic and semantic information for terms,
      and the coverage of a domain corpus is assessed. Over 77% of tokens in the domain
      corpus are found in the constructed lexicon, validating the lexicon's coverage of
      the most frequent terms in the domain and indicating that the constructed lexicon
      is potentially an important resource for biological text processing.

PMID- 18629303
TI  - A special section of papers from: ISMB BioLink 2004: "Linking Literature,
      Information and Knowledge for Biology".

PMID- 18629304
TI  - The role of exposure to phthalates from polyvinyl chloride products in the
      development of asthma and allergies: a systematic review and meta-analysis.
AB  - BACKGROUND: Phthalates from polyvinyl chloride (PVC) plastics may have adverse
      effects on airways and immunologic systems, but the evidence has not been
      reviewed systematically. OBJECTIVE: We reviewed the evidence for the role of
      exposure to phthalates from PVC products in the development of asthma and
      allergies. METHODS: We conducted a Medline database search (1950 through May
      2007) for relevant studies on the respiratory and allergic effects of exposure to
      phthalates from PVC products. RESULTS: We based this review on 27 human and 14
      laboratory toxicology studies. Two mouse inhalation experiments indicated that
      mono-2-ethylhexyl phthalate (MEHP) has the ability to modulate the immune
      response to exposure to a coallergen. The data suggested a no observed effect
      level of 30 microg MEHP/m3, calculated to be below the estimated level of human
      exposure in common environments. Case reports and series (n = 9) identified and
      verified cases of asthma that were very likely caused by fumes emitted from PVC
      film. Epidemiologic studies in adults (n = 10), mostly small studies in
      occupational settings, showed associations between heated PVC fumes and asthma
      and respiratory symptoms; studies in children (n = 5) showed an association
      between PVC surface materials in the home and the risk of asthma [fixed-effects
      model: summary odds ratio (OR), 1.55; 95% confidence interval (CI), 1.18-2.05;
      four studies] and allergies (OR, 1.32; 95% CI, 1.09-1.60; three studies).
      CONCLUSIONS: High levels of phthalates from PVC products can modulate the murine
      immune response to a coallergen. Heated PVC fumes possibly contribute to
      development of asthma in adults. Epidemiologic studies in children show
      associations between indicators of phthalate exposure in the home and risk of
      asthma and allergies. The lack of objective exposure information limits the
      epidemiologic data.

PMID- 18629305
TI  - The protective mechanism of antioxidants in cadmium-induced ototoxicity in vitro
      and in vivo.
AB  - BACKGROUND: Several heavy metals have been shown to have toxic effects on the
      peripheral and central auditory system. Cadmium (Cd2+) is an environmental
      contaminant showing a variety of adverse effects. Given the current rate of
      release into the environment, the amount of Cd2+ present in the human body and
      the incidence of Cd2+-related diseases are expected to increase. OBJECTIVE: The
      overall aim of this study was to gain further insights into the mechanism of Cd2+
      induced ototoxicity. METHODS: Cell viability, reactive oxygen species (ROS),
      mitochondrial membrane potential (MMP), cytochrome c (cyt c), phosphorylated
      extracellular signal-regulated protein kinase (p-ERK), caspases, morphologic
      change, and functional changes in HEI-OC1 cells, rat cochlear explants, and mouse
      cochlea after Cd2+ exposure were measured by flow cytometry, immunohistochemical
      staining, Western blot analysis, and auditory brainstem response (ABR) recording.
      Mechanisms underlying Cd2+ototoxicity were studied using inhibitors of different
      signaling pathways, caspases, and antioxidants. RESULTS: Cd2+ exposure caused
      cell death, ROS generation, MMP loss, cyt c release, activation of caspases, ERK
      activation, apoptosis, and finally auditory threshold shift. Cd2+ toxicity
      interfered with inhibitors of cellular signaling pathways, such as ERK and c-jun
      N-terminal kinase, and with caspase inhibitors, especially inhibitors of caspase
      9 and caspase-3. The antioxidants N-acetyl-l-cysteine and ebselen showed a
      significant protective effect on the Cd2+ toxicity. CONCLUSIONS: Cd2+ is ototoxic
      with a complex underlying mechanism. However, ROS generation may be the cause of
      the toxicity, and application of antioxidants can prevent the toxic effect.

PMID- 18629306
TI  - Recirculating air filtration significantly reduces exposure to airborne
      nanoparticles.
AB  - BACKGROUND: Airborne nanoparticles from vehicle emissions have been associated
      with adverse effects in people with pulmonary and cardiovascular disease, and
      toxicologic studies have shown that nanoparticles can be more hazardous than
      their larger-scale counterparts. Recirculating air filtration in automobiles and
      houses may provide a low-cost solution to reducing exposures in many cases, thus
      reducing possible health risks. OBJECTIVES: We investigated the effectiveness of
      recirculating air filtration on reducing exposure to incidental and intentionally
      produced airborne nanoparticles under two scenarios: while driving in traffic,
      and while generating nanomaterials using gas-phase synthesis. METHODS: We tested
      the recirculating air filtration in two commercial vehicles when driving in
      traffic, as well as in a nonventilation room with a nanoparticle generator,
      simulating a nanomaterial production facility. We also measured the time-resolved
      aerosol size distribution during the in-car recirculation to investigate how
      recirculating air filtration affects particles of different sizes. We developed a
      recirculation model to describe the aerosol concentration change during
      recirculation. RESULTS: The use of inexpensive, low-efficiency filters in
      recirculation systems is shown to reduce nanoparticle concentrations to below
      levels found in a typical office within 3 min while driving through heavy
      traffic, and within 20 min in a simulated nanomaterial production facility.
      CONCLUSIONS: Development and application of this technology could lead to
      significant reductions in airborne nanoparticle exposure, reducing possible risks
      to health and providing solutions for generating nanomaterials safely.

PMID- 18629307
TI  - Region-specific growth effects in the developing rat prostate following fetal
      exposure to estrogenic ultraviolet filters.
AB  - BACKGROUND AND OBJECTIVES: Exposure to environmental endocrine disruptors is a
      potential risk factor for humans. Many of these chemicals have been shown to
      exhibit disruption of normal cellular and developmental processes in animal
      models. Ultraviolet (UV) filters used as sunscreens in cosmetics have previously
      been shown to exhibit estrogenic activity in in vitro and in vivo assays. We
      examined the effects of two UV filters, 4-methylbenzylidene camphor (4-MBC) and 3
      benzylidene camphor (3-BC), in the developing prostate of the fetal rat. METHODS:
      Pregnant Long Evans rats were fed diets containing doses of 4-MBC and 3-BC that
      resulted in average daily intakes of these chemicals corresponding to the lowest
      observed adverse effects level (LOAEL) and the no observed adverse effects level
      (NOAEL) doses in prior developmental toxicity studies. Using digital photographs
      of serial sections from postnatal day 1 animals, we identified, contoured, and
      aligned the epithelial ducts from specific regions of the developing prostate,
      plus the accessory sex glands and calculated the total volume for each region
      from three-dimensional, surface-rendered models. RESULTS: Fetal exposure to 4-MBC
      (7.0 mg/kg body weight/day) resulted in a significant increase (p < 0.05) in
      tissue volume in the prostate and accessory sex glands. Treated males exhibited a
      62% increase in the number of ducts in the caudal dorsal prostate. Increased
      distal branching morphogenesis appears to be a consequence of exposure in the
      ventral region, resulting in a 106% increase in ductal volume. CONCLUSIONS: 4-MBC
      exposure during development of the male reproductive accessory sex glands
      exhibited classical growth effects associated with estrogenic endocrine
      disruptors. The different regional responses suggest that the two developmental
      processes of ductal outgrowth and branching morphogenesis are affected
      independently by exposure to the environmental chemicals.

PMID- 18629308
TI  - A novel role of the NRF2 transcription factor in the regulation of arsenite
      mediated keratin 16 gene expression in human keratinocytes.
AB  - BACKGROUND: Inorganic sodium arsenite (iAs) is a ubiquitous environmental
      contaminant and is associated with an increased risk of skin hyperkeratosis and
      cancer. OBJECTIVES: We investigated the molecular mechanisms underlying the
      regulation of the keratin 16 (K16) gene by iAs in the human keratinocyte cell
      line HaCaT. METHODS: We performed reverse transcriptase polymerase chain
      reaction, luciferase assays, Western blots, and electrophoretic mobility shift
      assays to determine the transcriptional regulation of the K16 gene by iAs. We
      used gene overexpression approaches to elucidate the nuclear factor erythroid
      derived 2 related factor 2 (NRF2) involved in the K16 induction. RESULTS: iAs
      induced the mRNA and protein expression of K16. We also found that the expression
      of K16 was transcriptionally induced by iAs through activator protein-1-like
      sites and an antioxidant response element (ARE) in its gene promoter region.
      Treatment with iAs also enhanced the production and translocation of the NRF2
      transcription factor, an ARE-binding protein, into the nucleus without
      modification of its mRNA expression. In addition, iAs elongated the half-life of
      the NRF2 protein. When overexpressed in HaCaT cells, NRF2 was also directly
      involved in not only the up-regulation of the detoxification gene thioredoxin but
      also K16 gene expression. CONCLUSIONS: Our data clearly indicate that the K16
      gene is a novel target of NRF2. Furthermore, our findings also suggest that NRF2
      has opposing roles in the cell--in the activation of detoxification pathways and
      in promoting the development of skin disorders.

PMID- 18629309
TI  - Activation of steroid and xenobiotic receptor (SXR, NR1I2) and its orthologs in
      laboratory, toxicologic, and genome model species.
AB  - BACKGROUND: Nuclear receptor subfamily 1, group I, member 2 (NR1I2), commonly
      known as steroid and xenobiotic receptor (SXR) in humans, is a key ligand
      dependent transcription factor responsible for the regulation of xenobiotic,
      steroid, and bile acid metabolism. The ligand-binding domain is principally
      responsible for species-specific activation of NR1I2 in response to xenobiotic
      exposure. OBJECTIVES: Our objective in this study was to create a common
      framework for screening NR1I2 orthologs from a variety of model species against
      environmentally relevant xenobiotics and to evaluate the results in light of
      using these species as predictors of xenobiotic disposition and for assessment of
      environmental health risk. METHODS: Sixteen chimeric fusion plasmid vectors
      expressing the Gal4 DNA-binding domain and species-specific NR1I2 ligand-binding
      domain were screened for activation against a spectrum of 27 xenobiotic compounds
      using a standardized cotransfection receptor activation assay. RESULTS: NR1I2
      orthologs were activated by various ligands in a dose-dependent manner. Closely
      related species show broadly similar patterns of activation; however,
      considerable variation to individual compounds exists, even among species varying
      in only a few amino acid residues. CONCLUSIONS: Interspecies variation in NR1I2
      activation by various ligands can be screened through the use of in vitro NR1I2
      activation assays and should be taken into account when choosing appropriate
      animal models for assessing environmental health risk.

PMID- 18629310
TI  - Physiologically based pharmacokinetic modeling of persistent organic pollutants
      for lifetime exposure assessment: a new tool in breast cancer epidemiologic
      studies.
AB  - BACKGROUND: Despite experimental evidence, most epidemiologic studies to date
      have not supported an association between exposure to persistent organic
      pollutants (POP) and breast cancer incidence in humans. This may be attributable
      to difficulties in estimating blood/tissue POP concentration at critical time
      periods of carcinogenesis. OBJECTIVES: In this work we aimed to develop a tool to
      estimate lifetime POP blood/tissue exposure and levels during any hypothesized
      time window of susceptibility in breast cancer development. METHODS: We developed
      a physiologically based pharmacokinetic (PBPK) model that can account for any
      given physiologic lifetime history. Using data on pregnancies, height, weight,
      and age, the model estimates the values of physiologic parameters (e.g., organ
      volume, composition, and blood flow) throughout a woman's entire life. We
      assessed the lifetime toxicokinetic profile (LTP) for various exposure scenarios
      and physiologic factors (i.e., breast-feeding, growth, pregnancy, lactation, and
      weight changes). RESULTS: Simulations for three POPs [hexachlorobenzene,
      polychlorinated biphenyl (PCB)-153, PCB-180] using different lifetime physiologic
      profiles showed that the same blood concentration at 55 years of age can be
      reached despite totally different LTP. Aside from exposure levels, lactation
      periods and weight profile history were shown to be the factors that had the
      greatest impact on the LTP. CONCLUSIONS: This new lifetime PBPK model, which
      showed the limitations of using a single sample value obtained around the time of
      diagnosis for lifetime exposure assessment, will enable researchers conducting
      environmental epidemiology studies to reduce uncertainty linked to past POP
      exposure estimation and to consider exposure during time windows that are
      hypothesized to be mechanistically critical in carcinogenesis.

PMID- 18629311
TI  - Concentrations of the sunscreen agent benzophenone-3 in residents of the United
      States: National Health and Nutrition Examination Survey 2003--2004.
AB  - BACKGROUND: The capability of benzophenone-3 (BP-3) to absorb and dissipate
      ultraviolet radiation facilitates its use as a sunscreen agent. BP-3 has other
      uses in many consumer products (e.g., as fragrance and flavor enhancer,
      photoinitiator, ultraviolet curing agent, polymerization inhibitor). OBJECTIVES:
      Our goal was to assess exposure to BP-3 in a representative sample of the U.S.
      general population > or = 6 years of age. METHODS: Using automated solid-phase
      extraction coupled to high-performance liquid chromatography-tandem mass
      spectrometry, we analyzed 2,517 urine samples collected as part of the 2003--2004
      National Health and Nutrition Examination Survey. RESULTS: We detected BP-3 in
      96.8% of the samples. The geometric mean and 95th percentile concentrations were
      22.9 microg/L (22.2 microg/g creatinine) and 1,040 microg/L (1,070 microg/g
      creatinine), respectively. Least-square geometric mean (LSGM) concentrations were
      significantly higher (p < or = 0.04) for females than for males, regardless of
      age. LSGM concentrations were significantly higher for non-Hispanic whites than
      for non-Hispanic blacks (p < or = 0.01), regardless of age. Females were more
      likely than males [adjusted odds ratio (OR) = 3.5; 95% confidence interval (95%
      CI), 1.9-6.5], and non-Hispanic whites were more likely than non-Hispanic blacks
      (adjusted OR = 6.8; 95% CI, 2.9-16.2) to have concentrations above the 95th
      percentile. CONCLUSIONS: Exposure to BP-3 was prevalent in the general U.S.
      population during 2003--2004. Differences by sex and race/ethnicity probably
      reflect differences in use of personal care products containing BP-3.

PMID- 18629312
TI  - Circulating biomarkers of inflammation, antioxidant activity, and platelet
      activation are associated with primary combustion aerosols in subjects with
      coronary artery disease.
AB  - BACKGROUND: Biomarkers of systemic inflammation have been associated with risk of
      cardiovascular morbidity and mortality. OBJECTIVES: We aimed to clarify
      associations of particulate matter (PM) air pollution with systemic inflammation
      using models based on size-fractionated PM mass and markers of primary and
      secondary aerosols. METHODS: We followed a panel of 29 nonsmoking elderly
      subjects with a history of coronary artery disease (CAD) living in retirement
      communities in the Los Angeles, California, air basin. Blood plasma biomarkers
      were measured weekly over 12 weeks and included C-reactive protein (CRP),
      fibrinogen, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor-II
      (sTNF-RII), interleukin-6 (IL-6) and its soluble receptor (IL-6sR), fibrin D
      dimer, soluble platelet selectin (sP-selectin), soluble vascular cell adhesion
      molecule-1 (sVCAM-1), intracellular adhesion molecule-1 (sICAM-1), and
      myeloperoxidase (MPO). To assess changes in antioxidant capacity, we assayed
      erythrocyte lysates for glutathione peroxidase-1 (GPx-1) and copper-zinc
      superoxide dismutase (Cu,Zn-SOD) activities. We measured indoor and outdoor home
      daily size-fractionated PM mass, and hourly pollutant gases, total particle
      number (PN), fine PM elemental carbon (EC) and organic carbon (OC), estimated
      secondary organic aerosol (SOA) and primary OC (OCpri) from total OC, and black
      carbon (BC). We analyzed data with mixed models controlling for temperature and
      excluding weeks with infections. RESULTS: We found significant positive
      associations for CRP, IL-6, sTNF-RII, and sP-selectin with outdoor and/or indoor
      concentrations of quasi-ultrafine PM < or = 0.25 microm in diameter, EC, OCpri,
      BC, PN, carbon monoxide, and nitrogen dioxide from the current-day and multiday
      averages. We found consistent positive but largely nonsignificant coefficients
      for TNF-alpha, sVCAM-1, and sICAM-1, but not fibrinogen, IL-6sR, or D-dimer. We
      found inverse associations for erythrocyte Cu,Zn-SOD with these pollutants and
      other PM size fractions (0.25-2.5 and 2.5-10 microm). Inverse associations of GPx
      1 and MPO with pollutants were largely nonsignificant. Indoor associations were
      often stronger for estimated indoor EC, OCpri, and PN of outdoor origin than for
      uncharacterized indoor measurements. There was no evidence for positive
      associations with SOA. CONCLUSIONS: Results suggest that traffic emission sources
      of OCpri and quasi-ultrafine particles lead to increased systemic inflammation
      and platelet activation and decreased antioxidant enzyme activity in elderly
      people with CAD.

PMID- 18629313
TI  - A comparison of particulate matter from biomass-burning rural and non-biomass
      burning urban households in northeastern China.
AB  - BACKGROUND: Biomass fuel is the primary source of domestic fuel in much of rural
      China. Previous studies have not characterized particle exposure through time
      activity diaries or personal monitoring in mainland China. OBJECTIVES: In this
      study we characterized indoor and personal particle exposure in six households in
      northeastern China (three urban, three rural) and explored differences by
      location, cooking status, activity, and fuel type. Rural homes used biomass.
      Urban homes used a combination of electricity and natural gas. METHODS:
      Stationary monitors measured hourly indoor particulate matter (PM) with an
      aerodynamic diameter < or = 10 microm (PM10) for rural and urban kitchens, urban
      sitting rooms, and outdoors. Personal monitors for PM with an aerodynamic
      diameter < or = 2.5 microm (PM2.5) were employed for 10 participants. Time
      activity patterns in 30-min intervals were recorded by researchers for each
      participant. RESULTS: Stationary monitoring results indicate that rural kitchen
      PM10 levels are three times higher than those in urban kitchens during cooking.
      PM10 was 6.1 times higher during cooking periods than during noncooking periods
      for rural kitchens. Personal PM2.5 levels for rural cooks were 2.8-3.6 times
      higher than for all other participant categories. The highest PM2.5 exposures
      occurred during cooking periods for urban and rural cooks. However, rural cooks
      had 5.4 times higher PM2.5 levels during cooking than did urban cooks. Rural
      cooks spent 2.5 times more hours per day cooking than did their urban
      counterparts. CONCLUSIONS: These findings indicate that biomass burning for
      cooking contributes substantially to indoor particulate levels and that this
      exposure is particularly elevated for cooks. Second-by-second personal PM2.5
      exposures revealed differences in exposures by population group and strong
      temporal heterogeneity that would be obscured by aggregate metrics.

PMID- 18629314
TI  - Unmodified CdSe quantum dots induce elevation of cytoplasmic calcium levels and
      impairment of functional properties of sodium channels in rat primary cultured
      hippocampal neurons.
AB  - BACKGROUND: The growing applications of nanotechnologic products, such as quantum
      dots (QDs), increase the likelihood of exposure. Furthermore, their accumulation
      in the bioenvironment and retention in cells and tissues are arousing increasing
      worries about the potentially harmful side effects of these nanotechnologic
      products. Previous studies concerning QD cytotoxicity focused on the reactive
      oxygen species produced by QDs. Cellular calcium homeostasis dysregulation caused
      by QDs may be also responsible for QD cytotoxicity. Meanwhile the interference of
      QDs with voltage-gated sodium channel (VGSC) current (I(Na)) may lead to changes
      in electrical activity and worsen neurotoxicologic damage. OBJECTIVE: We aimed to
      investigate the potential for neurotoxicity of cadmium selenium QDs in a
      hippocampal neuronal culture model, focusing on cytoplasmic calcium levels and
      VGSCs function. METHODS: We used confocal laser scanning and standard whole-cell
      patch clamp techniques. RESULTS: We found that a) QDs induced neuron death dose
      dependently; b) cytoplasmic calcium levels were elevated for an extended period
      by QD treatment, which was due to both extracellular calcium influx and internal
      calcium release from endoplasmic reticulum; and c) QD treatment enhanced
      activation and inactivation of I(Na), prolonged the time course of activation,
      slowed I(Na) recovery, and reduced the fraction of available VGSCs. CONCLUSION:
      Results in this study provide new insights into QD toxicology and reveal
      potential risks of their future applications in biology and medicine.

PMID- 18629315
TI  - Early-onset endocrine disruptor-induced prostatitis in the rat.
AB  - BACKGROUND: Androgens are critical for specifying prostate development, with the
      fetal prostate sensitive to altered hormone levels and endocrine-disrupting
      chemicals (EDCs) that exhibit estrogenic or antiandrogenic properties. Prostatic
      inflammation (prostatitis) affects 9% of men of all ages, and > 90% of cases are
      of unknown etiology. OBJECTIVES: In this study we aimed to evaluate effects of in
      utero exposure to the antiandrogenic EDC vinclozolin, during the period of male
      reproductive tract development, on neonatal, prepubertal, and postpubertal
      prostate gland function of male offspring. METHODS: Fetal rats were exposed to
      vinclozolin (100 mg/kg body weight) or vehicle control (2.5 mL/kg body weight) in
      utero from gestational day 14 (GD14) to GD19 via oral administration to pregnant
      dams. Tissue analysis was carried out when male offspring were 0, 4, or 8 weeks
      of age. RESULTS: In utero exposure to vinclozolin was insufficient to perturb
      prostatic development and branching, although expression of androgen receptor and
      mesenchymal fibroblast growth factor-10 was down-regulated. Prostate histology
      remained normal until puberty, but 100% of animals displayed prostatitis
      postpubertally (56 days of age). Prostatic inflammation was associated with
      phosphorylation and nuclear translocation of nuclear factor-kappa B (NFkappaB)
      and postpubertal activation of proinflammatory NFkappaB-dependent genes,
      including the chemokine interleukin-8 and the cytokine transforming growth factor
      beta1. Significantly, inflammation arising from vinclozolin exposure was not
      associated with the emergence of premalignant lesions, such as prostatic intra
      epithelial neoplasia or proliferative inflammatory atrophy, and hence mimics
      nonbacterial early-onset prostatitis that commonly occurs in young men.
      CONCLUSIONS: These data are the first to unequivocally implicate EDCs as a
      causative factor and fill an important knowledge gap on the etiology of
      prostatitis.

PMID- 18629316
TI  - Brevetoxin forms covalent DNA adducts in rat lung following intratracheal
      exposure.
AB  - BACKGROUND: Human exposure to brevetoxins produced by the red tide organism,
      Karenia brevis, is an increasing public health concern. Using in vitro exposure
      of rat liver cells to brevetoxin B (PbTx-2), the primary toxin product of K.
      brevis, we previously showed that it formed C(27,28)-epoxy brevetoxin metabolites
      capable of covalently binding to nucleic acids, a common initiation step for
      carcinogenesis. OBJECTIVE: This study was undertaken to evaluate nucleic acid
      adduction in lung following in vitro and in vivo brevetoxin exposures. METHODS:
      To clarify reactions of brevetoxin epoxide with DNA, we analyzed reaction
      products of PbTx-6 (a C(27,28) epoxide metabolite of brevetoxin B) with
      nucleosides. We also analyzed adducts from nucleic acid hydrolysates of isolated
      rat lung cells treated with PbTx-2 or PbTx-6 in vitro and lung tissue from rats
      after intratracheal exposure to PbTx-2 or PbTx-6 at 45 microg toxin/kg body
      weight. RESULTS: Our results indicate that PbTx-2 forms DNA adducts with cytidine
      after treatment of isolated lung cells, and forms DNA adducts with adenosine and
      guanosine after intratracheal exposure. CONCLUSIONS: These results are consistent
      with metabolic activation of highly reactive brevetoxin intermediates that bind
      to nucleic acid. These findings provide a basis for monitoring exposure and
      assessing the hazard associated with depurination of brevetoxin-nucleotide
      adducts in lung tissue.

PMID- 18629318
TI  - Association of lead exposure with survival in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Reasons for the variability in survival among ALS cases are unknown
      but may include exposure to environmental neurotoxicants. OBJECTIVES: We aimed to
      determine whether lead exposure, assessed by measuring blood and bone lead
      levels, is associated with survival in amyotrophic lateral sclerosis (ALS).
      METHODS: We evaluated the relationship of lead exposure to ALS survival in 110
      cases from a case-control study conducted in New England in 1993-1996 that
      included measurements of blood and bone lead. We retrieved information on date
      and cause of death through 31 December 2003 from the National Death Index Plus
      and the Social Security Administration Death Index. We evaluated the relationship
      of survival to lead exposure using Cox proportional hazard analysis, with
      adjustment for age, sex, and smoking. RESULTS: We found mortality data for 100 of
      110 cases; 93 of 100 death certificates mentioned ALS. Median survival from
      diagnosis to death was 28 months. Shorter survival was associated with older age
      at diagnosis, female sex, bulbar onset, shorter interval between symptom onset
      and diagnosis, and reduced lung function. Shorter survival from diagnosis to
      death had a weak inverse association with blood lead (hazard ratio = 0.9; 95%
      confidence interval, 0.8-1.0) and a stronger inverse association with patella
      lead (0.5; 0.2-1.0) and tibia lead (0.3; 0.1-0.7); similar results were found for
      survival from symptom onset to death. CONCLUSIONS: These results suggest that
      lead exposure is associated with longer survival in ALS cases and, if confirmed,
      may shed light on mechanisms involved in disease progression.

PMID- 18629317
TI  - Diesel exhaust inhalation elicits acute vasoconstriction in vivo.
AB  - BACKGROUND: Traffic-related air pollution is consistently associated with
      cardiovascular morbidity and mortality. Recent human and animal studies suggest
      that exposure to air pollutants affects vascular function. Diesel exhaust (DE) is
      a major source of traffic-related air pollution. OBJECTIVES: Our goal was to
      study the effects of short-term exposure to DE on vascular reactivity and on
      mediators of vascular tone. METHODS: In a double-blind, crossover, controlled
      exposure study, 27 adult volunteers (10 healthy and 17 with metabolic syndrome)
      were exposed in randomized order to filtered air (FA) and each of two levels of
      diluted DE (100 or 200 microg/m(3) of fine particulate matter) in 2-hr sessions.
      Before and after each exposure, we assessed the brachial artery diameter (BAd) by
      B-mode ultrasound and collected blood samples for endothelin-1 (ET-1) and
      catecholamines. Postexposure we also assessed endothelium-dependent flow-mediated
      dilation (FMD). RESULTS: Compared with FA, DE at 200 microg/m(3) elicited a
      decrease in BAd (0.11 mm; 95% confidence interval, 0.02-0.18), and the effect
      appeared linearly dose related with a smaller effect at 100 microg/m(3). Plasma
      levels of ET-1 increased after 200 microg/m(3) DE but not after FA (p = 0.01).
      There was no consistent impact of DE on plasma catecholamines or FMD.
      CONCLUSIONS: These results demonstrate that short-term exposure to DE is
      associated with acute endothelial response and vasoconstriction of a conductance
      artery. Elucidation of the signaling pathways controlling vascular tone that
      underlie this observation requires further study.

PMID- 18629319
TI  - Meeting report: measuring endocrine-sensitive endpoints within the first years of
      life.
AB  - An international workshop titled "Assessing Endocrine-Related Endpoints within
      the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario,
      Canada. Representatives from a number of pregnancy cohort studies in North
      America and Europe presented options for measuring various endocrine-sensitive
      endpoints in early life and discussed issues related to performing and using
      those measures. The workshop focused on measuring reproductive tract
      developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and
      infant anthropometry. To the extent possible, workshop participants strove to
      develop or recommend standardized measurements that would allow comparisons and
      pooling of data across studies. The recommended outcomes include thigh fat fold,
      breast size, vaginal cytology, AGD, location of the testis, testicular size, and
      growth of the penis, with most of the discussion focusing on the genital exam.
      Although a number of outcome measures recommended during the genital exam have
      been associated with exposure to endocrine-disrupting chemicals, little is known
      about how predictive these effects are of later reproductive health or other
      chronic health conditions.

PMID- 18629320
TI  - Associations between arsenic in drinking water and pterygium in southwestern
      Taiwan.
AB  - BACKGROUND: Pterygium is a fibrovascular growth of the bulbar conjunctiva and
      underlying subconjunctival tissue that may cause blindness. The mechanism of
      pterygium formation is not yet fully understood, but pterygium has some tumorlike
      features. OBJECTIVES: The objective of this study was to evaluate the association
      between arsenic exposure through drinking water and the occurrence of pterygium
      in southwestern Taiwan. METHODS: We recruited participants > 40 years of age from
      three villages in the arseniasis-endemic area in southwestern Taiwan (exposure
      villages) and four neighboring nonendemic villages (comparison villages). Each
      participant received an eye examination and a questionnaire interview.
      Photographs taken of both eyes were later graded by an ophthalmologist to
      determine pterygium status. RESULTS: We included 223 participants from the
      exposure villages and 160 from the comparison villages. The prevalence of
      pterygium was higher in the exposure villages across all age groups in both sexes
      and increased with cumulative arsenic exposure. We found a significant
      association between cumulative arsenic exposure and the prevalence of pterygium.
      After adjusting for age, sex, working under sunlight, and working in sandy
      environments, we found that cumulative arsenic exposure of 0.1-15.0 mg/L-year and
      > or = 15.1 mg/L-year were associated with increased risks of developing
      pterygium. The adjusted odds ratios were 2.04 [95% confidence interval (CI), 1.04
      3.99] and 2.88 (95% CI, 1.42-5.83), respectively. CONCLUSIONS: Chronic exposure
      to arsenic in drinking water was related to the occurrence of pterygium, and the
      association was still observed after adjusting for exposures to sunlight and
      sandy environments.

PMID- 18629321
TI  - Association of environmental toxicants and conduct disorder in U.S. children:
      NHANES 2001-2004.
AB  - OBJECTIVE: The purpose of this study was to examine the association of tobacco
      smoke and environmental lead exposure with conduct disorder (CD). METHODS: The
      National Health and Nutrition Examination Survey (NHANES) 2001-2004 is a
      nationally representative cross-sectional sample of the noninstitutionalized U.S.
      population. We examined the association of prenatal tobacco, postnatal tobacco,
      and environmental lead exposure with CD in children 8-15 years of age (n =
      3,081). We measured prenatal tobacco exposure by parent report of cigarette use
      during pregnancy, and postnatal tobacco using serum cotinine levels. We assessed
      lead exposure using current blood lead concentration. Parents completed the
      Diagnostic Interview Schedule for Children to determine whether their children
      met criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition (DSM-IV ) for CD. RESULTS: Overall, 2.06% of children met DSM-IV criteria
      for CD in the past year, equivalent to 560,000 U.S. children 8-15 years of age.
      After adjustment, prenatal tobacco exposure was associated with increased odds
      for CD [odds ratio (OR) = 3.00; 95% confidence interval (CI), 1.36-6.63].
      Increased blood lead levels (fourth vs. first quartile) and serum cotinine levels
      (fifth vs. first quintile) were associated with an 8.64-fold (95% CI, 1.87-40.04)
      and 9.15-fold (95% CI, 1.47-6.90) increased odds of meeting DSM-IV CD criteria.
      Increasing serum cotinine levels and blood lead levels were also associated with
      increased prevalence of CD symptoms (symptom count ratio, lead: 1.73; 95% CI,
      1.23-2.43; symptom count ratio, cotinine: 1.97; 95% CI, 1.15-3.40). CONCLUSIONS:
      These results suggest that prenatal tobacco exposure and environmental lead
      exposure contribute substantially to CD in U.S. children.

PMID- 18629323
TI  - Chronic traffic-related air pollution and stress interact to predict biologic and
      clinical outcomes in asthma.
AB  - BACKGROUND: Previous research has documented effects of both physical and social
      environmental exposures on childhood asthma. However, few studies have considered
      how these two environments might interact to affect asthma. OBJECTIVE: This study
      aimed to test interactions between chronic exposure to traffic-related air
      pollution and chronic family stress in predicting biologic and clinical outcomes
      in children with asthma. METHOD: Children with asthma (n = 73, 9-18 years of age)
      were interviewed about life stress, and asthma-relevant inflammatory markers
      [cytokine production, immunoglobulin E (IgE), eosinophil counts] were measured.
      Parents reported on children's symptoms. Children completed daily diaries of
      symptoms and peak expiratory flow rate (PEFR) measures at baseline and 6 months
      later. Exposure to traffic-related air pollution was assessed using a land use
      regression model for nitrogen dioxide concentrations. RESULTS: NO(2) by stress
      interactions were found for interleukin-5 (beta for interaction term = -0.31, p =
      0.02), IgE (interaction beta = -0.29, p = 0.02), and eosinophil counts
      (interaction beta = -0.24, p = 0.04). These interactions showed that higher
      chronic stress was associated with heightened inflammatory profiles as pollution
      levels decreased. Longitudinally, NO(2) by stress interactions emerged for daily
      diary symptoms (interaction beta = -0.28, p = 0.02), parent-reported symptoms
      (interaction beta = -0.25, p = 0.07), and PEFR (interaction beta = 0.30, p =
      0.03). These interactions indicated that higher chronic stress was associated
      with increases over time in symptoms and decreases over time in PEFR as pollution
      levels decreased. CONCLUSIONS: The physical and social environments interacted in
      predicting both biologic and clinical outcomes in children with asthma,
      suggesting that when pollution exposure is more modest, vulnerability to asthma
      exacerbations may be heightened in children with higher chronic stress.

PMID- 18629322
TI  - Breast-feeding protects against arsenic exposure in Bangladeshi infants.
AB  - BACKGROUND: Chronic arsenic exposure causes a wide range of health effects, but
      little is known about critical windows of exposure. Arsenic readily crosses the
      placenta, but the few available data on postnatal exposure to arsenic via breast
      milk are not conclusive. AIM: Our goal was to assess the arsenic exposure through
      breast milk in Bangladeshi infants, living in an area with high prevalence of
      arsenic-rich tube-well water. METHODS: We analyzed metabolites of inorganic
      arsenic in breast milk and infant urine at 3 months of age and compared them with
      detailed information on breast-feeding practices and maternal arsenic exposure,
      as measured by concentrations in blood, urine, and saliva. RESULTS: Arsenic
      concentrations in breast-milk samples were low (median, 1 microg/kg; range, 0.25
      19 microg/kg), despite high arsenic exposures via drinking water (10-1,100
      microg/L in urine and 2-40 microg/L in red blood cells). Accordingly, the arsenic
      concentrations in urine of infants whose mothers reported exclusive breast
      feeding were low (median, 1.1 microg/L; range, 0.3-29 microg/L), whereas
      concentrations for those whose mothers reported partial breast-feeding ranged
      from 0.4 to 1,520 microg/L (median 1.9 microg/L). The major part of arsenic in
      milk was inorganic. Still, the infants had a high fraction (median, 87%) of the
      dimethylated arsenic metabolite in urine. Arsenic in breast milk was associated
      with arsenic in maternal blood, urine, and saliva. CONCLUSION: Very little
      arsenic is excreted in breast milk, even in women with high exposure from
      drinking water. Thus, exclusive breast-feeding protects the infant from exposure
      to arsenic.

PMID- 18629324
TI  - Association of blood lead levels with onset of puberty in Russian boys.
AB  - BACKGROUND: Epidemiologic studies suggest a temporal trend of earlier onset and
      longer duration of puberty, raising concerns regarding the potential impact of
      environmental factors on pubertal development. Lead exposure has been associated
      with delayed pubertal onset in girls; however, epidemiologic data in boys are
      limited. METHODS: We used multivariable logistic regression models to explore the
      cross-sectional association of blood lead levels with growth and pubertal onset
      based on physician-assessed testicular volume (TV) and pubertal staging in 489
      boys 8-9 years of age from Chapaevsk, Russia. We used multivariable linear
      regression models to assess associations of blood lead levels with somatic growth
      at the study entry visit. RESULTS: The median (25th-75th percentile) blood lead
      level was 3 microg/dL (2-5 microg/dL). Height, weight, body mass index, birth
      weight, and gestational age were predictive of the onset of puberty as assessed
      either by TV (> 3 mL), genitalia stage (G2), or both. Blood lead level was
      inversely associated with height (p < 0.001) and weight (p = 0.06) after
      adjustment for birth weight, gestational age, and age at examination. In
      multivariable adjusted analyses, boys with blood lead levels > or = 5 microg/dL
      had 43% reduced odds of having entered G2 compared with those with lower levels
      (odds ratio = 0.57; 95% confidence interval, 0.34-0.95, p = 0.03). CONCLUSIONS:
      Relatively low environmental blood lead levels were associated with decreased
      growth and differences in pubertal onset in periadolescent Russian boys. Future
      analyses of this prospective cohort will address pubertal onset and progression
      in relation to lead and other environmental chemicals.

PMID- 18629325
TI  - Reduction of elevated blood lead levels in children in North Carolina and
      Vermont, 1996-1999.
AB  - BACKGROUND: Few studies have examined factors related to the time required for
      children's blood lead levels (BLLs) > or = 10 microg/dL to decline to < 10
      microg/dL. OBJECTIVES: We used routinely collected surveillance data to determine
      the length of time and risk factors associated with reducing elevated BLLs in
      children below the level of concern of 10 microg/dL. METHODS: From the North
      Carolina and Vermont state surveillance databases, we identified a retrospective
      cohort of 996 children < 6 years of age whose first two blood lead tests produced
      levels > or = 10 microg/dL during 1996-1999. Data were stratified into five
      categories of qualifying BLLs and analyzed using Cox regression. Survival curves
      were used to describe the time until BLLs declined below the level of concern. We
      compared three different analytic methods to account for children lost to follow
      up. RESULTS: On average, it required slightly more than 1 year (382 days) for a
      child's BLL to decline to < 10 microg/dL, with the highest BLLs taking even
      longer. The BLLs of black children [hazard ratio (HR) = 0.84; 95% confidence
      interval (CI), 0.71-0.99], males (HR(male) = 0.83; 95% CI, 0.71-0.98), and
      children from rural areas (HR(rural) = 0.83; 95% CI, 0.70-0.97) took longer to
      fall below 10 microg/dL than those of other children, after controlling for
      qualifying BLL and other covariates. Sensitivity analysis demonstrated that
      including censored children estimated a longer time for BLL reduction than when
      using linear interpolation or when excluding censored children. CONCLUSION:
      Children with high confirmatory BLLs, black children, males, and children from
      rural areas may need additional attention during case management to expedite
      their BLL reduction time to < 10 microg/dL. Analytic methods that do not account
      for loss to follow-up may underestimate the time it takes for BLLs to fall below
      the recommended target level.

PMID- 18629326
TI  - Time for a change: from exposure assessment to exposure science.

PMID- 18629328
TI  - Reassessing the risks of Tamiflu use during a pandemic to the Lower Colorado
      River.

PMID- 18629329
TI  - Salt mist is the right seasoning for ozone.

PMID- 18629330
TI  - Turn up the heat for respiratory health.

PMID- 18629331
TI  - In hot water: global warming takes a toll on coral reefs.

PMID- 18629332
TI  - Ozone nation: EPA standard panned by the people.

PMID- 18629333
TI  - How to control for gestational age in studies involving environmental effects on
      fetal growth.

PMID- 18629335
TI  - Incidence of new onset asthma after the World Trade Center disaster.

PMID- 18629336
TI  - Urinary mercury levels in children with amalgam fillings.

PMID- 18629337
TI  - Canyons up the pollution ante.

PMID- 18629339
TI  - Not immune to PFOS effects?

PMID- 18629341
TI  - Shining a light on BP-3 exposure.

PMID- 18629342
TI  - Is arsenic "lactation intolerant"?

PMID- 18629343
TI  - New window into breast cancer risk.

PMID- 18629344
TI  - Mischief makers.

PMID- 18629345
TI  - Sequences, annotation and single nucleotide polymorphism of the major
      histocompatibility complex in the domestic cat.
AB  - Two sequences of major histocompatibility complex (MHC) regions in the domestic
      cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break
      (55-80 MYA) and followed by a chromosomal inversion were annotated in detail.
      Gene annotation of this MHC was completed and identified 183 possible coding
      regions, 147 human homologues, possible functional genes and 36
      pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs.
      The first region spans 2.976 Mbp sequence, which encodes six classical class II
      antigens (three DRA and three DRB antigens) lacking the functional DP, DQ
      regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and
      LMP2/LMP7,TAP1/TAP2), 52 class III genes, nineteen class I genes/gene fragments
      (FLAI-A to FLAI-S). Three class I genes (FLAI-H, I-K, I-E) may encode functional
      classical class I antigens based on deduced amino acid sequence and promoter
      structure. The second region spans 0.362 Mbp sequence encoding no class I genes
      and 18 cross-species conserved genes, excluding class I, II and their
      functionally related/associated genes, namely framework genes, including three
      olfactory receptor genes. One previously identified feline endogenous retrovirus,
      a baboon retrovirus derived sequence (ECE1) and two new endogenous retrovirus
      sequences, similar to brown bat endogenous retrovirus (FERVmlu1, FERVmlu2) were
      found within a 140 Kbp interval in the middle of class I region. MHC SNPs were
      examined based on comparisons of this BAC sequence and MHC homozygous 1.9x WGS
      sequences and found that 11,654 SNPs in 2.84 Mbp (0.00411 SNP per bp), which is
      2.4 times higher rate than average heterozygous region in the WGS (0.0017 SNP per
      bp genome), and slightly higher than the SNP rate observed in human MHC (0.00337
      SNP per bp).

PMID- 18629347
TI  - Population intervention models in causal inference.
AB  - We propose a new causal parameter, which is a natural extension of existing
      approaches to causal inference such as marginal structural models. Modelling
      approaches are proposed for the difference between a treatment-specific
      counterfactual population distribution and the actual population distribution of
      an outcome in the target population of interest. Relevant parameters describe the
      effect of a hypothetical intervention on such a population and therefore we refer
      to these models as population intervention models. We focus on intervention
      models estimating the effect of an intervention in terms of a difference and
      ratio of means, called risk difference and relative risk if the outcome is
      binary. We provide a class of inverse-probability-of-treatment-weighted and
      doubly-robust estimators of the causal parameters in these models. The finite
      sample performance of these new estimators is explored in a simulation study.

PMID- 18629346
TI  - Correlated Rayleigh Scattering Spectroscopy and Scanning Electron Microscopy
      Studies of Au-Ag Bimetallic Nanoboxes and Nanocages.
AB  - The optical properties of hollow nanoparticles (Au-Ag nanoboxes and nanocages)
      were investigated by recording Rayleigh scattering spectra of single particles,
      whose morphology and composition had been analyzed by scanning electron
      microscopy (SEM). This was achieved by depositing the particles on optically
      transparent substrates with registration marks, which are compatible with SEM
      imaging. Fitting the experimental spectra to a Lorentzian function yields the
      frequencies and homogeneous line widths of the plasmon resonance for the
      particles. The resonances are extremely broad, with dephasing times of 2-5 fs.
      Analysis of the line width data using the dimensions determined by SEM shows that
      the broadening is due to a combination of electron-surface scattering and
      radiation damping. The sensitivity of the plasmon resonance to the dielectric
      constant of the environment was also investigated by adding a drop of water to
      the substrate. The nanoboxes show similar dielectric sensitivities compared to
      other metal nanoparticle systems. A significant increase in the line width was
      also observed for the nanoboxes in water compared with air. This was attributed
      to increased radiation damping in the environment with a higher dielectric
      constant. Both the red shift and the increase in line width are reversible.

PMID- 18629349
TI  - Current role of endovascular therapy in Marfan patients with previous aortic
      surgery.
AB  - The Marfan syndrome is a heritable disorder of the connective tissue which
      affects the cardiovascular, ocular, and skeletal system. The cardiovascular
      manifestation with aortic root dilatation, aortic valve regurgitation, and aortic
      dissection has a prevalence of 60% to 90% and determines the premature death of
      these patients. Thirty-four percent of the patients with Marfan syndrome will
      have serious cardiovascular complications requiring surgery in the first 10 years
      after diagnosis. Before aortic surgery became available, the majority of the
      patients died by the age of 32 years. Introduction in the aortic surgery
      techniques caused an increase of the 10 year survival rate up to 97%. The purpose
      of this article is to give an overview about the feasibility and outcome of stent
      graft placement in the descending thoracic aorta in Marfan patients with previous
      aortic surgery.

PMID- 18629350
TI  - Adherence treatment factors in hypertensive African American women.
AB  - BACKGROUND: Hypertension among African American women is of epidemic proportions.
      Nonadherence to treatment contributes to uncontrolled blood pressure in this
      population. Factors associated with adherence to treatment in African American
      women are unknown. The purpose of this study was to identify factors associated
      with adherence to hypertension treatment in African American women. METHODS: Five
      audio-taped focus groups were conducted with hypertensive African American women,
      35 years and older receiving treatment for hypertension from an inner-city free
      clinic. All transcripts from the tapes were analyzed for content describing
      adherence to treatment factors. FINDINGS: factors associated with adherence to
      treatment in hypertensive african american women were in three main categories
      including: beliefs about hypertension, facilitators of adherence to treatment,
      and barriers to adherence to treatment. IMPLICATIONS: The study supports the need
      for education on managing hypertension and medication side effects, early
      screening for depression in hypertensive African Americans, development of
      culturally sensitive hypertension educational material, and formation of support
      groups for promoting adherence to treatment among African American women with
      hypertension.

PMID- 18629351
TI  - Therapeutic implications of transesophageal echocardiography after transthoracic
      echocardiography on acute stroke patients.
AB  - BACKGROUND: The role of transesophageal echocardiography (TEE) in the evaluation
      of acute stroke patients is still ill-defined. We conducted a prospective
      observational study to find the prevalence of TEE findings that indicate
      anticoagulation as beneficial, in acute ischemic stroke patients without
      indication for anticoagulation based on clinical, electrocardiographic and
      transthoracic echocardiography (TTE) findings. METHODS: We prospectively studied
      all patients referred to our laboratory for TTE and TEE. Patients were excluded
      if the diagnosis was not acute ischemic stroke or if they had an indication for
      anticoagulation based on clinical, electrocardiographic, or TTE data. Patients
      with TEE findings that might indicate anticoagulation as beneficial were
      identified. RESULTS: A total of 84 patients with acute ischemic stroke and
      without indication for anticoagulation based on clinical and electrocardiographic
      or TTE data were included in the study. Findings indicating anticoagulation as
      beneficial were found in 32.1%: spontaneous echo contrast (1.2%), complex aortic
      atheroma (27.4%), thrombus (8.3%), and simultaneous patent foramen ovale and
      atrial septal aneurysm (2.4%). CONCLUSIONS: The results of our study show that
      TEE can have therapy implications in 32.1% of ischemic stroke patients in sinus
      rhythm and with TTE with no indication for anticoagulation.

PMID- 18629352
TI  - Androgen therapy and atherosclerotic cardiovascular disease.
AB  - Cardiovascular disease (CVD) remains the leading cause of death in Western
      society today. There is a striking gender difference in CVD with men predisposed
      to earlier onset and more severe disease. Following the recent reevaluation and
      ongoing debate regarding the estrogen protection hypothesis, and given that
      androgen use and abuse is increasing in our society, the alternate view that
      androgens may promote CVD in men is assuming increasing importance. Whether
      androgens adversely affect CVD in either men or women remains a contentious issue
      within both the cardiovascular and endocrinological fraternities. This review
      draws from basic science, animal and clinical studies to outline our current
      understanding regarding androgen effects on atherosclerosis, the major CVD, and
      asks where future directions of atherosclerosis-related androgen research may
      lie.

PMID- 18629354
TI  - Kaposiform hemangioendothelioma with distant lymphangiomatosis without an
      association to Kasabach-Merritt-Syndrome in a female adult!
AB  - Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor
      which usually occurs in infants. Clinically it appears as ill-defined red to
      purple indurated plaque. KHE is commonly associated with Kasabach-Merritt
      syndrome (KMS) and lymphangiomatosis. Microscopically, the tumor is composed of
      infiltrating lobulated nodules with slitlike or crescentic vessels which are
      poorly canalized and lined by spindle shaped endothelial cells. We report a 36
      year old female who developed a reddish tumor on the chest. Histological
      examination revealed a KHE, which was clinically not associated with
      thrombocytopenia or bleeding complications, but lymphangiomatosis at the right
      submandibular region. The association of KHE in a female adult with lymphangioma
      rather than KMS in this case supports the hypothesis that such an association may
      represent a benign subform of this disease in an adult and excision seems to be
      curative.

PMID- 18629355
TI  - Prevalence and component analysis of metabolic syndrome: an Indian
      atherosclerosis research study perspective.
AB  - Asian Indians have a high predisposition to metabolic syndrome (MS) and coronary
      artery disease (CAD). The present study aimed to estimate MS prevalence in 531
      Asian Indian families comprising of 2318 individuals. Anthropometrics and lipid
      profile were assessed. MS prevalence was estimated using standard Adult Treatment
      Panel III (ATP-III) and World Health Organisation (WHO) criteria and modified
      definitions which included lowered cut-offs for waist circumference (WC) (> or
      =90 cm for men and > or =80 cm for women], body mass index (BMI) (> or =23 kg/m2)
      and impaired fasting glucose (IFG) levels. ATP-III criteria identified a
      significantly higher proportion of people with MS (N = 933; 40.3%) compared with
      WHO (N = 708; 30.6%; p < 0.0001) while modified ATP-III showed maximum gain in
      percent prevalence among the revised criteria (17.3%; p = 0.0056). The IDF
      criteria identified similar proportion of subjects with MS (N = 809; 34.9%) as
      the revised WHO criteria (N = 792; 34.2%). The number of MS subjects was highest
      in the 50-59 years age group. MS was diagnosed a decade earlier in unaffected
      subjects compared with those with CAD/diabetes using the modified MS criteria. WC
      correlated significantly with BMI and waist-hip ratio (WHR) (p = 0.000). Among MS
      components, high density lipoprotein cholesterol and BMI contributed
      significantly in males (71.4% and 85.9%) and females (86.8% and 88.8%),
      respectively. The higher percentage contribution of WC among males and WHR among
      females indicates the influence of gynecoid/android pelvis on WHR measures. In
      conclusion, the revision of definition criteria for MS with lowered cut-offs for
      WC and BMI is critical for the accurate assessment of MS among Asian Indians.

PMID- 18629353
TI  - Endothelial effects of antihypertensive treatment: focus on irbesartan.
AB  - The endothelium is characterized by a wide range of important homeostatic
      functions. It participates in the control of hemostasis, blood coagulation and
      fibrinolysis, platelet and leukocyte interactions with the vessel wall,
      regulation of vascular tone, and of blood pressure. Many crucial vasoactive
      endogenous compounds are produced by the endothelial cells to control the
      functions of vascular smooth muscle cells and of circulating blood cells. These
      complex systems determine a fine equilibrium which regulates the vascular tone.
      Impairments in endothelium-dependent vasodilation lead to the so called
      endothelial dysfunction. Endothelial dysfunction is then characterized by
      unbalanced concentrations of vasodilating and vasoconstricting factors, the most
      important being represented by nitric oxide (NO) and angiotensin II (AT II). High
      angiotensin-converting enzyme (ACE) activity leads to increased AT II generation,
      reduced NO levels with subsequent vasoconstriction. The net acute effect results
      in contraction of vascular smooth muscle cells and reduced lumen diameter.
      Furthermore, when increased ACE activity is chronically sustained, increase in
      growth, proliferation and differentiation of the vascular smooth muscle cells
      takes place; at the same time, a decrease in the anti-proliferative action by NO,
      a decrease in fibinolysis and an increase in platelets aggregation may be
      observed. AT II is then involved not only in the regulation of blood pressure,
      but also in vascular inflammation, permeability, smooth muscle cells remodelling,
      and oxidative stress which in turn lead to atherosclerosis and increased
      cardiovascular risk. Given the pivotal role exerted by AT II in contributing to
      alteration of endothelial function, treatment with ACE inhibitors or angiotensin
      receptor blockers (ARBs) may be of particular interest to restore a physiological
      activity of endothelial cells. In this view, the blockade of the renin
      angiotensin system (RAS), has been shown to positively affect the endothelial
      function, beyond the antihypertensive action displayed by these compounds. In
      this review, attention has been specifically focused on an ARB, irbesartan, to
      examine its effects on endothelial function.

PMID- 18629356
TI  - Update on the use of fibrates: focus on bezafibrate.
AB  - Low-density lipoprotein-cholesterol (LDL-C) is a well established coronary heart
      disease (CHD) risk factor. However, the ability of this metabolic risk factor
      alone to identify individuals at rigk for future CHD events is limited. The
      raised triglycerides-low high-density lipoprotein-cholesterol (HDL-C)
      dyslipidaemia was shown to be an important cardiovascular risk factor
      independently of LDL-C levels. Fibric acid derivatives (fibrates) have been used
      in clinical practice for more than 2 decades as a class of agents known to
      decrease triglyceride levels while substantially increasing HDL-C levels. Through
      peroxisome proliferator-activated alpha-receptors, fibrates have a significant
      impact on the synthesis of several apolipoproteins and enzymes of lipoprotein
      metabolism as well as on the expression of several genes involved in fibrinolysis
      and inflammation. Data from recent primary and secondary prevention clinical
      trials demonstrate the efficacy of fibrate therapy in patients with the raised
      triglycerides-low HDL-C dyslipidaemia. This review summarizes current data
      regarding mechanism of action and the metbolic effects of fibrates, as well as
      results from major clinical trials on the efficacy of this mode of lipid lowering
      therapy. In addition, recent data from subgroup analyses of the Bezafibrate
      Infarction Prevention trial, demonstrating several important metabolic and long
      term cardiovascular effects of bezafibrate therapy, are detailed.

PMID- 18629358
TI  - Dissection of the ascending thoracic aorta as a complication of percutaneous
      coronary intervention.
AB  - Acute aortic dissection is a medical emergency with high morbidity and mortality
      requiring emergent diagnosis and therapy. A 79-year-old woman with acute aortic
      dissection due to percutaneous coronary intervention was presented. Aortic
      dissection is an uncommon but potentially lethal illness that can present in an
      occult manner making the initial diagnosis difficult. Aggressive medical
      management is mandatory, as well as urgent diagnostic testing and cardiothoracic
      consultation.

PMID- 18629357
TI  - Prediction of calculated future cardiovascular disease by monocyte count in an
      asymptomatic population.
AB  - INTRODUCTION: Although atherogenesis is clearly entwined with systemic
      inflammation, the risk-predictive relationship between preclinical and overt
      cardiovascular disease (CVD) and systemic white blood cell (WBC) subtypes remains
      unclear. Implication of an association would greatly facilitate cardiac risk
      prediction, assessment and monitoring. METHODS: 1383 asymptomatic individuals
      (795 men, 588 women) attending for executive health screening were examined
      clinically as well as with phlebotomy and exercise stress testing to determine
      their ten-year risk of developing overt cardiovascular disease (as estimated by
      both Framingham and SCORE calculations). The significance of their association
      with overall WBC and subtypes were determined using both univariate and multiple
      regression modeling. RESULTS: OF ALL WBC SUBTYPES, MONOCYTE COUNT WAS FOUND TO
      HAVE THE STRONGEST, INDEPENDENT RELATIONSHIP WITH OVERALL CVD RISK BY BACKWARDS
      LINEAR REGRESSION MODELING (FRAMINGHAM: beta = 0.057; p = 0.03; SCORE: beta =
      0.128; p = <0.0005). Independent associations with BMI (beta = 5.214; p =
      <0.0005), waist circumference (beta = 21.866; p = <0.0005), systolic blood
      pressure (beta = 10.738; p = 0.003), HDL cholesterol (beta = -0.639; p = <0.0005)
      and triglyceride concentrations (beta = 0.787; p = <0.0005) were also evident.
      Overall WBC along with neutrophils, lymphocytes and basophil subfractions were
      variably (but less strongly) associated with such dependents and outcome
      measures. CONCLUSIONS: In conclusion, monocyte count, a simple inexpensive test,
      may provide useful predictive cardiovascular risk information in asymptomatic
      individuals to inform and guide attempts at interrupting CVD development at a
      preclinical stage.

PMID- 18629359
TI  - Perioperative use of statins in noncardiac surgery.
AB  - BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)
      can significantly decrease cardiovascular mortality and morbidity, irrespective
      of the patients' cholesterol status. This paper reviews the effects of
      perioperative statin therapy in patients undergoing noncardiac surgery. METHOD: A
      systematic literature review was undertaken of all published literature on this
      subject using Medline and cross-referenced. All published relevant papers on the
      perioperative use of statins were used. RESULTS: Perioperative statin therapy is
      associated with a lower perioperative morbidity and mortality in patients
      undergoing elective or emergency surgery. The effects are due to a combination of
      lipid-lowering and pleiotropic properties of statins. CONCLUSION: Ideally a large
      scale multi-centre randomized controlled trial of perioperative statin therapy
      should be performed but this may be difficult to conduct since there is already
      overwhelming evidence in the literature to suggest perioperative cardiovascular
      protective properties. Statins may still be under-prescribed in surgical
      patients.

PMID- 18629360
TI  - Angiotensin II receptor blockers and cardiovascular protection: focus on left
      ventricular hypertrophy regression and atrial fibrillation prevention.
AB  - Left ventricular hypertrophy (LVH) and atrial fibrillation (AF) are strong
      predictors of cardiovascular (CV) morbidity and mortality, independently of blood
      pressure levels and other modifiable and nonmodifiable risk factors. The actions
      of circulating and tissue angiotensin II, mediated by AT1 receptors, play an
      important role in the development of a wide spectrum of cardiovascular
      alterations, including LVH, atrial enlargement and AF. Growing experimental and
      clinical evidence suggests that antihypertensive drugs may exert different
      effects on LVH regression and new onset AF in the setting of arterial
      hypertension. Since a number of large and adequately designed studies have found
      angiotensin II receptor blockers (ARBs) to be more effective in reducing LVH than
      beta-blockers and data are also available showing their effectiveness in
      preventing new or recurrent AF, it is reasonable to consider this class of drugs
      among first line therapies in patients with hypertension and LVH (a very high
      risk phenotype predisposing to AF) and as adjunctive therapy to antiarrhythmic
      agents in patients undergoing pharmacological or electrical cardioversion of AF.

PMID- 18629361
TI  - Next-generation drug-eluting stents in coronary artery disease: focus on
      everolimus-eluting stent (Xience V).
AB  - Percutaneous coronary revascularization has been a mainstay in the management of
      coronary artery disease since its introduction in the late 1970s. Bare-metal
      stents and, more recently, first-generation drug-eluting stents (DES), such as
      sirolimus-eluting (Cypher) and paclitaxel-eluting stents (Taxus), have further
      improved results of percutaneous coronary intervention (PCI) by improving early
      results and reducing the risk of restenosis. There is currently debate on the
      safety of these first-generation DES, given the potential for late stent
      thrombosis, especially after discontinuation of dual antiplatelet therapy. There
      are well known caveats on the performance of their respective metallic stent
      platforms, delivery, and dilation systems, and polymer coatings. Second
      generation DES, such as zotarolimus-eluting (Endeavor) and everolimus-eluting
      stents (Xience V), have recently become available in the USA and/or Europe. The
      Xience V stent holds the promise of superior anti-restenotic efficacy as well as
      long-term safety. In addition, this stent is based on the Multi-link platform and
      delivery system. Recently available data already suggest the superiority of the
      Xience V stent in comparison to the Taxus stent in terms of prevention of
      restenosis, without significant untoward events. Nonetheless, the number of
      patients studied and the follow-up duration are still too limited to enable
      definitive conclusions. Only indirect meta-analyses can be used to date to
      compare the Xience V with the Cypher. This systematic review tries to provide a
      concise and critical appraisal of the data in support of the Xience V everolimus
      eluting stent.

PMID- 18629362
TI  - Diagnosis and surgical approach of popliteal artery entrapment syndrome: a
      retrospective study.
AB  - BACKGROUND: Popliteal artery entrapment syndrome (PAES) is a rare but potentially
      limb threatening peripheral vascular disease occurring predominantly in young
      adults. This study is a retrospective review of 49 limbs in 38 patients with PAES
      treated surgically over an 8-year period. PATIENTS AND METHODS: From 1995 to
      2002, 38 patients with a mean age of 21 years (range, 18-29 years) underwent
      surgery for PAES at a single institution. The patients' demographic data and
      clinical features are recorded. The preoperative diagnosis of PAES was made based
      on various combinations of investigations including positional stress test,
      duplex ultrasonography, computed tomography, computed tomographic angiography,
      and angiography. RESULTS: Nine, 33, and 7 patients had Delaney's type I, II, and
      III PAES respectively. The surgical procedures consisted of simple release of the
      popliteal artery in 33 limbs (67.3%), autogenous saphenous vein (ASV) patch
      angioplasty with or without thromboendarterectomy (TEA) in 5 limbs (10.2%) and
      ASV graft interposition or bypass in 11 limbs (22.5%). At a median follow up of
      34 months (range, 8-42 months), there were no postoperative complications and all
      the patients were cured of their symptoms. CONCLUSIONS: PAES is an unusual but
      important cause of peripheral vascular insufficiency especially in young
      patients. Early diagnosis through a combined approach is necessary for exact
      diagnosis. Popliteal artery release alone or with vein bypass is the treatment of
      choice when intervention is indicated for good operative outcome and to prevent
      limb loss.

PMID- 18629363
TI  - Immediate and six months clinical and angiographic results of intracoronary
      paclitaxel-coated stent implantation - the Meo:DrugStar-1 study.
AB  - The study was conducted to evaluate the clinical and angiographic results of the
      implantation of the paclitaxel-eluting stent Meo:DrugStar ST in patients with
      symptomatic coronary artery disease. The Meo:DrugStar ST stent has a stainless
      steel stent platform with a homogenous non-biodegradable coating of paclitaxel
      mixed with a polyether-based biostable, monophase, and hemocompatible coating.
      Sixty patients with native coronary artery disease were included in the study.
      The Meo:DrugStar ST stents were implanted in 60 de novo lesions detected in these
      patients. Immediate and long-term clinical and angiographic follow-up results
      were evaluated. There was a high proportion of patients with hypertension (55%)
      according to JNC-VII. Mean stenosis ratio was 78 +/- 13 %, mean implanted stent
      diameter was 3.0 +/- 0.4 mm and mean length was 22 +/- 5 mm. Restenosis was
      detected in 4 (10%) of those patients and 11 (27.5%) of 40 patients had
      insignificant amount of restenosis. The results of this study indicate a
      potential benefit of the Meo:DrugStar ST stent for the prevention of stent
      thrombosis and restenosis in these relatively high-risk patients.

PMID- 18629366
TI  - Correlation of microalbumin and sialic acid with anthropometric variables in type
      2 diabetic patients with and without nephropathy.
AB  - AIM: The objective of this study is to correlate microalbumin and sialic acid
      levels with anthropometric variables in type 2 diabetic patients with and without
      nephropathy. METHODS: This study was a case control study and included 108
      Trinidadian subjects (aged 15-60 years) of which 30 were healthy individuals, 38
      had type 2 diabetes, and 40 were of type 2 diabetic patients with nephropathy.
      Blood pressure and waist to hip ratio were recorded. Fasting venous blood samples
      and urine samples were collected from all the subjects. Blood samples were
      analysed for the glucose, C-reactive protein, and sialic acid. Urine sample was
      analysed for microalbumin and sialic acid. RESULTS: Urinary microalbumin was
      higher among diabetic subjects (28.9 +/- 30.3 mg/L) compared with controls (8.4
      +/- 10.2 mg/L) and was significantly higher in diabetic patients with nephropathy
      (792.3 +/- 803.9 mg/L). Serum sialic acid was higher in subjects with diabetic
      nephropathy (71.5 +/- 23.3 mg/dL) compared to diabetics (66.0 +/- 11.7 mg/dL) and
      controls (55.2 +/- 8.3 mg/dL). Increased microalbumin and sialic acid were
      correlated with other cardiovascular risk factors such as hypertension and waist
      to hip ratios (p < 0.05). CONCLUSIONS: From these results it can be concluded
      that the increased microalbumin and sialic acid were strongly correlated with
      hypertension and waist to hip ratios in Trinidadian type-2 diabetic patients.
      Measurement of sialic acid, microalbumin, and waist to hip ratio along with the
      blood pressure is recommended for all type 2 diabetic patients to reduce the
      cardiovascular risk.

PMID- 18629365
TI  - Endoplasmic reticulum stress and diabetic retinopathy.
AB  - Endoplasmic reticulum (ER) stress is involved in the pathogenesis of several
      diseases including Alzheimer disease and Parkinson disease. Many recent studies
      have shown that ER stress is related to the pathogenesis of diabetes mellitus,
      and with the death of pancreatic beta-cells, insulin resistance, and the death of
      the vascular cells in the retina. Diabetic retinopathy is a major complication of
      diabetes and results in death of both neural and vascular cells. Because the
      death of the neurons directly affects visual function, the precise mechanism
      causing the death of neurons in early diabetic retinopathy must be determined.
      The ideal therapy for preventing the onset and the progression of diabetic
      retinopathy would be to treat the factors involved with both the vascular and
      neuronal abnormalities in diabetic retinopathy. In this review, we present
      evidence that ER stress is involved in the death of both retinal neurons and
      vascular cells in diabetic eyes, and thus reducing or blocking ER stress may be a
      potential therapy for preventing the onset and the progression of diabetic
      retinopathy.

PMID- 18629364
TI  - Implications of the obesity epidemic for lipid-lowering therapy: non-HDL
      cholesterol should replace LDL cholesterol as the primary therapeutic target.
AB  - Obesity, metabolic syndrome and diabetes are conditions with increasing
      prevalence around the world. Cardiovascular risk in diabetics is often so high as
      to overlap with event rates observed in those with established coronary disease
      and this has lead to diabetes being classified as a coronary risk equivalent.
      However, despite the elevated risk of cardiovascular events associated with
      diabetes and the metabolic syndrome, these patients often have normal low density
      lipoprotein (LDL) cholesterol despite frequent increases in apolipoprotein B,
      triglycerides and nonhigh density lipoprotein (HDL) cholesterol. In contrast to
      LDL cholesterol, non-HDL cholesterol represents cardiovascular risk across all
      patient populations but is currently only recommended as a secondary target of
      therapy by the ATP III report for patients with hypertriglyceridemia. This
      article provides an overview of the studies that shown non-HDL cholesterol to be
      superior to LDL cholesterol in predicting cardiovascular events and presents the
      case for non-HDL cholesterol being the more appropriate primary target of therapy
      in the context of the obesity pandemic. Adopting non-HDL cholesterol as the
      primary therapeutic target for all patients will conceivably lead to an
      appropriate intensification of therapy for high risk patients with low LDL
      cholesterol.

PMID- 18629367
TI  - Gadofosveset-enhanced magnetic resonance angiography.
AB  - Gadofosveset (Vasovist, Bayer Schering Pharma AG, Berlin/Germany) is the first
      intravascular contrast agent approved for use with magnetic resonance angiography
      in the European Union, Switzerland, Turkey, Canada, and Australia. Gadofosveset
      reversibly binds to albumin providing extended intravascular enhancement compared
      wth existing extracellular magnetic resonance contrast agents. Prior to approval,
      gadofosveset underwent extensive testing to evaluate the safety and efficacy of
      the drug; the clinical trials show that gadofosveset-enhanced magnetic resonance
      angiography (MRA) is safe and well tolerated in patients with vascular disease
      and effective for the detection of vascular stenosis and aneurysms gadofosveset
      has the potential to open new horizons in diagnostic MRA by increasing the
      spatial resolution and the robustness of MRA examinations and facilitating the
      examination of multiple vascular beds.

PMID- 18629368
TI  - Application in the STRATHE trial of a score system to compare the efficacy and
      the tolerability of different therapeutic strategies in the management of
      hypertension.
AB  - A score system integrating the evolution of efficacy and tolerability over time
      was applied to a subpopulation of the STRATHE trial, a trial performed according
      to a parallel group design, with a double-blind, random allocation to either a
      fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the
      possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n
      = 118), a sequential monotherapy approach (atenolol 50 mg, followed by losartan
      50 mg and amlodipine 5 mg if needed, n = 108), or a stepped-care strategy
      (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+
      hydrochlorothiazide 12.5 mg if needed, n = 103). The aim was to lower blood
      pressure below 140/90 mmHg within a 9-month period. The treatment could be
      adjusted after 3 and 6 months. Only patients in whom the study protocol was
      strictly applied were included in this analysis. At completion of the trial the
      total score averaged 13.1 +/- 70.5 (mean +/- SD) using the fixed-dose combination
      strategy, compared with -7.2 +/- 81.0 using the sequential monotherapy approach
      and -17.5 +/- 76.4 using the stepped-care strategy. In conclusion, the use of a
      score system allows the comparison of antihypertensive therapeutic strategies,
      taking into account at the same time efficacy and tolerability. In the STRATHE
      trial the best results were observed with the fixed-dose combination containing
      low doses of an angiotensin enzyme converting inhibitor (perindopril) and a
      diuretic (indapamide).

PMID- 18629369
TI  - Chronic heart failure in Japan: implications of the CHART studies.
AB  - The prognosis of patients with chronic heart failure (CHF) still remains poor,
      despite the recent advances in medical and surgical treatment. Furthermore, CHF
      is a major public health problem in most industrialized countries where the
      elderly population is rapidly increasing. Although the prevalence and mortality
      of CHF used to be relatively low in Japan, the disorder has been markedly
      increasing due to the rapid aging of the society and the Westernization of
      lifestyle that facilitates the development of coronary artery disease. The
      Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-1
      study was one of the largest cohorts in Japan. The study has clarified the
      characteristics and prognosis of Japanese patients with CHF, demonstrating that
      their prognosis was similarly poor compared with those in Western countries.
      However, we still need evidence for the prevention and treatment of CHF based on
      the large cohort studies or randomized treatment trials in the Japanese
      population. Since the strategy for CHF management is now changing from treatment
      to prevention, a larger-size prospective cohort, called the CHART-2 study, has
      been initiated to evaluate the risk factors of CHF in Japan. This review
      summarizes the current status of CHF studies in Japan and discusses their future
      perspectives.

PMID- 18629370
TI  - Candesartan in heart failure: assessment of reduction in mortality and morbidity
      (CHARM) and resource utilization and costs in Italy.
AB  - Chronic heart failure (HF) is a major cause of morbidity and mortality
      particularly in the elderly and a growing healthcare burden in Italy. The
      objective was to assess the cost-effectiveness of candesartan cilexetil, an
      angiotensin II type 1 receptor blocker (ARB) for the treatment of HF. A pre
      specified economic evaluation was conducted on resource utilization
      (cardiovascular drug treatment, cardiovascular and non-cardiovascular hospital
      admission, cardiovascular procedures/operations) prospectively collected
      alongside the CHARM program, a series of parallel randomized clinical trials
      comparing candesartan with placebo (standard therapy) in patients with NYHA Class
      II-IV HF: CHARM-Alternative (LVEF < or =40% patients not receiving ACE inhibitors
      because of previous intolerance); CHARM-Added (LVEF < or =40% patients currently
      receiving ACE inhibitors); or CHARM-Preserved (LVEF > or =40% patients). The
      primary outcome for the component trials was the composite of cardiovascular
      death or worsening hospital admission for HF and of the overall program all-cause
      mortality. Adjunctive treatment with candesartan in CHARM-Alternative and CHARM
      Added led to clinical benefits and to either cost-savings or a small additional
      cost, depending on the trial. The less certain clinical benefit in CHARM
      Preserved was obtained at modest extra cost. The incremental cost-effectiveness
      ratios (ICERs) were estimated to range from euro713 per life year gained for
      CHARM-Alternative to dominant for CHARM-Added and the pooled reduced LVEF trials.

PMID- 18629372
TI  - A hazardous finding of a rare anomalous left main coronary artery in a patient
      with a secundum atrial septal defect.
AB  - A 23-year-old male referred for evaluation of a "choking" sensation with exertion
      and a murmur. A transthoracic echocardiogram demonstrated right atrial and
      ventricular dilatation, right ventricular volume overload, and a large secundum
      atrial septal defect (ASD) with left to right shunt and a calculated pulmonary-to
      systemic blood flow ratio (Qp/Qs) estimated at 2.3 to 1. Cardiac catheterization
      also demonstrated evidence of the ASD with Qp/Qs of 4.6 to 1 with a significant
      step-up in oxygen saturation at the right atrial level. Additionally, an
      anomalous left main coronary artery (ALMCA) origin from the anterior right
      coronary cusp was suspected. Using 64-slice multidetector computed tomography
      coronary angiography (CCTA) the left main coronary artery was seen to arise from
      the right coronary cusp then traverse between the pulmonary trunk and the
      proximal ascending aorta before bifurcating into the left anterior descending and
      circumflex arteries that followed their normal courses distally. Based on the
      high risk nature of associated sudden death from an anomalous left main coronary
      artery (ALMCA) coursing between the aorta and the pulmonary trunk, the patient
      underwent surgical re-implantation of the ALMCA to the left coronary cusp and
      repair of the ASD. This case highlights a rare finding of a hazardous ALMCA in a
      patient with a secundum ASD and the utility of CCTA in evaluating the course of
      coronary anomalies along with other cardiac pathology.

PMID- 18629373
TI  - Effect of short-term lycopene supplementation and postprandial dyslipidemia on
      plasma antioxidants and biomarkers of endothelial health in young, healthy
      individuals.
AB  - The objective of this study was to test the hypothesis that the effect of a high
      fat meal (HFm) on plasma lipid-soluble antioxidants and biomarkers of vascular
      oxidative stress and inflammation would be attenuated by short-term lycopene
      supplementation in young healthy subjects. Following restriction of lycopene
      containing foods for 1-wk (LYr), blood was collected in a fasting state and 3 h
      after a HFm and a low-fat meal (LFm) in N = 18 men aged 23 +/- 2 years, and after
      a HFm only in N = 9 women aged 23 +/- 1 years. Blood was also sampled pre- and
      post-meals following 1-wk of 80 mg/day lycopene supplementation (LYs) under
      continued dietary LYr. In the fasting state, LYs compared with LYr not only
      evoked a >2-fold increase in plasma lycopene but also increased plasma beta
      carotene and alpha-tocopherol (p < 0.01), though LYs did not affect plasma
      nitrate/nitrite (biomarker of nitric oxide), malondialdehyde (biomarker of lipid
      oxidative stress), vascular- and intercellular-adhesion molecules or C-reactive
      protein (biomarkers of inflammation). Contrary to the hypothesis, the HFm-induced
      dyslipidemic state did not affect plasma malondialdehyde, C-reactive protein, or
      adhesion molecules in either LYr or LYs. Both the HFm and LFm were associated
      with decreases in the nitric oxide metabolites nitrate/nitrite and lipid-soluble
      antioxidants (p < 0.05). The data revealed that 1-wk of LYs increased plasma
      lycopene, beta-carotene, and alpha-tocopherol yet despite these marked changes to
      the plasma lipid-soluble antioxidant pool, biomarkers of vascular oxidative
      stress and inflammation were unaffected in the fasted state as well as during
      dyslipidemia induced by a HFm in young healthy subjects.

PMID- 18629374
TI  - Lipid-lowering effects of methanolic extract of Vernonia amygdalina leaves in
      rats fed on high cholesterol diet.
AB  - We investigated the lipid-lowering effects of methanolic extract of Vernonia
      amygdalina (VA) leaves in rats fed an high cholesterol diet, and compared with a
      standard hypolipidemic drug, Questran (Qu). The effects of VA on the lipid
      profile were assessed by measuring the levels of total cholesterol, triglyceride,
      low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)
      cholesterol, lipid peroxidation (LPO), phospholipid, and glutathione (GSH) in the
      plasma and liver of the rats. Administration of cholesterol at a dose of 30
      mg/0.3 ml, five times in a week for nine consecutive weeks resulted in a
      significant increase (p < 0.05) in plasma and post mitochondrial fraction (PMF)
      cholesterol levels by 33% and 55%, respectively. However, treatment with extract
      of VA at doses of 100 and 200 mg/kg caused a dose dependent reduction in the
      plasma and PMF cholesterol by 20%, 23% and 23%, 29%, respectively. Similar
      reduction in cholesterol levels was obtained in Qu-treated rats. Furthermore, VA
      at 200 mg/kg decreased the plasma and PMF LDL-cholesterol levels by 23% and 49%,
      and also decreased plasma and PMF triglyceride levels by 29% and 28%,
      respectively. Also, VA at 100 and 200 mg/kg caused a dose-dependent increase in
      plasma HDL-cholesterol levels by 41% and 59%, respectively. However, there were
      no significant differences (p > 0.05) in the PMF HDL-cholesterol and phospholipid
      levels of the treated rats when compared to hypercholesterolemic rats. There were
      significant decreases (p < 0.05) in the LPO levels of extract-treated rats.
      Precisely, VA at 100 and 200 mg/kg decreased the levels of plasma and PMF LPO by
      38%, 42% and 35%, 45%, respectively. In addition, VA augmented the cholesterol
      induced decrease in PMF glutathione levels of the rats. Taken together, these
      results suggest the lipid-lowering effects of VA and, probably serve as a new
      potential natural product for the treatment of hyperlipidemia.

PMID- 18629371
TI  - High density lipoprotein cholesterol: an evolving target of therapy in the
      management of cardiovascular disease.
AB  - Since the pioneering work of John Gofman in the 1950s, our understanding of high
      density lipoprotein cholesterol (HDL-C) and its relationship to coronary heart
      disease (CHD) has grown substantially. Numerous clinical trials since the
      Framingham Study in 1977 have demonstrated an inverse relationship between HDL-C
      and one's risk of developing CHD. Over the past two decades, preclinical research
      has gained further insight into the nature of HDL-C metabolism, specifically
      regarding the ability of HDL-C to promote reverse cholesterol transport (RCT).
      Recent attempts to harness HDL's ability to enhance RCT have revealed the
      complexity of HDL-C metabolism. This review provides a detailed update on HDL-C
      as an evolving therapeutic target in the management of cardiovascular disease.

PMID- 18629375
TI  - Application of cardiovascular disease risk prediction models and the relevance of
      novel biomarkers to risk stratification in Asian Indians.
AB  - The increasing pressure on health resources has led to the emergence of risk
      assessment as an essential tool in the management of cardiovascular disease
      (CVD). Concern exists regarding the validity of their generalization to all
      populations. Existing risk scoring models do not incorporate emerging 'novel'
      risk factors. In this context, the aim of the study was to examine the relevance
      of British, European, and Framingham predictive CVD risk scores to the
      asymptomatic high risk Indian population. Blood samples drawn from the
      participants were analyzed for various 'traditional' and 'novel' biomarkers, and
      their CVD risk factor profiling was also done. The Framingham model defined only
      5% of the study cohort to be at high risk, which appears to be an underestimation
      of CVD risk in this genetically predisposed population. These subjects at high
      risk had significantly elevated levels of lipid, pro-inflammatory, pro
      thrombotic, and serological markers. It is more relevant to develop risk
      predictive scores for application to the Indian population. This study
      substantiates the argument that alternative approaches to risk stratification are
      required in order to make them more adaptable and applicable to different
      populations with varying risk factor and disease patterns.

PMID- 18629376
TI  - Heart failure in sub-Saharan Africa: a literature review with emphasis on
      individuals with diabetes.
AB  - PURPOSE: Heart failure is the ultimate complication of cardiac involvements in
      diabetes. The purpose of this review was to summarize current literature on heart
      failure among people with diabetes mellitus in sub-Saharan Africa (SSA). METHOD:
      Bibliographic search of published data on heart failure and diabetes in sub
      Saharan Africa over the past 26 years. RESULTS: Heart failure remains largely
      unexplored in general population and among people with diabetes in Africa. Heart
      failure accounts for over 30% of hospital admission in specialized cardiovascular
      units and 3%-7% in general internal medicine. Over 11% of adults with heart
      failure have diabetes. Risk factors for heart failure among those with diabetes
      include classical cardiovascular risk factors, without evidence of diabetes
      distinctiveness for other predictors common in Africa. Prevention, management,
      and outcomes of heart failure are less well known; recent data suggest
      improvement in the management of risk factors in clinical settings. CONCLUSIONS:
      Diabetes mellitus is growing in SSA. Related cardiovascular diseases are emerging
      as potential health problem. Heart failure as cardiovascular complication remains
      largely unexplored. Efforts are needed through research to improve our knowledge
      of heart failure at large in Africa. Multilevel preventive measures, building on
      evidences from other parts of the world must go along side.

PMID- 18629377
TI  - Carvedilol in hypertension treatment.
AB  - Although beta-blockers have been previously shown to effectively reduce blood
      pressure (BP) and have been used for hypertension treatment for over 40 years,
      their effect on cardiovascular morbidity and mortality in hypertensive patients
      remains controversial and its use in uncomplicated hypertension is currently
      under debate. However, data on the above field derive mainly from studies which
      were conducted with older agents, such as atenolol and metoprolol, while
      considerable pharamacokinetic and pharmacodynamic heterogeneity is present within
      the class of beta-blockers. Carvedilol, a vasodilating non-cardioselective beta
      blocker, is a compound that seems to give the opportunity to the clinician to use
      a cardioprotective agent without the concerning hemodynamic and metabolic actions
      of traditional beta-blocker therapy. In contrast with conventional beta-blockers,
      carvedilol maintains cardiac output, has a less extended effect on heart rate and
      reduces BP by decreasing vascular resistance. Further, several studies has shown
      that carvedilol has a beneficial or at least neutral effect on metabolic
      parameters, such as glycemic control, insulin sensitivity, and lipid metabolism,
      suggesting that they could be used in subjects with the metabolic syndrome or
      diabetes without negative consequences. This article summarizes the distinct
      pharmacologic, hemodynamic, and metabolic properties of carvedilol in relation to
      conventional beta-blockers, attempting to examine the potential use of this agent
      for hypertension treatment.

PMID- 18629378
TI  - Sexual Risk Intervention In Multiethnic Drug And Alcohol Users.
AB  - An estimated 38.6 million persons globally are living with HIV, of whom over 1.1
      million reside in Zambia. Of the 2 million cases in the US, 64% of new cases
      among women are among African Americans. Alcohol and drug use represents a
      significant risk factor for HIV transmission among both Zambians and African
      Americans. In addition, gender dynamics in both the US and Zambia promote
      transmission. This study examines two interventions targeting HIV risk behavior
      among HIV positive substance users, women in Miami, USA (the New Opportunities
      for Women (NOW) Project) and men in Lusaka, Zambia (the Partner Project). The
      study compares the efficacy of these two culturally tailored sexual behavior
      interventions provided in group and individual session formats. US and Zambian
      participants increased sexual barrier use and reduced substance-related sexual
      risk. Comparatively greater gains were made by higher risk Zambian males than US
      females in both group and individual conditions. Among lower risk participants,
      women in the group condition achieved and sustained the greatest comparative risk
      reductions. Results suggest that cost effective group HIV transmission risk
      reduction interventions for multiethnic individuals can be successfully
      implemented among both female and male drug and alcohol users in multinational
      settings.

PMID- 18629380
TI  - Acute decompensated heart failure: an introduction.

PMID- 18629379
TI  - Proteomic analysis of skin invasion by blood fluke larvae.
AB  - BACKGROUND: During invasion of human skin by schistosome blood fluke larvae
      (cercariae), a multicellular organism breaches the epidermis, basement membrane,
      and dermal barriers of skin. To better understand the pathobiology of this
      initial event in schistosome infection, a proteome analysis of human skin was
      carried out following invasion by cercariae of Schistosoma mansoni. METHODOLOGY
      AND RESULTS: Human skin samples were exposed to cercariae for one-half hour to
      two hours. Controls were exposed to water used to collect cercariae in an
      identical manner, and punctured to simulate cercarial tunnels. Fluid from both
      control and experimental samples was analyzed by LC/MS/MS using a linear ion trap
      in "triple play" mode. The coexistence of proteins released by cercariae and host
      skin proteins from epidermis and basement membrane confirmed that cercarial
      tunnels in skin were sampled. Among the abundant proteins secreted by cercariae
      was the cercarial protease that has been implicated in degradation of host
      proteins, secreted proteins proposed to mediate immune invasion by larvae, and
      proteins implicated in protection of parasites against oxidative stress.
      Components of the schistosome surface tegument, previously identified with immune
      serum, were also released. Both lysis and apoptosis of epidermal cells took place
      during cercarial invasion of the epidermis. Components of lysed epidermal cells,
      including desmosome proteins which link cells in the stratum granulosum and
      stratum spinosum, were identified. While macrophage-derived proteins were
      present, no mast cell or lymphocyte cytokines were identified. There were,
      however, abundant immunoglobulins, complement factors, and serine protease
      inhibitors in skin. Control skin samples incubated with water for the same period
      as experimental samples ensured that invasion-related proteins and host protein
      fragments were not due to nonspecific degeneration of the skin samples.
      CONCLUSIONS: This analysis identified secreted proteins from invasive larvae that
      are released during invasion of human skin. Analysis of specific host proteins in
      skin invaded by cercariae served to highlight both the histolytic events
      facilitating cercarial invasion, and the host defenses that attempt to arrest or
      retard invasion. Proteins abundant in psoriatic skin or UV and heat-stressed skin
      were not abundant in skin invaded by cercariae, suggesting that results did not
      reflect general stress in the surgically removed skin specimen. Abundant
      immunoglobulins, complement factors, and serine protease inhibitors in skin form
      a biochemical barrier that complements the structural barrier of the epidermis,
      basement membrane, and dermis. The fragmentation of some of these host proteins
      suggests that breaching of host defenses by cercariae includes specific
      degradation of immunoglobulins and complement, and either degradation of, or
      overwhelming the host protease inhibitor repertoire.

PMID- 18629381
TI  - Acute decompensated heart failure.
AB  - Acute decompensated heart failure is the most common cause of hospitalization for
      patients older than 65 years of age. Although treatment of this condition has
      improved over the past two decades, the specific approach to patients in the
      acute setting has not evolved in the same way. A patient facing acute
      decompensation is experiencing a serious medical condition that is associated
      with a poor prognosis. In addition, acute decompensated heart failure results in
      significant costs to the health care system. Significant morbidity and mortality
      are associated with patients who are readmitted within a year of the first
      hospitalization. Because of this important problem, further research on improving
      the prognosis for this condition is warranted. The present article will focus on
      the risk factors associated with acute decompensation and the importance of this
      condition, both on prognosis and economics.

PMID- 18629382
TI  - Current treatment options for early management in acute decompensated heart
      failure.
AB  - Acute decompensated heart failure (ADHF) is a common syndrome that precedes over
      100,000 hospitalizations in Canada per year (with length of stay in excess of six
      to eight days), making this the most costly disorder for patients older than 65
      years of age. Over 85% of ADHF patients present with shortness of breath and
      exhibit evidence of volume overload. These findings may be variable in elderly
      patients, which complicates diagnosis. In fact, even in experienced centres,
      diagnostic accuracy is less than 80%. Despite advances in the treatment of
      chronic heart failure, meaningful improvements in outcomes associated with ADHF
      are very few. The basic assessment and treatments have not changed (early
      parenteral diuretics, electrocardiographic and oxygen saturation monitoring,
      supplemental oxygen administration). The introduction of measurement of
      natriuretic peptides in those in whom the diagnosis is uncertain may reduced the
      error rate by over 50%. The use of vasodilator therapy in the absence of
      cardiogenic shock can lead to earlier amelioration of symptoms, especially in
      those who do not respond to initial diuretics. Repeated monitoring of vital
      signs, body weight, electrolytes and creatinine levels is essential to minimize
      the risk of side effects of treatments. Noninvasive ventilation may reduce the
      need for endotracheal intubation in patients with severe ADHF and hypoxia at
      rest. Once the initial phase of heart failure treatment is completed, then the
      clinician should begin to focus on maximization of chronic heart failure therapy
      and discharge planning.

PMID- 18629383
TI  - Molecular and physiological effects of nesiritide.
AB  - BACKGROUND: Nesiritide (Natrecor, Janssen-Ortho Inc, Canada), or recombinant
      human B-type natriurtic peptide (BNP), is a molecule identical in structure to
      endogenous BNP-32. This peptide is secreted from cardiac myocytes in response to
      volume and pressure overload. While high levels of circulating BNP are measured
      by commercially available assays during acute decompensated heart failure (ADHF),
      the detection of alternate, potentially more active, but undermeasured forms of
      BNP needs to be considered. AIM: The present review summarizes the molecular and
      physiological effects of nesiritide in the setting of hospitalized patients with
      ADHF. In particular, an overview of the molecular structure and circulating
      isoforms of BNP is given, followed by a discussion of the vasodilatory, renal,
      antagonistic neurohormonal, pulmonary, anti-inflammatory and cardiac remodelling
      effects of recombinant human BNP. SUMMARY: Nesiritide has beneficial effects in
      the treatment of ADHF that go beyond the traditional goals of reducing pulmonary
      capillary wedge pressure, preload and afterload, and relieving symptoms of
      dyspnea. Therefore, the unique pharmacological profile of this medication
      provides an additional treatment option for Canadian patients with ADHF.

PMID- 18629384
TI  - Nesiritide: the clinical experience.
AB  - Nesiritide is an effective therapy in decreasing symptoms and left ventricular
      filling pressure in patients with acute decompensated heart failure. Health
      Canada has recently approved this agent for the management of this patient
      population. The clinical trials to date using nesiritide for the management of
      decompensated heart failure have been summarized. The clinical experience
      including indications for use, contraindications, dosage and monitoring has been
      reviewed. The following should serve as a general guide for the clinical use of
      nesiritide.

PMID- 18629385
TI  - Chronic kidney disease, heart failure and anemia.
AB  - The triad of chronic kidney disease, heart failure and anemia is well described
      and frequently encountered in clinical practice. While individually these disease
      states are associated with significant morbidity and mortality, the presence of
      the triad portends an even worse prognosis. Anemia is prevalent among cohorts of
      patients with chronic kidney disease and heart failure, indicating that its
      presence may serve as a central unifying hypothesis to explain poor outcomes in
      these populations. Observational and interventional trials of erythropoietin
      stimulating agents, however, have had variable results on cardiovascular end
      points. Data are now emerging that suggest that treating erythropoietin
      deficiency in and of itself may be as or more important than the absolute levels
      of hemoglobin attained. Future research in this arena must focus on the optimal
      dose of erythropoietin administered to hemoglobin level achieved that will result
      in improved cardiovascular outcomes for patients with heart failure and kidney
      disease.

PMID- 18629387
TI  - A Canadian context for the Acute Study of Clinical Effectiveness of Nesiritide
      and Decompensated Heart Failure (ASCEND-HF) trial.
AB  - Congestive heart failure comprises a major public health problem destined to grow
      enormously over the next decade. Paradoxically, and in contrast to acute coronary
      disease, acute heart failure has been relatively understudied. Current standards
      of care involve the use of intravenous diuretics and vasodilators; inotropic
      agents have been restricted to in-hospital use because of concern about their
      potential harmful effects. The emergence of recombinant human B-type natriuretic
      peptide (BNP) provides an interesting therapeutic alternative because of its
      capacity to promote vasodilation as well as increase salt and water excretion,
      and improve pulmonary congestion by reducing left ventricular filling pressure.
      This agent will be explored in the Acute Study of Clinical Effectiveness of
      Nesiritide and Decompensated Heart Failure (ASCEND-HF), the largest ever trial
      conducted in acute decompensated heart failure. Patients will be studied through
      day 30 with end points of all-cause mortality in rehospitalization as the primary
      composite outcome. A variety of mechanistic substudies are planned as well as an
      assessment of the health care economic implications of acute heart failure and
      the pathophysiological elements hypothesized to modulate the expected treatment
      effect examined. The trial is embedded in an academic research organization motif
      and promises to provide a significant contribution to the body of knowledge in
      acute heart failure and the care of patients so afflicted.

PMID- 18629386
TI  - Cardiorenal syndrome in heart failure: a cardiologist's perspective.
AB  - One of the most important comorbidities in heart failure is renal dysfunction.
      Diminished estimated glomerular filtration rate is a potent predictor of
      cardiovascular mortality and complications. On the other hand, worsening heart
      failure or acute decompensated heart failure can accelerate worsening of renal
      function--the so-called cardiorenal syndrome. Risk factors include hypertension,
      diabetes, elderly age, and prior history of heart or renal failure. The
      pathophysiology of the cardiorenal syndrome involves intrarenal hemodynamics,
      transrenal perfusion pressure and systemic neurohormonal factors. Clinical
      management of the patient with cardiorenal syndrome includes the challenge of
      diuretic resistance, which may involve correcting the underlying cause,
      combination diuretics or diuretic infusions. The key to improved outcome is the
      optimization of proven heart failure therapies. The use of vasodilator therapy is
      the current mainstay of treatment. Nesiritide, or recombinant B-type natriuretic
      peptide, has courted controversy regarding its role in cardiorenal syndrome.
      However, data are emerging that low doses appear to be renal-protective. Other
      more recent strategies include ultrafiltration, vasopressin antagonists and
      adenosine antagonists. All of these newer modalities promise more rapid volume
      removal, but their ultimate impact on survival or preservation of renal function
      is unknown at the present time. Because of the complex nature of these patients,
      and the compromised outcome, it is important that cardiologists, nephrologists
      and internists all work together toward the common goal of protecting the patient
      with cardiorenal syndrome, and use the best available evidence for management.

PMID- 18629388
TI  - Hepatic lesion radiotherapy: a new option? Interview by Paul Adams.

PMID- 18629389
TI  - Evaluation of lower functional gut disorders.

PMID- 18629390
TI  - Endoscopist-administered propofol: a retrospective safety study.
AB  - BACKGROUND: Propofol is an anesthetic agent that is commonly used for conscious
      sedation. Propofol has advantages as a sedative agent for endoscopic procedures
      including rapid onset, short half-life and rapid recovery time. However, concerns
      exist regarding the potential for respiratory depression, hypotension,
      perforation due to deep sedation and the need for monitoring by an anesthetist.
      Propofol has been used under endoscopist supervision at the Stanton Territorial
      Hospital in Yellowknife, Northwest Territories since 1996 (approximately 7000
      cases). METHODS: A retrospective chart review of endoscopic procedures conducted
      at the Stanton Territorial Hospital between January 1996 and May 2007 was
      performed. A random sample of 680 procedures was reviewed from a total of 6396
      procedures. RESULTS: The mean (+/- SD) baseline systolic blood pressure (SBP) was
      122.8+/-17.0 mmHg. The mean lowest SBP was 101.7+/-14.5 mmHg. The mean absolute
      drop in SBP was 21.1+/-16.7 mmHg, with a mean per cent drop of 16.3%+/-11.7%.
      Eighty-eight patients (12.9%) developed transient hypotension (SBP lower than 90
      mmHg). All patients regained normal blood pressure spontaneously on repeated
      measurement. No patients required intravenous fluid resuscitation. The mean O2
      saturation was 96.4%+/-2.1%. One patient (0.1%) transiently desaturated (O2
      saturation 89%), but recovered spontaneously on repeat measurement with no
      intervention. No procedures were aborted for patient safety. There were no major
      complications, including perforation or death. There was one mucosal tear during
      nontherapeutic colonoscopy (0.1%). CONCLUSIONS: Propofol can be safely
      administered in a community hospital setting under endoscopist supervision, with
      no additional support or monitoring.

PMID- 18629391
TI  - Wait time for endoscopic evaluation at a Canadian tertiary care centre:
      comparison with Canadian Association of Gastroenterology targets.
AB  - BACKGROUND: In recent years, there has been considerable concern regarding wait
      times for Canadian health care, which led the Canadian Association of
      Gastroenterology (CAG) to develop specific wait time targets. OBJECTIVES: To
      quantify wait times for endoscopic procedures at a tertiary care centre and
      correlate these with clinical presentation, impact on quality of life (QOL) and
      final diagnosis; and to determine how well the CAG wait time targets are being
      met. METHODS: Patients completed a 12-item questionnaire regarding wait times and
      their impact on QOL. A blind review was performed of the endoscopic results, with
      a specific focus on correlating wait time with a final diagnosis of serious and
      treatable diseases. RESULTS: The average total wait time for the 417 participants
      in the present study was 229 days; 78.6% did not meet CAG wait time targets. The
      wait time for screening colonoscopy was longer, and the proportion of patients
      meeting wait time targets was significantly smaller, than for patients referred
      with iron deficiency anemia or a positive fecal occult blood test result. The 41
      patients deemed to have a high-impact diagnosis established by endoscopy had a
      median wait time of 115 days, and only 23.5% met wait time targets. Overall,
      38.4% of patients believed that their wait was too long, 13.9% missed school or
      work in the preceding month because of gastrointestinal symptoms and 23% reported
      being very worried about having a serious disease. CONCLUSIONS: The majority of
      patients waiting for endoscopy did not meet CAG wait time targets, with the
      screening colonoscopy group faring the worst. Many of these patients await a
      definitive diagnosis of serious diseases that negatively impact QOL.

PMID- 18629392
TI  - Does subclinical malabsorption of carbohydrates prevent colorectal cancer? A
      hypothesis.
AB  - The incidence of colorectal cancer (CRC) is high in the western world and low in
      Asia and Africa. Fibre and starch are thought to be important protective factors,
      with a strong inverse relationship between starch consumption and CRC incidence.
      Whether this is true in Asia, particularly, and Africa is debatable. Because rice
      is the most easily absorbed of carbohydrates, a mechanism whereby there is an
      increased starch load in the colon in the Asian population needs to be
      identified. One possible cause is subclinical malabsorption. This is linked to
      increased mucosal permeability and low gross domestic product (GDP) per capita,
      which reflects poor sanitation and water supplies with increased risk for small
      bowel bacterial overgrowth leading to mucosal cell damage. A potential cause of
      the dramatic rise in CRC incidence in Japan may relate to its equally dramatic
      increase in GDP per capita of 600% over 50 years. This correlation appears to be
      stronger than with other dietary factors including fruit, vegetables and meat.
      Worldwide, a close correlation exists among low GDP per capita, low CRC incidence
      and presumed subclinical malabsorption. All these factors combine to maintain a
      low incidence of CRC in poorly developed countries.

PMID- 18629393
TI  - Fecal DNA screening in colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most common type of cancer diagnosed in
      Canada, and is the leading cause of cancer-related deaths in nonsmokers. Although
      CRC is considered to be 90% curable if detected early, the majority of patients
      present with advanced stage III or IV disease. An effective screening test may
      significantly decrease disease burden. The present paper examines the rationale
      and potential of fecal DNA testing as an alternative and adjunct to other CRC
      screening tests. The most efficacious fecal DNA test developed to date has a
      sensitivity and specificity of 87.5% and 82%, respectively. The approach has a
      higher positive predictive value than the currently used fecal occult blood test
      and offers a noninvasive option to patients. It is not reliant on the presence of
      bleeding, which may be intermittent or altogether absent. The test is now
      commercially available and is supported by a number of American insurers. Current
      challenges include cost reduction and demonstration of mortality benefit in a
      rigorous clinical trial. Despite current challenges, fecal DNA testing is worth
      pursuing. Both the American Gastroenterological Society and the American Cancer
      Society maintain that molecular testing is in its infancy but is promising. Fecal
      DNA testing has the potential to be an exciting addition to the current armament
      of CRC screening options.

PMID- 18629394
TI  - Colonic interposition in a woman with attenuated familial adenomatosis polyposis:
      does the location of the colon affect polyp formation?
AB  - Attenuated familial adenomatous polyposis (AFAP) is a rare but well-established
      cause of colorectal carcinoma and multiple polyps. The present paper describes a
      case of a woman diagnosed with colorectal cancer at 34 years of age and
      subsequently found to have AFAP by genetic testing. During infancy, the patient
      underwent surgical correction of esophageal atresia with colonic interposition.
      While she had developed adenomatous polyps in her native cecum, there was no
      evidence of polyps or cancer in the segment of large intestine interposed between
      her upper esophagus and stomach. Therefore, various environmental differences
      between the upper and lower gastrointestinal tract may play a role in the
      expression of AFAP phenotype.

PMID- 18629395
TI  - Colonoscopic preoperative localization using submucosal injection of
      radiolabelled colloid.
AB  - Malignant colonic polyps can be removed endoscopically but surgical resection is
      sometimes required. However, the polypectomy site can be difficult to locate.
      Current methods use various tattooing agents, with varying degrees of success. A
      new technique using preoperative injection of technetium-99m-labelled antimony
      colloid, with intraoperative localization using a handheld gamma probe, is
      described. Although unsuccessful in terms of localizing a previously partially
      resected polyp, the technique itself proved safe and simple, and has some
      advantages over other endoscopic approaches.

PMID- 18629396
TI  - Unconventional electronic and magnetic functions of nanographene-based host-guest
      systems.
AB  - Nanographene has a unique electronic structure which critically depends on the
      shape of its edge. A zigzag-edged nanographene sheet has a non-bonding pi
      electron state (edge state), yielding a strong spin magnetism for edge-state
      localized spins, in spite of the absence of such a state in an armchair-edged
      nanographene sheet. Nanographite (stacked nanographene sheets)-network-based
      nanoporous carbon is employed as the host material to build unconventional
      magnetic systems based on the host-guest interaction. The physisorption of
      various guest materials can cause a reversible low-spin/high-spin magnetic
      switching phenomenon, whose feature varies depending on the type of guest
      species. The edge-state spins are utilized as a probe to detect a huge
      condensation of helium atoms in the nanopores. The giant magnetoresistance of the
      nanographite network is controlled by the physisorption of magnetic oxygen
      molecules. The confinement of potassium clusters in the nanopores surrounded by
      nanographite domains yields an interesting nanomagnetic state.
      Nanographene/nanographite is an intriguing pi-electron-based nanocarbon material
      with the potential of producing unconventional magnetic structures that cannot be
      obtained using bulk graphite. The processability of nanographene/nanographite is
      expected to give a variety of magnetic functions for spintronic applications.

PMID- 18629397
TI  - Perspectives in paramagnetic NMR of metalloproteins.
AB  - NMR experiments and tools for the characterization of the structure and dynamics
      of paramagnetic proteins are presented here. The focus is on the importance of
      (13)C direct-detection NMR for the assignment of paramagnetic systems in
      solution, on the information contained in paramagnetic effects observed both in
      solution and in the solid state, and on novel paramagnetism-based tools for the
      investigation of conformational heterogeneity in protein-protein complexes or in
      multi-domain proteins.

PMID- 18629398
TI  - Hetero-arylboroxines: the first rational synthesis, X-ray crystallographic and
      computational analysis.
AB  - A novel series of hetero-arylboroxines were synthesized and structurally
      characterized by X-ray diffraction, NMR and computational analysis. The solid
      state structures of the hetero-arylboroxines represent the first report of AB(2)
      type hetero-arylboroxines.

PMID- 18629399
TI  - Metal-mediated thiol-disulfide interconversion--a new tool for
      metallosupramolecular chemistry.
AB  - Metal-mediated redox-interconversion of the new ligand 2,2':6',2''-terpyridine
      6(1H)-thione and the corresponding disulfide allows the programmed assembly of
      dinucleating ligands.

PMID- 18629400
TI  - The first use of the free selenimide Ph2Se=NH as a synthon; the synthesis and X
      ray crystal structure of [Ph2SeNSePh2][BPh4].
AB  - Reaction of o-mesitylsulfonylhydroxylamine (MSH) with Ph(2)Se results in the
      [Ph(2)SeNH(2)](+) cation; low temperature deprotonation (LDA), bromination (NBS)
      and then treatment with Ph(2)Se-Na[BPh(4)] generates [Ph(2)SeNSePh(2)][BPh(4)],
      via the selenimides Ph(2)Se=NH and Ph(2)Se=NBr.

PMID- 18629401
TI  - Solution studies of trimetallic lanthanide luminescent anion sensors: towards
      ratiometric sensing using an internal reference channel.
AB  - Luminescent europium and terbium complexes and a mixed Eu(III)-Tb(III) complex
      were prepared, each with three macrocycles coordinating to a single lanthanide
      ion to form a trimetallic system, and can be used for the ratiometric sensing of
      anions in the case of the mixed complex.

PMID- 18629402
TI  - Studies of nitric oxide interaction with mono- and dinuclear copper(II) complexes
      of prion protein bis-octarepeat fragments.
AB  - The interaction of nitric oxide with copper(ii) complexes of two octarepeat
      sequences belonging to the prion protein was studied, considering both
      mononuclear and dinuclear systems, i.e. Cu-Ac-(PHGGGWGQ)(2)-NH(2) and Cu(2)-Ac
      (PHGGGWGQ)(2)-NH(2), respectively. The NO interaction with both systems was
      followed in aqueous solutions at physiological pH value, by using UV-Vis and EPR
      spectroscopic techniques as well as cyclic voltammetry. The mechanism of NO
      interaction with the mononuclear copper complex can be considered similar to that
      previously observed for the analogous copper systems with Ac-HGGG-NH(2) and Ac
      PHGGGWGQ-NH(2). A more complicated behaviour was found with the copper dinuclear
      system, in which the involvement of two different intermediate complex species
      was evidenced. A positive cooperativity between the two copper ions, in the
      reduction process was inferred. When working with a large excess of the Ac
      (PHGGGWGQ)(2)-NH(2) ligand, the frozen-solution EPR parameters pertain to the
      well characterized [Cu(N(im))(4)](2+) unit, which did not exhibit any interaction
      with NO. The presence of a free coordination site is the necessary requirement
      for the NO interaction to occur, as found only in the square-pyramidal geometry
      of [Cu(L)H(-2)] or [Cu(2)(L)H(-4)] complex species, which form when copper and
      ligand concentrations are similar.

PMID- 18629403
TI  - Highly asymmetric coordination of trimethylsilyl groups to tetrazole and triazole
      rings: an experimental and computational study in gaseous and crystalline phases.
AB  - 1-Trimethylsilyltetrazole, 1, has been synthesised from chlorotrimethylsilane and
      tetrazole in the presence of triethylamine as an auxiliary base. The structure of
      this compound has been determined in the crystalline phase by X-ray diffraction
      of a crystal grown in situ. The gas-phase structures of 1 and 1-trimethylsilyl
      1,2,4-triazole, 2, have been determined by gas-phase electron diffraction (GED).
      An extensive investigation of these and related compounds by ab initio
      calculations is also reported. The angles between the rings and the substituents
      on N were of particular interest. It was found that the calculated difference of
      15.5 degrees between the CNSi and NNSi angles in 1 was mostly, but not entirely,
      an inherent property of the tetrazole ring and not due to a short SiN
      interaction.

PMID- 18629404
TI  - Construction of different dimensional inorganic-organic hybrid materials based on
      polyoxometalates and metal-organic units via changing metal ions: from non
      covalent interactions to covalent connections.
AB  - Five POM-based hybrid materials have been designed and synthesized based on
      different metal ions under hydrothermal conditions, namely,
      [Zn(Hfcz)(H(2)O)(3)](H(3)fcz)(SiMo(12)O(40)).3H(2)O (1),
      [Cd(2)(Hfcz)(6)(H(2)O)(2)](SiMo(12)O(40)).H(2)O (2),
      [Co(2)(Hfcz)(2)(SiW(12)O(40))](H(3)fcz)(2)(SiW(12)O(40)).10H(2)O (3),
      [Ni(2)(Hfcz)(4)(H(2)O)(2)](SiW(12)O(40)).5H(2)O (4) and
      [Ag(4)(Hfcz)(2)(SiMo(12)O(40))] (5), where Hfcz is fluconazole [2-(2,4
      difluorophenyl)-1,3-di(1H-1,2,4-triazol-1-yl)propan-2-ol]. Their crystal
      structures have been determined by X-ray diffraction, elemental analyses, IR
      spectra, and thermogravimetric analyses (TGA). There are 1D mono and double chain
      like metal-organic units in compounds 1 and 2, respectively. Polyoxometalates and
      metal-organic units co-crystallize through hydrogen bonds. In compound 3, metal
      organic sheets are pillared by one kind of polyanion through covalent connections
      to generate a sandwich double-sheet. The other kind of polyanion acts as a
      counter-ion and lies in two adjacent sandwich double-sheets through non-covalent
      interactions. Polyanions covalently link metal-organic sheets to extend to an
      unusual 3D 5-connected framework with the (4(4).6(6)) topology in 4. In compound
      5, polyanions link metal-organic chains to form a sheet through covalent
      connections. It is interesting that compound 5 shows an intricate (4,5,10)
      connected framework with (4(4).6(2))(4)(4(8).6(2))(2)(4(14).6(19).8(12)) topology
      based on two kinds of Ag cations as four-connected and five-connected nodes, and
      polyanions as ten-connected nodes, when AgO interactions are considered. It
      represents the highest connected network topology presently known for
      polyoxometalate systems. The structural differences among 1-5 indicate the
      importance of different metal-organic units, coordination modes of polyanions for
      framework formation, and the interactions between polyanions and metal-organic
      units. In addition, the luminescent properties of compounds 1, 2 and 5, and
      electrochemical behaviours of compounds 1-5 have been investigated.

PMID- 18629405
TI  - Multisignaling detection of Hg2+ based on a phosphorescent iridium(III) complex.
AB  - A multisignaling chemosensor for Hg(2+) based on the iridium(III) complex
      Ir(thq)(2)(acac) was realized through UV-Vis absorption, phosphorescent emission
      and electrochemical measurements. Upon addition of Hg(2+), an obvious blue-shift
      in absorption spectra and a strong decrease of emission intensity were measured
      for Ir(thq)(2)(acac), which could be observed by the naked eye. Hg(2+) is
      coordinated to Ir(thq)(2)(acac), forming a 1 : 1 complex. Because Hg(2+) is a
      thiophilic metal ion, the interaction between Hg(2+) and the sulfur atom of
      cyclometalated ligands is responsible for the significant variations in optical
      and electrochemical signals.

PMID- 18629406
TI  - A hexaaza macrocyclic ligand containing acetohydrazide pendants for Ln(III)
      complexation in aqueous solution. Solid-state and solution structures and DFT
      calculations.
AB  - Lanthanide complexes of a hexaaza macrocyclic ligand containing acetohydrazide
      pendants (L) have been synthesised (Ln = La-Er, except Pm), and structural
      studies have been carried out both in the solid state and in aqueous solution.
      Attempts to isolate the complexes of the heaviest Ln(iii) ions (Ln = Tm-Lu) were
      unsuccessful. The crystal structures of the ligand and its lanthanum complex have
      been determined by single-crystal X-ray crystallography. The X-ray crystal
      structure of [La(L)](3+) shows the metal ion being ten-coordinate, with the
      acetohydrazide pendants situated alternatively above and below the plane of the
      macrocycle. The two five membered chelate rings formed by the ethylenediamine
      moieties adopt (deltadelta) [or (lambdalambda)] conformations. The [Ln(L)](3+)
      complexes have been characterised by means of density-functional theory (DFT)
      calculations (B3LYP model). The structures obtained from these theoretical
      calculations are in very good agreement with the experimental solution
      structures, as obtained from paramagnetic NMR measurements on the Ce(iii),
      Pr(III), Nd(III) and Eu(III) complexes. The complexes adopt in aqueous solution a
      D(2) structure with the ligand adopting a (deltadelta) [or (lambdalambda)]
      conformation.

PMID- 18629407
TI  - Kinetics and mechanism of O-O bond cleavage in the reaction of [RuIII(edta)(H2O)]
      with hydroperoxides in aqueous solution.
AB  - The reactions of [Ru(III)(edta)(H(2)O)](-) (1) (edta =
      ethylenediaminetetraacetate) with tert-butylhydroperoxide ((t)BuOOH) and
      potassium hydrogenpersulfate (KHSO(5)) were studied kinetically as a function of
      oxidant concentration and temperature (10-30 degrees C) at a fixed pH of 6.1
      using stopped-flow techniques. Kinetic results were analyzed by using global
      kinetic analysis techniques. The reaction was found to consist of two steps
      involving the rapid formation of a [Ru(III)(edta)(OOR)](2-) intermediate, which
      subsequently undergoes heterolytic cleavage to form [(edta)Ru(V)=O](-). Since
      [(edta)Ru(V)=O](-) was produced almost quantitatively in the reaction of 1 with
      the hydroperoxides (t)BuOOH and KHSO(5), the common mechanism is one of
      heterolytic scission of the O-O bond. The water soluble and easy to oxidize
      substrate 2,2'-azobis(3-ethylbenzithiazoline-6-sulfonate (ABTS), was employed to
      substantiate the mechanistic proposal. Reactions were carried out under pseudo
      first order conditions for [ABTS] >> [hydroperoxide] >> [1], and were monitored
      as a function of time for the formation of the one-electron oxidation product
      ABTS (*+). The detailed suggested mechanism is consistent with the reported rate
      and activation parameters, and discussed in reference to the results reported for
      the reaction of [Ru(II)(edta)(H(2)O)](-) with H(2)O(2).

PMID- 18629408
TI  - Versatile biomimetic dendrimer templates used in the formation of TiO2 and GeO2.
AB  - Biomimetic synthesis is emerging as an advantageous alternative to the harsh
      synthetic conditions traditionally used in metal oxide syntheses techniques.
      Silaffins, proteins from the C. fusiformis diatom, form silica in an aqueous
      environment under benign conditions. Amine terminated PAMAM and PPI dendrimers
      are effective mimics of silaffins and other silica precipitating polyamines. We
      have expanded the scope of dendrimer mediated metal oxide formation to include
      titanium dioxide, a photocatalyst, and germanium dioxide, a blue photoluminescent
      material. The nanoparticles were characterized using scanning electron microscopy
      (SEM), Fourier transform infrared spectroscopy (IR), and X-ray diffraction
      patterns (XRD). A variable temperature XRD analysis of TiO(2) nanoparticles was
      conducted to study the transition from anatase to rutile. TiO(2) nanoparticles
      synthesized in phosphate buffer showed a 200 degrees C decrease in the anatase to
      rutile transition temperature relative to TiO(2) templated in water. XRD analysis
      of GeO(2) nanoparticles in either water or phosphate buffer reveal crystalline
      alpha-phase germanium oxide. To our knowledge, this is the first report of the
      synthesis of crystalline GeO(2) under ambient conditions.

PMID- 18629409
TI  - Interaction of rac-[Cu(diimine)3]2+ and rac-[Zn(diimine)3]2+ complexes with CT
      DNA: effect of fluxional Cu(II) geometry on DNA binding, ligand-promoted exciton
      coupling and prominent DNA cleavage.
AB  - The complexes [Cu(phen)(3)](ClO(4))(2) 1, [Cu(5,6-dmp)(3)](ClO(4))(2) 2,
      [Cu(dpq)(3)](ClO(4))(2) 3, [Zn(phen)(3)](ClO(4))(2) 4, [Zn(5,6
      dmp)(3)](ClO(4))(2) 5 and [Zn(dpq)(3)](ClO(4))(2) 6, where phen = 1,10
      phenanthroline, 5,6-dmp = 5,6-dimethyl-1,10-phenanthroline and dpq = dipyrido[3,2
      d:2',3'-f]quinoxaline, have been isolated, characterized and their interaction
      with calf thymus DNA studied by using a host of physical methods. The X-ray
      crystal structures of rac-[Cu(5,6-dmp)(3)](ClO(4))(2) and rac-[Zn(5,6
      dmp)(3)](ClO(4))(2) have been determined. While 2 possesses a regular elongated
      octahedral coordination geometry (REO), 5 possesses a distorted octahedral
      geometry. Absorption spectral titrations of the Cu(II) complexes with CT DNA
      reveal that the red-shift (12 nm) and DNA binding affinity of 3 (K(b), 7.5 x
      10(4) M(-1)) are higher than those of 1 (red-shift, 6 nm; K(b), 9.6 x 10(3) M(
      1)) indicating that the partial insertion of the extended phen ring of dpq ligand
      in between the DNA base pairs is deeper than that of phen ring. Also, 2 with a
      fluxional Cu(II) geometry interacts with DNA (K(b), 3.8 x 10(4) M(-1)) more
      strongly than 1 suggesting that the hydrophobic forces of interaction of 5,6
      methyl groups on the phen ring is more pronounced than the partial intercalation
      of phen ring in the latter with a static geometry. The DNA binding affinity of 1
      is lower than that of its Zn(ii) analogue 4, and, interestingly, the DNA binding
      affinity 2 of with a fluxional geometry is higher than that of its Zn(II)
      analogue 5 with a spherical geometry. It is remarkable that upon binding to DNA 3
      shows an increase in viscosity higher than that the intercalator EthBr does,
      which is consistent with the above DNA binding affinities. The CD spectra show
      only one induced CD band on the characteristic positive band of CT DNA upon
      interaction with the phen (1,4) and dpq (3,6) complexes. In contrast, the 5,6-dmp
      complexes 2 and 5 bound to CT DNA show exciton-coupled biphasic CD signals with 2
      showing CD signals more intense than 5. The Delta-enantiomer of rac-[Cu(5,6
      dmp)(3)](2+) 2 binds specifically to the right-handed B-form of CT DNA at lower
      ionic strength (0.05 M NaCl) while the Lambda-enantiomer binds specifically to
      the left-handed Z-form of CT DNA generated by treating the B-form with 5 M NaCl.
      The complex 2 is stabilized in the higher oxidation state of Cu(II) more than its
      phen analogue 1 upon binding to DNA suggesting the involvement of electrostatic
      forces in DNA interaction of the former. In contrast, 3 bound to DNA is
      stabilized as Cu(I) rather than the Cu(II) oxidation state due to partial
      intercalative interaction of the dpq ligand. The efficiencies of the complexes to
      oxidatively cleave pUC19 DNA vary in the order, 3> 1 >> 2 with 3 effecting 100%
      cleavage even at 10 microM complex concentration. However, interestingly, this
      order is reversed when the DNA cleavage is performed using H(2)O(2) as an
      activator and the highest cleavage efficiency of 2 is ascribed to its
      electrostatic interaction with the exterior phosphates of DNA.

PMID- 18629410
TI  - Theoretical studies on the reaction mechanism of palladium(0)-catalyzed addition
      of thiocyanates to alkynes.
AB  - The reaction mechanism of the Pd(0)-catalyzed alkyne cyanothiolation reaction is
      investigated by MP2, CCSD(T) and the density functional method B3LYP. The overall
      reaction mechanism is examined. The B3LYP results are consistent with the results
      of CCSD(T) and MP2 methods for the isomerization, acetylene insertion and
      reductive elimination steps, but not for the oxidative addition step. For the
      oxidative addition, the bisphosphine and monophosphine pathways are competitive
      in B3LYP, while the bisphosphine one is preferred for CCSD(T) and MP2 methods.
      The electronic mechanisms for the oxidative addition of thiocyanate HS-CN to
      Pd(PH(3))(2) and Pd(PH(3)) and for the acetylene insertion into Pd-S and Pd-CN
      are discussed in terms of the electron-donation and back-donation. The chemo
      selectivity that acetylene inserts into the Pd-S bond rather than into the Pd-CN
      bond is due to the involvement of the S p orbital. It is the doubly occupied S p
      unhybridized orbital that donates an electron to the alkylene pi* anti-bonding
      orbital, which makes insertion into Pd-S bond more favorable than into the Pd-CN
      bond. During the insertion into the Pd-S bond, the S sp(2) hybrid orbital and
      unhybridized p orbital transform into each other, while the C sp hybrid orbital
      shifts its direction for insertion into Pd-CN bond. By using the monosubstituted
      acetylenes (CN, Me and NH(2)), the influence of substituents at acetylene on the
      chemo- and regio-selectivities is analyzed.

PMID- 18629411
TI  - Synthesis and photophysical properties of multinuclear zinc-salophen complexes:
      enhancement of fluorescence by fluorene termini.
AB  - Incorporation of fluorene groups into the salicylidene moiety significantly
      enhances the luminescence of a number of multinuclear alkynylated Zn(II)-salophen
      complexes. Preparation of these complexes was achieved by a synthetic strategy
      with facile handling of the reactants, simple purification of the products, and
      one-pot reaction process. Two synthetic methods are used for the preparation of
      different types of multinuclear salophen complexes. The introduction of a bis- or
      a tris-salicylaldehyde as a bridging unit in the presence of various alkynyl
      substituted monoimines in the reaction mixture containing zinc acetate resulted
      in the preparation of di- and tri-nuclear Zn(II)-salophen complexes of type 1,
      respectively. For a different type, treatment of tetraminobenzene with various
      arylethynyl-substituted salicylaldehyde afforded dinuclear Zn(II) alkynylated
      salophen complexes of type 2 with a different structure. The photophysical
      behaviors of these multinuclear metal salophen complexes were investigated.
      Particularly, the dinuclear complex 9b of type 1 having ethynylfluorene groups in
      salophen moieties and dialkoxyl groups in the bridging moiety exhibits higher
      quantum efficiency than that of other complexes in this report. In addition, the
      bis-Zn(II) alkynylated salophen complex 11e bearing nitrogen donor groups
      displays more red-shifted pattern than those with other functional substituents
      both in absorption and emission spectra.

PMID- 18629412
TI  - Cycloauration of pyridyl sulfonamides.
AB  - The pyridyl-2-alkylsulfonamides C(5)H(4)N(CH(2))(n)NHSO(2)R (n = 1,2; R = Me, Ph
      or p-C(6)H(4)Me) and 8-(p-tosylamino)quinoline undergo facile cycloauration
      reactions with H[AuCl(4)] in water, giving metallacyclic complexes coordinated
      through the pyridyl (or quinolyl) nitrogen atom and the deprotonated nitrogen of
      the sulfonamide group. The complexes have been fully characterised by NMR
      spectroscopy, ESI mass spectrometry and elemental analysis. The X-ray crystal
      structures of two derivatives reveal the presence of non-planar sulfonamide
      nitrogen atoms. The complexes show low activity against P388 murine leukaemia
      cells, possibly as a result of their ease of reduction with mild reducing agents.

PMID- 18629413
TI  - Temporal cytokine profiling of Francisella tularensis-infected human peripheral
      blood mononuclear cells.
AB  - BACKGROUND AND PURPOSE: Francisella tularensis is an intracellular bacterium
      known to replicate in monocytes and macrophages and cause tularemia in humans.
      Because of its infectious nature, F. tularensis is considered a biowarfare agent.
      Early cytokine profiles of Francisella-infected human peripheral blood
      mononuclear cells were evaluated. METHODS: Populations of human peripheral blood
      mononuclear cells were infected in vitro with F. tularensis live vaccine strain
      at a very low multiplicity of infection of 1:10 (bacteria:cells). A multiplex
      bead kit which analyzes 30 cytokines, chemokines and growth factors was utilized
      to measure secreted cytokines in cell supernatants 1, 4, 8, 16, and 24 h post
      infection. RESULTS: Compared with uninfected controls, infected cells showed no
      increase in cytokine secretion at 1 and 4 h, implying a threshold for activation
      of immune responses. Starting at 8 h post-infection and continuing through to 24
      h, an array of cytokines and growth factors was secreted by the infected cells.
      Some cytokines not previously associated with Francisella infection in humans
      were detected at 8 h, including interleukin-17 and interleukin-1 receptor agonist
      and vascular endothelial growth factor. CONCLUSIONS: The cytokine profiles of F.
      tularensis-infected peripheral blood mononuclear cells indicate an intricate
      pattern of both pro- and anti-inflammatory responses, including early T-cell
      activation.

PMID- 18629414
TI  - Seroprevalence of viral hepatitis and infectious complications among human
      immunodeficiency virus-infected injection drug users at a referral hospital.
AB  - BACKGROUND AND PURPOSE: The seroprevalence of viral hepatitis and spectrum of
      infectious complications among human immunodeficiency virus (HIV)-infected
      injection drug users (IDUs) remains unclear in Taiwan, although there has been a
      significant increase in the prevalence of HIV infection among IDUs in the last 2
      to 3 years. METHODS: The medical records of HIV-infected IDUs who sought medical
      care at a referral hospital for HIV care from June 1994 to December 2006 were
      retrospectively reviewed. A standardized case record form was used to collect
      demographic, clinical, laboratory and microbiologic data. RESULTS: During the 12
      year study period, a total of 102 HIV-infected IDUs with a median age of 39.5
      years (range, 19 to 73 years) sought HIV care at the referral hospital. The male
      to-female case ratio was 6 and males were significantly older than females (39.5
      vs 28 years, p<0.001). The overall median CD4+ cell count and plasma HIV RNA load
      by reverse transcriptase-polymerase chain reaction at enrollment were 374
      cells/microL and 4.45 log(10) copies/mL, respectively. The CD4+ cell count of HIV
      infected IDUs enrolled after year 2003 was significantly higher than those
      enrolled before 2003 (438 vs 23 cells/microL, p<0.001). The seroprevalence of
      hepatitis C virus (86.6% overall) increased over time, while that of hepatitis B
      virus decreased in the patients born after 1984, when nationwide hepatitis B
      vaccination was started in Taiwan. Gram-positive bacteria were causative for
      69.7% of the 33 bacteremic episodes, and Staphylococcus aureus was the leading
      pathogen (16 episodes), with methicillin-sensitive S. aureus accounting for 11
      bacteremic episodes (33.3%). The most common bacterial infection was infective
      endocarditis. Tuberculosis occurred more frequently in men, and extrapulmonary
      tuberculosis was more common than pulmonary tuberculosis and was associated with
      a lower CD4+ count. CONCLUSIONS: Bacteremia, infective endocarditis and
      tuberculosis were the three most common patterns of infection among HIV-infected
      IDUs who sought medical care at a referral hospital; and methicillin-sensitive S.
      aureus was the most common etiology of bacteremia. The high seroprevalence of
      hepatitis B and C and subsequent hepatic complications may present a future
      challenge to the health care system.

PMID- 18629415
TI  - Invasive Haemophilus influenzae disease in adults in Taiwan.
AB  - BACKGROUND AND PURPOSE: Haemophilus influenzae is an important cause of invasive
      infection in infants and children, but it has been considered an uncommon cause
      of invasive disease in adults. We conducted a retrospective survey of invasive H.
      influenzae disease in adults in order to better understand the characteristics of
      clinical presentation and microbiology. METHODS: Patients older than 18 years
      with H. influenzae isolated from normally sterile sites, between July 1999 and
      June 2002 in a teaching hospital for adult patients were retrospectively
      analyzed. Data on demographics, clinical presentation, serotype, antibiotic
      susceptibility, and beta-lactamase production of H. influenzae isolates were
      analyzed. RESULTS: Fifteen patients were enrolled. The infectious diagnosis of
      invasive diseases comprised: pneumonia (5 patients), empyema (2), pelvic
      inflammatory disease (2), peritonitis (2), periorbital cellulitis with abscess
      formation (2), endophthalmitis (1) and primary bacteremia (1). Most patients were
      elderly with underlying illness. Of ten H. influenzae isolates available for
      analysis, two were serotype b and eight were nontypeable. Beta-lactamase
      production and ampicillin resistance were found in 6 H. influenzae isolates (5
      nontypeable, and 1 type b). CONCLUSION: These data show H. influenzae disease in
      adults to be rare in Taiwan. Our limited number of cases suggest that nontypeable
      strains predominate in patients with invasive infection due to H. influenzae.
      Most patients had respiratory tract infections. Ampicillin resistance was found
      in more than one-half of H. influenzae isolates, and should be taken into
      consideration when antibiotics are prescribed on an empirical basis.

PMID- 18629416
TI  - Spinal epidural abscess due to Staphylococcus aureus: clinical manifestations and
      outcomes.
AB  - BACKGROUND AND PURPOSE: Despite advances in diagnosis and treatment, spinal
      epidural abscess due to Staphylococcus aureus remains a challenge to clinicians.
      In this study, we describe the clinical features and outcomes of patients with
      spinal epidural abscess due to S. aureus. METHODS: Thirty one cases of spinal
      epidural abscess due to S. aureus treated at the National Taiwan University
      Hospital from January 2001 to December 2006 were retrospectively reviewed, using
      a standardized case collection form. Spinal epidural abscess was diagnosed by
      computed tomography or magnetic resonance imaging of the spine. RESULTS: The
      median age of subjects was 55 years (range, 20 to 90 years) and the male-to
      female ratio was 4.2. All patients had spine pain and 18 (58.1%) had fever.
      Lumbar or lumbosacral region was the most frequently involved site of spinal
      epidural abscess (61.3%), and 83.9% of the patients also had vertebral
      osteomyelitis. Sixteen patients (51.6%) were treated successfully with
      antibiotics alone for a median duration of 70 days (range, 23 to 274 days),
      whereas the median duration of antibiotic therapy in patients undergoing surgical
      intervention was 102 days (range, 40 to 227 days). Renal failure, malignancy or
      underlying comorbid illness estimated by Charlson score was predictive of a poor
      prognosis with treatment failure or mortality. CONCLUSION: Although medical
      treatment alone might benefit selected patients with spinal epidural abscess due
      to S. aureus and minimal neurologic sequelae, close monitoring of the evolution
      of neurologic deficits with radiographic imaging follow-up is necessary, since
      the rate of progression of neurologic impairment is difficult to predict.

PMID- 18629417
TI  - Clinical significance of Blastocystis hominis: experience from a medical center
      in northern Taiwan.
AB  - BACKGROUND AND PURPOSE: Blastocystis hominis is an intestinal protozoan. The
      pathogenic role of this organism in human beings is still controversial and has
      varied among reports from different geographic areas. The purpose of this study
      was to determine the clinical significance of B. hominis in northern Taiwan.
      METHODS: A total of 100 patients who had a positive B. hominis stool examination
      during the period April to December of 2001 were retrospectively identified from
      Taipei Veterans General Hospital. The demographic and clinical characteristics of
      these patients were reviewed from the medical records. RESULTS: All of the
      patients were adults. Fifty nine patients had more than one underlying diseases,
      including malignancies. Twenty one patients presented with fever and 10 patients
      had gastrointestinal symptoms, including diarrhea and/or abdominal pain. However,
      all of the patients had other conditions that might have contributed to the
      clinical presentation, and they improved without specific treatment for B.
      hominis. Furthermore, there were no significant differences in clinical symptoms
      and white blood cell count between patients with malignancy or diabetes mellitus
      and those without. Six patients had hypereosinophilia that could not be
      attributed to other causes. Among 34 patients who had a further stool examination
      within one year, B. hominis was undetectable in 31 patients (91.2%), despite
      their having no specific antiprotozoal treatment. CONCLUSIONS: The association of
      clinical symptoms and B. hominis could not be delineated from our study, even in
      immunocompromised patients. All of the patients improved without receiving any
      specific therapy. More studies from different areas are needed in order to
      delineate the clinical significance B. hominis.

PMID- 18629418
TI  - Prevalence of hepatitis D virus infection in hepatitis B surface antigen-positive
      subjects in Golestan province, northeast Iran.
AB  - BACKGROUND AND PURPOSE: Hepatitis D virus (HDV) is a defective RNA virus
      dependent on hepatitis B virus (HBV) infection for its replication and
      expression. It is known that coexistent infection with HDV tends to aggravate the
      course of HBV-associated liver disease. This study was carried out to determine
      the seroprevalence of HDV among hepatitis B surface antigen (HBsAg)-positive
      individuals in the northeast part of Iran. METHODS: 139 HBsAg-positive subjects
      detected from a population-based single stage cluster sampling in Golestan
      province of Iran were enrolled. All cases were evaluated for the presence of anti
      HDV antibodies using commercially available enzyme-linked immunoabsorbent assay
      kits. Logistic regression was used to determine the relationship between
      independent variables and HDV seropositivity. RESULTS: Of 139 cases, 68 were
      males (48.9%) and 71 were females (51.1%). The mean age was 41.9 +/- 11.3 years
      (range, 25-64 years). Anti-HDV antibody was positive in 8 subjects (5.8%), with a
      female predominance (9.9% vs 1.5%, p=0.06; odds ratio, 7.32; 95% confidence
      interval, 0.87-61.23). No significant relationship was seen between anti-HDV
      seropositivity and demographic factors such as age, place of residence and
      marital status. CONCLUSIONS: These findings show that HDV infection is endemic in
      Golestan province (northeast) of Iran. Seroprevalence of anti-HDV in the present
      study was higher than in some previous studies from other parts of Iran. Our
      results suggest that the prevalence of HBV/HDV coinfection in Golestan province
      of Iran has increased during the last decade. Therefore, practitioners and health
      care managers should be made aware of the risk of dual infection with HBV and
      HDV.

PMID- 18629419
TI  - Surveillance of avian and swine influenza in the swine population in Taiwan,
      2004.
AB  - BACKGROUND AND PURPOSE: We conducted serological and virological surveillance of
      pig farms in Taiwan from areas epidemic for low pathogenic avian influenza virus
      (AIV), H5N2 subtype, in order to determine the prevalence of AIV and swine
      influenza virus (SIV) in 2004. METHODS: Pig sera from 9833 animals from 1974
      farms in 9 counties were examined using agar gel precipitation (AGP) to screen
      for the presence of antibody against influenza A virus. AGP-positive sera were
      subjected to hemagglutination-inhibition test against H1, H3, H5 and H7 AIV
      subtypes and H1 and H3 SIV subtypes. Nasal swabs from 881 pigs were also examined
      for the presence of SIV by virus isolation in specific pathogen-free embryonated
      chicken eggs. Virus isolates were identified by reverse transcriptase-polymerase
      chain reaction followed by DNA sequencing of hemagglutinin and neuraminidase
      genes. RESULTS: The AGP test on sera revealed the presence of antibodies against
      influenza A virus in 62.6% of farms and in 37.7% of pig sera. SIV antibodies to
      subtype H1 and H3 were found in 10.8% and 65.8% of sera, respectively. There were
      two peaks of the serological prevalence of SIV in pigs: one between January and
      February, and the other in October. By contrast, hemagglutinin tests against H5
      and H7 AIV subtypes were negative in all sera, while there was a very low
      positive rate against H1 and H3 AIV subtypes. One H1N2 and one H3N1 viral isolate
      were obtained from nasal swabs of pigs. Phylogenetic analysis of hemagglutinin
      and neuraminidase genes revealed both isolates were reassortants of both
      classical and recent SIVs. CONCLUSIONS: Different subtypes of SIV co-circulate
      among swine from different farms within the same county and may cause clinical
      outbreaks of the disease in Taiwan.

PMID- 18629420
TI  - Quantification of Proteus mirabilis virulence factors and modulation by acylated
      homoserine lactones.
AB  - BACKGROUND AND PURPOSE: Measurement of the main Proteus mirabilis virulence
      factors would increase our understanding of how the organism infects and
      colonizes the urinary tract. The purpose of this study was to quantify the
      virulence factors of twelve P. mirabilis laboratory strains and to determine
      whether expression of virulence factors of P. mirabilis depends on the presence
      of homoserine-lactone derivatives. METHODS: Twelve P. mirabilis strains with
      defined lipopolysaccharide structures were used. The activity levels of urease,
      proteases, and hemolysins and the swarming abilities of P. mirabilis rods were
      tested by qualitative and quantitative methods. The effect of addition of
      acylated homoserine lactones (acyl-HSLs) was evaluated in order to determine
      their influence on the pathogenic features of the P. mirabilis strains. RESULTS:
      The ureolytic, proteolytic, and hemolytic abilities and the swarming motility of
      P. mirabilis rods were strain-specific. The P. mirabilis strains which possessed
      a negatively charged O-polysaccharide demonstrated strong ureolytic and
      proteolytic properties and faster migration speed on solid media. There was no
      influence of acyl-HSLs on the process of urea decomposition. The acyl-HSLs
      inhibited the protease activity of five P. mirabilis strains. N-butanoyl-L
      homoserine lactone accelerated the migration speed of the tested P. mirabilis
      strains. CONCLUSIONS: The levels of tested virulence factors were strain
      specific. The acetylated homoserine lactone derivatives modified the expression
      of some virulence factors of the P. mirabilis strains.

PMID- 18629421
TI  - Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children.
AB  - BACKGROUND AND PURPOSE: Major hepatotropic viruses continue to be important
      causes of acute viral hepatitis in developing countries. This work was carried
      out to detect the seroprevalence of hepatitis E virus (HEV) markers in children
      with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A,
      non-B, non-C acute hepatitis, and to ascertain the influence of HEV
      superinfection in individuals infected with hepatitis viruses (A, B and C).
      METHODS: We studied prospectively 162 children with sporadic acute hepatitis who
      reported to our hospital. Thirteen healthy controls were also included in the
      study. Laboratory investigations were performed, including complete liver
      function tests. Complete serological profiles for hepatitis viruses A, B, C and E
      were evaluated. RESULTS: HEV immunoglobulin G was detected with highest
      percentage among patients with hepatitis B (56.7%), followed by patients with
      hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and
      C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C
      hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus
      patients and in 3.3% of hepatitis B patients. The prevalence of HEV
      immunoglobulin G and immunoglobulin M correlated with the levels of hepatic
      aspartate aminotransferase and alanine aminotransferase in patients with dual
      markers of infection with hepatitis E and other viruses compared to patients with
      acute hepatitis due to A and C viruses. CONCLUSIONS: HEV serological markers are
      common among children with acute viral hepatitis, especially from hepatitis C and
      B viruses. There may be increased sensitivity to HEV coinfection in association
      with hepatitis B and C infections. Dual infection with HEV and other hepatotropic
      viruses was associated with greater elevation of aspartate and alanine
      aminotransferases.

PMID- 18629422
TI  - Rapid identification and susceptibility testing using the VITEK 2 system using
      culture fluids from positive BacT/ALERT blood cultures.
AB  - BACKGROUND AND PURPOSE: In order to reduce the turnaround time for laboratory
      diagnosis of bacteremia, the efficacy of identification and antimicrobial
      susceptibility testing using samples taken directly from positive BacT/ALERT
      standard aerobic and standard anaerobic blood culture bottles was evaluated.
      METHODS: 160 positive blood culture bottles were examined and incubated at 35
      degrees C in 5% carbon dioxide for 4-24 h, and an aliquot of the culture fluid
      was Gram stained. Samples containing Gram-negative bacilli were inoculated on
      VITEK 2 ID-GNB (identification-Gram-negative bacilli) and AST (antimicrobial
      susceptibility testing)-GN04 cards, and those containing Gram-positive cocci were
      inoculated on ID-GPC (identification-Gram-positive cocci) and AST-P526 cards. The
      same samples were also examined by the standard method, involving subculture from
      positive BacT/ALERT standard blood culture bottles. RESULTS: Eighty seven of 97
      Gram-negative bacilli (89.7%) and 21 of 63 Gram-positive cocci (33.3%) were
      correctly identified to the species level. For antimicrobial susceptibility
      testing, the direct method had an overall error rate of 5.4% for Gram-negative
      bacilli, with 0.9% very major, 0.9% major, and 3.6% minor discrepancies compared
      to the standard method. The overall error rate in antimicrobial susceptibility
      testing for the 13 Staphylococcus spp. was 10.3%, with 6.0% very major, 2.6%
      major, and 1.7% minor discrepancies. CONCLUSION: These data suggest that VITEK 2
      cards inoculated with samples taken directly from positive Bact/ALERT blood
      culture bottles would provide acceptable identification and antimicrobial
      susceptibility testing results for Gram-negative bacilli, but not for Gram
      positive cocci. Compared to the standard method, the direct method would reduce
      turnaround time by at least 24 h.

PMID- 18629423
TI  - Host defense against Salmonella and rotaviral gastroenteritis: a serial study of
      transcriptional factors and cytokines.
AB  - BACKGROUND AND PURPOSE: Common etiologies of acute enterocolitis in childhood
      include the intracellular pathogens Salmonella and rotavirus, along with
      extracellular pathogens. In order to elucidate differentiating immunologic
      parameters in patients with acute gastroenteritis of different etiologies, we
      investigated interferon (IFN)-gamma, interleukin (IL)-12, and T-bet of T-helper
      type 1 subsets, and IL-4 and GATA-3 of T-helper type 2 subsets. METHODS: From
      June 1, 2003 to December 31, 2003, 32 patients with acute gastroenteritis were
      enrolled. Sequential heparinized blood samples were obtained on the day of
      presentation (day 1) and on day 3 of hospitalization. Using reverse transcriptase
      polymerase chain reaction, the mean ratios of IFN-gamma, T-bet and IL-12 mRNA
      levels relative to beta-actin were determined. RESULTS: Salmonella infections
      induced stronger IFN-gamma and T-bet responses than either rotavirus infection or
      other enterocolitis (p<0.05). However, poor IL-12 response in Salmonella
      infections implied failed T-helper type 1 immunity, and probably accounted for
      the prolonged clinical course. In contrast, by day 3 of hospitalization, most
      patients with rotavirus enterocolitis were symptom-free. CONCLUSIONS: IL-12 is
      the key factor in determining host response against and, hence, disease activity
      of Salmonella infections.

PMID- 18629424
TI  - Peritoneal dialysis-related peritonitis caused by Gemella morbillorum in a
      patient with systemic lupus erythematosus receiving steroid therapy.
AB  - Gemella morbillorum, a Gram-positive coccus, is a natural inhabitant of the human
      oropharyngeal, upper respiratory and gastrointestinal tracts. Human infections
      caused by this organism are rare. We describe a case of peritoneal dialysis
      related peritonitis due to G. morbillorum in a patient with systemic lupus
      erythematosus receiving steroid therapy. The patient responded well to
      antibiotics, without removal of the peritoneal catheter.

PMID- 18629425
TI  - Tuberculosis of the shoulder joint with impingement syndrome as initial
      presentation.
AB  - Tuberculosis of the shoulder can be difficult to diagnose in the early stages. If
      not diagnosed early, bony tuberculosis may reduce quality of life. Therefore,
      tuberculosis should be suspected in cases of long-standing pain in the shoulder.
      It is necessary to keep tuberculosis in the differential diagnosis of impingement
      syndrome of the shoulder. We report a young patient presenting with features
      suggestive of impingement syndrome. After failure to improve with adequate
      therapy, the patient was further investigated and diagnosed as having early
      tuberculosis of the shoulder joint. The patient had good clinical recovery with
      conservative management. The importance of considering early tuberculosis as a
      differential diagnosis in impingement syndrome is highlighted.

PMID- 18629426
TI  - Guidelines for antimicrobial therapy of intra-abdominal infections in adults.

PMID- 18629427
TI  - Voiding dysfunction due to long-standing labial fusion in an elderly woman: a
      case report.
AB  - Labial adhesions or fusion in the elderly are rare, and only few cases are
      described in the English literature. We describe a case of near-complete labial
      fusion in an elderly woman presenting with voiding difficulty, its management and
      literature review.

PMID- 18629429
TI  - The effect of in vitro exposure to tributyltin on the immune competence of
      Chinook salmon (Oncorhynchus tshawytscha) leukocytes.
AB  - We evaluated the direct effects of in vitro exposures to tributyltin (TBT), a
      widely used biocide, on the cell-mediated immune system of Chinook salmon
      (Oncorhynchus tshawytscha). Splenic and pronephric leukocytes isolated from
      juvenile Chinook salmon were exposed to TBT (0, 0.1, 0.2, 0.3, 0.4, 0.5, and 0.6
      mg/l) in cell cultures for 24 h. Effects of TBT on cell viability, induction of
      apoptosis, and mitogenic responses were measured by flow cytometry. Splenic and
      pronephric leukocytes in the presence of TBT experienced a concentration
      dependent decrease in viability in cell cultures. Apoptosis was detected as one
      of the mechanisms of cell death after TBT exposure. In addition, pronephric
      lymphocytes exhibited a greater sensitivity to TBT exposure than pronephric
      granulocytes. The functional ability of splenic B-cells to undergo blastogenesis
      upon lipopolysaccharide stimulation was also significantly inhibited in the
      presence of 0.05, 0.07, or 0.10 mg/l of TBT in the cell cultures. Flow cytometric
      assay using a fluorescent conjugated monoclonal antibody against salmon surface
      immunoglobulin was employed for the conclusive identification of B-cells in the
      Chinook salmon leukocytes. Our findings suggest that adverse effects of TBT on
      the function or development of fish immune systems could lead to an increase in
      disease susceptibility and its subsequent ecological implications.

PMID- 18629428
TI  - Adaptive and slightly deleterious evolution in a conifer, Cryptomeria japonica.
AB  - In order to evaluate effects of the population structure and natural selection on
      organisms having long generation times, we surveyed DNA polymorphisms at five
      loci encoding 9-cis-epoxycarotenoid dioxygenase (NCED), ammonium transporter,
      calmodulin, aquaporin, and the second major allergen with polymethylgalacturonase
      enzyme activity in the pollen (Cryj2) in a conifer, Cryptomeria japonica. The
      average nucleotide diversity at silent sites across 12 loci including the
      previously analyzed seven loci was 0.0044. The population recombination rate
      (4Nr, where N and r are the effective population size and recombination rate per
      base per generation, respectively) was estimated as 0.00046 and a slow reduction
      in the population size was indicated, according to the maximum likelihood method
      implemented in LAMARC. At NCED, the McDonald-Kreitman (MK) test revealed an
      excess of replacement polymorphisms, suggesting contributions of slightly
      deleterious mutations. In contrast, the MK test revealed an excess of replacement
      divergence at Cryj2 and a maximum likelihood approach using the PAML package
      revealed that certain amino acid sites had a nonsynonymous/synonymous
      substitution rate ratio (omega) > 4.0, indicating adaptive evolution at this
      locus. The overall analysis of the 12 loci suggested that adaptive, neutral, and
      slightly deleterious evolution played important roles in the evolution of C.
      japonica.

PMID- 18629430
TI  - Blushing propensity in social anxiety disorder: influence of serotonin
      transporter gene variation.
AB  - Blushing is considered to be one of the prime pathophysiological markers of
      social anxiety disorder, potentially mediated by serotonergic function.
      Therefore, in the present study 62 patients with social anxiety disorder and 62
      age- and sex-matched healthy controls were investigated for the influence of
      serotonin transporter (5-HTT) gene variation (5-HTTLPR, rs25531) on blushing
      propensity as measured by the blushing propensity scale (BPS). The less active 5
      HTTLPR genotypes were nominally significantly associated with increased blushing
      propensity in patients with social anxiety disorder as compared to controls with
      an equidirectional trend for the less active 5-HTTLPR/rs25531 haplotypes. Even
      when statistically controlled for influence of depression, this association
      remained significant. In summary, the present pilot study suggests a potential
      role of functional serotonin transporter gene variation in blushing propensity
      warranting replication and encouraging genetic analyses of further intermediate
      phenotypes of social anxiety disorder.

PMID- 18629431
TI  - Sympathetic activity relates to adenosine A(2A) receptor gene variation in blood
      injury phobia.
AB  - Variation in the candidate genes adenosine A(2A) receptor (A(2A)R), catechol-O
      methyl-transferase (COMT), and norepinephrine transporter (NET) has been
      suggested to influence vulnerability to panic disorder. We therefore investigated
      patients with another anxiety disorder with an even higher heritability, the
      blood-injury phobia, for association of these variants and used sympathetic
      measures during venipuncture, which serve as a naturalistic trigger of anxiety
      and autonomic hyperarousal, as an intermediate phenotype of anxiety. Patients
      homozygous for the A(2A)R 1976T allele as compared to patients carrying at least
      one 1976C allele exhibited a significantly increased respiratory rate with a
      trend towards elevated measures of systolic and diastolic blood pressure and
      respiratory minute volume. None of the sympathetic measures were influenced by
      the COMT or NET polymorphisms.This study provides preliminary data suggesting an
      influence of the A(2A)R 1976C/T polymorphism on sympathetic psychophysiological
      indicators of anxiety-related arousal in blood-injury phobia and thereby further
      supports a role of the A(2A)R gene in the pathogenesis of anxiety disorders.

PMID- 18629432
TI  - Neuropsychological characteristics as predictors of SSRI treatment response in
      depressed subjects.
AB  - Studies suggest that neuropsychological measures may provide prognostic
      information regarding SSRI treatment response, yet it is unclear which specific
      cognitive domains are the most effectual predictors. The aim of this study was to
      characterize the cognitive profile associated with SSRI nonresponse using a
      comprehensive set of neuropsychological tests. Participants (N = 32) met criteria
      for current major depressive episode. Assessment followed pre-treatment
      medication washout. Clinical response was measured after 3-month open-label SSRI
      treatment. Groups did not differ by demographic characteristics, intelligence or
      depression severity. Responders outperformed nonresponders across all cognitive
      domains, with the largest differences observed in executive, language and working
      memory functions. Results indicate poorer global cognitive functioning is
      predictive of treatment nonresponse. Deficits were most pronounced in tests
      demanding greater mental search and manipulation rather than speeded motor
      output. Cognitive slowing may mediate the working memory and executive function
      deficits found in nonresponders. These findings can inform exploration for
      pharmacogenetic endophenotypes.

PMID- 18629433
TI  - Downhill training upregulates mice hippocampal and striatal brain-derived
      neurotrophic factor levels.
AB  - This study examined the effects of downhill treadmill exercise on brain-derived
      neurotrophic factor (BDNF) protein on the hippocampus and striatum of mice.
      Twenty-four adult mice were assigned to three groups: non-runners control, level
      or downhill (16 degrees decline) running exercise. The exercise schedule
      consisted of progressive treadmill running for 5 days week(-1) over 8 weeks.
      Blood lactate levels classified exercise intensity as moderate to high. Both
      training types increased citrate synthase activity of the soleus muscle when
      compared to untrained controls. While level running increased BDNF levels
      selectively in the hippocampus (68.5%), the eccentric running resulted in a
      pronounced BDNF increase in both the hippocampus (137.0%) and the striatum
      (49.9%). Further studies will specify whether the observed alterations in BDNF
      are due to downhill-induced upregulation or complex learning-induced mechanisms
      that influence BDNF levels in these brain regions.

PMID- 18629434
TI  - Acinetobacter sp. strain Ths, a novel psychrotolerant and alkalitolerant
      bacterium that utilizes hydrocarbon.
AB  - A novel psychrotolerant, alkalitolerant bacterium, strain Ths, was isolated from
      a soil sample immersed in hot spring water containing hydrocarbons and grown on a
      chemically defined medium containing n-tetradecane as the sole carbon source. The
      isolate grew at 0 degrees C but not at temperatures higher than 45 degrees C; its
      optimum growth temperature was 27 degrees C. It grew in the pH range of 7-9. The
      strain utilized C(13)-C(30) n-alkane and fluorene at pH 9 and 4 degrees C. To our
      knowledge, this is the first report on the bacterium that utilizes a wide range
      of hydrocarbons at a high pH and a low temperature. Phylogenetic analysis based
      on 16S rRNA gene sequences showed that strain Ths is closely related to genomic
      species 6 ATCC 17979 (99.1% similarity), genomic species BJ13/TU14 ATCC 17905
      (97.8% similarity), genomic species 9 ATCC 9957 (97.6% similarity) belonging to
      the genus Acinetobacter and to Acinetobacter calcoaceticus JCM 6842(T) (97.5%
      similarity). DNA-DNA hybridization revealed that the isolate has 62, 25, 18 and
      19% relatedness, respectively, to genomic species 6 ATCC 17979, genomic species
      BJ13/TU14 ATCC 17905, genomic species 9 ATCC 9957 and A. calcoaceticus,
      respectively.

PMID- 18629436
TI  - The impact of age on the demographic, clinical, radiographic characteristics and
      treatment outcomes of pulmonary tuberculosis patients in Taiwan.
AB  - BACKGROUND: The characteristics of pulmonary tuberculosis (TB) in the elderly are
      different from young patients. This leads to delay in diagnosis and higher
      mortality from TB in the aged population. The aim of this study was to
      investigate the impact of age on the demographic, clinical, radiographic
      characteristics, and treatment outcomes of pulmonary TB patients in Taiwan.
      MATERIALS AND METHODS: We performed a retrospective analysis of the medical
      charts and chest radiographs of 83 elderly (> or =60 years old) and 74 young (<
      60 years old) culture-proven pulmonary TB patients from 1 August 2003 to 31 July
      2006. RESULTS: Elderly patients showed lower frequencies of infectious TB contact
      history, alcoholism, cavity, and positive acid-fast bacilli sputum smears. In
      contrast, the elderly population had higher frequencies of chronic obstructive
      lung disease, heart failure, stroke, dyspnea, lower lung field involvement,
      pleural effusion and mortality. There were no differences between these two
      groups regarding sex, initial body weight, previous TB disease, hospital
      admission, diabetes mellitus, end-stage renal disease, neoplasm, liver cirrhosis,
      upper lung field involvement, cure, and treatment completion. Furthermore, age of
      60 and older, lower initial body weight less than 50 kg, coexisting medical
      diseases, and extensive radiographic disease were factors independently
      associated with unfavorable outcomes. CONCLUSIONS: Elderly patients with
      pulmonary TB are more likely to present with negative sputum smears, cavity
      negative lesions, lower lung field involvement and pleural effusion on chest
      radiographs. The prognosis is poor for the elderly pulmonary TB patients with
      lower body weight, coexisting medical diseases, and extensive radiographic
      disease.

PMID- 18629435
TI  - Successful long-term treatment with linezolid for disseminated infection with
      multiresistant Nocardia farcinica.

PMID- 18629437
TI  - The response to pegylated interferon alpha 2a in haemodialysis patients with
      hepatitis C virus infection.
AB  - The aim of this retrospective study was to focus the efficacy of pegylated
      interferon (PEG-IFN) alpha 2a in chronic hemodialysis patients with hepatitis C
      and to compare the therapy responses with other chronic hepatitis C patients. Of
      the anti-HCV positive patients who were admitted to the Infectious Diseases and
      Clinical Microbiology policlinic from January 2004 to December 2006, 99 were
      candidates for interferon therapy. Of those, 12 patients were on HD. We began 47
      patients on PEG-IFN alpha 2a (180 lg/week) subcutaneously plus ribavirin (1,000
      1,200 mg/day) (Group 1), and 12 patients on HD, PEG-IFN alpha 2a, without
      ribavirin at a dose of 135 lg weekly for 48 weeks (Group 2). In this study of PEG
      IFN alpha 2a with or without ribavirin, the predictability of a sustained viral
      response (SVR) was based on the early virologic response (EVR) defined at week 12
      as an at least 2-log decline from baseline of the HCV RNA level. About 77%
      (39/47) of patients achieved an EVR in Group 1 and 58% (7/12) in Group 2 (p =
      0.004). A total of 34 (72.34%) patients in Group 1 and 6 patients (50%) in Group
      2 had negative HCV RNA at the end of the treatment (p = 0.213). We evaluated SVR
      after 6 months finishing the therapy; 29 (61.7%) patients in Group 1 and 6
      patients (50%) in Group 2 had negative HCV RNA (p = 0.109). PEG-IFN alpha 2a (135
      lg weekly) for 48 weeks is efficacious and well tolerated in HD patients with
      HCV, as well as other chronic HCV patients. However, due to more side effects of
      IFN specially on platelet counts as compared non-renal HCV patients a closer
      follow-up, in HD patients is suggested.

PMID- 18629438
TI  - Simultaneous degradation of phytic acid and starch by an industrial strain of
      Saccharomyces cerevisiae producing phytase and alpha-amylase.
AB  - Phytase liberates inorganic phosphate from phytic acid (myo-inositol
      hexakisphosphate) which is the major phosphate reserve in plant-derived foods and
      feeds. An industrial strain of Saccharomyces cerevisiae expressing the
      Debaryomyces castellii phytase gene (phytDc) and D. occidentalis alpha-amylase
      gene (AMY) was developed. The phytDc and AMY genes were constitutively expressed
      under the ADC1 promoter in S. cerevisiae by using the delta-integration system,
      which contains DNA derived exclusively from yeast. The recombinant industrial
      strain secreted both phytase and alpha-amylase for the efficient degradation of
      phytic acid and starch as main components of plant seeds. This new strain
      hydrolyzed 90% of 0.5% (w/v) sodium phytate within 5 days of growth and utilized
      100% of 2% (w/v) starch within 48 h simultaneously.

PMID- 18629439
TI  - Evaluation of Epicoccum nigrum for growth, morphology and production of natural
      colorants in liquid media and on a solid rice medium.
AB  - Four nonpathogenic and nontoxigenic Epicoccum nigrum strains were evaluated for
      their growth, morphology and pigment producing ability in three complex and one
      defined liquid media. Epicoccum nigrum IBT 41028 produced pigments in all the
      four media tested with a maximum pigment of 3.68 AU at 410 nm in M1 medium
      (unoptimized) containing 5 g/l yeast autolysate. The color hue of the crude
      pigment extracts ranged from 74 to 102 exhibiting dark orange to green-yellow
      color. Pelleted morphology was shown to have a positive influence on the pigment
      production by E. nigrum strain IBT 41028 in the liquid media, and the use of Bis
      tris buffer was found to diminish or reduce the pellet formation. Since Monascus
      is a well known pigment producer on rice. Pigment producing ability of E. nigrum
      IBT 41028 was tested on rice and compared to liquid media with Monascus ruber IBT
      7904 as control. Though, both genera preferred rice but E. nigrum produced 4.6
      folds higher pigment in the liquid unoptimized fermentation medium compared to M.
      ruber. Solid phase extraction and subsequently HPLC-DAD analysis of the crude
      pigment extracts showed qualitative as well as quantitative variation in the
      pigment composition under solid and liquid cultivations.

PMID- 18629440
TI  - Over-expression of recombinant human phospholipid scramblase 1 in E. coli and its
      purification from inclusion bodies.
AB  - Human phospholipid scramblase 1 (hPLSCR1) scrambles plasma membrane phospholipids
      during cell activation, blood coagulation and apoptosis. It was over-expressed in
      E. coli with a histidine tag and purified from the inclusion bodies (*30 mg/l
      culture broth) under denaturing conditions using 8 M urea. The denatured hPLSCR1
      refolded into its native configuration when urea was removed as shown by a 10
      fold increase in its intrinsic fluorescence. Active hPLSCR1 showed scrambling
      activity in vitro after reconstituting in proteoliposomes. hPLSCR1 showed higher
      rates of scrambling activity for phosphatidylethanolamine than
      phosphatidylcholine. Binding studies with the calcium analogue "Stains-all" dye
      showed a characteristic peak, termed as the J band, at 650 nm. This is the first
      report on high level expression of hPLSCR1 with histidine tag in E. coli.

PMID- 18629441
TI  - Effects of soil amendments on the bioavailability of heavy metals from zinc mine
      tailings.
AB  - A study was conducted to test the effects of soil amendments on the
      bioavailability of heavy metals in a zinc mine tailings containing soil to
      plants, using the Indian mustard plant (Brassica juncea) as a test organism. Zinc
      mine tailing containing soil was amended with humus soil (HS) and phosphatic clay
      (PC). The zinc mine tailing containing soil (ZMTS) was characterized for heavy
      metals. It was mixed with PC and HS, and four mixtures were prepared. The first
      mixture contained ZMTS, and served as a control. The second mixture contained
      ZMTS and PC in the ratio of 1:1 (w/w). The third mixture contained ZMTS and HS in
      the ratio of 1:1(w/w). The fourth mixture containing ZMTS, PC and HS in the ratio
      of (2:1:1) (w/w). A slight increase in the bioavailability of Pb, Cu, Zn and Mn
      was noticed with increase in the incubation time from 14 to 42 days. The
      bioavailability of Pb, Cu, Zn and Mn from ZMTS alone in Brassica plant was in the
      range of 94-99% up to 42 days. Addition of PC and HS to the ZMTS soil reduced the
      bioavailabilities of Pb by (15%), of Cu by (20%), of Zn by (20%) and of Mn by
      (25%) in the mustard plant. The data showed that PC in the presence of HS had a
      high affinity for the heavy metals in the order of Pb, Cu, Zn and Mn.

PMID- 18629442
TI  - The effects of construction on water quality: a case study of the culverting of
      Abram Creek.
AB  - While sediment is a leading cause of impaired water, studies have shown that
      construction activities incorporating best management practices (BMPs) can be
      conducted without lasting detrimental effects on water quality. This paper
      examines the water quality impacts of a construction project involving the
      culverting of a creek to allow for the construction of a runway at an airport in
      Cleveland, Ohio. Sampling parameters included total suspended solids (TSS),
      dissolved oxygen (DO), pH, conductivity, and temperature. To assess the effects
      of the construction project conducted using appropriate BMPs, weekly water
      quality samples were taken upstream and downstream from the construction site.
      The samples were categorized as baseline, active construction, and post
      construction to isolate the effects of the construction activities. t tests were
      used to compare upstream and downstream data for each of the parameters and ANOVA
      was used to compare the individual water quality parameters in the three sampling
      periods to see if there were significant increases or decreases of the water
      quality parameters within the phases. Results of ANOVA indicate there were no
      statistically significant differences between upstream and downstream in the mean
      sample results for TSS, conductivity, and pH when comparing the three phases.
      While the descriptive statistics conducted on the data illustrated minor
      variation in the upstream, downstream, and between phase comparisons, the results
      of the t tests helped to strengthen the theory that construction projects
      utilizing appropriate BMPs can yield minimal impact on overall water quality of
      surrounding water bodies.

PMID- 18629443
TI  - Studies on antioxidant status in Mugil cephalus in response to heavy metal
      pollution at Ennore estuary.
AB  - Estuaries, the important component of natural environment are under pressure
      nowadays due to pollution from different sources like industries, agricultural
      fields etc. Ennore estuary one of the highly polluted estuary situated in
      Chennai, Tamilnadu, India, due to heavy industrialization surrounding this site
      poses serious threat to its inhabitants. The present paper focuses on studying
      the response of the fish Mugil cephalus with reference to its antioxidants during
      their exposure to metals like iron and chromium present in the industrial
      effluents that are discharged into the Ennore estuary. The results on comparison
      with unpolluted Kovalam estuary showed that fish from Ennore experiences severe
      oxidative stress with significant alteration being observed with antioxidant
      enzyme activities. Since these results were also found to vary with seasons, the
      determination of oxidative stress biomarkers in M. cephalus along with seasonal
      variations may serve as a convenient approach during pollution biomonitoring
      programme.

PMID- 18629444
TI  - The relative influence of geographic location and reach-scale habitat on benthic
      invertebrate assemblages in six ecoregions.
AB  - The objective of this study was to determine the relative influence of reach
      specific habitat variables and geographic location on benthic invertebrate
      assemblages within six ecoregions across the Western USA. This study included 417
      sites from six ecoregions. A total of 301 taxa were collected with the highest
      richness associated with ecoregions dominated by streams with coarse substrate
      (19-29 taxa per site). Lowest richness (seven to eight taxa per site) was
      associated with ecoregions dominated by fine-grain substrate. Principle component
      analysis (PCA) on reach-scale habitat separated the six ecoregions into those in
      high-gradient mountainous areas (Coast Range, Cascades, and Southern Rockies) and
      those in lower-gradient ecoregions (Central Great Plains and Central California
      Valley). Nonmetric multidimensional scaling (NMS) models performed best in
      ecoregions dominated by coarse-grain substrate and high taxa richness, along with
      coarse-grain substrates sites combined from multiple ecoregions regardless of
      location. In contrast, ecoregions or site combinations dominated by fine-grain
      substrate had poor model performance (high stress). Four NMS models showed that
      geographic location (i.e. latitude and longitude) was important for: (1) all
      ecoregions combined, (2) all sites dominated by coarse-grain sub strate combined,
      (3) Cascades Ecoregion, and (4) Columbia Ecoregion. Local factors (i.e. substrate
      or water temperature) seem to be overriding factors controlling invertebrate
      composition across the West, regardless of geographic location.

PMID- 18629445
TI  - Dependency of phenprocoumon dosage on polymorphisms in the VKORC1 and CYP2C9
      genes.
AB  - OBJECTIVES: Polymorphisms in the vitamin K epoxide-reductase-complex-1 (VKORC1)
      and the cytochrome-P450-isozyme (CYP2C9) genes account for therapeutic responses
      to vitamin K antagonists (VKA). This study aimed to investigate the prevalence of
      VKORC1 and CYP2C9 polymorphisms among patients under phenprocoumon and its
      influence on the VKA dosage. METHODS: Patients under phenprocoumon were screened
      for the polymorphisms -1639G > A and 3730G > A in the VKORC1 gene and 430C > T
      and 1075A > C in the CYP2C9 gene by means of a StripAssay. Baseline clinical and
      laboratory parameters were registered. RESULTS: Among 53 patients (28 females,
      mean age 72.5 years), VKORC1 polymorphisms were found in 34 [-1639G > A:
      homozygote (n = 11), heterozygote (n = 23)] and 28 [3730G > A: homozygote (n =
      7), heterozygote (n = 21)] patients. Thirteen patients were compound
      heterozygote. CYP2C9 polymorphisms were found in 12 [430G > T: homozygote (n =
      1), heterozygote (n = 11)] and 7 [1075A > C: homozygote (n = 0), heterozygote (n
      = 7)] patients. Seventeen patients had at least one VKORC1 and one CYP2C9
      polymorphism. Mean phenprocoumon dosage per week to achieve therapeutic
      anticoagulation was lower (higher) in patients with than without the VKORC1
      polymorphism -1639G > A (3730G > A) or the CYP2C9 polymorphisms. Despite the
      presence of VKORC1 or CYP2C9 polymorphisms, mean International Normalized Ratio
      was not significantly different between patients with and without polymorphisms.
      CONCLUSIONS: Though VKORC1 and CYP2C9 polymorphisms influence the phenprocoumon
      dosage necessary to achieve therapeutic anticoagulation, anticoagulation is
      therapeutic if carefully monitored.

PMID- 18629446
TI  - Acute in-vivo evaluation of bleeding with Gelfoam plus saline and Gelfoam plus
      human thrombin using a liver square lesion model in swine.
AB  - BACKGROUND: Management of post-operative bleeding has historically used topical
      bovine thrombin. However, possible harm through activation of coagulation
      inhibitors has encouraged investigation with other hemostatic agents. This study
      utilized a novel ordinal bleeding model to test whether a Gelfoam + human
      thrombin solution is superior at controlling bleeding when compared to Gelfoam +
      saline solution at different time intervals. STUDY DESIGN: Four swine underwent
      open laparotomy after receiving unfractionated heparin. Twenty open liver
      biopsies were performed in each swine; ten biopsies treated with Gelfoam + human
      thrombin solution and 10 biopsies treated with Gelfoam + saline solution. Three,
      6 min, and 12 min after the procedure, bleeding was objectively graded by a four
      point model. RESULTS: There was a significant (P < 0.017), treatment effect on
      each success/failure outcome (success = bleeding score <or= 1; failure = bleeding
      score > 1) at 3 (P < 0.001), 6 (P < 0.001), and 12 (P = 0.003) min, based on a 2
      x 2 Fisher's exact test. Similarly, there was a significant treatment effect on
      each success/failure outcome and four-point bleeding score based on a multiple
      logistic regression analysis controlling for pig, lesion weight, and initial
      bleeding taking into consideration repeated measures at three time points.
      CONCLUSIONS: The results demonstrate a superior treatment effect for control of
      bleeding using human thrombin compared to a saline solution. Future studies
      should compare bovine thrombin versus human thrombins ability to control bleeding
      as well as the hazard of each in activating coagulation inhibitors.

PMID- 18629447
TI  - Types of bone metastases in women with breast cancer undergoing systemic
      treatments.

PMID- 18629448
TI  - Autoimmunity in the immune privileged eye: pathogenic and regulatory T cells.
AB  - Experimental autoimmune uveitis (EAU) in animals serves as a model of human
      uveitis. EAU can be induced in mice by immunization with the retinal antigen
      interphotoreceptor retinoid binding protein (IRBP) in complete Freund's adjuvant
      (CFA) or by IRBP-pulsed mature dendritic cells, and can be driven either by a
      Th17 or a Th1 effector response, depending on the model. The direction of the
      response is affected by conditions present during the exposure to antigen,
      including the quality/quantity of innate receptor stimulation and/or type of APC.
      IL-17 and IFN-gamma production by innate cells such as NKT may also affect the
      disease process. If exposure to antigen is via a hydrodynamic DNA vaccination
      with an IRBP-encoding plasmid, the response is directed to a regulatory
      phenotype, and disease is ameliorated or prevented. Our data shed light on
      effector and regulatory responses in autoimmune disease, provide balance to the
      Th1/Th17 paradigm and help to explain the clinical heterogeneity of human
      uveitis, which occurs in the face of responses to the same ocular antigen(s).

PMID- 18629450
TI  - [Interventional therapy of supraventricular dysrhythmia].

PMID- 18629452
TI  - [Pharmaceutical treatment of atrial fibrillation].
AB  - Atrial fibrillation is one of the most common long-lasting arrhythmias of the
      heart. It leads to an increase in morbidity and a substantial reduction in
      quality of life in most patients. Therefore, an early and adequate therapy
      strategy and prevention of comorbidities of atrial fibrillation are demanding.
      There is no controversy about the pharmaceutical treatment as the first choice
      and gold standard in atrial fibrillation patients. As there is no evidence that
      frequency control is superior to rhythm control or vice versa, therapy strategies
      should depend on the clinical status and comorbidities of the individual patient.
      However, adequate anticoagulation for prevention of thromboembolism should be
      performed in every patient, even after conversion of atrial fibrillation into
      sinus rhythm.

PMID- 18629449
TI  - Intrinsic and extrinsic control of effector T cell survival and memory T cell
      development.
AB  - Following infection or vaccination T cells expand exponentially and differentiate
      into effector T cells in order to control infection and coordinate the multiple
      effector arms of the immune system. Soon after this expansion, the majority of
      antigen-specific T cells die to reattain homeostasis and a small pool of memory T
      cells forms to provide long-term immunity to subsequent re-infection. Our
      understanding of how this process is controlled has improved considerably over
      the recent years, but many questions remain outstanding. This review focuses on
      the recent advancements in this area with an emphasis on how the contraction of
      activated T cells is coordinately regulated by a combination of factors extrinsic
      and intrinsic to the activated T cells.

PMID- 18629454
TI  - Ablation of atrial fibrillation: patient selection, techniques, and the results.
AB  - Atrial fibrillation (AF) is a common arrhythmia, affecting an estimated 2 million
      people in the United States and its prevalence increases with age, reaching 10%
      in those > or = 80 years. AF confers a four- to fivefold increased risk of stroke
      compared to the general population and has been associated with a doubling of all
      cause mortality. During the past decade, limited success rates of drug treatment
      stimulated an exploration of interventional treatment options for AF. As our
      knowledge on initiating triggers and perpetuating substrate of AF expanded,
      different potentially curative catheter ablation techniques have been developed.
      In this article we review the current patient selection criteria, methods, and
      the results of the catheter ablation of atrial fibrillation.

PMID- 18629453
TI  - [Catheter ablation of typical atrial flutter].
AB  - Atrial flutter is one of the most common supraventricular arrhythmic diseases and
      occurs with an incidence of 88/100,000. The high risk for thromboembolic events
      is similar to that for atrial fibrillation and also has the risk for fast
      conduction to the ventricle. Pharmacological treatment is not significantly
      effective. Catheter ablation of common atrial flutter offers an alternative with
      a high quality outcome ranging from 90-96% and a low recurrence rate of 2-6%.
      Radiofrequency catheter ablation of the cavotricuspidal isthmus is an established
      treatment for common atrial flutter. Modern techniques like cryo-ablation show
      nearly the same results and will be an alternative to the RF ablation in the
      future.

PMID- 18629455
TI  - [Pulmonary vein isolation in treatment of atrial fibrillation--strategies,
      results and complications].
AB  - Atrial fibrillation is a relevant challenge for health care systems in Europe and
      North America. Interventional treatment of atrial fibrillation in terms of
      ablation of atrial structures including isolation of the pulmonary veins is
      nowadays established as an alternative to drug therapy, especially if treatment
      with antiarrhythmic drugs has been ineffective. Recently published European and
      North American guidelines support this strategy. This article describes different
      techniques of atrial fibrillation ablation including intracardiac echo-guided
      pulmonary vein isolation. Potential complications, success rates and different
      follow-up strategies are specified. Furthermore interventional treatment of
      atrial fibrillation of heart failure patients is discussed.

PMID- 18629456
TI  - [Complications after ablation of supraventricular tachycardias].
AB  - The ablation of supraventricular tachycardias is a curative procedure with high
      success rates. Due to considerably improvement of quality of life, it becomes the
      therapy of first choice in nearly all kinds of symptomatic supraventricular
      reentry tachycardias. Following the guidelines for the management of patients
      with atrial fibrillation, pulmonary vein isolation is still second choice of
      therapy after ineffective medical treatment. In experienced electrophysiological
      centres a complication rate of < 2% and an intention to treat mortality of < 0.1%
      can be expected.

PMID- 18629457
TI  - [17th part: Transvenous pacemaker implantation in corrected Fallot tetralogy with
      heart failure].
AB  - Implantation of transvenous pacemaker leads can be particularly--and unexpectedly
      -difficult in patients with corrected congenital heart disease. If the operation
      has been performed a long time ago, there are frequently no more reports about
      the exact intervention available. The present case illustrates the importance of
      the ECG and fluoroscopy during implantation in complex congenital heart disease.

PMID- 18629458
TI  - Deceleration in maturation of bone during adolescent age in achondroplasia--a
      retrospective study using RUS scoring system.
AB  - OBJECTIVES: Knowledge of bone age in achondroplasia is required for the
      prediction of adult height, timings of limb lengthening, and epiphysiodesis
      procedures. The purpose of this investigation was to determine the differences in
      skeletal age in achondroplasia and a control population with the Tanner
      Whitehouse 3 method using the RUS score and to determine the right age for the
      interventional procedure for limb lengthening procedure or deformity correction
      in these patients. MATERIALS AND METHODS: Left hand radiographs of 34 patients
      (age range, 5-18 years) with achondroplasia were evaluated for skeletal age using
      the RUS scoring system, which were compared with the left hand radiographs of 41
      patients (age range, 5-18 years) without achondroplasia measuring skeletal age.
      The difference in chronological age and RUS bone age were evaluated statistically
      according to gender and age group. RESULTS: In the achondroplasia group,
      chronological age were 10.5 +/- 4.3 years for males and 10.1 +/- 3.6 years for
      females and RUS bone age were 9.2 +/- 4.0 years for males and 8.9 +/- 3.4 years
      for females, which showed statistically significantly difference (males p =
      0.0003 and females p < 0.0001), while in the control group, chronological age
      were 11.1 +/- 2.9 years for males and 10.7 +/- 3.4 years for females and RUS bone
      age were 11.2 +/- 3.4 years for males and 10.7 +/- 3.3 years for females, which
      did not show statistically significantly difference (males p = 0.54 and females p
      = 0.76). Our finding suggested a delay of 1.4 years for males and 1.2 years for
      females in the maturation of bone in achondroplasia patients. Difference between
      chronological age and RUS bone age was 0.9 +/- 1.1 for <10 years and 1.6 +/- 0.9
      for >10 years in the study group, while 0.1 +/- 1.1 for <10 years and -0.2 +/-
      0.6 for >10 years in the control group, which also showed >statistically
      significant difference (<10 years p = 0.04 and >10 years p < 0.0001). These
      differences indicate that there was a delay in the maturation of bones by 1 year
      in the group <10 years and 1.8 years in the group >10 years in achondroplasia
      patients compared to nonachondroplasia patients. CONCLUSION: We recommend the use
      of the Tanner-Whitehouse 3 method especially the radius, ulna, short bone score
      to measure the skeletal age and to wait for a longer time before interventional
      procedures in achondroplasia patients.

PMID- 18629459
TI  - MRI and histological evaluation of the infiltrative growth pattern of
      myxofibrosarcoma.
AB  - OBJECTIVE: Myxofibrosarcoma often shows abnormal signal infiltration along the
      fascial plane on magnetic resonance imaging (MRI). The objective was to describe
      this MRI characteristic of myxofibrosarcoma with pathologic findings for
      comparison. MATERIALS AND METHODS: Clinical, histological, and imaging data for
      21 patients with myxofibrosarcoma were reviewed retrospectively. RESULTS:
      Seventeen tumors showed a diffuse infiltrative pattern on MRI. All tumors with
      diffuse infiltrative growth pattern showed borderless extension of atypical cells
      with moderate nuclear atypia to the muscle fascia. Notably, the remaining four
      patients with focal growth pattern on MRI also demonstrated infiltrative growth
      pattern histologically suggesting that myxofibrosarcoma shows an infiltrative
      growth property even in the lack of infiltrative growth pattern on MRI.
      CONCLUSION: Most myxofibrosarcoma show an infiltrative growth pattern
      histologically. Orthopedic oncologist should pay careful attention to accurately
      assess tumor extension. It seems prudent to resect the entire area of abnormal
      signal extension seen on MRI whenever possible to obtain an adequate surgical
      margin of myxofibrosarcoma.

PMID- 18629460
TI  - Bone marrow edema syndrome.
AB  - Bone marrow edema syndrome (BMES) refers to transient clinical conditions with
      unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH),
      regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD).
      BMES is primarily characterized by bone marrow edema (BME) pattern. The disease
      mainly affects the hip, the knee, and the ankle of middle-aged males. Many
      hypotheses have been proposed to explain the pathogenesis of the disease.
      Unfortunately, the etiology of BMES remains obscure. The hallmark that separates
      BMES from other conditions presented with BME pattern is its self-limited nature.
      Laboratory tests usually do not contribute to the diagnosis. Histological
      examination of the lesion is unnecessary. Plain radiographs may reveal regional
      osseous demineralization. Magnetic resonance imaging is mainly used for the early
      diagnosis and monitoring the progression of the disease. Early differentiation
      from other aggressive conditions with long-term sequelae is essential in order to
      avoid unnecessary treatment. Clinical entities, such as TOH, RMO, and RSD are
      spontaneously resolving, and surgical treatment is not needed. On the other hand,
      early differential diagnosis and surgical treatment in case of osteonecrosis is
      of crucial importance.

PMID- 18629461
TI  - Relationship between mucoid hypertrophy of the anterior cruciate ligament (ACL)
      and morphologic change of the intercondylar notch: MRI and arthroscopy
      correlation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      mucoid hypertrophy of the anterior cruciate ligament (ACL) and morphologic change
      of the intercondylar notch. MATERIALS AND METHODS: We retrospectively reviewed
      the 105 patients with knee magnetic resonance imaging (MRI) with or without knee
      arthroscopy [group 1: patients with arthroscopic notchplasty (N = 47), group 2:
      knee arthroscopy demonstrating intact ACL (N = 33), and group 3: patients with
      normal knee MRI but no arthroscopy (N = 25)]. Groups 2 and 3 served as an
      arthroscopic and MR control group, respectively. Two musculoskeletal radiologists
      reviewed all MR examinations. The intercondylar notch width, notch index (width
      of intercondylar notch/width of femoral condyle), transverse notch angle (TNA),
      sagittal notch angle (SNA), and notch area were recorded on axial and sagittal MR
      images at the midpoint of Blumensaat's line which was identified on sagittal
      images. The diameter of the ACL was recorded on coronal MR images at the
      posterior end of Blumensaat's line. RESULTS: The mean values of the intercondylar
      notch width, notch index, TNA, SNA, notch area, and ACL diameter for the three
      groups were 16.0 mm/0.2/50.3 degrees /36.5 degrees /249.0 mm(2)/7.7 mm (group 1);
      19.3 mm/0.3/52.9 degrees /40.2 degrees /323.4 mm(2)/4.8 mm (group 2); and 20.3
      mm/0.3/51.4 degrees /39.1 degrees /350.8 mm(2)/4.5 mm (group 3). The
      intercondylar notch width, notch index, SNA, and notch area were smaller, and ACL
      diameter was thicker in group 1 compared with the other groups (p < 0.05).
      CONCLUSION: Patients with mucoid ACL hypertrophy show a narrower notch, a steeper
      notch angle, and a smaller notch area than control groups.

PMID- 18629462
TI  - A lethal form of Gorham disease associated with extensive musculoskeletal
      pneumatosis: case report and review of the literature.
AB  - We report here the imaging findings of a rare case of a lethal form of Gorham
      disease in a young female patient. Multimodality imaging findings over 13 year
      follow-up demonstrated progressive wide spread skeletal and soft tissue
      abnormalities with permeative osteolysis, pathological fractures and severe
      skeletal deformities. Unusual extensive osseous and soft tissue pneumatosis was
      illustrated on cross-sectional studies. The progressive nature of this form of
      Gorham disease and the subsequent complications eventually culminated in
      patient's death.

PMID- 18629463
TI  - [The challenge of benign hepatic tumors].

PMID- 18629464
TI  - [Antithrombotic therapy of acute myocardial infarction].
AB  - Inhibition of blood coagulation is an essential cornerstone of the therapy of
      acute myocardial infarction. Risk stratification represents a valuable tool to
      adjust the intensity of anticoagulation and timing of invasive therapy according
      to patient risk. All patients presenting with myocardial infarction should be
      treated with aspirin and clopidogrel. Patients with ST-segment elevation
      myocardial infarction and high-risk patients with myocardial infarction without
      ST-segment elevation who undergo invasive therapy should be treated immediately
      with unfractionated heparin (alternatively enoxaparin) and a glycoprotein (GP)
      IIb/IIIa antagonist in the catheter laboratory. The direct thrombin antagonist
      bivalirudin may emerge as an attractive alternative in these patients. In low
      risk patients who undergo delayed urgent elective interventional therapy the
      factor Xa antagonist fondaparinux may be advantageous because of its low bleeding
      rate. In these patients administration of unfractionated heparin is necessary for
      percutaneous coronary intervention.

PMID- 18629465
TI  - [Therapy of acute myocardial infarction in the prehospital setting].
AB  - The time period from symptom onset to hospital admission is of outstanding
      importance for the prognosis of a patient with an acute myocardial infarction. He
      is threatened by sudden cardiac death triggered by ventricular fibrillation on
      the one hand and on the other hand this period offers the chance for a timely
      decision on the optimal reperfusion strategy. A broad spectrum of therapeutic
      opportunities regarding thrombolysis, antiplatelets and anticoagulation has been
      proven to be effective in large randomised trials and registries. These results
      should influence the individual decision on reperfusion treatment as well as the
      patient's conditions, time lines, logistics and local resources.

PMID- 18629467
TI  - Genetic association of ETHYLENE-INSENSITIVE3-like sequence with the sex
      determining M locus in cucumber (Cucumis sativus L.).
AB  - Cucumber (Cucumis sativus L.) has served as the model system for sex expression
      in flowering plants and its sex type is predominantly controlled by two genetic
      loci, F and M. Ethylene is the major plant hormone that regulates sex expression
      in cucumber. The current model predicts that ethylene serves as both a promoter
      of femaleness via the F locus and an inhibitor of the male sex via the M locus.
      In support of this model, genetic, genomic, and transcript analyses indicate that
      the F gene encodes a key enzyme in ethylene biosynthesis. In this study, we
      discovered that the M locus co-segregates with an ETHYLENE-INSENSITIVE3 (EIN3)
      like genomic sequence in an F2 population of 96 individuals. This genetic
      association agrees with the prediction that the M locus is involved in ethylene
      signaling, thus providing another line of evidence in favor of the model. In
      addition, we generated an amplified fragment length polymorphism (AFLP) map of
      the M locus, which was delimited into a genetic interval of 2.5 cM. The genetic
      association and the local map will assist the molecular isolation of the M gene
      using the combination of positional cloning and candidate gene approach.

PMID- 18629468
TI  - [Short-term results after STAR total ankle replacement].
AB  - BACKGROUND: This retrospective study was performed to investigate the clinical
      and radiological results after STAR total ankle replacement. MATERIAL AND
      METHODS: Between January 2000 and September 2004, 49 patients with an average age
      of 62.5 years underwent total ankle replacement with the STAR prosthesis. At an
      average follow-up of 30.4 months, 48 patients were examined clinically and
      radiologically. The Kofoed ankle score and the patients' subjective satisfaction
      were evaluated. RESULTS: The operation improved the Kofoed ankle score
      significantly, from 28 to 86 points, 90% of the patients were satisfied with the
      results. The revision rate was 10%. CONCLUSION: The early results after
      implantation of the STAR ankle prosthesis are encouraging. With correct
      indication, a high rate of pain reduction and patient satisfaction can be
      achieved. The long-term benefit of this procedure has yet to be determined.

PMID- 18629466
TI  - Adult stem cells and their trans-differentiation potential--perspectives and
      therapeutic applications.
AB  - Stem cells are self-renewing multipotent progenitors with the broadest
      developmental potential in a given tissue at a given time. Normal stem cells in
      the adult organism are responsible for renewal and repair of aged or damaged
      tissue. Adult stem cells are present in virtually all tissues and during most
      stages of development. In this review, we introduce the reader to the basic
      information about the field. We describe selected stem cell isolation techniques
      and stem cell markers for various stem cell populations. These include makers for
      endothelial progenitor cells (CD146/MCAM/MUC18/S-endo-1, CD34, CD133/prominin,
      Tie-2, Flk1/KD/VEGFR2), hematopoietic stem cells (CD34, CD117/c-Kit, Sca1),
      mesenchymal stem cells (CD146/MCAM/MUC18/S-endo-1, STRO-1, Thy-1), neural stem
      cells (CD133/prominin, nestin, NCAM), mammary stem cells (CD24, CD29, Sca1), and
      intestinal stem cells (NCAM, CD34, Thy-1, CD117/c-Kit, Flt-3). Separate section
      provides a concise summary of recent clinical trials involving stem cells
      directed towards improvement of a damaged myocardium. In the last part of the
      review, we reflect on the field and on future developments.

PMID- 18629469
TI  - NAVA: brain over machine?

PMID- 18629470
TI  - Protein C concentrate in adult septic patients.

PMID- 18629471
TI  - Physiologic response to varying levels of pressure support and neurally adjusted
      ventilatory assist in patients with acute respiratory failure.
AB  - OBJECTIVE: Neurally adjusted ventilatory assist (NAVA) is a new mode wherein the
      assistance is provided in proportion to diaphragm electrical activity (EAdi). We
      assessed the physiologic response to varying levels of NAVA and pressure support
      ventilation (PSV). SETTING: ICU of a University Hospital. PATIENTS: Fourteen
      intubated and mechanically ventilated patients. DESIGN AND PROTOCOL: Cross-over,
      prospective, randomized controlled trial. PSV was set to obtain a VT/kg of 6-8
      ml/kg with an active inspiration. NAVA was matched with a dedicated software. The
      assistance was decreased and increased by 50% with both modes. The six assist
      levels were randomly applied. MEASUREMENTS: Arterial blood gases (ABGs), tidal
      volume (VT/kg), peak EAdi, airway pressure (Paw), neural and flow-based timing.
      Asynchrony was calculated using the asynchrony index (AI). RESULTS: There was no
      difference in ABGs regardless of mode and assist level. The differences in
      breathing pattern, ventilator assistance, and respiratory drive and timing
      between PSV and NAVA were overall small at the two lower assist levels. At the
      highest assist level, however, we found greater VT/kg (9.1 +/- 2.2 vs. 7.1 +/- 2
      ml/kg, P < 0.001), and lower breathing frequency (12 +/- 6 vs. 18 +/- 8.2, P <
      0.001) and peak EAdi (8.6 +/- 10.5 vs. 12.3 +/- 9.0, P < 0.002) in PSV than in
      NAVA; we found mismatch between neural and flow-based timing in PSV, but not in
      NAVA. AI exceeded 10% in five (36%) and no (0%) patients with PSV and NAVA,
      respectively (P < 0.05). CONCLUSIONS: Compared to PSV, NAVA averted the risk of
      over-assistance, avoided patient-ventilator asynchrony, and improved patient
      ventilator interaction.

PMID- 18629472
TI  - Enhanced fluid management with continuous venovenous hemofiltration in pediatric
      respiratory failure patients receiving extracorporeal membrane oxygenation
      support.
AB  - BACKGROUND/PURPOSE: Children receiving extracorporeal membrane oxygenation (ECMO)
      for respiratory failure can have significant fluid overload and renal
      insufficiency. Addition of inline continuous venovenous hemofiltration (CVVH)
      could provide additional benefits in fluid management compared to use of standard
      medical therapies with ECMO. METHODS: Patients with pediatric respiratory failure
      receiving ECMO with CVVH were case-matched to similar patients receiving ECMO
      without CVVH to compare fluid balance, medication use, and clinical outcomes.
      RESULTS: Twenty-six of eighty-six patients with pediatric respiratory failure on
      ECMO (30%) received CVVH for >24 h (median 7.5 days on CVVH). Survival was not
      significantly different between patients receiving CVVH and those who did not
      receive CVVH (P = 0.51). For ECMO survivors receiving CVVH, overall fluid balance
      was less than that in non-CVVH survivors (median 25.1 ml kg(-1) day(-1); range 
      40.2 to 71.2 vs. 40.2, 1.1 to 134.9; P = 0.028). Time to desired caloric intake
      was faster in patients receiving CVVH (1 day, 1-5) than in patients who did not
      receive CVVH (5 days; 1-11; P < 0.001). Patients receiving CVVH-ECMO also
      received less furosemide (0.67 vs. 2.11 mg kg(-1) day(-1); P = 0.009).
      CONCLUSIONS: Use of CVVH in ECMO was associated with improved fluid balance and
      caloric intake and less diuretics than in case-matched ECMO controls.

PMID- 18629473
TI  - Characterization of two TonB systems in marine fish pathogen Vibrio
      alginolyticus: their roles in iron utilization and virulence.
AB  - In Gram-negative bacteria, the TonB/ExbB/ExbD complex is required to energize the
      specific high-affinity receptors mediating iron uptake processes. In fish
      pathogen Vibrio alginolyticus MVP01, which exhibited capacities to scavenge iron
      sources with various specific iron uptake systems, we identified and
      characterized two sets of TonB systems. In V. alginolyticus, TonB1 and TonB2
      systems were arrayed as TonB1-ExbB1-ExbD1 and ExbB2-ExbD2-TonB2, respectively.
      The transcription of the TonB systems was regulated by the iron concentration in
      culture medium. While TonB1 system specifically contributed to the hemin and
      hemoglobin utilization in V. alginolyticus MVP01, both of the TonB systems showed
      abilities to support the utilization of iron sources from ferrichrome and
      vibrioferrin, the endogenous siderophore of V. alginolyticus. In addition, when
      mutants of the TonB systems were inoculated intraperitoneally into the fish
      Brachydanio rerio, marked attenuation in virulence of V. alginolyticus was
      observed, indicating that both of the TonB systems are essential for the
      virulence of V. alginolyticus.

PMID- 18629475
TI  - Characterization and phylogenetic analysis of ectoine biosynthesis genes from
      Bacillus halodurans.
AB  - Ectoine, a cyclic tetrahydropyrimidine (2-methyl-1,4,5,6-tetrahydropyrimidine-4
      carboxylic acid), is a natural compound, which serves as a protective substance
      in many bacterial cells. In this study, the putative ectABC gene cluster from
      Bacillus halodurans was heterologously expressed in E. coli and the production of
      ectoine was confirmed by HPLC analysis. The activity of the enzymes coded by the
      ectA, B and C genes were found to be higher in induced transgenic cells compared
      to the uninduced cells. Phylogenetic analysis revealed sequence identities
      ranging from 36-73% for ectA gene, 55-81% for ectB gene and 55-80% for ectC gene
      indicating that the enzymes are evolutionarily well conserved.

PMID- 18629474
TI  - An N-acyl homolog of mycothiol is produced in marine actinomycetes.
AB  - Marine actinomycetes have generated much recent interest as a potentially
      valuable source of novel antibiotics. Like terrestrial actinomycetes the marine
      actinomycetes are shown here to produce mycothiol as their protective thiol.
      However, a novel thiol, U25, was produced by MAR2 strain CNQ703 upon progression
      into stationary phase when secondary metabolite production occurred and became
      the dominant thiol. MSH and U25 were maintained in a reduced state during early
      stationary phase, but become significantly oxidized after 10 days in culture.
      Isolation and structural analysis of the monobromobimane derivative identified
      U25 as a homolog of mycothiol in which the acetyl group attached to the nitrogen
      of cysteine is replaced by a propionyl residue. This N-propionyl-desacetyl
      mycothiol was present in 13 of the 17 strains of marine actinomycetes examined,
      including five strains of Salinispora and representatives of the MAR2, MAR3, MAR4
      and MAR6 groups. Mycothiol and its precursor, the pseudodisaccharide 1-O-(2-amino
      2-deoxy-alpha-D-glucopyranosyl)-D-myo-inositol, were found in all strains. High
      levels of mycothiol S-conjugate amidase activity, a key enzyme in mycothiol
      dependent detoxification, were found in most strains. The results demonstrate
      that major thiol/disulfide changes accompany secondary metabolite production and
      suggest that mycothiol-dependent detoxification is important at this
      developmental stage.

PMID- 18629476
TI  - Effect of calmidazolium on [Ca2+]i and viability in human hepatoma cells.
AB  - The effect of calmidazolium on cytosolic free Ca2+ concentrations ([Ca2+]i) and
      viability has not been explored in human hepatoma cells. This study examined
      whether calmidazolium altered [Ca2+]i and caused cell death in HA59T cells.
      [Ca2+]i and cell viability were measured using the fluorescent dyes fura-2 and
      WST-1, respectively. Calmidazolium at concentrations > or =1 microM increased
      [Ca2+]i in a concentration-dependent manner with an EC50 value of 1.5 microM. The
      Ca2+ signal was reduced partly by removing extracellular Ca2+. Calmidazolium
      induced Mn2+ quench of fura-2 fluorescence implicating Ca2+ influx. The Ca2+
      influx was insensitive to L-type Ca2+ entry blockers, but was inhibited partly by
      enhancing or inhibiting protein kinase C activity. In Ca2+-free medium, after
      pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump
      inhibitor), calmidazolium-induced [Ca2+]i rises were largely inhibited; and
      conversely, calmidazolium pretreatment totally suppressed thapsigargin-induced
      [Ca2+]i rises. Inhibition of phospholipase C with 2 microM U73122 did not change
      calmidazolium-induced [Ca2+]i rises. At concentrations between 1 and 15 microM,
      calmidazolium induced apoptosis-mediated cell death. Collectively, in HA59T
      hepatoma cells, calmidazolium induced [Ca2+]i rises by causing Ca2+ release from
      the endoplasmic reticulum in a phospholipase C-independent manner, and Ca2+
      influx via protein kinase C-regulated Ca2+ entry pathway. Calmidazolium caused
      cytotoxicity via apoptosis.

PMID- 18629479
TI  - The characterization of paintings: some key research issues.

PMID- 18629477
TI  - Profiling of behavioral changes and hippocampal gene expression in mice
      chronically treated with the SSRI paroxetine.
AB  - INTRODUCTION: Monoamine-based antidepressants inhibit neurotransmitter reuptake
      within short time. However, it commonly takes several weeks until clinical
      symptoms start to resolve--indicating the involvement of effects distant from
      reuptake inhibition. OBJECTIVE: To unravel other mechanisms involved in drug
      action, a "reverse" pharmacological approach was applied to determine
      antidepressant-induced alterations of hippocampal gene expression. MATERIALS AND
      METHODS: The behavioral response to long-term paroxetine administration of male
      DBA/2Ola mice was assessed by the forced swim test (FST), the modified hole board
      (mHB), and the dark/light box. Hippocampi of test-naive mice were dissected, and
      changes in gene expression by paroxetine treatment were investigated by means of
      microarray technology. RESULTS AND DISCUSSION: Robust effects of paroxetine on
      passive stress-coping behavior in the FST were observed. Furthermore, anxiolytic
      properties of long-term antidepressant treatment could be identified in DBA mice
      in both, the mHB and dark/light box. Analysis of microarray results revealed a
      list of 60 genes differentially regulated by chronic paroxetine treatment.
      Preproenkephalin 1 and inhibin beta-A showed the highest level of transcriptional
      change. Furthermore, a number of candidates involved in
      neuroplasticity/neurogenesis emerged (e.g., Bdnf, Gfap, Vim, Sox11, Egr1, Stat3).
      Seven selected candidates were confirmed by in situ hybridization. Additional
      immunofluorescence colocalization studies of GFAP and vimentin showed more
      positive cells to be detected in long-term paroxetine-treated DBA mice.
      CONCLUSION: Candidate genes identified in the current study using a mouse strain
      validated for its responsiveness to long-term paroxetine treatment add, in our
      opinion, to unraveling the mechanism of action of paroxetine as a representative
      for SSRIs.

PMID- 18629480
TI  - Precision-cut liver slices from rats of different ages: basal cytochrome P450
      dependent monooxygenase activities and inducibility.
AB  - The biotransformation capacity - of the cytochrome P450 (CYP) system for example 
      is lower but inducibility is more pronounced in neonates than in adults. On the
      other hand, both enzyme activities and inducibility decline with senescence.
      Precision-cut rat liver slices are widely used as an in vitro tool for the
      examination of drug toxicity, xenobiotic metabolism or enzyme induction. The aim
      of the present study was to assess whether age-related changes in CYP activities
      and induction observed in vivo are also mirrored in vitro in liver slices. For
      this purpose, different CYP model reactions were measured in precision-cut liver
      slices from one-day-old, 40-day-old and one-year-old rats after in vitro exposure
      to various inducers. Similar to the in vivo situation, basal CYP activities were
      distinctly lower and inducibility was much more pronounced in liver slices from
      neonatal than in those from adult animals. Also, enzyme activities were mostly
      somewhat lower in liver slices from aged rats compared to those from 40-day-old
      rats. However, CYP inducibility was less pronounced than with younger animals
      too. Thus, precision-cut rat liver slices are a suitable in vitro tool for
      investigating age-related changes in CYP activities and induction as well as
      developmental differences in drug metabolism and toxicity.

PMID- 18629482
TI  - Developmental changes in the dynamical structure of postural sway during a
      precision fitting task.
AB  - Recent research using measures to assess the time-dependent structure of postural
      fluctuations has provided new insights into the stability and adaptability of
      human postural control in adults. To date, little research has examined how
      postural dynamics reflecting the stability and adaptability of postural control
      may change as a function of development, especially during supra-postural tasks.
      The goal of this study was to examine the dynamics of postural fluctuations
      during a manual-fitting task in which precision, visual and postural task
      constraints were altered in children and adults. Three age groups were tested: 7
      , 10-year olds and college aged adults. Recurrence quantification analysis (RQA)
      was used to assess the regularity (percent determinism) and complexity (entropy)
      of the center of pressure (CoP) in the anterior-posterior (AP) and medial-lateral
      (ML) directions. The CoP patterns exhibited by adults were more deterministic and
      more complex (higher entropy) than those of the 7-year-old children under the
      different experimental manipulations. No differences between the adults and the
      10-year-old children were observed. The increase in determinism with a
      corresponding increase in entropy exhibited by the adults and older-children
      during a manual fitting task may be a prospective mechanism over which postural
      movements follow a more predictable path allowing for stable and flexible task
      performance. Our results also support the notion that complex postural
      fluctuations (as measured by RQA entropy) are functional and typically increase
      as the precision requirements of a manual task increase.

PMID- 18629483
TI  - Electroencephalographic correlates of target and outcome errors.
AB  - Different neural systems underlie the evaluation of different types of errors.
      Recent electroencephalographic evidence suggests that outcome errors -- errors
      indicating the failure to achieve a movement goal -- are evaluated within medial
      frontal cortex (Krigolson and Holroyd 2006, 2007a, b). Conversely, evidence from
      a variety of manual aiming studies has demonstrated that target errors --
      discrepancies between the actual and desired motor command brought about by an
      unexpected change in the movement environment -- are mediated within posterior
      parietal cortex (e.g., Desmurget et al. 1999, 2001; Diedrichsen et al. 2005).
      Here, event-related brain potentials (ERP) were recorded to assess medial-frontal
      and parietal ERP components associated with the evaluation of outcome and target
      errors during performance of a manual aiming task. In line with previous results
      (Krigolson and Holroyd 2007a), we found that target perturbations elicited an ERP
      component with a parietal scalp distribution, the P300. However, the timing of
      kinematic changes associated with accommodation of the target perturbations
      relative to the timing of the P300 suggests that the P300 component was not
      related to the online control of movement. Instead, we believe that the P300
      evoked by target perturbations reflects the updating of an internal model of the
      movement environment. Our results also revealed that an error-related negativity,
      an ERP component typically associated with the evaluation of speeded response
      errors and error feedback, was elicited when participants missed the movement
      target. Importantly, this result suggests that a reinforcement learning system
      within medial-frontal cortex may play a role in improving subsequent motor
      output.

PMID- 18629485
TI  - Fluid sign in the treated bodies after percutaneous vertebroplasty.
AB  - INTRODUCTION: The aims of this study are to describe non-healing in the treated
      vertebral body after percutaneous vertebroplasty and analyze the influence of
      vacuum cleft, location, and severity of collapse on the development of nonunion
      cement. MATERIALS AND METHODS: Of 208 patients (266 treated vertebral bodies) who
      were treated with percutaneous vertebroplasty from September 2002 to May 2006, 23
      patients (41 treated levels) with residual or recurrent pain underwent follow-up
      magnetic resonance imaging (MRI) study. Retrospective chart review with analysis
      of preoperative and postoperative MRIs were performed in these 23 patients.
      RESULTS: In the 41 treated vertebral bodies, 22 of 41 bodies had vacuum cleft
      found in the preoperative MRI study. Eight of the 22 treated vertebral bodies
      with preoperative vacuum clefts were found to have fluid between the interface of
      cement and the residual bone in the collapsed vertebral bodies on follow-up MRI.
      The adjacent discs of these treated vertebral bodies were upward/downward
      displaced. The endplate of the adjacent vertebral body exhibited fibrotic change.
      Treated bodies with vacuum clefts and level A location (T9, T11, T12, and L1) had
      higher probability of developing nonunion of the cement with statistical
      significance. The probability of nonunion cement in severe collapsed bodies might
      be higher than that of union cement in mild collapsed ones, but was not
      statistically significant. CONCLUSIONS: Fluid sign in the treated body represents
      unhealed bone-cement interface. The location of the treated vertebral body and
      existence of vacuum cleft in the treated bodies may be important factors
      influencing the nonunion of cement.

PMID- 18629484
TI  - Avoiding moving obstacles.
AB  - To successfully move our hand to a target, we must consider how to get there
      without hitting surrounding objects. In a dynamic environment this involves being
      able to respond quickly when our relationship with surrounding objects changes.
      People adjust their hand movements with a latency of about 120 ms when the
      visually perceived position of their hand or of the target suddenly changes. It
      is not known whether people can react as quickly when the position of an obstacle
      changes. Here we show that quick responses of the hand to changes in obstacle
      position are possible, but that these responses are direct reactions to the
      motion in the surrounding. True adjustments to the changed position of the
      obstacle appeared at much longer latencies (about 200 ms). This is even so when
      the possible change is predictable. Apparently, our brain uses certain
      information exceptionally quickly for guiding our movements, at the expense of
      not always responding adequately. For reaching a target that changes position,
      one must at some time move in the same direction as the target did. For avoiding
      obstacles that change position, moving in the same direction as the obstacle is
      not always an adequate response, not only because it may be easier to avoid the
      obstacle by moving the other way, but also because one wants to hit the target
      after passing the obstacle. Perhaps subjects nevertheless quickly respond in the
      direction of motion because this helps avoid collisions when pressed for time.

PMID- 18629486
TI  - CT findings of plastic bronchitis in children after a Fontan operation.
AB  - BACKGROUND: Plastic bronchitis is a rare cause of acute obstructive respiratory
      failure in children. Life-threatening events are much more frequent in patients
      with repaired cyanotic congenital heart disease, and most frequent following a
      Fontan operation. Commonly, the diagnosis is not made until bronchial casts are
      expectorated. Detailed CT findings in plastic bronchitis have not been described.
      OBJECTIVE: To describe the CT findings in plastic bronchitis in children after a
      Fontan operation. MATERIALS AND METHODS: Three children with plastic bronchitis
      after a Fontan operation were evaluated by chest CT. Bronchial casts were
      spontaneously expectorated and/or extracted by bronchoscopy. Airway and lung
      abnormalities seen on CT were analyzed in the three children. RESULTS: CT
      demonstrated bronchial casts in the central airways with associated atelectasis
      and consolidation in all children. The affected airways were completely or
      partially obstructed by the bronchial casts without associated bronchiectasis.
      The airway and lung abnormalities rapidly improved after removal of the bronchial
      casts. CONCLUSION: CT can identify airway and lung abnormalities in children with
      plastic bronchitis after a Fontan operation. In addition, CT can be used to guide
      bronchoscopy and to monitor treatment responses, and thereby may improve clinical
      outcomes.

PMID- 18629487
TI  - Severe acute haemorrhagic liver failure in a neonate with a favourable
      spontaneous outcome.
AB  - Acute liver failure in neonates is rare and is frequently associated with an
      unfavourable outcome. There is no curative treatment other than liver
      transplantation. Screening for viral, metabolic, toxic or vascular disease is
      essential to assess the prognosis and to guide specific treatment. Hepatic
      haemorrhage in neonates is often associated with bacterial infection, trauma and
      coagulopathies. We present a unique case of neonatal acute liver failure and
      multifocal massive haemorrhagic intrahepatic lesions of traumatic origin,
      documented by US and MRI. The patient made a spontaneous recovery. Clinical,
      biological and imaging outcome was excellent despite the apparent severity of the
      initial features. The only possible aetiology was a difficult caesarean delivery
      for mild fetal macrosomia.

PMID- 18629488
TI  - Suppressive effect of Elf-1 on FcepsilonRI alpha-chain expression in primary mast
      cells.
AB  - The high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, is
      specifically expressed in mast cells and basophils and plays a key role in IgE
      mediated allergic reactions. The transcription factor Elf-1 has been previously
      identified to bind to the promoter of the human FcepsilonRI alpha-chain, which is
      essential for the function and expression of FcepsilonRI. In the present study,
      Elf-1 siRNA was conducted to evaluate the effects of Elf-1 on FcepsilonRI alpha
      chain expression in the primary mouse mast cells, bone marrow-derived mast cells
      (BMMC). Introduction of Elf-1 siRNA effectively reduced expression levels of Elf
      1 mRNA and protein in BMMC. Transient reporter assay showed that the knockdown of
      Elf-1 by siRNA resulted in increased FcepsilonRI alpha-chain promoter activity,
      while overexpression of Elf-1 suppressed alpha-chain promoter activity in BMMC.
      Elf-1 siRNA-treated BMMC exhibited marked upregulation of FcepsilonRI alpha-chain
      transcription, whereas beta-chain mRNA was not affected by Elf-1 siRNA. Chromatin
      immunoprecipitation assay showed that the amount of transcription factor PU.1,
      recognizing the cis-element close to the Elf-1-site on the FcepsilonRI alpha
      chain promoter, was significantly increased by introduction of Elf-1 siRNA. These
      results indicate that Elf-1 negatively regulates FcepsilonRI alpha-chain
      expression by suppressing PU.1-mediated transcription of the alpha-chain in BMMC.

PMID- 18629489
TI  - Rapid high-resolution MHC class I genotyping of Chinese rhesus macaques by
      capillary reference strand-mediated conformational analysis.
AB  - Rhesus macaques (Macaca mulatta) provide well-established models for studying
      human disease pathogenesis and vaccine development. When challenged with
      infectious agents, macaques exhibit individual differences in susceptibility. An
      important determinant of these differences is the complement of major
      histocompatability complex (MHC) class I sequences expressed by each animal.
      Although previous studies have reported strong associations between MHC
      expression and disease outcome, a rapid, cost-effective method for high
      resolution MHC genotyping in macaques is lacking. In this study, we adapted a
      modified heteroduplex assay, reference strand-mediated conformational analysis
      (RSCA) to an ABI 3130xl capillary electrophoresis genetic analyzer for macaque
      MHC class I genotyping. For validation, we investigated the concordance of RSCA
      genotyping for 14 MHC class I sequences in 12 Chinese rhesus macaques whose
      genotypes were established through complementary DNA cloning and sequencing of
      MHC class I sequences. We observed a concordance greater than 98% between RSCA
      and the cloning and sequencing data. Furthermore, RSCA confirmed the presence of
      MHC haplotype sharing between three macaques as predicted previously by
      microsatellite analysis. RSCA genotyping of an additional 25 Chinese rhesus
      macaques demonstrated that the frequency of these 14 MHC class I sequences ranged
      from 5% to 32%, with the Mamu-A1*2601 sequence being most common in this cohort.
      Capillary RSCA genotyping has the potential to enable researchers to rapidly
      evaluate MHC class I genotypes in rhesus macaques and associate specific MHC
      sequences with disease susceptibility.

PMID- 18629490
TI  - Vinyl ketone reduction by three distinct Gluconobacter oxydans 621H enzymes.
AB  - Three cytosolic NADPH-dependent flavin-associated proteins (Gox2107, Gox0502, and
      Gox2684) from Gluconobacter oxydans 621H were overproduced in Escherichia coli,
      and the recombinant enzymes were purified and characterized. Apparent native
      molecular masses of 65.2, 78.2, and 78.4 kDa were observed for Gox2107, Gox0502,
      and Gox2684, corresponding to a trimeric structure for Gox2107 and dimers for
      Gox0502 and Gox2684. Analysis of flavin content revealed Gox2107 was flavin
      adenine dinucleotide dependent, whereas Gox0502 and Gox2684 contained flavin
      mononucleotide. The enzymes were able to reduce vinyl ketones and quinones,
      reducing the olefinic bond of vinyl ketones as shown by (1)H nuclear magnetic
      resonance. Additionally, Gox0502 and Gox2684 stereospecifically reduced 5S-(+)
      carvone to 2R,5S-dihydrocarvone. All enzymes displayed highest activities with 3
      butene-2-one and 1,4-naphthoquinone. Gox0502 and Gox2684 displayed a broader
      substrate spectrum also reducing short-chain alpha-diketones, whereas Gox2107 was
      most catalytically efficient.

PMID- 18629491
TI  - The conversion of BTEX compounds by single and defined mixed cultures to medium
      chain-length polyhydroxyalkanoate.
AB  - Here, we report the use of petrochemical aromatic hydrocarbons as a feedstock for
      the biotechnological conversion into valuable biodegradable plastic polymers-
      polyhydroxyalkanoates (PHAs). We assessed the ability of the known Pseudomonas
      putida species that are able to utilize benzene, toluene, ethylbenzene, p-xylene
      (BTEX) compounds as a sole carbon and energy source for their ability to produce
      PHA from the single substrates. P. putida F1 is able to accumulate medium-chain
      length (mcl) PHA when supplied with toluene, benzene, or ethylbenzene. P. putida
      mt-2 accumulates mcl-PHA when supplied with toluene or p-xylene. The highest
      level of PHA accumulated by cultures in shake flask was 26% cell dry weight for
      P. putida mt-2 supplied with p-xylene. A synthetic mixture of benzene, toluene,
      ethylbenzene, p-xylene, and styrene (BTEXS) which mimics the aromatic fraction of
      mixed plastic pyrolysis oil was supplied to a defined mixed culture of P. putida
      F1, mt-2, and CA-3 in the shake flasks and fermentation experiments. PHA was
      accumulated to 24% and to 36% of the cell dry weight of the shake flask and
      fermentation grown cultures respectively. In addition a three-fold higher cell
      density was achieved with the mixed culture grown in the bioreactor compared to
      shake flask experiments. A run in the 5-l fermentor resulted in the utilization
      of 59.6 g (67.5 ml) of the BTEXS mixture and the production of 6 g of mcl-PHA.
      The monomer composition of PHA accumulated by the mixed culture was the same as
      that accumulated by single strains supplied with single substrates with 3
      hydroxydecanoic acid occurring as the predominant monomer. The purified polymer
      was partially crystalline with an average molecular weight of 86.9 kDa. It has a
      thermal degradation temperature of 350 degrees C and a glass transition
      temperature of -48.5 degrees C.

PMID- 18629492
TI  - High-level expression of his-tagged clostridial collagenase in Clostridium
      perfringens.
AB  - Clostridium histolyticum collagenase is used to isolate cells from various organs
      and tissues for tissue engineering, and also to treat destructive fibrosis; thus,
      the demand for high-grade enzyme preparations is increasing. In this study, we
      constructed a plasmid encoding C. histolyticum type II collagenase (ColH) with a
      C-terminal hexahistidine tag (ColH-his) to facilitate the purification of the
      enzyme through immobilized metal affinity chromatography (IMAC). When ColH-his
      was expressed in a protease-deficient mutant of Clostridium perfringens, it was
      produced in the culture supernatant more efficiently than the untagged ColH. ColH
      his exhibited the same hydrolytic activity as ColH against 4-phenylazobenzyloxy
      carbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz peptide), a synthetic collagenase substrate.
      From 100 ml of the culture supernatant, approximately 1 mg of ColH-his was
      purified by ammonium sulfate precipitation, IMAC, and high-performance liquid
      chromatography on a MonoQ column. When IMAC was performed on chelating Sepharose
      charged with Zn(2+) instead of Ni(2+), a potential carcinogenic metal, the
      specific activities against Pz peptide and type I collagen decreased slightly.
      However, they were comparable to those reported for other recombinant ColHs and a
      commercial C. histolyticum collagenase preparation, suggesting that this
      expression system is useful for large-scale preparation of high-grade clostridial
      collagenases.

PMID- 18629493
TI  - Evaluation of ergosterol and its esters in the pileus, gill, and stipe tissues of
      agaric fungi and their relative changes in the comminuted fungal tissues.
AB  - A gradient reversed-phase high-performance liquid chromatography (HPLC) method
      was developed for the rapid determination of free ergosterol, ergosteryl esters,
      and ergocalciferol. The HPLC method was used to evaluate the distribution of
      ergosterol and ergosteryl esters in the different parts (stipe, pileus, and
      gills) of the agaric fungi, Agrocybe aegerita, Termitomyces albuminosus, and
      Lentinus edodes, and the relative changes of free and esterified ergosterols
      during the degradation of ergosterol in the comminuted fungal tissues. The
      results showed that total ergosterol levels and the relative abundances of free
      to esterified ergosterols were different among the various species and in the
      different parts of these agaric fungi. The results also indicated that ergosteryl
      esters were more stable than free ergosterol. While the content of free
      ergosterol markedly decreased, substantial amounts of ergosteryl esters remained
      for a long period, and even an increase in the contents of ergosteryl esters was
      also found in some comminuted fungal tissues. Therefore, it is possible that free
      ergosterol in the cell membrane of the dead fungal hyphae undergoes degradation
      or esterification, by which excess free ergosterol may be removed, and stored in
      cytosolic lipid particles. It is suggested that free ergosterol (not total
      ergosterol) should be used as a biomarker for fungal biomass.

PMID- 18629494
TI  - Expression of a heterologous xylose transporter in a Saccharomyces cerevisiae
      strain engineered to utilize xylose improves aerobic xylose consumption.
AB  - The goal of this investigation was to determine the effect of a xylose transport
      system on glucose and xylose co-consumption as well as total xylose consumption
      in Saccharomyces cerevisiae. We expressed two heterologous transporters from
      Arabidopsis thaliana in recombinant xylose-utilizing S. cerevisiae cells. Strains
      expressing the heterologous transporters were grown on glucose and xylose
      mixtures. Sugar consumption rates and ethanol concentrations were determined and
      compared to an isogenic control strain lacking the A. thaliana transporters.
      Expression of the transporters increased xylose uptake and xylose consumption up
      to 46% and 40%, respectively. Xylose co-consumption rates (prior to glucose
      depletion) were also increased by up to 2.5-fold compared to the control strain.
      Increased xylose consumption correlated with increased ethanol concentration and
      productivity. During the xylose/glucose co-consumption phase, strains expressing
      the transporters had up to a 70% increase in ethanol production rate. It was
      concluded that in these strains, xylose transport was a limiting factor for
      xylose utilization and that increasing xylose/glucose co-consumption is a viable
      strategy for improving xylose fermentation.

PMID- 18629495
TI  - NK cells are migrated and indispensable in the anti-tumor activity induced by
      CCL27 gene therapy.
AB  - Natural killer (NK) cells have been demonstrated could play an important role in
      the treatment of a number of tumors in mice. In the present study, chemokine
      CCL27, which be considered only selectively chemoattracts cutaneous lymphocyte
      antigen positive memory T cells and Langerhans cells, firstly demonstrated that
      it could induce the accumulation of NK cells into tumor by the intratumoral
      injection of CCL27-encoding fiber-mutant vector, AdRGD-CCL27. Experiments using
      spleen cell fractionation and RT-PCR showed CCL27 receptor, mCCR10, was strongly
      expressed in NK cells, suggesting the accumulation of NK cells in tumor was
      attributed to chemoattractant activity of CCL27 itself. Moreover, the combination
      of AdRGD-CCL27 and AdRGD-IL-12 induced the synergistic anti-tumor activity via NK
      dependent manner and induced more NK cells infiltration into tumor nodule than
      that induced by AdRGD-CCL27 alone or AdRGD-IL-12 alone.

PMID- 18629496
TI  - Comment on Shevtsov and Danilkin: Application of external fixation for management
      of hand syndactyly.

PMID- 18629497
TI  - Prosthetic replacement of elbow in postburn bony ankylosis: long-term results.
AB  - Fifteen patients with 17 post-burn bony ankylosed elbows (two bilateral) fixed at
      a mean of 72.5 degrees +/- 27.5 degrees flexion were treated with Baksi sloppy
      hinge elbow arthroplasty. All patients agreed to avoid strenuous use of their
      replaced elbows. There were four males and 11 females whose ages varied from 21
      to 48 years (average 31.6 years). One of the five patients who had severe
      anterior skin contracture required release. One patient died during the early
      follow-up period. During the follow-up studies which ranged from 11 to 23 years
      (average 14.1), eleven patients (68.7%) regained painless stable motion with mean
      recovery of arc of flexion from 20 degrees +/-10 degrees to 107.5 degrees +/-17.5
      degrees with mean range of flexion 90 degrees +/-20 degrees . Good forearm motion
      was retained in all cases. According to the assessment score (Morrey BF, The
      elbow and it's disorder, 2nd edn. W.B. Saunders, Philadelphia, 1993), nine
      (56.2%) patients were recorded as excellent, two (12.5%) as good, and five
      (31.5%) as poor who were considered as failures. The five failures required
      removal of the prosthesis but retained acceptable elbow function due to
      periprosthetic fibrosis connecting the adjacent bone ends.

PMID- 18629498
TI  - Long-term management of thrombocytosis in essential thrombocythaemia.
AB  - Essential thrombocythaemia (ET) is an acquired myeloproliferative disorder with a
      prolonged clinical course and a near-normal life expectancy. Therapy is
      stratified according to risk of thrombohaemorrhagic events. In high-risk
      patients, platelet reduction is generally recommended. In intermediate-risk
      patients, therapy should be considered depending on the severity of associated
      risk factors, especially cardiovascular. In low-risk patients, a watch-and-wait
      approach is appropriate. Hydroxycarbamide is generally first-line therapy.
      Concerns for possible leukemogenicity make anagrelide or interferon-alpha
      possible choices in younger patients and those who are resistant or intolerant to
      hydroxycarbamide. Each pharmacotherapy is associated with specific long-term
      risks and benefits. The potential risk of major bleeding is the main drawback of
      aspirin. Hydroxycarbamide is an established, effective drug for ET, but it may
      increase the risk of transformation to acute myeloid leukaemia and may give
      mucocutaneous ulcers. Anagrelide is a licensed treatment that also reduces
      platelet counts and is generally well tolerated, with evidence that some common
      side effects diminish over time. Anagrelide can have cardiac effects due to
      inhibition of phosphodiesterase III and therefore requires cautious use in
      patients with cardiac insufficiency. There is no evidence of leukaemogenicity
      with anagrelide or interferon-alpha therapy. Interferon-alpha is the only
      treatment suitable for use during pregnancy, although it is not licensed in ET.
      While it is effective for platelet reduction, the use of interferon-alpha is
      restricted by psychiatric side effects. Our knowledge of the optimum
      pharmacotherapy for each patient with ET continues to evolve through research and
      clinical trials, particularly into the molecular basis of the disease.

PMID- 18629499
TI  - The use of erythropoiesis-stimulating agents in patients with non-myeloid
      hematological malignancies: a systematic review.
AB  - The effectiveness of erythropoiesis-stimulating agents (ESAs) for the treatment
      of anemia in patients with non-myeloid hematological malignancies needs to be
      assessed as the response to their administration is not uniform and their cost is
      high. We conducted a systematic review (SR) of the literature to identify reports
      of the effect of ESAs on survival, quality of life (QOL), transfusion
      requirements, and anemia. The entries to MEDLINE, EMBASE, and the Cochrane
      Library databases, and abstracts published in the proceedings of the annual
      meetings of the American Society of Clinical Oncology and the American Society of
      Hematology were searched. Seventeen reports and five abstracts of randomized
      trials fulfilled prospective criteria for inclusion. Five trials reported on
      survival; three failed to detect differences between groups and two demonstrated
      inferior survival in patients allocated to an ESA. Seven trials and three
      abstracts reported on QOL with four articles and three abstracts describing
      improvements in patients allocated to erythropoietin. However, important
      methodologic limitations were identified in these reports. Seven randomized
      controlled trials reported a reduction in the proportion of patients transfused.
      The absolute risk reduction in transfusions ranged from 15% to 24%. This is the
      only SR that assesses the use of erythropoiesis-stimulating agents specifically
      in patients with hematological malignancies. We conclude that available data
      evaluating ESAs in patients with hematologic malignancies demonstrate that these
      agents reduce transfusion requirements. Limitations of these data preclude
      conclusions that these agents improve QOL. More data are required to confirm the
      inferior survival associated with ESAs.

PMID- 18629500
TI  - MDR1 modulates apoptosis in CD34+ leukemic cells.

PMID- 18629501
TI  - Central venous catheter-related infections in hematology and oncology :
      guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society
      of Hematology and Oncology (DGHO).
AB  - Catheter-related infections (CRI) cause considerable morbidity in hospitalized
      patients. The incidence does not seem to be higher in neutropenic patients than
      in nonneutropenic patients. Gram-positive bacteria (coagulase-negative
      staphylococci, Staphylococcus aureus) are the pathogens most frequently cultured,
      followed by Candida species. Positive blood cultures are the cornerstone in the
      diagnosis of CRIs, while local signs of infection are not necessarily present.
      Blood cultures should be taken from peripheral blood and from the venous
      catheter. A shorter time to positivity of catheter blood cultures as compared
      with peripheral blood cultures supports the diagnosis of a CRI. In many cases, a
      definite diagnosis requires catheter removal and microbiological analysis. The
      role plate method with semiquantitative cultures has been established as standard
      in most laboratories. Antimicrobial treatment of CRI should be directed by the in
      vitro susceptibility of the isolated pathogen. Primary removal of the catheter is
      mandatory in S. aureus and Candida infections, as well as in case of tunnel or
      pocket infections. Future studies will elucidate whether the rate of CRI in
      neutropenic patients may be reduced by catheters impregnated with antimicrobial
      agents.

PMID- 18629502
TI  - Cannabinoid receptor-independent cytotoxic effects of cannabinoids in human
      colorectal carcinoma cells: synergism with 5-fluorouracil.
AB  - Cannabinoids (CBs) have been found to exert antiproliferative effects upon a
      variety of cancer cells, including colorectal carcinoma cells. However, little is
      known about the signalling mechanisms behind the antitumoural effect in these
      cells, whether the effects are shared by endogenous lipids related to
      endocannabinoids, or whether such effects are synergistic with treatment
      paradigms currently used in the clinic. The aim of this preclinical study was to
      investigate the effect of synthetic and endogenous CBs and their related fatty
      acids on the viability of human colorectal carcinoma Caco-2 cells, and to
      determine whether CB effects are synergistic with those seen with the pyrimidine
      antagonist 5-fluorouracil (5-FU). The synthetic CB HU 210, the endogenous CB
      anandamide, the endogenous structural analogue of anandamide, N-arachidonoyl
      glycine (NAGly), as well as the related polyunsaturated fatty acids arachidonic
      acid and eicosapentaenoic acid showed antiproliferative and cytotoxic effects in
      the Caco-2 cells, as measured by using [(3)H]-thymidine incorporation assay, the
      CyQUANT proliferation assay and calcein-AM fluorescence. HU 210 was the most
      potent compound examined, followed by anandamide, whereas NAGly showed equal
      potency and efficacy as the polyunsaturated fatty acids. Furthermore, HU 210 and
      5-FU produced synergistic effects in the Caco-2 cells, but not in the human
      colorectal carcinoma cell lines HCT116 or HT29. The compounds examined produced
      cytotoxic, rather than antiproliferative effects, by a mechanism not involving CB
      receptors, since the CB receptor antagonists AM251 and AM630 did not attenuate
      the effects, nor did pertussis toxin. However, alpha-tocopherol and the nitric
      oxide synthase inhibitor L-NAME attenuated the CB toxicity, suggesting
      involvement of oxidative stress. It is concluded that the CB system may provide
      new targets for the development of drugs to treat colorectal cancer.

PMID- 18629503
TI  - Urodynamic changes and response rates in patients treated with permanent
      electrodes compared to conventional wire electrodes in the peripheral nerve
      evaluation test.
AB  - OBJECTIVES: Sacral neuromodulation having become established as an essentially
      effective new therapeutic modality, both in patients with anticholinergic-therapy
      refractory overactive bladder (OAB) and with chronic urinary retention. It is
      important to establish which patients might profit from this kind of therapy in
      order to ensure, by means of a peripheral nerve evaluation (PNE) test, that the
      implantation of a permanent stimulating device is effective. In a retrospective
      study we compared the urodynamic outcome of two different techniques
      (implantation of the permanent neurostimulation electrodes so-called "two-stage
      implantation" vs. conventional PNE). METHODS: We performed a sacral nerve
      stimulation in 53 patients (30 urinary retention, 23 OAB syndrome). In 42
      patients, we performed a conventional PNE, 11 patients received "two-stage
      implantation" with implantation of the permanent electrodes. RESULTS: In 20 cases
      the conventional PNE-test (cPNE) was successful (47.6% of all cPNE). The response
      rate of "two-stage-implantation" (permanent electrodes) was 81.8%. In patients
      with overactive bladder the bladder capacity was increased by 30% with cPNE (P =
      0.068) versus 52% when permanent electrodes were used (P = 0.017). Bladder
      instabilities were reduced by ca. 75%. In urinary retention, the cPNE versus
      permanent electrodes led to an increase of the maximum detrusor pressure by 68
      versus 94% with reduction of residual urine by 71% (P = 0.068) versus 66% (P =
      0.042). CONCLUSIONS: The results of this study show that application of permanent
      quadripolar electrodes during PNE prior to chronic neuromodulator implantation
      leads to significantly higher responder rates and enables more efficient patient
      selection.

PMID- 18629504
TI  - Retroperitoneal laparoscopic radical nephrectomy: intermediate oncological
      results.
AB  - OBJECTIVES: To report the intermediate oncological results of laparoscopic
      radical nephrectomy by retroperitoneal approach. METHODS: From 1995 to 2006, 146
      consecutive patients with removal of a malignant kidney tumor by laparoscopic
      retroperitoneal radical nephrectomy were analysed retrospectively. The patients
      were followed clinically, biologically and radiologically every 6 months. Disease
      free survival and specific survival were determined among patients free of
      metastasis at surgery. RESULTS: Patient's average age was 61.1 years (25-85). The
      pathology of these cancers were: 108 clear cell carcinomas, 26 papillary
      carcinomas, 10 chromophobe carcinomas, and 2 miscellaneous. The T stage were: 105
      pT1, 12 pT2, and 29 pT3 (TNM 2002). The Fuhrman grade were: I in 23 cases, II in
      70 cases, III in 40 cases, and IV in 9 cases. The surgical margins were positive
      in 2. No port site recurrence occurred. The average follow-up was 35.4 months (1
      137). Five patients had metastatic disease at presentation. Tumor progression was
      observed among 19 patients, in the form of a local (1) or remote recurrence (18).
      Fourteen patients died, including 7 because of their tumor. The disease-free
      survival at 5 and 10 years, were respectively 87.3 and 73.2%, and the cancer
      specific survival were 96.2 and 92.0%, respectively. CONCLUSIONS: The
      laparoscopic retroperitoneal radical nephrectomy offers intermediate oncological
      results compatible with appropriate carcinological efficacy.

PMID- 18629505
TI  - Evaluation of complications in endoscopic extraperitoneal radical prostatectomy
      in a modular training programme: a multicentre experience.
AB  - OBJECTIVES: Structured mentor-based "modular surgical training (MST)" has proved
      to be an effective way to teach endoscopic extraperitoneal radical prostatectomy
      (EERPE) safely to residents, even those without previous experience in
      laparoscopic surgery. We report on complications in early patient series from two
      centres where EERPE was established by MST held at the same teaching centre.
      METHODS: Three trainees from two departments underwent MST at the same teaching
      centre. Thereafter, they were supervised by their mentor at their hospital. Peri
      operative and post-operative complications of the first 245 (centre 1) and 288
      (centre 2) cases were analysed retrospectively by the revised Clavien
      classification and compared to a large series (n = 1300) from the teaching
      centre. P < 0.05 were considered significant. RESULTS: In total, 427 (80.1%)
      patients were without complications at the training centres. Intra-operative
      complications occurred in 8 (1.6%) patients. Among 98 (18.3%) patients with post
      operative complications, 41 (7.7%) and 7 (1.3%) patients with Clavien grade I and
      II complications required no or pharmacological treatment, respectively. Totally,
      40 (7.5%) patients required surgical intervention (Clavien grade III). Grade IV
      and V complications were observed in 9 (1.7%) and 1 (0.2%) cases, respectively. A
      comparison of complications from the training centres and the teaching centre
      revealed no statistically significant difference. CONCLUSIONS: Novice
      laparoscopic surgeons can safely learn EERPE by a structured, mentor based,
      modular surgical training programme without putting patients at risk. The
      complication rates in early patient series are low and comparable to those of the
      teaching centre.

PMID- 18629506
TI  - [Quality of life - methodology and clinical practice aspects with a focus on
      ocular medicine].
AB  - Due to the demographic development in western industrialised countries, the
      proportion of visually impaired persons is likely to increase in the future.
      Currently there is a shift in scientific recognition from relative neglect of
      psychopathological distress in the visually impaired to better notice of disease
      related subjective impairments that are detectable with specific questionnaire
      measures. Visual acuity primarily determines the subjective rating of visual
      functioning independent from the eye disease. Ophthalmic patients who show only
      mild symptoms from a medical point of view normally suffer considerably
      diminished vision-related quality of life with respect to physical, functional,
      mental, and social aspects. Treatment effects have been shown using vision
      related quality-of-life measures for different ophthalmic diseases, particularly
      cataract surgery. Assessment of vision-related quality of life provides a
      meaningful complement to objective data.

PMID- 18629507
TI  - [Patient reported outcomes. Relevance and application in ophthalmology].
AB  - The use of patient-reported outcomes (PROs) - standardized assessments by the
      patient of the impact of illness or therapy - has been met with increasing
      interest over the last years. Evidence generated from PROs is used not only to
      support claims in the drug regulatory process but is also used in political
      decision making and activities by the pharmaceutical industry. PROs can reflect
      the benefits of a treatment very well because the patient's quality of life is a
      central variable, and its preservation or improvement is certainly the main
      objective of any therapeutic intervention. The routine use of PROs is still
      hampered by several methodological problems. However, there are a number of
      advantages, such as improved interaction between physicians and patients and
      shared decision making, that may result in increased compliance.

PMID- 18629508
TI  - [Quality of life by limited vision in old age: the example of age-related macula
      degeneration].
AB  - Age-related macula degeneration (AMD) is accompanied by considerable consequences
      regarding the psychosocial quality of life. A considerable body of research
      literature now indicates, for instance, an increased rate of depression and
      substantial loss of everyday capabilities in AMD patients. However, inter
      individual differences are large and part of the explanation lies in differences
      in the ability to cope with and detach oneself from aims in life. The negative
      impact of AMD on the qualify of life is associated with a need for psychosocial
      support, but this need is barely met at present. A series of studies nevertheless
      supports the view that successful intervention is possible even with very old
      patients. In this respect the problems at present have less to do with
      recognition than with application and implementation.

PMID- 18629511
TI  - Intestinal schistosomiasis in a traveller returning from Rwanda and Burundi.

PMID- 18629509
TI  - Congenital subependymal giant cell astrocytoma: clinical considerations and
      expression of radial glial cell markers in giant cells.
AB  - OBJECTS: Congenital Subependymal giant cell astrocytoma (SEGA), diagnosed in
      fetal and neonatal period, is extremely rare. Previous studies have reported poor
      surgical outcomes of this small group of patients. We encountered a patient
      diagnosed as congenital SEGA and report the surgical outcome along with
      interesting immuno-phenotypes of giant tumor cells. CASE: Ventriculomegaly and a
      hypoechoic mass near the foramen of Monro were detected in a fetus on prenatal
      ultrasonography in the 35th week of gestation. Surgery was scheduled 2 months
      later to reduce the risk of operative complications. At postnatal 2 months, gross
      total resection of the tumor was achieved without complications. The patient had
      been followed up for 1 year without tumor recurrence. In double
      immunofluorescence, the prototype cells of SEGA expressed a variety of neural
      stem cell (nestin and Sox2) and radial glial cell markers (vimentin and brain
      lipid-binding protein), in addition to glutamate/aspartate transporter and glial
      fibrillary acidic protein. CONCLUSIONS: Congenital SEGA can be successfully
      treated with judicious use of observation period and careful evaluation of
      general conditions. Pathological findings support the concept that SEGA may
      originate from aberrant radial glial cells in the developing brain.

PMID- 18629510
TI  - Cerebellar pilocytic astrocytoma presenting with intratumor bleeding,
      subarachnoid hemorrhage, and subdural hematoma.
AB  - INTRODUCTION: Massive intracranial hemorrhage is a very rare initial presentation
      of cerebellar pilocytic astrocytomas. There are no reports in the medical
      literature on a cerebellar pilocytic astrocytoma presenting with intratumor
      bleeding (ITB), subarachnoid hemorrhage (SAH), and subdural hematoma (SDH). CASE
      REPORT: A 15-month-old boy presented with lethargy and nausea to our hospital.
      Magnetic resonance imaging showed a mass with ITB at the left cerebellar
      hemisphere in addition to SDH in the posterior fossa and SAH at the
      interpeduncular cistern. The patient underwent emergency surgery. On incising the
      dura, we found SDH, the tumor was visible at the cerebellar cortex, and near
      total removal followed. Microscopic examination of tissue sections revealed a
      pilocytic astrocytoma. DISCUSSION: The authors' case is the first report with a
      presentation including ITB, SAH, and SDH. The presumed mechanism of the SAH and
      SDH was leaking of the ITB into subarachnoid and subdural spaces.

PMID- 18629512
TI  - A comparative analysis of two tissue procurement approaches for the genomic
      profiling of clinical colorectal cancer samples.
AB  - BACKGROUND: The basis for personalized medicine is the creation of a repository
      of knowledge about the genetic alterations involved in disease processes.
      Integral to achieving this goal is the querying of well-preserved, high-quality
      human tissue samples. Making these findings relevant involves the interrogation
      of large numbers of samples. The pace with which changes have occurred versus the
      potential pace with which changes can occur may be indicative of problems
      associated with traditional approaches on collecting biospecimens. Therefore,
      transforming personalized medicine from concept to reality may require an
      alternative approach in the field of tissue specimen procurement. MATERIALS AND
      METHODS: "Exfoliation and Enrichment" (EE), a recently described rapid and cost
      effective approach for procuring cells, was utilized and assessed relative to a
      more traditional but temporally and economically comparable approach. Material
      from the same tumor sample, one collected by EE but the other frozen, were
      procured, the DNA extracted, and the samples analyzed at the global and gene
      specific level by array comparative genomic hybridization and quantitative
      polymerase chain reaction, respectively. RESULTS: Both approaches resulted in the
      rapid procurement and retrieval of well-preserved cells and nucleic acids. The
      presence of "contaminating" normal cells in the more traditional approach masked
      the significance of genetic gains and losses, findings that were more readily
      apparent from the material derived by the EE method. CONCLUSION: The EE approach
      represents a cost-effective alternative to traditional cell-procurement methods
      that results in the generation of superior genomic data.

PMID- 18629513
TI  - Report of a family segregating mutations in both the APC and MSH2 genes: juvenile
      onset of colorectal cancer in a double heterozygote.
AB  - BACKGROUND AND AIMS: Mutations in DNA mismatch repair genes are associated with
      high risk of digestive malignancies [hereditary non-polyposis colorectal cancer
      (HNPCC); Lynch syndrome]; mutations of APC and MYH are associated with classic
      and attenuated familial adenomatous polyposis (FAP). Although the early onset of
      tumors in both syndromes is characteristic of their genetic origin, pediatric
      malignancies remain rare. Certain reports have found familial colorectal cancer
      (CRC) occurring in very young patients associated with mutations in more than one
      gene. MATERIALS AND METHOD: A family corresponding to the Amsterdam criteria for
      HNPCC, including two cases of colorectal cancer before the age of 25 years, was
      analyzed for mutations in the MSH2 genes by sequencing. Because polyposis was
      observed in a patient who developed CRC at age 16, the APC gene was also
      sequenced. RESULTS: A truncating mutation in the MSH2 gene, c.258_259delTG, was
      carried by patients developing cancer of the colon (two patients), uterus,
      kidney, bladder, and/or small intestine at ages 16, 24, 43, 44, 45, and 57,
      respectively. A patient with CRC at age 16 was found to carry the APC
      c.3183_3187del5 mutation as well as the MSH2 mutation, and it is inferred that
      her father, deceased of CRC at age 24, was also a double heterozygote.
      INTERPRETATION: These results confirm that vigilance is required when
      interpreting molecular results for families with very young patients, as more
      than one gene may contribute to the genetic risk. Cancer screening measures must
      also be adapted to the earlier and more penetrant risk to double heterozygotes.

PMID- 18629514
TI  - The prognostic importance of thymidylate gene polymorphism in colon cancer stage
      II.

PMID- 18629516
TI  - Sunitinib malate as the salvage therapy in advanced rectal carcinoid tumor.

PMID- 18629515
TI  - Continence disorders after anal surgery--a relevant problem?
AB  - SUBJECT: Anal incontinence is a well-known and feared complication following
      surgery involving the anal sphincter, particularly if partial transection of the
      sphincter is part of the surgical procedure. METHODS: The literature was reviewed
      to evaluate the risk of postoperative incontinence following anal dilatation,
      lateral sphincterotomy, surgery for haemorrhoidal disease and anal fistula.
      RESULTS: Various degrees of anal incontinence are reported with frequencies as
      follows: anal dilatation 0-50%, lateral sphincterotomy 0-45%, haemorrhoidal
      surgery 0-28%, lay open technique of anal fistula 0-64% and plastic repair of
      fistula 0-43%. Results vary considerably depending on what definition of
      "incontinence" was applied. The most important risk factors for postoperative
      incontinence are female sex, advanced age, previous anorectal interventions,
      childbirth and type of anal surgery (sphincter division). Sphincter lesions have
      been reported following procedures as minimal as exploration of the anal canal
      via speculum. CONCLUSIONS: Continence disorders after anal surgery are not
      uncommon and the result of the additive effect of various factors. Certain risk
      factors should be considered before choosing the operative procedure. Since
      options for surgical repair of postoperative incontinence disorders are limited,
      careful indications and minimal trauma to the anal sphincter are mandatory in
      anal surgery.

PMID- 18629517
TI  - Preoperative irradiation with 5 x 5 Gy in a murine isolated colon loop model does
      not cause anastomotic weakening after colon resection.
AB  - INTRODUCTION: There are conflicting studies on the influence of fractionated
      preoperative 5 days of 5 Gy irradiation on tissue oxygenation and subsequent
      colonic anastomotic strength. To elucidate the effect of preoperative irradiation
      on anastomotic strength, an isolated colon loop model was developed. METHODS:
      Male Wistar rats (n = 164) were randomly divided into three groups. One group
      remained untreated (control). In the other two groups, a loop of descending colon
      was exteriorized to create a hernia of the abdominal wall. After 4 weeks'
      recovery, this loop was locally irradiated with 5 x 5 Gy of gamma-rays or sham
      irradiated. One week after (sham-) irradiation, an anastomosis was performed in
      all groups. Tissue oxygenation (StO2) was determined with visible light
      spectroscopy. The animals were sacrificed 3 or 7 days after the operation and the
      anastomosis was tested for bursting pressure and breaking strength. RESULTS:
      Irradiated rats showed significantly more weight loss (90% SD 4.3 of initial body
      weight vs. 96% SD 2.8, p < or = 0.05) and enteritis (18% vs. 5%, p = 0.013)
      compared to sham and control animals. StO2 was not influenced by irradiation and
      was not predictive for anastomotic strength. The control group showed
      significantly lower bursting pressure and breaking strength compared to (sham-)
      irradiated animals. CONCLUSION: We developed a new isolated loop model for
      intermittent irradiation of the colon. Preoperative irradiation of the distal
      part of a colon anastomosis was successfully administered with acceptable side
      effects and did not cause reduced tissue oxygenation nor clinical signs of
      anastomotic weakening, nor objective reduction in bursting pressure and breaking
      strength.

PMID- 18629518
TI  - Validation and clinical significance of a new calprotectin rapid test for the
      diagnosis of gastrointestinal diseases.
AB  - AIMS: Objective of this study was to compare the assay characteristics of a new
      fecal calprotectin rapid test with an enzyme-linked immunosorbent assay (ELISA).
      The second aim was to assess the potential of measuring fecal calprotectin as
      screening method for intestinal inflammation and colorectal malignancies.
      PATIENTS AND METHODS: One hundred forty patients with lower gastrointestinal
      symptoms referred to colonoscopy provided fecal samples (56, control group; 18,
      diverticulosis; 29, colorectal adenoma; 8, colorectal carcinoma (CRC); 18, active
      inflammatory bowel disease (IBD); 11, intestinal infections). Feces were analyzed
      by two assay methods. RESULTS: Compared to the control group (median 25.8
      microg/g), calprotectin levels were significantly increased in adenoma (66.3
      microg/g), CRC (164 microg/g), intestinal infections (306 microg/g), and active
      IBD (797 microg/g). An adequate diagnostic accuracy could be found for active IBD
      with a sensitivity, specificity, and an area under the curve (AUC) of 100%, 79%,
      and 0.955 (ELISA) vs. 89%, 80%, and 0.896 (rapid test). Similar results were
      obtained for CRC (100%, 79%, 0.922 vs. 100%, 80%, 0.948) whereas in adenomas a
      low sensitivity, specificity, and AUC of 55%, 79%, and 0.686 vs. 52%, 80%, and
      0.666 were found for fecal calprotectin. CONCLUSIONS: Both fecal calprotectin
      assays are effective in identifying active IBD and CRC but lack analytical
      sensitivity in separating CRC from adenoma as well as adenoma from the control
      group. The new calprotectin rapid test is a convenient method for assessing the
      calprotectin level in an outpatient setting. Henceforth, it provides a
      precondition for the fecal calprotectin method to challenge fecal occult blood
      testing in further evaluations.

PMID- 18629519
TI  - HMGA2 rearrangements are rare in benign lipomatous lesions of the nervous system.

PMID- 18629520
TI  - Pathogenesis of proximal autosomal recessive spinal muscular atrophy.
AB  - Although it is known that deletions or mutations of the SMN1 gene on chromosome 5
      cause decreased levels of the SMN protein in subjects with proximal autosomal
      recessive spinal muscular atrophy (SMA), the exact sequence of pathological
      events leading to selective motoneuron cell death is not fully understood yet. In
      this review, new findings regarding the dual cellular role of the SMN protein
      (translocation of beta-actin to axonal growth cones and snRNP biogenesis/pre-mRNA
      splicing) were integrated with recent data obtained by detailed neuropathological
      examination of SMA and control subjects. A presumptive series of 10 pathogenetic
      events for SMA is proposed as follows: (1) deletions or mutations of the SMN1
      gene, (2) increased SMN mRNA decay and reduction in full-length functional SMN
      protein, (3) impaired motoneuron axono- and dendrogenesis, (4) failure of
      motoneurons to form synapses with corticospinal fibers from upper motoneurons,
      (5) abnormal motoneuron migration towards ventral spinal roots, (6) inappropriate
      persistence of motoneuron apoptosis due to impaired differentiation and
      motoneuron displacement, (7) substantial numbers of motoneurons continuing to
      migrate abnormally ("heterotopic motoneurons") and entering into the ventral
      roots, (8) attracted glial cells following these heterotopic motoneurons, which
      form the glial bundles of ventral roots, (9) impaired axonal transport of actin,
      causing remaining motoneurons to become chromatolytic, and (10) eventual death of
      all apoptotic, heterotopic and chromatolytic neurons, with apoptosis being more
      rapid and predominating in the earlier stages, with death of heterotopic and
      chromatolytic neurons occurring more slowly by necrosis during the later stages
      of SMA. According to this model, the motoneuron axonopathy is more important for
      pathogenesis than the ubiquitous nuclear splicing deficit. It is also supposed
      that individually variable levels of SMN protein, together with influences of
      other phenotype modifier genes and their products, cause the clinical SMA
      spectrum through differential degree of motoneuron functional loss.

PMID- 18629521
TI  - Dystrophic neurites of senile plaques in Alzheimer's disease are deficient in
      cytochrome c oxidase.
AB  - Double-labeling immunofluorescence and confocal microscopy have been used to
      learn about the local relationship between amyloid, mitochondria, and cytochrome
      c oxidase (COX) in dystrophic neurites of senile plaques in the frontal cortex in
      Alzheimer's disease (AD). Dystrophic neurites surrounding amyloid plaques are
      filled with mitochondrial porin-immunoreactive structures. In contrast with
      tangle-bearing and non-tangle-bearing neurons, which express mitochondrial porin
      and COX subunit 4, porin-immunoreactive neurites of senile plaques lack COX
      subunit 4. Parallel western blot studies in mitochondria-enriched fractions of
      the frontal cortex in the same cases disclosed reduced expression levels of COX,
      but not of prohibitin, in AD stages VB/C of Braak. Co-localization of porin and
      lysosomal associated protein 1, as revealed by double-labeling immunofluorescence
      and confocal microscopy, suggests that mitochondria may be engulfed by lysosomes
      in dystrophic neurites. These findings support a local link between amyloid
      deposition, abnormal mitochondria and impaired respiratory chain function
      (resulting from decrease of COX expression) in dystrophic neurites of senile
      plaques in AD.

PMID- 18629522
TI  - The anterior center edge angle in Lequesne's false profile view: interrater
      correlation, dependence on pelvic tilt and correlation to anterior acetabular
      coverage in the sagital plane. A cadaver study.
AB  - INTRODUCTION: Lequesne's vertical-center-anterior margin (VCA) angle measured on
      the false profile view of the pelvis aims at quantifying the anterior acetabular
      coverage of the femoral head. The anterior delimitation of the acetabular roof is
      often defined on the false profile view but there are no data on its interrater
      reliability. Additionally, it is not known how pelvic tilt may influence this
      angle. Finally, the plane in which this angle is measured lies at an angle of 65
      degrees to the sagittal plane and we wondered if this angle would be transposable
      to the anterior acetabular coverage measured in the sagittal plane. METHODS:
      Eight hips from four cadaver pelvises were investigated by means of a total of 72
      false profile views, each taken in defined pelvic inclinations at 5 degrees
      increments ranging from -20 degrees to +20 degrees , and the VCA angle measured
      by three independent raters. A computed tomography (CT) of each hip was performed
      in a neutral pelvic tilt position and a sagittal 2D reconstruction calculated in
      order to measure anterior coverage in the sagittal plane. The interrater
      reliability of the VCA angles was assessed using the intra-class correlation
      coefficient (ICC). The dependence of the VCA angle on pelvic tilt was assessed by
      regression analysis. The Correlation between the VCA angle and anterior coverage
      in the sagittal plane of the CT was analyzed using a simple linear regression
      model. RESULTS: The interrater reliability for measurements of the VCA angle was
      almost perfect (ICC:0.97). Regression analysis showed that each degree of pelvic
      tilt was accompanied by a change of the VCA angle by a value of 0.63 degrees (P <
      0.001). A low correlation between the VCA angle measured in the false profile
      view and the anterior coverage in the sagittal plane was statistically not
      significant (r = 0.667, P = 0.06). CONCLUSIONS: Lequesne's VCA angle has an
      excellent interrater reliability and represents a reliable measure of acetabular
      dysplasia for comparisons with published data. Lequesne's VCA angle is influenced
      by pelvic tilt in a linear manner. Performing the false profile view in a
      standing position may reduce the clinical relevance of this dependency on pelvic
      tilt. The correlation of Lequesne's VCA angle to anterior acetabular coverage in
      the sagittal plane is low and therefore unsuitable to be transposed into the
      sagittal plane.

PMID- 18629523
TI  - Augmented pin fixation with Cortoss for an unstable AO-A3 type distal radius
      fracture in a patient with a manifest osteoporosis.
AB  - Distal radius fractures are one of the most common fractures in the elderly
      females. In this article, we report a case of a distal radius fracture type AO-A3
      with dorsal instability, in an older woman with manifest osteoporosis, treated
      with minimally invasive Cortoss composite and FFS-wires(R). A 63-year-old woman
      sustained an unstable distal radial fracture of her left wrist after falling from
      a kitchen step. She underwent an open reduction of the fracture and fixation with
      two crossed-fixation pins and Cortoss composite. Post-operative plaster cast
      immobilization was given for 2 weeks, after which the plaster cast and the
      fixation pins were removed. At 4 weeks follow-up, she had a good functional
      result of her left wrist, after 11 months there was a complete return of grip
      strength with also, except for the palmar flexion, a full return of function. We
      report here the first case of a successful surgical treatment with Cortoss
      composite of an AO-A3 type distal radius fracture.

PMID- 18629524
TI  - Frequency rhythmic electrical modulation system in the treatment of chronic
      painful leg ulcers.
AB  - Electrical current has been recommended for use on chronic wounds; however, the
      ability of this modality to improve healing of various types of chronic ulcers,
      arterial, venous, mixed arterial and venous ulcers, diabetic, and pressure ulcers
      is not well established. The purpose of this study was to examine the effect of
      frequency rhytmic electrical modulation system (FREMS) on healing of chronic
      painful leg ulcers.Thirty-five patients with 43 chronic painful leg ulcers
      participated in the study. The subjects were separated into two random groups,
      one treated with FREMS and the control group. Our investigation focused on the
      control of the parameter changes important for ulcer healing: wound surface area,
      wound appearance (fibrin accumulations, exudation, granulation, and
      epithelization), ulcer surroundings and associated symptoms. All the parameters
      were monitored clinically at the beginning, after first, second, and third week,
      and at the end, after 1 and 2 months of administered therapy, when the scores
      were determined. Pain intensity was evaluated with visual analog scale (VAS).
      FREMS therapy was administrated through the device model Aptiva Ballet into
      sessions and several stages. Comparing the findings of decrease leg ulcer
      surface, pain, leg ulcer score, score of vicinity (statistically significant at
      the level P < 0.05) with the controls, it was established that FREMS system
      accelerated ulcer healing, reduced pain and demonstrated better effects compared
      to the control group. The results of the study indicate that FREMS therapy
      accelerates wound closure and depresses the pain of chronic leg ulcers.

PMID- 18629525
TI  - Effects of acitretin on proliferative inhibition and RANTES production of HaCaT
      cells.
AB  - Acitretin is one of the first line drugs to treat psoriasis, though the
      mechanisms are not fully clear. It has been reported that psoriatic keratinocytes
      secreted high level of RANTES, which can induce chemotaxis and activation of T
      cells, thus may play an important role in the pathogenesis of psoriasis. However,
      the effect of acitretin on RANTES production of human keratinocytes and its
      possible signaling are unclear. We observed a significant inhibition of acitretin
      on proliferation of human keratinocytes cell line (HaCaT cells) by MTT assay. The
      inhibition rate of HaCaT cells growth increased gradually from 13.70 to 67.73%
      with acitretin concentration rising from 0.01 to 50 micromol/L. In addition,
      RANTES expression detected in supernatant of HaCaT cells stimulated with TNF
      alpha and IFN-gamma reduced 25, 18 and 12%, respectively, when cultured with 0.1,
      1 and 5 micromol/L acitretin. Furthermore, 1 micromol/L acitretin significantly
      decreased RANTES mRNA level. Finally, acitretin decreased the expressions of
      signal transducer and activator of transcription 1 (STAT1) and nuclear factor
      kappa B (NFkappaB) in nuclei of HaCaT cells stimulated with TNF-alpha and IFN
      gamma, which were determined by immunocytochemistry and western blot. It suggests
      that acitretin can inhibit proliferation and RANTES production of human epidermal
      keratinocytes, and the latter may be related to the inhibition of nuclear
      translocations of STAT1 and NFkappaB.

PMID- 18629526
TI  - The efficacy of venlafaxine in the treatment of women with stress urinary
      incontinence.
AB  - OBJECTIVE: To examine the efficacy of venlafaxine, which is used as an
      antidepressant, in the treatment of stress urinary incontinence. MATERIALS AND
      METHODS: The study was designed as a placebo-controlled, double-blind and
      randomized clinical study. Patients in Group 1 (n=20) were administered 75 mg
      venlafaxine, those in Group 2 (n=20) were administered placebo for 12 weeks. All
      the cases were evaluated in terms of weekly incontinence episode frequency (IEF),
      change in void interval (VI), the Incontinence Quality of Life (I-QOL) in weeks
      0, 4, 8 and 12. Additionally, PGI-S was assessed at baseline and was followed by
      PGI-I evaluations in weeks 4, 8 and 12. RESULTS: Evaluations in weeks 0, 4, 8 and
      12 did not show any significant difference in IEF, VI, IQOL and PGI-I values of
      placebo group (p>0.05). However, in the patients who were administered
      venlafaxine declines in IEF and PGI-I values as well as the elevations in VI and
      IQOL scores showed significant changes parallel to the increasing follow-up
      period (p<0.05). Nausea was observed in 40% of cases in venlafaxine group, and
      15% of those in placebo group (p<0.05). CONCLUSION: It was seen in our study that
      efficacy of venlafaxine started early and the clinical efficacy associated with
      the use of the drug continued in the following months. Venlafaxine should be
      considered a clinically efficient alternative drug in the treatment of SUI.

PMID- 18629527
TI  - Relationship between Cardiofemoral Index and the plasma concentration of brain
      natriuretic peptide in anemic fetuses associated with Rh alloimmunization.
AB  - BACKGROUND: Fetal anemia is a common result of alloimmunization and is an
      important cause of fetal congestive heart failure resulting in heart dilation.
      Fetuses suspected of having heart failure present a higher Cardiofemoral Index
      and an increase in plasma BNP levels, because the cardiac hormonal system is
      activated by increased heart wall stretch due to increased left ventricular
      volume and pressure overload. METHODS: Our group studied 33 pregnant women (22-31
      weeks' gestation at the first cordocentesis) referred for intrauterine fetal
      transfusion due to severe red blood cells isoimmunization. Up to 6 h prior to
      each cordocentesis, all fetuses were submitted to ultrasonography measurements
      where the Cardiofemoral Index was calculated. Samples of blood from the umbilical
      vein were collected for hemoglobin concentration and blood gas measurements.
      Plasma levels of BNP were determined with the use of plasma that had previously
      been frozen and thawed once. Plasma BNP was measured by radioimmunoassay.
      Pearson's correlation test and regression analysis were used to determine the
      association between the plasma concentration of BNP and the Cardiofemoral Index
      of the anemic fetuses with RH alloimmunization. RESULTS: Anemia was severe in 17
      (50%) fetuses, mild in 9 (26.47%) and in 8 patients (23.53%) the fetuses were not
      anemic; hemoglobin ranged from 3.10 to 15.70 g/dl. The Cardiofemoral Index ranged
      from 0.43 to 0.87 and it was altered (>or=0.59) in 23 fetuses. A significant
      positive correlation was observed between BNP plasma fetal concentration and
      Cardiofemoral Index (Pearson r=0.61, P<0.0001). CONCLUSIONS: These results
      suggest that fetal plasma concentration of BNP may increase in fetuses with heart
      dilation leading to a positive association between Cardiofemoral Index and plasma
      concentration of BNP.

PMID- 18629528
TI  - Laparoscopic excision of rudimentary horn pregnancy in a patient with previous
      caesarean section.
AB  - A rudimentary uterine horn is extremely rare and often difficult to diagnose. The
      frequency of this pathology is approximately 1:100,000. The diagnosis is
      sometimes elusive even at surgery. We present a case report of pregnancy in a
      rudimentary horn in the patient with one caesarean and one normal vaginal
      delivery, and we successfully conduct a removal of the rudimentary horn pregnancy
      laparoscopically.

PMID- 18629529
TI  - Combined spinal-epidural analgesia for labor pain: best timing of epidural
      infusion following spinal dose.
AB  - OBJECTIVES: The combined spinal-epidural analgesia (CSEA) technique for labor
      pain has attained wide spread popularity in obstetric anesthesia. The onset of
      analgesia is rapid and reliable, and maternal satisfaction is very high. However,
      the best timing of an epidural infusion following the spinal dose and its effect
      on the total local anesthetics consumption has not been well determined. METHODS:
      A total of 144 consenting healthy nulliparous parturients whose labor was induced
      and who labored under regional analgesia were enrolled in this study. Following
      induction of the CSEA with intrathecal injection of bupivacaine, 2.5 mg and
      fentanyl, 25 microg, the patients were randomized into one of four groups to
      receive a subsequent continuous epidural infusion [E (3), E (30), E (60) and E
      (90)], depending on the timing of the initiation of epidural infusion of 0.1%
      ropivacaine, 0.0002% fentanyl and 1:500,000 epinephrine at the rate of 10 ml/h.
      In study Groups E (3), E (30), E (60) and E (90), epidural infusion was initiated
      3, 30, 60 and 90 min, respectively following spinal induction dose. Patients
      requesting additional labor analgesia were given an epidural bolus (8 ml) of
      ropivacaine, 0.2%. The number of parturients requesting additional boluses of
      ropivacaine and the total dose of ropivacaine required for labor analgesia were
      registered. RESULTS: The numbers of patients who required additional boluses of
      ropivacaine in Group E (3) and Group E (30) were significantly less than those in
      Group E (60) and Group E (90). The total dose of ropivacaine required for labor
      pain in Group E (3) and Group E (30) was insignificantly smaller than the total
      dose required in Group E (60) and Group E (90). CONCLUSION: Our results suggest
      that the best timing of epidural infusion following spinal dose was within 30 min
      of spinal induction dose.

PMID- 18629530
TI  - Esophageal carcinoma during pregnancy: a case report.
AB  - Association of pregnancy with esophageal cancer is an extremely rare event. The
      symptoms are frequently masked by factors related to normal pregnancy and
      diagnostic approaches are restricted by physical and psychological clinical
      events. Hence, the cancer stage is usually advanced at the time of diagnosis. The
      approach to cancer surgery and chemotherapy must be modified in pregnant patients
      to minimize fetal and maternal risks. We present an extremely rare case of
      carcinoma esophagus during pregnancy.

PMID- 18629531
TI  - Sensorineural hearing loss in patients with chronic otitis media.
AB  - Chronic otitis media is generally associated with some degree of hearing loss,
      which is often the patient's chief complaint. This hearing loss is usually
      conductive, resulting from tympanic membrane rupture and/or changes in the
      ossicular chain due to fixation or erosion caused by the chronic inflammatory
      process. When cholesteatoma or granulation tissue is present in the middle ear
      cleft, the degree of ossicular destruction is even greater. An issue that has
      recently gained attention is additional sensorineural hearing loss due to chronic
      otitis media. While the conductive loss can be minimized through surgery,
      sensorineural hearing loss constitutes a permanent after effect, attenuated only
      through the use of a hearing aid. However, a few groups have reported a decrease
      in sensorineural function in these patients as well. This survey study performed
      at a referral center evaluates the occurrence of sensorineural hearing loss in
      ambulatory patients with this disease. We reviewed the files of patients with
      unilateral chronic otitis media. One hundred and fifty patients met the inclusion
      criteria: normal otoscopy and normal hearing in the contralateral ear. MAIN
      OUTCOME MEASURE: bone-conduction threshold averages were calculated for
      frequencies of 500, 1,000, 2,000, 3,000 and 4,000 Hz, with comparison between the
      normal ear and the ear with chronic otitis media. Thresholds were examined
      separately for each frequency. The bone-conduction threshold averages for the
      normal side were lower than those for the ear with chronic otitis media. The
      threshold shift was statistically significant for each frequency (P<0.0001,
      Student's t test). There were differences between the groups when analyzed for
      age (500 and 1,000 Hz) or the presence of cholesteatoma (1,000 Hz). This study
      shows that chronic otitis media is associated with a decrease in cochlear
      function.

PMID- 18629532
TI  - Allele frequency distribution of 13 X-chromosomal STR loci in Pakistani
      population.
AB  - Short tandem repeat (STR) markers are extensively being used for human
      identification as well as paternity and forensic case work. X-chromosome STR (X
      STR) markers are a powerful complementary system especially in deficiency
      paternity testing. Many X-linked microsatellites have been evaluated but further
      studies are required to determine population specific statistics. Here, we report
      allele frequencies of 13 X-linked microsatellites (DXS8378, DXS9902, DXS6810,
      DXS7132, DXS981, DXS6793, DXS6801, DXS6789, GATA172D05, HPRTB, GATA31E08,
      DXS8377, and DXS7423) in the Pakistani population. Blood samples were collected
      from individuals representing all major ethnic groups of the Pakistan population.
      A total of 5-18 alleles were observed for each locus and altogether 109 alleles
      for all 13 X-STR loci. Heterozygosity in females ranged from 0.524 to 0.884. No
      significant deviation was observed from Hardy-Weinberg equilibrium for all 13
      microsatellites. In addition, there was no evidence of linkage disequilibrium in
      any pairs of these markers. These results strongly suggest that the X-linked
      microsatellites described here can potentially serve as an extension to autosomal
      systems currently used in parentage analysis and forensic case work.

PMID- 18629533
TI  - Interindividual variability of electromyographic patterns and pedal force
      profiles in trained cyclists.
AB  - The aim of this study was to determine whether high inter-individual variability
      of the electromyographic (EMG) patterns during pedaling is accompanied by
      variability in the pedal force application patterns. Eleven male experienced
      cyclists were tested at two submaximal power outputs (150 and 250 W). Pedal force
      components (effective and total forces) and index of mechanical effectiveness
      were measured continuously using instrumented pedals and were synchronized with
      surface electromyography signals measured in ten lower limb muscles. The
      intersubject variability of EMG and mechanical patterns was assessed using
      standard deviation, mean deviation, variance ratio and coefficient of cross
      correlation (_R(0), with lag time = 0). The results demonstrated a high
      intersubject variability of EMG patterns at both exercise intensities for
      biarticular muscles as a whole (and especially for Gastrocnemius lateralis and
      Rectus femoris) and for one monoarticular muscle (Tibialis anterior). However,
      this heterogeneity of EMG patterns is not accompanied by a so high intersubject
      variability in pedal force application patterns. A very low variability in the
      three mechanical profiles (effective force, total force and index of mechanical
      effectiveness) was obtained in the propulsive downstroke phase, although a
      greater variability in these mechanical patterns was found during upstroke and
      around the top dead center, and at 250 W when compared to 150 W. Overall, these
      results provide additional evidence for redundancy in the neuromuscular system.

PMID- 18629535
TI  - Prolonged anemia by superinfection of parvovirus B19 in a boy with
      enterohemorrhagic Escherichia coli O157-associated hemolytic uremic syndrome.
AB  - We report a 3-year-old boy with enterohemorrhagic Escherichia coli (EHEC) O157
      associated hemolytic uremic syndrome (HUS). His anemia was associated with
      decreased reticulocyte count and persisted after the recovery from HUS.
      Superinfection of parvovirus B19 (PVB19) was proven by a transient febrile
      episode associated with IgM antibodies to the virus and the delayed appearance of
      IgG antibodies and typical rashes. We conclude that PVB19 infection could induce
      severe persistent anemia in EHEC-associated HUS. Reticulocytopenia is a clue to
      the diagnosis in such cases.

PMID- 18629534
TI  - Effect of cytosolic Mg2+ on mitochondrial Ca2+ signaling.
AB  - Cytosolic Ca2+ signals are followed by mitochondrial Ca2+ uptake, which, in turn,
      modifies several biological processes. Mg2+ is known to inhibit Ca2+ uptake by
      isolated mitochondria, but its significance in intact cells has not been
      elucidated. In HEK293T cells, activation of purinergic receptors with
      extracellular ATP caused cytosolic Ca2+ signals associated with parallel changes
      in cytosolic [Mg2+]. Neither signals were affected by omitting bivalent cations
      from the extracellular medium. The effect of store-operated Ca2+ influx on
      cytosolic Mg2+ concentration ([Mg2+]c) was negligible. Uncaged Ca2+ displaced
      Mg2+ from cytosolic binding sites, but for an equivalent Ca2+ signal, the change
      in [Mg2+] was significantly smaller than that measured after adding extracellular
      ATP. Inositol 1,4,5-trisphosphate mobilized Ca2+ and Mg2+ from internal stores in
      permeabilized cells. The increase of [Mg2+] in the range that occurred in ATP
      stimulated cells inhibited mitochondrial Ca2+ uptake in permeabilized cells
      without affecting mitochondrial Ca2+ efflux. Therefore, the Mg2+ signal generated
      by Ca2+ mobilizing agonists may attenuate mitochondrial Ca2+ uptake.

PMID- 18629536
TI  - Loss of WWOX expression in human extrahepatic cholangiocarcinoma.
AB  - OBJECTIVES: WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene
      that maps to the common fragile site FRA16D on chromosome 16q23.3-24.1. To
      investigate the role of the WWOX gene in the development of extrahepatic
      cholangiocarcinoma (ECC), 30 tissue samples of ECC were examined. METHODS: Loss
      of heterozygosity (LOH), real time reverse transcription PCR (RT-PCR), and
      immunohistochemistry were used to assess the role of WWOX in cholangiocarcinoma.
      RESULTS: LOH was observed in 50% of cases, loss of mRNA was observed in 46.67% of
      the cases and loss of WWOX protein expression was found in 56.67% of ECC tissue
      samples. LOH, mRNA, and protein expression had a significant correlation with
      histological grading. The correlation coefficients were -0.623, -0.475 and 
      0.543, respectively. However, WWOX expression had no correlations with other
      clinicopathological factors such as age, gender, clinical staging or the status
      of preoperative hepatic function (p > 0.05). Poorly differentiated ECC had
      significantly lower expression of WWOX than that of moderately or well
      differentiated ones (p < 0.05). CONCLUSIONS: Loss of WWOX may be involved in the
      tumorigenesis of extrahepati cholangiocarcinoma.

PMID- 18629537
TI  - Prevalence and pathology of camel filariasis in Iran.
AB  - A total of 1,070 camels of different ages and of both sexes slaughtered at
      Mashhad slaughterhouse were inspected for infection with Dipetalonema evansi.
      Microfilariae were found in peripheral blood smears of 221 (20.7%) camels (14%
      females and 23% males). In a second study, the testicles, epididymises, spermatic
      cords, and lungs of 197 male camels were examined, and 165 (83.7%) were infected
      with adult forms of D. evansi. Tissue sections from 30 infected and ten
      uninfected camels were collected and processed routinely for further
      histopathological studies. The arteries infected with D. evansi in the region of
      nodules in testis showed chronic reaction characterized by proliferative and
      hyperplastic changes of the endothelial and fibrous connective tissue layers,
      narrowing the lumen or occluding it. The testicles were either hypertrophic or
      atrophic and showed chronic orchitis with infiltration of lymphocytes,
      eosinophils, macrophages and fibroblasts, parenchymal degeneration, and necrosis
      and, in some cases, with hematoma and hydrocele formation. Necrosis of the
      alveolar walls, atelectasis, pulmonary edema, and fibrosis of the pulmonary
      parenchyma with chronic interstitial pneumonia and rarely mineralization of the
      wall of the blood vessels were also seen in some of the infected animals. D.
      evansi is highly endemic and constitutes an important health problem to camels in
      this area, resulting in high morbidity, impaired working capacity, and lowered
      productivity.

PMID- 18629538
TI  - Reduced folate carrier 80A-->G polymorphism, plasma folate, and risk of placental
      abruption.
AB  - Folate deficiency and maternal smoking are strong risk factors for placental
      abruption. We assessed whether the reduced folate carrier [NM_194255.1: c.80A-->G
      (i.e., p.His27Arg)] (RFC-1) polymorphism was associated with placental abruption,
      and evaluated if maternal smoking modified the association between plasma folate
      and abruption. Data were derived from the New Jersey-Placental Abruption Study--a
      multicenter, case-control study of placental abruption (2002-2007). Maternal DNA
      was assayed for the RFC-1 c.80A-->G polymorphism using a PCR-dependent diagnostic
      test. Maternal folate (nmol/l) was assessed from maternal plasma, collected
      immediately following delivery. Due to assay limitations, folate levels at > or
      =60 nmol/l were truncated at 60 nmol/l. Therefore, case-control differences in
      folate were assessed from censored log-normal regression models following
      adjustment for potential confounders. Distribution of the mutant allele (G) of
      the RFC-1 c.80A-->G polymorphism was similar between cases (52.3%; n = 196) and
      controls (50.5%; n = 191), as was the homozygous mutant (G/G) genotype (OR 1.1,
      95% CI 0.6-2.2). In a sub-sample of 136 cases and 140 controls, maternal plasma
      folate levels (mean +/- standard error) corrected for assay detection limits were
      similar between placental abruption cases (63.6 +/- 5.1 nmol/l) and controls
      (58.3 +/- 4.7 nmol/l; P = 0.270), and maternal smoking did not modify this
      relationship (interaction P = 0.169). We did not detect any association between
      the RFC-1 c.80A-->G polymorphism and placental abruption, nor was an association
      between plasma folate and abruption risk evident. These findings may be the
      consequence of high prevalence of prenatal multivitamin and folate
      supplementation in this population (over 80%). It is therefore not surprising
      that folate deficiency may be rare and that the RFC-1 c.80A-->G polymorphism is
      less biologically significant for placental abruption.

PMID- 18629539
TI  - Evolutionary dynamics of the human ABO gene.
AB  - The ABO polymorphism has long been suspected to be under balancing selection. To
      explore this possibility, we analyzed two datasets: (1) a set of 94 23-Kb
      sequences in European- and African-Americans produced by the Seattle SNPs
      project, and (2) a set of 814 2-Kb sequences in O alleles from seven worldwide
      populations. A phylogenetic analysis of the Seattle sequences showed a complex
      pattern in which the action of recombination and gene conversion are evident, and
      in which four main lineages could be individuated. The sequence patterns could be
      linked to the expected blood group phenotype; in particular, the main mutation
      giving rise to the null O allele is likely to have appeared at least three times
      in human evolution, giving rise to allele lineages O02, O01, and O09. However,
      the genealogy changes along the gene and variations of both numbers of branches
      and of their time depth were observed, which could result from a combined action
      of recombination and selection. Several neutrality tests clearly demonstrated
      deviations compatible with balancing selection, peaking at several locations
      along the gene. The time depth of the genealogy was also incompatible with
      neutral evolution, particularly in the region from exons 6 to 7, which codes for
      most of the catalytic domain.

PMID- 18629540
TI  - BMP4 signaling regulates formation of Hertwig's epithelial root sheath during
      tooth root development.
AB  - Although Hertwig's epithelial root sheath (HERS) performs an important function
      in the formation of the tooth root, the developmental mechanisms that control
      HERS growth and differentiation remain to be thoroughly elucidated. Bone
      morphogenetic protein 4 (BMP4), which is secreted by mesenchymal cells, acts on
      the dental epithelium as a regulator of cell differentiation during crown
      formation. In an effort to determine whether BMP4 specifically regulates the
      development of HERS in the dental epithelium, we assessed the localizations of
      BMP4, BMP receptor-IB (BMPR-IB), and BMPR-II during molar root formation in the
      mouse. HERS cells were shown to express BMPR-IB and BMPR-II. BMP4-positive cells
      were detected densely in the dental papillae around HERS, thereby suggesting that
      BMP4 participated in HERS formation. Beads soaked in BMP4, NOGGIN, or phosphate
      buffered saline (PBS) were implanted into the pulp cavity under culture
      conditions, and the length of HERS was evaluated with regard to the proliferating
      cells. After 12 h, both groups exhibited a similar HERS developmental pattern,
      with the length and shape of HERS bearing a close resemblance to one another.
      However, after 48 h, the observed HERS elongation was significantly shorter in
      the BMP4-treated group. In addition, proliferative cell nuclear antigens were
      detectable only in the NOGGIN- and PBS-treated groups. These findings demonstrate
      that mesenchymally expressed BMP4 regulates HERS development by preventing
      elongation and maintaining cell proliferation. BMP4 may, therefore, prove useful
      as a root-formation regulatory agent in a variety of tissue-engineering
      applications.

PMID- 18629542
TI  - Habitat requirements of weasels Mustela nivalis constrain their impact on prey
      populations in complex ecosystems of the temperate zone.
AB  - Differences in habitat use by prey and predator may lead to a shift of occupied
      niches and affect dynamics of their populations. The weasel Mustela nivalis
      specializes in hunting rodents, therefore habitat preferences of this predator
      may have important consequences for the population dynamics of its prey. We
      investigated habitat selection by weasels in the Bialowieza Forest in different
      seasons at the landscape and local scales, and evaluated possible consequences
      for the population dynamics of their prey. At the landscape scale, weasels
      preferred open habitats (both dry and wet) and avoided forest. In open areas they
      selected habitats with higher prey abundance, except during the low-density phase
      of the vole cycle, when the distribution of these predators was more uniform.
      Also in winter, the distribution of weasels at the landscape scale was
      proportional to available resources. In summer, within open dry and wet habitats,
      weasels preferred areas characterised by dense vegetation, but avoided poor plant
      cover. In winter, weasels used wet open areas proportionally to availability of
      habitats when hunting, but in contrast to summer, they rested only in habitats
      characterized by a lower water level, which offered better thermal conditions. At
      the local scale, the abundance of voles was a less important factor affecting the
      distribution of these predators. Although we were not able to provide direct
      evidence for the existence of refuges for voles, our results show that they may
      be located within habitat patches, where availability of dense plant cover and
      physiological constraints limit the activity of weasels. Our results indicate
      that in complex ecosystems of the temperate zone, characterized by a mosaic
      pattern of vegetation types and habitat specific dynamics of rodents, impact of
      weasels on prey populations might be limited.

PMID- 18629541
TI  - The role of GDNF family ligand signalling in the differentiation of sympathetic
      and dorsal root ganglion neurons.
AB  - The diversity of neurons in sympathetic ganglia and dorsal root ganglia (DRG)
      provides intriguing systems for the analysis of neuronal differentiation. Cell
      surface receptors for the GDNF family ligands (GFLs) glial cell-line-derived
      neurotrophic factor (GDNF), neurturin and artemin, are expressed in
      subpopulations of these neurons prompting the question regarding their
      involvement in neuronal subtype specification. Mutational analysis in mice has
      demonstrated the requirement for GFL signalling during embryonic development of
      cholinergic sympathetic neurons as shown by the loss of expression from the
      cholinergic gene locus in ganglia from mice deficient for ret, the signal
      transducing subunit of the GFL receptor complex. Analysis in mutant animals and
      transgenic mice overexpressing GFLs demonstrates an effect on sensitivity to
      thermal and mechanical stimuli in DRG neurons correlating at least partially with
      the altered expression of transient receptor potential ion channels and acid
      sensitive cation channels. Persistence of targeted cells in mutant ganglia
      suggests that the alterations are caused by differentiation effects and not by
      cell loss. Because of the massive effect of GFLs on neurite outgrowth, it remains
      to be determined whether GFL signalling acts directly on neuronal specification
      or indirectly via altered target innervation and access to other growth factors.
      The data show that GFL signalling is required for the specification of
      subpopulations of sensory and autonomic neurons. In order to comprehend this
      process fully, the role of individual GFLs, the transduction of the GFL signals,
      and the interplay of GFL signalling with other regulatory pathways need to be
      deciphered.

PMID- 18629543
TI  - Nitrogen enrichment modifies plant community structure via changes to plant-soil
      feedback.
AB  - We tested the hypothesis that N enrichment modifies plant-soil feedback
      relationships, resulting in changes to plant community composition. This was done
      in a two-phase glasshouse experiment. In the first phase, we grew eight annual
      plant species in monoculture at two levels of N addition. Plants were harvested
      at senescence and the effect of each species on a range of soil properties was
      measured. In the second phase, the eight plant species were grown in multi
      species mixtures in the eight soils conditioned by the species in the first
      phase, at both levels of N addition. At senescence, species performance was
      measured as aboveground biomass. We found that in the first phase, plant species
      identity strongly influenced several soil properties, including microbial and
      protist biomass, soil moisture content and the availability of several soil
      nutrients. Species effects on the soil were mostly independent of N addition and
      several were strongly correlated with plant biomass. In the second phase, both
      the performance of individual species and overall community structure were
      influenced by the interacting effects of the species identity of the previous
      soil occupant and the rate of N addition. This indicates that N enrichment
      modified plant-soil feedback. The performance of two species correlated with
      differences in soil N availability that were generated by the species formerly
      occupying the soil. However, negative feedback (poorer performance on the soil of
      conspecifics relative to that of heterospecifics) was only observed for one
      species. In conclusion, we provide evidence that N enrichment modifies plant-soil
      feedback relationships and that these modifications may affect plant community
      composition. Field testing and further investigations into which mechanisms
      dominate feedback are required before we fully understand how and when feedback
      processes determine plant community responses to N enrichment.

PMID- 18629544
TI  - Asymmetric competition drives lake use of coexisting salmonids.
AB  - To what degree are population differences in resource use caused by competition
      and the occupation of adjacent positions along environmental gradients evidence
      of competition? Habitat use may be the result of a competitive lottery, or
      restricted by competition. We tested to what extent population differences in
      habitat use of two salmonids, cutthroat trout (Oncorhynchus clarki) and Dolly
      Varden charr (Salvelinus malma) were influenced by interspecific competition. We
      hypothesized that the depth distribution of Dolly Varden charr would be affected
      by competition from the more littoral and surface-oriented cutthroat trout, and
      that the depth distribution of cutthroat trout would be little affected by
      competition from Dolly Varden charr. Sympatric populations of cutthroat trout and
      Dolly Varden charr were created by reciprocal transfers of previously allopatric
      populations in two experimental lakes. We found evidence of asymmetric
      competition, as Dolly Varden charr were displaced from littoral habitats when
      sympatric with cutthroat trout, whereas cutthroat trout remained unaffected by
      the presence of Dolly Varden charr. Evolved differences between the species, and
      differences between experimental lakes, also contributed to population
      differences in habitat use, but asymmetric competition remained as the main
      driver of different depth distributions in sympatry.

PMID- 18629545
TI  - Pectinase partitioning in polyethylene glycol 1000/Na2SO4 aqueous two-phase
      system: statistical modeling of the experimental results.
AB  - Statistical models concerning partitioning of pectinase in polyethylene glycol
      1000/Na2SO4 aqueous two-phase system were established with response surface
      methodology. Concentrations of polyethylene glycol 1000 and Na2SO4 were selected
      as independent variables to evaluate their impact on parameters of partitioning
      in aqueous two-phase system--the partition coefficient of pectinase, purification
      factor and pectinase yield. An experimental space where over 2.5-fold
      purification was achieved, followed by over 90% yield of pectinase. The
      established models showed good prediction of partitioning parameters.

PMID- 18629546
TI  - [Risk minimization in pain therapy: important target but how can it be reached?].

PMID- 18629547
TI  - [Special pediatric care for dying children. IMPaCCT determines the standards for
      pediatric palliative care in Germany].

PMID- 18629550
TI  - The anti-fibrillogenic activity of tetracyclines on PrP 106-126: a 3D-QSAR study.
AB  - There is evidence that Tetracyclines are potentially useful drugs to treat prion
      disease, the fatal neurodegenerative disease in which cellular prion proteins
      change in conformation to become a disease-specific species (PrP(Sc)). Based on
      an in vitro anti-fibrillogenesis test, and using the peptide PrP106-126 in the
      presence of tetracycline and 14 derivatives, we carried out a three-dimensional
      quantitative structure-activity relationship (3D-QSAR) study to investigate the
      stereoelectronic features required for anti-fibrillogenic activity. A preliminary
      variable reduction technique was used to search for grid points where statistical
      indexes of interaction potential distributions present local maximum (or minimum)
      values. Variable selection genetic algorithms were then used to search for the
      best 3D-QSAR models. A 6-variable model showed the best predictability of the
      anti-fibrillogenic activity that highlighted the best tetracycline substitution
      patterns: hydroxyl group presence in positions 5 and 6, electrodonor substituents
      on the aromatic D-ring, alkylamine substituent at the amidic group in position 2
      and non-epi configuration of the NMe2 group.

PMID- 18629551
TI  - A neural networks study of quinone compounds with trypanocidal activity.
AB  - This work investigates neural network models for predicting the trypanocidal
      activity of 28 quinone compounds. Artificial neural networks (ANN), such as
      multilayer perceptrons (MLP) and Kohonen models, were employed with the aim of
      modeling the nonlinear relationship between quantum and molecular descriptors and
      trypanocidal activity. The calculated descriptors and the principal components
      were used as input to train neural network models to verify the behavior of the
      nets. The best model for both network models (MLP and Kohonen) was obtained with
      four descriptors as input. The descriptors were T5 (torsion angle), QTS1 (sum of
      absolute values of the atomic charges), VOLS2 (volume of the substituent at
      region B) and HOMO-1 (energy of the molecular orbital below HOMO). These
      descriptors provide information on the kind of interaction that occurs between
      the compounds and the biological receptor. Both neural network models used here
      can predict the trypanocidal activity of the quinone compounds with good
      agreement, with low errors in the testing set and a high correctness rate. Thanks
      to the nonlinear model obtained from the neural network models, we can conclude
      that electronic and structural properties are important factors in the
      interaction between quinone compounds that exhibit trypanocidal activity and
      their biological receptors. The final ANN models should be useful in the design
      of novel trypanocidal quinones having improved potency.

PMID- 18629549
TI  - C1-C2 arthrodesis after transoral odontoidectomy and suboccipital craniectomy for
      ventral brain stem compression in Chiari I patients.
AB  - Chiari I malformations are often associated with congenital craniocervical
      anomalies such as platybasia, basilar invagination, and retroflexion of the
      odontoid process. Management of ventral brain stem compression associated with
      Chiari I malformations remains controversial, but several authors report a
      significant rate of failure with suboccipital decompression alone in the presence
      of pronounced ventral brain stem compression (VBSC). Treatment options described
      in the literature for these patients involve anterior, posterior, or combined
      decompressions with or without concurrent arthrodesis. A combined anterior and
      posterior approach provides a definitive circumferential decompression but also
      significantly disrupts the stability of the occipitocervical junction usually
      necessitating occipitocervical fixation. We describe an alternative surgical
      treatment for Chiari I patients with significant ventral brain stem compression
      where a combined anterior and posterior decompression was considered necessary.
      We report two patients who underwent transoral odontoidectomy with preservation
      of the anterior arch of the atlas and suboccipital craniectomy with C1
      laminectomy followed by C1-C2 arthrodesis. Preservation of the anterior arch of
      the atlas in conjunction with C1-C2 arthrodesis stabilizes the occipito-atlanto
      axial segments while conserving more cervical mobility as compared to an
      occipitocervical fusion.

PMID- 18629552
TI  - Piezoosteotomy in orthognathic surgery versus conventional saw and chisel
      osteotomy.
AB  - INTRODUCTION: Piezoosteotomy was assessed as alternative osteotomy method in
      orthognathic surgery regarding handling, time requirement, nerve and vessel
      impairment. MATERIALS AND METHODS: In this comparative clinical experience, 90
      patient's orthognathic surgery procedures were performed in typical distribution
      prospectively by piezoosteotomy: 34 (38%) monosegment, 47 (52%) segmented LeFortI
      osteotomies, 94 (52%) sagittal split osteotomies, 11 (12%) symphyseal, and 4 (2%)
      mandibular body osteotomies. As controls served 90 retrospective patients with
      conventional saw and chisel osteotomy: 58 (64%) monosegment, 27 (30%) segmented
      LeFortI osteotomies, 130 (72%) sagittal split, and 4 (4%) symphyseal osteotomies.
      RESULTS AND DISCUSSION: Piezoosteotomies were individually designed to
      interdigitate the jaw segments after repositioning. The pterygomaxillary suture
      weakened angulated tools; auxiliary chisels were required in 100% of cases for
      the nasal septum and lateral nasal walls, in 33% for pterygoid processes. The
      dorsal maxilla as the pterygoid process were easily reduced; 15% mandibular
      osteotomies required sawing, while the lingual dorsal osteotomy was performed by
      manual feedback due to limited visibility. Bloodloss decreased from average 537
      +/- 208 ml vs. 772 +/- 338 ml (p = 0.0001). Operation time remained unchanged:
      223 +/- 70 min vs. 238 +/- 60 min (p = 0.2) for a conventional bimaxillary
      procedure. Clinical courses and reossification were unobtrusive. Alveolar
      inferior nerve sensitivity was retained in 98% of the piezoosteotomy collective
      versus 84% of controls (p = 0.0001) at 3 months postoperative testing.
      CONCLUSION: Piezoelectric osteotomy did not prolong the operation and reduced
      blood loss as alveolar nerve impairment. A few patients required additional
      sawing or chisel. Piezoelectric screw insertion as complex osteotomies may be
      initiated to simplify the procedure and increase segment interdigitation after
      repositioning as to minimize the osteofixation time and dimensions.

PMID- 18629553
TI  - Soft-tissue changes in association with anterior maxillary osteotomy: a pilot
      study.
AB  - INTRODUCTION: The purpose of this study was to investigate and predict soft
      tissue changes in the forehead, nose, lips, and chin in association with anterior
      maxillary osteotomy. MATERIALS AND METHODS: The sample consisted of 20 adult
      patients (seven men and 13 women, 29.1 years of age immediately before surgery).
      Both hard- and soft-tissue changes were evaluated using a set of lateral
      cephalograms taken immediately before and at 7 months after surgery. Pearson
      correlation coefficients were computed to examine the relationship between hard-
      and soft-tissue changes. A prediction model was developed using a multiple
      regression equation. RESULTS AND DISCUSSION: The findings were as follows: (1)
      Hard-tissue changes were only observed in the maxillary region. Soft-tissue
      changes included backward displacement of the subnasale and the upper and lower
      lips. (2) The highest correlation coefficient was obtained between hard- and soft
      tissue changes in the upper lip region. (3) The horizontal soft-tissue change in
      the upper lip region was predicted using a multiple regression equation. These
      results suggest that anterior maxillary osteotomy influences hard- and soft
      tissue changes in the upper lip region and that the response in the horizontal
      dimension in association with surgery can be predicted.

PMID- 18629554
TI  - Detection of Pseudomonas aeruginosa producing metallo-beta-lactamase VIM-2 in a
      central hospital from Portugal.

PMID- 18629555
TI  - Endocrine dysfunction in leprosy.
AB  - Leprosy is still an endemic disease, especially in Third World countries, and,
      because of migration, it still persists in Europe and the United States. The
      disease affects the peripheral nerves, skin, and multiple internal organs, making
      its clinical recognition difficult. In particular, the endocrine manifestations
      caused by leprosy have been underestimated, even by specialists. The endocrine
      changes present in leprosy include hypogonadism, sterility, and osteoporosis. In
      addition, the spectral immune nature of leprosy offers an attractive model to
      investigate the pathogenetic correlation between the patterns of inflammation in
      the poles of its spectrum and the hormonal disarrangements observed in this
      disease. It is important that those involved in leprosy management be aware of
      the potential endocrine changes and their treatment to address the disease in all
      of its aspects. In this article, we review the findings on endocrine dysfunction
      in leprosy, including a survey of the literature and of our own work.

PMID- 18629556
TI  - Clinical and echocardiographic risk factors for embolism and mortality in
      infective endocarditis.
AB  - Data about predictors of embolism in patients with infective endocarditis (IE)
      are conflicting. This study aimed to investigate clinical and transoesophageal
      echocardiography (TEE) characteristics in predicting embolism and six-month
      mortality. In this observational cohort study, 216 patients with definite left
      sided IE, according to the modified Duke criteria, were prospectively recruited.
      All patients underwent TEE. 'Any embolism' was defined as embolism before or
      after initiation of antimicrobial therapy; 'new embolism' included embolism after
      initiation of antimicrobial therapy. Sixty-two of 216 patients (29%) experienced
      any embolism. New embolism occurred in 12 patients (6%), 7 of which were
      postoperative. Factors significantly associated with any embolism were community
      origin of IE and the etiologic microorganism, in particular staphylococci and
      nonviridans streptococci. Vegetation length >10 mm showed a trend towards
      association with new embolism and a mobile vegetation was predictive for new
      embolism. Six-month mortality was 24% (52/216). In multivariable analysis, age,
      vegetation length >10 mm, Staphylococcus aureus, and the type of treatment
      predicted mortality. Multiple emboli showed a trend towards association with
      death. In conclusion, any embolism occurred in over a fourth of patients. A
      mobile vegetation was significantly associated with new embolism, and vegetation
      length >10 mm tended to be associated with new embolism. Vegetation length >10 mm
      predicted six-month mortality, and multiple emboli showed a trend towards
      association with death.

PMID- 18629557
TI  - Effectiveness of highly active antiretroviral therapy administered by general
      practitioners in rural South Africa.
AB  - The purpose of this study was to assess the one-year efficacy of highly active
      antiretroviral therapy (HAART) administered by general practitioners in a primary
      care community clinic in rural South Africa. We performed an observational cohort
      study of 675 treatment-naive human immunodeficiency virus (HIV)-infected patients
      (including 66 children) who began HAART at least 12 months prior to the data
      analyses. Throughout treatment, the CD4+ T-cell count (percentage of CD4+ T-cells
      in children) and plasma HIV-RNA level were determined and the patient's weight
      was recorded. The primary outcome was mortality. Secondary outcomes were viral
      suppression, immunological response, and weight gain. One year after the start of
      HAART, 100 of the 675 (15%) patients were lost to follow-up and 119 patients
      (18%), including six children, died. Mortality was highest during the first few
      months of treatment. Based on an on-treatment analysis at one year after the
      start of therapy, 83% of adults and 71% of children had a viral load <400
      copies/ml; the viral load was <50 copies/ml in 70% of adults and 61% of children.
      At one year, the mean CD4+ T-cell count in adults had increased by 236/mm(3), and
      the mean body mass index (BMI) had increased by 3.5 kg/m(2). In children, the
      mean CD4% had increased by 17.6. A low Karnofsky score and a low baseline CD4+ T
      cell count were independently associated with death. In addition to these
      factors, a low baseline BMI and gender were predictive of a poor immunological
      outcome. Our study shows that adequately monitored HIV/acquired immunodeficiency
      syndrome (AIDS) care administered by general practitioners and their staff is
      feasible and leads to good results in a rural, primary care center in sub-Saharan
      Africa. In order to achieve even better results, early mortality should be
      reduced and efforts should be made to start HAART earlier.

PMID- 18629558
TI  - Clinical relevance of prevention of respiratory syncytial virus lower respiratory
      tract infection in preterm infants born between 33 and 35 weeks gestational age.
AB  - Premature infants are vulnerable to severe respiratory syncytial virus (RSV)
      lower respiratory tract infection (LRTI) resulting in hospitalisation and the
      potential for longer-term respiratory morbidity. Whilst the severity and
      consequence of RSV LRTI are generally accepted and recognised in infants born
      <or=32 weeks gestational age (GA), there is less acknowledgment of the potential
      consequences in infants born 33-35 weeks GA. However, there is a growing body of
      evidence suggesting that infants born between 33 and 35 weeks GA may be equally
      at risk for RSV LRTI as infants born <32 weeks GA. Interrupted lung development
      and an immature immune system have been linked with an increased susceptibility
      for RSV LRTI, along with other environmental, social, and physiological risk
      factors. Currently, the only effective method of preventing RSV LRTI is
      prophylaxis with palivizumab. Often with limited healthcare resources,
      identifying infants at greatest risk of RSV LRTI who would potentially benefit
      most from prophylaxis is highly desirable, particularly in the 33-35-week GA
      group. The purpose of this article is to examine the causes and consequences of
      RSV LRTI in infants born 33-35 weeks GA, and look at the potential for using risk
      factors to identify high risk infants and, thereby, optimise prophylaxis. The
      causes and consequences of RSV LRTI in infants born 33-35 weeks GAA were
      determined via literature review. A number of underlying risk factors that
      significantly increase the risk of severe RSV LRTI and subsequent hospitalisation
      in this group of infants have been identified, most notably from the FLIP and
      PICNIC studies. A European predictive model based on the risk factors in the FLIP
      study has recently been developed and validated, which will aid identification of
      infants born between 33 and 35 weeks GA with the highest risk of RSV
      hospitalisation. Implementation of this model and prophylaxis of infants born
      between 33 and 35 weeks GA should be a national or regional decision, taken in
      perspective of other public health needs.

PMID- 18629559
TI  - Combined computational study of mechanical behaviour and drug delivery from a
      porous, hydroxyapatite-based bone graft.
AB  - This paper presents a numerical model of a porous, hydroxyapatite-based bone
      graft also suitable as a drug delivery device. The graft was positioned in
      different sites and with different porosities inside a human femur model. The
      structural analyses were carried out to verify the graft mechanical strength,
      using the Tsai-Wu criterion, and the maximum porosity at which static failure
      does not occur. A local stress shielding risk was also calculated as the ratio
      between the bone stress in the intact condition and the stress after implantation
      of the graft. Drug release kinetics was calculated by means of the finite element
      method. High porosity grafts were found to fail in all implantation sites. Lower
      porosity grafts showed to have adequate strength if implanted in some positions,
      while provided insufficient resistance for other implantation sites. Drug release
      kinetics was found to be strongly dependent both on the porosity of the graft and
      the bone density near the bone-graft interface.

PMID- 18629560
TI  - Improving conjugation efficacy of Sorangium cellulosum by the addition of dual
      selection antibiotics.
AB  - The conjugation protocols in myxobacterium Sorangium cellulosum are often
      inapplicable due to the strain-specific sensitivity to the presence of
      Escherichia coli cells or the resistances to many antibiotics. Here we report
      that the conjugative transfer of the mobilizable plasmid pCVD442 from E. coli
      DH5alpha (lambda pir) to Sorangium strains could be greatly increased by the
      presence of low doses of dual selection antibiotics in the mating medium. The
      improvement was efficient in either E. coli-tolerant or sensitive Sorangium
      strains. For those phleomycin and hygromycin tolerant Sorangium strains,
      chloramphenicol-resistance gene was developed as a new selectable marker by
      driving the resistance gene with the aphII promoter. Using the improved protocol,
      the epothilone biosynthetic pathway was inactivated by an insertion mutation in
      the biosynthetic genes of the producing Sorangium strains.

PMID- 18629561
TI  - Dietary conjugated linoleic acid renal benefits and possible toxicity vary with
      isomer, dose and gender in rat polycystic kidney disease.
AB  - Conjugated linoleic acid (CLA) is anti-proliferative and anti-inflammatory in the
      Han:SPRD-cy rat model of kidney disease. We used different doses of CLA and
      examined effects on renal histological benefit, the renal PPARgamma system and
      hepatic and renal levels of CLA isomers. Male and female offspring of Han:SPRD-cy
      heterozygotes were fed diets with 0, 1 or 2% CLA isomer mixture for 12 weeks
      before dual-energy X-ray absorptiometry, harvest of renal and hepatic tissue for
      histologic and lipid analysis. Both CLA diets reduced body fat content in both
      genders but did not change lean body mass. CLA produced a dose dependent
      reduction in female renal cystic change. CLA reduced fibrosis, but this reduction
      was significantly less with higher dose in males. CLA reduced macrophage
      infiltration, tissue oxidized LDL content and proliferation of epithelial cells.
      Serum creatinine rose significantly in female animals fed CLA diets. CLA
      treatment did not change PPARgamma activation. A significant negative correlation
      with renal content of the 18:2 c9,t11 isomer and the sum of histologic effects
      was identified. CLA reduces histologic renal injury in the Han:SPRD-cy rat model
      probably inversely proportionate to c9,t11 renal content. Possible functional CLA
      toxicity at high dose in female animals warrants further exploration.

PMID- 18629562
TI  - Nystatin interferes with the effects of N-methyl-N'-nitro-N-nitrosoguanidine on
      sphingolipid metabolism in human FL cells.
AB  - Previously we have shown that an alkylating agent N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) can induce receptor clustering and the activation of a
      downstream signal molecule NF-kappaB, and that the receptor clustering is
      associated with changes in sphingolipids metabolism. On the other hand, the
      polyene antibiotic nystatin can block MNNG-induced receptor clustering. In this
      study, using a lipidomic approach, we further evaluated whether nystatin
      influenced the effects of MNNG on sphingolipids metabolism. It was found that
      nystatin itself induced changes in the sphingolipids profile in human amnion FL
      cells to a certain extent, including an increase or decrease of some sphingolipid
      species. Interestingly, nystatin can block, at least partially, the changes of
      sphingolipids-induced by MNNG. In addition, nystatin can also partially inhibit
      the activation of NF-kappaB induced by MNNG. Neither MNNG nor nystatin affects
      the mRNA levels of serine palmitoyltransferase, acid sphingomyelinase (ASM), and
      sphingomyelin synthase, key enzymes in the sphingolipids biosynthesis pathway.
      However, MNNG can activate ASM and neutral sphingomyelinase, while nystatin
      preincubation inhibits the activation. Taken together, these data suggested that
      nystatin interferes with the effects of MNNG, and might elicit its function
      through altered sphingolipids metabolism.

PMID- 18629563
TI  - Pay for performance: what the urogynecologist should know.
AB  - As urogynecologists, we should educate ourselves about pay for performance and be
      proactive in the development of outcome measures.

PMID- 18629564
TI  - Bone density and fragility fractures in patients with developmental disabilities.
AB  - We investigated prior fractures, osteoporosis risk factors, and bone mineral
      density (BMD) in 107 institutionalized adults with developmental disabilities. We
      found a very high prevalence of BMD in the osteoporotic range and a significant
      correlation between lower BMD and prior fragility fractures. INTRODUCTION: The
      purpose of this study was to investigate factors contributing to osteoporosis and
      fragility fractures among developmentally disabled adults. METHODS: Adults from a
      residential center participated in a prospective study in which bone mineral
      density (BMD) at the forearm and heel were measured with a portable X-ray
      densitometer. Prior fragility fractures were identified from chart review.
      RESULTS: Among 107 participants, 84 (78.5%) had a measurement within the
      osteoporotic range. The heel was more severely abnormal (mean T-score -3.1 +/-
      1.5) than the forearm (-1.6 +/- 1.3, p < .0.0001). Radiographically confirmed
      prior fragility fractures (17 [16.3%]) were associated with lower heel (p =
      0.0155) and forearm (p = 0.0172) T-scores. In multiple regression analysis, there
      were independent associations between forearm BMD and prior fragility fractures
      (p = 0.0126) and between heel BMD and prior fragility fractures (p = 0.0291). The
      odds ratio for prior fracture increased by 2.02 (95% CI 1.12-3.64) for each
      standard deviation (SD) decrease in heel T-score and by 2.39 (95% CI 1.08-5.32)
      for each SD decrease in forearm T-score. CONCLUSIONS: We found a very high
      prevalence of osteoporotic BMD measurements in institutionalized adults with
      developmental disabilities. Lower heel and forearm BMD measurements were
      significantly and independently associated with prior fragility fractures in this
      population.

PMID- 18629565
TI  - Opportunities in population-specific osteoporosis research and management.

PMID- 18629566
TI  - Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal
      study.
AB  - Peak bone mass is an important determinant of bone mass in later life, but the
      age of peak bone mass is still unclear. We found that bone size and density
      increase and bone turnover decreases until age 25. It may be possible to
      influence bone accrual into the third decade. INTRODUCTION: Peak bone mass is a
      major determinant of bone mass in later life. Bone growth and maturation is site
      specific, and the age of peak bone mass is still unclear. It is important to know
      the age to which bone accrual continues so strategies to maximise bone mass can
      be targeted appropriately. This study aims to ascertain the age of lumbar spine
      peak bone mass. METHODS: We measured lumbar spine BMC, estimated volume and BMAD
      by DXA and biochemical markers of bone turnover in 116 healthy males and females
      ages 11 to 40, followed up at an interval of five to nine years. RESULTS: The
      majority of peak bone mass was attained by the mid-twenties. Increases in BMC in
      adolescents and young adults were mostly due to increases in bone size. Bone
      turnover markers decreased through adolescence and the third decade and the
      decreasing rate of change in bone turnover corresponded with the decreasing rate
      of change in lumbar spine measurements. CONCLUSIONS: Skeletal maturation and bone
      mineral accrual at the lumbar spine continues into the third decade.

PMID- 18629567
TI  - A multifaceted intervention to improve treatment of osteoporosis in
      postmenopausal women with wrist fractures: a cluster randomized trial.
AB  - In a cluster randomized trial, we evaluated the effect of a multifaceted
      intervention (directed at both patient and primary care physician) on the rates
      of testing and treatment of osteoporosis in postmenopausal women within six
      months of their wrist fracture. Compared to usual care, women in the intervention
      practices were three times more likely to receive bone mineral density testing
      and prescribed osteoporosis treatments. INTRODUCTION: Postmenopausal women with
      wrist fractures are at increased risk of future fragility fractures, yet they
      frequently do not receive evaluation and treatment for osteoporosis. We set out
      to evaluate a multifaceted intervention designed to improve management of
      osteoporosis in older women with recent wrist fractures. METHODS: Cluster
      randomized trial of 270 women cared for in 119 primary care practices. We
      recruited postmenopausal women with an acute wrist fracture from the emergency
      departments of hospitals in southeastern Ontario, Canada. Family practices were
      randomly assigned to either the intervention or usual care. The intervention
      consisted of a mailed reminder with a summary of treatment guidelines and letter
      sent to the primary care physician, in addition to an educational package and
      letter to the women. The primary outcome was the proportion of women prescribed
      osteoporosis therapy within 6 months of their fracture. RESULTS: The mean age of
      women was 69(10.9) years. The intervention increased the proportion of women
      started on osteoporosis medications (28% vs. 10%) of controls, adjusted OR 3.45,
      95% CI, 1.58-7.56, p = 0.002) and the proportion who had a bone mineral density
      (BMD) test (53.3% vs. 26%) of controls, OR 3.38, 95% CI, 1.83-6.26, p < 0.001).
      In addition to the intervention, having a female physician was a predictor of
      increased testing and treatment rates. CONCLUSION: A multifaceted intervention
      significantly improved rates of osteoporosis treatment and BMD testing in
      postmenopausal women with wrist fractures.

PMID- 18629568
TI  - Relationship between vitamin D status, body composition and physical exercise of
      adolescent girls in Beijing.
AB  - Little is known about the prevalence of actual vitamin D deficiency in healthy
      school-aged adolescents, particularly in China. The aim of this study was to
      examine the prevalence of hypovitaminosis D and to identify whether there was any
      association between vitamin D status, body composition and physical exercise in
      323 Chinese adolescent girls in Beijing, China (40 degrees N). INTRODUCTION: It
      is well recognized that persistent severe vitamin D deficiency is associated with
      the bone abnormalities of rickets and osteomalacia. However, there is now
      evidence suggesting that low vitamin D status, not previously considered to be a
      state of deficiency is associated with secondary hyperparathyroidism, increased
      bone remodelling and other clinical signs thought only to be found in severe
      vitamin D deficiency. Hypovitaminosis D in healthy children and adolescents has
      been reported frequently in many countries, especially in winter. METHODS: We
      performed a cross-sectional analysis of 323 Chinese adolescent girls in Beijing
      in winter. Mean age of the subjects was 15.0 (+/-0.4) years. About 32.8%, 68.4%
      and 89.2% of the subjects were at risk of vitamin D deficiency when defined as
      plasma concentrations of 25OHD of 25, 37.5 or 50 nmol/L, respectively. RESULTS:
      This cross-sectional analysis of 323 Chinese adolescent girls in Beijing in
      winter showed that hypovitaminosis D was common in these subjects. In addition,
      body mass index, milk intake, participation in organized sports and total
      physical activity were all significant independent determinants of vitamin D
      status. An inverse association was found between plasma 25OHD and intact
      parathyroid hormone (iPTH) concentration. Body mass index (BMI), milk intake,
      participation in organized sports and total physical activity all emerged as
      major independent determinants of vitamin D status as assessed by plasma 25OHD
      concentration. Vitamin D status was positively associated with lean body mass
      (LBM), but there was no association with the degree of body adiposity. Regardless
      of the concentration of 25OHD in blood used to define vitamin D deficiency,
      hypovitaminosis D was common in these subjects. CONCLUSION: It is recommended
      that policies be developed to prevent vitamin D deficiency in adolescent girls.
      Further studies are needed to identify the mechanisms whereby vitamin D status is
      related to exercise and to body composition during growth.

PMID- 18629569
TI  - Effects of a long-term vitamin D and calcium supplementation on falls and
      parameters of muscle function in community-dwelling older individuals.
AB  - In 242 community-dwelling seniors, supplementation with either 1000 mg of calcium
      or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of
      subjects with first falls of 27% at month 12 and 39% at month 20. Additionally,
      parameters of muscle function improved significantly. INTRODUCTION: The efficacy
      of vitamin D and calcium supplementation on risk of falling in the elderly is
      discussed controversially. Randomized controlled trials using falls as primary
      outcome are needed. We investigated long-term effects of calcium and vitamin D on
      falls and parameters of muscle function in community-dwelling elderly women and
      men. METHODS: Our study population consisted of 242 individuals recruited by
      advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum
      25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received
      in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus
      800 IU of vitamin D per day over a treatment period of 12 months, which was
      followed by a treatment-free but still blinded observation period of 8 months.
      Falls were documented using diaries. The study took place in Bad Pyrmont, Germany
      (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees ). RESULTS:
      Compared to calcium mono, supplementation with calcium plus vitamin D resulted in
      a significant decrease in the number of subjects with first falls of 27% at month
      12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76).
      Concerning secondary endpoints, we observed significant improvements in
      quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time
      needed to perform the TUG test of 11%. DISCUSSION: Combined calcium and vitamin D
      supplementation proved superior to calcium alone in reducing the number of falls
      and improving muscle function in community-dwelling older individuals.

PMID- 18629571
TI  - Muscle power is related to tibial bone strength in older women.
AB  - We enrolled 65 to 75 year-old community-dwelling women and measured muscle power,
      strength, physical activity using accelerometry and tibial bone strength using
      peripheral quantitative computed tomography (pQCT). Muscle power contributed 6.6%
      of the variance in the bone strength-strain index and 8.9% in the section modulus
      after accounting for age, height, weight, and physical activity; moderate to
      vigorous physical activity was related to muscle power in the lower extremity.
      INTRODUCTION: Muscle power is associated with DXA measurements of bone mass, but
      it is not known whether muscle power is associated with bone strength. There are
      no reports of investigations that have tested the effect of muscle power on bone
      compartments using advanced imaging. METHODS: We enrolled 74 community-dwelling
      women aged 65-75 years. We measured muscle power and strength of leg extension
      using Keiser air-pressure resistance equipment. All participants wore a waist
      mounted Actigraph accelerometer to record physical activity. We used peripheral
      quantitative computed tomography (pQCT) to measure tibial mid-shaft (50% of the
      site) bone strength (strength-strain index, section modulus). We used Pearson
      correlations and multi-level linear regression to investigate the associations
      between muscle and bone. RESULTS: Muscle power contributed 6.6% (p = 0.007) of
      the variance in the bone strength-strain index and 8.9% (p = 0.001) the variance
      in the section modulus in older women after accounting for age, height, weight,
      and physical activity. Moderate to vigorous physical activity was significantly
      related to muscle power in the lower extremity (r = 0.260; p = 0.041).
      CONCLUSION: Muscle power significantly contributed to the variance in estimated
      bone strength. Whether power training will prove to be a more effective stimulus
      for bone strength than conventional strength training will require further
      studies.

PMID- 18629570
TI  - Biochemical markers of bone turnover: potential use in the investigation and
      management of postmenopausal osteoporosis.
AB  - INTRODUCTION: The aim was to analyse data on the use of biochemical bone turnover
      markers (BTM) in postmenopausal osteoporosis. METHODS: We carried out a
      comparative analysis of the most important papers concerning BTM in
      postmenopausal osteoporosis that have been published recently. RESULTS: The BTM
      levels are influenced by several factors. They are moderately correlated with BMD
      and subsequent bone loss. Increased levels of bone resorption markers are
      associated with a higher risk of fracture. Changes in the BTM during the anti
      osteoporotic treatment (including combination therapy) reflect the mechanisms of
      action of the drugs and help to establish their effective doses. Changes in the
      BTM during the anti-resorptive treatment are correlated with their anti-fracture
      efficacy. CONCLUSION: Biological samples should be obtained in a standardised
      way. BTM cannot be used for prediction of the accelerated bone loss at the level
      of the individual. BTM help to detect postmenopausal women who are at high risk
      of fracture; however, adequate practical guidelines are lacking. BTM measurements
      taken during the anti-resorptive therapy help to identify non-compliers. They may
      improve adherence to the anti-resorptive therapy and the fall in the BTM levels
      that exceeds the predefined threshold improves patients' persistence with the
      treatment. There are no guidelines concerning the use of BTM in monitoring anti
      osteoporotic therapy in postmenopausal women.

PMID- 18629572
TI  - Incidence of fractures compared to cardiovascular disease and breast cancer: the
      Women's Health Initiative Observational Study.
AB  - To compare the absolute risk of fracture to the risk of other conditions by
      race/ethnicity, we studied 83,724 women, aged 70-79. The projected number of
      fractures was similar to or exceeded the combined number of cardiovascular events
      and breast cancers. Osteoporosis prevention efforts should target women of all
      ethnicities. INTRODUCTION: The relative risk of fracture is lower in non-white
      compared to white women but the absolute risk of fracture in comparison to other
      common chronic conditions is uncertain. METHODS: We performed a prospective
      cohort study of 83,724 women, age 50-79 years. Cardiovascular disease (CVD),
      invasive breast cancer and all fractures were identified over an average of 7.7
      +/- 2.6 years. RESULTS: The incidence of fracture, breast cancer, stroke and CVD
      varied across ethnicity. The annualized (%) incidence of fracture was greatest in
      whites (2.4%) and American Indians (2.8%) and lowest among blacks (1.3%). The
      majority of hip fractures occurred in white women. The projected number of women
      who will experience a fracture in one year exceeded the combined number of women
      who would experience invasive breast cancer or a broad category of CVD events in
      all ethnic groups except blacks. In 10,000 black women, an estimated 153 women
      would experience CVD, and 35 women, breast cancer compared to 126 women expected
      to fracture in one year. CONCLUSION: The annual risk of suffering a fracture is
      substantial in women of all ethnicities. Osteoporosis prevention efforts should
      target all women irrespective of their race/ethnic backgrounds.

PMID- 18629574
TI  - Classification and categorisation of psoriatic arthritis.
AB  - For over 30 years, investigators have used the simple but non-validated
      classification criteria suggested by Moll and Wright. Several authors have
      suggested modifications to these but most remain unvalidated or require human
      leukocyte antigen analysis. Now, a worldwide initiative has developed new
      criteria which include both clinical and radiological features. These will
      require further study before they are fully adopted but their improved
      performance should result in less variation between study cohorts. The recurring
      question of disease heterogeneity continues to occupy researchers in this field.
      Despite recent pleas to abandon the original five sub-groups, a case can be made
      for retaining at least the two sub-groups of peripheral and axial disease and,
      possibly, splitting the peripheral disease into oligo- and poly-arthritis.

PMID- 18629573
TI  - Systematic review of trends in prophylaxis of corticosteroid-induced
      osteoporosis: the need for standard audit guidelines.
AB  - Corticosteroid-induced osteoporosis (CIOP) is currently undertreated. Systematic
      review of the literature revealed that the percentage of patients treated
      adequately is dependent on study quality. Therefore, it remains unknown whether
      adherence to the guidelines is really so poor. Five major quality criteria
      provide the standard for future studies on this scope. INTRODUCTION: It has
      recently been stated that the degree of prophylaxis of corticosteroid-induced
      osteoporosis (CIOP) is low and effort should be put into determining reasons for
      non-prescribing of preventive agents. The aim of this study was to identify: how
      many studies adequately audit the prevalent guideline; the longitudinal trends in
      prevention of CIOP; which patient groups appear to be most undertreated; and
      which intervention strategies are effective. METHODS: We performed a
      comprehensive search of MEDLINE and systematically recorded the outcomes and
      quality of published studies, using five major criteria. RESULTS: Twenty-four
      studies were included in the analysis. The quality of the included studies was
      poor (31%) or moderate (37%). There was a longitudinal increase in quality of the
      studies and percentage of prevention. Multivariable linear regression showed that
      the quality of the study was the only independent predictor of the prevention
      rate reported in the study. CONCLUSIONS: The results show undertreatment of CIOP
      might be due to insufficient quality of the studies rather than poor practice or
      failure to recognise the right patients. Future interventions should comply with
      five major quality criteria, and a multifaceted approach is required in order to
      make an impact on the underprescribing of CIOP prophylaxis.

PMID- 18629575
TI  - Cerebral venous thrombosis presenting as a complication of inflammatory bowel
      disease.
AB  - Cerebral venous thrombosis is an uncommon and diverse entity accounting for less
      than 1% of strokes. It can present with a variety of clinical symptoms ranging
      from isolated headaches to deep coma making the clinical diagnosis difficult. We
      present a rare case of cerebral venous thrombosis secondary to dehydration and
      inflammatory bowel disease.

PMID- 18629576
TI  - Intellectual disability, mental illness and offending behaviour: forensic cases
      from early twentieth-century Ireland.
AB  - BACKGROUND: The history of institutional care for individuals with intellectual
      disability is under-researched, complex and troubling. AIMS: To explore the
      experiences of women who may have had intellectual disability and/or mental
      illness and were admitted to forensic psychiatric care in early twentieth-century
      Ireland. METHODS: All female case records at the Central Mental Hospital, Dublin
      from 1910 to 1948 (n = 42) were studied for evidence of possible intellectual
      disability and a series of five cases is presented in detail. RESULTS: These
      committals occurred in the context of adverse social conditions, over-crowding in
      asylums and a belief that rates of mental illness were rising. Particular
      challenges included diagnostic issues (especially in relation to intellectual
      disability), adjustment to asylum environments, mental illness and physical ill
      health. CONCLUSIONS: The institutional experiences of individuals with
      intellectual disability represents an important area for further historical
      research, using larger and more varied forensic populations.

PMID- 18629577
TI  - Feature section, small bowel disease: CT imaging.

PMID- 18629579
TI  - Hemorrhagic cholecystitis as a complication of anticoagulant therapy: role of CT
      in its diagnosis.
AB  - Hemorrhage within the gallbladder lumen is a rare but potentially fatal
      complication of acute cholecystitis. Concomitant anticoagulant therapy increases
      the chances of hemorrhage. In this case report we describe one such case which
      showed active extravasation of the contrast into the lumen of the gallbladder.
      Early diagnosis of this potentially fatal condition is important to facilitate
      urgent surgical treatment.

PMID- 18629580
TI  - Comparison of function of created wetlands of two age classes in central
      Pennsylvania.
AB  - Hydrogeomorphic (HGM) functional assessment models were used to assess whether
      function in created wetlands of two ages (1 year old and >12 years old) was
      equivalent to that of natural (reference) mainstem floodplain wetlands. Reference
      wetlands scored higher than both created age classes for providing energy
      dissipation and short-term surface water storage. Reference wetlands scored
      higher in maintaining native plant community and structure than 1-year-old sites,
      and 12-year-old wetlands scored higher than reference sites for providing
      vertebrate habitat structure. Analysis of individual model variables showed that
      reference wetlands had greater vegetative biomass and higher soil organic matter
      content than both created wetland age classes. Created wetlands were farther from
      natural wetlands and had smaller mean forest patch sizes within a 1-km-radius
      circle around the site than did the reference sites, indicating less hydrologic
      connectivity. Created wetlands also had less microtopographic variation than
      reference wetlands. The 1-year-old created sites were placed in landscape
      settings with greater land use diversity and road density than reference sites.
      The 12-year-old sites had a higher gradient and a higher percentage of their
      surrounding area in urban land use. These results show that the created wetlands
      were significantly structurally different (if not functionally so) from reference
      wetlands even after 12 years. The most profound differences were in hydrology and
      the characteristics of the surrounding landscape. More attention needs to be
      focused on placing created wetlands in appropriate settings to encourage proper
      hydrodynamics, eliminate habitat fragmentation, and minimize the effects of
      stressors to the site.

PMID- 18629581
TI  - Should habitat trading be based on mitigation ratios derived from landscape
      indices? A model-based analysis of compensatory restoration options for the red
      cockaded woodpecker.
AB  - Many species of conservation concern are spatially structured and require
      dispersal to be persistent. For such species, altering the distribution of
      suitable habitats on the landscape can affect population dynamics in ways that
      are difficult to predict from simple models. We argue that for such species,
      individual-based and spatially explicit population models (SEPMs) should be used
      to determine appropriate levels of off-site restoration to compensate for on-site
      loss of ecologic resources. Such approaches are necessary when interactions
      between biologic processes occur at different spatial scales (i.e., local
      [recruitment] and landscape [migration]). The sites of restoration and habitat
      loss may be linked to each other, but, more importantly, they may be linked to
      other resources in the landscape by regional biologic processes, primarily
      migration. The common management approach for determining appropriate levels of
      off-site restoration is to derive mitigation ratios based on best professional
      judgment or pre-existing data. Mitigation ratios assume that the ecologic
      benefits at the site of restoration are independent of the ecologic costs at the
      site of habitat loss. Using an SEPM for endangered red-cockaded woodpeckers, we
      show that the spatial configuration of habitat restoration can simultaneously
      influence both the rate of recruitment within breeding groups and the rate of
      migration among groups, implying that simple mitigation ratios may be inadequate.

PMID- 18629583
TI  - Testicular artery embolization for the treatment of life-threatening hemorrhage
      postorchidectomy.

PMID- 18629582
TI  - Osteopontin expression in squamous cell cancer of the esophagus.
AB  - BACKGROUND: The purpose of this study was to better understand the role of
      osteopontin (OPN) in esophageal squamous cell carcinoma (ESCC) by comparing the
      OPN mRNA level in ESCC tumor tissue and matched normal tissue and by determining
      the prognostic significance of the gene expression. METHODS: Initially, by an
      oligo-nucleotide microarray hybridization technique, OPN expressions were found
      to consistently elevate at least twofold in three ESCC tissues compared with
      their adjacent normal ones. Subsequently, the expression of OPN mRNA was detected
      by real-time QRT-PCR among the 58 fresh surgical ESCC specimens. The clinical
      information was obtained by chart review. RESULTS: OPN mRNA expression was
      detectable in 58 of 58 (100%) tumor specimens and 57 of 58 (98.3%) nonmalignant
      esophageal specimens. OPN expression was higher in tumor tissue than in the
      matched normal tissue in 54 of 58 (93.1%) individual cases. The overall median
      mRNA expression level of OPN was approximately 8.8-fold higher in tumor tissues
      (4.1; range: 0.02-247) compared with matched normal esophageal tissues (0.5;
      range, 0.0-21.4; p < 0.001). Overexpression of OPN mRNA was significantly
      associated with clinical stage (p = 0.01). The more severe the clinical stage
      (from I-II, III, to IV) was the higher frequency of overexpression of OPN mRNA.
      No significant associations were found between overexpression of OPN mRNA and the
      patients' survival (p = 0.27). DISCUSSION: Our findings suggest OPN is associated
      with esophageal tumorigenesis and progression, but not patients' survival.

PMID- 18629584
TI  - Ergonomic assessment of optimum operating table height for hand-assisted
      laparoscopic surgery.
AB  - BACKGROUND: To investigate the influence of the working surface height on task
      performance and muscle workload in hand-assisted laparoscopic surgery. METHODS:
      The standard task used was closure of 5-cm enterotomy inside a hand-assisted
      laparoscopic surgery trainer. Surgeons were instructed to place the sutures 3-5
      mm apart and from the enterotomy edge. Ten surgeons participated in each
      experiment and one task was performed with each level. The first experiment
      compared the quality of task performance and muscle workload with the working
      surface at: elbow level, 10 cm above, 15 cm above and 10 cm below the elbow.
      Further narrower levels (5 cm below, at the elbow and 5 cm above the elbow) were
      investigated in the second experiment. Outcome measures were execution time (s),
      placement error score (mm), leakage pressure (mmHg), number of execution errors,
      muscle workload as measured by integrated electromyography (mV x s) and visual
      analogue score of back discomfort (mm). RESULTS: The first experiment showed that
      15 cm above the elbow level was associated with the longest execution time and
      similar quality of task performance. This level resulted in a higher workload of
      the deltoid of the extracorporeal limb, the arm extensor of the intracorporeal
      side and the trapezius and paraspinal muscles of both intra- and extracorporeal
      limbs. Also, the 10 cm above the elbow level was associated with increased muscle
      workload of the deltoid of extracorporeal limb and the trapezius of both limbs
      compared with the elbow height. The 10 cm below the elbow level was associated
      with increased back discomfort. The second experiment showed that 5 cm below the
      elbow height was associated with increased muscle workload of the arm flexor
      group of the intracorporeal dominant limb. CONCLUSIONS: The optimum table height
      for hand-assisted laparoscopic surgery allows the working surface of the
      extracorporal instrument handle to be at or 5 cm above the elbow level.

PMID- 18629585
TI  - Renal oxidative stress following CO2 pneumoperitoneum-like conditions.
AB  - BACKGROUND: Physiologic renal changes associated with pneumoperitoneum (PNP) have
      been described and various underlying mechanisms have been suggested. We
      investigated the possibility that PNP-associated renal damage is pressure
      dependent, and that oxidative stress is thereby involved. MATERIALS AND METHODS:
      Seventy Wistar rat kidneys (n=10 per group) were isolated. They were perfused
      with oxygenated, warm, Krebs-Henseleit solution containing 5% albumin within an
      isolated environment and subjected to various CO(2) pressures (0 [control], 3, 5,
      8, 12, 15, and 18 mmHg) for 60 min. Half of each group was additionally perfused
      for 30 min at 0 mmHg pressure. RESULTS: Renal flow decreased proportionately to
      the applied pressure as did urine output: both decreased (P < 0.05) after 60 and
      90 min when pressure >or=8 mmHg was applied. Oxygen extraction decreased (P<0.05)
      during PNP in all pressurized groups. Xanthine oxidase (XO) activity and reduced
      glutathione in the tissues increased (P<0.05) proportionately to pressures >or=8
      mmHg. All parameters slightly reversed toward baseline values, upon the release
      of the intra-chamber pressure, except for the 18 mmHg group's values.
      CONCLUSIONS: CO(2)-PNP pressure induces kidney injury, possibly reversible
      immediately after pressure is annulled. Pressure is associated with oxidative
      stress, which interferes with cellular metabolism and function, possibly via an
      ischemic-reperfusion-like mechanism.

PMID- 18629586
TI  - Evaluation of supplemental cautery during endoluminal gastroplication for the
      treatment of gastroesophageal reflux disease.
AB  - BACKGROUND: Endoscopic suture plications at the cardia decreased gastroesophageal
      reflux disease (GERD) symptoms in short-term studies. Pull-through of submucosal
      sutures may lead to loss of efficacy. The application of cautery on mucosal
      surfaces may promote tissue adherence. This study aimed to compare the efficacy
      of endoluminal gastroplication (ELGP) using Endocinch with and without adjuvant
      cautery. METHODS: Vertical plications were created using ELGP. Patients were
      randomized to either ELGP alone or ELGP with an adjuvant bicap cautery. Patients
      were blinded to their randomization category and encouraged to take antisecretory
      medications if needed. Heartburn was scored on a scale of 0 (none), 1
      (occasional), 2 (frequent), or 3 (daily). Patients undergoing a second antireflux
      procedure during the follow-up period were considered study failures and scored
      3. RESULTS: Of the 18 patients enrolled in the study, 1 was lost to follow-up
      evaluation at 12 months and 2 could not be followed up at 24 months. The cautery
      group included 10 patients (9 men) with a mean age of 53.2 years. The group
      without cautery consisted of 8 patients (5 men) with a mean age of 50.4 years.
      The use of ELGP with cautery resulted in a trend toward greater improvement in
      several parameters (heartburn score, total percentage of time that pH was less
      than 4, and medication use) at 12 months than ELGP without cautery. These trends
      were not seen at 24 months, when all but 1 patient had ongoing symptoms, used
      daily proton pump inhibitor/H2-blocker, or went on to undergo a second antireflux
      procedure (2 Nissen and 3 Enteryx). CONCLUSIONS: Cautery numerically improved
      plication persistence, decreased esophageal acid exposure, and improved symptoms
      at 1 year compared with sutures alone. Little or no long-term efficacy of ELGP
      with or without cautery was observed after 2 years of follow-up evaluation.

PMID- 18629587
TI  - Alkaline protease gene cloning from the marine yeast Aureobasidium pullulans HN2
      3 and the protease surface display on Yarrowia lipolytica for bioactive peptide
      production.
AB  - The alkaline protease genes (cDNAALP2 gene and ALP2 gene) were amplified from
      complementary DNA (cDNA) and genomic DNA of the marine yeast Aureobasidium
      pullulans HN2-3, respectively. An open reading frame of 1,248 bp encoding a 415
      amino acid protein with a calculated molecular weight of 42.9 kDa was
      characterized. The ALP2 gene contained two introns, which had 54 and 52 bp,
      respectively. When the cDNAALP2 gene was cloned into the multiple cloning sites
      of the surface display vector pINA1317-YlCWP110 and expressed in cells of
      Yarrowia lipolytica, the cells displaying protease could form a clear zone on the
      double plate containing milk protein and had protease activity. The cells
      displaying alkaline protease were also found to be able to produce bioactive
      peptides from different sources of proteins. The peptides produced from single
      cell protein of marine yeast strain G7a had the highest angiotensin-converting
      enzyme inhibitory activity, while the peptides produced from spirulina protein
      had the highest antioxidant activity. This is the first report that the yeast
      cells displaying alkaline protease were used to produce bioactive peptides.

PMID- 18629588
TI  - Antegrade continence enema in the treatment of congenital fecal incontinence
      beyond childhood.
AB  - PURPOSE: The role of antegrade continence enema for the treatment of congenital
      fecal incontinence in adult patients remains unclear. MATERIALS: Twenty-seven
      patients, median age 19 (range, 17-43) years, with congenital fecal incontinence
      underwent surgery for antegrade continence enema and were prospectively followed
      up for functional outcome after a median of 25 (range, 3-117) months. RESULTS:
      The diagnoses included myelodysplasia (n = 14), anorectal malformations (n = 6),
      and others (n = 7). Antegrade continence enema conduits included appendicostomy
      (n = 22) and cecal (n = 2), ileal (n = 2), and sigmoid (n = 1) tubes. Thirteen
      (48 percent) patients had complications. Eighteen (66 percent) patients became
      fully continent, six (23 percent) had minor, and three (11 percent) major
      soiling. Antegrade continence enema became unnecessary in three patients (11
      percent). Treatment with antegrade continence enema failed in three cases. Of the
      21 patients who continued with antegrade continence enema, 16 (76 percent) are
      fully continent, and bowel function and quality of life was improved in 15 (71
      percent) and 13 (62 percent) patients, respectively. The scores of convenience (1
      = easy, 5 = difficult) and overall satisfaction (1 = poor, 10 = excellent) were
      median 2 (range, 1-4) and 8 (range, 3-10). CONCLUSIONS: Despite numerous
      complications and occasional treatment failures, 90 percent of adult patients
      with congenital fecal incontinence benefited from antegrade continence enema.

PMID- 18629589
TI  - Keystone flap reconstruction of primary melanoma excision defects of the leg-the
      end of the skin graft?
AB  - BACKGROUND: During the last 4 years, the keystone-design fasciocutaneous island
      flap has become the principal form of reconstruction in our unit for primary
      melanoma defects of the leg distal to the knee where primary closure is not
      possible. METHODS: Data describing the primary tumor, surgical management, and
      outcome were collected prospectively for consecutive keystone flap cases. The
      study's primary end points were complication rates and length of hospital stay.
      RESULTS: A total of 176 patients with new primary melanomas of the lower limb
      were treated over 4 years. The average Breslow thickness was 1.33 mm (range, in
      situ to 9.0 mm), and the average width of the defect was 3 cm. The
      reconstructions comprised 106 standard, 65 modified, and 5 double-opposing
      keystone type flaps performed from the knee to the dorsum of the foot.
      Complications that required further therapeutic intervention were seen in eight
      patients (4.6%), with only one partial flap necrosis (.6%) and one total flap
      loss (.6%). In this series, modification of the flap design significantly
      decreased the complication rate (Fisher's exact test, P = .033). There was no
      increase in complications in the distal third of the leg. The procedure was
      performed in day-only surgery setting in almost a quarter of patients.
      CONCLUSION: We present the largest series of flap reconstructions for melanoma of
      the leg. The keystone flap is extremely reliable, affords excellent cosmesis, and
      is technically straightforward to perform. At the Sydney Melanoma Unit,
      reconstruction after primary melanoma excision on the leg has been transformed so
      that skin grafts are now rarely performed.

PMID- 18629590
TI  - The impact of consumer-directed health plans and patient socioeconomic status on
      physician recommendations for colorectal cancer screening.
AB  - BACKGROUND: Consumer-directed health plans are increasingly common, yet little is
      known about their impact on physician decision-making and preventive service use.
      OBJECTIVE: To determine how patients' deductible levels and socioeconomic status
      may affect primary care physicians' recommendations for colorectal cancer
      screening. DESIGN, SETTING, AND PARTICIPANTS: Screening recommendations were
      elicited using hypothetical vignettes from a national sample of 1,500 primary
      care physicians. Physicians were randomized to one of four vignettes describing a
      patient with either low or high socioeconomic status (SES) and either low- or
      high-deductible plan. Bivariate and multivariate analyses were used to examine
      how recommendations varied as a function of SES and deductible. OUTCOME MEASURES:
      Rates of recommendation for home fecal occult blood testing, sigmoidoscopy,
      colonoscopy, and inappropriate screening, defined as no screening or office-based
      fecal occult blood testing. RESULTS: A total of 528 (49%) eligible physicians
      responded. Overall, 7.2% of physicians recommended inappropriate screening; 3.2%
      of patients with high SES in low-deductible plans received inappropriate
      screening recommendations and 11.4% of patients with low SES in high-deductible
      plans for an adjusted odds ratio of 0.22 (0.05-0.89). The odds of a colonoscopy
      recommendation were over ten times higher (AOR 11.46, 5.26-24.94) for patients
      with high SES in low-deductible plans compared to patients with low SES in high
      deductible plans. Funds in medical savings accounts eliminated differences in
      inappropriate screening recommendations. CONCLUSIONS: Patient SES and deductible
      level affect physician recommendations for preventive care. Coverage of
      preventive services and funds in medical savings accounts may help to mitigate
      the impact of high-deductibles and SES on inappropriate recommendations.

PMID- 18629591
TI  - Depression and screening cardiovascular events.

PMID- 18629592
TI  - Early enteral nutrition within 24 h of intestinal surgery versus later
      commencement of feeding: a systematic review and meta-analysis.
AB  - BACKGROUND: We set out to evaluate early commencement of post-operative enteral
      nutrition versus traditional management in patients undergoing gastrointestinal
      surgery. METHODS: Electronic databases were searched, references lists were
      scanned and authors contacted for additional information. We looked for
      randomised controlled trials comparing early commencement of feeding (within 24
      h) with no feeding in patients undergoing gastrointestinal surgery. Primary
      endpoints were wound infections, intra-abdominal abscesses, pneumonia,
      anastomotic leakage, mortality, length of hospital stay and complications of
      feeding. Data were combined to estimate the common relative risk of post
      operative complications and associated 95% confidence intervals. RESULTS:
      Thirteen trials, with a total of 1,173 patients, fulfilled our inclusion
      criteria. Mortality was reduced with early post-operative feeding. Early post
      operative feeding increased vomiting. The direction of effect is suggestive of a
      reduction of risk of post-surgical complications and reduced length of hospital
      stay. CONCLUSION: There is no obvious advantage in keeping patients 'nil by
      mouth' following gastrointestinal surgery. Early enteral nutrition is associated
      with reduced mortality, though the mechanism is not clear. This review supports
      the notion that early commencement of enteral feeding may be of benefit.

PMID- 18629593
TI  - Clonality analysis for multicentric origin and intrahepatic metastasis in
      recurrent and primary hepatocellular carcinoma.
AB  - AIMS: To clarify the incidence of multicentric occurrence (MO) and intrahepatic
      metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus
      in China and to identify the differences between them. METHODS: Histopathologic
      and genetic features of primary and recurrent tumors in 160 cases with HCC were
      analyzed. The two groups, the origin of which was definitely determinable as of
      multicentric occurrence or as of intrahepatic metastasis, were analyzed for their
      disease-free survival and clinicopathological differences. RESULTS: According to
      histopathological findings, 27.5% and 59.4% patients were considered to be MO and
      IM, respectively. By comparing the genetic information of loss of heterozygosity
      and microsatellite instability for 10 different markers between primary and
      recurrent tumor, 30.0% and 63.8% patients with recurrent HCC were considered to
      be MO and IM, respectively. In total, 126 cases with unanimous conclusions from
      the histopathological and genetic method were selected and divided into the MO
      group (37 cases) and the IM group (89 cases). Analysis of stepwise regression
      identified that recurrence time, grading, portal vein invasion, tumor number, and
      Child's stage were the most important discriminating factors between MO and IM (p
      < 0.05). As for their prognosis, Kaplan-Meier and log rank test showed that the
      disease-free survival in the MO group was significantly better than in the IM
      group (p = 0.002). CONCLUSIONS: Combined analysis of histopathological and
      genetic analysis may reflect more exactly the nature of recurrent HCC. The
      incidence of MO in China is lower than in other countries--30% compared to up to
      50% in Japan [Morimoto et al., Journal of Hepatology 39:215-221, 2003; Yamamoto
      et al., Hepatology 29;1446-1452, 1999]. Recurrence time, tumor grading, portal
      vein invasion, tumor number, and Child's stage are the most important
      discriminating factors between MO and IM. The prognosis (disease-free survival)
      of patients with MO compared to IM is significantly better.

PMID- 18629594
TI  - In morbid obesity, metabolic abnormalities and adhesion molecules correlate with
      visceral fat, not with subcutaneous fat: effect of weight loss through surgery.
AB  - BACKGROUND: Decrease of both visceral fat (surgery, physical exercise) and
      subcutaneous fat (liposuction) is accompanied by improvement of insulin
      sensitivity. METHODS: In this study, metabolic variables (glucose, insulin, high
      density lipoprotein-cholesterol, triglycerides, aspartate aminotransferase,
      alanine aminotransferase, uric acid, ferritin) and adhesion molecules (ICAM-1,
      entothelin-1, E-selectin) were determined in 126 morbidly obese subjects before
      and 1 year after bariatric restrictive surgery (laparoscopic gastric banding) and
      correlated with anthropometric measures, i.e., body mass index (BMI) and waist
      circumference (waist), and with echographic measures of thickness of visceral
      (usVT) and subcutaneous (usST) abdominal fat. RESULTS: Under basal conditions and
      after 1 year, metabolic variables correlated with BMI and waist (r from 0.157 to
      0.507, p from 0.0182 to 0.0001) and with usVT (r from 0.211 to 0.512, p from 0.05
      to 0.0001); insulin also correlated with usST, and adhesion molecules only
      correlated with BMI and usVT (r from 0.341 to 0.502, p from 0.0066 to 0.0001).
      Changes of metabolic variables correlated with changes of BMI and waist (r from
      0.163 to 0.356, p from 0.0328 to 0.0001) and with usVT changes (r from 0.211 to
      0.361, p from 0.0339 to 0.0002); changes of adhesion molecules only correlated
      with BMI and usVT changes (r from 0.227 to 0.361, p from 0.0444 to 0.0108).
      Changes of metabolic variables and of adhesion molecules virtually never
      correlated with changes of usST. CONCLUSION: These data indicate that in morbid
      obesity, most metabolic abnormalities are associated with visceral fat and that
      their improvements after weight loss are associated with decrease of visceral
      fat.

PMID- 18629595
TI  - Early postoperative hemorrhage after open and laparoscopic roux-en-y gastric
      bypass.
AB  - BACKGROUND: Early postoperative hemorrhage is an infrequent complication of both
      laparoscopic and open Roux-en-Y gastric bypass (RYGBP). The objective of our
      study is to review the incidence and management of this complication and identify
      contributing clinical and technical risk factors. METHODS: Over a 3-year period,
      1,025 patients underwent RYGBP at our institution. The medical records of
      patients who required postoperative blood transfusions were reviewed for clinical
      presentation, diagnostic evaluation and management. These patients were matched
      for surgical approach (open vs. laparoscopic) in a 1:3 ratio and compared to a
      random group of patients who underwent RYGBP during the same time period.
      RESULTS: Thirty-three patients (3.2%) were diagnosed with postoperative
      hemorrhage, 17 (51.5%) of which were intraluminal. The incidence of hemorrhage
      was higher in the laparoscopic group (5.1% vs. 2.4%, p = 0.02). Comparing
      bleeders to nonbleeders, the average BMI, gender distribution, gastro-jejunostomy
      anastomotic technique (stapled vs. hand sewn) and the postoperative
      administration of ketorolac were not significantly different. The bleeding group
      was older (47.5 vs. 42.8, p = 0.02), had a longer hospital stay (4.9 vs. 3 days,
      p = 0.0001) and was more likely to have received low molecular weight heparin
      (LMWH) preoperatively (p = 0.03). Hemorrhage occurred earlier (13.8 vs. 25.9 h, p
      = 0.039) and was more severe (4.1 vs. 2.3 transfused blood units, p = 0.007) in
      the patients who required surgical reexploration (n = 9). CONCLUSIONS: A
      laparoscopic approach and the preoperative administration of LMWH may increase
      the incidence of early hemorrhage after RYGBP. This complication frequently
      requires surgical reexploration and significantly prolongs the hospital stay.

PMID- 18629596
TI  - Femoral oxygenation during hip resurfacing through the trochanteric flip
      approach.
AB  - Femoral neck fracture is one of the most common complications of hip resurfacing
      and considered by some to be related to reduced blood flow as a consequence of
      the surgical approach. We measured oxygen concentration during hip resurfacing
      through the trochanteric flip approach (n = 15 patients) and compared this
      approach with previous data for the posterior and anterolateral approaches. With
      the trochanteric flip the average femoral oxygenation decreased during the
      procedure to approximately 50% of that at the start, however it recovered to
      starting level by the end of the procedure. Preservation of oxygenation with the
      trochanteric flip was similar to that observed with the anterolateral approach,
      but with less variation during the procedure. Both of these approaches were
      superior in terms of oxygenation preservation to the posterior approach which
      resulted in a dramatic reduction in oxygenation.

PMID- 18629597
TI  - Musculoskeletal trauma service in Thailand.
AB  - Trauma is becoming a leading cause of death in most of the low-income and middle
      income countries worldwide. The growing number of motor vehicles far surpasses
      the development and upkeep of the road and highway networks, traffic laws, and
      driver training and licensing. In Thailand, road traffic injuries have become the
      second leading cause of death and morbidity overall since 1990. The lack of
      improvement to existing roadways, implementation of traffic safety and ridership
      laws including seatbelt regulations, and poor emergency medical assistance
      support systems all contribute to these statistics. An insufficient number and
      inequitable distribution of healthcare professionals is also a national problem,
      especially at the district level. Prehospital care of trauma patients remains
      insufficient and improvements at the national level are suggested.

PMID- 18629598
TI  - Musculoskeletal trauma services in China.
AB  - China is a developing country with a population over 1.3 billion with the second
      largest group of people in poverty next to India. There are about 159 million
      motor vehicles, with 163,887,372 drivers. From 2001 to 2004 over 100,000 people
      died each year in traffic accidents. With law enforcement and public education,
      traffic accidents have decreased, and the death rate is now less than 100,000
      each year.

PMID- 18629599
TI  - Musculoskeletal trauma services in Uganda.
AB  - Approximately 2000 lives are lost in Uganda annually through road traffic
      accidents. In Kampala, they account for 39% of all injuries, primarily in males
      aged 16-44 years. They are a result of rapid motorization and urbanization in a
      country with a poor economy. Uganda's population is an estimated 28 million with
      a growth rate of 3.4% per year. Motorcycles and omnibuses, the main taxi
      vehicles, are the primary contributors to the accidents. Poor roads and drivers
      compound the situation. Twenty-three orthopaedic surgeons (one for every
      1,300,000 people) provide specialist services that are available only at three
      regional hospitals and the National Referral Hospital in Kampala. The majority of
      musculoskeletal injuries are managed nonoperatively by 200 orthopaedic officers
      distributed at the district, regional and national referral hospitals. Because of
      the poor economy, 9% of the national budget is allocated to the health sector.
      Patients with musculoskeletal injuries in Uganda frequently fail to receive
      immediate care due to inadequate resources and most are treated by traditional
      bonesetters. Neglected injuries typically result in poor outcomes. Possible
      solutions include a public health approach for prevention of road traffic
      injuries, training of adequate human resources, and infrastructure development.

PMID- 18629600
TI  - Recovery from postnatal depression: a consumer's perspective.
AB  - To identify factors that women who have recovered from postnatal depression
      consider to be important in the recovery process and to measure the consensus
      among recovered women regarding the importance of those factors. A two-panel,
      three-round adapted Delphi exercise supplemented by a user-led interpretation
      work-shop. Panel one consisted of ten women who had been treated by a health
      visitor for and recovered from postnatal depression. Panel two consisted of 158
      women who had recovered from postnatal depression who were London based members
      of a national support group for postnatal depression. There was a strong
      consensus among the participants about the 37 success factors that were
      identified. Factors that were identified as 'essential' in recovery from
      postnatal depression included: emotional support from partner; sleep; improved
      communication with partner; the diagnosis; practical support from partner;
      emotional support from friends; time to bond with the new baby; and prompt
      assessment by a health visitor. An interpretation group, made up of seven women
      who had recovered from postnatal depression, condensed the 37 factors into seven
      categories: diagnosis; positive action (or reaction) to intervene in the
      recognized problem; provision of support by people you know; professional or
      outside agency input; relationship between mother and baby; returning to work and
      continuity of care. There was a strong level of consensus among recovered women
      regarding a wide range of recovery factors. While all of the factors were
      considered to be, at least, 'important', social support from family and friends
      was generally rated more highly than support from health care professionals.

PMID- 18629601
TI  - Primary mantle-cell non-Hodgkin's lymphoma of the tongue.
AB  - The evaluation of tongue swellings often represents a diagnostic challenge,
      because of the wide spectrum of benign and malignant possible lesions. We report
      a case of a patient presenting a tongue mass. An incisional biopsy was performed.
      Diagnosis of primary Mantle Cell non-Hodgkin's Lymphoma of the tongue was made by
      histological, immunohistochemical and cytogenetic studies. Our patient was
      treated with Rituximab-Cyclophosphamide, Epirubicine, Vincristine, Prednisone
      polychemotherapy plus Rituximab as single agent maintenance. Complete remission
      was achieved and no relapse has occurred during a follow-up of 53 months. We
      emphasize the importance of including also NHL in differential diagnosis of a
      tongue mass.

PMID- 18629602
TI  - Immunohistochemical study association between human herpesvirus 8 and multiple
      myeloma.
AB  - Multiple myeloma (MM) is a plasma cell neoplasm characterized by a clonal
      proliferation of plasma cells that produce a monoclonal protein and involve the
      skeleton at multiple sites. Although human herpesvirus-8(HHV-8) has been
      implicated in pathogenesis of disease, but this role is not clear. The aim of
      this study was to show direct evidence of HHV-8 in bone marrow tissue of MM
      patients with use of immunohistochemical method. Standard immunohistochemstry was
      performed with HHV-8 marker on formalin fixed paraffin embedded bone marrow
      tissue in 30 MM cases and 30 subjects with normal bone marrow tissue. Slides were
      examined for nuclear immunoreactivity by two pathologists. The data were analyzed
      with 2 x 2 contingency tables and Fischer's exact test, also differences with P
      value under 0.05 (P <or= 0.05) was considered statistically significant. Nuclear
      immunoreactivity for HHV-8 was detected in four patients (13.3%) with MM but was
      not detectable in any normal bone marrow cells. Fisher exact test showed no
      difference for HHV-8 immunoreactivity between two groups of case and control (P =
      0.11). Our finding demonstrated that HHV-8 infection did not seem influence on
      pathogenesis of multiple myeloma.

PMID- 18629603
TI  - A multi-center open-labeled study of recombinant erythropoietin-beta in the
      treatment of anemic patients with multiple myeloma, low-grade non-Hodgkin's
      lymphoma, or chronic lymphocytic leukemia in Chinese population.
AB  - The purpose of this study is to investigate the efficacy and safety of
      recombinant erythropoietin-beta in the treatment of anemic patients with multiple
      myeloma (MM), low-grade non-Hodgkin's lymphoma (NHL), and chronic lymphocytic
      leukemia (CLL). From December 2005 to November 2006, the patients with MM, low
      grade NHL, and CLL were enrolled in this study, male or female, aged > or = 18
      years, transfusion-dependant, and receiving anti-neoplasia chemotherapy.
      Recombinant human erythropoietin-beta was used in this study with the dose
      initiated at 150 IU/kg, thrice a week, subcutaneously. The total treatment
      duration was 12 weeks. The primary endpoint of the study is response rate (RR),
      which is defined as hemoglobin increasing > or = 2 g/dL comparing to baseline
      level, or returning to normal range, without any transfusion within 6 weeks of
      evaluation. Fifty out of 82 (64.6%) patients enrolled in this study responded to
      the treatment and 29 patients had no response. Hypertension (12.2%) is the most
      common adverse effect; however, all the adverse events were mild, categorized in
      NCI grade I or II. We conclude that recombinant erythropoietin-beta was effective
      in the treatment of anemia of the patients with MM, NHL, and CLL, as well as it
      is well-tolerated.

PMID- 18629604
TI  - Isolation, characterization and quantitation of canine alpha-1-acid glycoprotein.
AB  - The present study was designed to investigate the physicochemical properties of
      canine alpha-1-acid glycoprotein (AGP), and to establish a method for measuring
      serum AGP in canine. Fifty-three normal beagles were used in the study. AGP was
      purified from normal canine sera by successive ammonium sulfate precipitation,
      ion-exchange chromatography and gel filtration. The serum AGP concentration was
      measured by single radial immunodiffusion (SRID). Canine AGP had a molecular
      weight of 42,000 +/- 2,000 Da and contained 40.9% carbohydrate. Gel isoelectric
      focusing revealed microheterogeneity with 6-7 bands in a pI range (isoelectric
      points) of 3.2-3.8. AGP migrated to the alpha1-globulin region on
      immunoelectrophoresis. The serum AGP level of 35 normal beagles was 283.4 +/-
      113.3 microg/ml. Canine AGP was isolated, and its physicochemical properties were
      clarified. SRID may be a useful method for quantification of serum AGP in canine.

PMID- 18629605
TI  - L-carnitine mediates protection against DNA damage in lymphocytes of aged rats.
AB  - It has been proposed that age-associated disorders are related to a time
      dependent shift in the antioxidant/prooxidant balance towards oxidative damage.
      Increased production of oxidants in vivo can cause damage to intracellular
      macromolecules such as DNA, proteins and lipids, which can in turn lead to
      oxidative injury. Carnitine is a vitamin-like compound that serves as a carrier
      to transport long-chain fatty acids into the mitochondria for beta-oxidation. In
      the present study, the effect of L-carnitine, a widely recognized essential
      nutrient, was evaluated on the status of lipid peroxidation and certain
      antioxidant enzymes and DNA damage in lymphocytes with relation to age in male
      wistar rats. The levels of lipid peroxides were remarkably increased whereas, the
      activities of antioxidant enzymes were significantly decreased in aged control
      animals when compared to younger controls. In aged animals, administration of L
      carnitine for 21 days significantly decreased the levels of lipid peroxides and
      improved the activities of antioxidant enzymes like superoxide dismutase,
      catalase, glutathione peroxidase and glutathione reductase. L-Carnitine enhanced
      T-cell proliferative responses as evaluated by T-cell proliferation assay using
      [3H] thymidine incorporation and also significantly reduced DNA damage, apoptosis
      and TNF-alpha level in lymphocytes of aged animals. Our results suggest that L 
      carnitine may have a vital role in improving functions in the cells of the immune
      system particularly the lymphocytes possibly through its antioxidant action.

PMID- 18629606
TI  - The activities of PEP carboxylase and the C4 acid decarboxylases are little
      changed by drought stress in three C4 grasses of different subtypes.
AB  - The C4 photosynthetic pathway involves the assimilation of CO2 by
      phosphoenolpyruvate carboxylase (PEPC) and the subsequent decarboxylation of C4
      acids. The enzymes of the CO2 concentrating mechanism could be affected under
      water deficit and limit C4 photosynthesis. Three different C4 grasses were
      submitted to gradually induced drought stress conditions: Paspalum dilatatum
      (NADP-malic enzyme, NADP-ME), Cynodon dactylon (NAD-malic enzyme, NAD-ME) and
      Zoysia japonica (PEP carboxykinase, PEPCK). Moderate leaf dehydration affected
      the activity and regulation of PEPC in a similar manner in the three grasses but
      had species-specific effects on the C4 acid decarboxylases, NADP-ME, NAD-ME and
      PEPCK, although changes in the C4 enzyme activities were small. In all three
      species, the PEPC phosphorylation state, judged by the inhibitory effect of L
      malate on PEPC activity, increased with water deficit and could promote increased
      assimilation of CO2 by the enzyme under stress conditions. Appreciable activity
      of PEPCK was observed in all three species suggesting that this enzyme may act as
      a supplementary decarboxylase to NADP-ME and NAD-ME in addition to its role in
      other metabolic pathways.

PMID- 18629607
TI  - The right ventricle: knowing what is right.

PMID- 18629608
TI  - Bioethics and the sociology of trust: introduction to the theme.

PMID- 18629609
TI  - Trust in early phase research: therapeutic optimism and protective pessimism.
AB  - Bioethicists have long been concerned that seriously ill patients entering early
      phase ('phase I') treatment trials are motivated by therapeutic benefit even
      though the likelihood of benefit is low. In spite of these concerns, consent
      forms for phase I studies involving seriously ill patients generally employ
      indeterminate benefit statements rather than unambiguous statements of unlikely
      benefit. This seeming mismatch between attitudes and actions suggests a need to
      better understand research ethics committee members' attitudes toward
      communication of potential benefits and risks of early phase studies to potential
      subjects. We surveyed the members of two U.S. research ethics committees using a
      phase I gene transfer study scenario, and compared the results to a previous
      survey of potential subjects' perceptions and attitudes toward benefit and risk
      for the same protocol. The results show that there is indeed a gap between the
      subjects' perceptions and the committee members' views on what is appropriate to
      be communicated to research subjects. This discrepancy is the product of both the
      commonly assumed optimism of the subjects and to a "protective pessimism" of the
      research ethics committee members. We discuss this discrepancy using "frameworks
      of trust" and demonstrate the need to incorporate these frameworks into the
      existing model of informed consent.

PMID- 18629610
TI  - Effects of streptozotocin-induced diabetes on connexin43 mRNA and protein
      expression in ventricular muscle.
AB  - Abnormal QT prolongation with the associated arrhythmias is a significant
      predictor of mortality in diabetic patients. Gap junctional intercellular
      communication allows electrical coupling between heart muscle cells. The effects
      of streptozotocin (STZ)-induced diabetes mellitus on the expression and
      distribution of connexin 43 (Cx43) in ventricular muscle have been investigated.
      Cx43 mRNA expression was measured in ventricular muscle by quantitative PCR. The
      distribution of total Cx43, phosphorylated Cx43 (at serine 368) and non
      phosphorylated Cx43 was measured in ventricular myocytes and ventricular muscle
      by immunocytochemistry and confocal microscopy. There was no significant
      difference in Cx43 mRNA between diabetic rat ventricle and controls. Total and
      phosphorylated Cx43 were significantly increased in ventricular myocytes and
      ventricular muscle and dephosphorylated Cx43 was not significantly altered in
      ventricular muscle from diabetic rat hearts compared to controls. Disturbances in
      gap junctional intercellular communication, which in turn may be attributed to
      alterations in balance between total, phosphorylated and dephosporylated Cx43,
      might partly underlie prolongation of QRS and QT intervals in diabetic heart.

PMID- 18629611
TI  - Nitric oxide and MCP-1 regulation in LPS activated rat Kupffer cells.
AB  - Nitric oxide (NO) and Monocyte Chemoattractant Protein (MCP)-1 co-regulation has
      been found in endotoxin-activated macrophages. Kupffer cells (KC) are a main
      source of soluble-mediators production in liver abnormalities. We investigated in
      vitro similar co-regulation of NO and MCP-1 production in rat activated KC.
      Isolated rat KC were cultured in the presence of 1 microg/ml LPS and various
      concentrations of Wortmannin (0-300 nM), L-NAME (0-500 microM) or MCP-1 (0-100
      ng/ml). Production of MCP-1 and NO were measured in supernatants, by ELISA and a
      modification of the Griess reaction, respectively. Growth arrested KC, stimulated
      with vehicle, produced a basal amount of NO and MCP-1. In the presence of LPS,
      cultured KC secreted significantly (P < 0.01) increased amounts of MCP-1 and NO.
      Pre-treatment of KC with various concentrations of L-NAME significantly (P <
      0.05) reduced the LPS-induced secretion of NO in a concentration dependent
      manner, but the MCP-1 production remained unaffected. Pre-treatment with
      Wortmannin significantly (P < 0.05) inhibited LPS-induced secretion of MCP-1 and
      NO in a concentration dependent manner. Linear regression analysis revealed a
      positive correlation between MCP-1 and NO in the LPS (r = 0.59171, P < 0.0001)
      and Wortmannin (r = 0.9215, P = 0.009) treated groups, but not in the L-NAME (r =
      -0.08513, P = 0.873). Incubation of KC with various concentrations of MCP-1 did
      not increase the NO production. These results indicate that KC might be the main
      source of NO and MCP-1 production in liver disorders, probably through the
      induction of PI3-kinase(s) and without any co-regulation between these molecules,
      which might represent two independent immunoregulatory pathways in the role of KC
      in hepatic disorders.

PMID- 18629612
TI  - Expression, purification, and reconstitution of the Na(+)/H (+) exchanger sod2 in
      Saccharomyces cerevisiae.
AB  - Sod2, is a Na(+)/H(+) exchanger present on the cytoplasmic membrane of the
      fission yeast Schizosaccharomyces pombe. It expels toxic Na(+) from the cytosol.
      Sod2 was expressed in Saccharomyces cerevisiae with a C-terminal histidine tag
      under control of the GAL1 promoter. Western blots using anti-V5 antibodies
      identified the tagged protein. Solubilization of the protein was by n-dodecyl
      beta-D: -maltoside. Immobilized Ni-ion column affinity chromatography partially
      purified the protein at a yield of ~240 microg per liter of culture. Sod2 was
      present as a 40-kDa and an 80-kDa protein, however, it co-purified with a number
      of other proteins. Cross linking of sod2 with N,N'-(o-phenylene)dimaleimide
      showed that sod2 was present in association with a number of other proteins as a
      larger molecular weight complex. Partially purified sod2 protein was
      reconstituted in proteoliposomes and functionally active. Our results suggest
      that the sod2 protein associates with a number of other proteins and can be
      expressed in S. cerevisiae in active form.

PMID- 18629613
TI  - PHB2 interacts with RNF2 and represses CP2c-stimulated transcription.
AB  - RNF2, a polycomb group protein, is an important component of PRC complex
      regulating transcriptional activity. Recently, several RNF2 interacting proteins
      have been identified. Thus, RNF2 might have multiple activities, depending on its
      interacting partner proteins. In the present study, using the yeast two-hybrid
      system, we have found that RNF2 interacts with the PHB2 protein. Luciferase
      reporter assays showed that RNF2 represses the CP2c-stimulated luciferase
      activity in a PHB2 dose-dependent manner. Further experiments with RNF2 deletion
      mutants indicated that RNF2(1-158) is sufficient for both the physical
      association and functional co-operation with the PHB2 protein. Co
      immunoprecipitation experiments revealed that PHB2 and CP2c bind to the N- and C
      terminals of RNF2, respectively. Luciferase reporter assays using alpha-globin
      promoter with CP2-binding elements hinted that RNF2 and PHB2 are involved in the
      CP2-stimulated expression of the alpha-globin gene. Our study suggests a novel
      mechanism by which RNF2 and PHB2 modulate the CP2-mediated transcriptional
      pathway.

PMID- 18629614
TI  - Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat
      hepatocellular carcinoma.
AB  - One of the focuses in current cancer chemoprevention studies is the search for
      nontoxic chemopreventive agents that inhibit the initiation of malignant
      transformation. Cancer biomarkers are quantifiable molecules involved in the
      physiologic or pathologic events occurring between exposure to carcinogens and
      the development, progression of cancer. Biomarkers may be the consequence of a
      continuous process, such as increased cell mass, or a discrete event, such as
      genetic mutation. Analysis of tumor markers can be used as an indicator of tumor
      response to therapy. Gallic acid is a naturally available polyphenol, possess
      strong antioxidant activity with a capacity to inhibit the formation of tumors in
      several cancer models. In the present study, we investigated the
      antiproliferative effect of gallic acid during diethylnitrosamine (DEN)-induced
      hepatocellular carcinoma (HCC) in male wistar albino rats. DEN treatment resulted
      in increased levels of aspartate transaminase, alanine transaminase, alkaline
      phosphatase, acid phosphatase, lactate dehydrogenase, gamma-glutamyltransferase,
      5'-nucleotidase, bilirubin, alpha-fetoprotein, carcinoembryonic antigen,
      argyophillic nucleolar organizing regions, and proliferating cell nuclear
      antigen. Gallic acid treatment significantly attenuated these alterations and
      decreased the levels of AgNORs and PCNA. These finding suggests that gallic acid
      is a potent antiproliferative agent against DEN-induced HCC.

PMID- 18629615
TI  - Association of angiotensin-converting enzyme and endothelial Nitric Oxide
      synthase gene polymorphisms with vascular disease in ESRD patients in a Chinese
      population.
AB  - BACKGROUND: The effect of angiotensin-converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism and endothelial Nitric Oxide synthase
      (eNOS) gene G894 --> T on vascular disease in end-stage renal disease (ESRD)
      patients was rarely studied previously. We investigated such effect in a Chinese
      population. METHODS: A total of 153 ESRD patients with vascular disease (88 men
      and 65 women; mean age +/- SD: 54.0 +/- 13.2) were recruited. Polymerase chain
      reaction was used to classify the ACE genotypes as II, ID and DD and the eNOS
      genotypes as GG, GT, and TT. Analyses were performed in ESRD patients with
      vascular disease (n = 153) and the age-matched controls (n = 148). RESULTS: The
      frequencies of ACE DD and eNOS TT genotypes and ACE D and eNOS T alleles in ESRD
      patients with vascular disease were significantly higher than those in the
      controls (P < 0.05). There was a significant interaction between ACE I/D alleles
      and eNOS G894 --> T polymorphism: adjusted odds ratio 2.128 (95%CI 1.022-4.434, P
      = 0.017). CONCLUSIONS: These results indicated that the etiology of vascular
      disease in ESRD patients is associated with ACE and eNOS (G894 --> T) gene
      polymorphisms. Our data also suggest that an interaction effect may exist between
      ACE (I/D) and eNOS (G894 --> T) polymorphism in increasing the risk of vascular
      complications in ESRD patients.

PMID- 18629617
TI  - Biological response of human bone marrow stromal cells to sandblasted titanium
      nitride-coated implant surfaces.
AB  - Titanium nitride (TiN) coating has been proposed as an adjunctive surface
      treatment aimed to increase the physico-mechanical and aesthetic properties of
      dental implants. In this study we investigated the biological response of primary
      human bone marrow stromal cells (BMSC) to TiN-coated sandblasted (TiN-SB)
      compared to uncoated sandblasted (SB) surfaces. SB and TiN-SB disks were
      qualitatively and quantitatively analyzed by atomic force microscopy. BMSC were
      obtained from healthy donors and their adhesion and proliferation on the titanium
      disks were evaluated by scanning electron microscopy and viability assay. The
      osteoblastic differentiation, in terms of alkaline phosphatase activity,
      osteocalcin synthesis, and extracellular mineralization, was assessed by specific
      immunoenzymatic or spectrophotometric assays. No difference (P > 0.05) between
      TiN-SB and SB disks was found in terms of any of the investigated parameters. TiN
      coating showed to maintain the topographical characteristics of sandblasted
      titanium surfaces and their biological affinity toward bone precursors.

PMID- 18629616
TI  - Regulation of respiration in brain mitochondria and synaptosomes: restrictions of
      ADP diffusion in situ, roles of tubulin, and mitochondrial creatine kinase.
AB  - The role of ubiquitous mitochondrial creatine kinase (uMtCK) reaction in
      regulation of mitochondrial respiration was studied in purified preparations of
      rat brain synaptosomes and mitochondria. In permeabilized synaptosomes, apparent
      Km for exogenous ADP, Km (ADP), in regulation of respiration in situ was rather
      high (110 +/- 11 microM) in comparison with isolated brain mitochondria (9 +/- 1
      microM). This apparent Km for ADP observed in isolated mitochondria in vitro
      dramatically increased to 169 +/- 52 microM after their incubation with 1 muM of
      dimeric tubulin showing that in rat brain, particularly in synaptosomes,
      mitochondrial outer membrane permeability for ADP, and ATP may be restricted by
      tubulin binding to voltage dependent anion channel (VDAC). On the other hand, in
      synaptosomes apparent Km (ADP) decreased to 25 +/- 1 microM in the presence of 20
      mM creatine. To fully understand this effect of creatine on kinetics of
      respiration regulation, complete kinetic analysis of uMtCK reaction in isolated
      brain mitochondria was carried out. This showed that oxidative phosphorylation
      specifically altered only the dissociation constants for MgATP, by decreasing
      that from ternary complex MtCK.Cr.MgATP (K (a)) from 0.13 +/- 0.02 to 0.018 +/-
      0.007 mM and that from binary complex MtCK.MgATP (K (ia)) from 1.1 +/- 0.29 mM to
      0.17 +/- 0.07 mM. Apparent decrease of dissociation constants for MgATP reflects
      effective cycling of ATP and ADP between uMtCK and adenine nucleotide translocase
      (ANT). These results emphasize important role and various pathophysiological
      implications of the phosphocreatine-creatine kinase system in energy transfer in
      brain cells, including synaptosomes.

PMID- 18629618
TI  - The impact of aqueous solubility and dose on the pharmacokinetic profiles of
      resveratrol.
AB  - PURPOSE: This study aimed at the investigation of the impact of aqueous
      solubility and dose manipulation on the pharmacokinetics of resveratrol. METHODS:
      Water soluble intravenous and oral formulations of resveratrol were prepared with
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and randomly methylated-beta
      cyclodextrin (RM-beta-CD), respectively. Sodium salt and suspension of
      resveratrol in carboxymethyl cellulose (CMC) were used as the reference
      intravenous and oral formulations, respectively. The pharmacokinetics of
      resveratrol was assessed in Sprague-Dawley rats. Plasma resveratrol
      concentrations were measured by high performance liquid chromatography (HPLC).
      RESULTS: Both HP-beta-CD and RM-beta-CD enhanced the aqueous solubility of
      resveratrol. After intravenous administration, rapid elimination of resveratrol
      was observed at all tested doses (5, 10, and 25 mg kg(-1)) regardless of
      formulation types; with non-linear elimination occurring at the dose of 25 mg kg(
      1). RM-beta-CD significantly increased the maximal plasma concentration of orally
      administered resveratrol, but, it did not increase the oral bioavailability in
      comparison with the CMC suspension. Furthermore, the oral bioavailability
      remained unchanged among all tested doses (15, 25, and 50 mg kg(-1)).
      CONCLUSIONS: Aqueous solubility barrier might affect the speed but not the extent
      of resveratrol absorption. Further, dose manipulation (up to 50 mg kg(-1)) did
      not have a significant impact on the oral bioavailability of resveratrol.

PMID- 18629619
TI  - The CCR5 (-2135C/T) polymorphism may be associated with the development of
      Kawasaki disease in Korean children.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute vasculitis syndrome of unknown
      etiology that frequently affects small to medium size arteries. C-C chemokine
      receptor 5 (CCR5) is a chemokine receptor that binds C-C chemokines. This study
      investigated the association of the CCR5 (-2135C/T) polymorphism with KD in
      Korean children. METHODS: The study population consisted 189 Korean children with
      KD and 194 Korean children with congenital heart disease (CHD). CCR5 (-2135C/T)
      polymorphism genotypes were determined using the single-base extension method.
      RESULTS: The allele frequencies of the CCR5 (-2135C/T) polymorphism differed
      significantly between CHD children and KD children (-2135T/T, 16.75% vs. 30.05%,
      aOR 2.14, 95% CI 1.31-3.51). The tested laboratory parameters differed
      significantly between the KD and CHD groups. The development of coronary artery
      aneurysm in KD patients was not associated with the CCR5 polymorphism.
      CONCLUSIONS: Our findings suggest that the T allele at the CCR5 (-2135C/T)
      polymorphism might be associated with the development of KD in Korean children
      but does not appear to be associated with the development of coronary artery
      aneurysm.

PMID- 18629620
TI  - The dynamic prediction of criminal recidivism: a three-wave prospective study.
AB  - A three-wave, prospective panel design was used to assess the extent to which
      static and dynamic risk factors could predict criminal recidivism in a sample of
      136 adult male offenders released from Canadian federal prisons. Static measures
      were assessed only once, prior to release while dynamic measures were assessed on
      three separate occasions: pre-release, 1 month, and 3 months post-release.
      Recidivism was coded during an average of 10.2-month follow-up period (SD=19.2).
      A series of Cox regression survival analyses with time-dependent covariates and
      Receiver Operator Characteristic (ROC) analyses were conducted to assess
      predictive validity. Although the combined static and time-dependent dynamic
      model (AUC=.89, CI=.81-.93) significantly (p<.01) outperformed the pure static
      model (AUC=.81, CI=.73-.87) the confidence intervals did overlap to some extent.
      Implications for dynamic risk assessment and management are discussed.

PMID- 18629621
TI  - Do sociodemographic characteristics of pregnant women determine their perception
      of antenatal care quality?
AB  - OBJECTIVES: To explore sociodemographic determinants of perceived quality of
      antenatal care (ANC) at the primary care level. METHODS: A survey of 452 randomly
      selected pregnant women accessing antenatal care at the primary healthcare
      facilities in Sagamu Local Government Area (LGA) of Ogun State, southwest
      Nigeria. The relationships between 13 sociodemographic characteristics of women
      and their overall perception of the quality of care (expressed by their level of
      overall satisfaction) were examined through bivariate analyses, by computing odds
      ratio at 95% confidence interval. Multivariate logistic regression analyses were
      used to determine independent sociodemographic determinants of overall
      satisfaction with quality of care received. A P-value <0.05 or CI which did not
      embrace unity was considered as statistical significance. RESULTS: From bivariate
      analyses, increasing parity, increasing number of living children, gainful
      employment of client and Islamic religion increases the likelihood of positive
      perception of antenatal care quality. Characteristics such as age, being married,
      women's monthly earning, ethnicity, employment status of husband, educational
      level, duration of pregnancy, frequency of antenatal visits, and previous use of
      antenatal care at the same centre were not associated with overall satisfaction
      with antenatal care quality. Independent predictors from multivariate regression
      analyses include parity (adjusted OR 0.13; CI: 0.05-0.33, P = 0.005) and religion
      (other religions vs. Islam; adjusted OR: 0.14, CI: 0.04-0.40, P = 0.0003).
      CONCLUSIONS: The study suggests that sociodemographic characteristics of women
      have limited impact on their perception of ANC quality. The identified predictors
      may serve as the criteria for selecting women that require intensive health
      centre-specific antenatal interventions aimed at improving perceived quality and
      thus sustained utilization of antenatal care services in these primary health
      care facilities.

PMID- 18629622
TI  - Mobilizing bone marrow progenitor cells, a double edge sword.

PMID- 18629623
TI  - Sensori-motor and daily living skills of preschool children with autism spectrum
      disorders.
AB  - Sensori-motor development and performance of daily living skills (DLS) remain
      little explored in children with autism spectrum disorders (ASD). The objective
      of this study was to determine the impact of sensori-motor skills on the
      performance of DLS in preschool children with ASD. Thirty-five children, 3-4
      years of age, were recruited and assessed with a battery of diagnostic and
      clinical tests. Children showed atypical sensory responses, very poor motor and
      DLS. Sensory avoiding, an excessive reaction to sensory stimuli, and fine motor
      skills were highly correlated with DLS, even when cognitive performance was taken
      into account. Sensori-motor deficits have an impact on the autonomy of children
      with ASD and interventions should aim at improving and supporting the development
      of sensori-motor skills.

PMID- 18629624
TI  - Sex differences in WISC-III profiles of children with high-functioning pervasive
      developmental disorders.
AB  - Using the Japanese version of the Wechsler Intelligence Scale for Children-Third
      Edition (WISC-III), 26 girls with high-functioning (IQ > or = 70) pervasive
      developmental disorders (HFPDD) (mean age, 8.2 years) were compared with 116 boys
      with HFPDD (mean age, 9.0 years). Compared with the boys, the girls scored
      significantly higher on the Processing Speed index, Coding, and Symbol Search,
      but scored significantly lower on Block Design. Although both groups showed
      weakness on Comprehension in the verbal domain, the girls' subtest profile in the
      performance domain was relatively even and significantly different from the
      boys', which was characterized by a peak on Block Design. Such differences should
      be replicated, and possible behavioral, neurological, and genetic links to these
      sex differences should be clarified.

PMID- 18629625
TI  - Cortical imaging on a head template: a simulation study using a resistor mesh
      model (RMM).
AB  - The T1 head template model used in Statistical Parametric Mapping Version 2000
      (SPM2), was segmented into five layers (scalp, skull, CSF, grey and white matter)
      and implemented in 2 mm voxels. We designed a resistor mesh model (RMM), based on
      the finite volume method (FVM) to simulate the electrical properties of this head
      model along the three axes for each voxel. Then, we introduced four dipoles of
      high eccentricity (about 0.8) in this RMM, separately and simultaneously, to
      compute the potentials for two sets of conductivities. We used the direct
      cortical imaging technique (CIT) to recover the simulated dipoles, using 60 or
      107 electrodes and with or without addition of Gaussian white noise (GWN). The
      use of realistic conductivities gave better CIT results than standard
      conductivities, lowering the blurring effect on scalp potentials and displaying
      more accurate position areas when CIT was applied to single dipoles. Simultaneous
      dipoles were less accurately localized, but good qualitative and stable
      quantitative results were obtained up to 5% noise level for 107 electrodes and up
      to 10% noise level for 60 electrodes, showing that a compromise must be found to
      optimize both the number of electrodes and the noise level. With the RMM defined
      in 2 mm voxels, the standard 128-electrode cap and 5% noise appears to be the
      upper limit providing reliable source positions when direct CIT is used. The
      admittance matrix defining the RMM is easy to modify so as to adapt to different
      conductivities. The next step will be the adaptation of individual real head T2
      images to the RMM template and the introduction of anisotropy using diffusion
      imaging (DI).

PMID- 18629626
TI  - Altered pattern of Na,K-ATPase activity and mRNA during chronic alcohol
      consumption by juvenile and adolescent rats.
AB  - The effect of chronic ethanol consumption on cerebral cortical activity of Na,K
      ATPase was determined in Long-Evans (LE) rats fed an ethanol-containing diet
      beginning at different stages of development. Na,K-ATPase activity was
      operationally resolved into alpha1 and alpha2/3 isozyme activities. There was no
      significant difference in Na,K-ATPase activities before and after alcohol
      consumption in the preparations from adult rats. However, for rats beginning
      alcohol consumption as adolescents, the alpha2/3 activity was significantly
      elevated following chronic alcohol consumption. Both LE and Sprague-Dawley rats
      showed this same selective increase in cortical alpha2/3 activity when rats began
      alcohol consumption as juveniles. The shift in cortical alpha2/3 activity was not
      observed in cerebellum or subcortical forebrain and was reversible when rats were
      fed ethanol throughout the normal adolescent period and then withdrawn and tested
      2 weeks later (during the adult period). Levels of isoform-specific mRNA were
      determined in preparations of cerebral cortices of rats showing elevated alpha2/3
      isozyme activities. In these preparations, isoform specific alpha2 and alpha3
      mRNA was significantly elevated. There was no effect of ethanol feeding on
      cortical alpha1 mRNA. These findings indicate that the longer term effects of
      ethanol on the developing brain include elevated Na,K-ATPase activity and a
      mechanism that is pre-translational and isoform specific.

PMID- 18629627
TI  - DIXDC1 promotes retinoic acid-induced neuronal differentiation and inhibits
      gliogenesis in P19 cells.
AB  - Human DIXDC1 is a member of Dishevelled-Axin (DIX) domain containing gene family
      which plays important roles in Wnt signaling and neural development. In this
      report, we first confirmed that expression of Ccd1, a mouse homologous gene of
      DIXDC1, was up-regulated in embryonic developing nervous system. Further studies
      showed that Ccd1 was expressed specifically in neurons and colocalized with early
      neuronal marker Tuj1. During the aggregation induced by RA and neuronal
      differentiation of embryonic carcinoma P19 cells, expressions of Ccd1 as well as
      Wnt-1 and N-cadherin were dramatically increased. Stable overexpression of DIXDC1
      in P19 cells promoted the neuronal differentiation. P19 cells overexpressing
      DIXDC1 but not the control P19 cells could differentiate into Tuj1 positive cells
      with RA induction for only 2 days. Meanwhile, we also found that overexpression
      of DIXDC1 facilitated the expression of Wnt1 and bHLHs during aggregation and
      differentiation, respectively, while inhibited gliogenesis by down-regulating the
      expression of GFAP in P19 cells. Thus, our finding suggested that DIXDC1 might
      play an important role during neurogenesis, overexpression of DIXDC1 in embryonic
      carcinoma P19 cells promoted neuronal differentiation, and inhibited gliogenesis
      induced by retinoic acid.

PMID- 18629628
TI  - Tissue plasminogen activator enhances the hypoxia/reoxygenation-induced
      impairment of the blood-brain barrier in a primary culture of rat brain
      endothelial cells.
AB  - Hemorrhagic transformation is a major complication associated with tissue
      plasminogen activator (tPA) therapy for ischemic stroke. We studied the effect of
      tPA on the blood-brain barrier (BBB) function with our in vitro monolayer model
      generated using rat brain microvascular endothelial cells subjected either to
      normoxia or to hypoxia/reoxygenation (H/R) with or without the administration of
      tPA. The barrier function was evaluated by the transendothelial electrical
      resistance (TEER), the permeability of sodium fluorescein and Evans' blue-albumin
      (EBA), and the uptake of lucifer yellow (LY). The permeability of sodium
      fluorescein and EBA was used as an index of paracellular and transcellular
      transport, respectively. The administration of tPA increased the permeability of
      EBA and the uptake of LY under normoxia. It enhanced the increase in the
      permeability of both sodium fluorescein and EBA, the decrease in the TEER, and
      the disruption in the expression of ZO-1 under H/R conditions. Administration of
      tPA could cause an increase in the transcellular transport under normoxia, and
      both the transcellular and paracellular transport of the BBB under H/R conditions
      in vitro. Even in humans, tPA may lead to an opening of the BBB under non
      ischemic conditions and have an additional effect on the ischemia-induced BBB
      disruption.

PMID- 18629629
TI  - Association of genetic polymorphisms of ER-alpha and the estradiol-synthesizing
      enzyme genes CYP17 and CYP19 with breast cancer risk in Chinese women.
AB  - Estrogen plays a role in breast cancer development, and genetic polymorphisms in
      estrogen receptor gene ER-alpha and genes regulating estrogen biosynthesis and
      metabolisms are associated with the risk of breast cancer in women in western
      countries. Therefore, we hypothesized that SNPs in ER-alpha and other estrogen
      metabolizing genes contribute to breast cancer risk in Chinese women. In this
      study, we genotyped polymorphisms in the regulatory regions of ER-alpha
      (rs3798577) and other two estrogen-metabolizing enzyme genes CYP17 (rs743572) and
      CYP19 (rs10046) among 300 breast cancer cases and 390 controls in a Chinese
      population. Crude and adjusted odds ratios (aORs) and 95% confidence intervals
      (CIs) were calculated by unconditional logistic regression analyses to estimate
      breast cancer risk associated with these polymorphisms. We found that the T
      allele frequency of ER-alpha was significantly higher in cases (59.8%) than
      controls (54.5%) (P = 0.047), but no significant difference was found in the
      genotype distribution. However, postmenopausal breast cancer risk was associated
      with the CYP17 TC genotype (aOR = 1.77, 95% CI = 1.11-2.83) compared with the TT
      genotype. The CYP19 variant TC + TT genotypes were associated with both overall
      cancer risk (TT + TC vs. TT aOR = 1.73, 95% CI = 1.13-2.65) and premenopausal
      cancer risk (TT + TC vs. TT aOR = 1.78, 95% CI = 1.03-3.09), particularly for ER
      +/PR + tumors. Furthermore, there were joint effects between CYP19 T and ER-alpha
      T variant genotypes (aOR = 1.67, 95% CI = 1.03-2.69 for CYP19 TC + TT vs. CC
      among ER-alpha T variant carriers) and between CYP19 T and CYP17 C variant
      genotypes (aOR = 1.77, 95% CI = 1.11-2.83 for CYP19 TC + TT vs. CC among CYP17
      variant C carriers). This study provides evidence that polymorphisms CYP17
      rs743572, CYP19 rs10046 and ER-alpha rs3798577 are associated with breast cancer
      risk among Chinese women.

PMID- 18629630
TI  - Downregulation of SIAH2, an ubiquitin E3 ligase, is associated with resistance to
      endocrine therapy in breast cancer.
AB  - PURPOSE: In our microarray analysis we observed that Seven-in-Absentia Homolog 2
      (SIAH2) levels were low in estrogen receptor (ER) positive breast tumors of
      patients resistant to first-line tamoxifen therapy. The aim of this study was to
      evaluate SIAH2 for its (a) predictive/prognostic value, and (b) functional role
      in endocrine therapy resistance. PATIENTS AND METHODS: SIAH2 expression was
      measured with quantitative Real-Time-PCR (qRT-PCR) in 1205 primary breast tumor
      specimens and related to disease outcome. The functional role of SIAH2 was
      determined in human breast cancer cell lines ZR-75-1, ZR/HERc, and MCF7. Cell
      lines were treated with estrogen (E2), anti-estrogen ICI164.384 or epidermal
      growth factor (EGF). Moreover, MCF7 was treated with ICI164.384 after silencing
      SIAH2 expression. RESULTS: SIAH2 was not prognostic in 603 lymph node negative
      patients who had not received adjuvant systemic therapy. In multivariate analysis
      of ER-positive tumors of 235 patients with recurrent disease, SIAH2 as continuous
      variable, significantly predicted first-line tamoxifen treatment failure (OR =
      1.48; P = 0.05) and progression-free survival (PFS) (HR = 0.79; P = 0.007).
      Furthermore, in primary breast cancer patients treated with adjuvant tamoxifen,
      SIAH2 predicted metastasis-free survival (MFS) (HR = 0.73; P = 0.005). In vitro
      experiments showed that SIAH2 silencing in MCF7 cells resulted in resistance to
      ICI164.384-treatment when compared with mock silenced cells (P = 0.008).
      Interestingly, in ZR cells transfected with EGFR (ZR/HERc), SIAH2 expression was
      induced by E2 but downregulated by EGF. CONCLUSION: In primary breast tumor
      specimens as well as in vitro low SIAH2 levels associated with resistance to
      endocrine therapy. Moreover, SIAH2 expression showed an opposite regulation by E2
      and EGF.

PMID- 18629631
TI  - Pharmaceuticals that cause mammary gland tumors in animals: findings in women.
AB  - Risk of breast cancer in women was assessed for eight pharmaceuticals that
      produce mammary tumors in experimental animals, using nested case-control
      analyses in two cohorts with prescription records in a comprehensive medical care
      program. The two cohorts were: (1) earlier cohort: 78,118 female members who
      received prescriptions in 1969-1973, of whom 2,467 developed breast cancer, and
      (2) later cohort: 3,289,408 female members who received prescriptions in 1994
      2006 of whom 24,528 developed breast cancer. Longest follow-up was until June 30,
      2006. Ten randomly selected concurrent control women were age-matched to almost
      every case. Relative risks were estimated by conditional logistic regression.
      Case ascertainment was lagged by 2 years, or unlagged and subdivided by number of
      prescriptions received. Some analyses were controlled for hormone use and
      sensitivity analyses were conducted to estimate the effects of uncontrolled
      confounding. In the later cohort furosemide, and metronidazole showed
      statistically significant but very small increases in relative risk (ranging from
      1.07 to 1.13). Of these, only furosemide showed increased risk in the earlier
      cohort: 2-year lag relative risk 1.66 (95% confidence interval 1.23-2.24) or as
      low as 0.97, assuming uncontrolled positive confounding. Griseofulvin showed
      significant increases in the later cohort: relative risk for three or more
      prescriptions 1.48 (1.08-2.03) or as low as 1.23 assuming uncontrolled positive
      confounding and non-significant increases were noted in the earlier cohort. Our
      findings are limited by their inconsistency across the two cohorts and our
      inability to directly control for most established breast cancer risk factors.
      Although inconclusive, our findings suggest a need for more research on
      furosemide and griseofulvin.

PMID- 18629632
TI  - Triple-negative breast cancers express receptors for growth hormone-releasing
      hormone (GHRH) and respond to GHRH antagonists with growth inhibition.
AB  - Triple-negative breast cancers do not express receptors for estrogen or
      progesterone and do not overexpress HER2. These tumors have an unfavorable
      prognosis and at present chemotherapy is the only treatment option. Because the
      antagonists of growth hormone-releasing hormone (GHRH) have been shown to inhibit
      growth of a variety of cancers by endocrine and paracrine/autocrine mechanisms,
      we evaluated the expression of GHRH receptors in human specimens of triple
      negative breast cancers and the response to GHRH by in vitro models. In samples
      of triple-negative breast cancers we found mRNA expression for the GHRH receptor
      and its functional splice variant SV1 in 25 and 70% of the cases, respectively
      and for GHRH in 80% of the samples. Immunoreaction of SV1 was detected in the
      human triple-negative breast cancer cell line HCC1806 while HCC1937 was negative.
      The growth of HCC1806 was stimulated by GHRH(1-44)NH(2) and inhibited by GHRH
      antagonist MZ-J-7-118. In addition, in HCC1806 MAP-kinases ERK-1/2 were activated
      by GHRH. Our findings suggest the existence of an autocrine loop consisting of
      GHRH and GHRH receptors in triple-negative breast cancers. Our in vitro studies
      demonstrate that targeting the GHRH receptor may be a therapeutic option which
      should be evaluated in studies in vivo.

PMID- 18629633
TI  - Cognitive impairments associated with breast cancer treatments: results from a
      longitudinal study.
AB  - PURPOSE: Published cross-sectional studies have revealed that chemotherapy for
      breast cancer is associated with significant cognitive impairments. However,
      because these studies included no baseline assessment, it is unknown whether the
      cognitive impairments were pre-existent to cancer treatment or truly secondary to
      chemotherapy. To resolve this issue, this prospective study aimed to compare the
      effects of chemotherapy to the effect of radiotherapy on cognitive functioning in
      women treated for non-metastatic breast cancer. PATIENTS AND METHODS: A total of
      81 breast cancer patients, 41 receiving chemotherapy as part of their breast
      cancer treatment regimen and 40 receiving radiotherapy without chemotherapy were
      evaluated using an extensive battery of neuropsychological tests at baseline (ie,
      pre-chemotherapy or pre-radiotherapy), post-treatment (ie, post-chemotherapy or
      post-radiotherapy) and at a 3-month follow-up assessment. RESULTS: A mixed model
      covariance analysis revealed that receiving any kind of breast cancer treatment,
      with chemotherapy or not, was associated with impaired capacities for recruiting
      information in verbal memory. Moreover, the results showed that verbal fluency
      was impaired after breast cancer treatment, but only in patients who received
      chemotherapy. CONCLUSION: Overall, this study reveals subtle cognitive
      impairments associated with breast cancer treatment. Specifically, it suggests
      that chemotherapy has a specific negative effect on verbal fluency, that breast
      cancer treatment in general negatively affects verbal memory, but that other
      cognitive functions are well preserved. Future studies should, however, attempt
      to better control the practice effect that may have masked other subtle
      alterations and use more ecologically valid measures of cognitive functioning.

PMID- 18629634
TI  - Lack of prognostic significance of "classic" lobular breast carcinoma: a matched,
      single institution series.
AB  - Whether invasive lobular carcinoma of the breast per se constitutes a
      prognostically favorable type has been debated. The present series comprises 301
      consecutive "classic" lobular breast carcinomas seen at one institution between
      1994 and 2001, compared to an equal number of invasive ductal carcinomas at the
      same institution during the same period, matched for year of surgery, age,
      menopausal status, primary tumor size, nodal involvement, hormone receptor status
      and where possible histological grade. Despite matching, the lobular carcinomas
      were more frequently multifocal, had more involved nodes, lower grade and lower
      proliferative fraction. There was no significant difference in disease-free or
      overall survival, locoregional relapse or time to distant metastasis between the
      lobular and ductal groups overall or within any examined subset, though the
      lobular group showed a trend to earlier appearance of contralateral breast
      cancer. Classical lobular histology is not an independent factor in the prognosis
      of early breast cancer.

PMID- 18629635
TI  - Short-term outcome of primary operated early breast cancer by hormone and HER-2
      receptors.
AB  - INTRODUCTION: Prognostic subgroup classification of operable breast cancers using
      cDNA clustering of breast cancer-related genes resembles the classification based
      on the combined immunohistochemical (IHC) expression of the hormone and HER-2
      receptors. We here report the short-term disease-free interval (DFI) of operable
      breast cancers by their joint hormone receptor/HER-2 phenotype. PATIENTS AND
      METHODS: Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancer
      patients primary operated at our institution between 2000 and 2005. Receptors
      were evaluated using IHC. Steroid receptors were considered positive for any
      nuclear staining; HER-2 for strong (3+) membrane staining or positive
      fluorescence in situ hybridization (FISH). Kaplan-Meier (KM) DFI curves were
      calculated for any relapse defined as a local, regional, contralateral, or
      distant breast cancer event for the six predefined breast cancer subgroups: ER +
      PR + HER-2 - (PPN), ER + PR - HER-2 - (PNN), ER + PR + HER-2 + (PPP), ER - PR -
      HER-2 - (NNN), ER - PR - HER-2 + (NNP), and ER + PR - HER-2 + (PNP). P-values
      were calculated for comparison of the six different survival curves using two
      possible adaptations for multiple testing. A multivariate model for the receptors
      predicting DFI did incorporate local and systemic adjuvant therapy. RESULTS:
      Median patient age was 57 years (ranges 26-96) and median FU was 3.35 years.
      Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for
      PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a
      significantly better DFI than others based on multiple testing, especially when
      the PPN group was compared against the four most frequent subtypes. The
      multivariate model with local and systemic adjuvant therapy confirmed the
      prognostic value of ER, PR, and HER-2 for short-term DFI. CONCLUSION: It is
      possible to distinguish short-term prognostic breast cancer subgroups only on the
      basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant
      therapy. While gene expression profiles based on microarray data of over hundreds
      of genes will probably teach us much about breast cancer biology, heterogeneity,
      and prognosis, we emphasize the important short-term prognostic value of
      currently used IHC markers for ER, PR, and HER-2.

PMID- 18629636
TI  - Effect of hydrogen sulfide on sympathetic neurotransmission and catecholamine
      levels in isolated porcine iris-ciliary body.
AB  - In the present study, we investigated the pharmacological action of hydrogen
      sulfide (H2S, using sodium hydrosulfide, NaHS, and/or sodium sulfide, Na2S as
      donors) on sympathetic neurotransmission from isolated, superfused porcine iris
      ciliary bodies. We also examined the effect of H2S on norepinephrine (NE),
      dopamine and epinephrine concentrations in isolated porcine anterior uvea.
      Release of [3H]NE was triggered by electrical field stimulation and basal
      catecholamine concentrations was measured by high performance liquid
      chromatography (HPLC). Both NaHS and Na2S caused a concentration-dependent
      inhibition of electrically evoked [3H]NE release from porcine iris-ciliary body
      without affecting basal [3H]NE efflux. The inhibitory action of H2S donors on NE
      release was attenuated by aminooxyacetic acid (AOA) and propargyglycine (PAG),
      inhibitors of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase
      (CSE), respectively. With the exception of dopamine, NaHS caused a concentration
      dependent reduction in endogenous NE and epinephrine concentrations in isolated
      iris-ciliary bodies. We conclude that H2S can inhibit sympathetic
      neurotransmission from isolated porcine anterior uvea, an effect that is
      dependent, at least in part, on intramural biosynthesis of this gas. Furthermore,
      the observed action of H2S donors on sympathetic transmission may be due to a
      direct action of this gas on neurotransmitter pools.

PMID- 18629637
TI  - Fluorocitrate, an inhibitor of glial metabolism, inhibits the up-regulation of
      NOS expression, activity and NO production in the spinal cord induced by formalin
      test in rats.
AB  - Previous experiments have suggested that nitric oxide plays an important role in
      nociceptive transmission in the spinal cord. In order to explore the involvement
      of glia in the NO-mediated nociceptive transmission, the present study was
      undertaken to investigate the effect of fluorocitrate (FC), an inhibitor of glial
      metabolism, on NOS expression and activity and NO production in the spinal cord
      during the process of peripheral inflammatory pain and hyperalgesia induced by
      formalin test in rats. Sixty adult male Sprague-Dawley rats were randomly
      assigned into sham, formalin, formalin + normal saline (NS), and formalin + FC
      groups. The NOS expression, NOS activity and NO production was detected by NADPH
      d histochemistry staining, NOS and NO assay kit, respectively. It was found that
      formalin test significantly up-regulated NOS expression and activity and NO
      production in the laminae I-II of the dorsal horn and the grey matter around the
      central canal in the lumbar spinal cord at 1 h after the formalin test. Selective
      inhibition of glia metabolism with intrathecal administration of FC (1 nmol)
      significantly inhibited the up-regulation in NOS expression and activity and NO
      production normally induced by the formalin test, which was represented with
      decreases in the number and density of the NADPH-d positive cells in the dorsal
      horn and grey matter around the central canal, and decrease in density of NADPH-d
      positive neuropil in the dorsal horn in formalin + FC group compared with
      formalin group. The results suggested that glia may be involved in the NO
      mediated nociceptive transmission in the spinal cord.

PMID- 18629639
TI  - Body mass index and the efficacy of acid-mediating agents for GERD.
AB  - In studies of the association between obesity and gastroesophageal reflux, one
      subject that has received very little attention is the effect excess body mass
      may have on the effectiveness of acid-mediating agents. The lack of systematic
      research may reflect the perceived high clinical efficacy of drugs like proton
      pump inhibitors. Both proton pump inhibitors and histamine type 2 receptor
      antagonists have low rates of significant adverse events; if there are
      differences in the side effect profiles based on BMI, it is unlikely such
      associations would be detected. Also, while the metabolism of many drugs can be
      affected by body mass, it is not clear that such a relationship exists with acid
      mediating agents. Nevertheless, there is evidence that body mass index may indeed
      be associated with the efficacy of proton pump inhibitors and histamine type 2
      receptor antagonists. This review will examine that evidence and consider some of
      the possible pharmacokinetic effects that might relate to body mass index.

PMID- 18629640
TI  - Protective effect of morin on dimethylnitrosamine-induced hepatic fibrosis in
      rats.
AB  - Morin, a plant-derived flavonoid, has been reported to exhibit a wide range of
      pharmacological properties. In this study, we investigated the protective effect
      of morin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Oral
      administration of morin remarkably prevented weight loss in the body and liver
      from DMN and inhibited the elevation of serum alanine transaminase (ALT),
      aspartate transaminase (AST), and total bilirubin levels. For the evaluation of
      hepatic fibrosis-related factors, we investigated expressions of collagen type I,
      transforming growth factor beta(1) (TGF-beta(1)), and alpha-smooth muscle actin
      (alpha-SMA) in mRNA and protein levels. We observed that morin significantly
      reduced the expression of collagen type I, TGF-beta(1), and alpha-SMA on hepatic
      fibrosis induced by DMN. Taken together, this study demonstrated that morin
      showed hepatoprotective and antifibrogenic effects against DMN-induced hepatic
      injury. This suggests that morin may be useful in preventing the development of
      hepatic fibrosis and cirrhosis.

PMID- 18629641
TI  - Living donor liver transplantation for hepatocellular carcinoma: defining
      criteria to extend indications.

PMID- 18629642
TI  - Central nervous system plus autonomic nervous system disorders responsible for
      gastrointestinal and pancreatobiliary diseases.
AB  - Clinical digestive disorders depend on the non-adequate coupling of functioning
      of the gastrointestinal tract with that of its affluent systems, namely, the
      pancreatic exocrine and the hepato-biliary secretions. The secretion of
      gastrointestinal hormones is monitored by the peripheral autonomic nervous
      system. However, the latter is regulated by the central nervous system (CNS)
      circuitry localized at the medullary pontine segment of the CNS. In turn, both
      parasympathetic and adrenergic medullary circuitries are regulated by the pontine
      A5 noradrenergic (NA) and the dorsal raphe serotonergic nuclei, respectively. DR
      5HT is positively correlated with the C1-Ad medullary nuclei (responsible for
      adrenal gland secretion), whereas the MR-5HT nucleus is positively correlated
      with the A5-NA pontomedullary nucleus. The latter is responsible for neural
      sympathetic activity (sympathetic nerves). Both types of sympathetic activities
      maintain an alternation with the peripheral parasympathetic branch, which is
      positively correlated with the enterochromaffin cells that secrete serotonin.
      Serotonin displays hormonal antagonism to the circulating catecholamines.

PMID- 18629643
TI  - Clinical characteristics of patients with hepatitis C virus-related chronic liver
      disease seropositive for anticentromere antibody.
AB  - The association between anticentromere antibody (ACA) and hepatitis C virus (HCV)
      infection remains unclear. We subjected eight patients with HCV-related chronic
      liver disease (CLD) seropositive for ACA to a battery of clinical and laboratory
      tests. The patient cohort was dominated by females, and four of the eight (50%)
      patients had a concomitant autoimmune disease. All of the patients had high
      titers of ACA (>or=1:320). The histological activity index scores in chronic
      hepatitis C (CH-C) patients with ACA were significantly higher than those in CH-C
      patients without antinuclear antibody (ANA) (12.8 +/- 1.8 vs. 8.3 +/- 4.5, P =
      0.0372). The frequency of human leukocyte antigen (HLA) DR-8 in patients with HCV
      related CLD seropositive for ACA was significantly higher than that in patients
      with CH-C seronegative for ANA (71 vs. 18%, P = 0.0108). These findings suggest
      that ACA is induced by chronic HCV infection in association with HLA DR-8, and
      that CH-C patients with ACA exhibit more severe hepatic fibrosis and inflammation
      than CH-C patients without ANA.

PMID- 18629638
TI  - Cellular stress response: a novel target for chemoprevention and nutritional
      neuroprotection in aging, neurodegenerative disorders and longevity.
AB  - The predominant molecular symptom of aging is the accumulation of altered gene
      products. Moreover, several conditions including protein, lipid or glucose
      oxidation disrupt redox homeostasis and lead to accumulation of unfolded or
      misfolded proteins in the aging brain. Alzheimer's and Parkinson's diseases or
      Friedreich ataxia are neurological diseases sharing, as a common denominator,
      production of abnormal proteins, mitochondrial dysfunction and oxidative stress,
      which contribute to the pathogenesis of these so called "protein conformational
      diseases". The central nervous system has evolved the conserved mechanism of
      unfolded protein response to cope with the accumulation of misfolded proteins. As
      one of the main intracellular redox systems involved in neuroprotection, the
      vitagene system is emerging as a neurohormetic potential target for novel
      cytoprotective interventions. Vitagenes encode for cytoprotective heat shock
      proteins (Hsp) Hsp70 and heme oxygenase-1, as well as thioredoxin reductase and
      sirtuins. Nutritional studies show that ageing in animals can be significantly
      influenced by dietary restriction. Thus, the impact of dietary factors on health
      and longevity is an increasingly appreciated area of research. Reducing energy
      intake by controlled caloric restriction or intermittent fasting increases
      lifespan and protects various tissues against disease. Genetics has revealed that
      ageing may be controlled by changes in intracellular NAD/NADH ratio regulating
      sirtuin, a group of proteins linked to aging, metabolism and stress tolerance in
      several organisms. Recent findings suggest that several phytochemicals exhibit
      biphasic dose responses on cells with low doses activating signaling pathways
      that result in increased expression of vitagenes encoding survival proteins, as
      in the case of the Keap1/Nrf2/ARE pathway activated by curcumin and NAD/NADH
      sirtuin-1 activated by resveratrol. Consistently, the neuroprotective roles of
      dietary antioxidants including curcumin, acetyl-L-carnitine and carnosine have
      been demonstrated through the activation of these redox-sensitive intracellular
      pathways. Although the notion that stress proteins are neuroprotective is broadly
      accepted, still much work needs to be done in order to associate neuroprotection
      with specific pattern of stress responses. In this review the importance of
      vitagenes in the cellular stress response and the potential use of dietary
      antioxidants in the prevention and treatment of neurodegenerative disorders is
      discussed.

PMID- 18629644
TI  - Inhibitory effects of short-chain fatty acids on matrix metalloproteinase
      secretion from human colonic subepithelial myofibroblasts.
AB  - BACKGROUND AND AIMS: Short-chain fatty acids (SCFAs), such as acetate, propionate
      and butyrate, are the major by-product of bacterial fermentation of dietary fiber
      in the colon. In this report, we investigated how SCFAs modulate matrix
      metalloproteinase (MMP) secretion from human colonic subepithelial myofibroblasts
      (SEMFs). MATERIALS AND METHODS: SEMFs were identified by expression of alpha
      smooth muscle actin and vimentin. Cytokine-induced MMP-1 and MMP-3 levels were
      determined by enzyme-linked immunosorbent assay. Cytokine-induced MMP mRNA
      expression was analyzed by RT-PCR and real-time PCR methods. RESULTS: Acetate had
      no effect on MMP secretion. Propionate and butyrate significantly attenuated IL-1
      beta- and TNF-alpha-induced MMP-1 and MMP-3 secretion. Similar responses were
      also observed at the mRNA levels. Propionate and butyrate did not modulate IL-1
      beta- and TNF-alpha-induced activation of mitogen-activated protein kinases
      (MAPKs), which play a crucial role in MMP induction. Trichostatin A, a histone
      deacetylase inhibitor, reduced IL-1 beta-induced MMP-1 and MMP-3 mRNA expression,
      and suppressed TNF-alpha-induced MMP-3 mRNA expression. CONCLUSION: SCFAs play an
      anti-inflammatory role through suppression of MMP secretion in the colon.
      Inhibitory effects of SCFAs on MMP secretion might be associated with their
      action of histone hyperacetylation.

PMID- 18629645
TI  - RDW can be a useful additional marker in diagnosing Crohn's disease and
      ulcerative colitis.

PMID- 18629646
TI  - A DSP based multi-frequency 3D electrical impedance tomography system.
AB  - This paper describes the design of a multi-frequency Electrical impedance
      tomography (EIT) system, which provides a flexible mechanism for addressing up to
      48 electrodes for imaging conductivity and permittivity distributions. A waveform
      generator based on a digital signal processor is used to produce sinusoidal
      waveforms with the ability to select frequencies in the range of 0.1-125 kHz. A
      software based phase-sensitive demodulation technique is used to extract
      amplitudes and phases from the raw measurements. Signal averaging and automatic
      gain control are also implemented in voltage and phase measurements. System
      performance was validated using a Cardiff-Cole Phantom and a saline filled
      cylindrical tank. The signal-to-noise ratio (SNR) using saline tank was greater
      than 60 dB and the maximum reciprocity error less than 4% for most frequencies.
      The common-mode rejection ratio (CMRR) was nearly 60 dB at 50 kHz. Image
      reconstruction performance was assessed using data acquired through a range of
      frequencies. This EIT system offers image reconstruction of both conductivity and
      permittivity distributions in three dimensions. The imaging results are presented
      in time difference and frequency difference imaging.

PMID- 18629648
TI  - A parametric model for studies of flow in arterial bifurcations.
AB  - Regional differences in hemodynamic loads on arterial walls have been associated
      with localized vascular disease such as atherosclerosis and cerebral aneurysms.
      Due to their intrinsic geometric relevance, three-dimensional (3D)
      reconstructions of arterial segments are frequently used in hemodynamic studies
      of these diseases. However, it is not possible to use them to systematically vary
      geometric features for parametric studies. Idealized vascular models are
      inherently suited for parametric studies, but are limited by their tendency to
      oversimplify the vessel geometry. In this work, a hierarchy of three parametric
      bifurcation models is introduced. The models are relatively simple, yet capture
      all geometric features identified as common to cerebral bifurcations in the
      complex transition from parent to daughter branches. While these models were
      initially designed for parametric studies, we also evaluate the possibility of
      using them for 3D reconstruction of cerebral arteries, with the future goal of
      improving reconstruction of poor quality clinical data. The lumen surface and
      vessel hemodynamics are compared between two reconstructed cerebral bifurcations
      and matched parametric models. Good agreement is found. The average and maximum
      geometric differences are less than 3.1 and 10%, respectively for all three
      parametric models. The maximum difference in wall shear stress is less than 8%
      for the most complex parametric model.

PMID- 18629647
TI  - Post-treatment hemodynamics of a basilar aneurysm and bifurcation.
AB  - To investigate whether or not a successful aneurysm treatment procedure can
      subject a parent artery to harmful hemodynamic stresses, computational fluid
      dynamics simulations are performed on a patient-specific basilar aneurysm and
      bifurcation before and after a virtual endovascular treatment. Prior to
      treatment, the aneurysm at systole is filled with a periodic train of vortex
      tubes, which form at the aneurysm neck and advect upwards into the dome.
      Following the treatment procedure however, the motion of the vortex train is
      inhibited by the aneurysm filling material, which confines the vortex tubes to
      the region beneath the aneurysm neck. Analysis of the post-treatment flow field
      indicates that the impingement of the basilar artery flow upon the treated
      aneurysm neck and the close proximity of a vortex tube to the parent artery wall
      increase the maximum wall shear stresses to values approximately equal to 50 Pa
      at systole. Calculation of the time-averaged wall shear stresses indicates that
      there is a 1.4 x 10(-7) m(2) area on the parent artery exposed to wall shear
      stresses greater than 37.9 Pa, a value shown by Fry [Circ. Res. 22(2):165-197,
      1968] to cause severe damage to the endothelial cells that line the artery wall.
      The results of this study demonstrate that it is possible for a treatment
      procedure, which successfully isolates the aneurysm from the circulation and
      leaves no aneurysm neck remnant, to elevate the hemodynamic stresses to levels
      that are injurious to the artery wall.

PMID- 18629649
TI  - Out standing in our field.

PMID- 18629650
TI  - Neighborhood effects on an individual's health using neighborhood measurements
      developed by factor analysis and cluster analysis.
AB  - This study suggests a multivariate-structural approach combining factor analysis
      and cluster analysis that could be used to examine neighborhood effects on an
      individual's health. Data were from the Taiwan Social Change Survey conducted in
      1990, 1995, and 2000. In total, 5,784 women and men aged over 20 years living in
      428 neighborhoods were interviewed. Participants' addresses were geocoded with
      census data for measuring neighborhood-level characteristics. The factor analysis
      was applied to identify neighborhood dimensions, which were used as entities in
      the cluster analysis to generate a neighborhood typology. The factor analysis
      generated three neighborhood dimensions: neighborhood education, age structure,
      and neighborhood family structure and employment. The cluster analysis generated
      six types of neighborhoods with combinations of the three neighborhood
      dimensions. Multilevel binomial regression models were used to assess the effects
      of neighborhoods on an individual's health. The results showed that the biggest
      health differences were between two neighborhood types: (1) the highest
      concentration of inhabitants younger than 15 years, a moderate education level,
      and a moderate level of single-parent families and (2) the highest educational
      level, a median level of single-parent families, and a median level of elderly
      concentrations. Individuals living in the first type had significantly higher
      chances of having functional limitations and poor self-rated health than the
      individuals in the second neighborhood type. Our study suggests that the
      multivariate-structural approach improves neighborhood measurements by addressing
      neighborhood diversity and examining how an individual's health varies in
      different neighborhood contexts.

PMID- 18629651
TI  - Ventricular septal defect after percutaneous coronary intervention in acute
      myocardial infarction: a clinical study of two cases.

PMID- 18629652
TI  - When drug companies select what they want to publish patients are denied relevant
      therapeutic information.

PMID- 18629653
TI  - Herpetic leg paralysis and abdominal ileus in a patient with idiopathic
      myelofibrosis.

PMID- 18629654
TI  - Quantitative assessment of neuronal differentiation in three-dimensional collagen
      gels using enhanced green fluorescence protein expressing PC12 pheochromocytoma
      cells.
AB  - There is a paucity of quantitative methods for evaluating the morphological
      differentiation of neuronal cells in a three-dimensional (3-D) system to assist
      in quality control of neural tissue engineering constructs for use in reparative
      medicine. Neuronal cells tend to aggregate in the 3-D scaffolds, hindering the
      application of two-dimensional (2-D) morphological methods to quantitate neuronal
      differentiation. To address this problem, we developed a stable transfectant
      green fluorescence protein (GFP)-PC12 neuronal cell model, in which the
      differentiation process in 3-D can be monitored with high sensitivity by
      fluorescence microscopy. Under 2-D conditions, the green cells showed collagen
      adherence, round morphology, proliferation properties, expression of the nerve
      growth factor (NGF) receptors TrkA and p75(NTR), stimulation of extracellular
      signal-regulated kinase phosphorylation by NGF and were able to differentiate in
      a dose-dependent manner upon NGF treatment, like wild-type (wt)-PC12 cells. When
      grown within 3-D collagen gels, upon NGF treatment, the GFP-PC12 cells
      differentiated, expressing long neurite outgrowths. We describe here a new
      validated method to measure NGF-induced differentiation in 3-D. Having properties
      similar to those of wt-PC12 and an ability to grow and differentiate in 3-D
      structures, these highly visualized GFP-expressing PC12 cells may serve as an
      ideal model for investigating various aspects of differentiation to serve in
      neural engineering.

PMID- 18629655
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal peptide (VIP) regulate murine neural progenitor cell survival,
      proliferation, and differentiation.
AB  - Neural stem/progenitor cells (NPC) have gained wide interest over the last decade
      from their therapeutic potential, either through transplantation or endogenous
      replacement, after central nervous system (CNS) disease and damage. Whereas
      several growth factors and cytokines have been shown to promote NPC survival,
      proliferation, or differentiation, the identification of other regulators will
      provide much needed options for NPC self-renewal or lineage development. Although
      previous studies have shown that pituitary adenylate cyclase-activating
      polypeptide (PACAP)/vasoactive intestinal peptide (VIP) can regulate
      stem/progenitor cells, the responses appeared variable. To examine the direct
      roles of these peptides in NPCs, postnatal mouse NPC cultures were withdrawn from
      epidermal growth factor (EGF) and fibroblastic growth factor (FGF) and maintained
      under serum-free conditions in the presence or absence of PACAP27, PACAP38, or
      VIP. The NPCs expressed the PAC1(short)null receptor isoform, and the activation
      of these receptors decreased progenitor cell apoptosis more than 80% from TUNEL
      assays and facilitated proliferation more than fivefold from bromodeoxyuridine
      (BrdU) analyses. To evaluate cellular differentiation, replicate control and
      peptide-treated cultures were examined for cell fate marker protein and
      transcript expression. In contrast with previous work, PACAP peptides
      downregulated NPC differentiation, which appeared consistent with the
      proliferation status of the treated cells. Accordingly, these results demonstrate
      that PACAP signaling is trophic and can maintain NPCs in a multipotent state.
      With these attributes, PACAP may be able to promote endogenous NPC self-renewal
      in the adult CNS, which may be important for endogenous self-repair in disease
      and ageing processes.

PMID- 18629656
TI  - Clinicopathological features of growth hormone-producing pituitary adenomas:
      difference among various types defined by cytokeratin distribution pattern
      including a transitional form.
AB  - Pituitary adenomas producing almost exclusively growth hormones (GH) have been
      ultrastructurally classified into two distinct types: densely granulated
      somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body
      (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is
      a hallmark of SG adenomas. Under light microscope, FB could be identified by CK
      immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern
      for cells without FB. However, it has been noted that numerous adenomas contain
      mixed populations of the two patterns. To clarify clinicopathological
      characteristics of the adenomas with mixed populations ("intermediate type"
      adenomas) and to confirm clinicopathological differences between strictly defined
      DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas.
      Having segregated "intermediate-type" adenomas (26 cases), we found significant
      differences between typical DG-type (47 cases) and SG-type adenomas (31 cases);
      SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas
      (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's
      classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha
      subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of
      "intermediate-type" adenomas were identical to those of DG-type adenomas. These
      findings confirm that SG-type adenoma is a distinct section of GH cell adenomas
      with special properties and biological behavior, and suggest that intermediate
      phenotype adenomas are enrolled in DG-type adenomas. Special properties and
      biological behavior of SG-type adenomas may appear after the majority of tumor
      cells possess a fully developed fibrous body.

PMID- 18629657
TI  - From gene-scale to genome-scale phylogenetics: the data flood in, but the
      challenges remain.
AB  - An important goal of phylogenetics is to be able to consistently and accurately
      reconstruct the historical patterns of cladogenesis among major organismic
      groups. Gene-scale phylogenetics is insufficient to attain this goal owing to the
      presence of poor resolution and incongruence in single--and few--gene
      phylogenies. The increasing availability of genome-scale amounts of data promises
      to overcome the insufficiency of gene-scale phylogenetics and uncover the
      genealogical tapestry uniting all living organisms with unprecedented accuracy.
      Here, we argue that a vast increase in data size alone--although necessary--may
      not be sufficient to achieve the desired accuracy for three reasons: (i) the
      existence of short stems in the tree of life, (ii) the saturation of phylogenetic
      signal in molecular sequences, and (iii) the effect of systematic error on
      phylogenetic inference. Devising strategies to ameliorate the effect of such
      challenges on sequence evolution will be critical to the success of current
      efforts to reconstruct the tree of life.

PMID- 18629658
TI  - Phylogenomic analysis by chromosome sorting and painting.
AB  - Chromosome sorting by flow cytometry is the principle source of chromosome
      specific DNA not only for chromosome painting, but also for many other types of
      genomic analysis such as library construction, discovery and isolation of genes,
      chromosome specific direct DNA selection, and array painting. Chromosome sorting
      coupled with chromosome painting is a rapid method for global phylogenomic
      comparisons. These two techniques have made notable contributions to our
      knowledge of the evolution of the mammalian genome. The flow sorting of multiple
      species allows reciprocal painting and permits the delineation of subchromosomal
      homology and the definition of chromosomal breakpoints. Chromosomes are valuable
      phylogenetic makers because rearrangements that become fixed at the species level
      are considered rare events and apparently tightly bound to the speciation
      process. This chapter covers the preparation of a single chromosome suspension
      from cell cultures, bivariate chromosome flow sorting, preparation of chromosome
      paints by degenerate oligonucleotide primed-PCR and the fluorescence in-situ
      hybridization and detection of whole chromosome specific probes.

PMID- 18629659
TI  - FISH for mapping single copy genes.
AB  - During the past two decades fluorescent in-situ hybridization (FISH) has become a
      standard technique to directly localize, orient, and order genes in the genomes
      of a wide range of species. Despite the availability of a variety of probes,
      probe labeling and signal-detection systems, and advanced image analysis
      software, the core procedures used to carry out FISH remain the same. A detailed
      overview of these procedures, including target preparation (metaphase/interphase
      chromosomes and DNA fibers), probe labeling, in-situ hybridization, signal
      detection, and imaging, is here provided in a stepwise manner.

PMID- 18629660
TI  - Construction of radiation hybrid panels.
AB  - Whole-genome radiation hybrid (RH) mapping has proven to be a powerful tool for
      mapping genes and comparing genome architecture. We describe a protocol for
      constructing RH panels by rescuing irradiated fibroblast donor cells of any
      mammalian species by polyethylene glycol fusion to a thymidine kinase-deficient
      hamster cell line. Characterization and expansion of a panel of 90-100 cell lines
      can be used to map virtually any PCR-based marker that can be distinguished from
      the recipient hamster genome. The described procedure has been used successfully
      to create RH panels from diverse mammalian species such as macaques, elephants,
      alpacas, and armadillos, and may be applicable to nonmammalian vertebrates as
      well.

PMID- 18629661
TI  - Survey sequencing and radiation hybrid mapping to construct comparative maps.
AB  - Radiation hybrid (RH) mapping has become one of the most well-established
      techniques for economically and efficiently navigating genomes of interest. The
      success of the technique relies on random chromosome breakage of a target genome,
      which is then captured by recipient cells missing a preselected marker. Selection
      for hybrid cells that have DNA fragments bearing the marker of choice, plus a
      random set of DNA fragments from the initial irradiation, generates a set of cell
      lines that recapitulates the genome of the target organism several-fold. Markers
      or genes of interest are analyzed by PCR using DNA isolated from each cell line.
      Statistical tools are applied to determine both the linear order of markers on
      each chromosome, and the confidence of each placement. The resolution of the
      resulting map relies on many factors, most notably the degree of breakage from
      the initial radiation as well as the number of hybrid clones and mean retention
      value.A high-resolution RH map of a genome derived from low pass or survey
      sequencing (coverage from 1 to 2 times) can provide essentially the same
      comparative data on gene order that is derived from high-coverage (greater than
      x7) genome sequencing. When combined with fluorescence in situ hybridization, RH
      maps are complete and ordered blueprints for each chromosome. They give
      information about the relative order and spacing of genes and markers, and allow
      investigators to move between target and reference genomes, such as those of
      mouse or human, with ease although the approach is not limited to mammal genomes.

PMID- 18629662
TI  - Construction of high-resolution comparative maps in mammals using BAC-end
      sequences.
AB  - Whole-genome bacterial artificial chromosome (BAC) libraries for approximately 40
      representative species of mammals provide unique resources for the construction
      of high-resolution ordered genomic maps, the development of species genetics, and
      multispecies genome comparisons. Herein we describe procedures to construct high
      quality radiation hybrid comparative maps using BAC-end sequences (BESs). This
      approach has been applied to the construction of approximately 1 Mbp resolution
      porcine-human and cattle-human comparative maps. High-resolution ordered
      comparative maps built with BESs and whole-genome sequences have been shown to be
      an invaluable resource for the analysis of mammalian chromosome evolution, and as
      a backbone for the assembly of whole-genome shotgun sequences.

PMID- 18629663
TI  - Amniote phylogenomics: testing evolutionary hypotheses with BAC library scanning
      and targeted clone analysis of large-scale DNA sequences from reptiles.
AB  - Phylogenomics research integrating established principles of systematic biology
      and taking advantage of the wealth of DNA sequences being generated by genome
      science holds promise for answering long-standing evolutionary questions with
      orders of magnitude more primary data than in the past. Although it is
      unrealistic to expect whole-genome initiatives to proceed rapidly for
      commercially unimportant species such as reptiles, practical approaches utilizing
      genomic libraries of large-insert clones pave the way for a phylogenomics of
      species that are nevertheless essential for testing evolutionary hypotheses
      within a phylogenetic framework. This chapter reviews the case for adopting
      genome-enabled approaches to evolutionary studies and outlines a program for
      using bacterial artificial chromosome (BAC) libraries or plasmid libraries as a
      basis for completing "genome scans" of reptiles. We have used BACs to close a
      critical gap in the genome database for Reptilia, the sister group of mammals,
      and present the methodological approaches taken to achieve this as a guideline
      for designing similar comparative studies. In addition, we provide a detailed
      step-by-step protocol for BAC-library screening and shotgun sequencing of
      specific clones containing target genes of evolutionary interest. Taken together,
      the genome scanning and shotgun sequencing techniques offer complementary
      diagnostic potential and can substantially increase the scale and power of
      analyses aimed at testing evolutionary hypotheses for nonmodel species.

PMID- 18629664
TI  - Comparative physical mapping: Universal overgo hybridization probe design and BAC
      library hybridization.
AB  - Comparative genomics is a powerful approach for inferring the history and
      function of genomic sequence. The generation of bacterial artificial chromosome
      (BAC)-based physical maps is a proven method for the targeted comparative genomic
      analysis of genes or regions of interest. 'Universal' overgo hybridization probes
      can be used for the efficient construction of BAC-based physical maps of
      orthologous chromosome segments from multiple species in parallel. 'Universal'
      overgo hybridization probes can therefore facilitate the assembly of deep and
      diverse collections of experimental and computational comparative genomic
      resources corresponding to specific segments of the genome. The design of
      'universal' overgo probes is dependent on the presence of sequences that are
      highly conserved within a group of species. Such conserved sequences can be
      readily identified using local-or whole-genome interspecies sequence alignments.
      Once 'universal' overgo hybridization probes are designed, simple and uniform
      labeling and hybridization conditions can be carried out to exploit the utility
      of these probes for targeted comparative physical mapping.

PMID- 18629665
TI  - Phylogenomic resources at the UCSC Genome Browser.
AB  - The UC Santa Cruz Genome Browser provides a number of resources that can be used
      for phylogenomic studies, including (1) whole-genome sequence data from a number
      of vertebrate species, (2) pairwise alignments of the human genome sequence to a
      number of other vertebrate genome, (3) a simultaneous alignment of 17 vertebrate
      genomes (most of them incompletely sequenced) that covers all of the human
      sequence, (4) several independent sets of multiple alignments covering 1% of the
      human genome (ENCODE regions), (5) extensive sequence annotation for interpreting
      those sequences and alignments, and (6) sequence, alignments, and annotations
      from certain other species, including an alignment of nine insect genomes. We
      illustrate the use of these resources in the context of assigning rare genomic
      changes to the branch of the phylogenetic tree where they appear to have
      occurred, or of looking for evidence supporting a particular possible tree
      topology. Sample source code for performing such studies is available.

PMID- 18629666
TI  - Computational tools for the analysis of rearrangements in mammalian genomes.
AB  - The chromosomes of mammalian genomes exhibit reasonably high levels of similarity
      that can be used to study small-scale sequence variations. A different approach
      is to study the evolutionary history of rearrangements in entire genomes based on
      the analysis of gene or segment orders. We describe three computational tools
      (GRIMM-Synteny, GRIMM, and MGR) that can be used separately or in succession to
      contrast different organisms at the genome-level to exploit large-scale
      rearrangements as a phylogenetic character.

PMID- 18629667
TI  - Computational reconstruction of ancestral DNA sequences.
AB  - This chapter introduces the problem of ancestral sequence reconstruction: given a
      set of extant orthologous DNA genomic sequences (or even whole-genomes), together
      with a phylogenetic tree relating these sequences, predict the DNA sequence of
      all ancestral species in the tree. Blanchette et al. (1) have shown that for
      certain sets of species (in particular, for eutherian mammals), very accurate
      reconstruction can be obtained. We explain the main steps involved in this
      process, including multiple sequence alignment, insertion and deletion inference,
      substitution inference, and gene arrangement inference. We also describe a
      simulation-based procedure to assess the accuracy of the reconstructed sequences.
      The whole reconstruction process is illustrated using a set of mammalian
      sequences from the CFTR region.

PMID- 18629668
TI  - Sequencing and phylogenomic analysis of whole mitochondrial genomes of animals.
AB  - Mitochondrial genomes (mtDNA) of animals are circular molecules of relatively
      small size, compactly organized, and generally encoding genes for 2 rRNAs, 22
      tRNAs, and 13 proteins that are required for mitochondrial function. Methods of
      mtDNA isolation take advantage of its physical localization apart from the
      nuclear genome (centrifugation at low speed efficiently separates mitochondria
      from nuclei) and of its structure (alkaline lysis differentially precipitates
      linear nuclear DNA, but not circular mtDNA). Furthermore, the recent development
      of robust long-PCR techniques has boosted high-throughput determination of
      complete sequences of animal mtDNAs. The exponentially growing number of complete
      animal mitochondrial genomes deposited in GenBank allows a phylogenomic approach
      to disentangle phylogenetic relationships among main animal phyla, and provides
      extensive new data to gain insights on the molecular mechanisms underlying genome
      evolution.

PMID- 18629669
TI  - Retroposons: genetic footprints on the evolutionary paths of life.
AB  - Retroposons such as short interspersed elements (SINEs) and long interspersed
      elements are abundant transposable elements in eukaryote genomes. Recent large
      scale comparative genome analyses have revealed that retroposons are a major
      component of genomes, wherein they provide structural diversity between species
      and uniqueness to each species. SINEs have been used as powerful markers in
      phylogenetic analyses of various species. This approach, which has been termed
      the SINE insertion method, infers phylogenetic relationships based on the
      presence/absence of SINEs among lineages. However, the method is not yet used
      extensively among biologists, especially molecular phylogenetists, because it is
      based on an understanding of the molecular mechanisms of retroposition, which may
      be unfamiliar to many researchers. Moreover, the method may require a large
      amount of bench work to characterize a new SINE family and to screen genomic
      libraries of the species of interest. In this chapter, we present the basic
      theory and detailed technical steps involved in a SINE insertion analysis.
      Furthermore, we explain the isolation and characterization of a new SINE family
      from the genome of a species of interest using as an example a known SINE family
      in mammals.

PMID- 18629670
TI  - LINE-1 elements: analysis by fluorescence in-situ hybridization and nucleotide
      sequences.
AB  - Long-interspersed nuclear element-1 (LINE-1) is a non-terminal repeat transposon
      that constitutes a major component of the mammalian genome. LINE-1 has a dynamic
      evolutionary history characterized by the rise, fall, and replacement of
      subfamilies. The distribution of LINE-1 elements can be viewed from a chromosomal
      perspective using fluorescence in-situ hybridization (FISH), as well as at the
      sequence level. We have designed LINE-1 primers from regions conserved among
      mouse, rat, rabbit, and human L1, which were able to amplify part of ORF2 from
      all eutherian (placental) mammals tested thus far. The product generated can be
      used as a FISH painting probe to examine the genomic distribution of L1 in
      different species. It can also be cloned and sequenced for phylogenetic analysis.
      Although FISH patterns resulting from LINE-1 chromosome painting and
      bioinformatic analyses have shown that this element accumulates in AT-rich
      regions of the genomes of mouse and human, our PCR amplified LINE-1 probe
      suggests that this is not a universal phenomenon, and that the patterns displayed
      in laurasiatherian, afrotherian and xenarthran species are less prominent. The
      "banding" like distribution of LINE-1 observed in human and mouse, therefore,
      appears to reflect aspects of genome architecture unique to Euarchontoglires
      (Supraprimates), the superordinal clade to which they belong. By sequencing the
      cloned amplicons used for FISH experiments and supplementing these with L1
      sequences obtained from public databases, analysis by parsimony, distance-based,
      maximum likelihood, and "hierarchical Bayesian" or "marginal likelihood" methods
      provides a powerful adjunct to the FISH data. Using this approach, relatively
      intact LINE-1 from most placental orders tend to reflect accepted eutherian
      evolutionary relationships. This suggests that there were often only closely
      related copies active near branch points in the tree, that inactive copies tended
      to become extinct quite readily, and that for many orders recently active copies
      belong to a single lineage of this LINE.

PMID- 18629671
TI  - Identification of cryptic sex chromosomes and isolation of X- and Y-borne genes.
AB  - Comparative molecular cytogenetics provides a powerful tool for deciphering the
      evolutionary history of vertebrate sex chromosomes. We have adapted cell culture
      and molecular cytogenetic techniques to study the sex chromosomes of many exotic
      mammals, birds, and reptiles. Here we describe differential chromosome banding
      and staining techniques that distinguish sex chromosomes in species with no
      morphologically distinct XY or ZW chromosome pairs. We describe a method to
      isolate, identify, and map genomic BAC clones from the Y chromosome, and we also
      identify strategies for isolating candidate sex chromosome genes.

PMID- 18629672
TI  - Localization of transient receptor potential vanilloid (TRPV) in the human
      larynx.
AB  - CONCLUSION: Transient receptor potential vanilloid (TRPV) 1, 2, 3, and 4 were
      expressed in the human larynx, which may act as laryngeal nociceptors perceiving
      luminal noxious stimuli, play an important role in thermal sensation and osmotic
      sensation, and are also related to some pathological conditions and prevention of
      aspiration. OBJECTIVE: Expression of TRPV1, 2, 3, and 4 in the human larynx was
      analyzed. MATERIALS AND METHODS: Specimens of human epiglottic epithelium
      obtained from six patients were used in this study. The localization of TRPV1, 2,
      3, and 4 in the laryngeal epithelium was investigated by immunohistochemistry.
      RESULTS: Immunohistochemical study revealed the presence of TRPV1, 2, 3, and 4 in
      the laryngeal epithelial cells. Chemoradiotherapy may reduce the expression of
      TRPV1, 2, 3, and 4, which might be a result of the mucositis and neuropathy in
      laryngeal epithelium.

PMID- 18629673
TI  - Reliance on schemas in source memory: age differences and similarity of schemas.
AB  - The present study has examined the effects of source-schema-consistency,
      schematic distinctiveness and encoding time of schematic information on source
      memory of younger and older adults. Participants were administered a source
      memory test, in which two sources presented statements that were congruent with,
      incongruent with or irrelevant to sources' professions. Professions of sources
      were schematically similar or distinct, and they were revealed before or after
      the presentation of items. The results yielded that revelation of profession
      information before presentation of items enhanced source memory for incongruent
      items. Aging was associated with a general decrease in source monitoring
      processes. Participants who were assigned to similar-source condition and had
      their schemas activated before learning phase had higher source monitoring
      scores. Results are discussed in relation to source monitoring framework and
      aging of memory.

PMID- 18629674
TI  - The contribution of executive skills to reading comprehension.
AB  - Although word recognition deficits (WRD) are a known cause of reading
      comprehension deficits (RCD), other contributions to RCD, including executive
      function (EF), have not been fully explored. We examined the contribution of EF
      (working memory and planning), along with attention, decoding, fluency, and
      vocabulary to reading comprehension in 60 children (including 16 WRD and 10 RCD),
      ages 9-15 years. After controlling for commonly accepted contributors to reading
      comprehension (i.e., attention, decoding skills, fluency, and vocabulary), EF
      continued to make a significant contribution to reading comprehension but not to
      word recognition skills. These findings highlight the need for consideration of
      the role of EF in RCD.

PMID- 18629675
TI  - Spontaneous eruptive keloid-like cutaneous lesions in a renal transplant patient:
      a form of nephrogenic systemic fibrosis?
AB  - This is a case report of a 63-year-old man post renal transplant who developed
      eruptive keloids, many of which developed with no history of previous trauma.
      Reports of spontaneous keloids are rare in the literature, and given his history
      of renal failure, we have considered a connection with nephrogenic systemic
      fibrosis (NSF). With no history of prior keloid formation, the patient developed
      a large number of lesions with a wide distribution, which then subsequently
      healed without keloid formation. Additionally, the lesions stained positive for
      CD68 and factor XIIIa, both of which are correlated with the lesions of NSF.
      However, the patient did not present with the classic clinical presentation of
      NSF, had no history of exposure to gadolinium, and staining for CD34 was
      negative. In conclusion, NSF is a relatively new disease, the details of which
      have yet to be clearly established. This case may represent a variant of NSF.

PMID- 18629676
TI  - Th17 cells: a new paradigm for cutaneous inflammation.
AB  - Inflammatory processes of the skin have classically been segregated to either the
      cell-mediated, T-helper type 1 (Th1) or the humoral (Th2) branch of the immune
      system. The recent addition of Th17 cells, a novel T-helper cell named for its
      secretion of interleukin (IL)-17, to current thinking in autoimmunity has
      resulted in a significant paradigm shift in immunological thinking. Collectively,
      Th17 cytokines have been found to stimulate cutaneous immune reactions through an
      activation of a wide range of downstream inflammatory mediators and an induction
      of immune cell and keratinocyte proliferation as well as angiogenesis. Newly
      developed treatment modalities for neutralizing the Th17 branch of the immune
      system are proving to be valuable additions to the current therapeutic
      armamentarium. Here we describe a new schema for dermatologic T-cell-mediated
      immunity. We elucidate experiments confirming the presence of Th17 cells,
      followed by a discussion of their relevance to cutaneous inflammation and
      psoriasis.

PMID- 18629677
TI  - Paradoxical hypertrichosis and terminal hair change after intense pulsed light
      hair removal therapy.
AB  - BACKGROUND: Although complications such as blister formation, erosion, and post
      inflammatory hypo- and hyperpigmentation are well-known side effects of intense
      pulsed light (IPL) photoepilation, little is known about the paradoxical
      hypertrichosis after therapy. OBJECTIVE: To report the paradoxically increased
      hair density and coarseness after IPL photoepilation. METHODS: Within a period of
      23 months, a total of 991 hirsute female patients were treated with IPL for
      photoepilation. The IPL system used was the Vasculight-SR, a multifunctional
      laser and IPL system (Lumenis Inc., Santa Clara, CA, USA). The cut-off filters
      frequently used were 695, 755 and 645 nm. RESULTS: Paradoxical hypertrichosis and
      terminal hair change were detected after a few sessions of IPL therapy among 51
      out of 991 patients. Our serial digital photographs, schematic diagrams, and hair
      counts before and after treatment confirmed the patients' claims. The other more
      commonly seen complications were epidermal burning with blisters, erosion, and
      crust formation followed by post-inflammatory hypo- and/or hyperpigmentation.
      CONCLUSION: Paradoxical hypertrichosis and terminal hair change is a common
      complication of IPL photoepilation.

PMID- 18629678
TI  - Synthesis and antitubercular activity of a series of hydrazone and nitrovinyl
      analogs derived from heterocyclic aldehydes.
AB  - A series of hydrazone and 3-nitrovinyl analogs of indole-3-carboxaldehydes and
      related compounds were synthesized and screened for antitubercular activity
      against Mycobacterium tuberculosis H37R(V) in BACTEC 12B medium using the
      Microplate Alamar Blue Assay (MABA). Several compounds showed inhibitory activity
      against M. tuberculosis in primary screening assays at a concentration of 6.25
      microg/mL; subsequent dose-response studies indicated that the most active
      compounds, 3d, 3e & 8b, had IC(50) values of 5.96, 5.4 & 1.6 microg/mL,
      respectively. These compounds represent potential leads for the further
      development of novel antitubercular agents.

PMID- 18629679
TI  - Computational neural network analysis of the affinity of N-n-alkylnicotinium
      salts for the alpha4beta2* nicotinic acetylcholine receptor.
AB  - Based on an 85 molecule database, linear regression with different size datasets
      and an artificial neural network approach have been used to build mathematical
      relationships to fit experimentally obtained affinity values (K(i)) of a series
      of mono- and bis-quaternary ammonium salts from [(3)H]nicotine binding assays
      using rat striatal membrane preparations. The fitted results were then used to
      analyze the pattern among the experimental K(i) values of a set of N-n
      alkylnicotinium analogs with increasing n-alkyl chain length from 1 to 20
      carbons. The affinity of these N-n-alkylnicotinium compounds was shown to
      parabolically vary with increasing numbers of carbon atoms in the n-alkyl chain,
      with a local minimum for the C(4) (n-butyl) analogue. A decrease in K(i) value
      between C(12) and C(13) was also observed. The statistical results for the best
      neural network fit of the 85 experimental K(i) values are r(2) = 0.84, rmsd =
      0.39; r(cv)(2) = 0.68, and loormsd = 0.56. The generated neural network model
      with the 85 molecule training set may also be of value for future predictions of
      K(i) values for new virtual compounds, which can then be identified, subsequently
      synthesized, and tested experimentally.

PMID- 18629680
TI  - Synthesis and biological evaluation of some new N(4)-substituted isatin-3
      thiosemicarbazones.
AB  - A new series of 12 N(4)-substituted isatin-3-thiosemicarbazones 2a-l has been
      synthesized, characterized and screened for in vitro cytotoxic, phytotoxic and
      urease inhibitory effects. All the compounds proved to be active in the brine
      shrimp bioassay; 2a, 2b, 2d, 2f and 2h-l exhibited a high degree of cytotoxic
      activity (LD(50) = 1.10 x 10(- 5) M-3.10 x 10(- 5) M). In urease-inhibition
      assay, compounds 2a, 2b, 2e, 2f, 2h-j and 2l proved to be potent inhibitors
      displaying relatively much greater inhibition of the enzyme with IC(50) values
      ranging from 20.6 microM to 50.6 microM. Amongst these, 2a and 2f were found to
      be the most potent ones exhibiting pronounced inhibition with IC(50) value 20.6
      microM. All the synthetic compounds showed weak to moderate (10-40%)
      phytotoxicity at the highest tested concentration (500 microg/mL) indicating
      their usefulness as inhibitors of soil ureases.

PMID- 18629681
TI  - Rat liver mitochondrial carnitine palmitoyltransferase-I, hepatic carnitine, and
      malonyl-CoA: effect of starvation.
AB  - Hepatic mitochondrial fatty acid oxidation and ketogenesis increase during
      starvation. Carnitine palmitoyltransferase I (CPT-I) catalyses the rate
      controlling step in the overall pathway and retains its control over beta
      oxidation under fed, starved and diabetic conditions. To determine the factors
      contributing to the reported several-fold increase in fatty acid oxidation in
      perfused livers, we measured the V(max) and K(m) values for palmitoyl-CoA and
      carnitine, the K(i) (and IC(50)) values for malonyl-CoA in isolated liver
      mitochondria as well as the hepatic malonyl-CoA and carnitine contents in control
      and 48 h starved rats. Since CPT-I is localized in the mitochondrial outer
      membrane and in contact sites, the kinetic properties of CPT-I also was
      determined in these submitochondrial structures. After 48 h starvation, there is:
      (a) a significant increase in K(i) and decrease in hepatic malonyl-CoA content;
      (b) a decreased K(m) for palmitoyl-CoA; and (c) increased catalytic activity
      (V(max)) and CPT-I protein abundance that is significantly greater in contact
      sites compared with outer membranes. Based on these changes the estimated
      increase in mitochondrial fatty acid oxidation is significantly less than that
      observed in perfused liver. This suggests that CPT-I is regulated in vivo by
      additional mechanism(s) lost during mitochondrial isolation or/and that
      mitochondrial oxidation of peroxisomal beta-oxidation products contribute to the
      increased ketogenesis by bypassing CPT-I. Furthermore, the greater increase in
      CPT-I protein in contact sites as compared to outer membranes emphasizes the
      significance of contact sites in hepatic fatty acid oxidation.

PMID- 18629682
TI  - The effect of PPAR ligands to modulate glucose metabolism alters the
      incorporation of metabolic precursors into proteoglycans synthesized by human
      vascular smooth muscle cells.
AB  - PPAR ligands are important effectors of energy metabolism and can modify
      proteoglycan synthesis by vascular smooth muscle cells (VSMCs). Describing the
      cell biology of these important clinical agents is important for understanding
      their full clinical potential, including toxicity. Troglitazone (10 microM) and
      fenofibrate (30 microM) treatment of VSMCs reduces ((35)S)-sulphate incorporation
      into proteoglycans due to a reduction of glycosaminoglycan (GAG) chain length.
      Conversely, under physiological glucose conditions (5.5 mM), the same treatment
      increases ((3)H)-glucosamine incorporation into GAGs. This apparent paradox is
      the consequence of an increase in the intracellular ((3)H)-galactosamine specific
      activity from 48.2 +/- 3.2 microCi/ micromol to 90.7 +/- 11.0 microCi/ micromol
      (P < 0.001) and 57.1 +/- 2.6 microCi/ micromol (P < 0.05) when VSMCs were treated
      with troglitazone and fenofibrate, respectively. The increased specific activity
      observed with troglitazone (10 microM) treatment correlates with a two-fold
      increase in glucose consumption, while fenofibrate (50 microM) treatment showed a
      modest (14.6%) increase in glucose consumption. We conclude that the sole use of
      glucosamine precursors to assess GAG biosynthesis results in misleading
      conclusions when assessing the effect of PPAR ligands on VSMC proteoglycan
      biosynthesis.

PMID- 18629683
TI  - Ghrelin and orotic acid increased in subclinical mastitis.
AB  - Hormone ghrelin and orotic acid accelerate wound healing as well as controlling
      inflammation and immunity. We have, therefore, investigated the serum and milk
      levels of ghrelin and orotic acid in dairy cows with (n = 21) or without (n = 21)
      subclinical mastitis. Acylated and des-acylated ghrelin as well as orotic acid
      concentration were detected by using high performance liquid chromatography
      (HPLC). The results revealed that ghrelin level in milk and serum was
      significantly higher in dairy cows with subclinical mastitis than that of dairy
      cows without subclinical mastitis. This was also the case when the orotic acid
      concentrations in dairy cows with subclinical mastitis were compared with those
      dairy cows without subclinical mastitis. In conclusion, ghrelin and orotic acid
      occur in particularly high concentrations in subclinical mastitis, and might,
      therefore, be required in greater amounts for tissue repair and may be also used
      as a indicator for subclinical mastitis.

PMID- 18629684
TI  - Insulin resistance associated to obesity: the link TNF-alpha.
AB  - Adipose tissue secretes proteins which may influence insulin sensitivity. Among
      them, tumour necrosis factor (TNF)-alpha has been proposed as a link between
      obesity and insulin resistance because TNF-alpha is overexpressed in adipose
      tissue from obese animals and humans, and obese mice lacking either TNF-alpha or
      its receptor show protection against developing insulin resistance. The
      activation of proinflammatory pathways after exposure to TNF-alpha induces a
      state of insulin resistance in terms of glucose uptake in myocytes and adipocytes
      that impair insulin signalling at the level of the insulin receptor substrate
      (IRS) proteins. The mechanism found in brown adipocytes involves Ser
      phosphorylation of IRS-2 mediated by TNF-alpha activation of MAPKs. The Ser307
      residue in IRS-1 has been identified as a site for the inhibitory effects of TNF
      alpha in myotubes, with p38 mitogen-activated protein kinase (MAPK) and inhibitor
      kB kinase being involved in the phosphorylation of this residue. Moreover, up
      regulation of protein-tyrosine phosphatase (PTP)1B expression was recently found
      in cells and animals treated with TNF-alpha. PTP1B acts as a physiological
      negative regulator of insulin signalling by dephosphorylating the phosphotyrosine
      residues of the insulin receptor and IRS-1, and PTP1B expression is increased in
      peripheral tissues from obese and diabetic humans and rodents. Accordingly, down
      regulation of PTP1B activity by treatment with pharmacological agonists of
      nuclear receptors restores insulin sensitivity in the presence of TNF-alpha.
      Furthermore, mice and cells deficient in PTP1B are protected against insulin
      resistance induced by this cytokine. In conclusion, the absence or inhibition of
      PTP1B in insulin-target tissues could confer protection against insulin
      resistance induced by cytokines.

PMID- 18629685
TI  - Prostanoid function and cardiovascular disease.
AB  - Prostanoids, including prostaglandins (PGs) and thromboxanes (TXs) are
      synthesized from arachidonic acid by the combined action of cyclooxygenases
      (COXs) and PG and TX synthases. Finally after their synthesis, prostanoids are
      quickly released to the extracellular medium exerting their effects upon
      interaction with prostanoid receptors present in the neighbouring cells. These
      agents exert important actions in the cardiovascular system, modulating vascular
      homeostasis and participating in the pathogenesis of vascular diseases as
      thrombosis and atherosclerosis. Among prostanoids, Tromboxane (TX)A(2), a potent
      platelet activator and vasoconstrictor and prostacyclin (PGI2), a platelet
      inhibitor and vasodilator, are the most important in controlling vascular
      homeostasis. Although multiple studies using pharmacological inhibitors and
      genetically deficient mice have demonstrated the importance of prostanoid
      mediated actions on cardiovascular physiology, further analysis on the prostanoid
      mediated actions in the vascular system are required to better understand the
      benefits and risks for the use of COX inhibitors in cardiovascular diseases.

PMID- 18629686
TI  - Sleep-related dissociative disorder in a 6-year-old girl.
AB  - Sleep-related dissociative disorders are parasomnias that can emerge at any point
      during the sleep period and are associated with traumatic life experiences. No
      reports to date have described this parasomnia in a school-age child. This case
      report discusses presentation, diagnosis, and treatment of a 6-year-old girl with
      this diagnosis. Sleep-related dissociative disorder should be considered in young
      children who have experienced traumatic life events and who present with abnormal
      sleep patterns and bizarre behavior. Early identification and intensive
      psychotherapy can be efficacious for these children.

PMID- 18629687
TI  - Physiological-emotional reactivity to nightmare-related imagery in trauma-exposed
      persons with chronic nightmares.
AB  - Script-driven imagery was used to assess nightmare imagery-evoked physiological
      emotional reactivity (heart rate, skin conductance, facial electromyogram,
      subjective ratings) in trauma-exposed persons suffering from chronic nightmares.
      Goals were to determine the efficacy of nightmare imagery to evoke physiological
      emotional reactivity, correlates (mental health, nightmare characteristics) of
      reactivity, and consequences (sleep and health problems) of reactivity. Nightmare
      imagery resulted in significant reactivity relative to control imagery. No mental
      health variable (posttraumatic stress disorder status, depressive symptoms,
      dissociation) or nightmare characteristic (months experienced, frequency,
      similarity to trauma) was associated with reactivity level. However, nightmare
      imagery-evoked autonomic responses were associated with greater sleep disturbance
      and reported health symptoms, even when nightmare frequency was controlled. These
      results suggest nightmare-related autonomic reactions may contribute to sleep and
      health disturbance.

PMID- 18629688
TI  - Facets of impulsivity are differentially linked to insomnia: evidence from an
      exploratory study.
AB  - This study investigated the association between insomnia and four facets of
      impulsivity as distinguished by Whiteside and Lynam (2001): urgency, (lack of)
      premeditation, (lack of) perseverance, and sensation seeking. A sample of 233
      university students completed the UPPS Impulsive Behavior Scale, the Insomnia
      Severity Index, and a short questionnaire on sleep-related mentation.
      Correlational analyses revealed that urgency was related to insomnia severity and
      insomnia-related impairments in daytime functioning, and that lack of
      perseverance was related to insomnia-related impairments in daytime functioning.
      Follow-up analyses showed that the frequency of disturbing thoughts and visions
      during the pre-sleep period partially mediated the relation between urgency and
      sleep-initiation problems, and that the frequency of disturbing dreams and
      nightmares partially mediated the relation between urgency and sleep-maintenance
      problems. These findings suggest that the facets of impulsivity are
      differentially linked to insomnia and that urgency is associated with sleep
      interfering nighttime mentation.

PMID- 18629689
TI  - Psychometric evaluation of the Beck anxiety inventory: a sample with sleep
      disordered breathing.
AB  - This study aimed to document the psychometric properties of the Beck Anxiety
      Inventory (BAI) within a population with sleep-disordered breathing (SDB), given
      concerns about overlapping symptomatology between anxiety and sleep apnea.
      Results supported good internal consistency and convergent and discriminant
      validity for the BAI and a single-factor solution for men, women, and the total
      sample. Women had higher scores than men, and discriminant analyses
      differentiated men from women based on item responses. The BAI has acceptable
      reliability and validity within a SDB population, supporting its use as a gauge
      of anxiety severity in individuals with SDB. This is a preliminary study to
      measure anxiety severity in SDB; future research is needed to determine the
      utility of the BAI as a diagnostic screener.

PMID- 18629690
TI  - Total dietary intake of mercury in the Canary Islands, Spain.
AB  - Estimating the risk associated with dietary intake of heavy metals by consumers
      is a vital and integral part of regulatory processes. The assessment of exposure
      to mercury shown in this paper has been performed by means of a study on the
      whole diet. Total mercury (Hg) levels were determined by cold vapour atomic
      absorption spectrometry (AAS) in 420 samples of regularly consumed food and
      drink. The total Hg concentrations measured in the different groups of food
      ranged from non-detectable to 119 microg kg(-1) w/w. The fish group had the
      highest concentrations of total Hg. All groups of food with regulated Hg content
      showed levels that were lower than the legally set values. The food consumption
      data used in the analysis were taken from the latest nutritional survey made in
      the Canary Islands, Spain. The estimated total Hg intake of local population (5.7
      microg/person day(-1)) did not exceed the provisional tolerable weekly intake
      (PTWI) limit of 0.3 mg week(-1) of total mercury (43 microg/person day(-1)) fixed
      by the Joint Food and Agricultural Organization/World Health Organization
      (FAO/WHO) Expert Committee on Food Additives. Fishery products contributed 96% of
      the total Hg intake. The mean Hg intake for each island in this archipelago,
      formed by seven, has also been calculated. Fuerteventura, Lanzarote and El Hierro
      are the islands with the highest level of Hg intake (7.0, 7,0 and 6.1
      microg/person day(-1), respectively). La Palma Island, due to its low fish
      consumption, had the lowest level of Hg intake (4.5 microg/person day(-1)),
      followed by La Gomera (5.4 microg/person day(-1)), Tenerife (5.5 microg/person
      day(-1)) and Gran Canaria (5.6 microg/person day(-1)). A comparison has been made
      of the results obtained in this study with those found for other national and
      international communities.

PMID- 18629691
TI  - Context and contrast.

PMID- 18629692
TI  - 999 abuse: do mothers know what they are using?
AB  - Many parents purchase topical applications without knowing what they contain, and
      apply them liberally to their children with dermatological disorders. In one such
      case, an infant developed fever, diarrhea and a small ulcer near the right labia
      majora which was treated with a topical cream called '999' containing
      dexamethasone acetate. The infant subsequently developed extensive necrotizing
      fasciitis. She required prolonged intravenous antibiotic use and underwent
      multiple surgical procedures for debridement and reconstruction. Another mother
      was concerned about therapeutic corticosteroids prescribed to her 11-year old
      daughter with eczema. She acquired the 999 cream from the Chinese mainland and
      applied it liberally as an emollient to her daughter's back. When assessed at the
      clinic, her daughter appeared cushingoid with accelerated growth velocity in BMI
      and weight but decelerated growth in height. Furthermore, one mother applied a
      large quantity of 999 on her daughter with mild eczema and another mother applied
      it on her son with impetigo. None of these mothers knew that they were using
      potent topical corticosteroids. This report serves to alert the public to avoid
      applying unknown topical medication on children with skin diseases. The physician
      caring for patients with skin disease should be aware that even steroidophobic
      parents might indeed be unknowingly using potent corticosteroids.

PMID- 18629693
TI  - Botulinum toxin type A as an adjuvant treatment modality for extensive Hailey
      Hailey disease.
AB  - BACKGROUND: Extensive Hailey-Hailey disease is often resistant to conventional
      topical and systemic therapies. The systemic and ablative therapies have many
      side effects and/or high recurrence rates. Therefore, an alternative safe and
      effective treatment is needed. OBJECTIVE: To assess the effectiveness of
      botulinum toxin type A in the treatment of extensive Hailey-Hailey disease.
      METHODS: The cases of six patients with extensive Hailey-Hailey disease resistant
      to multiple therapeutic regimens were studied and described. Adjuvant therapy
      with botulinum toxin type A/Dysport was started in all six cases. RESULTS: Marked
      improvement of the lesions was achieved with few side effects in all patients.
      CONCLUSION: Botulinum toxin type A is a safe and effective adjuvant treatment for
      extensive Hailey-Hailey disease.

PMID- 18629694
TI  - Evaluation of public and worker exposure due to naturally occurring asbestos in
      gravel discovered during a road construction project.
AB  - During a repair and reconstruction project of an unpaved highway in a remote
      region of Alaska, workers discovered, after construction had commenced, that the
      materials used from a local material site contained asbestos (variously described
      as tremolite or actinolite). The regional geology indicated the presence of
      ultramafic rock, which often contains asbestos. Evaluation of asbestos exposure
      to workers, their equipment, and living quarters was required, as was the
      possible future exposure of workers and the general public to asbestos already
      used in the roadway construction. In addition, a decision was needed on whether
      to use materials from the contaminated site in the future. Of the almost 700
      breathing zone air monitoring samples taken of the workers, 3% of the samples
      indicated exposures at or near 0.1 f/cc by the National Institute for
      Occupational Safety and Health (NIOSH) 7400 phase contrast microscopy (PCM)
      procedure. Thirty-six of the PCM samples underwent transmission electron
      microscopy (TEM) analysis by the NIOSH 7402 procedure, which indicated that about
      40% of the fibers were asbestos. After classifying samples by tasks performed by
      workers, analysis indicated that workers, such as road grader operators who
      ground or spread materials, had the highest exposures. Also, monitoring results
      indicated motorist exposure to be much less than 0.1 f/cc. The design phase of
      any proposed construction project in regions that contain ultramafic rock must
      consider the possibility of amphibole contamination of roadway materials, and
      budget for exploration and asbestos analysis of likely materials sites.

PMID- 18629695
TI  - Introduction: Visual images and visualization in the neurosciences.

PMID- 18629696
TI  - Visual thinking and neuroscience.
AB  - After a consideration of visual thinking in science the role of such thinking in
      neuroscience is discussed. Three instances are examined - cortical column,
      retina, impulse - and it is argued that visual thinking is employed, though in
      different ways, in each. It lies at the core of neurobiological thought.

PMID- 18629697
TI  - Vision and visualization.
AB  - The art of visual communication is not restricted to the fine arts. Scientists
      also apply art in communicating their ideas graphically. Diagrams of anatomical
      structures, like the eye and visual pathways, and figures displaying specific
      visual phenomena have assisted in the communication of visual ideas for
      centuries. It is often the case that the development of a discipline can be
      traced through graphical representations and this is explored here in the context
      of concepts of visual science. As with any science, vision can be subdivided in a
      variety of ways. The classification adopted is in terms of optics, anatomy, and
      visual phenomena; each of these can in turn be further subdivided. Optics can be
      considered in terms of the nature of light and its transmission through the eye.
      Understanding of the gross anatomy of the eye and visual pathways was initially
      dependent upon the skills of the anatomist whereas microanatomy relied to a large
      extent on the instruments that could resolve cellular detail, allied to the
      observational skills of the microscopist. Visual phenomena could often be
      displayed on the printed page, although novel instruments expanded the scope of
      seeing, particularly in the nineteenth century.

PMID- 18629698
TI  - Brain, mind, and body: interactions with art in renaissance Italy.
AB  - The Renaissance saw the first systematic anatomical and physiological studies of
      the brain and human body because scientists, for the first time in centuries,
      were allowed to dissect human bodies for study. Renaissance artists were
      frequently found at dissections and their attention to detail can be observed in
      their products. Scientists themselves were increasingly artistic, and they
      created astonishing anatomical models and illustrations that can still be
      studied. The cross-fertilization of art and science in the Renaissance resulted
      in more scientific analyses of neuroanatomy as well as more creative ways in
      which such analyses could be depicted. Both art and science benefited from the
      reciprocal ways in which the two influenced each other even as they provided new
      ways of explaining the mysteries of the human body and mind.

PMID- 18629699
TI  - Neurological caricatures since the 15th century.
AB  - During the Renaissance, different artists began to draw medical illustrations
      from various viewpoints. Leonardo da Vinci was among those who sought to portray
      the emotional as well as the physical qualities of man. Other European artists
      described caricatural aspects of medical activities. In Northern Europe, Albrecht
      Durer, Hieronymus Bosch, and Pieter Brueghel were also famous for drawing
      caricatures. Later English artists, notably William Hogarth, Thomas Rowlandson,
      James Gillray, and the Cruikshanks, satirized life in general and the medical
      profession in particular. In Spain, Francisco Goya's works became increasingly
      macabre and satirical following his own mysterious illness and, in France, Honore
      Daumier used satire and humor to expose medical quackery. Also physicians such as
      Charles Bell and Jean-Martin Charcot were talented caricaturists. Their own
      personal artistic styles reflected their approach and gave a different "image" of
      neurology. Caricatures were popular portraits of developments in science and
      medicine and were frequently used whenever scientific language was too difficult
      to disseminate, in particular in the field of neurology.

PMID- 18629700
TI  - Visual images in Luigi Galvani's path to animal electricity.
AB  - The scientific endeavor that led Luigi Galvani to his hypothesis of "animal
      electricity," i.e., of an electricity present in a condition of disequilibrium
      between the interior and the exterior of excitable animal fibers, is reviewed
      here with particular emphasis to the role played by visual images in Galvani's
      path of discovery. In 1791 Galvani formulated his model of neuromuscular
      physiology on the base of the image of a muscle and a nerve fiber together as in
      a "minute animal Leyden jar." This was the last instance of a series of physical
      models that accompanied Galvani's experimental efforts in the search of a theory
      capable of accounting for the electric nature of nerve conduction in spite of the
      many objections formulated in the eighteenth century against a possible role of
      electricity in animal physiology.

PMID- 18629701
TI  - Light tries the expert eye: the introduction of photography in nineteenth-century
      macroscopic neuroanatomy.
AB  - It is often argued that photography's scientific inauguration meaningfully
      coincided with a shift towards the ideal of mechanical objectivity. Values of
      disinterestedness and precision were readily attributed to photography and were
      cherished by the emerging field of neurology as well. However, after the
      publication of the first neuroanatomical atlas to contain photographs, Jules
      Bernard Luys' Iconographie Photographique des Centres Nerveux (1873), the use of
      photography in macroscopic neuroanatomy remained rare. The present article
      sketches this largely overlooked terrain of investigation and will expand on why
      in macroscopical neuroanatomy photography failed to offer a satisfactory
      alternative to drawing or engraving.

PMID- 18629702
TI  - Recording the brain at work: the visible, the readable, and the invisible in
      electroencephalography.
AB  - The electroencephalogram (EEG), the graphic recording of the electric activity of
      the human brain, kindled far-reaching speculations about the imminent deciphering
      of mind and brain in the 1930s. Regardless of the thousands of neurons in the
      human cortex, recording from a person at rest produced a surprisingly regular
      line oscillating at 10 per second that disappeared at the moment of mental
      activity. With ever more groups specializing in electroencephalography, however,
      the deciphering of mind and brain did not materialize but moved further away in
      the information produced. In the various approaches employed in EEG research,
      such as the analysis of the graphic code, the search for pathognomic patterns or
      the imaging of cognitive processing, visualization guided research as well as
      theorizing, its productivity continued to keep the epistemological question open.

PMID- 18629703
TI  - The brains in Brain: the coevolution of localization and its images.
AB  - Images of brain localization from Brain's inception to the present are analyzed.
      Textual representations and their accompanying images are shown to coevolve; that
      is, the technological and conceptual development of the research program of
      localization is shown to evolve simultaneously with the exploitation of visual
      resources that support these developments. The semiotics of Peirce, the social
      semiotics of Kress and van Leeuwen, and the insights of Gestalt psychology
      provide a critical vocabulary with which to describe and to analyze these visual
      resources. I conclude that brain images evolve in a manner that reflects the
      uniformity in measuring instruments and the increase in their precision in the
      localization of brain functions; at the same time, they draw attention away from
      a persistent constraint: the brain functions so precisely localized are just
      those that are not constitutive of our humanity.

PMID- 18629704
TI  - NeurHistAlert 8.

PMID- 18629705
TI  - New proaporphines from the bark of Phoebe scortechinii.
AB  - The phytochemical study of the bark of Malaysian Phoebe scortechinii (Lauraceae)
      has resulted in the isolation and identification of two new proaporphine
      alkaloids; (+)-scortechiniine A (1) and (+)-scortechiniine B (2) together with
      two known proaporphines; (-)-hexahydromecambrine A (3), (-)
      norhexahydromecambrine A (4), and one aporphine; norboldine (5). Structural
      elucidations of these alkaloids were performed using spectroscopic methods
      especially 1D and 2D (1)H and (13)C NMR.

PMID- 18629706
TI  - Essential oil composition of three accessions of Dracocephalum heterophyllum
      Benth. cultivated at Palampur, India.
AB  - Seeds of three accessions of Dracocephalum heterophyllum growing wild in high
      altitude locations in the cold desert regions of trans-Himalaya were collected
      and propagated under polyhouse conditions at IHBT Palampur to evaluate, compare
      their growth performance and essential oil composition. Three different
      chemotypes viz., citronellol-rose oxides type, citronellol type and citronellal
      trans rose oxide type were identified. Samples of essential oils were distilled
      separately from leaves and inflorescence of all the three cultivated accessions
      and characterised by capillary GC and GC-MS techniques, which showed variation in
      the volatile constituents. In all the three accessions, citronellol was higher in
      the inflorescence oils as compared to leaf oils. Rose oxides, which are important
      high odour value cyclic monoterpene ethers were found in the essential oil
      samples of leaves as well as in the inflorescence of accession II, whereas these
      constituents were absent in the leaves of other two accessions. The essential oil
      from the inflorescence part of accession I was devoid of both cis and trans
      isomers of rose oxide, while accession III contained only one isomer of trans
      rose oxide. Under polyhouse conditions, seed germination was higher in accession
      III, whereas aerial biomass was higher in accession I. In comparison to other
      accessions, yield of volatile oil was higher in both leaf and inflorescence of
      accessions I, whereas accession II had higher oil yield from inflorescence. This
      is the first report of volatile oil composition of three accessions of D.
      heterophyllum cultivated at Palampur having potential as a new source of high
      valued essential oil for introduction in the perfumery industry.

PMID- 18629707
TI  - Benzofuran derivatives from Eupatorium fortunei.
AB  - A pair of epimers of benzofuranols and a benzofuran glucoside were isolated from
      a traditional Chinese medicine Eupatorium fortunei. Their structures and the
      relative stereochemistry were elucidated on the basis of the spectral analysis
      and chemical transformation as 3beta, 6-dimethyl-2, 3-dihydrobenzofuran-2alpha
      ol; 3beta, 6-dimethyl-2, 3-dihydrobenzofuran-2beta-ol and 3beta, 6-dimethyl-2, 3
      dihydrobenzofuran 2beta-O-beta-D-glucopyranoside.

PMID- 18629708
TI  - Bioactivities and chemical constituents of a Vietnamese medicinal plant Che Vang,
      Jasminum subtriplinerve Blume (Oleaceae).
AB  - Five crude extracts were made from leaves and stems of Jasminum subtriplinerve
      Blume (Oleaceae) and investigated for antimicrobial, antioxidant and cytotoxic
      activities. The extractions were done with petroleum ether, ethyl acetate,
      ethanol, methanol or water. All extracts exhibited anti-bacterial activity except
      the water fraction. On the other hand, all extracts exhibit antioxidant activity
      except the petroleum ether fraction using the DPPH radical scavenging assay. Only
      the petroleum ether fraction showed a cytotoxicity activity against tested cell
      lines, Hep-G2 and RD with IC(50) values of 19.2 and 20 microg mL(-1),
      respectively. From the petroleum ether and ethyl acetate extracts, two
      triterpenes namely 3beta-acetyl-oleanolic acid and lup-20-en-3beta-ol and a
      sterol, stigmast-5-en-3beta-ol were isolated. The structure of those compounds
      were elucidated by spectrometric methods IR, MS, 1D-NMR, 2D-NMR and simulated
      ACD/NMR spectra. The data presented here indicate that J. subtriplinerve do
      contain compounds with interesting biological activity.

PMID- 18629709
TI  - 1-O-Substituted derivatives of murrayafoline A and their antifungal properties.
AB  - The synthesis of some 1-oxygenated derivatives of murrayafoline A (1) and their
      antifungal properties is reported. Three derivatives, 1-hydroxy-3-methyl-9H
      carbazole (2), 1-(3-methylbut-2-enyloxy)-3-methyl-9H-carbazole (3) and 1
      (2,3,4,6,-tetra-O-acetyl-alpha-D-O-glucopyranosyl)-3-methyl-9H-carbazole (4), of
      murrayafoline A were synthesized. Compounds 1 and 2 exhibit strong fungicidal
      activity against Cladosporium cucumerinum at the dose of 12.5 microg.

PMID- 18629710
TI  - Fungistatic activity of iron-free bovin lactoferrin against several fungal plant
      pathogens and antagonists.
AB  - Lactoferrin (LF) is a member of the transferrin family of iron-binding
      glycoproteins. It is also a multifunctional protein of 80 kDa that is synthesized
      by glandular epithelial cells and secreted into mucosal fluid. High levels of LF
      are present in colostrom and milk and low levels in tears, saliva, and
      gastrointestinal and reproductive secretions. Data regarding the antifungal
      effects of LF are limited. Studies have been performed on Candida albicans, which
      demonstrated that LF inhibits the growth of this fungus. This study reports the
      results of experiments carried out in order to evaluate the effects of LF on the
      growth of 11 fungi, which were isolated from plants and soils. These experiments
      employed the methods of amended agar utilizing nine different concentration
      levels of LF (0, 0.001, 0.01, 0.1, 1, 10, 100, 1000, 5000 mg L(-1)). The effects
      of LF on the growth of these fungi were based on measures of the radial growth of
      the fungal colonies expressed both as percentage of inhibition and as IC(50)
      values (the concentration at which the fungal growth was inhibited by 50%
      relative to controls). LF had no effects on Alternaria alternata, Gliocladium
      roseum, Fusarium solani and Colletotrichum lindemuthianum. It did, however,
      inhibit the growth of Aspergillus niger, Trichoderma viride, Sclerotinia
      sclerotiorum, Sclerotium rolfsii, Rhizoctonia solani and Phoma exigua to the
      point that their IC(50) values ranged from 31.1 mg L(-1) for S. sclerotiorum to
      952 mg L(-1) for T. viride.

PMID- 18629712
TI  - Phytochemical analysis and in vitro cytotoxic activity of volatiles from
      Astragalus corniculatus.
AB  - The volatile fractions from Astragalus corniculatus Bieb., cultivated and
      collected wild, were analyzed at three different phenological phases for the
      first time. GC/MS analysis showed that the volatile fractions contain
      hydrocarbons, butyl ethers, acids, alcohols, esters, aldehydes, ketones,
      terpenes. These fractions were tested for cytotoxic activity in a panel of human
      tumor cell lines after 48 h, using the MTT-dye reduction assay. Throughout the
      cytotoxicity evaluation the fraction derived from the flowering phase of wild
      type plant was found to exert the most prominent cytotoxic activity, which could
      be ascribed to the high content of hydrocarbons and squalene in particular.
      Furthermore, the mechanistic elucidation of the mode of action of this volatile
      fraction in SKW-3 cells revealed that the observed activity is mediated by
      induction of necrotic type cell death as evidenced by the smear patterns of DNA
      following a 24 h exposure period.

PMID- 18629711
TI  - Anthraquinones from the roots of Prismatomeris malayana.
AB  - A novel anthraquinone, 1,3-dihydroxy-5,6-dimethoxy-2-methoxymethyl-9,10
      anthraquinone (9) and a new natural product, 2-hydroxymethyl-1-methoxy-9,10
      anthraquinone (8) were isolated from the roots of Prismatomeris malayana together
      with seven known anthraquinones, tectoquinone (1), 1-hydroxy-2-methyl-9,10
      anthraquinone (2), rubiadin (3), rubiadin-1-methyl ether (4), 1,3-dihydroxy-5,6
      dimethoxy-2-methyl-9,10-anthraquinone (5), nordamnacanthal (6), and damnacanthal
      (7). Their structures were determined on the basis of spectroscopic data. Some of
      the anthraquinones were tested for anticancer, antifungal, and antimalarial
      activities.

PMID- 18629713
TI  - The chemical composition of hexane extract from bark of Juniperus brevifolia.
AB  - The phytochemical analysis of the bark of Juniperus brevifolia was undertaken for
      the first time. The GC-MS analysis of the hexane extract from bark of "cedro-do
      mato" (J. brevifolia) allowed to identify three rare compounds for the first time
      in Juniperus genus: 6,7-dehydroferrugin-12-methyl ether, 11-hydroxy-6,7
      dehydroferruginol and 6,7-dehydrohinokiol. The results also showed that the
      chemical composition of the extract were essentially abietane-type diterpenoids
      with alcohol function (44.9%) and with carbonyl function (8.6%). Fatty acids such
      palmitic, oleic, stearic and docosanoic acids were the second most abundant
      family of identified compounds (9.5%) and its value increased (12.7%) after
      alkaline hydrolysis, mainly due to docosanoic and tetradocosanoic acids. Sterols
      like sitosterol and stigmast-4-en-3-one, were also present (6.6%), along with
      esters of sterols (8.4%). Significant quantities of the long-chain aliphatic
      alcohols (ca 3.7%) were identified in the hexane extract only after alkaline
      hydrolysis.

PMID- 18629714
TI  - Podophyllotoxin from suspension culture of Linum album.
AB  - Callus and suspension cultures of Linum album as an Iranian species for synthesis
      of aryltetralin lactone were used. After cultivation period; we can isolate and
      characterize podophyllotoxin as glycosides compounds. Maximal product yield is
      0.5% of the dry weight in dark grown cultures.

PMID- 18629715
TI  - Sesquilignans and dilignans from Campylotropis hirtella (Franch.) Schindl.
AB  - A new sesquilignan, erythro-Guaiacylglycerol-beta-O-4'-(5')-methoxylariciresinol,
      together with six known compounds including three sesquilignans and three
      dilignans, have been isolated from Campylotropis hirtella (Franch.) Schindl. that
      was used as traditional Chinese medicine for treatment of benign prostate
      hyperplasia. All these known compounds were found for the first time from the
      family leguminosae. The structure of the new compound and its relative
      configurations were elucidated on the basis of detailed spectroscopic analysis
      (NMR and MS). These compounds showed no obvious inhibition effect on prostate
      specific antigen secretion in LNCaP cells by ELISA method.

PMID- 18629716
TI  - Effects of European mistletoe (Viscum album L. subsp. album) extracts on activity
      rhythms of the Syrian hamsters (Mesocricetus auratus).
AB  - Antitumor drugs may have some significant nervous system side-effects such as
      disrupted sleep, eating and drinking patterns. European Mistletoe has been
      investigated for many decades for its potential use against cancer. To test the
      hypothesis that the non-antineoplastic effects of mistletoe might be mediated by
      the actions on the circadian timing system, we have applied mistletoe extracts
      and vehicle and have measured locomotor activity, feeding and drinking rhythms
      under constant darkness. Four groups (vehicle, 20 mg kg(-1) ip injection, 40 mg
      kg(-1) ip injection and 6 g kg(-1) oral administration) were performed for both
      heat-treated and freeze-dried extracts. None of the administrations changed the
      locomotor activity, feeding and drinking rhythms in the groups except for 40 mg
      kg(-1) freeze-dried injected group. The locomotor activity levels decreased in 40
      mg kg(-1) freeze-dried extract injected group. These results suggest that, side
      effects of mistletoe on circadian timing system of the Syrian hamster depend on
      the dose and the preparation method of the extract.

PMID- 18629717
TI  - A new secolactarane-type sesquiterpene from Strobilurus tephanocystis.
AB  - A new sesquiterpenoid, strobiluric acid has isolated from the liquid culture
      extract of the fungus Strobilurus stephanocystis together with seven known
      sesquiterpenoids. Their structures were established based on spectroscopic data.

PMID- 18629718
TI  - One new cinnamic imide dervative from the fruits of Tribulus terrestris.
AB  - One new cinnamic imide derivative, named tribulusimide C (1), was isolated from
      the fruits of Tribulus terrestris, together with three known compounds, N-p
      coumaroyltyramine (2), terrestriamide (3), N-trans-caffeoyltyramine (4). The
      structure of 1 was elucidated based on chemical analysis and spectral methods
      (IR, 1D and 2D NMR, HR-FAB-MS, EI-MS).

PMID- 18629719
TI  - Metaphoric identity mapping: facilitating goal setting and engagement in
      rehabilitation after traumatic brain injury.
AB  - Difficulty re-establishing an organised and compelling sense of personal identity
      has increasingly been identified as a critical theme in outcome studies of
      individuals with severe traumatic brain injury (TBI) and a serious obstacle to
      active engagement in rehabilitation. There exists little empirical support for
      approaches to identity reconstruction that address common impairments associated
      with TBI. Similarly, there is as yet little empirical support for theoretically
      sound approaches to promoting engagement in goal setting for this population.
      This article has two purposes. First, theory and procedures associated with
      metaphoric identity mapping are discussed in relation to goal setting in TBI
      rehabilitation. Second, the results of a qualitative pilot study are presented.
      The study explored metaphoric identity mapping as a facilitator of personally
      meaningful goal setting with five individuals with significant disability many
      years after their injury. Drawing on principles of grounded theory, the
      investigators extracted data from semi-structured interviews with clients and
      clinicians, from focus groups with the clinicians, and from observation of client
      clinician interaction. Analysis of the data yielded five general themes
      concerning the use of this approach: All clients and clinicians found identity
      mapping to be an acceptable process and also useful for deriving meaningful
      rehabilitation goals. Both clients and clinicians saw client-centred goals as
      important. Cognitive impairments posed obstacles to this goal-setting
      intervention and mandated creative compensations. And finally, identity-related
      goal setting appeared to require a "mind shift" for some clinicians and demanded
      clinical skills not uniformly distributed among rehabilitation professionals.

PMID- 18629720
TI  - What's new in Nicotine & Tobacco Research?

PMID- 18629721
TI  - Sociodemographic, insurance, and risk profiles of maternal smokers post the
      1990s: how can we reach them?
AB  - Declines in prenatal smoking rates have changed the composition of maternal
      smokers while public policy during the 1990s has likely made it more difficult to
      reach them. Medicaid expansions during the 1980s/early 1990s insured more women
      some time during pregnancy, but the 1996 welfare reform unexpectedly reduced
      enrollment in Medicaid by eligible pregnant women; overall, insurance coverage
      has declined since 2000. As the public sector struggles with fewer resources, it
      is important to understand the sociodemographic characteristics of prenatal
      smokers, their patterns of care, and nonsmoking risk behaviors. Targeting scarce
      dollars to certain settings or sub-populations can strengthen the infrastructure
      for tobacco policy change. We provide more current information on maternal
      smokers in 2002 based on the Pregnancy Risk Assessment Monitoring System (PRAMS)
      for 21 states. Data on urban/rural location, insurance coverage, access patterns,
      and nonsmoking risk behaviors (e.g., abuse) among low-income (<16,000) and other
      maternal smokers are included. Low-income maternal smokers are the working poor
      living in predominately urban areas with fewer health care resources than low
      income nonsmokers. Over 50% of low-income maternal smokers are uninsured pre
      pregnancy and use a clinic as their usual source of care. Regardless of income,
      smokers exhibit rates of nonsmoking risks that are two to three times those of
      nonsmokers and high rates of unintended pregnancy (68%) of low-income smokers.
      These characteristics likely call for a bundle of social support services beyond
      cessation for smokers to quit and remain smoke-free postpartum.

PMID- 18629722
TI  - Nicotine does not compromise resting myocardial blood flow autoregulation in
      smokers at high cardiovascular risk.
AB  - Nicotine has been recognized for years as being pharmacologically responsible for
      the sympathoexcitatory effects of smoking. The effects of nicotine
      supplementation on myocardial blood flow as assessed by positron emission
      tomography are, however, unknown. We tested the hypothesis that nicotine
      substitution could interfere with myocardial blood flow autoregulation at rest in
      habitual smokers at risk of coronary artery disease. The short-term effect of a 4
      mg nicotine tablet on myocardial blood flow was quantified with 13N ammonia
      positron emission tomography in 12 smokers with high cardiovascular risk (10
      males and 2 females; mean age = 58+/-8 years; SCORE risk >5%). Nicotine increased
      systolic blood pressure from 129+/-7 to 134+/-7 mmHg (p = .03) and heart rate
      from 67+/-2 to 69+/-2 bpm (p = .04). As a result, nicotine raised the rate
      pressure product from 8618+/-622 to 9285+/-627 bpm mmHg (p = .02). Nicotine
      tended to increase myocardial blood flow in the circumflex artery territory, but
      this effect failed to reach the level of statistical significance (from 0.56+/
      0.06 to 0.63+/-0.03 ml/min/g; p>.15). This trend disappeared when myocardial
      blood flow was normalized for the rise in the rate-pressure product. Global
      myocardial perfusion, normalized for the changes in rate-pressure product,
      remained unchanged from 0.70+/-0.06 at baseline to 0.71+/-0.03 (ml/min/g)/(bpm
      mmHg) after nicotine. Nicotine supplementation in habitual smokers with high
      cardiovascular risk increased myocardial work without compromising resting
      myocardial blood flow autoregulation.

PMID- 18629723
TI  - A randomized trial of nicotine replacement therapy in combination with reduced
      nicotine cigarettes for smoking cessation.
AB  - A randomized double-blind, active controlled, parallel group, multi-center phase
      II clinical trial was conducted to evaluate the efficacy of reduced-nicotine
      cigarettes as a novel smoking cessation treatment (under Investigational Device
      Exemption 69,185). The concept for a reduced-nicotine cigarette designed to
      progressively wean smokers from the smoking habit is based on research
      demonstrating that successful smoking cessation is not only dependent on
      withdrawal of nicotine, but also on weaning from the habitual sensory and
      behavioral reinforcement of smoking. Treatment consisted of Quest brand of
      cigarettes (Quest 1, 2, and 3), which respectively deliver 0.59+/-0.06, 0.3+/
      0.05, and less than 0.05 mg nicotine, either alone or in combination with
      nicotine replacement therapy (NRT). The primary endpoint was 4 weeks of
      continuous abstinence (Weeks 7-10), with additional follow-up at 3 and 6 months.
      Adult men and women smokers (N = 346), motivated to quit, were randomized to one
      of three treatment groups: Quest plus NRT (NRT pretreatment 2 weeks before, and
      NRT after the quit date), Quest plus placebo patch, or active control plus NRT
      (conventional cigarette, followed by NRT after quit date). Results showed that
      Quest plus NRT was more effective than active control plus NRT in achieving 4
      weeks of continuous abstinence (32.8% vs. 21.9%). Quest plus placebo patch
      yielded an abstinence rate similar to that of the active control plus NRT (16.4%
      vs. 21.9%). No serious adverse events were attributable to the investigational
      product. Quest plus NRT offers promise as a new smoking cessation treatment.

PMID- 18629724
TI  - Ad lib smoking in post-traumatic stress disorder: an electronic diary study.
AB  - Using ambulatory methods for 1 week of monitoring, this study investigated the
      association between smoking and situational cues in 22 smokers with post
      traumatic stress disorder (PTSD) and 23 smokers without PTSD. Generalized
      estimating equations contrasted 1,759 smoking and 1,088 nonsmoking situations by
      group status controlling for multiple covariates. PTSD smokers reported higher
      stress and PTSD symptoms across daily activities. For all smokers, higher
      nicotine dependence, craving, food and caffeine consumption, and being outside
      were related to smoking. PTSD smokers were more likely to smoke when experiencing
      PTSD symptoms, anxiety, and stress. Following smoking, smokers with PTSD reported
      a significant reduction in negative affect. These results are consistent with
      previous ambulatory findings regarding mood in smokers, and underscore that in
      smokers with PTSD, PTSD symptom variables as well as stress and anxiety are
      significantly associated with ad lib smoking.

PMID- 18629725
TI  - Is concern about post-cessation weight gain a barrier to smoking cessation among
      pregnant women?
AB  - Women who quit smoking during pregnancy gain more weight than women who continue
      to smoke. Concern about weight gain is a barrier to smoking cessation in the
      general population, but whether attitudes about weight are associated with
      failure to stop smoking during pregnancy or to maintain abstinence postpartum is
      unknown. Thus, attitudes about weight were assessed in 412 pregnant smokers
      recruited from obstetric practices in Massachusetts for a smoking cessation
      intervention trial. Smoking cessation outcomes (7-day point-prevalence abstinence
      by self-report and by cotinine-validation) were assessed at end-of-pregnancy and
      3 months postpartum. Bivariate and multivariable analyses assessed the
      relationship between attitudes about weight and smoking cessation. In bivariate
      analyses, a high level of concern about post-cessation weight gain was associated
      with older age (p = .01), smoking more cigarettes/day (p<.001), not making a quit
      attempt in pregnancy (p = .02), being less likely to self-report tobacco
      abstinence at end of pregnancy (p = .01) and postpartum (p = .02), and having
      less cotinine-validated abstinence at 3 months postpartum (p = .05). In
      multivariable analyses that adjusted for cigarettes/day, a low level of concern
      about post-cessation weight gain was associated with more self-reported
      abstinence at end-of-pregnancy (OR = 1.77, 95% CI 1.01-3.09) and postpartum (OR =
      2.09, 95% CI 1.05-4.14), but not with cotinine-validated abstinence at end-of
      pregnancy (OR = 1.30, 95% CI 0.63-2.68) or postpartum (OR = 2.18, 95% CI 0.93
      5.10). In conclusion, women who are more concerned about post-cessation weight
      gain may be less likely to quit smoking during pregnancy or remain abstinent in
      the postpartum period.

PMID- 18629727
TI  - Effects of nicotine on affect are moderated by stressor proximity and frequency,
      positive alternatives, and smoker status.
AB  - The Situation x Trait Adaptive Response (STAR) model hypothesizes that nicotine
      reduces negative and enhances positive affect to a greater degree in situations
      involving internally driven attention, as when stressor stimuli are distal (past
      or future), thereby allowing nicotine-primed biasing of attentional processing
      away from negative and toward positive stimuli. To test this hypothesis, the
      effects of nicotine were assessed in 64 smokers and 64 never-smokers, half of
      whom viewed emotionally negative pictures in a no-choice picture attention task
      that required them to focus on the picture stressors. The other half viewed the
      same stimuli in a two-choice picture attention task that presented stressor
      pictures in one visual field and simultaneously presented positive or neutral
      pictures in the other visual field. Participants received a nicotine patch during
      one session and a placebo patch during the other session. Nicotine modulated
      affect only in smokers. In smokers, compared with placebo, nicotine patch reduced
      negative affect more during the distal periods (between stressors) than during
      actual stressor exposure and in women reduced negative affect more when the
      proportion of negative stimuli was low. Nicotine also enhanced positive affect
      more during distal than proximal stressors. Nicotine tended to reduce eye-gaze at
      negative pictures, especially when the alternative picture was positive. The
      overall findings are consistent with the view that nicotine biases attention away
      from negative stimuli when equally salient positive or benign stimuli are
      present.

PMID- 18629726
TI  - Real-time craving and mood assessments before and after smoking.
AB  - This study explored some quandaries concerning craving and mood as motivators to
      smoke. Craving and negative mood have long been associated with day-to-day
      smoking as two of the primary motivational forces behind the maintenance of the
      behavior, as well as significant barriers in smokers' attempts to quit. Craving
      remains a clinically relevant phenomenon, with most smokers describing craving as
      a troublesome problem when quitting. Smokers' self-reports of negative mood, as
      an antecedent for smoking, are so robustly reported that many models of nicotine
      dependence have incorporated a critical role for negative mood in maintaining
      smoking behavior. However, several naturalistic studies that collected mood
      ratings with hand held computers from smokers in real time, just before smoking a
      cigarette, have provided scant evidence that negative mood plays a major role in
      motivation to smoke. No study to date has examined craving and mood data as a
      consequence of smoking, that is, collecting the same data immediately after
      smoking. This study used personal digital assistants (PDAs) to collect craving
      and mood data immediately before smoking, immediately after smoking, and at
      random times of day. Nontreatment seeking smokers (N = 72) carried a PDA for an
      average of 10 days while they recorded their smoking behavior. Results showed
      that craving and negative mood ratings were lowest immediately after smoking
      compared with immediately before smoking and at random times of day. These
      findings suggest that smokers may be at least partially motivated to smoke to
      lower their craving and improve their mood states.

PMID- 18629728
TI  - Ecological momentary assessment of adolescent smoking cessation: a feasibility
      study.
AB  - Attempts to quit smoking by adolescents typically fail, even when aided by
      psychosocial and pharmacological treatments. Gaining a better understanding of
      the process of smoking cessation and relapse in this population could lead to
      improved treatments and increases in cessation rates. Ecological momentary
      assessment (EMA) has been used to describe the relapse process among adults, but
      not among adolescents. This study examined the feasibility of using EMA to
      examine relapse among adolescent smokers. Participants (N = 13) used a hand-held
      computer for 3 weeks to report on their smoking behavior, affect state, and
      exposure to smoking cues during a quit attempt (7 days prequit, 14 days
      postquit). All of the participants recorded a quit attempt and at least one lapse
      during the monitoring interval. Compliance with the protocol was generally high
      but decreased slightly over time. As with adults, evidence indicated that lapses
      were associated with craving, negative affect, and smoking cues. These data
      support the feasibility and potential value of using EMA with adolescent smokers.

PMID- 18629729
TI  - An analysis of messages about tobacco in the Military Times magazines.
AB  - The Military Times magazines are seen as an independent source of news and
      information on the military and are widely read by military members. Given the
      influence of Military Times as a powerful media outlet within the military and
      marketing to military personnel by the tobacco industry, we examined tobacco
      messages and advertisements in a one-year sample from each service. No
      advertisements for cigarettes or other forms of smoked tobacco were found in any
      issue published in 2005. However, smokeless tobacco products were advertised
      frequently, with 11 distinct ads occurring in 105 ad placements. During the year
      targeted in the present study, smokeless tobacco advertising generated
      approximately US$564,249 in revenue for the publishers of Military Times. A
      content analysis suggested that the advertisements intended to pair smokeless
      tobacco use with a pleasant mood and enjoyable events not directly associated
      with the product itself. In addition, magazine articles about anti-tobacco topics
      received among the lowest amount of coverage among all pro-health articles. These
      findings may partially explain the recent significant increase in smokeless
      tobacco use among military personnel.

PMID- 18629730
TI  - The impact of smoking on health-related and overall quality of life: a general
      population survey in Finland.
AB  - The objective of the study was to examine the association between overall and
      health-related quality of life and smoking in men and women of discrete smoking
      groups in Finland. The design was a Health 2000 Survey, conducted in Finland 2000
      -2001. The setting and participants were a two-stage, stratified, nationally
      representative cluster sample that comprised 8,028 persons aged 30 or over living
      in mainland Finland. Health-related quality of life was measured by the 15D
      questionnaire; and overall quality of life was assessed by a single question
      measure capturing the respondent's own perception and estimation of his/her
      quality of life. The present study showed that daily smokers had both lower
      health-related and overall quality of life than never-smokers among the Finnish
      adult population. Health-related quality of life profiles showed that daily
      smokers did worse than never-smokers in a considerable number of the health
      dimensions. The effects of smoking were observed not only through health: the
      daily smokers registered significantly lower ratings of overall quality of life
      compared with never-smokers, too. Both the health-related and overall quality of
      life of ex-smokers approached those of never-smokers. The results of the present
      study suggest that improved health is not the only benefit of smoking cessation;
      better quality of life and more fulfilling everyday living can also be expected.
      As the major health consequences of smoking usually manifest themselves only
      after several years of smoking, both health-related and overall quality of life
      measurements could be used as an intervention tool for motivating people to quit.

PMID- 18629731
TI  - Use of flavored cigarettes among older adolescent and adult smokers: United
      States, 2004--2005.
AB  - Cigarettes with candy, fruit and alcohol flavors have been introduced in recent
      years as extensions to popular cigarette brands, raising concerns in the public
      health community that the enticing names, creative packaging, and intense
      flavorings of these products may be especially appealing to youth. This study
      used two national surveys to examine the prevalence of use of Camel Exotic
      Blends, Kool Smooth Fusion, and Salem Silver Label brands during 2004--2005 among
      older adolescents and young adult smokers aged 17-26 years and adult smokers aged
      > or =25 years. Overall use of any of these flavored brands in the past 30 days
      was 11.9% among smokers aged 17-26 years and 6.7% among smokers aged > or =25
      years. A significant gradient in use was seen across age, with the highest rates
      of utilization among 17-year-old (22.8%) and 18-19-year-old smokers (21.7%)
      (p<.001). Uniquely flavored cigarette brands seem to be most attractive to the
      youngest smokers and should be prohibited.

PMID- 18629732
TI  - Randomized trial of a smoking cessation intervention in hospitalized patients.
AB  - A hospitalization is a time when perceived vulnerability to dangers from smoking
      and quitting motivation may be at their peak. Aim was to determine whether a
      smoking cessation intervention of moderate intensity would increase the smoking
      cessation rate in hospitalized smokers. Design was randomized trial, conducted in
      a university-affiliated cardio-pulmonary tertiary care center. Participants were
      hospitalized smokers aged < or =70 years. Intervention was a smoking cessation
      intervention consisting of education and psychological support, with or without
      pharmacological therapy, associated with follow-up phone calls. Patients assigned
      to the control group received usual care. Measurement was point prevalence
      cessation rate at 1-year follow-up. A total of 468 patients were screened; 196
      were randomized. Although the smoking cessation rates at 12-month follow-up were
      higher than expected, we found no significant difference between the study groups
      (intervention: 30.3%; control: 27.8%). Similar results were obtained in patients
      whose smoking status was validated by urinary cotinine assay. Length of stay and
      dependence to nicotine were the only significant predictors of smoking cessation.
      A smoking cessation intervention of moderate intensity delivered in a tertiary
      cardio-pulmonary center did not increase the smoking cessation rate at 1-year
      follow-up. The results of this trial should not divert those who deliver care to
      inpatients from delivering a brief smoking cessation intervention.

PMID- 18629733
TI  - Race differences in nicotine dependence in the Collaborative Genetic study of
      Nicotine Dependence (COGEND).
AB  - In a general population sample from the Detroit site of the Collaborative Genetic
      Study of Nicotine Dependence (COGEND), we tested Black-White differences in
      nicotine dependence, measured by "how soon after wake-up the smokers smoked their
      first cigarette (time to first cigarette TTFC)", and its relationship with number
      of cigarettes per day (CPD). Analysis was conducted on respondents who have
      smoked > or =100 cigarettes in lifetime and were current smokers (n = 1,442;
      1,087 Whites and 355 Blacks). In univariate analysis, we found no significant
      race differences on time to first cigarette (chi2 = 2.9, p value = 0.41), but
      significant race differences on CPD (chi2 = 154.3, p<.01), both categorized by
      the Fagerstrom Test of Nicotine Dependence (FTND) cutoffs. We estimated the
      probability of TTFC < or =30 min given CPD using probit models. The interactions
      between race and CPD indicated significant differences in dependence at various
      levels of CPD. The same probability of nicotine dependence was associated with
      smaller increments in CPD for Blacks than for Whites. The data support the
      hypothesis that the relationship between CPD and nicotine dependence as reflected
      in relapse varies by race, and that Black smokers are dependent at lower levels
      of CPD than Whites.

PMID- 18629734
TI  - Is the smoking-depression relationship confounded by alcohol consumption? An
      analysis by gender.
AB  - There is a well-established relationship between cigarette smoking and
      depression. The purpose of the current study is to examine whether alcohol use
      may be a confounder in this relationship, and whether this relationship differs
      between men and women. As part of a national survey, 14,063 Canadians were
      interviewed using random-digit dialing and computer-assisted telephone
      interviewing. Responses to questions on smoking during the past 12 months allowed
      participants to be classified as never, former, light, mid-level, and heavier
      smokers. Alcohol use measures included: usual frequency, usual quantity per
      drinking occasion, heavy episodic drinking (5 or more drinks), and hazardous
      drinking. Depression was measured as (a) meeting clinical diagnostic criteria for
      depression (Composite International Diagnostic Interview) and (b) recent
      depressed affect (Center for Epidemiological Studies of Depression scale).
      Multinomial logistic regressions indicated that the association between smoking
      and depression was only slightly reduced and remained significant when drinking
      status and drinking pattern were controlled for. The relationship between smoking
      and depression was stronger for women when depression was measured as meeting
      clinical criteria for depression, with all categories of smoking by women but
      only mid-level and heavier smoking by men significant related to depression.

PMID- 18629735
TI  - Sex differences in long-term smoking cessation rates due to nicotine patch.
AB  - Compared to men, women may be at greater risk for smoking-related diseases and
      have greater difficulty quitting smoking. Sex differences in medication response
      could guide treatment for smoking cessation to improve women's quit rates. We
      conducted a meta-analysis of the 14 placebo-controlled nicotine patch trials (N =
      6,250) for which long-term (6 months) clinical outcome results could be
      determined separately by sex. This analysis updated a meta-analysis of 11 of
      these trials that found no significant sex differences due to nicotine patch. The
      increase in quitting due to the nicotine vs. placebo patch was only about half as
      large in women as in men. Pooled absolute quit rates at 6 months for nicotine and
      placebo patch, respectively, were 20.1% and 10.8% in men, and 14.7% and 10.1% in
      women. The odds ratio for quitting due to nicotine vs. placebo patch was lower in
      women (OR = 1.61) than in men (OR = 2.20), with an interaction odds ratio of 1.40
      (95% CI = 1.02-1.93, p = .04). This sex difference did not vary significantly by
      whether or not formal counseling was provided. Poorer outcomes in women vs. men
      treated with nicotine patch suggests that increasing the quit rates of women
      smokers may require supplementing patch treatment or use of other medications.

PMID- 18629736
TI  - Preliminary examination of tobacco withdrawal in adolescent smokers during
      smoking cessation treatment.
AB  - Tobacco withdrawal symptoms have been shown to play a significant role in
      mediating relapse to smoking in adult smokers; however, few prospective studies
      have examined the course of tobacco withdrawal symptoms over time and their
      connection to lapse in adolescent smokers. Withdrawal symptoms were assessed
      weekly for 4 weeks in a sample of adolescent smokers participating in a pilot
      cessation intervention. Adolescent smokers experienced an exacerbation in overall
      withdrawal symptoms, particularly of cravings and restlessness, although symptoms
      were generally mild. The course of symptoms was different for boys and girls:
      Girls generally experienced a peak and subsequent decline in symptoms early in
      the establishment of abstinence, whereas boys experienced a constant level of
      symptoms that did not decline over the 4 weeks. Finally, withdrawal symptoms
      experienced on quit day were not related to lapse to smoking during the course of
      treatment for either boys or girls. These results suggest that although
      withdrawal symptoms may be uncomfortable, they may not be the most salient to a
      lapse to smoking for adolescent smokers attempting to quit. These findings have
      direct implications for the design and implementation of treatment of nicotine
      dependence in adolescent smokers.

PMID- 18629737
TI  - Automated determination of seven phenolic compounds in mainstream tobacco smoke.
AB  - Exposure to hydroxyl-substituted arenes, commonly referred to as phenols or
      phenolic compounds, can have serious health consequences. Select phenols present
      in tobacco smoke are cardiovascular toxins, act as tumor co-promoters and show
      genotoxic activity. To examine the mainstream smoke levels of these compounds, we
      developed and applied a method for quantitative analysis of seven phenols
      (phenol, o-cresol, m-cresol, p-cresol, catechol, resorcinol, and hydroquinone) in
      mainstream smoke. Total mainstream smoke particulate matter was collected on a
      Cambridge filter pad and spiked with an isotopically labeled internal standard
      solution. This pad underwent an automated phenol derivatization procedure to
      increase analyte volatility and enhance detection. Following the derivatization
      step, phenols from the particulate matter were sampled using solid-phase
      microextraction with subsequent gas chromatography/mass spectrometric detection.
      Sensitivity, selectivity, accuracy, and reproducibility were more than adequate
      for routine detection of phenols in mainstream smoke. Detection limits ranged
      from 0.04-0.57 microg, with a quantification range of 0.1-710 microg. Higher
      sensitivity and sample throughput were achieved compared with previously
      described methods. Mainstream smoke from 28 brands of domestic commercial
      cigarettes was evaluated to assess typical levels, and reference cigarettes
      containing single tobacco blends were examined to ascertain the phenolic profile
      from different types of tobaccos. As expected under machine smoking conditions
      using the Federal Trade Commission parameters, full-flavored cigarettes deliver
      more phenols than the light varieties, followed by the ultra light varieties.
      Differences were seen in relative levels of phenolic compounds in the mainstream
      smoke from unfiltered cigarettes made with a single type of tobacco.

PMID- 18629738
TI  - Perfectly misleading distances from ternary characters.
AB  - D. Huson and M. Steel showed that for any two binary phylogenetic trees on the
      same set of n taxa, there exists a sequence of multistate characters that is
      homoplasy-free only on the first tree but perfectly additive only on the second
      one. The original construction of such a sequence required n - 1 character states
      and it remained an open question whether a sequence using fewer character states
      can always be found. In the present note we will answer this question by showing
      that three character states suffice to construct such misleading sequences--even
      if we insist that they conform to an ultrametric (i.e., fit a molecular clock).

PMID- 18629739
TI  - Grasping visual illusions: Consistent data and no dissociation.
AB  - The finding that the Ebbinghaus/Titchener illusion deceives perception but not
      grasping is usually seen as strong evidence for Goodale and Milner's (1992)
      notion of two parallel visual systems, one being conscious and deceived by the
      illusion (vision-for-perception) and the other being unconscious and not deceived
      (vision-for-action). However, this finding is controversial and led to studies
      with seemingly contradictory results. We argue that these results are not as
      contradictory as it might seem. Instead, studies consistently show similar
      effects of the illusion on grasping. The perceptual effects are strongly
      dependent on the specific perceptual measure employed. If, however, some
      methodological precautions are used, then these diverse perceptual results can be
      reconciled and point to a single internal size estimate that is used for
      perception and for grasping. This suggests that the Ebbinghaus illusion deceives
      a common representation of object size that is used by perception and action.

PMID- 18629740
TI  - Optimal mechanical design of anatomical post-systems for endodontic restoration.
AB  - This paper analyses the mechanical behaviour of a new reinforced anatomical post
      systems (RAPS) for endodontic restoration. The composite restorative material
      (CRM) completely fills the root canal (as do the commonly used cast metal posts)
      and multiple prefabricated composite posts (PCPs) are employed as reinforcements.
      Numerical simulations based on 3D linearly elastic finite element models under
      parafunctional loads were performed in order to investigate the influence of the
      stiffness of the CRM and of the number of PCPs. Periodontal ligament effects were
      taken into account using a discretised anisotropic nonlinearly elastic spring
      system, and the full discrete model was validated by comparing the resulting
      stress fields with those obtained with conventional restorations (cast gold-alloy
      post, homogeneous anatomical post and cemented single PCP) and with the natural
      tooth. Analysis of the results shows that stresses at the cervical/middle region
      decrease as CRM stiffness increases and, for large and irregular root cavities
      that apical stress peaks disappear when multiple PCPs are used. Accordingly, from
      a mechanical point of view, an optimal RAPS will use multiple PCPs when CRM
      stiffness is equal to or at most twice that of the dentin. This restorative
      solution minimises stress differences with respect to the natural tooth,
      mechanical inhomogeneities, stress concentrations on healthy tissues, volumes
      subject to shrinkage phenomena, fatigue effects and risks of both root fracture
      and adhesive/cohesive interfacial failure.

PMID- 18629741
TI  - Individual differences in the preferred neck-resting position of Caribbean
      flamingos (Phoenicopterus ruber).
AB  - When resting, flamingos often lay their heads along their backs. While in this
      position they must curve their necks to either the right or left of their
      midline. Observations of captive Caribbean flamingos at the Philadelphia Zoo
      (Philadelphia, PA, USA) were conducted in order to determine if individual birds
      would display consistent preferences in neck-resting position over multiple
      observations. While individual birds were shown to vary greatly in regards to the
      strength and direction of their preferences, a significant flock-level preference
      towards neck resting to the right was obtained. Analysis of individual flamingos
      revealed that 5 out of 17 birds displayed preferences that significantly differed
      from chance, with each of these birds preferring to rest their necks to the
      right. From the present data we can conclude that flamingos display behavioural
      laterality of neck-resting position at both the level of the group and that of
      the individual.

PMID- 18629742
TI  - Posttraumatic stress disorder: future directions in science and practice.

PMID- 18629743
TI  - Overlap of mild TBI and mental health conditions in returning OIF/OEF service
      members and veterans.

PMID- 18629744
TI  - Posttraumatic stress disorder and health functioning in a non-treatment-seeking
      sample of Iraq war veterans: a prospective analysis.
AB  - To evaluate the impact of posttraumatic stress disorder (PTSD) on health-related
      functioning, we assessed 800 U.S. Army soldiers before and after 1-year military
      deployments to Iraq. As part of the Neurocognition Deployment Health Study
      procedures, each soldier completed at both time points self-report indexes of
      PTSD symptom severity, health behaviors (smoking, alcohol use), and somatic
      health-related functioning. Participants also completed a health-symptom
      checklist at the postdeployment assessment. Structural equation modeling revealed
      that postdeployment PTSD severity was associated with change in somatic health
      related functioning, with postdeployment health symptoms as an intermediary
      variable. These relationships were independent of health risk behaviors, which
      had little association with somatic symptoms or PTSD. Our findings highlight the
      functional impact of PTSD, which extends beyond psychological symptoms to health
      related daily functioning.

PMID- 18629745
TI  - Structural equation modeling of associations among combat exposure, PTSD symptom
      factors, and Global Assessment of Functioning.
AB  - This study used structural equation modeling (SEM) to evaluate the relative
      strength of associations between combat exposure, four posttraumatic stress
      disorder (PTSD) symptom factors, and functional impairment as indexed by Global
      Assessment of Functioning (GAF) scores in a sample of 315 veterans assessed at a
      Department of Veterans Affairs PTSD clinic. Results showed that the association
      between combat exposure and GAF scores was fully mediated by PTSD severity. The
      best-fitting model included direct paths from combat exposure to reexperiencing
      symptoms and from avoidance and numbing symptoms to GAF. However, only 17% of
      variance in GAF was accounted for by PTSD. The results raise concern about the
      use of the GAF score as a benchmark for quantifying combat PTSD-related
      functional impairment.

PMID- 18629746
TI  - Patient factors relating to detection of posttraumatic stress disorder in
      Department of Veterans Affairs primary care settings.
AB  - We examined the impact of patient-level factors on provider recognition of
      posttraumatic stress disorder (PTSD). Analyses were based on a random sample of
      1,079 consenting patients who had an outpatient visit at any of four southeastern
      Department of Veterans Affairs hospitals in 1999. We collected data on PTSD
      symptoms, sociodemographics, functional status, medical record diagnoses, and
      independent PTSD diagnostic assessments for 888 patients. Complete and usable
      data were available for 819 patients. A total of 98 patients (12%) met criteria
      for PTSD, and of these, 42 (43%) were correctly classified as such by their
      provider. Results indicate that age (50-64), war-zone service, worse functioning
      on the 36-Item Short Form Health Survey role emotional subscale, a diagnosis of
      musculoskeletal pain, a greater percentage of persistent reexperiencing or
      avoidance/numbing symptoms, and a previously diagnosed substance use disorder
      were all independently related to provider recognition of PTSD. Knowledge of
      these factors may help inform providers and direct improved screening and case
      finding.

PMID- 18629747
TI  - Exploration of gender differences in how quality of life relates to posttraumatic
      stress disorder in male and female veterans.
AB  - Significant gaps exist in our knowledge about gender differences in quality of
      life among individuals with posttraumatic stress disorder (PTSD). We addressed
      these gaps by using data from two randomized clinical trials of veterans treated
      in Department of Veterans Affairs settings: 358 male Vietnam veterans who
      received group therapy and 203 female veterans who received individual
      psychotherapy. Using confirmatory factor analysis, we found that a four-factor
      structure for the Quality of Life Inventory provided the best fit for both
      groups. Overall quality of life was poor in men and women, and in general, they
      did not differ in quality of life or in how PTSD was associated with quality of
      life; the few statistically significant differences were small and clinically
      insignificant. For both men and women, numbing was uniquely associated with
      reduced quality of life. We suggest that quality of life should receive increased
      attention in research and clinical efforts to help veterans with PTSD.

PMID- 18629748
TI  - Risk factors for mental, physical, and functional health in Gulf War veterans.
AB  - Risk factors associated with war-zone events and circumstances are implicated in
      the health and adjustment of military veterans. We assessed a national stratified
      sample of community-residing veterans of the Gulf War (N = 357) using scales from
      the Deployment Risk and Resilience Inventory, along with an array of mental
      (posttraumatic stress disorder, depression, and anxiety), physical (symptom and
      condition indicators especially pertinent to Gulf War illnesses), and functional
      (both mental and physical dimensions) health outcomes. We found that perceived
      threat or fear of bodily harm in the war zone and self-reported or perceived
      exposures to environmental hazards may play a critical role in all measured
      aspects of health. Moreover, a synergistic effect of these two risk factors was
      observed in the prediction of mental health and mental health functional status.

PMID- 18629749
TI  - Sexual harassment and assault experienced by reservists during military service:
      prevalence and health correlates.
AB  - The current investigation identified the gender-specific prevalence of sexual
      harassment and assault experienced during U.S. military service and the negative
      mental and physical health correlates of these experiences in a sample of former
      reservists. We surveyed a stratified random sample of 3,946 former reservists
      about their experiences during military service and their current health,
      including depression, posttraumatic stress disorder, somatic symptoms, and
      medical conditions. Prevalence estimates and confidence intervals of sexual
      harassment and assault were calculated. A series of logistic regressions
      identified associations with health symptoms and conditions. Both men and women
      had a substantial prevalence of military sexual harassment and assault. As
      expected, higher proportions of female reservists reported sexual harassment
      (60.0% vs 27.2% for males) and sexual assault (13.1% vs 1.6% for males). For both
      men and women, these experiences were associated with deleterious mental and
      physical health conditions, with sexual assault demonstrating stronger
      associations than other types of sexual harassment in most cases. This
      investigation is the first to document high instances of these experiences among
      reservists. These data provide further evidence that experiences of sexual
      harassment and assault during military service have significant implications for
      the healthcare needs of military veterans.

PMID- 18629750
TI  - Posttraumatic stress disorder symptoms in Bosnian refugees 3 1/2 years after
      resettlement.
AB  - This study describes the evolution of trauma-related symptoms over 3 1/2 years in
      a group of Bosnian refugees. Twenty-one refugees received standardized
      psychological assessments shortly after arriving in the United States and then 1
      year and 3 1/2 years later. Of these refugees, 76% met diagnostic criteria for
      posttraumatic stress disorder (PTSD) at baseline, 33% at 1 year, and 24% at 3 1/2
      years. PTSD severity scores in women refugees were higher than scores in men at
      all three evaluation time points. At the 3 1/2-year evaluation, 44% of women and
      8% of men met criteria for PTSD and no correlation was found between PTSD symptom
      severity and either age or level of trauma exposure. A significant inverse
      correlation was found between Global Assessment of Functioning (GAF) scores and
      PTSD severity scores. Refugees who reported better mastery of the English
      language had significantly higher GAF scores. Although PTSD symptom severity
      decreased over time, most refugees continued to have at least one or more trauma
      related symptoms and 24% still met criteria for PTSD after 3 1/2 years in the
      United States. Women refugees and those who had not mastered the English language
      appeared to be more vulnerable to persisting psychological effects of trauma.

PMID- 18629751
TI  - Posttraumatic stress disorder and employment in veterans participating in
      Veterans Health Administration Compensated Work Therapy.
AB  - Few studies have examined employment outcomes in individuals with a primary
      diagnosis of posttraumatic stress disorder (PTSD). The current study used
      multivariate modeling to examine the relationship between PTSD, other aspects of
      military service, and employment among 5,862 veterans in a national Department of
      Veterans Affairs (VA) vocational rehabilitation program. Veterans with PTSD were
      19% less likely to be employed at discharge (odds ratio = 0.81, p = 0.02) after
      controlling for potentially confounding variables. Individuals with substance use
      diagnoses or who were homeless at program entry were more likely to be employed
      at discharge, while receipt of public support income and severe mental illness
      decreased the likelihood of being competitively employed. This study supports
      current VA efforts to expand and improve the effectiveness of vocational
      rehabilitation services for veterans with PTSD.

PMID- 18629753
TI  - Right anterior cingulate cortical volume covaries with respiratory sinus
      arrhythmia magnitude in combat veterans.
AB  - Existing data suggest anterior cingulate cortex (ACC) plays a role in autonomic
      regulation. In persons with posttraumatic stress disorder (PTSD), autonomic
      regulation appears impaired and smaller mean ACC volume has been reported. This
      study examined relationships between ACC volume and the magnitude of respiratory
      sinus arrhythmia (RSA) in 77 U.S. combat veterans at rest, 40 of whom met
      criteria for PTSD. RSA magnitude did not differ in combat survivors with and
      without PTSD, which contradicts studies comparing civilians with PTSD to
      nontraumatized controls. RSA magnitude was positively correlated with right but
      not left hemisphere ACC volume. This finding was statistically independent of the
      presence or absence of PTSD.

PMID- 18629752
TI  - Intensity dependence of auditory P2 in monozygotic twins discordant for Vietnam
      combat: associations with posttraumatic stress disorder.
AB  - Two studies have reported decreased intensity dependence of the P2 event-related
      potential (ERP) in male combat veterans with posttraumatic stress disorder
      (PTSD), a response pattern presumed to reflect central nervous system-induced
      protective inhibition and heightened central serotonergic activity. We used an
      identical twin, case-control design to investigate whether intensity dependence
      abnormalities reflect pretrauma vulnerability or are an acquired consequence of
      PTSD. ERPs were measured in male Vietnam combat veterans and their noncombat
      exposed monozygotic twin brothers during a four-tone, stimulus-intensity
      modulation procedure. Contrary to previous findings in male veterans, the PTSD
      group had significantly steeper P2 amplitude intensity slopes, similar to those
      reported for female veterans and abused children with PTSD. Additionally,
      increased P2 amplitude intensity slope was associated with increased PTSD symptom
      severity, particularly the severity of reexperiencing symptoms. A mixed-model,
      random-effects analysis that included the combat-unexposed twins revealed a
      significant diagnosis by combat exposure interaction. Inspection of group means
      suggests that the observed increased P2 intensity dependence is a consequence of
      PTSD. Our findings further suggest that low serotonergic tone may emerge as one
      potential consequence of this disorder.

PMID- 18629754
TI  - Psychometric properties of PTSD Checklist in sample of male veterans.
AB  - The psychometric properties of the PTSD Checklist (PCL) were investigated in a
      sample of treatment-seeking and community-dwelling male veterans. In conjunction
      with previous reports, results from the present study indicate that the PCL
      possesses strong, robust psychometric properties. The current investigation
      suggests a cutoff score of 60-higher than previous investigations-related to
      posttraumatic stress disorder (PTSD) diagnosis derived from the Clinician
      Administered PTSD Scale. This research supports the use of the PCL as a brief
      self-report measure of PTSD symptomatology.

PMID- 18629755
TI  - [Role of surgery in multimodal treatment of oral and oropharyngeal cancer].
AB  - BACKGROUND: The value of surgery in multimodal treatment concepts of oral and
      oropharyngeal cancer, respecting quality of life and survival rates, should be
      evaluated. PATIENTS: Patients with oral or oropharyngeal cancer were grouped, if
      tumor-targeted surgery was part of a multimodal treatment concept or if the
      patients received radiotherapy with or without chemotherapy only. Surgical versus
      non-surgical therapy, age, disease extent, tumor site and comorbidity as measured
      by the American Society of Anesthesiologists (ASA) physical status score were
      included in a Cox proportional hazard analysis. Quality of life was assessed 3
      years following treatment employing the EORTC-C30 and H&N35 questionnaires.
      RESULTS: Patients treated with radiotherapy with or without chemotherapy only
      (63/140) had a worse survival (hazard ratio 1.7037, 95 % CI 0.9981 to 2.9080, p =
      0.0508) than patients treated with surgery (77/140) as a part of a multimodal
      treatment concept. Disease extent (p < 0.01) and ASA score (p < 0.01) had a
      significant impact on survival. Quality of life scores were remarkably similar in
      surgically and non-surgically treated patients. CONCLUSIONS: The results of this
      study indicate that surgery remains a core modality of oral and oropharyngeal
      cancer treatment. External beam radiotherapy only, also if applied in current
      fractionation techniques, may not be sufficient to achieve adequate results.

PMID- 18629756
TI  - [Do clinical symptoms and laryngoscopic findings of laryngo-pharyngeal reflux
      correlate?].
AB  - BACKGROUND: ENT specialists are often confronted with symptoms which are related
      to laryngo-pharyngeal reflux. The high prevalence, as well as therapy with PPIs
      (proton pump inhibitors) has recently raised controversies. Goal of our study was
      to survey laryngeal tissue irritation signs, as well as reflux associated
      complaints in a cohort of "healthy" men. Furthermore to describe if and to which
      grade subjective symptoms correlate with clinical signs. METHODS: We surveyed in
      a prospective, population based study cohort of 64 men the prevalence of
      laryngeal irritation signs with laryngoscopy (based on the Reflux Finding Score-
      RFS) and reflux associated complaints (Reflux Symptoms Index--RSI). RESULTS: A
      third of all volunteers had pathological values as assessed by the RSI
      questionnaire. Laryngoscopy revealed only in six men signs suspicious of LPR.
      Symptoms and laryngoscopic findings did not correlate. CONCLUSION: In most cases
      no clinical substrate could be identified in symptoms usually contributed to LPR.
      These are often non specific and a careful examination of other factors should be
      taken.

PMID- 18629757
TI  - [Variations of the anatomical position of the internal carotid artery as an
      important differential diagnosis of parapharyngeal tumors].
AB  - PATIENT: A case of a 78-year-old man with globus syndrome is reported who was
      referred to our department because of a tumor of the right parapharyngeal wall.
      Radiological and endoscopic examination revealed that the tumor was caused by an
      extracranial kinking of the right internal carotid artery. DISCUSSION: Variations
      of the anatomical position of the internal carotid artery in the parapharyngeal
      space are potentially at risk during routine ENT-procedures such as adenoidectomy
      and tonsillectomy or during endoscopic procedures with diagnostic biopsies. Data
      about the frequency of variations of the clinical course of the internal carotid
      artery dorsolateral of the lateral pharyngeal wall vary in literature from 4% to
      66%. By cost-effective ultrasound and duplex-ultrasound, computed-tomography,
      magnetic resonance imaging with angiography or by conventional angiography a wide
      variety of different diagnostic imaging methods is available. While coiling of
      the internal carotid artery is ascribed to embryological malformation, elongation
      and kinking of the artery are due to atherosclerosis or fibromuscular dysplasia.
      These variations are often asymptomatic but they can also cause symptoms from
      globus syndrome to cerebrovascular insufficiency producing ischemic attacks or
      infarction. This case report emphasizes the clinical importance of variations of
      the clinical course of the internal carotid artery as a differential diagnosis of
      parapharyngeal tumors since iatrogenic injuries during routine pharyngeal surgery
      with disastrous outcome were frequently reported in literature. Unexperienced ENT
      surgeons should be warned and experienced ENT-surgeons should be reminded of
      those dangerous variations.

PMID- 18629758
TI  - [Mycotic aneurysm of the internal carotid artery].
AB  - The detection of aneurysms of the internal carotid artery due to acute or chronic
      neck infections seems to be a rather rarely event. However, if aneurysms or
      pseudoaneurysms of the neck region occur, than mostly by bleeding complication or
      unclear significant soft tissue swelling. The case of a patient is reported, who
      underwent an abscess tonsillectomy. The intraoperative situation of the right
      tonsillar fossa was found to show suspicious pulsations under the scarred and
      inflamed peritonsillar tissue layer. The postoperative performed intraarterial
      angiography verified the diagnosis of the aneurysm of the internal carotid artery
      nearby the tonsillar fossa. The diagnosis mycotic aneurysm has been concluded by
      the long lasting tonsillitis history with one further peritonillar abscess in the
      past, intraoperative and histological signs of peritonsillitis and the the result
      of an intraarterial angiography carried through 10 years ago without any clue to
      aneurysm. A bleeding complication did not occur in this case. The patient went
      into the care of vascular surgeons with the indication to perform a stent
      application.

PMID- 18629759
TI  - A pedicled vascularized ulnar nerve graft based on the epineurial vascular
      supply: a case report.

PMID- 18629760
TI  - [Johann Friedrich Dieffenbach and his influence on the development of plastic
      surgery].

PMID- 18629761
TI  - [Glomangiomatosis on the hand. A case report].
AB  - Glomus tumours are solitary benign lesions most frequently located subungually on
      fingers and toes. In the rare case of a glomangiomatosis, the typical glomus
      cells are found on the altered vessel wall of the angiomatosis. Due to the rarity
      of this disease, no therapeutic golden standard has been mentioned in the
      literature, and a conservative treatment is usually adopted. The case of a 20
      year-old craftsman with congenital, painful glomangiomatosis on his left dominant
      hand, progressively limiting the functionality of this limb, is reported. Two
      years after unsuccessful partial tumour resection, a surgical treatment based on
      radical tumour resection in terms of a finger amputation was performed. The 1
      year follow-up showed no signs of pain for the patient.

PMID- 18629762
TI  - [Ossification in the carpal tunnel as a rare cause for untypical carpal tunnel
      syndrome].
AB  - There are typical causes for carpal tunnel syndromes as well as a series of rare
      causes. Furthermore, the clinical image can also be untypical. This report is
      about a 59-year-old female patient with an untypical clinical symptomatology and
      with a rare cause: there was no major pain during the night or in the morning, no
      paraesthesias and no impairment of the fine motor skills, nevertheless, there
      were rapid paraesthesias and pain in the first three fingers of the right hand
      immediately after hyperextension of the wrist. Although the discomforts had
      already existed for 2 years they were not recognised properly because they were
      untypical and incomplete and neurography was negative. 3 years later in a renewed
      examination X-ray pictures of the carpus were taken and a 4 x 6 x 8 mm big
      ossicle on the ground of the carpal canal was found, the computed tomography and
      the intraoperative situs confirmed the image. The histology gave the diagnosis of
      a loose osteochondral body. Postoperatively the patient was quickly was free of
      the symptoms.

PMID- 18629763
TI  - [Dermal subsitute with the collagen-elastin matrix Matriderm in burn injuries: a
      comprehensive review].
AB  - Matriderm is a dermal substitute consisting of a native (non-cross-linked)
      collagen matrix supplemented by a elastin hydrolysate. It is available in sheets
      of 1 mm and 2 mm thickness, and may be covered in a single step procedure with
      immediate split thickness skin grafting. Duration of the surgical procedures are
      only marginally increased. There is no diminished take of split thickness graft
      and only marginally prolonged healing time compared with the split thickness
      graft only. In experimental models the matrix reduces wound contracture,
      histologically collagen bundles in the scar are more randomly orientated.
      Clinical trials with a long-term clinical evaluation showed no difference in scar
      elasticity between the described dermal substitute and split thickness grafts
      alone. There is a lack of clinical data on the development of wound contracture.

PMID- 18629764
TI  - Colon patch esophagoplasty: an alternative to total esophagus replacement?
AB  - BACKGROUND: Resistant benign esophageal strictures (ES) are likely to require
      esophageal replacement. The use of colon patch esophagoplasty (CPE) was
      originally described for the correction of long segment esophageal stenosis,
      however it was thought that the length of the stricture would limit the use of
      the patch technique. We performed CPE on 3- to 4-inch strictures with a good
      outcome. AIM: We report here on our results of the use of CPE for long and short
      ES. PATIENTS AND METHODS: A retrospective study was carried out on patients
      operated for resistant ES using a vascularized colonic patch. The technique used
      was the same as described by Hecker and Hollmann with a few modifications. We
      used the right colon. Instead of passing the patch through the hiatus we placed
      it in the right pleural cavity through a small incision in the diaphragm. An
      appropriately sized patch was sewn to a generous longitudinal esophagotomy
      extending well beyond the stricture using running 4/0 polydiaxone sutures.
      RESULTS: Four patients underwent CPE, three because of an extensive caustic
      stricture and one with a stricture after failed atresia repair. All four patients
      were males. They were almost the same age except for the one with post
      tracheoesophageal fistula (TEF) repair stricture. The site of the stricture was
      the mid esophagus in three and the lower esophagus in one. Three patients had an
      anastomatic leak which was treated conservatively and one patient required a
      postoperative fundoplication 10 days post-CPE to stop the leak. The first patient
      developed a patch diverticulum, which was resected 12 years after CPE. All had
      fundoplication pre-, intra- or post-CPE. The follow-up period ranged from 4 - 20
      years. All patients are eating and growing normally after surgery. No malignant
      changes were seen in the older patient. CONCLUSIONS: The length of the stricture
      is not a problem in CPE. Our results are encouraging on the use of CPE as an
      alternative to esophageal replacement. We suggest using CPE even for an entire
      scarred esophagus. A postoperative leak due to a long suture line can be overcome
      by fundoplication and supportive therapy.

PMID- 18629765
TI  - Epidermal growth factor in neonatal saliva.
AB  - AIMS OF STUDY: Epidermal growth factor (EGF) is an amino acid polypeptide that
      has been shown to promote mucosal healing and intestinal growth in experimental
      models and has a potential role in the aetiology and treatment of NEC. The aim of
      this study was to determine the normal levels of salivary EGF in a cohort of
      healthy neonatal infants. MATERIAL AND METHODS: With appropriate ethical approval
      and informed consent, saliva was collected using a suction catheter from all
      normal neonatal infants admitted to our unit over a 9-month period. The samples
      were immediately frozen at - 20 degrees C and analysed using an ELISA assay (R &
      D Systems, Oxford, UK). Samples taken a week prior to and two weeks following a
      septic episode (as diagnosed by clinical or biochemical evidence) were excluded.
      Patients with congenital malformations and chromosomal anomalies were excluded.
      RESULTS: A total of 65 samples were collected and analysed from 27 babies. The
      mean gestation and weight of the patients was 32.2 (+/- 5.50) weeks and 1954.44
      (+/- 1045.7) grams, respectively. Five samples from 2 infants were discarded.
      None of the patients in whom the samples were analysed had clinical or serum
      markers of sepsis or NEC. All infants were given maternal breast milk starting at
      the mean age of 5 (+/- 3.47) days. The mean EGF values were 676.95 (+/- 168.47)
      pg/ml. There was a significant rise in serial salivary EGF values in patients (p
      = 0.0019). There was no correlation between the EGF values and gestation (R =
      0.35, p = 0.08). The birth weight, sex or timing of initiating enteral feeds did
      not correlate with EGF values. CONCLUSION: In conclusion, our study shows a rise
      in salivary EGF values in serial samples in a clearly defined group of healthy
      infants.

PMID- 18629766
TI  - Multiple surgical interventions due to recurrent intussusception in a patient
      with henoch-schonlein purpura: a case report.
AB  - Gastrointestinal (GI) symptoms in Henoch-Schonlein purpura (HSP) are common and
      occur in about two-thirds of patients. Surgical complications, while uncommon,
      are potentially severe. The preoperative diagnosis is based mainly on a high
      index of suspicion leading to imaging studies that may include abdominal
      sonography. We describe here the first case of a patient who developed recurrent
      intussusception attributed to HSP that led to repeated surgical interventions.

PMID- 18629767
TI  - Rare gallbladder parasitosis mimicking cholelithiasis: Dicrocoelium dendriticum.
AB  - Cholelithiasis is increasingly diagnosed in childhood and infancy. Biliary
      parasites are the rarest cause of cholelithiasis in all age groups. We present a
      twelve-year-old girl with non-hemolytic gallbladder stone and discuss the
      clinical features and differential diagnosis of Dicrocoelium dendriticum (DD)
      invasion that causes and/or mimics cholelithiasis in children.

PMID- 18629768
TI  - Hepatic haemangioendothelioma: a vertical association with biliary atresia?
AB  - Haemangioendotheliomas (HAE) are the commonest vascular tumours of the liver in
      infancy and are characterised by solitary or multifocal lesions often arising in
      conjunction with cutaneous haemangiomas. The authors report on a 4-month-old
      infant with massive hepatomegaly and hypothyroidism due to multifocal HAE whose
      mother had been born with biliary atresia. As the incidence of biliary atresia in
      the UK is about 1 in 16 000 live births, the association reported here seems more
      than co-incidental. This report reviews the literature and discusses potential
      aetiologies to explain this rare association.

PMID- 18629769
TI  - Jarcho-Levin syndrome presenting with diaphragmatic hernia.
AB  - Jarcho-Levin syndrome (spondylothoracic or spondylocostal dysostosis) is an
      eponym that is used to define individuals with a short neck, short trunk, and
      short stature and multiple vertebral anomalies. The prognosis is directly related
      to respiratory complications. Reported findings associated with Jarcho-Levin
      syndrome include congenital heart defects, abdominal wall malformations,
      genitourinary malformations, upper limb anomalies, and neural tube defects. We
      report on a 6-day-old girl who presented with an incomplete form of Jarcho-Levin
      syndrome with late-presenting congenital diaphragmatic hernia and congenital
      heart disease.

PMID- 18629770
TI  - Thoracoscopic plication for diaphragmatic eventration in a 3-month-old infant.
AB  - A 3-month-old male presented with a 2-month history of intermittent shortness of
      breath with chest retractions and wheezing which worsened with feeding. The
      patient was diagnosed with bronchiolitis during one of several hospital
      admissions and treated with bronchodilators without success. On the third
      hospitalization, the patient was diagnosed with right-sided diaphragmatic
      eventration. Surgical intervention consisted of video-assisted thoracoscopic
      surgery (VATS) with plication of the right diaphragm. The patient was discharged
      on the 2nd postoperative day. At the clinical visit 2 weeks postoperatively, the
      patient's respiratory symptoms as well as interrupted feeding secondary to
      shortness of breath had resolved. The chest X-ray revealed a significant
      improvement in the position of the right diaphragm. VATS with diaphragmatic
      plication is a viable approach for treating diaphragmatic eventration during
      infancy. To our knowledge, this 3-month-old male is the youngest patient reported
      to have undergone plication via VATS for diaphragmatic eventration.

PMID- 18629771
TI  - Consecutive bilateral proximal tibial fractures after minor sports trauma.
AB  - INTRODUCTION: Fractures of the proximal tibia are infrequent during childhood and
      adolescence. However, intra-articular fractures, growth plate separations and
      metaphyseal fractures do appear. CASE REPORT: An obese adolescent male suffered
      from consecutive bilateral fractures of the tibia within 6 months of each after
      minor sports trauma. On the left side, the injury presented as a epiphyseal
      separation of the Salter-Harris I type; on the right side, as a transitional two
      plane fracture. Both injuries were treated by percutaneous screwing and healed
      without any signs of posttraumatic growth disorder. DISCUSSION: Although proximal
      tibial injuries are rare, they frequently seem to appear bilaterally after
      inadequate trauma. A causal connection to morphological changes prior to physeal
      closure can be assumed.

PMID- 18629772
TI  - Severe blue rubber bleb nevus syndrome in a neonate.
AB  - We report on a child with blue rubber bleb nevus syndrome (BRBNS) presenting
      during the first days of life with severe bleeding from the upper
      gastrointestinal tract. Medical treatment with methylprednisolone, cyklokapron,
      interferon 1 alpha and numerous blood transfusions were given to control bleeding
      during the first 3 years of life. Afterwards repeated endoscopic
      electrocoagulation were performed over a period of one year resulting in a
      termination of bleeding episodes. At ten years of age the patient developed
      spastic diplegia with slight walking disabilities, coordination and fine motor
      problems. The case is unique because 1) it is the first neonatal case with BRBNS
      and severe gastrointestinal bleeding; 2) the patient was successfully treated by
      endoscopic electrocoagulation; and 3) the long-term follow-up. The use of
      electrocoagulation appears to have been effective and ablation of the stomach
      could be avoided until now.

PMID- 18629773
TI  - Congenital apocrine tumour: a rare scalp tumour.
AB  - We report a rare congenital scalp tumour with histological diagnosis of a
      congenital apocrine adenoma with features of a tubular adenoma. Following cranial
      CT and MRI, the tumour was serially excised. The macroscopic and microscopic
      appearances and management are discussed. To our knowledge, such a case has not
      been previously reported.

PMID- 18629774
TI  - An unusual midline swelling--case report of a cutaneous bronchogenic cyst.
AB  - Cutaneous bronchogenic cyst remains a very rare cause of a midline swelling in
      children. The authors report a case of a 14-month-old boy who presented with a
      sternal sinus and consequent abscess. Histopathological analysis revealed this to
      be a cutaneous bronchogenic cyst. This is a very rare lesion with only 65 cases
      reported in the literature. It is caused by an abnormal development in the distal
      tracheobronchial tree, and diagnosis is confirmed by ciliated and mucin-producing
      pseudostratified columnar epithelium of respiratory type on histopathological
      analysis. It is managed by resection of the cyst, as these cysts are often foci
      for subsequent infections and malignant potential has been reported.

PMID- 18629775
TI  - Iatrogenic anterior diaphragmatic hernia in childhood.
AB  - Congenital anterior diaphragmatic hernias (ADH) account for 2 - 6 % of
      diaphragmatic defects, whereas acquired ADH are rare. These hernias are most
      often the result of blunt or penetrating trauma. This is the first report of
      iatrogenic ADH in childhood. Two children with asymptomatic, iatrogenic ADH were
      diagnosed at 6 and 12 months of age, respectively. Both had undergone previous
      cardiac surgery requiring pericardial drainage. The ADH was seen on an incidental
      chest X-ray in one patient, and during a laparoscopic-assisted gastrostomy in the
      other. Both were successfully repaired laparoscopically. Subxiphoid pericardial
      drains may result in iatrogenic ADH. A high index of suspicion after cardiac
      surgery is necessary to avoid missing this potentially serious complication.
      Laparoscopy is a useful tool in both the diagnosis and repair of this condition.

PMID- 18629776
TI  - Morgagni hernia repair in a small child using da Vinci robotic instruments--a
      case report.
AB  - BACKGROUND: The recently introduced use of robotic surgery in minimally invasive
      surgery procedures facilitates several steps in the operative procedure. We
      report the first case of a robot-assisted laparoscopic repair of a Morgagni
      hernia using the da Vinci Surgical System from Intuitive Surgical (Sunnyvale, CA,
      USA) in a 7.8 kg 18-month-old child. METHODS: Four trocars were used to gain
      access to the abdomen. The robot-enhanced instruments were used to close the
      hernia defect with interrupted, absorbable sutures, using intracorporeal knot
      tying. RESULTS: The operation was completed laparoscopically without a patch. The
      total setup time for the robotic system was 35 minutes including draping. The
      operating time at the robotic console was 80 minutes. The child tolerated an oral
      intake the day after surgery and was discharged home on the third postoperative
      day. CONCLUSION: Robot-assisted laparoscopic Morgagni hernia repair is feasible
      in small children.

PMID- 18629777
TI  - Editor's comments: the role of inflammation in the development and progression of
      cancer.

PMID- 18629778
TI  - Parallel assessment of circulatory cell-free DNA by PCR and nucleosomes by ELISA
      in breast tumors.
AB  - OBJECTIVES: In order to assess the potential biomolecules for breast cancer, we
      analyzed in parallel the levels of cell-free glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) and cell-free nucleosomes in serum samples from patients
      with benign and malignant breast tumors. The levels of cell-free DNA obtained by
      quantitative PCR were compared with those obtained by enzyme-linked immunosorbent
      assay (ELISA). METHODS: Twenty-three patients with benign breast tumors, 27
      patients with breast cancer, and 32 age-matched healthy women were recruited. The
      amounts of serum nucleosomes were analyzed by ELISA and the levels of cell-free
      GAPDH were measured by real-time quantitative PCR. The correlation between
      nucleosome and cell-free GAPDH levels was examined using the Spearman rank test.
      RESULTS: The levels of cell-free GAPDH were significantly higher in the serum
      samples of patients with benign and malignant breast tumors than in those of the
      control group (median 37,966 GE/mL, range 3,802-130,104 versus 11,770 GE/mL,
      range 2,198-73,522, p=0.035 and median 40,698 GE/mL, range 3,644-192,482 versus
      11,770 GE/mL range 2,198-73,522, p=0.001). The concentration of cell-free GAPDH
      correlated significantly with the quantities of nucleosomes in serum samples
      (r=0.451, p=0.000). There was, however, no significant difference between healthy
      individuals and women with benign breast tumors or breast cancer in terms of
      nucleosomes determined by ELISA. CONCLUSION: Our data suggest that the cell-free
      serum GAPDH DNA assayed by quantitative PCR is a better biomarker than
      nucleosomes assayed by ELISA in patients with breast tumors.

PMID- 18629779
TI  - Measurement of mRNA of 11 biomarkers by RT-PCR to detect lymph node involvement
      in cervical cancer.
AB  - Lymph node metastases are a major prognostic factor in cervical carcinomas. The
      aim of this study was to characterize the expression of 11 markers in cervical
      tumors and negative lymph nodes and to determine which ones could be helpful for
      improving the specificity of molecular diagnosis of nodal involvement. Using
      TaqMan RT-PCR, we studied the expression of CK19, MUC1, HER1-HER4, VEGF, VEGF-C,
      uPA, MMP9, and PRAD1 in uterine cervical tumors and in histologically
      nonmetastatic lymph nodes of 8 patients diagnosed with locally advanced cervical
      cancer. We observed that CK19, MUC1, HER1-HER3, uPA, and VEGF had a significantly
      higher expression in cervical tumors than in the negative nodes, whereas VEGF-C
      expression level was higher in the negative nodes than in the tumors. PRAD1
      harbored similar expression levels in the tumors and in the negative nodes.
      Interestingly, 1 of the 4 patients who presented a clinical recurrence, showed
      elevated HER1, HER2, uPA, and VEGF in the histologically negative nodes. Our
      results suggest that CK19, MUC1, HER1-3, uPA, and VEGF are biomarkers that have a
      higher expression in tumoral cervical tissues compared with the negative lymph
      nodes and could be useful to diagnose nodal involvement in uterine cervical
      carcinoma. Our results should encourage us in continue to investigate a greater
      number of patients, including patients with histologically involved nodes.

PMID- 18629780
TI  - Expression of Mina53 and its significance in gastric carcinoma.
AB  - AIM: To study the expression of Mina53 and its relationships with
      clinicopathological characteristics, antioncogene inactivation and tumor
      proliferation in human gastric carcinoma, and to explore the role of Mina53 in
      carcinogenesis and tumor progression. METHODS: Expression of Mina53 and
      proliferating cell nuclear antigen (PCNA) was determined in gastric carcinoma
      (n=79), gastric dysplasia (n=21) and normal gastric tissues (n=20), while p53 was
      measured in gastric carcinoma tissues by immunohistochemistry. RESULTS: Mina53
      was negatively expressed in all normal mucosa tissues. Dysplasia specimens showed
      weakly positive staining for Mina53 in 3 of 21 cases. Elevated expression of
      Mina53 was observed in 72 (91.1%) of the gastric carcinomas. No significant
      associations were found between Mina53 and clinicopathological characteristics
      such as sex, age, histological differentiation, distant metastasis and lymph node
      metastasis (p>0.05). There was a significant association with depth of invasion
      (X2=5.385, p<0.05) and TMN stage (X2=6.255, p<0.05). In gastric carcinoma,
      positive staining for p53 was detected in 53 of 79 cases (67.1%), showing a
      significant association with Mina53 (X2=5.161, p<0.05). The mean (+/- SD) PCNA
      labeling index for gastric carcinoma was 39.47+/-16.92%. Mina53 expression was
      positively associated with PCNA level (r=0.756, p<0.01). CONCLUSION: Mina53 was
      overexpressed in gastric carcinoma and associated with tumor proliferation and
      antioncogene inactivation. Mina53 could therefore play an important role in the
      carcinogenesis and progression of gastric carcinoma.

PMID- 18629781
TI  - Immunohistochemical expression of p53 and Ki67 in colorectal adenomas and
      prediction of malignancy and development of new polyps.
AB  - The aim of this study was to investigate the immunohistochemical expression of
      p53 and Ki67 in colorectal adenomas in order to clarify their significance as
      indicators of malignancy and development of new polyps. Seventy-eight polyps were
      removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas
      with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and
      22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at
      3-year follow-up). We tested the association between p53 and Ki67 expression and
      various clinicopathological variables, and regression analysis was performed to
      identify the risk factors for malignancy and development of new adenomas. A
      significant correlation between the grade of atypia and p53 immunoreactivity was
      observed. Ki67 expression was not related to atypia and no correlation was found
      between p53 and Ki67 immunoreactivity. Regression analysis showed that size
      (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to
      malignant transformation, whereas the number of synchronous primary polyps
      emerged as the only predictive factor of development of new adenomas, although
      without statistical significance. The expression of biological markers may be in
      future added to the currently examined features of polyps; however, further
      studies are needed to better define their predictive value.

PMID- 18629782
TI  - Gastrointestinal stromal tumors (GISTs): from science to targeted therapy.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. GISTs represent a distinct category of tumors
      characterized by oncogenic mutations of the KIT receptor tyrosine kinase in a
      majority of patients. KIT is useful not only for the diagnosis but also for
      targeted therapy of this disease. Imatinib, a tyrosine kinase inhibitor, is
      widely used in advanced and metastatic GISTs. This agent revolutionized the
      treatment strategy of advanced disease and is being tested in the neoadjuvant and
      adjuvant settings with encouraging results. New therapeutic agents like sunitinib
      have now been approved, enriching the treatment scenario for imatinib-resistant
      GISTs. The present review reports on the peculiar characteristics of this disease
      through its biology and molecular patterns, focusing on the predictive value of
      KIT mutations and their correlation with clinical outcome as well as on the
      activity of and resistance to approved targeted drugs.

PMID- 18629783
TI  - Brain irradiation-induced lymphocytosis predicts response in cancer patients with
      brain metastases.
AB  - Lymphocytopenia is one of the main toxicities of radiotherapy and its severity is
      related to the irradiation dose. The occurrence of lymphocytopenia depends on the
      body site of radiotherapy; it is most pronounced with pelvic irradiation, whereas
      the effect of brain irradiation on the lymphocyte count is to be elucidated. This
      preliminary study was performed to evaluate changes in lymphocyte number
      occurring during brain irradiation in cancer patients with brain metastases. The
      study included 50 patients who received brain radiotherapy for single or multiple
      brain metastases at a total dose of 30 Gy. Overall, no significant changes in
      mean lymphocyte number occurred during brain radiotherapy. However, when
      lymphocyte variations were assessed in relation to the clinical response of brain
      metastases, a significant increase in the mean number of lymphocytes was found in
      patients who achieved objective regression of brain metastases on brain
      irradiation. The mean lymphocyte number decreased in nonresponding patients,
      albeit without a statistically significant difference with respect to the
      pretreatment values. The results of this study show that the efficacy of
      radiotherapy in the treatment of brain metastases is associated with a
      significant increase in mean lymphocyte number. Therefore, evidence of brain
      irradiation-induced lymphocytosis may predict the efficacy of radiotherapy.

PMID- 18629784
TI  - Protein biochip array of adhesion molecule expression in peripheral blood of
      patients with nasal polyposis.
AB  - Nasal polyposis is a chronic non-infectious inflammatory disease of the nasal and
      paranasal cavity mucosa of unknown multifactorial origin in which inflammatory
      cells, and in particular eosinophils, seem to play a pivotal role. Eosinophil
      migration from the bloodstream to nasal polyps is considered to be specific and
      is a complex process involving several different molecules such as ICAM-1, VCAM
      1, and L-, P- and E-selectins. The aim of this study was to investigate, using a
      protein biochip array technology, the concentrations of these molecules in the
      peripheral blood of a group of patients affected by nasal polyposis. Patients
      exhibited a significantly higher expression of VCAM-1, E-selectin, and L-selectin
      compared to healthy controls, and Spearman's rank correlation test limited to the
      molecules with significant betweengroup differences demonstrated a significant
      correlation between VCAM-1 and E-selectin, VCAM-1 and L-selectin, and Eselectin
      and L-selectin. The results of this investigation are in line with those coming
      from various imunohistochemical analyses, and seem to confirm the role of
      inflammation in the pathogenesis of nasal polyposis. These molecules may also
      represent novel therapeutic targets in the treatment of nasal polyps, and may
      allow the selection of pharmacological prophylactics that would allow effective
      inhibition of the inflammation induced by a given allergen.

PMID- 18629785
TI  - Correlation between soluble IL-2 receptor serum levels and regulatory T
      lymphocytes in patients with solid tumors.

PMID- 18629786
TI  - Poor usage of HUGO standard gene nomenclature in cancer marker studies.

PMID- 18629787
TI  - Lack of association between skewing of X-chromosome inactivation in blood cells
      and colorectal cancer.

PMID- 18629788
TI  - Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as
      complementary markers.
AB  - The biochemical activity of medullary thyroid carcinoma (MTC) includes production
      of calcitonin (CT), chromogranin A (CgA) and carcinoembryonic antigen (CEA).
      Routine CT measurement has been proposed as part of the initial evaluation of
      thyroid nodules and its use could ultimately decrease the morbidity and mortality
      of MTC. We report on a 43-year-old female patient with a large MTC expressing CT,
      CgA and CEA on immunostains but with negative preoperative CT and CgA results.
      Serum CEA was slightly increased and its rapid disappearance predicted radical
      cure by surgery as confirmed by 2-year follow-up. Our report illustrates that a
      diagnosis of MTC cannot always be excluded by negative preoperative CT. Fine
      needle aspiration with cytomorphological analysis and complementary
      immunocytochemistry remains an essential diagnostic tool. Finally, serum aliquots
      must be stored before thyroid surgery in order to measure circulating forms of
      complementary markers found by tissue immunostaining (CEA and CgA).

PMID- 18629790
TI  - Factors affecting cellulose hydrolysis and the potential of enzyme recycle to
      enhance the efficiency of an integrated wood to ethanol process.
AB  - Past technoeconomic modeling work has identified the relatively large
      contribution that enzymatic hydrolysis adds to the total cost of producing
      ethanol from lignocellulosic substrates. This cost was primarily due to the high
      concentration of enzyme and long incubation time that was required to obtain
      complete hydrolysis. Although enzyme and substrate concentration and end-product
      inhibition influenced the rate of hydrolysis, the effect was less pronounced
      during the initial stages of hydrolysis. During this time most of the cellulases
      were adsorbed onto the unhydrolyzed residue. By recycling the cellulases adsorbed
      to the residual substrate remaining after an initial 24 h, a high rate of
      hydrolysis, with low overall residence time and minimal cellulase input, could be
      achieved for several rounds of enzyme recycle. A comparison of the front end
      (pretreatment, fractionation, and hydrolysis) of a softwood/hardwood to ethanol
      process indicated that the lignin associated with the softwood-derived cellulose
      stream limited the number of times the cellulose containing residue could be
      recycled. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629791
TI  - Effects of kinetics of adsorption and coalescence on continuous foam
      concentration of proteins: Comparison of experimental results with model
      predictions.
AB  - Protein enrichment and recovery were measured in a continuous foam concentration
      column for bovine serum albumin (BSA) for different pool heights, foam heights,
      superficial gas velocities, bubble sizes, feed flow rates, pH, and ionic
      strengths. Protein enrichment was found to decrease with an increase in pool
      height for low pool heights, reach a minimum at an intermediate pool height, and
      subsequently increase with pool height for sufficiently large pool heights
      eventually approaching an asymptotic value. Such a behavior was due to the
      combined effects of kinetics of adsorption of protein and coalescence. The
      increase in protein enrichment with pool height was due to the predominant effect
      of kinetics of adsorption of protein, whereas the opposite behavior at low pool
      heights was due to the predominant effect of coalescence in the foam. Protein
      enrichment was found to be higher for smaller feed concentrations, smaller gas
      velocities, larger bubble sizes, and larger foam heights. Enrichment at pH values
      different from the isoelectric point was found to be higher because of more
      coalescence. A model for foam concentration of proteins was employed to predict
      enrichment and recovery. The model predictions agreed well with the experimental
      data. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629792
TI  - Sparging and agitation-induced injury of cultured animals cells: Do cell-to
      bubble interactions in the bulk liquid injure cells?
AB  - It has been established that the forces resulting from bubbles rupturing at the
      free air (gas)/liquid surface injure animal cells in agitated and/or sparged
      bioreactors. Although it has been suggested that bubble coalescence and breakup
      within agitated and sparged bioreactors (i.e., away from the free liquid surface)
      can be a source of cell injury as well, the evidence has been indirect. We have
      carried out experiments to examine this issue. The free air/liquid surface in a
      sparged and agitated bioractor was eliminated by completely filling the 2-L
      reactor and allowing sparged bubbles to escape through an outlet tube. Two
      identical bioreactors were run in parallel to make comparisons between cultures
      that were oxygenated via direct air sparging and the control culture in which
      silicone tubing was used for bubble-free oxygenation. Thus, cell damage from cell
      to-bubble interactions due to processes (bubble coalescence and breakup)
      occurring in the bulk liquid could be isolated by eliminating damage due to
      bubbles rupturing at the free air/liquid surface of the bioreactor. We found that
      Chinese hamster ovary (CHO) cells grown in medium that does not contain shear
      protecting additives can be agitated at rates up to 600 rpm without being damaged
      extensively by cell-to bubble interactions in the bulk of the bioreactor. We
      verified this using both batch and high-density perfusion cultures. We tested two
      impeller designs (pitched blade and Rushton) and found them not to affect cell
      damage under similar operational conditions. Sparger location (above vs. below
      the impeller) had no effect on cell damage at higher agitation rates but may
      affect the injury process at lower agitation intensities (here, below 250 rpm).
      In the absence of a headspace, we found less cell damage at higher agitation
      intensities (400 and 600 rpm), and we suggest that this nonintuitive finding
      derives from the important effect of bubble size and foam stability on the cell
      damage process. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629793
TI  - Thermal stability studies of a globular protein in aqueous poly(ethylene glycol)
      by (1)H NMR.
AB  - The reversible folding destabilization of hen lysozyme has been confirmed by a
      melting temperature (T(m)) decrease in aqueous poly(ethylene glycol) (PEG). The
      percent denatured, extracted from the histidine 15 C2H (H15 C2H) native and
      denatured peak areas from 500-MHz one-dimensional proton nuclear magnetic
      resonance (1D (1)H NMR) spectra in D(2)O, was analyzed through denaturation
      temperatures at 0% and 20% (w/w) PEG 1000. The lysozyme (3.5 mM) T(m) decreased
      by 4.2 degrees C and 7.1 degrees C in 20% (w/w) PEG 1000 at pH 3.8 and 3.0,
      respectively. The T(m) decreased with increasing lysozyme concentration.
      Additionally, the temperature-induced resonance migrations of 17 protons from 8
      residues indicate that the native lysozyme structure undergoes temperature
      induced conformational changes. The changes were essentially identical in both 0%
      and 20% (w/w) PEG 1000 at both pH 3.0 and 3.8. This small, local restructuring of
      the hydrophobic box region may be a manifestation of temperature-dependent
      solution hydrophobicity, whereas active-site cleft fluctuations may be due to the
      inherent active-site flexibility. The lysozyme structure in PEG at 35 degrees C
      was determined to be essentially native from the (1)H nuclear Overhauser effect
      spectroscopy (NOESY) fingerprint regions. Additionally, lysozyme chemical shifts,
      from 1D spectra, in PEG 200, 300, and 1000 at 35 degrees C and various
      concentrations were essentially identical, further confirming that the
      conformation remains native in various PEG solutions. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18629794
TI  - Production of tissue plasminogen activator (tPA) in two and three dimensionally
      growing cultures of Bowes melanoma cells.
AB  - Bowes melanoma cells synthesize more tissue plasminogen activator (tPA) in
      monolayer cultures than in multicell spheroids. Cellular production of tPA in
      these cells was measured during a cultivation period of 800 h. Without changing
      the cell culture assay, we were able to obtain monolayers, multilayers, and
      multicell spheroids (cell aggregates) by stirring microcarrier beads in 500-mL
      spinner flasks operated at 50 rpm. Thus, the medium conditions in the liquid were
      similar for cells in monolayers and in multicell spheroids. Probes for
      measurements of intracellular and extracellular parameters were taken from the
      same culture at distinct times; therefore, their variations during cultivation
      can directly be compared. Because cells were cultured in an unregulated (with
      regard to pH, glucose, etc.) spinner flask, their concentration was kept below
      10(6) cells/mL, thus avoiding too fast and too severe depletion of oxygen and
      other medium factors. Nevertheless, the tPA productivity decreased from 8
      ng/h/10(6) cells (monolayer) to 4 ng/h/10(6) cells (multicell spheroids with
      microcarrier nucleus, 800 mum diameter), matching the decrease of total cellular
      protein. Due to medium depletion, the cell cycle distribution changed from 45% to
      68% G(1) cells in a characteristic way during growth of multicell spheroids. This
      is accompanied by changes in amino acids, glucose, lactate, and pH, which may
      account for the reduction of tPA productivity. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629795
TI  - Modulation of the phosphate-starvation response in Escherichia coli by genetic
      manipulation of the polyphosphate pathways.
AB  - The effect of intracellular polyphosphate on the phosphate-starvation response in
      Escherichia coli was studied by genetically manipulating the intracellular
      polyphosphate levels and by performing phosphate shifts on the genetically
      engineered strains. Strains that produced large quantities of polyphosphate and
      were able to degrade it induced the phosphate-starvation response to a lesser
      extent than wild-type strains, whereas strains that were unable to degrade a
      large intracellular polyphosphate pool induced the phosphate-starvation response
      to a greater extent than wild-type strains. These results have important
      implications for expression of heterologous genes under control of the phoA
      promoter. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629796
TI  - Continuous detoxification, transformation, and degradation of nitrophenols in
      upflow anaerobic sludge blanket (UASB) reactors.
AB  - The anaerobic transformation and degradation of nitrophenols by granular sludge
      was investigated in upflow anaerobic sludge blanket (UASB) reactors continuously
      fed with a volatile fatty acid (VFA) mixture as the primary substrate. During the
      start-up, subtoxic concentrations of 2-nitrophenol (2-NP), 4-nitrophenol (4-NP),
      and 2, 4-dinitrophenol (2, 4-DNP) were utilized. 4-NP and 2, 4-DNP were readily
      converted to the corresponding aromatic amine; whereas 2-NP was converted to
      nonaromatic products via intermediate formation of 2-aminophenol (2-AP). These
      conversions led to a dramatic detoxification of the mononitrophenols because the
      reactors treated the nitrophenolics at the concentrations which were over 25
      times higher than those that caused severe inhibition. VFA removal efficiencies
      greater than 99% were achieved in both reactors at loading rates greater than
      11.4 g COD per liter of reactor volume per day even at volumetric loading of
      mononitrophenols up to 910 mg/L . d.The sludges obtained from each of the
      reactors at the end of the continuous experiments were assayed for their specific
      nitrophenol reducing activity in the presence of different primary substrates.
      Reduction rates of 45 and 26 mg/g volatile suspended solids per day were observed
      for 2-NP and 4-NP, respectively, when utilizing the VFA mixture as primary
      substrate. Hydrogen, an interspecies-reduced compound, and substrates that
      provide interspecies-reducing equivalents-such as butyrate, propionate, and
      ethanol stimulated nitrophenol reduction, whereas acetate and methanol did not.
      Anaerobic batch biodegradability tests with the 2-NP-adapted sludge revealed that
      its corresponding aromatic amine, 2-AP, was degraded to methane at a specific
      rate of 14.5 mg/g VSS . d. Acetate was observed to be the major intermediate
      during 2-AP degradation in the presence of a specific methanogenic inhibitor 2
      bromoethanesulfonate. The results of this study indicate that UASB reactors can
      be applied to rapidly detoxify and, under certain circumstances, degrade
      nitroaromatic compounds. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629797
TI  - Covalent binding of a nerve agent hydrolyzing enzyme within polyurethane foams.
AB  - A phosphotriesterase preparation, extracted from Escherichia coli DH5alpha cells,
      was immobilized within a polyurethane foam matrix during polymer synthesis. The
      enzyme-foam interaction was shown to be covalent and analysis of the hydrolysis
      of paraoxon in aqueous solution demonstrated that more than 50% of the initial
      enzyme specific activity was retained after immobilization in the foam. Factors
      affecting the rate of paraoxon degradation include foam hydrophobicity, the
      degree of mixing applied to initiate polymerization, and foam pretreatment prior
      to use in substrate hydrolysis. The storage stability of the foam is significant,
      with phosphotriesterase-foam activity profiles exhibiting a three month half
      life. Foams are currently being developed for biocatalytic air filtering, in
      which gaseous substrates will be simultaneously adsorbed and degraded by the
      immobilized enzyme system. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629798
TI  - Effect of high shear on proteins.
AB  - Shear is present in almost all bioprocesses and high shear is associated with
      processes involving agitation and emulsification. The purpose of this study is to
      investigate the effect of high shear and high shear rate on proteins. Two
      concentric cylinder-based shear systems were used. One was a closed concentric
      cylinder shear device (CCSD) and the other was a homogenizer with a rotor/stator
      assembly. Mathematical modeling of these systems allowed calculation of the shear
      rate and shear. The CCSD generated low shear rates (a few hundred s(-1)), whereas
      the homogenizer could generate very high shear rates (> 10(5) s(-1)). High shear
      could be achieved in both systems by increasing the processing time. Recombinant
      human growth hormone (rhGH) and recombinant human deoxyribonuclease (rhDNase)
      were used as the model proteins in this study. It was found that neither high
      shear nor high shear rate had a significant effect on protein aggregation.
      However, a lower melting temperature and enthalpy were detected for highly
      sheared rhGH by using scanning microcalorimetry, presumably due to some changes
      in protein's conformation. Also, SDS-PAGE indicated the presence of low molecular
      weight fragments, suggesting that peptide bond breakage occurred due to high
      shear. rhDNase was relatively more stable than rhGH under high shear. No
      conformational changes and protein fragments were observed. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18629799
TI  - Noninvasive oxygen measurements and mass transfer considerations in tissue
      culture flasks.
AB  - Murine hybridomas were cultivated in tissue culture flasks. Dissolved oxygen
      tensions in the gas and liquid phases during cell growth were monitored. Oxygen
      levels were measured noninvasively by interrogating an oxygen-sensitive patch
      mounted on the interior surface of the tissue culture flask with an optrode from
      outside the tissue culture flask. Readings were made in tissue culture flasks
      with caps both cracked open and completely closed. Although the oxygen in the gas
      phase remained near atmospheric oxygen levels in both flasks, over time the
      liquid-phase oxygen tension at the bottom of the flasks reached zero during cell
      growth in both the open and closed tissue culture flasks. These results suggest
      that the widespread practice of cracking open tissue culture flask caps during
      cell growth with a view to supplying adequate oxygen to cells is ineffective and
      probably unnecessary.The mass transfer characteristics of the tissue culture
      flask were also studied. The dominant resistance to oxygen mass transfer to the
      sensor and the cells was through the liquid media. The mass transfer rates
      through the liquid layer under standard laboratory conditions were found to be
      greater than those predicted by diffusion alone. This suggests that mixing at a
      microscale occurs. Volumetric and specific oxygen consumption rates were also
      calculated from the sensor data. These consumption rates were comparable with
      values published elsewhere. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629800
TI  - Decreased chimeric antibody productivity of KR12H-1 transfectoma during long-term
      culture results from decreased antibody gene copy number.
AB  - The stability of KR12H-1 transfectoma in regard to chimeric antibody production
      was examined during long-term, repeated batch culture without selection pressure
      using antibiotics. Both serum-supplemented and serum-free media were used.
      Regardless of the medium used, the specific antibody productivity (q(Ab)) of
      transfectoma decreased by 60% to 88% during 70-day culture. This loss of antibody
      productivity was not due mainly to the appearance of a nonproducing population
      (NP) of transfectoma. The percentage of a producing population (P), which was
      monitored by the limiting dilution method, remained over 90% until the end of
      culture, indicating that the q(Ab) of P decreased during the culture. Flow
      cytometric data also showed the increase of cell population with low fluorescence
      intensity during culture, indicating that the intracellular antibody content of P
      decreased. The subclones of P obtained at the end of long-term culture were
      further characterized. Compared with the q(Ab) of P at the beginning of long-term
      culture, the q(Ab) of most P subclones was significantly low, confirming that the
      loss of antibody productivity was due mainly to the decreased q(Ab) of P during
      long-term culture. The decreased antibody gene copy number of P subclones was
      found to be partly responsible for the decreased q(Ab) of P during long-term
      culture. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629801
TI  - Production of phosphomonoesterases by Nicotiana tabacum 1507 in an aqueous two
      phase system.
AB  - Studies were conducted on Nicotiana tabacum 1507 cultivation in an aqueous two
      phase system (PD(5)) formed by adding 4% PEG (MW 20,000) and 7.5% dextran (MW
      70,000) to the medium. The time course of growth and changes in the phase volumes
      of the PD(5) system, as well as the biosynthesis, secretion, and partitioning of
      phosphomonoesterases during 11 days of cultivation, were followed. In comparison
      with N. tabacum 1507 cultivation as a free suspension, on day 8 of cultivation in
      the PD(5) system the yields of acid and alkaline extracellular
      phosphomonoesterases were 18 and 10 times higher, respectively. Partitioning took
      place mainly in the bottom phase with specific activity being 4.5 and 3.5 times
      higher, respectively. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629802
TI  - Properties of two insect cell lines useful for the baculovirus expression system
      in serum-free culture.
AB  - The properties of Sf9 and Tn5 insect cells were analyzed comparatively under
      serum-free culture conditions. Sf9 cells in SF900II medium apparently utilized
      sucrose as a primary nutrient both before and after virus infection, yielding
      small amounts of lactate and ammonia. Tn5 cells in Excell 401 medium consumed all
      the nutrients examined, including sucrose. The productivity of a recombinant
      glycoprotein, OSF-2, by Tn5 cells, was moderate in both monolayer and spinner
      cultures, but the ability to secrete it was compromised in the former case.
      Relative to the Tn5 cultures, Sf9 produced 30-fold more OSF-2 in either culture
      mode. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629803
TI  - Silk fibroin solution properties related to assembly and structure.
AB  - The impact of physiological factors on silk fibroin solution properties was
      studied. Specifically, the impact of fibroin concentration, protein purity,
      cation type and concentration, and pH on aqueous solution viscosity, shear
      behavior, and surface tension were assessed in the context of silk protein
      assembly. The results demonstrate that in vitro results could be correlated to in
      vivo processing events during silk spinning. Rheological properties with
      reference to the amphiphilic block structure of the protein are described, pH
      dependency of shear response was quantitatively correlated to the predicted pI
      values of the fibroin protein, and cooperativity among environmental factors such
      as pH and salts was identified. Stabilization of silk fibroin solution states by
      calcium was identified as a mode to control shear sensitivity of the fibroin
      solution. The cooperativities identified suggest tight control of fibroin aqueous
      solution rheological properties to gain a window of protection against premature
      crystallization of the fibroin during processing, assuring safe storage,
      transport, and finally successful fiber spinning.

PMID- 18629804
TI  - Functional magnetic resonance imaging monitoring of pathological changes in
      rodent livers during hyperoxia and hypercapnia.
AB  - Liver diseases and regeneration are associated with hemodynamic changes denoting
      pathological alterations. Determining and monitoring physiological and
      pathological liver changes is essential for diagnostic and therapeutic
      objectives. Our aim was to determine the feasibility of functional magnetic
      resonance imaging (fMRI) during hypercapnia and hyperoxia for monitoring liver
      pathology. Liver fMRI images were acquired in rodents following acute bleeding,
      partial hepatectomy, and fibrosis. Results were quantitated and confirmed by
      histology. Changes induced by hyperoxia and hypercapnia following hemorrhage
      significantly correlated with the percentage of blood loss, reflecting lower
      liver perfusion and diminished vessel responsiveness to gas saturation.
      Hepatectomy resulted in an early decline in signal intensity changes due to
      hyperoxia, suggesting a decrease in liver perfusion and blood content. Following
      hepatectomy, signal intensity changes due to hypercapnia increased, signifying a
      change in liver perfusion from a mainly portal to a more arterial source. Two
      weeks after induction of fibrosis, signal intensity changes due to hypercapnia
      became much lower and those due to hyperoxia were much higher than those in
      normal livers, reflecting the increased perfusion due to the inflammatory process
      as confirmed by histologic analysis. With fibrosis progression, signal intensity
      changes induced by hypercapnia and hyperoxia were gradually attenuated,
      indicating structural and functional alterations of the liver vasculature during
      fibrosis. CONCLUSION: In various liver pathologies, fMRI response to hypercapnia
      and hyperoxia is sensitive to changes in liver hemodynamic status involved in
      hepatic damage or recovery; thus, this technique may offer an additional
      noninvasive diagnostic tool for evaluation and follow-up of liver diseases by
      means of examining perfusion-related alterations.

PMID- 18629805
TI  - Force-field modeling through quantum mechanical calculations: molecular dynamics
      simulations of a nematogenic molecule in its condensed phases.
AB  - Interaction energy of the 4-n-pentyloxy-4'-cyanobiphenyl (5OCB) dimer is computed
      at MP2 level, for many geometrical arrangements using the Fragmentation
      Reconstruction Method (FRM). DFT calculations are performed for a number of
      geometries of the monomer. The resulting database is used to parameterize an
      atomistic intra- and inter-molecular force-field suitable for classical bulk
      simulations. Several structural and dynamical properties in 5OCB isotropic and
      liquid crystalline phases are computed from molecular dynamics simulation mainly
      in the NPT ensemble. Lengthy runs (more than 70 ns) and large sample sizes (up to
      806 molecules) were used to determine the nematic to isotropic transition
      temperature up to a precision of few K. Good agreement was found in most of the
      investigated properties, thus validating the accuracy of the proposed model
      potential, only derived by quantum mechanical calculations.

PMID- 18629806
TI  - Application of semiempirical long-range dispersion corrections to periodic
      systems in density functional theory.
AB  - Ewald summation is used to apply semiempirical long-range dispersion corrections
      (Grimme, J Comput Chem 2006, 27, 1787; 2004, 25, 1463) to periodic systems in
      density functional theory. Using the parameters determined before for molecules
      and the Perdew-Burke-Ernzerhof functional, structure parameters and binding
      energies for solid methane, graphite, and vanadium pentoxide are determined in
      close agreement with observed values. For methane, a lattice constant a of 580 pm
      and a sublimation energy of 11 kJ mol(-1) are calculated. For the layered solids
      graphite and vanadia, the interlayer distances are 320 pm and 450 pm,
      respectively, whereas the graphite interlayer energy is -5.5 kJ mol(-1) per
      carbon atom and layer. Only when adding the semiempirical dispersion corrections,
      realistic values are obtained for the energies of adsorption of C(4) alkenes in
      microporous silica (-66 to -73 kJ mol(-1)) and the adsorption and chemisorption
      (alkoxide formation) of isobutene on acidic sites in the micropores of zeolite
      ferrierite (-78 to -94 kJ mol(-1)). As expected, errors due to missing self
      interaction correction as in the energy for the proton transfer from the acidic
      site to the alkene forming a carbenium ion are not affected by the dispersion
      term. The adsorption and reaction energies are compared with the results from
      Moller-Plesset second-order perturbation theory with basis set extrapolation.

PMID- 18629807
TI  - Modeling high pressure reactivity in unsaturated systems: application to
      dimethylacetylene.
AB  - A general model is introduced to study pressure-induced reactivity on unsaturated
      systems in the condensed state. The model is applied here to dimethylacetylene
      (DMA) in the solid phase II (C/2m) because it has been proposed that two DMA
      molecules can react to form tetramethyl-cyclobutadiene (TMCBD). The proposed
      reaction process has been modeled by studying the structural and electronic
      changes undergone by two DMA molecules as they approach each other preserving the
      crystal symmetry of phase II. Both monodeterminantal (MP2 and DFT) and
      multideterminantal (CASSCF and MRMP2) methodologies were used to check the
      reliability of our model in predicting the reactivity of the system under
      compression. In all cases, structural results are in agreement with low
      temperature diffraction experiments for the solid phase II. Our model indicates
      that DMA is expected to form the TMCBD dimer at intermolecular distances close to
      2 A. This value is in excellent agreement with previous calculations on the
      existence of long carbon-carbon bonds.

PMID- 18629808
TI  - Site specificity of the (alpha)C--H bond dissociation energy for a naturally
      occurring beta-hairpin peptide-An ab initio study.
AB  - A naturally occurring beta-hairpin peptide (PDB ID 1UAO) was used as a model to
      study the backbone oxidation of a protein with ab initio calculation at the
      B3LYB/6-31G(d) without any constraints. The (alpha)C--H bond dissociation energy
      of three different glycyl radicals located at different sites on the beta-hairpin
      peptide was calculated to evaluate the site specificity of backbone oxidation.
      The molecular and electronic structures of these glycyl radicals were analyzed to
      rationalize this site specificity. The overall molecular structure of the alpha-H
      abstracted beta-hairpin peptide remained almost unchanged with the exception of
      the local conformation of the attacked residue. However, the (alpha)C--H bond
      strength varied dramatically among these different sites.

PMID- 18629809
TI  - Moller-Plesset perturbation energies and distances for HeC(20) extrapolated to
      the complete basis set limit.
AB  - The potential energy surface for the C(20)-He interaction is extrapolated for
      three representative cuts to the complete basis set limit using second-order
      Moller-Plesset perturbation calculations with correlation consistent basis sets
      up to the doubly augmented variety. The results both with and without
      counterpoise correction show consistency with each other, supporting that
      extrapolation without such a correction provides a reliable scheme to elude the
      basis-set-superposition error. Converged attributes are obtained for the C(20)-He
      interaction, which are used to predict the fullerene dimer ones. Time
      requirements show that the method can be drastically more economical than the
      counterpoise procedure and even competitive with Kohn-Sham density functional
      theory for the title system.

PMID- 18629810
TI  - Enveloping triangulation method for detecting internal cavities in proteins and
      algorithm for computing their surface areas and volumes.
AB  - Detection and quantitative characterization of the internal cavities in proteins
      remain an important topic in studying protein structure and function. Here we
      propose a new analytical method for detecting the existence of cavities in
      proteins. The method is based on constructing the special enveloping
      triangulation enclosing the cavities. Based on this method, we develop an
      algorithm and a fortran package, CAVE, for computing volumes and surface areas of
      cavities in proteins. We first test our method and algorithm in some artificial
      systems of spheres and find that the calculated results are consistent with exact
      results. Then we apply the package to compute volumes and surface areas of
      cavities for some protein structures in the Protein Data Bank. We compare our
      calculated results with those obtained by some other methods and find that our
      approach is reliable.

PMID- 18629811
TI  - Zinc oxide: A case study in contemporary computational solid state chemistry.
AB  - Computational techniques have been applied to study a broad range of chemical and
      physical properties of zinc oxide. Both interatomic-potential and density
      functional theory methods are used to investigate structural, thermodynamic,
      surface, and defect properties. We survey the structures and energies of nano
      particulate zinc oxide.

PMID- 18629813
TI  - A self-tuning vision system for monitoring biotechnological processes: I.
      Application to production of pullulan by Aureobasidium pullulans.
AB  - A prototype of a self-tuning vision system (STVS) has been developed to monitor
      cell population in fermentations. The STVS combines classical image processing
      techniques, neural networks and fuzzy logic technologies. By combining these
      technologies the STVS is able to analyze sampled images of the culture. The
      proposed system can be "tailored" with minimum effort by an expert who can
      "teach" the system to recognize cells by showing examples of different
      morphologies. After adaptation, the STVS is able to capture images, isolate the
      different cells, classify them according to the expert's criteria, and provide
      the profile of the cell's population. The system was applied to the
      classification and analysis of Aureobasidium pullulans. The importance of
      understanding the changes of population distribution during the fermentation and
      its effect in the production of pullulan are emphasized. The STVS can be used for
      monitoring and control of the cell population in small research fermentors or in
      large-scale production.

PMID- 18629814
TI  - A novel centrifugal impeller bioreactor. I. Fluid circulation, mixing, and liquid
      velocity profiles.
AB  - A novel centrifugal impeller bioreactor for shear-sensitive biological systems
      was designed by installing a centrifugal-pumplike impeller in a stirred vessel.
      The fluid circulation, mixing, and liquid velocity profiles in the new bioreactor
      (5-L) were assessed as functions of the principal impeller designing and
      bioreactor operating parameters. The performances of the centrifugal impeller
      bioreactor were compared with those of a widely used cell-lift bioreactor. The
      newly developed bioreactor showed higher liquid lift capacity and shorter mixing
      time than the cell lift with comparable dimensions. Furthermore, the experiments
      of the liquid velocity profiles around an impeller region indicated that the
      centrifugal impeller bioreactor produced lower shear stress than the cell lift.
      This conclusion was also supported by evaluating the changes in size
      distributions of granulated agar particles that were sheared with those two types
      of impeller.

PMID- 18629815
TI  - A novel centrifugal impeller bioreactor. II. Oxygen transfer and power
      consumption.
AB  - The effects of the impeller configuration, aeration rate, and agitation speed on
      oxygen transfer coefficient K(L)a were studied in a newly designed centrifugal
      impeller bioreactor (5-L). The oxygen transfer rates in the novel bioreactor were
      also compared with those in a cell-lift bioreactor with comparable dimensions.
      The cell-lift impeller produced much higher surface oxygen transfer rates than
      the centrifugal one at an agitation speed over 200 rpm. This result was in good
      agreement with our observation that the cell-lift impeller produced much higher
      unfavorable turbulence. In addition, the experiments using granulated agar
      particles as pseudo plant cells indicated that the K(L)a value decreased steadily
      with an increase in agar particle concentration, and the centrifugal impeller
      still demonstrated a larger K(L)a than the cell lift up to a high pseudo cell
      concentration of 19.5 g dry weight (DW)/L (under 150 rpm and 0.20 vvm) or 22.3 g
      DW/L (under 200 rpm and 0.20 vvm). Furthermore, the correlation between power
      number and impeller Reynolds number for both the centrifugal and the cell-lift
      impellers was successfully obtained, which could be used for predicting the power
      input required by each impeller. From the results obtained, the centrifugal
      impeller bioreactor is expected to have great potential in its application to
      shear-sensitive biological systems.

PMID- 18629816
TI  - Degradation of chloro- and methyl-substituted benzoic acids by a genetically
      modified microorganism.
AB  - Degradation of 3-chlorobenzoic acid (3CB), 4-chlorobenzoic acid (4CB), and 4
      methylbenzoic acid (4MB) as single substrates (carbon sources) and as a substrate
      mixture were studied in batch and continuous culture using the genetically
      modified microorganism Pseudomonas sp. B13 FR1 SN45P. The strain was able to
      mineralize the single compounds as well as the substrate mixture completely.
      Conversion of the three compounds in the substrate mixture proceeded
      simultaneously. Maximum specific substrate conversion rates were calculated to be
      0.9 g g(-1) h(-1) for 3 CB and 4CB and 1.1 g g(-1) h(-1) for 4MB. Mass balances
      indicated the transient accumulation of pathway intermediates during batch
      cultivations. Hence, the rate limiting step in the degradative pathway is not the
      initial microbial attack of the original substrate or its transport through the
      cell membrane. Degradation rates on 3CB were comparable to those of the parent
      strain Pseudomonas sp. B13. The stability of the degradation pathways of strain
      Pseudomonas sp. B13 FR1 SN45P could be demonstrated in a continuous cultivation
      over 3.5 months (734 generation times) on 3CB, 4MB, and 4CB, which were used as
      single carbon sources one after the other.

PMID- 18629817
TI  - NMR imaging of heavy metal absorption in alginate, immobilized cells, and kombu
      algal biosorbents.
AB  - In this contribution, an NMR imaging study of heavy metal absorption in alginate,
      immobilized-cell biosorbents, and kombu (Laminaria japonica) algal biomass is
      presented. This method provides the good possibility of directly monitoring the
      time evolution of the spatial distribution of the ions in the materials. From
      these results, we demonstrate that rare earth ions are absorbed with a steep
      reaction front that can be described very well with a modified shrinking core
      model, while copper ions are absorbed with a more diffuse front.

PMID- 18629818
TI  - Enzymatic resolution of 1-phenyl-1,2-ethanediol by enantioselective oxidation:
      overcoming product inhibition by continuous extraction.
AB  - Oxidations of alcohols by alcohol dehydrogenases often suffer from low
      conversions and slow reaction rates due to severe product inhibition. This can be
      overcome by continuous product extraction, because only the concentrations, but
      not the kinetic parameters, can be changed. As a consequence, it is favorable to
      apply a differential circulation reactor with continuous product extraction,
      where only a small amount of product is formed per cycle. The product is then
      directly extracted using a microporous hydrophobic hollow fiber membrane. This
      results in an increase of the relative activity of the dehydrogenase at a given
      conversion. The reaction investigated is the kinetic resolution of racemic 1
      phenyl-1,2-ethanediol by glycerol dehydrogenase (GDH). The resulting oxidation
      product, 2-hydroxyacetophenone, causes a strong product inhibition. Additionally,
      it reacts in a chemical reaction with the cofactor lowering its active
      concentration. Because the GDH needs beta-nicotinamide adenine dinucleotide
      (NAD(+)) as a cofactor, lactate dehydrogenase is used to regenerate NAD(+) from
      NADH by reducing pyruvate to (L)-lactate. A conversion of 50% with respect to the
      racemate and an enantiomeric excess >99% of the (S)-enantiomer was reached.

PMID- 18629819
TI  - Effects of nitrate and acetate availability on chloroform production during
      carbon tetrachloride destruction.
AB  - Fed batch experiments were performed to test the effects of electron donor and
      electron acceptor availability on the production of chloroform (CF) during carbon
      tetrachloride (CT) destruction by a denitrifying bacterial consortium. In one
      series of tests, acetate (electron donor) was present in excess while nitrate and
      nitrite (electron acceptor) were limiting. In the other series of tests, acetate
      was the limiting nutrient, and nitrate and nitrite were in excess. Under nitrate
      limiting conditions, 50% (+/-17%) of the CT transformed by the microorganisms was
      converted to CF. However, under acetate limiting conditions, only 4% (+/-4%) of
      the CT that was degraded appeared as CF. Previous research had suggested that
      denitrifying bacteria can degrade CT via two competing pathways. One of these
      pathways produces CF as the predominant end product. The second pathway produces
      CO(2) as the primary end product. The results shown here suggest that the first
      pathway is dominant when nitrate and nitrite are depleted while the second
      pathway, which produces little CF, dominates when nitrate or nitrite are
      available.

PMID- 18629820
TI  - A structured model for hyphal differentiation and penicillin production using
      Penicillium chrysogenum.
AB  - A structured kinetic model describing growth, differentiation, and penicillin
      production in submerged Penicillium chrysogenum fermentations is reported. The
      filamentous hyphae are divided into four distinct regions on the basis of the
      activities and structure of hyphal compartments, viz., actively growing (mainly
      apical) regions, nongrowing or penicillin producing regions, vacuoles, and
      degenerated or metabolically inactive regions. A mechanistic approach is taken to
      give quantitative descriptions of differentiation and degeneration as a
      consequence of vacuolation. The growth and degeneration of vacuoles are expressed
      in the form of a population balance. The model assumes that newly generated
      vacuoles appear by differentiation of healthy regions, grow in size with
      limitation of available substrate, and eventually give rise to empty hyphal
      compartments. In the model the penicillin production is related to the amounts of
      the nongrowing regions of the hyphae. The model is used for successful
      predictions of the amounts of the four hyphal regions and the penicillin G
      production rate throughout the fed-batch fermentations of an industrial P.
      chrysogenum strain under different glucose feeding regimes. Quantitative
      information on proportions of the hyphal regions was obtained from image analysis
      measurements and the parameters of the kinetic model were identified. When the
      glucose feed rate to the production culture is switched between a high and a low
      value, the model can successfully predict the dynamic changes of differentiation
      and the resulting penicillin production caused by the variations in the nutrient
      conditions. The use of image analysis to characterize differentiation as a basis
      for structured modeling of the penicillin fermentation appears to be very
      powerful, and the method has great potential for use in process simulation and
      control of antibiotic fermentations.

PMID- 18629821
TI  - Investigation of behavior of an enzyme in a biphasic system: soybean lipoxygenase
      1.
AB  - Soybean lipoxygenase-1 (EC 1.13.11.12) reaction with linoleic acid as substrate
      was used to study the biocatalysis in a biphasic system when the reactants have
      surface-active properties. The poorly water-soluble substrate was initially
      dissolved in an apolar solvent (octane). The hydroperoxide produced was water
      soluble and remained in the aqueous phase (borate buffer). The bioreactor was a
      modified Lewis cell with a well-defined interfacial area between the two phases.
      Two phenomena were studied separately: the reactant transfer between the two
      phases and the biocatalyzed reaction in an aqueous medium. This allowed
      determination of the transfer and the reaction constants. Substrate transfer was
      found to be affected by the progress of the reaction, because linoleic acid and
      the hydroperoxy acid have an influence on the interfacial tension. Inactivation
      of the biocatalyst at the interface was observed in the bioreactor. These results
      indicate that it is impossible to analyze the system behavior with the method
      proposed in the literature, which is based on the sequential study of the
      substrate transfer to the aqueous phase and its biocatalysis by lipoxygenase. The
      interaction between transfer phenomena and reaction kinetics was studied in the
      biphasic system. The kinetics were different from those obtained in the aqueous
      medium. Catalysis and transfer influence each other reciprocally. In this
      compartmentalized system, cooperativity phenomena were obtained using a
      nonallosteric enzyme. The evolution of the system was modeled (Runge-Kutta
      algorithm). The curves obtained were very close to those determined
      experimentally.

PMID- 18629822
TI  - Immobilization of DNA onto a polymer support and its potentiality as
      immunoadsorbent.
AB  - Immobilization of DNA to the surface of poly(ethylene terephthalate) (PET)
      microfibers with a high specific surface area of 0.83 m(2)/g was carried out to
      give the fiber surface an affinity for anti-DNA antibody. Following ozone
      oxidation, the microfibers were subjected to graft polymerization of monomers
      including acrylic acid, methacryloyloxyethyl phosphate, N,N-dimethylaminoethyl
      methacrylate, N-vinylformamide, and glycidyl methacrylate. Calf thymus DNA was
      immobilized to the grafted fiber surface through either covalent binding or
      polyion complexation with the grafted polymer chains. The highest surface density
      of DNA immobilized (0.6 microg/cm(2)) was obtained when DNA was immobilized
      through formation of phosphodiester linkage between the hydroxyl group of DNA and
      the phosphate group in grafted poly(methacryloyloxyethyl phosphate) using 1,1
      carbonyldiimidazole, or through polyion complexation between the anionic DNA and
      the cationic grafted poly(N,N-dimethylaminoethyl methacrylate) chains. Batch
      adsorption of anti-DNA antibody to the grafted PET fibers with and without DNA
      immobilized on their surface was conducted with serum obtained from systemic
      lupus erythematosus model mice. The DNA-immobilized PET fibers exhibited a higher
      adsorption capacity and specificity than the others. In addition, the DNA
      immobilized fibers effectively adsorbed human anti-DNA antibody.

PMID- 18629823
TI  - Generation of colorimetric, dual signals from two different enzymes by using
      catalytic pH shift.
AB  - Because enzymes usually require distinct pH conditions for maximum activity, an
      approach of spontaneous pH shift of solution was devised to derive multiple
      reactions in a sequence. The two enzymes selected, horseradish peroxidase (HRP)
      and beta-galactosidase (GAL), had dissimilar optimal pH levels, i.e., 5.1 and
      7.0, respectively. In a solution, HRP initially reacted at a lower pH range and
      the GAL reaction was consecutively carried out at a higher range in the presence
      of a third enzyme, urease, which caused an increase in pH. Under optimal
      conditions, the multiple system provided comparable performances with those of
      single reactions.

PMID- 18629824
TI  - A practical kinetic model that considers endproduct inhibition in anaerobic
      digestion processes by including the equilibrium constant.
AB  - The classical Michaelis-Menten model is widely used as the basis for modeling of
      a number of biological systems. As the model does not consider the inhibitory
      effect of endproducts that accumulate in virtually all bioprocesses, it is often
      modified to prevent the overestimation of reaction rates when products have
      accumulated. Traditional approaches of model modification use the inclusion of
      irreversible, competitive, and noncompetitive inhibition factors. This article
      demonstrates that these inhibition factors are insufficient to predict product
      inhibition of reactions that are close the dynamic equilibrium. All models
      investigated were found to violate thermodynamic laws as they predicted positive
      reaction rates for reactions that were endergonic due to high endproduct
      concentrations. For modeling of biological processes that operate close to the
      dynamic equilibrium (e.g., anaerobic processes), it is critical to prevent the
      prediction of positive reaction rates when the reaction has already reached the
      dynamic equilibrium. This can be achieved by using a reversible kinetic model.
      However, the major drawback of the reversible kinetic model is the large number
      of empirical parameters it requires. These parameters are difficult to determine
      and prone to experimental error. For this reason, the reversible model is not
      practical in the modeling of biological processes.This article uses the
      fundamentals of steady-state kinetics and thermodynamics to establish an equation
      for the reversible kinetic model that is of practical use in bio-process
      modeling. The behavior of this equilibrium-based model is compared with Michaelis
      Menten-based models that use traditional inhibition factors. The equilibrium
      based model did not require any empirical inhibition factor to correctly predict
      when reaction rates must be zero due to the free energy change being zero. For
      highly exergonic reactions, the equilibrium-based model did not deviate
      significantly from the Michaelis-Menten model, whereas, for reactions close to
      equilibrium, the reaction rate was mainly controlled by the quotient of mass
      action ratio (concentration of all products over concentration of all substrates)
      over the equilibrium constant K. This quotient is a measure of the displacement
      of the reaction from its equilibrium. As the new equation takes into account all
      of the substrates and products, it was able to predict the inhibitor effect of
      multiple endproducts. The model described is designed to be a useful basis for a
      number of different model applications where reaction conditions are close to
      equilibrium.

PMID- 18629825
TI  - Influence of the degree and mode of light limitation on growth characteristics of
      the Rhodobacter capsulatus continuous cultures.
AB  - The influence of the degree and mode of light limitation on growth
      characteristics of turbidostat cultures of Rhodobacter capsulatus was
      investigated using mass and energy balance regularities. Light limitation was
      achieved by increasing the steady-state biomass concentration at constant
      incident light intensity ( approximately 100 W/m(2)) or by decreasing the
      incident light intensity at constant steady-state biomass concentration (
      approximately 500 mg of dry biomass/L). It was shown that under conditions of
      light limitation of Rh. capsulatus, the content of P and N in the biomass as well
      as the biomass degree of reduction were determined by the growth rate of the
      cultures. The energetic yield of biomass of Rh. capsulatus and total
      bacteriochlorophyll a content increased when light limitation increased. These
      parameters were higher in the cultures, in which light limitation was achieved by
      lowering the incident light intensity at low biomass concentration. This seems to
      be due to different distribution of light within the photobioreactor when
      dissimilar modes of light limitation were used.

PMID- 18629826
TI  - A novel 154-bp deletion in the human mitochondrial DNA control region in healthy
      individuals.
AB  - The biological role of the mitochondrial DNA (mtDNA) control region in mtDNA
      replication remains unclear. In a worldwide survey of mtDNA variation in the
      general population, we have identified a novel large control region deletion
      spanning positions 16154 to 16307 (m.16154_16307del154). The population
      prevalence of this deletion is low, since it was only observed in 1 out of over
      120,000 mtDNA genomes studied. The deletion is present in a nonheteroplasmic
      state, and was transmitted by a mother to her two sons with no apparent past or
      present disease conditions. The identification of this large deletion in healthy
      individuals challenges the current view of the control region as playing a
      crucial role in the regulation of mtDNA replication, and supports the existence
      of a more complex system of multiple or epigenetically-determined replication
      origins.

PMID- 18629828
TI  - Improvement of recombinant protein production with the human adenovirus/293S
      expression system using fed-batch strategies.
AB  - The human adenovirus/293S cell expression system is used for the production of
      either recombinant protein or adenovirus vectors for use in gene therapy. In this
      work, the production of protein tyrosine phosphatase (PTP1C) was used as a model
      for the scale-up of both applications. Maximum specific production of 30 to 45
      mug of active protein/10(6) cells was maintained upon infection with adenovirus
      vectors at cell densities between 2 x 10(6) to 3 x 10(6) cells/mL in a 3.5-L
      bioreactor. This was achieved by resuspending the culture in fresh medium at
      infection time. The pH was kept at 7.0 throughout the experiment and, at 24 h
      postinfection, glucose and essential amino acids were added. Attempts to replace
      the complete change of medium at the time of infection with nutrient
      supplementation of the used medium led to lower production levels, suggesting
      that protein expression was limited not by the absence of a key nutrient but by
      inhibitory factors. Two potentially inhibitory factors were investigated: lactic
      acid accumulation and increased osmolarity. Medium acidification such as that
      which would be brought about by lactic acid accumulation was shown to depress
      PTP1C production. The lactate molecule itself decreased the cell viability when
      added in concentrations of 20 mM or more. But the specific productivity was
      affected at higher lactate concentrations of 40 mM or more. Additions of glucose,
      amino acids, and NaHCO(3) used to control pH, led to increases in osmolarity.
      Osmolarities above 400 mOsm lowered cell density. However, specific production
      was not significantly affected below 500 mOsm. But, at 500 mOsm, PTP1C production
      peak was shifted from 48 to 72 hpi. Because of the cell loss, this per cell yield
      increase did not translate into higher volumetric production. When glucose
      concentrations was kept at 5 mM by fed-batch addition, lactate production and
      increases in osmolarity were reduced. In shake flasks, this method permitted
      maximum production with cells resuspended either in fresh or spent medium at
      infection. This fed-batch process was implemented successfully at the 3.5-L
      scale. Fed-batch with glucose may provide a means to increase infected-cell
      density beyond 3 x 10(6) cells/mL.

PMID- 18629829
TI  - Development and application of a membrane cyclone reactor for in vivo NMR
      spectroscopy with high microbial cell densities.
AB  - A new bioreactor system has been developed for in vivo NMR spectroscopy of
      microorganisms under defined physiological conditions. This cyclone reactor with
      an integrated NMR flow cell is continuously operated in the magnet of a 400-MHz
      wide-bore NMR spectrometer system. The residence times of medium and cells are
      decoupled by a circulation-integrated cross-flow microfiltration module to
      achieve higher cell densities as compared to continuous fermentations without
      cell retention (increase in cell density up to a factor of 10 in steady state).
      Volumetric mass transfer coefficients k(L)a of more than 1.0 s(-1) are possible
      in the membrane cyclone reactor, ensuring adequate oxygen supply [oxygen transfer
      rate >15,000 mg O(2) .(L h)(-1)] of high cell densities. With the aid of the
      membrane cyclone reactor we were able to show, using continuous in vivo (31)P NMR
      spectroscopy of anaerobic glucose fermentation by Zymomonas mobilis, that the NMR
      signal intensity was directly proportional to the cell concentration in the
      reactor. The concentration profiles of intracellular inorganic phosphate, NAD(H),
      NDP, NTP, UDP-sugar, a cyclic pyrophosphate, two sugar phosphate pools, and
      extracellular inorganic phosphate were recorded after a shift from one steady
      state to another. The intracellular cyclic pyrophosphate had not been detected
      before in in vitro measurements of Zymomonas mobilis extracts due to the high
      instability of this compound. Using continuous in vivo (13)C NMR spectroscopy of
      aerobic glucose utilization by Corynebacterium glutamicum at a density of 25
      g(cell dry weight) . L(-1), the membrane cyclone reactor served to measure the
      different dynamics of labeling in the carbon atoms of L-lactate, L-glutamate,
      succinate, and L-lysine with a time resolution of 10 min after impressing a [1
      (13)C]-glucose pulse.

PMID- 18629830
TI  - NMR on-line monitoring of esterification catalyzed by cutinase.
AB  - A nuclear magnetic resonance (NMR) method has been developed to monitor on-line
      lipase-catalyzed esterification reactions without the need to sample the reaction
      medium. The technique, through (1)H NMR, measures the concentrations of alcohol,
      ester, hydroxylic hydrogens in the organic phase, and hydroxylic hydrogens in the
      aqueous phase, if any. Also, the chemical shift evolution of the two types of
      hydroxylic hydrogens has been followed, providing information on water content of
      the organic phase and on the appearance of a distinct aqueous phase. As far as
      (13)C NMR is concerned, it has been possible to measure, first the acid and the
      ester concentrations in the carbonyl region, and second, the alcohol and the
      ester concentrations in the methylene region. All (1)H and (13)C results are in
      agreement with one another. Furthermore, NMR allows for the choice of detection
      zone. Preliminary studies on the solid phase proved the presence of much more
      water in the solid phase than in the organic phase, and also gave evidence of the
      existence of two types of esters, one in the organic phase, mainly associated
      with the acid, and the other one not associated with the acid, most probably
      entrapped within the solid enzyme.

PMID- 18629831
TI  - Continuous cultures limited by a gaseous substrate: Development of a simple,
      unstructured mathematical model and experimental verification with
      Methanobacterium thermoautotrophicum.
AB  - This article presents a simple, unstructured mathematical model describing
      microbial growth in continuous culture limited by a gaseous substrate. The model
      predicts constant gas conversion rates and a decreasing biomass concentration
      with increasing dilution rate. It has been found that the parameters influencing
      growth are primarily the gas transfer rate and the dilution rate. Furthermore, it
      is shown that, for correct simulation of growth, the influence of gaseous
      substrate consumption on the effective gas flow through the system has to be
      taken into account.Continuous cultures of Methanobacterium thermoautotrophicum
      were performed at three different gassing rates. In addition to the measurement
      of the rates of biomass production, product formation, and substrate consumption,
      microbial heat dissipation was assessed using a reaction calorimeter. For the on
      line measurement of the concentration of the growth-limiting substrate, H(2), a
      specially developed probe has been used. Experimental data from continuous
      cultures were in good agreement with the model simulations. An increase in
      gassing rate enhanced gaseous substrate consumption and methane production rates.
      However, the biomass yield as well as the specific conversion rates remained
      constant, irrespective of the gassing rate. It was found that growth performance
      in continuous culture limited by a gaseous substrate is substantially different
      from "classic" continuous culture in which the limiting substrate is provided by
      the liquid feed. In this report, the differences between both continuous culture
      systems are discussed.

PMID- 18629832
TI  - Attachment/detachment and trichloroethylene degradation-longevity of a resting
      cell Methylosinus trichosporium OB3b filter.
AB  - We are investigating a methanotrophic filter strategy for the in situ
      bioremediation of low levels of chlorinated aliphatic, volatile organic chemicals
      (VOCs). It is based on the use of pregrown, resting cells, instead of growth
      nutrient stimulations. The economic feasibility of such a filter is dependent on
      its operational longevity at ground-water temperatures. The latter, in turn, is
      dependent on several key parameters, such as the bacterial attachment densities
      reached during the injection of the microbial suspension and the subsequent
      detachment-removal of cells from the filter over time. Scaled
      attachment/detachment experiments were carried out using a representative
      quartzitic sand in glass 1-cm x 10-cm columns to simulate a filter. A rosette
      dominated form of Methylosinus trichosporium OB3b was isolated and used in these
      and the subsequent catalytic longevity experiments. Its initial attachment,
      employing Higgins' medium phosphate buffer, pH 7.0 (HPB), was 7.0 to 8.0 x 10(8)
      bacteria/g of dry sand. This was elevated to approximately 1.5 x 10(9) cells/g by
      including 1.0 mM MgCl(2), 100 muM FeSO(4), and 0.025% agar in the cell-suspension
      loading buffer. These loading additives also increased the time required to reach
      50% cell detachment with HPB alone from 5 days to approximately 45 days. The
      functional longevity of a column biofilter, formed with resting-state rosette
      enriched cells in the presence of the aforementioned additives, was determined at
      21 degrees C by challenging it with weekly 12 h, approximately 250 ppb pulses of
      trichloroethylene (TCE). The column results indicate that for our attached-cell
      filter to biodegrade TCE levels of several hundred ppb sufficiently, to <5 ppb,
      it will likely need replenishment at approximately 8 week intervals, due to the
      instability of the endogenous whole-cell soluble methane monooxygenase specific
      activity beyond that time period. This study represents the first time that
      anyone has shown that a rosette-enriched substrain can be isolated from a well
      known methanotrophic strain and then stably cultured and utilized advantageously
      for a specific application-namely its improved attachment-slowed detachment
      characteristics in a microbial filter.

PMID- 18629833
TI  - Sizing and counting of saccharomyces cerevisiae floc populations by image
      analysis, using an automatically calculated threshold.
AB  - A standardized image analysis method has been developed permitting determination
      of the number of yeast flocs and their size distribution. The method includes
      image grabbing, image enhancement, automatic determination of the appropriate
      threshold, curve fitting of the areahistogram, determination of the mean single
      floc area and its standard deviation, and floc counting. The extension of the
      method to other applications is immediate and straightforward. Two Saccharomyces
      cerevisiae floc Populations (with ages of 48 and 72 h) were analyzed. The results
      showed a variation around the mean of 9%-12% for the single floc mean area, 6%-7%
      for the number of single flocs, and 5%-6% for the total number of flocs.
      Aggregates of two flocs (doublets) and three flocs (triplets) were enumerated.
      The correctness of the method was checked by analyzing the parameters of interest
      as a function of the threshold. The constant correlation between the parameters
      and the threshold showed the validity and consistency of the method. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18629834
TI  - Morphological characterization of the dimorphic yeast Kluyveromyces marxianus
      var. marxianus NRRLy2415 by semi-automated image analysis.
AB  - A semiautomatic image analysis method has been developed to characterize the
      morphology of the dimorphic yeast Kluyveromyces marxianus var. marxianus
      (formerly fragilis) NRRLy2415 undergoing alcoholic fermentation of cheese whey
      permeate. The method is capable of separating cells into six defined categories,
      varying from simple ovoid yeast cells to branched mycelial cells. A sample size
      of 300 cells was found to be sufficient to obtain a statistically significant
      categorization. The processing time for a sample was found to be approximately 90
      min. In addition to qualitative characterization, the method permits the
      measurement of geometric properties such as the width, length, and volume of
      individual cells or clusters of cells. When the cells analyzed by the automatic
      method were categorized on a manual basis, the error level in the automatic
      routine was found to be less than 3%.

PMID- 18629835
TI  - Endoplasmic reticulum protein expression in recombinant NS0 myelomas grown in
      batch culture.
AB  - During batch growth of two recombinant NS0 myelomas, an increase in the
      expression of the endoplasmic reticulum (ER) proteins (GRP78/BiP, GRP94, and
      ERp72) was observed. A marked increase in these proteins was associated with the
      decline phase of growth, an increase in the production rate of chimeric antibody,
      and a marked slowing or halt in the uptake of glucose and glutamate. Refeeding
      with glucose, glutamate, or a mixture of amino acids just prior to the onset of
      decline phase failed to repress induction. Although refeeding with glutamate led
      to an increase in specific productivity, there was no significant difference in
      the pattern of ER protein induction. These results indicate that an increase in
      ER protein expression is not solely related to productivity but also to certain
      changes that occur during the course of batch growth.

PMID- 18629836
TI  - Effect of oxygen supply on metabolism of immobilized and suspended Escherichia
      coli.
AB  - The effect of reduced oxygen supply on the production of a recombinant protein
      (plasmid-encoded beta-galactosidase) was investigated in Escherichia coli. A
      novel modified bubble tank reactor was used to provide a direct comparison
      between immobilized and suspended cells in identical environments except for the
      immobilization matrix. Decreased oxygen supply led to increased beta
      galactosidase synthesis by both immobilized and suspended cells. Immobilized
      cells produced similar amounts of beta-galactosidase as the suspended cells.
      Lactose consumption and acetate production, on a per cell basis, were
      significantly higher in immobilized cells, suggesting that immobilized cells
      utilized fermentative metabolism. However, a transport analysis of the
      immobilized cell system showed that immobilized cells were not subject to either
      external or internal mass transfer gradients.

PMID- 18629837
TI  - Site-specific integration of heterologous genes in yeast via Ty3
      retrotransposition.
AB  - The Ty3 retrotransposon of Saccharomyces cerevisiae was employed for the site
      specific integration of heterologous genes into the yeast genome. A GAL-regulated
      promoter allowed induction of the retrotransposition process, and a bacterial
      neo(r) gene inserted in the Ty3 element was used as a selectable model
      heterologous gene. The frequency of transposition of this neo(r)-marked element
      was found to be comparable to that of an unmarked element. Three amplification
      systems were constructed; the systems varied with respect to the location and
      number of the GAL-regulated helper and neo(r)-marked Ty3 elements. For all three
      systems, neo(r) integrations were readily selected with a maximum of two
      insertions obtained per round of amplification. A sequential amplification
      strategy was effective for further increasing the number of integrated cloned
      genes, and families of strains varying by only one neo(r) insertion were easily
      obtained. Resistance to the antibiotic G418 correlated well with the number of
      integrated neo(r) genes, and Northern blots verified the relationship between
      cloned gene number (up to four) and neo(r) expression. Structural stability of
      the integrated genes was also demonstrated. By controlling the number of rounds
      of amplification and the level of G418 selection, precise numbers of integrated
      heterologous genes could be obtained. Because the amplification process can be
      repeated using different cloned genes inserted in the Ty3 element, these results
      demonstrate the potential of retrotransposition for the regulated integration of
      a series of different genes at nondeleterious chromosomal locations.

PMID- 18629838
TI  - An experimental model of biofilm detachment in liquid fluidized bed biological
      reactors.
AB  - Dimensional analysis was applied for the description of biofilm detachment in
      liquid fluidized bed biological reactors. This technique allowed the
      identification of the significant parameters influencing detachment mechanisms
      and suggested suitable experiments for the characterization of involved
      phenomena. The influence of the significant variables was established on a lab
      scale reactor and an empirical model was proposed to correlate experimental
      results. The detachment rate was strongly dependent on liquid velocity, while the
      influence of other parameters, such as solid hold-up and liquid shear stress, was
      found to be less important.

PMID- 18629839
TI  - Electrophysical monitoring of culture process of recombinant Escherichia coli
      strains.
AB  - A novel method for monitoring the cell culture process has been developed. The
      method is based on the measurements of electro-optical characteristics of cell
      suspension, calculation of cell structure parameters, and the relationship
      between accumulation of proteins and change of these parameters' employment.
      Application of the method for the monitoring of a culture process of a
      recombinant strain is considered. The process of growth of recombinant strains
      cannot be sufficiently predicted and the direct measurement of cell culture
      parameters is unlikely to be the most efficient way of solving the
      problem.Escherichia coli plasmid-free and recombinant strains synthesizing the
      fusion protein consisting of tumor necrosis factor-alpha (TNF) and thymosin
      alpha(1) (T) were studied. It was found that cytoplasmic electroconductivity of
      the strains investigated increased during the culture process. The accumulation
      of insoluble recombinant pThy-315-encoded hybrid protein TNF(SINGLEBOND)T in
      cells resulted in a decrease of the membrane dielectric permeability. To
      determine variations of membrane dielectric permeability the amount of insoluble
      recombinant protein TNF(SINGLEBOND)T in the bacterial cells should be calculated.

PMID- 18629840
TI  - High cell density and high monoclonal antibody production through medium design
      and rational control in a bioreactor.
AB  - A simple feeding strategy was developed and successfully employed for nutritional
      control in a 2-L fed-batch culture of hybridoma cells. A previously developed
      stoichiometric model for animal cell growth was used to design a supplemental
      medium for feeding. Undialyzed fetal bovine serum and trace metals (Fe(2+),
      SeO(3) (2-), Li(+), Zn(2+), and Cu(2+)) were fed to the cells periodically in
      addition to the automatic feeding of other nutrients in the supplemental medium.
      In this study, the maximum viable cell density was increased from 6.3 x 10(6) to
      1.7 x 10(7) cells/mL, and the culture span was extended from 340 to 550 hours.
      The final monoclonal antibody titer achieved was 2400 mg/L. The specific
      production rates for ammonia and lactate were further reduced from 0.0045 and
      0.0048 in our previous fed-batch experiments to 0.0028 and 0.0036 mmol/10(9) cell
      h, respectively. Only 3.4% of the total glucose consumption was converted into
      lactate, compared to 67% in a conventional batch culture.

PMID- 18629841
TI  - Advanced bladder cancer: status of first-line chemotherapy and the search for
      active agents in the second-line setting.
AB  - Urothelial carcinoma (UC) remains a significant health problem affecting an
      estimated 68,810 people in 2008 alone in the US. The majority of patients with
      metastatic disease develop disease recurrence, and long-term survival rates are
      poor. There is no standard of care for the treatment of patients with UC after
      the failure of cisplatin-based regimens in the first-line setting. Efforts to
      improve second-line treatment have led to the evaluation of single agents such as
      vinflunine and pemetrexed, and multidrug combinations with cytotoxic and targeted
      agents, including trastuzumab and bevacizumab. The authors reviewed the activity
      of several single agents and combination regimens in patients with UC. Emerging
      strategies for the measurement of response in clinical trials were also outlined.

PMID- 18629842
TI  - The effect of interleukin 11 on thrombocytopenia associated with tyrosine kinase
      inhibitor therapy in patients with chronic myeloid leukemia.
AB  - BACKGROUND: During therapy with tyrosine kinase inhibitors (TKIs), approximately
      20% to 50% of patients with chronic myeloid leukemia (CML) develop grade >or=3
      thrombocytopenia leading to treatment interruptions and dose reductions.
      Interleukin 11 (IL-11) reduces the incidence and the severity of thrombocytopenia
      in solid tumors. METHODS: The authors investigated the efficacy and safety of low
      dose IL-11 for improving thrombocytopenia associated with TKI therapy in 14
      patients with CML. The starting dose of IL-11 was 10 microg/kg 3 times weekly,
      and the dose was escalated by 1 dose level every 2 weeks if the patients had no
      sustained platelet increase. RESULTS: The median patient age was 52 years. The
      median platelet count at the time IL-11 was started was 37 x 10(9)/L. All
      patients had prior TKI dose reductions. After the initiation of IL-11, 8 of 14
      patients (57%) had an increase in platelet count with a median peak platelet
      count of 110 x 10(9)/L. One additional patient had no platelet increase but was
      able to tolerate an imatinib dose increase. Eleven patients had a decrease in the
      number of days of TKI therapy interruption secondary to thrombocytopenia after
      the initiation of IL-11 (6% of total treatment time vs 34% of total treatment
      time before IL-11). Therapy was well tolerated. CONCLUSIONS: The current results
      indicated that IL-11 may correct thrombocytopenia associated with TKI therapy for
      patients with CML and that it has a favorable toxicity profile.

PMID- 18629843
TI  - Generation of flow cytometry data files with a potentially infinite number of
      dimensions.
AB  - Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders
      (B-CLPD) is associated with the use of increasingly larger panels of multiple
      combinations of 3 to > or =6 monoclonal antibodies (Mab), data analysis being
      separately performed for each of the different stained sample aliquots. Here, we
      describe and validate an automated method for calculation of flow cytometric data
      from several multicolor stainings of the same cell sample--i.e., the merging of
      data from different aliquots stained with partially overlapping combinations of
      Mab reagents (focusing on > or =1 cell populations)--into one data file as if it
      concerned a single "super" multicolor staining. Evaluation of the performance of
      the method described was done in a group of 60 B-CLPD studied at diagnosis with
      18 different reagents in a panel containing six different 3- and 4-color
      stainings, which systematically contained CD19 for the identification of B-cells.
      Our results show a high degree of correlation and agreement between originally
      measured and calculated data about cell surface stainings, providing a basis for
      the use of this approach for the generation of flow cytometric data files
      containing information about a virtually infinite number of stainings for each
      individual cellular event measured in a sample, using a limited number of
      fluorochrome stainings.

PMID- 18629844
TI  - Polychromatic plots: graphical display of multidimensional data.
AB  - Limitations of graphical displays as well as human perception make the
      presentation and analysis of multidimensional data challenging. Graphical display
      of information on paper or by current projectors is perforce limited to two
      dimensions; the encoding of information from other dimensions must be overloaded
      into the two physical dimensions. A number of alternative means of encoding this
      information have been implemented, such as offsetting data points at an angle
      (e.g., three-dimensional projections onto a two-dimensional surface) or
      generating derived parameters that are combinations of other variables (e.g.,
      principal components). Here, we explore the use of color to encode additional
      dimensions of data. PolyChromatic Plots are standard dot plots, where the color
      of each event is defined by the values of one, two, or three of the measurements
      for that event. The measurements for these parameters are mapped onto an
      intensity value for each primary color (red, green, or blue) based on different
      functions. In addition, differential weighting of the priority with which
      overlapping events are displayed can be defined by these same measurements.
      PolyChromatic Plots can encode up to five independent dimensions of data in a
      single display. By altering the color mapping function and the priority function,
      very different displays that highlight or de-emphasize populations of events can
      be generated. As for standard black-and-white dot plots, frequency information
      can be significantly biased by this display; care must be taken to ensure
      appropriate interpretation of the displays. PolyChromatic Plots are a powerful
      display type that enables rapid data exploration. By virtue of encoding as many
      as five dimensions of data independently, an enormous amount of information can
      be gleaned from the displays. In many ways, the display performs somewhat like an
      unsupervised cluster algorithm, by highlighting events of similar distributions
      in multivariate space.

PMID- 18629846
TI  - Biochemical engineering IX-interdisciplinary foundations for creating new
      biotechnology: I.

PMID- 18629847
TI  - Biological and physical factors influencing the successful engraftment of a
      cultured human skin substitute.
AB  - Skin tissue may be engineered in a variety of ways. Our cultured skin substitute
      (Graftskin, living skin equivalent or G-LSE), Apligraftrade mark, is an
      organotypic culture of skin, containing both a "dermis" and "epidermis." The
      epidermis is an important functional component of skin, responsible for biologic
      wound closure. The epidermis possesses a stratum corneum which develops with time
      in culture. The stratum corneum provides barrier function properties and gives
      the LSE improved strength and handling characteristics. Clinical experience
      indicated that the stratum corneum might play an important role in improving the
      clinical utility of the LSE. Handling and physical characteristics improved with
      time in culture. We examined the LSE at different stages of epidermal maturation
      for barrier function and ability to persist as a graft. LSE grafted onto athymic
      mice before significant development of barrier function did not withstand bandage
      removal at 7 days postgraft. LSE grafted after barrier function had been
      established in vitro were able to withstand bandage removal at day 7. Corneum
      lipid composition and structure are critical components for barrier function.
      Media modifications were used in an attempt to improve the fatty acid composition
      of the stratum corneum. The barrier developed more rapidly and was improved in a
      serum-free, lipid-supplemented condition. Lipid lamellar structure was improved
      with 10% of the stratum corneum exhibiting broad-narrow-broad lipid lamellar
      arrangements similar to human skin. Fatty acid metabolism was not appreciably
      altered. Barrier function in vitro was 4- to 10-fold more permeable than human
      skin. Epidermal differentiation does not compromise engraftment or the wound
      healing ability of the epidermis. The stratum corneum provides features
      beneficial for engraftment and clinical use. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629848
TI  - Enhanced function of cultured epithelium by genetic modification: Cell-based
      synthesis and delivery of growth factors.
AB  - Skin substitutes, containing cultured keratinocytes of the epidermis (autologous
      or allogeneic cells), have been used in the treatment of severe burns and other
      defects of the skin such as chronic ulcers. Our goal is to enhance the functions
      of the cells used in these skin substitutes by genetic modification. We propose
      to develop a genetically modified skin graft which would function as a cell-based
      vehicle for the local synthesis and delivery of wound-healing growth factors.
      Using retroviral-mediated gene transfer, we have introduced stable copies of the
      genes encoding platelet-derived growth factor (PDGF-A) or insulin-like growth
      factor-1 (IGF-1) into cultured human diploid keratinocytes. After stable
      integration of these genes, the cells secreted significant levels of these growth
      factors, 744 ng and 502 ng/10(7) cells/24 h for PDGF-A and IGF-1, respectively.
      The modified cells were grown to confluence, detached as a multicell-layered
      epithelial sheet, and transplanted to athymic mice.Seven days after
      transplantation, grafts secreting PDGF-A or IGF-1 differentiated into a
      stratified epithelium comparable to unmodified cells. Most importantly, the newly
      synthesized connective tissue layer subjacent to the PDGF-A-modified grafts was
      significantly thicker and showed an increase in cellularity, vascularity, type I
      collagen, and fibronectin deposition when compared to control grafts of
      unmodified cells or grafts expressing IGF-1.These results demonstrated that the
      function of the cells of a skin substitute can be enhanced by genetic
      modification and show that PDGF-A secretion from these cells can mediate changes
      to the cellular, vascular, and extracellular matrix composition of the adjacent
      dermal tissue. Moreover, these results suggest that a cell-based method for
      growth factor synthesis and delivery may be a useful approach to promoting tissue
      repair. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629849
TI  - Unilineage model of hematopoiesis predicts self-renewal of stem and progenitor
      cells based on ex vivo growth data.
AB  - Stem cell models are used to describe the function of several tissues. We present
      unilineage kinetic description of stem cell models and their application to the
      analysis of ex vivo hematopoietic cell expansion data. This model has the
      capability to simulate the total cell number and the number of cells at each
      stage of differentiation over time as a function of the stem cell self-renewal
      probability, the growth rate of each subpopulation, and the mature cell death
      rate. The model predicts experimental observations in perfusion-based
      hematopoietic bioreactor systems. To obtain net cell expansion ex vivo, the model
      simulations show that the stem cell self-renewal probability must exceed one
      half, thus resulting in net expansion of the stem cell population. Experimental
      data on long-term culture-initiating cells (LTC-IC) confirm this prediction and
      the probability of self-renewal is estimated to be 0.62 to 0.73. This self
      renewal probability, along with the death rate, define a relationship in which
      the apparent overall growth rate is less than the compartmental growth rate.
      Finally, the model predicts that cells beyond the stem cell stage of
      differentiation must self-renew to achieve the level of expansion within the time
      frame observed in experimental systems. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629850
TI  - Hollow fiber bioartificial liver utilizing collagen-entrapped porcine hepatocyte
      spheroids.
AB  - A xenogeneic hollow fiber bioreactor utilizing collagen-entrapped dispersed
      hepatocytes has been developed as an extracorporeal bioartificial liver (BAL) for
      potential treatment of acute human fulminant hepatitis. Prolonged viability,
      enhanced liver-specific functions, and differentiated state have been observed in
      primary porcine hepatocytes cultivated as spheroids compared to dispersed
      hepatocytes plated on a monolayer. Entrapment of spheroids into the BAL can
      potentially improve performance over the existing device. Therefore, studies were
      conducted to evaluate the feasibility of utilizing spheroids as the functionally
      active component of our hybrid device. Confocal microscopy indicated high
      viability of spheroids entrapped into cylindrical collagen gel. Entrapment of
      spheroids alone into collagen gel showed reduced ability to contract collagen
      gel. By mixing spheroids with dispersed cells, the extent of collagen gel
      contraction was increased. Hepatocyte spheroids collagen-entrapped into BAL
      devices were maintained for over 9 days. Assessment of albumin synthesis and
      ureagenesis within a spheroid-entrapment BAL indicated higher or at least as high
      activity on a per-cell basis compared to a dispersed hepatocyte-entrapment BAL
      device. Clearance of 4-methylumbelliferone to its glucuronide was detected
      throughout the culture period as a marker of phase II conjugation activity. A
      spheroid-entrapment bioartificial liver warrants further studies for potential
      human therapy. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629851
TI  - A self-regulating cell culture analog device to mimic animal and human
      toxicological responses.
AB  - The overall goal of this project is the development of a new methodology for
      translating advances in molecular level understanding of toxicological responses
      into a predictive tool for dose response in whole animals and humans exposed to
      single compounds or mixtures of compounds. The methodology incorporates a
      mechanistic cellular level model into a PBPK (physiologically based
      pharmacokinetic) model which simultaneously guides the development of an in vitro
      cell culture analog (CCA) to the PBPK. Where the PBPK specifies an organ, (e.g.,
      liver) the in vitro or CCA system contains a compartment with the appropriate
      cell or cell population (e.g., hepatocytes for the liver). The CCA has
      significant advantages over other in vitro systems and PBPK systems used
      independently for evaluating metabolic responses to drugs or potentially toxic
      chemicals where the exchange of metabolites between organs is likely to be
      important. The CCA system is superior to a PBPK because an a priori description
      of complete metabolism is not required and secondary, unexpected interactions can
      be detected. The CCA system, unlike other in vitro systems, gives a dynamic
      response that realistically simulates in vivo interactions between organs.
      Furthermore, the CCA allows dosing on the same basis as animal tests (e.g.,
      milligrams per kilogram of body mass equivalent). Because the construction of a
      CCA is guided by a PBPK, this approach allows extrapolation to low doses and
      across species, including extrapolation to humans. We have constructed a
      prototype system and have conducted proof-of-concept experiments using
      naphthalene as a test chemical. These experiments clearly demonstrate the ability
      to generate a reactive metabolite in one compartment and detect its effects (on
      LDH release and glutathione depletion) in a second compartment. However, this
      prototype device would be expensive to replicate and requires nearly constant
      supervision from a trained investigator. For this concept to replace animals an
      inexpensive, self-regulating device is needed. An initial design to accomplish
      this goal is described as well as the corresponding model using naphthalene as a
      test compound. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629852
TI  - Engineering dynamics of growth factors and other therapeutic ligands.
AB  - Peptide growth factors and other receptor-binding cytokine ligands are of
      interest in contemporary molecular health care approaches in applications such as
      wound healing, tissue regeneration, and gene therapy. Development of effective
      technologies based on operation of these regulatory molecules requires an ability
      to deliver the ligands to target cells in a reliable and well-characterizable
      manner. Quantitative information concerning the fate of peptide ligands within
      tissues is necessary for adequate interpretation of experimental observations at
      the tissue level and for truly rational engineering design of ligand-based
      therapies. To address this need, we are undertaking efforts to elucidate effects
      of key molecular and cellular parameters on temporal and spatial distribution of
      cytokines in cell population and cell/matrix systems. In this article we
      summarize some of our recent findings on dynamics of growth factor depletion by
      cellular endocytic trafficking, growth factor transport through cellular
      matrices, and growth factor production and release by autocrine cell systems. (c)
      1996 John Wiley & Sons, Inc.

PMID- 18629853
TI  - Platelet adhesion to polyurethane blended with polytetramethylene oxide.
AB  - The surface and blood compatibility characteristics of Pellethane polyurethane
      blended with 1% or 5% (w/w) polytetramethylene oxide (PTMO) were evaluated.
      Analysis by X-ray photoelectron spectroscopy indicated that blending of PTMO
      caused an increased amount of amide wax, a processing agent present in
      Pellethane, to be expressed on the surface of the blended films in vacuo. Dynamic
      contact angle measurements in water, however, showed that PTMO was preferentially
      expressed on the blend film surfaces in water. The two lower molecular weight
      species, PTMO and amide wax, were thus capable of reorienting, depending on the
      environmental conditions. An in vitro assay of platelet adherence and thrombosis
      showed that polyurethane blended with 5% PTMO had about two-thirds fewer adherent
      platelets compared to unblended polyurethane and that a blend containing 1% PTMO
      was intermediate in platelet adherence. Measurements of albumin adsorption from
      binary solution with fibrinogen indicated that PTMO blends did not preferentially
      adsorb albumin compared to unblended polyurethane. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18629854
TI  - Poly(organo phosphazene) nanoparticles surface modified with poly(ethylene
      oxide).
AB  - The use of biodegradable derivatives of poly(organo phosphazenes) for the
      preparation of nanoparticles and their surface modification with the novel
      poly(ethylene oxide) derivative of poly(organo phosphazene) has been assessed
      using a range of in vitro characterization methods. The nanoparticles were
      produced by the precipitation solvent evaporation method from the derivative co
      substituted with phenylalanine and glycine ethyl ester side groups. A reduction
      in particle size to less than 200 nm was achieved by an increase in pH of the
      preparation medium. The formation (and colloidal stability) of these
      nanoparticles seems to be controlled by two opposite effects: attractive
      hydrophobic interactions between phenylalanine ester groups and electrostatic
      repulsions arising from the carboxyl groups formed due to (partial) hydrolysis of
      the ester bond(s) at the high pH of the preparation medium. The poly[(glycine
      ethyl ester)phosphazene] derivative containing 5000-Da poly(ethylene oxide) as 5%
      of the side groups was used for the surface modification of nanoparticles.
      Adsorbed onto the particles, the polymer produced a thick coating layer of
      approximately 35 nm. The coated nanoparticles exhibited reduced surface negative
      potential and improved colloidal stability toward electrolyte-induced
      flocculation, relative to the uncoated system. However, the steric stabilization
      provided was less effective than that of a Poloxamine 908 coating. This
      difference in effectiveness of the steric stabilization might indicate that,
      although both the stabilizing polymers possess a 5000-Da poly(ethylene oxide)
      moiety, there is a difference in the arrangements of these poly(ethylene oxide)
      chains at the particle surface. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629855
TI  - Poly(fumaric-co-sebacic) microspheres as oral drug delivery systems.
AB  - The current study focuses on the development of bioadhesive oral delivery systems
      based on bioerodible polyanhydrides. The polymers were studied and characterized
      using a novel tensiometer based on a very sensitive electrobalance. The system
      was designed to mimic in vivo interactions, thus all experiments were conducted
      with freshly excised tissue immersed in physiological saline at 37 degrees C.
      Poly(fumaric-co-sebacic) [P(FA:SA)] was found to be the most bioadhesive polymer
      from a series of different thermoplastic materials evaluated. Correlation with in
      vivo performance was investigated by determining gastrointestinal (GI) residence
      time of barium-loaded microspheres. Residence times of 24 to 36 h provided a
      strong indication that these microspheres were good candidates for bioadhesive
      drug delivery systems. To evaluate the effect of these materials on
      bioavailability, the anticoagulant drug, dicumarol, was encapsulated. Systemic
      blood levels demonstrated increased bioavailability for the encapsulated
      dicumarol formulation as compared with unencapsulated drug. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18629856
TI  - Biomedical applications of degradable polyphosphazenes.
AB  - This article describes the synthesis of biodegradable polyphosphazenes. The rate
      of degradation can be varied in a controllable manner by the introduction of
      hydrolysis-sensitive amino acid ester side groups or by blending of polymers.
      Biodegradable polyphosphazenes can be used for the preparation of drug-containing
      implants and this is illustrated for devices containing the cytostatic agent
      mitomycin C. This article reviews data about the degradation characteristics of
      poly[(amino acid ester)phosphazene] derivatives that have been discussed
      previously. Some new data about MMC-containing poly[(organo)phosphazene] devices
      are discussed as well. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629857
TI  - Inverse metabolic engineering: A strategy for directed genetic engineering of
      useful phenotypes.
AB  - The classical method of metabolic engineering, identifying a rate-determining
      step in a pathway and alleviating the bottleneck by enzyme overexpression, has
      motivated much research but has enjoyed only limited practical success.
      Intervention of other limiting steps, of counterbalancing regulation, and of
      unknown coupled pathways often confounds this direct approach. Here the concept
      of inverse metabolic engineering is codified and its application is illustrated
      with several examples. Inverse metabolic engineering means the elucidation of a
      metabolic engineering strategy by: first, identifying, constructing, or
      calculating a desired phenotype; second, determining the genetic or the
      particular environmental factors conferring that phenotype; and third, endowing
      that phenotype on another strain or organism by directed genetic or environmental
      manipulation. This paradigm has been successfully applied in several contexts,
      including elimination of growth factor requirements in mammalian cell culture and
      increasing the energetic efficiency of microaerobic bacterial respiration. (c)
      1996 John Wiley & Sons, Inc.

PMID- 18629858
TI  - Evolutionally guided enzyme design.
AB  - A combination of "rational" and "irrational" strategies for the creation of
      enzymes with novel properties is proving to be a powerful concept in the field of
      enzyme engineering. Guided by principles of physical organic chemistry, rational
      design strategies are used to identify suitable target enzymes and to choose
      appropriate molecular biological methods for engineering purposes. In contrast,
      irrational (or random) strategies are centered around the biological paradigm of
      stochastic molecular evolution. As illustrated in this review, such a hybrid
      approach is particularly useful for the design of new modular enzymes. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18629859
TI  - Pathway analysis, engineering, and physiological considerations for redirecting
      central metabolism.
AB  - The rate and yield of producing a metabolite is ultimately limited by the ability
      to channel metabolic fluxes from central metabolism to the desired biosynthesis
      pathway. Redirection of central metabolism thus is essential to high-efficiency
      production of biochemicals. This task begins with pathway analysis, which
      considers only the stoichiometry of the reaction networks but not the regulatory
      mechanisms. An approach extended from convex analysis is used to determine the
      basic reaction modes, which allows the determination of optimal and suboptimal
      flux distributions, yield, and the dispensable sets of reactions. Genes
      responsible for reactions in the same dispensable set can be deleted
      simultaneously. This analysis serves as an initial guideline for pathway
      engineering. Using this analysis, we successfully constructed an Escherichia coli
      strain that can channel the metabolic flow from carbohydrate to the aromatic
      pathway with theoretical yield. This analysis also predicts a novel cycle
      involving phosphoenolpyruvate (PEP) carboxykinase (Pck) and the glyoxylate shunt,
      which can substitute the tricarboxylic acid cycle with only slightly less
      efficiency. However, the full cycle could not be confirmed in vivo, possibly
      because of the regulatory mechanism not considered in the pathway analysis.In
      addition to the kinetic regulation, we have obtained evidence suggesting that
      central metabolites are involved in specific regulons in E. coli. Overexpression
      of PEP-forming enzymes (phosphoenolpyruvate synthase [Pps] and Pck) stimulates
      the glucose consumption rate, represses the heat shock response, and negatively
      regulates the Ntr regulon. These results suggest that some glycolytic
      intermediates may serve as a signal in the regulation of the phosphotransferase
      system, heat shock response, and nitrogen regulation. However, the role of
      central metabolites in these regulations has not been determined conclusively.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18629860
TI  - Cybernetic modeling of growth in mixed, substitutable substrate environments:
      Preferential and simultaneous utilization.
AB  - Growth of microorganisms on substitutable substrate mixtures display diverse
      growth dynamics characterized by simultaneous or preferential uptake of carbon
      sources. This article shows that cybernetic modeling concepts which were
      successful in predicting diauxic growth patterns can be extended to describe
      simultaneous consumption of substrates. Thus the growth of Escherichia coli on
      mixtures of glucose and organic acids such as pyruvate, fumarate, and succinate
      has been described successfully by the cybernetic model presented here showing
      both diauxic and simultaneous uptake when observed. The model also describes the
      changes in utilization patterns that occur under changing dilution rates,
      substrate concentrations, and models of preculturing. The model recognizes the
      importance of the synthesis of biosynthetic precursors in cell growth through a
      kinetic structure that is quite general for any mixture of carbon-energy sources.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18629861
TI  - Effects of elevated pCO(2) and/or osmolality on the growth and recombinant tPA
      production of CHO cells.
AB  - Carbon dioxide is a by-product of mammalian cell metabolism that will build up in
      culture if it is not removed from the medium. Increased carbon dioxide levels are
      generally not a problem in bench-top bioreactors, but inhibitory levels can
      easily be reached in large-scale vessels, especially if the aeration gas is
      enriched in oxygen. Due to the equilibrium attained between dissolved CO(2) and
      bicarbonate, increased pCO(2) is associated with increased osmolality in
      bioreactors with pH control. While a few preliminary reports indicate that
      elevated pCO(2) levels can inhibit cell growth and/or recombinant protein
      production, no comprehensive analysis of the interrelated effects of elevated
      pCO(2) and osmolality has been published. We have examined the effects of 140,
      195, and 250 mm Hg (187, 260, and 333 mbar, respectively) pCO(2) (with and
      without osmolality control) on the growth of and recombinant tPA production by
      MT2-1-8 Chinese hamster ovary (CHO) cells. The effects of elevated osmolality
      were also investigated at the control pCO(2) of 36 mm Hg. Elevated pCO(2) at 310
      mOsm/kg osmolality inhibited cell growth in a dose-dependent fashion, with a
      maximum decrease of 30% in the specific growth rate (mu) at 250 mm Hg. Osmolality
      alone had no effect on mu, but the combination of elevated pCO(2) and osmolality
      increased the maximal reduction in mu to 45%. Elevated pCO(2) at 310 mOsm/kg
      osmolality decreased the specific tPA production rate (q(tPA)) by up to 40% at
      250 mm Hg. Interestingly, while increased osmolality decreased q(tPA)
      significantly at 140 mm Hg pCO(2), it had no effect or even increased q(tPA) at
      195 and 250 mm Hg. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629862
TI  - Role of glucose signaling in yeast metabolism.
AB  - In this article, knowledge concerning the relation between uptake of and
      signaling by glucose in the yeast Saccharomyces cerevisiae is reviewed and
      compared to the analogous process in prokaryotes. It is concluded that (much)
      more fundamental knowledge concerning these processes is required before rational
      redesign of metabolic fluxes from glucose in yeast can be achieved. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18629863
TI  - Enhancement of survivability of mammalian cells by overexpression of the
      apoptosis-suppressor gene bcl-2.
AB  - Cell lines derived from the hemopoetic lineages are widely used as hosts for the
      production of biologicals. These cell lines have been demonstrated to undergo
      high levels of the active death program commonly referred to as apoptosis. The
      effects of overexpression of the apoptosis suppressor gene bcl-2 on the
      properties of a Burkitt lymphoma were compared with the control cell line
      (transfected with a negative control plasmid) under a variety of conditions
      relevant to cell culture production technology. In stationary batch cultures,
      there was a clear reduction in both the rate of total cell death and the level of
      apoptosis during the decline phase of the bcl-2 transfected cell cultures as
      compared with that of the control cell cultures. Nutrient analysis revealed that
      the onset of death during the control cell cultures occurred following complete
      exhaustion of glutamine. However, the bcl-2 transfected cell cultures continued
      to grow even though glutamine had been exhausted, and a significant decline in
      viability only occurred when glucose had also been completely exhausted.When
      cells were cultured in suspension without prior adaptation, the bcl-2 transfected
      cells grew significantly better, suggesting that the bcl-2 gene protected the
      cells from apoptosis triggered by either the lack of substrate or the
      hydrodynamic environment. Fluorescence microscopy revealed that death of the
      control cells was almost entirely by apoptosis, whereas death was almost
      exclusively by necrosis in the delayed decline phase of the transfected cell
      cultures. In both instances, death occurred before total exhaustion of glucose
      and glutamine.The induction of apoptosis following growth arrest is a major
      impediment to the development of culture strategies that optimize specific
      productivity by reducing the growth rate. Results presented here suggest that
      suppression of apoptosis by bcl-2 under the condition of excess thymidine allows
      the maintenance of cells in a growth-arrested state for much longer than would
      otherwise be possible.When cells were transferred to a range of commercial serum
      free media, cell growth was, in all cases, much better for the bcl-2 transfected
      cell line. Moreover, when cells were cultivated in glutamine-free medium, the
      control cells exhibited a decrease in viable cell number within the first 24 h
      whereas, for the bcl-2 transfected cell cultures, viable cell number did not
      exhibit any clear decrease until after 75 h. Clearly, these results indicate that
      the metabolic engineering approach can be used to alter advantageously the
      survival and proliferative capacity of cells in cell culture environments. (c)
      1996 John Wiley & Sons, Inc.

PMID- 18629864
TI  - Uncoupling effect of nitrite during denitrification by Pseudomonas fluorescens:
      An in vivo (31)P-NMR study.
AB  - In vivo (31)P-NMR was used to investigate the basis for the inhibition of
      denitrification by nitrite accumulated endogenously by Pseudomonas fluorescens
      ATCC 17822 (biotype II) at pH 7.0. Cells were immobilized in kappa-carrageenan to
      obtain high cell concentrations in the NMR tube. Acetate and nitrate in two
      concentration ratios were supplied as electron donor and acceptor, respectively,
      to achieve different levels of nitrite accumulation. During denitrification,
      cells were able to maintain a pH gradient of approximately 0.4 to 0.5 units, but
      when nitrite accumulation reached values approximating 27 mM the transmembrane
      DeltapH collapsed sharply. Nitrite stimulated the reduction rate of nitrate;
      furthermore, at nitrite concentrations below 1 mM, activation of oxygen
      respiratory rates was observed in cells grown under aerobic conditions. The
      results provide evidence for nitrite acting as a protonophore (an uncoupler that
      increases the proton permeability of membranes by a shuttling mechanism). (c)
      1996 John Wiley & Sons, Inc.

PMID- 18629865
TI  - Palatal seam disintegration: to die or not to die? that is no longer the
      question.
AB  - Formation of the medial epithelial seam (MES) by palatal shelf fusion is a
      crucial step of palate development. Complete disintegration of the MES is the
      final essential phase of palatal confluency with surrounding mesenchymal cells.
      In general, the mechanisms of palatal seam disintegration are not overwhelmingly
      complex, but given the large number of interacting constituents; their
      complicated circuitry involving feedforward, feedback, and crosstalk; and the
      fact that the kinetics of interaction matter, this otherwise simple mechanism can
      be quite difficult to interpret. As a result of this complexity, apparently
      simple but highly important questions remain unanswered. One such question
      pertains to the fate of the palatal seam. Such questions may be answered by
      detailed and extensive quantitative experimentation of basic biological studies
      (cellular, structural) and the newest molecular biological determinants
      (genetic/dye cell lineage, gene activity, kinase/enzyme activity), as well as
      animal model (knockouts, transgenic) approaches. System biology and cellular
      kinetics play a crucial role in cellular MES function; omissions of such critical
      contributors may lead to inaccurate understanding of the fate of MES. Excellent
      progress has been made relevant to elucidation of the mechanism(s) of palatal
      seam disintegration. Current understanding of palatal seam disintegration
      suggests epithelial-mesenchymal transition and/or programmed cell death as two
      most common mechanisms of MES disintegration. In this review, I discuss those two
      mechanisms and the differences between them.

PMID- 18629867
TI  - Role for primary cilia in the regulation of mouse ovarian function.
AB  - Ift88 is a component of the intraflagellar transport complex required for
      formation and maintenance of cilia. Disruption of Ift88 results in depletion of
      cilia. The goal of the current study was to determine the role of primary cilia
      in ovarian function. Deletion of Ift88 in ovary using Cre-Lox recombination in
      mice resulted in a severe delay in mammary gland development including lack of
      terminal end bud structures, alterations in the estrous cycle, and impaired
      ovulation. Because estrogen drives the formation of end buds and Cre was
      expressed in the granulosa cells of the ovary, we tested the hypothesis that
      addition of estradiol to the mutant mice would compensate for defects in ovarian
      function and rescue the mammary gland phenotype. Mammary gland development
      including the formation of end bud structures resumed in mutant mice that were
      injected with estradiol. Together the results suggest that cilia are required for
      ovarian function.

PMID- 18629866
TI  - Morphogenesis of the node and notochord: the cellular basis for the establishment
      and maintenance of left-right asymmetry in the mouse.
AB  - Establishment of left-right asymmetry in the mouse embryo depends on leftward
      laminar fluid flow in the node, which initiates a signaling cascade that is
      confined to the left side of the embryo. Leftward fluid flow depends on two
      cellular processes: motility of the cilia that generate the flow and
      morphogenesis of the node, the structure where the cilia reside. Here, we provide
      an overview of the current understanding and unresolved questions about the
      regulation of ciliary motility and node structure. Analysis of mouse mutants has
      shown that the motile cilia must have a specific structure and length, and that
      they must point posteriorly to generate the necessary leftward fluid flow.
      However, the precise structure of the motile cilia is not clear and the
      mechanisms that position cilia on node cells have not been defined. The mouse
      node is a teardrop-shaped pit at the distal tip of the early embryo, but the
      morphogenetic events that create the mature node from cells derived from the
      primitive streak are only beginning to be characterized. Recent live imaging
      experiments support earlier scanning electron microscopy (SEM) studies and show
      that node assembly is a multi-step process in which clusters of node precursors
      appear on the embryo surface as overlying endoderm cells are removed. We present
      additional SEM and confocal microscopy studies that help define the transition
      stages during node morphogenesis. After the initiation of left-sided signaling,
      the notochordal plate, which is contiguous with the node, generates a barrier at
      the embryonic midline that restricts the cascade of gene expression to the left
      side of the embryo. The field is now poised to dissect the genetic and cellular
      mechanisms that create and organize the specialized cells of the node and midline
      that are essential for left-right asymmetry.

PMID- 18629868
TI  - Characterization of primary cilia and Hedgehog signaling during development of
      the human pancreas and in human pancreatic duct cancer cell lines.
AB  - Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant
      Hh signaling is associated with several pancreatic diseases. Here we investigated
      the link between Hh signaling and primary cilia in the human developing
      pancreatic ducts and in cultures of human pancreatic duct adenocarcinoma cell
      lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human
      embryogenesis to fetal development is associated with accumulation of Hh
      signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3
      in the duct epithelium. Smo, Ptc, and Gli2 localized to primary cilia of PANC-1
      and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway
      activity. These findings indicate that primary cilia are involved in pancreatic
      development and postnatal tissue homeostasis.

PMID- 18629869
TI  - Formation of the asymmetric pineal complex in zebrafish requires two
      independently acting transcription factors.
AB  - The pineal complex of zebrafish consists of a pineal organ and a left-sided
      parapineal organ. Mutation of the floating head (flh) gene, which encodes a
      homeodomain protein, causes premature termination of pineal cell division without
      affecting specification or asymmetric placement of the parapineal. The from
      beyond (fby) mutation, a premature stop codon in the T-domain-containing protein
      Tbx2b, disrupts formation of the parapineal while leaving the pineal largely
      intact. However, flh is reported as being required for tbx2b transcription. To
      resolve the paradox that flhand tbx2b mutants have opposite phenotypes but have
      been placed in the same genetic pathway, we have examined transcriptional cross
      regulation in single flh or fby mutants and genetic epistasis in double mutants.
      Careful analysis shows that flh is not required for tbx2b transcription and
      double mutants exhibit an additive phenotype. We conclude that Flh and Tbx2b
      regulate separate programs of pineal and parapineal development.

PMID- 18629870
TI  - Reprogramming multipotent tumor cells with the embryonic neural crest
      microenvironment.
AB  - The embryonic microenvironment is an important source of signals that program
      multipotent cells to adopt a particular fate and migratory path, yet its
      potential to reprogram and restrict multipotent tumor cell fate and invasion is
      unrealized. Aggressive tumor cells share many characteristics with multipotent,
      invasive embryonic progenitors, contributing to the paradigm of tumor cell
      plasticity. In the vertebrate embryo, multiple cell types originate from a highly
      invasive cell population called the neural crest. The neural crest and the
      embryonic microenvironments they migrate through represent an excellent model
      system to study cell diversification during embryogenesis and phenotype
      determination. Recent exciting studies of tumor cells transplanted into various
      embryo models, including the neural crest rich chick microenvironment, have
      revealed the potential to control and revert the metastatic phenotype, suggesting
      further work may help to identify new targets for therapeutic intervention
      derived from a convergence of tumorigenic and embryonic signals. In this mini
      review, we summarize markers that are common to the neural crest and highly
      aggressive human melanoma cells. We highlight advances in our understanding of
      tumor cell behaviors and plasticity studied within the chick neural crest rich
      microenvironment. In so doing, we honor the tremendous contributions of Professor
      Elizabeth D. Hay toward this important interface of developmental and cancer
      biology.

PMID- 18629871
TI  - Live imaging of cell protrusive activity, and extracellular matrix assembly and
      remodeling during morphogenesis in the frog, Xenopus laevis.
AB  - Cell motility and matrix assembly have traditionally been studied in isolation
      because of a lack of suitable model systems in which both can be observed
      simultaneously. With embryonic tissues from the gastrulating frog Xenopus laevis
      we observe stages of fibronectin fibrillogenesis coincident with protrusive
      activity in the overlying cells. Using live confocal time-lapse images collected
      from Cy3-tagged fibronectin and plasma membrane tethered green fluorescent
      protein, we describe the movement and the elaboration of a complex fibrillar
      network undergoing topological rearrangements of fibrils on the surface of an
      embryonic tissue. Discrete processes of annealing, polymerization, stretching,
      breaking, and recoiling are recorded. Elaboration and maintenance of the complex
      topology of the extracellular matrix appears to require filamentous actin. These
      findings support a mechanical-model in which cell tractive forces elaborate the
      complex topological fibrillar network and are part of a homeostatic mechanism for
      the regulation of the extracellular matrix.

PMID- 18629874
TI  - A combined ab initio and Franck-Condon factor simulation study on the
      photodetachment spectrum of ScO2(-).
AB  - Restricted-spin coupled-cluster single-double plus perturbative triple excitation
      {RCCSD(T)} potential energy functions (PEFs) of the X(2)B2 state of ScO2 and the
      1A1 state of ScO2(-) were computed, employing the augmented correlation
      consistent polarized-weighted core-valence quadruple-zeta (aug-cc-pwCVQZ) basis
      set for Sc and augmented correlation-consistent polarized valence quadruple-zeta
      (aug-cc-pVQZ) basis set for O, and with the outer core Sc 3s(2)3p(6) electrons
      being explicitly correlated. Franck-Condon factors, which include allowance for
      Duschinsky rotation and anharmonicity, were calculated using the computed
      RCCSD(T) PEFs, and were used to simulate the first photodetachment band of ScO2(
      ). The simulated spectrum matches well with the corresponding experimental 355 nm
      photodetachment spectrum of Wu and Wang, J Phys Chem A 1998, 102, 9129,
      confirming the assignment of the photodetachment spectrum and the reliability of
      the RCCSD(T) PEFs used. Further calculations on low-lying electronic states of
      ScO2 gave adiabatic relative electronic energies (T(e)'s) of, and vertical
      excitation energies (T(v)'s) to, the 2A1, 2B1, and 2A2 states of ScO2 (from the
      X(2)B2 state of ScO2), as well as electron affinities (EAs) and vertical
      detachment energies (VDEs) to these neutral states from the 1A1 state of ScO2(-).

PMID- 18629872
TI  - Altered endochondral ossification in collagen X mouse models leads to impaired
      immune responses.
AB  - Disruption of collagen X function in hypertrophic cartilage undergoing
      endochondral ossification was previously linked to altered hematopoiesis in
      collagen X transgenic (Tg) and null (KO) mice (Jacenko et al., [2002] Am J Pathol
      160:2019-2034). Mice displayed altered growth plates, diminished trabecular bone,
      and marrow hypoplasia with an aberrant lymphocyte profile throughout life. This
      study identifies altered B220+, CD4+, and CD8+ lymphocyte numbers, as well as
      CD4+/fox3P+ T regulatory cells in the collagen X mice. Additionally, diminished
      in vitro splenocyte responses to mitogens and an inability of mice to survive a
      challenge with Toxoplasma gondii, confirm impaired immune responses. In concert,
      ELISA and protein arrays identify aberrant levels of inflammatory, chemo
      attractant, and matrix binding cytokines in collagen X mouse sera. These data
      link the disruption of collagen X function in the chondro-osseous junction to an
      altered hematopoietic stem cell niche in the marrow, resulting in impaired immune
      function.

PMID- 18629875
TI  - Subtelomeric 6p deletion: clinical and array-CGH characterization in two
      patients.
AB  - We report on two patients with de novo subtelomeric terminal deletion of
      chromosome 6p. Patient 1 is an 8-month-old female born with normal growth
      parameters, typical facial features of 6pter deletion, bilateral corectopia, and
      protruding tongue. She has severe developmental delay, profound bilateral
      neurosensory deafness, poor visual contact, and hypsarrhythmia since the age of 6
      months. Patient 2 is a 5-year-old male born with normal growth parameters and
      unilateral hip dysplasia; he has a characteristic facial phenotype, bilateral
      embryotoxon, and moderate mental retardation. Further characterization of the
      deletion, using high-resolution array comparative genomic hybridization (array
      CGH; Agilent Human Genome kit 244 K), revealed that Patient 1 has a 8.1 Mb 6pter
      6p24.3 deletion associated with a contiguous 5.8 Mb 6p24.3-6p24.1 duplication and
      Patient 2 a 5.7 Mb 6pter-6p25.1 deletion partially overlapping with that of
      Patient 1. Complementary FISH and array analysis showed that the inv del dup(6)
      in Patient 1 originated de novo. Our results demonstrate that simple
      rearrangements are often more complex than defined by standard techniques. We
      also discuss genotype-phenotype correlations including previously reported cases
      of deletion 6p.

PMID- 18629876
TI  - The CASK gene harbored in a deletion detected by array-CGH as a potential
      candidate for a gene causative of X-linked dominant mental retardation.
AB  - Here we report on a 5-year-old Japanese girl with developmental delay and
      microcephaly. Although she had a normal karyotype, a bacterial artificial
      chromosome-based array-comparative genome hybridization analysis detected a de
      novo 4.0-Mb heterozygous deletion at Xp11.3-p11.4 harboring nine genes. By
      comparison with a healthy carrier mother of a boy with atypical Norrie disease
      having a smaller deletion in the same region, we excluded four genes as
      candidates whose haploinsufficiency would be causative for developmental delay.
      Among the other five genes, CASK seems to be the most likely candidate for a
      causative gene, because it is strongly expressed in fetal brain and plays
      important roles in neural development and synaptic function. We confirmed that
      the expression of CASK mRNA was decreased in the patient compared with healthy
      controls and the patient's X-chromosomal inactivation was not skewed. These
      results suggested that the genetic deletion of CASK results in
      haploinsufficiency, which might be causative for the patient's developmental
      delay or mental retardation. (c) 2008 Wiley-Liss, Inc.

PMID- 18629877
TI  - Genetic disorders associated with macrocephaly.
AB  - Macrocephaly is associated with many genetic disorders and is a frequent cause of
      referral to the clinical geneticist. In this review we classify the commonly
      encountered macrocephaly disorders into useful categories and summarize recent
      genetic advances. Conditions where macrocephaly is a predominant aspect of the
      clinical presentation are discussed and a diagnostic approach to the common
      macrocephaly disorders is provided. Some emphasis is placed on familial
      macrocephaly (sometimes referred to as benign external hydrocephalus) and on the
      macrocephaly associated with autism spectrum disorders. The more recent
      conditions associated with the leukodystrophies and the organic acidurias are
      reviewed, but the well known conditions involving storage disorders and bone
      dysplasias are mentioned but not discussed. The genetic macrocephaly conditions
      cover a broad spectrum of gene disorders and their related proteins have diverse
      biological functions. As of yet it is not clear what precise biological pathways
      lead to generalized brain overgrowth.

PMID- 18629878
TI  - Pierre Robin sequence associated with first trimester fetal tamoxifen exposure.
AB  - Tamoxifen is a nonsteroidal antiestrogen used as the current adjuvant endocrine
      treatment of choice for premenopausal women treated for breast cancer and its
      potential for causing fetal harm during pregnancy remains inconclusive. While the
      evidence of tamoxifen's effects on humans in utero is minimal, animal studies
      have shown evidence of teratogenicity, hence the FDA's class D categorization of
      the drug. In 1994 Cullins et al. published a case report entitled "Goldenhar's
      Syndrome Associated with Tamoxifen Given to the Mother During Gestation." At the
      time of publication, the authors noted that the manufacturer of tamoxifen knew of
      two cases associated with tamoxifen administration which resulted in congenital
      craniofacial defects. Cullins' case of Goldenhar syndrome is also a craniofacial
      disorder and thus represented the third such case. We report on the fourth case
      of a tamoxifen-associated craniofacial anomaly. The mother became pregnant while
      undergoing tamoxifen therapy for breast cancer. A child with severe micrognathia
      and cleft palate was born. It is noteworthy that the two patterns of craniofacial
      malformations in tamoxifen exposed infants--Goldenhar syndrome in Cullins' et al.
      case and Pierre Robin sequence reported here--have also both been observed in
      isotretinoin exposed infants. While a larger spectrum of anomalies is
      characteristic of retinoic acid embryopathy, the specific craniofacial anomalies
      include facial asymmetry, microtia, micrognatha and U-shaped cleft of the
      secondary palate, that is, malformations seen in the two tamoxifen exposed
      infants. Therefore, it is conceivable that these two agents could produce
      comparable embryotoxic effects if they function in a like way during
      embryogenesis. While the majority of tamoxifen exposed infants are normal, the
      ascertainment of teratogenic effects from tamoxifen will best be determined by
      data from teratogen registries.

PMID- 18629879
TI  - An efficient algorithm for energy gradients and orbital optimization in valence
      bond theory.
AB  - An efficient algorithm for energy gradients in valence bond theory with
      nonorthogonal orbitals is presented. A general Hartree-Fock-like expression for
      the Hamiltonian matrix element between valence bond (VB) determinants is derived
      by introducing a transition density matrix. Analytical expressions for the energy
      gradients with respect to the orbital coefficients are obtained explicitly, whose
      scaling for computational cost is m(4), where m is the number of basis functions,
      and is thus approximately the same as in HF method. Compared with other existing
      approaches, the present algorithm has lower scaling, and thus is much more
      efficient. Furthermore, the expression for the energy gradient with respect to
      the nuclear coordinates is also presented, and it provides an effective algorithm
      for the geometry optimization and the evaluation of various molecular properties
      in VB theory. Test applications show that our new algorithm runs faster than
      other methods.

PMID- 18629873
TI  - Heparan sulfate proteoglycans: a GAGgle of skeletal-hematopoietic regulators.
AB  - This review summarizes our current understanding of the presence and function of
      heparan sulfate proteoglycans (HSPGs) in skeletal development and hematopoiesis.
      Although proteoglycans (PGs) comprise a large and diverse group of cell surface
      and matrix molecules, we chose to focus on HSPGs owing to their many proposed
      functions in skeletogenesis and hematopoiesis. Specifically, we discuss how HSPGs
      play predominant roles in establishing and regulating niches during skeleto
      hematopoietic development by participating in distinct developmental processes
      such as patterning, compartmentalization, growth, differentiation, and
      maintenance of tissues. Special emphasis is placed on our novel hypothesis that
      mechanistically links endochondral skeletogenesis to the establishment of the
      hematopoietic stem cell (HSC) niche in the marrow. HSPGs may contribute to these
      developmental processes through their unique abilities to establish and mediate
      morphogen, growth factor, and cytokine gradients; facilitate signaling; provide
      structural stability to tissues; and act as molecular filters and barriers.

PMID- 18629880
TI  - Compound heterozygosity for GDF5 in Du Pan type chondrodysplasia.
AB  - Du Pan type chondrodysplasia (DPC) represents the milder end of homozygous growth
      differentiation factor 5 (GDF5) disorders. We report on a 20-month-old child with
      complex brachydactyly and mild proximal fibular hypoplasia, consistent with DPC,
      in the absence of other anomalies of long bones and joints. Mutational analysis
      disclosed two novel GDF5 mutations within the protein's mature domain and in the
      cleavage site of the prodomain which explains the distinct DPC phenotype found in
      this patient. The unaffected mother and the father who presented with mild
      brachybaso/mesophalangy of all digits were both heterozygous carriers.

PMID- 18629881
TI  - Sacral appendage in a child with an FGFR2 mutation: a report and review.

PMID- 18629882
TI  - Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1.
AB  - Brachydactyly type A1 is a limb malformation characterized by a uniform
      shortening of the middle phalanges in all digits. Mutations in the Indian
      hedgehog (IHH) gene were shown to be the cause of this autosomal dominant
      disorder. The IHH protein is known to be an important signaling molecule involved
      in chondrocyte formation. So far, only missense mutations in IHH have been
      reported to cause BrachydactylyA1. We report here on the first deletion in IHH,
      p.delE95, causing mild BrachydactylyA1 in a small Dutch family. This brings the
      total number of different mutations found to cause BDA1 to 7.

PMID- 18629883
TI  - Clinical phenotype correlates to glycoprotein phenotype in a sib pair with CDG
      Ia.
AB  - Congenital disorder of glycosylation (CDG) type Ia (PMM2 mutations) is the most
      common genetic disorder of protein N-glycosylation. The wide clinical spectrum
      with mild to severe impairment of neurological function and extensive allelic
      heterogeneity hamper phenotype-genotype comparison. We report on two male adult
      siblings with the PMM2 mutations c. 385G > A (p.V129M) and c. 422G > A (p.R141H)
      and partially different clinical phenotype. Patient 2 has a more severe degree of
      neurological and systemic involvement and a more pronounced decrease in levels of
      serum glycoproteins. MALDI-TOF mass spectrometry of serum transferrin and alpha-1
      antitrypsin shows more pronounced glycosylation defects in the more severely
      affected patient. Glycoproteomic analysis may reveal differences in CDG-Ia
      patients with different disease severity and might endorse clinical
      characterization of CDG-Ia patients.

PMID- 18629884
TI  - Array-CGH in a series of 30 patients with mental retardation, dysmorphic
      features, and congenital malformations detected an interstitial 1p22.2-p31.1
      deletion in a patient with features overlapping the Goldenhar syndrome.
AB  - Genosensor Array 300 (Abbott) is a multiplex platform for array-based comparative
      genomic hybridization that detects unbalanced genomic aberrations including whole
      chromosome gains/losses, microdeletions, duplications and unbalanced subtelomeric
      rearrangements. A series of 30 patients with unexplained mental retardation,
      dysmorphic features, congenital abnormalities and normal high resolution
      karyotype and FISH subtelomeric studies were analyzed using Genosensor Array 300
      array-CGH. We identified a chromosomal aberration in one patient with an
      interstitial 1p31.1 deletion. FISH analysis with BACs specific probes of the 1p
      region confirmed the interstitial 1p22.2-p31.1 deletion. The patient was a 20
      year-old man with short stature, facial dysmorphism including asymmetry,
      scoliosis, severe psychomotor delay and an epibulbar dermoid cyst. The phenotype
      was compatible with Goldenhar syndrome despite the absence of asymmetric ears.
      This observation is of interest since it could be a clue in the search for the
      genes responsible for Goldenhar syndrome. This study demonstrates the utility of
      the array-CGH technology in detecting interstitial deletions.

PMID- 18629886
TI  - Biochemical engineering IX-interdisciplinary foundations for creating new
      biotechnology: II.

PMID- 18629887
TI  - Novel bioseparations using two-phase aqueous micellar systems.
AB  - We review our recent experimental and theoretical work aimed at investigating the
      potential use of two-phase aqueous micellar systems for the separation or
      concentration of hydrophilic biomaterials using the principle of liquid-liquid
      extraction. The systems studied include (1) a two-phase aqueous micellar system
      composed of the nonionic surfactant n-decyl tetra(ethylene oxide) (C(10)E(4)) and
      (2) a two-phase aqueous micellar system composed of the zwitterionic surfactant
      dioctanoyl phosphatidyl-choline (C(8)-lecithin). The experimental partitioning
      behavior of several hydrophilic proteins, including cytochrome (c), soybean
      trypsin inhibitor, ovalbumin, bovine serum albumin, and catalase, in two-phase
      aqueous C(10)E(4) and C(8)-lecithin micellar systems is reviewed. A theoretical
      formulation of the protein partitioning behavior, based on a description of
      excluded-volume interactions between the hydrophilic proteins and the micelles,
      is also reviewed. The theoretically predicted protein partitioning behavior is
      compared with that observed experimentally and is found to be in good agreement.
      The results of our investigation suggest that two-phase aqueous micellar systems
      of the type examined in this article are indeed potentially useful as extractant
      phases for the separation or concentration of proteins and other biomaterials.

PMID- 18629888
TI  - Self-interaction chromatography: a tool for the study of protein-protein
      interactions in bioprocessing environments.
AB  - We describe a new protein characterization technique called self-interaction
      chromatography (SIC), which exploits the specificity of protein-protein
      interactions that is common to protein aggregates and enables the rapid screening
      of protein formulation additives as physical stabilizers against aggregation.
      This technique also enables the identification of specific interaction sites and
      the determination of their relative importance for self-association. Mannitol,
      glycine, and dextran 40 were tested for their stabilizing effect toward the model
      protein lysozyme. Dextran 40 exhibited a poor stabilizing effect. While mannitol
      stabilized both the native and acid-denatured forms of lysozyme, glycine
      stabilized the native form with respect to the denatured species. These results
      are in good agreement with findings in the formulation literature. The SIC shows
      tremendous potential as a rapid formulation development tool. We also screened
      two putative interaction sites for involvement in the self-association of
      lysozyme and estimated the associated binding energies using a binding isotherm
      model that we developed. The sites screened consisted of residues 41-48 and 125
      128 and were selected based on their apparent importance in forming crystal
      contacts in several different crystal forms of lysozyme. Of the two sites, only
      residues 125-128 were found to influence self-association under the conditions we
      employed. Because the success of this technique depends on the exploitation of
      self-interactions between native species, several important applications are also
      suggested such as separating native from misfolded or variant species and probing
      site utilization in aggregation versus crystallization phenomena.

PMID- 18629889
TI  - Optimization of affinity and ion-exchange chromatographic processes for the
      purification of proteins.
AB  - This study documents several alternative approaches for the optimization of the
      ion-exchange and affinity chromatographic purification of proteins. In these
      approaches, the chromatographic process has been treated as a four-stage
      (adsorption, washing, elution, and regeneration) operation. Central to these
      investigations has been the elaboration of practical iterative procedures based
      on the use of theoretical models describing each of these stages. Predictions
      derived from these models have then been evaluated in terms of experimental data
      obtained using batch adsorption measurements in finite bath configurations and
      frontal breakthrough measurements with packed beds of different dimensions,
      containing nonporous and porous adsorbents of different selectivities and
      capacities for proteins. Commencing with the kinetic and distribution parameters
      derived from batch equilibrium measurements, the effect of the initial
      concentration of the target protein, the solid-liquid volume ratio, the
      superficial velocity and the column dimensions on the pressure drop, production
      rate, concentration profile, column utilization, and yield have been determined
      with packed beds. The potential of these iterative approaches to simplify the
      determination of key mass transfer and interaction parameters required for scale
      up and economic optimization of chromatographic purifications of proteins has
      been examined using ion exchange, immobilized metal ion affinity, and triazine
      dye pseudo-affinity adsorbents of different selectivity and adsorption
      capacities.

PMID- 18629890
TI  - Fundamental questions in optimizing ion-exchange chromatography of proteins using
      computer-aided process design.
AB  - The major objectives for preparative protein chromatography are maximal loading
      and increased flow rate while maintaining defined resolution. Conventionally a
      series of chromatographic experiments are performed and the optimal conditions
      are selected according to the separation criteria. Computer-aided process design
      uses the same strategy, except a group of related experiments are generated by
      computer simulation. The access to concrete separation parameters for valid
      simulation necessitates chromatographic experiments. Optimal conditions are
      determined in the same manner as conducted in the conventional strategy. Beside
      other parameters, the distribution coefficient (K) determines the performance of
      a chromatographic purification under overloading conditions. In ion-exchange
      chromatography the distribution coefficient is strongly influenced by the protein
      concentration (C) and the salt concentration (I). A strategy to derive the
      distribution coefficient from chromatographic experiments, such as isocratic runs
      (pulse response), linear gradients, and frontal analysis, is described and
      compared to previously published strategies. In ion-exchange chromatography, the
      number of plates and transfer units change with the salt concentration. The
      distribution coefficient for salt also changes under various conditions including
      salt and protein concentration. The number of plates and transfer units also vary
      with the flow rate. Furthermore criteria such as the multicomponent situation
      require a more complex mathematical treatment. Several solutions have been
      validated to circumvent those obstacles.

PMID- 18629891
TI  - Semi-on-line analysis for fast and precise monitoring of bioreaction processes.
AB  - Monitoring of substrates and products during fermentation processes can be
      achieved either by on-line, in situ sensors or by semi-on-line analysis
      consisting of an automatic sampling step followed by an ex situ analysis of the
      retrieved sample. The potential risk of introducing time delays and signal bias
      during sampling makes it necessary to distinguish between real-time, on-line, in
      situ methods and semi-on-line analysis. In addition, semi-on-line analyzers are
      often mechanically complex--a circumstance which has to be given special
      attention during their industrial use on a routine basis. This review on semi-on
      line analysis will focus both on the dynamics and precision of aseptic sampling
      devices and on the performance of flow injection analysis (FIA) and sequential
      injection analysis (SIA), especially with regard to their robustness when used in
      industry.

PMID- 18629892
TI  - Fluid dynamics in bubble column bioreactors: experiments and numerical
      simulations.
AB  - Detailed measurements of multiphase flows that prevail in bioreactors tell us
      that different transport mechanisms are dominating on different observation
      scales. The consequence in terms of reactor modeling is that the processes on
      different scales can be treated independently. A three-dimensional, dynamical
      model is presented that can be used to describe bubble column bioreactors on the
      reactor scale. It is based on the Navier-Stokes equation system. On the next
      smaller scale, the dynamics of the gas phase is described in a Lagrangian way, by
      tracking many bubble clusters or bubbles simultaneously on their way through the
      reactor. The model is capable of describing bubble columns of different size and
      can thus be used for scale-up. Its performance is demonstrated with a production
      scale beer fermentor.

PMID- 18629893
TI  - Capillary electrophoresis of DNA in uncrosslinked polymer solutions: evidence for
      a new mechanism of DNA separation.
AB  - The electrophoretic separation of DNA molecules is usually performed in thin
      slabs of agarose or polyacrylamide gel. However, DNA separations can be achieved
      more rapidly and efficiently within a microbore fused silica capillary filled
      with an uncrosslinked polymer solution. An early assumption was that the
      mechanism of DNA separation in polymer solution-capillary electrophoresis (PS-CE)
      is the same as that postulated to occur in slab gel electrophoresis, i.e., that
      entangled polymer chains form a network of "pores" through which the DNA
      migrates. However, we have demonstrated that large DNA restriction fragments (2.0
      23.1 kbp) can be separated by CE in extremely dilute polymer solutions, which
      contain as little as 6 parts per million [0.0006% (w/w)] of uncrosslinked
      hydroxyethyl cellulose (HEC) polymers. In such extremely dilute HEC solutions,
      far below the measured polymer entanglement threshold concentration, pore-based
      models of DNA electrophoresis do not apply. We propose a transient entanglement
      coupling mechanism for the electrophoretic separation of DNA in uncrosslinked
      polymer solutions, which is based on physical polymer/DNA interactions.

PMID- 18629894
TI  - Monitoring and control of the physiological state of cell cultures.
AB  - Advances in bioprocess engineering depends ultimately on the level of
      understanding and control of the physiological state of the cell population.
      Process efficiency is strongly influenced by changes in the cellular state which
      should be monitored, interpreted, and, if possible, properly manipulated. In most
      control systems this function is not explicitly considered, which hampers process
      development and optimization. Conventional control logic is based on direct
      mapping of the growth environment into process efficiency, thereby bypassing the
      cell state as an intermediate control objective. Today, this limitation is well
      realized, and explicit monitoring and control of cellular physiology are
      considered to be among the most challenging tasks of modern bioprocess
      engineering. We present here a generic methodology for the design of systems
      capable of performing these advanced monitoring and control functions.The term
      "physiological state" is quantified by a vector composed of several process
      variables that convey significant information about cellular state. These
      variables can be selected among different classes, including specific metabolic
      rates, metabolic rate ratios, degees of limitation, and others. The real-time
      monitoring of many of these is possible using commercial sensors. The definition
      and calculation of representative sets of physiological state variables is
      demonstrated with examples from several fermentor cultures: recombinant
      Escherichia coli for phenylalanine production, bioluminescent E. coli (harboring
      lux genes driven by a heat shock protein promoter) for detection of environmental
      pollutants, plant cell culture of Perilla frutescensfor anthocyanin production,
      and perfusion cultures of recombinant mammalian cells (NS0 and CHO) for
      therapeutic protein production.If the physiological state vector is on-line
      calculated, the fermentation process can be described by its trajectory in a
      space defined by the vector components. Then, the goal of the control system is
      to maintain the physiological state of the cell as close as possible to the
      trajectory, providing maximum efficiency. A control structure meant to perform
      this function is proposed, along with the mechanism for its design. In contrast
      to conventional systems which work in a closed loop in respect to the cell
      environment, this scheme operates in a closed loop in respect to the cell state.
      The discussed control concept has been successfully applied to the recombinant
      phenylalanine production, resulting in physiologically consistent operation,
      total computer control, and high process efficiency. Initial results from the
      application of the method to perfusion mammalian cell cultures are also
      presented.

PMID- 18629895
TI  - Chemical versus biochemical conversion: when and how to use biocatalysts.
AB  - Developments in biotechnology have been extremely rapid the last two decades.
      This is particularly true for recombinant DNA technology, which has strongly
      stimulated the study of biocatalysis, and many examples of new applications of
      biocatalysts exist. Nevertheless, they have not yet been routinely applied in
      chemistry. In this study, the question is addressed as to when biocatalysts can
      be advantageously used in this field. If that is indeed the case, many decisions
      have to be made before they can be optimally utilized. In the present work, a
      decision tree is introduced which provides important questions to answer to come
      to such an optimal use. Examples are given to illustrate the decision making.

PMID- 18629896
TI  - Extraordinary enantiospecificity of lipase catalysis in organic media induced by
      purification and catalyst engineering.
AB  - A purified lipase preparation from Candida rugosa was compared to its crude
      counterpart in anhydrous and slightly hydrated hydrophobic organic solvents. The
      purified lipase preparation was less active than the crude enzyme in dry n
      heptane, whereas the presence of small concentrations of added water dramatically
      activated the purified enzyme but not the crude enzyme. Thus, in the presence of
      as little as 0.25 microL/mL of added water in n-heptane, the purified enzyme is
      over 230-fold more active and 6-fold more enantioselective than the dry enzyme
      suspension in the esterification of racemic 2-(4-chlorophenoxy)propionic acid
      with n-butanol. The reactivity and selectivity of this biocatalyst, however, was
      affected by coalescence of the enzyme preparation suspended in the wet organic
      solvent. Engineering the biocatalyst environment by dissolving the purified
      lipase in aqueous buffer and then adding this solution to n-heptane resulted in a
      precipitated enzyme preparation with smaller particle sizes that did not coalesce
      severely. In the presence of 5 microL/mL of water added with the enzyme, this
      pretreatment resulted in an activation over the dry, purified enzyme preparation
      of over 1800-fold and nearly enantiospecific catalysis (E > 100). Hence, by
      simply modifying the way enzymes are hydrated, dramatic activation of catalytic
      competency can be achieved.

PMID- 18629897
TI  - Biosynthesis of synthons in two-liquid-phase media.
AB  - The Pseudomonas oleovorans alkane hydroxylase and xylene oxygenase from
      Pseudomonas putida are versatile mono-oxygenases for stereo- and regioselective
      oxidation of aliphatic and aromatic hydrocarbons. Pseudomonas oleovorans and
      alkanol dehydrogenase deficient mutants of Pseudomonas have previously been used
      to produce alkanols from various alkanes and optically active epoxides from
      alkenes. Similarly, P. putida strains have been used to produce aromatic
      alcohols, aromatic acids, and optically active styrene oxides. A limitation in
      the use of Pseudomonas strains for bioconversions is that these strains can
      degrade some of the products formed. To counter this problem, we have constructed
      Escherichia coli recombinants, which contain the alk genes from the OCT plasmid
      of P. oleovorans [E. coli HB101 (pGEc47)] and the xylMA genes from the TOL
      plasmid of P. putida mt-2 [E. coli HB101 (pGB63)], encoding alkane hydroxylase
      and xylene oxygenase, respectively. Escherichia coli HB101 (pGEc47) was used to
      produce octanoic acid from n-octane and E. coli HB101 (pBG63) was put to use for
      the oxidation of styrene to styrene oxide in two-liquid phase biocatalysis at
      high cell densities. The alk(+) recombinant strain E. coli HB101 (pGEc47) was
      grown to 40 g/L cell dry mass in the presence of n-octane, which was converted to
      octanoic acid by the alkane oxidation system, the product accumulating in the
      aqueous phase. The xyl(+) recombinant E. coli HB101 (pBG63) was grown to a cell
      density of 26 g/L cell dry mass in the presence of around 7% (v/v) n-dodecane,
      which contained 2% (v/v) styrene. The recombinant E. coli (xyl(+)) converted
      styrene to (S)-(+)-styrene oxide at high enantiomeric excess (94% ee) and this
      compound partitioned almost exclusively into the organic phase. Using these high
      cell-density two-liquid-phase cultures, the products accumulated rapidly,
      yielding high concentrations of products (50 mM octanoic acid and 90 mM styrene
      oxide) in the respective phases.

PMID- 18629898
TI  - Enzyme engineering aspects of biocatalysis: cofactor regeneration as example.
AB  - Reaction engineering is an important tool in the case of cofactor depending
      enzyme-catalyzed reactions. It allows the establishment of conditions resulting
      in lower product specific cofactor costs as compared with product-specific enzyme
      costs. This is shown for the stereospecific reduction of carbonyl compounds
      yielding chiral amino acids and alcohols. In continuous processes, cofactor costs
      can be reduced if the cofactor can be retained within the bioreactor or recycled
      into it after separation of the product. In case of readily water-soluble
      substrates it is even possible to recycle the cofactor during a single pass
      through a continuously operated reactor more than 4000 times because normally
      very low cofactor concentrations are sufficient to saturate the enzymes involved.
      L-tert-Leucine has been produced by reductive amination with a space-time yield
      of up to 366 g L(-1) d(-1) in a single continuously operated enzyme membrane
      reactor and a two-stage cascade. Total turnover number of the cofactor NAD(+)
      increased to 4230. (S)-1-Phenyl-2-propanol was obtained by reduction of the
      corresponding ketone in an membrane reactor with integrated extraction of the
      product. A new alcohol dehydrogenase from Rhodococcus erythropolis was used. A
      space-time yield of 63 g L(-1) d(-1) and a total turnover number of 1350 have
      been reached. L-Leucine has been produced using polymer-enlarged NADH. The total
      turnover number was 80,000 at a space-time yield of 214 g L(-1) d(-1).

PMID- 18629899
TI  - Application of high hydrostatic pressure for increasing activity and stability of
      enzymes.
AB  - Elevated hydrostatic pressure has been used to increase catalytic activity and
      thermal stability of alpha-chymotrypsin (CT). For an anilide substrate,
      characterized by a negative value of the reaction activation volume (DeltaV( not
      equal)), an increase in pressure at 20 degrees C results in an exponential
      acceleration of the hydrolysis rate catalyzed by CT reaching a 6.5-fold increase
      in activity at 4700 atm (4.7 kbar). Due to a strong temperature dependence of
      DeltaV( not equal), the acceleration effect of high pressure becomes more
      pronounced at high temperatures. For example, at 50 degrees C, under a pressure
      of 3.6 kbar, CT shows activity which is more than 30 times higher than the
      activity at normal conditions (20 degrees C, 1 atm). At pressures of higher than
      3.6 kbar, the enzymatic activity is decreased due to a pressure-induced
      denaturation.Elevated hydrostatic pressure is also efficient for increasing
      stability of CT against thermal denaturation. For example, at 55 degrees C, CT is
      almost instantaneously inactivated at atmospheric pressure, whereas under a
      pressure of 1.8 kbar CT retains its anilide-hydrolyzing activity during several
      dozen minutes. Additional stabilization can be achieved in the presence of
      glycerol, which is most effective for protection of CT at an intermediate
      concentration of 40% (v/v). There has been observed an additivity in
      stabilization effects of high pressure and glycerol: thermal inactivation of
      pressure-stabilized CT can be decelerated in a supplementary manner by addition
      of 40% (v/v) glycerol. The protection effect of glycerol on the catalytic
      activity and stability of CT becomes especially pronounced when both extreme
      factors of temperature and pressure reach critical values. For example, at
      approximately 55 degrees C and 4.7 kbar, enzymatic activity of CT in the presence
      of 40% (v/v) glycerol is severalfold higher than in aqueous buffer.The results of
      this study are discussed in terms of the hypotheses which explain the action of
      external and medium effects on protein structure, such as preferential hydration
      and osmotic pressure.

PMID- 18629900
TI  - Characterization of extremely thermostable enzymatic breakers (alpha-1,6
      galactosidase and beta-1,4-mannanase) from the hyperthermophilic bacterium
      Thermotoga neapolitana 5068 for hydrolysis of guar gum.
AB  - An alpha-galactosidase and a beta-mannanase produced by the hyperthermophilic
      bacterium, Thermotoga neapolitana 5068 (TN5068), separately and together, were
      evaluated for their ability to hydrolyze guar gum in relation to viscosity
      reduction of guar-based hydraulic fracturing fluids used in oil and gas well
      stimulation. In such applications, premature guar gum hydrolysis at lower
      temperatures before the fracturing process is completed is undesirable, whereas
      thermostability and thermoactivity are advantageous. Hyperthermophilic enzymes
      presumably possess both characteristics. The purified alpha-galactosidase was
      found to have a temperature optimum of 100-105 degrees C with a half-life of 130
      minutes at 90 degrees C and 3 min at 100 degrees C, while the purified beta
      mannanase was found to have a temperature optimum of 91 degrees C and a half-life
      of 13h at this temperature and 35 min at 100 degrees C.These represent the most
      thermostable versions of these enzymes yet reported. At 25 degrees C, TN5068
      culture supernatants, containing the two enzyme activities, reduced viscosity of
      a 0.7% (wt) guar gum solution by a factor of 1.4 after a 1.5-h incubation period
      and by a factor of 2.4 after 5 h. This is in contrast to a viscosity reduction of
      100-fold after 1.5 h and 375-fold after 5 h for a commercial preparation of these
      enzymes from Aspergillus niger. In contrast, at 85 degrees C, the TN5068 enzymes
      reduced viscosity by 30-fold after 1.5 h and 100-fold after 5 h compared to a 2.5
      fold reduction after 5 h for the control. The A. niger enzymes were less
      effective at 85 degrees C (1.6-fold reduction after 1.5 h and a 4.2-fold
      reduction after 5 h), presumably due to their thermal lability at this
      temperature. Furthermore, it was determined that the purified beta-mannanase
      alone can substantially reduce viscosity of guar solutions, while the alpha
      galactosidase alone had limited viscosity reduction activity. However, the alpha
      galactosidase appeared to minimize residual particulate matter when used in
      conjunction with the beta-mannanase. This could be the result of extensive
      hydrolysis of the alpha-1,6 linkages between mannose and galactose units in guar,
      allowing more extensive hydrolysis of the mannan chain by the beta-mannanase. The
      use of thermostable enzymatic breakers from hyperthermophiles in hydraulic
      fracturing could be used to improve well stimulation and oil and gas recovery.

PMID- 18629901
TI  - The use of confocal scanning laser microscopy and other tools to characterize
      Escherichia coli in a high-cell-density synthetic biofilm.
AB  - Properties of a novel, synthetic biofilm were examined by using confocal scanning
      laser microscopy (CSLM) in combination with fluorescent probes and by
      investigating total protein content and specific beta-galactosidase activity
      during various steps of the biofilm preparation. Viable, but nongrowing
      Escherichia coli were entrapped in 10- to 80-microm-thick multilayer films, where
      a copolymer of acrylic and vinyl acetate was the immobilization matrix. Cell
      viability and distribution within the films were evaluated by developing a
      protocol to stain the bacteria with fluorescein isothiocyanate and propidium
      iodide, thereby labeling all cells green and dead cells red, respectively.
      Confocal microscopy facilitated viewing samples in the XY and XZ planes, and
      image analysis enabled counting of the cells. These experiments showed that the
      initial viability of the entrapped bacteria was 85% to 90%, cell distribution was
      uniform in the XY plane and cell number increased with increasing depth into the
      film. Specific beta-galactosidase assays developed here allowed comparison of the
      induction of lacZin suspended and immobilized cells. These experiments
      demonstrated that rehydration was an important step in biofilm preparation, and
      E. coli cast into synthetic biofilms with cell layers of at least 20 to 35 microm
      in thickness had gene induction characteristics similar to suspended cells.

PMID- 18629902
TI  - Mesalamine-induced pleuritis in a patient with ulcerative colitis.

PMID- 18629903
TI  - Redox regulation of skeletal muscle.
AB  - The potential deleterious roles of "oxidative stress" have been studied in
      skeletal muscle for over 30 years, but recent studies have identified that
      reactive oxygen species and nitric oxide generated by skeletal muscle can exert
      regulatory roles in cell signalling processes. This "redox regulation" appears to
      depend upon the reversible oxidation of cysteine residues within key proteins
      with reversible gluathionylation and formation of protein disulphides potentially
      leading to changes in the activities of proteins such as enzymes, transcription
      factors or transporters. Control of this process is dependent upon the local
      redox environment pertaining at a subcellular level. This short review provides
      examples of redox-regulated physiological processes in skeletal muscle that
      include some activation of transcription factors and changes in gene expression
      that result from contractile activity and the modulation of force generation
      during sustained contractions. There is also increasing evidence that
      dysregulation of redox-sensitive processes plays a role in the loss of muscle
      mass and function that occurs during normal ageing and in the gross muscle
      degeneration in disorders such as the muscular dystrophies.

PMID- 18629905
TI  - Kinetics of chromate reduction during naphthalene degradation in a mixed culture.
AB  - A mixed culture of Bacillus sp. K1 and Sphingomonas paucimobilis EPA 505 was
      exposed to chromate and naphthalene. Batch experiments showed that chromate was
      reduced and naphthalene was degraded by the mixed culture. Chromate reduction
      occurred initially at a high rate followed by a decrease in rate until chromate
      reduction ceased. Chromate reduction decreased in the mixed culture when a lower
      ratio of S. paucimobilis EPA 505 to Bacillus sp. K1 was utilized. A kinetic model
      incoporating a term for the cell density ratio is proposed to describe chromate
      reduction in the mixed culture under both chromate limited and electron donor
      limited conditions. The validity of the model, and its parameter values, was
      verified by experimental data generated under a variety of initial population
      compositions and a broad range of chromate concentrations. The consistent result
      of experimental data with model predictions implies that the model is useful for
      evaluating the interactions and the use of mixed culture for chromate removal.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18629906
TI  - On-line monitoring of intracellular ATP concentration in Escherichia coli
      fermentations.
AB  - A method was developed to provide a real-time measurement of intracellular
      adenosine 5'-triphosophate (ATP) concentrations in growing Escherichia coli. The
      bacteria to be monitored must first be modified by inserting the cDNA for firefly
      luciferase expressed from a constitutive promoter. Such a construct leads to
      constant specific activity of firefly luciferase during both the lag phase and
      exponential growth. When the luciferase substrate, D-luciferin, is added to the
      medium, ATP within the cells is utilized in the luciferase-catalyzed reaction
      that produces light. The light is carried from the bioreactor to a computer-based
      detector by an optical fiber. The detected per cell light emission varies during
      exponential growth. Analysis of cytoplasm extracts shows that this variance is
      related to changes in the ATP concentration, which ranges from 1 to 6 times the
      literature value for K(M). Experimental analyses demonstrated that inner filter
      effects are not a significant factor affecting the use of this system. The method
      was tested in a benchtop fermentor at cell densities above 13 g/L dry cell
      weight. A correction factor based on the accumulated light data is calculated and
      used in real time to account for consumption of luciferin from the culture broth
      by the light producing reaction. Dissolved oxygen concentrations must be kept
      above 15% of air saturation to ensure constant light output, but no detectable
      increase in oxygen demand is seen. The method does not significantly affect
      growth or production rates. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629907
TI  - Prediction of optimal biofilm thickness for membrane-attached biofilms growing in
      an extractive membrane bioreactor.
AB  - This article presents a mathematical model of membrane-attached biofilm (MAB)
      behavior in a single-tube extractive membrane bioreactor (STEMB). MABs can be
      used for treatment of wastewaters containing VOCs, treatment of saline
      wastewaters, and nitrification processes. Extractive membrane bioreactors (EMBs)
      are employed to prevent the direct contact between a toxic volatile pollutant and
      the aerated gas by allowing counterdiffusion of substrates; i.e., pollutant
      diffuses from the tube side into the biofilm, whereas oxygen diffuses from the
      shell side into the biofilm. This reduces the air stripping problems usually
      found in conventional bioreactors. In this study, the biodegradation of a toxic
      VOC (1,2-dichloroethane, DCE) present in a synthetic wastewater has been
      investigated. An unstructured model is used to describe cell growth and cell
      decay in the MAB. The model has been verified by comparing model predicted trends
      with experimental data collected over 5 to 20-day periods, and has subsequently
      been used to model steady states in biofilm behavior over longer time scales. The
      model is capable of predicting the correct trends in system variables such as
      biofilm thickness, DCE flux across the membrane, carbon dioxide evolution, and
      suspended biomass. Steady states (constant biofilm thickness and DCE flux) are
      predicted, and factors that affect these steady states, i.e., cell endogeneous
      decay rate, and biofilm attrition, are investigated. Biofilm attrition does not
      have a great influence on biofilm behavior at low values of detachment
      coefficient close to those typically reported in the literature. Steady-state
      biofilm thickness is found to be an important variable; a thin biofilm results in
      a high DCE flux across the membrane, but with the penalty of a high loss of DCE
      via air stripping. The optimal biofilm thickness at steady state can be
      determined by trading off the decrease in air stripping (desirable) and the
      decrease in DCE flux (undesirable) which occur simultaneously as the thickness
      increases. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629908
TI  - Continuous enzymatic production of xylitol with simultaneous coenzyme
      regeneration in a charged membrane reactor.
AB  - We have developed a new process for the production of xylitol from D-xylose by
      enzyme technology. An NADH-dependent xylose reductase (XR) from Candida tenuis
      catalyzes the reduction of xylose, which is coupled to enzymatic oxidations of D
      glucose or D-xylose by glucose dehydrogenase from Bacillus cereus to make
      achievable an up to 10,000-fold regeneration of NADH per cycle of discontinuous
      conversion. Using a simple kinetic model as a tool for process optimization,
      suitable conditions with regard to performance and stability of the multi
      component reaction system were established, and 300 g/L of substrate could be
      converted in yields above 96% in one single batch reaction. Due to selective and
      over 98% complete retention of the native coenzyme by negatively charged
      nanofiltration membranes used in a continuously operated enzyme reactor, a
      specific productivity of 80 g xylitol per liter, day, and kilounit of XR was
      maintained over the 150-h reaction time with only a single dosage of NADH. (c)
      1996 John Wiley & Sons, Inc.

PMID- 18629909
TI  - Cell harvesting by cross-flow microfiltration using a shear-enhanced module.
AB  - Protein, produced by a bacterial culture of recombinant Vibrio cholerae, was
      separated from cells in a fermentation broth by cross-flow microfiltration. A
      new, mechanically agitated (rotational) shear filter, the DMF(TM) filter from
      Pall, was used to perform the separation. Higher protein recovery and permeate
      flux than commonly obtained during cell harvesting were demonstrated using
      sixfold concentration followed by twofold diafiltration. The transmembrane
      pressure only increased by 10 kPa when the flux was kept constant at 150 L/m(2) h
      during both concentration and diafiltration. The protein transmission was about
      100% initially, and over 90% at the end of the concentration process. The protein
      transmission during the diafiltration was over 80%. The total recovery of protein
      was 97%. When using an enzymatic cleaning agent, no significant pure water flux
      decrease was detected during the course of the experiments. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18629910
TI  - Perturbation of syntrophic isobutyrate and butyrate degradation with formate and
      hydrogen.
AB  - The effect of formate and hydrogen on isomerization and syntrophic degradation of
      butyrate and isobutyrate was investigated using a defined methanogenic culture,
      consisting of syntrophic isobutyrate-butyrate degrader strain IB,
      Methanobacterium formicicum strain T1N, and Methanosarcina mazeii strain T18.
      Formate and hydrogen were used to perturb syntrophic butyrate and isobutyrate
      degradation by the culture. The reversible isomerization between isobutyrate and
      butyrate was inhibited by the addition of either formate or hydrogen, indicating
      that the isomerization was coupled with syntrophic butyrate degradation for the
      culture studied. Energetic analysis indicates that the direction of isomerization
      between isobutyrate and butyrate is controlled by the ratio between the two
      acids, and the most thermodynamically favorable condition for the degradation of
      butyrate or isobutyrate in conjunction with the isomerization is at almost equal
      concentrations of isobutyrate and butyrate. The degradation of isobutyrate and
      butyrate was completely inhibited in the presence of a high hydrogen partial
      pressure (>2000 Pa) or a measurable level of formate (10 muM or higher).
      Significant formate (more than 1 mM) was detected during the perturbation with
      hydrogen (17 to 40 kPa). Resumption of butyrate and isobutyrate degradation was
      related to the removal of formate. Energetic analysis supported that formate was
      another electron carrier, besides hydrogen, during syntrophic isobutyrate
      butyrate degradation by this culture. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629911
TI  - Growth and respiration of Petunia hybrida cells in chemostat cultures: A
      comparison of glucose-limited and nitrate-limited cultures.
AB  - Nitrate-limited and glucose-limited chemostat cultures of Petunia hybrida cells
      were compared at a specific biomass (+extracellular product) formation rate of
      0.0042 C.mol/C.mol h. The composition of the biomass differed considerably in
      both culture types. The N/C (mol/mol) ratio in the biomass was almost four times
      lower in the nitrate-limited than in the glucose-limited cultures. On a dry
      weight basis (g/g DW) the biomass in the nitrate-limited cultures contained about
      2.5 times less ions and protein N and about 2.5 times more carbohydrates than the
      biomass in the glucose-limited cultures. On a fresh weight basis (mmol/g FW) the
      biomass in nitrate-limited and glucose-limited cultures differed mainly in
      carbohydrate content. The yields of biomass on glucose and oxygen were generally
      higher in the nitrate-limited than in the glucose-limited cultures. Average
      values for these parameters were 0.27 C . mol biomass/C . mol glucose and 0.42 C
      . mol biomass/mol O(2) in the glucose-limited cultures and 0.34 C . mol biomass/C
      . mol glucose and 0.55 C . mol biomass/mol O(2) in the nitrate-limited cultures.
      On a C . mol basis the total respiration was about 25% and the maximally
      attainable cytochrome pathway activity (measured in the presence of hydroxamate)
      about 30% higher in the glucose-limited than in the nitrate-limited cultures. The
      maximally attainable activity of the alternative pathway (measured in the
      presence of KCN) was significantly lower in the glucose-limited cultures. On an
      organic N ( approximately protein) basis all respiratory parameters were
      significantly higher in the nitrate-limited cultures. In the presence of the
      respiratory uncoupler carbonyl cyanide p-trifluoromethoxy phenylhydrazone (FCCP)
      and excess glucose, cellular respiratory activity shows its maximal activity;
      under these conditions the total respiration increased more than 150% in the
      glucose-limited and only 30% in the nitrate-limited cultures. It is suggested
      that glucose-limited cultures are able to react more flexibly to changes in the
      environmental conditions than nitrate-limited cultures. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18629912
TI  - Enzymatic catalysis in organic solvents: Polyethylene glycol modified hydrogenase
      retains sulfhydrogenase activity in toluene.
AB  - Naturally occurring enzymes may be modified by covalently attaching hydrophobic
      groups that render the enzyme soluble and active in organic solvents, and have
      the potential to greatly expand applications of enzymatic catalysis. The
      reduction of elemental sulfur to hydrogen sulfide by a hydrogenase isolated from
      Pyrococcus furiosus has been investigated as a model system for organic
      biocatalysis. While the native hydrogenase catalyzed the reduction of sulfur to
      H(2)S in aqueous solution, no activity was observed when the aqueous solvent was
      replaced with anhydrous toluene. Hydrogenase modified with PEG p-nitrophenyl
      carbonate demonstrated its native biocatalytic ability in toluene when the
      reducing dye, benzyl viologen, was also present. Neither benzyl viologen nor PEG
      p-nitrophenyl carbonate alone demonstrated reducing capability. PEG modified
      cellulase and benzyl viologen were also incapable of reducing sulfur to H(2)S,
      indicating that the enzyme itself, and not the modification procedure, is
      responsible for the conversion in the nonpolar organic solvent. Sulfide
      production in toluene was tenfold higher than that produced in an aqueous system
      with equal enzyme activity, demonstrating the advantages of organic biocatalysis.
      Applications of bio-processing in nonaqueous media are expected to provide
      significant advances in the areas of fossil fuels, renewable feedstocks, organic
      synthesis, and environmental control technology. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629913
TI  - Two-dimensional versus three-dimensional culture systems: Effects on growth and
      productivity of BHK cells.
AB  - The influence of surface growth (two-dimensional microcarriers) and three
      dimensional growth (aggregates and macroporous supports) in agitated, suspended
      batch culture systems upon growth and productivity of BHK was compared. Cultures
      using three porous microcarriers (CultiSpher G, Cellsnow EX, and Cytocell), one
      nonporous microcarrier (Cytodex 3) and natural aggregates were performed in
      stirred tanks using two different agitation rates (60 and 100 RPM). With the
      exception of Cytocell, cell growth, viability, and productivity were similar when
      three-dimensional structures (porous microcarriers and aggregates) were used.
      Nonporous microcarriers only compared well at 60 RPM as growth ceased under
      overagitation. These results suggest that cultures less susceptible to fluid
      shear are advantageous for scale-up. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629914
TI  - New constraints between kinetic parameters explain the (Un)identifiability of
      enzymatic rate constants.
AB  - For an enzymatic reaction the rate constants in the assumed mechanism (k(1), k(
      1), etc.) sometimes can be calculated from the steady-state parameter values
      (V(max), K(m), etc.) and sometimes cannot. When identifiability problems occur,
      these are obscured by redundancy occurring among the steady-state parameters.
      This redundancy is only partly revealed by the known Haldane relations. We found
      the additional constraints between the parameters. These relations allow to
      predict in which situation rate constants are identifiable by steady-state
      kinetic methods. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629915
TI  - Imaging the propagation of viruses.
AB  - The propagation of viruses in a growing plaque has been measured using a digital
      image acquisition and analysis system. Plaques of phage T7 incubated at 37
      degrees C and illuminated against a dark field emerged as dark growing spots
      against a background of host bacteria. Images of the growth were acquired using a
      charge-coupled device (CCD) camera at 1-h intervals over 24 h. The first 10 h of
      plaque development coincided with rapid growth of the agar-immobilized
      Escherichia coli host, measured as a reduction in gray value. Following this
      period, the average radial velocity of plaque growth remained constant at 0.059
      mm/h while the standard deviation about this velocity increased. These results
      suggest the suitability of the system for spatially resolving the dynamics of
      viral evolution during plaque growth. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629916
TI  - On-line measurement of oxygen uptake in cell culture using the dynamic method.
AB  - Measurement of oxygen uptake rate is useful in assessing growth, viability, and
      metabolic activity. In cell culture, however, the oxygen demand is extremely
      small (typically 0.1-0.3 mM O(2)L-h) and is very difficult to measure accurately
      using conventional offgas analysis. In many industrial submerged cell culture
      systems, dissolved oxygen levels are controlled between preset limits by
      intermittent sparging of air or oxygen. This article describes a computational
      method for the automatic online determination of oxygen uptake from the dynamic
      dissolved oxygen probe response. Experimental measurements show that for a
      typical hybridoma culture, specific oxygen demand is 0.15 mM O(2)/10(9) cells/h.
      (c) 1996 John Wiley & Sons, Inc.

PMID- 18629919
TI  - Stereoselective bioconversions in continuously operated fixed bed reactors:
      Modeling and process optimization.
AB  - The nonaqueous lipase-catalyzed kinetic resolution of racemic 2-methyl-1-pentanol
      in a continuously operated fixed bed reactor was theoretically and experimentally
      studied. A 2-dimensional mathematical model was developed to predict the
      performance of the heterogeneous enantioselective biotransformation and to
      optimize the productivity and effective stereoselectivity of the process by
      taking pore diffusion, solid(SINGLEBOND)liquid mass transfer, convection, and
      axial dispersion into account. Experimental investigations were conducted with
      lipase from Pseudomonas sp. immobilized by ionic binding in the pores of the
      anion exchange resin Duolite A 568. As determined in prior initial rate
      experiments, the specific activities of the immobilized lipase were maximal at a
      water activity of approximately a(w) = 0.67 and revealed a significant dependence
      on the amount of enzyme bound to the carrier material, with enantiomeric ratios
      slightly increasing with increasing water activities. Continuous resolution
      processes were carried out at a wide range of enzyme loadings. By controlled
      immobilization according to the theoretically evaluated optimal enzyme loading,
      the continuous racemic resolution could be optimized to obtain (R)-2-methyl-1
      pentanol at high productivity and enantiopurity (ee > 95%). The steady-state
      characteristics of the system could be generally predicted by the model, despite
      the necessity to reevaluate the kinetic properties of the immobilized lipase to
      account for the complex non-aqueous microkinetics in a heterogeneous environment.
      Further model extension introducing competitive inhibition of free water in
      solutions as well as water diffusion and adsorption to the biocatalyst were
      useful in providing a more accurate description of the experimental results. (c)
      1996 John Wiley & Sons, Inc.

PMID- 18629917
TI  - Chromium supplementation improves glucose tolerance in diabetic Goto-Kakizaki
      rats.
AB  - Chromium supplementation (Cr) may be useful in the management of diabetes and
      appears to improve some aspects of glucose handling. However, several studies
      have used either high doses of Cr supplementation or have placed control animals
      on a Cr-deficient diet. We therefore wanted to test whether Cr dosages in the
      ranges that more closely approximate recommended levels of supplementation in
      humans are efficacious in glycemic control under normal dietary conditions.
      Euglycemic Wistar or diabetic Goto-Kakizaki (GK) rats (a model of nonobese NIDDM)
      were assigned to water (control) or chromium picolinate (Cr-P) supplementation (1
      or 10 mg/kg/day) groups for up to 32 weeks. Glucose tolerance was tested
      following an overnight fast by injecting sterile glucose (1.0 g/kg, i.p.) and
      then measuring blood glucose at select times to determine the sensitivity to
      glucose by calculation of the area under the curve. Cr-P did not significantly
      alter the growth of the animals. In the euglycemic Wistar rats, Cr-P
      supplementation did not alter the response to a glucose tolerance test. In the GK
      rats, Cr-P supplementation significantly improved glucose tolerance at both
      levels of Cr-P supplementation (1 mg/kg/day: H20; 100 +/- 11%; Cr-P 70 +/- 8%; 10
      mg/kg/day: H(2)0; 100 +/- 10%; Cr-P 66 +/- 9 %). Cr-P supplementation produced a
      small improvement in some indices of glycemic control. There were no differences
      observed for the two levels of Cr-P supplementation suggested that we did not
      identify a threshold for Cr-P effects, and future studies may use lower doses to
      find a threshold effect for improving glucose tolerance in diabetics.

PMID- 18629920
TI  - Permeability of alginate microcapsules to secretory recombinant gene products.
AB  - Non-autologous somatic gene therapy is an alternate approach to delivering
      recombinant gene products through implantation of a "universal" donor cell line
      engineered to produce a therapeutic gene product. The cells are immunologically
      isolated by enclosure in immunoprotective microcapsules fabricated from alginate
      poly-L-lysine-alginate. The molecular weight cutoff of these microcapsules was
      thought to be <100 kd, thus, excluding the immunoglobulins. However, when such
      microcapsules are fabricated to enclose cells, they show a higher permeability
      threshold than expected. The secretion rates of recombinant gene products ranging
      from 21 through 150 to 300 kd (human growth hormone, rat serum albumin, human
      arylsulfatase A, human immunoglobulin, mouse beta-hexosaminidase, mouse beta
      glucuronidase) were similar between the nonencapsulated and encapsulated
      recombinant cells with the exception of the largest molecular species, the 300-kd
      beta-glucuronidase. Its secretion was reduced about eightfold after
      encapsulation. Increasing the thickness of the membrane by prolonging the coating
      time with poly-L-lysine did not provide a lower molecular weight cutoff. An
      additional coating with alginate, however, reduced the leakage of the larger
      molecular species, but the effect was short lived: After 2 weeks in culture, the
      double- and single-coated microcapsules were equally permeable. Both the
      increased poly-L-lysine and alginate coating were detrimental to the long-term
      viability and proliferation of the encapsulated cells. Hence, immunoisolation of
      encapsulated cells with alginate-poly-L-lysine-alginate microcapsules cannot
      provide a molecular weight cutoff below 300 kd. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629921
TI  - Optimization of regulatory architectures in metabolic reaction networks.
AB  - Successful biotechnological applications, such as amino acid production, have
      demonstrated significant improvement in bioprocess performance by genetic
      modifications of metabolic control architectures and enzyme expression levels.
      However, the stoichiometric complexity of metabolic pathways, along with their
      strongly nonlinear nature and regulatory coupling, necessitates the use of
      structured kinetic models to direct experimental applications and aid in
      quantitative understanding of cellular bioprocesses. A novel optimization problem
      is introduced here, the objective of which is to identify changes in the
      regulatory characteristics of pertinent enzymes and in their cellular content
      which should be implemented to optimize a particular metabolic process. The
      mathematical representation of the metabolic reaction networks used is the S
      system representation, which at steady state is characterized by linear
      equations. Exploiting the linearity of the representation, we formulated the
      optimization problem as a mixed-integer linear programming (MILP) problem. This
      formulation allows the consideration of a regulatory superstructure that contains
      all alternative regulatory structures that can be considered for a given pathway.
      The proposed approach is developed and illustrated using a simple linear pathway.
      Application of the framework on a complicated pathway-namely, the xanthine
      monophosphate (XMP) and guanosine monophosphate (GMP) synthesis pathway
      identified the modification of the regulatory architecture that, along with
      changes in enzyme expression levels, can increase the XMP and GMP concentration
      by over 114 times the reference value, which is 50 times more than could be
      achieved by changes in enzyme expression levels only. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18629922
TI  - Separation of hemoglobin and myoglobin from yellowfin tuna red muscle by
      ultrafiltration: Effect of pH and ionic strength.
AB  - Efficiency and selectivity of 30 and 150 kd inorganic ultrafiltration membranes
      (Techsep) toward tuna hemoglobin and myoglobin were studied. The influence of pH
      and ionic strength was investigated. Mass flow of myoglobin was higher at its
      isoelectric pH (8.6) and for low ionic strength (1.5 mM). This result was related
      to the absence of electrostatic repulsion between myoglobin and the surface of
      the dynamic membrane. The use of high ionic strength 0.15 M NaCl involved an
      apparent dimerisation of myoglobin and consequently a lower permeation through
      the membrane due to the molecular weight increase. The permeation and retention
      of hemoglobin did not agree with the effect of pH observed with myoglobin (best
      permeation at isoelectric pH) but followed the behavior of myoglobin. This was
      explained by a myoglobin concentration 10 times higher than hemoglobin
      concentration. The yield of retention selectivity was investigated. Selectivity
      of the membrane at pH 8.6 and 1.5 mM was favorable to myoglobin (increase of 40%)
      whereas a reversed selectivity was observed at pH 7.3, 0.15 M. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18629923
TI  - Polysaccharide concentration and molecular weight effects on the oxygen mass
      transfer in a reciprocating plate bioreactor.
AB  - In most polysaccharide fermentations, the nature of the fermentation broth
      changes drastically with time and, as a result, the overall oxygen mass transfer
      coefficient (K(L)a) can vary by orders of magnitude. To obtain a better
      understanding of this phenomenon, an experimental program was devised to study
      the respective influence of molecular weight and concentration of dextran
      solutions on K(L)a. Experiments were conducted in a reciprocating plate
      bioreactor. This bioreactor uses a stack of perforated plates that is
      reciprocated axially in the column and it is therefore well suited for mixing
      viscous liquid broths and providing uniform overall mass transfer coefficients.
      The variation of K(L)a with the power input per unit volume and the superficial
      gas velocity were obtained for three ranges of molecular weights and five
      concentrations of dextran. In every medium, two regimes of operation were
      observed as a function of the power input per unit volume: a first regime, at low
      power inputs per unit volume where K(L)a remains constant until a threshold of
      power input is attained; and a second regime, which is characterized by a steep
      increase of K(L)a as a function of the power input per unit volume. The presence
      of dissolved biological macromolecules, not only because of their effect on the
      rheology of the medium but also because their effect on the gas-liquid interface,
      has a significant impact on K(L)a. It was found that, generally, small
      concentrations of polysaccharide favor oxygen mass transfer despite the increase
      in medium viscosity. However, the respective influence of polysaccharide
      concentration and molecular weight was different for the two regimes of
      operation. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629924
TI  - CHO DUKX cell lineages preadapted to growth in serum-free suspension culture
      enable rapid development of cell culture processes for the manufacture of
      recombinant proteins.
AB  - Using an adaptive strategy, Chinese hamster ovary (CHO) cell lines were developed
      that are capable of robust growth in serum-free suspension culture. These
      preadapted derivatives of the commonly used strain of CHO cells (CHO DUKX),
      termed PA-DUKX, were used for the introduction and stable expression of several
      heterologous human genes. A significant advantage of recombinant PA-DUKX cells
      was their ability to readily resume growth in serum-free suspension culture after
      transfection and amplification of heterologous genes. Expression of recombinant
      human proteins in PA-DUKX cells was quantitatively similar to that of lineages
      generated using conventional CHO DUKX cells. In addition, recombinant human
      proteins expressed by transfected PA-DUKX lineages were shown to be biochemically
      and structurally similar to those expressed in CHO DUKX cells, PA-DUKX host cell
      technology provides an opportunity for reducing the time and resources required
      to develop large-scale, suspension culture-based manufacturing processes
      employing serum-free medium. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629925
TI  - Determinants of liposome partitioning in aqueous two-phase systems: Evaluation by
      means of a factorial design.
AB  - This article evaluates the influence of five parameters on liposome partitioning
      in aqueous two-phase systems (ATPSs), composed of poly(ethyleneglycol)
      (PEG)/dextran (Dx), using the factorial experimental design together with a
      multiple regression. Mathematical models to quantify the influence of these
      parameters, individually and/or jointly, on liposome partitioning in ATPS were
      developed. The models were statistically tested and verified by experimentation.
      This approach was then used to define the conditions for the preferential
      accumulation of liposomes in the top PEG-rich phase. The models predicted a
      significant effect of liposome surface charge, PEG molecular weight, phase
      forming polymer concentration, and phosphate ion concentration on the partition
      behavior of liposomes. For negatively charged liposomes, it was found that the
      smaller the molecular weight of PEG and polymer concentration and the larger the
      phosphate ion concentration, the greater the partition coefficient of the
      liposomes. No significant effect of pH, at the range of 6-8, on liposome
      partitioning was noted. This approach has led to the development of an optimal
      two-phase system where 90% of negatively charged liposomes accumulated in the PEG
      phase. In addition to the general scientific value of this research, it has a
      technological importance as ATPSs may be useful for removing the unentrapped drug
      from liposomes during their preparation for pharmaceutical applications. (c) 1996
      John Wiley & Sons, Inc.

PMID- 18629927
TI  - Selective extraction using preferential transport through adsorptive membranes.
AB  - Selective extraction of a protein from a mixture can be accomplished using an
      adsorptive membrane and low displacement recuperative parametric pumping. Low
      displacement recuperative parametric pumping can lead to the preferential
      transport of an adsorbing solute and the rejection of nonadsorbing solutes by the
      adsorptive membrane. Using a protein mixture consisting of lysozyme and
      myoglobin, we have found the conditions under which lysozyme is preferentially
      transported through an ion-exchange membrane cartridge while myoglobin is
      rejected by the membrane. Trends observed when parameters such as the desorbent
      concentration, feed concentration, and flow rate are varied agree with the
      predictions of a mathematical model. Comparison with facilitated diffusion shows
      that preferential transport can lead to higher solute fluxes, albeit at lower
      selectivity. Additionally, preferential transport can be used to transport a
      solute up a concentration gradient and to selectively extract a solute from a
      feed that contains suspended solids.

PMID- 18629928
TI  - Kinetic, dynamic, and pathway studies of glycerol metabolism by Klebsiella
      pneumoniae in anaerobic continuous culture: I. The phenomena and characterization
      of oscillation and hysteresis.
AB  - Oscillation and hysteresis phenomena are observed in the anaerobic continuous
      fermentation of glycerol by Klebsiella pneumoniae in long-term cultivations under
      a variety of conditions. In this work, the conditions for the occurrence of these
      phenomena are reported and the patterns of cell growth and metabolism under
      oscillation are characterized. During an oscillation period, the formation rates
      of CO(2), H(2), and formate and the consumption rate of alkali periodically pass
      values of maxima and minima, the latter being close to zero. The formation of
      biomass and fermentation products such as 1,3-propanediol, acetate, and ethanol
      also undergo periodic changes which shift maxima and minima. Sustained
      oscillation occurs only under conditions of substrate excess within a distinct
      regime. At pH 7.0, it is only found at dilution rates above 0.15 h(-1) under the
      experimental conditions. At lower pH values, oscillations are more likely to
      happen, even at a relatively low dilution rate and low substrate excess. Whereas
      the amplitude of oscillations at pH 7.0 depends on both the dilution rate and the
      residual glycerol concentration (C(Glyc)) the interval of oscillations appears to
      be only a function of C(Glyc). An increase of C(Glyc) in culture damps the
      oscillation and leads to its disappearance at C(Glyc) = 1100 to 1200 mmol/L (pH
      7.0). The operation mode was also found to be an important parameter in
      determining the stability and actual state of the culture, resulting in
      hysteresis under certain conditions, particularly at low pH values. Generally, a
      large perturbation of cultivation conditions tends to cause oscillation and
      hysteresis. The results unambiguously demonstrate that the oscillation and
      hysteresis phenomena shown in this work are bound to genuine metabolic
      fluctuations of the microorganism. They reveal several differences and new
      features compared with those reported in the literature and cannot be readily
      explained by the mechanisms known so far.

PMID- 18629929
TI  - Kinetic, dynamic, and pathway studies of glycerol metabolism by Klebsiella
      pneumoniae in anaerobic continuous culture: II. Analysis of metabolic rates and
      pathways under oscillation and steady-state conditions.
AB  - The oscillation phenomena reported in the preceding article for the anaerobic
      continuous fermentation of glycerol by Klebsiella pneumoniae are analyzed in
      terms of metabolic fluxes (metabolic rates and yields) and stoichiometry of
      pathways. Significant oscillations in the fluxes of CO(2), H(2), formic acid,
      ethanol, and reducing equivalents are observed which show obvious relationships
      to each other. Changes in the consumption or production rates of glycerol, acetic
      acid, 1,3-propanediol, and ATP are irregular and have relatively small amplitudes
      compared with their absolute values. By comparing the metabolic fluxes under
      oscillation and steady state that have nearly the same environmental conditions
      it could be shown that pyruvate metabolism is the main step affected under
      oscillation conditions. The specific formation rates of all the products
      originating from pyruvate metabolism (CO(2), H(2), formic acid, ethanol, acetic
      acid, lactic acid, and 2,3-butanediol) show significant differences under
      conditions of oscillation and steady state. In contrast, the specific rates of
      substrate uptake, ATP generation, and formation of products deriving either
      directly from glycerol (1,3-propanediol) or from the upstream of pyruvate
      metabolism (e.g., succinic acid) are not, or at least not significantly, affected
      during oscillation. Stoichiometric analysis of metabolic pathways confirms that
      other enzyme systems, in addition to pyruvate: formate-lyase, must be
      simultaneously involved in the pyruvate decarboxylation under both oscillation
      and steady-state conditions. The results strongly suggest oscillations of
      activities of these enzymes under oscillation conditions. It appears that the
      reason for the occurrence of oscillation and hysteresis lies in an unstable
      regulation of pyruvate metabolism of different enzymes triggered by substrate
      excess and drastic change(s) of environmental conditions.

PMID- 18629930
TI  - Characterization of an oxygen-dependent inducible promoter system, the nar
      promoter, and Escherichia coli with an inactivated nar operon.
AB  - The nar promoter of Escherichia coli, which is maximally induced under anaerobic
      conditions in the presence of nitrate, was characterized to see whether the nar
      promoter cloned onto pBR322 can be used as an inducible promoter. To increase the
      expression level, the nar promoter was expressed in E. coli where active nitrate
      reductase cannot be expressed from the nar operon on the chromosome. A plasmid
      with the lacZ gene expressing beta-galactosidase instead of the structural genes
      of the nar operon was used to simplify an assay of induction of the nar promoter.
      The following effects were investigated to find optimal conditions: methods of
      inducing the nar promoter, optimal nitrate and molybdate concentrations maximally
      inducing the nar promoter, the amount of expressed beta-galactosidase, and
      induction ratio (specific beta-galactosidase activity after maximal
      induction/specific beta-galactosidase activity before induction). The following
      results were obtained from the experiments: induction of the nar promoter was
      optimal when E. coli was grown in the presence of 1% nitrate at the beginning of
      culture; expression of beta-galactosidase was not affected by molybdate; the
      induction ratio was maximal, approximately 300, when the overnight culture was
      grown in the flask for 2.5 h (OD(600) is congruent to 1.3) before being
      transferred to the fermentor; the amount of beta-galactosidase per cell and per
      medium volume was maximal when E. coli was grown under aerobic conditions to
      OD(600) = 1.7; then the nar promoter was induced under microaerobic conditions
      made by lowering dissolved oxygen level (DO) to 1-2%. After approximately 6 h of
      induction, OD(600) became 3.2 and specific beta-galactosidase activity became
      36,000 Miller units, equivalent to 35% of total cellular proteins, which was
      confirmed from sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

PMID- 18629931
TI  - Material balance studies on animal cell metabolism using a stoichiometrically
      based reaction network.
AB  - A detailed reaction network of mammalian cell metabolism contains hundreds of
      enzymatic reactions. By grouping serial reactions into single overall reactions
      and separating overlapped pathways into independent reactions, the total number
      of reactions of the network is significantly reduced. This strategy of
      manipulating the reaction network avoids the manipulations of a large number of
      reactions otherwise needed to determine the reaction extents. A stoichiometric
      material balance model is developed based on the stoichiometry of the simplified
      reaction network. Closures of material balances on glucose and each of the 20
      amino acids are achieved using experimental data from three controlled fed-batch
      and one-batch hybridoma cultures. Results show that the critical role of
      essential amino acids, except glutamine, is to provide precursors for protein
      synthesis. The catabolism of some of the essential amino acids, particularly
      isoleucine and leucine, is observed when an excess amount of these amino acids is
      available in the culture medium. It was found that the reduction of glutamine
      utilization (for reducing ammonia production) is accompanied by an increase in
      the uptake of nonessential amino acids (NAAs) from the culture medium. This
      suggests that NAAs are necessary even though they are not essential for cell
      growth. A glutamine balance shows that less than 20% of the glutamine nitrogen is
      utilized for essential roles, such as protein and nucleotide syntheses. A
      relatively constant percentage (about 45%) of the glutamine nitrogen is utilized
      for NAA biosynthesis, despite the fact that the absolute amount varies among the
      four experiments. As to the carbon skeleton of glutamine, a significant portion
      enters the tricarboxylic acid (TCA) cycle. A material balance on glucose shows
      that most of the glucose (81%) is converted into lactate when glucose is in
      excess. On the other hand, when glucose is limited, lactate production is
      considerably reduced, while a major portion of glucose (48%) enters the TCA
      cycle. The fraction of glucose used for the synthesis of cellular components
      ranges from 9 to 28%.

PMID- 18629932
TI  - Energy metabolism and ATP balance in animal cell cultivation using a
      stoichiometrically based reaction network.
AB  - A metabolic reaction network is developed for the estimation of the
      stoichiometric production of adenosine triphosphate (ATP) in animal cell culture.
      By using the material balance data from fed-batch and batch cultures of hybridoma
      cells, the stoichiometric ATP productions are determined with estimated effective
      P/O ratios of 2 for NADH and 1.2 for FADH(2). A significant percentage of the ATP
      requirement (16-41%) in hybridoma cells is generated directly from free energy
      release without the participation of oxygen. The oxidative phosphorylation of
      NADH accounts for about 60% of the total ATP production in the fed-batch cultures
      and about 47% in the batch culture. The oxidative phosphorylation of FADH(2)
      accounts for less then 20% of the total ATP production in all cases.A fractional
      model is devised to analyze the contribution of each nutrient to the ATP
      production. Results show that a majority of the ATP is produced from glucose
      metabolism (60-76%). Less than 30% of the ATP is derived from glutamine, and less
      than 11% is derived from other essential amino acids. The analysis also shows
      that the glycolytic pathway generates more ATP in the batch (41%) than in the fed
      batch (<27%) cultures. The TCA cycle provides 51-68% of the total ATP production.
      The calculated stoichiometric oxygen consumption differs among the batch and fed
      batch cultures, depending on the glucose concentration. This result suggests that
      the relationship between the oxygen uptake rate (OUR) and cell growth may change
      with the culture conditions. However, the calculated respiratory quotient (RQ) is
      relatively constant in all cases.A linear relationship is obtained between the
      specific ATP production rate and the specific cell growth rate. The maximum ATP
      yield and the maintenance ATP requirement are determined based on this linear
      relationship. The biosynthetic ATP demand estimated from the dry cell weight and
      cell composition is significantly lower than that calculated from the maximum ATP
      yield, indicating that the non-growth-associated ATP demand may contain other
      factors than what is considered in the estimation of the biosynthetic ATP demand.

PMID- 18629933
TI  - Modeling substrate inhibition of microbial growth.
AB  - This article presents a general equation for substrate inhibition of microbial
      growth using a statistical thermodynamic approach. Existing empirical models
      adapted from enzyme kinetics, for example, the Haldane-Andrews equation, often
      criticized for not being physically based for microbial growth, are shown to
      derive from the general equation in this article, and their empirical parameters
      are shown to be well defined physically. Three sets of experimental data from the
      literature are used to test the modeling abilities of the general equation to
      represent experimental data. The results are compared with those obtained by
      fitting the same data set to a widely used empirical model existing in the
      literature. The general equation is found to represent all three experimental
      data sets better than the alternative model tested. In addition, a graphical
      method existing in enzyme kinetics is successfully adapted and further developed
      to determine the number of inhibition sites of a basic functional unit of a
      bacterial cell.

PMID- 18629934
TI  - Structural basis for the molecular memory of imprinted proteins in anhydrous
      media.
AB  - Fourier-transform infrared (FTIR) spectroscopy has been used to quantitatively
      examine the secondary structure of imprinted (i.e., lyophilized in the presence
      of multifunctional ligands followed by removal of the latter) proteins in
      anhydrous media. Lysozyme, chymotrypsinogen, and bovine serum albumin, imprinted
      with L-malic acid, all exhibited significant differences in the secondary
      structure compared to that of their nonimprinted counterparts. A rise in the beta
      sheet content, which invariably occurs upon lyophilization, is substantially
      lower for imprinted proteins. Alterations in the alpha-helix contents of these
      proteins have also been observed upon imprinting, although these changes are
      specific to the protein. A structural explanation has been obtained herein for
      other previously observed aspects of the protein imprinting phenomenon, including
      the effects of the ligand and the solvent and the lack of enantioselectivity.
      Exposure to aqueous solution, but not to anhydrous solvents, results in the
      disappearance of imprinting-induced changes in the secondary structure of
      proteins.

PMID- 18629935
TI  - Regulation of ribosome synthesis in Escherichia coli: effects of temperature and
      dilution rate changes.
AB  - The effect of temperature on the synthesis of ribosome in Escherichia coli K-12
      was investigated. In continuous fermentation, the total and functioning ribosome
      contents decreased with increasing temperature, while the non-functioning
      ribosome content remained unchanged. Cells contained higher amounts of
      functioning ribosome at lower temperatures to compensate for the decrease in
      translational activity. A transient study was performed to investigate the
      dynamic response of the cell to changes in the dilution rate. In response to the
      dilution rate shift-up, the cell mass decreased until the cells produced a
      sufficient amount of ribosomes to support the new higher growth rate. However,
      the response to the dilution rate shift-down resulted in an immediate increase in
      cell mass. This may be due to the fact that the cell already contains enough
      ribosomes to support a lower growth rate corresponding to the new low dilution
      rate. Based on the experimental results, a mathematical model was developed to
      describe the cell growth at transient as well as steady states. The total
      ribosome content was included as a variable because it affects the growth rate of
      the cell.

PMID- 18629936
TI  - Fixation and stabilization of Escherichia coli cells displaying genetically
      engineered cell surface proteins.
AB  - A large biotechnological potential is inherent in the display of proteins (e.g.,
      enzymes, single-chain antibodies, on the surface of bacterial cells) (Georgiou et
      al., 1993). Applications such as immobilized whole-cell biocatalysts or cellular
      adsorbents require cell fixation to prevent disintegration, stabilization of the
      anchored protein from leakage, denaturation or proteolysis, and total loss of
      cell viability, preventing medium and potential product contamination with cells.
      In this article we describe the adaptation of a simple two-stage chemical
      crosslinking procedure based on "bi-layer encagement" (Tor et al., 1989) for
      stabilizing Escherichia coli cells expressing an Lpp-OmpA (46-159)-beta-lactamase
      fusion that displays beta-lactamase on the cell surface. Bilayer crosslinking and
      coating the bacteria with a polymeric matrix is accomplished by treating the
      cells first with either glutaraldehyde or polyglutaraldehyde, followed by
      secondary crosslinking with polyacrylamide hydrazide. These treatments resulted
      in a 5- to 25-fold reduction of the thermal inactivation rate constant at 55
      degrees C of surface anchored beta-lactamase and completely prevented the
      deterioration of the cells for at least a week of storage at 4 degrees C. The
      stabilization procedure developed paves the way to scalable biotechnological
      applications of E. coli displaying surface anchored proteins as whole-cell
      biocatalysts and adsorbents.

PMID- 18629937
TI  - Pathway kinetics and metabolic control analysis of a high-yielding strain of
      Penicillium chrysogenum during fed batch cultivations.

PMID- 18629938
TI  - SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that
      evolved from its inhibitory counterpart SIGLEC11 and has functional and non
      functional alleles in humans.
AB  - Sialic acid binding immunoglobulin-like lectins (Siglec) are important components
      of immune recognition. The organization of Siglec genes in different species is
      consistent with rapid selection imposed by pathogens. We studied SIGLEC11 genes
      in human, rodent, dog, cow and non-human primates. The lineages of SIGLEC11 genes
      in these species have undergone dynamic gene duplication and conversion, forming
      a potential inhibitory (SIGLEC11)/activating (SIGLEC16) receptor pair in
      chimpanzee and humans. A cDNA encoding human Siglec-16, currently classed as a
      pseudogene in the databases (SIGLECP16), is expressed in various cell lines and
      tissues. A polymorphism screen for the two alleles (wild type and four-base pair
      deletion, 4bpDelta) of SIGLEC16 found their frequencies to be 50% amongst the UK
      population. A search for donor sequences for SIGLEC16 revealed a subfamily of
      activating Siglec with charged transmembrane domains predicted to associate with
      ITAM-encoding adaptor proteins. In support of this, Siglec-16 was expressed at
      the cell surface in the presence of DAP12, but not the FcRgamma chain. Using
      antisera specific to the cytoplasmic tail of Siglec-16, we identified Siglec-16
      expression in CD14(+) tissue macrophages and in normal human brain, cancerous
      oesophagus and lung. This is the first activating human Siglec receptor found to
      have functional and non-functional alleles within the population.

PMID- 18629939
TI  - Distinct molecular composition of blood and lymphatic vascular endothelial cell
      junctions establishes specific functional barriers within the peripheral lymph
      node.
AB  - Lymph nodes are strategically localized at the interfaces between the blood and
      lymphatic vascular system, delivering immune cells and antigens to the lymph
      node. As cellular junctions of endothelial cells actively regulate vascular
      permeability and cell traffic, we have investigated their molecular composition
      by performing an extensive immunofluorescence study for adherens and tight
      junction molecules, including vascular endothelium (VE)-cadherin, the vascular
      claudins 1, 3, 5 and 12, occludin, members of the junctional adhesion molecule
      family plus endothelial cell-selective adhesion molecule (ESAM)-1, platelet
      endothelial cell adhesion molecule-1, ZO-1 and ZO-2. We found that junctions of
      high endothelial venules (HEV), which serve as entry site for naive lymphocytes,
      are unique due to their lack of the endothelial cell-specific claudin-5. LYVE
      1(+) sinus-lining endothelial cells form a diffusion barrier for soluble
      molecules that arrive at the afferent lymph and use claudin-5 and ESAM-1 to
      establish characteristic tight junctions. Analysis of the spatial relationship
      between the different vascular compartments revealed that HEV extend beyond the
      paracortex into the medullary sinuses, where they are protected from direct
      contact with the lymph by sinus-lining endothelial cells. The specific molecular
      architecture of cellular junctions present in blood and lymphatic vessel
      endothelium in peripheral lymph nodes establishes distinct barriers controlling
      the distribution of antigens and immune cells within this tissue.

PMID- 18629940
TI  - Site-directed mutagenesis of the chemokine receptor CXCR6 suggests a novel
      paradigm for interactions with the ligand CXCL16.
AB  - Chemokine receptor CXCR6 mediates the chemotaxis and adhesion of leukocytes to
      soluble and membrane-anchored forms of CXCL16, and is an HIV-1 co-receptor. Here,
      we describe the effects of mutation of acidic extracellular CXCR6 residues on
      receptor function. Although most CXCR6 mutants examined were expressed at levels
      similar to wild-type (WT) CXCR6, an N-terminal E3Q mutant was poorly expressed,
      which may explain previously reported protective effects of a similar single
      nucleotide polymorphism, with respect to late-stage HIV-1 infection. In contrast
      to several other chemokine receptors, mutation of the CXCR6 N terminus and
      inhibition of post-translational modifications of this region were without effect
      on receptor function. Likewise, N-terminal extension of CXCL16 resulted in a
      protein with decent potency and efficacy in chemotaxis and not, as anticipated, a
      CXCR6 antagonist. D176N and E274Q CXCR6 mutants were unable to interact with
      soluble CXCL16, suggesting a critical role for D176 and E274 in ligand binding.
      Intriguingly, although unable to interact with soluble CXCL16, the E274Q mutant
      could promote robust adhesion to membrane-anchored CXCL16, suggesting that
      soluble and membrane-bound forms of CXCL16 possess distinct conformations.
      Collectively, our data suggest a novel paradigm for the CXCR6:CXCL16 interaction,
      a finding which may impact the discovery of small-molecule antagonists of CXCR6.

PMID- 18629942
TI  - A Monte Carlo simulation of plasmid replication during the bacterial division
      cycle.
AB  - Plasmids have cell cycle replication patterns that need to be considered in
      models of their replication dynamics. To compare current theories for control of
      plasmid replication with experimental data for timing of plasmid replication with
      the cell cycle, a Monte Carlo simulation of plasmid replication and partition was
      developed. High-copy plasmid replication was simulated by incorporating equations
      previously developed from the known molecular biology of ColE1-type plasmids into
      the cell-cycle simulation. Two types of molecular mechanisms for low-copy plasmid
      replication were tested: accumulation of an initiator protein in proportion to
      cell mass and binding of the plasmid origin to the cell membrane. The low-copy
      plasmids were partitioned actively, with a specific mechanism to mediate the
      transfer from mother to daughter cells, whereas the high-copy plasmids were
      partitioned passively with cell mass.The simulation results and experimental data
      demonstrate cell-cycle-specific replication for the low-copy F plasmid and cell
      cycle-independent replication for the high-copy pBR322, ColBM, and R6K plasmids.
      The simulation results indicate that synchronous replication at multiple plasmid
      origins is critical for the cell-cycle-specific pattern observed in rapidly
      growing cells. Variability in the synchrony of initiation of multiple plasmid
      origins give rise to a cell-cycle-independent pattern and is offered as a
      plausible explanation for the controversy surrounding the replication pattern of
      the low-copy plasmids. A comparison of experimental data and simulation results
      for the low-copy F plasmid at several growth rates indicates that either
      initiation mechanism would be sufficient to explain the timing of replication
      with the cell cycle. The simulation results also demonstrate that, although cell
      cycle-specific and cell-cycle independent replication patterns give rise to very
      different gene-expression patterns during short induction periods in age-selected
      populations, long-term expression of genes encoded on low-copy and high-copy
      plasmids in exponentially growing cells have nearly the same patterns. These
      results may be important for the future use of low-copy plasmids as expression
      vectors and validate the use of simpler models for high-copy plasmids that do not
      consider cell-cycle phenomena. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629943
TI  - Preparation of 3-deacetyl cephalosporins by Aspergillus niger lipase.
AB  - Lipase from Aspergillus niger was used for the selective hydrolysis of the 3-O
      acetate of cephalosporin C to give an intermediate useful for further chemical
      elaborations. This lipase was purified to homogeneity and its properties compared
      with previously published data that present some discrepancies. The lipase proved
      to be very effective in catalyzing 3-O-acetate hydrolysis and versatile toward
      substitution on the beta-lactamic ring. In fact, as an example, two other
      cephalosporinic derivatives, cephalotin and cefotaxime, were efficiently
      deacetylated. The lipase was immobilized on Eupergit C and employed continuously
      in either a column or a batch reactor for 2 months without appreciable loss of
      activity. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629944
TI  - Control of L-phenylalanine production by dual feeding of glucose and L-tyrosine.
AB  - Control of L-phenylalanine production by a recombinant of Escherichia coli AT2471
      by means of the dual feeding of glucose and L-tyrosine was investigated. A novel
      method was developed for on-line monitoring of the maximum glucose uptake rate
      (MGUR), in which the length of time required for the consumption of added glucose
      was measured. Accumulation of acetic acid was successfully prevented throughout
      the whole period of the culture when the glucose concentration was kept below 0.1
      g/L by controlling the glucose feeding on the basis of on-line monitoring of the
      MGUR and the cell concentration with a laser sensor.In a batch culture with
      glucose feeding, after L-tyrosine was depleted cell growth and the L
      phenylalanine production rate decreased along with decreases in the specific
      enzyme activities of chorismate mutase-p-prephenate dehydratase (CMP) and 3-deoxy
      D-arabinoheputulosonate 7-phosphate synthase (DAHP), which are the key enzymes in
      the L-phenylalanine synthesis pathway. Increasing the L-tyrosine feed rate by an
      appropriate amount, but not so far as to cause L-tyrosine accumulation in the
      culture, increased the activities of the enzymes and the specific rates of growth
      and production while the product yield based on glucose consumption decreased.The
      average specific rates of growth, production, and MGUR could be expressed as
      functions of the specific L-tyrosine consumption rate during both the earlier and
      later periods of L-tyrosine feeding. Estimations of the amount of L-phenylalanine
      produced, the product yield, and the cost factor by using these functions with
      several different combinations of two specific L-tyrosine consumption rates for
      two 10-h periods resulted in a suggested optimum L-tyrosine feeding strategy
      giving a lower specific L-tyrosine consumption rate in the later period, to
      suppress cell growth, in comparison to that in the earlier period. During L
      tyrosine feeding, the three specific rates (growth, production, and MGUR) could
      be successfully controlled by adjusting the specific L-tyrosine consumption rate
      to the predicted value. The cost factor was lowest in this controlled culture,
      demonstrating experimentally the effectiveness of the strategy. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18629945
TI  - A Fourier-transform infrared spectroscopic analysis of organic matter degradation
      in a bench-scale solid substrate fermentation (composting) system.
AB  - The degradation of organic matter was evaluated by a quantitative Fourier
      transform infrared spectroscopy (FTIR) analysis technique. The degradation
      process was conducted in a bench-scale reactor under controlled operational
      conditions of 50 degrees C, with 50-60% moisture content, and subjected to
      uniform aeration for 325 h. During the composting process, ATP concentration
      increased from 0.1 to 8 mug/g and the maximum CO(2) evolution and O(2)
      consumption rates reached 0.04 and 0.085 mmol/g-h, respectively. Polysaccharide
      content decreased approximately 50% while lignin content remained unchanged.
      Three regions of the FTIR spectra were used for quantification: 1070-974, 1705
      1614, and 2995-2887 cm(-1), which correspond to polysaccharides and aromatic and
      aliphatic compounds, respectively. The actual spectra quantification consisted of
      peak identification using a second derivative and curve fitting technique,
      followed by normalization using the internal standard CaCO(3). The results
      obtained with the spectra quantification technique was then compared to commonly
      used wet chemistry extraction procedures. Reasonable correlation between the two
      techniques was obtained. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629946
TI  - Dependence of mycelial morphology on impeller type and agitation intensity.
AB  - The influence of the agitation conditions on the morphology of Penicillium
      chrysogenum (freely dispersed and aggregated forms) was examined using radial
      (Rushton turbines and paddles), axial (pitched blades, propeller, and Prochem
      Maxflow T), and counterflow impellers (Intermig). Culture broth was taken from a
      continuous fermentation at steady state and was agitated for 30 min in an
      ungassed vessel of 1.4-L working volume. The power inputs per unit volume of
      liquid in the tank, P/V(L), ranged from 0.6 to 6 kW/m(3). Image analysis was used
      to measure mycelial morphology. To characterize the intensity of the damage
      caused by different impellers, the mean total hyphal length (freely dispersed
      form) and the mean projected area (all dispersed types, i.e., also including
      aggregates) were used. [In this study, breakage of aggregates was taken into
      account quantitatively for the first time.]At 1.4-L scale and a given P/V(L),
      changes in the morphology depended significantly on the impeller geometry.
      However, the morphological data (obtained with different geometries and various
      P/V(L)) could be correlated on the basis of equal tip speed and two other, less
      simple, mixing parameters. One is based on the specific energy dissipation rate
      in the impeller region, which is simply related to P/V(L) and particular impeller
      geometrical parameters. The other which is developed in this study is based on a
      combination of the specific energy dissipation rate in the impeller swept volume
      and the frequency of mycelial circulation through that volume. For convenience,
      the function arising from this concept is called the "energy
      dissipation/circulation" function.To test the broader validity of these
      correlations, scale-up experiments were carried out in mixing tanks of 1.4, 20,
      and 180 L using a Rushton turbine and broth from a fed-batch fermentation. The
      energy dissipation/circulation function was a reasonable correlating parameter
      for hyphal damage over this range of scales, whereas tip speed, P/V(L), and
      specific energy dissipation rate in the impeller region were poor. Two forms of
      the energy dissipation/circulation function were considered, one of which
      additionally allowed for the numbers of vortices behind the blades of each
      impeller type. Although both forms were successful at correlating the data for
      the standard impeller designs considered here, there was preliminary evidence
      that allowing for the vortices would be valuable. (c) 1996 John Wiley & Sons,
      Inc.

PMID- 18629947
TI  - A metabolic model for biological phosphorus removal by denitrifying organisms.
AB  - A metabolic model for biological phosphorus removal under denitrifying conditions
      has been established. The model is based on previous work with aerobic phosphorus
      removal. The form of the kinetic equations used is the same as for the aerobic
      model. The main difference is the value of P/NADH(2) ratio in the electron
      transport phosphorylation with nitrate (delta(N)). This value was determined
      independently from batch tests with an enriched culture of denitrifying
      phosphorus-removing bacteria. The measured delta(N) was approximately 1.0 mol
      ATP/mol NADH(2). This indicates that the energy production efficiency with
      nitrate compared to oxygen is approximately 40% lower. These batch tests were
      also used to identify a proper set of kinetic parameters. The obtained model was
      subsequently applied for the simulation of cyclic behavior in an anaerobic-anoxic
      sequencing batch reactor at different biomass retention times. The simulation
      results showed that the metabolic model can be used successfully for the
      denitrifying dephosphatation process. The obtained kinetic parameters for
      denitrifying enrichment cultures, however, deviated from those obtained for the
      aerobic enrichment cultures. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629948
TI  - Rational scale-up of a baculovirus-insect cell batch process based on medium
      nutritional depth.
AB  - We have developed a serum-free cell culture process utilizing a recombinant
      baculovirus (AcNPV) expression vector to infect Trichoplusia ni insect cells for
      the production of the human lysosomal enzyme, glucocerebrosidase. The enzyme,
      which is harvested as a secreted protein in this process, can serve as a
      replacement therapy for the genetic deficiency Gaucher disease. In the course of
      pilot scale-up of a batch glucocerebrosidase process from 25-mL working volume
      shaker flask units to 25-L working volume stirred bioreactor units, a semi
      empirical model was developed for the rational determination of scaleable process
      parameters, including host cell density at infection, multiplicity of infection
      (MOI), and harvest time. A key assumption of the model is that maximum protein
      production is limited by the serum-free medium's nutritional capacity, which can,
      in turn, be determined from the growth of uninfected cells. For the host
      cell/medium combination used in this study, the nutritional limit was determined
      to be 1.3 x 10(7) to 1.7 x 10(7) viable-cell-days/mL. Based on this, the model
      predicts that optimal protein expression is consistent with a 4-day batch process
      where the host cell density at the time of infection is 1.5 x 10(6) to 2.0 x
      10(6) cells/mL and the MOI is 0.09-0.3. These parameters were empirically
      confirmed to give the highest achievable batch product yield, first in shaker
      flasks and then at larger scales. The low MOI allows at least one population
      doubling to take place post viral addition, so that the effective infected cell
      density producing product generally exceeds 4 x 10(6) cells/mL. It was also
      interesting to note that this process consistently achieved the same level of
      maximum protein production at the 25-L bioreactor scale in 4 days compared to 5
      days at the shaker flask scale. This may be attributable to better control of the
      culture environment in the bioreactor. Unlike some other lepidopteran insect
      cells, such as Sf-9, T. ni cells were found to produce significant levels of the
      inhibitory metabolites ammonia and lactate. Our results suggest that reduction
      and/or removal of inhibitory metabolites might be beneficial for infection of
      high-density cultures of these cells and might also facilitate application of
      more sophisticated culture strategies, including fed-batch. (c) 1996 John Wiley &
      Sons, Inc.

PMID- 18629949
TI  - Regulatory effects of cellular nicotinamide nucleotides and enzyme activities on
      poly(3-hydroxybutyrate) synthesis in recombinant Escherichia coli.
AB  - Regulatory roles of nicotinamide nucleotides and three key enzymes, beta
      ketothiolase (KT), NADPH-dependent acetoacetyl-CoA reductase (AAR), and citrate
      synthase (CS), on poly(3-hydroxybutyrate) (PHB) synthesis in recombinant
      Escherichia coli harboring a plasmid containing the Alcaligenes eutrophus
      polyhydroxyalkanoate (PHA) biosynthesis genes were examined. Cells were grown in
      various media and were subsequently compared for PHB concentration, PHB content,
      the activities of the key enzymes, and the levels of nicotinamide nucleotides.
      Cells of recombinant E. coli accumulated the largest amount of PHB in LB+glucose
      medium among those tested. PHB synthesis was not enhanced by limiting inorganic
      ions. The activity of CS, which competes with KT for acetyl-CoA, was lower when
      cells were grown in LB+glucose compared with other media. The NADPH level and the
      NADPH/NADP ratio were high in LB+glucose. Examination of the time profiles of the
      specific PHB synthesis rate, key enzyme activities, and the levels of
      nicotinamide nucleotides showed that PHB synthesis is most significantly affected
      by the NADPH level. Even though the NADH level and the NADH/NAD ratio were also
      high during the synthesis of PHB, no direct evidence of their positive effect on
      PHB synthesis was found. Low activity of CS was beneficial for PHB synthesis due
      to the availability of more acetyl-CoA to PHB biosynthetic pathway. In
      recombinant E. coli, the level of NADPH and/or the NADPH/NADP ratio seem to be
      the most critical factor regulating the activity of AAR and, subsequently, PHB
      synthesis. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629950
TI  - Use of the abiotic proton balance for determining linear relations among net
      conversion rates of primary metabolites in fermentation processes.
AB  - Linear relations among net conversion rates of primary metabolites in
      fermentation processes can be determined by using the macroscopic or pathway
      balancing methods. It is shown that the process observability can be improved by
      incorporating both the abiotic proton balance and the pH control reagent addition
      rate measurement into the balancing methods. (c) 1996 John Wiley & Sons, Inc.

PMID- 18629951
TI  - Demonstration of pH control in a commercial immobilized glucose isomerase.
AB  - The synthesis of a variety of important biochemicals involves multistep enzyme
      catalyzed reactions. In many cases, the optimal operating pH is much different
      for the individual enzymatic steps of such synthesis reactions. Yet, it may be
      beneficial if such reaction steps are combined or paired, allowing them to occur
      simultaneously, in proximity to one another, and at their respective optimal pH.
      This can be achieved by separating the micro-environments of the two steps of a
      reaction pathway using a thin urease layer that catalyzes an ammonia-forming
      reaction. In this article, the pH control system in a commercial immobilized
      glucose (xylose) isomerase pellet, which has an optimal pH of 7.5, is
      demonstrated. This system allows the glucose isomerase to have near its optimal
      pH activity when immersed in a bulk solution of pH 4.6. A theoretical analysis is
      also given for the effective fraction of the immobilized glucose isomerase, which
      remains active when the bulk pH is at 4.6 in the presence of 20 mM urea versus
      when the bulk pH is at its optimal pH of 7.5. Both theoretical and experimental
      results show that this pH control system works well in this case. (c) 1996 John
      Wiley & Sons, Inc.

PMID- 18629952
TI  - Copper binding and release by immobilized transferrin: a new approach to heavy
      metal removal and recovery.
AB  - Recently these laboratories have demonstrated that it is possible to use proteins
      as efficient, selective agents for heavy metal removal and recovery. In this
      study, transferrin was chemically bound to an insoluble support. The ability of
      immobilized transferrin to produce clean water was demonstrated. Copper loading
      was independent of feed concentration. The loaded copper could be readily eluted
      and concentrated into the gram per liter range. The mechanism of copper release
      was studied. It was shown that release was dependent on pH and the chelating
      ability of the stripping agent. Metal release occurred slowly at pH < 7. However,
      at low pH in the presence of a chelator, metal removal occurred much more
      efficiently. The binding constant of copper to immobilized transferrin was
      determined as a function of pH. This information was used to model metal binding
      and release to the protein/support matrix. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629953
TI  - Fouling effects of yeast culture with antifoam agents on microfilters.
AB  - The fouling effects of yeast fermentation broths of Candida utilis in the
      presence of various commercial antifoam agents (PPG2000, B5600, and G832) up to
      4.0 mL/L were studied, using Millipore polyvinylidene fluoride 0.22-microm
      hydrophilic membranes (GVWP), in a stirred-cell system at 50 kPa and 700 rpm.
      PPG2000, which has a low value of work of adhesion (W(a) of 0.81 mN/m), gave a
      steady flux of broth of 29 L/(h m(2)) and was found to have no significant
      fouling effect on the microfiltration of broth. G832, which has a high W(a),
      (26.0 mN/m) reduced the flux of the broth to 17 L/(h m(2)); i.e., by 42% when
      only 1.0 mL/L was used. However, B5600, which has a W(a) of 14.3 mN/m, was found
      to enhance the flux of broth to 54 L/(h m(2)); i.e., by 86%, due to the
      preferential adsorption of the B5600 components onto the hydrophobic cell
      contents released. These results were reinforced by the depressurization
      experiments performed with both hydrophilic (GVWP) and hydrophobic (GVHP)
      membranes, using both young and aged broths. B5600 was found to be the optimum
      antifoam agent in this study in terms of membrane performance and defoaming
      efficiency. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629954
TI  - Alginate oligosaccharides as enhancers of penicillin production in cultures of
      penicillium chrysogenum.
AB  - Oligosaccharide fragments were prepared by partial acid hydrolysis of sodium
      alginate and consisted of oligomannuronate (OM) and oligoguluronate (OG) blocks.
      Effects of the OM and OG blocks on penicillin G production by P. chrysogenum were
      investigated. The oligosaccharides were found to cause significant increases in
      penicillin G yields. OM blocks at concentrations 10 to 100 microg/mL were used to
      further evaluate the effects of the oligosaccharides, and were found to enhance
      the production of penicillin G in shaken flask cultures of P. chrysogenum P2
      (high penicillin producer) and NRRL 1951 (low penicillin producer) at the test
      concentrations. There was an approximately 50% maximum increase in penicillin G
      yield from biomass in P. chrysogenum P2 cultures and 150% in P. chrysogenum NRRL
      1951 cultures, when compared to control cultures without the oligosaccharides.
      (c) 1997 John Wiley & Sons, Inc.

PMID- 18629955
TI  - Alcohol fermentation of starch by a genetic recombinant yeast having glucoamylase
      activity.
AB  - Alcohol fermentation of starch was investigated using a direct starch fermenting
      yeast, Saccharomyces cerevisiae SR93, constructed by integrating a glucoamylase
      producing gene (STA1) into the chromosome of Saccharomyces cerevisiae SH1089. The
      glucoamylase was constitutively produced by the recombinant yeast. The ethanol
      concentration produced by the recombinant yeast was 14.3 g/L which was about 1.5
      fold higher than by the conventional mixed culture using an amylolytic
      microorganism and a fermenting microorganism. About 60% of the starch was
      converted into ethanol by the recombinant yeast, and the ethanol yield reached
      its maximum value of 0.48 at the initial starch concentration of 50 g/L. The fed
      batch culture, which maintains the starch concentration in the range of 30 to 50
      g/L, was used to produce a large amount of ethanol from starch. The amount of
      ethanol produced in the fed-batch culture increased about 20% compared to the
      batch culture. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629956
TI  - Effect of organic solvents on enantioselectivity of protease catalysis.
AB  - The protease-catalyzed transesterifications between N-trifluoroacetyl-DL
      phenylalanine 2,2,2-trifluoroethyl ester and 1-propanol were studied in a variety
      of anhydrous organic solvents at 30 degrees C. The protease preparations
      lyophilized from phosphate buffer solutions (pH 8.0) were used as catalysts. The
      organic solvent affected both rate of reaction and enantioselectivity
      differently. Proteases such as Aspergillus oryzae protease, subtilisin Carlsberg,
      and subtilisin BPN' always preferred the L-enantiomer in both hydrophilic and
      hydrophobic solvents, indicating no inversion of the L-specificity in hydrophobic
      solvents such as toluene. However, enantioselectivity was rather poor, with E
      (enantiomeric ratio) values not exceeding even one order of magnitude except for
      acetonitrile. There was a weak inverse correlation between E values of subtilisin
      Carlsberg and solvent hydrophobicity (logP). Acetonitrile was a preferable
      solvent in terms of both rate of reaction and enantioselectivity (E= 15 to 25)
      for processing L-amino acid derivatives in organic media. Organic solvents
      generally have potential advantages of processing D-amino acid derivatives. (c)
      1997 John Wiley & Sons, Inc.

PMID- 18629957
TI  - Performance of a sulfide-oxidizing expanded-bed reactor supplied with dissolved
      oxygen.
AB  - The performance of a new sulfide-oxidizing, expanded-bed bioreactor is described.
      To stimulate the formation of well-settleable sulfur sludge, which comprises
      active sulfide-oxidizing bacterial biomass and elemental sulfur, the aeration of
      the liquid phase and the oxidation of sulfide to elemental sulfur are spatially
      separated. The liquid phase is aerated in a vessel and subsequently recirculated
      to the sulfide-oxidizing bioreactor. In this manner, turbulencies due to aeration
      of the liquid phase in the bioreactor are avoided. It appeared that, under
      autotrophic conditions, almost all biomass present in the reactor will be
      immobilized within the sulfur sludge which consists mainly of elemental sulfur
      (92%) and biomass (2.5%). The particles formed have a diameter of up to 3 mm and
      can easily be grinded down. Within time, the sulfur sludge obtained excellent
      settling properties; e.g., after 50 days of operation, 90% of the sludge settles
      down at a velocity above 25 m h(-1) while 10% of the sludge had a sedimentation
      velocity higher than 108 m h(-1). Because the biomass is retained in the reactor,
      higher sulfide loading rates may be applied than to a conventional "free-cell"
      suspension. The maximum sulfide-loading rate reached was 14 g HS(-) L(-1) d(-1),
      whereas for a free-cell suspension a maximum loading rate of 6 g HS(-) L(-1) d(
      1) was found. At higher loading rates, the upward velocities of the aerated
      suspension became too high so that sulfur sludge accumulated in the settling zone
      on top of the reactor. When the influent was supplemented with volatile fatty
      acids, heterotrophic sulfur and sulfate reducing bacteria, and possibly also
      (facultatively) heterotrophic Thiobacilli, accumulated within the sludge. This
      led to a serious deterioration of the system; i.e., the sulfur formed was
      increasingly reduced to sulfide, and also the formation rate of sulfur sludge
      declined. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629958
TI  - Stability of nicotinamide adenine dinucleotide immobilized to cyanogen bromide
      activated agarose.
AB  - The stability of NAD(H) immobilized to a crosslinked agarose support
      (Sepharose(R)-4B) was examined in buffer solutions at a pH of 7.0 and 8.5.
      Specifically, this study investigated particle attrition and ligand leakage rates
      from a cyanogen bromide activated agarose support. Particle attrition did not
      occur under the experimental conditions. Ligand leakage rates were found to be
      first order in immobilized ligand concentration with two labile populations of
      ligand. The two-population model is consistent with the cyanogen bromide coupling
      chemistry, which results in both an isourea and imidocarbonate ligand linkage.
      The rate of ligand leakage was found to occur over a time scale of days, with
      first order rate constants ranging from 0.007 to 0.15 d(-1), depending on
      solution pH. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629959
TI  - Design and study of peptide-ligand affinity chromatography adsorbents:
      application to the case of trypsin purification from bovine pancreas.
AB  - The purification of trypsin from bovine pancreas was employed in a case study
      concerning the design and optimization of peptide-ligand adsorbents for affinity
      chromatography. Four purpose-designed tripeptide-ligands were chemically
      synthesized (>95% pure), exhibiting an Arg residue as their C-terminal (site
      P(1)) for trypsin bio-recognition, a Pro or Ala in site P(2), and a Thr or Val in
      site P(3). Each tripeptide-ligand was immobilized via its N-terminal amino group
      on Ultrogel A6R agarose gel, which was previously activated with low
      concentrations of cyanuric chloride (10.5 to 42.5 micromol/g gel). Well over 90%
      of the peptide used was immobilized. Three different concentrations were
      investigated for every immobilized tripeptide-ligand, 3.5, 7.0, and 14 micromol/g
      gel. The K(D) values of immobilized tripeptide-trypsin complexes were determined
      as well as the purifying performance and the trypsin-binding capacity of the
      affinity adsorbents. The K(D) values determined were in good agreement with the
      trypsin purification performance of the respective affinity adsorbents. The
      tripeptide sequence H-TPR-OH displayed the highest affinity for trypsin (K(D) 8.7
      microM), whereas the sequence H-TAR-OH displayed the lowest (K(D) 38 microM).
      Dipeptide-ligands have failed to bind trypsin. When the ligand H-TPR-OH was
      immobilized via its N-terminal on agarose, at a concentration of 14 micromol/g
      gel, it produced the most effective affinity chromatography adsorbent. This
      adsorbent exhibited high trypsin-binding capacity (approximately 310,000 BAEE
      units/mL of adsorbent); furthermore, it purified trypsin from pancreatic crude
      extract to a specific activity of 15,200 BAEE units/mg (tenfold purification),
      and 82% yield. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629960
TI  - A Kalman filter algorithm and monitoring apparatus for at-line control of
      fractional protein precipitation.
AB  - Downstream processing operations are often carried out blind in the process
      timescale since product monitoring on-line is not common. Knowledge of the
      location and concentration of the product and key contaminants is complementary
      to other process information for process development and, if available on-line in
      conjunction with a suitable model, control. This article sets out to demonstrate
      a model describing a two-cut fractional protein precipitation process and how
      this may be used for control of the process to maximize yield in the face of
      variable process stream conditions. Estimation of the model parameters is
      achieved by means of data-fitting by least squares and in comparison prediction
      by a Kalman filter algorithm. A description and error analysis of equipment for
      at-line monitoring of the soluble product in a pilot plant environment is
      presented which includes a micro-centrifuge necessary to clarify small volumes of
      sample prior to analysis. Finally, an account of the successful implementation of
      this equipment and the Kalman filter algorithm for control at bench scale is
      given where conditions in the process stream are deliberately disturbed to test
      the control operation. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629961
TI  - Effect of acetaldehyde on Saccharomyces cerevisiae and Zymomonas mobilis
      subjected to environmental shocks.
AB  - The lag phase of Saccharomyces cerevisiae subjected to a step increase in
      temperature or ethanol concentration was reduced by as much as 60% when
      acetaldehyde was added to the medium at concentrations less than 0.1 g/L. Maximum
      specific growth rates were also substantially increased. Even greater
      proportional reductions in lag time due to acetaldehyde addition were observed
      for ethanol-shocked cultures of Zymomonas mobilis. Acetaldehyde had no effect on
      S. cerevisiae cultures started from stationary phase inocula in the absence of
      environmental shock and its lag-reducing effects were greater in complex medium
      than in a defined synthetic medium. Acetaldehyde reacted strongly with the
      ingredients of complex culture media. It is proposed that the effect of added
      acetaldehyde may be to compensate for the inability of cells to maintain
      transmembrane acetaldehyde gradients following an environmental shock. (c) 1997
      John Wiley & Sons, Inc.

PMID- 18629962
TI  - Preparation of magnetically susceptible polyacrylamide/magnetite beads for use in
      magnetically stabilized fluidized bed chromatography.
AB  - Spherical polyacrylamide/magnetite (PAM) composite beads, suitable for use in a
      magnetically stabilized fluidized bed (MSFB), were manufactured by a suspension
      polymerization method. Yield of beads depended on the type and concentration of
      buffer used during polymerization as well as the pH. More stabilizer was needed
      to prevent bead agglomeration as magnetite concentration increased. Bead diameter
      ranged from less than 60 to 600 microm, depending on reaction conditions, and the
      bead mean diameter and size distribution decreased with increasing impeller
      speed. The density and roundness factor of the beads were 1.19 +/- 0.02 g cm(-3)
      and 1.08 +/- 0.03, respectively. The beads had high magnetization at a low
      applied magnetic field strength (60 mT at 75 kA m(-1)) and retained little
      residual magnetization (<2 mT) after the field was removed. Incorporation of
      magnetite did not significantly affect the physical strength of the beads: the
      beads' average elastic modulus was 14 +/- 4 kPa, similar to reported values for
      polyacrylamide gels (15.8 kPa). The beads were stable in a range of buffers from
      pH 1 to 10 and were resistant to microbial degradation. The fluidization and
      stabilization behavior of the beads was examined in a bench-scale MSFB. The
      minimum fluidization velocity (U(mf)) of the beads (0.035 mm s(-1)) allowed the
      MSFB to be operated at superficial velocities close to those used in HPLC
      systems. Against expectations, at high superficial velocities, the stabilized bed
      of the MSFB had a greater expansion than the unstabilized bed. The PAM beads
      could be derivatized and activated for soybean trypsin inhibitor immobilization
      by a standard carbodiimide method, and the affinity separation of trypsin from
      chymotrypsin was demonstrated. The PAM beads show excellent potential for use in
      MSFB chromatography. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629963
TI  - Abrasion of suspended biofilm pellets in airlift reactors: importance of shape,
      structure, and particle concentrations.
AB  - The detachment of biomass from suspended biofilm pellets in three-phase internal
      loop airlift reactors was investigated under nongrowth conditions and in the
      presence of bare carrier particles. In different sets of experiments, the
      concentrations of biofilm pellets and bare carrier particles were varied
      independently. Gas hold-up, bubble size, and general flow pattern were strongly
      influenced by changes in volume fractions of biofilm pellets and bare carrier
      particles. In spite of this, the rate of biomass detachment was found to be
      linear with both the concentration of biofilm pellets and the bare carrier
      concentration up to a solids hold-up of 30%. This implies that the detachment
      rate was dominated by collisions between biofilm pellets and bare carrier
      particles. These collisions caused an on-going abrasion of the biofilm pellets,
      leading to a reduction in pellet volume. Breakage of the biofilm pellets was
      negligible. The biofilm pellets were essentially ellipsoidal, which made three
      dimensional size determination necessary. Calculating particle volumes from two
      dimensional image analysis measurements and assuming a spherical shape led to
      serious errors. The abrasion rate was not equal on all sides of the biofilm
      pellets, resulting in an increasing flattening of the pellets. This flattening
      was oriented with the basalt carrier inside the biofilm and independent of the
      absolute abrasion rate. These observations suggest that the collisions causing
      abrasion are somehow oriented. The internal structure of the biofilms showed two
      layers, a cell-dense outer layer and an interior with a low biomass density.
      Taking this density gradient into account, the washout of detached biomass
      matched observed changes in volume of the biofilm pellets. No gradient in biofilm
      strength with biofilm depth was indicated. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629964
TI  - Bioremediation of uranium-bearing wastewater: biochemical and chemical factors
      influencing bioprocess application.
AB  - A biotechnological process for the removal of heavy metals from aqueous solution
      utilizes enzymatically liberated phosphate ligand which precipitates with heavy
      metals (M) as cell-bound MHPO(4). The enzyme, a phosphatase, obeys Michaelis
      Menten kinetics in resting and immobilized cells; an integrated form of the
      Michaelis-Menten equation was used to calculate the apparent K(m) (K(m app.)) as
      operating in immobilized cells in flow-through columns by a ratio method based on
      the use of two enzyme loadings (E(o1), E(o2)) or two input substrate
      concentrations (S(o1), S(o2)). The calculated K(m app.) (4.08 mM) was substituted
      into an equation to describe the removal of metals by immobilized cells. In
      operation the activity of the bioreactor was in accordance with that predicted
      mathematically, within 10%. The initial tests were done at neutral pH, whereas
      the pH of industrial wastewaters is often low; an increase in the K(m app.) at
      low pH was found in previous studies. Immobilized cells were challenged with
      acidic mine drainage wastewaters, where the limiting factors were chemical and
      not biochemical. Bioreactors initially lost activity in this water, but recovered
      to remove uranyl ion with more than 70% efficiency under steady-state conditions
      in the presence of competing cations and anions. Possible reasons for the
      bioreactor recovery are chemical crystallization factors. (c) 1997 John Wiley &
      Sons, Inc.

PMID- 18629965
TI  - Isoelectrically trapped enzymatic bioreactors in a multimembrane cell coupled to
      an electric field: theoretical modeling and experimental validation with urease.
AB  - A novel type of immobilized enzyme reactor operating under an electric field is
      here reported: a multicompartment immobilized enzyme reactor (MIER). In this
      experimental set-up, the enzyme and zwitterionic buffering ions are trapped in
      between two isoelectric membranes, having isoelectric point (pl) values so far
      apart as to trap the enzyme by an isoelectric mechanism, while allowing operation
      at pH optima, even when the latter pH value is quite removed from the enzyme pl.
      As an example, urease (pl 4.9) is trapped between a pl 4.0 and a pl 8.0
      membranes, thus permitting operation (via suitable amphoteric ions buffering at
      pH 7.5) at the pH of optimum of activity (pH 7.5). The charged product (ammonium
      ions) quickly leaves the enzyme chamber under the influence of the electric
      field, thus allowing sustained activity for much longer time periods than in
      conventional reactors. As an example, while in a batch reactor 90% of original
      enzyme activity is lost in 200 min, only 2% activity is lost in the same period
      in the MIER reactor. As an additional bonus, the MIER reactor allows conversion
      rates of approximately 95% in a wide range of substrate concentrations, whereas
      batch-type reactors rarely achieve better than 50% conversion under comparable
      experimental conditions. (c) 1997 John Wiley & Sons, Inc.

PMID- 18629966
TI  - [Prevention and reoperative therapy for locally recurrent rectal cancer].

PMID- 18629967
TI  - Darunavir: after multiple antiretroviral treatment failure: another option.
AB  - In HIV-infected patients with multiple antiretroviral treatment failure, two
      trials show that adding darunavir + ritonavir to optimised antiretroviral
      treatment is more effective than adding other protease inhibitors. Clinical
      trials, involving relatively few patients, revealed no significant adverse
      effects that had not previously been seen with HIV protease inhibitors. There is
      a high risk of drug interactions with darunavir.

PMID- 18629968
TI  - Nicorandil: serious gastrointestinal ulceration.
AB  - (1) Nicorandil is a vasodilator with limited efficacy, marketed for symptomatic
      relief of angina pectoris. Oral ulcerations, sometimes quite large, are an
      adverse effect of nicorandil that has been known since the 1990s. Cases of
      painful anal ulceration were reported later. (2) More recently, it has emerged
      that nicorandil can also cause very painful chronic ulceration of the colon and
      small intestine. Painful parastomal ulceration has also been reported in patients
      with ileostomies or colectomies. (3) Gastrointestinal ulceration has been
      reported from the mouth to the perineum. It is sometimes associated with skin
      ulcers. (4) In some cases the lesions are sufficiently extensive and refractory
      to warrant surgery (colostomy) or immunosuppressant treatment. However, simply
      withdrawing nicorandil generally leads to recovery with a few weeks. (5)
      Nicorandil should not be considered a standard treatment for angina pectoris. It
      is better to choose another drug such as a betablocker. Nicorandil must be
      withdrawn if cutaneous or gastrointestinal ulceration occurs.

PMID- 18629969
TI  - Sodium phosphates and colonoscopy: renal failure.
AB  - Sodium phosphate solutions used for bowel cleansing before colonoscopy increase
      the risk of renal failure, especially in the elderly or in patients treated with
      angiotensin-converting enzyme inhibitors or other drugs that can affect renal
      function.

PMID- 18629970
TI  - Dextropropoxyphene: welcome withdrawal from a French hospital's formulary.
AB  - Decision to exclude dextropropoxyphene from the list of drugs available at
      Toulouse University Hospital: more prescriptions of paracetamol as monotherapy
      and fewer prescriptions of step-2 analgesics.

PMID- 18629971
TI  - Varenicline: depression and suicide. Nicotine is a safer option.

PMID- 18629972
TI  - The transatlantic slave trade: a new census.

PMID- 18629973
TI  - Transoceanic mortality: the slave trade in comparative perspective.

PMID- 18629974
TI  - Colchicine: fatal pancytopenia at therapeutic doses. Fatal pancytopenia
      associated with colchicine, a drug with a narrow therapeutic margin.

PMID- 18629975
TI  - Threading the needle: mimicking natural toroidal catalysts.

PMID- 18629976
TI  - Ultrafast electron crystallography: the dawn of a new era.

PMID- 18629977
TI  - Controversy in chemistry: what counts as evidence?--Two studies in molecular
      structure.

PMID- 18629978
TI  - Superfluid helium droplets: a uniquely cold nanomatrix for molecules and
      molecular complexes.
AB  - Herein, recent experiments on the spectroscopy and chemical reactions of
      molecules and complexes embedded in helium droplets are reviewed. In the
      droplets, a high spectroscopic resolution, which is comparable to the gas phase
      is achieved, while an isothermal low-temperature environment is maintained by
      evaporative cooling at T =0.37 K (4He droplets) or 0.15 K (3He droplets), lower
      than possible in most solid matrices. Thus the helium-droplet technique combines
      the benefits of both the gas phase and the classical matrix-isolation techniques.
      Most important, the superfluid helium facilitates binary encounters, and absorbs
      the released binding energy upon recombination. Thus the droplet can be viewed as
      an isothermal nanoscopic reactor, which isolates single molecules, clusters, or
      even a single reactive encounter at ultralow temperatures.

PMID- 18629979
TI  - A molecular mechanism of hysteresis in clay swelling.

PMID- 18629981
TI  - Synthesis and characterization of a quasi-one-coordinate lead cation.

PMID- 18629980
TI  - Catalytic asymmetric acylation of (silyloxy)nitrile anions.

PMID- 18629982
TI  - Total synthesis of (-)-galanthamine by remote asymmetric induction.

PMID- 18629983
TI  - A lockable light-driven molecular shuttle with a fluorescent signal.

PMID- 18629984
TI  - A new dirhodium(II) carboxamidate complex as a chiral Lewis acid catalyst for
      enantioselective hetero-Diels-Alder reactions.

PMID- 18629985
TI  - Formal [3+2] addition of acceptor-substituted cyclopropylmethylsilanes with aryl
      acetylenes.

PMID- 18629986
TI  - High-content peptide microarrays for deciphering kinase specificity and biology.

PMID- 18629987
TI  - Sceptrin as a potential biosynthetic precursor to complex pyrrole-imidazole
      alkaloids: the total synthesis of ageliferin.

PMID- 18629988
TI  - Au32: a 24-carat golden fullerene.

PMID- 18629990
TI  - Immobilization of a metallo schiff base into a microporous coordination polymer.

PMID- 18629989
TI  - An intramolecular organocatalytic cyclopropanation reaction.

PMID- 18629991
TI  - Consecutive cyclic pentapeptide modules form short alpha-helices that are very
      stable to water and denaturants.

PMID- 18629992
TI  - Water-soluble supramolecular fullerene assembly mediated by metallobridged beta
      cyclodextrins.

PMID- 18629993
TI  - Direct evidence for a furtive state in the degradation of carbasalatum calcicum.

PMID- 18629994
TI  - Dissolution at the nanoscale: self-preservation of biominerals.

PMID- 18629995
TI  - Porous organic-inorganic assemblies constructed from Keggin polyoxometalate
      anions and calix[4]arene-Na+ complexes: structures and guest-sorption profiles.

PMID- 18629996
TI  - Ultrafast electron crystallography of surface structural dynamics with atomic
      scale resolution.

PMID- 18629997
TI  - Synthesis and application of fluorescence-labeled Ras-proteins for live-cell
      imaging.

PMID- 18629998
TI  - The chemistry of CaII and YbII: astoundingly similar but not equal!

PMID- 18629999
TI  - A simple approach to nonspherical electron densities by using invarioms.

PMID- 18630000
TI  - Baby's choice.

PMID- 18630001
TI  - Marion's message. The first-time women's health exam.

PMID- 18630002
TI  - VBAC & choice: many questions and a few answers.

PMID- 18630003
TI  - A father's birth story of breech twins: Tiernan Shae & Caulla Anora Mae.

PMID- 18630004
TI  - Choices.

PMID- 18630005
TI  - The spot.

PMID- 18630006
TI  - The "Rule of Ten" versus women's primal wisdom.

PMID- 18630007
TI  - Moving into feeling: the evolution of spiritual midwifery.

PMID- 18630008
TI  - Leonard's cord.

PMID- 18630009
TI  - Choice in cesarean.

PMID- 18630010
TI  - Midwifery in New York.
AB  - For many women living in New York, finding a licensed midwife to attend their
      birth at home is impossible. This article seeks to discuss the process by which
      Certified Professional Midwives (CPMs) can become licensed in New York and to
      explain a barriers to practicing outside the hospital. It will also explore what
      is being done to work toward making home-birth a more easily accessible option in
      New York.

PMID- 18630011
TI  - 2 homebirths, 14 minutes apart.

PMID- 18630012
TI  - What would an Evidence-based statement on homebirths from ACOG say?
AB  - On February 6, 2008, the American College of Obstetricians and Gynecologists
      (ACOG) released a new homebirth statement, similar to their previous homebirth
      statements, stating that all women would be better off being delivered in
      hospital. This article presents what an evidence-based ACOG statement on
      homebirths would say and includes the responses of 15 midwives and doulas to the
      new ACOG Homebirth statement.

PMID- 18630013
TI  - Working with your naturopathic doctor in perinatal care--our philosophy: a
      meeting of the minds between midwifery and naturopathic medicine.

PMID- 18630014
TI  - Why I'm a midwife.

PMID- 18630015
TI  - An unexpected natural birth.

PMID- 18630016
TI  - The light in the grey area: a wild woman's view of caesarean surgery.

PMID- 18630017
TI  - Mana from Heaven: a midwife's experiences of spirituality in childbirth.

PMID- 18630018
TI  - Homebirth after cesarean: the myth & the reality.

PMID- 18630019
TI  - Doula by default.

PMID- 18630020
TI  - An unconditional love.

PMID- 18630021
TI  - Negotiating with the insurer for fair payment.

PMID- 18630022
TI  - Look to traditional midwives.

PMID- 18630023
TI  - Circle of Health International: bringing together Israeli & Palestinian midwives.

PMID- 18630024
TI  - Birth choices in Venezuela.

PMID- 18630025
TI  - Dancing to the back of the line.

PMID- 18630027
TI  - Pharmacogenetics and pharmacogenomics: the silver bullet?

PMID- 18630026
TI  - Disparities in health care--the side effect of pay-for-performance.

PMID- 18630028
TI  - Case of acute psychosis from herbal supplements.
AB  - A recent study estimates that 15.2 percent of American adults use nonprescription
      dietary supplements for weight loss. Sale of ephedrine- and ephedrine-alkaloid
      containing products was prohibited by the Food and Drug Administration in
      February 2004 after research demonstrated an increased risk of arrhythmia,
      mortality and hypertension following use of products containing these
      sympathomimetics. Subsequently, nutritional supplement manufacturers have turned
      to other products to promote weight loss. The following paper reports a case
      study of a 28-year-old woman with no prior psychiatric history who was
      hospitalized secondary to an acute psychotic episode. The patient reported
      starting several weight-loss and nutritional sports supplements approximately one
      week prior to admission. The relationship between the onset of psychosis and the
      initiation of the dietary supplements strongly suggests a correlation exists.
      Heightened consumer education regarding the contents of dietary supplements,
      along with their potential for causing adverse effects when used alone or in
      combination with other medications, is warranted. Patients who choose to take
      dietary supplements should be encouraged to inform their health care providers
      about the supplements they are taking.

PMID- 18630029
TI  - Introduction of radiology instruction throughout the medical education
      curriculum.

PMID- 18630030
TI  - Schedule II controlled substances: an update and review.

PMID- 18630031
TI  - Everything you didn't want to know about HEDIS and were afraid to ask.

PMID- 18630032
TI  - Moving to the sound of music.

PMID- 18630033
TI  - If the benefits of preventive screenings are so clear, why do so many go without?

PMID- 18630034
TI  - National health insurance coverage.

PMID- 18630035
TI  - Patient Physician Partnership proves effective: 2008 Kentucky General Assembly a
      success for medicine.

PMID- 18630036
TI  - The applicant pool: the genesis of the physician pipeline.
AB  - As medical schools across the nation consider the recent call made by the
      Association of American Medical Colleges to increase numbers of medical school
      students by 30% by 2015, it is important to explore the characteristics of the
      applicant pool. Understanding the make-up of the pool of recent applicants to the
      University of Kentucky College of Medicine can assist us in defining areas where
      the pool could be expanded in the future. Reviewing data from 2002-2006, we will
      examine the Kentucky county of origin of our applicants and matriculants. We will
      describe demographic characteristics of our applicants and matriculants with
      regard to gender, race and ethnicity, and international backgrounds. We will also
      look at factors that may discourage or dissuade prospective applicants from
      seeking admission to medical school including undergraduate grades, denial of the
      initial application to medical school, and cost considerations.

PMID- 18630037
TI  - Cost-benefit analysis on the HPV vaccine in Medicaid-enrolled females of the
      Appalachian region of Kentucky.
AB  - OBJECTIVE: The objective of this study was to determine the cost-efficiency of
      vaccinating against Human Papillomavirus (HPV) in Medicaid enrolled females of
      the Appalachian region of Kentucky (n = 49,411 females) aged 12 to 25 years,
      versus paying for the treatment of cervical cancer cases (n = 643 cases) within
      this population later in life. METHODS: In order to determine the cost of
      vaccination and cervical cancer treatment, the use of data acquired from the
      Kentucky Department of Medicaid Services (DMS) and Kentucky Cancer Registry (KCR)
      was necessary. RESULTS: Relative Risk of Appalachian Kentuckian females
      developing cervical cancer compared to their non-Appalachian counterparts is
      1.23. The total cost DMS paid to treat cervical cancer in 2005 in Appalachian
      counties was $5.95 million. The direct cost DMS paid in 2005 to treat cervical
      cancer was $960,910.95. The direct cost for the vaccine for the 2005 Medicaid
      enrolled population aged 12 to 25 in Appalachian Kentucky counties is $17.8
      million (price of $360 for the three-dose vaccine). The cost to vaccinate the
      subsequent 12-year-old cohort (n = 4,137 females, born in 1995) in the next year
      is $1.5 million. Each year similar additional costs would accrue. CONCLUSIONS:
      Implementing a prevention plan for cervical cancer that includes annually
      vaccinating Medicaid-enrolled adolescent females of the Appalachian region of
      Kentucky against HPV infection is cost-efficient for the Medicaid system when
      considering the total expenditures associated with the illness. Recognition of an
      actual cost savings would not occur for several decades as the vaccinated
      population ages.

PMID- 18630038
TI  - First home call.

PMID- 18630039
TI  - Medical family trilogy: part 3.

PMID- 18630040
TI  - [Leprosy: can the war be won?].

PMID- 18630041
TI  - [Cerebral hydatidosis].

PMID- 18630042
TI  - [Foot health in the tropics].
AB  - The foot is particularly exposed to injury and infection in the tropical areas.
      This article provides a review of the main diseases affecting the foot in the
      tropics including leprosy, ainhum, ulceration due to Mycobacterium ulcerans,
      mycetoma, chromomycosis, Kaposi's sarcoma, elephantiasis, podoconiasis,
      dracunculosis, tungiasis, syphilis and endemic treponematosis, larva migrans,
      scytalidiosis, and envenomation. Prevention is essential.

PMID- 18630043
TI  - [Ticks and human tick-borne diseases in Africa].
AB  - Ticks are obligate hematophagous arthropod parasites that feed on the blood of
      every class of vertebrates in almost every region of the world. Tick bites can
      transmit bacterial, viral and parasitic diseases to humans. In this review we
      describe ticks and human tick-borne diseases in Africa. The first part of this
      article presents elements linking the morphology and biology of these acarians as
      well as various aspects of their taxonomy and phylogeny. The next part of the
      article describes the main human tick borne diseases in Africa with particular
      focus on spotted fever group rickettsioses, relapsing fever borrelioses, and
      Crimean-Congo fever. Information is also provided on Q fever and other tick-borne
      diseases as ehrlichioses, anaplasmoses, Lyme disease, and babesiosis that can and
      do occur in Africa. Finally this article describes methods used for the
      collection and identification of ticks and for control and prevention of tick
      bites as well as essential points for early diagnosis and management of patients
      who have been bitten by ticks.

PMID- 18630044
TI  - [XXIst French-language North-South Pediatric Conference].

PMID- 18630045
TI  - [Follow-up of the first case of Mycobacterium ulcerans infection documented by
      PCR, genotyping and culture in the Republic of Congo-Brazzaville].
AB  - This article presents follow-up data from the first patient in whom Mycobacterium
      ulcerans infection (MUI) was documented by PCR, genotyping and culture in the
      Republic of Congo-Brazzaville. Findings show the importance of regular clinical
      and microbiological evaluation for the disseminated form of the disease. The
      patient was probably infected in Pointe Noire where MUI has been described but
      never documented. Culture of specimens collected before antibiotic treatment
      showed that the bacterium was sensitive to the antibiotics being administered
      (streptomycin and rifampin) and was identical to isolates from Atlantic-coast
      regions of West Africa where MUI is endemic. The patient was treated with
      streptomycin and rifampin for 12 weeks in association with surgery. During
      treatment clinical examination was performed every day and microbiological
      analysis every two weeks. The duration of follow-up from the end of specific
      antibiotic treatment was 26 months. Medical treatment failed to prevent bone
      involvement and fistulae that were treated by surgery. However medical treatment
      may have limited dissemination of the disease. Serial microbiological evaluation
      was useful to detect bone involvement in this patient, but persistent positive
      gene amplification is not a proof of active disease. This study confirms that MUI
      is still endemic in the region of Pointe Noire. This finding underlines the need
      to optimize epidemiologic surveillance, laboratory diagnostic capabilities, and
      therapeutic management in the Republic of Congo-Brazzaville.

PMID- 18630046
TI  - [Celiac disease: special features in Africa. Description of 8 cases in Djibouti
      (horn of Africa)].
AB  - Celiac disease is poorly documented in intertropical Africa. The purpose of this
      retrospective report was to describe 8 cases observed at the Groupement Medico
      Chirurgical of Bouffard Hospital in Djibouti (Horn of Africa) between January
      2003 and January 2006. There were 5 females and 3 males ranging in age from 9
      months to 17 years old (mean age: 48 months). Six patients were of Somali ethnic
      origin and two of Yemenite ethnic origin. Six were classified as middle class and
      2 as lower class. All forms were symptomatic associating constant loss of weight
      with digestive manifestations (diarrhoea and vomiting). Diagnosis of celiac
      disease was based on the presence of anti-gliadin antibodies IgA and IgG
      associated with anti-endomysium or anti-transglutaminase antibodies that were
      measured in six and two cases respectively. Gastroduodenal endoscopy performed in
      three cases including two with duodenal biopsy demonstrated villous atrophy
      associated with gross of intra-epithelial lymphocytosis. A gluten-free diet
      initiated in five patients led to clinical improvement in four cases with a
      follow-up of 8.25 months. The findings of this study in Djibouti show that celiac
      disease exists in intertropical Africa. Its presentation is quite similar to
      elsewhere but diagnosis is more difficult due to poor knowledge about the disease
      and limited diagnostic facilities. Favourable response to presumptive treatment
      by a gluten-free diet is an alternative for diagnosis especially in Djibouti
      where eating habits differ from those in industrialized countries and this type
      of diet is easier to follow.

PMID- 18630047
TI  - [Prescribing and dispensing generic drugs in the Mambere-Kadei health district of
      the Central African Republic].
AB  - Good drug prescription and distribution practices are pre-requisites for rational
      use of essential generic medications. However few studies have been conducted on
      this topic in sub-Saharan Africa especially in rural areas. The purpose of this
      study in the Mambere-Kadei health district of the Central African Republic was to
      evaluate drug use patterns with special attention to prescribing and dispensing,
      as a basis for assisting policy makers in planning and identifying intervention
      strategies. The transverse descriptive survey was undertaken in 14 public health
      facilities in the Mambere-Kadei health district. Data were collected by
      interviewing care providers and patients immediately after consultation and at
      the exit of the dispensary. The indicators recommended by the World Health
      Organization (WHO) for investigating drug use patterns in Communities were used
      for data collection. A total of 512 prescriptions were analysed. The average
      number of drugs prescribed per consultation was 3.5. Most drugs (68.6%) were
      prescribed by generic name. Antibiotic use (31.4% of consultations) was frequent
      and 29% of patients received injections. 82.1% of the drugs were compliant with
      the national essential drug list. The distribution survey showed that 79.46% of
      prescriptions were completely filled. No serious distribution errors occurred but
      21.5% of the dispensed drugs were inadequately labelled. Patients understood the
      modalities of use for 69.6% of prescribed drugs. The average consultation and
      distribution times were 8.3 and 5 minutes respectively. Excessive use of
      antibiotics and injections and blunderbuss therapy is still observed in Mambere
      Kadei. Many drugs not included on the essential drug list and non-generics are
      prescribed. Other prescription and distribution problems identified in this
      survey include poor information on drug use, inadequate labelling of dispensed
      drugs, and lack of access to standard drug use tools such as a locally adapted
      essential drug list, formularies and standard treatment guidelines. To improve
      the system, caregivers must receive more training on the rational use of
      essential generic drugs and the population must be better informed.

PMID- 18630048
TI  - [Ventricular dysfunction during acute fever in Dakar, Senegal. Clinical data and
      serological studies].
AB  - During a study, the authors observed clinical and ultrasound evidence of
      "ventricular dysfunction during acute fever" due to ue to "severe acute
      myocarditis" supports therapeutic management since 4/8 patients in this study
      were infected either by Chlamydia (CT and especially CP) or by Mycoplasma
      pneumoniae, that are both sensitive to antimicrobial therapy using macrolides.
      Five of 8 patients presented coinfection with 2 and even 3 infectious agents (CP
      enterovirus-adenovirus).

PMID- 18630049
TI  - [Evaluation of integrated management of childhood illness three years after
      implementation in a health care district in Senegal].
AB  - The strategy of Integrated Management of Childhood Illness (IMCI) has been
      recommended by both WHO and UNICEF for first-level health facilities to control
      the main childhood diseases in developing countries. In Senegal, IMCI was adopted
      in 1996 and had been implemented in several pilot health districts by the year
      2000. This study was conducted three years after implementation of IMCI in the
      Darou Mousty health district. The purpose was to evaluate determinant factors for
      implementation as well as the required skills of personnel. Evaluation was based
      on a review of IMCI records at health care facilities in the District and a
      survey to collect the opinion of healthcare workers involved in the program. All
      qualified personal, i.e. two doctors, eleven nurses and one midwife at the time
      of the survey, had received training in the IMCI approach. Although they all
      stated that this training improved their skills in managing paediatric patients,
      only 16 % used the approach on a regular basis. The most frequently reported
      reason for non-use was unwieldiness of IMCI procedures. According to IMCI
      guidelines, proper procedures were used in only 53 of the 1465 children (3.6%)
      who consulted during the study period. This low compliance rate was due to the
      inability of healthcare personnel to apply therapeutic protocols, plan
      appointments or identify emergency cases. These findings suggest that basic
      training and in-service courses must place greater emphasis on IMCI procedures
      and that regular supervision is needed to optimize this strategy in Senegal.

PMID- 18630050
TI  - [Pulmonary tuberculosis in infants in Brazzaville, Congo. A review of 117 cases].
AB  - Little information is available on pulmonary tuberculosis in infants in sub
      Saharan Africa. This retrospective study was conducted in infants ranging in age
      from 1 to 23 months admitted to the Paediatric Departments of the University
      Hospital Centre in Brazzaville, Congo for pulmonary tuberculosis between January
      1, 1999 and July 1, 2004. Tuberculosis was diagnosed on the basis of
      epidemiological, clinical, radiological, and follow-up data. All children over 12
      months old underwent HIV testing. In case of positive test results, children
      between the ages of 12 and 18 months were retested after the age of 18 months. Of
      a total of 803 children admitted for tuberculosis during the study period, 117
      (14.6%) were under the age of 24 months (53% males). Mean age was 17.5 months.
      The BCG test was mentioned in 75.2% of cases. Determination of the contagion in
      50.4% of cases indicated that transmission was intrafamilial in 69.3% of cases.
      The mean delay for hospitalization was 2.6 months (range, 21 days to 16 months).
      Eighty-one patients (69.2%) presented severe malnutrition. Intrathoracic forms
      accounted for most cases with bronchopneumopathy (72.6%) and mediastinal
      adenopathy (40.2%). The incidence of bronchopneumonopathy and isolated forms was
      significantly higher in children over one year old than in children under one
      year old: 78.3% versus 21.7 % (p<0.01) and 62.8% versus 37.2% (p<0.001)
      respectively. A total of 35 children (43.8%) over the age of 12 months presented
      HIV infection. In comparison with HIV-negative children, HIV-positive children
      were more likely to present malnutrition and presented a statistically higher
      incidence of mediastinal adenopathy and multifocal forms. All associated
      extrathoracic lesions (21.4% of cases) occurred in HIV-positive children. Outcome
      was favourable in all HIV-negative children while 7 HIV-positive children (20%)
      died during treatment. Pulmonary tuberculosis in infants in Brazzaville is
      characterized by frequent association with HIV infection and prognosis is more
      severe in case of HIV co-infection.

PMID- 18630051
TI  - [Cutaneous tuberculosis: a pediatric case in Madagascar].
AB  - Cutaneous manifestation of tuberculosis is still observed in countries with high
      endemicity of tuberculosis such as Madagascar. The purpose of this report is to
      describe a case of nodular type cutaneous tuberculosis located in the subclavian
      region of a 5-month-old child living in Antananarivo, Madagascar. In absence of
      bacteriological evidence, diagnosis was based on epidemiological, clinical and
      histological findings. Treatment was successful using standard antituberculosis
      therapy. This case illustrates the diagnostic pitfalls associated with this type
      of tuberculosis.

PMID- 18630052
TI  - [Betel quid and oral cancer: case report].
AB  - Betel quid chewing is a major cause of oral cancers in Asia. Practitioners must
      be able to recognize premalignant lesions. Cessation of betel quid use and
      preventive treatment must be recommended. Primary prevention will be difficult
      because of the traditional nature and commercial importance of this old habit.

PMID- 18630053
TI  - [Left atrial mass observed in a patient in Abidjan, Ivory Coast].
AB  - The purpose of this report is to present a case involving a tumor-like mass in
      the left atrium of a 27-year-old woman in Abidjan, Ivory Coast. The mass was
      discovered by echocardiography carried out after cardiomegaly was detected by
      roentgenography performed in the context of debilitated general condition, fever
      and positive serology for HIV1. The patient responded favorably to anti
      tuberculosis treatment with complete regression of the mass and improvement of
      general condition. Based on this outcome, the most likely diagnosis was cardiac
      tuberculoma, a rare complication of tuberculosis.

PMID- 18630054
TI  - [Conclusions and recommendations of a WHO expert consultation meeting on iron
      supplementation for infants and young children in malaria endemic areas].
AB  - This article presents the results of an expert consultation meeting aimed at
      evaluating the safety and public health implications of administering
      supplemental iron to infants and young children in malaria-endemic areas.
      Participants at this meeting that took place in Lyon, France on June 12-14, 2006
      reached consensus on several important issues related to iron supplementation for
      infants and young children in malaria-endemic areas. The conclusions in this
      report apply specifically to regions where malaria is endemic.

PMID- 18630056
TI  - [Toxidermia during antiretroviral therapy in Conakry, Guinea].

PMID- 18630055
TI  - [Genetic evolution of poliovirus: success and difficulties in the eradication of
      paralytic poliomyelitis].
AB  - Poliovirus, the aetiological agent of poliomyelitis, is an enterovirus of the
      Picronaviridae family. Despite the success of the World Health Organisation (WHO)
      worldwide vaccination campaign against poliomyelitis, poliovirus remains a public
      health problem in several developing countries, in Africa and Asia in particular.
      This is partly due to the considerable capacity of poliovirus strains to
      circulate and spread in populations with insufficient vaccine coverage. In
      addition, the attenuated strains of the oral polio vaccine (OPV) may rapidly
      evolve a neurovirulent phenotype, causing rare cases of paralytic poliomyelitis.
      The recent occurrence of epidemics associated with vaccine-derived poliovirus
      (VDPV) has highlighted the emergence of recombinant strains with genomes
      constituted of sequences from OPV strains together with sequences from non-polio
      enteroviruses. In this review, after briefly describing the molecular biology of
      poliovirus and the pathogenesis of poliomyelitis, we will provide an overview of
      the current situation concerning poliomyelitis prophylaxis and the strategies
      developed to fight this disease. We will also deal with the issue of the possible
      re-emergence of poliovirus after declaration of the eradication of wildtype
      poliovirus.

PMID- 18630057
TI  - [Family planning among women millet pounders in Dakar, Senegal].

PMID- 18630058
TI  - [The paradigm of diabetes].

PMID- 18630059
TI  - [Hypoglycemia and diabetes].
AB  - Hypoglycaemia represents the limiting factor to obtain good glycemic control.
      Dysregulation of counteracting mechanisms and autonomic nervous system neuropathy
      contribute a strong increase in the incidence of hypoglycaemia in type 1 diabetic
      patients, but also in long lasting type 2 diabetic patients. Hypoglycaemia in
      elderly poses a diagnostic and clinical challenge of the unsual clinical
      presentation causing a delay in treatment. Treatment however, is simple and
      follows early detection of symptoms by the patient and his family. Prevention has
      a major role and involves identification of individual risk factors for
      hypoglycaemia and patient's education with the objective of adapting treatment to
      the usual habits of the patient.

PMID- 18630060
TI  - [Importance of the post-prandial glycemia in the management of type 2 diabetes].
AB  - Cardiovascular disease is the main cause of mortality in diabetic patients. The
      risk of cardiovascular disease occurs at a lower glycemic level compared to
      microvascular complications. Post-prandial hyperglycemia seems to play a major
      role in the development of atherosclerotic lesions. In this article we review the
      evidence regarding the prognostic value of post-challenge hyperglycaemia relative
      to the risk of cardiovascular disease, explore the physio-pathologic mechanisms
      responsible for the negative effects of post-prandial hyperglycaemia and detail
      the benefits of treatment aimed at controlling post-prandial glycaemia.

PMID- 18630061
TI  - [Metabolic syndrome, a mitochondrial disease?].
AB  - The metabolic syndrome is a cluster of metabolic risk factors including:
      atherogenic dyslipidemia, elevated blood pressure, high plasma glucose and a
      prothrombotic and proinflammatory state, frequently associated to overweight.
      Impaired cell metabolism has been suggested as a relevant pathophysiological
      process. Indeed, the accumulation of intracellular fatty acylCoA and
      diacylglycerol, which then activate critical signal transduction pathways that
      ultimatly lead to suppression of insulin signalisation. Therefore a defect in
      mitochondrial function may be responsible for insulin resistance. Moreover,
      mitochondrial dysfunction has been found to take place in organs such as skeletal
      muscle, liver, pancreas and smoth vascular cells suggesting that mitochondrial
      defect could play a critical role in the occurence of cardiovascular diseases.

PMID- 18630062
TI  - [Metformin role in the treatment of type 2 diabetes in 2008].
AB  - Treatment of type 2 diabetes includes lifestyle adaptations and drug treatment
      with the recent availability of many new substances. Metformin is the best first
      option at present due to its efficacy, its neutral effect on weight, its security
      profile and its cost. In addition, metformin can be associated with any other
      antidiabetic agent. Sulfonylureas remain the best choice for combination with
      metformin although their effectiveness on glucose control decrease with time more
      rapidly compared with glitazones. The GLP-1 (glucagon-like peptide 1) analogues
      and DPP-4 (di-peptidyl-peptidase-4) inhibitors are effective but need long-term
      evaluation of their security profile. Insulin can be used when the different oral
      options have failed.

PMID- 18630063
TI  - [The inefficacy of glycemic control in the hospitalized patient: origins and
      solutions].
AB  - The hospital inpatient prevalence of diabetes mellitus can be estimated between
      20 and 30%. Even moderate hyperglycemia is associated with increased morbidity
      and mortality in the acute care setting, whereas efficient glycemic control has
      been shown to improve both of them significantly. Glycemic control however
      remains largely inefficient outside of the intensive care unit due to the
      persistance of an inadequate glycemic management practice. We are currently
      developing a clinical care project aimed at changing this practice. For an
      efficient glycemic control, a training programme for health care professionals
      based on the concept of covering the insulin needs of the patient is mandatory.
      This programme needs to be integrated in a systemic approach, which takes the
      professionals' context in account.

PMID- 18630064
TI  - [Patient education: the way for long-term follow up].
AB  - Therapeutic education is now perfectly integrated in caring and medicine. Its
      field of application is primarily in chronic diseases for the acquisition of
      competences in the management of treatments, in co-operation with health
      professionals. In ambulatory medicine, patients and health professionals are
      currently running up against the difficulties of the long-term follow-up with its
      part of uncertainty, lassitude and economic pressure. EBM and the various models
      of health psychology light us only partially the way. A new type of reflexive
      step is emerging. This way of thinking should place in its center the concept of
      therapeutic relation: between science and being. We summarize here our reflexive
      process in the course of an interdisciplinary team gathering social sciences, art
      and medicine.

PMID- 18630065
TI  - [Significant reduction in mortality and cardiovascular events in patients aged 80
      and over when treated with hypertensive agents].

PMID- 18630066
TI  - [Can we use patients' dreams in general medicine?].

PMID- 18630067
TI  - [Physicians and assisted suicide].

PMID- 18630068
TI  - [Is prostate cancer screening necessary?].

PMID- 18630069
TI  - [Questions surrounding Red Bull energy drink].

PMID- 18630070
TI  - [Autism and the maze of information].

PMID- 18630071
TI  - [Physician networks: what I think (14)].

PMID- 18630072
TI  - [Victory!].

PMID- 18630084
TI  - [New formulation of recombinant coagulation factor: simplicity, rapidity and
      manageability].

PMID- 18630085
TI  - [Hydroalcoholic products for handwashing in community nursing practice].

PMID- 18630086
TI  - [Quality of life and new management techniques for diabetic patients].

PMID- 18630087
TI  - [Nursing care theories 2/2. Divergent points of view].

PMID- 18630088
TI  - [Value of nursing care theories in community nursing practice].

PMID- 18630089
TI  - [Improving the quality of life in terminally ill patients, the value of the
      theory of Nancy Roper].

PMID- 18630090
TI  - [The "monthlies" of Pinel, or the necessity of thinking in psychiatric care].

PMID- 18630091
TI  - [Nursing practice in human becoming: the "Parse nurse" in French Switzerland].

PMID- 18630092
TI  - [The Academy of Nursing Sciences, multiple professional and social challenges].

PMID- 18630093
TI  - [4/10. Proteins].

PMID- 18630094
TI  - [4/11. The paraplegic patient].

PMID- 18630095
TI  - Reuse of needles in Nevada.

PMID- 18630096
TI  - An overview of current practice in hepatitis C testing.

PMID- 18630097
TI  - Polish up on past pestilence and present pathogens.
AB  - The cases presented here illustrate potential epidemic or pandemic events that
      once-silent pathogens portend. Developing countries, where defenses are limited,
      are primary targets. Of future concern are the developed countries that fail to
      use rigorous control measures established by the CDC, the WHO, and others to
      prevent the spread of infectious diseases. International travel has brought
      changes in demographics and a greater need for surveillance programs to control
      selective antibiotic resistance. In our first case, the patient's death would
      likely have been avoided if he had adhered to the CDC-recommended vaccine
      program. The fact remains that 20% to 60% of U.S. adults, including travelers to
      endemic areas, have not followed the diphtheria booster-vaccine schedule. Our
      second case demonstrates the ease of transmission through food and water that
      contribute to illness from cholera. The success of intravenous therapy or ORS
      treatment has reduced the number of deaths by approximately 3 million per year in
      Asia and Africa. Though development of oral vaccines may be promising, without
      water and sewage control, waterborne transmission of cholera is a continuing
      threat. The panic following our third case was a sample of the pandemonium an
      outbreak of XDR-TB would create. Lack of access to medical care and lack of
      funding in developing countries made selection of resistance from MDR- to XDR-TB
      a predictable event. The Global Plan to Stop TB 2006-2015, initiated to improve
      on the DOTS strategy to control TB/HIV and MDR-TB cases, targets 2015 for
      reducing overall prevalence and mortality from TB. Based on the principle that
      community healthcare is the best prevention, organizations that are dedicated to
      the control of emerging and re-emerging infection include the CDC, NIH, IDSA,
      ATS, and the National Academy of Science's Institute of Medicine, to mention a
      few. Recently, they have established plans and programs to address problems of
      communication among scientists and to improve surveillance in the detection and
      monitoring of dangerous pathogens. The remarkable and ever-changing dynamics of
      microbial adaptation, however, requires enormous vigilance and financial
      priorities worldwide. A coordinated effort by both scientists and public-health
      leaders is needed if the onslaught of infectious threats is to be controlled.

PMID- 18630098
TI  - Is your back-up power ready?

PMID- 18630099
TI  - Notes on disaster preparedness.

PMID- 18630100
TI  - Robin Martin nurses MST to success.

PMID- 18630101
TI  - Standard of care vs. state-of-the-art technology.

PMID- 18630102
TI  - OSHA inspections: avoid the big guns. A "culture of safety" is your best defense.

PMID- 18630103
TI  - Tune-up for trainers: help employees stay on top of their game.

PMID- 18630104
TI  - CMS reducing pay for HAC.

PMID- 18630105
TI  - World Health Organization global policy for improvement of oral health--World
      Health Assembly 2007.
AB  - The World Health Organization (WHO) Global Oral Health Programme has worked hard
      over the past five years to increase the awareness of oral health worldwide as an
      important component of general health and quality of life. Meanwhile, oral
      disease is still a major public health problem in high income countries and the
      burden of oral disease is growing in many low- and middle income countries. In
      the World Oral Health Report 2003, the WHO Global Oral Health Programme
      formulated the policies and the necessary actions for the improvement of oral
      health. The strategy is that oral disease prevention and the promotion of oral
      health needs to be integrated with chronic disease prevention and general health
      promotion as the risks to health are linked. The World Health Assembly (WHA) and
      the Executive Board (EB) are supreme governance bodies of WHO and for the first
      time in 25 years oral health was subject to discussion by those bodies in 2007.
      At the EB120 and WHA60, the Member States agreed on an action plan for oral
      health and integrated disease prevention, thereby confirming the approach of the
      Oral Health Programme. The policy forms the basis for future development or
      adjustment of oral health programmes at national level.

PMID- 18630106
TI  - Forensic dental investigations and age assessment of asylum seekers.
AB  - Age estimation is useful in forensic investigations to aid in the process of
      identifying unknown victims as well as living individuals. In many countries age
      estimation is commonly used to assist immigration authorities in deciding whether
      refugees or illegal migrants have reached that designated age that separates a
      juvenile from an adult. This is particularly important for the protection of
      unaccompanied minors. Italy is a country of great appeal for immigration as
      people from other Mediterranean countries can easily reach Italian coasts. In
      Italy, as in other western world countries, unaccompanied asylum seekers deemed
      to be under 18 face a very different path through the immigration system. They
      cannot be deported and are sent through a juvenile system where they have access
      to education programmes and may be granted a residence permit. The Section of
      Legal Medicine of the University of Bari was approached by Judges and Immigration
      Police with the question to assess the age of unaccompanied asylum seekers who
      claim to be below 18 years of age. The contribution of forensic odontologists for
      age estimation was recognised and since November 2006 age estimation of asylum
      seekers in Bari (Italy) relies on clinical and dental examination together with
      skeletal maturation as seen on radiographs of the left hand and wrist, the pelvis
      for iliac crests and root development and mineralisation of third molars as seen
      on an orthopantomogram.

PMID- 18630107
TI  - Influence of years of professional experience in relation to the diagnostic skill
      of general dental practitioners (GDPs) in identifying oral cancer and
      precancerous lesions.
AB  - OBJECTIVE: To evaluate skill in diagnosing cancer and oral precancerous lesions
      among general dentists in the Autonomous Community of Murcia (Spain). MATERIAL
      AND METHOD: Twenty randomly distributed clinical images were used, of which 45%
      corresponded to benign lesions, 35% to oral precancerous lesions, and 20% to oral
      cancer. Each case was accompanied by a summarised clinical history. The study
      sample comprised 150 general dentists divided into two groups: group I (60
      recently graduated dentists without professional experience) and group II (90
      dentists with established professional activity). RESULTS: In group I, the
      sensitivity of oral cancer diagnosis was 61.3% versus 85.5% in group II (p <
      0.001), while the sensitivity of precancerous lesion diagnosis was 71.7% in group
      I versus 80.7% in group II (p = 0.004). CONCLUSIONS: The results obtained show
      that junior dentists and general dentists with public or private practice need
      more training and more experience in diagnosing cancer and oral precancerous
      lesions.

PMID- 18630108
TI  - Dental caries and treatment needs in street children in Toluca, Mexico.
AB  - OBJECTIVE: To assess dental caries (deft and DMFT) and treatment needs, in street
      children from the city of Toluca in Mexico. METHODS: After informed consent from
      their parents, guardian or legal representative, 310 street children, 0 to 17
      years of age, from Toluca in the state of Mexico, were evaluated. Caries and
      treatment needs were recorded according to 1997 WHO criteria. The oral
      examination was carried out on site in daylight. RESULTS: For the population from
      which the sample was derived, the caries prevalence was 94.96%, the mean DMFT was
      6.0 +/- 4.6 (5.8 decayed), while deft was 3.5 +/- 3.7 (3.4 decayed). Treatment
      needs in the deciduous dentition revealed that 43.9% of teeth did not require any
      treatment, 20% needed fissure sealants, 19% required one surface restoration and
      13.19% needed restoration in two or more surfaces. In the permanent dentition,
      the treatment needs were as follows: 51.2% teeth did not need any treatment,
      22.9% needed fissure sealants, 18.4% required one surface restoration and 5.3%
      needed restoration in two or more surfaces. CONCLUSIONS: These findings
      illustrate the high prevalence of caries in street children in the city of
      Toluca. There is an enormous need for dental treatment; sealant applications were
      the treatment most in need. The data can serve as a platform to implement
      preventive and restorative dental health programmes that meet the needs of
      Mexican street children,

PMID- 18630109
TI  - Guidelines for occlusion strategy in implant-borne prostheses. A review.
AB  - Medium- or long-term failure of endosseous dental implants after
      osseointegration, when it has occurred, has been associated in the great majority
      of cases with occlusal overload. Overload depends ultimately on the number and
      location of occlusal contacts, which to a great extent are under the clinician's
      control. Much of our current understanding of occlusal contacts in this context
      is based on concepts derived from non-implant-borne prosthetics and has not been
      rigorously tested. The present article reviews occlussal contact designs and
      offers occlusion strategy guidelines for the main types of implant-borne
      prostheses.

PMID- 18630110
TI  - Comparison of the health condition between the 8020 achievers and the 8020 non
      achievers.
AB  - AIM: To review of the difference in the health condition between 8020 achievers
      and 8020 non-achievers covering 25 papers which were published mainly in Japan.
      BACKGROUND: A campaign targeting the elderly to retain at least 20 teeth by the
      time they reach the age of 80 years (8020) has been in place since 1991 in Japan.
      RESULTS: The percentage of 8020 achievers increased from 10.9% in 1993, 15.3% in
      1999 and 24.1% in 2005. The 8020 achievers had a tendency towards a strict
      upbringing and were not fond of sweets in their childhood. Physical indices such
      as height, weight, BMI score, bone mineral density, balance ability, grip
      strength, and exercise function in the 8020 achievers were better than the 8020
      non-achievers. A close inverse relationship between the number of teeth and heart
      rate was recognised. The food intake survey showed that 8020 achievers ate many
      kinds of food. However, these foods were those with less kilocalories and lower
      levels of carbohydrate. The 8020 achievers had good activity in daily life (ADL)
      level, were satisfied with life, and had a higher cumulative survival rate. Oral
      health conditions including periodontal condition, masticatory ability, occlusal
      force, occlusal and maxillofacial forms in the 8020 achievers were better than
      the 8020 non-achievers.

PMID- 18630111
TI  - Effect of Nd: YAG laser irradiation on the treatment of oral malodour associated
      with chronic periodontitis.
AB  - AIM: To investigate, using a randomised-controlled, single clinical trial whether
      treating periodontitis with non-surgical periodontal treatment procedures and
      laser applications can decrease the effect of oral malodour and compare the
      effectiveness of the different therapies. METHODS: Sixty patients suffering from
      chronic periodontitis and complaining of oral malodour were included in the
      study. The parameters measured included organoleptic scoring, volatile sulphur
      compound (VSC) levels, gingival index, plaque index, probing depth and clinical
      attachment levels before and after the different treatment procedures (oral
      hygiene instructions, scaling-root planing-SRP and subgingival Nd: YAG laser
      irradiation). RESULTS: There were significant relationships between oral malodour
      and the specific periodontal parameters. For all patients, there were
      statistically significant (p < 0.05) decreases in the clinical index scores and
      VSC values after all treatments. Although the VSC values decreased in all groups
      after treatment, laser treatment alone did not cause as large decreases as that
      achieved by SRP and SRP + laser irradiation. CONCLUSION: The results confirmed
      that in the population studied, oral malodour levels were significantly reduced
      after treating chronic periodontitis. The data indicated a possible adjunctive
      role for Nd: YAG lasers in periodontal therapy and treatment of oral malodour.

PMID- 18630112
TI  - Diurnal changes in oral malodour among dental-office workers.
AB  - PURPOSE: Dentistry is a major resource for the treatment of halitosis, therefore
      dental professionals must also pay attention to their own oral malodour for
      professional courtesy. However, oral malodour among dental professionals has not
      yet been investigated. In this study, the diurnal changes in oral malodour in
      dental-office workers were determined, and preventative measures were assessed.
      METHODS: Diurnal changes in the levels of volatile sulphur compounds (VSCs),
      which are the main cause of oral malodour, in mouth air were determined with a
      gas chromatograph specially designed for such analysis and the effects of several
      preventive measures were evaluated. RESULTS: High concentrations of VSCs in mouth
      air persisted during the morning and decreased after lunch. Tongue-cleaning
      followed by tooth brushing decreased VSCs dramatically. Further measures such as
      eating breakfast, drinking tea or using zinc mouthwash significantly decreased
      VSCs, but the effects were limited in dental hygienists who suffered from
      persistent oral malodour, especially in the afternoon. CONCLUSION: Eating
      breakfast, cleaning the tongue followed by brushing the teeth and zinc chloride
      mouthwash were very effective in preventing oral malodour in dental-office
      workers; however, the effectiveness of these preventive measures was limited in
      dental hygienists.

PMID- 18630113
TI  - [Pleiotropic effects of chitinase gene from Serratia plymuthica in transgenic
      potato].
AB  - We estimate the influence of transgenic bacterial chitinase from soilborne
      Serratia plymuthica onto agronomical important traits of potato, such as
      productivity and non-specific resistance. Transgene has been delivered into
      potato variety Delfin via Agrobacterial transformation with pGreen0229 and pBI121
      based vectors. Growth inhibition of chitin-containing pathogenic fungi was shown.
      However, over 40% oftransgenic lines demonstrated decreased non-specific
      resistance to late blight (down to 62% compared to control genotype), as well as
      40-60% productivity drop.

PMID- 18630114
TI  - [Construction and characterization of immune combinatorial cDNA library of mouse
      variable immunoglobuline genes].
AB  - A cDNA combinatorial antibody library of mouse variable immunoglobulin fragments
      has been constructed from mice immunized with rhIFN-beta1b. For this purpose,
      cDNAS of immunoglobulin variable heavy (V(H)) and variable light (V(L)) chains
      genes amplified from splenocytes were joined with linker DNA to form ScFv's
      (single-chain Fv-antibodies). The obtained ScFv-DNA pool was cloned into a
      phagemid vector and used for Esherichia coli transformation. Using the phage
      display technique, bacterial clones producing single-chain antibodies specific to
      rhIFN-beta1b were selected. The following characteristics of the combinatorial
      library were determined in this work: abundance, functional size, and the initial
      ScFv-DNA diversity in the library constructed. High specificity of interaction
      between phage displayed ScFv's and rhIFN-beta1b has been demonstrated.

PMID- 18630115
TI  - Purification of recombinant GFP produced by Agrobacterum-mediated transient
      expression in Nicotiana excelsior.
AB  - Green fluorescent protein (GFP) is commonly used as a reporter protein in a wide
      range of biological experiments. The efficient protocol of Agrobacterium-mediated
      transient expression in Nicotiana excelsior was applied for quick preparative
      production of recombinant GFP. The protein purification scheme has been developed
      and included ammonium sulfate precipitation and Q-sepharose anion-exchange
      chromatography. It results in obtaining of a fraction with about 85% GFP
      homogeneity and the protein yield of about 75%.

PMID- 18630116
TI  - [Callose accumulation during treatment of tomato (Lycopersicon esculentum L.)
      cells with biotic elicitors].
AB  - Time-course of induced accumulation of callose in tomato cells has been studied.
      Localization of callose in L. esculenthum cells was investigated by fluorescent
      microscopy technique, and the optimal time for its determination was found.
      Callose accumulation in tomato cells treated with different biotic elicitors was
      determined. Nonlinear dependence between callose accumulation and concentration
      of chitin oligomers (with 3-5 N-acetylglucosamine fragments) was established.
      Increasing of callose accumulation in tomato cells was proportional to the
      increase of concentration ofchitin dimer and chitosan in the culture medium.

PMID- 18630117
TI  - [Effect of norfloxacin on ultrastructure characteristics of the loach embryos].
AB  - The ultrastructure of embryo cells of the loach (Misgurnus fossilis L.) at the
      stage of the first and the tenth blastomer divisions in the control and under the
      conditions of fluoroquinolone norfloxacin (5 and 25 mkg/ml) influences has been
      investigated. The effect of this antibiotic has resulted in significant
      ultrastructural changes of embryo cells, such as hypertrophy of channels of the
      smooth and rough endoplasmic reticulum, disorganization of mitochondrias and
      cytoplasm membrane destructions of embryo. It has been established that
      fluoroquinolone inhibited biosynthetic processes, directly influencing on the
      blastomer biosynthetic structures. Such results testify a high norfloxacin
      embryotoxicity.

PMID- 18630118
TI  - [Dynamics of genome changes in Rauwolfia serpentina callus tissue upon the switch
      to conditions of submerged cultivation].
AB  - Genome of Rauwolfia serpentina callus cells was found to fail undergo the
      noticeable changes for several early passages upon the switch from surface to
      submerged cultivation in the liquid medium of special composition. After
      subsequent 4-6 passages in submerged culture RAPD spectra polymorphism was
      revealed which may reflect the changes in DNA sequence as well as in the
      structure of cell population that forms the strain. Introduction of the
      intermediary passage on the agar-solidified medium of more simple composition
      prior to transfer into liquid medium appeared not to affect essentially the level
      and the pattern of genome changes.

PMID- 18630119
TI  - [Effect of reparation processes on formation of human individual radiosensitivity
      at the chromosome level].
AB  - The results of experimental investigations of the role of DNA repair as the key
      factor of human individual radiosensitivity formation are presented. It is shown
      that repair potential of hypersensitive to irradiation individuals is
      approximately twice lower as compared with the control group.

PMID- 18630120
TI  - [Y-chromosome microdeletions as a prognostic marker of male infertility].
AB  - The results of molecular-genetic study of Y-chromosome microdeletions in men with
      spermatogenesis failure and in patients with cryptorchism are presented. The
      molecular-genetic studies of regions AZFa, AZFb, AZFc in STS loci - sY84, sY86,
      sY127, sY134, sY254, sY255 and SRY gene have been performed. Y-chromosome
      microdeletions were detected in 13,3% infertile men with spermogram failure. The
      frequency of genetic (cyto- and molecular) abnormalities among boys with isolated
      cryptorchism was 4%. The results show the necessity of additional study ofgenetic
      factors ofcryptorchism development.

PMID- 18630121
TI  - [Population and molecular-genetic aspects of hemophilia A and B in Uzbekistan].
AB  - This work summarizes the results of conducted retrospective epidemiologic and
      molecular genetic investigations of Hemophilia A and B in Uzbekistan. Totally
      1304 Hemophilia A and B cases were registered in the republic during the period
      from 1991 to 2004. Morbidity rate varied from 0.75 up to 1.46 per 10,000 new born
      boys. An average birth rate of patients with Hemophilia A and B for 10 years
      period (1991-2000) was 1:8735 (1.14 x 10(-4)) of born boys. Some peculiarities of
      DNA polymorphism in genes of blood coagulation factors VIII and IX in Uzbek
      population have been analyzed. Frequency of alleles was studied and self
      descriptiveness of these gene markers for revelation of heterozygous carrier and
      prenatal diagnostics of hemophilia A and B have been determined. Finally DNA
      diagnostics of Hemophilia A and B were summed up.

PMID- 18630122
TI  - Application of multiplex PCR with histopathologic features for detection of
      familial breast cancer in formalin-fixed, paraffin-embedded histologic specimens.
AB  - Breast cancer is the most common malignancy among females in the world. Age and
      familial history are the major risk factors for the development of this disease
      in Iran. Mutations of BRCA1 and BRCA2 genes are associated with a greatly
      increased risk for development of familial breast cancer. Frequency of BRCA
      mutations was identified in familial breast cancers (FBC) and non-familial breast
      cancers (NFBC) by molecular genetics, morphological and Immunohistochemical
      methods. Thirty forth formalin-fixed, paraffin-embedded breast tissue tumors were
      analyzed from 16 patients with FBC and 18 patients with NFBC. Three 5382insC
      mutations detected by multiplex PCR in 16 familial breast cancers.
      Immunohistochemical method was used to detect estrogen receptor (ER) and
      progesterona receptor (PR) and TP53. Comparison of ER, PR and TP53 exhibited high
      difference (P < 0.0001) in familial breast cancers and non-familial breast
      cancers. Our results demonstrated that 5382insC mutation, ER, PR, TP53, mitotic
      activity, polymorphism, necrosis and tubules can serve as the major risk factors
      for the development of FBC.

PMID- 18630123
TI  - [Molecular-genetic analysis of natural and stimulated ovulation impairment].
AB  - The influence of FMR1, INHalpha1, NAT2, GSTT1 and GSTM1 genes on ovarian
      function, and their association with POF and "poor response" to exogenous GT
      after ovulation stimulation were investigated. The carriers of Ala257Thr
      transition predominated in the studied "poor responders" group. This transition
      combined with intermediate alleles of FMR1 gene was observed in 1.6% POF patients
      and 2.5% persons from "poor responders" group but in nobody of the control group.
      The frequency of deletion in GSTM1 gene in "poor responders" group was
      significantly higher (p = 0,01) than in normal ovulatory control group. The
      frequency of Ser680Ser-Ala307Ala polymorphic genotype (22.2%) in "poor
      responders" group was significantly higher (p = 0.028) than in normal-ovulatory
      control group (7.7%). The daily dosage of GT in intermediate alleles of FMR1 gene
      carriers as well in patients with "slow acetylation" NAT2 genotype was
      significantly higher in comparison to patients without intermediate alleles and
      patients with "quick acetylation" NAT2 genotype. Quantity of oocytes after
      ovulation stimulation in women with INHa1 gene Ala257Thr transition was
      significantly decreased in comparison to patients without such mutation. Further
      investigations of these genes can play a major role in POF studying and
      modulation of ovarian response to exogenous GT.

PMID- 18630124
TI  - [Metabolic engineering of the initial stages of xylose catabolism in yeasts for
      construction of efficient producers of ethanol from lignocelluloses].
AB  - Plant biomass possesses a huge potential as a source for biofuel production. The
      main components of biomass are glucose and five-carbon sugar xylose. The yeast
      Saccharomyces cerevisiae that is used for industrial ethanol production from
      glucose is unable to xylose fermentation. Therefore a microorganism capable for
      efficient fermentation of both glucose and xylose has to be found in nature or
      constructed for economically feasible biomass conversion to ethanol. The active
      xylose fermentation could be performed by increasing the efficiency of initial
      stages of xylose metabolism. In this review the enzymes of initial stages of
      xylose metabolism in yeasts (xylose reductase, xylitol dehydrogenase,
      xylulokinase) and bacteria (xylose isomerase and xylulokinase) are characterized.
      The ways for construction of yeast strains capable of efficient alcoholic xylose
      fermentation are discussed.

PMID- 18630125
TI  - [Health care related infections caused by multiresistant microorganisms--how to
      beat them].

PMID- 18630126
TI  - [External fixation in the treatment of open tibial shaft fractures].
AB  - BACKGROUND/AIM: Besides the conquasant fractures, open tibia shaft fractures
      belong to the group of the most severe fractures of tibia. Open tibia shaft
      fracture is one of the most common open fractures of long bones. They most
      frequently occur as a result of traffic accidents caused by the influence of a
      strong direct force. METHODS: Within the period from January, 2000 to December
      31, 2005 at the Clinic for Orthopaedics and Traumatology, Clinical Center Nis,
      107 patients with open tibial fractures were treated. We analyzed 96 patients
      with open tibial fracture. In the series analyzed, the male sex was prevalent-
      there were 74 men (77.08%). The mean age was 47.3 years. The youngest patient was
      17 years old, while the oldest patient was 79. According to the classification of
      the Gustilo et al. in the analysed group there were 30 (31.25%) open tibial
      fractures of the I degree, 31 (32.29%) of the II degree, 25 (26.05%) of the III A
      degree, 8 (8.33%) of the III B degree and 2 (2.08%) of the III C degree. In 95 of
      the patients the treatment of open tibia shaft fractures consisted of the
      surgical treatment of wound and the external fixation of the fractured bone using
      "Mitkovic" type external fixator with a convergent method of pin applications.
      One primary amputations had been done in patients with grade IIIC open tibial
      fracture with large soft tissue defect. RESULTS: Of the 96 open tibial fractures
      available for follow-up, 73 (76.04%) healed without severe complications
      (osteitis, pseudoarthrosis, valgus malunion and amputation). There were nine
      (9.38%) soft tissue pin track infections and six (6.25%) superficial wound
      infections. The mean time of union was 21 (14-36) week. Among severe local
      complications associated with open tibial fractures, in eight patients (8.33%)
      was registered osteitis, and in nine patients (9.38%) fracture nonunion and the
      development of pseudoarthrosis. Three of the patients (3.13%) had more than 10
      degree valgus malunion. In one patients (1.04%) deep pin track infection
      developed. Two patients (2.08%) had below the knee amputation (one primary in
      patient with type III C open fracture and one secondary after the development of
      deep infections). CONCLUSION: Surgical treatment of wounds, external fixation,
      leaving the wounds open and performing necessary debridements, adequate drug
      therapy administration are essential for obtaining good results in patients with
      open tibial shaft fractures.

PMID- 18630127
TI  - [Prevalence and characteristics of endometrial polyps in patients with abnormal
      uterine bleeding].
AB  - BACKGROUND/AIM: The prevalence of endometrial polyps (EPs) in the general female
      population is about 24%. Abnormal uterine bleeding is frequently the presenting
      symptom of EPs. The aim of this study was to determine the prevalence and
      characteristics of EPs in patients with abnormal uterine bleeding. METHODS: The
      prevalence and characteristics of EPs were investigated in 961 patients with
      abnormal uterine bleeding who underwent dilatation and curettage between January
      and December 2006. Regarding histopathological features of EPs (presence of
      atypical hyperplasia or endometrial carcinoma), patients were divided into two
      groups: group A--patients who had EPs and EPs with hyperplasia without atypia (n
      = 204) and group B--patients who had EPs with atypical hyperplasia and EPs with
      carcinoma (n = 7). RESULTS: In 211 (21.94%) patients EPs were found with abnormal
      uterine bleeding. Histopathologically, there were 175 (82.94%) EPs, 29 (13.74%)
      EPs with hyperplasia without atypia, 5 (2.37%) EPs with atypical hyperplasia, and
      2 (0.95%) EPs with endometrial carcinoma. Contrary to the patients with EPs and
      EPs with hyperplasia without atypia (group A), patients who had EPs with atypical
      hyperplasia and EPs with carcinoma (group B) were older (p < 0.05), and more
      commonly postmenopausal (p < 0.05) and with hypertension (p < 0.05), all of
      statistical significance. CONCLUSION: The prevalence of endometrial polyps in
      patients with abnormal uterine bleeding according to our data was 21.95%.
      Atypical hyperplasia and endometrial carcinoma were rarely confined to a polyp.
      Older age, postmenopausal period and hypertension may increase the risk of
      premalignant and malignant changes in endometrial polyps.

PMID- 18630128
TI  - [Correlation between 24-hour profile of blood pressure and ventricular
      arrhythmias and their prognostic significance in patients with arterial
      hypertension].
AB  - BACKGROUND/AIM: Left ventricular hypertrophy (LVH), apart from arterial
      hypertension, is a risk factor for electrophysiologic heart condition disorder
      and sudden cardiac death. The aim of this study was to examine a relationship
      between complex ventricular arrhythmias and parameters of 24-hour ambulatory
      blood pressure monitoring in the patients with arterial hypertension and left
      ventricular hypertrophy (LVH), as well as their prognostic significance during a
      five-year follow-up. METHODS: Ninety patients with arterial hypertension and LVH
      were included in this study (mean age 55.2 +/- 8.3 years). There were 35 healthy
      people in the control group (mean age 54.5 +/- 7.1 years). Left ventricular mass
      index was 171.9 +/- 32.4 g/m2 in the LVH group and 102.4 +/- 13.3 g/m2 in the
      control group. Clinical examination, echocardiogram, 24-hour ambulatory blood
      pressure monitoring and 24-hour holter monitoring were done in all of the
      examined persons. Ventricular arrhythmias were classified by the Lown
      classification. RESULTS: In the LVH group there were 54 (60.0%) of the patients
      with > or = III Lown class. The best predictor of a Lown class were left
      ventricular mass index by using multivariate stepwise regression analyses (beta =
      0.212; p < 0.05) and small decrease of diastolic blood pressure during the night
      (beta = -0.293; p < 0.01). The main predictor of bad prognosis was left
      ventricular mass index during a five year follow-up (beta = 0.302; p < 0.01, for
      stepwise regression model: F = 8.828; p < 0.01, adjusted R2 = 0.091). CONCLUSION:
      Left ventricular arrhythmias are frequent in patients with lower decrease of
      blood pressure during the night. There was no correlation between the degree of
      ventricular arrhythmias and parameters from 24-hour blood pressure monitoring and
      a five-year prognosis in the patients with arterial hypertension and LVH. A bad
      five-year follow-up outcome of hypertensive disease depends on left ventricular
      mass index.

PMID- 18630129
TI  - [Early results of liver resection due to metastases of colorectal carcinoma].
AB  - BACKGROUND/AIM: Liver metastases are most frequently the result of colorectal
      carcinoma. The aim of this study was to analyse early results of operative
      treatment of the patients with the liver metastases of colorectal carcinoma.
      METHODS: This retrospective, prospective study included 387 patients with
      colorectal carcinoma operated during the period from 2005-2007. All the patients
      were submitted to oncologic surgery protocol. The functional state of the liver
      was assessed, especially in the patients with hemotherapy. Diagnostic protocol
      further included color Doppler ultrasonography of the liver and port system, as
      well as spiral computed tomography includy angiography. Nine (5.7%) of the
      patients were submitted to explorative laparotomy. RESULTS: Of all the patients
      157 (40.6%) had metastases in the liver, synhronous 78 (20.15%) and metachronous
      79 (20.45%), Forty two (26.7%) patients were indicated for the liver resection.
      In 33 (21%) of them it was performed successfully. There were 18 females and 15
      males of the average age 60.09 (42-81) years. Up to 4 metastases had 90.9% of the
      patients and in 9.09% had up to 5 and more metastases. On average, metastases
      occupied 2.6 of the liver segments. There were 21.2% of solitary lesions (7
      patients), 63.6% of multilple unilobular (21 patients) and 15.15% of multiple
      bilobular metastases (5 patients). Liver resection was done using ultraharmonic
      scalpel. At spacious liver resections we used a device for intraoperative saving
      of blood (cell saver) and applied a technique of selective hepatic vascular
      exclusion. An average disease-free interval was 16.7 months. There were 60.6% of
      anatomical liver resections and 39.4% of atypical resections. In 31.1% of the
      operated patients we made resection on up to two segments of the liver and in
      30.3% we made resection of four segments. An average number of segments where
      resection had been performed was 2.65 and the duration of operation was 143
      minutes. In 39.4% of the cases we used a technique of liver vascular isolation,
      an average duration was 38 minutes. In 30.3% of resections we used cell saver and
      70% of operated patients were transfused. On average, 493 ml of blood was
      transfused. Of the total number of resections, 90.9% was of the type R0, 9.09% of
      the type R1. An average duration of postoperative hospitalization was 10.6 days.
      Operative morbidity rate was 15.15% and operative mortality 3.03%. During a six
      month observing there were not any mortality or repeated metastases in liver.
      CONCLUSION: Anatomic liver resection including selective vascular hepatic
      excision by the use of an ultraharmonic scalpel and cell saver is considered to
      be efficient and secure method for the reduction of intraoperative and
      postoperative complications rendering good surgical results.

PMID- 18630130
TI  - [Effect of recasting on the thickness of metal-ceramic interface of nickel
      chromium and cobalt-chromium alloys].
AB  - INTRODUCTION/AIM: This research was done to establish recasting effects of nickel
      chromium and cobalt-chromium alloys on the thickness of their metal-ceramic
      interface in making fixed partial dentures. Metal-ceramic interface determines
      their functional integrity and prevents damages on ceramics during mastication.
      Investigation of metal-ceramic samples is supposed to show if base metal alloys
      for metal-ceramics are successfully recycled without any risk of reduction of
      metal-ceramic interface thickness. METHODS: The research was performed as an
      experimental study. Per six metal-ceramic samples of nickel-chromium alloy
      (Wiron99) and cobalt-chromium alloy (Wirobond C) were made each. Alloy residues
      were recycled through twelve casting generations with the addition of 50% of new
      alloy on the occasion of every recasting. Analysis Energy Dispersive X-ray (EDX)
      (Oxford Instruments) and Scanning Electon Microscop (SEM) analysis (JEOL) were
      used to determine thickness of metal-ceramic interface together with PC Software
      for quantification of visual informations (KVI POPOVAC). RESULTS: Results of this
      research introduced significant differences between thickness of metal-ceramic
      interface in every examined recycle generation. Recasting had negative effect on
      thickness of metal-ceramic interface of the examined alloys. This research showed
      almost linear reduction of elastic modulus up to the 12th generation of
      recycling. CONCLUSION: Recasting of nickel-chromium and cobalt-chromium alloys is
      not recommended because of reduced thickness of metal-ceramic interface of these
      alloys. Instead of recycling, the alloy residues should be returned to the
      manufacturers.

PMID- 18630131
TI  - [Age as a risk factor for suicide].
AB  - BACKGROUND/AIM: World Health Organization (WHO) in its plan for health policy
      until the year 2010, has taken reduction of risk factors of suicide as its 12th
      aim. Because of the fact that the problem of suicide is also significant health
      problem in our society, the aim of this study was to examine the influence of
      life period as a risk factor for suicide in the area of the town of Kragujevac.
      METHODS: In total 211 persons, both sexes, aged between 17 and 91 years, from the
      area of the town of Kragujevac, who had been committed a suicide during the
      period from 1996 to 2005, were included in a retrospective study. This study
      included the analysis of: conditions prior to suicide, locations of suicide,
      motives for suicide, the ways of committing suicide. For statistical analysis
      chi2 test and univariante regression model were used. RESULTS: Average rate of
      suicide, in analyzed period, moved from 8.7 to 27 with a mean value of 14.6 +/-
      6.9. Suicide rates were the lowest in the age group from 15 to 24 years and the
      highest in the age group above 65 years (p < 0.05). Among the presuicidal
      conditions, within any age groups the presence of mental disease dominated as a
      factor for suicide, but within the oldest one in which organic diseases prevailed
      as a factor for suicide (p < 0.05). Statistically significant fact is that a
      house (flat) was the main location for commiting suicide in any age groups.
      Motives for suicide were significantly different within the groups and they were
      mostly unknown. Committing suicide by hanging was the most frequent way of
      suicide among any age groups. Univariant regression analysis faild to show any
      impact of age on the analyzed factors. CONCLUSION: Because of the fact that an
      average rate of suicide in elderly increases it is obligatory to primarily
      determine risk factors for suicide among people more than 65 years of age.
      Physicians should play the most important role in that.

PMID- 18630132
TI  - [Staphylococcus aureus methicillin-resistance mechanisms].
AB  - BACKGROUND/AIM: In many hospitals in the world and in our country, the spread of
      methicillin-resistant Staphylococcus aureus (MRSA) is so wide that nowdays
      vancomycin is recommended for empiric treatment of staphylococcal life
      threatening infections (sepsis, pneumonia) instead of beta-lactam antibiotics.
      The aim of this study was to determine the production of beta-lactamases in
      hospital and community isolates of staphyloococus aureus, i.e. hospital
      associated MRSA (HA-MRSA) and community associated MRSA (CA-MRSA), the presence
      of homogeneous and heterogeneous type of methicillin resistance, and border-line
      resistance in Staphylococcus aureus (BORSA). The aim of this study was also to
      determine if there was a statistically significant difference between mechanisms
      of resistance in HA-MRSA and CA-MRSA. METHODS: A total 216 clinical
      Staphylococcus aureus isolates from the General Hospital in the town of Cuprija
      and 186 ambulance Staphylococcus aureus isolates from the community were examined
      for the presence of methicillin-resistance using disk-diffusion test with
      penicillin disk (10 ij), oxacillin disk (1 microg) and cefoxitin disk (30
      microg). Beta-lactamases production was detected by nitrocefin disk and beta
      lactamase tablets. Determination of oxacillin minimum inhibitory concentracion
      (MIC) was done by agar-dilution method. RESULTS: The prevalence of HA-MRSA was
      57.4%, and CA-MRSA was 17.7% (p < 0.05). There was a higher rate of heterogeneous
      type of resistance among clinical MRSA isolates (11.1%) compared with ambulance
      ones (3.8%) (p < 0.05). The rates of beta-lactamases production were similar
      among hospital associated isolates (97.5%), as well as in the community
      associated isolates (95.5%) (p > 0.05). There were 4.6% of BORSA hospital
      isolates and 3.3% of BORSA ambulance isolates (p > 0.05). CONCLUSION: The
      frequency of MRSA isolates in hospital was significantly higher than in
      community, as well as the heterogeneous type of resistance. The frequency of
      BORSA isolates and production of beta-lactamases were higher among hospital
      Staphylococcus aureus isolates, but the difference is not significant.

PMID- 18630133
TI  - [Evaluation of schizophrenic patients quality of life].

PMID- 18630134
TI  - [Hypocretin neurotransmitter system and narcolepsy].

PMID- 18630135
TI  - Mandibular reconstruction--state of the art and perspectives.

PMID- 18630136
TI  - An autopsy case of asthmatic death--usefulness of biochemical examination.
AB  - BACKGROUND: Asthma is the one of the major causes of sudden death in Japan.
      Postmortem diagnosis of asthma has been based on morphological findings in lungs,
      but it histological evidence, was also reported that the biochemical markers such
      as total and specific immunoglobulin E (IgE) are useful. CASE REPORT: We present
      here a case of fatal asthmatic death. A Japanese male in his thirties,
      complaining of dyspnea, collapsed suddenly. He was taken by ambulance to
      hospital, but cardiopulmonary resuscitation was ineffective. From autopsy
      findings, we concluded that the cause of death was asphyxia due to asthma attack.
      Biochemical findings indicated that the deceased had a severe asthmatic
      condition. CONCLUSION: In the presented case, the biochemical examination of the
      serum obtained at autopsy gave helpful information for the diagnosis that
      asthmatic attack was a cause of death.

PMID- 18630137
TI  - Ectopic mammary tissue in vulva.
AB  - BACKGROUND: Ectopic mammary gland tissue is a residual tissue that persists
      during the embryologic development along ectodermal primitive milk streaks.
      Incomplete involution anywhere along the primitive milk streak can result in
      accessory or ectopic mammary tissue. CASE REPORT: A woman, 27-year old, admitted
      to Obstetrics and Gynecology Clinic Kragujevac for surgery, of goose-egg size,
      vulva tumor, of elastic consistency. Menarche started in 12 years of age, with
      the regular menstrual cycle, without previous gyneocological diseases. The woman
      had one pregnancy terminated by cesarean section because of the multiple (twin)
      pregnancy. Excision of the tumor was completely done in the total endotracheal
      anesthesia. Pathohistologic (PH) findings was: Dysplasia fibrosa cystica simplex
      mammae, with focuses of sclerosing adenosis. Expression of estrogen (ER) and
      progesterone receptors (PR) were positive. CONCLUSION: Ectopic mammary tissue in
      vulva in adult period is very rarely seen, and can be changed pathologically as
      well as normally positioned breast tissue into benign cystic changes, benign
      tumors, adenomas and fibroadenomas and tumors. Cells with low ER/PR receptor
      level grow independently of estrogene stimulation and they could be resistant to
      hormonal therapy effects.

PMID- 18630138
TI  - [Chronobiology and practical medicine].
AB  - In present time, to classify the healthy as potencional possibility of the
      organism to accept variable environment influences without the break of the
      biological important functions is not satisfactory. Examples from the different
      field of the clinical medicine refer to importance of the knowledge's of the
      circadian rhythmicity concerning many diseases, symptoms or significant
      remissions. Therefore, clinical trials considering the biological variability
      differ from the convectional studies by assumption that biology of patient is
      dynamic, that time of the diagnostic test running is significant and that drugs
      can influence safety and therapeutic effect in the dependence on the day-time. In
      paper, it is showed on some examples from the clinical practice that respection
      of the chronobiological principles may play the important role in the medical
      diagnostics as well as in therapy and may improve accuracy of the whatever
      functional examination. For terms, which are often used in the chronobiological
      texts, no suitable terms were available and therefore it was necessary to
      introduce the descriptive phrases, which would be accepted by specialists in the
      field. Many of the introduced terms are still unknown to many investigators and
      physicians who might benefit from the application of chronobiologic principles to
      their work.

PMID- 18630139
TI  - Short review of some properties of muscular proteins.
AB  - Proteins are the basic material of tissue structure. They are the most important
      component of striated skeletal muscle. Their classification is correlated with
      the histological structure of muscle tissue. The muscle proteins can be divided
      in to contratile, regulatory, sarcoplasmic and extracellular forms. The most
      important are the contractile proteins actin and myosin. Among the regulatory
      proteins, troponin, tropomyosin, M-protein, beta-actin, gamma-actin and C-protein
      are great importance. Sarcolemma is also a protein component. Proteins such as
      myoglobin, myogen, myoalbumin and x-globulin are found in the sarcoplasm and
      proteins such as elastin, collagen and reticulin are also found in the muscle.
      The remaining of proteins includes myofibrillar proteins of the Z-disc as well as
      small quantities of other proteins. This work is a short review of some
      properties of the muscular proteins.

PMID- 18630140
TI  - [Methamphetamine--a drug of pregnant female drug addicts].
AB  - Drug abuse is still a serious problem of nowadays. One of the most abused drugs
      in the Czech Republic is methamphetamine (MA). MA is strongly addictive substance
      with high disposition to abuse. It belongs to the group of synthetic amphetamines
      that together with cocaine and caffeine are classified as psychomotor stimulant
      drugs. Lately, the growing problem is drug abuse of pregnant women. MA is popular
      drug in pregnant women dependent on addictive substances. Drugs abused during
      pregnancy are risky not only for the mother, but may induce changes in developing
      organism that may have permanent consequences. Prenatal exposure to MA may have
      teratogenic effects by inducing malformations or impair postnatal functional
      development of offspring. The impairing effects may last until adulthood and may
      affect even next generation. Mechanism of these long-term consequences is not
      fully explained yet. The present review summarizes the existing information.

PMID- 18630141
TI  - [Antioxidants and their gastrointestinal absorption and interferences of their
      effects].
AB  - Antioxidants and trace elements are using by hundreds millions of people.
      Effective are especially mixtures of antioxidants. Usually is declared only the
      composition of the tablets, but nowadays it is not satisfactory. Substantial is
      how much of the antioxidants is absorbed and where, how it increases the
      antioxidant capacity in the blood, which effect it has, the stability of them and
      who, how much, which and when they are to be used. It is also very important
      which antioxidants during the detoxication of free radicals react first and
      therefore they are soon exhausted and whether at all or how quickly can they be
      reduced back to an active component. In aging the antioxidant capacity decreases,
      it is influenced by the season, all of factors are to be taken in account. The
      absorption and the effect are influenced by the state of gastrointestinal tract,
      including the microbiological flora, pH, the size of the molecules, sometimes by
      partial oxygen tension in the blood. Free radicals are generated mostly after a
      load and therefore it is suitable to have the antioxidants capacity on a high
      level, it is possible to increase it during the load and it is recommended the
      administration of them after the load. Some authors recommend low doses of
      antioxidants five times a day. In some diseases the antioxidants are effluenced
      from the tissues to the blood and then there is a defficit in tissues of them.
      Important are the interferences during the absorption, their metabolism in
      organism; it may decrease their level or increase their effectivness, the
      metabolism can infuence to which tissues are the antioxidants deposited, and how
      long will stay the increased level of antioxidant capacity. The speed of
      elimination by urine and stool is also important. It is useful to know from which
      and how much of isomers the antioxidant is composed, because the single isomer
      may have a different effect. The origin of antioxidants is important, as natural
      antioxidants are usually more effective than the sythetic ones. The toxicity of
      the substances should not to be neglected. Storing of antioxidants sometimes
      deteriorate them, or sometimes they are contaminated by anabolic steroids. Some
      substances like phytates can bind them and so decrease their bioavavilability.
      Lipid soluble substances need lipids in the diet, some antioxidants are
      differently absorbed from different sources of nutrition. Genetic equipment is
      important as well. It is apparent that the administration of antioxidants and
      trace elements is not simple and that the informations of commercial preparates
      is usually not sufficient, probably in the future at least may be mentioned total
      antioxidant capacity.

PMID- 18630142
TI  - [Adolescent medicine: advocates of a global approach for public health problems].

PMID- 18630143
TI  - [Food habits and body image of students in Lausanne].
AB  - During adolescence, nutrition needs are high; however the literature shows that
      few adolescents are following standardized nutritional requirements. A few weeks
      before an intervention about nutrition to high school adolescents in Lausanne,
      they were invited to fill in a self-reported questionnaire about their nutrition
      modes and habits, and their self-image satisfaction (N = 198). Results show that
      only 5% of youth are eating 5 fruits and vegetables per day and only 29% 3 to 5
      dairy products. 21% of female and 6% of boys are not satisfied about their self
      image, and those exhibiting a poor self-image tend to adopt health compromising
      eating patterns in a higher proportion. During adolescence it is important not
      only to investigate the nutritional habits but also one's self image.

PMID- 18630145
TI  - [The transition from pediatric to adult care of chronically ill adolescents].
AB  - The transition from pediatric to adult care of chronically ill adolescents Even
      though the transition from pediatric to adult health care is extremely important
      for chronically ill adolescents, most of the times it is limited to a simple
      transfer The objective of this paper is to describe the barriers to a smooth
      transition from the point of view of the patient and his/her family, the health
      professionals and the health system, to review the key elements for a smooth
      transition, and to address the different approaches proposed in the literature.

PMID- 18630144
TI  - [What role may general practitioners play in the treatment of adolescents
      suffering from psychotropic substance use and misuse?].
AB  - Substance use and misuse are well-known public health issues. Indeed, more than
      half of the adolescents involved with substances has seen a general practitioner
      at least once in a recent period. Early identification of substance use and
      misuse among teenagers is a major issue, in which general practitioners could
      play a larger role. The DEPART program, based in the canton of Vaud, offers
      specific support to help general practitioners identify substance use and misuse
      early on and, when necessary, provide specific care in the form of motivational
      interviewing.

PMID- 18630146
TI  - [Female genital mutilation--need for answers at the age of adolescence].
AB  - In Switzerland, the estimated number of survivors after traditional female
      genital mutilation in the country of origin or girls and adult women at risk is 6
      7000. Health professionals must be able to respond adequately to their questions
      not only during adolescence but through out the different periods of life. The
      lack of information or transmission by the seniors as well before the excision as
      at the time of sexual maturity contributes in a large measure to the frequent
      biographic trauma. It can be very difficult for the girls to deal with the gap
      between socio cultural and family expectations and their individual life
      experience in Switzerland.

PMID- 18630147
TI  - [Risk-taking in adolescence. Screening and counseling strategies for primary care
      professionals].
AB  - Meeting adolescents' health needs in primary care implies knowledge of
      developmental, psycho-social and physical specificities of this age group.
      Primary care physicians need appropriate communication skills and knowledge of
      specific adolescent health issues such as the role of families, the need for
      confidential services and networking with schools, social services and other key
      individuals in young people's lives. Primary care physicians rarely receive
      training in adolescent health and are usually interested in practical screening
      or counselling strategies. HEADSSS is a useful mnemonic to guide the psychosocial
      interview of an adolescent. It can be used in daily practice to help the
      physician to focus not only on "risk taking", but also on the personal strengths
      and protective factors that allow young people to develop harmoniously.

PMID- 18630148
TI  - [Consultations for adolescents: which setting?].
AB  - Consultations with adolescents have their specificities, there is a triangular
      situation between the adolescent patient, his parents and the physician. The
      setting of the consultation has to take into consideration the developmental
      stages of adolescence for to give an appropriate response to the expectations and
      needs of the patient and his parents. Questions about confidentiality are
      fundamental and has to be openly discussed. The condition for medical
      confidentiality for an adolescent is his capacity for exercising autonomous
      choices; on the other hand the parents have the right to be informed about the
      health of their child. We are confronted with an ethical and legal dilemma. The
      physician can take the role of a mediator: he has to support the autonomy of the
      adolescent with regard to the parental role.

PMID- 18630149
TI  - [Ignorance is no excuse...the legal statue of occupational risk of blood-borne
      infections (2)].

PMID- 18630150
TI  - [True and false mental disorders].

PMID- 18630151
TI  - [Mixing the courts with politics and public opinion].

PMID- 18630152
TI  - [Research on the dose assessment of those living near a nuclear waste processing
      plant].

PMID- 18630153
TI  - [New light shed on the physiopathology of sudden cardiac arrest].

PMID- 18630154
TI  - [Prevention is a combat sport].

PMID- 18630155
TI  - [Patient dignity and respect for the caregivers].

PMID- 18630156
TI  - [Postoperative results of hydrophilic expandable intraocular lenses ACQUA
      (Mediphacos) implantation].
AB  - PURPOSE: To assess postoperative outcomes of implanted hydrophilic expandable
      intraocular lenses ACQUA. MATERIAL AND METHODS: One hundred eyes of 75 patients
      with implanted intraocular lens (IOL) ACQUA were involved. IOLs were implanted
      during the period 2004 to 2005. The uncorrected visual acuity (UCVA) and the best
      corrected visual acuity (BCVA), refractive error and its spherical equivalent
      (SE) were measured preoperatively and 1 day, 1, 6, 12 months postoperatively.
      Possible postoperative complications were evaluated as well. The patients were
      divided into two groups: first group with the age-related macular degeneration
      (ARMD) and the second one without it. RESULTS: Sixty-five patients (90 eyes)
      finished the one-year follow-up period. Preoperative UCVA was 0.23 +/- 0.19, BCVA
      0.43 +/- 0.23 and SE + 0.15 +/- + 2.06 D (dioptres). Statistically significant
      differences between UCVA and BCVA one day and one month postoperatively were
      established. Six months after the operation and later on, the mean UCVA and BCVA
      were 0.61 +/- 0.26, and 0.82 +/- 0.23 respectively in all eyes, and 0.67 +/-
      0.24, and 0.9 +/- 0.17 respectively in the group of eyes without ARMD. Spherical
      equivalent was stable during the whole follow-up period, one year after the
      surgery it was -0.1 +/- 1.12 D in the group of all 90 eyes. The IOL central
      positioning in the bag was excellent in 86 eyes. Nd:YAG laser anterior
      capsulotomies were performed in two eyes due to the stricture of the anterior
      capsule and posterior capsulotomy was performed in one eye due to the fibrous
      secondary cataract. The ACQUA IOL had to be explanted from one eye because of
      recurrent acute non-infectious inflammation of the anterior segment. CONCLUSION:
      According to our experience, the IOL ACQUA Mediphacos shows good and stable
      postoperative outcomes.

PMID- 18630157
TI  - [Bilateral simultaneous dacryocystorhinostomy and conjunctivocystorhinostomy].
AB  - In patients with bilateral symptoms of lacrimal pathways occlusion, the endonasal
      dacryocystorhinostomy (EDCR) and conjunctivo-dacryocystorhinostomy (CDCR) may be
      performed simultaneously or consequently. The simultaneous bilateral surgery does
      not worsen the surgery results. The advantages of this procedure are one
      anesthesia only, only unsubstantial extension of the surgery duration, and
      shorter sick leave as well. The authors performed during the period from 1995 to
      2007 altogether 630 primary EDCRes and 117 CDCRes. In 92 patients, 184
      simultaneous dacryocystorhinostomies were performed. Out of 164 evaluated
      surgeries, the good results were obtained in 150 cases (91.5 %). Out of 40
      simultaneously performed CDCRes (20 patients), they were successful in 14
      patients. Unsuccessful they were in 3 patients in whom the silicone drainage
      implant was used.

PMID- 18630158
TI  - [The first experience with gold eyelid implants in facial nerve palsies].
AB  - The authors in a clinical study refer about their first experience of gold eyelid
      implants application in lagophthalmos treatment in facial nerve (cranial nerve
      VII) palsies. The implant, thanks its weight and the gravitation, facilitates to
      the patients to close their interpalpebral fissure. The implants are implanted in
      to the subcutis of the upper eyelid and are sutured to the anterior surface of
      the tarsal plate. The aim of the surgery is to lower the risk of the damage of
      the eye due to the exposure keratopathy and to allow the patients to control
      better the eyelid function. The gold as a material is well tolerated by the human
      body. The shape of the implant and the way of application ensure good functional
      results. Altogether 5 adult patients were operated on at the Department of
      Ophthalmology. The House-Brackmann score was used to evaluate the effectiveness
      of the surgery, or the stage of the closing of the interpalpebral fissure before
      and after the surgery. This score evaluates the palpebral sphincter function
      according the grade of involvement. The selection of the implants, their
      indication and surgery procedure are discussed.

PMID- 18630159
TI  - [Surgery of Duane retraction syndrome I: comparison of unilateral recession and
      resection versus bilateral medial rectus recessions].
AB  - The purpose of this comparative study was to evaluate a long-term efficacy of
      lateral rectus muscle resection in the affected eye of patients with Duane
      retraction syndrome (DRS) with esotropia and limited abduction and to compare it
      with bilateral medial rectus recessions. We reviewed and compared the data of the
      group A with 23 patients who underwent a recession-resection procedure and the
      group B with 26 patients in whom we performed medial rectus recessions. In each
      group, we evaluated pre- and postoperatively the ocular alignment, head position,
      ocular ductions, severity of retraction, and binocular visual field. Statistical
      analysis of the data was performed. Postoperatively, both groups had similar mean
      esotropia and mean face turns. However, the mean limitation of abduction in the
      affected eye was greater in the group B, mean adduction was also significantly
      worse in the group B. Globe retraction improved in all subjects of the group B,
      but worsened in 6 patients of the group A. Seventeen of 23 patients with Duane
      retraction syndrome, selected on the basis of esotropia, limited abduction, and
      mild retraction, benefited from a recession-resection procedure in the affected
      eye. The ability of abduction achieved higher level than in the group B after
      bilateral medial rectus recessions. We assume that unilateral recession-resection
      procedure should be performed in patients with mild retraction of the globe and
      good preoperative adduction.

PMID- 18630160
TI  - [H-test: a new alternative of Bagolini test for younger children].
AB  - The Small-House Test (H-test) which is easy to understand for the youngest
      children, was constructed as an alternative to the Bagolini test. The H-test is
      based on a pictogram of a night view of a small house. In its two windows, a
      polarized foil with crossed orientation is located. The picture is illuminated
      from behind. The viewer with polarized glasses, which are regularly used in
      stereo tests, perceives with his right eye the light coming through the right
      window, and with his left eye sees the light in the left window. The H-test, the
      Bagolini test and the Kubik test were performed in a group of 238 children; the
      mean age was 3.4 years. The mean age of children, who were able to perform the H
      test, was statistically significant lower as the age of children who were able to
      perform the Bagolini test. The youngest child who performed successfully the H
      test was two years old. In the group of 4.5 years old children, only 50% of them
      understood the Bagolini test. In the study, the determined parameters of the H
      test are discussed (specificity 94.7%, sensitivity 55.0%).

PMID- 18630161
TI  - [Disturbances of the plasma coagulation defects in retinal venous occlusions].
AB  - Occlusions of retinal veins (central and branch) represent multifactorialy
      conditioned disease involving presumably older patients, in whom the changes of
      retinal vessels caused by hypertension and atherosclerosis present the most
      important pathophysiological factors for development of this disease. In last
      years, the intensive scientific research is focused to the explanation of the
      role of the defects of the coagulations cascade. Especially in younger patients,
      the most often mentioned defect of the coagulations cascade is called as APC
      resistance. Up to 95% of all patients with APC-resistance are carriers of so
      called Leiden mutation. The aim of our study was to establish the prevalence of
      the ACP-resistance in 92 patients with central or branch occlusion of the retinal
      vein verified by means of angiography treated at the Department of Ophthalmology,
      Faculty Hospital, Olomouc, Czech Republic, EU, during the period 1999-2005. The
      control group consisted of 40 patients without any vascular, eye-related disease.
      In the group of patients with occlusion of the retinal vein, the prevalence of
      the APC-resistance was 10.9% and in the control group 5%. In the group of
      patients 55 years old and younger the prevalence of the ACP-resistance was 14.3%,
      in patients older than 55 years it was 5.6%. According to the relatively small
      groups of patients, the established difference did not reach the level of
      statistical evidence. Results of our study confirmed the conclusions of
      previously published papers that the prevalence of the APC-resistance is not
      significantly higher in patients with retinal vein occlusion according to the
      prevalence in controls.

PMID- 18630162
TI  - [Vasculitis of retinal vessels in lung tuberculosis--a case report].
AB  - The authors examined during the period 2003-2004 in an eye practice 652 patients
      who were hospitalized due to active lung tuberculosis. All patients were treated
      with combination of 3-4 antituberculotic drugs and the examination was performed
      to observe the possible side effects of ethambutol to the optic nerve. The most
      interesting was the ocular finding in a young man treated due to acute lung
      tuberculosis in whom during the antituberculotic therapy with combination of 4
      antituberculotics, the acute retinal vasculitis developed. This type of
      vasculitis is rare demonstration of ocular tuberculosis. The ocular finding
      resolved after starting the systemic corticoid therapy.

PMID- 18630163
TI  - [Immunohistochemical characterization of collagen IV in control corneas and in
      corneas obtained from patients suffering from posterior polymorphous corneal
      dystrophy].
AB  - The expression of all six chains of collagen IV was studied using the indirect
      fluorescent immunohistochemistry in seven control corneas and seven corneas
      obtained from patients suffering from the posterior polymorphous corneal
      dystrophy. Heterogeneous staining, especially in the epithelial basement membrane
      and Descemet's membrane, was observed in the control corneas. An increase of the
      staining intensity for the alpha1 and alpha2 chains was observed, especially in
      the Descemet's membrane and the corneal stroma in samples obtained from the
      patients compared to the control tissues.

PMID- 18630164
TI  - [Use of the international classification of mechanical injuries of the eye in
      clinical practice].

PMID- 18630165
TI  - [Why was enucleation of the left eye necessary in the famous Czech musician
      Otakar Sevcik 22. 3. 1852 - 18. 1. 1934?].

PMID- 18630166
TI  - [Neuropsychiatry].

PMID- 18630167
TI  - [Neuropsychiatry of epilepsy, stroke, Parkinson's disease and multiple
      sclerosis].
AB  - The assessement of behavior is common part of the neurological examination. This
      article reviews the behavioral and mood manifestations in four classical
      syndroms: Epilepsy, stroke, Parkinson's disease and multiple sclerosis.

PMID- 18630168
TI  - [Impulse control disorders and Parkinson's disease].
AB  - A variety of behavioral disorders occurring abruptly in patients with Parkinson's
      disease (PD) has been recently published and attracted considerable attention in
      the press. Taking the form of pathological gambling, compulsive shopping,
      addiction to Internet and to other recreational activities, hypersexuality or
      bulimia, impulse control disorders (ICD) related to PD are probably more frequent
      than previously appreciated and may have consequences as spectacular as
      disastrous for the involved patients. ICD are currently viewed as particular
      adverse reactions to antiparkinsonian medications, notably to dopamine agonists,
      and, accordingly, tend to improve or disappear when PD therapy is appropriately
      adjusted.

PMID- 18630169
TI  - [Hysteria: an historical entity, a psychiatric condition or a neurological
      disease?].
AB  - It has been suggested that hysteria had waned and was an old-fashioned,
      stigmatizing and false concept, reflecting the incapacity of the medical
      community to establish a diagnosis in certain situations. Nowadays, however,
      those disturbances, now referred to as conversion or dissociative disorders,
      still remain a frequent and incapacitating condition that every clinician faces.
      These past decades, several studies have tried to better describe their clinical
      presentation and their neurobiological mechanisms, with the help of the
      development of new neuroimaging techniques. If the neurobiological correlates are
      now better understood, efficient treatments are still lacking and only a
      multidisciplinary (general practitioners, neurologists and psychiatrists) and
      individually-tailored therapy might be beneficial to the patients.

PMID- 18630170
TI  - [Trouble with vision, hearing and concentration: Susac's syndrome ].

PMID- 18630171
TI  - [State of confusion, hallucinations and epileptic crisis].

PMID- 18630172
TI  - [Calcific uremic arteriolopathy (calciphylaxis)].
AB  - We present the case of a end stage renal failure patient treated with
      haemodialysis who developed painful nodules of the subcutis which progressed to
      ulcerative and necrotic lesions, gradually spreading. The diagnosis of calcific
      uremic arteriolopathy was made, based on histologic findings showing adipose
      tissue with necrotic areas and calcifications of the arterioles's media. We
      describe the clinical presentation of this syndrome which is associated with a
      high mortality and resume the actual conceptions about the pathogenesis, the
      diagnosis, prevention and treatment.

PMID- 18630173
TI  - [Refusal of urinary or salivary drug screening at school: the position of the
      SSAM (Swiss Society of Addiction Medicine)].

PMID- 18630174
TI  - [First results of gene therapy for Leber congenital amaurosis].

PMID- 18630175
TI  - [Pens and scalpels; medicine and literature].

PMID- 18630176
TI  - [Susanne Zetterberg, four bullets in the head].

PMID- 18630177
TI  - [Are we nearing the end of misleading titles?].

PMID- 18630178
TI  - [The hot and the cold of it].

PMID- 18630179
TI  - [Decrease of the prevalence of Helicobacter pylori infection in the Czech
      Republic].
AB  - Helicobacter pylori (Hp) is the most common chronic bacterial infection in
      humans. Hp has been demonstrated worldwide and in individuals of all ages. The
      overall prevalence of Hp infection has fallen dramatically in the Czech Republic
      over recent 15 years (from 70% in 1993 to 35% in 2006). This decrease can be
      explained mostly by the relatively favourable and improving socioeconomic
      conditions after the fall of communist regime. However, it is necessary to
      consider also the fundamental determinants of "modern times" that could cause
      gradual disappearing of Hp from the human "microbiome".

PMID- 18630180
TI  - [Medical ethics and ethicotherapy].
AB  - Elementary principles of Medical Ethics, namely the Nonmaleficience and
      Beneficence have not changed since antiquity till present. Not to harm the
      patient and give him the largest possible benefit with considering human rights
      and directives of true and open communication represent the basic rules in the
      treatment of chronic patients and in the palliative medicine. Some alternative
      methods, namely those used by medical doctors themselves and wrapped in
      scientific terms can seriously impair the patient both physically and
      psychically. A warning example is the ethicotherapy, one of the non-scientific
      methods, which induces an erroneous illusion of the association of therapy and
      ethics, and meanwhile it is strongly unethical.

PMID- 18630181
TI  - [Antley-Bixler syndrome or POR deficiency?].
AB  - Antley-Bixler syndrome (ABS) is a rare congenital disorder characterized by
      numerous craniofacial, skeletal and, in some cases, urogenital abnormalities
      resulting from disordered steroidogenesis. Known genetic causes in sporadic cases
      of ABS include dominant mutations in the fibroblast growth factor 2 receptor gene
      (FGFR2). Recent research shows surprisingly that symptoms of Antley-Bixler
      syndrome, combined with disordered steroidogenesis and urogenital anomalies, are
      caused by mutations in the POR gene that encodes NADPH-cytochrome P450
      oxidoreductase (CYPOR). CYPOR is a four domain-containing monomeric flavoprotein
      that contains two flavins, flavin adenine dinucleotide (FAD) and flavin
      mononucleotide (FMN), a binding site for NADPH, and the N-terminal sequence of 25
      amino acids which determines the microsomal localization of the protein. CYPOR is
      the electron donor to microsomally localized cytochromes P450 that participate in
      xenobiotic metabolism and steroidogenesis. Mutations in the POR gene lead to
      apparent diminished activity of some P450 enzymes. Association of CYPOR with ABS
      discloses new facts about this disease and recent research shows that patients
      with ABS-like skeletal anomalies, but with mutations in the POR gene and
      disordered steroidogenesis, represent a new disorder called POR deficiency.

PMID- 18630182
TI  - [Single nucleotide c.645+32c>T substitution in the APC gene is a non-pathogenic
      polymorphism appearing in about 16% of the Czech population].
AB  - BACKGROUND: Familial adenomatous polyposis is an autosomal dominant disease
      characterised by predisposition to colon polyposis and colorectal cancer and
      caused by germline mutations in the APC gene. The aim of the study was to
      establish the frequency of c.645+32C>T substitution in intron 5 of the APC gene
      in patients with multiple colon polyposis and in the general population and to
      determine if this substitution is a nonpathogenic polymorphism or a pathogenic
      mutation associated with multiple polyposis coli. METHODS AND RESULTS: The
      frequency of c.645+32C>T substitution in the APC gene was established in 170
      patients with the clinical phenotype of familial adenomatous polyposis or its
      attenuated form using denaturating gradient gel electrophoresis and direct
      sequencing. We tested a population of 200 noncancer persons using allelic
      specific polymerase chain reaction. The c.645+32C>T substitution was detected in
      27 of 170 patients with multiple colon polyposis (i.e. 15.9%). The substitution
      was found in 32 of 200 control persons, i.e. in 16%. The difference between
      patients with polyposis and the control group was not statistically significant
      (p = 0.979; chi-square test). CONCLUSIONS: Our results suggest that the
      c.645+32C>T substitution is a non-pathogenic single nucleotide polymorphism
      appearing in about 16% of the Czech population.

PMID- 18630183
TI  - [Conduct disorders in seven-year-old children--results of ELSPAC study 1. Co
      morbidity].
AB  - BACKGROUND: The interest of experts in conduct disorders (CD) research is growing
      during the last two decades. The research areas include the diagnostics,
      ethiopathogenesis and treatment and also the comorbidity, especially with the
      hyperkinetic syndrome incidence (Attention Deficit Hyperactivity Disorder--ADHD).
      This paper intends to describe the conduct disorder occurrence and its other
      manifestations of divergence found during the investigation of children followed
      in the prospective longitudinal study ELSPAC in seven, respectively eight years
      of their age. METHODS AND RESULTS: Data of 6100 seven-year-old children
      characterizing their behaviour was collected from mothers and attending
      physicians. In the school year during which this investigation phase took place
      2518 of the children reached eight years of age and their behaviour, temperament
      and school results were also evaluated by their teachers. The children were
      divided into three groups according to the presence or absence of the symptoms,
      which characterize conduct disorders (found by physicians): "stubborn
      negativistic behaviour", "inability to pay attention", "aggressiveness" and
      "inadequacy of reactions". The presence of two of these symptoms was found in 3%,
      presence of all four symptoms in additional 1.4% of children. Parents and
      teachers more often indicated various symptoms of hyperactivity in children with
      conduct disorders. CONCLUSIONS: In almost 5% of the ELSPAC cohort children in
      seven years of their age those symptoms were diagnosed, which match the Conduct
      Disorder criteria and Attention Deficit Hyperactivity Disorder (ADHD) criteria.
      In agreement with similar studies these frequent comorbidities were found: sleep
      disorders, psychomotor development disorders and laterality changes. The
      cognitive abilities evaluated by mothers and also teachers based on schoolwork
      results were more often worsened in children with conduct disorders. Various data
      indicating their worse social adaptability (which significantly disturbed the
      class) occurred more frequently in these children.

PMID- 18630184
TI  - [Standard diagnostic and therapeutic approach to the chronic infection with
      hepatitis C (HCV) virus].

PMID- 18630185
TI  - [Effects of mental stress on the health status of the accused during a criminal
      trial].
AB  - A court-sworn medical expert is sometimes authorized to pass a medical judgement,
      whether an older, from serious diseases suffering accused is able to take part in
      the criminal trial proceedings. The court-sworn medical expert is required to
      consider the accused's fitness, his mental and physical ability to appear in
      court, to understand the trial, to answer the questions of the judge, to defend
      himself, to put questions and objections against the witness's testimony, etc.
      Such medical expert's opinion is usually a task for a psychiatrist. Judgement of
      the ability of the accused to take part in the main court trial is of another
      character, especially when the accused is suffering from a serious disease, e.g.
      cardiovascular, pulmonary, gastrointestinal, haematological, tumorous or other.
      In this case the medical judgement is usually required from a doctor of internal
      medicine. Nevertheless, this is not an easy task for him. As far as these
      problems are concerned, the expert gathers only little experience of his own
      during his juridical practice. Similar cases have been extremely sporadically
      published in medical or juridical literature and if, then in common sense only.
      It is evident that the expert must face any possible aggravation of the accused's
      difficulties. At the same time the expert ought to take care lest the court trial
      should be inadequately extended and even should prevent the accused's avoidance
      in the main court trial. This paper tries to determine the basic rules for the
      court-sworn experts in the branch of internal medicine and would like to
      facilitate them to judge under which circumstances a seriously ill accused may
      appear in trial proceedings without exposing him to a serious damage of his
      health or even endangerment of his life.

PMID- 18630186
TI  - [Why do Czechs seldom cite the works of other Czech scientists? Does a "national
      character" exist?].
AB  - The author is an American psychiatrist of Czech origin, who has lived abroad
      since 1966, primarily in the USA. This contribution presents his viewpoint
      regarding several articles in Journal of Czech Physicians No. 1., 2008. The point
      of discussion is the purported lack of representation of Czech authors among
      authors cited by Czech doctors in articles which appear in domestic and also
      international medical journals.

PMID- 18630187
TI  - [Ten years after the latest revision International Anatomical Terminology].
AB  - Ten years ago, the latest revision of the Latin anatomical nomenclature was
      approved and published as Terminologia Anatomica (International Anatomical
      Terminology), and is acknowledged by the organization uniting national anatomical
      societies--International Federation of Associations of Anatomists. The authors
      concentrate on new terms included in the nomenclature and on the linguistic
      changes of terminology. The most frequent errors done by medical specialists in
      the usage of the Latin anatomical terminology are emphasized and the situation of
      eponyms in contemporary anatomy is discussed in detail as well. The last version
      of the nomenclature makes its way very slowly in the professional community and
      it is necessary to refer to positive changes and advantages it has brought. The
      usage of this Latin anatomical nomenclature version is suggested by the
      International Federation to follow in theoretical and clinical fields of
      medicine. The authors of the article strongly recommend using the recent revision
      of the Latin anatomical nomenclature both in the oral and written forms, when
      educating and publishing.

PMID- 18630188
TI  - Stress and depression among older residents in religious monasteries: do friends
      and God matter?
AB  - The purpose of this investigation was to explore how friendship and attach-0 ment
      to God provide protective benefits against stress and depression. Participants
      included 235 men and women, age 64 and older, residing in religious monasteries
      affiliated with the Order of St. Benedict. Hierarchical multiple regression
      analyses were completed to assess main and moderating effects of friendship and
      attachment to God relative to the influence of stress on depressive symptomology.
      Lower degree of friendship closeness (beta = -.12, p < .10) and greater
      insecurity with God (beta = -.15, p < .01) were directly associated with greater
      depressive symptoms. A significant three-way interaction (Stress x Friendship x
      Attachment to God) also existed relative to depressive symptoms (beta = .14, p <
      .05). Three "stress-buffering" mechanisms emerged relative to the influence of
      stress on depressive symptomology. First, a greater degree of friendship
      closeness in combination with less secure attachment to God represented a greater
      risk for depressive symptoms. Second, greater friendship closeness in combination
      with greater secure attachment to God reduced the risk for depressive symptoms.
      Third, lower degree of friendship closeness combined with less secure attachment
      to God diminished the noxious effects of stress on depressive symptoms. This has
      implications relative to how social and spiritual resources can be used to reduce
      stress and improve quality of life for older adults residing in religious
      communities.

PMID- 18630189
TI  - Age, education, and the gender gap in the sense of control.
AB  - High sense of control is related to benefits in many aspects of life, and
      education is known to be strongly related to sense of control. In this article we
      explore why women tend to feel a lower sense of control than men, and why the
      sense of control tends to be lower among the elderly than among younger people.
      In particular we explore the role played by education in explaining age- and
      gender differences in sense of control. The analysis is based on data from the
      first wave of the Norwegian NorLAG study, with a representative sample of adults
      aged 40-79 in 30 municipalities. We find that education accounts for some of the
      age and gender differences in sense of control, but the mediating effects of
      education are rather modest. We find an increasing gender gap in sense of control
      with age, and this increasing gap is completely explained by differences in
      education. Gender differences in sense of control is explained completely by four
      factors, which are related to resources and power; physical health, education,
      living with a partner, and leadership experience. Age differences in sense of
      control are only partially explained. Education, physical health and employment
      status cuts the age effect on sense of control to half. The effect of education
      on sense of control is partly mediated through what we suggest are tangible
      benefits of education, namely health, employment, and leadership experience.
      Education also influences individuals through socialization mechanisms. We view
      agentive orientation as a psychological benefit of education, and measure this
      characteristic with Bem's (1981) sex-role scale on masculinity. Agentive
      orientation completely explains the remaining effect of education on sense of
      control.

PMID- 18630190
TI  - Another wrinkle in the debate about successful aging: the undervalued concept of
      resilience and the lived experience of dementia.
AB  - The concept of "successful aging" is a contested discourse in gerontology. Two
      conflicting paradigms dominate the discussion: a health promotion activity model,
      and a model critical of the concept of successful aging. However, this study
      takes a different perspective and proposes that perhaps we have been striving for
      the wrong goal. The true quest as we age should not be for successful aging, but
      our goal should be for resilience, an undervalued and not fully examined concept
      in aging. Developing resilience is possible for many older adults regardless of
      social and cultural backgrounds or physical and cognitive impairments, unlike
      successful aging. This article discusses the concept of resilience from a
      theoretical resilience framework, applies the framework to a dementia population
      by providing two in-depth case studies of resilience among people with
      Alzheimer's disease, and concludes by advocating to move the resilience paradigm
      more front and center into the gerontological debate on successful aging.

PMID- 18630191
TI  - Effects of culture and age on the perceived exchange of social support resources.
AB  - This research explores the perceived exchange of social support resources of
      young, midlife, and older adults in the United States and Japan, and how
      perceptions of exchange may moderate attributions of control, difficulty, and
      success in attaining important life-goals. A survey was administered to
      participants in the United States and Japan who ranged in age from 17 to 70
      years. Results suggested culture and age to influence the designation of
      important life-goals, and to interactively moderate the perceived exchange of
      social support resources in the interpersonal contexts of family and business
      associates and co-workers. Furthermore, relationships between the perceived
      exchange of social support and perceptions of control and success in achieving
      life-goals indicated different intracultural effects. Overall, these findings
      suggest nuances in the perceived exchange of social support and social cognitions
      that reflect the cultural orientations of young, midlife and older adults in the
      United States and Japan. A culturally grounded model of social support is
      proposed and discussed.

PMID- 18630192
TI  - David C Jacks, MD: a president on behalf of physicians.

PMID- 18630193
TI  - Legal update 2008.

PMID- 18630194
TI  - Politics of payment in health care.

PMID- 18630195
TI  - MRSA in the hospital setting: prevention is the best cure.

PMID- 18630196
TI  - Physician performance measuring systems.

PMID- 18630197
TI  - Elaborative processing and conjunction errors in recognition memory.
AB  - Four experiments were conducted in order to examine the influence of elaborative
      processing at encoding on recognition memory conjunction lure errors. In these
      experiments, participants generated cues for compound words as wholes (e.g.,
      haywire) or as separate entities (e.g., hay, wire). Studied words were re
      presented in exact form (old) or recombined to form conjunction lures on the
      recognition test. Participants were asked to make old-new judgments and to
      indicate whether they had rejected items judged to be new because of recall of a
      studied item or because of lack of familiarity with an item. The results
      suggested that recall-to-reject processing and conjunction lure familiarity
      increased with both types of generation, although generation of cues for compound
      words as a whole did not influence conjunction lure error rates. An emphasis on
      processing each constituent of a compound word during encoding increased the
      familiarity of those constituents more than generation of a compound word as a
      whole, resulting in an increase in conjunction lure errors. These results suggest
      that both familiarity and recollection-based monitoring processes influence
      conjunction lure errors, and therefore support dual-process theories of
      recognition memory.

PMID- 18630198
TI  - Can the survival recall advantage be explained by basic memory processes?
AB  - Nairne, Thompson, and Pandeirada (2007) demonstrated a striking phenomenon: Words
      rated for relevance to a grasslands survival scenario were remembered better than
      identical words encoded under other deep processing conditions. Having replicated
      this effect using a novel set of words (Experiment 1), we contrasted the
      schematic processing and evolutionary accounts of the recall advantage
      (Experiment 2). Inconsistent with the schematic processing account, the
      grasslands survival scenario produced better recall than did a city survival
      scenario requiring comparable schematic processing. Recall in the grasslands
      scenario was unaffected by a self-reference manipulation. The findings are
      consistent with an evolutionary account that attributes the recall advantage to
      adaptive memory biases.

PMID- 18630199
TI  - Involuntary autobiographical memories in and outside the laboratory: how
      different are they from voluntary autobiographical memories?
AB  - In two studies, we compared the characteristics and retrieval times of
      involuntary and voluntary autobiographical memory under controlled laboratory
      conditions. A new laboratory task of involuntary autobiographical memories
      involved detecting vertical lines in a stream of stimuli with horizontal lines
      (an undemanding vigilance task) and recording any involuntary memories during the
      session. The majority of these memories were reported as being triggered by
      irrelevant cue phrases presented on the screen. Voluntary autobiographical
      memories were sampled via a standard word-cue method in Session 2. The results
      showed that involuntary memories were more specific and were retrieved
      significantly faster than voluntary memories. They were also more likely to be
      triggered by negative cues, whereas cue valence did not have any effect on the
      number of voluntary memories. Furthermore, laboratory involuntary memories did
      not differ from naturalistic involuntary memories recorded in a diary by the same
      participants (Study 2). Taken together, these results have important implications
      for current theories of autobiographical memory, and they open up interesting
      avenues for future research.

PMID- 18630200
TI  - Discriminating between changes in bias and changes in accuracy for recognition
      memory of emotional stimuli.
AB  - A debate has emerged as to whether recognition of emotional stimuli is more
      accurate or more biased than recognition of nonemotional stimuli. Teasing apart
      changes in accuracy versus changes in bias requires a measurement model. However,
      different models have been adopted by different researchers, and this has
      contributed to the current debate. In this article, different measurement models
      are discussed, and the signal detection model that is most appropriate for
      recognition is adopted to investigate the effects of valence and arousal on
      recognition memory performance, using receiver operating characteristic analyses.
      In addition, complementary two-alternative forced choice experiments were
      conducted in order to generalize the empirical findings and interpret them under
      a relatively relaxed set of measurement assumptions. Across all experiments,
      accuracy was greater for highly valenced stimuli and stimuli with high arousal
      value. In addition, a bias to endorse positively valenced stimuli was observed.
      These results are discussed within an adaptive memory framework that assumes that
      emotion plays an important role in the allocation of attentional resources.

PMID- 18630201
TI  - Effects of adult aging on utilization of temporal and semantic associations
      during free and serial recall.
AB  - Older adults show poorer performance than young adults at word list recall,
      especially for order information. In contrast with this temporal association
      deficit, older adults are generally adept at using preexisting semantic
      associations, when present, to aid recall. We compared the use of temporal and
      semantic associations in young and older adults' word list recall following both
      free recall and serial recall instructions. Decomposition of serial position
      curves confirmed that older adults showed weakened use of temporal context in
      recall in relation to young adults, a difference that was amplified in serial
      recall. Older adults' temporal associations were also less effective than young
      adults' when correlated with serial recall performance. The differential age
      decrement for serial versus free recall was accompanied by a persistent influence
      of latent semantic associations in the older adults, even when maladaptive for
      serial recall.

PMID- 18630202
TI  - Temporal isolation does not facilitate forward serial recall--or does it?
AB  - In numerous recent studies in short-term memory, it has been established that
      forward serial recall is unaffected by the temporal isolation of to-be-remembered
      items. These findings contradict the temporal distinctiveness view of memory,
      which expects items that are temporally isolated from their neighbors to be more
      distinct and hence remembered better. To date, isolation effects have only been
      found with tests that do not constrain output order, such as free recall. This
      article reports two experiments that, for the first time, report a temporal
      isolation effect with forward serial recall, using a running memory task in which
      the end of the list is unpredictable. The results suggest that people are able to
      encode and use temporal information in situations in which positional information
      is of little value. We conclude that the overall pattern of findings concerning
      temporal isolation supports models of short-term memory that postulate
      multidimensional representations of items.

PMID- 18630203
TI  - Working memory involvement in dual-task performance: evidence from the backward
      compatibility effect.
AB  - In three experiments, the authors supported the hypothesis that parallel response
      activation seen in dual-task performance results from holding Task 2 rules in
      working memory (WM) while performing Task 1. To this end, the authors used the
      backward compatibility effect (BCE; quicker primary responses when the Task 2
      response is compatible with codes of Task 1) as a marker for parallel response
      activation and manipulated WM load. Increasing the number of primary task rules
      from two to four did not modulate BCE, replicating Hommel and Eglau (2002), but a
      higher load condition, involving six primary task rules, reduced the BCE to
      nonsignificant levels. Experiment 3 further showed that WM is loaded by rules
      associating abstract stimulus categories to responses, and not by rules that
      associate individual stimuli to responses (S-R rules).

PMID- 18630204
TI  - How task errors affect subsequent behavior: evidence from distributional analyses
      of task-switching effects.
AB  - Switch costs in task switching are often assumed to reflect the strengthening of
      task-related associations. Recently, we provided evidence that committing an
      error leads to the strengthening of the wrong task (Steinhauser & Hubner, 2006).
      In the present study, we report how error-induced control compensates for the
      effects of error strengthening. We hypothesized that, although error detection
      cannot prevent an error from being strengthened, it initiates processes that
      suppress the negative consequences of error strengthening on subsequent trials.
      Because error-induced control is known to operate slowly, we predicted that a
      compensatory effect should be observable only for slow responses. In three task
      switching experiments, these predictions were confirmed by distributional
      analyses. The results extend our understanding of the interplay between
      procedural learning and executive control.

PMID- 18630205
TI  - The effect of stimulus availability on task choice in voluntary task switching.
AB  - The voluntary task switching paradigm allows subjects to choose which task to
      perform on each trial in a stimulus environment affording multiple tasks. The
      present study examined the effect of stimulus availability on task choice.
      Subjects viewed displays containing a digit and a letter and performed either an
      even/odd or a consonant/vowel judgment on each trial. The target stimuli appeared
      with a stimulus onset asynchrony (SOA) of 0, 50, 100, or 150 msec. The
      probability of performing the task associated with Stimulus 1 increased as SOA
      increased, indicating an effect of external or stimulus-driven factors on task
      choice. This effect of stimulus availability on task choice was greater when the
      response-stimulus interval was 400 msec than when it was 2,000 msec. This
      interaction of preparation interval and stimulus availability is explained within
      a model of task choice that includes both internal processes and external
      influences.

PMID- 18630206
TI  - Influence of display type and cue format on task-cuing effects: dissociating
      switch cost and right-left prevalence effects.
AB  - In previous studies of task switching and of the right-left prevalence effect,
      researchers have used a procedure in which the stimulus on each trial occurs in
      one of four quadrants, and responses are made by pressing one of two diagonally
      arranged response keys. Across these studies, discrepant effects of cuing
      interval have been reported. These discrepancies need clarification because cue
      based preparation effects are frequently interpreted as reflecting cognitive
      control processes. In Experiment 1, we compared performance with display formats
      used by Meiran (1996; Meiran, Chorev, & Sapir, 2000; small display, cues located
      at sides of quadrants and displayed until response) to study task switching and
      by Proctor and colleagues (Proctor, Koch, & Vu, 2006; large display, cues located
      at center of display and shown until target onset) to study right-left
      prevalence. We found a decrease in task-switch cost with increasing cuing
      interval with the Meiran display, but not with the Proctor display, but the right
      left prevalence effect was of similar size for the two display formats and was
      relatively unaffected by cuing interval. To determine the basis of the discrepant
      task-switch results, we used small and large displays in Experiments 2 and 3,
      respectively, with cue type and cue offset varied. With the side cues, the task
      switch cost decreased in all cases at the longer cuing interval, but with the
      centered cues, it decreased only when the display size was small. Thus, the
      effects of cuing interval on switch costs are sensitive to variations of display
      characteristics, whereas cuing interval and display characteristics have little
      influence on the right-left prevalence effect, suggesting that prevalence effect
      is due to processes that are independent from those producing the switch cost.

PMID- 18630207
TI  - The effects of payout and probability magnitude on the Allais paradox.
AB  - The Allais paradox decision bias was first offered as a challenge to the expected
      utility theory over 60 years ago. Although the Allais paradox is a standard
      challenge for normative theories of risky choice, its causes are not well
      understood. The present experiment uses two manipulations of the Allais paradox
      to investigate the commonly proposed probability-weighting explanation of the
      paradox. Reducing the magnitude of the outcomes did not affect the size of the
      Allais paradox, contradicting previous literature and supporting the probability
      weighting hypothesis. Reducing the probability of the nonzero outcomes to
      eliminate certainty reduced, but did not eliminate, the Allais paradox, a result
      inconsistent with probability weighting and other theories of the Allais paradox.
      The results suggest that the certainty effect alone cannot explain the Allais
      paradox.

PMID- 18630208
TI  - Inspecting visual mental images: can people "see" implicit properties as easily
      in imagery and perception?
AB  - Can people "see" previously unnoticed properties in objects that they visualize,
      or are they locked into the organization of the pattern that was encoded during
      perception? To answer this question, we first asked a group to describe letters
      of the alphabet and found that some properties (such as the presence of a
      diagonal line) are often mentioned, whereas others (such as symmetry) are rarely
      if ever mentioned. Then we showed not only that other participants could
      correctly detect both kinds of properties in visualized letters, but also that
      the relative differences in the ease of detecting these two types of properties
      are highly similar in perception (when the letters are actually visible) and
      imagery (when the letters are merely visualized). These findings provide support
      for the view that images can be reinterpreted in ways much like what occurs
      during perception and speak to the wider issue of the long-standing debate about
      the format of mental images.

PMID- 18630209
TI  - Eye movements and parafoveal word processing in reading Chinese.
AB  - In two experiments, a parafoveal lexicality effect in the reading of Chinese (a
      script that does not physically mark word boundaries) was examined. Both
      experiments used the boundary paradigm (Rayner, 1975) and indicated that the
      lexical properties of parafoveal words influenced eye movements. In Experiment 1,
      the preview stimulus was either a real word or a pseudoword. Targets with word
      previews, even unrelated ones, were more likely to be skipped than were those
      with pseudowords. In Experiment 2, all of the preview stimuli had the same first
      character as the target. Target words with same-morpheme previews were fixated
      for less time than were those with pseudoword previews, suggesting that
      morphological processing may be involved in extracting information from
      parafoveal words in Chinese reading. Together, the two experiments dealing with
      how words are processed in Chinese may provide some constraints on current
      computational models of reading.

PMID- 18630210
TI  - AIDS vaccine trials in India: ethical benchmarks and unanswered questions.

PMID- 18630211
TI  - Misconceptions about narco analysis.

PMID- 18630212
TI  - Narco analysis leads to more questions than answers.

PMID- 18630213
TI  - Obstetric practices related to HIV in Kerala.
AB  - This survey of obstetricians' knowledge and practices in two districts in Kerala,
      India, finds a number of unethical practices: most providers are unaware of the
      value of the rapid screening test for HIV, they do not give pregnant women the
      option to refuse testing; testing is done without counselling, private doctors
      refer pregnant women who test positive to government hospitals, and some health
      services have separate facilities for pregnant women who test positive.

PMID- 18630214
TI  - Patients' perspectives on medical information: results of an informal survey.
AB  - The autonomy of patients in making medical decisions is increasingly recognised
      globally, but is not fully adhered to in India. Information is the first step for
      a patient to be able to make a decision on his or her health care. The objective
      of this survey was to ascertain patients' perspectives on the amount of
      information given to them by health professionals. The results of interviews with
      222 patients show that perspectives vary, often according to the diagnosis. The
      amount of information given and the manner in which it is given are often not
      acceptable to the patient.

PMID- 18630215
TI  - Chikungunya fever, falciparum malaria, dengue fever, Japanese encephalitis... are
      we listening to the warning signs for public health in India?
AB  - The 2005-epidemic of Chikungunya fever highlights the weaknesses of public health
      in India. The failure to control mosquitoes, and the illnesses transmitted by
      them, has resulted in recurrent outbreaks all over the country. This is
      inevitable given the larger scenario: neglect of the basic requirements of
      health; poor political support for health; a weak public health capacity;
      centralised programmes for control based on selective interventions, and poorly
      planned development projects which have created conditions ideal for the outbreak
      of disease. All these issues are concerns for public health ethics and must be
      addressed to tackle the problems posed by mosquito-borne as well as other
      communicable diseases.

PMID- 18630216
TI  - Changing ethics in medical practice: a Thai perspective.
AB  - The pace of social change in Thailand has seen the rise of various medical
      services and a global clientele. Currently, medical tourism and cosmetic surgery
      have an important role in medical practice here. A growing medical market offers
      a range of services at competitive rates and high levels of efficiency. This
      essay provides an overview of medical practices in Thailand and their effect on
      ordinary people.

PMID- 18630217
TI  - Informed consent in an antiretroviral trial in Nigeria.
AB  - We examined the process of informed consent in an antiretroviral trial in
      Nigeria. A semi-structured questionnaire was administered to 88 out of 180 people
      enrolled in the trial. This covered all aspects of the information disclosed in
      the leaflet of the antiretroviral trial. We found that 75 (85 per cent) of the
      respondents knew that the purpose of the research was to test a new drug and 13
      (14 per cent) believed that they were receiving free treatment for HIV.
      Participants understood certain aspects of the research, especially the benefits
      and duration. Their understanding of the trial's risks and their right to refuse
      to participate and to withdraw was low. Their level of understanding was
      significantly related to age but not to gender, marriage, education, religion,
      employment and occupation. Signed informed consent is not a guarantee that
      participants have understood the information given to them and therefore made a
      voluntary decision to participate. Researchers should make sure that the process
      of obtaining informed consent achieves the desired outcome. This is especially
      important in the developing world where access to health care is limited,
      potential participants are poor and literacy levels are low.

PMID- 18630218
TI  - Ethical dilemma and resolution:a case scenario.
AB  - This article illustrates an ethical dilemma that I faced while treating an 86
      year-old woman at her home. The ethical dilemma was caused due to several factors
      such as the expectations of the client (client/consumer rights), organisational
      expectations (employer, governmental and payer-source regulations) and my own
      personal values (one's moral philosophies, perceived social responsibilities,
      sense of professional duty) and how they all interact with each other. The case
      is a classic example of a seemingly simple yet frequent dilemma encountered by
      occupational and physical therapists in the United States serving clients who are
      covered by Medicare (the government's health insurance) for home health. The
      article is aimed at highlighting the various ethical principles involved in
      clinical decision-making, and it suggests methods for resolution of ethical
      dilemmas. Although the article is based against the backdrop of the US health
      care system, students and health care practitioners globally can relate to it.

PMID- 18630219
TI  - Integrated response. Caring for survivors of sexual assault.

PMID- 18630220
TI  - Asia's organ farms.

PMID- 18630221
TI  - Drug promotional practices in Mumbai: a qualitative study.
AB  - We conducted a qualitative study to determine the range of promotional practices
      influencing drug usage in Mumbai. Open-ended interviews were conducted with 15
      senior executives in drug companies, 25 chemists and 25 doctors; focus group
      discussions were held with 36 medical representatives. The study provided a
      picture of what might be described as an unholy alliance: manufacturers, chemists
      and doctors conspire to make profits at the expense of consumers and the public's
      health, even as they negotiate with each other on their respective shares of
      these profits. Misleading information, incentives and unethical trade practices
      were identified as methods to increase the prescription and sale of drugs.
      Medical representatives provide incomplete medical information to influence
      prescribing practices; they also offer incentives including conference
      sponsorship. Doctors may also demand incentives, as when doctors' associations
      threaten to boycott companies that do not comply with their demands for
      sponsorship. Manufacturers, chemists and medical representatives use various
      unethical trade practices. Of particular interest was the finding that chemists
      are major players in this system, providing drug information directly to
      patients. The study also reinforced our impression that medical representatives
      are the least powerful of the four groups.

PMID- 18630222
TI  - Restructuring medical education.
AB  - This article explores instances of dysfunctional behaviour in resident doctors
      and examines the causes. It looks at the cultural competency training procedures
      for doctors in some institutions. There is a need for greater competency and
      diversity training of resident doctors. Counselling services also must be in
      place for addressing stress issues of doctors. These are important attributes
      looked for by WHO for accreditation.

PMID- 18630224
TI  - The importance of patient privacy during a clinical examination.

PMID- 18630223
TI  - Start sensitising medical students.

PMID- 18630225
TI  - HIV/AIDS legislation: an opportunity for health care reform.

PMID- 18630226
TI  - Working towards ethical organ transplants.

PMID- 18630227
TI  - Deceased-donor kidney transplantation in Iran: trends, barriers and
      opportunities.
AB  - Having enjoyed considerable success in kidney transplantation in recent years,
      Iran has been named the most active country in the Middle East Society for Organ
      Transplantation region in providing equitable quick, and intermediary-free access
      to affordable kidney transplantation for everyone regardless of gender and
      economic circumstances. We are, however, of the opinion that the Iranian model
      can benefit further from improving deceased-donor kidney transplantation,
      especially after a fatwa (Islamic edict) in the early 1980s lifted many religious
      and legal barriers. Deceased-donor kidney transplantation in Iran should be
      bolstered by establishing a transplantation model, increasing government funds,
      and encouraging participation of the general public in the Iranian Network for
      Transplant Organ Procurement. We recommend that an intensive media campaign be
      launched to heighten public awareness and more transplantation centres be
      involved in cadaveric transplantation with streamlined systems of cadaveric
      donations registration so as to facilitate the process of finding and relating
      the donors with potential recipients.

PMID- 18630228
TI  - The importance of "throwing money at" the problem of global health.
AB  - More funding from wealthy countries is required to improve health care and the
      infectious disease situation in developing countries. Although progress has been
      made, funds for fighting AIDS, tuberculosis, and malaria remain inadequate. These
      treatable and preventable diseases together kill over 6 million people every
      year. Funds are needed to improve access to existing medicines as well as to
      increase research and development of drugs. The idea that "throwing money at the
      problem is not going to solve it" rightly holds that increased funding is not
      sufficient for solving the health care problems of developing countries. In order
      to work, funds must be spent wisely. This does not mean that increased funding is
      unnecessary.

PMID- 18630229
TI  - Ethics in nutrition intervention research.

PMID- 18630230
TI  - It's time to rewrite our medical textbooks.

PMID- 18630231
TI  - Creating comprehensive ethics.

PMID- 18630232
TI  - Getting doctors to the villages: will compulsion work?

PMID- 18630233
TI  - Voices of people who have received ECT.
AB  - Electroconvulsive therapy (ECT) is controversial but widely practised in India.
      We elicited perspectives, using qualitative interviews, from patients who
      received ECT and their relatives. Ethical issues related to personal autonomy,
      right to information, competence, informed consent and consent by proxy are
      discussed. We suggest strategies to ensure a basic minimum standard for obtaining
      informed consent for ECT in India.

PMID- 18630234
TI  - Prescription of fixed dose combination drugs for diarrhoea.
AB  - Fixed-dose combinations (FDCs) of an antiprotozoal and an antibacterial, for
      treatment of diarrhoea, have been available in the Indian pharmaceutical market
      for about a decade. There is little evidence to substantiate this combination
      therapy. We evaluated 2,163 physician prescriptions for diarrhoea and found that
      59 per cent of prescriptions were for FDCs. This is unethical because prescribing
      such combinations exposes a patient to higher risks of adverse drug reactions and
      also increases the chances of drug resistance. Physicians' prescribing practices
      in India are influenced by socioeconomic factors and the pharmaceutical
      industry's marketing techniques that include giving incentives to physicians to
      prescribe certain drugs.

PMID- 18630235
TI  - Ethics committees and clinical trials registration in India: opportunities,
      obligations, challenges and solutions.
AB  - Registering clinical trials is considered an ethical and moral imperative. The
      launch of the Clinical Trials Registry-India provides opportunities to all in
      India to fulfil this imperative. The CTRI requires prospective registration,
      disclosure of all 20 items in the WHO Trial Registration Data Set and proof of
      ethics and regulatory clearances. Registration in the CTRI is voluntary. However,
      institutional research ethics committees have obligations. This article reviews
      these obligations and provides an example of how this can be achieved.

PMID- 18630236
TI  - Provider-initiated testing and counselling in India for HIV.

PMID- 18630237
TI  - Concerns about cosmetic surgery.
AB  - This article looks at some ethical challenges in cosmetic surgery. Enhancement
      versus therapy, risks, patient autonomy, beneficence and informed consent are
      issues that need to be considered when considering cosmetic surgery in today's
      world.

PMID- 18630238
TI  - Public-private partnerships for providing healthcare services.
AB  - The public-private partnership is an initiative to improve efficiency,
      effectiveness and equity in the provision of healthcare services. This essay
      comments on the lessons that should be learned from some examples of such
      partnerships in various Indian states.

PMID- 18630239
TI  - Public-private partnerships and global health equity: prospects and challlenges.
AB  - Health equity remains a major challenge to policymakers despite the resurgence of
      interest to promote it. In developing countries, especially, the sheer inadequacy
      of financial and human resources for health and the progressive undermining of
      state capacity in many under-resourced settings have made it extremely difficult
      to promote and achieve significant improvements in equity in health and access to
      healthcare. In the last decade, public-private partnerships have been explored as
      a mechanism to mobilise additional resources and support for health activities,
      notably in resource-poor countries. While public-private partnerships are
      conceptually appealing, many concerns have been raised regarding their impact on
      global health equity. This paper examines the viability of public-private
      partnerships for improving global health equity and highlights some key prospects
      and challenges. The focus is on global health partnerships and excludes domestic
      public-private mechanisms such as the state contracting out publicly-financed
      health delivery or management responsibilities to private partners. The paper is
      intended to stimulate further debate on the implications of public-private
      partnerships for global health equity.

PMID- 18630240
TI  - Opinions on suicide: a web-based discussion group in a programme on biomedical
      ethics in Pakistan.

PMID- 18630241
TI  - A terminally ill child in a public hospital.

PMID- 18630242
TI  - Ethics in nutrition intervention research:a response.

PMID- 18630243
TI  - The Thorat Committee report and the good doctor.

PMID- 18630244
TI  - Medical tourism in India: winners and losers.

PMID- 18630245
TI  - Trade secrets from a sperm bank in India. Interview by Jyotsna Agnihotri Gupta.

PMID- 18630246
TI  - Stem cell transplantation in India: tall claims, questionable ethics.

PMID- 18630247
TI  - Medical ethics education in India.

PMID- 18630248
TI  - Black money in white coats: whither medical ethics?
AB  - There has been a sea change in the ethos of medicine in India in recent decades.
      Academic dishonesty of an alarming nature has been reported in medical colleges.
      Moral degeneration and corruption have engulfed the establishment at the highest
      level. The head of the Medical Council of India was found guilty of corruption
      and stripped of his position a few years ago. Many professors in private medical
      colleges draw a part of their salary as "black"money. There is little discussion
      on this growing malady within the profession. Professional medical associations
      have turned a blind eye towards unethical practices; sincere efforts to take a
      stand on ethical medicine are lacking. Marginalisation of ethics raises questions
      about the professional integrity, moral sensitivity and social responsibility of
      practitioners of modern medicine in India.

PMID- 18630249
TI  - Fieldwork and social science research ethics.
AB  - Fieldwork as a part of social science research brings the researcher closest to
      the subject of research. It is a dynamic process where there is an exchange
      between the researcher, participants, stakeholders, gatekeepers, the community
      and the larger sociopolitical context in which the research problem is located.
      Ethical dilemmas that surface during fieldwork often pose a unique challenge to
      the researcher. This paper is based on field experiences during an action
      research study conducted with a human rights perspective. It discusses the role
      conflict that researchers face during fieldwork in a situation of humanitarian
      crisis. It raises issues pertaining to the need to extend the ethical decision
      making paradigm to address ethical dilemmas arising during the course of
      fieldwork.

PMID- 18630250
TI  - Therapeutic drug use in Bangladesh: policy versus practice.
AB  - The National Drug Policy (NDP), 1982, of Bangladesh was expected to make
      available essential, good quality drugs at affordable prices. This article gives
      an overview of the situation today, more than two decades after the Drugs
      (Control) Ordinance, 1982, was promulgated to implement the NDP. While there have
      been some successes, many of the goals of this initiative are yet to be achieved.
      Inadequate supply of essential drugs, substandard quality, uncontrolled drug
      prices and inappropriate uses of drugs are major problems in Bangladesh.

PMID- 18630251
TI  - The informed consent status for surgery patients in eastern Turkey: a cross
      sectional study.
AB  - This study assesses the quality of the informed consent process and satisfaction
      with the informed consent process, for surgery patients in Turkey. Four hundred
      and eighty three patients were interviewed after their surgeries. More than half
      of the patients were satisfied with the information on eight issues that
      pertained to the informed consent process. A majority of patients (91 per cent)
      were satisfied with the information regarding why an operation necessary.
      However, only 205 of 483 patients(42 per cent) indicated that they had received
      sufficient information on the potential side effects and complications of
      surgery. Patients' educational level and the type of surgery--urgent or elective-
      were associated with the satisfaction status.

PMID- 18630252
TI  - Bioethics and ayurveda.

PMID- 18630253
TI  - Medicine, ethics and the law.

PMID- 18630254
TI  - Is it okay to compensate a kidney donor?

PMID- 18630255
TI  - Inducements in health campaigns.

PMID- 18630256
TI  - [Strategy of molecular design of drugs: the unification of macro-properties and
      micro-structures of a molecule].
AB  - The interaction of a drug with the organism involves both the disposition of a
      drug by the organism and the action of a drug on the organism. The disposition of
      various exogenous substances, including drugs, complies with general rules. The
      underlying physical and chemical changes to different drugs in view of time and
      space, i. e. pharmacokinetics, share common characteristics, that is the tout
      ensemble of a molecule and its macroscopic properties convey direct effect on the
      pharmacokinetic behavior as the tendency and consequence of biological evolution.
      The action of a drug on the organism, on the other hand, implicates the physico
      chemical binding of a drug molecule to the target protein, which induces
      pharmacological and toxicological effects. The biological reactions, no matter
      beneficial or adverse, are all specific and individual manifestation of the drug
      molecule and determined by the interactive binding between definitive atoms or
      groups of the drug molecule and the macromolecular target in three-dimension.
      Such critical atoms, groups, or fragments responsible for the interaction reflect
      the microscopic structures of drug molecules and are called pharmacophore. In
      this context, a drug molecule is presumed as an assembly of macroscopic property
      and microscopic structure, with the macroscopic properties determining the
      absorption, distribution, metabolism and elimination of drugs and the microscopic
      structure coining pharmacological action. The knowledge of the internal
      relationship between macroscopy/microscopy and PK/PD conduces to comprehension of
      drug action and guides molecular drug design, because this conception facilitates
      the identification of structural features necessary for biological response, and
      the determination of factors modulating the physico-chemical and pharmacokinetic
      properties. The factors determining macro-properties include molecular weight,
      solubility, charge, lipophilicity (partition), and polar surface area, etc.,
      which are destined by molecular scaffolds and/or side chain(s) apart from
      pharmacophore. The features of micro-structures contributing to specific activity
      contain hydrogen bonding donor and acceptor, positive and negative charge
      centers, hydrophobic centers and centers of aromatic rings. Different
      combinations and spacial arrangements of these features determine the distinct
      activity presented. The macro-property and micro-structure are integrated into a
      single molecule, and are inseparable. The macro-property reflects overall
      contribution of atoms and groups in the micro-structure. On the other hand,
      structural changes aimed to adjust macroscopic property usually alter the
      relative position of the microscopic structure. The goal of molecular drug design
      is to integrate the macroscopic and microscopic factors in optimized manner. In
      the early stage of molecular design, both macroscopic property and microscopic
      structure should be considered to make pharmacodynamics, pharmacokinetics, and
      physico-chemical properties in optimal match. Therefore, it required the
      existence of structural overlapping among acceptable pharmacokinetics, visible
      developing potential and specific pharmacodynamics. The larger the scope of
      overlapping, the higher the possibility to be a drug.

PMID- 18630257
TI  - [Heat shock proteins: new target in cytoprotective and tumor therapy].
AB  - Heat shock proteins (HSPs) form the most ancient defense system in all living
      organisms. These proteins act as molecular chaperones by helping the refolding of
      misfolded proteins and assisting their elimination if they become irreversibly
      damaged. HSPs interact with a number of cellular systems and form efficient
      cytoprotective mechanisms. HSPs allow cells to adapt to gradual changes in their
      environment and to survive in otherwise lethal conditions. The events of cell
      stress and cell death are linked, and HSPs induced in response to stress appear
      to function at key regulatory points in the control of apoptosis. HSPs include
      antiapoptotic and proapoptotic proteins that interact with a variety of cellular
      proteins. Their expression levels can determine the fate of the cell in response
      to death stimulus. On the other hand, HSPs are overexpressed in tumor cells, and
      the inhibition of HSP90 has recently been regarded as a very promising tool to
      combat various cancers. HSPs can be secreted to circulatory system from a variety
      of cell types in response to stress. The secreted exogenous proteins act as
      cytokines and have potential modulatory functions in immune system. Cell surface
      bound HSP70 can render tumor cell more sensitive to natural killer cell-mediated
      cytolytic attack. Therefore, modulator of chaperone activities is becoming a new
      target of drug development, such as in apoptosis and tumor immunity fields.

PMID- 18630258
TI  - [Advances in the study of A2B adenosine receptor antagonists].
AB  - A2B adenosine receptor is involved in the control of mast cell degranulation,
      interleukin-8 synthesis and cell growth. A2B adenosine receptor antagonists may
      serve as novel drugs for asthma, Alzheimer' s disease, cystic fibrosis and type
      II diabetes. Therefore, seeking for the highly selective A2B adenosine receptor
      antagonists has been one of great interest. The molecular basis, structure
      activity relationship of selective A2B adenosine receptor antagonists and their
      interactions with A2B adenosine receptor were reviewed.

PMID- 18630259
TI  - [Recombination and identification of sense and antisence CyclinD1 eukaryotic
      expression vectors and the effects of the vectors on the proliferation of airway
      smooth muscle cell in asthmatic rats].
AB  - This study is to investigate the expression of CyclinD1 in asthmatic rats and
      construct expression plasmids of sense and antisense CyclinD1 gene and transfect
      them to asthmatic airway smooth muscle cell to study the effects of CyclinD1 on
      the proliferation of airway smooth muscle cells in asthmatic rats. CyclinD1 cDNA
      was obtained by RT-PCR of total RNA extracted from the airway smooth muscle in
      asthmatic rats. The sequence was inserted into eukaryotic expression vector
      pcDNA3.1 (+) to recombinate the sense and antisense pcDNA3.1-CyclinD1 eukaryotic
      expression vector. The two recombinations and vector were then separately
      transfected into airway smooth muscle cell in asthmatic rats by using liposome.
      The expression level of CyclinD1 was certificated by Western blotting analysis.
      The proliferations of ASMCs isolated from asthmatic rats were examined with cell
      cycle analysis, MTT colorimetric assay and proliferating cell nuclear antigen
      (PCNA) immunocytochemical staining. Results showed (1) Compared with control
      group, the content of CyclinD1 was significantly increased; (2) It was comformed
      by restriction endonucleasa digestion and DNA sequence analysis that the
      expression plasmid of sense and antisense CyclinD1 were successfully
      recombinated. There was significant change of CyclinD1 expression between vector
      and sense CyclinD1 transfected cells, and the expression level of CyclinD1 in
      ASMC transfected with antisense CyclinD1 was lower than that in vector
      transfected cells (P <0.01); (3) In the asthmatic groups, compared with the
      vecter group, the percentage of S + G2M phase, absorbance A value of MTT and the
      expression rate of PCNA protein in ASMC transfected with pcDNA3. 1-CyclinD1
      vector significantly increased. The values decreased remarkably in the pcDNA3,1
      as CyclinD1 group. Statistical analysis revealed that there were significant
      differences in these indicators of cell proliferation in three groups (P <0.01).
      In the normal groups, statistical analysis revealed that there were significant
      differences in the percentage of S + G2M phase, a value of MTT and the expression
      rate of PCNA protein in three groups (P <0.01). Sense CyclinD1 eukaryotic
      expression vectors could have a positive effect on the proliferation of ASMC,
      however the antisence one have a negative effect, which implicated that CyclinD1
      might contribute to the process of airway smooth muscle cell proliferation.

PMID- 18630260
TI  - [Screening of HIV-1 replication inhibitors by using pseudotyped virus system].
AB  - This study is to establish a cell-based pharmacological model targeting HIV-1
      replication for compounds screening and to screen compounds randomly selected
      from compounds library by using this pseudotyped viral system. The cell-based HIV
      1 replication pharmacological model was set up by HIV-1 core packed with
      vesicular stomatitis virus glycoprotein. The level of HIV-1 replication was
      presented by reporter genes expression (luciferase activity or percentage of GFP
      positive cells). When a compound has inhibitory effect on VSVG/HIV model,
      VSVG/MLV model would be used to test for specificity. Vesicular stomatitis virus
      glycoprotein can efficiently mediate HIV core into a wide range of host cells.
      Expression level of reporter genes showed dose-dependent manner with virion
      dilution. Among 500 compounds, three compounds dose-dependently inhibit HIV-1
      replication, but not MLV replication. VSVG/HIV pseudotyped viral system can be
      used as a pharmacological model for HIV-1 replication inhibitor screening.
      Compounds 2-methylthio-5-(4-methylbenzo)amido-l,3,4-thiadiazole, N-(3
      hydroxyphenyl)-2-(4-isobutylphenyl) propionamide, and N-(4-picolyl)-4
      methylbenzenesulfonamide can specifically inhibit HIV-1 replication with IC50 of
      1.92, 5.38, and 3.39 micromol L(-1) respectively.

PMID- 18630261
TI  - Effects of strophanthidin on intracellular calcium concentration in ventricular
      myocytes of guinea pig.
AB  - Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i)
      was investigated on isolated ventricular myocytes of guinea pig. Single
      ventricular myocytes were obtained by enzymatic dissociation technique.
      Fluorescent signal of [Ca2+]i was detected with confocal microscopy after
      incubation of cardiomycytes in Tyrode' s solution with Fluo3-AM. The result
      showed that Str increased [Ca2+]i in a concentration-dependent manner. The
      ventricular myocytes began to round-up into a contracture state once the peak
      level of [Ca2+]i was achieved in the presence of Str (10 micromol L(- 1)), but
      remained no change in the presence of Str (1 and 100 nmol L(-1)). Tetrodotoxin
      (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the
      response of cardiomycytes to Str (1 and 100 nmol L(-1)) , but had no obvious
      effects on the action of Str (10 micromol L(-1)). The elevation of [Ca2+]i caused
      by Str at all of the detected concentrations was partially antagonized by
      rynodine (10 micromol L(-1)) or the removal of Ca2+ from Tyrode's solution. In
      Na+, K+ -free Tyrode' s solution, the response of cardiomycytes in [Ca2+]i
      elevation to Str (10 micromol L(-1)) was attenuated, while remained no change to
      Str (1 and 100 nmol L(-1)). TTX, nisodipine, and high concentration of
      extracellular Ca2+ changed the response of cardiomycytes to Str at all of the
      detected concentrations in Na+, K+ -free Tyrode's solution. The study suggests
      that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is
      partially mediated by the extracellular calcium influx through Ca2+ channel or a
      "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at
      high (micromolar) concentrations was mainly due to the inhibition of Na+, K+ 
      ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic
      reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.

PMID- 18630262
TI  - Construction of the pharmacophore model of acetylcholinesterase inhibitor.
AB  - Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the
      same mechanism of action but are different in structural characteristics, the
      pharmacophore model for acetylcholinesterase inhibitor was constructed by the
      CATALYST system. The optimal pharmacophore model with three hydrophobic units, a
      ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight =
      3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05).
      This pharmacophore model will act on the double active site of
      acetylcholinesterase and is able to predict the activity of known
      acetylcholinesterase inhibitors that are used for clinical treatment of
      Alzheimer's disease (AD), and can be further used to identify structurally
      diverse compounds that have higher activity treating with Alzheimer's disease
      (AD) by virtual screening.

PMID- 18630263
TI  - [New dammarane type triterpene with cyclization at the side chain from oxidative
      alkaline-degradation products of PQS].
AB  - To study the oxidative alkaline-degradation products of PQS (Panax quinquefolium
      saponin), two compounds were isolated from the crude product of oxidative
      alkaline-degradation by silica gel column chromatography, Sephadex LH-20 column
      chromatography and recrystallized methods. On the basis of spectroscopic
      analysis, their structures were established as (12R, 20S, 24R)-20, 24; 12, 24
      diepoxy-24-deisopropyl-dammarane-3beta-ol (1) and (20S, 24R)-20, 24
      epoxydammarane-3beta3, 12beta, 25-triol (2). Compounds 1 and 2, dammarane type
      triterpene with cyclization at the side chain, were obtained for the first time
      from alkaline-degradation products of total ginsenosides of Panax quinquefolium
      L., compound 1 is a new compound.

PMID- 18630264
TI  - [A new phenylpropanoic acid derivatives from the roots of Ficus stenophylla].
AB  - Chemical constituents of the roots of Ficus stenophylla were isolated and
      purified by repeated column chromatography on silica gel and Sephadex LH-20.
      Their structures were elucidated based on physicochemical and spectral data. Five
      compounds were identified as methyl 3-(6-hydroxy-4-methoxybenzofuran-5-yl)
      propanoate (1), kaemferol (2), kampferol 3-O-beta-D-glucoside (3), quercetin (4)
      and tricin (5), separately. Compound 1 is a new phenylpropionic acid derivatives.
      All compounds were obtained from this plant for the first time.

PMID- 18630265
TI  - Phenolic glucosides from the leaves of Pieris japonica.
AB  - The aim of the study is to investigate chemical constituents of the leaves of
      Pieris japonica. The isolation and purification of the constituents were
      performed by various chromatography and spectral analysis. Three new phenolic
      glucosides, erythro-syringoylglycerol 4-O-beta-D-glucoside (1), 1-(2-beta-D
      glucopyranoxyl-4-methoxyl-6-hydroxyphenyl)-3-hydroxyl-l-propanone (3), erythro-l
      (4-hydroxyl-3-methoxyphenyl)-2-[4-(3-beta-D-glucopyranoxypropyl)-2 ,6
      dimethoxyphenoxy]-1, 3-propanediol (4), along with five known phenolic
      glucosides, syringoylglycerol 8-O-beta-D-glucoside (2), magnolenin C (5),
      syringaresinol mono-beta-D-glucoside (6), 3-(4-hydroxyl-3-methyphenyl)-1 
      propanol-l-O-beta-D-glucoside (7) and 3, 5-dimethoxyl-4-hydroxybenzyl alcohol 4-O
      beta-D-glucoside (8) were isolated and identified from the plant leaves.
      Compounds 1 and 2 inhibited significantly (P <0.01) the proliferation of murine T
      and B cells at concentration of 1 x 10(-6) mol L(-1), in vitro.

PMID- 18630266
TI  - [Electrocatalytic oxidation of glutathione at 10-methylphenothiazine modified
      carbon paste electrode and its practical analytical application].
AB  - The electrocatalytic oxidation of glutathione (reduced form GSH) at 10
      methylphenothiazine (MPT) modified carbon paste electrode (MPT/CPE) was
      investigated by cyclic voltammetry (CV). Although GSH itself showed a very poor
      electrochemical response at carbon paste electrode (CPE), the response could be
      greatly enhanced by using MPT/CPE, which enables a sensitive electrochemical
      determination of the substrate GSH. The reaction rate constant for catalytic
      oxidation was evaluated as (5.44 +/- 0.03) x 10(2) (mol L(-1))(-1) s(-1) by using
      chronoamperometry (CA). The catalytic oxidation peak current of GSH versus its
      concentration had a good linear relationship in the concentration range of 5.0 x
      10(-6) - 2.0 x 10(-3) mol L(-1) with the correlation coefficient of 0.9990, and
      the detection limit of 1.0 x 10(-6) mol L(-1) by linear sweep voltammetry (LSV).
      The method can be applied for the determination of GSH in injection samples with
      the satisfactory results.

PMID- 18630267
TI  - [Synthesis and mass spectrometric analysis of aristolochic acid-deoxyguanosine
      adducts].
AB  - To synthesize aristolochic acid (AA)-2'-deoxyguanosine 5'-monophosphate (dGp)
      adducts in vitro and develop a novel method for the characterization of the
      adducts using multiple mass spectrometric techniques. AA was incubated with dGp
      in vitro using either enzymatic activation (by xanthine oxidase) or chemical
      activation (by zinc) to synthesize AA-dGp adducts, and the reaction conditions
      were optimized. Crude extracts were analyzed by techniques of liquid
      chromatography-electrospray ionization/tandem mass spectrometry (LC-MS/MS) and
      high accuracy mass data and isotope pattern of super high resolution Fourier
      transform-ion cyclotron resonance mass spectrometry (FT-ICRMS). The quasi
      molecular ion peaks of the AA-dGp adducts were obtained in the negative ion mode.
      Analysis by electrospray ionization/tandem mass spectrometry (ESI-MS/MS) provided
      useful structural information about AA-dGp adducts. AA can bind covalently to the
      exocyclic amino group of deoxyguanosine to form AA-dGp adducts. MS analysis is a
      powerful tool to detect and identify AA-dGp adducts simply, rapidly and
      accurately.

PMID- 18630268
TI  - [Analysis of the main components of coptis-evodia herb couple by HPLC-DAD-MS].
AB  - A comprehensive HPLC-DAD-MS method was developed to study the chemical components
      of semi-bionic extract of Coptis-Evodia herb couple. The extract was isolated on
      a Hypersil BDS C18 column (4.6 mm x 200 mm, 5 microm) using acetonitrile-ammonium
      formic buffer as mobile phase by gradient elution. Detection was performed on DAD
      and MS equipped with an electrospray ionization (ESI) source by full scan and
      product full scan on positive mode. The chromatogram of Coptis-Evodia showed
      seventeen main peaks, eight of which were from Evodia while the others were from
      Coptis. By comparison of the retention time, the on-line UV spectra and MS
      spectra, four peaks were identified as jatrorrhizine, hydroxevodiamine, palmatine
      and berberine, and three peaks were deduced as epiberberine, columbamine and
      coptisine. In addition, berberine and palmatine were quantitatively determined.
      No new component was created in the semi-bionic extract of the herb couple, yet
      the solubilities of berberine and palmatine decreased.

PMID- 18630269
TI  - [Electrochemical behaviour of the adriamycin on the cobalt nanoparticles modified
      ITO electrode].
AB  - A cobalt nanoparticles modified ITO electrode (NpCo/ITO) was prepared by casting
      cobalt nanoparticles onto ITO electrode and the cobalt nanoparticles were
      synthesized by NaHB4 reduction. The electrochemical behaviors of adriamycin (ADM)
      on NpCo/ITO were studied. The modified ITO electrode was characterized by cyclic
      voltammetry (CV), scanning electron microscopy (SEM) and energy dispersive
      spectroscopy (EDS). In a 0.01 mol L(-1) PBS (pH 8.0) buffer solution, a sensitive
      reduction peak of ADM was obtained. A linear relationship is held between the
      peak current and ADM concentration in the range of 1.0 x 10(-8) - 2.0 x 10(-6)
      mol L(-1) with detection of 5.0 x 10(-9) mol L(-1)- by cyclic voltammetry (CV)
      response. The reduction process was irreversible with adsorption at the NpCo/ITO
      electrode. The modified electrode showed an excellent electrocatalytic activity
      for the ADM electrochemical reduction.

PMID- 18630270
TI  - [Preparation of the spin trapping probe, N-tert-butyl-alpha-phenylnitrone,
      nanoparticle and its affinity to hepatoma cells].
AB  - This article describes the preparation of the N-tert-butyl-alpha-phenylnitrone
      (PBN) liposomes and their related characteristics. The PBN liposomes were
      prepared by film dispersion-supersonic method and the formula of liposomes was
      optimized by orthogonal uniform design. RP-HPLC was used to qualify the amount of
      PBN that entered into the hepatoma cells. Necrosis rate was also investigated by
      fluorescence activated cell sorter (FACS) after PBN liposomes transfection.
      Result showed that the mean particle size, entrapment efficiency, and
      polydispersity of the resulting PBN-liposome were 137.5 nm, 71.52% and 0.286,
      respectively. PBN liposomes can enter into the tumor cell stably and they have
      higher affinity to hepatoma cell compared with free PBN resulting in a higher
      necrosis rate after transfection. These results provide a potential method for
      early diagnosis and treatment of cancer using specific spin trapping probe
      targeting tumor cells.

PMID- 18630271
TI  - [Permeabilities of rebamipide via different intestinal mucosa in the diffusion
      chamber in vitro].
AB  - The objective of this study is to investigate the permeabilities of rebamipide
      across the jejunal, ileal and colonic membranes in rat. The permeability (Papp)
      of rebamipide via rat intestinal membranes at concentration of 80 micromol L(-1)
      was evaluated by an in vitro diffusion chamber system after the membranes were
      isolated from the rat intestine. And the concentration of rebamipide in the
      receptor was determined by HPLC. As a result, the permeability of rebamipide
      across the jejunal or ileal membrane was higher than that across the colonic
      membrane, and the permeability of rebamipide in the ileal tissue from the serosal
      to mucosal direction was greater than that from the mucosal to serosal direction.
      Therefore, there was a regional difference in the permeability of rabamipide
      across the jejunum, ileum and the colon in rat. Also, the transporters in the
      intestinal mucosa as p-glycoprotein may not be involved in the transport of
      rebamipide.

PMID- 18630272
TI  - [Insulino-mimetic effects of bis (alpha-furancarboxylato) oxovanadium (IV) in
      vitro].
AB  - To study insulino-mimetic effects of bis(alpha-furancarboxylato) oxovanadium (IV)
      (BFOV), a orally active antidiabetic vanadyl complex, on glucose uptake and
      lipogenesis in isolated rat adipocytes were determined by using 2-deoxy-D-[3H]
      glucose and D-[3H]-glucose, respectively. Lipolysis was assayed by free fatty
      acids (FFA) released from isolated rat adipocytes treated with epinephrine. The
      results showed that BFOV, similar to insulin, concentration-dependently
      significantly enhanced the uptake of 2-deoxy-D-[3H]-glucose and the
      transformation from D-[3H]-glucose to lipid in isolated rat adipocytes, with the
      EC50 values of (0.31 +/- 0.08) mmol L(-1) and (0.49 +/- 0.12) mmol L(-1),
      respectively. Moreover, BFOV markedly inhibited FFA release from isolated rat
      adipocytes treated with epinephrine, and the IC50 value was (0.30 +/- 0.20) mmol
      L(-1). BFOV had insulino-mimetic effects such as enhancing glucose uptake and
      lipogenesis, as well as inhibiting lipolysis.

PMID- 18630273
TI  - [Upper-airway obstructive diseases related to brain-cardiovascular and metabolic
      consequence].

PMID- 18630274
TI  - [Research on the relationship between obstructive sleep apnea hypopnea syndrome
      and nocturnal laryngopharyngeal reflux].
AB  - OBJECTIVE: To study the relationship between obstructive sleep apnea hypopnea
      syndrome (OSAHS) and nocturnal laryngopharyngeal reflux (LPR), and discuss the
      possible mechanism. METHODS: Nineteen OSAHS patients had PSG, nocturnal pH and
      intraesophageal pressure monitoring simultaneously. The sleep stage, body
      position and pressure change were recorded during every reflux event The
      relationship between obstructive sleep apnea (OSA) and LPR was analyzed. RESULTS:
      Among 19 OSAHS patients, 6 cases were found to have LPR, and 63 reflux events
      were recorded. There was a negative relationship between the severity of OSAHS
      and nocturnal mean laryngopharyngeal pH value, but relationship between OSA and
      reflux events is not statistically significant. The intraesophageal pressure (t =
      3.211, P = 0. 007) and upper esophageal sphincter (UES) pressure (t = 2.234, P =
      0.046) were statistically different between the patients with and without LPR.
      There was a positive relationship between the mean value of intraesophageal
      pressure and the whole night mean laryngopharyngeal pH value (r = 0.592, P =
      0.033). CONCLUSIONS: There was significant relationship between severity of OSAHS
      and nocturnal laryngopharyngeal pH value. OSAHS patients are more likely to have
      esophageal reflux which could increase LPR, Compared with OSAHS patients without
      LPR, UES pressure during the night decreased significantly in those cases with
      LPR, it suggested this could be another mechanism of LPR.

PMID- 18630275
TI  - [Comparison of the sleep architecture and symptom of inattention-hyperactivity in
      children with obstructive sleep apnea hypopnea syndrome before and after
      surgery].
AB  - OBJECTIVE: To observe the symptoms of inattention, hyperactivity among
      obstructive sleep apnea hypopnea syndrome (OSAHS) children, also to investigate
      the effects of surgery (tonsillectomy and adenoidectomy or adenoidectomy alone)
      on the changes of sleep architecture and inattention-hyperactivity score (IHS).
      METHODS: Between June 2004 and may 2007, eighty children diagnosed as OSAHS with
      overnight polysomnography (PSG) were included in this study, only sixteen
      children had complete pre-op and post-op PSG data. Thirty children with vocal
      cord nodules were selected as control group. DSM-IV-derived IHS was evaluated by
      neurologist. All OSAHS children accepted surgery (tonsillectomy and adenoidectomy
      or adenoidectomy alone) and IHS evaluation. The pre-op and post-op sleep
      architecture and IHS were compared with that of control group. RESULTS: (1) The
      median IHS 80 OSAHS children was higher than that it in control group (0.89 vs
      0.17) and the difference was significant (Z = -4. 276, P < 0.05). After surgery,
      it showed a significant reduction in IHS (0.44 vs 0.89, t = 6.219, P < 0.05). (2)
      Twenty-five OSAHS children had pre-op IHS greater than 1.25 and nine had post-op
      IHS greater than 1.25, while only three children in control group had IHS greater
      than 1.25. The difference was statistically significant (chi2 = 5.192, 9.56
      respectively, P < 0.05). (3) For sixteen OSAHS children who had both pre-op and
      post-op PSG data, a decrease in the percentage of phase 1 sleep and an increase
      in the percentage of phase 2 sleep, slow wave sleep (SWS) and rapid eye movement
      (REM) sleep were observed in six months after surgery and the difference was
      significant (t = 12.2, -5.4, -6.3, - 8.1 respectively, P < 0.001). After surgery,
      apnea-hypopnea index (AHI) decreased from 13.9 times/h to 1.5 times/h while
      lowest saturation of blood oxygen (LSaO2) increased from 0.855 to 0.940 (t = 5.3,
      - 3.7 respectively, P < 0.01). REM sleep percentage and LSaO2 was still lower
      than that of control group six months after surgery. CONCLUSIONS: Children with
      OSAHS showed significantly impaired attention and hyperactivity as compared with
      control group. Improvement of behavior and sleep architecture were observed after
      adenoidectomy and tonsillectomy.

PMID- 18630276
TI  - [Growth retardation in children with obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To observe changes of growth, body composition and biochemical markers
      associated with growth (IGF-1) in prepubertal children with obstructive sleep
      apnea syndrome (OSAHS). METHODS: Thirty-one children aged 3-10 years with OSAHS
      were followed up for 1 year after the corresponding surgery. During the same
      period of time, 20 children of similar age without OSAHS (excluded any other
      diseases that could result growth retardation or hypoxemia) were also followed up
      for 1 year. PSG, height, weight as well as insulin-like growth factor-1 (IGF-1)
      were measured during the preoperative period, 3 months, 6 months and 1 year after
      surgery in patient group. The same indexes were measured before surgery, and only
      height and weight were recorded after surgery in the control group. Wilcoxon
      signed- rank test and Mann-Whitney U test are used to analyze the data. RESULTS:
      The lowest oxyhemoglobin saturation of the patient group (0.88) is significantly
      lower than that of the control group (0.98), and was found increased at the 6
      months post-op follow up (0.97, U = 238.5, P > 0.05), no significant change was
      found at the 1 year follow up. The post-op AHI (6 months after surgery) of the
      patient group (6.0/h) decreased to the similar level of the control group (0/h, U
      = 240.0, P > 0.05), and was similar to 1 year after surgery. Height of the
      patient group (116 cm), which was lower than the control group (U = 127.0, P <
      0.001), significantly increased 1 year (138 cm) after the corresponding surgery
      (Z = 3.726, P < 0.01), and reached the similar levels of the control group (137
      cm) 1 year after the surgery (U = 123.5, P > 0.05). The serum IGF-1 levels of the
      patient group (33.7 ng/ml), which were significantly lower than those of the
      controls preoperatively (44.1 ng/ml, U = 206.0, P < 0.05), increased to similar
      levels with the controls 6 months after the operation (50.3 ng/ml, U = 261.0, P >
      0.05), and the 1 year post-op follow up was similar to the control group too
      (48.6 ng/ml, U = 163.0, P > 0.05). CONCLUSIONS: The cure of OSAHS could
      accelerate growth in prepubertal children, and the serum IGF-1 levels increases
      at the same time. The growth retardation is presumed in children with OSAHS.

PMID- 18630277
TI  - [Influence on antidiuretic hormone secretion in children with obstructive sleep
      apnea hypopnea syndrome].
AB  - OBJECTIVE: To explore the influence of obstructive sleep apnea hypopnea syndrome
      (OSAHS) in children on the secretion of antidiuretic hormone (ADH). METHODS:
      Thirty pediatric patients with OSAHS were examined with polysomnography (PSG) and
      urinary volume was recorded during sleep, and vein blood was sampled in deep
      sleep to detect the level of ADH in serum using radioimmunoassay technique, which
      were performed before and after adenotonsillectomy. Among twenty heath children
      were also detected the secretion of ADH as normal controls. RESULTS: After
      surgery, apnea-hypopnea index (AHI) decreased (from 17.4 +/- 2.6 to 3.3 +/- 1.4,
      t = 27.68, P < 0.001), lowest SaO2 increased (from 0.783 +/- 0.134 to 0.954 +/-
      0.062, t = 6.45, P < 0.001). The level of ADH in OSAHS patients (63.1 +/- 35.2)
      ng/L was much lower than that in health children (85.1 +/- 22.2) ng/L (t = 2.75,
      P < 0.01). The serum ADH level in postoperative patients (83.1 +/- 21.2) ng/L was
      increased significantly compared with that of preoperative (t = 2.56, P < 0.05),
      and no statistical difference versus that of health children (t = 0.17, P >
      0.05). Nycturia volume of preoperative OSAHS children (492 +/- 90) ml was
      significant higher than that of postoperative (332 +/- 56) ml or normal controls
      (346 +/- 62) ml (t was 7.85 and 6.43, both P < 0.001). There was no significance
      in nycturia volume between postoperative group and control group (t = 0.77, P >
      0.05). CONCLUSIONS: After adenotonsillectomy in children with OSAHS caused by
      adenotonsillar hypertrophy, the sleep pattern and ADH secretion could become
      normal.

PMID- 18630278
TI  - [Myiasis in nasal cavity, maxillary sinus and ethmoidal sinus: a case report].

PMID- 18630279
TI  - [Loudness growth functions between children with normal hearing and sensorineural
      hearing loss by the modified Contour test].
AB  - OBJECTIVE: To compare the loudness growth of normal hearing children and children
      with sensorineural hearing loss (SNHL) by the modified Contour test. METHODS: The
      loudness growth function were obtained in 26 ears with normal hearing and 25 ears
      with SNHL using the modified Contour test. Retesting were carried out 2 or 3
      weeks later after the initial test. The results were analyzed by the univariate
      analysis of variance. RESULTS: There was significant difference in loudness
      growth between normal hearing group and groups with SNHL of different degrees (F
      = 1368.32, P < 0.001), and also between different loudness categories (F =
      682.21, P < 0.001). Large differences were observed in the dynamic range between
      normal hearing children and children with sensorineural hearing loss (F = 214.26,
      P < 0.001). The following results were found in the loudness growth in children
      with SNHL: the more serious the hearing loss was, the more rapid the loudness
      growth and the smaller the dynamic range. The test-retest reliability of loudness
      growth function obtained in normal hearing and hearing-impaired group was highly
      correlated. The results of modified contour test showed good reliability.
      CONCLUSIONS: When fitting hearing aids for a child the result of individual
      loudness growth should be obtained as possible as it could be drawn to reach the
      best listening saturation for the child. The modified contour test was a vivid
      and easy-to-do test for children, also with good reliability. In order to fit
      hearing aids properly for children, it was worth applying the modified contour
      test in clinic.

PMID- 18630280
TI  - [Efficacy and safety of cluster immunotherapy for 154 patients with allergic
      rhinitis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of cluster immunotherapy with
      Dermatophagoides pteronyssinus for allergic rhinitis. METHODS: One hundred and
      fifty-four patients with allergic rhinitis to Dermatophagoides pteronyssinus were
      allocated to receive specific immunotherapy in a 6-week cluster schedule during
      the incremental-dose phase. Thereafter, these patients received maintenance-dose
      injection at 6-week intervals until the end of 1 year of treatment. Symptom
      scores and medication scores were used to evaluate the clinical efficacy and
      adverse reactions were recorded. A rhinoconjunctivitis quality of life
      questionnaire (RQLQ) was completed in the baseline and after one year treatment.
      RESULTS: Cluster immunotherapy significantly reduced the symptom scores and total
      medication score of patients enrolled (P < 0.01). The immunotherapy group also
      had a significant improvement in the Rhinoconjunctivitis Quality of Life
      Questionnaire. During the one-year of treatment, there were 26 systemic adverse
      reactions (0.75% of all injection) in 9 patients (5.9%) and no fatal systemic
      reactions occurred. CONCLUSIONS: The cluster immunotherapy is efficacious and
      safe to treat allergic rhinitis.

PMID- 18630281
TI  - [Quality of life outcome of patients with chronic rhinosinusitis and nasal
      polyposis after endoscopic sinus surgery and its influencing factors].
AB  - OBJECTIVE: To explore the quality of life (QOL) outcome of patients with chronic
      rhinosinusitis (CRS) after endoscopic sinus surgery (ESS) and its influencing
      factors. METHODS: prospective trial was conducted to survey the QOL status of 120
      CRS patients undergoing ESS, in contrast that of 200 healthy individuals passing
      health examination, at the baseline and at 12-months after operation by Medical
      Outcomes Study Short Form-36 (SF-36) and Sino-Nasal Outcome Test-20 (SNOT-20).
      QOL changes and its influencing factors were analyzed statistically. RESULTS: (1)
      By the assessment of SF-36, the scores of 6 domains were less than that of
      healthy individuals preoperatively (P < 0.01). After 6 months, the scores of
      these domains resumed normal level and the proportion of scores also restored
      normally (P > 0.05). (2) By the assessment of SNOT-20, the total scores of 20
      items and 5 most important items of patients were more than that of healthy
      objects (P < 0.01). After 9 and 12 months, the former and latter returned to
      normal, respectively (P > 0.05). In 12 months setting, the proportion of scores
      also restored normally (P > 0.05). (3) According to the survey of SNOT-20, we
      concluded the following equation: convalescent time (months) = 39--(normal
      scores/preoperative scores) x 50, by which the time of coming back to normal QOL
      status can be computed. (4) By analysis of Logistic Regression, residence in city
      or country, course of disease, extension of diseased sinus, and coexistence of
      nasal polyposis or not were correlated to the preoperative QOL scores; working
      environments, surgical extension, and preoperative scores of QOL were correlated
      to the score difference between pre and post operation. CONCLUSIONS: CRS patients
      undergoing ESS could obtain entirely normal QOL status at 12 months
      postoperatively, so we suggest that the essential follow-up period should last at
      least one year. The risk factors influencing patients QOL status preoperatively
      includes residence in country, longer course of disease, more extension of
      diseased sinus, and coexistence of nasal polyposis. The risk factors hindering
      the improvement of QOL status postoperatively includes exposure to indoor working
      environments, insufficient surgical extension, and lower preoperative QOL scores.

PMID- 18630282
TI  - [Posttraumatic anosmia: olfactory event related potentials and MRI evaluation].
AB  - OBJECTIVE: Using olfactory event related potentials (OERP) and magnetic resonance
      to evaluate olfactory function in patients with posttraumatic anosmia. METHODS:
      Twenty four patients with posttraumatic anosmia were reviewed retrospectively. A
      thorough medical history, physical examination, nasal endoscopy, T&T olfactory
      testing, olfactory event-related potentials, brain computed tomography scan and
      magnetic resonance image of olfactory pathway were performed in all patients.
      RESULTS: Subjective olfactory testing indicated 20 of 24 patients were birhinal
      anosmia, 2 with right nostril anosmia and left impairment, 2 with left anosmia
      and right normal. No OERP were obtained in 24 (20 were birhinal, 4 was
      monorhinal), except 4 cases with single nostril. Magnetic resonance imaging
      revealed the injures to the olfactory bulbs (100%), rectus gyrus (91.7%), orbital
      gyrus (67%), olfactory tracts (8%) and temporal lobes (8%). CONCLUSIONS: OERP can
      objectively evaluate posttraumatic olfactory function, and magnetic resonance of
      olfactory pathway can precisely identify the location and extent of injures.

PMID- 18630283
TI  - [Selective neck dissection on the treatment of neck metastases in 63 patients
      with squamous cell carcinoma of hypopharynx].
AB  - OBJECTIVE: To analyze the prevalence and distribution of cervical node metastases
      in squamous cell carcinoma of hypopharynx and evaluate the efficacy of selective
      neck dissection (SND) on the treatment of the neck metastases. METHODS: A
      retrospective review was performed for 63 patients with squamous cell carcinoma
      of hypopharynx from January 1990 to December 2004. Lymph nodes were clinically
      negative in 17 patients and positive in 46 patients. There were 15 unilateral
      SND, 22 bilateral SND and 16 modified radical neck dissections (MRND).
      Ipsilateral MRND or radical neck dissections (RND) and contralateral SNDs were
      performed in 10 cases. Forty-eight patients were followed up and the follow-up
      interval ranged from 24 to 143 months and the median was 41 months. RESULTS:
      Lymph nodes were pathologically negative (pN0) in 22 and positive (pN +) in 41
      patients. A total of 106 positive nodes were found in 95 neck dissections. The
      distribution of the positive nodes were as follows: Level II 47.2% (50/106),
      Level III33.0% (35/106), Level IV11.3% (12/106), Level V2.8% (3/106), Level VI
      5.7% (6/106). Contralateral nodal metastases and recurrence were observed in both
      cN0 and cN + cases. There were 18 neck recurrent cases. High incidence of neck
      recurrence after SND was found in level II and III. The 3-year estimated survival
      rate analysis were 58.1% for the pN0 and 44.9% for pN1 and 41.1% for pN2
      patients. Cox regression analysis suggested N stage was the most important
      prognostic factor. The risk ratio was 1.7 in pN1 and 2.2 in pN2. CONCLUSIONS:
      Lymphatic metastases was the most significant prognostic factor of hypopharyngeal
      squamous cell carcinoma. Bilateral selective neck dissection, when carefully
      indicated, offers functional advantages without oncologic compromise.

PMID- 18630284
TI  - [Co-location of ACh-sensitive BK channels and L-type calcium channels in type II
      vestibular hair cells of guinea pig].
AB  - OBJECTIVE: To explore the mechanisms of the influx of calcium ions during the
      activation of ACh-sensitive BK channel (big conductance, calcium-dependent
      potassium channel) in type II vestibular hair cells of guinea pigs. METHODS: Type
      II vestibular hair cells were isolated by collagenase type IA. Under the whole
      cell patch mode, the sensitivity of ACh-sensitive BK current to the calcium
      channels blockers was investigated, the pharmacological property of L-type
      calcium channel activator-sensitive current and ACh-sensitive BK current was
      compared. RESULTS: Following application of ACh, type II vestibular hair cells
      displayed a sustained outward potassium current, with a reversal potential of (
      70.5 +/- 10.6) mV (x +/- s, n = 10). At the holding potential of -50 mV, the
      current amplitude of ACh-sensitive potassium current activated by 100 micromol/L
      ACh was (267 +/- 106) pA (n = 11). ACh-sensitive potassium current was potently
      sensitive to the BK current blocker, IBTX (iberiotoxin, 200 nmol/L). Apamin, the
      well-known small conductance, calcium-dependent potassium current blocker, failed
      to inhibit the amplitude of ACh-sensitive potassium current at a dose of 1
      micromol/L. ACh-sensitive BK current was sensitive to NiCl2 and potently
      inhibited by CdCl2. NiCl2 and CdCl2 showed a dose-dependent blocking effect with
      a half inhibition-maximal response of (135.5 +/- 18.5) micromol/L (n = 7) and
      (23.4 +/- 2.6) micromol/L (n = 7). The L-type calcium channel activator, (-) -Bay
      K 8644 (10 micromol /L), mimicked the role of ACh and activated the IBTX
      sensitive outward current. CONCLUSION: ACh-sensitive BK and L-type calcium
      channels are co-located in type II vestibular hair cells of guinea pigs.

PMID- 18630285
TI  - [A case of squamous cell carcinoma from a branchial cleft cyst].

PMID- 18630286
TI  - [Effects of CD4+ T cell transplantation on facial motoneuron survival in nude
      mice model with facial nerve axotomy].
AB  - OBJECTIVE: To investigate the specific T cell subpopulation and the relationship
      with facial motoneuron in immune deficiency mouse model with facial nerve
      paralysis, so as to find information for new strategy of facial palsy treatment.
      METHODS: Firstly, purifying the CD4+ T cell from wild type mouse and
      reestablishing the immune function of nude mouse by infusing the CD4+ T cell
      through the tail vein a week before the surgery. Then the all nude mouse (BALB/c
      background) and wild type mouse (BALB/c background) were subjected to a right
      facial nerve axotomy. Then the mouse was studied by application and assessment
      with fluorogold retro tracer at specific time. After collecting the slices of
      brain stem three days post the operation, the facial motoneurons was observed
      under fluorescence microscope, then analyzed and counted with the software Image
      Pro Plus5. 1. RESULTS: The number of survival facial motoneuron in the group with
      CD4+ T cell transplantation and control group was (3444.5 +/- 84.2, x +/- s) and
      (3013.2 +/- 65.3) respectively. There was significant difference of the number of
      survival facial motoneurons between nude mouse transplanted with CD4+ T cell and
      PBS at three days post the operation (t = 5.52, P = 0.0003). But there was no
      significant difference of survival facial motoneurons between nude mouse
      transplanted with CD4+ T cell and wild type mouse three days post the operation
      (t = 0.49, P = 0.6347). It was the transplantation of CD4+ T cell that rescued
      the survival facial motoneuron to the level of wild type. CONCLUSIONS: CD4+ T
      cell have the ability to rescue the injuring facial motoneuron from death. It may
      suggest that there is a critical role of the specific T cell subpopulation in
      facial nerve repair and regeneration.

PMID- 18630288
TI  - [A randomized double-blinded controlled research about the efficacy of
      antithrombotic and vasodilator in curing].

PMID- 18630287
TI  - [Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally
      advanced nasopharyngeal carcinoma: a meta-analysis].
AB  - OBJECTIVE: To determine the value of concurrent chemoradiotherapy in patients
      with locoregionally advanced nasopharyngeal carcinoma from the mainland of China.
      METHODS: Data were extracted from randomized trials comparing chemotherapy plus
      radiotherapy with radiotherapy alone in locally advanced nasopharyngeal
      carcinoma. Actuarial rates of survival and distant metastases were calculated.
      The followed electronic databases were searched the Chinese Biomedicine database,
      Pubmed, Medline, Embase and Cochrane library; Data were extracted by tow
      reviewers and Review manager 4.1 software was applied for statistical analysis.
      RESULTS: Eighteen trials with 1993 patients were include according to the
      including criterion. The 3-year overall survival rate of the chemoradiotherapy
      group and the radiotherapy group were 68.47% and 56.38% respectively, and the 5
      year overall survival rate of the two groups above were 51.91% and 41.09%
      respectively, while the distant metastases rate of the chemoradiotherapy group
      and the radiotherapy group were 26.19% and 38.71% respectively. The result
      demonstrated that chemoradiotherapy increased overall survival by 12% at 3 years,
      and 11% at 5 years after treatment. After chemoradiotherapy, the rate of distant
      metastasis was reduce by 12%. CONCLUSIONS: In patients with locoregionally
      advanced nasopharyngeal carcinoma, chemoradiotherapy significantly improves
      overall survival at 3 years, and 5 years compared with radiotherapy alone.

PMID- 18630289
TI  - [A case report of facial nerve schwannoma whose clinical manifestation similar to
      glomus jugular tumor].

PMID- 18630290
TI  - [Tumors of the paranasal sinuses induced hypophosphatemic vitamin D resistant
      osteomalacia: a case report].

PMID- 18630291
TI  - [Repetitiously multiple and deteriorative neurofibroma in pars laryngeal
      pharynges: a case report].

PMID- 18630292
TI  - [Carcinosarcoma of the maxillary sinus: a case report].

PMID- 18630293
TI  - [A case of hereditary hemorrhagic telangiectasia with multiple organ
      malformation].

PMID- 18630294
TI  - [Bilateral acoustic neuromas].

PMID- 18630295
TI  - From the 'de-parted', tales of sorrow: hair today and gone tomorrow.

PMID- 18630296
TI  - The last word in anthropogenic global warming: Find alternative energy sources.

PMID- 18630297
TI  - Thoughts under a Haitian sky.

PMID- 18630298
TI  - Recent advances in otolaryngology-head and neck surgery.

PMID- 18630299
TI  - Smoke-free workplace ordinance passes.

PMID- 18630300
TI  - Compromising Missouri continues.

PMID- 18630301
TI  - Sinusitis in the pediatric population.
AB  - A greater utilization of endoscopes in the evaluation and surgical management of
      pediatric sinus disease, in addition to the increased sensitivity added by CT
      diagnosis of sinusitis, has given physicians a heightened awareness of sinusitis
      in children. Advances in immunology, both diagnostic and therapeutic, have
      created a more multidisciplinary approach to the management of sinusitis in the
      pediatric patient. This article will discuss important co-existent diseases, the
      medical management of pediatric sinusitis, the indications for surgical
      intervention and outcomes and sequellae of the management of this disease
      process.

PMID- 18630302
TI  - Allergic rhinitis in children.
AB  - Allergic rhinitis (AR) is common in children. The prevalence has been reported to
      be 20-40% in the pediatric population worldwide. The cause and risk factors for
      the development of AR are incompletely defined but involve both genetic and
      environmental elements. Although allergic rhinitis is seldom a severe or life
      threatening disease, it can have profound effects on daily living and development
      of a child. AR has multiple comorbidities and is closely related to asthma and
      atopic dermatitis. Often the child's parents will concentrate on comorbid
      diseases only and will not mention or be concerned by symptoms of their child's
      allergic rhinitis. Diagnosis of AR is made by a combination of history and
      physical exam. The causative allergens are identified by allergy testing. Allergy
      testing is done in vivo (skin testing) or in vitro (Rast testing). Treatment ofAR
      can include allergen avoidance, pharmacotherapy and immunotherapy. All three
      therapies are effective and safe in children.

PMID- 18630303
TI  - Implantable hearing devices.
AB  - Implantable hearing devices are becoming more common practice in assisting
      hearing impaired patients who do not benefit enough from conventional
      amplification devices such as hearing aids. This article illustrates the benefits
      obtained by patients who are recipients of the BAHA (Bone Anchored Hearing Aid)
      or cochlear implants. Patients receive significant hearing benefit from
      implantable hearing devices and practitioners should be aware of the criteria for
      referral and the significant benefits that these devices can bring to their
      patients.

PMID- 18630304
TI  - Voice disorders: abuse, misuse and functional problems.
AB  - Having a vocal complaint is not uncommon, especially among professional voice
      users. Medically managing hoarseness is often delayed because the physician or
      patient fails to understand the vocal behavior that precipitated the voice
      disorder. Improper breathing and/or abusive vocal patterns are the main
      predisposing factors to functional voice disorders, the most common category of
      vocal pathology. Successful management of functionalvoice disorders includes
      identifying and then modifying aberrant vocal and breathing patterns. Unless
      these changes are made, a vocal disorder will either persist or commonly recur.

PMID- 18630305
TI  - Management of oral cavity carcinoma.
AB  - Oral cavity cancer continues to be a major health issue in the state of Missouri,
      largely due to the high rate of tobacco use. Pretreatment evaluation and planning
      should be done by a multidisciplinary team. Surgical resection is the primary
      method of treatment. Adjuvant therapy is frequently needed to control
      intermediate and advanced disease. There are significant functional effects of
      surgery; reconstructive efforts are focused on restoring the patient to as normal
      a condition as possible. Acoordinated approach by an experienced team can achieve
      good local control and minimize morbidity.

PMID- 18630306
TI  - Contemporary surgical management of non-medullary thyroid malignancy.
AB  - This article reviews the clinical features of well differentiated thyroid cancer
      and examines various tools used in the evaluation of patients, in both the
      primary and the recurrent settings. Contemporary treatment strategies, with an
      emphasis placed on surgical treatment are revisited. Non-surgical modalities,
      including the use of radioactive iodine, external beam radiotherapy and
      chemotherapy are discussed.

PMID- 18630307
TI  - Image-guided surgery of the paranasal sinuses and skull base.
AB  - The application of image-guidance technology to sinonasal and skull base
      procedures has ushered in a new era of surgical approaches to conditions
      affecting this region. The ability of image-guidance systems to provide the
      surgeon with enhanced anatomic localization during endoscopic procedures offers
      the potential for fewer intraoperative complications and improved clinical
      outcomes. In a remarkably short time, navigation systems have gone from being a
      curious novelty to a near-necessity in some complex skull base procedures.

PMID- 18630308
TI  - The management of obstructive sleep apnea in adults.
AB  - Obstructive Sleep Apnea (OSA) is characterized by recurrent, complete or partial
      airway closure during sleep. It is a potentially hazardous condition and
      appropriate treatment should be strongly advised to all OSA patients. The primary
      mode of OSA management is Continuous Positive Airway Pressure (C-Pap).
      Asignificant number of OSA patients can be also managed successfully with surgery
      by a variety of newer surgical techniques which emphasize a more physiologic and
      less morbid surgical approach to the upper airway.

PMID- 18630309
TI  - Sleep-disordered breathing in children.
AB  - Pediatric Sleep Disordered Breathing (SDB) is often associated with behavioral
      problems, poor school performance, decreased quality of life and increased
      healthcare utilization. Adenotonsillectomy (T&A) leads to resolution of SDB in
      over 80% of children and results in behavioral improvement and better quality of
      life. Obese children, as well as those afflicted with craniofacial, genetic or
      neuromuscular disorders, are at greater risk for SDB than healthy children. This
      report highlights the need to recognize and treat SDB in children.

PMID- 18630310
TI  - Initial approach to the patient with impaired consciousness.
AB  - Patients presenting with impaired consciousness are often challenging to diagnose
      and treat. Etiologies are multiple and varied. Obtaining an accurate history and
      physical exam is often difficult with the altered patient. It is essential for
      the physician initially evaluating the patient to have a prioritized, systematic
      approach. The primary goals are to stabilize the patient, rapidly recognize and
      treat reversible causes, and disposition the patient appropriately to avoid
      potential morbidity and mortality.

PMID- 18630311
TI  - Assessing cardiac CT--advantages & current limitations. Part II: Clinical
      utility.
AB  - The media's frenzy towards the imaging capabilities of 64-slice cardiac computed
      tomography (CCT) is not without cause. CCT allows non-invasive visualization of
      the coronary arteries, coronary artery bypass grafts, and the presence of
      atherosclerosis. CCT is not limited to the assessment of coronary vasculature,
      but can yield information about other causes of chest pain such as aortic
      dissection, or pericardial disease. Other applications for the high resolution
      scanner include anatomical assessment of congenital heart disease, post
      myocardial infarction complications, pulmonary embolism and aortic and peripheral
      arterial atherosclerosis and aneurysm evaluation. Finally, non-contrast CCT
      allows for quantification of coronary calcification which provides important
      prognostic information. As CT technology evolves, it is paramount for clinicians
      to understand when it is clinically appropriate to use CT coronary angiography
      (CTCA).

PMID- 18630312
TI  - Savings needed to fund health insurance and health care expenses in retirement:
      findings from a simulation model.
AB  - MODELING RETIREE HEALTH COSTS: This Issue Brief examines the uncertainty of
      health care expenses in retirement by using a Monte Carlo simulation model to
      estimate the amount of savings needed to cover health insurance premiums and out
      of-pocket health care expenses. This type of simulation is able to account for
      the uncertainty related to individual mortality and rates of return, and computes
      the present value of the savings needed to cover health insurance premiums and
      out-of-pocket expenses in retirement. These observations were used to determine
      asset targets for having adequate savings to cover retiree health costs 50, 75,
      and 90 percent of the time. NOT ENOUGH SAVINGS: Many individuals will need more
      money than the amounts reported in this Issue Brief because this analysis does
      not factor in the savings needed to cover long-term care expenses, nor does it
      take into account the fact that many individuals retire prior to becoming
      eligible for Medicare. However, some workers will need to save less than what is
      reported if they keep working in retirement and receive health benefits as active
      workers. WHO HAS RETIREE HEALTH BENEFITS BEYOND MEDICARE?: About 12 percent of
      private-sector employers report offering any Medicare supplemental health
      insurance. This increases to about 40 percent among large employers. Overall,
      nearly 22 percent of retirees age 65 and older had retiree health benefits in
      2005 to supplement Medicare coverage. As recently as 2006, 53 percent of retirees
      age 65 and older were covered by Medicare Part D, 24 percent had outpatient
      prescription drug coverage through an employment-based plan. Only 10 percent had
      no prescription drug coverage. INDIVIDUALLY PURCHASED MEDICARE SUPPLEMENTS, 2008:
      Among those who purchase Medigap and Medicare Part D prescription drug coverage
      at age 65 in 2008, men would need between $79,000 and $159,000 with median
      prescription drug expenses (50th percentile and 90th percentiles, respectively),
      and between $156,000 and $331,000 with prescription spending that is at the 90th
      percentile. Women would need between $108,000 and $184,000 with median
      prescription drug expenses (50th and 90th percentiles, respectively), and between
      $217,000 and $390,000 with prescription spending that is at the 90th percentile.
      The savings needed for couples would range from $194,000 at the 50th percentile
      to $635,000 at the 90th percentile. EMPLOYMENT-BASED BENEFITS, 2008: Among those
      who have employment-based retiree health benefits to supplement Medicare, but who
      must pay their own premiums, men would need between $102,000 and $196,000 in
      current savings (50th and 90th percentiles, respectively) to cover health care
      costs in retirement. Women would need between $137,000 and $224,000,
      respectively, due to their greater longevity. The savings needed for couples
      would range from $154,000 to $376,000. INDIVIDUALLY PURCHASED MEDICARE
      SUPPLEMENTS, 2018: Among those who purchase Medigap and Medicare Part D
      prescription drug coverage at age 65 in 2018 (currently age 55), men would need
      between $132,000 and $266,000 with median prescription drug expenses (50th and
      90th percentiles, respectively), and between $261,000 and $555,000 with
      prescription spending that is at the 90th percentile. Women would need between
      $181,000 and S308,000 with median prescription drug expenses (50th and 90th
      percentiles), and between S364,000 and $654,000 with prescription spending that
      is at the 90th percentile. The savings needed for couples would range from
      $325,000 at the 50th percentile to S1,064,000 at the 90th percentile. RETIREE
      HEALTH MAY BE DRIVING LONGER TIME IN THE WORK FORCE: The declining availability
      of retiree health benefits may partly explain the rising labor force
      participation rate among individuals ages 55-64. Between 1996 and 2006, the labor
      force participation rate increased from 67 percent to 69.6 percent for men and
      from 49.6 percent to 58.2 percent for women.

PMID- 18630313
TI  - Some intraspecies differences in antigens on the surface of certain living human
      cells.
AB  - Surface antigens of several types of living cells of human origin were partially
      characterized with hyperimmune antisera prepared in the rabbit against living
      HeLa cells and living, uncultured, full-term, human amnion cells.
      Hemagglutination, mixed-agglutination, and direct and indirect immunofluorescence
      (FAB) techniques were employed. With these techniques and fractional absorption
      procedures, common and specific cell antigens were detected on the surface of
      several human living cells: uncultured and primary amnion, two established human
      cell lines (RP Am 1 and U amnion) of presumed normal origin and two (HeLa and HEp
      2) of presumed malignant origin, and human erythrocytes. None of the antigens
      were found on NCTC 2555 mouse cells. The human cells possessed species-related
      antigens demonstrable by hemagglutination. After removal of the hemagglutinins by
      absorption with human erythrocytes, antibody in high titer for the homologous
      cells was detected by FAB methods. In addition, some changes in antigens on the
      surface of amnion cells during primary culture were observed. Finally, an antigen
      was found on HeLa and HEp-2 cells, by use of anti-HeLa serum absorbed with human
      erythrocytes and RP Am 1 cells, that was not found on either human erythrocytes,
      uncultured amnion cells, or on the cells of the two established amnion cell
      lines. At the dilutions used in the tests, antibodies to the ABO blood group
      isoantigens, Forssman hapten, or adsorbed serum proteins could not account for
      the antigens detected. The possibility that Mycoplasma sp. antigens were
      responsible for the reactions was inconsistent with the results. The specificity
      of the FAB methods on living cells was confirmed.

PMID- 18630314
TI  - Shope papilloma virus. II. A comparison of several methods for purification of
      the virus.
AB  - Four methods for preparation of Shope papilloma virus have been compared. These
      comprise: (1) alternate centrifugation at low and high speed after grinding with
      alundum and saline, (2) purification with a fluorocarbon after similar
      extraction, (3) extraction with the aid of 2-mercaptoethanol and purification by
      alternate low- and high-speed centrifugation, and (4) extraction with 2
      mercaptoethanol followed immediately by centrifugation to equilibrium in CsCI. It
      is necessary to remove CsCI before chemical analysis, and this has been
      accomplished by chromatography on Sephadex G-75. After banding, the virus from
      preparation (4) appears homogeneous in the electron microscope. The
      deoxyribonucleic acid (DNA) contents of the preparations were (1) 7.8, (2) 8.3,
      (3) 8.0, and (4) 11.9 percent of total nucleoprotein. At equal inputs of DNA,
      there was no significant difference in infectivity of any of the preparations.
      Method (4) is simpler than the others and results in a higher yield of a
      homogeneous preparation.

PMID- 18630315
TI  - Studies on the epidemiology of bovine leukemia.
AB  - Characteristics of a female bovine population for a 19-county area of Michigan
      are defined. Cases of bovine leukemia in dairy cattle for this area are reported
      for the years 1962-65. The reported annual leukemia incidence for female Holstein
      cattle is 19 per 100,000. Reliable incidence rates could not be computed for the
      other four dairy breeds, since they comprised only 11 percent (approximately
      50,000) of the dairy cattle population. An age-specific incidence graph shows a
      rather consistent increase in incidence as age advances, reaching 36 cases per
      100,000 Holstein animals 8 years of age and over. The evidence indicates that
      size of herd has an influence on the incidence rate of leukemia--the rate being
      higher in large herds than in small.

PMID- 18630316
TI  - Pathogenicity for rats of a strain of chicken sarcoma virus.
AB  - The RBI rat tumor, induced with cell suspensions from chicken sarcoma B77, is
      pathogenic for chicks as well as for rats. Cell suspensions from RBI tumors
      induced sarcomas in 100 percent of inoculated chicks. Cell suspensions of this
      chicken sarcoma induced early RBA sarcomas in 50 percent of 171 rats. Most of
      these rats died within 4 weeks after inoculation. The early tumors regressed in
      15 of the 85 tumor-bearing rats, and the animals died of cystic hemorrhagic
      disease. The sarcoma was induced in 9 animals within 50 to 70 days after
      inoculation, and cystic hemorrhagic disease developed in 117. None of the 171
      rats remained free from either tumor or cyst and only 12 survived for 3 months or
      longer. The tumors induced in rats were transplantable into rats and after
      transplantation of early-appearing tumors, tumors and cysts developed. Virus
      strongly infective in chicks was demonstrated by cell-free filtrates and virus
      preparations from RBI and RBA rat sarcomas induced by chicken sarcoma cells. Cell
      suspensions from the wall of small cysts induced tumors in chicks and cystic
      hemorrhagic disease and tumors in rats.

PMID- 18630317
TI  - Suspension cell culture and in vivo and in vitro chromosome constitution of mouse
      leukemia L1210.
AB  - An in vitro culture of mouse leukemia L1210 was established, along with
      conditions for optimal growth in suspension culture. L1210 showed a high
      requirement for folic acid in comparison with other cell lines in vitro. As few
      as 10 viable cells cultured in vitro killed DBA/2 mice. Cells from ascites showed
      a sharp mode of 40 chromosomes, with a minute marker chromosome and an extra
      small, T-type (telocentric) chromosome. Cells cultured in vitro showed a mode of
      40 or 41 chromosomes and contained the minute marker but not the extra-small
      chromosome; in addition, an m-type (metacentric) marker chromosome was observed
      in the cultured cells. This in vitro system should lend itself to evaluation of
      karyogenesis in relation to carcinogenesis, drug effects, and cytogenetic
      dynamics, as well as to nutritional and metabolic studies.

PMID- 18630318
TI  - Immunology of the mouse mammary tumor virus: comparison of mammary tumor virus
      with the agent found in C3Hf/Crgl mice.
AB  - C3Hf/Crgl mice, containing no biologically active mammary tumor virus,
      nonetheless possess both type-B virus particles and a component which cross
      reacts serologically with the mammary tumor virus. Neutralization studies and the
      immunodiffusion assay for measuring the antigenicity of the mammary tumor virus
      indicate that transfer of the virus particles from C3Hf to BALB/cCrgl mice is
      accompanied by transfer of the cross-reacting antigenic component.

PMID- 18630319
TI  - Mortality of radiation chimeras in relation to the number of transplanted bone
      marrow and lymph node cells.
AB  - Injection of lymph node cells along with therapeutic doses of bone marrow cells
      into irradiated animals can cause death if the lymphoid cells are capable of
      reacting against the host animal. The mortality and time of death are
      proportional to the number of lymphoid cells injected. Death can be as late as 70
      days after irradiation. Injection of bone marrow cells alone can cause death but
      only when very large numbers of cells are given and only in certain donor-host
      combinations. Great numbers of bone marrow cells raise the death rate after
      injection of lymph node cells in certain donor-host combinations but counteract
      this killing effect in other combinations. The number of immunologically
      competent cells in bone marrow from both CBA and C57BL mice is small. In CBA mice
      an equivalent number of immunologically competent cells was estimated in 20 x
      10(6) bone marrow and in 0.05 to 0.1 x 10(6) lymph node cells; for C57BL mice
      these figures were 50 x 10(6) bone marrow and 0.4 x 10(6) lymph node cells. To
      explain why bone marrow can apparently offset the killing effect of lymphoid
      cells, it is postulated that immunologically tolerant cells developing from
      pluripotent stem cells in bone marrow compete with immunologically competent
      lymphatic cells.

PMID- 18630320
TI  - Studies on fused, a mutant gene producing ovarian tumors in Drosophila
      melanogaster.
AB  - Flies homozygous for the mutant gene fused (fu) are characterized by fused wing
      veins, a maternal effect upon embryogenesis, and ovarian tumors. A number of
      mutant alleles have been studied and all exhibit this same syndrome. The rate at
      which ovarian tumors develop is characteristic for each allele. This rate was
      shown to be independent of modifying genes and unaffected by the maternal
      cytoplasm. The rate is also temperature-sensitive, tumors appearing more slowly
      at 18 than at 25 degrees C. Females heterozygous for all possible combinations of
      these alleles were produced, and, in all 21, tumors were observed in the compound
      females. Cases of dominance, complementarity, and interference were observed with
      reference to certain allelic combinations. A model is proposed to explain the
      diverse effects on development of the fused gene and also the interaction of the
      alleles in ovarian development. Females homozygous for fused and either
      heterozygous or homozygous for the second chromosomal recessive gene female
      sterile (fes) were also studied. The fes gene was shown to be epistatic to fu in
      fu/fu; fes/fes females, and the rate of tumor production was greater in fu/fu;
      fes/+ females than in fu/fu; +/+ females. A mechanism for the action of fu and
      fes in controlling cell division is presented.

PMID- 18630321
TI  - Effects of ribonuclease and deoxyribonuclease on a murine leukemia virus
      (Rauscher).
AB  - Plasma pellets and femoral bone marrow from BALB/cJ mice infected with the
      Rauscher leukemia virus were fixed, embedded, and sectioned. The thin sections
      were incubated in ribonuclease and deoxyribonuclease solutions, stained, and
      examined in the electron microscope. Specific attention was paid to the action of
      the nucleases on characteristic virus particles in the plasma preparations and on
      viruses being produced by the "budding" phenomenon in the femoral bone marrow.
      Ribonuclease solutions digested the nucleoids of the virus particles in the
      plasma preparations from mice infected with Rauscher leukemia virus. The nucleoid
      portion of the "budding" virus particles in bone marrow, and the connecting
      cytoplasm of the stalks were also digested by ribonuclease solutions. In
      addition, the outer coat of the "budding" particles was affected in a nonspecific
      manner. The centers of the "budding" particles in the bone marrow and the
      nucleoids of viruses in plasma preparations were not digested by
      deoxyribonuclease solutions. Influenza virus, a known ribonucleic acid (RNA)
      virus, was used as a control for nuclease activity. The nucleoids of influenza
      virus particles were digested by ribonuclease but not by deoxyribonuclease
      solutions. After coriphosphine staining of the plasma virus preparations, the
      fluorescence was quenched in preparations treated with ribonuclease, but did not
      appear to be diminished in those treated with deoxyribonuclease. This study
      suggests that infection of mice with Rauscher leukemia virus produces virus
      particles in plasma and "budding" particles in bone marrow, both of which contain
      RNA.

PMID- 18630322
TI  - Spontaneous, malignant transformation of hamster embryo cells in vitro.
AB  - Primary hamster-embryo cells were dispersed in vitro. The frequency of colony
      development depended on the original method used for dispersing the cells and on
      the number of cells seeded. Cell populations derived from passages in vitro of 3
      colony isolates produced tumors when inoculated into baby or adult hamsters.
      Similar populations derived from primary or confluent, passaged cell cultures
      failed to produce tumors. The transformed cells were long, parallel Fibroblasts
      or short, randomly arranged spindle types. It is suggested that malignant,
      spontaneous transformation of cells occurs within a limited number of passages in
      vitro and that these cells may be a factor in virus-induced cell transformations.

PMID- 18630323
TI  - Carcinogenic effects of intragastric 3-methylcholanthrene and 7,12
      dimethylbenz[a]anthracene in Wistar and Sprague-Dawley rats.
AB  - In 2 experiments involving 384 rats of the Wistar (W) and Sprague-Dawley (SD)
      strains, the carcinogenic effects of repeated intragastric instillations of 3
      methylcholanthrene (MCA) were compared with those of single intragastric doses of
      7,12-dimethylbenz[a]anthracene (DMBA). Mammary carcinomas appeared in a higher
      proportion and earlier in SD than in W rats exposed to either carcinogen (during
      36 weeks, 90 vs. 50% with MCA in SD and W rats, at an average of 12 and 15 weeks,
      respectively, and 80 vs. 64% with DMBA in SD and W rats, at an average of 16 and
      22 weeks, respectively). Fibroadenomas of the breast were seen in 20 percent of
      SD rats by 36 weeks. In W rats observed for 1 year following DMBA administration,
      Fibroadenomas occurred in 64 percent and adenosis in 49 percent, at an average of
      45 to 51 weeks, whereas after MCA administration these reactions occurred in less
      than 10 percent. Intraluminal secretion indicative of lactation was noted in
      approximately 20 percent of fibroadenomas and adenoses. Nine W rats developed
      lymphoma, 5 following DMBA and 4 following MCA administration. Uterine papillary
      formations were observed in 1 W and 2 SD rats, and uterine carcinomas in 2 SD
      rats; 3 animals had received DMBA and 2, MCA.

PMID- 18630324
TI  - An epithelioid variant of the BHK21 hamster fibroblast line and its
      transformation by polyoma virus.
AB  - An epithelioid variant, which forms characteristic colonies in soft agar medium,
      has been isolated from the BHK21/13 line of hamster fibroblasts. After infection
      with a high multiplicity of polyoma virus, a fraction of the cells is
      morphologically transformed. Transformation may be demonstrated in two ways: 1)
      When infected cells are grown on glass, dense colonies of transformed cells
      develop from the confluent monolayer of untransformed cells in which
      multiplication has stopped because of their contiguity. 2) In agar, colonies
      derived from transformed cells are larger and morphologically distinct from those
      formed by the untransformed cells. The variant cells produce tumors in hamsters.
      Their transplantability is increased by polyoma transformation. Transformed cells
      possess a new polyoma-specific cell antigen.

PMID- 18630325
TI  - Neonatal thymectomy and tumor induction with methylcholanthrene in mice.
AB  - Methylcholanthrene was administered intradermally to adult normal and neonatally
      thymectomized mice. The incidence, latency period, growth rate, and histological
      type of the developing tumors were not significantly different for thymectomized
      mice as compared with those for controls. The antigenicity of the tumors varied
      in both groups, but the percentage of strongly antigenic tumors was unequivocally
      higher in thymectomized mice. Other investigators demonstrated a clearly
      increased susceptibility of thymectomized rodents to the carcinogenic effect of
      benzopyrene and to certain tumor viruses. They postulated that an enhanced
      incidence of the mostly antigenic tumors is related to the impairment of immune
      reactivity after early thymectomy. To test this hypothesis, we determined the
      immune reactivity of each individual thymectomized mouse by grafting homologous
      skin before administering the carcinogen. Thymectomized mice with normal
      homograft reactivity were thus distinguishable from those with depressed
      reactivity. Surprisingly, tumor incidence in the latter group was, if anything,
      lower than in the immunologically competent animals. It is plausible that
      immunological depression as a consequence of thymectomy promotes the
      establishment of antigenic tumors; on the other hand, the growth conditions for
      tumors, particularly for the less antigenic variety, may not be ideal in
      thymectomized mice.

PMID- 18630326
TI  - Growth of a human carcinoma of the cervix in mice thymectomized at birth.
AB  - Two-week-old neonatally thymectomized CBA mice were given subcutaneous injections
      of a suspension of 1 x 10(6) human cervical carcinoma cells that had been
      maintained in vitro for 3 years. Most of these mice developed solid tumors
      morphologically similar to the original carcinoma. A control group of normal mice
      given injections of similar cell suspensions did not develop tumors. The solid
      tumors growing from the cell suspensions were readily transplantable in
      neonatally thymectomized mice. The ease with which solid tumors arose from cells
      in suspension probably reflects the markedly defective homograft response of
      neonatally thymectomized mice. Such animals may serve as a useful model for
      further studies of the growth characteristics of human tumors in vivo.

PMID- 18630327
TI  - Forssman antigen content of guinea pig hepatomas induced by diethylnitrosamine: a
      quantitative approach to the search for tumor-specific antibodies.
AB  - The Forssman antigen content of diethylnitrosamine-induced guinea pig hepatomas
      was found to be greater than that of either autogenous or allogeneic guinea pig
      liver. The autogenous normal liver was obtained from guinea pigs before tumor
      induction, and comparison of normal and neoplastic tissues was based on the
      capacity of these tissues to inhibit (absorb) the hemolytic activity of rabbit
      antitumor serum. A method is presented for distinguishing quantitative from
      qualitative antigenic differences in the search for tumor-specific antigens. The
      results of these experiments indicate that, in the absence of strict
      quantitation, quantitative differences may be mistaken for qualitative
      differences.

PMID- 18630328
TI  - Chromosome abnormalities as primary events in human malignant disease: evidence
      from marker chromosomes.
AB  - Observations on the chromosomes of cells from 5 human malignant tumors are
      reported. Each tumor had one or more distinctive marker chromosomes. Marker
      chromosomes were present in a total of 700 of 711 metaphases from these tumors,
      which included an early malignant lesion of the cervix showing minimal invasion.
      Two tumors (a Stage 4 carcinoma of the cervix and a reticulum cell sarcoma, both
      untreated) yielded preparations of high quality. The 7 best-spread metaphases
      from the former with the modal number of chromosomes (60) had identical
      karyotypes, as did 16 from the latter with the modal number of 49. Less extensive
      data on 13 other tumors, 8 of which had marker chromosomes, are also presented.
      The data presented here, together with the published data on the chromosomes of
      cells from human tumors, support the view that human malignant tumors frequently
      but not invariably arise from a single cell in which chromosome changes have
      occurred. A carcinoma of the corpus uteri, to which brief reference is made, is a
      possible exception: Most metaphases had apparently normal karyotypes. The role of
      chromosome abnormalities (particularly structural changes) in the malignant
      transformation is discussed. Possible parallels between the chromosome findings
      in the cells of malignant tumors and those in chronic myeloid leukemia are
      considered. It is suggested that in tumors there may be both specific changes
      (perhaps involving chromosomes structurally changed) and coincidental changes.
      Variation in the coincidental changes might largely account for the wide
      differences between the karyotypes of different tumors.

PMID- 18630329
TI  - Immune cytolysis measurement by electrolytic conductance: preliminary note.

PMID- 18630330
TI  - [The solitary, benign cecal ulcer].

PMID- 18630331
TI  - [Isolated biventricular non-compaction cardimyopathy].

PMID- 18630332
TI  - [Young athlete patient with generalized swelling].

PMID- 18630333
TI  - Bibliography. Current world literature. Dermatology.

PMID- 18630334
TI  - Bibliography. Current world literature. Endocrinology and metabolism.

PMID- 18630338
TI  - Re: The efficacy of dihydrotestosterone transdermal gel before primary
      hypospadias surgery: a prospective, controlled, randomized study.

PMID- 18630339
TI  - Health situation remains grave in southern Sudan.

PMID- 18630340
TI  - Is the future Dutch?

PMID- 18630341
TI  - Who killed Cockrobin? The limitations of pathobiography.

PMID- 18630342
TI  - Recent publications in hematological oncology.

PMID- 18630343
TI  - Gas chromatography-mass spectrometry (GC-MS) method for the determination of 16
      European priority polycyclic aromatic hydrocarbons in smoked meat products and
      edible oils.
AB  - A gas chromatography-mass spectrometry (GC-MS) method was developed for the
      analysis of 15 polycyclic aromatic hydrocarbons (PAHs) highlighted as
      carcinogenic by the Scientific Committee on Food (SCF) plus benzo[c]fluorine
      (recommended to be analysed by the Joint FAO/WHO Expert Committee on Food
      Additives (JECFA) in fat-containing foods such as edible oils and smoked meat
      products. This method includes accelerated solvent extraction (ASE) and the
      highly automated clean-up steps gel permeation chromatography (GPC) and solid
      phase extraction (SPE). Using a VF-17ms GC column, a good separation of
      benzo[b]fluoranthene, benzo[j]fluoranthene and benzo[k]fluoranthene was achieved.
      Futhermore, the six methylchrysene isomers and the PAH compounds with a molecular
      weight of 302 Daltons in fat-containing foods attained a better chromatographic
      separation in comparison with a 5-ms column. The reliability of the analytical
      method for edible oils was demonstrated by the results from a proficiency test.
      Measurements with GC-high-resolution mass spectroscopy (HRMS) and gas
      chromatography-mass selective detection (GC-MSD) led to comparable results. A
      survey of the 16 PAHs in 22 smoked meat products showed concentrations in the
      range < 0.01-19 microg kg(-1). The median concentration for benzo[a]pyrene was
      below 0.15 microg kg(-1).

PMID- 18630344
TI  - A Sinorhizobium meliloti osmosensory two-component system required for cyclic
      glucan export and symbiosis.
AB  - screen for novel symbiotic mutants of the nitrogen-fixing legume symbiont
      Sinorhizobium meliloti uncovered a crucial role for the putative response
      regulator FeuP in the symbiotic infection process. Transcriptome analysis shows
      that FeuP controls the transcription of at least 16 genes, including ndvA, which
      encodes an ATP-dependent exporter of cyclic beta glucans. Loss of feuP function
      gives rise to traits associated with cyclic beta glucan biosynthetic defects,
      including poor growth and motility under hypoosmotic conditions, and the
      inability to invade plant tissue during the early stages of symbiotic infection.
      Analysis of cyclic glucans indicates that the feuP mutant is able to synthesize
      intracellular cyclic beta glucans, but is unable to export them. Cyclic beta
      glucan export can be restored to feuP mutant cells by constitutive expression of
      ndvA; likewise, the symbiotic phenotype of a feuP mutant is rescued by ectopic
      ndvA expression. We further show that the linked sensor kinase gene, feuQ, is
      also important for modulating ndvA transcription, and that signalling through the
      FeuP/FeuQ pathway is responsive to extracellular osmotic conditions, with low
      osmolarity stimulating ndvA expression.

PMID- 18630345
TI  - Interaction of quorum signals with outer membrane lipids: insights into
      prokaryotic membrane vesicle formation.
AB  - Bacteria have evolved elaborate communication strategies to co-ordinate their
      group activities, a process termed quorum sensing (QS). Pseudomonas aeruginosa is
      an opportunistic pathogen that utilizes QS for diverse activities, including
      disease pathogenesis. P. aeruginosa has evolved a novel communication system in
      which the signal molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas Quinolone
      Signal, PQS) is trafficked between cells via membrane vesicles (MVs). Not only is
      PQS packaged into MVs, it is required for MV formation. Although MVs are involved
      in important biological processes aside from signalling, the molecular mechanism
      of MV formation is unknown. To provide insight into the molecular mechanism of MV
      formation, we examined the interaction of PQS with bacterial lipids. Here, we
      show that PQS interacts strongly with the acyl chains and 4'-phosphate of
      bacterial lipopolysaccharide (LPS). Using PQS derivatives, we demonstrate that
      the alkyl side-chain and third position hydroxyl of PQS are critical for these
      interactions. Finally, we show that PQS stimulated purified LPS to form liposome
      like structures. These studies provide molecular insight into P. aeruginosa MV
      formation and demonstrate that quorum signals serve important non-signalling
      functions.

PMID- 18630346
TI  - A role for Lon protease in the control of the acid resistance genes of
      Escherichia coli.
AB  - Lon protease is a major protease in cellular protein quality control, but also
      plays an important regulatory role by degrading various naturally unstable
      regulators. Here, we traced additional such regulators by identifying regulons
      with co-ordinately altered expression in a lon mutant by genome-wide
      transcriptional profiling. Besides many members of the RcsA regulon (which
      validates our approach as RcsA is a known Lon substrate), many genes of the
      sigmaS-dependent general stress response were upregulated in the lon mutant.
      However, the lon mutation did not affect sigmaS levels nor sigmaS activity in
      general, suggesting specific effects of Lon on secondary regulators involved in
      the control of subsets of sigmaS-controlled genes. Lon-affected genes also
      included the major acid resistance genes (gadA, gadBC, gadE, hdeAB and hdeD),
      which led to the discovery that the essential acid resistance regulator GadE
      (whose expression is sigmaS-controlled) is degraded in vivo in a Lon-dependent
      manner. GadE proteolysis is constitutive as it was observed even under conditions
      that induce the system (i.e. at low pH or during entry into stationary phase).
      GadE degradation was found to rapidly terminate the acid resistance response upon
      shift back to neutral pH and to avoid overexpression of acid resistance genes in
      stationary phase.

PMID- 18630348
TI  - Sitaxentan: new drug. Pulmonary hypertension: better to continue to use bosentan.

PMID- 18630347
TI  - Repression of motility during fimbrial expression: identification of 14 mrpJ gene
      paralogues in Proteus mirabilis.
AB  - Proteus mirabilis alternates between motile and adherent forms. MrpJ, a
      transcriptional regulator previously reported to repress motility, is encoded at
      the 3' end of the mrp fimbrial operon in P. mirabilis. Sequencing of the P.
      mirabilis genome revealed 14 additional paralogues of mrpJ, 10 of which are
      associated with fimbrial operons. Twelve of these genes, when overexpressed,
      repressed motility; several distinct patterns of swarming motility were noted.
      Expression of 10 of the 14 mrpJ paralogues repressed flagellin (FlaA) synthesis.
      Alignment of the predicted amino acid sequences of MrpJ and its 14 paralogues
      revealed a conserved consensus motif (SQQQFSRYE) within the helix-turn-helix
      domain. Site-directed mutagenesis of these residues coupled with linker insertion
      mutagenesis of MrpJ confirmed the importance of this domain for repression of
      motility. Gel shift assays demonstrated that MrpJ and another paralogue UcaJ bind
      directly to the promoter region of the flagellar master regulator flhDC. Thus, P.
      mirabilis appears to use a related mechanism to inhibit motility during the
      production of at least 10 of its predicted fimbriae.

PMID- 18630349
TI  - Retraction notice to "Preconcentration and solid phase extraction method for the
      determination of Co, Cu, Ni, Zn and Cd in environmental and biological samples
      using activated carbon by FAAS". [J. Hazard. Mater. 147 (1/2) (2007) 15-20].

PMID- 18630350
TI  - Nuclear receptor-enhanced transcription requires motor- and LSD1-dependent gene
      networking in interchromatin granules.

PMID- 18630351
TI  - Idursulfase: a poor risk-benefit balance in type II mucopolysaccharidosis.
AB  - Weekly infusions of idursulfase have no tangible benefit in boys with type II
      mucopolysaccharidosis who already have respiratory involvement, while
      hypersensitivity reactions are frequent and sometimes serious. Idursulfase should
      only be given to infants if they are enrolled in clinical trials.

PMID- 18630352
TI  - Sevelamer: constipation and occlusion. Complications, sometimes fatal.

PMID- 18630354
TI  - Botulinum toxin: risk of death. Beware muscle symptoms.

PMID- 18630353
TI  - Exenatide: pancreatitis. Watch out for nausea and vomiting.

PMID- 18630355
TI  - Tegaserod: withdrawal from the world market. A treatment for constipation with
      cardiovascular adverse effects.

PMID- 18630356
TI  - Clobutinol: severe cardiac arrhythmias. Old drugs should also be monitored.

PMID- 18630357
TI  - Donepezil: syncope. Various cardiac disorders.

PMID- 18630358
TI  - Entacapone: hepatitis (continued). The risk of liver damage is being confirmed.
      It is better not to expose parkinsonian patients to this drug.

PMID- 18630359
TI  - Continuing where grandmother left off.

PMID- 18630360
TI  - Postpartum wrapping ceremony clarified.

PMID- 18630362
TI  - Labs are vital.com. Facebook initiative motivates students to consider lab
      careers.

PMID- 18630361
TI  - Reuse of needles in Nevada.

PMID- 18630363
TI  - Measles vaccine.

PMID- 18630364
TI  - Creating panic during disasters.

PMID- 18630365
TI  - The limits of choice.

PMID- 18630366
TI  - Unethical restriction of kidney transplantation.

PMID- 18630367
TI  - Skeptical of political studies.

PMID- 18630368
TI  - Scientific correction.

PMID- 18630369
TI  - Thanks MSMA! Missouri M-one.

PMID- 18630370
TI  - What to expect from diabetes education.

PMID- 18630371
TI  - Diabetes and bone health.

PMID- 18630372
TI  - Diabetes basics. Keeping your eyes healthy.

PMID- 18630373
TI  - Fast-food cooking at home. Burgers and sides.

PMID- 18630374
TI  - When Viagra doesn't work. Treating erectile dysfunction.

PMID- 18630375
TI  - Calories. The key to weight control.

PMID- 18630376
TI  - Yoga. Uniting body, mind, and spirit.

PMID- 18630377
TI  - For parents. Community solutions to childhood obesity.

PMID- 18630378
TI  - Diabetes resources. Finding peer support.

PMID- 18630379
TI  - Supermarket smarts. Fresh, frozen, and canned poultry.

PMID- 18630380
TI  - Diabetes quiz. How much do you know about carbohydrate?

PMID- 18630381
TI  - The volume and structure of the transatlantic slave trade: a reassessment.

PMID- 18630382
TI  - [The limitations of worker technical education in Spain under Isabella II: the
      Bejar industrial school, 1852-67].

PMID- 18630384
TI  - The cattle plague in Cheshire, 1865-1866.

PMID- 18630383
TI  - [The other Cuba: white colonization and agricultural diversification].

PMID- 18630385
TI  - Witches and missionaries in nineteenth century Transvaal.

PMID- 18630386
TI  - Bibliography. Current world literature. Facial plastic surgery.

PMID- 18630387
TI  - The costs of coercion: African agency in the pre-modern Atlantic world.

PMID- 18630388
TI  - Arterial hypertension: second-line treatment. Try other single-agent treatments.
AB  - (1) Reliable evidence supports the use of thiazide diuretics (chlortalidone or
      hydrochlorothiazide) as first-line treatment for uncomplicated arterial
      hypertension. (2) When patients fail to reach blood pressure targets with well
      conducted treatment with thiazide diuretics, or this treatment is poorly
      tolerated, what are the best second-line options? To answer this question, we
      reviewed the available evidence, based on our standard in-house methodology. (3)
      We found no published trials specifically designed to evaluate second-line
      antihypertensive treatments in cardiovascular prevention. There were no available
      trials of dual- versus single-agent therapy after failure of a thiazide diuretic.
      (4) When the blood pressure target is not reached, inadequate drug efficacy is
      only one of several possible causes. Various other factors affecting blood
      pressure should also be investigated. (5) Dual-agent therapy carries an increased
      risk of adverse effects and drug interactions compared to monotherapy. (6) There
      is no consensus among clinical practice guidelines on second-line
      antihypertensive therapy. However, to minimise the risk of adverse effects, it is
      clearly better to select single-agent therapy with a drug that has been shown to
      prevent cardiovascular events in first-line treatment of otherwise healthy
      hypertensive patients. Possible options include: angiotensin-converting-enzyme
      inhibitors, angiotensin II antagonists, calcium channel blockers or betablockers.
      In patients over the age of 60, betablockers seem less effective that the other
      drugs in preventing strokes. (7) There is too little evidence to choose a
      specific third-line combination rather than another. However, any adverse effects
      that the patient experienced during prior treatments should be taken into
      account.

PMID- 18630389
TI  - Diabetes and alcohol: distinctive interactions.
AB  - (1) Many diabetic patients, like the rest of the population, enjoy alcoholic
      drinks. We conducted a review of the literature for information on the possible
      risks of alcohol consumption for diabetic patients, based on our standard in
      house methodology. (2) Many of the data we found are not very convincing, because
      alcohol consumption was not properly taken into account. Nevertheless, they
      provide some useful pointers for diabetic patients. (3) Most wines and spirits do
      not contain sugar. However, some alcoholic beverages contain sugar and can affect
      glycaemic control. (4) Light consumption of alcohol seems to have a favourable
      effect on the vascular complications of diabetes. Drinking one standard unit a
      day (about 10 grams of alcohol) seems to be an acceptable amount. (5) Alcohol
      consumption can cause episodes of severe hypoglycaemia in diabetic patients,
      sometimes occurring several hours later. Fasting, sustained physical exercise and
      malnutrition are precipitating factors. (6) Alcohol can provoke ketoacidosis,
      which should not be confused with diabetic ketoacidosis. Alcoholic ketoacidosis
      requires rehydration but not insulin. (7) Studies of alcohol withdrawal in
      patients with peripheral and vegetative neuropathies, severe foot lesions,
      erectile disorders, liver disease or depression have provided conflicting
      results. However, in practice, it seems better to recommend abstinence in
      patients with these conditions, as alcohol is an aggravating factor.

PMID- 18630392
TI  - [Classification of the cardiomyopathies].

PMID- 18630390
TI  - Herbal remedies for dyspepsia: peppermint seems effective.
AB  - (1) Functional dyspepsia is extremely common, yet few if any treatments have been
      shown to be effective. This review examines the potential benefits and risks of
      using herbal products in treating symptoms of dyspepsia. (2) About forty plants
      have been approved in France in the composition of products traditionally used
      for dyspepsia. (3) The clinical efficacy of most of these plants has not been
      assessed. Some essential oils can cause severe adverse effects, including
      seizures. Herbal teas appear to be safe when used appropriately. (4) A few
      randomised controlled clinical trials suggest that peppermint essential oil is
      effective in reducing abdominal pain, flatulence and diarrhea in patients with
      "irritable bowel syndrome". Peppermint tea, containing essential oil, has no
      known adverse effects. (5) There is no sound reason to discourage patients from
      using herbal teas made from plants such as lemon balm, German chamomile or star
      anise.

PMID- 18630398
TI  - [Report from China Interventional Therapeutics 2008, Beijing, China 19
      23.03.2008].

PMID- 18630391
TI  - Treatment of gout attacks.
AB  - Gout attacks resolve in 3 to 10 days without treatment. Treatment is mainly
      empirical. Paracetamol and application of ice can be tried. If they fail, the
      best options is a moderate dose of ibuprofen, and NSAID with well-documented
      adverse effects.

PMID- 18630393
TI  - Youth violence. Scientific approaches to prevention. Prologue.

PMID- 18630400
TI  - Developing health system surge capacity: community efforts in jeopardy.
AB  - Since Sept. 11, 2001, communities have responded to the federal call to enhance
      health care surge capacity--the space, supplies, staffing and management
      structure to care for many injured or ill people during a terrorist attack,
      natural disaster or infectious disease pandemic. Communities with varied
      experience handling emergencies are building broad surge capacity, including
      transportation, communication, hospital care and handling mass fatalities,
      according to a new study by the Center for Studying Health System Change (HSC).
      Communities rely on federal funding to help coordinate and plan across agencies
      and providers, conduct training and drills, recruit volunteers, and purchase
      equipment and stockpile supplies. The current federal focus on pandemic influenza
      has helped prepare for all types of emergencies, although at times communities
      struggle with fragmented and restrictive funding requirements. Despite progress,
      communities face an inherent tension in developing surge capacity. The need for
      surge capacity has increased at the same time that daily health care capacity has
      become strained, largely because of workforce shortages, reimbursement pressures
      and growing numbers of uninsured people. Payers do not subsidize hospitals to
      keep beds empty for an emergency, nor is it practical for trained staff to sit
      idle until a disaster hits. To compensate, communities are trying to develop
      surge capacity in a manner that supports day-to-day activities and stretches
      existing resources in an emergency. Many of these efforts--including integrating
      outpatient providers, expanding staff roles and adapting standards of care during
      a large-scale emergency--require greater coordination, guidance and policy
      support. As time passes since 9/11 and Hurricane Katrina, federal funding for
      surge capacity has waned, and communities are concerned about losing surge
      capacity they have built.

PMID- 18630402
TI  - Getting what we pay for: innovations lacking in provider payment reform for
      chronic disease care.
AB  - Despite wide recognition that existing physician and hospital payment methods
      used by health plans and other payers do not foster high-quality and efficient
      care for people with chronic conditions, little innovation in provider payment
      strategies is occurring, according to a new study by the Center for Studying
      Health System Change (HSC) commissioned by the California HealthCare Foundation.
      This is particularly disconcerting because the nation faces an increasing
      prevalence of chronic disease, resulting in continued escalation of related
      health care costs and diminished quality of life for more Americans. To date,
      most efforts to improve care of patients with chronic conditions have focused on
      paying vendors, such as disease management firms, to intervene with patients or
      redesigning care delivery without reforming underlying physician and hospital
      payment methods. While there is active discussion and anticipation of physician
      and hospital payment reform, current efforts are limited largely to experimental
      or small-scale pilot programs. More fundamental payment reform efforts in
      practice are virtually nonexistent. Existing payment systems, primarily fee for
      service, encourage a piecemeal approach to care delivery rather than a
      coordinated approach appropriate for patients with chronic conditions. While
      there is broad agreement that existing provider payment methods are not well
      aligned with optimal chronic disease care, there are significant barriers to
      reforming payment for chronic disease care, including: (1) fragmented care
      delivery; (2) lack of payment for non-physician providers and services supportive
      of chronic disease care; (3) potential for revenue reductions for some providers;
      and (4) lack of a viable reform champion. Absent such reform, however, efforts to
      improve the quality and efficiency of care for chronically ill patients are
      likely to be of limited success.

PMID- 18630394
TI  - Polish Forum for Prevention Guidelines on overweight and obesity.

PMID- 18630396
TI  - [Commentary to the article: Kastelein JJ, Akdim F, Stroes ES, et al.; ENHANCE
      Investigators. Simvastatin with or without ezetimibe in familial
      hypercholesterolemia. N Engl J Med 2008; 358: 1431-43 ].

PMID- 18630397
TI  - [The illness and death of heir to the throne Nikolai Aleksandrovich].

PMID- 18630403
TI  - [Psychophysiological analysis of condition reflex nature specificity of oral
      cavity perceptogenesis and connected with it problems of practical stomatology].

PMID- 18630395
TI  - [Ethnic and vocational identity: a group of immigrants and their descendants,
      1741-1865].

PMID- 18630399
TI  - The French slave trade: an overview.

PMID- 18630401
TI  - Mortality and voyage length in the middle passage revisited.

PMID- 18630406
TI  - [Improvement of surgical treatment of mandible chronic traumatic osteomyelitis].

PMID- 18630407
TI  - [Post doctorate studies in the United States: experiences as a post doctoral
      student of nursing sciences in the USA].

PMID- 18630404
TI  - [Oral cavity as local ecological system].

PMID- 18630408
TI  - [Metabolic syndrome in the elderly].

PMID- 18630409
TI  - [Perspective of centenarians study 2].

PMID- 18630410
TI  - William John Gies Award.

PMID- 18630411
TI  - Survey: wired hospitals embrace electronic medical records.

PMID- 18630412
TI  - Collaboration aspires to accelerate digitization of patient records.

PMID- 18630405
TI  - [Oral cavity microflora's role in human diseases development].

PMID- 18630414
TI  - Working side by side... Joint procedures help unite IS and biomed departments.

PMID- 18630413
TI  - Medical test on CD delivers good results--fast.

PMID- 18630416
TI  - Protecting networked medical devices from worms and viruses.

PMID- 18630415
TI  - Logging on: what it takes to provide patients with computer access.

PMID- 18630417
TI  - Boosting a field engineer's productivity with mobile solutions.

PMID- 18630418
TI  - The next medical revolution--health information technology.

PMID- 18630423
TI  - Using IT tools to support online clinical training.

PMID- 18630426
TI  - [Treatment evaluation of distal femoral fracture by less invasive stabilization
      system via two incisions].
AB  - OBJECTIVE: To evaluate the clinical results of less invasive stabilization system
      (LISS) for femur supracondylar and intercondylar fractures. METHODS: From March
      2004 to November 2005, 47 patients with 49 intercondylar and supracondylar
      fractures were treated. Of all the patients, there were 34 males and 13 females
      with an average of 39.7 years (range 19-56 years). The locations were left side
      in 21 cases and right side in 28 cases. Fracture was caused by traffic accident
      in 31 cases, falling in 8 cases, violence in 6 cases and others in 2 cases. Forty
      nine fractures included 14 intercondylar fractures, 21 supracondylar fractures
      and 14 intercondylar and supracondylar fractures; 32 closed fractures and 17 open
      fractures. According to the AO typing, there were 6 type 33-A1, 8 type 33-A2, 10
      type 33-A3, 7 type 33-C1, 3 type 33-C2 and 15 type 33-C3. The disease course was
      30 minutes to 6 days. Articular surface reduction was first performed, then the
      LISS plate was inserted via two incisions and locking screws were used later.
      RESULTS: The average operation time was 126 minutes (range 48-248 minutes). The
      blood loss was 180 mL (range 60-1,200 mL). The average follow-up time was 18.6
      months (range 12-23 months). There were 4 patients with AP angular deformity and
      5 patients with lateral angular deformity (range 2-5 degrees). External rotation
      deformity was presented in 2 patients. There were no plate breakage, screw loosen
      and fixation failure. Average bone union time was 5.6 months (range 3-8 months)
      without infection case. Six cases were treated with iliac bone transplantation
      for delayed union. CONCLUSION: LISS is one kind of effective treatment to femoral
      intercondylar and supracondylar fractures.

PMID- 18630421
TI  - From a vendor's viewpoint... Providing IT support and how you can help.

PMID- 18630419
TI  - How wireless LANs can enhance the clinical environment.
AB  - WLANs deployments in health care institutions offer clinicians opportunities to
      increase productivity and improve patient care with additional point-of-care
      access to information systems. However, they are not a panacea. Any data that
      needs guaranteed reliability and protection for outside interference, such as
      real-time cardiac monitoring, should be on networks operating in the Wireless
      Medical Telemetry Service (WMTS) range. The WMTS range, (608-614 MHz, 1395-1400
      MHz, and 1429-1432 MHz), was established in 1999 by the FCC as a protected
      frequency range (in the U.S.) making these products less likely to have
      interference problems than devices operating in the 802.11 range. Security
      challenges must also be addressed as each access point is synonymous with
      installing a RJ45 network jack in the parking lot of a facility and inviting the
      general public to connect to a network. Also, increased mobility of electronic
      devices means battery power; thus consideration will need to be given to
      charging, maintaining, and disposal of batteries. WLANs offer many advantages
      over conventional wired LANs but they also offer many challenges in addressing
      security and reliability issues. WLANs are not designed to replace conventional
      hard-wired network infrastructure; they are designed to augment the connectivity
      of LANs. Even with the 802.11 g standard, which supports connectivity up to 54
      Mbps, large medical image files would not have enough bandwidth on this type of
      wireless network. Wireless networks can enhance the health care technology
      infrastructure but proper selection of technology and focus on the security and
      reliability during the planning and installation is a definite requirement.

PMID- 18630422
TI  - The ingredients to IT training: what biomeds need to know.

PMID- 18630420
TI  - Patient monitoring on local area networks... Considerations for building a
      network.

PMID- 18630425
TI  - [A biomechanical study on internal and external fixation devices for treatment of
      humeral shaft fracture].
AB  - OBJECTIVE: To provide the scientific theoretical basis for clinical practice by
      comparing biomechanical characteristics of single compressed plate with
      intramedullary pin, locking intramedullary nail and simple arm external fixator
      with simple internal fixation devices. METHODS: Eighteen wet humeral bone
      specimens of adult cadaver were made complicated fracture models of humeral shaft
      and divided into 3 groups according to fixation methods. Fracture was fixed by
      single compressed plate with intramedullary pin in plate group, by locking
      intramedullary nail in intramedullary nail group and by external fixator with
      simple internal fixation devices in external fixator group. The intensity and
      rigidity of complicated fracture models of humeral shaft was measured in compress
      test and torsion test. RESULTS: In compress test, the maximum load in plate group
      (6,162.09 +/- 521.06) N and in intramedullary nail group (6,738.32 +/- 525.89) N
      was significantly larger than that in external fixator group (2,753.57 +/-
      185.59) N (P < 0.05); but there was no significant difference between plate group
      and intramedullary nail group (P > 0.05). Under 600 N physiological compress
      load, the rigidity was (171.69 +/- 6.49) N/mm in plate group, (333.04 +/- 36.85)
      N/mm in intramedullary nail group and (132.59 +/- 2.93) N/mm in external fixator
      group; showing no significant difference between plate group and external fixator
      group (P > 0.05), and showing significant difference between intramedullary nail
      group and plate, external fixator groups (P < 0.05). In torsion test, the maximum
      torque in plate group (38.24 +/- 7.08) Nm was significantly larger than those in
      intramedullary nail group (17.12 +/- 5.73) Nm and external fixator group (20.26
      +/- 6.42) Nm (P < 0.05), but there was no significant difference between
      intramedullary nail group and external fixator group (P > 0.05). Under 0.80 Nm
      physiological torque, the rigidity was (16.36 +/- 2.07) Ncm/degree in plate group
      and (18.79 +/- 2.62) Ncm/degree in external fixator group, which was
      significantly larger than that in intramedullary nail group (11.45 +/- 0.22)
      Ncm/degree (P < 0.05); but there was no significant difference between plate
      group and external fixator group (P > 0.05). CONCLUSION: Those fracture models
      fixed by single compressed plate with intramedullary pin have better compress and
      torsion intensity, they also have better torsion rigidity but less compress
      rigidity. Those fracture models fixed by locking intramedullary nail have better
      compress intensity but less torsion intensity, they also have better compress
      rigidity but less torsion rigidity. Those fracture models fixed by external
      fixator with simple internal fixation device have less compress and torsion
      intensity, they also have less compress rigidity but better torsion rigidity.

PMID- 18630427
TI  - [Study on shape and structure of calcified cartilage zone in normal human knee
      joint].
AB  - OBJECTIVE: To explore the shape and structure of calcified cartilage zone and its
      interface between the non-calcified articular cartilage and subchondral bone
      plate. METHODS: The normal human condyles of femur (n=20) were obtained from the
      tissue bank donated by the residents, 10 males and 10 females, aged 17-45 years.
      The longitudinal and transverse paraffin sections were prepared by the routine
      method. The shape and structure of calcified cartilage zone were observed with
      the Safranin O/fast green and von kossa stain method. The interface conjunction
      among zones of cartilage was researched by SEM and the 3D structural model was
      established by serial sections and modeling technique. RESULTS: Articular bone
      cartilage safranin O/fast green staining showed that cartilage was stained red
      and subchondral bone was stained blue. The calcified cartilage zone was located
      between the tidemark and cement line. Von kossa staining showed that calcified
      cartilage zone was stained black and sharpness of structure border. Upper
      interface gomphosised tightly with the non-calcified cartilage by the wave shaped
      tidemark and lower interface anchored tightly with the subchondral bone by the
      uneven comb shaped cement line. The non-calcified cartilage zone was interlocked
      tightly in the manner of "ravine-engomphosis" by the calcified cartilage zone as
      observed under SEM, and the subchondral bone was anchored tightly in the manner
      of"comb-anchor" by the in the calcified cartilage zone 3D reconstruction model.
      CONCLUSION: The calcified cartilage zone is an important structure in the
      articular cartilage. The articular cartilage is fixed firmly into subchondral
      bone plate by the distinctive conjunct interfaces of calcified cartilage zone.

PMID- 18630428
TI  - [Effect of bone tunnel diameter on anterior cruciate ligament insertion outcome].
AB  - OBJECTIVE: To observe the histology change of the insertion using different
      diametrical bone tunnel in anterior cruciate ligament (ACL) reconstruction.
      METHODS: Ninety Japanese rabbits were selected, mihout female and male limit,
      weighing 2.5-3.0 kg, and were randomly divided into 3 groups, 30 in each group.
      The ratio of transplantation ligament diameter and bone tunnel diameter was 1/1
      (group A), the ratio was 1/1.5 (group B), and the ratio was 1/2 (group C). Bone
      tunnel observation and histology observation were carried out in the 4th, 8th and
      16th weeks postoperatively. RESULTS: Wound healed well in 3 groups. The mean time
      of walking functional recovery was 1.5, 2.0 and 3.5 days in groups A, B and C
      respectively. After 4 weeks of operation, more soft tissues at tunnel entry were
      observed in group A and group B than in group C; after 8 weeks of operation,
      there was no crevice at bone-tunnel entry of the groups A and B, there was no
      improvement in group C; after 16 weeks of operation, groups A and B showed the
      normal insertion, group C had no normal insertion. Histology observation: in
      groups A, B and C, bone-tunnel was filled with loose connective tissue after 4
      weeks of operation; group A and group B emerged the discontinuation ACL insertion
      tidal line after 8 weeks of operation, group C had no insertion; groups A and B
      emerged the similarity normal ACL insertion tidal line structure after 16 weeks
      of operation, but group C had no this structure. The results of ultimate tensile
      strength in groups A, B and C were (75.44 +/- 7.06), (91.37 +/- 6.14) and (126.91
      +/- 4.61) N respectively at 4 weeks; the results were (74.31 +/- 4.81), (88.30 +/
      7.46) and (124.34+/- 8.44) N respectively at 8 weeks; and the results were
      (62.20 +/- 5.32), (71.53 +/- 5.99) and (83.62 +/- 5.69) N respectively at 16
      weeks. There was no significant difference between group A and group B (P >
      0.05), and there were significant differences between groups A, B and group C (P
      < 0.05). CONCLUSION: In the ACL reconstruction, the ratio of transplantation
      ligament diameter and bone tunnel diameter being 1/1.5 will not affect the
      insertion outcome, but if the ratio less than the limit it will affect the
      insertion outcome.

PMID- 18630430
TI  - [Internal fixation of spinal column by posterior approach and extraperitoneal
      bilateral focal debridement for treatment of tuberculosis of lumbosacral
      vertebral body].
AB  - OBJECTIVE: To evaluate the application value of internal fixation of spinal
      column by posterior approach and extraperitoneal bilateral focal debridement for
      the treatment of tuberculosis of lumbosacral vertebral body. METHODS: From March
      2000 to February 2005, 16 cases of spinal tuberculosis in L3-S1 were treated with
      internal fixation of spinal column by posterior approach and extraperitoneal
      bilateral focal debridement. Sixteen cases included 11 males and 5 females, and
      the age was 21-56 years. The locations of spinal tuberculosis were L3 in 4 cases,
      L4 in 6, Ls in 4, and S1 in 2. The course of disease averaged 13 months (range 6
      months to 6 years). The ESR of all cases was greater than 20 mm/h (average 40
      mm/h); WBC was normal in 14 cases, and a little high in 2 cases. The X-ray
      picture showed narrow intervertebral space in 5 cases, compressed body of
      vertebra in 7 cases, and destroyed 2 consecutive vertebra and its sclerotin was
      conduplicate in 1 case. All cases were abscess in major psoas muscle. The CT
      showed destruction of bone, abscess-formation and dead bone in body of vertebra
      of 16 cases. The abscess were found in vertebral canal in 5 cases and dura mater
      of spinal cord and spinal nerve root crushed in 2 cases. The MRI showed
      destruction of bone, abscess-formation and hibateral abscess in major psoas
      muscle in 11 cases. The abscess were found in vertebral canal and dura mater of
      spinal cord and spinal nerve root crushed in 6 cases. The therapy of paid was
      treated after operation in all the cases. RESULTS: Incision healed by first
      intention in 16 cases; and disruption of wound occurred and healing was achieved
      after symptomatic treatment in 1 case. Sixteen cases were followed up 2-5 years
      (29 months on average). Among all the cases, anaesthesia in double thigh was
      found in 3 cases, adynamia of dorsiflexion in foot in 1 case, gatism in 1 case;
      after 2 weeks the symptoms were vanished. Indirect hernia of fold inguen were
      found in 1 case after 2 years, and the patient refused operation for age and was
      no longer followed up. Fuzzy, ensic and acerb in eyes were found in 6 cases,
      hearing disturbance were found in 2 cases, and symptoms were vanished after
      medication adjustment. Low-grade fever and lumbar myalgia were found in 1 case
      and cured after staying in bed and medication adjustment. All ESR were normal,
      synostosis of lumbosacral vertebral body was found in 13 cases, kyphosis in 1
      case. CONCLUSION: Internal fixation of spinal column by posterior approach and
      extraperitoneal bilateral focal debridement is safe and available way for the
      treatment of tuberculosis of lumbosacral vertebral body, it can save the times of
      operation, shorten period and enhance effect of treatment.

PMID- 18630424
TI  - [Treatment of mid-distal humeral shaft fractures associated with radial nerve
      palsy using minimally invasive plating osteosynthesis technique].
AB  - OBJECTIVE: To explore the possibility of treating mid-distal humeral shaft
      fractures associated with radial nerve palsies with minimal invasive plating
      osteosynthesis (MIPO) techniques. METHODS: From April 2003 to October 2006, 10
      patients with mid-distal humeral shaft fractures associated with radial nerve
      palsies were treated. All patients were male, aged 19-58 years. According to
      AO/ASIF classification, there were 4 cases of B1 type, 2 cases of B3 type, 1 case
      of A2 type, 1 case of B2 type, 1 case of C3 type and 1 case of A3 type. A
      straight 4.5 mm dynamic compression plate was placed on the anterior aspect of
      humerus through two small incisions located on the anterior side of proximal and
      distal part of the arm. The radial nerve exploration was performed through a
      lateral small incision made on the fracture site. The fractures were then reduced
      by manual manipulation and the plate was fixated to the main fragments with 3
      screws in each end of the plate. The postoperative complications, the bone
      healing time, and the recovery time of the radial nerve functions were recorded.
      The functions of the affected shoulder and elbow were assessed with UCLA and Mayo
      elbow performance score system respectively. RESULTS: All incision healed by
      first intention. Ten patients were followed up 9-36 months with an average of
      15.7 months. The X-ray films showed that the union of fractures was achieved 12
      16 weeks (13.6 weeks on average). The function of the radial nerves recovered
      completely 12-36 weeks (17.8 weeks on average) in 9 patients. The abductions of
      the affected shoulder were 150-170 degrees (165 degrees on average). The ROM of
      the elbows were 130-140 degrees (135.5 degrees on average). According to the UCLA
      shoulder scoring system, 9 patients achieved the excellent result and 1 patient
      achieved the good result. All the patients had the excellent results according to
      Mayo elbow performance score system. CONCLUSION: The mid-distal humeral shaft
      fractures associated with radial nerve palsies can be treated with MIPO technique
      and the good results can be obtained.

PMID- 18630433
TI  - [Following-up study on recovery of amputated foot after temporary ectopic
      implantation].
AB  - OBJECTIVE: To study the recovery method and effect of amputated foot after
      temporary ectopic implantation. METHODS: Two male patients with amputated foot
      were treated with temporary ectopic implantation in July 2001 and January 2002.
      Amputated foot was caused by mechanical injury and crush injury. After 6 hours,
      temporary ectopic implantation of amputated foot was given and replantation was
      done 3 months after primary operation. The recovery methods were as follows:
      automatic and passive motion, high pressure oxygen, massage, protective and
      positional feeling training, etc. The effects of recovery was observed. RESULTS:
      All amputated foots survived after operation, the time of follow-up was 6 years,
      and 5 years and 7 months. Extension degree of first metatarsal digital joint was
      12 degrees and 15 degrees, flex degree of first metatarsal digital joint was 15
      degrees and 13 degrees, and extension degree of other metatarsal digital joints
      was 8 degrees and 9 degrees. Force degree of extension muscle was 4, force degree
      of flex muscle was 4, and two-point discrimination was 20 mm and 18 mm. Patients
      recovered their superficial sensibility, touch sense, deep pain sense and
      topognosis. The skin color and temperature were normal. And the patients could do
      some housework. CONCLUSION: Temporary ectopic implantation of amputated foot can
      recover the function of amputated foot by motor and sensitive recovery methods.

PMID- 18630434
TI  - [Bridging effect of expansion prefabrication on crossing area supply axial
      pattern flap in pigs].
AB  - OBJECTIVE: To explore the effects of tissue expansion on the anastomoses and the
      survival of the axial pattern flap with a crossing area supply so as to improve
      the survival of crossing area axial pattern flap and to provide a new idea for
      the development of original crossing area axial flap. METHODS: The experiment
      included two parts. Experiment A was divided into expansion group and control
      group. Square flaps were randomly designed on own control bilaterally in each
      animal with a boundary of midline. Experiment B was divided into expansion group
      and delay group. The flaps were also randomly designed on own control
      bilaterally. Angiographic analysis and gross survival observation were carried
      on. RESULTS: Experiment A: Angiography showed that there were abundant
      anastomoses with big caliber between deep iliac circumflex artery and superior
      epigastric artery in expansion group and there were only 3-4 anastomoses in
      control group. Experiment B: Angiography showed that there were abundant
      anastomoses with big caliber in expansion group and there were two arterial
      systems with relatively less anastomoses and smaller caliber in delay group. The
      survival rates in expansion group was significantly higher than that in the
      control group (90.16% +/- 3.61% vs 72.67% +/- 5.35%) in experiment A, and in
      experiment B the survival rate was 92.08% +/- 3.30% in the expansion group and
      80.79% +/- 4.52% in the delay group, showing significant difference (P < 0.01).
      CONCLUSION: Expansion prefabrication can and improve the survival of the crossing
      area supply axial pattern flap. The mechanism is the bridging effect.

PMID- 18630429
TI  - [Construction and identification of recombinant retroviral vector containing
      human interleukin 1 receptor antagonist and its expression in osteoarthritic
      human articular chondrocytes].
AB  - OBJECTIVE: To construct the retroviral vector containing human interleukin 1
      receptor antagonist (IL-1Ra) and to investigate the property of the transfected
      articular chondrocytes from osteoarthritic patients in vitro. METHODS: Retroviral
      vector PLXRN carrying IL-1Ra (PLXRN-IL-1Ra) gene was constructed by inserting IL
      1Ra gene at the sites of Sal I and BamH I. The recombinant retroviral plasmid was
      homologously recombinated in bacterial cells. After screening and amplification,
      the recombinant retroviral plasmid was obtained and transfected into PT67 cells.
      The replication-defective retrovirus PLXRN-IL-1Ra was packed and amplified in the
      PT67 cells. Viral titer was determined by infecting NIH/3T3 cells with serially
      diluted viral supernatants produced with a control vector. Experiments were
      divided into 3 groups: non-transduced group (group A), PLXRN transduction group
      (group B), PLXRN-IL-1Ra transduction group (group C). Primary articular
      chondrocytes from osteoarthritic patients were transduced with PLXRN and PLXRN-IL
      1Ra. The positive chondrocytes clones, which were G418-resistant, were cultured
      for 3-4 weeks after being selected by G418. The expression of IL-1Ra mRNA in the
      chondrocytes was determined by RT-PCR. Levels of IL-1Ra protein synthesis in the
      supernatants were measured by ELISA. RESULTS: Restrictive endonuclease
      identification and gene sequencing confirmed that the recombinant contained IL
      1Ra cDNA. Virus titer could reach 3 x 10(4) CFU/mL. Primary chondrocytes cultured
      in vitro were polygonal or spindle and were stained with purple particles by
      toluidine blue staining. After stable transduction into the chondrocytes the 311
      bp fragment of IL-1Ra was detected in group C by semi-quantitative RT-PCR. ELISA
      showed that IL-1Ra in supernatants of the group A and group B were below the
      level of detection. The concentrations were (60.47 +/- 15.13) ng/L in group C.
      There were significant differences between gene transduction group and control
      groups (P < 0.05). CONCLUSION: The construction of recombinant retrovirus vector
      by homologous recombination in bacterial cells can be quickly and easily
      performed. Stable and effective expression of IL-1Ra can be achieved by
      transduction with retroviral vectors in osteoarthritic articular chondrocytes,
      indicating potential utility in gene therapy for osteoarthritis.

PMID- 18630436
TI  - [A comparison of digital planimetry and transparency tracing based methods for
      measuring diabetic cutaneous ulcer surface area].
AB  - OBJECTIVE: To assess the reliability of diabetic cutaneous ulcer surface area
      (DCUSA) measurement using digital planimetry method (A) and transparency tracing
      method (B). METHODS: Images of diabetic cutaneous ulcers from 35 inpatients with
      diabetic skin ulcers from September 2005 to April 2007 were taken by a digital
      camera once a week or twice a week over a period of 12 weeks, resulting in 305
      photographs; the ulcers were traced on a grid with acetate wound tracings,
      simultaneously. A total of 305 pairs of DCUSA which were calculated respectively
      throughout digital camera combined with Image J medical imaging software and
      transparency tracing with grid sheet by two independent observers sequentially
      were obtained. The intraclass correlation coefficients (ICCs, one-way random
      effect model) was used as an indicator of chance-corrected agreement to estimate
      the relative reliability for the interobserver data. Multiple linear regression
      analysis was also used to measure the relationship of these two methods. RESULTS:
      DCUSA obtained from method A and obtained from method B was (4.84 +/- 7.73) cm2
      and (5.03 +/- 7.89) cm2, respectively; no significant difference was found (P >
      0.05). ICCs was high (ICCs = 0.949 for method B and 0.965 for method A),
      indicating that the relative reliability for the interobserver was excellent. The
      method A were highly correlated with measurements obtained from method B (r =
      0.957, P < 0.05). CONCLUSION: The digital planimetry method described in this
      study represents a simple, practical, without any wound damage and contamination,
      and inexpensive technique to accurately evaluate the areas of diabetic cutaneous
      ulcers. The photographic technique combined with Image J medical imaging software
      should be considered for wound measurement.

PMID- 18630431
TI  - [Development of chitosan/polyethylene glycols-succinate mitomycin C film drug
      delivery system and releasing character in vitro].
AB  - OBJECTIVE: To develop the chitosan/polyethylene glycols succinate (CH/PEG-SA)
      mitomycin C (MMC) film drug delivery system and its release effect in vitro.
      METHODS: MMC loading in composite films was determined using a UV-visible
      spectrophotometer. Freeze-dried films (90 mg) were immersed in 1 mL PBS buffer
      (pH 7.4). The concentrations of MMC releasing in vitro were calculated refer to
      the standard curve of relationship between the concentrations of MMC and the
      value of UV-visible spectrophotometer. The curve of the concentrations of MMC
      releasing from the films in vitro was drawn at different time. The relationship
      between the films, structure and the drug releasing was revealed. RESULTS: The
      films showed swelling without brittleness. The equation of Linear Regression was
      y=0.593x(3)-2.563x(2)+25.944x-0.236 (R2=1.000). The film had a good drug delivery
      capability. The samples weighing 20 mg were soaked into the liquid of PBS, the
      releasing concentrations of MMC were 14.9616 microg/mL at 12 days, 14.4824
      microg/mL at 18 days and 11.4092 microg/mL at 32 days, which was higher than ID50
      of MMC (10.4713 microg/L) to fibroblast. Then MMC was released at a low
      concentration. The releasing concentrations of MMC was 0.1793 microg/mL at 60
      days until being delivered completely. CONCLUSION: The flexibility is enhanced ,
      and the mechanical function is improved, so that there is better nature of
      membrane. The initial burst is avoided more effectively, and the drug releasing
      would be maintained for a certain time.

PMID- 18630432
TI  - [Effect of pulsed electromagnetic fields of different treatment time on bone
      mineral density of femur in ovariectomized rats].
AB  - OBJECTIVE: To observe the effect of pulsed electromagnetic fields (PEMFs) of
      different treatment time on bone mineral density of femur in ovariectomized rats,
      so as to find out the treatment time for the best therapeutic efficacy. METHODS:
      Fifty female SD rats were randomly divided into 5 groups: sham-ovariectomized
      (SHAM) group (no PEMFs treatment), ovariectomy (OVX) control group (no PEMFs
      treatment), OVX I, II and III groups (PEMFs treatment at 8 Hz frequency with 3.8
      x 10(-10) A/m intensity 20, 40, and 60 minutes daily for 30 days, respectively).
      All rats were given bilateral ovariectomy except those in the SHAM control group.
      Bone mineral density (BMD) of femur was assessed at 30 days after PEMFs
      treatment. RESULTS: In OVX control group, hypotrichosis, hypoactivity and
      listlessness were observed after operation; and in SHAM group, OVX I group, OVX
      II group and OVX III group, pilus, psyche and activity were normal. The BMD
      values were (0.226 +/- 0.011), (0.210 +/- 0.011), (0.231 +/- 0.013), (0.231 +/-
      0.017) and (0.229 +/- 0.013) g/cm2 in SHAM group, OVX control group, OVX I group,
      OVX II group and OVX III group respectively, showing significant differences
      between OVX control group and other groups (P < 0.05), but showing no significant
      differences between other 4 groups (P > 0.05). CONCLUSION: PEMFs of the three
      different treatment times can maintain the BMD in ovariectomized rats. It shows
      that PEMFs have the same effect of maintaining BMD with increasing of treatment
      time at the range of 20-60 minutes in ovariectomized rats.

PMID- 18630438
TI  - [Anatomy and clinical application of bypass circuit outflow tract of arterial
      sclerosis obstruction].
AB  - OBJECTIVE: To evaluate the possibility of collateral outflow tract of arterial
      sclerosis obstruction (ASO) and the prospect of clinical application. METHODS:
      The red emulsion was infused into the arteries of the above knee amputation of 10
      fresh specimens. Then the pathological changes of the anterior tibial artery,
      posterior tibial artery and the popliteal artery, and the contribution of these
      bole artery branch were observed. From September 2005 to April 2007, 5 patients
      with ASO were treated, unilateral lower limb was involved in all cases. There
      were 3 males and 2 females, aged 68-81 years. The arteriography and Color Doppler
      ultrasound of lower limbs showed that the femoral artery and the popliteal artery
      and the branches had no development. The exploratory operation on the popliteal
      artery and the branches was carried out. RESULTS: The walls of the anterior
      tibial artery, posterior tibial artery, and the popliteal artery were stiff and
      the lumens were filled with atheromatous plaque. The sural arteries opening to
      the bole artery was frequent. The collateral circulation at the knee perimeter
      was raritan rather affluent at the muscle group. All of the operations were
      successful, the skin temperature increased gradually after operation, and the
      degrees of blood oxygen saturation increased to 90%-100% at 6 hours from 0 before
      operation. After a follow-up of 3 to 12 months, the symptom improved obviously,
      rest pain disappeared, lower limb ulcer healed. The Color Doppler ultrasound
      showed that most of the blood flow at the anastomotic stoma ejected into bypass
      circuit, and the blood flow at the distally posterior tibial artery and anterior
      tibial artery was little. CONCLUSION: The collateral outflow tract construction
      is feasible, it is an effective path after clinical verification to solve the
      advanced stage ASO.

PMID- 18630435
TI  - [Feasibility study on repairing full-thickness abdominal wall defect with
      pedicled demucosal small intestinal sheet].
AB  - OBJECTIVE: To overcome the disadvantages of the artificial materials, to design
      pedicled demucosal small intestinal sheet to repair full-thickness abdominal wall
      defect. METHODS: The porcine model of full-thickness abdominal wall defect by
      resecting 10 cm x 7 cm abdominal wall tissue (from skin to peritoneum) in 20
      female animals, which were randomized to jejunum and ileum sheet groups(n = 10).
      Defect of abdominal wall were repaired with pedicled demucosal jejunum/ileum
      sheet respectively and immediate split-thickness free skin grafting. The general
      condition was observed and the tension strength of the repaired abdominal wall
      was measured 30 days postoperatively. In another 5 models, defect was repaired
      with pedicled demucosal small intestinal sheets and immediate split-thickness
      free skin grafting. The histological change and tissue thickness of the pedicled
      demucosal small intestinal sheet, split-thickness free skin graft and the
      repaired abdominal wall were observed and measured respectively after 30 days of
      operation. RESULTS: The operations were successful and no operative death
      occurred in all animals. All pedicled demucosal small intestinal sheets primarily
      healed to the edge of defected abdominal walls. Neither infection nor wound
      dehiscence occurred. All the split-thickness free skin grafting were successful.
      Regeneration of the intestinal mucosa occurred 4 days to 5 days postoperatively
      in 3 animals (2 of jejunum sheet group and 1 of ileum sheet group) at the initial
      stage and were successfully treated. No postoperative herniation occurred in all
      animals. The celiac pressure of herniation of the repaired abdominal wall
      jejunum/ileum sheet was (24.8 +/- 3.4) kPa in jejunum sheet group and (21.3 +/-
      2.8) kPa in ileum sheet group, and the difference was significant (P < 0.01). No
      rupture of the repaired abdominal wall occurred in jejunum and ileum sheet groups
      when the cel iac pressure was 40 kPa. Before repairing the abdominal wall
      defects, there was a little residual mucosal tissue on the surface of all
      pedicled demucosal small intestinal sheets. At the 30th day after operation,
      conspicuous hyperplasia and thickening occurred in all parts of tissue of the
      repaired abdominal walls and the residual mucosal tissue disappeared completely.
      CONCLUSION: Because of simple operation, satisfactory achievement ratio, good
      effect, no important complication, and no use of expensive prosthetic materials,
      it is a feasible method to repair the full-thickness abdominal wall defect with
      pedicled demucosal small intestinal sheet.

PMID- 18630437
TI  - [A comparative study on effect of bacterial load in diabetic foot ulcers dealing
      with iodophor and rivanol respectively].
AB  - OBJECTIVE: To investigate the change of bacterial load applied with iodophors and
      rivanol of diabetic foot ulcers (DFUs), furthermore to evaluate the effect of
      both in removing superficial microbes of DFUs. METHODS: From March 2006 to March
      2007, 30 patients were randomly divided into control group (group A, n = 10),
      iodophor group (group B, n = 10) and rivanol group (group C, n = 10). There were
      18 males and 12 females with an average age of 59.8 years (range 46-78 years).
      The wound size ranged from 3 cm x 2 cm to 15 cm x 10 cm. The disease course was 6
      weeks to 6 months (mean 2.1 months). Each wound was debrided and irrigated before
      process, then drug was compressed on the wound for 5 minutes, and irrigated
      again. The samples gained for three times, before, immediately and 24 hours after
      the process. Each sample was diluted before cultivation, the bacteria of wound
      were counted and compared among 3 groups. RESULTS: The cultures of specimens
      showed that the load decreased in every group, each cultured colony of specimen
      grew well, and there were no significant differences between 3 groups immediately
      after procedure (P > 0.05). There were significant differences between group B
      and groups A, C (P < 0.05), but there were no significant difference between
      group A and group C 24 hours after treatment (P > 0.05). CONCLUSION: Both
      iodophors and rivanol could remove the bacteria on the surface of wound. Topical
      germicide could reduced bacterial load in the wound of diabetic foot, the role of
      sterilizing and bacteriostasis of iodophors were better than that of rivanol.

PMID- 18630439
TI  - [Diagnosis and treatment of vascular injury in limbs].
AB  - OBJECTIVE: To report the diagnosis methods and clinical treatment effects of
      blood vessel trunk damage in limbs. METHODS: From January 2001 to June 2006, 72
      patients with vascular injury in limbs were treated. There were 50 males and 22
      females, aged from 5-60 years (median 39 years) and including 44 cases of open
      injury and 28 cases of closed injury. The locations were subclavian artery in 1,
      femoral artery in 23, popliteal artery in 20, radia artery and ulna artery in 12,
      brachial artery in 11, axillary artery in 3 and anterior and posterior tibia
      artery in 2. The disease course was 30 minutes to 27 days. Injured arteries were
      repaired by suturing directly in 3 cases, by end-end anastomosis in 39 cases and
      by saphenous transplantation in 30 cases. The length of transplant veins was 3 cm
      to 8 cm. RESULTS: In 72 cases, 67 survived and 5 were given amputation. Forty
      eight cases were followed up 6 months to 5 years. The blood flow rate and the
      diameter of blood vessel on the affected limbs were not different from that of
      normal limbs by colorful Doppler blood flow monitor. Forty cases recovered
      satisfactory limb function. Eight cases had different degrees of dysfunction, of
      them, four cases received functional reconstructive operation, and the function
      and appearance were improved. CONCLUSION: To investigate the mechanism and
      situation of injury, to examine patients carefully and analyze comprehensively
      are the key points of making earlier diagnosis for branch blood vessel damage;
      microsurgical repair of the injured blood vessel is the assurance of the blood
      flow rate. For the blood vessel above elbow and knee injured and lacked blood
      supply more than 4 hours and fascia syndrome, earlier opening the fascia cavity
      is the effective methods to recover the function of the limbs and to avoid
      disability.

PMID- 18630441
TI  - [Treatment of multiple arteries in renal transplantation from living related
      donors].
AB  - OBJECTIVE: To discuss renovascular reconstruction during living related donor
      kidney transplantation (LDKT). METHODS: Seventy-seven cases of LDKT from April
      2006 to March 2008 were retrospectively analyzed, including 63 cases in single
      renal artery group and 14 cases in multiple artery group. In multiple artery
      group, there were 3 cases of three arteries and 11 cases of double arteries; 9
      cases of donated left kidneys and 5 cases of donated right kidneys. Potential
      donors underwent fully medical evaluation before operation, including donor
      recipient human leucocyte antigen matching and a cross match test. The donor's
      operation of the incision either underneath the 12th rib approaching the dorsal
      lumbar was performed and the transplantation operation adopted the
      extraperitoneal approach in the contralateral fossa iliac. The arteries in the
      multiple artery group were implanted onto the external (or common) iliac artery
      different from the orthodox method. RESULTS: In multiple artery group, no blood
      transfusion during operation was performed, no complication occurred after
      operation and all donors were discharged after 7-9 days of postoperation. After a
      follow-up of 3 months to 1 year, all the recipients kept normal kidney function
      without renal tubule necrosis, renal artery embolism, vascular stenosis, urinary
      fistula and ureter necrosis. The ultrasound examination showed that the
      transplanted kidney had good blood supply. There was no significant difference in
      the time of urine secretion, serum creatinine level after 1 week of operation,
      length of hospitalization between the multiple artery group and the single artery
      group (P > 0.05). CONCLUSION: The accurate treatment of multiple artery
      anastomosis are critical for the safety of the LDKT.

PMID- 18630446
TI  - [Experimental study on losartan decreasing denervated skeletal muscle atrophy
      through reducing cell apoptosis].
AB  - OBJECTIVE: To explore the role of cell apoptosis in denervated skeletal muscle
      atrophy in rats and the effect of losartan on it. METHODS: Forty-two Sprague
      Dawley rats were randomly divided into 3 groups: group I (n = 14, normal control
      group), group II (n = 14, denervated group) and group III (n = 14, losartan
      group). The rats were not treated in group I, and were made denervated
      gastrocnemius models in groups II and III. In group III, the rats were treated
      with losartan 10 mg/kg x d by gavage and with normal saline in groups I and II.
      After 4 weeks, gastrocnemius mass to body mass ratio (GAS/BM) served as the
      degree of muscle atrophy. Apoptotic cells in gastrocnemius were stained in situ
      by using TUNEL. Gastrocnemius Bcl-2 and Bax protein were quantified by
      immunohistochemistry and Western blot. Bax/Bcl-2 served as the degree of
      apoptosis. RESULTS: The ratio of apoptosis was higher in group II than that in
      group I (11.32% +/- 4.51% vs 0.56% +/- 0.21%, P < 0.05). The ratio of apoptosis
      was lower in group III than that in group II (7.21% +/- 2.05% vs 11.32% +/-
      4.51%, P < 0.05). The atrophy of skeletal muscle (GAS/BM) in group II was more
      serious than that in group I (11.68 +/- 1.98 vs 12.86 +/- 0.74, P < 0.05), there
      was no significant difference between group III and group II (12.11 +/- 0.65 vs
      11.68 +/- 1.98, P > 0.05). The expression of Bcl-2 in group II (18.3% +/- 4.9%)
      was significantly lower than that in group I (27.5% +/- 2.8%) and group III
      (25.5% +/- 3.5%); there was no significant difference between group III and group
      I (P > 0.05). The expression of Bax in group II (24.1% +/- 3.1%) was
      significantly higher than that in group I (22.1% +/- 3.6%) and group III (21.7%
      +/- 2.3%); there was no significant difference between group III and group I (P >
      0.05). Western blot results showed that: the expressions of Bcl-2 were 122.5 +/-
      14.6 in group II, 135.3 +/- 6.2 in group I and 139.2 +/- 16.2 in group III;
      showing significant differences between group II and group I, between group III
      and group II (P < 0.05). The expressions of Bax were 107.1 +/- 15.8 in group II,
      89.3 +/- 8.4 in group I, and 94.2 +/- 9.5 in group III; showing significant
      differences between group II and group I, between group III and group II (P <
      0.05). There was no significant difference in the expression of Bcl-2 and Bax
      between group III and group I (P > 0.05). CONCLUSION: Cell apoptosis plays an
      important role in denervated skeletal muscle atrophy in rats and may be one of
      the factors causing skeletal muscle atrophy. Losartan can decrease skeletal
      muscle cell apoptosis through regulating the ratio of Bax/Bcl-2.

PMID- 18630448
TI  - [An economic and effective method for islet cell isolation from SD rats].
AB  - OBJECTIVE: To set up an economic and effective method for islet isolation from
      rat, and thereby prove a laboratory protocol of animal model for clinical islet
      transplantation. METHODS: Twenty-five adult male SD rats weighing 230-380 g were
      used as organ donor. In each of 5 repeated experiments, pancreatic islets of 5
      animals were isolated by intraductal infusion of compound sodium chloride
      injection (CSCI), and subsequently, digested with low concentration (0.5 mg/mL)
      of collagenase V solution. Islet purification was performed by using a
      discontinuous density gradient centrifugation that was prepared with 27.0%,
      23.0%, 20.5% and 11.0% of Ficoll 400. Islet yield and purity were determined by
      dithizon (DTZ) stain, and propidium iodide (PI)/fluorescein diacetate (FDA)
      double stain was used to check viability of islets. The endocrine secretory
      function was assessed by insulin secretion in either low (2.8 mmol/L) or high
      (25.0 mmol/L) glucose incubation after 3 days of culture in RPMI1640 media.
      RESULTS: Average islet digestion time of 5 experiments was (13.8 +/- 1.6) min.
      Before purification, average isolated number was (5,626 +/- 422) islets, and the
      number was significantly reduced to (2 914 +/- 485) islets after purification (P
      < 0.01). The average recovery rate was 51.6% +/- 6.0%, and the average yield was
      (583 +/- 97) islets/pancreas. The average purity and viability of islets were
      90.2% +/- 3.4% and 81.6% +/- 7.0%, respectively. After 3 days of culture, insulin
      secretion of the islets was (116.1 +/- 17.4) EU/L in high glucose incubation,
      which was significantly higher than that of low glucose environment [(39.7 +/-
      7.5) EU/L, P < 0.01)]. The average insulin stimulation index was 3.0 +/- 0.4.
      CONCLUSION: The islet isolation with the CSCI solution and digestion with low
      concentration of collagenase V decrease experimental cost and also have a
      beneficial effect on islet recovery and their function.

PMID- 18630445
TI  - [Micturition alert device dedicated to neurogenic bladders].
AB  - OBJECTIVE: To introduce a micturition alert device dedicated to neurogenic
      bladders. METHODS: The design and mechanism of the micturition alert device were
      explained, the effectiveness was tested in a cranin experiment. RESULTS: The
      micturition alert device consisted of a permanent magnet sutured on the anterior
      bladder wall and a warning unit sutured on the inferior abdominal wall. The
      warning unit was assembled with a compass-like switch, a power supply, a buzzer
      and a power switch. Bladder volume determined the position of the magnet which
      determined the magnetic field at the point of the warning unit. The change of
      magnetic field was read by the warning unit. With increasing bladder volume from
      initial state to 200 mL in 8 dogs, the magnet moved cranially 32.8 mm averagely
      (from 31.3 mm to 34.1 mm) and the hand of warning unit turned 52 degrees (from 47
      degrees to 57 degrees). The value of the warning unit was correlated positively
      to the bladder volume (r = 1.0, P < 0.01). If the desired bladder volume was
      determined as 150 mL to activate the warning unit to alarm in advance, the
      fullness of bladder was 147.6 mL averagely from 135 mL to 160 mL, with an error
      less than 15 mL (10%). CONCLUSION: The micturition alert device including a
      warning unit and permanent magnet could monitor bladder volume continuously and
      alarm in time for the patients with loss of micturition desire. It is simple,
      easily-made, cheap and conveniently used. It is worth of further study.

PMID- 18630440
TI  - [Clinical analysis of 55 cases of hemangioma in superficial body treated with
      copper needles].
AB  - OBJECTIVE: To analyze the clinical effect of retained copper needles well as
      neoplasm ligation, retained copper needles associated with Pingyangmycin
      injection and inserted copper needles followed by DC in treating hemangioma so as
      to treat hemangioma with copper needles. METHODS: From January 1999 to January
      2006, 55 cases of hemangioma in superficial body were treated with copper
      needles, including 28 males and 27 females and aging 3-50 years(median 19 years).
      There were 42 cases of cavernous hemangiomas, 4 cases of racemose hemangiomas and
      9 cases of multiplicative hemangiomas. The size ranged from 6 cm x 4 cm to 40 cm
      x 25 cm. Retaining copper needles were used in 29 cases, retaining copper needles
      with ligating neoplasm in 21 cases, retaining copper needles associated with
      Pingyangmycin injection in 3 cases and inserting copper needles followed by DC in
      2 cases. RESULTS: Fifty cases were treated with copper needles only once and 5
      cases twice. All cases were followed up for three to eighteen months. According
      to Wang Yongjie's criterion, 15 (27.3%) cases were cured, 38 (69.1%) improved,
      and 2 (3.6%) failed to respond; the response rate was 96.4% (53). CONCLUSION:
      Copper needle is effective for treating hemangioma in superficial body. Retaining
      copper needles with ligation neoplasm or with Pingyangmycin injection can achieve
      better effect.

PMID- 18630444
TI  - [Correction of inverted nipples by double stitching of U-shape].
AB  - OBJECTIVE: To introduce a way to correct mildly and moderately inverted nipple.
      METHODS: From May 2004 to January 2007, 16 patients (aged 18-38 years) with
      original bilateral inverted nipple were corrected with the double stitching of U
      shape. Sixteen cases included 11 mildly inverted nipples and 5 moderately
      inverted nipples. Six of them received massage and vacuum aspiration, and the
      results were not satisfactory. After the pulling out inverted nipples, four
      microincisions about 0.1 cm on the border of areola and the basilar part of
      nipple were designed in each horizontal and perpendicular directions, then double
      stitching was performed to increase the supporting and sustaining tissue under
      the nipple and close the way nipple invert. RESULTS: Most cases exhibited
      excellent aesthetic projection and incision healed by first intention. Followup
      examinations were performed at 6 months to 2 years and revealed no evidence of
      recurring inversion, nipple tilting or lactation disturbance. No surgical
      complications such as infection, nipple and areola of breast necrosis, permanent
      numbness. The scars in the local site were limited and not conspicuous.
      CONCLUSION: Double stitching of U-shape is easy and simple with few
      complications. It is an ideal method to correct mild and moderate inverted
      nipple.

PMID- 18630442
TI  - [Roles of placental growth factor in percutaneous coronary angioplasty and stent
      implantation].
AB  - OBJECTIVE: To investigate the value of plasma placental growth factor (PlGF) in
      percutaneous coronary angioplasty and stent implantation. METHODS: From May 2006
      to March 2007, 61 patients (53 males and 8 females, mean age 61 years) and 28
      normal controls were included. All patients present with acute chest pain and
      underwent coronary angiography, the lesion severity of coronary arteries was
      assessed by Gensini coronary scoring system. Of them, 26 patients having serious
      coronary lesion underwent (percutaneous transluminal coronary angioplasty, PTCA)
      and stent implantation. Cardiovascular events were recorded after 30 days. Plasma
      PlGF was determined by ELISA. RESULTS: According to the angiography, the patients
      could be divided into CAD group (n = 45) and Non-CAD group (n = 16). Plasma PlGF
      level in CAD group was significantly higher than that in Non-CAD group and
      control group [(10.70 +/- 0.49) ng/L vs (4.53 +/- 0.64) ng/L vs (3.64 +/- 0.36)
      ng/L, P < 0.001)], and there was no significant difference between the non-CAD
      group and control group (P > 0.05). A significant positive correlation was found
      between Gensini coronary score and plasma PlGF level (r = 0.918, P < 0.01).
      Moreover, patients with cardiovascular events had a higher PlGF level than those
      without cardiovascular events after PTCA and stent implantation [(13.98 +/- 3.39)
      ng/L vs (7.25 +/- 2.96) ng/L, P < 0.01)]. CONCLUSION: PlGF level has diagnostic
      value in patients with acute chest pain. The measurement of plasma PlGF might be
      helpful for early diagnosis of coronary artery disease. Patients with higher
      plasma PlGF level may have more severe coronary lesion. PlGF may be one of
      predictors for cardiovascular events after PCI.

PMID- 18630443
TI  - [Early outcome of one-stage transnasal surgery combined with transnasal surgery
      for cranionasal tumors and reconstruction of skull base].
AB  - OBJECTIVE: To investigate the microsurgical management of cranionasal tumors and
      the method of the reconstruction of the skull base. METHODS: From June 2005 to
      October 2007, 20 patients with cranionasal tumor were treated. There were 10
      males and 10 females, aged between 13 and 77 years (median 49 years). The disease
      course was 2 months to 13 years. The cranionasal tumors, proved by MRI and CT
      scans, located in the anterior skull base, paranasal sinus, nasal and/or orbit
      cavity. And their clinical presentations were listed as follows: dysosphresia in
      14 patients, headache in 11 patients, nasal obstruction in 9 patients, epistaxis
      in 8 patients, visual disorder in 4 patients, exophthalmos in 4 patients and
      conscious disturbance in 2 patients. All 20 patients underwent transnasal surgery
      combined with transnasal surgery, and tumors were resected by one-stage
      operation. The skull base was reconstructed by surgical technique "Pull Down
      Sandwich" with pedicle periosteum flap. RESULTS: Tumors were resected by one
      stage operation, and the anterior skull bases were reconstructed. Pathological
      examination showed 8 cases of malignant tumors and 12 cases of benign tumors. The
      total surgical excision was complete in 16 patients, and 4 patients with subtotal
      excision. There was no operative death. Eighteen patients were followed up 3
      months to 2 years and 6 months. Transient cerebrospinal fluid rhinorrhea was
      found in 2 cases which were cured by lumbar drainage. And recurrence of tumor was
      observed in 5 patients 3 months to 2 years after operation. CONCLUSION:
      Microsurgical operation via subfrontal approach assisted by transnasal endoscopy
      is an effective method in management of cranionasal tumors, with the advantages
      of reconstruction of the skull base with pedicle periosteum flap or "Pull Down
      Sandwich" and low complication rate.

PMID- 18630451
TI  - Fibromatosis of the head and neck: morphological, immunohistochemical and
      clinical features.
AB  - The term fibromatosis indicates a proliferation of well-differentiated
      fibroblasts and myofibroblasts that develops in the soft tissue. This tumor has
      been considered locally aggressive because of the infiltrative growth pattern,
      but does not metastasize. Its occurrence in the head and neck region is not
      common, and very sporadically it may occur in the oral cavity or jaw bones. Two
      cases of adult fibromatosis are described here; one involving the submucosa of
      the middle hard palate and the other the subcutaneous area of the frontal bone.
      Tumor growth was rapid and bone involvement occurred in one case. Biopsies were
      taken and in both cases histological examination showed a tumor consisting of
      fibroblasts within a collagenous stroma, with rare atypia and mitoses. The
      patients underwent surgical resection with wide surgical margins; excised
      material was analyzed microscopically and a diagnosis of fibromatosis was
      rendered. Immunohistochemistry was positive for actin, vimentin and desmin, and
      negative for S-100, CD34, the progesterone receptors (PR)-A and PR-B and the
      estrogen receptors (ER)alpha and ERbeta. Follow-up at 5 years after surgery found
      both patients to be progression free. The clinical, histological and
      immunohistochemical features were analyzed to better characterize this form of
      the disease, that very rarely involves the oral cavity.

PMID- 18630447
TI  - [Clinical application of bio-derived bone transplantation with tissue engineering
      technique: 7 year follow-up].
AB  - OBJECTIVE: To summarize the medium-term clinical result of bio-derived bone
      transplantation in orthopedics with tissue engineering technique. METHODS: From
      December 2000 to June 2001, 10 cases of various types of bone defect were treated
      with tissue engineered bone, which was constructed in vitro by allogenous
      osteoblasts from periosteum (1 x 10(6)/mL) with bio-derived bone scaffold
      following 3 to 7 days co-culture. Six men and 4 women were involved in this
      study, aged from 14 to 70 years with a median of 42 years. Among them, there were
      2 cases of bone cyst, 1 case of non-union of old fracture, 6 cases of fresh
      comminuted fracture with bone defect, and 1 case of chronic suppurative
      osteomyelitis. The total weight of tissue engineered bone was 3-15 g in all the
      cases, averaged 7.3 g in each case. RESULTS: The wound in all the case healed by
      first intention. For 7 year follow up, bone union was completed within 3.0 to 4.5
      months in 9 cases, but loosening occurred and the graft was taken out 1 year
      after operation in 1 case. The X-ray films showed that 9 cases achieved union
      except one who received resection of the head of humerus. No obvious
      abnormalities were observed, and the function of affected limbs met daily life
      and work. CONCLUSION: Bio-derived tissue engineered bone has good osteogenesis.
      No obvious rejection and other complications are observed in the clinical
      application.

PMID- 18630450
TI  - [A comparative study on immunocompatibility and histological turnover after fresh
      or preserved human amniotic membrane xenotransplantation].
AB  - OBJECTIVE: To investigate the immunoreaction, histological reaction and turnover
      by comparing the xenotransplantation of fresh human amniotic membrane (HAM) with
      that of preserved HAM, and to analyze the clinical application value of different
      kinds of HAM preparations. METHODS: Subcutaneous implant models were established
      in 150 BALB/C mice, which were randomized into 5 groups of 30 mice each, based on
      different implants: fresh amniotic membrane (FAM), double fresh amniotic membrane
      (DFAM), glycerin preserved amniotic membrane (GPAM), chorion (positive control)
      or merely operation (negative control). The tissue samples from grafted area were
      observed with SABC and HE staining, and the inflammatory cells were calculated
      with light microscopy. 1, 2, 4, 8 and 12 weeks after surgery. RESULTS: The mice
      in all of groups were normal in eating and moving, and the wound surface healed
      well. In all of AM groups, the expression of MHC II and the calculation of
      inflammatory cells were much less than those in chorion groups, showing
      significant differences (P < 0.01). At 1, 8 and 12 weeks after surgery, there
      were no significant differences in the expression of MHC II and the calculation
      of inflammatory cells in all of AM groups, compared with other groups (P > 0.05).
      From 2 weeks to 4 weeks after surgery, there were no significant differences in
      the expression of MHC II and the calculation of inflammatory cells between FAM
      and DFAM groups (P > 0.05), but they were both more than those in GPAM groups,
      showing significant differences (P < 0.05). At the 4th week after surgery, in all
      of AM groups, the expression of MHC II and the calculation of inflammatory cells
      were less than those at the 2nd week, showing significant difference (P < 0.01).
      The amniotic epithelium was still alive in fresh AM groups until 4 weeks after
      transplantation. Early after surgery, fibroblasts infiltrated AM from the
      substantia basilaris layer while made fibrous capsule around the epithelium.
      After 12 weeks, the amnion absorbed. CONCLUSION: As a kind of heterologous
      biomaterial, whether fresh or preserved, HAM can be seemed of ideal
      immunocompatibility and histocompatibility. Fresh HAM with alive epithelium may
      be more successful in area of repair and reconstruction.

PMID- 18630452
TI  - Feasibility assessment of a chemoresponse assay to predict pathologic response in
      neoadjuvant chemotherapy for breast cancer patients.
AB  - BACKGROUND: For chemosensitivity and resistance assays to be clinically useful in
      predicting patient outcome, they should require small amounts of tissue and be
      highly reproducible and reliable. PATIENTS AND METHODS: Expanded tumor cells from
      transcutaneous biopsies of breast lesions (n=62) were tested for chemoresponse
      using the cell-based ChemoFx assay. Pathologic complete response (pCR) was
      determined on a subset of patients (n=34). Assay score and pCR were determined
      independently in a blinded manner. Logistic regression models were used to select
      predictors for response. RESULTS: Tumor cells were successfully isolated from
      83.9% of patients. Chemoresponse profiles were robust and reproducible with
      coefficient of variance of <3%. In a limited initial patient outcome correlation,
      assay score of docetaxel/capecitabine significantly predicted pCR; the cross
      validated model was 75% accurate. CONCLUSION: It is feasible to assess the
      chemoresponsiveness of small breast lesions using the ChemoFx assay to assist in
      choosing neoadjuvant chemotherapy for breast cancer patients.

PMID- 18630449
TI  - [Effect of hepatocyte growth factor on proliferation of cultured human eccrine
      sweat gland epithelial cells].
AB  - OBJECTIVE: To investigate the effect of hepatocyte growth factor (HGF) on
      proliferation of cultured human eccrine sweat gland epithelial cells (hESGc) and
      the involvement of phosphorylation of ERK1/2. METHODS: hESGc were cultured in
      keratinocyte serum free medium (KSFM) and the first generation of hESGc was
      harvested. The expression of C-met was detected by immunocytochemistry. MTT assay
      was used to detect the effect of HGF on the proliferation of hESGc. The cells
      were divided into blank group, control group and experimental group. The culture
      density was 2 x 10(3) cells/hole in control group and experimental group. Two
      hundred microL KSFM with HGF in different levels was added to every hole. hESGc
      were cultured in KSFM with HGF at different levels (2, 20, 40 and 80 ng/mL) in
      experimental group, in KSFM without HGF in control group, and in KSFM without HGF
      and no hESGc in blank group. The cell proliferation was observed in experimental
      group 2 and 4 days later. Western blot was used to detect the expression of
      phosphorylated ERK1/2 at 40 ng/mL HGF after 0, 5, 30, 90 and 120 minutes.
      RESULTS: The results were positive for anti-C-met staining in the cytoplasm. HGF
      (40 ng/mL and 80 ng/mL) significantly improved the proliferation of hESGc (P <
      0.05). When cultured in the KSFM with 40 ng/mL HGF, the cell proliferation rate
      and the absorbance were 74.2%, 0.2393 +/- 0.0709 at 2 days and 74.8%, 0.2878 +/-
      0.0743 at 4 days; showing significant differences when compared with control
      group (P < 0.05). When cultured in KSFM with 80 ng/mL HGF, the cell proliferation
      rate and the absorbance were 54.5%, 0.2123 +/- 0.0592 at 2 days and 40.3%, 0.2310
      +/- 0.0567 at 4 days; showing significant differences when compared with control
      group (P < 0.05). The expression of p-ERK1/2 reached to the maximum after
      stimulation of 40 ng/mL HGF for 5 minutes, and relative integral absorbance (RIA)
      was 0.5932 +/- 0.1922, increased 8.1 times compared with instant stimulation (P <
      0.01). CONCLUSION: HGF could induce the proliferation of hESGc and activate the
      phosphorylation of ERK 1/2 protein.

PMID- 18630453
TI  - Expression of thymidylate synthase in liver and lung metastases of colorectal
      cancer and their matched primary tumours.
AB  - BACKGROUND: In advanced colorectal cancer (CRC) a low expression of thymidylate
      synthase (TS) in metastases predicts a higher response to 5-fluorouracil (5-FU).
      The purpose of this study was to investigate the expression of TS in liver and
      lung metastases of CRC and their matched primary tumours. PATIENTS AND METHODS:
      Immunohistochemical analysis of TS expression was performed on tissue samples of
      48 CRC metastases (liver n=38, lung n=10) and their matched primary tumours
      (n=45). RESULTS: There was no significant correlation between TS expression in
      33/48 (69%), matched samples of metastases and primary tumours (r=0.02, p=1.0).
      CONCLUSION: This study indicates that TS expression in liver and lung metastases
      of CRC does not always reflect the level of TS in their corresponding primary
      tumours. Therefore, it might not be accurate to solely rely on analyses of TS in
      the primary tumours to predict the effect of 5-FU-based chemotherapy in
      metastatic CRC.

PMID- 18630455
TI  - Matrix metalloproteinase-9 (MMP-9) immunoreactive protein in urinary bladder
      cancer: a marker of favorable prognosis.
AB  - BACKGROUND: [corrected] The purpose of this study was to explore whether changes
      in matrix metalloproteinase-9 (MMP-9) are involved in the progression of urinary
      bladder cancer and whether they have any prognostic value. PATIENTS AND METHODS:
      Overexpression of MMP-9 was evaluated in the primary tumor of 87 urinary bladder
      cancer cases with immunohistochemical staining. RESULTS: Of the urinary bladder
      carcinomas, 38% showed an overexpression (>25%) of MMP-9 immunoreactive protein.
      Increased positivity for MMP-9 correlated with favorable overall survival of the
      urinary bladder cancer patients. The 5-year overall survival and relapse-free
      survival was 68% and 36% in patients showing high MMP-9 expression and 48% and
      19% in patients with low (<25%) or negative MMP-9 expression (p=0.006, p=0.08,
      respectively). In multivariate analysis, MMP-9 overexpression seems to retain its
      independent prognostic value. CONCLUSION: This study shows that MMP-9 expression
      in urinary bladder carcinoma is associated with better prognosis.

PMID- 18630456
TI  - Natural history of established low grade cervical intraepithelial (CIN 1)
      lesions.
AB  - THE AIM of the present study was to ascertain the natural history of cervical
      intraepithelial lesions 1 (CIN 1) and to develop recommendations to optimize
      follow-up. PATIENTS AND METHODS: Patients referred for colposcopy from January,
      1996 to July, 2005 were reviewed. A prospectively maintained database was
      quarried for demographic, clinical, and pathologic data. RESULTS: The cohort
      included 1,001 patients with CIN 1. At 6 months, 330 patients (49%) regressed to
      normal, 305 (45%) had persistent low grade, while 45 (7%) progressed to high
      grade lesions. At 12 months, of those with negative pathology at 6 months, 200
      (80%) remained negative, 42 (16%) demonstrated low grade and 9 (4%) progressed to
      high grade lesions. Of those with low grade lesions at 6 months, 131 (50%)
      regressed, 121 (46%) had persistent low grade, and 10 (4%) progressed to high
      grade lesions. CONCLUSION: Our data demonstrates a low rate of progression for
      CIN 1, suggesting it may be reasonable to prolong the screening interval in women
      with CIN 1.

PMID- 18630458
TI  - The depth of tumor invasion beyond the outer border of the muscularis propria as
      a prognostic factor for T3 rectal/rectosigmoid cancer.
AB  - The distance of tumor invasion beyond the outer border of the muscularis propria
      (DBM) was measured whether it would be useful as a prognostic factor of the
      locally advanced rectal and rectosigmoid cancer was analyzed. PATIENTS AND
      METHODS: One hundred patients with rectal and rectosigmoid cancer invaded beyond
      muscularis propria who underwent surgery between 1996 and 2000 were included in
      this study. Patients who died due to other disease were excluded. Univariate and
      multivariate analyses of the risk factors including DBM for disease-free and
      cancer-related survival after surgery were performed. RESULTS: The median DBM was
      4,000 microm and patients were thus classified into 2 groups by DBM (<4,000
      microm and > or =4,000 microm). In univariate analysis, patients with a DBM of >
      or =4000 microm had a significantly poorer prognosis both for cancer-related
      survival (CRS) (p=0.004) and disease-free survival (DFS) (p=0.0025). Within many
      prognostic factors, lymphatic invasion (p=0.025), venous invasion (p=0.0402) and
      pattern of tumor infiltration (p=0.043) significantly correlated with DBM. In
      multivariate analysis with other factors including histology (p=0.0403), node
      status (p=0.0003), lymphatic invasion (p=0.0004), venous invasion (p<0.0001),
      tumor budding (p=0.0343) and pattern of tumor infiltration (p=0.0160), DBM was
      selected as the most significant prognostic factor for both CRS (hazard ratio
      (HR): 2.1682, 95% confidence interval (CI): 1.3606-3.8097, p=0.0019) and DFS (HR:
      2.0654, 95% CI: 1.2696-3.8257, p=0.0075). CONCLUSION: Since DBM was the most
      significant prognostic factor, it could be used to categorize T-factor in
      clinical staging of advanced rectal and rectosigmoid cancer.

PMID- 18630454
TI  - Impact of fresh frozen plasma on hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND: Little is known about the effect of transfusing fresh frozen plasma
      on the outcome after hepatectomy for hepatocellular carcinoma. PATIENTS AND
      METHODS: Among 410 patients who underwent curative resection between 1992 and
      2005, 180 patients had perioperative transfusion with whole blood or packed red
      blood cells and fresh frozen plasma (group A), while 46 patients were only
      transfused with packed red cells (group B), 43 patients were only transfused with
      fresh frozen plasma (group C) and 141 patients had no transfusion (group D).
      RESULTS: Group C had significantly fewer postoperative complications and a
      shorter hospital stay than group A. Preoperative coagulation was significantly
      worse in group C. Survival was significantly better in groups C and D than in
      group A. CONCLUSION: Perioperative transfusion of fresh frozen plasma improves
      clotting factors without an adverse influence on the survival of patients with
      liver dysfunction undergoing resection of hepatocellular carcinoma.

PMID- 18630457
TI  - Darbepoetin alfa administered every three weeks (Q3W) in anemic cancer patients
      receiving chemotherapy (CT).
AB  - BACKGROUND: Darbepoetin alfa, has a longer halflife than epoetin alfa (rHuEPO)
      due to its increased sialylated carbohydrate content and can be administered less
      frequently. Its advantage in terms of response is not entirely clear. PATIENTS
      AND METHODS: From August 2005 until October 2006, 64 anemic patients (hemoglobin
      < or =11.5 g/dl) with advanced metastatic cancer receiving chemotherapy (CT),
      median age 65 years (range 33-77), median Eastern Cooperative Oncology Group
      (ECOG) performance status (PS) 1 (range 0-1), were treated with subcutaneous
      (s.c.) darbepoetin alfa 500 microg every 3 weeks (Q3W) and a single intravenous
      (i.v.) dose of 125 mg of elemental iron at the beginning of the treatment period
      followed by an oral daily iron supplement (200 mg of elementary iron). The
      treatment effect was evaluated as a response (Hb increase > or =1 g/dl) or a
      major response (Hb increase > or =2 g/dl) after 2, 4, 6 and 8 weeks. The patients
      were questioned about fatigue. RESULTS: After 8 weeks of treatment, a treatment
      response was observed in 11 out of the 29 evaluable patients (38%) with a major
      response in 10%. The mean Hb change was 0 g/dl, +0.9 g/dl, +0.75 g/dl and +0.7
      g/dl respectively at 2, 4, 6 and 8 weeks. Blood transfusions were required in 9
      patients (31%). At baseline, 39 out of the 64 patients (61%) reported grade 1 or
      2 fatigue. At 8 weeks the patients with a major response did not show any
      evidence of fatigue. CONCLUSION: Darbepoetin alfa Q3W is moderately effective in
      reducing anemia in heavily pretreated and advanced stage chemotherapy treated
      patients.

PMID- 18630461
TI  - Polymorphism in MHC class II transactivator gene is not associated with
      susceptibility to colorectal cancer in Swedish patients.
AB  - BACKGROUND: Reduced expression of major histocompatibility complex class II (MHC
      II) genes in colorectal cancer (CRC) has been reported. MHC-II transactivator
      (CIITA), encoded by the MHC2TA gene, is considered to be the master regulator for
      MHC-II gene expression. A functional single nucleotide polymorphism (SNP) -168A-
      >G in the promoter region of the MHC2TA gene is suggested to have an influence on
      different autoimmune diseases. PATIENTS AND METHODS: Our study was performed to
      evaluate the association between the -168A-->G MHC2TA gene variant in patients
      with CRC versus a control group. Using the TaqMan system, this SNP was screened
      in 248 CRC patients and 256 controls. RESULTS: No significant difference in
      genotype distribution or in allelic frequencies was found between the two groups,
      nor any association with clinical characteristics. CONCLUSION: The results of
      this study suggest that -168A-->G polymorphism of the MHC2TA gene is not
      associated with susceptibility to CRC.

PMID- 18630468
TI  - Complete response obtained and maintained by combination of S-1 and CPT-11 in
      hepatic metastases of colon cancer: a case report.
AB  - BACKGROUND: An oral combined fluoropyrimidine, S-1 (tegafur, gimeracil and
      oteracil) has recently been used alone or in combination for colorectal cancer
      (CRC). CASE AND METHODS: A 67-year-old man underwent left hemicolectomy for the
      descending colon cancer with multiple hepatic metastases. A combined chemotherapy
      with S-1 and irinotecan (CPT-11) was started after surgery. After three courses
      of the chemotherapy, no metastasis was observed in contrast computed tomography
      with decline of tumor markers. The patient was judged to have achieved a complete
      response (CR). The chemotherapy, continued on an outpatient basis, has maintained
      the CR for 15 months so far, though adverse reactions such as neutropenia,
      thrombocytopenia, and hypolacrimia have occurred. CONCLUSION: This case indicates
      that the combination of S-1 and CPT-11 is feasible on an outpatient basis and has
      potential as one of the treatment choices for hepatic metastasis from CRC.

PMID- 18630460
TI  - Postoperative adjuvant chemotherapy in surgically staged grade 3 endometrial
      cancer.
AB  - BACKGROUND: The effectiveness of postoperative adjuvant chemotherapy for
      surgically staged grade 3 endometrial cancer was investigated. PATIENTS AND
      METHODS: Sixty-three consecutive patients with grade 3 endometrial cancer (49
      with surgical stage I-II disease and 14 with stage III disease) were treated
      surgically. Postoperatively, 40 patients (63.5%) were treated with a chemotherapy
      regimen consisting of ifosfamide, epiadriamycin, and cisplatin scheduled for 3-5
      cycles. No patient underwent radiotherapy. RESULTS: Recurrence developed in 8 out
      of the 63 patients, all within two years. Six of the 8 recurrences were found to
      be extrapelvic lesions. Recurrences occurred predominantly at distant sites in
      the absence of pelvic radiation. Estimated 5-year disease-free survival rates
      were 89.8% for patients with surgical stage I-II disease, 78.6% for those with
      surgical stage III disease, and 87.3% overall. CONCLUSION: The current study
      suggests the potential role of adjuvant chemotherapy alone in grade 3 endometrial
      cancer.

PMID- 18630462
TI  - Differences in expression of tumor markers between pre- and postmenopausal women
      with invasive cervical cancer.
AB  - THE AIM of the present study was to investigate the differences in the expression
      of tumor markers in squamous cell and in adenomatous carcinomas in pre- and
      postmenopausal women, respectively. PATIENTS AND METHODS: The study population
      comprised 53 premenopausal and 107 postmenopausal women. Thirty-four tumors were
      adenomatous (n=31) or adenosquamous carcinomas (n=3), distributed between 13
      premenopausal and 21 postmenopausal women. The remaining 126 squamous cell
      carcinomas were diagnosed in 40 pre- and 86 postmenopausal women. Expression of
      ten tumor markers of possible clinical importance in cervical cancer was
      evaluated. RESULTS: Expression of three tumor markers, p53 (>0% vs. 0%), p27 (>
      or =20% vs. <20%) and cyclooxygenase-2 (COX-2) (high intensity vs. moderate/none)
      differed significantly between pre- compared to postmenopausal women with
      squamous cell (p27; 54% vs. 72%, p=0.009) or adenomatous carcinomas (p53; 8% vs.
      63%, p=0.006 and COX-2; 46% vs. 20%, p=0.03). All results were adjusted for
      clinical cancer stage. CONCLUSION: The unusual age-specific incidence curve in
      cervical cancer has rarely been related to expression of tumor markers. Age
      related differences in expression of tumor markers could reflect some age-related
      different biological mechanisms in cervical cancer.

PMID- 18630463
TI  - Changes in tumour biological markers during primary systemic chemotherapy (PST).
AB  - BACKGROUND: The influence of primary systemic therapy (PST) on the expression of
      relevant therapeutic markers is still under investigation. PATIENTS AND METHODS:
      Corresponding "baseline" biopsies and post-chemotherapy surgical specimens from
      87 patients treated with neoadjuvant anthracycline- or taxane-based chemotherapy
      were analysed for the expression of the oestrogen receptor (ER), the progesterone
      receptor (PR), the B-cell lymphoma protein 2 (Bcl-2), the v-erb-b2 erythroblastic
      leukemia viral oncogene homolog 2 (Her2/neu), the tumour protein p53 and the
      proliferation-related Ki-67 antigen. RESULTS: The pathological response rate was
      70%. Twenty-three tumours (26%) changed hormone receptor classification after
      chemotherapy (7, ER; 16 PR). A significant change was also observed for Her2/neu
      status. Eleven tumours which were positive prior to PST down-regulated Her2/neu
      after chemotherapy. The median Ki-67 index decreased from 30% before to 13% after
      treatment (p<0.01). Minor changes were observed in the expression of Bcl-2 and
      p53 (9%). Only the reduction of Ki-67 was associated with pathological response
      to PST. CONCLUSION: Her2/neu status as well as ER and PR status should be re
      evaluated on post-chemotherapy surgical specimens since changes can be observed.

PMID- 18630464
TI  - Rectal cancer adjuvant chemotherapy: when is more useful?
AB  - THE AIM of the study was to evaluate time-to-progression (TTP) of rectal cancer
      in a group of patients receiving adjuvant chemotherapy (CHT) after combined
      neoadjuvant treatment. A secondary end-point was to identify the possible
      influence of clinical TNM (cTNM) or pathological TNM (pTNM) on TTP and overall
      survival (OS). PATIENTS AND METHODS: From January 2000 to December 2005, 101
      consecutive rectal cancer patients who had been neoadjuvantly treated and had
      underne adjuvant CHT were retrospectively examined. The variables considered were
      age, gender and clinical and pathological effect of CHT administration. RESULTS:
      The mean age was 59 years (29-78 years) and the male:female ratio, 61:40. Forty
      two patients had a lower (< or =5 cm from the anal verge), 54 a middle (from 6 to
      10 cm) and 5 a higher (=10 cm) rectal lesion. All the patients had received the
      full course of neoadjuvant radiotherapy (RT) while 26.7% patients had received a
      reduced number of neoadjuvant CHT cycles. All the patients had undergone surgery
      and had received adjuvant chemotherapy which was completed in only 77.2% of the
      cases. Tumour down-staging and complete remissions were reported in 75.2% and
      14.8% of cases, respectively. TTP and OS at 3 years were 81.2% and 91.1%,
      respectively. Out of locally recurrent patients, 77.8% were N+ (p=0.0026) at the
      pathological evaluation. CONCLUSION: In our series, neither administration of
      oxaliplatin-based adjuvant chemotherapy (p=0.44) nor age > or =70 years (p=0.51),
      clinical stage III (p=0.67), tumour down-staging (p=0.44) and achievement of pCR
      (p=0.66) appeared to have a significant impact on TTP; only pN+ (patients "not
      responders" to a neoadjuvant CHT-RT) influenced local relapse requiring more
      accurate postoperative treatment and confirming the literature data about the
      utility of adjuvant therapy in stage III disease.

PMID- 18630465
TI  - Palliative treatment for elderly patients with colon cancer in ten Italian
      medical oncology units.
AB  - BACKGROUND: Palliative chemotherapy significantly reduces mortality in patients
      with stage IV colon cancer, but is less prescribed with rising age. In this
      paper, we highlight the pattern of palliative treatment and possible effects on
      survival among elderly patients. PATIENTS AND METHODS: From January to December
      2004, 78 files on the management of stage IV colorectal cancer (CRC) patients
      over 70 years, collected from 10 Italian Centres, were retrospectively examined.
      Determinants of receipt of palliative chemotherapy and their relation to toxicity
      and survival were considered. RESULTS: The proportion of elderly patients
      receiving first-line palliative chemotherapy was 98.7% and it was evaluated
      according to age, gender, educational level and comorbidities; patients receiving
      second-line therapy comprised 47.4%, those receiving third-line therapy 14.1% and
      those treated with a fourth-line therapy totalled 2.6%. Forty-one percent of
      patients received best supportive care (BSC) alone. CONCLUSION: In Italy, a
      proportion of elderly patients with metastatic chemonaive CRC are usually treated
      with a tolerability and overall survival similar to those for the younger
      population. Among progressive patients after second-line therapy, 45.8% usually
      undergo third line therapy; the remaining 54.2% undergo BSC.

PMID- 18630459
TI  - Retrospective study of S-1 versus tegafur/uracil and oral leucovorin in patients
      with metastatic colorectal cancer.
AB  - THE AIM of this study was to compare the efficacy and toxicity of S-1 to an oral
      combination regimen of tegafur and uracil (UFT) with leucovorin (LV) in
      metastatic colorectal carcinoma (CRC) patients. PATIENTS AND METHODS: Fifty-two
      patients were treated with either S-1 (80 mg/m2/d), administered for 28 days
      every 42 days, or UFT (300 mg/m2/d) and LV (90 mg/d), administered for 28 days
      every 35 days. The clinical results were compared retrospectively. RESULTS: There
      were no statistically significant differences in overall response between the two
      patient groups. The overall response rate was 11.8% in the S-1 group, and 11.1%
      in the UFT/LV group. No statistically significant difference in-time- to
      progression (TTP) or survival time was observed between the treatments. The
      median survival time was 29 months with S-1 and 12 months with UFT/LV.
      CONCLUSION: The oral S-1 provided similar safety and efficacy, compared to UFT/LV
      for metastatic CRC.

PMID- 18630467
TI  - Prognostic value of immunohistochemical analysis of tumor budding in colorectal
      carcinoma.
AB  - BACKGROUND: Tumor 'budding' of colorectal carcinoma along the invasive margin has
      been associated with increased malignant potential. This study investigated the
      possible prognostic significance of budding in invasive colorectal carcinoma.
      PATIENTS AND METHODS: Specimens resected from 149 patients who underwent
      potentially curative surgery for invasive colorectal carcinoma were studied.
      Budding was defined according to Ueno's criteria; budding intensity was assessed
      by examination of hematoxylin-eosin (HE)-stained specimens and
      immunohistochemical (IHC)-stained specimens using anti-cytokeratin antibody and
      anti-lymphatic vessel antibody. RESULTS: Immunohistochemical analysis identified
      many more budding foci that were not detectable by examination of HE-stained
      specimens. Multivariate analyses revealed that budding identified using
      immunohistochemical staining was a significant prognostic marker for disease-free
      survival and there was significant correlation between budding and microlymphatic
      vessel infiltration at the invasive tumor front. CONCLUSION: Budding,
      particularly as assessed with immunohistochemical staining, is a useful predictor
      of poor prognosis in patients with invasive colorectal carcinoma.

PMID- 18630466
TI  - Nuclear beta-catenin expression at the invasive front and in the vessels predicts
      liver metastasis in colorectal carcinoma.
AB  - Beta-catenin is a component of the Wingless/Wnt signaling pathway and can
      activate target genes associated with proliferation and invasion, linking with
      the APC gene. The purpose of this study was to investigate whether nuclear
      expression of beta-catenin in cells at the invasive front or in the vessels was
      associated with liver metastasis in human colon cancer. PATIENTS AND METHODS: One
      hundred and eighteen patients with colorectal carcinoma who underwent surgical
      resection (45 patients with liver metastasis and 73 patients without liver
      metastasis at least 5 years after surgery) were included in the study.
      Proliferative activity was determined in several areas (tumor center, invasive
      front and in the vessels) by immunohistochemistry and whether it was correlated
      with liver metastasis was examined. RESULTS: In 73.1% of primary tumors, positive
      staining for beta-catenin was detected in the membranes at the tumor center and
      in the nuclei at the invasive front. In 32 patients (26.9% of all cases), beta
      catenin was expressed exclusively in the nuclei of the carcinoma cells throughout
      the tumors. Significant differences in expression of nuclear beta-catenin in the
      primary tumors were detected between the liver metastasis and non-liver
      metastasis groups at the tumor center (p=0.004), invasive front (p=0.021) and in
      the vessels (p<0.0001). CONCLUSION: Nuclear accumulation of beta-catenin in
      cellular cells at the invasive front and in the vessels was the most powerful
      predictor of liver metastasis in colorectal cancer. This may be an important
      marker in the selection of patients for adjuvant therapy or other treatment
      modalities.

PMID- 18630469
TI  - Occult lung cancer incidentally found during surgery for esophageal and gastric
      cancer: a case report.
AB  - A 70-year-old male was admitted to our hospital because of advanced esophageal
      squamous cell carcinoma and early gastric adenocarcinoma. A esophagectomy and
      partial gastrectomy with three-field lymph node dissection (neck, mediastinum and
      abdomen) was performed. Both tumors had lymph node metastases. In addition, three
      mediastinal lymph nodes (two subcarinal lymph nodes and a middle thoracic
      paraesophageal lymph node) were involved with adenocarcinoma. To elucidate
      whether they were metastases from the gastric cancer, an immunohistochemical
      analysis was performed. The cancer cells in these lymph nodes were positive for
      cytokeratin (CK) 7 and negative for CK 20, thus suggesting metastasis from a
      nondigestive organ. Interestingly, they were positive for thyroid transcription
      factor 1 (TTF-1), indicating metastasis from a lung cancer. Since the
      preoperative computed tomographic scan showed no evidence of lung cancer, a
      diagnosis of metastases from an occult lung cancer was finally recorded. Ten
      months after surgery, the patient was alive without a recurrence or the
      appearance of a lung cancer.

PMID- 18630472
TI  - Cancer chemoprevention: a summary of the current evidence.
AB  - Cancer chemoprevention is defined as the use of natural, synthetic, or biological
      chemical agents to reverse, suppress, or prevent either the initial phase of
      carcinogenesis or the progression of neoplastic cells to cancer. At present, the
      circle of agents with an established chemopreventive effect is restricted to
      tamoxifen and raloxifene in breast cancer, finasteride in prostate cancer, and
      celecoxib in colon polyp prevention. However, in recent years, there has been an
      exponential increase in the study of agents that have a chemopreventive potential
      against cancer. In this review, the current evidence regarding cancer
      chemoprevention in major target organs is summarised, discussing the
      epidemiological as well as the experimental data.

PMID- 18630470
TI  - The perioperative morbidity of laparoscopic pelvic lymph node staging in patients
      with advanced cervical cancer.
AB  - BACKGROUND: Laparoscopic pelvic lymph node staging is widely used in patients
      with cervical cancer prior to the initiation of primary chemoradiation therapy.
      Data on the morbidity of this procedure are sparse. PATIENTS AND METHODS: Between
      1995 and 2007, 71 patients with locally advanced cervical cancer (FIGO stage IB2
      IIIB) underwent laparoscopic pelvic lymph node staging prior to primary
      chemoradiation therapy. Surgical outcome and perioperative morbidity were
      evaluated. RESULTS: The median operation time, number of resected lymph nodes and
      time between surgery and the initiation of chemoradiation therapy was 100
      minutes, 15 lymph nodes and 18 days, respectively. Intraoperatively, one
      laceration of the obturatoric artery and one bladder injury occurred. One
      procedure was converted to a laparotomy. Three short-term postoperative
      complications including one hematoma in the port side area, one umbilical suture
      insufficiency requiring a hernia reposition, and one postoperative bleeding that
      required rehospitalization were noted. Two patients with intraabdominal abscesses
      required repeat laparoscopy. Of note, three patients developed port site
      metastases during followup. CONCLUSION: Although patients experienced
      perioperative morbidity, the present study provides further evidence that,
      overall, laparoscopic pelvic lymph node staging is a relatively safe procedure
      for patients with cervical cancer.

PMID- 18630473
TI  - Better assessment of nodal metastases by PET/CT fusion compared to side-by-side
      PET/CT in oesophageal cancer.
AB  - BACKGROUND: Recently, positron emission tomography/computed tomography (PET/CT)
      has been introduced in the staging of oesophageal cancer. The impact of PET/CT
      fusion in comparison with side-by-side PET/CT in these tumours, was analyzed.
      PATIENTS AND METHODS: In 61 patients, 18-F-fluorodeoxyglucose (FDG)-PET and
      multidetector (md)-CT were performed within a two week interval. Software-fusion
      of md-CT and FDG-PET was correlated with side-by-side FDG-PET/CT reading by two
      independent investigators. The gold standard was the pathological outcome or
      clinical evidence of progression during the first year of follow-up. RESULTS: In
      18 patients (18/61; 30%), nodal staging improved with software-fusion. The number
      of nodal metastases increased in five patients and decreased in four patients,
      leading to up-staging in one patient (2%) and down-staging in three patients
      (5%). In nine cases (15%), certainty and localization of metastases improved.
      However, the number of distant metastases did not change and software-fusion did
      not have an influence on resectability. CONCLUSION: PET/CT fusion substantially
      improves detection and localization of nodal metastases and may have an impact on
      locoregional treatment options.

PMID- 18630474
TI  - The expression of matrix metalloproteinases-2 and -9 and their tissue inhibitor 2
      in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis
      and clinicopathological parameters.
AB  - AIM: To investigate the expression of metalloproteinase (MMP) -2, MMP-9 and
      tissue inhibitor of MMP (TIMP) -2 in pancreatic ductal and ampullary carcinoma
      and to test the findings for correlation with angiogenesis and several
      clinicopathological parameters. PATIENTS AND METHODS: Paraffin sections from 32
      pancreatic ductal adenocarcinomas and 17 ampullary carcinomas were assessed for
      the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemistry. Stromal and
      epithelial staining was evaluated separately. Moreover, sections stained
      immunohistochemically with anti-CD34 antibody were evaluated by image analysis
      for the quantification of microvessel density (MVD). RESULTS: In pancreatic
      ductal adenocarcinoma, lower levels of glandular TIMP-2 were found in poorly
      differentiated tumors, while high glandular TIMP-2 expression was significantly
      associated with better survival. The age of the patients and the degree of
      differentiation of the tumor were identified as independent prognostic
      parameters. No relation was found between the expression of MMPs, TIMP or
      angiogenesis and the parameters under consideration. In ampullary adenocarcinoma,
      strong expression of glandular MMP-2 was associated with higher MVD values.
      Moreover, lymph vessel invasion was associated with higher stromal TIMP-2.
      CONCLUSION: In pancreatic ductal adenocarcinoma, TIMP-2 may have a more crucial
      role in prognosis than MMP-2, MMP-9 or angiogenesis. In ampullary adenocarcinoma,
      MMP-2 expression correlated with MVD, supporting its postulated role in
      angiogenesis.

PMID- 18630471
TI  - DNA repair gene ERCC2, XPC, XRCC1, XRCC3 polymorphisms and associations with
      bladder cancer risk in a French cohort.
AB  - In polygenic diseases, association studies look for genetic variation such as
      polymorphisms in low penetrance genes, i.e. genes in interaction with
      environmental factors. DNA repair systems that protect the genome from
      deleterious endogenous and exogenous damage have been shown to significantly
      reduce activity. In particular, enzymes of the nucleotide excision repair pathway
      are suspected to be implicated in cancer. In this study bladder cancer which is
      viewed as a polygenic disease was investigated. The functional polymorphisms of
      four DNA repair genes, excision repair cross-complementing group 2 (ERCC2),
      Xeroderma Pigmentosum group C (XPC), and Xray repair cross-complementing groups 1
      and 3 (XRCC1 and XRCC3) were analyzed. The studied population included 51 bladder
      cancer cases and 45 controls. The genotyping of six SNP (single nucleotide
      polymorphism) was carried out on these populations with the MGB (Minor Groove
      Binder) probe technique which uses allelic discrimination with the Taqman method.
      The Gln allele of the XPC 939 polymorphism was found to be associated with an
      increase in bladder cancer risk.

PMID- 18630475
TI  - Accuracy of a new echographic method (RULES, radiofrequency ultrasonic local
      estimators) in prostate cancer diagnosis.
AB  - BACKGROUND: This study evaluated the accuracy of a new echographic method named
      RULES (radiofrequency ultrasonic local estimators) in the diagnosis of prostate
      cancer. PATIENTS AND METHODS: A double-blind prospective study was carried out on
      105 patients mean age 66.6 years, prostate specific antigen (PSA) >4 ng/ml with
      clinical and/or biochemical suspicious of prostate cancer. Patients were
      submitted to transrectal prostate biopsy (8 to 12 cores) using a traditional
      echograph connected to a new hardware/ software platform named FEMMINA (fast
      echographic multiparameter multi image novel apparatus) that processes the echo
      signal by a RULES (radiofrequency ultrasonic local estimators) algorithm.
      Histological findings were compared to B-mode and RULES modality. RESULTS: Cancer
      was detected in 32/105 patients, of which 26/32 were determined as positive with
      the RULES method. RULES had better positive predictive value, negative predictive
      value, sensitivity, specificity and accuracy than B-mode. CONCLUSION: Results
      obtained with RULES are encouraging and, if further confirmed, could help to
      reduce the number of unnecessary prostatic biopsies.

PMID- 18630477
TI  - Local reactions to treatments with Viscum album L. extracts and their association
      with T-lymphocyte subsets and quality of life.
AB  - BACKGROUND: In a previous study a decline of T-lymphocyte function was observed
      within a 6-month period of Viscum album extract (VA-E) application which did not
      occur in those patients with dose adaptation in response to strong local
      reactions (LR) or in those with moderate LR. To further investigate the
      immunological prerequisites of these differences in the VA-E susceptibilities, an
      analysis was carried out of the pre-existing differences in the tumor patients'
      lymphocyte subsets, and of whether the LR pattern (none, moderate, strong) might
      be associated with distinct aspects of the patients' quality of life. PATIENTS
      AND METHODS: Seventy-one cancer patients were subcutaneously treated with VA-E
      (Iscador) at increasing concentrations and their lymphocyte subsets measured by
      flowcytometry during a 6 month observation period; quality of life was assessed
      with the HLQ questionnaire. RESULTS: The occurrence of stronger LR was associated
      with a primarily higher level of T-cells and their CD4+ T-helper/inducer subset,
      and CD25+ respectively HLA-DR+ (activated) T-cells. Moreover, counts or
      proportions of T-cells, CD4+ T-helper/inducer cells and CD8+ CD28+ cytotoxic
      cells were lower, while the relative proportions of CD8+ CD28- suppressor cells,
      B- and NK-cells were the highest in the group with moderate LR. In particular,
      this latter group had a significantly higher quality of life. CONCLUSION: Our
      results indicate that the induction of moderate LR in response to VA-E
      application was associated with better T cell function and quality of life.
      Extracts from Viscum album (VA-E) are widely used as a

PMID- 18630476
TI  - Weekly cisplatin, infusional high-dose 5-fluorouracil and leucovorin for
      advanced, recurrent and metastatic cervical carcinoma.
AB  - BACKGROUND: To evaluate the effectiveness and toxicity of infusional cisplatin
      and weekly 24-hour infusion of high-dose fluorouracil plus leucovorin (P-HDFL)
      for the treatment of patients with stage IVB, recurrent and metastatic carcinoma
      of the cervix. PATIENTS AND METHODS: A phase II study of P-HDFL in stage IVB,
      recurrent and metastatic carcinoma of cervix was initiated in January 2001. As of
      March 2007, a total of 21 patients were enrolled. Of these, 16 were evaluable for
      response. RESULTS: The overall objective response rate was 25% [95% confidence
      interval (CI), 1.2-48.8%] with none achieving complete response. The median
      progression-free survival and overall survival for all 21 patients was 2.3 months
      (95% CI, 1.2-4.3 months) and 10.5 months (95% CI, 4.6-17.4 months), respectively.
      Toxicity was tolerable. The main problems were nausea/vomiting and anemia.
      CONCLUSION: P-HDFL appears to be a moderately effective regimen with low toxicity
      for treating patients with advanced, recurrent and metastatic cervical cancer.

PMID- 18630479
TI  - Prognostic significance of fascin expression in advanced poorly differentiated
      serous ovarian cancer.
AB  - BACKGROUND: High expression of the actin-bundling protein fascin correlates well
      with histological grade and clinical stage of ovarian carcinoma. This study
      addresses fascin expression in advanced poorly differentiated serous ovarian
      cancer with respect to progression free interval (PFI) and overall survival.
      PATIENTS AND METHODS: Fascin and Ki-67 expression were analysed in paraffin
      blocks tissue sections of 56 stage III, poorly differentiated (G3) serous
      adenocarcinoma patients by immunohistochemistry. Fascin expression was tested for
      correlation with PFI and overall survival. RESULTS: Fascin expression inversely
      correlated with Ki-67 expression (p=0.016). Strong fascin immunoreactivity was
      associated with poor prognosis; patients with low fascin expression had a median
      survival of 36.5 months versus 32 months for high fascin expression (p=0.041),
      and the median PFI was 24 versus 17.5 months (p=0.034). CONCLUSION: Fascin
      expression is an independent prognostic factor for survival of advanced ovarian
      serous carcinoma, and may represent a novel therapeutic target for patients with
      aggressive forms of ovarian cancer.

PMID- 18630480
TI  - Assessing polyp size by improved digitalized computed tomography (CT).
AB  - BACKGROUND: The size of colorectal polyps is important in the clinical management
      of these lesions. When using a conventional ruler (the tool of pathologists
      worldwide), we have previously found unacceptably high intra- and inter-observer
      variations in assessing the size of phantom polyps. The aim of this study was to
      assess the size of 12 phantom polyps by computed tomography (CT). MATERIALS AND
      METHODS: The size of phantom polyps as assessed by CT was compared to the gold
      standard size (GSS) measured at The Royal Institute of Technology, Stockholm,
      Sweden. RESULTS: In 33.3% (n=4) of the 12 polyps and in 41.7% (n=25) of the 60
      measurements, the mean CT size under- or overestimated the GSS by more than 1 mm.
      In 15%, or in 9 of the 60 measurements, the CT size was under- or overestimated
      by more than 2 mm. In polyp #5 the GSS size was 8.41 mm where the expected cancer
      risk in adenomas is 1%. But 3 out of 5 CT measurements were >10 mm, where the
      expected cancer-risk in adenomas is 10%. In polyp #10 the GSS size was 10.20 mm
      where the expected cancer-risk is 10%. But 2 out of 5 CT measurements were <10 mm
      where the expected risk is only 1%. CONCLUSION: The size assessed by CT was more
      reliable than that obtained with a millimetre ruler using the same devices,
      inasmuch as the disparate individual deviation-values found with the latter
      method were avoided. The volume and the shape of the devices influenced size
      assessment of phantom polyps by CT.

PMID- 18630478
TI  - Clinical efficacy of proton magnetic resonance spectroscopy (1H-MRS) in the
      diagnosis of localized prostate cancer.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy of proton
      magnetic resonance spectroscopy (1H-MRS) in the detection of prostate cancer.
      MATERIALS AND METHODS: The experimental group consisted of 20 patients with
      localized prostate cancer who underwent radical prostatectomy. The sensitivity,
      positive predictive value and accuracy of the detection of prostate cancer in the
      12 sections of the peripheral zone were calculated for prostate biopsy alone, 1H
      MRS alone and the combination of these methods, respectively. RESULTS: The
      sensitivity, the positive predictive value, and the accuracy of the preoperative
      diagnosis of prostate cancer were 43.7%, 68.9% and 54.6%, respectively, with
      prostate biopsy alone; 60.6%, 87.8% and 71.4% with 1H-MRS alone; and 88.7%, 88.7%
      and 87.4% with the combination of biopsy and 1H-MRS, respectively. Combined use
      of biopsy and 1H-MRS significantly improved the sensitivity, positive predictive
      value and accuracy of the diagnosis. CONCLUSION: 1H-MRS together with biopsy
      might improve the diagnostic accuracy in prostate cancer.

PMID- 18630481
TI  - GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal
      cancer.
AB  - BACKGROUND: Cancer of the colorectal region is the second most frequent cause of
      death among malignant diseases. The influence of two allelic polymorphisms of
      GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated.
      PATIENTS AND METHODS: Intraoperatively removed tissue samples were processed from
      colorectal cancer patients. Cancer-free human samples were used as matched
      controls. Samples were digested with proteinase-K. DNA solution was used for PCR
      amplification. RESULTS: No significant difference was found between tumor
      patients and controls in the investigated polymorphisms. A significant
      association was found in Dukes' B stage patients between the GSTM1 and p53 gene
      variants and survival. In patients with GSTM1 null genotype and p53 Arg/Pro
      heterozygotes or Pro/Pro homozygotes the chance of survival is significantly
      lower than in the case of GSTM1+ and p53 Arg/Arg variants (p=0.009 and p=0.008,
      respectively). CONCLUSION: The significance of the investigated polymorphisms in
      prognosis is dependent on the tumor stage. These parameters might be used in
      certain cases as prognostic biomarkers in clinical diagnostics and in the
      planning of individual therapy.

PMID- 18630482
TI  - Irinotecan plus capecitabine as first-line chemotherapy in advanced colorectal
      cancer.
AB  - Capecitabine, an oral 5-fluorouracil (5-FU) prodrug, is increasingly replacing
      intravenous i.v. 5-FU/leucovorin in colorectal cancer treatment. THE AIM of this
      study was to evaluate efficacy and safety of the combination chemotherapy of
      irinotecan plus capecitabine (XELIRI), in patients with advanced colorectal
      adenocarcinoma. PATIENTS AND METHODS: Forty patients received first-line
      chemotherapy with capecitabine (1.000 mg/m2 twice daily) on days 1-14 and
      irinotecan (240 mg/m2) on day 1 of a 21-day cycle. Baseline characteristics: 24
      men, 16 women; median age 64.5 years. Most common metastatic sites were the liver
      (55%), lymph nodes (45%), lung (22.5%) and bones (17.5%). RESULTS: There were 12
      partial responses (30%), 11 cases of stable disease (27.5%), and 17 cases of
      disease progression (42.5%). The median survival was 16 months (range, 6-26
      months) and median progression-free survival was 7 months (range, 3-14 months).
      Frequently encountered therapy-related events were leukopenia and
      gastrointestinal side effects including diarrhea. CONCLUSION: XELIRI is a well
      tolerated regimen, with an activity comparable to, but more convenient than,
      irinotecan-5-FU i.v. combinations in patients with previously untreated advanced
      colorectal cancer.

PMID- 18630485
TI  - Brain metastases in relapsed epithelial ovarian cancer after chemotherapy with
      pegylated liposomal doxorubicin.
AB  - BACKGROUND: Brain metastases in epithelial ovarian cancer (EOC) occur rarely and
      are associated with a poor prognosis. No significant risk factors have been
      identified and no evidence-based treatment guidelines are currently available.
      CASE REPORT: A 56-year-old EOC patient presented with seizure at the Emergency
      Department eleven days after completion of fourth-line chemotherapy with
      pegylated liposomal doxorubicin (PLD). A computed tomography (CT) scan revealed
      multiple metastases. The patient received radiotherapy with a total dose of 30.8
      Gy and 8 cycles of paclitaxel resulting in stable disease. Based on the current
      literature, treatment options are discussed. CONCLUSION: Therapeutic options for
      brain metastases include radiation, systemic or intrathecal chemotherapy, surgery
      or a combination regime. Since the effectiveness of systemic chemotherapy remains
      controversial, current research focuses on developing new anticancer drugs that
      penetrate the blood-brain barrier in order to prevent and/or treat brain
      metastases.

PMID- 18630484
TI  - Diminishing impact of preoperative carcinoembryonic antigen (CEA) in prognosis of
      Dukes' C colorectal cancer.
AB  - BACKGROUND: In curable colorectal cancer (CRC), preoperative serum
      carcinoembryonic antigen (CEA) (preCEA) has been reported to have predictive
      prognostic value. However, data remains insufficient to support its clinical use.
      The aim of the current study was to validate the prognostic impact of preCEA in
      Dukes' C CRC. PATIENTS AND METHODS: The prognostic significance of preCEA for 237
      Dukes' C CRC patients assessed retrospectively (between 1990 and 2000: previous
      cases) and the prospective relevance for 197 counterparts (between 2001 and 2004:
      recent cases) according to preCEA, were both examined. RESULTS: The previous
      cases showed the most potent impact of preCEA as an independent prognostic factor
      (hazard ratio=2.0, p=0.003) among the clinicopathological factors using a
      multivariate proportional hazard model, while the recent cases did not even show
      a univariate prognostic impact. A significant difference in the prognosis between
      the two periods was only found in the patients with elevated preCEA administered
      adjuvant chemotherapy (ADT) (p=0.03). Between the two terms, a dramatic change of
      ADT regimens from 5FU alone (p<0.001) to 5FU in combination with leucovorin
      (p<0.001) and/or irinotecan (p-0.0009/0.005) was introduced, and N2 patient
      survival was dramatically improved. However, a significant prognostic difference
      for the elevated preCEA patients with ADT could not be demonstrated by sub
      analysis of N1 and N2 disease due to diminished correlation of preCEA and the N
      factor (p=0.02 to 0.5), indicating that preCEA did not predict chemosensitivity.
      CONCLUSION: The preCEA is no longer useful in predicting prognosis with Dukes' C
      CRC patients, because of the loss of preCEA association with the N factor,
      putatively through undefined diagnostic or therapeutic advancement.

PMID- 18630483
TI  - Prognostic impact of combined fludarabine, treosulfan and mitoxantrone resistance
      profile in childhood acute myeloid leukemia.
AB  - BACKGROUND: The role of cellular drug resistance in childhood acute myeloid
      leukemia (AML) has not yet been established. The aim of the study was the
      analysis of the clinical value of ex vivo drug resistance in pediatric AML.
      PATIENTS AND METHODS: A cohort of 90 children with de novo AML were assayed for
      drug resistance profile by the 3-4,5-dimethylthiazol-2-yl-2,5-difenyl tetrazolium
      bromide (MTT) assay and prognostic model of in vitro drug sensitivity was
      analyzed. RESULTS: Children who relapsed during follow-up showed higher in vitro
      resistance of leukemic blasts to most of the drugs tested, except for cytarabine,
      cladribine, vincristine, mercaptopurine and thioguanine. A combined in vitro drug
      resistance profile to fludarabine, treosulfan and mitoxantrone (FTM score) was
      defined and it had an independent prognostic significance for disease free
      survival in pediatric AML. CONCLUSION: The combined fludarabine, treosulfan and
      mitoxantrone resistance profile to possibly may be used for better stratification
      of children with AML or indicate the necessity for additional therapy.

PMID- 18630486
TI  - Impact of preoperative hemoglobin level on survival of non-small cell lung cancer
      patients.
AB  - BACKGROUND: Only a few studies have reported any prognostic impact of the
      preoperative hemoglobin level itself in resectable non-small cell lung cancer
      (NSCLC). The survival impact of preoperative hemoglobin level and the
      relationship between hemoglobin and serum CEA level were investigated. PATIENTS
      AND METHODS: Two hundred and forty consecutive NSCLC patients were reviewed
      retrospectively. RESULTS: The 5-year survival of patients with low and those with
      a normal hemoglobin level was 42.99% and 73.47%, respectively. Both univariate
      and multivariate analyses indicated the independent prognostic impact of the
      hemoglobin level. The result for stage I patients was identical. Patients with
      normal hemoglobin could be subdivided into 2 groups based on their serum CEA
      level; the 5-year survival of patients with normal and those with elevated CEA
      was 81.72% and 57.24%, respectively. CONCLUSION: The preoperative hemoglobin
      level was a prognostic factor for NSCLC patients. The combined use of hemoglobin
      and CEA levels might be useful to predict the prognosis of patients.

PMID- 18630490
TI  - [The assessment of concordance of triage codes in an emergency department].
AB  - AIM: The triage forms filled in 2006 by nursing personnel dedicated to the triage
      in an Emergency Department were analysed. METHODS: The 37.323 triage forms were
      scrutinized to identify any discrepancies in severity codes assigned by the nurse
      and by the medical doctor, after the clinical and instrumental assessment.
      RESULTS: Four-hundred-forty discrepancies were identified (13% of those initially
      classified as discrepancies): 221 (50.2%) severity codes were overestimated and
      219 underestimated. The percentage of discrepancies increased during night hours
      and at the morning shift change. Nurses who performed the triage less often, made
      an higher number of over or underestimates. Overall, the number of discrepancies
      was 0.5 per shift. CONCLUSIONS: The overall performance can be considered very
      good. A model for analysis of discrepancies can be proposed. A number of
      proposals have been advanced to further improve the nurses performance.

PMID- 18630488
TI  - An ecological study of cancer mortality rates including indices for dietary iron
      and zinc.
AB  - BACKGROUND: Dietary iron and zinc affect the risk of cancer, with dietary iron
      generally correlated with increased risk and dietary zinc with reduced risk.
      However, zinc supplements have been found correlated with increased risk of
      cancer. PATIENTS AND METHODS: An ecological study was conducted using state
      averaged cancer mortality rate data for white Americans for 1970-94 with indices
      for alcohol consumption, smoking, Hispanic heritage, and urban residence plus
      dietary factors for four large U.S. regions. RESULTS: The dietary zinc index was
      inversely correlated with 12 types of cancer, whereas the dietary iron index was
      directly correlated with 10 types of cancer which correlated with both iron
      directly and zinc inversely were bladder, breast, colon, esophageal, gastric,
      rectal cancer, and Hodgkin's lymphoma; those inversely with zinc only were
      laryngeal, nasopharyngeal, oral, skin and vulvar cancer. Solar UVB was inversely
      correlated with 10 of the 15 types of cancer for which the iron and/or zinc
      indices had significant correlations, the smoking and urban indices with nine,
      and the alcohol index with eight. CONCLUSION: Although there are mechanisms that
      explain why zinc should reduce the risk of cancer, whereas iron should increase
      the risk, these indices may represent the dietary sources of these nutrients,
      e.g. whole grains for zinc and red meat for iron, and other components of these
      dietary factors.

PMID- 18630487
TI  - Free-from-progression period and overall short preoperative immunotherapy with IL
      2 increases the survival of pancreatic cancer patients treated with
      macroscopically radical surgery.
AB  - BACKGROUND: The treatment of pancreatic cancer is still rudimentary, even in the
      case of locally limited tumors, because of the high frequency of recurrence due
      to severe suppression of the anticancer immunity that is further amplified by
      surgery-induced immunosuppression, evidenced by a decline in lymphocyte numbers
      during the postoperative period. Previous studies in colorectal cancer
      demonstrated that surgery-induced lymphocytopenia may be abrogated by a brief
      preoperative administration of IL-2. MATERIALS AND METHODS: The study included 30
      consecutive patients who were randomized to be treated by radical surgery alone
      as a control group or by a preoperative immunotherapy with IL-2 (12 MIU/day SC
      for 3 consecutive days) plus surgery. RESULTS: Mean lymphocyte numbers
      significantly decreased in patients treated with surgery only, whereas it
      significantly rose in the IL-2-treated group. After a follow-up of 36 months,
      both the free-from-progression period (FFPP) and the overall survival were
      significantly higher in patients treated with IL-2. CONCLUSION: These preliminary
      results suggest that a short-period preoperative immunotherapy with IL-2 is
      sufficient to modify host tumor interactions in operable pancreatic cancer, with
      a subsequent abrogation of postoperative lymphocytopenia and a prolongation of
      FFPP and overall survival time.

PMID- 18630491
TI  - [Assessment of a nursing protocol for the management of hyperglicaemia in
      hospitalized patients].
AB  - AIM: To assess the effectiveness of a nurse-led protocol for the management of
      hypo/ hyperglicaemia in a medical ward. METHODS: Protocols for standard therapy,
      and parenteral intensive insulin therapy for severe hypo/hyperglycaemia in
      hospitalised patients were implemented. PERIOD: march-november 2007. RESULTS: 189
      patients (19%) were labelled as "hyperglycaemic" at admission in Emergency
      Department. Median (+/-IQR) age was 77 (70-84) years, 41% were men, with known
      diabetes 74%, 18% had skin ulcers. Median glycaemia at admission was 144.5 (98
      220) mg/dl. Thirty-six percent of patients was euglycaemic (60-126 mg/dl), 3%
      hypoglycaemic (<60 mg/dl). The glicaemic values ranged from 127-140 mg/dl (9%
      patients), from 141-280 mg/dl, (40%patients) and > 280 mg/dl (12% patients). The
      glicaemic values of the 14 patients requiring the intravenous intensive insulin
      regimen remained in a safe range (80-250 mg/dl) in the first 15 hours from the
      infusion start. No patient experienced a life-threatening hypoglycaemia nor
      hypoglycaemic coma. After three days on standard therapy, glicaemic levels were
      acceptable: 142 (98-185) pre-breakfast, 144(107-200) pre-lunch, 131 (102-190) pre
      dinner, 183 (123-230) mg/dl postprandial. CONCLUSION: Data showed the
      effectiveness and safety of a nurse-led protocol for the care of hyperglicaemia
      in a medical ward.

PMID- 18630489
TI  - [Rainbows and poetry workshops].

PMID- 18630492
TI  - [A survey and childhood deafness in a neonatology unit of Caritas Baby Hospital
      in Bethlehem].
AB  - AIM: The prevalence of deafness in a pediatric hospital Caritas Baby Hospital in
      Bethlehem was described. METHOD: All the clinical records of neonates born
      September 25, 2006 to March 25, 2007 screened for deafness were selected.
      RESULTS: Among the 274 screened newborns, 112 were females and 162 males, 97%
      from the districts of Bethlehem and Hebron, and 3% from other locations in the
      West Bank. The most recurrent diagnoses were jaundice, potential sepsis and
      prematurity. Sixty-three were positive at the first screening, 26 at the second
      screening and only 4 were visited by the audiologist, who confirmed a hearing
      loss (medium or high) in 3 newborns. CONCLUSIONS: Screening for deafness should
      be extended to all newborns and parents should be educated increase awareness of
      potential problems of children and to refer the child to a specialist.

PMID- 18630493
TI  - [Are antipsychotics safe in the management of demented patients?].

PMID- 18630494
TI  - [Medication errors at home: risks related to parental administration of
      paediatric drugs and strategies for prevention].

PMID- 18630495
TI  - [A dialogue between a meridian and a traveller].

PMID- 18630496
TI  - [It would be sad without the rainbow. Poems of children with cancer].

PMID- 18630500
TI  - IFN-y enhances T(H)1 polarisation of monocyte-derived dendritic cells matured
      with clinical-grade cytokines using serum-free conditions.
AB  - Using serum-free conditions, human monocyte-derived dendritic cells (MoDCs) tend
      to mature insufficiently in a T(H)1-polarizing direction under approved and
      standardized clinical conditions. However, for the initiation of an efficient
      tumour antigen-specific cytotoxic T-cell response, the induction of a distinct
      T(H)1 response is favourable. Therefore, to improve T(H)1 polarisation, the
      influence of interferon-gamma (IFN-gamma) on the maturation of MoDCs was
      investigated with clinical-grade cytokines or lipopolysaccharide (LPS) in serum
      free medium focusing on the viability, phenotypic characteristics, cytokine
      profile and restimulating capacities. As in previous research, we confirmed that
      in respect of viability and phenotypic characteristics, cytokine cocktails
      consisting of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta,
      IL-6 and prostaglandin (PG) E2, mature MoDCs most efficiently. However, these
      cytokine-matured MoDCs secreted relatively high levels of IL-10 and only low
      levels of IL-12p70. Remarkably, if IFN-gamma was added, significantly lower
      levels of IL-10 concomitant with higher levels of IL-12p70 could be detected.
      Pretreatment with IFN-gamma did not improve the phenotypic characteristics nor
      the T(H)1 polarisation of MoDCs. Nevertheless, MoDCs matured with clinical-grade
      cytokines and IFN-gamma could be re-stimulated most effectively with IFN-gamma.
      In conclusion, our work demonstrates that addition of INF-gamma to clinical-grade
      cytokine cocktails readily matures MoDCs and enhances their T(H)1 polarisation
      efficiently under serum-free conditions.

PMID- 18630503
TI  - Mammaglobin and lipophilin B expression in breast tumors and their lack of effect
      on breast cancer cell proliferation.
AB  - BACKGROUND: Mammaglobin (SCGB2A2) and lipophilin B (SCGB1D2) are members of the
      secretoglobin polypeptide family. Mammaglobin has been shown to be overexpressed
      in breast tumor tissue, indicating that mammaglobin might confer a growth
      advantage to mammaglobin-expressing tumor cells. MATERIALS AND METHODS: The
      mammaglobin and lipophilin B mRNA expression levels were investigated in seven
      breast tumors and matched nonneoplastic tissues from the same patients using
      quantitative real-time RT-PCR. The effect of mammaglobin and lipophilin B
      expression on breast cancer cell proliferation rates was investigated by
      analyzing retrovirally transduced Hs578T cell clones. Cell proliferation rates
      were determined during the exponential growth phase by analyzing the change in
      lactate dehydrogenase activity over time. RESULTS: All analyzed breast cancer
      tumors had lower expression levels of mammaglobin and lipophilin B than the
      respective mean level of the nonneoplastic breast tissues; no prominent
      overexpression was evident. There was high variability in the expression of
      mammaglobin and lipophilin B among the non-neoplastic samples, showing that
      caution should be taken when evaluating their over- and underexpression in
      tumors. The expression levels of mammaglobin and lipophilin B correlated with
      each other in the analyzed samples (p = 0.001). Ectopic overexpression of
      mammaglobin and lipophilin B did not affect the cell proliferation rate of Hs578T
      breast carcinoma cells in vitro. CONCLUSION: Our findings suggest that the
      overexpression of mammaglobin observed in certain breast tumors is an
      epiphenomenon not causally involved in breast carcinogenesis.

PMID- 18630501
TI  - 5-Fluorouracil-related gene expression in primary sites and hepatic metastases of
      colorectal carcinomas.
AB  - The aim of this study was to investigate the correlation of the mRNA expressions
      of 5-fluorouracil (5FU)-related genes in the primary sites and liver metastases
      of colorectal carcinomas. PATIENTS AND METHODS: Patients with liver metastases
      from colorectal carcinomas were included (n = 43). The expression ratios to beta
      actin of mRNA of thymidine synthase (TS), dihydropyrimidine dehydrogenase (DPD),
      thymidine phosphorylase (TP) and oroteta phosphoribosyl transferase (OPRT) were
      measured in primary and liver metastases of colorectal carcinomas by laser
      captured microdissection and real time PCR. RESULTS: The ratios for the
      expression of TS, DPD, TP and OPRT mRNAs were significantly correlated between
      paired primary sites and liver metastases. The mRNA expression ratios of DPD and
      TP showed a significant correlation both in primary sites and in liver
      metastases. CONCLUSION: Enzymes of the primary colorectal carcinomas can be used
      in predicting the therapeutic efficacy of 5FU against liver metastases.

PMID- 18630499
TI  - Invasion front-specific overexpression of tissue inhibitor of metalloproteinase-1
      in liver metastases from colorectal cancer.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors, the tissue
      inhibitors of metalloproteinases (TIMPs), have been implicated in invasion and
      metastasis. The distribution of MMPs and TIMPs in the invasion front of liver
      metastases from colorectal cancer were investigated in order to understand their
      potential role in invasiveness. MATERIALS AND METHODS: Freshly frozen material of
      colorectal metastases of the liver was microdissected into four separate
      compartments, namely pure liver, liver invasion, tumour invasion and pure tumour.
      RNA was isolated and analyzed on Affymetrix microarrays. Expression of TIMP-1 was
      confirmed by quantitative polymerase chain reaction in 10 colorectal liver
      metastases. Cellular localisation of TIMP-1 was examined by immunohistochemistry.
      RESULTS: Affymetrix microarray data revealed that several MMP and TIMP genes
      including MMP-2, -3, -7, -9, -11, -12, -14, -15, -16, -19 and -24, and TIMP-1, -2
      and -3 were generally up-regulated in both invasion front compartments. Among
      these genes, TIMP-1 showed the highest expression. The qPCR results indicated an
      average 15-fold upregulation of TIMP-1 in the liver invasive front and an average
      13-fold up-regulation in the tumor invasive front, each compared to normal liver
      tissue. Immunohistochemistry revealed expression of TIMP-1 in tumour epithelia as
      well as in host tissue cells, including fibroblastic cells. CONCLUSION: Our data
      indicate that tumour invasion in colorectal liver metastasis is associated with
      increased TIMP-1 RNA and protein levels in both tumour and host cells.

PMID- 18630498
TI  - The antitumor effect of liposome-encapsulated cisplatin on rat osteosarcoma and
      its enhancement by caffeine.
AB  - BACKGROUND: Drug delivery systems are for the purpose of targeting a drug to a
      specific tissue selectively and at the same time preventing a drug from
      accumulating in healthy organs. Liposomes have been proposed as useful drug
      carriers in targeted drug delivery system and are under investigation in several
      therapeutic fields. Caffeine has been identified as belonging to the group of
      xanthines that enhances the action of cisplatin. MATERIALS AND METHODS: In this
      study, liposomes containing polyethylene glycol encapsulated cisplatin (CDDP-L)
      were prepared. The action of CDDP-L on rat osteosarcoma and the enhancing action
      of caffeine on the antitumor effect of CDDP-L were evaluated. Using osteosarcoma
      bearing rats, the retention of CDDP-L in the blood, its intratumor concentration,
      cytoreductive effect and the enhancing action of caffeine on its antitumor effect
      were examined. RESULTS: The liposomes were able to remain in the systemic
      circulation for a long time and to be concentrated in the osteosarcoma, but that
      action did not produce an effect corresponding to the quantity of cisplatin which
      was encapsulated reaching the tumor. In rats administered CDDP-L, it was
      discovered that the antitumor effect was not only enhanced by the
      coadministration of caffeine but also further enhanced when the dosing period of
      caffeine was increased. CONCLUSION: CDDP-L combined with caffeine treatment can
      produce better results for osteosarcoma.

PMID- 18630497
TI  - Role of Puralpha in the modulation of homologous recombination-directed DNA
      repair by HIV-1 Tat.
AB  - BACKGROUND: The nucleic acid-binding protein Puralpha is involved at stalled DNA
      replication forks, in double-strand break (DSB) DNA repair and the cellular
      response to DNA replication stress. Puralpha interacts with HIV-1 Tat, which
      regulates homologous recombination-directed DNA repair (HRR). MATERIALS AND
      METHODS: We investigated Rad51 and HRR regulation in mouse embryo fibroblasts
      (MEFs) from PURA -/- knockout mice that lack Puralpha. RESULTS: Rad51 was induced
      in PURA -/- MEFs but was repressed when Puralpha was ectopically expressed in
      these cells. Similarly Rad51 inversely correlated with the level of Puralpha in
      normal postnatal mouse brain. HIV-1 Tat stimulated HRR DNA repair of I-SceI
      induced DNA DSBs and the nuclear appearance of Rad51 foci. In contrast, Puralpha
      suppressed HRR DNA repair, Rad51 expression, and Rad51 foci formation.
      CONCLUSION: Tat stimulates the Rad51 promoter involving both Puralpha-dependent
      and Puralpha-independent mechanisms. Interaction between Puralpha and Tat may
      have opposing effects on Rad51 expression. The effects on HRR may contribute to
      HIV-1 associated pathogenesis.

PMID- 18630502
TI  - A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and
      STX140.
AB  - This study characterises two recently developed anticancer agents in vitro and in
      vivo, 2-methoxyoestra-1,3,5(10), 16-tetraene-3-carboxamide (IRC-110160) and
      STX140. MATERIALS AND METHODS: Hormone-dependent (MCF-7), hormone-independent
      (MDA-MB-231) and P-glycoprotein overexpressing (MCF-7Dox) cells were used for
      proliferation experiments. For the tumour efficacy studies, female nude mice were
      inoculated with MDA-MB-231 cells. RESULTS: IRC-110160 is a potent inhibitor of
      both MCF-7 and MDA-MB-231 cell proliferation. Furthermore, the potency of IRC
      110160 was unaffected by the over-expression of the P-glycoprotein drug efflux
      pump. IRC-110160 and 2-methoxyoestradiol-3,17-O,O-bis-sulfamate (STX140) induced
      apoptosis in a similar timeframe in the MDA-MB-231 cell line, but only STX140
      caused G2/M arrest in these cells. In the MDA-MB-231 xenograft model 300 mg/kg
      p.o. (daily) of IRC-110160 and 20 mg/kg p.o. STX140 (daily) both completely
      inhibited tumour growth; however some toxicity was observed with IRC-110160.
      After 28 days of daily dosing STX140 (20 mg/kg p.o.) had minimal effect on the
      white blood population of mice with tumours. The masking of STX140 from white
      blood cells may be due to its interaction with carbonic anhydrase II (CAII) in
      the red blood cells. In contrast to STX140, IRC-110160 does not inhibit CAII.
      These studies highlight the activity of two orally bioavailable anti-cancer
      agents one of which, STX140, may offer a significant clinical advantage over
      existing drugs as a common dose limiting factor, haemotoxicity, may be minimised.

PMID- 18630504
TI  - Interferon-alpha restitutes the chemosensitivity in pancreatic cancer.
AB  - BACKGROUND: Multidrug resistance is a major obstacle in the treatment of
      pancreatic cancer. Immunochemotherapy including interferon-alpha increases
      response rates and survival. MATERIALS AND METHODS: Pancreatic cancer was induced
      in an orthotopic mouse model. Animals received standard chemotherapy or
      combinative treatment with interferon-alpha. Expression and function of drug
      resistance proteins were analyzed. Immunological phenotyping, cytotoxic activity
      assays and analysis of T-cell activation status were performed. RESULTS: Addition
      of interferon-alpha to chemotherapeutic regimes significantly reduced
      chemotherapy-induced expression of multidrug resistance proteins and drug efflux
      activity of cancer cells. Tumor size and metastatic seeding decreased
      significantly upon combination therapy and survival was prolonged. A
      significantly higher proportion of activated and cytotoxic active CD8+ tumor
      infiltrating lymphocytes was detectable after induction of drug resistance.
      CONCLUSION: Restitution of chemosensitivity by the addition of interferon alpha
      to chemotherapy was demonstrated in experimental pancreatic cancer for the first
      time. Since drug-resistance proteins may function as tumor antigens, our data
      support immunochemotherapy as an encouraging new approach.

PMID- 18630505
TI  - IGF-I receptor inhibition combined with rapamycin or temsirolimus inhibits
      neuroblastoma cell growth.
AB  - BACKGROUND: Neuroblastoma is the third most common solid tumor in children.
      Treatment continues to be challenging. The pathogenesis of neuroblastoma has been
      related to expression of the type 1 insulin-like growth factor receptor (IGF1R)
      and to transcription factor MYC-N amplification. Previous studies have shown that
      MYC-N expression is disrupted by blockade of the IGF1R with a specific monoclonal
      antibody, alphaIR3. Inhibition of IGF1R signaling can be accomplished by other
      agents, including rapamycin or temsirolimus, which target mTOR (mammalian target
      of rapamycin). MATERIALS AND METHODS: BE-2(c) and IMR-32 neuroblastoma cell lines
      were treated with varying concentrations of alphaIR3, rapamycin and temsirolimus
      alone or in combination and the viable cells were counted. RESULTS: Blockade of
      IGF1R signaling significantly inhibited cell growth as compared to untreated
      controls (p < 0.05), and a combination of agents was more effective than each
      agent alone. CONCLUSION: The combination of rapamycin or temsirolimus with
      alphaIR3 blocks the IGF1R signaling pathway and has an antiproliferative effect
      on neuroblastoma cells warranting further investigations using inhibitors of
      IGF1R signaling as novel combination therapy for neuroblastoma.

PMID- 18630506
TI  - Inhibition of steroid sulphatase activity via the percutaneous route: a new
      option for breast cancer therapy.
AB  - Steroid sulphatase (STS) inhibitors have been developed primarily for the
      treatment of hormone-dependent breast cancer, but may also have utility for the
      treatment of a number of androgen-dependent skin conditions. STS regulates the
      hydrolysis of steroid sulphates, such as oestrone sulphate (E1S) and
      dehydroepiandrosterone sulphate, (DHEAS). Liberated oestrone (E1) can be
      converted to biologically active oestradiol (E2) while dehydroepiandrosterone
      (DHEA) can undergo reduction to testosterone or aromatisation to E1. In this
      study the ability of the STS inhibitor STX64 (BN83495) and its N,N-dimethyl
      analogue (STX289) to inhibit liver and skin STS when applied orally or topically
      to nude mice was examined. Oral administration at 1 and 10 mg/kg resulted in
      almost complete inhibition of skin and liver STS. When applied topically to the
      dorsal neck region at 1.0 and 10 mg/kg not only skin but, unexpectedly, also
      liver STS was effectively inhibited. An investigation into the metabolism of
      these two compounds by HepG2 liver carcinoma cells, with high-performance liquid
      chromatography (HPLC) analysis, was also undertaken. In the presence of HepG2
      cells a similar degree of desulphamoylation of STX64 (68%) or de-N, N
      dimethylsulphamoylation of STX289 (66%) occurred over a 3h period. In the absence
      of cells, however, STX289 was resistant to de-N, N-dimethylsulphamoylation
      whereas STX64 was completely desulphamoylated, demonstrating the more favourable
      pharmaceutical profile of STX289 for development for topical application. It is
      concluded that both STX64 and STX289 are not only effective inhibitors of skin
      STS, but also liver STS when applied topically. These findings suggest that it
      may be possible to develop a formulation for the percutaneous administration of
      STS inhibitors, but also that this class of compound may have therapeutic
      potential for the treatment of a number of skin disorders.

PMID- 18630507
TI  - Up-regulation of survivin mRNA might be a marker for non-invasive detection of
      non-small cell lung cancer rather than for prognosis.
AB  - BACKGROUND: Survivin suppresses programmed cell death and regulates cell
      division. To evaluate the prognostic importance of the apoptosis inhibitor
      survivin for non-small cell lung cancer (NSCLC), a study was performed in 64
      patients with R0 resections for NSCLC and histopathological stages I-IIIA.
      PATIENTS AND METHODS: Analysis of survivin mRNA expression was performed on 64
      paired tumor and normal tissues by quantitative real-time RT-PCR. RESULTS:
      Survivin expression in tumors (median 3.68, min. 0.19, max. 28.63) was
      significantly higher (p < 0.04) than in corresponding normal tissues (median
      1.68, min. 0.03, max. 155.59). Survivin mRNA was up-regulated in tumors of 42
      patients (66%). However, survivin overexpression did not correlate with survival
      of lung cancer patients. There was no significant association of survivin mRNA
      levels with histological type (p = 0.29), pT (p = 0.41) and pN categories (p =
      0.57), grading of the primary tumor (p = 0.45), or histopathological stage (p =
      0.87). CONCLUSION: Overexpression of survivin mRNA in NSCLC might be a marker for
      noninvasive tumor detection, but has no prognostic importance.

PMID- 18630508
TI  - TGFbeta regulated gene expression by Smads and Sp1/KLF-like transcription factors
      in cancer.
AB  - Transforming growth factor beta (TGFbeta) controls vital cellular functions
      through its ability to regulate gene expression. TGFbeta binding to its
      transmembrane receptor kinases initiates distinct intracellular signalling
      cascades including the Smad signalling and transcription factors and also Smad
      independent pathways. In normal epithelial cells, TGFbeta stimulation induces a
      cytostatic program which includes the transcriptional repression of the c-Myc
      oncogene and the later induction of the cell cycle inhibitors p15(INK4b) and
      p21(Cip1). During carcinogenesis, however, many tumor cells lose their ability to
      respond to TGFbeta with growth inhibition, and instead, activate genes involved
      in cell proliferation, invasion and metastasis. Strong efforts have been made
      during recent years to characterize Smad-mediated transcriptional processes and
      to identify those TGFbeta-regulated transcription factors that control gene
      expression independent of the Smads. These studies have led to the identification
      of a novel family of TGFbeta-inducible Sp1/KLF-(Kruppel-like factors) like
      transcription factors (KLF10 and KLF11) which play remarkable roles in TGFbeta
      mediated cell growth control and differentiation. In this article, the current
      knowledge on the peculiar roles of Sp1/KLF-like proteins in Smad dependent and 
      independent gene regulation initiated by TGFbeta, are summarized.

PMID- 18630509
TI  - Molecular biology of pancreatic cancer--new aspects and targets.
AB  - Pancreatic ductal adenocarcinoma is a dismal disease with a median survival of
      less than 6 months and an overall 5-year survival rate less than 1%. This bad
      prognosis is due to early lymphatic and hematogenic dissemination. Effective
      therapies for locally advanced or metastatic tumors are very limited and
      curatively resected patients experience relapse in over 80% of cases. Together,
      these findings reflect the aggressive biology of the disease. Here, we describe
      molecular mechanisms leading to unrestrained proliferation, insensitivity to
      growth inhibitory signals, evasion of apoptosis, limitless replicative potential,
      tissue invasion, metastasis and sustained angiogenesis. Potential therapeutic
      targets are highlighted.

PMID- 18630510
TI  - The bisphosphonate, zoledronic acid reduces experimental neuroblastoma growth by
      interfering with tumor angiogenesis.
AB  - BACKGROUND: Zoledronic acid is a new member of the bisphosphonate (BP) class of
      compounds, a family of closely related synthetic molecules originally derived
      from the naturally occurring pyrophosphate. These compounds that are potent
      inhibitors of bone resorption, have been shown to reduce the growth of several
      cancer cell lines in vitro, and can act as inhibitors of angiogenesis. The
      angiogenesis inhibitor TNP-470, a synthetic analogue of the fungal antibiotic
      fumagillin, has been shown to inhibit the growth of multiple tumors in vivo, and
      is currently in Phase II clinical trials for cancer. MATERIALS AND METHODS: The
      effects of daily subcutaneous (s.c.) administration of zoledronic acid (0.1
      mg/kg) were compared with those of TNP-470 (15 mg/kg/day and 30 mg/kg every other
      day, s.c.) in a nude mouse xenograft model for the childhood cancer,
      neuroblastoma (NB). RESULTS: Zoledronic acid reduced the tumor growth by 33%
      whereas TNP-470 was less effective and reduced the tumor growth by 26% and 11%
      for animals treated with 15 mg/kg/day and 30 mg/kg every other day, respectively.
      Analysis of angiogenesis showed a significant reduction of the number of vessels
      per grid and in vessel length in all the treatment groups. CONCLUSION: Zoledronic
      acid shows tumoristatic and angiostatic properties that might be beneficial in
      the treatment of solid tumors such as neuroblastoma.

PMID- 18630511
TI  - Targeting of CDC20 via small interfering RNA causes enhancement of the
      cytotoxicity of chemoradiation.
AB  - BACKGROUND: Cell division cycle 20 homologue (CDC20), which encodes a protein
      that promotes chromosomal separation, is highly expressed in several carcinomas,
      including pancreatic cancer. MATERIALS AND METHODS: To ascertain whether this
      gene could be a potential therapeutic target, the RNA interference technique was
      applied using small interfering RNA (siRNA) to knockdown CDC20 expression.
      RESULTS: The CDC20 siRNA showed more than 90% inhibition of CDC20 expression at
      both the transcriptional and translational levels and the specific knockdown of
      CDC20 expression inhibited the cell growth of human pancreatic carcinoma cells in
      vitro. Suppression of CDC20 induced accumulation of the cells in the G2/M-phase
      of the cell cycle. In addition, the knockdown of CDC20 caused enhancement of the
      cytotoxicity of paclitaxel and increased the effect of gamma-irradiation against
      pancreatic carcinoma cells. CONCLUSION: CDC20 is a promising target for gene
      specific therapy in human pancreatic cancer.

PMID- 18630512
TI  - Flow cytometric phenotype of rhabdomyosarcoma bone marrow metastatic cells and
      its implication in differential diagnosis with neuroblastoma.
AB  - BACKGROUND: The goal of this study was to develop a flow cytometric (FCM) method
      for assessing the presence of metastatic cells in bone marrow (BM) and peripheral
      blood (PB) obtained from rhabdomysarcoma (RMS) patients. Myogenin (Myf4), a
      specific molecular RMS marker, was also investigated in the same samples. Since
      neuroblastoma (NB) metastasizes to the BM, the potential application of cytometry
      in differential diagnosis was explored. PATIENTS AND METHODS: CD45, CD56, CD90
      and CD57 antibodies were used in 7 paired BM and PB samples (from 7 RMS stage IV
      patients at presentation), 23 BM samples (from 13 RMS stage I and II patients at
      presentation), and ten paired BM and PB samples taken at presentation and five BM
      samples taken at recurrence from 13 NB stage 4 patients. RESULTS: All seven BM
      samples from RMS stage IV (but not those from patients with localized disease)
      showed both the CD45- CD56+ phenotype and the Myf4 transcript. Four cases also
      showed CD90 and two CD57 positivity. Neither the CD45- CD56+ phenotype, nor Myf4
      were recorded in the BM and PB samples from patients with localized disease. All
      the NB BM samples (15/15) showed the CD45- CD56+ CD90+ phenotype and 10/15 also
      showed CD57 positivity. Only 3/10 blood samples from the NB patients revealed
      tumor cells. CONCLUSION: CD45, CD56, CD90 and CD57 antibodies can be used in FCM
      for marrow metastasis detection in both, RMS and NB patients.

PMID- 18630513
TI  - Do stem cells participate in cell turnover in duodenal adenomas? A preliminary
      study on Paneth cells.
AB  - BACKGROUND: In the normal duodenum, Paneth cells migrate from the stem cells
      downwards, towards the bottom of the crypts of Lieberkuhn. MATERIALS AND METHODS:
      The spatial position of Paneth cells within the profile of histological sections
      was investigated with hematoxilin and eosin (H&E) in 6 duodenal adenomas; 2 of
      them were also immonostained with lysozyme, an enzyme present in Paneth cells.
      RESULTS: In H&E stain sections, the numbers of mature Paneth cells/high power
      field varied from 2 to 7 (mean 4.5). In the two immunostained adenomas, the
      numbers of lysozyme-expressing cells/high power field were 15 and 42,
      respectively. The lysozyme-stained cells were present at all levels in the
      adenomas, including the luminal epithelial layer. CONCLUSION: In duodenal
      adenomas, not all Paneth cells detected by lysozyme immunostain are apparent in
      H&E-stained sections, suggesting that lysozyme immunostain also detects Paneth
      cells precursors. Since mature Paneth cells and their precursors are positioned
      underneath the stem cells, it is conceivable that the Paneth cells that had
      reached the luminal aspect of the adenomas, were preceded by stem cells. This
      possibility would imply that in duodenal adenomas, the stem cells would be
      subjected to the same laws that orchestrate the turnover of epithelial duodenal
      cells, including Paneth cells and their precursors.

PMID- 18630514
TI  - Messenger RNA expression of translationally controlled tumor protein (TCTP) in
      liver regeneration and cancer.
AB  - OBJECTIVE: Translationally controlled tumor protein (TCTP) was recently reported
      to be involved in tumor reversion. In order to understand TCTP mRNA transcript in
      proliferative tissue and malignant lesions, the mRNA expression of TCTP was
      determined in a rat model of liver regeneration and human liver cancer tissues.
      In addition, the potential role of TCTP on suppression of liver cancer was
      investigated. MATERIALS AND METHODS: Liver regeneration model was established by
      a two-thirds partial hepatectomy (PH) in adult, male Sprague-Dawley rat. TCTP
      mRNA expression was determined by semiquantitative RT-PCR analysis. Antisense
      mRNA of TCTP was transfected into the SMMC-7721 liver cancer cell line.
      Biological assay of proliferation and cell cycle were analysed by MTT and flow
      cytometry, respectively. RESULTS: After PH of rats, the level of TCTP mRNA
      transcript was upregulated slightly in liver tissue at 1 hour followed by a high
      expression from 3 to 12 hours, which then decreased dramatically at 24 hours
      before returning to original level during liver tissue proliferation. TCTP mRNA
      transcript increased significantly in liver cancer tissues when compared to non
      cancerous adjacent tissues as control. The transfection with antisense
      oligodeoxynucleotides of TCTP led to decreased proliferation of SMMC-7721 cells
      resulting in cell cycle arrest and pro-apoptosis. CONCLUSION: The results
      suggested that TCTP mRNA expression might be stage-specific in the proliferation
      of liver tissue but alter abnormally in cancer lesions. TCTP could be used as a
      potential target for suppression of liver tumorigenicity.

PMID- 18630515
TI  - Aberrant methylation of the HACE1 gene is frequently detected in advanced
      colorectal cancer.
AB  - BACKGROUND: It has been recently reported that HACE1, the E3 ubiquitin ligase, is
      epigenetically inactivated in human Wilms' tumors and HACE1 expression was also
      down-regulated in colon carcinomas. MATERIALS AND METHODS: The methylation status
      of the HACE1 gene was examined in primary carcinomas and the corresponding normal
      tissues derived from 32 patients with colorectal cancer using quantitative
      methylation-specific PCR (qMSP) and the correlation between the methylation
      status and the clinicopathological findings was evaluated. RESULTS: Aberrant
      methylation of the HACE1 gene was detected in 9 out of the 32 (28%) primary colon
      carcinomas, suggesting that the aberrant methylation of HACE1 was frequently
      observed in colorectal cancer. The clinicopathological data were then correlated
      with these results. A significant increase was observed in the maximal tumor size
      of the methylated HACE1 tumors (p = 0.0304). Moreover, a trend was shown towards
      preferentially developing lymph node metastasis in the methylated HACE1
      carcinomas (p = 0.0612). CONCLUSION: HACE1 might act as a tumor suppressor in
      colorectal carcinomas and HACE1 methylation might present a malignant potential
      in colorectal cancer.

PMID- 18630516
TI  - Suberoylanilide hydroxamic acid (SAHA) induces apoptosis or autophagy-associated
      cell death in chondrosarcoma cell lines.
AB  - BACKGROUND: Since chondrosarcoma has a high resistance to conventional
      chemotherapy and radiotherapy, surgical resection is currently the only effective
      treatment. Histone deacetylase (HDAC) inhibitor exert anticancer effects, but
      have not been tested in chondrosarcoma. MATERIALS AND METHODS: We investigated
      the phenotypic change in chondrosarcoma cells treated with SAHA by cell viability
      assay, Western blot, flow cytometric analysis and electron microscopy. RESULTS:
      SAHA inhibited the growth of chondrosarcoma cell lines and induced apoptosis in
      SW1353 with a cleaved-PARP expression and sub-G1 fragmentation according to flow
      cytometric analysis. On the other hand, in RCS and OUMS-27, SAHA induced
      autophagy-associated cell death as shown by the detection of autophagosome
      specific protein and specific ultrastructural morphology in the cytoplasm. In
      addition, SAHA significantly inhibited tumor growth in an in vivo xenograft
      model. CONCLUSION: These results suggest that SAHA might be a promising agent for
      performing clinically useful chemotherapy against chondrosarcomas.

PMID- 18630517
TI  - Changes of gene expression of thymidine phosphorylase, thymidylate synthase,
      dihydropyrimidine dehydrogenase after the administration of 5'-deoxy-5
      fluorouridine, paclitaxel and its combination in human gastric cancer xenografts.
AB  - BACKGROUND: Although a variety of combination chemotherapies has been tested in
      gastric carcinoma, the most effective chemotherapeutic regimen and the precise
      mechanisms underlying anticancer agent combination have not yet been sufficiently
      elucidated. MATERIALS AND METHODS: Experimental chemotherapy was performed using
      human gastric carcinoma xenografts, MKN-45 and TMK-1, to examine the anticancer
      effects and gene expressions of the enzymes involved in 5-fluorouracil
      metabolism, thymidine phosphorylase (dThdPase), thymidylate synthase (TS) and
      dihydropyrimidine dehydrogenase (DPD). Nude mice were treated with 5'-deoxy-5
      fluorouridine (5'-dFUrd), or paclitaxel alone or in combination. The in vivo
      antitumor effects on gene expressions of the enzymes were examined using the
      quantitative real-time RT-PCR method. RESULTS: The combined use of 5'-dFUrd and
      paclitaxel showed additive to synergistic antitumor effects on both gastric
      cancer xenografts. There were significant differences of the gene expressions of
      dThdPase, TS, and DPD between the xenografts. The expression of dThdPase mRNA was
      consistently up-regulated by the administration of paclitaxel, while no constant
      direction of TS mRNA and DPD mRNA change was found in the xenografts. CONCLUSION:
      A synergistic antitumor effect of the combined administration of 5'-dFUrd and
      paclitaxel was found in gastric cancer xenografts and up-regulation of dThdPase
      mRNA may be an important underlying mechanism especially in tumors with high gene
      expression of this enzyme.

PMID- 18630518
TI  - Gross thymic extract, Thymax, induces apoptosis in human breast cancer cells in
      vitro through the mitochondrial pathway.
AB  - Previous studies have shown that thymic extracts possess antitumor and
      antimetastatic properties, but the mechanisms are not completely understood.
      Therefore, in this study the ability of the gross thymic extract Thymax to induce
      apoptosis in human breast cancer cell line (MCF-7) cells in vitro was evaluated.
      Tumor cells were cultured with different concentrations of Thymax for 24 h and
      the apoptotic response was assessed by propidium iodide and TUNEL assays.
      Activation of caspases and changes in mitochondrial membrane potential (MMP) were
      monitored by flow cytometry and the expression of Bcl-2 and Bax was determined by
      Western blot analysis. Thymax induced apoptosis in monolayer MCF-7 cells in a
      dose-dependent manner; at concentrations of 2.5, 5 and 10% (v/v) it caused 9%,
      10% and 25% apoptosis, respectively, as compared to 6% for control cancer cells
      without treatment. The induction of apoptosis by Thymax was associated with
      activation of caspases 8 and 9, and the addition of a pan caspase inhibitor
      partially inhibited Thymax-induced apoptosis by 20%. In addition, the MMP was
      decreased significantly at Thymax concentrations of 5%-20%, which was associated
      with a decrease in the protein expression of Bcl-2 and an increase in Bax. These
      results suggest that Thymax exerts its effects via the mitochondrial pathway of
      apoptosis and may represent a new class of adjuvants for the treatment of breast
      cancer.

PMID- 18630519
TI  - Establishment of transplantable murine osteosarcoma cell line with endochondral
      ossification.
AB  - Osteosarcoma is defined as a malignant mesenchymal tumor in which tumor cells
      produce bone matrix. Osteosarcoma cell line (Nishi-Hirosaki osteosarcoma, NHOS)
      from a spontaneous soft tissue tumor in an athymic mouse was established. The
      cultured NHOS cells formed a monolayer consisting of spindle to polygonal cells
      without extracellular matrix formation or mineralization. In contrast, the
      transplanted NHOS tumor in immunodeficient mice consisted of short spindle and
      pleomorphic cells, associated with networks of calcified bone and osteoid
      matrices, as well as small foci of chondroid matrix. Pulmonary metastasis was
      detected in 22 (42.3%) out of the 52 tumor-bearing mice when NHOS cells were
      transplanted into the murine flanks. Pulmonary metastasis was detected in all
      mice (6/6) at post-injection days 21-49 when the cells were injected into the
      murine tail veins. The NHOS transplantable osteosarcoma cell line with ossifying
      ability would be useful to clarify the mechanisms of aggressive metastatic
      potential, as well as for studying the ossification process involved in cell-to
      matrix interactions.

PMID- 18630520
TI  - Vinorelbine is effective for the malignant pleural effusion associated with lung
      cancer in mice.
AB  - Malignant pleural effusion (MPE) is associated with advanced-stage lung cancer.
      Vinorelbine (VNR) is a semisynthetic vinca alkaloid with strong antitumor
      activity in non-small cell lung cancer (NSCLC). The purpose of this study was to
      evaluate the effect of VNR on the production of MPE associated with lung cancer.
      To investigate the therapeutic efficacy of VNR in the production of MPE in mice,
      cells of the murine lung cancer cell line, 3LL, were injected into the pleural
      space of mice, and VNR was administered once intravenously. Treatment with VNR
      almost completely inhibited tumor growth and MPE production. In addition,
      immunohistochemical staining revealed that neovascularization and vascular
      endothelial growth factor (VEGF) expression were markedly decreased in VNR
      treated tumors compared with those of the control tumors. Treatment of 3LL cells
      with high concentrations of VNR (5 or 10 nM) significantly inhibited cell
      proliferation in vitro. Interestingly, low concentrations of VNR (1 or 2.5 nM)
      did not affect 3LL cell proliferation, but markedly reduced VEGF expression in
      these cells. These results suggest that VNR may be effective for the treatment of
      MPE associated with lung cancer not only by its cytotoxic effect but also through
      down-regulation of VEGF expression in lung cancer cells.

PMID- 18630521
TI  - Apoptosis regulation and spontaneous apoptosis index of testicular germ cell
      tumors are associated with differentiation and resistance to systemic treatment.
AB  - BACKGROUND: Cisplatin-based chemotherapy can cure more than 80% of metastatic
      germ cell testicular tumors (GCT). Germ cells are particularly susceptible to
      apoptosis and it is reasonable to presume that GCTs are curable because of an
      intact and effective apoptotic pathway. PATIENTS AND METHODS: The expression of
      p53 and p21 was investigated in conjunction with the spontaneous apoptotic index
      in 20 refractory and 50 chemosensitive GCTs, with a complete follow-up. To detect
      a differentiation-dependent alteration in the apoptotic pathway, all of the
      histological tumor types were examined separately. RESULTS: Embryonal carcinoma
      components showed significantly higher p53 expression compared to other
      histological subtypes of GCTs. p21 was barely detectable in the majority of
      tumors. Seminomatous components showed no p21 expression. Mature teratomas and
      syncytiotrophoblasts showed significantly higher p21 expression than other tumor
      subtypes. Embryonal carcinomas showed significantly higher apoptotic indices than
      other non-seminomatous components. On the other hand, choriocarcinomas and mature
      teratomas showed the lowest spontaneous apoptotic potential. The apoptotic index
      correlated with the fraction of p53-positive cells, but not with the p21
      expression rate. The refractory group showed significantly lower p53 expression,
      higher p21 expression and a higher apoptosis index than the sensitive group.
      CONCLUSION: Our results suggest that the p53 and p21 expression levels and the
      apoptosis index seem to be important factors in the issue of the chemosensitivity
      of GCTs. The protein expression pattern reflects a differentiation-dependent
      preference for G1/S-phase arrest in terminally differentiated
      syncytiotrophoblasts and mature teratoma cells, while p53 mediated apoptosis
      induction is meaning to less differentiated tumor types.

PMID- 18630522
TI  - Development of 36 clones producing human monoclonal antibodies specific to cancer
      cells and their ability to inhibit cancer cell growth.
AB  - The development of a specific antibody for cancer therapy could enable a potent
      strategy for overcoming cancer. As ideal immunotherapy, a human monoclonal
      antibody (HuMoAb) might have a useful antitumor effect without any lethal
      toxicities. Thirty-six unique clones producing HuMoAbs were successfully
      developed using tumor infiltrating lymphocytes collected from 28 patients with
      several malignant solid tumors. The 36 tumor-specific immunoglobins were found
      among 9,450 clones after 43 fusions by the conventional hybridoma method. Among
      these 36 HuMoAbs, 9 had a remarkable tumor-specific reaction and no reaction with
      normal tissues, as determined with quantum dots-streptavidin and a fluorescence
      microscope. The inhibition of cell proliferation by the HuMoAbs was evaluated
      with the MTT assay. Over 40% cell growth inhibition was confirmed with 4 of the
      36 HuMoAbs. Two of the antibodies had highly-specific reactivity to carcinomatous
      lesions with strong growth inhibition and up to 94.3% inhibition of the control
      growth. In conclusion, 36 clones with HuMoAbs that have specific reactions with
      cancer cells were successfully established. These HuMoAbs might be utilized as
      either anticancer or drug delivery agents.

PMID- 18630523
TI  - Hypoxia inducible factor-alpha expression correlates with vascular endothelial
      growth factor-C expression and lymphangiogenesis/angiogenesis in oral squamous
      cell carcinoma.
AB  - BACKGROUND: The number of blood vessels correlates with metastasis in solid
      tumors, including oral squamous cell carcinoma (OSCC). Hypoxia inducible factor
      1alpha (HIF-1alpha) could play a role in tumor lymphangiogenesis by regulating
      the lymphatic expression of vascular endothelial growth factor-C (VEGF-C). HIF
      1alpha protein expression, VEGF-C protein expression, lymphatic vessel density
      (LVD) and blood vessel density (BVD) in OSCC were investigated. MATERIALS AND
      METHODS: HIF-1alpha and VEGF-C protein expression were investigated by means of
      immunohistochemistry in samples from 65 cases of OSCC. The density of the
      lymphatic microvessels and blood microvessels immunohistochemically stained by
      LYVE-1 and CD34 antibody, respectively, was calculated. The association between
      the HIF-1alpha expression and the clinicopathological parameters was evaluated.
      RESULTS: HIF-1alpha overexpression occurred in 43 out of the 65 tumor samples
      (66.2%), while VEGF-C overexpression was observed in 34 out of the 65 tumor
      samples (52.3%). Higher LVD was found in both high HIF-1alpha and high VEGF-C
      expression cases. HIF-1alpha overexpression was significantly correlated with
      VEGF-C overexpression (p = .018, Chi-square test), higher LVD (p < 0.001, Mann
      Whitney U-test), and regional lymph nodal involvement (p = 0.004, Chi-square
      test) as well as UICC TMN classification (p = 0.043, Chi-square test),
      respectively. In addition, higher BVD existed in the high HIF-1alpha and VEGF-C
      expression groups (p < 0.001, Mann-Whitney U-test). CONCLUSION: HIF-1alpha might
      play a crucial role in regional lymph node metastasis as a regulator of
      lymphangiogenesis and angiogenesis in OSCC with a possible novel pathway
      involving VEGF-C. Therefore, HIF-1alpha might be a particularly promising target
      for controlling regional lymph node metastases by a combination of antiangiogenic
      and anti-lymphangiogenic effects in OSCC.

PMID- 18630524
TI  - Identification and characterization of two splicing variants of human Noxa.
AB  - Noxa is a pro-apoptotic Bcl-2 homology 3 (BH3)-only containing protein. Here we
      report the identification of two splicing variants of the human Noxa gene, which
      consists of three exons and two introns. Alternative splicing of exon 2 yields
      three transcripts. Transcript-1 joins exons 1 and 3 to encode Noxa of 54 amino
      acids. Transcript-2, consisting of exon-1, partially spliced exon-2, and exon-3,
      encodes NSV-1 (Noxa splicing variant-1) of 136 amino acids, whereas transcript-3,
      containing all three exons, encodes NSV-2 of 70 amino acids, which is 100%
      identical to the first 70 amino acids of NSV-1. All three transcripts, controlled
      by the same promoter with two p53 consensus-binding sites, were inducible by p53.
      Although NSV-1 and NSV-2 mRNA were readily detectable by RT-PCR in multiple human
      cancer cell lines, no endogenous variant proteins were detected under
      physiological or stressed conditions. Even under forced expression, both variants
      were barely detectable without proteasome inhibitor, MG132. The protein half-life
      of the two variants is approximately 40 to 60 mins with MG132, suggesting they
      are rapidly degraded via proteasome-dependent and independent pathways. Unlike
      Noxa, BH3-less variants failed to potentiate apoptosis induced by etoposide.
      Thus, Noxa variants are unlikely to play a role in apoptosis regulation.

PMID- 18630525
TI  - Angiotensinogen polymorphism is associated with risk for malignancy but not for
      oral cancer.
AB  - BACKGROUND: In light of the recently found contribution of angiogenic and
      inflammation-related factors to malignancies, this study investigated the
      possible association of the angiotensinogen gene (AGT) with increased risk of
      oral cancer. MATERIALS AND METHODS: The M235T polymorphism, which influences AGT
      gene expression, was evaluated by restriction fragment length polymorphism
      analysis in the DNA samples of 163 German and Greek patients with oral squamous
      cell carcinoma (OSCC) and 124 healthy controls of equivalent gender, ethnicity
      and age. RESULTS: No significant difference of the mutant (235T) allele, which
      results in higher AGT gene expression, was observed in the whole patient group in
      comparison with the normal controls. Similarly, compared to the controls no
      significant difference of either allele or carrier frequency was detected in
      almost every subgroup of patients. Only in the subgroup of patients with a
      positive family history of cancer was a significant increase of mutant T allele
      and carrier frequencies observed, compared to the controls (50% vs. 36.7% and
      79.3% vs. 61.3%, respectively, p < 0.05 in both cases). In this particular
      subgroup of patients the odds ratio for OSCC of TT homozygotes was 3.57 (CI 95%
      1.2-10.62), while for the MT heterozygotes it was 2.41 (CI 95% 1.06-5.49).
      CONCLUSION: This study did not reveal an association of the AGT M235T
      polymorphism with oral oncogenesis, but certainly suggested a possible
      association of this specific polymorphism with other types of cancer. The present
      findings support a previous suggestion that the pathway of oral oncogenesis is
      probably based on angiotensin-converting enzyme and bradykinin interaction and
      not on AGT and angiotensin peptides.

PMID- 18630526
TI  - Caffeine dose-dependently potentiates the antitumor effect of cisplatin on
      osteosarcomas.
AB  - BACKGROUND: Caffeine-assisted chemotherapy has been used in the treatment of
      osteosarcomas. However, there is little in vivo evidence for this treatment, and
      thus we sought to verify the dose and effect of caffeine in combination with
      cisplatin in osteosarcoma-bearing rats. MATERIALS AND METHODS: Seven-week-old
      male Fischer rats were transplanted with chemical carcinogen-induced
      osteosarcoma, selected lung metastatic lesions tumor block. The osteosarcoma
      bearing rats were treated with saline, caffeine, cisplatin or cisplatin and
      caffeine. RESULTS: The most growth inhibition was observed in the co
      administration group. When three different dosing schedules of caffeine were
      given, the extent of tumor inhibition was closely correlated with the average
      plasma concentration of caffeine. The cisplatin concentration in the tumor was
      significantly increased when caffeine was co-administered. CONCLUSION: This study
      confirms that a high concentration of caffeine (about 0.4 mM) is effective in
      enhancing the antitumor effects of cisplatin.

PMID- 18630527
TI  - Association of XRCC4 codon 247 polymorphism with oral cancer susceptibility in
      Taiwan.
AB  - BACKGROUND: The DNA repair gene XRCC4, an important caretaker of overall genome
      stability, is thought to play a major role in the development of human
      carcinogenesis. However, the association of the polymorphic variants of XRCC4
      with oral cancer susceptibility has never been reported. MATERIALS AND METHODS:
      In this hospital-based case-control study, the association of XRCC4 codon 247
      (rs3734091), G-1394T (rs6869366), intron 7 (rs28360317) and intron 7 (rs1805377)
      polymorphisms with oral cancer risk in a Central Taiwanese population was
      investigated. In total, 318 patients with oral cancer and 318 age- and gender
      matched healthy controls recruited from the China Medical Hospital in Central
      Taiwan were genotyped. RESULTS: A significantly different distribution was found
      in the frequency of the XRCC4 codon 247 genotype, but not the XRCC4 G-1394T or
      intron 7 genotypes, between the oral cancer and control groups. A/C
      heterozygosity at XRCC4 codon 247 conferred a significant (2.04-fold) increased
      risk of oral cancer. As for XRCC4 G-1394T and intron 7 polymorphisms, there was
      no difference in distribution between the oral cancer and control groups. Gene
      environment interactions with smoking, but not with betel quid chewing or alcohol
      consumption, were significant for XRCC4 codon 247 polymorphism. The XRCC4 codon
      247 A/C genotype in association with smoking conferred an increased risk of 3.44
      (95% confidence interval = 1.24-9.60) for oral cancer. CONCLUSION: Our results
      provide the first evidence that the heterozygous A allele of the XRCC4 codon 247
      may be associated with the development of oral cancer and may be a novel useful
      marker for primary prevention and anticancer intervention.

PMID- 18630528
TI  - Enhancement of sodium butyrate-induced cell death by hyperthermia in HCT 116
      human colorectal cancer cells.
AB  - AIM: The possible enhancing effect of the combined use of sodium butyrate (SB)
      and hyperthermia to kill HCT 116 cells was evaluated. MATERIALS AND METHODS: HCT
      116 cells were subjected to SB (1 mM) treatment followed by hyperthermia (44
      degrees C 60 min) and the effects on cell death, cell proliferation and the cell
      cycle were examined. Apoptosis-indicating protein expressions and intracellular
      superoxide formation were also analysed. RESULTS: A marked reduction in the
      growth rate of the combined-treatment group was observed compared to those of the
      single-treatment groups. This involved the increased expression of p53 and p21,
      the alteration of the balance of anti- and proapoptotic Bcl-2 family proteins and
      enhanced superoxide formation. However, the death receptor pathway played no
      role. CONCLUSION: Hyperthermia synergistically promoted cell death induced by SB.
      Thus, the combined treatment led to mutual potentiation of the killing effects of
      each agent.

PMID- 18630529
TI  - The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer
      cells through mitochondria- and caspase-3-dependent pathway.
AB  - Baicalein was investigated for tumor cell-specific cytotoxicity, apoptosis
      inducing activity and signal pathway against the MDA-MB-231 human breast cancer
      cell line. After the MDA-MB-231 cells had been treated with baicalein, trypan
      blue exclusion, propidium iodide (PI) assay and 4',6-diamidino-2-phenylindole
      (DAPI) were used to stain the dead cells and detect apoptosis, respectively. The
      effects of baicalein on the levels of reactive oxygen species (ROS), Ca2+ and
      mitochondrial membrane potential (deltapsim) on MDA-MB-231 cells were examined by
      flow cytometric assays. The ROS caused endoplasmic reticulum (ER) stress,
      confirmed by the increase of GADD153 and GRP78 in the examined cells. GADD153 and
      GRP78 increases were also confirmed by confocal laser microscopy examination and
      indicated that both proteins translocated to the nucleus. The effects of
      baicalein on the expression of apoptotic-regulated genes, such as Bcl-2 family
      and caspase, were detected by Western blotting. To further investigate the
      apoptotic pathway and the role of Ca2+ induced by baicalein, a caspase-3
      inhibitor and Ca2+ chelator were used to block caspase-3 activity and Ca2+ in MDA
      MB-231 cells. Baicalein induced apoptosis in a time-dependent effect through the
      inhibition of Bcl-2 expression, increased the levels of Bax, reduced the level of
      deltapsim, and promoted the cytochrome c release and caspase-3 activation. MDA-MB
      231 cells were pretreated with BAPTA which reduced the levels of Ca2+, deltapsim
      and apoptosis. In conclusion, baicalein induced apoptosis via Ca2+ production,
      mitochondria-dependent and caspase-3 activation in MDA-MB-231 cells.

PMID- 18630530
TI  - Induction of apoptosis by epigallocatechin gallate and autophagy inhibitors in a
      mouse macrophage-like cell line.
AB  - We have previously reported that lignin carbohydrate complex and E. coli
      lipopolysaccharide (LPS), but not their precursors or (-)-epigallocatechin-3
      gallate (EGCG), enhanced the nitric oxide (NO), citrulline and asparagines
      production by the mouse-macrophage-like cell line Raw264.7. Here the EGCG
      inhibition of NO production by LPS-stimulated Raw264.7 cells is reported. EGCG
      induced apoptotic cell death characterized by internucleosomal DNA fragmentation,
      whereas it inhibited the formation of secondary lysosomes and autophagosomes
      detected as granular dot-like distribution of acridine orange and microtubule
      associated protein light chain 3 fused with green fluorescent protein (LC3-GFP).
      Autophagy inhibitors such as 3-methyladenine and bafilomycin A1 induced apoptotic
      cell death in the Raw264.7 cells. The inhibition of macrophage NO production by
      EGCG may be due to the apoptosis induction coupled with autophagy inhibition.

PMID- 18630531
TI  - Expression of VEGFR-1 (Flt-1) in breast cancer is associated with VEGF expression
      and with node-negative tumour stage.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) promotes breast cancer
      progression by inducing angiogenesis via VEGF receptors on endothelial cells but
      also signals directly through receptors such as VEGFR-1 (Flt-1) expressed on
      tumour cells. The impact of autocrine signalling loops on treatment with VEGF
      inhibitors is still unclear. MATERIALS AND METHODS: Six breast cancer cell lines
      were tested for expression of VEGFR-1 by RT-PCR and Western blot. To assess
      clinical significance, 93 breast cancer lesions were evaluated for expression of
      VEGF and VEGFR-1 by immunohistochemistry. RESULTS: VEGFR-1 mRNA was found in all
      6 cell lines, while protein expression was found in 5 cell lines. VEGF was
      expressed in 60% and VEGFR-1 in 39% of breast cancer specimens. VEGFR-1
      expression was associated with VEGF expression and with node-negative tumour
      stage. CONCLUSION: Our data suggest that analysis of VEGF/VEGFR-1 expression
      might be relevant in identifying patients with different response rates upon
      treatment with antiangiogenic agents.

PMID- 18630532
TI  - [Moxibustion on heat-sensitive acupoints for treatment of myofascial pain
      syndrome: a multi-central randomized controlled trial].
AB  - OBJECTIVE: To observe the clinical therapeutic effect of moxibustion on heat
      sensitive acupoints on myofascial pain syndrome (MPS). METHODS: Three-centre,
      single blind, randomized controlled trial method was adopted. One hundred and
      seven cases were randomly divided into an observation group (n = 57), and a
      control group (n = 50). The observation group were treated by moxibustion on the
      heat-sensitive acupoints and the control group by acupuncture, cupping and TDP.
      The therapeutic effects were assessed according to changes of the score of the
      short-form of McGill pain questionnaire composing of pain rating index (PRI),
      visual analogue scale (VAS) and present pain intensity (PPI) before and after
      treatment. RESULTS: The cured rate of 86.0% in the observation group was better
      than 24.0% in the control group. After treatment, the score of PRI, VAS, PPI
      indexes significantly improved in the observation group (P < 0.001), and were
      significantly better than those in the control group (P < 0.001). CONCLUSION:
      Moxibustion on the heat-sensitive acupoints has a high therapeutic effect on MPS.

PMID- 18630533
TI  - [Observation on therapeutic effect of acupuncture combined with western medicine
      on paralytic strabismus].
AB  - OBJECTIVE: To find out a better therapy for paralytic strabismus. METHODS: Ninety
      cases were randomly divided into an acupuncture-medicine group, an acupuncture
      group, a western medicine group, 30 cases in each group. The acupuncture-medicine
      group were treated with acupuncture at Shuigou (GV 26), Fengchi (GB 20), Yifeng
      (TE 17), Yiming (EX-HN 14), Taiyang (EX-HN 5), Jingming (BL 1), Cuanzhu (BL 2),
      etc. intramuscular injection of Vit B1 and Vit B12, and oral administration of
      ATP; the acupuncture group were treated with simple acupuncture, and the western
      medicine group were treated with simple western medicine. Their therapeutic
      effects were compared. RESULTS: The cured rate of 66.7% in the acupuncture
      medicine group was significantly higher than 26.7% in the acupuncture group and
      26.7% in the western medicine group (both P < 0.01). CONCLUSION: Acupuncture
      combined with western medicine has obvious therapeutic effect, which is better
      than that of simple acupuncture or simple western medicine.

PMID- 18630534
TI  - [Observation on therapeutic effect of acupoint sticking therapy on simple
      obesity].
AB  - OBJECTIVE: To probe into effectiveness and safety of acupoint sticking therapy
      for simple obesity. METHODS: One hundred and eight cases were randomly divided
      into an acupoint sticking group (n = 58) and an acupuncture group (n = 50). The
      acupoint sticking group were treated with TCM plaster sticking at Zhongwan (CV
      12), Guanyuan (CV 4), Qihai (CV 6), etc. The acupuncture group were treated with
      simple acupuncture at Zhongji (CV 3), Guanyuan (CV 4), Qihai (CV 6), etc. Their
      therapeutic effects were observed after 3 therapeutic courses. RESULTS: The total
      effective rate was 84.5% in the acupoint sticking group, 86.0% in the acupuncture
      group with no significant difference between the two groups (P > 0.05); after
      treatment, the body weight, body mass index, waist circumference, hip
      circumference decreased and the cumulative score of clinical symptoms decreased
      in the two groups with no significant difference between the two groups, but the
      waist-hip ratio did not significantly change. CONCLUSION: TCM acupoint sticking
      therapy has a definite therapeutic effect on simple obesity.

PMID- 18630535
TI  - [Observation on therapeutic effect of multiple cupping at back-shu points on
      chronic fatigue syndrome].
AB  - OBJECTIVE: To observe therapeutic effect of multiple cupping at back-shu points
      of zang-and fu-organs on chronic fatigue syndrome. METHODS: One hundred and
      ninety-one cases were randomly divided into 2 groups. The multiple cupping group
      (n = 142) were treated with multiple cupping along both sides of the spinal cord,
      and the acupuncture group (n = 49) were treated with acupuncture at acupoints
      selected according to TCM syndrome differentiation. Their therapeutic effects
      were assessed by clinical symptoms and Fatigue Assessment Indexes (FAI). RESULTS:
      The total effective rate was 97.9% in the multiple cupping group and 79.6% in the
      acupuncture group with a very significant difference between the two groups (P <
      0.01), and after treatment, there was a very significant difference between the
      two groups in FAI score (P < 0.01). CONCLUSION: Multiple cupping at back-shu
      points of zang-and fu-organs is an effective method for chronic fatigue syndrome.

PMID- 18630536
TI  - [Observation on therapeutic effect of auricular acupuncture combined with body
      acupuncture for treatment of cardiac neurosis].
AB  - OBJECTIVE: To find an effective therapy for cardiac neurosis. METHODS: Seventy
      two cases were randomly divided into an acupuncture group and a medication group,
      36 cases in each group. The acupuncture group were treated with auricular
      acupuncture combined with body acupuncture, with auricular points Shenmen,
      Jiaogan (sympathesis), Xin (heart), etc. and body points Xinshu (BL 15), Shenmen
      (HT 7), Neiguan (PC 6), etc. selected; the medication group were treated with
      oral administration of Betaloc and Oryzanol. Their therapeutic effects were
      compared after treatment for 2 months. RESULTS: The cured rate was 77.8% in the
      acupuncture group and 52.8% in the medication group with very significant
      differences (P < 0.01), the former being better than the latter. CONCLUSION:
      Auricular acupuncture combined with body acupuncture is the best method for
      treatment of cardiac neurosis.

PMID- 18630537
TI  - [Effect of acupuncture combined with massage of sole on sleeping quality of the
      patient with insomnia].
AB  - OBJECTIVE: To assess effect of acupuncture combined with massage of sole on
      sleeping quality of the patient with insomnia. METHODS: Fifty-eight cases of
      insomnia were randomly divided into an observation group (n = 32) and a control
      group (n = 26). The observation group were treated with oral administration of
      Alprazolam, massage of sole, and acupuncture at Zhongwan (CV 12), Guanyuan (CV
      4), Qihai (CV 6), etc. on the abdomen as main points; the control group were
      treated with Alprazolam. Clinical therapeutic effects, and scores for Pittsburgh
      Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS) and Self-rating
      Depression Scale (SDS) were assessed before and after treatment in the two
      groups. RESULTS: The effective rate was 93.75 in the observation group and 88.46%
      in the control group with no significant difference between the two groups; after
      treatment, there were significant or very significant differences in scores for
      various factors in the PSQI, SAS and SDS (P < 0.01, P < 0.05). CONCLUSION:
      Abdominal acupuncture as main combined with massage of sole can obviously improve
      sleeping quality of the patient with insomnia.

PMID- 18630538
TI  - [Transient therapeutic effect and safety of superficial needling therapy for
      treatment of periarthritis of shoulder].
AB  - OBJECTIVE: To scientifically assess effectiveness and safety of mono-use fu
      needle. METHODS: Sixty cases of periarthritis of shoulder were randomly divided
      into a fu-needle group and a routine acupuncture group. The fu-needle group were
      treated with fu-needle, and the routine acupuncture group were treated with a
      needle of 0.38 mm in diameter and 40 mm in length. The articular mobility of the
      most limited direction, soft tissue pain self-rating score and self-rating score
      of shoulder tenderness before and after treatment, stabbing times and degree at
      inserting the needle, scattering and during retention of the needle, and bleeding
      at withdrawing the needle were compared in the two groups. RESULTS: The fu-needle
      group was better than the routine acupuncture group in improvement of mobility
      related pain, tenderness, and the articular mobility of the most limited
      direction, indicating that the transient effect in the fu-needle group was better
      than the routine acupuncture group, and the stabbing times and degree at
      insertion of the needle were less than the routine acupuncture group. And there
      was no significant difference between the two groups in stabbing times and degree
      at scattering and retaining the needle and bleeding times in withdrawing the
      needle. CONCLUSION: The superficial needling therapy with mono-use fu-needle is
      more effective and more safe than the routine acupuncture for treatment of
      periarthritis of shoulder.

PMID- 18630539
TI  - [Clinical study on the indications of 33 acupoints].
AB  - Multi-central randomized controlled method was used to scientifically verify
      indications of 33 acupoints and provide definite clinical basis for the
      indications of single acupoint. Of the 52 studies, 40 studies showed that the
      therapeutic effect in acupuncture observation groups were better than the control
      group; 11 studies showed similar therapeutic effect of the two groups, and 1
      study showed the acupuncture observation group was worse than the control group.
      Therefore, results indicate that in a certain observation cycle, acupuncture at
      single acupoint have different effects on diseases.

PMID- 18630540
TI  - [Manipulation methods of slow-rapid reinforcing-reducing method].
AB  - After consulting literature, following the original meaning of the paper about
      slow-rapid reinforcing-reducing method in Huangdi's Internal Classic, in
      combination with explanation of later ages, and comprehension and clinical
      experience of the authors, it is put forward that the slow-rapid reinforcing
      reducing method in Huangdi's Internal Classic is not single manipulation method,
      but it is a guiding principle for reinforcing-reducing manipulation, it includes
      many manipulation methods and they were listed, and all of the reinforcing
      reducing methods of later ages are developed from these. In the teaching material
      Acupuncture and Moxibustion Sciences they are included in single reinforcing
      reducing method, reducing extension and intension of this definition. The
      relative description in the teaching material only is slow-rapid reinforcing
      reducing method of narrow sense, but the manipulations can be divided into qi
      carrying manipulating needle type and three-one pushing-pulling type.

PMID- 18630541
TI  - [Clinical observation on Jiquan (HT 1) for treatment of cervical spondylosis of
      nerve root type].
AB  - OBJECTIVE: To observe acupuncture at Jiquan (HT 1) with different manipulations
      for improvement of abnormal sensation of the upper limb induced by cervical
      spondylosis of nerve root type. METHODS: One hundred and seven cases were
      randomly divided into 3 groups. The lifting-thrusting group (n = 37) were treated
      with acupuncture at Jiquan (HT 1) with lifting-thrusting manipulation, the
      twirling group (n = 36) with acupuncture at Jiquan (HT 1) with twirling
      manipulation and the routine needling group (n = 34) with acupuncture at C4 - T1
      Jiaji (EX-B 2), Quchi (LI 11). RESULTS: The total effective rate of 91.9% in the
      lifting-thrusting group was significantly better than 58.3% in the twirling group
      (P < 0.005) and 76.5% in the routine needling group (P < 0.05), and the
      therapeutic effect of the twirling group was similar to that in the routine
      needling group CP > 0.05). CONCLUSION: Acupuncture at Jiquan (HT 1) with lifting
      thrusting manipulation can obviously improve abnormal sensation of the upper limb
      induced by cervical spondylosis of nerve root type.

PMID- 18630542
TI  - [Study on the mechanism of acupuncture at Daling (PC 7) for mental diseases by
      fMRI].
AB  - OBJECTIVE: To probe into the central nervous mechanism of acupuncture at Daling
      (PC 7) treating mental diseases by fMRI. METHODS: Eight healthy volunteers were
      enrolled in the study. Acupuncture stimulation was given at Daling (PC 7) in each
      subject with a stimulating pattern, "rest-stimulation-rest-stimulation-rest". The
      fMRI data were analyzed with SPM 2 software package. RESULTS: The activating
      areas of acupuncture at Daling (PC 7) were mainly on Brodmann 46/47/44/9 areas of
      inferior frontal gyrus, Brodmann 6 area of middle frontal gyrus, Brodmann 22 area
      of superior temporal gyrus and Brodmann 40 area of postcentral gyrus and inferior
      parietal lobule. CONCLUSION: Pathogenetic factors of mental diseases are very
      complicated, damange or hypofunction or inadequate activation of frontal lobe and
      temporal lobe are closely related with mental diseases. Therefore, activating the
      frontal and temporal lobe possibly is one of the mechanisms of acupuncture at
      Daling (PC 7) treating mental diseases.

PMID- 18630543
TI  - [Effects of electroacupuncture at shu-points of the five zang-organs on
      electrophysiologic function of sciatic nerve in the rabbit of Guillain-Barre
      syndrome].
AB  - OBJECTIVE: To probe into the mechanism of electroacupuncture at shu-points of the
      five zang-organs for treatment of Guillain-Barre syndrome (GBS). METHODS: Eighty
      healthy giant-ear white rabbits were randomly divided into 4 groups, a blank
      group, a model group, an electroacupuncture (EA) group and an immunoglobulin
      group, 20 rabbits in each group. The internationally recognized P 2 immune rabbit
      model was used in the study. The EA group were treated with EA at shu-points of
      the five zang-organs and the immunoglobulin group with intravenous injection of
      immunoglobulin 80 mg/kg/day. The sciatic nerve movement conduction velocity (MCV)
      and F wave incidence rate were investigated respectively at the 7th and 14th days
      of treatment in the rabbits of GBS. RESULTS: The sciatic nerve MCV significantly
      reduced in the model group, and it significantly increased (P < 0.01) and F wave
      abnormal cases was significantly reduced (P < 0.05) after treatment for 14 days
      in the EA group as compared with those in the model group. CONCLUSION: EA at shu
      points of the five zang-organs can increase the sciatic nerve MCV and decrease
      the abnormal F wave incidence rate of the sciatic nerve in the rabbit of GBS.

PMID- 18630544
TI  - [Critical appraisal of randomized clinical trials in Chinese Acupuncture and
      Moxibustion from 2000 to 2006].
AB  - To assess the quality of randomized controlled trials (RCTs) published in Chinese
      Acupuncture and Moxibustion. Manually retrieve RCT papers published in Chinese
      Acupuncture and Moxibustion from 2000 to 2006 and use "the extraction form of
      acupuncture and moxibustion randomized clinical trial report data" to evaluate
      the quality of RCTs. Six hundred and eighty-six RCTs were enrolled. The
      methodological quality was lower than the international standard and only one RCT
      paper described the trial technological process. And there were a less reports
      about influencing RCT quality, such as acupuncturist's qualification and
      education background (3.06%), adverse reaction (4.23%), blind method (5.98%) and
      follow-up (14.43%). RCTs on acupuncture and moxibustion published in Chinese
      Acupuncture and Moxibustion need to be improved in trial design, conduction and
      report.

PMID- 18630545
TI  - [Professor HUANG Xuan-Wei's clinical experience in acupuncture and moxibustion].
AB  - Professor HUANG's clinical acupuncture and moxibustion characters are introduced
      from selection of acupoints, needles used, needling methods, etc. Based on the
      differentiation of symptoms and signs, he is good at using pair-points and
      syndrome differentiation, point-through-point acupuncture and combined many
      methods, and pays attention to adjusting mental activity, promoting flow of qi,
      treating both body and mental treatment. He also uses other therapies besides
      acupuncture and adopts good advance from others, so as to greatly increase
      clinical therapeutic effects.

PMID- 18630546
TI  - [Professor XU Rui-Zheng's experience in clinical diagnosis and treatment of
      auricular acupuncture].
AB  - Professor XU Rui-Zheng's experience in clinical diagnosis and treatment of
      auricular acupuncture are introduced. He is good at using auricular acupuncture
      to treat various diseases and symptoms, and he has rich experience in treatment
      of difficult and complicated cases, reflecting both syndrome differentiation
      treatment and an organic conception of the human body in treatment, with
      obviously clinical effect. He sums up clinical experience of many years,
      attaining the experience of ten wards, i.e. observation, touching, searching,
      detection, questioning, treatment program, pressing, treatment, regulation,
      advance.

PMID- 18630547
TI  - [Application of acupuncture compound anesthesia in transvaginal ultrasound-guided
      oocyte retrieval].
AB  - OBJECTIVE: To observe analgesic effect and safety of acupuncture compound
      anesthesia in transvaginal ultrasound-guided oocyte retrieval. METHODS: Three
      hundred and sixteen cases undergoing in vitro fertilization and embryo transfer
      (IVF-ET) were randomly allocated to an acupuncture compound anesthesia group (n =
      146) and a simple Pethidine group (n = 170). They received respectively
      electroacupuncture combined with intramuscular injection of Pethidine and simple
      intramuscular injection of Pethidine 30 min before oocyte retrieval. RESULTS: The
      acupuncture compound anesthesia group was significantly better than the simple
      Pethidine group in the pain rating and pain score (P < 0.01); the incidence rate
      of abdominal pain at 1 h and 2-5 h after oocyte retrieval in the acupuncture
      compound anesthesia group was lower than that in the simple Pethidine group (P <
      0.01). CONCLUSION: In transvaginal ultrasound-guided oocyte retrieval,
      acupuncture compound anesthesia has the advances of safety, high effectiveness,
      rapid recovery after oocyte retrieval, and few side effects.

PMID- 18630548
TI  - [Study on original meaning and application of "Gen, Liu, Zhu, Ru"].
AB  - To probe into the original meaning and clinical application of "Gen, Liu, Zhu,
      Ru" in Miraculous Pivot * Genjie, based on Huangdi's Internal Classic and other
      opinions of annotation experts of successive dynasties, deeply analyze and study.
      The results indicate that two characteristics of "Gen, Liu, Zhu, Ru": similar to
      Maikou (the position to feel pulse in ancient Chinese medical classics); closely
      related to blood collaterals. It is suggested that "Gen, Liu, Zhu, Ru" can be
      used to diagnose disorder of meridians, and to treat the excess syndrome of
      meridians and collaterals with reducing method, including bleeding method.

PMID- 18630549
TI  - [Comparative study on Chinese medicine and western medicine for treatment of
      osteoarthritis of the knee in Caucasian patients].
AB  - OBJECTIVE: To compare the efficacy, safety and tolerability of different
      therapies in Caucasian patients with osteoarthritis (QA) of the knee. METHODS:
      Seventy-five cases (90 knee joints) of osteoarthritis were randomly divided into
      3 groups, western medicine group, traditional Chinese medicine (TCM) group,
      integrated Chinese and western medicine group. The western medicine group were
      treated with oral administration of Glucosamine Sulfate, oral administration and
      external application of non-steroid anti-inflammatory agent, ultrasound
      physiotherapy, etc. The TCM group were treated with oral administration of J
      uanbi Decoction, acupuncture and moxibustion, cupping, massage of acupoint and
      ear acupuncture. The integrated Chinese and western medicine group were treated
      with oral administration of Glucosamine Sulfate, oral administration and external
      application of non-steroid anti-inflammatory agent, acupuncture and moxibustion,
      cupping, massage of acupoint and ear acupuncture. The intensity of knee joint
      pain on walking, resting and standing, the nocturnal pain, stiffness, the maximum
      walking distance and the daily living ability were monitored after 30 days, 60
      days and 90 days of treatment. RESULTS: After 90 days of treatment, the
      integrated Chinese and western medicine group was better than other two groups in
      improvement of percentages in self pain assessment with visual analog scale
      (VAS), pain and stiffness measured by WOMAC scale, pain and maximum walking
      distance measured by Lequesne scale (P < 0.05 or P < 0.01). There were no
      significant differences in the therapeutic effects between the TCM group and the
      western medicine group. All of these three treatments were well tolerated, and no
      severe adverse events were found. CONCLUSION: Combined TCM and western medicine
      treatment has rapid and definite therapeutic effect in reducing pain and
      improving mobility of knee joints and daily living ability in Caucasian patients
      of knee osteoarthritis.

PMID- 18630550
TI  - [Survey of studies on the mechanism of acupuncture and moxibustion treating
      diseases abroad].
AB  - Acupuncture is a medical technique with national and cultural characteristics in
      traditional Chinese medicine with a less adverse reaction and obvious therapeutic
      effect. Modern medical theoretical basis about acupuncture treating many diseases
      is preliminarily discovered accompanying with the combination of traditional
      Chinese medicine and western medicine. This paper reviewed advances of the
      studies on the mechanisms of acupuncture treatment, and acupuncture treating
      pain, nausea and vomiting, neurodegenerative diseases, cerebrovascular and
      cardiovascular diseases and so on in recent years abroad.

PMID- 18630551
TI  - [Study on the theory of "Shaoyang Meridians being in charge of the bone"].
AB  - To explore the theory of "Shaoyang Meridians being in charge of the bone" in
      Huangdi's Internal Classic, which has been buried for long time. With citation of
      Huangdi's Internal Classic and exposition of famous experts, speculate on the
      contents and meanings systematically. Results indicate that the theory of
      "Shaoyang Meridians being in charge of the bone" possibly first in the world
      recognizes osteoporosis being a general bony disease, and articulates that the
      Foot-Shaoyang Meradians can modulate bony strength under physiological and
      pathological conditions, and treat osteoporosis which mainly manifests as
      ostealgia and easy fracture.

PMID- 18630552
TI  - [Combination surface shaded display with multiplanar reconstruction in the
      evaluation of acetabular morphologies in patients with developmental dysplasia of
      the hip before total hip arthroplasty].
AB  - OBJECTIVE: To explore the methods and application value of surface shaded display
      (SSD) and multiplanar reconstruction (MPR) in the evaluation of acetabular
      morphology in patients with developmental dysplasia of the hip (DDH) before total
      hip arthroplasty (THA). METHODS: From October 2003 to November 2006, 17 patients
      (3 males and 14 females, aging from 35 years to 61 years) with osteoarthritis
      secondary to DDH were scanned with spiral CT preoperatively. According to the
      Crowe standard, 19 dysplasia hips were classified as type I in 4 hips, type II in
      9 hips, type III in 6 hips. The obtained hip CT data were developed with SSD and
      MPR to observe spatial position and bone stock of the acetabula. RESULTS: The
      dislocated extent was 25%-89% in these dysplasia hips according to the Crowe
      method and their sharp angles all exceeded 45 degrees. Bone defect occurred to
      each of the acetabula, among which it was located in anterosuperior acetabulum in
      5 hips, in superolateral acetabulum in 11 hips and in posterosuperior acetabulum
      in 3 hips. The hip images made with MPR showed that the minimum thickness of the
      medial wall of acetabula ranged from 2.0 mm to 10.9 mm. Among 15 unilateral
      dysplasia patients, the opening difference and depth difference between the
      dysplasia acetabulum and the contralateral one ranged from 2.7 mm to 19.1 mm and
      from 2.3 mm to 13.1 mm, respectively. CONCLUSION: SSD and MPR of spiral CT are
      effective methods in evaluating acetabular morphology preoperation and contribute
      to intraoperative acetabular reconstruction in patients with DDH performed THA.

PMID- 18630553
TI  - [Total hip arthroplasty for the treatment of developmental dysplasia of the hip
      in adults].
AB  - OBJECTIVE: To summarize techniques of the total hip arthroplasty (THA) in the
      treatment of developmental dysplasia of the hip (DDH) with severe osteoarthritis
      in adults. METHODS: From March 2000 to January 2006, 24 patients (27 hips) with
      DDH were treated by THA with an cementless cup. There were 7 males and 17
      females, with the average age of 49.6 years (ranging from 26 years to 63 years).
      Unilateral DDH occurred in 21 patients and bilateral DDH occurred in 3 patients.
      Based on the Crowe classification, there were 16 hips in 15 patients of type I, 4
      hips in 4 patients of type II, 4 hips in 3 patients of type III, 3 hips in 2
      patients of type IV. Except for 3 patients with bilateral DDH, the other
      patients' ill lower limbs were 2-7 cm shorter than the healthy lower ones.
      RESULTS: All the patients were followed up from 9 months to 6.5 years and no one
      had infection, dislocation, femur fracture and so on after the operation. In 18
      patients, the pain was completely relieved and the function of the hip joints was
      good. After the gluteus medius exercise, the claudication of 3 patients after the
      operation disappeared. In 3 patients, the ill lower limbs were more than 1 cm
      shorter than the healthy lower ones and the other patients' ill lower limbs were
      less than 1 cm shorter than the healthy lower ones. Two patients' lower limbs
      were been lengthened 4-5 cm. All the patients' sciatic nerves were not injured.
      The Harris scores were 46.5 +/- 7.2 preoperatively and 84.0 +/- 5.7
      postoperatively (P < 0.05). CONCLUSION: THA with deepening the medial wall of the
      acetabulum at the true acetabulum and choosing small cementless cup in adult
      could obtain favorable results.

PMID- 18630554
TI  - [Cementless total hip arthroplasty for developmental dislocation of the hip in
      adults].
AB  - OBJECTIVE: To evaluate the operative technique and the short-term clinical effect
      of cementless total hip arthroplasty (THA) for developmental dislocation of the
      hip in adults. METHODS: From December 1997 to October 2006, 61 patients (78 hips)
      with developmental dislocation of the hip were treated with the cementless THA.
      There were 8 males and 53 females with the average age of 31.4 years (ranging
      from 17 years to 56 years). According to the classification of Hartofilakidis, 15
      cases were type I (18 hips), 23 type II (31hips), and 23 type III (29 hips). All
      the patients were exposed through the posterolateral approach. The threaded cup
      with coating was put at or near the level of the true acetabulum in all cases.
      Full coating stems were used in femoral sides, and shortening osteotomy below
      trochanter of femur was performed in 12 cases. RESULTS: Sixty patients (76 hips)
      were followed up with the mean duration of 49 months (range 12 to 118 months).
      All the hips of osteotomy and bone ingrowth acquired union 3 to 14 months after
      the operation. No patient had radiographic evidence of aseptic loosening of
      prosthesis. The average leg length of the hips with femoral shortening osteotomy
      was lengthened 2.0 to 4.5 cm. All patients had pain relief and no obvious motion
      limitation, limp gait and pelvic obliquity. The Harris scores were 40.28 +/- 9.84
      preoperatively and 90.92 +/- 2.80 postoperatively (P < 0.001). One patient with
      postoperative femoral nerve palsy completely recovered 4 months after the
      operation. CONCLUSION: Cementless THA for developmental dislocation of the hip in
      adults produces significantly better results, although it presents great
      technical difficulties.

PMID- 18630555
TI  - [Treatment of osteoarthritis secondary to acetabular dysplasia by total hip
      arthroplasty].
AB  - OBJECTIVE: To evaluate the flexibility of the treatment of osteoarthritis
      secondary to acetabular dysplasia by total hip arthroplasty (THA), in which the
      acetabular component is placed in the true acetabulum and femoral osteotomy is
      not performed. METHODS: From January 1999 to December 2005, 35 THA procedures
      were performed in 32 patients with 35 hips, including 6 males with 7 hips and 26
      females with 28 hips, with the average age of 53 years (ranging from 28 years to
      72 years). On the basis of Crowe classification, type I included 10 patients with
      11 hips, type II included 14 patients with 15 hips, type III included 5 patients
      with 6 hips, and type IV included 3 patients with 3 hips. All patients
      experienced severe pain and dysfunction. In 19 cases, the leg length discrepancy
      was from 3 cm to 6 cm. The Harris score was 41.49 +/- 10.13 before the operation.
      In all procedures, the soft tissue was released entirely and the acetabular
      component was placed in the true acetabulum, but femoral osteotomy was not
      performed. RESULTS: The average operation time of unilateral THA was 50 minutes.
      All patients were given transfusion from 2 U to 4U. All incisions healed at the
      first stage. After the operation, the leg was lengthened 2-6 cm, and the two legs
      were equally long. The follow-up lasted for 12 to 60 months. The Harris score was
      84.71 +/- 9.34 after the operation, showing statistically significant difference
      (P < 0.05). According to clinical outcomes and X-ray films, no dislocation,
      femoral fracture, femoral or sciatic nerve palsy was detected. CONCLUSION: It is
      effective to use THA procedures for osteoarthritis secondary to acetabular
      dysplasia. If the soft tissue is released entirely, the leg will be lengthened 4
      6 cm without nerve palsy.

PMID- 18630556
TI  - [A study of acetabular development after closed reduction in developmental
      dislocation of the hip].
AB  - OBJECTIVE: Through a retrospective study, to observe the clinical therapeutic
      effect for closed reduction treatment of developmental dislocation of the hip
      (DDH), and to dynamically analyze characteristics of acetabular development after
      closed reduction in DDH. METHODS: A total of 100 single side DDH children who
      were treated by "the treatment mode of closed reduction" from January 2002 to
      December 2005 were followed up, including 18 males and 82 females, with the
      average age of 19.4 months (ranging from 7 months to 36 months). Sixty-eight
      patients had left side dislocation, while 32 had right side dislocation.
      According to Zionts dislocation grades, 15 cases were degree I, 50 degree II, 26
      degree III and 9 degree IV. Adductor tenotomies and skeletal traction were
      carried out in 74 cases, while direct closed reduction was performed in 26 cases.
      The four-level functional evaluation criterion was used to assess the clinical
      therapeutic effect. Lesional and homeochronous normal hips were paired, and
      acetabular index (AI) and AI (D/W) of lesional and normal hips, before the
      reduction and in the 3rd, 6th, 9th and 12th month, respectively, after the
      reduction, were dynamically measured. RESULTS: The total choiceness rate of 100
      children was 88.00%. Twelve months after the reduction, lesional AI decreased
      from (37.17 +/- 2.17) degrees to (27.02 +/- 3.54) degrees, while lesional AI
      (D/W) increased from 22.06% +/- 1.65% to 29.80% +/- 3.56%, and the differences
      among each time-point had statistical significance (P < 0.01). Both rates of
      lesional AI decrease and AI (D/W) increase were obviously faster than those of
      normal side physiological development (P < 0.01). In all durations after 12
      months reduction, the rates of lesional AI were (3.22 +/- 1.42) degrees and (3.41
      +/- 2.03) degrees in 1-3 months and 10-12 months , respectively, and the rates of
      AI (D/W) were 2.69% +/- 1.83% and 2.33% +/- 1.13%, respectively, and they were
      obviously faster than the other durations (P < 0.01). Both rates of lesional AI
      decrease and AI (D/W) increase were obviously faster than the homeochronous rate
      of normal side physiological development in each duration (P < 0.01). The rates
      of lesional AI were (13.71 +/- 3.96) degrees and (11.48 +/- 4.15) degrees in 7-12
      age group and 13-18 age group, respectively, and the rates of AI (D/W) were 9.95%
      +/- 3.81% and 8.28% +/- 3.58%, respectively, and they were obviously faster than
      the other age groups (P < 0.05). Both changes of lesional AI and AI (D/W) were
      obviously faster than the homeochronous changes of normal side in each age
      group(P < 0.01). CONCLUSION: There are simple operating requirements and fine
      therapeutic effect of "the treatment mode of closed reduction" . Within 12-month
      after the closed reduction treatment, the rate of lesional acetabular development
      is obviously faster than that of normal side physiological development. The crest
      time of lesional acetabular development is during 1-3 months and 10-12 months,
      and the best treatment time of closed reduction is the age before 18 months.

PMID- 18630557
TI  - [Prevention and treatment of leg length discrepancy after total hip
      arthroplasty].
AB  - OBJECTIVE: To explore the prevention and treatment of leg length discrepancy
      after total hip arthroplasty (THA). METHODS: There were 87 patients who were
      treated by THA from January 2004 to December 2006, including 36 males and 51
      females, with the average age of 60.2 years (ranging from 35 years to 78 years).
      Among these cases, there were 35 of avascular necrosis of the femoral head, 38 of
      subcapital femoral neck fracture, 4 of femoral neck tumor, 6 of rheumatoid
      arthritis and 4 of acetabular dysplasia. In 70 cases, the patients had leg length
      discrepancy, and the legs shortened from 1 cm to 6 cm. Based on the clinical
      measurement and radiographic examination, the surgical protocols were designed,
      the type of the hip prosthesis was chosen, and the neck length of the femoral
      prosthesis and the position of osteotomy were estimated. By the proper wearing of
      the acetabula, the best rotation point was found out. The cut plane of the
      femoral neck was adjusted according to the results of the radiographic and other
      examinations. The neck length was readjusted after the insertion of the
      prosthesis so as to achieve intended leg-length equalization. The discrepancy of
      the leg length was measured and evaluated after operation. RESULTS: Superficial
      infestation happened in 2 cases 5 days after the operation and was cured by mero
      drainage. Luxation happened in 4 cases 4 weeks after the operation, in which 2
      cases were cured by operation while the other 2 were cured by manual reduction.
      All the patients were followed up for 6 months to 36 months, with the average
      time of 18.3 months. The Harris scores were 34.81 +/- 1.36 preoperatively and
      91.50 +/- 1.87 postoperatively (P < 0.05). In the 17 patients with equal legs
      before the operation, 1 was lengthened 1.5 cm in the leg, while in the 70
      patients with shortened legs before the operation, 66 returned to the same length
      in their legs, and 4 were lengthened or shortened from 1.6 cm to 2.1 cm. The
      total rate of equal leg length was 94.25%. CONCLUSION: The preoperative
      measurement, radiographic templating and intraoperative correction, together with
      postoperative orthopraxy, are effective in prevention and treatment of leg length
      discrepancy after THA.

PMID- 18630558
TI  - [Progress of hip resurfacing arthroplasty].
AB  - OBJECTIVE: To review the recent progress of hip resurfacing arthroplasty.
      METHODS: Literature concerning hip resurfacing arthroplasty and current
      achievements was extensively and comprehensively reviewed. RESULTS: The new metal
      on-metal hip resurfacing arthroplasty made much progress especially in materials
      and technology, and the results were satisfactory for short-term follow-up. This
      was increasingly widely used especially in treating young patients. But there
      were still some problems such as elevation of metal ions which had already
      aroused public attention. CONCLUSION: The new metal-on-metal hip resurfacing
      arthroplasty is an efficient method in the treatment of adult hip joint disease
      and has an encouraging future, but long-term follow-up is still needed.

PMID- 18630559
TI  - [Mid-term therapeutic effect analysis of cementless total knee arthroplasty
      without patella replacement].
AB  - OBJECTIVE: To explore the flexibility and reliability of cementless total knee
      arthroplasty (TKA) without patella replacement through a retrospective study of
      the mid-term therapeutic effect of the treatment of the patients. METHODS: From
      June 1997 to March 2000, a consecutive series of 152 (152 knees) cementless TKA
      performed in Hessing-Stiftung was studied. Among them, there were 63 males and 89
      females, with 70 left knees and 82 right knees. Their ages ranged from 51 years
      to 72 years, with an average of 59 years. There were 146 cases of osteoarthritis
      and 6 cases of traumatic arthritis. The course of the disease lasted for 1.0
      years to 3.5 years. The EFK prostheses of German Plus company were used in all
      the cases. The HSS score before the operation was 41.5 +/- 12.3, and the average
      range of motion was 55 degrees (ranging from 30 degrees to 90 degrees). RESULTS:
      Five patients underwent anterior knee pain, and the pain was released after the
      appropriate treatment. No deep infection happened in all cases. A total of 145
      patients (145 knees) were followed up for 5 years to 8 years. The HSS score was
      87.5 +/- 8.2 at the end of the follow-up, showing significant difference (P <
      0.05). The average range of motion was 95 degrees (ranging from 90 degrees to 110
      degrees). Partial radiolucencies occurred at the tibia side in 18 knees 3 to 6
      months after the operation. Among them, the width was less than 2 mm in 15 knees
      without symptom, and more than 2 mm in 3 knees. There were 2 of the 3 knees which
      were revised at the tibia side because of the aseptic loosing, while 1 patient
      had only mild pain in the knee during the follow-up, with no sign of loosing.
      CONCLUSION: The mid-term effect of cementless TKA is satisfactory. The ingrowth
      of femur and tibial bones is reliable. The early stage migration of the component
      is the main reason of loosing. Satisfying outcomes can also be achieved without
      patella replacement during TKA.

PMID- 18630560
TI  - [Clinical effect of arthroscopically assisted repair and reconstruction for
      dislocation of the knee with multiple ligament injuries].
AB  - OBJECTIVE: To investigate the clinical outcomes of the treatment of knee
      dislocation with multiple ligaments injuries by anterior cruciate ligament (ACL)
      and posterior cruciate ligament (PCL) reconstruction under arthroscopy and repair
      of the injured structures of the knee joint. METHODS: From July 2003 to August
      2006, there were 24 patients with knee dislocation (19 males and 5 females), with
      the average age of 42 years (ranging from 20 years to 69 years), whose ACL and
      PCL were reconstructed under arthroscopy and whose collateral ligaments and other
      structures of the knee were repaired [8 with injuries of ACL, PCL, medial
      collateral ligament (MCL) and lateral collateral ligament (LCL); 12 with injuries
      of ACL, PCL and MCL; 4 with injuries of ACL, PCL and LCL]. There were 1 case with
      common peroneal nerve injury, 3 with medial meniscus injury and 7 with lateral
      meniscus injury. Every patient had single knee dislocation. The outcome was
      measured from the following aspects: range of the knee, complication, clinical
      improvement and Lysholm scoring. RESULTS: Twenty-four patients were followed up
      for 11 months to 36 months, with the average time of 25 months. Eleven patients
      (45.8%) recovered to the normal sports level and 13 (54.2%) patients' knee
      function improved significantly so that they could walk by themselves. Lachman
      test, anterior drawer test and posterior drawer test were negative in 24
      patients. The side-to-side difference was less than 5 mm in 24 patients. There
      were 4 patients who had slight knee stiffness. One patient's feeling and sports
      function of the general peroneal nerve improved to the normal level. Lysholm
      scale of the knee function was 41.8 +/- 4.3 preoperatively and 87.0 +/- 6.0
      postoperatively (P < 0.05). The movement ranges of the knee were (87.5 +/- 12.5)
      degrees preoperatively and (125.0 +/- 9.2) degrees postoperatively (P < 0.05).
      CONCLUSION: Reconstructing the ACL and PCL and repairing other structures of the
      knee is an effective method to treat dislocation of the knee.

PMID- 18630561
TI  - [Comparison between four-strand semitendinosus tendon autograft and ligament
      advanced reinforcement system for anterior cruciate ligament reconstruction by
      arthroscopy].
AB  - OBJECTIVE: To compare the therapeutic effect of anterior cruciate ligament (ACL)
      reconstruction by means of four-strand semitendinosus tendon autograft and
      ligament advanced reinforcement system (LARS) by arthroscopy. METHODS: From July
      2002 to April 2005, 42 patients underwent ACL reconstruction by arthroscopy.
      Twenty-seven patients were treated by four-strand semitendinosus tendon autograft
      (semitendinosus tendon autograft group), including 22 males and 5 females, with
      the age from 20 years to 52 years. Among these patients, there were 12 sports
      injuries, 8 traffic accidents and 7 other injuries. There were 16 cases of left
      knees and 11 of right knees. The pre-operation Lysholm score was 50.70 +/- 6.68,
      and the course of the disease was 2 to 12 months. Other 15 patients were treated
      by LARS artificial ligament (LARS group), including 12 males and 3 females, with
      the age from 17 years to 40 years. Among these patients, there were 8 sports
      injuries, 4 traffic accidents and 3 other injuries. There were 6 cases of left
      knees and 9 of right knees. The pre-operation Lysholm score was 50.20 +/- 6.22,
      and the course of the disease was 3 to 12 months. There was no statistically
      significant difference between the two groups (P > 0.05). The ranges of motion,
      stability and complication of the knee were evaluated during the follow-up.
      RESULTS: All incisions healed at the first stage. The patients in the
      semitendinosus tendon autograft group were followed up for 22 months to 43
      months, while 18 months to 40 months in the LARS group. There were 5 patients
      (19%) whose tensile gap was more than 3 mm when the max tensile force text was
      done in the semitendinosus tendon autograft group, and 3 patients (20%) in the
      LARS group. The Lysholm score was 87.80 +/- 3.41 in the semitendinosus tendon
      autograft autograft group, and 88.90 +/- 3.30 in the LARS group. There was no
      statistically significant difference between the two groups (P > 0.05). The final
      evaluation based on the improved Lysholm classification standard showed the
      choiceness rate was 92.6% (18 excellent cases, 7 good cases and 2 fair cases) in
      the semitendinosus tendon autograft group, and 93.3% (11 excellent cases, 3 good
      cases, 1 fair case) in the LARS group. There was no statistically significant
      difference between the two groups (P > 0.05). The joint motion capability
      evaluation, according to the Tegner standard, showed 3 to 6 class (with the
      average class of 4.93) in the semitendinosus tendon autograft group, and 3 to 7
      class (with the average class of 5.03) in the LARS group. There was no
      statistically significant difference (P > 0.05). The knee extension in 2 cases
      was 5 degrees less than the normal, and in 5 cases 5-10 degrees less than the
      normal in the semitendinosus tendon autograft group. But in all cases in the LARS
      group, joint motion recovered to the normal (P < 0.05). There was no sign of
      synovitis in both groups. CONCLUSION: The recent clinical result of ACL
      reconstruction with the four-strand semitendinosus tendon autograft or LARS
      artificial ligament by arthroscopy is satisfactory without significant
      difference. LARS can shorten the recovery time without complications such as
      synovitis in 2-year follow-up.

PMID- 18630562
TI  - [Repair and reconstruction for severe fracture and dislocation of ankle joint].
AB  - OBJECTIVE: To summarize the technique and effect of the therapy for severe
      fracture and dislocation of ankle joint by operation. METHODS: From March 2003 to
      February 2006, 76 cases were treated with primary open restoration and internal
      fixation for dislocated ankle joint fracture, with 47 males and 29 females, with
      the average age of 36.4 years (ranging from 18 years to 65 years). According to
      AO criterion, these fresh fractures were classified into 13 cases for type C3-1,
      45 cases for type C3-2 and 18 cases for type C3-3. Based on the Gustilo-Anderson
      standard, 23 open fractures were classified into 17 cases for type II and 6 cases
      for type III A. The operation was delayed from 1 hours to 24 hours after the
      injury. RESULTS: All incisions healed at the first stage except 4 cases which
      delayed union because of simple infection by revision with ointment. A total of
      72 cases were followed up, with the average time of 18.5 months (from 12 months
      to 35 months). The time of bone union was from 12 weeks to 24 weeks. The screws
      of fixation for lower tibia-fibula joint were found to be ruptured in 2 cases
      when further consultation was performed in the 16th and 20th week after the
      operation, respectively, and were broken within 1 year after the operation. These
      screws were taken out 12 weeks postoperative in 28 cases, while the whole
      internal fixations of the rest cases were taken out 1 year after the operation.
      The postoperative function of malleolus extended from 21.7 degrees to 26.8
      degrees and flection from 38.5 degrees to 44.7 degrees. Assessed by the American
      Orthopaedic Foot and Ankle Society Clinical Rating Scales, 23 cases were
      excellent, 36 good, 13 fair, and the choiceness rate reached 81.94%. CONCLUSION:
      These procedures, together with reduction by twist after hospital, open and
      internal fixation in time, and parenchyma managed with internal fixation, are
      important to attain satisfactory effect for the treatment of severe fracture and
      dislocation of ankle joint.

PMID- 18630563
TI  - [Biomechanical evaluation of stability of the volar capsular ligament complex].
AB  - OBJECTIVE: To investigate the effect of the volar capsular ligament complex on
      stability of the wrist joint and to provide basic biomechanical theoretical
      criteria for clinic application of the external fixator. METHODS: Nine upper
      limbs specimens (left 6, right 3) were taken from fresh adult cadavers to make
      wrist joint-bone capsular ligament complex specimens. Firstly, soft tissues of
      forearms and hands were resected and capsular membranes and ligaments were
      reserved to make the bone-articular ligament complex (normal specimen). Secondly,
      the volar capsular ligament complex was cut off from radial malleolus to ulnar
      malleolus (impaired specimen). Thirdly, the impaired volar capsular ligament
      complex was uninterruptedly sutured by the use of 4# suture silk (repaired
      specimen). To simulate clinical operation with external fixator, the
      biomechanical test was done according to the sequence (normal, impaired,
      repaired, repaired and fixed, impaired and fixed). Statistical significance was
      analyzed through selected loads at the three different shifts (1.5, 2.0, 2.5 cm).
      RESULTS: According to the sequence (normal, impaired, repaired, repaired and
      fixed, impaired and fixed), when the shift was 1.5 cm, the different respective
      loads were (60.74 +/- 20.60), (35.23 +/- 13.88), (44.36 +/- 20.78), (168.40 +/-
      29.21) and (139.00 +/- 33.18) N, respectively. When the shift was 2.0 cm, the
      different loads were (138.46 +/- 12.93), (87.17 +/- 24.22), (97.52 +/- 23.29),
      (289.00 +/- 54.29) and (257.98 +/- 55.74) N, respectively. When the shift was 2.5
      cm, the different loads were (312.87 +/- 37.15), (198.16 +/- 37.14), (225.66 +/-
      30.96), (543.15 +/- 74.33) and (450.35 +/- 29.38) N, respectively. There was no
      statistically significant difference between the impaired and repaired specimens
      (P > 0.05). Similarly, there was statistically significant difference among the
      rest specimens (P < 0.05). The same statistical results were obtained when the
      two different shifts were compared. There was statistically significant
      difference at the three different shifts for the same specimen (P < 0.05).
      CONCLUSION: Volar capsular ligament complex is an important anatomic structure to
      keep stability of the wrist joint. The carpal instability arises out of the
      injured complex. Repairing the injured complex only can not immediately restore
      stability of the wrist joint. The external fixator can effectively help to
      diminish the relative shift of the impaired capsular ligament complex, to reduce
      the load of the repaired complex and to protect the complex accordingly. The
      device plays an important role in maintaining stability of the wrist joint.

PMID- 18630564
TI  - [3-D adjustable design of humeral prosthesis].
AB  - OBJECTIVE: To study the shoulder anatomy characteristics of the Chinese people
      and to design a new kind of humeral prosthesis, which could realize the
      adjustment in three-dimensional space and be adjusted repeatedly, based on
      Chinese humeral anatomy characteristics. METHODS: A double-gear structure as a
      rotating part was adopted to design the structure of this new kind humeral
      prosthesis. RESULTS: The humeral prosthesis could satisfy both the needs of
      Chinese individual shoulder characteristics and the Westerners' demands.
      CONCLUSION: A novel concept of shoulder prosthesis design with a strong
      application value in design and development of the new prosthesis is proposed.

PMID- 18630565
TI  - [Treatment of intertrochanteric comminuted fracture in aged patients by
      replacement of artificial long-stem bipolar femoral head].
AB  - OBJECTIVE: To discuss the clinical effect of hip arthroplasty for the treatment
      of intertrochanteric comminuted fracture in aged patients. METHODS: From February
      2004 to March 2006, 89 cases with intertrochanteric comminuted fractures were
      treated by replacement of artificial long-stem bipolar hip hemiarthroplasty with
      bone cement, including 34 males and 55 females, with the average age of 82.6
      years (ranging from 70 years to 92 years). There were fresh fractures in 76 cases
      and old fractures in 13 cases. According to improving-classification of Evans
      Jensen, there were 32 cases with type III fracture and 57 with type IV.
      Osteoporosis was graded by Singh-index, and there were 24 cases with level IV, 46
      with level III and 19 with level II. The operation was delayed from 4 days to 36
      days (6.5 days on average) after the injury. RESULTS: The surgery time lasted
      from 50 minutes to 70 minutes (62 minutes on average). Bleeding volume was from
      100 mL to 250 mL (150 mL on average). The time in hospital was from 16 days to 25
      days (18.6 days on average). All incision primarily healed except 1 case which
      delayed union by revision with infection. Steel wire rupture occurred in 1 case,
      invalidation in 1 case. They were not treated because there were no uncomfortable
      symptoms. The consciousness disability happened in 2 cases 2 to 3 days after the
      operation, 2 case with the infection for the system of urine and breath 1 week
      after operation, were healed through the treatment. Eighty-five cases were
      followed up for 14 months to 39 months (26.5 months on average). The function of
      the hip was graded by the system of Harris and the choiceness rate was 84.7%
      (excellent in 16 cases, good in 56 cases, fair in 12 cases and poor in 1 case).
      CONCLUSION: The treatment of intertrochanteric comminuted fracture in the aged
      patients by replacement of long-stem bipolar femoral head prosthesis is
      effective, but indications and techniques of the operation must be paid much
      attention to.

PMID- 18630566
TI  - [Application of auto-control micro-motion intramedullary locking nail in the
      treatment of femoral shaft fractures].
AB  - OBJECTIVE: The auto-control micro-motion intramedullary locking nail (AMLN) is
      designed, to reduce the incidence of delayed union and non-union of femoral shaft
      fractures fixed by interlocking intramedullary nails, and to observe the clinical
      effect of self-design AMLN in the treatment of femoral shaft fractures. METHODS:
      The distal and promixal nails were connected by the micro-motion locking
      structure, which could cause 1.0-1.5 mm axial micro-motion between fracture gaps.
      It could produce physical stimulus and conduction between fracture gaps in the
      course of fracture union. From December 2003 to May 2006, 32 cases of femoral
      shaft fractures were treated with AMLN, including 21 males and 11 females with
      the average age of 31.2 years (ranging from 20 years to 43 years). The trauma
      resulted from fall wounds in 3 cases, crash injuries in 1 case and car accidents
      in 28 cases. Twenty-nine cases were fresh fractures in different parts of the
      femoral shaft with transverse, oblique, spiral and comminuted fractures of type
      I, II, III and IV. Three cases were old non-union fractures. The fresh fractures
      were treated by closed AMLN fixation, while the old fractures were treated by
      open AMLN nails after routine implantation of self bone. RESULTS: All the 32
      cases were followed up for the average time of 11.5 months (ranging from 8 months
      to 22 months). The X-ray films showed the fractures were healed 4.0 to 7.5 months
      after the operation, with the mean time of 5.1 months, and no break of the nail
      happened. One nail mildly bent in the comminuted fracture, and 2 patients felt
      slightly unwell at the needling point. According to the Klemm criterion for
      function, 26 cases were excellent, 5 good, 1 fair, and the choiceness rate was
      96.88%. CONCLUSION: With a suitable design, AMLN is easy to perform and helpful
      to quicken fracture union, and it is effective to treat femoral shaft fractures.

PMID- 18630567
TI  - [Femoral shaft fracture treated with closed reduction and intramedullary
      nailing].
AB  - OBJECTIVE: To discuss the techniques and advantages of closed reduction and
      intramedullary nailing in treating femoral shaft fracture without cannulated
      femoral reamer. METHODS: From January 2006 to June 2007, 24 cases of femoral
      shaft fracture were treated with closed reduction and intramedullary nailing.
      Among them, there were 14 males and 10 females, with the average age of 38.3
      years (ranging from 18 years to 63 years), with 7 left legs and 17 right legs.
      The average course of the disease was 7.6 days (ranging from 3 days to 20 days).
      According to the AO typing, there were 5 cases of type A, 6 of type B, 7 of type
      C1, 2 of type C2 and 4 of type C3. Closed reduction was achieved with
      manipulation and reaming of femoral canal was instructed by fluoroscopy. RESULTS:
      The operation time lasted from 100 minutes to 170 minutes, with the average time
      of 128.3 minutes. One patient was given a transfusion of 400 mL, and others were
      not. Twenty cases were followed up with the average time of 13.1 months (ranging
      from 6 months to 24 months). A mild to large amount of bony callus was showed on
      X-ray films 6 to 12 weeks postoperatively. Walking without crutches began at the
      average week of 22.2 (ranging from 15 to 30) postoperatively. Range of motion of
      the knee was 0 degrees to 145.5 degrees. No infection or break of the internal
      fixator occurred. Myositis ossificans with pain and insufficient flexion of hip
      (120 degrees) happened in 1 case and the pain disappeared after non-steroid anti
      inflammatory drugs were taken. Nonsymptomatic myositis ossificans occurred in 2
      cases and no treatment was needed. CONCLUSION: Closed reduction and
      intramedullary nailing can help to protect the blood supply of fracture fragments
      and provide central fixation. The operation process will be more complicated if
      cannulated femoral reamer is not available.

PMID- 18630568
TI  - [Biomechanical test of intramedullary controlled dynamic nailing].
AB  - OBJECTIVE: To explore the biomechanical properties of a new intramedullary
      controlled dynamic nailing (ICDN). METHODS: Ten pairs of specimens of adult
      femurs, with the age of 18 to 55 years, were divided into two groups (groups Al
      and B2, n = 10). The length of the specimens was (438 +/- 10) mm , and the
      external diameter was (26.4 +/- 1.5) mm. The specimens of the two groups were
      osteotomized transversely after the biomechanical test. ICDNs and GK nails were
      randomly implanted into the femurs, respectively (groups A2 and B2). Torsional,
      bending and axial compressive tests were made in each group, and the effect of
      dynamic compression between the fracture fragments was tested. RESULTS: The
      resistance to compression of groups A1, B1, A2 and B2 were (0.19 +/- 0.18) x
      10(6), (0.22 +/- 0.12) x 10(6), (1.67 +/- 0.68) x 10(6) and (0.86 +/- 0.32) x
      10(6) N/mm, respectively. There was statistically significant difference between
      groups A2 and B2 (P < 0.01). The bending stiffnesses of coronal section of groups
      A1, B1, A2 and B2 were (0.94 +/- 0.25) x 10(3), (1.10 +/- 0.21) x 10(3), (0.70 +/
      0.22) x 10(3), (0.64 +/- 0.21) x 10(3) N/mm, respectively. The bending stiffness
      of sagittal plane of groups A1, B1, A2 and B2 were (1.06 +/- 0.26) x 10(3), (0.96
      +/- 0.25) x 10(3), (0.67 +/- 0.25) x 10(3), (0.61 +/- 0.18) x 10(3) N/mm,
      respectively. There were no statistically significant differences between groups
      A1 and B1 or between groups A2 and B2 (P > 0.05). When the torque was 5 Nm, the
      torsional stiffness of groups A1, B1, A2 and B2 were (4.00 +/- 2.54), (4.76 +/-
      1.93), (0.50 +/- 0.63), (0.35 +/- 0.31) Nm/degrees, respectively. When the torque
      was 8Nm, the torsional stiffness of groups A1, B1, A2 and B2 were (4.30 +/-
      3.27), (3.94 +/- 2.01), (0.42 +/- 0.52), (0.36 +/- 0.18) Nm/degrees,
      respectively. There were statistically significant differences between groups A1
      and A2 or between groups B1 and B2 (P < 0.05), and no statistically significant
      difference between between groups A2 and B2 (P > 0.05). The average maximal
      pressure generated between the fracture fragments which were fixed with ICDN was
      21.6 N, and the pressure between the fracture fragments which were fixed with GK
      nailing could not be tested. CONCLUSION: The design of ICDN conforms to the
      special anatomical structure of the femur. ICDN could provide a completely
      different structure, a different fixation principal and a more balanced fixation
      than GK nail. ICDN incorporates the flexible and rigid fixation, which is likely
      to be the trend of the fracture fixation.

PMID- 18630569
TI  - [A biomechanical study of stability of atlantoaxial junction fixation with
      anterior approach screw fixation through C2 vertebral body to C1 lateral mass and
      Gallie's technique].
AB  - OBJECTIVE: To determine the three-dimensional stability of atlantoaxial
      reconstruction with anterior approach screw fixation through C2 vertebral body to
      C1 lateral mass and Gallie's technique (ASMG) for C1,2 instability. METHODS:
      Twenty-five human cadaveric specimens (C0-3 ) were divided randomly into 5 groups
      (n = 5). The three-dimensional ranges of motion C relative to C2 were measured
      under the five different conditions: the intact state group (group A), type II
      odontoid fracture group (group B), posterior C1,2 transarticular screw fixation
      group (group C), ASM group (group D) and ASMG group (group E). The three
      dimensional ranges of motions C1 relative to C2 by loading +/- 1.5 Nm were
      measured under the six conditions of flexion/extension, left/right lateral
      bending, and left/right axial rotation. The obtained data was statistically
      analyzed. RESULTS: In each group, the three-dimensional ranges of motion C1
      relative to C2 under the six conditions of flexion/extension, left/right lateral
      bending, and left/right axial rotation were as follows: in group A (8.10 +/-
      1.08), (8.49 +/- 0.82), (4.79 +/- 0.47), (4.93 +/- 0.34), (28.20 +/- 0.64),
      (29.30 +/- 0.84) degrees; in group B (13.60 +/- 1.25), (13.80 +/- 0.77), (9.64 +/
      0.53), (9.23 +/- 0.41), (34.90 +/- 0.93), (34.90 +/- 1.30) degrees; in group C
      (1.62 +/- 0.10), (1.90 +/- 0.34), (1.25 +/- 0.13), (1.37 +/- 0.28), (0.97 +/-
      0.14), (1.01 +/- 0.17) degrees; in group D (2.03 +/- 0.26), (2.34 +/- 0.49),
      (1.54 +/- 0.22), (1.53 +/- 0.30), (0.80 +/- 0.35), (0.76 +/- 0.30) degrees; in
      group E (0.35 +/- 0.12), (0.56 +/- 0.34), (0.44 +/- 0.15), (0.55 +/- 0.16), (0.43
      +/- 0.07), (0.29 +/- 0.06) degrees. Under the six conditions, there were
      generally significant differences between group A and other four groups, and
      between group B and groups C, D and E (P < 0.001), and between group E and groups
      C, D in flexion/ extension and left/right lateral bending (P < 0.05). There was
      no significant difference between group E and groups C, D in left/right axial
      rotation (P > 0.05). CONCLUSION: In vivo biomechanical studies show that ASMG
      operation has unique superiority in the reconstruction of the atlantoaxial
      stability, especially in controlling stability of flexion/extension and
      left/right lateral bending, and thus it ensures successful fusion of the
      implanted bone. It is a reliable surgical choice for the treatment of the
      obsolete instability or dislocation of C1,2 joint.

PMID- 18630570
TI  - [Posterior approach to treatment of spinal stenosis associated with degenerative
      lumbar scoliosis].
AB  - OBJECTIVE: To discuss the main points of techniques and ranges of fusion in
      posterior operation of degenerated lumbar scoliosis complicated spinal stenosis.
      METHODS: From February 2001 to September 2006, 23 cases with degenerated lumbar
      scoliosis stenosis were treated by posterior operation. There were 9 males and 14
      females, with the average age of 65.3 years (ranging from 52 years to 71 years).
      The course of the diseases was 4 to 8 years. All patients were presented with
      severe low back pain. All patients were measured for Cobb angle of curves(17
      degrees to 53 degrees), and lordosis angle of lumbar (-20 degrees to 10 degrees
      10 cases, -40 degrees to -20 degrees 13 cases). Ten cases in which Cobb angle was
      smaller than 20 degrees were operated by limited segmental decompression of
      spinal canal, posterior intervertebral fusion and short transpedical instrument
      fixation. For the rest 13 cases in which Cobb angle was bigger than 20 degrees
      were operated by canal decompression, longer instrument for scoliosis correction,
      intervertebral fusion and posterior-lateral fusion. The fixation and fusion were
      located at L4-S1 in 6 cases, L1-5, in 5, L2-5 in 4, L1-S1 in 5, L2-S1 in 2 and
      T10-S1 in 1. RESULTS: There was no patient who died from the operation. Average
      Cobb angle in coronal plane was 0 degrees to 21 degrees with the average of 15.6
      degrees. The lumbar lordosis angle was -48.0 degrees to -18.2 degrees with the
      average of 36.4 degrees. There were 21 cases (91%) with sciatica and intermittent
      claudication who were clearly released. There were 20 cases (87%) whose low back
      pain intensely decreased. Three cases with drop-foot returned to normal
      activities. During the mean 15-month (6 to 54 months) follow-up for 23 cases,
      there was no change of corrected results and fusion rate was 100%. CONCLUSION:
      For degenerated lumbar scoliosis patients, the most important purpose of the
      treatment is to improve clinical symptoms through sufficient decompression of
      neural structures. Lumbar stabilization reconstruction and benign spinal
      biomechanics line conduct to long-term curative effect. Overall estimate of the
      clinical appearances and imageology characters is necessary when the decision,
      that segments are needed to be fixed and fused should be made. The strategy of
      the individualized treatment may be the best choice.

PMID- 18630571
TI  - [Surgical management of dural injuries and postoperative cerebrospinal fluid
      fistulas in spinal surgeries].
AB  - OBJECTIVE: To investigate the surgical management of dural injuries and
      postoperative cerebrospinal fluid (CSF) fistulas in spinal surgeries and to
      observe clinical outcomes, since intraoperative injury of dura mater and
      postoperative CSF fistulas are common complications of spinal surgeries. METHODS:
      A retrospective research was designed and 405 patients with complete data who
      underwent spinal surgeries between June 2002 and March 2006 were acquired,
      including 298 cases of male and 107 cases of female, with the mean age of 46.2
      years (ranging from 11 years to 78 years). The course of disease lasted from 3
      months to 5 years. A total of 28 cases of intraoperative dural injuries and
      durotomies (28/405, 6.91%) were recorded, including 3 cases of cervical spinal
      surgery (3/152, 1.97%), 19 cases of thoracic and lumbar spinal surgery (19/239,
      7.95%) and 6 cases of sacral surgery (6/14, 42.86%). CSF fistulas occurred in 6
      cases of 28 patients. There were 2 cases in which no intraoperative dural injury
      was detected but CSF fistulas occurred after operation. The incidence of
      postoperative CSF fistula was 1.98% (8/405). Surgical management included closure
      of breach in the dura mater, oversewing every layer of the wound, bed rest and
      compression dressing and so on. Clinical outcomes of surgical management were
      recorded. RESULTS: The average follow-up lasted for 1 year and 5 months (ranging
      from 3 months to 4 years). Preoperative symptoms remitted to different extents.
      There were 8 cases of postoperative CSF fistula which were cured ultimately. A
      total of 6 cases of CSF fistulas from dorsal injuries of dura mater were treated
      mainly by bed rest, compression dressing and reoperations, while 2 cases of
      fistulas from ventral and lateral injuries of dura mater were treated by
      additional continuous cerebrospinal fluid drainage using a lumbar subarachnoid
      catheter. One case of central nervous system infection occurred and was treated
      successfully by multi-disciplinary disposal. CONCLUSION: Timely and correct
      surgical intervention and postoperative management can help to heal dural
      injuries in spinal surgeries and can prevent occurrence of postoperative CSF
      fistulas.

PMID- 18630572
TI  - [An experimental study of establishment of physiological reflex arc after conus
      medullary injury in rats].
AB  - OBJECTIVE: To establish an artificial physiological reflex arc with
      reconstruction of the sensory and the motorial functions of atonic bladder
      simultaneously after the conus medullary injury in rats. METHODS: Twenty 3-month
      old male SD rats, with the weight of 250 to 300 g, were included. The right side
      was the experimental side, while the left side served as a control. Intradural
      microanastomosis of the right L5 ventral root to S2 ventral root and L5 dorsal
      root to S2 dorsal root was performed to reconstruct the sensory and the motorial
      functions of atonic bladder. After axonal regeneration, the new motor-to-motor
      and sensory-to-sensory artificial bladder reflex pathway was established. At 5
      months postoperatively, the early function of the reflex arc was observed by
      electrophysiological examinations, and the bladder pressure was tested. RESULTS:
      Eighteen rats survived for 5 months after the operation. Single stimuli (3 mA,
      0.3 ms) of the S2 dorsal root of the experimental side resulted in evoked
      potentials recorded from the right vesical plexus before and after the spinal
      cord was destroyed horizontally between L6 and S4 segmental levels. The
      amplitudes of the evoked potentials were (0.10 +/- 0.02) mV and (0.11 +/- 0.03)
      mV, respectively, before and after paraplegia, and there was no statistically
      significant difference (P > 0.05). The figures of the evoked potentials were
      similar to those of the control side. Bladder contraction was initiated by trains
      of stimuli (3 mA, 20 Hz, 5 s) of the S2 dorsal root of the experimental side. The
      bladder pressures were (6.55 +/- 1.33) cmH2O and (6.11 +/- 2.01) cmH2O,
      respectively, and the amplitudes of bladder smooth muscle complex action
      potential were (0.11 +/- 0.02) mV and (0.11 +/- 0.03) mV, respectively, before
      and after paraplegia. There was no significant difference (P > 0.05). These
      figures were similar to those of the control side before paraplegia. Before
      paraplegia, when the S2 dorsal root of the control side was stimulated, the
      amplitude of the evoked potential was (0.14 +/- 0.02) mV, the bladder pressures
      was (10.77 +/- 1.78) cmH2O and the amplitude of bladder smooth muscle complex
      action potential was (0.17 +/- 0.02) mV. There was statistically significant
      difference between the experimental side and the control side (P < 0.01). All the
      results of electrophysiological examinations and bladder pressure were negative
      when the left S2 dorsal root was stimulated after paraplegia. CONCLUSION:
      Suprasacral nerve motor-to-motor and sensory-to-sensory transfers after the
      spinal cord injury to reconstruct the bladder autonomic reflex arc by intradural
      microanastomosis of ventral root and the dorsal root between L5 and S2
      simultaneously is practical in a rat model and may have potential in clinical
      application.

PMID- 18630573
TI  - [Clinical application of free peroneal perforator-based sural
      neurofasciocutaneous flap].
AB  - OBJECTIVE: To investigate the operative techniques and clinical results of
      repairing the soft tissue defects of forearm and hand with free peroneal
      perforator-based sural neurofasciocutaneous flap. METHODS: From May 2006 to
      January 2007, 6 patients including 5 males and 1 female were treated. Their ages
      ranged from 22 years to 51 years. They were injured by motor vehicle accidents (2
      cases), or crushed by machines (4 cases), with skin defect of hand in 1 case,
      skin defect of hand associated with tendon injuries and metacarpal fractures in 2
      cases, skin defect of forearm in 2 cases, and forearm skin defects with fractures
      of radius and ulna in 1 case. The areas of soft tissue defect ranged from 16 cm x
      7 cm to 24 cm x 10 cm. The debridement and the primary treatment to tendons or
      bones were performed on emergency. And free flaps were transplanted when the
      wound areas were stable at 4 to 7 days after the emergent treatment. During the
      operation, the flaps were designed along the axis of the sural nerve nutrient
      vessels according to the shape and size of the soft tissue defects, with the
      peroneal perforator above the lateral malleolus as the pedicle and along with a
      part of the peroneal artery for vascular anastomosis. Then the flaps were
      harvested and transferred to the recipient sites with the peroneal varley
      anastomosed to the radial (or ulnar) artery and the peroneal veins to one of the
      radial (or ulnar) veins and the cephalic vein, respectively. The flap size ranged
      from 18 cm x 8 cm to 25 cm x 12 cm. The donor areas were closed by skin grafts.
      RESULTS: The 5 flaps survived after the surgery. Partial inadequate venous return
      and distal superficial necrosis happened in only 1 case, which also got secondary
      healing by changing dressing and anti-infective therapy. The donor sites reached
      primary healing completely. The followed-up in all the patients for 6 to 13
      months revealed that the appearance and function of the flaps were all
      satisfactory, and no influence on ambulation of donor site was found. CONCLUSION:
      Peroneal perforator-based sural neurofasciocutaneous flap has the advantages of
      favourable appearance, constant vascular pedicle, reliable blood supply, large
      size of elevation and minor influence on the donor site. And the free transfer of
      this flap is an ideal procedure to repair the large soft tissue defects of
      forearm and hand.

PMID- 18630574
TI  - [A clinic study of transverse rectus abdominis myocutaneous flap in immediate
      breast reconstruction with refined breast incisions of breast mastectomy].
AB  - OBJECTIVE: To discuss the aesthetic effect and application of refined incisions
      in breast reconstruction for breast cancer patients by the transverse rectus
      abdominis myocutaneous (TRAM) flap. METHODS: From January 2001 to October 2006,
      77 cases with breast cancer were treated with TRAM flap to immediate breast
      reconstruction. The patients were all females, with an average age of 45 years
      (ranging from 26 years to 53 years). There were 39 cases of left breast and 38
      cases of right breast. The disease course was from 1 day to 180 days. There were
      11 cases of stage I, 60 cases of stage II and 6 cases of stage III, among which
      34 cases were located in the upper outer quadrant, 15 in the lower outer
      quadrant, 22 in the upper inner quadrant and 6 in the lower inner quadrant. The
      size of tumors varied from 1 cm to 4 cm. As to the pathologic type, 60 cases were
      invasive ductal cancers, 12 ductal cancers in situ, 5 invasive lobular cancers;
      positive lymph node (number: 1-7) happened in 29 cases, while negative lymph node
      happened in 48 cases. Among the 77 cases, regular shuttle incisions were
      performed in 35 cases, and refined circle incisions were performed in 42 cases,
      which were 2 cm away from the breast tumor border. Axillary incision was
      necessary for the breast tumors located in upper inner, lower inner and upper
      outer quadrants in order to perform axillary mastectomy. Ten cases were nipple
      areola sparing. The shape, symmetry and incision scar of the reconstructed breast
      were evaluated and graded. RESULTS: There were 6 cases out of 77 cases of breast
      reconstruction in which partial necrosis happened and the necrosis rate was
      7.79%. The time of follow-up was from 13 months to72 months, with an average of
      39 months. No recurrence or metastasis happened in 76 cases, and distant
      metastasis happened only in 1 case. There were 40 cases out of 42 cases with
      refined incisions which were scored more than 3, and the satisfaction rate was
      95.24%. There were 31 cases out of 35 cases with regular incisions which were
      scored more than 3, and the satisfaction rate was 88.57%. CONCLUSION: The
      reasonable refined incision based on the location of the tumor is effective to
      improve the satisfaction rate for the shape of the reconstructed breast.

PMID- 18630575
TI  - [Carrier combination of tissue engineered bone by sodium alginate and xenograft
      bone and bone formation in vivo].
AB  - OBJECTIVE: To produce a new bone tissue engineered carrier through combination of
      xenograft bone (X) and sodium alginate (A) and to investigate the biological
      character of the cells in the carrier and the ability of bone-forming in vivo, so
      as to provide experimental evidence for a more effective carrier. METHODS: BMSCs
      were extracted from 2-week-old New Zealand rabbits and the BMSCs were induced by
      rhBMP-2 (1 x 10(-8)mol/L). The second generation of the induced BMSCs was
      combined with 1% (V/W) A by final concentration of 1 x 10(5)/mL. After 4-day
      culture, cells in gel were investigated by HE staining. The second generation of
      the induced BMSCs was divided into the DMEM gel group and the DMEM containing 1%
      A group. They were seeded into 48 well-cultivated cell clusters by final
      concentration of 1 x 10(5)/mL. Seven days later, the BMP-2 expressions of BMSCs
      in A and in commonly-cultivated cells were compared. The second generation of the
      induced BMSCs was mixed with 2% A DMEM at a final concentration of 1 x 10(10)/mL.
      Then it was compounded with the no antigen X under negative pressure. After 4
      days, cells growth was observed under SEM. Twenty-four nude mice were randomly
      divided into 2 groups (n = 12). The compound of BMSCs-A-X (experimental group)
      and BMSCs-X (control group) with BMSCs whose final concentration was 1 x
      10(10)/mL was implanted in muscles of nude mice. Bone formation of the compound
      was histologically evaluated by Image Analysis System 2 and 4 weeks after the
      operation, respectively. RESULTS: Cells suspended in A and grew plump. Cell
      division and nuclear fission were found. Under the microscope, normal
      proliferation, many forming processes, larger nucleus, clear nucleolus and more
      nuclear fission could be seen. BMP-2 expression in the DMEM gel group was 44.10%
      +/- 3.02% and in the DMEM containing 1% A group was 42.40% +/- 4.83%. There was
      no statistically significant difference between the two groups (P > 0.05). A was
      compounded evenly in the micropore of X and cells suspended in A 3-dimensionally
      with matrix secretion. At 2 weeks after the implantation, according to Image
      Analysis System, the compound of BMSCs-A-X was 5.26% +/- 0.24% of the total area
      and the cartilage-like tissue was 7.31% +/- 0.32% in the experimental group; the
      compound of BMSCs-X was 2.16% +/- 0.22% of the total area and the cartilage-like
      tissue was 2.31% +/- 0.21% in the control group. There was statistically
      significant difference between the two groups (P < 0.05). At 4 weeks after the
      operation, the compound of BMSCs-A-X was 7.26% +/- 0.26% of the total area and
      the cartilage-like tissue was 9.31% +/- 0.31% in the experimental group; the
      compound of BMSCs-X was 2.26% +/- 0.28% of the total area and the cartilage-like
      tissue was 3.31% +/- 0.26% in the control group. There was statistically
      significant difference between the two groups (P < 0.05). CONCLUSION: The new
      carrier compounding A and no antigen X conforms to the superstructural principle
      of tissue engineering, with maximum cells load. BMSCs behave well in the compound
      carrier with efficient bone formation in vivo.

PMID- 18630576
TI  - [Interventional effect of platelet lysate on osteogenic differentiation of BMSCs
      in rats].
AB  - OBJECTIVE: To explore the interventional effect of platelet lysate (PL) on
      osteogenic differentiation of BMSCs by induction in rats in vitro. METHODS:
      Twenty-four clean-grade adult Wistar rats, weighing from 250 g to 300 g, male or
      female, were included in this study. PL was obtained through three times of
      centrifugation and repeated freeze-thaw for the blood aspirated from cardiac
      cavities in 16 Wistar rats. ELISA assay was conducted to detect the concentration
      of growth factors PDGF, TGF-beta1, IGF-1 and VEGF in PL. The BMSCs harvested by
      flushing femurs of 8 adult Wistar rats were isolated, cultivated and expanded in
      vitro. The cells at the 4 passage were performed for osteogenic differentiation
      by induction in three groups of A (5% PL of final concentration in basic
      induction medium), B (1% PL of final concentration in basic induction medium),
      and C (no presence of PL in basic induction medium as a control). The
      morphological changes of the cells were dynamically observed with inverted phase
      contrast microscope during the whole period. At different time-points, ALP
      staining (7 days) and ALP/TP (2, 8, 12 days) of the cells were detected to
      evaluate ALP activity, and the mineral formation in extracellular matrix was
      examined with Alizarin red staining which provided quantitative analysis of
      mineral deposits. RESULTS: ELISA assay showed that the content of PDGF, TGF
      beta1, IGF-1 and VEGF in PL reached (300 +/- 30), (140 +/- 25), (80 +/- 35), (70
      +/- 20) pg/mL, respectively. Morphological observation displayed BMSCs in group A
      or B gradually turned from spindle-shape to square- or polygon-shape as the
      morphological type of osteoblast-like cells at 7 days. The cells in group A
      showed slower shape changes but higher proliferation than that in group B or C.
      Moreover, at the 20 days, the cells in group A still displayed dense growth and
      produced obviously decreased amount of mineral deposits in ECM when compared with
      group B or C. At the 7 days, the cells of group A showed smaller amount of
      granules positive for ALP staining in cytoplasm when compared with groups B and
      C, and displayed marked reduction in ALP activity assay at the 2, 8, and 10 days
      compared with that of groups B and C (P < 0.05). At the 20 days, Alizarin red
      staining showed the number of mineral deposits in groups A, B and C were 7.67 +/-
      1.10, 12.87 +/- 0.81 and 15.59 +/- 0.25, respectively, while the area of mineral
      deposits were (161 778.70 +/- 44 550.80), (337 349.70 +/- 56 083.24), and (415
      921.70 +/- 71 725.39) pixels, respectively. The number of mineral deposits and
      the area of mineral deposits in group A were smaller than those in groups B and C
      (P < 0.05). But there was no statistically significant difference between groups
      B and C (P > 0.05). CONCLUSION: PL is a kind of system carrying various growth
      factors. Exposure of PL inhibits both ALP activity and mineral formation of BMCs
      in a dose-dependent way under the osteogenic induction environment.

PMID- 18630577
TI  - [An experimental study of coculture of esophageal mucosa epithelial cells with
      SIS and their biological characteristics].
AB  - OBJECTIVE: To explore an effective method to cultivate esophageal mucosa
      epithelial cells (EMECs) of canine in vitro, and to observe the biological
      characteristics of EMECs growing on SIS in order to provide an experimental basis
      for esophagus tissue engineering. METHODS: Esophageal tissues were obtained from
      five healthy dogs aged 2 to 5 weeks under sterile conditions. The primary EMECs
      were cultivated with defined keratinocyte serum free medium (DKSFM) containing 6%
      FBS. The morphological characteristics and the growth curve of EMECs of the 2nd
      generation were observed for 1 to 5 days. The expressions of the EMECs marker
      (cytokeratin 19, CK-19) were examined by immunocytochemistry. The 2nd generation
      of EMECs was seeded on SIS and observed by HE staining, immunohistochemical
      staining, and SEM for 4 and 8 days. RESULTS: The primary culture of canine EMECs
      arranged like slabstone. Immunohistochemical staining of CK-19 of the 2nd
      generation EMECs showed positive broadly. The cells growth reached the peak level
      at 2 days by MTT method. EMECs were polygon in shape and arranged like slabstone,
      and formed a single layer on the surface of SIS. The cells were contacted closely
      with each other for 4 days. Eight days later, 2 to 3 layers stratified structure
      was formed. Lots of EMECs were grown on SIS, and showed laminate arrangement.
      CONCLUSION: With mixed enzymatic digestion, the culture of EMECs in DKSFM
      containing 6% FBS is a simple and feasible method. SIS shows good
      biocompatibility and can be used as a good scaffold material in the tissue
      engineered esophagus.

PMID- 18630578
TI  - [Research on in vitro differentiation of human umbilical cord blood-derived CD34+
      cells into hepatocyte-like cells].
AB  - OBJECTIVE: To observe the effect of cytokines and combinations in the inducement
      of human umbilical cord blood-derived CD34+ cells into hepatocyte-like cells.
      METHODS: The mononuclear cells (MNCs) were derived by density gradient
      centrifugation and the CD34+ cells were separated from MNCs. The human umbilical
      cord blood-derived CD34+ cells were cultivated through 49 different combinations
      of cytokines including leukemia inhibitor factor (LIF), oncostatin M, bFGF, aFGF,
      hepatocyte growth factor, EGF and stem cell factor for 28 days, and the
      concentrations of the cytokines were 10, 10, 10, 10, 20, 20 and 50 ng/mL,
      respectively. The mRNAs of cytokeratin 19 (CK-19), CK-18, glutamine synthetase
      (GS), human albumin (ALB) and alpha-fetoprotein (AFP) were detected every seven
      days. The ALB secretion ability, detoxification ability and hepatic synthesis
      ability of the induced cells were detected by immunofluorescence assay,
      indocyanine green (ICG) and periodic acid-schiff assay, respectively. The fresh
      umbilical cord blood-derived CD34+ cells were detected at the same time as a
      control. RESULTS: The mRNAs of CK-19, CK-18 and GS could be transcribed in all
      the induced cells, but the transcription of the mRNAs of ALB and AFP which was
      the special mark of mature hepatocyte and liver stem cell, respectively, was not
      found. All the mRNAs could not be found in freshly isolated umbilical cord blood
      derived CD34+ cells. All the cells induced in vitro could not release ALB, and
      not help the detoxification of ICG which was the fundamental function of mature
      liver cells. These results were the same in the control group. The hepatic
      synthesis ability of all the induced cells increased by comparison to the fresh
      ones. CONCLUSION: Though some mRNAs of proteins which are transcribed in
      hepatocytes can be found in the induced cells, umbilical cord blood-derived CD34+
      cells could not be transdifferentiated into hepatocyte-like cells through
      cytokines in vitro.

PMID- 18630579
TI  - [An experimental study of the role of myosin light chain in myogenesis in vitro].
AB  - OBJECTIVE: To investigate the role of myosin light chain (Myl) in myogenesis in
      vitro. METHODS: The extraocular muscle, diaphragm and gastrocnemius muscle
      myoblasts (eMb, dMb and gMb) were isolated and purified from 12 3-week-old
      C57BL/6 mice by using the enzyme digestion and Preplate technique, and then were
      subcultivated. The Myl expression in Mb was detected by RT-PCR and Western blot
      analysis; the Mb proliferation activity was tested by methylene blue assay, and
      the myotube formation was observed. After anti-Myl antibody (1, 2, 3, 8, 16
      ng/mL) was induced in the Mb culture (experimental group), the ability of
      proliferation of myoblasts and the myotube formation were identified. Meanwhile,
      the Mb which was cultured without anti-Myl antibody was identified as the control
      group. RESULTS: The results of RT-PCR and Western blot analysis showed that Myl1
      and Myl4 mRNA and Myl protein were expressed in eMb, dMb and gMb at 24 hours
      after seeding, and their expression level were lower in eMb than in dMb and gMb
      (P < 0.01), and the latter two did not show any significant difference (P >
      0.05). Myl2 and Myl3 mRNA was not detected in these three myoblasts. The
      proliferation assay showed that the eMb proliferated faster as compared with dMb
      and gMb (P < 0.01). eMb began to yield myotubes at 40 hours after seeding and dMb
      and gMb at 16 hours after seeding. At 6 days, the number of myotubes derived from
      eMb was (137.2 +/- 24.5)/field, which was significantly larger than that of
      myotubes from dMb [(47.6 +/- 15.5)/field ] and gMb [(39.8 +/- 5.1)/ field ] (P <
      0.01). There was not statistically significant difference between the latter two
      groups (P > 0.05). After the antibody treatment, the absorbency values of the
      eMb, dMb and gMb in the experimental groups at each antibody concentration point
      were significantly higher than those in the corresponding control groups (P <
      0.05), and the dose-dependent way was performed. The numbers of myotubes from dMb
      at 16 hours were (48.2 +/- 7.1)/ well in the experimental group and (23.4 +/-
      4.9)/ well in the control group, and at 6 days were (40.6 +/- 10.2)/ field in the
      experimental group and (63.1 +/- 6.1)/ field in the control group. There was
      statistically significant difference between the experimental and control groups
      (P < 0.01). CONCLUSION: Myl may play a role in myogenesis through the negative
      effect on the myoblast proliferation.

PMID- 18630580
TI  - [Effects of electroacupuncture pretreatment on ischemic arrhythmia and
      intracellular calcium oscillation in single cardiocyte isolated from rats with
      myocardial ischemia and reperfusion].
AB  - OBJECTIVE: To observe the inhibitory effects of acupuncture pretreatment on
      arrhythmia and intracellular calcium ([Ca2+]i) oscillation in single cardiocyte
      in rats subjected to myocardial ischemia-reperfusion (MIR). METHODS: Male SD rats
      were evenly randomized into normal control (NC), MIR and electroacupuncture (EA)
      groups. MIR was performed by ligation (30 min) and reperfusion (10 min) of the
      left anterior descending coronary artery in vivo in rats or in the isolated and
      perfused rat heart subjected to a 40 min global ischemia followed by a 10 min
      reperfusion. EA pretreatment was applied to bilateral "Neiguan" (PC 6) for 30 min
      once a day in 3 consecutive days. Arrhythmic score was calculated according to
      Curtis's and Walker's method, and the count of [Ca2+]i oscillation was measured
      by using InCytPm 2 intracellular ion detecting system. RESULTS: Both the
      arrhythmic score and the count of [Ca2+]i oscillation in MIR group were
      considerably higher than those in NC group (P<0.05). While compared with MIR
      group, the arrhythmia score and the count of [Ca2+]i oscillation in EA group were
      decreased significantly (P<0.05). CONCLUSION: Pretreatment of EA can effectively
      resist MIR-induced arrhythmia and intracellular calcium oscillation in the rat.

PMID- 18630581
TI  - [Observation on the accumulative analgesic effect of electroacupuncture and the
      expression of protein kinase A in hypothalamus and hippocampus in chronic pain
      or/and ovariectomized rats].
AB  - OBJECTIVE: To observe the accumulative analgesic effect of electroacupuncture
      (EA) and the simultaneous changes of protein kinase A (PKA) expression in
      hypothalamus and hippocampus in rats with chronic constrictive injury (CCI)
      or/and learning-memory impairment. METHODS: Sixty-eight female Wistar rats were
      randomized into normal control, CCI, CCI + EA 2 d, CCI + EA 2 w, OVX + CCI, OVX +
      CCI + EA 2 d and OVX + CCI + EA 2 w groups, with 10 cases in each except OVX +
      CCI group (n=8). CCI pain model was established by ligature of the right sciatic
      nerve with surgical suture. EA (2/15 Hz, 1-2 mA, 30 min) was daily applied to
      bilateral "Zusanli" (ST 36) and "Yanglingquan" (GB 34) for 2 days (2 d) and 2
      weeks (2 w) respectively. Neuro-memory impairment was induced by OVX plus
      subcutaneous injection of D-galactose. Hyperalgesic scores (HS) were detected
      with radiation-heat irradiation and PKA activity was detected by
      immunohistochemical method. RESULTS: After CCI, HS of all groups increased
      significantly in comparison with normal control group (P<0.05). In simple CCI
      rats, compared with CCI group, HS of both CCI + EA 2 d and CCI + EA 2 w groups
      decreased markedly (P<0.05), and that of CCI + EA 2 w group was evidently lower
      than that of CCI + EA 2 d group on the 18th day after CCI (P<0.05). In memory
      impairment rats, HS of both OVX + CCI + EA 2 d and OVX + CCI + EA 2 w groups was
      significantly lower than that of OVX+ CCI group (P<0.05); and no significant
      difference was found between OVX + CCI + EA 2 w and OVX + CCI + EA 2 d groups in
      HS (P>0.05). Results of immunohistochemistry showed that the integral grey values
      (IGV) of PKA of paraventricular nucleus (PVN), arcuate nucleus (ARC) and
      supraoptic nucleus (SON) of hypothalamus in CCI + EA 2 w group were significantly
      lower than those in normal control and CCI + EA 2 d groups (P<0.05). IGV of PVN
      and SON in OVX + CCI + EA 2 w group were also markedly lower than those in OVX +
      CCI group (P<0.05), displaying upregulation and cumulative increase of PKA
      expression by EA 2 w. IGV of PKA, ARC and SON in OVX + CCI + EA 2 w group were
      markedly higher than those in CCI + EA 2 w group (P<0.05), suggesting an apparent
      attenuation of the cumulative upregulation effect of PKA expression after
      learning-memory injury. The changing tendency of PKA expression in hippocampal
      CA1 region was similar to that of SON after repeated EA of ST36 and GB34.
      CONCLUSION: Repeated EA has a cumulative analgesic effect in CCI rats, which is
      probably related to its resultant upregulation of PKA expression in neurons of
      hypothalamus and hippocampus and the animals' neuro-memory.

PMID- 18630582
TI  - [Effects of electroacupuncture of different acupoints on cardiac function in
      acute myocardial ischemia rabbits].
AB  - OBJECTIVE: To observe the effects of electroacupuncture (EA) of "Neiguan" (PC 6),
      "Shenmen" (HT 7), "Taiyuan" (LU 9), "Zhizheng" (SI 7) and "Sanyinjiao" (SP 6) on
      cardiac function in acute myocardial ischemia (AMI) rabbits. METHODS: A total of
      60 rabbits were randomly divided into normal control, model, EA-PC6, EA-HT7, EA
      LU9, EA-S17 and EA-SP6 groups. AMI model was established by intravenous
      administration of pituitrin. ECG, maximal ascending rate ( + dp/dt max) and
      maximal descending rate (- dp/dt max) of the left ventricular pressure, and left
      ventricular systolic pressure (LVSP) were recorded. RESULTS: The heart rate (HR),
      +dp/dt max, -dp/dt max and LVSP decreased significantly after AMI (P<0.01).
      Compared with model group, the 4 indexes of EA-PC6, EA-HT7 and EA-S17 groups
      increased considerably (P<0.05, 0.01) at most time-points after AMI, and the
      effects of EA-PC6 and EA-HT7 were markedly better than those of EA-SI7, EA-LU9
      and EA-SP6 (P<0.05, 0.01). No significant differences were found among model
      group, EA-LU9 and EA-SP6 groups in HR, + dp/dt max, -dp/dt max and LVSP at most
      time-points after AMI. CONCLUSION: EA of PC6, HT7 and SI7 has a good effect in
      improving ischemic cardiac performance, and the effect of PC6 and HT7 is markedly
      better than that of SI7. The effect of EA of SP6 and LU9 is poorer on ischemic
      cardiac function.

PMID- 18630583
TI  - [Effect of scalp-acupuncture on energy metabolism of brain tissue in
      intracerebral hemorrhage rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on mitochondrial SDH
      and Na+ -K+ -ATPase activity, and lactate acid (LA) content in the peri-hemotoma
      tissue in rats with intracerebral hemorrhage (ICH) so as to explore its
      mechanisms in resisting cerebral ischemia. METHODS: A total of 80 Wistar rats
      were randomized into normal group, sham group, model group, EA group. The last
      three groups were further divided into 24 h, 72 h and 168 h subgroups
      respectively, with 8 cases in each group/subgroups. ICH model was established by
      caudatum-injection (right) of Collagense VII/heparini solution (2 microl). EA (2
      Hz, 1 mA) was applied to "Baihui" (GV 20)-"Taiyang" (EX-HN 5) for 30 min.
      Chondriosome suspension of the cerebral perihemotoma tissue was got by gradient
      centrifugation for detecting SDH and Na+ -K+ -ATPase activity, and LA content
      with chromometry. RESULTS: In comparison with sham-operation group and control
      group, SDH and mitochondrial Na+ -K+ -ATPase activity in cerebral peri-hemotoma
      tissue declined significantly from 72 h and 24 h on respectively (P<0.05), while
      LA level increased markedly from 24 h on (P<0.05) in model group. Compared with
      sham-operation group, SDH activity (168 h) and Na+ -K+ -ATPase activity (24 h, 72
      h and 168 h) in EA group also decreased significantly (P<0.05); LA level (24 h,
      72 h) in EA group increased considerably (P<0.05). Whereas compared with model
      group, SDH and Na+ -K+ -ATPase activity increased significantly at most time
      courses (P<0.05), and LA level decreased remarkably (P<0.05) in EA group.
      CONCLUSION: EA can improve the energy metabolism, upregulate the activity of
      chondriosome,and reduce the accumulation of LA in the cerebral perihemotoma
      tissue of ICH rats.

PMID- 18630584
TI  - [Effects of electroacupuncture on plasma and cerebral somatostatin and beta-EP
      contents and learning-memory ability in vascular dementia rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on learning-memory
      ability of vascular dementia (VD) rats, and the simultaneous changes of plasma
      and cerebral somatostatin (SS) and beta-endorphin (EP) contents. METHODS: Forty
      one SD rats were randomly divided into control (n=8), model A (n=8, no treatment)
      and B (n=8, intragastric perfusion of 15% saline), EA (n=9) and medication (n=8,
      intragastric perfusion of Nimoldipine, 12 mg/kg) groups. VD model was established
      by using modified 4-vessels occlusion method. EA (150 Hz, 1-2 mA) was applied to
      "Baihui" (GV 20), "Dazhui" (DU 14), "Pishu" (BL 20) and "Shenshu" (BL 23) for 20
      min, once daily for 15 days. Morris water maze tests were conducted for
      evaluating the rats' learning-memory ability. The contents of SS and beta-EP in
      plasma and brain tissue were measured by radioimmunoassay (RIA). RESULTS: In
      comparison with sham-operation group, the escape latency (EL) prolonged
      significantly and the target-platform crossing times decreased remarkably
      (P<0.01) in model group B. In comparison with model group B, EL shortened and
      target-platform crossing times increased both significantly in EA and medication
      groups (P<0.01). Plasma and cerebral SS, and cerebral beta-EP contents of model
      groups A and B were significantly lower than those of sham-operation
      group(P<0.01), while plasma beta-EP level had no obvious change (P>0.05). Plasma
      and cerebral SS, and cerebral beta-EP contents in both EA and medication groups
      were considerably higher than those in model groups A and B (P<0.01). No
      significant differences were found between EA and medication groups in EL, target
      platform crossing times, plasma and cerebral SS and beta-EP levels, and between
      model group A and model group B in plasma and cerebral SS and beta-EP levels
      (P>0.05). CONCLUSION: EA can raise plasma and cerebral SS and cerebral beta-EP
      levels, and improve the learning-memory ability in VD rats.

PMID- 18630585
TI  - [Effect of electroacupuncture pretreatment on glutamate-NMDAR signal pathway in
      hippocampal neurons of vascular dementia rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on
      hippocampal glutamate (Glu) content and N-methyl-D-aspartate receptor (NMDAR)1
      mRNA expression in rats with vascular dementia (VD) so as to explore its
      underlying mechanism in improving VD. METHODS: A total of 72 SD rats were
      randomized into control (n=16), sham-operation (n=16), model (n=20) and EA
      pretreatment (n=20) groups. VD model was established by modified middle cerebral
      artery occlusion. EA (1 mA, 1.7 Hz) was applied to "Baihui" (GV 20), "Shenshu"(BL
      23) and "Zusanli" (ST 36), once daily for 10 days. Glu content of right
      hippocampus tissue was detected with chromatometry. NMDAR 1 mRNA expression of
      hippocampus was detected by in situ hybridization histochemistry. RESULTS: In
      comparison with sham operation group, Glu content and NMDAR 1 mRNA expression of
      hippocampus in model group increased significantly (P<0.01). Compared with model
      group, Glu content and NMDAR 1 mRNA expression of hippocampus in EA pretreatment
      group decreased significantly (P<0.01, 0.05). CONCLUSION: EA pretreatment can
      suppress the increase of Glu content, down-regulate NMDAR 1 mRNA expression in VD
      rats, which may contribute to its effect in relieving VD via reducing apoptosis
      and protecting cerebral neurons.

PMID- 18630586
TI  - [Effect of electroacupuncture on mitochondrial membrane potential and apoptosis
      in the cerebral cortex in rats with focal cerebral ischemia/reperfusion injury].
AB  - OBJECTIVE: To investigate the effect of electroacupuncture (EA) on mitochondrial
      membrane potential and neuronal apoptosis in the cerebral cortex of rats with
      focal cerebral ischemia/reperfusion (CI/R) injury. METHODS: Thirty-six male SD
      rats were uniformly randomized into sham operation (sham), CI/R and CI/R + EA
      groups. CI/R model was established by middle cerebral artery occlusion (MCAO) and
      reperfusion. EA (2/15 Hz, 1 mA) was applied to "Shuigou" (GV 26) and "Baihui" (GV
      20) for 30 min after CI/R. The mitochondrial membrane potential and neuronal
      apoptosis in the cerebral cortex (fronto-parietal lobes) in each group were
      detected by flow cytometer (FCM). RESULTS: In comparison with sham group, the
      mitochondrial membrane potential of CI/R group decreased significantly (P<0.01),
      while compared with CI/R group, it increased remarkably in CI/R + EA group
      (P<0.01). The percentage of neuronal apoptosis in CI/R group was significantly
      higher than that in sham group (P<0.01), and that of CI/R + EA group was
      significantly lower than that of CI/R group (P<0.01). CONCLUSION: EA can
      alleviate CI/R injury partially by up-regulating the mitochondrial membrane
      potential, which may contribute to its effect in reducing cerebral neuronal
      apoptosis.

PMID- 18630587
TI  - [Influence of electroacupuncture on insulin-resistance in nonalcoholic fatty
      liver rats].
AB  - OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in treating
      nonalcoholic fatty liver disease (NAFLD) in rats. METHODS: Thirty male SD rats
      were randomized into normal control, NAFLD model and EA groups, with 10 cases in
      each. NAFLD model was established by feeding the rats with high-fat food for 8
      weeks. EA (2 Hz, 4 mA) was applied to "Zusanli" (ST 36), "Fenglong" (ST 40),
      "Sanyinjiao" (SP 6), and "Taichong" (LR 3) for 15 min, once daily for 4 weeks.
      Fasting blood sugar (FBG) and serum free fatty acids (FFA) were detected with
      chromatometry; serum insulin (INS) was determined with radioimmunoassay;
      homeostasis model assessment insulin resistance (HOMA-IR) and liver index (LI)
      were calculated. Liver tissue was cut into sections for detecting pathological
      changes. RESULTS: Compared with normal control group, FBG, INS, FFA, HOMA-IR and
      LI of model group increased significantly (P<0.05), and hepatic diffuse steatosis
      with cellular necrosis and inflammatory cell infiltration was obvious. In
      comparison with model group, all the 5 indexes in EA group decreased
      significantly (P<0.05), and pathological changes as hepatic steatosis, etc. were
      significantly reduced. CONCLUSION: EA may be used to effectively improve NAFLD by
      lowering insulin resistance.

PMID- 18630588
TI  - [Effects of electroacupuncture on synovia free radicals in rabbits with knee
      osteoarthritis].
AB  - OBJECTIVE: To observe the effect of electroacupuncture( EA) on synovia superoxide
      dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) contents in
      rabbits with knee osteoarthritis (KOA). METHODS: A total of 40 New Zealand
      rabbits were randomly divided into control, model, massage and EA groups, with 10
      cases in each. KOA model was established by gypusum fixing method. EA (1.6-2 Hz,
      1-2 mA) was applied to left "Yanglingquan" (GB 34), "Xuehai" (SP 10), "Zusanli"
      (ST 36) and "Liangqiu" (ST 34) for 25 min, once daily for 21 days. For massage
      group, the affected knee joint was pressed, kneaded, stretched and rotated
      repeatedly for 15 min every time, followed by forced running about 100 m. The
      intra-joint synovia was collected (0.4-0.6 ml) for detecting contents of SOD with
      xanthine oxidase method, MDA with thiobarbituric acid method and NO with nitrate
      reductase method. RESULTS: Compared with control group, synovia SOD activity in
      model group decreased considerably (P<0.05), while MDA and NO contents increased
      significantly (P<0.05). After 3 weeks' treatment, compared with pre-treatment and
      model group, synovia SOD activity increased markedly (P<0.05), and MDA and NO
      contents lowered remarkably in both EA and massage groups (P<0.05). No
      significant differences were found between EA and massage groups in these 3
      indexes (P>0.05). CONCLUSION: Both EA and massage can raise synovia SOD activity
      and lower MDA and NO content, which may contribute to their effect in relieving
      knee osteoarthritis in the rabbit.

PMID- 18630589
TI  - [Effects of transcutaneous electric acupoint stimulation on plasma SOD and MDA in
      rats with sports fatigue].
AB  - OBJECTIVE: To observe the effect of transcutaneous electric acupoint stimulation
      (TEAS) on plasma superoxide dismutase (SOD) and malondialdehyde (MDA) in rats
      with sports fatigue so as to explore its mechanisms in resisting exercise-induced
      fatigue. METHODS: Twenty-seven male adult SD rats were randomly divided into
      control group (n 9), model group (n=9) and TEAS group (n=9). Sports fatigue model
      was established by using treadmill method, i.e. forcing the rat to run 10 min at
      a speed of 10 m/min, 15 m/min, 20 m/min, 24 m/min and 28 m/min, once daily for 6
      days. TEAS (continuous waves, 2 Hz, 5 mA) was applied to unilateral "Zusanli" (ST
      36) for 30 min, once per day for 7 days. The exhausted exercise time from
      starting running to exhaustion was recorded on the 7th day and the lactate
      levels, SOD activity and MDA contents in plasma were measured by lactate oxidase
      method, xanthine oxidase method and thiobarbituric acid method respectively.
      RESULTS: The duration of exhausted exercise in model group and TEAS group were
      (56.00 +/- 12.27) min and (70.88 +/- 13.74) min respectively, displaying
      significant increase in exercise tolerance after TEAS (P<0.05). The lactate level
      and MDA content in model group were markedly higher than those in control group
      (P<0.05); while compared with model group, lactate and MDA contents in TEAS group
      were significantly lower (P<0.05), and plasma SOD activity in TEAS group was
      significantly higher (P<0.01). No significant differences were found in plasma
      lactate content between control and TEAS groups and in SOD activity between model
      group and control group (P>0.05). SOD/MDA of model group was significantly lower
      than those of control group and TEAS group (P<0.05, 0.01). CONCLUSION: TEAS at
      "Zusanli"(ST 36) can effectively postpone exercise-induced fatigue by reducing
      accumulation of blood lactate, improving anti-oxidative ability and relieving
      lipid peroxidation in the rat.

PMID- 18630590
TI  - [Effects of strong and weak electroacupuncture on endotoxin-induced changes of
      electrical activities of heat-sensitive neurons in preoptic area and anterior
      hypothalamus in rabbits].
AB  - OBJECTIVE: To observe the effects of weak and strong electroacupuncture (EA) on
      endotoxin (ET) thermolysis-induced changes of discharges of neurons in the
      preoptic region and anterior hypothalamus (PO-AH) so as to explore its underlying
      mechanism in antipyretic and thermolytic actions and its relation to the
      receptive system of acupoints. METHODS: Eighteen New Zealand rabbits were
      randomly divided into ET group, ET + weak-EA group and ET + strong-EA group.
      Extracellular discharges of the PO-AH neurons were recorded by using tungsten
      microelectrodes. A "U"-shape stainless steel tube was implanted in the region
      (P0.4-A4.4, L0.5-1.7) crossing the hypothalamus for changing local temperature by
      perfusion of cool (25 degrees C) or warm (41 degrees C) solution in order to
      distinguish the heat sensitive neurons (HSN), cold sensitive neurons (CSN) and
      insensitve neurons to temperature changes. Intravenous injection of endotoxin (25
      EU/rabbit) was given to rabbits to induce increase of tempe rature. EA (8 Hz,
      wave width 0.1 ms, weak stimulation: 4.5 V, strong stimulation: 25 V) was applied
      to bilateral "Yongquan" (KI 1) for observing changes of firing rates of HSN in PO
      AH. RESULTS: Compared with the basal values of firing rates of PO-AH neurons in
      each group, the average changing ratios of both ET and ET + weak-EA groups
      decreased significantly from 55-60 min on in ET group and from 40-45 min on in ET
      + weak-EA group after intravenous injection of ET (P<0.05), suggesting no marked
      effect of weak EA for preventing discharges of PO-AH neurons from decrease. While
      in ET + strong-EA group, the firing rates of HSN of PO-AH kept stable after
      injection of ET during EA and after cease of EA (P>0.05 vs basal value),
      suggesting that strong EA could antagonize ET thermolysis-induced decrease of
      firing rates of PO-AH neurons. CONCLUSION: Stronger EA stimulation of KI1 can
      antagonize ET thermolysis-induced effect on electrical activities of PO-AH HSN,
      which may be initiated by the activation of the high-threshold thin nerve fibers
      in the acupoint region.

PMID- 18630591
TI  - [Clinical investigation on electroacupuncture treatment of vascular dementia with
      "Xiusanzhen"].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) in the treatment of
      vascular dementia (VD) so as to explore an effective therapy for it. METHODS:
      Sixty cases of VD were randomly divided into acupuncture group and medication
      (Duxil, 40 mg/time, 2 times/d for 10 weeks) group, with 30 cases in each group.
      "Xiusanzhen" means that two acupuncture needles were penetrated subcutaneously
      from bilateral Yingxiang (LI 20) to Shangyingxiang (EX-HN 8) respectively, and
      the 3rd needle was penetrated from the midpoint between two Yangbai (GB 14)
      through Yintang (EX-HN 3) to the nasal root, followed by applying EA stimulation
      to the acupoints. Hasegawa's Dementia Scale (HDS), Mini-mental state examination
      (MMSE), and Functional Activities Questionnaire (FAQ) were used for assessment of
      the VD patient's state before and after the treatment. RESULTS: After the
      treatment, the total effective rates of acupuncture and medication groups were
      80.00% and 73.33% respectively. The effective rate of acupuncture group was
      significantly superior to that of medication group (P<0.05). Before treatment,
      scores of HDS, MMSE and FAQ in both groups had no significant differences
      (P>0.05); after the treatment, the scores of HDS and MMSE increased
      significantly, and that of FAQ decreased remarkably in both groups (P<0.01), and
      the difference of scores (or absolute value of FAQ) between post-treatment and
      pre-treatment in EA group was obviously higher than that in medication group
      (P<0.05). CONCLUSION: Acupuncture of "Xiusanzhen" is effective in the treatment
      of VD patients.

PMID- 18630592
TI  - [Progress in researches on the specificity of acupoints].
AB  - In the present paper, the authors introduce the development of researches on the
      specificity of acupoints in morphological structure (nerves, blood vessels,
      musculotendons, connective tissues, etc), biophysical characteristics
      (electricity, sonics, photology, thermology, electromagnetism), pathological
      response, and effectiveness. However, the aforementioned researches are basically
      at the stage of phenomenon-observation, some key factors influencing acupoint
      specificity and the underlying mechanisms have no definite or lack convincing
      results. Further studies should aim at those acupoints for some effective
      diseases (or symptoms) of acupuncture by using multiple modern scientific
      techniques. Some key scientific issues about the biophysical characteristics,
      pathological responses, efficacy, and combination regularity of acupoints should
      be solved reasonably. Moreover, theoretical models about acupoint specificity
      should be established for developing the theory of acupoint learning.

PMID- 18630593
TI  - [Basic factors for inducing divarication about the location of some acupoints].
AB  - The curative effect of acupuncture depends much on accurate location of
      acupoints. But, in the developmental course of Chinese acu-moxibustion medicine,
      some divarications about the location of acupoints have occurred for ages. In the
      process of formulating international standard of acupoint location, experts from
      China, Japan and Korea had different viewpoints about the location of 92
      acupoints. After reviewing Chinese ancient and modern literatures, authors of the
      present paper sum up five basic factors influencing the location of acupoints:
      (1) different understandings about the bone-length; (2) changes of bone-length;
      (3) faults during copying literature; (4) different understandings on the
      location in the text of books; (5) evolvement of concepts. These viewpoints may
      be helpful to solve the divarication of acupoints' location.

PMID- 18630594
TI  - [Discussion on the Qi-passage of meridian-collateral system].
AB  - The author of the present paper holds that "Qi-passage" is in fact the essence of
      meridian-collateral system in the human body. In my opinion, the so called "Jing"
      of the fourteen meridians is referred to the tissue structure of the longitudinal
      fascia space; the so called "Luo" of the fifteen collaterals referred to the
      tissue structure of the transversal fascia space, and the "Mai" of meridians and
      collaterals referred to tissue liquid-Qi of both longitudinal and transversal
      fascia space. The "Dao" (Qi-passage) of meridians and collaterals is the tissue
      structure of both longitudinal and transversal fascia space. The tissue liquid-Qi
      and tissue structure depend on each other. The doctrine of "Qi-passage" of
      meridian-collateral system has its original evidence, scientific and substantive
      basis. The meridian-collateral system is a regulative and control system of the
      unknown synthetic functions of multiple substances including loose connective
      tissue, tissue liquid-Qi, energy substances, nerves, blood vessels and lymph,
      etc..

PMID- 18630596
TI  - [The relation between reg 1A mRNA expression and the clinicopathologic parameters
      in the patients with primary gastric carcinoma].
AB  - Using reverse transcriptase-polymerase chain reaction (RT-PCR), REG 1A mRNA
      expression was investigated in 235 primary gastric carcinoma samples. And the
      relation between these results with the clinicopathologic parameters of primary
      gastric carcinoma was discussed in experiment. The positive REG 1A mRNA is 78%
      (183/235) of primary gastric carcinoma which revealed by RT-PCR analysis.
      Moreover, patients with REG 1A-positive differentiated adenocarcinoma were found
      to have a significantly poorer prognosis compared with REG 1A-negative tumor
      patients. REG IA mRNA is closely linked to the infiltrative growth pattern and
      with signet ring cell carcinoma and poorly differentitated adencarcinoma. And the
      incidence of venous invasion of REG 1A-positive tumors was significantly higher
      than that of REG 1A-negative tumors. So the results of the experiment demonstrate
      that the expression of the REG 1A gene is closely related to the infiltrating
      property of primary gastric carcinoma, and may be as a prognostic indicator of
      differentiated adenocarcinoma of the stomach in clinic diagnosis.

PMID- 18630595
TI  - [A simple strategy for the rapid selection of effective antisense fragments
      targeting human genes].
AB  - Antisense RNAs have often been used to study functions of human genes. In order
      to obtain the effective antisense fragments, researchers always have to face
      repeated works including cell culture and transfection etc. Here we chose yeast,
      Saccharomyces cerevisiae, as a model organism to explore the simple and effective
      way to obtain antisense fragments targeting human genes. This single-cell
      eucaryote divides rapidly, can be cultured easily just as E. coli, and possesses
      many biological processes similar to mammalian. Thus, it is the best choice for
      the study focus on human gene transcription and other biological processes. Human
      Elongator complex was found to be very similar to the yeast Elongator both in
      composition and its interaction with RNA polymerase II. The elp3 subunit of human
      Elongator can significantly complement the growth defects of Yeast elp3 Delta
      Strain. So we used yeast complementation systems to select the antisense fragment
      targeting help3. Three different fragments including full length (a1 644), HAT
      deletion (a1 107) and HAT(a450) sequence of help3 were amplified and inserted
      into pRS313 or pRS314 to construct antisense plasmids pRS313a1 644, pRS314a1 107
      and pRS314a450. Through the sensitive assay and RT-PCR detection of help3 and
      ssa3 expression in yeast, we approved that the HAT-deletion fragment (a1 107)
      repressed the expression of cotransformed help3 significantly and reduced the
      complementation ability of help3 dramatically in yeast. Then the a1 107 antisense
      mammalian expressing plasmid was constructed and transfected into Hela cells.
      Northern blot assay indicated that a1 107 significantly reduced the expression of
      help3 in HeLa cells. So we regard that cotransforming targeting human gene and
      its antisense fragments into yeast and obtaining the significant reduction
      expression of targeting human gene is a simple strategy for the selection of
      antisense fragment targeting human genes.

PMID- 18630597
TI  - [Induction and in vitro culture of hairy roots of Solanum nigrum L. var.
      pauciflorum Liou and its solasodine production].
AB  - By using genetic transformation of Agrobacterium rhizogenes and liquid culture,
      induction and culture conditions for Solanum nigrum L. var. pauciflorum Liou
      hairy roots and its solasodine production and consumption changes of N resource
      and calcium in the medium during liquid culture were investigated. The results
      showed that hairy roots could be initiated from the cut edges of leaf explants 5
      days after inoculation with the strain of A. rhizogenes ATCC15834. The percentage
      of rooted leaf explants 25 days after infection was more than 90%. Hairy roots
      could grow rapidly on solid or liquid growth regulator-free MS medium. The PCR
      amplification of rol genes and virC gene showed that rol genes of Ri plasmid of
      A. rhizogenes were integrated in the genome of transformed hairy roots of S.
      nigrum L var pauciflorum. The hairy roots could produce medicinal secondary
      metabolites solasodine and the amount of solasodine in the hairy root cultures
      reached a level of 582.05 microg/g dry weight and was 1.31 times as much as those
      in the untransformed roots. The hairy roots grew very slowly in 0-5 days in the
      liquid medium, then, very fast from 5 to 15 days. During liquid culture, NO3(-)
      and NH4(+) in the medium were gradually absorbed and utilized by hairy roots.
      NH4(+) -N of the medium was used up at day 15 of the culture, while NO3(-) in the
      medium was not used up, the content of which was 44.7% of the initial amount.
      Ca2+ of the medium was gradually absorbed and utilized during liquid culture and
      it was not used up at day 25, the content of which was still 43.5% of the initial
      amount. The results presented here had provided the possibilities on how to
      prepare optimum medium for large scale cultivation and production of solasodine
      from S. nigrum L. var. pauciflorum hairy roots.

PMID- 18630598
TI  - [Cloning and bioinformatic analyzing of transcription factor AP2/ERF-B3 subfamily
      genes from Brassica napus L. Huyou 15].
AB  - AP2/ERF is a large family of transcription factors in plant. Genes in the AP2/ERF
      family encode transcriptional regulators with a variety of functions involved in
      the developmental and physiological processes in plants. Two AP2/ERF family
      transcriptional regulators (BnaERFB3-1 and BnaERFB3-2) were isolated from B.
      napus by in silico cloning method using the conserved domain amino acid sequence
      of A. thaliana AP2/ERF-B3 subfamily as probe. Based on the sequences of BnaERFB3
      1 and BnaERFB3-2, we isolated the BnaERFB3-1-Hy15 gene and BnaERFB3-2-Hy15 gene
      from winter and spring type B. napus L. cv Huyou15 by RT-PCR and PCR using cDNA
      and DNA as template. DNA sequencing and analyzing indicated that there was only
      one amino acid residue difference between BnaERFB3-1 and BnaERFB3-1-Hy15,
      BnaERFB3-2 and BnaERFB3-2-Hy15, respectively. No intron localized on the two
      genes from Huyou15. Then, deduced amino acid sequence, composition, hydrophobicty
      and hydrophilicity, physical and chemical characterization, phylogenetic tree,
      conserved domain sequences, function domain, molecular modeling, and folding
      state were predicted and analyzed. BnaERFB3-1-Hy15 and BnaERFB3-2-Hy15 were
      hydrophilic protein. The two proteins and AtERF5 have similar three-dimension
      structure. The disordered residues of protein BnaERFB3-1-Hy15 and BnaERFB3-2-Hy15
      were higher than that of AtERF5. BnaERFB3-1 was mainly expressed in seed, while
      BnaERFB3-2 was mainly expressed in root. Moreover, those genes were successfully
      constructed into the recombinant plasmids of plant expression vector and yeast
      expression vector, which established a base for transformation of oilseed and
      studies of those genes function in abiotic stresses of B. napus.

PMID- 18630599
TI  - [Study on expression of mkp-1 and P-ERK in acutecontusive spinal cord injury
      rat's model].
AB  - To observe the expression of mitogen activated protein kinase phosphatase-1 (MKP
      1) and phosphorylation of extracellular signal-regulated kinases (P-ERK) of
      spinal cord in acute contusive spinal cord injury model, 20 Sprague Dawley rats
      were divided into two groups at random, Ten rats' spinal cord contusive injuries
      were produced by using modified Allen's method (using a weight-drop device) after
      the T10 spinous process and the corresponding vertebral lamina were removed as
      experimental group. The rest 10 rats received only T10 laminectomies and didn't
      injury the spinal cord as Sham-operated control group. The injury spinal cord was
      carried out respectively in two groups at 12h after injury. Pathological
      alterations were detected by H-E stain. The expression of MKP-1 and P-ERK were
      analyzed by immunohistochemistry and Western blot analysis. In Sham-operated
      control group, the micro structure of spinal cord was normal. The pathological
      alterations were very apparent in the damaged spinal cord area in the experiment
      group. We also found MKP-1 expression of spinal cord was decreased while P-ERK
      was increased in experimental group when compared with Sham-operated control
      group (P<0.01). The results suggested that acute contusive spinal cord injury
      down-regulated the expression of MKP-1 and up-regulated the PERK, which might
      play a role in the pathophysiological of spinal cord injury.

PMID- 18630600
TI  - [Transformation of Astragalus melilotoides Pall with AtNHX1 gene and the
      expression of salinity tolerance of transformants].
AB  - Using RT-PCR method, the open reading frame (ORF) of AtNHX1-cDNA, encoding the
      vacuolar Na+/H+ antiportor, was cloned from Arabidopsis thaliana seedlings
      pretreated with 100 mmol/L NaCl for 24h. This ORF was inserted between CaMV35S
      promoter, a Omega fragment of TMV RNA 5'UTR and NOS polyA terminator in the T-DNA
      region of a binary expression vector pNT (Fig1). The recombinant plasmid,
      designated as pNT-AtNHX1, was then transformed into Agrobacterium tumefaciens
      LBA4404. Mediated by this engineering Agrobacterium, the AtNHX1 gene was
      transferred into T0 generation transgenic plant strains of A. melilotoides and
      103 regenerated plants resistant to Kanamycin (Kan) were obtained. Some factors
      influencing the transformation efficiency, such as the concentration and
      infection duration of Agrobacterium, the concentration of Acetosyringone (AS),
      were optimized to establish a stable Agrobacterium mediated gene transformation
      protocol of A. melilotoides. PCR analysis, Southern blot and RT-PCR detection of
      some T0 transgenic plants showed that the AtNHX1 gene was evidently integrated
      into the genome of transgenic plants and couldl be transcripted properly. Under
      the same salt stress conditions, the detection of NaCl resistance revealed the
      difference between the wild-type calli and the transgenic calli that induced from
      the transgenic plants, i.e, the relative growth rates of the transgenic calli
      were remarkably higher than that of the wild-type calli. The K+ and Na+ contents
      and relative conductivity in the leaves of the transgenic plants and wild-type
      plants were estimated. It suggested that under the stress of different
      concentration of NaCl, K+/Na+ ratio in the transgenic plant cells were always
      higher than that in wild-type, however the situation of relative conductivity was
      on the opposite. From the facts above mentioned, the transformation of AtNHX1
      gene not only enhanced the salt tolerance of transgenic A. melilotoides, but also
      reduced the cell membrane damage induced by salinity.

PMID- 18630601
TI  - [Overexpression of the truncated fosb isoform (Delta2Deltafosb) increases nodus
      in CD1 primary osteoblastes].
AB  - The recombinant adenoviruses which can overexpress fosb and Delta2Deltafosb
      proteins were produced. Primary calvarial osteoblasts from new born CD1 mice were
      infected with those adenoviruses by different proportion of Ad-Delta2Deltafosb
      and induced by 5 mmol/L beta-glycerophosphate, 50 microg/ml ascorbic acid and 10
      nmol/L dexamethasone for 23 days and 29 days, respectively. The results by
      Alizarin Red Staining showed that the primary osteoblasts overexpressing
      Delta2Deltafosb protein formed more nodus than the control cells and the nodus in
      overexpressing Delta2Deltafosb protein osteoblasts were smaller than those in
      control cells on day 23. Differentiation of the primary osteoblasts
      overexpressing Delta2Deltafosb protein increased more than that of the control
      cells on day 29. It is an evidence for the reason that bone density of
      Delta2Deltafosb transgenic mice was markedly increased throughout the skeleton in
      new born and mature mice.

PMID- 18630602
TI  - In vitro culture and direct shoot regeneration from leaf explants of red-osier
      dogwood (Cornus stolonifera).

PMID- 18630603
TI  - [Expression and purification of the antimicrobial polypeptide by fusion with
      elastin-like polypeptide].
AB  - Elastin-like polypeptides (ELPs) are biological macromolecules designed on the
      elastic structure and composition. ELPs are thermally responsive polypeptides
      that undergo reversible inverse phase transition. Below their inverse transition
      temperature (Tt), ELPs are soluble in water, but when the temperature is raised
      above Tt, phase transition occurs, leading to aggregation of the polypeptide.
      Based on this property of ELPs, we investigated the ELPs as a fusion partner for
      the expression and purification of the antimicrobial polypeptide halocidin18 (18
      amino-acid subunit, Hal18). According to the amino acid sequence of hal18 and the
      bias for preferred codons of E. coli, the hal18 gene was synthesized by reverse
      PCR method and fused with the ELPs gene; the fusion gene was cloned into the
      prokaryotic expression vector pET23a to construct a recombinant expression vector
      pETH9E and then transformed into E. coli BL21 (DE3) to overexpress the
      recombinant fusion protein H9E. H9E was purified by inverse transition cycling
      (ITC) from the soluble fraction of the lysed E. coli. SDS-PAGE analysis results
      demonstrated that one-round of ITC purification could remove most of the
      contaminated proteins, and second-round could increase the purity of the fusion
      protein up to 95%. After cleavage and dialysis, Hal18 showed strong antimicrobial
      activities against E. coli and M. luteus which were used as representative gram
      negative and gram-positive bacteria, respectively. The results demonstrate that
      ELPs is an ideal fusion protein to express and purify the antimicrobial
      polypeptides.

PMID- 18630604
TI  - Identification of genes associated with early and late embryo development in
      rice.

PMID- 18630605
TI  - [Analytical prerequisites for reliable eGFR determination--editorial].

PMID- 18630606
TI  - [Notes on clinical interpretation of estimated glomerular filtration rate-
      editorial].

PMID- 18630607
TI  - [Hypoglycaemia--editorial].

PMID- 18630608
TI  - [CD classification from the point of view of experimental and clinical medicine-
      editorial].

PMID- 18630609
TI  - [Alcohol and cardiovascular risk--editorial].

PMID- 18630610
TI  - [Comments on binding Interdisciplinary European Guidelines on Surgery of Severe
      Obesity].

PMID- 18630611
TI  - [Pericardiocentesis afrer heart surgery--our experience].
AB  - Pericardial effusion after cardiac surgery is common, but only in a small part of
      patients it has progressive character and cardiac tamponade occurs. Accurate
      diagnosis and well-timed pericardiocentesis are necessary to effective management
      of this life threatening complication. The study aimed at presentation of our
      centre outcomes of echocardiographically-guided pericardiocentesis in patients
      after cardiac surgery. METHODS: Between December 2005 and November 2007, 2,232
      patients underwent open-heart surgery in our centre. At 48 (2.2%) of them
      pericardiocentesis for clinically significant pericardial effusion was performed.
      RESULTS: Pericardiocentesis was significantly more frequent after valve surgery
      (7.1%, p < 0.001), aortic root surgery (8.2%, p < 0.001) and surgical ablation of
      atrial fibrillation (6.6%, p < 0.001), i.e. in patients who had received
      postoperative anticoagulation therapy. Echo-guided pericardiocentesis was
      technically and therapeutically successful in 100% of cases and no complications
      were registered. The time elapsed between surgery and puncture was in range 6 to
      80 days (median, 13 days). The median volume initially aspirated was 450 ml
      (range, 50 to 1,550 ml). Forty five patients (93.8%) had extended catheter
      drainage with active suction, the median duration of the drainage was 1 day
      (range, 1 to 6 days), the mean volume of catheter drainage was 328 ml (median,
      145 ml; range, 20 to 2,950 ml). Four patients (8.3%) required repeated
      pericardiocenteses because of recurrence of significant pericadial effusion.
      Extended pericardial catheter drainage (after initial evacuation of the effusion)
      was associated with a significant reduction of recurrence of significant
      pericadial effusion and with lower probability of repeated pericardiocentesis. We
      can conclude, echo-guided pericardiocentesis was effective and safe method for
      primary treatment of postoperative pericardial effusions.

PMID- 18630612
TI  - [Higher incidence of thyropathy in patients with oesophageal achalasia. Genetic,
      autoimmune, regional or just a random association?].
AB  - INTRODUCTION: The etiology of esophageal achalasia is still largely unknown.
      Inflammatory response to an initial stimulus on the level of genetic and/or
      immune predisposition may be the underlying cause of the disease. The final
      result is progressive disappearance of ganglion cells in the myenteric plexus and
      motility disorder. Autoimmune thyropathy (AIT) is a typical disease involving
      genetic background and immune response disorder. PATIENTS AND METHODS: 44
      patients (of which 30 women and 14 men) with diagnosed esophageal achalasia and a
      control group of patients with esophageal reflux of corresponding age and sex
      were screened for thyroid disease. RESULTS: Thyroid disease was diagnosed in 15
      out of 44 patients with achalasia (34%). Thyropathy was detected in 11 women
      (37%) and 4 men (28%). AIT was detected in 10 patients, in 4 of whom with
      hypfunction, nontoxic cystic or nodular goitre was detected in 4 patients, 1
      patient was after strumectomy for benign node. Positive antithyroid antibody was
      newly detected in 4 patients with achalasia; subclinical hypothyreosis was found
      in one of them. There were two cases ofAIT with subclinical hypofunction and 1
      case of nontoxic goitre in the control group (7%). The difference was
      statistically significant (p < 0.01). CONCLUSION: The incidence of thyroid
      disease proved higher in patients with achalasia than in the controls. The rate
      of occurrence of thyroid disease exceeded significantly the occurrence in the
      population. The association of achalasia with prevailingly autoimmune thyropathy
      may corroborate the importance of autoimmunity in the etiopathogenesis of the
      disease.

PMID- 18630613
TI  - [Possibilities of evaluation of changes of glomerular filtration rate estimated
      on the basis of predicting formulas].
AB  - INTRODUCTION: Estimation of changes of glomerular filtration rate based on
      accurate measurement (GFR) and that based on predicting formulas (eGFR) could
      differ significantly. In this study we have tried to analyse the relationship
      between (eGFR)t2/(eGFR)t1 and (GFR)t2/(GFR)t1 (where t1 and t2 denote the time at
      the beginning and the end of the follow-up interval). METHODS: Renal clearance of
      inulin (Cin) was repeatedly examined in 32 patients suffering from chronic renal
      impairment (S(Cr) = 231 +/- 70 micromol/l). Estimated GFR (eGFR) was calculated
      on the basis of Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault
      (CG) equations. RESULTS: A significant relationship between (MDRD)t2/(MDRD)t1 and
      (Cin)t2/(Cin)t1 (r = 0.544, p = 0.0028, R2 = 0.295) as well as between
      (CG)t2/(CG)t1 and (Cin)t2/(CG)t1 (r = 0.556, p = 0.0026, R2 = 0.309) was found.
      Average difference between (MDRD)t2/(MDRD)t1-(Cin)t2 /(Cin)t1 was 0.017 +/- 0.17
      and that of (CG)t2 /(CG)t1-(Cin)t2/ (Cin)t1 was 0.024 +/- 0,18. Within +/- 0.20
      of the difference (eGFR)t2/(eGFR)t1-(Cin)t2 /(Cin)t1 59 % values were found and
      within +/- 0.30 of this difference 75% values were recorded. Highly significant
      relationship was found between (MDRD)t2/(MDRD)t1 and (CG)t2/(CG)t1 (r = 0.991; p
      = 0.0001; R2 = 0.983). CONCLUSION: Considering these preliminary findings,
      predicting formulas are not sensitive sufficiently to by able to detect GFR
      changes lower than 30% of initial value.

PMID- 18630614
TI  - [Traditional risk factors of atherosclerosis in patients with obstructive sleep
      apnoe-hypopnoe syndrome].
AB  - Cardiovascular morbidity and mortality of patients with obstructive sleep apnoe
      hypopnoe syndrome (OSAHS) is higher than in matched population. The aim of the
      study was to analyse, whether high prevalence of risk factors of atherosclerosis
      in patients with OSAHS can explaine their higher cardiovascular morbidity.
      METHODS: 2 groups of 33 males with moderate OSAHS and 16 males without OSAHS were
      subdivided into subgroups of apparently healthy subjects, hypertonics and
      patients with coronary artery disease. We compared the presence of traditional
      risk factors of atherosclerosis (age, hyperlipoproteinaemia, diabetes mellitus,
      arterial hypertension, obesity, smoking habit, obesity, family history),
      compensation of metabolic risk factors, morphometry of the heart, haemodynamic
      parameters, markers of atherosclerosis, microalbuminuria and some respiratory
      parameters. RESULTS: Patients with/without OSAHS had a comparable risk profile at
      all grades of cardiovascular pathology, they differed only in respiratory
      parameters (characteristic for OSAHS). Moreover, OSAHS patients without
      cardiovascular diseases vs. matched non OSAHS subjects had higher thickness of
      posterior wall of the left ventricule (9.73 +/- 1.17 vs 8.29 +/- 1.38 mm, p <
      0.04), intima-media thickness of carotid artery (0.83 +/- 0.14 vs 0.63 +/- 0.08
      mm, p < 0.001) and OSAHS patients with hypertension vs non OSAHS hypertonics
      presented higher dimension of right ventricule (28.4 +/- 2.7 vs 26.25 +/- 0.96
      mm, p < 0.02), and left ventricule (47.6 +/- 3.3 vs 43.75 +/- 0.96 mm, p < 0.01).
      CONCLUSION: Patients with OSAHS had severe atherosclerosis and worse
      morphological alteration of the heart compared to subjects without OSAHS.
      According to comparable presence and possibility of sufficient control of risk
      factors, OSAHS can be considered to be a risk factor for cardiovascular diseases.
      However, this statement has to be further confirmed in prospective studies.

PMID- 18630615
TI  - [Results of the PREDICTIVE project in the Czech Republic].
AB  - INTRODUCTION: The PREDICTIVE project was an international multicentric, open
      observation study evaluating the safety and efficiency of insulin detemir in
      clinical practice. 1,695 type 1 or 2 diabetes mellitus (DM) patients were
      enrolled in the study in the Czech Republic. The patients were treated by insulin
      detemir for the period of 26 weeks in accordance with the standard scheme
      implemented by the treating doctor. The primary objective of the study was to
      monitor the incidence of serious adverse events including severe hypoglycaemias.
      The secondary objective of the study (the number of adverse events, the incidence
      of all and nocturnal hypoglycaemic episodes, the variability of fasting
      glycaemia, the change in HbA1c at the end of the study, the change in the
      patients' weight) focused on the safety and efficiency of diabetes treatment.
      RESULTS: Insulin detemir therapy resulted in a statistically significant decrease
      in all nocturnal episodes (from 26.8 to 10.4 episodes/patient/year in type 1 DM;
      from 9.2 to 2.6 in persons with type 2 DM), in severe nocturnal episodes (from
      2.5 to 0.1 episode/patient/year in type 1 DM, and from 0.6 to 0 in type 2 DM),
      and also in hypoglycaemic nocturnal episodes (from 7.2 to 1.8
      episode/patient/year in type 1 DM and from 1.7 to 0.3 in type 2 DM) as compared
      with the period preceding the therapy. In addition, detemir therapy resulted in a
      statistically significant improvement of diabetes compensation characterised by a
      decrease in the average HbAlc from 7.6% to 6.7% in type 1 DM patients, and from
      7.9% to 7.0% in type 2 DM patients. Average fasting glycaemia recorded a
      significant decrease by 2.4 mmol/l in type 1 DM patients, and by 2.3 mmol/l in
      type 2 DM patients. Also the variability of fasting glycaemia recorded a
      significant decrease at the end of the study in both patient groups. No major
      change in weight was recorded in the course of the study in persons with type 1
      DM, while a significant decrease in weight was recorded for type 2 DM patients.
      CONCLUSION: The results of the study PREDICTIVE confirmed the data from
      randomised studies on the safety and efficiency of insulin detemir treatment in
      the conditions of standard clinical practice in the Czech Republic.

PMID- 18630616
TI  - [Pathogenesis of insulin resistance in different endocrinopathies].
AB  - Visceral obesity, insulin resistance and increased cardiovascular morbidity and
      mortality are strongly related. Development of visceral obesity and regulation of
      body fat distribution in general are influenced by many factors. This article is
      a summary of current knowledge about pathogenesis of insulin resistance in
      different endocrinopathies, particularly in the Cushing's syndrome and
      acromegaly, as they are both connected with the pathological conditions mentioned
      above.

PMID- 18630617
TI  - [Exenatid and its position as antidiabetic drug in the treatment of type 2
      diabetes mellitus].
AB  - 'Incretin effect' refers to increased insulin response to oral glucose as
      compared to i.v. glucose response. Incretin mimetics are a new class of
      antidiabetic drugs lowering hyperglycaemia. Incretin mimetics mimic the natural
      human hormones called 'incretins' with blood glucose regulating action. Exenatide
      is a synthetic analogue GLP-1 which is resistant to enzymatic degradation by DPP
      IV. Subcutaneously administered exenatide stimulates insulin secretion,
      suppresses glucagon secretion, slows down stomach evacuation and reduces the
      weight. Its administration is safe and the most frequent side effect is mild
      nausea.

PMID- 18630618
TI  - [Hypoglycaemia].
AB  - Hypoglycaemia is a serious, frequent and recurrent complication of treatment of
      diabetes mellitus which may become a direct danger to the patient's life. In
      clinical practice, it is best defined descriptively as Whipple's triad involving
      the presence of typical clinical symptoms of hypoglycaemia, low plasma glucose
      concentration and the disappearance of symptoms of hypoglycaemia after the
      administration of glucose. The overview article focuses, in more detail, on the
      issues of definition of hypoglycaemia based on the optimal threshold value
      ofglycaemia, classification ofhypoglycaemia based on its causes, rate of
      occurrence and factors provoking hypoglycaemia in patients with type 1 and 2
      diabetes mellitus, as well as modern diagnosis and treatment of hypoglycaemic
      states.

PMID- 18630619
TI  - [The importance of determining the viability of the myocardium prior to
      revascularisation in patients with ischaemic cardiomyopathy and left ventricular
      systolic dysfunction].
AB  - Chronic heart failure is a worldwide clinical syndrome with substantial socio
      economical impact. The aim of this overview is the summary of contemporary
      knowledge in epidemiology, elementary pathophysiological implications and some
      possibilities of treatment of ischemic cardiomyopathy, which represents the most
      frequent cause of heart failure in developed countries. Emphasis is on the right
      indication for myocardial revascularization as a causal option of therapy of
      ischemic cardiomyopathy, timing and risk of revascularization and especially on
      importance of assessment of viability of myocardium using presently available
      imaging methods.

PMID- 18630620
TI  - [Human leukocyte differentiation antigens and CD classification].
AB  - The autor summarizes the information about human leukocyte antigens. Expression
      of membrane markers is included in accordance with CD (Cluster of
      Differentiation) classification. The CD molecules are used ubiquitously in human
      medical research, immunodiagnosis and treatment and also CD profiles are intended
      to be used by biologists, pathologists and clinicians generally. Profiles nearly
      400 known leukocyte cell surface molecules are summarized in CD system (CD1
      CD350). Most CD molecules are integral membrane proteins that have one or more
      pass through the plasma cell membranes. Knowing which regions of a protein are
      intracellular or extracellular is important in the selection of peptides for
      immunization, for the expression of domains of the protein, and to understand the
      interaction of the protein with other proteins. CD markers are great targets for
      diagnostic and research of different types of diseases as a potential treatment
      for a variety of tumors.

PMID- 18630621
TI  - [ECG changes in alcoholic intoxication].
AB  - Patients with acute alcohol intoxication often present with pathological
      electrocardiographic (ECG) changes. The changes are more frequent and
      prognostically more significant in chronic alcoholics, in patients with ischaemic
      heart disease (IHD), in alcohol cardiomyopathy or another organic heart disease,
      but they can also occur in young and healthy individuals. The typical ECG changes
      in inebriety are disturbances of heart rate having the nature of electric impulse
      generation disorder or of impulse conduction pathology. In persons without
      clinical evidence of heart disease, they are classified as 'holiday heart
      syndrome'. The most frequent tachyarrhythmia is atrial fibrillation; less
      frequent but prognostically much more significant is torsades de pointes (TdP)
      polymorphous ventricular tachycardia. Among bradyarrhythmias, the most
      significant is alcohol-induced sinus bradycardia which may be manifested by
      recurrent syncope. The higher the blood alcohol concentration, the higher the
      occurrence of a significant extension of ECG intervals with possible
      manifestation of latent conduction disturbance or even sudden cardiac death.
      Apart from heart rate disturbances, ECG picture very often shows non-specific
      repolarisation changes. Ischaemia, which is mostly asymptomatic in the form of
      silent myocardial ischaemia, is worsened in alcohol-intoxicated IHD patients. The
      resulting ECG may be to a large extent influenced by states which often associate
      with inebriety, such as hypothermia, hypoglycaemia or electrolyte imbalance. ECG
      changes similar to those due to acute alcohol intoxication are also present in
      acute abstinence syndrome, especially in delirium tremens. There is convincing
      evidence that not only chronic alcoholism, but also single episodes of excessive
      alcohol consumption are associated with increased cardiovascular mortality.

PMID- 18630622
TI  - [Preparation of patients with haemostasis disorder for dental surgery].
AB  - The most of patients need dental care during their time of life. It can be
      situation to detect bleeding disorder in patients who have been suggested
      apparently healthy to this time. In patients with known bleeding tendency it can
      be situation in which good interdisciplinary coordination is necessary. In the
      most cases patients with anticoagulation treatment are involved between those
      with haemostasis problems. Nevertheless, they do not need therapy interruption in
      the most of cases, only the knowing actual therapeutic level of INR and
      appropriate stomatologist's erudition. Another situation is in patients with
      severe haemostatic bleeding disorder. They don't need only special procedure in
      dental extractions but also lifelong dental care. One can establish patients, in
      whom it is not possible only outpatient treatment but in whom a few days
      hospitalization is necessary. Above all they are patients with haemophilia and
      inhibitor, those with multiple or surgery extractions and persons with multiple
      haemostasis impairment.

PMID- 18630623
TI  - [Inter-disciplinary European guidelines on surgery of severe obesity].

PMID- 18630624
TI  - [Lyme carditis--rare cause of dilated cardiomyopathy and rhythm disturbances].
AB  - Case report of young woman presents involvement of dilated cardiomyopathy and
      rhythm disturbances in 18 months after infection of tick, with direct assessment
      of spirochetes in myocardial tissue. Cardial decompensation occured after asthma
      exacerbation, complicated by bronchopneumonia. Rhythm disturbances and heart
      failure gradually subside after parenteral antibiotic treatment and peroral
      treatment of heart failure. Nevertheless there is a long-lasting persistence of
      dilated cardiomyopathy with significant systolic dysfunction, which is supposedly
      last consequence of Borrelia infection. Resynchronic therapy combinated with
      cardioverter-defibrilator primary considering was postponed for improvement
      clinical condition and myocardial electric stability. There is demonstrating
      complicated serologic diagnostics of Lyme disease in discussion. Lyme carditis
      would be part of differential diagnosis in rhythm disturbances and cardiomyopathy
      of unknown etiology, including serious or fatal events.

PMID- 18630625
TI  - [Haemocoagulation and renal insufficiency, haemocoagulation and type 2 diabetes
      mellitus].
AB  - Diabetes mellitus is a frequent cause of renal insufficiency. Renal insufficiency
      is associated with both haemorrhagic manifestations primarily caused by platelet
      functional disorders, and states of hypercoagulation resulting from significant
      hyperfibrinogenemia. Fibrinolysis is either increased or, often, decreased.
      Changes in haemostasis in renal insufficiency have been dealt with by many
      authors in relevant literature. However, the final stage of renal insufficiency
      is rather dominated by haemorrhagic diathesis. It is manifested by skin
      haemorrhage, mucosal manifestations, but also by retroperitoneal and cerebral
      haemorrhage. The main cause of a haemorrhagic condition is platelet dysfunction
      combined with anticoagulation and antiplatelet therapy which is used in dialysis.
      Platelet function disorders are provoked by acquired thrombocytopaenia and result
      in a disorder in the interaction between the blood vessel wall and the platelet.
      Dialysis suppresses platelet abnormalities only temporarily by suppressing uremic
      toxins provoking platelet disorders. On the other hand, dialysis may cause
      prothrombotic activity. Changes in haemostasis in type 2 diabetes mellitus form
      part of the insulin resistance syndrome and induce prothrombotic condition due to
      decreased fibrinolysis.

PMID- 18630626
TI  - [Urologic surgery in diabetes].
AB  - INTRODUCTION: The diabetes mellitus is risk factor for urologic surgery. The best
      prevention of complications is excellent compensation of diabetes, appropriated
      management of anesthesia and good post surgery care. The diabetes is etiologic
      risk factor many urologic diseases including malignant. UROLOGIC SURGERY: The
      diabetes is intensively evaluated in uro-oncology and it seems that renal cell
      carcinoma and bladder cancer incidence is higher in diabetic patients. The link
      between prostate cancer and diabetes is not clear, yet. The behavior of this
      cancer is more aggressive and it has worse prognosis. The diabetes is risk
      etiologic factor for urolithiasis and benign prostatic hyperplasia.
      Immunodeficiency combined with diabetes has negative impact for urinary tract
      infection including most serious as emphysematous pyelonephritis or Fournier
      gangrene external genitalia. CONCLUSION: The accurate compensation of the
      diabetes is basic condition good results of urologic surgery in diabetics. The
      diabetes mellitus and obesity will be evaluated as risk factors many diseases of
      kidneys and whole urologic apparatus especially malignant.

PMID- 18630627
TI  - [Tumours of kidneys, urinary bladder and prostate in obesity and diabetes].
AB  - Relations of obesity and type 2 diabetes to urinary tract cancer were described.
      Occurrence of kidney cancer is more often in both obesity and type 2 diabetes.
      Bladder cancer has no relation to obesity but is more common in type 2 diabetic
      patients. Inverted relations were found in prostatic cancer. This disease is more
      common in obese patents but less common in type 2 diabetes. Diabetics are partly
      protected to this disease. Physical activity decreases the risk of kidney and
      bladder cancer but has no relation to bladder cancer. Urinary tract cancers have
      no relation to type 1 diabetes. We have found 3.9 time higher risk of kidney
      cancer in Czech diabetic patients.

PMID- 18630628
TI  - [Bariatric surgery and the kidneys].
AB  - Overweight and obesity are connected with increased risk of obesity related co
      morbidities, such as T2DM, hypertension, cardiovascular diseases, dyslipidaemia
      and others, as well as in higher risk of some malignant diseases. In obese
      population there is 2.5-3.3 fold increased risk of renal cell carcinoma in
      comparison with non-obese population of similar age. It has been proven in many
      studies that for severely obese patients there is no other more effective
      treatment of their obesity and co-morbidities than bariatric. Bariatric surgery
      decreases mortality risks, treat existing, obesity related co-morbidities, and
      can act as prevention of onset of new obesity related co-morbidities. Moreover at
      the end bariatric surgery lowers economic burden of health care systems.
      Nowadays, bariatric surgery is considered to be standard treatment option and
      pathway in complex management of morbidly obese patients.

PMID- 18630629
TI  - [The use of organ specific substrates in kidney disease in a diabetic patient].
AB  - Diabetic nephropathy is one of the principal causes of chronic renal failure. The
      disease prevailingly develops in men. The incidence of diabetic nephropathy
      doubled from 1991 to 2001. There are different traditional dietary guidelines for
      the different states of diabetic nephropathy, as well as pharmacotherapy options,
      and, last but not least, also modern ways of application of nutritional
      pharmacology. Organ specific nutritional substrates - amino acids,
      polyunsaturated fatty acids and other components of nutrition with
      pharmacological effects have become indispensable in modern care for diabetic
      patients.

PMID- 18630630
TI  - [Nutrition for the diabetic patient with kidney disease].
AB  - Malnutrition is a major problem in chronically ill patients. The combination of
      diabetes and renal insufficiency increases the risk of malnutrition, also due to
      dietary interventions associated with the two diseases. Resulting malnutrition
      intensifies inflammatory activity and further compromises nutrition intake. This
      results in a vicious circle which significantly reduces the quality of life of
      the affected patients and increases their mortality. Proper nutritional care for
      such patients is an integral part of their treatment.

PMID- 18630631
TI  - [Mucosal immunity with emphasis on urinary tract immunity and diabetes].
AB  - Protective immune response in urinary tract is frequently impaired in patients
      with diabetes. Immunity in this mucosal compartment displays unique
      characteristics; e.g. absence of physiological microflora and lack of mucus.
      Pathogens are identified by the PRR receptors expressed on both epithelial and
      immune cells. Inflammatory response characterised by the acumulation
      ofgranulocytes is followed. Both protective and harm characteristics of
      inflammatory response are inseparable linked and delineated by gene polymorphisms
      in PRR receptors.

PMID- 18630633
TI  - [Erectile dysfunction, its relation to diabetes and its management in 2007].
AB  - Medical know-how today allows for thorough examination and assessment of erection
      disorders. The doctor carrying out the examination focuses on detecting the
      underlying disease of which erectile dysfunction (ED) is a marker and the nature
      of which may be much more significant than ED itself. However, the detecting and
      treating of the disease associated with ED usually does not resolve the problem.
      The management of ED as such is based on the options which there are for the
      patient in line with the principle of choosing a less invasive therapy as the
      preferred option. Diabetes (DM) is one of the metabolic syndrome (MS) diseases
      which have a high rate of associated ED.

PMID- 18630632
TI  - [Visceral diabetic neuropathy of the urogenital tract].
AB  - The article deals with issues of diabetic autonomous neuropathy (DAN) in the
      urogenital tract (UGT), and brings attention to the ethiopathogenesis of diabetic
      polyneuropathy. It provides a synopsis of autonomous neuropathy and deals, in
      more detail, with its manifestations in the UGT. The different symptoms of the
      disorder are addressed, the need for timely diagnosis is pointed out as the
      prerequisite for a successful therapy, and the necessity for interdisciplinary
      cooperation in dealing with this health issue is exposed.

PMID- 18630634
TI  - [Epidemiology of diabetic nephropathy].
AB  - The epidemiology of diabetic nephropathy (DN) should be approached from two
      angles: a) incidence of diabetic nephropathy in patients with diabetes, and b)
      epidemiology of chronic renal failure (CHRF) in diabetic patients. According to
      data from different sources, DN affects, in all its stages, about one third of
      patients irrespective of the type of diabetes they suffer from, with the peak
      rate of incidence after 15 years of duration of the illness. It is estimated that
      the rate of DN prevalence is 4-8% of patients monitored in diabetes centres. In
      addition, a significant portion of diabetics, especially the type 2 diabetic
      patients, are affected by the non-diabetic type nephropathy of primarily
      atherosclerotic etiology. Currently, DN is the principal cause of CHRF in
      advanced industrial countries (Western Europe, USA,Japan). A similar trend has
      been recorded in the Czech Republic which has one of the highest incidences of DN
      among the former Eastern Block countries. Most affected patients are type 2
      diabetes patients. The cause of the above increase is the growing prevalence and
      incidence of type 2 diabetes, and, primarily, better care for type 2 diabetes
      patients who live long enough to develop severe macro and microvascular
      complications including DN. The principal factors influencing the risk of a
      diabetic patient developing DN are long-term monitoring ofglycaemia, control of
      hypertension, genetic (ethnic) factors, age and sex. Metabolic control has an
      effect on the risk of diabetic nephropathy developing in type 1 and 2 diabetes,
      yet it is blood pressure control which is critical for the progression of chronic
      renal insufficiency in DN patients. In view of the high number of diabetic
      patients with CHRF which, in addition, associates with their high polymorbidity
      and extensive demands put on medical and nursing care which is not directly
      associated with CHRF therapy, we have to do with a serious medical and economic
      problem.

PMID- 18630635
TI  - [Examination of the kidneys in a diabetic patient].
AB  - Diabetic nephropathy is the most frequent cause of terminal renal failure in the
      Czech Republic today. Diabetic patients should be screened for diabetic kidney
      disease on an annual basis, starting 5 years after diabetes was diagnosed in type
      1 diabetes patients and immediately after diagnosis in type 2 diabetes patients.
      The screening includes determining the albumin/creatinine ratio from a urine
      sample, and of serum creatinine, and the calculation ofglomerular filtration
      rate. In patients in whom microalbuminuria and/or proteinuria were found,
      measures should be taken to reduce cardiovascular risk and to slow down the
      progression of renal disease. In diabetic patients with abnormal urine test
      results detailed nephrology examination is necessary to exclude other renal
      diseases than diabetic nephropathy, especially chronic glomerulonephritis and
      ischaemic nephropathy.

PMID- 18630636
TI  - [Diabetes mellitus, hypertension and kidney].
AB  - The correlations co-exist among diabetes mellitus, hypertension and the kidney.
      Renal injury will develop in 35% type 1 and type 2 diabetes mellitus patients.
      Diabetic nephropathy is the key factor for the occurence of hypertension in type
      1 diabetes mellitus. In case of type 2 diabetes mellitus with prevalent essencial
      hypertension the diabetic nephropathy is supporting factor for the development of
      hypertension. Untreated or inadequately treated hypertension accelerates the
      progression of diabetic renal impairment. The presence of diabetes mellitus as
      well as hypertension or proteinuria is significant cardiovascular risk factor.
      The goal of treatment with angiotensin converting enzyme inhibitors or AT1
      receptor of angiotensin II blockers is both slowing-down of renal injury
      progression and reduction in risk of cardiovascular complications.

PMID- 18630637
TI  - [System renin-aldosterone in fat tissue and other organ and tissues].
AB  - Important mechanism of pathogenesis of hypertension in obesity is renin
      aldosterone system in adipose tissue. Adrenal cells can be also stimulated to
      aldosterone secretion by local adrenal fat cells and also by other factors from
      fat tissue (lipids, endocrine disruptors). Local system renin-aldosteron is
      active also in other tissues and organs in obesity related hypertension. Feed
      back is closed by recently investigated fact that aldosteron hypersecretion can
      cause metabolic syndrome. Between systemic approach to obesity a new phenomenon
      of organ obesity is coming - adipokines from local fat cells can influence organ
      and tissue function e.g. in essential hypertension.

PMID- 18630638
TI  - [Diabetes, dyslipidaemia and kidney diseases].
AB  - Dyslipidemia (DLP) is the most significant risk factor for cardiovascular
      diseases (CVD). Similarly, the relevance of diabetes mellitus (DM) as a CVD risk
      indicator is so high that it is attributed the same significance as the secondary
      prevention ofCVD in different systems of global cardiovascular risk assessment.
      Most recently, also kidney disorders have been increasingly referred to as a risk
      factor for the manifestation of CVD. According to some guidelines, patients with
      kidney disorders are at the same risk as the patients with manifest IHD (or
      another manifestation of atherosclerosis), and patients with DM. This paper does
      not pretend to resolve the complex relationship between DLP, DM and nephropathy.
      Its sole objective is to bring attention to the fact that it is a relevant and
      significant issue which is gradually becoming a central point of attention. The
      first part of the article deals primarily with diabetic DLP and the different
      options for its management. The second part deals with the role of DLP in kidney
      disorders, the risk it represents and the options for its management, as well as
      with the results of the first intervention studies. The studies focused on the
      effect of hypolipidemic therapy on CV risk of patients on the one hand and, on
      the other hand, on the way hypolipidemic drugs contribute to the improvement or
      sustaining of renal functions, or on their influence on renal disease markers.

PMID- 18630639
TI  - [Specific issues of dialysed diabetics in outpatient practice].
AB  - Approximately 40% of patients on dialysis have diabetes mellitus (DM). The basic
      characteristic of those patients are numerous associated organ complications,
      especially heart and artery diseases. These and other associated complications in
      dialysed diabetic patients have a modified pathogenetic and clinical picture and
      contribute to their poorer prognosis. Anaemia, immunodeficiency as well as
      malnutrition are manifested earlier and in a more significant manner. Dialysis
      therapy has the same rules for diabetic and non-diabetic patients. Tolerance to
      ultrafiltration is lower and haemodynamic instability is easier to provoke in
      diabetics than in non-diabetic patients. The use of a dialysis solution is
      beneficial from the point of view of glucose concentration balance. Insulin doses
      are lower as a result of extended insulin half-time. There is also a degree of
      insulin resistance, but it can be managed to a great extent by adequate dialysis.
      There are no fixed guidelines for insulin dosing; the doses roughly amount to
      half of the doses in patients with normal renal function. The assessment of
      diabetes compensation is based on glycated haemoglobin, and glycated albumin is
      also recommended in certain cases. Deciding on the therapy (oral antidiabetic
      drugs vs. insulin therapy or a combination of both) is based on diabetic care
      standards; cooperation between the diabetologist and the dialysis doctor is
      desirable. Customized, specifically designed and targeted intervention in
      diabetic patients may slow down the progression of diabetic vascular changes,
      improve diabetes compensation and the patients' quality of life.

PMID- 18630640
TI  - [Specific aspects of peritoneal dialysis in diabetic patients].
AB  - Together with hemodialysis and renal transplantation, peritoneal dialysis is an
      established method of renal replacement therapy. While evolving in parallel with
      hemodialysis worldwide, it was not until 1990 that peritoneal dialysis, as we
      know it today, was introduced to this country when high-quality disposables also
      became available. In the early 1990s, after adequately increasing the throughput
      of our dialysis and transplant centers, renal replacement therapy became
      available to all patients requiring it, that is, also to those with diabetes and
      other patients with comorbidities in this country. The mortality rates of
      dialysis-dependent patients with diabetes and chronic renal failure are
      significantly higher compared with those of dialysis patients without diabetes.
      This holds true both for hemodialysis and peritoneal dialysis. The survival rates
      of dialysis patients (with and without diabetes) over the first years of dialysis
      treatment are higher for those on peritoneal dialysis compared with hemodialysis,
      presumably because residual renal function is maintained longer with peritoneal
      dialysis. Peritoneal dialysis in patients with diabetes is usually associated
      with a higher incidence of peritonitis, but not its complications. This is not
      the case in our unit where the incidence of peritonitis does not differ
      significantly between patients with diabetes (1 : 38.9 months) and those without
      it (1 : 51.4 months). However, peritonitis incidence in our center is kept at
      levels much lower than accepted by the European guidelines (1 : 24) and those
      developed by the International Society of Peritoneal Dialysis (1 : 18), and than
      is usual in current clinical practice. Peritoneal dialysis patients and, in
      particular, those with diabetes, are likely to benefit from the use of modern
      peritoneal dialysis solutions containing the glucose polymer icodextrin or amino
      acids as the osmotic agent instead of glucose, or dialysis solutions with a
      reduced content of glucose degradation products. Such solutions have been shown
      to feature improved biocompatibility parameters and lower systemic metabolic
      load. Some observational non-randomized trials have reported improved survival
      and a lower incidence of peritonitis in patients both with and without diabetes
      treated with these modern dialysis solutions. Randomized trials are warranted to
      confirm these findings.

PMID- 18630641
TI  - [Education of diabetic patients with chronic kidney disease and after
      transplantation].
AB  - Despite recent advances in the management of diabetes, diabetic nephropathy is
      the most frequent cause ofend-stage renal disease. Even when diabetic nephropathy
      is established, patient's care should be optimized to delay progression of
      nephropathy or other diabetic complications. Evidence exists for the
      effectiveness of diet intervention, blood pressure and diabetes control and
      treatment of metabolic syndrome. We emphasize the need for closer co-operation
      not only between diabetologists, primary care physicians and nephrologists, but
      with educated diabetic patients, too. At referral to nephrologist, many patients'
      care is suboptimal and referral is too late. The most important education
      information for patients is to stick to diet and keep adequate blood pressure and
      diabetes control with self-monitoring. Effectiveness of each of these
      recommendations is critically assessed. Patients after kidney or combined kidney
      and pancreas transplantation have to be educated mainly in symptoms of rejection
      and diabetic foot care. They are recommended to take regularly the prescribed
      medicines, to distinguish the adverse events of immunosuppression and keep all
      doctor's appointments.

PMID- 18630642
TI  - [Metformin and kidneys].
AB  - Metformin is currently recommended as the first-line drug for type 2 diabetic
      patients once the disease has been diagnosed. In addition to antihyperglycaemic
      effect, it has other effects which have a positive effect on cardiovascular risk.
      The greatest risk of metformin treatment is lactate acidosis, but its incidence
      is very low if the contraindications are observed. In spite of the fact that not
      all contraindications are observed in practice, the incidence of lactate acidosis
      demonstrably provoked by metformin does not grow. In spite of ongoing discussion
      on the subject, contraindications still include all states involving the risk of
      lactacidosis including renal insufficiency.

PMID- 18630643
TI  - Cognitive performance and morning levels of salivary cortisol and alpha-amylase
      in children reporting high vs. low daily stress perception.
AB  - The aim of the present study was to assess the effects of daily stress perception
      on cognitive performance and morning basal salivary cortisol and alpha-amylase
      levels in healthy children aged 9-12. Participants were classified by whether
      they had low daily perceived stress (LPS, n = 27) or a high daily perceived
      stress (HPS, n = 26) using the Children Daily Stress Inventory (CDSI). Salivary
      cortisol and alpha-amylase were measured at awakening and 30 minutes later.
      Cognitive performance was assessed using the Cognitive Drug Research assessment
      system. The HPS group exhibited significantly poorer scores on speed of memory (p
      < .05) and continuity of attention (p < .05) relative to the LPS group. The HPS
      group also showed significantly lower morning cortisol levels at awakening and at
      +30 minutes measures in comparison with the LPS group (p < .05), and mean morning
      cortisol levels were negatively correlated with speed of memory (p < .05) in the
      53 participants. No significant differences were observed between both groups in
      alpha-amylase levels. These findings suggest that daily perceived stress in
      children may impoverish cognitive performance via its modulating effects on the
      HPA axis activity.

PMID- 18630644
TI  - Psychophysiological, behavioral, and cognitive indices of the emotional response:
      a factor-analytic study.
AB  - Previous research on the components of the emotional response employing factor
      analytic studies has yielded a two-factor structure (Lang, Greenwald, Bradley, &
      Hamm, 1993; Cuthbert, Schupp, Bradley, Birbaumer, & Lang, 2000). However, the
      startle blink reflex, a widely employed measure of the emotional response, has
      not been considered to date. We decided to include two parameters of the startle
      reflex (magnitude and latency) in order to explore further how this response fits
      into the two-factor model of emotion. We recorded the acoustic startle blink
      response, skin conductance response, heart rate, free viewing time, and picture
      valence and arousal ratings of 45 subjects while viewing 54 pictures from the
      International Affective Picture System (IAPS; 18 unpleasant, 18 neutral, and 18
      pleasant). Factorizations of all measures gave a two-factor solution (valence and
      arousal) that accounted for 70% of the variance. Although some measurements,
      including heart rate change, did not behave as predicted, our results reinforce
      the two-dimension model of the emotion, and show that startle fits into the
      model.

PMID- 18630645
TI  - Children like dense neighborhoods: Orthographic neighborhood density effects in
      novel readers.
AB  - Previous evidence with English beginning readers suggests that some orthographic
      effects, such as the orthographic neighborhood density effects, could be stronger
      for children than for adults. Particularly, children respond more accurately to
      words with many orthographic neighbors than to words with few neighbors. The
      magnitude of the effects for children is much higher than for adults, and some
      researchers have proposed that these effects could be progressively modulated
      according to reading expertise. The present paper explores in depth how children
      from 1st to 6th grade perform a lexical decision with words that are from dense
      or sparse orthographic neighborhoods, attending not only to accuracy measures,
      but also to response latencies, through a computer-controlled task. Our results
      reveal that children (like adults) show clear neighborhood density effects, and
      that these effects do not seem to depend on reading expertise. Contrarily to
      previous claims, the present work shows that orthographic neighborhood effects
      are not progressively modulated by reading skill. Further, these data strongly
      support the idea of a general language-independent preference for using the
      lexical route instead of grapheme-to-phoneme conversions, even in beginning
      readers. The implications of these results for developmental models in reading
      and for models in visual word recognition and orthographic encoding are
      discussed.

PMID- 18630646
TI  - Initial models in conditionals: evidence from priming.
AB  - We examined the comprehension of different types of conditionals. We measured the
      reading time of sentences primed by different types of conditionals (Experiments
      1 and 2). We found that the participants read not-p and not-q faster when it was
      primed by the conditional form p if q and they were slower to read p and q when
      it was primed by the conditional form p only if q. This effect disappeared in the
      second experiment, where the order of the elements was reversed (q and p and not
      q and not-p). These results suggest that the conditional form p if q elicits an
      initial representation "from p to q" with two possibilities, while the
      conditional form p only if q elicits a reverse representation with only one
      possibility. The third experiment showed that there were effects of the order
      only for the conditional if p then q, which confirms the reverse representation
      hypothesis. We discuss the implications of these results for different theories
      of conditional comprehension.

PMID- 18630647
TI  - Evidence for linguistic deficit in nonlexical processing in reading. A study of a
      Spanish-speaking patient.
AB  - Previous studies have shown that in the so-called opaque languages (those in
      which spelling does not correspond to pronunciation), there are relatively
      independent routes for lexical and nonlexical processing, that is, for words and
      nonwords, both in spoken and in written language. On the other hand, in the so
      called transparent languages (those in which pronunciation corresponds to written
      forms), empirical evidence is scarcer. In this study of a neurological patient
      (parieto-temporal lesion), speaker of a transparent language (Spanish) showing a
      specific deficit in nonlexical reading processing, linguistic analysis for words
      was relatively preserved. This finding suggests the use of various routes in the
      processing of transparent languages.

PMID- 18630648
TI  - Women's access to managerial positions: an experimental study of leadership
      styles and gender.
AB  - This study attempts to test one of the explanations of the scarce representation
      of women in managerial positions, specifically the one advanced by "role
      congruity theory of prejudice toward female leaders" (Eagly & Karau, 2002), which
      appeals to the fact that women get unfavorable evaluations if they adopt male
      stereotypical leadership styles. One-hundred and thirty-six undergraduate
      students participated in an experiment with a 2 (Male-stereotypical vs. Female
      stereotypical leadership style) x 2 (Male vs. Female leader) design. Dependent
      variables were leader's competence, efficacy, and evaluation in a series of
      traits. It was found that, regardless of sex, the leaders were considered more
      competent and efficient, and were evaluated more favorably, when they adopted
      stereotypically feminine leadership styles. Implications of these findings for
      women's underrepresentation as leaders in management top positions worldwide are
      discussed.

PMID- 18630649
TI  - Variations on an old theme: maternity for women with a very successful
      professional career.
AB  - In this study, relationships of middle-class women from Rio de Janeiro with their
      family and work are presented. A series of events during the 20th century have
      changed woman's identity, previously centered on the roles of mother and wife, so
      that, there are now other options for women. Carioca girls are currently educated
      to compete, seek greater professional growth, and value their independence.
      However, some social discourses still reinforce women's former role the in the
      family. The notion that the mother-child unit is basic, universal, and,
      psychologically, the most appropriate, both for the child's healthy development
      and the mother's wholeness, is still firmly rooted. Motherhood is therefore one
      of the most complex and problematic matters for modern Carioca woman. Fifteen
      women with successful professional careers, residents of the city of Rio de
      Janeiro, varying in age from 30 to 40, and with children from 6 months to 3 years
      of age, were interviewed. The interviews had an invisible structure, were
      recorded and transcribed. The discourse of the resultant texts was analyzed,
      using the categories I established. In this project, I focus on the results of
      the analysis of the category "View of Maternity" of the interviewed women.

PMID- 18630650
TI  - Neighborhood and community factors: effects on deviant behavior and social
      competence.
AB  - Socialization in a neighborhood and community at risk, defined in terms of
      violence, social alienation, school failure, and disruptive behavior, is a risk
      factor for the acquisition of antisocial and delinquent behavior. In order to
      test this hypothesis and examine the underlying mechanisms involved, 346
      participants, 155 high-risk and 191 low-risk, aged 11 to 13, that is, under the
      age of criminal responsibility as established by the Spanish Law 5/2000 were
      selected. The results reveal that high-risk youngsters had higher rates of
      antisocial behavior and lower levels of social skills (i.e., greater tendency to
      externalize attribution of responsibility, fewer conflict resolution strategies,
      lower self esteem, and a lower degrees of emotional intelligence) in comparison
      to the lower-risk group. Finally, the results and implications of the study are
      discussed in the light of designing prevention programs.

PMID- 18630651
TI  - Categorizing sources of risk and the estimated magnitude of risk.
AB  - The social perception of risk is considered a multidimensional task, yet little
      attention has been paid to the cognitive components that organize sources of
      risk, despite their having been discovered in various research studies. This
      study attempts to concretely analyze the cultural dimension involved in those
      processes. In the first phase, we tried to discover to what extent sources of
      risk are organized into the same categories by people from different countries.
      In order to do so, two groups of participants were formed: 60 Spanish psychology
      students and 60 Chilean psychology students classified 43 sources of risk into
      different groups according to the criteria they found appropriate. The two
      samples classified risk into identical groups: acts of violence, drugs,
      electricity and home appliances, household chemicals, chemicals in the
      environment, public construction projects, transportation, sports, and natural
      disasters. In a second study, 100 Spanish and 84 Chilean students were asked to
      evaluate the magnitude of the damage incurred by 17 sources of risk. In both
      groups, it was observed that the evaluation of damage resulting from each source
      of risk was affected by its category.

PMID- 18630653
TI  - Vicarious intergroup contact and the role of authorities in prejudice reduction.
AB  - The present study focuses on the effect of vicarious intergroup contact and the
      support of an authority figure on the improvement of outgroup and meta-stereotype
      evaluations. Meta-stereotype refers to the shared beliefs of ingroup members
      about how they consider outgroup members to perceive their group. Three
      preliminary studies were carried out to determine desirable and undesirable
      characteristics for a good basketball performance, the task that best
      demonstrates the application of these characteristics, and the two groups
      (basketball teams) that should be involved in the vicarious intergroup contact.
      Fans of one of the basketball teams participated in the current study. Vicarious
      intergroup contact improved outgroup and meta-stereotype evaluations as compared
      with a no contact condition. In addition, the positive effects of vicarious
      intergroup contact significantly increased when it was supported by an authority
      figure. More importantly, our study also shows that the improvement of outgroup
      evaluation was partially mediated by changes on meta-stereotypes.

PMID- 18630652
TI  - Condom use, contraceptive methods, and religiosity among youths of low
      socioeconomic level.
AB  - The purpose of this study was to investigate the relationship between the use of
      condoms and other contraceptive methods and religiosity/spirituality among youths
      of a low socioeconomic level in Porto Alegre. 1013 youths, between 12-24 years of
      age participated, responding to a personal questionnaire containing 109 items.
      Results show that 53.5% of these youths had already had their first sexual
      encounter, 55% of which had this experience before the age of 15. The majority
      (42.8%) claimed to be Catholic, and 26.7% said they believe in God, but were not
      religious. There appeared no significant difference in the use of condoms in
      relation to the level of religiosity, however, men used this method more than
      women to avoid AIDS and as a contraceptive. Women used other contraceptive
      methods more frequently, and there were no cases of exclusive use of methods
      permitted by the major religions (natural methods). This study revealed a high
      level of condom use (more than 80%) among both religious and non-religious
      youths.

PMID- 18630654
TI  - The sequential analysis of transgressors' accounts of breaking environmental
      laws.
AB  - Three-hundred and twenty written accounts of environmental transgressors were
      assessed by sequential analysis to reveal their argument streams. The accounts
      were obtained from the written statements that transgressors are allowed to give
      during the Spanish administrative process and which were included in files
      handled by four environmental law enforcement agencies. These agencies are
      distributed across national, regional, island and municipality jurisdictions. The
      setting for the study is a highly protected environment in which environmental
      laws have high salience. Results reveal that transgressors use simple argument
      streams, consistently more defensive than conciliatory, and questioning the
      perceived legitimacy of environmental law. It was seen also that the empirical
      functioning of the explanations related to pursuing emotional/prosocial
      objectives differs from what was expected from the traditional conceptual
      definition. Results are discussed in terms of how the assessment of the internal
      dynamic of the accounts would provide valuable information on transgressors'
      reasoning in relation to environmental laws.

PMID- 18630656
TI  - The mapping of Spanish social psychology through its conferences: a bibliometric
      perspective.
AB  - This study of papers gathered from the proceedings presented at Spanish social
      psychology conferences explores the use of bibliometrics for studying scientific
      disciplines. A reference database of all the papers included in the conference
      proceedings of events held from 1983 to 2000 was generated and classified by
      thematic area, paper type and author institutional affiliation. The references
      were laid out on contingency tables and mapped with correspondence analysis. The
      results show that there is a growing number of co-authored papers and a
      predominance of empirical over theoretical paper types. Some institutions have a
      higher concentration of theoretical papers while others work mostly in the areas
      of organizational and health psychology. In terms of empirical papers, there is a
      tendency towards generating more qualitative-based studies over the span of time
      captured by this work. There are also a number of papers written about such areas
      as cultural psychology that points to the emergence of an interest in critical
      social psychology. Concluding remarks underline the role of conferences and
      scientific meetings as an important indicator of the dynamic development of a
      scientific discipline.

PMID- 18630655
TI  - Family perception of the process of organ donation. Qualitative psychosocial
      analysis of the subjective interpretation of donor and nondonor families.
AB  - Family perception of organ donation has been explored by numerous authors using
      statements by the people who decided whether or not to donate the organs of a
      relative in a situation of brain death. Within this tradition, in this work, we
      analyze the discourse of six families who granted permission for organ donation
      and three who refused. We describe the process-based interpretation of this
      experience and identify psychosocial variables and processes that further our
      understanding of the decision finally adopted. We have identified two heuristics
      that guide family decision when organ donation is requested: the explicit or
      inferred will of the deceased and family attitudes to organ donation and
      transplant. It is postulated that the interaction of these two factors explains a
      large amount of the decisions made. We also hypothesize that a marked discrepancy
      between these two factors increases the importance of other aspects, especially
      the role of the transplant coordinator and of other healthcare personnel. These
      results support, at a social level, the implementation of transplant promotion
      programs; and at a healthcare level, the combined use of techniques of crisis
      intervention and attitude change.

PMID- 18630657
TI  - Both Freud and Hoffman are right: Anxious-aggressive and empathic dimensions of
      guilt.
AB  - The purpose of the study was to confirm a model which proposed two basic
      dimensions in the subjective experience of guilt, one anxious-aggressive and the
      other empathic, as well as another dimension associated but not intrinsic to it,
      namely, the associated negative emotions dimension. Participants were 360
      adolescents, young adults and adults of both sexes. They were asked to relate one
      of the situations that most frequently caused them to experience feelings of
      guilt and to specify its intensity and that of 9 other emotions that they may
      have experienced, to a greater or lesser extent, at the same time on a 7-point
      scale. The proposed model was shown to adequately fit the data and to be better
      than other alternative nested models. This result supports the views of both
      Freud and Hoffman regarding the nature of guilt, contradictory only at a first
      glance.

PMID- 18630658
TI  - Examining the relationship between binge eating and coping strategies and the
      definition of binge eating in a sample of Spanish adolescents.
AB  - The present study had two major goals: to explore the relationship between binge
      eating and coping strategies in a sample of Spanish adolescents and to examine
      the adolescents' concept of binge eating. Two hundred and fifty-nine adolescents
      from a secondary school completed the Adolescent Coping Scale (ACS; Frydenberg &
      Lewis, 1993) and the Bulimic Investigatory Test, Edinburgh (BITE; Henderson &
      Freeman, 1987), as well as additional questions regarding the binge-eating
      episodes. The results show that the adolescents who reported binge eating used
      more avoidance coping strategies than those who did not engage in this behavior.
      Adolescents took into account mainly the amount of food eaten when defining a
      binge with few of them mentioning loss of control in their descriptions, The
      results of the study have implications for the prevention of this behavior. The
      development of constructive ways for solving daily problems and coping with
      stressors may be a possible prevention strategy for this behaviour in
      adolescence.

PMID- 18630659
TI  - Relationships among goal orientations, motivational climate and flow in
      adolescent athletes: differences by gender.
AB  - The purpose of this investigation was to examine the relationships among
      perceived motivational climate, individuals' goal orientations, and dispositional
      flow, with attention to possible gender differences. A sample of 413 young
      athletes, ages 12 to 16 years, completed the Perceived Motivational Climate in
      Sport Questionnaire-2 (PMCSQ-2) and Perception of Success Questionnaire (POSQ),
      as well as the Dispositional Flow Scale. Task orientation was positively and
      significantly related to a perceived task-involving motivational climate and to
      the disposition to experience flow in the sport. Ego orientation was positively
      and significantly associated with a perceived ego-involving motivational climate
      and with dispositional flow. The perceptions of task-involving and ego-involving
      motivational climates were positively and significantly linked to general
      dispositional flow. Multiple regression analysis indicated that both task and ego
      goal orientations and perceived task- and ego-oriented climates predicted
      dispositional flow. Males displayed a stronger ego orientation, and were more
      likely to report that they participated in an ego-oriented climate, than did
      females. To the contrary, the females were more likely to perceive a task
      oriented climate than did the males. No meaningful differences were found between
      males and females in general dispositional flow.

PMID- 18630660
TI  - Reputation, loneliness, satisfaction with life and aggressive behavior in
      adolescence.
AB  - The present study analyses the relationship between adolescents' perception of
      reputation and aggressive behavior among peers. The sample is made up of 1319
      adolescents aged 11 to 16-years-old. Statistical analyses with structural
      equation modeling were carried out to examine the direct and indirect effect of
      perception of reputation (real and ideal) on aggressive behavior. Results
      indicate that adolescents' real and ideal reputations are related both directly
      and indirectly to aggressive behavior. The indirect effects suggest that
      loneliness and life satisfaction mediate the relationship between adolescents'
      reputation and their aggressive behavior. These findings and their implications
      are discussed.

PMID- 18630661
TI  - Morningness-eveningness in adolescents.
AB  - Individual morningness-eveningness differences explain the rhythmic variations of
      behavioral and biological patterns. Several studies have corroborated that
      morningness preference increases over adulthood and aging. Adolescents shift
      their time of day preferences from morningness to eveningness during puberty. The
      aims of this study were translate to Spanish the Morningness-Eveningness Scale
      for Children (MESC) and to analyze age and sex differences. A group of 600
      adolescents (aged between 12 and 16 years) participated in the study.
      Psychometric analysis showed that reliability and factor structure were suitable
      and similar to previous studies. The results indicated a clear decrease of
      morningness as of 12 years. Boys were more morningness-oriented than girls in
      several items of the questionnaire. In view of the results, several educational
      implications are raised.

PMID- 18630662
TI  - Perceived sexual harassment at work: meta-analysis and structural model of
      antecedents and consequences.
AB  - Although sexual harassment has been extensively studied, empirical research has
      not led to firm conclusions about its antecedents and consequences, both at the
      personal and organizational level. An extensive literature search yielded 42
      empirical studies with 60 samples. The matrix correlation obtained through meta
      analytic techniques was used to test a structural equation model. Results
      supported the hypotheses regarding organizational environmental factors as main
      predictors of harassment.

PMID- 18630663
TI  - Workplace mobbing and effects on workers' health.
AB  - In this work, we analyze various consequences of the phenomenon of mobbing on the
      health of a work sector with special characteristics: the agro fruit sector. For
      this purpose, we collected data from a sample of 396 workers (61 men and 331
      women) belonging to this sector in the Region of Murcia (Spain). A questionnaire
      with the following measurement instruments was administered: a Spanish adaptation
      of the revised Negative Acts Questionnaire (Saez, Garcia, & Llor, 2003), the
      Psychosomatic Problems Questionnaire (Hock, 1988), and a measure of absenteeism.
      The results revealed a significant and positive relation between workplace
      mobbing and psychosomatic symptoms, but not with absenteeism. The implications of
      the results for future research are discussed.

PMID- 18630664
TI  - Poverty, stressful life events, and coping strategies.
AB  - It was hypothesized that individuals of low socioeconomic status are exposed to a
      greater number of stressful events and therefore have a higher incidence of
      psychological disorders. However, the way they interpret, evaluate and cope with
      these stressful situations may either cause them to maintain, intensify or
      eliminate their overall stress. Past research indicates that the poorest
      individuals tend most frequently to falsely minimize or avoid stressful
      situations, which lowers the probability of resolving their problems. The
      objective of this study is to discover and compare the situations that have
      produced a high level of stress in subjects of three different socioeconomic
      groups over the last three months, as well as the strategies they used to cope,
      and their perceived effectiveness. The sample included 900 subjects of both sexes
      living in Mexico City. Among them, 346 were extremely poor, 260 were moderately
      poor and 312 were not poor. The results indicate that socioeconomic status is
      related to the frequency with which subjects report certain kinds of stressful
      situations. It was also found that non-poor subjects use problem-focused coping
      methods more than the other groups, while the poor use more emotionally-focused
      coping strategies, This article analyzes the strategies used by each group in
      each type of stressful situation reported.

PMID- 18630665
TI  - Psychological differences of patients and relatives according to post
      transplantation anxiety.
AB  - The aim of this investigation is to analyze the psychological differences of
      patients and their relatives according to the formers' post-transplantation
      anxiety. We used two groups of participants: transplant patients (n = 166) and
      close relatives (n = 166). Four questionnaires were applied: a Psychological
      Survey (to both groups), the Hospital Anxiety and Depression Scale, and the
      Quality of Life Questionnaire (to the transplant patients), and the Leeds Scales
      for the Self-Assessment of Anxiety and Depression (to the relatives).
      Participants were assessed twice: post-Intensive Care Unit (ICU; when patients
      were moved from the ICU to the Transplantation Unit) and post-hospital (one year
      after transplant). Results showed that high anxiety in patients just after organ
      transplant was related to an increase of anxiety and depression symptoms both in
      patients and relatives one year after transplant; it was also related to a
      decrease in the quality of life of these patients.

PMID- 18630666
TI  - Recurrent criminal behavior and executive dysfunction.
AB  - OBJECTIVE: To experimentally test the hypothesis that people who repeatedly
      participate in forms of non-violent crime exhibit an executive deficit detected
      in tests of high ecological validity, having changes in prefrontal functioning as
      neurophysiologic basis. PARTICIPANTS AND METHODS: A batteiy to assess executive
      dysfunction was administered--the Behavioural Assessment of the Dysexecutive
      Syndrome (BADS)--to an experimental group of 30 inmates convicted of crimes
      against property (mean age = 39.3, SD = 9.98), and a control group of 30 (mean
      age = 32.7, SD = 11.8), all male. RESULTS: The group of recurrent inmates
      performed significantly worse than the control group in their global scores on
      the battery, as well as in the majority of subscales. CONCLUSION: Without
      removing from consideration the fact that sample size was not very large and,
      primarily, alerting ourselves to the dangerous hypothesis of a "frontal
      criminogenesis," the authors interpret criminal recurrence and resistance to
      penal measures in terms of the scarcity of control that individuals from the
      experimental group have over their behavior and its respective consequences.

PMID- 18630667
TI  - Evaluation of Halpern's "structural component" for improving critical thinking.
AB  - Halpern (1998) proposed a four-component model for promoting the transfer of
      critical thinking. One of them, the "structural component," focuses on how to
      organize teaching so that critical thinking skills can be generalized. Here, we
      assess the efficiency of that type of organization. Thus, one group of university
      students received instruction following the suggestions specified in that
      component and their performance was compared with that of other university
      students who received instruction in the same skills but using a different
      procedure, and with that of a control group. In comparison with the control
      group, the performance of both instructed groups was better after training.
      However, no significant differences were observed between either instruction
      group; both forms of instruction afforded very similar results.

PMID- 18630668
TI  - Prediction of university students' academic achievement by linear and logistic
      models.
AB  - University students' academic achievement measured by means of academic progress
      is modeled through linear and logistic regression, employing prior achievement
      and demographic factors as predictors. The main aim of the present paper is to
      compare results yielded by both statistical procedures, in order to identify the
      most suitable approach in terms of goodness of fit and predictive power. Grades
      awarded in basic scientific courses and demographic variables were entered into
      the models at the first step. Two hypotheses are proposed: (a) Grades in basic
      courses as well as demographic factors are directly related to academic progress,
      and (b) Logistic regression is more appropriate than linear regression due to its
      higher predictive power. Results partially confirm the first prediction, as
      grades are positively related to progress. However, not all demographic factors
      considered proved to be good predictors. With regard to the second hypothesis,
      logistic regression was shown to be a better approach than linear regression,
      yielding more stable estimates with regard to the presence of ill-fitting
      patterns.

PMID- 18630669
TI  - Psychology of male and female communicative activity.
AB  - The article features a brief overview of theoretical and empirical studies in
      communication psychology and sociability of men and women, boys and girls.
      Russian and foreign studies are summarized to point out that girls and women
      place greater emphasis on communication and interpersonal relations than do boys
      and men. Moreover, female communication is more emotional. The article presents
      the results of the author's own empirical study of male and female communicative
      activity. Communicative activity is viewed as a complex psychological phenomenon,
      a degree of the subject's willingness to interact. Communicative activity was
      studied with the test proposed by the Russian psychologist, Krupnov, and designed
      to detect the following components of communicative activity: dynamic (natural),
      emotional, motivational, cognitive, regulatory, productive, and two sorts of
      communication difficulties (operational and personal). Gender differences in
      communicative activity are shown on a sample of 480 participants aged 18-40 (240
      men and 240 women). The article then describes communicative styles of
      adolescents (130 boys and 130 girls, aged 19-24). Various communicative styles
      are featured, including "energetic, businesslike," "conformal, emotional,"
      "diplomatic, externally oriented" for boys and "energetic, sociable," "emotional,
      difficult," and "complaisant, expressive" for girls. Every person's individuality
      and gender identity are shown to impact their communicative style.

PMID- 18630670
TI  - Assessment of vocational guidance: the Berufsbilder test.
AB  - The object of this study is to assess informative possibilities of some technical
      indicators of the Test of Photos of Professions (BBT--Berufsbilder test), a
      projective method to clarify professional inclination, proposed by Martin
      Achtnich. This psychological evaluation technique is composed of 96 photos of
      professionals, performing various types of activities. The test subject
      classifies the photos into three groups: positive (agreeable), negative
      (disagreeable) and indifferent (neutral). Among those chosen positively, five
      preferences are chosen and a story is developed that includes them, an activity
      that is requested two times during the Vocational Guidance process: in the
      beginning (or middle) and at the end of the intervention. In this study, 160
      stories were created by 80 youths, between 15 and 20 years of age, in public and
      private schools in a mid-sized Brazilian city. The stories were compared in three
      analytical categories: protagonist, professional conflict and resolution. The
      results were submitted to Wilcoxon nonparametric statistical analysis (p < .05),
      significant and relevant indicators of resolution being found in the process of
      occupational choice. This technical resource was shown, from this empirical
      evidence, to be promising for use in evaluation of intervention processes of
      Vocational Guidance.

PMID- 18630671
TI  - Reliability and validity of the Oxford Happiness Inventory among university
      students in Iran.
AB  - The aim of the present study was to examine the internal reliability, content
      validity, construct validity, and concurrent validity of the Persian
      translation/Farsi version of the Oxford Happiness Inventory. The Oxford Happiness
      Inventory and Fordyce Happiness Inventory were completed by a sample of 727
      Iranian university students. Findings confirmed the internal reliability,
      construct, and concurrent validity of the Oxford Happiness Inventory. Thus, it
      can be recommended for use as a trait-measure of happiness among Iranian samples.

PMID- 18630672
TI  - Spanish adaptation of the Stepparent Role Strain Index.
AB  - Stepparent role strain refers to the fragile position of these family members in
      stepfamilies due to the lack of clear social expectations about their roles. This
      ambiguity facilitates family conflict and a lack of stepparents' integration into
      the family system. The aim of this paper is to adapt a pioneer measure of
      stepparent role strain--the Stepparent Role Strain Index of Whitsett and Land
      (1992)--in a Spanish sample and to analyze its construct validity. The final
      instrument is made up of 26 items which have good internal consistency (alpha =
      .89) and an underlying six-factor structure, explaining 64.50% of the total
      variance.

PMID- 18630673
TI  - The semantic component of the evoked potential of differentiation.
AB  - This work analyzes data from recordings of (occipital and temporal) cortical
      evoked potentials (called evoked potentials of differentiation (EPD) occurring in
      humans in response to an abrupt substitution of stimuli. As stimuli we used three
      groups of words: the names of the ten basic colors taken from Newton's color
      circle; the names of seven basic emotions forming Shlossberg's circle of
      emotions; and seven nonsense words comprised of random combinations of letters.
      Within each group of word stimuli we constructed a matrix of the differences
      between the amplitudes of mid-latency components of EPD for each pair of words.
      This matrix was analyzed using the method of multidimensional scaling. As a
      result of this analysis we were able to distinguish the semantic and
      configurational components of EPD amplitude. The semantic component of EPD
      amplitude was evaluated by comparing structure of the data obtained to the
      circular structures of emotion and color names. The configurational component was
      evaluated on the basis of the attribute of word length (number of letters). It
      was demonstrated that the semantic component of the EPD can only be detected in
      the left occipital lead at an interpeak amplitude of P120-N180. The
      configurational component is reflected in the occipital and temporal leads to an
      identical extent, but only in the amplitude of a later (N180-P230) component of
      the EPD. The results obtained are discussed in terms of the coding of
      categorized, configurational, and semantic attributes of a visual stimulus.

PMID- 18630674
TI  - [Construction and expression characteristics in vitro of human papillomavirus
      type 16 E7 suicidal DNA vaccine].
AB  - OBJECTIVE: To construct the suicidal DNA vaccine of human papillomavirus type 16
      E7 gene (HPV16), and explore the DNA vaccine expression characteristics in vitro
      and capacity of inducing the transfected cells into apoptosis. METHODS: HPV16 E7
      gene cloned by PCR from pET32/E7 was inserted into the plasmid pSCA1 to construct
      the recombinant plasmid pSCA/E7, followed by identification with PCR, BamH I and
      Sma I digestion and sequencing. pSCA/E7 was then used to transfect BHK-21 cell
      line. The transient expression of HPV16 E7 gene was confirmed by immuno
      fluorescent staining, and the apoptosis induced by pSCA/E7 was checked with TDT
      mediated dUTP nick end-labeling (TUNEL). RESULTS: The cloned E7 gene fragment was
      about 400 bp in length. PCR, restriction endonuclease digestion and sequence
      analysis revealed that the HPV16 E7 gene was cloned into the eukaryotic
      expression plasmid pSCA1 successfully. Immunofluorescent staining confirmed that
      the E7 gene could express in BHK-21 cell line. The BHK-21 cells transfected with
      pSCA/E7 could be induced into apoptosis which was confirmed by TUNEL. CONCLUSION:
      The results show that HPV16 E7 suicidal DNA vaccine can express in BHK-21 cell
      line, and induce the pSCA/E7 transfected cells into apoptosis. These findings may
      provide the foundation for exploring the therapeutic vaccine against HPV16
      associated cervical cancer.

PMID- 18630675
TI  - [Construction of eukaryotic expression plasmid pEGFP-ATP1B1 and its effect on
      gastric adenocarcinoma cell SGC-7901].
AB  - OBJECTIVE: To establish the eukaryotic expression plasmid containing the code
      gene of Na+, K+-ATPase beta1-subunit (ATP1B1) and the basis of ATP1B1 applied to
      antitumor gene therapy. METHODS: The ATP1B1 cDNA was amplified from leukocyte
      gene library and then cloned into the eukaryotic expression vector pEGFP-C3. The
      recombinant plasmid, named as pEGFP-ATP1B1, was determined with restriction
      enzyme and sequencing analyses. Next pEGFP-ATP1B1 was transferred into gastric
      adenocarcinoma SGC-7901 cells by lipofectamine, then ATP1B1 mRNA expression in
      transfected cells was detected by real-time PCR, and also ATPase was detected
      after cell transfection, as well as the proliferation of such cells was measured
      by MTT. RESULTS: The analysis confirmed that the recombinant pEGFP-ATP1B1
      contained the ATP1B1 cDNA. After cell transfection, the expression of ATP1B1
      mRNA(129.2%) and the activity of ATPase [(2.95+/-0.210)%] were higher, and the
      growth of the SGC-7901 cells transfected with ATP1B1 was inhibited obviously when
      compared with the control group. CONCLUSION: The recombinant pEGFP-ATP1B1 is
      constructed successfully, and this recombinant eukaryotic expression vector could
      be used in additional studies on the biological effect of ATP1B1 and its use in
      anti-tumor gene therapy.

PMID- 18630676
TI  - [Effect of c-ski on biological behavior of rat skin-derived fibroblast].
AB  - OBJECTIVE: To observe the effect of oncogene c-ski on the cell viability,
      myofibroblast differentiation and type I collagen secretion of rat skin-derived
      fibroblast. METHODS: In situ expression of c-Ski in fibroblast was detected by
      immunohistochemistry. After cells transfected with c-ski gene, the changes of
      cell proliferation was measured with the method of MTT, the type I collagen
      secretion and myofibroblast differentiation were checked with the methods of
      immunohistochemistry and RT-PCR. RESULTS: There was obvious expression of c-Ski
      in fibroblast, which mainly located in nucleus. c-ski could promote cell
      proliferation in a dose-dependent manner, and also decrease mRNA and protein
      expression of type I collagen, but had no effect on myofibrblast differentiation.
      CONCLUSION: The roles of c-ski promoting cell viability and decreasing collagen
      secretion may have an important significance in accelerating wound healing and
      reducing scar formation.

PMID- 18630677
TI  - [Primary study on preparation and efficiency of neotype hepatocellular carcinoma
      dendritic cell vaccine with SOCS1 expression inhibited].
AB  - OBJECTIVE: To investigate the effect of SOCS1 expression inhibition on
      hepatocellular carcinoma-dendritic cell vaccine stimulated by LIGHT. METHODS: The
      dendritic cells (DC) were generated from mouse bone marrow (BMDC) by cultured in
      medium containing rmGM-CSF and rmIL-4. The vaccine cells were prepared by loaded
      with hepatocellular carcinoma HepA antigen and further treated with or without
      LIGHT and SOCS1 antisense oligonucleotide (AS1). For detecting the maturity of
      the vaccine cells, the expression of the cell's surface molecules CD40 and CD86
      were measured by FACS, and IL-12 and IL-1 secretion from the cells were
      determined by ELISA. And the CTL activity, cellular proliferation, IL-6 and TNF
      beta secretion levels of the vaccine-stimulated lymphocytes were also assessed
      for analyzing the immune response of lymphocyte. RESULTS: CD40 and CD86
      expression of the prepared vaccine cells were obviously enhanced by treatment of
      LIGHT and AS1, and so were IL-12 and IL-1 (P<0.01). It was also observed that CTL
      activity, cellular proliferation and IL-6 and TNF-beta secreting levels of
      lymphocytes that were stimulated by the vaccine cells treated with AS1 were
      notably enhanced. CONCLUSION: Inhibiting SOCS1 can improve the maturation of
      hepatocellular carcinoma-DC vaccine cell and can increase its inducing ability of
      anti-cancer immune response.

PMID- 18630678
TI  - [Effect of HSP90 function inhibited on the telomerase and P53 mutant in breast
      cancer cells].
AB  - OBJECTIVE: To investigate the effect of heat shock protein 90 (Hsp90) function
      inhibited on the telomerase activity and P53 expression in human breast cancer
      cells, in which a specific inhibitor geldanamycin (GA) was used to inhibit Hsp90
      function. METHODS: Human breast cancer cell line MDA-MB-435s was used for the
      study. Proliferation of MDA-MB-435s cells was measured with MTT assay. Cell cycle
      was analyzed by flow cytometry. The telomerase activity was measured by TRAP
      ELISA assay. The protein expression of mutant P53 in cells was detected by
      Western blot. RESULTS: GA inhibited the proliferation of MDA-MB-435s cells on a
      time- and dose-depending manner. After treated with GA, MDA-MB-435s cells
      arrested at G2/M phase. The telomerase activity of cells was decreasing, the
      expression level of mutant P53 protein in MDA-MB-435s cells was reduced obviously
      compared with that in control cells. CONCLUSION: The telomerase activation and
      mutant P53 expression in MDA-MB-435s cells are related to HSP90 function, of
      which the inhibition with GA can decrease the telomerase activity and the protein
      expression of mutant P53, and further repress the proliferation of MDA-MB-435s
      cells.

PMID- 18630679
TI  - [The study on oral carcinoma-associated fibroblast promoting the proliferation of
      lingual carcinoma cell line].
AB  - OBJECTIVE: The aim of this study was in vitro to investigate the effects of oral
      carcinoma-associated fibroblasts (CAFs) on the proliferation of lingual carcinoma
      cells. METHODS: The interaction model between primary oral CAFs and a lingual
      carcinoma cell line Tca8113 was established for this study project. The effects
      of CAFs on the viability and cell cycle of Tca8113 were investigated through
      morphological observation, MTT assay and flow cytometry. RESULTS: After oral CAFs
      interacted with Tca8113 directly, Tca8113 showed the cellular shape changes in
      morphology; compared with normal fibroblasts (NFs), CAFs enhanced the viability
      of Tca8113 (P<0.05), and increased the percentage of carcinoma cells in S phase
      and G2 phase (48.1% vs 40.0%). CONCLUSION: Oral CAFs can promote the
      proliferation of the lingual carcinoma cell line Tca8113 in vitro, and may play a
      key role in the progression of oral squamous cell carcinoma (OSCC).

PMID- 18630680
TI  - [Tanshinone II A inhibits in vitro cellular proliferation and migration of
      vascular smooth muscle cell of rabbit].
AB  - OBJECTIVE: To study the influence of Tanshinone II A on the proliferation and
      migration of rabbit vascular smooth muscle cell in vitro and to primarily probe
      into the mechanism of how Tanshinone II A works. METHODS: Rabbit aortic artery
      was chosen for primary culture of vascular smooth muscle cells (VSMC), which were
      used and divided into control and Tanshinone II A groups with different drug
      concentrations. After cells, according to the protocol, incubated with drug for
      24 h, 48 h or 72 h respectively, MTT assay was used to study the effect of
      Tanshinone II A on the VSMC proliferation; sterile scraper and contrast phase
      microscope were used to measure the distance of VSMC migration; analyses of cell
      cycle and DNA content were performed by flow cytometry. Then after TRITC
      phalloidin labeling for cytoskeleton filament (F-actin), the influence of
      Tanshinone II A on the cytoskeleton was revealed by laser confocal microscope.
      RESULTS: (1) At the same time point, Tanshinone II A inhibited the proliferation
      and migration of rabbit VSMCs in vitro significantly in a dose-dependent manner;
      (2) After 24 h, compared with control group Tanshinone II A increased the ratio
      of rabbit VSMCs in G0/G1 phase, and decreased DNA content significantly in a dose
      dependent manner; (3) Tanshinone II A influenced rabbit VSMCs cytoskeleton
      filament, including relatively short filaments arranged within nonpolarized cells
      and no lamellipodial protrusions, while in control group formation of
      lamellipodial protrusions and actin filaments parallel to long axis were seen.
      CONCLUSION; Tanshinone II A can significantly inhibit the proliferation and
      migration of rabbit VSMCs in vitro, which may result from arresting rabbit VSMCs
      through the check point of cell cycle, accumulating them in G0/G1 phase, inducing
      cell apoptosis and influencing the cytoskeleton filament.

PMID- 18630681
TI  - [Effects of free fatty acids on nitric oxide synthase activity and mRNA
      expression in endothelial cell of SD rat aorta].
AB  - OBJECTIVE: To test the hypothesis that free fatty acids (FFA) induced endothelial
      dysfunction might relate with the inhibitions of endothelial nitric oxide
      synthase (eNOS) mRNA expression and activity, and to explore the possible
      pathogenic mechanisms. METHODS: Male SD rats underwent 6 h infusion in two
      groups: Normal control (NC, n=20) infused with saline; FFA group (n=20) infused
      with 20% intralipid + heparin. Blood samples were collected at the end of
      infusion so as to measure the concentrations of FFA, nitrogen oxides (NOx),
      reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH)
      and high sensitivity C-reactive protein (hs-CRP). The eNOS activity and mRNA
      expression were analyzed with aortic endothelial homogenate. RESULTS: In FFA
      group, the plasma FFA concentration was higher [(1146.4+/-336.6) micromol/L vs
      (345.5+/-113.6) micromol/L, P<0.01] while the NOx level was lower [(14.3+/-1.9)
      micromol/L vs (19.3+/-2.9) micromol/L, P<0.01]. The serum concentrations of ROS,
      MDA, hs-CRP were elevated in FFA group when compared with controls [ROS: (864.3+/
      135.4) mmol/L vs (452.4+/-90.5) mmol/L, P<0.05; MDA: (8.05+/-1.69) nmol/L vs
      (5.53+/-0.43) noml/L, P<0. 05; hs-CRP: (0.35+/-0.04) mg/L vs (0.21+/-0.03) mg/L,
      P<0.053] while GSH level was significantly declined in FFA group [(153.1+/-55.9)
      mg/L vs (171.9+/-60.5) mg/L, P<0.05]. Both the eNOS mRNA level and eNOS activity
      in endothelial homogenate were decreased in FFA group [eNOS mRNA/beta-actin: 1.42
      vs 2.12, P<0.01; eNOS activity: (1.15+/-0.42) pmol/(min x mg) vs (2.43+/-0.56)
      pmol/(min x mg), P<0.01]. CONCLUSION: The eNOS mRNA expression and activity may
      be inhibited by elevated circulating FFAs concentration, of which mechanisms may
      be related to the increased oxidative stress and moderate inflammation.

PMID- 18630682
TI  - [Morphological and functional characteristics of pancreatic islet beta cells in
      natural aging SD rats].
AB  - OBJECTIVE: To evaluate the effect of aging on metabolic profile and the changes
      in morphology and secreting function of beta-cell. METHODS: SD rats with
      different ages (5-6, 11-12, 20-24 Mon.) were used in this experiment to detect
      fasting blood glucose, lipid profile and free fatty acids (FFA) as metabolic
      parameters. Islet population and beta-cell shape from different age groups were
      assessed by immunohistochemistry and electron microscope (EM), respectively.
      Moreover, isolated rat islets from different ages were purified and cultured with
      two culture medium containing 5. 6 mmol/L and 16.7 mmol/L glucose over 24 hours,
      respectively. The secreted levels of insulin at 2, 4, 6, 24 hours were measured
      by radioimmunoassay (RIA). RESULTS: (1) The significantly higher concentration of
      FFA was found in 11-12, 20-24 months groups (386.02+/-88.08; 349.43+/-93.47 vs.
      263.93+/-68.77 mmol/L, respectively, P<0.05), with no difference in WT, FBG,
      lipid profile among three groups; (2) Insulin secretion by glucose (5.5 mmol/L)
      stimulating old rats showed lower peak value than younger counterparts did
      [6.40+/-2.7 vs. 13.97+/-1.23 (6 Mon.) & 12.08+/-0.76 (12 Mon.) mU/L x 30 islets]
      and so did another glucose (16.7 mmol/L) group [6.75+/-4.69 vs. 13.41+/-0.72 (6
      Mon.) & 13.56+/-0.60 (12 Mon.)]. (3) The ratio of beta-cell mass to islet was
      slightly larger in old rats than in younger rats (72.99+/-29.65% vs. 67.76+/
      23.48% (12 Mon.) & 61.69+/-30.12% (6 Mon.), P>0.05); The expression of insulin
      measured by immunohistochemistry was dramatically decreased in old rat islet
      compared with 5-6, 11-12 month rats [242.71+/-95.37 (24 Mon.), 309+/-83.99 (12
      Mon.) vs. 558+/-69.94 (6 Mon.), P<0.05]. CONCLUSION: Older rats showed higher FFA
      and age-related impairment of insulin secretion with or without the glucose
      stimulation. These findings suggest that insulin therapy should be taken into
      account for elder earlier once type 2 diabetes is diagnosed.

PMID- 18630683
TI  - [Apoptosis of neuroglial cell and expressions of neurite outgrowth inhibitor B
      and MAP kinase-activated protein kinase 2 in white matter damage model of newborn
      rat brain].
AB  - OBJECTIVE: To observe and explore the apoptosis of neuroglial cell and the
      expression changes of neurite outgrowth inhibitor B (Nogo-B) and MAP kinase
      activated protein kinase 2 (MK2) in SD rats with white matter damage (WMD).
      METHODS: The WMD model of newborn rat was established for this study, and then
      the pups were respectively killed at 30 min, 1 h, 4 h, 12 h, 1 d, 3 d, 7 d, 14 d,
      21 d after WMD. The apoptosis of neuroglial cells was investigated by TUNEL
      method; the changes of Nogo-B expression in white matter were investigated by
      immunohistochemical technique; the changes of expression of MK2 mRNA in white
      matter were measured by in situ hybridization. RESULTS: TUNEL result showed the
      number of apoptotic cells increased at 4 h and peaked at 3 d, decreased at 7 d
      after WMD of newborn rat; the expression of MK2 mRNA began to increase at 1 h and
      reached a maximum at 3 d (P<0.05); the expression of Nogo-B in periventricular
      white matter and corpus callosum of WMD rat was up-regulated at 12 h and peaked
      at 3 d after cerebral white matter damage, displaying significant differences at
      12 h, 1 d, 3 d and 7 d when the Nogo-B expression in WMD rat compared with that
      observed in the control (P<0.05). CONCLUSION: Nogo-B and MK2 can participate in
      pathogenesis of white matter damage in newborn rat.

PMID- 18630684
TI  - [Impacts of tetramethylpyrazine on BDNF, bFGF expression and neuron-protection in
      severe brain injury tissue of rat].
AB  - OBJECTIVE: To observe the expression levels of BDNF and bFGF, the variation of
      superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and injury neuron
      of rat, and to evaluate the effect of Tetramethylpyrazine (TMP) on neuro
      protection finally. METHODS: 120 SD rats were randomly assigned into three
      groups: pseudo-operation group, severe brain injury model group and TMP treatment
      group. Every group contained 40 rats. The severe brain injury (SBI) of rat was
      established according to Feeney' s method. The treatment group was administrated
      with TMP transperitoneally. Rats were killed at 7 h, 24 h, 72 h, 168 h
      respectively after SBI. BDNF, bFGF, Nissl body and neurofunction were detected in
      every group at all the time scales. MDA and SOD of serum were also detected by
      radical immunoassay. RESULTS: After rat SBI treated with the administration of
      TMP, the expression of BDNF and bFGF increased significantly in the injured brain
      tissue (P<0.05), and the MDA level showed to be decreased but the SOD was
      increased in serum (P<0.05). The Nissl body and neuro-function were well
      protected. CONCLUSION: TMP may protect the rat cerebral neurons from SBI.

PMID- 18630685
TI  - [Effects of tetramethylpyrazine on endothelin and nitric oxide contents in plasma
      and cerebrospinal fluid after subarachnoid hemorrhage].
AB  - OBJECTIVE: To observe the variation of endothelin (ET) and nitric oxide (NO) in
      plasma and cerebrospinal fluid (CSF) in rabbits, and evaluate the effects of
      tetramethylpyrazine (TMP) on the prevention and cure of cerebral vasospasm (CVS)
      after subarachnoid hemorrhage (SAH). METHODS: 24 New Zealand rabbits were
      randomly assigned into three groups: contrast group, experiment group and blank
      group. Every group contained 8 rabbits. SAH was established according to inject
      blood into the cisterna magna. The experiment group was administrated with TMP
      (20 mg/kg x d) transperitoneally. ET and NO of plasma and CSF were detected by
      radical immunoassay at 72 h and 168 h after SAH. Neurofunction were detected in
      every group at all the time scales. RESULTS: (1) After SAH, the level of ET in
      CSF increased significantly in contrast group compared with that in experiment
      and blank groups (P<0.05). The value of ET at 168 h was higher than that at 72 h.
      The level of ET in plasma increased significantly in contrast group compared with
      blank and experiment groups (P<0.05), and no significant contrast could be found
      between blank and experiment group. (2) After SAH, the value of NO in CSF was
      lower in contrast group than in other groups (P<0.05), and the level of NO in CSF
      continued to decrease in all groups on some extent. As time went by, no
      significant contrast could be found in all groups. The value of NO in plasma was
      lower in contrast group than in other groups (P<0.05). There was no significant
      difference between experiment and blank groups. (3) The neuro-function score
      continued to be increased in contrast group, but decreased in experiment one. The
      neuro-function score was lower in experiment group than in contrast one at every
      time point (P<0.05). CONCLUSION: After administration of TMP, the variation of ET
      has the continued decrease in plasma and CSF; the variation of NO shows the
      continued increase in plasma and CSF; neurological function gets possibly
      protected. TMP may prevent from and cure CVS after SAH.

PMID- 18630687
TI  - [The effect of ginsenoside Rg1 on the renal interstitial fibrosis of UUO rat].
AB  - OBJECTIVE: To study the effect of ginsenoside Rg1 on the renal interstitial
      fibrosis caused by unilateral ureteral obstruction (UUO) of rats. METHODS: 80
      healthy Sprague-Dawley rats were randomly divided into 4 groups: the UUO group
      (UUO), sham-operation group (SOR), ginsenoside Rg1 group (Rg1) and losartan group
      (ARB). From the first day after initial UUO, ARB group was intragastrically
      administrated with losartan 20 mg/(kg x d). UUO, Rg1 and SOR groups were
      intragastrically administrated with identical volume of normal saline. Rg1 group
      was intraperitoneally injected with ginsenoside Rg1 50 mg/(kg x d). UUO, ARB and
      SOR groups were intraperitoneally injected with identical volume of normal
      saline. At day 3, 7, 14 after UUO, 6 rats selected randomly from each group were
      killed. The dynamic histological changes of renal interstitial tissues were
      observed by HE, Masson and PAS staining. The mRNA of transforming growth factor
      beta1 (TGF-beta1) was quantified by real-time PCR. The protein levels of TGF
      beta1 expression were assessed by Western blot and immunohistochemical method
      respectively. RESULTS: In UUO kidneys, the interstitial fibrosis including
      tubular atrophy, loss and dilation, inflammatory cell infiltration and
      interstitial matrix deposition was prominent. However, these morphological
      changes were notably reduced in Rg1 and ARB groups, and there was no significant
      difference between the two groups (P > 0.05). TGF-beta1 mRNA and protein
      expression were increased dramatically for UUO group at postoperative day 7 and
      14 (P < 0.05). TGF-beta1 expression in Rg1 and ARB groups were significantly
      lower than that in UUO group (P < 0.05). CONCLUSION: Ginsenoside Rg1 can
      evidently inhibit UUO-induced renal interstitial fibrosis in rat, which may be
      related to the down regulation of TGF-beta1 expression.

PMID- 18630686
TI  - [Effects of Ginsenoside RB1 on neural cell apoptosis and expressions of Bcl-2 and
      Bax in rats following subjected to cerebral ischemia-reperfusion].
AB  - OBJECTIVE: To observe the effects of Ginsenoside Rb1 (GRb1) on neuronal cell
      apoptosis and the expressions of Bcl-2 and Bax in rats after cerebral ischemia
      reperfusion so as to investigate the neuroprotective mechanism of GRb1. METHDOS:
      The model of cerebral ischemia-reperfusion was established by occluding rat
      middle cerebral artery for 2 h. The rats were randomly divided into two groups:
      ischemia-reperfusion group (I/R group) and GRb1 treat group (GRb1 group). GRb1
      (40 mg/kg, i.p.) was administered immediately to rats after the onset of
      reperfusion. Two groups were further subdivided 7 subgroups according to various
      reperfusion time (3 h, 12 h, 1 d, 2 d, 3 d, 5 d and 10 d, n=4 per time point). HE
      staining was used to observe histological features. TUNEL and immunohistochemical
      method were used to analyze the cell apoptosis and expressions of Bcl-2 and Bax,
      respectively. RESULTS: Compared with I/R group, GRb1 reduced pathological
      changes, and decreased the number of apoptotic neural cells (P<0.05 on 12 h, 1 d,
      2 d and 3 d) and up-regulated the number of Bcl-2 positive cells (P<0.05 on 12 h,
      1 d, 3 d, 5 d and 10 d), and meanwhile down-regulated the number of Bax positive
      cells (P<0.05 on 3 h, 12 h, 1 d, 2 d, 3 d, 5 d and 10 d) in the ipsilateral
      hemisphere. CONCLUSION: The neuroprotective effect of GRb1 on cerebral ischemia
      reperfusion injury is related to inhibit neuronal apoptosis and to up-regulate
      the expression of Bcl-2 with down-regulating the expression of Bax.

PMID- 18630688
TI  - [Effects of valsartan on the renal vascular endothelial growth factor and its
      receptor flk-1 of diabetic rats].
AB  - OBJECTIVE: To explore effects of valsartan on expression changes of vascular
      endothelial growth factor (VEGF) and its receptor Flk-1 in diabetic rat kidney.
      METHODS: To establish the diabetic nephropathy (DN) rat models and divide the
      experiment rats into three groups--the DN group, the valsartan group and the
      control group, and use the reverse transcriptase polymerase chain reaction (RT
      PCR), Western Blotting and immunohistochemical techniques to detect the
      expression of VEGF and Flk-1, and detect the urine protein and glomerular area
      and volume, then analyze the relationship of the data. RESULTS: The mRNA and
      protein expression of VEGF and Flk-1, the urine protein and glomerular area and
      volume in the DN were higher than those in the control group and valsartan group
      (P < 0.05). VEGF and Flk-1 were positively correlated with the urine protein and
      glomerular area and volume (P < 0.05). CONCLUSION: VEGF and Flk-1 play an
      important role in the pathogenesis of DN, of which over-expression may lead to
      the damage of kidney. The angiotensin II receptor antagonist--valsartan can
      protect kidney through the non-hemodynamic mechanism of inhibiting the abnormal
      expression of VEGF and Flk-1.

PMID- 18630689
TI  - [The change of fractalkine in lung tissue of rat with hypoxic pulmonary
      hypertension].
AB  - OBJECTIVE: To evaluate the role of fractalkine in the pathogenesis of hypoxic
      pulmonary hypertension. METHODS: Twenty male SD rats were randomly divided into
      control group and hypoxic group. Rats in hypoxic group were exposed to hypoxia
      for 3 weeks. Mean pulmonary arterial pressure (mPAP) was measured by a right
      cardiac catheterization. The thickness of pulmonary arterioles was measured with
      a computerized image analyzer. The rates of wall thickness/external diameter
      (WT%) and wall area/total vascular area (WA%) were calculated. The fractalkine
      level in lung tissue were measured by enzyme-linked immunosorbent assay.
      Fractalkine mRNA expression in lung were observed by reverse transcriptase
      polymerase chain reaction. RESULTS: The rat mPAP of hypoxic group was higher than
      that of the control group [(28.7 +/- 3.8) mmHg vs (16.3 +/- 2.1) mmHg, P < 0.01].
      The WT% and WA% were increased significantly in hypoxic group than in control
      group (WT%: (21.28 +/- 4.60)% vs (10.20 +/- 1.56)%, WA%: (67.08 +/- 9.44)% vs
      (38.11 +/- 42.30)%, P < 0.01, respectively]. In hypoxic group, the expression of
      fractalkine mRNA in the lung was significantly up-regulated [(0.49 +/- 0.05) vs
      (0.29 +/- 0.02), P < 0.01], the expression level of fractalkine in lung tissue
      was higher than that in control group [(7622.6 +/- 938.4) pg/mL vs (4168.5 +/-
      403.5) pg/mL, P < 0.01. Linear correlation analyses showed that fractalkine mRNA
      and protein were positively associated with WA% and WT% (P < 0.05). CONCLUSION:
      The synthesis and release of fractalkine are increase in the lung tissue of
      chronic hypoxic rats, and fractalkine may play an important role in hypoxic
      pulmonary hypertension.

PMID- 18630690
TI  - [Effect of gefinitib on airway mucus hypersecretion induced by acrolein in rats].
AB  - OBJECTIVE: To test the effect of gefinitib, an EGFR-TKI, on airway mucus
      hypersecretion induced by acrolein in rats. METHODS: Thirty six rats were
      randomly divided into six groups, each with six rats. Group A did not get any
      intervention; group B had airway mucus hypersecretion induced by inhaled
      acrelein; Gefitinib intervention was given to group C, D, and E, with a dose of
      10 mg/kg,20 mg/kg, and 30 mg/kg of gefitnib administered by gavage, respectively,
      30 min before exposure to acrolein inhalation; group F served as a control group,
      with gefitinib (30 mg/kg) administered by gavage 30 min before exposure to saline
      inhalation. After three weeks, the rats were sacrificed. The lung tissue sections
      were obtained. The immunohistochemistry and RT-PCR were performed to detect the
      MUC5AC and its mRNA expression. The EGFR was detected by immunohistochemical
      staining. The goblet cells were identified with Alician Blue-periodic Acid Schiff
      (AB-PAS). RESULTS: Overexpression of MUC5AC, EGFR and increased goblet cells in
      the lungs of the rats were found in the rats exposed to acrolein inhalations.
      Gefitinib intervention inhibited the expression of MUC5AC and the increase of
      goblet cells induced by acrolein. Gefitinib also reduced the expression of EGFR
      in the lungs. CONCLUSION: Acrolein increases the expression of MUC5AC through
      activating EGFR, which indicates that EGFR-TKI such as gefitinib can be useful in
      the treatment of mucus hypersecretion by regulating the signal transduction
      pathways of EGFR.

PMID- 18630691
TI  - [Effect of N-acetylcysteine on lipopolysaccharide stimulating IL-8 expression of
      human uterine smooth cell].
AB  - OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC)on the expression
      of IL-8 and the activity of NF-kappaB, which are induced by lipopolysaccharide
      (LPS) in human uterine smooth cell. METHODS: Human uterine smooth cells were
      primarily cultured and stimulated by LPS after pretreated by 5,10,15 mmol/L NAC
      and normal saline (NS). ELISA was performed to measure the expression of IL-8
      protein in supernatants and RT-PCR was used to detect the IL-8 mRNA expression.
      The expression of NF-kappaB P65 protein was detected by Western Blotting.
      Furthermore, the expression of IL-8 mRNA and protein were detected at 0, 3, 6,
      12, 24 and 48 h after LPS challenge in human smooth cell pretreated by 10 mmol/L
      NAC. RESULTS: (1) NAC significantly inhibited IL-8 mRNA expression and production
      in human uterine smooth cells with a concentration-dependent way (5-15 mmol/L).
      (2) The decreasing expression of NF-kappaB P65 protein was accompanied with
      increasing concentration of NAC in accordance with IL-8 mRNA (P < 0.01).
      CONCLUSION: NAC may inhibit the induction IL-8 gene and protein by LPS inhibiting
      NF-kappaB activation in human uterine smooth cell.

PMID- 18630692
TI  - [The influence of different glucose concentrations on cellular activity of human
      osteosarcoma cell line MG63].
AB  - OBJECTIVE: In this research, we took an insight into the influence of different
      glucose concentrations on human osteosarcoma cell line MG63, hoping to give an
      explanation to the mechanism of the osteoporosis (OP) caused by diabetes mellitus
      (DM). METHODS: Four culture media of different glucose concentrations, 5.5
      mmol/L, 10 mmol/L, 20 mmol/L, 40 mmol/L, were set up for this study. Human
      osteosarcoma cell line MG63 was cultured in these media successively for 21 d,
      and then the proliferation rate of cells, secretion of ALP and BGP, percentage of
      apoptosis cells and the formation of calcified nods were observed and measured.
      RESULTS: The elevated glucose concentration prompted the proliferation of MG63
      cells, but the activities of MG63 cells were not correspondent with the cell
      number. On the contrary, the secretion of ALP, BGP and the mineralization of the
      MG63 cells were decreased. The apoptosis of the cells was promoted. CONCLUSION:
      From our study, we confirmed the toxicity of hyperglycemia to MG63 cells. It
      suggested that the tight control of the serum glucose can be a good method to
      prevent the occurrence of osteoporosis.

PMID- 18630693
TI  - [Activity detection and immunohistochemistry study on xanthine oxidase in
      pathological scars].
AB  - OBJECTIVE: To study the change of xanthine oxidase in pathological scars.
      METHODS: The tissues of hypertrophic scar (10 cases), keloid (10 cases) and
      normal skin (8 cases) were collected for this project, in which the content of
      malonaldehyde, the activity of xanthine oxidase and total of antioxidant capacity
      were detected by spectrophotometric method. The expression of xanthine oxidase
      was evaluated by immunohistochemistry technique. RESULTS: Compared with normal
      skin tissue, the content of malonaldehyde and xanthine oxidase activity were
      significantly higher in pathological scars (P < 0.05), but no significant
      difference was observed in the decrease of total antioxidant capacity.
      Differences in above-mentioned indexes all were not remarkable between
      hypertrophic scars and keloids. Immunohistochemical study indicated that the
      expressions of xanthine oxidase in the epidermal keratinocytes and dermal
      fibroblasts of pathological scars increased markedly in contrast with normal skin
      (P < 0.05). CONCLUSION: The xanthine oxidase activity shows to be increased in
      pathological scars, and the xanthine oxidase expressions are enlarged in
      epidermal keratinocytes and dermal fibroblasts of pathological scars, which may
      be a reason resulting in the increase of free excessive growth of scar tissues.
      radical level, and may play a role in pathogenesis of excessive growth of scar
      tissues.

PMID- 18630694
TI  - [Effect of subchronic administered Bismerthlazol on thyroid glands of rats].
AB  - OBJECTIVE: To test the impact of subchronically administered Bismerthlazol on the
      thyroid morphosis of rats. METHODS: One hundred SD rats were randomly divided
      into one negative control group and four experimental groups with 7.0, 27.9,
      111.7, and 447.0 mg/kg daily doses of Bismerthlazol, respectively. The
      Bismerthlazol was administered by gavage for 90 d. At the end of the experiment,
      the thyroids of the rats were harvested and weighted. The pathological changes of
      the thyroids were observed under light microscopes. The positive expression of
      PCNA in the thyroid glands were examined by histochemistry methods. RESULTS:
      Increased coefficients of thyroid gland weight were found in the experimental
      groups (P < 0.01). The thyroid glands showed different hyperplasia of follicular
      cells. Increased positive cells of PCNA were observed in the experimental groups
      (P < 0.05 or P < 0.01) except for the 7.0 mg/kg dose group. CONCLUSION: Long-time
      administered Bismerthlazol causes thyroids hyperplasia in rats. Further study on
      the mechanisms is warranted.

PMID- 18630695
TI  - [Study on the expression of matrix metalloproteinase-9 in lung fibroblasts of rat
      with acute paraquat poisoning].
AB  - OBJECTIVE: To investigate the expression and effect of matrix metaloproteinases-9
      in lung injury of rats with acute paraquat poisoning. METHODS: 50 SD rats were
      randomly divided into control group and poisoned group. At 1, 3, 7, 14, 28 days
      after exposed to paraquat, five rats of each group were used to assess lung
      pathological changes, and the expression of MMP-9 mRNA in lungs was evaluated by
      RT-PCR. RESULTS: (1) The expressions of MMP-9 protein and mRNA markedly increased
      at the first day of paraquat poison, reached the peak at the 7th day, decreased
      slowly afterwards. (2) The expressions of MMP-9 protein and mRNA markedly
      increased at 1, 3, 7 days. The protein expression of MMP-9 returned to baseline
      level at the 28th day, and mRNA expression of MMP-9 returned to baseline at the
      14th day. CONCLUSION: The expression of MMP-9 in lung fibroblasts is up-regulated
      in silicotic fibrosis model.

PMID- 18630696
TI  - [The expression of BDNF and PSD-95 in hippocampal CA1 region of morphine
      withdrawn rat with different dependent times].
AB  - OBJECTIVE: To observe the expression of brain-derived neurotrophic factor (BDNF)
      and postsynaptic density-95 (PSD-95) in hippocampal CA1 region of rat with
      morphine dependence for different times and withdrawn for 1 week, and investigate
      the influence of that morphine dependence is withdrawn on rat hippocampal CA1
      area. METHODS: Animal models of rats with morphine withdrawal for 1 week and
      different morphine dependent times(1 week, 2 weeks, 4 weeks) were established.
      The expression of BDNF and PSD-95 in hippocampal CA1 were identified with RT-PCR.
      RESULTS: The expression of BDNF and PSD-95 in hippocampal CA1 decreased in the
      withdrawn group with morphine dependence for 1 week as compared with that in
      normal saline (NS) group (P < 0.01), and it increased in the withdrawn group with
      morphine dependence for 2 weeks as compared with that in morphine-dependent group
      for 1 week (P < 0.05) but still decreased as compared with that in NS group (P <
      0.01), and it decreased in the withdrawn group with morphine dependence for 4
      weeks as compared with the other three groups (P < 0.01). CONCLUSION: The
      expression of BDNF and PSD-95 in hippocampal CA1 decreases in morphine-depended
      rats withdrawn for 1 week. Morphine withdrawal has a manifest harm in hippocampal
      CA1 region of rat.

PMID- 18630697
TI  - [Effects of different intensity pulsed electromagnetic fields on serum estradiol
      of ovariectomized rats].
AB  - OBJECTIVE: To explore the effects of different intensity pulsed electromagnetic
      fields (PEMFs) on serum estradiol in ovariectomized rats. METHODS: Fifty female
      SD rats were randomly divided into five groups: sham-operated control (no PEMF
      treatment), ovariectomized control(no PEMF treatment),ovariectomized group I, II,
      III (PEMF treatment at 8 Hz frequency and 0.77 mT, 3.82 mT, 9.87 mT intensity, 40
      min daily for 30 days). Except for the sham-operated control rats, a standardized
      ovariectomy was used on every rat of other groups. The serum estradiol(E2) of
      rats was assessed at 30 days after PEMF treatment. RESULTS: The E2 values of the
      SHAM control group were significantly higher than those of other four groups (P <
      0.05 or P < 0.01), but the difference in E2 values was not significant among the
      other four groups (P > 0.05). CONCLUSION: PEMFs can not improve the serum
      estradiol level of ovariectomized rat, it shows that the therapeutical effect of
      PEMFs is not due to improve the serum estradiol level.

PMID- 18630698
TI  - [Model establishment for emulsified isoflurane delivered selectively to the goat
      spinal cord and preliminary research on the immobility mechanism of isoflurane].
AB  - OBJECTIVE: To develop a new model of preferentially delivering isoflurane to the
      goat spinal cord, and to explore preliminarily volatile anesthetic action sites.
      METHODS: Eighteen goats were randomly and equally divided into group artery and
      group vein. In group artery, emulsified isoflurane was infused into descending
      aorta for developing the model to deliver isoflurane to the goat spinal cord. In
      group vein, emulsified isoflurane was infused via the ear vein. After the end
      tidal isoflurane concentration of 1 minimum alveolar concentration (MAC) was
      maintained for 20 min, the isoflurane partial pressures (P(iso)) in samples which
      were drawn from the femoral artery and the carotid artery were determined by a
      gas chromatography. RESULTS: In group vein, there was no statistical difference
      among all the P(iso). In group artery, the P(iso) of the femoral arterial blood
      was almost same as that in group vein, but the P(iso) of the carotid arterial
      blood was near half of that in group vein [(6.07 +/- 3.60) mmHg vs (10.21 +/-
      2.41) mmHg, P < 0.05]. CONCLUSION: This new model permits preferentially to
      deliver the isoflurane to the in situ goat spinal cord, and the results support
      the importance of the spinal cord in suppressing nociceptive reflex under
      isoflurane anesthesia.

PMID- 18630699
TI  - [Phylogeny analysis and identification of two bacterial strains sourcing from
      human intestine and having resistance to acid and bile].
AB  - OBJECTIVE: To screen bacteria for the engineering bacteria expressing and
      secreting high activity beta-galactosidase, and two bacterial strains called as
      R92-2 and R111 with acid and bile resistances would be isolated from health human
      intestine to strain identification and phylogenetic analysis. METHODS: These two
      strains were first been identified with phenotype characteristic analysis. Then
      the 16S rDNAs of these two bacterial strains were amplified and sequenced with
      the primers designed by the conserve sequences. DNA sequences were blasted
      against GenBank, and the phylogenetic trees were constructed. RESULTS: Phenotype
      characteristic analysis showed that both of the bacterial strains belonged to
      lactic acid bacteria. Results of Blastn showed that 16S rDNAs of R92-2 and
      Weissella cibaria had 100% homology; 16S rDNAs of R111 and Enterococcus faecium
      had 100% homology too. CONCLUSION: R92-2 belongs to Weissella cibaria strain;
      R111 belongs to Enterococcus faecium strain. These two stains may be used to
      construct the engineering bacteria expressing and secreting high activity beta
      galactosidase.

PMID- 18630700
TI  - [Effects of high-carbohydrate/low-fat diet on serum lipid ratios in healthy young
      subjects].
AB  - OBJECTIVE: To investigate the effects of the short-term high-carbohydrate/low-fat
      (HC/LF) diet on the serum lipid ratios of healthy young subjects, which meant
      triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), the logarithm of
      TG/HDL-C [log (TG/HDL-C)], low-density lipoprotein cholesterol to high-density
      lipoprotein cholesterol (LDL-C/HDL-C), and total cholesterol to high-density
      lipoprotein cholesterol (TC/HDL-C). METHODS: 56 healthy participants with the
      average age of (22.89 +/- 1.80) years took the normal diet for 7 days followed by
      HC/LF diet for 6 days. Venous blood samples in fasting were collected between 7 :
      00 and 10 : 00 AM on the 1st, the 8th and 14th day, respectively. Serum
      concentrations of triglyceride (TG), total cholesterol (TC), high density
      lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C)
      were measured by regular methods. The ratios of TG/HDL-C, log (TG/HDL-C), LDL
      C/HDL-C, and TC/ HDL-C were calculated. RESULTS: After HC/LF diet, both TG/HDL-C
      and log (TG/HDL-C) increased significantly for females (P < 0.05). For the males,
      these two ratios were decreased although not significant in statistics. When BMI
      or WHR was taken into account, the two ratios increased significantly after HC/LF
      diet, but only for the normal females (P < 0.05), not for the females with
      overall or abdominal adiposity. No significant changes of TG/HDL-C and log(TG/HDL
      C) after HC/LF diet were observed between the males with different BMI or WHR.
      TC/HDL-C and LDL-C/HDL-C decreased significantly (P < 0.05) after HC/LF diet, but
      these changes were not found to associate with gender, BMI or WHR. CONCLUSION:
      The changes of TG/HDL-C and log (TG/HDL-C) induced by the short-term HC/LF diet
      are different in healthy young subjects with different gender, BMI or WHR, but
      there is no significant change happening to TC/HDL-C and LDL-C/HDL-C.

PMID- 18630701
TI  - [Change of serum endogenous digitalis-like substance undergoing cardiopulmonary
      bypass].
AB  - OBJECTIVE: To investigate the plasma concentrations and cardiac effects of
      endogenous digitalis-like substance (EDLS) before and after cardiopulmonary
      bypass (CPB). METHODS: 29 adults patients with NYHA II - IV, who suffered from
      congenital and acquired heart diseases, were included in this study. The plasma
      EDLS levels were determined by radioimmunoassay before and at the end of CPB, 2
      h, 6 h, 24 h and 3 days after operation. RESULTS: The plasma EDLS concentrations
      in NYHA IV patients [(403 +/- 27) pg/mL] were significantly higher than those in
      II [(221 +/- 98) pg/mL] and III patients [(296 +/- 71 pg/mL), P < 0.01] before
      CPB. CPB could induce the release of EDLS. The EDLS concentrations in plasma
      increased to (683 +/- 371) pg/mL and (577 +/- 274) pg/mL at 2 h and 6 h
      respectively after CPB, and went back to normal at 24 h after operation. However,
      there was no relationship between plasma EDLS concentration and the time of
      ascending aorta blocked at 2 h or 6 h after operation (r = 0.0748 and 0.0393
      respectively). Over 50% patients in the higher EDLS (> 1000 pg/mL) group are NYHA
      IV, and the ratio was significantly higher than that in lower EDLS group (< 999
      pg/ mL, P < 0.05). There was no difference between higher and lower EDLS groups
      in respect of the requirement of inotropic support and blood pressure.
      CONCLUSIONS: The EDLS release can be induced by heart failure and CPB. The plasma
      EDLS concentrations increase up to climax in 2-6 h after CPB. The higher plasma
      EDLS concentration may improve the cardiac function.

PMID- 18630702
TI  - [Odontoblast-like cell phenotype differentiation of cranial neural crest stem
      cell in vivo].
AB  - OBJECTIVE: To investigate the feasibility of tooth regeneration by seeding
      cranial neural crest stem cell (CNCSC) in vivo. METHODS: Cranial neural tubes,
      dissected from mouse E9 d, were explanted onto fibronectin-coated dishes. CNCSC
      emigrated from the explanted neural tubes, and were cultured in a free-serum
      medium containing modified DMEM/F12. CNCSC, induced by FGF8, BMP2, TGFbeta1 and
      dentin matrix non-collagen protein (DMNCP), were cultured with collagen/chitosan,
      and implanted into the subcutaneous part of immunodeficiency mouse. The
      expression of collagen I/dentin sialophosphoprotein (DSPP) was analyzed by
      immunocytochemistry. RESULTS: With the scaffolds destroying, columnar cells
      possessing polarized nuclei and matrix produced by cells were showed in some
      regions. Immunohistochemical staining demonstrated that collagen type I and DSPP
      were expressed throughout the cytoplasm and matrix produced by cells. CONCLUSION:
      By tissue engineering approach, our experiments further verify the odontoblast
      like cell phenotype differentiation of CNCSC in vivo.

PMID- 18630703
TI  - [Experimental study on the development of tissue-engineered tooth germ with
      heterotopic allotransplantation].
AB  - OBJECTIVE: To compare the growth and development of tissue engineered tooth germ
      implanted into different tissues, and explore a suitable growing environment for
      the tissue engineered teeth in vivo. METHODS: SD rat/porcine tooth germ cells
      from postnatal 4 days were used as seeding cells, which combined various
      scaffolding biomaterials to construct the compound with tissue engineered teeth.
      The allografts were implanted into renal subcapsule, the mesenteries and
      subcutaneous tissues. Then, the implants were retrieved at special time points
      for histological analysis. RESULTS: Further developments were not observed in the
      graft implanted into mesenteries and subcutaneous tissues. Partial grafts were
      fallen off and lost from the subcutaneous tissues after implanted, and there were
      obvious lymphocyte infiltrations in the mesenteries. Moreover, the enamel and
      pulp-dentin complex were observed within the graft implanted in the subrenal
      capsule, which indicated there to be good condition. CONCLUSION: The subrenal
      capsule can provide a promising implantation environment for the further growth
      of allogeneic tissue engineered tooth germ, and the subrenal capsule implantation
      can be used as a new alternative method for tissue-engineering tooth in vivo.

PMID- 18630704
TI  - [Construction of tissue culture model in vitro and investigation of transforming
      growth factor promoting pulp fibroblast to differentiate into the odontoblast].
AB  - OBJECTIVE: To construct the tissue culture model in vitro, and investigate the
      potential of dental pulp fibroblast differentiating into the odontoblast and the
      promoting role of transforming growth factor beta1 (TGF-beta1) on it. METHODS:
      Human pulps were cultured for 3, 7, 14 and 21 days on bone matrix gelatin (BMG)
      in DMEM cultural medium supplemented with TGF-beta1. The characteristics of
      matrix were studied through toluidine blue and Mallory stain. Meanwhile, the
      expression of dentin salivary protein (DSP) on the pulp cells was investigated
      with immunohistochemical staining. RESULTS: This experiment found that the pulp
      tissue in vitro were able to develop into more progressive stage, and some pulp
      fibroblast cells to differentiate into odontoblast-like cells. Toluidine blue and
      Mallory staining analysis revealed the localized deposition of mineralized bone
      dentin matrix that was detected at the site of dental pulp cells.
      Immunohistochemical analysis proved that the DSP synthesized in these cells with
      the presence of TGF-beta1. CONCLUSION: The results demonstrate that this culture
      condition can maintain the phenotype of human pulp tissue. The model of organ
      culture is suitable to study the development of pulp tissue in vitro. TGF-beta1
      can promote the potential of pulp cell into odontoblast, which provides an
      academic basis for tooth repair and regeneration.

PMID- 18630705
TI  - [Spontaneous odontogenic differentiation and critical gene expression of mouse
      dental papilla mesenchymal cell in vitro].
AB  - OBJECTIVE: To observe the spontaneous odontogenic differentiation of mouse dental
      papilla mesenchymal cells in blood serum medium. And to detect the critical gene
      expression of correlated transcription factors what are specific to odontogenic
      and osteogenic differentiation. METHODS: The primary dental papilla mesenchymal
      cells what had been obtained from E16.5 d murine embryo were serially
      subcultivated in the simple serum medium and the serum medium supplemented with
      LIF (leukocyte inhibitory factor) respectively. It was observed whether the
      dental papilla mesenchymal cells differentiated into odontoblast phenotype or
      kept the undifferentiation phenotype. The mRNA expression of specific
      transcription factors were detected in cells with or without odontogenic
      differentiation. RESULTS: The fourth generation and behind of mouse dental
      papilla mesenchymal cells what were cultured in simple serum medium could
      spontaneously differentiate to odontoblast, while the undifferentiation phenotype
      of dental papilla mesenchymal cells could be lasting to ninth generation when
      they cultured in medium supplemented with 10(6) U/L LIF. Whether the dental
      papilla cells differentiate to odontogenic phenotype or not, the members of HOX
      gene family such as Msx1/Msx2, Pax9 and Lhx6/Lhx7 got completely expression.
      These transcription factors were specific to odontogenic mesenchymal cells. Also
      the specific gene of mineralized tissue cells such as DSPP, Sox9, Cbfa1 and Osx
      initiated to express after the odontoblast differentiation. CONCLUSION: Not only
      this spontaneous odontogenic differentiation model of mouse dental papilla
      mesenchymal cells can be the positive control, but also the mode of gene
      expression can provide an evidence for studying how gene changes when adult stem
      cells are induced to odontogenic differentiation.

PMID- 18630706
TI  - [Expression of odontogenic and osteogenic genes in bone marrow mesenchymal stem
      cells with overexpression of mouse dentin sialophosphoprotein].
AB  - OBJECTIVE: To observe the overexpression of dentin sialophosphoprotein (DSPP) in
      mouse bone marrow mesenchymal stem cells (BM-MSC) and the expression of specific
      gene involved in odontogenic and osteogenic differentiation in transfected cells.
      METHODS: Mouse bone marrow mesenchymal stem cells (BM-MSC) were cultured and then
      transfected with DSPP gene by adenovirus-mediated way in vitro. The transfection
      efficiency of DSPP gene was assessed by the marker gene green fluorescent protein
      (GFP). With having observed the morphological transformation of transfected BM
      MSC, we studied whether the transfected BM-MSC would express odontogenic and
      osteogenic genes by RT-PCR. RESULTS: The mouse BM-MSC were obtained and the
      adenovirus mediated DSPP gene used to transfect BM-MSC successfully. The
      transfected efficiency was 42.7%. The transfected BM-MSC were induced to
      differentiate into odontoblast-like cells and meanwhile expressed specific
      odontogenic and osteogenic differentiation genes such as DSPP, DMP1, Msx1/2,
      Pax9, Lhx6/7, Sox9, Cbfa1, Osx, Col I. CONCLUSION: The bone marrow mesenchymal
      stem cells can make differentiation with the overexpression of dentin
      sialophosphoprotein and express specific odontogenic and osteogenic
      differentiation genes.

PMID- 18630707
TI  - [Construction of recombinant adenovirus vector carrying the mouse caveolin-1 in
      gene].
AB  - OBJECTIVE: To construct recombinant adenovirus carrying the mouse dentin caveolin
      1 gene using the recombinant adenoviral vector system AdEasy. METHODS: The cDNA
      fragment of caveolin-1 was derived from pTRE2-caveolin-1 by restriction enzyme
      digestion and subcloned into shuttle plasmid pAdtrack-CMV. The resulting plasmid
      pAdtrack-CMV-caveolin-1, after linearized by digesting with restriction
      endonuclease Pme I, was transformed into E. coli 1 BJ5183 which had been
      transformed by adenoviral backbone plasmid pAdEasy-1. The recombinant plasmid pAd
      caveolin-1 was screened by kanamycin LB plate and then identified by restriction
      enzyme digestion. The linearized adenovirus plasmid pAd-caveolin-1 was packaged
      in 293 cells, then the recombinant adenovirus Ad-caveolin-1 was harvested. The
      expression of green fluorescence protein was observed under fluorescent
      microscope. With further amplification and purification, the titer of recombinant
      adenovirus was determined. RESULTS: The recombinant adenovirus was identified by
      restriction enzyme digestion analysis and gene sequencing. Cytopathic effect and
      the expression of GFP were observed in the infected 293 cells. The sequence of
      caveolin-1 gene insert was the same as that published in the GenBank. The titer
      of the recombinant adenovirus was 2 x 10(9) pfu/mL. CONCLUSION: The mouse
      caveolin-1 recombinant adenovirus was constructed successfully by using AdEasy
      adenovirus system. Cell transfection and expression of exogenous gene can be
      detected directly by observing the expression of GFP. These results provide the
      basis for the further study on the role of caveolin-1 gene in other scopes.

PMID- 18630708
TI  - [Mixed enzyme applied to develop the method on BAlb/c mouse Kupffer cell isolated
      and cultured in vitro].
AB  - OBJECTIVE: To research the reliable method for the isolation and culture of
      Kupffer cell in BALB/c mouse by mixed enzyme. METHODS: Kupffer cells were
      isolated from liver by in situ perfusion and digestion with 0.1% IV collagenase,
      0.2% pronase and 0.01% Dnase I, and by percoll density gradient centrifugation.
      Kupffer cells were identified by fluorescence microscope, immunohistochemistry
      and cell endocytosis effect. RESULTS: Kupffer cells were isolated successfully
      with high purity, the yield of (2-3) 10(6)/per mouse liver and the identification
      that 0.4% trypan blue indicated that the cells survival rate and purity were more
      than 96% and more than 92% respectively. The shape of Kupffer cell appeared to be
      multiplicity, irregularity, polygon and multiangular. Kupffer cells showed
      lysozyme positive by immunohistochemistry staining. And particles of India ink
      were found in cytoplasm. CONCLUSION: Here described technique for isolation and
      culture of Kupffer cells is simple and reliable, and can be used for preparing
      Kupffer cells with high yield, activity and purity.

PMID- 18630709
TI  - [The formation of BPDE-DNA adduct in rat and its determination by high
      performance liquid chromatography].
AB  - OBJECTIVE: To study the benzo (a) pyrene (BaP) induced DNA adduct in rat and
      establish a method to measure the DNA adduct in blood by high performance liquid
      chromatography (HPLC). METHODS: The SD rats were treated with 100 mg/kg of BaP
      DMSO (cosolvent: 1% sodium carboxymethyl cellulose) once by i.p., and the blood
      of femoral vein was collected 5 hours later. The blood DNA was extracted by kit
      and confirmed by agarose gel electrophoresis. After extraction, the DNA adducts
      were hydrolyzed in 0.1 nmol/L HCl at 90 degrees C for 4 hours. The acid
      hydrolysis products (BP-tetrols) of DNA adducts were extracted by ethyl acetate
      and measured by HPLC, and finally confirmed by HPLC-MS. RESULTS: In chromatogram
      there were new peaks to occur for rats treated by BaP, with compared to control.
      By HPLC-MS, one of the new peaks was confirmed to be BP-tetrol. CONCLUSION: The
      rats ingesting BaP in the way described in this experiment can form DNA adducts,
      and the adducts in blood can be detected by HPLC.

PMID- 18630710
TI  - [Influence of cardiac rhythm on image quality of 64-slice multidetector-row CT
      coronary angiography and clinic value of post-processing technology with image].
AB  - OBJECTIVE: To evaluate the influence of cardiac rhythm on 64-slice multi-detector
      row CT coronary angiography and clinic value of imaged post-processing
      technology. METHODS: 687 patients with suspected coronary heart disease who
      underwent 64-slice multi-detector row CT coronary angiography were
      retrospectively analyzed with their CT images. Four group images of patients were
      analyzed and compared according to the fluctuation of cardiac rhythm. Multi-phase
      reconstruction (n = 76) and the ECG-edit software (n = 21) were performed in
      those patients with arrhythmia. RESULTS: The statistical differences were found
      among the imaging quality of each group (chi2 = 225.040, P < 0.001). As the
      fluctuation of cardiac rhythm increased, the quality of CT images dropped down
      concomitantly. After images processed with ECG-edit software, the quality of CT
      coronary angiography images got improved (Z = - 3.385, P = 0.001). In 76 patients
      with multi-phase reconstruction, the image quality of right coronary artery got
      improved in 40% R-R interval when high quality images couldn't be obtained in 75%
      R-R interval (Z = - 4.209, P < 0.001). CONCLUSION: Cardiac rhythm is an important
      factor to affect the CT coronary angiography, but post-processing technology may
      be useful for improving the imaging quality.

PMID- 18630711
TI  - [Time-density curve of 16-slice spiral CT quantitatively distinguishes true from
      false lumen of aortic dissection].
AB  - OBJECTIVE: To use the time-density curves (TDCs) to quantitatively distinguish
      the true from false lumen of aortic dissection (AD). METHODS: 28 cases with AD
      underwent the dynamic scanning of 16-slice spiral computer tomography (SCT). We
      used the CT Dynamic Evaluation software to determine the circulation times of the
      true and false lumens of the AD and got the TDCs, and then analyzed the
      circulation times and CT values of the true and false lumens by using matched t
      test for dependent samples. RESULTS: The TDCs of the true and false lumens of the
      AD were achieved in all 28 patients. The peak CT values [(71.87 +/- 35.14) HU] of
      the true lumen were higher than those [(45.58 +/- 24.00) HU] of false lumen (P <
      0.05); while the time to peak [(23.43 +/- 5.73) s] of the true lumen were earlier
      than that [(29.46 +/- 6.27) s] of false lumen (P < 0.05). The patterns of TDCs of
      the true lumen appeared to be rapid rise followed by rapid decline in 22 cases
      (78.6%) and rapid rise with gradual decline in 6 (21.4%), while the patterns of
      TDCs of the false lumen showed gradual rise followed by gradual decline in 18
      cases (64.3%) and rapid rise with gradual decline in 10 (35.7%). CONCLUSION: The
      TDCs of the true and false lumens showed: the peak CT values of the true lumen
      were higher than those of false lumen; while the time to peak of the true lumen
      were earlier than that of false lumen. So, the time-density curve, is used as an
      original and quantitative method to distinguish the true from false lumen in AD.

PMID- 18630712
TI  - [Preparation of self-microemusifying drug delivery system for volatile oil from
      rhizome of ligusticum Chuanxiong].
AB  - OBJECTIVE: To search on the optimum formula for the seif-microemulsifying drug
      delivery system of volatile oil from rhizome of ligusticum Chuanxiong. METHODS:
      Through solubility experiment, orthogonal screen and drawing phase diagram,
      taking the degree of emulsifying, the volume of the rest oil and emulsion
      particle size as parameters, the appropriate proportion composed of Chuanxiong
      oil, nonionic surfactant and flux was screened for the optimum formulation of
      self-microemulsifying drug delivery system. RESULTS: In the formulation of self
      microemulsifying drug delivery system for volatile oil from rhizome of ligusticum
      Chuanxiong, taking S1 as the nonionic surfactant and C1 as the co-surfactant
      could get the best effect of emulsifying. CONCLUSION: The optimum formula for
      seif-microemulsification of volatile oil from rhizome of ligusticum Chuanxiong is
      volatile oil from rhizome of ligusticum Chuanxiong, S1 and C1, with their
      proportion being 10 : 9 : 1.

PMID- 18630713
TI  - Reframing the diversity question: challenging Eurocentric power hierarchies in
      nursing education.

PMID- 18630715
TI  - Beyond transculturalism: critiques of cultural education in nursing.
AB  - New and innovative educational approaches are needed to prepare a workforce that
      responds to diverse needs of people from a wide variety of cultural backgrounds,
      languages, and worldviews. Despite some movement toward standardization of
      cultural curricular content, there remains a lack of consensus regarding
      pedagogical approaches to cultural education in nursing. An increasing number of
      nurse scholars have identified significant limitations in the process of cultural
      education in nursing and transcultural nursing theory. These critiques reflect a
      schism in the discipline regarding foundational theoretical perspectives and
      conceptualizations of culturally competent health care. This article offers a
      synthesis of transcultural nursing critiques that have appeared in the nursing
      literature over the past decade and explicates the philosophical tensions that
      underlie the varying pedagogical approaches to cultural education in nursing.

PMID- 18630714
TI  - Recruitment and retention of Alaska natives into nursing (RRANN).
AB  - In recognition of the severe underrepresentation of Alaska Natives in the Alaska
      RN workforce, the University of Alaska Anchorage School of Nursing implemented
      Project RRANN (Recruitment and Retention of Alaska Natives into Nursing) to
      recruit Alaska Natives into a nursing career and to facilitate their success in
      the nursing programs. Activities that created connections and facilitated student
      success were implemented. Connection-creating activities included establishing
      community partnerships, sponsoring a dormitory wing, hosting social and
      professionally related events, and offering stipends. Success facilitation
      activities included intensive academic advising, tutoring, and mentoring. The
      effectiveness of Project RRANN is evident in the 66 Alaska Native/American Indian
      students admitted to the clinical major since 1998, when Project RRANN was
      initiated; of those, 70% have completed the major and become licensed, and 23%
      continue to pursue program completion.

PMID- 18630716
TI  - The importance of educational and social backgrounds of diverse students to
      nursing program success.
AB  - This article compares the educational and social backgrounds of Anglo students
      with those of Hispanic/Latino and American Indian students receiving stipends and
      other services from a Nursing Workforce Diversity Grant to determine the possible
      effects of such backgrounds on success in a baccalaureate nursing program.
      Stipend recipients provided baseline background data by interview on admission,
      and the results were compared with corresponding data from a volunteer sample of
      Anglo students to enhance understanding of the educational and social
      circumstances of the stipend recipients and to identify a need for
      individualized, tailored grant approaches. The Hispanic/Latino and American
      Indian students demonstrated less adequate educational backgrounds and lower
      social class as gauged by parental occupation, than did the Anglo students.
      Although overall comprehensive grant strategies maximized the potential for
      success of stipend recipients, strategies need to be tailored to fit each
      individual's unique educational and social background.

PMID- 18630717
TI  - Faculty notions regarding caring in male nursing students.
AB  - Men are entering the field of nursing in increasing numbers. As men enter nursing
      programs, they may encounter role stereotyping and gender bias through the
      faculty's assumption of stereotypical notions of caring. The purpose of this
      interpretive phenomenological study was to describe the ways faculty perceive and
      respond to caring in male nursing students to better understand how to facilitate
      it. The central question for this study was: What are the essences and meaning of
      nursing faculty notions regarding caring in male nursing students? Six faculty
      members in a nursing program with a large percentage of male student enrollment
      were interviewed. Applying a phenomenological data analysis method, the
      researchers identified six themes: altruism, antecedents, attainment, ambiguity,
      agency, and anecdotes. Implications for nursing education and practice are made,
      including the need to recognize, allow, and support male nursing student ways of
      caring.

PMID- 18630718
TI  - Learning about Aboriginal contexts: the reading circle approach.
AB  - As more opportunities arise for nursing students to obtain experience in
      community sites, they will be called on to practice in culturally appropriate
      ways more often. Although nurses remain challenged by the range of populations
      needing differentiated approaches, Aboriginal cultural contexts deserve special
      attention. Nurse educators must help students increase their understanding of
      Aboriginal life and ways of knowing. One way to facilitate this understanding is
      through a learning approach called reading circles. Reading circles offer a
      structure in the classroom for students to interact about ideas or readings. The
      reading circle process is congruent with Aboriginal ways of learning, which
      emphasize working in circle, with each member having a role and an equal chance
      to be heard. Aboriginal students in the class may be particularly comfortable
      with this learning method. This article describes specific steps for
      incorporating the reading circle approach into the nurse education classroom.

PMID- 18630719
TI  - Linguistic and cultural adaptation needs of Mexican American nursing students
      related to multiple-choice tests.
AB  - Hispanic nurses represent less than 2% of the current U.S. nursing workforce,
      despite that approximately 14% of the nation's population is Hispanic. There is
      an urgent need to correct the gross underrepresentation of Mexican Americans, the
      largest subgroup among Hispanics, in the U.S. nursing workforce to provide
      culturally concordant care. One solution is to increase the academic success of
      Mexican American nursing students with English as a second language through
      improved linguistic and cultural adaptation to multiple-choice tests. This
      article will discuss these students' linguistic and cultural adaptation needs
      related to multiple-choice tests and will also present several intervention
      strategies and a case study.

PMID- 18630720
TI  - FIRE UP: tips for engaging student learning.

PMID- 18630721
TI  - New insights in the pathogenesis of aortic aneurysms.
AB  - Aortic aneurysms are an important cause of mortality in the western world.
      Monogenic disorders such as the Marfan syndrome (MFS) are good genetic models for
      the pathogenesis of aortic aneurysm. In the MFS, progressive dilatation of the
      aortic root leads to aortic aneurysm and dissection, often associated with
      precocious death. Early pathogenetic models for MFS focused upon structural
      weakness of the tissues imposed by microfibrillar deficiency. However, recent
      studies of transgenic mouse models have challenged this model and demonstrated a
      central role for the upregulation of the TGFbeta signaling pathway. The discovery
      of a new aortic aneurysm syndrome, the Loeys-Dietz syndrome (LDS), confirmed the
      importance of the cytokine TGFbeta in aneurysm pathogenesis. The main
      distinguishing features between LDS and MFS include the presence of
      hypertelorism, cleft palate/bifid uvula and arterial tortuosity. LDS is caused by
      mutations in the genes encoding the receptors for TGFbeta (TGFBR1/2). This
      insight helped to elucidate the pathogenesis of another rare autosomal recessive
      connective tissue disorder, arterial tortuosity syndrome. This disease is caused
      by mutations in the SLC2A10 gene, coding for GLUT10, a member of the glucose
      transporter family. In analogy to LDS, we demonstrated an upregulation of TGFbeta
      in ATS. Finally, all these insights have also lead to new therapeutic insights.
      In transgenic mouse models it was shown that losartan, an angiotensin II type 1
      receptor with known inhibiting effects on TGFbeta, rescues the aortic phenotype.
      If these promising results are confirmed in human trials, losartan might have
      beneficial effects in the treatment of more common nonhereditary aortic
      aneurysms.

PMID- 18630722
TI  - Therapies aimed at preservation or restoration of beta cell function in type 1
      diabetes.
AB  - Type 1 diabetes is caused by an immune mediated destruction of the insulin
      secreting beta cells in the pancreas. The disease can become clinically apparent
      at any age. At clinical diagnosis, there is invariably some residual beta cell
      function. Recent studies--including one mainly conducted in Belgium--have
      provided proof of principle that short-term humanized anti-T-cell antibody
      treatment is able to preserve residual beta cell function for at least 18 months
      in adult type 1 diabetic patients with a recent clinical onset of disease. The
      effect of anti-T-cell antibody treatment is more pronounced among patients with
      initial higher residual beta-cell function. The resultant stabilizing effect on
      metabolic control is expected to delay chronic complications and avoid
      hypoglycemia in these patients. With a similar goal in mind, non-uremic C-peptide
      negative type 1 diabetic patients are offered beta cell transplantation. During
      the last years the one year survival of these grafts under immune suppression
      with Anti-Thymocyte-Globulin, tacrolimus and mycophenolate mofetil exceeds 80%
      with virtually no cases of primary non-function. Widespread application will
      however only occur if ways are found to induce operational graft tolerance and
      the shortage of viable human donor cells can be overcome. Both islet
      xenotransplantation and stem cell therapy provide possible strategies to solve
      this problem and represent areas of intense investigation. The ultimate goal is
      prevention of clinical disease. Studies by the Belgian Diabetes Registry and
      others in first degree family members of type 1 diabetic patients have refined
      identification of individuals at very high risk of hyperglycemia so that new
      immunological treatments can be tested in the prediabetic phase.

PMID- 18630723
TI  - Ligand and electrically induced acitivation patterns in myenteric neuronal
      networks. Confocal calcium imaging as a bridge between basic and human
      physiology.
AB  - Confocal imaging in combination with fluorescent calcium indicators provides the
      possibility to study neuronal activation in entire neuronal networks. The
      experiments presented in this essay aimed at applying confocal calcium imaging to
      study activation patterns in neuronal networks of myenteric ganglia in situ.
      First we studied the response to electrical train stimulation (ETS). ETS induced
      Ca2+ transients in 52.2% and 65.4% of the neurons when applied orally and
      aborally respectively. We observed more responses during aboral ETS which is not
      in line with the hypothesis of neuronal polarity, suggesting complex neuronal
      activation patterns and neuronal interaction in ETS-induced activation in
      myenteric ganglia. We demonstrated that ghrelin has a direct excitatory effect on
      myenteric neurons in situ via ghrelin receptor activation. Ghrelin induced Ca2+
      transients in one third of the myenteric neurons, involving release of Ca2+ from
      intracellular stores and direct GHS-receptor activation. We found that CRF
      activates one fifth of the myenteric neurons, via CRF1 receptor activation. These
      CRF induced Ca2+ signals involved somatic influx through (mainly R-type) voltage
      operated Ca2+ channels. Finally we set up human studies in healthy volunteers and
      dyspeptic patients to test the effect of ghrelin on gastrointestinal motility.
      Intravenous administration of ghrelin induced a premature phase 3 activity front
      that originated in the stomach and an increase in gastric tone. Ghrelin decreased
      gastric emptying time for fluids and reduced symptom scores for fullness and
      pain. These studies provide further evidence for a role of ghrelin in the
      regulation of gastrointestinal motility, and possibly provide new therapeutic
      approaches. Our studies show that confocal calcium imaging allows to assess
      neuronal activation of myenteric neurons. The influence of new hormones or new
      pharmaceutical compounds on the myenteric plexus can hereby be easily assessed.

PMID- 18630724
TI  - Research on human biological materials and the Council of Europe: some unanswered
      questions, overlaps and empty boxes.

PMID- 18630725
TI  - Conscientious objection in reproductive health care: Analysis of Pichon and
      Sajous v. France.
AB  - This article explores the issue of conscientious objection invoked by health
      professionals in the reproductive and sexual health care context and its impact
      on women's ability to access health services. The right to exercise conscientious
      objection has been recognized by many international and European scholars as
      being derived from the right to freedom of thought, conscience and religion. It
      is not, however, an absolute right. When the exercise of conscientious objection
      conflicts with other human rights and fundamental freedoms, a balance must be
      struck between the right to conscientious objection and other affected rights
      such as the right to respect for private life, the right to equality and non
      discrimination, and the right to receive and impart information. Particularly in
      the reproductive health care context, states that allow health professionals to
      exercise conscientious objection must accommodate this in such a way that its
      exercise does not compromise women's access to health services. This article
      analyses the European Court of Human Rights' decision on admissibility in Pichon
      and Sajous v. France (2001) and argues that a balancing approach should be
      applied in cases of conscientious objection in the sexual and reproductive health
      care context.

PMID- 18630726
TI  - Regulating medical futility: neither excessive patient's autonomy nor physician's
      paternalism.
AB  - In the era of an aging population and escalating healthcare costs, the futility
      debate has become the object of extended critical attention. The issue has
      divided experts in relevant fields into two camps. The proponents of medical
      futility defend the physician's exclusive right to determine the futility of
      treatment and decide whether treatment should be withheld or withdrawn. On the
      other hand, opponents believe that a discourse of power lies at the heart of the
      futility debate. They believe that medical futility was constructed, in part, as
      a means of enhancing the physician's domination in a context wherein medical
      authority was threatened. This paper presents some current approaches to the
      futility debate and highlights positions taken by physicians and bioethicists. It
      concludes that establishing an operational guideline, either at hospital or
      national level, is a critical requirement for resolving problems posed by
      futility. It suggests that policies should not be based on either excessive
      patient's autonomy or physician's paternalism.

PMID- 18630727
TI  - European Court of Justice. ECJ 2008/1 Merck Genericos--Productos Farmaceuticos
      Lda v. Merck & Co. Inc, Merk Sharp & Dohme Lda, 11 September 2007 (C-432/05).

PMID- 18630728
TI  - European Court of Justice. ECJ 2008/2 The Netherlands v. Antroposana and Others,
      20 September 2007 (C-84/06).

PMID- 18630729
TI  - European Court of Justice. ECJ 2008/3 Commission v. Federal Republic of Germany,
      6 December 2007 (Case 456-05).

PMID- 18630730
TI  - European Court of Human Rights. ECHR 2008/1 Case of Kanellopoulou v. Greece, 11
      October 2007, no. 28504/05 (First Section).

PMID- 18630731
TI  - European Court of Human Rights. ECHR 2008/2 Case of Mocarska v. Poland, 6
      November 2007, no. 26917/05 (Fourth Section).

PMID- 18630732
TI  - European Court of Human Rights. ECHR 2008/3 Case of David v. Moldova, 27 November
      2007, no. 41578/05 (Fourth Section).

PMID- 18630733
TI  - European Court of Human Rights. ECHR 2008/4 Case of Pilcic v. Croatia, 17 January
      2008, no. 33138/06 (First Section).

PMID- 18630734
TI  - European Court of Human Rights. ECHR 2008/5 Case of Dodov v. Bulgaria, 17 January
      2008, no. 59548/00 (Fifth Section).

PMID- 18630735
TI  - Council of Europe. Recommendation Rec(2006)7 of the Committee of Ministers to
      member states on management of patient safety and prevention of adverse advents
      in health care.

PMID- 18630736
TI  - Plasma-derived microparticles for biomarker discovery.
AB  - The field of mass spectrometry-based proteomics has been transformed over the
      last decade due to advances in technology, sample preparation, bioinformatics,
      and computational tools. While this has led to a dramatic increase in research
      related to biomarker discovery, the promise of finding a significant number of
      new biomarkers has not yet materialized. Current proteomic technology is able to
      detect and analyze extremely small amounts of proteins (picomole to attomole
      level), but has difficulty detecting and quantifying proteins present at 2- to 3
      orders of magnitude lower than the more abundant proteins. This is referred to as
      the dynamic range problem. Normal biological fluids used for biomarker discovery,
      such as plasma or urine, contain a small number of proteins present at much
      higher amounts than the remaining proteins. For example, in the plasma, albumin
      and immunoglobulins are present at milligrams per milliliter, while proteins of
      interest for biomarker discovery may be present at micrograms to picograms per
      ml. This has led us to investigate the microparticle subproteome which has a high
      likelihood of containing potential biomarkers. While this subproteome makes up
      less than 0.01% of the total plasma proteome, it is rich in proteins altered
      under a variety of pathological conditions.

PMID- 18630737
TI  - Cardiac markers (BNP, NT-pro-BNP, Troponin I, Troponin T, in female amateur
      runners before and up until three days after a marathon.
AB  - PURPOSE: Transient cardiac ventricular dysfunction or sudden cardiac deaths have
      been reported for male athletes participating in marathon racing. Less is known
      about the myocardial response in females. We examined natriuretic peptides and
      cardiac troponins in female athletes after a marathon. METHODS: At the 31st real,
      Berlin Marathon plasma levels of NT-pro-BNP, BNP, cTnI and cTnT were measured in
      15 women (age 35+/-6 years; finishing times between 3:22 h and 5:21 h) at four
      different time points (before, immediately after, day one and day three).
      RESULTS: An increase in [NT-pro-BNP] was observed immediately after the marathon
      (median [NT-pro-BNP] before: 39.6 pg ml(-1), after: 138.6 pg ml(-1), p=0.003)
      with a further increase on day one. [BNP] did not increase immediately after the
      marathon but increased on day one (median [BNP] before: 15 pg ml(-1), day one:
      27.35 pg ml(-1), p=0.006). On day three, [NT-pro-BNP] and [BNP] returned to
      initial values. [cTnI] was under the detection limit prior to the marathon in all
      runners. [cTnT] was under the detection limit before the marathon except in one
      runner who presented a concentration of 0.03 ng ml(-1). Cardiac troponins (median
      [cTnl] after: 0.098 ng ml(-1), p=0.028; median [cTnT] after: 0.032 ng ml(-1),
      p=0.012) increased immediately after the marathon and returned to initial values
      on day one [cTnT] and three [cTnI]. DISCUSSION: Parameters representing cardiac
      stress increased in females after a marathon. Different kinetics of natriuretic
      peptides BNP and NT-pro-BNP post-marathon could be due to their different half
      lives and dependence on renal function. The increase of cTnI and cTnT may result
      from minor myocardial lesions.

PMID- 18630738
TI  - Caffeine monitoring in infants: comparison of automated (VITROS 5, 1 FS)
      chemistry system versus HPLC analysis.
AB  - This is the first study comparing the caffeine testing by HPLC to the MicroTip
      Technology patented by Ortho-Clinical Diagnostics. For the determination of the
      precision for intra-run and day to day variances, control materials with
      concentration ranges between 2.3 microg/mL and 23.3 microg/mL were used. Test
      evaluation was done using plasma samples. The coefficient of variation for intra
      run precision was calculated to range from 4.3% to 2.1%. The coefficients of
      variation for the day-to-day precision were between 4.9% and 2.3%. A coefficient
      of correlation of 0.99% was calculated for the comparison of the two methods. In
      the statistical analysis of the comparison of the methods. Differences between +
      4.5% and - 0.92% could be found. The HPLC system must be ready for use at any
      time necessitating maintenance and increased costs. This, in addition to the low
      sample throughput for caffeine analysis and the findings of this study favour the
      use of an automated clinical chemistry system.

PMID- 18630739
TI  - Polyclonal hypergammaglobulinaemia interference in serum HDL-C assays.

PMID- 18630740
TI  - Oxidized LDL, anti-oxidized LDL and anti-annexin A5 antibodies in primary
      antiphospholipid syndrome.
AB  - The aim of this study was to compare whether oxidized LDL (oxLDL), anti-oxLDL and
      anti-annexin (anx) A5 antibodies are associated with clinical features of primary
      antiphospholipid syndrome (PAPS), and to compare these to well-defined groups of
      non-PAPS myocardial infarction survivors (non-PAPS MI) and to non-PAPS patients
      with pulmonary emboli (non-PAPS PE). All parameters investigated were analyzed by
      ELISA using commercial reagents. PAPS patients with MI, in comparison to the
      group of non-PAPS MI survivors, had significantly elevated concentrations of
      oxLDL (p = 0.003) and anti-oxLDL antibodies (p = 0.024). Anti-anxA5 antibodies of
      the IgG isotype were associated with recurrent abortions (OR = 4.788, p = 0.036,
      95% CI: 1.104 - 20.762). OxLDL and anti-oxLDL antibodies represent additional
      risk factors which, together with other factors, might lead to complications of
      arterial thromboses, such as myocardial infarctions in PAPS, while association of
      IgG anti-anxA5 antibodies with recurrent abortions is a reflection of the small
      number of patients with this feature involved in the study and should therefore
      be investigated further.

PMID- 18630741
TI  - 26 years of external quality controls for the screening of congenital metabolic
      disorders in newborns--a summary of the results.
AB  - The evaluation of the inter-laboratory tests over the 26 year period shows a
      clear improvement in the analysis quality of the test participants. This can be
      clearly seen in the increased recovery rates of the pathological quality control
      samples. Centers are put in the position to adjust their own quality control
      measures for their analysis to international standards, thereby decreasing the
      error rate in their analyses. The introduction of the tandem mass spectrometer
      for newborn screening is inevitably connected to even higher requirements in the
      quality of the measured values. Up to now, though, commercially or scientifically
      determined external quality controls do not exist. In November 2005, as a start,
      we tentatively expanded our (since 1982) existing inter-laboratory controls to
      include parameters determinable by mass spectrometry. A second external control
      will take place in May 2008 for acylcarnitines.

PMID- 18630742
TI  - [Medical ethical aspects].

PMID- 18630743
TI  - Current topics in microbiology and immunology. Nuclear pre-mRNA processing in
      plants. Preface.

PMID- 18630744
TI  - Spliceosomal proteins in plants.
AB  - The spliceosome is a large nuclear structure consisting of dynamically
      interacting RNAs and proteins. This chapter briefly reviews some of the known
      components and their interactions. Large-scale proteomics and gene expression
      studies may be required to unravel the many intricate mechanisms involved in
      splice site recognition and selection.

PMID- 18630745
TI  - Analysis of alternative splicing in plants with bioinformatics tools.
AB  - Alternative splicing is a molecular mechanism utilized by a broad range of
      eukaryotes to extend the repertoire of functions encoded by single genes and to
      posttranscriptionally regulate gene expression. Recent analyses of expressed
      transcript sequences aligned to the complete genomes of Arabidopsis and rice
      indicate that alternative splicing in plants is prevalent and exhibits several
      features similar to other higher eukaryotes including mouse and human. This
      chapter reviews the computational strategies employed to study alternative
      splicing with bioinformatics tools and the recent findings from analyses
      performed on plants by applying such methods.

PMID- 18630746
TI  - Splice site requirements and switches in plants.
AB  - Intron sequences in nuclear pre-mRNAs are excised with either the major U2 snRNA
      dependent spliceosomal pathway or the minor U12 snRNA-dependent spliceosomal
      pathway that exist in most eukaryotic organisms. While the predominant
      dinucleotides bordering each of these types of introns and the catalytic
      mechanism used in their excision are conserved in plants and animals, several
      features aiding in the recognition of plant introns are distinct from those in
      animals and yeast. Along with their short length, high AU content and high
      variation in their 5' and 3' splice sites and branchpoint consensus sequences are
      the most prominent characteristics of plant introns. Detailed surveys of site
      directed mutant introns tested in vivo and chemically induced and naturally
      mutant introns analyzed in planta emphasize the effects of changing individual
      nucleotides in these splice site consensus sequences and highlight a number of
      noncanonical dinucleotides that are functional in plant systems.

PMID- 18630747
TI  - U12-dependent intron splicing in plants.
AB  - U12-dependent (U12) introns have persisted in the genomes of plants since the
      ancestral divergence between plants and metazoans. These introns, which are rare,
      are found in a range of genes that include essential functions in DNA replication
      and RNA metabolism and are implicated in regulating the expression of their host
      genes. U12 introns are removed from pre-mRNAs by a U12 intron-specific
      spliceosome. Although this spliceosome shares many properties with the more
      abundant U2-dependent (U2) intron spliceosome, four of the five small nuclear
      RNAs (snRNAs) required for splicing are different and specific for the unique
      splicing of U12 introns. Evidence in plants so far indicates that splicing
      signals of plant U12 introns and their splicing machinery are similar to U12
      intron splicing in other eukaryotes. In addition to the high conservation of
      splicing signals, plant U12 introns also retain unique characteristic features of
      plant U2 introns, such as UA-richness, which suggests a requirement for plant
      specific components for both the U2 and U12 splicing reaction. This chapter
      compares U12 and U2 splicing and reviews what is known about plant U12 introns
      and their possible role in gene expression.

PMID- 18630748
TI  - Plant SR proteins and their functions.
AB  - SR proteins are a family of splicing factors important for splice site
      recognition and spliceosome assembly. Their ability to bind to RNA and to
      interact with proteins as well identifies them as important players in splice
      site choice and alternative splicing. Plants possess twice as many SR proteins as
      animals, and some of the subfamilies are plant specific. Arabidopsis SR proteins
      are involved in different aspects of plant growth and development as well as in
      responses to environmental cues. The plant-specific subfamilies have been shown
      to be regulated by alternative splicing events, which are highly conserved in
      evolution. The tight regulation of splicing factors by alternative splicing might
      allow coordinated responses of their target genes.

PMID- 18630749
TI  - Spatiotemporal organization of pre-mRNA splicing proteins in plants.
AB  - The general organization ofeukaryotic nuclei, including plant nuclei, into
      functional domains is now widely recognized. Conventional immunocytochemistry and
      visualization of proteins fused to fluorescent proteins (FP) have revealed that
      in plants, RNA and protein components of pre-mRNA splicing are spatially
      organized depending on the stage of cell cycle, development, and the cell's
      physiological state. Application of some of the latest microscopy techniques,
      which reveal biophysical properties such as diffusion and interaction properties
      of proteins, has begun to provide important insights into the functional
      organization of spliceosomal proteins in plants. Although some progress has been
      made in understanding the spatial and temporal organization of splicing machinery
      in plants, the mechanisms that regulate this organization and its functional
      consequences remain unresolved.

PMID- 18630750
TI  - Regulation of splicing by protein phosphorylation.
AB  - Most eukaryotic messenger RNAs are transcribed as precursors that necessitate
      specific and exact processing of intron boundaries. Furthermore, the choice of
      these boundaries appears to be fluid and adaptive to the rate of transcription
      and the developmental and physiological state of the cell. A central regulator of
      splicing reactions and choice are kinases that work through phosphorylation of
      specific factors like RNA polymerase II, which influences the pace of
      transcription and of SR splicing factors. While very different in their
      mechanisms both regulatory pathways will impact on splicing site choice. This
      chapter summarizes the biology of splicing-related phosphorylation activity,
      emphasizing plant-specific aspects in relation to the metazoan counterpart.

PMID- 18630751
TI  - mRNA cap binding proteins: effects on abscisic acid signal transduction, mRNA
      processing, and microarray analyses.
AB  - The plant hormone abscisic acid (ABA) intricately regulates a multitude of
      processes during plant growth and development. Recent studies have established a
      connection between genes participating in various steps of cellular RNA
      metabolism and the ABA signal transduction machinery. In this chapter we focus on
      the plant nuclear mRNA cap binding proteins, CBP20 and CBP80. We summarize and
      report recent findings on their effects on cellular signal transduction networks
      and mRNA processing events. ABA hypersensitive 1 (abh1) harbors a gene disruption
      in the Arabidopsis CBP80 gene. Loss-of-function mutation of ABH1 can also result
      in an early flowering phenotype in the Arabidopsis accession C24. abh1 revealed
      noncoding cis-natural antisense transcripts (cis-NATs) at the CONSTANS locus in
      wild-type plants with elevated cis-NAT expression in the mutant. abh1 also
      revealed an influence on the splicing of the MADS box transcription factor
      Flowering Locus C pre-mRNA, which may result in the regulation of flowering time.
      Furthermore, new experiments analyzing complementation of cpb20 with site
      directed cpb20 mutants provide evidence that the CAP binding activity of CBP20 is
      essential for the observed cbp-associated phenotypes. In conclusion, mutants in
      genes participating in RNA processing provide excellent tools to uncover novel
      molecular mechanisms for the regulation of RNA metabolism and of signal
      transduction networks in wild-type plants.

PMID- 18630752
TI  - Messenger RNA 3' end formation in plants.
AB  - Messenger RNA 3' end formation is an integral step in the process that gives rise
      to mature, translated messenger RNAs in eukaryotes. With this step, a pre
      messenger RNA is processed and polyadenylated, giving rise to a mature mRNA
      bearing the characteristic poly(A) tract. The poly(A) tract is a fundamental
      feature of mRNAs, participating in the process of translation initiation and
      being the focus of control mechanisms that define the lifetime of mRNAs. Thus
      messenger RNA 3' end formation impacts two steps in mRNA biogenesis and function.
      Moreover, mRNA 3' end formation is something of a bridge that integrates numerous
      other steps in mRNA biogenesis and function. While the process is essential for
      the expression of most genes, it is also one that is subject to various forms of
      regulation, such that both quantitative and qualitative aspects of gene
      expression may be modulated via the polyadenylation complex. In this review, the
      current status of understanding of mRNA 3' end formation in plants is discussed.
      In particular, the nature of mRNA 3' ends in plants is reviewed, as are recent
      studies that are beginning to yield insight into the functioning and regulation
      of plant polyadenylation factor subunits.

PMID- 18630753
TI  - State of decay: an update on plant mRNA turnover.
AB  - Proper degradation of plant messenger RNA is crucial for the maintenance of
      cellular and organismal homeostasis, and it must be properly regulated to enable
      rapid adjustments in response to endogenous and external cues. Only a few
      dedicated studies have been done so far to address the fundamental mechanisms of
      mRNA decay in plants, especially as compared with fungal and mammalian model
      systems. Consequently, our systems-level understanding of plant mRNA decay
      remains fairly rudimentary. Nevertheless, a number of serendipitous findings in
      recent years have reasserted the central position of the regulated mRNA decay in
      plant physiology. In addition, the meteoric rise to prominence of the plant small
      RNA field has spawned a renewed interest in the general plant mRNA turnover
      pathways. Combined with the advent of widely accessible microarray platforms,
      these advances allow for a renewed hope of rapid progress in our understanding of
      the fundamental rules governing regulated mRNA degradation in plants. This
      chapter summarizes recent findings in this field.

PMID- 18630754
TI  - Regulation of flowering time by RNA processing.
AB  - Plants control the time at which they flower by integrating environmental cues
      such as day length and temperature with an endogenous program of development.
      Flowering time is a quantitative trait and a model for how precision in gene
      regulation is delivered. In this review, we reveal that flowering time control is
      particularly rich in RNA processing-based gene regulatory phenomena. We review
      those factors which function in conserved RNA processing events like alternative
      3' end formation, splicing, RNA export and miRNA biogenesis and how they affect
      flowering time. Likewise, we review the novel plant-specific RNA-binding proteins
      identified as regulators of flowering time control. In addition, we add to the
      network of flowering time control pathways, information on alternative processing
      of flowering time gene pre-mRNAs. Finally, we describe new approaches to dissect
      the mechanisms which underpin this control.

PMID- 18630755
TI  - Alternative splicing in plant defense.
AB  - Plant resistance proteins directly or indirectly perceive the presence of
      pathogen virulence factors and trigger an effective form of plant immunity that
      often includes programmed host cell death. Because the activation of resistance
      proteins has the potential to be detrimental to the plant, this process is
      tightly regulated on multiple levels. Several resistance genes have been shown to
      be alternatively spliced. Depending on the resistance gene, alternative
      transcripts are thought to limit the expression of R proteins or encode truncated
      R proteins with a positive role in defense activation. In addition, R gene
      alternative splicing is dynamic during the defense response. Possible mechanisms
      of R gene alternative splicing regulation and how alternative R gene transcripts
      fit into the current view of resistance protein-mediated defense responses are
      discussed.

PMID- 18630756
TI  - Nuclear RNA export and its importance in abiotic stress responses of plants.
AB  - Transduction of developmental and environmental cues into the nucleus to induce
      transcription and the export of RNAs to the cytoplasm through the nuclear pore
      complex (NPC) play pivotal roles in regulation of gene expression. The process of
      bulk export of mRNAs from nucleus to cytoplasm is highly conserved across
      eukaryotes. Assembly of export-competent mRNA ribonucleoprotein (mRNP) is coupled
      with both transcription and mRNA processing. The export-competent mRNP consists
      of mRNAs and a dozen nucleocytoplasmic shuttling nuclear proteins, including RNA
      export factors (Mex67-Mtr2 heterodimer, Npl3), poly(A)-binding proteins, DEAD-box
      protein 5 (Dbp5), and nucleoporins (NUPs) in yeast. Mobile NUPs help docking of
      mRNP to the NPC nuclear basket. A partially unfolded mRNP complex appears to be
      pulled through the NPC by using energy from Dbp5-catalyzed ATP hydrolysis. Dbp5
      probably catalyzes the release of mRNA from mRNP in the cytoplasm. In contrast to
      bulk export of mRNAs by a Mex67-Mtr2/Npl3-dependent pathway, a specific subset of
      mRNA export under stress and export of microRNAs are mediated through the
      karyopherin (importin beta) family of proteins in a Ran-GTPase-dependent pathway.
      Our knowledge of mRNA export mechanisms in flowering plants is in its infancy.
      Some proteins of the NUP107-160 complex, NUPs and DEAD-box proteins (DBPs), have
      been studied in flowering plants. Arabidopsis NUP160/SAR1 plays a critical role
      in mRNA export, regulation of flowering, and hormone and abiotic stress
      responses, whereas NUP96/ SAR3/MOS3 is required for mRNA export to modulate
      hormonal and biotic stress responses. DEAD-box proteins have been implicated in
      mRNA export and abiotic stress response of yeast and higher plants. Arabidopsis
      DBP CRYOPHYTE/LOS4 plays an important role in mRNA export, abiotic stress
      response, germination, and plant development. Further studies on various
      components of nuclear mRNA export in plants during nonstress and stress
      conditions will be necessary to understand the link between mRNA export and
      stress-responsive gene expression.

PMID- 18630757
TI  - Regulation of alternative splicing of pre-mRNAs by stresses.
AB  - A substantial fraction (approximately 30%) of plant genes is alternatively
      spliced, but how alternative splicing is regulated remains unknown. Many plant
      genes undergo alternative splicing in response to a variety of stresses. Large
      scale computational analyses and experimental approaches focused on select genes
      are beginning to reveal that alternative splicing constitutes an integral part of
      gene regulation in stress responses. Based on the studies discussed in this
      chapter, it appears that alternative splicing generates transcriptome/proteome
      complexity that is likely to be important for stress adaptation. However, the
      signaling pathways that relay stress conditions to splicing machinery and if and
      how the alternative spliced products confer adaptive advantages to plants are
      poorly understood.

PMID- 18630758
TI  - Intron-mediated regulation of gene expression.
AB  - Introns can significantly affect gene expression in plants and many other
      eukaryotes in a variety of ways. Several types of gene regulation, both positive
      and negative, that involve plant introns are reviewed in this chapter. Some
      introns contain enhancer elements or alternative promoters, while many others
      elevate mRNA accumulation by a different process that has been named intron
      mediated enhancement (IME). The introns involved in IME must be within
      transcribed sequences near the start of a gene and in their natural orientation
      to increase expression. The intron sequences involved are still poorly defined,
      and the mechanism of IME remains mysterious. A model of IME is presented in which
      introns increase transcript elongation.

PMID- 18630759
TI  - The role of the plant nucleolus in pre-mRNA processing.
AB  - The nucleolus is a multifunctional compartment of the eukaryotic nucleus. Besides
      its well-recognised role in transcription and processing of ribosomal RNA and the
      assembly of ribosomal subunits, the nucleolus has functions in the processing and
      assembly of a variety of RNPs and is involved in cell cycle control and
      senescence and as a sensor of stress. Historically, nucleoli have been tenuously
      linked to the biogenesis and, in particular, export of mRNAs in yeast and
      mammalian cells. Recently, data from plants have extended the functions in which
      the plant nucleolus is involved to include transcriptional gene silencing as well
      as mRNA surveillance and nonsense-mediated decay, and mRNA export. The nucleolus
      in plants may therefore have important roles in the biogenesis and quality
      control of mRNAs.

PMID- 18630760
TI  - A day of anesthesia in Lebanon: years of strife hone skills for trauma
      anesthesia.

PMID- 18630761
TI  - Awareness during anesthesia--an update.

PMID- 18630762
TI  - Arteriovenous malformation, complications, and perioperative anesthetic
      management.
AB  - Arteriovenous malformations (AVMs) are the most common intracranial vascular
      malformation, with an estimated occurrence of 1:5000-1:2000 persons. The repair
      requires careful embolization, often followed by stereotactic radiosurgery and
      can also include open craniotomy. Preoperatively, patients may be healthy or
      dramatically unstable, as 30-50% of these cases present with acute cerebral
      hemorrhage. One of the most important considerations for the anesthesiologist
      should be attempting to achieve hemodynamic stability in the face of potential
      increased intracranial pressure and subsequent vulnerability of the tissues to
      ischemic insult. Knowledge of the risks and hazards of the procedure and
      collaboration with specialists, including neuroradiologists, critical care
      physicians, and potentially neurosurgeons, ultimately form the basis for
      appropriate management. AVM's can lead to potentially fatal ischemic or
      hemorrhagic complications that may occur in up to 8% of cases. The protection of
      the airway, adequate monitoring, and maintaining cardiovascular and neurological
      stability, are critical. Further, in the setting of a radiological suite,
      peripheral location considerations involving equipment, monitors, and appropriate
      drugs and sustaining the patient's immobility during the radiological procedures,
      while managing potential perioperative complications are all essential.

PMID- 18630763
TI  - Pain relief following thoracoscopic sympathectomy for palmar hyperhidrosis: a
      prospective randomised double-blind study.
AB  - BACKGROUND: Acute pain management following thoracoscopic sympathectomy (TS) has
      been described in the literature. The combination of interpleural (IP) injection
      of bupivacaine and intramuscular injection. (I.M) NSAIDs has not been reported.
      Therefore we conducted this randomized controlled trial to compare this technique
      to other reported techniques described for postoperative analgesia following TS.
      METHODS: 40 patients scheduled to have TS under general anesthesia for the
      treatment of hyperhidrosis were randomly allocated into 4 groups. Group 1
      received 1.5 mg/kg b.w I.M pethidine at end of surgery. Group 2 received
      ketoprofen 100 mg I.M at end of surgery. Group 3 received 0.4 ml/kg b.w
      interpleural bupivacaine 0.5%. Group 4 received a combination of I.M ketoprofen
      (100 mg) in addition to interpleural bupivacaine (0.4 ml/kg). Postoperative pain
      was assessed using the 11- point numeric rating score (NRS) at 7 different
      intervals. First, immediately on admission to PACU, every 2 hours for the next 8
      hours then at 12 and at 24 hours. Pain was assessed at rest, during deep
      inspiration and while coughing. ANOVA was used for statistical analysis and Chi
      square test for comparing of the data where P values <0.05 were considered
      significant. RESULTS: The NRS at rest was 3.2 (1.9), 2.4 (1.6), 3 (1.9) and 0.7
      (0.9) at Groups 1, 2, 3 and 4 respectively with significant difference in Group 4
      versus other Group (P < 0.05) at 2 hours postoperatively and up to 24 hours
      postoperatively. The same trend was also found during maximal inspiration and
      while coughing. Opioid consumption in 24 hours was significantly reduced in Group
      4 compared to other Groups. CONCLUSIONS: Combination of IP bupivacaine and I.M
      ketoprofen provided superior analgesia when compared to each modality alone and
      was better than intramuscular pethidine injection in terms of NRS and the
      consumption of rescue morphine postoperatively. Further studies are needed on
      large sample size to confirm our results.

PMID- 18630764
TI  - Post-thoracotomy pain and pulmonary function--comparison of intermittent
      intercostal bupivacaine vs intravenous pethidine.
AB  - OBJECTIVE AND METHODS: In a prospective, observer-blind study, 50 patients
      scheduled for posterolateral thoracotomy were investigated to compare the effects
      of intermittent intercostal extrapleural bupivacaine (n = 25) and intravenous
      pethidine (n = 25) on post-thoracotomy pain and pulmonary function. The severity
      of chest pain (objectified by the use 5-point scale of Prince Henry) and changes
      in spirometric values [forced vital capacity (FVC), forced expired volume in 1 s
      (FEV1) and FEV1/FVC] were monitored during the first three postoperative days.
      Because intravenous pethidine was used to supplement pain relief in the patients
      who received intercostal analgesia, total pethidine used was compared to that
      administered to patients in the intravenous pethidine group. RESULTS: There were
      no statistical significant differences regarding patient demographics in both
      groups. No complications occurred. There was no significant difference between
      mean pain scores in the first postoperative day, but in the second and third
      postoperative days and also in the whole first 72 post-operative hours, pain
      scores were significantly higher in the intravenous group than the intercostal
      group. The postoperative decrease in FVC and FEV1 was significantly less with
      intercostal bupivacaine compared with the intravenous pethidine. There was no
      significant intergroup difference in the post- to pre-operative FEV1/FVC ratio.
      The total amount of the pethidine received by the patients was significantly
      higher in the intravenous group than the intercostal group. CONCLUSION:
      Intermittent intercostal nerve block with bupivacaine appears to be a promising,
      safe and reliable technique in the management of post-thoracotomy pain. Use of
      intercostal bupivacaine could significantly reduce or even eliminate the
      postoperative need for systemic narcotics.

PMID- 18630765
TI  - Opioid sparing effect of epidural levobupivacaine on postoperative pain treatment
      in major spinal surgery.
AB  - BACKGROUND AND OBJECTIVE: Continuous epidural administration of a local
      anesthetic drug for postoperative pain treatment of patients, who undergo a
      fusion operation of lumbar vertebrae is limited by the suction of wound drainage.
      The effect of the single epidural administration of levobupivacaine 0.25% 10 mL
      20 minutes before finishing of skin closure was examined on the postoperative
      demand for piritramide. METHODS: The study was conducted in a prospective, single
      blind and randomized manner. Forty patients scheduled for posterior
      intervertebral body fusion of two or three vertebrae were divided into two
      groups. Group A received levobupivacaine 0.25% 10 mL epidurally, Group B received
      piritramide 0.08 mg kg(-1) i.v. Time of administration was 20 minutes before
      predicted finish of skin closure in both groups. Piritramide was administered
      intravenously to achieve a VAS of 3 or less during the phase of awakening. After
      regaining of co-operativity, piritramide was self administered via PCA pump. VAS
      and the demand of piritramide within 12 hours postoperative were recorded.
      RESULTS: VAS at the time of being approachable (P = 0.23), VAS at the time of
      regaining co-operativity (P = 0.53) and VAS 12 hours postoperative (P = 0.27) did
      not differ significantly. The postoperative demand of piritramide was
      significantly lower in Group A (0.36 +/- 0.25 mg kg(-1) vs. 0.52 +/- 0.19 mg kg(
      1) in Group B) (P = 0.026). CONCLUSION: The epidural administration of
      levobupivacaine 0.25% 10 mL 20 minutes before finishing of skin closure effects
      opioid sparing in the pain treatment of patients undergoing posterior interbody
      fusion of two or three vertebrae.

PMID- 18630766
TI  - Opioid saving strategy: bilateral single-site thoracic paravertebral block in
      right lobe donor hepatectomy.
AB  - BACKGROUND AND OBJECTIVES: Postoperative analgesia after hepatectomy remains a
      challenge, mainly because of limited therapeutic index of the conventional
      opioids. The aim of this study is to evaluate the efficacy of bilateral single
      site thoracic paravertebral block for the management of postoperative pain
      following right lobe donor hepatectomy (RLDH) using a prospective, randomized and
      controlled study design. METHODS: Twenty four adult patients, aged 18-50 years,
      ASA-I-II, of both sexes scheduled for right lobe donor hepatic resection, were
      enrolled in this study. Patients were randomly allocated into 2 equal groups of
      12 patients each. Before induction of general anesthesia, all patients received
      bilateral single-site thoracic paravertebral injection at the level of T7-8 in
      the sitting position. Patients of Group B were injected with 25 mL of bupivacaine
      0.25% with epinephrine 1:200.000 on each side. Patients of Group P were injected
      with 25 mL of 0.9% NaCl (placebo). General anesthesia was standardized in all
      patients. Postoperative pain score, analgesic requirements and the incidence of
      postoperative nausea and vomiting were recorded. RESULTS: Bilateral single-site
      thoracic paravertebral block significantly decrease the pain visual analogue
      score parameters. Total morphine consumption in the first 24 hours
      postoperatively was decreased by more than 50% in Group B (21.76 +/- 6.8 mg
      compared to 44.12 +/- 9.2 mg in Group P). There was significant prolongation in
      time to rescue analgesia (104.08 +/- 2.04 min in Group B, and 31.5 +/- 6.14 min
      in Group P). Postoperative nausea and vomiting was significantly less in the
      active Group B when compared to the controlled Group P. CONCLUSION: Bilateral
      single-site thoracic paravertebral block is easy, safe and efficient technique
      for postoperative pain management in patients undergoing right lobe donor
      hepatectomy.

PMID- 18630767
TI  - Tracheostomy under jet-ventilation--an alternative approach to ventilating
      patients undergoing surgically created or percutaneous dilational tracheostomy.
AB  - In a prospective observational study we compared the results of 297 elective
      tracheostomies under jet-ventilation with regard to its complication rate and
      practicability. Of those, 156 patients underwent surgically created tracheostomy
      (SCT) and 141 patients percutaneous dilational tracheostomy (PDT). Initially, in
      159 patients jet-ventilation was performed using a jet-cannula inserted
      intratracheally through the cricothyroid membrane. In the remaining 138 patients
      the jet-ventilator was connected to the endoscopic instrument channel (2.2 mm ID,
      4.9 mm OD, 600 mm Length) and ventilation via the fiberoptic bronchoscope (FB
      15x, Pentax Europe GmbH, Hamburg) was applied manually. With jet-ventilation,
      oxygenation was maintained throughout the procedure as long as the tracheal
      puncture was successful und jet-cannula fixed in place. The bronchoscope-guided
      gas stream, when compared to jet-cannula inserted intratracheally, offered more
      space for tracheostomy and safety for the patient. The permanent danger of
      mishappenings and dislocation involved with the jet-cannula could be avoided,
      since the bronchoscope was operating on under direct visualization. Under these
      circumstances, PDT is an acceptable approach to inserting a tracheostomy tube
      under jet-ventilation via bronchoscope, particularly for the management of
      difficult airway in critically ill patients.

PMID- 18630768
TI  - Effect of bispectral index (BIS) monitoring on postoperative recovery and
      sevoflurane consumption among morbidly obese patients undergoing laparoscopic
      gastric banding.
AB  - Early and uneventful postoperative recovery of morbidly obese patients remains a
      challenge for anesthesiologists. It could be valuable to titrate the
      administration of inhaled anesthetic, such as sevoflurane, in morbid obese
      patients, in order to shorten emergence using bispectral index (BIS) monitoring.
      It would be a great advantage if BIS permitted a more rapid recovery and less
      consumption in morbidly obese patients with a high cost inhaled agent. The aim of
      the study is to show whether the titration of sevoflurane based on the BIS
      monitoring would allow shortening of recovery time in morbidly obese patients and
      to evaluate whether BIS monitoring would contribute to reduce the amount of
      sevoflurane administered while providing an adequate anesthesia. PATIENTS AND
      METHODS: Thirty morbidly obese ASA I & II patients undergoing laparoscopic
      gastric banding (LAGB) procedures were studied. In the first group (15 patients),
      patients were anesthetized without the use of BIS (non BIS or control group), and
      sevoflurane being administered according to standard clinical practice (control
      group). In the second group (15 patients), sevoflurane was titrated to maintain a
      BIS value between 40 and 60 during surgery, and then 60-70 during 15 min prior to
      the end of surgery (BIS group). Recovery times were recorded. Time to extubation
      was also noted, as well as the time to achieve a modified Aldrete score of 9 were
      evaluated subsequently at 10-min intervals until 3 h after surgery by nurses who
      had no knowledge of the study. Sevoflurane consumption was calculated using the
      vaporizer weighing method. RESULTS: Awakening and extubation times were
      significantly shorter in the BIS group (P < 0.05). In the BIS (vs. non BIS)
      group, there were no significant differences observed in the time to obtain an
      Aldrete score of 9. The sevoflurane consumption and cost in the BIS group were
      lower than in the non BIS group (P < 0.05). CONCLUSION: Bispectral index
      monitoring during anesthesia for morbidly obese patients provides statistically
      significant reduction in recovery times. It also has the added advantage in
      decreasing sevoflurane consumption.

PMID- 18630769
TI  - Neuromuscular effects of cisatracurium in morbidly obese patients.
AB  - Obesity is associated with significant changes in body composition and function
      that may alter the pharmacodynamics and pharmacokinetics of various drugs. In
      this study, we investigated the neuromuscular effects of cisatracurium in
      morbidly obese as compared to control group of normal body weight patients. In
      the morbidly obese group (n = 20), corrected weight was used to calculate the
      drug doses. In the control group (n = 20), the dose was calculated on ideal body
      weight (IBW). 0.15 mg/kg(-1) cisatracurium was administered as the neuromuscular
      blocker. Neuromuscular effects were recorded at T0 (onset time), T1 (appearance
      of first stimulus of TOF), T25 (25% recovery of T1) and T25-75 (time of T25 to
      T75, recovery time). T0 was determined as 177 +/- 23 s and 168 +/- 19 s in the
      morbidly obese, and control group, respectively. T25 was determined as 46 +/- 7
      min and 56 +/- 8 min, in the morbidly obese and control group, respectively (p <
      0.05). T25-75 was determined as 11 +/- 5 min and 14 +/- 6 min in the morbidly
      obese and control group, respectively (p < 0.05). Intubation conditions were
      determined as good in 13, excellent in 7 patients in the morbidly obese group,
      and as good in 4 and excellent in 16 patients in the control group (p < 0.05). As
      different neuromuscular effects of cisatracurium were detected, we conclude that
      ne uromuscular agents must be monitored in the morbidly obese patients.

PMID- 18630770
TI  - Adriamycin induced pulseless electrical activity and cardiovascular collapse
      during general anesthesia for ventriculo-peritoneal shunt insertion. A case
      report.
AB  - We report a case of a 45-year-old female undergoing an emergency
      ventriculoperitoneal shunt surgery. The patient had brain metastatic lesions of
      breast carcinoma with associated hydrocephalus. She had received Adriamycin as a
      part of chemotherapy regimen for breast cancer. Her preoperative cardiovascular
      status was normal. Under general anesthesia, the patient had a sudden
      cardiovascular collapse. The patient had a pulseless electrical activity and
      required inotropic support for cardiovascular stability. The possible cause is
      discussed.

PMID- 18630771
TI  - Anesthesia for third ventriculostomy. A report of 128 cases.
AB  - BACKGROUND: Endoscopic third ventriculostomy (ETV) has become the standard
      surgical procedure for treatment of non-communicating hydrocephalus. The aim of
      this study is to report our results over the past ten years with reference to
      perioperative complications of ETV with a review of some specific anesthetic
      issues. METHODS: The computerized database (in the Department of Neurosurgery)
      and the medical records of 128 patients who underwent ETV between February 1998
      and February 2007 at our Hospital, were reviewed. Data collected were, age, sex,
      weight, height, preoperative biochemical analysis, duration of the procedure,
      anesthetic drugs used, amount of irrigation fluid used, blood loss, postoperative
      biochemical analysis and perioperative complications. RESULTS: Preoperative
      biochemical analysis for all patients was within normal ranges. Normal saline
      0.9% was used as irrigation fluid for all patients. The volume during the
      procedure used ranged from 2 to 6 L (mean 3 L). When correlating postoperative
      serum sodium mean values to the volume of irrigation fluid used, it showed non
      significant correlation (r= 0.07). Serum potassium level has shown significant
      decrease postoperatively compared to preoperative levels (P < 0.05). The other
      biochemical analysis parameters showed non-significant changes postoperatively
      compared to preoperative data (P > 0.05). CONCLUSION: Anesthesiologists should be
      aware of the intra and postoperative complications secondary to ETV.
      Intraoperative bradycardia is the commonest arrhythmia occuring during the
      procedure. Precautions, like alerting the surgeon and pulling out the scope, are
      enough to revert bradycardia if it occurs. Though postoperative electrolyte
      imbalance occurs we believe it has no clinical significance. We believe that
      either normal saline or lactated Ringer solutions could be safely used for
      intraoperative irrigation with minimal postoperative impact. Though the procedure
      is a minimally invasive procedure, close observation of vital signs, serum
      electrolytes as well as volume and temperature of the irrigation fluid and close
      communication between anesthesiologist and surgeon, are prerequisites for better
      outcome.

PMID- 18630772
TI  - The effect of intravenous nitroglycerine on blood pressure during intubation.
AB  - OBJECTIVES: Hypertension is one of the most frequent complication during
      laryngoscopy and intubation; thus in the premedication or induction stages, many
      drugs have been used to control this hypertension. Nitroglycerine is one of the
      drugs thought to be effective and the purpose of this study is to appraise this
      deliberation. METHODS: 150 patients of 20-50 years of age were enrolled in this
      randomized double blind clinical trial. They were randomly divided into two
      group, one received 2 microg/kg nitroglycerine while the other group did not
      received any drug. Blood pressure was checked in 3 different stages and compared.
      RESULTS: In both groups, pre and post intubation systolic pressure had a
      significant difference; whereas this relation could not be found for the
      diastolic pressure. These variables did not have a statistically significant
      relation prior to intubation; whilst after intubation, a significant relation was
      elicited. CONCLUSION: Injection of 2 microg/kg nitroglycerine immediately after
      anesthetic induction is effective in preventing the unwanted increase in the
      blood pressure, and as a result, complications following this response in
      patients with ischemic heart disease would be reduced.

PMID- 18630773
TI  - Fluid resuscitation of acute hemorrhage in uninephrectomized rabbits--effects on
      the early function of the remnant kidney.
AB  - The aim of this study was to determine the effects of fluid resuscitation of
      acute hemorrhage on the early function and histopathology of the remnant kidney
      in uninephrectomized rabbits. Thirty-nine adult rabbits were studied in four
      groups. Group 1 (n = 8) included healthy controls; Group 2 (n = 10) healthy, bled
      animals; Group 3 (n = 10) uninephrectomized, non-bled animals; and Group 4 (n =
      11) uninephrectomized, bled animals. In the hemorrhage groups, 8 mL kg(-1) of
      blood was drawn, and replaced with lactated Ringer's solution three times the
      volume of shed blood. Urine and blood samples were collected after 120-minutes of
      observation. None of the animals experienced hypotension during the study period.
      Serum and urinary electrolytes were similar between the Groups (p > 0.05). Urine
      output was lower in Groups 3 and 4 than in Group 1 (p = 0.001, both). Urinary
      microalbumin, NAG, fractional sodium excretion and creatinine clearance were
      similar in all four Groups. Light microscopic evaluation revealed only slight
      enlargement of the proximal tubule lumen in the renal medulla of the rabbits that
      were both uninephrectomized and bled. We observed no deleterious effects of well
      resuscitated hemorrhage on early function and histopathology of the remnant
      kidney in uninephrectomized rabbits.

PMID- 18630774
TI  - Caffeine in children with obstructive sleep apnea.
AB  - BACKGROUND: Children with obstructive sleep apnea (OSA) have a higher rate of
      adverse post-extubation respiratory events, such as laryngospasm, upper airway
      obstruction, apnea, desaturation and/or need for re-intubation. They are overly
      sensitive to sedatives and narcotics. Although the etiology of OSA is primarily
      obstruction (mechanical or neuromuscular), a central element may contribute to
      OSA. Caffeine citrate has been shown to be effective in treating apnea of
      prematurity. This study evaluated whether the administration of caffeine benzoate
      to children with OSA decreases the number of children who experience adverse post
      extubation respiratory events. METHODS: In a randomized, double-blind and placebo
      controlled study, children with OSA scheduled for adenotonsillectomy (T&A)
      received either caffeine benzoate, 20 mg/kg IV, (caffeine group, n = 36) or
      saline (placebo group, n = 36). The primary outcome evaluated the number of
      children who developed adverse post-extubation respiratory events, and the
      secondary outcome was the incidence of those events. RESULTS: The results
      demonstrated the two groups differed in the number of children who developed
      adverse post-extubation respiratory events (p = 0.032). The overall incidence of
      adverse postoperative respiratory events was less in the caffeine group than the
      placebo group (p = 0.0196). CONCLUSION: In children with OSA scheduled for T&A,
      administration of caffeine benzoate, 20 mg/kg IV, decreased the number of
      children who developed adverse post-extubation respiratory events and decreased
      the overall incidence of adverse post-extubation respiratory events. PACU
      duration, hospital discharge time and postoperative delirium did not differ
      between groups.

PMID- 18630775
TI  - Transient severe left ventricular diastolic dysfunction during intraoperative
      transesophageal echocardiography--a case report.
AB  - A 55-year-old man with significant lesion of left anterior descending artery and
      left ventricular systolic dysfunction, became candidate for coronary artery
      bypass grafts surgery. Intraoperative transesophageal echocardiography (TEE) was
      done for evaluation of severity of mitral regurgitation. During surgery,
      suddently systolic blood pressure dropped to 50 mmHg and lasted for 2 minutes and
      grade III left ventricular (LV) diastolic dysfunction occurred. After restoring
      blood pressure to 110/60 mmHg, LV diastolic pattern returned to baseline pattern.
      The decreased coronary perfusion pressure and its effect on diastolic function
      may be responsible for this pattern of diastolic dysfunction.

PMID- 18630776
TI  - Anesthesia for a patient with Wilson's disease--a case report.

PMID- 18630777
TI  - A rare cause of endotracheal tube obstruction: a broken stylet going unnoticed--a
      case report.

PMID- 18630778
TI  - Surgical removal of a looped and knotted epidural catheter in a postpartum
      patient--a case report.
AB  - We report a case of unsuccessful removal of an epidural catheter in a postpartum
      patient following a labour epidural analgesia, which ultimately required surgical
      intervention and fenestration ligamentum flavum to remove the epidural catheter.
      A 26 year old, requested an epidural analgesia for her labour pain. The epidural
      catheter was inserted under aseptic technique, and she was comfortable throughout
      her labour and had a normal vaginal delivery 4 hours later. One hour later, the
      acute pain nurse tried to remove the epidural catheter and encountered
      difficulty, she reported this to the resident on call, who also tried and found
      it unusually difficult to remove. A senior consultant was involved where he found
      a high resistance, several methods had been tried unsuccessfully. Surgical
      removal was the option, patient and partner were informed and consented, a
      neurosurgeon was consulted. Through a small incision (1 inch) a fenestration of
      ligamentum flavum was performed and a knotted and looped epidural catheter was
      removed. Patient was discharged next day, and in the follow up and subsequent
      visits patient remained well with no other complaints.

PMID- 18630779
TI  - All good things must come to an end.

PMID- 18630780
TI  - Training for interdisciplinary health research: defining the required
      competencies.
AB  - Although interdisciplinary research is becoming the dominant model for
      understanding complex health issues, little is known about the competencies
      required for successful interdisciplinary collaboration. Published research has
      discussed attitudes about interdisciplinary work and organizational resources but
      not the needed competencies. This report describes the method and results of the
      competency specification process for health research. Based on an established
      definition of interdisciplinary research, a preliminary set of competencies was
      developed from expert opinion of key informants and a review of the
      interdisciplinary research literature. A Delphi panel of interdisciplinary
      researchers then reached consensus on 17 competencies necessary for
      interdisciplinary research.

PMID- 18630781
TI  - Impact of an interprofessional community-based educational experience on
      students' perceptions of other health professions and older adults.
AB  - Caring for older adults has become increasingly complex due to multiple health
      and societal factors. The purpose of this study was to evaluate the impact of an
      interprofessional community-based educational project on students' attitudes
      toward other health care professions and older adults. A pretest and posttest
      quasi-experimental research design was implemented with 64 participating students
      from four health care professions (nursing, occupational therapy, physical
      therapy, and pharmacy). These students completed the Interdisciplinary Education
      Perception Scale (IEPS) and Survey of Attitudes on Aging Scale (SAAS) before and
      following an educational experience with older adults. Qualitative data were
      collected through student reflection journals and focus groups with participating
      students. The results of the study showed that interprofessional community-based
      learning had a significant impact on some students' attitudes toward older
      adults. The difference between pretest and posttest reached a statistically
      significant level on the SAAS in occupational therapy (p = 0.013) and physical
      therapy students (p = 0.044). No significant differences, however, were found
      between the pretest and posttest in pharmacy (p = 0.097) or nursing students (p =
      0.144). Similarly, the experience also had a positive impact on some students'
      perceptions of other health care professions as measured by the IEPS. A
      significant difference was found between the pretest and posttest in occupational
      therapy (p = 0.000) and physical therapy students (p = 0.028). This study
      indicates that interprofessional community-based learning can be an effective
      method for some students to increase their understanding and respect toward other
      health professionals and older adults.

PMID- 18630782
TI  - Assumptions lead to the devaluation of dietitian roles in long-term care practice
      environments.
AB  - Changing demographics in aging place new demands on dieticians related to
      education and subsequent employment. This study presents data from a survey
      illuminating dietitians' perceptions concerning the acquisition of entry-level
      clinical competence within a single practice setting. A purposive sample
      consisting of recent, employed internship graduates (n = 8) and internship
      supervisors (n = 6) from both long-term and active care settings completed a
      survey and was interviewed. While initial analysis suggested there were perceived
      risks and benefits associated with receiving clinical training exclusively in
      either of the environments, a more disturbing finding was a pervasive attitude
      indicating long-term care dietitian roles and training were devaluated. Thematic
      analysis indicated that issues related to career commitment, skill development,
      and philosophy of care were barriers to viewing training or working in long-term
      care as comparable to training or working in active care environments. Attitudes
      expressed were based on assumptions that could be clarified through increased
      education and communication, leading to a greater understanding of dietitian
      roles. Individual and professional efforts must be directed at creating a
      professional culture that fosters the valuing of all practice areas and the
      recognition of unique, rather than inferior, skills, knowledge, attitudes, and
      behaviors that support those environments.

PMID- 18630783
TI  - Barriers to and opportunities for the implementation of best practice
      recommendations in chiropractic: report of a focus group.
AB  - The objective of this study was to describe the perspectives of stakeholders in
      leadership positions within the chiropractic profession regarding implementation
      of best practice guidelines. Eight individuals involved in leadership positions
      within the chiropractic profession participated. The setting was a single 2-hour
      meeting held at a national chiropractic research/educational conference. Our
      findings suggest that delivery capacity can be strengthened if the system as a
      whole is taken into consideration and a multifaceted strategy is used for the
      dissemination and implementation of the best practice recommendations. The
      perspectives of stakeholders in leadership positions in chiropractic about the
      implementation of best practice recommendations are presented. The data generated
      from the focus group will guide the development of an implementation strategy for
      best practices for the chiropractic profession. Lessons learned may benefit the
      broader complementary and alternative medicine community.

PMID- 18630784
TI  - Using self-determination theory to describe the academic motivation of allied
      health professional-level college students.
AB  - This study investigated the various reasons that allied health students believe
      they are currently attending college. The Academic Motivation Scale was
      administered to a convenience sample of 222 upperclassmen and graduate-level
      students (162 women, 46 men). The Academic Motivation Scale proposes various
      reasons for continued engagement in academic pursuits that may be characteristic
      of personal and current reasons for persistence in a subject's particular
      academic program. The results showed that students portrayed themselves as
      currently attending college for both intrinsically and extrinsically motivated
      reasons. The most frequently endorsed motivational styles were identified
      (autonomous) extrinsic motivation and externally regulated (nonautonomous)
      extrinsic motivation. This study showed that this sample of professional-level
      college students was not completely self-determined in their end-stage academic
      pursuits. One conclusion that may be drawn from this study is that allied health
      programs that provide students with an educational context that supports self
      determination may encourage future allied health professionals to develop the
      ability to support the self-determination of their future clients.

PMID- 18630785
TI  - Retrospective analysis of the behavioral interview and other preadmission
      variables to predict licensure examination outcomes in physical therapy.
AB  - Evidence supporting the use of personal interviews in admissions decisions for
      health professions programs is conflicting. This retrospective study was intended
      to (1) quantify interrater reliability for assessing performance on a particular
      type of structured interview, the behavioral interview, and (2) examine the
      ability of multiple preadmission variables, including performance on the
      behavioral interview, to predict first-time performance on the national physical
      therapy licensing examination (NPTE). Data from 89 interviewees during the 2006
      07 admissions cycle were used to examine inter-rater reliability. Data from 141
      students who graduated from 2001 to 2005 were used to examine predictive validity
      of multiple preadmission variables on NPTE performance, including undergraduate
      cumulative grade point average (GPA), preprofessional science GPA, performance on
      the Graduate Record Examination (GRE) (including its analytical, quantitative,
      and verbal subscales), and performance on the behavioral interview. Inter-rater
      reliability for assessing interview performance was quantified with an intraclass
      correlation coefficient (ICC1,1). Receiver operating characteristic (ROC) curves
      and associated validity indices were used to analyze variables that distinguished
      graduates who did and did not pass the NPTE on their first attempt (alpha =
      0.05). The ICC1,1 for assessing interview performance was 0.749. Performance on
      the verbal subscale of the GRE (ROC curve area = 0.734, p = 0.007) and behavioral
      interview (ROC curve area = 0.685, p = 0.034) were statistically significant
      predictors of NPTE performance. This study provides evidence supporting the
      contributions of the behavioral interview and verbal subscale of the GRE to
      predict NPTE performance and assist admissions decisions.

PMID- 18630786
TI  - A cross-disciplinary Statewide healthcare workforce analysis.
AB  - A statewide study was conducted to examine the healthcare workforce from the
      perspectives of the individual healthcare worker and employer as a basis for
      evidence-based workforce planning. The workforce minimum data set recommended by
      Colleagues in Caring was used to analyze job satisfaction, intention to leave
      current position, intention to leave profession, and reasons for such intentions
      in members of four professions (medical laboratorians, respiratory therapists,
      radiographers, and registered nurses) in a rural state. Statewide hospital
      vacancy and turnover rates for these disciplines also were analyzed. The study
      found that an aging workforce exists across these four healthcare disciplines.
      Despite relatively high satisfaction with their positions, a substantial
      proportion of this sample--over 20% for each profession--reported being "somewhat
      likely" or "very likely" to leave their position in the next 12 months. Top
      reasons for these intentions varied by profession and range from career mobility
      opportunities to job/organization dissatisfaction and stress. Nevertheless,
      vacancy and turnover rates in the hospital setting for all professions were
      comparatively modest. Implications for policy and research methods are detailed.

PMID- 18630787
TI  - Disability law and health care education.
AB  - Health care education programs, regardless of the discipline, will face similar
      challenges and issues related to students with disabilities. These are likely to
      include issues related to admission, retention, and academic adjustments,
      auxiliary aids, and services. A review of the literature reveals limited
      information beyond medical and nursing education programs, although students with
      disabilities are enrolled in education programs in other health care disciplines.
      Recent research indicates that students with disabilities are enrolling in health
      care education programs with increasing frequency. Educators and administrators
      will benefit from a better understanding of disability law and how it impacts
      education programs. Further, this knowledge should allow health care educators to
      be more proactive in regard to students with disabilities and to maintain a
      greater degree of autonomy over their respective programs. This report reviews
      pertinent legislation and case law as it applies to students with disabilities in
      health care education.

PMID- 18630788
TI  - Direct-to-consumer advertising: its effects on stakeholders.
AB  - The escalating growth in the development of pharmaceutical drugs has caused the
      pharmaceutical industry to market drugs directly to consumers. Direct-to-consumer
      (DTC) advertising has increased immensely in the past 15 years and continues to
      grow each year. The advantages of DTC advertising include an increase in consumer
      knowledge, patient autonomy, and possibly providing physicians and pharmacists
      with up-to-date information about the recent trends in the marketplace. However,
      there is also an equally notable list of disadvantages, which include concerns
      about the quality of information provided, loss in physician productivity due to
      time spent convincing patients that what they want is not in their best interest,
      and increases in the reimbursement expenditure of the insurers. Because of these
      conflicting outcomes, the issue of DTC advertising has become controversial. This
      report offers an overview of DTC advertising and focuses on its effects on
      physicians, pharmacists, consumers, insurers, the government, and pharmaceutical
      manufacturers.

PMID- 18630789
TI  - Developing an honor statement for university students in graduate professional
      programs.
AB  - Student and faculty in our graduate professional programs in physical and
      occupational therapy recently acted on their concerns regarding an upsurge in
      behaviors that were contrary to those associated with academic integrity (e.g.,
      cheating, plagiarism, etc.). To address this issue, student leaders and faculty
      members met to consider ideas on how to reverse this negative trend, which
      ultimately led to the development of an honor statement for the department and
      establishment of a process for addressing issues related to academic integrity.
      We used a Delphi method to guide the process of collecting and distilling
      information, which involved a series of meetings, online surveys, and electronic
      voting. This article describes the process of formulating and refining that honor
      statement.

PMID- 18630790
TI  - Global warming, climate change, air pollution and allergic asthma.

PMID- 18630791
TI  - Manifestations of pulmonary tuberculosis in the elderly: a prospective
      observational study from north India.
AB  - BACKGROUND: There is scarcity of published literature on manifestations of
      pulmonary tuberculosis (PTB) among elderly patients in India. The aim of the
      present study was to compare the clinical, radiological and laboratory
      manifestations of PTB among young and elderly patients. METHODS: This prospective
      study involved 100 human immunodeficiency virus (HIV) negative patients with PTB.
      The demographic, clinical, radiological and laboratory manifestations were
      compared between young (n=50; under 60 years of age) and elderly (n=50; aged 60
      years and above) with PTB. RESULTS: Elderly patients, in comparison to younger
      patients, tended to be heavier smokers and had more co-morbidities (40% vs 8%; p
      < 0.05). They presented more frequently with constitutional symptoms (except
      fever) and less frequently with respiratory symptoms. The mean duration of
      symptoms and rate of sputum smear-positivity for acid-fast bacilli was similar in
      both groups. Both the groups were similar with respect to physical examination
      and chest radiograph findings. Median values of erythrocyte sedimentation rate
      and total leukocyte count were significantly higher and lower respectively in the
      elderly patients. CONCLUSIONS: The presentation of PTB in elderly patients
      differs from that of younger patients by the predominance of constitutional
      rather than respiratory symptoms. A high index of suspicion is required to make a
      timely diagnosis of tuberculosis in the elderly.

PMID- 18630792
TI  - Trends in bacterial pathogens of lower respiratory tract infections.
AB  - OBJECTIVES: This study was conducted to determine the bacterial aetiology of
      lower respiratory tract infections in this environment as well as update the
      clinicians in the various antimicrobial alternatives available in the treatment.
      METHODS: Between September 2002 and February 2005, 157 bacterial pathogens from
      556 patients with lower respiratory tract infections were isolated from sputum
      specimens, and subjected to susceptibility testing, using standard bacteriologic
      techniques. RESULTS: Out of the 556 cases, only 150 (27%) had an established
      bacterial aetiology. One pathogen was demonstrated in 143 (95.3%) patients and
      seven (4.7%) had mixed infections. The most prevalent single pathogen was
      Klebsiella pneumoniae (38%) while the most prevalent bacterial combination was
      Klebsiella and Pseudomonas species (2%). Isolates of Klebsiella pneumoniae were
      susceptible to ciprofloxacin, gentamicin and ceftriaxone. CONCLUSIONS:
      Bacteriological diagnosis and antibiotic resistance surveillance are
      indispensable in the effective management of lower respiratory tract infections.

PMID- 18630793
TI  - Transbronchial needle aspiration in the diagnosis and staging of lung cancer.
AB  - OBJECTIVES: This study was aimed to determine effects of transbronchial needle
      aspiration (TBNA) in diagnosis and staging of lung cancer. METHODS: Records of 55
      patients who underwent TBNA in our Chest Department from February 2002 to
      December 2004 were reviewed retrospectively. RESULTS: Out of 55 patients who had
      undergone TBNA, 30 were diagnosed to have lung cancer after complete work up.
      Transbronchial needle aspiration was positive for malignant cells in 12 out of 20
      lung cancer patients with mediastinal lymphadenopathy on computed tomographic
      scan (CT scan) of the thorax. Mediastinoscopy was positive for malignancy in
      three cases and the remaining five had bulky lymph node enlargement which was
      considered malignant, given the histologic diagnosis established by other
      methods. Transbronchial needle aspiration was also positive for two other
      patients who had lymph nodes less than 1 cm size. The sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy of TBNA in the
      diagnosis of lung cancer patients were 58%, 100%, 100%, 37% and 66%,
      respectively. CONCLUSIONS: The study demonstrates that TBNA is an efficient
      procedure in the diagnosis and staging of lung cancer. The diagnostic yield is
      increased when there is lymph node enlargement on CT scan of the thorax and
      reduces the need for mediastinoscopy.

PMID- 18630794
TI  - Intrapleural fibrinolytic therapy in complicated parapneumonic effusion and
      empyema: present status.
AB  - Pneumonia remains one of the commonest community- and hospital-acquired infection
      despite the advent of potent antimicrobial agents. A significant number of
      patients with pneumonia develop parapneumonic effusions. The parapneumonic
      effusion may be "simple" consisting of free-flowing, clear exudative fluid which
      almost resolves completely with antibiotics alone. In case of delayed or
      inappropriate treatment, some of these simple effusions progress to complicated
      parapneumonic effusions and empyema. The management of these types of effusions
      with intercostal tube drainage and antibiotics fails most of the time due to the
      presence of thick viscous fluid and multiple pleural space loculations. The
      various therapeutic options available at this stage include intrapleural
      instillation of fibrinolytic agents, breaking down of loculations or
      decortication either by video-assisted thoracosopic surgery (VATS) or thoracotomy
      and open drainage procedures. Video-assisted thoracic surgery is a better option
      but it is neither easily available nor affordable by majority of patients in
      developing countries, like India. Intrapleural instillation of fibrinolytic
      agents has been found to be a useful adjunctive therapy in various small
      uncontrolled and randomised trials. After a recent and first large multicentre
      trial which showed that this therapy does not have any significant effect in
      reducing mortality and need for surgery in patients with pleural infection, the
      role of intrapleural fibrinolytics has become more controversial. In view of
      this, there is a need to re-define its role especially in the developing
      countries.

PMID- 18630795
TI  - Hydatid disease of the lung mimicking a pericardial cyst.
AB  - We report a young girl who presented to us with chest discomfort and had a
      paracardiac mass on chest radiograph. Computerised tomographic (CT) scan of the
      thorax was suggestive of pericardial cyst. Hydatid serology was negative. The
      cyst was excised.

PMID- 18630796
TI  - Massive haemothorax: a presentation of pulmonary arteriovenous malformation.
AB  - Arteriovenous malformations of the lung are relatively uncommon lesions with
      varied clinical presentation. Nearly half of these are associated with Osler
      Rendu-Weber disease. Magnetic resonance angiography is an accurate and non
      invasive diagnostic modality. We report a case of a 56-year-old male who had
      massive haemothorax due to rupture of a pulmonary arteriovenous malformation
      arising from the right interlobar artery.

PMID- 18630797
TI  - Idiopathic pulmonary haemosiderosis: complete remission with steroids.
AB  - A 13-year-old boy was diagnosed as a case of idiopathic pulmonary haemosiderosis
      on the basis of clinical presentation, radiological assessment and open lung
      biopsy. The patient had a complete clinical and radiological remissions with oral
      corticosteroids.

PMID- 18630798
TI  - Trauma: an unusual aetiology of pulmonary pseudocyst.
AB  - Traumatic pulmonary pseudocyst due to blunt chest trauma is rare. It is a
      clinical entity that manifests itself with minor clinical and major radiological
      signs. We report a case of a 16-year-old girl, who during an attack by a violent
      cow sustained a chest impact that resulted in a traumatic pulmonary pseudocyst,
      confirmed with a computed tomographic (CT) scan of the chest. The patient
      recovered with conservative management.

PMID- 18630799
TI  - Wegener's granulomatosis mimicking paraneoplastic syndrome.
AB  - Wegener's granulomatosis is a distinct clinico-pathological entity characterised
      by a triad of upper and lower respiratory disease and renal involvement, although
      atypical presentations can be seen. These patients characteristically have small
      vessel vasculitis and or granulomatous vasculitis and are usually anti
      neutrophilic cytoplasmic antibody (ANCA) positive. We present a case of Wegener's
      granulomatosis that clinically mimicked a lung neoplasm with a paraneoplastic
      syndrome. Biopsy and histopathological evaluation of a readily accessible
      subcutaneous nodule showed small vessel vasculitis. Correlation with clinical
      data and ANCA positivity led to a definite diagnosis.

PMID- 18630800
TI  - Effect of NO-synthase and arginase inhibition in airway hyperreactivity.
AB  - BACKGROUND: The decreased L-arginine bioavailability, the basic substrate for
      nitric oxide synthesis, can be one of the factors contributing to the airways
      hyperreactivity. OBJECTIVES: We investigated the effect of various inhibitors of
      the enzyme activities utilizing L-arginine in a guinea pig model of experimental
      ovalbumin-induced airway hyperreactivity. METHODS: We used the in vivo pre
      treatment with non-specific inhibitor of NO synthase No-nitro-L-arginine
      metylester (L-NAME) and relatively specific inhibitor of inducible NO synthase-
      aminoguanidine. Inhibitors were administered in one-shot (on the 14th day, 30
      minutes before the inhalation of ovalbumin) or in a long-time regime (during the
      whole period of sensibilization by ovalbumin--14 days). We administered the
      inhibitor of arginase Nomega-hydroxy-L-arginine (NOHA) to the tracheal and lung
      tissue smooth muscle strips from sensibilized animals. RESULTS: We observed an
      increase in the tracheal smooth muscle response to histamine in animals that
      received an inhalation dose of L-NAME (40 mg/kg b.w.) or aminoguanidine (50 mg/kg
      b.w.) 30 minutes before the inhalation of ovalbumin but did not evoke any
      significant difference in the reactivity of lung tissue smooth muscle. Tracheal
      smooth muscle responded with enhanced contraction amplitude to histamine after
      chronic pre-treatment with L-NAME or aminoguanidine. The inhibition of arginase
      with NOHA in vitro decreased the tracheal and lung tissue smooth muscle
      reactivity to histamine. CONCLUSION: The results suggest that NO-synthase
      isoforms as well as arginase are involved in the production of NO and in the
      control of bronchomotoric tonus (Fig. 4, Tab. 2, Ref. 31). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 18630801
TI  - Neuroendoscopy.
AB  - The discovery of optic bulb paved the way for the development of safe endoscopic
      systems not only with diagnostic ability, but also suitable for treatment. At the
      beginning of the 20th century, the first attempts to use an endoscope in the
      treatment of hydrocephalus have been made with encouraging results. Although the
      invention of an implantable shunt system slowed down the development of
      neuroendoscopy, the progress in fiberoptics and image processing has established
      the potential for the neuroendoscopy boom. Together with microneurosurgery,
      neuroendoscopy has established the concept of minimally invasive neurosurgery
      (Fig. 4, Ref. 16). Full Text (Free, PDF) www.bmj.sk.

PMID- 18630802
TI  - Shock--manifestation of pulmonary atresia with aorto-pulmonary collaterals and
      single ventricle physiology in a 2-day neonate.
AB  - BACKGROUND: The combination of pulmonary valve atresia and ventricular septal
      defect accounts for about 2% of cases of congenital heart disease. Most of the
      cases have intracardiac anatomy of Tetralogy Fallot and present with cyanosis in
      neonatal age. OBJECTIVES: To report a case of a newborn with rare combination of
      pulmonary atresia, ventricular septal defect and single ventricle physiology
      presenting with shock very early following birth. METHODS AND RESULTS: We
      describe a newborn infant who developed shock with severe metabolic acidosis and
      respiratory distress several hours following birth. Cardiac ultrasound showed
      pulmonary atresia and ventricular septal defect with single ventricle physiology.
      Cardiac cathetrisation revealed major aorto-pulmonary collaterals with an
      excessive pulmonary blood flow. Resuscitative measures resulted in hemodynamic
      stability. However, due to unfavorable prognosis, a decision not to undertake
      surgical palliation was made. Withdrawal of intensive care led to rapid demise of
      the patient. CONCLUSIONS: We report a case of a newborn with pulmonary atresia,
      ventricular septal defect and single ventricle physiology in whom an excessive
      flow through major aorto-pulmonary collaterals led to shock and death very early
      following birth (Fig. 1, Ref. 5). Full Text (Free, PDF) www.bmj.sk.

PMID- 18630803
TI  - Severe acute otitis media in children.
AB  - Acute otitis media (AOM) is one of the most common infections in children.
      Recently it was noticed that there is a marked increase in relapse of severe
      acute otitis media in children. There is also an increase in number of
      hospitalized children due to severe AOM, with etiological agent resistant to
      antibiotics. There is a rise of infections, caused by highly resistant
      Streptococcus pneumoniae, too. Authors retrospectively reviewed children
      hospitalized at the Children's ENT Department in Children's University Hospital
      in Bratislava, from January 2005 to December 2006, due to severe acute otitis
      media. They mainly focused on etiological agent, antibiotics resistance as well
      as alternatives of treatment and prevention of severe AOM. During 2 years, there
      were 76 children aged from 4 months to 14 years hospitalized with severe AOM. The
      most frequent etiological agent was Streptococcus pneumoniae in 37 cases; this
      was almost in 70% of cases resistant to routine antibiotics. In 7 cases there was
      mastoiditis, and mastoidectomy or antrotomy had to be done in 6 cases. To
      establish a diagnosis and start appropriate treatment it is necessary to identify
      etiological agent and its sensitivity. An increasing bacterial resistance is
      forcing us to prescribe antibiotics rationally. When severe AOM occurs,
      tympanotomy and insertion of ventilation tubes, exceptionally mastoidectomy, is
      often required (Fig. 13, Tab. 3, Ref. 18). Full Text (Free, PDF) www.bmj.sk.

PMID- 18630804
TI  - Perforation of gallbladder.
AB  - OBJECTIVE: Gallbladder perforation is a rare but life threatening complication of
      acute cholecystitis. Aim of this study is to present our clinical experience with
      gallbladder perforation. MATERIAL AND METHODS: Thirty-seven of retrospectively
      reviewed 1042 acute cholecystitis patients were found to have gallbladder (GB)
      perforation. Perforations due to trauma, iatrogenic causes, and gallbladder
      carcinoma were excluded. RESULTS: Abdominal ultrasound (US) showed gall stones in
      all of the patients with type-I and type-II gallbladder perforations (GBP),
      extensive intraperitoneal free fluid in 9 patients with type-I GBP, and a small
      amount of pericholecystic free fluid in 7 patients with type-II GBP. Abdominal US
      did not show GB wall defect in any of the patients, but showed intraperitoneal
      free gall stone in one type-I and one type-II GBP patients. CT revealed GB wall
      thickening in all of the patients, gall stones in 7 patients, extensive
      intraperitoneal free fluid in 7 patients, a small amount of pericholecystic free
      fluid in 8 patients, and GB perforation sites in 4 patients. Abdominal CT and US
      detected subhepatic abscesses in 3 patients. CONCLUSION: Early diagnosis of
      gallbladder perforation and immediate surgical intervention are of crucial
      importance. Unfortunately, the limited success of US and CT for detecting the GBP
      let us advocate early and urgent surgery (Tab. 3, Ref. 13). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 18630805
TI  - Outcomes after surgical repair of sinus venosus atrial septal defect in children.
AB  - OBJECTIVES: Review of outcomes for children undergoing surgical repair of sinus
      venosus atrial septal defect (SVASD) and proposal of optimal treatment strategy.
      BACKGROUND: Unlike secundum-type atrial septal defect (ASD II), surgical
      correction of SVASD is more challenging and carries higher risk of postoperative
      complications. Several surgical techniques have been proposed to avoid them;
      however, the data on long-term follow-up are limited. METHODS: Between 1992-2005,
      85 patients underwent surgery for SVASD at our institution. 78 and 7 operations
      were performed through full and partial sternotomy, respectively. The mean age
      was 7.7 years (2 months -19 years). All patients with SVASD and no partial
      anomalous pulmonary venous drainage (PAPVD) or PAPVD in right atrium (n = 24)
      underwent the single-patch repair. Among patients with SVASD and PAPVD in SVC, 22
      and 39 patients underwent intracaval baffle and Warden procedure, respectively.
      Clinical, electrocardiographic and echocardiographic follow-ups were available
      for all patients. RESULTS: There were no deaths, reoperations, residual atrial
      septal defects and pulmonary vein stenosis. Two patients had SVC stenosis.
      Permanent arrhythmias were noted in 24 patients (28.2%). The rate of new
      arrhythmias in the intracaval baffle and Warden subgroup was 54.6% vs 23.1% (p =
      0.01). Moreover, two and one patient from the intracaval baffle subgroup receive
      antiarrhythmics and had a pacemaker implanted, respectively. CONCLUSION: Surgical
      treatment of SVASD is associated with excellent results and minimal morbidity.
      The Warden procedure is preferred in patients with SVASD and PAPVD in SVC because
      of lower incidence of postoperative arrhythmias (Tab. 1, Fig. 4, Ref. 23). Full
      Text (Free, PDF) www.bmj.sk.

PMID- 18630806
TI  - The first experience with the high-resolution multi-slice CT-angiography in
      pediatric cardiology in Slovakia.
AB  - OBJECTIVES: The high-resolution multi-slice computed tomography angiography (HRMS
      CTA) is a new imaging method characterized by a precise isotropic imaging of any
      cardiovascular system structure. The purpose of this study was to review the
      first experience with the high-resolution multi-slice HRMS-CTA in pediatric
      patients with congenital heart defects as well as with acquired cardiac diseases
      in the Slovak Republic. METHODS: We retrospectively reviewed benefits of HRMS-CTA
      and its influence on the subsequent choice of the most appropriate management in
      20 patients with pulmonary atresia with ventricular septal defect and multiple
      aortopulmonary collaterals (PA, VSD, MAPCAs) and in 15 patients with different
      diagnoses with expected benefit from HRMS-CTA in terms of an exact delineation of
      extra-cardiac vascular structures. RESULTS: The delineation of the examined extra
      cardiac structures was very detailed and clear in all 35 patients. All findings
      definitely contributed to the choice of the most appropriate management not only
      in PA, VSD, MAPCAs patients (20), but also in 15 patients with different
      diagnoses. CONCLUSIONS: HRMS-CTA is a new complementary imaging method with the
      potential to replace invasive catheterization procedures in large number of
      patients who need extra-cardiac vascular structure imaging (Fig. 1, Ref. 18).
      Full Text (Free, PDF) www.bmj.sk.

PMID- 18630807
TI  - Adult obesity at the beginning of the 21st century: epidemiology, pathophysiology
      and health risk.
AB  - Obesity is defined as increased body weight caused by excessive accumulation of
      fat. Due to a very long period of undernutrition in human history, the
      contemporary human body regulation mechanisms seem to be biased in favor of
      preserving fat rather to eliminate it. At the highest risk are populations that
      suddenly gained wealth. The shift from undernutrition to overnutrition has
      occurred in a very short time, in many population groups in less than in one
      generation. The increase of obesity prevalence observed in the 20th century
      continues until present and it appears this trend will further continue in almost
      all countries in the world. Contemporary prevalence of adult obesity is very high
      in USA (33% in both gender), in oil-rich Arabian countries (30% in males, 40 % in
      females) and in European Union (up to 25% in both gender). The aim of
      contemporary research is to understand the molecular and neural systems which the
      body uses to regulate its storage of energy in the form of fat and how these
      systems can become unbalanced, leading to obesity. In spite of discovery of new
      hormones (e.g. leptin produced in adipose tissue) and of new mechanisms, the
      prevention and treatment of obesity remains an open problem. Obesity is
      associated with an increased risk of numerous comorbidities such as type 2
      diabetes, metabolic syndrome, hypertension, cardiovascular diseases and
      osteoarthritis. In USA the impact of obesity on mortality may have decreased over
      time, perhaps because of improvements in public health and medical care. New data
      from USA and China suggest the lowest all-cause mortality in persons with a body
      mass index, BMI between 23.0 and 27.0 (Fig. 6, Tab. 1, Ref. 29). Full Text (Free,
      PDF) www.bmj.sk.

PMID- 18630808
TI  - Determination of the centre of gravity in the methodology of kinesiotherapy for
      osteoporotic patients.
AB  - The article brings a biomechanical analysis of the determination of the position
      of gravity centre of trainee in plane, both graphically and by calculation. The
      importance of determining the position of the gravity centre in different
      postures of a trainee should not be underestimated, as it belongs to the basic
      principles in the development of methodology of kinesitherapy for both healthy
      and ill people. An erudite methodology of kinesitherapy for osteoporotic patients
      can be developed only on the basis of biomechanical analysis of each exercise
      element, i.e., it is necessary to have the knowledge of the position of gravity
      centre, support area and the distance of the gravity centre projection from the
      stability limit, magnitude of the stability angle, and regularity of mechanical
      stress acting upon weakened osteoporotic vertebrae. A correctly chosen
      methodology of kinesitherapy for osteoporotic patients prevents the development
      of vertebral microfractures, prevents the patient from falling during the
      exercise, and stimulates the bone neoformation with increasing the bone mineral
      density and periosteal apposition of bone, followed by the enlargement of the
      bone cross sectional area as well as that of the cross sectional moment of
      inertia. The resulting effect is an improvement in bone quality and its
      mechanical resistance (Tab. 2, Fig. 7, Ref. 11). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 18630809
TI  - The globalization of cross-cultural medical education and patient-centered care.

PMID- 18630810
TI  - Response to cross-cultural medical education and training: thoughts from the UK.

PMID- 18630811
TI  - The compelling need for cross-cultural medical education.

PMID- 18630812
TI  - Synonymy of negative prefixes concerns also medical English.
AB  - Human interest in negation dates back to thousands of years ago and concerns not
      only Linguistics, Logic, Psychology, and Mathematics. A lot of everyday words
      have negative meaning expressed by means of negative prefixes. Such type of
      negation is called word, or affixal negation. Affixal negation is a process of
      word-formation, by which a new word is built from a word stem, usually through
      the addition of an affix, either at the beginning (prefix) or end of the stem
      (suffix). Sometimes the same word can be negated by means of more than just one
      negative prefix. Such pairs of words become synonymous (Ref. 12). Full Text
      (Free, PDF) www.bmj.sk.

PMID- 18630813
TI  - Glucose transporter type 1 (GLUT-1) deficiency.

PMID- 18630814
TI  - CMV infection and CMV disease in kidney transplant recipients--our experiences.

PMID- 18630815
TI  - [Adjuvant therapies: the example of breast cancer].
AB  - Adjuvant chemotherapy, initiated following surgery, aims at controlling
      "microscopic" metastatic disease before its progression to a "clinical"
      recurrence. Its efficiency in localized breast cancer was officially demonstrated
      in 1992 in the Early Breast Cancer Trialists' Collaborative Group meta-analysis.
      This analysis helped clarify the benefits of therapeutic interventions according
      to progression stage, age and tumour biological features, especially in the
      presence of hormone receptors. Later on, new trials further defined the benefits
      of modern therapies, and especially trastuzumab in patients overexpressing HER2.
      The assessment of the theoretical benefits of adjuvant therapies takes into
      account the risk of individual recurrence and the potential decrease of the
      latter following a given therapeutic intervention--this decrease depending on
      tumor biological features. Deciding whether an adjuvant therapy should be
      initiated is difficult since benefits (observed in the long term) are often
      moderate while toxicities (immediately observed) are significant. The development
      of national and regional therapeutic guidelines markedly diminished the arbitrary
      aspect of the decision. Developing tools which could help implying the patient in
      this therapeutic decision is a priority.

PMID- 18630817
TI  - [Poisonings. Opportunities for improved medical management].

PMID- 18630816
TI  - [Obstructive colloid cyst of the third ventricle].

PMID- 18630818
TI  - [Poison episodes reported to French poison control centers in 2006].
AB  - This article presents an overview of the human exposures reported to the ten
      French poison control centres in 2006 for the toxicological response to
      emergencies. The figures are extracted from the national database of poisonings
      and from the activity reports. In 2006,197 042 cases of human exposure have been
      completed and 130463 analyzed. The vast majority (82.5%) of poison exposures are
      unintentional. Thus, children from 1 to 4 years old are the most concerned
      (46.3%); pharmaceuticals (28%), followed by the household products (19.2%) are
      mostly involved. The intentional intoxications (14.1%) are mainly suicides
      (92.6%) and women are more concerned (62.4%). Pharmaceuticals (65.8%), especially
      paracetamol (9.8%), are most often involved. Fatal poisonings (138) are mostly
      intentional (65.4%) and are observed among people from 30 to 59 years old
      (53.8%). Ethanol (15.2%), carbon monoxide (14.5%) and fires smoke (5.8%) are the
      agents most frequently involved in fatal poisonings.

PMID- 18630819
TI  - [Decisions to make when dealing with a medication overdose].
AB  - The management of a poisoned patient in the emergency department implies that the
      attending physician takes several decisions. Among them is the immediate
      disposition of the patient, that is where he is going to be observed, and
      ultimately when can he be discharged from the hospital. This article presents
      some key elements to take into consideration when taking those decisions. By
      example, these decisions are taken after a risk analysis. However, this is not
      without pitfalls such as with medications that can kill when a toddler ingested
      them in one unit or with medications with delayed toxic manifestations.
      Furthermore, during the patient observation or just before discharge, a social
      evaluation will need to be done. Moreover, if the ingestion is voluntary, a
      psychiatric evaluation will also need to be done.

PMID- 18630820
TI  - [Interest of toxicological analysis for poisonings].
AB  - The clinical approach of the poisoned patients is mainly based on the analysis of
      the circumstances of intoxication and the search for toxidromes. Toxicological
      analysis aims to detect the toxicants or measure their concentrations, in order
      to confirm the hypothesis of poisoning, to evaluate its severity and to help the
      follow-up regarding the treatment efficiency. Emergent toxicological analysis
      appears only useful if the method is specific and the results rapidly obtained.
      Therefore, systematic screening using immunochesmistry-based tests is not
      recommended in the situation of emergency. Measurement of blood concentrations of
      the toxicants is only indicated if it may influence the patient management.
      However, in the perspective of research, the study of toxicokinetic/toxicodynamic
      relationships, i.e. the relationships between the toxicant effects and its blood
      concentrations, may be helpful to understand the inter-individual variability of
      the response to a toxicant.

PMID- 18630821
TI  - [New antidotes in toxicology].
AB  - New antidotes appeared in the French pharmacopoeia (fomepizole, Viperfav), and
      old drugs, usually unused in toxicology, saw their indications enlarged in an
      antidotic activity (glucose and insulin, L-carnitine, octreotide). Fomepizole is
      an antidote for toxic alcohol and glycol intoxications, which is much easier to
      handle than ethylic alcohol and as efficient as the classical antidote of this
      kind of intoxication. Octreotide improves the result of hypertonic glucose
      infusion in sulfonylurea derivatives intoxications, by blocking insulin release.
      The glucose-insulin association allows the myocardium to use the main energy
      substrate necessary for its action in the setting of beta-blocking and calcium
      channel blocking agents intoxications when they are associated to a cardiogenic
      shock. Viperfav is a polyvalent antivenom used in European adders envenomations,
      which showed its effectiveness and safety. Levocarnitine allows to correct the
      wrong metabolic pathway induced by a deficit in carnitine in valproic acid
      intoxications.

PMID- 18630822
TI  - [Acute carbon monoxide poisoning].
AB  - Carbon monoxide (CO) poisoning is still complicated by a high mortality and
      morbidity rate. Diagnosis can be obvious but is most of time difficult and
      sometimes remained unknown. It is usually based on clinical signs and must be
      confirmed by assessment of CO level in room air or in patient's expired breathing
      or blood and detection of a source. Mild neurological sequelae are very common.
      Normobaric oxygen is the first line treatment. Comatose and pregnant patients
      must undergo hyperbaric oxygen. All CO poisoning has to be declared to sanitary
      authority, which will in turn conduct a technical inspection to remove the
      source. The patient must be informed that he is at risk of new poisoning and of
      neurological complications. Progress in prevention and research in therapeutics
      are needed in order to reduce CO related morbidity.

PMID- 18630823
TI  - [Extracorporeal life support for poisonings with cardiotoxicants].
AB  - Acute poisonings with cardiotoxicants are responsible of significant morbidity
      and incompressible mortality, mainly among youths. Their incidence is increasing.
      Death mainly results from cardiac failure refractory to pharmacological
      treatments as well as sudden cardiac arrest refractory to cardiopulmonary
      resuscitation. Determination of the exact mechanism of shock is essential to
      guide adequate treatments. Treatment is supportive including high-dosage
      catecholamines and may require antidotes. Administration of other inotropic
      agents (including glucagon, phosphodiesterase inhibitors, calcium salts, and
      euglycemic insulin) may be discussed, although their efficacy is still not
      clearly established. Extracorporeal life support allows organ perfusion until
      reversal of cardiac dysfunction and elimination of the toxicant. Several cases of
      survival using this exceptional technique were reported in the literature. Thus,
      based on these reports, extracorporeal life support has gained a recognized place
      in the therapeutic arsenal of acute poisonings.

PMID- 18630824
TI  - [Acute acetaminophen overdose].
AB  - Acute ingestion of acetaminophen can induce a dose-dependent hepatotoxicity and
      lead to death. The management of acute acetaminophen poisoning at the early stage
      is well codified. A reported amount of ingestion > 200 mg/kg in a child, > 150
      mg/kg in an adult (125 mg/kg if risk factors are present) require
      hospitalisation. Activated charcoal is administered within 1-2 hours of
      ingestion. AST/ALT levels are measured on admission, 12 hours after, and
      according to outcome every 12-24 h. N-acetylcysteine (NAC) administration within
      8-10 hours protects against acetaminophen-induced hepatotoxicity. The two
      protocols of NAC administration, intravenous and oral, have a comparable
      effectiveness. NAC is indicated if the serum acetaminophen level drawn 4 hours
      after ingestion and plotted on the nomograme falls above the "200 mg/L-4 hours"
      line. Nomograme is not usable with repeated acute ingestion or repeated
      supratherapeutic doses; presence of risk factors (enzymatic induction,
      malnutrition, chronic alcoholism) must be taken into account ("100 mg/L - 4
      hours" line). Outcome is favorable with respect to these conditions.

PMID- 18630825
TI  - [Paraquat poisoning].

PMID- 18630826
TI  - [Progress in the treatment of organophosphorus poisoning].

PMID- 18630827
TI  - [The role of chelating agents in childhood lead poisoning].

PMID- 18630829
TI  - [Caution: Javel water!].

PMID- 18630830
TI  - [Residents, work hours and patient safety].

PMID- 18630828
TI  - [Treatment of acute poisoning by illicit drugs. Recommendations of the French
      Language Resuscitation Society (SRLF)].

PMID- 18630831
TI  - [Aortic valve insufficiency].

PMID- 18630832
TI  - [Addiction and addictive behavior. Part I - Smoking].

PMID- 18630833
TI  - [Diagnosis of cancer. Signs, staging and prognosis].

PMID- 18630834
TI  - [Autoimmune diseases: epidemiology, diagnosis and treatment].

PMID- 18630835
TI  - [Geriatric hospital care. Geriatrics during the 19th and 20th centuries].

PMID- 18630836
TI  - Sclerosing angiomatoid nodular transformation of the spleen.
AB  - OBJECTIVE: To study clinical and pathologic features of sclerosing angiomatoid
      nodular transformation (SANT) and differential diagnosis, we reviewed splenectomy
      specimens from the Department of Pathology, First Affiliated Hospital, School of
      Medicine, Zhejiang University (January 1990 to December 2006) and another case
      from consultation at Second Jiaxing Municipal Hospital, Zhejiang Province,
      finding 7 cases of this lesion. STUDY DESIGN: Clinicopathologic characteristics
      and immunophenotype of 7 cases of SANT were studied. RESULTS: Five cases were
      incidentally found during routine examination. One had concurrent hepatic
      angioma. Microscopically, all cases were characterized by multiple angiomatoid
      nodules of various sizes embedded in fibrosclerotic stroma. Each nodule was
      composed of slit-like, round or irregularly shaped vascular spaces lined by plump
      endothelial cells and interspersed by a population of spindle or ovoid cells. In
      one case, an angiomatoid nodular lesion and a hamartoma-like lesion appeared
      together. Heterogeneous immunohistochemical features of the lining cells were
      revealed. CD34 was expressed in the narrow, well-formed capillaries and CD8 in
      some sinusoid-like structures, but without CD34 expression. CD31 staining
      highlighted numerous lining cells and interspersed cells. Some lining cells were
      focally CD68 positive. CONCLUSION: SANT is a rare lesion. Based on morphologic
      and immunohistochemical features, it may be a variant of splenic hamartoma.

PMID- 18630837
TI  - Correlation of modified Gleason grading of prostate carcinoma with age, serum
      prostate specific antigen and tumor extent in needle biopsy specimens.
AB  - OBJECTIVE: To investigate the correlation of biopsy grade with age, serum
      prostate specific antigen (PSA) and biopsy tumor extent using the conventional
      and modified Gleason grading systems. STUDY DESIGN: A total of 828 consecutive
      needle biopsy specimens of prostate carcinoma were collected from the years 1995
      and 2000 (graded with conventional Gleason grading) and 2006 and 2007 (graded
      with modified Gleason grading). RESULTS: Both conventional and modified Gleason
      grading correlated with age, serum PSA, percent positive biopsies and percent
      cancer length. In 2006-2007, the patients were on average younger and more biopsy
      cores were taken per patient. Serum PSA and percent positive cores were lower
      than in the 1995 and 2000 group, indicating a stage shift downward, but the
      Gleason scores were nevertheless higher. CONCLUSION: Conventional and modified
      Gleason grading both correlated with age, serum PSA and cancer involvement in
      needle biopsies. With modified Gleason grading there is a grade shift upward
      despite the downstaging that has been observed in recent years.

PMID- 18630838
TI  - Automated cerebrospinal fluid cytology.
AB  - OBJECTIVE: To evaluate the Abbott CELL-DYN Sapphire cytometer for cerebrospinal
      fluid (CSF) cell count and differentiation. METHODS: One hundred three analyses
      of CSF cells by the CELL-DYN Sapphire were compared with routine cell count and
      microscopic differentiation and correlation coefficients calculated. RESULTS: The
      total cell count of both methods correlated well. The detection of erythrocytes
      was good (0.898), and a higher content of erythrocytes >100/microL had little
      effect on total leukocyte count. The correlation between both methods was best
      with higher leukocyte counts >25/microL (r=0.987), whereas at cell counts
      <25/microL, the correlation was considerably less precise (r=0.613). For the
      differentiation of cells, lymphocytes and neutrophils showed moderate
      correlation. The results for monocytes and eosinophils did not correlate.
      CONCLUSION: The results for the total cell count in this study are comparable
      with those achieved with the Bayer Advia 120. While the Abbott CELL-DYN Sapphire
      yielded slightly better results for erythrocytes and total cell count with a
      higher erythrocyte content, the Advia 120 achieved slightly better results of
      lymphocyte and neutrophil count in a previous study.

PMID- 18630839
TI  - A study of the reproducibility of a fluorescence in situ hybridization bladder
      cancer detection assay.
AB  - OBJECTIVE: To assess the reproducibility of the UroVysion fluorescence in situ
      hybridization (FISH) bladder cancer detection assay. STUDY DESIGN: Thirteen
      specimens (2 negative, 3 low-level positive [1-10% abnormal cells], 5 mid-level
      positive [11-75%], and 3 high-level positive [>75%]) were analyzed by 7
      cytotechnologists. Each cytotechnologist rendered an overall diagnosis of
      positive or negative and determined the percentage of abnormal urothelial cells
      for all positive specimens. RESULTS: The interobserver reproducibility of the
      assay was 100% for mid-level and high-level positive specimens, 93% for negative
      specimens, and 78% for low-level positive specimens. The range of percent
      abnormal determinations was highest for mid-level positive specimens, with mean
      SDs of 1.8%, 16.4% and 10.1% for the low-, mid-, and high-level positives,
      respectively. CONCLUSION: There was a high level of reproducibility among the mid
      and high-level positive specimens. The reproducibility for low-level positive
      specimens was lowest, suggesting that such specimens should be reviewed by a
      second technologist to ensure an accurate diagnosis. The findings of this study
      are important for further elucidating the clinical value of quantitative FISH
      analysis in the management of patients undergoing FISH testing for bladder
      cancer.

PMID- 18630840
TI  - Changes in prostate cancer at radical prostatectomy during the prostate specific
      antigen era: an Italian experience.
AB  - OBJECTIVE: To assess changes in prostate cancer clinical and pathologic features
      by review of 15 years' experience with radical prostatectomy. STUDY DESIGN: A
      total of 596 consecutive patients who underwent open or laparoscopic radical
      prostatectomy (RP) between 1991 and 2006 were included. All had clinically
      localized prostate cancer. Surgical specimens were analyzed or blindly reviewed
      by a uropathologist, and whole-mount sections were prepared. Statistical analysis
      evaluated whether significant changes in clinical and pathologic variables
      occurred over time. RESULTS: Median prostate specific antigen (PSA) values at
      diagnosis significantly decreased over time. Definite stage migration was
      observed, with significant increase of organ-confined tumors. Incidence of
      seminal vesicle and lymph node involvement declined steadily. Median tumor volume
      decreased significantly over time (p<0.001). Incidence of nonsignificant cancers
      at RP increased significantly, reaching 25.6% in 2006. PSA value has
      progressively lost correlation with prostate cancer volume and today correlates
      only with prostate gland volume. CONCLUSION: Prostate cancer stage and volume at
      diagnosis have steadily decreased in the last 15 years, likely reflecting
      increasing use of PSA testing. In early prostate cancer, PSA level no longer
      correlates with tumor volume.

PMID- 18630841
TI  - Nuclear morphometry and AgNOR quantification: computerized image analysis on
      ovarian mucinous tumor imprints.
AB  - OBJECTIVE: To determine the morphometric characteristics of nuclei and silver
      stained nucleolar organizer regions (AgNORs) on cytologic imprints and their
      value in differential cytodiagnosis of benign, atypical proliferative
      (borderline) and malignant ovarian mucinous tumors. STUDY DESIGN: Forty-six
      mucinous ovarian tumor imprints (16 benign, 15 borderline, 15 malignant), were
      analyzed. Nuclear area, outline, "shape factor" and "form factor" were measured
      on Papanicolaou-stained smears. AgNOR quantification included 7 variables related
      to the number and area of single, cluster, total and relative AgNOR content per
      nucleus and the size distribution of AgNORs. RESULTS: Nuclear area and shape
      factor allowed distinguishing borderline and malignant tumors. The nuclear area
      in benign tumors was larger than that in borderline tumors; malignant tumors had
      the highest values. Single and cluster AgNORs were statistically significantly
      different in borderline tumors compared with malignant tumors, except for the
      cluster AgNOR area. The total AgNOR area, number and relative area increased from
      benign through malignant tumors, with statistically significant differences among
      all groups. By AgNOR size distribution, small AgNORs discriminate malignant from
      borderline and benign tumors. CONCLUSION: Combining nuclear morphometry and AgNOR
      analysis on cytologic imprints could be a diagnostically useful method in the
      assessment of mucinous ovarian tumors.

PMID- 18630842
TI  - Image analysis of DNA content and nuclear morphometry for predicting
      radiosensitivity of nasopharyngeal carcinoma.
AB  - OBJECTIVE: To investigate the relationship among nuclear DNA content, nuclear
      morphology, clinical response, and radiosensitivity in nasopharyngeal carcinoma
      (NPC) and the suitability of image cytometric analysis of DNA content and nuclear
      morphology for predicting radiosensitivity of NPC prior to radiotherapy. STUDY
      DESIGN: Nuclear DNA content and morphology features were detected by image
      cytometric analysis in 51 biopsy specimens of NPC prior to radiotherapy. The
      radiotherapeutic effect experienced by the NPC patients was classified as CR
      (complete response [i.e., complete tumor disappearance]) and PR (partial response
      [i.e., residual tumor]) according to pathologic analysis of tumor specimens after
      completion of the scheduled treatment. RESULTS: The mean DNA index; the
      percentage of cells with the DNA pattern of 2C, 5C, aneuploidy respectively; the
      mean nuclear area; the mean nuclear perimeter and the mean nuclear diameter in
      the CR group were significantly higher than they were in the PR group.
      CONCLUSION: DNA content and nuclear morphometry by image cytometric analysis were
      significantly correlated with patient outcome and radiosensitivity of NPC. Other
      measurements of more biomarkers for predicting the radiosensitivity of NPC await
      further study.

PMID- 18630843
TI  - Image preprocessing improves Fourier-based texture analysis of nuclear chromatin.
AB  - OBJECTIVE: To investigate whether preprocessing of digitized images can improve
      the image analysis of chromatin of cytologic preparations using Fast Fourier
      Transformation (FFT). STUDY DESIGN: In a preprocessing step the nuclear borders
      of the segmented nuclei were smoothed, thus avoiding the Airy ring artifact. We
      tested this method, comparing the inertia values of digitalized cardiomyocyte
      nuclei of rats of different ages. Furthermore, we created in silicio nuclear
      images with chromatin alterations at or nearby the nuclear edge in order to
      investigate the robustness of our method. RESULTS: After preprocessing, the FFT
      derived variable inertia discriminated significantly better the chromatin
      structure of the nuclei at different ages in every frequency range. The
      investigation on simulated nuclei revealed that within the frequency ranges from
      1.8 microm to 0.72 microm smoothing of the borders does not interfere with the
      detection of chromatin changes at the nuclear border. CONCLUSION: Smoothing of
      borders in segmented images can improve the analysis of Fourier-derived variables
      of the chromatin texture.

PMID- 18630844
TI  - Angiogenesis and molecular markers as specific therapeutic targets in renal cell
      carcinomas.

PMID- 18630846
TI  - Communicating treatment possibilities at the chair.

PMID- 18630845
TI  - Maintaining proper dental records.
AB  - Patients today are better educated and more assertive than ever before, and
      dentists must be equipped to protect themselves against malpractice claims.
      Handle every record as if it could be summoned to a courtroom and scrutinized by
      an attorney, judge, or jury. Complete, accurate, objective, and honest patient
      records are the only way to defend against any clinical and/or legal problems
      that might arise. By implementing the suggestions mentioned in this course,
      dental team members can minimize the legal risks associated with the delivery of
      dental care and hopefully promote greater patient understanding of their rights
      and privileges to their record.

PMID- 18630847
TI  - Successful associateships don't just happen.

PMID- 18630848
TI  - Air Force dental service maximizes technology throughout clinics.

PMID- 18630849
TI  - Educating patients: staff response to patient misunderstanding.
AB  - Members of a dentist's staff may be the best allies in promptly identifying
      patient misunderstandings related to their dental care. The doctor and his team
      should discuss the various ways in which patients may indicate misunderstandings
      about the dental practice's clinical or business policies. A staff member's
      prompt and thoughtful response can go a long way toward preventing patients'
      suspicion, non-compliance, and dissatisfaction.

PMID- 18630850
TI  - Medical emergency in your office one year later: you've been served! What do you
      do now?

PMID- 18630851
TI  - Average electron tunneling route of the electron transfer in protein media.
AB  - We present a new theoretical method to determine and visualize the average
      tunneling route of the electron transfer (ET) in protein media. In this, we
      properly took into account the fluctuation of the tunneling currents and the
      quantum-interference effect. The route was correlated with the electronic factor
      <TDA(2)> in the case of ET by the elastic tunneling mechanism. We expanded
      <TDA(2)> by the interatomic tunneling currents <Jab(2)>'s. Incorporating the
      quantum-interference effect into the mean-square interatomic tunneling currents,
      denoted as <Jab(2)>, we could express <TDA(2)> as a sum of variant Planck's over
      2pi(2)<Jab(2)>. Drawing the distribution of <Jab(2)> on the protein structure, we
      obtain the <Jab(2)> map which visually represents which parts of bonds and spaces
      most significantly contribute to <TDA(2)>. We applied this method to the ET from
      the bacteriopheophytin anion to the primary quinone in the bacterial
      photosynthetic reaction center of Rhodobacter sphaeroides. We obtained <Jab(2)>'s
      by a combined method of molecular dynamics simulations and quantum chemical
      calculations. In calculating <Jab(2)>, we found that much destructive
      interference works among the interatomic tunneling currents even after taking the
      average. We drew the <Jab(2)> map by a pipe model where atoms a and b are
      connected by a pipe with width proportional to the magnitude of <Jab(2)>. We
      found that two groups of <Jab(2)>'s, which are mutually coupled with high
      correlation in each group, have broad pipes and form the average tunneling
      routes, called Trp route and Met route. Each of the two average tunneling routes
      is composed of a few major pathways in the Pathways model which are fused at
      considerable part to each other. We also analyzed the average tunneling route for
      the ET by the inelastic tunneling mechanism.

PMID- 18630852
TI  - Optimization of interactions between a cationic conjugated polymer and
      chromophore-labeled DNA for optical amplification of fluorescent sensors.
AB  - Cationic conjugated polymers (CCPs) have been widely utilized as signal
      amplifiers in biosensors to improve the detection sensitivity through
      fluorescence resonance energy transfer (FRET) from CCPs to dye-labeled probes or
      targets. This paper investigates the effect of sodium dodecyl sulfate (SDS) on
      energy transfer between a cationic polyfluoreneethynylene copolymer (P1) and
      Texas Red labeled single-stranded DNA (ssDNA-TR). The presence of SDS in solution
      affects both the optical properties of P1 and TR emission within P1/ssDNA-TR
      complexes, which provides basic information on the role of SDS in FRET between P1
      and ssDNA-TR. Although the quantum yield of P1 decreases in the presence of low
      concentrations of SDS, the presence of SDS reduces TR fluorescence quenching
      within P1/ssDNA-TR complexes and increases the number of optically active polymer
      repeat units within the proximity of TR, which are beneficial to P1-sensitized TR
      emission. In the absence of SDS, FRET from P1 to ssDNA-TR provides a 2.6-fold
      enhancement in TR emission intensity as compared to that upon direct excitation
      of TR at 595 nm. At the optimum SDS concentration (5 microM), P1-sensitized TR
      signal output increases to 11.3-fold relative to direct excitation of TR. This
      study highlights the importance of modulation of the CCP/ssDNA-dye interaction in
      improving the signal output of dye-labeled DNA by CCP through FRET.

PMID- 18630853
TI  - Aggregation-enhanced emissions of intramolecular excimers in disubstituted
      polyacetylenes.
AB  - Whereas chain aggregation commonly quenches light emission of conjugated
      polymers, we here report a phenomenon of aggregation-induced emission enhancement
      (AIEE): luminescence of polyacetylenes is dramatically boosted by aggregate
      formation. Upon photoexcitation, poly(1-phenyl-1-alkyne)s and
      poly(diphenylacetylene)s emit blue and green lights, respectively, in dilute THF
      solutions. The polymers become more emissive when their chains are induced to
      aggregate by adding water into their THF solutions. The polymer emissions are
      also enhanced by increasing concentration and decreasing temperature. Lifetime
      measurements reveal that the excited species of the polymers become longer-lived
      in the aggregates. Conformational simulations suggest that the polymer chains
      contain n=3 repeat units that facilitate the formation of intramolecular
      excimers. The AIEE effects of the polymers are rationalized to be caused by the
      restrictions of their intramolecular rotations by the aggregate formation.

PMID- 18630854
TI  - Single ion diffusive transport within a Poly(styrene sulfonate) polymer brush
      matrix probed by fluorescence correlation spectroscopy.
AB  - Diffusive transport within complex environments is a critical piece of the
      chemistry occurring in such diverse membrane systems as proton exchange and
      bilayer lipid membranes. In the present study, fluorescence correlation
      spectroscopy was used to evaluate diffusive charge transport within a strong
      polyelectrolyte polymer brush. The fluorescent cation rhodamine-6G was used as a
      counterion probe molecule, and the strong polyelectrolyte poly(styrene sulfonate)
      was the polymer brush. Such strong polyelectrolyte brushes show promise for
      charge storage applications, and thus it is important to understand and tune
      their transport efficiencies. The polymer brush demonstrated preferential
      solvation of the probe counterion as compared to solvation by the aqueous solvent
      phase. Additionally, diffusion within the polymer brush was strongly inhibited,
      as evidenced by a decrease in diffusion constant of 4 orders of magnitude. It
      also proved possible to tune the transport characteristics by controlling the
      solvent pH, and thus the ionic strength of the solvent. The diffusion
      characteristics within the charged brush system depend on the brush density as
      well as the effective interaction potential between the probe ions and the brush.
      In response to changes in ionic strength of the solution, it was found that these
      two properties act in opposition to each other within this strong polyelectrolyte
      polymer brush environment. A stochastic random walk model was developed to
      simulate interaction of a diffusing charged particle with a periodic potential,
      to show the response of characteristic diffusion times to electrostatic field
      strengths. The combined results of the experiments and simulations demonstrate
      that responsive diffusion characteristics in this brush system are dominated by
      changes in Coulombic interactions rather than changes in brush density. More
      generally, these results support the use of FCS to evaluate local charge
      transport properties within polyelectrolyte brush systems, and demonstrate that
      the technique shows promise in the development of novel polyelectrolyte films for
      charge storage/transport materials.

PMID- 18630855
TI  - Formation of intramolecular poly(4-hydroxystyrene) dimer radical cation.
AB  - Poly(4-hydroxystyrene) (PHS) has been used in lithography as a backbone polymer
      and is also a promising material for extreme-ultraviolet or electron beam
      lithography. The dynamics of PHS radical cations generated upon exposure to
      electron beam were investigated. The transient absorption of PHS was observed in
      the near-infrared region in p-dioxane solutions by pulse radiolysis. Charge
      resonance (CR) bands that represent pi-pi interaction between the two
      chromophores of the intramolecular PHS dimer radical cation were observed,
      whereas p-cresol shows no distinct CR band. Although the radical cations of
      phenol derivatives are known to be easily deprotonated, it was found that the
      dimer radical cation formation leads to less deprotonation by its charge
      resonance stabilization.

PMID- 18630856
TI  - Mechanistic study on electrochemical deposition of conjugated polymers in
      centrifugal fields.
AB  - This work presents a detailed study of the mechanism for the electrochemical
      deposition of conjugated polymers on anodes in centrifugal fields. The rate of
      the electrochemical deposition of polyaniline was affected significantly by a
      centrifugal acceleration force of 315 g. However, no centrifugal effects were
      observed on the electrochemical deposition of poly(3,4-ethylenedioxythiophene).
      It was found that the degree of the centrifugal effect generated depended greatly
      on the size of the oligomer aggregates just before their deposition. To further
      confirm the influence of size on electrochemical systems under centrifugal
      fields, we also carried out an electrochemical redox reaction using various sizes
      of vinylferrocene-immobilized polystylene latex particles.

PMID- 18630857
TI  - Special pair dance and partner selection: elementary steps in proton transport in
      liquid water.
AB  - Conditional and time-dependent radial distribution functions reveal the details
      of the water structure surrounding the hydronium during the proton mobility
      process. Using this methodology for classical multistate empirical valence bond
      (MS-EVB) and ab initio molecular dynamics trajectories, as well as quantal MS-EVB
      trajectories, we supply statistical proof that proton hops in liquid water occur
      by a transition from the H3O+[3H2O] Eigen-complex, via the H5O2+ Zundel-complex,
      to a H3O+[3H2O] centered on a neighboring water molecule. In the "resting period"
      before a transition, there is a distorted hydronium with one of its water ligands
      at a shorter distance and another at a longer distance than average. The identity
      of this "special partner" interchanges rapidly within the three first-shell water
      ligands. This is coupled to cleavage of an acceptor-type hydrogen bond. Just
      before the transition, a partner is selected by an additional translation of the
      H3O+ moiety in its direction, possibly enabled by loosening of donor-type
      hydrogen bonds on the opposite side. We monitor the transition in real time,
      showing how the average structure is converted to a distorted H5O2+ cation
      constituting the transitional complex for proton hopping between water molecules.

PMID- 18630858
TI  - Hybrid materials from intermolecular associations between cationic lipid and
      polymers.
AB  - Intermolecular associations between a cationic lipid and two model polymers were
      evaluated from preparation and characterization of hybrid thin films cast on
      silicon wafers. The novel materials were prepared by spin-coating of a
      chloroformic solution of lipid and polymer on silicon wafer. Polymers tested for
      miscibility with the cationic lipid dioctadecyldimethylammonium bromide (DODAB)
      were polystyrene (PS) and poly(methyl methacrylate) (PMMA). The films thus
      obtained were characterized by ellipsometry, wettability, optical and atomic
      force microscopy, Fourier transform infrared spectroscopy (FTIR), differential
      scanning calorimetry (DSC), and activity against Escherichia coli. Whereas
      intermolecular ion-dipole interactions were available for the PMMA-DODAB
      interacting pair producing smooth PMMA-DODAB films, the absence of such
      interactions for PS-DODAB films caused lipid segregation, poor film stability
      (detachment from the silicon wafer) and large rugosity. In addition, the well
      established but still remarkable antimicrobial DODAB properties were transferred
      to the novel hybrid PMMA/DODAB coating, which is demonstrated to be highly
      effective against E. coli.

PMID- 18630859
TI  - Modeling the phase behavior of H2S+n-alkane binary mixtures using the SAFT-VR+D
      approach.
AB  - A statistical associating fluid theory for potential of variable range has been
      recently developed to model dipolar fluids (SAFT-VR+D) [Zhao and McCabe, J. Chem.
      Phys. 2006, 125, 104504]. The SAFT-VR+D equation explicitly accounts for dipolar
      interactions and their effect on the thermodynamics and structure of a fluid by
      using the generalized mean spherical approximation (GMSA) to describe a reference
      fluid of dipolar square-well segments. In this work, we apply the SAFT-VR+D
      approach to real mixtures of dipolar fluids. In particular, we examine the high
      pressure phase diagram of hydrogen sulfide+n-alkane binary mixtures. Hydrogen
      sulfide is modeled as an associating spherical molecule with four off-center
      sites to mimic hydrogen bonding and an embedded dipole moment (micro) to describe
      the polarity of H2S. The n-alkane molecules are modeled as spherical segments
      tangentially bonded together to form chains of length m, as in the original SAFT
      VR approach. By using simple Lorentz-Berthelot combining rules, the theoretical
      predictions from the SAFT-VR+D equation are found to be in excellent overall
      agreement with experimental data. In particular, the theory is able to accurately
      describe the different types of phase behavior observed for these mixtures as the
      molecular weight of the alkane is varied: type III phase behavior, according to
      the scheme of classification by Scott and Konynenburg, for the H2S+methane
      system, type IIA (with the presence of azeotropy) for the H2S+ethane and+propane
      mixtures; and type I phase behavior for mixtures of H2S and longer n-alkanes up
      to n-decane. The theory is also able to predict in a qualitative manner the
      solubility of hydrogen sulfide in heavy n-alkanes.

PMID- 18630860
TI  - Thermodynamic origin of hofmeister ion effects.
AB  - Quantitative interpretation and prediction of Hofmeister ion effects on protein
      processes, including folding and crystallization, have been elusive goals of a
      century of research. Here, a quantitative thermodynamic analysis, developed to
      treat noncoulombic interactions of solutes with biopolymer surface and recently
      extended to analyze the effects of Hofmeister salts on the surface tension of
      water, is applied to literature solubility data for small hydrocarbons and model
      peptides. This analysis allows us to obtain a minimum estimate of the hydration
      b1 (H2O A(-2)), of hydrocarbon surface and partition coefficients Kp,
      characterizing the distribution of salts and salt ions between this hydration
      water and bulk water. Assuming that Na+ and SO4(2-) ions of Na2SO4 (the salt
      giving the largest reduction in hydrocarbon solubility as well as the largest
      increase in surface tension) are fully excluded from the hydration water at
      hydrocarbon surface, we obtain the same b1 as for air-water surface
      (approximately 0.18 H2O A(-2)). Rank orders of cation and anion partition
      coefficients for nonpolar surface follow the Hofmeister series for protein
      processes, but are strongly offset for cations in the direction of exclusion
      (preferential hydration). By applying a coarse-grained decomposition of water
      accessible surface area (ASA) into nonpolar, polar amide, and other polar surface
      and the same hydration b1 to interpret peptide solubility increments, we
      determine salt partition coefficients for amide surface. These partition
      coefficients are separated into single-ion contributions based on the observation
      that both Cl- and Na+ (also K+) occupy neutral positions in the middle of the
      anion and cation Hofmeister series for protein folding. Independent of this
      assignment, we find that all cations investigated are strongly accumulated at
      amide surface while most anions are excluded. Cation and anion effects are
      independent and additive, allowing successful prediction of Hofmeister salt
      effects on micelle formation and other processes from structural information
      (ASA).

PMID- 18630861
TI  - Alkylammonium-based protic ionic liquids. Part I: Preparation and physicochemical
      characterization.
AB  - Novel alkylammonium-cation-based protic acid ionic liquids (PILs) were prepared
      through a simple and atom-economic neutralization reaction between an amine, such
      as diisopropylmethylamine, and diisopropylethylamine, and a Bronsted acid, HX,
      where X is HCOO-, CH 3COO-, or HF2-. The density, viscosity, acidic scale,
      electrochemical window, temperature dependency of ionic conductivity, and thermal
      properties of these PILs were measured and investigated in detail. Results show
      that protonated alkylammonium such as N-ethyldiisopropyl formate and N
      methyldiisopropyl formate are liquid at room temperature and possess very low
      viscosities, that is, 18 and 24 cP, respectively, at 25 degrees C. An
      investigation of their thermal properties shows that they present a wide liquid
      range up to -100 degrees C and a heat thermal stability up to 350 degrees C.
      Alkylammonium-based PILs have a relatively low cost and low toxicity and show a
      high ionic conductivity (up a 8 mS cm(-1)) at room temperature. They have wide
      applicable perspectives for fuel cell devices, thermal transfer fluids, and acid
      catalyzed reaction media and catalysts as replacements of conventional inorganic
      acids.

PMID- 18630862
TI  - Comment on "re-examination of reversibility in reaction models for the
      spontaneous emergence of homochirality".

PMID- 18630864
TI  - Intramolecular charge transfer reaction, polarity, and dielectric relaxation in
      AOT/water/heptane reverse micelles: pool size dependence.
AB  - Intramolecular charge transfer (ICT) reaction in a newly synthesized molecule, of
      4-(1-morpholenyl) benzonitrile (M6C), in AOT/water/heptane reverse micelles at
      different pool sizes has been studied by using steady-state and time-resolved
      fluorescence emission spectroscopy. The pool size dependences of the reaction
      equilibrium constant and reaction rate have been explained in terms of the
      average polarity of the confined solvent pools estimated from the fluorescence
      emission Stokes shift of a nonreactive probe, coumarin 153, dissolved in these
      microemulsions. The complex permittivity measurements in the frequency range
      0.01<or=nu/GHz<or=2 for these microemulsions at different pool sizes
      (0<or=w0<or=40) and AOT concentrations (0.1<or=c/M<or=0.5) at 298.15 K have also
      been performed. At sufficient water content, a large dispersion with a relaxation
      time of approximately 600 ps has been observed at approximately 300 MHz and
      attributed to the average reorientation of water molecules residing in the close
      vicinity of the polar interface of the AOT headgroup and n-heptane. The
      reorientation of these interfacial water molecules is probably responsible for
      the nanosecond component observed in numerous polar solvation dynamics
      experiments in these reverse micelles. Subsequently, the estimated polarity and
      the measured reorientational time scale have been used to explain the dramatic
      slowing down of the ICT reaction rate and its dependence on pool size in these
      confined environments.

PMID- 18630865
TI  - Raman scattering properties of a protonic titanate HxTi2-x/4[symbol: see
      text]x/4O4.H2O ([symbol: see text], vacancy; x=0.7) with lepidocrocite-type
      layered structure.
AB  - Raman scattering spectroscopy is employed to characterize a layered titanate
      HxTi2-x/4[symbol: see text]x/4O4.H2O ([symbol: see text]: vacancy; x=0.7) with
      lepidocrocite (gamma-FeOOH)-type layered structure. Nine Raman lines
      corresponding to (3Ag+3B1g+3B3g) Raman-active modes expected from this
      orthorhombic structure (space group D2h25-Immm) are recorded at 183, 270, 387,
      449, 558, 658, 704, 803, and 908 cm(-1), which are assigned to Ti-O lattice
      vibrations within the two-dimensional (2D) lepidocrocite-type TiO6 octahedral
      host layers. These intrinsic Raman bands present a clear signature that can be
      used for probing the protonic titanate HxTi2-x/4[symbol: see text]x/4O4.H2O and
      the 2D titanate nanosheets, as well as their corresponding derivates.

PMID- 18630866
TI  - Transport properties of highly ordered heterogeneous ion-exchange membranes.
AB  - Model "ordered" heterogeneous ion exchange membranes are made with ion exchange
      particles heaving ion exchange capacity in the range 3 to 2.5 meq/gr (dry basis)
      and diameters ranging from 37 to 7 microm and 2 component room-temperature
      vulcanizing silicon rubber as a polymeric matrix, by applying an electric field
      normal to the membrane surface during preparation. These membranes were shown to
      have an improved ionic conductivity compared with "nonordered" membranes based on
      the same ion exchange content (for instance, at 10% resin content "nonordered"
      membranes show <10(-5) mS/cm while "ordered" membranes have conductivity of 1
      mS/cm). The transport properties of ordered membranes were compared with those of
      nonordered membranes, through the current-voltage characteristics. Limiting
      currents measured for the ordered membranes were significantly higher than those
      of the nonordered membranes with the same resin concentration. In addition,
      higher limiting currents were observed in ordered membranes as the resin
      particles became smaller. Energy dispersion spectrometry analyses revealed that
      the concentration of cation exchange groups on the membrane surface was higher
      for ordered membrane as compared to that of nonordered membranes. This implies
      that the local current density for the conducting domains at the surface of the
      nonordered membranes is higher, leading to higher concentration polarization and,
      eventually, to lower average limiting current densities. The effect of ordering
      the particles on the membrane conductivity and transport properties was studied,
      and the advantages of the ordered membranes are discussed.

PMID- 18630868
TI  - On the nature of the intermediates and the role of chloride ions in Pd-catalyzed
      allylic alkylations: added insight from density functional theory.
AB  - The reactivity of intermediates in palladium-catalyzed allylic alkylation was
      investigated using DFT (B3LYP) calculations including a PB-SCRF solvation model.
      In the presence of both phosphine and chloride ligands, the allyl intermediate is
      in equilibrium between a cationic eta(3)-allylPd complex with two phosphine
      ligands, the corresponding neutral complex with one phosphine and one chloride
      ligand, and a neutral eta(1)-allylPd complex with one chloride and two phosphine
      ligands. The eta(1)-complex is unreactive toward nucleophiles. The cationic
      eta(3)-complex is the intermediate most frequently invoked in the title reaction,
      but in the presence of halides, the neutral, unsymmetrically substituted eta(3)
      complex will be formed rapidly from anionic Pd(0) complexes in solution. Since
      the latter will prefer both leaving group ionization and reaction with
      nucleophiles in the position trans to phosphorus, it can rationalize the observed
      "memory effect" (a regioretention) in the title reaction, even in the absence of
      chiral ligands.

PMID- 18630867
TI  - Resonance Raman characterization of the peroxo and hydroperoxo intermediates in
      cytochrome P450.
AB  - Resonance Raman (RR) studies of intermediates generated by cryoreduction of the
      oxyferrous complex of the D251N mutant of cytochrome P450(cam) (CYP101) are
      reported. Owing to the fact that proton delivery to the active site is hindered
      in this mutant, the unprotonated peroxo-ferric intermediate is observed as the
      primary species after radiolytic reduction of the oxy-complex in frozen solutions
      at 77 K. In as much as previous EPR and ENDOR studies have shown that annealing
      of this species to approximately 180 K results in protonation of the distal
      oxygen atom to form the hydroperoxo intermediate, this system has been exploited
      to permit direct RR interrogation of the changes in the Fe-O and O-O bonds caused
      by the reduction and subsequent protonation. Our results show that the nu(O-O)
      mode decreases from a superoxo-like frequency near approximately 1130 cm(-1) to
      792 cm(-1) upon reduction. The latter frequency, as well as its lack of
      sensitivity to H/D exchange, is consistent with heme-bound peroxide formulation.
      This species also exhibits a nu(Fe-O) mode, the 553 cm(-1) frequency of which is
      higher than that observed for the nonreduced oxy P450 precursor (537 cm(-1)),
      implying a strengthened Fe-O linkage upon reduction. Upon subsequent protonation,
      the resulting Fe-O-OH fragment exhibits a lowered nu(O-O) mode at 774 cm(-1),
      whereas the nu(Fe-O) increases to 564 cm(-1). Both modes exhibit a downshift upon
      H/D exchange, as expected for a hydroperoxo-ferric formulation. These
      experimental RR data are compared with those previously acquired for the wild
      type protein, and the shifts observed upon reduction and subsequent protonation
      are discussed with reference to theoretical predictions.

PMID- 18630869
TI  - Identification and characterization of novel immunogenic proteins of
      Streptococcus suis serotype 2.
AB  - Streptococcus suis, a zoonotic pathogen, caused serious outbreaks in humans with
      high mortality rates in the past decade. To develop safer and more effective
      vaccines, particularly for human protection, cell wall and extracellular proteins
      of S. suis serotype 2 were analyzed by an immunoproteomic approach in this study.
      Thirty-two proteins with high immunogenicity were identified and 22 of them were
      newly identified. Further analyses of 9 selected proteins revealed that (1) these
      9 proteins were expressed in all tested virulent S. suis serotype 2 isolates, (2)
      antisera against 6 of the selected proteins efficiently killed the bacteria by
      opsonized phagocytosis in human blood, and (3) significantly higher levels of
      serum antibodies against 3 proteins were detected in both patients and infected
      swines. Therefore, our results suggest the 3 proteins (SSU98_0197, SSU98_1094 and
      SSU1664) have strong potential to be vaccine candidates.

PMID- 18630871
TI  - Pd(I) phosphine carbonyl and hydride complexes implicated in the palladium
      catalyzed oxo process.
AB  - Reduction of compound "Pd(bcope)(OTf)2" [bcope = (c-C8H14-1,5)PCH2CH2P(c-C8H14
      1,5); OTf = O3SCF3] with H2/CO yields a mixture of Pd(I) compounds
      [Pd2(bcope)2(CO)2](OTf)2 (1) and [Pd2(bcope)2(mu-CO)(mu-H)](OTf) (2), whereas
      reduction with H2 or Ph3SiH in the absence of CO leads to [Pd3(bcope)3(mu3
      H)2](OTf)2 (3). Exposure of 3 to CO leads to 1 and 2. The structures of 1 and 3
      have been determined by X-ray diffraction. Complex [Pd2(bcope)2(CO)2](2+)
      displays a metal-metal bonded structure with a square planar environment for the
      Pd atoms and terminally bonded CO ligands and is fluxional in solution. DFT
      calculations aid the interpretation of this fluxional behavior as resulting from
      an intramolecular exchange of the two inequivalent P atom positions via a
      symmetric bis-CO-bridged intermediate. A cyclic voltammetric investigation
      reveals a very complex redox behavior for the "Pd(bcope)(OTf)2"/CO system and
      suggests possible pathways leading to the formation of the various observed
      products, as well as their relationship with the active species of the
      PdL2(2+)/CO/H2-catalyzed oxo processes (L2 = diphosphine ligands).

PMID- 18630872
TI  - Methyl proton contacts obtained using heteronuclear through-bond transfers in
      solid-state NMR spectroscopy.
AB  - A two-dimensional proton-mediated carbon-carbon correlation experiment that
      relies on through-bond heteronuclear magnetization transfers is demonstrated in
      the context of solid-state NMR of proteins. This new experiment, dubbed J-CHHC by
      analogy to the previously developed dipolar CHHC techniques, is shown to provide
      selective and sensitive correlations in the methyl region of 2D spectra of
      crystalline organic compounds. The method is then demonstrated on a
      microcrystalline sample of the dimeric protein Crh (2 x 10.4 kDa). A total of 34
      new proton-proton contacts involving side-chain methyl groups were observed in
      the J-CHHC spectrum, which had not been observed with the conventional
      experiment. The contacts were then used as additional distance restraints for the
      3D structure determination of this microcrystalline protein. Upon addition of
      these new distance restraints, which are in large part located in the hydrophobic
      core of the protein, the root-mean-square deviation with respect to the X-ray
      structure of the backbone atom coordinates of the 10 best conformers of the new
      ensemble of structures is reduced from 1.8 to 1.1 A.

PMID- 18630873
TI  - Selective metal deposition on photoswitchable molecular surfaces.
AB  - We report here a novel phenomenon: selective metal deposition on photoswitchable
      diarylethene (DAE) surfaces. Magnesium vapor was deposited by vacuum evaporation
      on the colored DAE but not on the uncolored surface. The selective deposition
      originates in the change of the glass transition temperature of the amorphous DAE
      film resulting from photoisomerization and therefore from changes of surface
      molecular motion. We clarified that Mg atoms on the uncolored surface actively
      migrated on the surface and were desorbed from the surface. The possibility of
      depositing other metals is also discussed. Light-controllable metal-integrated
      deposition was demonstrated as a new function of the photoswitchable molecular
      surfaces. This study reveals new features of the photoswitchable molecular
      surfaces, and their potential suggests bright prospects for future applications
      in organic electronics.

PMID- 18630870
TI  - Optimization of the central heterocycle of alpha-ketoheterocycle inhibitors of
      fatty acid amide hydrolase.
AB  - The synthesis and evaluation of a refined series of alpha-ketoheterocycles based
      on the oxazole 2 (OL-135) incorporating systematic changes in the central
      heterocycle bearing a key set of added substituents are described. The nature of
      the central heterocycle, even within the systematic and minor perturbations
      explored herein, significantly influenced the inhibitor activity: 1,3,4
      oxadiazoles and 1,2,4-oxadiazoles 9 > tetrazoles, the isomeric 1,2,4-oxadiazoles
      10, 1,3,4-thiadiazoles > oxazoles including 2 > 1,2-diazines > thiazoles > 1,3,4
      triazoles. Most evident in these trends is the observation that introduction of
      an additional heteroatom at position 4 (oxazole numbering, N > O > CH)
      substantially increases activity that may be attributed to a reduced
      destabilizing steric interaction at the FAAH active site. Added heterocycle
      substituents displaying well-defined trends may be utilized to enhance the
      inhibitor potency and, more significantly, to enhance the inhibitor selectivity.
      These trends, exemplified herein, emerge from both enhancements in the FAAH
      activity and simultaneous disruption of binding affinity for competitive off
      target enzymes.

PMID- 18630874
TI  - Organocatalytic mannich-type reactions of trifluoroethyl thioesters.
AB  - Direct organocatalytic Mannich-type reactions of thioesters provide for the
      expedient and diastereoselective synthesis of protected beta-amino acids. A
      variety of thioesters were found to be reactive with different imines under mild
      conditions to provide beta-amino acids in good yields. This chemistry was
      extended to a diastereo- and enantioselective variant.

PMID- 18630875
TI  - Characterization of the in situ structural and interfacial properties of the
      cationic hydrophobic heteropolypeptide, KL4, in lung surfactant bilayer and
      monolayer models at the air-water interface: implications for pulmonary
      surfactant delivery.
AB  - This study examines the various equilibrium in situ secondary structures of the
      pharmaceutical heteropolypeptide, KL 4, in the solid state, in solution, and in
      the monolayer state alone and mixed with dipalmitoylphosphatidylcholine (DPPC)
      and palmitoyloleoylphosphatidylglycerol (POPG). In situ surface circular
      dichroism spectroscopy, using a method first reported by Damodaran (Damodaran, S.
      Anal. Bioanal. Chem. 2003, 376, 182-188), of equilibrated KL 4, DPPC/KL 4,
      POPG/KL 4, and DPPC/POPG/KL 4 monolayers at the air-water interface was used to
      examine the in situ two-dimensional conformation of KL 4. Gravimetric vapor
      sorption by solid KL 4 was used to analyze the effects of water molecules on the
      conformation of KL 4 when confined as a monolayer at the surface of water. Solid
      state KL 4 conformation was determined by X-ray powder diffraction (XRPD). The
      equilibrium interfacial and spreading properties were measured at 25 degrees C,
      37 degrees C, and 45 degrees C using the Wilhelmy plate method and Langmuir film
      balance. Equilibrium phase transition temperatures were measured using
      differential scanning calorimetry (DSC). It was found that solid-state KL 4,
      which takes up very little water, exhibits beta-sheet and alpha-helix secondary
      structures, whereas KL 4 in solution appears to exist only as an alpha-helix. KL
      4 forms a stable, insoluble monolayer, exhibiting beta-sheet and aperiodic
      structures. These structures provide KL 4, when confined in two-dimensions, the
      structural flexibility to maximize favorable cationic lysine-water interactions
      and favorable leucine-leucine hydrophobic and van der Waals interactions; while
      effectively "shielding" the leucine residues away from water. In DPPC/KL 4
      monolayers, KL 4 retains its native beta-sheet and aperiodic structures,
      consistent with phase separation of DPPC and KL 4 in bilayers and monolayers. In
      POPG/KL 4 monolayers, KL 4 exhibits an increase in aperiodic secondary structures
      (loss of beta-sheet) to maximize favorable electrostatic interactions, consistent
      with the observed negative deviations from ideal monolayer mixing.

PMID- 18630876
TI  - Diversity-oriented synthesis of a drug-like system displaying the distinctive N-
      >C=O interaction.
AB  - This study describes the syntheses and characterization of two hydrazino ureas.
      These fold into a six-membered ring by virtue of the infrequently observed
      (delta+)N-->C=O (delta-) interaction when solvated by polar protic media. The
      highly polar functional group resulting from this interaction is hypothesized to
      especially reproduce electronic but also steric features of the transition states
      of peptide hydrolysis. The urea moiety constitutes an additional key element of
      modern HIV-1 protease (HIV PR) inhibitors and is meant to interact with the
      enzyme flaps. We have developed an efficient, convergent synthetic route to
      enantiopure compounds that uses CDI to couple two independent building blocks,
      one derived from amino acids and the other one from easily accessible hydrazines.
      It is thus amenable to rapid generation of diversity in order to screen for novel
      HIV PR inhibitors. A complete study using one- and two-dimensional NMR as well as
      UV spectroscopy confirmed the sole existence of the cyclic constitution of target
      compounds 7 and 8 in methanol. Total reversal to the linear aldehydic form is
      observed upon passage to apolar media.

PMID- 18630877
TI  - Formal total synthesis of (+/-)-estrone and zirconocene-promoted cyclization of 2
      fluoro-1,7-octadienes and ru-catalyzed ring closing metathesis.
AB  - A new and diastereoselective method for the synthesis of the estrone skeleton
      from a substituted styrene based on sequential 3-fold use of Cp 2ZrBu 2
      (oxidative addition-alkylation and two cyclization-alkylation sequences) and a
      ruthenium complex catalyzed RC-metathesis of a sterically hindered diene was
      developed. The prepared estratetraene was obtained in 7 steps from a commercially
      available starting material and thus the overall synthesis of estrone could be
      accomplished in 9 steps. Moreover, we have also found that the course of the
      reaction of substrates bearing the 2-halo-1,7-diene moiety with Cp 2ZrBu 2, i.e.,
      cyclization or oxidative addition to the C-X bond, could be controlled by the
      nature of the halogen leaving group.

PMID- 18630878
TI  - Effect of beta-alkylthioethyl substitution in 1,3-dithianes: quasianchimeric
      assistance in photoinduced electron transfer?
AB  - Nanosecond laser flash photolysis (LFP) experiments show that the rates of ET
      quenching of triplet benzophenone by 2-alkyldithianes significantly decrease with
      bulkier substitution. Introduction of sulfur at the beta-position of the flexible
      alkyl chain reverses this trend, whereas such substitution at the alpha-position
      has negligible effect. This is rationalized in terms of the three electron two
      center bonds, favorable due to the formation of five-membered cyclic radical
      cations in the case of beta-substitution, which is supported by DFT computations.

PMID- 18630879
TI  - Tandem Friedel-Crafts annulation to novel perylene analogues.
AB  - Novel dialkyloxy- and dihydroxyoctahydroperylenes are regioselectively available
      via a new tandem Friedel-Crafts alkylation of tetrahydronaphthalene precursors
      followed by oxidative aromatization. Heating of 5-alkyloxy-1-tetralol with p
      toluenesulfonic acid in sulfolane gave the corresponding octahydroperylenes in
      moderate yields. Studies with Lewis acids and tetralin-1,5-diol in acetonitrile
      at room temperature provided the 4,10-dihydroxy analogue cleanly, albeit in
      reduced yields. Examples of these new series of perylene analogues were partially
      oxidized to the corresponding contiguously aromatic, anthracene core products or
      fully aromatized to 3,9-dialkyloxyperylenes in good yields.

PMID- 18630880
TI  - Concise total synthesis of (+)-crocacin C.
AB  - The cytotoxic natural product (+)-crocacin C ( 1) has been synthesized in 10
      linear steps from commercially available Evans' chiral propionimide in 5% overall
      yield (8 steps from Evans' chiral dipropionate synthon). No protecting groups
      were utilized.

PMID- 18630881
TI  - Synthesis of optically pure 2-azido-1-arylethanols with isolated enzymes and
      conversion to triazole-containing beta-blocker analogues employing click
      chemistry.
AB  - Both antipodes of 2-azido-1-arylethanols were synthesized with excellent optical
      purity via enzymatic reduction of the corresponding alpha-azidoacetophenone
      derivatives catalyzed by a recombinant carbonyl reductase from Candida magnoliae
      ( CMCR) or an alcohol dehydrogenase from Saccharomyces cerevisiae ( Ymr226c).
      This provides an effective route to this class of important compounds in
      optically pure form. ( S)-2-Azido-1-( p-chlorophenyl)ethanols reacted with
      alkynes employing click chemistry to afford high yields of optically pure
      triazole-containing beta-adrenergic receptor blocker analogues with potential
      biological activity.

PMID- 18630882
TI  - Substituent effect on the efficiency of desulfurizative rearrangement of allylic
      disulfides.
AB  - Crich ligation is a new method for the functionalization of peptides and proteins
      under mild conditions. To more fully understand the mechanism of the ligation and
      to explore the effect of substitution on its efficiency, a systematic theoretical
      study is carried out for the first time. It is found that the MP2 method wrongly
      predicts the substituent effect whereas the ONIOM(CCSD(T):B3LYP) method
      overestimates the free energy barriers by ca. 4 kcal/mol. Only the
      ONIOM(G3B3:B3LYP) method is found to be reliable as well as feasible for studying
      the ligation. The rate-limiting step of the ligation is found to be the [2,3]
      sigmatropic rearrangement of the alkyl allyl disulfide, followed by an S N2
      phosphine-mediated desulfurization. The S-S bond is significantly polarized
      during the rearrangement and, therefore, the reaction proceeds more rapidly in
      polar solvents. R S and R 3 substitutions elevate the free energy barrier of the
      ligation, whereas the R 2 substitution does not exert a useful effect. Only the
      substitution at R 1 can effectively reduce the free energy barrier of the
      reaction to less than 20 kcal/mol (a value required to allow the reaction to
      complete in minutes at 25 degrees C). Therefore, secondary and tertiary allyl
      alkyl disulfides can undergo the ligation at the room temperature. Marcus theory
      analysis indicates that the major factor for the retardation of the reaction by
      substituents at R S and R 3 and for the acceleration by substituents at R 1 is
      the thermodynamic equilibrium between the disulfide and thiosulfoxide. To shift
      the equilibrium to favor the ligation, placement of substituents at R 1 is
      obligatory for alkyl allyl disulfides. Nonetheless, alkyl buta-2,3-dienyl
      disulfides may also undergo the ligation at room temperature without the help of
      the R 1 substituent.

PMID- 18630883
TI  - Diastereoselective synthesis of useful building blocks by crotylation of beta
      branched alpha-methylaldehydes with potassium crotyltrifluoroborates.
AB  - The diastereoselective construction of stereotriads having consecutive methyl,
      hydroxy, and methyl substituents was realized by the substrate-controlled
      crotylation of beta-branched alpha-methylaldehydes with potassium
      crotyltrifluoroborates. Especially, crotylation of 2-(1,3-dithian-2-yl)propanal
      with potassium ( E)-crotyltrifluoroborate afforded, in good yield and with
      excellent diastereoselectivity, a useful building block that has different and
      potential functional groups on both ends.

PMID- 18630884
TI  - Enantiomerization of chiral uranyl-salophen complexes via unprecedented ligand
      hemilability: toward configurationally stable derivatives.
AB  - In the search for configurationally stable inherently chiral uranyl-salophen
      complexes, the newly synthesized compound 3 featuring a dodecamethylene chain was
      expected to be a promising candidate. Unexpectedly, dynamic HPLC on a
      enantioselective column showed that it still undergoes enantiomerization at high
      temperature. By comparison with the dynamic behavior of compounds 4 and 5, it was
      found that the enantiomerization rate is independent of the size of the ligand.
      This finding definitely rules out a jump rope-type mechanism for the
      enantiomerization process and points to reaction pathways involving preliminary
      rupture of one of the O...U coordinative bonds. This provides unprecedented
      evidence of the occurrence of ligand hemilability in metal-sal(oph)en complexes.
      Such findings inspired the synthesis of compound 6 endowed with a more rigid
      spacer, i.e., that derived from 4,4'-(1,4-phenylenediisopropylidene)bisphenol.
      DHPLC investigations showed that the new structural motif imparts a higher
      configurational stability, thus raising the half-life for the enantiomerization
      to more than 2 months at room temperature. This clearly establishes that this
      compound represents the first member of a new class of inherently chiral
      receptors, whose potential in chiral recognition and catalysis now can be
      feasibly explored.

PMID- 18630885
TI  - Total syntheses of (+/-)-crinine, (+/-)-crinamine, and (+/-)-6a-epi-crinamine via
      the regioselective synthesis and Diels-Alder reaction of 3-aryl-5-bromo-2-pyrone.
AB  - We have devised a new unified synthetic protocol to (+/-)-crinine, (+/-)
      crinamine, and (+/-)-6a- epi-crinamine from the Diels-Alder cycloadduct of 3-(3,4
      methylenedioxyphenyl)-5-bromo-2-pyrone with TBS vinyl ether. The requisite 3-(3,4
      methylenedioxyphenyl)-5-bromo-2-pyrone was prepared from the C3-selective Stille
      coupling reaction of 3,5-dibromo-2-pyrone. Also noted is that the vinyl bromide
      can be used as a handle for further derivatization.

PMID- 18630886
TI  - Cracks in magnetic nanocrystal films: do directional and isotropic crack patterns
      follow the same scaling law?
AB  - In this letter, we show that the use of nanocrystals enables new insights into
      the scaling law of crack patterns. Directional and isotropic crack patterns made
      of gamma-Fe2O3 nanocrystals follow the same scaling law, with the film height
      varying by 3 orders of magnitude. A simple two-dimensional computer model for
      elastic fracture also leads to the same scaling behavior for directional and
      isotropic cracks, in good agreement with the experiments.

PMID- 18630887
TI  - Programmable hierarchical three-component 2D assembly at a liquid-solid
      interface: recognition, selection, and transformation.
AB  - Recognition and selection are of fundamental importance for the hierarchical
      assembly of supramolecular systems. Coronene induces the formation of a hydrogen
      bonded isophthalic acid supramolecular macrocycle, and this well-defined
      heterocluster forces, in its turn, DBA1 to form a van der Waals stabilized
      honeycomb lattice, leading to a three-component 2D crystal containing nine
      molecules in the unit cell. The recognition and selection events enable efficient
      error correction and healing in redundant mixtures.

PMID- 18630888
TI  - Molecular anions.
AB  - The experimental and theoretical study of molecular anions has undergone
      explosive growth over the past 40 years. Advances in techniques used to generate
      anions in appreciable numbers as well as new ion-storage, ion-optics, and laser
      spectroscopic tools have been key on the experimental front. Theoretical
      developments on the electronic structure and molecular dynamics fronts now allow
      one to achieve higher accuracy and to study electronically metastable states,
      thus bringing theory in close collaboration with experiment in this field. In
      this article, many of the experimental and theoretical challenges specific to
      studying molecular anions are discussed. Results from many research groups on
      several classes of molecular anions are overviewed, and both literature citations
      and active (in online html and pdf versions) links to numerous contributing
      scientists' Web sites are provided. Specific focus is made on the following
      families of anions: dipole-bound, zwitterion-bound, double-Rydberg, multiply
      charged, metastable, cluster-based, and biological anions. In discussing each
      kind of anion, emphasis is placed on the structural, energetic, spectroscopic,
      and chemical-reactivity characteristics that make these anions novel,
      interesting, and important.

PMID- 18630890
TI  - A pentacyclic aurora kinase inhibitor (AKI-001) with high in vivo potency and
      oral bioavailability.
AB  - Aurora kinase inhibitors have attracted a great deal of interest as a new class
      of antimitotic agents. We report a novel class of Aurora inhibitors based on a
      pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from
      two early lead structures improves upon the best properties of each parent and
      compares favorably to a previously reported Aurora inhibitor, 39 (VX-680). The
      inhibitor exhibits low nanomolar potency against both Aurora A and Aurora B
      enzymes, excellent cellular potency (IC50 < 100 nM), and good oral
      bioavailability. Phenotypic cellular assays show that both Aurora A and Aurora B
      are inhibited at inhibitor concentrations sufficient to block proliferation.
      Importantly, the cellular activity translates to potent inhibition of tumor
      growth in vivo. An oral dose of 5 mg/kg QD is well tolerated and results in near
      stasis (92% TGI) in an HCT116 mouse xenograft model.

PMID- 18630891
TI  - Design, synthesis, and biological evaluation of 14-substituted aromathecins as
      topoisomerase I inhibitors.
AB  - The aromathecin or "rosettacin" class of topoisomerase I (top1) inhibitors is
      effectively a "composite" of the natural products camptothecin and luotonin A and
      the synthetic indenoisoquinolines. The aromathecins have aroused considerable
      interest following the isolation and total synthesis of 22-hydroxyacuminatine, a
      rare cytotoxic natural product containing the 12 H-5,11a-diazadibenzo[ b,
      h]fluoren-11-one system. We have developed two novel syntheses of this system and
      prepared a series of 14-substituted aromathecins as novel antiproliferative
      topoisomerase I poisons. These inhibitors are proposed to act via an
      intercalation and "poisoning" mechanism identical to camptothecin and the
      indenoisoquinolines. Many of these compounds possess greater antiproliferative
      activity and anti-top1 activity than the parent unsubstituted compound
      (rosettacin) and previously synthesized aromathecins, as well as greater top1
      inhibitory activity than 22-hydroxyacuminatine. In addition to potentially aiding
      solubility and localization to the DNA-enzyme complex, nitrogenous substituents
      located at the 14-position of the aromathecin system have been proposed to
      project into the major groove of the top1-DNA complex and hydrogen-bond to major
      groove amino acids, thereby stabilizing the ternary complex.

PMID- 18630892
TI  - Substituted 6-phenyl-2-naphthols. Potent and selective nonsteroidal inhibitors of
      17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1): design, synthesis,
      biological evaluation, and pharmacokinetics.
AB  - 17beta-Estradiol (E2) is implicated in the genesis and the development of
      estrogen-dependent diseases. Its concentration is mainly regulated by 17beta
      hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which catalyzes the reduction
      of the weak estrogen estrone (E1) to the highly potent E2. This enzyme is thus an
      important target for the treatment of hormone-dependent diseases. Thirty-seven
      novel substituted 6-phenyl-2-naphthols were synthesized and evaluated for 17beta
      HSD1 inhibition, selectivity toward 17beta-HSD2 and the estrogen receptors (ERs)
      alpha and beta, and pharmacokinetic properties. SAR studies revealed that the
      compounds most likely bind according to binding mode B to the active site, i.e.,
      the 6-phenyl moiety mimicking the steroidal A-ring. While substitution at the
      phenyl ring decreased activity, introduction of substituents at the naphthol
      moiety led to highly active compounds, especially in position 1. The 1-phenyl
      compound 32 showed a very high inhibitory activity for 17beta-HSD1 (IC50 = 20 nM)
      and good selectivity (17beta-HSD2 and ERs) and pharmacokinetic properties after
      peroral application.

PMID- 18630893
TI  - Identification and validation of human DNA ligase inhibitors using computer-aided
      drug design.
AB  - Linking together of DNA strands by DNA ligases is essential for DNA replication
      and repair. Since many therapies used to treat cancer act by causing DNA damage,
      there is growing interest in the development of DNA repair inhibitors.
      Accordingly, virtual database screening and experimental evaluation were applied
      to identify inhibitors of human DNA ligase I (hLigI). When a DNA binding site
      within the DNA binding domain (DBD) of hLigI was targeted, more than 1 million
      compounds were screened from which 192 were chosen for experimental evaluation.
      In DNA joining assays, 10 compounds specifically inhibited hLigI, 5 of which also
      inhibited the proliferation of cultured human cell lines. Analysis of the 10
      active compounds revealed the utility of including multiple protein conformations
      and chemical clustering in the virtual screening procedure. The identified ligase
      inhibitors are structurally diverse and have druglike physical and molecular
      characteristics making them ideal for further drug development studies.

PMID- 18630894
TI  - Slow self-activation enhances the potency of viridin prodrugs.
AB  - When the viridin wortmannin (Wm) is modified by reaction with certain
      nucleophiles at the C20 position, the compounds obtained exhibit an improved
      antiproliferative activity even though a covalent reaction between C20 and a
      lysine in the active site of PI3 kinase is essential to Wm's ability to inhibit
      this enzyme. Here we show that this improved potency results from an
      intramolecular attack by the C6 hydroxyl group that slowly converts these
      inactive prodrugs to the active species Wm over the 48 h duration of the
      antiproliferative assay. Our results provide a guide for selecting Wm-like
      compounds to maximize kinase inhibition with the variety of protocols used to
      assess the role of PI3 kinase in biological systems, or for achieving optimal
      therapeutic effects in vivo . In addition, the slow self-activation of WmC20
      derivatives provides a mechanism that can be exploited to obtain kinase
      inhibitors endowed with physical and pharmacokinetic properties far different
      from man-made kinase inhibitors because they do not bind to kinase active sites.

PMID- 18630896
TI  - Structure-based development of novel adenylyl cyclase inhibitors.
AB  - In mammals, the second messenger cAMP is synthesized by a family of transmembrane
      isoforms (tmACs) and one known cytoplasmic enzyme, "soluble" adenylyl cyclase
      (sAC). Understanding the individual contributions of these families to cAMP
      signaling requires tools which can distinguish them. Here, we describe the
      structure-based development of isoform discriminating AC inhibitors. Docking
      calculations using a library of small molecules with the crystal structure of a
      sAC homologue complexed with the noncompetitive inhibitor catechol estrogen
      identified two novel inhibitors, 3,20-dioxopregn-4-en-21-yl4
      bromobenzenesulfonate (2) and 1,2,3,4,5,6,7,8,13,13,14,14-dodecachloro
      1,4,4a,4b,5,8,8a,12b-octahydro-11-sulfo-1,4:5,8-dimethanotriphenylene-10
      carboxylic acid (3). In vitro testing revealed that 3 defines a novel AC
      inhibitor scaffold with high affinity for human sAC and less inhibitory effect on
      mammalian tmACs. 2 also discriminates between sAC and tmACs, and it appears to
      simultaneously block the original binding pocket and a neighboring interaction
      site. Our results show that compounds exploiting the catechol estrogen binding
      site can produce potent, isoform discriminating AC inhibitors.

PMID- 18630897
TI  - Selective nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) inhibitors:
      nucleotide mimetics derived from uridine-5'-carboxamide.
AB  - Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases, subtypes 1, 2, 3, 8
      of NTPDases) dephosphorylate nucleoside tri- and diphosphates to the
      corresponding di- and monophosphates. In the present study we synthesized adenine
      and uracil nucleotide mimetics, in which the phosphate residues were replaced by
      phosphonic acid esters attached to the nucleoside at the 5'-position by amide
      linkers. Among the synthesized uridine derivatives, we identified the first
      potent and selective inhibitors of human NTPDase2. The most potent compound was
      19a (PSB-6426), which was a competitive inhibitor of NTPDase2 exhibiting a K i
      value of 8.2 microM and selectivity versus other NTPDases. It was inactive toward
      uracil nucleotide-activated P2Y 2, P2Y 4, and P2Y 6 receptor subtypes. Compound
      19a was chemically and metabolically highly stable. In contrast to the few known
      (unselective) NTPDase inhibitors, 19a is an uncharged molecule and may be
      perorally bioavailable. NTPDase2 inhibitors have potential as novel
      cardioprotective drugs for the treatment of stroke and for cancer therapy.

PMID- 18630898
TI  - 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of
      anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar
      structure-activity relationship profile.
AB  - A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2
      oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro
      , 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl- S
      DABOs, 6-8) is here described. The new compounds showed low micromolar to low
      nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1.
      Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in
      enzyme (wt and K103N, Y181I, and L100I mutated RTs) assays, compounds carrying an
      ethyl/ iso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety
      at C6 were the most potent derivatives, also characterized by low fold resistance
      ratio. Interestingly, the structure-activity relationship (SAR) data drawn from
      this DABO series are more related to HEPT than to DABO derivatives. These
      findings were at least in part rationalized by the description of a fair
      superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in
      both WT and Y181C RTs.

PMID- 18630899
TI  - Evolving interpretable structure-activity relationships. 1. Reduced graph
      queries.
AB  - A new machine learning method is presented for extracting interpretable structure
      activity relationships from screening data. The method is based on an
      evolutionary algorithm and reduced graphs and aims to evolve a reduced graph
      query (subgraph) that is present within the active compounds and absent from the
      inactives. The reduced graph representation enables heterogeneous compounds, such
      as those found in high-throughput screening data, to be captured in a single
      representation with the resulting query encoding structure-activity information
      in a form that is readily interpretable by a chemist. The application of the
      method is illustrated using data sets extracted from the well-known MDDR data set
      and GSK in-house screening data. Queries are evolved that are consistent with the
      known SARs, and they are also shown to be robust when applied to independent sets
      that were not used in training.

PMID- 18630900
TI  - Designed synthesis of new ortho-carborane derivatives: from mono- to
      polysubstituted frameworks.
AB  - The use of nucleophilic and electrophilic processes allow the designed synthesis
      of several B-iodinated derivatives of o-carborane. Because of the straightforward
      Pd-catalyzed conversion of B-I to B-C bond with Grignard reagents, such as
      methylMgBr and biPhenylMgBr, both, symmetrical 3,6-R 2-1,2- closo-C 2B 10H 10 and
      asymmetrical 3-I-6-Me-1,2- closo-C 2B 10H 10 could be obtained. Not only
      conventional reactions in solution have been studied but also a highly efficient,
      clean and fast solvent-free procedure has provided successful results to
      regioselectively produce B-iodinated o-carborane derivatives by a careful control
      of the reaction conditions. The high number of nonequivalent leaving groups in
      boron iodinated o-carborane derivatives opens the possibility through B-C
      coupling to materials with novel possibilities and to self-assembling due to the
      enhanced polarizability of the C-H bond.

PMID- 18630901
TI  - Mixed-ligand uranyl(V) beta-diketiminate/beta-diketonate complexes: synthesis and
      characterization.
AB  - The reaction of [UO 2(Ar 2nacnac)Cl] 2 [Ar 2nacnac = (2,6- (i)Pr 2C 6H
      3)NC(Me)CHC(Me)N(2,6- (i)Pr 2C 6H 3)] with Na(RC(O)CHC(O)R) (R = Me, Ph, CF 3) in
      tetrahydrofuran results in the formation of UO 2(Ar 2nacnac)(RC(O)CHC(O)R) (R =
      Me, 1; Ph, 2; CF 3, 3), which can be isolated in moderate yields. The structures
      of 1 and 2 have been confirmed by X-ray crystallography, while the solution redox
      properties of 1- 3 have been measured by cyclic voltammetry. Complexes 1- 3
      exhibit reduction features at -1.82, -1.59, and -1.39 V (vs Fc/Fc (+)),
      respectively, at a scan rate of 100 mV.s (-1). The decrease in the reduction
      potential follows the electron-withdrawing ability of each beta-diketonate
      ligand. Chemical reduction of 1 and 2 with Cp* 2Co in toluene yields [Cp* 2Co][UO
      2(Ar 2nacnac)(RC(O)CHC(O)R)] (R = Me, 4; Ph, 5), while reduction of 3 with Cp 2Co
      provides [Cp 2Co][UO 2(Ar 2nacnac)(CF 3C(O)CHC(O)CF 3)] ( 6). Complexes 4- 6 have
      been fully characterized, while the solid-state molecular structure of 5 has also
      been determined. In contrast to the clean reduction that occurs with Cp* 2Co,
      reduction of 1 with sodium ribbon, followed by cation exchange with [NEt 4]Cl,
      produces [NEt 4][UO 2(Ar 2nacnac)(H 2CC(O)CH(O)CMe)] ( 7) in modest yield. This
      product results from the formal loss of H (*) from a methyl group of the
      acetylacetonate ligand. Alternately, complex 7 can be synthesized by
      deprotonation of 1 with NaNTMS 2 in good yield.

PMID- 18630902
TI  - Oxidative addition of group 13 and 14 metal halides and Alkyls to Ga(DDP) (DDP =
      bulky bisimidinate).
AB  - The oxidative addition of a variety of group 13 and group 14 halides and alkyls R
      aMX to the mono valent group 13 bis-imidinate Ga(DDP) (DDP = 2-{(2,6-diisopropyl
      phenyl)amino}-4-{(2,6-diisopropylphenyl)imino}-2-pentene) is reported.
      Accordingly, the insertion of Ga(DDP) into the Ga-Me bond of GaMe 3 yield in the
      complexes [{(DDP)GaMe}GaMe 2] ( 1) and [{(DDP)GaMe} 2GaMe] ( 2), respectively,
      which show a temperature-dependent equilibrium between 1 at higher temperatures
      and 2 at lower temperatures. In the case of GaCl 3, the only isolable product is
      [{(DDP)GaCl} 2GaCl] ( 3). The related reaction of SnMe 2Cl 2 with Ga(DDP) yields
      the compound [Me 2Sn{ClGa(DDP)} 2] ( 4), whereas SnMe 4 behaves inert. In the
      case of SiCl 4, only the monoinsertion product [Cl 3Si{ClGa(DDP)}] ( 5) was
      observed. Finally, [(CH 3) 3C{ClGa(DDP)}] ( 6) is synthesized by insertion of
      Ga(DDP) into the C-Cl bond of ClC(CH 3) 3. All new compounds were fully
      characterized by elemental analysis, NMR-spectroscopy, and single-crystal X-ray
      diffraction analysis.

PMID- 18630903
TI  - Structures of silver pyrazolates in hydrocarbon solutions via vapor-pressure
      osmometry.
AB  - Molecular weights of {[3,5-(CF 3) 2Pz]Ag} 3, {[3-(C 3F 7),5-( t-Bu)Pz]Ag} 3, and
      {[3,5-( i-Pr) 2Pz]Ag} 3 at various solution concentrations have been investigated
      using vapor-pressure osmometry. Depending on the concentration, the trinuclear
      {[3,5-(CF 3) 2Pz]Ag} 3 either dissociates into mono- and dinuclear moieties or
      remains trinuclear or aggregates to hexanuclear species in toluene. In contrast,
      {[3-(C 3F 7),5-( t-Bu)Pz]Ag} 3, which has a bulky and relatively electron-rich
      pyrazolate, retains the trinuclear form even at low concentrations in toluene.
      Both {[3,5-(CF 3) 2Pz]Ag} 3 and {[3,5-( i-Pr) 2Pz]Ag} 3 adopt trinuclear
      structures in heptane at low concentrations. At higher concentrations, {[3,5-( i
      Pr) 2Pz]Ag} 3 forms hexanuclear species. The aggregation-segregation points are
      rather sharp and are reminiscent of the all-or-none character of phase
      transitions. Remarkably, at higher concentrations, the aggregation states of
      these silver pyrazolates are similar to those expected based on solid-state data.

PMID- 18630907
TI  - Platinum-catalyzed intramolecular vinylchalcogenation of alkynes with beta
      phenylchalcogeno conjugated amides.
AB  - Platinum-catalyzed intramolecular vinylthiolation and -selenation of internal
      alkynes with vinylchalcogenides 1 having a carbamoyl group on cis-beta-position
      of vinyl moiety was developed. The conjugated six-membered lactam framework 2 was
      constructed in high yields. Density functional theory calculations for alkyne
      insertion processes suggest seven-membered platinacycle 3 is a kinetically
      favored intermediate of this catalytic system.

PMID- 18630908
TI  - Effect of the phase states of self-assembled monolayers on pentacene growth and
      thin-film transistor characteristics.
AB  - To investigate the effects of the phase state (ordered or disordered) of self
      assembled monolayers (SAMs) on the growth mode of pentacene films and the
      performance of organic thin-film transistors (OTFTs), we deposited pentacene
      molecules on SAMs of octadecyltrichlorosilane (ODTS) with different alkyl-chain
      orientations at various substrate temperatures (30, 60, and 90 degrees C). We
      found that the SAM phase state played an important role in both cases. Pentacene
      films grown on relatively highly ordered SAMs were found to have a higher
      crystallinity and a better interconnectivity between the pentacene domains, which
      directly serves to enhance the field-effect mobility, than those grown on
      disordered SAMs. Furthermore, the differences in crystallinity and field-effect
      mobility between pentacene films grown on ordered and disordered substrates
      increased with increasing substrate temperature. These results can be possibly
      explained by (1) a quasi-epitaxy growth of the pentacene film on the ordered ODTS
      monolayer and (2) the temperature-dependent alkyl chain mobility of the ODTS
      monolayers.

PMID- 18630909
TI  - Acetal-derivatized dextran: an acid-responsive biodegradable material for
      therapeutic applications.
AB  - Dextran, a biocompatible, water-soluble polysaccharide, was modified at its
      hydroxyls with acetal moieties such that it became insoluble in water but freely
      soluble in common organic solvents enabling its use in the facile preparation of
      acid-sensitive microparticles. These particles degrade in a pH-dependent manner:
      FITC-dextran was released with a half-life at 37 degrees C of 10 h at pH 5.0
      compared to a half-life of approximately 15 days at pH 7.4. Both hydrophobic and
      hydrophilic cargoes were successfully loaded into these particles using single
      and double emulsion techniques, respectively. When used in a model vaccine
      application, particles loaded with the protein ovalbumin (OVA) increased the
      presentation of OVA-derived peptides to CD8+ T-cells 16-fold relative to OVA
      alone. Additionally, this dextran derivative was found to be nontoxic in
      preliminary in vitro cytotoxicity assays. Owing to its ease of preparation,
      processability, pH-sensitivity, and biocompatibility, this type of modified
      dextran should find use in numerous drug delivery applications.

PMID- 18630910
TI  - Identification of a gene cluster that directs putrebactin biosynthesis in
      Shewanella species: PubC catalyzes cyclodimerization of N-hydroxy-N
      succinylputrescine.
AB  - Putrebactin is a dihydroxamate iron chelator produced by the metabolically
      versatile marine bacterium Shewanella putrefaciens. It is a macrocyclic dimer of
      N-hydroxy-N-succinyl-putrescine (HSP) and is structurally related to
      desferrioxamine E, which is a macrocyclic trimer of N-hydroxy-N-succinyl
      cadaverine (HSC). We recently showed that DesD, a member of the NIS synthetase
      superfamily, catalyzes the key step in desferrioxamine E biosynthesis: ATP
      dependent trimerisation and macrocylization of HSC. Here we report identification
      of a conserved gene cluster in the sequenced genomes of several Shewanella
      species, including Shewanella putrefaciens, which is hypothesized to direct
      putrebactin biosynthesis from putrescine, succinyl-CoA and molecular oxygen. The
      pubC gene within this gene cluster encodes a protein with 65% similarity to DesD.
      We overexpressed pubC from Shewanella species MR-4 and MR-7 in E. coli. The
      resulting His6-PubC fusion proteins were purified by Ni-NTA affinity and gel
      filtration chromatography. The recombinant proteins were shown to catalyze ATP
      dependent cyclodimerization of HSP to form putrebactin. The uncyclized dimer of
      HSP pre-putrebactin was shown to be an intermediate in the conversion of two
      molecules of HSP to putrebactin. The data indicate that pre-putrebactin is
      converted to putrebactin via PubC-catalyzed activation of the carboxyl group by
      adenylation, followed by PubC-catalyzed nucleophilic attack of the amino group on
      the carbonyl carbon of the acyl adenylate. This mechanism for macrocycle
      formation is very different from the mechanism involved in the biosynthesis of
      many other macrocyclic natural products, where already-activated acyl thioesters
      are converted by thioesterase domains of polyketide synthases and nonribosomal
      peptide synthetases to macrocycles via covalent enzyme bound intermediates. The
      results of this study demonstrate that two closely related enzymes, PubC and
      DesD, catalyze specific cyclodimerization and cyclotrimerization reactions,
      respectively, of structurally similar substrates, raising intriguing questions
      regarding the molecular mechanism of specificity.

PMID- 18630911
TI  - NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation
      domain of VP16: structural similarities between VP16 and p53.
AB  - The Herpes Simplex Virion Protein 16 (VP16) activates transcription through a
      series of protein/protein interactions involving its highly acidic
      transactivation domain (TAD). The acidic TAD of VP16 (VP16TAD) has been shown to
      interact with several partner proteins both in vitro and in vivo, and many of
      these VP16 partners also bind the acidic TAD of the mammalian tumor suppressor
      protein p53. For example, the TADs of VP16 and p53 (p53TAD) both interact
      directly with the p62/Tfb1 (human/yeast) subunit of TFIIH, and this interaction
      correlates with their ability to activate both the initiation and elongation
      phase of transcription. In this manuscript, we use NMR spectroscopy, isothermal
      titration calorimetery (ITC) and site-directed mutagenesis studies to
      characterize the interaction between the VP16TAD and Tfb1. We identify a region
      within the carboxyl-terminal subdomain of the VP16TAD (VP16C) that has sequence
      similarity with p53TAD2 and binds Tfb1 with nanomolar affinity. We determine an
      NMR structure of a Tfb1/VP16C complex, which represents the first high-resolution
      structure of the VP16TAD in complex with a target protein. The structure
      demonstrates that like p53TAD2, VP16C forms a 9-residue alpha-helix in complex
      with Tfb1. Comparison of the VP16/Tfb1and p53/Tfb1 structures clearly
      demonstrates how the viral activator VP16C and p53TAD2 shares numerous aspects of
      binding to Tfb1. Despite the similarities, important differences are observed
      between the p53TAD2/Tfb1 and VP16C/Tfb1 complexes, and these differences
      demonstrate how selected activators such as p53 depend on phosphorylation events
      to selectively regulate transcription.

PMID- 18630912
TI  - Large exTTF-based dendrimers. Self-assembly and peripheral cooperative
      multiencapsulation of C60.
AB  - The convergent synthesis of large monodisperse dendrimers, up to the fourth
      generation, decorated in their periphery with pi-extended tetrathiafulvalene
      units is reported, and their redox and supramolecular properties are
      investigated. A number of experiments (MALDI-TOF, (1)H NMR at variable
      temperature and different concentration, DLS, AFM and SEM imaging) confirm the
      self-aggregation process of these dendrimers, despite the butterfly-like shape of
      the exTTF units, highly distorted from planarity, to form large supramolecular
      architectures in the gas phase, in solution, and on a mica surface. Dendrimers 5,
      9, and 12 host a number of C60 molecules to form segregated arrays of donor and
      acceptor units which could give rise to valuable materials useful for the
      preparation of optoelectronic devices. UV-vis titration experiments demonstrate
      that complexation of C60 occurs in a positive cooperative manner. Cyclic
      voltammetry experiments show that the peripheral exTTF units are involved in
      multioxidation processes. The self-diffusion coefficients (D) of the dendrimers
      reported herein and the previously reported exTTF (1) and tweezer (2) have been
      calculated from their chronoamperograms at different concentrations and by the
      Cottrell equation and, where possible, by PFG-NMR. The calculated values for D
      demonstrate the decrease of this magnitude with increasing dendrimer size.

PMID- 18630913
TI  - Structural and spectroscopic characterization of an electrophilic iron nitrido
      complex.
AB  - We have isolated and structurally characterized a terminal iron nitrido complex
      supported by a bulky tris(carbene)borate ligand. The electronic structure of this
      complex reveals that the a1 LUMO (formerly Fe(dz2)) is strongly stabilized by
      reduced antibonding interactions with the carbene sigma-donor ligands and
      configurational mixing (hybridization) with higher lying Fe 4s and 4p atomic
      orbitals. This unusual bonding interaction results in a low-lying Fe nitrido
      acceptor orbital (LUMO) that possesses electrophilic character. Reaction with
      PPh3 results in nitrogen atom transfer to the phosphine, supporting a reaction
      mechanism involving nucleophilic attack of the triphenylphosphine HOMO at the
      electrophilic LUMO of the iron nitrido complex.

PMID- 18630914
TI  - Solvent interactions and conformational choice in a core N-glycan segment: gas
      phase conformation of the central, branching trimannose unit and its singly
      hydrated complex.
AB  - The intrinsic conformational preferences and structures of the branched
      trimannoside, alpha-phenyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D
      mannopyranoside (which contains the same carbohydrates found in a key subunit of
      the core pentasaccharide in N-glycans) and its singly hydrated complex, have been
      investigated in the gas phase isolated at low temperature in a molecular beam
      expansion. Conformational assignments of their infrared ion dip spectra, based on
      comparisons between experiment and ONIOM (B3LYP/6-31+G(d):HF/6-31G(d)) and single
      point MP2 calculations have identified their preferred structures and relative
      energies. The unhydrated trimannoside populates a unique structure supported by
      two strong, central hydrogen bonds linking the central mannose unit (CM), and its
      two branches (3M and 6M) closely together, through a cooperative hydrogen-bonding
      network: OH4(CM)-->OH6(3M)-->OH6(6M). A closely bound structure is also retained
      in the singly hydrated oligosaccharide, with the water molecule bridging across
      the 3M and 6M branches to provide additional bonding. This structure contrasts
      sharply with the more open, entropically favored trimannoside structure
      determined in aqueous solution at 298 K. In principle this structure can be
      accessed from the isolated trimannoside structure by a simple conformational
      change, a twist about the alpha(1,3) glycosidic linkage, increasing the dihedral
      angle psi[C1(3M)-O3(3M)-C3(CM)-C2(CM)] from approximately 74 degrees to
      approximately 146 degrees to enable accommodation of a water molecule at the
      centrally bound site occupied by the hydroxymethyl group on the 3M ring and
      mediation of the water-linked hydrogen-bonded network: OH4(CM) -->OH(W)-
      >OH6(6M). The creation of a "water pocket" motif localized at the bisecting axis
      of the trimannoside is strikingly similar to the structure of more complex N
      glycans in water, suggesting perhaps a general role for the "bisecting" OH4 group
      in the central (CM) mannose unit.

PMID- 18630915
TI  - A simple approach to separate a mixture of homopropargylic and allenic alcohols.
AB  - A simple and practical approach to separate homopropargylic alcohol from allenic
      alcohol has been developed. It involves the formation of an insoluble silver
      acetylide species between silver nitrate and homopropargylic alcohol in aqueous
      acetone which can be separated from the allenic alcohol through a simple
      filtration. The homopropargylic alcohol can subsequently be recovered by
      hydrolysis with 1 N HCl. This protocol has been applied to the separation of a
      mixture of chiral homopropargylic and allenic alcohols in excellent yields with
      retention of absolute stereochemistry.

PMID- 18630916
TI  - Pi-stacking effect on levoglucosenone derived internal chiral auxiliaries. A case
      of complete enantioselectivity inversion on the Diels-Alder reaction.
AB  - Detailed quantum chemical calculations, experimental evidence, and NMR data
      rationalize the participation of pi-stacking interaction in the highly asymmetric
      Diels-Alder reaction using levoglucosenone derived internal chiral auxiliaries,
      including the appealing effect of inversion of the enantioselectivity by
      coordination of the substrate with Et 2AlCl.

PMID- 18630917
TI  - Ruthenium-catalyzed hydroarylations of methylenecyclopropanes: mild C-H bond
      functionalizations with conservation of cyclopropane rings.
AB  - Ring conservation was observed in the first catalytic intermolecular
      hydroarylation of methylenecyclopropanes via C-H bond functionalization, a
      remarkable reactivity mode for a transformation proceeding through
      (cyclopropylcarbinyl)metal intermediates.

PMID- 18630918
TI  - Efficient synthesis of sulfonyl azides from sulfonamides.
AB  - Triflyl azide serves as an efficient diazo transfer reagent in this first direct
      synthesis of sulfonyl azides from readily available and stable sulfonamides. The
      process is experimentally simple, mild, and high-yielding. Sulfonyl azides
      participate in various catalytic transformations providing rapid access to
      diversely functionalized sulfonamide derivatives in good yields.

PMID- 18630919
TI  - Sporulenes, heptaprenyl metabolites from Bacillus subtilis spores.
AB  - Sporulene, a C 35-terpenoid hydrocarbon with an unusual pentacyclic structure, is
      produced by Bacillus subtilis during sporulation.

PMID- 18630920
TI  - Aminoferrocene lithiation by boron trifluoride activation.
AB  - Lithiation of BF 3-complexed dimethylaminoferrocene occurs exclusively ortho to
      the dimethylamino group in the cyclopentadienyl ring providing structurally
      diverse products in 76-94% yield after electrophile quench. This method
      represents the first direct C2-lithiation of a monosubstituted aminoferrocene,
      offering rapid and complementary access to this class of compounds over
      procedures that utilize carbon- and sulfur-based directing groups and may serve
      as a prelude to an asymmetric process.

PMID- 18630921
TI  - 2,6-Diazaspiro[3.3]heptanes: synthesis and application in Pd-catalyzed aryl
      amination reactions.
AB  - A concise and scalable synthesis of a 2,6-diazaspiro[3.3]heptane building block
      is reported. The usefulness of this structural surrogate of piperazine is shown
      in arene amination reactions yielding a variety of N-Boc- N'-aryl-2,6
      diazaspiro[3.3]heptanes.

PMID- 18630922
TI  - A concise synthesis of the pentacyclic framework of cortistatins.
AB  - An efficient synthesis of the pentacyclic framework of cortistatins has been
      developed. The key strategy comprises assembly of the A- and the CD-ring
      fragments by Knoevenagel reaction, facile formation of the pyran ring via
      electrocyclization, and construction of the seven-membered B-ring by radical
      addition to an alpha,beta-unsaturated ketone.

PMID- 18630923
TI  - Highly Direct alpha-Selective Glycosylations of 3,4-O-Carbonate-Protected 2-Deoxy
      and 2,6-Dideoxythioglycosides by Preactivation Protocol.
AB  - A new efficient pre-activation method for the highly alpha-stereoselective
      glycosylation of 2-deoxysugars and 2,6-dideoxysugars has been developed using 2
      deoxy- and 2,6-dideoxythioglycosides as glycosyl donors. The approach allows a
      wide range of glycosyl acceptors and donors to be used; the alpha-selectivity is
      very good to excellent.

PMID- 18630924
TI  - A highly diastereo- and enantioselective synthesis of multisubstituted
      cyclopentanes with four chiral carbons by the organocatalytic domino Michael
      Henry reaction.
AB  - Highly functionalized cyclopentanes with four stereogenic carbons including two
      quaternary stereocenters have been synthesized in excellent yields (90-95%) with
      complete diastereoselectivities and excellent enantioselectivities (88-96% ee) by
      the organocatalyzed asymmetric domino Michael-Henry reaction.

PMID- 18630925
TI  - Diastereodivergent aldol reactions of beta-alkoxy ethyl ketones: modular access
      to (1,4)-syn and -anti polypropionates.
AB  - Asymmetric substrate-controlled aldol reactions of ethyl ketones of type 4 with
      aldehyde 3 are reported. Modular access to all possible syn- and anti-aldol
      products was obtained by careful choice of reaction conditions. To achieve good
      selectivities in this diastereodivergent approach, selection of the protective
      group on the beta-oxygen of the enolate (R (2)) was of critical importance.

PMID- 18630926
TI  - A rigid molecular balance for measuring face-to-face arene-arene interactions.
AB  - A new molecular balance was developed to measure face-to-face arene-arene
      interactions. The balance adopts distinct folded and unfolded conformations due
      to restricted rotation about a C aryl-N imide bond. In the folded conformer, the
      rigid bicyclic framework enforces an offset face-to-face geometry to the
      exclusion of edge-to-face geometries, which was verified by X-ray
      crystallography. Measurement of the folded to unfolded ratio yields accurate
      values for the arene-arene interaction in a range of different solvents.

PMID- 18630928
TI  - Effects of metal nanoparticles on the secondary ion yields of a model alkane
      molecule upon atomic and polyatomic projectiles in secondary ion mass
      spectrometry.
AB  - A model alkane molecule, triacontane, is used to assess the effects of condensed
      gold and silver nanoparticles on the molecular ion yields upon atomic (Ga(+) and
      In(+)) and polyatomic (C60(+) and Bi3(+)) ion bombardment in metal-assisted
      secondary ion mass spectrometry (MetA-SIMS). Molecular films spin-coated on
      silicon were metallized using a sputter-coater system, in order to deposit
      controlled quantities of gold and silver on the surface (from 0 to 15 nm
      equivalent thickness). The effects of gold and silver islets condensed on
      triacontane are also compared to the situation of thin triacontane overlayers on
      metallic substrates (gold and silver). The results focus primarily on the
      measured yields of quasi-molecular ions, such as (M - H)(+) and (2M - 2H)(+), and
      metal-cationized molecules, such as (M + Au)(+) and (M + Ag)(+), as a function of
      the quantity of metal on the surface. They confirm the absence of a simple rule
      to explain the secondary ion yield improvement in MetA-SIMS. The behavior is
      strongly dependent on the specific projectile/metal couple used for the
      experiment. Under atomic bombardment (Ga(+), In(+)), the characteristic ion
      yields an increase with the gold dose up to approximately 6 nm equivalent
      thickness. The yield enhancement factor between gold-metallized and pristine
      samples can be as large as approximately 70 (for (M - H)(+) under Ga(+)
      bombardment; 10 nm of Au). In contrast, with cluster projectiles such as Bi3(+)
      and C60(+), the presence of gold and silver leads to a dramatic molecular ion
      yield decrease. Cluster projectiles prove to be beneficial for triacontane
      overlayers spin-coated on silicon or metal substrates (Au, Ag) but not in the
      situation of MetA-SIMS. The fundamental difference of behavior between atomic and
      cluster primary ions is tentatively explained by arguments involving the
      different energy deposition mechanisms of these projectiles. Our results also
      show that Au and Ag nanoparticles do not induce the same behavior in MetA-SIMS of
      triacontane. The microstructures of the metallized layers are also different.
      While metallic substrates provide higher yields than metal islet overlayers in
      the case of silver, whatever the projectile used, the situation is reversed with
      gold.

PMID- 18630929
TI  - Gravimetric approach to the standard addition method in instrumental analysis. 1.
AB  - A mathematical formulation for a gravimetric approach to the univariate standard
      addition method (SAM) is presented that has general applicability for both
      liquids and solids. Using gravimetry rather than volumetry reduces the
      preparation time, increases design flexibility, and makes increased accuracy
      possible. SAM has most often been used with analytes in aqueous solutions that
      are aspirated into flames or plasmas and determined by absorption, emission, or
      mass spectrometric techniques. The formulation presented here shows that the
      method can also be applied to complex matrixes, such as distillate and residual
      fuel oils, using techniques such as X-ray fluorescence (XRF) or combustion
      combined with atomic fluorescence or absorption. These techniques, which can be
      subject to matrix-induced interferences, could realize the same benefits that
      have been demonstrated for dilute aqueous solutions.

PMID- 18630930
TI  - The nitrite anion binds to human hemoglobin via the uncommon O-nitrito mode.
AB  - The nitrite anion is known to oxidize and degrade hemoglobin (Hb). Recent
      literature reports suggest a nitrite reductase activity for Hb, converting
      nitrite into nitric oxide. Surprisingly, no structural information about Hb
      nitrite interactions has been reported. We have determined the crystal structure
      of the ferric Hb-nitrite complex at 1.80 A resolution. The nitrite ligand adopts
      the uncommon O-nitrito binding mode. In addition, the nitrito conformations in
      the alpha and beta subunits are different, reflecting subtle effects of the
      distal His in orienting the nitrite ligand in the O-nitrito binding mode.

PMID- 18630932
TI  - Controlled plasmonic nanostructures for surface-enhanced spectroscopy and
      sensing.
AB  - After its discovery more than 30 years ago, surface-enhanced Raman spectroscopy
      (SERS) was expected to have major impact as a sensitive analytical technique and
      tool for fundamental studies of surface species. Unfortunately, the lack of
      reliable and reproducible fabrication methods limited its applicability. In
      recent years, SERS has enjoyed a renaissance, and there is renewed interest in
      both the fundamentals and applications of SERS. New techniques for
      nanofabrication, the design of substrates that maximize the electromagnetic
      enhancement, and the discovery of single-molecule SERS are driving the resurgence
      of this field. This Account highlights our group's recent work on SERS.
      Initially, we discuss SERS substrates that have shown proven reproducibility,
      stability, and large field enhancement. These substrates enable many analytical
      applications, such as anthrax detection, chemical warfare agent stimulant
      detection, and in vitro and in vivo glucose sensing. We then turn to a detailed
      study of the wavelength and distance dependence of SERS, which further illustrate
      predictions obtained from the electromagnetic enhancement mechanism. Last, an
      isotopic labeling technique applied to the rhodamine 6G (R6G)/silver system
      serves as an additional proof of the existence of single-molecule SERS and
      explores the dynamical features of this process. This work, in conjunction with
      theoretical calculations, allows us to comment on the possible role of charge
      transfer in the R6G/silver system.

PMID- 18630931
TI  - Arsenic trioxide impairs spermatogenesis via reducing gene expression levels in
      testosterone synthesis pathway.
AB  - Arsenic trioxide (As2O3) has recently received a great deal of attention because
      of its capacity to cause complete remission of acute promyelocytic leukemia
      (APL). To evaluate possible toxicity on the male reproductive system during
      arsenic therapy, male mice were used as a model. Outbred mice (ICR/CD1 and S-W, 6
      weeks old) were subcutaneously administered As2O3 continuously for 5 days, with a
      2-day interval, for a period of 3 weeks. As2O3 doses were 0, 0.15, 0.3, 1.5, and
      3.0 mg/kg of body weight, respectively. No mice died in any dosage group. Our
      data showed no significant changes in food consumption or in the weight of the
      body, liver, testis, or epididymis after As2O3 treatment. Using histological
      observation to identify the stages of seminiferous tubules, we showed that As2O3
      treatment resulted in the inhibition of spermatogenesis. The frequency of mature
      seminiferous tubules (stages VII and VIII) was markedly decreased after As2O3
      treatment. A significant decrease in sperm motility and viability also was found
      with computer-assisted sperm analysis (CASA) and a SYBR14/PI staining assay.
      Using an enzyme-linked immunosorbent assay (ELISA), we found a significant
      decrease in levels of plasma luteinizing hormone (LH) at a dose of 3.0 mg/kg body
      weight. No significant difference was found in plasma follicle-stimulating
      hormone (FSH) in all dosages. A significant decrease was found in plasma
      testosterone in all dosages, but no difference in intratesticular testosterone,
      with the exception of As2O3 at a dose of 3.0 mg/kg body weight. Moreover, there
      was a significant decrease in the levels of mRNA involved in testicular
      testosterone synthesis, cytochrome P450 side chain cleavage (P450scc), 3beta
      hydroxysteroid dehydrogenase (3beta-HSD), and cytochrome P450 17-alpha
      hydroxylase/C17-20 lyase (Cyp17). The use of immunohistological observation
      showed no obvious difference in the testosterone level of Leydig cells of mice
      treated with As2O3 at doses of 0.3 and 1.5 mg/kg body weight. We concluded that
      As2O3 treatment caused damage to sperm mobility and viability. As2O3 treatment
      disturbed spermatogenesis via reducing gene expression of the key enzymes in
      testosterone synthesis.

PMID- 18630933
TI  - A hydrogen bond surrogate approach for stabilization of short peptide sequences
      in alpha-helical conformation.
AB  - Alpha-helices constitute the largest class of protein secondary structures and
      play a major role in mediating protein-protein interactions. Development of
      stable mimics of short alpha-helices would be invaluable for inhibition of
      protein-protein interactions. This Account describes our efforts in developing a
      general approach for constraining short peptides in alpha-helical conformations
      by a main-chain hydrogen bond surrogate (HBS) strategy. The HBS alpha-helices
      feature a carbon-carbon bond derived from a ring-closing metathesis reaction in
      place of an N-terminal intramolecular hydrogen bond between the peptide i and i +
      4 residues. Our approach is centered on the helix-coil transition theory in
      peptides, which suggests that the energetically demanding organization of three
      consecutive amino acids into the helical orientation inherently limits the
      stability of short alpha-helices. The HBS method affords preorganized alpha-turns
      to overcome this intrinsic nucleation barrier and initiate helix formation. The
      HBS approach is an attractive strategy for generation of ligands for protein
      receptors because placement of the cross-link on the inside of the helix does not
      block solvent-exposed molecular recognition surfaces of the molecule. Our
      metathesis-based synthetic strategy utilizes standard Fmoc solid phase peptide
      synthesis methodology, resins, and reagents and provides HBS helices in
      sufficient amounts for subsequent biophysical and biological analyses. Extensive
      conformational analysis of HBS alpha-helices with 2D NMR, circular dichroism
      spectroscopies and X-ray crystallography confirms the alpha-helical structure in
      these compounds. The crystal structure indicates that all i and i + 4 C=O and NH
      hydrogen-bonding partners fall within distances and angles expected for a fully
      hydrogen-bonded alpha-helix. The backbone conformation of HBS alpha-helix in the
      crystal structure superimposes with an rms difference of 0.75 A onto the backbone
      conformation of a model alpha-helix. Significantly, the backbone torsion angles
      for the HBS helix residues fall within the range expected for a canonical alpha
      helix. Thermal and chemical denaturation studies suggest that the HBS approach
      provides exceptionally stable alpha-helices from a variety of short sequences,
      which retain their helical conformation in aqueous buffers at exceptionally high
      temperatures. The high degree of thermal stability observed for HBS helices is
      consistent with the theoretical predictions for a nucleated helix. The HBS
      approach was devised to afford internally constrained helices so that the
      molecular recognition surface of the helix and its protein binding properties are
      not compromised by the constraining moiety. Notably, our preliminary studies
      illustrate that HBS helices can target their expected protein receptors with high
      affinity.

PMID- 18630934
TI  - Field gradients can control the alignment of nanorods.
AB  - This work is motivated by the unexpected experimental observation that field
      gradients can control the alignment of nonmagnetic nanorods immersed inside
      magnetic fluids. In the presence of local field gradients, nanorods were observed
      to align perpendicular to the external field at low field strengths, but parallel
      to the external field at high field strengths. The switching behavior results
      from the competition between a preference to align with the external field
      (orientational potential energy) and preference to move into regions of minimum
      magnetic field (positional potential energy). A theoretical model is developed to
      explain this experimental behavior by investigating the statistics of nanorod
      alignment as a function of both the external uniform magnetic field strength and
      the local magnetic field variation above a periodic array of micromagnets.
      Computational phase diagrams are developed which indicate that the relative
      population of nanorods in parallel and perpendicular states can be adjusted
      through several control parameters. However, an energy barrier to rotation was
      discovered to influence the rate kinetics and restrict the utility of this
      assembly technique to nanorods which are slightly shorter than the micromagnet
      length. Experimental results concerning the orientation of nanorods inside
      magnetic fluid are also presented and shown to be in strong agreement with the
      theoretical work.

PMID- 18630935
TI  - Response of nanoparticle-based one-dimensional photonic crystals to ambient vapor
      pressure.
AB  - Herein we report an analysis of the variation of the optical properties of
      different nanoparticle-based one-dimensional photonic crystal architectures
      versus changes in the ambient vapor pressure. Gradual shift of the optical
      response provides us with information on the sorption properties of these
      structures and allow us to measure precise adsorption isotherms of these porous
      multilayers. The potential of nanoparticle-based one-dimensional photonic
      crystals as base materials for optical sensing devices is demonstrated in this
      way.

PMID- 18630936
TI  - Physical state of poorly water soluble therapeutic molecules loaded into SBA-15
      ordered mesoporous silica carriers: a case study with itraconazole and ibuprofen.
AB  - The ordered mesoporous silica material SBA-15 was loaded with the model drugs
      itraconazole and ibuprofen using three different procedures: (i) adsorption from
      solution, (ii) incipient wetness impregnation, and (iii) heating of a mixture of
      drug and SBA-15 powder. The location of the drug molecules in the SBA-15
      particles and molecular interactions were investigated using nitrogen adsorption,
      TGA, DSC, DRS UV-vis, and XPS. The in vitro release of hydrophobic model drugs
      was evaluated in an aqueous environment simulating gastric fluid. The
      effectiveness of the loading method was found to be strongly compound dependent.
      Incipient wetness impregnation using a concentrated itraconazole solution in
      dichloromethane followed by solvent evaporation was most efficient for dispersing
      itraconazole in SBA-15. The itraconazole molecules were located on the mesopore
      walls and inside micropores of the mesopore walls. When SBA-15 was loaded by
      slurrying it in a diluted itraconazole solution from which the solvent was
      evaporated, the itraconazole molecules ended up in the mesopores that they
      plugged locally. At a loading of 30 wt %, itraconazole exhibited intermolecular
      interactions inside the mesopores revealed by UV spectroscopy and endothermic
      events traced with DSC. The physical mixing of itraconazole and SBA-15 powder
      followed by heating above the itraconazole melting temperature resulted in
      formulations in which glassy itraconazole particles were deposited externally on
      the SBA-15 particles. Loading with ibuprofen was successful with each of the
      three loading procedures. Ibuprofen preferably is positioned inside the
      micropores. In vitro release experiments showed fast release kinetics provided
      the drug molecules were evenly deposited over the mesoporous surface.

PMID- 18630937
TI  - Surface design of carbon nanotubes for optimizing the adsorption and
      electrochemical response of analytes.
AB  - Carbon nanotubes (CNTs) from different sources were dissolved in water with high
      solubility by Congo red (CR) via strong noncovalent pi-stacking interactions. The
      resulting CNTs were capable of forming uniform, compact, stable films on various
      substrates. This provided a chance to explore the relationship between the
      surface property of CNTs and the adsorptive behavior of analytes on CNTs without
      considering the influence of film structures or free additives. Electrochemical
      behaviors of several small biomolecules and glucose oxidase (GOD) on various CR
      functionalized CNT films were examined. The results showed that both the
      hydrophobic structural defect sites and the hydrophilic oxygen-containing groups
      were the electroactive sites of CNTs, which was further proven by UV-vis and FTIR
      spectra. Moreover, the surface properties of CNTs could be conveniently designed
      by simple pretreatments for optimizing the adsorption and the electrochemical
      response of analytes. For instance, the hydrophobic defect sites created during
      the growth or the workup of CNTs were favorable to the adsorption and the
      electrochemical response of hydrophobic analytes, whereas the hydrophilic oxygen
      containing groups produced by acid treatment facilitated the stable adsorption
      and the direct electrochemistry of redox proteins.

PMID- 18630938
TI  - Adsorption kinetics of organophosphonic acids on plasma-modified oxide-covered
      aluminum surfaces.
AB  - Tailoring of oxide chemistry on aluminum by means of low-pressure water and argon
      plasma surface modification was performed to influence the kinetics of the self
      assembly process of octadecylphosphonic acid monolayers. The plasma-induced
      surface chemistry was studied by in situ FTIR reflection-absorption spectroscopy
      (IRRAS). Ex situ IRRAS and X-ray photoelectron spectroscopy were applied for the
      analysis of the adsorbed self-assembled monolayers. The plasma-induced variation
      of the hydroxide to oxide ratio led to different adsorption kinetics of the
      phosphonic acid from dilute ethanol solutions as measured by means of a quartz
      crystal microbalance. Water plasma treatment caused a significant increase in the
      density of surface hydroxyl groups in comparison to that of the argon-plasma
      treated surface. The hydroxyl-rich surface led to significantly accelerated
      adsorption kinetics of the phosphonic acid with a time of monolayer formation of
      less than 1 min. On the contrary, decreasing the surface hydroxyl density slowed
      the adsorption kinetics.

PMID- 18630940
TI  - Chemically reactive derivatives of gramicidin A for developing ion channel-based
      nanoprobes.
AB  - Ion channel-forming peptides and proteins offer tremendous opportunities for
      fundamental and applied studies of function on individual molecules. An ongoing
      challenge in ion channel research is the lack of simple and accessible synthetic
      methods to engineer pores with tailored chemical and physical properties. This
      paper describes a practical synthetic route to rapidly generate C-terminally
      modified derivatives of gramicidin A (gA), an ion channel-forming peptide,
      through the use of two chemically reactive gA-based building blocks. These amine-
      and azide-containing building blocks can react readily with typical substrates
      for amidation and 1,3-dipolar cycloaddition ("click") reactions to present
      molecules with desired structure and functionality near the opening of a gA pore.
      These derivatives of gA are stable under typical aqueous conditions for ion
      channel recordings and retain characteristic single ion channel conductance
      properties in planar lipid bilayers. Additionally, the synthetic methods
      described here afford useful quantities of these gA derivatives in good purity
      and yield with minimal purification. We demonstrate that derivatives of gA can be
      used for studying, in situ, a change in conductance through a channel upon
      performing a "click" reaction on an azide moiety attached to the gA pore. We also
      demonstrate that these gA-based building blocks can be used to construct sensors
      for the recognition of specific protein-ligand binding interactions in solution.
      This widely accessible, enabling synthetic methodology represents a powerful new
      tool to study relationships between chemical structure and function on the single
      molecule level.

PMID- 18630939
TI  - Covalent modifications of antitetanus F(ab')2 fragments with natural and
      synthetic polyamines and their effects on the antibody endocytosis in cultured
      HL60 cells.
AB  - For antibody therapeutics to succeed when intracellular target molecules are
      involved, a strategy must be applied to increase the delivery of antibodies into
      cells to reach their targets. Antibody cationization by chemical conjugation of a
      polyamine could be one such strategy. Both natural polyamines with increasing net
      charge valencies (putrescine, PUT; spermidine, SPD; and spermine, SPM) and a
      synthetic polyamine (hexamethylenediamine, HMD) can be used to cationize
      antibodies, but no comparison of the respective effects of these polyamines on
      intracellular delivery of antibodies has been performed yet. This study describes
      the covalent modification of antitetanus F(ab') 2 with these four polyamines
      using different reaction conditions, and compares the effects of these
      modifications on antibody interaction with cultured HL60 cells. The cationized
      antibodies retained > or =80% of the binding activity of the unmodified F(ab') 2
      with regard to tetanus toxin, as measured by an antigen-binding capture enzyme
      immunoassay. This same method was used to quantify the amount of cell-associated
      F(ab') 2 following incubation with HL60 cells. Cationization was shown to enhance
      cell interaction of the F(ab') 2 : the higher the number of coupled polyamine
      molecules, the greater the amount of antibody associated with the cells.
      Moreover, coupling the F(ab') 2 to the SPD and SPM polyamines had greater effect
      on cell interaction than coupling the F(ab') 2 to the PUT and HMD diamines.
      Internalization of the cationized antibodies by the HL60 cells was demonstrated
      by confocal microscopy. This technique also showed that SPD and SPM were more
      effective than PUT and HMD in terms of intracellular delivery of the F(ab') 2 .
      It follows from all these results that electrostatic interaction involving charge
      density plays a predominant role in the endocytic transport mechanism of the
      F(ab') 2 modified with these polyamines. However, coupling the F(ab') 2 to SPM
      and SPD yielded the same maximum effects in terms of cell interaction, although
      coupling SPM was expected to increase the antibody net charge valency more than
      coupling SPD. This finding suggests that the effective global charge for the cell
      interaction and uptake of polyamine-modified antibodies does not simply
      correspond to the addition of the ionizable amine functions on the coupled
      polyamines, and that other factors may come into play.

PMID- 18630941
TI  - Specific phosphopeptide enrichment with immobilized titanium ion affinity
      chromatography adsorbent for phosphoproteome analysis.
AB  - The elucidation of protein post-translational modifications, such as
      phosphorylation, remains a challenging analytical task for proteomic studies.
      Since many of the proteins targeted for phosphorylation are low in abundance and
      phosphorylation is typically substoichiometric, a prerequisite for their
      identification is the specific enrichment of phosphopeptide prior to mass
      spectrometric analysis. Here, we presented a new method termed as immobilized
      titanium ion affinity chromatography (Ti (4+)-IMAC) for enriching
      phosphopeptides. A phosphate polymer, which was prepared by direct polymerization
      of monomers containing phosphate groups, was applied to immobilize Ti (4+)
      through the chelating interaction between phosphate groups on the polymer and Ti
      (4+). The resulting Ti (4+)-IMAC resin specifically isolates phosphopeptides from
      a digest mixture of standard phosphoproteins and nonphosphoprotein (BSA) in a
      ratio as low as 1:500. Ti (4+)-IMAC was further applied for phosphoproteome
      analysis of mouse liver. We also compared Ti (4+)-IMAC to other enrichment
      methods including Fe (3+)-IMAC, Zr (4+)-IMAC, TiO 2 and ZrO 2, and demonstrate
      superior selectivity and efficiency of Ti (4+)-IMAC for the isolation and
      enrichment of phosphopeptides. The high specificity and efficiency of
      phosphopeptide enrichment by Ti (4+)-IMAC mainly resulted from the flexibility of
      immobilized titanium ion with spacer arm linked to polymer beads as well as the
      specific interaction between immobilized titanium ion and phosphate group on
      phosphopeptides.

PMID- 18630942
TI  - Proteomics analysis of kojic acid treated A375 human malignant melanoma cells.
AB  - Although the toxicogenomics of kojic acid treated A375 human malignant melanoma
      cells has been elucidated, the proteomics of cellular response is still poorly
      understood. We performed proteomic analysis to investigate the anticancer effect
      of kojic acid on protein expression profile in A375 cells. A375 cells were
      treated with kojic acid at 8 microg/mL for 24, 48, and 72 h. With the use of 2-D
      PAGE and MALDI-Q-TOF MS and MS/MS analyses, proteomic profiles of A375 cells
      between control and kojic acid treatment were compared, and 30 differentially
      expressed proteins, containing 2 up-regulated proteins and 28 down-regulated
      proteins, were identified. Among these proteins, 17 isoforms of 5 identical
      proteins were observed and 11 chaperone proteins showed the high proportion of
      protein spots with 36.7% of total proteins. Bioinformatic tools were used to
      search for protein function and prediction of protein interaction. Sixteen
      differentially expressed proteins exhibited interaction network linked to the
      downstream regulations of p53 tumor suppressor and cell apoptosis, which may lead
      to suppress the melanogenesis and tumorigenesis of kojic acid treated A375 cells.
      In addition, GRP75, VIME and 2AAA were validated by Western blot analysis,
      whereas GRP75, 2AAA, HS90B, ENPL and KPYM were validated by RT-PCR. Therefore,
      these proteins play the important roles in cancer progression and may be
      potential biomarkers that are useful for diagnostic and therapeutic applications
      of malignant melanoma cancer.

PMID- 18630944
TI  - Application of proteomic tools to detect the nonspecificity of a polyclonal
      antibody against lipoprotein lipase.
AB  - Specific antibodies are essential tools for studying proteins. P66 is a chicken
      polyclonal antibody raised against bovine lipoprotein lipase (LPL) that has been
      used in earlier studies. Here, we developed a two-dimensional (2D) Western blot
      with reducing gels, using commercial bovine LPL (53 kDa) as a standard and P66
      for detection. Our results revealed incomplete purification of commercial LPL and
      nonspecificity of P66, both undetectable in one-dimensional analysis.
      Antithrombin III (ATIII) was identified as both a major contaminant in commercial
      LPL and a cross-reacting protein with P66. Although LPL purification methods were
      presumably designed to eliminate ATIII, here we demonstrate that some procedures
      fell short of this objective and thus led to the production of a nonspecific
      antibody. Our results define 2D electrophoresis/Western blot and mass
      spectrometric protein identification as the most reliable procedure for
      validating LPL purity and the specificity of antibodies against this enzyme.

PMID- 18630943
TI  - DirecTag: accurate sequence tags from peptide MS/MS through statistical scoring.
AB  - In shotgun proteomics, tandem mass spectra of peptides are typically identified
      through database search algorithms such as Sequest. We have developed DirecTag,
      an open-source algorithm to infer partial sequence tags directly from observed
      fragment ions. This algorithm is unique in its implementation of three separate
      scoring systems to evaluate each tag on the basis of peak intensity, m/ z
      fidelity, and complementarity. In data sets from several types of mass
      spectrometers, DirecTag reproducibly exceeded the accuracy and speed of InsPecT
      and GutenTag, two previously published algorithms for this purpose. The source
      code and binaries for DirecTag are available from
      http://fenchurch.mc.vanderbilt.edu.

PMID- 18630945
TI  - The 140-GHz (D-band) saturation transfer electron paramagnetic resonance studies
      of macromolecular dynamics in conducting polymers.
AB  - The high-field/high-frequency (5 T, 140 GHz) saturation transfer electron
      paramagnetic resonance (ST-EPR) method was used for the study of superslow
      librational macromolecular dynamics in various conducting polymers. It was shown
      that the increase of the electron precession frequency allows separate
      determination of spin relaxation and dynamics differently affecting effective ST
      EPR spectra. Higher microwave frequency increases significantly the spectral
      resolution of the method and its sensitivity to the anisotropic macromolecular
      motion in conducting polymers. This broadens the interval of correlation time
      measured, thereby extending the slow-motion limit for ST-EPR by at least 2 orders
      of magnitude compared with convenient waveband EPR.

PMID- 18630946
TI  - Structure of synthetic transmembrane lipid membranes at the solid/liquid
      interface studied by specular X-ray reflectivity.
AB  - We fabricated a new class of supported membranes based on monolayers of
      artificial bola (transmembrane) lipids. The lipids used in this study are
      symmetric bola lipids with two phosphocholine head groups, which resemble natural
      archaea lipids. To prevent bending of the hydrocarbon chains, stiff triple bonds
      are inserted in the middle of the hydrocarbon cores. The formation of homogeneous
      "monolayers" of transmembrane lipids over macroscopic areas can be monitored with
      fluorescence microscopy. Structures of such supported monolayers in bulk water
      were characterized with specular X-ray reflectivity using high energy X-ray
      radiation, which guarantees a high transmission through bulk water. Here, the
      vertical structure of single monolayers could be resolved from reconstructed
      electron density profiles. To verify the structural model suggested by the
      specular reflectivity, we also performed small- and wide-angle X-ray scattering
      of transmembrane lipid suspensions. The wide-angle patterns reflect a distorted
      chain-chain correlation, while the small-angle scattering allowed us to model an
      electron density profile which is consistent with the profile calculated from
      specular reflectivity.

PMID- 18630947
TI  - DFT based Monte Carlo simulations of poly(9,9-dialkylfluorene-2,7-diyl) polymers
      in solution.
AB  - The dilute solution properties of poly(9,9-dihexylfluorene-2,7-diyl) (PDHF) were
      studied by coupled SEC/light scattering and MALDI-TOF over a large molecular
      weight (MW) span ranging from PDHF oligomers (1-8-mer) to high MW polymer. The
      results were compared with Monte Carlo simulations based on realistic PDHF models
      obtained from X-ray data and density functional theory (DFT) calculations and
      with a DFT based Kratky-Porod-Benoit-Doty (KPBD) worm-like chain. The simulations
      called "selective random walk" (SRW) and the corresponding "selective self
      avoiding random walk" (SSAW) explicitly take into account the rotationally labile
      bonds between the fluorene units in that four distinct torsion angles (+/-37.5
      and +/-143 degrees) between the units are chosen randomly. The simulations better
      account than the KPBD model for the experimental data obtained by us and others
      for various poly(9,9-dialkylfluorene-2,7-diyl) polymers but still give somewhat
      larger values for the radii of gyration and hydrodynamic volumes. The torsion
      angle selectivity of the SRW and SSAW simulations predict long chain sections
      punctuated by sudden sharp loops.

PMID- 18630948
TI  - Thermodynamic investigation of the redox properties for ceria-hafnia, ceria
      terbia, and ceria-praseodymia solid solutions.
AB  - Ceria-hafnia, ceria-terbia, and ceria-praseodymia solid solutions were prepared
      by the citric-acid (Pechini) method and characterized using X-ray diffraction
      (XRD) for structure and coulometric titration for redox thermodynamics. Following
      calcination at 973 K, XRD showed that both Ce(0.5)Hf(0.5)O2 and Ce(0.8)Hf(0.2)O2
      exist as single-phase solid solutions and that the lattice parameters of the
      cubic fluorite structures shifted linearly with Hf content. Following calcination
      at 1323 K, Ce(0.8)Hf(0.2)O2 remained single phase but Ce(0.5)Hf(0.5)O2 separated
      into two phases with compositions of Ce(0.81)Hf(0.19)O2 and Ce(0.15)Hf(0.85)O2.
      At 973 K, oxidation isotherms for Ce(0.8)Hf(0.2)O2 and Ce(0.5)Hf(0.5)O2 were
      almost identical to oxidation isotherms for Ce(0.8)Zr(0.2)O2 and
      Ce(0.5)Zr(0.5)O2. Mixed oxides of ceria with terbia and praseodymia also formed
      single-phase fluorite structures, but each of the solid solutions was phase
      stable to calcination at 1323 K. The oxidation isotherms for the solid ceria
      terbia and ceria-praseodymia solutions were similar to what would be expected for
      physical mixtures of these oxides.

PMID- 18630949
TI  - Interaction between room temperature ionic liquid [bmim]BF4 and DNA investigated
      by electrochemical micromethod.
AB  - Ionic liquids (ILs) as a kind of novel green solvent are being widely used in
      various researches related to the life sciences and chemistry, which demands the
      knowledge of interaction between ILs and biomacromolecules. However, the almost
      completely inert optical, electric, thermal properties of ILs make it difficult
      to directly obtain information about the interactions. Herein, by using a
      hydrophilic ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate
      ([bmim]BF4) as a model, the electrostatic interaction between ILs and calf thymus
      DNA (ctDNA) was investigated by a surface electrochemical micromethod. A
      convenient and simple method was established to obtain the thermodynamic and
      kinetic information about the DNA-IL interaction only with microscale sample
      consumption. The quantitative thermodynamic and kinetic parameters about the
      interaction of [bmim]BF4 and ctDNA, such as the binding constant (K), the Gibbs
      energy of surface binding (DeltaGb), and the dissociation rate constant (k), were
      obtained for the first time.

PMID- 18630950
TI  - Binding to DNA purine base and structure-activity relationship of a series of
      structurally related Ru(II) antitumor complexes: a theoretical study.
AB  - The thermodynamics of the binding of a series of structurally related Ru(II)
      antitumor complexes, that is, alpha-[Ru(azpy)2Cl2] 1, beta-[Ru(azpy)2Cl2] 2,
      alpha-[Ru(azpy)(bpy)Cl2] 3, and cis-[Ru(bpy)2Cl2] 4 to DNA purine bases (gunine,
      adenine at N7 site) has been studied by using the DFT method. The binding of
      imine form of 9-methyladenine (9-MeAde) to the Ru(II) moiety in a didentate
      fashion via its N6 and N7 atoms was also considered. The geometrical structures
      of the DNA model base adducts were obtained at the B3LYP/(LanL2DZ + 6-31G(d))
      level in vacuo. The following exact single-point energy calculations were
      performed at the B3LYP/(LanL2DZ(f)+6-311+G(2d, 2p)) level both in vacuo and in
      aqueous solution using the COSMO model. The bond dissociation enthalpies and free
      energies, reaction enthalpies and free energies both in the gas phase and in
      aqueous solution for all considered Ru(II)-DNA model base adducts were obtained
      from the computations. The calculated bond dissociation enthalpies and free
      energies allow us to build a binding affinity order for the considered Ru(II)-DNA
      model base adducts. The theoretical results show that the guanine N7 is a
      preferred site for this series of complexes and support such an experimental fact
      that alpha-[Ru(azpy)(bpy)(9-EtGua)H2O](2+) (3-(9-EtGua)) is isomerized to alpha'
      [Ru(azpy)(bpy)(9-EtGua)H2O](2+) (3'-(9-EtGua)). On the basis of structural and
      thermodynamical characteristics, the possible structure-activity relationship was
      obtained, and the distinct difference in cytotoxicities of this series of
      structurally related antitumor complexes was explained theoretically.

PMID- 18630951
TI  - Orientational ordering of crystal domains in ionic liquid based mixtures.
AB  - By in situ observations using simultaneous X-ray diffraction and the DSC
      (differential scanning calorimetry) method, the effect of water, methanol,
      ethanol, and benzene on the crystallization has been observed in an ionic liquid
      (IL)-rich phase. The IL is a hydrophilic ionic liquid, N, N-diethyl-N-methyl-N-2
      methoxyethyl ammonium tetrafluoroborate, [DEME][BF4]. At a small amount of the
      above additional molecules in the IL, the conventional preferred orientation on
      the Debye rings was seen by the X-ray diffraction. At 0.9 mol % H2O, twinlike
      crystal domains develop extraordinary on the microdomains. By the "crystal-growth
      enhancement effect" at a slight amount of water, a composite domain structure,
      which consists of the large domain and the weakly orientated microdomains, is
      formed without internal strains. Above 2.9 mol % H2O, the domain structure,
      however, disappears completely. It is remarkable that, in a thermal cycling
      experiment using pure [DEME][BF4], the similar composite domain structure
      appeared. This is also caused by an uptake of a slight amount of water.

PMID- 18630952
TI  - Atomistic computer simulation and experimental study on the dynamics of the n
      cyanobiphenyls mesogenic series.
AB  - Several dynamic properties of the 4-n-alkyl-4'-cyanobiphenyls series ( nCB) with
      n=5, 6, 7, 8 have been studied by atomistic molecular dynamics (MD) simulations
      in the NVE ensemble adopting an ab initio derived force field (J. Phys. Chem. B
      2007, 111, 2130). For each homologue, at least two state points, in the nematic
      and in the isotropic phase, as determined from lengthy equilibration runs
      performed in the previous work, have been considered. More than 10 ns have been
      produced at each state point, allowing us to calculate single-molecule properties
      as the translational and rotational diffusion coefficients along the series. An
      oscillating behavior of the diffusion coefficients, similar to the observed odd
      even effect in static properties, has been predicted by MD. A good agreement with
      the results of purposely carried out (1)H NMR measurements is achieved, provided
      the MD values are increased by a factor that accounts for density overestimation.
      Spinning and tumbling rotational motions, monitored by calculating the rotational
      diffusion coefficients for all homologues in both phases, agree well with
      experimental data, at least for 5CB where NMR measures are reported. Collective
      properties, such as the isotropic shear viscosity and the rotational viscosity
      coefficient, have been computed for all homologues, and the MD values agree well
      with the experimental data reported in the literature. Finally, the origin of the
      odd-even effect, found for all the computed dynamic properties, is addressed.

PMID- 18630953
TI  - Study of the adsorption of organic molecules on transition metal exchanged
      zeolites via solid state NMR. Part 1: theoretical aspects.
AB  - A theoretical study is performed of the (1)H relaxation behavior of an organic
      molecule that is adsorbed in a zeolite exchanged with transition metal ions. An
      expression is derived for the spin-lattice and spin-spin relaxation rate constant
      of a uniform proton ensemble, while the occurrence of molecular exchange is taken
      into account. The influence is analyzed of an approach of a uniform proton
      ensemble toward the nearest neighboring paramagnetic ion system. It is shown that
      there exists a signal extinction effect, for which the critical distance was
      estimated.

PMID- 18630954
TI  - Electronic spectroscopic study of solvation of a ketocyanine dye in ternary
      solvent mixtures.
AB  - Solvation characteristics in ternary solvent mixtures have been studied by
      monitoring the solvent-sensitive electronic absorption band of a ketocyanine dye
      in two ternary solvent mixtures, water + ethanol + benzene and water + ethanol +
      cyclohexane, in which one of the pairs are partially miscible. Investigations
      have been done in a completely miscible region including the binodal curve. The
      maximum energy of absorption (E) of the solute in a ternary solvent mixture
      differs significantly from the mole fraction average of the E-values in the
      component solvents. Results in the corresponding binary solvent mixtures also
      show a deviation of the E-value from the mole fraction averaged E-values,
      indicating preferential solvation by a component solvent. The results in ternary
      solvent mixture have been explained in terms of a realistic model of solvation
      using the results on binary solvation.

PMID- 18630955
TI  - Time-resolved mapping of water diffusion coefficients in a working soft actuator
      device.
AB  - Diffusion-weighted imaging was employed to spatially map the distribution of the
      diffusion coefficient of water, D, in bare, water-soaked, Li(+)-exchanged, cast
      Nafion and in an ionic polymer-metal composite (IPMC) soft actuator element,
      prepared from this bare Nafion by impregnation with Pt electrodes. D was
      evaluated in two orthogonal directions: along one of the long dimensions of the
      sample (Dx) and through its thickness (Dz). D-maps of the IPMC element were
      obtained both in the absence of an applied potential and in situ during the
      application of a 3 V dc potential across the thickness of the sample. In the bare
      Nafion, D-maps showed uniform values of both Dx and Dz of about 6 x 10 (-10) m(2)
      s(-1). In the IPMC two effects were observed: (i) D at the electroded surfaces of
      the IPMC was higher than at the center of the sample; (ii) this difference was
      much greater in Dz than in Dx . Both effects were explained by the influence of
      the impregnated Pt electrodes on polymer structure. The D-maps in the
      electrochemical measurements showed high values of D (up to 8 x 10(-10) m(2) s(
      1)) at the cathode and low values (from 1 x 10(-10) m(2) s(-1)) at the anode.
      This was explained in terms of the effect on the Nafion nanostructure of the
      forced electro-migration of Li(H2O)x(+) species toward the cathode.

PMID- 18630956
TI  - Study of the adsorption of organic molecules on transition metal exchanged
      zeolites via solid state NMR. Part 2: adsorption of organic molecules on zeolite
      NaX, CaX, and CaCoX.
AB  - Literature [Denayer et al. Microporous Mesoporous Mater. 2007, 103, 1 and Denayer
      et al. Microporous Mesoporous Mater. 2007, 103, 11] shows that zeolite NaX
      exchanged with Ca(2+) and Co(2+) ions is able to remove cyclopentadiene (CPD)
      impurities from a 1-octene feed with high selectivity. In the present work, the
      adsorption of dicyclopentadiene (DCPD), CPD, 1-octene, and n-octane on zeolite X,
      exchanged with Ca(2+) and/or Co(2+) ions, has been investigated via (1)H magic
      angle spinning (MAS) NMR spectroscopy. The liquid adsorbate was dosed under inert
      atmosphere in an MAS rotor filled with dry adsorbent, at a pore filling degree of
      70%. Next, the evolution in time was recorded of the (1)H MAS NMR spectrum and
      the (1)H spin-lattice and spin-spin relaxation times of the adsorbed components.
      For the various adsorbate-adsorbent systems, a plot is made of the signal
      intensity versus the square root of the contact time. It is found that, over the
      considered time interval, Fickian diffusion takes place. On the basis of the
      change in time of the spin-lattice relaxation time, a transport diffusion
      coefficient ranging between 1 and 2 x 10(-15) m(2) x s(-1) is calculated.
      Moreover, there appear to be two sorption regimes, with different diffusivities.
      A comparison is made between the (1)H spin-lattice relaxation behavior of DCPD, 1
      octene, and n-octane, indicating that 1-octene and n-octane are located closer to
      the paramagnetic ions than DCPD. The average distance between the adsorbate
      molecules and the paramagnetic ions is derived from relaxometric data. By
      analyzing the chemical shifts of the resonance lines, it is found that the pi
      interaction of CPD and 1-octene is stronger than that of DCPD.

PMID- 18630957
TI  - Effect of molecular architecture on phase behavior of graft copolymers.
AB  - Influence of molecular architecture on phase behavior of graft copolymer melts
      was studied by using a reciprocal-space self-consistent filed theory (SCFT). The
      phase diagrams were examined as functions of the architectural parameters
      describing the graft copolymers (i.e., the number of grafts and the position of
      first junction). In comparison with the well-known phase diagram of diblock
      copolymers, the phase diagrams of the graft copolymers are asymmetric. When the
      number of grafts or the position of first junction varies, the boundaries of
      order-order transitions have shifts due to the variation in the chain stretching
      energy. The change in molecular architecture also significantly alters the domain
      spacing of ordered structures but has weak impact on the density distributions of
      graft copolymers. For comparison of the theoretical predictions with the existing
      experimental results, the phase diagrams of graft copolymers were also calculated
      at strong segregation. The SCFT calculations can accurately capture the
      characteristics of the phase behavior of graft copolymer melts.

PMID- 18630958
TI  - Alkylammonium-based protic ionic liquids. II. Ionic transport and heat-transfer
      properties: fragility and ionicity rule.
AB  - The physicochemical characterization of six alkylammonium-based protic ionic
      liquids (PILs) is presented. These compounds were prepared through a simple and
      atom-economic neutralization reaction between a tertiary amine and a Bronsted
      acid, HX, where X- is HCOO-, CH3COO-, HF2-. The temperature dependency and the
      effect of added water on properties such as density, viscosity, ionic
      conductivity, and the thermal comportment of these PILs were measured and
      investigated. The results allowed us to classify them according to a classical
      Walden diagram and to appreciate their great "fragility". PILs have applicable
      perspectives in replacements of conventional inorganic acids for fuel cell
      devices and thermal transfer fluids.

PMID- 18630959
TI  - Gas-phase mechanisms of degradation of hazardous organophosphorus compounds: do
      they follow a common pattern of alkaline hydrolysis reaction as in
      phosphotriesterase?
AB  - A comprehensive ab initio analysis of the gas-phase mechanisms of alkaline
      hydrolysis for a number of phosphotriesterase substrates--O,O-diisopropyl
      phosphorofluoridate (DFP), O-isopropyl methyl phosphonofluoridate, O,O-diethyl p
      nitrophenyl phosphate (paraoxon), O,O-diethyl p-nitrophenyl thiophosphate
      (parathion), N-acetyl phosphoramidothioate (acephate), O,O-diethyl S-2
      ethylthioethyl phosphorothioate (demeton-S) and O-ethyl N,N-dimethyl
      phosphoramidocyanidate--has been presented herein. The results indicate that,
      although an associative mechanism of alkaline hydrolysis is followed by all these
      compounds, P-F and P-CN bonds are cleaved according to the multistep addition
      elimination scheme, whereas the breakage of P-O and P-S bonds appears to be
      consistent with the one-step direct-displacement mechanism. Of the two
      alternative reaction pathways present in all those cases (except of acephate),
      the most probable one involves the proton from a nucleophilic hydroxide
      experiencing an additional stabilization by the phosphoryl oxygen atom.

PMID- 18630960
TI  - Improving the properties of chitosan as support for the covalent multipoint
      immobilization of chymotrypsin.
AB  - Changing gel structure and immobilization conditions led to a significant
      improvement in the covalent multipoint attachment of chymotrypsin on chitosan.
      The use of sodium alginate, gelatin, or kappa-carrageenan, activation with
      glutaraldehyde, glycidol, or epichlorohydrin, and addition of microorganisms
      followed by cellular lysis allowed the modification of the gel structure.
      Immobilization yields, recovered activities, and stabilization factors at 55 and
      65 degrees C were evaluated. Enzyme immobilization for 72 h at pH 10.05, 25
      degrees C and reduction with NaBH 4 in chitosan 2.5%-carrageenan 2.5%, with
      addition of S. cerevisiae 5% and activation with epichlorohydrin led to the best
      derivative, which was 9900-fold more stable than the soluble enzyme. This support
      allowed an enzyme load up to 40 mg chymotrypsin x g gel (-1). The number of
      covalent bonds, formed by active groups in the support and lysine residues of the
      enzyme, can explain the obtained results. SEM images of the gel structures
      corroborate these conclusions.

PMID- 18630961
TI  - PLGA microsphere construct coated with TGF-beta 3 loaded nanoparticles for
      neocartilage formation.
AB  - Polymeric microsphere system has been widely used in tissue-regeneration matrix
      and drug delivery systems. To apply these biomaterials as novel cell supporting
      matrix for stem cell delivery, we have devised a novel method for the fabrication
      of nanostructured 3D scaffolds that growth factor loaded heparin/poly(L-lysine)
      nanoparticles were physically attached on the positively charged surface of PLGA
      microspheres precoated with low molecular weight of poly(ethyleneimmine) (PEI)
      via a layer-by-layer (LbL) system. Based on a previous study, we have prepared
      poly(lactide-co-glycolide) (PLGA) microspheres harboring heparin/poly(L-lysine)
      loaded with growth factors. Growth factor loaded heparin/poly(L-lysine)
      nanoparticles, which were simply produced as polyion complex micelles (PICM) with
      diameters of 50-150 nm, were fabricated in the first step. Microsphere matrix
      (size, 20 approximately 80 nm) containing TGF-beta 3 showed a significantly
      higher number of specific lacunae phenotypes at the end of the 4 week study in
      vitro culture of mesenchymal stem cells. Thus, growth factor delivery of PLGA
      microsphere can be used to engineer synthetic extracellular matrix. This PLGA
      microsphere matrix containing TGF-beta 3 showed promise as coatings for
      implantable biomedical devices to improve biocompatibility and ensure in vivo
      performance.

PMID- 18630963
TI  - Structural effects on the solvolytic reactivity of carboxylic and sulfonic acid
      chlorides. Comparisons with gas-phase data for cation formation.
AB  - Kinetic data for solvolyses of 28 acid chlorides in 97% w/w trifluoroethanol
      (TFE)-water spanning over 10 (9) in rate constant at 25 degrees C are obtained
      directly or by short extrapolation from published values. G3 calculations of the
      energy required for cation formation in the gas phase are validated from proton
      affinities and from other experimental data. G3 calculations of heterolytic bond
      dissociation enthalpies (HBDEs) for formation of cations from acid chlorides in
      the gas phase show the following trends when compared with the solvolysis rate
      constants: (i) electron-rich sulfonyl chlorides and most carboxylic acid
      chlorides, including thione derivatives, give a satisfactory linear correlation
      with a significant negative slope; (ii) most sulfonyl chlorides and some
      chloroformates and thio derivatives have higher HBDEs and fit another correlation
      with a small, negative slope. A significant deviation is observed for the acyl
      series (RCOCl), for which both solvolysis rates and HBDEs increase in the order R
      = Bu ( t ) < Pr ( i ) < Et < Me. The deviation may be explained either by a prior
      hydration mechanism or preferably by electrostatic effects on the formation of
      small cations. The above results of structural effects support independent
      evidence from solvent effects that cationic ionization reaction pathways (with
      nucleophilic solvent assistance or S N2 character) are involved in the solvolyses
      of acid chlorides.

PMID- 18630962
TI  - Sinulodurins A and B, antiproliferative and anti-invasive diterpenes from the
      soft coral Sinularia dura.
AB  - Two new diterpenes, sinulodurin A (1) and sinulodurin B (2), along with two known
      sterols, 24 S-methyl cholesterol and 24-methylene cholesterol, were isolated from
      the Palau soft coral Sinularia dura. The structures of the new metabolites were
      determined on the basis of spectroscopic methods and by comparison of NMR data
      with those of related metabolites. Sinulodurin A (1) and sinulodurin B (2) showed
      antiproliferative activity against highly malignant +SA mammary epithelial cells
      with an IC 50 range of 20-30 microM. They also displayed anti-invasive activity
      against human highly metastatic prostate cancer PC-3M-CT+ cells in the spheroid
      disaggregation assay. Furthermore, the antimicrobial activities of the isolates
      were tested.

PMID- 18630964
TI  - Neighboring group participation by sulfonamido nitrogen.
AB  - The ability of sulfonamido nitrogen to enter into neighboring group participation
      was established in two different reaction settings. The first was uncovered
      during the bromination of benzodiazocine 8 in dichloromethane at 0 degrees C, and
      the second during the base treatment of 15a en route to allene 18.

PMID- 18630965
TI  - Stereochemical preferences in 4-center syn-eliminations from gaseous ions.
AB  - Concerted unimolecular eliminations from ionized sec-alkyl aryl ethers (ROAr
      (+*)) display a preference for producing double bonds with trans geometry. This
      preference can be assessed quantitatively, provided that a regioselective variant
      can be found. Expulsion of neutral alkenes via syn-elimination to give ionized
      ArOH does not exhibit a pronounced preference with regard to the direction of
      elimination. By contrast, ionized 2-hexyl p-trifluoromethylphenyl ether
      eliminates neutral ArOH regioselectively, giving ionized 2-hexenes rather than
      ionized 1-hexene. Vicinally monodeuterated 2-hexyl and 3-hexyl ethers were
      prepared as pure diastereomers. Metastable ion decompositions of their gaseous
      radical cations are compared over two different time windows. The
      regioselectivity for the 2-hexyl ether allows the geometric preference for the
      double bonds to be estimated based on the difference between the erythro and
      threo monodeuterated diastereomers ( trans/ cis = 2.0 for producing ionized 2
      hexene from parent ions with the lowest internal energies). The 3-hexyl ethers
      and ionized 2- and 3-phenoxyoctanes also undergo stereoselective elimination but
      give experimental values that reflect their lack of regioselectivity. Examination
      of erythro/ threo combinations shows that GC/MS/MS has the ability to quantitate
      stereochemistry in mixtures containing both positional and stereoisomers.

PMID- 18630966
TI  - Synthesis of fullerooxazoles: novel reactions of [60]fullerene with nitriles
      promoted by ferric perchlorate.
AB  - The ferric perchlorate-mediated reactions of C 60 with various nitriles in o
      dichlorobenzene under nitrogen atmosphere afforded the rare fullerooxazoles,
      which would be difficult to prepare by other methods. A possible reaction
      mechanism for the formation of the fullerooxazoles was proposed.

PMID- 18630967
TI  - Germanium(II)-mediated reductive cross-aldol reaction of bromoaldehydes with
      aldehydes: NMR studies and ab initio calculations.
AB  - A highly practical reductive cross-aldol reaction of alpha-bromoaldehydes with
      various aldehydes has been developed using Ge(II)Cl 2 to produce aldehyde
      germanium(IV) aldolates, which were directly transformed to various
      multifunctionalized compounds. A remarkable change in stereoselectivity depended
      on the alpha-bromoaldehydes employed; secondary alpha-bromoaldehydes gave syn
      selectivities, while tertiary alpha-bromoaldehydes accomplished the synthesis of
      anti-selective aldol products with a quaternary carbon center. NMR studies and X
      ray analysis strongly suggested the formation of germanium enolate in the
      reaction of alpha-bromoaldehyde 2h with GeCl 2-dioxane. Detailed mechanistic
      studies, including NMR analysis and ab initio calculations, revealed the
      generation of stable germanium aldolates, which was due to the remarkably low
      Lewis acidity of the germanium(IV).

PMID- 18630968
TI  - Soft metal-mediated base pairing with novel synthetic nucleosides possessing an
      O,S-donor ligand.
AB  - Metal-mediated base pairing with artificial ligand-bearing nucleosides allows
      site-selective metal incorporation inside DNA duplexes. In particular, this
      strategy has provided a general way of discrete, heterogeneous metal arrays in a
      programmable manner. To increase the kind of metallo-building blocks, we have
      newly synthesized two artificial nucleosides which have an O, S-donor ligand as
      the nucleobase moiety, mercaptopyridone ( M) and hydroxypyridinethione ( S).
      These nucleosides were found to efficiently form metal-mediated base pairs with
      soft transition metal ions such as Pd (2+) and Pt (2+).

PMID- 18630970
TI  - One-pot parallel solution-phase synthesis of 1-substituted 4-(2-aminoethyl)-1H
      pyrazol-5-ols.
AB  - Two variations of enaminone-based parallel solution-phase synthesis of 1
      substituted 4-(2-aminoethyl)-1 H-pyrazol-5-ols 8 and their NH-tautomers 8' were
      developed. The synthetic strategy comprises a two step preparation of the N
      protected alpha-enamino lactams 3a and 3b from 2-pyrrolidinone (1), "ring
      switching" transformation of 3a, b with monosubstituted hydrazines 4a-u, and
      acidolytic removal of the N-protecting group. In order to ensure a clean and fast
      conversion, reactions of Cbz-enaminone 3a with hydrazines 4a-k were carried out
      under microwave irradiation to afford the "ring-switched" intermediates 7a-k.
      Deprotection of 7a-k with HBr-AcOH at 50 degrees C gave a library of 11
      analytically pure 4-(2-aminoethyl)-1 H-pyrazol-5-ols (di)hydrobromides 8/ 8'a-k
      in 16-75% yields over two steps. The other reagent, Boc-enaminone 3b, was more
      reactive and ring switching transformations with hydrazines 4b, d, k proceeded
      smoothly and cleanly under conventional heating. Finally, a parallel one-pot
      transformation of the Boc-enaminone 3b with hydrazines 4a-u followed by
      subsequent deprotection of the intermediates 9a-u with HCl-EtOAc furnished a
      library of 21 analytically pure 4-(2-aminoethyl)-1 H-pyrazol-5-ols
      (di)hydrochlorides 8/ 8'a-u in 40-100% yields.

PMID- 18630971
TI  - Silver-mediated synthesis of heterocycles.

PMID- 18630972
TI  - Impermeable atomic membranes from graphene sheets.
AB  - We demonstrate that a monolayer graphene membrane is impermeable to standard
      gases including helium. By applying a pressure difference across the membrane, we
      measure both the elastic constants and the mass of a single layer of graphene.
      This pressurized graphene membrane is the world's thinnest balloon and provides a
      unique separation barrier between 2 distinct regions that is only one atom thick.

PMID- 18630973
TI  - A hybrid plasmonic-photonic nanodevice for label-free detection of a few
      molecules.
AB  - Noble metal nanowaveguides supporting plasmon polariton modes are able to
      localize the optical fields at nanometer level for high sensitivity biochemical
      sensing devices. Here we report on the design and fabrication of a novel photonic
      plasmonic device which demonstrates label-free detection capabilities on single
      inorganic nanoparticles and on monolayers of organic compounds. In any case, we
      determine the Raman scattering signal enhancement and the device detection limits
      that reach a number of molecules between 10 and 250. The device can be
      straightforwardly integrated in a scanning probe apparatus with the possibility
      to match topographic and label-free spectroscopic information in a wide range of
      geometries.

PMID- 18630974
TI  - Multiple reaction monitoring of mTRAQ-labeled peptides enables absolute
      quantification of endogenous levels of a potential cancer marker in cancerous and
      normal endometrial tissues.
AB  - While iTRAQ analyses have proved invaluable for the discovery of potential cancer
      markers, two outstanding issues that remained were its ineffectiveness to
      consistently detect specific proteins of interest in a complex sample and to
      determine the absolute abundance of those proteins. These have been addressed by
      availability of the mTRAQ reagents (Applied Biosystems, Inc., Foster City, CA) a
      nonisobaric variant of iTRAQ. We have applied this newly emerging technique to
      quantify one of our potential markers for endometrial cancer, viz. pyruvate
      kinase M1/M2. The mTRAQ methodolgy relies on multiple reaction monitoring (MRM)
      to target tryptic peptides from the protein of interest, thus, ensuring maximal
      opportunity for detection, while the nonisobaric tags enable specific
      quantification of each version of the labeled peptides through unique MRM
      transitions conferred by the labels. Known amounts of synthetic peptides tagged
      with one of the two available mTRAQ labels, when used as quantification standards
      in a mixture with the oppositely labeled tryptically digested sample, permit
      determination of the absolute amounts of the corresponding protein in the sample.
      The ability to label the sample and reference peptides with either one of the two
      possible combinations is an inherent advantage of this method, as it provides a
      means for verification of the reported ratios. In this study, we determined that
      the amount of pyruvate kinase present in the homogenate from a biopsied EmCa
      tissue sample was 85 nmol/g of total proteins, while the equivalent concentration
      in the nonmalignant controls was 21-26 nmol/g of total proteins. This
      approximately 4-fold higher amount of pyruvate kinase in the cancer sample was
      further confirmed not only by a direct comparison between the cancer sample and
      one of the nonmalignant controls, but also independently by an enzyme-linked
      immunosorbant assay (ELISA). Additionally, the 4-fold higher level of pyruvate
      kinase amount in the cancer homogenate reported in this study is considerably
      higher than the 2-fold higher ratio reported across 20 cancer samples in the
      discovery phase with the iTRAQ technique, suggesting that there exists a
      possibility that the dynamic range of ratios determined by the iTRAQ technique
      may have been compressed.

PMID- 18630975
TI  - Monitoring of Saccharomyces cerevisiae cell proliferation on thiol-modified
      planar gold microelectrodes using impedance spectroscopy.
AB  - An impedance spectroscopic study of the interaction between thiol-modified Au
      electrodes and Saccharomyces cerevisiae of strain EBY44 revealed that the cells
      formed an integral part of the interface, modulating the capacitive properties
      until a complete monolayer was obtained, whereas the charge transfer resistance (
      R ct) to the redox process of [Fe(CN)6] 3-/4- showed a linear relationship to the
      number of cells even beyond the monolayer coverage. R ct showed strong pH
      dependence upon increasing the pH of the utilized buffer to 7.2. Upon addition of
      S. cerevisiae cells at pH 7.2, the obtained value of R ct showed over 560%
      increase with respect to the value obtained on the same thiol-modified electrode
      without cells. It was demonstrated that real-time monitoring of S. cerevisiae
      proliferation, with frequency-normalized imaginary admittance (real capacitance)
      as the indicator, was possible using a miniaturized culture system, ECIS
      Cultureware, with integrated planar cysteamine-modified Au microelectrodes. A
      monolayer coverage was reached after 20-28 h of cultivation, observed as an
      approximately 15% decrease in the real capacitance of the system.

PMID- 18630977
TI  - Effect of open metal sites on adsorption of polar and nonpolar molecules in metal
      organic framework Cu-BTC.
AB  - Atomistic grand canonical Monte Carlo simulations were performed in this work to
      investigate the role of open copper sites of Cu-BTC in affecting the separation
      of carbon monoxide from binary mixtures containing methane, nitrogen, or
      hydrogen. Mixtures containing 5%, 50%, or 95% CO were examined. The simulations
      show that electrostatic interactions between the CO dipole and the partial
      charges on the metal-organic framework (MOF) atoms dominate the adsorption
      mechanism. The binary simulations show that Cu-BTC is quite selective for CO over
      hydrogen and nitrogen for all three mixture compositions at 298 K. The removal of
      CO from a 5% mixture with methane is slightly enhanced by the electrostatic
      interactions of CO with the copper sites. However, the pore space of Cu-BTC is
      large enough to accommodate both molecules at their pure-component loadings, and
      in general, Cu-BTC exhibits no significant selectivity for CO over methane for
      the equimolar and 95% mixtures. On the basis of the pure-component and low
      concentration behavior of CO, the results indicate that MOFs with open metal
      sites have the potential for enhancing adsorption separations of molecules of
      differing polarities, but the pore size relative to the sorbate size will also
      play a significant role.

PMID- 18630976
TI  - Quantifying nanoparticle adhesion mediated by specific molecular interactions.
AB  - Receptor-mediated targeting of nanometric contrast agents or drug carriers holds
      great potential for treating cardiovascular and vascular-associated diseases.
      However, predicting the ability of these vectors to adhere to diseased cells
      under dynamic conditions is complex due to the interplay of transport,
      hydrodynamic force, and multivalent bond formation dynamics. Therefore, we sought
      to determine the effects of adhesion molecule density and flow rate on adhesion
      of 210 nm particles, with the goal of identifying criteria to optimize binding
      efficiency and selectivity. Our system employed a physiologically relevant
      ligand, the vascular adhesion molecule ICAM-1, and an ICAM-1 specific antibody
      tethered to the nanoparticle using avidin-biotin chemistry. We measured binding
      and dissociation of these particles in a flow chamber as a function of antibody
      density, ligand density, and flow rate, and using a transport-reaction model we
      distilled overall kinetic rate constants for adhesion and detachment from the
      binding data. We demonstrate that both attachment and detachment of 210 nm
      particles can be correlated with receptor and ligand valency and are minimally
      affected by shear rate. Furthermore, we uncovered a time-dependent mechanism
      governing particle detachment, in which the rate of detachment decreases with
      contact time according to a power law. Finally, we use our results to illustrate
      how to engineer adhesion selectivity for specific molecular targeting
      applications. These results establish basic principles dictating nanoparticle
      adhesion and dissociation and can be used as a framework for the rational design
      of targeted nanoparticle therapeutics that possess optimum adhesive
      characteristics.

PMID- 18630978
TI  - Zeta potentials and Debye screening lengths of aqueous, viscoelastic surfactant
      solutions (cetyltrimethylammonium bromide/sodium salicylate system).
AB  - In a series of experiments, we studied the dynamic properties of aqueous
      surfactant solutions of cetyltrimethylammonium bromide (CTAB) at conditions after
      adding different amounts of sodium salicylate (NaSal). The aggregates, present in
      these solutions, are elongated, wormlike micelles, which tend to form
      entanglement networks. The viscoelastic, gel-like samples were analyzed by means
      of static, dynamic, and electrophoretic light scattering techniques. We
      separately investigated the effects of surfactant concentration and added salt on
      intermicellar interactions. The electrostatic interactions between the
      anisometric micelles were analyzed by considering the effective dimensions of the
      aggregates. We calculated the Debye-Huckel lengths from experimental data of the
      osmotic second virial coefficient and from the diffusion second virial
      coefficient. It turned out that the results were in good agreement with
      theoretically estimated values. We also measured the zeta potential and intensity
      of scattered light in a large range of different salt concentrations keeping the
      CTAB concentration constant. We observed an isoelectric point and charge reversal
      of the threadlike micelles at an excess salicylate concentration of about 100 mM.
      The observed decrease of the zeta potential points to striking processes of
      counterion condensation. In these solutions, the salicylate ion acts as a
      cosurfactant, due to its discrepancy between polar and hydrophobic groups. We
      also detected a simple linear correlation between the zeta potentials and the
      Debye screening lengths of the surfactant solutions.

PMID- 18630979
TI  - Properties of poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl-polyglycidol)
      microspheres suspended in water. Effect of sodium chloride and temperature on
      particle diameters and electrophoretic mobility.
AB  - Hydrodynamic and electrophoretic properties of core-shell poly(styrene/alpha-
      tert-butoxy-omega-vinylbenzyl-polyglycidol) (P(S/PGL)) microspheres suspended in
      water are described. The microspheres were obtained by surfactant-free emulsion
      copolymerization of styrene and alpha- tert-butoxy-omega-vinylbenzyl-polyglycidol
      macromonomer ( M n = 2800, M w/ M n = 1.05). The process yielded microspheres
      with number average diameter D n = 270 nm and with low diameter dispersity index
      D w/ D n = 1.01. Shells of P(S/PGL) microspheres were enriched in polyglycidol.
      Molar fraction of polyglycidol monomeric units in the shells (determined by X-ray
      photoelectron spectroscopy) was equal to 0.34, which is much higher than the
      average molar fraction of polyglycidol monomeric units in whole particles of
      0.048. Influences of NaCl concentration and temperature on P(S/PGL) microsphere
      diameters and on their electrophoretic mobility were investigated. It was found
      that hydrodynamic diameter of P(S/PGL) microspheres, determined by photon
      correlation spectroscopy, decreased significantly when temperature did exceed a
      certain value (transition temperature, T t). It has been found that the decrease
      is more pronounced for higher concentrations of NaCl in the medium. For
      microspheres suspended in 10 (-1) M NaCl, the hydrodynamic diameter decreased by
      8% whereas for the same particles in pure water the diameter decreased by 5.2%.
      The process of shrinkage was fully reversible. Values of T t for P(S/PGL)
      microspheres were lower for higher concentrations of NaCl. Adjustment of salt
      concentration allowed controlling T t in a range from 44.4 to 49.9 degrees C. 13C
      NMR relaxation time measurements (T 1) for carbon atoms in polyglycidol
      macromonomer revealed that T 1 did increase with increasing temperature (in
      temperature range from 25 to 75 degrees C) indicating higher motion of chains at
      higher temperature. Addition of NaCl did not induce a substantial change of T 1
      in the mentioned temperature range. The swelling-deswelling properties of
      P(S/PGL) microspheres' interfacial layer affected adsorption of P(S/PGL)
      particles on modified with (3-aminopropyl)triethoxysilane mica. It was shown that
      the deposition of P(S/PGL) microspheres at 25 degrees C on mica led to formation
      of two-dimensional crystal-shape assemblies, whereas at 60 degrees C (far above T
      t = 49.8 degrees C in H2O) the microspheres were randomly adsorbed without
      formation of colloidal crystal assemblies.

PMID- 18630980
TI  - Protein diffusion across the interface in aqueous two-phase systems.
AB  - We present a detailed study of the diffusive transport of proteins across a fluid
      phase boundary within aqueous two-phase systems. The aim of the work is to
      investigate whether local effects at the phase boundary cause a retardation of
      the diffusive transport between the phases. Possible modifications of interfacial
      mass transfer could be due to protein adsorption at the phase boundary or local
      electric fields from electric double layers. Experiments with a microfluidic
      system have been performed in which protein diffusion (bovine serum albumin and
      ovalbumin) within a bilaminated configuration of two phases containing
      polyethylene glycol and dextran is analyzed. A one-dimensional model
      incorporating phase-specific diffusion constants and the difference in chemical
      potential between the phases has been formulated. A comparison of experimental
      and simulation data shows a good overall agreement and suggests that a potential
      local influence of the phase boundary on protein transport is insignificant for
      the systems under investigation.

PMID- 18630982
TI  - Introduction of Dale Clayton as the Henry Baldwin Ward Medalist for 2008.

PMID- 18630983
TI  - The spectrum of intermediate syndrome following acute organophosphate poisoning:
      a prospective cohort study from Sri Lanka.
AB  - BACKGROUND: Intermediate syndrome (IMS) is a major cause of death from
      respiratory failure following acute organophosphate poisoning. The objective of
      this study was to determine repetitive nerve stimulation (RNS) predictors of IMS
      that would assist in patient management and clinical research. METHODS AND
      FINDINGS: Seventy-eight consenting symptomatic patients with organophosphate
      poisoning were assessed prospectively with daily physical examination and RNS.
      RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20,
      and 30 Hz. The study was conducted as a prospective observational cohort study in
      the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients
      using a priori clinical diagnostic criteria, and five of them developed
      respiratory failure. All ten patients showed progressive RNS changes correlating
      with the severity of IMS. A decrement-increment was observed at intermediate and
      high frequencies preceding the onset of clinical signs of IMS. As the patient
      developed clinical signs of IMS, decrement-increment was progressively noted at
      low and intermediate frequencies and a combination of decrement-increment and
      repetitive fade or severe decrement was noted at high frequencies. Severe
      decrement preceded respiratory failure in four patients. Thirty patients
      developed forme fruste IMS with less severe weakness not progressing to
      respiratory failure whose RNS was characterized by decrement-increment or a
      combination of decrement-increment and repetitive fade but never severe
      decrements. CONCLUSIONS: Characteristic changes in RNS, preceding the development
      of IMS, help to identify a subgroup of patients at high risk of developing
      respiratory failure. The forme fruste IMS with the characteristic early changes
      on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and
      precede the diagnosis and complications of IMS. Thus they may be useful in
      clinical management and research.

PMID- 18630984
TI  - Diabetes mellitus increases the risk of active tuberculosis: a systematic review
      of 13 observational studies.
AB  - BACKGROUND: Several studies have suggested that diabetes mellitus (DM) increases
      the risk of active tuberculosis (TB). The rising prevalence of DM in TB-endemic
      areas may adversely affect TB control. We conducted a systematic review and a
      meta-analysis of observational studies assessing the association of DM and TB in
      order to summarize the existing evidence and to assess methodological quality of
      the studies. METHODS AND FINDINGS: We searched the PubMed and EMBASE databases to
      identify observational studies that had reported an age-adjusted quantitative
      estimate of the association between DM and active TB disease. The search yielded
      13 observational studies (n = 1,786,212 participants) with 17,698 TB cases.
      Random effects meta-analysis of cohort studies showed that DM was associated with
      an increased risk of TB (relative risk = 3.11, 95% CI 2.27-4.26). Case-control
      studies were heterogeneous and odds ratios ranged from 1.16 to 7.83. Subgroup
      analyses showed that effect estimates were higher in non-North American studies.
      CONCLUSION: DM was associated with an increased risk of TB regardless of study
      design and population. People with DM may be important targets for interventions
      such as active case finding and treatment of latent TB and efforts to diagnose,
      detect, and treat DM may have a beneficial impact on TB control.

PMID- 18630985
TI  - Organophosphate poisoning-induced intermediate syndrome: can electrophysiological
      changes help predict outcome?

PMID- 18630986
TI  - Next stop, don't block the doors: opening up access to clinical trials results.

PMID- 18630987
TI  - Persistent leatherback turtle migrations present opportunities for conservation.
AB  - Effective transboundary conservation of highly migratory marine animals requires
      international management cooperation as well as clear scientific information
      about habitat use by these species. Populations of leatherback turtles
      (Dermochelys coriacea) in the eastern Pacific have declined by >90% during the
      past two decades, primarily due to unsustainable egg harvest and fisheries
      bycatch mortality. While research and conservation efforts on nesting beaches are
      ongoing, relatively little is known about this population of leatherbacks'
      oceanic habitat use and migration pathways. We present the largest multi-year
      (2004-2005, 2005-2006, and 2007) satellite tracking dataset (12,095 cumulative
      satellite tracking days) collected for leatherback turtles. Forty-six females
      were electronically tagged during three field seasons at Playa Grande, Costa
      Rica, the largest extant nesting colony in the eastern Pacific. After completing
      nesting, the turtles headed southward, traversing the dynamic equatorial currents
      with rapid, directed movements. In contrast to the highly varied dispersal
      patterns seen in many other sea turtle populations, leatherbacks from Playa
      Grande traveled within a persistent migration corridor from Costa Rica, past the
      equator, and into the South Pacific Gyre, a vast, low-energy, low-productivity
      region. We describe the predictable effects of ocean currents on a leatherback
      migration corridor and characterize long-distance movements by the turtles in the
      eastern South Pacific. These data from high seas habitats will also elucidate
      potential areas for mitigating fisheries bycatch interactions. These findings
      directly inform existing multinational conservation frameworks and provide
      immediate regions in the migration corridor where conservation can be
      implemented. We identify high seas locations for focusing future conservation
      efforts within the leatherback dispersal zone in the South Pacific Gyre.

PMID- 18630989
TI  - Controlling size in multicellular organs: focus on the leaf.

PMID- 18630988
TI  - Humans lack iGb3 due to the absence of functional iGb3-synthase: implications for
      NKT cell development and transplantation.
AB  - The glycosphingolipid isoglobotrihexosylceramide, or isogloboside 3 (iGb3), is
      believed to be critical for natural killer T (NKT) cell development and self
      recognition in mice and humans. Furthermore, iGb3 may represent an important
      obstacle in xenotransplantation, in which this lipid represents the only other
      form of the major xenoepitope Galalpha(1,3)Gal. The role of iGb3 in NKT cell
      development is controversial, particularly with one study that suggested that NKT
      cell development is normal in mice that were rendered deficient for the enzyme
      iGb3 synthase (iGb3S). We demonstrate that spliced iGb3S mRNA was not detected
      after extensive analysis of human tissues, and furthermore, the iGb3S gene
      contains several mutations that render this product nonfunctional. We directly
      tested the potential functional activity of human iGb3S by expressing chimeric
      molecules containing the catalytic domain of human iGb3S. These hybrid molecules
      were unable to synthesize iGb3, due to at least one amino acid substitution. We
      also demonstrate that purified normal human anti-Gal immunoglobulin G can bind
      iGb3 lipid and mediate complement lysis of transfected human cells expressing
      iGb3. Collectively, our data suggest that iGb3S is not expressed in humans, and
      even if it were expressed, this enzyme would be inactive. Consequently, iGb3 is
      unlikely to represent a primary natural ligand for NKT cells in humans.
      Furthermore, the absence of iGb3 in humans implies that it is another source of
      foreign Galalpha(1,3)Gal xenoantigen, with obvious significance in the field of
      xenotransplantation.

PMID- 18630990
TI  - Considering the first steps toward a stable and orderly way of bacterial life.

PMID- 18630991
TI  - Improved tropical forest management for carbon retention.

PMID- 18630992
TI  - Using field data and weight of evidence to develop water quality criteria.
AB  - In the United States, ambient aquatic life water quality criteria are derived
      using guidelines developed in 1985 that include a clear and consistent
      methodology using data from standard toxicity tests. The methodology from these
      guidelines has been successful, but a broader methodology is needed because some
      effects of pollutants do not lend themselves to conventional toxicity testing.
      Criterion assessment is proposed as that methodology. In criterion assessment, a
      specific environmental goal is translated into a measurable benchmark of effect
      that is used together with a modeled exposure-response relationship to estimate a
      range of exposures that will achieve the specific goal. The model of the exposure
      response relationships and the benchmark effect are developed from field data and
      laboratory data using multiple analytical methods. Then the model is solved for
      the effect, thereby estimating the criterion, an upper threshold for acceptable
      exposures. The resulting candidate criteria are synthesized to select criteria
      and other benchmark values, such as remedial goals. The criterion assessment
      process is illustrated using the US Environmental Protection Agency Framework for
      Developing for Suspended and Bedded Sediments Water Quality Criteria, which
      recommends developing alternative candidate criterion values and then evaluating
      them to select a final criterion. Candidate criteria may be derived from models
      of field observations, field manipulations, laboratory tests, or empirical and
      theoretical models. Final selection of a criterion uses a weight-of-evidence
      comparison that engenders confidence because causal associations are confirmed on
      the basis of different assumptions, independent data sets, and varied statistical
      methods, thereby compensating for the concerns raised by individual studies and
      methods. Thus, it becomes possible to specify criteria for agents with biological
      or physical modes of action, as well as those with chemical modes of action, to
      best achieve environmental goals.

PMID- 18630993
TI  - Rare tumor of the tongue in a child: alveolar soft part sarcoma.
AB  - Alveolar soft part sarcoma (ASPS) is a rare, malignant tumor of uncertain
      histogenesis that has no benign counterpart. In some cases, a structural
      rearrangement of chromosome 17 involving band q25 has been reported. The neoplasm
      occurs most frequently in female adolescents and young adults, where it arises
      predominantly in the extremities. In contrast, the most common sites of
      occurrence in infants and children are the orbit (41%) and the tongue (25%). The
      primary therapeutic option is a complete surgical excision. Because of the
      indolent growth and lack of pain associated with the mass, 20% of patients have
      metastases at the time of initial diagnosis. Median survival time reported for
      all sites of the body is 79 months. When ASPS presents in the tongue region,
      however, the patients involved are usually children and have a better prognosis
      than patients affected in the extremities. The utility of adjuvant chemotherapy
      or radiation therapy in children is open to question. Because metastases may
      occur after several decades, children with ASPS should be followed throughout
      adolescence and well into adulthood. Only 10 cases of ASPS occurring in the
      tongues of children younger than 5 years of age were indexed by MEDLINE between
      1952 and 2006. Here, we describe the 1st case consistent with typical ASPS of the
      tongue in 15 years at our hospital. The patient is a 2-year-old girl who has been
      disease-free for 32 months.

PMID- 18630994
TI  - Thyroid societies across the world.

PMID- 18630995
TI  - Expanding indications for recombinant human TSH in thyroid cancer.

PMID- 18630996
TI  - Whither TSH receptor blocking antibodies in the treatment of Graves' disease?

PMID- 18630997
TI  - Rosiglitazone effect on radioiodine uptake in thyroid carcinoma patients with
      high thyroglobulin but negative total body scan: a correlation with the
      expression of peroxisome proliferator-activated receptor-gamma.
AB  - BACKGROUND: Thyroid carcinoma patients with high thyroglobulin (Tg) level but
      negative total body scan (TBS) are difficult to treat with radioiodine (RAI). The
      objective of this study was to determine if treatment with rosiglitazone (RZ), a
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, was
      associated with an increase in RAI uptake in thyroid carcinoma patients with high
      serum Tg and negative TBSs. We also determined if there was a correspondence
      between the effect of RZ and the degree of staining for PPAR-gamma within thyroid
      cancer tissues. METHODS: We prescribed 8 mg of RZ daily for 6 weeks in 23
      patients with epithelial cell thyroid carcinoma who previously had negative
      posttherapeutic I-131 total body scans (post Rx TBSs) with high serum Tg
      concentrations. Diagnostic total body scans (Dx TBSs) before and 6 weeks after RZ
      treatment were compared. An ablative dose of I-131 was then given to all
      patients, and post Rx TBS was performed to evaluate RAI uptake.
      Immunohistochemical staining of PPAR-gamma expression in thyroid cancer biopsies
      was done to correlate this with possible effects of RZ on RAI uptake. RESULTS:
      Seven patients had strong PPAR-gamma-positive staining in thyroid biopsies, nine
      patients had weakly positive staining, and seven patients had negative staining.
      Five of seven patients with strong staining had either positive post Rx TBS, or
      both Dx TBS and post Rx TBS. One of nine patients with weak staining had positive
      Dx TBS and post Rx TBS. In contrast, none of the seven patients with negative
      staining had positive TBS. CONCLUSIONS: RZ can increase RAI uptake in thyroid
      tissue in the majority of patients with epithelial cell thyroid carcinoma whose
      previous posttherapeutic I-131 scans were negative provided they have high
      intensity and extent of PPAR-gamma expression in thyroid tissue. Few, if any,
      patients with weak or no PPAR-gamma expression in thyroid cancer tissue increase
      RAI uptake after RZ treatment.

PMID- 18630998
TI  - Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid
      disease.
AB  - BACKGROUND: Since the histological expression of galectins is increased in
      thyroid carcinoma, determination of their serum levels may provide useful
      preoperative information. The goal of this study was to determine if a difference
      in galectin serum levels could be detected between benign and malignant nodular
      thyroid diseases. DESIGN: Using validated ELISAs, the concentrations of several
      galectins were prospectively measured in serum samples from 30 healthy
      individuals and preoperatively in 90 patients with thyroid disease. Seventy-one
      patients had multiple thyroid nodules (MTN), 13 patients had a single thyroid
      nodule (STN), and 6 patients had Graves' disease. Nine of 71 patients with MTN
      had fine-needle aspiration biopsy (FNAB) of their nodules and in 7 patients a
      "benign" diagnosis was made, in 0 patient a "malignant" diagnosis was made, and
      in 2 patients a "suspicious" diagnosis was made. Six of 13 patients with STN had
      FNAB of their nodules and in 2 patients a "benign" diagnosis was made, in 3
      patients a "malignant" diagnosis was made, and in 1 patient a "suspicious"
      diagnosis was made. RESULTS: Thyroid disease was associated with higher levels of
      galectins-1 and -3 compared to normal subjects. Using a threshold value of 3.2
      ng/mL as a cut-off point, the measurement of serum galectin-3 separated micro-
      and macropapillary thyroid carcinoma (PAP_CA) from patients with nonmalignant
      thyroid disease with 74% specificity, 73% sensitivity, 57% positive predictive
      value, and 85% negative predictive value. Elevated serum galectin-3
      concentrations (>3.2 ng/mL) detected 87% of macropapillary thyroid carcinomas and
      67% of micropapillary thyroid carcinomas. CONCLUSIONS: Serum levels of galectins
      1 and -3 are relatively high in patients with thyroid malignancy but there is
      considerable overlap in serum galectin-3 concentrations between those with benign
      and malignant nodular thyroid disease and, to a lesser extent, between those with
      and without nodular thyroid disease.

PMID- 18630999
TI  - 18F-FDG PET in the management of patients with anaplastic thyroid carcinoma.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive
      solid tumors in humans. The use of positron emission tomography (PET) with 18F
      fluorodeoxyglucose (18F-FDG) in ATC has not been studied, and only a few case
      reports have been published. The objective of this study was to investigate the
      potential contribution of 18F-FDG PET to the clinical management of patients with
      ATC. METHODS: All patients with ATC studied with 18F-FDG PET from August 2001
      through March 2007 were included. The PET results were correlated with computed
      tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and
      clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake
      value. Any change in the treatment plan as a direct result of the PET findings as
      documented in the clinical notes was recorded. RESULTS: Sixteen patients were
      included. True-positive PET findings were seen for all primary tumors, in all
      nine patients with lymph node metastases, in five out of eight patients with lung
      metastases, and in two patients with distant metastases other than lung
      metastases. In 8 of the 16 patients, the medical records reported a direct impact
      of the PET findings on the clinical management. CONCLUSIONS: ATC demonstrates
      intense uptake on 18F-FDG PET images. In 8 of the 16 patients (50%), the medical
      records reported a direct impact of the PET findings on the management of the
      patient. PET may improve disease detection and have an impact on the management
      of patients with ATC relative to other imaging modalities.

PMID- 18631000
TI  - Comparison between minimally invasive video-assisted thyroidectomy and
      conventional thyroidectomy: is there any evidence-based information?
AB  - BACKGROUND: The aim of this study was to test the hypothesis that minimally
      invasive video-assisted thyroidectomy (MIVAT) affords comparable safety and
      efficacy as to the open conventional surgery in dealing with patients with small
      thyroid nodules. METHODS: Randomized controlled trials comparing the MIVAT with
      open thyroidectomy were ascertained by methodical search using Medline, Embase,
      Pubmed, and The Cochrane Library. Primary meta-analysis outcomes were adverse
      events (laryngeal nerve palsy and hypoparathyroidism), and cosmesis and secondary
      outcomes were operative time, blood loss, and early and late postoperative pain.
      RESULTS: Operative time was significantly less with open thyroidectomy than with
      MIVAT, while MIVAT was associated with less pain at 6 hours postoperatively.
      Blood loss did not reached significance between procedures. Comparisons between
      two procedures concerning pain score of 24 and 48 hours, respectively, depicted
      statistically significant differences in favor of the MIVAT but only in the fixed
      effects model. MIVAT was associated with less scarring. There were no
      statistically significant differences for the presence of transient recurrent
      laryngeal nerve palsy and the presence of transient hypoparathyroidism.
      CONCLUSIONS: MIVAT is a safe procedure that produces outcomes; in view of short
      term adverse events, similar to those of open thyroidectomy, it needs a longer
      operative time to be accomplished and is superior in terms of immediate
      postoperative pain and cosmetic results.

PMID- 18631001
TI  - Thyroidectomy for Hashimoto's thyroiditis: complications and associated cancers.
AB  - BACKGROUND: Hashimoto's thyroiditis is usually treated medically; however,
      thyroidectomy is sometimes indicated. Thyroiditis can make thyroid dissection
      more difficult and possibly increase the risk of surgical complications. The aim
      of this study was to determine the rate of complications and associated cancer in
      patients with Hashimoto's thyroiditis. METHODS: Retrospective series of 474
      patients treated surgically at the University of California, San Francisco,
      between January 1985 and June 2005 with final pathology demonstrating Hashimoto's
      thyroiditis, chronic lymphocytic thyroiditis, or chronic thyroiditis. Parameters
      evaluated included demographics, surgical indications, and postoperative
      complications. RESULTS: Among the 474 patients, 133 had thyroidectomy because of
      preoperative diagnosis of thyroid cancers (median age 39 years; 116 females and
      17 males), 316 had thyroidectomy because of benign thyroid nodules or goiter
      (median age 47.5 years; 292 females and 24 males), and 25 had thyroidectomy to
      relieve local symptoms caused by thyroiditis but did not have thyroid nodules
      (median age 42 years; 25 females). No death or permanent surgical complications
      occurred. One hundred and fifty-two patients (32.1%) had transient postoperative
      hypocalcemia, 2 (0.4%) had transient recurrent nerve palsy, and 4 (0.8%) had a
      postoperative neck hematoma. Fifty-three percent had thyroid cancer at final
      histological examination. CONCLUSIONS: Thyroidectomy can be performed in patients
      with Hashimoto's thyroiditis with a low risk of permanent surgical complications.
      Cancer is common in patients who have a thyroidectomy for Hashimoto's thyroiditis
      even when not suspected preoperatively.

PMID- 18631002
TI  - A human monoclonal autoantibody to the thyrotropin receptor with thyroid
      stimulating blocking activity.
AB  - BACKGROUND: Human monoclonal autoantibodies (MAbs) are valuable tools to study
      autoimmune responses. To date only one human MAb to the thyrotropin (TSH)
      receptor (TSHR) with stimulating activity has been available. We now describe the
      detailed characterization of a blocking type human MAb to the TSHR. METHODS: A
      single heterohybridoma cell line was isolated from the peripheral blood
      lymphocytes of a patient with severe hypothyroidism (TSH 278 mU/L) using standard
      techniques. The line stably expresses a TSHR autoantibody (5C9; IgG1/kappa).
      Ability of 5C9 to bind and compete with 125I-TSH or TSHR antibodies binding to
      the TSHR was tested using tubes coated with solubilized TSHR. Furthermore, the
      blocking effects of 5C9 on stimulation of cyclic AMP production was assessed
      using Chinese hamster ovary (CHO) cells expressing the wild-type human TSHR or
      TSHRs with amino acid mutations. MAIN OUTCOME: 5C9 IgG bound to the TSHR with
      high affinity (4 x 10(10) L/mol) and inhibited binding of TSH and a thyroid
      stimulating human monoclonal autoantibody (M22) to the receptor. 5C9 IgG
      preparations inhibited the cyclic AMP-stimulating activities of TSH, M22, serum
      TSHR autoantibodies and thyroid-stimulating mouse monoclonal antibodies.
      Furthermore 5C9 reduced the constitutive activity of wild-type TSHR and TSHR with
      some activating mutations. The effect of different amino acid mutations in the
      TSHR on 5C9 biological activity was studied and TSHR Lys129Ala or Asp203Ala
      completely abolished the ability of 5C9 to block TSH-mediated stimulation of
      cyclic AMP production. CONCLUSIONS: The availability of 5C9 provides new
      opportunities to investigate the binding and biological activity of TSHR blocking
      type autoantibodies including studies at the molecular level. Furthermore,
      monoclonal antibodies such as 5C9 may well provide the basis of new drugs to
      control TSHR activity including applications in thyroid cancer and Graves'
      ophthalmopathy.

PMID- 18631003
TI  - Thyroid autoimmunity in schoolchildren in an area with long-standing iodine
      sufficiency: correlation with gender, pubertal stage, and maternal thyroid
      autoimmunity.
AB  - BACKGROUND: A strong genetic background and gender are believed to be involved in
      thyroid autoimmunity (TA). The age these factors become manifest is less clear,
      however. The objective of the present study was to determine the prevalence of TA
      in children and adolescents and to determine if there are relationships between
      the period of onset of TA and gender and between TA and maternal autoimmunity.
      METHODS: Antithyroperoxidase antibodies (anti-TPO Ab), antithyroglobulin
      antibodies (anti-Tg Ab), thyrotropin, thyroxine, triiodothyronine, and urinary
      iodine were determined in 440 healthy schoolchildren (200 boys and 240 girls),
      aged 5-18 years, and in 123 mothers living in an iodine-replete region. RESULTS:
      The prevalence of positive anti-TPO and anti-Tg Ab was 4.6% and 4.3%,
      respectively. In girls, the prevalence of positive anti-TPO Ab was higher in
      Tanner stage II-V compared to Tanner stage I (8.2% vs. 2.2%; p < 0.05). No
      difference was detected with regard to anti-Tg Ab. In girls, positive anti-TPO
      and anti-Tg Ab levels were associated with significantly greater thyroid volume.
      Hypoechogenicity was detected in 52.6% and 36.8% of the children with positive
      anti-TPO or anti-Tg Ab, respectively (p = 0.0005). The prevalence of autoimmune
      thyroiditis, as defined by positive serum anti-TPO and/or anti-Tg and an
      echographic pattern of the thyroid gland having diffuse or irregular
      hypoechogenicity, was 2.5%. Mothers of anti-TPO Ab positive children had positive
      anti-TPO Ab more frequently compared to mothers of anti-TPO Ab negative children
      (82% vs. 18%; p = 0.0005). Mothers of anti-Tg Ab positive children had positive
      anti-Tg Ab more frequently compared to mothers of anti-Tg Ab negative children
      (75% vs. 25%; p = 0.0005). CONCLUSIONS: These findings demonstrate that thyroid
      antibody positivity in children was significantly associated with maternal
      autoimmunity and their development in girls emerges at puberty. Since heredity,
      female gender, and puberty are strongly associated with TA, girls in families
      with TA should be examined at the onset of puberty.

PMID- 18631004
TI  - Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic
      autoimmune thyroiditis (Hashimoto's thyroiditis) treated with levothyroxine.
AB  - BACKGROUND: A number of studies show that the serum levels of antithyroid
      peroxidase antibodies (TPO-Ab) in patients with Hashimoto's thyroiditis decline
      during levothyroxine treatment, but do not provide quantitative data or report
      the fraction of patients in whom test for TPO-Ab became negative ("normalization
      percentage"). The objective of the present study was to provide this information.
      METHODS: This was a retrospective study of TPO-Ab concentrations in 36 women and
      2 men (mean age 51 +/- 16 years; range 19-81 years) with Hashimoto's thyroiditis
      as defined by the following criteria: elevated plasma TPO-Ab and typical
      hypoechogenicity of the thyroid in high-resolution sonography at first
      presentation or during follow-up and low pertechnetate uptake in thyroid
      scintigraphy. When first studied 17 women and 1 man were not yet taking
      levothyroxine. The remaining 20 patients were receiving levothyroxine. At initial
      examination 18 patients had serum thyroid-stimulating hormone (TSH)
      concentrations above normal. Results of up to eight (mean = 5.8) measurements
      obtained over a mean period of 50 months while patients were receiving
      levothyroxine were analyzed. In addition, serum TSH, free triiodothyronine (fT3),
      and free thyroxine (fT4) were measured, and ultrasound of the neck was performed
      at each follow-up examination. RESULTS: In terms of TPO-Ab levels, 35 of 38
      patients (92%) had a decrease, 2 patients had undulating levels, and 1 patient
      had an inverse hyperbolic increase in her TPO-Ab levels. In the 35 patients in
      whom there were decreasing TPO-Ab values, the mean of the first value was 4779
      IU/mL with an SD of 4099 IU/mL. The mean decrease after 3 months was 8%, and
      after 1 year it was 45%. Five years after the first value, TPO-Ab levels were
      1456 +/- 1219 IU/mL, a decrease of 70%. TPO-Ab levels became negative, < 100
      IU/mL, in only six patients, a normalization percentage of 16%. There were no
      correlations between changes in thyroid volume and changes in TPO-Ab. CONCLUSION:
      Serum TPO-Ab levels decline in most patients with Hashimoto's thyroiditis who are
      taking levothyroxine, but after a mean of 50 months, TPO-Ab became negative in
      only a minority of patients.

PMID- 18631005
TI  - Differential regulation of the myosin heavy chain genes alpha and beta in rat
      atria and ventricles: role of antisense RNA.
AB  - BACKGROUND: The myosin heavy chain (MHC) genes are regulated by triiodothyronine
      (T3) in a reciprocal and chamber-specific manner. To further our understanding of
      the potential mechanisms involved, we determined the T3 responsiveness of the MHC
      genes, alpha and beta, and the beta-MHC antisense (AS) gene in the rat ventricles
      and atria. METHODS: Hypothyroid rats were administered a single physiologic (1
      microg) or pharmacologic (20 microg) dose of T3, and sequential measurements of
      beta-MHC hn- and AS RNA and alpha-MHC heterogeneous nuclear RNA from rat
      ventricular and atrial myocardium were performed with reverse transcription PCR.
      RESULTS: We have demonstrated that T3 treatment increases the myocyte content of
      an AS beta-MHC RNA in atria and ventricles that includes sequences complementary
      to both the first 5' and last 3' introns of the beta-MHC sense transcript. In the
      hypothyroid rat ventricle, beta-MHC sense RNA expression is maximal, while in the
      euthyroid rat ventricle, beta-MHC AS RNA is maximal. beta-MHC AS expression
      increased by 52 +/- 9.8% at the peak, 24 hours after injection of a physiologic
      dose of T3 (1 microg/animal), while beta-MHC sense RNA decreased by 41 +/- 2.2%
      at 36 hours, the nadir. In hypothyroid atria, beta-MHC AS RNA was induced by
      threefold within 6 hours of administration of 1 microg T3, demonstrating that in
      the atria, beta-MHC AS expression is regulated by T3, while alpha-MHC expression
      is not. CONCLUSIONS: In the hypothyroid rat heart ventricle, beta-MHC AS RNA
      expression increases in response to T3 similar to that of alpha-MHC. Simultaneous
      measures of beta-MHC sense RNA are decreased, suggesting a possible mechanism for
      AS to regulate sense expression. In atria, while alpha-MHC is not influenced by
      thyroid state, beta-MHC sense and AS RNA were simultaneously and inversely
      altered in response to T3. This confirms a close positive relationship between T3
      and beta-MHC AS RNA in both the atria and ventricles, while demonstrating for the
      first time that alpha- and beta-MHC expression is not coupled in the atria.

PMID- 18631006
TI  - Factors influencing the study of peroxidase-generated iodine species and
      implications for thyroglobulin synthesis.
AB  - A key issue in the mechanism of thyroglobulin (Tg) iodination by thyroperoxidase
      (TPO) is whether a TPO-bound iodine intermediate directly iodinates Tg
      incorporated tyrosines (specific iodination) or whether reactive iodine species
      released from TPO effectuate Tg iodination (nonspecific iodination). We addressed
      these alternatives by (a) determining the aqueous equilibria of the iodine
      species potentially involved in the kinetic studies of TPO-mediated iodination,
      and (b) reviewing the structure of the substrate channel in mammalian
      peroxidases. Redox-potentiometric analysis of aqueous iodine combined with
      integrated mathematical modelling demonstrates that I2 reacts with water to form
      several iodine species including hypoiodious acid (HOI). The HOI/I2 ratio depends
      on time, iodide concentration, buffering agents, and pH varying dramatically from
      pH 4 to 7.4. These factors may confound the use of Michaelis-Menten kinetics to
      determine the mechanism of TPO-catalyzed iodination since both I2 and HOI
      iodinate tyrosine but with different specificities and reaction rates.
      Consequently there is as yet no conclusive kinetic evidence that iodination
      occurs via formation of a TPO-bound iodinated intermediate. Furthermore,
      knowledge of TPO structure, gained from X-ray crystallographic studies indicates
      that access of Tg-bound tyrosyl groups to the active site of TPO is not possible.
      Thus the emerging conclusion is that the mechanism of Tg iodination is
      nonspecific. This is consistent with the occurrence of thyroid hormone formation
      in prevertebrate ascidians which exhibit TPO-like activity but lack the Tg gene.

PMID- 18631007
TI  - A new germline point mutation in Ret exon 8 (cys515ser) in a family with
      medullary thyroid carcinoma.
AB  - BACKGROUND: A novel Cys-Ser Ret germline point mutation in a 58-year-old woman
      with bilateral medullary thyroid carcinoma (MTC) prompted us to perform genetic
      analysis of the family and evaluate the biological consequences of such a
      mutation. METHODS: Ret analysis by direct sequencing was performed in five family
      members. The biological activity and biochemical properties of the Ret- Cys515Ser
      mutant were analyzed in NIH-3T3 cells. RESULTS: The proband's son, age 35, had
      the Ret- Cys515Ser mutation and the L769 CTT/CTG exon 13 polymorphic variant,
      which was also found in his father. Clinical evaluation of the son also revealed
      bilateral multifocal microscopic MTC and papillary thyroid carcinoma (PTC). In
      vitro and in vivo analysis indicated ligand-independent activation of the Ret
      Cys515Ser mutant due to aberrant disulfide homodimerization, increased mitogenic
      activity, and ability to induce anchorage-independent growth in NIH-3T3 cells in
      comparison to wild-type Ret, suggesting a possible role of Cys515Ser in tumor
      development. CONCLUSIONS: The Cys515Ser mutation adds to cysteine substitution
      groups that have been described in association with MTC. Our data also highlight
      the importance of performing a complete genetic analysis in patients who present
      with MTC.

PMID- 18631008
TI  - Phenotypic variation among four family members with congenital hypothyroidism
      caused by two distinct thyroglobulin gene mutations.
AB  - BACKGROUND: Thyroglobulin (Tg) is a large glycoprotein that is intimately
      involved in the biosynthesis of thyroxine and triiodothyronine. At least 38
      mutations have been described in the Tg gene that are associated with varying
      degrees of hypothyroidism. We studied the Tg gene in four related subjects with
      congenital hypothyroidism. SUMMARY: We found a novel compound heterozygous
      constellation (IVS30 + 1G>T/A2215D) in a brother and sister and one previously
      described related mutation (IVS30+1G>T) in their two sibling second degree
      cousins. The brother with the IVS30 + 1G>T/A2215D mutation and the two siblings
      with the IVS30+1G>T mutation had fetal or neonatal goiter and all had
      hypothyroidism. CONCLUSIONS: This study further confirms the association of the
      IVS30+G>T mutation of the Tg gene with hypothyroidism. Computer analysis predicts
      that the A2215D mutation, first reported here, should cause structural
      instability of Tg but when present as a compound heterozygous mutation with
      IVS30+G>T/A its effect is unclear but is likely to be influenced by iodine
      intake.

PMID- 18631009
TI  - Symptomatic hyponatremia in association with a low-iodine diet and levothyroxine
      withdrawal prior to I131 in patients with metastatic thyroid carcinoma.
AB  - BACKGROUND: Strategies to improve I131 uptake in thyroid carcinoma include
      levothyroxine (LT4) withdrawal or thyrotropin (TSH) administration along with a
      low-iodine diet. We report five patients with papillary or follicular thyroid
      carcinoma who developed symptomatic hyponatremia during LT4 withdrawal and low
      iodine diet. RESULTS: Four patients had pulmonary and/or brain metastases. All
      had restricted iodine intakes during LT4 withdrawal. Presenting complaints
      included weakness, dizziness, fainting spells, lethargy, and/or nausea. Baseline
      serum sodium levels while on LT4 suppression were normal. During presentation all
      were hypothyroid and serum sodium ranged from 110 to 121 mmol/L (normal 135-148).
      Despite hyponatremia, the plasma renin activity and serum aldosterone levels were
      suppressed, indicating volume expansion. The hyponatremia responded to fluid
      restriction and normalized after LT4 replacement. Low sodium intake,
      inappropriate antidiuretic hormone secretion syndrome (SIADH)-like disorder
      secondary to hypothyroidism and/or lung or cerebral metastases may have
      contributed to hyponatremia. CONCLUSIONS: The development of hyponatremia during
      LT4 withdrawal and low-iodine diet in otherwise healthy patients with thyroid
      carcinoma is extremely rare. However, elderly patients with metastatic thyroid
      carcinoma need observation during LT4 withdrawal combined with a low-iodine diet
      and should receive instruction to take iodine-free sodium chloride. Free water
      restriction may be necessary in some patients.

PMID- 18631010
TI  - A "semihot-semicold" but "pure" adenoma.

PMID- 18631011
TI  - Drug-induced thyroiditis and papillary carcinoma in a minocycline-pigmented black
      thyroid gland.
AB  - We describe a 31-year-old woman who had ingested minocycline for 18 months prior
      to presenting with hyperthyroidism and a palpable thyroid nodule. There was no
      evidence of Graves' disease or autonomous nodule on thyroid scintigraphy, and a
      clinical diagnosis of thyroiditis was made. Fine-needle aspiration biopsy of the
      palpable lesion suggested papillary carcinoma, and the patient underwent a total
      thyroidectomy. Intraoperatively, the thyroid gland was found to have a striking
      black discoloration. Subsequent histological examination revealed the
      accumulation of pigment globules within the apical cytoplasm of the follicular
      cells, and associated findings of a drug-induced thyroiditis. The tumor nodule
      showed features of infarction and was felt to represent a necrotic papillary
      microcarcinoma. We postulate that in addition to causing black thyroid
      pigmentation, chronic minocycline use in our patient resulted in thyroiditis and
      subsequent hyperthyroidism. The papillary microcarcinoma was probably a
      coincidental finding.

PMID- 18631012
TI  - Thyroid invasion by locally advanced esophageal cancer masquerading as anaplastic
      carcinoma.

PMID- 18631013
TI  - Impact of the ovarian hyperstimulation syndrome on thyroid function.

PMID- 18631014
TI  - Percutaneous laser ablation of an autonomous thyroid nodule: effects on nodule
      size and histopathology of the nodule 2 years after the procedure.

PMID- 18631015
TI  - Urinary perchlorate excretion does not predict thyroid function among pregnant
      women.

PMID- 18631016
TI  - Sunitinib-associated lymphocytic thyroiditis without circulating antithyroid
      antibodies.

PMID- 18631017
TI  - Correspondence between ultrasonography and histological features in a single
      thyroid nodule with coexisting follicular adenoma and papillary carcinoma.

PMID- 18631018
TI  - Serial changes in liver function tests in patients with subacute thyroiditis.

PMID- 18631020
TI  - Compound poisson approximation of the number of occurrences of a position
      frequency matrix (PFM) on both strands.
AB  - Transcription factors play a key role in gene regulation by interacting with
      specific binding sites or motifs. Therefore, enrichment of binding motifs is
      important for genome annotation and efficient computation of the statistical
      significance, the p-value, of the enrichment of motifs is crucial. We propose an
      efficient approximation to compute the significance. Due to the incorporation of
      both strands of the DNA molecules and explicit modeling of dependencies between
      overlapping hits, we achieve accurate results for any DNA motif based on its
      Position Frequency Matrix (PFM) representation. The accuracy of the p-value
      approximation is shown by comparison with the simulated count distribution.
      Furthermore, we compare the approach with a binomial approximation, (compound)
      Poisson approximation, and a normal approximation. In general, our approach
      outperforms these approximations or is equally good but significantly faster. An
      implementation of our approach is available at http://mosta.molgen.mpg.de.

PMID- 18631021
TI  - Using atom mapping rules for an improved detection of relevant routes in weighted
      metabolic networks.
AB  - Computational analysis of pathways in metabolic networks has numerous
      applications in systems biology. While graph theory-based approaches have been
      presented that find biotransformation routes from one metabolite to another in
      these networks, most of these approaches suffer from finding too many routes,
      most of which are biologically infeasible or meaningless. We present a novel
      approach for finding relevant routes based on atom mapping rules (describing
      which educt atoms are mapped onto which product atoms in a chemical reaction).
      This leads to a reformulation of the problem as a lightest path search in a
      degree-weighted metabolic network. The key component of the approach is a new
      method of computing optimal atom mapping rules.

PMID- 18631022
TI  - An exact algorithm for the geodesic distance between phylogenetic trees.
AB  - The geometrical representation of the space of phylogenetic trees implies a
      metric on the space of weighted trees. This metric, the geodesic distance, is the
      length of the shortest path through that space. We present an exact algorithm to
      compute this metric. For biologically reasonable trees, the implementation allows
      fast computations of the geodesic distance, although the running time of the
      algorithm is worst-case exponential. The algorithm was applied to pairs of 118
      gene trees of the metazoa. The results show that a special path in tree space,
      the cone path, which can be computed in linear time, is a good approximation of
      the geodesic distance. The program GeoMeTree is a python implementation of the
      geodesic distance, and it is approximations and is available from
      www.cibiv.at/software/geometree.

PMID- 18631023
TI  - Efficiently identifying max-gap clusters in pairwise genome comparison.
AB  - The spatial clustering of genes across different genomes has been used to study
      important problems in comparative genomics, from identification of operons to
      detection of homologous regions. A set of formal models and algorithms of so
      called max-gap clusters have been proposed recently. These algorithms guarantee
      the completeness of the results, and the simplicity of the model enables a
      rigorous statistical test of significance. These features overcome the weakness
      of many previous methods, which are often heuristic in nature. We developed a
      very efficient algorithm to compute max-gap clusters in pairwise genome
      comparison. Our algorithm is an order-of-magnitude faster than the previous
      algorithm based on the same model under a number of different settings. In our
      evaluation on two bacterial genomes, we showed that our method could identify
      known operons as well as some novel structures in the genome. We also
      demonstrated that the current framework for conserved spatial clustering of genes
      can be used to detect homologous regions in higher organisms, through the
      comparison of human and mouse genomes.

PMID- 18631024
TI  - Real-time gene expression: statistical challenges in design and inference.
AB  - Advances in microtechnologies are making it possible for high-throughput control
      and reporting of gene expression in live cells, in real-time. We explore relevant
      statistical challenges to modeling and inference in real-time gene expression
      data from single-shock experiments, with special attention on potential
      confounding between treatment and cell cycle variation. We propose a semi-wavelet
      non-linear dynamic regression model to infer modulation in gene expression due to
      treatment shocks in the presence of cell cycle variation. A case study is
      performed with public data. Results are compared ignoring cell cycle. Estimation
      and inference are performed by a Bayesian approach.

PMID- 18631025
TI  - Discovering high-order patterns of gene expression levels.
AB  - This paper reports the discovery of statistically significant association
      patterns of gene expression levels from microarray data. By association patterns,
      we mean certain gene expression intensity intervals having statistically
      significant associations among themselves and with the tissue classes, such as
      cancerous and normal tissues. We describe how the significance of the
      associations among gene expression levels can be evaluated using a statistical
      measure in an objective manner. If an association is found to be significant
      based on the measure, we say that it is statistically significant. Given a gene
      expression data set, we first cluster the entire gene pool comprising all the
      genes into groups by optimizing the correlation (or more precisely,
      interdependence) among the gene expression levels within gene groups. From each
      group, we select one or several genes that are most correlated with other genes
      within that group to form a smaller gene pool. This gene pool then constitutes
      the most representative genes from the original pool. Our pattern discovery
      algorithm is then used, for the first time, to discover the significant
      association patterns of gene expression levels among the genes from the small
      pool. With our method, it is more effective to discover and express the
      associations in terms of their intensity intervals. Hence, we discretize each
      gene expression levels into intervals maximizing the interdependence between the
      gene expression and the tissue classes. From this data set of gene expression
      intervals, we discover the association patterns representing statistically
      significant associations, some positively and some negatively, with different
      tissue classes. We apply our pattern discovery methodology to the colon-cancer
      microarray gene expression data set. It consists of 2000 genes and 62 samples
      taken from colon cancer or normal subjects. The statistically significant
      combinations of gene expression levels that repress or activate colon cancer are
      revealed in the colon-cancer data set. The discovered association patterns are
      ranked according to their statistical significance and displayed for
      interpretation and further analysis.

PMID- 18631026
TI  - The complexity of deriving multi-labeled trees from bipartitions.
AB  - Recently, multi-labeled trees have been used to help unravel the evolutionary
      origins of polyploid species. A multi-labeled tree is the same as a phylogenetic
      tree except that more than one leaf may be labeled by a single species, so that
      the leaf set of a multi-labeled tree can be regarded as a multiset. In contrast
      to phylogenetic trees, which can be efficiently encoded in terms of certain
      bipartitions of their leaf sets, we show that it is NP-hard to decide whether a
      collection of bipartitions of a multiset can be represented by a multi-labeled
      tree. Even so, we also show that it is possible to generalize to multi-labeled
      trees a well-known condition that characterizes when a collection of bipartitions
      encodes a phylogenetic tree. Using this generalization, we obtain a fixed
      parameter algorithm for the above decision problem in terms of a parameter
      associated to the given multiset.

PMID- 18631099
TI  - Microtubule dynamics in cell division: exploring living cells with polarized
      light microscopy.
AB  - This Perspective is an account of my early experience while I studied the dynamic
      organization and behavior of the mitotic spindle and its submicroscopic filaments
      using polarized light microscopy. The birefringence of spindle filaments in
      normally dividing plant and animal cells, and those treated by various agents,
      revealed (a) the reality of spindle fibers and fibrils in healthy living cells;
      (b) the labile, dynamic nature of the molecular filaments making up the spindle
      fibers; (c) the mode of fibrogenesis and action of orienting centers; and (d)
      force-generating properties based on the disassembly and assembly of the fibrils.
      These studies, which were carried out directly on living cells using improved
      polarizing microscopes, in fact predicted the reversible assembly properties of
      microtubules.

PMID- 18631027
TI  - Learning from others: children's construction of concepts.
AB  - Much of children's knowledge is derived not from their direct experiences with
      the environment but rather from the input of others. However, until recently, the
      focus in studies of concept development was primarily on children's knowledge,
      with relatively little attention paid to the nature of the input. The past 10
      years have seen an important shift in focus. This article reviews this approach,
      by examining the nature of the input and the nature of the learner, to shed light
      on early conceptual learning. These findings argue against the simple notion that
      conceptual development is either supplied by the environment or innately
      specified, and instead demonstrate how the two work together. The implications
      for how children reconcile competing belief systems are also discussed.

PMID- 18631102
TI  - Natural selection in relation to complexity.
AB  - Structural complexity characterizes our representations of dissipative
      structures. As a mechanistic concept, when referred to natural systems it
      generates perplexity in the face of logically sound models. Natural selection is
      a simple mechanistic concept, whose logic is well exemplified in genetic
      algorithms. While biological traits and functions do appear to have been
      subjected to selective culling, current neo-Darwinian theory is unable to account
      for the evolution of traits or functions when many of these are taken as the
      separate objects of independent fitness functions. Soft selection, acting in a
      phenotypically holistic manner, does model selection acting upon structurally
      complex systems with many traits and functions, but does not account for the
      evolution of specific traits or functions. It is further suggested that selection
      cannot be other than a weak force in the early, generative stages of complex life
      histories, and that this is a good thing, preserving their generativity. I
      conclude that natural selection theory by itself cannot account for increases in
      structural complexity.

PMID- 18631112
TI  - A general model for the scaling of offspring size and adult size.
AB  - Understanding evolutionary coordination among different life-history traits is a
      key challenge for ecology and evolution. Here we develop a general quantitative
      model predicting how offspring size should scale with adult size by combining a
      simple model for life-history evolution with a frequency-dependent survivorship
      model. The key innovation is that larger offspring are afforded three different
      advantages during ontogeny: higher survivorship per time, a shortened juvenile
      phase, and advantage during size-competitive growth. In this model, it turns out
      that size-asymmetric advantage during competition is the factor driving evolution
      toward larger offspring sizes. For simplified and limiting cases, the model is
      shown to produce the same predictions as the previously existing theory on which
      it is founded. The explicit treatment of different survival advantages has
      biologically important new effects, mainly through an interaction between total
      maternal investment in reproduction and the duration of competitive growth. This
      goes on to explain alternative allometries between log offspring size and log
      adult size, as observed in mammals (slope = 0.95) and plants (slope = 0.54).
      Further, it suggests how these differences relate quantitatively to specific
      biological processes during recruitment. In these ways, the model generalizes
      across previous theory and provides explanations for some differences between
      major taxa.

PMID- 18631113
TI  - Auxin receptors and plant development: a new signaling paradigm.
AB  - The plant hormone auxin, in particular indole-3-acetic acid (IAA), is a key
      regulator of virtually every aspect of plant growth and development. Auxin
      regulates transcription by rapidly modulating levels of Aux/IAA proteins
      throughout development. Recent studies demonstrate that auxin perception occurs
      through a novel mechanism. Auxin binds to TIR1, the F-box subunit of the
      ubiquitin ligase complex SCF(TIR1), and stabilizes the interaction between TIR1
      and Aux/IAA substrates. This interaction results in Aux/IAA ubiquitination and
      subsequent degradation. Regulation of the Aux/IAA protein family by TIR1 and TIR1
      like auxin receptors (AFBs) links auxin action to transcriptional regulation and
      provides a model by which the vast array of auxin influences on development may
      be understood. Moreover, auxin receptor function is the first example of small
      molecule regulation of an SCF ubiquitin ligase and may have important
      implications for studies of regulated protein degradation in other species,
      including animals.

PMID- 18631114
TI  - Controlled trial measuring the effect of a feedback intervention on hand hygiene
      compliance in a step-down unit.
AB  - OBJECTIVE: To evaluate hand hygiene compliance in 2 adult step-down units (SDUs).
      DESIGN: A 6-month (from March to September 2007), controlled trial comparing 2
      SDUs, one with a feedback intervention program (ie, the intervention unit) and
      one without (ie, the control unit). SETTING: Two 20-bed SDUs at a tertiary care
      private hospital. METHODS: Hand hygiene episodes were measured by electronic
      recording devices and periodic observational surveys. In the intervention unit,
      feedback was provided by the SDU nurse manager, who explained twice a week to the
      healthcare workers the goals and targets for the process measures. RESULTS: A
      total of 117,579 hand hygiene episodes were recorded in the intervention unit,
      and a total of 110,718 were recorded in the control unit (P = .63). There was no
      significant difference in the amount of chlorhexidine used in the intervention
      and control units (34.0 vs 26.7 L per 1,000 patient-days; P = .36) or the amount
      of alcohol gel used (72.5 vs 70.7 L per 1,000 patient-days; P = .93). However, in
      both units, healthcare workers used alcohol gel more frequently than
      chlorhexidine (143.2 vs 60.7 L per 1,000 patient-days; P < .001). Nosocomial
      infection rates in the intervention and control units, respectively, were as
      follows: for bloodstream infection, 3.5 and 0.79 infections per 1,000 catheter
      days (P = .18); for urinary tract infection, 15.8 and 15.7 infections per 1,000
      catheter-days (P = .99); and for tracheostomy-associated pneumonia, 10.7 and 5.1
      infections per 1,000 device-days (P = .13). There were no cases of infection with
      vancomycin-resistant enterococci and only a single case of infection with
      methicillin-resistant Staphylococcus aureus (in the control unit). CONCLUSIONS:
      The feedback intervention regarding hand hygiene had no significant effect on the
      rate of compliance. Other measures must be used to increase and sustain the rate
      of hand hygiene compliance.

PMID- 18631115
TI  - Outbreak of Shewanella algae and Shewanella putrefaciens infections caused by a
      shared measuring cup in a general surgery unit in Korea.
AB  - OBJECTIVE: To control an outbreak of Shewanella algae and S. putrefaciens
      infections by identifying the risk factors for infection and transmission.
      DESIGN: Matched case-control study. SETTING: A university-affiliated tertiary
      acute care hospital in Seoul, Republic of Korea, with approximately 1,600 beds.
      PATIENTS: From June 20, 2003, to January 16, 2004, a total of 31 case patients
      with Shewanella colonization or infection and 62 control patients were enrolled
      in the study. INTERVENTIONS: Requirement to use single-use measuring cups and
      standard precautions (including hand washing before and after patient care and
      use of gloves). RESULTS: S. algae or S. putrefaciens was isolated from blood, for
      9 (29.0%) of 31 patients who acquired one of the organisms; from bile, for 8
      (25.8%), and from ascitic fluid, for 8 (25.8%). The attack rate of this outbreak
      was 5.8% (31 patients infected or colonized, of 534 potentially exposed on ward
      A) and the pathogenicity of the two species together was 77.4% (24 patients
      infected, of 31 who acquired the pathogens). The estimated incubation period for
      Shewanella acquisition was 3-49 days. Using logistic analysis, we identified the
      following risk factors: presence of external drainage catheters in the
      hepatobiliary system (odds ratio [OR], 20; P < .001), presence of hepatobiliary
      disease (OR, 6.4; P < .001), admission to the emergency department of the
      hospital (OR, 2.9; P = .039), wound classification of "contaminated" or "dirty or
      infected" (OR, 16.5; P = .012), an American Society of Anesthesiologists score of
      3 or higher (OR, 8.0; P = .006), duration of stay in ward A (OR, 1.1; P < .001),
      and, for women, an age of 60-69 years (OR, 13.3; P = .028). A Shewanella isolate
      was recovered from the surface of a shared measuring cup, and 12 isolates of S.
      algae showed the same pulsed-field gel electrophoresis pattern. CONCLUSIONS: This
      Shewanella outbreak had a single-source origin and spread by contact transmission
      via a contaminated measuring cup. Shewanella species are emerging as potentially
      serious human pathogens in hospitals and could be included in hospital infection
      surveillance systems.

PMID- 18631116
TI  - Antibiotic exposure and room contamination among patients colonized with
      vancomycin-resistant enterococci.
AB  - OBJECTIVE: To determine whether total and antianaerobic antibiotic exposure
      increases the risk of room contamination among vancomycin-resistant enterococci
      (VRE)-colonized patients. DESIGN AND SETTING: A 14-month study in 2 intensive
      care units at an academic tertiary care hospital in Boston, Massachusetts.
      PATIENTS: All patients who acquired VRE or were VRE-colonized on admission and
      who had environmental cultures performed. METHODS: We performed weekly
      environmental cultures (2 sites per room) and considered a room to be
      contaminated if there was a VRE-positive environmental culture during the
      patient's stay. We determined risk factors for room contamination by use of the
      Cox proportional hazards model. RESULTS: Of 142 VRE-colonized patients, 35 (25%)
      had an associated VRE-positive environmental culture. Patients who contaminated
      their rooms were more likely to have diarrhea than those who did not contaminate
      their rooms (23 [66%] of 35 vs 41 [38%] of 107; P = .005) and more likely to have
      received antibiotics while VRE colonized (33 [94%] of 35 vs 86 [80%] of 107; P =
      .02). There was no significant difference in room contamination rates between
      patients exposed to antianaerobic regimens and patients exposed to
      nonantianaerobic regimens or between patients with and patients without diarrhea,
      but patients without any antibiotic exposure were unlikely to contaminate their
      rooms. Diarrhea and antibiotic use were strongly confounded; although two-thirds
      of room contamination occurred in rooms of patients with diarrhea, nearly all of
      these patients received antibiotics. In multivariable analysis, higher mean
      colonization pressure in the ICU increased the risk of room contamination
      (adjusted hazard ratio per 10% increase, 1.44 [95% confidence interval, 1.04
      2.04]), whereas no antibiotic use during VRE colonization was protective
      (adjusted hazard ratio, 0.21 [95% confidence interval, 0.05-0.89]). CONCLUSIONS:
      Room contamination with VRE was associated with increased mean colonization
      pressure in the ICU and diarrhea in the VRE-colonized patient, whereas no use of
      any antibiotics during VRE colonization was protective.

PMID- 18631117
TI  - Potential economic impact of hospital-acquired infections in uninsured patients:
      a preliminary investigation.
AB  - We studied uninsured patients admitted to Rhode Island Hospital from January 1
      through June 30, 2005, and from January 1 through June 30, 2006. The mean total
      hospital charge for an uninsured patient with a hospital-acquired infection was
      $18,487; for those without such an infection, it was $4,951 (P < .001).
      Multivariable linear regression revealed that a hospital-acquired infection
      accounted for 11.8 excess hospital days (P = .001). Length of stay was the only
      independent variable associated with total excess hospital charges.

PMID- 18631118
TI  - Tuberculosis: a balanced diet of lipids and carbohydrates.
AB  - In spite of effective antibiotics to treat TB (tuberculosis) since the early
      1960s, we enter the new millennium with TB currently the leading cause of death
      from a single infectious agent, killing more than 3 million people worldwide each
      year. Thus an understanding of drug-resistance mechanisms, the immunobiology of
      cell wall components to elucidate host-pathogen interactions and the discovery of
      new drug targets are now required for the treatment of TB. Above the plasma
      membrane is a classical chemotype IV peptidoglycan to which is attached the
      macromolecular structure, mycolyl-arabinogalactan via a unique
      diglycosylphosphoryl bridge. The present review discusses the assembly of the
      mAGP (mycolyl-arabinogalactan-peptidoglycan) complex and the site of action of
      EMB (ethambutol), bringing forward a new era in TB research and focus for new
      drugs to combat multidrug-resistant TB.

PMID- 18631119
TI  - What we have learned from ribosome structures.
AB  - The determination of the high-resolution structures of ribosomal subunits in the
      year 2000 and of the entire ribosome a few years later are revolutionizing our
      understanding of the role of the ribosome in translation. In the present article,
      I summarize the main contributions from our laboratory to this worldwide effort.
      These include the determination of the structure of the 30S ribosomal subunit and
      its complexes with antibiotics, the role of the 30S subunit in decoding, and the
      high-resolution structure of the entire 70S ribosome complexed with mRNA and
      tRNA.

PMID- 18631120
TI  - The methyl-CpG-binding protein MeCP2 and neurological disease.
AB  - The methyl-CpG-binding protein MeCP2 was discovered over 15 years ago as part of
      a search for proteins that selectively bind methylated DNA. It is a nuclear
      protein that is largely chromatin-bound and has a strong preference for binding
      to methylated DNA sequences in vivo. Evidence from model systems shows that MeCP2
      can recruit the Sin3a co-repressor complex to promoters leading to
      transcriptional repression, therefore suggesting that MeCP2 can interpret the DNA
      methylation signal to bring about gene silencing. Mutations in the human MECP2
      gene cause the autism spectrum disorder Rett Syndrome. MeCP2 is most highly
      expressed in neurons, and mice lacking this protein show symptoms that strikingly
      parallel those of Rett patients. Surprisingly, these symptoms are efficiently
      reversed by delayed activation of a 'stopped' Mecp2 gene, raising hopes that
      human Rett syndrome may also be reversible. Future studies of MeCP2 promise to
      shed light upon brain function, neurological disease and the biology of DNA
      methylation.

PMID- 18631121
TI  - Transcription factories.
AB  - There is increasing evidence that different transcription units are transcribed
      together in discrete nuclear structures known as transcription factories. Various
      new techniques enable us to detect and characterize these structures. We review
      the latest findings and discuss how they support a model for transcription and
      chromosome organization.

PMID- 18631122
TI  - Expression of human snRNA genes from beginning to end.
AB  - In addition to protein-coding genes, mammalian pol II (RNA polymerase II)
      transcribes independent genes for some non-coding RNAs, including the
      spliceosomal U1 and U2 snRNAs (small nuclear RNAs). snRNA genes differ from
      protein-coding genes in several key respects and some of the mechanisms involved
      in expression are gene-type-specific. For example, snRNA gene promoters contain
      an essential PSE (proximal sequence element) unique to these genes, the RNA
      encoding regions contain no introns, elongation of transcription is P-TEFb
      (positive transcription elongation factor b)-independent and RNA 3'-end formation
      is directed by a 3'-box rather than a cleavage and polyadenylation signal.
      However, the CTD (C-terminal domain) of pol II closely couples transcription with
      RNA 5' and 3' processing in expression of both gene types. Recently, it was shown
      that snRNA promoter-specific recognition of the 3'-box RNA processing signal
      requires a novel phosphorylation mark on the pol II CTD. This new mark plays a
      critical role in the recruitment of the snRNA gene-specific RNA-processing
      complex, Integrator. These new findings provide the first example of a
      phosphorylation mark on the CTD heptapeptide that can be read in a gene-type
      specific manner, reinforcing the notion of a CTD code. Here, we review the
      control of expression of snRNA genes from initiation to termination of
      transcription.

PMID- 18631123
TI  - Interaction of the TFIIB zinc ribbon with RNA polymerase II.
AB  - Transcription by RNA polymerase II requires the assembly of the general
      transcription factors at the promoter to form a pre-initiation complex. The
      general transcription factor TF (transcription factor) IIB plays a central role
      in the assembly of the pre-initiation complex, providing a bridge between
      promoter-bound TFIID and RNA polymerase II/TFIIF. We have characterized a series
      of TFIIB mutants in their ability to support transcription and recruit RNA
      polymerase II to the promoter. Our analyses identify several residues within the
      TFIIB zinc ribbon that are required for RNA polymerase II assembly. Using the
      structural models of TFIIB, we describe the interface between the TFIIB zinc
      ribbon region and RNA polymerase II.

PMID- 18631124
TI  - Chromatin switching and transcriptional regulation in disease.
AB  - Many human diseases are the result of inappropriate changes in gene expression
      resulting in deleterious phenotypes of specific cells. For example, loss of
      expression of tumour suppressors and/or ectopic expression of oncogenes underlie
      many cancers, a switch from an adult to a fetal gene-expression profile in
      cardiac myocytes results in cardiac hypertrophy and changes in the expression of
      many ion channel genes leads to a phenotypic switch from contractile to
      proliferative smooth muscle cells in vascular diseases such as neointimal
      hyperplasia and atherosclerosis. Understanding the molecular mechanisms
      responsible for these changes in gene expression is a major goal, in order to
      identify novel therapeutic targets.

PMID- 18631125
TI  - Regulation of the RelA (p65) transactivation domain.
AB  - The RelA (p65) NF-kappaB (nuclear factor kappaB) subunit contains an extremely
      active C-terminal transcriptional activation domain, required for its cellular
      function. In the present article, we review our knowledge of this domain, its
      modifications and its known interacting proteins. Moreover, we discuss how
      analysis of its evolutionary conservation reveals distinct subdomains and
      conserved residues that might give insights into its regulation and function.

PMID- 18631126
TI  - The DEAD box RNA helicases p68 (Ddx5) and p72 (Ddx17): novel transcriptional co
      regulators.
AB  - DEAD box [a motif named after its amino acid sequence (Asp-Glu-Ala-Asp)] RNA
      helicases are known to play key roles in all cellular processes that require
      modulation of RNA structure. However, in recent years, several of these proteins
      have been found to function in transcriptional regulation. In the present paper,
      we shall review the literature demonstrating the action of p68 and, where data
      are available, p72 as transcriptional co-regulators for a range of transcription
      factors, namely ERalpha (oestrogen receptor alpha), the tumour suppressor p53,
      the myogenic regulator MyoD and Runx2, a transcription factor essential for
      osteoblast development. We shall also discuss evidence indicating that, in some
      cases at least, p68 and p72 have distinct, non-redundant, roles.

PMID- 18631127
TI  - Switching genes on and off in haemopoiesis.
AB  - At present, the molecular mechanisms by which stem cells commit to and
      differentiate towards specific lineages are poorly characterized, and will need
      to be better understood before stem cells can be exploited fully in experimental
      and clinical settings. Transcriptional regulation, the ability to turn genes on
      and off, lies at the heart of these processes of lineage commitment and
      specification. We have focused on fully understanding how these decisions are
      made at a single mammalian gene locus, the alpha-globin genes, which become up
      regulated in a tissue- and developmental-stage specific manner during
      haemopoiesis. The studies summarized in the present article have revealed that
      complete regulation of this gene cluster involves not only activating mechanisms
      in expressing erythroid cells, but also repressing mechanisms, involving the
      Polycomb complex and histone deacetylases which are present in non-erythroid
      tissues. Taken together, these observations provide a well-characterized model of
      how gene expression is fully regulated during the transition from stem cells
      through lineage commitment and terminal differentiation.

PMID- 18631128
TI  - Structure and function of ribosomal RNA gene chromatin.
AB  - Transcription of the major ribosomal RNAs by Pol I (RNA polymerase I) is a key
      determinant of ribosome biogenesis, driving cell growth and proliferation in
      eukaryotes. Hundreds of copies of rRNA genes are present in each cell, and there
      is evidence that the cellular control of Pol I transcription involves adjustments
      to the number of rRNA genes actively engaged in transcription, as well as to the
      rate of transcription from each active gene. Chromatin structure is inextricably
      linked to rRNA gene activity, and the present review highlights recent advances
      in this area.

PMID- 18631129
TI  - Regulation of transcription by the Epstein-Barr virus nuclear antigen EBNA 2.
AB  - The EBNA 2 (Epstein-Barr nuclear antigen 2) transcription factor is essential for
      B-cell transformation by the cancer-associated EBV (Epstein-Barr virus) and for
      the continuous proliferation of infected cells. EBNA 2 activates transcription
      from the viral Cp (C promoter) during infection to generate the 120 kb transcript
      that encodes all nuclear antigens required for immortalization by EBV. EBNA 2
      contains an acidic activation domain and can interact with a number of general
      transcription factors and co-activators. It is now becoming clear, however, that
      the regulation of transcription elongation in addition to initiation by EBNA 2,
      at least in part through CDK9 (cyclin-dependent kinase 9)-dependent
      phosphorylation of the RNA polymerase C-terminal domain, is likely to play a
      crucial role in the mechanism of action of this key viral protein.

PMID- 18631130
TI  - The role of the Wilms' tumour-suppressor protein WT1 in apoptosis.
AB  - The Wilms' tumour-suppressor gene (WT1), encodes a zinc-finger transcription
      factor that is critical for the development of several organs, including the
      kidneys, gonads and spleen. Despite its identification as a tumour suppressor
      that plays a crucial role in the formation of a paediatric malignancy of the
      kidneys (Wilms' tumour), it has also emerged as an oncogenic factor influencing
      proliferation and apoptosis in a large variety of adult cancers. This review
      focuses on new insights into WT1's role in early development and its potential
      oncogenic role in adult cancer.

PMID- 18631131
TI  - Progesterone regulation of RUSH/SMARCA3/HLTF includes DNA looping.
AB  - RUSH/SMARCA3 (SWI/SNF-related matrix-associated actin-dependent regulator of
      chromatin subfamily A, member 3) is capable of sequence-selective DNA binding and
      ATP-dependent DNA unwinding. In rabbit uterine epithelial cells, RUSH-1alpha (113
      kDa) is the progesterone-dependent splice variant and RUSH-1beta (95 kDa) is the
      oestrogen-dependent splice variant. Rabbit RUSH/SMARCA3 mRNA is primarily
      regulated at the proximal promoter (-162/+90) via a PRE (progesterone-response
      element) half-site/overlapping Y-box domain (-38/-26) and two Sp (specificity
      protein) 3 sites centred at -128 and -58. We investigated hormone regulation by
      exploring binding of transcription factors to a putative RUSH/SMARCA3 site (-616/
      611) and the distal Sp3 (-131/-126) site. In response to progesterone, RUSH
      1alpha binds the RUSH site and the Sp3 site becomes a functional binding site for
      Egr-1 (early growth-response gene product 1)/Sp (specificity protein)1/3/MAZ (Myc
      associated zinc-finger protein)/MZF1 (myeloid zinc finger 1)/c-Rel. TransSignal
      TF-TF Interaction Arrays, supershift assays and ChIP (chromatin
      immunoprecipitation) analyses confirmed strong physical interactions between RUSH
      and Egr-1/c-Rel. Higher-order long-range interactions between RUSH and the Egr
      1/c-Rel derivative of the anisotropic flexibility of the intervening DNA sequence
      were shown with 3C (chromosome conformation capture) assays. Transient
      transfection assays with mutant constructs showed the co-operative interaction
      between RUSH and Egr-1 mediates repression by c-Rel. Thus DNA-bound RUSH/SMARCA3
      communicates with its own proximal promoter by looping the intervening DNA.
      Moreover, progesterone-dependent DNA looping is an adjunct to progesterone
      induction of the RUSH/SMARCA3 gene because the availability of RUSH isoforms and
      relevant binding partners is progesterone-regulated.

PMID- 18631132
TI  - The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP
      protein.
AB  - EBV (Epstein-Barr virus) alternates between latency and lytic replication. During
      latency, the viral genome is largely silenced by host-driven methylation of CpG
      motifs and in the switch to the lytic cycle this epigenetic silencing is
      overturned. A key event is the activation of the viral protein Zta with three
      ZREs (Zta-response elements) from the BRLF1 promoter (referred to as Rp). Two of
      these ZREs contain CpG motifs and are methylated in the latent genome.
      Biochemical analyses and molecular modelling of Zta bound to methylated RpZRE3
      indicate the precise contacts made between a serine and a cysteine residue of Zta
      with methyl cytosines. A single point mutant of Zta, C189S, is defective in
      binding to the methylated ZREs both in vitro and in vivo. This was used to probe
      the functional relevance of the interaction. ZtaC189S was not able to activate Rp
      in a B-cell line, demonstrating the relevance of the interaction with methylated
      ZREs. This demonstrates that Zta plays a role in overturning the epigenetic
      control of viral latency.

PMID- 18631133
TI  - Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein.
AB  - PTB (polypyrimidine-tract-binding protein) is a ubiquitous RNA-binding protein.
      It was originally identified as a protein with a role in splicing but it is now
      known to function in a large number of diverse cellular processes including
      polyadenylation, mRNA stability and translation initiation. Specificity of PTB
      function is achieved by a combination of changes in the cellular localization of
      this protein (its ability to shuttle from the nucleus to the cytoplasm is tightly
      controlled) and its interaction with additional proteins. These differences in
      location and trans-acting factor requirements account for the fact that PTB acts
      both as a suppressor of splicing and an activator of translation. In the latter
      case, the role of PTB in translation has been studied extensively and it appears
      that this protein is required for an alternative form of translation initiation
      that is mediated by a large RNA structural element termed an IRES (internal
      ribosome entry site) that allows the synthesis of picornaviral proteins and
      cellular proteins that function to control cell growth and cell death. In the
      present review, we discuss how PTB regulates these disparate processes.

PMID- 18631134
TI  - Subcellular localization of mRNA and factors involved in translation initiation.
AB  - Both the process and synthesis of factors required for protein synthesis (or
      translation) account for a large proportion of cellular activity. In eukaryotes,
      the most complex and highly regulated phase of protein synthesis is that of
      initiation. For instance, across eukaryotes, at least 12 factors containing 22 or
      more proteins are involved, and there are several regulated steps. Recently, the
      localization of mRNA and factors involved in translation has received increased
      attention. The present review provides a general background to the subcellular
      localization of mRNA and translation initiation factors, and focuses on the
      potential functions of localized translation initiation factors. That is, as
      genuine sites for translation initiation, as repositories for factors and mRNA,
      and as sites of regulation.

PMID- 18631135
TI  - Mechanism of ribosomal subunit joining during eukaryotic translation initiation.
AB  - Decades of research have yielded significant insight into the mechanism by which
      a cell translates an mRNA into the encoded protein. However many of the molecular
      details of the process remain a mystery. Translation initiation is an important
      control point in gene expression, and misregulation can lead to diseases such as
      cancer. A better understanding of the mechanism of translation initiation is
      imperative for the development of novel therapeutic agents. Recently, a
      combination of genetic, biochemical and biophysical studies has begun to shed
      light on how, at a molecular level, the translational machinery initiates protein
      synthesis. In the present review, we briefly compare and contrast the initiation
      pathways utilized by bacteria, archaea and eukaryotes, and then focus on
      translation initiation in eukaryotes and recent advances in our understanding of
      the subunit joining step of the process.

PMID- 18631136
TI  - Clues to the mechanism of action of eIF2B, the guanine-nucleotide-exchange factor
      for translation initiation.
AB  - A variety of cellular processes rely on G-proteins, which cycle through active
      GTP-bound and inactive GDP-bound forms. The switch between these states is
      commonly regulated by GEFs (guanine-nucleotide-exchange factors) and GAPs (GTPase
      activating proteins). Although G-proteins have structural similarity, GEFs are
      very diverse proteins. A complex example of this system is seen in eukaryotic
      translation initiation between eIF (eukaryotic initiation factor) 2, a G-protein,
      its five-subunit GEF, eIF2B, and its GAP, eIF5. eIF2 delivers Met-tRNA(i)
      (initiator methionyl-tRNA) to the 40S ribosomal subunit before mRNA binding. Upon
      AUG recognition, eIF2 hydrolyses GTP, aided by eIF5. eIF2B then re-activates eIF2
      by removing GDP, thereby promoting association of GTP. In the present article, we
      review data from studies of representative G-protein-GEF pairs and compare these
      with observations from our research on eIF2 and eIF2B to propose a model for how
      interactions between eIF2B and eIF2 promote guanine nucleotide exchange.

PMID- 18631137
TI  - Sequential waves of polyadenylation and deadenylation define a translation
      circuit that drives meiotic progression.
AB  - The maternal mRNAs that drive meiotic progression in oocytes contain short
      poly(A) tails and it is only when these tails are elongated that translation
      takes place. Cytoplasmic polyadenylation requires two elements in the 3'-UTR (3'
      untranslated region), the hexanucleotide AAUAAA and the CPE (cytoplasmic
      polyadenylation element), which also participates in the transport and
      localization, in a quiescent state, of its targets. However, not all CPE
      containing mRNAs are activated at the same time during the cell cycle, and
      polyadenylation is temporally and spatially regulated during meiosis. We have
      recently deciphered a combinatorial code that can be used to qualitatively and
      quantitatively predict the translational behaviour of CPE-containing mRNAs. This
      code defines positive and negative feedback loops that generate waves of
      polyadenylation and deadenylation, creating a circuit of mRNA-specific
      translational regulation that drives meiotic progression.

PMID- 18631138
TI  - Translational control in early development: CPEB, P-bodies and germinal granules.
AB  - Selective protein synthesis in oocytes, eggs and early embryos of many organisms
      drives several critical aspects of early development, including meiotic
      maturation and entry into mitosis, establishment of embryonic axes and cell fate
      determination. mRNA-binding proteins which (usually) recognize 3'-UTR
      (untranslated region) elements in target mRNAs influence the recruitment of the
      small ribosomal subunit to the 5' cap. Probably the best studied such protein is
      CPEB (cytoplasmic polyadenylation element-binding protein), which represses
      translation in the oocyte in a cap-dependent manner, and activates translation in
      the meiotically maturing egg, via cytoplasmic polyadenylation. Co
      immunoprecipitation and gel-filtration assays revealed that CPEB in Xenopus
      oocytes is in a very large RNP (ribonucleoprotein) complex and interacts with
      other RNA-binding proteins including Xp54 RNA helicase, Pat1, RAP55 (RNA
      associated protein 55) and FRGY2 (frog germ cell-specific Y-box protein 2), as
      well as the eIF4E (eukaryotic initiation factor 4E)-binding protein 4E-T (eIF4E
      transporter) and an ovary-specific eIF4E1b, which binds the cap weakly.
      Functional tests which implicate 4E-T and eIF4E1b in translational repression in
      oocytes led us to propose a model for the specific inhibition of translation of a
      target mRNA by a weak cap-binding protein. The components of the CPEB RNP complex
      are common to P-bodies (processing bodies), neuronal granules and germinal
      granules, suggesting that a highly conserved 'masking' complex operates in early
      development, neurons and somatic cells.

PMID- 18631139
TI  - Ribosomal acrobatics in post-transcriptional control.
AB  - High-resolution structures have given an extremely detailed view of aspects of
      ribosomes, including some near-functional states. Here, we review the importance
      of cryo-electron microscopy, among other techniques, in giving an understanding
      of the higher dynamics of the ribosome accompanying active recruitment of mRNA to
      the small subunit and translocation of tRNAs. Recent data show that careful use
      of a variety of different techniques is necessary for a proper understanding of
      the basis of function in systems such as the ribosome.

PMID- 18631140
TI  - RNA pseudoknots and the regulation of protein synthesis.
AB  - RNA pseudoknots are structural elements found in almost all classes of RNA.
      Pseudoknots form when a single-stranded region in the loop of a hairpin base
      pairs with a stretch of complementary nucleotides elsewhere in the RNA chain.
      This simple folding strategy is capable of generating a large number of stable
      three-dimensional folds that display a diverse range of highly specific functions
      in a variety of biological processes. The present review focuses on pseudoknots
      that act in the regulation of protein synthesis using cellular and viral examples
      to illustrate their versatility. Emphasis is placed on structurally well-defined
      pseudoknots that play a role in internal ribosome entry, autoregulation of
      initiation, ribosomal frameshifting during elongation and trans-translation.

PMID- 18631141
TI  - Lentiviral RNAs can use different mechanisms for translation initiation.
AB  - The full-length genomic RNA of lentiviruses can be translated to produce proteins
      and incorporated as genomic RNA in the viral particle. Interestingly, both
      functions are driven by the genomic 5'-UTR (5'-untranslated region), which
      harbours structural RNA motifs for the replication cycle of the virus. Recent
      work has shown that this RNA architecture also functions as an IRES (internal
      ribosome entry site) in HIV-1 and -2, and in SIV (simian immunodeficiency virus).
      In addition, the IRES extends to the gag coding region for all these viruses and
      this leads to the synthesis of shorter isoforms of the Gag polyprotein from
      downstream initiation codons. In the present study, we have investigated how
      different members of the lentivirus family (namely HIV-1 and -2, and SIV) can
      initiate protein synthesis by distinct mechanisms. For this, we have used the
      competitive reticulocyte lysate that we have recently described. Our results show
      that HIV-1 is able to drive the synthesis of the Gag polyprotein both by a
      classical cap-dependent mechanism and an IRES, whereas HIV-2 and SIV appear to
      use exclusively an IRES mechanism.

PMID- 18631142
TI  - Contribution of internal initiation to translation of cellular mRNAs containing
      IRESs.
AB  - A broad range of cellular stresses lead to the inhibition of translation. Despite
      this, some cellular mRNAs are selectively translated under these conditions. It
      is widely supposed that cap-independent internal initiation may maintain
      efficient translation of particular cellular mRNAs under a variety of stresses
      and other special conditions when cap-dependent protein synthesis is impaired.
      However, in spite of a large number of reports focused on the investigation of
      the regulation of IRES (internal ribosome entry site) activity in different
      tissues and under various stresses, only rarely is the real efficiency of IRES
      driven translation in comparison with cap-dependent translation evaluated. When
      precisely measured, the efficiencies of candidate IRESs in most cases appeared to
      be very low and not sufficient to compensate for the reduction of cap-dependent
      initiation under stresses. The usually low efficiency of internal initiation of
      translation is inconsistent with postulated biological roles of IRESs.

PMID- 18631143
TI  - UPF1 P-body localization.
AB  - NMD (nonsense-mediated mRNA decay) is a mechanism that degrades transcripts
      containing PTCs (premature translation termination codons). NMD is a translation
      associated process that is expected to take place throughout the cytoplasm.
      However, recent studies have indicated that the core NMD factors UPF1 (up
      frameshift-1), UPF2 and UPF3 can associate with P-bodies (processing bodies),
      which are large cytoplasmic granules replete with proteins involved in general
      mRNA decay and related processes. It has been proposed that UPF1 directs PTC
      containing mRNAs to P-bodies and triggers decay. Here, we discuss the link
      between P-bodies and NMD in view of recent studies that suggest that P-bodies are
      not required for NMD in Drosophila.

PMID- 18631144
TI  - Regulation of translation initiation by herpesviruses.
AB  - Viruses are dependent upon the host cell protein synthesis machinery, thus they
      have developed a range of strategies to manipulate host translation to favour
      viral protein synthesis. Consequently, the study of viral translation has been a
      powerful tool for illuminating many aspects of cellular translational control.
      Although much work to date has focused on translational regulation by RNA
      viruses, DNA viruses have also evolved complex mechanisms to regulate protein
      synthesis. Here we summarize work on a large family of DNA viruses, the
      Herpesviridae, which have evolved mechanisms to sustain efficient cap-dependent
      translation and to regulate the translation of specific viral mRNAs.

PMID- 18631145
TI  - Post-transcriptional regulation of gene expression by alternative 5'-untranslated
      regions in carcinogenesis.
AB  - Post-transcriptional regulation, via 5'-UTRs (5'-untranslated regions), plays an
      important role in the control of eukaryotic gene expression. Recent analyses of
      the mammalian transcriptome suggest that most of the genes express multiple
      alternative 5'-UTRs and inappropriate expression of these regions has been shown
      to contribute to the development of carcinogenesis. The present review will focus
      on the complex post-transcriptional regulation of ERbeta (oestrogen receptor
      beta) expression. In particular, results from our laboratory suggest that the
      expression of alternative 5'-UTRs plays a key role in determining the level of
      ERbeta protein expression. We have also shown that these alternative ERbeta 5'
      UTRs have a tissue-specific distribution and are differentially expressed between
      various normal and tumour tissues. Our results also suggest that alternative 5'
      UTRs can influence downstream splicing events, thereby perhaps affecting ERbeta
      function. These results suggest that alternative 5'-UTRs may have an overall
      influence on ER activity and this may have important implications for our
      understanding of cancer biology and treatment.

PMID- 18631146
TI  - Dissection of a co-translational nascent chain separation event.
AB  - Some RNA and protein sequences are capable of directing changes to the course of
      translation from that expected from the mRNA sequence, and this process is termed
      translational 'recoding'. 'CHYSEL' peptides are approximately 19-amino-acid
      sequences found in many viral genomes. When translated at internal portions of
      polypeptides, they yield co-translational separation of the nascent chain at
      their C-termini. We dissected the reaction promoted by CHYSEL sequences using
      yeast genetics and in vitro translation systems. Our results indicate that the
      reaction occurs within the peptidyltransferase centre of the ribosome where the
      nascent chain is hydrolytically released from tRNA despite the presence of
      further sense codons.

PMID- 18631147
TI  - Translational termination-re-initiation in viral systems.
AB  - Viruses have evolved a number of translational control mechanisms to regulate the
      levels of expression of viral proteins on polycistronic mRNAs, including
      programmed ribosomal frameshifting and stop codon readthrough. More recently,
      another unusual mechanism has been described, that of termination-dependent re
      initiation (also known as stop-start). Here, the AUG start codon of a 3' ORF
      (open reading frame) is proximal to the termination codon of a uORF (upstream
      ORF), and expression of the two ORFs is coupled. For example, segment 7 mRNA of
      influenza B is bicistronic, and the stop codon of the M1 ORF and the start codon
      of the BM2 ORF overlap in the pentanucleotide UAAUG (stop codon of M1 is shown in
      boldface and start codon of BM2 is underlined). This short review aims to provide
      some insights into how this translational coupling process is regulated within
      different viral systems and to highlight some of the differences in the mechanism
      of re-initiation on prokaryotic, eukaryotic and viral mRNAs.

PMID- 18631148
TI  - The emerging role of MS in structure elucidation of protein-nucleic acid
      complexes.
AB  - Developments in MS enable us to apply this technique to non-covalent complexes,
      defining their stoichiometry, subunit interactions and architectural
      organization. We illustrate the application of this non-covalent MS approach to
      uncovering the overall topological arrangements of subunits and interactions
      within RNA-protein complexes studied in our laboratory over the last 5 years.
      These studies exemplify the emerging role and potential of MS as a complementary
      structural biology methodology and demonstrate its unique niche in investigations
      of dynamic or heterogeneous protein-nucleic acid complexes, which are not
      accessible to classical high-resolution structural biology techniques.

PMID- 18631149
TI  - Single-molecule micromanipulation studies of DNA and architectural proteins.
AB  - Architectural proteins play a key role in the folding, organization and
      compaction of genomic DNA in all organisms. By bending, bridging or wrapping DNA,
      these proteins ensure that its effective volume is reduced sufficiently to fit
      inside the cell or a dedicated cellular organelle, the nucleus (in
      bacteria/archaea and in eukaryotes respectively). In addition, the properties of
      many of these proteins permit them to play specific roles as architectural
      cofactors in a large variety of DNA transactions. However, as architectural
      proteins often bind DNA with low sequence specificity and affinity, it is hard to
      investigate their interaction using biochemical ensemble techniques. Single
      molecule micromanipulation approaches that probe the properties of DNA-binding
      proteins by pulling on individual protein-DNA complexes have, in this respect,
      proved to be a very powerful alternative. Besides revealing architectural
      properties, these approaches can also reveal unique parameters not accessible to
      biochemical approaches, such as the binding kinetics and unbinding forces of
      individual proteins.

PMID- 18631150
TI  - Red light, green light: probing single molecules using alternating-laser
      excitation.
AB  - Single-molecule fluorescence methods, particularly single-molecule FRET
      (fluorescence resonance energy transfer), have provided novel insights into the
      structure, interactions and dynamics of biological systems. ALEX (alternating
      laser excitation) spectroscopy is a new method that extends single-molecule FRET
      by providing simultaneous information about structure and stoichiometry; this new
      information allows the detection of interactions in the absence of FRET and
      extends the dynamic range of distance measurements that are accessible through
      FRET. In the present article, we discuss combinations of ALEX with confocal
      microscopy for studying in-solution and in-gel molecules; we also discuss
      combining ALEX with TIRF (total internal reflection fluorescence) for studying
      surface-immobilized molecules. We also highlight applications of ALEX to the
      study of protein-nucleic acid interactions.

PMID- 18631151
TI  - Time-resolved footprinting for the study of the structural dynamics of DNA
      protein interactions.
AB  - Transcription is often regulated at the level of initiation by the presence of
      transcription factors or nucleoid proteins or by changing concentrations of
      metabolites. These can influence the kinetic properties and/or structures of the
      intermediate RNA polymerase-DNA complexes in the pathway. Time-resolved
      footprinting techniques combine the high temporal resolution of a stopped-flow
      apparatus with the specific structural information obtained by the probing agent.
      Combined with a careful quantitative analysis of the evolution of the signals,
      this approach allows for the identification and kinetic and structural
      characterization of the intermediates in the pathway of DNA sequence recognition
      by a protein, such as a transcription factor or RNA polymerase. The combination
      of different probing agents is especially powerful in revealing different aspects
      of the conformational changes taking place at the protein-DNA interface. For
      example, hydroxyl radical footprinting, owing to their small size, provides a map
      of the solvent-accessible surface of the DNA backbone at a single nucleotide
      resolution; modification of the bases using potassium permanganate can reveal the
      accessibility of the bases when the double helix is distorted or melted; cross
      linking experiments report on the formation of specific amino acid-DNA contacts,
      and DNase I footprinting results in a strong signal-to-noise ratio from DNA
      protection at the binding site and hypersensitivity at curved or kinked DNA
      sites. Recent developments in protein footprinting allow for the direct
      characterization of conformational changes of the proteins in the complex.

PMID- 18631152
TI  - Visualizing genetic loci and molecular machines in living bacteria.
AB  - An ongoing mission for biologists is to probe the molecular nature of cellular
      processes within live cells. Although much of what we have discovered during the
      molecular biology revolution of the last 50 years has been achieved by exploiting
      bacteria as 'bags of DNA and proteins', relatively little has been learnt about
      how they organize their life processes within cells. The mistaken perception of
      bacteria cells as unstructured systems arose partly because of the difficulty of
      performing studies by light microscopy due to their small size (many of them
      having cell lengths a few times bigger than the wavelength of visible light).
      With the opportunities provided by a range of new fluorophores and by new
      microscopic techniques, a revolution in bacterial cell biology is revealing
      unimagined organization in the bacterial cell. We review the development and
      exploitation of new visualization methods and reagents and show how they are
      contributing to the understanding of bacterial structure, chromosome
      organization, DNA metabolism and their relationship to the cell cycle.

PMID- 18631153
TI  - Methods for studying global patterns of DNA binding by bacterial transcription
      factors and RNA polymerase.
AB  - A major goal in the study of gene regulation is to untangle the transcription
      regulatory networks of Escherichia coli and other 'simple' organisms. To do this
      we must catalogue the binding sites of all transcription factors. ChIP (chromatin
      immunoprecipitation), combined with DNA microarray analysis, is a powerful tool
      that permits global patterns of DNA binding to be measured. Here, we discuss the
      benefits of this approach and the application of this technique to bacterial
      systems.

PMID- 18631154
TI  - Computational approaches to study transcriptional regulation.
AB  - In recent years, a number of technical and experimental advances have allowed us
      to obtain an unprecedented amount of information about living systems on a
      genomic scale. Although the complete genomes of many organisms are available due
      to the progress made in sequencing technology, the challenge to understand how
      the individual genes are regulated within the cell remains. Here, I provide an
      overview of current computational methods to investigate transcriptional
      regulation. I will first discuss how representing protein-DNA interactions as a
      network provides us with a conceptual framework to understand the organization of
      regulatory interactions in an organism. I will then describe methods to predict
      transcription factors and cis-regulatory elements using information such as
      sequence, structure and evolutionary conservation. Finally, I will discuss
      approaches to infer genome-scale transcriptional regulatory networks using
      experimentally characterized interactions from model organisms and by reverse
      engineering regulatory interactions that makes use of gene expression data and
      genomewide location data. The methods summarized here can be exploited to
      discover previously uncharacterized transcriptional pathways in organisms whose
      genome sequence is known. In addition, such a framework and approach can be
      invaluable to investigate transcriptional regulation in complex microbial
      communities such as the human gut flora or populations of emerging pathogens.
      Apart from these medical applications, the concepts and methods discussed can be
      used to understand the combinatorial logic of transcriptional regulation and can
      be exploited in biotechnological applications, such as in synthetic biology
      experiments aimed at engineering regulatory circuits for various purposes.

PMID- 18631155
TI  - The shock of the old: hydrodynamics for the masses.
AB  - Hydrodynamic techniques such as analytical ultracentrifugation can provide key
      information about subunit stoichiometry and interaction strengths of protein
      nucleic acid interactions. Analysis is complicated by (i) the need for low
      concentrations in order to observe both free and bound species and (ii)
      thermodynamic non-ideality. With the introduction of fluorescence optics, we are
      able to obtain data at lower concentrations, and improved understanding of the
      statistical thermodynamics of macromolecular solutions has allowed non-ideality
      to be accurately assigned. With these developments, it is possible now to assay
      protein-nucleic acid interactions at concentrations typically used in molecular
      biology assays.

PMID- 18631156
TI  - Higher-throughput approaches to crystallization and crystal structure
      determination.
AB  - In recent times, there has been a large increase in the number of protein
      structures deposited in the Protein Data Bank. Structural genomics initiatives
      have contributed to this expansion through their focus on high-throughput
      structural determination. This has fuelled advances in many of the techniques in
      the pipeline from gene to protein to crystal to structure. These include ligation
      independent cloning methods, parallel purification systems, robotic
      crystallization devices and automated methods of crystal identification, data
      collection and, in some cases, structure solution. Some of these advances are
      described and discussed briefly with an emphasis on activities in the York
      Structural Biology Laboratory through its participation in the Structural
      Proteomics in Europe consortium.

PMID- 18631157
TI  - Visualizing the organization and reorganization of transcription complexes for
      gene expression.
AB  - Regulated gene expression requires control of the transcription machinery,
      frequently through the establishment of different functional states of the
      transcribing enzyme RNA polymerase and its attendant activator proteins. In
      bacteria, major adaptive responses use an enhancer-dependent RNA polymerase,
      activated for transcription by a class of ATPases that remodel initial promoter
      complexes to form transcriptionally proficient open promoter complexes. In the
      present article, we summarize the integrated use of site-specific protein
      cleavage and DNA cross-linking methods, as well as FRET (fluorescence resonance
      energy transfer) in combination with X-ray crystallography and cryo-electron
      microscopy to gain insight into the organization of the enhancer-dependent sigma
      54-RNA polymerase and the ATPase-driven activation mechanism.

PMID- 18631158
TI  - WITHDRAWN:MicroRNA profile in peripheral blood T cells of patients with primary
      biliary cirrhosis.
AB  - The Ahead of Print article entitled "MicroRNA profile in peripheral blood T cells
      of patients with primary biliary cirrhosis", was withdrawn at the author's
      request.

PMID- 18631160
TI  - Correlation between colonic motility and defecatory disorders after anterior
      resection of the rectum in canine models.
AB  - The objective of this study was to describe the correlation between changes in
      colonic motility and defecatory disorders in four experimental canine models,
      with an emphasis on denervation. Therefore, we constructed a model by dividing 20
      healthy mongrel dogs into four groups, i.e. control, denervation, transection and
      anterior resection of the rectum (AR) (denervation plus transection), and focused
      on the correlation between colonic motility and defecatory disorders by counting
      the colonic migrating motor complexes (CMMCs) and colonic non-migrating motor
      complexes (CNMCs). Gastrointestinal and colonic contractile activities were
      continuously recorded on a computer with strain gauge force transducers. The
      dogs' feces were checked daily, and their consistency was recorded as normal,
      semisolid, or watery. Compared with the control group, the transection group
      showed elongation of the propagation time (P < 0.05), and the mean motility index
      of colonic contractile activity at C4 and C5 in the denervation group was greater
      than that in the control group (P < 0.05). The AR group showed three features of
      colonic motility: (i) elongation of the mean CMMC cycle (P < 0.05); (ii)
      shortening of the propagation time (P < 0.05); and (iii) increment of the number
      of CNMCs. Concerning fecal consistency, the AR group only showed watery
      diarrhoea. In conclusion, we revealed the existence of a correlation between
      defecatory disorders and changes in colonic motility. Increased knowledge among
      colorectal surgeons of the changes in colonic motility that occur following
      colorectal surgery is very important and could lead to the curtailment of
      defecatory disorders among patients.

PMID- 18631159
TI  - Two essential MYST-family proteins display distinct roles in histone H4K10
      acetylation and telomeric silencing in trypanosomes.
AB  - Chromatin modification is important for virtually all aspects of DNA metabolism
      but little is known about the consequences of such modification in
      trypanosomatids, early branching protozoa of significant medical and veterinary
      importance. MYST-family histone acetyltransferases in other species function in
      transcription regulation, DNA replication, recombination and repair. Trypanosoma
      brucei HAT3 was recently shown to acetylate histone H4K4 and we now report
      characterization of all three T. brucei MYST acetyltransferases (HAT1-3). First,
      GFP-tagged HAT1-3 all localize to the trypanosome nucleus. While HAT3 is
      dispensable, both HAT1 and HAT2 are essential for growth. Strains with HAT1 knock
      down display mitosis without nuclear DNA replication and also specific de
      repression of a telomeric reporter gene, a rare example of transcription control
      in an organism with widespread and constitutive polycistronic transcription.
      Finally, we show that HAT2 is responsible for H4K10 acetylation. By analogy to
      the situation in Saccharomyces cerevisiae, we discuss low-level redundancy of
      acetyltransferase function in T. brucei and suggest that two MYST-family
      acetyltransferases are essential due to the absence of a Gcn5 homologue. The
      results are also consistent with the idea that HAT1 contributes to establishing
      boundaries between transcriptionally active and repressed telomeric domains in T.
      brucei.

PMID- 18631161
TI  - Validity and reliability of measures of television viewing time and other non
      occupational sedentary behaviour of adults: a review.
AB  - Time spent in non-occupational sedentary behaviours (particularly television
      viewing time) is associated with excess adiposity and an increased risk of
      metabolic disorders among adults; however, there are no reviews of the validity
      and reliability of assessing these behaviours. This paper aims to document
      measures used to assess adults' time spent in leisure-time sedentary behaviours
      and to review the evidence on their reliability and validity. Medline, CINAHL and
      Psych INFO databases and reference lists from published papers were searched to
      identify studies in which leisure-time sedentary behaviours had been measured in
      adults. Sixty papers reporting measurement of at least one type of leisure-time
      sedentary behaviour were identified. Television viewing time was the most
      commonly measured sedentary behaviour. The main method of data collection was by
      questionnaire. Nine studies examined reliability and three examined validity for
      the questionnaire method of data collection. Test-retest reliabilities were
      predominantly moderate to high, but the validity studies reported large
      differences in correlations of self-completion questionnaire data with the
      various referent measures used. To strengthen future epidemiological and health
      behaviour studies, the development of reliable and valid self-report instruments
      that cover the full range of leisure-time sedentary behaviour is a priority.

PMID- 18631162
TI  - Anti-A and anti-B titers in pooled group O platelets are comparable to apheresis
      platelets.
AB  - BACKGROUND: Although uncommon, acute hemolytic transfusion reactions (AHTRs) have
      been reported after transfusion of group O single-donor apheresis platelets
      (SDPs) to group A, B, and AB recipients. Current methods for identifying "high
      titer" SDPs include tube and gel methods. The risk of a high-titer unit is
      considered low with group O, poststorage, pooled platelet concentrates (PPLTs);
      however, data regarding anti-A and anti-B titers in PPLTs are lacking. STUDY
      DESIGN AND METHODS: Anti-A and anti-B titers were determined in 185 PPLTs by
      direct agglutination using manual gel and tube methods. PPLTs tested included 124
      group O PPLTs, 25 group A PPLTs, 26 group B PPLTs, and 10 PPLTs containing a mix
      of either groups O plus A or groups O plus B (mixed PPLTs). The reciprocal of the
      highest dilution giving macroscopic agglutination was considered the agglutinin
      titer. RESULTS: Mean anti-A and anti-B titers in group O PPLTs were,
      respectively, 16 and 8 by tube and 64 and 32 by gel (p < 0.0001). Gel titers were
      one to two dilutions higher than tube and sensitive to reagent red cell lots.
      With the use of at least 64 as a critical titer, 60 percent of group O PPLTs
      tested by gel would be considered high-titer. In mixed PPLTs, the addition of one
      non-group O PLT significantly decreased or neutralized the corresponding anti-A
      or anti-B (p < 0.0001). CONCLUSION: Anti-A and anti-B titers in group O PPLTs are
      comparable to those reported in group O SDPs and significantly lower than titers
      reported in AHTR. A critical direct agglutinin titer of 64 for identifying high
      titer units by gel is too low and should be increased to 128 or higher.

PMID- 18631164
TI  - Management of blood shortages in a tertiary care academic medical center: the
      Yale-New Haven Hospital frozen blood reserve.
AB  - Threats to national and local blood supplies in America mandate development of an
      effective blood management system for emergency preparedness and efficient blood
      inventory management. Seasonal or acute blood shortages could be compounded by
      the unavoidable distribution inefficiencies of the blood pipeline during an
      emergency. The Yale-New Haven Hospital (YNHH) Blood Bank has developed a
      comprehensive emergency blood management plan, which includes maintenance of a
      tactical, limited frozen blood supply. A computer spreadsheet-based disaster
      prediction model has been designed to guide the use of the frozen reserve by
      testing various emergency scenarios. The frozen blood reserve can likely support
      normal hospital red blood cell (RBC) demands during typical (3-4 days) seasonal
      shortages, provide a reduced supply for up to 10 days, or meet an unexpected
      transient increased RBC demand without requiring intensive support from the
      regional blood center. However, the frozen blood supply is not designed to meet
      the massive transfusion demand associated with extreme or sustained disasters.
      Rather, it serves as a short-term bridge-over supply until blood center support
      can be reestablished. We review the reasons for initiating a blood management
      plan and describe how YNHH has implemented and sustains a frozen blood reserve as
      part of a comprehensive disaster management plan. Despite the operational
      complexity, the benefits of self-sufficiency, the ability to support routine
      hospital requirements, and the security of having a backup supply justify the
      expense and difficulty of maintaining a frozen blood reserve.

PMID- 18631165
TI  - Red blood cell alloantibody frequency, specificity, and properties in a
      population of male military veterans.
AB  - BACKGROUND: The prevalence of red blood cell (RBC) alloantibodies among general,
      hospital-based patients typically has averaged approximately 1 percent in various
      studies. The frequency and properties of RBC alloantibodies in military veterans
      has never been examined. STUDY DESIGN AND METHODS: Transfusion records of 18,750
      military veterans at a Department of Veterans Affairs (VA) medical center were
      retrospectively reviewed. For patients with RBC alloantibodies, the following
      were collected: sex, race/ethnicity, decade of birth, transfusion history,
      alloantibody specificity, reaction phase(s), and whether alloantibodies were
      detected at the initial type and screen or later. RESULTS: The RBC alloantibody
      prevalence was 2.4 percent among predominantly male military veterans.
      Alloantibody prevalence varied with decade of birth, ranging up to 3.3 percent
      (1911-1920). The 10 most frequent alloantibodies in males, as a percentage of
      total male antibodies, were K (21.9%), E (19.4%), D (9.1%), Le(a) (7.4%), Fy(a)
      (5.4%), c (4.8%), C (4.6%), P(1) (3.9%), Jk(a) (3.7%), and Le(b) (3.5%).
      Investigation of D alloimmunization in men revealed that antibody development
      occurred before VA care in 80 percent (39/49) of cases. For alloimmunization
      during VA care, anti-D was mostly associated with the transfusion of D+ platelets
      (7/10). The majority of alloantibodies in males reacted at the antiglobulin (AG)
      phase, even anti-Le(a), -Le(b), M, -Lu(a), and -P(1). CONCLUSION: Military
      veterans have a relatively high prevalence of RBC alloantibodies, including anti
      D, despite a large male predominance and lack of pregnancy-related
      alloimmunization. Alloantibody prevalence was highest in World War II veterans.
      The majority of male alloantibodies reacted with AG, even those traditionally
      considered to be clinically insignificant.

PMID- 18631163
TI  - Impact of nucleic acid testing for hepatitis B virus, hepatitis C virus, and
      human immunodeficiency virus on the safety of blood supply in Italy: a 6-year
      survey.
AB  - BACKGROUND: Nucleic acid testing (NAT) for hepatitis C virus (HCV) and human
      immunodeficiency virus (HIV) has been implemented in several European countries
      and in the United States, while hepatitis B virus (HBV) NAT is still being
      questioned by opinions both in favor and against such an option, depending on the
      HBV endemicity, health care resources, and expected benefits. STUDY DESIGN AND
      METHODS: This survey was aimed to assess the NAT impact in improving the safety
      of blood supply in Italy, 6 years after implementation. The study involved 93
      Italian transfusion centers and was carried out in 2001 through 2006. A total of
      10,776,288 units were tested for the presence of HCV RNA, 7,932,430 for HIV RNA,
      and 3,405,497 for HBV DNA, respectively. RESULTS: Twenty-seven donations or 2.5
      per million tested were HCV RNA-positive/anti-HCV-negative; 14 or 1.8 per million
      units tested were HIV RNA-positive/anti-HIV-negative; and 197 or 57.8 per million
      donations tested were HBV DNA-positive/hepatitis B surface antigen-negative. Of
      the latter, 8 (2.3/10(6)) were collected from donors in the window phase of
      infection and 189 (55.5/10(6)) from donors with occult HBV. Sixty-eight percent
      of the latter donors had hepatitis B surface antibody, 74.5 percent of whom with
      concentrations considered protective (>or=10 mIU/mL). CONCLUSION: NAT
      implementation has improved blood safety by reducing the risk of entering 2.5 HCV
      and 1.8 HIV infectious units per million donations into the blood supply. The
      yield of NAT in detecting infectious blood before transfusion was higher for HBV
      than for HCV or HIV. However, the benefit of HBV NAT in terms of avoided HBV
      related morbidity and mortality in blood recipients needs to be further
      evaluated.

PMID- 18631166
TI  - The effects of additive solution pH and metabolic rejuvenation on anaerobic
      storage of red cells.
AB  - BACKGROUND: Red cell (RBC) storage can be extended to 9 weeks under anaerobic or
      alkaline conditions. Simultaneous use of these approaches has not provided
      additive benefit. Our objective was to determine whether anaerobic storage with
      acidified additive solution (AS) coupled with metabolic rejuvenation might
      further improve the benefits of anaerobic storage. STUDY DESIGN AND METHODS: RBC
      storage in AS with a pH value of 6.5, 7.4, or 8.3 in aerobic or anaerobic
      conditions was examined using a panel of in vitro biochemical and RBC markers.
      RBC rejuvenation during cold storage was also evaluated. A randomized crossover
      radiolabeled recovery study (eight subjects) evaluated anaerobic RBC storage
      using AS65 with cold rejuvenation for up to 16 weeks of storage. RESULTS:
      Adenosine triphosphate (ATP) and diphosphoglycerate acid (DPG) were better
      maintained in anaerobic storage than in aerobic storage. Acidic or neutral AS
      preserved ATP concentration better, while a neutral or basic pH AS favored
      maintenance of DPG levels at higher levels for a longer period. AS pH had less of
      an effect on exposure of phosphatidylserine (PS), vesicle protein release, and
      hemolysis. Rejuvenation of RBCs during cold, anaerobic storage resulted in
      increases in ATP and DPG levels and a reversal of PS exposure. Anaerobic storage
      of RBCs in pH 6.5 AS rejuvenated at 7 weeks of storage yielded RBC 24-hour
      recoveries of 77.3 +/- 12.5 percent after 10 weeks' storage time. After a second
      rejuvenation at Week 11, six subjects' units demonstrated a recovery of 75.9 +/-
      7.3 percent at 12 weeks of storage. CONCLUSION: Extended RBC storage may be
      achieved using anaerobic conditions combined with low-pH AS and rejuvenation
      during storage.

PMID- 18631167
TI  - The American Red Cross donor hemovigilance program: complications of blood
      donation reported in 2006.
AB  - BACKGROUND: The American Red Cross (ARC) initiated a comprehensive donor
      hemovigilance program in 2003. We provide an overview of reported complications
      after whole blood (WB), apheresis platelet (PLT), or automated red cell (R2)
      donation and analyze factors contributing to the variability in reported
      complication rates in our national program. STUDY DESIGN AND METHODS:
      Complications recorded at the collection site or reported after allogeneic WB,
      apheresis PLT, and R2 donation procedures in 36 regional blood centers in 2006
      were analyzed by univariate and multivariate logistic regression. RESULTS:
      Complications after 6,014,472 WB, 449,594 PLT, and 228,183 R2 procedures totaled
      209,815, 25,966, and 12,282 (348.9, 577.5, and 538.3 per 10,000 donations),
      respectively, the vast majority of which were minor presyncopal reactions and
      small hematomas. Regional center, donor age, sex, and donation status were
      independently associated with complication rates after WB, PLT, and R2 donation.
      Seasonal variability in complications rates after WB and R2 donation correlated
      with the proportion of donors under 20 years old. Excluding large hematomas, the
      overall rate of major complications was 7.4, 5.2, and 3.3 per 10,000 collections
      for WB, PLT, and R2 procedures, respectively. Outside medical care was recorded
      at similar rates for both WB and automated collections (3.2 vs. 2.9 per 10,000
      donations, respectively). CONCLUSION: The ARC data describe the current risks of
      blood donation in a model multicenter hemovigilance system using standardized
      definitions and reporting protocols. Reported reaction rates varied by regional
      center independently of donor demographics, limiting direct comparison of
      different regional blood centers.

PMID- 18631168
TI  - Validation of HLAMatchmaker algorithm in identifying acceptable HLA mismatches
      for thrombocytopenic patients refractory to platelet transfusions.
AB  - BACKGROUND: HLAMatchmaker (HLAMM) is an algorithm that determines donor-recipient
      histocompatibility based on HLA type. This study determines the effectiveness of
      HLAMM in identifying suitable platelet (PLT) donors for refractory patients.
      STUDY DESIGN AND METHODS: Data from a previous prospectively randomized
      multicenter study comparing cross-reactive group (CREG)-matched versus serologic
      crossmatch-selected PLT transfusions in refractory patients were analyzed. By use
      of HLAMM, the compatibility of donor-recipient pairings was determined as the
      number of donor triplet mismatches (TMMs) and eplet mismatches (EMMs) and
      compared against the posttransfusion PLT corrected count increment (CCI). The
      data included 73 patients who received up to two CREG-matched and crossmatch
      selected PLT transfusions each (214 transfusions analyzed). RESULTS: TMM and EMM
      values correlated well with CREG match grade. A and BU matches had TMM and EMM
      values of 0; BX matches had TMMs and EMMs of 4 and 6 respectively; and C and D
      matches had TMMs of 10 to 21 and EMMs of 13 to 24. Fewer mismatches (TMM or EMM)
      predicted better transfusion outcomes (p < 0.05). The median 1-hour CCI was 8000
      with TMMs of not more than 9 versus 6000 with TMMs of more than 9. The median 1
      hour CCI was 7954 with EMMs of not more than 11 versus 6356 with EMMs of more
      than 11. The positive predictive value of the different methods in producing a 1
      hour CCI of more than 7500 were comparable: TMM, 56 percent; EMM, 54 percent;
      CREG, 50 percent; and crossmatching, 45 percent (p > 0.05). CONCLUSIONS: HLAMM
      (both TMM and EMM) successfully identified donors associated with good
      transfusion outcomes in refractory recipients and represents an acceptable method
      of choosing donors for refractory patients.

PMID- 18631169
TI  - Implementation of buffy coat platelet component production: comparison to
      platelet-rich plasma platelet production.
AB  - BACKGROUND: Buffy coat (BC) production of platelets (PLTs) has been successfully
      used in Europe for more than two decades. Currently, Canadian Blood Services is
      implementing the BC method. This article summarizes results of the validation
      testing performed to qualify the process of PLT production from whole blood and
      compares the quality of PLTs produced in routine production by either the PLT
      rich plasma method (PRP-PCs) or the BC method (BC-PCs). STUDY DESIGN AND METHODS:
      Validation data included variables used for routine quality control (QC; pH, PLT
      count, volume, sterility, residual white blood cell count) as well as nonroutine
      testing of PLTs for PLT activation, metabolic changes during storage, and PLT
      responsiveness to hypotonic shock and the extent of shape change induced by
      adenosine 5'-diphosphate. BC-PCs were tested on Days 1 and 6. QC of production
      runs included the same routine tests performed on Day 6. RESULTS: PLTs produced
      by the BC method during validation and pilot implementation met all Canadian
      Standards Association standards with respect to yield, volume, pH, and
      leukoreduction. Additional validation testing indicated a moderate level of PLT
      storage lesion development. In comparison to PRP-PCs, in vitro variables of BC
      PCs, either pH in this study, or other markers compared to the literature were
      better, suggesting that BC-PCs have less evidence of production-related damage
      and improved PLT quality during storage. CONCLUSIONS: PLT concentrates produced
      from whole blood by the BC method after an overnight hold have laboratory
      variables suggestive of a higher quality than those concentrates produced by the
      PRP method.

PMID- 18631170
TI  - Lung transplantation complicated by graft-versus-host disease and confounded by
      incidental transfusion-associated macrochimerism.
AB  - BACKGROUND: Passenger lymphocyte-mediated graft-versus-host disease (GVHD) in
      solid organ transplantation (SOT-GVHD) is considered a rare complication,
      particularly among recipients of lung allografts. The risk of transfusion
      associated GVHD (TA-GVHD) in solid organ transplants is also considered rare. The
      suspicion of either may be heralded by signs and symptoms of GVHD in the company
      of a population of passenger lymphocytes in excess of 1 percent (microchimerism).
      This case report illustrates the challenge of a patient who presented with
      macrochimerism both from the lung transplant allograft and from transfusions.
      STUDY DESIGN AND METHODS: Chimerism assessments of the pre- and posttransplant
      donor lung, and the recipient's aplastic marrow, were made using DNA-based
      polymerase chain reaction testing. RESULTS: Macrochimerism was observed in both
      the posttransplant aplastic host marrow and the engrafted donor lung, with the
      former predominantly consisting of lung donor lymphocytes and the latter a
      mixture of lung and presumably transfusion source donor lymphocytes. The
      pretransplant donor lung exhibited no GVHD-like pathology. CONCLUSION: This case
      demonstrates SOT-GVHD, with the unusual feature of concomitant macrochimerism
      from transfusions. SOT-GVHD likely predisposed this patient to the observed
      transfusion-associated macrochimerism. However, the dissociation between
      transfusion-attributable macrochimerism and attributable pathology is intriguing.
      Furthermore, the risk spectrum of transfusion-associated macrochimerism and TA
      GVHD in solid organ transplant recipients with and without the complication of
      SOT-GVHD is unknown and warrants further study.

PMID- 18631171
TI  - Balance between vasoconstriction and enhanced oxygen delivery.
AB  - BACKGROUND: Hemoglobin (Hb) solutions are potential alternatives to blood
      transfusion when native oxygen (O(2))-carrying capacity is lacking. Polymerized
      bovine Hb (PBH) solutions are characterized by its vasoactivity, low O(2)
      affinity, oncotic effect, prolonged shelf life, and stability. Responses to
      facilitated O(2) transport, after exchange transfusion with PBH, were studied in
      the hamster window chamber model during acute extreme anemia to determine how PBH
      affects microvascular perfusion and tissue oxygenation. STUDY DESIGN AND METHODS:
      An anemic state was induced by hemodilution with a plasma expander (70-kDa
      dextran). After hemodilution, animals were randomly assigned to exchange
      transfusion groups based on the concentration of PBH used, namely, PBH at 13
      g(Hb) per dL (PBH13), PBH diluted to 8 or 4 g(Hb) per dL in albumin solution at
      matching colloidal osmotic pressure (COP; PBH8 and PBH4), and no PBH only albumin
      solution at matching COP (PBH0). Measurement of systemic variables, microvascular
      hemodynamics, capillary perfusion, and intravascular and tissue O(2) levels was
      performed at 11 percent Hct. RESULTS: Restitution of O(2)-carrying capacity with
      PBH13 restored higher arterial pressure and triggered vasoconstriction, low
      perfusion, and higher peripheral resistance. Groups PBH4 and PBH0 had lower
      arterial pressures than Group PBH13. Groups PBH4 and PBH8 maintained higher
      perfusion and functional capillary density than Groups PBH13 and PBH0. In all
      groups, blood gas variables and acid-base balance were recovered proportional to
      microvascular perfusion. Arterial O(2) tensions were improved for Groups PBH4 and
      PBH8 by preventing O(2) precapillary release and increasing O(2) reserve.
      CONCLUSION: Further studies to establish acellular Hb optimal dosage, efficacy,
      safety, and effects on outcome are indicated before these solutions are
      implemented in routine practice.

PMID- 18631172
TI  - Haematological values from a Gambian cohort--possible reference range for a West
      African population.
AB  - The objective of this study was to establish haematological reference ranges for
      the West African subregion using a Gambian cohort. We analysed full blood counts
      from 1279 subjects aged > or =1 year. Anthropometric and body composition
      measurements were performed. Haematological mean values, medians and 90%
      reference values were calculated and related to malnutrition in children and
      thinness and/or obesity in adults. Haemoglobin (Hb) and mean corpuscular volume
      (MCV) significantly increased with age (P < 0.00001). There were gender-related
      changes in Hb from 15 years of age (P = 0.001) and for MCV only in adults (P =
      0.0002). Hb was significantly reduced in underweight and stunted children (P =
      0.0001 and 0.0002, respectively) but was unaffected by thinness or obesity in
      adults. White blood cell (WBC) and platelet counts were highest under 5 years and
      declined significantly with age (P < 0.0001 and 0.0001). While, there were no
      gender-related differences with WBC, there were higher WBC counts in underweight
      (P = 0.0001) and stunted (P < 0.0001) children. Adult females had significantly
      higher mean platelet counts compared with males (P = 0.006). The mean and median
      values of haematological parameters in The Gambia are similar to other standards
      but the 90% reference range for each parameter encompasses lower values when
      compared with Western standards.

PMID- 18631173
TI  - A novel mechanism of TGFbeta-induced actin reorganization mediated by Smad
      proteins and Rho GTPases.
AB  - In previous studies, we have demonstrated that RhoA/B-dependent signaling
      regulates TGFbeta-induced rapid actin reorganization in Swiss 3T3 fibroblasts.
      Here we report that TGFbeta regulates long-term actin remodeling by increasing
      the steady-state mRNA levels of the RhoB gene in mouse Swiss 3T3 fibroblasts and
      human hepatoma HepG2 cells. We show that this regulation is specific for the RhoB
      gene and is facilitated by enhanced activity of the RhoB promoter. Adenovirus
      mediated gene transfer of Smad2 and Smad3 in Swiss 3T3 fibroblasts induced
      transcription of the endogenous RhoB gene but not the RhoA gene. Interestingly,
      in JEG-3 choriocarcinoma cells that lack endogenous Smad3, TGFbeta-induced
      transcriptional up-regulation of the RhoB gene was not observed, but it was
      restored by adenoviral Smad3 overexpression. In addition, Smad2 and Smad3
      triggered activation of RhoA and RhoB GTPases and long-term actin reorganization
      in Swiss 3T3 fibroblasts. Finally, Smad3, and to a lesser extent Smad2, induced
      transcription of the alpha-smooth muscle actin (alpha-SMA) gene, and enhanced the
      incorporation of alpha-SMA into microfilaments in Swiss 3T3 fibroblasts. These
      data reveal a novel mechanism of cross-talk between the classical TGFbeta/Smad
      pathway and Rho GTPases, regulating the rapid and the long-term actin
      reorganization that may control the fibroblast-myofibroblast differentiation
      program.

PMID- 18631174
TI  - Biological control against bacterial wilt and colonization of mulberry by an
      endophytic Bacillus subtilis strain.
AB  - Forty-five bacterial isolates were collected from surface-sterilized leaves of
      mulberry (Morus alba L.). By screening their antagonistic activities against
      Ralstonia solanacearum in vitro, four isolates showed a remarkable inhibitory
      effect. The evaluation of the antagonistic strains against bacterial wilt of
      mulberry indicated that the strain Lu144 effectively reduced disease incidence.
      In the greenhouse, Lu144 displayed effective biological control against bacterial
      wilt of mulberry when it was applied to sterile or nonsterile soil before the
      infection by the pathogen. Based on bacteriological properties and 16S rRNA gene
      sequencing, Lu144 was identified as a strain of Bacillus subtilis. The endophytic
      population and infection process of Lu144 in mulberry seedlings was explored
      following recovery of the green fluorescent protein (GFP)-labeled Lu144 and
      examination of the labeled strain by confocal laser scanning microscopy.
      Interestingly, the infection of GFP-labeled Lu144 cells into the mulberry
      seedlings occurred through the cracks formed at the lateral root junctions and
      the zone of differentiation and elongation, and the cells were able to develop
      and transfer in mulberry and mainly in the intercellular spaces of different
      tissues. The population of the GFP-labeled Lu144 inoculant was larger and more
      stable in leaves than that in roots and stems.

PMID- 18631175
TI  - Multiple profiling of soil microbial communities identifies potential genetic
      markers of metal-enriched sewage sludge.
AB  - The long-term impacts of Cu- and Zn-rich sewage sludge additions on the structure
      of the microbial community in a field under pasture were investigated using a
      combination of multiplex-terminal restriction fragment length polymorphism (M
      TRFLP) and T-RFLP profiling approaches. Changes in the community structure of
      bacteria, fungi, archaea and actinobacteria were observed in soils that had
      previously received Cu- (50-200 mg kg(-1) soil) and Zn- (150-450 mg kg(-1) soil)
      rich sewage sludge additions. Changes in the structure of all microbial groups
      measured were observed at Cu and Zn rates below the current EU guidelines (135 mg
      kg(-1) Cu and 300 mg kg(-1) Zn). The response of the fungal community, and to a
      lesser extent the bacterial and archaeal community, to Cu was dose dependent. The
      fungal community also showed a dose-dependent response to Zn, which was not
      observed in the other microbial groups assessed. Redundancy analysis demonstrated
      that individual terminal restriction fragments responded to both Cu and Zn and
      these may have potential as genetic markers of long-term metal effects in soil.

PMID- 18631176
TI  - Improved PCR primers for the detection and identification of arbuscular
      mycorrhizal fungi.
AB  - A set of PCR primers that should amplify all subgroups of arbuscular mycorrhizal
      fungi (AMF, Glomeromycota), but exclude sequences from other organisms, was
      designed to facilitate rapid detection and identification directly from field
      grown plant roots. The small subunit rRNA gene was targeted for the new primers
      (AML1 and AML2) because phylogenetic relationships among the Glomeromycota are
      well understood for this gene. Sequence comparisons indicate that the new primers
      should amplify all published AMF sequences except those from Archaeospora
      trappei. The specificity of the new primers was tested using 23 different AMF
      spore morphotypes from trap cultures and Miscanthus sinensis, Glycine max and
      Panax ginseng roots sampled from the field. Non-AMF DNA of 14 plants, 14
      Basidiomycota and 18 Ascomycota was also tested as negative controls. Sequences
      amplified from roots using the new primers were compared with those obtained
      using the established NS31 and AM1 primer combination. The new primers have much
      better specificity and coverage of all known AMF groups.

PMID- 18631177
TI  - Identification, characterization and regulation of two secreted
      polygalacturonases of the emerging rice pathogen Burkholderia glumae.
AB  - Burkholderia glumae is an emerging seed-borne rice pathogen in many areas around
      the world. Previous studies have demonstrated that B. glumae produces two major
      virulence factors: the phytotoxin toxoflavin and a secreted lipase. This
      synthesis of both of these factors is regulated by an N-acyl homoserine lactone
      (AHL)-dependent, cell-density-dependent quorum-sensing regulation system. This
      study reports the production and secretion of two highly similar endo
      polygalacturonases (designated PehA and PehB) by B. glumae. The two enzymes were
      purified to homogeneity and the corresponding genetic determinants were
      identified and characterized. When either polygalacturonase gene was inactivated,
      B. glumae retained rice virulence comparable to that of the wild-type parent
      strain. Furthermore, the role of AHL-dependent quorum sensing and of plant cell
      wall degradation compounds in their regulation was investigated.

PMID- 18631178
TI  - Evidence for specificity of cultivable bacteria associated with arbuscular
      mycorrhizal fungal spores.
AB  - Bacteria associated with arbuscular mycorrhizal (AM) fungal spores may play
      functional roles in interactions between AM fungi, plant hosts and defence
      against plant pathogens. To study AM fungal spore-associated bacteria (AMB) with
      regard to diversity, source effects (AM fungal species, plant host) and
      antagonistic properties, we isolated AMB from surface-decontaminated spores of
      Glomus intraradices and Glomus mosseae extracted from field rhizospheres of
      Festuca ovina and Leucanthemum vulgare. Analysis of 385 AMB was carried out by
      fatty acid methyl ester (FAME) profile analysis, and some also identified using
      16S rRNA gene sequence analysis. The AMB were tested for capacity to inhibit
      growth in vitro of Rhizoctonia solani and production of fluorescent siderophores.
      Half of the AMB isolates could be identified to species (similarity index 0.6)
      within 16 genera and 36 species. AMB were most abundant in the genera
      Arthrobacter and Pseudomonas and in a cluster of unidentified isolates related to
      Stenotrophomonas. The AMB composition was affected by AM fungal species and to
      some extent by plant species. The occurrence of antagonistic isolates depended on
      AM fungal species, but not plant host, and originated from G. intraradices
      spores. AM fungal spores appear to host certain sets of AMB, of which some can
      contribute to resistance by AM fungi against plant pathogens.

PMID- 18631179
TI  - In situ analysis of the bacterial community associated with the reindeer lichen
      Cladonia arbuscula reveals predominance of Alphaproteobacteria.
AB  - The diversity and spatial pattern of the bacterial community hosted by the shrub
      like reindeer lichen Cladonia arbuscula were investigated by general DNA staining
      and FISH, coupled with confocal laser scanning microscopy (CLSM). Using an
      optimized protocol for FISH using cryosections of small lichen fragments, we
      found about 6 x 10(7) bacteria g(-1) of C. arbuscula. Approximately 86% of
      acridine orange-stained cells were also stained by the universal FISH probe
      EUB338. Using group-specific FISH probes, we detected a dominance of
      Alphaproteobacteria (more than 60% of all bacteria), while the abundance of
      Actinobacteria and Betaproteobacteria was much lower (<10%). Firmicutes were
      rarely detected, and no Gammaproteobacteria were present. Bacterial cells of
      different taxonomic groups are embedded in a biofilm-like, continuous layer on
      the internal surface of the C. arbuscula podetia, mainly occurring in small
      colonies of a few to a few hundred cells. The other parts of the lichen showed a
      lower bacterial colonization. alpha-proteobacterial 16S rRNA genes were amplified
      using total DNA extracts from C. arbuscula and separated by single-strand
      conformation polymorphism (SSCP). Sequencing of excised bands revealed the
      dominance of Acetobacteraceae.

PMID- 18631180
TI  - Poly-3-hydroxybutyrate (PHB) supports survival and reproduction in starving
      rhizobia.
AB  - The carbon that rhizobia in root nodules receive from their host powers both N(2)
      fixation, which mainly benefits the host, and rhizobium reproduction. Rhizobia
      also store energy in the lipid poly-3-hydroxybutyrate (PHB), which may enhance
      rhizobium survival when they are carbon limited, either in nodules or in the soil
      between hosts. There can be a conflict of interest between rhizobia and legumes
      over the rate of PHB accumulation, due to a metabolic tradeoff between N(2)
      fixation and PHB accumulation. To quantify the benefits of PHB to carbon-limited
      rhizobia, populations of genetically uniform rhizobia with high vs. low PHB
      (confirmed by flow cytometry) were generated by fractionating Sinorhizobium
      meliloti via density gradient centrifugation, and also by harvesting cells at
      early vs. late stationary phase. These rhizobia were starved for 165 days. PHB
      use during starvation was highly predictive of both initial reproduction and long
      term population maintenance. Cultured S. meliloti accumulated enough PHB to
      triple their initial population size when starved, and to persist for c. 150 days
      before the population fell below its initial value. During the first 21 days of
      nodule growth, undifferentiated S. meliloti within alfalfa nodules accumulated
      enough PHB to support significant increases in reproduction and survival during
      starvation.

PMID- 18631181
TI  - Exported proteins in probiotic bacteria: adhesion to intestinal surfaces, host
      immunomodulation and molecular cross-talking with the host.
AB  - The group of exported proteins of a bacterium are those proteins that are sorted
      from the cytoplasm to the bacterial surface or to the surroundings of the
      microorganism. In probiotic bacteria, these proteins are of special relevance
      because they might determine important traits such as adhesion to intestinal
      surfaces and molecular cross-talking with the host. Current knowledge about the
      presence and biological relevance of exported proteins produced by the main
      genera of probiotic bacteria in the gastrointestinal environment is reviewed in
      this minireview. As will be seen, some of these proteins are involved in host
      adhesion or are able to modify certain signalization pathways within host cells,
      whereas others are important for the physiology of probiotic bacteria in the
      gastrointestinal tract.

PMID- 18631182
TI  - Alterations in rat gut bacteria and intestinal epithelial cells following
      experimental exposure of antimicrobials.
AB  - The intestinal bacteria are known to play a significant role in intestinal
      homoeostasis and the mucosal immune system. In vitro interactions of Ampicillin
      (0.5-2.0 microg mL(-1)), Amphotericin-B (25-200 microg mL(-1)) and Ciprofloxacin
      (50-500 ng mL(-1)) with Escherichia coli, Pseudomonas sp. (Gram-negative),
      Lactobacillus sp., Staphylococcus sp. (Gram-positive), total mixed population of
      gut bacteria and intestinal epithelial cells were studied. In vitro exposure of
      Ciprofloxacin showed significant dose-dependent inhibition throughout the growth
      phase in bacteria. Similar patterns of concentration-dependent changes in
      membrane transport enzymes and structural constituents, dehydrogenase activity
      associated with respiratory and energy-producing processes and esterase activity
      test linked to the general heterotrophic activity of the cell were observed in
      both bacteria and epithelial cells. The antibiotic effects were in the order of
      Amphotericin-B<Ampicillin<Ciprofloxacin. Validation studies were conducted using
      rat intestinal loops filled with different concentrations of antibiotics and
      incubated for 30 min. In situ changes in epithelial cell membrane enzymes and
      constituents also indicated similar trends as observed following in vitro
      exposures. The findings suggest that these antibiotics exert similar cytotoxic
      effects on intestinal epithelial cells and gut bacteria. Thus, gut bacteria can
      be used for in vitro screening of gastrointestinal-cellular toxicity caused by
      antibiotics.

PMID- 18631183
TI  - Leishmania: origin, evolution and future since the Precambrian.
AB  - This brief review discusses the history of leishmaniasis, considering its origin
      from the Paleoartic, Neoartic or Neotropic. We reassess some of the theories of
      the likely origin of this protozoan since the beginning of life on Earth, passing
      through the Mesozoic and continuing to the appearance of humans. The relationship
      between this parasite or its ancestors, possible vectors and hosts with regard to
      ecological modifications is discussed. Recent molecular techniques have helped to
      elucidate some of the evolutionary questions regarding Leishmania, but have also
      brought doubts about the origin and evolution of this human parasite. PCR has
      been used for studies in the new discipline of paleoparasitology, helping to
      elucidate some of the remaining evolutionary questions. Understanding of this
      global condition is fundamental in determining the best approach to use against
      the parasite, specifically for the development of an efficient vaccine.

PMID- 18631184
TI  - Boesenbergia pandurata (Roxb.) Schltr., Eleutherine americana Merr. and
      Rhodomyrtus tomentosa (Aiton) Hassk. as antibiofilm producing and antiquorum
      sensing in Streptococcus pyogenes.
AB  - Biofilm formation has been demonstrated as a potentially important mechanism
      contributing to antibiotic treatment failure on Streptococcus pyogenes. It could
      play a significant role in recurrent and chronic infections. Boesenbergia
      pandurata (Roxb.) Schltr., Eleutherine americana Merr. and Rhodomyrtus tomentosa
      (Aiton) Hassk. have been previously reported from our laboratory as effective
      agents against S. pyogenes. Therefore, in the present study, we observed the
      effect of these plants on biofilm formation. The bacterial biofilms were
      quantified by safranin staining and absorbance at 492 nm. The results clearly
      demonstrated that all subinhibitory concentrations [1/32-1/2 minimal inhibitory
      concentration (MIC)] of E. americana (7.81-125 microg mL(-1)) and R. tomentosa
      (0.24-7.81 microg mL(-1)) extracts significantly prevented biofilm formation
      while 1/2MIC (7.81 microg mL(-1)) of B. pandurata extract produced this effect.
      The issue of antiquorum sensing of this pathogenic bacterium has been further
      explored. A correlation between antiquorum-sensing and antibiofilm-producing
      activities was demonstrated. Strong inhibition on quorum sensing was displayed
      with the extract of R. tomentosa. Eleutherine americana extract showed partial
      inhibition, while B. pandurata did not show this activity. By contrast, an assay
      of microbial adhesion to hydrocarbon revealed no changes in the cell-surface
      hydrophobicity of the treated organisms. Active organisms with the ability to
      inhibit quorum sensing and biofilm formation are worth studying as they may
      provide complimentary medicine for biofilm-associated infections.

PMID- 18631185
TI  - First report of a mycolactone-producing Mycobacterium infection in fish
      agriculture in Belgium.
AB  - In the past few years, a mycolactone-producing subgroup of the Mycobacterium
      marinum complex has been identified and analyzed. These IS2404-positive species
      cause pathology in frogs and fish. A recently isolated mycobacterial strain from
      a fish in Belgium was analyzed using a variety of molecular methods and the
      results were identical to those obtained from a mycolactone-producing M. marinum
      from Israel.

PMID- 18631186
TI  - Significance of the KlLAC1 gene in glucosylceramide production by Kluyveromyces
      lactis.
AB  - Each of the 12 genes involved in the synthesis of glucosylceramide was
      overexpressed in cells of Kluyveromyces lactis to construct a strain accumulating
      a high quantity of glucosylceramide. Glucosylceramide was doubled by the KlLAC1
      gene, which encodes ceramide synthase, and not by 11 other genes, including the
      KlLAG1 gene, a homologue of KlLAC1. Disruption of the KlLAC1 gene reduced the
      content below the detection level. Heterologous expression of the KlLAC1 gene in
      the cells of Saccharomyces cerevisiae caused the accumulation of ceramide,
      composed of C(18) fatty acid. The KlLAC1 protein preferred long-chain (C(18))
      fatty acids to very-long-chain (C(26)) fatty acids for condensation with
      sphingoid bases and seemed to supply a ceramide moiety as the substrate for the
      formation of glucosylceramide. When the amino acid sequences of ceramide synthase
      derived from eight yeast species were compared, LAC1 proteins from five species
      producing glucosylceramide were clearly discriminated from those of the other
      three species and all LAG1 proteins. The LAC1 protein of K. lactis is the enzyme
      that plays a crucial role in the synthesis of glucosylceramide.

PMID- 18631187
TI  - Tornwaldt's cyst presenting only as occipital headache: a case report.
AB  - Tornwaldt's cyst (sometimes called Thornwaldt's cyst) is a rare cause of
      occipital headache. Owing to the rare occurrence of occipital headache as a
      symptom of Tornwaldt's cyst, if the patient presented only with occipital
      headache, this clinical symptom may be falsely perceived as a sign of neurologic
      disease leading to time-consuming diagnostic examinations that delay the
      establishment of a correct diagnosis.

PMID- 18631189
TI  - Ophthalmoplegic migraine and infundibular dilatation of a cerebral artery.
AB  - Ophthalmoplegic migraine (OM) is a childhood disorder of uncertain etiology
      manifesting recurrent unilateral headache associated with a transitory oculomotor
      (usually IIIrd nerve) palsy. Recent publications emphasize the finding on MRI of
      contrast enhancement in the IIIrd nerve suggesting that OM may be a recurrent
      inflammatory neuropathy. We report the case of a 7-year-old boy with typical
      symptoms of this disorder. Angio MR and Angio CT revealed the presence of an
      infundibular dilatation of a perforating branch of the posterior cerebral artery
      adjacent to the symptomatic IIIrd nerve. We speculate that this and perhaps other
      cases of OM may have a different pathophysiology related to compression of the
      IIIrd nerve by an adjacent vascular structure that could activate the
      trigeminovascular system and produce migrainous pain.

PMID- 18631191
TI  - Gross features of lobular endocervical glandular hyperplasia in comparison with
      minimal-deviation adenocarcinoma and stage Ib endocervical-type mucinous
      adenocarcinoma of the uterine cervix.

PMID- 18631192
TI  - Prognostic significance of histopathological parameters in sentinel nodes of
      melanoma patients.

PMID- 18631193
TI  - Atypical Epstein-Barr virus (EBV) latent protein expression in EBV-associated
      smooth muscle tumours occurring in paediatric transplant recipients.

PMID- 18631194
TI  - Iron-induced mucosal pathology of the upper gastrointestinal tract: a common
      finding in patients on oral iron therapy.
AB  - AIMS: Upper gastrointestinal injury from iron tablets at therapeutic dose is not
      widely recognized. The aim was to document cases of iron-related upper
      gastrointestinal (GI) pathology and to determine frequency of occurrence. METHODS
      AND RESULTS: We prospectively studied patients with iron deficiency anaemia
      undergoing upper GI endoscopy from November 2005 to July 2006. Cases of upper GI
      iron deposition from these and other cases extracted retrospectively between 1999
      and 2006 were examined histopathologically and patient notes were reviewed. In
      the prospective study, 15/160 patients investigated for iron deficiency anaemia
      [16.1% (15/93) of those taking oral iron tablets] had iron deposition noted on
      routine haematoxylin and eosin staining. In this plus the retrospective series,
      59 patients were identified with 64 episodes of iron deposition. Eighty-six
      percent (6/7) with oesophageal iron deposition had associated erosion. Sixty
      three percent (29/46) with gastric iron deposition had erosion and 80% (37/46)
      had reactive gastritis. Duodenal deposition was usually (91%, 10/11) within
      macrophages in villous tips with no erosion. Ninety-eight percent (58/59) of iron
      deposition cases had documented oral iron intake. CONCLUSIONS: Iron deposition in
      the upper GI tract is common in patients taking iron tablets. It is frequently
      associated with mucosal disruption in the oesophagus and stomach.

PMID- 18631195
TI  - Adenoma malignum-like mucinous ovarian carcinoma.

PMID- 18631196
TI  - Differentiating neuroblastoma arising in mediastinal germ cell tumour.

PMID- 18631197
TI  - Mucinous spherulosis of the breast: a case report of a potentially under
      recognized lesion with mammographic and immunohistochemical findings.

PMID- 18631198
TI  - Oestrogen receptor status of breast carcinoma: Allred/H score conversion table.

PMID- 18631199
TI  - Diversity of Escherichia coli O157 in a longitudinal farm study using multiple
      locus variable-number tandem-repeat analysis.
AB  - AIMS: To perform a longitudinal study of the diversity of Escherichia coli O157
      from a ruminant pasture/stream environment using multiple-locus variable-number
      tandem-repeat analysis (MLVA). METHODS AND RESULTS: Samples of faecal droppings
      from grazing ruminants and from an adjacent stream were tested longitudinally for
      E. coli O157 by enrichment and immunomagnetic separation (IMS). Using MLVA, 24
      different profiles were identified from a total of 231 E. coli O157 isolates, of
      which 80 were included in a similarity analysis. Four main clusters with several
      subclusters were observed. Although there was close contact between sheep and
      cattle during the study period, E. coli O157 was surprisingly not detected from
      cattle faeces. CONCLUSIONS: The cluster analysis indicated both unrelated and
      closely related E. coli O157 strains. The choice of loci to target in MLVA is
      important for the subtyping result, as loci with high diversities are essential
      for discriminating between closely related isolates. SIGNIFICANCE AND IMPACT OF
      THE STUDY: There is a lack of data available on the use of MLVA to describe E.
      coli O157 diversity and changes over time in the animal reservoirs and the
      environment. Such data are needed in order to further develop MLVA as a typing
      method.

PMID- 18631200
TI  - Acquired iatrogenic vulvar lymphangioma.

PMID- 18631201
TI  - Hobnail haemangioma associated with a secondary sexual characteristic.

PMID- 18631202
TI  - In-transit filia of a melanoma 37 years after primary excision.

PMID- 18631203
TI  - Nasal natural killer/T-cell lymphoma: report of three cases.

PMID- 18631204
TI  - Parallel correlation of immunofluorescence studies with clinical course in a
      patient with influenza vaccine-induced lymphocytic vasculitis.

PMID- 18631205
TI  - Pachyonychia congenital type 1 and alopecia areata in mother and son -
      pathogenetic association or a simple coexistence?

PMID- 18631206
TI  - Transient acantholytic dermatitis and Parkinson's disease.

PMID- 18631207
TI  - Melasma and pregnancy in southern Brazil.

PMID- 18631208
TI  - The effect of switching from calcineurin inhibitor to sirolimus on the incidence
      of skin cancers in kidney transplant recipients.

PMID- 18631209
TI  - Fixed drug eruption mimicking supraumbilical skin rash: one of rare complication
      of transarterial chemoembolization.

PMID- 18631210
TI  - No fecundity cost of female secondary sexual trait expression in the horned
      beetle Onthophagus sagittarius.
AB  - Typically males bear the products of sexual selection in the form of ornaments
      and/or weapons used to compete for and attract females. Secondary sexual traits
      in females have been thought of as the product of correlated responses to sexual
      selection on males. However, there is increasing phylogenetic evidence that
      female secondary sexual traits can arise independently of selection on males, and
      may be subject to sexual selection. Theoretical models of the evolution of female
      ornamentation via male mate choice have assumed that females suffer a cost of
      ornament expression via reduced fecundity, and hence female ornaments are less
      likely to evolve than male ornaments. In the dung beetle Onthophagus sagittarius,
      there has been an independent evolutionary origin of horns in females that are
      qualitatively different from the horns produced by males. We use this system as a
      model to examine the costs of horn expression for females within a life-history
      context. We identified a longevity cost of reproduction for females that was
      independent of horn expression. Large females lived longer, and after controlling
      for lifespan, had a higher lifetime fecundity, and invested more heavily in
      maternal provisioning than did small females. We found no evidence of a cost to
      females of investment in horns. Rather, the rate of increase in fecundity and
      horn expression with body size were equal, so that absolute horn size provides an
      accurate indicator of body size and maternal quality. The effects we observe were
      independent of female contest competition and/or male mate choice, which were
      excluded in our experimental protocol. However, we speculate on the potential
      functional contributions female horns might make to female fitness.

PMID- 18631211
TI  - The impact of parasite dispersal on antagonistic host-parasite coevolution.
AB  - Coevolving populations of hosts and parasites are often subdivided into a set of
      patches connected by dispersal. Higher relative rates of parasite compared with
      host dispersal are expected to lead to parasite local adaptation. However, we
      know of no studies that have considered the implications of higher relative rates
      of parasite dispersal for other aspects of the coevolutionary process, such as
      the rate of coevolution and extent of evolutionary escalation of resistance and
      infectivity traits. We investigated the effect of phage dispersal on coevolution
      in experimental metapopulations of the bacterium Pseudomonas fluorescens SBW25
      and its viral parasite, phage SBW25Phi2. Both the rate of coevolution and the
      breadth of evolved infectivity and resistance ranges peaked at intermediate rates
      of parasite dispersal. These results suggest that parasite dispersal can enhance
      the evolutionary potential of parasites through provision of novel genetic
      variation, but that high rates of parasite dispersal can impede the evolution of
      parasites by homogenizing genetic variation between patches, thereby constraining
      coevolution.

PMID- 18631212
TI  - QTL mapping of inbreeding-related cold sensitivity and conditional lethality in
      Drosophila melanogaster.
AB  - Inbreeding depression is a central theme within genetics, and is of specific
      interest for researchers within evolutionary and conservation genetics and animal
      and plant breeding. Inbreeding effects are thought to be caused by the joint
      expression of conditional and unconditional deleterious alleles. Whenever the
      expression of deleterious alleles is conditional, this can result in extreme
      environmental sensitivity in certain inbred lineages. Analysis of conditional
      lethal effects can reveal some of the loci that are sensitive to inbreeding. We
      performed a QTL (quantitative trait locus) mapping study of inbreeding-related
      and conditionally expressed lethality in Drosophila melanogaster. The lethal
      effect was triggered by exposure to a cold shock. We used a North Carolina
      crossing Design 3 to establish the mapping population, as well as to estimate the
      average dominance ratio and heritability. We found two QTL on the major autosomes
      carrying recessive lethals that caused male mortality, one of which also affected
      female mortality. More detailed study of these loci will provide information on
      the mechanistic basis and environmental sensitivity of inbreeding depression.

PMID- 18631213
TI  - Morph-ratio variation, population size and female reproductive success in
      distylous Pulmonaria officinalis (Boraginaceae).
AB  - Theory predicts that morph ratios in heterostylous populations are governed by
      negative frequency-dependent selection typically resulting in equal morph ratios
      at equilibrium. Previous work on the distylous perennial herb Pulmonaria
      officinalis, however, showed asymmetric mating between floral morphs and a weak
      self-incompatibility system, with the long-styled morph (L-morph) producing
      significantly higher seed set following intramorph crosses and even selfing than
      the short-styled morph (S-morph), two aspects thought to affect female fecundity
      and morph-ratio variation. Here, we evaluated morph ratios and population size of
      all known P. officinalis populations in the northern part of Belgium. Morph
      ratios deviated significantly from 1:1 (range 0.09-1 L-morph frequency, mean =
      0.58). Relative fecundity of the S-morph (i.e. mean seed set of the S-morph/mean
      seed set of the L-morph) was on average 0.73, was positively related to the
      frequency of the L-morph, and reached 1 (similar levels of female fecundity) at
      an average L-morph frequency of 0.66 in the population. As some small populations
      had the S-morph in majority, our results suggest that local morph ratios are
      influenced both by the relative fecundity of L- and S-morph individuals and by
      stochastic processes in small populations.

PMID- 18631214
TI  - Relative longevity and field metabolic rate in birds.
AB  - Metabolism is a defining feature of all living organisms, with the metabolic
      process resulting in the production of free radicals that can cause permanent
      damage to DNA and other molecules. Surprisingly, birds, bats and other organisms
      with high metabolic rates have some of the slowest rates of senescence begging
      the question whether species with high metabolic rates also have evolved
      mechanisms to cope with damage induced by metabolism. To test whether species
      with the highest metabolic rates also lived the longest I determined the
      relationship between relative longevity (maximum lifespan), after adjusting for
      annual adult survival rate, body mass and sampling effort, and mass-specific
      field metabolic rate (FMR) in 35 species of birds. There was a strongly positive
      relationship between relative longevity and FMR, consistent with the hypothesis.
      This conclusion was robust to statistical control for effects of potentially
      confounding variables such as age at first reproduction, latitude and migration
      distance, and similarity in phenotype among species because of common
      phylogenetic descent. Therefore, species of birds with high metabolic rates
      senesce more slowly than species with low metabolic rates.

PMID- 18631215
TI  - Antipsychotic drugs increase N-acetylaspartate and N-acetylaspartylglutamate in
      SH-SY5Y human neuroblastoma cells.
AB  - N-Acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) are related neuronal
      metabolites associated with the diagnosis and treatment of schizophrenia. NAA is
      a valuable marker of neuronal viability in magnetic resonance spectroscopy, a
      technique which has consistently shown NAA levels to be modestly decreased in the
      brains of schizophrenia patients. However, there are conflicting reports on the
      changes in brain NAA levels after treatment with antipsychotic drugs, which exert
      their therapeutic effects in part by blocking dopamine D(2) receptors. NAAG is
      reported to be an agonist of the metabotropic glutamate 2/3 receptor, which is
      linked to neurotransmitter release modulation, including glutamate release.
      Alterations in NAAG metabolism have been implicated in the development of
      schizophrenia possibly via dysregulation of glutamate neurotransmission. In the
      present study we have used high performance liquid chromatography to determine
      the effects of the antipsychotic drugs haloperidol and clozapine on NAA and NAAG
      levels in SH-SY5Y human neuroblastoma cells, a model system used to test the
      responses of dopaminergic neurons in vitro. The results indicate that the
      antipsychotic drugs haloperidol and clozapine increase both NAA and NAAG levels
      in SH-SY5Y cells in a dose and time dependant manner, providing evidence that NAA
      and NAAG metabolism in neurons is responsive to antipsychotic drug treatment.

PMID- 18631216
TI  - Short-term and eight to 12 months results of a tibial tuberosity advancement as
      treatment of canine cranial cruciate ligament damage.
AB  - OBJECTIVE: To describe the perioperative complications and the six weeks and
      eight to 12 months outcome of cases of canine cranial cruciate ligament damage
      treated with a tibial tuberosity advancement. METHODS: The medical records
      including the six weeks' postoperative re-evaluation and radiographs of dogs with
      a tibial tuberosity advancement (70 operated stifles) were analysed regarding the
      short-term outcome and the recorded complications. A questionnaire for the
      evaluation of the eight to 12 months outcome was sent to the owners and the
      answers tabulated. RESULTS: The complication rate was comparable with previous
      reports of cranial cruciate ligament rupture treated with a tibial tuberosity
      advancement or a tibial plateau leveling osteotomy (TPLO). The most frequent
      complication was a symptomatic late secondary meniscal damage in six cases (8.5
      per cent). These cases were successfully treated with a partial meniscectomy
      during a minimal invasive procedure. The six-week re-evaluation showed advanced
      healing of the tibial crest osteotomies in 94 per cent of the cases and a
      significant reduction of the lameness in all dogs. Eighty-three per cent of the
      owners reported that their dogs are never lame or only after heavy exercise eight
      to 12 months after the tibial tuberosity advancement procedure. Sixty-five per
      cent of the owners stated the overall treatment to be excellent, 28 per cent
      good. CLINICAL SIGNIFICANCE: The six weeks' follow-up examination and the
      questionnaire revealed results of the tibial tuberosity advancement comparable to
      previously published studies, stating that the lameness and the activity level of
      the patients with cranial cruciate ligament disease greatly improved after the
      tibial tuberosity advancement.

PMID- 18631217
TI  - Meningomyelitis in dogs: a retrospective review of 28 cases (1999 to 2007).
AB  - OBJECTIVES: To characterise dogs with meningomyelitis and to compare signalment,
      body temperature and vaccination status to a representative control group.
      METHODS: Dogs with meningomyelitis were identified retrospectively. Signalment,
      history, vaccination status, body temperature, severity of neurological
      dysfunction (modified Frankel score), diagnostic procedures, aetiology, survival
      to discharge and long-term survival were analysed. RESULTS: Affected dogs were
      younger (P<0.05) and more frequently hound or toy breeds (P<0.05) when compared
      with controls. Hound and toy breed dogs less than or equal to three years of age
      had a 13 times higher odds of meningomyelitis compared with other breeds
      (P<0.001). General proprioceptive ataxia, limb paresis and paraspinal
      hyperaesthesia were the most common clinical signs. Meningomyelitis of unknown
      aetiology and granulomatous meningomyelitis were the most common diagnoses. The
      median time to death or continued follow-up in dogs alive at discharge was 213
      days. Meningomyelitis resulted in death or euthanasia in 14 of 28 dogs. Clinical
      signs improved or resolved in seven of 28 dogs. CLINICAL SIGNIFICANCE:
      Meningomyelitis is a differential diagnosis for dogs with clinical signs of
      myelopathy. Young dogs and toy or hound breeds seem to be predisposed. Clinical
      signs of meningomyelitis improve or resolve in some dogs.

PMID- 18631218
TI  - Comparison of measurements of 18 analytes in canine and feline blood samples
      using the in-practice Falcor 350 and the reference KoneLab 30i analysers.
AB  - OBJECTIVES: Falcor 350 (A. Menarini Diagnostics) is a wet-reagent biochemistry
      analyser that is available for in-house use. The aim of this study was to compare
      the results produced by this analyser with those obtained by a wet-reagent
      analyser (KoneLab 30i; Thermo Clinical Labsystems) that served as the reference
      instrument. METHODS: Blood samples from 120 clinical cases (60 dogs and 60 cats)
      were analysed for 18 analytes (urea, creatinine, total proteins, albumin,
      creatine kinase, aspartate aminotransferase, alanine aminotransferase, alkaline
      phosphatase, total bilirubin, amylase, lipase, glucose, triacylglycerol,
      cholesterol, total calcium, phosphate, sodium and potassium) using both the
      reference and Falcor instruments. RESULTS: Good to excellent correlations (r(s)
      value) (canine/feline) were identified for urea (0.87/0.86), creatinine
      (0.96/0.99), total proteins (0.91/0.95), albumin (0.96/0.93), creatine kinase
      (0.98/0.99), aspartate aminotransferase (0.95/0.98), alanine aminotransferase
      (0.99/0.99), alkaline phosphatase (0.99/0.98), total bilirubin in dogs (0.88),
      amylase (0.99/0.87), lipase in dogs (0.88), glucose (0.97/0.98), triacylglycerol
      (0.93/0.97), cholesterol (0.99/0.99), total calcium (0.88/0.89), phosphate
      (0.94/0.97) and potassium (0.96/0.97). The correlations for sodium (0.41/0.61),
      total bilirubin in cats (0.78) and lipase in cats (0.25) were considered
      unacceptable. CLINICAL SIGNIFICANCE: For 13 of the 18 analytes (creatinine, total
      proteins, albumin, creatine kinase, aspartate aminotransferase, alanine
      aminotransferase, amylase, glucose, cholesterol, triacylglycerol, phosphate,
      potassium and urea) in both canine and feline samples, the two instruments
      produce values that are closely related to each other (excellent correlation) and
      are sufficiently similar to allow them to be used interchangeably without the
      need for additional correction factor computations (good agreement). Because of
      differences in the methodologies, the Falcor results for alkaline phosphatase,
      total calcium, sodium, lipase and total bilirubin cannot be used interchangeably
      with those generated by the KoneLab and should be interpreted using reference
      intervals established from the Falcor analyser.

PMID- 18631219
TI  - Comparison of sevoflurane and isoflurane in dogs anaesthetised for clinical
      surgical or diagnostic procedures.
AB  - OBJECTIVES: To assess attributes of sevoflurane for routine clinical anaesthesia
      in dogs by comparison with the established volatile anaesthetic isoflurane.
      METHODS: One hundred and eight dogs requiring anaesthesia for elective surgery or
      diagnostic procedures were studied. The majority was premedicated with 0.03 mg/kg
      of acepromazine and 0.01 mg/kg of buprenorphine or 0.3 mg/kg of methadone before
      induction of anaesthesia with 2 to 4 mg/kg of propofol and 0.5 mg/kg of diazepam.
      They were randomly assigned to receive either sevoflurane (group S, n=50) or
      isoflurane (group I, n=58) in oxygen and nitrous oxide for maintenance of
      anaesthesia. Heart rate, respiratory rate, indirect arterial blood pressure,
      haemoglobin saturation, vaporiser settings, end-tidal carbon dioxide and
      anaesthetic concentration and oesophageal temperature were measured. Recovery was
      timed. Data were analysed using analysis of variance and non-parametric tests.
      RESULTS: Heart rate (85 to 140/minute), respiratory rate (six to 27/minute) and
      systolic arterial blood pressure (80 to 150 mmHg) were similar in the two groups.
      End-tidal carbon dioxide between 30 and 60 minutes (group S 6.4 to 6.6 and group
      I 5.8 to 5.9 per cent) and vaporiser settings throughout (group S 2.1 to 2.9 and
      group I 1.5 to 1.5 per cent) were higher in group S. There was no difference in
      time to head lift (18+/-16 minutes), sternal recumbency (28+/-22 minutes) or
      standing (48+/-32 minutes). No adverse events occurred. CLINICAL SIGNIFICANCE:
      Sevoflurane appeared to be a suitable volatile anaesthetic for maintenance of
      routine clinical anaesthesia in dogs.

PMID- 18631220
TI  - Efficacy and tolerability of once-daily cephalexin in canine superficial
      pyoderma: an open controlled study.
AB  - OBJECTIVES: The aims of this study were to evaluate the efficacy and tolerability
      of oral cephalexin given at 30 mg/kg once daily in dogs with superficial pyoderma
      and to compare them with those of oral cephalexin given at 15 mg/kg twice daily.
      METHODS: Twenty dogs with superficial pyoderma were treated with cephalexin at 30
      to 60 mg/kg orally once daily (group A) and compared with 20 dogs treated at a
      dose of 15 to 30 mg/kg orally twice daily (group B). Dogs were treated until 14
      days after clinical remission. Type and distribution of lesions, pruritus and
      general health status were assessed every 14 days using a numerical scale until
      14 days after treatment discontinuation. Total scores for each evaluation day
      were compared between the two groups as well as time to obtain resolution and
      percentage of relapses. RESULTS: Resolution of superficial pyoderma was obtained
      in all dogs in 14 to 42 days (median 28 days for both groups), with no difference
      between groups. Six dogs experienced vomiting or diarrhoea but did not require
      discontinuation of the treatment. Only one dog (in group A) relapsed nine days
      after treatment discontinuation. CLINICAL SIGNIFICANCE: Once-daily cephalexin is
      as effective as twice-daily cephalexin in the treatment of canine superficial
      pyoderma.

PMID- 18631221
TI  - Lumbar osteosarcoma in a chinchilla (Chinchilla laniger).
AB  - An 11-year-old male chinchilla was presented for investigation of progressive
      weight loss, apathy, anorexia, changes in faecal quality and alopecia on the tip
      of the tail. On clinical examination, a stiffness of the back legs was noted.
      Abdominal palpation revealed a hard immobile, irregular structure in the region
      of the last lumbar vertebrae. Subsequent radiography and ultrasonography
      suggested the presence of neoplasia. The following day the chinchilla was showing
      hindlimb paralysis, and there was severe self-trauma to the distal 5 cm of the
      tail. In view of the rapid clinical deterioration, the chinchilla was euthanased
      with the owner's consent. Macroscopic examination supported the clinical
      suspicion of neoplasia. Histopathological examination revealed a reactive
      osteoblastic osteosarcoma. To the author's knowledge, this is the first report of
      osteosarcoma in chinchillas.

PMID- 18631222
TI  - Vertebral stabilisation and selective decompression for the management of triple
      thoracolumbar disc protrusions.
AB  - Triple adjacent thoracolumbar disc protrusions causing moderate to severe spinal
      cord compression were diagnosed by magnetic resonance imaging in two German
      shepherd dogs with marked paraparesis and pelvic limb ataxia. Both cases were
      managed by selective hemilaminectomy, partial annulectomy and bilateral quadruple
      vertebral body stabilisation using novel canine locking fixation plates (SOP).
      The stabilisation of multiple vertebrae in the thoracolumbar spine was possible
      because the plates could be contoured with six degrees of freedom. Spinal pain
      resolved and neurological function improved in both dogs. Screw breakage was
      evident in one dog five months following surgery.

PMID- 18631223
TI  - Single-phase bone scintigraphy in dogs with obscure lameness.
AB  - OBJECTIVES: To evaluate the diagnostic merits of scintigraphy in dogs with
      clinically obscure lameness origin. METHODS: In 43 dogs, the scintigraphic
      findings were compared with the results of subsequent radiological, computed
      tomography and/or arthroscopic findings and/or additional neurological
      examination. RESULTS: In all dogs, focal increased uptake was found in one or
      more joints or bones. The presence of associated pathology was confirmed by
      radiography, computed tomography and/or arthroscopy of the limb region of
      interest. Additional neurological examination was performed when indicated. In
      cases of elbow pathology, unilateral involvement of the elbow was confirmed with
      computed tomography/arthroscopy in 14 cases, while bilateral increased uptake
      could not be confirmed with radiography or computed tomography in three cases.
      Three dogs showed an increased activity in one joint on the bone scan, while
      computed tomography, arthroscopy or radiography revealed bilateral joint disease.
      Generalised mild increased radionuclide uptake in all joints and bones was
      observed in the lame limb in 15 forelimbs and five hindlimbs. Generalised
      prominent uptake of an entire limb was noted in three cases suffering from
      neurological disease. CLINICAL SIGNIFICANCE: Scintigraphy may provide information
      on areas of increased radionuclide uptake, thereby aiding in the localisation of
      obscure lameness. Generalised mild increased uptake of radionuclide in all joints
      and bones in the lame limb may occur in the older dog. The generalised prominent
      uptake, seen in three cases with neurological disease, may resemble reflex
      sympathetic dystrophy syndrome seen in human beings.

PMID- 18631224
TI  - Protothecal granulomatous meningoencephalitis in a dog.
AB  - A case of central nervous system protothecosis in a dog is reported. A three-year
      old male Maremma sheepdog was referred with a two month history of diarrhoea
      associated with progressive tetraparesis, depression and right circling. Stupor,
      severe proprioceptive deficits, bilateral decreased thoracic limb flexor reflexes
      and bilateral deficit of the menace reaction were detected on neurological
      examination and a multi-focal neurological localisation was suspected.
      Histopathological evaluation revealed multi-focal granulomatous foci in the
      thalamus, hippocampus and caudal brainstem containing numerous oval-rounded
      organisms with a thick, periodic acid-Schiff-positive and Gomori's methenamine
      silver-positive cell wall, a basophilic cytoplasm and one nucleus. Scattered
      sporangia containing two to four endospores were also observed. Morphological
      features were consistent with Prototheca species. Ultrastructurally, numerous
      degenerated algae were present within macrophages mainly lacking nuclei and
      cytoplasmic organelles. Generally, protothecosis in dogs is characterised by
      systemic signs because of a multi-organ involvement, and haemorrhagic colitis or
      ophthalmologic signs are the most frequent presenting signs. However,
      protothecosis should be added, also in Europe, to the list of the differential
      diagnoses in adult dogs with a multi-focal neurological localisation even in
      absence of other clinical signs.

PMID- 18631225
TI  - Chiari-like malformation and syringomyelia in normal cavalier King Charles
      spaniels: a multiple diagnostic imaging approach.
AB  - OBJECTIVES: The objectives of the study were (1) to report the incidence of
      Chiari-like malformation and syringomyelia in a normal French cavalier King
      Charles spaniel breeding population; (2) to precise the standard computed
      tomography dimensions of the caudal fossa and (3) to investigate the use of
      ultrasonography in diagnosis of this syndrome. METHODS: Clinically normal adult
      cavalier King Charles spaniel underwent ultrasonographic examination of the
      spinal cord and caudal fossa. Computed tomography was used to measure the caudal
      fossa and magnetic resonance imaging allowed syringomyelia and cerebellar
      herniation identification. RESULTS: Of the 16 dogs in the study, seven had
      syringomyelia (43.7 per cent). All dogs had cerebellar herniation, suggesting
      Chiari-like malformation and also a tendency to occipital dysplasia. Computed
      tomography measurements of the caudal fossa are reported. In one dog, a syrinx
      was identified by ultrasonography. The only difference between dogs with or
      without syringomyelia was that dogs with Chiari-like malformation/syringomyelia
      were statistically older. CLINICAL SIGNIFICANCE: The incidence of Chiari-like
      malformation and syringomyelia may be high in an asymptomatic population of
      cavalier King Charles spaniel . Computed tomography measurements reported in this
      study should now be compared with those of a symptomatic population to evaluate
      the hypothesis that dogs with Chiari-like malformation/syringomyelia syndrome
      have a smaller caudal fossa. This study did not identify a smaller caudal fossa
      in an asymptomatic cavalier King Charles spaniel population with syringomyelia.
      Ultrasonography probably has a low sensitivity for diagnosis of Chiari-like
      malformation/syringomyelia.

PMID- 18631226
TI  - Localised radiotherapy for a ferret with possible anal sac apocrine
      adenocarcinoma.
AB  - A seven-year-old, neutered male ferret was referred to our hospital with two
      perianal masses (2.4x3.0 and 2.4x3.5 cm, respectively) that had recurred after
      initial surgical excision. Complete resection of the masses was impossible as
      there was deep invasion along the rectum. On histopathology, the masses were
      diagnosed as apocrine adenocarcinoma possibly of anal gland origin based on
      tumour location. There was marked response to localised radiotherapy using an
      orthovoltage unit at 4 Gy, twice weekly. No visible mass was detectable after six
      doses of radiation. However, at that time, pleural effusion was diagnosed and
      radiotherapy was discontinued. Cytology of a sample of the pleural effusion
      suggested mesothelioma, and no obvious pulmonary metastasis of anal sac
      adenocarcinoma were identified on thoracic radiography. The ferret died at home
      on day 71 after the first admission.

PMID- 18631227
TI  - Hemifacial spasm associated with an intracranial mass in two dogs.
AB  - Two dogs were presented with hemifacial spasm. Computed tomography images of both
      the dogs revealed an intracranial mass. In the first dog, a lesion at the level
      of the medulla oblongata was thought to cause primary irritation of the facial
      nucleus, with consequently permanent contraction of the ipsilateral facial
      muscles. In the second dog, a mass seemingly arising from the middle cranial
      fossa presumably isolated the facial motor neurons from upper motor neuron
      control, which resulted in hemifacial spasm as a result of loss of inhibitory
      interneuronal activity.

PMID- 18631228
TI  - Anticonvulsant responsive, episodic movement disorder in a German shorthaired
      pointer.
AB  - An episodic movement disorder is described in a young German shorthaired pointer.
      Movement disorders are rare, but well-described, neurological conditions in human
      beings. An attempt is made to classify this disorder using current human
      guidelines. Unlike previously described movement disorders in dogs, this case
      responded very well to two commonly used anticonvulsant therapies, suggesting
      that trial therapy with these drugs is worthwhile in similar cases.

PMID- 18631229
TI  - Passive, opportunistic wildlife disease surveillance in the Rocky Mountain
      Region, USA.
AB  - Wild animals can play an important role in the epidemiology of infectious disease
      with significant public health, economic and ecological consequences. As it is
      often challenging to conduct unbiased surveillance in free-ranging mammal
      populations, passive, opportunistic case identification has been widely used for
      detection of disease events in wild animals. This study evaluated the role of
      different agencies and organizations in the Rocky Mountain Region of the USA to
      identify significant wildlife health events or aggregate information from
      multiple sources. Overall wildlife rehabilitators were in contact with the
      greatest number of animals; however, the data from these groups, in its current
      state, are insufficient for surveillance purposes. Wild animal data from all
      survey groups aggregated at the level of state wildlife organizations; these
      agencies are therefore central in this type of surveillance activity and require
      sufficient resources to ensure that appropriate testing is conducted.

PMID- 18631230
TI  - Post-weaning multisystemic wasting syndrome and other PCV2-related problems in
      pigs: a 12-year experience.
AB  - Post-weaning multisystemic wasting syndrome (PMWS) and other porcine circovirus
      type 2 (PCV2)-related diseases have been reported throughout the world for about
      10 years. The present paper reviews the knowledge acquired in different fields
      and is largely based on the authors' experience. The horizontal transmission of
      PCV2 is widely documented. Contact between pigs is the main route of transmission
      for both PCV2 and PMWS. However, experimental inoculation of PCV2 to pigs does
      not give consistent results and severe clinical signs as encountered in the field
      are rarely obtained. It is thus acknowledged that additional conditions are
      required for the disease to be severe in growing pigs. These are not all known
      but co-infections are thought to act as triggers. The spread of such
      triggers/enhancers, which may or may not be infectious, could have played a role
      in PMWS dissemination via normal national and international trade, in some cases
      conferring an epidemic pattern to this spread. Most of the risk factors
      identified in surveys relate to poor biosecurity and inadequate
      hygiene/husbandry/herd management. The good correlation between viral burden in
      the tissues and disease severity emphasized the role of infection pressure.
      Genomic analysis showed great similarities between PCV2 isolates. However,
      although two main genotypes (genogroups) could be distinguished from the
      phylogenic trees, and changes with time, no clear relationship with strain
      virulence was apparent. Isolates detected in PMWS-positive pigs could also be
      detected in healthy pigs from healthy farms. A strong sow effect was observed in
      disease expression in the offspring. Colostrum composition and colostrum intake
      are supposed to be key components of disease expression. Medication is relatively
      inefficient as a control measure. Commercial PCV2 vaccines are now becoming
      available. However, losses as a result of PMWS and PCV2-related diseases are
      greatly reduced by applying appropriate hygiene and husbandry practices.

PMID- 18631231
TI  - Herd reproduction ratio and time-space analysis of a foot-and-mouth disease
      epidemic in Peru in 2004.
AB  - The herd reproductive ratio (Rh) and spatio-temporal clustering were estimated in
      the 2004 foot-and-mouth disease (FMD) epidemic in Peru. The epidemic lasted 39
      days and involved 26 herds. Movement of cattle was restricted, all susceptible
      species within a 25-km buffer zone were revaccinated, and infected animals with
      clinical signs of FMD were killed or destroyed to control and eradicate the
      disease. The Rh declined from 5.3 on the second day of the epidemic to 1.31 on
      the 25th day. Spatio-temporal clustering of cases was detected at a critical
      distance of 0.5 km and critical times of 7 and 14 days. Cases were clustered in
      space (P=0.006) but not in time (P=0.498). The space-time scan method detected a
      spatio-temporal cluster that included consecutive case numbers 13, 14 and 15,
      located at the temporal midpoint of the epidemic. The values estimated for Rh and
      the cluster analyses provide quantitative estimates of the self-limiting nature
      of FMD spread in a susceptible but vaccinated population.

PMID- 18631232
TI  - Molecular survey of Rickettsia spp. in sick dogs in Italy.
AB  - The aim of this retrospective study was to investigate the prevalence of
      Rickettsia spp. DNA in the blood of sick dogs from Italy. Canine blood samples
      (n=650) submitted for molecular testing of Rickettsia spp. to a diagnostic
      laboratory from February 2003 to March 2006 were studied. The Rickettsia spp. DNA
      detection was performed by Light Cycler real-time PCR using hybridization probes
      separately conducted with specific primers and probes. The total percentage of
      Rickettsia spp.-positive dog samples was 1.5% (10 out of 650). The percentage of
      Rickettsia spp.-positive dog samples submitted from north, central and southern
      Italy were 0.4% (1/248), 1.4% (3/219) and 3.3% (6/183), respectively. Five out of
      138 dogs (3.6%) from Sicily were positive on Rickettsia PCR testing. A
      statistical difference was found between the percentages of positive samples from
      the Yorkshire terrier group (10.7%) compared with the mixed breed group (0.7%).
      No statistical differences were found between seasonal period, region and gender.
      Based on molecular data, there is infrequent rickettsiemia in dogs.

PMID- 18631233
TI  - A network model of H5N1 avian influenza transmission dynamics in domestic cats.
AB  - Naturally occurring cases of influenza in cats owing to the H5N1 strain have been
      reported in several countries. A cat reservoir of H5N1 in the United States could
      provide an environment for zoonotic disease spread to humans. This scenario was
      the impetus to develop a model to study potential transmission of H5N1 virus in
      domestic cats utilizing information on cat ownership and cat-cat interaction
      patterns, in addition to biological properties of the virus. The roaming
      behaviour of cats significantly influenced epidemic dynamics, as demonstrated by
      the simulation results from this model. A better understanding of the behaviour
      of domestic cats and the H5N1 influenza virus can be used to predict epidemic
      dynamics following the introduction of H5N1 virus into the United States and to
      develop effective strategies to prevent virus transmission to both cats and
      humans.

PMID- 18631234
TI  - The occurrence and anti-microbial susceptibility of Salmonellae isolated from
      commercially available pig ear pet treats.
AB  - In Canada, there have been reported outbreaks of human salmonellosis related to
      exposure to animal-derived pet treats, involving pig ear treats, beef steak patty
      dog treats and pet treats of seafood origin. As a follow-up to recommendations
      made to the pig ear treat industry in 1999, a total of 245 pig ear treats were
      purchased in two Canadian cities to provide evidence of adoption of the
      recommendations and to determine the current levels of Salmonella contamination
      of pig ear treats available at pet stores. An overall prevalence of 4% was
      observed, with isolates exhibiting resistance to up to seven anti-microbials.
      Serotypes recovered included S. Bovismorbificans, S. Give, S. Derby and S.
      Typhimurium var. Copenhagen. Although the prevalence observed during this study
      is lower than the prevalence observed in 1999, pig ear treats should still be
      considered as a possible source of Salmonella and anti-microbial resistant
      bacteria to humans and dogs in Canada.

PMID- 18631235
TI  - Discussion of the Compendium of Veterinary Standard Precautions: preventing
      zoonotic disease transmission in veterinary personnel.
AB  - Veterinary practices are unique environments that bring humans into close contact
      with many different species of animals; therefore, the risk of exposure to
      infectious pathogens is inherently different in veterinary medicine than in human
      medicine. In contrast to the risk of exposure to blood in human medicine,
      infections from zoonotic diseases in veterinary personnel are primarily related
      to exposure to animal faeces, infected skin, wounds, droplets and puncture
      wounds. Infection-control measures in veterinary practices are often insufficient
      to prevent zoonotic disease transmission. The Veterinary Standard Precautions
      (VSP) Compendium is designed to help prevent transmission of zoonotic pathogens
      from animal patients to veterinary personnel in private practice.

PMID- 18631236
TI  - Serological survey for antibodies to Leptospira in dogs and raccoons in
      Washington State.
AB  - A high number of reported canine leptospirosis cases occurred in Washington State
      from 2004 to 2006. This prompted a serosurvey of healthy dogs from around the
      state to determine the distribution of exposure risk and to provide insight into
      serovar epidemiology in the region. In addition, a convenience sample of sera
      from injured raccoons was also tested, and clinical serological data from the
      Washington Animal Disease Diagnostic Laboratory were examined. The proportion of
      dogs with an antibody titre (>or=1:100) to any serovar was 27/158 (17.1%, 95% CI
      11.6-23.9), and that proportion among raccoons was 22/115 (19.1%, 95% CI 12.4
      27.5) suggesting that the potential for exposure in Washington state is not
      uncommon. The most frequently detected serovars in healthy dogs were Autumnalis,
      Icterohemorrhagiae and Canicola, in clinical canine samples Autumnalis,
      Bratislava and Pomona were more frequent and in sick or injured raccoons
      Autumnalis, and Pomona were most frequently detected. Clinical canine serology
      demonstrated a late summer-fall seasonality that was consistent with other
      reports. An outbreak of canine leptospirosis occurred during 2004-2006 and was
      located primarily in western Washington counties, as were three reported human
      cases in 2005. Canine leptospirosis surveillance is an important tool for
      detecting human risk of exposure and may provide insights into which serovars are
      currently of clinical importance.

PMID- 18631237
TI  - The periplasmic regulator ExoR inhibits ExoS/ChvI two-component signalling in
      Sinorhizobium meliloti.
AB  - Sinorhizobium meliloti requires ExoS/ChvI two-component signalling to establish a
      nitrogen-fixing symbiosis with legume hosts. The importance of ExoS/ChvI
      signalling in microbe-host interactions is underscored by the requirement of
      ExoS/ChvI orthologues for virulence of the related alpha-proteobacteria
      Agrobacterium tumefaciens and Brucella abortus. In S. meliloti, ExoS/ChvI is a
      key regulator of gene expression for exopolysaccharide synthesis, biofilm
      formation, motility, nutrient utilization and free-living viability. Previously,
      we showed that the novel conserved regulator ExoR interacts genetically with both
      ExoS and ChvI, and localizes to the periplasm of S. meliloti. Here, we show that
      ExoR physically associates with ExoS and that this association is important for
      regulating ExoS/ChvI signalling. We have identified point mutations in the Sel1
      like repeat region of ExoR that disrupt binding to ExoS and cause a dramatic
      increase in ExoS/ChvI-dependent gene expression. Furthermore, we have found that
      physical interaction with ExoS stabilizes the ExoR protein. Together, our results
      indicate that ExoR binds to ExoS in the periplasm of S. meliloti to inhibit
      ExoS/ChvI activity, and that ExoR represents a novel periplasmic inhibitor of two
      component signalling.

PMID- 18631238
TI  - Characterization of the NapGH quinol dehydrogenase complex involved in Wolinella
      succinogenes nitrate respiration.
AB  - Nitrate respiration catalysed by the epsilon-proteobacterium Wolinella
      succinogenes relies on the NapAGHBFLD system that comprises periplasmic nitrate
      reductase (NapA) and various other Nap proteins required for electron transport
      from menaquinol to NapA or maturation of Nap components. The W. succinogenes Nap
      system is unusual as electron transfer to NapA was shown previously to depend on
      both subunits of the predicted menaquinol dehydrogenase complex NapGH but did not
      require a cytochrome c of the NapC/NrfH family. Nonetheless, minor residual
      growth by nitrate respiration was observed in napG and napH gene inactivation
      mutants. Here, the question is addressed whether alternative membrane-bound
      menaquinol dehydrogenases, like NrfH and NosGH, involved in nitrite or N2O
      reduction systems, are able to functionally replace NapGH. The phenotypes of
      various gene deletion mutants as well as strains expressing chimeric nap/nos
      operons demonstrate that NosH is able to donate electrons to the respiratory
      chain of nitrate respiration at a physiologically relevant rate, whereas NrfH and
      NosG are not. The iron-sulphur protein NapG was shown to form a complex with NapH
      in the membrane but was detected in the periplasmic cell fraction in the absence
      of NapH. Likewise, NosH is able to bind NapG. Each of the eight poly-cysteine
      motifs present in either NapG or NapH was shown to be essential for nitrate
      respiration. The NapG homologue NosG could not substitute for NapG, even after
      adjusting the cysteine spacing to that of NapG, implying that NapG and NosG are
      specific adapter proteins that channel electrons into either the Nap or Nos
      system. The current model on the structure and function of the NapGH menaquinol
      dehydrogenase complex is presented and the composition of the electron transport
      chains that deliver electrons to periplasmic reductases for either nitrate,
      nitrite or N2O is discussed.

PMID- 18631239
TI  - Characterization of CetA and CetB, a bipartite energy taxis system in
      Campylobacter jejuni.
AB  - The energy taxis receptor Aer, in Escherichia coli, senses changes in the redox
      state of the electron transport system via an flavin adenine dinucleotide
      cofactor bound to a PAS domain. The PAS domain (a sensory domain named after
      three proteins Per, ARNT and Sim, where it was first identified) is thought to
      interact directly with the Aer HAMP domain to transmit this signal to the highly
      conserved domain (HCD) found in chemotaxis receptors. An apparent energy taxis
      system in Campylobacter jejuni is composed of two proteins, CetA and CetB, that
      have the domains of Aer divided between them. CetB has a PAS domain, while CetA
      has a predicted transmembrane region, HAMP domain and the HCD. In this study, we
      examined the expression of cetA and cetB and the biochemical properties of the
      proteins they encode. cetA and cetB are co-transcribed independently of the
      flagellar regulon. CetA has two transmembrane helices in a helical hairpin while
      CetB is a peripheral membrane protein tightly associated with the membrane. CetB
      levels are CetA dependent. Additionally, we demonstrated that both CetA and CetB
      participate in complexes, including a likely CetB dimer and a complex that may
      include both CetA and CetB. This study provides a foundation for further
      characterization of signal transduction mechanisms within CetA/CetB.

PMID- 18631240
TI  - Recombination of synthetic oligonucleotides with prokaryotic chromosomes:
      substrate requirements of the Escherichia coli/lambdaRed and Sulfolobus
      acidocaldarius recombination systems.
AB  - In order to reveal functional properties of recombination involving short ssDNAs
      in hyperthermophilic archaea, we evaluated oligonucleotide-mediated
      transformation (OMT) in Sulfolobus acidocaldarius and Escherichia coli as a
      function of the molecular properties of the ssDNA substrates. Unmodified ssDNAs
      as short as 20-22 nt yielded recombinants in both organisms, as did longer DNAs
      forming as few as 2-5 base pairs on one side of the genomic mutation. The two OMT
      systems showed similar responses to certain end modifications of the
      oligonucleotides, but E. coli was found to require a 5' phosphate on 5'-limited
      ssDNA whereas this requirement was not evident in S. acidocaldarius. The ability
      of both E. coli and S. acidocaldarius to incorporate short, mismatched ssDNAs
      into their genomes raises questions about the biological significance of this
      capability, including its phylogenetic distribution among microorganisms and its
      impact on genome stability. These questions seem particularly relevant for S.
      acidocaldarius, as this archaeon has natural competence for OMT, encodes no MutSL
      homologues and thrives under environmental conditions that accelerate DNA
      decomposition.

PMID- 18631242
TI  - AglF, aglG and aglI, novel members of a gene island involved in the N
      glycosylation of the Haloferax volcanii S-layer glycoprotein.
AB  - Proteins in all three domains of life can experience N-glycosylation. The steps
      involved in the archaeal version of this post-translational modification remain
      largely unknown. Hence, as the next step in ongoing efforts to identify
      components of the N-glycosylation pathway of the halophilic archaeon Haloferax
      volcanii, the involvement of three additional gene products in the biosynthesis
      of the pentasaccharide decorating the S-layer glycoprotein was demonstrated. The
      genes encoding AglF, AglI and AglG are found immediately upstream of the gene
      encoding the archaeal oligosaccharide transferase, AglB. Evidence showing that
      AglF and AglI are involved in the addition of the hexuronic acid found at
      position three of the pentasaccharide is provided, while AglG is shown to
      contribute to the addition of the hexuronic acid found at position two. Given
      their proximities in the H. volcanii genome, the transcription profiles of aglF,
      aglI, aglG and aglB were considered. While only aglF and aglI share a common
      promoter, transcription of the four genes is co-ordinated, as revealed by
      determining transcript levels in H. volcanii cells raised in different growth
      conditions. Such changes in N-glycosylation gene transcription levels offer
      additional support for the adaptive role of this post-translational modification
      in H. volcanii.

PMID- 18631241
TI  - System-level mapping of Escherichia coli response regulator dimerization with
      FRET hybrids.
AB  - SUMMARY: Two-component signal transduction, featuring highly conserved histidine
      kinases (HKs) and response regulators (RRs), is one of the most prevalent
      signalling schemes in prokaryotes. RRs function as phosphorylation-activated
      switches to mediate diverse output responses, mostly via transcription
      regulation. As bacterial genomes typically encode multiple two-component proteins
      for distinct signalling pathways, the sequence and structural similarities of RR
      receiver domains create significant challenges to maintain interaction
      specificity. It is especially demanding for members of the OmpR/PhoB subfamily,
      the largest RR subfamily, which share a conserved dimerization interface for
      phosphorylation-mediated transcription regulation. We developed a strategy to
      investigate RR interaction by analysing Forster resonance energy transfer (FRET)
      between cyan fluorescent protein (CFP)- and yellow fluorescent protein (YFP)
      fused RRs in vitro. Using the Escherichia coli RR PhoB as a model system, we were
      able to observe phosphorylation-dependent FRET between fluorescent protein (FP)
      PhoB proteins and validated the FRET method by determining dimerization affinity
      and dimerization-coupled phosphorylation kinetics that recapitulated values
      determined by alternative methods. Further application of the FRET method to all
      E. coli OmpR/PhoB subfamily RRs revealed that phosphorylation-activated RR
      interaction is indeed a common theme for OmpR/PhoB subfamily RRs and these RRs
      display significant interaction specificity. Weak hetero-pair interactions were
      also identified between several different RRs, suggesting potential cross
      regulation between distinct pathways.

PMID- 18631243
TI  - Cloning and characterization of an acyl-CoA-dependent diacylglycerol
      acyltransferase 1 (DGAT1) gene from Tropaeolum majus, and a study of the
      functional motifs of the DGAT protein using site-directed mutagenesis to modify
      enzyme activity and oil content.
AB  - SUMMARY: A full-length cDNA encoding a putative diacylglycerol acyltransferase 1
      (DGAT1, EC 2.3.1.20) was obtained from Tropaeolum majus (garden nasturtium). The
      1557-bp open reading frame of this cDNA, designated TmDGAT1, encodes a protein of
      518 amino acids showing high homology to other plant DGAT1s. The TmDGAT1 gene was
      expressed exclusively in developing seeds. Expression of recombinant TmDGAT1 in
      the yeast H1246MATalpha quadruple mutant (DGA1, LRO1, ARE1, ARE2) restored the
      capability of the mutant host to produce triacylglycerols (TAGs). The recombinant
      TmDGAT1 protein was capable of utilizing a range of (14)C-labelled fatty acyl-CoA
      donors and diacylglycerol acceptors, and could synthesize (14)C-trierucin.
      Collectively, these findings confirm that the TmDGAT1 gene encodes an acyl-CoA
      dependent DGAT1. In plant transformation studies, seed-specific expression of
      TmDGAT1 was able to complement the low TAG/unusual fatty acid phenotype of the
      Arabidopsis AS11 (DGAT1) mutant. Over-expression of TmDGAT1 in wild-type
      Arabidopsis and high-erucic-acid rapeseed (HEAR) and canola Brassica napus
      resulted in an increase in oil content (3.5%-10% on a dry weight basis, or a net
      increase of 11%-30%). Site-directed mutagenesis was conducted on six putative
      functional regions/motifs of the TmDGAT1 enzyme. Mutagenesis of a serine residue
      in a putative SnRK1 target site resulted in a 38%-80% increase in DGAT1 activity,
      and over-expression of the mutated TmDGAT1 in Arabidopsis resulted in a 20%-50%
      increase in oil content on a per seed basis. Thus, alteration of this putative
      serine/threonine protein kinase site can be exploited to enhance DGAT1 activity,
      and expression of mutated DGAT1 can be used to enhance oil content.

PMID- 18631244
TI  - Toxoplasma gondii uses unusual sorting mechanisms to deliver transmembrane
      proteins into the host-cell vacuole.
AB  - A critical step in infection by the apicomplexan parasite Toxoplasma gondii is
      the formation of a membrane-bound compartment within which the parasite
      proliferates. This process relies on a set of secretory organelles that discharge
      their contents into the host cell upon invasion. Among these organelles, the
      dense granules are specialized in the export of transmembrane (TM) GRA proteins,
      which are major components of the mature parasitophorous vacuole (PV) membrane.
      How eukaryotic pathogens export and sort membrane-bound proteins destined for the
      host cell is still poorly understood at the mechanistic level. In this study, we
      show that soluble trafficking of the PV-targeted GRA5 TM protein is parasite
      specific: when expressed in mammalian cells, GRA5 is targeted to the plasma
      membrane and behaves as an integral membrane protein with a type I toplogy. We
      also demonstrate the dual role of the GRA5 N-terminal ectodomain, which is
      sufficient to prevent membrane integration within the parasite and is essential
      for both sorting and post-secretory membrane insertion into the vacuolar
      membrane. These results contrast with the general rule that states that
      information contained within the cytoplasmic tail and/or the TM domain of
      integral membrane proteins dictates their cellular localization. They also
      highlight the diversity of sorting mechanisms that leads to the specialization of
      secretory processes uniquely adapted to intracellular parasitism.

PMID- 18631245
TI  - Azithromycin as an adjunctive treatment of aggressive periodontitis: 12-months
      randomized clinical trial.
AB  - AIM: To assess the effect of systemic azithromycin as a supplement to scaling and
      root planing (SRP) in the treatment of aggressive periodontitis (AgP). MATERIAL
      AND METHODS: Twenty-four individuals (13-26 years old) underwent a plaque control
      program, and then were treated with SRP. Subjects were assigned randomly into two
      groups; the test group used 500 mg azithromycin once a day for 3 days, whereas
      the control group used a placebo. Clinical variables were assessed at baseline,
      3, 6, 9, and 12 months. The periodontal status at baseline and 12 months was
      compared using the Wald test, and adjusting for the effect of clustering of teeth
      within subjects. RESULTS: There were no significant differences in visible
      plaque, gingival bleeding, and supragingival calculus between groups throughout
      the study. Periodontal probing depth (PPD) and clinical attachment level improved
      significantly from baseline to 12 months in both groups, with the test group
      showing significantly more reduction in mean PPD compared with controls (2.88 mm
      versus 1.85 mm, respectively, p=0.025). Subjects administering azithromycin
      showed a higher percentage of teeth with attachment gain >or=1 mm (81.34 versus
      63.63, p=0.037), whereas the controls had higher percentage of teeth with
      attachment loss >or=1 mm (11.57 versus 2.24, p=0.015). CONCLUSIONS: The
      adjunctive use of azithromycin has the potential to improve periodontal health of
      young patients with AgP.

PMID- 18631246
TI  - A clinical study evaluating the treatment of supra-alveolar-type defects with
      access flap surgery with and without an enamel matrix protein derivative: a pilot
      study.
AB  - AIM: There is evidence that regenerative treatment of intra-bony and mandibular
      class II furcation defects with access flap and an application of an enamel
      matrix protein derivative (EMD) can result in a clinical benefit compared with
      access flap alone. The aim of this pilot study was to check if the results of
      access flap surgery in suprabony defects are improved by additional application
      of EMD. MATERIAL AND METHODS: Thirty-nine adult subjects with supra-alveolar-type
      defects were randomly assigned to a test (n=25) and a control group (n=14).
      Seventy teeth were treated with EMD; 28 teeth were treated by access flap.
      Probing depth (PD), clinical attachment level and bleeding on probing were
      evaluated at baseline and after 12 months. RESULTS: PD of the operated teeth was
      improved in both groups (p<0.001 to p=0.041) but always better in the test group.
      The attachment gain was 2.72+/-1.80 mm at sites with an initial PD >or=7 mm in
      the test group and 0.78+/-0.62 mm in the control group (p=0.004). In the test
      group the mean attachment gain was 0.97+/-0.92 mm (p<0.001); the mean reduction
      of PD was 1.55+/-0.90 mm (p<0.001). CONCLUSIONS: The data suggest a significant
      clinical benefit of supplementary application of EMD during surgical treatment of
      periodontitis of supra-alveolar pockets, especially in deeper pockets.

PMID- 18631247
TI  - Green tea extract reduces induction of p53 and apoptosis in UVB-irradiated human
      skin independent of transcriptional controls.
AB  - Ultraviolet (UV) irradiation plays a pivotal role in human skin carcinongenesis.
      Preclinically, systemically and topically applied green tea extract (GTE) has
      shown reduction of UV-induced (i) erythema, (ii) DNA damage, (iii) formation of
      radical oxygen species and (iv) downregulation of numerous factors related to
      apoptosis, inflammation, differentiation and carcinogenesis. In humans, topical
      GTE has so far only been tested in limited studies, with usually very high GTE
      concentrations and over short periods of time. Both chemical stability of GTE and
      staining properties of highly concentrated green tea polyphenols limit the
      usability of highly concentrated green tea extracts in cosmetic products. The
      present study tested the utility of stabilized low-dose GTE as
      photochemopreventive agents under everyday conditions. We irradiated with up to
      100 mJ/cm(2) of UVB light skin patches which were pretreated with either OM24
      containing lotion or a placebo lotion. Biopsies were taken from both irradiated
      and un-irradiated skin for both immunohistochemistry and DNA microarray analysis.
      We found that while OM24 treatment did not significantly affect UV-induced
      erythema and thymidine dimer formation, OM24 treatment significantly reduced UV
      induced p53 expression in keratinocytes. We also found that OM24 treatment
      significantly reduced the number of apoptotic keratinocytes (sunburn cells and
      TUNEL-positive cells). Carefully controlled DNA microarray analyses showed that
      OM24 treatment does not induce off-target changes in gene expression, reducing
      the likelihood of unwanted side-effects. Topical GTE (OM24) reduces UVB-mediated
      epithelial damage already at low, cosmetically usable concentrations, without
      tachyphylaxis over 5 weeks, suggesting GTE as suitable everyday
      photochemopreventive agents.

PMID- 18631248
TI  - Polymorphisms within the C3 gene are associated with specific IgE levels to
      common allergens and super-antigens among atopic dermatitis patients.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease. Twin and family
      studies suggest a strong genetic component of the disease. The keratinocytes
      secrete high amounts of C3 after stimulation with pro-inflammatory cytokines,
      which may play a functional role in skin inflammation. In this study, we
      genotyped four different single nucleotide polymorphisms (SNPs) by melting curve
      analysis using sequence specific hybridization probes in a well-characterized
      cohort of AD patients. Among four SNPs within C3 gene, higher frequencies of
      rs10410674 (23.5% vs 12.2%) and rs366510 (13.8% vs 6.5%) were observed in AD
      patients as compared with control group. None of the tested polymorphisms showed
      significant association with the risk of the disease phenotype. Analysis of
      rs10402876 SNP revealed its association with less severe AD disease expression
      (low SCORAD). Total serum IgE levels were not different among AD patients having
      any of the four SNPs. However, we observed significantly less serum-specific IgE
      levels to common allergens (Dermatophagoides pteronyssinus and birch pollens) and
      Staphylococcal enterotoxin B in AD patients having rs366510 SNP. Thus,
      associations of polymorphism within C3 gene with less severe AD disease
      expression and a weaker sensitization to common allergens suggest the role of
      these SNPs in the development of AD.

PMID- 18631249
TI  - Novel sphingolipid derivatives promote keratinocyte differentiation.
AB  - Sphingolipids are important components of the water permeability barrier of the
      skin. Moreover, ceramides were also shown to influence keratinocyte
      differentiation and regulate cellular signalling. A confluence-induced
      differentiation model of normal human keratinocytes was established to allow
      evaluation of pro- and anti-differentiation effects of exogenous compounds. The
      effects of phytosphingosine (PS), sphingosine (SO), sphinganine (SA) and their
      hexanoyl (-C6), stearoyl (-C18) and salicyl (-SLC) derivatives, C12-alkylamine
      salicylate (C12-SLC), salicylate (SLC) along with vitamin D3 (VD3) and retinol as
      control substances were tested in this system. Cytotoxicity assays were carried
      out to optimize the incubation conditions of compounds and whole genome
      expression changes were monitored by DNA-microarray on days 0, 1 and 4. Geometric
      means of gene expression levels of a subset of known keratinocyte differentiation
      related genes were calculated from the microarray data to compare effects of the
      sphingolipid derivatives. Compound treatment-induced transcriptional changes were
      analysed by the ExPlain software (BIOBASE GmbH). Five of the assayed substances
      (SA, SO-C6, PS-C6, SO-SLC, PS-SLC) were found to be potent promoters of
      keratinocyte differentiation compared with VD3, and C12-SLC revealed potential
      anti-differentiation properties. ExPlain analysis found a different regulatory
      profile in the computed transcriptional networks of the sphingoid bases versus
      their -C6 and especially -SLC derivatives suggesting that the change in their
      keratinocyte differentiation modifying potential is due to a unique effect of the
      covalent attachment of the salicylic acid. Taken together, these results
      demonstrate the gene regulatory potential of sphingolipid species that could be
      valuable for dermatological or cosmetic applications.

PMID- 18631250
TI  - Evaluation of PCR primers for universal nifH gene targeting and for assessment of
      transcribed nifH pools in roots of Oryza longistaminata with and without low
      nitrogen input.
AB  - The bias of widely used degenerate nifH-specific primer sets was first tested
      using denaturing gradient gel electrophoresis (DGGE), and their application for
      profiling of complex communities assessed for roots of Oryza longistaminata. When
      primers (P) with mismatches at nondegenerate positions were used on genomic DNA
      of Azotobacter vinelandii, which harbors three single divergent nifH genes,
      template-to-product ratios were highly skewed. In contrast, we obtained no
      evidence for a large PCR bias when we used highly degenerate primers with no
      mismatches (Z). Similar results were obtained for reverse transcription (RT)-PCR
      amplifications from root RNA from O. longistaminata grown at the river bed of the
      Okavango, where Z-primers detected a more complex nifH pool, corroborating that
      the P-primers are quite biased in the nifH sequences they amplify. In microcosms
      of O. longistaminata grown in the phytotron in the presence or absence of
      constant low nitrogen input (25 kg NH4NO3 ha(-1) year(-1)), roots of nitrogen
      treated plants showed similar, slightly higher levels of nifH-mRNA. However,
      nitrogen treatment had a strong effect on the composition and diversity of
      expressed nifH pools that shifted towards methylotroph-related nitrogenases. Thus
      the active population of diazotrophs was not resistant towards low rates of
      nitrogen input and decreased significantly in richness, as also observed for
      plant species richness in grasslands by others.

PMID- 18631251
TI  - Transgenic overexpression of insulin receptor substrate 1 in hepatocytes enhances
      hepatocellular proliferation in young mice only.
AB  - AIM: The insulin receptor substrate-1 (IRS-1) is a multisite docking protein
      which plays a central role in the signal transduction of growth factors such as
      insulin and insulin-like growth factors (IGF-1 and IGF-2). It is found to be
      frequently overexpressed in human hepatocellular carcinoma (HCC). METHODS: To
      study IRS-1 overexpression in hepatocytes in vivo, transgenic mice overexpressing
      IRS-1 exclusively in hepatocytes were created, showing enhanced hepatocyte
      proliferation in young animals. In the present study, the phenotype of IRS-1
      transgenic animals was characterized over a period of two years. The livers of
      transgenic and control mice were analyzed for IRS-1 expression and
      phosphorylation, activation of the downstream mitogen-activated protein kinase
      (MAPK) cascade and phosphatidylinositol 3' kinase (PI3'K) and macroscopical and
      histological abnormalities. RESULTS: The enhanced hepatocyte proliferation
      observed in young IRS-1 transgenic animals was no longer detectable in adult
      mice. Despite constitutive overexpression and phosphorylation of IRS-1, MAPK- and
      IRS-1-associated PI3'K activity were significantly reduced in older transgenic
      mice. Furthermore, no premalignant lesions or HCC were detected in IRS-1
      transgenic animals up to the age of 24 months. CONCLUSIONS: Therefore, additional
      mechanisms such as enhanced growth factor expression or impaired negative
      feedback control mechanisms may augment IRS-1 overexpression in human
      hepatocarcinogenesis.

PMID- 18631252
TI  - Supplement improves nutrition and stresses caused by examination-associated
      fasting in patients with liver cirrhosis.
AB  - AIM: Cirrhotic patients tend to develop malnutrition by fasting, yet the
      importance of nutritional care during examination-associated fasting has not been
      investigated. This study aimed to examine the effects of a nutritional supplement
      on nutrition and stresses caused by examination-associated fasting in cirrhotic
      patients. METHODS: Twenty-nine cirrhotic patients were enrolled in this study. No
      energy was supplied to patients in the fasting group (n = 11) prior to computed
      tomography or magnetic resonance imaging examination. A supplement of 200 kcal
      was given to the patients in the supplement group (n = 18) prior to computed
      tomography or magnetic resonance imaging examination. The effect of the
      supplement on stresses was evaluated by self-rating questionnaire. Changes in
      biochemical parameters were also investigated before and after computed
      tomography or magnetic resonance imaging examinations. RESULTS: There were no
      significant differences in age, sex, body mass index, or liver function tests
      between the two groups at the start of the study. In the supplement group, stress
      scores for physical symptoms (thirst and light-headedness) and mental symptoms
      (hunger, hypodynamia and fatigue) were significantly lower compared to those in
      the fasting group. Also in the supplement group, peripheral 3-hydroxybutyric acid
      and free fatty acids levels were significantly decreased compared to those in the
      fasting group, to within normal ranges. In addition, a decrease in prothrombin
      time was significantly inhibited by intake of the supplement. CONCLUSION: We
      demonstrated that a nutritional supplement improved nutrition and reduced both
      the physical and mental stresses associated with examination-associated fasting
      in cirrhotic patients.

PMID- 18631253
TI  - Efficacy of splenectomy for hypersplenic patients with advanced hepatocellular
      carcinoma.
AB  - AIM: Chemotherapy for advanced hepatocellular carcinoma (HCC) patients with
      hypersplenism is generally unsatisfactory, as a lower-dose therapy is usually
      administered. Splenectomy may represent a better approach to overcoming the
      complication due to hypersplenism in patients with advanced HCC. This
      retrospective study was conducted to evaluate whether HCC patients who undergo
      splenectomy show improved prognosis. METHODS: We examined 34 HCC patients. Twenty
      two had thrombocytopenia and/or leucopenia and underwent laparoscopic
      splenectomy. The completion rate of full-dose drug regimens, the response rate,
      the toxicity of chemotherapy and the cumulative survival rate were compared
      between the splenectomy and non-splenectomy groups. RESULTS: The response rate
      and the cumulative survival rate in the splenectomy group were significantly
      better than that in the non-splenectomy group. CONCLUSIONS: Splenectomy is an
      efficient method for advanced HCC patients with hypersplenism treated by
      chemotherapy.

PMID- 18631254
TI  - Acute administration of sildenafil enhances hepatic cyclic guanosine
      monophosphate production and reduces hepatic sinusoid resistance in cirrhotic
      patients.
AB  - AIM: In liver cirrhosis, the increased production of nitric oxide (NO)
      contributes to increased systemic and splanchnic vasodilatation. The inhibition
      of phosphodiesterase-5 (PDE-5), an enzyme responsible for the degradation of
      cyclic guanosine monophosphate (cGMP), is widely used in the treatment of
      erectile dysfunction. The aim of our study is to evaluate the overall effects of
      PDE-5 inhibitor administration on splanchnic, pulmonary and systemic hemodynamics
      in cirrhotic patients. METHODS: Sildenafil, a specific PDE-5 inhibitor, was
      administrated orally to cirrhotic patients (n = 7) to see the hemodynamic
      changes. A control group receiving a placebo was used as a point of comparison (n
      = 6). RESULTS: Compared to the control group, the hepatic vein NO and cGMP levels
      were significantly increased after sildenafil administration in the sildenafil
      group (NO from 112.3 +/- 43.5 to 325.3 +/- 117.5 nM, P = 0.018; cGMP from 7.3 +/-
      0.4 to 19.2 +/- 4.2 pmol, P = 0.018). The hepatic venous pressure gradient in the
      sildenafil group did not differ from that of the control group. However, a
      significantly decreased hepatic sinusoidal resistance in the sildenafil group
      (1999 +/- 1243 vs. 1563 +/- 1014 dyne/s/cm(-5), P < 0.05) was noted. The study
      also found that the right arterial pressure, mean pulmonary arterial pressure and
      pulmonary capillary wedge pressure were reduced at 60 min after administration,
      compared with the basal parameters in cirrhotic patients receiving sildenafil
      (RAP1.3 +/- 2.0 vs -0.6 +/- 1.3 mmHg, MPAP 14.1 +/- 11.3 vs 11.7 +/- 9.5 mmHg,
      PCWP 4.6 +/- 1.7 vs 2.9 +/- 1.6 mmHg, P < 0.05 respectively). CONCLUSIONS: An
      oral administration of 50 mg of sildenafil significantly decreased the mean
      pulmonary arterial pressure and hepatic sinusoid resistance with a significant
      increase in hepatic NO and cGMP production, and did not worsen portal
      hypertension in cirrhotic patients.

PMID- 18631255
TI  - Switching from twice-daily abacavir and lamivudine to the once-daily fixed-dose
      combination tablet of abacavir and lamivudine improves patient adherence and
      satisfaction with therapy.
AB  - BACKGROUND: Patients prefer fewer pills and once-daily (qd) dosing without food
      restrictions. We assessed the impact on adherence [by Medication Event Monitoring
      System (MEMS) cap monitoring] of switching from abacavir (ABC) and lamivudine
      (3TC) twice daily (bid) to ABC/3TC fixed-dose formulation (FDC, Kivexa) qd to
      achieve a qd regimen. METHODS: A randomized, open-label, 8-week study comparing
      adherence, efficacy and safety of immediate vs. delayed switching from ABC/3TC to
      FDC qd. RESULTS: Ninety-four patients were dosed. Significantly improved
      adherence was observed at week 4 with qd ABC/3TC across all three adherence
      variables: taking compliance 99.2% (90.7-100%) vs. 96.6% (60.0-100%) (P=0.017);
      dosing compliance 97.1% (64.3-100%) vs. 91.9% (33.3-100%) (P=0.016); and timing
      compliance 95.5% (53.8-100%) vs. 86.3% (4.3-100%) (P=0.006). Treatment
      satisfaction increased significantly at week 4 with ABC/3TC qd [92% (82-99%) vs.
      85% (75-93%) (P=0.004)]. Two patients were withdrawn from the study because of
      intolerance to ABC/3TC. CONCLUSIONS: Switching from ABC and 3TC bid to ABC/3TC
      FDC qd significantly improved adherence by MEMS cap monitoring at week 4 and
      improved patient satisfaction with therapy. The results remain to be confirmed
      over a longer follow-up. Use of qd regimens supports adherence and improves
      treatment satisfaction relative to bid regimens.

PMID- 18631256
TI  - The relationship between ApoE, TNFA, IL1a, IL1b and IL12b genes and HIV-1
      associated dementia.
AB  - OBJECTIVES: Host genetic factors implicated in AIDS dementia complex (ADC) were
      studied. METHODS: DNA from ADC patients (n=56), unselected HIV-seropositive
      patients (n=112, 171, 185 and 204) and HIV-seronegative controls (n=204, 60, 60,
      96 and 624) were typed for polymorphic loci in genes encoding tumour necrosis
      factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-12 and Apolipoprotein E
      (ApoE). Diagnosis of ADC was based on neurological symptoms, signs and
      neuroimaging findings with other causes of dementia excluded. Patients selected
      had ADC stage > or =1 and CD4 counts of <500 cells/microL. RESULTS: Allele 2 of
      TNFA-308 was more common in ADC patients compared to HIV-positive or HIV-negative
      controls (P=0.005, 0.024). No other differences between ADC patients and control
      groups were significant. Meta-analyses confirmed these results. CONCLUSIONS: This
      study suggests that TNFA-308 allele 2 or an allele in linkage disequilibrium with
      this locus influences ADC.

PMID- 18631257
TI  - Prediction of phenotypic susceptibility to antiretroviral drugs using
      physiochemical properties of the primary enzymatic structure combined with
      artificial neural networks.
AB  - OBJECTIVES: Genotypic interpretation systems extrapolate observed associations in
      datasets to predict viral susceptibility to antiretroviral drugs (ARVs) for given
      isolates. We aimed to develop and validate an approach using artificial neural
      networks (ANNs) that employ descriptors of physiochemical properties for
      mutations in HIV-1 protease (PR) and reverse transcriptase (RT) to predict
      phenotypic susceptibility to all currently approved ARVs. METHOD: We extracted
      pairs of PR and RT gene sequences (n=1507; 98.5% sub-type B) and their
      corresponding exact phenotype values (PhenoSense only, n=10 132) from the
      Stanford HIV database. All amino acid positions and mixture codes were accounted
      for. For each ARV, an ANN was trained with 10-fold internal cross-validation. The
      predictive abilities of these trained ANNs were validated on separate datasets.
      RESULTS: Correlation coefficients between observed and predicted phenotype values
      in the 10-fold cross-validation ranged from: 0.75 (tenofovir) to 0.94 [lamivudine
      (3TC)] for nucleoside RT inhibitors (NRTIs); 0.82 [efavirenz (EFV)] to 0.83
      [nevirapine (NVP)] for non-nucleoside RT inhibitors (NNRTIs); and 0.83
      (atazanavir) to 0.92 (ritonavir) for PR inhibitors (PIs). For the validation set
      the correlation coefficients ranged from 0.76 (didanosine) to 0.96 (3TC) for
      NRTIs; 0.68 (EFV) to 0.81 (NVP) for NNRTIs; and 0.88 (amprenavir) to 0.95
      (saquinavir) for PIs. For C sub-type predictions, with ANNs trained on sub-type B
      data, the correlation coefficient was 0.89. CONCLUSIONS: ANNs, based on the
      physiochemical properties of the PR and RT amino-acid sequences, predict
      phenotypic susceptibility to ARVs inhibiting these enzymes to an extent that is
      comparable to routine phenotypic susceptibility testing. These ANNs can also be
      used to predict resistance to C sub-types.

PMID- 18631258
TI  - Potential health risks of complementary alternative medicines in HIV patients.
AB  - OBJECTIVES: To determine the prevalence and purpose of complementary alternative
      medicines (CAMs) use in people receiving treatment for HIV infection. To identify
      and quantify potential health risks of CAM use in this population and to explore
      options for improved pharmacovigilance. METHODS: Cross-sectional questionnaire
      survey of 293 patients receiving antiretroviral (ARV) therapy at three specialist
      HIV out-patient clinics in central London, UK. The use of herbal medicines and
      supplements was explored, and potentially adverse side effects or significant
      drug interactions with conventional therapies were identified. RESULTS: Of the
      293 patients included, 61% (n=179) were taking herbal remedies or supplements and
      35% (n=103) were using physical treatments. Twenty-seven per cent (n=80) used a
      combination of both. Twenty per cent (n=59) potentially compromised their HIV
      management through using CAM therapy. Ten per cent (n=29) were advised to stop
      their CAMs and 15% (n=43) were made aware of potential drug interactions and
      adverse effects and were advised to monitor their care. CONCLUSIONS: There are
      potentially significant health risks posed by the concomitant use of CAMs in
      patients taking ARV therapy. Medical practitioners need to be able to identify
      CAM use in HIV-positive patients and recognize potential health risks. Patients
      should be encouraged to disclose CAM use to their clinicians and other healthcare
      professionals.

PMID- 18631259
TI  - Spatial dynamics of keystone predation.
AB  - 1. I investigated the effects of dispersal on communities of keystone predators
      and prey. I obtained two key results. 2. First, a strong trade-off between
      competitive ability and predator susceptibility allows consumer coexistence over
      a large resource productivity range, but it also lowers the predator-susceptible
      superior competitor's abundance and increases its risk of extinction. Thus,
      unexpectedly, dispersal plays a more important role in coexistence when predator
      mediated coexistence is strong rather than weak. The interplay between the trade
      off, small population sizes resulting from transient oscillations, and dispersal
      leads to qualitatively different species distributions depending on the relative
      mobilities of the consumers and predator. These differences yield comparative
      predictions that can be tested with data on trade-off strength, dispersal rates,
      and species distributions across productivity gradients. 3. Second, there is an
      asymmetry between species in their dispersal effects: the predator-resistant
      inferior competitor's dispersal has a large effect, but the predator-susceptible
      superior competitor's dispersal has no effect, on coexistence and species'
      distributions. The inferior competitor's dispersal also mediates the predator's
      dispersal effects: the predator's dispersal has no effect when the inferior
      competitor is immobile, and a large effect when it is mobile. The net outcome of
      the direct and indirect effects of the inferior competitor's dispersal is a
      qualitative change in the species' distributions from interspecific segregation
      to interspecific aggregation. 4. The important point is that differences between
      species in how they balance resource acquisition and predator avoidance can lead
      to unexpected differences in their dispersal effects. While consumer coexistence
      in the absence of dispersal is driven largely by the top predator, consumer
      coexistence in the presence of dispersal is driven largely by the predator
      resistant inferior competitor.

PMID- 18631260
TI  - Maternal effects mediated by maternal age: from life histories to population
      dynamics.
AB  - 1. Maternal effects describe how mothers influence offspring life histories. In
      many taxa, maternal effects arise by differential resource allocation to young,
      often identified by variation in propagule size, and which affects individual
      traits and population dynamics. 2. Using a laboratory model system, the soil mite
      Sancassania berlesei, we show that, controlling for egg size, older mothers lay
      eggs that hatch later, develop more slowly, and mature at larger body sizes. 3.
      Such differences in life histories lead to marked population dynamical effects
      lasting for multiple generations, as evidenced by an experiment initiated with
      similarly sized eggs that came from young or old mothers. Differences in
      maturation from the initial cohort led to differences in population structure and
      life history that propagated the initial differences over time. 4. Maternal-age
      effects, which are not related to gross provisioning of the egg and are therefore
      phenotypically cryptic, can have profound implications for population dynamics,
      especially if environmental variation can affect the age structure of the adult
      population.

PMID- 18631261
TI  - Geographical gradients in the population dynamics of North American prairie
      ducks.
AB  - 1. Geographic gradients in population dynamics may occur because of spatial
      variation in resources that affect the deterministic components of the dynamics
      (i.e. carrying capacity, the specific growth rate at small densities or the
      strength of density regulation) or because of spatial variation in the effects of
      environmental stochasticity. To evaluate these, we used a hierarchical Bayesian
      approach to estimate parameters characterizing deterministic components and
      stochastic influences on population dynamics of eight species of ducks (mallard,
      northern pintail, blue-winged teal, gadwall, northern shoveler, American wigeon,
      canvasback and redhead (Anas platyrhynchos, A. acuta, A. discors, A. strepera, A.
      clypeata, A. americana, Aythya valisineria and Ay. americana, respectively)
      breeding in the North American prairies, and then tested whether these parameters
      varied latitudinally. 2. We also examined the influence of temporal variation in
      the availability of wetlands, spring temperature and winter precipitation on
      population dynamics to determine whether geographical gradients in population
      dynamics were related to large-scale variation in environmental effects.
      Population variability, as measured by the variance of the population
      fluctuations around the carrying capacity K, decreased with latitude for all
      species except canvasback. This decrease in population variability was caused by
      a combination of latitudinal gradients in the strength of density dependence,
      carrying capacity and process variance, for which details varied by species. 3.
      The effects of environmental covariates on population dynamics also varied
      latitudinally, particularly for mallard, northern pintail and northern shoveler.
      However, the proportion of the process variance explained by environmental
      covariates, with the exception of mallard, tended to be small. 4. Thus,
      geographical gradients in population dynamics of prairie ducks resulted from
      latitudinal gradients in both deterministic and stochastic components, and were
      likely influenced by spatial differences in the distribution of wetland types and
      shapes, agricultural practices and dispersal processes. 5. These results suggest
      that future management of these species could be improved by implementing harvest
      models that account explicitly for spatial variation in density effects and
      environmental stochasticity on population abundance.

PMID- 18631262
TI  - Development and evaluation of a one-step loop-mediated isothermal amplification
      for detection of spring viraemia of carp virus.
AB  - AIM: Spring viraemia of carp virus (SVCV) is the causative agent of SVC disease.
      The main aim of our study was to develop a one-step reverse transcription loop
      mediated isothermal amplification (RT-LAMP) assay for rapid, sensitive and
      effective detection of SVCV. METHODS AND RESULTS: A set of four specific primers,
      two outer and two inner primers were designed based on the SVCV M gene for RT
      LAMP assay. The sensitivity and specificity of RT-LAMP were determined and
      clinical test was performed under optimized amplification conditions (64 degrees
      C, 60 min). The results showed that the assay has a high specificity and the
      detection limit was 80 copies using 10-fold series dilutions of SVCV RNA, 10
      times more sensitive than nest reverse transcription-polymerase chain reaction.
      In the detection of 472 fish samples, this assay showed excellent agreement with
      the standard virus isolation method (kappa = 0.807). CONCLUSIONS: A sensitive and
      specific RT-LAMP assay was successfully developed to monitor and detect SVCV.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides a robust method for
      evaluating the risk of SVCV. Given the advantages of LAMP in the detection of
      SVCV, this method can be applied to diagnose other viruses, which pose serious
      threats to the aquaculture industry.

PMID- 18631264
TI  - Endocardial transcatheter stimulation of the AV nodal fat pad: stabilization of
      rapid ventricular rate response during atrial fibrillation in left ventricular
      failure.
AB  - INTRODUCTION: Recent acute studies demonstrated that atrioventricular (AV) node
      vagal stimulation during atrial fibrillation (AF) decreases the mean ventricular
      rate, thus improving hemodynamics. METHODS AND RESULTS: We report a case of a
      woman with acute heart failure (HF), chronic AF with untreatable ventricular
      rapid response, in severe hypotensive state due to a cardiogenic shock. The
      patient underwent left ventricular (LV) pacemaker implantation and received 50 Hz
      AV node stimulation, delivered through a posteroseptal atrial lead, thus allowing
      a 100% pacing. Hemodynamics improvements allowed carvedilol titration; the rate
      was below 85 bpm after 4 days, then the atrial lead was removed. CONCLUSIONS:
      This novel strategy may allow controlling the rapid AV response in patients
      undergoing pacemaker implantation.

PMID- 18631265
TI  - Newly diagnosed arrhythmogenic right ventricular dysplasia in an octogenarian.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is thought to
      be a disease of the young, with the majority of newly diagnosed patients under 40
      years of age. Establishing this diagnosis in elderly patients may be challenging,
      and a few reports exist of patients older than 70 years diagnosed with ARVD/C at
      autopsy. We report the case of an octogenarian with antemortem newly diagnosed
      ARVD/C. This case report represents the oldest patient to date to have a newly
      established diagnosis of ARVD/C and highlights the difficulty in making the
      diagnosis in the elderly.

PMID- 18631267
TI  - Getting the most out of life.

PMID- 18631268
TI  - Atrial fibrillation after atrial flutter ablation: is atrial fibrillation the
      primary arrhythmia?

PMID- 18631269
TI  - His delay: a case of ice on the path?

PMID- 18631270
TI  - Differences in 12-lead electrocardiogram between symptomatic and asymptomatic
      Brugada syndrome patients.

PMID- 18631271
TI  - Ventricular fibrillation induced by a narrow QRS complex tachycardia in a patient
      with Brugada syndrome.

PMID- 18631272
TI  - Mortality of heart failure patients after cardiac resynchronization therapy:
      identification of predictors.
AB  - INTRODUCTION: A direct comparison of survival benefits between cardiac
      resynchronization therapy-pacemaker (CRT-P) and defibrillator (CRT-D) was not yet
      performed, leaving clinicians to question whether CRT-P alone is enough to
      protect congestive heart failure (CHF) patients from sudden cardiac death and
      whether CRT-D should be implanted to all CHF patients indicated for biventricular
      pacing. This study attempts to make this type of comparison in a large CHF
      population and seeks to identify predictors of death in patients with different
      comorbidities. METHODS AND RESULTS: Study population consisted of 542 consecutive
      patients who were implanted with either CRT-P (N = 147) or CRT-D (N = 395)
      between 1999 and 2005. Patients' clinical and follow-up data were entered in a
      prospective registry and retrieved for analysis. The primary endpoint of this
      study was all-cause mortality during follow-up. Total all-cause mortality was
      significantly lower among patients with CRT-D (18.5% vs. 38.8% of CRT-P, chi(2)=
      25.11, P < 0.001). Patients with one of three comorbidities--chronic renal
      failure (OR = 4.885, P = 0.005), diabetes mellitus (OR = 4.130, P = 0.003), and
      history of atrial fibrillation (OR = 1.473, P = 0.036)--appeared to have higher
      risk of death, while treatment with beta-blocker (OR = 0.330, P = 0.002) or CRT-D
      device (OR = 0.334, P = 0.003) seemed to be associated with lower mortality.
      CONCLUSIONS: Data from this nonrandomized study indicate that CRT-D has
      additional survival benefits over CRT-P. Given these findings, CRT-D should be
      recommended to most CHF patients with indications for biventricular pacing. After
      CRT implant, chronic renal failure, diabetes mellitus, and history of atrial
      fibrillation are strong independent predictors of death.

PMID- 18631273
TI  - Upper loop reentry post mitral valve repair.

PMID- 18631274
TI  - Novel measures of heart rate variability predict cardiovascular mortality in
      older adults independent of traditional cardiovascular risk factors: the
      Cardiovascular Health Study (CHS).
AB  - Novel HRV Predicts CV Mortality in the Elderly. BACKGROUND: It is unknown whether
      abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart
      rate variability identify older adults at increased risk of cardiovascular death
      (CVdth). METHODS: Data from 1,172 community-dwelling adults, ages 72 +/- 5 (65
      93) years, who participated in the Cardiovascular Health Study (CHS), a study of
      risk factors for CV disease in people >or=65 years. HRT and the short-term
      fractal scaling exponent (DFA1) derived from 24-hour Holter recordings. HRT
      categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal)
      or abnormal (TS and/or TO abnormal). DFA1 categorized as low (<or=1) or high
      (>1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata
      (low = <10, mid = 10-20, and high >20) and adjusted for prevalent clinical
      cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature
      beat counts (VPCs). RESULTS: CVdths (N = 172) occurred over a median follow-up of
      12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of
      CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum
      participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest
      quartile predicted CVdth, but only in the high FRS group. Clinical CV disease
      predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high).
      Diabetes predicted CVdth in the highest FRS group only (RR = 2.2). CONCLUSIONS:
      The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth
      among older adults even after adjustment for conventional CVD risk measures and
      the presence of CVD.

PMID- 18631275
TI  - Mapping of intraatrial reentrant tachycardias by remote magnetic navigation in
      patients with d-transposition of the great arteries after mustard or senning
      procedure.
AB  - Remote Magnetic Mapping After Mustard/Senning Procedure. INTRODUCTION: Mapping of
      intraatrial reentrant tachycardia (IART) still presents a challenge in complex
      congenital heart disease. The goal of this work was to present our initial
      experience with remote magnetic navigation (RMN) for mapping of IART in four
      patients after the atrial switch procedure (Mustard n = 1, Senning n = 3) for d
      transposition of the great arteries. METHODS: Three-dimensional (3D) mapping of
      the systemic venous atrium and the pulmonary venous atrium (PVA) was performed
      using RMN (Niobe) in conjunction with 3D mapping (CartoRMT). The maps were fused
      with a CT-based 3D anatomy. RESULTS: All patients had cavotricuspid isthmus
      dependent IART with a mean atrial cycle length of 305 ms. Mapping of both atria
      (PVA retrogradely by passing the aortic and tricuspid valve) was feasible and
      safe. The procedure time for IART mapping ranged from 210 to 320 minutes with a
      mean of 251 minutes. The fluoroscopy time for IART mapping ranged from 15.8 to
      45.0 minutes (mean 31.6 minutes) for patients, and ranged from 12.3 to 24.3
      minutes with a mean of 19.5 minutes for physicians. No procedural complications
      occurred. CONCLUSION: Precise mapping of IART in the complex anatomical
      structures after an atrial switch procedure was feasible and safe using RMN. The
      maneuverability of the catheter was possible even with a retrograde access
      crossing two valves. Further reduction of procedural and fluoroscopy times for
      both patients and physicians seems possible.

PMID- 18631276
TI  - Control of head lice with a coconut-derived emulsion shampoo.
AB  - OBJECTIVE: To evaluate a novel coconut-derived emulsion (CDE) shampoo against
      head lice infestation in children. DESIGN: A school trial in which pupils were
      treated on days 0 and 7 and checked on days 8 and 15 and a family trial where
      product was applied by parents three times in 2 weeks or used as a cosmetic
      shampoo and checked on days 14 and days 70. SETTING: UK schools in Bristol and
      Western-super-Mare and families in Northern Somerset. MAIN OUTCOME MEASURE:
      Numbers of children free from infestation after treatment. RESULTS: In the school
      trial, percentage cures at day 8 were 14% (permethrin, n=7) and 61% (CDE, n=37).
      In the family trial where all family members were treated, cure rate was 96%
      (n=28), and if the shampoo was subsequently used as a cosmetic shampoo, only 1 of
      12 children became re-infested after 10 weeks. CONCLUSION: CDE shampoo is a novel
      effective method of controlling head lice and used after treatment as a cosmetic
      shampoo can aid in the reduction of re-infestation.

PMID- 18631277
TI  - Pruritus is a common and significant symptom of acne.
AB  - BACKGROUND: Acne is a common condition in both adolescents and adults.
      Characteristics of acne are well described, but itch is rarely mentioned as a
      clinical feature. Pruritus could be a significant contributory factor to the
      burden of disability in patients with acne. OBJECTIVE: We examine the prevalence
      of pruritus and its clinical attributes in patients with acne in an outpatient
      clinic. STUDY DESIGN: Descriptive study over a 15 month period from October 2005
      to December 2006. PATIENTS AND METHODS: 120 consecutive patients with acne
      attending an outpatient clinic at National Skin Centre, Singapore were recruited.
      Pruritus was evaluated using a validated questionnaire. Severity of acne was
      determined using FDA Global Acne Grading. RESULTS: 84 patients (70%) reported
      itch in acne. Patients who experienced itch in acne tended to be slightly older
      (p = 0.05). Majority of patients (83%) reported itch at noon and most experienced
      itch on a transient nature. The most common descriptor of itch was tickling
      (68%). Severity of pruritus in acne was comparable to mosquito-bite and it
      significantly affected patients' mood (55%). Common aggravating factors for the
      pruritus were sweat (71%), heat (62%) and stress (31%). A significant proportion
      of patients with itch (52%) had scratched or rubbed the affected area while 37%
      would wash the area to find relief. CONCLUSION: Our results suggest that itch is
      a common and significant symptom in acne. Acne patients experienced considerable
      disability due to the associated pruritus.

PMID- 18631278
TI  - Exaggerated onychodermal band: physiologic, triggered by nail plate infection,
      drug-induced or idiopathic?

PMID- 18631279
TI  - Eccrine naevus with clear cell syringoma.

PMID- 18631280
TI  - Condition dependence of sexually dimorphic colouration and longevity in the
      ambush bug Phymata americana.
AB  - Sexually selected traits that are costly are predicted to be more condition
      dependent than nonsexually selected traits. Assuming resource limitation,
      increased allocation to a sexually selected trait may also come at a cost to
      other fitness components. To test these predictions, we varied adult food ration
      to manipulate condition in the colour dimorphic bug, Phymata americana. We
      compared the degree of condition dependence in a sexually selected trait
      expressed in males to a nonsexually selected trait expressed in males and
      females. We also evaluated the effects of condition on longevity of both sexes.
      We found that the expression of these colour pattern traits was strongly
      influenced by both diet and age. As expected, the strength of condition
      dependence was much more pronounced in the sexually selected, male-limited trait
      but the nonsexual trait also exhibited significant condition dependence in both
      sexes. The sexually selected male trait also exhibited a higher coefficient of
      phenotypic variation than the nonsexually selected trait in males and females.
      Diet had contrasting effects on male and female longevity; increased food
      availability had positive effects on female lifespan but these effects were not
      detected in males, suggesting that males allocated limited resources
      preferentially to sexually selected traits. These results are consistent with the
      expectation that optimal allocation to various fitness components differs between
      the sexes.

PMID- 18631281
TI  - Chemical fingerprinting of adhesive tapes by GCMS detection of petroleum
      hydrocarbon products.
AB  - Pressure-sensitive adhesive tapes often represent key evidence of crimes such as
      assault, rape or homicide; thus, the development of analytical techniques able to
      contribute to a detailed characterization of these materials is of forensic
      importance. The gas chromatography-mass spectrometry (GCMS) analysis of the
      solvent extractable fractions of a suite of electrical and gaffer adhesive tapes
      spanning a range of colors and manufacturers identified a number of petroleum
      derived hydrocarbons. Molecular and isotopic analyses of hydrocarbon constituents
      of complex materials have found wide analytical utility including the forensic
      investigation of oil spills and arson. Here, we investigate the utility of these
      techniques for characterizing the hydrocarbon composition of pressure-sensitive
      adhesive tapes for forensic correlation purposes. Subtle distinction of tape
      samples was evident in the GCMS distribution of several hydrocarbon groups
      including alkyl-naphthalenes, hopane and sterane biomarkers. Linear discriminant
      analysis of the abundances of these products provided high level differentiation
      of tape manufacturer. The distinction of different adhesive tape samples was
      further extended by measurement of their stable carbon isotopic values. The
      molecular and isotopic differences of the petroleum content of tapes are
      consistent with the use of different petroleum materials used in the
      manufacturing process and demonstrate the benefits of the combined use of
      complementary oil hydrocarbon characterization approaches. This study reveals the
      forensic potential of using established petroleum characterization methods for
      characterizing materials with a petroleum-derived hydrocarbon element.

PMID- 18631282
TI  - Substitution of human for horse urine disproves an accusation of doping*.
AB  - In order to detect switching and/or manipulation of samples, the owner of a
      stallion asked our lab to perform a DNA test on a positive doping urine sample.
      The objective was to compare the urine DNA profile versus blood and hair DNA
      profiles from the same stallion. At first, 10 microsatellite markers were
      investigated to determine the horse identity. No results were obtained when horse
      specific markers were typed in the urine sample. In order to confirm the species
      origin of this sample we analyzed the mitochondrial cytochrome b gene. This
      analysis from blood and hair samples produced reproducible and clear PCR-RFLP
      patterns and DNA sequence match with those expected for horse, while the urine
      sample results were coincident with human. These results allowed us to exclude
      the urine sample from the questioned stallion and determine its human species
      origin, confirming the manipulation of urine sample.

PMID- 18631283
TI  - Food and nutrient intakes of primary school children: a comparison of school
      meals and packed lunches.
AB  - BACKGROUND: New school meal standards are currently being phased in by the
      government in an attempt to improve the nutritional composition of school food.
      However, no standards are applied to packed lunches. The present study aimed to
      compare the food and nutrient intakes of primary school children eating a school
      meal with those taking a packed lunch. METHODS: A sample of 120 children, aged 6
      11 years, was observed once at a lunch time and all items consumed were recorded.
      Nutrient analysis was performed, and differences in nutrient intake between those
      children consuming packed lunches and school meals were determined. RESULTS: Mean
      energy and protein intakes were similar. The amount of energy provided by starchy
      carbohydrate was also similar but, compared with school meals, packed lunches
      provided twice as much energy from sugar (P < 0.001). School meals on average
      provided more energy from fat (P < 0.001), but intakes of saturated fat were
      lower in the school meals group (P = 0.021). Packed lunches provided more sodium
      (P < 0.001), calcium (P < 0.001) and iron (P = 0.016) than the school meals. Very
      few packed lunches contained vegetables, and fruit intake was particularly low
      for those having a school meal. CONCLUSIONS: Children taking a packed lunch to
      school were consuming approximately double the amount of sugar and 50% more
      sodium and saturated fat in their midday meal compared with those having a school
      lunch. However packed lunches were providing children with more calcium, iron and
      fruit.

PMID- 18631284
TI  - Diet and physical activity in patients with colorectal adenomas: directions for
      intervention programmes.
AB  - BACKGROUND: Screening programmes provide an opportunity to combine early
      detection programmes with prevention strategies for chronic disease risk
      reduction. The aim of the current exploratory research was to identify diet and
      activity habits in adults diagnosed with colorectal adenomas on screening
      colonoscopy in order to inform the development of an intervention study in this
      patient group. METHODS: Participants were recruited from colonoscopy clinics and
      completed a 7-day food diary and physical activity record. RESULTS: Valid food
      diaries were completed by 32 participants. Mean daily intake of nonstarch
      polysaccharide was estimated at 14.2 (SD 4.2) g per day and fruit and vegetable
      intake (FVI) at 3.6 (SD 1.9) portions. The highest quartile of FVI consumers
      reported greater consumption of fruit (on any occasion) and vegetables (at
      evening meal) compared with low FVI consumers. Physical activity records (n = 36)
      indicated that walking was the most common method of activity with few
      indications of leisure time sport. Overall, 37% of participants failed to meet
      minimum recommend activity levels. CONCLUSION: The magnitudes of change in
      activity and diet required to conform with current guidelines were estimated.
      Food habits that were pertinent to the population were identified and help to
      provide goal-based guidance for intervention design.

PMID- 18631285
TI  - Exploring dietitians' verbal and nonverbal communication skills for effective
      dietitian-patient communication.
AB  - BACKGROUND: Little is known about how dietitians conduct their communication with
      individual patients in the process of nutrition education. To study this issue,
      both practitioners' and patients' perceptions of dietitians' skills were examined
      in the first phase of a two-phase study. The resulting narratives were used to
      develop a questionnaire to survey Australian dietitians involved in clinical
      practice. METHODS: A purposive sample of dietitians in one state (n = 46; 12%),
      working in hospital, community or private practice, and a quota of their adult
      patients (n = 34), were interviewed. In the second stage, Australian dietitians
      (n = 258; 16%) responded to a national survey in 2006, which asked about
      educational strategies, communication skills, and professional attributes.
      Descriptive statistics were used to compare response distributions, and
      nonparametric statistics were used to examine between-group relationships.
      Criterion for item acceptance was established as >or=70% agreement. Triangulation
      of results revealed strong agreement between data sources. RESULTS: Four main
      communication competencies were established: interpersonal communication skill,
      nonverbal communication, professional values, and counselling skill. There was no
      significant difference in practice by work category or experience. The
      communication competencies, together with 26 accompanying skills, are described.
      CONCLUSION: An understanding of this guide to communication practice might help
      enhance dietitian-patient relations.

PMID- 18631286
TI  - Glycosaminoglycans in the pericellular matrix of chondrons and chondrocytes.
AB  - This is the first study to quantitate and profile the glycosaminoglycan (GAG)
      composition of the pericellular matrix (PCM) of chondrons and chondrocytes using
      the highly sensitive technique; fluorophore-assisted carbohydrate electrophoresis
      (FACE). Bovine articular chondrocytes and chondrons were isolated enzymatically.
      High cell yield and viability were obtained for both preparations. Chondrons had
      strong immunofluorescent labeling for keratan sulphate and chondroitin-6 sulphate
      but no labeling for hyaluronan. We compared the immunofluorescent data with FACE.
      The quantities of total keratan sulphate were determined to be 0.013 +/- 0.002 pg
      cell(-1) and 0.032 +/- 0.003 pg cell(-1) in the chondrocyte and chondron
      preparations, respectively. Four internal keratan sulphate sugars were detected
      (gal beta 1,4glcNAc6S, gal6S beta 1,4glcNAc6S, glcNAc beta 1,3gal and glcNAc6S
      beta 1,3gal) for both preparations but they were present at significantly higher
      concentrations in chondron preparations (P < 0.01). Total chondroitin sulphate
      (CS) was determined to be 0.054 +/- 0.004 pg cell(-1) and 0.077 +/- 0.005 pg
      cell(-1) for chondrocyte and chondron preparations, respectively. Unsulphated CS
      disaccharide levels were similar but chondrons had significantly more chondroitin
      4 sulphated disaccharides and chondroitin-6 sulphated disaccharides (P < 0.05).
      Hyaluronan acid was present at low concentrations (0.010 +/- 0.001 pg cell(-1))
      in both chondrocytes and chondrons. In this study, enzyme digestion coupled with
      FACE separation revealed new information about the differences in GAGs from
      isolated chondrocyte and chondron preparations. Further investigation of the
      differences in GAGs from chondrocytes and chondrons from different zones of
      articular cartilage may be useful for tissue engineering approaches.

PMID- 18631288
TI  - Space radiation-induced inhibition of neurogenesis in the hippocampal dentate
      gyrus and memory impairment in mice: ameliorative potential of the melatonin
      metabolite, AFMK.
AB  - Evaluation of potential health effects from high energy charged particle
      radiation exposure during long duration space travel is important for the future
      of manned missions. Cognitive health of an organism is considered to be
      maintained by the capacity of hippocampal precursors to proliferate and
      differentiate. Environmental stressors including irradiation have been shown to
      inhibit neurogenesis and are associated with the onset of cognitive impairments.
      The present study reports on the protective effects of N(1)-acetyl-N(2)-formyl-5
      methoxykynuramine (AFMK), a melatonin metabolite, against high energy charged
      particle radiation-induced oxidative damage to the brain. We observed that
      radiation exposure (2.0 Gy of 500 MeV/nucleon (56)Fe beams, a ground-based model
      of space radiation) impaired the spatial memory of mice at later intervals
      without affecting the motor activities. AFMK pretreatment significantly
      ameliorated these neurobehavioral ailments. Radiation-induced changes in the
      population of immature and proliferating neurons in the dentate gyrus were
      localized using anti-doublecortin (Dcx) and anti-Ki-67 expression. AFMK
      pretreatment significantly inhibited the loss of Dcx and Ki-67 positive cells.
      Moreover, AFMK pretreatment ameliorated the radiation-induced augmentation of
      protein carbonyls and 4-hydroxyalkenal + malondialdehyde (MDA + HAE) in the brain
      and maintained the total antioxidant capacity of plasma and nonprotein sulfhydryl
      contents in brain.

PMID- 18631289
TI  - Microgenomic analysis reveals cell type-specific gene  expression patterns
      between ray and fusiform initials  within the cambial meristem of Populus.
AB  - The vascular cambium is the meristem in trees that produce wood. This meristem
      consists of two types of neighbouring initials: fusiform cambial cells (FCCs),
      which give rise to the axial cell system (i.e. fibres and vessel elements), and
      ray cambial cells (RCCs), which give rise to rays. There is little molecular
      information on the mechanisms whereby the differing characteristics of these
      neighbouring cells are maintained. A microgenomic approach was adopted in which
      the transcriptomes of FCCs and RCCs dissected out from the cambial meristem of
      poplar (Populus trichocarpa x Populus deltoides var. Boelare) were analysed, and
      a transcriptional database for these two cell types established. Photosynthesis
      genes were overrepresented in RCCs, providing molecular support for the presence
      of photosynthetic systems in rays. Genes that putatively encode transporters
      (vesicle, lipid and metal ion transporters and aquaporins) in RCCs were also
      identified. In addition, many cell wall-related genes showed cell type-specific
      expression patterns. Notably, genes involved in pectin metabolism and xyloglucan
      metabolism were overrepresented in RCCs and FCCs, respectively. The results
      demonstrate the use of microgenomics to reveal differences in biological
      processes in neighbouring meristematic cells, and to identify key genes involved
      in these processes.

PMID- 18631290
TI  - Height-related trends in leaf xylem anatomy and shoot  hydraulic characteristics
      in a tall conifer: safety versus  efficiency in water transport.
AB  - Hydraulic vulnerability of Douglas-fir (Pseudotsuga menziesii) branchlets
      decreases with height, allowing shoots at greater height to maintain hydraulic
      conductance (K shoot) at more negative leaf water potentials (Psi l). To
      determine the basis for this trend shoot hydraulic and tracheid anatomical
      properties of foliage from the tops of Douglas-fir trees were analysed along a
      height gradient from 5 to 55 m. Values of Psi l at which K shoot was
      substantially reduced, declined with height by 0.012 Mpa m(-1). Maximum K shoot
      was reduced by 0.082 mmol m(-2) MPa(-1) s(-1) for every 1 m increase in height.
      Total tracheid lumen area per needle cross-section, hydraulic mean diameter of
      leaf tracheid lumens, total number of tracheids per needle cross-section and leaf
      tracheid length decreased with height by 18.4 microm(2) m(-1), 0.029 microm m(
      1), 0.42 m(-1) and 5.3 microm m(-1), respectively. Tracheid thickness-to-span
      ratio (tw/b)2 increased with height by 1.04 x 10(-3) m(-1) and pit number per
      tracheid decreased with height by 0.07 m(-1). Leaf anatomical adjustments that
      enhanced the ability to cope with vertical gradients of increasing xylem tension
      were attained at the expense of reduced water transport capacity and efficiency,
      possibly contributing to height-related decline in growth of Douglas fir.

PMID- 18631291
TI  - Apoptotic-like programmed cell death  in plants.
AB  - Programmed cell death (PCD) is now accepted as a fundamental cellular process in
      plants. It is involved in defence, development and response to stress, and our
      understanding of these processes would be greatly improved through a greater
      knowledge of the regulation of plant PCD. However, there may be several types of
      PCD that operate in plants, and PCD research findings can be confusing if they
      are not assigned to a specific type of PCD. The various cell-death mechanisms
      need therefore to be carefully described and defined. This review describes one
      of these plant cell death processes, namely the apoptotic-like PCD (AL-PCD). We
      begin by examining the hallmark 'apoptotic-like' features (protoplast
      condensation, DNA degradation) of the cell's destruction that are characteristic
      of AL-PCD, and include examples of AL-PCD during the plant life cycle. The review
      explores the possible cellular 'executioners' (caspase-like molecules;
      mitochondria; de novo protein synthesis) that are responsible for the hallmark
      features of the cellular destruction. Finally, senescence is used as a case study
      to show that a rigorous definition of cell-death processes in plant cells can
      help to resolve arguments that occur in the scientific literature regarding the
      timing and control of plant cell death.

PMID- 18631292
TI  - Different flooding responses in Rorippa amphibia and  Rorippa sylvestris, and
      their modes of expression in F1  hybrids.
AB  - The river floodplain species Rorippa amphibia, Rorippa sylvestris, and their
      hybrid Rorippa x anceps were studied here, with the aim of identifying potential
      species differences with respect to flooding tolerance, and of assessing their
      expression in F1 hybrids. Parents and their F1 hybrids were subjected to three
      flooding treatments mimicking natural conditions, and growth-related and leaf
      morphological traits were compared. In contrast to R. sylvestris, R. amphibia
      responded to waterlogging by forming specialized roots, and its growth was not
      reduced. These traits were dominantly expressed in hybrids. Both species and the
      hybrids established shoot growth over 2 wk of complete submergence. Only in R.
      sylvestris was this not at the expense of root biomass, suggesting that R.
      sylvestris can photosynthesize underwater. Rorippa sylvestris also showed a
      hyponastic response. Hybrids were intermediate to the parents in this respect.
      This study shows that phenotypic expression of parental traits in F1 hybrids is
      mostly additive, but can also be dominant. This suggests that a large overlap in
      habitat use of parents and hybrids is likely. If such an overlap occurs, the main
      evolutionary consequences of hybridization in Rorippa will be the introgression
      of genes, as the hybrids are fully fertile.

PMID- 18631293
TI  - Quantitative trait locus mapping for seed mineral  concentrations in two
      Arabidopsis thaliana recombinant  inbred populations.
AB  - Biofortification of foods, achieved by increasing the concentrations of minerals
      such as iron (Fe) and zinc (Zn), is a goal of plant scientists. Understanding
      genes that influence seed mineral concentration in a model plant such as
      Arabidopsis could help in the development of nutritionally enhanced crop
      cultivars. Quantitative trait locus (QTL) mapping for seed concentrations of
      calcium (Ca), copper (Cu), Fe, potassium (K), magnesium (Mg), manganese (Mn),
      phosphorus (P), sulfur (S), and Zn was performed using two recombinant inbred
      line (RIL) populations, Columbia (Col) x Landsberg erecta (Ler) and Cape Verde
      Islands (Cvi) x Ler, grown on multiple occasions. QTL mapping was also performed
      using data from silique hulls and the ratio of seed:hull mineral concentration of
      the Cvi x Ler population. Over 100 QTLs that affected seed mineral concentration
      were identified. Twenty-nine seed QTLs were found in more than one experiment,
      and several QTLs were found for both seed and hull mineral traits. A number of
      candidate genes affecting seed mineral concentration are discussed. These results
      indicate that A. thaliana is a suitable and convenient model for discovery of
      genes that affect seed mineral concentration. Some strong QTLs had no obvious
      candidate genes, offering the possibility of identifying unknown genes that
      affect mineral uptake and translocation to seeds.

PMID- 18631294
TI  - Long-distance transport of mRNA via parenchyma cells  and phloem across the host
      parasite junction in Cuscuta.
AB  - It has been shown that the parasitic plant dodder (Cuscuta pentagona) establishes
      a continuous vascular system through which water and nutrients are drawn. Along
      with solutes, viruses and proteins, mRNA transcripts are transported from the
      host to the parasite. The path of the transcripts and their stability in the
      parasite have yet to be revealed. To discover the route of mRNA transportation,
      the in situ reverse transcriptase-polymerase chain reaction (RT-PCR) technique
      was used to locally amplify host transcript within parasitic tissue. The
      stability of host mRNA molecules was also checked by monitoring specific
      transcripts along the growing dodder thread. Four mRNAs, alpha and beta subunits
      of PYROPHOSPHATE (PPi)-DEPENDENT PHOSPHOFRUCTOKINASE (LePFP), the small subunit
      of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), and GIBBERELLIC
      ACID INSENSITIVE (LeGAI), were found to move from host (tomato (Solanum
      lycopersicum)) to dodder. LePFP mRNA was localized to the dodder parenchyma cells
      and to the phloem. LePFP transcripts were found in the growing dodder stem up to
      30 cm from the tomato-dodder connection. These results suggest that mRNA
      molecules are transferred from host to parasite via symplastic connections
      between parenchyma cells, move towards the phloem, and are stable for a long
      distance in the parasite. This may allow developmental coordination between the
      parasite and its host.

PMID- 18631295
TI  - Plasticity of maritime pine (Pinus pinaster) wood-forming  tissues during a
      growing season.
AB  - The seasonal effect is the most significant external source of variation
      affecting vascular cambial activity and the development of newly divided cells,
      and hence wood properties. Here, the effect of edapho-climatic conditions on the
      phenotypic and molecular plasticity of differentiating secondary xylem during a
      growing season was investigated. Wood-forming tissues of maritime pine (Pinus
      pinaster) were collected from the beginning to the end of the growing season in
      2003. Data from examination of fibre morphology, Fourier-transform infrared
      spectroscopy (FTIR), analytical pyrolysis, and gas chromatography/mass
      spectrometry (GC/MS) were combined to characterize the samples. Strong variation
      was observed in response to changes in edapho-climatic conditions. A genomic
      approach was used to identify genes differentially expressed during this growing
      season. Out of 3512 studied genes, 19% showed a significant seasonal effect.
      These genes were clustered into five distinct groups, the largest two
      representing genes over-expressed in the early- or late-wood-forming tissues,
      respectively. The other three clusters were characterized by responses to
      specific edapho-climatic conditions. This work provides new insights into the
      plasticity of the molecular machinery involved in wood formation, and reveals
      candidate genes potentially responsible for the phenotypic differences found
      between early- and late-wood.

PMID- 18631296
TI  - Influence of warming on soil water potential controls  seedling mortality in
      perennial but not annual species  in a temperate grassland.
AB  - In a water-limited system, the following hypotheses are proposed: warming will
      increase seedling mortality; elevated atmospheric CO2 will reduce seedling
      mortality by reducing transpiration, thereby increasing soil water availability;
      and longevity (i.e. whether a species is annual or perennial) will affect the
      response of a species to global changes. Here, these three hypotheses are tested
      by assessing the impact of elevated CO2 (550 micromol mol(-1) and warming (+2
      degrees C) on seedling emergence, survivorship and establishment in an Australian
      temperate grassland from autumn 2004 to autumn 2007. Warming impacts on seedling
      survivorship were dependent upon species longevity. Warming reduced seedling
      survivorship of perennials through its effects on soil water potential but the
      seedling survivorship of annuals was reduced to a greater extent than could be
      accounted for by treatment effects on soil water potential. Elevated CO2 did not
      significantly affect seedling survivorship in annuals or perennials. These
      results show that warming will alter recruitment of perennial species by changing
      soil water potential but will reduce recruitment of annual species independent of
      any effects on soil moisture. The results also show that exposure to elevated CO2
      does not make seedlings more resistant to dry soils.

PMID- 18631297
TI  - Strong host preference of ectomycorrhizal fungi in a Tasmanian wet sclerophyll
      forest as revealed by DNA barcoding and taxon-specific primers.
AB  - Ectomycorrhizal (ECM) symbiosis is a widespread plant nutrition strategy in
      Australia, especially in semiarid regions. This study aims to determine the
      diversity, community structure and host preference of ECM fungi in a Tasmanian
      wet sclerophyll forest. Ectomycorrhizal fungi were identified based on
      anatomotyping and rDNA internal transcribed spacer (ITS)-large subunit (LSU)
      sequence analysis using taxon-specific primers. Host tree roots were identified
      based on root morphology and length differences of the chloroplast trnL region. A
      total of 123 species of ECM fungi were recovered from root tips of Eucalyptus
      regnans (Myrtaceae), Pomaderris apetala (Rhamnaceae) and Nothofagus cunninghamii
      (Nothofagaceae). The frequency of two thirds of the most common ECM fungi from
      several lineages was significantly influenced by host species. The lineages of
      Cortinarius, Tomentella-Thelephora, Russula-Lactarius, Clavulina, Descolea and
      Laccaria prevailed in the total community and their species richness and relative
      abundance did not differ by host species. This study demonstrates that strongly
      host-preferring, though not directly specific, ECM fungi may dominate the below
      ground community. Apart from the richness of Descolea, Tulasnella and Helotiales
      and the lack of Suillus-Rhizopogon and Amphinema-Tylospora, the ECM fungal
      diversity and phylogenetic community structure is similar to that in the
      Holarctic realm.

PMID- 18631298
TI  - Attitudes as an expression of knowledge and "political anchoring": the case of
      nuclear power in the United Kingdom.
AB  - Attitudes toward the use of nuclear energy pose fundamental issues in the
      political debate about how to meet future energy needs. Development of new
      nuclear power facilities faces significant opposition both from knowledgeable
      individuals who display an understanding of the risks attached to various forms
      of power generation and those who follow strict politically based ideological
      dogmas. This article employs data from a 2005 Eurobarometer survey of UK citizens
      to examine the influence of both political preferences and knowledge in
      explaining support of nuclear power. Findings reveal that attitudes about nuclear
      power are highly politically motivated while the influence of knowledge about
      radioactive waste is dependent upon beliefs about the consequences of nuclear
      energy use. Perceptions of being informed about radioactive waste and trust in
      sources providing information about radioactive waste management also predict
      attitudes toward nuclear power generation.

PMID- 18631299
TI  - On the relation between trust and fairness in environmental risk management.
AB  - In this study, we empirically examine the relations between trust, fairness, and
      cooperation within two environmental risk management contexts, one in which the
      focal issue is of high personal moral importance and the other in which the focal
      issue is of low moral importance. Using an experimental design embedded in two
      parallel survey questionnaires, one mailed to residents of Washington State, the
      other to German-speaking residents of Switzerland, we either manipulated or
      constructed three factors, issue importance (high/low), procedural fairness
      (fair/unfair), and policy outcome (risk averse/risk accepting). This design
      enabled us to compare the predictions of the standard account of procedural
      fairness, that trust and cooperation are determined by judgments of fairness,
      with the predictions of an alternative account, that trust and cooperation will
      be determined by judgments of procedural fairness only when the issue involved is
      not morally important. Results for the American case showed that under conditions
      of high issue importance, policy outcome affected judged fairness, trust, and
      cooperation. Under conditions of low issue importance, policy outcome had no
      effect on judged fairness or trust but did have a moderate impact on cooperation.
      Analyses also showed that when issue importance was high, procedural fairness had
      no effects. When issue importance was low, procedural fairness had moderate
      effects on judged fairness and trust. Results for the Swiss case replicated the
      main findings for the American case. Together, these results support the
      alternative model of the relation between trust and fairness, suggesting that the
      efficacy of fair procedures is strictly limited.

PMID- 18631300
TI  - Efficiency of even separation of parallel elements with variable contest
      intensity.
AB  - The article considers strategic defense and attack of a system that can be
      separated into parallel elements. The defender distributes its resource between
      separation and protecting the elements from outside attacks. The vulnerability of
      each element is determined by an attacker-defender contest success function,
      which depends on a contest intensity that may increase or decrease through the
      separation process. The article determines criteria of separation efficiency for
      systems without performance redundancy and 1-out-of-N and Q-out-of-N systems with
      performance redundancy. For the systems with performance redundancy the cases of
      expected damage proportional to the probability that the demand is not met, and
      expected damage proportional to the unsupplied demand, are considered.

PMID- 18631301
TI  - Modeling cholinesterase activity for human dietary risk assessment of carbamate
      insecticides.
AB  - This article demonstrates statistical models to quantify the interaction between
      a carbamate insecticide and acetylcholinesterase. Carbamates are a class of
      chemicals that inhibit the activity of acetylcholinesterase in humans, an enzyme
      involved in the regulation of the neurotransmitter acetylcholine. Following
      exposure to a carbamate insecticide, we specifically address (1) if
      acetylcholinesterase activity recovers to its level of preexposure activity; (2)
      the level of inhibition of acetylcholinesterase activity; (3) the recovery time
      of acetylcholinesterase activity to its preexposure level for a typical
      individual; and (4) the upper percentiles of the recovery time of
      acetylcholinesterase activity across individuals. A nonlinear mixed-effects model
      is fitted to data from a repeated measures experiment conducted with human
      volunteers randomly assigned to a control and four dose groups. Repeated
      measurements were taken prior to exposure and at 1, 2, 4, 6, 8, and 21 hours
      after exposure to the carbamate aldicarb. It was found that full recovery did
      occur. Inhibition at 1 hour was estimated with maximum inhibition most likely
      occurring prior to 1-hour postexposure. In addition, recovery was rapid even for
      sensitive individuals. Given this information, the potential effect from exposure
      to a carbamate consumed in the diet during a day can be quantitatively assessed.

PMID- 18631302
TI  - Examining links between sign-out reporting during shift changeovers and patient
      management risks.
AB  - This article reports on a qualitative study that investigated how various risk
      factors associated with the process of sign-out reporting across shifts in
      critical care hospital environments could lead to flawed communication and thus
      to increased risk of poor patient outcomes. The study was performed in two
      critical care hospital units: the pediatric intensive care unit (PICU) and the
      postanesthesia care unit (PACU). We collected data from observations of eight
      nurses and four resident physicians in the PICU and four nurses and four resident
      physicians in the PACU giving sign-out reports during their shift changes. In
      addition, we conducted semi-structured interviews with a separate sample of
      medical providers consisting of nurse managers, attending physicians, nurses, and
      residents from each of these two units. The issues that were addressed in these
      interviews included how various methods of conducting sign-outs and factors such
      as personality and experience could impact the effectiveness of communication
      during sign-out reporting. We also collected data from these medical providers on
      how failures in communication during sign-out reporting could lead to potentially
      adverse patient outcomes. The article concludes with the presentation of a
      modeling framework that demonstrates how the combined influences of risk factors
      can generate a particularly important type of failure mode in communication and
      how interventions can be targeted to serve as barriers to such events. A number
      of recommendations intended for reducing risks associated with the communication
      of sign-out reports are also presented.

PMID- 18631303
TI  - An integrated approach to oversight assessment for emerging technologies.
AB  - Analysis of oversight systems is often conducted from a single disciplinary
      perspective and by using a limited set of criteria for evaluation. In this
      article, we develop an approach that blends risk analysis, social science, public
      administration, legal, public policy, and ethical perspectives to develop a broad
      set of criteria for assessing oversight systems. Multiple methods, including
      historical analysis, expert elicitation, and behavioral consensus, were employed
      to develop multidisciplinary criteria for evaluating oversight of emerging
      technologies. Sixty-six initial criteria were identified from extensive
      literature reviews and input from our Working Group. Criteria were placed in four
      categories reflecting the development, attributes, evolution, and outcomes of
      oversight systems. Expert elicitation, consensus methods, and multidisciplinary
      review of the literature were used to refine a condensed, operative set of
      criteria. Twenty-eight criteria resulted spanning four categories: seven
      development criteria, 15 attribute criteria, five outcome criteria, and one
      evolution criterion. These criteria illuminate how oversight systems develop,
      operate, change, and affect society. We term our approach "integrated oversight
      assessment" and propose its use as a tool for analyzing relationships among
      features, outcomes, and tradeoffs of oversight systems. Comparisons among
      historical case studies of oversight using a consistent set of criteria should
      result in defensible and evidence-supported lessons to guide the development of
      oversight systems for emerging technologies, such as nanotechnology.

PMID- 18631304
TI  - A combined Monte Carlo and possibilistic approach to uncertainty propagation in
      event tree analysis.
AB  - In risk analysis, the treatment of the epistemic uncertainty associated to the
      probability of occurrence of an event is fundamental. Traditionally,
      probabilistic distributions have been used to characterize the epistemic
      uncertainty due to imprecise knowledge of the parameters in risk models. On the
      other hand, it has been argued that in certain instances such uncertainty may be
      best accounted for by fuzzy or possibilistic distributions. This seems the case
      in particular for parameters for which the information available is scarce and of
      qualitative nature. In practice, it is to be expected that a risk model contains
      some parameters affected by uncertainties that may be best represented by
      probability distributions and some other parameters that may be more properly
      described in terms of fuzzy or possibilistic distributions. In this article, a
      hybrid method that jointly propagates probabilistic and possibilistic
      uncertainties is considered and compared with pure probabilistic and pure fuzzy
      methods for uncertainty propagation. The analyses are carried out on a case study
      concerning the uncertainties in the probabilities of occurrence of accident
      sequences in an event tree analysis of a nuclear power plant.

PMID- 18631305
TI  - The application of genetic information for regulatory standard setting under the
      clean air act: a decision-analytic approach.
AB  - In 2002, the U.S. Environmental Protection Agency (EPA) released an "Interim
      Policy on Genomics," stating a commitment to developing guidance on the inclusion
      of genetic information in regulatory decision making. This statement was followed
      in 2004 by a document exploring the potential implications. Genetic information
      can play a key role in understanding and quantifying human susceptibility, an
      essential step in many of the risk assessments used to shape policy. For example,
      the federal Clean Air Act (CAA) requires EPA to set National Ambient Air Quality
      Standards (NAAQS) for criteria pollutants at levels to protect even sensitive
      populations from adverse health effects with an adequate margin of safety.
      Asthmatics are generally regarded as a sensitive population, yet substantial
      research gaps in understanding genetic susceptibility and disease have hindered
      quantitative risk analysis. This case study assesses the potential role of
      genomic information regarding susceptible populations in the NAAQS process for
      fine particulate matter (PM(2.5)) under the CAA. In this initial assessment, we
      model the contribution of a single polymorphism to asthma risk and mortality
      risk; however, multiple polymorphisms and interactions (gene-gene and gene
      environment) are known to play key roles in the disease process. We show that the
      impact of new information about susceptibility on estimates of population risk or
      average risk derived from large epidemiological studies depends on the
      circumstances. We also suggest that analysis of a single polymorphism, or other
      risk factor such as health status, may or may not change estimates of individual
      risk enough to alter a particular regulatory decision, but this depends on
      specific characteristics of the decision and risk information. We also show how
      new information about susceptibility in the context of the NAAQS for PM(2.5)
      could have a large impact on the estimated distribution of individual risk. This
      would occur if a group were consequently identified (based on genetic and/or
      disease status), that accounted for a disproportionate share of observed effects.
      Our results highlight certain conditions under which genetic information is
      likely to have an impact on risk estimates and the balance of costs and benefits
      within groups, and highlight critical research needs. As future studies explore
      more fully the relationship between exposure, genetic makeup, and disease status,
      the opportunity for genetic information and disease status to play pivotal roles
      in regulation can only increase.

PMID- 18631306
TI  - A simulation study of quantitative risk assessment for bivariate continuous
      outcomes.
AB  - The neurotoxic effects of chemical agents are often investigated in controlled
      studies on rodents, with binary and continuous multiple endpoints routinely
      collected. One goal is to conduct quantitative risk assessment to determine safe
      dose levels. Yu and Catalano (2005) describe a method for quantitative risk
      assessment for bivariate continuous outcomes by extending a univariate method of
      percentile regression. The model is likelihood based and allows for separate dose
      response models for each outcome while accounting for the bivariate correlation.
      The approach to benchmark dose (BMD) estimation is analogous to that for quantal
      data without having to specify arbitrary cutoff values. In this article, we
      evaluate the behavior of the BMD relative to background rates, sample size, level
      of bivariate correlation, dose-response trend, and distributional assumptions.
      Using simulations, we explore the effects of these factors on the resulting BMD
      and BMDL distributions. In addition, we illustrate our method with data from a
      neurotoxicity study of parathion exposure in rats.

PMID- 18631307
TI  - Inter-observer variation in paediatric clinical signs between different grades of
      staff examining children admitted to hospital in Tanzania.
AB  - BACKGROUND AND OBJECTIVE: Children are often admitted to district hospitals in
      Africa without an adequate record of clinical examination, a problem that could
      be reduced by greater involvement of nurses in their assessment. We aimed to
      ascertain whether hospital nurses in a district hospital could conduct paediatric
      examinations as reliably as clinical staff, when provided with a short structured
      training session. METHODS: Hospital nurses (HN), hospital clinical officers (HCO)
      and research clinical officers (RCO) repeated examinations on children admitted
      to the paediatric ward shortly after the first examination by an RCO. Kappa
      scores were used to compare the agreement on the presence or absence of basic
      clinical signs by different categories of staff. RESULTS: Among 439 paired
      examinations the agreement between RCOs on clinical signs was slightly higher
      than for HCOs or HNs; the mean (median) Kappa scores for all signs examined were
      0.54 (0.57) for RCO-RCO, 0.49 (0.49) for RCO-HCO and 0.50 (0.49) for RCO-HN.
      Levels of agreement were lower if children were under the age of 18 months or if
      they cried during the examination. CONCLUSIONS: Nurses with basic training appear
      to perform as well as clinically trained staff in eliciting essential signs in
      acutely ill children. Their role in the initial and ongoing assessment of these
      children should be reviewed in light of the critical shortages in clinically
      trained staff in African hospitals.

PMID- 18631308
TI  - After a decade of annual dose mass ivermectin treatment in Cameroon and Uganda,
      onchocerciasis transmission continues.
AB  - OBJECTIVE: To evaluate the effectiveness of 10 years' annual single dose
      ivermectin treatment on onchocerciasis transmission in hyperendemic areas of
      Cameroon and Uganda. METHODS: Baseline nodule and microfilaria ('skin snip')
      prevalence data were available from 10 hyperendemic sentinel communities in
      Cameroon (from 1996) and hyperendemic 20 sentinel communities in Uganda (from
      1993). We returned to these villages in 2005, 10 months after the last annual
      ivermectin distribution, to repeat the cross-sectional surveys. Each sentinel
      community reported a mean interval treatment coverage of eligible persons of >88%
      (range 37-100%). Data were analyzed for more than 6200 person examinations. In
      Cameroon, 719 people >or=10 years were examined at the baseline survey in 1996
      and 838 at the follow-up survey in 2005. In Uganda, 1590 people >or=10 years were
      examined at the baseline survey in 1993 and 2122 people at the follow-up survey
      in 2005. We also examined children under 10 in Cameroon (1996, n = 185; 2005, n =
      448) and Uganda (1993, n = 177; 2005, n = 130). In Uganda, the vitality of worms
      was judged using standard histological criteria in 80 nodules excised in 2005.
      RESULTS: The prevalence of microfilaria carriers among older children and adults
      (>or=10 years) in Cameroon sentinel communities dropped from 70.1% to 7.04% (P <
      0.0001) over the 10-year treatment period; that of nodule carriers from 58% to
      9.55% (P < 0.0001). Similarly, in Uganda, the prevalence of microfilaria carriers
      fell from 71.9% to 7.49% (P < 0.0001) over the 13-year treatment period, and that
      of nodule carriers from 53.21% to 9.66% (P < 0.0001). The number of microfilaria
      carriers among children <10 years in Cameroon decreased from 29.73% to 3.8% (P <
      0.0001), and in Uganda from 33.89% to 3.1% (P < 0.0001). In 2005, worms excised
      from nodules in Uganda, 81.4% of males remained alive, and 64% of females, with
      24% of them inseminated. CONCLUSION: A decade or more of annual single dose
      ivermectin treatment in hyperendemic areas has reduced onchocerciasis to
      'hypoendemicity', but onchocerciasis transmission persists. For now, annual
      treatment with ivermectin should be continued in formerly mesoendemic and
      hyperendemic zones.

PMID- 18631309
TI  - Introduction of Aedes albopictus in Gabon: what consequences for dengue and
      chikungunya transmission?
AB  - The 2007 outbreak of chikungunya in Gabon has indicated the potential of this
      disease to spread beyond its usual range ensuing from the expansion of the
      mosquito Aedes albopictus. A few cases of dengue (DEN) infection were also
      detected. Because little is known about the potential for Gabonese mosquito
      species to transmit both chikungunya and DEN viruses (DENV), we conducted studies
      to determine the susceptibility of Ae. albopictus and Aedes aegypti collected in
      Libreville to both viruses by experimental infections. Disseminated infection
      rates were high for Ae. albopictus infected with chikungunya virus (CHIKV) (66.7
      86%) and low with DENV (13-21.4%). Moreover, Ae. aegypti sp. formosus was a less
      efficient vector of CHIKV than Ae. albopictus. The recent introduction and
      dissemination of chikungunya associated with the invasion of Ae. albopictus in
      Africa illustrates the potential for CHIKV to spread to other parts of the world.

PMID- 18631310
TI  - Envenoming after carpet viper (Echis ocellatus) bite during pregnancy: timely use
      of effective antivenom improves maternal and foetal outcomes.
AB  - The report describes successful management of 10 women in 2nd and 3rd pregnancy
      trimesters with EchiTab IgG antivenom after carpet viper (Echis ocellatus)
      envenoming. All women survived but foetal loss in a victim with delayed
      presentation and a case of mild hypersensitivity reaction were recorded.
      Excellent outcomes can be achieved in rural and semi-nomadic populations without
      specialized care and immediate access and provision of effective antivenoms is
      paramount in curtailing snakebite maternal morbidity, mortality and foetal loss.

PMID- 18631311
TI  - Nested PCRs and sequencing of nuclear ITS-rDNA fragments detect three Leishmania
      species of gerbils in sandflies from Iranian foci of zoonotic cutaneous
      leishmaniasis.
AB  - OBJECTIVE: To identify and understand the natural transmission cycles of
      Leishmania in Iranian sandflies. METHOD: Nested PCR protocols were developed to
      amplify two regions of the ribosomal RNA amplicon of Leishmania (ITS1-5.8S rRNA
      gene, and a microsatellite DNA region of ITS2), which were species-specific by
      DNA sequence or fragment size. RESULTS: The PCR assays detected in Iranian
      sandflies not only Leishmania major but also for the first time L. turanica and
      L. gerbilli sensu lato, two other parasites of the great gerbil. All three
      parasites were found in the northeast and centre of Iran, in two foci of rural
      Zoonotic Cutaneous Leishmaniasis (ZCL) caused by L. major. Fifty infections were
      detected in common sandfly species: at least six geographically differentiated
      haplotypes of L. major in four to five sandfly species; one strain of L. gerbilli
      s.l. in five to six sandfly species and one strain of L. turanica in one sandfly
      species. CONCLUSION: Past conclusions about the transmission cycles of L. major
      in Iran should be treated with caution. Careful molecular eco-epidemiological
      investigations are essential for modelling the roles of different sandfly species
      in maintaining and spreading ZCL foci. Even if non-pathogenic to humans, frequent
      inoculations of L. turanica by sandflies might alter the efficacy of vaccines
      against L. major. Phlebotomus papatasi is probably the key vector in many ZCL
      foci because of its abundance and high infection rates with both L. major and L.
      turanica.

PMID- 18631312
TI  - Pharmacovigilance of antimalarial treatment in Uganda: community perceptions and
      suggestions for reporting adverse events.
AB  - OBJECTIVES: The deployment of new antimalarials in Africa provides an important
      opportunity to develop systems for pharmacovigilance. To inform strategies for
      reporting adverse events in Uganda, we investigated local perceptions and
      experiences with antimalarial treatment, and evaluated existing and potential
      systems for pharmacovigilance. METHODS: Focus group discussions (FGD) were
      conducted with community members and health workers from urban and rural Uganda
      exploring knowledge of fever/malaria, perceptions and expectations of treatment,
      understanding of adverse effects, and experiences with adverse events. Sessions
      were recorded, transcribed into English, and analysed using a coding scheme
      developed from pre-defined topics together with themes emerging from the data.
      RESULTS: Between April and July 2006, we conducted 25 FGDs; 16 with community
      members and nine with health workers. All respondents had extensive experience
      with malaria and its treatment. Community members commonly recognized adverse
      effects of antimalarial therapy. However, events were uncommonly reported, and
      certain events were often interpreted as signs of successful treatment. Community
      members often felt that the costs of reporting or seeking additional care
      outweighed the potential benefits. Health workers were unfamiliar with formal
      pathways for reporting, and were deterred by the additional work of reporting and
      fear of incrimination. Respondents provided suggestions for incentives and
      methods of reporting, emphasizing that pharmacovigilance should ideally encompass
      the public and private sector, and the community. CONCLUSIONS: To be successful,
      pharmacovigilance relying on voluntary reporting will require active
      participation of patients and health workers. Addressing the costs and benefits
      of reporting, and providing sensitization, training and feedback will be
      important.

PMID- 18631313
TI  - The importance of context in malaria diagnosis and treatment decisions - a
      quantitative analysis of observed clinical encounters in Tanzania.
AB  - OBJECTIVE: To gain a better understanding of the decision-making context in the
      diagnosis of malaria in order to inform behaviour change strategies, using
      quantitative methods. METHODS: We observed hospital outpatient and inpatient
      consultations in northeast Tanzania where malaria testing was routinely
      available, recording potential influences on testing and prescribing decisions.
      We analysed the effects of variables at patient, clinical context and clinician
      levels on three key decisions in malaria diagnosis and treatment: decision to
      test for malaria, presumptive treatment and treatment of test-negative patients
      with antimalarials. RESULTS: Observation of 2082 consultations took place during
      120 clinics (different shifts on different days and in different departments)
      with 34 clinicians. Malaria tests were requested for 16.9% of patients. This
      decision was driven primarily by clinical symptoms. Of patients not tested for
      malaria, 36.0% were prescribed antimalarials, this decision being associated with
      both clinical and non-clinical factors. In outpatients fever was a strong
      predictor of presumptive treatment [adjusted odds ratio (AOR): 45.9, 95% CI: 30
      73], in inpatients this was less so (AOR: 2.7, 95% CI: 0.98-7.7). Outpatient
      clinicians who were working alone or who had attended <2 in-service training
      sessions in the past year were more likely to prescribe antimalarials
      presumptively. The decision to prescribe antimalarials without also prescribing
      antibiotic treatment to 22.8% patients who tested negative for malaria was not
      driven by clinical symptoms but was associated with age over 5 years, lower
      patient load and male sex of clinician. CONCLUSIONS: Non-clinical factors are
      important in the overdiagnosis of malaria. Strategies to target antimalarials and
      antibiotics better need to use methods that address the context of clinical
      decision making in addition to the dissemination of conventional clinical
      algorithms.

PMID- 18631314
TI  - The outcomes and outpatient costs of different models of antiretroviral treatment
      delivery in South Africa.
AB  - OBJECTIVE: Estimate the average outpatient cost per patient in care and
      responding to treatment 1 year after initiation of antiretroviral therapy (ART)
      under different models of treatment delivery in South Africa. METHODS: At each
      site, medical records for a sample patients of were reviewed 1 year after ART
      initiation. Each subject was assigned to one outcome category: in care and
      responding (IC); in care but not responding (NR); or no longer in care at study
      site (NIC). Average cost per outcomes category was estimated based on resource
      utilisation. RESULTS: Site 1 was an urban public hospital; Site 2 a programme
      that contracts private general practitioners; Site 3 a rural non-governmental
      (NGO) AIDS clinic; and Site 4 a peri-urban NGO primary care clinic. At month 12,
      IC, NR and NIC rates were 67%, 7% and 26% (Site 1); 52%, 3%, and 45% (Site 2);
      63%, 9% and 28% (Site 3); and 76%, 11%, and 13% (Site 4). The average outpatient
      cost per patient initiated was $756 (Site 1), $896 (Site 2), $932 (Site 3) and
      $1,126 (Site 4). When all costs and all outcomes were taken into account, the
      average cost to produce an IC patient was $1,128 (Site 1), $1,723 (Site 2),
      $1,480 (Site 3), and $1,482 (Site 4). CONCLUSION: If all ART patients remain in
      care and responding, total costs will increase but the average cost to produce an
      IC patient will fall. The cost per ART patient treated varies moderately among
      sites. Cost differences increase markedly when patient outcomes are taken into
      account.

PMID- 18631315
TI  - Hypothermia of newborns is associated with excess mortality in the first 2 months
      of life in Guinea-Bissau, West Africa.
AB  - OBJECTIVE: To examine the long-term effects of neonatal hypothermia (HT) on
      survival. METHODS: Using the longitudinal community and hospital surveillance
      system of the Bandim Health Project, we followed children born between 1997 and
      2002 at the only maternity ward in the city. All children's axillary temperature
      was measured within 12 h of birth. They were followed from birth to 6 months of
      life through regular home visits. RESULTS: We identified 2926 live births in the
      study area and 177 deaths before 6 months of age. Based on mortality risk, we
      defined a temperature below 34.5 degrees C as the cut-off point for HT. Two
      hundred and thirty-eight (8%) children had HT. Controlled for birth weight, HT
      was associated with a nearly fivefold increase in mortality during the first 7
      days of life [mortality ratio (MR) = 4.81 (2.90-8.00)] and with increased
      mortality from 8 to 56 days of life [MR = 2.55 (1.29-5.04)]. CONCLUSION: HT is
      associated with excess mortality beyond the perinatal period up to at least 2
      months of age, especially among low-birth-weight children. Hence, failure to
      comply with the WHO guidelines for care of newborns in low-income countries may
      have long-term consequences for child survival which have not previously been
      assessed. The WHO definition of HT should be based on mortality data.

PMID- 18631316
TI  - Malaria in pregnancy in an area of stable and intense transmission: is it
      asymptomatic?
AB  - OBJECTIVE: To report a study of the signs and symptoms of malarial infection
      during pregnancy in an area of stable and intense transmission. METHODS: As part
      of a clinical trial, to assess the efficacy and safety of four antimalarial drug
      regimens in pregnant women, we collected clinical and laboratory data from 900
      parasitaemic pregnant women and 223 non-parasitaemic pregnant women who attended
      an antenatal clinic at a district hospital in Ghana. Frequencies of signs and
      symptoms were calculated and their association with the level of parasitaemia was
      assessed using multivariate logistic regression. RESULTS: History of fever
      (7.8%vs. 44.4%; P < 0.0001), headache (12.5%vs. 43.9%; P < 0.0001), vomiting (0
      vs. 11.5%; P = 0.01), malaise (1.6%vs. 31.6%; P < 0.0001) dizziness (0%vs. 23%; P
      < 0.0001) and fatigue (0%vs. 22.5%; P < 0.0001) was substantially higher in
      parasitaemic primigravidae than in aparasitaemic primigravid women. Similar
      differences in the distribution of the symptoms and signs were observed between
      parasitaemic and aparasitaemic multigravid women. The proportion of women with
      elevated concentrations of aspartate aminotransferase, alanine aminotransferase
      and total bilirubin and its fractions was also higher in parasitaemic than in non
      parasitaemic women. CONCLUSION: In areas of stable malarial transmission, malaria
      in pregnancy is often symptomatic. Although the symptoms are mostly non-specific,
      careful recording of history may be useful to identify women who need a
      confirmatory test and an effective antimalarial treatment.

PMID- 18631317
TI  - Sensitivity and specificity of an index for the diagnosis of TB meningitis in
      patients in an urban teaching hospital in Malawi.
AB  - Tuberculous (TB) meningitis is difficult to diagnose and has a high mortality
      rate, particularly when presentation is delayed. A diagnostic index developed in
      Vietnam, an area of low-HIV seroprevalence, has been proposed as a means to
      differentiate TB meningitis from acute bacterial meningitis using clinical and
      laboratory features. We applied this index over a 4-month period to adults
      presenting with meningitis to an urban teaching hospital in Malawi, where HIV
      seroprevalence is 70% among medical inpatients. Eighty-five consecutive eligible
      patients were studied. Nine had TB meningitis, 64 bacterial meningitis and 12
      cryptococcal meningitis. The sensitivity of the diagnostic index for predicting
      TB meningitis was 78%, with a specificity of 43%, too low to be used in the
      diagnosis of TB meningitis in this setting. This finding is likely to be
      generalizable to other southern African countries with similarly high-HIV
      seroprevalences.

PMID- 18631318
TI  - Substandard medicines in resource-poor settings: a problem that can no longer be
      ignored.
AB  - The circulation of substandard medicines in the developing world is a serious
      clinical and public health concern. Problems include under or over concentration
      of ingredients, contamination, poor quality ingredients, poor stability and
      inadequate packaging. There are multiple causes. Drugs manufactured for export
      are not regulated to the same standard as those for domestic use, while
      regulatory agencies in the less-developed world are poorly equipped to assess and
      address the problem. A number of recent initiatives have been established to
      address the problem, most notably the WHO pre-qualification programme. However,
      much more action is required. Donors should encourage their partners to include
      more explicit quality requirements in their tender mechanisms, while purchasers
      should insist that producers and distributors supply drugs that comply with
      international quality standards. Governments in rich countries should not
      tolerate the export of substandard pharmaceutical products to poor countries,
      while developing country governments should improve their ability to detect
      substandard medicines.

PMID- 18631319
TI  - Pharmacovigilance through consumer feedback (reporting) in the mass treatment of
      lymphatic filariasis using diethylcarbamazine and albendazole in two districts of
      Sri Lanka.
AB  - OBJECTIVE: To document the types and severity of adverse drug reactions to
      diethylcarbamazine and albendazole in randomly selected urban populations from
      Colombo and rural populations from Gampaha, Sri Lanka. METHODS: Interviewers
      administered a pre-tested questionnaire to elicit information about the type and
      severity of adverse drug reactions experienced by recipients. Seeking medical
      treatment and requiring hospital admission for the adverse drug reactions were
      used as indicators for severity. The sample population was selected using the
      cluster sampling method. RESULTS: Two thousand three hundred and nineteen persons
      aged 10 to 90 years (median 40.0) responded to the questionnaire; 63.9% of them
      had received and ingested the drugs. 12.6% reported that they had experienced
      adverse drug reactions, the proportion being similar in urban and rural areas
      (chi2 = 0.05; p = 0.82). Commonly reported reactions were drowsiness (34.7%),
      headache (23.1%), gastrointestinal symptoms (18.7%) and dizziness or faintness
      (11.9%). However, most symptoms were mild (96.3%) and did not interfere with
      daily activities or require medical attention. 3.2% said that they sought medical
      advice for their symptoms; one person (0.5%) who had severe abdominal pain was
      hospitalized. CONCLUSIONS: Fewer people experienced adverse drug reactions than
      in previous years, possibly due to lower microfilariaemia prevalence after
      several rounds of mass drug administration against filariasis. Community
      awareness of adverse drug reactions is essential for improving compliance and for
      the success of the filariasis elimination programme.

PMID- 18631320
TI  - Some highlights of research on aging with invertebrates, 2008.
AB  - This annual review focuses on invertebrate model organisms, which shed light on
      new mechanisms in aging and provide excellent systems for in-depth analysis. This
      year, the first quantitative estimate of evolutionary conservation of genetic
      effects on lifespan has pointed to the key importance of genes involved in
      protein synthesis, a finding confirmed and extended by experimental work. Work in
      Caenorhabditis elegans and Drosophila has highlighted the importance of phase 2
      detoxification in extension of lifespan by reduced insulin/Igf-like signalling.
      Thorough characterization of systems for dietary restriction in C. elegans is
      starting to show differences in the mechanisms by which these interventions
      extend lifespan and has revealed a requirement for autophagy. The response to
      heat shock in C. elegans turns out to be systemic, and mediated by sensory
      neurons, with potentially interesting implications for the response of lifespan
      to temperature. Work in Escherichia coli and yeast has revealed a role for
      retention of aggregated proteins in the parent in the rejuvenation of offspring
      while, as in C. elegans, removal of the germ line in Drosophila turns out to
      extend lifespan. Aging research has suffered the loss of a great scientific
      leader, Seymour Benzer, and his trail-blazing work on aging and neurodegeneration
      is highlighted.

PMID- 18631322
TI  - Neonatal alcohol-induced region-dependent changes in rat brain neurochemistry
      measured by high-resolution magnetic resonance spectroscopy.
AB  - BACKGROUND: Maternal drinking during pregnancy can lead to a range of deleterious
      outcomes in the developing offspring that have been collectively termed fetal
      alcohol spectrum disorders (FASDs). There is interest and recognized value in
      using non-invasive neuroimaging techniques such as magnetic resonance imaging
      (MRI) and magnetic resonance spectroscopy (MRS) to characterize, respectively,
      structural and biochemical alterations in individuals with FASDs. To date,
      however, results with MRS have been inconsistent regarding the degree and/or
      nature of abnormalities. METHODS: High-resolution magic angle spinning (HR-MAS)
      proton ((1)H) MRS is an ex vivo neuroimaging technique that can acquire spectra
      in small punches of intact tissue, providing clinically relevant neurochemical
      information about discrete brain regions. In this study, HR-MAS (1)H MRS was used
      to examine regional neurochemistry in frontal cortex, striatum, hippocampus, and
      cerebellum of young rats previously exposed to ethanol as neonates. Key
      neurochemicals of interest included N-acetyl-aspartate (NAA), glutamate, GABA,
      glutamine, creatine, choline and myo-inositol. RESULTS: Daily neonatal alcohol
      exposure from postnatal day 4 (PN4) through PN9 significantly reduced levels of
      NAA and taurine in the cerebellum and striatum, and induced sex-dependent
      reductions in cerebellar glutamate when measured on PN16. In addition, myo
      inositol was significantly increased in cerebellum. The frontal cortex and
      hippocampus were virtually unaffected by this neonatal alcohol exposure.
      CONCLUSION: Results of this research may have implications for understanding the
      underlying neurobiology associated with FASDs and aid in testing treatments in
      the future. Ongoing studies are assessing the developmental persistence of and/or
      maturational recovery from these changes.

PMID- 18631321
TI  - Nordihydroguaiaretic acid and aspirin increase lifespan of genetically
      heterogeneous male mice.
AB  - The National Institute on Aging's Interventions Testing Program was established
      to evaluate agents that are purported to increase lifespan and delay the
      appearance of age-related disease in genetically heterogeneous mice. Up to five
      compounds are added to the study each year and each compound is tested at three
      test sites (The Jackson Laboratory, University of Michigan, and University of
      Texas Health Science Center at San Antonio). Mice in the first cohort were
      exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N
      tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was
      sufficient to detect a 10% difference in lifespan in either sex,with 80% power,
      using data from two of the three sites. Pooling data from all three sites, a log
      rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased
      lifespan of male mice. Comparison of the proportion of live mice at the age of
      90% mortality was used as a surrogate for measurement of maximum lifespan;neither
      NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test.
      Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite
      suggest that the observed lack of effects of NDGA or aspirin on life span in
      females could be related to gender differences in drug disposition or metabolism.
      Further studies are warranted to find whether NDGA or aspirin, over a range of
      doses,might prove to postpone death and various age-related outcomes reproducibly
      in mice.

PMID- 18631323
TI  - Effects of CRF1-receptor and opioid-receptor antagonists on dependence-induced
      increases in alcohol drinking by alcohol-preferring (P) rats.
AB  - BACKGROUND: Selective breeding of rats over generations and induction of alcohol
      dependence via chronic vapor inhalation both enhance alcohol consumption in
      animal models. The purpose of this study was to determine whether dependence
      induced increases in alcohol consumption by P rats is sensitive to naltrexone, a
      general opioid receptor antagonist (but with highest affinity at the mu-opioid
      receptor at low doses), and the recently characterized small molecule CRF(1)
      receptor antagonist MPZP (N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)
      2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine). METHODS: P rats (n = 20) were
      trained to respond for alcohol and water in a 2-lever operant situation during
      daily 30-minute sessions. P rats were then matched for alcohol intake and exposed
      to chronic intermittent alcohol vapor (n = 10) or ambient air (n = 10) for
      approximately 10 weeks. All rats were then administered MPZP and naltrexone in 2
      separate and consecutive Latin-square designs. RESULTS: MPZP attenuated
      dependence-induced increases in alcohol intake by P rats while having no effect
      on alcohol consumption by nondependent controls. Conversely, operant alcohol
      responding was reduced similarly in dependent and nondependent P rats by
      naltrexone. CONCLUSIONS: These results confirm a role for brain CRF(1)-receptor
      systems in dependence-induced changes in the reinforcing properties of alcohol,
      and CRF(1)-receptor blockade appears to suppress dependence-induced drinking at
      lower doses in P rats relative to other rat lines. Therefore, brain CRF(1)
      receptor systems are important in the regulation of dependence-induced alcohol
      consumption, whereas brain opioid systems are important in the regulation of
      basal alcohol consumption by rats.

PMID- 18631324
TI  - The role of behavioral impulsivity in the development of alcohol dependence: a 4
      year follow-up study.
AB  - BACKGROUND: Although many studies have established a close relation between
      impulsivity and alcohol use disorders, little is known about the role of
      behavioral impulsivity in the development of these disorders. OBJECTIVES: To
      determine the role of 2 laboratory paradigms of impulsivity in the development of
      alcohol use disorders. METHODS: Follow-up study carried out with 471 participants
      diagnosed as heavy drinkers (HD) and followed-up for 4 years. Initially, they
      were compared with a healthy control group. Assessment of behavioral impulsivity
      was carried out with the Continuous Performance Test (CPT), and the Stop-Signal
      Task (SST) assessed behavioral inhibitory control. Differential reinforcement for
      low-rate responding (DRLR) was used to evaluate the delay reward dimension. The
      Structured Clinical Interview (SCID-DSM-IV) was used to diagnose alcohol
      dependence. RESULTS: The HD performed worse than the control group in all the
      behavioral tests of impulsivity. Performance in DRLR was the only behavioral
      impulsivity test that classified the HD correctly compared to controls. Logistic
      regression analysis indicated that performance on SST was a significant predictor
      [odds = 1.52(CI = 1.08-2.31)] of developing alcohol dependence. CONCLUSIONS: Our
      results support the relation between behavioral impulsivity and alcohol use
      disorders. The paradigm related to delay of reward may be a factor associated
      with the use of alcohol and the incapacity to control inhibition as dependence
      develops.

PMID- 18631325
TI  - Treatment of idiopathic sclerosing inflammation of the orbit (myositis) with
      infliximab.
AB  - PURPOSE: We report the successful use of infliximab in a young patient with
      idiopathic sclerosing orbital inflammation (myositis). METHODS: We describe the
      patient's medical records and review the literature. RESULTS: Idiopathic myositis
      in this patient could not be satisfactorily treated with corticosteroids or
      chemotherapy. Biopsy showed sclerosing orbital inflammation. The patient had a
      prompt and sustained response with infliximab and methotrexate treatment.
      CONCLUSIONS: Infliximab and methotrexate might be considered in patients with
      idiopathic sclerosing orbital inflammation (myositis).

PMID- 18631326
TI  - Intravitreal bevacizumab for choroidal neovascularization in toxoplasmosis.

PMID- 18631327
TI  - Macular microcirculation in hypertensive patients with and without branch retinal
      vein occlusion.
AB  - PURPOSE: Our purpose was to determine whether a reduction in blood flow velocity
      (BFV) in the perifoveal capillaries is involved in the pathogenesis of branch
      retinal vein occlusion (BRVO) in patients with hypertension. METHODS: Subjects
      included hypertensive patients with (n = 12) and without (n = 16) BRVO and
      healthy volunteers (n = 16). Perifoveal BFV was measured by the tracing method
      using fluorescein angiography and a scanning laser ophthalmoscope. Logistic
      regression analysis was performed to assess factors that influenced the presence
      or absence of BRVO. RESULTS: Mean BFV showed a significant decrease across the
      three groups (healthy controls: 1.49 +/- 0.11 mm/second; hypertensive patients
      without BRVO: 1.36 +/- 0.12 mm/second; hypertensive patients with BRVO: 1.16 +/-
      0.24 mm/second; p(trend) < 0.001). Multivariate logistic regression analysis
      showed that BFV was a significant risk factor for the presence of BRVO.
      CONCLUSIONS: Perifoveal capillary BFV is reduced in hypertensive patients with
      and without BRVO. It is possible that a decrease in BFV may be involved in the
      occurrence of BRVO. Measurement of perifoveal capillary BFV may be useful for
      investigating the pathogenesis and progression of BRVO.

PMID- 18631328
TI  - Increased retinopathy occurrence in type 1 diabetes patients with increased serum
      levels of the advanced glycation endproduct hydroimidazolone.
AB  - PURPOSE: We aimed to investigate associations between serum levels of the
      advanced glycation endproduct methylglyoxal-derived hydroimidazolone (MG-H1) and
      retinopathy in a sample of patients with type 1 diabetes. METHODS: We conducted a
      cross-sectional study in a Scandinavian ophthalmology outpatient clinic on 61
      randomly selected patients with type 1 diabetes. Blood samples and retinal
      photographs were taken at the same visit. Serum levels of hydroimidazolone
      immunoreactivity were determined using an immunoassay, and levels of retinopathy
      were determined from seven standard field stereo photographs of each eye
      according to the ETDRS method. Results were compared between patients with and
      without retinopathy. RESULTS: Hydroimidazolone quartiles were significantly
      associated with retinopathy (p = 0.013). The most profound increase in occurrence
      of retinopathy was observed from the lowest to the second-lowest hydroimidazolone
      quartile. Adjusted for duration of diabetes using logistic regression, a
      significant difference in the presence of retinopathy was found when comparing
      the lowest quartile with the rest (p = 0.022). CONCLUSIONS: In our patients with
      type 1 diabetes, serum levels of hydroimidazolone were found to be associated
      with retinopathy. This is in keeping with findings in a larger sample of patients
      with type 2 diabetes.

PMID- 18631329
TI  - Comparison of two partial coherence interferometers for corneal pachymetry in
      high myopia and after LASIK.
AB  - PURPOSE: We aimed to compare the Haag-Streit optical low-coherence reflectometry
      (OLCR) pachymeter and the Zeiss Anterior Chamber Master (ACMaster) for measuring
      central corneal thickness (CCT) in high myopes and after laser in situ
      keratomileusis (LASIK) for myopia. METHODS: Central corneal thickness was
      measured in 55 eyes of 30 myopic subjects (spherical equivalent refraction of -
      5.25 D to - 10.75 D, maximal astigmatism of - 2 D), and in 37 eyes of 21 patients
      3 months after LASIK for myopia (preoperative spherical equivalent refraction of 
      6.0 D to - 10.75 D, maximal astigmatism of - 2 D). All measurements were
      performed with the Haag-Streit OLCR pachymeter and the Zeiss ACMaster, using
      group refractive indices of 1.376 and 1.3851, respectively. Thickness
      measurements were compared using paired t-tests, Pearson's correlation, linear
      regression and Bland-Altman plots. RESULTS: In myopic subjects, CCT measured 531
      +/- 28 microm and 533 +/- 27 microm with the OLCR pachymeter and the ACMaster,
      respectively (p < 0.01); all measurements correlated closely (r = 0.99, p <
      0.01). In LASIK-treated eyes, CCT measured 472 +/- 24 microm using the OLCR
      pachymeter and 475 +/- 23 microm using the ACMaster (p < 0.01), again with close
      correlation between the two instruments (r = 0.99, p < 0.01). CONCLUSIONS:
      Measurements of CCT in high myopes and after myopic LASIK were very similar with
      the Haag-Streit OLCR pachymeter and the Zeiss ACMaster. Using the current group
      refractive indices, the observed difference between the two instruments of < 3
      microm is of little clinical importance. Thus, it would seem safe to use the OLCR
      pachymeter and the ACMaster interchangeably for CCT measurements in myopia as
      well as after myopic LASIK.

PMID- 18631330
TI  - Retinal haemorrhages in shaken baby syndrome.

PMID- 18631331
TI  - Clinical characteristics and visual outcome of non-traumatic suprachoroidal
      haemorrhage in Taiwan.
AB  - PURPOSE: This study aimed to evaluate the clinical features and visual outcomes
      of non-traumatic suprachoroidal haemorrhage (SH) in Taiwan. METHODS: We report a
      retrospective, non-comparative, interventional case series study carried out in
      an institutional setting. Thirty-nine eyes with non-traumatic SH were studied
      using a new system for grading the severity of SH. The aetiologies of SH were
      analysed. The correlations between grades and prognoses of SH were studied.
      Multiple logistic regression was used to assess factors associated with final
      visual outcome. RESULTS: Conditions causing SH in the eyes considered in this
      study included cataract surgery (43.59%), age-related macular degeneration (AMD)
      (17.95%), filtering operation and vitrectomy (both 10.26%), scleral buckling
      (5.13%) and others. Twelve eyes (12/39, 30.77%) had a final visual outcome of no
      light perception. Only 12 eyes (12/39, 30.77%) had final visual acuity (VA) >
      4/200. Grade of SH correlated significantly with need for surgical drainage and
      with final visual outcome (Spearman rank correlations 0.313 and - 0.408, p =
      0.010 and p = 0.00317, respectively). 'Good' and 'poor' final VA was
      significantly associated with VA at the time of SH (multiple logistic regression
      coefficients 2.132 and - 2.809, p = 0.015 and p = 0.008, respectively), as well
      as initial retinal detachment (multiple logistic regression coefficients - 2.267
      and 2.223, p = 0.036 and p = 0.006, respectively). Higher grades of SH and
      increased age were associated with poor final visual outcome (multiple logistic
      regression coefficients - 1.332 and - 0.122, p = 0.013 and p = 0.022,
      respectively). CONCLUSIONS: Suprachoroidal haemorrhage is a devastating ocular
      problem. Complications of intraoperative surgery and AMD are common causes. The
      new SH grading system provides a simple method for evaluating the need for
      drainage and for predicting visual prognosis. Visual acuity and retinal
      detachment at the time of SH are major factors associated with good and poor
      final VA, respectively.

PMID- 18631332
TI  - Efficacy of olopatadine HCI 0.1%, ketotifen fumarate 0.025%, epinastine HCI
      0.05%, emedastine 0.05% and fluorometholone acetate 0.1% ophthalmic solutions for
      seasonal allergic conjunctivitis: a placebo-controlled environmental trial.
AB  - PURPOSE: We aimed to compare the clinical efficacy and ocular surface variables
      of olopatadine, ketotifen fumarate, epinastine, emedastine and fluorometholone
      acetate ophthalmic solutions in preventing the signs and symptoms of seasonal
      allergic conjunctivitis (SAC). METHODS: This was a prospective, randomized,
      double-blinded and placebo-controlled study. A total of 100 patients with SAC
      were randomly assigned to one of five groups, in which they were administered
      olopatadine, ketotifen fumarate, epinastine, emedastine or fluorometholone
      acetate, instilled twice daily for 2 weeks. One eye of each patient was treated
      with the study drug and the other was treated with a placebo. Signs and symptoms
      of allergic conjunctivitis (itching, redness, tearing, chemosis and eyelid
      swelling) were scored on a 4-point scale. Each symptom was assessed at baseline
      and then again after 1 and 2 weeks of treatment. Ocular surface variables were
      assessed by conjunctival impression cytology. RESULTS: At weeks 1 and 2, all
      antiallergic agents were significantly more effective than placebo in alleviating
      itching, redness, tearing, chemosis and eyelid swelling. Fluorometholone acetate
      was significantly less effective than the other agents in reducing itching and
      redness at all control visits. Ocular surface findings by impression cytology
      improved significantly after all treatments compared with placebo. CONCLUSIONS:
      In patients with SAC, olopatadine, ketotifen, epinastine and emedastine are more
      efficacious than fluorometholone acetate in preventing itching and redness. All
      the antiallergic agents gave similar results in terms of reducing tearing,
      chemosis and eyelid swelling. Our data showed that impression cytology parameters
      improved after treatment with antiallergic agents in patients with SAC.

PMID- 18631333
TI  - Long-term visual prognosis of corneal and ocular surface surgery in patients with
      congenital aniridia.
AB  - PURPOSE: To evaluate the long-term visual prognosis of corneal and ocular surface
      surgery in patients with congenital aniridia. METHODS: Retrospective comparative
      interventional case series on 88 eyes of 45 patients with congenital aniridia
      treated and/or operated on from 1956 to present. Corneal and ocular surface
      findings were identified and patients were classified into operated (group I) or
      not operated (group II). Long-term best-ever best-corrected visual acuity (BCVA),
      final BCVA and long-term delta BCVA (long-term best-ever BCVA - final BCVA) were
      recorded and compared between the two groups, and between the limbal transplant
      (LT) (group I-A) and the penetrating keratoplasty (PK) (group I-B) patients.
      Postoperative results were also compared. RESULTS: Limbal insufficiency was
      present in 58% of eyes and dense central corneal opacities were present in 27% of
      eyes. As a primary surgery, limbal allograft was performed in 10 eyes and PK in
      13 eyes. The mean long-term follow-up times were 23 years in group I and 16 years
      in group II. The mean long-term delta BCVA was 0.032 in group I and 0.028 in
      group II. Comparisons of the VA means were insignificant (long-term best-ever,
      final BCVA and long-term delta BCVA). When comparing the LT and PK groups, mean
      long-term delta BCVA was 0.0328 in group I-A and 0.0382 in group I-B. Mean
      postoperative delta BCVA was 0.028 in group I-A and 0.048 in group I-B. We found
      no statistical significance between the LT and the PK groups as regards long-term
      postoperative BCVA results. CONCLUSION: Long-term visual prognosis does not
      differ whether or not the patient undergoes surgery for aniridic keratopathy. LT
      and PK have comparable results over 5 years of follow-up because of the eventual
      failure of transplanted allografts.

PMID- 18631334
TI  - Trabeculectomy with an active postoperative regimen: results and resource
      utilization.
AB  - PURPOSE: To evaluate intraocular pressure (IOP) and resource utilization after
      trabeculectomy, using an active postoperative regimen, in a Swedish population.
      METHODS: A retrospective analysis was performed on the patient charts of all
      patients who underwent trabeculectomy in a Swedish university hospital during 1
      year (November 2000-December 2001). Trabeculectomy was performed in 34 eyes and
      trabeculectomy in combination with phacoemulsification in 10 eyes. Intraocular
      pressure, visual acuity, complications and numbers of injections of 5
      fluorouracil, suture removal, needling procedures and visits to ophthalmologists
      were recorded for 2 years. RESULTS: Mean IOP before surgery was 30.4 mmHg
      (standard deviation [SD] 9.5) in eyes with capsular glaucoma and 28.7 mmHg (SD
      9.3) in eyes with primary open-angle glaucoma. Mean IOP after 2 years was 15.3
      mmHg (SD 3.9) in all eyes. Intraocular pressure of < 18 mmHg was achieved in 65%
      of the eyes after 2 years, as was IOP < or = 13 mmHg in 37%. Flap or suture
      manipulation was performed in 41 of 44 eyes. Needling procedures were carried out
      a mean of 2.3 times in 31 eyes. The mean number of visits to an ophthalmologist
      was 14.1 during the first postoperative year and 4.4 during the second.
      CONCLUSIONS: The results were encouraging, with few complications and modest
      resource utilization.

PMID- 18631335
TI  - Comparison of dynamic contour tonometry with Goldmann applanation tonometry in
      glaucoma practice.
AB  - PURPOSE: To compare intraocular pressure (IOP) readings taken using dynamic
      contour tonometry (DCT) with IOP readings taken with Goldmann applanation
      tonometry (GAT) in eyes with glaucoma or ocular hypertension. METHODS: The
      present study included 100 eyes in 100 patients with glaucoma or ocular
      hypertension. After pachymetry DCT and GAT were performed. Intraocular pressures
      as measured with DCT and GAT were compared with one another and with central
      corneal thickness (CCT). RESULTS: Mean DCT IOP measurements (20.1 +/- 4.3 mmHg)
      were significantly (p < 0.001) higher than GAT IOP values (17.9 +/- 4.7 mmHg).
      The mean difference between DCT and GAT measurements was 2.1 mmHg (range -3.4 to
      9.7 mmHg). The difference followed a normal distribution. Measurements made with
      DCT and GAT correlated significantly with one another (Spearman's rho = 0.761, p
      < 0.001). Neither GAT nor DCT measurements showed a significant correlation with
      CCT (537 +/- 39 microm, range 458-656 microm). Multivariate regression analysis
      has shown that the difference between DCT and GAT is influenced significantly by
      ocular pulse amplitude (r = -0.334, p = 0.001) and it is not influenced by CCT (r
      = -0.106, p = 0.292). CONCLUSIONS: In eyes with glaucoma or ocular hypertension,
      DCT facilitates suitable and reliable IOP measurements which are in good
      concordance with GAT readings. Variation in CCT cannot by itself explain the
      differences in measurements taken with DCT and GAT in a number of eyes.

PMID- 18631336
TI  - Progression of tractional retinal detachment following intravitreal bevacizumab.

PMID- 18631337
TI  - Povidone iodine causes opacification of silicone intraocular lens implants.
AB  - PURPOSE: Four cases of silicone intraocular lens (IOL) opacifications presented
      at a routine cataract service at a UK district general hospital. A systematic
      investigation was performed to identify and eliminate the causative factor.
      METHODS: An experiment was set up to determine the role of a chemically induced
      IOL injury. Silicone IOLs were exposed to the various chemical agents used during
      cataract surgery. One IOL was not exposed to any chemicals and was used as a
      control. The samples were then photographed with the same camera settings against
      the same background in a medical photography studio. RESULTS: All samples
      photographed using this technique were clear as the unexposed control IOL, except
      the IOLs that had come into contact with povidone iodine (PI). Exposure to higher
      concentrations of PI appears to give a greater opacification and staining--a
      graded effect. CONCLUSION: While the toxic effects of PI on corneal endothelial
      health is well recognized, as far as the authors are aware no reports exists on
      the possible harmful effects of PI on IOLs. The results from the current study
      suggest that exposure of silicone IOLs to even small volumes of 5% PI can lead to
      IOL opacifying effects. Further studies are needed to determine the toxic effects
      of PI on all IOL materials. However, based on the results of our study, we
      strongly recommend extreme caution in the use of PI as prophylaxis against
      infection at the conclusion of cataract surgery and recommend great care to
      ensure complete wound closure.

PMID- 18631338
TI  - History of ophthalmology: a distinguished or extinguished field of scholarly
      activity?

PMID- 18631339
TI  - Stix test for bacterial conjunctivitis.

PMID- 18631340
TI  - Correlation of 8-isoprostane, interleukin-6 and cardiac functions with clinical
      score in childhood obstructive sleep apnoea.
AB  - OBJECTIVE: Adeno-tonsillar hypertrophy is the commonest cause of childhood
      obstructive sleep apnoea (OSA). Our aim of the study is to correlate the severity
      of OSA with levels of 8-isoprostane and interleukin-6 (IL-6) and with cardiac
      diastolic dysfunctions. METHODS: Forty children with adenoidal hypertrophy and 20
      control children were recruited. The OSA clinical score was evaluated and IL-6
      and 8-isoprostane were measured in exhaled breath condensate. The cardiac
      functions were evaluated by conventional and tissue Doppler echocardiography
      (TDE). RESULTS: Higher concentrations of isoprostane-8 and IL-6 were found in
      group with clinical score >40 (58.595 +/- 2.86 pg/mL and 38 +/- 1.77 pg/mL,
      respectively) than in control group (34.9 +/- 1.5 pg/mL and 7.02 +/- 0.3 pg/mL,
      respectively) {p < 0.0001*}. There was positive correlation between level of
      isoprostane-8 and IL-6 and value of clinical score {p < 0.0001*} and also with
      the degree of the cardiac dysfunction in those children. CONCLUSION: The severity
      of OSA as indicated by clinical score was positively correlated with degree of
      elevation of 8-Isoprostane and IL-6 in breath condensate of children with OSA and
      also with degree of cardiac dysfunction. Echocardiography and tissue Doppler
      modality are advised to examine these children.

PMID- 18631341
TI  - Incidence and risk factors of lower respiratory tract illnesses during infancy in
      a Mediterranean birth cohort.
AB  - AIM: To investigate the incidence rate, viral respiratory agents and determinants
      of lower respiratory tract illnesses (LRTIs) in infants younger than 1 year.
      METHODS: A total of 487 infants were recruited at birth for the Asthma
      Multicenter Infant Cohort Study in Barcelona (Spain). Cases of LRTIs were
      ascertained through an active register including a home visit and viral test in
      nasal lavage specimens during the first year of life. Cotinine in cord blood,
      household aeroallergens, indoor NO(2) and maternal and neonatal IgE were
      measured. Other maternal and infants' characteristics were obtained from
      structured questionnaires. RESULTS: The incidence rate of at least one LRTI was
      38.7 infants per 100 persons-years. The most frequently isolated viral agent was
      respiratory syncytial virus (44.7%). The risk of LRTIs was higher in infants with
      a maternal history of asthma and in those with siblings (OR = 2.4; 95% CI: 0.98
      6.08 and OR = 1.8; 95% CI: 1.04-3.21, respectively). The risk of LRTIs was lower
      in infants who were breast fed for more than 12 weeks (OR = 0.26; 95% CI: 0.26
      0.86) and in those from a low socioeconomic class (OR = 0.16; 95% CI: 0.06-0.42).
      CONCLUSION: Viral LRTIs are frequent in infants younger than 1 year of age and
      there is an inter-relationship between maternal asthma, siblings, breast feeding
      and socioeconomic status.

PMID- 18631342
TI  - Do drugs that block transforming growth factor beta reduce posthaemorrhagic
      ventricular dilatation in a neonatal rat model?
AB  - AIM: Posthaemorrhagic ventricular dilatation (PHVD) after intraventricular
      haemorrhage (IVH) remains a significant problem in preterm infants. No treatment
      has reduced the need for cerebrospinal fluid (CSF) diversion. Considerable
      evidence implicates transforming growth factor-beta (TGF-beta) in the
      pathogenesis of PHVD. Pirfenidone and losartan reduce TGF-beta expression and
      decrease postinflammatory fibrosis in the lungs, kidneys, heart and liver. They
      have excellent CSF and brain penetration. We hypothesized that administration of
      pirfenidone or losartan would reduce ventricular dilatation. METHODS: Ninety-two
      rat pups underwent intraventricular blood injection on postnatal days (PN) 7 and
      8, and were randomised to pirfenidone, losartan or water by gavage for 14 days.
      Neuromotor testing was carried out twice weekly. After sacrifice at PN21,
      ventricular area was measured on coronal sections using image-analysis software.
      RESULTS: Ninety-five percent of animals undergoing IVH developed PHVD.
      Ventricular size was not significantly different between animals receiving either
      drug or water. Neuromotor testing at PN14 was significantly worse in IVH animals
      than in controls; neither drug improved performance in IVH animals. CONCLUSION:
      Drugs that block TGF-beta do not reduce ventricular dilatation in this model.
      Further study is required to identify other cytokine targets and to determine how
      PHVD differs from postinflammatory fibrosis in other organs.

PMID- 18631343
TI  - High prevalence of allergic diseases and sensitization in a low allergen country.
AB  - BACKGROUND: The prevalence of adult atopic diseases in Iceland is lower than in
      other West European countries, despite an affluent lifestyle, but limited data
      are available on children. The main aim of this study was to investigate the
      prevalence of atopic diseases and sensitivity to common allergens in 10- to 11
      year-old Icelandic schoolchildren as part of phase II of the International Study
      of Asthma and Allergies in Children (ISAAC). METHODS: Nine hundred and forty-six
      children and their parents answered a questionnaire about atopic diseases. Skin
      prick tests with six allergens were performed on 773 children and they were
      examined for signs of atopic dermatitis (AD). RESULTS: The 12-month prevalence of
      allergic rhinoconjunctivitis and asthma was 11.5% and 8.9% respectively. The
      reported prevalence of AD was 27%, but only 9.2% had signs when inspected. A
      positive skin prick test (SPT) was found in 24.4% of the children, that is 18.8%
      to grass, 12.9% to cat, 3.6% to trees, 3.0% to Dermatophagoides pteronyssinus,
      1.4% to D. farinae and 0.5% to Alternaria. CONCLUSION: The high prevalence of
      atopic diseases in children at 10-11 years is surprising, as the prevalence in
      adults is low in Iceland. The findings resemble those in developing countries.
      Iceland has had an affluent lifestyle for a considerable time, but the absence of
      dust mites, low pet ownership and relatively low pollen counts in the country
      raise doubts about the role of exposure levels in the development of
      sensitization and atopic diseases.

PMID- 18631344
TI  - Sustained response after reduced-intensity conditioning allogeneic stem cell
      transplantation for patients with relapsed peripheral T-cell non-Hodgkin
      lymphoma.

PMID- 18631346
TI  - Sublingual immunotherapy in youngsters: adherence in a randomized clinical trial.
AB  - BACKGROUND: Adherence is essential for effective treatment. Although several
      trials on the efficacy of sublingual immunotherapy (SLIT) in youngsters have been
      published, few contain data on medication intake. OBJECTIVE: We aimed to quantify
      adherence both to study protocol and medication intake as well as to identify
      factors that may influence adherence to SLIT in youngsters with
      rhinoconjunctivitis. METHODS: Two hundred and four youngsters (6-18 years) with
      hayfever participated in a randomized controlled trial and used grass pollen
      extract or placebo for 2 years. The primary outcome of the trial was the mean
      daily total rhinoconjunctivitis symptom score in the second grass pollen season.
      Participants having completed the follow-up were considered adherent to the study
      protocol. Adherence to medication intake was assessed by weighing the study
      medication. Participants who completed the follow-up and used > or = 80% of the
      prescribed medication were considered adherent to medication intake. Patient-,
      disease- and treatment-related factors were analysed. RESULTS: One hundred and
      fifty-four youngsters completed the study. The main reason for discontinuation
      was the inability to take medication according to schedule. Drop-outs were older,
      had more difficulty following the medication instructions and their overall
      evaluation of the treatment effect was lower. The number and reasons for drop-out
      did not differ between treatment groups. In total, 77% of the participants was
      adherent to medication intake. Self-reported adherence was 99%. Non-adherent
      participants experienced more severe symptoms before the trial. Symptom scores
      did not differ between adherent and non-adherent participants. In adherent as
      well as non-adherent participants, no difference was found between verum and
      placebo group with respect to symptom scores. CONCLUSION: Adherence to both study
      protocol and medication intake was good. Drop-out was affected by age, evaluation
      of the treatment effect and medication instructions. Non-adherence to medication
      intake was influenced by the severity of the disease before the trial. The
      ineffectiveness of SLIT could not be explained by non-adherence.

PMID- 18631345
TI  - Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics
      in pregnancy increases cord blood interferon-gamma and breast milk transforming
      growth factor-beta and immunoglobin A detection.
AB  - BACKGROUND: This study explored the effects of maternal probiotic supplementation
      on immune markers in cord blood (CB) and breast milk. METHODS: CB plasma and
      breast milk samples were collected from a cohort of women who had received daily
      supplements of either 6 x 10(9) CFU/day Lactobacillus rhamnosus HN001 (n=34), 9 x
      10(9) CFU/day Bifidobacterium lactis HN019 (n=35) or a placebo (n=36) beginning 2
      5 weeks before delivery and continuing for 6 months in lactating women. CB plasma
      and breast milk (collected at 3-7 days, 3 months and 6 months postpartum) were
      assayed for cytokines (IL-13, IFN-gamma, IL-6, TNF-alpha, IL-10, TGF-beta1) and
      sCD14. Breast milk samples were also assayed for total IgA. RESULTS: Neonates of
      mothers who received a probiotic had higher CB IFN-gamma levels (P=0.026), and a
      higher proportion had detectable blood IFN-gamma levels, compared with the
      placebo group (P=0.034), although levels were undetectable in many infants. While
      this pattern was evident for both probiotics, when examined separately only the
      L. rhamnosus HN001 group showed statistically significant higher IFN-gamma levels
      (P=0.030) compared with the placebo group. TGF-beta1 levels were higher in early
      breast milk (week 1) from the probiotic groups (P=0.028). This was evident for
      the B. lactis HN019 group (P=0.041) with a parallel trend in the L. rhamnosus
      HN001 group (P=0.075). Similar patterns were seen for breast milk IgA, which was
      more readily detected in breast milk from both the B. lactis HN019 (P=0.008) and
      the L. rhamnosus HN001 group (P=0.011). Neonatal plasma sCD14 levels were lower
      in the B. lactis HN019 group compared with the placebo group (P=0.041).
      CONCLUSION: The findings suggest that supplementation with probiotics in
      pregnancy has the potential to influence fetal immune parameters as well as
      immunomodulatory factors in breast milk.

PMID- 18631347
TI  - Loss of classical transient receptor potential 6 channel reduces allergic airway
      response.
AB  - BACKGROUND: Non-selective cation influx through canonical transient receptor
      potential channels (TRPCs) is thought to be an important event leading to airway
      inflammation. TRPC6 is highly expressed in the lung, but its role in allergic
      processes is still poorly understood. OBJECTIVE: The purpose of this study was to
      evaluate the role of TRPC6 in airway hyperresponsiveness (AHR) and allergic
      inflammation of the lung. METHODS: Methacholine-induced AHR was assessed by head
      out body plethysmography of wild type (WT) and TRPC6(-/-) mice. Experimental
      airway inflammation was induced by intraperitoneal ovalbumin (OVA) sensitization,
      followed by OVA aerosol challenges. Allergic inflammation and mucus production
      were analysed 24 h after the last allergen challenge. RESULTS: Methacholine
      induced AHR and agonist-induced contractility of tracheal rings were increased in
      TRPC6(-/-) mice compared with WT mice, most probably due to compensatory up
      regulation of TRPC3 in airway smooth muscle cells. Most interestingly, when
      compared with WT mice, TRPC6(-/-) mice exhibited reduced allergic responses after
      allergen challenge as evidenced by a decrease in airway eosinophilia and blood
      IgE levels, as well as decreased levels of T-helper type 2 (Th2) cytokines (IL-5,
      IL-13) in the bronchoalveolar lavage. However, lung mucus production after
      allergen challenge was not altered by TRPC6 deficiency. CONCLUSIONS: TRPC6
      deficiency inhibits specific allergic immune responses, pointing to an important
      immunological function of this cation channel in Th2 cells, eosinophils, mast
      cells and B cells.

PMID- 18631348
TI  - Toll-like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate
      ovalbumin-specific allergic airway disease: role of MyD88 adaptor molecule and
      interleukin-12/interferon-gamma axis.
AB  - BACKGROUND: Epidemiological and experimental data suggest that bacterial
      lipopolysaccharides (LPS) can either protect from or exacerbate allergic asthma.
      Lipopolysaccharides trigger immune responses through toll-like receptor 4 (TLR4)
      that in turn activates two major signalling pathways via either MyD88 or TRIF
      adaptor proteins. The LPS is a pro-Type 1 T helper cells (Th1) adjuvant while
      aluminium hydroxide (alum) is a strong Type 2 T helper cells (Th2) adjuvant, but
      the effect of the mixing of both adjuvants on the development of lung allergy has
      not been investigated. OBJECTIVE: We determined whether natural (LPS) or
      synthetic (ER-803022) TLR4 agonists adsorbed onto alum adjuvant affect allergen
      sensitization and development of airway allergic disease. To dissect LPS-induced
      molecular pathways, we used TLR4-, MyD88-, TRIF-, or IL-12/IFN-gamma-deficient
      mice. METHODS: Mice were sensitized with subcutaneous injections of ovalbumin
      (OVA) with or without TLR4 agonists co-adsorbed onto alum and challenged with
      intranasally with OVA. The development of allergic lung disease was evaluated 24
      h after last OVA challenge. RESULTS: Sensitization with OVA plus LPS co-adsorbed
      onto alum impaired in dose-dependent manner OVA-induced Th2-mediated allergic
      responses such as airway eosinophilia, type-2 cytokines secretion, airway hyper
      reactivity, mucus hyper production and serum levels of IgE or IgG1 anaphylactic
      antibodies. Although the levels of IgG2a, Th1-affiliated isotype increased,
      investigation into the lung-specific effects revealed that LPS did not induce a
      Th1 pattern of inflammation. Lipopolysaccharides impaired the development of Th2
      immunity, signaling via TLR4 and MyD88 molecules and via the IL-12/IFN-gamma
      axis, but not through TRIF pathway. Moreover, the synthetic TLR4 agonists that
      proved to have a less systemic inflammatory response than LPS also protected
      against allergic asthma development. CONCLUSION: Toll-like receptor 4 agonists co
      adsorbed with allergen onto alum down-modulate allergic lung disease and prevent
      the development of polarized T cell-mediated airway inflammation.

PMID- 18631349
TI  - Exposure to environmental bacteria may have differing effects on tumour necrosis
      factor-alpha and interleukin-6-producing capacity in infancy.
AB  - BACKGROUND: Our previous study showed an association between increased
      concentration of endotoxin in house dust and elevated IFN-gamma responses in
      neonates. The impact of other microbial agents on immune responses in infancy is
      poorly known. OBJECTIVE: To examine whether stimulated cytokine responses of
      mothers and their children are associated with concentrations of other microbial
      markers in addition to endotoxin in house dust samples. METHODS: Mitogen
      stimulated production of IFN-gamma, IL-4, IL-6 and TNF-alpha was measured in cord
      blood and in peripheral blood of mothers (n=29) and their children (n=29) 3
      months after birth. Gas chromatography mass spectrometric analysis was applied to
      measure the concentrations of ergosterol (marker of fungal biomass), muramic acid
      (indicating the presence of Gram-positive bacteria) and 3-hydroxy fatty acids
      (C(10:0)-C(14:0), indicating the presence of Gram-negative bacteria) in house
      dust. Endotoxin was determined with Limulus assay. RESULTS: Significant mother-to
      child correlations were observed in stimulated production of TNF-alpha and IL-6 3
      months after birth. 3-hydroxy fatty acid (C(10:0)-C(14:0)) levels in bed dust
      were inversely associated with the production of TNF-alpha and IL-6 in blood
      samples of mothers and their 3-month-old children. High concentrations of muramic
      acid in floor dust were related to increased production of TNF-alpha and IL-6 at
      the age of 3 months. In contrast to endotoxin, none of the other microbial
      markers were significantly associated with enhanced IFN-gamma-producing capacity
      from birth to 3 months. CONCLUSIONS: Exposure to Gram-negative bacteria and their
      components may be associated with down-regulated immune responses in early
      infancy, indicated as an impaired production of pro-inflammatory cytokines
      following mitogen stimulation. Gram-positive bacteria and their constituents seem
      to have opposite effects. Of the measured markers, exposure to bioactive
      endotoxin appears to have the strongest impact on T-helper type 1 responses.

PMID- 18631350
TI  - Prior SO2 exposure promotes airway inflammation and subepithelial fibrosis
      following repeated ovalbumin challenge.
AB  - BACKGROUND: Exposure to allergens or air pollutants often leads to asthma
      exacerbations associated with aggravation of airway inflammation. Although,
      repeated allergen challenge often induces chronic allergic airway inflammation
      (CAAI) and airway remodelling, yet, the effects of brief exposure to air
      pollutants such as SO(2) on development of CAAI and airway remodelling remain to
      be clarified. OBJECTIVE: The aim of the experiment was to investigate the effects
      of acute neutrophilic airway inflammation induced by brief exposure to SO(2) on
      development of CAAI and subepithelial fibrosis (SEF) in a murine model of asthma.
      METHODS: Acute airway inflammation was induced by brief exposure to 50 p.p.m.
      SO(2) (1 h/d, 3 days). CAAI and SEF in BALB/c mice were induced by repeated
      challenge with ovalbumin (OVA) for 5 or 9 weeks with or without prior exposure to
      SO(2). Bronchoalveolar lavage fluid (BALF) eosinophilia as index of CAAI, BALF
      endothelin-1 (ET-1) and TGF-beta1 levels, morphometric evaluation of fibrotic
      area beneath subbasement membrane and lung hydroxyproline content (Hyp) as
      indexes of SEF were monitored. RESULTS: Exposure to SO(2) led to acute
      neutrophilic inflammation and epithelial sloughing with profound elevation of
      BALF ET-1. Repeated OVA challenge resulted in CAAI and SEF along with elevation
      of Hyp, increase of fibrotic area beneath subbasement membrane and elevation of
      BALF TGF-beta1. Preceding SO(2) exposure exaggerated BALF eosinophilia,
      facilitated and enhanced SEF with more significant elevation of BALF ET-1 and TGF
      beta1 levels compared with OVA-challenged mice without prior exposure to SO(2).
      The increase of Hyp was positively correlated with elevation of BALF TGF-beta1
      during CAAI (r=0.842, P<0.01). CONCLUSION: This data demonstrated that SEF
      developed in parallel with severity and time course of CAAI following repeated
      OVA challenge. SO(2)-induced acute epithelial injury and neutrophilic
      inflammation could enhance CAAI and promote SEF, probably through overexpression
      of ET-1 and TGF-beta1.

PMID- 18631351
TI  - Protection from skin test reactivity by helminth infections: Trichuris trichiura
      induces protection in the long term.

PMID- 18631352
TI  - The allergic march in early childhood and beyond.

PMID- 18631353
TI  - Immunochemical characterization of Glycine max L. Merr. var Raiden, as a possible
      hypoallergenic substitute for cow's milk-allergic patients.
AB  - BACKGROUND: Cows' milk allergy (CMA) is the most common cause of food allergy in
      infancy. The only proven treatment is the complete elimination of cows' milk
      proteins (CMPs) from the diet by means of hypoallergenic formulas. Soybean-based
      formulae are widely used although intolerance to soy has been reported to occur
      in 15-40% of infants with CMA. OBJECTIVE: The aim of this work was to analyse the
      in vitro reactivity of the soybean cultivar Raiden, which naturally lacks
      glycinin A(4)A(5)B(3), to evaluate whether this genotype could be a safe CMP
      substitute for CMA patients. METHODS: The reactivity of conventional soybean (CS)
      and Raiden soybean (RS) genotypes and also recombinant glycinin A(4)A(5)B(3) and
      alphabeta-conglycinin with casein-specific monoclonal antibodies and CMP-specific
      polyclonal serum was evaluated by immunoblotting and ELISA. A sequential
      competitive ELISA with the polyclonal antiserum and different soluble inhibitors
      was performed. In addition, an indirect ELISA with sera of atopic children with
      CMA was carried out to analyse the IgE-binding capacity of the different soybean
      components. RESULTS: We have shown that CS contains four components that cross
      react with CMP, while RS has only one. The remaining cross-reactive component in
      RS was identified as alpha-subunit beta-conglycinin. By means of inhibitory
      ELISA, we demonstrated that CS, RS and the alpha-subunit beta-conglycinin
      extracts inhibited the binding of CMP-specific antibodies to the CMP-coated solid
      phase. Finally, we showed that CS, RS and the recombinant proteins were
      recognized by human CMP-specific IgE antibodies. CONCLUSION: This work shows that
      although Raiden has fewer cross-reactive components than conventional soybean, it
      still has a residual cross-reactive component: the alpha-subunit beta
      conglycinin. This reactivity might make this genotype unsuitable to treat CMA and
      also explains adverse reactions to soybean in CMA infants.

PMID- 18631354
TI  - Paraganglioma-like medullary thyroid carcinoma: fine needle aspiration cytology
      features with histological correlation.
AB  - OBJECTIVES: Two cases of an extremely rare paraganglioma-like variant of
      medullary thyroid carcinoma (MTC) are reported. METHODS: The patients were a 65
      year-old male (case 1) and a 14-year-old female (case 2). Unilateral thyroid
      nodule and homolateral cervical lymphadenopathy was present in case 1; bilateral
      thyroid nodules were seen in case 2. Fine needle aspiration cytology (FNAC) was
      performed from thyroid nodules (in both cases) and from a cervical lymph node (in
      case 1). RESULTS: The cytological smears contained predominantly ovoid to
      spindled epithelial cells arranged in cohesive three-dimensional clusters with
      sharp margins; isolated individual cells were seen only rarely. No colloid or
      other material was present in the background. The tumour cells showed significant
      nuclear atypia with occasional bizarre and/or binucleated cells. The nuclear
      chromatin was coarse and granular, sometimes with grooves and intranuclear
      inclusions. The cytoplasm was inconspicuous. Polygonal or triangular cells,
      amyloid and azurophillic cytoplasmic granules were absent in both cases.
      Calcitonin expression was demonstrated in case 2. Histological examination
      confirmed the paraganglioma variant of MTC in both cases. Mutation of RET proto
      oncogene in exon 16 (Met918Thr) - germline in case 2 and somatic in case 1 was
      detected by sequencing of DNA in both cases. CONCLUSIONS: This is the first
      description of cytological findings in the paraganglioma-like variant of MTC.
      Despite its rarity, it can be reliably diagnosed by FNAC if material for
      immunocytochemistry is obtained.

PMID- 18631355
TI  - Primary pulmonary synovial sarcoma - transbronchial needle aspiration is a
      diagnostic approach: a case report with cytological features.

PMID- 18631356
TI  - Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in
      screening for bladder cancer?--experience at Kuwait University.
AB  - OBJECTIVES: This prospective study was undertaken to evaluate nuclear matrix
      protein (NMP22) compared to urine cytology in the detection of bladder cancer and
      also to determine whether indexing suspicious cytology to NMP22 could enhance the
      clinical utility of cytology. METHODS: Cytological findings of voided urine
      collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in
      46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The
      patients were clinically categorized into newly diagnosed cases of transitional
      cell carcinoma (TCC), recurrent TCC, TCC in remission and controls. RESULTS:
      Using histological diagnosis as the gold standard the sensitivity and specificity
      of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology
      were 30% and 87% respectively. If suspicious and malignant cytology were combined
      as positive results the sensitivity increased significantly to 87% while the
      specificity decreased but not significantly to 74%. Suspicious or malignant
      cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of
      87% neither of which was significantly different from cytology alone. There were
      three false positive cases on cytology and 13 false positive cases on NMP22
      assay. There were three false negative cytology and five false negative NMP22
      cases but only one was false negative for both, resulting in a high sensitivity
      (96%) but low specificity (30%) if either positive NMP22 or malignant or
      suspicious cytology was taken as a positive result. CONCLUSION: Combining NMP22
      with malignant or suspicious cytological result improved sensitivity for the
      detection of bladder cancer but with a major decrease in specificity, suggesting
      a potential role in screening rather than diagnosis.

PMID- 18631357
TI  - Fine needle aspiration cytology of malignant mixed tumour of the vulva.

PMID- 18631358
TI  - Cervicovaginal smears in the diagnosis of asymptomatic primary fallopian tube
      carcinoma.

PMID- 18631359
TI  - Phosphorylation of the arginine/serine dipeptide-rich motif of the severe acute
      respiratory syndrome coronavirus nucleocapsid protein modulates its
      multimerization, translation inhibitory activity and cellular localization.
AB  - Coronavirus nucleocapsid protein is abundant in infected cells and participates
      in viral RNA replication and transcription. The central domain of the
      nucleocapsid protein contains several arginine/serine (RS) dipeptides, the
      biological significance of which has not been well investigated. In the present
      study, we demonstrate that the severe acute respiratory syndrome coronavirus
      nucleocapsid protein is phosphorylated primarily within the RS-rich region in
      cells and by SR protein kinase 1 in vitro. The nucleocapsid protein could
      suppress translation and its RS motif is essential for such an activity.
      Moreover, phosphorylation of the RS motif could modulate the translation
      inhibitory activity of the nucleocapsid protein. We further found that RS motif
      phosphorylation did not significantly affect RNA binding of the nucleocapsid
      protein but impaired its multimerization ability. We observed that the
      nucleocapsid protein could translocate to cytoplasmic stress granules in response
      to cellular stress. Deletion or mutations of the RS motif enhanced stress granule
      localization of the nucleocapsid protein, whereas overexpression of SR protein
      kinase 1 inhibited nucleocapsid protein localization to stress granules. The
      nucleocapsid protein lacking the RS motif formed high-order RNP complexes, which
      may also account for its enhanced stress granule localization. Taken together,
      phosphorylation of the severe acute respiratory syndrome-CoV nucleocapsid protein
      modulates its activity in translation control and also interferes with its
      oligomerization and aggregation in stress granules.

PMID- 18631360
TI  - Investigations on the evolutionary conservation of PCSK9 reveal a functionally
      important protrusion.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) interferes with the
      recycling of low-density lipoprotein (LDL) receptor (LDLR). This leads to LDLR
      degradation and reduced cellular uptake of plasma LDL. Naturally occurring human
      PCSK9 loss-of-function mutations are associated with low levels of plasma LDL
      cholesterol and a reduced risk of coronary heart disease. PCSK9 gain-of-function
      mutations result in lower LDL clearance and increased risk of atherosclerosis.
      The exact mechanism by which PCSK9 disrupts the normal recycling of LDLR remains
      to be determined. In this study, we have assembled homologs of human PCSK9 from
      20 vertebrates, a cephalochordate and mollusks in order to search for conserved
      regions of PCSK9 that may be important for the PCSK9-mediated degradation of
      LDLR. We found a large, conserved protrusion on the surface of the PCSK9
      catalytic domain and have performed site-directed mutagenesis experiments for 13
      residues on this protrusion. A cluster of residues that is important for the
      degradation of LDLR by PCSK9 was identified. Another cluster of residues, at the
      opposite end of the conserved protrusion, appears to be involved in the physical
      interaction with a putative inhibitor of PCSK9. This study identifies the
      residues, sequence segments and surface patches of PCSK9 that are under strong
      purifying selection and provides important information for future studies of
      PCSK9 mutants and for investigations on the function of this regulator of
      cholesterol homeostasis.

PMID- 18631361
TI  - Nop53p interacts with 5.8S rRNA co-transcriptionally, and regulates processing of
      pre-rRNA by the exosome.
AB  - In eukaryotes, pre-rRNA processing depends on a large number of nonribosomal
      trans-acting factors that form intriguingly organized complexes. One of the early
      stages of pre-rRNA processing includes formation of the two intermediate
      complexes pre-40S and pre-60S, which then form the mature ribosome subunits. Each
      of these complexes contains specific pre-rRNAs, ribosomal proteins and processing
      factors. The yeast nucleolar protein Nop53p has previously been identified in the
      pre-60S complex and shown to affect pre-rRNA processing by directly binding to
      5.8S rRNA, and to interact with Nop17p and Nip7p, which are also involved in this
      process. Here we show that Nop53p binds 5.8S rRNA co-transcriptionally through
      its N-terminal region, and that this protein portion can also partially
      complement growth of the conditional mutant strain Deltanop53/GAL::NOP53. Nop53p
      interacts with Rrp6p and activates the exosome in vitro. These results indicate
      that Nop53p may recruit the exosome to 7S pre-rRNA for processing. Consistent
      with this observation and similar to the observed in exosome mutants, depletion
      of Nop53p leads to accumulation of polyadenylated pre-rRNAs.

PMID- 18631362
TI  - Development and evaluation of a quantitative real-time PCR assay for the
      detection of saltwater Bacteriovorax.
AB  - Bdellovibrio-and-like-organisms (BALOs) are small, Gram-negative predatory
      bacteria with the ability to prey on a wide variety of Gram-negative bacteria,
      and which may have a significant ecological role. Detection and quantification of
      BALOs by culture-dependent methods are complicated, as their reproduction is
      dependent upon the use of appropriate prey. For this reason, a sensitive and
      specific molecular detection method was developed. This paper describes a SYBR
      Green-based real-time PCR (quantitative PCR) assay that combines the use of a
      specific 16S rDNA primer with a universal primer for quantitative detection of
      halophilic Bacteriovorax. 16S rDNA sequences from 174 BALO strains, including
      both halophilic and freshwater, were aligned and a consensus region was
      identified that is unique to the halophilic Bacteriovorax strains. A specific
      primer was designed and analysed for specificity. The PCR conditions were
      optimized to obtain high specificity and sensitivity. The specificity was
      evaluated by testing a series of halophilic Bacteriovorax samples and prey
      specimens, including both pure cultures and environmental saltwater samples. A
      linear and reproducible standard curve was obtained over a range of 10(1)-10(6)
      gene copies and the detection limit was determined to be 10 copies of 16S rRNA
      gene per reaction. The results presented in this study validate the procedure as
      a rapid, sensitive and accurate method for the detection and quantification of
      halophilic Bacteriovorax in environmental saltwater samples. It is anticipated
      that this culture-independent method will facilitate future investigations of the
      distribution and population dynamics of these interesting predatory bacteria,
      leading to a better understanding of their ecological role.

PMID- 18631363
TI  - Enriching plant microbiota for a metagenomic library construction.
AB  - Plant microbiota (the microorganisms that live in any associations with plant
      tissues) represents a rather unexplored area of metagenomic research compared
      with soils and oceans. Constructing a metagenomic library for plant microbiota is
      technically challenging. Using all the biomass without pre-enrichment could lead
      to vast proportions of the host plant DNA in the metagenomic library, doubtless
      obliterating the microbial contribution. Therefore, the first and essential step
      is to enrich for the constituent microorganisms from plant tissues. Here, a
      strong enrichment for plant microbiota was achieved by coupling SDS (sodium
      dodecyl sulfate) with NaCl, creating a predominantly microbial metagenomic
      library that contains 88% bacterial inserts. 16S rDNA sequence analysis revealed
      that the metagenomic DNA of enrichments originates from very diverse
      microorganisms. At least 74 distinct ribotypes (at a 97% threshold) from seven
      different bacterial phyla were identified and mainly distributed among
      Actinobacteria and Proteobacteria. Additionally, a simplified version of
      Amplified Ribosomal DNA Restriction Analysis (ARDRA) was developed for a quick
      and efficient assessment of the enriching procedures. This work opens further
      insight into the great biotechnical potential of plant microbiota, holding more
      potential for drug discovery through a metagenomic strategy, and paving the way
      for recovery and biochemical characterization of functional gene repertoire from
      plant microbiota.

PMID- 18631364
TI  - Revealing the uncultivated majority: combining DNA stable-isotope probing,
      multiple displacement amplification and metagenomic analyses of uncultivated
      Methylocystis in acidic peatlands.
AB  - Peatlands represent an enormous carbon reservoir and have a potential impact on
      the global climate because of the active methanogenesis and methanotrophy in
      these soils. Uncultivated methanotrophs from seven European peatlands were
      studied using a combination of molecular methods. Screening for methanotroph
      diversity using a particulate methane monooxygenase-based diagnostic gene array
      revealed that Methylocystis-related species were dominant in six of the seven
      peatlands studied. The abundance and methane oxidation activity of Methylocystis
      spp. were further confirmed by DNA stable-isotope probing analysis of a sample
      taken from the Moor House peatland (England). After ultracentrifugation, (13)C
      labelled DNA, containing genomic DNA of these Methylocystis spp., was separated
      from (12)C DNA and subjected to multiple displacement amplification (MDA) to
      generate sufficient DNA for the preparation of a fosmid metagenomic library.
      Potential bias of MDA was detected by fingerprint analysis of 16S rRNA using
      denaturing gradient gel electrophoresis for low-template amplification (0.01 ng
      template). Sufficient template (1-5 ng) was used in MDA to circumvent this bias
      and chimeric artefacts were minimized by using an enzymatic treatment of MDA
      generated DNA with S1 nuclease and DNA polymerase I. Screening of the metagenomic
      library revealed one fosmid containing methanol dehydrogenase and two fosmids
      containing 16S rRNA genes from these Methylocystis-related species as well as one
      fosmid containing a 16S rRNA gene related to that of Methylocella/Methylocapsa.
      Sequencing of the 14 kb methanol dehydrogenase-containing fosmid allowed the
      assembly of a gene cluster encoding polypeptides involved in bacterial methanol
      utilization (mxaFJGIRSAC). This combination of DNA stable-isotope probing, MDA
      and metagenomics provided access to genomic information of a relatively large DNA
      fragment of these thus far uncultivated, predominant and active methanotrophs in
      peatland soil.

PMID- 18631366
TI  - Electroencephalographic evolution of hypsarrhythmia: toward an early treatment
      option.
AB  - PURPOSE: A retrospective study for a classification of prehypsarrhythmic
      elecroencephalographies (EEGs) was carried out to enable an early treatment
      option for West syndrome. METHODS: Out of 39 infants with symptomatic West
      syndrome, 18 infants (age 3-14 months) with 61 serial non-REM sleep EEG records
      of the prehypsarrhythmic phase were identified. The prehypsarrhythmic phase
      encompassed 2 to 13 months (mean 4.5 months) after an initial insult. A
      classification system of three EEG types corresponding to the clinical states
      prior to West syndrome occurrence was developed. In addition, follow-up of all
      patients presenting with type 2 EEGs (n = 22) was evaluated. RESULTS: Three
      clinical states and corresponding EEG types were classified. Clinical state 1
      (weeks to months, silent phase) presented with (multi-)focal epileptic discharges
      <50% of the non-REM EEG recording time (type 1 EEG). Clinical state 2 (several
      weeks, beginning mental deterioration) was accompanied by type 2 EEG with
      bihemispheric epileptic discharges >50% of the non-REM EEG recording time within
      abnormal background activity (imminent hypsarrhythmia). Clinical state 3 (mental
      deterioration) was characterized by hypsarryhthmia. Interrater reliability of
      seven blinded raters was good (median weighted kappa 0.67). Out of 22 patients
      presenting with type 2 EEGs, two were lost for follow-up, and 16 developed West
      syndrome, whereas four were treated early with anti-epileptic drugs and remained
      stable. CONCLUSIONS: Infants with West syndrome could be reliably identified
      several weeks before the occurrence of hypsarrhythmia by a typical EEG pattern
      (type 2), thereby opening the way for early intervention studies.

PMID- 18631365
TI  - The complete genome sequence of Moorella thermoacetica (f. Clostridium
      thermoaceticum).
AB  - This paper describes the genome sequence of Moorella thermoacetica (f.
      Clostridium thermoaceticum), which is the model acetogenic bacterium that has
      been widely used for elucidating the Wood-Ljungdahl pathway of CO and CO(2)
      fixation. This pathway, which is also known as the reductive acetyl-CoA pathway,
      allows acetogenic (often called homoacetogenic) bacteria to convert glucose
      stoichiometrically into 3 mol of acetate and to grow autotrophically using H(2)
      and CO as electron donors and CO(2) as an electron acceptor. Methanogenic archaea
      use this pathway in reverse to grow by converting acetate into methane and CO(2).
      Acetogenic bacteria also couple the Wood-Ljungdahl pathway to a variety of other
      pathways to allow the metabolism of a wide variety of carbon sources and electron
      donors (sugars, carboxylic acids, alcohols and aromatic compounds) and electron
      acceptors (CO(2), nitrate, nitrite, thiosulfate, dimethylsulfoxide and aromatic
      carboxyl groups). The genome consists of a single circular 2 628 784 bp
      chromosome encoding 2615 open reading frames (ORFs), which includes 2523
      predicted protein-encoding genes. Of these, 1834 genes (70.13%) have been
      assigned tentative functions, 665 (25.43%) matched genes of unknown function, and
      the remaining 24 (0.92%) had no database match. A total of 2384 (91.17%) of the
      ORFs in the M. thermoacetica genome can be grouped in orthologue clusters. This
      first genome sequence of an acetogenic bacterium provides important information
      related to how acetogens engage their extreme metabolic diversity by switching
      among different carbon substrates and electron donors/acceptors and how they
      conserve energy by anaerobic respiration. Our genome analysis indicates that the
      key genetic trait for homoacetogenesis is the core acs gene cluster of the Wood
      Ljungdahl pathway.

PMID- 18631367
TI  - NIRS-measured oxy- and deoxyhemoglobin changes associated with EEG spike-and-wave
      discharges in children.
AB  - PURPOSE: Absence epilepsy is characterized by 3-Hz generalized spike-and-wave
      discharges (GSWD) on the electroencephalogram, associated with behavioral arrest.
      It may be severe, and even in childhood benign absence epilepsy cognitive delay
      is frequent, yet the metabolic/hemodynamic aspects of this kind of epilepsy have
      not been established. We aimed to determine if the GSWD were related to
      hemodynamic changes by using a new technique with high temporal resolution: near
      infrared spectroscopy (NIRS). METHODS: NIRS is gaining acceptance as a technique
      particularly suitable for routine follow-up in children, using the specific
      absorption properties of living tissues in the near infrared range to measure
      changes in the concentrations of oxy-, deoxy- and total hemoglobin (HbO(2), HHb,
      and HbT, respectively). We performed simultaneous electroencephalography (EEG)
      and left frontal NIRS recordings in six children with GSWD. We also tested if the
      discharges were related to changes in cardiac or respiratory rates. RESULTS: GSWD
      were associated in the frontal area with an oxygenation (beginning 10 s before
      the GSWD) followed by strong deoxygenation, then oxygenation again with [HbT]
      increase, and a return to baseline. We did not identify any relationship between
      the onset of the GSWD and heart or respiratory rates. DISCUSSION: Our results
      partially differ from previous studies on GSWD hemodynamic aspects (many of which
      described a simple deactivation), probably due to differences in temporal
      resolution and data processing. Simultaneous acquisition of EEG and NIRS can
      optimize the use of both techniques and help shed light on the mechanisms
      underlying spike-and-wave discharges.

PMID- 18631368
TI  - Combination of capillary electrophoresis, PCR and physiological assays in
      differentiation of clinical strains of Staphylococcus aureus.
AB  - Fast, sensitive and cheap determination of pathogenic bacteria is extremely
      important in many branches, for example biotechnology, quality control, analysis
      of samples and antimicrobial therapy. The development and application of
      analytical techniques in practice could provide new possibilities in this regard.
      The bacterial pathogen Staphylococcus aureus is responsible for a significant
      amount of human morbidity and mortality. Rapid and sensitive determination is
      therefore very important. In the present study, novel methods, based on capillary
      zone electrophoresis and (as confirmation of these results) molecular analysis of
      a part of the coag gene, were developed for identification and differentiation of
      three S. aureus strains. The electrophoretic measurements rely on the
      differential mobility of bacteria in the fused silica capillary under the direct
      current electric field. To perform coagulase gene typing, the repeated units
      encoding hypervariable regions of the S. aureus gene were amplified using the PCR
      technique followed by restriction enzyme digestion and analysis of restriction
      fragment length polymorphism patterns as well as sequencing. Finally, the results
      of electrophoretic measurements with molecular analysis were compared.

PMID- 18631369
TI  - Bacterial infection changes the elemental composition of Daphnia magna.
AB  - 1. An animal's elemental composition can be an important indicator of its
      physiological state and role in ecosystem nutrient cycling. We examined the
      interactive effects of bacterial (Pasteuria ramosa) infection and phosphorus (P)
      poor food on the body stoichiometry of Daphnia magna. Daphnia were exposed to or
      held free of a bacterial parasite and fed algal food of different C:P ratios (100
      500) over a 28-day period. 2. To assess the effects of exposure and infection on
      Daphnia stoichiometry, we measured their whole body content of carbon (C),
      nitrogen (N), and P on four different days (4, 8, 15, and 28) during the
      experiment. 3. We found strong effects of infection, food quality, and/or their
      interactions on the C, N, and P content of Daphnia, especially as the infectious
      disease progressed. At the end of the experiment, infected animals had
      significantly more C and less P in their bodies than uninfected conspecifics.
      Body N content of Daphnia consuming P-rich food was reduced by bacterial
      infection whereas Daphnia consuming P-poor algae showed increased body N content
      from infection. 4. Using a mass-balance model, we found that changes in N and P
      content of host bodies were largely accountable by disease-induced alterations to
      Daphnia reproduction (i.e. bacterial induced sterility) and the accumulation of
      Pasteuria spores in the body cavity. Our calculations also show that the observed
      increase in host C content could not be accounted for by loss of eggs or
      accumulation of bacterial spores. This instead must result from unidentified
      changes to underlying daphnid tissue C content. 5. These results demonstrate that
      intraspecific variation in zooplankton body stoichiometry can be caused by
      exposure to and infection by bacterial parasites. In addition, these effects were
      found to depend both upon the stage of the disease and upon the food quality
      consumed by the host.

PMID- 18631370
TI  - Using likelihood to test for Levy flight search patterns and for general power
      law distributions in nature.
AB  - 1. Ecologists are obtaining ever-increasing amounts of data concerning animal
      movement. A movement strategy that has been concluded for a broad variety of
      animals is that of Levy flights, which are random walks whose step lengths come
      from probability distributions with heavy power-law tails. 2. The exponent that
      parameterizes the power-law tail, denoted micro, has repeatedly been found to be
      within the Levy range of 1 < micro <or= 3. Here, we use Monte Carlo simulations
      to show that the methods used to infer the value of micro are inaccurate. 3. The
      widely used method of simply logarithmically transforming a standard histogram of
      movement lengths has been shown elsewhere to be problematic. Here, we further
      demonstrate how poor it is, and show that it actually biases estimates of micro
      towards the Levy range of 1 < micro <or= 3, and can bias estimates towards the
      value of micro = 2. Thus, previous reports of animals undergoing Levy flights, or
      of micro being close to the reported optimal value of micro = 2, may simply be a
      consequence of the bias generated by this method. 4. A technique that has been
      recently recommended is to logarithmically bin the data and then normalize the
      resulting histogram. We show that this technique also produces biased results,
      and suffers from similar problems as those just outlined, although to a lesser
      extent. 5. The proposed solution is to use likelihood. We find that calculating
      the maximum likelihood estimate of micro gives the most accurate results (having
      also tested the rank/frequency method). Likelihood has the further advantages of
      being the easiest method to implement, and of yielding accurate confidence
      intervals. Results are applicable to power-law distributions in general, and so
      are not restricted to inference of Levy flights. 6. We also re-analyse a data set
      of grey seal movements that was originally reported to demonstrate Levy flight
      behaviour. Using Akaike weights, we test four models, and find no evidence for
      Levy flights. Overall, our results suggest that Levy flights might not be as
      common as previously thought.

PMID- 18631372
TI  - Chiral N-phosphonyl imine chemistry: asymmetric additions of ester enolates for
      the synthesis of beta-amino acids.
AB  - Chiral phosphonyl imines attached by 1-naphthyl protection group were found to
      react with lithium ester enolates smoothly and give chiral beta-amino esters in
      good yields (70-88%) and up to excellent diastereoselectivity (>99:1 dr).
      Triisopropoxytitanium (IV) chloride was found to enhance diastereoseletivity when
      used as the Lewis acid promoter. The chiral auxiliary can be readily removed by
      treating with HBr to give free amino esters. The absolute structure has been
      unambiguously determined by converting one of the products into an authentic
      sample. This reaction provides an easy access to beta-amino acid derivatives.

PMID- 18631371
TI  - Endoplasmic reticulum stress is involved in hydrogen peroxide induced apoptosis
      in immortalized and malignant human oral keratinocytes.
AB  - BACKGROUND: Although hydrogen peroxide may play an important role in the
      development of cancer, it can be an efficient inducer of apoptosis in cancer
      cells; the exact mechanism by which this action occurs is not completely
      understood in oral cancer cells. METHOD: In this study, the mechanisms by which
      H(2)O(2) inhibited growth and induced apoptosis were differentially investigated
      using HPV-immortalized human oral keratinocytes (IHOK) and oral cancer cells
      (HN4). RESULTS: H(2)O(2) treatment sensitively and dose-dependently induced
      growth inhibition and typical apoptosis in IHOK and HN4 cells, as demonstrated by
      a decreased level of cell viability, an increased population of cells in the sub
      G(0)/G(1) phase, ladder formation of the genomic DNA, chromatin condensation and
      accumulation of Annexin V(+)/PI(+) cells. Furthermore, the expression of Bax, p53
      and p21(WAF1/CIP1) increased, whereas the expression of Bcl-2 decreased in
      immortalized and malignant keratinocytes that were treated with H(2)O(2). In
      addition, cytochrome-c from the mitochondria was observed in H(2)O(2)-treated
      IHOK and oral cancer cells, and this was accompanied by the activation of caspase
      3 and -9. Additionally, H(2)O(2) treatment induced upregulation of CHOP, GRP78
      and several representative endoplasmic reticulum (ER) stress-responsive proteins,
      including heme oxygenase-1. CONCLUSION: Overall, these results suggest that
      H(2)O(2) triggers apoptosis via the mitochondrial and ER stress pathway in IHOK
      and HN4 cells, and that increasing the cellular levels of H(2)O(2) sufficiently
      may lead to selective killing of oral cancer cells and therefore be
      therapeutically useful.

PMID- 18631373
TI  - Enzyme phylogenies as markers for the oxidation state of the environment: the
      case of respiratory arsenate reductase and related enzymes.
AB  - BACKGROUND: Phylogenies of certain bioenergetic enzymes have proved to be useful
      tools for deducing evolutionary ancestry of bioenergetic pathways and their
      relationship to geochemical parameters of the environment. Our previous
      phylogenetic analysis of arsenite oxidase, the molybdopterin enzyme responsible
      for the biological oxidation of arsenite to arsenate, indicated its probable
      emergence prior to the Archaea/Bacteria split more than 3 billion years ago, in
      line with the geochemical fact that arsenite was present in biological habitats
      on the early Earth. Respiratory arsenate reductase (Arr), another molybdopterin
      enzyme involved in microbial arsenic metabolism, serves as terminal oxidase, and
      is thus situated at the opposite end of bioenergetic electron transfer chains as
      compared to arsenite oxidase. The evolutionary history of the Arr-enzyme has not
      been studied in detail so far. RESULTS: We performed a genomic search of genes
      related to arrA coding for the molybdopterin subunit. The multiple alignment of
      the retrieved sequences served to reconstruct a neighbor-joining phylogeny of Arr
      and closely related enzymes. Our analysis confirmed the previously proposed
      proximity of Arr to the cluster of polysulfide/thiosulfate reductases but also
      unravels a hitherto unrecognized clade even more closely related to Arr. The
      obtained phylogeny strongly suggests that Arr originated after the
      Bacteria/Archaea divergence in the domain Bacteria, and was subsequently
      laterally distributed within this domain. It further more indicates that, as a
      result of accumulation of arsenate in the environment, an enzyme related to
      polysulfide reductase and not to arsenite oxidase has evolved into Arr.
      CONCLUSION: These findings are paleogeochemically rationalized by the fact that
      the accumulation of arsenate over arsenite required the increase in oxidation
      state of the environment brought about by oxygenic photosynthesis.

PMID- 18631374
TI  - Psychosocial risk factors in home and community settings and their associations
      with population health and health inequalities: a systematic meta-review.
AB  - BACKGROUND: The effects of psychosocial risk factors on population health and
      health inequalities has featured prominently in epidemiological research
      literature as well as public health policy strategies. We have conducted a meta
      review (a review of reviews) exploring how psychosocial factors may relate to
      population health in home and community settings. METHODS: Systematic review
      (QUORUM) of literature reviews (published in any language or country) on the
      health associations of psychosocial risk factors in community settings. The
      literature search included electronic and manual searches. Two reviewers
      appraised included reviews using criteria for assessing systematic reviews. Data
      from the more robust reviews were extracted, tabulated and synthesised. RESULTS:
      Thirty-one reviews met our inclusion criteria. These explored a variety of
      psychosocial factors including social support and networks, social capital,
      social cohesion, collective efficacy, participation in local organisations - and
      less favourable psychosocial risk factors such as demands, exposure to community
      violence or anti-social behaviour, exposure to discrimination, and stress related
      to acculturation to western society. Most of the reviews focused on associations
      between social networks/support and physical or mental health. We identified some
      evidence of favourable psychosocial environments associated with better health.
      Reviews also found evidence of unfavourable psychosocial risk factors linked to
      poorer health, particularly among socially disadvantaged groups. However, the
      more robust reviews each identified studies with inconclusive findings, as well
      as studies finding evidence of associations. We also identified some evidence of
      apparently favourable psychosocial risk factors associated with poorer health.
      CONCLUSION: From the review literature we have synthesised, where associations
      have been identified, they generally support the view that favourable
      psychosocial environments go hand in hand with better health. Poor psychosocial
      environments may be health damaging and contribute to health inequalities. The
      evidence that underpins our understanding of these associations is of variable
      quality and consistency. Future research should seek to improve this evidence
      base, with more longitudinal analysis (and intervention evaluations) of the
      effects of apparently under-researched psychosocial factors such as control and
      participation within communities. Future policy interventions relevant to this
      field should be developed in partnership with researchers to enable a better
      understanding of psychosocial mechanisms and the effects of psychosocial
      interventions.

PMID- 18631375
TI  - Comparison of functional residual capacity and static compliance of the
      respiratory system during a positive end-expiratory pressure (PEEP) ramp
      procedure in an experimental model of acute respiratory distress syndrome.
AB  - INTRODUCTION: Functional residual capacity (FRC) measurement is now available on
      new ventilators as an automated procedure. We compared FRC, static
      thoracopulmonary compliance (Crs) and PaO2 evolution in an experimental model of
      acute respiratory distress syndrome (ARDS) during a reversed, sequential ramp
      procedure of positive end-expiratory pressure (PEEP) changes to investigate the
      potential interest of combined FRC and Crs measurement in such a pathologic
      state. METHODS: ARDS was induced by oleic acid injection in six anesthetised
      pigs. FRC and Crs were measured, and arterial blood samples were taken after
      induction of ARDS during a sequential ramp change of PEEP from 20 cm H2O to 0 cm
      H2O by steps of 5 cm H2O. RESULTS: ARDS was responsible for significant decreases
      in FRC, Crs and PaO2 values. During ARDS, 20 cm H2O of PEEP was associated with
      FRC values that increased from 6.2 +/- 1.3 to 19.7 +/- 2.9 ml/kg and a
      significant improvement in PaO2. The maximal value of Crs was reached at a PEEP
      of 15 cm H2O, and the maximal value of FRC at a PEEP of 20 cm H2O. From a PEEP
      value of 15 to 0 cm H2O, FRC and Crs decreased progressively. CONCLUSION: Our
      results indicate that combined FRC and Crs measurements may help to identify the
      optimal level of PEEP. Indeed, by taking into account the value of both
      parameters during a sequential ramp change of PEEP from 20 cm H2O to 0 cm H2O by
      steps of 5 cm H2O, the end of overdistension may be identified by an increase in
      Crs and the start of derecruitment by an abrupt decrease in FRC.

PMID- 18631376
TI  - Correlation between amino acid residues converted by RNA editing and functional
      residues in protein three-dimensional structures in plant organelles.
AB  - BACKGROUND: In plant organelles, specific messenger RNAs (mRNAs) are subjected to
      conversion editing, a process that often converts the first or second nucleotide
      of a codon and hence the encoded amino acid. No systematic patterns in converted
      sites were found on mRNAs, and the converted sites rarely encoded residues
      located at the active sites of proteins. The role and origin of RNA editing in
      plant organelles remain to be elucidated. RESULTS: Here we study the relationship
      between amino acid residues encoded by edited codons and the structural
      characteristics of these residues within proteins, e.g., in protein-protein
      interfaces, elements of secondary structure, or protein structural cores. We find
      that the residues encoded by edited codons are significantly biased toward
      involvement in helices and protein structural cores. RNA editing can convert
      codons for hydrophilic to hydrophobic amino acids. Hence, only the edited form of
      an mRNA can be translated into a polypeptide with helix-preferring and core
      forming residues at the appropriate positions, which is often required for a
      protein to form a functional three-dimensional (3D) structure. CONCLUSION: We
      have performed a novel analysis of the location of residues affected by RNA
      editing in proteins in plant organelles. This study documents that RNA editing
      sites are often found in positions important for 3D structure formation. Without
      RNA editing, protein folding will not occur properly, thus affecting gene
      expression. We suggest that RNA editing may have conferring evolutionary
      advantage by acting as a mechanism to reduce susceptibility to DNA damage by
      allowing the increase in GC content in DNA while maintaining RNA codons essential
      to encode residues required for protein folding and activity.

PMID- 18631377
TI  - Presumptive treatment of fever cases as malaria: help or hindrance for malaria
      control?
AB  - BACKGROUND: Malaria incidence has been reported to be falling in several
      countries in sub-Saharan Africa in recent years. This fall appears to have
      started before the widespread introduction of insecticide-treated nets. In the
      new era of calls to eliminate and eradicate malaria in sub-Saharan Africa,
      exploring possible causes for this fall seem pertinent. PRESENTATION OF THE
      HYPOTHESIS: The authors explore an argument that presumptive treatment of fever
      cases as malaria may have played a role in reducing transmission of malaria by
      the prophylactic effect of antimalarials and their widespread use. This strategy,
      which is already in practise is termed Opportunistic Presumptive Treatment (OPT).
      TESTING THE HYPOTHESIS: Further comparison of epidemiological indicators between
      areas with OPT and more targeted treatment is required. If data suggest a benefit
      of OPT, combining long acting antimalarials that have an anti-gametocyticidal
      activity component plus using high levels of vector control measures may reduce
      transmission, prevent resistant strains spreading and be easily implemented.
      IMPLICATIONS OF THE HYPOTHESIS: OPT is practised widely by presumptive treatment
      of fever in health facilities and home management of fever. Improving diagnosis
      using rapid diagnostic tests and thus reducing the number of doses of
      antimalarials given may have counter intuitive effects on transmission in the
      context of elimination of malaria in high to moderate transmission settings.

PMID- 18631378
TI  - Using deliberative techniques to engage the community in policy development.
AB  - BACKGROUND: This paper examines work in deliberative approaches to community
      engagement used in Western Australia by the Department of Planning and
      Infrastructure and other planning and infrastructure agencies between 2001 and
      2005, and considers whether the techniques could be applied to the development of
      health policy in Australia. RESULTS: Deliberative processes were used in WA to
      address specific planning and infrastructure problems. Using deliberative
      techniques, community participants contributed to joint decision making and
      policy development. Outcomes from deliberative processes were seriously
      considered by the Minister and used to influence policy decisions. In many cases,
      the recommendations generated through deliberative processes were fully adopted
      by the Minister. CONCLUSION: The experiences in WA demonstrate that deliberative
      engagement processes can be successfully implemented by government and can be
      used to guide policy. The techniques can be adapted to suit the context and
      issues experienced by a portfolio, and the skills required to conduct
      deliberative processes can be fostered amongst the portfolio's staff. Health
      policy makers may be able to learn from the experiences in WA, and adopt
      approaches to community engagement that allow for informed deliberation and
      debate in the community about the future of Australia's health system.

PMID- 18631380
TI  - A biomechanical study of plate versus intramedullary devices for midshaft
      clavicle fixation.
AB  - BACKGROUND: Non-operative management of midshaft clavicle fractures is standard;
      however, surgical management is increasing. The purpose of this study is to
      compare the biomechanical performance of plate versus intramedullary fixation in
      cyclic bending for matched pairs of cadaveric clavicles. We hypothesized that the
      biomechanical properties are similar. METHODS: Eight sets of matched clavicles
      with vertical, midshaft osteotomies were prepared from fresh, frozen cadavers. A
      3.5 mm dynamic compression plate or a 3.8 or 4.5 mm intramedullary device were
      used for fixation. Clavicles were loaded in a four-point bend at 6 different
      loads for 3000 cycles at 1 Hz starting with 180 N and increasing by 180 N with
      sampling at 2 Hz. Failure was defined as 10 mm of displacement or catastrophic
      construct failure prior to 10 mm of displacement. RESULTS: Between constructs,
      there was a significant difference with large effect size in displacement at
      fixed loads of 180 N (P = 0.001; Cohen's d = 1.85), 360 N (P = 0.033; Cohen's d =
      1.39), 540 N (P = 0.003; Cohen's d = 0.73) and 720 N (P = 0.018; Cohen's d =
      0.72). There was a significant difference with large effect size in load at fixed
      displacements of 5 mm (P = 0.001; Cohen's d = 1.49), 7.5 mm (P = 0.011; Cohen's d
      = 1.06), and 10 mm (P = 0.026; Cohen's d = 0.84). CONCLUSION: Plate constructs
      are superior in showing less displacement at fixed loads and greater loads at
      fixed displacements over a broad range of loads and displacements with cyclic
      four-point bending. The clinical relevance is that plate fixation may provide a
      stronger construct for early rehabilitation protocols that focus on repetitive
      movements in the early pre-operative period.

PMID- 18631379
TI  - The transcriptional program underlying the physiology of clostridial sporulation.
AB  - BACKGROUND: Clostridia are ancient soil organisms of major importance to human
      and animal health and physiology, cellulose degradation, and the production of
      biofuels from renewable resources. Elucidation of their sporulation program is
      critical for understanding important clostridial programs pertaining to their
      physiology and their industrial or environmental applications. RESULTS: Using a
      sensitive DNA-microarray platform and 25 sampling timepoints, we reveal the
      genome-scale transcriptional basis of the Clostridium acetobutylicum sporulation
      program carried deep into stationary phase. A significant fraction of the genes
      displayed temporal expression in six distinct clusters of expression, which were
      analyzed with assistance from ontological classifications in order to illuminate
      all known physiological observations and differentiation stages of this
      industrial organism. The dynamic orchestration of all known sporulation sigma
      factors was investigated, whereby in addition to their transcriptional profiles,
      both in terms of intensity and differential expression, their activity was
      assessed by the average transcriptional patterns of putative canonical genes of
      their regulon. All sigma factors of unknown function were investigated by
      combining transcriptional data with predicted promoter binding motifs and
      antisense-RNA downregulation to provide a preliminary assessment of their roles
      in sporulation. Downregulation of two of these sigma factors, CAC1766 and
      CAP0167, affected the developmental process of sporulation and are apparently
      novel sporulation-related sigma factors. CONCLUSION: This is the first detailed
      roadmap of clostridial sporulation, the most detailed transcriptional study ever
      reported for a strict anaerobe and endospore former, and the first reported
      holistic effort to illuminate cellular physiology and differentiation of a lesser
      known organism.

PMID- 18631381
TI  - BRAFV600E mutations in malignant melanoma are associated with increased
      expressions of BAALC.
AB  - BACHGROUND: Activating BRAF mutations are present in approximately 50% of
      melanomas. Although different downstream target genes of the most common mutant
      V600E have been identified, the contribution of activating BRAF mutations to
      malignant transformation needs further clarification. METHODS: Microarray gene
      analysis was performed for human melanoma cell lines harboring BRAFV600E
      mutations in comparison to cell lines without this mutation. RESULTS: This
      analysis revealed a more than two fold down-regulation of 43 and an increase of
      39 gene products. BAALC (Brain and acute Leukaemia, cytoplasmatic) was most
      prominently regulated, since it was up-regulated in mutated cell lines by a mean
      of 11.45. Real time PCR analyses with RNA from melanoma cell lines (n = 30)
      confirmed the BRAF-activation dependent up-regulation of BAALC. CONCLUSION:
      BAALC, which has been associated with cell dedifferentiation and migration, may
      function as a downstream effector of activating BRAF mutations during
      melanomagenesis.

PMID- 18631382
TI  - Lot quality survey: an appealing method for rapid evaluation of vaccine coverage
      in developing countries - experience in Turkey.
AB  - BACKGROUND: Vaccine-preventable diseases cause significant morbidity and
      mortality worldwide and in developing countries in particular. Information on
      coverage and reasons for non-vaccination is vital to enhance overall vaccination
      activities. Of the several survey techniques available for investigating
      vaccination coverage in a given setting, the Lot Quality Technique (LQT) remains
      appealing and could be used in developing countries by local health personnel of
      district or rural health authorities to evaluate their performance in vaccination
      and many other health-related programs. This study aimed to evaluate vaccination
      coverage using LQT in a selected semi-urban setting in Turkey. METHODS: A LQT
      based cross-sectional study was conducted in Kecioren District on a
      representative sample of residents aged 12-23 months in order to evaluate
      coverage for routine childhood vaccines, to identify health units with coverage
      below 75%, and to investigate reasons for non-vaccination. RESULTS: Based on self
      reports, coverage for BCG, diphtheria-pertussis-tetanus (DPT-3), oral polio-3,
      hepatitis-3, and measles vaccines ranged between 94-99%. Coverage for measles was
      below 75% in five lots. The relatively high educational and socioeconomic status
      of parents in the study group alone could not minimize the "considerable" risk of
      vaccine-preventable diseases in the District and dictates a continuity of efforts
      for improving vaccination rates, with special emphasis on measles. We believe
      that administrative methods should be backed up by household surveys to
      strengthen vaccination monitoring and that families should be trained and
      motivated to have their children fully vaccinated according to the recommended
      schedule and in a timely manner. CONCLUSION: This study identified vaccine
      coverage for seven routine vaccines completed before the age of 24 months as well
      as the areas requiring special attention in vaccination services. The LQT, years
      after its introduction to health-related research, remains an appealing technique
      for rapid evaluation of the extent of a variety of local health concerns in
      developing countries, in rural areas in particular, and is very efficient in
      determining performance of individual subunits in a given service area. Training
      of local health personnel on use of the LQT could expedite response to local
      health problems and could even motivate them in conducting their own surveys
      tailored to their professional interests.

PMID- 18631383
TI  - More cases, doctor? Yes please!

PMID- 18631384
TI  - Rehabilitation of a congenital palatal defect with a modified technique: a case
      report.
AB  - INTRODUCTION: Constuction of the obturator prostheses and providing the patient's
      comfort with them are very difficult. Primary and the most important stage for
      these prostheses is to perform a proper impression. CASE PRESENTATION: A 55-year
      old edentulous Turkish female patient with a congenitally maxillary defect was
      rehabilitated with an open hollow obturator prosthesis. After the preliminary
      impression was completed, a metal frame suitable with the maxillary defect was
      constructed manually and used for making the impression of the defect area. After
      the first part of the obturator was finished, second part which separates nasal
      cavity and oral cavity was constructed by the aid of the bulb. CONCLUSION: When
      constructing an obturator prosthesis, making a detailed impression from the
      defect area can be performed by the aid of a metal frame, and an intraorally
      shaped extension that separates oral cavity from nasal cavity might be more
      effective for adaptation of the prosthesis.

PMID- 18631385
TI  - PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic
      plasticity and behavior.
AB  - The laterocapsular division of the central nucleus of the amygdala (CeLC) has
      emerged as an important site of pain-related plasticity and pain modulation.
      Glutamate and neuropeptide receptors in the CeLC contribute to synaptic and
      behavioral changes in the arthritis pain model, but the intracellular signaling
      pathways remain to be determined. This study addressed the role of PKA, PKC, and
      ERK in the CeLC. Adult male Sprague-Dawley rats were used in all experiments.
      Whole-cell patch-clamp recordings of CeLC neurons were made in brain slices from
      normal rats and from rats with a kaolin/carrageenan-induced monoarthritis in the
      knee (6 h postinduction). Membrane-permeable inhibitors of PKA (KT5720, 1 microM;
      cAMPS-Rp, 10 microM) and ERK (U0126, 1 microM) activation inhibited synaptic
      plasticity in slices from arthritic rats but had no effect on normal transmission
      in control slices. A PKC inhibitor (GF109203x, 1 microM) and an inactive
      structural analogue of U0126 (U0124, 1 microM) had no effect. The NMDA receptor
      mediated synaptic component was inhibited by KT5720 or U0126; their combined
      application had additive effects. U0126 did not inhibit synaptic facilitation by
      forskolin-induced PKA-activation. Administration of KT5720 (100 microM,
      concentration in microdialysis probe) or U0126 (100 microM) into the CeLC, but
      not striatum (placement control), inhibited audible and ultrasonic vocalizations
      and spinal reflexes of arthritic rats but had no effect in normal animals.
      GF109203x (100 microM) and U0124 (100 microM) did not affect pain behavior. The
      data suggest that in the amygdala PKA and ERK, but not PKC, contribute to pain
      related synaptic facilitation and behavior by increasing NMDA receptor function
      through independent signaling pathways.

PMID- 18631386
TI  - Healthcare professionals' intentions and behaviours: a systematic review of
      studies based on social cognitive theories.
AB  - BACKGROUND: There is an important gap between the implications of clinical
      research evidence and the routine clinical practice of healthcare professionals.
      Because individual decisions are often central to adoption of a clinical-related
      behaviour, more information about the cognitive mechanisms underlying behaviours
      is needed to improve behaviour change interventions targeting healthcare
      professionals. The aim of this study was to systematically review the published
      scientific literature about factors influencing health professionals' behaviours
      based on social cognitive theories. These theories refer to theories where
      individual cognitions/thoughts are viewed as processes intervening between
      observable stimuli and responses in real world situations. METHODS: We searched
      psycINFO, MEDLINE, EMBASE, CIHNAL, Index to theses, PROQUEST dissertations and
      theses and Current Contents for articles published in English only. We included
      studies that aimed to predict healthcare professionals' intentions and behaviours
      with a clear specification of relying on a social cognitive theory. Information
      on percent of explained variance (R(2)) was used to compute the overall frequency
      weighted mean R(2) to evaluate the efficacy of prediction in several contexts and
      according to different methodological aspects. The cognitive factors most
      consistently associated with prediction of healthcare professionals' intention
      and behaviours were documented. RESULTS: Seventy eight studies met the inclusion
      criteria. Among these studies, 72 provided information on the determinants of
      intention and 16 prospective studies provided information on the determinants of
      behaviour. The theory most often used as reference was the Theory of Reasoned
      Action (TRA) or its extension the Theory of Planned Behaviour (TPB). An overall
      frequency-weighted mean R(2) of 0.31 was observed for the prediction of
      behaviour; 0.59 for the prediction of intention. A number of moderators
      influenced the efficacy of prediction; frequency-weighted mean R(2) varied from
      0.001 to 0.58 for behaviour and 0.19 to 0.81 for intention. CONCLUSION: Our
      results suggest that the TPB appears to be an appropriate theory to predict
      behaviour whereas other theories better capture the dynamic underlying intention.
      In addition, given the variations in efficacy of prediction, special care should
      be given to methodological issues, especially to better define the context of
      behaviour performance.

PMID- 18631387
TI  - Non-protein coding RNA biomarkers and differential expression in cancers: a
      review.
AB  - BACKGROUND: In these years a huge number of human transcripts has been found that
      do not code for proteins, named non-protein coding RNAs. In most cases, small
      (miRNAs, snoRNAs) and long RNAs (antisense RNA, dsRNA, and long RNA species) have
      many roles, functioning as regulators of other mRNAs, at transcriptional and post
      transcriptional level, and controlling protein ubiquitination and degradation.
      Various species of npcRNAs have been found differentially expressed in different
      types of cancer. This review discusses the published data and new results on the
      expression of a subset of npcRNAs. CONCLUSION: These results underscore the
      complexity of the RNA world and provide further evidence on the involvement of
      functional RNAs in cancer cell growth control.

PMID- 18631388
TI  - Practice postcode versus patient population: a comparison of data sources in
      England and Scotland.
AB  - BACKGROUND: Health professionals, policy-makers and researchers need to be able
      to explore potential associations between prevalence rates and quality of care
      with a range of possible determinants including socio-economic deprivation and
      morbidity levels to determine the impact of commissioning and service delivery.
      In the UK, data in England are only available nationally at practice postcode
      level. In Scotland, such data are available based on an aggregate of the
      practices population's postcodes. The use of data assigned to the practice
      postcode may underestimate the association between ill health and income
      deprivation. Here, we report on the impact of using data assigned to the practice
      population by comparing analyses using English and Scottish data. RESULTS: Income
      deprivation based on data assigned to the practice postcode under-estimated
      deprivation compared to using income deprivation data assigned to the practice
      population for the five least deprived deciles, and over-estimated deprivation
      for the five most deprived deciles. The biggest differences were found for the
      most deprived decile. A similar trend was found for limiting long-term illness
      (LLTI). Differences between the QOF prevalence rates of the least and most
      deprived deciles using practice postcode data were similar (0.2% points or less)
      in England and Scotland for 8 out of 10 clinical domains. Using practice
      population assigned deprivation, differences in the prevalence rate between the
      least and most deprived deciles increase for all clinical domains. A similar
      trend was again found for LLTI. Using practice population assigned deprivation,
      differences for population achievement increase for all CHD quality indicators
      with the exception of beta-blockers (CHD10). With practice postcode assigned
      deprivation, significant differences between the least and most deprived deciles
      were found for 2 out 8 indicators, compared to 5 using practice population
      assigned deprivation. For LLTI differences between the lowest and most deprived
      deciles increased for all indicators when ill health assigned to the practice
      population was used. CONCLUSION: We have found, through comparing deprivation and
      ill health data assigned to either the practice postcode or the practice
      population postcode in Scotland, that analyses based on practice postcode
      assigned data under-estimated the relationship between deprivation and ill health
      for both prevalence and quality care. Given the importance of understanding the
      effect of deprivation and ill health on a range of determinants related to health
      care, policy makers should ensure that practice population data are available and
      used at national level in England and elsewhere where possible.

PMID- 18631389
TI  - Implementing the European guidelines for cardiovascular disease prevention in the
      primary care setting in Cyprus: lessons learned from a health care services
      study.
AB  - BACKGROUND: Recent guidelines recommend assessment and treatment of the overall
      risk for cardiovascular disease (CVD) through management of multiple risk factors
      in patients at high absolute risk. The aim of our study was to assess the level
      of cardiovascular risk in patients with known risk factors for CVD by applying
      the SCORE risk function and to study the implications of European guidelines on
      the use of treatment and goal attainment for blood pressure (BP) and lipids in
      the primary care of Cyprus. METHODS: Retrospective chart review of 1101 randomly
      selected patients with type 2 diabetes mellitus (DM2), or hypertension or
      hyperlipidemia in four primary care health centres. The SCORE risk function for
      high-risk regions was used to calculate 10-year risk of cardiovascular fatal
      event. Most recent values of BP and lipids were used to assess goal attainment to
      international standards. Most updated medications lists were used to compare
      proportions of current with recommended antihypertensive and lipid-lowering drug
      (LLD) users according to European guidelines. RESULTS: Implementation of the
      SCORE risk model labelled overall 39.7% (53.6% of men, 31.3% of women) of the
      study population as high risk individuals (CVD, DM2 or SCORE > or =5%). The SCORE
      risk chart was not applicable in 563 patients (51.1%) due to missing data in the
      patient records, mostly on smoking habits. The LDL-C goal was achieved in 28.6%,
      19.5% and 20.9% of patients with established CVD, DM2 (no CVD) and SCORE > or
      =5%, respectively. BP targets were achieved in 55.4%, 5.6% and 41.9% respectively
      for the above groups. There was under prescription of antihypertensive drugs, LLD
      and aspirin for all three high risk groups. CONCLUSION: This study demonstrated
      suboptimal control and under-treatment of patients with cardiovascular risk
      factors in the primary care in Cyprus. Improvement of documentation of clinical
      information in the medical records as well as GPs training for implementation and
      adherence to clinical practice guidelines are potential areas for further
      discussion and research.

PMID- 18631390
TI  - Genome-wide identification of microsatellites in white clover (Trifolium repens
      L.) using FIASCO and phpSSRMiner.
AB  - BACKGROUND: Allotetraploid white clover (Trifolium repens L.) is an important
      forage legume widely cultivated in most temperate regions. Only a small number of
      microsatellite markers are publicly available and can be utilized in white clover
      breeding programs. The objectives of this study were to develop an integrated
      approach for microsatellite development and to evaluate the approach for the
      development of new SSR markers for white clover. RESULTS: Genomic libraries
      containing simple sequence repeat (SSR) sequences were constructed using a
      modified Fast Isolation by AFLP of Sequences COntaining repeats (FIASCO)
      procedure and phpSSRMiner was used to develop the microsatellite markers. SSR
      motifs were isolated using two biotin-labeled probes, (CA)17 and (ATG)12. The
      sequences of 6,816 clones were assembled into 1,698 contigs, 32% of which
      represented novel sequences based on BLASTN searches. Approximately 32%, 28%, and
      16% of these SSRs contained hexa-, tri-, and di-nucleotide repeats, respectively.
      The most frequent motifs were the CA and ATG complementary repeats and the
      associated compound sequences. Primer pairs were designed for 859 SSR loci based
      on sequences from these genomic libraries and from GenBank white clover
      nucleotide sequences. A total of 191 SSR primers developed from the two libraries
      were tested for polymorphism in individual clones from the parental genotypes
      GA43 ('Durana'), 'SRVR' and six F1 progeny from a mapping population. Ninety two
      percent produced amplicons and 66% of these were polymorphic. CONCLUSION: The
      combined approach of identifying SSR-enriched fragments by FIASCO coupled with
      the primer design and in silico amplification using phpSSRMiner represents an
      efficient and low cost pipeline for the large-scale development of microsatellite
      markers in plants.The approach described here could be readily adapted and
      utilized in other non-related species with none or limited genomic resources.

PMID- 18631391
TI  - Cell autonomous expression of inflammatory genes in biologically aged fibroblasts
      associated with elevated NF-kappaB activity.
AB  - BACKGROUND: Chronic inflammation is a well-known corollary of the aging process
      and is believed to significantly contribute to morbidity and mortality of many
      age-associated chronic diseases. However, the mechanisms that cause age
      associated inflammatory changes are not well understood. Particularly, the
      contribution of cell stress responses to age-associated inflammation in 'non
      inflammatory' cells remains poorly defined. The present cross-sectional study
      focused on differences in molecular signatures indicative of inflammatory states
      associated with biological aging of human fibroblasts from donors aged 22 to 92
      years. RESULTS: Gene expression profiling revealed elevated steady-state
      transcript levels consistent with a chronic inflammatory state in fibroblast cell
      strains obtained from older donors. We also observed enhanced NF-kappaB DNA
      binding activity in a subset of strains, and the NF-kappaB profile correlated
      with mRNA expression levels characteristic of inflammatory processes, which
      include transcripts coding for cytokines, chemokines, components of the
      complement cascade and MHC molecules. This intrinsic low-grade inflammatory
      state, as it relates to aging, occurs in cultured cells irrespective of the
      presence of other cell types or the in vivo context. CONCLUSION: Our results are
      consistent with the view that constitutive activation of inflammatory pathways is
      a phenomenon prevalent in aged fibroblasts. It is possibly part of a cellular
      survival process in response to compromised mitochondrial function. Importantly,
      the inflammatory gene expression signature described here is cell autonomous,
      i.e. occurs in the absence of prototypical immune or pro-inflammatory cells,
      growth factors, or other inflammatory mediators.

PMID- 18631393
TI  - Thread embedded into penile tissue over time as an unusual hair thread tourniquet
      injury to the penis: a case report.
AB  - INTRODUCTION: Hair thread tourniquet syndrome has been recognized since the
      1960s. Since then, sporadic reports have appeared in the literature describing
      different degrees of strangulation and/or amputation of the penis caused by a
      hair thread being inadvertently tied around the penis. CASE PRESENTATION: A 9
      year-old boy presented with a 3-year history of hair thread tourniquet injury to
      his penis. Instead of the usual strangulation or amputation, the tourniquet had
      become embedded into the penile tissue, manifesting with exuberant granulation
      tissue and a tight urethral stricture. At surgery, the intact tourniquet was
      still in place, embedded in dense fibrous tissue and associated with a dense
      urethral fibrosis which measured about 2 cm long. The tourniquet was divided and
      removed, the fibrotic urethra excised and a distal penile pedicled skin flap used
      to perform a single-stage substitution urethroplasty. The patient has been
      voiding well for 28 months. CONCLUSION: This case is unusual and is the first
      report of its kind. It is also the first report of a hair thread tourniquet as
      the cause of pediatric penile injury in Nigeria.

PMID- 18631392
TI  - Evolutionary conservation of zinc finger transcription factor binding sites in
      promoters of genes co-expressed with WT1 in prostate cancer.
AB  - BACKGROUND: Gene expression analyses have led to a better understanding of growth
      control of prostate cancer cells. We and others have identified the presence of
      several zinc finger transcription factors in the neoplastic prostate, suggesting
      a potential role for these genes in the regulation of the prostate cancer
      transcriptome. One of the transcription factors (TFs) identified in the prostate
      cancer epithelial cells was the Wilms tumor gene (WT1). To rapidly identify
      coordinately expressed prostate cancer growth control genes that may be regulated
      by WT1, we used an in silico approach. RESULTS: Evolutionary conserved
      transcription factor binding sites (TFBS) recognized by WT1, EGR1, SP1, SP2, AP2
      and GATA1 were identified in the promoters of 24 differentially expressed
      prostate cancer genes from eight mammalian species. To test the relationship
      between sequence conservation and function, chromatin of LNCaP prostate cancer
      and kidney 293 cells were tested for TF binding using chromatin
      immunoprecipitation (ChIP). Multiple putative TFBS in gene promoters of placental
      mammals were found to be shared with those in human gene promoters and some were
      conserved between genomes that diverged about 170 million years ago (i.e.,
      primates and marsupials), therefore implicating these sites as candidate binding
      sites. Among those genes coordinately expressed with WT1 was the kallikrein
      related peptidase 3 (KLK3) gene commonly known as the prostate specific antigen
      (PSA) gene. This analysis located several potential WT1 TFBS in the PSA gene
      promoter and led to the rapid identification of a novel putative binding site
      confirmed in vivo by ChIP. Conversely for two prostate growth control genes,
      androgen receptor (AR) and vascular endothelial growth factor (VEGF), known to be
      transcriptionally regulated by WT1, regulatory sequence conservation was observed
      and TF binding in vivo was confirmed by ChIP. CONCLUSION: Overall, this targeted
      approach rapidly identified important candidate WT1-binding elements in genes
      coordinately expressed with WT1 in prostate cancer cells, thus enabling a more
      focused functional analysis of the most likely target genes in prostate cancer
      progression. Identifying these genes will help to better understand how gene
      regulation is altered in these tumor cells.

PMID- 18631394
TI  - Continuing trastuzumab beyond disease progression: outcomes analysis in patients
      with metastatic breast cancer.
AB  - INTRODUCTION: We performed a retrospective analysis of HER2-overexpressing
      metastatic breast cancer patients to describe clinical outcomes of those who,
      despite progression of the disease (PD), maintained trastuzumab for multiple
      chemotherapy lines. We also compared survival of these patients with that of
      those who halted trastuzumab at first PD. METHODS: We identified 101 patients
      treated between July 2000 and January 2007. Nineteen were still receiving the
      first-line trastuzumab-based treatment without evidence of PD and were not
      included in this analysis. Of the remaining 82 patients, 59 retained trastuzumab
      for one or more additional lines of chemotherapy after PD, according to our
      institution policy. Twenty-three patients who changed treating institution and
      stopped trastuzumab at first progression were used as a control group. RESULTS:
      For patients retaining trastuzumab, the median follow-up was 39.6 months.
      Clinical outcomes showed the typical degradation between first and second lines
      of therapy which we would expect by halting trastuzumab at first progression.
      Response rates were 35% and 16% and median times to progression were 7.25 and
      5.25 months for the first and second lines of trastuzumab therapy, respectively.
      The median overall survival (OS) rates were 70 months for patients who retained
      trastuzumab and 56 months for patients who halted the drug (hazard ratio [HR]
      0.87, 95% confidence interval [CI] 0.51 to 1.18; P = 0.52). If we consider OS
      from the start of trastuzumab therapy, the figures are 53.9 and 34.8 months,
      respectively (HR 0.78, 95% CI 0.58 to 1.32; P = 0.2). CONCLUSION: A
      nonstatistically significant trend of improved survival for patients retaining
      trastuzumab is observed. This is in line with most retrospective analyses and
      recent randomized data. Retaining trastuzumab after progression is a reasonable
      option, but further randomized data are warranted to better define its role in
      comparison with other available options.

PMID- 18631395
TI  - The TEAM trial: safety and efficacy of endovascular treatment of unruptured
      intracranial aneurysms in the prevention of aneurysmal hemorrhages: a randomized
      comparison with indefinite deferral of treatment in 2002 patients followed for 10
      years.
AB  - The management of patients with unruptured aneurysms remains controversial.
      Patients with unruptured aneurysms may suffer intracranial haemorrhage, but the
      incidence of this event is still debated; endovascular treatment may prevent
      rupture, but involves immediate risks. Hence, the balance of risks and benefits
      of endovascular treatment is uncertain. Here, we report the design of the TEAM
      trial, the first international, randomized, controlled trial comparing
      conservative management with endovascular treatment. Primary endpoint is
      mortality and morbidity (modified Rankin Score >/= 3) from intracranial
      haemorrhage or treatment. Secondary endpoints include incidence of hemorrhagic
      events, morbidity related to endovascular coiling, morphological results, overall
      clinical outcome and quality of life. Statistical tests compare between
      probabilities at 5- and 10-years of 1) mortality from haemorrhage related to the
      lesion, excluding per-operative complications; 2) mortality from haemorrhage or
      from complications of treatment; 3) combined disease or treatment related
      mortality and morbidity in the absence of other causes of death or disability.
      The study will be conducted in 60 international centres and will enroll 2,002
      patients equally divided between the two groups, a size sufficient to achieve 80%
      power at a 0.0167 significance to detect differences in 1) disease or treatment
      related poor outcomes from 7-9% to 3-5%; 2) overall mortality from 16 to 11%.
      Duration of the study is 14 years, the first three years being for patient
      recruitment plus a minimum of 10 years of follow-up. The TEAM trial thus offers a
      means to reconcile the introduction of a new approach with the necessity to
      acknowledge uncertainties. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN62758344 http://www.controlled-trials.com.

PMID- 18631396
TI  - Selecting short-statured children needing growth hormone testing: derivation and
      validation of a clinical decision rule.
AB  - BACKGROUND: Numerous short-statured children are evaluated for growth hormone
      (GH) deficiency (GHD). In most patients, GH provocative tests are normal and are
      thus in retrospect unnecessary. METHODS: A retrospective cohort study was
      conducted to identify predictors of growth hormone (GH) deficiency (GHD) in
      children seen for short stature, and to construct a very sensitive and fairly
      specific predictive tool to avoid unnecessary GH provocative tests. GHD was
      defined by the presence of 2 GH concentration peaks < 10 ng/ml. Certain GHD was
      defined as GHD and viewing pituitary stalk interruption syndrome on magnetic
      resonance imaging. Independent predictors were identified with uni- and multi
      variate analyses and then combined in a decision rule that was validated in
      another population. RESULTS: The initial study included 167 patients, 36 (22%) of
      whom had GHD, including 5 (3%) with certain GHD. Independent predictors of GHD
      were: growth rate < -1 DS (adjusted odds ratio: 3.2; 95% confidence interval [1.3
      7.9]), IGF-I concentration < -2 DS (2.8 [1.1-7.3]) and BMI z-score > or = 0 (2.8
      [1.2-6.5]). A clinical decision rule suggesting that patients be tested only if
      they had a growth rate < -1 DS and a IGF-I concentration < -2 DS achieved 100%
      sensitivity [48-100] for certain GHD and 63% [47-79] for GHD, and a specificity
      of 68% [60-76]. Applying this rule to the validation population (n = 40,
      including 13 patients with certain GHD), the sensitivity for certain GHD was 92%
      [76-100] and the specificity 70% [53-88]. CONCLUSION: We have derived and
      performed an internal validation of a highly sensitive decision rule that could
      safely help to avoid more than 2/3 of the unnecessary GH tests. External
      validation of this rule is needed before any application.

PMID- 18631398
TI  - Standards of English in a democratic, mass publication journal.

PMID- 18631397
TI  - Risk factors for poor virological outcome at 12 months in a workplace-based
      antiretroviral therapy programme in South Africa: a cohort study.
AB  - BACKGROUND: Reasons for the variation in reported treatment outcomes from
      antiretroviral therapy (ART) programmes in developing countries are not clearly
      defined. METHODS: Among ART-naive individuals in a workplace ART programme in
      South Africa we determined virological outcomes at 12 months, and risk factors
      for suboptimal virological outcome, defined as plasma HIV-1 viral load > or = 400
      copies/ml. RESULTS: Among 1760 individuals starting ART before July 2004, 1172
      were in follow-up at 12 months of whom 953 (81%) had a viral load measurement
      (median age 41 yrs, 96% male, median baseline CD4 count 156 x 10(6)/l). 71%
      (681/953) had viral load < 400 copies/ml at 12 months. In a multivariable
      analysis, independent predictors of suboptimal virological outcome at 12 months
      were <1 log decrease in viral load at six weeks (odds ratio [OR] 4.71, 95%
      confidence interval [CI] 2.56-8.68), viral load at baseline (OR 3.63 [95% CI 1.88
      7.00] and OR 3.54 [95% CI 1.79-7.00] for 10,001-100,000 and >100,000 compared to
      < or = 10,000 copies/ml, respectively), adherence at six weeks (OR 3.50 [95% CI
      1.92-6.35]), WHO stage (OR 2.08 [95% CI 1.28-3.34] and OR 2.03 [95% CI 1.14-3.62]
      for stage 3 and 4 compared to stage 1-2, respectively) and site of ART delivery.
      Site of delivery remained an independent risk factor even after adjustment for
      individual level factors. At 6 weeks, of 719 patients with self-reported
      adherence and viral load, 72 (10%) reported 100% adherence but had <1 log
      decrease in viral load; conversely, 60 (8%) reported <100% adherence but had > or
      = 1 log decrease in viral load. CONCLUSION: Virological response at six weeks
      after ART start was the strongest predictor of suboptimal virological outcome at
      12 months, and may identify individuals who need interventions such as additional
      adherence support. Self reported adherence was less strongly associated but
      identified different patients compared with viral load at 6 weeks. Site of
      delivery had an important influence on virological outcomes; factors at the
      health system level which influence outcome need further investigation to guide
      development of effective ART programmes.

PMID- 18631399
TI  - Successful transureteropyelostomy after heminephrectomy of a bilateral
      hydronephrotic horseshoe kidney: a case report.
AB  - INTRODUCTION: Horseshoe kidney is a rare congenital malformation that is found in
      approximately 0.25% of the general population and usually remains asymptomatic.
      CASE PRESENTATION: We report a successful transureteropyelostomy after
      heminephrectomy of the non-functional right moiety in a 25-year-old man with
      horseshoe kidney who had a combined 50% functional loss and hydronephrosis due to
      multiple distal ureteral strictures on the functionally remaining left side.
      Continuous ureteral stenting of the remaining part of the former horseshoe kidney
      was avoided during a follow-up of 2 years. CONCLUSION: Urologists are often faced
      with technically difficult cases that are not responsive to standard operative
      procedures, and this case illustrates an individual surgical approach in a
      clinical situation.

PMID- 18631400
TI  - CD45 immunoaffinity depletion of vesicles from Jurkat T cells demonstrates that
      exosomes contain CD45: no evidence for a distinct exosome/HIV-1 budding pathway.
AB  - The presence of relatively high levels of cellular protein contamination in
      density-purified virion preparations is a confounding factor in biochemical
      analyses of HIV and SIV produced from hematopoietic cells. A major source of this
      contamination is from vesicles, either microvesicles or exosomes, that have
      similar physical properties as virions. Thus, these particles can not be removed
      by size or density fractionation. Although virions and vesicles have similar
      cellular protein compositions, CD45 is excluded from HIV-1 yet is present in
      vesicles produced from hematopoietic cells. By exploiting this finding, we have
      developed a CD45 immunoaffinity depletion procedure that removes vesicles from
      HIV-1 preparations. While this approach has been successfully applied to virion
      preparations from several different cell types, some groups have concluded that
      "exosomes" from certain T cell lines, specifically Jurkat, do not contain CD45.
      If this interpretation is correct, then these vesicles could not be removed by
      CD45 immunoaffinity depletion. Here we show that dense vesicles produced by
      Jurkat and SupT1/CCR5 cells contain CD45 and are efficiently removed from
      preparations by CD45-immunoaffinity depletion. Also, contaminating cellular
      proteins were removed from virion preparations produced by these lines.
      Previously, the absence of CD45 from both "exosomes" and virions has been used to
      support the so called Trojan exosome hypothesis, namely that HIV-1 is simply an
      exosome containing viral material. The presence of CD45 on vesicles, including
      exosomes, and its absence on virions argues against a specialized budding pathway
      that is shared by both exosomes and HIV-1.

PMID- 18631401
TI  - Genes responsive to both oxidant stress and loss of estrogen receptor function
      identify a poor prognosis group of estrogen receptor positive primary breast
      cancers.
AB  - INTRODUCTION: Oxidative stress can modify estrogen receptor (ER) structure and
      function, including induction of progesterone receptor (PR), altering the biology
      and clinical behavior of endocrine responsive (ER-positive) breast cancer.
      METHODS: To investigate the impact of oxidative stress on estrogen/ER-regulated
      gene expression, RNA was extracted from ER-positive/PR-positive MCF7 breast
      cancer cells after 72 hours of estrogen deprivation, small-interfering RNA
      knockdown of ER-alpha, short-term (8 hours) exposure to various oxidant stresses
      (diamide, hydrogen peroxide, and menadione), or simultaneous ER-alpha knockdown
      and oxidant stress. RNA samples were analyzed by high-throughput expression
      microarray (Affymetrix), and significance analysis of microarrays was used to
      define gene signatures responsive to estrogen/ER regulation and oxidative stress.
      To explore the association of these signatures with breast cancer biology,
      microarray data were analyzed from 394 ER-positive primary human breast cancers
      pooled from three independent studies. In particular, an oxidant-sensitive
      estrogen/ER-responsive gene signature (Ox-E/ER) was correlated with breast cancer
      clinical parameters and disease-specific patient survival (DSS). RESULTS: From
      891 estrogen/ER-regulated probes, a core set of 75 probes (62 unique genes)
      responsive to all three oxidants were selected (Ox-E/ER signature). Ingenuity
      pathway analysis of this signature highlighted networks involved in development,
      cancer, and cell motility, with intersecting nodes at growth factors (platelet
      derived growth factor-BB, transforming growth factor-beta), a proinflammatory
      cytokine (tumor necrosis factor), and matrix metalloproteinase-2. Evaluation of
      the 394 ER-positive primary breast cancers demonstrated that Ox-E/ER index values
      correlated negatively with PR mRNA levels (rp = -0.2; P = 0.00011) and positively
      with tumor grade (rp = 0.2; P = 9.741 x e-5), and were significantly higher in ER
      positive/PR-negative versus ER-positive/PR-positive breast cancers (t-test, P =
      0.0008). Regardless of PR status, the Ox-E/ER index associated with reduced DSS
      (n = 201; univariate Cox, P = 0.078) and, using the optimized cut-point,
      separated ER-positive cases into two significantly different DSS groups (log
      rank, P = 0.0009). CONCLUSION: An oxidant-sensitive subset of estrogen/ER
      responsive breast cancer genes linked to cell growth and invasion pathways was
      identified and associated with loss of PR and earlier disease-specific mortality,
      suggesting that oxidative stress contributes to the development of an aggressive
      subset of primary ER-positive breast cancers.

PMID- 18631402
TI  - Systematic analysis of the effect of multiple templates on the accuracy of
      comparative models of protein structure.
AB  - BACKGROUND: Although multiple templates are frequently used in comparative
      modeling, the effect of inclusion of additional template(s) on model accuracy
      (when compared to that of corresponding single-template based models) is not
      clear. To address this, we systematically analyze two-template models, the
      simplest case of multiple-template modeling. For an existing target-template pair
      (single-template modeling), a two-template based model of the target sequence is
      constructed by including an additional template without changing the original
      alignment to measure the effect of the second template on model accuracy.
      RESULTS: Even though in a large number of cases a two-template model showed
      higher accuracy than the corresponding one-template model, over the entire
      dataset only a marginal improvement was observed on average, as there were many
      cases where no change or the reverse change was observed. The increase in
      accuracy due to the structural complementarity of the templates increases at
      higher alignment accuracies. The combination of templates showing the highest
      potential for improvement is that where both templates share similar and low
      (less than 30%) sequence identity with the target, as well as low sequence
      identity with each other. The structural similarity between the templates also
      helps in identifying template combinations having a higher chance of resulting in
      an improved model. CONCLUSION: Inclusion of additional template(s) does not
      necessarily improve model quality, but there are distinct combinations of the two
      templates, which can be selected a priori, that tend to show improvement in model
      quality over the single template model. The benefit derived from the structural
      complementarity is dependent on the accuracy of the modeling alignment. The study
      helps to explain the observation that a careful selection of templates together
      with an accurate target:template alignment are necessary to the benefit from
      using multiple templates in comparative modeling and provides guidelines to
      maximize the benefit from using multiple templates. This enables formulation of
      simple template selection rules to rank targets of a protein family in the
      context of structural genomics.

PMID- 18631403
TI  - Function2Gene: a gene selection tool to increase the power of genetic association
      studies by utilizing public databases and expert knowledge.
AB  - BACKGROUND: Many common disorders have multiple genetic components which convey
      increased susceptibility. SNPs have been used to identify genetic components
      which are associated with a disease. Unfortunately, many studies using these
      methods suffer from low reproducibility due to lack of power. RESULTS: We present
      a set of programs which implement a novel method for searching for disease
      associated genes using prior information to select and order genes from publicly
      available databases by their prior likelihood of association with the disease.
      These programs were used in a published study of childhood-onset SLE which
      yielded novel associations with modest sample size. CONCLUSION: Using prior
      information to decrease the size of the problem space to an amount commensurate
      with available samples and resources while maintaining appropriate power enables
      researchers to increase their likelihood of discovering reproducible
      associations.

PMID- 18631404
TI  - Linkage of health and aged care service events: comparing linkage and event
      selection methods.
AB  - BACKGROUND: Data linkage is a technique that has long been used to connect
      information across several disparate data sources--most commonly for medical and
      population health research. Often the purpose is to connect data for individuals
      over extended time periods or across different service settings, and so person
      based linkage using detailed personal information is preferred. Linkage which
      aims to link connected events, on the other hand, requires information about the
      time and place of the event as well as the person or persons involved in that
      event in order to make high quality linkages. This paper describes the detailed
      process of event linkage and compares directly an event-based linkage method for
      identifying transition events between two care sectors in Australia with a well
      established high quality longitudinal person-based linkage which facilitates
      identification of event data for individuals. METHODS: Direct comparisons are
      made between transition events identified using an event-based linkage and an
      existing person-based linkage for people moving from hospital into aged care in
      Western Australia. Several aspects of event-based linkage are examined:
      refinement of the strategy to reduce false positives, causes of false positives
      and false negatives, quality of the linked event dataset, and utility of the
      linked event dataset for transition analysis. RESULTS: Over 97% of the event
      based links were among those selected using the person-based linkage and over 90%
      of the latter were identified by the event-based method, with the remainder
      missed mostly due to differences in reported event date or residential region.
      Consequently the two linked datasets were sufficiently similar to give very
      similar results for analyses, but the actual volume of movement from hospital to
      RAC was underestimated by about 10% by the event-based method. CONCLUSION: This
      project has allowed a 'preferred event' event-based linkage strategy to be
      selected and deployed across Australia to study movements from hospital to
      residential aged care facilities using databases in which only limited personal
      information is available, but event dates and details can be readily accessed.
      The utility of this approach in other transition situations depends on the volume
      of movement and the accuracy of recording information in each setting.

PMID- 18631405
TI  - Dinucleotide repeat polymorphism in Fms-like tyrosine kinase-1 (Flt-1) gene is
      not associated with preeclampsia.
AB  - BACKGROUND: Preeclampsia is a major cause of maternal and perinatal mortality and
      morbidity. The etiology of preeclampsia remains unclear. Recently, it was shown
      that misregulation of fms-like tyrosine kinase-1 (Flt-1) in the peripheral blood
      mononuclear cells of pregnant women results in over-expression of the soluble
      splice variant of Flt-1, sFlt-1, producing an additional (extra-placental) source
      of sFlt-1 that can contribute to the etiology of preeclampsia. The aim of this
      study was to investigate the relationship between preeclampsia and a dinucleotide
      (threonine-glycine; TG)n repeat polymorphism in the 3' non-coding region of the
      Flt-1 gene. METHODS: The number of the d(TG)n repeats was analyzed in 170
      patients with preeclampsia and in 202 normotensive pregnancies. The region
      containing the dinucleotide repeat polymorphism of the Flt-1 gene was amplified
      by polymerase chain reaction (PCR) from the DNA samples and was analyzed by
      direct PCR sequencing. RESULTS: We found 10 alleles of the dinucleotide repeat
      polymorphism and designated these as allele*12 (A1) through allele*23 (A12)
      according to the number of the TG repeats, from 12 to 23. The frequency of the 14
      repeat allele (A3) was most abundant (63.82% in preeclampsia and 69.06% in
      controls), followed by the 21-repeat allele (A10; 28.53% in preeclampsia and
      23.76% in controls). There was no significant difference in the allele frequency
      between patients with preeclampsia and normal controls. The most common genotype
      in preeclamptic and normotensive pregnancies was heterozygous (TG)14/(TG)21
      (41.76%) and homozygous (TG)14/(TG)14 (45.05%), respectively. However, the
      genotype frequencies were not significantly different between preeclamptic
      patients and controls. CONCLUSION: This is the first study to characterize the
      dinucleotide repeat polymorphism of the Flt-1 gene in patients with preeclampsia.
      We found no differences in the allele or genotype frequencies between patients
      with preeclampsia and normal pregnancies. Although limited by a relatively small
      sample size, our study suggests that the d(TG)n repeat polymorphism of the Flt-1
      gene is not associated with the development of preeclampsia in Korean pregnant
      women.

PMID- 18631406
TI  - Laypersons' understanding of relative risk reductions: randomised cross-sectional
      study.
AB  - BACKGROUND: Despite increasing recognition of the importance of involving
      patients in decisions on preventive healthcare interventions, little is known
      about how well patients understand and utilise information provided on the
      relative benefits from these interventions. The aim of this study was to explore
      whether lay people can discriminate between preventive interventions when
      effectiveness is presented in terms of relative risk reduction (RRR), and whether
      such discrimination is influenced by presentation of baseline risk. METHODS: The
      study was a randomised cross-sectional interview survey of a representative
      sample (n = 1,519) of lay people with mean age 59 (range 40-98) years in Denmark.
      In addition to demographic information, respondents were asked to consider a
      hypothetical drug treatment to prevent heart attack. Its effectiveness was
      randomly presented as RRR of 10, 20, 30, 40, 50 or 60 percent, and half of the
      respondents were presented with quantitative information on the baseline risk of
      heart attack. The respondents had also been asked whether they were diagnosed
      with hypercholesterolemia or had experienced a heart attack. RESULTS: In total,
      873 (58%) of the respondents consented to the hypothetical treatment. While 49%
      accepted the treatment when RRR = 10%, the acceptance rate was 58-60% for RRR>10.
      There was no significant difference in acceptance rates across respondents
      irrespective of whether they had been presented with quantitative information on
      baseline risk or not. CONCLUSION: In this study, lay people's decisions about
      therapy were only slightly influenced by the magnitude of the effect when it was
      presented in terms of RRR. The results may indicate that lay people have
      difficulties in discriminating between levels of effectiveness when they are
      presented in terms of RRR.

PMID- 18631407
TI  - Quantification of mRNA in single cells and modelling of RT-qPCR induced noise.
AB  - BACKGROUND: Gene expression has a strong stochastic element resulting in highly
      variable mRNA levels between individual cells, even in a seemingly homogeneous
      cell population. Access to fundamental information about cellular mechanisms,
      such as correlated gene expression, motivates measurements of multiple genes in
      individual cells. Quantitative reverse transcription PCR (RT-qPCR) is the most
      accessible method which provides sufficiently accurate measurements of mRNA in
      single cells. RESULTS: Low concentration of guanidine thiocyanate was used to
      fully lyse single pancreatic beta-cells followed by RT-qPCR without the need for
      purification. The accuracy of the measurements was determined by a quantitative
      noise-model of the reverse transcription and PCR. The noise is insignificant for
      initial copy numbers >100 while at lower copy numbers the noise intrinsic of the
      PCR increases sharply, eventually obscuring quantitative measurements.
      Importantly, the model allows us to determine the RT efficiency without using
      artificial RNA as a standard. The experimental setup was applied on single
      endocrine cells, where the technical and biological noise levels were determined.
      CONCLUSION: Noise in single-cell RT-qPCR is insignificant compared to biological
      cell-to-cell variation in mRNA levels for medium and high abundance transcripts.
      To minimize the technical noise in single-cell RT-qPCR, the mRNA should be
      analyzed with a single RT reaction, and a single qPCR reaction per gene.

PMID- 18631408
TI  - Female voiding dysfunction.
AB  - Female voiding dysfunction unrelated to childbirth is common but poorly
      understood, and most often occurs as a result of detrusor hypotonia and less
      frequently in association with bladder outlet obstruction. Specific causes
      include anti-incontinence surgery, bladder over-distension, painful infective,
      allergic or chemical reactions of the urogenital tissues, bladder outlet
      obstruction, dyssynergia of the bladder-urethral sphincter mechanism, neurogenic,
      pharmacological, and psychogenic causes. A thorough history and examination is
      essential in the clinical assessment. It should be followed by investigations
      including urine microbiology, frequency volume diaries, ultrasound scan,
      uroflowmetry, and, when indicated, subtracted voiding cystometry,
      electromyography, and cystourethroscopy. The main treatment modalities are
      catheterization (self-intermittent, suprapubic, urethral, in order of
      preference), bladder retraining, biofeedback, and, rarely, surgery or sacral
      neuromodulation.

PMID- 18631409
TI  - Female sexual dysfunction in obstetrics and gynecology.
AB  - Sexual dysfunction in women is common, with a community prevalence of 30% to 50%.
      The sexual response cycle in women is complex, with multiple overlapping
      dimensions, which necessitates a biopsychosocial approach for understanding the
      basis of dysfunction. Physiological events such as pregnancy, childbirth,
      menopause, aging as well as gynecological conditions like infertility, prolapse,
      urinary incontinence, and gynecological cancers, have an impact on sexual well
      being. The interaction of these conditions with sexual health needs to be better
      understood to deal effectively with the problems as a whole. However, the woman
      concerned should be sufficiently distressed by her problem for the diagnosis of
      female sexual dysfunction to be made. Overall, gynecological surgery performed to
      alleviate symptoms which have an organic basis have the potential to improve
      sexual function, and this does not necessarily correlate with the anatomical
      outcome of the surgery. Hysterectomy done by any approach does not compromise
      sexual function. Sexual health enquiry and evaluation in clinical practice can be
      done with the help of simple screening questions, a comprehensive history
      followed by an adequate examination. As no single laboratory test is recommended
      as a marker of sexual dysfunction, investigations are best dictated by clinical
      judgment. Detailed assessment tools in the form of self-report questionnaires and
      diagnostic tests for objective measures of sexual dysfunction could be used in
      special circumstances. Therapy entails understanding the point of break in the
      sexual response cycle and the underlying pathophysiology. While there are
      multiple treatment options available, integrated therapy which deals with both
      the psyche and the soma yield best results. Sexual counseling plays a vital role
      when therapy becomes necessary.

PMID- 18631410
TI  - Predicting success and reducing the risks when attempting vaginal birth after
      cesarean.
AB  - The goal of this manuscript is to review the contemporary evidence on issues
      pertinent to improving the safety profile of vaginal birth after cesarean (VBAC)
      attempts. Patients attempting VBAC have success rates of 60%-80%, and no reliable
      method of predicting VBAC failure for individual patients exists. The rate of
      uterine rupture in all patients ranges from 0.7% to 0.98%, but the rate of
      uterine rupture decreases in patients with a prior vaginal delivery. In fact, in
      patients with a prior vaginal delivery, VBAC appears to be safer from the
      maternal standpoint than repeat cesarean. Inevitably, the obstetrician today will
      encounter the situation of deciding whether or not to induce a patient with a
      uterine scar, and particular attention is paid to the success and risks of
      inducing labor in this patient population. Induction of labor is associated with
      a slightly lower successful vaginal delivery rate, although the rate remains
      above 50% in virtually all patient populations. The rate of uterine rupture
      increases slightly, but still remains around 2%-3%. Although misoprostol use is
      discouraged due to its association with increased risks of uterine rupture,
      transcervical catheters, oxytocin, and amniotomy may be used to induce labor in
      women attempting VBAC.

PMID- 18631411
TI  - Recognition of facial emotion in low vision: a flexible usage of facial features.
AB  - Age-related macular degeneration (AMD) is a major cause of visual impairment in
      people older than 50 years in Western countries, affecting essential tasks such
      as reading and face recognition. Here we investigated the mechanisms underlying
      the deficit in recognition of facial expressions in an AMD population with low
      vision. Pictures of faces displaying different emotions with the mouth open or
      closed were centrally displayed for 300 ms. Participants with AMD with low acuity
      (mean 20/200) and normally sighted age-matched controls performed one of two
      emotion tasks: detecting whether a face had an expression or not (expressive/non
      expressive (EXNEX) task) or categorizing the facial emotion as happy, angry, or
      neutral (categorization of expression (CATEX) task). Previous research has shown
      that healthy observers are mainly using high spatial frequencies in an EXNEX task
      while performance at a CATEX task was preferentially based on low spatial
      frequencies. Due to impaired processing of high spatial frequencies in central
      vision, we expected and observed that AMD participants failed at deciding whether
      a face was expressive or not but categorized normally the emotion of the face
      (e.g., happy, angry, neutral). Moreover, we observed that AMD participants mostly
      identified emotions using the lower part of the face (mouth). Accuracy did not
      differ between the two tasks for normally sighted observers. The results indicate
      that AMD participants are able to identify facial emotion but must base their
      decision mainly on the low spatial frequencies, as they lack the perception of
      finer details.

PMID- 18631412
TI  - The effect of exogenous cholesterol and lipid-modulating agents on enterocytic
      amyloid-beta abundance.
AB  - Dietary cholesterol may influence Alzheimer's disease risk, because it regulates
      the synthesis of amyloid-beta. It was recently demonstrated in enterocytes of
      wild-type mice that intracellular amyloid-beta expression is enhanced in response
      to a high-fat diet made up of SFA and cholesterol. Intestinally derived amyloid
      beta may be associated with postprandial lipoproteins in response to dietary fats
      and could be a key regulator in chylomicron metabolism. The present study was
      designed to investigate the role of cholesterol in modulating amyloid-beta
      abundance in enterocytes. Wild-type mice were fed a low-fat diet supplemented
      with 2 % (w/w) cholesterol. The effects of cholesterol absorption inhibition and
      cholesterol biosynthesis inhibition utilising ezetimibe and atorvastatin,
      respectively, were also studied. Quantitative immunohistochemistry was utilised
      to determine enterocytic amyloid-beta homeostasis. We found that enterocytic
      amyloid-beta concentration was significantly attenuated in mice fed the 2 % (w/w)
      cholesterol diet. However, blocking cholesterol absorption reversed the
      cholesterol-feeding effect. Consistent with a suppressive effect of cholesterol
      on enterocytic amyloid-beta abundance, atorvastatin, an inhibitor of cholesterol
      biosynthesis, enhanced amyloid-beta. However, providing exogenous cholesterol
      abolished the atorvastatin-induced effect. In contrast to the suppression of
      enterocytic amyloid-beta by dietary cholesterol, mice fed a diet enriched in SFA
      had markedly greater abundance. Collectively, the findings suggest that exogenous
      and endogenous cholesterol reduce amyloid-beta concentration in enterocytes by
      suppressing production, or enhancing secretion associated with postprandial
      lipoproteins. Intestinally derived amyloid-beta will contribute to the pool of
      plasma protein and may influence cerebral amyloid homeostasis by altering the bi
      directional transfer across the blood-brain barrier.

PMID- 18631413
TI  - Analysis of the impact of fortified food consumption on overall dietary quality
      in Irish adults.
AB  - The aim of the present study was to assess the impact of fortified food (FF)
      consumption on overall dietary quality in Irish adults. Data for this analysis
      was based on the North/South Ireland Food Consumption Survey w7/15/2008hich used
      a 7 d food diary to collect food and beverage intake data in a representative
      sample of 1379 Irish adults (662 men and 717 women) aged 18-64 years. Foods
      contained in the database that are fortified were identified from the presence of
      vitamins and/or minerals in the ingredient list on the label. The results showed
      that an increased level of FF consumption was associated with lower intakes
      (percentage food energy) of total fat and saturated fat (women only) and higher
      intakes of total carbohydrate, total sugars (but not added sugars) and starch.
      Increased consumption was associated with a more micronutrient-dense diet and a
      reduced prevalence of dietary inadequacies of Ca, Fe, riboflavin and folate,
      particularly in women. Higher FF consumption was associated with higher intakes
      of fruit, lower intakes of alcohol and a lower likelihood of smoking in men and
      women. Thus it appears that FF consumption is a marker of both better dietary
      quality and healthy lifestyle behaviours.

PMID- 18631414
TI  - Prevalence and predictors of vitamin D inadequacy amongst Lebanese osteoporotic
      women.
AB  - In Middle-Eastern countries, more particularly in Lebanon, the incidence of
      vitamin D deficiency has been found to be surprisingly high in schoolchildren and
      young individuals. However, the prevalence and risk factors for vitamin D
      inadequacy amongst Lebanese osteoporotic women seeking medical health care has
      never been studied. We analysed vitamin D-inadequacy risk factors among the 251
      Lebanese postmenopausal osteoporotic women (from both Muslim and Christian
      communities) who participated in a vitamin D international epidemiological study.
      Vitamin D inadequacy prevalence (25-hydroxyvitamin D (25(OH)D) , 30 ng/ml) was
      84.9%. 25(OH)D was negatively correlated with BMI (r 20.41; P<0.001) and
      positively correlated with educational level (r 0.37; P<0.001) and self-reported
      general health (r 0.17; P<0.01). No significant correlation was found with age
      and no seasonal variation was observed. There was no significant correlation
      between 25(OH)D and sun exposure index or vitamin D-rich food consumption.
      However, 25(OH)D strongly correlated with vitamin D supplement intake (r 0.48;
      P<0.0001). Muslim community participants had lower 25(OH)D levels compared with
      their Christian counterparts (P<0.001). They also had higher BMI, lower
      educational level and vitamin D supplement consumption and followed more
      frequently a dress code covering the arms (P<0.0001 for all variables). In a
      multivariate model, in Muslims, inadequate vitamin D supplements and a dress code
      covering the arms are the independent predictors of 25(OH)D inadequacy (P<0.001
      for both variables). However, in Christians, the predictors are inadequate
      vitamin D supplements, high BMI and low educational level (P<0.001; P=002 and
      P=0.02 respectively). There is an urgent need to increase vitamin D supplement
      use in Middle-Eastern osteoporotic women, more particularly in those from the
      Muslim community.

PMID- 18631415
TI  - Predictors of 25-hydroxyvitamin D status among adults in two British national
      surveys.
AB  - Several recent reports have found a high prevalence of vitamin D deficiency in
      the adult British population. The present paper investigates the associations of
      low income/material deprivation and other predictors of serum 25-hydroxyvitamin D
      (25(OH)D) status in two surveys: The National Diet and Nutrition Survey (NDNS) of
      the population aged 19-64 years in mainland Britain and the Low Income Diet and
      Nutrition Survey (LIDNS) of adults aged > or = 19 years in all regions of the UK
      who were screened to identify low-income/materially deprived households. A valid
      serum 25(OH)D sample was obtained in 1297 and 792 participants from the NDNS and
      LDNS respectively. The NDNS participants who were not receiving benefits (n 1054)
      had a mean 25(OH)D of 50.1 nmol/l, which was higher than among NDNS participants
      receiving benefits (n 243) with a mean 25(OH)D of 43.0 nmol/l (P < 0.001) and the
      LIDNS sample (46.5 nmol/l; P < 0.05). For all three samples, the season of
      drawing blood, skin colour, dietary intake of vitamin D, and intake of dietary
      supplements were significant predictors (P < 0.05) of serum 25(OH)D status in
      mutually adjusted regression models. National prevention and treatments
      strategies of poor vitamin D status need to be targeted to include the adult
      population, particularly deprived populations, in addition to the elderly and
      ethnic minorities.

PMID- 18631417
TI  - Anti-inflammatory effects of long-chain n-3 PUFA in rhinovirus-infected cultured
      airway epithelial cells.
AB  - Long-chain n-3 PUFA (LCn-3PUFA) including DHA and EPA, are known to decrease
      inflammation by inhibiting arachidonic acid (AA) metabolism to eicosanoids,
      decreasing the production of pro-inflammatory cytokines and reducing immune cell
      function. The aim of this study was to determine if EPA and DHA reduced the
      release of inflammatory mediators from airway epithelial cells infected with
      rhinovirus (RV). Airway epithelial cells (Calu-3) were incubated with EPA, DHA
      and AA for 24 h, followed by rhinovirus infection for 48 h. IL-6, IL-8 and
      interferon-gamma-induced protein-10 (IP-10) released by cells were measured using
      ELISA. Viral replication was measured by serial titration assays. The fatty acid
      content of cells was analysed using GC. Cellular viability was determined by
      visual inspection of cells and lactate dehydrogenase release. DHA (400 microm)
      resulted in a significant 16% reduction in IL-6 release after RV-43 infection,
      29% reduction in IL-6 release after RV-1B infection, 28% reduction in IP-10
      release after RV-43 infection and 23 % reduction in IP-10 release after RV-1B
      infection. Cellular DHA content negatively correlated with IL-6 and IP-10
      release. None of the fatty acids significantly modified rhinovirus replication.
      DHA supplementation resulted in increased cellular content of DHA at the cost of
      AA, which may explain the decreased inflammatory response of cells. EPA and AA
      did not change the release of inflammatory biomarkers significantly. It is
      concluded that DHA has a potential role in suppressing RV-induced airway
      inflammation.

PMID- 18631416
TI  - Maternal fatty acid intake and fetal growth: evidence for an association in
      overweight women. The 'EDEN mother-child' cohort (study of pre- and early
      postnatal determinants of the child's development and health).
AB  - Recent studies suggest a benefit of seafood and n-3 fatty acid intake on fetal
      growth and infant development. The objective was to study the association between
      fatty acid intake and fetal growth in pregnant French women. Pregnant women
      included in the EDEN mother-child cohort study completed FFQ on their usual diet:
      (1) in the year before pregnancy and (2) during the last 3 months of pregnancy (n
      1439). Conversion into nutrient intakes was performed using data on portion size
      and a French food composition table. Associations between maternal fatty acid
      intakes and several neonatal anthropometric measurements were studied using
      linear regressions adjusted for centre, mother's age, smoking habits, height,
      parity, gestational age and newborn's sex. Due to significant interaction,
      analyses were stratified according to maternal pre-pregnancy overweight status.
      Neither total lipid nor SFA, MUFA or PUFA intake was significantly associated
      with newborn size. In overweight women only (n 366), a high pre-pregnancy n-3
      fatty acid intake (% PUFA) was positively associated with the newborn's birth
      weight (P=0.01), head, arm and wrist circumferences and sum of skinfolds
      (P<0.04). A substitution of 1% of n-3 fatty acids per d before pregnancy by other
      PUFA was related to an average decrease in birth weight of 60 g (P=0.01).
      Relationships with n-3 fatty acid intake at the end of pregnancy were weaker and
      not significant. We concluded that a high pre-pregnancy n-3 fatty acid:PUFA ratio
      may sustain fetal growth in overweight women. Follow-up of the children may help
      determine whether this has beneficial consequences for the child's health and
      development.

PMID- 18631418
TI  - Analysis of fat and muscle mass in patients with inflammatory bowel disease
      during remission and active phase.
AB  - Inflammatory bowel disease (IBD) is often associated with malnutrition. The aim
      of this study was to compare the body composition of outpatients with IBD during
      remission and active phase. In order to evaluate disease activity we used Crohn's
      Disease Activity Index for Crohn's disease (CD) patients and Lichtiger's Index
      for ulcerative colitis (UC) patients. All patients underwent the analysis of BMI,
      arm muscle area (AMA) and triceps plus subscapula skinfold thickness (TST+SST) to
      identify total, muscle and fat mass, respectively. In total 102 patients were
      evaluated (CD, n 50; UC, n 52) and the majority was young women. Malnutrition
      according to BMI was found in 14.0 % of patients with CD and 5.7 % of UC
      patients. Muscle mass depletion was detected in more than half of the CD and UC
      patients. The BMI, TST+SST and AMA values were lower in the active phase only in
      CD patients (P < 0.05). Fat mass depletion was associated with active phase in
      both CD and UC patients. Body composition parameters obtained using BMI, TST+SST
      and AMA were not correlated with the presence of fistula in CD patients (P>0.05).
      In conclusion, patients without signs of malnutrition had fat mass depletion
      especially in the active phase and muscle mass depletion occurred both in CD and
      UC patients.

PMID- 18631419
TI  - Inheritance of Cry1F resistance in laboratory-selected European corn borer and
      its survival on transgenic corn expressing the Cry1F toxin.
AB  - A major assumption of the high-dose/refuge strategy proposed for insect
      resistance management strategies for transgenic crop plants that express toxins
      from Bacillus thuringiensis is that resistance traits that evolve in pest species
      will be recessive. The inheritance of Cry1F resistance and larval survival on
      commercially available Cry1F corn hybrids were determined in a laboratory
      selected strain of European corn borer, Ostrinia nubilalis (Hubner), displaying
      more than 3000-fold resistance to Cry1F. Concentration-response bioassays of
      reciprocal parental crosses indicated that the resistance is autosomal and
      recessive. Bioassays of the backcross of the F1 generation with the selected
      strain were consistent with the hypothesis that a single locus, or a set of
      tightly linked loci, is responsible for the resistance. Greenhouse experiments
      with Cry1F-expressing corn hybrids indicated that some resistant larvae survived
      the high dose of toxin delivered by Cry1F-expressing plants although F1 progeny
      of susceptible by resistant crosses had fitness close to zero. These results
      provide the first direct evidence that the high dose/refuge strategy currently in
      place to manage resistance in Cry1F-expressing corn is appropriate.

PMID- 18631420
TI  - Molecular markers to discriminate among four pest species of Helicoverpa
      (Lepidoptera: Noctuidae).
AB  - The four significant pest species in the Helicoverpa genus (H. armigera, H.
      assulta, H. punctigera and H. zea) are morphologically similar and can only be
      reliably distinguished through dissection of adult genitalia. Two partial regions
      of the mitochondrial DNA (mtDNA), the cytochrome oxidase subunit I (COI) and the
      cytochrome b (Cyt b) genes were amplified by PCR and digested with restriction
      endonucleases. The restriction patterns, generated by the endonucleases BstZ17I
      and HphI, demonstrated reliable differentiation of the four Helicoverpa pest
      species. This technique is fast, reliable and effective at distinguishing
      specimens irrespective of their life stages and offers support to conventional
      taxonomic differentiation based on morphological characters.

PMID- 18631422
TI  - Cost-effectiveness analysis of a hypothetical hepatitis C vaccine compared to
      antiviral therapy.
AB  - We propose a mathematical model to simulate the dynamics of hepatitis C virus
      (HCV) infection in the state of Sao Paulo, Brazil. We assumed that a hypothetical
      vaccine, which cost was taken to be the initial cost of the vaccine against
      hepatitis B exists and it is introduced in the model. We computed its cost
      effectiveness compared with the anti-HCV therapy. The calculated basic
      reproduction number was 1.20. The model predicts that without intervention a
      steady state exists with an HCV prevalence of 3%, in agreement with the current
      epidemiological data. Starting from this steady state three interventions were
      simulated: indiscriminate vaccination, selective vaccination and anti-HCV
      therapy. Selective vaccination proved to be the strategy with the best cost
      effectiveness ratio, followed by indiscriminate vaccination and anti-HCV therapy.

PMID- 18631421
TI  - Inhibition of the histamine-induced Ca2+ influx in primary human endothelial
      cells (HUVEC) by volatile anaesthetics.
AB  - BACKGROUND AND OBJECTIVE: Vasoactive substances such as histamine, acetylcholine
      or ATP increase the [Ca2+]i of endothelial cells, which leads to the activation
      of nitric oxide synthase (eNOS). The NO produced by this enzyme relaxes the
      underlying smooth muscle. Evidence suggests that eNOS activation is dependent on
      agonist-induced Ca2+ entry. Recently we have shown that in human endothelial
      cells (HUVEC), this Ca2+ entry is sensitive to isoflurane. The objective here was
      to study the mechanism by which volatile anaesthetics can depress the histamine
      induced Ca2+ entry into HUVEC cells. METHODS: HUVECs on coverslips were loaded
      with the Ca2+ indicator Fluo-3 and inserted in a gastight, temperature-controlled
      perfusion chamber. Excitation was at 488 nm and fluorescence signals were
      monitored with a confocal laser scanning microscope (MRC1024, Biorad). Direct
      measurement of the Ca2+ influx was with Mn2+ as surrogate for calcium at 360 nm
      in cells loaded with Fura-2. RESULTS: Addition of histamine induces a biphasic
      [Ca2+]i increase consisting of Ca2+ release from internal stores and a Ca2+
      influx from the external medium (plateau phase). The plateau phase was dose
      dependently inhibited by enflurane and sevoflurane (13.7 resp. 21.9% inhibition
      by 1 MAC anaesthetic). Direct measurement of the Ca2+ influx using the Mn2+
      quench of the Fura-2 fluorescence gave similar results. The inhibition of the
      anaesthetics was not reduced by inhibition of the cGMP pathway, inactivation of
      protein kinase C, depolarization of the cells or the presence of specific Ca2+
      dependent K+ channel inhibitors. Interestingly, unsaturated fatty acids inhibit
      the histamine-induced Ca2+ influx in a similar way as the volatile anaesthetics.
      CONCLUSIONS: Volatile anaesthetics dose-dependently inhibit the histamine-induced
      Ca2+ influx in HUVECs by a mechanism that may involve unspecific perturbation of
      the lipid bilayer.

PMID- 18631423
TI  - Molecular characterization and epidemiology of the highly pathogenic avian
      influenza H5N1 in Nigeria.
AB  - Avian influenza caused infection and spread throughout Nigeria in 2006. Carcass
      samples (lung, liver, spleen, heart, trachea and intestine) from the different
      regions of Nigeria were processed for virus isolation. Infective allantoic fluids
      were tested for avian influenza viruses (AIV) and Newcastle disease virus using
      monospecific antisera. Thirty-five isolates were generated and characterized
      molecularly using the haemagglutinin gene. The molecular analysis indicated that
      different sublineages of the highly pathogenic avian influenza (HPAI) H5N1
      viruses spread throughout Nigeria. We compared the Nigerian isolates with others
      from Africa and results indicated close similarities between isolates from West
      Africa and Sudan. Some of the analysed viruses showed genetic drift, and the
      implications of these for future epidemiology and ecology of avian influenza in
      Africa require further evaluation. The spread of primary outbreaks was strongly
      linked to trade (legal and illegal), live bird markets, inappropriate disposal,
      and poorly implemented control measures. No strong correlation existed between
      wild birds and HPAI H5N1 in Nigeria.

PMID- 18631424
TI  - Hepatitis B vaccination and changes in sexual risk behaviour among men who have
      sex with men in Amsterdam.
AB  - The impact of hepatitis B vaccination in men having sex with men in Amsterdam has
      been marginal until now, possibly because of increases in sexual risk behaviour
      counterbalancing the effect of vaccination. A mathematical model is used to
      describe the hepatitis B epidemic. The model shows that, with the current
      vaccination coverage, the decrease in incidence is small in the beginning.
      However, the number of infections prevented per vaccine administered rises over
      time. Nevertheless, increased risk behaviour reduces the benefit of vaccination.
      Targeting high-risk men is more successful in reducing and containing the
      epidemic than targeting low-risk men. In conclusion, the vaccination campaign is
      effective and should be intensified. High-risk men should be targeted for
      vaccination and for risk reduction.

PMID- 18631425
TI  - Warm, wet weather associated with increased Legionnaires' disease incidence in
      The Netherlands.
AB  - It has been suggested that warm and humid weather is related to a high incidence
      of Legionnaires' disease (LD), but no data on this association existed in The
      Netherlands. The objective of this study was to investigate the short-term
      effects of the weather on LD in The Netherlands. National LD surveillance and
      meteorological data were obtained. We analysed the data using Poisson regression,
      adjusting for long-term trends, and using principal components analysis. The
      highest weekly incidence of LD occurred when the mean weekly temperature was
      +17.5 degrees C. Mean weekly relative humidity, temperature and precipitation
      intensity were associated with LD incidence in the multivariable model. Warm,
      humid and showery summer weather was found to be associated with higher incidence
      of LD in The Netherlands. These results may be used to predict an increase in the
      number of cases of LD in The Netherlands during the summer.

PMID- 18631426
TI  - A clinical prediction rule for urinary tract infections in patients with type 2
      diabetes mellitus in primary care.
AB  - We aimed to develop a prediction rule for urinary tract infections (UTIs) in
      patients with type 2 diabetes mellitus (DM2). A 12-month prospective cohort study
      was conducted in patients with DM2 aged > or = 45 years to predict the occurrence
      of recurrent UTIs in women and lower UTIs in men. Predictors for recurrent UTI in
      women (n=81, 2%) and lower UTIs in men (n=93, 3%) were age, number of general
      practitioner (GP) visits, urinary incontinence, cerebrovascular disease or
      dementia. In women, renal disease was an additional predictor. The optimism
      [corrected] corrected area under the receiver-operating curve (AUC) was 0.79 (95%
      CI 0.74-0.83) for women and 0.75 (95% CI 0.70-0.80) for men. Using a cut-off
      score of 4, women with a lower risk assignment had a probability of 0.3% for the
      outcome. For a cut-off score of 6, women with a higher risk assignment had a
      probability of 5.8%. For men these figures were 0.8 and 7.1 for a cut-off score
      of 2 and 4, respectively. Simple variables can be used for the risk
      stratification of patients.

PMID- 18631427
TI  - We are in the dark here: induction of depression- and anxiety-like behaviours in
      the diurnal fat sand rat, by short daylight or melatonin injections.
AB  - Circadian rhythms are considered an important factor in the aetiology, expression
      and treatment of major affective disorders, including seasonal affective disorder
      (SAD). However, data on the effects of daylight length manipulation or melatonin
      administration are complex. It has been suggested that since diurnal and
      nocturnal mammals differ significantly in their physiological and behavioural
      responses to daylight, diurnal rodents offer a preferable model of disorders
      related to circadian rhythms in the diurnal human. We previously found that
      diurnal fat sand rats maintained under short daylight (SD), show depression-like
      behaviour in the forced swim test (FST). The present study was designed to test
      additional behaviours related to affective disorders and study the involvement of
      melatonin in these behaviours. Sand rats were divided into short-daylight (SD, 5
      h light:19 h dark) and long-daylight (LD, 12 h light:12 h dark) groups, and
      received 100 microg melatonin or vehicle administration for 3 wk (5 h and 8.5 h
      after light onset in the LD room). Animals were then tested for reward-seeking
      behaviour (saccharin consumption), anxiety (elevated plus-maze), aggression
      (resident-intruder test), and depression-like behaviour (FST). SD or melatonin
      administration resulted in a depressed/anxious-like behavioural phenotype
      including reduced reward seeking, increased anxiety, decreased aggression and
      decreased activity in the FST, supporting the notion that in a diurnal animal,
      reduced light results in a variety of behavioural changes that may model
      depression and anxiety; and that melatonin may be a significant factor in these
      changes. We suggest that the sand rat may offer an excellent model species to
      explore the interactions between daylight, affective behaviour and the related
      underlying mechanisms.

PMID- 18631428
TI  - Examining the evidence: complementary adjunctive therapies for multiple
      sclerosis.
AB  - OBJECTIVE: The purpose of this article is to provide a comprehensive overview of
      the most frequently encountered non-conventional approaches trialed for use in
      multiple sclerosis (MS). The efficacy and safety of non-conventional approaches
      ranging from bee venom therapy (BVT) to an array of vitamins and herbal products
      were discussed and evaluated. METHODS: Relevant English-language articles were
      identified through searches of MEDLINE (1990-2006), PubMed (1999-2006), Cochrane
      (1995-2006) and Toxnet (2000-2006). Classification of available literature was
      conducted according to the evidence based guidelines established by the American
      Academy of Neurology (AAN). However, due to the non-conventional nature of these
      treatment approaches, most available literature was derived from anecdotal
      reports and suboptimal clinical studies, lacking the rigor of evidence-based
      practice. RESULTS: There is presently only marginal supportive evidence for BVT
      in MS treatment. The inability to identify and quantify the active component of
      BVT combined with the associated risk of anaphylaxis has deterred its widespread
      use. The most promising evidence comes from prophylactic daily supplementation
      with vitamin D. Despite beneficial reports regarding non-herbal supplements such
      as alpha-lipoic acid (ALA), luteolin, evening primrose oil and vitamins such as
      B12, the lack of evidence does not support their prophylactic use. DISCUSSION:
      Based on available evidence, the prophylactic use of vitamin D is a viable option
      as an adjunct to conventional medicine. Although there is a lack of conclusive
      evidence to support the use of other non-conventional treatments, patients are
      still opting to trial and bare the risks of these products which are accessible
      without the intervention of a healthcare professional. Controlled, evidence-based
      trials are essential for healthcare professionals to competently intervene and
      recommend these products.

PMID- 18631429
TI  - Microdialysis applications in neuroscience.
AB  - BACKGROUND: Microdialysis is a technique to monitor extracellular changes in
      living tissue. Substances present in the extracellular space, such as
      neurotransmitters and metabolites transported between cells and capillaries in
      the extracellular fluid (ECF), are major object. RESULTS: Since its introduction
      to the research of the nervous system, microdialysis has become a popular method
      for the measurements of brain chemistry and greatly affected in the fields of
      neuropharmacology, neuroanatomy and neurophysiology. Most of published papers
      using microdialysis have focused on the area of neuroscience, recently more
      biomedical application. CONCLUSION: In this review, we focused on cerebral
      microdialysis as a monitoring tool for physiologic and pathophysiologic changes
      in chemical processes in the brain. Then we presented the principle and various
      applications of cerebral microdialysis.

PMID- 18631431
TI  - The latest design of Ozer cervical retractor.
AB  - OBJECTIVE: Various types of retractors have been used in cervical disk
      operations. The presented device is modified from previous cervical retractor
      which uses our cervical operations routinely. The new product provides us easy
      practice during the surgery. METHOD: The retractor consists of two blades which
      are screwed on the vertebral surfaces. It also provides distraction of disk level
      during the operation. RESULTS: This retractor has been used in over 100 cases and
      there have not been any complications involving the carotid artery, trachea and
      oesophagus. CONCLUSION: New design provides a significant surgical exposure area
      under the surgical microscope. When using this retractor, there is no need to use
      a vertebral spreader because the retractor itself can be used as a vertebral
      spreader and it is possible to carry out the Smith-Robinson type fusion.

PMID- 18631430
TI  - Management of petrosal veins during microvascular decompression for trigeminal
      neuralgia.
AB  - OBJECTIVE: Venous compression might be the main cause of incomplete decompression
      and symptom recurrence after microvascular decompression (MVD) in patients with
      trigeminal neuralgia. Although it can be killed in most cases, cutting the vein
      sometimes has the potential risk arising from venous congestion. To maneuver the
      vein safely, we introduced a temporary occlusion test of the vein. METHODS: Among
      407 consecutive MVD cases, 48 (11.8%) offending and 157 block veins were
      encountered. The vein was cut directly in 147 (71.7%). Owing to the potential
      risk following killing of the vein, 58 (28.3%) patients underwent venous
      occlusion test with neurophysiologic monitoring during the operation. The
      temporal occlusion should be ceased immediately as soon as any changes in
      brainstem auditory evoked potential (BAEP) or trigeminal evoked potential (TEP)
      wave figuration turn up; otherwise, it would last for 15 minutes. RESULTS: The
      occlusion test was negative in 53 (91.4%), while positive in five patients
      (8.6%). According to the results, we cut the vein in test-negative patients,
      which made the operation easy and offered a satisfactory decompression. Among the
      five positive cases, the vein was finally saved in two and cut in three cases.
      Yet, all the three patients developed a severe ipsilateral cerebellar edema and
      brainstem shift after the vein was sacrificed. Despite those patients were
      reoperated on immediately for posterior fossa decompression, they remained
      equilibrium disorder with numbness in ipsilateral face and mind hemiparesis in
      contralateral extremities post-operatively. The residual two patients had an
      incomplete pain relief. CONCLUSION: This venous occlusion test could help the
      surgeon in making a right decision before manipulation of the petrosal veins
      during MVD.

PMID- 18631432
TI  - Post-operative changes of cerebral circulation and metabolism in the acute stage
      of low-grade aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Pre- and post-operative cerebral circulation and metabolism were
      evaluated in patients with low-grade acute aneurysmal subarachnoid hemorrhage
      (SAH) who underwent early surgery to investigate the effects on brain
      dysfunction. METHODS: Positron emission tomography (PET) was performed to measure
      the regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen
      (CMRO2), oxygen extraction fraction (OEF) and cerebral blood volume in four
      patients (one male and three females, mean age: 60.3 years) with low-grade SAH
      within 30 hours of onset. Post-operative PET was performed on the seventh post
      operative day. No patient suffered clinical deterioration during the study. Pre
      operative PET scans demonstrated significant global reduction of CBF and CMRO2,
      compared to 16 normal control subjects, and no significant change in OEF. CBF and
      CMRO2 reduction post-operatively improved to the normal control values. Post
      operative OEF was significantly increased compared to the normal control value.
      CONCLUSIONS: Patients with low-grade SAH have impairment of cerebral circulation
      and metabolism in the acute period, which improves after surgery. Early surgery
      for low-grade SAH, necessary to avoid rerupture of the aneurysm, did not worsen
      the impairment of cerebral circulation and metabolism. However, measures to
      protect the brain from perioperative damage are necessary to achieve the optimum
      outcome.

PMID- 18631433
TI  - Cortical responses to Mozart's sonata enhance spatial-reasoning ability.
AB  - OBJECTIVE: In this study, we examined the effects of Mozart's music on spatial
      reasoning ability by near-infrared spectroscopy (NIRS). METHODS: The subjects
      comprised five males and five females (aged 25-35 years). They were administered
      the seven original core subtests of the Japanese version of the Tanaka B-type
      intelligence test, which includes a spatial-reasoning subtest. We used three
      different music conditions: Mozart's sonata (K. 448), Beethoven and a silent
      control condition. Moreover, we used optical topography to assess the effects of
      music on brain function with a spatial-reasoning subtest. RESULTS: We found that
      exposure to Mozart's sonata enhanced cognitive performance in intelligence tests
      when compared with results obtained upon exposure to Beethoven or silence. In
      addition to the expected temporal cortex activation, we report dramatic results
      revealing differences in activation in the dorsolateral prefrontal cortex and the
      occipital cortex, both of which are expected to be important for spatial-temporal
      reasoning. DISCUSSION: We suggest the possibility of a direct priming effect
      being responsible for preferential activation, and open the door to understanding
      the potential effects of Mozart's music.

PMID- 18631434
TI  - Major potential of diet treatment for type 2 diabetes.

PMID- 18631435
TI  - Can OCT serve as a surrogate for visual acuity in eyes with DME?

PMID- 18631436
TI  - Genetic susceptibility of diabetic retinopathy.
AB  - Diabetes continues to be a major source of -morbidity and mortality among working
      age adults nationally and internationally. The microvascular complications of
      diabetes, including diabetic retinopathy, account for a major proportion of
      disease-associated morbidity and likely contribute to macrovascular
      complications. Although glycemic control contributes to -susceptibility for
      diabetic complications, some people with strict control develop these
      complications, whereas -others with poor control remain complication free. This
      suggests a genetic contribution to disease development. Although many genes and
      proteins of vascular growth have been studied in association with diabetic
      retinopathy, no definitive major predisposing genes or functional consequences of
      genetic variants have been identified for microvascular complications of the
      disease. In this article, we review the studies done on candidate genes.

PMID- 18631438
TI  - Does pregnancy accelerate the rate of progression of diabetic retinopathy?: an
      update.
AB  - Pregnancy may be associated with several ocular changes, including the
      development of new ocular conditions or modifications of existing conditions. The
      most common ocular condition modified by pregnancy is diabetic retinopathy.
      Pregnancy is associated with an increased risk of development and progression of
      diabetic retinopathy. The factors associated with its progression include the
      pregnant state itself, duration of diabetes, amount of retinopathy at conception,
      blood glucose control, and the presence of coexisting hypertension. Although the
      rate of regression of diabetic retinopathy at the end of pregnancy or the
      postpartum period is high, careful monitoring of these patients is necessary to
      optimize the vision and pregnancy outcomes.

PMID- 18631437
TI  - Novel potential mechanisms for diabetic macular edema: leveraging new
      investigational approaches.
AB  - This article evaluates the current knowledge of the molecular mechanisms by which
      diabetes ocular and systemic inflammation induce breakdown of the blood-retinal
      barrier resulting in macular edema. We also summarize the relationship between
      molecular targets and the use of therapeutic inhibitors in preclinical studies
      and clinical trials. Further studies are needed to understand the regulation of
      normal blood-retinal barrier physiology and the relationship between events in
      animal models of diabetic retinopathy and humans with diabetes.

PMID- 18631439
TI  - Postpartum diabetes screening for women with gestational diabetes: are we missing
      an opportunity for prevention?

PMID- 18631440
TI  - Breast-feeding and diabetes: long-term impact on mothers and their infants.
AB  - In the general population, breast-feeding is associated with a reduced risk of
      the offspring being overweight later in life by 22% to 24% across the age
      spectrum, from preschool children to adults. There is a dose-response gradient
      with increasing duration of breast-feeding, and lowest risk with prolonged,
      exclusive breast-feeding. Breast-feeding has been shown to slow infant growth up
      to 2 years of age. By contrast, the scientific evidence is inconclusive about
      whether breast-feeding protects against the onset of overweight and subsequent
      development of type 2 diabetes among offspring whose mothers had diabetes during
      pregnancy. Moreover, evidence is insufficient to determine if lactation protects
      against development of type 2 diabetes later in life in women with a diabetes
      history during pregnancy. Given the paucity of the evidence and equivocal
      findings about the long-term effects of breast-feeding on future health of women
      with diabetes during pregnancy and their infants, further research is
      recommended.

PMID- 18631441
TI  - GDM: postpartum management to reduce long-term risks.
AB  - Diabetes prevalence has increased dramatically, with 1.3 million new cases
      diagnosed annually. Women with gestational diabetes mellitus (GDM) are at
      increased risk for developing overt diabetes later in life. In addition, their
      offspring, exposed to the diabetic environment in utero, are also at increased
      risk for developing obesity, glucose intolerance, and type 2 diabetes later in
      life. Diabetes begets diabetes. The GDM diagnosis provides the medical community
      with an opportunity to intervene with strategies to prevent and/or delay the
      onset of diabetes and its associated long-term complications. This article
      reviews the roles of medical nutrition therapy, physical activity, and
      pharmacotherapy in preventing type 2 diabetes in women with a GDM history.

PMID- 18631442
TI  - Preconception planning: are we making progress?
AB  - According to the American Diabetes Association, unplanned pregnancies in women
      with diabetes could lead to abnormal metabolic control, which causes fetal and
      maternal complications. Preconception planning can decrease these risks. This
      article reports on the progress in preconception planning over the past 2 years.

PMID- 18631443
TI  - The role of exercise in the prevention and treatment of gestational diabetes
      mellitus.
AB  - Gestational diabetes mellitus (GDM) is a form of diabetes first diagnosed during
      pregnancy, usually between 24 and 28 weeks. Currently, management for women with
      GDM consists of medical nutrition therapy with adjunctive exercise for at least
      30 minutes/day. Patients who fail to maintain glycemic goals through diet and
      exercise therapy are given insulin injections. Several epidemiological studies
      have suggested a robust link between physical activity and reduced risk of GDM;
      however, researchers have been unable to suggest a cost-effective, easily
      accessible, evidence-based program with guidelines for frequency, intensity,
      duration, and type of activity to prevent the incidence of GDM in sedentary, at
      risk populations. True effectiveness of specific structured exercise programs
      remains untapped in GDM prevention and treatment, and many well-controlled
      exercise studies are warranted.

PMID- 18631444
TI  - Benefits of simultaneous islet-kidney transplantation versus simultaneous
      pancreas-kidney transplantation.

PMID- 18631445
TI  - Glucose metabolism after pancreas-kidney transplantation.
AB  - Simultaneous pancreas-kidney (SPK) transplantation is a promising treatment
      option for patients with type 1 diabetes and end-stage renal disease. Most of
      these patients can achieve normalization of glucose and hemoglobin A(1c) levels.
      Patient and graft survival continues to improve; however, defects in beta-cell
      function and insulin resistance can be seen over time after transplant. Various
      methods can be used to assess the SPK recipient for the development of
      hyperglycemia and graft dysfunction, with treatment aimed at minimizing
      diabetogenic immunosuppression, using agents that may preserve beta-cell
      function, and improving insulin resistance.

PMID- 18631446
TI  - Hypoglycemia following pancreas transplantation.
AB  - Mild symptoms of hypoglycemia in individuals with type 1 diabetes who have
      undergone pancreas transplantation are common, but biochemical evidence of
      hypoglycemia in these individuals often remains scant. Rarely, more overt cases
      with profound neuroglycopenic symptoms and documented hypoglycemia after
      transplantation have been described. Although the diagnosis of hypoglycemia in
      most cases of adrenergic symptoms alone, without documented hypoglycemia, remains
      questionable and likely not clinically significant, several potential etiologies
      have been identified in the more severe cases. This article reports a case with
      severe hypoglycemia after pancreas transplantation for type 1 diabetes, reviews
      several potential mechanisms underlying pancreas allograft-associated
      hypoglycemia, and discusses current treatment strategies for minimizing
      symptomatic hypoglycemia after transplant.

PMID- 18631447
TI  - Current challenges in islet transplantation.
AB  - Allogeneic islet transplantation is becoming a treatment option for patients with
      unstable type 1 diabetes mellitus (T1DM). Around 80% of the islet recipients
      achieve insulin independence after one or two islet infusions under "Edmonton
      like" immunosuppressive protocol, but only 10% will remain insulin independent
      over the long term. Islet transplantation leads to glucose stabilization, and
      severe hypoglycemia is prevented even in patients back on insulin injections.
      Thus, islet transplantation has achieved the proposed targets in patients with
      unstable T1DM: normalizing blood glucose and hemoglobin A(1c), preventing severe
      hypoglycemic episodes, and improving quality of life. The current aims of islet
      transplantation programs are to maintain the success achieved and to overcome
      remaining obstacles and limitations.

PMID- 18631448
TI  - ROS eliminate danger.
AB  - Necrotic cells release HMGB1 as a danger signal to activate the immune system. In
      this issue of Immunity, Kazama et al. (2008) identify a mechanism that determines
      whether HMGB1 is tolerogenic or immunogenic.

PMID- 18631449
TI  - gammadelta T cell selection: is anyone useless?
AB  - In this issue of Immunity, a study by Jensen et al. (2008) suggests that T cell
      receptor engagement during development affects gammadelta T cell polarization
      toward either interferon-gamma or interleukin-17 production. This might underlie
      their unique innate ability to regulate inflammation.

PMID- 18631450
TI  - Regulatory T cells and inflammation: better late than never.
AB  - In this issue of Immunity, Curotto de Lafaille et al. (2008) show that adaptive T
      regulatory cells control airway inflammation and that it is when they are
      generated that determines whether they function during acute or chronic
      inflammation.

PMID- 18631451
TI  - With a little help from their friends: interleukin-21, T cells, and B cells.
AB  - T follicular cells help B cells generate high-affinity antibodies. Two papers in
      this issue of Immunity (Nurieva et al., 2008, and Vogelzang et al., 2008) have
      identified a role for interleukin-21 in the development of these specialized
      cells and highlight questions about how this dedicated population is generated.

PMID- 18631452
TI  - Bottom up: a modular view of immunology.
AB  - In this issue of Immunity, Chaussabel et al. (2008) apply an inductive approach
      to pathway discovery identifying modular units that govern human immune biology.

PMID- 18631453
TI  - When signaling pathways collide: positive and negative regulation of toll-like
      receptor signal transduction.
AB  - Toll-like receptor (TLR) signaling is subjected to crosstalk from other signals,
      with a resulting positive or negative effect. There is complex crosstalk between
      the NLR family of immune-regulatory molecules and TLRs, and C-type lectin
      receptors such as Dectin-1 synergize with TLR2 via the tyrosine kinase Syk.
      Bruton's tyrosine kinase plays an important positive role in TLR signaling,
      whereas the TAM family of receptor tyrosine kinases is inhibitory. The tyrosine
      phosphatase SHP1 has been shown to positively regulate induction of interferon
      beta, whereas SHP2 inhibits the kinase TBK1, limiting this response. K63-linked
      polyubiquination has also been shown to be critical for the initiation of TLR
      signaling. Finally, glucocorticoids affect TLR signaling by inducing the
      phosphatase MKP1 and inhibiting TBK1 activation. These recent findings emphasize
      the importance of considering TLR signaling in the context of other signaling
      pathways, as is likely to occur in vivo during infection and inflammation.

PMID- 18631456
TI  - The organization of the central nervous connectives in Anodonta cygnea (Linnaeus)
      (Mollusca : Eulamellibranchia).
AB  - The cerebro-visceral connective of Anodonta cygnea comprises a non-cellular
      neural lamella, a few randomly distributed glial elements, and axons, together
      with an extensive extracellular system. The axons are relatively small, the
      majority being less than 2.0 micro in diameter. The neural lamella is underlaid
      by a thin layer of peripheral glial processes. The membranes of the proximate
      glial processes do not reveal any junctional complexes at this level. In addition
      to glycogen and fat deposits, the glial cytoplasm contains abundant 'glial
      granules' which in histochemical tests react like mucoproteins. The extracellular
      space appears to be freely accessible, for apart from the neural lamella no other
      visible structures are interposed between it and the fluid surrounding the
      connective. These structural findings are discussed in relation to the available
      evidence concerning the ability of axons to function in preparations bathed in
      low-sodium media.

PMID- 18631457
TI  - The organization of ampullary sense organs in the electric fish, Gymnarchus
      niloticus.
AB  - Three types (A, B, and C) of ampullary sense organs occur in the skin of
      Gymnarchus niloticus. In type A the ampulla is connected to the surface of the
      skin by an open duct whereas in B and C organs it is closed, though overlain by
      specialized epidermal cells. In each case the receptor cell surface in contact
      with the ampullary lumen bears microvilli; these are more highly developed in B
      and C organs than in type A. Fine structural observations are consistent with the
      view that the organs are electric receptors of three different types.

PMID- 18631458
TI  - Glutaraldehyde fixation of central nervous tissue: an electron microscopic
      evaluation in the isolated rabbit retina.
AB  - The isolated rabbit retina was studied electron microscopically after fixation
      with a 3% solution of glutaraldehyde in a 0.05 M Sorensen's phosphate buffer. In
      radial sections, the inner segments, nuclei, and synapses of the photoreceptor
      cells seemed similar in size to those from retinas that had been fixed in an
      isotonic solution containing 1 % crystalline osmium tetroxide in the incubating
      medium used for the isolation procedure. However, when the number of comparable
      structures was greatly increased by viewing them in tangential sections, the
      cellular shrinkage and mitochondrial swelling produced by this widely used,
      hypertonic, glutaraldehyde fixative were obvious.

PMID- 18631454
TI  - Induction of immunological tolerance by apoptotic cells requires caspase
      dependent oxidation of high-mobility group box-1 protein.
AB  - The mammalian immune system discriminates between modes of cell death; necrosis
      often results in inflammation and adaptive immunity, whereas apoptosis tends to
      be anti-inflammatory and promote immune tolerance. We have examined apoptosis for
      the features responsible for tolerance; specifically, we looked at the roles of
      caspases and mitochondria. Our results show that caspase activation targeted the
      mitochondria to produce reactive oxygen species (ROS), which were critical to
      tolerance induction by apoptotic cells. ROS oxidized the potential danger signal
      high-mobility group box-1 protein (HMGB1) released from dying cells and thereby
      neutralized its stimulatory activity. Apoptotic cells failed to induce tolerance
      and instead stimulated immune responses by scavenging or by mutating a
      mitochondrial caspase target protein when ROS activity was prohibited. Similarly,
      blocking sites of oxidation in HMGB1 prevented tolerance induction by apoptotic
      cells. These results suggest that caspase-orchestrated mitochondrial events
      determine the impact of apoptotic cells on the immune response.

PMID- 18631459
TI  - Histological techniques for study of photoreceptor orientation.
AB  - An histological method for the study of photoreceptor orientation in primate eyes
      is described. To preserve photoreceptor orientation it is necessary to protect
      the fragile rod and cone outer segments to the maximum extent possible from
      mechanical deformation and from injury by solvent extraction. To prevent
      mechanical deformation the eyes are freeze-dried and embedded in plastic with or
      without prior vapor fixation. Solvent extraction from the lipid-rich outer
      segment is limited by avoidance or restriction of organic solvents. When large
      segments of primate eyes are so treated, it is possible to section the plastic
      blocks along the visual axis, polish the block surface, and view photoreceptor
      orientation by epi-illumination microscopy. In such specimens a differential
      orientation of photoreceptors exists with the long axis of photoreceptor inner
      and outer segments in line with incoming light rays.

PMID- 18631455
TI  - A modular analysis framework for blood genomics studies: application to systemic
      lupus erythematosus.
AB  - The analysis of patient blood transcriptional profiles offers a means to
      investigate the immunological mechanisms relevant to human diseases on a genome
      wide scale. In addition, such studies provide a basis for the discovery of
      clinically relevant biomarker signatures. We designed a strategy for microarray
      analysis that is based on the identification of transcriptional modules formed by
      genes coordinately expressed in multiple disease data sets. Mapping changes in
      gene expression at the module level generated disease-specific transcriptional
      fingerprints that provide a stable framework for the visualization and functional
      interpretation of microarray data. These transcriptional modules were used as a
      basis for the selection of biomarkers and the development of a multivariate
      transcriptional indicator of disease progression in patients with systemic lupus
      erythematosus. Thus, this work describes the implementation and application of a
      methodology designed to support systems-scale analysis of the human immune system
      in translational research settings.

PMID- 18631460
TI  - An electron microscope study of the influence of divalent ions on myosin filament
      formation in chicken gizzard extracts and homogenates.
AB  - Myosin as well as actin filaments could be seen in negatively stained
      preparations of fresh chicken gizzard homogenized in buffered KCI (I=0.12, pH
      6.85), in a 1 : 1 ratio. Myosin filaments were also present when homogenates were
      diluted (1 : 9) with solutions containing additional Mg(++) and ATP provided
      naturally occurring traces of Ca(++) had not been chelated with EGTA. There were
      no myosin filaments when Mg(++), ATP, Ca(++) or Ca(++) +ATP were added
      respectively to the diluent. It is suggested that in vivo in relaxed muscles
      myosin is present in dimers, and only aggregates into filaments at the onset of
      contraction when Ca(++) are released.

PMID- 18631461
TI  - A comparison of the distribution of enzymatically and non-enzymatically produced
      lead phosphate in insect flight muscle.
AB  - Lead phosphate precipitates were produced in indirect flight muscles of Phormia
      regina by sequential incubation in solutions containing lead and inorganic
      phosphate and their distribution was compared with those produced by ATP
      hydrolysis in the presence of lead. Enzymatically produced precipitates were
      associated almost exclusively with thick filaments. Non-enzymatically produced
      precipitates were associated with thick filaments but were also found associated
      with thin filaments in significant numbers.

PMID- 18631462
TI  - The ultrastructure of the oenocytes in the molt/intermolt cycle of an insect.
AB  - The structure and development of the permanent oenocytes of Calpodes ethlius
      (Lepidoptera, Hesperiidae) are described. There are three sorts of oenocyte. The
      permanent oenocytes are arranged ventral to the last two pairs of spiracles on
      abdominal segments 7 and 8 in four clusters of about 45 cells each. The molt
      cycle oenocytes are ventral to the other spiracles and only enlarge at molting.
      The subdermal oenocytes differentiate from the epidermis in large numbers shortly
      before pupation. The permanent oenocytes are large polyploid cells characterized
      by a cytoplasm of densely packed smooth tubular endoplasmic reticulum, and a
      plasma membrane invaginated in a meshwork of tubes ending in a reticular layer
      about 12 micro below the surface. There are two sorts of Golgi complex, one small
      and of conventional form, the other composed of clouds of microvesicles. 'Dense
      bodies', believed to belong to the microbody class of organelles, arise directly
      from the STER. There is a variety of membranous and 'crystalline' inclusions. The
      formation of isolation membranes from the tubular endoplasmic reticulum, and the
      origin of isolation bodies and autophagic vacuoles are described. Some autophagy
      takes place at all times in the molt/intermolt cycle, but there are phases of
      massive autophagy before the 4th-5th molt and the 5th-pupal molt. These phases
      coincide with pinocytosis of blood proteins and overlap with or are followed by
      phases of nuclear replication, RNA synthesis (ribosomes) and ER regeneration.
      Nuclear blebbing occurs before pupation. The morphology of the oenocytes is most
      like that of vertebrate cells engaged in steroid hormone synthesis. It is pointed
      out that the oenocytes rather than the prothoracic glands could be the source of
      ecdysone and the stimulus for molting.

PMID- 18631463
TI  - The architecture of the accessory reproductive glands of the male desert locust:
      1: types of glands and their secretions.
AB  - The accessory reproductive glands of the male desert locust were studied by
      histological, histochemical, and phase-contrast techniques. It was found that the
      characteristics of the glandular epithelium and their corresponding secretions
      permit the division of the accessory glands into nine distinct types. Three types
      produce coarsely granular mucopolysaccharide secretions (glands 1, 11, and 12);
      three types produce finely fibrous mucopolysaccharide secretions (glands 2, 4,
      and 7-10, 13-15); one type produces a globular mucopolysaccharide or
      mucoproteinaceous secretion (gland 6); one type produces an acidic lipoprotein
      complex (glands 3 and 5); and one is the functional seminal vesicle (gland 16).
      Consequently, the various secretions are separated as a result of a vertical
      segregatign of the various cell types that are responsible for glandular
      activity.

PMID- 18631464
TI  - Pore canal shape related to molecular architecture of arthropod cuticle.
AB  - The rotating structure of pore canals is interpreted in terms of the Bouligand
      model of rotating layers of chitin-protein microfibrils, and the daily growth
      layer system in insects. Crustacean and arachnid examples are also used. Pore
      canals are flattened into ribbons by neighbouring microfibrils. The ribbons run
      straight when traversing layers with preferred microfibril orientation, but
      rotate in phase through lamellate layers in which the layers of microfibrils also
      rotate. Oblique sections of models show that the parabolic artefact derived from
      microfibrils, and the parabolic arcs of pore canals seen as crescents in section,
      only superimpose, as they do in actual sections, when both systems have the same
      sense of rotation. Pore canal rotation may be determined by chitin-protein
      architecture.

PMID- 18631466
TI  - The structure of the eye of Ligia oceanica L.
AB  - There are eight retinula cells in each ommatidium. Two of these cells are half
      the size of the others, and there is a small basal cell with large vesicles in
      its cytoplasm but no rhabdomere. The rbabdomeres are separate and the cytoplasm
      of the basal cell extends into the space between them at the central end. The
      rhabdomere tubules are regularly arranged at the periphery and irregular at the
      central end. The extent of irregular arrangement is increased if animal is kept
      in dark. There are eight axons from each ommatidium.

PMID- 18631465
TI  - A quantitative morphological study of osmotically induced swelling and shrinkage
      in nervous tissue.
AB  - The rabbit retina was used to study, in vitro, the responses of central nervous
      tissue to changes in extracellular osmolarity. After isolation, retinas were
      incubated in either hypertonic or hypotonic medium containing 80 milliosmols more
      or 80 milliosmols less sodium chloride than the isotonic control medium. After
      fixation and embedding, comparable areas of each retina were sectioned and
      studied with the phase and electron microscopes. The diameters of receptor cell
      inner segments, synapses, nuclei, and mitochondria were measured on micrographs;
      mean nuclear areas and volumes were calculated. Cutouts from micrographs also
      provided areas and volumes of the receptor cell nucleus and its 'surround' of
      axons, dendrites, glial processes, and extracellular space. In general,
      hypertonic incubation produced decreases in the linear dimensions, areas, and
      volumes of the receptor cell, its nucleus, and its mitochondria that were
      consistent with their behaviour as osmometers. After hypotonic incubation, the
      increases in the diameters of inner segments, synapses, and mitochondria were in
      the predicted range. The increases for the nuclei themselves, and the nuclei and
      their 'surround' were less than expected. This may have been due to the failure
      of the preparative techniques to maintain the swollen state of these larger
      structures.

PMID- 18631467
TI  - Fine structure of red and white muscle fibers and their neuromuscular junctions
      in the snake fish (Ophiocephalus argus).
AB  - The snake fish red muscle fiber, consisting of only polygonal myofibrils, has a
      smaller diameter and more abundant mitochondria and glycogen granules than the
      white fiber, which consists of ribbon-like and polygonal myofibrils. M bands,
      ordered Z bands, well developed triads, and multiple neuromuscular junctions of
      'en grappe' type, which lack postsynaptic infoldings, occur in both types of
      fiber. The density of neuromuscular junctions is greater in the red fiber than in
      the white fiber. These results indicate that the both types of fiber of the snake
      fish are morphologically different from the slow and twitch fibers of the frog.

PMID- 18631468
TI  - A structural basis for fluid secretion by malpighian tubules.
AB  - The Malpighian tubules of Calliphora are described, emphasizing the possible role
      of surface specializations in solute-linked water transport. The tubules are
      composed of two cell types, primary and stellate, intermingling along the tubule
      length. The primary cells have long narrow basal infoldings and a microvillate
      luminal border, both intimately associated with mitochondria. The stellate cells
      have shorter and wider basal infoldings and their apical microvilli do not
      contain mitochondria. Application of the standing gradient hypothesis to this
      sytem provides a model for urine formation in which the local gradients for
      osmotic water flow occur within the long narrow channels of the basal infolds and
      microvilli of the primary cells. Stellate cells may modify the initial secretion
      by reabsorbing sodium.

PMID- 18631469
TI  - The ultrastructure of a pheromone-secreting gland in the male scorpion-fly
      Harpobittacus Australis (Bittacidae: Mecoptera).
AB  - The eversible vesicles of the sex pheromone glands consist of three cell types,
      secreting the cuticle, the duct and the pheromone, respectively. Each pheromone
      secreting cell has an end apparatus, bounded by microvilli and lined by a
      granular mass, that is penetrated by remarkable elongate filaments extending far
      up into the secretory duct. Vesicles containing secretion or secretion precursors
      abound. The possible role is discussed of the various organelles in the
      elaboration and transport of the pheromone.

PMID- 18631470
TI  - Fine structural organization of the spermatheca in the cockroach, Periplaneta
      americana.
AB  - The detailed structure of the cockroach spermatheca is described and discussed
      firstly as an example of an insect integumentary gland, and secondly, from the
      standpoint of its role in reproduction. The gland comprises a cortical rank of
      separate secretory units, each associated with an epithelial duct cell
      responsible for receiving secreted materials and transporting them through the
      cuticular intima lining the reproductive tract. Secretory activity is cyclic, and
      the probable mode of elaboration and release of secretory material is described,
      together with the fine structure of the markedly differing intimas associated
      respectively with the glandular and conducting units.

PMID- 18631471
TI  - The architecture of the accessory reproductive glands of the male desert locust
      2: Microtubular structures.
AB  - Cytoplasmic microtubules are distributed widely in the mature accessory
      reproductive glands of the male desert locust. They are not concentrated in any
      particular region of the cytoplasm, but they appear to be closely associated with
      mitochondria and the Golgi apparatus. The individual microtubules have a helical
      configuration, and they are often congregated in bundles. It is suggested that
      the microtubules arise from Golgi regions, and that they function as a
      scaffolding for the maintenance of the shape of the glandular cells.

PMID- 18631472
TI  - Statocysts of medusae and evolution of stereocilia.
AB  - Ectodermal sensory cells of the statolith each bear one nonmotile kinocilium, and
      in some hydromedusae bear stereocilia which are defined as distinct from
      microvilli by having fibrillar rootlets. The progressive elaboration of
      stereocilia can be traced. A hypothesis in which jellyfish statocysts evolve from
      vibration receptors avoids the difficulty of the uselessness of incipient gravity
      organs. Comparative study suggests that the kinocilium or its basal body is the
      transducer.

PMID- 18631473
TI  - Molecular architecture of adult locust cuticle at the electron microscope level.
AB  - It is shown that locust adult endocuticle consists of a daily alternation of two
      types of chitin-protein architecture: (i) non-lamellate day layers with
      microfibrils oriented in a preferred direction, traversed by pore canals whose
      shape resembles an untwisted ribbon, (ii) lamellate night layers with
      helicoidally oriented microfibrils traversed by pore canals shaped like regularly
      twisted ribbons. Uncoupling the circadian clock which normally controls the
      timing of these two types leads to growth of cuticles which are organized like
      one or the other throughout. We can thus experimentally change the architecture
      of the microfibrils which in turn changes the pore canals.

PMID- 18631474
TI  - The structure and development of a surface pattern on the cuticle of the green
      vegetable bug Nezara viridula.
AB  - Adult Nezara possess an area of cuticle on the metathoracic sternite with a
      surface pattern of minute mushroom-like projections. The surface pattern is
      formed by two types of cell, one forming projections and the other depressions.
      The surface pattern is largely determined before epicuticle deposition by
      deformation of the epidermal surface. This is brought about by interactions
      between the moulting fluid secretions and the cells. Maintenance of shape of the
      cells may be associated with the presence of oriented cytoplasmic microtubules.
      The mushroom area may function as an external reservoir causing retarded
      evaporation of defensive secretions.

PMID- 18631475
TI  - Neurofilaments and microtubules in anterior horn cells of the rat.
AB  - Dendrites arising from the larger nerve cells in the anterior horn contain
      fascicles of neurofilaments in addition to the usual dendritic components From a
      comparison of neurofilaments and microtubules, and their respective subunits it
      is concluded that direct interconversion between them is improbable In transverse
      section the wall of the neurofilament is composed of 4-6 circular densities about
      30 A in diameter Short spokelike side arms project from the circular densities
      into the surrounding cottony matrix in which the filaments are embedded.

PMID- 18631476
TI  - Some aspects of the gross and fine structure of the amphibian papilla in the
      labyrinth of the newt, Triturus cristatus.
AB  - Each receptor cell in the sensory macula bears a number of stereocilia and one
      peripherally located kinocilium; in the two halves of the macula, the kinocilia
      lie on opposite sides of their associated stereocilia. The morphological axes of
      the receptor cells are approximately parallel to the long axis of the papilla.
      The gelatinous cupula overlying the macula extends almost to the opposite wall of
      the papilla. These structural features are discussed in connection with both the
      proposed function of the papilla as a vibration detector and the possible
      evolutionary relationships with other acousticolateralis receptors.

PMID- 18631477
TI  - The envelopes of the nervous system of pseudoscorpions and scorpions.
AB  - The present paper demonstrates that in pseudoscorpions and scorpions a compact
      collagen sheath consisting of fibrils with a 720 A period embedded in a neutral
      mucopolysaccharide surrounds the nervous system. The same material makes up the
      trabeculae running into the nervous elements of the ganglia and nerves. Both
      structures are separated from the neurons and their fibres by entire glial cells
      or by their processes. The neural lamella is surrounded by a thin and continuous
      wall of cells forming a storage-epithelium. Amoebocytes are able to circulate
      between the collagen fibrils of the neural lamella.

PMID- 18631478
TI  - The eye of Dytiscus (Coleoptera).
AB  - The eye of Dytiscus (Coleoptera) has rhabdomeres at three different levels. The
      crystalline threads stretch from the ends of the crystalline cones only as far as
      the distal layer of rhabdomeres. There is one distal rhabdomere per ommatidium,
      and in this system the ommatidia are anatomically separate. Between the distal
      rhabdomere and the rhabdomeres of the next six retinula cells is a wide clear
      zone in which light entering by one facet could possibly reach deep rhabdomeres
      of a different ommatidium. Of the six proximal rhabdomeres, four have rhabdomere
      tubules which lie horizontal with reference to the normal posture, the other two
      having vertically oriented tubules. The eighth cell, with nucleus near the
      basement membrane, has a small rhabdomere. All eight retinula cells have axons
      and there is no other class of axons in the eye.

PMID- 18631479
TI  - The fine structure of haltere sensilla in the blowfly Calliphora erythrocephala
      (Meig.), with scanning electron microscopic observations on the haltere surface.
AB  - The dipteran haltere incorporates large numbers of regularly disposed
      mechanoreceptors providing the sensory input enabling the vibrating haltere to
      function as a gyroscopic organ of equilibrium. Campaniform sensilla of the basal
      and scapal regions have been investigated by light and transmission electron
      microscopy, and these observations are augmented by scanning electron studies of
      the cuticle overlying the groups of sensilla. Each sensillum possesses a
      specialized fan-shaped terminal containing a complex and ordered association of
      microtubules and filaments. The transmission of stress to this region via the
      cuticle, and its possible role in transduction is considered. The fine structure
      of apical and basal sections of the distal sensory process and associated sheath
      cells is described; the functional significance of the distribution of
      mitochondria and other components is discussed. The organization of haltere
      chordotonal sensilla is described briefly, and compared with other
      mechanoreceptors with particular reference to microtubules and scolopale
      structures.

PMID- 18631480
TI  - The fine structure of pigeon breast muscle.
AB  - The pectoralis major muscle of the pigeon is composed of two types of muscle
      fibre. In the Type I fibres, the myofibrils are closely packed and there are few
      mitochondria. The myofibrils in the Type II fibres are separated by numerous
      columns of large mitochondria and lipid droplets. The membrane systems of the two
      types of fibre are similar. The triads occur at the Z-line; the sarcoplasmic
      reticulum is in the form of large terminal cisternae which are joined by narrow
      longitudinal tubules to a broad central cisterna. The value of morphological
      criteria in the classification of muscle fibres is discussed.

PMID- 18631481
TI  - The effect of antidiuretic hormone on avian salt gland function.
AB  - The effect of vasopressin (ADH) on the extrarenal secretory pattern from normal
      and contralateral chronically denervated salt glands in the conscious salt-loaded
      domestic goose was examined. ADH pretreatment reduced the total outputs and
      initial rates of water and cation concentrations 30-80% from both type glands.
      ADH also enhanced the onset time of secretion from the denervated glands and
      reduced the sodium concentration from both type glands. Both untreated and ADH
      treated animals exhibited an increased output of water and cations from the
      denervated glands as compared with control glands. ADH caused no noticeable
      effect on this phenomenon.

PMID- 18631482
TI  - The structure and function of the cephalic organ of a nemertine Lineus ruber.
AB  - The structure of the organ has been studied by light- and electron-microscopy.
      The organ is composed of both glandular and neural cells. The glandular cells
      pour their secretions into a ciliated tube which connects the organ with the
      external medium. Within the organ lobule, the tube forms three right-angled bends
      and is divided longitudinally into in going and outgoing channels by the adhesion
      of two groups of dilated cilia arising from opposite sides of the canal
      epithelium. Neural elements, backing the ciliated cells, constitute a possible
      neural chain to the central nervous system. The function of the organ is
      discussed.

PMID- 18631483
TI  - The ultrastructure of the osmeterium and the nature of its secretion in Papilio
      larvae (lepidoptera).
AB  - Two main cell types constitute the defensive osmeterium gland of Papilio larvae.
      Ellipsoid gland cells have an extensively infolded basal plasma membrane,
      abundant ribosomes and whorls of smooth endoplasmic reticulum. The apical plasma
      membrane bears long microvilli extending into a mass of granular material
      containing electron-lucid cavities. Tangential slits occur in the epicuticle.
      Tubular arm cells contain heterogeneous, electron-dense inclusions, extensively
      branched nuclei and large mitochondria sometimes distended with electron-dense
      material. The apical plasma membrane bears short microvilli. The inner, dense
      epicuticle forms a complex ramifying system. The two-phase defensive fluid
      consists mainly of water, 2-methyl propionic acid, and 2-methyl butyric acid.

PMID- 18631484
TI  - The localization of a peroxidase associated with hard cuticle formation in an
      insect, Calpodes ethlius stoll, Lepidoptera, Hesperiidae.
AB  - The distribution of a peroxidase associated with the formation of hard cuticle
      has been studied in developing larvae of Calpodes ethlius. It occurs in granules
      in several cell types but is most easily observed in the cells making the proleg
      spines at the 4th to 5th molt. Light microscopy shows peroxidase in numerous
      granules about 0.5micro in diameter at the time the cuticle of the spine shaft is
      being deposited. Electron microscopy shows these granules to be multivesicular
      bodies with peroxidase in the matrix. Peroxidase is also found in cisternae of
      the rough ER near Golgi complexes, in vesicles of Golgi complexes and in the
      secretory vesicles which discharge to make cuticle at the apical surface. The
      cuticle above the plasma membrane where peroxidase is being deposited reacts with
      DAB in the absence of hydrogen peroxide. Presumably this cuticle has been
      'peroxidized' as a first stage in stabilization by cross-linking. Some of the
      peroxidase secreted at the apical surface is pinocytosed and transported to the
      multivesicular bodies, suggesting that there may be a precise control of the
      cuticular environment through the turnover of its soluble components.

PMID- 18631485
TI  - Reversible changes in conformation of mitochondria of constant volume.
AB  - When potato mitochondria are prepared in a suitable isotonic or hypertonic
      medium, their morphology depends upon whether or not a macromolecular solute is
      present in the final suspending medium. Any of several chemically disparate
      polymers or macromolecules, above a certain critical concentration, will produce
      filamentous or rod-like mitochondria, which morphologically resemble mitochondria
      in the living cell. Below this critical level, or in the absence of a suitable
      macromolecular solute, mitochondria are spherical, even in hypertonic solution.
      The transition from rod-like to spherical morphology is reversible, rapid and
      independent of metabolism. Swelling of the mitochondria is not involved, since
      there is no change in mitochondrial fresh weight, nor in the optical density of
      mitochondrial suspensions when mitochondria are transformed from one form to the
      other. Alternative mechanisms, based either on screening interaction between
      macromolecules and the mitochondrial membrane, or on the reduction of
      mitochondrial interfacial tension, are proposed to account for the reversible
      changes in morphology. The reversible sphere to rod transition ostensibly depends
      upon the maintenance of mitochondrial resilience or elasticity, which in turn is
      considered to depend upon the presence of an appropriate chelator and sulfhydryl
      agent during the isolation process. In the absence of the latter, mitochondria
      are subsequently irreversibly spherical. Mercaptobenzothiazole effectively
      substitutes for a mixture of EDTA and cysteine.

PMID- 18631486
TI  - Subunits of flagellar accessory tubules.
AB  - Many sperm flagella contain a central pair of singlet tubules surrounded by nine
      doublet tubules. Insect sperm flagella, however, usually contain in addition to
      the typical 9+2 arrangement of tubules, an additional row of nine singlet tubules
      which are called accessory tubules. Each of these accessory tubules in the
      Colorado potato beetle (Leptinotarsa decemlineata (Say)) contains a single
      central prototubule surrounded by an array of 15 or 16 peripheral prototubules.
      The number of prototubules in the accessory tubules of Leptinotarsa decemlineata
      was determined with an electron microscope and image details were reinforced by
      the rotation techniques of Markham.

PMID- 18631487
TI  - Histochemistry and ultrastructure of the mycetome and its 'symbiotes' in the pear
      psylla, Psylla pyricola Foerster (Homoptera).
AB  - The orange-coloured mycetome of the pear psylla, which comprises a cellular
      covering membrane, a number of mycetocytes and a central syncytium, contains two
      kinds of inclusions (micro-organisms-in the literature). As DNA could not be
      detected in them, their status as micro-organisms is questioned. Both kinds
      contain protein; one kind contains RNA, and (by electron microscopy) tubule-like
      peripheral maculae. In spite of their anomalous reactions, the inclusions are
      probably unusual, degenerate or aberrant microorganisms. The biosome theory is
      invoked in explanation.

PMID- 18631488
TI  - Electron microscopy of the rumen ciliate Entodinium caudatum, with special
      reference to the engulfment of bacteria and other particulate matter.
AB  - A study in the electron microscope of thin sections of the rumen ciliate
      Entodinium caudatum was undertaken in an attempt to elucidate the mode of
      engulfment of particulate matter. This protozoon engulfed bacteria, polystyrene
      latex particles and olive oil into membrane-lined vesicles in the protozoal
      endoplasm. Particles of palladium black were also taken up into the endoplasm,
      but due to the toxic nature of this material it was not possible to demonstrate
      vesicle formation with certainty. The initial uptake of bacteria may be into
      large sacs containing many organisms which were subsequently taken into the
      endoplasm in vesicles that contained only one bacterium each. The evidence
      obtained in this investigation has been used to distinguish between two different
      mechanisms for the digestion of bacteria and utilization of the amino acids from
      the bacterial protein for the synthesis of protozoal protein.

PMID- 18631489
TI  - The nature of cnidarian desmocytes.
AB  - The electron microscope reveals that the cnidarian desmocyte is an ectodermal
      cell which forms acidophil protein tonofibrillae intracellularly. One end of the
      cell is bound to mesogleal fibrils; the other becomes embedded in the thickening
      cuticle. The bundle of tonofibrillae later becomes rivet-shaped and the cell
      dies, but still the mesoglea remains bound to the cuticle by means of the rivet.
      The histochemistry and formation of the rivet as well as the comparative cytology
      of cnidarian desmocytes are discussed.

PMID- 18631490
TI  - A follicle cell contribution to the yolk spheres of moth oocytes.
AB  - The incorporation of H(3)-histidine and H(3)-glucosamine by ovarian follicles of
      cecropia moths during incubation in female blood was followed
      autoradicgraphically. Labeling was most prominent in the follicle cells, the
      spaces between these cells, and the nascent yolk spheres in the oocyte cortex.
      Results of pulse-chase experiments and the fact that viable follicle cells were
      required for normal yolk sphere labeling indicated that the endogenous component
      of the yolk was provided by the follicle cells via the intercellular spaces. The
      material was accumulated by the oocyte in the absence of blood proteins,
      suggesting an independent role in yolk formation.

PMID- 18631491
TI  - Lipid droplet and microfilaments in a neuron.
AB  - An isolated example of a neuron containing a large lipid droplet is described.
      The neuron was filled with an unusually large number of microfilaments, which
      were 65 A in diameter and formed a series of plaques surrounding the lipid
      droplet. It is suggested that these 65 A thick microfilaments are formed within
      degenerating neurons and represent a filament different from the 100 A thick
      neurofilament.

PMID- 18631492
TI  - The fine structural localization of acid phosphatase in the prolactin cell of the
      teleost pituitary following the stimulation and inhibition of secretory activity.
AB  - Fine structural studies have been made upon the prolactin cells of Poecilia
      latipinna when the fish is subjected to a series of changes in its environmental
      salinity. Under the regimen employed it is shown that the secretory mechanism of
      the cell is initially stimulated in fresh water and then inhibited in salt water.
      The latter event is accompanied by the appearance of demonstrable acid
      phosphatase activity within the Golgi complex and by the formation of a variety
      of acid phosphatase-positive bodies. The way in which this acid hydrolase
      activity is concerned with the removal of surplus secretory granules is described
      and discussed.

PMID- 18631493
TI  - The fine structure of muscle attachments in a spider (Latrodectus mactans,
      Fabr.).
AB  - The fine structure of a spider myo-apodeme junction is described, and discussed
      in terms of other arthropod muscle attachments. This is contrasted with the
      situation in the venom gland, equipped with muscle fibers that control expulsion
      of the secreted material. The latter involves a cell-free collagenous matrix,
      lying between the muscle cells and the sheath of the gland. As in other
      arthropods, skeletal fibers are attached to the apodeme cuticle via specialized
      epidermal cells, containing oriented microtubules. Interdigitations between these
      cells and muscle, basally, and cuticle, apically, are described. Extracellular
      tonofibrillae described elsewhere are inconspicuous in the apodeme cuticle.

PMID- 18631494
TI  - A two-system model for chitin-protein complexes in insect cuticles.
AB  - Insect cuticles consist of planes of microfibrils which may either form preferred
      oriented layers or rotate progressively to form a helicoid. The two types may
      alternate to form daily growth layers. In Hydrocyrius exo-cuticle, microfibrils
      of diameter 45 A rotate at angles of 7 degrees to 8 degrees to form a helicoid
      with a 44-to 50-fold screw axis, and have an axial periodicity of about 65 A. The
      sense of rotation of helicoidal systems is bilaterally asymmetrical indicating a
      crystallization assembly process, whereas variations in their pitch and
      directions of preferred oriented layers both show bilateral symmetry, indicating
      specific cellular control.

PMID- 18631495
TI  - Neurofilaments and glial filaments.
AB  - The structure of neurofilaments and glial filaments are compared. Both filaments
      are composed of three subunits-a globule, interconnecting crossbar and side-arms.
      These elements form a tubular arrangement and their dimensions are given. Since
      the subunits of both filaments have a similar arrangement but differ in size, it
      is concluded that they represent different proteins.

PMID- 18631496
TI  - Annulate lamellae in an undifferentiated mouse marrow cell.
AB  - Annulate lamellae have been observed in undifferentiated cells in the marrow of
      mice treated with urethan. They were not found in any recognizable hematopoietic
      element in either urethan- or saline-injected controls. The possibility has been
      raised that this cytoplasmic organelle is confined to the most primitive marrow
      cell and may be an identifying feature of 'stem cells'.

PMID- 18631497
TI  - Aspects of fine structure and function of the subcommissural organ of the
      embryonic chick.
AB  - The fine structure of the subcommissural organ (SCO) of the embryonic chick has
      been studied. No evidence of secretory release was obtained. The SCO seems not to
      be involved in such previously suggested roles as water regulation or response to
      varying light cycles. The introduction of electron dense markers into the 3rd
      ventricle demonstrated rapid and massive uptake into coated pits and coated
      vesicles of the ependymal cells and its subsequent incorporation into terminal
      bodies. It is suggested that the uptake of macromolecules from the cerebrospinal
      fluid may be an important and hitherto unsuspected function of the SCO.

PMID- 18631498
TI  - The epithelial origin of lymphocytes in the palatine tonsil of rabbits.
AB  - Lymphopoiesis was studied by electron microscopy in the palatine tonsil of the
      rabbit from 18 days gestation to 5 days after birth. At 18 days tonsils formed as
      mounds of mesenchyma covered with epithelium. At 19 days the basal epithelial
      cells started to increase in number, eventually forming 'buds' which projected
      into the mesenchyme. Simultaneously, lymphocytes appeared nearthe epithelium or
      buds. There was marked resemblance between the basal epithelial cells and the
      lymphocytes. Budding slowed down after the 25th day, but individual basal cells
      continued to migrate into the mesenchyme and lymphocytes increased in number.
      Ultrastructure wassimilar in both types of cells, and differentfrom mesenchymal
      cells. At 29 days lymphocytes were found in the basal epithelial layer behind an
      intact basement membrane. The evidence indicated that lymphocytes were derived
      from epithelium.

PMID- 18631499
TI  - Fine structure of the medullary command nucleus of the electric organ of the
      skate.
AB  - Many axodentritic and axosomatic synapses of chemical type exist in the medullary
      command nucleus which controls the electric organ discharge in the skate (Raia
      clavata and Raia basis). The pre- and postsynaptic membranes are separated from
      each other by a space of about 250 A and they lack regions of tight junction,
      which is thought to form the morphological basis of electrical synapses
      elsewhere. Direct neuronal soma-soma contacts, occasionally encountered in the
      command nucleus, are desmosome-like with no region of tight junction. In contrast
      to conditions observed in many other electric fish, the apparent absence of
      electrical synapses in the skate can be correlated with the asynchronous nature
      of its electric organ discharge.

PMID- 18631500
TI  - Studies on secretory activity in the pars intermedia of Xenopus laevis 1: Fine
      structural changes related to the onset of secretory activity in vivo.
AB  - Changes in the fine structural organization of the pars intermedia related to the
      onset of secretory activity within the gland have been studied. It is shown that
      during the first seven days, following the onset of secretory activity, there is
      an extensive membraneogenesis within the cytoplasm of the parenchymatous cells of
      the pars intermedia which results in the formation of a well-organized array of
      endoplasmic reticulum and an increased development of the Golgi complex.
      Simultaneously the large population of secretory granules present in the cells in
      the inactive condition is reduced, the granules fusing with the plasma membrane
      and releasing their contents into the extracellular space. During the process of
      intracellular reorganization, in addition to the elaboration of those components
      of the Golgi complex which are believed to be concerned with the formation of the
      secretory granules, a second distinctive cisternal element develops within the
      Golgi area. This component which remains confined to the Golgi area for only a
      short time (days 2-4) appears to be responsible for the production of membrane
      bound dense bodies with a finely granular content. The dense bodies, in turn,
      become transformed into the larger heterogeneous structures which are a prominent
      feature of actively secreting pars intermedia cells.

PMID- 18631501
TI  - Studies on secretory activity in the pars intermedia of Xenopus laevis 2: A
      biochemical and electron cytochemical investigation of acid hydrolase activity
      following the stimulation of secretory activity in vivo.
AB  - In the MSH cell at the onset of secretory activity, acid hydrolase activity
      increases. This increased activity, shown quantitatively by assaying beta
      glycerophosphatase and R-glucuronidase within the stimulated gland, has been
      shown by electron cytochemical methods for beta-glycerophosphatase (acid
      phosphatase) and aryl sulphatase to be related to the production of large numbers
      of dense bodies. Cytochemical evidence also supports the view that these lytic
      bodies arise from GERL-like cisternal elements since it is shown that in addition
      to the flattened, parallel Golgi cisternae these elements are also R
      glycerophosphatase-positive. The similarities between the dense bodies and those
      of other cell types are described and discussed.

PMID- 18631502
TI  - Studies on secretory activity in the pars intermedia of Xenopus laevis 3. The
      synthesis and release of melanocyte stimulating hormone (MSH) in vitro.
AB  - Methods of bioassay and electron microscopy have been employed in the study of
      secretion of MSH from single pars intermedia/nervosa lobes maintained in vitro.
      It is shown that in a modified Krebs-Ringer medium the tissue displays an
      endogenous capacity for the synthesis and release of MSH. The amount of MSH
      produced is directly related to the development and functioning of the
      endoplasmic reticulum within the MSH cell, and although a net increase in the
      amount of MSH is adversely affected by anaerobic conditions and low temperature
      it is independent of an exogenous amino acid supply. The release of MSH, which is
      studied both independently and in association with concomitant synthesis, is also
      significantly reduced by anaerobic conditions and low temperature. Of the
      inorganic ions present in the medium only Ca(++) is essential for the synthesis
      and release of MSH. The evidence suggests that more than one step in the
      secretory process is dependent upon an exogenous supply of Ca(++) since in its
      absence the inhibition of MSH release is immediate but reversible, whereas
      although the inhibition of synthesis is delayed it is eventually complete and
      irreversible.

PMID- 18631503
TI  - The organization of a tunicate heart.
AB  - Cardiac myoepithelial cells contain three myofibrils adjacent to the lumen.
      Zonula adhaerentes connect myofibrillar ends; desomosomes and peg-in-socket
      connections occur laterally with zonulae occludenfes at the pericardial border.
      Conduction and contraction are vertebrate cardiac muscle type. T-tubules are
      absent ; atypical sarcoplasmic vesicles run between myofibrils and beneath the
      sarcoplasmic membrane. Multivesiculate vacuoles, on cytoplasmic lobes protruding
      into the lumen from sarcomeric positions, induce reversal of heartbeat by a
      secretory feedback mechanism. Auto-UV-fluorescent dense bodies aooarentlv
      assemble thick and thin filaments. Both pericardial cavity borders are
      pinocytotic. Exaggerated interdigitation of adjacent plasma membranes and thick
      basement membrane of pericardial cells contribute mechanically to heart action.

PMID- 18631504
TI  - The fine structure of developing type 'B' dermal glands in Rhodnius prolixus.
AB  - The fine structure of the developing type 'B' dermal gland, the more common type
      in fifth instar larvae of Rhodnius, is described. Each gland consists of three
      cells responsible for secretion of the duct, saccule and secretion product or
      precursors, and a fourth capsule cell. The cuticular linings of the duct and
      saccule are secreted and shed synchronously with the cuticle of the body surface.
      Mechanisms of secretion and discharge are suggested.

PMID- 18631505
TI  - Moulting in nematodes: The formation of the adult cuticle during the final moult
      of Nippostrongylus brasiliensis.
AB  - The process of moulting and the formation of the new cuticle during the final
      moult of the nematode Nippostrongylus brasiliensis have been described. After
      separation of the hypodermis from the old cuticle, the new cuticle is secreted by
      the hypodermis. The first layers to be formed are the outer trilaminate membrane
      and the fibre layers. The struts of the cuticle separate out from the fibrillar
      and granular components of the outer cuticle. There is no reabsorption of the old
      cuticle.

PMID- 18631506
TI  - Structural lipids in the insect cuticle and the function of the oenocytes.
AB  - Stabilized lipid (cuticulin), combined with protein, serves to stiffen the
      cuticle before sclerotization occurs. It is always present in large amounts in
      exocuticle that will later be tanned to form sclerotin. It is plentiful also in
      the untanned mesocuticle, including the tracheal taenidia, as well as pore
      canals, egg shell and spermatophore sheath. Stabilized lipid present in small
      amounts between the laminae of the endocuticle may perhaps be concerned in
      reversible stiffening and plasticisation. The oenocytes appear to be the source
      of the precursors for cuticulin formation in both larva and reproducing adult.

PMID- 18631507
TI  - The resistance of epicuticular components of an insect to extraction with lipid
      solvents.
AB  - The cuticle of the Calpodes caterpillar has been treated with lipid solvents and
      acids prior to examination in the electron microscope. The 'oriented lipid
      layer', the 'cuticulin layer' and the 'wax canal filaments' are resistant to the
      action of lipid solvents. The 'cuticulin layer' and the 'oriented lipid layer'
      are resistant to acids. Terminology of epicuticular structures is discussed and
      two changes are suggested firstly, to provide a nomenclature that can be applied
      to homologous structures in the cuticles of other insect species and secondly, to
      remove ambiguities arising from the results of this investigation.

PMID- 18631508
TI  - Rapid fixation and embedding for electron microscopy.
AB  - A method has been developed for rapid processing of animal tissues for electron
      microscopy. The whole process of fixation staining dehydration, infiltration and
      embedding including polymerization is completed in less than 4 hr. A variety of
      human and animal tissues such as liver, spleen, muscle, kidney and embryonic
      chick heart were processed by this method and the results were excellent. The
      rapid fixation and embedding method is strongly recommended when relatively soft
      tissues are to be studied. This method is especially useful for examining
      pathological tissues for rapid diagnostic purposes.

PMID- 18631509
TI  - The molt/intermolt cycle in the epidermis and other tissues of an insect Calpodes
      ethlius(Lepidoptera, Hesperiidae).
AB  - Tissue responses to the brain and prothoracic glands divide the 5th larval stage
      of Calpodes into three phases of development, characterized by growth, larval
      syntheses and pupal syntheses. Tissue specific patterns in the timing of nuclear
      events fall into one of two categories. In both, the cell number is determined
      mainly before the 4th to 5th ecdysis. Epidermal cells divide during the second
      phase coincidentally with an elevated rate of larval cuticle deposition, but in
      other tissues nuclear replication occurs without division during the first phase
      so that the cells are polyploid by the time they begin their massive larval
      syntheses.

PMID- 18631510
TI  - The fine structure of the excretory system in adult Nippostrongylus brasiliensis
      (Nematoda) and a suggested function for the 'excretory glands'.
AB  - The ultrastructure of the excretory system, including the subventral glands, of
      the nematode Nippostrongylus brasiliensis has been described. The walls of the
      lateral excretory canals contain canaliculi which open into the lumen of the
      canal. It is suggested that these canals play a role in osmoregulation and
      excretion. The sub-ventral glands contain two types of secretory granule and
      contain non-specific esterase, cholinesterase and aminopeptidase. It is suggested
      that these glands are not excretory but play an important role in feeding.

PMID- 18631511
TI  - The architecture of the accessory reproductive glands of the male desert locust:
      III. Components of the muscular wall.
AB  - An electron microscopic study of the sheath enclosing the accessory reproductive
      glands of the male desert locust has shown that it consists, for the most part,
      of a single myofibril, and that other tissues (nerve fibres, tracheal elements,
      and the fat body) are also associated with it to a greater or lesser extent. The
      myofibril has special features associated with the Z-bands, including the regular
      infolding and the attachment of the sarcolemma at the Z-bands, and the synapsing
      of nerve axons at these infoldings, which perhaps facilitate the rapid
      transmission of nerve impulses into the myofibril. The distribution of the T
      systems and sarcoplasmic reticulum (SR) is described, and their relationship to
      the speed of action of the myofibril is discussed. The myofibril exhibits three
      distinct bands: the A-, I-, and Z-bands. In the A-band, each thick myofilament is
      surrounded by 10 to 12 thin filaments. This finding is related to similar
      findings in other arthropod visceral and slow-acting skeletal muscles. The
      basement membrane surrounding the glandular epithelium comprises two parts: the
      inner part, which is structureless and contains neutral mucopolysaccharide; and
      the outer part which contains numerous collagen-like fibrils and stains for acid
      mucopolysaccharide. This characteristic is considered in relation to the
      insertion and function of the myofibril.

PMID- 18631512
TI  - The growth of new processes from isolated dorsal and sympathetic cell bodies of
      rat and rabbit.
AB  - The ganglia were dissected out from very young and adult rats and rabbits, and
      the cells liberated by teasing. After two weeks incubation at 37 degrees in 199
      medium, 29% to 57% of isolated cells had fine filiform processes. On addition of
      10u/ml of Nerve Growth Factor 10% to 23% more had such processes. Heated control
      cells did not.

PMID- 18631513
TI  - Chromatolysis in a pair of identifiable metathoracic neurons in the cockroach,
      Diploptera punctata.
AB  - The effect of axonal transection upon a specific pair of identifiable nerve cell
      bodies in the metathoracic ganglion of the cockroach, Diploptera punctata, was
      studied by electron microscopy. The response of these cells resembles vertebrate
      chromatolysis in most respects and occurs in two phases : initially, the Golgi
      bodies decrease in size and the Nissl bodies become more concentrated next to the
      nucleus and less concentrated in the periphery of the perikaryon; the morphology
      then changes to one that is more directly concerned with active regeneration of
      the axon. Autoradiographic experiments showed that the initial changes in
      basophilia depend primarily upon movement of the Nissl bodies toward the nucleus
      rather than upon synthesis of new RNA.

PMID- 18631514
TI  - Structural and functional aspects of salivary fluid section in Calliphora.
AB  - Calliphora salivary glands are described, emphasizing correlations between
      structure and physiology. In vitro studies show that the distal part of each
      gland produces a potassium-rich primary saliva when stimulated with 5
      hydroxytryptamine or cyclic AMP. The secretory cells have elaborate canaliculi
      opening into the lumen. Stimulation of the secretory region causes a 60-fold
      increase in fluid secretion rate without affecting cell structure. The proximal
      part of the gland reabsorbs potassium when stimulated with cyclic AMP, but 5-HT
      has no effect. Potassium reabsorption from the primary saliva results in
      formation of a dilute saliva. The structure of the secretory and reabsorptive
      cells is discussed with regard to the functional role of long narrow channels in
      transport.

PMID- 18631515
TI  - Localized deposition of lead phosphate precipitate in glycerinated rabbit psoas
      muscle during ATP-induced contraction.
AB  - The location of ATP-ase sites within sarcomeres was studied by allowing
      glycerinated rabbit psoas muscle to shorten under load in a solution containing
      ATP and lead nitrate. The lead phosphate precipitate formed during the
      contraction is located mainly within the A-band of shortened sarcomeres. In
      fibers glycerinated at rest length, the heaviest precipitate deposits are located
      at the center of the A-band, roughly corresponding to the double overlap zone,
      with lesser precipitate concentrations at the A-l boundary contraction bands. In
      fibers glycerinated at stretched length, shortened sarcomeres with heavy
      contraction bands at the A-l boundary and patent H-bands have heavy precipitate
      deposits over the contraction bands and no localization to the center of the A
      band. The precipitate is thus seen to be most concentrated at those regions where
      one would expect to find the best contact between thick and thin filaments.
      Physiological experiments were performed. Evidence is presented that lead ions
      can substitute for calcium in the contraction process, altering the time course
      of contraction.

PMID- 18631516
TI  - Details of the I band structure as revealed by the localization of ferritin.
AB  - Introduction of ferritin inside muscle fibres deprived of the sarcolemma puts in
      evidence the presence of two lines, here called N lines, which cross the I band.
      In correspondence of the N(1) line, which is nearer to the Z line, the thin
      filaments are disposed in a square pattern. In correspondence of the N(2) line
      the thin filaments are irregularly disposed and glycogen granules occupy the
      spaces between them. Small projections of the thin filaments, which occur at the
      distance of approximately 400 A along the filaments are interpreted as due to the
      presence of tropomyosin.

PMID- 18631517
TI  - The ultrastructural organization of femoral muscles in Musca domestica (Diptera).
AB  - The femoral muscles of Musca domestica are organized as typical synchronous
      muscles. The nuclei occupy the central region of the fibres. The myofibrils have
      a lamellar shape with the major diameter oriented radially with respect to the
      nuclei; they have an extremely regular organization. In cross section each thick
      filament is surrounded by 10-12 thin filaments. The mitochondria are relatively
      abundant and are organized in three concentric layers: perinuclear,
      intermyofibrillar and subsarcolemmal. They have an elongated shape and possess
      numerous cristae, which are oriented trasversally with respect to the long axis
      of mitochondria. The S.R. is organized as a complex system of tubules which
      completely surround the contractile material. The T-system has a characteristic
      shape, and takes contact with the sarcoplasmic reticulum forming peculiar triadic
      structures.

PMID- 18631518
TI  - Disposition of membranes and the entry of haemolymph-borne ferritin in flight
      muscle fibers of the fly Phormia regina.
AB  - The disposition of the surface plasma membrane and its inwardly directed
      derivatives, corresponding to the T-system of other fibers, and of the
      corresponding sarcoplasmic reticulum (SR) elements has been examined in a
      dipteran asynchronous flight muscle (Phormia regina). The presence of uni-axonal
      neuromuscular junctions within clefts approaching the center of the fiber is
      described. The most conspicuous SR component is present in the dyads adjoining
      plasma membrane derivatives, but it is also sparsely represented elsewhere. The
      accessibility of the plasma membrane-limited compartments within the fiber to the
      ambient haemolymph, in the living insect, has been investigated by tracing the
      distribution of ferritin by the circulatory system. The proportion of fiber
      volume occupied by the T-system and SR components in asynchronous and synchronous
      muscle is compared and the functional implications of these proportions is
      discussed.

PMID- 18631519
TI  - The ultrastructure of the sensory plaque organs of the antennae the chinese
      lantern fly, Pyrops Candelaria L., (Homoptera, Fulgoridae).
AB  - The plaque organs of Pyrops consist of elaborately folded, finely perforated
      cuticular areas, each associated with numerous bipolar sensory cells organised in
      groups. The proximal, mitochondrial region of each dendrite narrows to reveal a
      ciliary ultrastructure. The ciliary fibrils pass into a highly vesiculated region
      and beyond this are succeeded by a dense array of neurotubules. Peripherally the
      dendrites proliferate numerous fine branches from which finer filaments extend
      into the cuticular pores. The plaques are considered to be complex olfactory
      organs evolved from groups of sensilla basiconica.

PMID- 18631520
TI  - The injury response of the neurones of Periplaneta Americana.
AB  - Bilateral pairs of specific neurones in the metathoracic ganglion of the
      cockroach were used to study the ultrastructural changes which follow axon
      injury. The appearance of these matched pairs of cells was compared three days
      after the axons on one side of the ganglion only had been severed. The control or
      uninjured cell body appeared normal, but changes were observed in the neurones
      whose axon had been cut. These changes included a general increase in the number
      of ribosomes throughout the cytoplasm, dilatation of the cisternae of the
      endoplasmic reticulum and a reduction in size of the Golgi bodies. No
      ultrastructural features were seen which could correspond to the perinuclear ring
      of RNA observed histochemically with the light microscope. The possible nature of
      this RNA is discussed.

PMID- 18631521
TI  - The fine structure of the procerebrum of pulmonate molluscs, Helix and Limax.
AB  - Neuronal perikarya of the procerebrum of Helix and Limax are generally naked and
      lie side by side. The cell mass contains large numbers of axosomatic and
      axoaxonic synapses represented by boutons of two types; dense core vesicles (800
      1200 A, in diameter) being characteristic of the first type and clusters of
      electron lucent vesicles (500-800 A) of the second. Endings of the two types
      occur also in the terminal mass of the neuropile while the internal mass contains
      peculiar axonal enlargements filled with fine twisted tubuli. Axons containing
      dense core vesicles seem to correspond to varicose monoaminergic fibres detected
      by a fluorescent histochemical method.

PMID- 18631522
TI  - Uptake of peroxidose by the cockroach central nervous system.
AB  - The central nervous system of the cockroach has been incubated with solutions of
      an exogenous tracer substance, horseradish peroxidase, and the sites of its
      penetration and uptake have been studied by electron microscopy. When the nervous
      tissue is intact, or intact but stretched, the peroxidase is taken up throughout
      the neural lamella and also penetrates short distances into the extracellular
      space between adjacent perineurial cells. When the ganglia have been desheathed,
      reaction product for peroxidase is found in the neural lamella, perineurial
      cells, and within the cytoplasmic substance of the glial cells adjacent to the
      desheathed area. This uptake of peroxidase by the injured glial cells in
      desheathed preparations may reflect an alteration in the normal diffusion pathway
      from the external medium to the axonal surfaces.

PMID- 18631523
TI  - The origin of small vesicles in neurosecretory axons.
AB  - The mechanism of release of neurosecretory products from the corpus cardiacum of
      the stick insect Carausius morosus is discussed. Results of experiments using
      ferritin as an exogenous marker show a) direct communication between the cavity
      of the larger (2000 A diameter) vesicles and extracellular space at the axon
      periphery, and b) ferritin also occurs in smaller vesicles (300 A diameter)
      derived, by a process similar to pinocytosis, from the axon surface. These
      findings are discussed in relation to exocytosis and the implications of this
      mode of release in terms of membrane turnover. It is suggested that
      neurosecretory products are released into the haemolymph by fusion between the
      limiting membrane of the neurosecretory droplet and the axon membrane. Small
      vesicles may be involved in retrieval of membrane material, countering that added
      in the above way.

PMID- 18631524
TI  - Septate junctions in the gastrodermal epithelium of Phialidium: A fine structural
      study utilizing ruthenium red.
AB  - The septate junctions of the gastrodermis of the hydromedusa, Phialidium
      gregarium, are composed of septa (80 A thick) which bridge the gap (130 A)
      between the outer leaflets of the plasma membranes of adjacent cells. The septa
      are parallel walls, presumably continuous around the cells, and en face show a
      periodicity of 110 A. Examination of material fixed in a ruthenium red-containing
      mixture shows that this dye penetrates the interseptal compartments and
      illucidates the finer structure of the septa. A model of an interpretation of the
      three-dimensional structure of the junction is presented and relevance of the
      results to current theories of cell communication is discussed.

PMID- 18631525
TI  - Fine structure and histochemistry of the spermathecal gland in the mealworm
      beetle, Tenebrio Molitor.
AB  - The spermathecal accessory gland of female Tenebrio molitor is examined by
      histochemicai and electron microscopical techniques. Immediately after ecdysis of
      the female, neither Golgi regions nor the endoplasmic reticulum of the secretory
      cells are well developed. In two days' time, the cytoplasm is rich in rough
      endoplasmic reticulum and the Golgi areas are expanded. Membrane-bound droplets
      of secretion move from the Golgi zone to a central cavity, formed by the
      invaginated plasma membrane of this cell. As the secretion accumulates this
      cavity swells until the fourth day after ecdysis when the females first mate. An
      efferent cuticular ductule, ensheathed in a ductulecarrying cell, carries the
      product to the main axial duct of the tubular gland. By histochemical criteria,
      the product is a glycoprotein.

PMID- 18631526
TI  - Sclerotization of the perisarc of the calyptoblastic hydroid, Laomedea Flexuosa
      1. The identification and localization of dopamine in the hydroid.
AB  - With histochemical methods, the perisarc and a certain cell type in Laomedea
      flexuosa have been shown to contain a catecholamine. The only catecholamine
      detected in methanolic extracts of the hydroid is dopamine. It is thought to be
      transferred from spherical inclusions in these cells to the perisarc and to be
      involved in sclerotization. The dopamine-containing cells appear to differentiate
      in specific regions of the colony and migrate out to all other regions by active
      amoeboid movement between ectodermal epithelial cells. The rivets (or desmocytes)
      contain an unidentified phenolic substance and may also be sclerotized
      structures.

PMID- 18631527
TI  - The fine structure and deposition of the larval cuticle of the sheep blowfly
      (Lucilia Cuprina).
AB  - The cuticle of Lucilia is composed of an untanned endocuticle and a complex
      epicuticle of four layers, superficial layer, outer epicuticle, cuticulin and
      dense layer. The outer epicuticle and attached epicuticular filaments are
      resistant to acid hydrolysis. During deposition of the cuticle of each larval
      instar, the cuticulin and dense layers are formed first, followed by the outer
      epicuticle, which appears to be laid down by secretions from the epidermis
      passing through the cuticulin via epicuticular filaments. The outer epicuticle is
      found in the position normally occupied by the wax layer of other insect species.

PMID- 18631528
TI  - Fine structure of basal bodies (kinetosomes) and associated components of
      Tetrahymena.
AB  - Basal bodies (kinetosomes) and adjoining structures, notably the rootlets
      (kinetodesmal fibres) and a component of the terminal plate, the rosette, have
      been examined in the electron microscope in sections of whole Tetrahymena and in
      negatively stained fragments from homogenates. The previously described structure
      of the basal bodies has been confirmed and certain details, not apparent in
      sectioned preparations, have been revealed by negative staining. The rosette is a
      filamentous structure with nine-fold symmetry lying between the fibres of the
      basal body at the level of the circumciliary ring. The rootlets are composed in
      the main of a parallel array of filaments with regularly spaced thickenings
      which, being in register, give rise to a transverse banding with a repeat period
      of about 320 A. The rootlets are differentiated at one end for attachment to the
      basal bodies. Some of the structure revealed by negative staining has been
      analysed by means of optical diffraction.

PMID- 18631529
TI  - The fine structure of Methylococcus capsulatus.
AB  - The fine structure of Methylococcus capsulatus is described. Particular emphasis
      is focused on the intracytoplasmic membrane system which is organized as a
      stacked array of flattened saccules. Each saccule is limited by a 75 A unit
      membrane and lies in close apposition to adjacent saccules. Methylococcus
      capsulatus is an obligate methylotroph whose sole source of carbon and energy is
      methane (or methanol). In this study methane oxidation is demonstrated for the
      first time in a cell-free system. Work is in progress to determine the cellular
      organelles which constitute the particulate fraction responsible for methane
      oxidation. The possible role of the intracytoplasmic membranes in energy transfer
      is considered in relation to the functions of stacked membrane arrays in other
      animal, plant and bacterial systems.

PMID- 18631530
TI  - Histochemical specificity of cholinesterases to phenylthioacetate in
      differentiated neural tissues of insects and teleosts.
AB  - Housefly brain cholinesterase was histochemically demonstrated to hydrolyse
      phenylthioacetate at a very high rate, similar in distribution to that previously
      reported for acetylthiocholine. However, teleost neural retina cholinesterase
      would not hydrolyse the aromatic substrate, but the enzyme did cleave
      acetylthiocholine. Paraoxon and eserine were utilized to show selective patterns
      of inhibition in the two tissues. This high degree of substrate selectivity is
      discussed in conjunction with the possible development of selective insecticides.

PMID- 18631531
TI  - Subcellular fractionation of splenic nerve: ATP, chromogranin A and dopamine beta
      hydroxylase in noradrenergic vesicles.
AB  - The subcellular particles in axons of the splenic nerve have been studied by
      centifrugation techniques. By differential centifrugation, five different types
      of particle could be distinguished and partly separated: noradrenaline-containing
      particles (noradrenergic vesicles), large and small lysosomes, mitochondria, and
      microsomal particles. In density gradient centrifugation, only one type of
      noradrenergic vesicle could he demonstrated. The noradrenergic vesicles and the
      mitochondria contain ATP. Two proteins (chromogranin A and dopamine beta
      hydroxylase) are present in the noradrenergic vesicles.

PMID- 18631532
TI  - Release of dopamine beta-hydroxylase and chromogranin A upon stimulation of the
      splenic nerve.
AB  - Two proteins present in noradrenergic vesicles of the splenic nerve (dopamine
      beta-hydroxylase and chromogranin A) are released into the perfusate from the
      spleen when the splenic nerve is stimulated. Experiments in which drugs were
      added to the perfusion fluid showed that the proteins were released from
      terminals of the splenic nerve. There was a correlation between the amounts of
      the proteins released and the quantity of noradrenaline released; and the release
      process was dependent upon calcium. It is suggested that the proteins are
      released from the large dense-cored vesicles present in the terminals of the
      splenic nerve, and that secretion from these vesicles occurs by exocytosis.

PMID- 18631533
TI  - Further investigations on the structure and function of cephalic organs of a
      nemertine Lineus ruber.
AB  - The glandular cells of these paired neuroglandular organs pour their secretions
      (neutral mucopolysaccharide) into a cerebral (cephalic) canal connecting the
      organ lobule to the external medium. The secretions are then taken up by the
      'vesicular cells' lining the blind end of the tube. They are transformed into
      acid -mucopolysaccharide in the vesicular cell and are discharged at the basal
      surface of the cell. The discharged materials are phagocytosed by cells of
      another type which resembles macrophages; these enter the blood lacuna by
      'diapedesis' through the wall of the organ. The activity of the glandular cells
      and vesicular cells changes coincidentally with light and with salt concentration
      in the external medium. The function of the organ is discussed.

PMID- 18631534
TI  - The micromorphology of the nauplius eye of the estuarine calanoid copepod,
      Sulcanus conflictus Nicholls (Crustacea).
AB  - The nauplius eye consists of one median and two lateral ocelli, each within a
      pigment cup. The three pigment cups are made up from two multi-nucleate pigment
      cells: each cell forming one lateral cup and half of the median cup. The three
      cups are lined on the insides by tapetal cells which contain layers of reflectile
      crystals. Each of the ocelli contains six sensory cells which protrude from the
      rims of the pigment cups and the protruding parts are sheathed by the conjunctiva
      cells. The whole eye is enveloped by a thin membrane which also sheaths the
      proximal parts of the five nerve bundles that leave the eye. All the sensory
      cells of the lateral ocelli are similar and have rhabdomeric microvilli on the
      terminal end, and contain phaosomes and a multitude of other organelles and
      cytoplasmic inclusions. The complex median ocellus contains a superior group of
      three retinular cells, linked by interdigitating processes, and an inferior group
      consisting of a large central cell enclosed in two cup-shaped peripheral
      retinular cells. A two-tiered rhabdome arrangement exists, with a rather complex
      inferior rhabdome set made up of a central rhabdomere and two hemi-annulate
      rhabdomeres. The cytoplasm of the retinular cells of the median ocellus lack
      phaosomes but instead contain double-walled tubular elements, possibly formed by
      the inpushings of microvilli into adjacent cells. The possible functional
      significance of the unique arrangement seen in the median ocellus is discussed.
      The retinular cells are of the inverse type. There are no efferent nerve fibres
      from the brain nor any nervous connection between the lateral and the median
      ocelli.

PMID- 18631535
TI  - The fine structure of gill 'podocytes' in Panulirus argus (crustacea).
AB  - A cell type structurally resembling the podocyte of the renal glomerulus is
      situated in the gill of the crustacean Panulirus argus. These cells adjoin the
      medial septum of the gill filament and invariably face the efferent haemolymph
      channel. The basal cell surface is produced into a series of regular ridges,
      between which are inserted elongated cell processes, together constituting a
      palisade that includes narrow slits (250 A or more in width) resembling the
      filtration pores between the foot process of the glomerular epithelium. In each
      instance, the slit is traversed by a diaphragm which in the crustacean 'podocyte'
      is ca. 30 A in width and contiguous with the outer leaflet of the unit membrane
      limiting the cell. Numerous coated vesicles originate from the cell surface
      beneath the diaphragms. The possible role of these cells in detoxification by
      withdrawal of materials from the circulation is discussed.

PMID- 18631536
TI  - The fine structure of the axial organ of the feather star Nemaster rubiginosa
      (echinodermata: crinoidea).
AB  - The fine structure of all the constituent cell type of the crinoid axial organ is
      described (coelomic epithelial cells, muscles, free cells, gland cells and
      neurons) ; also described is the fine structure of the extracellular haemal
      fluid. The gland cells of the glandular tubules of the axial organ have the
      characteristic fine structure of protein exporting cells and may produce granular
      and filamentous components of the haemal fluid. The neurons (perikarya and axons)
      of the axial organ may possibly be neurosecretory, since they are filled with
      electron-dense granules. Homologies between the axial organs of different
      echinoderm classes are discussed.

PMID- 18631537
TI  - Studies on Pogonophora. 4. Fine structure of the cuticle and epidermis.
AB  - The fine structure of the integument in several species of Pogonophora has been
      examined by electron microscopy. The cuticle over the main body is composed of
      several layers of orthogonally arranged fibres embedded in an amorphous matrix.
      It is regularly traversed by microvilli from underlying epidermal cells. Toothed
      bristles of the annuli and setae of the anchor are composed of closely packed
      fibrous cylinders wrapped in a cortical material. In fine structure the cuticle,
      setae, toothed bristles (or setae) and setal sacs forming the setae closely
      resemble the corresponding structures in annelids. The cuticle is maximally thick
      over the forepart (protosome + mesosome) ; it is very thin and non-fibrous over
      the surface of the metameric papillae and over extensive areas of post-metameric
      trunk. The possibilities of a collagenous nature of the cuticle fibres and their
      mode of secretion by the epidermal cells are discussed. The organization of
      various cell-types forming the epidermis over the entire animal is examined.
      Possible functions of these cell-types are discussed. Notable amongst these are
      'possible zymogen cells' and some absorptive cells. The intriguing question of
      nutrition in these gut-less tubiculous animals is re-examined in the light of
      present observations.

PMID- 18631538
TI  - Evidence for changes in nuclear permeability during different physiological
      states.
AB  - It was found that the nuclei of well-fed amoebae accumulate colloidal gold from
      the cytoplasm at a significantly greater rate than the nuclei of cells starved
      for five or nine days. The results are most likely due to a decrease in the
      permeability of the nuclear envelope during starvation. Evidence was obtained
      indicating that the permeability decrease is caused by a change in the functional
      properties of the pores, rather than a change in either pore size or number.
      These findings are consistent with the view that the nuclear pores are involved
      in regulating cellular activity.

PMID- 18631539
TI  - The morphologic and physiologic behaviour of thyroid lobes from newborn rats
      during short periods of incubation in vitro.
AB  - Under light and electron microscopic examination, the morphology of thyroid lobes
      obtained from newborn rats remained essentially normal during periods of
      incubation in vitro lasting as long as several hours. In response to the presence
      of TSH in the incubation medium, follicular cells of the lobes extended long
      microvilli into the follicular lumen and ingested large droplets of colloid. The
      ability of the lobes to carry out essential steps in the synthesis and release of
      thyroid hormone during incubation was demonstrated by radiochromatographic
      analyses. Stimulation with TSH increased the amount of iodide taken up from the
      medium by the lobes.

PMID- 18631540
TI  - Microtubules and the development of the corkscrew region of a mealybug sperm
      bundle.
AB  - Two systems of microtubules appear to be functionally significant in the
      transformation of a small cell into an elongated, acellular 'corkscrew', which
      represents the anterior region of a sperm bundle of Pseudococcus obscurus. One
      system of microtubules lies within the cell; it is oriented parallel to the long
      axis of the cell, and may be important in the elongation of the cell. The other
      system of microtubules is outside of the cell, appears to form a multistranded
      helix around the cell, and may be related to the production of the helical
      contour of the corkscrew.

PMID- 18631541
TI  - Sclerotization of the perisarc of the calyptoblastic hydroid, Laomedea flexuosa
      2. Histochemical demonstration of phenol oxidase and attempted demonstration of
      peroxidase.
AB  - Histoehemical evidence is presented that cells, described as 'tanning cells', in
      the hydroid Laomedea flexuosa contain an orthodihydroxyphenol oxidase and
      transfer this enzyme to the perisarc. The detection of copper in the tanning
      cells provides further evidence for the presence of phenol oxidase, a copper
      containing enzyme. Evidence is presented that this enzyme and the
      orthodihydroxyphenol, dopamine, are stored together in the same 1mu diameter
      spherical inclusions. The enzyme and orthodihydroxyphenolic substrate appear to
      be transferred together to the perisarc where it is thought that the dopamine is
      oxidized by the phenol oxidase to produce a quinone. The quinone is thought to
      cross-link the structural proteins to form a strong, inert exoskeleton, the
      perisarc. Attempts to demonstrate peroxidase using benzidine methods are also
      described. Both the spherical inclusions of the tanning cells and the perisarc of
      the hydrothecae give a reaction with benzidine in the absence of hydrogen
      peroxide. This suggests the presence of an oxidizing agent which is not a
      peroxidase but is possibly a quinone.

PMID- 18631542
TI  - Chaetopterus tubes: Ultrastructural architecture.
AB  - The wall of the tube 'house' constructed by the polychaetc, Chaelopterus
      variopedatus, was examined by scanning and transmission electron microscopy and
      polarizing and phase-contrast light microscopy. The tube wall consists of
      alternating plies of aligned protein fibres imbedded in an unstructured matrix.
      The protein fibres range in diameter from 50-400 mmu and have an axial
      periodicity of about 641 A. The relative proportion of fibres to matrix, the
      total number of plies, and the number of fibres per ply vary throughout the tube.

PMID- 18631543
TI  - The stridulatory apparatus of two species of Tettigoniid.
AB  - A scanning electron microscopical examination has been made of the stridulatory
      apparatus of Homorocoryphus nitidulus vicinus (Wlk.) and Jamaiciana flava (Wlk.).
      Its structure is discussed in relation to function, and the probable affinities
      of the two species within the Tettigoniidae.

PMID- 18631544
TI  - Ultrastructure of the copper-accumulating region of the Drosophila larval midgut.
AB  - The copper-accumulating region of the midgut is a mosaic of interstitial and cup
      shaped, copper-accumulating cells. The cup of each cuprophilic cell is lined with
      a highly refractile border of long microvilli except in one strain where it is
      predominantly lamellar. The nucleus lies basally; the basal plasma membrane is
      fairly extensively infolded. Cytolysomes are abundant and increase in number with
      increasing copper content of the diet. The interstitial cells bear short, less
      regular microvilli and have a less electron-dense cytoplasm. The nucleus is
      apical, the mitochondria-associated basal membrane is very extensively infolded
      and cytolysomes are less abundant. Virus-like particles present in nuclei of both
      cell types increase in number with increasing copper concentration.

PMID- 18631545
TI  - The distribution of phenoloxidases and polyphenols during cuticle formation.
AB  - The distribution of phenoloxidase and polyphenols have been studied during
      cuticle formation at the 4th to 5th molt in Colpodes ethius. Cuticular
      phenoloxidases arise in the epidermis in cisternae of the rough endoplasmic
      reticulum, pass through the Golgi complex and are transported to the apical face
      in secretory vesicles. From the cuticular environment some enzyme is pinocytosed
      and broken down in the apical multivesicular bodies. Phenoloxidase and
      polyphenols are present during the formation of the cuticulin layer which also
      reacts as if it were at least partly composed of a phenoloxidase. The rest of the
      epicuticle incorporates phenoloxidase as it is deposited, particularly that over
      the dorsal tubercles which later melanize. Polyphenols do not appear until
      shortly before ecdysis. They are associated with the epicuticular filaments in
      both epicuticle and presumptive epocuticle. It is proposed that the epicuticular
      filaments may arise as liquid crystals with a protein component which becomes
      stabilized like the rest of the cuticle. These structures could provide a channel
      for the movement of both lipids and quinones to the surface. Phenoloxidases may
      pass through fibrous cuticle to be deposited as part of the epicuticle but are
      incorporated in fibrous cuticle scheduled for sclerotization. The time of
      stabilization is determined by the availability of polyphenols.

PMID- 18631546
TI  - Metamorphosis of midgut epithelial cells in the silkworm (Bombyx Mori L.) with
      special regard to the calcium salt deposits in the cytoplasm. I. light
      microscopy.
AB  - The morphological changes of the metamorphosing midgut cell in the silkworm were
      traced light-microscopically. The regenerative cells of the larval midgut
      proliferate rapidly during larval-pupal molt and finally replace the larval
      midgut, establishing new pupal midgut tissue composed of only one cell type.
      Pupal midgut cells contain numerous basophilic granules which are believed on
      histological grounds to be the deposits of calcium salts. Calcium seems to be
      transported from hemolymph to the pupal midgut cells and stored there temporarily
      as insoluble salts such as phosphate or carbonate, and then finally discharged
      into the lumen in a merocrine fashion. The midgut cells of the adult no longer
      contain calcium deposits.

PMID- 18631547
TI  - Electron microscopy of stomatogastric ganglion in the lobster Homarus americanus.
AB  - The stomatogastric ganglion and two of the associated afferent and efferent nerve
      trunks (stomatogastric and dorsal ventricular nerves) from Homarus americanus
      have been examined with light and electron microscopy after glutaraldehyde-osmium
      tetroxide fixation. The dorsally located neuron somata, rich in ribosomes and
      glycogen, are encased in multi-layered glial and fibrous sheaths. The synaptic
      neuropil regions occur scattered throughout the central and ventral part of the
      ganglion, interspersed amonglarger nerve fibres of extrinsic and intrinsic origin
      from which the neuropil is derived. Neural processes containing masses of small
      clear vesicles plus larger dense-core vesicles make apparent synaptic contacts at
      points of increased membrane density with smaller, non-vesicle-containing or
      sometimes other vesicle-containing nerve fibres.

PMID- 18631548
TI  - The fine structure of the ovary of the feather star Nemaster rubiginosa
      (Echinodermata: Crinoidea).
AB  - The outer layer of the crinoid ovary consists of coelomic epithelium, smooth
      muscles, and nerve cell processes. The middle layer of the ovary contains non
      germinal accessory cells, small germinal cells (either oogonia or pre-leptotene
      primary oocytes), and post-pachytene primary oocytes; all these cells are
      completely embedded in a haemal matrix of 200 A-diameter granules. The primary
      oocytes larger than 20mu in diameter have abundant invaginations in the plasma
      membrane, suggesting uptake of materials from the haemal matrix. The innermost
      layer of the ovary is a ciliated epithelium lining the cell-free ovarian lumen.

PMID- 18631549
TI  - The relationship between complex vesicles, dense-cored vesicles and dense
      projections in cortical synaptosomes.
AB  - Cortical synaptosomes fixed in unbuffered OsO4 and glutaraldehyde have been block
      stained with phosphotungstic acid (PTA) in order to investigate the relationship
      between complex vesicles and dense projections. It is concluded that the shell of
      the complex vesicles contributes to the formation of dense projections and that,
      in addition, there is a correspondence between this shell and the previously
      described presynaptic network. The process by which complex vesicles become
      associated with dense projections appears to be accentuated by electrical
      stimulation of the synaptosomes.

PMID- 18631550
TI  - Electrophysiological and structural studies on the heart muscle of the lobster
      Homarus americanus.
AB  - The electrophysiological properties and structure of heart muscle fibres of the
      lobster myocardium have been investigated. Discontinuities were observed in the
      expected decrement of electrotonic potentials in a study of the passive membrane
      properties of the muscle. Injection of Procion yellow revealed transverse
      barriers to dye movement, identified in electron micrographs as intercellular
      junctions. Unlike the intercalated discs of the vertebrate myocardium, which
      these regions superficially resemble, nexus regions of 'close' or 'gap' junctions
      are absent. The intercellular cleft is generally 400 A in width, locally reduced
      to 75-100 A The functional implications of these findings are discussed. Cardiac
      myoneural junctions, which include regularly repeating structures extending into
      the synaptic cleft from the postsynaptic membrane, are described.

PMID- 18631551
TI  - Extracellular crystalline material in intercellular spaces of cockroach
      peripheral glia.
AB  - Campaniform sensilla on legs of the cockroach, Blaberus discoidalis, are
      mechanoreceptors; each sensillum functions via a single bipolar neuron. The cell
      bodies of the bipolar neurons are tunicated; that is, they are spirally wrapped
      by one or more glial cells. An elaborate extracellular channel is defined by the
      plasma membranes of adjacent glial cell folds surrounding a given neuron. The
      electron microscope reveals that this extracellular space often contains
      conspicuous crystalline material whose lattice planes, oriented at right angles
      to the long crystal axis, are manifest as parallel electron-dense lines separated
      by an intercentre distance of 150 A. The chemical nature of these crystals has
      not been determined in the present study. Like most biological crystals, however,
      this precisely ordered crystalline material is probably proteinaceous.

PMID- 18631552
TI  - Microscopic localization of cholinesterases in the nervous systems of the
      lobsters, Panulirus argus and Homarus americanus.
AB  - Using acetylthiocholine as substrate, microscopically localizable cholinesterase
      (ChE) activity is demonstrated in neural and glial elements of central and
      peripheral nervous systems of the lobsters, Panulirus argus and Homarus
      americanus. Moderate to very intense ChE activity occurs in all synaptic regions
      of the central ganglia and stomatogastric ganglion, in glial sheaths around
      neuron somata and peripheral nerve axons, and in cytoplasm of a few nerve cell
      bodies. Axons, identified as motor, contain extremely little ChE. The principal
      reaction in peripheral nerves occurs in sheath elements of sensory fibres; in
      most cases, much of the reaction is lost as the nerves lose the sheaths at the
      point of entry into brain.

PMID- 18631553
TI  - Vinblastine-induced disruption of microtubules in cockroach hemocytes.
AB  - Intrahemocoelic injections of vinblastine (10(-3), 10(-4)M) resulted in the
      disappearance of microtubule marginal bundles in the hemocytes of Periplaneta
      americana L. concomitant with a change in lenticular cell shape as determined by
      electron microscopy. In contrast to control cells, which in section were
      elliptical in shape with smooth edges, treated cells displayed large vacuoles
      apparently resulting from folds in the cytoplasm and an irregular shape.
      Vinblastine concentrations lethal to insects (25micro1/insect, 10(-3)M) resulted
      in marginal bundle loss, and the formation of cytoplasmic linear material with
      associated ribosomes, although microtubule crystals were not found.

PMID- 18631554
TI  - Membrane systems of freeze-etched striated muscle.
AB  - The organization of flight muscle of a dragonfly, with special reference to the
      fibre membrane systems, has been investigated by means of platinum-carbon
      replicas of freeze-etched material. The fractured surface plasma membrane and
      origin of transverse tubules are described together with the radial course of the
      tubules into the cell, along grooves in the mitochondrial surface. The form of
      the sarcoplasmic reticulum cisternae is also described. Replicas are interpreted
      as revealing up to three unfractured membrane surfaces and several fractured
      profiles. The illustrations include stereo-micrographs of replicas.

PMID- 18631555
TI  - The fine structure of the developmental stages of the microsporidian Nosema apis
      Zander.
AB  - Schizonts, sporonts and sporoblasts of Nosema apis from honey bees collected in
      the summer and winter were studied with the electron microscope. The nuclei
      usually had a diplokaryon arrangement. Intranuclear spindles with polar vesicles
      were associated with division. Schizonts had a single limiting unit membrane,
      whereas sporonts had a two-layered wall. Sporonts from summer bees had only a
      thin single limiting membrane in some areas and evidence of endocytosis was
      sometimes seen in these. Sporonts from winter bees had branched tubular
      outpocketings from the wall. In sporoblasts, the development of the polar
      filament was closely associated with a network of dense structures interwoven
      with a system of tubules evidently of ER derivation; the Golgi complex was
      associated with this network.

PMID- 18631556
TI  - Fine structure of the prothoracic mycangium, a chamber for the culture of
      symbiotic fungi, in the southern pine beetle, Dendroctonus frontalis.
AB  - The ultrastructure of the prothoracic mycangium of female Dendroctonus frontalis
      is examined. The mycangium consists of a cuticular invagination within which
      symbiotic fungi are cultured by the pine beetle and transported to new host
      trees. Secretions from two types of gland cells pass into the mycangial lumen.
      The plasma membrane of type-1 cells is invaginated to form an enclosed
      extracellular cavity. The secretory product passes into the cavity, then through
      fine cylindrical channels into an end apparatus and finally via an efferent
      cuticular ductule to the lumen of the mycangium. Secretion of the type-2 cells is
      released into a cavity just beneath the mycangial cuticle. The cuticle over this
      cavity is quite thin (1-2micro), consisting mostly of inner epicuticle riddled
      with irregular canals through which the secretion reaches the lumen. Beneath the
      patches of porous cuticle are ribs (up to 10micro in thickness) which flank the
      cavities and presumably provide structural support for the porous secretory
      zones.

PMID- 18631557
TI  - The architecture of the accessory reproductive glands of the male desert locust.
      5: ultrastructure during maturation.
AB  - The accessory reproductive glands of the male desert locust were studied with the
      electron microscope from the time of adult emergence until full sexual maturity
      was attained (10 days). Observations on the changes in the nucleus and the
      cytoplasm of the glandular epithelium, particularly those organelles involved in
      the elaboration of cell secretions, were made during the maturation of the
      accessory glands. Cells of gland 16 (the functional seminal vesicle) exhibit
      numerous ribosomal aggregates, have a concentration of mitochondria along their
      luminal surface, and show some secretory activity, even at the time of adult
      emergence. On the other hand, all other accessory glands show very little
      development of the secretory apparatus (rough-surfaced endoplasmic reticulum,
      polyribosomes, Golgi elements, elaborate mitochondria, etc.) until after the
      fifth adult day. These changes parallel changes in the secretory activity of the
      adult corpus allatum; and it is suggested that the corpus allatum hormone
      regulates the maturation of the truly glandular accessory glands of the locust,
      but not that of the functional vesicle.

PMID- 18631558
TI  - A study in the light and electron microscope of the extruded peristome and
      related structures of the rumen ciliate entodinium caudatum.
AB  - A study in the light and electron microscope of sections of the rumen ciliate
      Entodinium caudatum was undertaken in an attempt to elucidate the structure of
      the peristome when in the extruded state The conformation of the ciliary band on
      the peristome and the structure of the lining of the buccal cavity are described.
      The structure and position of a tuft of specialized sheet like extensions of the
      cell surface is also described.

PMID- 18631559
TI  - Studies in the electron microscope of the adoral zone of membranelles of the
      rumen ciliate entodinium caudatum using the technique of negative staining.
AB  - The structure of the organelles situated beneath the kinetosomes in the adoral
      zone of membranelles of the rumen ciliate Entodinium caudatum have been
      investigated in the electron microscope using the technique of negative staining.
      Each kinetosome was joined to a sub-kinetosomal plate and these plates were
      joined together in rows which in turn were more loosely linked to form a sheet.
      The structure or these plates is described and their relationship to similar
      structures in other protozoa is discussed. The nature of the argentophilic
      structures observed in the light microscope at the anterior end of Entodinium
      caudatum has also been investigated in the electron microscope.

PMID- 18631560
TI  - Histochemical localization of biogenic monoamines in the posterior salivary
      glands of octopods.
AB  - Tubules of the octopod posterior salivary gland are lined by two distinct
      epithelia, type A and B of which type A is predominant. A positive chromaffin
      reaction is given only by a small proportion of columnar cells of the type A
      epithelium, and is apparently associated with the large (3mu) cytoplasmic
      granules of these cells. A similar proportion of type A columnar cells exhibit
      formaldehyde-specific fluorescence which is not reduced by reserpine in doses
      which reduced fluorescence in the optic lobes and in fibres associated with
      myoendothelial cells investing the posterior salivary gland tubules.

PMID- 18631561
TI  - Microtubules and filaments in developing axons and optic stalk cells.
AB  - Fibrous structures have been studied in the developing optic nerve of chick
      embryos. The first ganglion cell axons (3-day embryos) were of moderate size,
      with both neurofilaments and microtubules. Subsequently (4- and 5-day embryos),
      very small axons were also present. In thesc embryos and in the 4-day hatched
      chick, the density of microtubules fell within the same range for all but the
      very small axons, which tended to have more microtubules per unit area. Filaments
      similar to those previously thought to represent neurofilaments in other parts of
      the embryonic nervous system were present in the early optic stalk cells, calling
      into question the reliability of identifying early nerve cells on the basis of
      'neurofilaments'.

PMID- 18631562
TI  - Annulate lamellae in hamster pineal gland.
AB  - Pineal glands from young adult hamsters (Mesocricetus auratus Water-house) kept
      on a 14-10 light-dark photoperiod contain annulate lamellae. These annulate
      lamellae are apparently limited to the light pinealocytes. They are found in
      close proximity to nuclei, the Golgi apparatus, and agranular endoplasmic
      reticulum. There is also an interesting association or microtubules with the
      annulate lamellae. It seems reasonable that the presence of annulate lainellae in
      the pinealocytes may have some correlation with the physiological function or
      functions of these cells.

PMID- 18631563
TI  - The fine structure of cockroach blood cells.
AB  - Electron-mictoscopic observations of the blood cells (Haemocytes) in the legs of
      the cockroach Blaberus discoidalis reveal three 'types' of cells distinguishable
      on the basis of fine structure. One type of cell contains numerous membrane
      limited opaque bodies which may be lysosomes. A second type contains abundant
      digestive vacuoles and appears phagocytic. A third type, frequently encountered
      in rewlymoulted untanned animals but less often observed in mature adults,
      contains membrane-limited tubule-containing bodies (TCB) filled with rows of 340
      A tubules which are quite different from cytoplasmic microtubules. It is
      suggested that haemocytes containing TCB may be equivalent to the coagulocytes
      (cystocytes) of light microscopy which actively participate-in-the process of
      haemolymph coagulation in Orthoptera. No attempt whatsoever is made at
      classification. Since considerable overlap in fine structure exists between cell
      types, it seems probable that the electron-images of fixed cells observed in this
      study represent several morphological expressions of which an individual cell may
      be capable during its lifetime.

PMID- 18631564
TI  - Some morphological aspects of the innervation of a spider's silk gland.
AB  - A structure in the ampullate silk gland of an orb-weaving spider, previously
      thought to be a pressure receptor, was studied by electron microscopy to clarify
      its sensory function. This lamellated 'bulbous region' is situated between the
      gland and the beginning duct, which consists of a layered, acellular matrix (muco
      protein), surrounded by a flat epithelium and partly covered by connective
      tissue. The epithelial cells are densely filled by a mesh-work of microtubules
      and interconnected by extensive cell junctions, both indicating exposure to
      mechanical stress. The few nerve fibres found to supply the bulbous region do not
      exhibit specialized dendritic endings and provide no evidence for a receptor
      function. The abundance of translucent vesicles of 400-500 A (synaptic'?) and
      dense granules of 1000-1500 A (neurosecretory?) indicate efferent fibres,
      possibly controlling the secretion of the matrix. The function of the bulbous
      region remains to be investigated. Similar nerve fibres but with distinct
      synaptic foci were noted in the adjacent gland duct in large numbers. The neuro
      glandular synapses have a characteristic location, namely, opposing the mesaxon
      like invagination of the epidermal cells. These nerve fibres are believed to play
      a role in water uptake and/or secretion of the extra-cellular duct lining.

PMID- 18631565
TI  - Structure and distribution of fibre types in the external eye muscles of the rat.
AB  - Rat extraocular muscles are composed of two layers differing in muscle fibre
      diameter. In both layers multiply innervated fibres are found besides focally
      innervated ones. Significant differences in internal structure thus demand
      further subtyping. The global layer (predominantly larger fibres) contains 10"
      'clear' fibres (multiple innervation, medium size) and a spectrum of focally
      innervated fibres, from small 'dark' fibres (30%, abundant mitochondria) over
      'intermediate' fibres (30%) to large 'pale' fibres (30 %, few mitochondria). The
      orbital layer (exclusively small fibres) contains 80% focally innervated 'dark'
      fibres and 20% extremely small 'clear' fibres with multiple innervation. An
      ultrastructural characterization of the fibre types is given and possible
      functional implications are discussed.

PMID- 18631566
TI  - The ommatidium of the termite mastotermes darwiniensis.
AB  - An electron microscope study of the compound eye of the termite Mastotermes
      darwiniensis shows that the ommatidia have both primitive and specialized
      features. The ommatidia are of the apposition type with eight similar retinular
      cells, a fused rhabdom, irregularly orientated rhabdomere tubules and no
      tracheae. The retinula cells contain lipid. The cone cells have unusual
      processes, which thicken towards the basement membrane and contain rough
      endoplasmic reticulum, granules and dense bodies. These processes may act as a
      primitive transport system for nutrients.

PMID- 18631567
TI  - Fine structure of the chorion of a moth, hyalophora cecropia.
AB  - The chorion of the moth Hyalophora cecropia has been found to consist primarily
      of a complex of proteins rendered insoluble by disulfide and hydrogen bonds. The
      bulk of the chorion is lamellate, and as in many cuticles each lamella contains a
      regular helicoidal series of microfibrils. The lamellar organization is disrupted
      in a central zone containing narrow irregular channels, and elsewhere the mature
      chorion is traversed by wide cylindrical channels. These open to the outer
      chorion surface indirectly via a porous trabeculate zone, and are distinct from
      the channels leading to the aeropyles, described elsewhere, in lacking
      cytoplasmic processes during their formation.

PMID- 18631568
TI  - La formation des canaux cuticulaires chez l'adulte de Tenebrio molitor L. etude
      ultrastructurale et remarques histochimiques.
AB  - The sclerotized cuticle of adult Tenebrio shows (1) an exocuticle composed of
      rotating lamellate layers and of columns of cuticular material, the fibres of
      which run perpendicularly through the lamellae, (2) an endocuticle composed of
      layers with preferred orientation. In the exocuticle, the pore canals are
      numerous and run along the columns; they do not rotate with the lamellate layers.
      They show several filaments some of which leave the canals and form a dense
      intracuticular network. In the last layers of exocuticle, the pericolumnar canals
      fuse and form large endocuticular canals which rotate in phase with the cuticular
      fibres. The formation of columns and canals is in relation with cellular
      expansions which penetrate into the cuticle during cuticle deposition.
      Exocuticular columns seem characteristic of highly sclerotized cuticles and the
      intracuticular filaments may have a role in the transport of sclerotisation
      precursors.

PMID- 18631569
TI  - The arrangement of chromatin in the interphase nucleus with reference to cell
      differentiation and repression in higher organisms.
AB  - HeLa cells were grown as monolayer cultures in Spinner medium and given 12-minute
      pulse labels of (3)H thymidine. Synchronous crops of cells labelled in the last
      minutes of S showed a metaphase pattern of chromosomes hot-labelled close to the
      kinetochores (centromeres). Such cells in subsequent stages of interphase showed
      a concentration of label at the nuclear envelope. A control experiment with cells
      labelled in the first minutes of S yielded chromosomes labelled at the tips and
      in the nucleolar organizers. These cells showed label concentrated in the central
      area of the nucleus in the next interphase. The results are compatible with the
      view that the kinetochore regions of chromosomes are attached to the nuclear
      envelope in interphase. The significance of these results is considered with
      reference to interpreting DNA replication patterns, the segregation of
      chromosomes, eukaryote differentiation and repression, and the rationale for
      chromosome numbers. It is argued that the nuclear envelope serves as a 'repressor
      organelle' in higher organisms, and that DNA methylation may be involved in the
      control of RNA transcription, and hence gene expression.

PMID- 18631570
TI  - Scanning electron microscopy of the spermatheca in Sitophilus granarius (L.).
AB  - With scanning electron microscopy the spermathecal organ of Sitophilus granarius
      (L.) has been examined. The only morphological attachment between this organ and
      other tissues is to the bursa copulatrix by the sperm duct and to the central
      nervous system by two nerve fibers. The nerves innervate the muscles connecting
      the two arms of the U-shaped spermatheca. Glandular cells are grouped together
      and are connected to the spermathecal lumen by a short collecting duct. Vascular
      sinuses opening from the body cavity into the body of the gland are observed as
      pores on the surface of the gland.

PMID- 18631571
TI  - Prolactin-induced stimulation of H(3)-proline incorporation into the basement
      lamella of tadpole skin: light and electron microscope study.
AB  - Radioautographic studies revealed that prolactin markedly stimulates the
      incorporation of H(3)-proline into the basement lamella of the tail fin of frog
      tadpole. Radioactivity in fibroblasts reached a peak at 3 hours. Thereafter, the
      number of silver grains in fibroblasts was reduced with concomitant increase in
      the basement lamella. Fibroblasts of the prolactin animals also showed
      extensively developed rough endoplasmic reticulum and Golgi elements. Epidermis
      of control animals was labelled as in the prolactin animals, although the
      basement lamella was sparsely labelled. Fibroblasts, not the epidermis, seem to
      secrete collagen into the basement lamella.

PMID- 18631572
TI  - Fine structure of clear cells in frog epidermis.
AB  - The fine structure of clear cells located within the frog epidermis was
      investigated. Characteristic features of clear cells were, the 'flask-like'
      shape, the sparse amount of filaments resulting in a clear cytoplasmic
      appearance, abundant mitochondria, numerous small vesicles, and a system of
      convoluted apical membranes in cells adjacent to horny cells. These features were
      suggestive of a secretory function for the clear cell. A comparison of clear
      cells with fully differentiated epidermal cells (functioning in protection) was
      made, in an attempt to discover how structural differences between the two cells
      were related to the basic functions of the cells.

PMID- 18631573
TI  - Fine structure, functional organization and supportive role of neuroglia in
      Nereis.
AB  - Fluorescence and electron microscopy reveal a dynamic architectural pattern in
      the organization of neuroglia in the central nervous system of nereid
      polychaetes. Fibrous glial processes intertwine among neuronal elements, binding
      them together, and anchor the nerve cord to the epidermis. Rigidity and
      resilience are provided to this supportive framework by glial filaments and
      desmosomes. Tensive stresses, arising from contraction of locomotory muscles
      attached to the nerve cord, may be dissipated over the web-like meshwork, thus
      reducing the potential influence of deformative forces on neuronal elements
      within the neuropile. The voluminous glial processes forming the peripheral zone
      of the nerve cord may protect neurons from compressive forces.

PMID- 18631574
TI  - The distribution of the neural fat body sheath and the accessibility of the
      extraneural space in the stick insect, Carausius morosus.
AB  - The fluid compartment delimited at the surface of the central nervous system by
      the closely applied fat body sheath has been shown to be accessible to molecules
      of horseradish peroxidase and Indian ink particles. Quantitative analysis
      indicates that leakage via the intercellular spaces between fat body cells would
      preclude the possibility of a significant involvement of the fat body cells in
      sodium regulation of the extraneural fluid. This possibility is further precluded
      by the absence of a fat body sheath from peripheral nerves.

PMID- 18631575
TI  - The fine structure of muscle attachments in an acarid mite, Caloglyphus
      mycophagus (Megnin) (Acarina).
AB  - The fine structure of the myo-cuticular junction in an acarid mite, Caloglyphus
      mycophagus, is described. The muscle fibres are attached to the cuticle via
      flattened, much invaginated, epidermal cells. Unlike the situation described for
      other arthropods, the stress across these epidermal cells does not appear to be
      transmitted by microtubules but rather by desmosome-like structures which form
      intraepidermal cell bridges where invaginations from the outer and inner surfaces
      of the epidermal cells lie close together. The muscles are attached to the inner
      surface of this complex desmosome and the outer surface is linked to the cuticle
      by extracellular fibrils.

PMID- 18631576
TI  - Ovarian intercellular bridges in Dermacentor andersoni stiles (Acari : Ixodidae).
AB  - Intercellular bridges are present between oogonia and between oocytes of nymphs
      and newly molted and fasting adult Dermacentor andersoni Stiles. During these
      stages there is synchronous development of oogonia and oocytes. These bridges are
      unique both in their degree of development and in possessing narrow, elongated
      invaginations of the plasma membrane around both bases. Dictyosomes are
      frequently present in close proximity to bridge bases and vesicles are often
      noted in bridges between oocytes of adults. Bridges between oogonia infrequently
      contain cisternae of smooth endoplasmic reticulum.

PMID- 18631577
TI  - The fine structure of ciliated sensory cells in the epidermis of the earthworm
      Lumbricus terrestris.
AB  - An ultrastructural study of the earthworm body wall has revealed three types of
      sensory cells. Two, the multiciliate and uniciliate sensory cells, are found only
      in the discrete sense organs and their cilia pass vertically through the cuticle.
      The third type-isolated multiciliate sensory cells-are scattered throughout the
      epidermis and never grouped together. However, their cilia do not pass through
      the cuticle, but run horizontally over the outer surface of the epidermal cells.
      The structure of the sensory cells is described and compared with that of
      ordinary epidermal cells and the supporting cells found in the sense organs.
      Their possible physiological roles are discussed.

PMID- 18631578
TI  - A possible sensory-motor neuron in Aplysia californica.
AB  - A granule-containing cell is described in the secretory epithelia of the
      accessory genital mass in Aplysia californica. The ciliated apical process of
      this cell protrudes into the lumen of the oviduct. The granule-containing basal
      region of the cell is drawn out into fine processes that resemble axons. Granule
      filled dilatations of these axons are found directly under large secretory cells.
      On this basis, it is suggested that these cells fulfill the morphological
      criteria for sensory-motor cells, and this data will be used as a basis for
      microelectrode studies to confirm or deny the above suggestion.

PMID- 18631579
TI  - Antennal chemoreceptors of the desert burrowing cockroach, Arenivaga sp.
AB  - The antennae of Arenivaga have six types of chemoreceptor sensilla. Some of these
      have unusual morphological features which may be adaptations for survival in a
      dry habitat. The sensory dendrites are well protected by cuticular structures,
      and in some receptors stimulatory molecules must pass through long channels or
      through pores filled with strands to reach the sensory cells. Large grooved pegs
      (possibly pheromone receptors) are numerous on antennae of adult males, and
      grooved sensilla are described here in detail for the first time. Thin-walled
      pegs, present in males and females, do not have pore tubules or hollow filaments
      as observed in many other insects. Rather, they contain structures designated
      here as pore strands, since they have a dense core rather than a light center as
      previously described for pore tubules and filaments. These strands do not appear
      to be evaginations of the dendritic membrane, but are probably formed in
      association with the cuticular structures of the sensilla.

PMID- 18631580
TI  - The role of pore structures in the selective permeability of antennal sensilla of
      the desert burrowing cockroach, Arenivaga sp.
AB  - To obtain information about the chemical composition of pore structures in
      antennal sensilla, the antennae were exposed to lipid solvents, or they were
      prepared to show negative-contrast images in electron micrographs. A heavy-metal
      tracer, lanthanum nitrate, was also used to indicate the permeability of the
      receptors to water. The grooves of the large grooved peg open into tubular
      cavities containing electron-opaque material, through which stimulatory molecules
      must pass to reach the sensory dendrites at the center of the sensillum. The
      material in these cavities was removed by chloroform or acetone, suggesting a
      lipid composition. Lanthanum penetrated this receptor only after it had been
      exposed to acetone or chloroform. Strands at pores of the thin-walled pegs were
      also removed by the lipid solvents, and the water-soluble tracer failed to
      penetrate these receptors unless they had been previously exposed to chloroform
      or acetone. The pore structures appear to be hydrophobic, allowing entry of lipid
      soluble substances, while preventing passage of water. The differential action of
      the solvents on the various types of sensilla suggests that receptor
      discrimination among different classes of chemical stimuli may be partially
      determined by the chemical properties of structures at the sensillar pores.

PMID- 18631581
TI  - The fine structure of the neurons in the rat substantia nigra.
AB  - Three distinct neurons were identified in the substantia nigra of the rat using
      Golgi, light, and electron microscopic techniques. A large neuron, found in the
      pars reticulata, is characterized by well-developed RER, a tubular cytoplasmic
      inclusion, and somatic and dendritic thorns. A medium-sized neuron, found in the
      pars compacta, has an eccentric nucleus, distinct Nissl bodies, and an inclusion
      composed of whorls of concentric cisternae. A small neuron, found in both nigral
      regions, contains a highly invaginated nucleus, fibrous nuclear inclusion, and
      paucity of cytoplasmic organelles. Its axon synapses around other nigral
      dendrites. The presence of these neurons was correlated with the efferent
      projections and function of the substantia nigra.

PMID- 18631582
TI  - Synapses in the rat substantia nigra.
AB  - The composition and organization of the input to the rat substantia nigra were
      studied with the electron microscope. Four distinct types of synaptic boutons
      were described. The first contained small (381 A), clear synaptic vesicles. The
      second type contained the small, clear vesicles and several large, dense-core
      vesicles. The third ending contained large, dense-core vesicles and larger (581
      A) clear vesicles. The fourth ending, found on the axon hillock and other
      terminal boutons, contained slightly elongated, clear synaptic vesicles. The
      presence of these four boutons was discussed in light of the known afferent input
      and neurochemical composition of the substantia nigra.

PMID- 18631583
TI  - Substructural features of pulmonary endothelial caveolae.
AB  - Substructural specializations of the endothelial caveolae of rat lung capillaries
      are described. Dense knobs occur at the place where caveola membrane, diaphragm
      and plasma membrane fuse. Similar structures are seen where caveolae fuse to form
      complex groups and in preparations of isolated caveolae. The appearance of these
      knobs in transverse sections may represent a circular skeletal structure,
      possibly functioning to maintain the patency of the stoma and the integrity of
      the diaphragm. In addition, the inner concave surface of the caveola membrane
      contains regularly spaced globular structures, possibly enzyme clusters or
      binding sites. This interpretation is supported by the finding that the
      distribution of lead phosphate deposits (formed on reaction of caveolar 5'
      nucleotidase with AMP in the presence of Pb(N0(3))(2)) corresponds with the
      spacing of globular structures. These substructural features of caveolae are
      considered with reference to the ability of caveolae to metabolize circulating
      vasoactive substances.

PMID- 18631584
TI  - Permeability of tarsal sensilla in the tick Amblyomma americanum L. (Acarina,
      Ixodidae).
AB  - Ticks were submerged in silver-protein solution, prior to fixation for electron
      microscopy, in order to trace the pathway of molecules in supposed tarsal
      chemoreceptors. Sensilla with radially arranged cuticular canals (100-200 A in
      diameter) leading to the centrally located dendrites show silver granules inside
      the canals and in the central lumen, thus directly making contact with the
      dendrites. Sensilla with large, plugged pores (1200 A) exhibit an accumulation of
      silver granules in the pore openings but no granules (about 50 A in diameter)
      were observed penetrating into the lumen. Apparently silver granules could
      diffuse in, but not through the material which suspends the pore plugs. It is
      suggested that this material corresponds to the 'pore tubules' in insect
      olfactory sensilla and that it may play an essential role in transmitting a
      chemical stimulus from the environment to the dendrites.

PMID- 18631585
TI  - Champs morphogenetiques mis en evidence par l'etude au microscope electronique a
      balayage des soies au niveau des pattes d'abeilles (apoidea, megachilidae).
AB  - The hairs covering the legs of several species of female megachilid bees are
      arranged in imbricated fields. At the boundaries of these fields, either the
      hairs show a morphology intermediate between those of the contiguous fields, or
      there is a narrow strip with an irregular mosaic of several hair types. It is
      suggested that: 1. The structure of the hairs may be determined by the territory
      in which the trichogenous cell is located. 2. Some morphogenetic fields are
      bidimensional and cross the segmentary boundaries. The name 'regional fields' is
      proposed for them. 3. The regional fields may be modulated within each segment
      into which they extend.

PMID- 18631586
TI  - [Not Available].
AB  - The cuticle, the epidermis, the cross-striated muscle cells, their attachments
      and some sensory endings of this planctonic Crustacean, have been observed and
      are briefly described. The twisted system and the differentiation of hexagonal
      patterns have been studied with the electron microscope, mainly in the outer
      levels of the procuticle. Comparisons with other Cuticular patterns and with
      physical systems are discussed.

PMID- 18631587
TI  - The development of a collagenous connective tissue in the locust, Locusta
      migratoria.
AB  - The ejaculatory duct of adult male locusts is surrounded by a thick layer of
      collagenous tissue. It starts to develop during the second instar when a group of
      cells come to lie adjacent to the basal regions of the epidermal cells which form
      the duct. From the fourth instar onwards, connective tissue is present between
      these cells. The matrix contains many collagen fibrils, some of which are very
      large and of irregular cross section. The banding periodicity is about 625 A. The
      cells differentiate into typical fibroblasts with highly dilated rough
      endoplasmic reticulum and small Golgi complexes. In the sexually mature adult,
      the cells are smaller and appear less active.

PMID- 18631588
TI  - The sarcolemma of Aplysia smooth muscle in freeze-fracture preparations.
AB  - Smooth muscle cells in the sheath covering the visceral ganglion of Aplysia
      californica were examined with the techniques of freeze-fracture and conventional
      electron microscopy. The sarcolemma of these muscle cell invaginates to form
      myriad caveolae that have an intrinsic marker within their membrane. This
      intrinsic structure of the caveolar membrane is revealed by freeze-fracture and
      consists of rows of large particles in the outer half and matching grooves on the
      complementary inner half of the membrane. In thin plastic sections, parallel
      striations or shelves within the caveolar membrane appear to be the equivalent of
      the particles and grooves of the fractured membrane. Physical fixation of some
      specimens by rapid freezing in supercooled liquid nitrogen or in liquid helium
      suggests that in their natural state, the caveolar ostia are not uniform in size
      and that at any given moment a number of caveolae are flattened. When segments of
      the connective nerves which link the visceral ganglion to the cephalic ganglia
      are stretched in vitro two to three times their in situ length, the caveolae lose
      their invaginated shape and are fully exposed to the extracellular space. The
      caveolar membrane, so stretched, is pulled into the line of fracture with the
      result that the large particles rather than the ostia appear on the cleaved
      surface. This flattening of the caveolae is reversible and suggests that they
      might serve as miniature stretch-receptors within the membrane of the smooth
      muscle cells. The caveolae are accessible to extracellular horseradish peroxidase
      but do not appear to pinocytose the protein.

PMID- 18631589
TI  - Plant virus uncoating as a result of virus-cell wall interactions.
AB  - The fate of tobacco rattle virus (TRV) particles was studied after leaf panel
      infiltration. It was found that end-on virus attachment to cell walls of hosts
      (Nicotiana tobacum L. var. Xanthi-nc) and nonhosts (Zea mays L.) occurred, and
      that a virus degradative phase commenced immediately after attachment. Length of
      TRV particles changed drastically following infiltration. The normal length of
      the particles became smaller than that of the particle carrying the coat protein
      gene (108 nm). Five days after infiltration, no particles could be detected on
      the walls of cells bordering intercellular spaces. Virus attachment and
      degradation was thus shown to be nonspecific. Autoradiographic studies showed
      that iodinated viral coat protein or a breakdown product of this protein ((125I
      label in coat protein of complete virus) and not virus particles are transported
      to the vascular bundle after infiltration. Tobacco mosaic virus (TMV) and TRV
      were infiltrated into their respective local lesion hosts. There was an initial
      time interval early after the infiltration during which wounding (pin pricking)
      the infiltrated leaf panels resulted in local lesion formation. The results are
      discussed with regard to the phenomenon of viral genome release in the plant
      virus infection process.

PMID- 18631590
TI  - Translational studies with turnip yellow mosaic virus RNAs isolated from major
      and minor virus particles.
AB  - The major and minor nucleoprotein components in turnip yellow mosaic virus (TYMV)
      preparations have been fractionated by four cycles of CsCl gradient equilibrium
      centrifugations. RNAs isolated from the various fractions were translated in a
      rabbit reticulocyte cell-free system. Three classes of RNAs were studied: genomic
      RNA with an Mr of 2.0 x 10(6), the subgenomic coat protein messenger with an (r)
      of 2.4 x 10(5) (H. Guilley and J. P. Briand, 1978, Cell15, 113-122) and RNA
      molecules of intermediate sizes. Genomic RNA is found in the major TYMV
      components. These particles do not contain the coat protein messenger. The latter
      messenger has mainly been detected in two types of minor components, those which
      have an RNA content exceeding that of the major TYMV virions and particles which
      contain the coat protein messenger as their sole RNA constituent. RNAs of
      intermediate sizes are found in minor components less dense than the major
      particles; the full-length translational products of these RNAs and of genomic
      RNA overlap with one another and share a common NH2 terminus. It is concluded
      that a number of intermediate-sized RNAs and the genomic RNA have a common site
      for initiation of translation located close to their 5'-termini.

PMID- 18631591
TI  - Circularity of the ribonucleic acids associated with cadang-cadang disease.
AB  - The ribonucleic acids, ccRNA-1 and ceRNA-2, associated with cadang-cadang disease
      are circular single-stranded molecules comprising 310 +/- 3 nucleotides and 438
      +/- 5 nucleotides, respectively; their molecular weights are estimated to be 1.05
      and 1.49 x 10(5) daltons. Therefore ceRNA-2 appears not to be a dimer of ccRNA-1,
      although it is known to have nucleotide sequences in common with ccRNA-1.
      Differences in the native structure of the two RNAs as determined by length
      measurements may account for previously described differences in their
      properties. Both RNAs resemble viroids, but ccRNA-1 is smaller, and ceRNA-2 is
      larger, than the viroids which have been characterized.

PMID- 18631593
TI  - Iodination of satellite tobacco necrosis virus (STNV) for crystallographic
      structure determination.
AB  - Attempts to modify satellite tobacco necrosis virus (STNV) chemically to obtain
      heavy atom derivatives have shown that the virus particle is chemically very
      inert. Of the many modification methods employed (resulting in formation of
      covalent bonds), iodination was the only one to provide useful derivatives. A
      derivative of STNV containing 2.3 iodine atoms per protein subunit was prepared
      and crystallized. X-ray data were collected on this heavy atom derivative. The X
      ray diffraction pattern from the derivative crystals showed significant intensity
      differences compared to that of the native crystals. Modified peptides of
      iodinated STNV were isolated and the sites of modification were determined. Of
      the 2.3 iodine atoms found to react with STNV on the average, 1.5 atoms were
      bound to one of the four histidine residues and the residual 0.8 iodine atoms
      were observed bound to at least two of the four tyrosine residues.

PMID- 18631594
TI  - Unstable infectivity and sedimentable ds-RNA associated with lettuce speckles
      mottle virus.
AB  - Infectivity associated with extracts of lettuce speckles mottle virus (LSMV)
      infected tissues is unstable and is susceptible to short periods of aging in
      vitro or low concentrations of RNase. Infected leaves extracted using phenol
      yielded greater infectivity than comparable tissue extracted with buffer. No
      typical virus particles were observed in infected tissues or clarified
      preparations, but 50- to 70-nm spherical membranous particles were observed
      associated with the tonoplast in vacuoles of infected cells. Polyacrylamide gel
      electrophoresis of nucleic acids from infected tissue and LSMV-clarified
      preparations revealed abundant double-stranded RNA (ds-RNA) in both preparations.
      A species of LSMV-specific single-stranded RNA (ss-RNA) was also present in LSMV
      bentonite-clarified preparations. Infectivity was associated only with the ss-RNA
      fraction. Quantitative isolation of ds-RNA from whole tissue and clarified
      preparations showed the majority of the ds-RNA was recovered from the bentonite
      clarified fractions, and this RNA appeared to be associated with a relatively
      small structure of a low buoyant density. These data suggest that LSMV lacks a
      functional coat protein and the sedimentable dsRNA fraction from LSMV-infected
      tissues more likely contains a viral-specific replication site and not true virus
      particles.

PMID- 18631595
TI  - Ultrastructural features of the parenchyma of young leaves of Datura stramonium
      L. systemically infected with potato virus X.
AB  - Mosaic symptoms were observed on the tip parts of upper leaves of Datura
      stramonium L. (2-3 cm in length), systemically infected with potato virus X
      (PVX); symptoms were absent on basal parts of the same leaves. Virus-like
      particles were not observed in the parenchyma cells of the basal parts lacking
      symptoms. Considerable retraction of the plasmalemma from the cell wall and the
      appearance of vesicles and tubules between them were the most characteristic
      features of such cells. In the tip parts of the leaves with mosaic symptoms,
      numerous PVX particles were observed in many parenchyma cells, where they were
      dispersed in the cytoplasm or grouped in aggregates. As a rule the dispersed PVX
      virions were associated with specific laminated inclusions. Sometimes virions
      appeared in areas of the cytoplasm subjected to local autolysis. The tonoplast
      was often disturbed in infected cells, and virus particles were released into a
      central vacuole.

PMID- 18631596
TI  - The genome of a baculovirus infecting Tipula paludosa (Meig) (diptera): a high
      molecular weight closed circular DNA of zero superhelix density.
AB  - A characterization of the genome of a baculovirus infecting the diptera, Tipula
      paludosa Meig, is presented here. It appears to be a double-stranded closed
      circular DNA. The supercoiled structure has been visualized by electron
      microscopy. The relaxed molecules have a contour length of 51.2 +/- 1.5 mum which
      corresponds to a molecular weight of 92 x 10(6) daltons, by taking the value of
      6.4 x 10(6) daltons for PM2 DNA used as an internal standard for the spreading.
      T. paludosa baculovirus DNA has a low G + C content of 27%, as estimated from its
      buoyant density in CsCl, uv spectrum, and melting temperature. Its sedimentation
      coefficient in alkaline solution was 294 S, as determined by analytical
      sedimentation.

PMID- 18631597
TI  - The structure of cauliflower mosaic virus: a neutron diffraction study.
AB  - Neutron scattering has been used to determine the organization of cauliflower
      mosaic virus. The virus can be represented by a model that consists essentially
      of a protein shell surrounding and in direct contact with a shell of DNA. Protein
      seems to be present at a low concentration directly beneath the DNA shell, and
      the center of the virion seems to be free of DNA and protein.

PMID- 18631600
TI  - Sequence complementarity of sonchus yellow net virus RNA with RNA isolated from
      the polysomes of infected tobacco.
AB  - Polyribosomal RNA from tobacco infected with sonchus yellow net virus (SYNV)
      contained sequences which hybridized to 125I-labeled SYNV RNA and which were
      complementary to 80 to 100% of the viral RNA genome. The poly(A)-containing RNA
      from polyribosomes was complementary to over 90% of the viral genome but the
      polyribosomal RNA lacking poly(A) hybridized to approximately 40-60% of the
      genome. The kinetics of hybridization of all three fractions are best explained
      by the presence of a single abundance class of viral-complementary RNA. However,
      titration hybridization of poly(A)+ RNA to an excess of SYNV RNA suggested that
      viral-complementary sequences which contain poly(A) may vary in concentration
      over a factor of about fivefold. About 1.5 to 4.6% of the fraction containing
      poly(A), 0.02 to 0.06% of the fraction lacking poly(A) and 0.04 to 0.18% of the
      total polyribosomal RNA was complementary to viral RNA as estimated from the
      kinetics of hybridization. The viral complementary RNA(vcRNA) was heterogeneous
      in size with a modal sedimentation coefficient of 12 S and a profile in sucrose
      density gradients similar to the polyadenylated polyribosomal RNA.

PMID- 18631601
TI  - Behaviour of turnip yellow mosaic virus nucleoproteins under alkaline conditions.
AB  - A modified CsCl density gradient procedure is described by which purified
      preparations of turnip yellow mosaic virus (TYMV) can be fractionated to give 12
      nucleoprotein components. When the B1 nucleoprotein is subjected to pH 11.5-11.6
      in 1 M KCl (conditions under which artificial empty protein shells are formed),
      the apparent radius (r) of the virus increases from about 14.6 to 15.2 nm within
      30 sec. The increase in r is most probably due to swelling of the particles.
      Escape of the RNA from these particles is completed in 3-10 min, while RNA
      degradation continues for at least 30 min. On return to pH 7.0, r returns to
      about 14.6 nm. When any of the minor nucleoprotein fractions containing less than
      the full complement of RNA are subjected to the above conditions, the RNA does
      not escape from the particle. Experiments with the B0 components also showed that
      these particles did not give an increase in r, although the RNA was degraded to
      about the same extent as that of the B1 nucleoprotein.

PMID- 18631602
TI  - Isolation of replicative forms of 3' terminal subgenomic RNAs of tobacco necrosis
      virus.
AB  - Three double-stranded RNAs of molecular weights 2.6 x 10(6), 1.05 x 10(6), and
      0.94 x 10(6) are found to be synthesized during TNV infection of tobacco leaves.
      These double-stranded RNAs, isolated by LiCl fractionation and polyacrylamide gel
      electrophoresis, have been studied using RNA-RNA hybridization and RNase T(1)
      resistant oligonucleotide finger-printing techniques. By these methods all three
      double-stranded RNAs are shown to be viral in origin and the smaller double
      stranded RNA subsets of the larger RNAs. RNase T(1) oligonucleotide mapping of
      the viral RNA shows that both smaller double-stranded RNAs are derived from the
      3' end of the viral genome. The possible role of these small double-stranded RNAs
      as replicative forms for mRNA synthesis and the organization and expression of
      the TNV genome is discussed.

PMID- 18631603
TI  - Translation of tobacco rattle virus RNAs in vitro: four proteins from three RNAs.
AB  - RNAs from the Lisse and PRN strains of tobacco rattle virus were translated in
      nuclease-treated reticulocyte lysates. With both strains, RNA-1 coded for two
      proteins of MW 170,000 and 120,000. Addition of 1-2 mM Mg2+ increased the yield
      of the larger product, apparently by facilitating readthrough of a leaky
      termination codon at the end of the region coding for the smaller protein.
      Experiments with yeast suppressor tRNA indicate that this is not a UAG or UAA
      codon. RNA-2 coded for a protein of the same size as coat protein. A product of
      MW 30,000 was coded by a third RNA (RNA-3) which in the case of PRN TRV had a
      molecular weight of 550,000 and could be separated from RNA-2 by gel
      electrophoresis. Translation of all three RNAs was inhibited by m7GTP. However,
      RNA-1 also directed a low level of m7GTP-resistant synthesis of a 30,000-dalton
      protein which appeared to be identical to the RNA-3 product, and it is suggested
      that RNA-3 corresponds to the 3' end of RNA-1. Thus the strategies of synthesis
      of the non-coat proteins of tobacco rattle and tobacco mosaic viruses appear to
      be similar.

PMID- 18631604
TI  - Aminoacylation and messenger functions of eggplant mosaic virus RNA.
AB  - The predominant RNA of eggplant mosaic virus (EMV) was found to have a molecular
      weight of 1.9 x 10(6) by formamide gel electrophoresis. Electrophoretic analysis
      of virion protein under dissociating conditions revealed two polypeptides, a
      major component of 21,000 daltons, and a minor component of 22,000 daltons. Both
      peptides were present in translation products coded by RNA isolated from virions,
      but the proportion of the 22,000-dalton peptide was higher in products
      synthesized using RNA isolated from EMV-infected Datura leaves as messenger.
      Since the viral RNA showed a marked tendency to aggregate, it is possible that
      these polypeptides were translated from trace amounts of small EMV RNAs present
      as contaminants of the 1.9 x 10(5)-dalton genomic RNA. Although the addition of
      tRNA from infected or healthy Datura leaves, or from wheat germ, stimulated amino
      acid incorporation, no changes were discerned in the profile of cell-free
      translation products after electrophoretic separation. Nonaminoacylated and
      valylated EMV RNA stimulated similar levels of amino acid incorporation, and the
      translation products appeared identical. Valine bound to genomic EMV RNA was not
      donated during protein synthesis.

PMID- 18631605
TI  - The size and topology of single-stranded DNA from bean golden mosaic virus.
AB  - The single-stranded DNA (ssDNA) of bean golden mosaic virus (BGMV) was resolved
      into two components by polyacrylamide gel (2.5%) electrophoresis in 8 M urea and
      by rate-zonal sedimentation in 5-20% alkaline sucrose density gradients. Viral
      DNA, either unfractionated or fractionated and electroeluted from polyacrylamide
      gels, was spread for electron microscopic examination. Unfractionated DNA and the
      slower of the two fractionated components contained predominantly circular
      molecules. The faster component consisted entirely of linear molecules. Circular
      molecules had contour lengths corresponding to 8.0 x 10(5) daltons.

PMID- 18631606
TI  - Citrus exocortis viroid (CEV): Protein alterations in different hosts following
      viroid infection.
AB  - Polyacrylamide-SDS protein profiles of different CEV-hosts (Gynura aurantiaca DC,
      tomato, potato, and "Etrog" citron) as altered by the viroid infection are
      presented. A common feature of leaf protein alteration patterns of all hosts is
      the intensification of two low molecular weight protein bands (Gynura aurantiaca
      DC and "Etrog" citron CEV-P1: 13,700 daltons and CEV-P2:18,000 daltons; tomato
      and potato CEV-P2:12,000 daltons and CEV-P2:16,300 daltons) analogous to those
      described for CEV-infected Gynura aurantiaca. Although the omnipresence of CEV-P1
      and -P2 in all CEV-infected hosts suggests that these proteins may be translation
      products of CEV-RNA or of its complementary strand, the host-dependent size of
      CEV-P1 and -P2 and their presence in naturally senescing Gynura plants strongly
      suggest that neither of the polypeptides are translation products of the CEV-RNA
      or of any mRNA exclusively related to CEV-host interaction.

PMID- 18631607
TI  - Reassembly of particles using the RNA from partially disassembled tobacco mosaic
      virus.
AB  - Controlled alkaline disassembly of tobacco mosaic virus (TMV) results in the
      production of two populations of partially stripped virus. These particles have
      been designated PSV5 and 6 and are the two smallest particles produced during
      alkaline disassembly of TMV. The RNA from these particles was able to reassemble
      with TMV coat protein. The reassembled particles were resistant to ribonuclease
      treatment and sedimented upon sucrose density gradient centrifugation to the same
      position as authentic PSV5 and 6 particles.

PMID- 18631608
TI  - Beet yellow stunt virus in cells of Sonchus oleraceus L. and its relation to host
      mitochondria.
AB  - In Sonchus oleraceus L. (Asteraceae) infected with the beet yellow stunt virus
      (BYSV) the virions are found in phloem cells, including the sieve elements. In
      parenchymatous phloem cells, the virus is present mainly in the cytoplasm. In
      some parenchymatous cells, containing massive accumulations of virus, the
      flexuous rodlike virus particles are found partly inserted into mitochondrial
      cristae. The mitochondrial envelope is absent where virus is present in the
      cristae. A similar relation between virus and host mitochondria apparently has
      not been recorded for any other plant virus.

PMID- 18631609
TI  - Purification and characterization of potato leafroll virus.
AB  - Potato leafroll virus (PLRV) was purified from infected potato (Solanum tuberosum
      L.) with yields of 0.4-0.6 mg/kg of foliage. The virus sedimented as a single
      component of 127 S. An antiserum prepared against purified virus had a maximum
      titer of 1:1024 in agar gel double diffusion tests. PLRV had a buoyant density of
      1.39 g/ml and an estimated nucleic acid content of 28%. The nucleic acid had a
      molecular weight of 2.0 x 10(6) and was degraded by RNase but not by DNase,
      indicating that the PLRV nucleic acid is RNA. The sedimentation coefficient of
      the RNA molecule was 34.5 S and after treatment with formaldehyde, 20.7 S.
      Dissociated coat protein migrated as a single band in polyacrylamide gel
      electrophoresis and the average subunit molecular weight was 26,300. PLRV should
      be considered a member of the luteovirus group.

PMID- 18631610
TI  - Ultraviolet absorption spectra and difference spectra of barley stripe mosaic and
      tobacco mosaic viruses in buffer and sodium dodecyl sulfate.
AB  - Ultraviolet absorption spectra and difference spectra were determined for barley
      stripe mosaic virus (BSMV) virions and protein and for tobacco mosaic virus (TMV)
      virions and protein in buffer and in sodium dodecyl sulfate (SDS). The absorbance
      at 260 nm of BSMV virions disrupted in SDS was 92% of that of intact virions
      after correction for light scattering. The corresponding value for TMV was 76%.
      The decrease in A(260) for BSMV virions upon disruption in SDS was almost
      entirely due to loss of partial hyperchromocity of RNA in the virion. However,
      both the protein and the RNA of TMV were hyperchromic in the virion at 260 nm
      compared to their light absorption after disruption in SDS. The turbidity
      resulting from light scattering was not a linear function of virion concentration
      above 2 mg/ml.

PMID- 18631611
TI  - Diffraction studies of papaya mosaic virus.
AB  - X-ray and optical diffraction studies of the flexuous papaya mosaic virus are
      described. The virus is constructed so that there are 35 coat protein subunits in
      4 turns of the helix. The virus contains about 1410 protein subunits and 6800
      nucleotides and has a molecular weight of about 33 x 10(6). The structure of
      tubes assembled in vitro from coat protein both in the presence and absence of
      nucleic acid resembles that of the native virus.

PMID- 18631612
TI  - The inhibition of papaya mosaic virus assembly related to the effect of cations
      on its RNA.
AB  - Levels of MgCl2 and spermidine which have no effect on the equilibrium of papaya
      mosaic virus (PMV) coat protein, as measured by analytical centrifugation, or on
      its configuration, as judged by circular dichroism, inhibit reconstitution. This
      inhibition can be correlated with enhanced secondary structure of PMV-RNA as
      indicated by melting profiles. It is inferred that the inhibition of PMV assembly
      by NaCl or KCl results from the same effect, which is not found with glycine.

PMID- 18631613
TI  - The assembly of clover yellow mosaic virus and its protein.
AB  - Clover yellow mosaic virus has been reconstituted near neutrality at low ionic
      strength. Reconstitution is stopped by low temperatures or by 0.1 M KCl or 10(-3)
      M MgCl2. Assembly is not confined to homologous RNA. Protein assembles into
      stacked-ring tubes near pH 8.0 or helical structures of two diameters at pH 5.0
      to 5.5.

PMID- 18631614
TI  - 3'-Terminal nucleotide sequence (N = 41) of satellite tobacco necrosis virus RNA.
AB  - To convert satellite tobacco necrosis virus RNA into a template for complementary
      DNA (cDNA) synthesis, a poly(A) tail was added to its 3'-end by means of
      Escherichia coli ATP:RNA adenyltransferase. This product could then be copied by
      avian myeloblastosis virus RNA-dependent DNA polymerase in the presence of
      p(dT)(10) as primer. Under appropriate conditions, cDNA was synthesized
      discontinuously, and limited transcripts were obtained when one or more
      deoxynucleoside triphosphates were omitted from the reaction mixture. "Phased"
      cDNA fragments suitable for sequence analysis were synthesized when (dT)(8)dG,
      (32)P-labeled at the 5'-end, was used as a primer. We report here the sequence of
      the 3'-terminal 41 nucleotides of the viral RNA.

PMID- 18631615
TI  - Hybridization analysis of chrysanthemum stunt viroid with complementary DNA and
      the quantitation of viroid RNA sequences in extracts of infected plants.
AB  - In order to develop a method for the quantitation of viroids in extracts of
      infected plants by hybridization analysis with labeled complementary DNA (cDNA),
      the kinetics of hybridization of chrysanthemum stunt viroid (CSV) with [32P]cDNA
      were investigated. Two buffer systems were used, each with a total cation
      concentration of 0.19 M, with one containing no formamide (Buffer A) and the
      other 40% (v/v) formamide (Buffer B). Initial experiments with Buffer A at 60
      degrees showed that the rate of hybridization of [32P]cDNA was slowest with the
      circular form of CSV, fastest with nuclease S(1)-treated CSV, while linear CSV
      gave an intermediate rate. This variation in rate was considered to reflect the
      variation in residual secondary structure of the three forms of CSV under the
      conditions used. By contrast, the three forms of CSV hybridized with [32P]cDNA at
      essentially the same rate in Buffer B at 50 degrees , conditions under which no
      viroid secondary structure remained. A linear relationship was observed between
      the temperature of hybridization and the log R (0)t (1 2 ) of cDNA:RNA hybrids
      formed in both buffer systems; the rate of hybridization decreased 50-fold as the
      hybridization temperature was decreased from 10 to 25 degrees below the T(m) of
      the hybrids. No such relationship was found when similar experiments were carried
      out using chrysanthemum 7 S RNA and the satellite RNA of cucumber mosaic virus.
      The optimal hybridization conditions of Buffer B at 50 degrees were chosen to
      quantitate the levels of CSV in CSV-infected chrysanthemums and Gynura
      aurantiaca; from the concentrations found in partially purified nucleic acid
      extracts of these plants, it was calculated that CSV sequences were present at
      1.65 and 0.095 mg/kg of plant material, respectively.

PMID- 18631616
TI  - Genome-associated proteins of comoviruses.
AB  - Previously, a protein has been reported to be associated with the RNAs of cowpea
      mosaic virus. Here we present evidence for genome-associated proteins of other
      comoviruses: squash mosaic virus, Echtes Ackerbohnemosaik-Virus, and another
      strain of cowpea mosaic virus. Although the proteins and protein-oligonucleotide
      complexes derived from the RNAs of these viruses showed similar patterns of
      electrophoretic mobility, two-dimensional chromatograms of their tryptic peptides
      were distinct. Chromatograms of peptides from preparations of cowpea mosaic virus
      that were isolated from two hosts were very similar, indicating that the genome
      associated protein may be virus specified. Upon digestion with ribonuclease T1,
      RNAs from the viruses gave rise to a distribution of large oligonucleotides that
      is consistent with the presence of polyriboadenylate.

PMID- 18631617
TI  - A comparative study of the alkaline disassembly of two strains of tobacco mosaic
      virus.
AB  - Exposure of tobacco (Tb) and tomato (Tm) isolates of tobacco mosaic virus (TMV)
      to dilute alkaline solutions (pH > 8.0) at 0 degrees results in disassembly of
      the virus particles. Over the range of pH and NaCl concentration studied, Tm-TMV
      was more sensitive to alkaline conditions than was Tb-TMV. Kinetic analysis
      demonstrates that both isolates disassemble in a stepwise manner and that each
      produces six major intermediate-size particles.

PMID- 18631618
TI  - Subcellular distribution of RNA sequences complementary to sonchus yellow net
      virus RNA.
AB  - RNA isolated from free and membrane-bound polyribosomes of sonchus yellow net
      virus (SYNV)-infected tobacco was hybridized to SYNV RNA. RNA from free
      polyribosomes was shown to be complementary to nearly 100% of the SYNV genome,
      whereas RNA from membrane-bound polyribosomes was complementary to only 40% of
      the SYNV RNA. When RNA derived from the two classes of polyribosomes was
      fractionated by chromatography on oligo(dT)-cellulose, sequences complementary to
      SYNV RNA were present in both bound and unbound fractions. Neither nuclear RNA
      nor poly(A)-containing nuclear RNA from SYNV-infected plants hybridized to SYNV
      RNA. The results suggest that SYNV messenger RNAs are selectively partitioned in
      the cytoplasm and that hybridizing sequences are not abundant in the nuclei of
      infected cells.

PMID- 18631619
TI  - Evidence for different replicative strategies in the plant tombusviruses.
AB  - Analysis of the replicative form (RF) RNAs of three viruses assigned to the
      Tombusvirus group-tomato bushy stunt virus (TBSV), carnation ringspot (CRSV), and
      turnip crinkle (TCV) viruses-indicated that all three have different replicative
      strategies. Viral specific double-stranded (ds)RNAs were isolated from infected
      plant tissues by phenol extraction and cellulose chromatography and analyzed by
      polyacrylamide gel electrophoresis. A single RF species with a molecular weight
      of 3.0 x 10(6) daltons, twofold that of the viral single-stranded RNA, was
      isolated from TCV-infected plants. Two major RF species of 3.0 and 1.0 x 10(6)
      daltons and a minor one with 1.2 x 10(6) daltons were isolated from CRSV-infected
      tissues corresponding to the three genomic RNAs of this multicomponent virus.
      TBSV-infected tissues yielded two replicative intermediate RNA species in
      addition to two dsRNAs with molecular weights of 3.2 and 1.5 x 10(6) daltons.
      Hybridization experiments indicated that both dsRNAs were TBSV-specific. It is
      proposed that the 1.5 x 10(6) dalton dsRNA represents the replicative form of a
      subgenomic fragment of the TBSV RNA with a postulated MW of 0.75 x 10(6) daltons.
      A model for the replication of TBSV is suggested and its possible significance
      discussed.

PMID- 18631620
TI  - Characterization of a viroid associated with avocado sunblotch disease.
AB  - A viroid has been purified from avocado leaves infected by sunblotch disease and
      designated the avocado sunblotch viroid. It is a covalently closed circular RNA
      molecule with a molecular weight lower than that of chrysanthemum stunt viroid
      and citrus exocortis viroid while hybridization analysis with 32P-labeled
      complementary DNA indicated that it is a single RNA species. It could be detected
      as a stainable RNA band on polyacrylamide tube gel electrophoresis of partially
      purified extracts of only two of four avocado isolates with positive symptoms of
      sunblotch disease. However, the viroid was detected in all four isolates by
      hybridization analysis with 32P-complementary DNA; this procedure has potential
      use for the rapid indexing of sunblotch disease since the viroid was not present
      in an isolate of healthy avocado. It has yet to be shown that the viroid is the
      causative agent of sunblotch disease.

PMID- 18631621
TI  - Further genetic analysis of a temperature-sensitive mutant of cowpea mosaic
      virus.
AB  - The two reciprocal hybrids of wild-type cowpea mosaic virus (Sb) and the
      temperature-sensitive mutant N168 were constructed. Symptoms of both hybrids
      differed from those of the parent strains in three differential hosts indicating
      that N168 carries mutations in both components and that symptoms result from
      interactions between components. The occurrence of one or more temperature
      sensitive mutations in the middle-component RNA was confirmed. In vitro
      recombination of the hybrids yielded isolates indistinguishable from the parent
      strains.

PMID- 18631624
TI  - RNA polymerase activity and protein synthesis in brome mosaic virus-infected
      protoplasts.
AB  - RNA-dependent RNA polymerase activity and protein synthesis in brome mosaic virus
      (BMV)-infected and uninfected protoplasts were investigated during the course of
      viral replication. In protoplast homogenates, the membrane-bound RNA polymerase
      activity resistant to actinomycin D was enhanced by BMV infection up to 30-fold
      that found in mock-inoculated protoplasts. The activity was first detected 7 to 8
      hr postinfection. It reached a maximum at around 30 hr postinfection, then
      decreased gradually while virus and the viral antigen in the protoplasts, as
      measured by infectivity and fluorescent antibody staining, respectively,
      continued to increase. The bound enzyme activity was not enhanced by inoculation
      with BMV RNA 3 and/or RNA 4. Four proteins with molecular weights of 120, 110,
      36, and 19.5 x 103 were observed in BMV-infected protoplasts from three plant
      species (a systemic host, a local lesion host, and a nonhost of BMV).

PMID- 18631625
TI  - Evidence for intrastrand complementation in cowpea mosaic virus infection.
AB  - In supplementation tests both middle component (M)-RNA and bottom component (B)
      RNA of cowpea mosaic virus mutant N142 were shown to carry mutations affecting
      local symptoms in bean and cowpea. The M- and B-RNA mutations were separately
      incorporated into the two reciprocal hybrids of N142 and wild-type Sb, designated
      as M142BSb and MSbV142. Mixtures of the two hybrids induced normal local symptoms
      in bean and cowpea as a result of reassortment of components. This was also the
      case with a mixture of MSbV142 and mutant N123. The latter mutant was earlier
      shown to contain a M-RNA mutation for defective symptom expression in bean and
      cowpea. Although both M142BSb and N123 carried M-RNA mutations, mixtures of these
      isolates induced normal local symptoms. Subculturing showed no wild-type virus to
      be present in the inoculated leaves. Thus, intrastrand complementation was
      assumed to result in restoration of normal symptom production. We conclude that
      the results of genetic mixing experiments with multicomponent plant viruses must
      be interpreted cautiously. Subculturing experiments should be performed to
      determine whether restoration of wild-type symptoms results from exchange of
      nonmutated components or from intrastrand complementation.

PMID- 18631626
TI  - Acetylsalicylic acid (aspirin) induces resistance to tobacco mosaic virus in
      tobacco.
AB  - Tobacco cv. Xanthi-nc becomes resistant to tobacco mosaic virus (TMV) and
      produces b proteins when injected with the interferon inducer polyacrylic acid.
      Injection of acetylsalicylic acid (aspirin), benzoic acid, or salicylic acid also
      induces this response in Xanthi-nc. Injection of aspirin, benzoic acid, or
      salicylic acid similarly induces resistance and the formation of new proteins in
      the White Burley and Samsun NN cultivars of tobacco.

PMID- 18631627
TI  - Mosquito baculovirus: sequence of morphogenesis and ultrastructure of the virion.
AB  - The morphogenic sequence of a mosquito baculovirus differed from other
      baculoviruses in that nucleocapsids ca. 180 nm were formed routinely by cleavage
      of nucleocapsids as long as 1 microm. Additionally, in one type of envelopment
      nucleocapsids were enveloped by vesicles which subsequently dissociated. Prior to
      and during virion occlusion the envelope contracted along two-thirds of the
      nucleocapsid resulting in the virion being bulbous at one end. The mature virion
      consisted of an enveloped nucleocapsid with an amorphous, but distinct layer
      between the nucleocapsid and envelope.

PMID- 18631628
TI  - Titration behaviour of three strains of tobacco mosaic virus.
AB  - Hydrogen ion titration curves of the virions and proteins of three strains of
      tobacco mosaic virus (Y-TAMV, U2, and cowpea) were measured in the absence and
      the presence of Ca2+, Mg2+, or Mn2+ ions, and compared with the analogous curves
      for the type strain (vulgare). Extinction coefficients were also measured for all
      four strains' virions and proteins. Y-TAMV is very like vulgare in its cation
      affinities: the virion has probably three groups per protein subunit that titrate
      near neutral pH and significantly bind metal ions; the RNA-free protein has very
      little affinity for Ca2+, although moderate Ca2+ concentrations favour the
      existence of larger polymers. U2 and cowpea strain virions bind cations
      significantly more strongly than do Y-TAMV or vulgare virions: their polymerized
      proteins, too, have significant affinities for Ca2+ ions, which make their
      titration and sedimentation behaviours relatively sensitive to added calcium.
      These cation-binding differences correspond well with the differences between the
      strains' protein sequences. The features common to all four strains are that the
      virions are apparently structurally invariant and have at least one site per
      subunit with Ca2+ affinity in the region of 10(-5)M, while the RNA-free proteins
      lack the high-affinity sites but have weaker Ca2+ affinities in the region of 10(
      3)M. Some of the cation-binding sites probably lie near the central holes of the
      virions.

PMID- 18631629
TI  - Structure of the cauliflower mosaic virus genome. III. Restriction endonuclease
      mapping of thirty-three isolates.
AB  - The sites of various restriction endonucleases were mapped on the DNA of
      cauliflower mosaic virus isolate Cabb B-JI.FspAI,HgiAI,HhaI, andXhoI each cut at
      one site,PstI andPvuII each at two sites,BglII at five sites, andHindIII at nine
      sites;SacP,SmaI, andXbaI did not cut this DNA. These sites and those
      ofBamHI,EcoRI, andSalGI were compared with the sites of these enzymes on the DNAs
      of 32 other CaMV isolates. Considerable variations were found both in numbers and
      map positions of the sites of the restriction enzymes. The significance of this
      variation is discussed.

PMID- 18631630
TI  - Replication of alfalfa mosaic virus RNA: evidence for a soluble replicase in
      healthy and infected tobacco leaves.
AB  - Soluble RNA-dependent RNA polymerases from healthy and alfalfa mosaic virus (AMV)
      infected leaves were purified more than 400-fold from the 100,000g supernatant of
      leaf homogenates, using ammonium sulfate precipitation, Sephadex G-100
      filtration, and chromatography on DEAE Sephadex A25 and P11-phosphocellulose. The
      DEAE-chromatography step eliminated host poly(U)polymerase-like activity,
      cellular RNases, and endogenous RNA, yielding a typical RNA-dependent RNA
      polymerase ("DEAE-enzyme") which was dependent on exogenous RNA. On nondenaturing
      4-30% gradient slab gels, the activity of the enzyme was recovered in two peaks
      containing proteins of 340K and 160K. RNA products were synthesized in the
      presence of the "DEAE-enzyme" from healthy and infected leaves: When an excess of
      AMV RNA was introduced into the reaction mixture, only synthesis of minus strand
      RNA was detected. However, when limiting amounts of AMV RNA were used as template
      some small plus strands were detected, suggesting that synthesized minus strands
      may in turn serve as template. In both cases, the products were partially double
      stranded, and of very heterogenous size. Their size depended on the length of the
      RNA template which in turn varied according to the degree of RNase contamination
      of the enzyme fractions. These results are the first demonstration that both
      healthy and AMV-infected tobacco leaves contain a soluble replicase, although its
      possible in vivo role in viral replication is yet to be demonstrated.

PMID- 18631631
TI  - Effect of 2,4-dichlorophenoxyacetic acid on multiplication of tobacco mosaic
      virus in protoplasts from local-lesion and systemic-responding tobaccos.
AB  - Tobacco mosaic virus (TMV) multiplication was markedly enhanced in protoplasts
      from Samsun NN and Xanthi-nc, two local-lesion-responding cultivars, by 2,4
      dichlorophenoxyacetic acid (2,4-D) added to the incubation medium after
      inoculation of the protoplasts. In Samsun, a cultivar which reacts systemically
      to TMV infection, 2,4-D reduced virus multiplication. These findings may explain
      the discrepancy observed between the low virus multiplication in intact tobaccos
      with the N gene and the high titers reached in protoplasts from these plants (in
      the presence of 2,4-D), which were similar to those found in protoplasts from a
      systemic cultivar.

PMID- 18631632
TI  - Microscopy and biology of Uronema gigas, a filamentous eucaryotic green alga, and
      its associated tailed virus-like particle.
AB  - A polyhedral virus-like particle (VLP) 390 nm in diameter was present in large
      numbers in some cells of two cultures of the filamentous eucaryotic green alga
      Uronema gigas. Cells which contained VLPs lacked nuclear membranes and were found
      only in germlings or young filaments. Extracellular particles of similar size and
      identical ultrastructure accumulated slowly over a 2-month period as the alga
      grew in liquid culture. Capsid size and appearance of partially purified VLPs was
      altered in vitro by fixation and pH. A 1-mum-long tail-like appendage with a
      central swelling was observed attached to some particles in vitro and was also
      detected in situ. VLPs accumulated to relatively high concentrations in some
      single-germling subcultures, but were hard to detect in others. No subcultures
      were obtained which failed to produce VLPs. A correlation was detected between
      high VLP productivity and debilitated growth. VLP productivity could be increased
      in a high yielding subculture by a heat shock treatment during the first 7 hr of
      a 2-week growth cycle. Pronase digestion of thin sections of fixed and embedded
      partially purified VLPs indicated that protein was a major component of the
      capsid shell and contents. DNAse treatments of thin sections and X-ray
      microanalysis in the scanning electron microscope suggested VLP-associated DNA.

PMID- 18631633
TI  - Purification and some properties of a double-stranded DNA containing virus-like
      particle from Uronema gigas, a filamentous eucaryotic green alga.
AB  - A scheme has been developed for the recovery and purification of about 50% of the
      390-nm-diameter virus-like particles (VLPs) present in filtered medium in which
      Uronema gigas was grown for 6 to 10 weeks. Purification was assayed by electron
      microscopy of negatively stained samples. Yield of VLPs was low, for example 150
      mug from 8 liters of medium. The purified VLP had the following
      properties:A260/A280 = 1.14 to 1.21;s(20,w) = 6340 +/- 300 S; buoyant density in
      sucrose, 1.30 g/ml. One major polypeptide (MW = 45,000) and up to nine minor
      polypeptides (MW = 26,000 to 64,000) were detected by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The nucleic acid associated with the VLP was
      double-stranded DNA with a buoyant density of 1.719 g/ml in cesium chloride and
      1.436 g/ml in cesium sulfate. Molecules of the DNA were linear with a length of 4
      to 36 mum (MW = 8 to 72 x 10(6)). No modal length was observed. These properties
      distinguish this VLP from other groups of viruses with dsDNA genomes.

PMID- 18631634
TI  - Lack of specificity of virus-stimulated plant RNA-dependent RNA polymerases.
AB  - RNA-Dependent RNA polymerase preparations from tobacco and cowpea plants, either
      uninfected, or infected with tobacco necrosis or cowpea mosaic virus, were tested
      for their capability to bind radioactive viral or other RNAs or polynucleotides.
      The limited binding of up to 30% of all RNAs tested was found to be completely
      nonspecific in regard to any infecting virus, and it was nonspecifically
      diminished by excess of other unlabeled RNAs. These data are in line with our
      previous conclusion that plant viral RNAs are replicated by host enzymes. The
      data also speak against the hypothesis that these enzymes might be modified as a
      consequence of viral infection.

PMID- 18631635
TI  - Purification and some properties of reovirus-like particles from leafhoppers and
      their possible involvement in wallaby ear disease of maize.
AB  - Reovirus-like particles, occurring in association with viroplasms, crystalline
      arrays and tubules, in the cytoplasm of Cicadulina bimaculata capable of inducing
      wallaby ear disease in maize, were purified from the insects by differential
      centrifugation, treatment with the nonionic detergent, Nonidet P-40, and sucrose
      density gradient centrifugation. The purified particles have a double-shelled
      icosahedral structure about 70 nm in diameter with external projections (A
      spikes) about 10 nm long located at the 12 vertices. These intact particles (IPs)
      are morphologically similar to those of Fiji disease virus (FDV), but are more
      stable. Cores were produced by enzymatic digestion of IPs with alpha
      chymotrypsin. The cores are icosahedra about 57 nm in diameter with projections
      (B spikes) located at the 12 vertices, resembling those of FDV and cytoplasmic
      polyhedrosis virus. Immunization of a rabbit with purified IPs resulted in the
      production of antibodies specific to IPs, cores, and dsRNA. Immunoelectron
      microscopic investigations revealed that there is no relationship between this
      virus and FDV, maize rough dwarf, oat sterile dwarf, pangola stunt, and rice
      ragged stunt viruses, all members of the genus Fijivirus in the family
      Reoviridae. The nucleic acid extracted from partially purified virus was resolved
      into 10 segments by polyacrylamide gel electrophoresis. Reovirus-like particles
      or viroplasms could not be detected in thin sections of maize seedlings colonized
      by C. bimaculata showing wallaby ear symptoms. In the light of these data the
      possible etiology of wallaby ear disease is discussed.

PMID- 18631636
TI  - On the origin of the polyhedral protein of Autographa californica nuclear
      polyhedrosis virus. Isolation, characterization, and translation of viral
      messenger RNA.
AB  - Virus-specific messenger RNA was isolated 24 hr postinfection from Spodoptera
      frugiperda cells infected with Autographa californica nuclear polyhedrosis virus
      (AcNPV) by means of hybridization with viral DNA that was coupled to cellulose.
      Viral mRNA was analyzed on isokinetic sucrose gradients and on polyacrylamide
      gels containing 98% formamide. Viral mRNA was also translated in an in vitro
      protein-synthesizing system derived from wheat germ. One product comigrated with
      purified AcNPV polyhedral protein (MW 30,000) and precipitated with antibodies
      against AcNPV polyhedral protein. These results favor the hypothesis that the
      polyhedral protein is a virus-coded protein.

PMID- 18631637
TI  - Three low molecular weight RNA species detected in tobacco ringspot virus.
AB  - A culture line of tobacco ringspot virus (TRSV) has changed in sedimentation
      properties and does not resolve into components normally found in this virus.
      Virus preparations contain a large proportion of a new type of particle whose
      protein shell is structurally and immunologically the same as normal TRSV capsids
      but encapsidates three species of RNA with molecular weights of approximately
      114,000, 245,000, and 367,000 daltons.

PMID- 18631638
TI  - The composition of Chloris striate mosaic virus, A geminivirus.
AB  - Preparations of Chloris striate mosaic virus (CSMV) were shown to contain
      circular single-stranded DNA with a molecular weight of 7.1 x 10(5) and a
      polypeptide molecular weight of 92.79 +/- 0.06 x 10(4). The buoyant density in
      CsCl of intact CSMV particles was shown to be 1.35 g.cm(-3). From these data and
      the capsomeric structure of CSMV (T. Hatta and R. 1. B. Francki, 1979,
      Virology92, 428-435) it is concluded that each geminate particle of CSMV has a
      molecular weight of about 3.8 x 10(6) and contains a single molecule of ss-DNA.

PMID- 18631639
TI  - Transfection with baculovirus DNA.
AB  - Purified DNA from the nuclear polyhedrosis viruses of Autographa californica (AcM
      NPV) and Rachiplusia ou (RoMNPV) were found to be infectious in TN-368 cells
      employing the calcium phosphate precipitation technique (F. L. Graham and A. J.
      van der Eb, Virology, 52 ,456-467, 1973). Transfection with AcM NPV produced 3600
      PFU/microg DNA compared to 2900 PFU/mug DNA with RoM NPV. Of eight baculovirus
      DNAs tested, only AcM NPV DNA and RoM NPV DNA could transfect TN-368 cells. The
      in vitro host range of AcM NPV DNA was determined to be the same as AcM NPV
      extracellular virus. AcM NPV Form I DNA was fourfold more infectious in TN-368
      cells than Form II DNA.

PMID- 18631640
TI  - Crystalline cowpea mosaic virus.
AB  - Crystals of Cowpea mosaic virus displaying a high degree of order have been grown
      in two different forms. Hexagonal crystals, space group P6(1)22 or P6(5)22 with a
      = 450 A and c = 1038 A containing six virus particles per cell, have been grown
      in sodium citrate buffer at pH 4.9. Each particle has four nearest neighbors at
      284 A. Cubic crystals, with space group I23 and a = 308 A , containing two
      particles per cell were grown from ammonium sulfate at pH 4.9. In the cubic
      crystals, the tetrahedral subgroup of the icosahedral particle symmetry is
      expressed as part of the crystal lattice, with each particle occupying
      tetrahedral crystallographic positions. Contacts of 268 A occur between particles
      in contact along threefold icosahedral symmetry axes.

PMID- 18631641
TI  - Virus-like particles in the ovary of an ichneumonid wasp: Purification and
      preliminary characterization.
AB  - Virus-like particles have been isolated from the oviducts of a parasitoid wasp,
      Hyposoter exiguae (Hymenoptera: Ichneumonidae). Particles are readily purified by
      centrifugation on either Ficoll or sucrose gradients. Double-stranded circular
      DNA isolated from purified particles is heterodisperse in terms of molecular
      weight; none of the molecules are sufficiently large to code for the aggregate of
      structural proteins comprising the particles. Preliminary Southern blot
      hybridization data suggest that there is minimal sequence homology between the
      different size classes of DNA examined.

PMID- 18631642
TI  - Translation of potyvirus RNA in a rabbit reticulocyte lysate: reaction conditions
      and identification of capsid protein as one of the products of in vitro
      translation of tobacco etch and pepper mottle viral RNAs.
AB  - RNAs of pepper mottle virus (PeMV) and tobacco etch virus (TEV) were efficient
      messengers when translated in the rabbit reticulocyte lysate system. Viral RNA
      (39 S) isolated from sucrose density gradients stimulated [35S]methionine
      incorporation into products precipitated by trichloroacetic acid 15- to 20-fold
      over endogenous background levels. Optimal reaction conditions for in vitro
      translation contained 2 mug RNA/30 mul reaction assay, 0.8-1.0 mM magnesium ions,
      and 100-125 mM potassium ions. Labeled products from the translation of TEV and
      PeMV show distinct electrophoretic patterns on sodium dodecyl sulfate
      polyacrylamide gradient gels (PAGE). The major products of TEV translation had
      estimated sizes of 87 x 10(4) daltons (87 kd), 85, 54, 49, and 30 kd. PeMV-RNA
      stimulated the synthesis of 90-, 77-, 68-, 49-, and 33-kd proteins. The 30-kd
      protein for TEV and the 33-kd protein for PeMV were identified as capsid protein
      on the basis of estimated size on PAGE, serological reaction, and peptide
      mapping. The strategy of the in vitro translation of potyvirus RNA is discussed.

PMID- 18631643
TI  - The site of initiation of rod assembly on the RNA of a tomato and a cowpea strain
      of tobacco mosaic virus.
AB  - Genome RNA of a tomato (T) and a cowpea (Cc) strain of tobacco mosaic virus
      (TMV), as well as RNA of the short particles of cowpea strain, were tritium
      labeled at the termini. Chromatographic analyis of the alkali-hydrolysate of
      these RNAs showed that they all have A(OH) at the 3'-terminus and are capped with
      m7G ppp at the 5'-terminus. The site of initiation of rod assembly for these
      strains was determined by sequential reconstitution of virus rods with proteins
      of two different strains followed by examination of distribution of the proteins
      on the reconstituted rods by electron microscopic serology. The initiation site
      on T-RNA was located at the same position as that of a common strain previously
      studied, being about 800 nucleotides away from the 3'-terminus. In contrast, the
      initiation site on Cc-RNA was found to be much closer to the 3'-terminus, only
      about 320 nucleotides away from the terminus, and hence within the coat protein
      cistron. The results showed that the internal initiation and the bidirectional
      elongation are a universal mechanism of assembly among TMV strains, but different
      strains may use different initiation sites. The location of the initiation site
      of the cowpea strain explained why the coat protein messenger RNA of this strain,
      but not that of the common and the tomato strains, is encapsidated to form short
      particles.

PMID- 18631644
TI  - Autographa californica nuclear polyhedrosis virus-induced proteins in tissue
      culture.
AB  - The multiplication of Autographa californica nuclear polyhedrosis virus was
      studied in Trichoplusia ni and Spodoptera frugiperda insect cell lines. Using
      pulse labeling, 18 viral-induced proteins were identified by polyacrylamide gel
      electrophoresis. Based on infectivity curves and protein synthesis studies,
      replication could be divided into four phases. During the early phase of
      infection, four viral-induced proteins with molecular weights of 45, 35, 34, and
      31 thousand daltons could be detected. Maturation of the nonoccluded form of the
      virus and synthesis of 10 viral-induced proteins with molecular weights of 67,
      61, 49, 41, 39, 26, 24, 22, 21, and 16 thousand daltons were first detected
      during the intermediate phase of replication, 10 to 16 hr postinoculation (p.i.).
      During the transitional phase from nonoccluded to occluded virus formation (16 to
      24 hr p.i.), four additional viral-induced proteins could be detected with
      molecular weights of 33, 27, 15.7, and 15 thousand daltons. No additional viral
      induced proteins were detected during the late phase of occluded virus formation.
      Post-translational cleavage was not detected in pulse-chase experiments. The
      addition of varying concentrations of NaCl did not selectively inhibit cellular
      protein synthesis.

PMID- 18631645
TI  - Changes in the organization of bromegrass mosaic virus in response to cation
      binding as probed by changes in susceptibility to degradative enzymes.
AB  - The swelling at alkaline pH and the sensitivity of bromegrass mosaic virus to
      degradative enzymes are less in the presence of moderate concentrations of KC1
      than at low salt concentration. The virus can be efficiently stabilized above
      neutral pH by divalent metal cations, especially Ca2+, but this effect is
      antagonized by KC1. Polyamines also can stabilize the virus, but the salt
      concentrations for optimal protection of the viral RNA and protein moieties are
      then different, as judged by their susceptibility to degradative enzymes. These
      changes in the structural organization of the virus revealed by proteases and
      pancreatic ribonuclease as accessibility probes complement the data from neutron
      scattering studies. On the basis of these studies, a tentative model is proposed
      to account for the polymorphism of BMV in various ionic environments.

PMID- 18631646
TI  - The identification, mapping, and characterization of mRNA for P66, a cauliflower
      mosaic virus-coded protein.
AB  - Turnip leaves infected with cauliflower mosaic virus accumulate variable amounts
      of a nonvirion protein of 66,000 MW. Tryptic fingerprint analysis showed that
      this protein is probably not related to the major virus coat protein (37,000 MW).
      RNA extracted from infected leaves directs the synthesis of a 66,000 MW protein,
      P66, in a wheat germ protein-synthesizing system. P66 synthesis in vitro could be
      arrested by prior hybridization of infected leaf RNA to viral DNA restriction
      fragments indicating that P66 is encoded by the virus genome and specifically by
      EcoRI fragment b. RNA coding for P66 sediments at about 18 S, binds, in part, to
      oligo dT-cellulose, and is sensitive to 7-methyl-GTP inhibition.

PMID- 18631647
TI  - Comparative cytology of nine isolates of cauliflower mosaic virus.
AB  - The cytology of nine isolates of cauliflower mosaic virus was compared by light
      and electron microscopy. Differences noted among the isolates were: the size of
      cytoplasmic inclusion bodies, frequency of virions occurring free in the
      cytoplasm as opposed to those in inclusions, the ratio of virions to the amount
      of matrix protein in inclusions, and intraplastidial inclusions induced by one of
      the isolates. It was concluded that these four cytological features are
      expressions of the viral genome rather than the host. One of the isolates induced
      different sized inclusions in two different hosts.

PMID- 18631648
TI  - Isolation and properties of the inclusion bodies of cauliflower mosaic virus.
AB  - In an attempt to isolate new gene products of cauliflower mosaic virus a
      procedure was developed for isolation of the cytoplasmic inclusion bodies induced
      by the virus. Two types of inclusions, the relative ratios of which vary with
      virus strain, were obtained. One type was the native, vacuolated inclusion
      encountered in sections of tissue observed with the electron microscope. It
      contains virus particles. A second, granular type of inclusion body is devoid of
      virus. It consists wholly of electron-dense material that resembles the matrix
      material of the native inclusion body. Granular inclusions consist of a single
      55,000-dalton protein which is also a major constituent of the native vacuolated
      type. This protein is not antigenically related to the virus.

PMID- 18631649
TI  - Structural analysis of the matrix protein from the nuclear polyhedrosis virus of
      Heliothis zea.
AB  - Polyhedrin from the nuclear polyhedrosis virus of Heliothis zea was analyzed.
      Alkali-solubilized polyhedrin consists of a 12 S aggregate of 27,000 MW subunits.
      Results from chemical crosslinking experiments suggest that 12 subunits are
      present in the 12 S aggregate. In isoelectric focusing gels, the aggregate
      migrates as a single entity with an isoelectric point of 5.9. Under denaturing
      conditions, four charge isomers of the subunits are revealed. The presence of
      alkaline protease activity in the Heliothis virus is confirmed.

PMID- 18631650
TI  - Radioimmunoassay analysis of baculovirus granulins and polyhedrins.
AB  - Granulin and polyhedrin proteins were purified by preparative sodium dodecyl
      sulfate (SDS)-polyacrylamide gel electrophoresis from the baculoviruses
      Autographa californica, Rachiplusia ou, Heliothis zea, Heliothis armigera,
      Trichoplusia ni, and Spodoptera frugiperda. Antisera were raised against
      Autographa californica (Ac) polyhedrin and Trichoplusia ni (Tn) granulin and
      analyzed for homologous and heterologous immunoreactivity by immunodiffusion and
      radioimmunoassay (RIA). Ac polyhedrin and Tn granulin antisera recognized
      antigenic determinants on several baculovirus polyhedrin and granulin proteins
      even though the heterologous proteins had different immunoreactivities when
      compared by competition radioimmunoassay. Antigenic differences among granulin
      and polyhedrin proteins were also detected by altered slopes of the competition
      reaction curves. Antiserum raised against Ac polyhedrin which was purified in the
      presence of SDS was tested by competition RIA for its ability to detect and react
      with native polyhedrin produced in the infected TN-368 cells. Ac polyhedrin
      antiserum had similar if not identical ability to bind to native polyhedrin and
      to polyhedrin purified in the presence of SDS.

PMID- 18631651
TI  - Restriction enzyme cleavage maps of the DNA of two cauliflower mosaic virus
      isolates.
AB  - To provide a physical basis for the functional mapping of the cauliflower mosaic
      virus (CaMV) genome, restriction enzyme cleavage maps of the DNA of CaMV isolates
      NY8153 and CM4-184-OS (a variant of CM4-184) were constructed. CM4-184-OS DNA
      contained five EcoRI, eight HindIII six BglIII, and two BamHI cleavage sites,
      while NY8153 DNA contained one additional HindIII site and one fewer EcoRI site.
      Fragments were ordered by examination of multienzyme and partial digests. The
      resulting maps revealed that the CM4-184-OS genome was 5.5% smaller than that of
      NY8153, because CM4-184-OS was deleted for 463 +/- 10 base pairs including the
      HindIII site at 0.427 map unit (relative to a common EcoR1 site) and the S1 site
      at 0.45 map unit on NY8153 DNA. Since the deleted region did not include the two
      BamHI sites, this variant of the CM4-184 isolate is different from the John Innes
      variant of CM4-184 (R. Hull, and S. H. Howell, Virology 86, 482-493, 1978) which
      is deleted for a different, but overlapping region of the CaMV genome.

PMID- 18631652
TI  - Gene mapping of cytoplasmic polyhedrosis virus of silkworm by the full-length
      mRNA prepared under optimized conditions of transcription in vitro.
AB  - Viral mRNA synthesis by the RNA polymerase associated with purified cytoplasmic
      polyhedrosis virus (CPV) was studied. The formation of full-length mRNA products
      was facilitated by including in the reaction mixture 100 mM sodium acetate, high
      concentrations of ribonucleoside triphosphates, and proteinase K. The 10
      different species of CPV mRNAS were resolved into 9 discrete RNA bands by agarose
      gel electrophoresis at pH 3.5 in buffer containing 7 M urea. Each purified viral
      mRNA hybridized specifically to one of the viral genome segments which were
      separated by polyacrylamide gel electrophoresis into the 10 species of dsRNA. The
      relationship between the genome segments and their cognate mRNAs synthesized in
      vitro is thus established. Under optimal conditions of mRNA synthesis each of the
      genome segments was transcribed at a similar rate as determined from the yield of
      individual separated mRNA species. A recycling model of genome-associated RNA
      polymerase for viral transcription is discussed.

PMID- 18631653
TI  - X-ray microanalysis of leaf tumors from maize plants experimentally infected with
      maize rough dwarf virus: scanning and transmission electron microscopic study.
AB  - X-Ray microanalysis, performed by both scanning and transmission electron
      microscopes equipped with energy-dispersive spectrometers (EDS), was used to
      analyze the element distribution in phloem tumors induced by maize rough dwarf
      virus (MRDV) in Zea mays L. The content of both Si and Ca was lower in tumors
      than in the nontumoral surrounding tissues. The Si content increased in old
      tumors where this element was mainly concentrated in the trichomes growing at
      their surface. The peaks of other detectable elements, P, K, and S, were higher
      in tumor than in nontumor tissues. The distribution of inorganic cations in the
      cells was also studied by the potassium pyroantimonate (KPA) precipitation
      technique. The KPA precipitates have proved to be primarily of calcium salts and
      they occurred quite frequently in the cells at the tumor periphery.

PMID- 18631654
TI  - Protease degradation of Autographa californica nuclear polyhedrosis virus
      proteins.
AB  - The Autographa californica nuclear polyhedrosis virus (Ac-NPV) occlusion bodies
      produced in vivo contained a protease which degraded occlusion body matrix
      protein and polypeptides of enveloped nucleocapsids during alkaline dissolution.
      The protease activity was required for complete dissociation of occlusion body
      matrix protein from the viral membrane during alkali liberation of the virus from
      occlusion bodies. In addition protease activity was required for the subsequent
      removal of the viral membrane from the nucleocapsids by Nonidet P40 treatments.
      Protease activity was not detected in occlusion bodies isolated from tissue
      culture cells or heat-treated (80 degrees , 45 min) occlusion bodies isolated
      from insect larvae. When occluded Ac-NPV virions were purified in the absence of
      protease activity, 26- polypeptides with molecular weights ranging from 115,000
      to 15,000 were identified. The occlusion body matrix protein had an apparent
      molecular weight of 33,000.

PMID- 18631655
TI  - Protein synthesis in cells infected by Autographa californica nuclear
      polyhedrosis virus (Ac-NPV): the effect of cytosine arabinoside.
AB  - Twenty-two virion polypeptides (VP) were detected reproducibly when the occluded
      form (OV) of [35S]methionine-labeled Ac-NPV, purified from polyhedral inclusion
      bodies (PIB), was analyzed by polyacrylamide gel electrophoresis and
      autoradiography. Ten of the VPs and the polyhedral protein (PP) were
      phosphorylated and 6 VPs were glycoproteins. Purified, nonoccluded virus (NOV)
      revealed 25 polypeptides. During a single cycle of virus replication, the
      synthesis of 33 infected cell polypeptides (1CP) was detected in different
      relative proportions at different times. They were arbitrarily designated as
      early (0-12hr), middle (12-18 hr), and late 18-24 hr) polypeptides. Most of the
      middle and late proteins seemed to be viral structural proteins. Rapid post
      translational cleavage of IPCs was not observed; however, pulse-chase experiments
      revealed post-translational modifications of at least four polypeptides.
      Inhibition of DNA synthesis at the time of infection did not prevent the
      synthesis of ICPs, VPs, or the formation of PIBs. Progeny PIB from both control
      and cytosine arabinoside (Ara C)-treated cells that were infected with
      radiochemically pure [3H]thymidine-labeled NOV contained parental virus DNA.
      Electron micrographs of thin sections showed that, whereas PIBs from control
      cultures contained complete virions, those from Ara (C-treated cells contained
      both full and empty virus.

PMID- 18631656
TI  - Tomato DNA contains no detectable regions complementary to potato spindle tuber
      viroid as assayed by solution and filter hybridization.
AB  - A previous report (Hadidi et al. (1976) Proc. Nat. Acad. Sci. USA73, 2453-2457)
      has suggested that potato spindle tuber viroid (PSTV) RNA contains sequences
      complementary to the DNA of its host and, to a lesser extent, to the DNA of some
      nonhost species. Our studies indicate, however, that the apparent hybridization
      between (125)I-labeled PSTV and tomato DNA which can be observed in both solution
      and filter hybridization experiments is a consequence of the hybridization of
      host RNAs (mostly ribosomal) which are minor contaminants of the polyacrylamide
      gel-purified viroid preparations. When the level of these contaminants is reduced
      by further purification of the viroid in gels containing 8 M urea, no
      hybridization to tomato DNA could be detected. Thus, if sequence homology exists,
      it must be very minimal and its detection is beyond the capabilities of the
      methods employed.

PMID- 18631657
TI  - Tomato DNA contains no detectable regions complementary to potato spindle tuber
      viroid as assayed by Southern hybridization.
AB  - DNA was isolated from crude nuclear pellets prepared from Rutgers tomato plant
      leaf tissue from both potato spindle tuber viroid (PSTV)-infected and uninfected
      plants. Following digestion by the DNA restriction enzymes EcoRI, XbaI, or BamHI,
      the DNA was fractionated by agarose gel electrophoresis, transferred to
      nitrocellulose filters, and incubated with a variety of 125I-labeled RNA probes
      under conditions which permit hybridization. Analysis of autoradiogram patterns
      and fingerprints of the RNA recovered from individual bands following
      hybridization of the three tomato cytoplasmic ribosomal species, 5, 18, and 26 S,
      permitted us to construct a consistent restriction map about 8800 base pairs in
      length containing the 18 and 26 S species and to demonstrate that the 5 S gene
      clusters are not linked to the 18 and 26 S regions and themselves have a repeat
      length of about 350 base pairs. These studies formed the background for a search
      for hybridization between 125I-labeled PSTV and DNA from uninfected and PSTV
      infected tomato plants. Significant hybridization was observed when
      conventionally prepared viroid was used as the probe in Southern hybridization
      experiments. However, fingerprint analysis of the RNA recovered from these bands
      demonstrated that this hybridization was due to the presence of ribosomal RNA
      species in the viroid preparation. When the viroid was subjected to further
      purification steps (electrophoresis in gels containing 8 M urea) prior to
      hybridization, all traces of hybridization due to host contaminants disappeared
      and no viroid-specific bands could be detected, even upon prolonged exposure of
      the autoradiograms. Under these same hybridization conditions, we could detect as
      little as one-quarter copy of a gene 550 base pairs in length.

PMID- 18631658
TI  - Role of accessory salivary glands in aphid transmission of barley yellow dwarf
      virus.
AB  - Barley yellow dwarf virus (BYDV) was consistently observed in the basal lamina
      and in plasmalemma invaginations only of accessory salivary glands in each of 20
      aphids (Sitobion avenae) reared on oats infected with the MAV or RPV isolates of
      BYDV. Virus particles were not found in any of 13 aphids reared in parallel on
      healthy oats. The MAV isolate was identified in aphids by indirect labeling with
      ferritin-conjugated antibody. Virus particles were also observed within
      cytoplasmic vesicles and intracellular canals that drain the accessory gland in
      all aphids reared on oats infected with MAV, which is transmitted by S. avenae,
      but in none of the aphids reared in parallel on oats infected with RPV, which S.
      avenae does not transmit. Visualization of only transmissible virus within
      accessory gland cytoplasmic structures indicates that the plasmalemma may be a
      site regulating virus uptake by the salivary gland. Presence of virus in
      intracellular canals and in coated pits and vesicles adjacent, to canals suggests
      possible transport mechanisms out of the accessory gland. The results are
      compatible with a virus-cell receptor mechanism for transmission specificity
      between luteoviruses and aphid vectors, and they suggest a route through aphids
      for viruses transmitted in the circulative manner.

PMID- 18631659
TI  - Involvement of the host RNA polymerase in the early transcription program of
      Caulobacter crescentus bacteriophage phiCdl DNA.
AB  - The host RNA polymerase appears to be involved in the early transcription program
      of the Caulobacter crescentus bacteriophage phiCdl. The addition of rifampicin
      early after infection inhibited the production of phage, whereas phiCdl
      production was not inhibited by the addition of rifampicin at any time after
      infection of a rifampicin-resistant host. In addition, we found that a rifampicin
      resistant RNA polymerase activity dependent on de novo protein synthesis is
      required for late transcription. The region of early phiCdl was mapped by
      hybridizing labeled RNA extracted from phiCdl-infected cells grown in the
      presence or absence of chloramphenicol to HindIII and HpaI restriction fragments
      of the phiCdl genome.

PMID- 18631660
TI  - Multiple small RNA species and the viroid hypothesis for the sunblotch disease of
      avocado.
AB  - Multiple RNA species (ASV(1-5)) ranging in size from about 61,000 to 185,000
      daltons have been detected in association with sunblotch disease of avocado. The
      predominant species, ASV(5), with a molecular weight of 61,000 accumulates to
      concentration approaching 5 S RNA. All RNA species are detected in extracts from
      symptomatic tissue of avocado var. Fuerte but not from asymptomatic tissue of the
      same leaves from which the disease agent can be transmitted to avocado. The
      probability that the predominant ASV(5) species is either the putative sunblotch
      "viroid" or a noninfectious "viroid-related" molecule is discussed.

PMID- 18631661
TI  - Translation of potyvirus RNA in a rabbit reticulocyte lysate: identification of
      nuclear inclusion proteins as products of tobacco etch virus RNA translation and
      cylindrical inclusion protein as a product of the potyvirus genome.
AB  - The translations of tobacco etch virus (TEV) RNA and pepper mottle virus (PeMV)
      RNA in the mRNA-dependent rabbit reticulocyte lysate produced products which
      comigrated with potyviral inclusion proteins on polyacrylamide gels. The TEV RNA
      translation products comigrating with the 49,000 and 54,000 molecular weight TEV
      nuclear inclusion proteins were also immunoprecipitated by antisera specific to
      the nuclear inclusion proteins. The proteolytic peptide map of the comigrating in
      vitro translation products for TEV RNA was similar to that generated by the
      nuclear inclusion proteins. The PeMV RNA translation product comigrating with the
      cylindrical (pinwheel) inclusion protein was immunoprecipitated by antiserum to
      PeMV cylindrical inclusion protein. These results provided direct evidence that
      the inclusions associated with potyviruses consist of virus-coded, nonstructural
      proteins.

PMID- 18631662
TI  - Translation of potyvirus RNA in a rabbit reticulocyte lysate: Cell-free
      translation strategy and a genetic map of the potyviral genome.
AB  - The translations of tobacco etch virus (TEV) RNA and pepper mottle virus (PeMV)
      in a rabbit reticulocyte lysate were analyzed to determine the effect of RNA
      quality on template activity and to identify all the products of the potyviral
      genome. The size distribution of the in vitro translation products, as analyzed
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was
      dependent on RNA quality. Full-length RNA stimulated the cell-free synthesis
      primarily of a 87,000 (87K) molecular weight product for TEV and a 78K product
      for PeMV. RNA with limited fragmentation stimulated a number of discrete
      products, while highly fragmented RNA did not act as a template. RNA
      monocistronic for capsid protein was not detected. Four of the six discrete
      translation products were identified by reactivity with antisera to four virus
      specific proteins. A number of other products, which were consistently
      immunoprecipitated with more than one antiserum, were detected. Products were
      presumed to be premature terminations and/or gene readthroughs on the basis of
      serological reactions and of molecular weight estimates. These readthroughs were
      useful in linking genes and in constructing a genetic map of the potyviral
      genome. The proposed genetic map for TEV is as follows: 5' end-87K protein gene
      49K nuclear inclusion protein gene-50K protein gene-70K cylindrical inclusion
      protein gene-54K nuclear inclusion protein gene-30K capsid protein gene-3' end.
      The proposed genetic map for PeMV is as follows: 5' end-78K protein gene-49K
      protein gene-41K protein gene-68K cylindrical inclusion protein gene-56K protein
      gene-33K capsid protein gene-3' end. The proposed genetic map accounts for 95% of
      the estimated coding capacity of the TEV RNA and 93% of the PeMV RNA.

PMID- 18631663
TI  - Structural polypeptides of Choristoneura biennis entomopoxvirus.
AB  - The structural polypeptides of Choristoneura biennis (Free) entomopoxvirus (EPV)
      were analyzed. The virion contained at least 40 polypeptides ranging from 12,000
      to 250,000 in molecular weight. Twelve major proteins constitute 95% of the total
      virus protein. Core particles generated by treatment with Nonidet P-40, under
      conditions during which endogenous alkaline protease is active, display a smooth
      exterior similar to those obtained for orthopoxviruses. The major component of
      these cores is a polypeptide with a molecular weight of 59,000.

PMID- 18631664
TI  - Cucumber mosaic virus and peanut stunt virus differ in an initial event that
      occurs during the infection of cowpea leaf epidermal cells.
AB  - Using procedures described earlier for peanut stunt virus (PSV) (G. I. Mink,
      Virology 72, 291-298, 1976), hydroxylamine, ribonuclease (RNase), and tetrachloro
      o-benzoquinone were used to determine 10-min inactivation profiles for cucumber
      mosaic virus (CMV) and CMV-RNA. These profiles indicate that the first event that
      is detectable by the use of inactivating agents in the infection of Cowpea
      primary leaves by either CMV or CMV-RNA differed significantly from that reported
      earlier for PSV and PSV-RNA. The results suggested that a fraction of the intact
      CMV applied to Cowpea leaves was somehow protected from the effects of
      inactivating agents immediately upon inoculation. This phenomenon was eliminated
      by neutralizing the strong negative surface charge of CMV with cytochrome c.
      During the first 10-min interval after inoculation CMV and CMV-RNA appear to be
      attached to some stationary cell component. The results indicate that Cowpea
      epidermal cells can distinguish almost instantly between CMV and PSV or between
      their respective RNAs.

PMID- 18631665
TI  - Infection of chlorophyll-less protoplasts from etiolated Chinese cabbage
      hypocotyls by turnip yellow mosaic virus.
AB  - Protoplasts were prepared from hypocotyls of dark-grown, 8-day-old Chinese
      cabbage seedlings. Pectinase and cellulase were used together in a one-step
      procedure. These hypocotyl protoplasts did not contain detectable amounts of
      chlorophyll. They could be infected in vitro with turnip yellow mosaic virus
      (TYMV). Virus replication was demonstrated by direct immunofluorescence, enzyme
      linked immunosorbent assay, virus recovery by sucrose density gradient
      centrifugation, and infectivity tests on chinese cabbage plants. The chlorophyll
      less hypocotyl protoplasts supported TYMV replication in the dark as well as in
      the light, while chlorophyll-containing leaf protoplasts allowed TYMV
      multiplication only in the light.

PMID- 18631666
TI  - Sequence of the 3' untranslated region of brome mosaic virus coat protein
      messenger RNA.
AB  - The 3' terminal 337 bases of BMV (brome mosaic virus) coat protein mRNA (BMV
      RNA4) are presented. This sequence includes the terminal portion of the coat
      protein cistron and the complete 300-base 3' noncoding sequence. The 3' noncoding
      sequence displays significant complementarity to the 5' terminal sequence of BMV
      RNA3 but not to the 5' terminal sequence of BMV RNA4.

PMID- 18631667
TI  - TYMV RNA replication in vivo: replicative intermediate is mainly single stranded.
AB  - We have used an in vitro labeled, membrane-bound ds[3H]RNA (C. Mouches, C. Bove,
      and J. M. Bove, 1974, Virology 58, 409-423) to develop a technique by which dsRNA
      can be detected on glycol methacrylate-embedded ultrathin sections by its
      resistance to RNase digestion at high but not at low ionic strength. The RNase
      resistant ds[3H]RNA is detected on the sections by high-resolution
      autoradiography. The technique requires that prior to RNase digestion the
      ultrathin sections be first submitted to a Pronase step. This is accomplished by
      floating the sections on Pronase (1 mg/ml) for 15 min at 30 degrees , washing the
      sections three times, and digesting with RNase at high ionic strength for 90 min
      at 30 degrees . When the washing steps and the RNase hydrolysis are carried out
      at low ionic strength, dsRNA is completely hydrolyzed. We have applied the
      Pronase-RNase technique to investigate whether TYMV-specific dsRNA exists in situ
      after in vivo labeling of the RNAs. [3H]Uridine was fed for 1, 3, and 6 hr
      through the petiole of healthy or TYMV-infected leaves in the presence or absence
      of actinomycin D. For a given treatment aliquots of the same leaves were used for
      three parallel experiments: (1) Araldite embedding for autoradiography; (2)
      glycol methacrylate embedding for enzyme digestion and autoradiography; and (3)
      RNA extraction and analysis by polyacrylamide gel electrophoresis. These
      experiments have shown that after a [3H]uridine absorption by TYMV-infected
      leaves for 1 hr, in the presence of actinomycin D:dsRNA was the main labeled RNA
      species seen on the gels; Araldite-embedded sections were labeled specifically at
      the chloroplast periphery, while glycol methacrylate-embedded sections, submitted
      to the Pronase-RNase technique to detect dsRNA, were found to contain no dsRNA.
      Thus replicative intermediate RNA in TYMV-infected cells is essentially single
      stranded in vivo, and dsRNA is an artifact generated during the RNA extraction
      procedure.

PMID- 18631668
TI  - Activation of the genome of alfalfa mosaic virus is enhanced by the presence of
      the coat protein on all three genome parts.
AB  - The same amount of coat protein stimulates the infectivity of alfalfa mosaic
      virus RNA more when added to the three genome RNAs at once than when preincubated
      with one or two genome RNAs separately before the inoculum is completed. This
      suggests that the coat protein activates the genome by interacting with all three
      parts of it. It could not be demonstrated that infectivity is absolutely
      dependent on this multiple activation because of the possible exchange of protein
      between RNA molecules in the inoculum. However, factors that are likely to
      influence this exchange also have an effect on infectivity. Experiments showed
      that complex formation of coat protein with only the smallest genome RNA (that
      contains the coat protein gene) does not enhance infectivity as compared with
      other individual RNAs and protein combinations. Apparently the expression of the
      coat protein gene is not stimulated in this manner.

PMID- 18631669
TI  - Messenger RNA for the coat protein of southern bean mosaic virus.
AB  - When RNA from southern bean mosaic virus is fractionated on a sucrose gradient,
      the resulting absorbance profile shows a major peak corresponding to 1.4 x 10(6)
      MW together with a considerable amount of slower sedimenting material. The RNA
      from these gradient fractions was translated in wheat embryo extracts and
      reticulocyte lysates. Only RNA in the molecular weight range 0.3 - 0.4 x 10(6)
      was found to induce synthesis of coat protein (designated P3). RNA of molecular
      weight 1.4 x 10(6) induced synthesis of three proteins, P1, P2, and P4.

PMID- 18631670
TI  - Restriction enzyme analysis of the genomes of Plodia interpunctella and Pieris
      rapae granulosis viruses.
AB  - The DNAs from the granulosis viruses of Plodia interpunctella and Pieris rapae
      were clearly distinguishable based on restriction endonuclease fragment patterns.
      By sizing single- and double-digestion products approximate molecular weights of
      72 x 10(2) and 75 x 10(6), respectively, were estimated for the viral genomes.

PMID- 18631672
TI  - Synthesis and characterization of DNA complementary to carnation mottle virus
      RNA.
AB  - DNA complementary to carnation mottle virus-RNA (CarMV RNA) was synthesized using
      the reverse transcriptase of avian myeloblastosis virus (AMV) as enzyme, and an
      hydrolysate of calf thymus DNA as primer. After purification steps that included
      self-annealing and hydroxyapatite chromatography, the DNA transcript was more
      than 99% sensitive to S1 nuclease and hybridized to at least 92% of the CarMV-RNA
      sequences, but not to heterologous RNA. Therefore, the purified transcript was
      single stranded and represented almost all CarMV-RNA sequences. The cDNA
      consisted of small pieces that hybridized to CarMV-RNA with a sharp transition
      corresponding to Crt(1/2) of 2.3 x 10(2) M sec liter(-1). This value is
      consistent with the complexity expected for CarMV-RNA if there is only one kind
      of virion RNA. CarMV-cDNA hybridized completely to a crude RNA preparation from
      CarMV-infected carnation leaves, but not to a comparable RNA preparation from
      healthy leaves, thus permitting the use of CarMV-cDNA to detect and to quantify
      the viral nucleotide sequences in total nucleic acid preparations from fragments
      of carnation cuttings.

PMID- 18631673
TI  - Purification and partial characterization of a bacilliform virus from Agaricus
      bisporus: a single-stranded RNA mycovirus.
AB  - A bacilliform virus from the cultivated mushroom, Agaricus bisporus, has been
      extensively purified and shown to be a unique mycovirus in that the genome is
      single-stranded (ss) RNA. The purification procedure entailed extraction at pH 6,
      followed by polyethylene glycol-NaCl precipitation, and differential, rate-zonal,
      and equilibrium centrifugation. Mushroom bacilliform virus (MBV) has a buoyant
      density of 1.317 g/cm(3) in Cs2SO4, A260/A280 nm absorbance ratio of 1.67, and
      contains approximately 20% nucleic acid by weight. SDS-polyacrylamide gel
      electrophoretic analyses revealed that MBV contains a single major nucleic acid
      species with a molecular weight of 1.4 x 108 and a single capsid polypeptide of
      molecular weight 24,400. The nucleic acid was hydrolyzed by pancreatic
      ribonuclease A in high ionic strength buffer and by 0.4 M KOH, but not by
      pancreatic deoxyribonuclease I. Further, the kinetics of melting of MBV RNA upon
      thermal denaturation closely paralleled that of the ssRNA of tobacco mosaic
      virus. Based on this evidence, we propose that MBV is the first mycovirus shown
      to possess a ssRNA genome.

PMID- 18631674
TI  - The effects of heterologous and homologous coat protein on alkaline disassembly
      of tobacco and tomato isolates of tobacco mosaic virus.
AB  - Tobacco (Tb) and tomato (Tm) isolates of tobacco mosaic virus (TMV) disassemble
      in dilute alkaline solutions (pH > 8.0). Tm-TMV is more sensitive to alkali than
      is Tb-TMV. Tb protein is, however, able to partially stabilize both Tm-TMV and Tb
      TMV, thus retarding the rate of alkaline disassembly. Tm protein is unable to
      stabilize Tm-TMV and also increases the rate of alkaline disassembly of Tb-TMV.

PMID- 18631675
TI  - Reactivity of antisera to endogenous tumor virus for splenic B lymphocytes of
      immunized 15I(5) x 7(2) and 15I(5) x 7(1) chickens.
AB  - Immunofluorescence was employed to assay the spleens from several strains of
      chicken for the presence of antigen reactive with rabbit antisera elicited to the
      endogenous oncornavirus RAV-O. Antigen was detected in numerous islands or
      clusters of B lymphocytes that were localized to splenic red pulp of 15I(5) x
      7(2) and 15I(5) x 7(1) chickens that had been sensitized to sheep red blood
      cells. Competition experiments provided evidence for cross-reactivity with
      structural antigen of RAV-0. Islands of antigen-positive cells were not detected
      in the spleens of nonsensitized 15I(5) x 7(2) or 15I(5) x 7(1) chickens although
      several of these spleens exhibited small numbers of scattered antigen-positive B
      cells. Spleens of sensitized or nonsensitized Spafas MR53 chickens did not react
      to detectable levels with the anti-RAV-O sera.

PMID- 18631676
TI  - Isolation and replication of an occlusion body-deficient mutant of the Autographa
      californica nuclear polyhedrosis virus.
AB  - A spontaneous mutant of the Autographa californica nuclear polyhedrosis virus
      which was deficient in viral occlusion body formation was studied in Trichoplusia
      ni tissue culture cells. Virus multiplication could be divided into four phases
      based on growth curves and the sequential appearance of 25 viral-induced proteins
      identified by pulse labeling and polyacrylamide gel electrophoresis. During the
      latent phase, five viral-induced proteins with molecular weights of 68, 47, 35,
      and 30 thousand (K) were detected. The synthesis of 17 additional viral-induced
      proteins with molecular weights ranging from 64 to 14K was detected during the
      nonoccluded virus (NOV) phase, 10 to 16 hr postinoculation (pi). During the
      transition from NOV to occluded virus formation, 16 to 34 hr pi, the synthesis of
      occlusion body matrix protein (33K) and two additional proteins (15.6 and 13K)
      was detected. During the occlusion phase of replication, after 34 hr pi, NOV
      synthesis ceased; however, the synthesis of the 25 viral-induced proteins
      continued. Posttranslational cleavage was not detected in pulse-chase
      experiments. The occlusion body-deficient mutant induced lower levels of
      occlusion body matrix protein synthesis than the wild type virus. The decrease in
      amount of occluded virions was accompanied by a corresponding increase in the
      number of NOV particles produced.

PMID- 18631677
TI  - Genes of coliphage T1 whose products promote general recombination.
AB  - The RecE bacterial recombination pathway, expressed in strains carrying a sbcA
      mutation, can substitute for the function of gene 4 of phage T1. RecE will also
      substitute for the function of a newly discovered phage gene, 3.5. Like mutants
      in gene 4, gene 3.5 mutants have a DA (DNA synthesis arrest) phenotype under
      nonpermissive conditions. In addition to their effects on DNA synthesis,
      mutations in genes 3.5 and 4 profoundly depress recombination in T1. Inhibition
      of DNA synthesis by nalidixic acid does not effect the frequency of recombinants
      among the small population of progeny phage that are produced. Isolation of T1
      mutants dependent on the RecE function has yielded additional mutants
      specifically in genes 3.5 and 4. Together, these results are interpreted to mean
      that these two phage genes encode components of a general recombination system,
      referred to as T1 Grn. During replication of T1 in conventional hosts the
      essential function of this system is to provide for the formation, via
      recombination, of concatameric DNA molecules, which are the substrates for the
      packaging of DNA into T1 heads.

PMID- 18631678
TI  - Ultrastructure of potato leaf phloem infected with potato leafroll virus.
AB  - Electron microscopy of Russet Burbank potato (Solanum tuberosum L.) leaf midveins
      infected with the potato leafroll virus (PLRV) revealed the pathological effects
      induced by the virus in the phloem. Virus particles were observed in mature sieve
      elements, companion cells, and plasmodesmata connecting the two kinds of cells.
      An early indication of virally induced cellular disturbance in companion cells
      was dilation of mitochondrial cristae followed closely by the appearance of
      vesicles in the parietal cytoplasm. One type of vesicle contained fibrils
      suggestive of nucleic acids and the second type carried an electron opaque
      material. Both types of vesicles were surrounded by two membranes. Rough
      endoplasmic reticulum (ER) formed the outer membrane. Both vesicle types fused
      with the nuclear envelope and were taken up into the nucleus. PLRV particles
      appeared mainly in the cytoplasm, where they were either scattered or localized
      along the membranes of mitochondria, chloroplasts, and vacuoles. In some cells,
      groups of particles were enclosed in the vacuole. The relation of virus particles
      to the nucleus remains problematic: there was no evidence that uptake of vesicles
      into the nucleus resulted in the formation of particles in this organelle. Cells
      in which particles formed became degenerated. Mitochondria swelled and cristae
      separated from the envelope and clumped. Most organelles including the nucleus,
      ribosomes, rough ER, and chloroplasts broke down leaving a fibrillar material
      interspersed with virus particles.

PMID- 18631679
TI  - Relation of the structure of cytoplasmic polyhedrosis virus and the synthesis of
      its messenger RNA.
AB  - Cytoplasmic polyhedrosis virus (CPV) was observed under an electron microscope
      using a combination of staining and shadowing methods. Projections, not only in
      positions horizontal to the grid but also vertical, were clearly visualized. When
      the particle was mildly disrupted with EDTA, genome dsRNA was released from a
      projection. If the particle was previously fixed with glutaraldehyde and then
      disrupted, dsRNA was released with a protein particle, which seemed to correspond
      to the base part of the projection. The protein particle was in most cases at the
      end of the strand, which sometimes takes a supercoiled structure. When CPV was
      incubated during mRNA synthesis, the protein particles appeared in various
      positions along the strands, and loop formations of dsRNA appeared. From these
      observations, we suggest that transcription in this virus particle proceeds as
      follows: genome dsRNA is transcribed by passing through the base part of the
      projection, where the enzymes for mRNA synthesis are located. A completed mRNA is
      released from the virion at the projection.

PMID- 18631680
TI  - Double infection of tobacco protoplasts with brome mosaic virus and cowpea
      chlorotic mottle virus.
AB  - Mixed infections of tobacco protoplasts with Cowpea chlorotic mottle virus (CCMV)
      and brome mosaic virus (BMV) have been studied. Fluorescent antibody staining
      showed that capsids of both viruses were made in doubly infected protoplasts but
      only infectious BMV could be recovered, i.e., BMV dominated in mixed infections
      and prevented synthesis of infectious CCMV. Healthy protoplasts could be infected
      after several hours in culture but the susceptibility to infection decreased with
      time in culture; the decrease was much faster with BMV than with CCMV, probably
      because the difference in electrical charge of the two viruses affects the method
      of entry into the protoplasts. If inoculation with the second virus was delayed
      there was an increasing resistance to superinfection (interference or cross
      protection) so that when the delay between inoculations was more than 8 hr BMV
      was no longer able to infect protoplasts previously infected with CCMV and vice
      versa. No recombinants between BMV and CCMV were observed. Attempts to rescue a
      temperature-sensitive strain of CCMV with BMV under restrictive conditions (35
      degrees ) were unsuccessful; dominance by BMV prevented synthesis of infectious
      CCMV RNA.

PMID- 18631681
TI  - Polypeptides associated with inclusion bodies from leaves of turnip infected with
      cauliflower mosaic virus.
AB  - Inclusion bodies, the major intracellular site of accumulation of cauliflower
      mosaic virus (CaMV), have been partially purified by centrifugation onto a
      saturated sucrose cushion, followed by detergent treatment to lyse chloroplasts,
      then centrifugation on a saturated sucrose cushion again. The resulting
      preparation was enriched for inclusion bodies as judged by light and electron
      microscopic observation and by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of the polypeptides in the preparation. Two major polypeptides of
      61,000 and 43,000 apparent molecular weights were found in inclusion body
      preparations from leaves infected separately with each of three different
      isolates of CaMV. Polypeptides of apparent molecular weights 56,000, 50,000,
      39,000, 37,000, and 34,000 were also detected in preparations from infected
      leaves, but not in comparable preparations from healthy leaves. The mobilities of
      all but the 61,000 and 34,000 molecular weight polypeptides were slightly
      different from the CM4-184 isolate, as compared with Cabbage B Davis or NY8153.
      The 61,000 molecular weight polypeptide did not correspond in mobility to any of
      the virion polypeptides. The relative intensities of polypeptide bands common to
      inclusion bodies and isolated virions were different in these two preparations,
      suggesting that considerable degradation took place during virion isolation.

PMID- 18631682
TI  - Relationships between brain and mind. Preface.

PMID- 18631683
TI  - Neuropsychology and behavior. Foreword.

PMID- 18631684
TI  - Cholinergic components of frontal lobe function and dysfunction.

PMID- 18631685
TI  - Neurochemistry of cognition: serotonergic and adrenergic mechanisms.

PMID- 18631686
TI  - Cortical neuroanatomy and cognition.

PMID- 18631687
TI  - Functional neuroimaging of cognition.

PMID- 18631688
TI  - Neuropsychology of aging and dementia.

PMID- 18631689
TI  - Neuropsychological testing: bedside approaches.

PMID- 18631691
TI  - Retrograde memory loss.

PMID- 18631690
TI  - Anterograde amnesia.

PMID- 18631692
TI  - Disorders of semantic memory.

PMID- 18631693
TI  - Implicit learning and memory.

PMID- 18631694
TI  - Working memory.

PMID- 18631695
TI  - The dysexecutive syndromes.

PMID- 18631696
TI  - Apraxia of speech.

PMID- 18631697
TI  - Aphasia.

PMID- 18631698
TI  - Cognitive processes underlying reading and writing and their neural substrates.

PMID- 18631699
TI  - Apraxia.

PMID- 18631700
TI  - Acalculia.

PMID- 18631701
TI  - Hemispatial neglect.

PMID- 18631702
TI  - Visuospatial and visuoconstructive deficits.

PMID- 18631703
TI  - Optic ataxia and Balint's syndrome: neuropsychological and neurophysiological
      prospects.

PMID- 18631704
TI  - Chapter 21 Visual agnosia.

PMID- 18631705
TI  - Illusory reduplications of the human body and self.

PMID- 18631706
TI  - The musical brain.

PMID- 18631707
TI  - Visual art and the brain.

PMID- 18631708
TI  - Chapter 25 Laboratory testing of emotion and frontal cortex.

PMID- 18631709
TI  - Neuropsychological characterization of mild cognitive impairment.

PMID- 18631710
TI  - Neuropsychology of Alzheimer's disease.

PMID- 18631711
TI  - Neuropsychology of frontotemporal dementia.

PMID- 18631712
TI  - Neuropsychology of dementia with Lewy bodies.

PMID- 18631713
TI  - The neuropsychology of vascular dementia.

PMID- 18631714
TI  - Limited sequence variation in the leader sequence of RNA 4 from several strains
      of alfalfa mosaic virus.
AB  - The sequences of the 5'-noncoding regions of RNA 4 of seven strains of alfalfa
      mosaic virus were compared. In each case, the coat protein cistron was preceded
      by a leader sequence of 39 nucleotides (including the initiator codon). At
      position 26, an A-, G-, or U-residue was found. Otherwise the leader sequences
      are identical.

PMID- 18631715
TI  - Cytochemical characterization of plastidal inclusions in Abutilon mosaic-infected
      Malva parviflora mesophyll cells.
AB  - Electron microscopy of plastids from mesophyll cells of Malva parviflora infected
      with the Abutilon mosaic virus revealed elongated "chains of pearls" with
      subunits of 7.5 nm in diameter. Paracrystalline inclusions of the chains of
      pearls studied by means of cytochemical techniques gave evidence of the presence
      of DNA.

PMID- 18631716
TI  - A procedure for rapid isolation and analysis of cauliflower mosaic virus DNA.
AB  - A simple and rapid procedure has been developed for the small-scale isolation of
      crude preparations of cauliflower mosaic virus DNA. The preparations are
      relatively free of contaminating cellular DNA and are sufficiently pure to be
      digested with restriction enzymes. The method enables plants infected with single
      lesion isolates of mutagenized viral DNA to be rapidly screened for particular
      restriction endonuclease sites.

PMID- 18631717
TI  - The composition of bean golden mosaic virus and its single-stranded DNA genome.
AB  - Bean golden mosaic virus (BGMV) contains predominantly circular single-stranded
      DNA, but DNA isolation by treating virus with proteinase K results in conversion
      of the DNA to a linear form. The conversion is inhibited by as little as 0.025%
      sodium dodecyl sulfate but not by phenylmethylsulfonyl fluoride and does not
      occur when purified DNA is incubated with proteinase K. Protein is not involved
      in the covalent structure of BGMV DNA; the conversion appears to be caused by an
      endonuclease that copurifies with the virus and is resistant to proteinase K.
      BGMV contains a major capsid protein with an estimated molecular weight of
      27,400. Two minor proteins are found, even in the most highly purified virus
      preparations; their origin and role in virus structure or function are unknown.
      BGMV particles contain 19% DNA; therefore each geminate particle must contain a
      single DNA molecule, of which over 90% are circular. The estimated molecular
      weight of the virus is 3.8 x 10(6).

PMID- 18631718
TI  - The housefly virus contains double-stranded RNA.
AB  - The housefly virus (HFV) was shown to contain double-stranded RNA (dsRNA) when
      examined by fluorescent staining with acridine orange (AO). The pale green color
      observed was not affected by digestion with single-stranded specific nuclease. In
      contrast, denatured wet, but not dried virus samples fluoresced red. Viral RNA,
      extracted and analyzed by polyacrylamide gel electrophoresis, was resolved into
      10 segments, which were not affected by predigestion with RNase, confirming the
      ds nature of the genome. The HFV thus belongs to the family Reoviridae. By
      comparison with dsRNA segments from reovirus type 3, Dearing strain, the housefly
      virus genome is estimated to have a molecular weight of 17 to 18 x 10(6) daltons.

PMID- 18631719
TI  - In vitro translation of tobacco etch virus RNA.
AB  - The wheat-embryo-derived cell-free system was optimized for translation of
      tobacco etch virus (TEV) RNA. When examined by polyacrylamide gel
      electrophoresis, the product of the TEV RNA stimulated system proved to be a
      single protein with a molecular weight of 40,000. This finding is different from
      results obtained when TEV RNA is used as a template in the rabbit reticulocyte
      lysate in vitro protein-synthesizing system.

PMID- 18631720
TI  - The genome-linked protein of cowpea mosaic virus is coded by RNA from the bottom
      component.
AB  - It has recently been shown that RNA from the bottom component of cowpea mosaic
      virus is capable of self-replication in cowpea mesophyll protoplasts, providing a
      tool for the investigation of the contribution of each RNA strand toward viral
      multiplication. Evidence is presented here, using this system, to show that the
      genome-linked protein is coded by the RNA from the bottom component. As the
      replicase function is coded by this RNA, the results remain consistent with the
      involvement of the genome-linked protein in viral RNA replication.

PMID- 18631721
TI  - Cell-free translation of tobacco vein mottling virus RNA.
AB  - Tobacco vein mottling virus (TVMV), a member of the potyvirus group, was
      translated in a rabbit reticulocyte cell-free system. The RNA was approximately
      5% as active as rabbit globin mRNA in directing protein synthesis. Translation
      was stimulated approximately 15% by the cap analog pppm7G, a phenomenon which has
      also been observed with uncapped viral RNAs. Treatment with NaIO4 and NaB(3H]4
      under conditions which label the caps of globin and ovalbumin mRNA failed to
      produce labeled cap structures in TVMV RNA. Approximately 20 polypeptides,
      ranging from 20,000 to 100,000 daltons, were produced in the reticulocyte system
      programmed with TVMV RNA. The predominant species (P75) had a molecular weight of
      75,000. The same major polypeptides were produced in the wheat germ system, but
      there was relatively greater synthesis of the smaller polypeptides. Incubation of
      the reticulocyte system in the presence of cycloheximide following an initial
      period of synthesis failed to cause breakdown of larger polypeptides into smaller
      polypeptides. Preincubation of TVMV RNA with the reticulocyte system before
      addition of labeled amino acids caused greater synthesis of the smaller
      polypeptides, suggesting that they are derived from fragments of the RNA produced
      during the incubation. Translation of TVMV RNA which had been bound to oligo(dT)
      cellulose yielded nearly the same spectrum of polypeptides, but synthesis of
      polypeptides smaller than 52,000 daltons was reduced. At low ionic strength, only
      polypeptides of 52,000 daltons and smaller were synthesized. At high ionic
      strength, P75 was essentially the only product synthesized. Antibody to whole
      virus precipitated many of the polypeptides, including P75, suggesting that they
      contain the coat protein sequence. No polypeptide with the electrophoretic
      mobility of authentic coat protein, however, was precipitated. Comparison of
      partial proteolytic digests of P75 and authentic coat protein provided further
      evidence for sequence homology.

PMID- 18631722
TI  - Three-dimensional structure of pinwheel inclusions as determined by analytic
      geometry.
AB  - The three-dimensional ultrastructure of pinwheel inclusions found in two plant
      virus-host systems was determined by computer-assisted analytic geometry. Data
      obtained from electron micrographs of serially sectioned pinwheel inclusions were
      used to generate mathematical equations. The three-dimensional models described
      by the equations indicated that some pinwheels assume the hourglass shapes of
      elliptic hyperboloids. Electron micrographs obtained from thick sections of
      pinwheel inclusions tilted at various angles supported the elliptic hyperboloid
      models described by the mathematical equations.

PMID- 18631723
TI  - Similar sequences from the 5' end of cowpea mosaic virus RNAs.
AB  - Similar, large (N approximately 40) oligonucleotides are released from each of
      the two cowpea mosaic virus genomic RNAs by digestion with ribonuclease T1. Each
      large oligonucleotide was radiolabeled at the 3' end, and the nucleotide sequence
      was determined by base-specific partial degradation and analysis of the
      fragments. Specific deoxyoligonucleotides that are complementary to a portion of
      each large oligonucleotide were primers in reverse transcription reactions with
      intact virion RNA as template. Sequences to the 5' side of the large
      oligonucleotide sequences, and extending almost to the 5' end of each RNA, were
      read from analyses of transcripts that had been terminated by the incorporation
      of 2',3'-dideoxynucleoside-5'-phosphate residues. We report sequences of 87 and
      79 nucleotide residues, respectively, from the two virus RNAs. The two sequences
      show many similarities and can be folded into a similar pattern to accommodate
      base pairing.

PMID- 18631724
TI  - Detection of a wide spectrum of tobacco mosaic virus strains by indirect enzyme
      linked immunosorbent assays (ELISA).
AB  - The suitability of two ELISA procedures for detecting different strains of
      tobacco mosaic virus (TMV) by means of a single labeled antibody preparation has
      been determined. The specificity of the double-antibody sandwich method of ELISA
      was so great that enzyme conjugates prepared with antibodies to one strain did
      not react with closely related strains. The indirect method of ELISA which uses
      an antiglobulin enzyme conjugate was capable of detecting a wide range of TMV
      strains with antiserum to one strain only. The indirect procedure is thus better
      suited for diagnostic work. Both methods of ELISA were able to detect
      relationships between the coat proteins of different TMV strains. These results
      confirm that the dissociated subunits of different strains are more closely
      related than the corresponding intact virions.

PMID- 18631725
TI  - "Softening of the brain." Preface.

PMID- 18631726
TI  - The dementias. Foreword.

PMID- 18631727
TI  - History of dementia.

PMID- 18631728
TI  - Neuropsychological examination in dementia.

PMID- 18631729
TI  - Executive dysfunction and neuropsychological testing.

PMID- 18631730
TI  - Neuropsychiatric evaluation in dementia.

PMID- 18631731
TI  - Electrophysiological evaluation of dementia.

PMID- 18631732
TI  - Feature extraction and strategy of analyzing structural neuroimaging in dementia.

PMID- 18631733
TI  - Strategies for using molecular neuroimaging in dementia.

PMID- 18631734
TI  - Quality of life in dementias.

PMID- 18631735
TI  - Diagnosis and management of caregiver burden in dementia.

PMID- 18631736
TI  - The memory disorders clinic.

PMID- 18631737
TI  - Legal aspects of dementia.

PMID- 18631738
TI  - Ethical issues in the care of the patient with dementia.

PMID- 18631739
TI  - Economical aspects of dementia.

PMID- 18631740
TI  - Neuropathologic classification of dementias: introduction.

PMID- 18631741
TI  - Tau, a biological marker of neurodegenerative diseases.

PMID- 18631742
TI  - Biologic models of neurodegenerative disorders.

PMID- 18631743
TI  - The relationship between nosology, etiology and pathogenesis in neurodegenerative
      diseases.

PMID- 18631744
TI  - Alzheimer's disease: epidemiology.

PMID- 18631745
TI  - Clinical symptoms in Alzheimer's disease.

PMID- 18631746
TI  - Mild cognitive impairment.

PMID- 18631747
TI  - The genetics of Alzheimer's disease.

PMID- 18631748
TI  - Neuropathology of Alzheimer's disease.

PMID- 18631749
TI  - Biochemistry and molecular biology of amyloid beta-protein and the mechanism of
      Alzheimer's disease.

PMID- 18631750
TI  - Biological CSF markers of Alzheimer's disease.

PMID- 18631751
TI  - Symptomatic therapeutic aspects in Alzheimer's disease.

PMID- 18631752
TI  - Perspectives of Alzheimer's disease treatments.

PMID- 18631754
TI  - Clinical aspects of Parkinson dementia.

PMID- 18631753
TI  - Biological transgenic mouse models of Alzheimer's disease.

PMID- 18631755
TI  - Clinical aspects of dementia with Lewy bodies.

PMID- 18631756
TI  - The genetics and molecular biology of alpha-synuclein.

PMID- 18631757
TI  - Neuropathology of dementia with Lewy bodies.

PMID- 18631758
TI  - Epidemiological aspects of frontotemporal dementia.

PMID- 18631759
TI  - Frontotemporal lobar degeneration: clinical and pathologic overview.

PMID- 18631760
TI  - Clinical aspects of hereditary frontotemporal dementia.

PMID- 18631761
TI  - Clinical aspects of TDP-43 proteinopathy, neurofilament inclusion body disease
      and dementias lacking distinctive proteinopathy.

PMID- 18631762
TI  - The genetics of frontotemporal dementia.

PMID- 18631763
TI  - Neuropathology of hereditary forms of frontotemporal dementia and parkinsonism.

PMID- 18631764
TI  - Neuropathology of Pick body disease.

PMID- 18631765
TI  - Dementia and motor neuron disease.

PMID- 18631766
TI  - Neuronal intermediate filament inclusion disease.

PMID- 18631767
TI  - Biological models in frontotemporal dementias.

PMID- 18631768
TI  - The epidemiology of progressive supranuclear palsy.

PMID- 18631769
TI  - Clinical aspects of progressive supranuclear palsy.

PMID- 18631770
TI  - Genetics of progressive supranuclear palsy.

PMID- 18631771
TI  - Neuropathology of progressive supranuclear palsy.

PMID- 18631772
TI  - Current and future therapeutic approaches in progressive supranuclear palsy.

PMID- 18631773
TI  - Corticobasal degeneration: clinical aspects.

PMID- 18631774
TI  - Neuropathology and genetics of corticobasal degeneration.

PMID- 18631776
TI  - Clinical aspects of dementia with argyrophilic grains.

PMID- 18631775
TI  - Current and future management of the corticobasal syndrome and corticobasal
      degeneration.

PMID- 18631777
TI  - Argyrophilic grain disease.

PMID- 18631778
TI  - Clinical aspects of hippocampal sclerosis.

PMID- 18631779
TI  - Neuropathology of hippocampal sclerosis.

PMID- 18631780
TI  - Primary progressive aphasia and kindred disorders.

PMID- 18631782
TI  - Neuropathology of Huntington's disease.

PMID- 18631781
TI  - "Pre-symptomatic" Huntington's disease.

PMID- 18631783
TI  - The biology of Huntington's disease.

PMID- 18631784
TI  - Therapeutic approach in Huntington's disease.

PMID- 18631785
TI  - The Epidemiology of vascular dementia.

PMID- 18631786
TI  - Clinical and therapeutic aspects of vascular dementia.

PMID- 18631787
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy.

PMID- 18631788
TI  - The neuropathology of vascular and mixed dementia and vascular cognitive
      impairment.

PMID- 18631789
TI  - Understanding and managing cognitive dysfunction in multiple sclerosis.

PMID- 18631790
TI  - Neuropathology of cognitive dysfunction in multiple sclerosis.

PMID- 18631791
TI  - Leukodystrophies: clinical and therapeutic aspects.

PMID- 18631792
TI  - Clinical and therapeutic aspects of prion disease.

PMID- 18631793
TI  - Clinical aspects of variant Creutzfeldt-Jakob disease.

PMID- 18631794
TI  - Biology and neuropathology of prion diseases.

PMID- 18631795
TI  - Human immunodeficiency virus-associated dementia: clinical aspects, biology, and
      treatment.

PMID- 18631796
TI  - Neuropathology and HIV dementia.

PMID- 18631797
TI  - Clinical and therapeutic aspects of dementia in syphilis and Lyme disease.

PMID- 18631798
TI  - Biology and neuropathology of dementia in syphilis and Lyme disease.

PMID- 18631799
TI  - Epidemiology of alcohol-related dementia.

PMID- 18631800
TI  - Toxic dementias.

PMID- 18631801
TI  - Neuropathology of alcohol-related cognitive alterations.

PMID- 18631802
TI  - Paraneoplastic disorders of the memory and cognition: clinical aspects and
      therapeutic approaches.

PMID- 18631803
TI  - Brain tumors and dementia.

PMID- 18631804
TI  - Clinical aspects and biology of normal pressure hydrocephalus.

PMID- 18631805
TI  - Association of type 1 viral-like dsRNA with club-shaped particles in hypovirulent
      strains of Endothia parasitica.
AB  - A hypovirulent strain (H1) of Endothia parasitica. (EP 113) contained enough
      dsRNA, 7 mug/g, to be detected in unconcentrated nucleic acid extracts. Two to
      five (the most common number) major dsRNA components (MW = 4.4-6.2 x 10(6)) were
      detected in different preparations. A distinctive pattern of minor dsRNA
      components (MW < 4.0 x 10(6)) was also detected. Single-stranded RNA (MW = 2.0
      3.1 x 10(6)) was not detected in nucleic acid samples which contained readily
      detectable amounts of dsRNA. Most of the dsRNA was associated with pleiomorphic
      club-shaped particles up to 300 nm long with spherical heads (diameter = 50-90
      nm). The particles were purified from clarified extracts by polyethylene glycol
      precipitation and differential centrifugation. They were resolved as broad bands
      in rate-zonal (S(20,W) = 180 S) and equilibrium (buoyant density = 1.28 g/cm(3)
      in CsCl) density gradient centrifugation and had a nucleoprotein-like absorbance
      profile (260 nm/280 nmn ratio = 1.23-1.28) with unusual absorbance peaks at 260,
      269, 280, and 293 ran. The partially purified preparation also contained large
      membrane-like bodies (buoyant density = 1.23 g/cm(3)). Similarly prepared
      extracts from a virulent strain (V) lacked dsRNA, club-shaped particles, and
      large membrane-like bodies. All these components were also detected in extracts
      of a hypovirulent strain (H2) generated by conversion of the virulent strain with
      strain EP 113. The appearance and properties of the club-shaped particle suggest
      that it is either a new and pleiomorphic type of fungal virus-like particle or a
      site of accumulation of a complex dsRNA.

PMID- 18631806
TI  - Properties of the complementary RNA sequences associated with infection by the
      citrus exocortis viroid.
AB  - The citrus exocortis disease, caused by the low molecular weight viroid RNA, has
      recently been shown to include viroid complementary RNA in nucleic acid extracts.
      Purification procedures indicate the presence of viroid complementary sequences
      in both 2 M LiCl precipitate and 2 M LiCl supernatant fractions. These
      complementary sequences are detected in preparations from both the high and the
      low molecular weight regions of polyacrylamide gels. This population
      heterogeneity coupled with the subcellular distribution indicates viroid-related
      structures which may be involved in the processes of replication and
      pathogenesis.

PMID- 18631807
TI  - Transcription of the cauliflower mosaic virus genome in isolated nuclei from
      turnip leaves.
AB  - Nuclei isolated from turnip (Brassica rapa L. c.v. Just Right) leaves infected
      with cauliflower mosaic virus synthesize RNA in vitro which hybridizes to
      purified cauliflower mosaic virus DNA. Nuclei isolated from uninfected leaves do
      not produce these viral transcripts in vitro. Viral-specific transcription in
      isolated nuclei is catalyzed by endogenous DNA-dependent RNA polymerase 11 based
      on sensitivity to alpha-amanitin and ionic strength optima. Only one strand of
      the viral genome is transcribed in vitro in isolated nuclei. The RNA synthesized
      in vitro hybridizes to the same strand and EcoRI restriction fragments of
      cauliflower mosaic virus DNA as the viral-specific RNA that accumulates in vivo
      in infected turnip leaves.

PMID- 18631808
TI  - A new viral RNA species in tobacco rattle virus-infected tissue.
AB  - Tobacco rattle virus (CAM strain)-infected tissue contains at least one unique
      species of virus-specific RNA in addition to the two virion RNAs. The new species
      (RNA-3; MW 0.5 x 10(6)) was characterized as follows: (1) Its synthesis and
      presence were detected by electrophoresis and fluorographic analysis of an
      extract of infected tissue that had been treated with actinomycin D and exposed
      to [3H]uridine; (2) its genesis from RNA-2 was determined by immobilization on
      specially treated diazotized paper and hybridization to cDNAs prepared to TRV
      RNAs 1 and 2; and (3) its template activity for a 30,000 MW protein was
      determined with the aid of a wheat germ-derived cell-free translation system.

PMID- 18631809
TI  - The polarity of assembly of papaya mosaic virus and tobacco mosaic virus RNAs
      with PMV-protein under conditions of nonspecificity.
AB  - The problem of the rapid multiinitiation of papaya mosaic virus or tobacco mosaic
      virus RNA by PMV-protein near pH 7.0 at low ionic strength has been overcome. If
      NaCl is added to 0.1 M, both RNAs are first encapsidated at their respective 5'
      ends. This shows that the initial site of helix formation depends on the protein
      rather than the RNA.

PMID- 18631810
TI  - Phosphorylated proteins in cauliflower mosaic virus.
AB  - Autoradiography of dodecyl sulfate-impregnated polyacrylamide gels after
      electrophoresis of the proteins from 32P-labeled cauliflower mosaic virus (CaMV)
      showed that two of the structural proteins were phosphorylated. These two
      proteins of 44 and 58 kilodaltons (kd) occur as minor components with some
      strains of the virus, but with other virus strains under particular conditions
      the 44-kd protein appears as a major component of the virion. The site of
      phosphorylation was found to be phosphoserine and phosphothreonine. It is
      suggested from these results that the 58-kd protein may be the primary
      translation product of the coat protein gene of CaMV and that the 44-kd and other
      lower molecular weight forms of the coat protein are derived from this
      polypeptide by proteolysis.

PMID- 18631811
TI  - The effect of limited proteolysis on the antigenic stability of cauliflower
      mosaic virus.
AB  - Serological differences between several isolates of cauliflower mosaic virus
      (CaMV) were shown by double antibody enzyme immunoassays and serum cross
      absorption. Relationships established in this way were not consistent, and as a
      possible reason, the effect of naturally occurring proteolysis of the CaMV capsid
      polypeptide on the serological reactivity of the virus was investigated. Changes
      in serological reactivity due to proteolysis were of a similar magnitude as the
      differences in reactivity between different isolates.

PMID- 18631814
TI  - Consciousness: concepts, neurobiology, terminology of impairments, theoretical
      models and philosophical background.

PMID- 18631815
TI  - Consciousness: its neurological relevance.

PMID- 18631816
TI  - Delirium in the critically ill patient.

PMID- 18631817
TI  - Coma and stupor.

PMID- 18631818
TI  - Herniation.

PMID- 18631819
TI  - The vegetative and minimally conscious states.

PMID- 18631820
TI  - Metabolic encephalopathies.

PMID- 18631821
TI  - Nutritional disorders.

PMID- 18631822
TI  - Coma induced by intoxication.

PMID- 18631823
TI  - Ischemic stroke and anoxic-ischemic encephalopathy.

PMID- 18631824
TI  - Infectious etiologies of altered consciousness.

PMID- 18631825
TI  - Traumatic brain injury.

PMID- 18631826
TI  - Seizures and impairment of consciousness.

PMID- 18631827
TI  - Syncope.

PMID- 18631828
TI  - Altered consciousness associated with brain neoplasms.

PMID- 18631829
TI  - Abnormal conscious state and coma in transplant recipients.

PMID- 18631830
TI  - Pregnancy and coma.

PMID- 18631831
TI  - Psychogenic unresponsiveness and nonepileptic seizures.

PMID- 18631832
TI  - Coma in childhood.

PMID- 18631833
TI  - Management of the comatose patient.

PMID- 18631834
TI  - Ethical issues in the management of patients with impaired consciousness.

PMID- 18631835
TI  - Nucleotide sequence homology of thirteen tobamovirus RNAs as determined by
      hybridization analysis with complementary DNA.
AB  - The extent of RNA sequence homology between 13 isolates of tobamoviruses has been
      estimated by hybridization analysis using radioactive complementary DNA. Hybrid
      formation between complementary [3H]DNA prepared against 7 of the tobamovirus
      RNAs and the RNAs of the 13 isolates was assayed with the single-strand-specific
      S1 nuclease. The presence of mismatched regions in the DNA: RNA hybrids was shown
      by variation of the stringency of the conditions for the hybridization and S1
      nuclease assay. The data obtained have allowed the allocation of the 13 isolates
      into five groups on the basis of significant sequence homology between members of
      each group. Members of two of these groups were further divided into subgroups on
      the basis of differences in the hybridization data. Although hybridization
      analysis using labeled complementary DNA is considered the method of choice at
      present for estimating sequence homology between viral RNAs, the limitations
      inherent in any hybridization approach are discussed.

PMID- 18631836
TI  - Physicochemical properties and location of capsule components, in particular the
      synergistic factor, in the occlusion body of a granulosis virus of the armyworm,
      Pseudaletia unipuncta.
AB  - A synergistic strain of granulosis virus (GVH) enhances the infection of larvae
      of the armyworm, Pseudaletia unipuncta, with a nuclear polyhedrosis virus (NPV).
      The matrix of the capsule (occlusion body) of GVH contains two major components,
      the structural protein and the synergistic factor. The structure of the capsule
      matrix of GVH was analyzed with a primary amine-coupling reagent, 2,4,6,
      trinitrobenzene 1-sulfonic acid (TNBS). When undissolved capsules are incubated
      with TNBS, only the structural protein is labeled by TNBS. This indicates that
      the synergistic factor is not accessible to TNBS. Tests with the isolated capsule
      components show that the synergistic factor is more soluble than the structural
      protein at neutral pH. The synergistic factor has a strong affinity for viral
      envelopes. The attachment of about eight molecules of the synergistic factor to
      each enveloped NPV greatly enhances the infectivity of the virus.

PMID- 18631837
TI  - Preface. Neuromuscular junction disorders.

PMID- 18631839
TI  - The most vulnerable synapse: historic aspects of neuromuscular junction
      disorders.

PMID- 18631840
TI  - Reliability of neuromuscular transmission and how it is maintained.

PMID- 18631841
TI  - The neuromuscular junction.

PMID- 18631842
TI  - Electromyographic aspects of neuromuscular junction disorders.

PMID- 18631843
TI  - The immunopathogenesis of myasthenia gravis.

PMID- 18631844
TI  - Autoantibodies in different forms of myasthenia gravis and in the Lambert-Eaton
      syndrome.

PMID- 18631845
TI  - Clinical features of myasthenia gravis.

PMID- 18631846
TI  - Therapy of myasthenia gravis.

PMID- 18631847
TI  - The Lambert-Eaton myasthenic syndrome.

PMID- 18631848
TI  - Congenital myasthenic syndromes.

PMID- 18631849
TI  - Botulism.

PMID- 18631850
TI  - Chapter 12 Neurotoxicology of neuromuscular transmission.

PMID- 18631851
TI  - Organophosphate and carbamate poisoning.

PMID- 18631852
TI  - Peripheral nerve hyperexcitability and the neuromuscular junction.

PMID- 18631854
TI  - Pharmacogenetics in solid organ transplantation: current status and future
      directions.
AB  - Tailoring of immunosuppressive drug therapy to the specific requirements of the
      individual patient to optimize efficacy and minimize toxicity remains one of the
      biggest challenges in solid organ transplantation. Pharmacogenetic and
      pharmacogenomic research, studying the effects of genetic polymorphisms on drug
      disposition and action, holds promise to produce useful clinical tools for
      individualizing immunosuppressive therapy. In the past years, many interesting
      studies have been reported, assessing the impact of single nucleotide
      polymorphisms of genes encoding drug metabolizing enzymes, drug transporters and
      to lesser extent-pharmacological target molecules, on pharmacokinetics and
      pharmacodynamics of immunosuppressive drugs like tacrolimus, cyclosporine,
      sirolimus, mycophenolic acid, and corticosteroids. Currently, we still are in the
      early phases of this exciting research, and the question whether pharmacogenetic
      profiling will eventually become a useful clinical tool remains to be answered.

PMID- 18631853
TI  - Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial
      fibrosis.
AB  - Chronic allograft tubular atrophy/interstitial fibrosis (TA/IF) is a major cause
      of late allograft loss. A major challenge to the future of kidney transplantation
      is to dissect the identifiable causes of chronic allograft TA/IF and to develop
      cause-specific treatment strategies. Emerging evidence suggests that epithelial
      to-mesenchymal transition (EMT) is an important event in native and transplant
      kidney injury, including chronic allograft TA/IF. During EMT, tubular epithelial
      cells are transformed into myofibroblasts through a stepwise process including
      loss of cell-cell adhesion and E-cadherin expression, de novo alpha-smooth muscle
      actin expression, actin reorganization, tubular basement membrane disruption,
      cell migration, and fibroblast invasion with production of profibrotic molecules
      such as collagen types I and III and fibronectin. We examined in this review the
      molecular and cellular pathways of EMT and their involvement in chronic allograft
      tubulointerstitial fibrosis. We examined the role of alloimmune T cells and
      oxidative stress in this context and evaluated EMT as a marker of disease
      progression. Potential therapeutic options are discussed. In conclusion, there is
      enough evidence demonstrating that EMT is involved in the pathogenesis of chronic
      allograft tubulointerstitial fibrosis. However, the extent of its contribution to
      allograft fibrogenesis remains unknown, and only interventional trials will
      enable us to clarify this question. Furthermore, additional data are required to
      determine whether EMT may be used as a surrogate marker of disease progression in
      kidney transplant recipients.

PMID- 18631855
TI  - Predicting delayed graft function and mortality in kidney transplantation.
AB  - Kidney transplantation (KT) is the treatment of choice for end-stage renal
      failure, but such patients are increasingly older and have additional comorbid
      conditions leading to high mortality rates after transplantation. Delayed graft
      function is a common complication after KT, especially in recipients who receive
      expanded criteria donor, and these complications are associated with a poorer
      graft survival in the long term. Taken together, an appropriate assessment of
      comorbidity grouped in prognostic indexes could be a useful tool to make crucial
      therapeutic decisions at the time of transplant. Allocation systems based upon a
      recipient risk score, as well as identification of risk factors for delayed graft
      function, may improve outcomes after KT. The aim of this review is to assess the
      contribution and utility of comorbid conditions, grouped in prognostic indexes to
      predict and improve kidney transplant outcomes.

PMID- 18631856
TI  - Anti-major histocompatibility complex class I-related chain A antibodies in organ
      transplantation.
AB  - Candidate trigger antigens for alloreactive responses have been appearing
      continuously in the organ transplant scenario. Major histocompatibility complex
      class I-related chain A (MICA) is a polymorphic gene family, located near the HLA
      B locus on chromosome 6, that encode a 62-kd cell surface glycoprotein.
      Endothelial cells, in addition to many cell lines, express MICA, whereas resting
      lymphocytes do not, making this polymorphic molecule a target for both cellular
      and humoral immune responses. Major histocompatibility complex class I-related
      chain A antigens are able to elicit the synthesis of alloantibodies in transplant
      recipients. These antibodies have been found in association with irreversible
      allograft rejection, an increased frequency of acute rejection episodes, and a
      significantly lower deceased donor graft survival, as well as in the eluates from
      rejected grafts. This review summarizes currently available information on MICA
      in the transplant setting. Undoubtedly, the questions that have surfaced surpass
      in excess the currently available answers.

PMID- 18631857
TI  - Transplant-associated hyperglycemia.
AB  - As patient survival after solid organ transplantation continues to improve,
      comorbidites associated with chronic hyperglycemia will assume increasing
      importance in limiting outcomes and quality of life. New-onset diabetes mellitus
      commonly occurs in the posttransplant setting and is associated with multiple
      complications including graft loss, cardiovascular disease, infection, and death.
      Furthermore, recent studies have begun to highlight the very high posttransplant
      prevalence and the significant cardiovascular implications of the prediabetic
      states of impaired fasting glucose and impaired glucose tolerance, indicating
      that the overall burden of transplantation-associated hyperglycemia is far
      greater than previously appreciated. Shared and distinct pathogenic factors and
      clinical repercussions exist among the organ-specific transplant scenarios.
      Diabetogenic immunosuppressive agents are common to all organ transplant
      settings, whereas glucose regulation is also strained by the restoration of
      failed hepatic and renal function. The atherogenic properties of hyperglycemia
      are particularly significant in the kidney transplant population, which has a
      marked predisposition to cardiovascular disease, whereas accelerated cardiac
      allograft vasculopathy and liver fibrosis have been associated with hyperglycemia
      in the heart and liver transplant settings, respectively. Aggressive screening
      will effectively detect transplant-associated hyperglycemia, whereas risk factor
      modification, lifestyle intervention and, where appropriate, drug therapy, may
      decrease its impact. Topics of future investigation should include the use of
      emerging diabetes therapies and avenues for the prevention and reversal of
      transplant-associated hyperglycemia.

PMID- 18631858
TI  - Evaluation and management of bone disease and fractures post transplant.
AB  - Bone disease is common in recipients of kidney, liver, heart, and lung
      transplants and results in fractures in 20-40% of patients, a rate much higher
      than expected for age. Fractures occur because of the presence of bone disease as
      well as other factors such as neuropathy, poor balance, inactivity, and low body
      or muscle mass. Major contributors to bone disease include both preexisting bone
      disease and bone loss post transplant, which is greatest in the first 6-12 months
      when steroid doses are highest. Bone disease in kidney transplant recipients
      should be considered different from that which occurs in other solid organ
      transplant recipients for several reasons including the presence of renal
      osteodystrophy, which contributes to low bone mineral density in these patients;
      the location of fractures (more common in the legs and feet in these patients
      than in spine and hips as in other solid organ recipients); and the potential
      danger in using bisphosphonate therapy, which may cause more harm than good in
      kidney transplant recipients with low bone turnover. Evaluation in all patients
      should preferably occur in the pretransplant period or early post transplant and
      should include assessment of fracture risk as well as metabolic factors that can
      contribute to bone disease. Bone mineral density measurement is recommended in
      all patients even if its predictive value for fracture risk in the transplant
      population is unproven. Management of bone disease should be directed toward
      decreasing fracture risk as well as improving bone density. Pharmacologic and
      nonpharmacologic treatment strategies are discussed in this review. Although
      there have been many studies describing a beneficial effect of bisphosphonates
      and vitamin D analogues on bone density, none have been powered to detect a
      decrease in fracture rate.

PMID- 18631859
TI  - Patient outcomes after kidney allograft loss.
AB  - Despite considerable advances in immunosuppression and in short-term graft
      survival, little improvement has been observed in long-term survival rates. About
      30% of patients lose their graft in the first 5 years, and this percentage
      increases up to 50% at 10 years. Graft losses, due to causes other than death
      with functioning graft, are an important cause of end-stage renal disease.
      Patients with failed graft account for 4% to 10% of those admitted yearly for
      dialysis therapy. There is no evidence about the superiority of hemodialysis or
      peritoneal dialysis in the treatment of these patients. Graft failure seems to be
      an important risk factor associated with morbidity and mortality, mostly in the
      first months after restarting dialysis. The causes of these high morbidity and
      mortality rates are not very well known. However, a poor control of the chronic
      kidney disease complications, the persistence of a chronic inflammatory state due
      to the failed graft, and the lack of a protective effect of the functioning graft
      could play an important role. This inflammatory state could be mediated by the
      presence of the rejected graft, and nephrectomy has been recommended. A variable
      number of patients with failed graft are relisted for a new transplant, thus
      increasing the shortage of organs. Graft survival of repeat transplantation with
      the new immunosuppressive regimens is very close to that of first-graft survival.
      Moreover, retransplantation increases patient survival rates in some series when
      compared with patients on dialysis. Complications during the first transplant
      such as BK virus nephropathy or lymphoproliferative diseases do not necessarily
      recur after the repeat transplant.

PMID- 18631860
TI  - Nonimmunosuppressive effects of mammalian target of rapamycin inhibitors.
AB  - Mammalian target of rapamycin (mTOR) integrates nutrient and hormonal signals
      involved in cell growth. Development of mTOR inhibitor drugs as therapeutic
      agents for major human diseases such as obesity, diabetes, atherosclerosis, or
      cancer will experience an important increase in the next years. The incidence of
      these diseases is particularly increased among organ transplant recipients being
      a limiting factor for transplant success. Transplant teams carry on significant
      experience in treating patients with mTOR inhibitors for preventing acute
      rejection or reducing nephrotoxicity. Preliminary data showed that these drugs
      are effective for reducing posttransplant malignancy. Transplant teams have the
      unique opportunity to analyze whether mTOR inhibitors are also effective for the
      prevention of cardiovascular diseases, obesity, and diabetes.

PMID- 18631861
TI  - Controversies in combined liver-kidney transplantation: indications and outcomes.
AB  - Controversy surrounds simultaneous transplantation of a kidney and a liver
      because the practice is increasing, and organs for transplant are limited. Not
      only do recipients of both organs use 2 rather than 1 organ, but the kidney in
      dual transplantation jumps to the front of a very long kidney wait-list.
      Furthermore, there is suspicion that some patients who undergo combined liver and
      kidney transplantation may have reversible renal failure. Likewise, inappropriate
      liver transplantation in those with end-stage renal disease is possible given the
      heavy weighting of kidney dysfunction in the calculation of the model for end
      stage liver disease score. Thus, a better way to determine the recoverability of
      renal dysfunction in liver transplant candidates and the degree of liver disease
      in end-stage renal disease is needed. Standardized strategies for candidate
      evaluation, selection, and process review are also necessary to improve organ
      allocation in those with both liver and kidney disease. However, basic and
      clinical investigation will be needed before an optimal algorithm is possible.

PMID- 18631862
TI  - Fungal infections after lung transplantation.
AB  - Lung transplantation (LT) is now considered to be the standard therapeutic
      intervention in some patients with end-stage pulmonary disease. Infectious
      complications after LT are relatively common due to the aggressive
      immunosuppression used in these receptors and local host factors derived from
      this type of transplant. The incidence of fungal infections after LT ranges up to
      30%. However, the incidence of invasive mycoses has declined over the past
      decade. These mycoses are associated with high overall mortality rates despite
      increase of the antifungal armamentarium in the last years. Candida and
      Aspergillus spp produce most of these infections, but unusual moulds such as
      Scedosporium spp are increasingly recognized as opportunistic pathogens in LT.
      This review highlights the changing spectrum of invasive fungal infections, risk
      factors, antifungal prophylaxis, diagnosis, and treatment after LT.

PMID- 18631863
TI  - Immune modulation in corneal transplantation.
AB  - Allograft rejection is the most common reason for corneal transplant failure,
      despite the immunologic privilege of both the graft and the anterior chamber. To
      prevent corneal allograft rejection, various immunomodulatory strategies have
      been used in experimental corneal transplantation. These include (1) anti-T-cell
      receptor and T-cell depletion therapy; (2) manipulation of costimulatory molecule
      function, including both down-regulation of positive stimulatory molecules and/or
      up-regulation of inhibitory molecules and overproduction of tumor necrosis factor
      related, apoptosis-induced ligand; (3) modulation of cytokine production by
      reducing proinflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]
      12, and IL-1) and/or increasing immunoregulatory cytokines (IL-10 and IL-4); (4)
      macrophage depletion; and (5) overexpression of the immunomodulatory molecule
      indoleamine 2,3-dioxygenase. Although these approaches appear promising in animal
      corneal transplantation models, there has been very little translation of these
      immunomodulatory approaches in human corneal transplantation.

PMID- 18631864
TI  - Therapeutic management of posttransplant diabetes mellitus.
AB  - Diabetes mellitus continues to be a common metabolic complication after solid
      organ transplantation. The etiology is multifactorial and includes both
      modifiable and nonmodifiable factors. Immunosuppression may play a critical role
      in its development. Targets of treatment include oral hypoglycemics as well as
      insulin. More recently, several novel agents have been approved by the Food and
      Drug Administration for treatment of type 2 diabetes. There is limited experience
      with these agents in transplant recipients. Use of oral and subcutaneous
      therapies as well as insulin will be reviewed. As diabetes has a negative impact
      on patient and graft outcome, the transplant practitioner must be vigilant in
      screening and managing diabetes after transplantation.

PMID- 18631865
TI  - mToR inhibitors-induced proteinuria: mechanisms, significance, and management.
AB  - Massive urinary protein excretion has been observed after conversion from
      calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors,
      especially sirolimus, in renal transplant recipients with chronic allograft
      nephropathy. Because proteinuria is a major predictive factor of poor
      transplantation outcome, many studies focused on this adverse event during the
      past years. Whether proteinuria was due to sirolimus or only a consequence of
      calcineurin inhibitors withdrawal remained unsolved until high range proteinuria
      has been observed during sirolimus therapy in islet transplantation and in
      patients who received sirolimus de novo. Podocyte injury and focal segmental
      glomerulosclerosis have been related to mToR inhibition in some patients, but the
      pathways underlying these lesions remain hypothetic. We discuss herein the
      possible mechanisms and the significance of mToR blockade-induced proteinuria.

PMID- 18631866
TI  - Genetic polymorphisms and the fate of the transplanted organ.
AB  - There has been an abundance of publications describing genetic variability in
      molecules affecting innate and adaptive immunity, pharmacogenetics, and other
      nonimmunological factors like the renin-angiotensin aldosterone system,
      coagulation, and fibrosis markers. Studies indicated some associations between
      polymorphisms in these candidate genes with outcomes in organ transplantation and
      underlined a potential role of genetic variability in transplantation. To be
      clinically applicable, large prospective studies must be performed to better
      define the potential benefits of genotyping on these genetic markers and clinical
      outcomes. The purposes of this review are to summarize recent data describing
      associations of polymorphisms in both immunological and nonimmunological
      molecules with transplant outcomes, with a particular emphasis on renal
      transplantation, and discuss limitations and clinical implications.

PMID- 18631867
TI  - Cancers after renal transplantation.
AB  - For patients with end-stage kidney failure, kidney transplantation improves both
      their quality of life and overall life expectancy compared with dialysis, but it
      is not without adverse effects. Cancer is second to cardiovascular disease as one
      of the major causes of morbidity and mortality in renal transplant recipients.
      Prolonged use of modern immunosuppression, which leads to alteration of immune
      function and immune surveillance, is associated with increased cancer risk. There
      is now convincing evidence from observational studies and registry data to
      confirm a 3- to 5-fold increase in overall cancer incidence, with viral-related
      neoplasia incurring the greatest risk when compare with the general population.
      Despite the increased risk, little is known about the overall cancer prognosis,
      screening, treatment strategies, and effectiveness in this population. Cancers
      can recur, occur de novo, and be transmitted from donor organs
      posttransplantation. Uncertainties exist as to how modern immunosuppressive
      agents impact on cancer management and outcomes in these patients, with some
      agents such as calcineurin inhibitors and azathioprine, being more carcinogenic
      than others. The newer agents, proliferation signal/mammalian target of rapamycin
      inhibitors and mycophenolate mofitil, may have some antiproliferative and
      antitumor activities demonstrated in preclinical and clinical studies, but long
      term well-powered trial data are needed to determine whether they are either
      protective or curative for cancers in renal transplant recipients. In this
      review, the incidence, etiology, prognosis, and potential approaches to cancer
      screening and management post-renal transplantation are discussed.

PMID- 18631868
TI  - Topics in transplant ethics.

PMID- 18631869
TI  - Situating the practice of organ donation in familial, cultural, and political
      context.
AB  - This article provides a discussion of the factors that have contributed in recent
      years to the assertion that there is a growing shortage of organs for transplant.
      Findings from ethnographic research carried out in 3 settings--the United States,
      Japan, and Mexico--are then presented to demonstrate that factors other than low
      education levels, irrationality, or a lack of generosity are at work when
      individuals make decisions about organ donation. In all 3 sites, it is clear that
      both the donation and receiving of organs are based on moral positions and felt
      obligations concerning appropriate behavior among close relatives and that the
      ideal of autonomous choice is not readily applicable. Culturally informed
      expectations are at work in all 3 sites, and in Japan and Mexico, social and
      political dimensions additionally come into play. We argue that a better
      accounting is called for of the familial, cultural, and political contexts within
      which organ transfer takes place.

PMID- 18631870
TI  - Preferred allocation for registered organ donors.
AB  - A shortage of transplantable organs in the United States can be traced to low
      rates of donation. Incentives for organ donation might partially remedy these
      organ shortfalls. Although incentives countervail the dominant philanthropy
      model, this model is neither well supported by ethical argument nor strictly
      applied. Preferred allocation, consisting in the practice of awarding extra
      priority points to previously registered organ donors who need transplants, is
      attractive in that it offers a potentially effective incentive while deviating
      less radically from entrenched practices than financial incentives. It is
      supported by the public and conforms to intuitions about justice and reciprocity.
      Moreover, it highlights moral features of the transplant community as a
      particular moral community within the greater medical community.

PMID- 18631871
TI  - The emergence of "personhood" in organ procurement.
AB  - This article begins and ends with an account of the actions of one person. I
      propose that such heroics are rooted in an instinctual recognition of
      "personhood" as it emerges from a particular human "other." I propose that
      heroism grounded in the recognition of "personhood" is descriptive of those acts
      of organ donation that are founded on free will. The moral principles involved in
      deliberations for organ transplantation can provide a duplication of concerns
      (recipient and donor). However, the enterprise of organ transplantation
      increasingly depends on the altruism of free-will donation, the adherence to
      donor qualifications, and the defense of human rights.

PMID- 18631872
TI  - Matching graft to recipient by predicted survival: can this be an acceptable
      strategy to improve utilization of deceased donor kidneys?
AB  - A new kidney allocation scheme is needed to address the current shortage of
      deceased donor kidneys for transplantation in the United States. With this goal
      in mind, we have derived a novel utility-based system to balance supply and
      demand. Our system uses a North American-based recipient risk score and the
      deceased donor score to maximize the total number of years of renal allograft
      function as a means to improve allocation of kidneys from deceased donors.
      Essentially, donor renal allografts are matched to a wait-listed candidate with
      similar predicted survival, which poses an ethical issue. However, this novel
      utility-based system is practical and could improve deceased donor renal
      allocation by minimizing both waste and need for retransplantation.

PMID- 18631873
TI  - Ethical analysis and consideration of health behaviors in organ allocation: focus
      on tobacco use.
AB  - Health behaviors are significantly understudied in transplant patients,
      contributing to significant ethical debate among transplant professionals. Some
      of these health behaviors (tobacco use and overweight/obesity) are the leading
      preventable causes of mortality in the US general population and likely have a
      higher prevalence and impact among transplant populations. For example, tobacco
      use has been linked to worse graft survival, patient survival, complications, and
      comorbidities, whereas tobacco cessation has been associated with improved
      patient and graft survival. Over time, transplant professionals increasingly
      believe that tobacco use should be a relative contraindication to organ
      allocation. That belief seems to be strengthened after provider education on
      pertinent evidence linking tobacco use to medical consequences in both the
      general and the transplant populations. A core framework for ethical analysis of
      health behaviors in the context of organ allocation is described, using concepts
      of utility, justice, and respect for all persons. This framework is designed to
      help transplant professionals discuss and formulate policy on consideration of
      health behaviors in the context of organ allocation. More research is needed to
      advance our knowledge of the impact of health behaviors on transplant patient
      outcomes.

PMID- 18631874
TI  - Case studies in transplant ethics.
AB  - Clinicians and other health care professionals involved in the evaluation and
      management of organ transplant recipients and organ donors quite commonly
      encounter ethically complex scenarios during the course of their work. The
      response to such challenging situations may be influenced by personal experiences
      and beliefs, programmatic or institutional policy, existing legislation,
      published literature, and consultative analysis by experts in the field of
      biomedical ethics. As organ transplantation continues to evolve in its scope,
      complexity, and global reach, there is a growing need for transplant programs to
      carefully discuss and reach consensus on how to deal with specific ethical issues
      that may arise. In this article, we present the summaries of 3 clinically
      relevant case scenarios from the 2007 Mayo Clinic Course in Transplant Ethics,
      along with the results of audience responses and discussion facilitated by a
      volunteer panel of experts from North America. The cases provide cogent examples
      of how open, consensus-driven discussion of specific ethically charged scenarios
      can be useful in guiding progressive clinical practices in organ transplantation.

PMID- 18631875
TI  - Ethical controversies in public solicitations for organs.
AB  - The increased shortage of organs for transplantation has led to a widening of the
      living donor pool and to innovations in how and where people seek living donors.
      Transplant programs are being asked to reconsider practice in light of new
      situations. Public solicitations for organs have grown as people have become more
      desperate to find organs. The expansion of the media, particularly the Internet,
      into our everyday lives has offered an additional method for the dissemination of
      information and requests for organs. This article discusses public solicitations
      from living kidney donors, examines the ethical issues therein, and makes
      suggestions as to how transplant teams might consider addressing this issue.

PMID- 18631876
TI  - Expanding criteria for living kidney donors: what are the limits?
AB  - The need to evaluate potential living kidney donors is more pressing than ever
      before. Evaluating the potential medical risks to individual donors presents both
      medical and ethical questions related to quantitative hazards of donor
      nephrectomy. These include conditions commonly associated with age, such as the
      decline in glomerular filtration rate, the rise in arterial pressures, and weight
      gain. The "normal" ranges for many of these characteristics are changing as their
      importance as predictors of cardiovascular risk is reevaluated and the duration
      of exposure for a lifetime is considered. Many older donors in good health favor
      donating a kidney to a spouse, despite the presence of elevated blood pressure or
      even impaired glucose tolerance. The Mayo Kidney/Pancreas transplant program
      established an "extended criteria workgroup" to address these issues on an
      individual basis. Our program now stratifies medical criteria based upon age,
      allowing more liberal criteria for older donors. As a result, we accept treated
      hypertension in white donors, emphasizing the importance of informed consent and
      the need for vigilant follow-up. Our greatest concern relates to the development
      of obesity, particularly in younger individuals. Many of the long-term results of
      kidney donation are likely to hinge upon future behavior, including smoking,
      weight management, and medical follow-up care. Older donors are more likely to
      have established behavior patterns, an element that makes them better candidates
      in many respects. Studies to closely track the impact of donor nephrectomy in the
      current era with changing population demographics and expectations are essential.

PMID- 18631877
TI  - Psychosocial factors in living organ donation: clinical and ethical challenges.
AB  - Living donor surgery has come to the forefront of public attention because
      increasing numbers of potential donors respond to the organ shortage. Because of
      several factors including decreased morbidity from donor surgery, online
      resources appealing for organs, and increased publicity about donation, new
      populations of unrelated donors are seeking evaluation for donor surgery.
      However, concern about potential coercion of vulnerable individuals, the
      potential for adverse psychosocial outcomes, and recent reports of donor deaths
      have reinvigorated discussion within the medical community about how best to
      assess donors. Research on the long-term quality of life outcomes for donors
      suggests that most donors are satisfied with their decision to donate. Small
      single-center studies on psychosocial outcomes have reported psychiatric sequelae
      after donor surgery. Little is known about the psychosocial outcomes for donors
      who are psychosocially excluded from donating. A multidisciplinary team approach,
      including social work and psychiatry evaluations, allows for the comprehensive
      assessment of important areas including motivation and expectations about
      surgery, current and past psychiatric conditions, history of substance or alcohol
      abuse, family support, understanding of the risks and alternatives of donor
      surgery for the donor and recipient, and motivation for donation including any
      evidence of coercion.

PMID- 18631878
TI  - The live organ donor's consent: is it informed and voluntary?
AB  - Live organ donors represent nearly 50% of the solid organ donors in the United
      States. This unique population of individuals accepts risk for the benefit of
      another. The main justification by the medical community for permitting such risk
      to live donors has been respect for their autonomy, realized through the practice
      of informed consent. This article examines the key criteria of informed consent-
      understanding and non-control (voluntariness)--in the context of live organ
      donation. It concludes that more prospective studies are needed to improve the
      process of informed consent in this population.

PMID- 18631879
TI  - Responding to offers of altruistic living unrelated kidney donation by group
      associations: an ethical analysis.
AB  - Members of a religious community presented to our institution and offered to be
      altruistic unrelated living kidney donors en masse. This situation raised a
      number of ethical concerns related to the situation specifically and to
      altruistic unrelated living kidney donation in general. Based on our ethical
      analysis, we made the following conclusions. Altruism is a legitimate motive for
      living unrelated kidney donation, and altruistic acts can be based legitimately
      on religious beliefs. Retrieval of kidneys from living donors is generally safe,
      and altruistic donors may derive benefit from donating (eg, enhanced self-esteem)
      assuming they are autonomous and free of coercion. Separate teams should evaluate
      and care for potential donors and recipients to avoid compromising the donor
      screening process and to ensure potential donors satisfy medical and psychosocial
      criteria for donation. Indeed, transplant clinicians should not assume that
      potential unrelated living kidney donors are not susceptible to coercion. In
      fact, in our situation, coercion was our biggest concern. Appointing a donor's
      advocate can facilitate donor understanding of the risks, benefits, and
      alternatives to organ donation and can help discern coercion. Furthermore, an
      experienced social worker should assess all potential donors and discern if
      coercion is present; potential donors should be referred to a psychologist or
      psychiatrist as appropriate. Although concerns regarding allocation were not
      raised by our specific situation, ethical concerns regarding allocation of
      kidneys donated by altruistic unrelated kidney donors exist (eg, requesting that
      such donations be allocated to recipients with specific characteristics).

PMID- 18631880
TI  - Ethical dimensions of living donation: experience with living liver donation.
AB  - Whereas distributive justice is the most important principle in most aspects of
      transplantation and the allocation of scarce resources, it is far less of a
      central principle in directed living liver donation. For living donation, the
      ethical principals include (1) respect for the donor's autonomy through full,
      voluntary, informed consent; (2) beneficence; and (3) nonmaleficence. But how do
      we put these principles into practice? Practical decision making in living liver
      donation involves 3 fundamental ethical dimensions: (1) need, (2) probability of
      donor safety, and (3) the chance for good short- and long-term recipient
      outcomes. These same dimensions exist everywhere, but the size and shape of the
      "triangle" can vary greatly depending on societal beliefs. Ultimately, the proper
      balance of ethical equipoise is affected by the dynamics of these 3 dimensions.

PMID- 18631881
TI  - Future issues in transplantation ethics: ethical and legal controversies in
      xenotransplantation, stem cell, and cloning research.
AB  - With little prospect of developing a sufficient supply of human transplantable
      organs to meet the large and growing demand, attention has turned to
      xenotransplantation, as well as stem cell and cloning research, as possible
      approaches for alleviating this allograft shortage. This article explores ethical
      and legal issues that surround developments in these fields.

PMID- 18631882
TI  - Alternative sources of pluripotency: science, ethics, and stem cells.
AB  - Despite many advances in human embryonic stem cell (hESC) technology the ethical
      dilemma involving the destruction of a human embryo is one factor that has
      limited the development of hESC based clinical therapies. Two recent reports
      describing the production of pluripotent stem cells following the in vitro
      reprogramming of human somatic cells with certain defined factors illustrate one
      potential method of bypassing the ethical debate surrounding hESCs (Yu J,
      Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived
      from human somatic cells. Science. 2007 Dec;318(5858):1917-1920; Takahashi K,
      Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human
      fibroblasts by defined factors. Cell. 2007 Nov;131(5): 861-872.). Other
      alternative methods include nuclear transfer, altered nuclear transfer, and
      parthenogenesis; each with its own set of advantages and disadvantages. This
      review discusses recent advances in these technologies with specific focus on the
      issues of embryo destruction, oocyte recovery, and the potential of each
      technology to produce large scale, patient specific cell transplantation
      therapies that would require little or no immunosuppression.

PMID- 18631883
TI  - Journal of Pediatric Urology. Editorial.

PMID- 18631884
TI  - Congenital urological anomalies diagnosed in adulthood - management
      considerations.
AB  - OBJECTIVE: Despite worldwide availability of prenatal ultrasound, many patients
      are diagnosed in adult life with congenital anomalies such as ureteropelvic
      junction obstruction (UPJO), undescended testicle (UDT), ureterocele,
      hypospadias, vesicoureteral reflux (VUR) and primary obstructing megaureter
      (POM). The aim of this review was to describe these clinical conditions and their
      suggested management based on the available medical literature. REVIEW: Adult
      UPJO is not a rare condition; symptomatic patients should be treated rather than
      observed. Treatment options are nephrectomy for non-functioning kidneys and
      reconstructive surgery for functioning renal units. The adult UDT has low
      fertility potential and increased cancer risk; hence most of the data in the
      literature indicate performing an orchiectomy. Adult ureteroceles are usually
      related to single systems and they are intravesical and less obstructive. For
      symptomatic patients endoscopic incision showed high efficacy for symptom
      elimination with minimal side effects. Primary hypospadias correction in the
      adult patient is feasible, but success rates are low compared to the pediatric
      age group. Secondary correction, whether primary correction was performed in
      childhood or adulthood, is a challenging task with a high complication rate.
      Treatment decisions regarding adult patients with VUR are difficult to make as
      the available data are inconsistent; there is no strict evidence that reflux in
      an adult is directly related to renal growth impairment, ascending
      pyelonephritis, and/or embryo loss in a pregnant woman. In contrast to the
      pediatric age group, adult POM is usually a symptomatic condition and related to
      a high complication rate including infections, stone formation and renal failure.
      Spontaneous resolution is rare and hence active surgical management is advocated.
      CONCLUSION: Congenital urological anomalies identified in adulthood are not rare
      and pose a management challenge to the urologist. For most of the reviewed
      diseases, evidence-based management direction is difficult due to a lack of
      randomized trials and long-term follow up.

PMID- 18631885
TI  - Bladder augmentation and artificial sphincter implantation: urodynamic behavior
      and effects on continence.
AB  - OBJECTIVE: To quantify changes in bladder capacity, pressure and compliance after
      isolated bladder augmentation or augmentation associated with implantation of an
      artificial sphincter, and to compare the various types of augmentation. PATIENTS
      AND METHODS: Preoperative and postoperative urodynamic studies were performed in
      a group of 38 patients (18 males and 20 females; age range 2-19 years), who
      underwent a type of bladder augmentation. RESULTS: The bladder improved in
      capacity in all patients (mean values: initial 137 ml, final 336 ml, individual
      increase 229 ml; 434%) except two, in which the augmentation was done with
      ureter. The mean pressure improved (initial 32 cm of H(2)O, final 14, decrease
      per patient 18 cm of H2O; 49%). The curve of compliance, progressively increasing
      typical of hyperreflexia and poor compliance, present in 70% of the cases
      preoperatively, improved in 78% cases postoperatively, although there were
      several different patterns. Urodynamic behavior was analyzed with regard to the
      tissue used for augmentation (ileum, ureter or sigmoid colon). In the sigmoid
      colon group, there were no significant differences in the urodynamic behavior of
      the bladder neo-reservoir in relation to the configuration used. CONCLUSION: With
      bladder augmentation comes an increase in bladder capacity, a reduction in
      pressure, and an improvement in compliance and continence. The level of change in
      capacity, pressure and compliance varies with the tissue used and the length and
      caliber of the insert. When the procedure is carried out using sigmoid colon
      tissue, there are no noteworthy differences among the various possible
      configurations.

PMID- 18631886
TI  - The appendix as ureteral substitute: a report of 10 cases.
AB  - BACKGROUND: Ureteric replacement in part or in total is rarely needed in
      children. We present our experience in using the appendix to replace the ureter.
      METHODS: A retrospective case note review was carried out at Sheffield Children's
      Hospital (UK), Ekta Institute of Child Health (Raipur, Chhattisgarh, India) and
      Christian Medical College Hospital (Vellore, India) of all cases of ureteric
      substitution using the appendix. RESULTS: Ten patients were identified, operated
      in 2002-2007: seven males and three females with a median age of 2.5 years (range
      2.5 months to 12 years). The reasons for ureteric replacement were traumatic
      ureteric avulsion (n=1), congenital ureteric stenosis (n=5), non-drainage
      following previous pyeloplasty for pelvi-ureteric junction obstruction (n=3) and
      ureteric stricture following reimplantation for vesico-ureteric reflux (n=1). The
      appendix was used in an anti-peristaltic manner in all cases, and in one case a
      transureteroureterostomy was performed. At a median follow up of 16months (1-72
      months), all the patients were well except one whose kidney function had
      deteriorated. CONCLUSIONS: Total or partial replacement of the ureter using the
      appendix, even in the first year of life, preserved renal function in nine cases.
      Ureteric continuity can be successfully restored in children using the appendix.

PMID- 18631887
TI  - Health-related quality of life in children with vesicoureteral reflux - impact of
      successful endoscopic therapy.
AB  - OBJECTIVES: Endoscopic therapy for vesicoureteral reflux (VUR) using
      dextranomer/hyaluronic acid (Dx/HA) has become increasingly popular, but the
      subjective impact of this therapy and subsequent reflux resolution on health
      related quality of life (HRQoL) remains unclear. The aim of this study was to
      address this issue. MATERIALS AND METHODS: One hundred children (65 girls, 35
      boys; mean age 4.46 years) cured of primary VUR by endoscopic treatment were
      retrospectively reviewed. The Glasgow children's benefit inventory (GCBI) - a
      validated, reproducible, post-interventional questionnaire consisting of four
      subscales - supplemented by sociodemographic and disease-specific questions was
      employed. The HRQoL benefit was calculated on a scale ranging from -100 (complete
      failure) to +100 (complete success) and correlated with supplementary data.
      RESULTS: Total response rate was 88%. Mean total GCBI score was 28.4+/-20.3
      representing a significant HRQoL amelioration. All GCBI subscores improved with
      the physical health subscale being most relevant. A gender-specific, significant
      difference in relative GCBI scores was discovered. Correlation with critical life
      events and time since operation proved the positive effect on HRQoL to be
      durable. CONCLUSIONS: Resolution of primary VUR secondary to Dx/HA treatment
      significantly improves HRQoL. HRQoL is positively affected in many areas and not
      only in those directly associated with VUR. These improvements are not temporary,
      suggesting that successful Dx/HA therapy may be superior to medical management in
      terms of children's quality of life.

PMID- 18631889
TI  - Comparison of magnetic resonance urography with ultrasound studies in detection
      of fetal urogenital anomalies.
AB  - PURPOSE: Prenatal ultrasonography detects the vast majority of urogenital
      anomalies, but in some cases the diagnosis remains in doubt. We assessed the
      potential of magnetic resonance urography (MRU) in the evaluation of different
      urogenital anomalies in fetuses when ultrasound study was equivocal. PATIENTS AND
      METHODS: We retrospectively reviewed the medical records of 46 fetuses in whom
      the presence of urogenital anomalies was suspected at ultrasound studies, but
      remained inconclusive. Fetal MRU was performed within the same week as ultrasound
      studies. All patients underwent MRU, comprising overview, fast, thick-slab,
      heavily T2-weighted sequences, followed by focused, high-resolution T2-weighted
      sequences obtained in sagittal, axial and coronal planes. T1-weighted sequences
      were obtained in selected cases for assessment of the gastrointestinal tract. All
      MRU results were compared with ultrasound findings. Sensitivity of each imaging
      modality was estimated based on definite diagnoses made after birth or abortion.
      RESULTS: The mean (range) gestational age was 27 (18-36)weeks. The final
      diagnosis was ureteropelvic junction obstruction in 12, ureteral dilation (due to
      vesicoureteral junction obstruction) in five, ureterocele in five, posterior
      urethral valve in 16, multicystic dysplastic kidney in six, mesenteric cyst in
      one and abdominoscrotal hydrocele in one. Overall diagnostic sensitivity of fetal
      MRU was 96% compared to sonography with 58% sensitivity (p<0.05). Fetal MRU
      studies provided additional information to sonography in 17 (37%) cases, and were
      especially more sensitive in evaluation of ureteral anatomy. CONCLUSIONS: Fetal
      MRU can accurately diagnose a wide variety of urinary tract disorders and must be
      regarded as a valuable complementary tool to ultrasound in the assessment of the
      urinary system, particularly in cases of inconclusive ultrasound findings. The
      present study had a selection bias, as only fetuses with possible anomalies
      proposed by sonography were referred for MRU; however, this is the population
      that probably benefits most from MRU studies.

PMID- 18631888
TI  - Enterocystoplasty in children with neuropathic bladders: long-term follow-up.
AB  - OBJECTIVE: This study assesses clinical outcome, after at least 8 years, of
      augmentation done before or at puberty in neuropathic bladders. PATIENTS AND
      METHODS: A total of 29 children with neuropathic bladders who did not respond
      satisfactorily to clean intermittent catheterisation and anti-cholinergic therapy
      underwent enterocystoplasty at a mean age of 11.8 years (range 3-18). Twenty-one
      children (72.4%) had vesicoureteral reflux (VUR) and/or ureterohydronephrosis and
      22 (75.8%) had dimercapto-succinic acid scars, but all had normal renal function.
      All patients were followed at regular intervals with urinary tract imaging, serum
      electrolytes, creatinine, urodynamic evaluation and 24-h urine collection. Urine
      cytology, cystoscopy and biopsy were performed at the end of follow-up. RESULTS:
      Mean follow-up was 11 years (range 8-14.5) and mean age at the end of follow-up
      was 22.2 years (range 13.2-31). Urodynamic studies showed a significant
      improvement in bladder compliance in all patients. Upper urinary tract dilatation
      disappeared in all, VUR in 13/17 (76.4%), and no new renal scarring occurred in
      any patient. At the end of follow-up, renal function was normal in all according
      to serum creatinine, but cystatin C levels were normal in 27 and elevated in two.
      Significant proteinuria and low concentrations of renin and aldosterone were
      present in 80% and 82%, respectively. Only one patient had urinary tract
      infection, three had bladder stones, and in another a catheterisable channel was
      made. All patients were dry with normal urine cytology and cystoscopy, and no
      malignant lesions have been found in the biopsy specimens. CONCLUSION:
      Enterocystoplasty has preserved renal function and resolved VUR and/or
      hydronephrosis in most patients. The future implications of proteinuria and the
      low serum levels of renin and aldosterone, as well as the best indicator for
      measuring renal function, have yet to be determined. Close, life-long follow-up,
      including cystoscopy, is necessary to prevent complications.

PMID- 18631890
TI  - Intestinal bladder augmentation at school age has no adverse effects on growth.
AB  - PURPOSE: Intestinal bladder augmentation predisposes the patient to many
      complications. The aim of this study was to determine whether augmentation has an
      adverse effect on growth. MATERIALS AND METHODS: Longitudinal growth data were
      collected and analyzed for nine patients with bladder exstrophy and augmentation,
      and compared with the growth data of 13 exstrophy patients without augmentation.
      Augmentation was performed at a median age of 10.3 years (range 6.3-13.2). The
      median follow up was 5.4 years (range 3.6-9.1). RESULTS: The median height Z
      score at age 10 years was -0.4 (range -1.8 to +1.5) in patients who later
      received augmentation and -0.2 (-2.1 to +1.7) in the non-augmented group. Their
      median heights at latest follow up were -0.7 (-1.6 to +1.9) and 0.0 (range -1.8
      to +1.1), respectively. The adult height of three patients with and 13 patients
      without augmentation was normal. CONCLUSIONS: Intestinal bladder augmentation
      performed at school age has no adverse effects on longitudinal growth in patients
      with bladder exstrophy. Most of the patients with bladder exstrophy have normal
      growth.

PMID- 18631891
TI  - A new algorithm for management of chordee without hypospadias based on
      mobilization of urethra.
AB  - OBJECTIVE: To assess the feasibility of chordee correction by mobilization of
      urethra with corpus spongiosum, and define the guidelines for management of
      chordee without hypospadias. PATIENTS AND METHODS: We reviewed 25 cases of
      chordee without hypospadias, managed in 1992-2005. Age of patients ranged from 3
      to 28years (mean 14.4years). Chordee correction was performed on a case-by-case
      basis by skin de-gloving, mobilization of divergent corpus spongiosum,
      mobilization of hypoplastic urethra, mobilization of proximal urethra up to
      bulbar urethra, dorsal plication and division/resection of hypoplastic urethra
      with main emphasis on mobilization of urethra, and confirmed by Gittes test.
      RESULTS: Chordee correction was possible by mobilization of urethra after penile
      degloving in 76% of cases and dorsal plication after urethral mobilization in 8%.
      Only 16% required division/resection of hypoplastic urethra. None of them had
      residual chordee in follow-up period of 6months-3years (mean of 26months). After
      fistula repair and internal urethrotomy in one patient each, a second surgery had
      100% success. CONCLUSIONS: We propose an algorithm based on mobilization of
      urethra that defines the etiology and guidelines for the management of chordee
      without hypospadias.

PMID- 18631892
TI  - Third trimester ultrasound of fetal pyelectasis: predictor for postnatal surgery.
AB  - OBJECTIVE: The ability to predict surgically relevant fetal renal pyelectasis is
      limited. We sought to determine whether the intrauterine timing of prenatal
      pyelectasis can predict the need for postnatal surgery. METHODS: We
      retrospectively reviewed all patients with ultrasound measurements of the fetal
      renal pelvis during the 2nd and 3rd trimesters and postnatally. Pyelectasis was
      defined as >7mm for renal pelvis antero-posterior diameter in the 2nd trimester
      and >10mm in the 3rd trimester. RESULTS: Fifty-nine patients out of 2397
      candidates met the criteria for inclusion. A total of 116 kidneys were analyzed
      independently. Second trimester pyelectasis was associated with grade of
      postnatal hydronephrosis but not the need for surgery. Third trimester
      pyelectasis was associated with both postnatal hydronephrosis and surgery. The
      positive and negative predictive values for postnatal surgery were respectively
      18% and 95% in the second trimester, and 27% and 100% in the third trimester.
      CONCLUSIONS: Third trimester ultrasound for fetal pyelectasis was better able to
      predict surgically relevant hydronephrosis than second trimester ultrasound.

PMID- 18631893
TI  - Differing urinary urea excretion among children with idiopathic hypercalciuria
      and/or hyperuricosuria.
AB  - OBJECTIVE: To estimate dietary protein intake in children with idiopathic
      hypercalciuria (HC) and/or hyperuricosuria (HU). PATIENTS AND METHODS: We
      compared the 24-h urinary excretion of urea, as a reflection of protein intake,
      in four age- and sex-matched groups, each comprising 56 consecutive children: (1)
      HC, (2) HU, (3) HC+HU and (4) control. RESULTS: Urinary urea excretion was
      significantly higher in HC, HU and HC+HU than in controls. HC and HU children had
      similar urea excretion. HC+HU children had urinary urea significantly higher than
      HC and HU, but urinary calcium similar to HC and urinary uric acid excretion
      similar to HU subjects. Urinary calcium was significantly (R(2)=0.21) correlated
      with urea excretion in HC children only, whereas urinary uric acid was
      significantly (R(2)=0.21) correlated with urinary urea in HU children only. No
      significant correlation between urinary urea and calcium or uric acid excretion
      was found in HC+HU patients although they had the highest urinary urea. A
      significant (p=0.004) interaction between urinary urea and sodium in increasing
      urinary calcium excretion resulted only in the HC group. CONCLUSION: The
      association of dietary protein excess with HC and/or HU is conditioned by an
      individual (genetic?) predisposition and may be produced by different mechanisms.

PMID- 18631894
TI  - Plasma renin activity for monitoring vesicoureteric reflux therapy: mid-term
      observations.
AB  - OBJECTIVE: To study plasma renin activity (PRA) as an early marker for monitoring
      treatment of vesicoureteric reflux (VUR). PATIENTS AND METHODS: Fifty-nine
      children (35 males and 24 females), mean age 43.3+/-26.5 (range 4.5-89) months,
      with various grades (I-V) of primary VUR were enrolled. PRA, renal scars, split
      renal function (SRF), glomerular filtration rate (GFR), serum creatinine, blood
      pressure and episodes of breakthrough urinary tract infection were monitored at
      regular intervals. Surgery was performed as per currently accepted criteria. PRA
      values were used for post-hoc analysis of results. RESULTS: Thirty-eight children
      (64.4%) underwent anti-reflux surgery during the mean follow up of 17.1+/-3.1
      months; 21 (35.6%) continued on non-operative follow up. Rise in PRA up to the
      time of surgery was seen in all patients. It normalized after surgery in 86%, and
      reduced but plateaued at a higher level than normal in 13.8% in the surgical
      group. While improvement in SRF and GFR was seen only in 2/38 (5.2%) and 12/38
      (31.6%), respectively, blood pressure stabilized in 30.7% and serum creatinine
      showed inconsistencies. In non-operatively managed cases, improvement in SRF was
      seen in only one case and GFR in 14.2% of cases. However, 80.9% children showed a
      progressive rise in PRA throughout the period of non-operative follow up.
      CONCLUSION: Current end points of non-operative management already cause
      irreversible renal damage by the time surgery is indicated. Our results suggest
      that serial measurement of plasma renin activity may help in better
      stratification of patients with moderate to high grade (III-V) VUR with respect
      to management and prognosis.

PMID- 18631895
TI  - Complications of radical soft-tissue mobilization procedure as a primary closure
      of exstrophy.
AB  - PURPOSE: The radical soft-tissue mobilization procedure was developed as a
      component of the staged closure of classical bladder exstrophy to improve
      continency rates without having to perform pelvic osteotomies. The authors
      describe complications following this procedure and discuss possible etiologies
      and subsequent management. MATERIALS AND METHODS: We extracted from an
      institutionally approved exstrophy database the records of patients evaluated for
      complications following radical soft-tissue mobilization repair from 1999 to
      2002. RESULTS: Four patients were referred to our institution following closure
      of exstrophy with the radical soft-tissue mobilization technique; two boys and
      two girls. Complications included ischemic penile injuries in both males, failed
      exstrophy closure in one female, incontinence with need for bladder neck
      transection and diversion in two patients, and upper tract deterioration in two
      patients of whom one required cystectomy and incontinent diversion. CONCLUSIONS:
      Omission of osteotomies when employing the radical soft-tissue mobilization
      repair appears to result in complications that could otherwise be prevented.
      Additionally, the complex dissection of the pelvic musculature, innervation and
      vasculature performed during radical mobilization has great potential to injure
      the pelvic structures and genitalia, as has been seen with the cases presented
      herein.

PMID- 18631896
TI  - Leech in urinary bladder causing hematuria.
AB  - OBJECTIVE: To estimate efficacy of normal saline in the management of hematuria
      caused by accidental entry of a leech per urethra into the urinary bladder.
      METHODS: An intervention study was carried out in the Department of Pediatric
      Surgery of Sylhet MAG Osmani Medical College between January 1998 and December
      2003. A total of 43 boys (mean age 8 years, SD+/-2.6) were enrolled. In all
      cases, a leech had entered the urinary bladder through the urethra causing
      hematuria. All patients were equipped with a self-retaining Foley catheter. They
      were managed by infusing 50ml of normal saline into the urinary bladder through
      the catheter that was then clamped for 3h. RESULTS: After removing the catheter,
      in all cases the whole leech was spontaneously expelled intact, dead or alive,
      within 2-24h during the subsequent act of micturition. Hematuria gradually
      diminished to a clear flow within the next 6h in 27 cases, 12h in 14 cases and
      24h in two cases. All patients were followed up for 2 weeks, and none developed
      recurrent hematuria. CONCLUSION: Catheterization and irrigation of the urinary
      bladder with normal saline is a relatively simple, safe and inexpensive method of
      removing the leech and controlling hematuria.

PMID- 18631897
TI  - Magnetic resonance urography in pediatric urology.
AB  - PURPOSE OF REVIEW: Magnetic resonance urography (MRU) has emerged as a powerful
      diagnostic tool in the evaluation of the pediatric genitourinary tract. The
      purpose of this review is to familiarize the reader with the basic techniques,
      strengths and limitations, as well as the current and potential future
      applications of MRU in pediatric urology. RECENT FINDINGS: MRU can provide
      detailed anatomical information and assess renal function and drainage in a
      single study. MRU does not employ ionizing radiation and may be utilized in
      patients with iodine-based contrast allergy or impaired renal function. MRU has
      been most often applied to the evaluation of hydronephrosis and provides valuable
      insight into a wide range of obstructive uropathies. MRU was shown to be superior
      to renal scintigraphy for the diagnosis of pyelonephritis and renal scarring. The
      use of MRU for the assessment of urolithiasis and vesicoureteral reflux is
      limited and technical refinements are required. Potential future applications
      include fetal MRU, virtual endoscopy, and MRU-guided procedures. The development
      of new contrast agents and new image-processing software will further enhance the
      diagnostic potential of MRU in pediatric urology. SUMMARY: MRU is currently
      thought of as a problem-solving tool to define anatomy and function when
      conventional methods fall short. This technique is likely to emerge as the
      imaging modality of choice for children with complex genitourinary pathology.

PMID- 18631898
TI  - A rare case of positive prenatal intervention by early delivery for fetal
      hydronephrosis.
AB  - A male fetus followed for prenatal hydronephrosis thought to be bilateral
      ureteropelvic junction (UPJ) obstruction experienced severe acute oligohydramnios
      at 30 weeks gestation and was delivered at 32 weeks by Cesarean section.
      Postnatal bilateral UPJ obstruction was confirmed and anuria documented along
      with renal failure. Percutaneous nephrostomies were performed with reversal of
      the renal failure, and bilateral pyeloplasties were performed with a good
      outcome.

PMID- 18631899
TI  - Calcification in a Deflux bleb thought to be a ureteral calculus in a child.
AB  - A child admitted for abdominal pain was evaluated with an abdominal computed
      tomography scan. Calcification was noted at the ureterovesical junction. The
      child had undergone successful bilateral Deflux injection 3 years earlier. No
      hydronephrosis was noted and an intravenous pyelogram was normal. Ureteroscopy
      revealed no intraluminal stones, and a follow-up scan showed the lesion to be
      still present and unchanged. This case illustrates that calcifications within a
      Deflux bleb can be mistaken for a ureteral calculus, and the entire clinical
      picture should be kept in mind when evaluating a patient with abdominal pain. Due
      to the widespread use of Deflux to treat vesicoureteral reflux, this phenomenon
      may be seen more frequently as this population ages.

PMID- 18631900
TI  - Laparoscopic nephrectomy for the management of renal medullary carcinoma in a
      child.
AB  - Renal medullary carcinoma is a lethal subtype of renal cancer that afflicts
      patients with sickle-cell hemoglobinopathies. Here we present the case of a 13
      year-old boy with renal medullary carcinoma who is the first, to our knowledge,
      to be managed using a planned laparoscopic radical nephrectomy.

PMID- 18631901
TI  - Bilaterally obstructed ureteropelvic junction of the upper moieties in a complete
      duplex collecting system.
AB  - Maternal ultrasound is a routine examination in prenatal evaluation. The number
      of fetal abnormalities detected has been increasing, and includes fetal
      hydronephrosis which is secondary to ureteropelvic junction obstruction in 80% of
      cases. We report a case of a 1-year-old female infant with hydronephrosis
      prenatally detected by ultrasound. After close postnatal follow-up and diagnosis,
      she eventually underwent a definitive reconstructive procedure. This is the first
      reported case of a bilateral ureteropelvic junction obstruction of the upper
      moieties of a duplex collecting system.

PMID- 18631902
TI  - Journal of Pediatric Urology. Editorial.

PMID- 18631903
TI  - A randomized controlled trial of the effectiveness of osteopathy-based manual
      physical therapy in treating pediatric dysfunctional voiding.
AB  - OBJECTIVE: Pediatric dysfunctional voiding (DV) presents physical and emotional
      challenges as well as risk of progression to renal disease. Manual physical
      therapy and osteopathic treatment have been successfully used to treat DV in
      adult women; a pediatric trial of manual physical therapy based on an osteopathic
      approach (MPT-OA) has not been reported. The aim of this study was to determine
      whether MPT-OA added to standard treatment (ST) improves DV more effectively than
      ST alone. METHODS: Twenty-one children (aged 4-11 years) with DV were randomly
      assigned to receive MPT-OA plus standard treatment (treatment group) or standard
      treatment alone (control group). Pre-treatment and post-treatment evaluations of
      DV symptoms, MPT-OA evaluations and inter-rater reliability of DV symptom
      resolution were completed. RESULTS: The treatment group exhibited greater
      improvement in DV symptoms than did the control group (Z=-2.63, p=0.008, Mann
      Whitney U-test). Improved or resolution of vesicoureteral reflux and elimination
      of post-void urine residuals were more prominent in the treatment group.
      CONCLUSIONS: Results suggest that MPT-OA treatment can improve short-term
      outcomes in children with DV, beyond improvements observed with standard
      treatments, and is well liked by children and parents. Based on these results, a
      multi-center randomized clinical trial of MPT-OA in children with vesicoureteral
      reflux and/or post-void urinary retention is warranted.

PMID- 18631904
TI  - Evolving management of adolescent varicocele.
AB  - OBJECTIVE: To review the evolution in indications for treatment and treatment
      modalities for adolescent varicocele at our centre, and evaluate the impact of
      varicocelectomy on final outcome. PATIENTS AND METHODS: Between 1995 and 2006, we
      treated 242 left varicoceles. Preoperative assessment included clinical
      evaluation, measurement of testicular volumes, and colour-Doppler ultrasound
      (CDUS). A subinguinal varicocelectomy was performed in 124 patients (group A),
      and a laparoscopic non-artery-sparing Palomo procedure in the remaining 118
      (group B). In group B patients, CDUS was also used to investigate the functional
      anatomy of varicocele, and all the veins found to be refluxing were divided
      during surgery. The two groups were compared with regard to indications for
      surgery and outcome. RESULTS: Over time the proportion of patients operated on
      because of testicular growth retardation increased. Persistence/recurrence rate
      was comparable between the two groups. In 13% of group B patients, the
      deferential vein was found to be refluxing on preoperative CDUS and was divided
      at surgery. Hydrocele rate was higher in group A, unless the vaginalis was
      excised and everted during varicocelectomy. About 75% of patients with
      preoperative left testicular growth failure experienced postoperative catch-up
      growth, irrespective of treatment. CONCLUSION: Indications for treatment are
      still evolving. Varicocele can successfully be treated in the majority of cases
      by either a laparoscopic or subinguinal approach. Both techniques require care,
      and CDUS can aid in the decision making. Most patients with preoperative
      testicular growth failure experience postoperative catch-up growth.

PMID- 18631905
TI  - Diagnostic accuracy of color Doppler sonographic study of the ureteric jets in
      evaluation of hydronephrosis.
AB  - OBJECTIVE: Hydronephrosis (HN) and obstruction are closely associated, but upper
      urinary tract dilatation can occur without significant obstruction. Despite some
      pitfalls, conventional ultrasonography and diuretic renography (DR) are the main
      means of evaluation of HN in children. Recent reports have demonstrated color
      Doppler ultrasonography (CDUS) to reliably identify ureteric jets in the bladder.
      The aim of this study was to evaluate this method as a diagnostic tool to
      distinguish obstructive from non-obstructive dilatations of the upper tract.
      METHODS: We evaluated 51 patients (37 boys and 14 girls), aged 3 months to 14
      years (median 4 years), who presented with unilateral grade III and IV
      hydronephrosis with suspicion of pyeloureteral junction obstruction. All patients
      underwent DR and evaluation of ureteric jets by transverse CDSG of the bladder
      within a maximum of 2 weeks. Obstruction was considered in the DR when the
      hydronephrotic unit showed a differential renal function of less than 40%, or
      when symptomatic intermittent renal colic was present in older children. The
      number of ureteric jets was counted over a 5-min period and the frequency
      calculated for each ureteral orifice. Relative jet frequency (RJF) was defined as
      frequency of the hydronephrotic side divided by total ureteric jet frequency.
      Receiver-operating characteristic (ROC) plots were constructed to determine the
      best cut-off for RJF, in order to identify renal units with obstructive
      hydronephrosis. RESULTS: Twenty-three (45.1%) hydronephrotic units were
      considered obstructed. The mean RJF differed between obstructive (0.09+/-0.15)
      and non-obstructive hydronephrosis (0.42+/-0.11) (p<0.001). ROC analysis revealed
      that RJF <0.25 was the best threshold, and correctly discriminated obstruction in
      91.2% of the children with a sensitivity of 87% (95% CI 78.6-98.2%) and
      specificity of 96.4% (95% CI 87.8-99%). The positive likelihood ratio was 24.3
      and the area under the ROC curve was 0.92 (95% CI 0.86-0.98). CONCLUSIONS: RJF
      <25% was found to be a good indicator of obstruction in children with unilateral
      hydronephrosis. CDUS evaluation of ureteric jets is an easy and non-invasive
      method that can be used as an initial diagnostic tool, and in follow-up cases, to
      differentiate obstructed from non-obstructed hydronephrosis in the pediatric
      population.

PMID- 18631906
TI  - Comparative efficacy and safety of extended-release and instant-release
      tolterodine in children with neural tube defects having cystometric
      abnormalities.
AB  - AIM: To evaluate the comparative efficacy and safety of extended-release (ER) and
      instant-release (IR) tolterodine preparations in a pediatric population with
      neural tube defects having cystometric abnormalities. MATERIALS AND METHODS:
      Twenty-five patients with neural tube defects and a similar demographic profile
      underwent a routine hemogram, liver function tests, renal function tests, urine
      culture, X-ray lumbo-sacral spine, and renal and bladder ultrasound.
      Vesicoureteric reflux was diagnosed by micturating cystourethrogram under
      fluoroscopy. Dimercaptosuccinic acid renal scintigraphy was performed to study
      the presence or absence of renal scars. Patients were treated with tolterodine ER
      (Group I: 2mg once daily for 21 days) and tolterodine IR (Group II: 2mg twice
      daily for 21 day) in a cross-over study with a 10-day washout period between
      administrations. Evaluation was by subjective assessment, visual analog scale,
      urodynamic assessment and adverse drug reaction monitoring. RESULTS: There was
      ultrasound evidence of hydroureteronephrosis in 20% of the patients. One patient
      out of 25 had impaired renal function and eight patients had renal scarring on
      dimercaptosuccinic acid scans. Both forms of the drug increased the maximum
      cystometric bladder capacity, decreased detrusor leak pressures and increased
      compliance compared to pre-therapy levels (P=0.0001). Visual analog scale showed
      a significant clinical improvement with both ER and IR tolterodine. A significant
      increase in maximum bladder capacity in the group receiving IR tolterodine as
      compared to the ER preparation was noted (P=0.0001). The decrease in detrusor
      leak pressures and improvement in compliance were not significantly different
      between the groups. No adverse effects of hyperpyrexia, flushing or intolerance
      to outdoor temperatures, or dryness of mouth were observed in either group. No
      patient suffered from constipation. CONCLUSION: ER tolterodine 2mg once daily is
      as effective and well tolerated in children with neurogenic bladder as IR
      tolterodine 2mg twice a day. The latter was found to be more effective in terms
      of urodynamic parameters. ER formulation of tolterodine is less expensive and has
      the advantage of single dosage.

PMID- 18631907
TI  - Total endoscopic management (TEM approach) of children with non-compliant
      neuropathic bladder: a preliminary report.
AB  - PURPOSE: We prospectively evaluated the efficacy and durability of a combination
      of intradetrusor botulinum-A toxin (BTX-A) and endoscopic treatment of
      vesicoureteric reflux (VUR) to manage children with myelomeningocele (MMC) and
      non-compliant refluxing bladders who were not responding to standard conservative
      therapy. We also evaluated whether this combined therapy can lower intravesical
      pressure, increase bladder capacity, gain social continence and protect the upper
      tract from recurrent urinary tract infection. MATERIAL AND METHODS: A total of 10
      patients with a mean age of 5.9+/-3.6 years (range 2-12 years) with MMC (eight
      females and two males) were prospectively involved in the study. All patients
      were fully compliant to clean intermittent catheterization, and all were non
      responders (failed to gain continence and/or poor compliance) to the maximum
      tolerable dose of anticholinergics and catheterization. All patients were
      subjected to cystoscopic intradetrusor injection of 12 U/kg (maximum 300 U) of
      BTX-A in an infection-free bladder. They all had VUR (16 refluxing ureters, six
      patients with bilateral VUR) and did not show resolution in the pretreatment
      voiding cystourethrogram; accordingly, submucosal injection of Deflux was
      performed either with the second BTX-A treatment (initial four patients) or with
      the first BTX-A treatment (the other six patients). The grade of reflux was G
      III, IV and V in three, seven and six ureters, respectively. RESULTS: The maximum
      bladder capacity increased significantly from 79+/-49 to 155+/-57 ml (p<0.022),
      and the maximum detrusor pressure decreased significantly from 55+/-16 to 37+/-11
      cm H(2)O (p<0.001). Fifteen out of 16 (93.75%) refluxing ureters were completely
      resolved (one of them on second attempt), and one (6.25%) (GV reflux) remained
      unchanged despite of two attempts. Of six incontinent patients, five reached
      complete dryness between catheterizations and one showed partial improvement.
      CONCLUSIONS: A combination of BTX-A and endoscopic correction of VUR is a simple
      and effective way to overcome the increased risk of high intravesical pressure
      and recurrent UTI. This treatment decreases the incidence of renal damage in
      children on whom conservative management fails to help, in a minimally invasive
      way.

PMID- 18631908
TI  - Quantifying demographic, urological and behavioral characteristics of children
      with lower urinary tract symptoms.
AB  - OBJECTIVE: This project examines the voiding and behavioral characteristics of
      children referred to a specialty voiding clinic, including the impact of
      incontinence on the child and family. PATIENTS AND METHODS: A total of 351 new
      patients (aged 5-17 years) referred to our specialty voiding clinic completed
      background information, including demographics and medical history, a
      standardized voiding questionnaire, school history, and questions about child and
      family quality of life, prior to their first appointment. RESULTS: Patients are
      primarily female (53%) and Caucasian (70%) with a mean age of 9.5 years (range 5
      17; SD=3.5). Of the patients, 25% were diagnosed with a mental or behavioral
      health problem. Mean urological symptom score was 12 (range 0-29). Higher symptom
      scores are associated with younger age, ethnic minority status, a mental health
      diagnosis, being on psychotropic medications, and a poor child and family quality
      of life. Families of children who are wet day and night reported a poorer quality
      of life as compared to the families of children who were daytime wetters or
      bedwetters only. CONCLUSION: Symptom scores are associated with type of
      incontinence, social and quality of life variables. Collecting this baseline data
      will enable ongoing monitoring of progress for these complex patients.

PMID- 18631909
TI  - Testicular tumors in children and adolescents.
AB  - OBJECTIVE: To analyze the spectrum of testicular tumors in children in an
      unselected population-based series, as well as the results of testis-preserving
      surgery. PATIENTS AND METHODS: Our hospital database was analyzed for operations
      for testicular tumors from 1981 to 2006. The clinical data and findings during
      follow up (4.7 years) were recorded. RESULTS: Thirty-four patients were operated
      on because of testicular tumors. In 23 (68%) the tumor was benign: benign
      teratoma (16), Leydig-cell tumor (2), epidermoid cyst (2), Sertoli-cell tumor
      (1), cystic dysplasia (1), intratesticular focal fibrosis (1). Eleven patients
      (32%) had a malignant tumor: yolk-sac tumor (6), embryonal carcinoma (5). Twenty
      out of the 26 (77%) prepubertal boys had a benign tumor in contrast to only three
      of the eight (38%) adolescent males (P=0.079). Testis-preserving surgery was
      performed in 10 patients. In eight, the tumor was curatively excised and
      remaining testis preserved. Two patients with benign teratoma had a recurrence
      due to incomplete primary resection. In one patient who underwent orchiectomy for
      benign teratoma, two metachronous teratomas were detected in the contralateral
      testis 6 years after primary surgery. CONCLUSIONS: In children, most testicular
      tumors are benign, especially before puberty. If testis-preserving surgery is
      contemplated, complete excision of the tumor should be ascertained. The
      possibility of metachronous bilateral tumors should be considered in the follow
      up of testicular teratomas.

PMID- 18631910
TI  - Lymphatic preservation using methylene blue dye during varicocele surgery: a
      single-center retrospective study.
AB  - OBJECTIVE: Hydrocele and testicular edema caused by division of lymphatic vessels
      during varicocelectomy could lead to decrease in testicular function. In-vivo
      methylene blue mapping of testicular lymphatic vessels should prevent damage to
      the lymphatic system. MATERIALS AND METHODS: We retrospectively compared outcomes
      for 46 patients who received an intraparenchymal injection of 0.25 ml of vital
      dye (isosulphan blue) before a laparoscopic or an inguinal/subinguinal spermatic
      vein ligation with 93 controls in whom no mapping technique was adopted. RESULTS:
      Methylene blue mapping of testicular lymphatics reduced the incidence of
      postvaricocelectomy hydrocele from 6.4% (6/93) to 2.1% (1/46); the incidence of
      hydrocele was 0% in all cases of successful lymphatic mapping. CONCLUSION:
      Mapping of testicular lymphatic drainage with intraparenchymal vital dye is an
      easy, safe, rapid and cost-free technique. We stress the importance of sparing
      the lymphatic system to ensure the best andrological outcome.

PMID- 18631911
TI  - A long-term prospective analysis of pediatric unilateral inguinal hernias: should
      laparoscopy or anything else influence the management of the contralateral side?
AB  - PURPOSE: To prospectively determine if children who present with a unilateral
      inguinal hernia can be identified as at risk for developing a metachronous
      inguinal hernia (MIH) based on risk factors and laparoscopic findings of the
      contralateral internal ring. MATERIALS AND METHODS: Between April 2000 and
      October 2004, 299 patients with a unilateral inguinal hernia were followed
      prospectively. Laparoscopy was attempted in each child. Bilateral repair was only
      performed in those with contralateral swelling or crepitus during laparoscopic
      evaluation. All other children were followed regardless of laparoscopic findings.
      Risk factors to include premature delivery, family history and increased
      abdominal pressure were recorded. Clinical follow up and annual phone interviews
      were performed to determine the development of a MIH. RESULTS: Thirteen patients
      underwent initial bilateral inguinal hernia repair. Of the remaining 286 patients
      (272 boys, 14 girls; ages 54+/-50.8 months), laparoscopy revealed 127 closed, 48
      cleft and 67 open (contralateral patent processus vaginalis) contralateral
      internal rings, and in 44 laparoscopy was not possible due to a small hernia. Of
      222 patients followed for 53.2 months (30.1-82.5 months), 15 (6.8%) developed a
      MIH. When comparing age, gender, laterality, laparoscopic findings, family
      history, premature birth and intra-abdominal pressure, only family history
      exhibited a significant risk for MIH (33% vs 7.7%). However, 16/21 children with
      a family history never developed a MIH, and 47/53 children with a contralateral
      patent processus vaginalis have yet to develop one. CONCLUSIONS: Risk factors and
      laparoscopic findings failed to predict the few children who would develop a MIH.
      The contralateral side should not be routinely explored by any methodology.

PMID- 18631912
TI  - Pneumovesicoscopic diverticulectomy in children and adolescents: is open surgery
      still indicated?
AB  - OBJECTIVES: Surgical treatment of a congenital bladder diverticulum is indicated
      in symptomatic children. Diverticulectomy can be performed by an open or a
      laparoscopic approach. We report our recent experience in using the
      pneumovesicoscopic approach for accomplishing vesical diverticulectomy. METHODS:
      We operated on three boys with a mean age of 11.6 years (10-14 years) during
      August 2006 to February 2007. In all children, a ureteric catheter was introduced
      first by cystoscopy followed by intravesical CO(2) insufflation at a pressure of
      12-15 mmHg. Three trocars were inserted under visual control in the bladder.
      Diverticulectomy was performed. The defect was closed by interrupted sutures.
      Bladder drainage was achieved using a urethral catheter for 2 days. RESULTS: The
      mean operative time was 133.3 min (100-180 min). Oral intake began after a mean
      of 5.3h (4-6h). Minimal blood loss was encountered. Non-steroidal analgesics were
      used only during the 1st day postoperatively with no need for morphine. All
      patients were discharged on the 2nd day postoperatively after removal of the
      urethral catheter and tube drain. The mean follow-up period was 5 months (3-6
      months). CONCLUSION: Pneumovesicoscopic diverticulectomy is a feasible procedure.
      It does not require a long learning curve, and is associated with shorter
      hospital stay and rapid recovery with good cosmetic aspect. Pneumovesicoscopy has
      the potential to be used in the treatment of other conditions such as
      vesicoureteral reflux, and may replace open surgery.

PMID- 18631913
TI  - The modern staged repair of bladder exstrophy in the female: a contemporary
      series.
AB  - OBJECTIVE: Many changes have occurred in the treatment of bladder exstrophy over
      the last few years and several repairs are now offered, but there is a lack of
      long-term follow-up data. The purpose of this study was to evaluate long-term
      outcomes in a select group of female patients in whom modern staged repair was
      undertaken. PATIENTS AND METHODS: From an institutionally approved database 41
      patients were identified. All had undergone primary bladder exstrophy closure in
      1988-2005, at a mean age of 2 months (range 4h to 3 months), with or without an
      osteotomy by a single surgeon, and all were followed up for a minimum of 5 years.
      Twelve patients underwent osteotomy at the time of primary closure. Eight had a
      classic transverse innominate and vertical iliac osteotomy, and four a transverse
      innominate only. Mean age at the time of bladder neck repair (BNR) was 4.2 years
      (39-65 months). Mean measured bladder capacity under gravity cystograms at the
      time of repair was 109 cc (80-179 cc). RESULTS: Thirty patients (74%) were
      continent day and night, and voiding per urethra without augmentation or
      intermittent catheterization. Social continence, defined as dry for more than 3h
      during the day but damp at night, was found in a further four cases (10%). Seven
      patients are completely incontinent with dry intervals of less than 1h day and
      night. The mean time to daytime continence was 12 months (4-16 months) and to
      night-time continence was 19 months (10-28 months). Patients with a mean capacity
      greater than 100 cc had better outcomes. Six of the 30 patients achieved dryness
      after primary closure only, and all six had transverse innominate and vertical
      iliac osteotomy at the time of primary closure. CONCLUSIONS: Female classic
      exstrophy patients with a good template who develop adequate capacity after a
      successful primary closure can achieve acceptable continence without bladder
      augmentation and intermittent catheterization. A select group will develop
      continence with closure alone without the need for bladder neck repair.

PMID- 18631914
TI  - Posterior urethral injury in male children: long-term follow up.
AB  - OBJECTIVE: Owing to the immature pelvis and the relative intra-abdominal position
      of the child's bladder, children with a posterior urethral injury differ from
      adults. We report our experience in the management of such injuries in male
      children. PATIENTS AND METHODS: Children with suspected urethral injury underwent
      retrograde urethrography once their clinical condition was stable. Children with
      complete urethral injury underwent primary urethral realignment either
      endoscopically or by open surgical technique. Suprapubic cystostomy was performed
      in other children who were unfit to undergo primary realignment or in whom the
      management of other injuries took precedence over that of urethral injury.
      Children referred from elsewhere for further management of urethral injury and
      those with initial suprapubic cystostomy underwent delayed urethroplasty.
      RESULTS: Twenty-two children with mean age of 11.3 years were treated at our
      centre for urethral injury. Seven children underwent primary endoscopic urethral
      realignment, five open surgical realignment and 10 initial suprapubic cystostomy
      followed by delayed urethroplasty. Six of the 12 children undergoing primary
      urethral realignment required additional endoscopic urethrotomy for managing the
      stricture, and three of these six children eventually underwent urethroplasty. Of
      the 10 children undergoing delayed urethroplasty, three required additional
      sessions of endoscopic urethrotomy and two of these required further correction
      graft urethroplasty. CONCLUSION: Most male children with posterior urethral
      injuries need immediate realignment to prevent long-term complications.

PMID- 18631915
TI  - Laparoscopic pyeloplasty: role of preoperative retrograde pyelography.
AB  - Laparoscopic dismembered pyeloplasty is a minimally invasive, safe and effective
      therapy for pelvi-ureteric junction obstruction with low morbidity, shorter
      convalescence and excellent outcomes. To maximize an efficacious outcome,
      minimally invasive treatment of this condition requires preoperative planning
      with adequate imaging, but the role of retrograde pyelography remains
      controversial. We present a report in which retrograde pyelography accurately
      contributed to the perioperative diagnosis of ureteral fibroepithelial polyps,
      subsequently altering surgical management.

PMID- 18631916
TI  - Graft-versus-host disease and phimosis.
AB  - Graft-versus-host disease rarely causes genitourinary problems. We report a case
      of pathological phimosis in a child secondary to chronic graft-versus-host
      disease.

PMID- 18631917
TI  - Ureteropelvic junction obstruction in both upper and lower moieties of a duplex
      system: a rare association.
AB  - Ureteropelvic junction (UPJ) obstruction is a rare association with duplex
      system. It has been reported infrequently in lower and upper pole moieties. This
      is the first case of both upper and lower moieties UPJ obstruction to be reported
      in the literature. This case adds one more variant to the known wide spectrum of
      duplex systems.

PMID- 18631918
TI  - A favorable outcome following 32 vesicocentesis and amnioinfusion procedures in a
      fetus with severe prune belly syndrome.
AB  - Patients with severe prune belly syndrome rarely survive beyond the first days of
      life. We present a case of prune belly syndrome that initially presented with
      severe oligohydramnios, megacystis and associated poor urine biochemistries. Due
      to an anteriorly located placenta the patient was referred to three major
      centers, but was turned down because of the unfavorable prognostic findings.
      Therefore, fetal intervention was performed with 32 vesicocentesis and
      amnioinfusion procedures. Despite the unfavorable prenatal findings, and having
      undergone numerous fetal interventions, the birth resulted in a viable infant.

PMID- 18631919
TI  - Diagnostic laparoscopy in a Gartner's duct cyst.
AB  - Gartner's duct cysts associated with renal dysgenesis are rare malformations and
      represent a diagnostic challenge. We report on one such case in which final
      diagnosis was achieved by laparoscopy and discuss the possible role of minimally
      invasive surgery in the management of this condition.

PMID- 18631920
TI  - Journal of Pediatric Urology. Editorial.

PMID- 18631921
TI  - Congenital hydrocele: prevalence and outcome among male children who underwent
      neonatal circumcision in Benin City, Nigeria.
AB  - OBJECTIVE: To determine the prevalence and spontaneous resolution of congenital
      hydrocele diagnosed in male neonates who underwent circumcision at our centre.
      PATIENTS AND METHODS: All male neonates presented for circumcision at the
      University of Benin Teaching Hospital, Benin City, Nigeria between January 2002
      and December 2006 were examined for the presence of hydrocele. Those diagnosed
      with this condition were recruited and followed up in a surgical outpatient
      clinic for 2 years. The number of cases of spontaneous resolution and age at
      which this occurred were documented on a structured pro forma. RESULTS: A total
      of 2715 neonates were circumcised and 128 (4.7%) were diagnosed with 163 cases of
      hydrocele, while 27 cases in 25 (0.9%) children failed to resolve at the age of 2
      years. Neonatal hydrocele was bilateral in 112 (68.7%), and there were 20 (12.3%)
      right and 31 (19.0%) left. Among those with hydrocele, 28.1% were delivered
      preterm and resolution was spontaneous in many of them, with no observed
      significant statistical difference to those delivered full term (P=0.4740). Of
      the 163 hydrocele cases, 136 (83.4%) resolved spontaneously by age 18 months with
      peak resolution at 4-6 months. No spontaneous resolution occurred after 18 months
      and no hydrocele-related complication occurred during follow up. CONCLUSION:
      Neonates with congenital hydrocele should be observed for spontaneous resolution
      for at least 18 months before being subjected to surgery.

PMID- 18631922
TI  - Ectopic ureteroceles in duplex systems: long-term follow up and 'treatment-free'
      status.
AB  - OBJECTIVE: Definitive treatment of ectopic ureterocele (EU) implies that no
      further surgery or prophylactic antibiotic is needed. The literature is unclear
      on which interventions render a child 'treatment free'. MATERIALS AND METHODS:
      Thirty (23 female, seven male) patients presented between 1984 and 2000. Follow
      up ranged from 5 to 15 years (mean: 7). Presenting reasons were: urinary tract
      infection in 18 (16 females, two males; age: 17<6 months, one 2 years), prenatal
      ultrasound in 11 (seven females, four males), and renal failure in one (male,
      aged 3 weeks). RESULTS: Treatment was as follows. No intervention, three (10%).
      Single procedure, eight (27%): five hemi-nephrectomy (HN), two transurethral
      incisions (TUI), one excision and re-implantation (E&R). Two procedures, 14
      (47%): first procedure 10 TUI, 4 HN; second procedure 13 E&R, 1 TUI. Three
      procedures, three (10%): first 2 TUI, 1 HN; second 3 TUI; third 2 E&R, 1 HN. Four
      procedures, two (7%): first 2 TUI; second 1 HN, 1 TUI; third 2 TUI; fourth 2 E&R.
      Eight (27%) remained on prophylaxis: two had no intervention, in 4 the ectopic
      ureterocele was in situ after HN or TUI, and two had reflux after E&R. Twenty two
      (73%) came off prophylaxis (16 E&R, 4 HN, 1 TUI, 1 observation). Poorly or non
      functioning upper pole moieties were left in place in 14/18 who underwent E&R.
      CONCLUSION: 'Treatment-free' status most often requires ureterocele excision. HN
      alone can be definitive, while TUI alone is so rarely. Poor or non-functioning
      upper pole segments can remain after E&R. Children with collapsed ureteroceles in
      situ often must remain on antibiotic prophylaxis. A staged approach with initial
      TUI, followed by E&R, was successful in definitively treating the majority.

PMID- 18631923
TI  - Long-term follow up of antenatally diagnosed megaureters.
AB  - AIM: We have retrospectively evaluated our 17 years of experience with antenatal
      diagnosis of hydronephrosis that led to postnatal diagnosis of megaureter, and
      tried to determine criteria for surgery. PATIENTS AND METHODS: Seventy-nine
      children (64 boys and 15 girls) with antenatal diagnosis of hydronephrosis that
      led to postnatal diagnosis of megaureter were followed conservatively over a
      period of 18 years (1988-2006). Right ureterohydronephrosis was seen in 23
      children, left in 30 and 26 had bilateral ureterohydronephrosis comprising a
      total of 105 renal units (RU). According to SFU (Society for Fetal Urology)
      classification, 8 RU were grade 1, 57 grade 2, 29 grade 3 and 11 grade 4
      postnatal hydronephrosis. Mean ureteral diameter was 1.2 cm. Relative renal
      function was in 82 RU more than 40%, in 18 RU 30-40% and in 5 RU less than 30%.
      Functional deterioration of the hydronephrotic kidney of more than 5%, worsening
      of hydronephrosis (SFU upgrade) and a persistent obstructive curve on
      radionuclide scans were the main indications for surgery. RESULTS: Twenty-five
      (31%) children required surgical correction. Mean age at surgery was 14.3 months
      (range 3-60). Univariate analysis revealed that gender and side of obstruction
      are not significant predictive factors for surgery SFU grade 3-4 of postnatal
      hydronephrosis, Relative renal function less than 30% and ureteral diameter more
      than 1.33 cm were significant independent risk factors leading to reimplantation.
      CONCLUSIONS: Only 30% of children with antenatal diagnosis of megaureter required
      surgical correction. Renal function less than 30%, grades 3 and 4 hydronephrosis,
      and ureteric diameter more than 1.33 cm are statistically significant and
      independent predictive factors for surgery.

PMID- 18631924
TI  - The role of laparoscopic surgery for urinary tract reconstruction in infants
      weighing less than 10 kg: a comparison with open surgery.
AB  - PURPOSE: To compare the outcome of laparoscopic urinary tract reconstruction
      (LUTR) in children weighing 10 kg or less with a weight-matched cohort undergoing
      open urinary tract reconstruction surgery (OUTR). MATERIALS AND METHODS: We
      conducted a retrospective chart review of patients weighing 10 kg or less at the
      time of surgery who underwent open or laparoscopic pyeloplasty, transuretero
      ureterostomy and ipsilateral uretero-ureterostomy between January 2000 and May
      2007. The following information was recorded: body weight, age, sex, diagnosis,
      type of procedure, operative time, estimated blood loss, pre- and postoperative
      hemoglobin levels, length of hospitalization, length of follow up, use of drains
      and stents, intraoperative and postoperative analgesic requirement, need for
      readmission, subsequent procedures, costs, complications and reoperations.
      RESULTS: There were 52 patients divided into two groups: LUTR (n=23) and OUTR
      (n=29). Median weight (range) and follow up was 6.2 kg (3.9-10) and 9 months and
      6.5 kg (4.7-9.6) and 31 months for LUTR and OUTR, respectively. Mean operative
      time for LUTR (including cystoscopy and stent placement) was 237 min and for OUTR
      128 min (P<0.01). There were no differences in blood loss, intra- or
      postoperative analgesic requirement, results or complications. Mean
      hospitalization time was shorter for LUTR than OUTR (2 and 3 days, respectively).
      There were no differences in hospital costs between the two groups. CONCLUSIONS:
      Laparoscopic reconstructive surgery for congenital urological anomalies is safe
      and effective in small infants and can be performed with outcomes comparable to
      that of open surgery.

PMID- 18631925
TI  - Symptoms of sleep-disordered breathing in children with nocturnal enuresis.
AB  - OBJECTIVES: There is an association between sleep-disordered breathing (SDB) and
      nocturia in adults, raising the question as to whether SDB could play a role in
      the aetiology of nocturnal enuresis (NE) in children. The aim of this study was
      to determine whether there is an association between these two conditions.
      METHODS: The study group comprised 40 patients, aged 5-15 years, with enuresis
      and the control group 40 children undergoing routine day-case surgery. Subjects
      completed a Pediatric Sleep Questionnaire (PSQ) and a questionnaire assessing
      lower tract symptoms. Categorical variables were analysed using Pearson's Xi(2)
      test, and group differences for continuous variables using Mann-Whitney and
      Kruskal-Wallis tests or t-tests according to the distribution of data. RESULTS:
      The groups were well matched. Patients with NE had significantly higher total PSQ
      scores (P<0.001). PSQ subscales relating to daytime sleepiness (P<0.003) and
      daytime behaviour (P<0.000) were significantly worse in NE patients. The snoring
      subscale was not statistically different (P<0.051), but a comparison of females
      alone showed a highly significant difference (P<0.001) with higher snoring
      subscale scores in girls with NE. CONCLUSION: Children with NE had significantly
      higher PSQ scores. The data suggest an association between NE and SDB in girls.
      The significantly higher level of reports of daytime sleepiness and behavioural
      problems in all NE children warrants further study to determine the potential
      causative pathways and clinical relevance of these findings. SDB could be
      usefully assessed in children with NE, particularly when they do not respond to
      standard treatment.

PMID- 18631926
TI  - Laparoscopic nephrectomy for xanthogranulomatous pyelonephritis in childhood: the
      way forward.
AB  - OBJECTIVE: Xanthogranulomatous pyelonephritis (XGP) is a severe, chronic renal
      parenchymal infection. Nephrectomy is curative. Open nephrectomy is a well-known
      operative challenge. We describe successful laparoscopic nephrectomy in three
      patients with XGP. MATERIALS AND METHODS: Case notes and radiology of three
      patients who underwent laparoscopic nephrectomy for XGP were reviewed. The
      preoperative presentation, operative details, postoperative recovery and
      complications were recorded. RESULTS: The ages of the three children were 9, 5
      and 1.3 years. Retroperitoneoscopy was performed via 3 x 5-mm ports. Creation of
      retroperitoneal space was easier than anticipated despite the perinephric
      inflammation. Excellent visualization of renal pedicle was obtained. The renal
      vessels were divided using the ultrasonic dissector (Sonosurg, Olympus). The
      kidney was then mobilized and dissected off adjacent structures. It was extracted
      via a small extension to one of the incisions on each occasion. None of them
      needed conversion. Average operating time was 3h and 30 min. Histology of XGP was
      confirmed in all. CONCLUSIONS: Laparoscopic nephrectomy has replaced open
      nephrectomy for most conditions. Preoperatively, it was thought that laparoscopy
      might be unsuitable because of the involvement of perinephric tissues commonly
      seen in this condition; however, excellent visualization was achieved enhancing
      the ease of dissection. Dealing with the pedicle before handling the kidney also
      proved beneficial, allowing better visualization and safe dissection.
      Postoperative pain and morbidity were greatly reduced. The cosmetic result was
      excellent. We recommend the laparoscopic approach for nephrectomy in XGP when
      expertise is available.

PMID- 18631927
TI  - Evaluation of the results of eccentric circummeatal-based flap with combined
      limited urethral mobilization technique for distal hypospadias repair.
AB  - OBJECTIVE: To evaluate the outcome of patients with distal hypospadias who are
      operated using the eccentric circummeatal-based flap (ECBF) with combined limited
      urethral mobilization (LUM) technique. PATIENTS AND METHODS: We retrospectively
      reviewed the medical records of all patients who underwent distal hypospadias
      repair at our institution between January 2000 and December 2005. Seventy-one
      patients with distal hypospadias were operated. Eighteen cases were operated with
      glanular approximation and 11 cases using the Snodgrass procedure. Forty-two
      cases of distal hypospadias without a thin distal urethra were operated using an
      eccentric circummeatal-based flap with combined limited urethral mobilization. We
      reviewed these 42 patients according to age at surgery, position of meatus,
      presence of ventral curvature or glanular tilt, previous operations, duration of
      catheterization and hospitalization, and early and late postoperative
      complications. RESULTS: The mean age at operation was 5.9+/-3.1 years. The
      position of the meatus was coronal in 29 patients (69%), glanular in seven
      (16.7%) and subcoronal in six (14.3%). Two patients had ventral curvature. Five
      patients had undergone previous unsuccessful hypospadias repair and five had
      undergone circumcision. The average length of catheterization was 4.64+/-1.07
      days. All patients were discharged after stent removal. At follow up of 1-31
      months (median 6 months, 22 patients over 6 months), three patients had a
      slightly glanular urethral meatus and six patients had a decrease in calibration
      during urination which responded to meatal dilatation. No fistula had occurred.
      All patients achieved a normally situated vertical slit-like glanular meatus.
      CONCLUSION: This technique is simple with satisfying cosmetic results, and can
      also be applied to patients who have undergone previous failed operations. The
      absence of fistula formation and short duration of hospital stay are additional
      advantages.

PMID- 18631928
TI  - Testicular torsion: orchiectomy or orchiopexy?
AB  - OBJECTIVE: To evaluate the impact on testicular function of the surgical approach
      used to treat testicular torsion. PATIENTS AND METHODS: Seventeen males operated
      on for testicular torsion at a median age of 14 years were investigated. Serum
      follicle-stimulating hormone (FSH), testosterone and inhibin B as well as
      testicular volume were measured early (median 36 days) and/or late (median 1.1
      years) after operation. RESULTS: Orchiectomy was performed in six, and testicular
      detorsion and orchiopexy in 11 patients. The duration of the preoperative
      symptoms in the detorsion group was 15 h (range 6-168) and in the orchiectomy
      group 42 h (range 24-96) (P=0.03). Preoperative colour Doppler ultrasonography
      showed some circulation in 40% of the patients. At 1 month the median serum
      inhibin B level was significantly higher after preserving surgery (P=0.01). At 1
      year postoperatively, the median serum FSH level tended to be lower after
      testicular preservation (P=0.09). Abnormal inhibin B or FSH values were observed
      in 35% of the patients. CONCLUSIONS: Testicular function is often compromised in
      patients with testicular torsion. Testis-preserving surgery yields better
      testicular function than orchiectomy in the short term if the testis is not
      obviously necrotic. Testicular torsion does not necessarily cause the circulation
      to cease completely, and preserving surgery can also sometimes be attempted after
      delayed diagnosis.

PMID- 18631929
TI  - Diagnostic laparoscopy and management of the impalpable testis--a review of 10
      years' practice at a non-paediatric specialist centre.
AB  - BACKGROUND: Laparoscopy is used for the diagnosis and treatment of impalpable
      testes. We reviewed practice and outcomes in our unit over the last 10 years.
      METHODS: Retrospective case-note review of patients undergoing laparoscopy with
      or without orchidopexy for impalpable testes. RESULTS: Eighty-three patients
      underwent laparoscopy. Twelve patients had bilateral impalpable testes; 25.3% of
      testes were identified intra-abdominally, 21% in the internal ring, and 29.5% of
      cases had vas and vessels entering the deep ring. A 76.5% success rate was
      achieved following diagnostic laparoscopy and standard open orchidopexy for
      testes in the region of the internal ring, compared to a 40.0% success rate
      following one-stage laparoscopic orchidopexy for 'low' intra-abdominal testes.
      CONCLUSION: Laparoscopy is useful in managing patients with an impalpable testis
      from both a diagnostic and therapeutic standpoint. The success rate following
      laparoscopic orchidopexy in our non-paediatric specialist centre is lower than in
      most reports from paediatric specialist centres. This suggests the importance of
      centralization of such complicated, less frequently performed surgical procedures
      to a specialist centre.

PMID- 18631930
TI  - Definitive identification of a patent processus vaginalis by intraoperative
      injection of methylene blue into the hydrocoele sac.
AB  - OBJECTIVE: Seven percent of patent processus vaginalis (PPVs) are obliterated at
      exploration. This potentially increases the risk of cord injury with a subsequent
      increased risk of testicular atrophy or reduced fertility. We report a
      modification of a technique to improve identification of the PPV and thus
      potentially minimise the risk to the cord. METHODS: Fifteen consecutive boys were
      operated on via a standard inguinal approach. The testicle was delivered and 0.2
      0.5 ml of a 50% methylene blue/normal saline solution was injected into the
      hydrocoele sac. A PPV is identified as a blue line. RESULTS: Methylene blue
      injection identified all PPV. In a case with an encrusted hydrocoele of the cord
      and a hydrocoele this anatomy was clearly delineated. Dissection in a recurrent
      case was better facilitated. No testicular atrophy was recorded and there were no
      significant complications. CONCLUSIONS: Intraoperative injection of a methylene
      blue solution into a hydrocoele sac will aid identification of a difficult PPV,
      thus minimising the risk of cord damage. This is especially helpful in cases of
      recurrent hydrocoele.

PMID- 18631931
TI  - Endoscopic treatment of vesicoureteral reflux using dextranomer hyaluronic acid
      copolymer.
AB  - Vesicoureteral reflux (VUR) is a common urinary tract anomaly. Treatment is
      performed to minimize the risk of febrile urinary UTIs that may result in renal
      scarring. The endoscopic use of dextranomer hyaluronic acid copolymer has been
      gaining popularity as an alternative to the traditional methods of open surgery
      and chronic antibiotic prophylaxis. The aim of this educational review was to
      present the trends, latest perspectives and surgical techniques regarding this
      newer method of treatment of VUR. Evolving techniques are described that have
      resulted in VUR cure rates that rival that of open ureteral reimplantation with
      minimal associated morbidity. These have proven to be effective in complex cases
      that were previously considered as contraindications for endoscopic treatment,
      including voiding dysfunction, duplex ureters, high-grade VUR and paraureteral
      diverticuli. It is recommended that open reimplantation be reserved for those
      children with ectopic ureters, megaureters that require tapering or secondary
      grade V VUR, and those who have failed two endoscopic injections. Future advances
      promise to standardize the injection technique, ensuring optimum needle placement
      for consistently successful injections.

PMID- 18631933
TI  - Fatal hyponatremia in a 7-year-old girl with cloacal exstrophy after cystoscopy
      for a bladder stone.
AB  - A case of fatal hyponatremia in a 7-year-old girl following a percutaneous
      cystolithotomy is presented. Stone removal by percutaneous cystolithotomy is
      considered a safe and effective procedure, but this may depend on the type of
      solution used for irrigation. In this case less than 2L of sterile water was used
      as irrigation in an augmented bladder causing a drop in sodium to 120 mmol/L in
      30 min. The result was a massive shift of water into the cerebral tissue,
      cerebral edema and death.

PMID- 18631934
TI  - Adenocarcinoma at the ureterosigmoidostomy site in a 16-year-old demonstrates the
      importance of screening in children.
AB  - We report the death of a 17-year-old male exstrophy patient from adenocarcinoma
      arising at the ureterosigmoidostomy. This was detected at reconstructive surgery
      at the age of 16 years, 13 years after ureterosigmoidostomy. This case highlights
      the importance of including children in endoscopic surveillance. We recommend
      annual sigmoid-colonoscopy commencing 10 years after ureterosigmoidostomy
      irrespective of age.

PMID- 18631935
TI  - Massive hematuria due to portal hypertension in a child with bladder augmentation
      for vesical exstrophy.
AB  - We report a case of a 17-year-old patient with severe hematuria from an
      ileocystoplasty-augmented bladder for vesical exstrophy, with associated
      cirrhosis secondary to autoimmune hepatitis, diagnosed years later. Varix
      development and further bleeding from ectopic varices, related to cirrhosis and
      portal hypertension, are a rare cause of hematuria in patients with surgically
      augmented bladder volume. This child was successfully treated with a transjugular
      intrahepatic portosystemic shunt procedure as a bridge to hepatic
      transplantation.

PMID- 18631936
TI  - Cutaneous calicostomy for salvage urinary diversion.
AB  - OBJECTIVE: We describe a salvage technique for urinary diversion in the face of
      an obstructed, undilated upper urinary tract utilized in the management of a
      premature newborn infant with bilateral renal candidiasis, namely cutaneous
      calicostomy. METHODS: An 850-g 24 weeks' gestation premature male infant
      developed obstructive nephropathy as a result of renal candidiasis. Systemic
      therapy with bilateral nephrostomy drainage and amphotericin B irrigations was
      repeatedly unsuccessful in eradicating the candiduria and fungal balls.
      Underlying bilateral proximal collecting system obstructions complicated the
      situation by rendering ureterostomy or pyelostomy impossible. Subsequent flank
      exploration was performed bilaterally, and bilateral cutaneous calicostomies were
      performed. RESULTS: The patient's urinary tract was successfully diverted and the
      fungal balls eradicated. Renal ultrasounds and antegrade nephrostograms through
      the cutaneous calicostomy stomas revealed the procedure to be successful.
      Unfortunately, the patient eventually died from overwhelming non-urologic sepsis
      approximately 3 months postoperatively. CONCLUSIONS: Although systemic antifungal
      therapy with bilateral nephrostomy drainage has been shown to be successful in
      the treatment of obstructive uropathy due to renal candidiasis, surgical
      intervention is necessary when recurrent sepsis with candiduria persists. In the
      event that underlying collecting system obstruction is also present, cutaneous
      calicostomy is an option to consider in the treatment of this disease.

PMID- 18631937
TI  - A rare cause of acute urinary retention in a male infant.
AB  - Acute urinary retention is an uncommon entity in childhood, and is associated
      with a variety of causes. Congenital bladder diverticulae are a rare cause of
      this condition, and occur almost exclusively in boys. True congenital
      diverticulae are most often solitary. Acute urinary retention is an extremely
      rare complication of congenital bladder diverticulae. Voiding cystourethrography
      is considered the most reliable method for detection. We report a case of a 3
      month-old male infant who was presented with several episodes of acute urinary
      retention caused by bilateral congenital bladder diverticulae. Clinical and
      radiological evaluation and surgical correction are discussed.

PMID- 18631938
TI  - Total laparoscopic correction of transverse testicular ectopia.
AB  - Transverse testicular ectopia is a well-described, rare congenital abnormality of
      testicular maldescent, in which both testes descend through one inguinal canal.
      There have been few reports on the laparoscopic diagnosis and laparoscopy
      assisted management of this condition. We present a case of a 5-year-old boy who
      underwent laparoscopy for a right impalpable testis. During the procedure, the
      right testis was identified at the left internal ring. The common investing meso
      orchium was divided and the right testis was brought down through the right
      inguinal canal laparoscopically. As far as we are aware, this is the first case
      of transverse testicular ectopia managed entirely laparoscopically.

PMID- 18631939
TI  - Retrieval of DJ stent by using ureteroscope in an infant.

PMID- 18631940
TI  - Comment on: Comparison of traditional enterocystoplasty and seromuscular
      colocystoplasty lined with urothelium, by G. Bandi, O. Al-Omar, G.A. McLorie.

PMID- 18631941
TI  - Abstracts of the XIXth Annual ESPU (European Society of Pediatric Urology)
      Conference. April 24-26, 2008. Nice, France.

PMID- 18631944
TI  - Exploring human/animal intersections: converging lines of evidence in comparative
      models of aging.
AB  - At a symposium convened on March 8, 2007 by the Institute on Aging at the
      University of Pennsylvania, researchers from the University's Schools of Medicine
      and Veterinary Medicine explored the convergence of aging research emerging from
      the two schools. Studies in human patients, animal models, and companion animals
      have revealed different but complementary aspects of the aging process, ranging
      from fundamental biologic aspects of aging to the treatment of age-related
      diseases, both experimentally and in clinical practice. Participants concluded
      that neither animal nor human research alone will provide answers to most
      questions about the aging process. Instead, an optimal translational research
      model supports a bidirectional flow of information from animal models to clinical
      research.

PMID- 18631946
TI  - Practicality of a computerized system for cognitive assessment in the elderly.
AB  - BACKGROUND: Early detection and diagnosis are critical to dementia care. However,
      many early cases remain undiagnosed as a result of the impracticality of
      neuropsychological testing, particularly in primary care. Mindstreams is an
      office-based computerized system for measuring cognitive function in multiple
      domains, with demonstrated validity, test-retest reliability, and sensitivity to
      treatment effects. This study evaluated its feasibility for assessment of the
      elderly. METHODS: Usability data were collected after each of 2,888 consecutive
      initial-visit testing sessions at the first 11 clinical centers to use
      Mindstreams. The chi(2) goodness-of-fit test was employed to determine whether
      patients and supervisors more often rated tests easy versus hard to use. Separate
      analyses were run for non-computer users, patients older than 75 years, and poor
      performers (< or =1 standard deviation on overall battery performance). RESULTS:
      For all patients (n = 2,888; age, 64.7 +/- 18.2 years), 83% rated the tests easy
      to use (P < .001). Seventy-three percent of non-computer users, 70% of patients
      older than 75, and 69% of poor performers rated them easy to use (Ps < .001).
      Supervisor ratings and ease of understandability ratings were similar. For all
      patients, 76% of supervisor ratings indicated no patient frustration (P < .001).
      Seventy-eight percent of ratings for non-computer users, 76% for patients older
      than 75, and 74% for poor performers indicated no frustration (Ps < .001).
      CONCLUSIONS: Mindstreams was easily employed, including in patients with
      considerable cognitive impairment, supporting its practicality for in-office
      cognitive assessment of the elderly. The availability of such valid and practical
      assessment suggests the feasibility of integrating the technology within a
      clinical algorithm for improved detection of cognitive decline.

PMID- 18631945
TI  - Elevated microsomal prostaglandin-E synthase-1 in Alzheimer's disease.
AB  - BACKGROUND: The proinflammatory prostaglandin E(2) (PGE(2)) fluctuates over time
      in the cerebrospinal fluid of patients with Alzheimer's disease (AD), but the
      cerebral distribution and expression patterns of microsomal prostaglandin-E
      synthase (mPGES)-1 have not been compared with those of normal human brains.
      METHODS: Middle frontal gyrus tissue from AD and age-matched control brains was
      analyzed by Western blot, immunofluorescence, and immunohistochemistry with mPGES
      1-specific antibodies. RESULTS: Western blotting revealed that mPGES-1 expression
      was significantly elevated in AD tissue. Furthermore, immunofluorescence of mPGES
      1 was observed in neurons, microglia, and endothelial cells of control and AD
      tissue. Although mPGES-1 was consistently present in astrocytes of control
      tissue, it was present in only some astrocytes of AD tissue. Immunohistochemical
      staining suggested that mPGES-1 was elevated in pyramidal neurons of AD tissue
      when compared with controls. CONCLUSIONS: The results suggest that mPGES-1 is
      normally expressed constitutively in human neurons, microglia, astrocytes, and
      endothelial cells but is up-regulated in AD.

PMID- 18631947
TI  - Prognosis of Alzheimer's disease today: a two-year prospective study in 686
      patients from the REAL-FR Study.
AB  - BACKGROUND: The aim of the present study was to describe the long-term evolution
      of Alzheimer's disease (AD) in a prospective cohort of patients under treatment
      with a close follow-up. METHODS: Six hundred eighty-six AD patients from the
      French Network on AD (REAL-FR) were followed up and assessed every 6 months for 2
      years. Cognitive, functional, behavioral, nutritional, and global status were
      evaluated by using Mini-Mental State Examination (MMSE), cognitive subscale of AD
      Assessment Scale (ADAS-cog), Activities of Daily Living scale (ADL),
      Neuropsychiatric Inventory (NPI), Mini-Nutritional Assessment (MNA), and Clinical
      Dementia Rating (CDR). RESULTS: There were 85.13% of patients who were
      specifically treated for AD during their participation in the study. We observed
      significant changes (P < .0001) on MMSE, -4.57 +/- 0.23; ADAS-cog, 7.11 +/- 0.41;
      ADL, -1.32 +/- 0.07; NPI, 2.94 +/- 0.77; MNA, -0.81 +/- 0.17; and sum of boxes of
      the CDR (CDR-SB), 4.17 +/- 0.17. After 2 years, 10.79% (95% confidence interval
      [CI], 8.47 to 13.11) of the patients evolved twice as rapidly as the mean of the
      whole cohort on MMSE (loss, > or =9 points), 65.89% (95% CI, 62.34 to 69.44)
      reported a loss of 3 to 9 points, and 23.32% (95% CI, 20.16 to 26.46) were stable
      or improved (loss of -2 points maximum). Annual incidences for
      institutionalization, hospitalization, and death were 11.84% (95% CI, 9.76 to
      13.92), 26.13% (95% CI, 22.52 to 29.74), and 5.95% (95% CI, 4.56 to 7.34),
      respectively. CONCLUSIONS: In a recent large AD cohort mostly under treatment, AD
      evolution appeared to be variable, with high incidences for death or
      institutionalization and with 11.84% of the patients exhibiting a rapid cognitive
      decline, whereas one fourth of the cohort appeared in relatively stable
      condition, and two thirds had a moderate but significant evolution of the
      disease. More studies are needed to better understand these variations in
      patients' evolution.

PMID- 18631948
TI  - One-week dose titration of extended release galantamine in patients with
      Alzheimer's disease.
AB  - BACKGROUND: Our purpose was to assess the safety and tolerability of extended
      release galantamine (GAL-ER), using a 1-week dose titration in Alzheimer's
      patients. METHODS: An open-label, 12-week, multicenter study was performed (n =
      82). Results were compared with findings from a placebo-controlled trial using a
      4-week titration of GAL-ER and immediate-release galantamine. The primary
      analysis compared incidences of adverse events (AEs). RESULTS: Although not
      statistically significant, more patients in the 1-week titration study
      experienced an AE. More patients with a 1-week titration had at least one
      prespecified gastrointestinal (GI) AE. These findings correlated with a higher
      baseline incidence of GI disturbances. Four patients experienced serious AEs; no
      deaths occurred. Mean Mini-Mental State Examination scores improved by 1.8 and
      1.9 points at weeks 4 and 12, respectively. CONCLUSIONS: A 1-week titration of
      GAL-ER was generally safe and well tolerated, with a potential risk of more GI
      side effects. A 1-week titration may permit dosing flexibility and promote
      increased adherence to medication regimens.

PMID- 18631949
TI  - Core candidate neurochemical and imaging biomarkers of Alzheimer's disease.
AB  - BACKGROUND: In the earliest clinical stages of Alzheimer's disease (AD) when
      symptoms are mild, clinical diagnosis can be difficult. AD pathology most likely
      precedes symptoms. Biomarkers can serve as early diagnostic indicators or as
      markers of preclinical pathologic change. Candidate biomarkers derived from
      structural and functional neuroimaging and those measured in cerebrospinal fluid
      (CSF) and plasma show the greatest promise. Unbiased exploratory approaches, eg,
      proteomics or cortical thickness analysis, could yield novel biomarkers. The
      objective of this article was to review recent progress in selected imaging and
      neurochemical biomarkers for early diagnosis, classification, progression, and
      prediction of AD. METHODS: We performed a survey of recent research, focusing on
      core biomarker candidates in AD. RESULTS: A number of in vivo neurochemistry and
      neuroimaging techniques, which can reliably assess aspects of physiology,
      pathology, chemistry, and neuroanatomy, hold promise as biomarkers. These
      neurobiologic measures appear to relate closely to pathophysiologic,
      neuropathologic, and clinical data, such as hyperphosphorylation of tau, amyloid
      beta (Abeta) metabolism, lipid peroxidation, pattern and rate of atrophy, loss of
      neuronal integrity, functional and cognitive decline, as well as risk of future
      decline. Current advances in the neuroimaging of mediotemporal, neocortical, and
      subcortical areas of the brain of mild cognitive impairment (MCI) and AD subjects
      are presented. CSF levels of Abeta42, tau, and hyperphosphorylated tau protein (p
      tau) can distinguish subjects with MCI who are likely to progress to AD. They
      also show preclinical alterations that predict later development of early AD
      symptoms. Studies on plasma Abeta are not entirely consistent, but recent
      findings suggest that decreased plasma Abeta42 relative to Abeta40 might increase
      the risk of AD. Increased production of Abeta in aging is suggested by elevation
      of BACE1 protein and enzyme activity in the brain and CSF of subjects with MCI.
      CSF tau and p-tau are increased in MCI as well and show predictive value. Other
      biomarkers might indicate components of a cascade initiated by Abeta, such as
      oxidative stress or inflammation. These merit further study in MCI and earlier.
      CONCLUSIONS: A number of neuroimaging candidate markers are promising, such as
      hippocampus and entorhinal cortex volumes, basal forebrain nuclei, cortical
      thickness, deformation-based and voxel-based morphometry, structural and
      effective connectivity by using diffusion tensor imaging, tractography, and
      functional magnetic resonance imaging. CSF Abeta42, BACE1, total tau, and p-tau
      are substantially altered in MCI and clinical AD. Other interesting novel marker
      candidates derived from blood are being currently proposed (phase I). Biomarker
      discovery through proteomic approaches requires further research. Large-scale
      international controlled multicenter trials (such as the U.S., European,
      Australian, and Japanese Alzheimer's Disease Neuroimaging Initiative and the
      German Dementia Network) are engaged in phase III development of the core
      feasible imaging and CSF biomarker candidates in AD. Biomarkers are in the
      process of implementation as primary outcome variables into regulatory guideline
      documents regarding study design and approval for compounds claiming disease
      modification.

PMID- 18631950
TI  - Behavioral effects of current Alzheimer's disease treatments: a descriptive
      review.
AB  - BACKGROUND: Behavioral abnormalities and neuropsychiatric symptoms are common
      manifestations of Alzheimer's disease (AD). Many clinical trials of
      cholinesterase inhibitors (ChE-Is) and memantine have included behavioral
      measures as primary or secondary outcomes, and most have observed behavioral
      benefits in conjunction with treatment. The purpose of this review was to
      determine the frequency of positive behavioral outcomes in AD clinical trials and
      clinical reports, to determine the symptoms most responsive to antidementia
      agents, and to explore factors that correlate with negative outcomes in clinical
      trials of antidementia agents with regard to behavioral measures. METHODS: We
      performed a computerized search of randomized clinical trials and open-label
      studies of ChE-Is and memantine for AD including a behavioral outcome measure.
      Studies involving 10 or more patients using therapeutic doses of the target
      agents and including a behavioral measure as a primary or secondary outcome were
      included in this review. RESULTS: One hundred fifty-seven peer-reviewed articles
      and 68 publicly presented abstracts were identified in the literature search.
      Subsequent review established that 15 publications arising from 13 randomized,
      double-blind, placebo-controlled AD trials met the review inclusion criteria.
      Positive outcomes on behavioral measures were reported in 8 of 15 publications as
      a primary or secondary outcome. In most blinded AD clinical trials, behavioral
      measures were secondary outcomes. Mood symptoms and apathy have most commonly
      responded to ChE-Is, whereas memantine has been associated with a reduction in
      irritability and agitation. However, there is substantial variability among
      trials in terms of behavioral outcomes. Studies that assessed patients with more
      severe dementia, included patients with less severe behavioral disturbances at
      baseline, involved institutionalized patients, or were international in scope
      tended to have negative outcomes. In institutionalized patients there is commonly
      an improvement in the placebo group that confounds the observation of any drug
      placebo difference. CONCLUSIONS: Antidementia agents have been associated with
      beneficial behavioral outcomes in many randomized clinical trials and open-label
      studies. Most studies are not designed to test the psychotropic properties of
      antidementia drugs. Trials with negative behavioral outcomes are most likely to
      involve patients who are institutionalized and have few behavioral disturbances
      at baseline. Clinical trials designed to assess behavioral effects of
      antidementia agents should anticipate these factors.

PMID- 18631951
TI  - Disease-modifying therapies in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic, progressive, neurodegenerative disorder
      that places a substantial burden on patients, their families, and society. The
      disease affects approximately 5 million individuals in the United States, with an
      annual cost of care greater than $100 billion. During the past dozen years,
      several agents have been approved that enhance cognition and global function of
      AD patients, and recent advances in understanding AD pathogenesis has led to the
      development of numerous compounds that might modify the disease process. A wide
      array of antiamyloid and neuroprotective therapeutic approaches are under
      investigation on the basis of the hypothesis that amyloid beta (A beta) protein
      plays a pivotal role in disease onset and progression and that secondary
      consequences of A beta generation and deposition, including tau
      hyperphosphorylation and neurofibrillary tangle formation, oxidation,
      inflammation, and excitotoxicity, contribute to the disease process.
      Interventions in these processes with agents that reduce amyloid production,
      limit aggregation, or increase removal might block the cascade of events
      comprising AD pathogenesis. Reducing tau hyperphosphorylation, limiting oxidation
      and excitotoxicity, and controlling inflammation might be beneficial disease
      modifying strategies. Potentially neuroprotective and restorative treatments such
      as neurotrophins, neurotrophic factor enhancers, and stem cell-related approaches
      are also under investigation.

PMID- 18631952
TI  - Partnership between academia and industry for drug discovery in Alzheimer's
      disease.
AB  - Drug discovery has traditionally been almost exclusively the purview of
      pharmaceutical and biotechnology companies, whereas universities have focused on
      basic research. However, given the challenges involved in discovering and
      developing truly effective, symptomatic treatments and disease-modifying drugs
      for Alzheimer's disease, there is a need to reassess this simple division of
      labor. Whereas each sector is likely to retain a core interest and expertise at
      either end of the drug discovery spectrum, there is room for closer cooperation
      at the intersection of the for-profit and not-for-profit sectors. The Alzheimer's
      Association Research Roundtable convened a meeting of senior industry researchers
      and academic investigators to discuss this intersection and to assess the
      opportunity for closer partnership on Alzheimer's disease drug discovery and
      development.

PMID- 18631953
TI  - New directions for frontotemporal dementia drug discovery.
AB  - This report summarizes the recommendations of the Frontotemporal Dementia (FTD)
      Working Group on FTD Drug Discovery that was part of an international FTD
      Workshop held on January 18 and 19, 2007, in Miami, Florida. The workshop was
      sponsored by the National Institute of Neurological Disorders and Stroke (NINDS)
      and the National Institute on Aging (NIA) of the National Institutes of Health
      (NIH) and the Association for Frontotemporal Dementia (AFTD) with the express
      purpose of defining opportunities to improve the diagnosis and treatment of
      patients affected by a neurodegenerative disorder classified as one of the many
      variants of FTD. The recognition that almost all forms of FTD are due to TDP-43
      proteinopathies and tauopathies creates new opportunities for FTD drug discovery
      targeting pathways of TDP-43 and tau-mediated neurodegeneration.

PMID- 18631954
TI  - Commentary on "New directions for frontotemporal dementia drug discovery." Do we
      know enough to develop meaningful treatments for frontotemporal dementia?

PMID- 18631956
TI  - 2008 Alzheimer's disease facts and figures.
AB  - Alzheimer's disease is the seventh leading cause of all deaths in the United
      States and the fifth leading cause of death in Americans older than the age of 65
      years. More than 5 million Americans are estimated to have Alzheimer's disease.
      Every 71 seconds someone in America develops Alzheimer's disease; by 2050 it is
      expected to occur every 33 seconds. During the coming decades, baby boomers are
      projected to add 10 million people to these numbers. By 2050, the incidence of
      Alzheimer's disease is expected to approach nearly a million people per year,
      with a total estimated prevalence of 11 to 16 million persons. Significant cost
      implications related to Alzheimer's disease and other dementias include an
      estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (eg,
      caregiver lost wages and out-of-pocket expenses, decreased business productivity)
      costs. Not included in these figures are the estimated 10 million caregivers who
      annually provide $89 billion in unpaid services to individuals with Alzheimer's
      disease. This report provides information to increase understanding of the public
      health impact of Alzheimer's disease, including incidence and prevalence,
      mortality, lifetime risks, costs, and impact on family caregivers.

PMID- 18631955
TI  - Consortium to Establish a Registry for Alzheimer's Disease (CERAD): the first
      twenty years.
AB  - The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was funded
      by the National Institute on Aging in 1986 to develop standardized, validated
      measures for the assessment of Alzheimer's disease (AD). The present report
      describes the measures that CERAD developed during its first decade and their
      continued use in their original and translated forms. These measures include
      clinical, neuropsychological, neuropathologic, and behavioral assessments of AD
      and also assessment of family history and parkinsonism in AD. An approach to
      evaluating neuroimages did not meet the standards desired. Further evaluations
      that could not be completed because of lack of funding (but where some materials
      are available) include evaluation of very severe AD and of service use and need
      by patient and caregiver. The information that was developed in the U.S. and
      abroad permits standardized assessment of AD in clinical practice, facilitates
      epidemiologic studies, and provides information valuable for individual and
      public health planning. CERAD materials and data remain available for those
      wishing to use them.

PMID- 18631957
TI  - Trends in the prevalence and mortality of cognitive impairment in the United
      States: is there evidence of a compression of cognitive morbidity?
AB  - BACKGROUND: Recent medical, demographic, and social trends might have had an
      important impact on the cognitive health of older adults. To assess the impact of
      these multiple trends, we compared the prevalence and 2-year mortality of
      cognitive impairment (CI) consistent with dementia in the United States in 1993
      to 1995 and 2002 to 2004. METHODS: We used data from the Health and Retirement
      Study (HRS), a nationally representative population-based longitudinal survey of
      U.S. adults. Individuals aged 70 years or older from the 1993 (N = 7,406) and
      2002 (N = 7,104) waves of the HRS were included. CI was determined by using a 35
      point cognitive scale for self-respondents and assessments of memory and judgment
      for respondents represented by a proxy. Mortality was ascertained with HRS data
      verified by the National Death Index. RESULTS: In 1993, 12.2% of those aged 70 or
      older had CI compared with 8.7% in 2002 (P < .001). CI was associated with a
      significantly higher risk of 2-year mortality in both years. The risk of death
      for those with moderate/severe CI was greater in 2002 compared with 1993
      (unadjusted hazard ratio, 4.12 in 2002 vs 3.36 in 1993; P = .08; age- and sex
      adjusted hazard ratio, 3.11 in 2002 vs 2.53 in 1993; P = .09). Education was
      protective against CI, but among those with CI, more education was associated
      with higher 2-year mortality. CONCLUSIONS: These findings support the hypothesis
      of a compression of cognitive morbidity between 1993 and 2004, with fewer older
      Americans reaching a threshold of significant CI and a more rapid decline to
      death among those who did. Societal investment in building and maintaining
      cognitive reserve through formal education in childhood and continued cognitive
      stimulation during work and leisure in adulthood might help limit the burden of
      dementia among the growing number of older adults worldwide.

PMID- 18631959
TI  - New thinking about thinking.

PMID- 18631958
TI  - The Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe): design and
      baseline characteristics.
AB  - BACKGROUND: Growing evidence suggests that elevated cholesterol levels in mid
      life are associated with increased risk of developing Alzheimer's disease (AD),
      and that statins might have a protective effect against AD and dementia. The
      Lipitor's Effect in Alzheimer's Dementia (LEADe) study tests the hypothesis that
      a statin (atorvastatin 80 mg daily) will provide a benefit on the course of mild
      to moderate AD in patients receiving background therapy of a cholinesterase
      inhibitor (donepezil 10 mg daily). METHODS: This is an international,
      multicenter, double-blind, randomized, parallel-group study with a double-blind
      randomized withdrawal phase of patients with mild to moderate AD (Mini-Mental
      State Examination [MMSE] score, 13 to 25). Inclusion criteria included age 50 to
      90 years, receiving donepezil 10 mg for at least 3 months before randomization,
      and low-density lipoprotein cholesterol levels (LDL-C) 2.5 to 3.5 mmol/L (95 to
      195 mg/dL). Co-primary end points are changes in AD Assessment Scale-cognitive
      subscale (ADAS-cog) and AD Cooperative Study-Clinical Global Impression of Change
      (ADCS-CGIC) scale scores. A confirmatory end point is rate of change in whole
      brain and hippocampal volumes in patients who enrolled in the magnetic resonance
      imaging substudy. RESULTS: Enrollment of 641 subjects is complete. The baseline
      mean data are age 74 +/- 8 years, 53% women, MMSE 22 +/- 3, ADAS-cog 23 +/- 10,
      AD Functional Assessment and Change Scale (ADFACS) 13 +/- 9, Neuropsychiatric
      Inventory (NPI) 10 +/- 11, and Clinical Dementia Rating-Sum of Boxes (CDR-SB) 6
      +/- 3. Mean prior donepezil treatment was 409 +/- 407 days. Mean baseline lipid
      levels are total cholesterol 5.8 +/- 0.8 mmol/L (224 +/- 33 mg/dL), LDL-C 3.7 +/-
      0.7 mmol/L (143 +/- 26 mg/dL), triglycerides 1.5 +/- 0.7 mmol/L (132 +/- 64
      mg/dL), and high-density lipoprotein cholesterol 1.6 +/- 0.5 mmol/L (64 +/- 18
      mg/dL). CONCLUSIONS: LEADe will report in 2008 and is expected to provide a more
      definitive evaluation of the potential for statins in the treatment of people
      with AD.

PMID- 18631960
TI  - A roadmap for the prevention of dementia: the inaugural Leon Thal Symposium.

PMID- 18631961
TI  - Commentary on "a roadmap for the prevention of dementia: the inaugural Leon Thal
      Symposium." An impending prevention clinical trial for Alzheimer's disease:
      roadmaps and realities.

PMID- 18631962
TI  - Commentary on "a roadmap for the prevention of dementia: the inaugural Leon Thal
      Symposium." Prevention of dementia: a few heretical proposals.

PMID- 18631963
TI  - Commentary on "a roadmap for the prevention of dementia: the inaugural Leon Thal
      Symposium." Prevention of dementia: roadmap or maintenance manual?

PMID- 18631964
TI  - Commentary on "a roadmap for the prevention of dementia: the inaugural Leon Thal
      Symposium".

PMID- 18631966
TI  - The amyloid cascade hypothesis.
AB  - The amyloid deposits in the brains of patients with Alzheimer's disease have
      attracted attention and are now considered not only an essential requirement for
      pathological diagnosis but also an important clue to the pathogenesis of the
      disease. This article looks critically at the basis of the "amyloid cascade
      hypothesis" to conclude that there are many issues that need to be resolved since
      they are inconsistent with the hypothesis.

PMID- 18631965
TI  - Commentary on "the Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe):
      design and baseline characteristics".

PMID- 18631967
TI  - Apolipoprotein E4 domain interaction: synaptic and cognitive deficits in mice.
AB  - BACKGROUND: Apolipoprotein E4 (apoE4), the major genetic risk factor for
      Alzheimer's disease (AD) and other neurodegenerative diseases, has three
      structural and biophysical properties that distinguish it from the other isoforms
      domain interaction, reduced stability, and lack of cysteine. Assessing their
      relative contributions to effects of apoE4-associated pathogenesis in AD is
      important from a mechanistic and therapeutic perspective, that is not possible
      using human apoE transgene or knock-in models. METHODS: We analyzed Arg-61 apoE
      mice, a gene-targeted model that selectively displays domain interaction.
      RESULTS: The mice displayed age-dependent loss of the synaptic protein
      synaptophysin in neocortex and hippocampus and had lower levels of the
      postsynaptic neuroligin-1. Activation of dentate gyrus granule neurons increased
      Arc expression 3.5-fold in wildtype mice but only 2.3-fold in Arg-61 mice. The
      losses of synaptic proteins caused a mild memory deficit in Arg-61 mice in the
      water-maze test. Since synaptic integrity requires efficient glutamate uptake, we
      measured astrocyte glutamate transporter 1 in the hippocampus. The level was
      reduced in Arg-61 mice, suggesting that inefficient glutamate uptake by
      astrocytes causes chronic excitotoxicity. Consistent with the reduced secretion
      of Arg-61 apoE by astrocytes in this model, cholesterol secretion was also
      reduced 34%. This reduction could also contribute to the synaptic deficits by
      limiting the availability of cholesterol for neuronal repair. CONCLUSIONS: Domain
      interaction in the absence of other structural characteristics of apoE4 is
      sufficient to cause synaptic pathology and functional synaptic deficits,
      potentially associated with astrocyte dysfunction and impaired maintenance of
      neurons. Therapeutic targeting of domain interaction might blunt effects of apoE4
      in neurodegenerative disease.

PMID- 18631968
TI  - Preference-based quality of life in patients with Alzheimer's disease.
AB  - BACKGROUND: This study was developed to evaluate the feasibility, reliability,
      and validity of use of patients' ratings of health preference measures as
      outcomes for cost-effectiveness analyses in persons with very mild to moderate
      Alzheimer's disease (AD). METHODS: Patients and caregivers completed ratings of
      the EuroQol-5D system (EQ-5D) and the Health Utilities Index Mark 2 (HUI2) and
      instruments that assess cognition, mood, insight, AD-specific and generic health
      related quality of life (QOL) and activities of daily living. RESULTS: Patients'
      HUI2 scores were reliable. EQ-5D scores were somewhat less so. Patients rated
      their utility high, with overall EQ-5D and HUI2 scores greater than 0.8. Neither
      the EQ-5D nor the HUI2 scores had a relationship with severity of cognitive
      impairment. Both the EQ-5D and the HUI2 had expected relationships with patient
      rated measures of QOL, function, mood, and specific subscales we hypothesized
      should be associated with patient preferences. Patient insight into functional
      and cognitive impairments had little association with their health preference
      scores. CONCLUSIONS: AD patients' scores on the EQ-5D and the HUI2 have many of
      the characteristics of valid preference measures. However, the proportions of
      persons who do not perceive any disability, the lack of association with the
      caregivers' ratings of activities of daily living, limited associations with
      insight, and no association with their Mini-Mental State Exam scores suggest that
      patients' reports of disability might reflect legitimate self-perceptions of mood
      and function that are associated with comorbidities rather than with AD.

PMID- 18631969
TI  - Caregivers' assessments of preference-based quality of life in Alzheimer's
      disease.
AB  - BACKGROUND: This study was designed to evaluate the feasibility, reliability, and
      validity of use of caregivers' ratings of two health preference measures as
      outcomes for cost-effectiveness analyses in persons with very mild to moderate
      Alzheimer's disease (AD). METHODS: Caregivers completed ratings of preference for
      AD patients' health by use of the EuroQol-5D system (EQ-5D) and the Health
      Utilities Index Mark 2 (HUI2). They also rated patients' cognition, mood, burden,
      AD-specific and generic health-related quality of life (QOL), and activities of
      daily living. RESULTS: Caregivers' HUI2 scores were reliable. Neither the
      caregiver ratings of the patients' health by use of the EQ-5D nor the HUI2 had a
      relationship with severity of cognitive impairment. Both the EQ-5D and the HUI2
      had expected relationships with caregivers' assessments of patients' function, AD
      specific QOL, and physical and mental health and selected subscales of the
      measures of AD-specific QOL and overall health. In addition, caregiver scores
      showed relationships with patient self-rated function, mood, and physical health
      but not AD-specific QOL. Caregiver burden was associated with caregivers' scores.
      CONCLUSIONS: Caregiver-completed ratings of preference for patients' health made
      by use of the EQ-5D and the HUI2 have many of the characteristics of valid
      preference measures. However, the lack of association with patient Mini-Mental
      Status Exam scores and patient self-rated AD-specific QOL and the associations
      with caregiver subjective burden might present limitations to their use as proxy
      measures for cost-effectiveness analyses.

PMID- 18631970
TI  - Decision analytic models for Alzheimer's disease: state of the art and future
      directions.
AB  - Decision analytic policy models for Alzheimer's disease (AD) enable researchers
      and policy makers to investigate questions about the costs and benefits of a wide
      range of existing and potential screening, testing, and treatment strategies.
      Such models permit analysts to compare existing alternatives, explore
      hypothetical scenarios, and test the strength of underlying assumptions in an
      explicit, quantitative, and systematic way. Decision analytic models can best be
      viewed as complementing clinical trials both by filling knowledge gaps not
      readily addressed by empirical research and by extrapolating beyond the surrogate
      markers recorded in a trial. We identified and critiqued 13 distinct AD decision
      analytic policy models published since 1997. Although existing models provide
      useful insights, they also have a variety of limitations. (1) They generally
      characterize disease progression in terms of cognitive function and do not
      account for other distinguishing features, such as behavioral symptoms,
      functional performance, and the emotional well-being of AD patients and
      caregivers. (2) Many describe disease progression in terms of a limited number of
      discrete states, thus constraining the level of detail that can be used to
      characterize both changes in patient status and the relationships between disease
      progression and other factors, such as residential status, that influence
      outcomes of interest. (3) They have focused almost exclusively on evaluating drug
      treatments, thus neglecting other disease management strategies and combinations
      of pharmacologic and nonpharmacologic interventions. Future AD models should
      facilitate more realistic and compelling evaluations of various interventions to
      address the disease. An improved model will allow decision makers to better
      characterize the disease, to better assess the costs and benefits of a wide range
      of potential interventions, and to better evaluate the incremental costs and
      benefits of specific interventions used in conjunction with other disease
      management strategies.

PMID- 18631971
TI  - Better cognitive performance in elderly taking antioxidant vitamins E and C
      supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache
      County Study.
AB  - Studies have shown less cognitive decline and lower risk of Alzheimer's disease
      in elderly individuals consuming either antioxidant vitamins or nonsteroidal anti
      inflammatory drugs (NSAIDs). The potential of added benefit from their combined
      use has not been studied. We therefore analyzed data from 3,376 elderly
      participants of the Cache County Study who were given the Modified Mini-Mental
      State examination up to three times during a period of 8 years. Those who used a
      combination of vitamins E and C supplements and NSAIDs at baseline declined by an
      average 0.96 fewer points every 3 years than nonusers (P < .05). This apparent
      effect was attributable entirely to participants with the APOE epsilon4 allele,
      whose users declined by 2.25 fewer points than nonusers every 3 years (P < .05).
      These results suggest that among elderly individuals with an APOE epsilon4
      allele, there is an association between using antioxidant supplements in
      combination with NSAIDs and less cognitive decline over time.

PMID- 18631972
TI  - Perspective on race and ethnicity in Alzheimer's disease research.
AB  - There are adequate scientific, public health, and ethical justifications for
      studying Alzheimer's disease (AD) in persons of varying race and ethnicity, but
      to be meaningful variables, race and ethnicity must be examined in context. The
      complex interactions between race, ethnicity, lifestyle, and environmental
      factors, such as climate and diet, require that future studies of AD in specific
      racial or ethnic groups attend to measures of racial/ethnic homogeneity and the
      assessment of the environment and the elements that comprise the ethnicity of
      groups under study. Instead of arbitrarily selecting specific racial or ethnic
      groups in the hope of finding important differences, it may be in the long run
      less costly and more efficient to recruit families with highly positive (or
      negative) family histories, to search within these groups for possible racial or
      ethnic differences, and to investigate the possible racial or ethnic reasons for
      those differences.

PMID- 18631973
TI  - Commentary on "Perspective on race and ethnicity in Alzheimer's disease
      research".
AB  - There are persistent disparities in Alzheimer's disease by race and ethnicity
      that are not well understood. The emphasis given to seeking a genetic basis for
      racial differences might be a distraction from the more relevant issue of
      identifying preventable causes of Alzheimer's disease. The majority of
      Alzheimer's disease cases are diagnosed as the late onset type and are unlikely
      to be inherited. Late onset Alzheimer's disease cases, therefore, more likely
      represent variations in gene expression than gene frequency. Although conceptual
      and methodologic problems have limited our understanding of this relationship,
      race-based studies provide important opportunities to understand the
      environmental factors associated with gene expression. Improving our
      understanding of the factors associated with race and ethnicity might help to
      clarify the epidemiology and course of Alzheimer's disease.

PMID- 18631974
TI  - Inflammation and Alzheimer's disease: possible role of periodontal diseases.
AB  - The molecular and cellular mechanisms responsible for the etiology and
      pathogenesis of Alzheimer's disease (AD) have not been defined; however,
      inflammation within the brain is thought to play a pivotal role. Studies suggest
      that peripheral infection/inflammation might affect the inflammatory state of the
      central nervous system. Chronic periodontitis is a prevalent peripheral infection
      that is associated with gram-negative anaerobic bacteria and the elevation of
      serum inflammatory markers including C-reactive protein. Recently, chronic
      periodontitis has been associated with several systemic diseases including AD. In
      this article we review the pathogenesis of chronic periodontitis and the role of
      inflammation in AD. In addition, we propose several potential mechanisms through
      which chronic periodontitis can possibly contribute to the clinical onset and
      progression of AD. Because chronic periodontitis is a treatable infection, it
      might be a readily modifiable risk factor for AD.

PMID- 18631975
TI  - Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis.
AB  - The association between the apolipoprotein E epsilon4 allele and Alzheimer's
      disease (AD) is well-established. Functional neuroimaging research has supported
      a compensatory mechanism recruitment hypothesis whereby nondemented epsilon4
      participants use additional cognitive resources to buffer against episodic memory
      declines in older age, a mechanism that is presumably associated with encroaching
      disease. However, recent studies have implicated a beneficial effect associated
      with the epsilon4 allele early in the life span. These studies suggest a revised
      hypothesis whereby epsilon4 persons perform better on cognitive measures early in
      the life span and then show greater recruitment of brain regions during
      performance to compensate for declines in older age caused by preclinical AD.

PMID- 18631977
TI  - Abnormal connectivity in the posterior cingulate and hippocampus in early
      Alzheimer's disease and mild cognitive impairment.
AB  - BACKGROUND: Brain imaging studies of early Alzheimer's disease (AD) have shown
      decreased metabolism predominantly in the posterior cingulate cortex (PCC),
      medial temporal lobe, and inferior parietal lobe. This study investigated
      functional connectivity between these regions, as well as connectivity between
      these regions and the whole brain. METHODS: Functional magnetic resonance imaging
      (fMRI) and diffusion tensor imaging (DTI) studies were performed in subjects with
      early AD, mild cognitive impairment (MCI), and normal controls. RESULTS: The data
      indicate both decreased fiber connections and disrupted connectivity between the
      hippocampus and PCC in early AD. The MCI group showed reduced fiber numbers
      derived from PCC and hippocampus to the whole brain. CONCLUSIONS: The fMRI and
      DTI results confirmed decreased connectivity from both the PCC and hippocampus to
      the whole brain in MCI and AD and reduction in connectivity between these two
      regions, which plausibly represents an early imaging biomarker for AD.

PMID- 18631976
TI  - The pilot European Alzheimer's Disease Neuroimaging Initiative of the European
      Alzheimer's Disease Consortium.
AB  - BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative
      (ADNI) has established a platform to track the brain changes of Alzheimer's
      disease. A pilot study has been carried out in Europe to test the feasibility of
      the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven academic sites
      of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with
      mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by
      using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic
      resonance imaging (MRI) scans, cerebrospinal fluid, and blood samples were
      shipped to central repositories. Medial temporal atrophy (MTA) and white matter
      hyperintensities (WMH) were assessed by a single rater by using visual rating
      scales. RESULTS: Recruitment rate was 3.5 subjects per month per site. The
      cognitive, behavioral, and neuropsychological features of the European subjects
      were very similar to their U.S. counterparts. Three-dimensional T1-weighted MRI
      sequences were successfully performed on all subjects, and cerebrospinal fluid
      samples were obtained from 77%, 68%, and 83% of AD patients, MCI patients, and
      controls, respectively. Mean MTA score showed a significant increase from
      controls (left, right: 0.4, 0.3) to MCI patients (0.9, 0.8) to AD patients (2.3,
      2.0), whereas mean WMH score did not differ among the three diagnostic groups
      (between 0.7 and 0.9). The distribution of both MRI markers was comparable to
      matched US-ADNI subjects. CONCLUSIONS: Academic EADC centers can adopt the ADNI
      platform to enroll MCI and AD patients and older controls with global cognitive
      and structural imaging features remarkably similar to those of the US-ADNI.

PMID- 18631979
TI  - Comparison of costs of care between patients with Alzheimer's disease and
      dementia with Lewy bodies.
AB  - BACKGROUND: The objective of this study was to compare total costs of care and
      its major components for community-living patients with Alzheimer's disease (AD)
      or dementia with Lewy bodies (DLB). This cross-sectional analysis of baseline
      data from the Predictors II Study took place in three university-based AD centers
      in the U.S. METHODS: Community-living patients clinically diagnosed with probable
      AD (n = 170) or DLB (n = 25) with a modified Mini-Mental State examination (mMMS)
      score > or =30, equivalent to a score of approximately > or =16 on the Folstein
      Mini-Mental State Examination (MMSE), participated in this study. Patient and
      informant reported on patients' use of direct medical care, direct nonmedical
      care, and informal care. Patients' clinical and demographic characteristics
      included global cognitive status (measured by MMSE), functional capacity
      (measured by Blessed Dementia Rating Scale), psychotic symptoms, behavioral
      problems, depressive symptoms, extrapyramidal signs, comorbidities, age, and sex.
      Costs were compared by using covariate matching methods. RESULTS: Unadjusted
      total costs and direct medical costs were not significantly different between AD
      and DLB patients. Compared with AD patients, unadjusted indirect costs were
      significantly higher and unadjusted direct nonmedical costs were significantly
      lower among DLB patients. After adjusting for age, sex, cognitive and functional
      status, differences in all cost components between DLB and AD patients were no
      longer statistically significant. CONCLUSIONS: Apparent cost differences were
      largely attributed to differences in patients' cognitive and functional status.
      However, the small sample size for DLB patients might have limited power to
      detect statistically significant differences in costs of care between these
      groups.

PMID- 18631978
TI  - Basal forebrain atrophy is a presymptomatic marker for Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common degenerative neurologic
      disorder. The onset of symptoms is insidious and follows a long period of
      progression of an asymptomatic pathology that proceeds in a precise anatomic and
      temporal sequence. Recent studies with quantitative magnetic resonance imaging
      techniques have shown the localization of the in vivo pathology of AD and its
      antecedent, mild cognitive impairment. The objective of the present study was to
      determine whether a sensitive and reliable marker for the presymptomatic phase of
      the disorder could be identified by longitudinal analysis of an initially
      asymptomatic, community-based population. METHODS: One hundred forty-eight
      healthy, cognitively normal participants in the Cardiovascular Health Study
      Cognition Study had detailed clinical examinations and magnetic resonance imaging
      scans in 1998-1999 and 2002-2003. Modulated voxel-based morphometry was used to
      compare regional brain volumes in subjects who remained cognitively normal after
      5 to 6 years of follow-up (n = 127) with those who developed probable AD during
      the same period (n = 21). RESULTS: Among normal subjects destined to develop AD,
      there was significant atrophy in the basal forebrain area as long as 4.5 years
      before the development of clinical symptoms. When the left hippocampus was also
      atrophic, the onset of dementia typically occurred earlier than in cases in which
      the atrophy was confined to basal forebrain. CONCLUSIONS: Atrophy in the basal
      forebrain precedes the development of AD in subjects with cognition judged to be
      normal by neuropsychological testing. The time required to develop dementia
      appears to be shortened if hippocampal atrophy is also present. These data
      indicate that atrophy restricted to medial basal forebrain is a biomarker that
      predicts development of probable AD in asymptomatic elderly subjects.

PMID- 18631980
TI  - Effect of parental family history of Alzheimer's disease on serial position
      profiles.
AB  - BACKGROUND: An exaggerated recency effect (ie, disproportionate recall of last
      presented items) has been consistently observed in the word list learning of
      patients with Alzheimer's disease (AD). Our study sought to determine whether
      there were similar alterations in serial position learning among asymptomatic
      persons at risk for AD as a result of parental family history. METHODS: Subjects
      included 623 asymptomatic middle-aged children of patients with AD (median, 53
      years) and 157 control participants whose parents survived to at least age 70
      without AD or other memory disorders. All participants were administered the Rey
      Auditory Verbal Learning Test, which requires learning and recall of 15 unrelated
      nouns. RESULTS: There was no significant difference in total words recalled
      between the AD children and control groups. However, compared with controls, AD
      children exhibited a significantly greater tendency to recall words from the end
      (recency) versus beginning (primacy) of the list. Serial position effects were
      unrelated to apolipoprotein allele epsilon 4 or depressive symptoms. CONCLUSIONS:
      Asymptomatic persons at risk for AD by virtue of family history do not show a
      difference in total words recalled compared with controls, but they exhibit a
      distinctly different serial position curve, suggesting greater reliance on
      immediate as opposed to episodic memory. This is the same serial position pattern
      observed in mild AD, seen here in reduced severity. Longitudinal follow-up is
      planned to determine whether changes in serial position patterns are a meaningful
      marker for preclinical detection of AD.

PMID- 18631981
TI  - Challenges to the recognition and assessment of Alzheimer's disease in American
      Indians of the southwestern United States.
AB  - Little is known about Alzheimer's disease (AD) and related neurodegenerative
      diseases in American Indian (AI) populations. To provide appropriate health care
      to elder AIs, whose population is expected to increase dramatically during the
      next 50 years, it is imperative to attain a better understanding of the
      interaction of culture and disease in this underserved population. Raising
      awareness in the AI population regarding the nature of dementia as it compares to
      normal aging and the development of culturally appropriate instruments to detect
      and stage AD are essential for future health care efforts. Barriers restricting
      clinical service to this population include historical factors relating to access
      to health care, cultural beliefs regarding aging, demographic diversity of the
      population, competing epidemiologic risk factors, and lack of proper assessment
      tools for clinicians.

PMID- 18631982
TI  - The "tipping point" in the Alzheimer's dialogue: it's all about the messenger.

PMID- 18631983
TI  - Diagnosis and assessment of Alzheimer's disease in diverse populations.

PMID- 18631984
TI  - The Italian version of Consortium to Establish a Registry of Alzheimer's Disease
      (CERAD).

PMID- 18631985
TI  - Leon Joel Thal, MD, 1944-2007: honoring his scientific legacy.

PMID- 18631986
TI  - Disease-modifying approaches to Alzheimer's disease: challenges and opportunities
      Lessons from donepezil therapy.
AB  - The era of disease modification as a therapeutic option for Alzheimer's disease
      (AD) is upon us. With dozens of novel drugs in development, there is more need
      than ever to develop biomarkers that distinguish normal aging from AD and AD from
      other dementias, track changes over time as disease progresses, and respond to
      interventions. Future trials will need to weight biomarker outcomes equal to
      cognitive outcomes especially when the biomarkers are linked to specific
      mechanisms, such as changes to beta amyloid (Abeta) deposition or brain volume.
      Since the advent of donepezil as a treatment for AD, new mechanisms of action of
      this molecule have been discovered. In this perspective, we review trial design
      and discuss the use of biomarkers by using lessons learned from previous trials
      conducted with cholinergic therapy.

PMID- 18631987
TI  - Current challenges for the successful treatment and prevention of Alzheimer's
      disease: treating the pathologies of the disease to change its clinical course.
AB  - The need to develop meaningful therapeutics for Alzheimer's disease is beginning
      to reach the general awareness of the public. Matching this awareness is the
      accelerated pace of compounds entering clinical trials. In addition, the
      development of diagnostic tools, biomarkers, and imaging modalities of the past
      decade in AD have improved dramatically. Unfortunately, the use of these
      diagnostic and scientific tools in clinical trial practice has not yet aligned or
      optimized. Most agents still target clinical end points associated with mild to
      moderate AD rather than focus on modulation of the underlying pathologies.
      Although there are obvious practical reasons for this, meaningful progress in
      other areas of medicine such as cardiology and oncology have generally targeted
      and monitored improvement or abatement of pathology as the primary end point as a
      successful disease-modifying strategy. Perhaps it is time to consider a similar
      approach in treatment of Alzheimer's disease.

PMID- 18631988
TI  - Prevention therapeutics of dementia.
AB  - In the absence of effective drugs for Alzheimer's disease (AD) and a validated
      roadmap or guideline for drug development, it is important to consider some of
      the limitations currently hampering AD drug development and some general
      principles for moving forward. This paper will address current barriers to
      developing drugs for AD, and offer new considerations for accelerating drug
      discovery, development, and clinical trials.

PMID- 18631989
TI  - More than a decade of estrogen neuroprotection.
AB  - Considerable evidence has emerged through more than a decade of research
      supporting the neuroprotective and cognition-preserving effects of estrogens.
      Such basic research coupled with various epidemiological studies led quickly to
      the assessment of Premarin for the treatment of mild to moderate Alzheimer's
      disease (AD), initiated by the Alzheimer's Disease Cooperative Study Group and
      headed by Dr. Leon Thal. While this and subsequent trials with Premarin (Wyeth
      Research, Monmouth Junction, New Jersey) and PremPro (Wyeth Research), a
      conjugated equine estrogen preparation plus medoxyprogresterone acetate, have not
      supported the use of estrogens in treating advanced AD, considerable inferences
      have been made from these placebo controlled trials of estrogens. Here, we aimed
      to put these AD trials of estrogens in perspective by considering the potential
      mechanisms of these potent neuroprotective estrogens, the role of estrogens in
      other neurodegenerative conditions, such as cerebral ischemia, and based on our
      current understanding of estrogen neurobiology, offer insight into the design of
      future clinical trails of estrogens for neuronal protection.

PMID- 18631990
TI  - Electroencephalography and event-related potentials as biomarkers of mild
      cognitive impairment and mild Alzheimer's disease.
AB  - BACKGROUND: Successful early detection of mild cognitive impairment (MCI) and
      Alzheimer's disease demands the identification of biomarkers capable of
      distinguishing individuals with prodromal or early cognitive impairment from
      healthy aging adults. Many laboratories are engaged in the discovery and
      validation of a wide array of potential genetic, proteomic, cognitive, and other
      types of biomarkers. METHODS: This review focuses on the application of
      quantitative electroencephalography (qEEG) and event-related potential (ERP)
      technologies as markers of prodromal impairment and early disease progression. It
      is the aim of this review to critically assess where this field currently stands,
      as well as future directions for EEG biomarker development. RESULTS: As a
      neuroimaging tool that is relatively inexpensive, potentially portable, and
      capable of providing high-density spatial mapping, qEEG offers a noninvasive,
      rapid, and replicable method for assessing age-related and disease-related
      neurophysiologic change. CONCLUSIONS: As different signature changes associated
      with particular stages of disease burden are identified and validated, we
      anticipate expanded application of qEEG as a reliable and sensitive biomarker(s)
      of MCI and early Alzheimer's disease.

PMID- 18631991
TI  - Memory health clinics-a first step to prevention.
AB  - A few years ago at the European Alzheimer's Disease Consortium-Alzheimer's
      Disease Cooperative Study meeting in Geneva we discussed with Leon Thal the
      possibility of building large multi-domain primary preventive international
      trials for Alzheimer's disease (AD) both in North America and in the European
      Union. AD is a multifactorial phenomenon, and we will be more likely to succeed
      in preventive trials if we build a strategy using all potential protective
      factors to have the most potential effect instead of a simple and unique
      intervention. Leon Thal suggested that this could have a much bigger impact than
      all the drugs we might ever hope to develop. The main objective of this article
      is to present the rationale for multi-domain preventive approaches.

PMID- 18631992
TI  - Optimizing phase II of drug development for disease-modifying compounds.
AB  - Phase II proof of concept (POC) (IIa) and dose-finding (IIb) studies represent
      major challenges in drug development. Prolonged development times delay effective
      therapies from reaching patients in need and adversely affect industry goals of
      decreasing time to market. Biomarkers including magnetic resonance imaging,
      cerebrospinal fluid tau and amyloid beta, and amyloid positron emission
      tomography have been considered as alternative outcomes to clinical measures.
      None of these is yet validated. Population enrichment is another possible
      solution to POC studies. More rapid progression to prespecified milestones can be
      achieved by enriching the population with risk factors. Conclusions based on
      enriched populations must be extrapolated with caution. Clinical measures with
      greater sensitivity than standard trial instruments might represent another
      strategy applicable to POC studies. Adaptive dose-response designs are being
      considered as a means of shortening phase IIb studies and creating a seamless
      interface with phase III. None of these strategies have been validated in a
      successful drug development program; all have some promise for reforming phase II
      and answering the central question of "how much information is sufficient to
      proceed to phase III without excessive risk for failure?"

PMID- 18631993
TI  - Leon Thal's vision for the treatment and prevention of Alzheimer's disease.

PMID- 18631995
TI  - We should not distinguish between symptomatic and disease-modifying treatments in
      Alzheimer's disease drug development.
AB  - The terms symptomatic and disease-modifying have become standard in discussions
      of Alzheimer's disease therapeutics, yet there is little justification for their
      use. Currently marketed drugs are presumed to be symptomatic because they lead to
      some degree of mean improvement over baseline and because of the widespread
      belief that their mechanisms are limited and their effects are completely
      reversible. Current trial methodologies cannot distinguish between symptomatic
      and disease-modifying effects. Furthermore, it is highly likely that many trials
      will demonstrate a combination of such effects at the level of the trial or at
      the level of the individual. The forces that drive this distinction are largely
      social, as opposed to scientific. It would be preferable for drugs to first seek
      an antidementia claim, preferably on the background of conventional therapies
      when possible, in trials that are as small and as short in duration as possible.
      Further refinements would come by demonstration of how substantial and how
      enduring the antidementia benefits are.

PMID- 18631996
TI  - Drug discovery and the prevention of Alzheimer's disease.
AB  - Progress in understanding the pathogenesis of Alzheimer's disease (AD) has
      advanced rapidly and has achieved parity in knowledge with other chronic
      degenerative diseases of the elderly. This knowledge has not yet been
      successfully translated into new and effective disease-modifying drugs. Many new
      clinical candidates are currently in clinical trials, and it is likely that some
      will be successful in achieving regulatory approval. Nevertheless, primary
      prevention of AD remains the ultimate and most important goal of research efforts
      because the unique clinical features of this dementing disease create a number of
      challenges for drug development, regulatory approval, and payment. Ultimately,
      the development of truly effective disease-modifying drugs through accelerated
      drug discovery is the only real pathway to primary prevention.

PMID- 18631994
TI  - Oral administration of circulating precursors for membrane phosphatides can
      promote the synthesis of new brain synapses.
AB  - Although cognitive performance in humans and experimental animals can be improved
      by administering omega-3 fatty acid docosahexaenoic acid (DHA), the neurochemical
      mechanisms underlying this effect remain uncertain. In general, nutrients or
      drugs that modify brain function or behavior do so by affecting synaptic
      transmission, usually by changing the quantities of particular neurotransmitters
      present within synaptic clefts or by acting directly on neurotransmitter
      receptors or signal-transduction molecules. We find that DHA also affects
      synaptic transmission in mammalian brain. Brain cells of gerbils or rats
      receiving this fatty acid manifest increased levels of phosphatides and of
      specific presynaptic or postsynaptic proteins. They also exhibit increased
      numbers of dendritic spines on postsynaptic neurons. These actions are markedly
      enhanced in animals that have also received the other two circulating precursors
      for phosphatidylcholine, uridine (which gives rise to brain uridine diphosphate
      and cytidine triphosphate) and choline (which gives rise to phosphocholine). The
      actions of DHA aere reproduced by eicosapentaenoic acid, another omega-3
      compound, but not by omega-6 fatty acid arachidonic acid. Administration of
      circulating phosphatide precursors can also increase neurotransmitter release
      (acetylcholine, dopamine) and affect animal behavior. Conceivably, this treatment
      might have use in patients with the synaptic loss that characterizes Alzheimer's
      disease or other neurodegenerative diseases or occurs after stroke or brain
      injury.

PMID- 18631997
TI  - Realizing the potential of positron emission tomography with 18F
      fluorodeoxyglucose to improve the treatment of Alzheimer's disease.
AB  - Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG-PET) thus far
      rarely has been used to advance the development of new treatments for Alzheimer's
      disease (AD). Now that FDG-PET with standard acquisition protocols for dementia
      is widely available, change in cerebral glucose metabolism is a feasible outcome
      variable for clinical drug trials. Individual analysis of FDG-PET results also
      might prove valuable. FDG-PET can detect metabolic changes very early in the
      course of AD and identify subjects for earlier treatment. FDG-PET reliably
      distinguishes AD from frontotemporal dementia so that only those most likely to
      benefit are enrolled in trials. Finally, objectively identifying phenotypic
      variations of AD with FDG-PET might have pathogenic and prognostic implications
      that can be used for personalized treatment approaches. The judicious use of FDG
      PET is needed to accelerate the evaluation of promising new drugs and more
      rationally target treatments for dementing diseases.

PMID- 18631998
TI  - Eyes on the prize: federal Alzheimer's research effort aims to facilitate
      interventions.
AB  - The public Alzheimer's disease (AD) research enterprise began in earnest in the
      mid-1970s with the creation by Congress of the National Institute on Aging at the
      National Institutes of Health. Today, AD research is a maturing field of study,
      with federal effort seeking to encourage the creativity and insights of
      individual investigators, and targeting special areas for emphasis. It is
      inspired by the legacy of our friend and colleague Leon Thal, whose innovative
      and collaborative approach to scientific research serves as a guidepost as we
      move toward the discovery of new and effective ways to prevent AD or slow its
      progression. This article describes the progress to date and potentially
      promising areas of study from the vantage point of the National Institute on
      Aging.

PMID- 18631999
TI  - Leon Thal and the therapeutic age of Alzheimer's disease.

PMID- 18632000
TI  - Current and future management of Alzheimer's disease.
AB  - The full span of Alzheimer's disease, from asymptomatic, pre-dementia, mild-to
      moderate stages, should be considered in the management. There are multiple
      research opportunities for better understanding and treatment of this condition.
      Ongoing cohort studies developed under Leon Thal's leadership will facilitate
      this process.

PMID- 18632001
TI  - A quarter century of advancing treatment for Alzheimer's disease with Leon J.
      Thal.

PMID- 18632002
TI  - The oldest old and the 90+ Study.
AB  - Memories are the gifts from friends and family that stay with us forever, unless
      a person develops Alzheimer's disease. Leon J. Thal left many, many memories,
      along with his desire to create a world where people did not lose them to the
      ravages of dementing illnesses. Working from the bench to the clinic, he was an
      incomparable leader, scientist, and educator to whom many, including myself, owe
      much. The present description of a clinical, genetic, and pathologic study of the
      oldest old contains much of Leon's influence. With data from >950 subjects, a
      brain repository, and our collection of DNA, the investigators of the 90+ Study
      are receptive to collaborations. Through our collective efforts, we will continue
      the scientific work that Leon so strongly supported.

PMID- 18632003
TI  - Home-based technologies: a new paradigm for conducting dementia prevention
      trials.
AB  - The approach toward treatment of Alzheimer's disease has evolved out of a large
      body of research, resulting in a common trial paradigm directed toward
      establishing efficacy and safety of putative treatments for dementia. To achieve
      the ultimate goal of preventing dementia, the future will build on this model but
      will need to incorporate new paradigms to more efficiently detect meaningful
      change over time. Among new innovations needed is the capability for assessing
      trajectories of change over many years. Intrinsic to this success is the ability
      to capture increasing variability as well as subject heterogeneity inherent in
      longitudinal aging cohorts. New methods of ubiquitous embedded home sensing and
      computing afford the opportunity to assess volunteers not only during long
      periods of time but with greater frequency and convenience. Clinical studies
      identifying the optimal ways of using these methods are needed.

PMID- 18632004
TI  - Differentiating Alzheimer's disease from dementia with Lewy bodies and
      Parkinson's disease with (+)-[11C]dihydrotetrabenazine positron emission
      tomography.
AB  - BACKGROUND: Several progressive neurologic disorders begin with cognitive decline
      or parkinsonism, notably Alzheimer's disease (AD), Parkinson's disease (PD), and
      dementia with Lewy bodies (DLB). We used positron emission tomography (PET) in
      attempts to differentiate these disorders. METHODS: We performed PET with (+)
      [11C]dihydrotetrabenazine ([11C]DTBZ) to examine blood-to-brain ligand transport
      (K(1)) and striatal monoaminergic presynaptic binding (distribution volume [DV])
      in 25 DLB, 30 PD, and 25 AD patients and 57 elderly controls (NC). RESULTS:
      [11C]DTBZ DV was decreased significantly in caudate nucleus, anterior putamen,
      and posterior putamen in DLB and PD compared with AD and NC. DLB and PD groups
      showed an anterior-to-posterior gradient of binding loss relative to NC, least in
      caudate nucleus and largest in posterior putamen. The gradient was significantly
      steeper in PD than DLB. Both PD and DLB showed significantly greater
      interhemispheric striatal binding asymmetry than NC, and PD had greater asymmetry
      than DLB. Cerebral cortical [11C]DTBZ K(1) was decreased diffusely by 4% to 8% in
      PD. Larger K(1) deficits occurred in AD and DLB temporoparietal and prefrontal
      association cortices and posterior cingulate cortex. Greater reduction of K(1)
      occurred in occipital cortex in DLB than AD. Receiver operating characteristic
      curve analyses distinguished DLB from AD more effectively on the basis of
      striatal DV than occipital K(1) and distinguished DLB from PD more effectively on
      the basis of cerebral cortical K(1) than striatal DV patterns. Overall, 90% of
      cases were properly classified by combining these measures. CONCLUSIONS: PET with
      [11C]DTBZ can differentiate DLB from both PD and AD in a single neuroimaging
      study.

PMID- 18632005
TI  - Chronic disease long-term drug prevention trials: lessons from the Alzheimer's
      Disease Anti-inflammatory Prevention Trial (ADAPT).
AB  - A randomized trial is a randomized trial. The basic ingredients do not change
      with different purposes whether for treatment or prevention of disease. Likewise,
      the problems and difficulties are mostly the same. But there are differences in
      approach and philosophy. Here we discuss problems in trials focused on healthy
      people to determine whether drugs can delay or prevent adverse health events,
      with the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) as an
      example. An important difference separating treatment trials from prevention
      trials is the length of time needed to demonstrate a difference with treatment.
      Related to this is the risk-benefit calculus of the trial. Treatment trials are
      aimed at "curing" or ameliorating disease, for example, as with trials involving
      people with Alzheimer's disease (AD) dementia to determine whether treatment is
      useful in dealing with the AD-induced dementia. Like other treatment trials,
      those targeting AD dementia balance these benefits against the risks of
      treatment. But by contrast, benefit in prevention trials, if any, will be found
      only in the absence or delay in disease onset, often after years of continuous
      treatment. As in ADAPT, the separation in timing of risk versus benefit often
      brings difficult decisions about how long to continue the trial in the absence of
      any apparent benefit to treatment. Other difficulties similarly relate to the
      length of prevention trials. In hopes that some lessons learned from ADAPT will
      assist future prevention trials, especially in the elderly, we describe several
      conundrums and problems experienced in this trial and attempt when possible to
      extend our observations to the larger class of long-term drug prevention trials.

PMID- 18632006
TI  - Dementia: is it time for a change in focus?
AB  - One of Dr Leon Thal's major contributions to Alzheimer's disease (AD) research
      was the network of clinical trials and his strong commitment to finding effective
      therapies for both the prevention and treatment of AD in the population. AD and
      dementia research has matured since the inception of the Alzheimer's Disease
      Center program from a primary social service problem to clinical-pathologic
      correlates and better definition of disease to evaluation of measures of
      cognition, in vivo images of the brain, and then to measures of beta amyloid and
      tau in vivo and relationship to clinical dementia. Unfortunately, we still do not
      know the etiology of AD or the relationship to other brain abnormalities such as
      vascular disease and Lewy bodies. We also do not have good preventive or
      treatment strategies. Both are badly needed. The critical question is whether
      this field is ready for a major change in focus from primarily a descriptive
      science to analytical, longitudinal studies testing new research hypotheses that
      will lead to better preventive and treatment approaches.

PMID- 18632007
TI  - A perspective on risks that impede development of drugs to modify the course of
      Alzheimer's disease: can they be reduced?
AB  - Discovery, development, and testing of new drugs with novel mechanisms and new
      indications are extremely risky. The number of new drugs introduced into clinical
      practice with new mechanisms and novel indications has not increased during
      recent years in spite of advances in biologic science. The sources of uncertainty
      leading to failure in drug development are discussed in three categories:
      biologic or target risk, clinical development uncertainty, and market
      uncertainty. Efforts to develop drugs that modify the course of Alzheimer's
      disease and/or delay the initial clinical manifestations of disease are subject
      to all three types of risk. Opportunities for government, academic researchers,
      advocacy groups, and the pharmaceutical industry to mitigate some of these risks
      and possibly speed the introduction of new therapies are mentioned.

PMID- 18632008
TI  - Challenges in clinical research on Alzheimer's disease: Leon Thal's legacy.

PMID- 18632009
TI  - Apolipoprotein E represents a potent gene-based therapeutic target for the
      treatment of sporadic Alzheimer's disease.

PMID- 18632010
TI  - The pre-mild cognitive impairment, subjective cognitive impairment stage of
      Alzheimer's disease.
AB  - BACKGROUND: Subjective cognitive impairment (SCI) has been a common, but poorly
      understood condition, frequently occurring in older persons. METHODS: The past
      and the emerging literature on SCI and synonymously named conditions is reviewed.
      RESULTS: Findings include: (1) There is support from at least one longitudinal
      study for a long-standing concept of SCI as a pre-mild cognitive impairment (MCI)
      condition lasting approximately 15years. (2) There are complex relationships
      between SCI and depression and anxiety. (3) Differences in SCI subjects from age
      matched non-SCI persons are being published in terms of cognitive tests,
      hippocampal gray matter density, hippocampal volumes, cerebral metabolism, and
      urinary cortisol levels. Psychometric and dementia test score differences between
      SCI and MCI subjects have long been evident. (4) Predictive electrophysiologic
      features of subsequent decline in SCI subjects are being published. CONCLUSIONS:
      Studies of therapeutic agents in SCI treatment and resultant Alzheimer's disease
      prevention appear to be feasible. These trials are also necessary from a public
      health perspective.

PMID- 18632011
TI  - Primary care diabetes: promoting research in primary care.

PMID- 18632012
TI  - Monitoring for improvement: quality indicators for diabetes care.

PMID- 18632013
TI  - Is prevention of Type-2 diabetes feasible and efficient in primary care? A
      systematic PubMed review.
AB  - AIM: To answer: (1) Do we have effective treatments to improve prognosis for
      those identified at risk of Type-2 diabetes? (2) Will prevention be cost
      effective? METHODS: A systematic search was done in PubMed using the following
      search strategy: "diabetes AND prevention AND (IFG OR IGT)". Restrictions were:
      "English, Meta-Analysis, Randomized Controlled Trial, Review, Humans". RESULTS:
      Few randomised controlled preventive trials were found. Almost all were done in
      research settings in people with high risk of developing Type-2 diabetes. It
      seems possible to either delay or prevent Type-2 diabetes through lifestyle
      interventions and medication. Cost-utility analyses are few in number and come to
      very different conclusions as to whether health policy should promote prevention
      of Type-2 diabetes. CONCLUSION: Intervention studies using lifestyle counselling
      and drug therapy in research settings illustrate promising results with lowering
      of the incidence of Type-2 diabetes, meaning that Type-2 diabetes can be delayed
      or prevented. It is, however, questionable whether these interventions are cost
      effective. We need studies in routine clinical settings evaluating morbidity,
      mortality and cost-effectiveness as primary outcomes. While waiting for these
      studies to prove cost-effective, patients with pre-diabetes should be treated
      according to their 10-year risk of cardiovascular disease following present
      guidelines.

PMID- 18632014
TI  - High prevalence of diabetes among immigrants from non-European countries in
      Sweden.
AB  - Patients with diabetes aged 35-64 years from four primary health care centres in
      Stockholm County were identified from electronic patient records (EPRs): diabetes
      prevalence occurred 414 of 15,317 men, and 250 of 15,388 women. The age- and sex
      standardized prevalence of diabetes was as follows: Non-European immigrants,
      5.82% (95% CI 5.06-6.58), European immigrants 1.96% (95% CI 1.53-2.39), and
      Swedish-born subjects 1.80% (95% CI 1.63-1.97). In conclusion, non-European
      immigrants showed a three-fold higher prevalence of diabetes compared to Swedish
      born subjects.

PMID- 18632015
TI  - Quality indicators for type-2 diabetes care in practice guidelines: an example
      from six European countries.
AB  - INTRODUCTION: Diabetes mellitus patients need a multidisciplinary management and
      rigorous follow up. Quality indicators are important to assess and improve the
      quality of the health-care delivery. Less straightforward, however, is choosing
      which indicators to use for the assessment of the disease management. METHODS:
      Review of guidelines. Process and outcome indicators were extracted out of type-2
      diabetes guidelines from Belgium and its neighbouring countries. The "most
      evidence based" indicators were derived after applying a "best evidence" ratio.
      RESULTS: Thirty-four indicators were classified in five diabetes management
      topics: (1) control of glycaemia, (2) early detection of glycaemic complications,
      (3) treatment of glycaemic complications, (4) cardiovascular disease and, (5)
      quality of life. Target values to outcome indicators and appropriate
      specifications to process indicators were not assigned because direct transfer to
      different countries is not possible without considering contextual information
      such as typical preconditions of every society and health-care system.
      CONCLUSION: Although not all aspects of care are described in guidelines, five
      'mini' lists of highly valuable indicators for optimal treatment in the field of
      type-2 diabetes could be drawn up. The target sets for indicators' values and
      specifications are a matter of ongoing concern because evidence changes over
      time.

PMID- 18632016
TI  - Obstacles to adherence in living with type-2 diabetes: an international
      qualitative study using meta-ethnography (EUROBSTACLE).
AB  - Quantitative studies failed to determine variables which consistently explain
      adherence or non-adherence to treatment recommendations. Qualitative studies
      identified issues such as the quality of the health provider-health receiver
      relationship and the patient's health beliefs. According to these findings, 39
      focus groups of 246 people living with type-2 diabetes were conducted in seven
      European countries, assessing health beliefs, communication with caregivers and
      problems encountered in adhering to treatment regimens. Meta-ethnography was
      later applied to make a qualitative meta-analysis. Obstacles to adherence are
      common across countries, and seem to be related less to issues of the health-care
      system and more to patient's knowledge about diabetes, beliefs and attitudes and
      the relationship with health-care professionals. The resulting key themes are
      course of diabetes, information, person and context, body awareness and
      relationship with the health care provider. Meta-ethnography is a feasible tool
      for the meta-analysis of multilingual qualitative data and leads to a richer
      account.

PMID- 18632017
TI  - Attitudes of GPs to the diagnosis and management of impaired glucose tolerance:
      the practitioners' attitudes to hyperglycaemia (PAtH) questionnaire.
AB  - AIMS: To develop and pilot a survey instrument assessing general practitioners'
      (GP) attitudes to the diagnosis and management of one form of pre-diabetes,
      impaired glucose tolerance (IGT) and to assess the performance of the
      questionnaire. METHODS: Qualitative data together with an audit were used to
      generate questionnaire items, which were then subjected to a process of pre
      piloting and piloting to generate a finalised item list. The pilot questionnaire
      was sent to 222 principal GPs in three PCTs in South West England. The first
      fifty responders were asked to complete the questionnaire again 2 weeks later.
      Principal components analysis with a Varimax rotation was used to detect latent
      factors within the data that may help to explain the attitudes of GPs. RESULTS:
      The response rate after one reminder was 54.1%. Four robust factors were
      identified which were internally consistent (range of Cronbach's alpha=0.79
      0.65), homogeneous (item-total correlations=0.60-0.21), and stable (test-retest
      correlation=0.74-0.58) accounting for 31.1% of the variance. The predictive
      validity of the item list was assessed (P=0.02 for factor 1). CONCLUSIONS: The
      PAtH questionnaire identifies four factors that help to describe GPs attitudes to
      the diagnosis and management of IGT.

PMID- 18632019
TI  - New global recommendations: a multidisciplinary approach to improving outcomes in
      diabetes.
AB  - Up to two-thirds of people with type-2 diabetes do not achieve glycaemic targets,
      increasing their risk of serious complications. New global recommendations from
      The Global Partnership for Effective Diabetes Management offer practical, simple
      advice for the diabetes management team to help individuals reach glycaemic
      goals. The recommendations focus on four areas: achieving optimal glycaemic
      control, targeting the underlying pathophysiology of the disease, treating
      earlier and intensively with combination therapy, and adopting a holistic
      approach. This article reviews the new recommendations and suggests that they
      offer a route to achieving guideline-based targets and improving outcomes in the
      real-life healthcare setting.

PMID- 18632020
TI  - The nature of quality and the goals of diabetes care.

PMID- 18632021
TI  - Shared and delegated systems are not quick remedies for improving diabetes care:
      a systematic review.
AB  - BACKGROUND: Type 2 diabetes is an important, chronic condition notorious for its
      costly and disabling complications. Nowadays, enhanced cooperation is expected to
      improve the quality of diabetes care and reduce risks for chronically ill
      patients. It is, however, questionable whether this assumption is evidence based.
      METHODS: Using a structured literature search, we selected systematic reviews,
      randomised controlled trials (RCTs) and other effect evaluations regarding the
      sharing and allocation of diabetes care. RESULTS: We selected 22 studies to
      include in this review. The process of care improved in all studies investigating
      this quality aspect. HbA1c improved in seven reviews and in five other studies.
      All included reviews and four RCTs were unable to demonstrate a positive effect
      on blood pressure. Total cholesterol improved in two reviews and five other
      studies. CONCLUSIONS: The sharing and allocation of diabetes care leads to
      significant reduction in HbA1c and improves the process of care. However, this
      improvement has not as yet led to better cardiovascular risk management. For a
      number of reasons, a truly accurate estimation of the results of shared and
      allocated diabetes care within the Dutch diabetes care system is not possible.

PMID- 18632022
TI  - Screen detected subjects with type 2 diabetes and impaired glucose tolerance have
      more adverse cardiovascular risk than subjects with impaired fasting glucose
      especially when they are obese: the ADDITION Netherlands study.
AB  - AIMS: To determine cardiovascular risk of screen detected subjects with type 2
      diabetes (T2DM), impaired glucose tolerance (IGT) and impaired fasting glucose
      (IFG). To examine whether BMI is an effect modifier regarding the relation
      between level of glucose regulation and cardiovascular risk factors. METHODS:
      From 2002 to 2003, 29,251 persons, aged 50-70 years, participated in a population
      based diabetes screening programme. Diagnosis was based on the 1999 WHO criteria.
      Characteristics were assessed of 285 subjects with T2DM, 175 with IGT and 218
      with IFG. RESULTS: IFG did not resemble IGT and T2DM regarding weight and blood
      pressure. BMI (kg/m2) was 27.3+/-4.4, 29.5+/-5.7, 30.7+/-5.6 in IFG, IGT, DM,
      respectively; systolic blood pressure (mmHg) 150+/-25, 161+/-24, 162+/-23;
      diastolic blood pressure (mmHg) 84+/-12, 89+/-12, 90+/-11. The poorer the
      glycaemic control, the worse levels of BMI, blood pressure and lipids. When BMI
      was higher, cardiovascular risk factors were more adverse, especially in subjects
      with diabetes. CONCLUSIONS: Subjects with IFG had lower blood pressure and weight
      than subjects with IGT and T2DM suggesting IFG is a condition with less risk to
      develop cardiovascular diseases. Effect modification by BMI was found.

PMID- 18632023
TI  - Diagnosed diabetic retinopathy in France, Italy, Spain, and the United Kingdom.
AB  - AIM: The objective of this study was to describe the proportion and
      characteristics of patients diagnosed with diabetic retinopathy (DR) in France,
      Italy, Spain, and the United Kingdom (UK). METHODS: To estimate the proportion of
      patients with type 1 and type 2 diabetes diagnosed with DR, we conducted a cross
      sectional survey of general practitioners in each country using physician
      records. In addition, diabetes specialists were recruited in Italy and Spain. We
      extracted data from the medical notes of a sample of DR patients to characterize
      DR severity and clinical characteristics. RESULTS: The average number of
      physicians per country was 41 (range: 34-49). The proportion of diagnosed DR
      ranged from 10.3% (95% CI, 6.7-14.0%) in Spain to 19.6% (95% CI, 16.0-23.1%) in
      the UK. Of 752 DR patients studied, 53.9% were male; mean age (+/-SD) was 64.2+/
      12.8 years. Consistently across countries, mild non-proliferative DR was the most
      common severity level of diagnosed DR. Proliferative DR (PDR) ranged from 19.7%
      (France) to 31.5% (UK). Diabetic macular oedema was reported in approximately 10%
      of patients. Hypertension (73.1%), dyslipidemia (63.2%), and neuropathy (52.1%)
      were the most common co-morbidities. CONCLUSIONS: Country-specific prevalence of
      diagnosed DR may reflect clinical management of diabetes, healthcare systems, or
      record-keeping accuracy. Across countries, up to 30% of DR patients had a
      diagnosis of PDR, which could suggest that patients are diagnosed only when their
      disease is advanced.

PMID- 18632024
TI  - Poor control and management of cardiovascular risk factors among Albanian
      diabetic adult patients.
AB  - BACKGROUND: Cardiovascular and metabolic risk factors represent potential targets
      for intervention. A good metabolic control, associated with control of blood
      pressure and cholesterol levels is proven to reduce the risk of cardiovascular
      disease among individuals with diabetes mellitus. OBJECTIVES: To examine 2004
      2005 medical records of adults with previously diagnosed diabetes and to evaluate
      the fulfillment of diabetes guidelines treatment, for the metabolic control and
      management of cardiovascular risk factors. RESEARCH, DESIGN AND METHODS: We
      reviewed the data from the National Register of Diabetes (Tirana district),
      updated during this period. As guidelines we used the ADA 2006 Recommendations
      for metabolic control, HTA, lipid profile and aspirin therapy. RESULTS: We
      examined 7259 medical records. Only 14.58% of the patients had an HbA1c <7%.
      Central obesity was present in 39% of our patients. Overall, only 31.9% of our
      patients achieved the target for blood pressure (SBP<130 mmHg and DBP<80 mmHg).
      Two-third of our patients had total cholesterol >200 mg/dl. In total, only 5.5%
      of our patients attained recommended goals of cardiovascular risk factors for
      HbA1c, blood pressure and lipid profile. CONCLUSIONS: The follow-up of diabetic
      patients during the transient period in Albania is marked by a deterioration of
      diabetes metabolic control and poor management of cardiovascular risk factors.
      Further public health efforts are needed for better control of these risk factors
      among adults with diagnosed diabetes.

PMID- 18632025
TI  - The relationship between patient education and glycaemic control in a South
      African township.
AB  - OBJECTIVE: To investigate if there is a relationship between patients' perceived
      diabetes education and their glycaemic control. METHODS: Two hundred and forty
      seven diabetic (both DM 1 and DM 2) patients who were treated for diabetes in a
      primary nurse led health care clinic in South Africa were analyzed. Patients were
      interviewed, and information was retrieved from the patients' medical record.
      RESULTS: Fasting blood glucose levels were <7.0 mmol/l in 17.6% of the patients,
      79.3% of the patients had a BMI>2788.2% of the patients received information
      about diabetes, the majority received information from the nurse. Patients with a
      higher educational level and patients who received education tended to have a
      better glycaemic control. (n.s.) Significantly more patients who received
      information had a good or acceptable FBG level (p=0.03). The recorded prevalence
      of chronic complications was low. CONCLUSIONS: Glycaemic control was suboptimal
      in the big majority of patients. Education had a positive effect on glycaemic
      control, albeit not impressive. Also in South Africa poor health literacy should
      be taken into account in diabetes education.

PMID- 18632026
TI  - Family doctors' assessment of patient- and health care system-related factors
      contributing to non-adherence to diabetes mellitus guidelines.
AB  - OBJECTIVE: The aim of this study was to assess family doctors' opinions on the
      patient- and health care system-related factors contributing to non-adherence to
      diabetes mellitus clinical practice guidelines (CPG) in Estonia. RESEARCH DESIGN
      AND METHODS: Descriptive postal survey using a self-administered questionnaire.
      RESULTS: Of the 354 doctors who received the questionnaire 46% (n=163) responded.
      Seventy-six percent of them have type 2 diabetes guidelines. Low awareness of
      diabetes and its complications as well as patients' low motivation to change
      their lifestyle were considered to be the biggest difficulties in managing
      individual patients. In addition to the most often listed problems non-compliance
      with medical regimen, patients' financial problems and their nonattendance were
      mentioned. The greatest health care system-related barriers to practices
      providing desirable care were the lack of special diabetes education for nurses
      and underfunding, and an inadequate number of patients' educational materials.
      The patient-related issues were regarded as problems in 96% of the cases and
      health care system-related factors were mentioned in 79% of the cases.
      CONCLUSIONS: Family doctors in Estonia consider patient-related factors to be key
      issues in non-adherence to diabetes mellitus clinical practice guidelines.

PMID- 18632027
TI  - HIV and diabetes.

PMID- 18632028
TI  - Gut hormones, incretin mimetics and gliptins: new understanding and novel
      therapies in type 2 diabetes.

PMID- 18632029
TI  - The quality dilemma.
AB  - In the language and logic of the free market, providers of health care will have
      to demonstrate the quality of their work. However, in this setting quality is
      only interpreted in quantitative ways and consequently does not necessarily do
      justice to good physicians. Moreover, both outcome measures and process measures
      have serious drawbacks. An emphasis on outcome measures will disadvantage
      physicians working in deprived areas and doctors managing more complicated cases.
      Although process measures give the most direct information on the physician's
      performance, their evidence base is not always as straightforward as commonly
      supposed. Finally, measurement of quality indicators is complicated and time
      consuming. Physicians should be aware of the drawbacks of quality measurement and
      of the poor effects of quality improvement strategies on patient outcomes.

PMID- 18632030
TI  - Payment by results--a model for other diabetes healthcare systems?

PMID- 18632031
TI  - Prevention of diabetes: a reality in primary care?

PMID- 18632032
TI  - Rapid increase in the incidence of clinically diagnosed type 2 diabetes in
      Chinese in Harbin between 1999 and 2005.
AB  - AIM: To examine the recent trend in the incidence of clinically diagnosed type 2
      diabetes during the period of 1999-2005 in Harbin, China. METHODS: The records of
      newly diagnosed type 2 diabetes from hospitals and clinics in Harbin were
      reported to the Harbin Centre for Disease Control and Prevention. About 3 million
      (33%) of the total population were from six metropolitan districts and over 6
      million (67%) from the surrounding counties. Incidence rates and incidence rate
      ratios (IRR) were estimated using Poisson regression. RESULTS: During the
      observational period, 26,953 new cases of diagnosed type 2 diabetes were
      reported. Among them, 16,367 were from the metropolitan region and 10,586 from
      the surrounding counties. The incidence rate of type 2 diabetes in the
      metropolitan region was 3.19 (95% CI: 3.11, 3.27) times as high as that in the
      surrounding counties. Females had higher incidence rates in younger age groups
      (<54 years) and lower rates in older age groups (55+ years) than their male
      counterparts. The incidence increased over time during the period of 1999-2005 by
      an average of 12% per year (IRR=1.12, 95% CI: 1.11, 1.13). Similar increasing
      rates were observed in both the county and metropolitan regions. CONCLUSIONS: The
      incidence of diagnosed type 2 diabetes has increased dramatically in recent
      years. Although an increasing trend in the incidence of type 2 diabetes exists in
      both metropolitan and county regions, the county region currently has a
      substantially lower incidence rate than the metropolitan region.

PMID- 18632033
TI  - Diagnosis of diabetic peripheral neuropathy among patients with type 1 and type 2
      diabetes in France, Italy, Spain, and the United Kingdom.
AB  - AIMS: The objective of this study was to describe the proportion and
      characteristics of patients with type 1 and type 2 diabetes diagnosed with
      diabetic peripheral neuropathy (DPN) in France, Italy, Spain, and the United
      Kingdom (UK). METHODS: A cross-sectional survey was administered to general
      practitioners and diabetes specialists. Existing physicians' records were used to
      quantify the frequency of DPN diagnoses, and notes from patients' medical charts
      were used to characterize symptoms. RESULTS: The average number of physicians per
      country was 41 (range of 34-49). The proportion of diabetes patients diagnosed
      with DPN ranged from 9.6% (95% CI, 7.1-12.2) in Spain to 23.1% (95% CI, 15.4
      30.7) in Italy. Of 913 DPN study patients, 55.0% were male, and 78.5% had type 2
      diabetes. Mean age was 64.5+/-12.5 years. A DPN diagnosis was based primarily on
      symptoms. Approximately 27% of patients had no documented neurological
      examination. "Prickling" was the most common DPN symptom recorded in France,
      Italy, and Spain, and "numbness" was the most common in the UK. CONCLUSIONS:
      Country-specific estimates of DPN diagnosis may reflect clinical management of
      diabetes and DPN. A substantial number of diagnoses were not associated with a
      record of a neurological examination.

PMID- 18632034
TI  - Acceptability and effects of an educational leaflet on infections in type 2
      diabetes patients: a randomized controlled trial in primary care.
AB  - AIM: To determine the acceptability of an educational leaflet regarding the
      prevention and treatment of infections of the lower respiratory tract (LRTIs) and
      urinary tract (UTIs) and to determine the effects of the leaflet on knowledge and
      attitude of DM2 patients in primary care. METHOD: In a randomized controlled
      intervention trial 200 DM2 patients enlisted in two practices, one urban and one
      rural, from the Utrecht general practitioners Research Network (HNU) were
      selected. Per practice, 50 patients were randomly assigned to the intervention
      group and 50 to the control group. The intervention was a leaflet on diabetes and
      LRTIs and UTIs based on the results of focus group interviews. The leaflet was
      sent to the patients homes. The outcome measures were acceptability of the
      leaflet and differences in knowledge and attitude, measured by a questionnaire.
      RESULTS: The mean age was 68 years and 55% was male. There were no substantial
      differences in characteristics between the two groups. Among the intervention
      group, the leaflet was appreciated as understandable (100%) and inviting (79%).
      Compared to the control group, specific knowledge and attitude did not
      substantially differ. Patients in the intervention group had a slightly more
      positive attitude about 'being attentive to signs indicating pneumonia' (median
      difference, 1 point; p=.003) and they also answered 'UTI is mostly caused by a
      bacteria' more often correctly (risk difference, 18%; 95% CI, 4-33%, p=.016).
      CONCLUSION: A leaflet on prevention and treatment of LRTIs and UTIs is considered
      acceptable among DM2 patients, but a multi-faceted educational approach may be
      needed to improve health behavioral determinants.

PMID- 18632035
TI  - International survey of insulin pump users: Impact of continuous subcutaneous
      insulin infusion therapy on glucose control and quality of life.
AB  - AIMS: To record the characteristics and attitude of patients treated with
      continuous subcutaneous insulin infusion (CSII), and the impact on glycaemic
      control in a large number of CSII patients in routine daily life. METHODS: A
      structured questionnaire was distributed to 36,450 CSII patients from Europe and
      North America to determine patient characteristics, therapy characteristics,
      medical results, complications and treatment satisfaction. RESULTS: A 38%
      response rate was achieved, 92% from patients with Type 1 diabetes. The responses
      indicated that CSII users achieved good glycaemic control with a mean HbA(1c)
      level of 7.0+/-1.1%. A significant correlation was observed between HbA(1c) and
      the number of blood glucose measurements per day. Four to five blood glucose
      measurements are needed in a majority of patients to reach optimal glucose
      control in intensely treated diabetic patients. The clinical benefits of CSII
      therapy were matched by patient experience and improvements in quality of life.
      There were 5.74 episodes per patient year of hypoglycaemia needing assistance,
      although the number of serious adverse effects recorded was dependent on
      patient's self-reporting. CONCLUSIONS: These data suggest patients using CSII
      therapy achieve good metabolic control, are highly satisfied, and experience an
      acceptably small number of complications.

PMID- 18632036
TI  - Facility-level variations in patient-reported footcare knowledge sufficiency:
      implications for diabetes performance measurement.
AB  - AIMS: To evaluate medical center variation in self-reported knowledge of footcare
      practices by veterans at high risk for lower extremity complications. METHODS: We
      utilized a previously validated footcare-specific survey from 772 (44% response
      rate) veterans with diabetes and high-risk foot conditions at eight Veterans
      Administration facilities that contained items on knowledge of basic (such as how
      to inspect feet) and specialized self-foot care practices (such as cutting nails
      and shaving calluses). Linear regression models were used to evaluate facility
      level variation in unadjusted and adjusted education (controlling for age,
      schooling, general, and foot health). RESULTS: Participants' average age was 67
      years, 94% were male and 34% had 13 years of education. The mean facility basic
      knowledge score on a four-point ordinal scale was 3.1 (range: 2.9-3.3), where
      1=no knowledge and 4=enough knowledge. The specialized knowledge score, using the
      same scale, was 2.52 (range: 2.2-2.8). There were significant (p<0.005)
      differences among facilities in both unadjusted and adjusted basic and
      specialized footcare knowledge. CONCLUSIONS: Patient self-reported footcare
      knowledge was suboptimal and significantly varied across medical centers with and
      without adjustment for foot-risk factors, general health, and demographic
      factors.

PMID- 18632037
TI  - An insight into undiagnosed impaired glucose regulation.
AB  - Type 2 diabetes is responsible for considerable morbidity, mortality and cost to
      society. There is good evidence that lifestyle modification and pharmacological
      intervention are effective means of delaying, and possibly preventing, the onset
      of type 2 diabetes in individuals with impaired glucose regulation. The aim of
      this study was to estimate the number of patients treated at our district general
      hospital over a 28-day period who had impaired glucose regulation and so would be
      suitable candidates for intervention. The results reveal that 518 patients passed
      through our hospital during this period with evidence of impaired glucose
      regulation, but only 95 of these patients were formally investigated for
      diabetes. Of those who were investigated further, over one fifth were shown to
      have impaired glucose regulation. We suggest that a random plasma glucose test
      may provide a useful means to identify a population for formal screening for
      diabetes.

PMID- 18632038
TI  - Diabetes prevalence and quality of diabetes care among Lebanese or Turkish
      immigrants compared to a native Danish population.
AB  - OBJECTIVES: To describe Type 2 diabetes prevalence and care among Turkish (T) and
      Lebanese (L) immigrants as compared to native Danes (DK) in the county of Aarhus.
      METHOD: Data from The National Health Service Registry, The Regional Laboratory
      Database and The Danish National Hospital Registry were collected from 2000
      through 2003 to identify and describe known diabetes in a background population
      of 244.426 citizens in the age group of 40-70 years living in the County of
      Aarhus. RESULTS: The age-standardised prevalence of Type 2 diabetes was 3.6%
      (DK), 18.9% (L) and 19.8% (T). In 2003, HbA1c was measured at least once in 84%
      (DK), 87% (L) and 83% (T) of the patients. In 2003, 72% (DK), 53% (L) and 51% (T)
      had an HbA1c <8% (p<0.05) and less than 50% of all groups had a total-cholesterol
      <5.0 mmol/l. In 39% (DK), 35% (L) and 37% (T) of the patients, no examination for
      retinopathy was registered during the period of 2000-2003. A cardiovascular
      diagnosis was registered in 27% (DK), 32% (L) and 33% (T) of the patients (p=NS).
      CONCLUSION: Compared to native Danes, Lebanese and Turkish immigrants had a much
      higher prevalence of Type 2 diabetes and worse glycaemic regulation. The routine
      monitoring of diabetes care for native Danes, Lebanese or Turkish immigrants were
      similar. Overall, diabetes care is not satisfactory neither for native Danes, nor
      Lebanese or Turkish immigrants.

PMID- 18632040
TI  - Problem of using hemoglobin A1C measurement in endemic area of hemoglobinopathy.
AB  - Diabetes mellitus (DM) is a frequent disorder affecting individuals of all ages.
      Glycohemoglobin (GHb) has a key role in the assessment of glycemic control in
      diabetic patients. Generally, GHb is measured as hemoglobin (Hb) A1C and is the
      result of an irreversible non-enzymatic glycation of the beta chain of hemoglobin
      A. HbA1C is used routinely to assess long term glycemic control in patients with
      DM. A variety of patient- and laboratory-related factors can adversely affect the
      measurement of HbA1C in patients harboring Hb variants or derivatives. In this
      article, problem of using hemoglobin A1C measurement in endemic area of
      hemoglobinopathy is addressed.

PMID- 18632039
TI  - The EUCCLID study: proposed European study on care and complications in people
      with type 2 diabetes in primary care.
AB  - AIM: The EUCCLID study aims to compare the quality of type 2 diabetes (DM2) care
      and the prevalence of complications in primary care DM2 patients in Europe.
      DESIGN: A cross-sectional survey consisting of three parallel studies: (1) study
      on actual clinical practice; (2) study on patient's perspective of diabetes care;
      (3) study on general practitioner's perspective of diabetes care. METHODS:
      Patients will be randomly selected from a list of all patients known to the
      participating GPs with DM2 for whom the GP is the main diabetes care provider.
      Exclusion criteria will include people with type 1 diabetes mellitus, diabetes of
      pregnancy, serious mental illness, unable to complete a questionnaire in national
      language or unable to give written informed consent. Approximately 12,000
      patients will be included. Participants will have a detailed medical history and
      anthropometric measurements, blood and urine will be collected and questionnaires
      will be taken. Endpoints will include quality indicators of clinical DM2 care,
      prevalence of diabetic complications, knowledge, attitudes, barriers and
      behaviour affecting good control in DM2 patients, quality of life and patients'
      satisfaction with diabetes care. We will also determine primary care physician's
      attitudes, behaviour and perception of barriers to deliver effective diabetes
      care.

PMID- 18632041
TI  - Primary care diabetes in Hungary.
AB  - People with diabetes are cared for by family physicians and special ambulances.
      Diagnostic and therapeutic interventions are similar to other European countries.
      The Hungarian Diabetes Association is the lead contributor to scientific events
      and professional and patient education. Close cooperation between health
      suppliers and patient's education is central to further development. Ongoing
      health reform may modify the access to care.

PMID- 18632042
TI  - Payment by results.

PMID- 18632043
TI  - Rosiglitazone and the thiazolidinediones: a changing context.

PMID- 18632044
TI  - Cognitive dysfunction and diabetes: implications for primary care.
AB  - It is increasingly recognized that diabetes mellitus can lead to long-term
      complications in the brain. Clinically, these complications are manifested in
      alterations in cognitive functioning. This paper offers an overview on the impact
      of diabetes on cognition and provides leads for the evaluation and management of
      cognitive disturbances in patients with diabetes in a primary care setting. The
      main message is that while some patient groups appear to be at increased risk of
      cognitive impairments, in the majority of patients diabetes is not associated
      with the development cognitive decrements that would be regarded as clinically
      relevant. Frank impairments of cognition mainly occur in patients above the age
      of 65, often in association with vascular co-morbidity. Other groups at risk for
      cognitive decrements are children with an early age at diabetes onset and
      patients with clinically manifest retinopathy or other microvascular
      complications. No specific treatment options are available, but for now treatment
      of vascular risk factors and attention for glycaemic control appears to be a
      logical approach. Given the recent progress in this field, new treatments to
      prevent cognitive impairment in patients with diabetes may hopefully become
      available in the near future.

PMID- 18632045
TI  - Knowledge of blood pressure targets among patients with diabetes.
AB  - INTRODUCTION: Tight blood pressure (BP) control is the single most important
      intervention to prevent cardiovascular mortality among patients with diabetes
      mellitus (DM). However, little is known about how many patients have specific
      target BP levels or the factors associated with patients' knowledge of these
      targets. OBJECTIVES: (1) To determine what proportion of patients with diabetes
      have BP targets; (2) To determine patient characteristics associated with having
      a BP target. METHODS: Cross-sectional, anonymous survey of 500 randomly selected
      outpatients with hypertension and DM receiving care in any Veterans Health
      Administration outpatient clinic in 2003. We examined multivariate associations
      between patient characteristics and having targets for BP. Covariates included
      age, race, gender, and education level; and factors specific to diabetes and BP
      treatment, including medication use, diabetes duration, and number of visits to
      diabetes healthcare providers in the previous year. RESULTS: Three hundred and
      seventy-eight (80%) patients responded. Although most (91%) had blood glucose
      targets, fewer than 60% reported having a BP target. In multivariate analyses,
      college education was associated with having a BP target (AOR 1.97 [95% CI: 1.16
      3.34]). CONCLUSIONS: Less than two-thirds of diabetic, hypertensive patients had
      BP targets. Encouraging patients to set target BPs may promote hypertension self
      management in this high-risk patient population. Less educated patients may
      especially benefit from interventions to increase awareness of BP targets.

PMID- 18632046
TI  - Screening for type 2 diabetes in primary care using a stepwise protocol: the
      Diabscreen study.
AB  - AIM: To evaluate a stepwise protocol in opportunistic screening for type 2
      diabetes. METHODS: From 2000 to 2001, in 11 Dutch general practices (n=49,229) we
      invited at-risk patients during usual care for a capillary fasting plasma glucose
      (cFPG1) measurement. If >6.0 mmol/l, a second sample (cFPG2) was taken on another
      day, followed by a venous sample (vFPG) if cFPG2>6.0 mmol/l and cFPG1 or 2> or
      =7.0 mmol/l. RESULTS: Of 3724 at-risk patients invited for a cFPG1, 3335 (90%)
      returned for the measurement. Ultimately, in 125 (4%) of them a vFPG was
      measured. In 101 out of 125 patients the vFPG was > or =7.0 mmol/l, giving a
      positive predictive value of our protocol of 81%. CONCLUSION: A stepwise
      screening protocol including two subsequent capillary blood glucose measurements
      from a portable blood glucose meter is well applicable in screening for type 2
      diabetes in primary care.

PMID- 18632047
TI  - Primary care diabetes in Ukraine.
AB  - People with diabetes in Ukraine are cared for by endocrinology specialists.
      Implementation of the National Diabetes Plan solved the problem of free insulin
      supply. However, many problems of diabetic care, including increase of
      accessibility to some laboratory tests and treatments, are still unresolved. An
      increase of life expectancy among diabetic patients has been noted during the
      past 5 years.

PMID- 18632048
TI  - Primary care diabetes in the Republic of Ireland.
AB  - The Republic of Ireland has a mixed public and private healthcare system.
      Individuals with diabetes have traditionally been managed in specialist settings,
      particularly in urban centres. This is changing rapidly with more and more type 2
      diabetes being managed in primary care. As yet there is no structured national
      diabetes care programme though there is currently an Expert Advisory Group on
      Diabetes meeting to make recommendations to government regarding setting up such
      a service which will integrate diabetes care between primary and specialty
      sectors.

PMID- 18632050
TI  - Quick remedies for improving diabetes care: a contradiction in terms.

PMID- 18632049
TI  - New treatments for type 2 diabetes--the DPP4 inhibitors.
AB  - Sitagliptin (brand name Januvia) the first of a new class of oral agents, the
      DPP4 inhibitors, which lower blood glucose in type 2 diabetes has recently been
      launched in UK. Another DPP4 inhibitor vildagliptin is due to be launched soon,
      and there are several others in the pipeline. This article gives an overview of
      this new class of medications.

PMID- 18632085
TI  - Aging preserves the ability to perceive 3D object shape from static but not
      deforming boundary contours.
AB  - A single experiment investigated how younger (aged 18-32 years) and older (aged
      62-82 years) observers perceive 3D object shape from deforming and static
      boundary contours. On any given trial, observers were shown two smoothly-curved
      objects, similar to water-smoothed granite rocks, and were required to judge
      whether they possessed the "same" or "different" shape. The objects presented
      during the "different" trials produced differently-shaped boundary contours. The
      objects presented during the "same" trials also produced different boundary
      contours, because one of the objects was always rotated in depth relative to the
      other by 5, 25, or 45 degrees. Each observer participated in 12 experimental
      conditions formed by the combination of 2 motion types (deforming vs. static
      boundary contours), 2 surface types (objects depicted as silhouettes or with
      texture and Lambertian shading), and 3 angular offsets (5, 25, and 45 degrees).
      When there was no motion (static silhouettes or stationary objects presented with
      shading and texture), the older observers performed as well as the younger
      observers. In the moving object conditions with shading and texture, the older
      observers' performance was facilitated by the motion, but the amount of this
      facilitation was reduced relative to that exhibited by the younger observers. In
      contrast, the older observers obtained no benefit in performance at all from the
      deforming (i.e., moving) silhouettes. The reduced ability of older observers to
      perceive 3D shape from motion is probably due to a low-level deterioration in the
      ability to detect and discriminate motion itself.

PMID- 18632086
TI  - Non-linear gaining in precision aiming: making Fitts' task a bit easier.
AB  - The role of information in the processes underlying kinematic trajectory
      formation was examined by manipulating the relation between effector space
      (movement of a hand-held stylus on a graphics tablet) and task space (movement of
      a cursor on a screen where targets were presented) in a precision aiming task
      with five different levels of task difficulty. Movement patterns were found to
      evolve as a function of the flow of information in task space, with participants
      (N=13) producing more rapid and more fluent movements when the mapping between
      spaces included the softening-spring characteristics typical of behavioural
      patterns at higher levels of task difficulty. We conclude that the kinematic
      changes (movement time and pattern) observed when task difficulty increases
      result from informational influences. Information affects behavioural dynamics at
      the level of the parameters without affecting the underlying dynamical structure.

PMID- 18632087
TI  - Investigation of the transmission of fore and aft vibration through the human
      body.
AB  - Understanding the behavior of human body under the influence of vibration is of
      great importance for the optimal motor vehicle system design. Therefore, great
      efforts are being done in order to discover as many information about the
      influence of vibration on human body as possible. So far the references show that
      the major scientific attention has been paid to vertical vibration, although
      intensive research has been performed lately on the other sorts of excitation. In
      this paper, the results of the investigation of behavior of human body, in seated
      position, under the influence of random fore and aft vibration are shown. The
      investigation is performed by the use of an electro-hydraulic simulator, on a
      group of 30 healthy male occupants. Experiments are performed in order to give
      results to improve human body modeling in driving conditions. Excitation
      amplitudes (1.75 and 2.25 m/s(2) rms) and seat backrest conditions (with and
      without inclination) were varied. Data results are analyzed by partial coherence
      and transfer functions. Analyses have been performed and results are given in
      detail. The results obtained have shown that the human body under the influence
      of random excitations behaves as a non-linear system and its response depends on
      spatial position. Obtained results give necessary data to define structure and
      parameters of human biodynamic model with respect to different excitation and
      seat backrest position.

PMID- 18632088
TI  - An investigation of the use of health building notes by UK healthcare building
      designers.
AB  - Building design in the healthcare industry presents a complex architectural
      challenge. This paper reports a qualitative study to investigate the use of
      building design guidance by healthcare architects and planners in the United
      Kingdom. Sixteen architects, healthcare planners and facilities managers
      participated in 11 group and individual interviews. The data were analysed using
      NVivo2, resulting in three main themes: changes in the design culture over 20
      years for the context of guidance use; quality of the evidence base to support
      the guidance; and future guidance needs to include patient expectations, new
      building techniques and generic room templates. The use of guidance was variable,
      with some participants seeing a clear role for new (more standardised) guidance
      in the future, whereas others were more concerned about loss of design freedom.
      Two clear roles for ergonomics were identified to: (1) facilitate the
      participation of patients and clinicians in the design process; and (2) generate
      new research evidence with respect to spatial requirements for clinical
      activities to support standardisation. These recommendations pertain specifically
      to healthcare facility design for the National Health Service in the UK.

PMID- 18632089
TI  - Connectivity between posterior parietal cortex and ipsilateral motor cortex is
      altered in schizophrenia.
AB  - BACKGROUND: Recent advances have highlighted the hypothesis of schizophrenia as a
      disorder causing defective connectivity among distinct cortical regions.
      Neurophysiological evidence supporting this hypothesis, however, is still
      lacking. METHODS: In the present study, we used a novel twin-coil transcranial
      magnetic stimulation (tcTMS) approach to investigate ipsilateral parieto-motor
      connectivity in 20 schizophrenic patients (14 medicated, 6 unmedicated) and in 15
      healthy age-matched volunteers. RESULTS: In healthy subjects, a conditioning TMS
      pulse applied over the ipsilateral posterior parietal cortex (PPC) at 90% of
      resting motor threshold (RMT) intensity was able to increase the excitability of
      the hand area of the right primary motor cortex, with peaks at interstimulus
      intervals (ISIs) of 4 and 15 msec. This paradigm of stimulation failed to reveal
      any facilitatory parieto-motor interaction in medicated and unmedicated
      schizophrenic patients. The between-group difference in paired-pulse facilitation
      was not ISI-specific. In following analyses, we found that the effects across
      ISIs induced by PPC conditioning at 90% RMT correlated with the Global Assessment
      Functioning score and with the negative subscale of the Positive and Negative
      Syndrome Scale, showing that patients with a better global functioning and lower
      negative symptoms had less impaired connectivity. Moreover the same parameter
      correlated with illness duration. CONCLUSIONS: Parieto-motor connectivity is
      impaired in schizophrenia. Cortico-cortical disconnection might be a core feature
      of schizophrenia.

PMID- 18632091
TI  - Role of mesenteric lymph nodes and aging in secretory IgA production in mice.
AB  - Although it is known that Peyer's patches are the major inductive site for S-IgA
      production and B1 cells contribute to half of the IgA plasma cells detected in
      the gut lamina propria, the type of contribution of mesenteric lymph nodes to the
      process is still unclear. Cytokines such as TGF-beta, IL-10, IL-4, IL-5, and IL
      6, are required to promote IgA class switching and IgA synthesis. Aging-related
      alterations in T and B cells and in cytokine production are already known. Some
      reports have also proposed that S-IgA production might be altered in aged
      animals. Herein, we investigated the role of MLN and aging in S-IgA production.
      Two- to 18-month-old BALB/c mice were used to evaluate aging-related alterations
      and MLN were removed to study its role in S-IgA production. We found that MLN are
      important, although not essential for S-IgA production. In addition, we showed
      that production of IgA-related cytokines are well preserved in MLN but not in PP
      of aged mice and that S-IgA levels are not affected by aging. Our results suggest
      that MLN may play a complementary role in S-IgA production mostly in aged
      animals.

PMID- 18632092
TI  - The paranormal mind: how the study of anomalous experiences and beliefs may
      inform cognitive neuroscience.

PMID- 18632090
TI  - Genome-wide linkage analyses of quantitative and categorical autism
      subphenotypes.
AB  - BACKGROUND: The search for susceptibility genes in autism and autism spectrum
      disorders (ASD) has been hindered by the possible small effects of individual
      genes and by genetic (locus) heterogeneity. To overcome these obstacles, one
      method is to use autism-related subphenotypes instead of the categorical
      diagnosis of autism since they may be more directly related to the underlying
      susceptibility loci. Another strategy is to analyze subsets of families that meet
      certain clinical criteria to reduce genetic heterogeneity. METHODS: In this
      study, using 976 multiplex families from the Autism Genome Project consortium, we
      performed genome-wide linkage analyses on two quantitative subphenotypes, the
      total scores of the reciprocal social interaction domain and the restricted,
      repetitive, and stereotyped patterns of behavior domain from the Autism
      Diagnostic Interview-Revised. We also selected subsets of ASD families based on
      four binary subphenotypes, delayed onset of first words, delayed onset of first
      phrases, verbal status, and IQ > or = 70. RESULTS: When the ASD families with IQ
      > or = 70 were used, a logarithm of odds (LOD) score of 4.01 was obtained on
      chromosome 15q13.3-q14, which was previously linked to schizophrenia. We also
      obtained a LOD score of 3.40 on chromosome 11p15.4-p15.3 using the ASD families
      with delayed onset of first phrases. No significant evidence for linkage was
      obtained for the two quantitative traits. CONCLUSIONS: This study demonstrates
      that selection of informative subphenotypes to define a homogeneous set of ASD
      families could be very important in detecting the susceptibility loci in autism.

PMID- 18632093
TI  - Bridging neuroscience and education: a two-way path is possible.

PMID- 18632094
TI  - Deficient mental own-body imagery in a neurological patient with out-of-body
      experiences due to cannabis use.
AB  - In the present work, we report repeated out-of-body experiences (OBEs) in a
      patient with tetraplegia and severe somatosensory loss due to multiple sclerosis
      and predominant involvement of the cervical spinal cord. OBEs were experienced on
      a daily basis and induced by cannabis treatment that was started for severe
      spasticity with painful cramps and cloni. In order to investigate the link
      between OBEs and mental own-body imagery, the patient was asked to imagine
      himself in the position and visual perspective that is generally reported during
      OBEs, using front- and back-facing schematic human stimuli. Performance was
      measured before and after cannabis consumption. First, our data reveal that the
      patient was less accurate for back-facing than front-facing stimuli. This was
      found before and after cannabis consumption and is the opposite pattern to what
      is generally observed in healthy participants and in our control subjects (who
      did not use cannabis). We refer to this as lesion effect and argue that this
      relative facilitation for stimuli reflecting the position and visual perspective
      that is generally reported during OBEs might be due to recurrent and spontaneous
      own-body transformations during the patient's frequent OBEs. Secondly, we found a
      cannabis effect, namely a performance improvement in the back-facing condition
      while performance in the front-facing condition remained unchanged, after
      cannabis administration. We argue that cannabis administration may interfere with
      own-body imagery when reflecting the actual body position and only when
      associated with brain damage. Based on these data we propose an extended
      neurological model for own-body illusions including multisensory and sensorimotor
      mechanisms, cannabis consumption, and cortical and subcortical processing.

PMID- 18632095
TI  - Category-specific recognition and naming deficits following resection of a right
      anterior temporal lobe tumor in a patient with atypical language lateralization.
AB  - We present a patient with right-hemispheric speech lateralization who exhibited
      severe recognition and naming deficits for unique objects (famous faces and
      landmarks) and grossly normal recognition and naming performances for nonunique
      objects (animals and man-made objects) following an anterior right temporal lobe
      (TL) resection of a ganglioglioma. While recognition deficits have been reported
      for famous faces following right temporal pole lesions, and for landmarks and
      geographic regions following right TL damage in general, this is the first
      reported case of both recognition and naming deficits for these objects resulting
      from a single lesion. These results are consistent with research suggesting that
      the neuroanatomic substrates for the recognition and naming of unique objects lie
      in the anterior TL regions. Left temporal pole lesions have been associated with
      naming deficits for unique objects while right temporal pole lesions have been
      associated with recognition deficits for unique objects. However, these findings
      suggest that the substrates of naming can be located in homotopic regions of the
      right hemisphere when language lateralization is atypical. As various object
      categories appear to have different neuroanatomical representations in the TLs,
      we discuss the possible benefits of sampling a wider array of objects during
      cortical stimulation mapping of language.

PMID- 18632096
TI  - A blood-CSF barrier function controls embryonic CSF protein composition and
      homeostasis during early CNS development.
AB  - In vertebrates, early brain development takes place at the expanded anterior end
      of the neural tube, which is filled with embryonic cerebrospinal fluid (E-CSF).
      Most of the proteins contained within the E-CSF, which play crucial roles in CNS
      development, are transferred from the blood serum. Two important questions are
      how E-CSF is manufactured and how its homeostasis is controlled. In this respect,
      the timing of the blood-CSF barrier formation is controversial. Recently, the
      concept of a functional dynamic barrier has been introduced. This type of barrier
      is different from that found in adults and is adapted to the specific
      requirements and environment of the developing nervous system. In this study, we
      injected a number of proteins into the outflow of the heart and into the cephalic
      cavities and examined their transport rate between these two embryo compartments.
      The results indicated that a functional blood-CSF barrier dynamically controls E
      CSF protein composition and homeostasis in chick embryos before the formation of
      functional choroid plexuses. We also showed that proteins are transferred through
      transcellular routes in a specific area of the brain stem, close to the ventral
      mesencephalic and prosencephalic neuroectoderm, lateral to the ventral midline,
      in particular blood vessels. This study contributes to our understanding of the
      mechanisms involved in CNS development, as this blood-CSF interface regulates the
      composition of E-CSF by regulating its specific composition.

PMID- 18632097
TI  - Imaginal discs regulate developmental timing in Drosophila melanogaster.
AB  - The regulation of body size in animals involves mechanisms that terminate growth.
      In holometabolous insects growth ends at the onset of metamorphosis and is
      contingent on their reaching a critical size in the final larval instar. Despite
      the importance of critical size in regulating final body size, the developmental
      mechanisms regulating critical size are poorly understood. Here we demonstrate
      that the developing adult organs, called imaginal discs, are a regulator of
      critical size in larval Drosophila. We show that damage to, or slow growth of,
      the imaginal discs is sufficient to retard metamorphosis both by increasing
      critical size and extending the period between attainment of critical size and
      metamorphosis. Nevertheless, larvae with damaged and slow growing discs
      metamorphose at the same size as wild-type larvae. In contrast, complete removal
      of all imaginal tissue has no effect on critical size. These data indicate that
      both attainment of critical size and the timely onset of metamorphosis are
      regulated by the imaginal discs in Drosophila, and suggest that the termination
      of growth is coordinated among growing tissues to ensure that all organs attain a
      characteristic final size.

PMID- 18632098
TI  - Fishing, fish consumption, and awareness about warnings in a university community
      in central New Jersey in 2007, and comparisons with 2004.
AB  - Fish are a healthy source of protein, but the risks from consuming fish have
      become a national concern. Over the past 7 years, there have been a number of
      national advisories regarding saltwater fish. Fish consumption patterns and
      public knowledge about advisories and warnings have been examined for at-risk
      populations, but there is little information about the latter for a general
      population, or of temporal trends in such information acquisition. Information
      about the benefits and health risks of consuming fish, health warnings from the
      New Jersey Department of Environmental Protection and the Food and Drug
      Administration, belief in these warnings, and trust in different sources of
      information were examined in a sample of 460 people within a university community
      in central New Jersey in 2007. The null hypothesis of no differences in fishing,
      consumption, and knowledge about advisories as a function of age, gender,
      ethnicity, and education was tested. In 2007, only 30% of the study population
      fished, and 83% of the study population ate fish, either commercial or self
      caught. There were differences in fishing behavior, consumption patterns, and
      awareness of advisories as a function of gender, ethnicity, age, and education.
      Most notably, nearly twice as many men as women fished, Whites fished more and
      Blacks and Indian/Pakistanis fished less than other ethnic groups, and people
      aged 23-35 fished more than did others. About 8% of fish meals were from self
      caught fish, 32% were eaten in restaurants, and 60% were of fish bought in stores
      and cooked at home. Men ate more meals of self-caught fish than did females, and
      Asians ate more meals of fish in restaurants, and Blacks ate more meals of store
      bought fish than other ethnic groups. The total number of fish meals consumed per
      month increased significantly with age. Overall, more people had heard about the
      benefits (92%) than the risks (78%) of fish consumption. When asked whom they
      trust for information about health benefits and risks from eating fish, doctors
      were rated the highest, followed by professors; friends and fishermen were rated
      the lowest. We then examined whether there were any changes from 2004 to 2007 in
      the knowledge of the health benefits and warnings about fish consumption, and the
      trustworthiness of different sources of information. In other words, have
      communication efforts of the state and federal agencies resulted in any
      appreciable increase in overall awareness of the benefits or risks of fish
      consumption. The greatest change in the parameters examined from 2004 to 2007 was
      an overall decrease in fish consumption from an average of 7.9 meals per month in
      2004 to about six meals per month in 2007. This suggests that the unintended
      effect of some of the warnings and advisories is to decrease overall fish
      consumption, rather than to switch from fish species with high levels of
      contaminants to those with low levels.

PMID- 18632100
TI  - Behavioral plasticity in rainbow trout (Oncorhynchus mykiss) with divergent
      coping styles: when doves become hawks.
AB  - Consistent and heritable individual differences in reaction to challenges, often
      referred to as stress coping styles, have been extensively documented in
      vertebrates. In fish, selection for divergent post-stress plasma cortisol levels
      in rainbow trout (Oncorhynchus mykiss) has yielded a low (LR) and a high
      responsive (HR) strain. A suite of behavioural traits is associated with this
      physiological difference, with LR (proactive) fish feeding more rapidly after
      transfer to a new environment and being socially dominant over HR (reactive)
      fish. Following transport from the UK to Norway, a switch in behavioural profile
      occurred in trout from the 3rd generation; HR fish regained feeding sooner than
      LR fish in a novel environment and became dominant in size-matched HR-LR pairs.
      One year after transport, HR fish still fed sooner, but no difference in social
      dominance was found. Among offspring of transported fish, no differences in
      feeding were observed, but as in pre-transported 3rd generation fish, HR fish
      lost fights for social dominance against size-matched LR opponents. Transported
      fish and their offspring retained their distinctive physiological profile
      throughout the study; HR fish showed consistently higher post-stress cortisol
      levels at all sampling points. Altered risk-taking and social dominance
      immediately after transport may be explained by the fact that HR fish lost more
      body mass during transport than did LR fish. These data demonstrate that some
      behavioural components of stress coping styles can be modified by experience,
      whereas behavioural plasticity is limited by genetic effects determining social
      position early in life story.

PMID- 18632101
TI  - Trauma experience in the UK and Ireland: analysis of orthopaedic training using
      the FHI eLogbook.
AB  - Surgical trainees routinely provide evidence of their training and operative
      experience for assessment. National comparative data on the number of procedures
      performed during training was previously unavailable in the UK. Since 2003 every
      trainee in Trauma and Orthopaedics (T&O) in the UK and Ireland has submitted data
      recording their operative experience electronically via the Faculty of Health
      Informatics (FHI) eLogbook. This provides detailed data on trainee, trainer,
      hospital and training programme performance. This data has been analysed for
      trauma surgery. By March 2007 there were 1053 T&O Specialist Registrars with
      operations logged. Trauma operations performed and uploaded during the previous 3
      years have been included. Each trainee's work is analysed by 'year-in-training'
      (YIT, 1-6). Data on levels of supervision and potentially missed opportunities
      (where the trainee was present but assisted rather than performed the operation)
      was analysed. The mean number of trauma operations performed annually by trainees
      was 109, 120, 110, 122, 98 and 84 (total 643) for YIT 1-6, respectively. 22% of
      the operations at which a trainee was present were potentially missed
      opportunities. A high level of experience is gained in hip fracture surgery (121
      operations performed), intramedullary nailing (38) and ankle (47) stabilisation
      over the 6 years of training. However, the mean number of tendon repairs (18),
      tension band wires (13), external fixators (12) and children's supracondylar
      fracture procedures (9) performed is low. We also report figures for complex
      fracture stabilisation. The eLogbook remains a powerful tool which can provide
      accurate information to support in-depth analysis of trainees, trainers, and
      training programmes. Based on this analysis, we suggest 'standard setting' to
      identify trainees performing fewer operations than required during their
      training. We have also established a baseline which can be used to identify the
      consequences of changes to length of training and working hours.

PMID- 18632102
TI  - Celiac serology in women with severe pre-eclampsia or delivery of a small for
      gestational age neonate.

PMID- 18632103
TI  - Duration of bladder catheterization after surgery for obstetric fistula.
AB  - OBJECTIVE: To compare the surgical outcome at discharge and at 6-months follow up
      in patients who underwent repair of obstetric fistulae with postoperative bladder
      catheterization for 10, 12, or 14 days. METHODS: A retrospective study of 212
      obstetric fistula patients who underwent repair with postoperative bladder
      catheterization for 10 days (group 1), 12 days (group 2), and 14 days (group 3)
      at the Bahir Dar Hamlin Fistula Center in Ethiopia. Fistulas were classified
      according to Goh's system. RESULTS: There were 68 women (32%) in group 1, 62
      women (29%) in group 2, and 82 women (39%) in group 3. There was a significant
      difference in the extent of urethral involvement, fistula size, and degree of
      vaginal scarring among the 3 groups, with the more extensively damaged patients
      catheterized for longer. Breakdown of repair was seen in 1.5% of patients in
      group 1, none in group 2, and 2% in group 3 (P=0.47). CONCLUSION: Postoperative
      catheterization for 10 days may be sufficient for management of less complicated
      obstetric vesicovaginal fistulae.

PMID- 18632104
TI  - Perineal tear involving perineal body and rectovaginal septum during spontaneous
      vaginal delivery.

PMID- 18632105
TI  - Pulse methotrexate versus pulse actinomycin D in the treatment of low-risk
      gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To compare the efficacy of methotrexate and actinomycin D as single
      agents in first-line chemotherapy for women with low-risk gestational
      trophoblastic neoplasia (LR-GTN). METHODS: A total of 131 women with LR-GTN were
      randomized to receive a weekly pulsed dose of 30 mg/m(2) of methotrexate
      intramuscularly (n=81) or a pulsed intravenous bolus of 1.25 mg/m(2) of
      actinomycin D every 2 weeks (n=50). An additional cycle was administered as
      consolidation treatment following normalization of the serum level of beta-human
      chorionic gonadotropin (<5 IU/L). RESULTS: Complete remission was achieved in
      48.14% of patients in the methotrexate group and 90.00% in the actinomycin D
      group (P<0.001). The mean number of treatment cycles needed to achieve response
      was lower in the actinomycin D group (4.8 vs 6.8). The risk of treatment failure
      was 26.4 greater with methotrexate than with actinomycin D (95% confidence
      interval, 5.7-22.6; P<0.001). CONCLUSION: Actinomycin D may be a better option
      than methotrexate as a first-line chemotherapy agent for patients with LR-GTN.

PMID- 18632106
TI  - Composite bounds on the elastic modulus of bone.
AB  - Advances in diagnosis and treatment of some bone disorders can be made by
      understanding the linkage between mineral content and mechanical function. Bone
      is approximately half by volume a hydrated protein network, and the remainder is
      a biomineral analogue of hydroxyapatite. In the current work, paired measurements
      of mechanical properties, using nanoindentation, and of bone mineral volume
      fraction, computed from quantitative back-scattered electron imaging, were made
      on six different types of normal and outlier bone samples. Local elastic modulus
      was plotted against mineral fraction and compared with predictions of engineering
      bounds for a two-phase composite material. Experimental data spanning the
      composite bounds showed no one-to-one relationship between mechanical stiffness
      and bone composition, excluding the possibility of any single, simple composites
      model for bone at nanometer length-scales.

PMID- 18632107
TI  - A multi-modular tensegrity model of an actin stress fiber.
AB  - Stress fibers are contractile bundles in the cytoskeleton that stabilize cell
      structure by exerting traction forces on the extracellular matrix. Individual
      stress fibers are molecular bundles composed of parallel actin and myosin
      filaments linked by various actin-binding proteins, which are organized end-on
      end in a sarcomere-like pattern within an elongated three-dimensional network.
      While measurements of single stress fibers in living cells show that they behave
      like tensed viscoelastic fibers, precisely how this mechanical behavior arises
      from this complex supramolecular arrangement of protein components remains
      unclear. Here we show that computationally modeling a stress fiber as a multi
      modular tensegrity network can predict several key behaviors of stress fibers
      measured in living cells, including viscoelastic retraction, fiber splaying after
      severing, non-uniform contraction, and elliptical strain of a puncture wound
      within the fiber. The tensegrity model can also explain how they simultaneously
      experience passive tension and generate active contraction forces; in contrast, a
      tensed cable net model predicts some, but not all, of these properties. Thus,
      tensegrity models may provide a useful link between molecular and cellular scale
      mechanical behaviors and represent a new handle on multi-scale modeling of living
      materials.

PMID- 18632108
TI  - Simultaneous trace determination of nine organic UV-absorbing compounds (UV
      filters) in environmental samples.
AB  - A new sensitive method has been successfully developed and validated for the
      simultaneous determination and quantification of nine estrogenic UV filters
      (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4, 4,4
      dihydroxybenzophenone, ethyl-4-aminobenzoate, 2-ethyl-hexyl-4
      trimethoxycinnamate, 3-(4-methylbenzylidene)-camphor, 3-benzylidene-camphor) in
      different environmental matrices. After optimisation of extraction conditions for
      the best recovery of polar to lipophilic compounds from fish tissue and a
      subsequent lipid clean-up in HPLC, fish extraction recoveries exceeded 72% for
      all nine UV filters. Identification and quantification of compounds was performed
      for lipophilic UV filters with gas chromatography-electroionisation-mass
      spectrometry and for polar and mid-polar compounds with liquid chromatography
      coupled to electrospray ionisation mass spectrometry. Instrumental detection
      limits (IDL) varied between 5 and 260 pg injected and method detection limits
      (MDL) were in the low ng/g lipids range for all test compounds. The described
      analytical methods are shown to be useful to screen for estrogenic UV filters in
      environmental samples such as fish and polar organic chemical integrative
      samplers.

PMID- 18632109
TI  - Ionic liquid-based dynamic liquid-phase microextraction: application to the
      determination of anti-inflammatory drugs in urine samples.
AB  - Dynamic liquid-phase microextraction (dLPME) using an ionic liquid as acceptor
      phase is proposed for the determination of six non-steroidal anti-inflammatory
      drugs (NSAIDs) in human urine samples for the first time. The extraction is
      carried out in a simple and automatic flow configuration. The chemical affinity
      between the extractant (1-butyl-3-methylimidazolium hexafluorophosphate) and the
      analytes permits a selective isolation of the drugs from the sample matrix
      allowing also their preconcentration. The whole analytical method has been
      optimized taking into account all the chemical, physical and hydrodynamic
      variables. The proposed method is a valuable alternative for the analysis of
      these drugs in urine within the concentration range 0.1-10 microg mL(-1),
      allowing their determination at therapeutic and toxic levels. Limits of detection
      were in the range from 38 ng mL(-1) (indomethacin) to 70 ng mL(-1) (naproxen).
      The repeatability of the proposed method expressed as RSD (n=5) varied between
      2.1% (flurbiprofen) and 3.8% (tolmetin).

PMID- 18632110
TI  - Solubilization of triglycerides in liquid crystals of nonionic surfactant.
AB  - The solubilization of triglycerides [1,2,3-tributanoylglycerol (TBG) and 1,2,3
      trihexanoylglycerol (THG)] in water/octa(oxyethylene) dodecyl ether (C(12)EO(8))
      systems has been investigated. Oil-induced changes in the structure of liquid
      crystals in water/C(12)EO(8) system have been studied by optical observation and
      small-angle X-ray scattering (SAXS) measurements. In the water/C(12)EO(8)/oil
      systems, solubilization of THG and TBG induces a transition between H(1)
      (hexagonal) and L(alpha) (lamellar) liquid crystals at high C(12)EO(8)
      concentrations, whereas at low surfactant concentrations a H(1)-I(1)
      (discontinuous micellar cubic phase) transition occurs. This anomalous behavior
      is attributed to the partitioning of solubilized oil in the micelles. At low
      surfactant concentrations THG is mainly solubilized into the hydrophobic cores of
      the surfactant micelles, indicating high swelling or low penetration tendency,
      resulting in a steep increase in the radius of the aggregates (r(H)), thereby
      inducing a rod-sphere transition. At high surfactant concentrations, THG is not
      mainly solubilized into the core but distributed between the palisade layer and
      the core of the aggregates. The TBG is considerably solubilized into the
      surfactant palisade layer, indicating a high penetration tendency, resulting in
      an increase in the effective cross-sectional area per surfactant molecule, a(s).
      The thermal stability of the I(1) phase increases with the solubilization of THG
      into the aggregate cores. The percentage deviation of the experimental interlayer
      spacings (P(d)) from complete swelling was also evaluated for different
      triglycerides in the H(1) and L(alpha) phases or different surfactant
      concentrations. It is found that the penetration tendency of triglycerides could
      be used as a tuning parameter for I(1) phase formation depending on the
      surfactant concentration and the molecular weight of the oil.

PMID- 18632111
TI  - Application of water-activated carbon isotherm models to water adsorption
      isotherms of single-walled carbon nanotubes.
AB  - The objective of this study is to understand the interactions of water with novel
      nanocarbons by implementing semiempirical models that were developed to interpret
      adsorption isotherms of water in common carbonaceous adsorbents. Water adsorption
      isotherms were gravimetrically determined on several single-walled carbon
      nanotube (SWNT) and activated carbon samples. Each isotherm was fitted to the
      Dubinin-Serpinsky (DS) equation, the Dubinin-Astakov equation, the cooperative
      multimolecular sorption theory, and the Do and Do equations. The applicability of
      these models was evaluated by high correlation coefficients and the significance
      of fitting parameters, especially those that delineate the concentration of
      hydrophilic functional groups, micropore volume, and the size of water clusters.
      Samples were also characterized by spectroscopic and adsorption techniques, and
      properties complementary to those quantified by the fitting parameters were
      extracted from the data collected. The comparison of fitting parameters with
      sample characterization results was used as the methodology for selecting the
      most informative and the best-fitting model. We conclude that the Do equation, as
      modified by Marban et al., is the most suitable semiempirical equation for
      predicting from experimental isotherms alone the size of molecular clusters that
      facilitate adsorption in SWNTs, deconvoluting the experimental isotherms into two
      subisotherms: adsorption onto hydrophilic groups and filling of micropores, and
      quantifying the concentration of hydrophilic functional groups, as well as
      determining the micropore volume explored by water. With the exception of the DS
      equation, the application of other water isotherm models to SWNTs is not
      computationally tractable. The findings from this research should aid studies of
      water adsorption in SWNTs by molecular simulation, which remains the most popular
      tool for understanding the microscopic behavior of water in nanocarbons.

PMID- 18632112
TI  - Use of intramyocardial conduction delay during early transmural ischemia to
      interpret electrocardiograms.

PMID- 18632113
TI  - Working memory in children: a time-constrained functioning similar to adults.
AB  - Within the time-based resource-sharing (TBRS) model, we tested a new conception
      of the relationships between processing and storage in which the core mechanisms
      of working memory (WM) are time constrained. However, our previous studies were
      restricted to adults. The current study aimed at demonstrating that these
      mechanisms are present and functional before adulthood. For this purpose, we
      investigated the effect on maintenance of the duration of the attentional capture
      induced by processing. In two experiments using computer-paced WM span tasks, 10
      year-olds were asked to maintain letters while performing spatial location
      judgments. The duration of this processing was manipulated by varying either the
      discriminability between target locations or the contrast between targets and
      background. In both experiments, longer processing times resulted in poorer
      recall, as we observed previously in adults. These findings suggest that the core
      mechanisms of WM described by the TBRS model are already settled during
      childhood.

PMID- 18632114
TI  - Intracellular mechanisms of specific beta-adrenoceptor antagonists involved in
      improved cardiac function and survival in a genetic model of heart failure.
AB  - beta-blockers, as class, improve cardiac function and survival in heart failure
      (HF). However, the molecular mechanisms underlying these beneficial effects
      remain elusive. In the present study, metoprolol and carvedilol were used in
      doses that display comparable heart rate reduction to assess their beneficial
      effects in a genetic model of sympathetic hyperactivity-induced HF
      (alpha(2A)/alpha(2C)-ARKO mice). Five month-old HF mice were randomly assigned to
      receive either saline, metoprolol or carvedilol for 8 weeks and age-matched wild
      type mice (WT) were used as controls. HF mice displayed baseline tachycardia,
      systolic dysfunction evaluated by echocardiography, 50% mortality rate, increased
      cardiac myocyte width (50%) and ventricular fibrosis (3-fold) compared with WT.
      All these responses were significantly improved by both treatments.
      Cardiomyocytes from HF mice showed reduced peak [Ca(2+)](i) transient (13%) using
      confocal microscopy imaging. Interestingly, while metoprolol improved [Ca(2+)](i)
      transient, carvedilol had no effect on peak [Ca(2+)](i) transient but also
      increased [Ca(2+)] transient decay dynamics. We then examined the influence of
      carvedilol in cardiac oxidative stress as an alternative target to explain its
      beneficial effects. Indeed, HF mice showed 10-fold decrease in cardiac
      reduced/oxidized glutathione ratio compared with WT, which was significantly
      improved only by carvedilol treatment. Taken together, we provide direct evidence
      that the beneficial effects of metoprolol were mainly associated with improved
      cardiac Ca(2+) transients and the net balance of cardiac Ca(2+) handling proteins
      while carvedilol preferentially improved cardiac redox state.

PMID- 18632115
TI  - Inferred motions of the S3a helix during voltage-dependent K+ channel gating.
AB  - The gating of voltage-dependent potassium channels is controlled by
      conformational changes in voltage sensor domains. Previous studies have shown
      that the S1 and the S2 helices of the voltage sensor are static with respect to
      motion across the membrane, while the voltage sensor paddle consisting of the C
      terminal half of S3 (S3b) and the charge-bearing S4 is mobile. The mobile
      component is attached to S1 and S2 via the S2-S3 turn and the N-terminal half of
      S3 (S3a). In this study, we analyze KvAP, an archaebacterial voltage-dependent
      potassium channel, to study the mobility with respect to translation across the
      membrane of S3a. We utilize an assay based on attachment of tethered biotin and
      its site-specific accessibility to avidin. Our results reveal that the S3a helix
      does not move appreciably across the membrane in association with gating. The
      static behavior of S3a constrains the conformations available to the voltage
      sensor when it closes and suggests that a set of negative countercharges within
      the membrane's inner leaflet remains intact in the closed conformation.

PMID- 18632116
TI  - AdcAII, a new pneumococcal Zn-binding protein homologous with ABC transporters:
      biochemical and structural analysis.
AB  - Regulation of metal homeostasis is vital for pathogenic bacteria facing drastic
      metal concentration changes in various locations within the host during invasion.
      Metal-binding receptors (MBRs), one of the extracellular components of ATP
      binding cassette transporters, have been shown to be essential in this process.
      Streptococcus pneumoniae expresses two characterized MBRs: PsaA and AdcA, two
      extracellular lipoproteins encoded by the psaABCD and adcRCBA operons,
      respectively. The Mn- and Zn-uptake functions of PsaA and AdcA, respectively,
      have been well established. Here we describe AdcAII as a third putative S.
      pneumoniae MBR. The analysis of a phylogenetic tree built from the sequence
      alignment of 68 proteins reveals a subgroup of members displaying an unusual
      genetic operon organisation. The adcAII gene belongs to a 6670-nucleotide-long
      transcript spanning the spr0903 to spr0907 loci encoding for the CcdA,
      thioredoxine, YfnA, AdcAII and PhtD proteins. Two adjacent repeats of imperfect
      AdcR-binding consensus sequence were identified upstream of the adcAII gene,
      suggesting a transcriptional co-regulation of adcAII and phtD genes. Biophysical
      and structural studies of recombinant AdcAII were performed to identify the metal
      specificity of the protein. Using electrospray mass spectrometry in native
      conditions, we found that Zn was bound to recombinant AdcAII. Screening of the
      effect of 10 cationic ions on the thermal stability of AdcAII revealed that Zn
      had the most pronounced stabilizing effect. The crystal structure of AdcAII has
      been solved to 2.4 A resolution. One Zn ion is bound to each AdcAII molecule in a
      symmetrical active site composed of three His and one Glu. The structure almost
      perfectly superimposed on the known MBR structures. The presence of a flexible 15
      residue-long loop close to the metal-binding site is specific to those
      specialized in Zn transport. Taken together, these functional and structural data
      provide new perspectives related to the physiological role of AdcAII in
      pneumococcus Zn homeostasis.

PMID- 18632117
TI  - Effective immunosuppressant therapy with cyclophosphamide and corticosteroids in
      paraneoplastic cerebellar degeneration.
AB  - Paraneoplastic cerebellar degeneration (PCD) is a rare immune mediated phenomenon
      often associated with cancer of the ovarian. Hitherto, tumor dissection is the
      mainstay in therapy while immunomodulatory treatment regimes often fail. Here we
      report on an 86 year old female patient who developed a severe pancerebellar
      syndrome. Clinical course, onconeural (anti-Yo) antibodies and detection of
      ovarian cancer suggest the assumption of PCD as the most probable diagnosis. We
      initiated a high-dose course of corticosteroids followed by a single dose of
      cyclophosphamide (600 mg/day). Surprisingly patient's condition improved and
      stabilized within days subsequent to cyclophosphamide application. This case
      demonstrates the benefit of immunosuppressive therapy in an anti-Yo positive
      patient with severe PCD secondary to an ovarian cancer.

PMID- 18632118
TI  - Comparative effects of herbicides on photosynthesis and growth of tropical
      estuarine microalgae.
AB  - Pulse amplitude modulation (PAM) fluorometry is ideally suited to measure the sub
      lethal impacts of photosystem II (PSII)-inhibiting herbicides on microalgae, but
      key relationships between effective quantum yield [Y(II)] and the traditional
      endpoints growth rate (micro) and biomass increase are unknown. The effects of
      three PSII-inhibiting herbicides; diuron, hexazinone and atrazine, were examined
      on two tropical benthic microalgae; Navicula sp. (Heterokontophyta) and
      Nephroselmis pyriformis (Chlorophyta). The relationships between Y(II), micro and
      biomass increase were consistent (r2 > or =0.90) and linear (1:1), validating the
      utility of PAM fluorometry as a rapid and reliable technique to measure sub
      lethal toxicity thresholds of PSII-inhibiting herbicides in these microalgae. The
      order of toxicity (EC50 range) was: diuron (16-33 nM) > hexazinone (25-110 nM) >
      atrazine (130-620 nm) for both algal species. Growth rate and photosynthesis were
      affected at diuron concentrations that have been detected in coastal areas of the
      Great Barrier Reef.

PMID- 18632120
TI  - Processing conflicting information: facilitation, interference, and functional
      connectivity.
AB  - When a conflict task involves congruent, neutral, and incongruent conditions, it
      is possible to examine facilitation (neutral vs. congruent) and interference
      (incongruent vs. neutral) components. Very few studies investigated the brain
      areas that are specifically involved in facilitation or interference. We used
      functional magnetic resonance imaging while participants performed a magnitude
      conflict task (the size congruity paradigm). We observed four findings: (1) while
      most of the brain areas that were activated by conflict tasks showed interference
      effects, the intraparietal sulcus was the only region activated for both
      interference and facilitation components. (2) Two groups of participants could be
      distinguished based on the pattern of anterior cingulate cortex (ACC) activity,
      one with classical facilitation (congruent<neutral), one with reverse
      facilitation. (3) Functional connectivity analysis of the areas that were
      modulated by the conflict task revealed an anterior cingulate - lateral
      prefrontal cortex network and a dorsal parietal - premotor cortex network. We
      suggest that the former plays a role in cognitive control and conflict detection,
      whereas the latter participates in top-down selection of task-relevant stimuli
      and response mapping. (4) These networks were modulated by the two groups that we
      distinguished based on the ACC activation.

PMID- 18632121
TI  - Flavonol pentaglycosides of Cordyla (Leguminosae: Papilionoideae: Swartzieae):
      distribution and taxonomic implications.
AB  - A survey of foliar flavonoids in the swartzioid legume genus Cordyla s.l.
      revealed that three species, C. haraka, C. pinnata and C. richardii, were rich in
      flavonol pentaglycosides. Their structures were elucidated by spectroscopic and
      chemical methods as the 3-O-alpha-L-rhamnopyranosyl(1-->3)-alpha-L
      rhamnopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->6)]-beta-D-galactopyranoside-7
      O-alpha-L-rhamnopyranosides of quercetin and kaempferol (cordylasins A and B,
      respectively). These compounds were not found in the remaining species, C.
      africana, C. densiflora, C. madagascariensis (two subspecies) and C. somalensis,
      which exhibited different profiles of flavonoid glycosides. The distribution of
      flavonol pentaglycosides in Cordyla s.l. does not support a recent proposal to
      place both C. haraka and C. madagascariensis in the genus Dupuya [Kirkbride,
      J.H., 2005. Dupuya, a new genus of Malagasy legumes (Fabaceae). Novon 15, 305
      314]. The generic relationship between Cordyla s.l. and Mildbraediodendron is
      also reassessed on the basis of chemical characters, as the O-linked
      tetrasaccharide that characterises cordylasins A and B is the same as that found
      in mildbraedin (kaempferol 3-O-alpha-l-rhamnopyranosyl(1-->3)-alpha-l
      rhamnopyranosyl(1-->2)[alpha-l-rhamnopyranosyl(1-->6)]-beta-D-galactopyranoside),
      the main foliar flavonoid of Mildbraediodendron excelsum. Mildbraedin itself was
      found to be a minor constituent of leaflet extracts of C. haraka, C. pinnata and
      C. richardii, and a major constituent of C. somalensis.

PMID- 18632119
TI  - Ischemic stroke and neurogenesis in the subventricular zone.
AB  - The subventricular zone (SVZ) of the lateral ventricle contains neural stem and
      progenitor cells that generate neuroblasts, which migrate to the olfactory bulb
      where they differentiate into interneurons. Ischemic stroke induces neurogenesis
      in the SVZ and these cells migrate to the boundary of the ischemic lesion. This
      article reviews current data on cytokinetics, signaling pathways and vascular
      niche that are involved in processes of proliferation, differentiation, and
      migration of neural progenitor cells after stroke.

PMID- 18632122
TI  - Glucuronoarabinoxylan structure in the walls of Aechmea leaf chlorenchyma cells
      is related to wall strength.
AB  - In CAM-plants rising levels of malic acid in the early morning cause elevated
      turgor pressures in leaf chlorenchyma cells. Under specific conditions this
      process is lethal for sensitive plants resulting in chlorenchyma cell burst while
      other species can cope with these high pressures and do not show cell burst under
      comparable conditions. The non-cellulosic polysaccharide composition of
      chlorenchyma cell walls was investigated and compared in three cultivars of
      Aechmea with high sensitivity for chlorenchyma cell burst and three cultivars
      with low sensitivity. Chlorenchyma layers were cut from the leaf and the non
      cellulosic carbohydrate fraction of the cell wall fraction was analyzed by gas
      liquid chromatography. Glucuronoarabinoxylans (GAXs) were the major non
      cellulosic polysaccharides in Aechmea. The fine structure of these GAXs was
      strongly related to chlorenchyma wall strength. Chlorenchyma cell walls from
      cultivars with low sensitivity to cell burst were characterized by an A/X ratio
      of ca. 0.13 while those from cultivars with high sensitivity showed an A/X ratio
      of ca. 0.23. Xylose chains from cultivars with high cell burst sensitivity were
      ca. 40% more substituted with arabinose compared to cultivars with low
      sensitivity for cell burst. The results indicate a relationship in vivo between
      glucuronoarabinoxylan fine structure and chlorenchyma cell wall strength in
      Aechmea. The evidence obtained supports the hypothesis that GAXs with low degrees
      of substitution cross-link cellulose microfibrils, while GAXs with high degrees
      of substitution do not. A lower degree of arabinose substitution on the xylose
      backbone implies stronger cell walls and the possibility of withstanding higher
      internal turgor pressures without cell bursting.

PMID- 18632123
TI  - Who smokes during pregnancy? An analysis of the German Perinatal Quality Survey
      2005.
AB  - OBJECTIVES: Smoking during pregnancy greatly increases the risk of adverse fetal
      outcomes. This study was conducted to investigate the prevalence of smoking
      during pregnancy and to identify social, behavioural and preventable perinatal
      risk factors. STUDY DESIGN: This study was based on a national registry, acquired
      in the 2005 German Perinatal Quality Survey, which contains data on 99.31% of
      deliveries in Germany. METHODS: The database draws on prenatal and perinatal data
      on 668,085 newborns and 647,392 mothers at 917 maternity clinics. Bivariate
      methods and multiple logistic regression analyses were used. RESULTS: Thirteen
      percent of pregnant women smoked at least one cigarette per day after becoming
      aware of their pregnancy. Median cigarette consumption among pregnant smokers was
      10 cigarettes per day. The prevalence of smoking was higher than average among
      women of low socio-economic status (20%), women without a partner (23%) and
      pregnant women under 20 years of age (34%). Multiparous women and women suffering
      from psychosocial stress smoked more than the respective reference groups. In
      addition, pregnant smokers displayed major deficits in terms of prenatal care.
      CONCLUSIONS: This study identified risk groups with above-average smoking
      prevalence during pregnancy. These risk groups are key target populations for
      preventive measures.

PMID- 18632124
TI  - Tuberculous infection in Saharia, a primitive tribal community of Central India.
AB  - A cross-sectional tuberculin survey was carried out to estimate the prevalence of
      tuberculous infection and the annual risk of tuberculosis infection (ARTI) among
      children of Saharia, a primitive ethnic group in Madhya Pradesh, Central India. A
      total of 1341 children aged 1-9 years were subjected to tuberculin testing with 1
      TU of PPD RT 23 and the reaction sizes were read after 72 h. The proportion of
      BCG scar-positive children was 34.6%. The frequency distribution of children by
      reaction sizes indicated a clear-cut anti-mode at 11 mm and a mode at 18 mm at
      the right-hand side of the distribution. The prevalence of infection among
      children irrespective of BCG scar was estimated as 20.4% (95% CI 18.2-22.5%) and
      the ARTI was 3.9% (95% CI 3.5-4.3%). The corresponding figures were 21.1% (95% CI
      18.3-23.8%) and 3.9% (95% CI 3.4-4.5%) among BCG scar-negative children and 19.0%
      (95% CI 15.4-22.5%) and 4.0% (95% CI 3.2-4.8%) among BCG scar-positive children.
      The findings of the present study show a high prevalence of tuberculous infection
      and high ARTI in this primitive ethnic group. There is an urgent need to further
      intensify tuberculosis control measures on a sustained and long-term basis in
      this area.

PMID- 18632125
TI  - Mass drug administration under the programme to eliminate lymphatic filariasis in
      Orissa, India: a mixed-methods study to identify factors associated with
      compliance and non-compliance.
AB  - The present study aimed to identify the factors responsible for compliance and
      non-compliance of mass drug administration (MDA) under the programme to eliminate
      lymphatic filariasis (LF) from Orissa, India. It was based on both quantitative
      (through household MDA coverage survey) and qualitative data (through semi
      structured interviews with heads of compliant and non-compliant households)
      collected during an MDA held in November 2005 in two districts of Orissa. In
      these districts, 83% of the eligible population received the drug (coverage) and
      only 49.5% people actually consumed the drug (compliance). Seventeen percent of
      the population did not even receive the drug. The predominant reason for not
      receiving the drug at household level was that the drug distributor did not visit
      the household, while the fear of adverse reactions is the predominant reason for
      not consuming it. The qualitative data revealed that the major contributor to
      taking the drug was the awareness that drug protects them from LF. Motivation by
      health workers was another reason for compliance. In many endemic areas, the
      issues related to non-compliance were taken casually during implementation.
      Hence, it is imperative to make the programme more efficient by addressing the
      issues linked to low compliance.

PMID- 18632126
TI  - Prevalence, intensity and risk factors for clonorchiasis and possible use of
      questionnaires to detect individuals at risk in northern Vietnam.
AB  - A high prevalence of the liver flukes Clonorchis sinensis and Opisthorchis
      viverrini has been reported in a number of provinces in Vietnam. Knowledge about
      C. sinensis infection gained from Thailand over the past decade suggests that the
      habit of eating raw freshwater fish is a major risk factor for infection.
      However, further information to confirm this is needed. In the present study 1155
      villagers in two communes in northern Vietnam were interviewed and their stools
      were examined for the presence of liver flukes. The prevalence of infection was
      26% and was 3.6 times higher in males than in females. The habit of eating raw
      fish increased the risk of C. sinensis infection 53-fold. These results provide
      evidence of a strong correlation between the intensity of C. sinensis infection
      and the cumulative quantity of freshwater fish consumed in a lifetime and suggest
      that simple questionnaires could be used in endemic areas to quickly identify
      populations at risk and enable targeted treatment.

PMID- 18632127
TI  - A new role for HIV nucleocapsid protein in modulating the specificity of plus
      strand priming.
AB  - The current study indicates a new role for HIV nucleocapsid protein (NC) in
      modulating the specificity of plus strand priming. RNase H cleavage by reverse
      transcriptase (RT) during minus strand synthesis gives rise to RNA fragments that
      could potentially be used as primers for synthesis of the plus strand, leading to
      the initiation of priming from multiple points as has been observed for other
      retroviruses. For HIV, the central and 3' polypurine tracts (PPTs) are the major
      sites of plus strand initiation. Using reconstituted in vitro assays, results
      showed that NC greatly reduced the efficiency of extension of non-PPT RNA
      primers, but not PPT. Experiments mimicking HIV replication showed that RT
      generated and used both PPT and non-PPT RNAs to initiate "plus strand" synthesis,
      but non-PPT usage was strongly inhibited by NC. The results support a role for NC
      in specifying primer usage during plus strand synthesis.

PMID- 18632128
TI  - The nucleoprotein and the viral RNA of infectious salmon anemia virus (ISAV) are
      localized in the nucleolus of infected cells.
AB  - The infectious salmon anemia virus (ISAV), which belongs to the new genus
      Isavirus of the Orthomyxoviridae family, is an important pathogen of the salmon
      farming industry. Indirect immunofluorescence assays carried out with monoclonal
      antibodies specific for the nucleoprotein (NP) reveal differential staining of
      sub-cellular compartments in infected cells. Particularly interesting was the
      staining of the nucleolus, which showed co-localization with nucleolin in CHSE
      214, EPC and SHK-1 cells infected with ISAV. These results were confirmed by co
      immunoprecipitation studies showing an interaction between NP and nucleolin. In
      addition, in situ hybridization carried out with probes specific for each of the
      8 RNA segments of ISAV showed that the genomic as well as the anti-genomic
      strands were also localized in the nucleolus. These results suggest a role of the
      nucleolus in the replication and/or in the packaging of the ISAV genome.

PMID- 18632129
TI  - Avian influenza virus isolated in wild waterfowl in Argentina: evidence of a
      potentially unique phylogenetic lineage in South America.
AB  - Avian influenza (AI) viruses have been sporadically isolated in South America.
      The most recent reports are from an outbreak in commercial poultry in Chile in
      2002 and its putative ancestor from a wild bird in Bolivia in 2001. Extensive
      surveillance in wild birds was carried out in Argentina during 2006-2007. Using
      RRT-PCR, 12 AI positive detections were made from cloacal swabs. One of those
      positive samples yielded an AI virus isolated from a wild kelp gull (Larus
      dominicanus) captured in the South Atlantic coastline of Argentina. Further
      characterization by nucleotide sequencing reveals that it belongs to the H13N9
      subtype. Phylogenetic analysis of the 8 viral genes suggests that the 6 internal
      genes are related to the isolates from Chile and Bolivia. The analysis also
      indicates that a cluster of phylogenetically related AI viruses from South
      America may have evolved independently, with minimal gene exchange, from
      influenza viruses in other latitudes. The data produced from our investigations
      are valuable contributions to the study of AI viruses in South America.

PMID- 18632130
TI  - An early function of the adenoviral E1B 55 kDa protein is required for the
      nuclear relocalization of the cellular p53 protein in adenovirus-infected normal
      human cells.
AB  - It is well established that the human subgroup C adenovirus type 5 (Ad5) E1B 55
      kDa protein can regulate the activity and concentration of the cellular tumor
      suppressor, p53. However, the contribution(s) of these functions of the E1B
      protein to viral reproduction remains unclear. To investigate this issue, we
      examined properties of p53 in normal human cells infected by E1B mutant viruses
      that display defective entry into the late phase or viral late mRNA export. The
      steady-state concentrations of p53 were significantly higher in cells infected by
      the E1B 55 kDa null mutant Hr6 or three mutants carrying small insertions in the
      E1B 55 kDa protein coding sequence than in Ad5-infected cells. Nevertheless, none
      of the mutants induced apoptosis in infected cells. Rather, the localization of
      p53 to E1B containing nuclear sites observed during infection by Ad5 was
      prevented by mutations that impair interaction of the E1B protein with p53 and/or
      with the E4 Orf6 protein. These results indicate that the E1B protein fulfills an
      early function that correlates efficient entry into the late phase with the
      localization of E1B and p53 in the nucleus of Ad5-infected normal human cells.

PMID- 18632131
TI  - Dissolved organic matter from treated effluent of a major wastewater treatment
      plant: characterization and influence on copper toxicity.
AB  - A combination of reverse osmosis (RO) concentration and DAX-8/XAD-4 resin
      adsorption techniques is used to isolate the various constituents of urban
      dissolved organic matter (DOM) from inorganic salts. Three fractions: hydrophobic
      (HPO), transphilic (TPI) and hydrophilic (HPI) accounting respectively for 35%,
      20% and 45% of extracted carbon, are isolated from effluents of a major French
      wastewater treatment plant. This atypical DOC distribution, in comparison with
      natural water where the HPO fraction dominates, shows the significance of HPI
      fraction which often gets neglected because of extraction difficulties. A number
      of analytical techniques (elemental, spectroscopic: UV, FTIR) allow highlighting
      the weak aromaticity of wastewater effluent DOM (EfOM) due to fewer degradation
      and condensation processes and the strong presence of proteinaceous structures
      indicative of intense microbial activity. Copper toxicity in the presence of DOM
      is estimated using an acute toxicity test on Daphnia Magna (Strauss). Results
      reveal the similar protective role of each EfOM fraction compared to reference
      Suwannee river fulvic acid despite lower EfOM aromaticity (i.e. specific UV
      absorbance). The environmental implications of these results are discussed with
      respect to the development of site-specific water quality criteria.

PMID- 18632132
TI  - PCDDs/PCDFs and dioxin-like PCBs: recent body burden levels and their
      determinants among general inhabitants in Japan.
AB  - OBJECTIVE: The objective was to grasp the recent body burden levels of
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs)
      and dioxin-like polychlorinated biphenyls (DL-PCBs) and to investigate their
      determinants among general inhabitants in Japan. METHODS: This study was
      performed on 1374 participants aged 15-73 years, who were not occupational
      exposure to PCDDs/PCDFs and DL-PCBs, living widely in 75 different residential
      areas of 25 prefectures in Japan. Seven PCDDs, ten PCDFs, twelve DL-PCBs, which
      are assigned a toxicity equivalent factor, and biochemical factors were
      determined in fasting blood. A questionnaire survey on life-style was also
      performed. RESULTS: The median of total toxicity equivalent (TEQ) was 20pgTEQ/g
      lipid. The TEQs of PCDDs/PCDFs, DL-PCBs and total TEQ increased with age. The
      intake frequency of fish-and-shellfish was positively associated with the TEQ of
      DL-PCBs in both sexes. Current smoking was negatively related to the TEQ of DL
      PCBs in male subjects but not in female subjects. Feeding status was
      significantly related to the TEQs of PCDDs/PCDFs, DL-PCBs and total TEQ, being
      lowest in breast feeding and highest in never and bottle feeding. According to
      the results of subgroup analysis, parity was not associated with the TEQs.
      CONCLUSIONS: The fish-and-shellfish consumption may contribute to the
      accumulation of DL-PCBs, and smoking may induce some biological action for the
      elimination of DL-PCBs from the human body. Breast feeding is considered to be
      one of the major excretory pathways of PCDDs/PCDFs and DL-PCBs in women, while
      parity may not largely contribute to the elimination of these pollutants.

PMID- 18632133
TI  - Discriminating the pH toxicity to Poecilia reticulata Peters, 1859 in the Dunas
      Lake (Camacari, BA, Brazil).
AB  - Toxic potential of the pH reduction to fingerlings of Poecilia reticulata,
      through acute toxicity bioassays, as well as the influence of increased pH on the
      toxicity were assessed. Acid lake samples (Dunas Lake) were collected during 19
      months, and assessed with following treatments: water at local pH (+/-3.0) and
      samples with modified pH to 3.5, 3.8, 4.0, 4.3, 4.6, 5.0, 5.5, 6.0, and 6.5.
      Culture water samples with pH reduced to 3.0 were also assessed. Newborn P.
      reticulata were exposed during 96h, and dead/immobile organisms were counted at
      various time intervals during exposure (short intervals in the beginning and long
      towards the end). Mean results of LT50 and confidence intervals from the Dunas
      Lake and control water with reduced pH were 1.36 (+/-0.48)h, and 1.03 (+/-0.50)h,
      respectively, with no statistical difference. Samples with increased pH showed a
      significant reduction in toxicity, with no toxicity detected at pH 6.0 and
      higher. Relationship between pH and lethal toxicity for fingerlings of P.
      reticulata demonstrated that pH exerted a strong effect on the survival of this
      species at the Dunas Lake, explaining about 80% of the toxicity observed.

PMID- 18632134
TI  - Characteristic behavior of peroxyacetyl nitrate (PAN) in Seoul megacity, Korea.
AB  - We measured the concentrations of peroxyacetyl nitrate (PAN) and other
      photochemically reactive species, including O3, NO2, and non-methane hydrocarbons
      (NMHCs), in the Seoul Metropolitan area (SMA) during May through June in 2004 and
      2005. PAN was determined using a fast chromatograph with luminol-based
      chemiluminescence detection. Mixing ratios of PAN ranged from below the detection
      limit (0.1ppbv) to 10.4ppbv with an average of 0.8ppbv. O3 concentrations ranged
      from 0 to 141ppbv. The average PAN/O3 ratio of 0.07 was higher than that observed
      in cities of Europe and North America (0.02) where control strategies have been
      enforced to reduce hydrocarbon emissions through extensively reformulated
      gasoline programs. Strong positive correlations between daily PAN and O3 maxima
      during the day demonstrate that similar photochemical factors controlled the
      production of these two chemicals. However, relationships between PAN and its
      precursors, NO2 and NMHCs, suggest that PAN production was more sensitive to NO2
      than NMHCs levels whereas O3 production was limited by the overall availability
      of NMHCs. It is likely that the compositions of NMHCs in SMA were favorable for
      PAN production because of the low fractions of oxygenated compounds in automobile
      fuels. PAN maxima were observed around noon, which was 2-3h earlier than the much
      broader O3 maxima that occurred in the midafternoon. After reaching the maximum,
      PAN concentrations rapidly dropped within a few hours, which could be largely due
      to thermal destruction and to limited production under the typically low NO2
      levels that occurred in the early afternoon. The heterogeneous destruction of
      particulate matter could be an additional sink for PAN in SMA.

PMID- 18632135
TI  - Detection of DNA damage in haemocytes of Mytilus galloprovincialis in the coastal
      ecosystems of Kastela and Trogir bays, Croatia.
AB  - Coastal waters are burdened with different contaminants of anthropogenic origin
      due to intensive urbanisation and economical development. Bays, semi-enclosed
      areas with limited water renewal ability, are particularly endangered by
      contaminant inputs. Kastela Bay (Dalmatia, Eastern Adriatic) has earlier been
      identified as an area loaded with diffuse sources of pollution, including
      genotoxic agents. However, there is lack of data on the effects of these
      contaminants on the local marine fauna. The aim of this study was to assess
      genotoxic impacts in Kastela Bay and the neighbouring Trogir Bay using the
      micronucleus test and Comet assay with mussel (Mytilus galloprovincialis)
      haemocytes. Native and caged mussels were included in the studies. Our results
      confirmed that mussels in Kastela and Trogir Bays are affected by genotoxic
      contaminants. In addition to mussels from the most known polluted site (Vranjic),
      there was evidence for genotoxic effects in mussels collected at other locations.
      The response in the micronucleus test and the Comet assay differed somewhat
      between sites, the latter apparently being more sensitive, but the two methods
      complement each other and it is therefore desirable to use them both in
      monitoring the impacts of genotoxic pollution in coastal waters.

PMID- 18632136
TI  - Evaluation of the use of human hair for biomonitoring the deficiency of essential
      and exposure to toxic elements.
AB  - Monitoring the nutritional status of essential elements and assessing exposure of
      individuals to toxic elements is of great importance for human health. Thus, the
      appropriate selection and measurement of biomarkers of internal dose is of
      critical importance. Due to their many advantages, hair samples have been widely
      used to assess human exposure to different contaminants. However, the validity of
      this biomarker in evaluating the level of trace elements in the human body is
      debatable. In the present study, we evaluated the relationship between levels of
      trace elements in hair and whole blood or plasma in a Brazilian population. Hair,
      blood and plasma were collected from 280 adult volunteers for metal
      determination. An ICP-MS was used for sample analysis. Manganese, copper, lead
      and strontium levels in blood varied from 5.1 to 14.7, from 494.8 to 2383.8, from
      5.9 to 330.1 and from 11.6 to 87.3 microg/L, respectively. Corresponding levels
      in hair varied from 0.05 to 6.71, from 0.02 to 37.59, from 0.02 to 30.63 and from
      0.9 to 12.6 microg/g. Trace element levels in plasma varied from 0.07 to 8.62,
      from 118.2 to 1577.7 and from 2.31 to 34.2 microg/L for Mn, Cu and Sr,
      respectively. There was a weak correlation (r=0.22, p<0.001) between lead levels
      in hair and blood. Moreover, copper and strontium levels in blood correlate with
      those levels in plasma (r=0.64 , p<0.001 for Cu) and (r=0.22, p<0.05 for Sr).
      However, for Cu, Mn and Sr there was no correlation between levels in hair and
      blood. Our findings suggest that while the idea of measuring trace elements in
      hair is attractive, hair is not an appropriate biomarker for evaluating Cu, Mn
      and Sr deficiency or Pb exposure.

PMID- 18632137
TI  - Influence of compost amendment on pyrene availability from artificially spiked
      soil to two subspecies of Cucurbita pepo.
AB  - The dissolved organic matter (DOM) fraction of soil organic matter (SOM) may
      positively contribute to polycyclic aromatic hydrocarbons (PAHs) bioavailability.
      This work investigated the effects of DOM-rich and PAHs-free compost amendment on
      the plant uptake of pyrene. Two subspecies of Cucurbita pepo (ssp. pepo cv. Raven
      and ssp. texana cv. Sunray) were grown for three weeks in a spiked soil
      containing 83.9 mg kg(-1) pyrene under four different treatments; inorganic
      fertilizer (IF) alone, 15% (v/v) mixed gardening compost with IF (MX15%+IF),
      MX30% alone, and no fertilization (NF). Equilibrium pyrene desorptions from a
      spiked soil (104 mg kg(-1)) under different concentrations (35-590 mg-C L(-1)) of
      DOM extracts derived from two types of composts including MX and cow manure were
      also conducted. After harvest, the decrease in the pyrene concentration of the
      soil ranged from 46-65% for the different treatments. The total dry biomass for
      both plants was highest under MX15%+IF. The bioconcentration factors of pyrene
      for both also tended to decrease with increasing MX dose from 15% to 30%.
      However, the total uptakes of pyrene with IF and MX15%+IF were not statistically
      different (36.7 and 33.7 microg for Raven, and 5.20 and 7.90 microg for Sunray,
      respectively). These values were around 100% higher than that with NF (17.4
      microg for Raven and 2.0 microg for Sunray). The pyrene desorption data confirmed
      the ability of DOM to associate with pyrene as indicated by its increase in
      apparent water solubility. On the basis of these results, MX application at 15%
      (v/v) does not significantly reduce the phytoextraction of pyrene due to the
      enhancement of plant growth as well as the possible contribution of DOM fractions
      to pyrene bioavailability. The application of compost may not pose serious
      concerns regarding the efficiency of phytoremediation of PAHs-polluted soil.

PMID- 18632138
TI  - Occurrence of endocrine-disrupting chemicals in indoor dust.
AB  - Human exposure to indoor dust enriched with endocrine-disrupting chemicals
      released from numerous indoor sources has been a focus of increasing concern.
      Longer residence times and elevated contaminant concentrations in the indoor
      environment may increase chances of exposure to these contaminants by 1000-fold
      compared to outdoor exposure. To investigate the occurrence of semi-volatile
      endocrine-disrupting chemicals, including PBDEs (polybrominated diphenyl ethers),
      PCBs (polychlorinated biphenyls), phthalates, pyrethroids, DDT
      (dichlorodiphenyltrichloroethane) and its metabolites, and chlordanes, indoor
      dust samples were collected from household vacuum cleaner bags provided by 10
      apartments and 1 community hall in Davis, California, USA. Chemical analyses show
      that all indoor dust samples are highly contaminated by target analytes measured
      in the present study. Di-(2-ethylhexyl)phthalate was the most abundant (104-7630
      microg/g) in all samples and higher than other target analytes by 2 to 6 orders
      of magnitude. PBDEs were also found at high concentrations (1780-25,200 ng/g).
      Although the use of PCBs has been banned or restricted for decades, some samples
      had PCBs at levels that are considered to be concerns for human health,
      indicating that the potential risk posed by PCBs still remains high in the indoor
      environment, probably due to a lack of dissipation processes and continuous
      release from the sources. Although the use of some PBDEs is being phased out in
      some parts of the U.S., this trend may apply to PBDEs as well. We can anticipate
      that exposure to PBDEs will continue as long as the general public keeps using
      existing household items such as sofas, mattresses, and carpets that contain
      PBDEs. This study provides additional information that indoor dust is highly
      contaminated by persistent and endocrine-disrupting chemicals.

PMID- 18632139
TI  - Assessing biological indicators for remediated anthropogenic urban soils.
AB  - Anthropogenic urban soils, including brownfield soils, are currently
      characterised and evaluated using mainly physico-chemical properties. Our
      objective was to determine if biological indicators could provide a more
      comprehensive soil quality assessment relative to sustainability, identifying
      contamination issues, and effectiveness of remediation strategies. Plant,
      invertebrate and microbial assays and functional processes were evaluated at 10
      brownfield/anthropogenic urban locations at different stages of remediation in
      northwest England. Extreme sites were discriminated on the basis of earthworm
      counts and a small number of indicators likely to be related to their activity.
      It was concluded that identifying a universally-applicable benchmark suite of
      biological indicators is very unlikely without considerable advancement of
      knowledge and technology.

PMID- 18632140
TI  - A simulation-aided factorial analysis approach for characterizing interactive
      effects of system factors on composting processes.
AB  - A simulation-aided 2-level factorial analysis approach is proposed to
      characterize the interactive effects of composting factors (i.e. temperature,
      moisture, oxygen content and initial biomass concentration) on composting
      processes. To screen the important effect factors when high-order interactions
      occur, normal probability plot is applied to the result analysis. The results
      show that the factors have various effects on the composting process in different
      stages. At the 24th hour, the factors do not show significant effects on the
      composting process. At the 72nd hour when the composting process reaches active
      stage, the factors have important effects on the composting process, and their
      interactive effects are also significant. At the 144th hour, temperature and
      oxygen content still have effects on the composting process, but not as
      significant as those at the active stage. These findings could be useful for
      guiding composting-process operation and management and developing associated
      control strategies in different composting stages.

PMID- 18632141
TI  - Predictive factors for intraoperative complications in semirigid ureteroscopy:
      analysis of 1235 ballistic ureterolithotripsies.
AB  - OBJECTIVES: To evaluate potential preoperative predictive factors for
      complications in ureteroscopic treatment of ureteral stones. METHODS: One
      thousand two hundred thirty-five semirigid ureteroscopies for ureteral stones
      were prospectively inserted in our database and analyzed for complications.
      Preoperative variables evaluated were as follows: age, gender, length of
      symptoms, previous extracorporeal shock wave lithotripsy (ESWL), associated
      urinary tract infection (UTI), stone location, and degree of hydronephrosis.
      Univariate analysis and multivariate logistic regression were conducted. RESULTS:
      Fifty-five (4.4%) procedures had complications. There were 8 ureteral
      perforations, 5 paraureteral stones, 2 ureteral avulsions, 5 mucosal eversions, 1
      urethral injury, and 34 mucosal tears. In univariate analysis, age (P = .000),
      gender (P = .002), previous ESWL (P = .047), stone size (P = .001), and location
      (P = .001) were predictors of complications. Gender (P = .012), previous in situ
      ESWL (P = .037), stone size (P = .025), and location (P = .019) remained
      predictors in multivariate logistic regression. CONCLUSIONS: Semirigid
      ureteroscopy is a safe procedure with few complications. Larger stones,
      proximally located (iliac vessels or above) with previous in situ ESWL in men are
      preoperative predictors for intraoperative complications.

PMID- 18632142
TI  - Elective laparoscopic partial nephrectomy in patients with tumors >4 cm.
AB  - OBJECTIVES: To assess the perioperative outcomes of elective laparoscopic partial
      nephrectomy to treat renal tumors in patients with tumor burdens > 4 cm compared
      with those with tumor burdens of < or = 4 cm. METHODS: A retrospective review of
      medical records was performed for all patients who had undergone laparoscopic
      partial nephrectomy for renal tumors from January 2000 to March 2005. The
      preoperative risk factors (ie, sex, age, American Society for Anesthesiologists
      score), perioperative course (ie, operative time, estimated blood loss, warm
      ischemia time, intraoperative and postoperative complications, transfusion rate,
      intraoperative biopsy of surgical margins, length of hospitalization), and
      pathologic outcomes (ie, tumor stage, type, and grade) were collected and
      compared between the patients in the 2 cohorts. RESULTS: Patients with larger
      tumors had significantly more complications (37.0% vs 21.8%, P = .039) and a
      significantly longer hospitalization (4.1 vs 3.0 days, P = .026). For those with
      malignant tumors > 4 cm compared with those with malignant tumors of < or = 4 cm,
      the complication rate was 33.3% and 11.6% (P = 0.006) and the length of
      hospitalization was 4.5 and 3.2 days (P = .055), respectively. No other
      differences were noted between the 2 groups stratified by tumor size.
      CONCLUSIONS: Laparoscopic partial nephrectomy is an oncologically feasible option
      for tumor burdens > 4 cm in the greatest dimension to provide a nephron-sparing
      option for patients in whom individually selected lesions can be isolated.

PMID- 18632143
TI  - Tumor heterogeneity in ovarian cancer as demonstrated by in vitro chemoresistance
      assays.
AB  - OBJECTIVE: Tumor heterogeneity has been demonstrated in solid tumors. In vitro
      assays were developed in an effort to predict in vivo tumor response to therapy.
      We compare the in vitro assay results from multiple synchronous tumor samples in
      primary and recurrent ovarian cancers. METHODS: 38 patients underwent surgery for
      primary (18) or recurrent (20) ovarian cancer. Two (22) or three (16) samples
      were obtained per patient and tested using the EDR assay (Oncotech, Inc.). The
      percentage of Extreme (E), Intermediate (I) and Low (L) drug resistance for each
      chemotherapy was compared between synchronous specimens. RESULTS: A total of 92
      samples were collected and 787 drug assays were performed. Tumor heterogeneity
      was seen in 22.4% of all cases, including 18.6% primary and 26.1% recurrent
      diseases (p=0.01). Two category differences (L vs. E) were seen in 4.1% primary
      and 11.3% recurrent cases (7.8% of all cases). Overall, an increased frequency in
      EDR was seen in recurrent disease as compared to primary for all agents tested
      (22.9% primary vs. 31.6% recurrent, p=0.006). Marked heterogeneity of the drug
      resistance profiles was seen with paclitaxel as compared with
      cisplatin/gemcitabine (p=0.03), taxotere (p=0.04) or topotecan (p=0.04). No
      association was demonstrated between assay results and clinicopathologic
      parameters collected in this cohort. CONCLUSIONS: Treatment failure is often
      attributed to the development of chemoresistance. These results suggest that
      tumor heterogeneity may play an equally important role in treatment failure.
      Recurrent lesions exhibit greater heterogeneity and more frequent EDR. These data
      can influence therapeutic strategy i.e., multiple samples, sequential, or
      consolidation therapy.

PMID- 18632144
TI  - Ovarian follicular development and hormone concentrations in inseminated dairy
      cows with resynchronized estrous cycles.
AB  - The objective was to investigate ovarian follicular development and hormone
      concentrations in previously inseminated cows with estrous cycles resynchronized
      with various resynchronization treatments. Lactating dairy cows were treated with
      a previously used intravaginal progesterone releasing device (IVD) for 7 d
      (EB+IVD 7+EB, n=15) or 8 d (EB+IVD 8+EB, n=16), starting 13 d (Day 13) after a
      first estrus (Day 0) and AI. Estradiol benzoate (EB; 1 mg im) was given at device
      insertion and 24 h after removal. Other cows were given the same treatment as the
      EB+IVD 8+EB cows, but were not treated with EB at IVD insertion (IVD 8+EB, n=11).
      There were no differences (P>0.05) between EB+IVD 7+EB and EB+IVD 8+EB treatments
      for follicle dynamics and plasma progesterone concentrations during treatment.
      Based on a comparison between the IVD 8+EB treated cows and the pooled results of
      the EB+IVD 7+EB and EB+IVD 8+EB treated cows, EB at device insertion increased
      the number of follicular waves between Days 13 and 20 (mean+/-S.E.M.; 2.3+/-0.14
      vs 2.7+/-0.10, P=0.033), delayed emergence of follicles that were dominant or
      emerging on Day 20 (17.2+/-0.36 vs 14.1+/-0.65 d, P<0.001), reduced diameters of
      dominant or emerging follicles on Day 20 (9.0+/-0.58 vs 12.7+/-0.59, P<0.001),
      and reduced plasma progesterone concentrations by 0.85+/-0.44 ng/mL (P=0.059)
      during treatment. Furthermore, comparison of the IVD 8+EB to the EB+IVD 8+EB
      treated cows demonstrated that treatment with EB at device insertion also reduced
      the diameter of ovulatory follicles (14.2+/-0.58 vs 19.0+/-0.71 mm, P=0.001),
      delayed emergence of ovulatory follicles (17.0+/-0.32 vs 13.5+/-1.26, P=0.020),
      and reduced the interval from emergence to ovulation (7.0+/-0.32 vs 10.5+/-1.26
      d, P=0.020). We concluded that administration of EB altered ovarian follicular
      dynamics and tended to reduce plasma progesterone concentrations during treatment
      with an IVD that was used to resynchronize estrous cycles. However, use of a 7-d
      compared to an 8-day treatment with an IVD did not significantly affect follicle
      dynamics nor plasma progesterone concentrations during treatment.

PMID- 18632145
TI  - Experimental antimicrobial orthodontic adhesives using nanofillers and silver
      nanoparticles.
AB  - OBJECTIVES: Experimental composite adhesives (ECAs) containing silica nanofillers
      and silver nanoparticles were compared with two conventional adhesives (composite
      and resin-modified glass ionomer [RMGI]) to analyze surface characteristics,
      physical properties and antibacterial activities against cariogenic streptococci.
      METHODS: Surface roughness and surface free energy (SFE) characteristics were
      measured using confocal laser scanning microscopy and the sessile drop method.
      Shear bond strength and bond failure interface were analyzed to compare the
      physical properties. Antimicrobial activities were analyzed by a bacterial
      adhesion assay, a disk diffusion test, and an optical density measurement of
      bacterial suspension containing each adhesive. RESULTS: ECAs had rougher surfaces
      than conventional adhesives due to the addition of silver nanoparticles. ECAs had
      more similar SFE characteristics to composite than to RMGI. Bacterial adhesion to
      ECAs was less than to conventional adhesives, which was not influenced by saliva
      coating. Bacterial suspension containing ECAs showed slower bacterial growth than
      those containing conventional adhesives. There was no significant difference in
      shear bond strength and bond failure interface between ECAs and conventional
      adhesives. SIGNIFICANCE: This study suggests that ECAs can help prevent enamel
      demineralization around their surfaces without compromising physical properties.

PMID- 18632146
TI  - Effect of sintering time on biaxial strength of zirconium dioxide.
AB  - OBJECTIVES: Aim of this study was to evaluate effect of sintering time on
      mechanical properties of yttrium partially stabilized zirconia (Y-TZP) (ICE
      Zirkon, ZirkonZahn, Italy). METHODS: Fifty-six zirconia discs were divided into
      two groups. Discs of the first group were sintered in sintering oven (ZirkonZahn)
      at 20-1500 degrees C temperature using rise time of 3 h and kept at 1500 degrees
      C for 2 h. Discs of the second group were sintered at 20-1500 degrees C using
      rise time of 1h 40 min and kept at 1500 degrees C for 1 h. Half of the discs
      (n=15) from both groups were thermocycled in distilled water for 20000 cycles (5
      55 degrees C). Biaxial flexural strength of the discs (diameter 19.0 mm,
      thickness 1.6 mm) were measured dry at room temperature. Surface microhardness
      (VHN) was also measured. X-Ray diffraction analysis was performed to evaluate the
      ratio of tetragonal to monoclinic phase in thermocycled discs. The data was
      calculated using Weibull and ANOVA analysis. RESULTS: No statistically
      significant difference (p>0.05) was found between the groups in terms of
      sintering time or thermocycling. The biaxial flexural strength of the groups
      varied from 995MPa to 1127MPa. Surface microhardness varied from 1478 to 1532.
      The relative amount of the monoclinic phase was higher when zirconia was
      thermocycled and stored in water compared to control discs, which had no
      monoclinic phase at all. SIGNIFICANCE: Variation in the sintering time from 1.6h
      to 3.0 h did not influence mechanical properties of Y-TZP zirconia.

PMID- 18632148
TI  - Are withdrawal trials in paediatric rheumatic disease helpful?

PMID- 18632147
TI  - Abatacept in children with juvenile idiopathic arthritis: a randomised, double
      blind, placebo-controlled withdrawal trial.
AB  - BACKGROUND: Some children with juvenile idiopathic arthritis either do not
      respond, or are intolerant to, treatment with disease-modifying antirheumatic
      drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the
      safety and efficacy of abatacept, a selective T-cell costimulation modulator, in
      children with juvenile idiopathic arthritis who had failed previous treatments.
      METHODS: We did a double-blind, randomised controlled withdrawal trial between
      February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45
      centres, who had a history of active juvenile idiopathic arthritis; at least five
      active joints; and an inadequate response to, or intolerance to, at least one
      disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of
      abatacept intravenously in the open-label period of 4 months. Of the 170 patients
      who completed this lead-in course, 47 did not respond to the treatment according
      to predefined American College of Rheumatology (ACR) paediatric criteria and were
      excluded. Of the patients who did respond to abatacept, 60 were randomly assigned
      to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a
      flare of the arthritis, and 62 were randomly assigned to receive placebo at the
      same dose and timing. The primary endpoint was time to flare of arthritis. Flare
      was defined as worsening of 30% or more in at least three of six core variables,
      with at least 30% improvement in no more than one variable. We analysed all
      patients who were treated as per protocol. This trial is registered, number
      NCT00095173. FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients
      who were given placebo and 12 of 60 (20%) abatacept patients during the double
      blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for
      patients given placebo (insufficient events to calculate IQR); insufficient
      events had occurred in the abatacept group for median time to flare to be
      assessed (p=0.0002). The risk of flare in patients who continued abatacept was
      less than a third of that for controls during that double-blind period (hazard
      ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of
      adverse events did not differ in the two treatment groups. Adverse events were
      recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients
      (p=0.47); only two serious adverse events were reported, both in controls
      (p=0.50). INTERPRETATION: Selective modulation of T-cell costimulation with
      abatacept is a rational alternative treatment for children with juvenile
      idiopathic arthritis. FUNDING: Bristol-Myers Squibb.

PMID- 18632149
TI  - Biodegradable injectable polyurethanes: synthesis and evaluation for orthopaedic
      applications.
AB  - Biodegradable polyurethanes offer advantages in the design of injectable or
      preformed scaffolds for tissue engineering and other medical implant
      applications. We have developed two-part injectable prepolymer systems
      (prepolymer A and B) consisting of lactic acid and glycolic acid based polyester
      star polyols, pentaerythritol (PE) and ethyl lysine diisocyanate (ELDI). This
      study reports on the formulation and properties of a series of cross linked
      polyurethanes specifically developed for orthopaedic applications. Prepolymer A
      was based on PE and ELDI. Polyester polyols (prepolymer B) were based on PE and
      dl-lactic acid (PEDLLA) or PE and glycolic acid (PEGA) with molecular weights 456
      and 453, respectively. Several cross linked porous and non-porous polyurethanes
      were prepared by mixing and curing prepolymers A and B and their mechanical and
      thermal properties, in vitro (PBS/37 degrees C/pH 7.4) and in vivo (sheep bi
      lateral) degradation evaluated. The effect of incorporating beta-tricalcium
      phosphate (beta-TCP, 5 microns, 10 wt.%) was also investigated. The cured
      polymers exhibited high compressive strength (100-190 MPa) and modulus (1600-2300
      MPa). beta-TCP improved mechanical properties in PEDLLA based polyurethanes and
      retarded the onset of in vitro and in vivo degradation. Sheep study results
      demonstrated that the polymers in both injectable and precured forms did not
      cause any surgical difficulties or any adverse tissue response. Evidence of new
      bone growth and the gradual degradation of the polymers were observed with
      increased implant time up to 6 months.

PMID- 18632150
TI  - Iron-overload after autologous hematopoietic cell transplantation.

PMID- 18632151
TI  - Is JAK2 V617F mutation more than a diagnostic index? A meta-analysis of clinical
      outcomes in essential thrombocythemia.
AB  - A systematic review and meta-analysis was carried out to compare the frequency of
      clinically significant outcomes between JAK2 V617F positive and wild type
      patients with essential thrombocythemia (ET). JAK2 V617F positivity in patients
      with ET was associated with a clear increase in the odds of thrombosis [OR=1.83
      (95% CI, 1.32-2.53), p<0.0001], and much higher odds of transformation to
      polycythemia vera [OR=7.67 (95% CI, 2.04-28.87), p=0.0009]. The mean difference
      of the white blood cell count between JAK2 positive and negative patients was
      associated with an increased odds ratio for thrombosis (p=0.02). The JAK2 V617F
      mutation in patients with ET is associated with an increased risk of adverse
      cardiovascular outcomes via an increase in the leukocyte count.

PMID- 18632152
TI  - Myelofibrosis with myeloid metaplasia: the advanced phase of an untreated
      disseminated hematological cancer. Time to change our therapeutic attitude with
      early upfront treatment?
AB  - Myelofibrosis with myeloid metaplasia (MMM) is the end stage of the Philadelphia
      negative chronic myeloproliferative disorders, the classical clinical phenotype
      being featured by leukoerythroblastic anemia, bone marrow fibrosis and
      enlargement of the spleen and liver. In the early prefibrotic phase a proportion
      of the patients may be wrongly classified as having essential thrombocythemia
      (ET). Some patients with ET may also develop polycythemia vera (PV) and without a
      history of phlebotomies patients with primary myelofibrosis (PMF) are
      indistinguishable from those patients developing myelofibrosis during the course
      of polycythemia vera. Studies of the JAK2-mutational burden have yielded solid
      support to the concept of a biological continuum from JAK2-positive "ET" to JAK2
      positive PMF. The statement is presented that MMM is the advanced stage of an
      untreated disseminated hematological cancer which accordingly should be treated
      upfront when the disease presents in the very early stage as ET and PV, and when
      the cancer stem cells - the clonal CD34+ cells - have still not egressed from the
      bone marrow ("carcinoma in situ"). Based upon most recent studies showing that
      alpha-interferon is able to induce complete and sustained molecular remissions in
      patients with PV it is argued that we have to change our therapeutic attitude
      from a "wait and watch strategy" to early upfront treatment of ET and PV. In the
      "metabolic syndrome" normalisation of elevated blood glucose levels has been a
      very important therapeutic strategy to decrease the risk of thrombotic
      complications consequent to in vivo platelet-, granulocyte and endothelial cell
      activation, which are also considered of utmost importance for the development of
      thrombosis in ET and PV patients. Normalisation of elevated blood cell counts in
      the early phase of the "chronic myeloproliferative syndromes" - ET and PV -
      should be the therapeutic target in the future using alpha-interferon as
      monotherapy or in combination with conventional (hydroxyurea and anagrelide) and
      novel agents (JAK2-inhibitors). By this strategy preliminary reports in PV
      patients of minimal residual disease with normalisation of the bone marrow during
      long-term alpha-interferon treatment may be further substantiated in larger
      series of patients, hopefully being followed by a reduction in the risk of
      thrombohemorrhagic complications and ultimately the development of severe bone
      marrow fibrosis and myeloid metaplasia.

PMID- 18632153
TI  - Galanin: a potential role in mesolimbic dopamine-mediated instrumental behavior.
AB  - The involvement of the neuropeptide galanin in the consumption of the primary
      "commodities" of food and water is well established. However, the present review
      describes anatomical and behavioral evidence that suggests that galanin may also
      modulate ascending mesolimbic dopamine function and thereby play an inhibitory
      role in the systems by which instrumental behavior is energized toward acquiring
      primary commodities. General anatomical frameworks for this interaction are
      presented and future studies that could evaluate it are discussed.

PMID- 18632154
TI  - Improving police response to persons with mental illness: a multi-level
      conceptualization of CIT.
AB  - The large numbers of people with mental illness in jails and prisons has fueled
      policy concern in all domains of the justice system. This includes police
      practice, where initial decisions to involve persons in the justice system or
      divert them to mental health services are made. One approach to focus police
      response in these situations is the implementation of Crisis Intervention Teams
      (CIT). The CIT model is being implemented widely, with over 400 programs
      currently operating. While the limited evidence on CIT effectiveness is
      promising, research on CIT is limited in scope and conceptualization-much of it
      focusing on officer characteristics and training. In this paper we review the
      literature on CIT and present a conceptual model of police response to persons
      with mental illness that accounts for officer, organizational, mental health
      system and community level factors likely to influence implementation and
      effectiveness of CIT and other approaches. By moving our conceptualizations and
      research in this area to new levels of specificity, we may contribute more to
      effectiveness research on these interventions.

PMID- 18632155
TI  - Sensitization to wasp venom does not induce autoantibodies leading to
      infertility.
AB  - Antigenic cross-reactivity has been described between the venom allergen (antigen
      5) and mammalian testis proteins. Based on an allergen database we have
      previously shown that allergens can be represented by allergen motifs. A motif
      group was found containing venom antigen 5 sequences from different vespids.
      Using an optimized amino acid profile based on antigen 5 sequences for searching
      cross-reactive proteins, three human semen proteins belonging to the family of
      cysteine-rich secretory proteins (hCRISP) were found in the Swiss Protein
      database. To analyze antigenic cross-reactivity between antigen 5 and hCRISPs,
      antigen 5 from yellow jacket venom (Ves v 5) and two hCRISPs (CRISP-2 and -3)
      were chosen and produced as recombinant proteins in E. coli. A correlation was
      found between antibodies reacting with rVes v 5 and rhCRISP-2, -3 in a small
      human sera population indicating the presence of cross-reactive antibodies in
      human serum. Using intravenous immunoglobulin (IVIg), a therapeutic multidonor
      IgG preparation, cross-reactive antibodies were isolated that recognize rVes v 5,
      hCRISP-2 and -3 suggesting the presence of common epitopes between Ves v 5 and
      hCRISPs. However this cross-reactivity seems not to be linked to allergy to wasp
      venom as we could show no correlation between increasing CAP-class IgE level to
      wasp venom and IgG to sperm extract and hCRISPs. These data suggest that higher
      sensitization to wasp venom does not induce more antibodies against autoantigens
      and might not represent a higher risk to develop autoantibodies leading to
      infertility.

PMID- 18632156
TI  - Cloning, expression, and characterization of a single-domain antibody fragment
      with affinity for 15-acetyl-deoxynivalenol.
AB  - A single-domain variable heavy chain (V(H)H) antibody fragment specific to the
      mycotoxin 15-acetyldeoxynivalenol (15-AcDON) was obtained after immunization of a
      llama (Llama glama) with the protein conjugate 15-DON-BSA plus TiterMax Classic
      adjuvant. After confirmation of a polyclonal response to DON toxin in both
      conventional (cIgG) and heavy chain antibody (HCAb) fractions, a V(H)H library
      was constructed from amplified cDNA by nested PCR. V(H)H fragments with binding
      affinity for the mycotoxin were selected by panning of the phagemid library
      against microtiter plates coated with 15-DON-OVA. The dominant clone (NAT-267)
      was expressed in E. coli and was purified as a V(H)H monomer (mNAT-267) at a
      final concentration of 1.3 mg mL(-1). Isolated NAT-267 V(H)H DNA was fused to the
      homopentamerization domain of the B subunit of verotoxin to generate the
      pentabody format of single-domain antibody (sAb). The V(H)H pentamer (pNAT-267)
      was expressed in E. coli and was purified at a final concentration of 1.0 mg mL(
      1). Surface plasmon resonance (SPR) analysis of soluble mNAT-267 binding kinetics
      to immobilized 15-DON-Horse Radish Peroxidase (HRP) indicated a dissociation
      constant (K(D)) of 5microM. Competitive direct enzyme-linked immunosorbent assay
      (CD-ELISA) and fluorescence polarization assay (FPA) inhibition experiments with
      monomer and pentamer confirmed binding to 15-AcDON. Competitive inhibition FPAs
      with mNAT-267 and pNAT-267 determined IC(50) values of 1.24 and 0.50 microM,
      respectively, for 15-AcDON hapten. These values were similar to the IC(50) value
      of 1.42 microM for 15-AcDON given by polyclonal llama serum sampled 56 days after
      immunization. Competition formats for structurally related trichothecenes
      resulted in no cross-reactivity to: DON; 3-acetyldeoxynivalenol (3-AcDON);
      neosolaniol (NEO); diacetoxyscirpenol (DAS); and T-2 toxin. Our study confirmed
      that recombinant V(H)H fragments capable of binding low molecular weight haptens
      can be produced through the creation and panning of hyper-immunized single-domain
      (sdAb) libraries.

PMID- 18632157
TI  - A novel functional motif of osteopontin for human lymphocyte migration and
      survival.
AB  - Osteopontin (OPN) is an extracellular matrix protein of pleiotropic properties
      and plays an important role in regulating lymphocyte adhesion and cytokine
      production associated with inflammatory processes and autoimmune diseases. Here
      we developed and characterized a monoclonal antibody (mAbs) (23C3D3) specific for
      human OPN. This antibody could inhibit OPN-induced lymphocyte adhesion, migration
      and survival. Epitope mapping showed that 23C3D3 could specifically recognize the
      phage displayed peptide (43)WLNPDP(48). In addition, a synthesized mimetic
      peptide (mimotope) 23P ((40)VATWLNPDPSQK(51)) could block the binding of 23C3D3
      to hOPN and significantly inhibit the hOPN-induced lymphocyte adhesion, migration
      and survival. Moreover, mutations on the WLNPDP motif of hOPN also markedly
      diminished its activity for lymphocyte activation. Interestingly, this novel
      epitope is located in the extremely retained domain in all species. The
      functioning assay indicates that this novel epitope is critically involved in the
      lymphocyte migration and survival through activating ERK and the transcription
      factor NF-kappaB pathway, which can be inhibited by the motif (43)WLNPDP(48)
      blocking antibody, 23C3D3. These results suggest that this novel epitope of OPN
      may provide a potential therapeutic target for the treatment of T cell-mediated
      immune diseases.

PMID- 18632158
TI  - Genetic interactions of KIR and G1M immunoglobulin allotypes differ in obese from
      non-obese individuals with type 2 diabetes.
AB  - We analyzed the natural killer cell immunoglobulin-like receptor (KIR) genes and
      immunoglobulin allotypes in the development of type 2 diabetes (T2D) based on
      body mass index (BMI) measurements (obese vs. non-obese) in Puerto Rican
      Americans. Genetic interactions between the KIR haplotype A homozygotes (HAH) and
      its fraction containing two inhibitory receptors 2DL3 and 2DL1 and the activating
      receptor 2DS4 with immunoglobulin allotypes were studied. We found a significant
      association between the HAH and T2D (p=0.002; OR=7.97) and its interaction with
      the immunoglobulin allotype z: GM f/f (-) (p=<0.0001; OR, not determined) only in
      non-obese individuals. This association were due to the interactions between the
      2DL3/2DL3, 2DL1/2DL1, and 2DS4 fragment with GM f/f (-) in T2D patients
      (p=0.0017; OR=3.45). Analysis based on BMI demonstrated associations in both
      obese (p=0.037; OR=2.43; 95% CI=0.97-6.31) and non-obese individuals (p=<0.0001;
      OR=8.38; 95% CI=2.49-29.31). By contrast, the interaction of the GM allotype f/f
      (-) with the HAH fragment was associated with T2D only in non-obese individuals
      (p=<0.0001; OR=18.2; 95% CI=3.71-113.4). As expected, interaction of both HAH and
      its fragment with HLA-C group's ligands were significant. We used informative
      short tandem repeats (STRs) that distinguish major populations to determine
      genetic admixture and found that there was no genetic stratification in our
      cohort. Our findings are consistent with the possibility of an autoimmune and/or
      innateimmune component in the pathogenesis of T2D: NK receptors with chronic
      inflammation in obese and genetic interactions with G1M allotype in T2D non-obese
      possibly mediating autoimmunity.

PMID- 18632159
TI  - Novel organotypic culture model of adult mammalian neurosensory retina in co
      culture with retinal pigment epithelium.
AB  - PURPOSE: The purpose of this study was to assess survival of adult mammalian
      neurosensory retina cultured in contact with the layer of a choroid-retinal
      pigment epithelium (RPE) explant. METHODS: The entire adult porcine neurosensory
      retina and RPE-choroid layer were placed in tissue culture by juxtaposing both
      tissues in their original orientation. Culture of the neurosensory retina alone
      and freshly prepared retina were used as control. After 3 days in culture retinal
      explants were fixed and processed for immunohistochemistry and TUNEL technique.
      RESULTS: We observed limited nuclei loss and significant reduction in apoptotic
      cells in nuclear cell layers (GCL, INL, and ONL) and decreased Muller cell
      hypertrophy in retina-RPE cultures compared to retinal cultures alone. In
      addition, cultures were characterized by reduced upregulation of GFAP, vimentin
      as well as S100 and increased glutamine synthetase expression. CONCLUSIONS: As
      any tissue culture model, retinal tissue culture is a short-term system and since
      degenerative processes begin quite early it may be a good model to investigate
      degenerative processes in the retina. However, our model of culture of retina
      adjacent to the RPE-choroid layer improves the maintenance of neural retina as
      evidenced by reduced apoptosis in nuclear cell layers (GCL, INL, and ONL) and
      reduced gliosis as indicated by the diminished expression of glial-specific
      proteins and increased glutamine synthetase compared to cultures of retina alone.
      Thus the retina-RPE-choroid culture system can enable the evaluation of
      interactions between RPE and neural retina, the role of signaling molecules as
      well the effect of pharmaceuticals on retinal biology.

PMID- 18632160
TI  - The prognosis of undetected depression in older general practice patients. A one
      year follow-up study.
AB  - BACKGROUND: Late-life depression often remains undetected in primary care.
      However, as there is evidence that GPs do identify those with the most severe and
      persistent disorders, it is important to know more about the prognosis of
      depressive disorders that are not detected by GPs. METHODS: A one-year follow-up
      study of depressed patients of 55 years and older consulting their GP in The
      Netherlands. A two-stepped screening procedure was used to diagnose depression
      using the GDS-15 and PRIME-MD. GPs and patients were not informed about the
      results. The course of depression was measured with the MADRS and PRIME-MD, at
      six and twelve months. Remission was defined by no longer fulfilling DSM-criteria
      for depressive disorder and a MADRS-score below 10. The prognosis of those not
      detected by GPs was compared to those that were detected. RESULTS: 73 patients
      were followed for one year. Among the 49 (67%) patients that were not detected by
      their GP as being depressed, 33% had remitted after one year. Of the 24 (33%)
      depressed patients that were detected by their GP, 37% had remitted after one
      year. Detected patients tended to have more serious depression and more comorbid
      anxiety than undetected patients. CONCLUSIONS: Although GPs identify older
      depressed patients who are most in need of treatment, the prognosis of patients
      that go undetected is poor.

PMID- 18632161
TI  - Long-term outcomes of youth who manifested the CBCL-Pediatric Bipolar Disorder
      phenotype during childhood and/or adolescence.
AB  - OBJECTIVE: Recent studies have identified a Child Behavior Checklist (CBCL)
      profile that characterizes children with severe aggression, inattention, and mood
      instability. This profile has been coined the CBCL-Pediatric Bipolar Disorder
      (PBD) phenotype, because it is commonly seen among children with bipolar
      disorder. However, mounting evidence suggests that the CBCL-PBD may be a better
      tool for identifying children with severe functional impairment and broad-ranging
      psychiatric comorbidities rather than bipolar disorder itself. No studies have
      followed individuals with the CBCL-PBD profile through adulthood, so its long
      term implications remain unclear. The present authors examined diagnostic and
      functional trajectories of individuals with the CBCL-PBD profile from early
      childhood through young adulthood using data from a longitudinal high-risk study.
      METHOD: Participants (n=101) are part of a 23-year study of youth at risk for
      major mood disorder who have completed diagnostic and functional assessments at
      regular intervals. RESULTS: Across development, participants with the CBCL-PBD
      phenotype exhibited marked psychosocial impairment, increased rates of suicidal
      thoughts and behaviors and heightened risk for comorbid anxiety, bipolar
      disorder, cluster B personality disorders and ADHD in young adulthood, compared
      to participants without this presentation. However, diagnostic accuracy for any
      one particular disorder was found to be low. CONCLUSIONS: Children with the CBCL
      PBD profile are at risk for ongoing, severe, psychiatric symptomatology including
      behavior and emotional comorbidities in general, and bipolar disorder, anxiety,
      ADHD, cluster B personality disorders in particular. However, the value of this
      profile may be in predicting ongoing comorbidity and impairment, rather than any
      one specific DSM-IV diagnosis.

PMID- 18632162
TI  - How myasthenia gravis alters the safety factor for neuromuscular transmission.
AB  - Myasthenia gravis (MG), the most common of autoimmune myasthenic syndromes, is
      characterized by antibodies directed against the skeletal muscle acetylcholine
      receptors (AChRs). Endplate Na(+) channels ensure the efficiency of neuromuscular
      transmission by reducing the threshold depolarization needed to trigger an action
      potential. Postsynaptic AChRs and voltage-gated Na(+) channels are both lost from
      the neuromuscular junction in MG. This study examined the impact of postsynaptic
      voltage-gated Na(+) channel loss on the safety factor for neuromuscular
      transmission. In intercostal nerve-muscle preparations from MG patients, we found
      that endplate AChR loss decreases the size of the endplate potential, and
      endplate Na(+) channel loss increases the threshold depolarization needed to
      produce a muscle action potential. To evaluate whether AChR-specific antibody
      impairs the function of Na(+) channels, we tested omohyoid nerve-muscle
      preparations from rats injected with monoclonal myasthenogenic IgG (passive
      transfer model of MG [PTMG]). The AChR antibody that produces PTMG did not alter
      the function of Na(+) channels. We conclude that loss of endplate Na(+) channels
      in MG is due to complement-mediated loss of endplate membrane rather than a
      direct effect of myasthenogenic antibodies on endplate Na(+) channels.

PMID- 18632163
TI  - Suppression of experimental autoimmune myasthenia gravis by combination therapy:
      pentoxifylline as a steroid-sparing agent.
AB  - Myasthenia gravis (MG) is frequently treated by corticosteroids such as
      methylprednisolone. However, continuous treatment with steroids often results in
      adverse effects. In the present study we evaluated the therapeutic potential of a
      combination of suboptimal doses of methylprednisolone (Solumedrol) and
      Pentoxifylline (PTX), a general phosphodiesterase (PDE) inhibitor, in rat
      experimental autoimmune MG (EAMG). This combined treatment resulted in a
      pronounced suppressive effect on EAMG and was by far more effective than each of
      the drugs administered separately at these low doses. The suppressive effect on
      EAMG was accompanied by decreased humoral and cellular responses to AChR as well
      as down-regulated mRNA expression levels of Th1 cytokines and IL-10 in lymph node
      cells and of PDE-4 and cathepsin-l in the muscle. This study demonstrates the
      potential of PTX as a steroid-sparing agent in the management of myasthenia
      gravis.

PMID- 18632164
TI  - Myasthenia gravis sera have no effect on cardiomyocytes in vitro.
AB  - Myasthenia gravis (MG) is an autoimmune disorder primarily caused by circulating
      autoantibodies targeting the nicotinic acetylcholine receptor. Several studies
      have suggested a link between MG and heart disease. Girardi heart cells were
      treated with MG sera, measuring cytotoxic effects using flow cytometry, adenylate
      kinase (AK) release and evaluating morphology. MG sera did not induce
      morphological changes in the cells. AK release from cells treated with MG sera
      did not exceed controls and flow cytometric examination did not reveal any
      increase in dead or apoptotic cells. We conclude that MG sera have no cytotoxic
      effect in our heart cell culture system.

PMID- 18632165
TI  - The genetics of clinical outcome in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a common inflammatory disease of the central nervous
      system (CNS), the clinical course of which varies considerably between patients.
      Genetic complexity and interactions with as yet unknown environmental factors
      have hindered researchers from fully elucidating the aetiology of the disease. In
      addition to influencing disease susceptibility, epidemiological evidence suggests
      that genetic factors may affect phenotypic expression of the disease. Genes that
      affect clinical outcome may be more effective therapeutic targets than those
      which determine susceptibility. We present in this review a comprehensive survey
      of the genes (both MHC- and non-MHC-related) that have been investigated for
      their role in disease outcome in MS. Recent studies implicating the role of the
      genotype and epistatic interactions in the MHC in determining outcome are
      highlighted.

PMID- 18632166
TI  - Difficult intubation due to undiagnosed congenital tracheal web.
AB  - Congenital tracheal web is a rare anomaly, usually misdiagnosed as asthma or
      chronic obstructive lung diseases. Clinical suspicion and appropriate diagnostic
      imaging combined with endoscopic examinations are the mainstay approach. Symptoms
      of stridor, dyspnea and recurrent lower airway infections are the most common
      clinical presentations. We report a case of difficult intubation in a child due
      to an undiagnosed congenital tracheal web.

PMID- 18632167
TI  - Identification and characterization of two novel cytosolic sulfotransferases,
      SULT1 ST7 and SULT1 ST8, from zebrafish.
AB  - Cytosolic sulfotransferases (SULTs) constitute a family of Phase II
      detoxification enzymes that are involved in the protection against potentially
      harmful xenobiotics as well as the regulation and homeostasis of endogenous
      compounds. Compared with humans and rodents, the zebrafish serves as an excellent
      model for studying the role of SULTs in the detoxification of environmental
      pollutants including environmental estrogens. By searching the expressed sequence
      tag database, two zebrafish cDNAs encoding putative SULTs were identified.
      Sequence analysis indicated that these two putative zebrafish SULTs belong to the
      SULT1 gene family. The recombinant form of these two novel zebrafish SULTs,
      designated SULT1 ST7 and SULT1 ST8, were expressed using the pGEX-2TK glutathione
      S-transferase (GST) gene fusion system and purified from transformed BL21 (DE3)
      cells. Purified GST-fusion protein form of SULT1 ST7 and SULT1 ST8 exhibited
      strong sulfating activities toward environmental estrogens, particularly
      hydroxylated polychlorinated biphenyls (PCBs), among various endogenous and
      xenobiotic compounds tested as substrates. pH-dependence experiments showed that
      SULT1 ST7 and SULT1 ST8 displayed pH optima at 6.5 and 8.0, respectively. Kinetic
      parameters of the two enzymes in catalyzing the sulfation of catechin and
      chlorogenic acid as well as 3-chloro-4-biphenylol were determined. Developmental
      expression experiments revealed distinct patterns of expression of SULT1 ST7 and
      SULT1 ST8 during embryonic development and throughout the larval stage onto
      maturity.

PMID- 18632168
TI  - Use of changes in B-type natriuretic peptides to detect ischemia in selected
      patients.
AB  - BACKGROUND: There is accumulating evidence that transient exercise-induced
      ischemia triggers the release of B-type natriuretic peptide (BNP) and N-terminal
      pro-B-type natriuretic peptide (NT-proBNP). The aim of this study was to either
      confirm or refute a previous investigation suggesting that myocardial ischemia
      can reliably be detected by exercise-induced changes in BNP or NT-proBNP levels
      in selected patients. METHODS: A total of 139 consecutive patients with normal
      left ventricular function and normal resting BNP and NT-proBNP levels referred
      for rest/stress myocardial perfusion single-photon emission computed tomography
      (SPECT) were analyzed. Levels of BNP and NT-proBNP were determined before and
      immediately after symptom-limited bicycle ergometry. RESULTS: Inducible
      myocardial ischemia on perfusion images was detected in 46 patients (33%). Median
      exercise-induced increases in BNP (DeltaBNP) and NT-proBNP (DeltaNT-proBNP) were
      similar in patients with and without inducible ischemia (DeltaBNP 12.7 pg/ml vs.
      9.4 pg/ml, p=0.109; DeltaNT-proBNP 7 pg/ml vs. 6 pg/ml, p=0.309). The area under
      the receiver operating characteristic curve for the ability to detect myocardial
      ischemia was 0.583 (95% CI, 0.479-0.688) for DeltaBNP, and 0.553 (95% CI, 0.450
      0.656) for DeltaNT-proBNP. CONCLUSIONS: Exercise-induced changes in BNP and NT
      proBNP do not reliably detect myocardial ischemia in selected patients.

PMID- 18632169
TI  - Maternal complication of pregnancy in Marfan syndrome.
AB  - OBJECTIVES: Evaluate the risk of aortic complications (aortic dissection or
      prophylactic aortic surgical replacement) associated with pregnancy in Marfan
      syndrome in the absence of specific care. BACKGROUND: Data are scarce on aortic
      complications during pregnancy in Marfan syndrome. METHODS: Retrospective study
      on a large population (415 patients) followed up in our multidisciplinary out
      patient clinic devoted to Marfan syndrome. Women over 18 years of age were
      divided into 2 groups: 85 had been pregnant (MFSP+) giving birth to 136 children
      through 160 pregnancies; 68 had not been pregnant (MFSP-). The occurrence of
      aortic complication was compared between the 2 groups using a piecewise discrete
      time model. RESULTS: In MFSP+, 7 aortic complications occurred during 160
      pregnancies (4.4%) and 17 aortic complications occurred during 1870 years of
      follow-up out of pregnancy. In MFSP-, 14 aortic complications occurred over 940
      years of follow-up. Pregnancy was associated with a 5 fold increase in risk of
      aortic complication, which did not translate into increased risk during life,
      suggesting that pregnancy may act as a revealer in women prone to aortic
      complication. CONCLUSIONS: Pregnancy is associated with a transient increased
      risk of aortic complication in the absence of specific care.

PMID- 18632170
TI  - Primary malignant pericardial sarcoma.
AB  - We describe the case of a 91-year-old man who presented with a large pericardial
      effusion and an intrapericardial mass. Primary malignant pericardial sarcoma was
      diagnosed by percutaneous pericardial tumor biopsy. The patient died of multiple
      organ failure three months later. We also review the epidemiology, clinical
      presentation, pathology and treatment of cardiac tumors. The prognosis of primary
      malignant pericardial sarcoma is very poor especially in old people.

PMID- 18632171
TI  - Management of pregnant women with cardiac diseases at potential risk of
      thromboembolism--experience and review.
AB  - Over a 7-year period, the chart records of six pregnant women with cardiac
      diseases at potential risk of thromboembolism were reviewed. All six patients
      survived and recovered well eventually. LMWH and beta-adrenergic blocker were
      effective to deal with atrial fibrillation. Digitalis and dobutamine were
      beneficial to prevent heart failure resulted from degenerated porcine valve and
      dilated cardiomyopathy. In a patient with mechanical mitral valve, low-dose
      warfarin did not cause fetal malformation, and was effective to prevent thrombus
      formation. Protamine sulfate was safely administered to neutralize intravenous
      heparin effect before vaginal delivery. Life-threatening postpartum pulmonary
      hemorrhage occurred as a result of pulmonary hypertension with an aberrant right
      pulmonary artery, absolutely necessitating a long-term cardiopulmonary bypass
      resuscitation. Patient with primary pulmonary hypertension gave birth safely with
      forceps assistance under epidural anesthesia. From literatures reviewed and
      successful experiences presented here, prenatal correction of the underlying
      cardiac malformation, precise switch of anticoagulant administration, optimizing
      cardiac function, early delivery prior to heart failure, postpartum fluid
      restriction, minimized peripartum blood loss, and meticulously intensive cares
      are essential to achieve satisfactory outcomes.

PMID- 18632172
TI  - Kounis syndrome secondary to amoxicillin/clavulanic acid use in a child.
AB  - The concurrence of acute coronary syndromes with allergic or hypersensitivity as
      well as with anaphylactic or anaphylactoid reactions is increasingly encountered
      in clinical practice and there are several reports associating mast cell
      activation with acute cardiovascular events in adults. It was first described by
      Kounis as "allergic angina syndrome" progressing to "allergic myocardial
      infarction". The main mechanism proposed is the vasospasm of coronary arteries.
      This condition has not been described in childhood. We present a 13-year-old boy,
      admitted to our hospital with thoracic pain, 30 min after the ingestion of an
      oral dose of 500 mg of amoxicillin/clavulanic acid.

PMID- 18632173
TI  - Acute ST segment elevation myocardial infarction after sulbactam-ampicilllin
      induced anaphylactic shock in an adult with significant coronary artery disease:
      a case report.
AB  - Myocardial injury may complicate allergic reactions caused by several
      medications. We evaluated a case of a myocardial injury with transient ST segment
      elevation in a 72 year-old man presenting with collapse caused by sulbactam
      ampicilllin assumption. The purpose of this report is to present this interesting
      case and revise the classification of Kounis syndrome.

PMID- 18632174
TI  - Presence and potential for horizontal transfer of antibiotic resistance in
      oxidase-positive bacteria populating raw salad vegetables.
AB  - To assess whether domestically grown fresh salad vegetables constitute a possible
      reservoir of antibiotic resistance for Canadian consumers, aerobic bacteria
      capable of forming colonies at 30 degrees C on nutrient-limited media were
      recovered from a single sampling of Romaine lettuce, Savoy spinach and alfalfa
      sprouts, then examined for their susceptibility to ten antibiotics and the
      carriage of potentially mobile R-plasmids and integrons. Of the 140 isolates
      resistant to one or more antibiotic, 93.5 and 90.0% were resistant to ampicillin
      and cephalothin; 35.7% to chloramphenicol, 10.0% to streptomycin, 4.2% to
      nalidixic acid, 4.2% to kanamycin, and 2.8% to gentamicin. Gram-positive isolates
      accounted for less than 4% of the antibiotic resistant strains. A small portion
      (23.1%) of the predominant oxidase-positive, gram-negative isolates was resistant
      to two or more antimicrobials. Members of the Pseudomonas fluorescens/putida
      complex were most prevalent among the 34 resistant strains identified.
      Sphingobacterium spp. and Acinetobacter baumanni also were detected. Ten of 52
      resistant strains carried plasmids, 3 of which were self-transmissible and bore
      resistance to ampicillin and kanamycin. Eighteen of 48 gave PCR evidence for
      integron DNA. Class 2 type integrons were the most prevalent, followed by class
      1. We conclude that the foods examined here carry antibiotic resistant bacteria
      at the retail level. Further, our determination that resistant strains contain
      integron-specific DNA sequences and self-transmissible R-plasmids indicates their
      potential to influence the pool of antibiotic resistance in humans via lateral
      gene transfer subsequent to ingestion.

PMID- 18632175
TI  - Carbon nanotubes based optical immunodetection of Staphylococcal Enterotoxin B
      (SEB) in food.
AB  - Staphylococcal enterotoxins (SEs) are a major cause of food-borne diseases,
      traditionally SEs assayed immunologically with ELISA. Carbon nanotubes' (CNT)
      unique mechanical and electronic properties combined with a large specific
      surface area make them attractive for biosensing. To investigate whether CNT
      could improve the sensitivity of ELISA assays, we developed an optical CNT
      immunosensor for the detection of Staphylococcal Enterotoxin B (SEB) in food.
      Anti-SEB antibodies were immobilized onto a CNT surface through electrostatic
      adsorption and then the antibody-nanotube mixture was bound onto a polycarbonate
      film. SEB was then detected by a "sandwich-type" ELISA assay on the polycarbonate
      film. The use of CNT increased the sensitivity of the immunosensor by at least 6
      fold, lowering the detection limit of SEB. The CNT immunosensor was also able to
      detect SEB various foods, suggesting the utility of CNT for this and other
      optical-based immunological detection methods.

PMID- 18632176
TI  - Phosphorylation of the TGBp1 movement protein of Potato virus X by a Nicotiana
      tabacum CK2-like activity.
AB  - The movement protein (MP) TGBp1 of the potexvirus Potato virus X (PVX) is a
      multifunctional protein required for cell-to-cell movement within the host plant.
      Recent work on other plant viruses has indicated that MP phosphorylation by host
      kinases can regulate MP function. In this study, we demonstrate that recombinant
      and native TGBp1 are phosphorylated by Nicotiana tabacum extracts from both PVX
      infected and non-infected leaves. The phosphorylation activity present in plant
      extracts has distinctive characteristics of casein kinase 2 (CK2): it is
      inhibited by heparin, stimulated by polylysine, and uses either ATP or GTP as
      phosphoryl donors. We also demonstrate that TGBp1 is efficiently phosphorylated
      by recombinant tobacco CK2 alpha subunit and by partially purified tobacco CK2.
      Phosphopeptide mass mapping reveals that TGBp1 is phosphorylated in Ser-165,
      which is localized within a CK2 consensus sequence. Our results strongly suggest
      that a N. tabacum kinase of the CK2 family is involved in TBGp1 phosphorylation
      during the course of viral infection.

PMID- 18632177
TI  - A peptide-based carrier for intracellular delivery of proteins into malignant
      glial cells in vitro.
AB  - Aiming at identification of novel peptides that can be employed for effective
      targeting of malignant gliomas, we used a 12-mer peptide phage display library
      and cultured human malignant glioma cells for phage selection. Several common
      phage clones emerged after 4 rounds of biopanning against the U87MG glioblastoma
      cell line. The most abundant phage clone VTW, expressing a sequence of
      VTWTPQAWFQWV, bound to U87MG cells 700-fold more efficiently than the original
      unselected library. The VTW phage also bound strongly to other human glioma cell
      lines, including H4, SW1088 and SW1783, but very weakly to normal human
      astrocytes and SV40-immortalized human astroglial cells. When compared to other
      non-glial tumor cells, the phage showed 400- to 1400-fold higher binding
      efficiency for U87MG cells. After linked to positively charged lysine peptides,
      the VTW peptide became water soluble and was able to deliver biologically active,
      hydrophilic beta-galactosidase into U87MG cells, with up to 90% of the cells
      being stained intensively blue. This peptide carrier did not show obvious protein
      delivery activities in the human astrocytes. Our results provide a proof of
      principle to the concept that peptides identified through phage display
      technology can be used to develop protein carriers that are capable of mediating
      intracellular delivery of hydrophilic macromolecules in a tumor cell-specific
      manner.

PMID- 18632178
TI  - Influence of Lys656Asn polymorphism of leptin receptor gene on insulin resistance
      in patients with diabetes mellitus type 2.
AB  - This is a descriptive study in diabetic patients. Mutant type patient (39%)
      (Lys656/Asn656 or Asn656/Asn656) group had higher fat mass, HOMA, CRP and leptin
      than wild type. Adiponectin levels were lower in mutant type group than wild type
      (61%) (Lys656/Lys656).

PMID- 18632179
TI  - Association of serum apolipoprotein B48 level with the presence of carotid plaque
      in type 2 diabetes mellitus.
AB  - AIMS: The atherogenicity of chylomicron remnants has been discussed. We examined
      whether serum apoB48 level is associated with the presence of carotid plaque in
      type 2 diabetic patients. METHOD: Forty type 2 diabetic patients (21 males and 19
      females, 52.8+/-11.8 years old; mean+/-S.D.) were divided into two groups by the
      presence or absence of carotid plaque. The diurnal change of serum apoB48 level
      was measured by enzyme-linked immunosorbent assay. RESULTS: Fasting serum apoB48
      level was higher in the subjects with carotid plaque than those without (6.5+/
      3.8vs. 4.1+/-1.9 microg/ml, p=0.01). Age- and gender-adjusted analysis showed
      that the presence of carotid plaque was associated with fasting apoB48 (OR 1.43;
      95% CI, 1.07-2.09, p=0.04) and triglyceride (OR 1.14; 95% CI, 1.02-1.32, p=0.04)
      levels. In normal LDL-cholesterol (<140 mg/dl) subjects, the presence of carotid
      plaque was associated with fasting apoB48 level (OR 2.16; 95% CI, 1.22-5.32,
      p=0.04), but not associated with fasting triglyceride level (OR 1.11; 95% CI,
      0.99-1.30, p=0.13). CONCLUSIONS: Serum apoB48 level was strongly associated with
      the presence of carotid plaque in type 2 diabetic patients.

PMID- 18632180
TI  - Aggravation of albuminuria by metabolic syndrome in type 2 diabetic Asian
      subjects.
AB  - AIMS: We investigated the relationship of urinary albumin excretion (UAE) to
      metabolic syndrome and type 2 diabetes in Asian. METHODS: A total of 446 subjects
      (187 without diabetes and 259 with type 2 diabetes) were enrolled in this study.
      The components of metabolic syndrome, high sensitivity C-reactive protein (hs
      CRP) and UAE were assessed. Based on metabolic syndrome and diabetes status,
      participants were categorized into one of the following groups: neither metabolic
      syndrome nor diabetes (MS-DM-), metabolic syndrome without diabetes (MS+DM-),
      diabetes without metabolic syndrome (MS-DM+) and both metabolic syndrome and
      diabetes (MS+DM+). RESULTS: The UAE in the MS+DM- group was higher than that in
      the MS-DM- group (P<0.001) and lower than that in the MS+DM+ group (P<0.001), but
      not significantly different from that in the MS-DM+ group (P=0.349). The trend of
      increasing UAE in these four groups was independent of hs-CRP. CONCLUSION: UAE
      was lowest in subjects with neither metabolic syndrome nor diabetes and highest
      in subjects with both metabolic syndrome and type 2 diabetes; however, there was
      no significant difference between the metabolic syndrome alone group and the type
      2 diabetes alone group.

PMID- 18632181
TI  - Weekly docetaxel vs. docetaxel-based combination chemotherapy as second-line
      treatment of advanced non-small-cell lung cancer patients. The DISTAL-2
      randomized trial.
AB  - BACKGROUND: Doublet chemotherapy is more effective than single-agent as first
      line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable
      information instead is available on the effect of doublets in second line
      treatment. The aim of DISTAL-2 study was to compare two doublets containing
      docetaxel with single agent docetaxel as second line treatment of patients with
      NSCLC (ClinicalTrials.gov id.:.NCT00345059). METHODS: NSCLC patients, aged <75,
      PS 0-2, who had failed platinum-based chemotherapy, were randomly assigned with a
      3:1:1 ratio to: arm A, weekly docetaxel (33.3mg/m(2) on days 1, 8, 15 q 4 weeks);
      arm B, weekly docetaxel (30 mg/m(2) on days 1, 8, 15) plus gemcitabine (800
      mg/m(2) on days 1, 8 q 4 weeks) or plus vinorelbine (20mg/m(2) on days 1, 8 q 4
      weeks) depending on which of the two had been used in first line; arm C, weekly
      docetaxel (as in arm B) plus capecitabine (625 mg/m(2) twice daily on days 5-18 q
      4 weeks). Primary end-point was overall survival (OS). Two comparisons were
      planned: arm B vs. A and arm C vs. A. Overall, 375 patients had to be randomized.
      Response was assessed by RECIST, quality of life (QoL) by EORTC questionnaires.
      RESULTS: 84 patients were randomized from May 2005 to December 2006, when the
      trial was prematurely stopped due to the slow accrual. After 62 deaths, median OS
      was 40.0 weeks in arm A, 32.6 weeks in arm B (p=0.18 vs. A) and 39.7 weeks in arm
      C (p=0.90 vs. A). Response rate was 6.4, 16.7 and 5.3%, and median progression
      free survival was 12.4, 13.1 and 11.9 weeks, for arms A, B and C, respectively.
      Patients in arm B had significantly more grade 3-4 haematological and non
      haematological toxicity compared to arm A, and patients in arm C had
      significantly more grade 3-4 non-haematological toxicity compared to arm A. No
      relevant differences were found in QoL analysis, with the exception of
      significant worsening in appetite, vomiting and hemoptysis for patients in arm B.
      CONCLUSION: Due to early termination, the trial does not have the planned
      statistical power. However, available data do not support the role of docetaxel
      based combination chemotherapy as second line in advanced NSCLC.

PMID- 18632182
TI  - Changes in contaminant mass discharge from DNAPL source mass depletion:
      evaluation at two field sites.
AB  - Changes in contaminant fluxes resulting from aggressive remediation of dense
      nonaqueous phase liquid (DNAPL) source zone were investigated at two sites, one
      at Hill Air Force Base (AFB), Utah, and the other at Ft. Lewis Military
      Reservation, Washington. Passive Flux Meters (PFM) and a variation of the
      Integral Pumping Test (IPT) were used to measure fluxes in ten wells installed
      along a transect down-gradient of the trichloroethylene (TCE) source zone, and
      perpendicular to the mean groundwater flow direction. At both sites, groundwater
      and contaminant fluxes were measured before and after the source-zone treatment.
      The measured contaminant fluxes (J; ML(-2)T(-1)) were integrated across the well
      transect to estimate contaminant mass discharge (M(D); MT(-1)) from the source
      zone. Estimated M(D) before source treatment, based on both PFM and IPT methods,
      were approximately 76 g/day for TCE at the Hill AFB site; and approximately 640
      g/day for TCE, and approximately 206 g/day for cis-dichloroethylene (DCE) at the
      Ft. Lewis site. TCE flux measurements made 1 year after source treatment at the
      Hill AFB site decreased to approximately 5 g/day. On the other hand, increased
      fluxes of DCE, a degradation byproduct of TCE, in tests subsequent to remediation
      at the Hill AFB site suggest enhanced microbial degradation after surfactant
      flooding. At the Ft. Lewis site, TCE mass discharge rates subsequent to
      remediation decreased to approximately 3 g/day for TCE and approximately 3 g/day
      for DCE approximately 1.8 years after remediation. At both field sites, PFM and
      IPT approaches provided comparable results for contaminant mass discharge rates,
      and show significant reductions (>90%) in TCE mass discharge as a result of DNAPL
      mass depletion from the source zone.

PMID- 18632183
TI  - Investigation of an outbreak of Enterobacter cloacae in a neonatal unit and
      review of the literature.
AB  - Enterobacter cloacae has emerged as an important pathogen in neonatal units, with
      several outbreaks of infection being reported. The aim of this study was to
      investigate an outbreak of sepsis due to E. cloacae in a neonatal unit and to
      review the literature. A retrospective cohort study was conducted in which cases
      were compared with all newborns hospitalised for more than 48h in the neonatal
      intensive care unit (NICU). Cohorting of infected patients and work
      reorganisation were implemented. Pulsed-field gel electrophoresis was performed.
      The retrospective cohort included the six cases and 13 control patients that had
      been in the NICU during April 2006. Univariate analysis showed that the use of
      dobutamine was significantly associated with infection (P=0.036) and that enteral
      feeding was a protective factor (P=0.02). Multivariate analysis did not find any
      independent risk factor. Bed occupancy rate in March 2006 was 109.6%, indicating
      overcrowding. PFGE identified indistinguishable patterns among isolates from all
      six newborns. PubMed and OVID was search from 1 January 1983 to 15 January 2008
      for papers including the terms 'E. cloacae', 'outbreaks', 'clusters' in
      combination with 'neonate', 'newborn', and 'infant'. We found 26 reports of
      outbreaks due to E. cloacae in neonate patients: sixteen (52%) were bloodstream
      infection outbreaks, of which two (12.5%) were related to multiple-dose
      medications. The source for our outbreak was not identified. Reinforcement of
      hygiene practices, restrictions on new admissions and the establishment of single
      dose medications helped to control the outbreak.

PMID- 18632185
TI  - Bloodstream infections caused by multidrug-resistant Enterobacteriaceae: report
      from two Portuguese hospitals.

PMID- 18632184
TI  - Effect of antibiotics on the bacterial load of meticillin-resistant
      Staphylococcus aureus colonisation in anterior nares.
AB  - Prevalence of hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA)
      infection or colonisation has been associated with antimicrobial consumption. The
      impact of antibiotic treatment on nasal colonisation is unknown. We conducted a
      three-month prospective study of 116 patients with extranasal MRSA infection or
      colonisation, whose nasal MRSA bacterial loads were determined during and after
      various antibiotic courses over a period of three weeks. Environmental swabs were
      also taken from the near patient environment. Concomitant nasal MRSA carriage was
      observed in 76.7% of extranasal MRSA-colonised or -infected patients. The median
      nasal MRSA bacterial load increased significantly from 2.78 (range 0-6.15) to
      5.30 (range 2.90-8.41) log(10) cfu per swab (cfu/swab) (P<0.001) over 21 days
      during beta-lactam therapy. It also increased from 0 (range 0-4.00) to 4.30
      (range 0-7.46) log(10)cfu/swab (P=0.039) over 14 days during fluoroquinolone
      therapy. Median bacterial loads were significantly higher for beta-lactam- and
      fluoroquinolone-treated patients on day 7 [4.78, range 0-7.30], day 14 [4.30,
      range 0-7.60] and day 21 [5.30, range 2.90-8.41] than controls not receiving
      antibiotics (P<0.05). These loads then decreased by 2-5log(10)cfu/swab 2 weeks
      after discontinuation of antibiotics. The environment of patients receiving beta
      lactam agents (relative risk: 3.55; 95% confidence interval: 1.30-9.62; P=0.018)
      or fluoroquinolones (4.32; 1.52-12.31; P=0.008) demonstrated more MRSA
      contamination than the environment around control patients (0.79; 0.67-0.93;
      P=0.002). Patients on beta-lactam or fluoroquinolone therapy have increased
      incidence of MRSA colonisation and higher nasal bacterial loads, and appear to
      spread their MRSA into the near patient environment.

PMID- 18632187
TI  - Abdominal compression effectively increases the size of the common femoral vein,
      as measured by ultrasonography.
AB  - STUDY OBJECTIVE: We determine the effect of abdominal compression on common
      femoral vein cross-sectional area. The effects of Valsalva maneuver and reverse
      Trendelenburg's position are also studied. METHODS: Prospective, observational,
      comparative evaluation performed on sequential patients presenting to an adult
      emergency department. Using ultrasonography, common femoral vein area was
      measured with patients in supine and reverse Trendelenburg's positions. In each
      position measurements were taken at baseline while abdominal compression was
      performed and while the patient performed the Valsalva maneuver. Abdominal
      compression involved pressing with an examining hand over the patient's right
      upper abdomen. RESULTS: Fifty patients were enrolled in the study. The average
      common femoral vein area measured 0.89 cm2 at baseline in the supine position. It
      increased 0.47 cm2 (95% confidence interval [CI] 0.38 to 0.57 cm2) to 1.36 cm2
      with abdominal compression and by 0.90 cm2 (95% CI 0.74 to 1.07 cm2) to 1.79 cm2
      with the Valsalva maneuver. In the reverse Trendelenburg's position, the common
      femoral vein area averaged 1.10 cm2, 0.22 cm2 bigger than the supine baseline
      area (95% CI 0.13 to 0.30 cm2). With additional abdominal compression, the vein
      area increased by 0.71 cm2 to 1.59 cm2 (95% CI 0.59 to 0.83 cm2). With the
      patient performing the Valsalva maneuver in the reverse Trendelenburg's position,
      the vein increased in area 1.07 cm2 (95% CI 0.91 to 1.24 cm2) to 1.96 cm2.
      CONCLUSION: Abdominal compression increases the cross-sectional area of the
      common femoral vein, and the reverse Trendelenburg's position has a further
      additive effect. Abdominal compression may be useful when femoral venous
      cannulation is attempted. In patients who can comply, the Valsalva maneuver may
      be even more effective.

PMID- 18632186
TI  - The relative efficacy of meperidine for the treatment of acute migraine: a meta
      analysis of randomized controlled trials.
AB  - STUDY OBJECTIVE: Despite guidelines recommending against opioids as first-line
      treatment for acute migraine, meperidine is the agent used most commonly in North
      American emergency departments. Clinical trials performed to date have been small
      and have not arrived at consistent conclusions about the efficacy of meperidine.
      We performed a systematic review and meta-analysis to determine the relative
      efficacy and adverse effect profile of opioids compared with nonopioid active
      comparators for the treatment of acute migraine. METHODS: We searched multiple
      sources (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL,
      and LILACS, emergency and headache medicine conference proceedings) for
      randomized controlled trials comparing parenteral opioid and nonopioid active
      comparators for the treatment of acute migraine headache. Our primary outcome was
      relief of headache. If this was unavailable, we accepted rescue medication use or
      we transformed visual analog scale change scores by using an established
      procedure. We grouped studies by comparator: a regimen containing
      dihydroergotamine, antiemetic alone, or ketorolac. For each study, we calculated
      an odds ratio (OR) of headache relief and then assessed clinical and statistical
      heterogeneity for the group of studies. We then pooled the ORs of headache relief
      with a random-effects model. RESULTS: From 899 citations, 19 clinical trials were
      identified, of which 11 were appropriate and had available data. Four trials
      involving 254 patients compared meperidine to dihydroergotamine, 4 trials
      involving 248 patients compared meperidine to an antiemetic, and 3 trials
      involving 123 patients compared meperidine to ketorolac. Meperidine was less
      effective than dihydroergotamine at providing headache relief (OR=0.30; 95%
      confidence interval [CI] 0.09 to 0.97) and trended toward less efficacy than the
      antiemetics (OR=0.46; 95% CI 0.19 to 1.11); however, the efficacy of meperidine
      was similar to that of ketorolac (OR=1.75; 95% CI 0.84 to 3.61). Compared to
      dihydroergotamine, meperidine caused more sedation (OR=3.52; 95% CI 0.87 to
      14.19) and dizziness (OR=8.67; 95% CI 2.66 to 28.23). Compared to the
      antiemetics, meperidine caused less akathisia (OR=0.10; 95% CI 0.02 to 0.57).
      Meperidine and ketorolac use resulted in similar rates of gastrointestinal
      adverse effects (OR=1.27; 95% CI 0.31 to 5.15) and sedation (OR=1.70; 95% CI 0.23
      to 12.72). CONCLUSION: Clinicians should consider alternatives to meperidine when
      treating acute migraine with injectable agents.

PMID- 18632188
TI  - The role of ET(A) and ET(B) receptor antagonists in acute and allergic
      inflammation in mice.
AB  - In this study, we investigated the effects of the selective ET(A) (BQ-123) and
      ET(B) (BQ-788) receptor antagonists for endothelin-1 (ET-1) against several
      flogistic agent-induced paw edema formation and ovalbumin-induced allergic lung
      inflammation in mice. The intraplantar injection of BQ-123, but not BQ-788,
      significantly inhibited carrageenan-, PAF-, ET-1- and bradykinin-induced paw
      edema formation. The obtained inhibitions (1h after the inflammatory stimulus)
      were 79+/-5%, 55+/-4%, 55+/-6% and 74+/-4%, respectively. In carrageenan-induced
      paw edema, the mean ID(50) value for BQ-123 was 0.77 (0.27-2.23)nmol/paw. The
      neutrophil influx induced by carrageenan or PAF was reduced by BQ-123, with
      inhibitions of 55+/-2% and 72+/-4%, respectively. BQ-123 also inhibited the
      indirect macrophage influx induced by carrageenan (55+/-6%). However, BQ-788
      failed to block the cell influx caused by either of these flogistic agents. When
      assessed in the bronchoalveolar lavage fluid in a murine model of asthma, both BQ
      123 and BQ-788 significantly inhibited ovalbumin-induced eosinophil recruitment
      (78+/-6% and 71+/-8%), respectively. Neither neutrophil nor mononuclear cell
      counts were significantly affected by these drugs. Our findings indicate that
      ET(A), but not ET(B), selective ET-1 antagonists are capable of preventing the
      acute inflammatory responses induced by carrageenan, PAF, BK and ET-1. However,
      both ET(A) and ET(B) receptor antagonists were found to be effective in
      inhibiting the allergic response in a murine model of asthma.

PMID- 18632189
TI  - Memory loss caused by beta-amyloid protein is rescued by a beta(3)-adrenoceptor
      agonist.
AB  - Accumulation of the neurotoxic beta-amyloid protein (Abeta) in the brain is a key
      step in the pathogenesis of Alzheimer's disease (AD). Although transgenic mouse
      models of AD have been developed, there is a clear need for a validated animal
      model of Abeta-induced amnesia which can be used for toxicity testing and drug
      development. Intracranial injections of Abeta(1-42) impaired memory in a single
      trial discriminative avoidance learning task in chicks. Memory inhibition was
      closely associated with the state of aggregation of the Abeta peptide, and a
      scrambled-sequence of Abeta(1-42) peptide failed to impair memory. Abeta had
      little effect on labile (short-term and intermediate) memory, but blocked
      consolidation of memory into long-term storage mimicking the type of anterograde
      amnesia that occurs in early AD. Since noradrenaline exerts a modulatory
      influence on labile memory in the chick, we examined the effects of two beta
      adrenoceptor (AR) agonists on Abeta-induced amnesia. A beta(3)-AR agonist
      (CL316243), but not a beta(2)-AR agonist, rescued Abeta-induced memory loss,
      suggesting the need for further studies on the role of beta(3)-ARs in AD.

PMID- 18632190
TI  - Cyclocondensation reaction of heterocyclic carbonyl compounds. Part XIII:
      synthesis and cytotoxic activity of some 3,7-diaryl-5-(3,4,5
      trimethoxyphenyl)pyrazolo[4,3-e][1,2,4]triazines.
AB  - A series of the 3,7-diaryl-5-(3,4,5-trimethoxyphenyl)pyrazolo[4,3
      e][1,2,4]triazines have been synthesized in five steps. The cytotoxic activity of
      all of the newly synthesized compounds has been tested in vitro against five
      cancer cell lines. Several compounds demonstrated significant broad cytotoxic
      activity in low micromolar range, while others were selectively active against
      lung adenocarcinoma cell line A549.

PMID- 18632191
TI  - [A seizure in a patient with systemic lupus erythematosus].

PMID- 18632192
TI  - [Adherence to medication: the challenge of chronic disease].

PMID- 18632193
TI  - Re: Insufficient nutritional knowledge among health care workers?

PMID- 18632194
TI  - Attitudes towards mode of birth among Swedish midwives.
AB  - OBJECTIVE: to investigate midwives' attitudes and opinions on mode of birth.
      DESIGN: exploratory descriptive study. Data were collected via study-specific
      questionnaires during 2006. SETTING: southeastern Sweden. PARTICIPANTS: all
      midwives working in two counties. FINDINGS: regardless of age, experience and
      working field, the midwives considered a reasonable caesarean rate to be around
      11.5 per cent. None of the participants thought that the caesarean rate was too
      low. Midwives younger than 50 years tended to consider the current caesarean rate
      to be too high (p=0.059). Midwives working on labour wards stated that they
      thought the current caesarean rate was too high compared with midwives working at
      antenatal care clinics (ACCs) (p<0.001). Midwives working at ACCs agreed with the
      statements 'one should agree to a woman's right to have an elective caesarean'
      (p<0.001) and 'elective caesarean is the best choice for a woman with fear of
      birth' (p=0.046) more often than midwives working on labour wards, regardless of
      age or working experience. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      midwives working at ACCs are more willing to accept caesarean section at the
      woman's request and for women with fear of birth. It is of importance that ACC
      caregivers and professionals on labour wards increase their collaboration and
      have continuous discussions with one another in an attempt to reach consensus
      about the appropriate caesarean rates on evidence-based grounds.

PMID- 18632195
TI  - Patellofemoral compressive force and stress during the forward and side lunges
      with and without a stride.
AB  - BACKGROUND: Although weight bearing lunge exercises are frequently employed
      during patellofemoral rehabilitation, patellofemoral compressive force and stress
      are currently unknown for these exercises. METHODS: Eighteen subjects used their
      12 repetition maximum weight while performing forward and side lunges with and
      without a stride. EMG, force platform, and kinematic variables were input into a
      biomechanical model, and patellofemoral compressive force and stress were
      calculated as a function of knee angle. FINDINGS: Patellofemoral force and stress
      progressively decreased as knee flexion increased and progressively increased as
      knee flexion decreased. Patellofemoral force and stress were greater in the side
      lunge compared to the forward lunge between 80 degrees and 90 degrees knee
      angles, and greater with a stride compared to without a stride between 10 degrees
      and 50 degrees knee angles. There were no significant interactions between lunge
      variations and stride variations. INTERPRETATION: A more functional knee flexion
      range between 0 degrees and 50 degrees may be appropriate during the early phases
      of patellofemoral rehabilitation due to lower patellofemoral compressive force
      and stress during this range compared to higher knee angles between 60 degrees
      and 90 degrees. Moreover, when the goal is to minimize patellofemoral compressive
      force and stress, it may be prudent to employ forward and side lunges without a
      stride compared to with a stride, especially at lower knee angles between 0
      degrees and 50 degrees. Understanding differences in patellofemoral compressive
      force and stress among lunge variations may help clinicians prescribe safer and
      more effective exercise interventions.

PMID- 18632196
TI  - Do social comparisons explain the association between income inequality and
      health?: Relative deprivation and perceived health among male and female Japanese
      individuals.
AB  - Relative deprivation has been hypothesized as one of the pathways accounting for
      the link between income inequality and health. We tested this hypothesis in a
      large national sample of men and women in Japan. Our survey included a
      probability sample of 22,871 men and 24,243 women aged 25-64, from whom
      information was gathered on demographic variables, household income, occupation
      or employment status, and self-rated health. Our measure of relative deprivation
      was the Yitzhaki Index, which calculates the deprivation suffered by each
      individual as a function of the aggregate income shortfall for each person
      relative to everyone else with higher incomes in that person's reference group.
      We modeled several alternative reference groups, including others with the same
      occupation, others of the same age group, and others living in the same
      geographic area (prefecture), as well as combinations of these. Generalized
      estimating equations demonstrated that higher relative deprivation was associated
      with worse self-rated health. Even after controlling for absolute income as well
      as other sociodemographic factors, the odds ratio and its 95% confidence
      intervals (CI) for poor health ranged from 1.09 (95% CI: 1.02-1.16) to 1.18 (95%
      CI: 1.11-1.26) for men and from 1.10 (95% CI: 1.04-1.16) to 1.16 (95% CI: 1.09
      1.23) for women per 1 million increase in the Yitzhaki Index. As such, relative
      income deprivation is associated with poor self-rated health independently of
      absolute income, and relative deprivation may be a mechanism underlying the link
      between income inequality and population health.

PMID- 18632197
TI  - Explaining gender differences in ill-health in South Korea: the roles of socio
      structural, psychosocial, and behavioral factors.
AB  - This study examines and explains the gender disparity in health despite rapid
      modernization in South Korea where the social structure is still based on
      traditional gender relations. A nationally representative sample of 2897 men and
      3286 women aged 25-64 from the 2001 Korean National Health and Nutrition
      Examination Survey was analyzed. Health indicators included self rated health and
      chronic disease. Age-adjusted prevalence was computed according to a gender and
      odds ratios (OR) derived from logistic regression. Percentage changes in OR by
      inclusion of determinant variables (socio-structural, psychosocial, and
      behavioral) into the base logistic regression model were used to estimate the
      contributions to the gender gap in two morbidity measures. Results showed a
      substantial female excess in ill-health in both measures, revealing an increasing
      disparity in the older age group. Group-specific age-adjusted prevalence of ill
      health showed an inverse relationship to socioeconomic position. When adjusting
      for each determinant, employment status, education, and depression contributed
      the greatest to the gender gap. After adjusting for all suggested determinants,
      78% for self rated health and 86% for chronic disease in excess OR could be
      explained. After stratifying for age, the full model provided a complete
      explanation for the female excess in chronic illness, but for self rated health a
      female excess was still evident for the younger age group. Socio-structural
      factors played a crucial role in accounting for female excess in ill-health. This
      result calls for greater attention to gender-based health inequality stemming
      from socio-structural determinants in South Korea. Cross-cultural validation
      studies are suggested for further discussion of the link between changing gender
      relations and the gender health gap in morbidity in diverse settings.

PMID- 18632198
TI  - Insular activity during passive viewing of aversive stimuli reflects individual
      differences in state negative affect.
AB  - People differ with regard to how they perceive, experience, and express negative
      affect. While trait negative affect reflects a stable, sustained personality
      trait, state negative affect represents a stimulus limited and temporally acute
      emotion. So far, little is known about the neural systems mediating the
      relationship between negative affect and acute emotion processing. To address
      this issue we investigated in a healthy female sample how individual differences
      in state negative affect are reflected in changes in blood oxygen level-dependent
      responses during passive viewing of emotional stimuli. To assess autonomic
      arousal we simultaneously recorded changes in skin conductance level. At the
      psychophysiological level we found increased skin conductance level in response
      to aversive relative to neutral pictures. However, there was no association of
      state negative affect with skin conductance level. At the neural level we found
      that high state negative affect was associated with increased left insular
      activity during passive viewing of aversive stimuli. The insula has been
      implicated in interoceptive processes and in the integration of sensory,
      visceral, and affective information thus contributing to subjective emotional
      experience. Greater recruitment of the insula in response to aversive relative to
      neutral stimuli in subjects with high state negative affect may represent
      increased processing of salient aversive stimuli.

PMID- 18632199
TI  - Stakeholder involvement in agri-environmental policy making--learning from a
      local- and a state-level approach in Germany.
AB  - Recent European regulations for rural development emphasise the requirement to
      involve stakeholder groups and other appropriate bodies in the policy-making
      process. This paper presents two cases involving stakeholder participation in
      agri-environmental development and policy making, targeted at different policy
      making levels. One study was undertaken in Lower Saxony where a local partnership
      developed and tested an agri-environmental prescription, which was later included
      in the state's menu of agri-environmental schemes. In Sachsen-Anhalt, state
      facilitated stakeholder workshops including a mathematical model were used to
      optimise the programme planning and budget allocation at the state level. Both
      studies aimed at improving the acceptance of agri-environmental schemes. The
      authors gauge the effectiveness of the two approaches and discuss what lessons
      can be learned. The experience suggests that the approaches can complement one
      another and could also be applied to rural policy making.

PMID- 18632200
TI  - Editorial comment on: A systematic review and meta-analysis of randomized
      controlled trials with antimuscarinic drugs for overactive bladder.

PMID- 18632201
TI  - A systematic review and meta-analysis of randomized controlled trials with
      antimuscarinic drugs for overactive bladder.
AB  - CONTEXT: Anticholinergic drugs are commonly used in patients with overactive
      bladder (OAB) who do not achieve symptom relief and quality of life improvement
      with conservative management. Several drugs, with different doses, formulations,
      and routes of administration are currently available, making the choice quite
      difficult. OBJECTIVE: To evaluate efficacy and safety of different doses,
      formulations, and route of administration of the available anticholinergic drugs.
      EVIDENCE ACQUISITION: A systematic review of the literature was performed in
      August 2007 using Medline, Embase, and Web of Science. Efficacy (micturitions per
      24h, volume voided per micturition, urgency urinary incontinence episodes per
      24h, incontinence episodes per 24h) and safety (mainly, adverse events and
      withdrawal rates) end points were evaluated in the randomized control trials
      (RCTs) assessing the role of anticholinergic drugs in non-neurogenic OAB. Meta
      analysis of RCTs was conducted using the Review Manager software 4.2 (Cochrane
      Collaboration). EVIDENCE SYNTHESIS: Our systematic search identified 50 RCTs and
      three pooled analyses. Tolterodine immediate release (IR) had a more favorable
      profile of adverse events than oxybutynin IR. Regarding different dosages of IR
      formulations, dose escalation might yield some limited improvements in the
      efficacy but at the cost of significant increase in the rate of adverse events.
      In the comparisons between IR and extended-release (ER) formulations, the latter
      showed some advantages, both in terms of efficacy and safety. With regard to the
      route of administration, use if a transdermal route of administration does not
      provide significant advantage over an oral one. CONCLUSION: Many of the available
      RCTs have good methodological quality. ER formulations should be preferred to the
      IR ones. With regard to IR formulations, dose escalation might yield some
      improvements in the efficacy with significant increase in the AE. More clinical
      studies are needed to indicate which of the drugs should be used as first-,
      second-, or third-line treatment.

PMID- 18632202
TI  - (-)-Epigallocatechin-3-gallate (EGCG) inhibits HGF-induced invasion and
      metastasis in hypopharyngeal carcinoma cells.
AB  - Hepatocyte growth factor (HGF) has recently attracted a considerable amount of
      attention as a stromal-derived mediator in tumor-stromal interactions,
      particularly because of its close involvement in cancer invasion and metastasis,
      and (-)-epigallocatechin-3-gallate (EGCG) can modulate the cell signaling
      associated with angiogenesis, metastasis, and migration of cancer cells. In the
      present study, we have investigated the effects of HGF on invasion and metastasis
      of hypopharyngeal carcinoma cells and the effect of EGCG on blocking HGF-induced
      invasion and metastasis in these cells. We found that HGF promoted the
      autophosphorylation of c-Met, HGF receptor, and that HGF-induced proliferation,
      colony dispersion, migration and invasion of tumors. We also observed that HGF
      enhanced the activity of matrix metalloproteinase (MMP)-9 and urokinase-type
      plasminogen activator (uPA) in hypopharyngeal carcinoma cells. In addition, HGF
      induced the activation of Akt and Erk pathway as a downstreaming pathway of
      invasion. On the other hand, EGCG at physiologically relevant concentration (1
      microM) suppressed HGF-induced tumor motility and MMP-9 and uPA activities, and
      the suppression of Akt and Erk pathway by EGCG was one of the downstream
      mechanisms to facilitate EGCG-induced anti-invasion effects. These results
      suggest that EGCG may serve as a therapeutic agent to inhibit HGF-induced
      invasion in hypopharyngeal carcinoma patients.

PMID- 18632203
TI  - Osteotropic cancers: from primary tumor to bone.
AB  - It has long been recognized that primary cancers spread to distant organs with
      characteristic preference. Bone metastases occur in approximately 70% of patients
      with advanced breast and prostate cancer, causing severe morbidity and
      hospitalization. In the last decade, we have gained a better understanding of the
      mechanisms by which certain tumor types tend to metastasize specifically to bone.
      It appears that the interaction between the organ microenvironment and cancer
      cells is fundamental for establishing metastatic growth. Accordingly, Stephen
      Paget's 'seed and soil' hypothesis - stating that circulating cancer cells (the
      'seeds') disperse in all directions, but can accomplish metastases only in organs
      where the microenvironment (the 'soil') is permissive for their growth - still
      holds forth today. For this reason, this review uses the 'seed and soil'
      hypothesis as a template to discuss novel insight and developments in the bone
      metastasis field.

PMID- 18632204
TI  - Removal of Cr(VI) and As(V) from aqueous solutions by HDTMA-modified zeolite Y.
AB  - The synthesized zeolite NaY from rice husk ash (RHA) and the commercial zeolite
      NaY both modified with surfactants in amounts equal to 50%, 100% and 200% of
      their external cation exchange capacity (ECEC) were used to remove chromate and
      arsenate anions from aqueous solutions. While the unmodified zeolite Y had little
      or no affinity for the Cr(VI) and As(V) anionic species, the surfactant-modified
      zeolite Y (SMZY) showed significant ability to remove of these anions from the
      aqueous solutions. The highest chromates and arsenates adsorption efficiency was
      observed from solutions of pH values 3 and 8, respectively because of the
      dominance of the univalent species of both anions. The adsorption equilibrium
      data were best fitted with the Langmuir isotherm model with the highest removal
      capacities observed for the SMZY initially prepared considering the
      hexadecyltrimethyl ammonium (HDTMA) amount equal to the 100% of the ECEC of
      zeolite Y. Synthesized SMZY remove Cr(VI) and As(V) more than the corresponding
      commercial one due to its lower silica to alumina ratio. Thus, the HDTMA-covered
      modified zeolite Y synthesized using RHA can be used to remove Cr(VI) and As(V)
      from water.

PMID- 18632205
TI  - Removal of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans by
      three coagulants in simulated coagulation processes for drinking water treatment.
AB  - Surface water from Guangzhou to which standard polychlorinated dibenzo-p-dioxins
      (PCDDs) and polychlorinated dibenzofurans (PCDFs) were added was treated by
      coagulation with ferric chloride (FC), polyaluminium chloride (PAC), and
      aluminium sulfate (AS) at optimum removal dosages for nature organic matter (NOM)
      to assess the polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans
      (PCDD/Fs) removal efficiencies. PCDD/Fs in suspended particulate matter (SPM) and
      treated water (TW) after coagulation were analysed. Low residual levels of
      PCDD/Fs were found in treated water after coagulation: 0.8% for FC, 0.9% for PAC,
      and 3.1% for AS. The removal efficiency calculated using these results was >99%
      for FC and PAC and 97-98% for AS. Most PCDD/Fs congeners could be removed by the
      three coagulation processes; the removal efficiency of FC and PAC was similar,
      and slightly higher than that of AS. The results also demonstrate that
      coagulation with FC preferentially removed tetra- and penta-substituted PCDD/Fs
      from raw water.

PMID- 18632206
TI  - Treatment of xylene polluted air using press mud-based biofilter.
AB  - In the present work, biofiltration of xylene vapors has been investigated on a
      laboratory scale biofilter packed with press mud as filter material inoculated
      with activated sludge from pharmaceutical industry. Four various gas flow rates,
      i.e. 0.03, 0.06, 0.09 and 0.12 m(3) h(-1), were tested for inlet xylene
      concentration ranging from 0.2 to 1.2 g m(-3). The biofilter proved to be highly
      efficient in the removal of xylene at a gas flow rate of 0.2m(3) h(-1)
      corresponding to a gas residence time of 2.8 min. For all the tested inlet
      concentrations, the removal efficiency decreased for high gas flow rates. For all
      the tested gas flow rates, a decrease in the removal efficiency was noticed for
      high xylene inlet concentration. The follow-up of carbon dioxide concentration
      profile through the biofilter revealed that the mass ratio of carbon dioxide
      produced to the xylene removed was approximately 2.52, which confirms complete
      degradation of xylene if one considers the fraction of the consumed organic
      carbon used for the microbial growth.

PMID- 18632207
TI  - Potential for phytoextraction of copper, lead, and zinc by rice (Oryza sativa
      L.), soybean (Glycine max [L.] Merr.), and maize (Zea mays L.).
AB  - Phytoextraction by hyperaccumulators has been proposed for decreasing toxic-metal
      concentrations of contaminated soils. However, hyperaccumulators have several
      shortcomings to introduce these species into Asian Monsoon's agricultural fields
      contaminated with low to moderate toxic-metals. To evaluate the phytoextraction
      potential, maize (Gold Dent), soybean (Enrei and Suzuyutaka), and rice
      (Nipponbare and Milyang 23) were pot-grown under aerobic soil conditions for 60d
      on the Andosol or Fluvisol with low to moderate copper (Cu), lead (Pb), and zinc
      (Zn) contamination. After 2 months cultivation, the Gold Dent maize and Milyang
      23 rice shoots took up 20.2-29.5% and 18.5-20.2% of the 0.1molL(-1) HCl
      extractable Cu, 10.0-37.3% and 8.5-34.3% of the DTPA-extractable Cu, and 2.4-6.5%
      and 2.1-5.9% of the total Cu, respectively, in the two soils. Suzuyutaka soybean
      shoot took up 23.0-29.4% of the 0.1molL(-1) HCl-extractable Zn, 35.1-52.6% of the
      DTPA-extractable Zn, and 3.8-5.3% of the total Zn in the two soils. Therefore,
      there is a great potential for Cu phytoextraction by the Gold Dent maize and the
      Milyang 23 rice and for Zn phytoextraction by the Suzuyutaka soybean from paddy
      soils with low to moderate contamination under aerobic soil conditions.

PMID- 18632208
TI  - Chemical activation in view of MSWI bottom ash recycling in cement-based systems.
AB  - In the present study, the feasibility of recycling incinerator bottom ash in
      cementitious systems by means of chemical activation was investigated. Different
      Na-, K- and Ca-based hydroxides and salts were selected for the experiments on
      the basis of their recognized effects on activation of typical pozzolanic
      materials. The evolution of mechanical properties of bottom ash/Portland cement
      mixtures and the leaching of trace metals from the materials were a matter of
      major concern. The experiments were arranged according to a full factorial
      design, which also allowed to derive a predictive model for unconfined
      compressive strength as affected by bottom ash content as well as activator type
      and dosage. Among the activators tested, calcium chloride was found to affect
      mechanical strength far more positively than the other species used, at the same
      time ensuring low metal release from the material. On the other hand, the use of
      potassium sulfate was observed to cause a significant increase in metal leaching
      at pH<12, which was probably associated to the release of contaminants initially
      immobilized within the structure of ettringite as soon as it converted into
      monosulfate over time.

PMID- 18632209
TI  - ZPLD1 gene is disrupted in a patient with balanced translocation that exhibits
      cerebral cavernous malformations.
AB  - The past few years have seen rapid advances in our understanding of the genetics
      and molecular biology of cerebral cavernous malformations (CCM) with the
      identification of the CCM1, CCM2, and CCM3 genes. Recently, we have recruited a
      patient with an X/3 balanced translocation that exhibits CCM. By fluorescent in
      situ hybridization analysis, sequence analysis tools and database mining
      procedures, we refined the critical region to an interval of 200-kb and
      identified the interrupted ZPLD1 gene. We detected that the mRNA expression level
      of ZPLD1 gene is consistently decreased 2.5-fold versus control (P=0.0006) with
      allelic loss of gene expression suggesting that this protein may be part of the
      complex signaling pathway implicated in CCM formation.

PMID- 18632210
TI  - Smoking-related weight control expectancies among African American light smokers
      enrolled in a smoking cessation trial.
AB  - Concern about weight gain following smoking cessation has been frequently
      described in the literature. However, little is known about smoking-related
      weight expectancies among African American, light smokers (defined as < or = 10
      cigarettes per day [CPD] for > 25 of last 30 days). Given the high rate of
      obesity among African Americans, concern about weight gain may be a significant
      barrier to cessation. The association of demographic, psychosocial and tobacco
      related variables and smoking-related weight control expectancies were examined
      in 755 African American regular, light smokers enrolled in a smoking cessation
      trial (number of years smoked=23.9+11.9; CPD=7.6+/-3.2; age=45.1+/-10.7; BMI=31+/
      8.1; 67% female). Overall, participants had minimal smoking-related weight
      control expectancies (M=3.7/10, SD+/-3.4); however, higher weight control
      expectancies were related to female gender, lower dietary fat intake and lower
      internal self-efficacy to refrain from smoking. Further, smoking-related weight
      control expectancies were not associated with cessation outcome at week-26.
      Findings suggest that weight control expectancies exist among some African
      American light smokers and are related to decreased self-efficacy to refrain from
      smoking. However, the relationship between smoking-related weight expectancies
      and health behaviors are complex and modest in magnitude.

PMID- 18632212
TI  - Do midlife hormonal changes play a role in the onset of sporadic Creutzfeldt
      Jakob disease? An epidemiologic perspective.

PMID- 18632211
TI  - Trends in prescription drug abuse and dependence, co-occurrence with other
      substance use disorders, and treatment utilization: results from two national
      surveys.
AB  - OBJECTIVES: This study examined trends in prescription drug abuse and dependence
      (sedatives, tranquilizers, opioids, and stimulants), co-occurrence with other
      substance use disorders and substance abuse treatment utilization among those
      with diagnoses of prescription drug abuse and dependence in two large, nationally
      representative, independent samples of adults in the United States in 1991-1992
      and 2001-2002. METHODS: Two nationally representative cross-sectional samples of
      civilian non-institutionalized adults 18 years or older in the United States, of
      which 52% were women. Data were collected from structured diagnostic interviews
      using the NIAAA Alcohol Use Disorder and Associated Disabilities Interview
      Schedule: Diagnostic and Statistical Manual version IV (DSM-IV). National
      prevalence estimates were derived from the 1991-1992 National Longitudinal
      Alcohol Epidemiologic Survey (n = 42,862) and the 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093). RESULTS: The
      past-year prevalence of prescription sedative abuse, sedative dependence, opioid
      abuse, and opioid dependence increased from 1991-1992 to 2001-2002. The majority
      of individuals with past-year sedative (56.8%), tranquilizer (89.0%), stimulant
      (67.9%) and opioid (74.2%) use disorders also met DSM-IV criteria for an
      additional past-year substance use disorder. The co-occurrence of several forms
      of prescription drug use disorders and other substance use disorders increased
      from 1991-1992 to 2001-2002. A minority of individuals with past-year
      prescription drug abuse and approximately one-half of those with past-year
      prescription drug dependence utilized substance abuse treatment. CONCLUSIONS: The
      findings reinforce the importance of continued national monitoring based on the
      increases in prescription drug abuse and dependence, high co-occurrence with
      other substance use disorders, and underutilization of substance abuse treatment
      services.

PMID- 18632213
TI  - Moderate alcohol consumption may decrease risk of intervertebral disc
      degeneration.
AB  - Intervertebral disc degeneration (IDD) is a serious health problem worldwide.
      Unfortunately, efforts to control IDD are largely unsuccessful. It is therefore
      important to get better understanding of risks. Various evidences indicate that
      moderate alcohol consumption has protective effect on IDD. Here, we review the
      clinical evidence on alcohol consumption and IDD, and propose a possible
      mechanism. There is increasing evidence indicating that moderate alcohol
      consumption keeps the feeding arteries smooth. Furthermore, strong evidence
      indicates that some inflammatory factors are very important in the
      pathophysiology of IDD, while moderate alcohol consumption can decrease the
      expression of these inflammatory factors. Moreover, experimental studies show
      that alcohol exposure could increase the type II collagen and aggrecan, the major
      constituents of nucleus pulposus matrix. Given the above background, we
      hypothesize that moderate alcohol consumption may reduce the risk of IDD.

PMID- 18632214
TI  - Effect of pretreatment anemia on treatment outcome of concurrent
      radiochemotherapy in patients with head and neck cancer.
AB  - PURPOSE: To investigate the effect of anemia on outcome of treatment with
      radiochemotherapy in patients with head-and-neck cancer. METHODS AND MATERIALS:
      The data of 196 patients with Stage II-IV head-and-neck cancer treated with
      concomitant cisplatin-based radiochemotherapy were retrospectively reviewed.
      Anemia was defined according to World Health Organization criteria as hemoglobin
      <130 g/L in men and <120 g/L in women. RESULTS: Fifty-three patients were
      classified as anemic, 143 as nonanemic. The 3-year local control rate of anemic
      and nonanemic patients was 72% and 85%, respectively (p = 0.01). The 3-year
      overall survival rate of anemic and nonanemic patients was 52% and 77%,
      respectively (p = 0.004). In multivariate analysis, anemia was the most
      significant predictor of local control (hazard ratio, 0.37, p = 0.009) and
      survival (hazard ratio, 0.47, p = 0.007). A dose-effect relationship was also
      found for local control (p = .04) and survival (0.04) when grouping by hemoglobin
      concentration: <120, 120-140, and >140 g/L. CONCLUSIONS: Anemia was strongly
      associated with local control and survival in this cohort of patients with head
      and-neck cancer receiving radiochemotherapy.

PMID- 18632215
TI  - Prevention and treatment of functional and structural radiation injury in the rat
      heart by pentoxifylline and alpha-tocopherol.
AB  - PURPOSE: Radiation-induced heart disease (RIHD) is a severe side effect of
      thoracic radiotherapy. This study examined the effects of pentoxifylline (PTX)
      and alpha-tocopherol on cardiac injury in a rat model of RIHD. METHODS AND
      MATERIALS: Male Sprague-Dawley rats received fractionated local heart irradiation
      with a daily dose of 9 Gy for 5 days and were observed for 6 months after
      irradiation. Rats were treated with a combination of PTX, 100 mg/kg/day, and
      alpha-tocopherol (20 IU/kg/day) and received these compounds either from 1 week
      before until 6 months after irradiation or starting 3 months after irradiation, a
      time point at which histopathologic changes become apparent in our model of RIHD.
      RESULTS: Radiation-induced increases in left ventricular diastolic pressure (in
      mm Hg: 35 +/- 6 after sham-irradiation, 82 +/- 11 after irradiation) were
      significantly reduced by PTX and alpha-tocopherol (early treatment: 48 +/- 7;
      late treatment: 53 +/- 6). PTX and alpha-tocopherol significantly reduced
      deposition of collagen types I (radiation only: 3.5 +/- 0.2 mum(2) per 100
      mum(2); early treatment: 2.7 +/- 0.8; late treatment: 2.2 +/- 0.2) and III
      (radiation only: 13.9 +/- 0.8; early treatment: 11.0 +/- 1.2; late treatment:
      10.6 +/- 0.8). On the other hand, radiation-induced alterations in heart/body
      weight ratios, myocardial degeneration, left ventricular mast cell densities, and
      most echocardiographic parameters were not significantly altered by PTX and alpha
      tocopherol. CONCLUSIONS: Treatment with PTX and alpha-tocopherol may have
      beneficial effects on radiation-induced myocardial fibrosis and left ventricular
      function, both when started before irradiation and when started later during the
      process of RIHD.

PMID- 18632216
TI  - Long-term results and prognostic factors of fractionated strontium-90 eye
      applicator for pterygium.
AB  - PURPOSE: To evaluate the long-term safety, effectiveness, and prognostic factors
      of fractionated postoperative beta-irradiation. METHODS AND MATERIALS: Between
      1993 and 2005, 623 patients with 737 pterygium lesions were treated with a
      strontium-90 eye applicator after surgical excision. The median follow-up period
      was 60 months (range, 6.7-139.5). Of the 737 lesions, 644 were primary and 93
      were recurrences after surgical removal alone. Fractionated radiotherapy (RT) to
      a total dose of 35 Gy in five to seven fractions was used. RESULTS: A total of 73
      local pterygium recurrences (9.9%) were noted. Of the recurrent cases, 80% were
      noted within 3 years after treatment. The 5- and 10-year probability of local
      control was 90% and 88%, respectively. The multivariate analysis for all cases
      demonstrated that gender, age, total radiation dose, recurrent pterygia, and
      interval between surgery and RT affected the overall local control rate. Late
      toxicities that might have been associated with strontium-90 RT included
      scleromalacia (scleral thinning) in nine eyes, adhesion of the eyelids in eight,
      cataracts in six, and scleral ulcer in five eyes. CONCLUSION: Fractionated
      strontium-90 RT to a total dose of approximately 35 Gy in five to seven fractions
      results in a similar local control rate as higher doses in other series, with an
      acceptable complication rate.

PMID- 18632217
TI  - FDG-PET-based radiotherapy planning in lung cancer: optimum breathing protocol
      and patient positioning--an intraindividual comparison.
AB  - PURPOSE: Fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET) and
      PET/computed tomography (CT) are increasingly used for radiotherapy (RT) planning
      in patients with non-small-cell lung carcinoma. The planning process often is
      based on separately acquired FDG-PET/CT and planning CT scans. We compared
      intraindividual differences between PET acquired in diagnostic (D-PET) and RT
      treatment position (RT-PET) coregistered with planning CTs acquired using
      different breathing protocols. METHODS AND MATERIALS: Sixteen patients with non
      small-cell lung carcinoma underwent two PET acquisitions (D-PET and RT-PET) and
      three planning CT acquisitions (expiration [EXP], inspiration [INS], and mid
      breath hold [MID]) on the same day. All scans were rigidly coregistered,
      resulting in six fused data sets: D-INS, D-EXP, D-MID, RT-INS, RT-EXP, and RT
      MID. Fusion accuracy was assessed by three readers at eight anatomic landmarks,
      lung apices, aortic arch, heart, spine, sternum, carina, diaphragm, and tumor, by
      using an alignment score ranging from 1 (no alignment) to 5 (exact alignment).
      RESULTS: The RT-PET showed better alignment with any CT than D-PET (p < 0.001).
      With regard to breathing, RT-MID showed the best mean alignment score (3.7 +/-
      1.0), followed by RT-EXP (3.5 +/- 0.9) and RT-INS (3.0 +/- 0.8), with all
      differences significant (p < 0.001). Comparing alignment scores with regard to
      anatomic landmarks, the largest deviations were found at the diaphragm, heart,
      and apices. Overall, there was fair agreement (kappa = 0.48; p < 0.001) among the
      three readers. CONCLUSIONS: Significantly better fusion of PET and planning CT
      can be reached with PET acquired in the RT position. The best intraindividual
      fusion results are obtained with the planning CT performed during mid-breath
      hold. Our data justify the acquisition of a separate planning PET in RT treatment
      position if only a diagnostic PET scan is available.

PMID- 18632218
TI  - Which socio-demographic factors are associated with participation in oral cancer
      screening in the developing world? Results from a population-based screening
      project in India.
AB  - BACKGROUND: This study examines socio-demographic determinants of participation
      in a population-based randomized controlled trial that proved that oral visual
      inspection was effective in reducing oral cancer mortality in high-risk
      individuals in India. METHODS: Multivariate logistic regression was used to
      establish socio-demographic characteristics of participants versus non
      participants in the intervention arm. Compliance with referral was analysed
      according to the socio-demographic characteristics of screen-positives. RESULTS:
      Of 96,517 eligible subjects, 87,655 were screened, 8688 individuals never
      received the invitation and 174 refused screening. Compared to the non-screened,
      a higher proportion of screened individuals were women (OR=4.51; CI: 4.28-4.75),
      lived in better housing (OR=1.35; CI: 1.25-1.41), had television/radio (OR=1.50;
      CI: 1.43-1.58) and were tobacco and alcohol users (OR=2.75; CI: 2.57-2.95). Being
      65 and older decreased the chances of screening (OR=0.39; CI: 0.37-0.42), as well
      as living in high-size households (OR=0.73; CI: 0.68-0.78). Sixty-three percent
      of 5143 screen-positives complied with referral. Controlling for all other
      factors, individuals older than 44, and those with more advanced lesions were
      more likely to comply with referral (p<0.001). Individuals living in better
      housing were less likely to comply with referral (OR=0.79; CI: 0.65-0.95).
      CONCLUSIONS: In summary, adequate coverage can be obtained in population-based
      oral screening in developing countries. The study underscores the important role
      of patient-provider communication in assuring high compliance with referral.

PMID- 18632219
TI  - The prevalence of signs and symptoms of childhood leukemia and lymphoma in Fars
      Province, Southern Iran.
AB  - BACKGROUND: Leukemia and lymphomas are still the common childhood cancers in
      Iran. This study was undertaken to determine the prevalence of signs and symptoms
      of these malignancies in children of Fars Province, Southern Iran. METHODS: A
      total of 368 cases of children who were less than 15 years old and diagnosed as
      acute lymphocytic leukemia (ALL, n=211), acute myeloid leukemia (AML, n=64),
      Burkitt lymphoma (BL, n=40), chronic myeloid leukemia (CML, n=5), Hodgkin's
      disease (HD, n=33) or non-Burkitt-type, non-Hodgkin's lymphoma (NBNHL, n=15)
      referring to the hospitals of Shiraz University of Medical Sciences from April
      1997 to March 2002 were enrolled. A questionnaire was provided to record the age,
      median age at the onset of the disease, sex, type of malignancy and the signs and
      symptoms at the time of presentation. RESULTS: The common sign or symptoms were
      fever (74%), in ALL, AML, NHL, and BL patients, hepatosplenomegaly (100%) in CML
      patients, and lymphadenopathy (54%) and fever (54%) in Hodgkin's disease.
      CONCLUSION: Knowledge of signs and symptoms and types of presentations of
      childhood leukemia and lymphoma may help a physician to improve the patient's
      outcome. This study revealed that attention to uncommon signs and symptoms in
      history taking and physical examination together with laboratory tests may
      increase the physicians' awareness and better diagnosis of pediatric malignancies
      and would also be beneficial for the patient.

PMID- 18632221
TI  - Hypermethylation of epithelial-cadherin gene promoter is associated with Epstein
      Barr virus in nasopharyngeal carcinoma.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is documented as the important etiologic
      agent of nasopharyngeal carcinoma (NPC) but the mechanism of development and
      pathogenesis induced by EBV is presently unclear. Hypermethylation of epithelial
      cadherin (E-cadherin) promoter has been shown to be induced in NPC cell line by
      EBV LMP1 via DNA methyltransferase activation. EBV genomes and hypermethylation
      of E-cadherin promoter were investigated in NPC tissues to evaluate the role of
      EBV in the hypermethylation and pathogenesis of NPC. METHODS: Methylation
      specific polymerase chain reaction (MSP) was performed to detect E-cadherin
      promoter hypermethylation in paraffin embedded tissues from patients with NPC and
      normal nasopharyngeal tissues. EBV genomes were detected by PCR in the tissue
      samples. RESULTS: Hypermethylation of E-cadherin promoter and EBV were
      predominantly detected in undifferentiated and non-keratinizing NPC compared to
      those in squamous cell NPC. Hypermethylation of E-cadherin was found in 28 of 38
      (73.7%) patient samples. EBV was detected in 22 of the 28 (78.6%) NPC samples
      demonstrating E-cadherin hypermethylation. EBV genomes and hypermethylation were
      not detected in normal nasopharyngeal tissues. Significant association was found
      between E-cadherin hypermethylation and EBV genomes (p<0.001; Fisher's exact
      test). Hypermethylation of E-cadherin was more frequently detected in advanced
      stages compared to those in early stages of NPC (p=0.036; Fisher's exact test).
      CONCLUSIONS: The high incidence of EBV with the consistency of E-cadherin
      hypermethylation, particularly in undifferentiated and non-keratinizing NPC
      suggests the role of EBV in the hypermethylation. EBV exists at early stage of
      NPC that induces the hypermethylation and contributes to progression of the
      disease to the advanced stage of NPC.

PMID- 18632220
TI  - COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and
      stromal tissue compartments in a spectrum of esophageal squamous neoplasia.
AB  - BACKGROUND: Previous studies have shown important effects of stromal elements in
      carcinogenesis. To explore the tumor-stromal relationship in esophageal
      neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically
      associated with the development of gastrointestinal cancers, in adjacent foci of
      epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in
      sections of normal squamous epithelium, squamous dysplasia and invasive
      esophageal squamous cell carcinoma. METHODS: Adjacent foci of epithelium,
      subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were
      laser microdissected from six fully embedded, ethanol fixed, esophagectomy
      samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter
      CpG site-specific hypermethylation status of COX-2 was determined using real-time
      methylation-specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation
      status of a subset of samples was confirmed by pyrosequencing. RESULTS: Forty
      nine microdissected foci were analyzed. COX-2 gene methylation was significantly
      more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in
      epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17
      (18%)) (Fisher's exact p=0.05). Two of three epithelial samples and all three
      stromal samples that showed COX-2 methylation were adjacent to foci of methylated
      subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a
      subset of samples. CONCLUSIONS: In these esophageal cancer patients, COX-2 gene
      methylation was more common in subepithelial lymphocytes than in adjacent
      epithelial or stromal cells in both grades of dysplasia and in foci of invasive
      cancer. These findings raise the possibility that methylation of subepithelial
      lymphocytes may be important for tumorigenesis. Future studies of gene
      methylation should consider separate evaluation of epithelial and non-epithelial
      cell populations.

PMID- 18632222
TI  - Loss of heterozygosity in the RAD51 and BRCA2 regions in breast cancer.
AB  - BACKGROUND: Loss of heterozygosity (LOH) in the 15q14-21 and 13q12-13 regions can
      contribute to the inactivation of RAD51 and BRCA2 genes implicated in the
      pathogenesis of breast cancer. We investigated allelic losses in microsatellites
      in the RAD51 and BRCA2 regions, and their association with clinicopathological
      parameters in breast cancer. METHODS: The LOH analysis was performed by
      amplifying DNA by PCR, using D15S118, D15S214, D15S1006 polymorphic markers in
      the 15q14-21 region and D13S260, D13S290 polymorphic markers in the 13q12-13
      region in 36 sporadic breast cancer cases. RESULTS: LOH in the RAD51 region
      ranged from 29% to 46% and in the BRCA2 region from 38% to 43% of informative
      cases. Eleven percent of the breast cancer cases displayed LOH for at least one
      studied marker in the RAD51 region exclusively. On the other hand, 44% of cases
      manifested statistically significant LOH for at least one microsatellite marker
      concomitantly in the RAD51 and BRCA2 regions. LOH in the RAD51 region similarly
      as in the BRCA2 region appeared to correlate with steroid receptors content and
      lymph node status. DISCUSSION: The obtained results indicate that alteration in
      RAD51 region may contribute to the disturbances of DNA repair involving RAD51
      and/or BRCA2 penetration and thus enhance the risk of breast cancer development.

PMID- 18632223
TI  - Evidence for a programming effect of early menarche on the rise of breast cancer
      incidence in Hong Kong.
AB  - BACKGROUND: Younger age at menarche and older age at first live birth are
      implicated as risk factors for breast cancer, but the extent to which these
      factors contribute to the sharply rising incidence of this disease in developing
      countries has received little study. METHODS: We conducted a retrospective
      analysis of 702 consecutive breast cancer patients diagnosed at a single hospital
      in Hong Kong during 2003-2006. Comparisons were made between patients with
      different ages at cancer diagnosis (hence, belonging to different birth cohorts)
      and their respective ages at menarche and at first live birth. We then correlated
      these age-dependent differences with overall breast cancer incidence data from
      the Hong Kong Cancer Registry. RESULTS: When patients diagnosed before age 40 are
      compared with those after 60, the age of menarche is lower in the former subgroup
      (12.7 vs. 14.2; p<10(-6)) while the age of first live birth is greater (28.2 vs.
      25.5; p<0.01). However, registry data suggest that the progressive rise in breast
      cancer incidence has not affected those over 65, nor very young (20-39 years)
      patients. CONCLUSION: Lifestyle variables that reduce age at menarche may
      contribute to the rising risk of breast cancer diagnosed after age 40 in Hong
      Kong, whereas earlier-onset cancers may be characterised by a distinct
      pathogenesis. Although retrospective, these data raise the possibility that
      cancer-preventive health interventions could gainfully target reversible risk
      factors favoring early menarche - such as formula infant feeding, high-fat diets,
      and lack of exercise - in children and adolescents living in developing countries
      such as China.

PMID- 18632224
TI  - Companion's effects upon resistance to change.
AB  - In order to investigate the effects of a companion's presence on resistance to
      change, five rats were trained under a multiple schedule comprised of components
      with high versus low rate of water reinforcement. After response rates became
      stable, water was given to the subjects prior to the experimental sessions, and
      these were conducted both in the absence and in the presence of a companion,
      which also could be responding or merely present. Results showed that the
      companion's presence increased resistance to satiation, mainly during the
      component with the higher reinforcement rate. These results suggest that the
      effect of the companion's presence may interact with reinforcement rate in
      determining response rate and resistance to satiation.

PMID- 18632225
TI  - Lower GC-content in editing exons: implications for regulation by molecular
      characteristics maintained by selection.
AB  - We unexpectedly discover that there are much lower GC3 and GC-content and higher
      Gibbs free energy on editing exons than other exons in the Drosophila
      synaptotagmin I transcripts, which was further, confirmed statistically by others
      47 experimentally-validated samples. Sequence alignment, Ks and Ka/Ks assays
      suggest that rapidly ascending purifying selection occur in editing exons which
      constrains nucleotide divergency. The presence of specific molecular
      characteristics such as lower GC-content in editing exons imply an unexpected
      requirement and are likely to direct RNA editing occurrence. Thus, relations
      between molecular characteristics of DNA, RNA editing and purifying selection
      might be present.

PMID- 18632226
TI  - Vaccine failure caused an outbreak of equine influenza in Croatia.
AB  - In April 2004 an outbreak of equine influenza occurred at the Zagreb hippodrome,
      Croatia. Clinical respiratory disease of the same intensity was recorded in
      vaccinated and non-vaccinated horses. The equine influenza vaccine used in
      Croatia at the time of the outbreak contained the strains A/equine/Miami/63
      (H3N8), A/equine/Fontainebleau/79 (H3N8) and A/equine/Prague/56 (H7N7). At the
      same time, the usual strains in vaccines used in Europe were, in accordance with
      the recommendation of the World Organisation for Animal Health (OIE) Expert
      Surveillance Panel on equine influenza, A/equine/Newmarket/1/93 (H3N8) and
      A/equine/Newmarket/2/93 (H3N8). At the same time, some current vaccines in the
      USA contained A/equine/Kentucky/97 (H3N8). Genetic characterization of the HA1
      portion of the haemagglutinin (HA) gene of virus isolated from the outbreak
      indicated that the isolate (A/equine/Zagreb/04) was an H3N8 strain closely
      related to recent representative viruses of the American lineage Florida sub
      lineage. In comparison with both H3N8 vaccine strains used in horses at the
      Zagreb hippodrome, A/equine/Zagreb/04 displayed amino acids changes localised to
      4 of the 5 described antigenic sites (A-D) of subunit protein HA1. Comparison of
      the amino acid sequence of the HA1 subunit protein of the outbreak strain with
      that of A/equine/Newmarket/1/93 displayed three amino acids changes localised in
      antigenic sites B and C, while antigenic sites A, D and E were unchanged. The
      Zagreb 2004 outbreak strain had the same amino acids at antigenic sites of the
      HA1 subunit protein as the strain A/equine/Kentucky/97. Amino acid changes in
      antigenic sites between HA1 subunit of the outbreak strain and the strains used
      in the vaccines likely accounted for the vaccine failure and the same clinical
      signs in vaccinated and unvaccinated horses. Use of a recent strain in vaccines
      should limit future outbreaks.

PMID- 18632227
TI  - Isolation of Mycobacterium bovis and other mycobacterial species from ferrets and
      stoats.
AB  - As part of wildlife surveillance for bovine tuberculosis, pooled lymph nodes from
      21,481 ferrets, 1056 stoats and 83 weasels were cultured for mycobacteria. A
      total of 268 isolates of Mycobacterium bovis were obtained from ferrets, 2 from
      stoats and none from weasels, demonstrating the presence of a wildlife reservoir
      of infection in ferrets. DNA typing by restriction endonuclease analysis (REA) of
      48 selected isolates of M. bovis revealed 23 REA types. Twenty-one of these types
      had previously been isolated from cattle and farmed deer, demonstrating a complex
      cycle of infection involving wildlife and domestic animals. Apart from M. bovis,
      a further 208 mycobacterial isolates were obtained, the majority of which (178)
      were members of the M. avium complex. Speciation of the remaining 30
      mycobacterial isolates by DNA sequencing of the 16s rRNA gene, identified half
      the isolates as M. triplex. Other species identified included M. fortuitum, M.
      florentinum, M. interjectum, M. intracellulare, M. holsaticum, and M. septicum/M.
      peregrinum.

PMID- 18632228
TI  - Characterization of ISApl1, an insertion element identified from Actinobacillus
      pleuropneumoniae field isolate in China.
AB  - An insertion sequence (IS), designated ISApl1, was identified in Actinobacillus
      pleuropneumoniae. It was 1072 bp in length, and contained a large open reading
      frame (ORF), which encoded a putative transposase whose sequence was similar to
      that of transposases of various IS elements of the IS30 family. Another small
      ORF, a putative antisense repressor of transposase, was located in the opposite
      direction of transposase. ISApl1 generated a 3-bp duplication of the target DNA
      and carried 24-bp inverted repeats sequence. ISApl1 was identified in the genome
      of a biofilm-formation negative A. pleuropneumoniae strain field isolate HB04 and
      inserted into an A/T rich region of the ORF of pgaC, which encoded the PGA [N
      acetyl-D-glucosamine residues in beta(1,6) linkage] synthesizing N
      glycosyltransferase. The genotype of the pgaC(-)/IS(+) was not altered after re
      isolation from challenged mice, which indicated that this IS element was
      relatively stable in A. pleuropneumoniae during infection.

PMID- 18632229
TI  - Persistent maternal anxiety affects the interaction between mothers and their
      very low birthweight children at 24 months.
AB  - BACKGROUND: Parental distress following the birth of a premature infant
      diminishes the parent's ability to be sensitive to the infant's cues, and this
      may affect infant developmental outcomes. AIMS: The present study examined the
      effects of maternal anxiety during infant hospitalization in the Neonatal
      Intensive Care Unit (NICU) on the interactive behavior of mothers with their very
      low birthweight (VLBW) children in toddlerhood. SUBJECTS: A sample of 56 mothers
      and their VLBW infants were recruited in the NICU. STUDY DESIGN: During the
      infant's NICU stay, mothers completed a self-report measure of trait anxiety.
      These mothers and their infants were followed when the infants were 24 months
      corrected age, when mothers and their children were videotaped during free play
      at home. These videotapes were then coded using the Emotional Availability
      Scales. RESULTS: Maternal anxiety was not found to be related to severity of
      neonatal illness. Maternal anxiety in the NICU was associated with less
      sensitivity and less structure in interaction with their toddlers at 24 months
      corrected age, even controlling for maternal education and child birthweight.
      Children of mothers with higher anxiety scores in the NICU were less likely to
      involve their mothers in their play at 24 months corrected age. CONCLUSIONS:
      Maternal anxiety in the NICU predicted adverse interactive behaviors when the
      children were 24 months corrected age. Early identification of anxious mothers in
      the NICU is needed in order to initiate preventive intervention to support the
      mother-infant relationship.

PMID- 18632230
TI  - Seminal traits, suitability for semen preservation and fertility in the native
      Portuguese horse breeds Puro Sangue Lusitano and Sorraia: Implications for
      stallion classification and assisted reproduction.
AB  - The Puro Sangue Lusitano (PSL) is the major national breed of horse in Portugal,
      but no studies exist on its seminal characteristics, or on the possibility of
      conserving semen for future use. The aim of this study was to evaluate semen
      parameters, fertility and the aptness to semen preservation in Lusitano
      Stallions. In order to compare characteristics defined by a single or by multiple
      semen collections per stallion 152 ejaculates obtained from 152 Lusitano
      stallions presented at an annual breeding soundness examination as well as data
      related to 371 ejaculates obtained from 9 PSL were analyzed. These latter samples
      were also evaluated in terms of their possible use in assisted reproduction and
      were compared with 113 ejaculates obtained from 4 Sorraia horses, a rare and
      endangered Portuguese breed. The percentage of motile spermatozoa (PMS) was
      assessed after collection (AC), after semen dilution (AD) and at 24h of cool
      storage. Mean values obtained for sperm motility and morphology and semen pH
      observed after semen collection differ significantly (P<0.05) between single
      collection/multiple stallions and multiple collections/limited stallions, and no
      age related effects were detected. Overall, Lusitano semen quality was comparable
      to that of related breeds, while Sorraia stallions had very poor semen quality.
      The response to cool-storage of diluted semen samples differed among stallions
      and breeds, and the best results for progressive motile sperm cells at 24h were
      in a range of 35-53% for PSL stallions and were lower for Sorraia stallions.
      Fertility rates obtained with artificial insemination (AI) averaged at 85% for
      PSL. With the exception of PMS AC, sperm vitality and semen pH no other seminal
      trait seemed to influence fertility rates in the Lusitano breed.

PMID- 18632231
TI  - Investigation of isotopic linkage between precursor and product in the synthesis
      of a high explosive.
AB  - In criminal proceedings involving illegally manufactured substances, evidence
      demonstrating the manufacture is required for successful prosecution. In many
      circumstances the presence of manufacturing equipment and 'recipes' are clear
      indicators. However establishing chemical links between starting materials and
      products would be beneficial additional evidence in such circumstances. Isotope
      analysis is becoming more commonly employed in disputes over authenticity and
      provenance of materials such as food stuffs or pharmaceuticals [S. Benson, C.
      Lennard, P. Maynard, C. Roux, Forensic applications of isotope ratio mass
      spectrometry--a review, Forensic Sci. Int., 157 (2006) 1-22]. We report here the
      results of an isotope study investigating a link between hexamine used as a
      starting material and the product explosive RDX, manufactured using the Woolwich
      process. Isotopic composition of hexamine and RDX was analysed by stable isotope
      ratio mass spectrometry. Five different hexamine samples were selected from a
      group of eleven for use in this study. One of the five hexamine samples was used
      twice, providing data on the reproducibility of the synthesis. Carbon and
      nitrogen isotope analysis of the hexamine starting material and RDX products
      reveals a reproducible relationship between reactant and product.

PMID- 18632232
TI  - Experimental evaluation of the impact of seating depth variations on observed
      marks on primers.
AB  - Although the examination of bullet and primer striae patterns is still a very
      important task in forensic ballistics, a fundamental explanation or theoretical
      model for reasoning about the (ir)reproducibility of the observed marks is still
      non-existing. More specifically, it is still unclear which ammunition production
      or firing condition parameters may play an important role in the striae and marks
      formation process. From a practical point of view this situation is unfortunate
      because a proper knowledge of these parameters and conditions could help underpin
      and explain certain differences found in actual casework investigations.
      Additionally, a proper understanding of these issues could allow examiners to
      select or develop a near-optimal test firing procedure by using more detailed and
      controlled variations of certain intra- and/or inter-ammunition parameters than
      the ones that are in use today. In this paper, we discuss the results of an
      experiment aimed at evaluating the impact of primer seating depth variations on
      observed primer striae and other marks. First, three sets of cartridge cases with
      different seating depth intervals were selected. Second, each of these sets were
      fired consecutively using a selected pistol. Finally, the cartridge cases were
      examined using both traditional optical microscopes and three-dimensional (3D)
      profilometer techniques. The results reported in this paper show that in our
      experiments no important impact of the initial primer seating depth on the
      observed primer striae patterns could be found, but that the firing pin
      impression does seem to change if the initial seating depth is larger than a
      certain threshold.

PMID- 18632233
TI  - Treatment results and prognostic factors for advanced squamous cell carcinoma of
      the head and neck treated with concurrent chemoradiotherapy.
AB  - OBJECTIVE: To review our experience in the treatment of concurrent
      chemoradiotherapy (CCR) for patients with advanced squamous cell carcinoma of the
      head and neck (SCCHN) and to evaluate the different factors affecting survival
      and primary organ preservation. METHODS: We reviewed the records of 101 patients
      with SCCHN treated with CCR between February 1998 and April 2004. Of 101
      patients, 76 were treated with a cisplatin, 5-fluorouracil, methotrexate, and
      leucovorin (PFML) regimen and 25 were treated with a carboplatin and uracil
      tegafur (CBDCA-UFT) regimen. Overall survival (OS), disease-specific survival
      (DSS) and DSS with primary organ preservation were estimated using Kaplan-Meier
      methods. The log-rank test and Cox proportional hazards regression were employed
      to identify significant prognostic factors for OS, DSS, and DSS with primary
      organ preservation. RESULTS: The 5-year OS and DSS for all patients were 51.6 and
      67.4%, respectively. On multivariate analysis, resectability of the tumor and
      degree of histological differentiation were significant predictors of survival
      for patients undergoing CCR; T stage and differentiation were significant
      prognostic factors for primary organ preservation. CONCLUSION: In the treatment
      of CCR for advanced SCCHN, the survival rate of the patients with resectable
      tumors was excellent and significantly greater compared with the patients with
      unresectable tumors. T1 to T3 disease in patients with advanced resectable SCCHN
      is a good predictor of organ preservation. CCR may improve not only primary organ
      preservation (local control) but also survival in patients with poorly
      differentiated tumors.

PMID- 18632234
TI  - Novel de novo splice-site mutation of SCN1A in a patient with partial epilepsy
      with febrile seizures plus.
AB  - This report describes a 4-year-old male patient experienced prolonged febrile
      seizures after 1 year of age, multiple febrile seizures and complex partial
      seizures with secondary generalization. The gene encoding voltage-gated sodium
      channel alpha1-subunit: SCN1A analysis revealed a heterozygous de novo one-point
      mutation (IVS16+2 T>C) at a splice-acceptor site. This mutation was inferred to
      cause truncation of the alpha1-subunit molecule and, thereby, a loss of channel
      function. To date, truncation mutation has been found exclusively in patients
      with severe myoclonic epilepsy in infancy (SMEI), although only missense
      mutations have been found in generalized epilepsy with febrile seizures plus
      (GEFS+), partial epilepsy with FS+, FS+, and FS. The patient's phenotype is
      consistent with that of partial epilepsy with FS+, rather than SMEI, including
      borderline SMEI (SMEB). We present the first case report of partial epilepsy with
      FS+ associated with a truncation mutation of SCN1A. The possibility exists for
      concomitant involvement of multiple genes other than SCN1A for seizure
      phenotypes.

PMID- 18632235
TI  - HydroCoil occlusion for treatment of traumatic carotid-cavernous fistula:
      preliminary experience.
AB  - OBJECTIVE: To summarize our preliminary experiences regarding HydroCoil occlusion
      for the treatment of carotid-cavernous fistula (CCF), and to evaluate the
      effectiveness of this treatment. METHODS: From January 2006 to June 2007, 15
      patients with traumatic CCF who were treated using HydroCoil occlusion were
      included in this study. All the patients presented with symptoms such as
      intracranial pulsatile noise, bulbar conjunctival hyperemia, and pulsatile
      exophthalmia. Cerebral angiography revealed that the fistula was located in the
      right internal carotid-cavernous segment in 6 cases, in the left internal carotid
      cavernous segment in 8 cases, and on both sides in 1 case. RESULTS: After CCF
      procedure, in 15 patients, the fistula was no longer visualized, the internal
      carotid artery on the affected side remained patent, and intracranial noise
      disappeared immediately. The preoperative symptoms exophthalmia, bulbar
      conjunctival hyperemia, etc., returned to normal 1 week after the operation.
      Vision recovered to varying extents. In the 9 patients who underwent 1-3 months
      of follow-up cerebral angiography, CCF recurrences and neurological complications
      were not observed. CONCLUSION: Intravascular occlusion has been widely used for
      CCF treatment, and detachable balloon embolization remains the preferred
      treatment. In the case of failure of detachable balloon embolization because the
      patient cannot tolerate the procedure or internal carotid artery occlusion on the
      affected side is contraindicated, HydroCoil occlusion is a safe and effective
      though expensive alternative and a stable method of maintaining high carotid
      artery patency.

PMID- 18632236
TI  - Transarterial ethanol ablation for sporadic and non-hemorrhaging angiomyolipoma
      in the kidney.
AB  - PURPOSE: We evaluated the efficacy and side effects of transarterial ethanol
      ablation in sporadic and non-hemorrhaging angiomyolipomas (AMLs) in the kidney.
      MATERIAL AND METHODS: A total of 10 patients with solitary and sporadic AMLs
      underwent selective transarterial absolute ethanol ablation for prophylaxis
      against hemorrhage. We confirmed the ratio areas of tumor vessel on angiogram,
      those of infraction on post-ablation computed tomography (CT) and those of tumor
      reduction in a 3-, 6- and 12-month follow-up CT. RESULTS: Once or twice a single
      infusion of 1 or 2 ml absolute ethanol achieved in a total occlusion of 22
      feeding arteries which consisted of 7 proximal interlobar arteries, 12 distal
      interlobar arteries and 3 renal capsular arteries. Nontarget occlusion did not
      occur by ethanol reflux in any cases but occurred causing spasms provoked by
      repeated inflation and deflation of the balloon in one case. Total occlusion of
      tumor vessels was observed in 7 patients and 92-95% occlusion in 3. Ethanol
      ablation produced 1.8-22.5% (mean 8.4+/-6.8%) areas of infarctions but the
      outcome was not serious in all cases. Mean percentage areas of tumor reduction
      were 29.4+/-10.6% in a 3-month follow-up, 45.7+/-11.9% in a 6-month and 59.3+/
      11.5% in a 12-month follow-up. CONCLUSIONS: Absolute ethanol ablation for
      sporadic and non-hemorrhaging AML is safe and effective in reducing majority of
      tumor area in a 1-year follow-up.

PMID- 18632237
TI  - Functional residual capacity breath hold for subtraction image of dynamic liver
      MRI.
AB  - PURPOSE: In dynamic liver magnetic resonance imaging (MRI) studies, there are
      problems with misregistration when subtraction images are processed. For
      reduction of the misregistration, a functional residual capacity (FRC) phase
      breath-hold (FRC B-H) method was used. MATERIAL AND METHODS: Sixty patients (32
      males and 28 females, aged 33-85 years, median age 69 years) were examined. The
      subjects were chronologically categorized into two groups: a voluntary expiratory
      (VE) B-H group and a FRC B-H group. The blood-flow phase images were classified
      as plain, arterial, portal and parenchymal phases. To evaluate the
      reproducibility of liver positions between VE B-H and FRC B-H in each phase
      (between Plain and Arterial, Arterial and Portal, Plain and Parenchymal), the
      misregistration areas were compared on the top of the liver. RESULTS: The
      misregistration area between Plain-Arterial, Arterial-Portal and Plain
      Parenchymal in VE B-H was 731.0+/-1153.6, 1134.9+/-1357.2 and 628.4+/-844.5
      (cm(2)), respectively. The misregistration area between each phase in FRC B-H was
      386.4+/-874.9, 574.5+/-1086.1 and 279.8+/-551.2 (cm(2)), respectively. Using the
      Mann-Whitney U-test as quantitative analysis, the difference in misregistration
      areas between two groups was statistically significant (p<0.05). Differences in
      the qualitative analysis were also significant according to the chi(2) test
      (p<0.05). CONCLUSION: The liver positions with FRC B-H were markedly more
      reproducible than those with VE B-H. To improve the registration accuracy of
      subtraction dynamic liver MRI, the FRC B-H should be used.

PMID- 18632238
TI  - Volumes and growth rates of untreated adult low-grade gliomas indicate risk of
      early malignant transformation.
AB  - Adult low-grade gliomas (LGG) grow slowly, but most eventually undergo malignant
      transformation. The relationship between tumour volume, growth rate and the
      likelihood of transformation is unknown. Twenty-seven patients with biopsy
      proven, untreated LGG had at least three MRI studies at 6 monthly intervals.
      Tumour volumes and growth rates were calculated using semi-automated
      segmentation, and analysed in a hierarchical regression model. In a 3-year
      period, patients who showed clinical deterioration and/or new (or significantly
      increased) contrast enhancement were classified as transformers (T), whilst non
      transformers (NT) remained stable clinically and by conventional radiological
      criteria. All LGG showed progressive growth. Volumes at study entry were smaller
      in 9NT (57 ml, 95% CI 35-80 ml) than in 18T (83 ml, 95% CI 70-96 ml) (p=0.03).
      Average annual growth rates were lower in NT (16% (95% CI 9-23%)) than in T (26%
      (95% CI 20-31%)) (p=0.046), until the penultimate study. Growth in T increased to
      56% p.a. (95% CI 20-92%) in the 6 months prior to transformation. In T, tumour
      volume was the most significant predictor of transformation in the following 12
      months. Sequential measurement of LGG volume allows accurate determination of
      growth rates and identification of patients whose tumours are at high risk of
      early transformation.

PMID- 18632239
TI  - Rapid and reliable quantification of reovirus type 3 by high performance liquid
      chromatography during manufacturing of Reolysin.
AB  - Reolysin, a human reovirus type 3, is being evaluated in the clinic as an
      oncolytic therapy for various types of cancer. To facilitate the optimization and
      scale-up of the current process, a high performance liquid chromatography (HPLC)
      method has been developed that is rapid, specific and reliable for the
      quantification of reovirus type 3 particles. Using an anion-exchange column, the
      intact virus eluted from the contaminants in 9.78 min at 350 mM NaCl in 50mM
      HEPES, pH 7.10 in a total analysis time of 25 min. The virus demonstrated a
      homogenous peak with no co-elution of other compounds as analyzed by photodiode
      array analysis. The HPLC method facilitated the optimization of the purification
      process which resulted in the improvement of both total and infectious particle
      recovery and contributed to the successful scale-up of the process at the 20 L,
      40 L and 100 L production scale. The method is suitable for the analysis of crude
      virus supernatants, crude lysates, semi-purified and purified preparations and
      therefore is an ideal monitoring tool during process development and scale-up.

PMID- 18632240
TI  - Study of ocular pharmacokinetics of in situ gel system for S(-)-satropane
      evaluated by microdialysis.
AB  - S(-)-Satropane is currently being developed to in situ forming ophthalmic gel, a
      new ophthalmic delivery system, for the treatment of glaucoma. To evaluate the
      pharmacokinetic profiles of S(-)-satropane, the microdialysis method was
      employed. The concentration of S(-)-satropane in dialysates was measured by using
      liquid chromatography/tandem mass spectrometry (LC-MS/MS). Unlike the common
      solution prepared in normal saline, in which the level of S(-)-satropane in
      aqueous humor increased rapidly after instillation and reached the maximal level
      (C(max) of 1.508+/-0.297 microg ml(-1)) within 1h, S(-)-satropane exhibited 3.2
      fold greater C(max) and 2.2-fold greater AUC(0-3h) (p<0.05) in the in situ
      forming gel. The results showed that the in situ forming gel system could improve
      the ocular bioavailability of S(-)-satropane.

PMID- 18632241
TI  - A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm
      repair.
AB  - BACKGROUND: The late durability of endovascular aneurysm repair (EVAR) has been
      limited by progressive aortic degeneration believed to be mediated by matrix
      metalloproteases (MMP). The goal of this study was to evaluate the effect of a
      MMP inhibitor, doxycycline, on EVAR. METHODS: Patients undergoing EVAR were
      randomized to doxycycline (100 mg twice daily) or placebo for 6 months following
      the procedure. Clinical data, blood samples, and computed tomography (CT) scans
      were obtained preoperatively, postoperatively (blood only), and at 1- and 6-month
      follow-up. Forty-four subjects were analyzed based on intention-to-treat.
      RESULTS: Plasma MMP-9 decreased significantly below baseline in the doxycycline
      (N = 20) treated patients at 6 months (-16.4% +/- 20.7%, P < .05) while there was
      a nonsignificant increase in the placebo (N = 24) group (128.1% +/- 73.5%). This
      was primarily related to changes between 1 and 6 months. In patients with
      endoleaks at 6 months, plasma MMP-9 increased in 83% of the placebo treated
      patients, but in only 14% of the doxycycline treated group (P < .03). Among
      endoleak-free patients with AneuRx or Excluder endografts, doxycycline treatment
      resulted in greater decreases in maximum aortic diameter than placebo treatment (
      13.3% +/- 3.3% vs -3.8% +/- 3.0%, P < .05). Furthermore, doxycycline treatment
      significantly reduced the aortic neck dilatation at 6 months in Excluder treated
      patients. CONCLUSION: There is evidence of persistent MMP release representing
      ongoing aortic degradation after endografting which can be inhibited by
      doxycycline therapy. In analyses based on the endograft used, treatment with
      doxycycline also demonstrated evidence of increased aortic dimensional stability,
      a surrogate marker for long-term success of EVAR. Although encouraging, these
      results require confirmation in larger patient populations. Doxycycline should
      undergo more thorough evaluation as a potential adjuvant treatment to improve the
      results of EVAR, particularly in certain subgroups.

PMID- 18632242
TI  - Meta-analysis of endovascular vs open repair for traumatic descending thoracic
      aortic rupture.
AB  - OBJECTIVES: Traumatic thoracic aortic injuries are associated with high mortality
      and morbidity. These patients often have multiple injuries, and delayed aortic
      repair is frequently used. Endoluminal grafts offer an alternative to open
      surgical repair. We performed a meta-analysis of comparative studies evaluating
      endovascular vs open repair of these injuries. METHODS: A systematic search of
      studies reporting treatment of traumatic aortic injury was performed using the
      following databases: Medline/PubMed, CINAHL, Proquest, Up to Date, Database of
      Abstracts of Reviews of Effects (DARE), ClinicalTrials.gov, the Cochrane Central
      Register of Controlled Trials and the Cochrane Database of Systematic Reviews.
      Search terms were thoracic aortic trauma, traumatic thoracic aortic injury,
      traumatic aortic rupture, stent graft repair, and endovascular repair. Outcomes
      analyzed were procedure-related mortality, overall 30-day mortality, and
      paraplegia/paraparesis rate using odds ratios (OR) and 95% confidence intervals
      (CI). Publication bias was investigated using funnel plots. Assessment of
      homogeneity was performed using the Q test; statistical heterogeneity was
      considered present at P < .05. Weighted averages of age, interval to repair, and
      injury severity score were compared with the Welch t test; P < .05 was considered
      statistically significant. RESULTS: Seventeen retrospective cohort studies from
      2003 to 2007 were included. All were nonrandomized; no prospective randomized
      trials were found. These studies reported on 589 patients; 369 were treated with
      open repair, and 220 underwent thoracic stent graft placement. There was no
      significant difference in age (mean 38.8 years for both) or interval to repair
      (mean 1.5 days for endoluminal repair; 1 day for open repair). Injury severity
      score was higher for patients undergoing endoluminal repair (mean, 42.4 vs 37.4
      for open repair, P < .001). Procedure-related mortality was significantly lower
      with endoluminal repair (OR, 0.31; 95% CI, 0.15-0.66; P = .002). Overall 30-day
      mortality was also lower after endoluminal repair (OR, 0.44; 95% CI, 0.25-0.78; P
      = .005). Sixteen studies reported data for postoperative paraplegia; 215 patients
      were treated with endograft placement and 333 with open repair. The risk of
      postoperative paraplegia was significantly less with endoluminal repair (OR,
      0.32; 95% CI, 0.1-0.93; P = .037). The Q test did not indicate significant
      heterogeneity for the outcomes of interest; publication bias was limited.
      CONCLUSIONS: Meta-analysis of retrospective cohort studies indicates that
      endovascular treatment of descending thoracic aortic trauma is an alternative to
      open repair and is associated with lower postoperative mortality and ischemic
      spinal cord complication rates.

PMID- 18632243
TI  - Catheter-less angiography for endovascular aortic aneurysm repair: a new
      application of carbon dioxide as a contrast agent.
AB  - OBJECTIVE: Avoidance of nephrotoxic contrast agents during endovascular repair of
      abdominal aortic aneurysms (EVAR) may reduce the incidence of renal dysfunction
      following the procedure. Carbon dioxide (CO(2)) angiography is a safe alternative
      to iodinated contrast media vastly under-utilized by vascular surgeons. We herein
      describe our experience with a simple angiographic technique using CO(2) for EVAR
      guidance that does not require a separate angiographic catheter. METHODS:
      Eighteen patients underwent EVAR using angiography with CO(2) delivered through
      the endograft sheath. The renal and hypogastric arteries were localized for
      endograft deployment exclusively with CO(2) in all patients. Completion
      angiography was done with CO(2) in all patients and an additional angiogram with
      iodinated media was done in 13 cases. RESULTS: All endograft deployments were
      done successfully with CO(2) angiography injected through the endograft delivery
      systems and femoral access sheaths. Additional iodinated media completion
      angiography did not modify the procedure in any case. All patients were
      discharged within two days after surgery. There were no ischemic or systemic
      complications related to CO(2) administration. Follow-up CT-scan revealed well
      positioned endografts with the expected patent renal and hypogastric arteries in
      all patients, and no additional endoleaks. No significant deterioration in renal
      function occurred in any case. CONCLUSION: Carbon dioxide angiography conducted
      through the endograft delivery sheath is reliable for endograft deployment, safe,
      non-toxic and inexpensive. In addition, it may expedite EVAR by eliminating a
      number of angiographic catheter placements and exchanges during the procedure.
      This favorable experience warrants further utilization of this technique.

PMID- 18632244
TI  - Surgical treatment for patients with different origins of Krukenberg tumors:
      outcomes and prognostic factors.
AB  - AIMS: We sought to investigate survival impacts of metastasectomy in women with
      Krukenberg tumors of the ovary and survival benefits in different origins
      (gastric cancer, colorectal cancer, or others). METHODS: All patients diagnosed
      with Krukenberg tumors of the ovary who underwent surgical treatment at a single
      institution between 1997 and 2003 were retrospectively evaluated. Survival
      analyses and comparisons were performed using Kaplan-Meier method and log-rank
      test. RESULTS: A total of 54 patients with Krukenberg tumors of the ovary were
      identified. The estimated 5-year survival was 12.1%. The median survival in
      patients with microscopic residual disease after metastasectomy was 29.6 months,
      compared to 10 months in those with visible residual disease (P<0.01). The median
      survival among patients with Krukenberg tumors of gastric origin, colon and
      rectum origin, and other origins were 13 months, 29.6 months, and 48.2 months,
      respectively (P=0.03). There was a significant difference in survival between
      patients with metastatic disease confined to the ovaries and those with extensive
      metastases, with an estimated median survival of 30.7 months and 10 months,
      respectively (P=0.02). Multivariate analysis suggested that the origin of ovarian
      metastatic carcinoma (P<0.01), residual disease after metastasectomy (P<0.01),
      and KPS (Karnofsky performance status) (P=0.03) were independent prognostic
      factors of survival. CONCLUSIONS: Patients with Krukenberg tumors from colorectal
      cancer experience a better prognosis than those from gastric cancer and benefit
      more from metastasectomy. And metastasectomy significantly lengthens overall
      survival in patients with primary colorectal or breast cancer, higher KPS score,
      and those with optimal metastasectomy.

PMID- 18632245
TI  - [Pseudomyxoma peritonei].

PMID- 18632246
TI  - [Myocardial revascularization thirty years after: surgery is still up to date].

PMID- 18632247
TI  - [Acute coronary syndrome: an analyse of complications during interhospital
      transports to interventional coronary departments].
AB  - OBJECTIVES: The management of acute coronary syndrome (ACS) has one major
      objective today: early myocardial reperfusion. This results in a growing number
      of interhospital transfers of patients with ACS from general hospitals towards
      hospitals with interventional cardiology departments. This study's aim was to
      analyze the complications during transfers to assess the need for changes in
      transfer procedures. METHOD: Prospective single-center study over 6 months,
      including all patients transferred for ACS (regardless of whether or not they
      were ST+) to an interventional cardiology department. RESULTS: The study included
      48 patients, with an average age of 68 years and a sex ratio of 3 men per woman.
      25% had a complication during transfer, with resumption of pain, dysrhythmia or
      shock. There were no deaths during the course of transfer. 92% of complications
      occurred among patients coming from an emergency unit, compared with 8% coming
      from a cardiology intensive care unit. ACS had begun within the past 24 hours for
      all. DISCUSSION: This high incidence justifies careful medical supervision of
      interhospital transfers for patients with an ACS < 24 hours. No patients
      transferred more than 24 hours after the onset of ACS developed complications.
      Further studies of this type of patient are necessary to determine the needs of
      this group.

PMID- 18632248
TI  - [Nutritional anemias in elderly patients].
AB  - Nutritional deficiencies cause one third of the cases of anemia in the elderly.
      The urgency of anemia management in elderly patients depends on tolerance and
      repercussions, rather than only on the hemoglobin level. Iron, vitamin B12 and
      folate are the most common deficiencies, and their levels should be tested.
      Chronic gastrointestinal bleeding is the principal cause of iron-deficiency
      anemia. Management is based on supplementation combined with effective
      etiological treatment.

PMID- 18632249
TI  - [Cytopenia: high quality clinical research must be encouraged].

PMID- 18632250
TI  - Systematic polymorphism analysis of the CYP2D6 gene in four different
      geographical Han populations in mainland China.
AB  - In this study, we systematically screened the polymorphisms of the whole CYP2D6
      gene in the populations of four different geographical locations in China,
      namely, Shanghai, Shantou, Shenyang, and Xi'an, using a sample of 100 subjects
      from each population. Forty-eight different polymorphisms were detected as well
      as 12 novel ones. One novel nonsynonymous SNP was detected, and one novel
      intronic SNP was revealed that might inactivate a cryptic donor site 392
      nucleotides downstream of the exon 6 natural donor site. In addition, the
      frequencies of some polymorphisms and alleles demonstrated significant
      differences among the four populations. Linkage disequilibrium analysis and tag
      SNP selection were performed separately for each population. Haplotypes were
      analyzed within the selected tag SNPs. Tag SNP selection and haplotype
      distributions showed differences across the four populations. This is the first
      large-scale study to analyze polymorphisms systematically across the whole CYP2D6
      gene in the Chinese Han population.

PMID- 18632251
TI  - Genes required for functional glycosylation of dystroglycan are conserved in
      zebrafish.
AB  - Mutations in human genes encoding proteins involved in alpha-dystroglycan
      glycosylation result in dystroglycanopathies: severe congenital muscular
      dystrophy phenotypes often accompanied by CNS abnormalities and ocular defects.
      We have identified the zebrafish orthologues of the seven known genes in this
      pathway and examined their expression during embryonic development. Zebrafish
      Large, POMT1, POMT2, POMGnT1, Fukutin, and FKRP show in situ hybridization
      patterns similar to those of dystroglycan, with broad expression throughout early
      development. By 30 h postfertilization (hpf), transcripts of all these genes are
      most prominent in the CNS, eye, and muscle, tissues that are predominantly
      affected in the dystroglycanopathies. In contrast, Large2 expression is more
      restricted and by 30 hpf is confined to the lens, cerebellum, and pronephric
      duct. We show that the monoclonal antibody IIH6, which recognizes a glycoform of
      dystroglycan, also detects the zebrafish protein. Injection of morpholino
      oligonucleotides against zebrafish Large2 resulted in loss of IIH6
      immunostaining. These data indicate that the dystroglycan glycosylation pathway
      is conserved in zebrafish and suggest this organism is likely to be a useful
      model system for functional studies.

PMID- 18632252
TI  - Completing a postal health questionnaire did not affect anxiety or related
      measures: randomized controlled trial.
AB  - OBJECTIVE: There is evidence from laboratory studies that anxiety scores are
      elevated by completing questionnaires about health problems for the first time.
      This limits interpretation of the common finding that people receiving risk
      information from screening programs show elevated anxiety (as assessed by
      questionnaire) in the short-term, which subsides over time. We examine the extent
      to which postal questionnaire studies are affected by this potential measurement
      artifact. STUDY DESIGN AND SETTING: Participants were 964 patients at high risk
      of undiagnosed diabetes, registered at five general practices. A two-group
      randomized experimental design was used, with the experimental group (n=484)
      receiving an initial questionnaire concerning screening for diabetes, and the
      control group (n=480) not receiving this questionnaire. Outcomes were assessed by
      an identical questionnaire 3 months later. RESULTS: There were no significant
      differences in questionnaire scores at three months between the two groups on any
      of the outcome measures, including anxiety, symptoms, perceptions of diabetes
      severity, and perceived diabetes risk. CONCLUSION: These results suggest that the
      problems associated with the use of anxiety questionnaires that are found in
      laboratory studies do not occur in postal studies: the observed changes in
      anxiety after receiving screening results are therefore unlikely to be
      artifactual.

PMID- 18632253
TI  - A clinicopathologic study on basaloid squamous cell carcinoma in the oral and
      maxillofacial region.
AB  - Basaloid squamous cell carcinoma (BSCC) is a rare distinct variant of squamous
      cell carcinoma (SCC). To investigate its clinical behavior and prognosis, 15
      patients with BSCC in the oral and maxillofacial region were clinically analyzed
      and compared with 15 patients with conventional SCC matched for site, stage,
      gender and age. To understand its immunohistochemical features, sections for
      cytokeratin AE1/AE3, CK 13. CK 7, CK 8, proliferating cell nuclear antigen (PCNA)
      and p53 were reviewed from 12 patients with BSCC. The rate of cervical lymph node
      metastasis of BSCC was as high as 67% and that of distant metastasis 13%. The
      tumor recurrence rate was 33% and the 3-year and 5-year survival rates were 53%
      and 32%, respectively. For conventional SCC, the cervical lymph node metastasis
      rate was 27%, that of distant metastasis 7%, tumor recurrence rate was 33%, and 3
      year and 5-year survival rates were 80% and 70%, respectively. In most BSCC
      patients (10/12) the PCNA index was over 50%. Twelve BSCC patients were diagnosed
      with grade II or III conventional SCC when the original records of the primary
      diagnosis for the 15 patients with BSCC were reviewed. The biological behavior
      and prognosis of BSCC are similar to those of poorly differentiated SCC.

PMID- 18632254
TI  - Myofascial pain syndromes in the maxillofacial area: a common but underdiagnosed
      cause of head and neck pain.
AB  - Myofascial pain syndromes (MPS) are a large group of muscular disorders,
      characterized by the presence of hypersensitive spots called trigger points (TP).
      The maxillofacial region is a high-frequency area for developing TPs. The aim of
      this paper was to review and summarize the most important methods of management.
      A literature review was carried out from Medline and database sources. A range of
      study types were selected for analysis. TP formation and activity result in a
      reverberating circuit of sustained neural activity. Central mechanisms, primarily
      associated with psychosocial factors, lead to chronicity. Other synergistic
      factors are metabolic disorders, nutritional imbalances and regional anatomic
      disorders. A detailed history and physical examination are important for proper
      diagnosis. The aim of MPS management is pain relief and restoration of full
      muscle function. Treatment may require enhancing central inhibition, using
      pharmacological and/or behavioural techniques, and reducing peripheral inputs,
      using physical therapy. There are various effective methods of inactivation of
      TPs. Recognition and reduction of synergistic factors may be important. MPS have
      a very high prevalence in the general population, despite low awareness among
      physicians, affecting patients' quality of life. There is a need for
      interdisciplinary teams of health professionals to achieve proper diagnosis,
      management and sustainable outcomes.

PMID- 18632255
TI  - Association of SNPs and haplotypes in APOL1, 2 and 4 with schizophrenia.
AB  - Prior work found the APOL1, 2 and 4 genes, located on chromosome 22q12.3-q13.1,
      to be upregulated in brains of schizophrenic patients. We performed a family
      based association study using 130 SNPs tagging the APOL gene family (APOL1-6).
      The subjects were 112 African-American (AA), 114 European-American (EA), 109
      Chinese (Ch) and 42 Japanese (Jp) families with schizophrenia (377 families, 1161
      genotyped members and 647 genotyped affected in total). Seven SNPs had p
      values<0.05 in the APOL1, 2 and 4 regions for the AA, EA and combined (AA and EA)
      samples. In the AA sample, two SNPs, rs9610449 and rs6000200 showed low p-values;
      and a haplotype which comprised these two SNPs yielded a p-value of 0.00029 using
      the global test (GT) and the allele specific test (AST). The two SNPs and the
      haplotype were associated with risk for schizophrenia in African-Americans. In
      the combined (AA and EA) sample, two SNPs, rs2003813 and rs2157249 showed low p
      values; and a three SNP haplotype including these two SNPs was significant using
      the GT (p=0.0013) and the AST (p=0.000090). The association of this haplotype
      with schizophrenia was significant for the entire (AA, EA, Ch and Jp) sample
      using the GT (p=0.00054) and the AST (p=0.00011). Although our study is not
      definitive, it suggests that the APOL genes should be more extensively studied in
      schizophrenia.

PMID- 18632257
TI  - Predicting blood-brain barrier penetration from molecular weight and number of
      polar atoms.
AB  - A simple three-descriptor model to predict blood-brain barrier is derived from a
      training set of 78 compounds: logBB=-9.880 x 10(-6)M(W)(2)+7.339 x 10(-3)M(W)
      0.2268n(pol)-0.1143 (n=78, r(2)=0.74), where logBB is the logarithm of the ratio
      of the steady-state concentration of the compound in the brain to concentration
      in the blood, M(W) is the molecular weight, n(pol) is the number of polar atoms
      (oxygen, nitrogen, and attached hydrogen), n is the number of compounds, and r is
      the correlation coefficient. The model is validated through use of leave-one-out
      procedure and an external test set (25 compounds). The model is suitable for the
      rapid prediction of the blood-brain barrier penetration of drug candidates
      because of its predictive ability and simplicity.

PMID- 18632256
TI  - Attribution style as a factor in psychosis and symptom resolution.
AB  - INTRODUCTION: Attribution (AT) style theory provides a framework for
      understanding the causal explanations that individuals give for their own
      behaviour and the behaviour of others. It has been suggested that patients with
      persecutory delusions excessively attribute hypothetical positive events to
      internal causes (self) and hypothetical negative events to external personal
      causes. Despite this, how AT associates with psychotic symptoms (not only
      persecutory delusions) and how it changes with the resolution of psychosis has
      never been investigated. We conducted a cross-sectional study to investigate how
      AT is associated with psychopathology and a longitudinal study to examine the
      change of AT during the first 6 weeks of antipsychotic treatment and the
      relationship with psychopathology improvement. METHODS: 86 patients meeting DSM
      IV criteria for schizophrenia and related psychotic disorders were included in
      the cross-sectional study, and 17 patients in the longitudinal study. The
      longitudinal group were free of antipsychotic drugs at baseline and followed for
      6 weeks after being started on antipsychotic medication by their psychiatrist. We
      used the Internal, Personal and Situational Attributions Questionnaire (IPSAQ) as
      a measure of AT. RESULTS: Patients that tend to internalize (i.e. less self
      serving bias), showed greater overall psychopathology, as measured by PANSS-Total
      (F(2,83)=6.59, p=0.002), with a trend toward significance for PANSS-Positive
      (F(2,83)=2.62 p=0.07). Longitudinally, having a low self-serving bias was
      associated with poorer response to antipsychotic treatment. Further,
      externalizing bias seems to change early on in treatment (F=9.65 df=1,15 p=0.007)
      and reach ceiling effects thereafter. CONCLUSIONS: AT is related to overall
      symptom severity, with internalizing style linked to higher global
      psychopathology. Antipsychotic treatment has little effect on AT, at least within
      6 weeks of antipsychotic exposure, and only a modest effect is on EB which
      plateaus within 2 weeks. Finally, internalizing style appears associated with
      poorer response to antipsychotic treatment.

PMID- 18632258
TI  - Inflammatory and functional effects of increasing asthma treatment with
      formoterol or double dose budesonide.
AB  - Adding a long-acting beta(2)-agonist to inhaled corticosteroids (ICS) for asthma
      treatment is better than increasing ICS dose in improving clinical status,
      although there is no consensus about the impact of this regimen on inflammation.
      In this double-blind, randomized, parallel group study, asthmatics with moderate
      to severe disease used budesonide (400 mcg/day) for 5 weeks (run-in period); then
      they were randomized to use budesonide (800 mcg/day--BUD group) or budesonide
      plus formoterol (400 mcg and 24 mcg/day, respectively--FORMO group) for 9 weeks
      (treatment period). Home PEF measurements, symptom daily reporting, spirometry,
      sputum induction (for differential cell counts and sputum cell cultures), and
      hypertonic saline bronchial challenge test were performed before and after
      treatments. TNF-alpha, IL-4 and eotaxin-2 levels in the sputum and cell culture
      supernatants were determined. Morning and night PEF values increased in the FORMO
      group during the treatment period (p<0.01), from 435+/-162 to 489+/-169 and 428+/
      160 to 496+/-173 L/min, respectively. The rate of exacerbations in the FORMO
      group was lower than in the BUD group (p<0.05). Neutrophil counts in sputum
      increased in both groups (p<0.05) and leukocyte viability after 48 h-culture
      increased in the FORMO group (p<0.05). No other parameter changed significantly
      in either group. This study showed that adding formoterol to budesonide improved
      home PEF and provided protection from exacerbations, although increase of
      leukocyte viability in cell culture may be a matter of concern and needs further
      investigation.

PMID- 18632259
TI  - Bioreactor treatment of municipal solid waste landfill leachates:
      characterization of organic fractions.
AB  - Quantitative and qualitative changes in organic matter were studied at different
      stages of treatment in a bioreactor designed to process leachates from a
      municipal solid waste landfill. The particulate matter (PM) and macromolecular
      fractions of the dissolved organic matter with solubility properties comparable
      to humic (acid-insoluble) and fulvic (acid-soluble) acid fractions (AI, AS,
      respectively) from the incoming black liquid, the bioreactor content, and the
      final processed effluent were isolated, quantified, and characterized by visible
      and infrared (IR) spectroscopies. The macromolecular signature either aliphatic
      (glycopeptides, carbohydrates) or aromatic (coinciding with infrared patterns of
      lignin, tannins etc.) enabled us to characterize the different organic fractions
      during the course of microbial transformation. The results reveal significant
      changes in the nitrogen speciation patterns within the different organic
      fractions isolated from the wastewater. The final increase in the relative
      proportions of nitrogen in the least aromatic AS fraction during microbial
      transformation could be related to protein formation inside the bioreactor. After
      biological treatment and ultrafiltration, the amount of organic matter was
      reduced by approximately 70%, whereas aromaticity increased in all fractions,
      indicating preferential elimination of aliphatic wastewater compounds. Most of
      the remaining fractions at the end of the process consisted of a yellow residue
      rich in low molecular weight AS fractions.

PMID- 18632260
TI  - Detection of clinically relevant levels of protein analyte under physiologic
      buffer using planar field effect transistors.
AB  - Electrochemical detection of protein binding at physiological salt concentration
      by planar field effect transistor platforms has yet to be documented
      convincingly. Here we report detection of streptavidin and clinically relevant
      levels of biotinylated monokine induced by interferon gamma (MIG) at
      physiological salt concentrations with AlGaN heterojunction field effect
      transistors (HFETs). The AlGaN HFETs are functionalized with a silane linker and
      analyte-specific affinity elements. Polarity of sensor responses is as expected
      from n-type HFETs to negatively and positively charged analytes. Sensitivity of
      the HFET sensors increases when salt concentration decreases, and the devices
      also exhibit dose-dependent responses to analyte. Detection of clinically
      relevant MIG concentrations at physiological salt levels demonstrates the
      potential for AlGaN devices to be used in development of in vivo biosensors.

PMID- 18632261
TI  - Audit of performance of needle core biopsy diagnoses of screen detected breast
      lesions.
AB  - Breast needle core biopsy (NCB) is now a standard diagnostic procedure in the
      triple assessment of screen detected breast lesions. Therefore, it is important
      to provide robust and up-to-date data on the performance of NCB in the screening
      setting. However, previous studies of NCB have suffered from either limitation in
      the number of assessed cases or included a mix of symptomatic and screen detected
      breast lesions. In this study, we have evaluated the performance of a large
      series of uniformly assessed NCBs of screen detected lesions (20001 cases) over a
      period of 10 years (1997-2007). Our results showed a gradual increase in the
      number of NCBs and an improvement of their performance over the period of the
      study; absolute sensitivity increased from 84.9% to 96.4% and complete
      sensitivity increased from 90.9% to 99.7%. There was also a gradual reduction in
      the number of surgical interventions after benign (B2) and negative (B1) NCB
      diagnoses. Our study provides data showing variance from the suggested thresholds
      for the measures of performance of NCB in the United Kingdom which could be used
      to provide updated evidence-based thresholds for assessment of performance of NCB
      diagnosis use in the assessment of breast cancer screen detected lesions in the
      UK and elsewhere.

PMID- 18632262
TI  - Imaging liver metastases of colorectal cancer patients with radiolabelled
      bevacizumab: Lack of correlation with VEGF-A expression.
AB  - AIM OF THE STUDY: To investigate the correlation between tumour accumulation of
      In-111-bevacizumab and VEGF-A expression in patients with colorectal liver
      metastases. METHODS: Two weeks before resection of the liver metastases 12
      patients were intravenously injected with In-111-labelled bevacizumab. Ten
      minutes and 7 d after injection a whole body scan was acquired. Seven days after
      the injection, 3D acquisition SPECT of the liver was performed. RESULTS: Enhanced
      uptake of In-111-bevacizumab in the liver metastases was observed in 9 of the 12
      patients. The level of antibody accumulation in these lesions varied
      considerably. There was no correlation between the level of In-111-antibody
      accumulation and the level of VEGF-A expression in the tissue as determined by in
      situ hybridisation and ELISA. CONCLUSIONS: In this study, we investigated the
      correlation between tumour accumulation of radiolabelled bevacizumab and VEGF-A
      expression in patients with colorectal liver metastases. No clear-cut correlation
      between the level of antibody accumulation and expression of VEGF-A was found.

PMID- 18632263
TI  - Truncation of the cellulose binding domain improved thermal stability of endo
      beta-1,4-glucanase from Bacillus subtilis JA18.
AB  - The C-terminus region of endo-beta-glucanase Egl499 from Bacillus subtilis JA18
      was suggested to be a putative family 3 cellulose-binding domain (CBD) by
      computer analysis. To prove this proposal, C-terminus truncation mutant Egl330
      was constructed and expressed. Compared with Egl499, Egl330 lost the cellulose
      binding capability at 4 degrees C, confirming the C-terminus region was a CBD.
      Binding of the CBD to Avicel was inhibited by carboxymethylcellulose (CMC), but
      not by barley beta-glucan and glucose at concentration of 0.1% and 0.5%. Kinetic
      analysis showed both the turnover rate (k(cat)) and the catalytic efficiency
      (k(cat)/K(m)) of Egl330 increased for the substrate CMC compared to Egl499. A
      great improvement in thermal stability was observed in Egl330. The half life of
      Egl330 at 65 degrees C increased to three folds that of Egl499, from 10 to 29
      min. After treated at 80 degrees C for 10 min, Egl330 could recover more than 60%
      of its original activity while Egl499 only recovered 12% activity. UV
      spectrometry analysis showed Egl330 and Egl499 differed in refolding efficiency
      after heat treatment.

PMID- 18632264
TI  - Changes in microbial biomass and P fractions in biogenic household waste compost
      amended with inorganic P fertilizers.
AB  - The present study was conducted to evaluate the changes in microbial biomass
      indices (C, N, and especially P) and in P fractions in compost amended with
      inorganic P fertilizers. In the non-amended control, the average contents of
      microbial biomass C, N, and P were 1744, 193, and 63 microg g(-1) compost,
      respectively. On average, 1.3% of total P was stored as microbial biomass P. The
      addition of KH(2)PO(4) and TSP (triple super phosphate) led to immediate
      significant increases in microbial biomass C, N, and P. Approximately, 4.6% of
      the added TSP and 5.8% of the added KH(2)PO(4) were incorporated on average into
      the microbial biomass throughout the incubation. Approximately, 4.7% of the 1mg
      and 5.8% of the 2mg addition rate were incorporated on average into the microbial
      biomass. In the amendment treatments, the average contents of microbial biomass
      C, N, and P declined by 44%, 64%, and 49%, respectively. Initially, the average
      size of the P fractions in the non-amended compost increased in the order (% of
      total P in brackets) resin P (0.7%)<NaOH-extractable P(i) (inorganic P,
      3.0%)<NaOH-P(o) (organic P, 6.9%)<NaHCO(3)-P(i) (11.9%)<NaHCO(3)-P(o)
      (17.0%)<residual P (24.6%)<HCl-P (35.7%). Initially, the relative contributions
      of the P fractions in the amended compost treatments increased in the order: NaOH
      P(i) (1.0%)<resin P (2.5%)<NaOH-P(o) (4.5%)<NaHCO(3)-P(o) (4.9%)<residual P
      (14.8%)<HCl-P (15.2%)<NaHCO(3)-P(i) (57.1%). At the end of the 56-day incubation,
      the largest and highly soluble fraction of NaHCO(3)-extractable P(i) had
      decreased in place of the less soluble fractions NaOH-extractable P(i) and P(o),
      but especially HCl-P, but not in place of the insoluble fraction of residual P.
      The microbial biomass is able to rapidly store significant amounts of easily
      soluble P and to prevent it from adsorption or other fixation processes.

PMID- 18632265
TI  - Construction a hybrid biosorbent using Scenedesmus quadricauda and Ca-alginate
      for biosorption of Cu(II), Zn(II) and Ni(II): kinetics and equilibrium studies.
AB  - The potential use of the immobilized fresh water algae (in Ca-alginate) of
      Scenedesmus quadricauda to remove Cu(II), Zn(II) and Ni(II) ions from aqueous
      solutions was evaluated using Ca-alginate beads as a control system. Ca-alginate
      beads containing immobilized algae were incubated for the uniform growth at 22
      degrees C for 5d ays. Adsorption of Cu(II), Zn(II) and Ni(II) ions on the
      immobilized algae showed highest values at around pH 5.0. Adsorption of Cu(II),
      Zn(II) and Ni(II) ions on the immobilized algae increased as the initial
      concentration of metal ions increased in the medium. The maximum adsorption
      capacities of the immobilized algal biosorbents for Cu(II), Zn(II) and Ni(II)
      were 75.6, 55.2 and 30.4 mg/g (or 1.155, 0.933 and 0.465 mmol/g) biosorbent,
      respectively. When the heavy metal ions were in competition, the amounts of
      adsorbed metal ions were found to be 0.84 mol/g for Cu(II), 0.59 mol/g for Ni(II)
      and 0.08 mol/g for Zn(II), the immobilised algal biomass was significantly
      selective for Cu(II) ions. The adsorption-equilibrium was also represented with
      Langmuir, Freundlich and Dubinin-Radushkevich adsorption isotherms. The
      adsorption of Cu(II), Zn(II) and Ni(II) ions on the immobilized algae followed
      second-order kinetic.

PMID- 18632266
TI  - Enzymatic saccharification of woody biomass micro/nanofibrillated by continuous
      extrusion process I--effect of additives with cellulose affinity.
AB  - Mechanical micro/nanofibrillation of Douglas fir was performed by a continuous
      extrusion process in an attempt to develop a cost-effective pretreatment method
      for enzymatic saccharification. Additives with cellulose affinity (ethylene
      glycol, glycerol, and dimethyl sulfoxide) were used to effectively fibrillate the
      wood cell wall into submicron- or nano-scale, thus opening up the cell wall
      structure for improving enzymatic accessibility, and lower the extrusion torque.
      Morphological characterization showed that ethylene glycol was the most effective
      additive for fibrillation. The fibrillated products were converted into glucose
      with a high yield by enzymatic saccharification. The maximum cellulose-to-glucose
      conversion was achieved when ethylene glycol was used; the value was 62.4%. The
      glucose yield was approximately 6 times higher than that of the untreated raw
      material.

PMID- 18632267
TI  - Aerobic selectors in slaughterhouse activated sludge systems: a preliminary
      investigation.
AB  - Filamentous bulking at a slaughterhouse activated sludge treatment plant
      significantly reduced mixed liquor settling properties, which caused many
      operational problems and worsening in effluent quality. The main cause of this
      condition was attributed to significant levels of influent readily biodegradable
      COD, which was present primarily in the form of organic acids. An aerobic
      selector was chosen to eradicate the usual bulking incidents of slaughterhouse
      wastewater treatment plants. Other plant enhancements included increased aeration
      batch reactor volume, and provision of step feed capability. Comparison of data
      before and after aerobic selector installation showed a significant improvement
      in mixed liquor settleability, which eradicated the need for chemicals that had
      been used to control filaments and to control effluent solids loss. The
      additional volume of the aeration and chemicals eliminations from the activated
      sludge system also served to eliminate aquatic toxicity in the treated effluent.

PMID- 18632268
TI  - Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1
      reverse transcriptase.
AB  - A series of benzyl pyridazinones were evaluated as HIV-1 non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). Several members of this series showed good
      activity against the wild-type virus and NNRTI-resistant viruses. The binding of
      inhibitor 5a to HIV-RT was analyzed by surface plasmon resonance spectroscopy.
      Pharmacokinetic studies of 5a in rat and dog demonstrated that this compound has
      good oral bioavailability in animal species. The crystal structure of a complex
      between HIV-RT and inhibitor 4c is also described.

PMID- 18632269
TI  - Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors.
AB  - A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has
      been identified via molecular scaffold manipulation. Preliminary structure
      activity relationship (SAR) studies led to the discovery of potent, and orally
      bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3
      (methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo
      activity with dose-dependent desaturation index lowering effects.

PMID- 18632270
TI  - Structure-activity relationships of 2-aryl-1H-indole inhibitors of the NorA
      efflux pump in Staphylococcus aureus.
AB  - The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been
      achieved via Pd- or Rh-mediated methodologies, or selective electrophilic
      substitution. All three methods were based on elaborations from simple indole
      precursors. SAR studies on these indoles and 2-phenyl-1H-indole in Staphylococcus
      aureus as NorA efflux pump inhibitors indicated 5-nitro-2-(3
      methoxycarbonyl)phenyl-1H-indole was a slightly more potent inhibitor than the
      lead INF55. A promising new antibacterial lead compound against S. aureus (2
      phenyl-1H-indol-5-yl)-methanol, was also found.

PMID- 18632271
TI  - Endotracheal suctioning of the adult intubated patient--what is the evidence?
AB  - Intubated patients may be unable to adequately cough up secretions. Endotracheal
      suctioning is therefore important in order to reduce the risk of consolidation
      and atelectasis that may lead to inadequate ventilation. The suction procedure is
      associated with complications and risks including bleeding, infection,
      atelectasis, hypoxemia, cardiovascular instability, elevated intracranial
      pressure, and may also cause lesions in the tracheal mucosa. The aim of this
      article was to review the available literature regarding endotracheal suctioning
      of adult intubated intensive care patients and to provide evidence-based
      recommendations The major recommendations are suctioning only when necessary,
      using a suction catheter occluding less than half the lumen of the endotracheal
      tube, using the lowest possible suction pressure, inserting the catheter no
      further than carina, suctioning no longer than 15s, performing continuous rather
      than intermittent suctioning, avoiding saline lavage, providing hyperoxygenation
      before and after the suction procedure, providing hyperinflation combined with
      hyperoxygenation on a non-routine basis, always using aseptic technique, and
      using either closed or open suction systems.

PMID- 18632272
TI  - Effectiveness of an electro-tactile vestibular substitution system in improving
      upright postural control in unilateral vestibular-defective patients.
AB  - We investigated the effects of an electro-tactile vestibular substitution system
      (EVSS) on upright postural control in 12 unilateral vestibular-defective
      patients. The underlying principle of this system consists in supplying the user
      with additional information about his/her head orientation/motion with respect to
      gravitational vertical, normally provided by the vestibular system, through
      electro-tactile stimulation of his/her tongue. Subjects were asked to stand as
      immobile as possible with their eyes closed in two No-EVSS and EVSS conditions.
      Reduced centre-of-foot pressure displacements were observed in the EVSS relative
      to the No-EVSS condition. These results, demonstrating the effectiveness of the
      EVSS system in improving upright postural control in unilateral vestibular
      defective patients, could have implications in clinical and rehabilitative areas.

PMID- 18632273
TI  - Effects of external loads on balance control during upright stance: experimental
      results and model-based predictions.
AB  - The purpose of this study was to identify the effects of external loads on
      balance control during upright stance, and to examine the ability of a new
      balance control model to predict these effects. External loads were applied to 12
      young, healthy participants, and effects on balance control were characterized by
      center-of-pressure (COP) based measures. Several loading conditions were studied,
      involving combinations of load mass (10% and 20% of individual body mass) and
      height (at or 15% of stature above the whole-body COM). A balance control model
      based on an optimal control strategy was used to predict COP time series. It was
      assumed that a given individual would adopt the same neural optimal control
      mechanisms, identified in a no-load condition, under diverse external loading
      conditions. With the application of external loads, COP mean velocity in the
      anterior-posterior direction and RMS distance in the medial-lateral direction
      increased 8.1% and 10.4%, respectively. Predicted COP mean velocity and RMS
      distance in the anterior-posterior direction also increased with external
      loading, by 11.1% and 2.9%, respectively. Both experimental COP data and model
      based predictions provided the same general conclusion, that application of
      larger external loads and loads more superior to the whole body center of mass
      lead to less effective postural control and perhaps a greater risk of loss of
      balance or falls. Thus, it can be concluded that the assumption about consistency
      in control mechanisms was partially supported, and it is the mechanical changes
      induced by external loads that primarily affect balance control.

PMID- 18632274
TI  - Did cathelicidins, a family of multifunctional host-defense peptides, arise from
      a cysteine protease inhibitor?
AB  - Cystatins, the cysteine protease inhibitors, and the cathelin-like domain (CLD)
      of the antimicrobial cathelicidins are classified into the same superfamily
      because of their overall structural similarity. However, their evolutionary
      relationship has remained obscure owing to low sequence similarity. Structural
      similarity of two proteins often provides evidence for divergent evolution;
      however, structural convergence can not be completely ruled out in this case.
      Conserved gene structure and related function provide new evidence in favor of a
      common ancestral origin for cystatins and CLDs. On the basis of two observations,
      the C-terminal location of the cathelicidin antimicrobial domain and evolutionary
      gain of one 3' intron, I propose a gradual evolution model to explain how the AMD
      evolved from the ancestral cystatin scaffold.

PMID- 18632275
TI  - Synthesis, inhibitory activities, and QSAR study of xanthone derivatives as alpha
      glucosidase inhibitors.
AB  - Xanthones and their derivatives have been reported to exhibit strong inhibitory
      activities toward alpha-glucosidase. To provide deep insight into the correlation
      between inhibitory activities and structures of xanthones, multiple linear
      regression (MLR) method was employed to establish QSAR models for 43 xanthone
      derivatives that have diverse structures. Among the 38 typical descriptors
      investigated, Hs (number of H-bond forming substituents), N(pi) (number of
      aromatic rings), and S (softness value) can be utilized to model the inhibitory
      activity. Thus, inhibitory activities of xanthone derivatives can be regulated by
      H-bond forming substituents, pi-stacking-forming aromatic rings and softness
      values on the xanthone skeleton. The accuracy and predictive power of the
      proposed QSAR model were verified by LOO validation, Y-randomization, and test
      group validation with newly synthesized xanthone derivatives.

PMID- 18632276
TI  - Major sperm protein as a diagnostic antigen for onchocerciasis.
AB  - Onchocerciasis, also known as river blindness, is the second leading infectious
      cause of blindness worldwide. In order to successfully control this disease, the
      development of efficient diagnostic tools as well as effective treatments is
      imperative. A number of proteins have been proposed as vaccine and diagnostic
      candidates, yet none have been successfully advanced to the point of general
      clinical use. We have prepared major sperm protein 2 (MSP2) from Onchocerca
      volvulus as a possible diagnostic antigen for onchocerciasis. Importantly,
      recombinant MSP2 is dimeric in solution, identical to alpha-MSP from the
      roundworm, Ascaris suum. A panel of sera obtained from Cameroonian individuals
      afflicted with onchocerciasis positively responded to the recombinant MSP2. Our
      data suggest that MSP2, like the previously described antigen Ov16, can be
      utilized as a diagnostic onchocerciasis antigen for monitoring the interruption
      of transmission.

PMID- 18632277
TI  - Epifluorescence and light microscopy evidencing structural and functional
      polymorphism of ribosomal DNA in fish (Teleostei: Astyanax fasciatus).
AB  - New karyotypic data are presented for the Astyanax fasciatus species complex from
      four different locations on the Upper Tibagi River in the state of Parana,
      Brazil. Chromosome markers were analyzed using conventional (Ag-NOR) and
      molecular (FISH with 18S biotinylated probes) methods. Two cytotypes were found
      in cell counts with diploid number 2n=48 chromosomes and 2n=50 chromosomes,
      previously denominated Cytotype A and B, respectively. Two specific patterns of
      Ag-NORs markers (ribosomal gene activity) were found, with intra-population and
      inter-population variations. Cytotype A exhibited two to three chromosomes with
      NOR sites in the metaphases analyzed. In Cytotype B specimens, up to three
      markers were found, demonstrating greater intra-population and inter-population
      variation. All individuals with only one chromosome pair with NORs were located
      in the telomeric region of the short arm of Chromosome 5. This characteristic was
      interpreted as ancestral for the species. Another identified pattern revealed a
      site in the telomeric region probably in the long arm of Chromosome 4 and another
      submetacentric chromosome with bitelomeric marks exclusively in specimens with
      2n=50 chromosomes. In the FISH analysis (ribosomal gene structure), five to seven
      markers were identified in Cytotype A and three to seven markers were identified
      in Cytotype B. Structural chromosome events and/or transposable elements are
      required to explain the ribosomal gene location diversity in these organisms. The
      results of the present study corroborate the hypothesis that the A. fasciatus of
      the Upper Tibagi River region constitute a species complex.

PMID- 18632278
TI  - Radium-228 analysis of natural waters by Cherenkov counting of Actinium-228.
AB  - The activities of (228)Ra in natural waters were determined by the Cherenkov
      counting of the daughter nuclide (228)Ac. The radium was pre-concentrated on
      MnO(2) and the radium purified via ion exchange and, after a 2-day period of
      incubation to allow for secular equilibrium between the parent-daughter
      (228)Ra((228)Ac), the daughter nuclide (228)Ac was isolated by ion exchange
      according to the method of Nour et al. [2004. Radium-228 determination of natural
      waters via concentration on manganese dioxide and separation using Diphonix ion
      exchange resin. Appl. Radiat. Isot. 61, 1173-1178]. The Cherenkov photons
      produced by (228)Ac were counted directly without the addition of any
      scintillation reagents. The optimum Cherenkov counting window, sample volume, and
      vial type were determined experimentally to achieve optimum Cherenkov photon
      detection efficiency and lowest background count rates. An optimum detection
      efficiency of 10.9+/-0.1% was measured for (228)Ac by Cherenkov counting with a
      very low Cherenkov photon background of 0.317+/-0.013cpm. The addition of sodium
      salicylate into the sample counting vial at a concentration of 0.1g/mL yielded a
      more than 3-fold increase in the Cherenkov detection efficiency of (228)Ac to
      38%. Tests of the Cherenkov counting technique were conducted with several water
      standards of known activity and the results obtained compared closely with a
      conventional liquid scintillation counting technique. The advantages and
      disadvantages of Cherenkov counting compared to liquid scintillation counting
      methods are discussed. Advantages include much lower Cherenkov background count
      rates and consequently lower minimal detectable activities for (228)Ra and no
      need for expensive environmentally unfriendly liquid scintillation cocktails. The
      disadvantages of the Cherenkov counting method include the need to measure
      (228)Ac Cherenkov photon detection efficiency and optimum Cherenkov counting
      volume, which are not at all required when liquid scintillation analysis is used.

PMID- 18632279
TI  - Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats
      by blocking astrocytic IL-1beta production.
AB  - An enhanced production of IL-1beta in glia is a typical feature of epileptogenic
      tissue in experimental models and in human drug-refractory epilepsy. We show here
      that the selective inhibition of Interleukin Converting Enzyme (ICE), which
      cleaves the biologically active form of IL-1beta using VX-765, blocks kindling
      development in rats by preventing IL-1beta increase in forebrain astrocytes,
      without interfering with glia activation. The average afterdischarge duration was
      not altered significantly by VX-765. Up to 24 h after kindling completion and
      drug washout, kindled seizures could not be evoked in treated rats. VX-765 did
      not affect seizures or afterdischarge duration in fully kindled rats. These data
      indicate an antiepileptogenic effect mediated by ICE inhibition and suggest that
      specific anti-IL-1beta pharmacological strategies can be envisaged to interfere
      with epileptogenic mechanisms.

PMID- 18632281
TI  - Chronic type A dissection of the ascending aorta.

PMID- 18632280
TI  - Benefits and risks of intranigral transplantation of GABA-producing cells
      subsequent to the establishment of kindling-induced seizures.
AB  - Neural transplantation has been investigated experimentally and clinically for
      the purpose of developing new treatment options for intractable epilepsy. In the
      present study we assessed the anticonvulsant efficacy and safety of bilateral
      allotransplantation of genetically engineered striatal GABAergic rat cell lines
      into the substantia nigra pars reticulata (SNr). Rats with previously-established
      seizures, induced by amygdala kindling, were used as a model of temporal lobe
      epilepsy. Three cell lines were transplanted: (1) immortalized GABAergic cells
      (M213-2O) derived from embryonic rat striatum; (2) M213-2O cells (CL4)
      transfected with human GAD67 cDNA to obtain higher GABA synthesis than the parent
      cell line; and (3) control cells (121-1I), also derived from embryonic rat
      striatum, but which did not show GAD expression. A second control group received
      injections of medium alone. Transplantation of M213-2O cells into the SNr of
      kindled rats resulted in significant but transient anticonvulsant effects.
      Neither control cells nor medium induced anticonvulsant effects. Strong tissue
      reactions were, however, induced in the host brain of kindled but not of non
      kindled rats, and only in animals that received grafts of genetically modified
      CL4 cells. These tissue reactions included graft rejection, massive infiltration
      of inflammatory immune cells, and gliosis. The anticonvulsant effect of M213-2O
      cells emphasizes the feasibility of local manipulations of seizures by
      intranigral transplantation of GABA-producing cells. On the other hand, the
      present data suggest that kindling-induced activation of microglia in the SNr can
      enhance immune reactions to transplanted cells. In this case, under conditions of
      further immunological stimulation by CL4 cells, transfected with a human cDNA,
      substantial immune reactions occurred. Thus, it appears that the condition of the
      host brain and the production of foreign proteins by transplanted cells have to
      be considered in estimating the risks of rejection of transplants into the brain.

PMID- 18632282
TI  - A comparative study on in vitro and in vivo effects of topical vasodilators in
      human internal mammary, radial artery and great saphenous vein.
AB  - OBJECTIVE: As an important prognostic factor of coronary artery bypass grafting
      (CABG), graft vasospasm can be observed in all currently used graft conduits.
      Radial artery (RA) vasospasm is more prone to occur in comparisons with internal
      mammary artery (IMA) and great saphenous vein (GSV). There is still controversy
      about which antispasmodic agent is superior to different grafts, especially to RA
      conduits. The aim of this pilot study was to investigate the relaxation response
      of four topical vasodilators to different in vitro grafts and how these
      vasodilators affect the blood flow of the vessel in situ during RA harvesting.
      MATERIALS AND METHODS: Vasodilatory properties of diltiazem, nitroglycerin,
      urapidil and nicorandil were compared in matched patient-specific segments of RA,
      IMA and GSV harvested from 12 patients. The vasodilatory response of the RA to
      intraradial administration of nitroglycerin, diltiazem and urapidil was compared
      in vivo (n=10 per group) by assessing the free blood flow of RA. RESULTS: (1) The
      maximal relaxations occurring with urapidil, nitroglycerin and nicorandil in IMA,
      RA and SGV were significantly greater than that with diltiazem. The reactivity of
      all three graft conduits showed similar relaxation with nitroglycerin or with
      diltiazem, but the relaxation with urapidil in RA showed greater than that of IMA
      and GSV, and RA and GSV showed greater relaxation with nicorandil than IMA. (2) A
      dose of 10(-5)mol/l of nitroglycerin, urapidil and nicorandil but not diltiazem
      significantly inhibited the RA response to PE. (3) In vivo, urapidil and
      nitroglycerin significantly increased the RA blood flow, the potency of which was
      greater than that caused by diltiazem. CONCLUSIONS: (1) Comparing with
      nicorandil, urapidil and diltiazem, nitroglycerin caused a significant relaxation
      in all three graft vessels tested. (2) Nitroglycerin, nicorandil and urapidil
      were more effective in preventing RA spasm than diltiazem.

PMID- 18632283
TI  - Combined chemo-radiotherapy for locally advanced non-small cell lung cancer:
      current status and future development.
AB  - Currently, combinations of chemotherapy and radiotherapy are the standard
      treatment approach for locally advanced NSCLC patients. Concomitant chemo
      radiotherapy, although associated with increased acute toxicity, has demonstrated
      to be the better strategy over sequential chemoradiotherapy, and it is to be
      considered a standard approach in patients with good performance status (0-1).
      However, the approach to locally advanced NSCLC and to chemo-radiotherapy
      regimens remains heterogeneous among oncologists, and clinical outcomes are yet
      disappointing. Thus, the search of new strategies is mandatory. The main fields
      of research aiming at improving the survival of locally advanced NSCLC patients
      are: the addition of further combination chemotherapy as induction or
      consolidation to concurrent chemo-radiotherapy, and the integration of
      molecularly targeted therapies into conventional chemo-radiotherapy regimens.

PMID- 18632284
TI  - Mast cells and cancer--no longer just basic science.
AB  - The incorporation of new anti-cancer kinase inhibitors within cancer management
      is rapidly increasing. Mast cells are sensitive to several of these new anti
      cancer agents most notably to c-Kit inhibitors. As a result, studies
      investigating the role of mast cells in tumors may have direct clinical relevance
      and consequently, important clinical implications. Here we review some of the
      basic attributes of mast cells, especially those related to the new "targeted"
      drugs. Mast cell roles such as modulators of regulatory T-cells, inducers of
      angiogenesis and promoters of clot formation are discussed. We also review recent
      mouse tumor models and human pathological data which implicate mast cells as
      having both pro- and anti-tumor growth properties. These studies expose a
      complex, emerging picture of mast cell involvement in tumor biology. It seems
      that mast cell modulator drugs may improve the efficacy of anti-tumor therapy
      under certain circumstances, whilst under others, may negatively affect drug
      efficacy.

PMID- 18632285
TI  - The state of the art.
AB  - Graphical representation of molecular and cellular features is a key form of
      communication in structural biology in which abstract symbols of an economical
      and visually appropriate kind, pseudo-color coding, and dynamic animations all
      play their parts. Accordingly, it should not be surprising that many structural
      biologists--like traditional biologists before them--are talented artists who
      also express themselves on "non-scientific" topics. This article illustrates the
      approaches of and pictures by several practicing scientist-artists-mainly, in
      this sampling, electron microscopists.

PMID- 18632286
TI  - Level of agency in sub-clinical checking.
AB  - This study examined cognitive representations of routine action, through the
      assessment of level of agency, in individuals with sub-clinical checking. The
      level of agency stems from Action Identification Theory [Vallacher, R. R.,
      Wegner, D. M. (1989). Levels of personal agency: Individual variation in action
      identification. Journal of Personality and Social Psychology 57, 660-671], which
      states that how actions are usually identified (based on instrumental aspects or
      purpose) reflects the predominant accessibility of internal representation
      (movements executed vs. goal pursued). Furthermore, this framework proposed that
      altered action regulation is related to low-level of agency (i.e., action
      identification at an instrumental level). In the current study, the main result
      indicated that checking symptoms were related to a low-level of agency, that is,
      individuals with sub-clinical checking identified habitual actions on the basis
      of instrumental aspects. This seems to indicate that checkers may act with a lack
      of goal representations. The results are discussed in terms of the role of low
      level of agency in checking phenomena and related cognitive dysfunction.

PMID- 18632287
TI  - Fast quantitative mapping of absolute water content with full brain coverage.
AB  - Quantitative mapping of water content, especially in the human brain, has the
      potential to provide important information for the study and diagnosis of
      diseases associated with a focal or global change in tissue water homeostasis. In
      the current work, an imaging method for the precise and accurate quantification
      of tissue water content is presented. The method allows the acquisition of water
      content maps with voxel dimensions of 1x1x2 mm(3) and full brain coverage in less
      than 10 min on a standard clinical 1.5 T scanner. The precision was optimised for
      human brain imaging and possible sources of systematic error were carefully
      investigated, demonstrating the ability of the method to quantify water content
      with high accuracy and precision. The approach was validated in phantom
      experiments and quantitative cerebral water content maps of a group of 10 healthy
      volunteers were obtained.

PMID- 18632288
TI  - Frequency specificity of functional connectivity in brain networks.
AB  - Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI)
      signal have been shown to be associated with electroencephalography (EEG) power
      fluctuations in multiple brain networks within predefined frequency bands.
      However, it remains unclear whether frequency-specific characteristics exist in
      the resting-state fMRI signal. In this study, fMRI signals in five functional
      brain networks (sensorimotor, 'default mode', visual, amygdala, and hippocampus)
      were decomposed into various frequency bands within a low-frequency range (0-0.24
      Hz). Results show that the correlations in cortical networks concentrate within
      ultra-low frequencies (0.01-0.06 Hz) while connections within limbic networks
      distribute over a wider frequency range (0.01-0.14 Hz), suggesting distinct
      frequency-specific features in the resting-state fMRI signal within these
      functional networks. Moreover, the connectivity decay rates along the frequency
      bands are positively correlated with the physical distances between connected
      brain regions and seed points. This distance-frequency relationship might be
      attributed to a larger attenuation of synchrony of brain regions separated with
      longer distance and/or connected with more synaptic steps.

PMID- 18632289
TI  - Are you my mother? Phylogenetic analysis reveals orphan hybrid stick insect genus
      is part of a monophyletic New Zealand clade.
AB  - The hybrid stick insect genus Acanthoxyla Uvarov 1944 is unusual for an obligate
      parthenogen, in the extreme morphological diversity it exhibits that has led to
      eight species being recognised. The New Zealand sexual species Clitarchus hookeri
      [White, A. 1846. The zoology of the Voyage of H.M.S. Erebus and Terror. In: 1
      Insects of New Zealand. E.W. Janson, London.] is the putative parental species in
      the hybridization that gave rise to the hybrid lineage Acanthoxyla. In an effort
      to identify the maternal ancestor of Acanthoxyla we sequenced nuclear 28S rDNA
      and/or mtDNA COI & COII of all nine endemic New Zealand stick insect genera,
      representing 17 of the 22 described species. We also sequenced 28S from eight non
      New Zealand stick insects to supplement published 28S sequence data that provided
      a taxonomically and geographically broad sampling of the phasmids. We applied a
      novel search algorithm (SeqSSi=Sequence Similarity Sieve) to assist in selection
      of outgroup taxa for phylogenetic analysis prior to alignment. Phylogenetic
      reconstructions resolved an exclusively New Zealand clade to which the maternal
      lineage of Acanthoxyla belonged, but did not support existing higher level
      taxonomy of stick insects. We did not find a sexual maternal species for
      Acanthoxyla but phylogenetic relationships indicate that this species lived in
      New Zealand and could be classified among the New Zealand Phasmatinae. Among the
      available taxa, the nearest evolutionary neighbours to the New Zealand phasmid
      fauna as a whole were predominantly from the New Zealand region (Fiji, Australia,
      New Guinea, New Caledonia and South America). As it appears to be an orphan, it
      is interesting to speculate that a combination of parthenogenetic reproduction
      and/or hybrid vigour in Acanthoxyla may have contributed to the extinction of its
      mother.

PMID- 18632290
TI  - Calcific tendinitis at the radial insertion of the biceps brachii: a case report.

PMID- 18632291
TI  - Operative treatment of a winged scapula due to peripheral nerve palsy in Lyme
      disease: a case report and review of the literature.

PMID- 18632292
TI  - Developmental changes in insulin-like growth factor (IGF)-I and -II mRNA
      abundance in extra-embryonic membranes and small intestine of avian embryos.
AB  - OBJECTIVE: Numerous researchers have evaluated the insulin-like growth factors
      (IGF) influence on mammalian fetal development. Although IGF has been explored in
      the avian system, questions remain on the role of IGF in avian development.
      Therefore, the current study evaluated the mRNA abundance of IGF in the amnion
      and allantoic membranes and developing small intestine in the chicken, duck, and
      turkey during the incubation and post-hatch period. DESIGN: Broiler, duck, and
      turkey eggs were incubated with small intestinal, allantoic, and amniotic
      membranes collected in the final days of incubation and 1 week post-hatch. RNA
      was extracted using Trizol and qRT-PCR was utilized to compare differences during
      embryo development within and across species. RESULTS: The expression of the IGF
      mRNA varied between species in the final days of incubation in the amniotic and
      allantoic membranes. The turkey had higher (0.38-1.72 log) transcript abundance
      of IGF-I and IGF-II in the amnion and allantois compared to the chicken and duck.
      Evaluating the mRNA abundance within the chicken duodenum, jejunum, and ileum,
      the duodenum had the lowest expression of IGF-I and IGF-II (P<0.05) at day -4 of
      incubation compared to the jejunum and ileum. Focusing on differences in jejunal
      IGF expression among the three species, the turkey had the lowest IGF-I abundance
      at day -4 of incubation and highest IGF-I abundance at day of hatch (P<0.05).
      Transcript abundance of both IGF-II and IGF-R was highest in the turkey at day of
      hatch and day 1 post-hatch compared to the duck and chicken. The whole tissue
      versus the mucosal expression of the IGF mRNA abundance was evaluated during the
      post-hatch period. Duodenal, jejunal, and ileal segments had higher IGF-I
      transcript abundance (P<0.05) at day 1, day 3, and day of hatch, respectively. No
      differences were observed between segment and mucosa for IGF-II in the post-hatch
      period. The duodenal and jejunal mucosa IGF-R transcript abundance was greater
      (P<0.05) at day of hatch compared to the intestinal segment. The duck IGF mRNA in
      the jejunal mucosa was higher than the whole segment and decreased from day of
      hatch to day 3 post-hatch while the IGF mRNA abundance increased in the whole
      segment during the same time period. The turkey IGF-I transcript abundance
      decreased in both the segment and mucosa following hatch while the IGF-II mRNA
      expression increased by 1.5 logs from hatch to day 1 post-hatch. CONCLUSION: The
      transcript abundance of the IGF axis in the extra-embryonic membranes and
      gastrointestinal tissue of the developing chicken, duck, and turkey are
      influenced by embryonic age and species. A better understanding of the IGF axis
      in the small intestine during embryonic development may allow for increasing the
      optimal growth of both the gastrointestinal tract and the neonate.

PMID- 18632293
TI  - Temporal and spatial expression of IGF-I and IGFBP-1 during acute-phase response
      induced by localized inflammation in rats.
AB  - OBJECTIVE: The acute-phase response (APR), a cytokine-induced defense reaction of
      the body that enhances the innate immunity mechanisms directed to eliminate the
      noxious agent and restrict the area of damage, is accompanied by numerous
      alterations of the IGF axis. The liver is a central organ of both the IGF system
      and the APR because it releases most of IGF-I and IGFBP-1 in the circulation and
      is the main target organ for acute-phase-cytokines such as IL-6. METHODS: In the
      current work the expression of IGF-I and IGFBP-1 was studied in the liver and
      extrahepatic tissues in a rat model of localized inflammation induced by
      intramuscular injection of turpentine oil (TO). The mRNA expression of IGF-I and
      IGFBP-1 was determined by Northern blot analysis and quantitative RT-PCR.
      Circulating levels of IGF-I and IGFBP-1 were evaluated by radioimmunoassay and
      [(125)I]-IGF-I ligand blotting, respectively. RESULTS: Administration of TO to
      the rats led to a significant reduction of IGF-I gene expression in the liver and
      spleen. These changes were accompanied by a reduction of serum IGF-I
      concentrations to approximately 50% of levels observed in control rats. In
      contrast to IGF-I, IGFBP-1 mRNA expression was rapidly elevated in the livers of
      TO-treated rats. IGFBP-1 transcripts were already detectable at 30 min after TO
      injection and reached their maximal levels by 6h. IGFBP-1 gene expression was
      also increased in the kidneys. This elevation, however, was delayed and less
      prominent than in the liver. CONCLUSIONS: Our data demonstrate that localized
      inflammation induced by intramuscular TO injection is accompanied not only by
      decreased IGF-I but also by increased IGFBP-1 gene expression explaining at least
      in part the catabolic changes of metabolism observed during the acute-phase
      response.

PMID- 18632294
TI  - A new model for the anaerobic fermentation of glycerol in enteric bacteria: trunk
      and auxiliary pathways in Escherichia coli.
AB  - Anaerobic fermentation of glycerol in the Enterobacteriaceae family has long been
      considered a unique property of species that synthesize 1,3-propanediol (1,3
      PDO). However, we have discovered that Escherichia coli can ferment glycerol in a
      1,3-PDO-independent manner. We identified 1,2-propanediol (1,2-PDO) as a
      fermentation product and established the pathway that mediates its synthesis as
      well as its role in the metabolism of glycerol. We also showed that the trunk
      pathway responsible for the conversion of glycerol into glycolytic intermediates
      is composed of two enzymes: a type II glycerol dehydrogenase (glyDH-II) and a
      dihydroxyacetone kinase (DHAK), the former of previously unknown physiological
      role. Based on our findings, we propose a new model for glycerol fermentation in
      enteric bacteria in which: (i) the production of 1,2-PDO provides a means to
      consume reducing equivalents generated in the synthesis of cell mass, thus
      facilitating redox balance, and (ii) the conversion of glycerol to ethanol,
      through a redox-balanced pathway, fulfills energy requirements by generating ATP
      via substrate-level phosphorylation. The activity of the formate hydrogen-lyase
      and F(0)F(1)-ATPase systems were also found to facilitate the fermentative
      metabolism of glycerol, and along with the ethanol and 1,2-PDO pathways, were
      considered auxiliary or enabling. We demonstrated that glycerol fermentation in
      E. coli was not previously observed due to the use of medium formulations and
      culture conditions that impair the aforementioned pathways. These include high
      concentrations of potassium and phosphate, low concentrations of glycerol,
      alkaline pH, and closed cultivation systems that promote the accumulation of
      hydrogen gas.

PMID- 18632296
TI  - Factors associated with increased prevalence of human papillomavirus infection in
      a cohort of HIV-infected Brazilian women.
AB  - OBJECTIVES: Human papillomavirus (HPV) infection is a major risk factor for
      cervical disease. Using baseline data from the HIV-infected cohort of Evandro
      Chagas Clinical Research Institute at Fiocruz, Rio de Janeiro, Brazil, factors
      associated with an increased prevalence of HPV were assessed. METHODS: Samples
      from 634 HIV-infected women were tested for the presence of HPV infection using
      hybrid capture II and polymerase chain reaction. Prevalence ratios (PR) were
      estimated using Poisson regression analysis with robust variance. RESULTS: The
      overall prevalence of HPV infection was 48%, of which 94% were infected with a
      high-risk HPV. In multivariate analysis, factors independently associated with
      infection with high-risk HPV type were: younger age (<30 years of age; PR 1.5,
      95% confidence interval (CI) 1.1-2.1), current or prior drug use (PR 1.3, 95% CI
      1.0-1.6), self-reported history of HPV infection (PR 1.2, 95% CI 0.96-1.6),
      condom use in the last sexual intercourse (PR 1.3, 95% CI 1.1-1.7), and nadir
      CD4+ T-cell count <100cells/mm(3) (PR 1.6, 95% CI 1.2-2.1). CONCLUSIONS: The
      estimated prevalence of high-risk HPV-infection among HIV-infected women from Rio
      de Janeiro, Brazil, was high. Close monitoring of HPV-related effects is
      warranted in all HIV-infected women, in particular those of younger age and
      advanced immunosuppression.

PMID- 18632295
TI  - Nucleoside reverse transcriptase inhibitor resistance mutations in subtype F1
      strains isolated from heavily treated adolescents in Romania.
AB  - OBJECTIVE: To examine the nucleoside reverse transcriptase inhibitor (NRTI)
      resistance mutations in the reverse transcriptase gene of HIV-1 F1 subtype
      strains isolated from heavily treated adolescents. METHODS: Three hundred and
      fifty reverse transcriptase (RT) genotypes with at least three NRTI resistance
      mutations were included in this study; the corresponding strains were isolated
      from adolescents with a complex history of antiretroviral treatment. Subtyping
      was done using the publicly available algorithm REGA HIV-1&2. Resistance
      genotyping was performed using Big Dye Terminator chemistry provided by the
      ViroSeq genotyping system. The RT gene carrying the K65R mutation and thymidine
      analog mutations (TAMs) was cloned into pGEM-T vector (Promega), followed by
      sequencing. In order to identify mutational clusters we calculated the binomial
      (phi) correlation coefficient using SPSS 11.0 software. RESULTS: The analyzed
      sequences all belonged to the F1 subtype and were frequently carrying TAMs
      associated with substitutions at position 184. TAM-2 was the pathway more
      frequently encountered, and the demarcation between TAM-1 and TAM-2 was rather
      weak. Although the combination of K65R mutation with TAMs has rarely been
      reported because of their antagonistic effects on NRTI resistance, its presence
      was confirmed by clonal analysis of one strain. Four percent of the studied
      genotypes presented insertions and deletions in the region 67-70 of the RT gene
      and they were frequently associated with particular TAMs. Most of the NRTI
      resistance mutations were found to belong to one of three distinct clusters.
      CONCLUSION: Although the overall resistance mutations were not different from
      those described for subtype B, the subtype F1 HIV-1 NRTI mutation patterns
      displayed same specificities with possible therapeutic consequences.

PMID- 18632297
TI  - Risk factors and healing impact of multidrug-resistant bacteria in diabetic foot
      ulcers.
AB  - AIM: To determine the risk factors for acquiring multidrug-resistant organisms
      (MDRO) and their impact on outcome in infected diabetic foot ulcers. METHODS:
      Patients hospitalized in our diabetic foot unit for an episode of infected foot
      ulcer were prospectively included. Diagnosis of infection was based on clinical
      findings using the International Working Group on the Diabetic Foot-Infectious
      Diseases Society of America (IWGDF-ISDA) system, and wound specimens were
      obtained for bacterial cultures. Each patient was followed-up for 1 year.
      Univariate analysis was performed to compare infected ulcers according to the
      presence or absence of MDRO; logistic regression was used to identify explanatory
      variables for MDRO presence. Factors related to healing time were evaluated by
      univariate and multivariate survival analyses. RESULTS: MDRO were isolated in 45
      (23.9%) of the 188 patients studied. Deep and recurrent ulcer, previous
      hospitalization, HbA(1c) level, nephropathy and retinopathy were significantly
      associated with MDRO-infected ulceration. By multivariate analysis, previous
      hospitalization (OR=99.6, 95% CI=[19.9-499.0]) and proliferative retinopathy
      (OR=7.4, 95% CI=[1.6-33.7]) significantly increased the risk of MDRO infection.
      Superficial ulcers were associated with a significant decrease in healing time,
      whereas neuroischaemic ulcer, proliferative retinopathy and high HbA(1c) level
      were associated with an increased healing time. In the multivariate analysis,
      presence of MDRO had no significant influence on healing time. CONCLUSION: MDRO
      are pathogens frequently isolated from diabetic foot infection in our foot
      clinic. Nevertheless, their presence appears to have no significant impact on
      healing time if early aggressive treatment, as in the present study, is given,
      including empirical broad-spectrum antibiotic treatment, later adjusted according
      to microbiological findings.

PMID- 18632298
TI  - Study of tracheal collapsibility, compliance and stress by considering its
      asymmetric geometry.
AB  - The shape of tracheal cartilage has been widely treated as symmetric in
      analytical and numerical models. However, according to both histological images
      and in vivo medical image, tracheal cartilage is of highly asymmetric shape.
      Taking the cartilage as symmetric structure will induce bias in calculation of
      the collapse behavior, as well as compliance and muscular stress. However, this
      has been rarely discussed. In this paper, tracheal collapse is represented by
      considering its asymmetric shape. For comparison, the symmetric shape, which is
      reconstructed by half of the cartilage, is also presented. A comparison of cross
      sectional area, compliance of airway and stress in the muscular membrane,
      determined by asymmetric shape and symmetric shape is made. The result indicates
      that the symmetric assumption brings a small error, around 5% in predicting the
      cross-sectional area under loading conditions. The relative error of compliance
      is more than 10%. Particularly when the pressure is close to zero, the error
      could be more than 50%. The model considering the symmetric shape results in a
      significant difference in predicting stress in muscular membrane by either under-
      or over-estimating it. In conclusion, tracheal cartilage should not be treated as
      a symmetric structure. The results obtained in this study are helpful in
      evaluating the error induced by the assumption in geometry.

PMID- 18632299
TI  - Pulse onset detection using neighbor pulse-based signal enhancement.
AB  - Detecting onsets of cardiovascular pulse wave signals is an important
      prerequisite for successfully conducting various analysis tasks involving the
      concept of pulse wave velocity. However, pulse onsets are frequently influenced
      by inherent noise and artifacts in signals continuously acquired in a clinical
      environment. The present work proposed and validated a neighbor pulse-based
      signal enhancement algorithm for reducing error in the detected pulse onset
      locations from noise-contaminated pulsatile signals. Pulse onset was proposed to
      be detected using the first principal component extracted from three adjacent
      pulses. This algorithm was evaluated using test signals constructed by mixing
      arterial blood pressure, cerebral blood flow velocity and intracranial pressure
      pulses recorded from neurosurgical patients with white noise of various levels.
      The results showed that the proposed pulse enhancement algorithm improved
      (p<0.05) pulse onset detection according to all three different onset definitions
      and for all three types of pulsatile signals as compared to results without using
      the pulse enhancement. These results suggested that the proposed algorithm could
      help achieve robustness in pulse onset detection and facilitate pulse wave
      analysis using clinical recordings.

PMID- 18632300
TI  - Leber congenital amaurosis: genes, proteins and disease mechanisms.
AB  - Leber congenital amaurosis (LCA) is the most severe retinal dystrophy causing
      blindness or severe visual impairment before the age of 1 year. Linkage analysis,
      homozygosity mapping and candidate gene analysis facilitated the identification
      of 14 genes mutated in patients with LCA and juvenile retinal degeneration, which
      together explain approximately 70% of the cases. Several of these genes have also
      been implicated in other non-syndromic or syndromic retinal diseases, such as
      retinitis pigmentosa and Joubert syndrome, respectively. CEP290 (15%), GUCY2D
      (12%), and CRB1 (10%) are the most frequently mutated LCA genes; one intronic
      CEP290 mutation (p.Cys998X) is found in approximately 20% of all LCA patients
      from north-western Europe, although this frequency is lower in other populations.
      Despite the large degree of genetic and allelic heterogeneity, it is possible to
      identify the causative mutations in approximately 55% of LCA patients by
      employing a microarray-based, allele-specific primer extension analysis of all
      known DNA variants. The LCA genes encode proteins with a wide variety of retinal
      functions, such as photoreceptor morphogenesis (CRB1, CRX), phototransduction
      (AIPL1, GUCY2D), vitamin A cycling (LRAT, RDH12, RPE65), guanine synthesis
      (IMPDH1), and outer segment phagocytosis (MERTK). Recently, several defects were
      identified that are likely to affect intra-photoreceptor ciliary transport
      processes (CEP290, LCA5, RPGRIP1, TULP1). As the eye represents an accessible and
      immune-privileged organ, it appears to be uniquely suitable for human gene
      replacement therapy. Rodent (Crb1, Lrat, Mertk, Rpe65, Rpgrip1), avian (Gucy2D)
      and canine (Rpe65) models for LCA and profound visual impairment have been
      successfully corrected employing adeno-associated virus or lentivirus-based gene
      therapy. Moreover, phase 1 clinical trials have been carried out in humans with
      RPE65 deficiencies. Apart from ethical considerations inherently linked to
      treating children, major obstacles for the treatment of LCA could be the putative
      developmental deficiencies in the visual cortex in persons blind from birth
      (amblyopia), the absence of sufficient numbers of viable photoreceptor or RPE
      cells in LCA patients, and the unknown and possibly toxic effects of
      overexpression of transduced genes. Future LCA research will focus on the
      identification of the remaining causal genes, the elucidation of the molecular
      mechanisms of disease in the retina, and the development of gene therapy
      approaches for different genetic subtypes of LCA.

PMID- 18632301
TI  - Prefrontal cortex volume reduction on MRI in preclinical Huntington's disease
      relates to visuomotor performance and CAG number.
AB  - PURPOSE: To investigate grey matter volumes on magnetic resonance imaging (MRI)
      in preclinical Huntington's disease (HD), and their relationship to
      neuropsychology and CAG number. MATERIAL AND METHODS: Twenty preclinical HD
      carriers and 21 healthy controls matched for age, sex, and educational level were
      included in this study. Clinical (UHDRS), and detailed neuropsychological
      assessments, and 3D IR SPGR axial MR acquisition. Calculation of global,
      segmented (SIENAX), and focal (voxel based morphometry, VBM) grey matter volumes
      was carried out. An analysis of variance (ANOVA) and a general linear model for
      VBM analysis were used to compare preclinical HD carriers and controls. Small
      volume correction was used, and clusters at p<0.05 were considered significant.
      Correlation analysis (VBM) with neuropsychology, and CAG number was also
      performed. RESULTS: Preclinical HD carriers showed, compared to controls, smaller
      global volumes of the brain (1279+/-6 vs. 1331+/-46, p=0.003), total (666+/-48
      vs. 698+/-34, p=0.020) and cortical grey matter (551+/-44 vs. 577+/-32, p=0.035).
      When compared to the controls, preclinical carriers showed focal volume losses,
      which were more prominent in the left prefrontal cortex, cerebellum, and right
      posterior temporal cortex. Preclinical HD performed slower in a visuomotor
      integration task, the 15-Objects test, than controls (t (1,25.02)=3.69; p=0.001:
      pre-HD: 69.55+/-28.86; controls: 45.79+/-8.38). A correlation was found between
      volume loss in the prefrontal cortex, visuomotor performance, and CAG number.
      CONCLUSION: Preclinical HD carriers show grey matter volume reduction involving
      the prefrontal cortex, which relates to the visuomotor performance and CAG
      number. This suggests that regionally selective neuronal loss/dysfunction occurs
      prior to the clinical onset of symptoms.

PMID- 18632302
TI  - HIV/AIDS-related stigma in Kumasi, Ghana.
AB  - OBJECTIVE: To assess HIV/AIDS-related stigma and discrimination of people living
      with HIV/AIDS (PLWHA) in Kumasi, Ghana. METHODS: A cross-sectional survey of 104
      adults from the four sub-districts in Kumasi was conducted. RESULTS: Four stigma
      constructs, employment-based discrimination, screening and identification of HIV
      positive people, revelation of HIV status and social contact stigma were
      determined based on reliability measures from responses to the questionnaire.
      Regression analysis showed that participants with higher educational attainment
      were more likely to favor policies denying employment to PLWHA (p<0.05), but
      disapproved of revealing HIV sero-status (p<0.05). Muslims were more likely than
      Christians to agree with identifying PLWHA (p<0.05) and more likely to advocate
      revealing HIV sero-status (p<0.05). Males were more likely to favor revealing HIV
      status (p<0.05). Employed persons were more likely to have social contact with
      PLWHA (p<0.05). CONCLUSIONS: These findings are useful in guiding the design of
      interventions against HIV/AIDS-related stigma in Kumasi.

PMID- 18632303
TI  - Plants to power: bioenergy to fuel the future.
AB  - Bioenergy should play an essential part in reaching targets to replace petroleum
      based transportation fuels with a viable alternative, and in reducing long-term
      carbon dioxide emissions, if environmental and economic sustainability are
      considered carefully. Here, we review different platforms, crops, and
      biotechnology-based improvements for sustainable bioenergy. Among the different
      platforms, there are two obvious advantages to using lignocellulosic biomass for
      ethanol production: higher net energy gain and lower production costs. However,
      the use of lignocellulosic ethanol as a viable alternative to petroleum-based
      transportation fuels largely depends on plant biotechnology breakthroughs. We
      examine how biotechnology, such as lignin modification, abiotic stress
      resistance, nutrition usage, in planta expression of cell wall digestion enzymes,
      biomass production, feedstock establishment, biocontainment of transgenes,
      metabolic engineering, and basic research, can be used to address the challenges
      faced by bioenergy crop production.

PMID- 18632304
TI  - A method to estimate the spatial extent of activation in thalamic deep brain
      stimulation.
AB  - OBJECTIVE: The goal of this study was to develop, evaluate, and apply a method to
      quantify the unknown spatial extent of activation in deep brain stimulation (DBS)
      of the ventral intermedius nucleus (Vim) of the thalamus. METHODS: The amplitude
      distance relationship and the threshold amplitudes to elicit clinical responses
      were combined to estimate the unknown amplitude-distance constant and the
      distance between the electrode and the border between the Vim and the
      ventrocaudal nucleus (Vc) of the thalamus. We tested the sensitivity of the
      method to errors in the input parameters, and subsequently applied the method to
      estimate the amplitude-distance constant from clinically-measured threshold
      amplitudes. RESULTS: The method enabled estimation of the amplitude-distance
      constant with a median squared error of 0.07-0.23V/mm2 and provided an estimate
      of the distance between the electrode and the Vc/Vim border with a median squared
      error of 0.01-0.04mm. Application of the method to clinically-measured threshold
      amplitudes to elicit paresthesias estimated the amplitude-distance constant to be
      0.22V/mm2. CONCLUSIONS: The method enabled robust quantification of the spatial
      extent of activation in thalamic DBS and predicted that stimulation amplitudes of
      1-3.5V would produce a mean effective radius of activation of 2.0-3.9mm.
      SIGNIFICANCE: Knowing the spatial extent of activation may improve methods of
      electrode placement and stimulation parameter selection in DBS.

PMID- 18632305
TI  - Ten Hertz thalamus stimulation increases tremor activity in the subthalamic
      nucleus in a patient with Parkinson's disease.
AB  - OBJECTIVE: In patients with Parkinson's disease (PD) the effect of thalamic
      stimulation on tremor pathophysiology remains largely unclear. By recording local
      field potentials (LFPs) in the subthalamic nucleus (STN) while stimulating the
      nucleus ventralis intermedius thalami (VIM), information of the stimulation
      effects should be gained. METHODS: We had the unique opportunity to
      intraoperatively record LFPs of the STN in a patient with PD while stimulating
      the VIM. VIM electrodes had been implanted 9 years previously because of tremor.
      Due to worsening of clinical symptoms an implantation of STN electrodes had
      become necessary. RESULTS: High frequency stimulation in the VIM lowered the
      power of the tremor frequency band (4-7Hz) in the STN. In contrast, 10Hz VIM
      stimulation elevated the power of the tremor frequency band as well as STN-EMG
      coupling. CONCLUSIONS: The effect of high frequency stimulation may explain the
      improvement of tremor in patients who are treated with VIM deep brain
      stimulation. The power elevation during 10Hz stimulation suggests that the
      pathological cerebral and cerebral-muscular communication in PD is mainly driven
      at 10Hz. SIGNIFICANCE: The direct cerebral recordings support the view that a
      10Hz network is a pathophysiological key mechanism in the generation of motor
      deficits in PD.

PMID- 18632306
TI  - The clinical utility of methods to determine spatial extent and volume of tissue
      activated by deep brain stimulation.

PMID- 18632308
TI  - Only half of the chronic pain after thoracic surgery shows a neuropathic
      component.
AB  - Chronic pain is a common complication after thoracic surgery. The cause of
      chronic post-thoracotomy pain is often suggested to be intercostal nerve damage.
      Thus chronic pain after thoracic surgery should have an important neuropathic
      component. The present study investigated the prevalence of the neuropathic
      component in chronic pain after thoracic surgery. Furthermore, we looked for
      predictive factors for prevalence and intensity of chronic pain. We contacted 243
      patients who underwent a video-assisted thoracoscopy (VATS) or thoracotomy in the
      period between January 2004 and September 2006 by mail. Patients retrospectively
      received a questionnaire with the Dutch version of the PainDETECT Questionnaire,
      a validated screening tool for neuropathic pain. Results were analyzed from 204
      patients (144 thoracotomies, 60 VATS). The prevalence of chronic pain was 40%
      after thoracotomy and 47% after VATS. Definite chronic neuropathic pain was
      present in 23% of the patients with chronic pain, with an additional 30% having
      probable neuropathic pain. Greater probability of neuropathic pain (ie, a higher
      total score of the PainDETECT) correlated with more intense chronic pain.
      Predictive factors for chronic pain were younger age (P = .01), radiotherapy (P =
      .043), pleurectomy (P = .04) and more extensive surgery (P < .001). PERSPECTIVE:
      Up to half the chronic pain after thoracic surgery is not associated with a
      neuropathic component, which has not been reported to date. More extensive
      surgery and pleurectomy are predictive factors for chronic pain after thoracic
      surgery, suggesting a visceral component apart from nerve injury.

PMID- 18632307
TI  - Footshock-induced urinary bladder hypersensitivity: role of spinal corticotropin
      releasing factor receptors.
AB  - Stress-induced hyperalgesia (SIH), a common clinical observation associated with
      multiple painful diseases including functional urinary disorders, presently has
      no mechanistic explanation. Using a footshock treatment, a classic stressor, to
      magnify physiological responses in a model of urinary bladder pain, we examined
      one potential group of mediators of SIH, the corticotropin-releasing factor (CRF)
      related neuropeptides. Exposure to a footshock treatment produced bladder
      hypersensitivity in female Sprague-Dawley rats, manifested as significantly more
      vigorous visceromotor responses (VMRs) to urinary bladder distension (UBD)
      compared with rats that were exposed to a non-footshock treatment. This bladder
      hypersensitivity was significantly attenuated by blocking spinal CRF(2) receptors
      but not CRF(1) receptors. Furthermore, spinal administration of urocortin 2, a
      CRF(2) receptor agonist, augmented UBD-evoked VMRs in a way similar to what was
      observed after exposure to Footshock, an effect significantly attenuated by
      pretreatment with spinal aSVG30, a CRF(2) receptor antagonist. Surprisingly,
      neither spinal administration of CRF nor the CRF(1) receptor antagonist
      antalarmin had an effect on bladder nociceptive responses. The results of the
      present study not only provide further support for a role of stress in the
      exacerbation of bladder pain but also implicate spinal urocortins and their
      endogenous receptor, the CRF(2) receptor, as potential mediators of this effect.
      PERSPECTIVE: This study presents evidence that spinal urocortins and CRF(2)
      receptors are involved in stress-induced hypersensitivity related to the urinary
      bladder. This provides a basis for investigating how urocortins mediate SIH,
      ultimately leading to more effective treatment options for patients with painful
      bladder syndromes as well as stress-exacerbated chronic pain.

PMID- 18632309
TI  - Validation of the Chronic Pain Acceptance Questionnaire (CPAQ) in Cantonese
      speaking Chinese patients.
AB  - Acceptance of chronic pain has become an important concept in understanding and
      predicting that chronic pain sufferers can remain engaged with meaningful aspects
      of life. Assessment of acceptance has been facilitated by the development of
      Chronic Pain Acceptance Questionnaire (CPAQ). In this study, we aimed to test the
      reliability and validity of translated Chinese version of CPAQ to use this
      important tool in the future management of Hong Kong Chinese patients with
      chronic nonmalignant pain. Content validity was established by consensus formed
      among a panel of 5 experts in clinical psychology and pain specialty during the
      process of forward and backward translations. Test-retest reliability was
      examined by completing the Chinese CPAQ twice, 2 weeks apart, by 54 patients. A
      total of 224 Chinese patients with chronic nonmalignant pain attending our
      cluster multidisciplinary pain clinic were asked to complete a battery of
      psychometric instruments in Chinese, including an intake form for demographic
      data, Hospital Anxiety and Depression Score (HADS), Medical Outcome Study Short
      Form 36 (SF-36), Pain Catastrophizing Scale (PCS), and Pain Self-Efficacy
      Questionnaire (PSEQ). Analysis results showed that Chinese CPAQ had good test
      retest reliability (intraclass correlation coefficient, 0.79) and internal
      consistency reliability (Cronbach alpha = 0.79). The Chinese CPAQ score was
      significantly correlated to anxiety, depression, pain catastrophizing, pain self
      efficacy, and physical and psychosocial disability. Scree plot and Principal
      Components Factor analysis confirmed the same 2-factor construct as the original
      English CPAQ. Construct validity of the Chinese CPAQ can therefore be supported.
      In conclusion, the Chinese CPAQ is a reliable clinical assessment tool with valid
      construct for acceptance measurement in our heterogeneous Chinese patients sample
      with chronic nonmalignant pain. PERSPECTIVE: This article confirms the
      reliability and validity of a Chinese version of the CPAQ. The Chinese CPAQ can
      then be used by pain clinicians caring for Chinese chronic pain patients
      worldwide for acceptance-based psychometric assessment as well as therapies.

PMID- 18632310
TI  - Heart rate variability predicts anti-tumor necrosis factor therapy response for
      inflammatory arthritis.
AB  - To consider autonomic status as a predictor of anti-tumor necrosis factor (TNF)
      treatment response for inflammatory arthritis, we conducted an exploratory,
      double-blind, 52-week study with 33 patients with rheumatoid (25) or psoriatic
      (8) arthritis using heart rate variability (HRV). All were assessed for
      parasympathetic, sympathetic, total power and tension index measures of autonomic
      reactivity at initiation of anti-TNF therapy with etanercept (15) or adalimumab
      (18). Clinical response was assessed at 6, 12, 26 and 52 weeks by internationally
      accepted outcome criteria (ACR20/50/70 and DAS28 response). Predictive value was
      demonstrated for all HRV assessments (p-value range 0.001-0.032), except
      sympathetic (p-value range 0.06-0.22), for ACR20, ACR50 and ACR70 at 52 weeks and
      at as early as 6 weeks for some measures. Only parasympathetic and tension index
      predicted DAS28 outcome (p-value range 0.009-0.024). Poor anti-TNF response was
      associated with low parasympathetic, low total power, high sympathetic and high
      tension index measures, a profile also predominant in the prior anti-TNF failure
      subset (12). In conclusion, this unique, exploratory study suggests that HRV may
      be a novel, useful predictor of response to anti-TNF therapy in patients with
      inflammatory arthritis, and emphasizes the importance of autonomic influence of
      autoimmune disease expression.

PMID- 18632311
TI  - Direct electrochemical study of the multiple redox centers of hydrogenase from
      Desulfovibrio gigas.
AB  - Direct electrochemical response was first time observed for the redox centers of
      Desulfovibrio gigas [NiFe]-Hase, in non-turnover conditions, by cyclic
      voltammetry, in solution at glassy carbon electrode. The activation of the enzyme
      was achieved by reduction with H(2) and by electrochemical control and
      electrocatalytic activity was observed. The inactivation of the [NiFe]-Hase was
      also attained through potential control. All electrochemical data was obtained in
      the absence of enzyme inhibitors. The results are discussed in the context of the
      proposed mechanism currently accepted for activation/inactivation of [NiFe]
      Hases.

PMID- 18632312
TI  - Intestinal lipid transport and chylomicron production: possible links to
      exacerbated atherogenesis in a rodent model of the metabolic syndrome.
AB  - Post-prandial lipaemia is prevalent during conditions of obesity and insulin
      resistance (IR), and has been associated with mediating the accelerated
      progression of cardiovascular disease (CVD). Our group has contributed to the
      concept that intestinally derived chylomicron lipoproteins are atherogenic and
      are associated with increased cholesterol accumulation in arterial vessels. More
      recently we have established the JCR:LA-cp rodent model of post-prandial
      dyslipidemia during conditions of the metabolic syndrome (MetS): including
      obesity, insulin-resistance and intimal atherogenesis. We have used this model as
      a novel physiological approach to investigate intestinal lipid transport and
      metabolism in the 'absorption-to-chylomicron secretion' axis, in the context of
      IR. The purpose of this review is to highlight recent preliminary data that has
      been collected using a range of different methodologies in this unique model of
      MetS. For the first time we report that the JCR:LA-cp rodent has over-production
      of intestinal chylomicrons and that this is associated with intestinal villus
      hypertrophy. We have also observed that vascular re-modelling associated with
      increased arterial accumulation of atherogenic lipoproteins is evident in this
      model. We discuss our findings in the context of a void of knowledge in the
      understanding of intestinal lipid metabolism, and the potential significance of
      these pathways in contributing to dyslipidemia in MetS.

PMID- 18632315
TI  - Risk factors for the gastric cancer: a case-control study in Tibet.

PMID- 18632314
TI  - Liquid chromatography-tandem mass spectrometric quantification of the dehydration
      product of tetranor PGE-M, the major urinary metabolite of prostaglandin E(2) in
      human urine.
AB  - A LC-MS/MS method has been developed to analyze tetranor PGE-M, the major urinary
      metabolite of PGE(2), that involves the acid-catalyzed dehydration of tetranor
      PGE-M and its deuterated (d(6)) analog followed by LC-MS/MS measurement of the
      dehydrated tetranor PGE-M product (tetranor PGA-M). We also report a method for
      quantification of creatinine in urine by LC-MS/MS to normalize tetranor PGE-M
      concentrations with that of urinary creatinine. These methods were used to study
      the effect of aspirin on urinary tetranor PGE-M levels in healthy male
      volunteers. Aspirin did not affect urinary creatinine concentrations but
      decreased urinary tetranor PGE-M concentrations by approximately 44%.

PMID- 18632313
TI  - The biophysical function of pulmonary surfactant.
AB  - Pulmonary surfactant lowers surface tension in the lungs. Physiological studies
      indicate two key aspects of this function: that the surfactant film forms
      rapidly; and that when compressed by the shrinking alveolar area during
      exhalation, the film reduces surface tension to very low values. These
      observations suggest that surfactant vesicles adsorb quickly, and that during
      compression, the adsorbed film resists the tendency to collapse from the
      interface to form a 3D bulk phase. Available evidence suggests that adsorption
      occurs by way of a rate-limiting structure that bridges the gap between the
      vesicle and the interface, and that the adsorbed film avoids collapse by
      undergoing a process of solidification. Current models, although incomplete,
      suggest mechanisms that would partially explain both rapid adsorption and
      resistance to collapse as well as how different constituents of pulmonary
      surfactant might affect its behavior.

PMID- 18632316
TI  - Complete salvage of impending free flap failure in heparin induced
      thrombocytopenia by emergent institution of therapy with argatroban.

PMID- 18632317
TI  - Leakage and osmotic shifts in PIP Hydrogel implants. A case demonstrating
      increase and decrease of implant volume in the same patient.

PMID- 18632318
TI  - Permanent scarring in a partial thickness scald burn dressed with Biobrane.
AB  - Biobrane is a biosynthetic wound dressing which has shown to be effective in
      partial thickness burns by improving wound healing, reducing the pain in dressing
      changes, and the need to use skin grafts. In addition, it has been shown to
      reduce both in-patient and outpatient hospital costs and incur no increase in
      infection rates. Recently, the first reported case of punctate scarring from the
      use of Biobrane in a paediatric scald was published [Hassan Z, Shah M. Punctate
      scarring from use of porous Biobrane. Burns 2006;32:258-60]. We now report a
      second case of scarring with Biobrane, in which the Biobrane was left in place
      for a full 14 days, as recommended by the manufacturers.

PMID- 18632320
TI  - Mobile graphics.
AB  - Mobile phones form a ubiquitous graphics platform; over half of the world
      population uses them. This special issue presents solutions that overcome some of
      the inherent limitations of these compact computing devices and make use of the
      fact that they are available at all times, not just at your desk.

PMID- 18632321
TI  - Gait analysis using a shoe-integrated wireless sensor system.
AB  - We describe a wireless wearable system that was developed to provide quantitative
      gait analysis outside the confines of the traditional motion laboratory. The
      sensor suite includes three orthogonal accelerometers, three orthogonal
      gyroscopes, four force sensors, two bidirectional bend sensors, two dynamic
      pressure sensors, as well as electric field height sensors. The "GaitShoe" was
      built to be worn in any shoe, without interfering with gait and was designed to
      collect data unobtrusively, in any environment, and over long periods. The
      calibrated sensor outputs were analyzed and validated with results obtained
      simultaneously from the Massachusetts General Hospital, Biomotion Laboratory. The
      GaitShoe proved highly capable of detecting heel-strike and toe-off, as well as
      estimating foot orientation and position, inter alia.

PMID- 18632322
TI  - X-PAT: a multiplatform patient referral data management system for small
      healthcare institution requirements.
AB  - We present X-PAT, a platform-independent software prototype that is able to
      manage patient referral multimedia data in an intranet network scenario according
      to the specific control procedures of a healthcare institution. It is a self
      developed storage framework based on a file system, implemented in eXtensible
      Markup Language (XML) and PHP Hypertext Preprocessor Language, and addressed to
      the requirements of limited-dimension healthcare entities (small hospitals,
      private medical centers, outpatient clinics, and laboratories). In X-PAT,
      healthcare data descriptions, stored in a novel Referral Base Management System
      (RBMS) according to Health Level 7 Clinical Document Architecture Release 2 (CDA
      R2) standard, can be easily applied to the specific data and organizational
      procedures of a particular healthcare working environment thanks also to the use
      of standard clinical terminology. Managed data, centralized on a server, are
      structured in the RBMS schema using a flexible patient record and CDA healthcare
      referral document structures based on XML technology. A novel search engine
      allows defining and performing queries on stored data, whose rapid execution is
      ensured by expandable RBMS indexing structures. Healthcare personnel can
      interface the X-PAT system, according to applied state-of-the-art privacy and
      security measures, through friendly and intuitive Web pages that facilitate user
      acceptance.

PMID- 18632323
TI  - Optimal electrocardiographic lead systems: practical scenarios in smart clothing
      and wearable health systems.
AB  - Advances in wearable health systems, from a smart textile, signal processing, and
      wireless communications perspective, have resulted in the recent deployment of
      such systems in real clinical and healthcare settings. Nevertheless, the problem
      of identifying the most appropriate sites from which biological parameters can be
      recorded still remains unsolved. This paper aims to asses the effects of various
      practical constraints that may be encountered when choosing electrocardiographic
      recording sites for wearable health systems falling within the category of smart
      shirts for cardiac monitoring and analysis. We apply a lead selection algorithm
      to a set of 192 lead body surface potential maps (BSPM) and simulate a number of
      practical constraints by only allowing selection of recording sites from specific
      regions available in the 192 lead array. Of the various scenarios that were
      investigated, we achieved the best results when the selection process to identify
      the recording sites was constrained to an area around the precordial region. The
      top ten recording sites chosen in this region exhibited an rms voltage error of
      25.8 mu V when they were used to estimate total ECG information. The poorest
      performing scenario was that which constrained the selection to two vertical
      strips on the posterior surface. The top ten recording sites chosen in this
      scenario exhibited an rms voltage error of 41.1 muV. In general, it was observed
      that out of all the scenarios investigated, those which constrained available
      regions to the posterior and lateral surfaces performed less favorably than those
      where electrodes could also be chosen on the anterior surface. The overall
      results from our approach have validated the proposed algorithm and its ability
      to select optimal recording sites taking into consideration the practical
      constraints that may exist with smart shirts.

PMID- 18632324
TI  - Efficient lossless compression of 4-D medical images based on the advanced video
      coding scheme.
AB  - This paper presents an efficient lossless compression method for 4-D medical
      images based on the advanced video coding scheme (H.264/AVC). The proposed method
      efficiently reduces data redundancies in all four dimensions by recursively
      applying multiframe motion compensation. Performance evaluations on real 4-D
      medical images of varying modalities including functional magnetic resonance show
      an improvement in compression efficiency of up to three times that of other state
      of-the-art compression methods such as 3D-JPEG2000.

PMID- 18632325
TI  - Automated diagnosis of coronary artery disease based on data mining and fuzzy
      modeling.
AB  - A fuzzy rule-based decision support system (DSS) is presented for the diagnosis
      of coronary artery disease (CAD). The system is automatically generated from an
      initial annotated dataset, using a four stage methodology: 1) induction of a
      decision tree from the data; 2) extraction of a set of rules from the decision
      tree, in disjunctive normal form and formulation of a crisp model; 3)
      transformation of the crisp set of rules into a fuzzy model; and 4) optimization
      of the parameters of the fuzzy model. The dataset used for the DSS generation and
      evaluation consists of 199 subjects, each one characterized by 19 features,
      including demographic and history data, as well as laboratory examinations.
      Tenfold cross validation is employed, and the average sensitivity and specificity
      obtained is 62% and 54%, respectively, using the set of rules extracted from the
      decision tree (first and second stages), while the average sensitivity and
      specificity increase to 80% and 65%, respectively, when the fuzzification and
      optimization stages are used. The system offers several advantages since it is
      automatically generated, it provides CAD diagnosis based on easily and
      noninvasively acquired features, and is able to provide interpretation for the
      decisions made.

PMID- 18632326
TI  - Improving pattern discovery and visualization of SAGE data through poisson-based
      self-adaptive neural networks.
AB  - Serial analysis of gene expression (SAGE) allows a detailed, simultaneous
      analysis of thousands of genes without the need for prior, complete gene sequence
      information. However, due to its inherent complexity and the lack of complete
      structural and function knowledge, mining vast collections of SAGE data to
      extract useful knowledge poses great challenges to traditional analytical
      techniques. Moreover, SAGE data are characterized by a specific statistical model
      that has not been incorporated into traditional data analysis techniques. The
      analysis of SAGE data requires advanced, intelligent computational techniques,
      which consider the underlying biology and the statistical nature of SAGE data. By
      addressing the statistical properties demonstrated by SAGE data, this paper
      presents a new self-adaptive neural network, Poisson-based growing self
      organizing map (PGSOM), which implements novel weight adaptation and neuron
      growing strategies. An empirical study of key dynamic mechanisms of PGSOM is
      presented. It was tested on three datasets, including synthetic and experimental
      SAGE data. The results indicate that, in comparison to traditional techniques,
      the PGSOM offers significant advantages in the context of pattern discovery and
      visualization in SAGE data. The pattern discovery and visualization platform
      discussed in this paper can be applied to other problem domains where the data
      are better approximated by a Poisson distribution.

PMID- 18632327
TI  - The INCA system: a further step towards a telemedical artificial pancreas.
AB  - Biomedical engineering research efforts have accomplished another level of a
      "technological solution" for diabetes: an artificial pancreas to be used by
      patients and supervised by healthcare professionals at any time and place.
      Reliability of continuous glucose monitoring, availability of real-time
      programmable insulin pumps, and validation of safe and efficient control
      algorithms are critical components for achieving that goal. Nevertheless, the
      development and integration of these new technologies within a telemedicine
      system can be the basis of a future artificial pancreas. This paper introduces
      the concept, design, and evaluation of the "intelligent control assistant for
      diabetes, INCA" system. INCA is a personal digital assistant (PDA)-based personal
      smart assistant to provide patients with closed-loop control strategies (personal
      and remote loop), based on a real-time continuous glucose sensor (Guardian RT,
      Medtronic), an insulin pump (D-TRON, Disetronic Medical Systems), and a mobile
      general packet radio service (GPRS)-based telemedicine communication system.
      Patient therapeutic decision making is supervised by doctors through a
      multiaccess telemedicine central server that provides to diabetics and doctors a
      Web-based access to continuous glucose monitoring and insulin infusion data. The
      INCA system has been technically and clinically evaluated in two randomized and
      crossover clinical trials showing an improvement on glycaemic control of diabetic
      patients.

PMID- 18632328
TI  - Automated retinal image analysis over the internet.
AB  - Retinal clinicians and researchers make extensive use of images, and the current
      emphasis is on digital imaging of the retinal fundus. The goal of this paper is
      to introduce a system, known as retinal image vessel extraction and registration
      system, which provides the community of retinal clinicians, researchers, and
      study directors an integrated suite of advanced digital retinal image analysis
      tools over the Internet. The capabilities include vasculature tracing and
      morphometry, joint (simultaneous) montaging of multiple retinal fields, cross
      modality registration (color/red-free fundus photographs and fluorescein
      angiograms), and generation of flicker animations for visualization of changes
      from longitudinal image sequences. Each capability has been carefully validated
      in our previous research work. The integrated Internet-based system can enable
      significant advances in retina-related clinical diagnosis, visualization of the
      complete fundus at full resolution from multiple low-angle views, analysis of
      longitudinal changes, research on the retinal vasculature, and objective,
      quantitative computer-assisted scoring of clinical trials imagery. It could pave
      the way for future screening services from optometry facilities.

PMID- 18632329
TI  - Mining unexpected temporal associations: applications in detecting adverse drug
      reactions.
AB  - In various real-world applications, it is very useful mining unanticipated
      episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking
      two medicines together sometimes causing an adverse reaction. These unanticipated
      episodes are usually unexpected and infrequent, which makes existing data mining
      techniques, mainly designed to find frequent patterns, ineffective. In this
      paper, we propose unexpected temporal association rules (UTARs) to describe them.
      To handle the unexpectedness, we introduce a new interestingness measure,
      residual-leverage, and develop a novel case-based exclusion technique for its
      calculation. Combining it with an event-oriented data preparation technique to
      handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs.
      The MUTARC is applied to generate adverse drug reaction (ADR) signals from real
      world healthcare administrative databases. It reliably shortlists not only six
      known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis,
      which our algorithm designers and experiment runners have not known before the
      experiments. The MUTARC performs much more effectively than existing techniques.
      This paper clearly illustrates the great potential along the new direction of ADR
      signal generation from healthcare administrative databases.

PMID- 18632330
TI  - Mobile diary for wellness management--results on usage and usability in two user
      studies.
AB  - The prevalence of lifestyle-related health problems is increasing rapidly. Many
      of the diseases and health risks could be prevented or alleviated by making
      changes toward healthier lifestyles. We have developed the Wellness Diary (WD), a
      concept for personal and mobile wellness management based on Cognitive-Behavioral
      Therapy (CBT). Two implementations of the concept were made for the Symbian
      Series 60 (S60) mobile phone platform, and their usability, usage, and acceptance
      were studied in two 3-month user studies. Study I was related to weight
      management and study II to general wellness management. In both the studies, the
      concept and its implementations were well accepted and considered as easy to use
      and useful in wellness management. The usage rate of the WD was high and
      sustained at a high level throughout the study. The average number of entries
      made per day was 5.32 (SD = 2.59, range = 0-14) in study I, and 5.48 (SD = 2.60,
      range = 0-17) in study II. The results indicate that the WD is well suited for
      supporting CBT-based wellness management.

PMID- 18632331
TI  - The model repository of the models of infectious disease agent study.
AB  - The model repository (MREP) is a relational database management system (RDBMS)
      developed under the auspices of models of infectious disease agent study (MIDAS).
      The purpose of the MREP is to organize and catalog the models, results, and
      suggestions for using the MIDAS and to store them in a way to allow users to run
      models from an access-controlled disease MREP. The MREP contains source and
      object code of disease models developed by infectious disease modelers and tested
      in a production environment. Different versions of models used to describe
      various aspects of the same disease are housed in the repository. Models are
      linked to their developers and different versions of the codes are tied to
      Subversion, a version control tool. An additional element of the MREP will be to
      house, manage, and control access to a disease model results warehouse, which
      consists of output generated by the models contained in the MREP. The result
      tables and files are linked to the version of the model and the input parameters
      that collectively generated the results. The result tables are warehoused in a
      relational database that permits them to be easily identified, categorized, and
      downloaded.

PMID- 18632332
TI  - Helicobacter pylori-related gastric histology classification using support-vector
      machine-based feature selection.
AB  - This study presents a computer-aided diagnosis system using sequential forward
      floating selection (SFFS) with support vector machine (SVM) to diagnose gastric
      histology of Helicobacter pylori (H. pylori) from endoscopic images. To achieve
      this goal, candidate image features associated with clinical symptoms are
      extracted from endoscopic images. With these candidate features, the SFFS method
      is applied to select feature subsets, which perform the best classification
      results under SVM with respect to different histological features. By using the
      classifiers obtained from the feature subsets, a new diagnosis system is
      implemented to provide physicians with H. pylori -related histological results
      from endoscopic images.

PMID- 18632333
TI  - Detection of infarct lesions from single MRI modality using inconsistency between
      voxel intensity and spatial location--a 3-D automatic approach.
AB  - Detection of infarct lesions using traditional segmentation methods is always
      problematic due to intensity similarity between lesions and normal tissues, so
      that multispectral MRI modalities were often employed for this purpose. However,
      the high costs of MRI scan and the severity of patient conditions restrict the
      collection of multiple images. Therefore, in this paper, a new 3-D automatic
      lesion detection approach was proposed, which required only a single type of
      anatomical MRI scan. It was developed on a theory that, when lesions were
      present, the voxel-intensity-based segmentation and the spatial-location-based
      tissue distribution should be inconsistent in the regions of lesions. The degree
      of this inconsistency was calculated, which indicated the likelihood of tissue
      abnormality. Lesions were identified when the inconsistency exceeded a defined
      threshold. In this approach, the intensity-based segmentation was implemented by
      the conventional fuzzy c-mean (FCM) algorithm, while the spatial location of
      tissues was provided by prior tissue probability maps. The use of simulated MRI
      lesions allowed us to quantitatively evaluate the performance of the proposed
      method, as the size and location of lesions were prespecified. The results showed
      that our method effectively detected lesions with 40-80% signal reduction
      compared to normal tissues (similarity index > 0.7). The capability of the
      proposed method in practice was also demonstrated on real infarct lesions from 15
      stroke patients, where the lesions detected were in broad agreement with true
      lesions. Furthermore, a comparison to a statistical segmentation approach
      presented in the literature suggested that our 3-D lesion detection approach was
      more reliable. Future work will focus on adapting the current method to multiple
      sclerosis lesion detection.

PMID- 18632334
TI  - A novel and efficient technique for identification and classification of GPCRs.
AB  - G-protein coupled receptors (GPCRs) play a vital role in different biological
      processes, such as regulation of growth, death, and metabolism of cells. GPCRs
      are the focus of significant amount of current pharmaceutical research since they
      interact with more than 50% of prescription drugs. The dipeptide-based support
      vector machine (SVM) approach is the most accurate technique to identify and
      classify the GPCRs. However, this approach has two major disadvantages. First,
      the dimension of dipeptide-based feature vector is equal to 400. The large
      dimension makes the classification task computationally and memory wise
      inefficient. Second, it does not consider the biological properties of protein
      sequence for identification and classification of GPCRs. In this paper, we
      present a novel-feature-based SVM classification technique. The novel features
      are derived by applying wavelet-based time series analysis approach on protein
      sequences. The proposed feature space summarizes the variance information of
      seven important biological properties of amino acids in a protein sequence. In
      addition, the dimension of the feature vector for proposed technique is equal to
      35. Experiments were performed on GPCRs protein sequences available at GPCRs
      Database. Our approach achieves an accuracy of 99.9%, 98.06%, 97.78%, and 94.08%
      for GPCR superfamily, families, subfamilies, and subsubfamilies (amine group),
      respectively, when evaluated using fivefold cross-validation. Further, an
      accuracy of 99.8%, 97.26%, and 97.84% was obtained when evaluated on unseen or
      recall datasets of GPCR superfamily, families, and subfamilies, respectively.
      Comparison with dipeptide-based SVM technique shows the effectiveness of our
      approach.

PMID- 18632335
TI  - Globally convergent algorithms for estimating generalized gamma distributions in
      fast signal and image processing.
AB  - Many applications in real-time signal, image, and video processing require
      automatic algorithms for rapid characterizations of signals and images through
      fast estimation of their underlying statistical distributions. We present fast
      and globally convergent algorithms for estimating the three-parameter generalized
      gamma distribution (G Gamma D). The proposed method is based on novel scale
      independent shape estimation (SISE) equations. We show that the SISE equations
      have a unique global root in their semi-infinite domains and the probability that
      the sample SISE equations have a unique global root tends to one. The consistency
      of the global root, its scale, and index shape estimators is obtained.
      Furthermore, we establish that, with probability tending to one, Newton-Raphson
      (NR) algorithms for solving the sample SISE equations converge globally to the
      unique root from any initial value in its given domain. In contrast to existing
      methods, another remarkable novelty is that the sample SISE equations are
      completely independent of gamma and polygamma functions and involve only
      elementary mathematical operations, making the algorithms well suited for real
      time both hardware and software implementations. The SISE estimators also allow
      the maximum likelihood (ML) ratio procedure to be carried out for testing the
      generalized Gaussian distribution (GGD) versus the G Gamma D. Finally, the fast
      global convergence and accuracy of our algorithms for finite samples are
      demonstrated by both simulation studies and real image analysis.

PMID- 18632336
TI  - Local hull-based surface construction of volumetric data from silhouettes.
AB  - The marching cubes (MC) is a general method which can construct a surface of an
      object from its volumetric data generated using a shape from silhouette method.
      Although MC is efficient and straightforward to implement, a MC surface may have
      discontinuity even though the volumetric data is continuous. This is because
      surface construction is more sensitive to image noise than the construction of
      volumetric data. To address this problem, we propose a surface construction
      algorithm which aggregates local surfaces constructed by the 3-D convex hull
      algorithm. Thus, the proposed method initially classifies local convexities from
      imperfect MC vertices based on sliced volumetric data. Experimental results show
      that continuous surfaces are obtained from imperfect silhouette images of both
      convex and nonconvex objects.

PMID- 18632337
TI  - Structural similarity quality metrics in a coding context: exploring the space of
      realistic distortions.
AB  - Perceptual image quality metrics have explicitly accounted for human visual
      system (HVS) sensitivity to subband noise by estimating just noticeable
      distortion (JND) thresholds. A recently proposed class of quality metrics, known
      as structural similarity metrics (SSIM), models perception implicitly by taking
      into account the fact that the HVS is adapted for extracting structural
      information from images. We evaluate SSIM metrics and compare their performance
      to traditional approaches in the context of realistic distortions that arise from
      compression and error concealment in video compression/transmission applications.
      In order to better explore this space of distortions, we propose models for
      simulating typical distortions encountered in such applications. We compare
      specific SSIM implementations both in the image space and the wavelet domain;
      these include the complex wavelet SSIM (CWSSIM), a translation-insensitive SSIM
      implementation. We also propose a perceptually weighted multiscale variant of
      CWSSIM, which introduces a viewing distance dependence and provides a natural way
      to unify the structural similarity approach with the traditional JND-based
      perceptual approaches.

PMID- 18632338
TI  - Infrared image enhancement using H(infinity) bounds for surveillance
      applications.
AB  - In this paper, two algorithms have been presented to enhance the infrared (IR)
      images. Using the autoregressive moving average model structure and H(infinity)
      optimal bounds, the image pixels are mapped from the IR pixel space into normal
      optical image space, thus enhancing the IR image for improved visual quality.
      Although H(infinity)-based system identification algorithms are very common now,
      they are not quite suitable for real-time applications owing to their complexity.
      However, many variants of such algorithms are possible that can overcome this
      constraint. Two such algorithms have been developed and implemented in this
      paper. Theoretical and algorithmic results show remarkable enhancement in the
      acquired images. This will help in enhancing the visual quality of IR images for
      surveillance applications.

PMID- 18632339
TI  - Nonlinear regularized reaction-diffusion filters for denoising of images with
      textures.
AB  - Denoising is always a challenging problem in natural imaging and geophysical data
      processing. In this paper, we consider the denoising of texture images using a
      nonlinear reaction-diffusion equation and directional wavelet frames. In our
      model, a curvelet shrinkage is used for regularization of the diffusion process
      to preserve important features in the diffusion smoothing and a wave atom
      shrinkage is used as the reaction in order to preserve and enhance interesting
      oriented textures. We derive a digital reaction-diffusion filter that lives on
      graphs and show convergence of the corresponding iteration process. Experimental
      results and comparisons show very good performance of the proposed model for
      texture-preserving denoising.

PMID- 18632340
TI  - A variational method for geometric regularization of vascular segmentation in
      medical images.
AB  - In this paper, a level-set-based geometric regularization method is proposed
      which has the ability to estimate the local orientation of the evolving front and
      utilize it as shape induced information for anisotropic propagation. We show that
      preserving anisotropic fronts can improve elongations of the extracted
      structures, while minimizing the risk of leakage. To that end, for an evolving
      front using its shape-offset level-set representation, a novel energy functional
      is defined. It is shown that constrained optimization of this functional results
      in an anisotropic expansion flow which is usefull for vessel segmentation. We
      have validated our method using synthetic data sets, 2-D retinal angiogram images
      and magnetic resonance angiography volumetric data sets. A comparison has been
      made with two state-of-the-art vessel segmentation methods. Quantitative results,
      as well as qualitative comparisons of segmentations, indicate that our
      regularization method is a promising tool to improve the efficiency of both
      techniques.

PMID- 18632341
TI  - An orientation-selective orthogonal lapped transform.
AB  - A novel critically sampled orientation-selective orthogonal lapped transform
      called the lapped Hartley transform (LHT) is derived. In a first step,
      overlapping basis functions are generated by modulating basis functions of a 2-D
      block Hartley transform by a cosine wave. To achieve invertibility and
      orthogonality, an iterative filter is applied as prefilter in the analysis and as
      postfilter in the synthesis operation, respectively. Alternatively, filtering can
      be restricted to analysis or synthesis, ending up with a biorthogonal transform
      (LHT-PR, LHT-PO). A statistical analysis based on a 4000-image data base shows
      that the LHT and LHT-PO have better redundancy removal properties than other
      block or lapped transforms. Finally, image compression and noise removal examples
      are given, showing the advantages of the LHT especially in images containing
      oriented textures.

PMID- 18632342
TI  - Analysis and compensation of rolling shutter effect.
AB  - Due to the sequential-readout structure of complementary metal-oxide
      semiconductor image sensor array, each scanline of the acquired image is exposed
      at a different time, resulting in the so-called electronic rolling shutter that
      induces geometric image distortion when the object or the video camera moves
      during image capture. In this paper, we propose an image processing technique
      using a planar motion model to address the problem. Unlike previous methods that
      involve complex 3-D feature correspondences, a simple approach to the analysis of
      inter- and intraframe distortions is presented. The high-resolution velocity
      estimates used for restoring the image are obtained by global motion estimation,
      BEzier curve fitting, and local motion estimation without resort to
      correspondence identification. Experimental results demonstrate the effectiveness
      of the algorithm.

PMID- 18632343
TI  - A subspace model-based approach to face relighting under unknown lighting and
      poses.
AB  - We present a new approach to face relighting by jointly estimating the pose,
      reflectance functions, and lighting from as few as one image of a face. Upon such
      estimation, we can synthesize the face image under any prescribed new lighting
      condition. In contrast to commonly used face shape models or shape-dependent
      models, we neither recover nor assume the 3-D face shape during the estimation
      process. Instead, we train a pose- and pixel-dependent subspace model of the
      reflectance function using a face database that contains samples of pose and
      illumination for a large number of individuals (e.g., the CMU PIE database and
      the Yale database). Using this subspace model, we can estimate the pose, the
      reflectance functions, and the lighting condition of any given face image. Our
      approach lends itself to practical applications thanks to many desirable
      properties, including the preservation of the non-Lambertian skin reflectance
      properties and facial hair, as well as reproduction of various shadows on the
      face. Extensive experiments show that, compared to recent representative face
      relighting techniques, our method successfully produces better results, in terms
      of subjective and objective quality, without reconstructing a 3-D shape.

PMID- 18632344
TI  - Optimal denoising in redundant representations.
AB  - Image denoising methods are often designed to minimize mean-squared error (MSE)
      within the subbands of a multiscale decomposition. However, most high-quality
      denoising results have been obtained with overcomplete representations, for which
      minimization of MSE in the subband domain does not guarantee optimal MSE
      performance in the image domain. We prove that, despite this suboptimality, the
      expected image-domain MSE resulting from applying estimators to subbands that are
      made redundant through spatial replication of basis functions (e.g., cycle
      spinning) is always less than or equal to that resulting from applying the same
      estimators to the original nonredundant representation. In addition, we show that
      it is possible to further exploit overcompleteness by jointly optimizing the
      subband estimators for image-domain MSE. We develop an extended version of
      Stein's unbiased risk estimate (SURE) that allows us to perform this optimization
      adaptively, for each observed noisy image. We demonstrate this methodology using
      a new class of estimator formed from linear combinations of localized "bump"
      functions that are applied either pointwise or on local neighborhoods of subband
      coefficients. We show through simulations that the performance of these
      estimators applied to overcomplete subbands and optimized for image-domain MSE is
      substantially better than that obtained when they are optimized within each
      subband. This performance is, in turn, substantially better than that obtained
      when they are optimized for use on a nonredundant representation.

PMID- 18632345
TI  - A multiple description coding and delivery scheme for motion-compensated fine
      granularity scalable video.
AB  - Motion-compensated fine-granularity scalability (MC-FGS) with leaky prediction
      has been shown to provide an efficient tradeoff between compression gain and
      error resilience, facilitating the transmission of video over dynamic channel
      conditions. In this paper, we propose an n-channel symmetric motion-compensated
      multiple description (MD) coding and transmission scheme for the delivery of
      scalable video over orthogonal frequency division multiplexed systems, utilizing
      the concepts of partial and leaky predictions. We investigate the proposed MD
      coding and transmission scheme using a cross-layer design perspective. In
      particular, we construct the symmetric motion-compensated MD codes based on the
      diversity order of the channel, defined as the ratio of the overall bandwidth of
      the system to the coherence bandwidth of the channel. We show that knowing the
      diversity order of a physical channel can assist an MC-FGS video coder in
      selecting the motion-compensation prediction point, as well as on the use of
      leaky prediction. More importantly, we illustrate how the side information can
      reduce the drift management problem associated with the construction of symmetric
      motion-compensated MD codes. We provide results based on both an information
      theoretic approach and simulations.

PMID- 18632346
TI  - Blue-noise multitone dithering.
AB  - The introduction of the blue-noise spectra-high-frequency white noise with
      minimal energy at low frequencies-has had a profound impact on digital halftoning
      for binary display devices, such as inkjet printers, because it represents an
      optimal distribution of black and white pixels producing the illusion of a given
      shade of gray. The blue-noise model, however, does not directly translate to
      printing with multiple ink intensities. New multilevel printing and display
      technologies require the development of corresponding quantization algorithms for
      continuous tone images, namely multitoning. In order to define an optimal
      distribution of multitone pixels, this paper develops the theory and design of
      multitone, blue-noise dithering. Here, arbitrary multitone dot patterns are
      modeled as a layered superposition of stack-constrained binary patterns.
      Multitone blue-noise exhibits minimum energy at low frequencies and a staircase
      like, ascending, spectral pattern at higher frequencies. The optimum spectral
      profile is described by a set of principal frequencies and amplitudes whose
      calculation requires the definition of a spectral coherence structure governing
      the interaction between patterns of dots of different intensities. Efficient
      algorithms for the generation of multitone, blue-noise dither patterns are also
      introduced.

PMID- 18632347
TI  - Noise and signal estimation in magnitude MRI and Rician distributed images: a
      LMMSE approach.
AB  - A new method for noise filtering in images that follow a Rician model-with
      particular attention to magnetic resonance imaging-is proposed. To that end, we
      have derived a (novel) closed-form solution of the linear minimum mean square
      error (LMMSE) estimator for this distribution. Additionally, a set of methods
      that automatically estimate the noise power are developed. These methods use
      information of the sample distribution of local statistics of the image, such as
      the local variance, the local mean, and the local mean square value. Accordingly,
      the dynamic estimation of noise leads to a recursive version of the LMMSE, which
      shows a good performance in both noise cleaning and feature preservation. This
      paper also includes the derivation of the probability density function of several
      local sample statistics for the Rayleigh and Rician model, upon which the
      estimators are built.

PMID- 18632348
TI  - Statistical properties of bit-plane probability model and its application in
      supervised texture classification.
AB  - The modeling of wavelet subband histograms via the product Bernoulli
      distributions (PBD) has received a lot of interest and the PBD model has been
      applied successfully in texture image retrieval. In order to fully understand the
      usefulness and effectiveness of the PBD model and its associated signature,
      namely, the bit-plane probability (BP) signature on image processing
      applications, we discuss and investigate some of their statistical properties.
      These properties would help to clarify the sufficiency of the BP signature to
      characterize wavelet subbands, which, in turn, justifies its use in real time
      applications. We apply the BP signature on supervised texture classification
      problem and experimental results suggest that the weighted L(1)-norm (rather than
      the standard L (1)-norm) should be used for the BP signature. Comparative
      classification experiments show that our method outperforms the current state-of
      the-art Generalized Gaussian Density approaches.

PMID- 18632349
TI  - Automatic active model initialization via Poisson inverse gradient.
AB  - Active models have been widely used in image processing applications. A crucial
      stage that affects the ultimate active model performance is initialization. This
      paper proposes a novel automatic initialization approach for parametric active
      models in both 2-D and 3-D. The PIG initialization method exploits a novel
      technique that essentially estimates the external energy field from the external
      force field and determines the most likely initial segmentation. Examples and
      comparisons with two state-of-the- art automatic initialization methods are
      presented to illustrate the advantages of this innovation, including the ability
      to choose the number of active models deployed, rapid convergence, accommodation
      of broken edges, superior noise robustness, and segmentation accuracy.

PMID- 18632350
TI  - Texture analysis and classification with linear regression model based on wavelet
      transform.
AB  - The wavelet transform as an important multiresolution analysis tool has already
      been commonly applied to texture analysis and classification. Nevertheless, it
      ignores the structural information while capturing the spectral information of
      the texture image at different scales. In this paper, we propose a texture
      analysis and classification approach with the linear regression model based on
      the wavelet transform. This method is motivated by the observation that there
      exists a distinctive correlation between the sample images, belonging to the same
      kind of texture, at different frequency regions obtained by 2-D wavelet packet
      transform. Experimentally, it was observed that this correlation varies from
      texture to texture. The linear regression model is employed to analyze this
      correlation and extract texture features that characterize the samples.
      Therefore, our method considers not only the frequency regions but also the
      correlation between these regions. In contrast, the pyramid-structured wavelet
      transform (PSWT) and the tree-structured wavelet transform (TSWT) do not consider
      the correlation between different frequency regions. Experiments show that our
      method significantly improves the texture classification rate in comparison with
      the multiresolution methods, including PSWT, TSWT, the Gabor transform, and some
      recently proposed methods derived from these.

PMID- 18632351
TI  - Cost aggregation and occlusion handling with WLS in stereo matching.
AB  - This paper presents a novel method for cost aggregation and occlusion handling
      for stereo matching. In order to estimate optimal cost, given a per-pixel
      difference image as observed data, we define an energy function and solve the
      minimization problem by solving the iterative equation with the numerical method.
      We improve performance and increase the convergence rate by using several
      acceleration techniques such as the Gauss-Seidel method, the multiscale approach,
      and adaptive interpolation. The proposed method is computationally efficient
      since it does not use color segmentation or any global optimization techniques.
      For occlusion handling, which has not been performed effectively by any
      conventional cost aggregation approaches, we combine the occlusion problem with
      the proposed minimization scheme. Asymmetric information is used so that few
      additional computational loads are necessary. Experimental results show that
      performance is comparable to that of many state-of-the-art methods. The proposed
      method is in fact the most successful among all cost aggregation methods based on
      standard stereo test beds.

PMID- 18632352
TI  - Occlusion-aware optical flow estimation.
AB  - Optical flow can be reliably estimated between areas visible in two images, but
      not in occlusion areas. If optical flow is needed in the whole image domain, one
      approach is to use additional views of the same scene. If such views are
      unavailable, an often-used alternative is to extrapolate optical flow in
      occlusion areas. Since the location of such areas is usually unknown prior to
      optical flow estimation, this is usually performed in three steps. First,
      occlusion-ignorant optical flow is estimated, then occlusion areas are identified
      using the estimated (unreliable) optical flow, and, finally, the optical flow is
      corrected using the computed occlusion areas. This approach, however, does not
      permit interaction between optical flow and occlusion estimates. In this paper,
      we permit such interaction by proposing a variational formulation that jointly
      computes optical flow, implicitly detects occlusions and extrapolates optical
      flow in occlusion areas. The extrapolation mechanism is based on anisotropic
      diffusion and uses the underlying image gradient to preserve structure, such as
      optical flow discontinuities. Our results show significant improvements in the
      computed optical flow fields over other approaches, both qualitatively and
      quantitatively.

PMID- 18632353
TI  - Fast human detection using a novel boosted cascading structure with meta stages.
AB  - We propose a method that can detect humans in a single image based on a novel
      cascaded structure. In our approach, both intensity-based rectangle features and
      gradient-based 1-D features are employed in the feature pool for weak-learner
      selection. The Real AdaBoost algorithm is used to select critical features from a
      combined feature set and learn the classifiers from the training images for each
      stage of the cascaded structure. Instead of using the standard boosted cascade,
      the proposed method employs a novel cascaded structure that exploits both the
      stage-wise classification information and the interstage cross-reference
      information. We introduce meta-stages to enhance the detection performance of a
      boosted cascade. Experiment results show that the proposed approach achieves high
      detection accuracy and efficiency.

PMID- 18632354
TI  - Indexing of satellite images with different resolutions by wavelet features.
AB  - Space agencies are rapidly building up massive image databases. A particularity
      of these databases is that they are made of images with different, but known,
      resolutions. In this paper, we introduce a new scheme allowing us to compare and
      index images with different resolutions. This scheme relies on a simplified
      acquisition model of satellite images and uses continuous wavelet decompositions.
      We establish a correspondence between scales which permits us to compare wavelet
      decompositions of images having different resolutions. We validate the approach
      through several matching and classification experiments, and we show that taking
      the acquisition process into account yields better results than just using
      scaling properties of wavelet features.

PMID- 18632355
TI  - Multichannel electrocardiogram decomposition using periodic component analysis.
AB  - In this letter, we propose the application of the generalized eigenvalue
      decomposition for the decomposition of multichannel electrocardiogram (ECG)
      recordings. The proposed method uses a modified version of a previously presented
      measure of periodicity and a phase-wrapping of the RR-interval, for extracting
      the "most periodic" linear mixtures of a recorded dataset. It is shown that the
      method is an improved extension of conventional source separation techniques,
      specifically customized for ECG signals. The method is therefore of special
      interest for the decomposition and compression of multichannel ECG, and for the
      removal of maternal ECG artifacts from fetal ECG recordings.

PMID- 18632356
TI  - Two-dimensional time-domain inverse scattering for quantitative analysis of
      breast composition.
AB  - Forward-backward time-stepping is a unique approach for solving electromagnetic
      inverse scattering problems in the time domain. In this paper, the technique is
      applied to a realistic, heterogeneous breast model. The ability to detect a 5-mm
      diameter malignancy and provide substantial quantitative information about the
      breast's composition is demonstrated.

PMID- 18632357
TI  - Modeling the nonlinear context dependency of the neural integrator in the
      vestibuloocular reflex.
AB  - A neural integrator (NI) is presumed to exist in the oculomotor system to assist
      in numerous tasks such as maintaining gaze on imaginary targets in the dark. It
      is shared by all ocular reflexes including the vestibuloocular reflex (VOR). It
      has been widely accepted that the NI acts as a "perfect" integrator even in the
      dark with time constants as large as 1950s. However, the NI time constant is
      often less than ideal and its value can also be dependent on context [W. W. P.
      Chan and H. L. Galiana, "Integrator function in the oculomotor system is
      dependent on sensory context," J. Neurophysiol., vol. 93, pp. 3709--3717, Feb.
      2005.]. In this paper, a nonlinear feedback model is postulated to model the
      context-dependent properties of the NI. Algorithms are first developed and
      validated to fit both linear and nonlinear NI models to experimental data in the
      presence of ocular nystagmus. Preliminary results indicate that even normal
      subjects can have a nonlinear VOR and NI.

PMID- 18632358
TI  - Support vector machine-based classification scheme for myoelectric control
      applied to upper limb.
AB  - This paper proposes and evaluates the application of support vector machine (SVM)
      to classify upper limb motions using myoelectric signals. It explores the optimum
      configuration of SVM-based myoelectric control, by suggesting an advantageous
      data segmentation technique, feature set, model selection approach for SVM, and
      postprocessing methods. This work presents a method to adjust SVM parameters
      before classification, and examines overlapped segmentation and majority voting
      as two techniques to improve controller performance. A SVM, as the core of
      classification in myoelectric control, is compared with two commonly used
      classifiers: linear discriminant analysis (LDA) and multilayer perceptron (MLP)
      neural networks. It demonstrates exceptional accuracy, robust performance, and
      low computational load. The entropy of the output of the classifier is also
      examined as an online index to evaluate the correctness of classification; this
      can be used by online training for long-term myoelectric control operations.

PMID- 18632359
TI  - Automatic selection of the threshold value R for approximate entropy.
AB  - Calculation of approximate entropy (ApEn) requires a priori determination of two
      unknown parameters, m and r. While the recommended values of r, in the range of
      0.1-0.2 times the standard deviation of the signal, have been shown to be
      applicable for a wide variety of signals, in certain cases, r values within this
      prescribed range can lead to an incorrect assessment of the complexity of a given
      signal. To circumvent this limitation, we recently advocated finding the maximum
      ApEn value by assessing all values of r from 0 to 1, and found that maximum ApEn
      does not always occur within the prescribed range of r values. Our results
      indicate that finding the maximum ApEn leads to the correct interpretation of a
      signal's complexity. One major limitation, however, is that the calculation of
      all choices of r values is often impractical due to the computational burden. Our
      new method, based on a heuristic stochastic model, overcomes this computational
      burden, and leads to the automatic selection of the maximum ApEn value for any
      given signal. Based on Monte Carlo simulations, we derive general equations that
      can be used to estimate the maximum ApEn with high accuracy for a given value of
      m. Application to both synthetic and experimental data confirmed the advantages
      claimed with the proposed approach.

PMID- 18632360
TI  - Accelerometers and force sensing resistors for optimal control of walking of a
      hemiplegic.
AB  - We developed a method for use of accelerometers and force sensing resistors
      (FSRs) within an optimal controller of walking for hemiplegic individuals. The
      data from four dual-axis accelerometers and four FSRs were inputs, while six
      muscle activation profiles were outputs. The controller includes two stages: 1)
      estimating the target gait pattern using artificial neural networks; and 2)
      optimal control minimizing tracking errors (from the estimated gait pattern) and
      muscle efforts. The controller was tested using data collected from six healthy
      subjects walking at five speeds (0.6-1.4 m/s). The average root mean square
      errors (RMSEs) normalized by the peak-to-peak value of the target signals
      [normalized RMSE (NRMSE)] were below 6%, 7%, 8%, and 3% for estimation of joint
      angles, hip acceleration, ground reaction force, and movement of the center of
      pressure, respectively. Using the estimated data as inputs, the simulation
      generated the target healthy-like gait patterns and reproducible muscle
      activation profiles in 90% of 300 tested gait trials. Overall tracking NRMSE was
      between 2% and 9%. The optimal controller was developed for testing the
      feasibility of healthy-like gait patterns in hemiplegic individuals, and
      generating a knowledge base that is required for the synthesis of a sensory
      driven control of walking assisted by functional electrical stimulation.

PMID- 18632362
TI  - Multiclass common spatial patterns and information theoretic feature extraction.
AB  - We address two shortcomings of the common spatial patterns (CSP) algorithm for
      spatial filtering in the context of brain--computer interfaces (BCIs) based on
      electroencephalography/magnetoencephalography (EEG/MEG): First, the question of
      optimality of CSP in terms of the minimal achievable classification error remains
      unsolved. Second, CSP has been initially proposed for two-class paradigms.
      Extensions to multiclass paradigms have been suggested, but are based on
      heuristics. We address these shortcomings in the framework of information
      theoretic feature extraction (ITFE). We show that for two-class paradigms, CSP
      maximizes an approximation of mutual information of extracted EEG/MEG components
      and class labels. This establishes a link between CSP and the minimal
      classification error. For multiclass paradigms, we point out that CSP by joint
      approximate diagonalization (JAD) is equivalent to independent component analysis
      (ICA), and provide a method to choose those independent components (ICs) that
      approximately maximize mutual information of ICs and class labels. This
      eliminates the need for heuristics in multiclass CSP, and allows incorporating
      prior class probabilities. The proposed method is applied to the dataset IIIa of
      the third BCI competition, and is shown to increase the mean classification
      accuracy by 23.4% in comparison to multiclass CSP.

PMID- 18632361
TI  - A subband-based information measure of EEG during brain injury and recovery after
      cardiac arrest.
AB  - We propose an improved quantitative measure of EEG during brain injury and
      recovery after cardiac arrest. In our previous studies, we proposed a measure,
      information quantity (IQ), to detect the early effects of temperature
      manipulation on the EEG signals recorded from the scalp. IQ incorporates the
      wavelet transform and the Shannon entropy in full bands from delta to gamma.
      Unlike IQ, here we separately calculate IQ in each subband, i.e., the new measure
      is IQ in each subband. We will call it subband IQ (SIQ). We demonstrate the
      performance of the proposed method by comparing SIQ with IQ in terms of how well
      the meausres predict actual neurological outcomes. Thirteen rats, based on 7-min
      cardiac arrest were used. The experimental results show that the proposed measure
      was more highly correlated to neurological outcome than IQ.

PMID- 18632363
TI  - SNR-adaptive stream weighting for audio-MES ASR.
AB  - Myoelectric signals (MESs) from the speaker's mouth region have been successfully
      shown to improve the noise robustness of automatic speech recognizers (ASRs),
      thus promising to extend their usability in implementing noise-robust ASR. In the
      recognition system presented herein, extracted audio and facial MES features were
      integrated by a decision fusion method, where the likelihood score of the audio
      MES observation vector was given by a linear combination of class-conditional
      observation log-likelihoods of two classifiers, using appropriate weights. We
      developed a weighting process adaptive to SNRs. The main objective of the paper
      involves determining the optimal SNR classification boundaries and constructing a
      set of optimum stream weights for each SNR class. These two parameters were
      determined by a method based on a maximum mutual information criterion. Acoustic
      and facial MES data were collected from five subjects, using a 60-word
      vocabulary. Four types of acoustic noise including babble, car, aircraft, and
      white noise were acoustically added to clean speech signals with SNR ranging from
      -14 to 31 dB. The classification accuracy of the audio ASR was as low as 25.5%.
      Whereas, the classification accuracy of the MES ASR was 85.2%. The classification
      accuracy could be further improved by employing the proposed audio-MES weighting
      method, which was as high as 89.4% in the case of babble noise. A similar result
      was also found for the other types of noise.

PMID- 18632364
TI  - Effect of lesion morphology on microwave signature in 2-D ultra-wideband breast
      imaging.
AB  - This paper studies the possibility of distinguishing between benign and malignant
      masses by exploiting the morphology-dependent temporal and spectral
      characteristics of their microwave backscatter response in ultra-wideband breast
      cancer detection. The spiculated border profiles of 2-D breast masses are
      generated by modifying the baseline elliptical rings based upon the irregularity
      of their peripheries. Furthermore, the single- and multilayer lesion models are
      used to characterize a distinct mass region followed by a sharp transition to
      background, and a blurred mass border exhibiting a gradual transition to
      background, respectively. Subsequently, the complex natural resonances (CNRs) of
      the backscatter microwave signature can be derived from the late-time target
      response and reveal diagnostically useful information. The fractional sequence
      CLEAN algorithm is proposed to estimate the lesions' delay intervals and identify
      the late-time responses. Finally, it is shown through numerical examples that the
      locations of dominant CNRs are dependent on the lesion morphologies, where 2-D
      computational breast phantoms with single and multiple lesions are investigated.
      The analysis is of potential use for discrimination between benign and malignant
      lesions, where the former usually possesses a better-defined, more compact shape
      as opposed to the latter.

PMID- 18632365
TI  - A morphology-based approach for interslice interpolation of anatomical slices
      from volumetric images.
AB  - This paper proposes a new morphology-based approach for the interslice
      interpolation of current transformer (CT) and MRI datasets composed of parallel
      slices. Our approach is object based and accepts as input data binary slices
      belonging to the same anatomical structure. Such slices may contain one or more
      regions, since topological changes between two adjacent slices may occur. Our
      approach handles explicitly interslice topology changes by decomposing a many-to
      many correspondence into three fundamental cases: one-to-one, one-to-many, and
      zero-to-one correspondences. The proposed interpolation process is iterative. One
      iteration of this process computes a transition sequence between a pair of
      corresponding input slices, and selects the element located at equal distance
      from the input slices. This algorithmic design yields a gradual, smooth change of
      shape between the input slices. Therefore, the main contribution of our approach
      is its ability to interpolate between two anatomic shapes by creating a smooth,
      gradual change of shape, and without generating over-smoothed interpolated
      shapes.

PMID- 18632366
TI  - A high-frame rate duplex ultrasound biomicroscopy for small animal imaging in
      vivo.
AB  - Much of the current knowledge of human cardiovascular pathologies and treatment
      strategies has been gained from understanding the cardiac physiologies and
      functions in small animal models, such as mice, rats, and zebrafish. In this
      paper, we present the development of a high-frame-rate duplex ultrasound
      biomicroscopy (UBM) capable of B-mode imaging and pulsed-wave (PW) Doppler
      measurement for in vivo cardiovascular investigation in small animals. A frame
      rate of 200 frames per second (fps) was accomplished at a view of 5 mm x 8 mm,
      using a novel high-speed sector probe and specially designed lightweight
      transducers. In a reduced lateral view of 1.2 mm, a frame rate of 400 fps was
      achieved to examine more detailed cardiac motion. The UBM utilized transducers
      with different center frequencies (40-75 MHz) and geometries, which made it
      useful for various applications in small animal cardiac imaging. The highest
      spatial resolution the UBM achieved was 25 microm x 56 microm. In addition, the
      image-guided PW Doppler implemented in the UBM demonstrated the detection of the
      velocity of a moving wire as low as 0.1 mm/s, and flow in a polyimide tube as
      small as 200 microm in diameter. Furthermore, the UBM achieved a 15- microV
      minimal detectable signal and a 60-dB dynamic range using a low-cost PCB-based
      design. Finally, sample in vivo cardiac images of mouse and zebrafish hearts were
      given. These results showed that the UBM integrated with B-mode and PW Doppler is
      useful to investigate the pathophysiological mechanism in the cardiovascular
      studies.

PMID- 18632367
TI  - Tooth-click control of a hands-free computer interface.
AB  - People with severe upper limb paralysis use devices that monitor head movements
      to control computer cursors. The three most common methods for producing mouse
      button clicks are dwell-time, sip-and-puff control, and voice-recognition. Here,
      we tested a new method in which small tooth-clicks were detected by an
      accelerometer contacting the side of the head. The resulting signals were paired
      with head tracking technology to provide combined cursor and button control. This
      system was compared with sip-and-puff control and dwell-time selection. A group
      of 17 people with disabilities and ten people without disabilities tested each
      system by producing mouse clicks as inputs to two software programs. Tooth
      click/head-mouse control was much faster than dwell-time control and not quite as
      fast as sip-and-puff control, but it was more reliable and less cumbersome than
      the latter.

PMID- 18632368
TI  - The hyperbolic strength-duration relationship of defibrillation threshold.
AB  - Defibrillation with square-wave pulses has proved to possess hyperbolic strength
      duration relationship. Does such a hyperbolic relation also exist for
      exponentially decaying pulses as they are commonly used today? This paper
      hypothesizes that exponentially decaying pulses obey hyperbolic strength-duration
      relationship, calculates the consequences, and advises of how such thresholds
      should be investigated. If the strength-duration relationship exists for current,
      the corresponding charge threshold must be a Weiss' straight threshold line. In
      analogy, for exponentially decaying pulses, the integral of the amplitude over
      pulse duration (PD) must be calculated as a function of PD. If this function is
      linearly correlated, the mean voltage possesses a hyperbolic strength-duration
      relationship, whereas the peak voltage does not. Peak amplitude curves possess
      minima shifting to the right with increasing time constant RC limiting the
      allowed range of useful PDs. To prove that exponentially decaying pulses have a
      hyperbolic relationship, testing must be done in six steps that are demonstrated
      with results published in literature. Mean voltages have, indeed, hyperbolic
      strength-duration relationship. Chronaxie is not calculated correctly as long as
      peak voltage thresholds are correlated and PDs are greater than allowed.

PMID- 18632369
TI  - Large-scale, high-resolution data acquisition system for extracellular recording
      of electrophysiological activity.
AB  - A platform for high spatial and temporal resolution electrophysiological
      recordings of in vitro electrogenic cell cultures handling 4096 electrodes at a
      full frame rate of 8 kHz is presented and validated by means of cardiomyocyte
      cultures. Based on an active pixel sensor device implementing an array of
      metallic electrodes, the system provides acquisitions at spatial resolutions of
      42 microm on an active area of 2.67 mm x 2.67 mm, and in the zooming mode,
      temporal resolutions down to 8 micros on 64 randomly selected electrodes. The low
      noise performances of the integrated amplifier (11 microV (rms)) combined with a
      hardware implementation inspired by image/video processing concepts enable high
      resolution acquisitions with real-time preprocessing capabilities adapted to the
      handling of the large amount of acquired data.

PMID- 18632370
TI  - Multivariate reconstruction of functional networks from cortical sources dynamics
      in MEG/EEG.
AB  - In this paper, we present a simple method to find networks of time-correlated
      brain sources, using a singular value decomposition (SVD) analysis of the source
      matrix estimated after any linear distributed inverse problem in
      magnetoencephalography (MEG) and electroencephalography (EEG). Despite the high
      dimension of the source space, our method allows for the rapid computation of the
      source matrix. In order to do this, we use the linear relationship between
      sensors and sources, and show that the SVD can be calculated through a simple and
      fast computation. We show that this method allows the estimation of one or
      several global networks of correlated sources without calculating a coupling
      coefficient between all pairs of sources. A series of simulations studies were
      performed to estimate the efficiency of the method. In order to illustrate the
      validity of this approach in experimental conditions, we used real MEG data from
      a visual stimulation task on one test subject and estimated, in different time
      windows of interest, functional networks of correlated sources.

PMID- 18632371
TI  - Finite-element analysis of hepatic cryoablation around a large blood vessel.
AB  - Cryoablation is a minimally invasive ablation technique for primary and
      metastatic hepatic tumors. Inadequate freezing around large blood vessels due to
      the warm blood flow can lead to local recurrence, and thus, necessitates close
      application of a cryoprobe to the large blood vessels. In this study, we
      constructed a perfusion model with an ex vivo bovine liver and ablated the tissue
      around a large blood vessel with one or two cryoprobes applied to the side of the
      vessel. The finite-element computer model developed in our previous study was
      modified to include a blood vessel and its convective heat transfer to the
      vicinity of the blood vessel. We compared the predicted simulation results to
      those acquired from this ex vivo perfusion model. The results indicate that blood
      vessels act as a heat source and generate steep temperature profiles in the area
      next to the large blood vessel. After validation, the maximum allowable distance
      between the cryoprobe and the large blood vessel for successful cryoablation was
      presented. The results of this study should be considered when placing cryoprobes
      in the vicinity of large blood vessels.

PMID- 18632372
TI  - Noninvasive average flow and differential pressure estimation for an implantable
      rotary blood pump using dimensional analysis.
AB  - Accurate noninvasive average flow and differential pressure estimation of
      implantable rotary blood pumps (IRBPs) is an important practical element for
      their physiological control. While most attempts at developing flow and
      differential pressure estimate models have involved purely empirical techniques,
      dimensional analysis utilizes theoretical principles of fluid mechanics that
      provides valuable insights into parameter relationships. Based on data obtained
      from a steady flow mock loop under a wide range of pump operating points and
      fluid viscosities, flow and differential pressure estimate models were thus
      obtained using dimensional analysis. The algorithm was then validated using data
      from two other VentrAssist IRBPs. Linear correlations between estimated and
      measured pump flow over a flow range of 0.5 to 8.0 L/min resulted in a slope of
      0.98 ( R(2) = 0.9848). The average flow error was 0.20 +/- 0.14 L/min (mean +/-
      standard deviation) and the average percentage error was 5.79%. Similarly, linear
      correlations between estimated and measured pump differential pressure resulted
      in a slope of 1.027 ( R(2) = 0.997) over a pressure range of 60 to 180 mmHg. The
      average differential pressure error was 1.84 +/- 1.54 mmHg and the average
      percentage error was 1.51%.

PMID- 18632373
TI  - Photon density measured over a cut surface: implications for optical mapping of
      the heart.
AB  - During optical mapping of the heart, the signal represents a weighted average of
      the transmembrane potential. Researchers sometimes illuminate the epicardium and
      record over a cut surface. My goal is to compare their signal to the photon
      density within an intact tissue. Does cutting the tissue affect the signal?

PMID- 18632374
TI  - Computational assessment of combinations of gait modifications for knee
      osteoarthritis rehabilitation.
AB  - Gait modification is a noninvasive strategy for reducing the external knee
      adduction torque in patients with medial compartment knee osteoarthritis.
      Recently, a novel "medial thrust" gait pattern characterized by knee
      medialization during stance phase has been shown to reduce both adduction torque
      peaks significantly. While changes in footpath (i.e., toe out angle and stance
      width) also affect the adduction torque peaks, the extent to which footpath
      changes may alter the effectiveness of medial thrust gait is unknown. This study
      used a validated patient-specific computational model to investigate this issue.
      A dynamic optimization framework that accurately predicted adduction torque
      changes caused by knee medialization or footpath alteration for a specific
      patient was modified to predict the simultaneous effect of both factors. Medial
      thrust gait optimizations were then performed for the same patient using imposed
      footpath alterations consisting of all possible combinations of three toe out
      angles (nominal +/- 15 degrees) and three stance widths (nominal +/- 50 mm).
      Overall, predicted adduction torque reductions produced by medial thrust gait
      were relatively insensitive to footpath alterations. The 32%-34% reduction in
      both peaks achieved with the nominal footpath was augmented by at most 9% and
      reduced by at most 3% for the altered footpaths. When combined with knee
      medialization, footpath alterations would likely have only a secondary effect on
      knee adduction torque reductions for this particular patient.

PMID- 18632375
TI  - Assessing aortic stenosis using sample entropy of the phonocardiographic signal
      in dogs.
AB  - In aortic valve stenosis (AS), heart murmurs arise as an effect of turbulent
      blood flow distal to the obstructed valves. With increasing AS severity, the flow
      becomes more unstable, and the ensuing murmur becomes more complex. We
      hypothesize that these hemodynamic flow changes can be quantified based on the
      complexity of the phonocardiographic (PCG) signal. In this study, sample entropy
      (SampEn) was investigated as a measure of complexity using a dog model. Twenty
      seven boxer dogs with various degrees of AS were examined with Doppler
      echocardiography, and the peak aortic flow velocity ( V(max)) was used as a
      reference of AS severity. SampEn correlated to V(max) with R = 0.70 using
      logarithmic regression. In a separate analysis, significant differences were
      found between physiologic murmurs and murmurs caused by AS ( p << 0.05), and the
      area under a receiver operating characteristic curve was calculated to 0.96.
      Comparison with previously presented PCG measures for AS assessment showed
      improved performance when using SampEn, especially for differentiation between
      physiological murmurs and murmurs caused by mild AS. Studies in patients will be
      needed to properly assess the technique in humans.

PMID- 18632376
TI  - Higher level application of ADP: a next phase for the control field?
AB  - Two distinguishing features of humanlike control vis-a-vis current technological
      control are the ability to make use of experience while selecting a control
      policy for distinct situations and the ability to do so faster and faster as more
      experience is gained (in contrast to current technological implementations that
      slow down as more knowledge is stored). The notions of context and context
      discernment are important to understanding this human ability. Whereas methods
      known as adaptive control and learning control focus on modifying the design of a
      controller as changes in context occur, experience-based (EB) control entails
      selecting a previously designed controller that is appropriate to the current
      situation. Developing the EB approach entails a shift of the technologist's focus
      "up a level" away from designing individual (optimal) controllers to that of
      developing online algorithms that efficiently and effectively select designs from
      a repository of existing controller solutions. A key component of the notions
      presented here is that of higher level learning algorithm. This is a new
      application of reinforcement learning and, in particular, approximate dynamic
      programming, with its focus shifted to the posited higher level, and is employed,
      with very promising results. The author's hope for this paper is to inspire and
      guide future work in this promising area.

PMID- 18632377
TI  - Issues on stability of ADP feedback controllers for dynamical systems.
AB  - This paper traces the development of neural-network (NN)-based feedback
      controllers that are derived from the principle of adaptive/approximate dynamic
      programming (ADP) and discusses their closed-loop stability. Different versions
      of NN structures in the literature, which embed mathematical mappings related to
      solutions of the ADP-formulated problems called "adaptive critics" or "action
      critic" networks, are discussed. Distinction between the two classes of ADP
      applications is pointed out. Furthermore, papers in "model-free" development and
      model-based neurocontrollers are reviewed in terms of their contributions to
      stability issues. Recent literature suggests that work in ADP-based feedback
      controllers with assured stability is growing in diverse forms.

PMID- 18632378
TI  - Hamilton-Jacobi-Bellman equations and approximate dynamic programming on time
      scales.
AB  - The time scales calculus is a key emerging area of mathematics due to its
      potential use in a wide variety of multidisciplinary applications. We extend this
      calculus to approximate dynamic programming (ADP). The core backward induction
      algorithm of dynamic programming is extended from its traditional discrete case
      to all isolated time scales. Hamilton-Jacobi-Bellman equations, the solution of
      which is the fundamental problem in the field of dynamic programming, are
      motivated and proven on time scales. By drawing together the calculus of time
      scales and the applied area of stochastic control via ADP, we have connected two
      major fields of research.

PMID- 18632379
TI  - Random sampling of states in dynamic programming.
AB  - We combine three threads of research on approximate dynamic programming: sparse
      random sampling of states, value function and policy approximation using local
      models, and using local trajectory optimizers to globally optimize a policy and
      associated value function. Our focus is on finding steady-state policies for
      deterministic time-invariant discrete time control problems with continuous
      states and actions often found in robotics. In this paper, we describe our
      approach and provide initial results on several simulated robotics problems.

PMID- 18632380
TI  - Ensemble algorithms in reinforcement learning.
AB  - This paper describes several ensemble methods that combine multiple different
      reinforcement learning (RL) algorithms in a single agent. The aim is to enhance
      learning speed and final performance by combining the chosen actions or action
      probabilities of different RL algorithms. We designed and implemented four
      different ensemble methods combining the following five different RL algorithms:
      Q-learning, Sarsa, actor-critic (AC), QV-learning, and AC learning automaton. The
      intuitively designed ensemble methods, namely, majority voting (MV), rank voting,
      Boltzmann multiplication (BM), and Boltzmann addition, combine the policies
      derived from the value functions of the different RL algorithms, in contrast to
      previous work where ensemble methods have been used in RL for representing and
      learning a single value function. We show experiments on five maze problems of
      varying complexity; the first problem is simple, but the other four maze tasks
      are of a dynamic or partially observable nature. The results indicate that the BM
      and MV ensembles significantly outperform the single RL algorithms.

PMID- 18632381
TI  - A novel infinite-time optimal tracking control scheme for a class of discrete
      time nonlinear systems via the greedy HDP iteration algorithm.
AB  - In this paper, we aim to solve the infinite-time optimal tracking control problem
      for a class of discrete-time nonlinear systems using the greedy heuristic dynamic
      programming (HDP) iteration algorithm. A new type of performance index is defined
      because the existing performance indexes are very difficult in solving this kind
      of tracking problem, if not impossible. Via system transformation, the optimal
      tracking problem is transformed into an optimal regulation problem, and then, the
      greedy HDP iteration algorithm is introduced to deal with the regulation problem
      with rigorous convergence analysis. Three neural networks are used to approximate
      the performance index, compute the optimal control policy, and model the
      nonlinear system for facilitating the implementation of the greedy HDP iteration
      algorithm. An example is given to demonstrate the validity of the proposed
      optimal tracking control scheme.

PMID- 18632382
TI  - Discrete-time nonlinear HJB solution using approximate dynamic programming:
      convergence proof.
AB  - Convergence of the value-iteration-based heuristic dynamic programming (HDP)
      algorithm is proven in the case of general nonlinear systems. That is, it is
      shown that HDP converges to the optimal control and the optimal value function
      that solves the Hamilton-Jacobi-Bellman equation appearing in infinite-horizon
      discrete-time (DT) nonlinear optimal control. It is assumed that, at each
      iteration, the value and action update equations can be exactly solved. The
      following two standard neural networks (NN) are used: a critic NN is used to
      approximate the value function, whereas an action network is used to approximate
      the optimal control policy. It is stressed that this approach allows the
      implementation of HDP without knowing the internal dynamics of the system. The
      exact solution assumption holds for some classes of nonlinear systems and,
      specifically, in the specific case of the DT linear quadratic regulator (LQR),
      where the action is linear and the value quadratic in the states and NNs have
      zero approximation error. It is stressed that, for the LQR, HDP may be
      implemented without knowing the system A matrix by using two NNs. This fact is
      not generally appreciated in the folklore of HDP for the DT LQR, where only one
      critic NN is generally used.

PMID- 18632383
TI  - Reinforcement learning in continuous time and space: interference and not ill
      conditioning is the main problem when using distributed function approximators.
AB  - Many interesting problems in reinforcement learning (RL) are continuous and/or
      high dimensional, and in this instance, RL techniques require the use of function
      approximators for learning value functions and policies. Often, local linear
      models have been preferred over distributed nonlinear models for function
      approximation in RL. We suggest that one reason for the difficulties encountered
      when using distributed architectures in RL is the problem of negative
      interference, whereby learning of new data disrupts previously learned mappings.
      The continuous temporal difference (TD) learning algorithm TD(lambda) was used to
      learn a value function in a limited-torque pendulum swing-up task using a
      multilayer perceptron (MLP) network. Three different approaches were examined for
      learning in the MLP networks; 1) simple gradient descent; 2) vario-eta; and 3) a
      pseudopattern rehearsal strategy that attempts to reduce the effects of
      interference. Our results show that MLP networks can be used for value function
      approximation in this task but require long training times. We also found that
      vario-eta destabilized learning and resulted in a failure of the learning process
      to converge. Finally, we showed that the pseudopattern rehearsal strategy
      drastically improved the speed of learning. The results indicate that
      interference is a greater problem than ill conditioning for this task.

PMID- 18632384
TI  - Incoherent control of quantum systems with wavefunction-controllable subspaces
      via quantum reinforcement learning.
AB  - In this paper, an incoherent control scheme for accomplishing the state control
      of a class of quantum systems which have wavefunction-controllable subspaces is
      proposed. This scheme includes the following two steps: projective measurement on
      the initial state and learning control in the wavefunction-controllable subspace.
      The first step probabilistically projects the initial state into the wavefunction
      controllable subspace. The probability of success is sensitive to the initial
      state; however, it can be greatly improved through multiple experiments on
      several identical initial states even in the case with a small probability of
      success for an individual measurement. The second step finds a local optimal
      control sequence via quantum reinforcement learning and drives the controlled
      system to the objective state through a set of suitable controls. In this
      strategy, the initial states can be unknown identical states, the quantum
      measurement is used as an effective control, and the controlled system is not
      necessarily unitarily controllable. This incoherent control scheme provides an
      alternative quantum engineering strategy for locally controllable quantum
      systems.

PMID- 18632385
TI  - An evolutionary approach toward dynamic self-generated fuzzy inference systems.
AB  - An evolutionary approach toward automatic generation of fuzzy inference systems
      (FISs), termed evolutionary dynamic self-generated fuzzy inference systems
      (EDSGFISs), is proposed in this paper. The structure and parameters of an FIS are
      generated through reinforcement learning, whereas an action set for training the
      consequents of the FIS is evolved via genetic algorithms (GAs). The proposed
      EDSGFIS algorithm can automatically create, delete, and adjust fuzzy rules
      according to the performance of the entire system, as well as evaluation of
      individual fuzzy rules. Simulation studies on a wall-following task by a mobile
      robot show that the proposed EDSGFIS approach is superior to other related
      methods.

PMID- 18632386
TI  - Decentralized Bayesian search using approximate dynamic programming methods.
AB  - We consider decentralized Bayesian search problems that involve a team of
      multiple autonomous agents searching for targets on a network of search points
      operating under the following constraints: 1) interagent communication is
      limited; 2) the agents do not have the opportunity to agree in advance on how to
      resolve equivalent but incompatible strategies; and 3) each agent lacks the
      ability to control or predict with certainty the actions of the other agents. We
      formulate the multiagent search-path-planning problem as a decentralized optimal
      control problem and introduce approximate dynamic heuristics that can be
      implemented in a decentralized fashion. After establishing some analytical
      properties of the heuristics, we present computational results for a search
      problem involving two agents on a 5 x 5 grid.

PMID- 18632387
TI  - Decentralized learning in Markov games.
AB  - Learning automata (LA) were recently shown to be valuable tools for designing
      multiagent reinforcement learning algorithms. One of the principal contributions
      of the LA theory is that a set of decentralized independent LA is able to control
      a finite Markov chain with unknown transition probabilities and rewards. In this
      paper, we propose to extend this algorithm to Markov games--a straightforward
      extension of single-agent Markov decision problems to distributed multiagent
      decision problems. We show that under the same ergodic assumptions of the
      original theorem, the extended algorithm will converge to a pure equilibrium
      point between agent policies.

PMID- 18632388
TI  - Adaptive feedback control by constrained approximate dynamic programming.
AB  - A constrained approximate dynamic programming (ADP) approach is presented for
      designing adaptive neural network (NN) controllers with closed-loop stability and
      performance guarantees. Prior knowledge of the linearized equations of motion is
      used to guarantee that the closed-loop system meets performance and stability
      objectives when the plant operates in a linear parameter-varying (LPV) regime. In
      the presence of unmodeled dynamics or failures, the NN controller adapts to
      optimize its performance online, whereas constrained ADP guarantees that the LPV
      baseline performance is preserved at all times. The effectiveness of an adaptive
      NN flight controller is demonstrated for simulated control failures, parameter
      variations, and near-stall dynamics.

PMID- 18632389
TI  - Adaptive critic learning techniques for engine torque and air-fuel ratio control.
AB  - A new approach for engine calibration and control is proposed. In this paper, we
      present our research results on the implementation of adaptive critic designs for
      self-learning control of automotive engines. A class of adaptive critic designs
      that can be classified as (model-free) action-dependent heuristic dynamic
      programming is used in this research project. The goals of the present learning
      control design for automotive engines include improved performance, reduced
      emissions, and maintained optimum performance under various operating conditions.
      Using the data from a test vehicle with a V8 engine, we developed a neural
      network model of the engine and neural network controllers based on the idea of
      approximate dynamic programming to achieve optimal control. We have developed and
      simulated self-learning neural network controllers for both engine torque (TRQ)
      and exhaust air-fuel ratio (AFR) control. The goal of TRQ control and AFR control
      is to track the commanded values. For both control problems, excellent neural
      network controller transient performance has been achieved.

PMID- 18632390
TI  - Control of nonaffine nonlinear discrete-time systems using reinforcement-learning
      based linearly parameterized neural networks.
AB  - A nonaffine discrete-time system represented by the nonlinear autoregressive
      moving average with eXogenous input (NARMAX) representation with unknown
      nonlinear system dynamics is considered. An equivalent affinelike representation
      in terms of the tracking error dynamics is first obtained from the original
      nonaffine nonlinear discrete-time system so that reinforcement-learning-based
      near-optimal neural network (NN) controller can be developed. The control scheme
      consists of two linearly parameterized NNs. One NN is designated as the critic
      NN, which approximates a predefined long-term cost function, and an action NN is
      employed to derive a near-optimal control signal for the system to track a
      desired trajectory while minimizing the cost function simultaneously. The NN
      weights are tuned online. By using the standard Lyapunov approach, the stability
      of the closed-loop system is shown. The net result is a supervised actor-critic
      NN controller scheme which can be applied to a general nonaffine nonlinear
      discrete-time system without needing the affinelike representation. Simulation
      results demonstrate satisfactory performance of the controller.

PMID- 18632391
TI  - Comparison of adaptive critic-based and classical wide-area controllers for power
      systems.
AB  - An adaptive critic design (ACD)-based damping controller is developed for a
      thyristor-controlled series capacitor (TCSC) installed in a power system with
      multiple poorly damped interarea modes. The performance of this ACD computational
      intelligence-based method is compared with two classical techniques, which are
      observer-based state-feedback (SF) control and linear matrix inequality LMI
      H(infinity) robust control. Remote measurements are used as feedback signals to
      the wide-area damping controller for modulating the compensation of the TCSC. The
      classical methods use a linearized model of the system whereas the ACD method is
      purely measurement-based, leading to a nonlinear controller with fixed
      parameters. A comparative analysis of the controllers' performances is carried
      out under different disturbance scenarios. The ACD-based design has shown
      promising performance with very little knowledge of the system compared to
      classical model-based controllers. This paper also discusses the advantages and
      disadvantages of ACDs, SF, and LMI-H(infinity).

PMID- 18632392
TI  - Direct heuristic dynamic programming for damping oscillations in a large power
      system.
AB  - This paper applies a neural-network-based approximate dynamic programming method,
      namely, the direct heuristic dynamic programming (direct HDP), to a large power
      system stability control problem. The direct HDP is a learning- and approximation
      based approach to addressing nonlinear coordinated control under uncertainty. One
      of the major design parameters, the controller learning objective function, is
      formulated to directly account for network-wide low-frequency oscillation with
      the presence of nonlinearity, uncertainty, and coupling effect among system
      components. Results include a novel learning control structure based on the
      direct HDP with applications to two power system problems. The first case
      involves static var compensator supplementary damping control, which is used to
      provide a comprehensive evaluation of the learning control performance. The
      second case aims at addressing a difficult complex system challenge by providing
      a new solution to a large interconnected power network oscillation damping
      control problem that frequently occurs in the China Southern Power Grid.

PMID- 18632393
TI  - Improved Adaptive-Reinforcement Learning Control for morphing unmanned air
      vehicles.
AB  - This paper presents an improved Adaptive-Reinforcement Learning Control
      methodology for the problem of unmanned air vehicle morphing control. The
      reinforcement learning morphing control function that learns the optimal shape
      change policy is integrated with an adaptive dynamic inversion control trajectory
      tracking function. An episodic unsupervised learning simulation using the Q
      learning method is developed to replace an earlier and less accurate Actor-Critic
      algorithm. Sequential Function Approximation, a Galerkin-based scattered data
      approximation scheme, replaces a K-Nearest Neighbors (KNN) method and is used to
      generalize the learning from previously experienced quantized states and actions
      to the continuous state-action space, all of which may not have been experienced
      before. The improved method showed smaller errors and improved learning of the
      optimal shape compared to the KNN.

PMID- 18632394
TI  - Improving iris recognition performance using segmentation, quality enhancement,
      match score fusion, and indexing.
AB  - This paper proposes algorithms for iris segmentation, quality enhancement, match
      score fusion, and indexing to improve both the accuracy and the speed of iris
      recognition. A curve evolution approach is proposed to effectively segment a
      nonideal iris image using the modified Mumford-Shah functional. Different
      enhancement algorithms are concurrently applied on the segmented iris image to
      produce multiple enhanced versions of the iris image. A support-vector-machine
      based learning algorithm selects locally enhanced regions from each globally
      enhanced image and combines these good-quality regions to create a single high
      quality iris image. Two distinct features are extracted from the high-quality
      iris image. The global textural feature is extracted using the 1-D log polar
      Gabor transform, and the local topological feature is extracted using Euler
      numbers. An intelligent fusion algorithm combines the textural and topological
      matching scores to further improve the iris recognition performance and reduce
      the false rejection rate, whereas an indexing algorithm enables fast and accurate
      iris identification. The verification and identification performance of the
      proposed algorithms is validated and compared with other algorithms using the
      CASIA Version 3, ICE 2005, and UBIRIS iris databases.

PMID- 18632395
TI  - Instruction-matrix-based genetic programming.
AB  - In genetic programming (GP), evolving tree nodes separately would reduce the huge
      solution space. However, tree nodes are highly interdependent with respect to
      their fitness. In this paper, we propose a new GP framework, namely, instruction
      matrix (IM)-based GP (IMGP), to handle their interactions. IMGP maintains an IM
      to evolve tree nodes and subtrees separately. IMGP extracts program trees from an
      IM and updates the IM with the information of the extracted program trees. As the
      IM actually keeps most of the information of the schemata of GP and evolves the
      schemata directly, IMGP is effective and efficient. Our experimental results on
      benchmark problems have verified that IMGP is not only better than those of
      canonical GP in terms of the qualities of the solutions and the number of program
      evaluations, but they are also better than some of the related GP algorithms.
      IMGP can also be used to evolve programs for classification problems. The
      classifiers obtained have higher classification accuracies than four other GP
      classification algorithms on four benchmark classification problems. The testing
      errors are also comparable to or better than those obtained with well-known
      classifiers. Furthermore, an extended version, called condition matrix for rule
      learning, has been used successfully to handle multiclass classification
      problems.

PMID- 18632396
TI  - Adaptive Lyapunov-based control of a robot and mass-spring system undergoing an
      impact collision.
AB  - The control of dynamic systems that undergo an impact collision is both
      theoretically challenging and of practical importance. An appeal of studying
      systems that undergo an impact is that short-duration effects such as high
      stresses, rapid dissipation of energy, and fast acceleration and deceleration may
      be achieved from low-energy sources. However, colliding systems present a
      difficult control challenge because the equations of motion are different when
      the system suddenly transitions from a noncontact state to a contact state. In
      this paper, an adaptive nonlinear controller is designed to regulate the states
      of two dynamic systems that collide. The academic example of a planar robot
      colliding with an unactuated mass-spring system is used to represent a broader
      class of such systems. The control objective is defined as the desire to command
      a robot to collide with an unactuated system and regulate the mass to a desired
      compressed state while compensating for the unknown constant system parameters.
      Lyapunov-based methods are used to develop a continuous adaptive controller that
      yields asymptotic regulation of the mass and robot links. It is interesting to
      note that one controller is responsible for achieving the control objective when
      the robot is in free motion (i.e., decoupled from the mass-spring system), when
      the systems collide, and when the system dynamics are coupled.

PMID- 18632397
TI  - A multifaceted perspective at data analysis: a study in collaborative intelligent
      agents.
AB  - Multiagent systems are inherently associated with their distributivity, which
      enforces a great deal of communication mechanisms. To effectively arrive at
      meaningful solutions in a vast array of problem-solving tasks, it becomes
      imperative to establish a sound machinery of reconciling findings which might
      form partial solutions to an overall problem. In this paper, we focus on a broad
      category of problems of collaborative data analysis realized by a collection of
      agents having access to their individual data and exchanging findings through
      their collaboration activities. Such problems of data analysis arise in the
      context of building a global view at a certain phenomenon (process) by viewing it
      from different perspectives (and thus engaging various collections of attributes
      by various agents). Our goal is to develop some interaction between the agents so
      that they could form an overall perspective, where the knowledge available
      locally is shared and reconciled. The underlying format of knowledge built by the
      agents is that of information granules and fuzzy sets in particular. We develop a
      comprehensive optimization scheme and discuss its two-phase nature in which the
      communication phase of the granular findings intertwines with the local
      optimization being realized by the agents at the level of the individual datasite
      and exploits the evidence collected from other sites. We show how the mechanism
      of fuzzy granulation realized in the form of a well-known fuzzy c-means (FCM)
      clustering can be augmented to support collaborative activities required by the
      agents. For this purpose, we introduce augmented versions of the original
      objective function used in the FCM and derive algorithmic details. We also
      discuss an issue of optimizing the strength of collaborative linkages, so that
      the reconciled findings attain the highest level of consistency (agreement). The
      presented experimental studies include some synthetic data and selected data sets
      coming from the Machine Learning repository.

PMID- 18632398
TI  - Global synchronization control of general delayed discrete-time networks with
      stochastic coupling and disturbances.
AB  - In this paper, the synchronization control problem is considered for two coupled
      discrete-time complex networks with time delays. The network under investigation
      is quite general to reflect the reality, where the state delays are allowed to be
      time varying with given lower and upper bounds, and the stochastic disturbances
      are assumed to be Brownian motions that affect not only the network coupling but
      also the overall networks. By utilizing the Lyapunov functional method combined
      with linear matrix inequality (LMI) techniques, we obtain several sufficient
      delay-dependent conditions that ensure the coupled networks to be globally
      exponentially synchronized in the mean square. A control law is designed to
      synchronize the addressed coupled complex networks in terms of certain LMIs that
      can be readily solved using the Matlab LMI toolbox. Two numerical examples are
      presented to show the validity of our theoretical analysis results.

PMID- 18632399
TI  - Stability analysis of swarms with general topology.
AB  - This paper investigates the stability and boundary of a swarm with a general
      directed and weighted topology. The stability of a swarm is generally considered
      as cohesiveness. We construct a symmetric eigenmatrix and define an orthogonal
      eigenparameter which reflects the degree of orthogonality between the left
      eigenvector of the coupling matrix corresponding to its zero eigenvalue and the
      eigenvectors of the eigenmatrix corresponding to its nonzero eigenvalues. We
      prove that, if the topology of the underlying swarm is strongly connected, the
      swarm is then stable in the sense that all agents will globally and exponentially
      converge to a hyperellipsoid in finite time, both in open space and profiles,
      whether the center of the hyperellipsoid is moving or not. The swarm boundary and
      convergence rate are characterized by the eigenparameters of the swarm, which
      reveals the quantitative relationship between the swarming behavior and
      characteristics of the coupling topology.

PMID- 18632400
TI  - Uncertainty modeling of improved fuzzy functions with evolutionary systems.
AB  - This paper introduce a type-2 fuzzy function system for uncertainty modeling
      using evolutionary algorithms (ET2FF). The type-1 fuzzy inference systems (FISs)
      with fuzzy functions, which do not entail if ... then rule bases, have
      demonstrated better performance compared to traditional FIS. Nonetheless, the
      performance of these approaches is usually affected by their uncertain
      parameters. The proposed method implements a three-phase learning strategy to
      capture the uncertainties in fuzzy function systems induced by learning
      parameters, as well as fuzzy function structures. The improved fuzzy clustering
      initially finds hidden structures, and the genetic learning algorithm optimizes
      interval type-2 fuzzy sets to capture their optimum uncertainty interval. The
      proposed ET2FF architecture is evaluated using an extensive suite of real-life
      applications such as manufacturing process and financial market modeling. The
      results show that the proposed ET2FF method is comparable--if not superior--to
      earlier FIS in terms of generalization performance and robustness.

PMID- 18632401
TI  - Nonlinear dimensionality reduction of data lying on the multicluster manifold.
AB  - A new method, which is called decomposition-composition (D-C) method, is proposed
      for the nonlinear dimensionality reduction (NLDR) of data lying on the
      multicluster manifold. The main idea is first to decompose a given data set into
      clusters and independently calculate the low-dimensional embeddings of each
      cluster by the decomposition procedure. Based on the intercluster connections,
      the embeddings of all clusters are then composed into their proper positions and
      orientations by the composition procedure. Different from other NLDR methods for
      multicluster data, which consider associatively the intracluster and intercluster
      information, the D-C method capitalizes on the separate employment of the
      intracluster neighborhood structures and the intercluster topologies for
      effective dimensionality reduction. This, on one hand, isometrically preserves
      the rigid-body shapes of the clusters in the embedding process and, on the other
      hand, guarantees the proper locations and orientations of all clusters. The
      theoretical arguments are supported by a series of experiments performed on the
      synthetic and real-life data sets. In addition, the computational complexity of
      the proposed method is analyzed, and its efficiency is theoretically analyzed and
      experimentally demonstrated. Related strategies for automatic parameter selection
      are also examined.

PMID- 18632402
TI  - A novel gaze estimation system with one calibration point.
AB  - The design of robust and high-performance gaze-tracking systems is one of the
      most important objectives of the eye-tracking community. In general, a subject
      calibration procedure is needed to learn system parameters and be able to
      estimate the gaze direction accurately. In this paper, we attempt to determine if
      subject calibration can be eliminated. A geometric analysis of a gaze-tracking
      system is conducted to determine user calibration requirements. The eye model
      used considers the offset between optical and visual axes, the refraction of the
      cornea, and Donder's law. This paper demonstrates the minimal number of cameras,
      light sources, and user calibration points needed to solve for gaze estimation.
      The underlying geometric model is based on glint positions and pupil ellipse in
      the image, and the minimal hardware needed for this model is one camera and
      multiple light-emitting diodes. This paper proves that subject calibration is
      compulsory for correct gaze estimation and proposes a model based on a single
      point for subject calibration. The experiments carried out show that, although
      two glints and one calibration point are sufficient to perform gaze estimation
      (error approximately 1 degree), using more light sources and calibration points
      can result in lower average errors.

PMID- 18632403
TI  - Estimating object proper motion using optical flow, kinematics, and depth
      information.
AB  - For the interaction of a mobile robot with a dynamic environment, the estimation
      of object motion is desired while the robot is walking and/or turning its head.
      In this paper, we describe a system which manages this task by combining depth
      from a stereo camera and computation of the camera movement from robot kinematics
      in order to stabilize the camera images. Moving objects are detected by applying
      optical flow to the stabilized images followed by a filtering method, which
      incorporates both prior knowledge about the accuracy of the measurement and the
      uncertainties of the measurement process itself. The efficiency of this system is
      demonstrated in a dynamic real-world scenario with a walking humanoid robot.

PMID- 18632404
TI  - Exponential stability analysis for neural networks with time-varying delay.
AB  - This correspondence paper focuses on the problem of exponential stability for
      neural networks with a time-varying delay. The relationship among the time
      varying delay, its upper bound, and their difference is taken into account. As a
      result, an improved linear-matrix-inequality-based delay-dependent exponential
      stability criterion is obtained without ignoring any terms in the derivative of
      Lyapunov-Krasovskii functional. Two numerical examples are given to demonstrate
      its effectiveness.

PMID- 18632405
TI  - Fast diagnosis with sensors of uncertain quality.
AB  - This correspondence presents an approach to the detection and isolation of
      component failures in large-scale systems. In the case of sensors that report at
      rates of 1 Hz or less, the algorithm can be considered real time. The input is a
      set of observed test results from multiple sensors, and the algorithm's main task
      is to deal with sensor errors. The sensors are assumed to be of threshold test
      (pass/fail) type, but to be vulnerable to noise, in that occasionally true
      failures are missed, and likewise, there can be false alarms. These errors are
      further assumed to be independent conditioned on the system's diagnostic state.
      Their probabilities, of missed detection and of false alarm, are not known a
      priori and must be estimated (ideally along with the accuracies of these
      estimates) online, within the inference engine. Further, recognizing a practical
      concern in most real systems, a sparsely instantiated observation vector must not
      be a problem. The key ingredients to our solution include the multiple-hypothesis
      tracking philosophy to complexity management, a Beta prior distribution on the
      sensor errors, and a quickest detection overlay to detect changes in these error
      rates when the prior is violated. We provide results illustrating performance in
      terms of both computational needs and error rate, and show its application both
      as a filter (i.e., used to "clean" sensor reports) and as a standalone state
      estimator.

PMID- 18632406
TI  - Dynamic output feedback control synthesis for continuous-time T-S fuzzy systems
      via a switched fuzzy control scheme.
AB  - This correspondence paper is concerned with the problem of designing switched
      dynamic output feedback H(infinity) controllers for continuous-time Takagi-Sugeno
      (T-S) fuzzy systems. A new type of dynamic output feedback controllers, namely,
      switched dynamic parallel distributed compensation (SDPDC) controllers, is
      proposed, which are switched by basing on the values of membership functions. A
      new method for designing SDPDC controllers for guaranteeing stabilities and
      H(infinity) performances of closed-loop nonlinear systems is presented, where the
      design conditions are given in terms of the solvability of a set of linear matrix
      inequalities. It is shown that the new method provides better or at least the
      same results of the existing design methods via a pure DPDC scheme. A numerical
      example is given to illustrate the effectiveness of the proposed method.

PMID- 18632407
TI  - Binary two-dimensional PCA.
AB  - Fast training and testing procedures are crucial in biometrics recognition
      research. Conventional algorithms, e.g., principal component analysis (PCA), fail
      to efficiently work on large-scale and high-resolution image data sets. By
      incorporating merits from both two-dimensional PCA (2DPCA)-based image
      decomposition and fast numerical calculations based on Haarlike bases, this
      technical correspondence first proposes binary 2DPCA (B-2DPCA). Empirical studies
      demonstrated the advantages of B-2DPCA compared with 2DPCA and binary PCA.

PMID- 18632408
TI  - Ovarian hyperstimulation syndrome (OHSS): new strategies of prevention and
      treatment.

PMID- 18632409
TI  - Distinct differences in the induction of stimulus-mediated superoxide generation
      by polymorphonuclear neutrophils isolated from patients with different types of
      leukemia.
AB  - BACKGROUND/PURPOSE: Accumulating literature has documented that there exists a
      distinct difference in nitro blue tetrazolium reduction capacity by the
      polymorphonuclear neutrophils (PMNs) from patients with different types of
      leukemia. The underlying mechanism associated with this observed phenomenon
      remains to be clarified. METHODS: The production of O2-, monitored by a validated
      probe (lucigenin)-based ultraweak chemiluminescence, in resting and/or phorbol
      1,2-myristate-1,3-acetate (PMA)- and zymosan-stimulated systems of various
      leukemic PMNs was measured. In parallel with these studies, we also quantified
      superoxide dismutase isozymes (Cu, Zn-SOD, Mn-SOD) from these isolated PMNs by
      established methods. RESULTS: A marked increase was observed in O2- generation by
      the PMNs from patients with acute myeloid leukemia (AML), and chronic myeloid
      leukemia (CML), but not from patients with acute lymphocytic leukemia (ALL) when
      compared with controls either in the resting condition or after being stimulated
      by either PMA or zymosan. In parallel, we also quantified SOD isozyme activities
      and found that the total and CuZn-SOD of PMNs from AML were indeed significantly
      lower than either controls or ALL, implying that higher levels of O2- generation
      might result from a deficiency in this O2- metabolizing enzyme. CONCLUSION: Our
      data suggest that a distinct difference in the capability of O2- generation under
      stimulated conditions between PMNs from ALL and AML (or CML) may be of potential
      taxonomic or even therapeutic usefulness.

PMID- 18632410
TI  - Physician-scientist: attitude of graduates of clinical medicine graduate schools.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to investigate and analyze the
      motivation, results and influential factors of the research work of graduates
      from clinical medicine graduate institutes in Taiwan. METHODS: There were 679
      graduates from 1978 to 2004; all of them completed residency training following
      medical school before entering graduate study. A survey with 56 questions in four
      sections was sent to them and 268 (40%) responded. We used SPSS 11.0 for our
      statistical analysis and cross analysis. RESULTS: There were 239 (89.2%) males,
      and 29 (10.8%) females. One hundred and forty-seven (54.9%) respondents had PhD
      degrees and 98 had Master's degrees (36.5%) while 23 had both degrees (8.6%). The
      majority of respondents recognized the importance of clinical research (73.5%),
      while 25.8% thought that physicians do not necessarily have to do research. After
      graduation from medical school, 54.1% of respondents indicated that clinical
      care, teaching, and research were prioritized in that order. The graduate school
      did emphasize the importance of research, but as clinicians, clinical care was
      still the priority in their careers. A majority of the graduates thought that the
      graduate school helped to a significant degree in their research. Motivation was
      important in 83.2% to go to graduate school. The time spent in research ranged
      from 1 to 4 days a week, and the time spent each research day ranged from 1 to 6
      hours. The majority of the researchers thought that they lacked independent
      research space. For research quantity and quality, physicians with a PhD had more
      projects than those with Master's degrees in general, with 60.4% participating in
      laboratory research and 61% in clinical research. Some type of mechanism to
      reward research activities was present in 69.2% of the institutions or hospitals.
      The biggest hindrance to medical research was the lack of time for research. The
      most productive age for publishing was between 41 and 55 years. CONCLUSION: The
      physician-scientist has a unique ability to bridge the gap between
      bench/laboratory and bedside. In a changing socioeconomic climate as well as
      cultural evolution in medical practice, external pressures are unavoidable. The
      support of research from institutions or government is very important, as are
      financial resources, space and equipment. For those physicians who are going into
      research, a special training of strict methodology in research will obviously
      become necessary.

PMID- 18632411
TI  - Relationship between age at menarche and skeletal maturation stages in Taiwanese
      female orthodontic patients.
AB  - BACKGROUND/PURPOSE: The age at menarche reflects a pubertal girl's physiologic
      maturity. The aims of this study were to evaluate the relationship between the
      age at menarche and skeletal maturation in female orthodontic patients. METHODS:
      Hand-wrist radiographs and lateral cephalometric radiographs from 304 adolescent
      female subjects (age, 8-18.9 years) were selected from the files of the
      Department of Orthodontics, National Taiwan University Hospital (NTUH). Hand
      wrist bone maturation stages were assessed using the NTUH Skeletal Maturation
      Index (NTUH-SMI). Cervical vertebral maturation stages (CVMS) were determined
      using the latest CVMS Index. Menarcheal ages were self-reported by the patients
      and verified by the patients' mothers. The relationships between the NTUH-SMI or
      CVM stages and menarcheal status were investigated. RESULTS: More than 90% of the
      148 subjects who had already attained menstruation had skeletal maturation beyond
      the NTUH-SMI stage four or CVMS III. However, the subjects who had never
      experienced menarche mostly had skeletal maturation before NTUH-SMI stage five or
      CVMS IV. During the period of orthodontic treatment, 19 females experienced their
      menarche. The mean age at menarche for the 167 female patients in total was 11.97
      years. In average, menarche occurred between NTUH-SMI stages four and five or
      between CVM stages III and IV. The percentage of girls with menses increased from
      1.2% at age 9 to 6.6% at age 10, 39.5% at age 11, 81.4% at age 12, 97% at age 13,
      and 100% at age 14. Compared with the results obtained 20 years previously, we
      found a downward shift of 0.47 years per decade for the mean age at menarche in
      female orthodontic patients. CONCLUSION: The majority of female orthodontic
      patients have passed the pubertal growth spurt when they experience their
      menarche. Menarche usually follows the pubertal growth spurt by about 1 year and
      occurs after NTUH-SMI stage four or CVMS III.

PMID- 18632412
TI  - Favorable results of concomitant tacrolimus and sirolimus therapy in Taiwanese
      renal transplant recipients at 12 months.
AB  - BACKGROUND/PURPOSE: Combined therapy of sirolimus and cyclosporine has been found
      to exacerbate cyclosporine-related nephrotoxicity and to imperil graft renal
      function. We hypothesized that tacrolimus could bring about better renal function
      than cyclosporine when used in combination with sirolimus and corticosteroids for
      de novo renal transplantation. METHODS: A two-arm randomized study was conducted
      to test the hypothesis. Patients who gave written informed consent and received
      renal transplantation were randomized to take sirolimus in combination with
      either tacrolimus or cyclosporine. The primary endpoint of this study was renal
      function, and the secondary endpoints were acute rejection, graft and patient
      survival, metabolic side effects and infectious complications. RESULTS: A total
      of 41 Taiwanese renal transplant patients were randomized to receive cyclosporine
      (CsA group, n = 20) or tacrolimus (TAC group, n = 21) in combination with
      sirolimus and corticosteroids. The average estimated glomerular filtration rate
      (eGFR) was 52.77 +/- 3.86 mL per minute for the TAC group at 6 months, and 46.42
      +/- 3.95 mL per minute for the CsA group (p > 0.05). At 12 months, the average
      eGFR was 52.04 +/- 4.38 mL per minute for the TAC group, and 46.79 +/- 4.38 mL
      per minute for the CsA group (p > 0.05). The biopsy-proven acute rejection rate
      of the TAC group was 4.76% (1/21), and that of the CsA group was 5.00% (1/20) at
      12 months. The 12-month graft survival rates for the TAC and CsA groups were 100%
      and 90% (p = 0.142), respectively. CONCLUSION: Our study demonstrated that
      concomitant tacrolimus and sirolimus therapy resulted in a favorable outcome in
      Taiwanese renal transplant patients at 12 months. Large-scale clinical trials
      will be needed to further address the issue of which calcineurin inhibitor,
      cyclosporine or tacrolimus, provides better renal function and graft survival for
      renal transplant patients.

PMID- 18632413
TI  - Reducing limping by tibial lengthening along nails in adult unilateral
      developmental dysplasia of the hip with high dislocation.
AB  - BACKGROUND/PURPOSE: Treatment of adult neglected developmental dysplasia of the
      hip (DDH) with high dislocation is still not established. The main concern of
      young patients is leg-length discrepancy (LLD), which leads to limping gait and
      impaired body image. Such patients usually ask for a minimally invasive treatment
      that can improve the LLD. METHODS: Between 1993 and 2003, 17 patients with
      neglected DDH with high dislocation (mean age, 22.8 years) were treated by tibial
      lengthening using the Ilizarov external fixator over an intramedullary nail. The
      inclusion criteria were unmarried young adults, unilateral lesion, significant
      limping or unsightly gait with psychologic discomfort, marked shortening > 4 cm
      with the block test, and benefit from a shoe-lift. Exclusion criteria were
      patients older than 30 years, hip pain as the chief complaint, and compensated
      low hip dislocation without significant limping. RESULTS: All 17 patients had
      eventual bone consolidation without further operation. The mean external fixation
      index was 14.2 day/cm. Bone formation was good in all patients with a mean
      consolidation index of 57.7 day/cm. At an average follow-up period of 7.8 years,
      the limping was much improved from a moderate or severe degree to a mild degree
      in all patients. No patients had equinus contracture. All patients were satisfied
      with their treatment results. There were two complications: transient loss of big
      toe extension and mild wound infection. CONCLUSION: Tibial lengthening can
      improve limping in adult patients with neglected DDH and high dislocation with a
      low morbidity. Lengthening along intramedullary nails can effectively reduce the
      external fixation time, improve bone formation, and prevent complications.

PMID- 18632414
TI  - Arrhythmogenic right ventricular dysplasia: clinical characteristics and
      identification of novel desmosome gene mutations.
AB  - BACKGROUND/PURPOSE: Desmosome gene mutations have been reported in patients with
      arrhythmogenic right ventricular dysplasia (ARVD). However, there are hardly any
      genetic studies in Asians. We studied the clinical characteristics, cardiac
      manifestations and desmosome gene mutations in ARVD patients in Taiwan. METHODS:
      Medical records of five ARVD patients were reviewed and genomic DNA was obtained
      from peripheral blood samples. Mutation screening in desmoplakin (DSP),
      plakophilin-2, desmoglein-2 (DSG2) and desmocollin-2 genes was performed using
      polymerase chain reaction and DNA sequencing techniques. RESULTS: Among the five
      patients, three presented with palpitations followed by loss of consciousness,
      and the other two had palpitations or chest tightness without loss of
      consciousness. Electrocardiogram (ECG), magnetic resonance imaging and signal
      averaged ECG results were similar to those reported in Western countries.
      Mutations in the desmosome genes were identified in four of the five patients
      (three with a DSG2 mutation and one with a DSP mutation). Five gene mutations
      were noted in four patients and all mutations were novel (one patient had a DSG2
      double mutation). The mutation types were missense in four and splicing mutation
      in one. CONCLUSION: Patients with ARVD in Taiwan had similar clinical and cardiac
      manifestations as reported in the Western literature. More than half of the
      patients had desmosome gene mutations.

PMID- 18632415
TI  - Confocal microscopy study of neurovascular distribution in facial port wine
      stains (capillary malformation).
AB  - BACKGROUND/PURPOSE: Vascular ectasia observed in port wine stain (PWS) birthmarks
      might be secondary to localized reduction of neural innervation and associated
      loss of autonomic stimulation. Our objective was to investigate this theory and
      evaluate nerve density, blood vessel density, and average blood vessel size in
      untreated and pulsed dye laser with cryogen spray cooling (PDL-CSC) treated PWS
      skin. METHODS: Biopsy skin specimens were taken from 14 adults with a PWS,
      categorized by: uninvolved skin; untreated PWS skin; PWS skin with a history of
      good blanching, and PWS skin with a history of poor blanching both in response to
      PDL treatment. Seven specimens of normal, unaffected skin were used as the
      experimental control group. Indirect immunohistochemistry was performed on all
      specimens followed by confocal microscopy imaging with computer analysis to
      determine nerve density, blood vessel density, and average blood vessel size.
      RESULTS: Nerve density was significantly decreased in all PWS sites as compared
      to uninvolved skin (p < 0.01). Average blood vessel diameter was larger in
      untreated as compared to treated PWS sites and varied between different sites
      within a single PWS. CONCLUSION: Nerve density was decreased in all evaluated PWS
      sites, and this may be a factor in lesion pathogenesis. PWS blood vessel size
      correlated with the PDL blanching response and may prove to be a useful
      prognostic indicator of therapeutic outcome.

PMID- 18632416
TI  - Unilateral thalamic hypometabolism in patients with temporal lobe epilepsy.
AB  - BACKGROUND/PURPOSE: Interictal brain 18F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET) is useful for localizing the focus of a seizure, and
      thalamic hypometabolism has been observed in temporal lobe epilepsy (TLE). In
      this study, we aimed to investigate the prevalence of thalamic hypometabolism and
      to assess the usefulness of this supplementary finding for lateralizing epileptic
      foci on FDGPET scans in patients with TLE. METHODS: This was a retrospective
      study of 47 patients who underwent anterior temporal lobectomy to treat medically
      intractable TLE. Other inclusion criteria were age older than 18 years,
      preoperative interictal FDG-PET, no structural abnormality (except for mesial
      temporal sclerosis) on preoperative magnetic resonance imaging, and seizure-free
      status (Engel class I) for at least 2 years after the operation. The presence and
      location of hypometabolism on FDG-PET scans were recorded. RESULTS: Of the 47
      patients examined, 12 were subsequently excluded. Concomitant hypometabolism in
      both the temporal lobe and the ipsilateral thalamus was observed on FDG-PET scans
      in seven (20%) of the remaining 35 patients. One patient had thalamic
      hypometabolism contralateral to the hypometabolic temporal lobe. CONCLUSION:
      Ipsilateral thalamic hypometabolism is a supplementary finding on FDG-PET scans
      in patients with TLE and can aid in lateralizing epileptic foci during FDG-PET.
      However, in rare cases, hypometabolism of the contralateral thalamus can occur
      and cause false lateralization.

PMID- 18632417
TI  - Clinical characteristics of MuSK antibody-positive myasthenia gravis in Taiwan.
AB  - Circulating antibodies of the acetylcholine receptor (AchRAb) are detectable in
      most patients with generalized myasthenia gravis (MG). A newly discovered
      antibody against muscle-specific kinase (MuSKAb) has been detected in 40-70% of
      AchRAb-negative MG patients. We report a series of Taiwanese MuSKAb-positive
      patients, and compare their clinical features with MuSKAb-negative patients and
      also with MuSKAb-positive Caucasians. Five out of 44 seronegative generalized MG
      patients (11.4%) were positive for MuSKAb. Patients with MuSKAb tended to have
      severe disability and bulbar involvement, and more often experienced crisis or
      impending crisis. Although all of these patients showed an initial response to
      immunosuppressant therapy, they had greater disability at follow-up. The clinical
      features of Taiwanese MuSKAb-positive patients were not different from those of
      Caucasians, except for a lower prevalence.

PMID- 18632418
TI  - Neurocysticercosis presenting with epilepsia partialis continua: a
      clinicopathologic report and literature review.
AB  - Neurocysticercosis, a disease caused by a tapeworm larva in the central nervous
      system, is the leading cause of acquired epilepsy in undeveloped regions of the
      world. In Taiwan, after improvements in sanitation, tapeworm infection became
      very rare except in mountain areas inhibited by aborigines. However, in recent
      years, immigration from other Asian countries has increased rapidly, and parasite
      infection of the central nervous system may again become an important cause of
      adult-onset epilepsy in clinical practice. Here, we describe a 27-year-old female
      Thai immigrant who presented with adult-onset epilepsia partialis continua of the
      right upper extremity. Electroencephalography showed epileptiform discharge in
      the left central region, while brain magnetic resonance imaging showed a small
      enhanced lesion in the left premotor cortex. She underwent operation and
      pathology of the mass revealed a degenerated cysticercus. In this article, we
      provide detailed neuroimaging findings, pathologic report, and literature review
      of this parasitic infection of the central nervous system. This case calls for
      physicians to be aware of cysticercosis as an etiology of adult-onset epilepsy in
      immigrants from endemic countries.

PMID- 18632419
TI  - Osteoid osteoma of phalangeal bone.
AB  - Osteoid osteoma involving the phalanges of the fingers and toes are rare in the
      literature. We report two patients who were successfully treated with surgery.
      The first case was an 18-year-old male with osteoid osteoma of the left ring
      finger who presented with marked tenderness and swelling of the finger pulp of 2
      years' duration. He underwent surgical excision with complete relief of the
      symptoms. No complications were observed over a follow-up period of 5 years. The
      second case was a 38-year-old male with painful enlargement and clubbing
      involving the distal phalanx of the right fourth toe which subsided gradually
      after surgical excision. No malignant change or recurrence was found and the
      patient remained free of symptoms 11 years after the operation. We conclude that
      complete surgical excision is the treatment of choice in small phalangeal bones
      where the tumors are readily accessible.

PMID- 18632420
TI  - Cellular and molecular mechanisms underlying bone marrow and liver fibrosis: a
      review.
AB  - Chronic fibroproliferative diseases are an important cause of morbidity and
      mortality in the world. Fibrotic diseases occur in a large variety of vital
      organs, and the process of fibrosis seems common to all tissues. In all of
      fibrotic reactions, the underlying cellular and molecular mechanisms involve
      leukocyte infiltration, the persistence of inflammation in the tissue, and the
      proliferation of cells with a myofibroblast phenotype. The different cell types
      participating to this process sustain production of growth factors, proteolytic
      enzymes, angiogenic factors, and fibrogenic cytokines, which together stimulate
      the deposition of connective tissue elements that progressively destroy and
      remodel normal tissue architecture. This review focuses on the comparison of two,
      major, chronic fibroproliferative diseases: the myelofibrosis which develops in
      bone marrow, a "fluid" tissue producing circulating haematopoietic cells, and
      liver fibrosis, which demonstrates all the features of solid tissue damage. We
      discuss the etiology and histological quantification of each type of fibrosis,
      the implication of cell partners, cytokines and growth factors, animal models
      developed to study fibrosis, and antifibrotic therapies for each of these two
      fibroproliferative disease models.

PMID- 18632421
TI  - Rank ligand stimulation induces a partial but functional maturation of human
      monocyte-derived dendritic cells.
AB  - Mature dendritic cells (DC) are efficient, antigen-presenting cells required for
      the stimulation of naive T lymphocytes. Many members of the tumour necrosis
      factor (TNF) receptor family are involved in DC maturation, such as Fas, CD40,
      OX40L, LIGHT (homologous to lymphotoxins, exhibits inducible expression, and
      competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a
      receptor expressed by T lymphocytes) or RANK (receptor activator of NFkappaB),
      with different, but often overlapping effects. We focused our attention on RANK
      DC stimulation, since RANK ligand (RL) is expressed on activated T lymphocytes
      with different kinetic and expression patterns from the other members of TNF
      family previously cited. After culture with RL-transfected cells, a significant
      percentage of immature DC generated from monocytes (Mo-DC) acquired a typical,
      mature DC morphology and phenotype characterised by up-regulation of CD83, DC
      LAMP (lysosome-associated membrane glycoprotein), HLA class I, CD86 and CD54. The
      functional RL-mediated maturation was demonstrated by a decrease in DC
      macropinocytosis and acquisition of the capacity to stimulate allogenic T-cells.
      Among the various cytokines tested, we detected only a weak up-regulation of IL
      12p40. Our results show that ligation of RANK on DC cell surfaces is not only a
      survival stimulus, but also induces a partial and specific mature DC phenotype,
      the physiological significance of which is under investigation.

PMID- 18632422
TI  - Increased concentration of platelet-derived chemokines in serum of patients with
      delayed pressure urticaria.
AB  - BACKGROUND: Delayed pressure urticaria (DPU) is a distinct form of urticaria,
      characterized by marked dermal swelling, deep inflammatory infiltrate and
      systemic symptoms. Little is known about inflammatory mediators involved in this
      disease. OBJECTIVE: To investigate secretion of platelet-specific chemokines,
      platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG) during the course of
      DPU. METHODS AND MATERIAL: Plasma concentrations of PF-4 and beta-TG were
      measured in eight adult DPU patients and in 15, age- and sex-matched, healthy
      controls. RESULTS: Plasma PF-4 and beta-TG concentration scores were
      significantly higher in the DPU group as compared with the control subjects.
      CONCLUSION: The present study, as well as an earlier contribution, suggest that
      distinct platelet activity may be identified in different types of urticaria. In
      contrast to chronic idiopathic urticaria, chronic urticaria with a positive
      response to autologous serum skin testing, and acute urticaria, delayed pressure
      urticaria may be associated with increased secretion of platelet chemokines,
      similar to that observed in cold urticaria.

PMID- 18632423
TI  - Cytokine response following transthoracic and transhiatal esophagectomy in
      patients with esophageal cancer.
AB  - Curative esophageal resection is usually performed using either a transthoracic
      (TT) or transhiatal (TH) approach. Forty patients with esophageal squamous cell
      carcinoma who underwent esophagectomies (24 TT and 16 TH), 12 patients who
      underwent surgery for gastric cancer, and 16 healthy individuals were enrolled in
      this study. Blood samples were taken from the patients, pre- and post-surgery.
      The levels of synthesis of T-helper 1 and 2 cytokines were assessed in vitro in
      the presence of mitogen. Our initial data indicated that at admission, 24 h
      before surgery, blood cells from both groups of esophageal cancer patients
      produced significantly lower levels of the Th1 cytokines, IFN-gamma and IL-2 than
      those from cells of healthy donors. Cells collected from gastric cancer patients
      prior to surgery produced intermediate levels of IFN-gamma and IL-2:
      significantly lower than healthy donors, and slightly more (non-significant) than
      esophageal cancer patients. These results contrast with those for the production
      of Th2 cytokines prior to surgery, which did not differ significantly between any
      groups: either the esophageal or gastric cancer patients, or healthy donors. Th1
      and Th2 cytokine production was then studied using blood cells collected seven
      days after surgery. Cells from both groups of esophageal cancer patients,
      undergoing either TT or TH surgery, produced significantly lower levels of the
      Th1 cytokines, IFN-gamma and IL-2 than those from cells of gastric cancer
      patients who had undergone surgery. Postoperative and preoperative production was
      compared. For patients who had undergone TT esophageal resection, we observed
      that the post-operative production of IL-2, IL-5 and IL-13 was significantly
      lower than the pre-operative production of those cytokines. Such reduced post
      operative compared to pre-operative production was only significant in patients
      who had undergone TT esophagectomy. A similar, but non-significant trend was
      observed in patients who had undergone either TH esophagectomy, or gastrectomy.
      The results indicate that digestive tract cancer patients, both esophageal and
      gastric, have (prior to surgery), a significantly reduced, basal, mitogen-induced
      production of Th1 but not of Th2 cytokine. Post-operatively, a significantly
      reduced production of Th1 and Th2 cytokines, except for IFN-gamma, was observed
      only in patients who had undergone surgical esophageal resection using the TT
      method.

PMID- 18632424
TI  - Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF
      alpha, in cardio-pulmonary bypass.
AB  - BACKGROUND: While statins are increasingly used in cardiopulmonary bypass (CPB),
      the anti-inflammatory effects of individual statins, within the context of
      various treatment regimes, need further examination. The present study evaluates
      the anti-inflammatory effectiveness of the short-term, preoperative and intensive
      postoperative use of pravastatin in CPB. METHOD: Forty three patients undergoing
      CPB were enrolled in a randomized, prospective clinical study. One group (n =
      21), received pravastatin, the other (n = 22) did not. Patients in the
      pravastatin group received one dose of 40 mg per day for nine days, starting 48
      hours before CPB, with an additional dose of 40 mg one hour after surgery. Plasma
      levels of selected inflammatory mediators were measured at baseline and tracked
      systematically. RESULTS: Pravastatin reduced postoperative interleukin-6 (IL-6)
      levels significantly at 24 and 48 hours, and at seven days. Mean +/- SD values,
      for treated versus untreated patients were: at 24 hours, 159.5 +/- 58.5 versus
      251.2 +/- 53.0 pg/mL (p < 0.001); at 48 hours, 81.9 +/- 31.5 versus 194.2 +/-
      56.3 pg/mL (p < 0.001); and at seven days, 16.4 +/- 7.2 versus 30.8 +/- 12.6 (p <
      0.001). C-reactive protein (CRP) decreased significantly on the seventh
      postoperative day, when plasma levels were 3.6 +/- 1.1 in the treated patients
      versus 8.2 +/- 2.1 mg/dL in the controls (p < 0.001). No changes in plasma IL-1
      and TNF-alpha were found during entire study. CONCLUSIONS: Pravastatin induced a
      precocious modulation of IL-6 expression and a later reduction of plasma CRP
      levels. Pravastatin;s effects on the expression of these pivotal inflammatory
      mediators strongly support its well-timed use in CPB.

PMID- 18632426
TI  - Year three of supportive cancer therapy.

PMID- 18632427
TI  - Highlights from: The 9th International Congress on Hematologic Malignancies,
      Whistler, BC, Canada.

PMID- 18632425
TI  - Cytokine single nucleotide polymorphisms in Iranian populations.
AB  - Cytokines are important immunomodulatory molecules involved in immune responses
      against microorganisms; they also have an important role in the setting of immune
      system disorders. Cytokine single nucleotide polymorphisms have been extensively
      studied in different, normal populations as well as in association with disease.
      Cytokine gene polymorphisms are potentially important as genetic predictors of
      disease susceptibility, clinical outcome, and as a tool for anthropological
      studies. In this study, samples have been collected from 455 healthy individuals
      located in different regions of Iran (Tehran, Yazd, Sistan and Balochistan).
      Allele and genotype frequencies of cytokine SNP, including: IL-1alpha, IL-1beta,
      IL-1R, IL-1RA, IL-2, IL-4, IL-4RA, IL-6, IL-10, IL-12, TNF-alpha, TGF-beta and
      IFN-gamma were investigated, using the PCR-SSP method. Allele frequencies in
      Tehran and Yazd populations were similar, except for TGF-beta. Allele frequencies
      in Sistani & Baloch populations were similar at all positions, except for IL
      1beta at position of -511 and IFN-gamma genes at position UTR5644; there were
      some differences in allele frequencies comparing these populations with the Yazd
      population, including: IL-4, IL-6, IL-10, TGF-beta and TNF-alpha. Although some
      significant differences were observed for some cytokines, it seems that the
      cytokine gene polymorphism profile of the Iranian population is similar to that
      of Caucasians, particularly the Italian population.

PMID- 18632428
TI  - Therapeutic use of the cannabinoid receptor antagonist rimonabant in weight loss
      and smoking cessation.

PMID- 18632429
TI  - Denosumab (AMG 162), a Fully Human Monoclonal Antibody Against RANK Ligand
      Activity.

PMID- 18632430
TI  - Every-three-week erythropoietic support during chemotherapy for cancer: current
      status and future issues.
AB  - Recently, it has been demonstrated that the administration of chemotherapy alters
      the pharmacology of erythropoietic-stimulating proteins (ESPs), such as
      endogenous erythropoietin and darbepoetin alfa, with an apparent decrease in
      clearance and substantial prolongation of half-life. This observation, coupled
      with the popularity of every-3-week chemotherapy regimens, makes it logical to
      pursue less-frequent dosing schedules for darbepoetin alfa. Two published studies
      have demonstrated that darbepoeitin alfa administered at a dose of 6.75 mug/kg or
      every 3 weeks to anemic patients with cancer is associated with improvements in
      hemoglobin levels. It has also been shown that dosing on the same day as
      chemotherapy is as efficacious and safe as dosing asynchronously in patients
      receiving every-3-week chemotherapy. These studies have increased our
      understanding of the biology of the interplay between chemotherapy,
      erythropoiesis, and ESPs and should facilitate the development of increasingly
      convenient and effective approaches to the treatment of chemotherapy-associated
      anemia. These insights are reviewed in this article. At the same time, evidence
      is accumulating that earlier initiation of ESP therapy, before severe anemia and
      symptoms occur, will be associated with further reduction in transfusion
      requirements, less patient-reported fatigue, and lower required doses of ESPs. In
      addition, recently presented trials have reported very important improvements in
      erythropoietic response to ESPs when patients with chemotherapy-associated anemia
      are treated with parenteral iron. The early initiation and parenteral iron
      initiatives pose opportunities and challenges for treatment regimens emerging
      from our increasing biologic understanding, and these are also reviewed.

PMID- 18632431
TI  - Kyphoplasty and vertebroplasty for the treatment of spinal metastases.
AB  - Advances in the detection and treatment of many cancers have led to prolonged
      life and improved quality of life for patients with localized and metastatic
      cancer; however, the improved survival of patients with osseous lesions, coupled
      with the destructive nature of metastatic disease and the medications to treat
      these lesions, has increased the likelihood of vertebral body collapse.
      Conventional surgical techniques are often poorly tolerated by this patient
      population, whereas nonoperative management can lead to continued pain and
      diminished function in the terminal years of life. Vertebroplasty and kyphoplasty
      are minimally invasive vertebral augmentation techniques used to treat pain in
      such patients while maintaining a positive safety profile. Vertebroplasty and
      kyphoplasty are tools in a spectrum of treatments for vertebral compression
      fractures secondary to osteoporosis and metastatic disease and are not mutually
      exclusive. Additional research in this area in large cohorts of patients is
      needed to establish these techniques as safe and clinically cost-effective
      methods of treating patients with vertebral compression fractures secondary to
      spinal metastases.

PMID- 18632432
TI  - Vertebroplasty versus kyphoplasty in the cancer setting: rethinking the relative
      indications.

PMID- 18632433
TI  - Venous thromboembolism in patients with cancer and its relationship to the
      coagulation cascade and vascular endothelial growth factor.
AB  - Venous thromboembolism (VTE) is a well-recognized problem in malignancy. Patients
      with cancer who have VTE have a worse prognosis than other patients with cancer.
      Hypercoagulability in patients with cancer is related to malignancy itself and
      its treatment. These patients have multiple risk factors for thromboembolism,
      such as being immobilized, having central venous catheters, and receiving
      chemoradiation therapy. Cancer procoagulant, tissue factor, factor VIII, and
      thrombin have important roles in causing cancer-associated thromboembolism.
      Tumors require neovascularization for delivering oxygen and other nutrients.
      Therefore, angiogenesis facilitates tumor growth, invasion, and metastasis. New
      blood vessels formed by angiogenesis are thrombogenic. Hypercoagulability and
      tumor growth are closely related. Vascular endothelial growth factor (VEGF) is a
      proangiogenic factor that may also cause VTE in patients with cancer. The
      relationship between cancer, angiogenesis, VEGF, and thrombosis is reviewed
      herein. Studies are ongoing to enhance our understanding of this complex
      interaction.

PMID- 18632434
TI  - Relationship between venous thromboembolism and vascular endothelial growth
      factor in cancer.

PMID- 18632435
TI  - Final results of a placebo-controlled study of filgrastim in small-cell lung
      cancer: exploration of risk factors for febrile neutropenia.
AB  - BACKGROUND: A phase III study of filgrastim as an adjunct to combination
      chemotherapy in previously untreated patients with limited- or extensive-stage
      small-cell lung cancer was conducted. This final analysis explores baseline
      factors that might predict febrile neutropenia and also reports the results of
      463 open-label filgrastim cycles that were delivered after patients' initial
      episode of the primary endpoint, ie, febrile neutropenia. PATIENTS AND METHODS: A
      total of 244 patients were randomized to receive placebo or filgrastim in </= 6
      cycles of chemotherapy (cyclophosphamide/doxorubicin/etoposide). RESULTS: The
      cumulative percent of patients receiving filgrastim who experienced febrile
      neutropenia was approximately 50% lower than those given placebo (38% vs. 74%,
      respectively; P < 0.0001). Significant treatment-related reductions were also
      seen in the incidence and duration of grade 4 neutropenia. Cycle 1 displayed the
      highest incidence of neutropenia with or without fever and the longest duration
      of neutropenia relative to later cycles. Patients crossing over to open-label
      filgrastim from their blinded treatment assignment displayed event rates similar
      to those in the blinded filgrastim group. Patients who experienced febrile
      neutropenia in cycle 1 were at a significantly higher risk for subsequent events
      compared with those who were event-free in cycle 1. Women displayed a higher risk
      for febrile neutropenia than men, but no other baseline risk factors were
      detected. CONCLUSION: Given the high rate of febrile neutropenia in cycle 1 and
      the higher risk for subsequent events in patients with a cycle 1 event, we
      conclude that growth factor administration starting in cycle 1 should be
      considered for patients receiving moderately to highly myelosuppressive
      chemotherapy regimens.

PMID- 18632436
TI  - A pilot study to evaluate the safety and clinical outcomes of once-weekly epoetin
      alfa 80,000 u in anemic patients with cancer receiving chemotherapy.
AB  - BACKGROUND: Epoetin alfa is indicated for the treatment of chemotherapy-induced
      anemia at doses of 150 U/kg 3 times weekly or 40,000 U once weekly. Higher
      starting doses may lead to higher hematologic response rates (RRs), earlier
      hematologic responses, and earlier identification of nonresponders. The
      hematologic response and safety of epoetin alfa at a starting dose of 80,000 U
      once weekly in anemic patients (hemoglobin [Hb] </= 11 g/dL) with nonmyeloid
      malignancies receiving chemotherapy were evaluated in this open-label,
      multicenter pilot study. PATIENTS AND METHODS: Epoetin alfa was initiated at
      80,000 U once weekly and reduced if Hb increased to > 13 g/dL or increased > 1.3
      g/dL in a 2-week period during the 12-week study. The primary efficacy endpoint
      was major hematologic response (Hb increase >/= 2 g/dL or Hb >/=12 g/dL,
      independent of transfusion). Secondary endpoints were minor hematologic response
      (Hb increase >/= 1 g/dL but > 2 g/dL) and incidence of transfusions. RESULTS: Of
      69 patients enrolled, 47 (68%) completed the study. A majority of patients (72%)
      exhibited a major hematologic response with epoetin alfa 80,000 U once weekly.
      Mean Hb levels increased by 2.2 g/dL from baseline after 12 weeks of therapy. Six
      patients (8.8%) received packed red blood cell transfusions during the study. The
      dose of epoetin alfa was reduced, or held then reduced, per protocol in 48
      patients (69.6%). Ten patients (14.5%) in the safety population experienced a
      total of 11 clinically relevant thrombotic vascular events. CONCLUSION: Epoetin
      alfa at a starting dose of 80,000 U once weekly (with appropriate dose
      reductions) increased Hb level, was associated with a packed red blood cell
      transfusion rate > 5% after 4 weeks of therapy, and was safe and generally well
      tolerated in anemic patients with cancer receiving chemotherapy. The hematologic
      RR, however, was not markedly improved compared with previous trials with 40,000
      60,000 U once weekly, perhaps partly because of the high frequency of dose
      reductions.

PMID- 18632437
TI  - Level of Concordance Between Proxy and Cancer Patient Ratings in Brief
      PainInventory.
AB  - BACKGROUND: The objective of this study was to assess whether caregivers serve as
      valid and reliable proxies for the assessment of a patient's pain level using the
      Brief Pain Inventory (BPI) assessment tool. PATIENTS AND METHODS: Twenty-seven
      patients with cancer with pain, referred for health care management to the
      Toronto Sunnybrook Regional Cancer Centre and the Sunnybrook and Women's College
      Health Sciences Centre, and their proxies participated in this study. Patient and
      proxy completed the BPI independently, with proxies given explicit instructions
      to rate and answer the questions from the perspective of the patient. Patient and
      proxy also completed a data extraction form to obtain patient/proxy
      characteristics such as sex, age, primary cancer site, and relationship. An
      intraclass correlation coefficient (ICC) was performed for each question of the
      BPI. RESULTS: In this study, we found poor to good agreement for questions that
      are subjective (eg, average pain), whereas the highest agreement was for worst
      pain scoring (ICC = 0.72). Poor to moderate agreement was found for questions
      that are objective (eg, walking ability), suggesting that the functional
      interference questions of the BPI may be too vague for proxies to respond
      reliably. CONCLUSION: The findings indicate that proxies and patients agree well
      on worst pain levels but agree much less on the effectiveness of pain medications
      and patients' average level of pain. Further investigations should examine other
      tools for pain assessment that may be more reliably used by a proxy.

PMID- 18632438
TI  - Targeting and palliating malignant ascites: an overview of an upcoming clinical
      trial from the north central cancer treatment group.

PMID- 18632439
TI  - A correction: meeting highlights from the april 2005 issue of supportive cancer
      therapy.

PMID- 18632440
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18632441
TI  - Integrating support into cancer therapy.

PMID- 18632442
TI  - The Role of Plerixafor (AMD3100) in Mobilizing Hematopoietic Progenitor Cells in
      Patients with Hematologic Malignancies.

PMID- 18632443
TI  - The risk of cumulative renal effects of intravenous bisphosphonates.
AB  - Some level of renal dysfunction is common in patients with cancer. This could be
      a result of an age-related kidney function decrease, the underlying disease (eg,
      multiple myeloma), or the effects of nephrotoxic medications. Some intravenous
      (I.V.) bisphosphonates have been associated with occasional renal toxicity in the
      clinical setting. Therefore, the choice of an I.V. bisphosphonate should take
      into account the risk of renal deterioration. Preclinical studies also suggest
      that there might be considerable differences between the renal safety profiles of
      commonly used I.V. bisphosphonates. Variations in the risk of histopathologic
      damage and the ability to cause cumulative toxicity have been observed in
      comparative preclinical studies of I.V. bisphosphonates. The reasons for these
      apparent differences are not fully understood. Research shows that renal safety
      profiles might be influenced by pharmacokinetic properties, such as renal tissue
      half-life, protein binding, and intracellular potency. Preclinical analyses are
      warranted in order to confirm and evaluate these differences between
      bisphosphonates.

PMID- 18632444
TI  - Group medical appointments: organization and implementation in the bone marrow
      transplantation clinic.
AB  - Group medical appointments provide patients with prompt access to care, greater
      attention to their psychosocial needs, and increased time with their medical
      team. Care providers evaluate more patients with similar needs in a shorter
      period. Eligible patients (between 100 days and 3 years after autologous stem
      cell transplantation) were contacted to participate. The laboratory and
      radiographic results of each patient's completed reevaluation were entered into
      the electronic template office note before their visit. A group medical visit
      model, called a Physical Shared Medical Appointment (PSMA), was employed because
      this uses individual patient examinations followed by a group meeting. On the day
      of the visit, brief physical examinations were performed on each patient. A
      transplantation physician then met with the group of patients and answered
      questions. Patient satisfaction surveys were distributed upon completion of the
      group session. Each PSMA was limited to 10 patients to facilitate patient
      participation. Questions during the group meeting were general and applicable to
      all patients. At completion of the 2-hour visit, patient surveys indicated an
      extremely high level of satisfaction and the preference to attend a future PSMA.
      Issues discussed during the group meeting were pertinent to all transplant
      recipients, regardless of diagnosis. The PSMA model allows the patient to spend
      extended time with their care providers while providing the care providers an
      opportunity to discuss health issues with numerous patients during 1 appointment.
      The Dartmouth Transplant PSMA model is expanding to pretransplantation and
      postallogeneic transplant recipients.

PMID- 18632445
TI  - Dehydroepiandrosterone for the treatment of hot flashes: a pilot study.
AB  - BACKGROUND: Published data regarding the negative risk-benefit ratio of
      traditional estrogen/progesterone hormone replacement therapy for menopausal
      symptoms have indicated the need for alternative treatments. Dietary supplements
      and herbal products are popularly used for menopausal control without a large
      evidence base. Therefore, a prospective pilot trial using 50 mg of
      dehydroepiandrosterone (DHEA) once daily for 4 weeks following a baseline week
      was developed to explore whether DHEA has any efficacy in reducing hot flashes.
      Safety issues were also evaluated. PATIENTS AND METHODS: Twenty-eight women were
      enrolled in this study, 22 of whom are evaluable. The primary outcome was the
      reduction in hot flash score (frequency multiplied by average severity) from
      baseline as measured by validated self-report daily hot flash diaries. RESULTS:
      The mean hot flash score decreased 50% from baseline, and there were no side
      effects that were significantly worse compared with baseline. Quality of life
      related to hot flashes showed statistically significant improvement after 4 weeks
      of DHEA therapy. CONCLUSION: This pilot study provides data supporting the
      hypothesis that DHEA is well tolerated and can reduce hot flashes.
      Dehydroepiandrosterone should be studied further in a larger, placebo-controlled
      trial.

PMID- 18632446
TI  - Factor v leiden mutation in patients with breast cancer with a central venous
      catheter: risk of deep vein thrombosis.
AB  - BACKGROUND: The objective of this study was to analyze the influence of the
      prothrombotic factor V Leiden (FVL) and G20210A prothrombin mutations on the
      frequency of the first episode of catheter-related deep vein thrombosis (DVT) in
      a cohort of patients with locally advanced or metastatic breast cancer during
      continuous venous insult (infusion of 5-fluorouracil-based chemotherapy).
      PATIENTS AND METHODS: Between January 1999 and February 2001, we retrospectively
      analyzed the incidence of first DVT in 300 consecutive patients with locally
      advanced or metastatic breast cancer treated at a single institution with a
      combination of chemotherapy administered continuously through a totally implanted
      access port. We identified 25 women (study group) with catheter-related DVT. For
      each of the 25 patients, we selected 2 women eligible for identical chemotherapy
      who had similar age, stage of disease, and prognostic features as a control
      group. The prothrombotic FVL and prothrombin mutation G20210A genotype analyses
      were performed in all patients. Analyses were performed on blinded samples, and
      all patients signed a specific informed consent form. A total of 25 cases (with
      thrombosis) and 50 frequency-matched controls were evaluated for FVL. RESULTS:
      Five cases and 2 controls were found with the mutation in the FVL, for incidences
      of 20% (95% CI, 9%-39%) and 4% (95% CI, 1%-14%), respectively. Thus, the
      frequency of the mutation was significantly higher in the cases than in controls
      (P = 0.04), and a logistic regression analysis, adjusted by age, yielded an odds
      ratio of 6.1 (95% CI, 1.1%-34.3%; P = 0.04). Time from start of infusion
      chemotherapy to thrombosis was not significantly different between those with the
      mutation (median, 31 days) and without the mutation (median, 43 days; P = 0.6).
      Only 1 subject (in the case group) was found with the G20210A mutation in the
      prothrombin gene. CONCLUSION: Factor V Leiden carriers with locally advanced or
      metastatic breast cancer are at high risk of catheter-related DVT during
      chemotherapy. Clinicians should be aware of this increased risk, and alternative
      cytotoxic treatments not requiring continuous infusions should be considered for
      these patients.

PMID- 18632447
TI  - Darbepoetin alfa as primary prophylaxis of anemia in patients with breast cancer
      treated preoperatively with docetaxel/doxorubicin/cyclophosphamide.
AB  - BACKGROUND: At present, the combination of docetaxel/doxorubicin/cyclophosphamide
      (TAC) is considered a treatment option for patients with node-positive primary
      breast cancer; however, treatment is associated with grade 1-4 anemia in up to
      95% of patients (grade 2-4 in 36%). PATIENTS AND METHODS: We prospectively
      investigated the use of a primary prophylaxis with darbepoetin alfa once every 3
      weeks in 35 patients receiving 6-8 cycles of TAC as neoadjuvant treatment for
      breast cancer. Darbepoetin alfa treatment was started on day 1 of a TAC cycle if
      hemoglobin (Hb) level was </= 14 g/dL. The dose was adapted to 9 mug/kg if Hb
      level was </= 13 g/dL on day 21 of the previous cycle, to 4.5 mug/kg if Hb level
      was between 13 g/dL and 14 g/dL, and was discontinued if Hb level increased to
      >/= 14 g/dL. The primary aim was to prevent Hb levels </= 12 g/dL before surgery.
      RESULTS: During 112 (50.2%) and 93 (41.7%) of 223 cycles, 4.5 mug/kg and 9 mug/kg
      of darbepoetin alfa were given, respectively. The dose was decreased from 9
      mug/kg to 4.5 mug/kg in 21 patients (60%) and in 28 cycles (12.4%). Treatment was
      discontinued because of Hb levels > 14 g/dL in 12 patients (34.3%) and in 13
      cycles (5.4%). Hemoglobin level on day 21 of the last cycle was </= 12 g/dL in 4
      patients (11.4%). Eighteen patients (51.4%) during 36 cycles (16.1%) showed Hb
      levels </= 12 g/dL throughout treatment. No National Cancer Institute Common
      Toxicity Criteria grade 2-4 anemia was observed. Symptoms of fatigue (Functional
      Assessment of Cancer Therapy-Anemia) decreased slightly throughout treatment.
      CONCLUSION: Anemia during TAC chemotherapy can be avoided by a single injection
      of darbepoetin alfa every 3 weeks.

PMID- 18632448
TI  - Reasons for poor accrual in palliative radiation therapy research studies.
AB  - BACKGROUND: Patients with advanced-stage cancer commonly have multiple symptoms,
      poor performance status, and limited life expectancies. Despite the need for
      evidence-based practice and guidelines for palliative radiation therapy (RT),
      conducting clinical palliative research has proven to be a challenge in the past
      because of low accrual rates and high patient attrition. We explore the change in
      accrual rates, reasons for nonparticipation in palliative RT clinical research
      trials, and factors that contributed to the increase in accrual over a 3-year
      period. PATIENTS AND METHODS: A record was kept for all patients seen at the
      Rapid Response Radiotherapy Program between 2002 and 2005, including information
      on patient demographics, disease characteristics, and whether patients were
      accrued into >/=1 palliative research study at the time of clinic visit. If a
      patient did not participate in a study, the reason for nonaccrual was recorded.
      RESULTS: Despite previous difficulties, changes to the methods of conducting
      palliative research and study design have resulted in an increase in patient
      accrual, from 14% to an average of approximately 60%. The implementation of a
      full-time clinical research assistant and a simple study design with realistic
      eligibility criteria contributed to the increase in patient participation.
      CONCLUSION: Difficulties in conducting palliative clinical research trials were
      improved through changes in study design and research administration. Future
      clinics should use a dedicated clinical research assistant responsible for
      patient recruitment and study management. Studies should be designed specifically
      for the patient population receiving palliative care and should involve clearly
      defined and realistic eligibility criteria and brief assessments.

PMID- 18632449
TI  - Increasing the number of patients in palliative research: ethical considerations.

PMID- 18632450
TI  - Osteonecrosis of the jaw, a recently recognized sequela of bisphosphonate
      therapy: case report.
AB  - In the oncologic setting, osteonecrosis, which generally occurs after a temporary
      or permanent loss of blood supply to the bones, is frequently caused by radiation
      or combined chemoradiation therapy, particularly in head and neck cancers.
      However, this well-recognized phenomenon remains relatively rare. Recently, cases
      of osteonecrosis of the jaw have been reported over a 2-year period, with the
      majority occuring in oncology patients, the only commonality being the use of
      bisphosphonate therapy. Herein, we report a patient with breast carcinoma
      metastatic to bone that developed osteonecrosis that ultimately resolved with
      supportive measures. She was successfully rechallenged with bisphosphates without
      recurrence or sequelae.

PMID- 18632451
TI  - Erythropoietic therapy: who, how, and when?

PMID- 18632453
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18632452
TI  - Words that make a difference: enhancing the "how" in "how we say it".

PMID- 18632454
TI  - Cell coupling in mouse pancreatic beta-cells measured in intact islets of
      Langerhans.
AB  - The perforated whole-cell configuration of the patch-clamp technique was applied
      to functionally identified beta-cells in intact mouse pancreatic islets to study
      the extent of cell coupling between adjacent beta-cells. Using a combination of
      current- and voltage-clamp recordings, the total gap junctional conductance
      between beta-cells in an islet was estimated to be 1.22 nS. The analysis of the
      current waveforms in a voltage-clamped cell (due to the firing of an action
      potential in a neighbouring cell) suggested that the gap junctional conductance
      between a pair of beta-cells was 0.17 nS. Subthreshold voltage-clamp
      depolarization (to -55 mV) gave rise to a slow capacitive current indicative of
      coupling between beta-cells, but not in non-beta-cells, with a time constant of
      13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a
      superficial beta-cell in an islet is in electrical contact with six to seven
      other beta-cells. No evidence for dye coupling was obtained when cells were
      dialysed with Lucifer yellow even when electrical coupling was apparent. The
      correction of the measured resting conductance for the contribution of the gap
      junctional conductance indicated that the whole-cell KATP channel conductance
      (GK,ATP) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at
      15 mM glucose with an estimated IC50 of approximately 4mM. Theoretical
      considerations indicate that the coupling between beta-cells within the islet is
      sufficient to allow propagation of [Ca2+]i waves to spread with a speed of
      approximately 80 microms-1, similar to that observed experimentally in confocal
      [Ca2+]i imaging.

PMID- 18632455
TI  - A new strategy for assessing sensitivities in biochemical models.
AB  - An integral part of any systems biology approach is the modelling and simulation
      of the respective system under investigation. However, the values of many
      parameters of the system have often not been determined or are not identifiable
      due to technical experimental difficulties or other constraints. Sensitivity
      analysis is often employed to quantify the importance of each of the model's
      parameters in the behaviour of the system. This approach can also be useful in
      identifying those parts of the system that are most sensitive with the potential
      of becoming drug targets. A problem of the commonly used methods of sensitivity
      analysis is that they constitute local methods meaning that they depend directly
      on the exact parameter space, which in turn is not known exactly. One way to
      circumvent this problem is to carry out sensitivity analysis over a wide range of
      values for all parameters, but this is handicapped by expensive computations when
      the systems are high dimensional. Another approach is to employ global
      sensitivity analysis, which in this context is mostly based on random sampling
      methods. In this paper we present an efficient approach that involves using
      numerical optimizing methods that search a wide region of parameter space for a
      given model to determine the maximum and minimum values of its metabolic control
      coefficients. A relevant example for drug development is presented to demonstrate
      the strategy using the software COPASI.

PMID- 18632456
TI  - Preface.

PMID- 18632457
TI  - Tremor entrainment by patterned low-frequency stimulation.
AB  - High-frequency test stimulation for tremor suppression is a standard procedure
      for functional target localization during deep brain stimulation. This method
      does not work in cases where tremor vanishes intraoperatively, for example, due
      to general anaesthesia or due to an insertional effect. To overcome this
      difficulty, we developed a stimulation technique that effectively evokes tremor
      in a well-defined and quantifiable manner. For this, we used patterned low
      frequency stimulation (PLFS), i.e. brief high-frequency pulse trains administered
      at pulse rates similar to neurons' preferred burst frequency. Unlike periodic
      single-pulse stimulation, PLFS enables one to convey effective and considerably
      greater integral charge densities without violation of safety requirements. In a
      computational investigation of an oscillatory neuronal network temporarily
      rendered inactive, we found that PLFS evokes synchronized activity, phase locked
      to the stimulus. While a stronger increase in the amount of synchrony in the
      neuronal population requires higher stimulus intensities, the portion of
      synchronously active neurons nevertheless becomes strongly phase locked to PLFS
      already at weak stimulus intensities. The phase entrainment effect of PLFS turned
      out to be robust against variations in the stimulation frequency, whereas
      enhancement of synchrony required precisely tuned stimulation frequencies. We
      applied PLFS to a patient with spinocerebellar ataxia type 2 (SCA2) with
      pronounced tremor that disappeared intraoperatively under general anaesthesia. In
      accordance with our computational results, PLFS evoked tremor, phase locked to
      the stimulus. In particular, weak PLFS caused low-amplitude, but strongly phase
      locked tremor. PLFS test stimulations provided the only functional information
      about target localization. Optimal target point selection was confirmed by
      excellent post-operative tremor suppression.

PMID- 18632458
TI  - Monitoring of chloride and activity of glycine receptor channels using
      genetically encoded fluorescent sensors.
AB  - Genetically encoded probes have become powerful tools for non-invasive monitoring
      of ions, distributions of proteins and the migration and formation of cellular
      components. We describe the functional expression of two molecular probes for non
      invasive fluorescent monitoring of intracellular Cl ([Cl]i) and the functioning
      of glycine receptor (GlyR) channels. The first probe is a recently developed cyan
      fluorescent protein-yellow fluorescent protein-based construct, termed Cl-Sensor,
      with relatively high sensitivity to Cl (Kapp approximately 30 mM). In this study,
      we describe its expression in retina cells using in vivo electroporation and
      analyse changes in [Cl]i at depolarization and during the first three weeks of
      post-natal development. An application of 40 mM K+ causes an elevation in [Cl]i
      of approximately 40 mM. In photoreceptors from retina slices of a 6-day-old rat
      (P6 rat), the mean [Cl]i is approximately 50 mM, and for P16 and P21 rats it is
      approximately 30-35 mM. The second construct, termed BioSensor-GlyR, is a GlyR
      channel with Cl-Sensor incorporated into the cytoplasmic domain. This is the
      first molecular probe for spectroscopic monitoring of the functioning of receptor
      operated channels. These types of probes offer a means of screening
      pharmacological agents and monitoring Cl under different physiological and
      pathological conditions and permit spectroscopic monitoring of the activity of
      GlyRs expressed in heterologous systems and neurons.

PMID- 18632459
TI  - Heterogeneity and weak coupling may explain the synchronization characteristics
      of cells in the arterial wall.
AB  - Vascular smooth muscle cells (SMCs) exhibit different types of calcium dynamics.
      Static vascular tone is associated with unsynchronized calcium waves and the
      developed force depends on the number of recruited cells. Global calcium
      transients synchronized among a large number of cells cause rhythmic development
      of force known as vasomotion. We present experimental data showing a considerable
      heterogeneity in cellular calcium dynamics in the vascular wall. In stimulated
      vessels, some SMCs remain quiescent, whereas others display waves of variable
      frequency. At the onset of vasomotion, all SMCs are enrolled into synchronized
      oscillation. Simulations of coupled SMCs show that the experimentally observed
      cellular recruitment, the presence of quiescent cells and the variation in
      oscillation frequency may arise if the cell population is phenotypically
      heterogeneous. In this case, quiescent cells can be entrained at the onset of
      vasomotion by the collective driving force from the synchronized oscillations in
      the membrane potential of the surrounding cells. Partial synchronization arises
      with an increase in the concentration of cyclic guanosine monophosphate, but in a
      heterogeneous cell population complete synchronization also requires a high
      conductance pathway that provides strong coupling between the cells.

PMID- 18632460
TI  - Disease management and patient-reported outcomes.

PMID- 18632461
TI  - Novel approaches in the management of myeloma-related skeletal complications.
AB  - Patients with multiple myeloma (MM) experience pathologic fractures, bone pain,
      hypercalcemia, neurologic symptoms, and renal insufficiency with substantial
      morbidity and mortality. Bisphosphonates have been used successfully for the
      management of MM-related bone disease. Increased incidence of osteonecrosis of
      the jaw has been observed in patients with cancer receiving bisphosphonate
      therapy. Recent advances in the pathobiology of MM-related bone disease and other
      cancer-related bone metastases have led to the identification of novel
      therapeutic targets, such as receptor activator of nuclear factor-kappaB (RANK);
      its ligand (RANKL); and a decoy receptor, osteoprotegerin, for the development of
      potential targeted agents. Initials studies have demonstrated that targeting
      RANK/ RANKL signaling with the fully human monoclonal antibody denosumab
      prevented skeletal complications in patients with MM and other cancers with bone
      metastases. Ongoing studies evaluating the clinical utility of denosumab in
      cancer- related bone destruction have been discussed. In addition, several
      potential targets, such as macrophage inflammatory protein-1alpha, chemokine
      receptors 1 and 5, interleukin-3, and Wnt signaling, are b riefly described.

PMID- 18632462
TI  - Optimizing the management of treatment-related peripheral neuropathy in patients
      with multiple myeloma.
AB  - Toxicity of the nervous system can be a biproduct of the use of novel agents such
      as bortezomib or thalidomide, as well as conventional agents such as vincristine
      and cisplatin in patients with multiple myeloma. Peripheral neuropathy (PN)
      involving sensory and motor nerves has emerged as an important adverse event
      associated with several recently approved novel myeloma therapies. Although PN is
      seen with varying frequency, the proportion of patients with myeloma with
      persistence or resolution of PN after treatment is not well defined. Indeed,
      currently there are no comprehensive clinical data pertaining to the proportion
      of patients experiencing treatment delays or discontinuing therapies secondary to
      PN. Moreover, in the absence of peer guidelines, the prevention and management of
      therapy-related PN tends to be ad hoc. In addition, currently there are no
      standard safe and effective treatment approaches available for the management of
      PN. Appropriate dose reductions and dose modifications are critical to minimizing
      long-term morbidity and maintaining efficacy or patients in relapsed or induction
      setting. This mini-review addresses some of the recent concerted efforts directed
      toward optimizing the management of therapy-related PN in patients with multiple
      myeloma.

PMID- 18632463
TI  - Prevention of acute radiation-induced rectal toxicity by amifostine: efficacy and
      evaluation of objective and subjective endpoints for radiation therapy-induced
      mucositis.
AB  - Often the rectum is a dose-limiting organ in curative radiation therapy of pelvic
      malignancies. It results in serous, mucoid, or more rarely bloody diarrhea. There
      are few reports on the cytoprotective effect of amifostine in the radioprotection
      against rectal mucositis. Among 10 studies published in Medline, significant (P <
      0.05) grade I-III acute toxicity was reported, and amifostine was used before
      irradiation in pelvic areas. Although the strength of the evidence is variable,
      it seems that there is a radioprotective effect, especially with intrarectal
      administration of amifostine. The cytoprotection seems to be effective in terms
      of symptomatic and objective (rectosigmoidoscopy) endpoints. However, there is a
      need for well designed clinical trials with sufficient numbers of participants.
      Besides, there is a need for accurate endpoints for evaluating acute rectal
      radiation toxicity. The rectosigmoidoscopy with objective measurements is
      superior to subjective parameters such as World Health Organization or Radiation
      Therapy Oncology Group/European Organization for Research and Treatment of Cancer
      toxicity grading scales. We propose a system of combining the objective
      rectosigmoidoscopy with subjective World Health Organization or Radiation Therapy
      Oncology Group/European Organization for Research and Treatment of Cancer
      toxicity scales for grading radiation therapy-induced acute rectal toxicity. This
      system could be accurate and user-friendly with good clinical reliability and
      validity.

PMID- 18632464
TI  - Management of hot flashes in men with prostate cancer being treated with androgen
      deprivation therapy.
AB  - The use of androgen deprivation therapy (ADT) to treat prostate cancer has
      favorably impacted outcomes for men with prostate cancer. Androgen deprivation
      therapy is effective in reducing painful bony metastases and soft tissue visceral
      disease in advanced-stage prostate cancer. The use of ADT has expanded beyond the
      metastatic setting and can also be used as adjuvant therapy for patients with
      locally advanced prostate cancer who received surgery or localized radiation
      therapy. Luteinizing hormone-releasing hormone agonists are the most common
      medical therapy used to deprive men of androgen production. Despite the
      beneficial effects that ADT has on prostate cancer, ADT causes side effects that
      can impair quality of life. This article will review the impact and treatment of
      hot flashes in men treated for prostate cancer.

PMID- 18632465
TI  - Hot flash therapies in breast cancer survivors.
AB  - More than 86% of those diagnosed with invasive breast cancer are expected to
      survive for >/= 5 years after their diagnosis. Approximately 75% of
      postmenopausal women who had breast cancer report experiencing hot flashes. More
      than 90% of young survivors also experience hot flashes, which can be more severe
      and long lasting, with iatrogenic ovarian ablation or antiestrogen therapy. There
      are numerous options for the treatment of hot flashes. Not one treatment fits
      all. Some treatments are generally more effective than others, and each has
      different side effects. This review is meant to provide the basic information
      needed to make a decision about the best treatment for a breast survivor
      experiencing hot flashes.

PMID- 18632466
TI  - Effect of treatment with epoetin Beta on thromboembolic events in anemic patients
      with cancer: a metaanalysis.
AB  - PURPOSE: Epoetin therapy is associated with a slight increase in thromboembolic
      event (TEE) incidence, although causality is uncertain. This metaanalysis
      compared TEE incidence in patients with cancer-related anemia treated with
      epoetin beta versus a control group (placebo or standard treatment) and
      investigated the impact of hemoglobin (Hb) parameters on thromboembolic risk.
      PATIENTS AND METHODS: Patients from 9 randomized trials were pooled (epoetin beta
      group, n = 800; control group, n = 613). Adverse event reports were reviewed for
      all TEEs recorded during treatment and 28 days thereafter. Thromboembolic event
      incidence was compared between 2 groups, and standard statistical analyses were
      conducted to investigate the potential of Hb parameters to modulate
      thromboembolic risk. RESULTS: For epoetin beta, 5.9% of patients (n = 47)
      experienced >/= 1 TEE versus 4.2% of controls (n = 26; not
      significant).Thromboembolic-related mortality rates were 1% in both groups.
      Thromboembolic event rates in patients stratified by tumor type were consistent
      with the overall population. For epoetin beta, greater baseline-adjusted Hb area
      under the concentration-time curve and greater Hb increases during the first 4
      weeks of treatment significantly correlated with reduced risk of TEEs.
      Conversely, treatment in those with higher baseline Hb levels was associated with
      increased TEE risk. CONCLUSION: When administered in accordance with European
      Organization for Research and Treatment of Cancer guidelines, epoetin beta did
      not appear to be associated with increased thromboembolic risk. Although risk of
      TEEs might be marginally increased in patients with cancer treated with epoetin
      beta, there is no increased risk of thromboembolic mortality.

PMID- 18632467
TI  - An open-label pilot study to evaluate a flexible dosing regimen of epoetin alfa
      for the treatment of chemotherapy-induced anemia: 60,000 units weekly followed by
      60,000 units every 2 weeks.
AB  - PURPOSE: This open-label, single-arm pilot study assessed the safety and efficacy
      of administering an Initials epoetin alfa dose of 60,000 U subcutaneously once
      weekly (Initials dosing phase [IDP]) followed by an extended dose regimen of
      60,000 U subcutaneously every 2 weeks (extended dosing phase [EDP]). PATIENTS AND
      METHODS: Patients who had a hematologic response, defined as hemoglobin (Hb)
      level increase >/= 1 g/dL from week 1 baseline at any time during the 4-week IDP
      (the primary efficacy endpoint), were eligible to enter the EDP at week 5 and
      receive every-other-week treatment for up to 12 additional weeks. Patients who
      did not exhibit this increase in the IDP were withdrawn. RESULTS: Fifty-one
      patients were enrolled; the mean baseline Hb level was 10.1 g/dL +/- 0.79 g/dL.
      Thirty-three patients (64.7%) met the primary efficacy endpoint of Hb increase
      >/= 1 g/dL during the IDP; 29 patients (56.9%) proceeded to the EDP. Mean Hb
      level at entry to the EDP was 12.4 g/dL +/- 0.99 g/dL. Further Hb increase in the
      EDP (average Hb level >/= week 5 Hb value) was achieved in 12 of 29 patients
      (41.4%). Final Hb value for patients in the EDP was 11.7 g/dL +/- 1.28 g/dL. Four
      patients received a total of 5 red blood cell transfusions during the study.
      Epoetin alfa was well tolerated and had a safety profile similar to that observed
      with labeled dosing. Two patients experienced a clinically relevant thrombotic
      vascular event. CONCLUSION: RESULTS from this pilot study suggest that higher
      Initials weekly dosing of epoetin alfa followed by extended dosing is safe and
      effective for treating chemotherapy-induced anemia.

PMID- 18632469
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18632468
TI  - Utility of cancer web sites for a public hospital empoli (florence), Italy
      oncology population in tuscany, Italy.

PMID- 18632470
TI  - Cancer management in the era of targeted agents.

PMID- 18632471
TI  - Highlights from: The 48th Annual Meeting of the American Society of Hematology;
      Orlando, FL.

PMID- 18632472
TI  - Epoetin alfa treatment for patients with chemotherapy-induced anemia.
AB  - Anemia (hemoglobin [Hb] < 12 g/dL) is a frequent and debilitating complication in
      the treatment of cancer. The negative effects of anemia include impairment of
      organ systems, disruption of important aspects of patient quality of life, and
      potential interference with completion and outcomes of cancer chemotherapy.
      Guidelines issued by the National Comprehensive Cancer Network and the American
      Society of Hematology/American Society of Clinical Oncology jointly suggest that
      anemia in patients with cancer be managed by restoring Hb levels to approximately
      12 g/dL, thereby minimizing transfusion requirements and resolving clinical
      symptoms associated with anemia. Recombinant human erythropoietin (epoetin alfa)
      administered 150 U/kg 3 times weekly or 40,000 U once weekly has been shown in
      randomized, double-blind, placebo-controlled trials and large, open-label,
      nonrandomized, community-based studies to effectively and safely correct anemia
      in patients with cancer undergoing chemotherapy. Several clinical trials support
      that treatment with epoetin alfa results in quality of life benefits that
      significantly correlate with Hb increases. Areas currently being investigated
      with epoetin alfa in the chemotherapy setting include the following: extended
      dosing regimens beyond the Food and Drug Administration-approved 3-times-weekly
      and once-weekly dosing regimens, early intervention for mild anemia, effects on
      treatment outcomes and survival, and optimal administration of concurrent iron
      supplementation.

PMID- 18632473
TI  - Treatment of bone metastases and bone pain with bisphosphonates.
AB  - Many solid tumors metastasize to bone, leading to debilitating skeletal
      complications such as intractable bone pain and pathologic fractures. Patients
      who experience a skeletal-related event (SRE) are at higher risk for subsequent
      events. After an SRE such as a pathologic fracture, spinal cord compression, or
      the requirement for orthopedic surgery or palliative radiation therapy, a
      patient's quality of life and functional independence could decline
      substantially. Prevention or delay of skeletal complications provides clinical
      benefit to patients with bone metastases secondary to solid tumors. Treatment for
      the prevention of the first SRE might substantially improve patients' quality of
      life, functional independence, and pain throughout the course of their disease.
      Bisphosphonates have shown a palliative benefit in this setting. In particular,
      zoledronic acid is the only bisphosphonate that has provided benefits for
      patients with bone metastases secondary to a broad range of solid tumors. Among
      patients with metastatic breast or prostate cancer, zoledronic acid has
      demonstrated significant reductions in pain and skeletal morbidity compared with
      placebo. Zoledronic acid has also shown significant reductions in skeletal
      morbidity in patients with lung cancer or other solid tumors compared with
      placebo. Pamidronate, oral clodronate, and ibandronate compared with placebo have
      each shown significant benefits in reductions of pain and skeletal complications
      for patients with metastatic breast cancer. Further improvements in the
      management of skeletal health in patients with malignant bone disease could be
      achieved through ongoing bisphosphonate investigations to optimize dose, timing,
      and duration of treatment.

PMID- 18632474
TI  - Balancing risk and benefit for first-line treatment of metastatic colorectal
      cancer: a graphic communication tool for patients and physicians.
AB  - Advances in the treatment of metastatic colorectal cancer have improved overall
      survival (OS); however, this might come at the cost of increased toxicity. Health
      related quality of life, a significant concern closely related to toxicity and
      important when discussing palliative therapy, is infrequently assessed and
      reported in older clinical trials. As the number of tested regimens increases,
      the question arises on how to best present palliative treatment options. We
      present a simple way to compare treatment options in terms of potential risks and
      benefits. The literature was surveyed for reports of first-line systemic
      chemotherapies for metastatic colorectal cancer. The largest recent reports with
      detailed toxicity data were selected as representative for a regimen. Toxicity
      sum of a regimen was calculated as percent occurrences in the study cohort of
      severe adverse effects: diarrhea, mucositis, neurocutaneous conditions (excluding
      alopecia), vomiting, and febrile neutropenia. Limitations of toxicity reporting
      precluded inclusion of other or milder adverse events. Benefits (OS and
      progression-free survival [PFS]) were plotted graphically as benefit versus
      toxicity sum. Thirty-four regimens were found. Overall survival, PFS, and
      toxicity sum ranged from 8.9-24.7 months, 4.9-9.2 months, and 12-70 months,
      respectively. Weaknesses of our study include omission of some specific
      toxicities and of symptom control benefit, as well as heterogeneity of trial
      design and study populations. Furthermore, more recent OS data might reflect the
      availability of more lines of therapy rather than the effect of the first-line
      regimen, as comparison with PFS outcomes show. Our comparative tool helps
      physicians discuss the large number of available options with a patient in order
      to arrive at the treatment plan most appropriate to the individual and improve
      informed consent and disclosure, while highlighting limitations in available
      evidence.

PMID- 18632475
TI  - Patient expectation of the partial response and response shift in pain score.
AB  - PURPOSE: The aim of this study was to define the minimum reduction in pain level
      that patients would expect and to examine whether response shift exists in the
      treatment of bone metastases with palliative radiation therapy (RT). PATIENTS AND
      METHODS: Patients with bone metastases were asked to quantify the minimal level
      of pain reduction by 2 months that they considered would justify the palliative
      RT based on their current pain (on a scale of 0-10 and a 4-point scale of none,
      mild, moderate, or severe). At the 2-month follow-up, they were asked the
      conventional "post-test" question, ie, what is their level of pain now? In
      addition, they were asked to retrospectively reevaluate their baseline "pretest"
      level of pain, which is referred to as a "then-test," ie, how would they now rate
      their level of pain before RT? RESULTS: Two hundred seventeen patients were
      enrolled. The median minimum pain reduction they would expect from the radiation
      treatment at the time of consultation was 4. Patients expected a reduction of 50%
      70% in their baseline pain after radiation treatment. At 2 months, 114 patients
      participated in the response shift study. Only 31 patients reported no change
      between the pretest and then-test pain scores. The other 83 patients (73%)
      demonstrated a response shift but in opposing directions. CONCLUSION: Patients
      with bone metastases expected a 50%-70% reduction in pain score from baseline
      with the palliative RT. This might become the definition of partial response in
      future trials. Response shift was observed in this group of patients but in
      opposing directions and without affecting the overall outcome.

PMID- 18632476
TI  - Chocolate as a cough suppressant: rationale and justification for an upcoming
      clinical trial.
AB  - Cough is a troubling symptom for many patients with cancer. Current cough
      suppressants can cause side effects and, at the same time, might not provide
      absolute cough palliation. Suprisingly, accumulating evience suggests that dark
      chocolate can carry antitussive effects. Although mechanisms remain unknown, it
      is thought that theobromine, a methylxanthine intrinsic to dark chocolate, might
      potentially suppress cough. To date, clinical trials with dark chocolate have not
      been undertaken. This article describes an upcoming trial to determine whether
      dark chocolate might serve as an antitussive in patients with cancer.

PMID- 18632477
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18632478
TI  - May day.

PMID- 18632479
TI  - Highlights from: The 24th Annual Miami Breast Cancer Conference; Miami, FL; March
      14-17, 2007.

PMID- 18632480
TI  - Catheter-related thrombosis: a critical review.
AB  - The use of indwelling central venous catheters (CVCs) has improved the management
      of patients with cancer. However, these devices can be complicated by thrombosis
      because of their procoagulant state, therapies, immobility, and comorbidities. In
      addition, an indwelling CVC is a foreign body within the blood stream and can
      cause a mechanical injury during its insertion. Female sex, age, weight,
      primitive tumor (ovarian and lung adenocarcinoma), factor V Leiden, increased
      plasma levels of homocysteine, previous CVC risk of thrombosis, and chemotherapy
      as well as the material of the catheter, its tip location, the side of
      implantation insertion, and insertion time and attempts have shown relationships
      with higher rates of thrombosis. Actual data report a lower incidence of
      asymptomatic and symptomatic thrombosis (5%). This could be explained by
      technical improvement, different patient populations, and methodologic
      limitations in studies. Prophylaxis with heparins and coumarins are not supported
      by actual reliable evidence. The best treatment is not defined, but thrombolysis
      could be a simple, safe, and effective method that could decrease the rate of
      postphlebotic syndrome. A systematic phase III clinical trial should be performed
      to clarify these issues. Central venous catheter infection, postphlebitic
      syndrome, and pulmonary embolism are the most relevant complications of catheter
      related thrombosis.

PMID- 18632481
TI  - Tamoxifen-associated hot flashes in women.
AB  - PURPOSE: The most prominent toxicity from the antiestrogenic agent tamoxifen is
      hot flashes. The objective of this project was to better describe the incidence
      and severity of hot flashes in younger women receiving tamoxifen. PATIENTS AND
      METHODS: This article reports the vasomotor effects associated with the
      initiation of tamoxifen in 27 women aged < 50 years, most of whom were
      premenopausal and had received chemotherapy. It then compares the results from
      these women to results from women aged > 50 years, who participated in a previous
      similar study. Hot flash data in both studies were obtained by utilizing a
      validated hot flash diary. RESULTS: Fifty-nine percent of the women aged < 50
      years experienced significant hot flashes; women who were postmenopausal reported
      more severe trouble with hot flashes, compared with premenopausal women. There
      was a trend toward more severe hot flashes in women who had received
      chemotherapy. When data from both studies were combined and analyzed by
      menopausal status and whether hot flashes had occurred during menopause, both
      factors were related to more hot flash trouble. Hot flashes were more prominent
      in postmenopausal women who had significant previous history of hot flashes,
      compared with those without a significant history of hot flashes. CONCLUSION:
      Premenopausal women, and postmenopausal women without a previous significant
      history of hot flashes, appear to have less trouble with tamoxifen-associated hot
      flashes, compared with postmenopausal women with a previous history of moderate
      or worse hot flashes.

PMID- 18632482
TI  - Symptom clusters in patients with advanced-stage cancer referred for palliative
      radiation therapy in an outpatient setting.
AB  - PURPOSE: The aim of this study was to explore the presence of symptom clusters in
      patients with advanced cancer. PATIENTS AND METHODS: Patients with metastatic
      cancer referred to an outpatient palliative radiation therapy clinic were asked
      to rate their symptom distress using the Edmonton Symptom Assessment Scale
      (ESAS). Baseline demographic data were obtained. To determine interrelationships
      between symptoms, a principal component analysis with "varimax rotation" was
      performed on the 9 ESAS symptoms. RESULTS: Between January 1999 and January 2002,
      a total of 1296 patients with metastases provided complete baseline data on the
      ESAS. The most common primary cancer sites were lung, breast, and prostate.
      Fatigue was the highest scored symptom, followed by poor sense of well-being,
      pain, lack of appetite, and drowsiness. The 4 most prevalent symptoms were poor
      sense of well-being (92.7%), fatigue (92.2%), drowsiness (79.7%), and anxiety
      (78.7%). Three symptom clusters were found. Cluster 1 included lack of appetite,
      nausea, poor sense of well-being, and pain. Cluster 2 included fatigue,
      drowsiness, and shortness of breath. Cluster 3 included anxiety and depression.
      CONCLUSION: More work needs to be done on symptom cluster research, especially in
      setting a consensus in methodology.

PMID- 18632483
TI  - An Innovative Treatment Approach for Cancer-Related Anorexia/Cachexia and
      Oxidative Stress: Background and Design of an Ongoing, Phase III, Randomized
      Clinical Trial.

PMID- 18632484
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18632485
TI  - Becoming a supportive cancer therapy generalist.

PMID- 18632486
TI  - Clinical utility of novel agents in the treatment of central venous catheter
      occlusion.
AB  - Central venous catheter (CVC) occlusion occurs frequently and remains a
      significant clinical problem in patients with cancer receiving infusional or
      intravenous chemotherapy. Thrombotic occlusions frequently limit the benefits of
      potentially curable cytotoxic agents by interrupting the delivery of infusion of
      chemotherapy, intravenous medication, nutritional support, and blood products, as
      well as the frequent acquisition of venous blood samples for laboratory testing.
      Urokinase has been used as a thrombolytic agent for dysfunctional occluded CVCs,
      but the alterations in manufacturing practice prompted the Food and Drug
      Administration to suspend further production of urokinase in 1999. Although
      streptokinase had a potential as a thrombolytic agent in place of urokinase, the
      risk of life-threatening anaphylaxis associated with this agent prompted
      researchers to look for newer agents to dissolve CVC occlusions. Several novel
      thrombolytic agents are currently being evaluated as a potential treatment for
      patients with CVC occlusions and acute or chronic peripheral arterial occlusions.
      Alfimeprase, a recombinant fibrinolytic zinc metalloprotease, has shown promising
      clinical utility in blood clot lysis in patients with CVC occlusions and
      peripheral arterial occlusions. Based on the encouraging data, alfimeprase has
      received orphan drug designation from the Food and Drug Administration and the
      Committee for Orphan Medicinal Products of the European Medicines Agency for the
      evaluation of acute peripheral arterial occlusions as a potential indication.
      Other novel thrombolytic agents such as alteplase and reteplase are undergoing
      clinical evaluation for their utility in restoring the function of occluded CVCs.
      The clinical potency of these novel agents and their ongoing clinical trials are
      discussed briefly herein.

PMID- 18632487
TI  - Novel neurokinin-1 antagonists as antiemetics for the treatment of chemotherapy
      induced emesis.
AB  - Despite significant advances in supportive care in oncology, many patients with
      cancer still experience chemotherapy- induced nausea and vomiting (CINV).
      Historically, there were only 3 neurotransmitter receptors (dopamine D2,
      cannabinoid- 1, and 5-hydroxytryptamine-3) that were the known targets for
      antiemetic therapy. Major advances in the management of chemotherapy-induced
      emesis were seen with the introduction of 5-hydroxytryptamine-3 receptor
      antagonists, which include palonosetron, ondansetron, tropisetron, dolasetron,
      and granisetron. However, recently, selective inhibitors of substance P have
      shown promising activity in the management of CINV in patients with cancer.
      Substance P mediates a number of biologic effects by binding to a specific
      neuroreceptor, neurokinin-1 (NK-1). Among the NK-1 receptor antagonists,
      aprepitant has been approved for the treatment of CINV. Currently, several other
      NK-1 receptor antagonists, including casopitant, vestipitant, netupitant, and
      SCH619734, are undergoing clinical evaluation for the prevention of CINV in
      patients with a variety of malignancies. The clinical potential of these novel NK
      1 receptor antagonists and their respective ongoing clinical trials for the
      management of chemotherapy-induced emesis are discussed briefly herein.

PMID- 18632488
TI  - Role of bisphosphonates for the management of skeletal complications and bone
      pain from skeletal metastases.
AB  - Bone metastases are common in patients with advanced-stage cancer; they can lead
      to skeletal complications (ie, pathologic fractures, spinal cord compression,
      tumor-induced hypercalcemia, and severe bone pain) that often require orthopedic
      surgery or palliative radiation therapy and negatively affect quality of life.
      The primary role of bisphosphonates for the management of bone metastases in
      patients with advanced-stage cancer is the prevention of these painful skeletal
      complications. In placebo-controlled trials, a number of bisphosphonates,
      including oral clodronate, oral and intravenous (I.V.) ibandronate, I.V.
      pamidronate, and I.V. zoledronic acid, have been shown to significantly reduce
      skeletal complications in patients with bone metastases from breast cancer.
      Furthermore, zoledronic acid provided benefit compared with pamidronate in
      patients with bone metastases from breast cancer in a large, comparative trial.
      Zoledronic acid also provided long-term benefits in randomized placebo-controlled
      trials in patients with bone metastases from prostate cancer, lung cancer, and
      other solid tumors, whereas other bisphosphonates that have been investigated
      have failed to demonstrate objective long-term benefits in placebo-controlled
      trials. In addition, although systemic analgesics and radiation therapy are
      primary treatments for the management of bone pain, bisphosphonates can also play
      an important secondary role in reducing bone pain associated with skeletal
      metastases. Notably, several economic analyses of bisphosphonate therapy have
      demonstrated that these agents are cost-effective by reducing health-care costs
      associated with skeletal complications and providing clinically significant
      quality of life benefits to patients with malignant bone disease.

PMID- 18632489
TI  - Mucositis management in patients with cancer.
AB  - Mucositis is an important toxicity to be aware of in anticancer therapy. It
      contributes to a reduction in cure rates from cancer. Until recently, it has been
      poorly understood and therefore has not been well managed. It causes patient
      distress, delays in treatment administration, and reductions in dose intensity,
      and it costs the health-care system a large amount of money. Mucositis has
      traditionally been associated more with hematologic malignancies than with solid
      tumors, because the incidence of severe mucositis has been much higher with the
      high-dose chemotherapy regimens used in hematologic malignancies. However, the
      chemotherapy used in solid tumors also causes mucositis and deserves further
      study. The separation between oral and gastrointestinal mucositis is potentially
      false and is being removed, with much research now investigating the entire
      alimentary canal. There are similarities and differences between radiation
      therapy- and chemotherapy-induced mucositis, and these have implications for
      treatment and prevention scheduling and type. Risk prediction is another area
      that requires more work, but there is real hope that, in the future, we might be
      able to predict who will suffer from mucositis and in which parts of the
      alimentary canal, thus enabling us to appropriately target the newer
      antimucotoxic therapies. The Mucositis Study Goup of the Multinational
      Association for Supportive Care in Cancer has recently published management
      guidelines for oral and gastrointestinal mucositis and is in the process of
      updating them. The guidelines serve as an excellent starting place for future
      mucositis research because they not only review the available treatments but also
      discuss mechanisms and epidemiology.

PMID- 18632490
TI  - Supportive care in the management of colon cancer.
AB  - Patients with colorectal cancer present a number of supportive care challenges
      including those related to the underlying disease, such as gastrointestinal
      obstruction, nausea, anorexia, and fatigue, and those caused by the treatments,
      such as oral mucositis, neuropathy, and chemotherapy-induced diarrhea. Unique
      toxicities can accompany specific routes of administration of colon cancer drugs
      such as hand-foot syndrome with oral capecitabine and continuous infusion
      fluorouracil and biliary sclerosis with intrahepatic arterial floxuridine. The
      newer targeted therapies also present new toxicities, such as cardiovascular
      events and wound-healing complications with bevacizumab and rash and
      hypomagnesemia with cetuximab. Recent additions to the therapeutic armamentarium
      have presented new challenges, such as oxaliplatin-induced peripheral neuropathy,
      capecitabine-induced hand-foot syndrome, cetuximab-induced rash, and bevacizumab
      associated arterial thrombotic events, bowel perforation, hypertension, and wound
      healing complications. This article focuses on the prevention and management of
      several of these more common symptoms and toxicities.

PMID- 18632491
TI  - Supportive care in colon cancer.

PMID- 18632492
TI  - Greater physical and psychological symptom burden in patients with grade 3/4
      chemotherapy-induced neutropenia.
AB  - BACKGROUND: Neutropenia is a common toxicity caused by chemotherapy that can lead
      to febrile neutropenia, infection, and dose reductions or delays that can
      diminish the efficacy of treatment. The relationship between chemotherapy-induced
      neutropenia and symptom burden is less well known. Recent data show a trend
      toward a greater incidence, duration, and severity of other toxicities of
      chemotherapy in patients with grade 4 neutropenia. PATIENTS AND METHODS: This
      retrospective study examined the relationship between symptom burden and
      neutropenia in the first cycle of chemotherapy, using the Cancer Care Monitor
      (CCM) to evaluate symptom burden in 5 domains: Physical Symptoms, Side Effects,
      Distress, Despair, and Neutropenia Index. Data were collected from the medical
      records of 51 adult patients with cancer who had been treated with standard 21
      day regimens without granulocyte colony-stimulating factor support. Patients had
      been assessed before treatment and at midcycle (days 6-14) for complete blood
      cell count and symptom burden. RESULTS: The symptom burden in all 5 CCM domains
      was greater in patients with grade 3 (n = 8) or grade 4 (n = 16) neutropenia at
      midcycle than in patients with grade 0-2 neutropenia. Age, chemotherapy regimen
      or dose, and day of midcycle assessment were not significantly correlated with
      the severity of symptoms. CONCLUSION: Understanding the relationship between
      symptom burden and chemotherapy-induced neutropenia can lead to more appropriate
      use of supportive care in patients treated with chemotherapy.

PMID- 18632493
TI  - Abbreviated rasburicase dosing for the prevention and treatment of hyperuricemia
      in adults at risk for tumor lysis syndrome.
AB  - BACKGROUND: The purpose of this study is to report the experience of using
      abbreviated rasburicase dosing for adult patients at risk for developing
      hyperuricemia secondary to tumor lysis syndrome. PATIENTS AND METHODS: All
      patients who received rasburicase from January 2003 through March 2004 were
      identified, and a retrospective chart review was conducted. RESULTS: Thirteen
      patients received >/= 1 dose of rasburicase for the prevention or treatment of
      hyperuricemia. Of these patients, 8 patients received 1 dose, 3 patients received
      2 doses, and 2 patients received 3 doses of rasburicase. All 13 patients
      experienced normalization of plasma uric acid levels within 24 hours (mean uric
      acid decreased from 9.1 mg/dL to 0.68 mg/dL). Mean serum creatinine decreased
      from 2.3 mg/dL to 1.6 mg/dL. No patients required hemodialysis. CONCLUSION: Our
      experience supports that abbreviated courses of rasburicase are effective in
      managing hyperuricemia in patients at risk for tumor lysis syndrome.

PMID- 18632494
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18632495
TI  - Support for supportive cancer therapy.

PMID- 18632496
TI  - Role of prophylactic antibiotics in the prevention of infections after
      chemotherapy: a literature review.
AB  - Febrile neutropenia is a serious sequel of chemotherapy and can result in
      significant morbidity and mortality. The use of prophylactic antibiotics during
      neutropenia to reduce this complication has been widely investigated. Historical
      trials that tested a variety of approaches were generally small and reported
      mixed results. Because of the lack of compelling evidence and concerns over
      emergence of resistance, international guidance has continued to recommend
      against the routine use of antibiotic prophylaxis in this setting. The 2 recently
      published, large, randomized, double-blind, placebo-controlled trials of
      levofloxacin versus placebo have challenged the reluctance to adopt the policy of
      prophylaxis. The GIMEMA trial focused on patients receiving high-dose inpatient
      chemotherapy for hematologic and solid tumors. Levofloxacin prophylaxis
      significantly reduced febrile episodes and microbiologically documented infection
      and bacteremia. In contrast, the SIGNIFICANT trial randomized patients receiving
      cyclic, outpatient, standard-dose chemotherapy for a variety of solid tumors and
      lymphoma. Significant reductions in febrile neutropenia episodes and
      hospitalization for the treatment of infection were demonstrated with
      prophylaxis. A recent metaanalysis has conclusively demonstrated a reduction in
      mortality resulting from the use of prophylactic fluoroquinolones for the
      duration of neutropenia in patients with acute leukemia and after high-dose
      chemotherapy, and for the first cycle of standard-dose chemotherapy in patients
      with solid tumors and lymphomas. An inevitable consequence of antibiotic use is
      the development of resistance. Although there is no doubt this can occur in
      individual patients and in treatment centers using fluoroquinolone prophylaxis,
      there is little evidence that patients are harmed as a result. Nevertheless, the
      induction of bacterial resistance should be avoided in principle, and more work
      is needed to limit prescribing of antibacterial agents to situations supported by
      a secure evidence base. When a secure evidence base exists, as is the case now
      for prophylaxis after chemotherapy, further work is needed to identify subgroups
      of patients who benefit most from prophylaxis so that it can be applied
      rationally and efficiently.

PMID- 18632497
TI  - Supportive care aspects of vertebroplasty and kyphoplasty in patients with
      cancer.
AB  - As cancer survival rates continue to improve, many patients with cancer
      experience an increased incidence of osteolytic bone destruction that can lead to
      vertebral collapse. Many people with vertebral compression fractures develop pain
      and spinal deformity, mainly kyphosis. Kyphosis has been associated with a
      decrease in physical function, depression, loss of independence, decreased lung
      capacity, malnutrition because of early satiety, and death. Supportive care,
      focusing on alleviating pain and enhancing or preserving function for those with
      vertebral fractures, could be approached through nonoperative and operative
      treatments and will be reviewed in this article. Current nonoperative treatments
      of pathologic compression fractures include bed rest, bracing, physical therapy,
      bisphosphonates, and analgesics. Operative treatment currently includes minimally
      invasive cement augmentation techniques, such as vertebroplasty and kyphoplasty.
      These surgical options have shown promising short-term results for the treatment
      of painful metastatic and osteoporotic vertebral compression fractures.
      Vertebroplasty and kyphoplasty have the potential to decrease morbidity and
      mortality, which will allow patients with cancer the ability to improve parts of
      their life that were halted by pain and dysfunction.

PMID- 18632498
TI  - The Severe Chronic Neutropenia International Registry: 10-Year Follow-up Report.
AB  - BACKGROUND: The Severe Chronic Neutropenia International Registry (SCNIR) was
      organized 10 years ago to improve understanding and treatment of the group of
      rare hematologic disorders causing blood neutrophil counts to be < 500/muL for
      months or years. PATIENTS AND METHODS: Patients now enrolled include those with
      severe congenital neutropenia (n = 526), cyclic neutropenia (n = 205), idiopathic
      neutropenia (n = 349), autoimmune neutropenia (n = 68), and other (n = 15). More
      than 90% (1053 of 1163) of patients in the SCNIR have been treated with
      granulocyte colony-stimulating factor (G-CSF), median dose 3.33 mug/kg per day.
      RESULTS: Granulocyte colony-stimulating factor has reduced the occurrence of
      infection, hospitalization, and antibiotics and improved patients' quality of
      life. Most patients have noted few adverse effects with G-CSF treatment.
      Osteoporosis/osteopenia has been reported in 14% of all patients, and
      myelodysplastic syndrome and acute myelocytic leukemia have occurred in 57
      patients, including severe congenital neutropenia (11.8%; 50 of 422), Shwachman
      Diamond syndrome (8.1%; 3 of 37), and 4 others. The SCNIR is an important
      resource for studies on the genetic and molecular basis for the disorders causing
      chronic neutropenia. CONCLUSION: The findings of mutations in the gene for
      neutrophil elastase as causing cyclic and congenital neutropenia, the role of
      mutations in the gene for the G-CSF receptor in the evolution of severe
      congenital neutropenia to acute myelocytic leukemia, and the importance of
      apoptosis as the cellular mechanism for several diseases causing severe chronic
      neutropenia have come from studies on these patients.

PMID- 18632499
TI  - Efficacy of Darbepoetin Alfa in the Treatment of Chemotherapy-Induced Anemia in
      Non-Hodgkin's Lymphoma.
AB  - BACKGROUND: Patients receiving chemotherapy often experience chemotherapy-induced
      anemia, which contributes to a significant reduction in their quality of life.
      This exploratory analysis assessed the efficacy, dosing, and safety of
      darbepoetin alfa administered every 2 weeks to a subset of patients with non
      Hodgkin's lymphoma and chemotherapy-induced anemia who were enrolled in 2 large,
      multicenter, open-label, community-based studies: the Successful Outcomes in
      Anemia Research (SOAR) trial and the Study to Understand and Reduce Patients'
      Anemia Symptom Severity (SURPASS). PATIENTS AND METHODS: Eligible patients were
      receiving multicycle chemotherapy and were anemic, with hemoglobin levels </= 11
      g/dL. Patients received darbepoetin alfa 3 squareg/kg every 2 weeks (SOAR; n =
      114) or 200 squareg every 2 weeks (SURPASS; n = 165). Hemoglobin levels were
      measured every 2 weeks, and quality of life assessments were recorded at baseline
      and the end of the study using the Functional Assessment of Cancer Therapy
      Fatigue (FACT-F) scale. This analysis includes patients who received >/= 1 dose
      of darbepoetin alfa. RESULTS: By week 17, 77% of patients in SOAR (95% confidence
      interval, 68%-84%) and 82% of patients in SURPASS (95% confidence interval, 76%
      88%) exhibited the target hemoglobin range (11-13 g/dL). Both every-2-week dosing
      regimens reduced the percentage of patients who required >/= 1 red blood cell
      transfusion by 2.5-fold during each study. Increases in hemoglobin levels were
      associated with improvements in FACT-F, with similar mean changes in FACT-F
      scores in both studies: 6.2 points for SOAR and 6.1 points for SURPASS.
      CONCLUSION: Darbepoetin alfa administered every 2 weeks in patients with non
      Hodgkin's lymphoma and chemotherapy-induced anemia appeared equally effective and
      well tolerated when given as a weight-based or a fixed dose.

PMID- 18632500
TI  - Pilot evaluation of aprepitant for the treatment of hot flashes.
AB  - BACKGROUND: Hot flashes are a major cause of morbidity among postmenopausal
      women, including many survivors of breast cancer. Hormone therapy decreases hot
      flashes but is not used as much as is has been because of toxicity concerns.
      Various new centrally acting agents have also been shown to decrease hot flashes.
      Aprepitan, a neurokinin-1 receptor antagonist, is a centrally active agent that
      might have the ability to decrease hot flashes. The objective of this pilot trial
      was to assess the potential efficacy and safety of aprepitant for the treatment
      of hot flashes in this patient population. PATIENTS AND METHODS: Twenty-five
      postmenopausal women, aged >/= 45 years, who were experiencing bothersome hot
      flashes (>/= 14 times per week) for >/= 1 month, were included. During the
      baseline week, general demographic characteristics and hot flash and quality of
      life data were obtained. At the beginning of the second week, patients were given
      aprepitant 80 mg per day for 4 weeks. Information about hot flashes, quality of
      life, and toxicity was collected during these 4 weeks and compared with week 1.
      RESULTS: After treatment with aprepitant for 4 weeks (n = 21), mean hot flash
      scores (frequency times mean severity) were reduced by 17%, and mean hot flash
      frequencies were decreased by 15% (from the baseline week 1). There were no
      statistically significant differences from week 1 to week 5 for any of the
      patient-reported side effects or quality of life. CONCLUSION: The decrease of hot
      flashes seen with aprepitant in this trial is less than what would be expected
      from the 20%-25% decrease often seen with a placebo. Thus, aprepitant does not
      appear to be an effective treatment for hot flashes. This study suggests that
      neurokinin receptors do not play a major role in mediating hot flashes.

PMID- 18632501
TI  - Adverse effects of bevacizumab and their management in solid tumors.
AB  - Bevacizumab is the first successful example of targeting the vasculature for the
      treatment of solid tumors. Although generally well tolerated in combination with
      different chemotherapy regimens, bevacizumab has side effects that are unique to
      this class of agents. In this review, we discuss the side effects associated with
      bevacizumab and potential treatments to ameliorate these toxicities.

PMID- 18632502
TI  - Radiation injury to the rectum and amifostine.

PMID- 18632503
TI  - Selected clinical trials in supportive cancer therapy.

PMID- 18632504
TI  - [Isn't the heart the source of energy for blood circulation? "The heart doesn't
      know the basic laws of physics"].
AB  - For hundreds of years, universal medical practice has depicted the heart to be
      the central organ, showing the heart's function as the primary source of energy
      for blood circulation, paying particular importance to the role of the heart
      valves. At present the generally accepted paradigm: the main force component of
      blood circulation is the pressure-gradient generated by the working heart. In
      serious combined illnesses of heart valves, the function of the valve is almost
      nonexistent. Based on the value of pressure in the chambers of the heart and in
      the great arteries and veins, blood flows from a place of high pressure to lower
      pressure, and should work the other way around as well. It is a fact, however,
      that even in such cases the circulation of blood is directed from the main
      arteries towards the veins: without the function of the valves--seemingly
      opposing the basic laws of physics--it keeps its original direction. Therefore we
      can justifiably infer that it isn't the work of the heart muscle that provides
      the source of energy for blood circulation. The heart has an essential function
      in the maintenance of blood circulation: pulse generation. The principal role of
      the heart is to generate pulses and not pressure.

PMID- 18632505
TI  - [Stem cell transplantation in the treatment of gastrointestinal diseases].
AB  - The stem cells with self-renewal ability are capable to form one or more cell
      types. They will be in the target of cell and gene therapy because of their
      multipotency and easy retrieval. Application of adult mesenchymal, neuronal,
      epidermal and haematopoietic stem cell can be favourable in the treatment of
      cardiac (myocardial infarction), bone (osteoarthritis), neurological
      (Parkinson's, Alzheimer's) and hematological (hemophilia, thrombocytopenia)
      disorders. Authors summarize the knowledge in connection with their application
      in the therapy of gastrointestinal diseases. Haematopoietic stem cell
      transplantation has been successful for the treatment of refractory Crohn's
      disease, as well as in selected group of celiac patients. Mesenchymal stem cell
      transplantation has been proved beneficial in the prevention of liver fibrotic
      process. It will gain more grounds in the treatment of autoimmune liver diseases:
      autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing
      cholangitis in the future. Well-designed, multicentric, prospective studies are
      needed to confirm the results of case reports and clinical studies with small
      group of patients.

PMID- 18632506
TI  - [The role of the Medical Scientific Council's Forensic Committee in the consent
      judgments regarding private insurance companies].
AB  - During recent years the Medical Scientific Council's Forensic Committee has
      provided for the professional revision of the medico-legal experts' opinions and
      settled the inconsonance between inconsistent opinions. This paper analyses the
      relationship between the revised experts' opinions in damage suits and the
      consent judgments. AIM: The author assesses and evaluates the role and importance
      of the revised experts' opinions by the Forensic Committee in the process of
      lawsuits. RESULTS: The Court has evaluated positively about two thirds of the
      revised experts' opinions and incorporated the Committee's answers to the
      forensic questions into the judgments. Sometimes it has happened that the judge
      misunderstood the basic medical and experts' opinions terms. In certain cases the
      consultant doctor of forensic medicine, the expert of social insurance and the
      doctor of the business insurance company used different terms, which resulted in
      ambiguity of terms appearing in the judgments. CONCLUSIONS: The author recommends
      to elaborate a new methodical newsletter that defines the most important experts'
      opinions terms and background knowledge regarding damages in a way which is clear
      to all, and clarifies them according to everyday practice in order to make sure
      that experts working in different fields and dispensers of justice use a common
      language.

PMID- 18632507
TI  - [The characteristics of nurses' and caregivers' behaviour in different clinical
      settings with special attention to burnout syndrome].
AB  - The author draws attention to the up-to-datedness of the selected topic and its
      personal and institutional effects. Stress in work (workplace stress) has a
      significant role in the pathomechanism of burnout. Nurses are exposed to
      excessive stress burden in work so expected incidence of burnout is relatively
      high among them. Goal of this study is to draw a picture about the situation,
      condition of mental health, degree and rate of burnout in nurses in given health
      care situations. METHODS: Self-completed, anonymous questionnaire questioning the
      surveyed socio-demographic data while using three standardized questionnaires
      with the measurement of the degree of burnout, physical and mental exhaustion and
      fatigue as well as dysfunctional attitudes. RESULTS: The study surveyed 805
      individuals analyzing the specific characteristics of supporting relationship and
      joining points between degree of burnout and (hospital) department care form.
      Among 374 nurses working in the intensive care unit 9.4% suffer from burnout,
      while among 155 nurses working in active care unit this rate is 0.6%. According
      to the findings of the study there are also other influential elements, namely
      the facts that nurses have part-time jobs (second jobs) besides their full-time
      jobs and the lack of moral and financial respect or recognition. Among the
      surveyed population 273 individuals--33.9%--are at risk regarding burnout, 44
      individuals--5.5%--show signs of burnout and 7 individuals--0.9%--are in a
      condition where treatment is needed. The study supposed the influential role of
      certain personality factors (dysfunctional attitudes) in the development of
      burnout. Comparison showed that burnout phenomenon and dysfunctional attitudes
      are correlated. CONCLUSION: The survey results confirmed that socio-demographic
      factors had no effect on burnout development. The severity of patients' condition
      and the degree of permanent stressful situation in intensive care units are among
      determinant workplace factors.

PMID- 18632508
TI  - [Mantle cell lymphoma: case report].
AB  - Mantle cell lymphoma (MCL) is a moderately aggressive disease, which is not
      curable with chemo-immunotherapy. The median survival duration is short,
      approximately three years. Most of the patients have advanced stage disease at
      the time of diagnosis. Fifty percent of the patients show infiltration of the
      bone marrow, in 25% of the MCL patients the gastrointestinal tract is involved,
      in 25% of patients leukaemic transformation occurs. The tumor cells express pan-B
      cell markers and the T-cell marker CD5. The overexpression of cyclin D1 was found
      as another marker for mantle cell lymphoma. Combined chemotherapy, chemo
      immunotherapy, autologous peripheral stem cell (and allogenous) transplantation
      is the treatment of choice. Our two patients had prolonged survival, in spite of
      missing the best first line therapy. The survival time after the complex
      treatment (chemo-immunotherapy, irradiation, surgical intervention, autologous
      stem cell transplantation) was 80 and 90 months, respectively. In addition to the
      history of two patients, authors review the current treatment options in mantle
      cell lymphoma.

PMID- 18632514
TI  - Hitting our stride.

PMID- 18632515
TI  - Urinary N-telopeptide is a rapid predictor of response to and palliative benefit
      from bisphosphonate therapy in patients with metastatic breast cancer.
AB  - Bone is the most common site of metastases in patients with advanced breast
      cancer. In these patients, the primary aim of therapy is to prevent and delay the
      occurrence of skeletal-related events (SREs), which can be defined as follows:
      (1) pain requiring radiation or surgical intervention, (2) spinal cord
      compression, (3) pathologic fracture, or (4) hypercalcemia. Unfortunately,
      determining which patients are at highest risk for an SRE is difficult with
      current imaging techniques. In contrast, the urinary biomarker of bone
      resorption, collagen N-telopeptide, is under intensive study after repeat
      validation as a rapid and reliable predictor of SREs as well as prognosis and
      survival. Herein, we review this new role of collagen N-telopeptide as a
      predictor of bone involvement and response to treatment, and of the palliative
      benefit of bisphosphonate therapy in patients with metastatic breast cancer.

PMID- 18632516
TI  - The effect of palifermin on chemotherapyand radiation therapy-induced mucositis:
      a review of the current literature.
AB  - Oral mucositis is a painful ulceration of the mucosal lining of the oropharynx.
      It occurs frequently in patients receiving radiation therapy and/or chemotherapy
      for solid tumors and has been reported in up to 98% of patients undergoing
      hematopoietic stem cell transplantation. The development of mucositis is
      associated with significant morbidity, including longer hospital stays, increased
      bacteremia, and pain that interferes with talking, eating, and sleeping.
      Palifermin, a recombinant humanized keratinocyte growth factor, is the first
      pharmacologic agent that has been Food and Drug Administration-approved to
      decrease the incidence and duration of mucositis in patients with hematologic
      malignancies receiving chemotherapy requiring hematopoietic stem cell
      transplantation support. Results from phase I/II trials suggest that it might
      also benefit patients receiving treatment for solid tumors; however, the results
      from ongoing phase III trials will need to be available and examined before it
      can be incorporated into general clinical practice for this patient population.

PMID- 18632517
TI  - Sunshine and rash: testing the role of sunscreen to prevent epidermal growth
      factor receptor inhibitor-induced rash.
AB  - Most patients who receive epidermal growth factor receptor (EGFR) inhibitors
      develop a rash. To date, no effective palliative therapy has been developed for
      these rashes. This review describes the rationale behind N05C4, a placebo
      controlled trial of sunscreen as an intervention to prevent EGFR inhibitor
      related rash.

PMID- 18632518
TI  - Rapid and sustained influence of intravenous zoledronic Acid on course of pain
      and analgesics consumption in patients with cancer with bone metastases: a
      multicenter open-label study over 1 year.
AB  - BACKGROUND: Bone metastases might lead to severe bone pain, pathologic fractures,
      and hypercalcemia. Osteolytic destruction is caused by the activation of
      osteoclasts by release of tumor-derived stimulating factors. Bisphosphonates are
      known to inhibit osteoclast function and, therefore, to alleviate the adverse
      effects of tumor-induced bone resorption. PATIENTS AND METHODS: We investigated
      the effects of zoledronic acid on bone pain and use of analgesic medication in
      604 patients with cancer with bone metastases in an openlabel multicenter study
      over 1 year. Patients were treated with a maximum of 12 infusions (4 mg) every 3
      or 4 weeks. RESULTS: During treatment, the mean visual analog score value for
      pain (mm) decreased by 13.9 +/- 32.3 from 37.1 +/- 28.2 to 23.3 +/- 24.2 (P <
      .0001, t test, intent-to-treat population, n = 410) and the mean analgesic score
      decreased by 0.56 +/- 1.42 from 1.84 +/- 1.53 to 1.28 +/- 1.63 (P < .0001, t
      test). A statistically significant reduction in visual analog score pain could be
      observed within 1 week after initiation of treatment. Application of zoledronic
      acid was safe and well tolerated. CONCLUSION: Treatment with zoledronic acid in
      patients with cancer with bone metastases in a broad range of tumor types
      provides substantial benefit in terms of pain relief.

PMID- 18632519
TI  - Palmar-plantar erythrodysesthesia in patients receiving capecitabine and
      intratumor thymidine phosphorylase and dihydropyrimidine dehydrogenase: is there
      a pharmacologic explanation?
AB  - BACKGROUND: Palmar-plantar erythordysesthesia (PPE) is the most common toxicity
      of capecitabine. Preclinical studies have shown that radiation therapy (RT)
      upregulates thymidine phosphorylase (TP), which could in turn increase the
      efficacy of capecitabine. Capecitabine is degraded by dihydropyrimidine
      dehydrogenase (DPD), and a deficiency in this enzyme can increase the toxicity of
      capecitabine. However, the effect of radiation therapy on frequency of PPE and
      association with TP and DPD has not been fully characterized. PATIENTS AND
      METHODS: Toxicity data were collected prospectively in 33 patients and
      retrospectively in 25 patients with locally advanced pancreatic cancer enrolled
      in 3 clinical trials who received capecitabine/RT followed by capecitabine alone.
      Tumor specimens on 33 patients were procured via endoscopic ultrasonography
      standards 1 week befoer RT and 2 weeks after RT to evaluate TP and DPD messenger
      RNA levels. Roche grading was used to assess PPE. RESULTS: Among 58 patients, 14
      (24%) developed PPE. The capecitabine group tended to have a higher incidence of
      PPE than the capecitabine/RT group (17.2% vs. 10.3%; P = .12). Grade 2/3 PPE, was
      observed in 15.5% of patients receiving capecitabine and 1.7% of patients
      receiving capecitabine/RT (P = .0078; overall: 17.2%). Median cumulative dose of
      capecitabine for first development of PPE was 235,000 mg/m2 in the
      capecitabine/RT group, and 3,185,000 mg/m2 in the capecitabine group, with the
      relative frequency of an event occurring in the capecitabine/RT arm versus
      capecitabine of 0.59. Time to occurrence of first episode of PPE was a median of
      5 weeks with capecitabine/RT and 6 weeks with capecitabine. Log-rank test showed
      that neither age, sex, performance status, nor ethnicity were associated with
      development of PPE. There was no clear difference in tumor responses of patients
      who had PPE versus those who did not have PPE. Mean tumor TP level was higher
      among patients with versus without PPE (275.77 vs. 215.29; P = .32). Mean tumor
      DPD level was lower among patients with versus without PPE (55.18 vs. 63.58; P =
      .49). Mean TP-DPD ratio was higher among patients with versus without PPE (10.29
      vs. 3.04; P = .31). CONCLUSION: No significant association of PPE with higher
      tumor thymidine phosphorylase or lower tumor DPD levels was found. There was no
      difference in the incidence, severity, or time to occurrence of PPE with
      capecitabine/RT versus capecitabine, indicating no effect of RT. Further studies
      to evaluate the underlying mechanism of PPE are required.

PMID- 18632520
TI  - Phase II Evaluation of Desipramine for the Treatment of Hot Flashes.
AB  - PURPOSE: Newer antidepressants with serotonergic effects reduce hot flashes
      significantly better than placebo. This pilot study was designed to test the
      efficacy of desipramine, an older antidepressant targeting norepinephrine, in
      women desiring therapy for hot flashes and to evaluate the toxicity of
      desipramine. PATIENTS AND METHODS: In this nonrandomized trial, eligible women
      were required to have reported >/= 14 bothersome hot flashes per week for >/= 1
      month. After an Initials baseline week in which no study medication was taken,
      participants started with desipramine 25 mg daily, which was titrated to100 mg
      daily by week 5. The primary endpoint was change from baseline in hot flash
      frequency and hot flash score. Statistical methods involved paired t tests for
      continuous variables and Fisher exact tests for categoric variables. RESULTS:
      Twenty-six patients were enrolled on this study between March 2004 and November
      2005. The decrease in mean hot flash frequency over 4 weeks of treatment was 23%,
      with a 31% reduction in hot flash scores. Seven patients (30%) withdrew early
      because of toxicities consisting of insomnia, nausea, headaches, and/or feeling
      frightened. CONCLUSION: Desipramine did not reduce hot flashes beyond the 25%-30%
      reduction that would be expected with placebo, based on previous work. Therefore,
      data from this trial do not support further study of this agent for treatment of
      hot flashes. It is of physiologic interest that this older antidepressant,
      classified as a tricyclic, did not achieve a clinically significant reduction in
      hot flash scores in this pilot trial.

PMID- 18632521
TI  - An extended dosing regimen of epoetin alfa 60,000 units every 2 weeks in anemic
      patients with cancer receiving chemotherapy.
AB  - PURPOSE: This open-label study evaluated the safety and efficacy of epoetin alfa
      60,000 U once weekly Initialsly followed by 60,000 U every 2 weeks in anemic
      patients with cancer receiving chemotherapy. PATIENTS AND METHODS: Patients
      receiving weekly or every- 4-weeks chemotherapy regimens for nonmyeloid
      malignancy and with hemoglobin (Hb) level </= 11 g/dL were enrolled. They
      received epoetin alfa 60,000 U weekly during the Initials dosing phase (IDP) to a
      target Hb level of 12 g/dL. Patients who did not exhibit target Hb level within
      12 weeks were withdrawn. Patients who had a hemogloblin level of 12 g/dL during
      the IDP entered the extended dosing phase (EDP), where epoetin alfa 60,000 U was
      administered every 2 weeks. Total maximum study duration was 24 weeks. RESULTS: A
      total of 129 patients (mean baseline Hb level, 10 g/dL) were enrolled and
      received >/= 1 dose of epoetin alfa. Sixty-eight percent of patients had
      hematopoietic response (Hb increase >/= 2 g/dL from baseline or Hb level >/= 12
      g/dL during the IDP; primary endpoint). Eighty-four patients entered the EDP; 74
      of 84 patients (88%) maintained average Hb level between 11 g/dL and 13 g/dL up
      to time of withdrawal or study completion. Adverse events were consistent with
      the underlying disease process and chemotherapy treatment. Six patients (4.7%) in
      the IDP and 8 patients (9.5%) in the EDP experienced clinically relevant
      thrombotic vascular events. CONCLUSION: In this study, approximately 90% of
      patients receiving an extended dosing regimen of epoetin alfa 60,000 U every 2
      weeks were able to maintain Hb level between 11 g/dL and 13 g/dL.

PMID- 18632522
TI  - Symptom Burden for Patients with Metastatic Colorectal Cancer Treated with First
      Line FOLFOX or FOLFIRI with and Without Bevacizumab in the Community Setting.
AB  - BACKGROUND: FOLFOX (oxaliplatin/leucovorin/5-fluorouracil) and FOLFIRI
      (irinotecan/leucovorin/5-fluorouracil) with or without bevacizumab have become
      standard-of-care regimens in first-line treatment of metastatic colorectal
      cancer. However, there is a paucity of symptom burden information regarding these
      regimens from the patient perspective in community oncology. PATIENTS AND
      METHODS: This retrospective chart review and telephone interview study examined
      patients with first-line metastatic colorectal cancer from 5 community oncology
      centers treated with FOLFOX or FOLFIRI with and without bevacizumab.
      Patientreported outcomes were taken from the Patient Care Monitor 1.0 Revised, a
      validated tablet computer-based questionnaire that measures symptom burden and
      several scales of functioning and quality of life. A subset of patients completed
      structured telephone interviews about the impact of treatment on practical
      activities and income. RESULTS: Eighty-eight patients with an average age of 62
      years were included. Patients completed a median of 8 cycles of treatment. The
      most common moderate to severe symptom complaint was fatigue. Gastrointestinal
      symptoms were common but did not cluster in one regimen versus another.
      Neuropathyrelated symptoms were also common across all regimens except FOLFIRI
      without bevacizumab. Nausea and neutropenia were common indications for
      concomitant medications. One third reported work and other activity interference,
      and care produced outof- pocket expenditures in excess of $1000. CONCLUSION:
      Although sample size was small in the FOLFIRI-based regimens, patient reports and
      chart records suggested that there was not a systematic difference between FOLFOX
      and FOLFIRI regimens in type of symptom. The addition of bevacizumab did not
      appear to increase symptom burden.

PMID- 18632523
TI  - Topiramate in the treatment of neuropathic pain in patients with cancer.
AB  - INTRODUCTION: Neuropathic pain has been reported to affect 40%-50% of patients
      with cancer. PATIENTS AND METHODS: Consecutive patients selected from the
      outpatient/adult patient palliative care clinic of the Roudebush Veterans Affairs
      Medical Center and the Indiana University Palliative Clinic were reviewed. A
      verbal pain linear analogue assessment scale was used to assess neuropathic pain.
      Pain medication history was also reviewed in addition to percent pain relief. The
      following variables were extracted from the medical record: pain characteristics,
      location, cause, date of initiation of therapy, maximal tolerated dose, pain
      scores on the visit of optimal tolerated dose, other concurrent medications,
      number of months of pain before initiation of topiramate therapy, and total
      duration of topiramate therapy. Decrease in worst, best, and average pain was
      recorded, as were the development of any adverse effects. RESULTS: Of the 13
      patients on second- and third-line therapy, 53.8% had >/= 30% decrease in worst
      pain; 69.2% had >/= 30% decrease in average pain, and 53.8% had >/= 30% decrease
      in best pain. Eight of 13 patients (61.5%) experienced adverse effects. Five
      patients discontinued (38.5%) topiramate because of adverse events. CONCLUSION:
      Because our retrospective study showed topiramate to be a beneficial second- and
      third-line therapy in patients with cancer who did not experience adequate pain
      control on previous regimens, further prospective studies are needed to establish
      this medication in the armamentarium of neuropathic cancer pain management.

PMID- 18632524
TI  - A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of
      Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A
      Currently Accruing URCC CCOP Cancer Control Study.
AB  - Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as
      ondansetron and granistron, up to 70% of patients with cancer receiving highly
      emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting.
      Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after
      chemotherapy administration) and anticipatory nausea (nausea that develops before
      chemotherapy administration, in anticipation of it) are poorly controlled by
      currently available antiemetic agents. Scientific studies suggest that ginger
      (Zingiber officinale) might have beneficial effects on nausea and vomiting
      associated with motion sickness, surgery, and pregnancy. In 2 small studies of
      patients with cancer receiving chemotherapy, addition of ginger to standard
      antiemetic medication further reduced the severity of postchemotherapy nausea.
      This article describes a phase II/III randomized, dose-finding, placebo
      controlled, double-blind clinical trial to assess the efficacy of ginger for
      nausea associated with chemotherapy for cancer. The study is currently being
      conducted by private practice oncology groups that are funded by the National
      Cancer Institute's Community Clinical Oncology Program and affiliated with the
      University of Rochester Cancer Center Community Clinical Oncology Program
      Research Base.

PMID- 18632525
TI  - Vitamin e for the prevention of chemotherapy-induced peripheral neuropathy:
      rationale for an ongoing clinical trial.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a troubling side effect that
      can lead to dose reductions and discontinuation of treatment. This can be quite
      distressing for patients. Current treatments for CIPN are limited, can have side
      effects, and are generally of limited efficacy. There is recent evidence from
      several small pilot studies that the use of vitamin E might help prevent or
      lessen the side effects of CIPN. To date, a large, randomized clinical trial
      evaluating the efficacy of vitamin E as prevention for CIPN has not been
      conducted. A clinical trial is currently being conducted by the North Central
      Cancer Treatment Group to study the relationship between vitamin E and CIPN.

PMID- 18632526
TI  - Intraductal papillary mucinous neoplasm of the pancreas: assessment of the
      likelihood of invasiveness with multisection CT.
AB  - PURPOSE: To evaluate the capabilities of multisection computed tomography (CT) in
      determining the likelihood of invasiveness of intraductal papillary mucinous
      neoplasm (IPMN). MATERIALS AND METHODS: The institutional review board approved
      this research and waived informed consent from the patients. Two radiologists
      blinded to the pathologic assessment of malignancy or parenchymal invasion of
      IPMN retrospectively evaluated CT images of 61 consecutive surgically resected
      tumors (26 adenomas, 15 noninvasive carcinomas, and 20 invasive carcinomas) in
      patients who underwent multiphase contrast material-enhanced CT with 0.5- or 1-mm
      collimation. The findings were statistically analyzed by using univariate and
      multivariate analyses, with the optimal cutoff levels of each continuous
      parameter determined by generating receiver operating characteristic curves.
      RESULTS: The following findings showed significant differences among the three
      groups: maximum diameter of the main pancreatic duct (MPD), size (length of major
      axis) of the largest mural nodule in the MPD or in any associated cystic lesion,
      abnormal attenuating area in the surrounding parenchyma, calcification in the
      lesion, protrusion of the MPD into the ampulla of Vater, and bile duct
      dilatation. An MPD diameter of 6 mm or larger, a mural nodule of 3 mm or larger,
      and an abnormal attenuating area were independently predictive of malignancy. A
      mural nodule of 6.3 mm or larger in the MPD and an abnormal attenuating area were
      independently predictive of parenchymal invasion. According to these criteria,
      the sensitivity, specificity, and accuracy for identifying malignancy were 83%,
      81%, and 82% and for identifying parenchymal invasion were 90%, 88%, and 89%,
      respectively. CONCLUSION: Multisection CT is useful for distinguishing among
      adenoma, noninvasive carcinoma, and invasive carcinoma in patients with IPMN.

PMID- 18632528
TI  - Real-time assessment of right and left ventricular volumes and function in
      patients with congenital heart disease by using high spatiotemporal resolution
      radial k-t SENSE.
AB  - PURPOSE: The purpose of this study was to compare ventricular volumes in patients
      with congenital heart disease measured by using (a) a cardiac gated sequence, (b)
      a standard real-time sequence, and (c) a radial real-time k-space and time (k-t)
      sensitivity encoding (SENSE) sequence. MATERIALS AND METHODS: The local research
      ethics committee approved this study, and written consent was obtained from all
      participants. Of 40 patients with congenital heart disease, ventricular volumes
      were measured by using the three sequences. Global image quality and motion
      fidelity were scored and compared with a Wilcoxon signed rank test. Image
      contrast, edge sharpness, and summed perimeters (the total length of the
      endocardial tracings for a given ventricle at systole and diastole) were
      quantified and compared by using paired t tests. Ventricular volumes were
      compared with paired t tests, Bland-Altman analysis, and correlation
      coefficients. RESULTS: Global image quality, motion fidelity, image contrast,
      edge sharpness, and summed perimeters were all greater for radial real-time k-t
      SENSE imaging compared with standard real-time imaging (P < .05). However, the
      gated acquisitions were significantly superior to radial real-time k-t SENSE (P <
      .05). For cardiac gated versus radial k-t real-time acquisitions, there was no
      difference between right ventricular (RV) volumes and ejection fraction (EF) (P >
      .15). There was a small difference in left ventricular (LV) end-diastolic volume
      (EDV) and thus, LV stroke volume and EF (P < .05). For cardiac gated versus
      standard real-time acquisitions, both RV and LV EDV and thus, stroke volume and
      EF were significantly lower (P < .05). CONCLUSION: Ventricular volumes and
      function can be accurately quantified by using radial k-t SENSE real-time
      imaging.

PMID- 18632527
TI  - Renal cyst pseudoenhancement at multidetector CT: what are the effects of number
      of detectors and peak tube voltage?
AB  - PURPOSE: To determine the effect of the number of detectors and peak tube voltage
      on renal cyst pseudoenhancement in a phantom model. MATERIALS AND METHODS: This
      study on computed tomographic (CT) phantoms did not require institutional review
      board approval. The renal compartments of a CT phantom were filled with iodinated
      contrast material diluted to attain attenuations of 40, 140, and 240 HU. Saline
      filled cylinders simulating cysts of varying diameters (range, 0.7-3.0 cm) were
      serially suspended in the renal compartments and scanned at 80, 90, 100, 120, and
      140 kVp in 16-detector (n = 3) and 64-detector (n = 2) CT scanners. Generalized
      estimating equations were used to determine predictors of cyst pseudoenhancement
      (defined as a >10 HU increase in cyst attenuation when the background renal
      attenuation increased from 40 to 140 or 240 HU). RESULTS: Pseudoenhancement was
      seen with higher frequency (59 [61%] of 96 cysts vs 52 [39%] of 132 cysts, P <
      .05) and magnitude (17 vs 13 HU, P < .005) with 64- rather than with 16-detector
      scanners. Pseudoenhancement was also seen with higher frequency (25 [42%] of 60
      cysts vs 11 [18%] of 60 cysts, P < .005) and magnitude (18 vs 13 HU, P < .05) at
      140 kVp than at 80 or 90 kVp. Cyst pseudoenhancement increased with higher
      background renal enhancement (P < .005) and smaller cyst diameter (P < .05). The
      number of detectors, peak tube voltage, renal parenchymal enhancement level, and
      cyst diameter were independent predictors of cyst pseudoenhancement. CONCLUSION:
      Lower tube voltage settings may be useful when accurate differentiation between
      small renal cysts and solid masses is critical, particularly for 64-detector CT
      scanners.

PMID- 18632529
TI  - Eye lens exposure to radiation in interventional suites: caution is warranted.
AB  - PURPOSE: To report estimated radiation doses to the eye lens of the
      interventionalist from procedures performed with and without use of radiation
      protection measures. MATERIALS AND METHODS: Scattered radiation doses for seven
      interventional radiology fluoroscopic systems were measured by using phantoms
      simulating patients 16-28 cm in thickness undergoing low-, medium-, and high-mode
      fluoroscopy, cine cardiac imaging, and digital subtraction angiography (DSA). The
      radiation doses to the eye lens in low- and high-dose scenarios were estimated.
      Beam angulation, biplanar equipment, working distance, procedure complexity,
      imaging collimation, and use of eyeglasses and/or protective suspended screens
      were taken into account. The doses to the lens in several procedures were
      assessed. RESULTS: Mean scattered radiation doses to the lens during fluoroscopy
      were 6.0 and 34.5 microSv/min in the low- and high-dose scenarios, respectively.
      For DSA, typical doses to the lens ranged from 0.77 to 3.33 microSv per image.
      Operation modes involving increasing or decreasing radiation doses were
      quantified. For hepatic chemoembolization, iliac angioplasty, pelvic
      embolization, and transjugular intrahepatic portosystemic shunt creation, lens
      doses ranged from 0.25 to 3.72 mSv per procedure when protection was not used.
      Lens doses in the neuroembolization procedures could exceed 10 mSv per procedure.
      CONCLUSION: With typical reported workloads, radiation doses to eye lenses may
      exceed the threshold for deterministic effects (ie, lens opacities or cataracts)
      after several years of work if radiation protection tools are not used.

PMID- 18632531
TI  - Modulation transfer function-based assessment of temporal resolution: validation
      for single- and dual-source CT.
AB  - The purpose of this study was to determine a manufacturer-independent quality
      assurance measurement for temporal resolution with a three-dimensional cardiac
      motion robot; validation was with single-source (SS) and dual-source (DS)
      computed tomography (CT). Image acquisition was performed by using standard
      cardiac protocols. Image contrast-based modulation transfer function (MTF) was
      assessed as function of time. For motion frequency of 60 beats per minute, MTF
      slightly decreased by 14% and 6% for SS CT and DS CT, respectively. For higher
      frequencies, a stronger decrease of MTF (eg, by 50% [SS CT] and 18% [DS CT] at
      120 beats per minute) was detected. Effect of manufacturer's adaptive bisegment
      algorithm for SS CT and corresponding resonance effects of rotation time and
      heart rate were quantified. The robot-based approach is a reproducible, objective
      way to assess temporal resolution; it allows practical measurement of temporal
      resolution and comparison of CT scanners and protocols.

PMID- 18632530
TI  - Cortical bone water: in vivo quantification with ultrashort echo-time MR imaging.
AB  - PURPOSE: To develop and evaluate a method based on ultrashort echo-time radial
      magnetic resonance (MR) imaging to quantify bone water (BW) concentration as a
      new metric of bone quality in human cortical bone in vivo. MATERIALS AND METHODS:
      Human subject studies were institutional review board approved and HIPAA
      compliant; informed consent was obtained. Cortical BW concentration was
      determined with custom-designed MR imaging sequences at 3.0 T and was validated
      in sheep and human cortical bone by using exchange of native water with deuterium
      oxide (D(2)O). The submillisecond T2* of BW requires correction for relaxation
      losses during the radiofrequency pulse. BW was measured at the tibial midshaft in
      healthy pre- and postmenopausal women (mean age, 34.6 and 69.4 years,
      respectively; n = 5 in each group) and in patients receiving maintenance
      hemodialysis (mean age, 51.8 years; n = 6) and was compared with bone mineral
      density (BMD) at the same site at peripheral quantitative computed tomography, as
      well as with BMD of the lumbar spine and hip at dual x-ray absorptiometry. Data
      were analyzed by using the Pearson correlation coefficient and two-sided t tests
      as appropriate. RESULTS: Excellent agreement was obtained ex vivo between the
      water displaced by using D(2)O exchange and water measured with respect to a
      reference sample (r(2) = 0.99, P < .001). In vivo, BW in the postmenopausal group
      was greater by 65% (28.7% +/- 1.3 [standard deviation] vs 17.4% +/- 2.2, P <
      .001) than in the premenopausal group, and patients with renal osteodystrophy had
      higher BW (41.4% +/- 9.6) than the premenopausal group by 135% (P < .001) and the
      postmenopausal group by 43% (P = .02). BMD showed an opposite behavior, with much
      smaller group differences. Because the majority of BW is in the pore system of
      cortical bone, this parameter provides a surrogate measure for cortical porosity.
      CONCLUSION: A new MR imaging-based method for quantifying BW noninvasively has
      been demonstrated.

PMID- 18632532
TI  - Hepatic malignancies: percutaneous radiofrequency ablation during percutaneous
      portal or hepatic vein occlusion.
AB  - PURPOSE: To prospectively evaluate the technical feasibility, effectiveness, and
      complications of percutaneous radiofrequency (RF) ablation for hepatic
      malignancies during temporary percutaneous balloon occlusion (PBO) of a large
      hepatic or portal vein. MATERIALS AND METHODS: During a 4-year period, RF
      ablation was performed in 201 patients (106 men, 95 women; age range, 41-88
      years) with 233 liver tumors. Institutional review board approval was obtained to
      attempt RF ablation during PBO for 18 tumors that were larger than 35 mm (mean,
      43 mm +/- 7.6 [standard deviation]; range, 36-60 mm) and did not abut a portal or
      hepatic vein 4 mm in diameter or larger (group 1), 58 tumors 35 mm or smaller
      (mean, 23 mm +/- 7.3; range, 12-35 mm) that abutted a large vessel (group 2), and
      20 tumors that were both larger than 35 mm (mean, 42 mm +/- 5.7; range, 38-50 mm)
      and abutted a large vessel (group 3). RF ablation without PBO was performed for
      137 tumors 35 mm or smaller (mean, 22 mm +/- 6.8; range, 9-35 mm) and remote from
      large vessels (group 4). Rate of local tumor progression was estimated with the
      Kaplan-Meier method, and tumor progression-free rates were compared between the
      four groups with the log-rank test. Complications were compared by using the
      Fisher exact test between the four groups and between the two RF devices used.
      RESULTS: PBO was achieved in 94 of 96 attempts (98%), including 64 of 64 hepatic
      veins and 30 of 32 portal branches. After a mean follow-up of 18 months +/- 9, 10
      tumors in eight patients were lost to follow-up. Local tumor progression was
      observed in six (40%) of 15 tumors in group 1, in six (11%) of 56 tumors in group
      2, in eight (40%) of 20 tumors in group 3, and in 12 (9%) of 130 tumors in group
      4. Combined analysis of tumor size and the use of PBO showed that size was the
      only prognostic factor for tumor progression, with a hazard ratio of 4.9 (95%
      confidence interval: 2.4, 9.9) (P < .001). There were no differences between
      groups 2 and 4. Asymptomatic, transient postprocedure venous thrombosis was seen
      in nine of 94 RF ablations with PBO, while occlusion of one permanent portal
      branch induced segmental liver atrophy. There were no differences in rates of
      complications (5% and 6% for RF ablation with and that without PBO,
      respectively). CONCLUSION: RF ablation with PBO provides tumor control for tumors
      smaller than 35 mm in diameter that abut vessels 4 mm or larger, equivalent to
      tumor control of the same-size tumors away from vessels. PBO does not seem to
      affect the results of RF ablation for tumors 35 mm or larger.

PMID- 18632534
TI  - The cover. Composicion universal.

PMID- 18632533
TI  - Risk of nephrogenic systemic fibrosis: evaluation of gadolinium chelate contrast
      agents at four American universities.
AB  - PURPOSE: To retrospectively determine the benchmark incidence of nephrogenic
      systemic fibrosis (NSF) related to the confirmed use of different gadolinium
      chelate contrast agents at four U.S. university tertiary care centers. MATERIALS
      AND METHODS: Institutional review board approval was obtained for this HIPAA
      compliant multi-institutional study; the requirement for informed patient consent
      was waived. Patients who had a diagnosis of NSF between January 2000 and December
      2006 were identified at four tertiary care centers with renal transplant and
      dialysis services. A standard checklist was used to acquire reliable data from
      the four centers. The diagnosis of NSF was confirmed histopathologically in all
      patients. The association of NSF development with gadolinium chelate contrast
      agent administration in each patient was assessed. The type and cumulative dose
      of contrast agent administered to each patient with NSF were determined at each
      center by using the standard checklist. The benchmark incidence of NSF was
      determined and expressed as the ratio of the number of patients with NSF who had
      undergone gadolinium chelate-enhanced magnetic resonance (MR) imaging, relative
      to the total number of patients who underwent gadolinium chelate-enhanced MR
      imaging at each tertiary care center. Benchmark incidences of NSF were compared
      among the four centers by using Fisher exact tests. RESULTS: Gadodiamide was used
      at University of North Carolina at Chapel Hill (center A) and Emory University
      (center B), and gadopentetate dimeglumine was used at Wake Forest University
      (center C) and Thomas Jefferson University (center D) during the study period.
      Twenty-three patients at center A, nine patients at center B, three patients at
      center C, and one patient at center D had NSF and had undergone gadolinium
      chelate-enhanced MR imaging. The incidence of NSF was one in 2913 patients who
      underwent gadodiamide-enhanced MR examinations and one in 44,224 patients who
      underwent gadopentetate dimeglumine-enhanced MR examinations. CONCLUSION: The
      benchmark incidence of NSF was much greater at the two centers where gadodiamide
      was used than at the two centers where gadopentetate dimeglumine was used.

PMID- 18632535
TI  - 6 EZ steps to improving your performance: (or how to make P4P pay 4U!).

PMID- 18632536
TI  - New studies target lung cancer prevention, imaging, and treatment.

PMID- 18632537
TI  - Empirically supported treatments improve care of adolescents with depression.

PMID- 18632538
TI  - Rimonabant and progression of atherosclerosis in obese persons.

PMID- 18632539
TI  - Anandamide as a marker of human disease.

PMID- 18632540
TI  - Polymorphonuclear leukocyte count in spontaneous bacterial peritonitis.

PMID- 18632541
TI  - Diagnosis of urinary incontinence.

PMID- 18632542
TI  - Physicians' duty to participate in pandemic care.

PMID- 18632543
TI  - Effect of simvastatin on cognitive functioning in children with neurofibromatosis
      type 1: a randomized controlled trial.
AB  - CONTEXT: Neurofibromatosis type 1 (NF1) is among the most common genetic
      disorders that cause learning disabilities. Recently, it was shown that statin
      mediated inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase restores
      the cognitive deficits in an NF1 mouse model. OBJECTIVE: To determine the effect
      of simvastatin on neuropsychological, neurophysiological, and neuroradiological
      outcome measures in children with NF1. DESIGN, SETTING, AND PARTICIPANTS: Sixty
      two of 114 eligible children (54%) with NF1 participated in a randomized, double
      blind, placebo-controlled trial conducted between January 20, 2006, and February
      8, 2007, at an NF1 referral center at a Dutch university hospital. INTERVENTION:
      Simvastatin or placebo treatment once daily for 12 weeks. MAIN OUTCOME MEASURES:
      Primary outcomes were scores on a Rey complex figure test (delayed recall),
      cancellation test (speed), prism adaptation, and the mean brain apparent
      diffusion coefficient based on magnetic resonance imaging. Secondary outcome
      measures were scores on the cancellation test (standard deviation), Stroop color
      word test, block design, object assembly, Rey complex figure test (copy), Beery
      developmental test of visual-motor integration, and judgment of line orientation.
      Scores were corrected for baseline performance, age, and sex. RESULTS: No
      significant differences were observed between the simvastatin and placebo groups
      on any primary outcome measure: Rey complex figure test (beta = 0.10; 95%
      confidence interval [CI], -0.36 to 0.56); cancellation test (beta = -0.19; 95%
      CI, -0.67 to 0.29); prism adaptation (odds ratio = 2.0; 95% CI, 0.55 to 7.37);
      and mean brain apparent diffusion coefficient (beta = 0.06; 95% CI, -0.07 to
      0.20). In the secondary outcome measures, we found a significant improvement in
      the simvastatin group in object assembly scores (beta = 0.54; 95% CI, 0.08 to
      1.01), which was specifically observed in children with poor baseline performance
      (beta = 0.80; 95% CI, 0.29 to 1.30). Other secondary outcome measures revealed no
      significant effect of simvastatin treatment. CONCLUSION: In this 12-week trial,
      simvastatin did not improve cognitive function in children with NF1. Trial
      Registration isrctn.org Identifier: ISRCTN14965707.

PMID- 18632544
TI  - Moderate-to-vigorous physical activity from ages 9 to 15 years.
AB  - CONTEXT: Decreased physical activity plays a critical role in the increase in
      childhood obesity. Although at least 60 minutes per day of moderate-to-vigorous
      physical activity (MVPA) is recommended, few longitudinal studies have determined
      the recent patterns of physical activity of youth. OBJECTIVE: To determine the
      patterns and determinants of MVPA of youth followed from ages 9 to 15 years.
      DESIGN, SETTING, AND PARTICIPANTS: Longitudinal descriptive analyses of the 1032
      participants in the 1991-2007 National Institute of Child Health and Human
      Development Study of Early Child Care and Youth Development birth cohort from 10
      study sites who had accelerometer-determined minutes of MVPA at ages 9 (year
      2000), 11 (2002), 12 (2003), and 15 (2006) years. Participants included boys (517
      [50.1%]) and girls (515 [49.9%]); 76.6% white (n = 791); and 24.5% (n = 231)
      lived in low-income families. MAIN OUTCOME MEASURE: Mean MVPA minutes per day,
      determined by 4 to 7 days of monitored activity. RESULTS: At age 9 years,
      children engaged in MVPA approximately 3 hours per day on both weekends and
      weekdays. Weekday MVPA decreased by 37 minutes per year [corrected], while
      weekend MVPA decreased by 39 minutes per year [corrected]. By age 15 years,
      adolescents were only engaging in MVPA for 50 minutes per weekday [corrected] and
      36 minutes per weekend day [corrected]. Boys were more active than girls,
      spending 18 and 14 more minutes per day [corrected] in MVPA on the weekdays and
      weekends, respectively. The rate of decrease in MVPA was the same for boys and
      girls. The estimated age at which girls crossed below the recommended 60 minutes
      of MVPA per day was approximately 13.2 years for weekday [corrected] activity
      compared with boys at 14.9 years [corrected], and for weekend activity, girls
      crossed below the recommended 60 minutes of MVPA at 12.7 years [corrected]
      compared with boys at 13.6 years [corrected]. CONCLUSION: In this study cohort,
      measured physical activity decreased significantly between ages 9 and 15 years.

PMID- 18632545
TI  - Update: A 35-year-old physician with opioid dependence.

PMID- 18632546
TI  - European practices of genetic information and insurance: lessons for the Genetic
      Information Nondiscrimination Act.

PMID- 18632547
TI  - The Blalock-Taussig-Thomas collaboration: a model for medical progress.

PMID- 18632548
TI  - JAMA classics: celebrating 125 years of publication.

PMID- 18632549
TI  - JAMA patient page. Neurofibromatosis.

PMID- 18632551
TI  - Ethanol's molecular targets.
AB  - Ethanol produces a wide variety of behavioral and physiological effects in the
      body, but exactly how it acts to produce these effects is still poorly
      understood. Although ethanol was long believed to act nonspecifically through the
      disordering of lipids in cell membranes, proteins are at the core of most current
      theories of its mechanisms of action. Although ethanol affects various
      biochemical processes such as neurotransmitter release, enzyme function, and ion
      channel kinetics, we are only beginning to understand the specific molecular
      sites to which ethanol molecules bind to produce these myriad effects. For most
      effects of ethanol characterized thus far, it is unknown whether the protein
      whose function is being studied actually binds ethanol, or if alcohol is instead
      binding to another protein that then indirectly affects the functioning of the
      protein being studied. In this Review, we describe criteria that should be
      considered when identifying alcohol binding sites and highlight a number of
      proteins for which there exists considerable molecular-level evidence for
      distinct ethanol binding sites.

PMID- 18632552
TI  - A new mouse mutant for the LDL receptor identified using ENU mutagenesis.
AB  - In an effort to discover new mouse models of cardiovascular disease using N-ethyl
      N-nitrosourea (ENU) mutagenesis followed by high-throughput phenotyping, we have
      identified a new mouse mutation, C699Y, in the LDL receptor (Ldlr), named wicked
      high cholesterol (WHC). When WHC was compared with the widely used Ldlr knockout
      (KO) mouse, notable phenotypic differences between strains were observed, such as
      accelerated atherosclerotic lesion formation and reduced hepatosteatosis in the
      ENU mutant after a short exposure to an atherogenic diet. This loss-of-function
      mouse model carries a single base mutation in the Ldlr gene on an otherwise pure
      C57BL/6J (B6) genetic background, making it a useful new tool for understanding
      the pathophysiology of atherosclerosis and for evaluating additional genetic
      modifiers regulating hyperlipidemia and atherogenesis. Further investigation of
      genomic differences between the ENU mutant and KO strains may reveal previously
      unappreciated sequence functionality.

PMID- 18632553
TI  - Naproxen-induced anemia and hypoalbuminemia in a 16-month-old child.

PMID- 18632554
TI  - Modular networks and cumulative impact of lateral transfer in prokaryote genome
      evolution.
AB  - Lateral gene transfer is an important mechanism of natural variation among
      prokaryotes, but the significance of its quantitative contribution to genome
      evolution is debated. Here, we report networks that capture both vertical and
      lateral components of evolutionary history among 539,723 genes distributed across
      181 sequenced prokaryotic genomes. Partitioning of these networks by an
      eigenspectrum analysis identifies community structure in prokaryotic gene-sharing
      networks, the modules of which do not correspond to a strictly hierarchical
      prokaryotic classification. Our results indicate that, on average, at least 81 +/
      15% of the genes in each genome studied were involved in lateral gene transfer
      at some point in their history, even though they can be vertically inherited
      after acquisition, uncovering a substantial cumulative effect of lateral gene
      transfer on longer evolutionary time scales.

PMID- 18632555
TI  - Conservation and topology of protein interaction networks under duplication
      divergence evolution.
AB  - Genomic duplication-divergence processes are the primary source of new protein
      functions and thereby contribute to the evolutionary expansion of functional
      molecular networks. Yet, it is still unclear to what extent such duplication
      divergence processes also restrict by construction the emerging properties of
      molecular networks, regardless of any specific cellular functions. We address
      this question, here, focusing on the evolution of protein-protein interaction
      (PPI) networks. We solve a general duplication-divergence model, based on the
      statistically necessary deletions of protein-protein interactions arising from
      stochastic duplications at various genomic scales, from single-gene to whole
      genome duplications. Major evolutionary scenarios are shown to depend on two
      global parameters only: (i) a protein conservation index (M), which controls the
      evolutionary history of PPI networks, and (ii) a distinct topology index (M')
      controlling their resulting structure. We then demonstrate that conserved,
      nondense networks, which are of prime biological relevance, are also necessarily
      scale-free by construction, irrespective of any evolutionary variations or
      fluctuations of the model parameters. It is shown to result from a fundamental
      linkage between individual protein conservation and network topology under
      general duplication-divergence evolution. By contrast, we find that conservation
      of network motifs with two or more proteins cannot be indefinitely preserved
      under general duplication-divergence evolution (independently from any network
      rewiring dynamics), in broad agreement with empirical evidence between
      phylogenetically distant species. All in all, these evolutionary constraints,
      inherent to duplication-divergence processes, appear to have largely controlled
      the overall topology and scale-dependent conservation of PPI networks, regardless
      of any specific biological function.

PMID- 18632556
TI  - Single treatment with RNAi against prion protein rescues early neuronal
      dysfunction and prolongs survival in mice with prion disease.
AB  - Prion diseases are fatal neurodegenerative conditions for which there is no
      effective treatment. Prion propagation involves the conversion of cellular prion
      protein, PrP(C), to its conformational isomer, PrP(Sc), which accumulates in
      disease. Here, we show effective therapeutic knockdown of PrP(C) expression using
      RNAi in mice with established prion disease. A single administration of
      lentivirus expressing a shRNA targeting PrP into each hippocampus of mice with
      established prion disease significantly prolonged survival time. Treated animals
      lived 19% and 24% longer than mice given an "empty" lentivirus, or not treated,
      respectively. Lentivirally mediated RNAi of PrP also prevented the onset of
      behavioral deficits associated with early prion disease, reduced spongiform
      degeneration, and protected against neuronal loss. In contrast, mice receiving
      empty virus or no treatment developed early cognitive impairment and showed
      severe spongiosis and neuronal loss. The focal use of RNAi therapeutically in
      prion disease further supports strategies depleting PrP(C), which we previously
      established to be a valid target for prion-based treatments. This approach can
      now be used to define the temporal, quantitative, and regional requirements for
      PrP knockdown for effective treatment of prion disease and to explore mechanisms
      involved in predegenerative neuronal dysfunction and its rescue.

PMID- 18632557
TI  - A germ-line-selective advantage rather than an increased mutation rate can
      explain some unexpectedly common human disease mutations.
AB  - Two nucleotide substitutions in the human FGFR2 gene (C755G or C758G) are
      responsible for virtually all sporadic cases of Apert syndrome. This condition is
      100-1,000 times more common than genomic mutation frequency data predict. Here,
      we report on the C758G de novo Apert syndrome mutation. Using data on older
      donors, we show that spontaneous mutations are not uniformly distributed
      throughout normal testes. Instead, we find foci where C758G mutation frequencies
      are 3-4 orders of magnitude greater than the remaining tissue. We conclude this
      nucleotide site is not a mutation hot spot even after accounting for possible
      Luria-Delbruck "mutation jackpots." An alternative explanation for such foci
      involving positive selection acting on adult self-renewing Ap spermatogonia
      experiencing the rare mutation could not be rejected. Further, the two youngest
      individuals studied (19 and 23 years old) had lower mutation frequencies and
      smaller foci at both mutation sites compared with the older individuals. This
      implies that the mutation frequency of foci increases as adults age, and thus
      selection could explain the paternal age effect for Apert syndrome and other
      genetic conditions. Our results, now including the analysis of two mutations in
      the same set of testes, suggest that positive selection can increase the relative
      frequency of premeiotic germ cells carrying such mutations, although individuals
      who inherit them have reduced fitness. In addition, we compared the anatomical
      distribution of C758G mutation foci with both new and old data on the C755G
      mutation in the same testis and found their positions were not correlated with
      one another.

PMID- 18632558
TI  - Listeria monocytogenes multidrug resistance transporters activate a cytosolic
      surveillance pathway of innate immunity.
AB  - To gain insight into the interaction of intracellular pathogens with host innate
      immune pathways, we performed an unbiased genetic screen of Listeria
      monocytogenes mutants that induced an enhanced or diminished host innate immune
      response. Here, we show that the major facilitator superfamily of bacterial
      multidrug resistance transporters (MDRs) controlled the magnitude of a host
      cytosolic surveillance pathway, leading to the production of several cytokines,
      including type I IFN. Mutations mapping to repressors of MDRs resulted in ectopic
      expression of their cognate transporters, leading to host responses that were
      increased up to 20-fold over wild-type bacteria, and a 20-fold decrease in
      bacterial growth in vivo. Mutation of one of the MDRs, MdrM, led to a 3-fold
      reduction in the IFN-beta response to L. monocytogenes infection, indicating a
      pivotal role for MdrM in activation of the host cytosolic surveillance system.
      Bacterial MDRs had previously been associated with resistance to antibiotics and
      other toxic compounds. This report links bacterial MDRs and host immunity.
      Understanding the mechanisms through which live pathogens activate innate immune
      signaling pathways should lead to the discovery of adjuvants, vaccines, and
      perhaps new classes of therapeutics. Indeed, we show that the mutants identified
      in this screen induced vastly altered type I IFN response in vivo as well.

PMID- 18632559
TI  - Soluble receptor-mediated selective inhibition of VEGFR and PDGFRbeta signaling
      during physiologic and tumor angiogenesis.
AB  - The simultaneous targeting of both endothelial cells and pericytes via inhibition
      of VEGF receptor (VEGFR) and PDGFbeta receptor (PDGFRbeta) signaling,
      respectively, has been proposed to enhance the efficacy of antiangiogenic tumor
      therapy. Clinical and preclinical modeling of combined VEGFR and PDGFRbeta
      signaling inhibition, however, has used small molecule kinase inhibitors with
      inherently broad substrate specificities, precluding detailed examination of this
      hypothesis. Here, adenoviral expression of a soluble VEGFR2/Flk1 ectodomain (Ad
      Flk1-Fc) in combination with a soluble ectodomain of PDGFRbeta (Ad sPDGFRbeta)
      allowed highly selective inhibition of these pathways. The activity of Ad
      sPDGFRbeta was validated in vitro against PDGF-BB and in vivo with near-complete
      blockade of pericyte recruitment in the angiogenic corpus luteum, resulting in
      prominent hemorrhage, thus demonstrating an essential function for PDGF signaling
      during ovarian angiogenesis. Combination therapy with Ad PDGFRbeta and submaximal
      doses of Ad Flk1-Fc produced modest additive antitumor effects; however, no
      additivity was observed with maximal VEGF inhibition in numerous s.c. models.
      Notably, VEGF inhibition via Ad Flk1-Fc was sufficient to strongly suppress tumor
      endothelial and pericyte content as well as intratumoral PDGF-B mRNA, obscuring
      additive Ad sPDGFRbeta effects on pericytes or tumor volume. These studies using
      highly specific soluble receptors suggest that additivity between VEGFR and
      PDGFRbeta inhibition depends on the strength of VEGF blockade and appears minimal
      under conditions of maximal VEGF antagonism.

PMID- 18632560
TI  - Host cell recognition by the henipaviruses: crystal structures of the Nipah G
      attachment glycoprotein and its complex with ephrin-B3.
AB  - Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic
      paramyxovirus genus Henipavirus, which can cause severe respiratory disease and
      fatal encephalitis infections in humans, with case fatality rates approaching
      75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein
      (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein
      that mediates membrane merger. The henipavirus G glycoproteins lack both
      hemagglutinating and neuraminidase activities and, instead, engage the highly
      conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors.
      Here, we report the crystal structures of the NiV-G both in its receptor-unbound
      state and in complex with ephrin-B3, providing, to our knowledge, the first view
      of a paramyxovirus attachment complex in which a cellular protein is used as the
      virus receptor. Complex formation generates an extensive protein-protein
      interface around a protruding ephrin loop, which is inserted in the central
      cavity of the NiV-G beta-propeller. Analysis of the structural data reveals the
      molecular basis for the highly specific interactions of the henipavirus G
      glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large
      ephrin family and suggests how they mediate in a unique fashion both cell
      attachment and the initiation of membrane fusion during the virus infection
      processes. The structures further suggest that the NiV-G/ephrin interactions can
      be effectively targeted to disrupt viral entry and provide the foundation for
      structure-based antiviral drug design.

PMID- 18632561
TI  - Interaction of nitric oxide with a functional model of cytochrome c oxidase.
AB  - Cytochrome c oxidase (CcO) is a multimetallic enzyme that carries out the
      reduction of O2 to H2O and is essential to respiration, providing the energy that
      powers all aerobic organisms by generating heat and forming ATP. The oxygen
      binding heme a(3) should be subject to fatal inhibition by chemicals that could
      compete with O2 binding. Near the CcO active site is another enzyme, NO synthase,
      which produces the gaseous hormone NO. NO can strongly bind to heme a(3), thus
      inhibiting respiration. However, this disaster does not occur. Using functional
      models for the CcO active site, we show how NO inhibition is avoided; in fact, it
      is found that NO can protect the respiratory enzyme from other inhibitors such as
      cyanide, a classic poison.

PMID- 18632562
TI  - Nitrite reductase activity of myoglobin regulates respiration and cellular
      viability in myocardial ischemia-reperfusion injury.
AB  - The nitrite anion is reduced to nitric oxide (NO*) as oxygen tension decreases.
      Whereas this pathway modulates hypoxic NO* signaling and mitochondrial
      respiration and limits myocardial infarction in mammalian species, the pathways
      to nitrite bioactivation remain uncertain. Studies suggest that hemoglobin and
      myoglobin may subserve a fundamental physiological function as hypoxia dependent
      nitrite reductases. Using myoglobin wild-type ((+/+)) and knockout ((-/-)) mice,
      we here test the central role of myoglobin as a functional nitrite reductase that
      regulates hypoxic NO* generation, controls cellular respiration, and therefore
      confirms a cytoprotective response to cardiac ischemia-reperfusion (I/R) injury.
      We find that myoglobin is responsible for nitrite-dependent NO* generation and
      cardiomyocyte protein iron-nitrosylation. Nitrite reduction to NO* by myoglobin
      dynamically inhibits cellular respiration and limits reactive oxygen species
      generation and mitochondrial enzyme oxidative inactivation after I/R injury. In
      isolated myoglobin(+/+) but not in myoglobin(-/-) hearts, nitrite treatment
      resulted in an improved recovery of postischemic left ventricular developed
      pressure of 29%. In vivo administration of nitrite reduced myocardial infarction
      by 61% in myoglobin(+/+) mice, whereas in myoglobin(-/-) mice nitrite had no
      protective effects. These data support an emerging paradigm that myoglobin and
      the heme globin family subserve a critical function as an intrinsic nitrite
      reductase that regulates responses to cellular hypoxia and reoxygenation
      [corrected]

PMID- 18632563
TI  - Interneuron activity controls endocannabinoid-mediated presynaptic plasticity
      through calcineurin.
AB  - Retrograde signaling by endocannabinoids (eCBs) mediates a widely expressed form
      of long-term depression at excitatory and inhibitory synapses (eCB-LTD),
      involving a reduction in neurotransmitter release. In the hippocampus, eCB-LTD
      occurs at interneuron (IN)-pyramidal cell (PC) synapses (I-LTD), and its
      induction requires a presynaptic reduction of cAMP/PKA signaling resulting from
      minutes of type 1 cannabinoid receptor (CB1R) activation. Although repetitive
      activity of glutamatergic synapses initiates the eCB mobilization required for I
      LTD, it is unclear whether CB1R-containing GABAergic terminals are passive
      targets of eCBs or whether they actively contribute to induction. Here, we show
      that the minutes-long induction period for I-LTD may serve as a window to
      integrate associated spontaneous activity in the same IN receiving the retrograde
      eCB signal. Indeed, reducing spontaneous IN firing blocked I-LTD, which could be
      rescued with extra stimulation of inhibitory afferents. Moreover, cell pair
      recordings showed that a single IN expressed LTD onto a PC only if it was active
      during eCB signaling. Several methods of disrupting presynaptic Ca(2+) dynamics
      all blocked I-LTD, strongly suggesting that IN spikes regulate I-LTD by raising
      Ca(2+) at the nerve terminal. Finally, inhibiting the Ca(2+)-activated
      phosphatase, calcineurin, fully blocked I-LTD, but blocking another phosphatase
      did not. Our findings support a model where both CB1R signaling and IN activity
      shift the balance of kinase and phosphatase activity in the presynaptic terminal
      to induce I-LTD.

PMID- 18632564
TI  - A modified cysteinyl-labeling assay reveals reversible oxidation of protein
      tyrosine phosphatases in angiomyolipoma cells.
AB  - The production of reactive oxygen species (ROS) exerts an additional tier of
      control over tyrosine phosphorylation-dependent signal transduction by
      transiently inhibiting the catalytic activity of specific protein tyrosine
      phosphatases (PTPs). Hence, the ability to detect reversible oxidation of PTPs in
      vivo is critical to understanding the complex biological role of ROS in the
      control of cellular signaling. Here, we describe an assay for identifying those
      PTPs that are reversibly oxidized in vivo, which utilizes the unique chemistry of
      the invariant catalytic Cys residue in labeling the active site with biotinylated
      small molecules under mildly acidic conditions. We have applied this cysteinyl
      labeling assay to the study of platelet-derived growth factor (PDGF) receptor
      signaling in an angiomyolipoma cell model. Doing so has allowed us to detect
      reversible oxidation of several proteins in response to sustained PDGF
      stimulation. As in other cell systems, we have observed the reversible oxidation
      of the classical PTP SHP2 and the tumor suppressor phosphatase PTEN in response
      to PDGF stimulation. Furthermore, we detected reversible oxidation of members of
      two other subclasses of PTPs, the receptor PTP LAR and the dual-specificity
      phosphatase MKP1. These data demonstrate the broad selectivity of the assay,
      allowing us to detect representatives of all of the major subgroups of the PTP
      superfamily. We anticipate that this cysteinyl-labeling enrichment strategy can
      be applied broadly to study reversible oxidation as a mechanism of harnessing PTP
      catalytic activity in a variety of signaling pathways.

PMID- 18632565
TI  - The capillarity picture and the kinetics of one-dimensional protein folding.

PMID- 18632566
TI  - The ancestral symbiont sensor kinase CSK links photosynthesis with gene
      expression in chloroplasts.
AB  - We describe a novel, typically prokaryotic, sensor kinase in chloroplasts of
      green plants. The gene for this chloroplast sensor kinase (CSK) is found in
      cyanobacteria, prokaryotes from which chloroplasts evolved. The CSK gene has
      moved, during evolution, from the ancestral chloroplast to the nuclear genomes of
      eukaryotic algae and green plants. The CSK protein is now synthesised in the
      cytosol of photosynthetic eukaryotes and imported into their chloroplasts as a
      protein precursor. In the model higher plant Arabidopsis thaliana, CSK is
      autophosphorylated and required for control of transcription of chloroplast genes
      by the redox state of an electron carrier connecting photosystems I and II. CSK
      therefore provides a redox regulatory mechanism that couples photosynthesis to
      gene expression. This mechanism is inherited directly from the cyanobacterial
      ancestor of chloroplasts, is intrinsic to chloroplasts, and is targeted to
      chloroplast genes.

PMID- 18632567
TI  - Circulating blood cells function as a surveillance system for damaged tissue in
      Drosophila larvae.
AB  - Insects have an open circulatory system in which the heart pumps blood
      (hemolymph) into the body cavity, where it directly bathes the internal organs
      and epidermis. The blood contains free and tissue-bound immune cells that
      function in the inflammatory response. Here, we use live imaging of transgenic
      Drosophila larvae with fluorescently labeled blood cells (hemocytes) to
      investigate the circulatory dynamics of larval blood cells and their response to
      tissue injury. We find that, under normal conditions, the free cells rapidly
      circulate, whereas the tissue-bound cells are sessile. After epidermal wounding,
      tissue-bound cells around the wound site remain sessile and unresponsive, whereas
      circulating cells are rapidly recruited to the site of damage by adhesive
      capture. After capture, these cells distribute across the wound, appear
      phagocytically active, and are subsequently released back into circulation by the
      healing epidermis. The results demonstrate that circulating cells function as a
      surveillance system that monitors larval tissues for damage, and that adhesive
      capture, an important mechanism of recruitment of circulating cells to
      inflammatory sites in vertebrates, is shared by insects and vertebrates despite
      the vastly different architectures of their circulatory systems.

PMID- 18632569
TI  - The RNA-binding proteins HYL1 and SE promote accurate in vitro processing of pri
      miRNA by DCL1.
AB  - The results of genetic studies in Arabidopsis indicate that three proteins, the
      RNase III DICER-Like1 (DCL1), the dsRNA-binding protein HYPONASTIC LEAVES1
      (HYL1), and the C2H2 Zn-finger protein SERRATE (SE), are required for the
      accurate processing of microRNA (miRNA) precursors in the plant cell nucleus. To
      elucidate the biochemical mechanism of miRNA processing, we developed an in vitro
      miRNA processing assay using purified recombinant proteins. We find that DCL1
      alone releases 21-nt short RNAs from dsRNA as well as synthetic miR167b precursor
      RNAs. However, correctly processed miRNAs constitute a minority of the cleavage
      products. We show that recombinant HYL1 and SE proteins accelerate the rate of
      DCL1-mediated cleavage of pre- and pri-miR167b substrates and promote accurate
      processing.

PMID- 18632570
TI  - Shifting transition states in the unfolding of a large ankyrin repeat protein.
AB  - The 33-amino-acid ankyrin motif comprises a beta-turn followed by two anti
      parallel alpha-helices and a loop and tandem arrays of the motif pack in a linear
      fashion to produce elongated structures characterized by short-range
      interactions. In this article we use site-directed mutagenesis to investigate the
      kinetic unfolding mechanism of D34, a 426-residue, 12-ankyrin repeat fragment of
      the protein ankyrinR. The data are consistent with a model in which the N
      terminal half of the protein unfolds first by unraveling progressively from the
      start of the polypeptide chain to form an intermediate; in the next step, the C
      terminal half of the protein unfolds via two pathways whose transition states
      have either the early or the late C-terminal ankyrin repeats folded. We conclude
      that the two halves of the protein unfold by different mechanisms because the N
      terminal moiety folds and unfolds in the context of a folded C-terminal moiety,
      which therefore acts as a "seed" and confers a unique directionality on the
      process, whereas the C-terminal moiety folds and unfolds in the context of an
      unfolded N-terminal moiety and therefore behaves like a single-domain ankyrin
      repeat protein, having a high degree of symmetry and consequently more than one
      unfolding pathway accessible to it.

PMID- 18632568
TI  - How vision begins: an odyssey.
AB  - Retinal rods and cones, which are the front-end light detectors in the eye,
      achieve wonders together by being able to signal single-photon absorption and yet
      also able to adjust their function to brightness changes spanning 10(9)-fold. How
      these cells detect light is now quite well understood. Not surprising for almost
      any biological process, the intial step of seeing reveals a rich complexity as
      the probing goes deeper. The odyssey continues, but the knowledge gained so far
      is already nothing short of remarkable in qualitative and quantitative detail. It
      has also indirectly opened up the mystery of odorant sensing. Basic science
      aside, clinical ophthalmology has benefited tremendously from this endeavor as
      well. This article begins by recapitulating the key developments in this
      understanding from the mid-1960s to the late 1980s, during which period the
      advances were particularly rapid and fit for an intricate detective story. It
      then highlights some details discovered more recently, followed by a comparison
      between rods and cones.

PMID- 18632571
TI  - Networking metabolites and diseases.

PMID- 18632572
TI  - Reconstituting plant miRNA biogenesis.

PMID- 18632573
TI  - Sterols in a unicellular relative of the metazoans.
AB  - Molecular clocks suggest that animals originated well before they first appear as
      macroscopic fossils, but geologic tests of these hypotheses have been elusive. A
      rare steroid hydrocarbon, 24-isopropylcholestane, has been hypothesized to be a
      biomarker for sponges or their immediate ancestors because of its relatively high
      abundance in pre-Ediacaran to Early Cambrian sedimentary rocks and oils. Biolipid
      precursors of this sterane have been reported to be prominent in several
      demosponges. Whether 24-isopropylcholestane can be interpreted as a sponge (and,
      hence, animal) biomarker, and so provide clues about early metazoan history,
      depends on an understanding of the distribution of sterol biosynthesis among
      animals and their protistan relatives. Accordingly, we characterized the sterol
      profile of the choanoflagellate Monosiga brevicollis, a representative of the
      unicellular sister group of animals. M. brevicollis does not produce a candidate
      sterol precursor for 24-isopropylcholestane under our experimental growth
      conditions. It does, however, produce a number of other sterols, and comparative
      genomics confirms its biosynthetic potential to produce the full suite of
      compounds recovered. Consistent with the phylogenetic position of
      choanoflagellates, the sterol profile and biosynthetic pathway of M. brevicollis
      display characteristics of both fungal and poriferan sterol biosynthesis. This is
      an example in which genomic and biochemical information have been used together
      to investigate the taxonomic specificity of a fossil biomarker.

PMID- 18632574
TI  - Genomic expression profiling of TNF-alpha-treated BDC2.5 diabetogenic CD4+ T
      cells.
AB  - TNF-alpha plays an important role in immune regulation, inflammation, and
      autoimmunity. Chronic TNF exposure has been shown to down-modulate T cell
      responses. In a mouse T cell hybridoma model, TNF attenuated T cell receptor
      (TCR) signaling. We have confirmed that chronic TNF and anti-TNF exposure
      suppressed and increased T cell responses, respectively. In adult TCR (BDC2.5)
      transgenic nonobese diabetic mice, DNA microarray analysis of global gene
      expression in BDC2.5 CD4(+) T cells in response to chronic TNF or anti-TNF
      exposure showed that genes involved in functional categories including T cell
      signaling, cell cycle, proliferation, ubiquitination, cytokine synthesis, calcium
      signaling, and apoptosis were modulated. Genes such as ubiquitin family genes,
      cytokine inducible Src homology 2-containing genes, cyclin-dependent kinase
      inhibitors p21, p57, calmodulin family genes (calmodulin-1, -2, and -3) and
      calcium channel voltage-dependent, N type alpha1B subunit (CaV2.2) were induced
      by TNF, whereas Vav2, Rho GTPase-activating protein, calcium channel voltage
      dependent, L type alpha1C subunit (CaV1.2), IL-1 receptor-associated kinase-1 and
      -2, and IL enhancer binding factor 3 were reduced by TNF. Genes such as CaV1.2
      and proliferating cell nuclear antigen, repressed by TNF, were induced by anti
      TNF treatment. Further, we showed that chronic TNF exposure impaired NF-kappaB
      and adaptor protein 1 transactivation activity, leading to T cell
      unresponsiveness. Thus, our results present a detailed picture of transcriptional
      programs affected by chronic TNF exposure and provide candidate target genes that
      may function to mediate TNF-induced T cell unresponsiveness.

PMID- 18632576
TI  - Kinetics of amorphous silica dissolution and the paradox of the silica
      polymorphs.
AB  - The mechanisms by which amorphous silica dissolves have proven elusive because
      noncrystalline materials lack the structural order that allows them to be studied
      by the classical terrace, ledge, kink-based models applied to crystals. This
      would seem to imply amorphous phases have surfaces that are disordered at an
      atomic scale so that the transfer of SiO(4) tetrahedra to solution always leaves
      the surface free energy of the solid unchanged. As a consequence, dissolution
      rates of amorphous phases should simply scale linearly with increasing driving
      force (undersaturation) through the higher probability of detaching silica
      tetrahedra. By examining rate measurements for two amorphous SiO(2) glasses we
      find, instead, a paradox. In electrolyte solutions, these silicas show the same
      exponential dependence on driving force as their crystalline counterpart, quartz.
      We analyze this enigma by considering that amorphous silicas present two
      predominant types of surface-coordinated silica tetrahedra to solution.
      Electrolytes overcome the energy barrier to nucleated detachment of higher
      coordinated species to create a periphery of reactive, lesser coordinated groups
      that increase surface energy. The result is a plausible mechanism-based model
      that is formally identical with the classical polynuclear theory developed for
      crystal growth. The model also accounts for reported demineralization rates of
      natural biogenic and synthetic colloidal silicas. In principle, these insights
      should be applicable to materials with a wide variety of compositions and
      structural order when the reacting units are defined by the energies of their
      constituent species.

PMID- 18632575
TI  - Genomic markers for malignant progression in pulmonary adenocarcinoma with
      bronchioloalveolar features.
AB  - Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC)
      without stromal, vascular, or pleural invasion, is considered an in situ tumor
      with a 100% survival rate. However, the histological criteria for invasion remain
      controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma,
      referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are
      considered to evolve from BAC, representing a paradigm for malignant progression
      in ADC. However, the supporting molecular evidence remains forthcoming. Here, we
      have studied the genomic changes of BAC and AWBF by array comparative genomic
      hybridization (CGH). We used submegabase-resolution tiling set array CGH to
      compare the genomic profiles of 14 BAC or BAC with focal area suspicious for
      invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring
      analysis found that genomic profiles of noninvasive and focally invasive BAC are
      indistinguishable and show fewer aberrations than tumor cells in BAC-like areas
      of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal
      regions. Increased genomic alterations were noted between BAC-like and invasive
      areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and
      were considered candidate marker genes for tumor invasion and progression.
      Correlative gene expression analyses demonstrated a high percentage of them to be
      poor prognosis markers in early stage ADC. Quantitative PCR also validated the
      amplification and overexpression of PDCD6 and TERT on chromosome 5p and the
      prognostic significance of PDCD6 in early stage ADC patients. We identified
      candidate genes that may be responsible for and are potential markers for
      malignant progression in AWBF.

PMID- 18632577
TI  - Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory
      receptor.
AB  - UL18 is a human cytomegalovirus class I MHC (MHCI) homolog that binds the host
      inhibitory receptor LIR-1 and the only known viral MHC homolog that presents
      peptides. The 2.2-A structure of a LIR-1/UL18/peptide complex reveals increased
      contacts and optimal surface complementarity in the LIR-1/UL18 interface compared
      with LIR/MHCI interfaces, resulting in a >1,000-fold higher affinity. Despite
      sharing only approximately 25% sequence identity, UL18's structure and peptide
      binding are surprisingly similar to host MHCI. The crystal structure suggests
      that most of the UL18 surface, except where LIR-1 and the host-derived light
      chain bind, is covered by carbohydrates attached to 13 potential N-glycosylation
      sites, thereby preventing access to bound peptide and association with most MHCI
      binding proteins. The LIR-1/UL18 structure demonstrates how a viral protein
      evolves from its host ancestor to impede unwanted interactions while preserving
      and improving its receptor-binding site.

PMID- 18632578
TI  - Replication stalling at unstable inverted repeats: interplay between DNA hairpins
      and fork stabilizing proteins.
AB  - DNA inverted repeats (IRs) are hotspots of genomic instability in both
      prokaryotes and eukaryotes. This feature is commonly attributed to their ability
      to fold into hairpin- or cruciform-like DNA structures interfering with DNA
      replication and other genetic processes. However, direct evidence that IRs are
      replication stall sites in vivo is currently lacking. Here, we show by 2D
      electrophoretic analysis of replication intermediates that replication forks
      stall at IRs in bacteria, yeast, and mammalian cells. We found that DNA hairpins,
      rather than DNA cruciforms, are responsible for the replication stalling by
      comparing the effects of specifically designed imperfect IRs with varying lengths
      of their central spacer. Finally, we report that yeast fork-stabilizing proteins,
      Tof1 and Mrc1, are required to counteract repeat-mediated replication stalling.
      We show that the function of the Tof1 protein at DNA structure-mediated stall
      sites is different from its previously described effect on protein-mediated
      replication fork barriers.

PMID- 18632579
TI  - Widespread spatial integration in primary somatosensory cortex.
AB  - Tactile discrimination depends on integration of information from the discrete
      receptive fields (RFs) of peripheral sensory afferents. Because this information
      is processed over a hierarchy of subcortical nuclei and cortical areas, the
      integration likely occurs at multiple levels. The current study presents results
      indicating that neurons across most of the extent of the hand representation in
      monkey primary somatosensory cortex (area 3b) interact, even when these neurons
      have separate RFs. We obtained simultaneous recordings by using a 100-electrode
      array implanted in the hand representation of primary somatosensory cortex of two
      anesthetized owl monkeys. During a series of 0.5-s skin indentations with single
      or dual probes, the distance between electrodes from which neurons with
      synchronized spike times were recorded exceeded 2 mm. The results provide
      evidence that stimuli on different parts of the hand influence the degree of
      synchronous firing among a large population of neurons. Because spike synchrony
      potentiates the activation of commonly targeted neurons, synchronous neural
      activity in primary somatosensory cortex can contribute to discrimination of
      complex tactile stimuli.

PMID- 18632580
TI  - CXCR4-CCR5: a couple modulating T cell functions.
AB  - Chemokines and their receptors direct leukocyte migration among blood, lymph and
      tissues. Evidence has recently accumulated that, besides their chemotactic
      functions, chemokine receptors are highly versatile players that fine tune immune
      responses. During human T cell activation by antigen-presenting cells, the
      chemokine receptors CCR5 and CXCR4 are recruited into the immunological synapse,
      where they deliver costimulatory signals. However, the molecular mechanisms
      allowing signaling versatility of chemokine receptors are unknown. Here, we
      describe the functional interaction between CXCR4 and CCR5 to exert specific
      biological functions and modulate T lymphocyte responses. We demonstrate that
      simultaneous expression and cooperation between CCR5 and CXCR4 are required for
      chemokine-induced T cell costimulation at the immunological synapse. In addition,
      we provide evidence for a physical association of the two receptors in a
      signaling complex that activates distinct T cell functions. We suggest that
      cooperation between receptors represents one key strategy for the functional
      plasticity of chemokines.

PMID- 18632581
TI  - The FHA domain proteins DAWDLE in Arabidopsis and SNIP1 in humans act in small
      RNA biogenesis.
AB  - Proteins containing the forkhead-associated domain (FHA) are known to act in
      biological processes such as DNA damage repair, protein degradation, and signal
      transduction. Here we report that DAWDLE (DDL), an FHA domain-containing protein
      in Arabidopsis, acts in the biogenesis of miRNAs and endogenous siRNAs. Unlike
      mutants of genes known to participate in the processing of miRNA precursors, such
      as dcl1, hyponastic leaves1, and serrate, ddl mutants show reduced levels of pri
      miRNAs as well as mature miRNAs. Promoter activity of MIR genes, however, is not
      affected by ddl mutations. DDL is an RNA binding protein and is able to interact
      with DCL1. In addition, we found that SNIP1, the human homolog of DDL, is
      involved in miRNA biogenesis and interacts with Drosha. Therefore, we uncovered
      an evolutionarily conserved factor in miRNA biogenesis. We propose that DDL
      participates in miRNA biogenesis by facilitating DCL1 to access or recognize pri
      miRNAs.

PMID- 18632582
TI  - Fc receptor engagement mediates differentiation of cardiac fibroblast precursor
      cells.
AB  - We previously described a critical role for a fibroblast precursor population in
      the development of a murine fibrotic cardiomyopathy model (I/RC). These
      precursors arose from circulating bone marrow-derived cells of monocytic origin.
      Administration of serum amyloid P (SAP) prevented the presence of this cell
      population in the heart and the cardiomyopathy. Because SAP binds to Fc receptors
      (FcRs) expressed on monocytes, we investigated the involvement of FcR signaling.
      We chose mice lacking the FcRgamma chain protein (FcRgamma(-/-)), a common
      membrane-signaling component of activating FcRs. Like wild-type mice, FcRgamma(-/
      ) mice developed fibrosis and cardiac dysfunction when subjected to I/RC.
      However, unlike wild-type mice, SAP in FcRgamma(-/-) mice failed to inhibit the
      development of fibrosis and cardiac dysfunction and did not diminish the numbers
      of alpha-smooth muscle actin(+) and CD34(+), CD45(+) fibroblasts that were
      typical for I/RC. To further examine the role of SAP in monocyte-to-fibroblast
      transition, we performed in vitro assays in which human peripheral blood
      mononuclear cells (PBMCs) migrated through human umbilical vein endothelial cells
      (HUVECs). We found that MCP-1-dependent transendothelial migration of monocytes
      markedly accelerated their differentiation into fibroblasts. This monocyte
      differentiation to fibroblasts was eliminated when SAP was added to the PBMC
      suspension before endothelial transmigration. Adding SAP to cells after
      successful migration did not inhibit fibroblast maturation. These data indicate
      that SAP inhibits the differentiation of a blood-borne, myeloid cell population
      into fibroblasts by signaling through activating FcRs before transendothelial
      migration has occurred. We suggest that FcR activation of circulating precursor
      cells may represent a new treatment target for adverse remodeling and cardiac
      fibrosis.

PMID- 18632583
TI  - Hidden copy number variation in the HapMap population.
AB  - Recently, the extent of copy number variation (CNV) throughout the genome has
      been shown to be far greater than previously thought. Further, it has been
      demonstrated that specific copy number variable regions (CNVRs) are associated
      with particular diseases, suggesting that these genetic variations may have an
      important biological role. Hence, calling CNVRs and subsequently classifying
      samples as "losses" or "gains" is of great interest. A number of papers have been
      published containing classifications of CNVs, and here we show how the presence
      of pedigree information can be used for assessing the performance of those
      classification methods. In this article, by examining CNV classifications made in
      the HapMap samples, we show that estimates of the number of false-positive
      classifications per individual made by current approaches can be determined.
      Moreover, commonplace technologies for determining the locations of CNVRs
      aggregate information across the maternal and paternal chromosomes at the locus
      of interest. Here, we show that copy number variation on each chromosome can be
      inferred and, in particular, we discuss the existence of a class of CNVs that are
      inevitably misclassified and give an estimate of their prevalence. Although our
      focus is not on the development of calling algorithms per se, we describe and
      provide an example of how our model might be incorporated into the initial
      classification procedure to produce more robust results. Finally, we discuss how
      this methodology might be applied to future studies to obtain better estimates of
      the extent of CNV across the genome.

PMID- 18632584
TI  - A beta alpha-barrel built by the combination of fragments from different folds.
AB  - Combinatorial assembly of protein domains plays an important role in the
      evolution of proteins. There is also evidence that protein domains have come
      together from stable subdomains. This concept of modular assembly could be used
      to construct new well folded proteins from stable protein fragments. Here, we
      report the construction of a chimeric protein from parts of a (betaalpha)(8)
      barrel enzyme from histidine biosynthesis pathway (HisF) and a protein of the
      (betaalpha)(5)-flavodoxin-like fold (CheY) from Thermotoga maritima that share a
      high structural similarity. We expected this construct to fold into a full
      (betaalpha)(8)-barrel. Our results show that the chimeric protein is a stable
      monomer that unfolds with high cooperativity. Its three-dimensional structure,
      which was solved to 3.1 A resolution by x-ray crystallography, confirms a barrel
      like fold in which the overall structures of the parent proteins are highly
      conserved. The structure further reveals a ninth strand in the barrel, which is
      formed by residues from the HisF C terminus and an attached tag. This strand
      invades between beta-strand 1 and 2 of the CheY part closing a gap in the
      structure that might be due to a suboptimal fit between the fragments. Thus, by a
      combination of parts from two different folds and a small arbitrary fragment, we
      created a well folded and stable protein.

PMID- 18632585
TI  - Two isozymes of particulate methane monooxygenase with different methane
      oxidation kinetics are found in Methylocystis sp. strain SC2.
AB  - Methane-oxidizing bacteria (methanotrophs) attenuate methane emission from major
      sources, such as wetlands, rice paddies, and landfills, and constitute the only
      biological sink for atmospheric methane in upland soils. Their key enzyme is
      particulate methane monooxygenase (pMMO), which converts methane to methanol. It
      has long been believed that methane at the trace atmospheric mixing ratio of 1.75
      parts per million by volume (ppmv) is not oxidized by the methanotrophs cultured
      to date, but rather only by some uncultured methanotrophs, and that type I and
      type II methanotrophs contain a single type of pMMO. Here, we show that the type
      II methanotroph Methylocystis sp. strain SC2 possesses two pMMO isozymes with
      different methane oxidation kinetics. The pmoCAB1 genes encoding the known type
      of pMMO (pMMO1) are expressed and pMMO1 oxidizes methane only at mixing ratios
      >600 ppmv. The pmoCAB2 genes encoding pMMO2, in contrast, are constitutively
      expressed, and pMMO2 oxidizes methane at lower mixing ratios, even at the trace
      level of atmospheric methane. Wild-type strain SC2 and mutants expressing pmoCAB2
      but defective in pmoCAB1 consumed atmospheric methane for >3 months. Growth
      occurred at 10-100 ppmv methane. Most type II but no type I methanotrophs possess
      the pmoCAB2 genes. The apparent K(m) of pMMO2 (0.11 muM) in strain SC2
      corresponds well with the K(m(app)) values for methane oxidation measured in
      soils that consume atmospheric methane, thereby explaining why these soils are
      dominated by type II methanotrophs, and some by Methylocystis spp., in
      particular. These findings change our concept of methanotroph ecology.

PMID- 18632586
TI  - Long-term functional evolution after an acute kidney injury: a 10-year study.
AB  - BACKGROUND: Data on long-term effects of acute kidney injury (AKI) on renal
      function (RF) are scarce and factors implicated in the functional outcome are not
      established. Our aim was to investigate these aspects. METHODS: At hospital
      discharge and annually for 10 years, we retrospectively reviewed RF of 187
      patients surviving AKI. Glomerular filtration rates estimated with MDRD equation
      (eGFR) and KDOQI stages were used to evaluate RF. Only 34.8% of patients had pre
      existing renal dysfunction (KDOQI-3). Variables determining long-term RF were
      collected during AKI and at discharge and analysed with a regression model.
      RESULTS: At discharge no patient necessitated dialysis, but eGFR was lower than
      baseline (47.5 +/- 23.3 ml/min/ 1.73 m(2) versus 75.8 +/- 25.4 ml/min/1.73 m(2));
      38.4% of survivors had recovered basal RF: 26% of those with previous normal RF
      and 61% of those in KDOQI-3, respectively. At 1 year, eGFR increased to 61.9 +/-
      24.4 ml/min/1.73 m(2) and remained stable later. During an 8-year median follow
      up (P25:2; P75:10), 31% improved RF, 50% remained stable and 19% deteriorated. In
      total only 46% (n = 82) definitively recovered RF. Finally, at the end of the
      study period 61.6% presented some degree of renal dysfunction: 40% of those with
      previous normal RF developed moderate-severe renal dysfunction and 37% KDOQI-3
      progressed into more severe renal failure. Only two patients needed dialysis.
      Regression model identified age, co-morbidities, discharge eGFR and follow-up
      time as independent predictors of long-term RF. CONCLUSIONS: AKI carries
      implication for long-term RF even in patients without pre-existing renal
      dysfunction. Ageing, co-morbidities and RF at discharge are determinants of the
      long-term functional outcome.

PMID- 18632587
TI  - The clinical course of steroid-sensitive childhood nephrotic syndrome is
      associated with a functional IL12B promoter polymorphism.
AB  - BACKGROUND: Steroid-sensitive nephrotic syndrome (NS) of childhood is the most
      common glomerular disease in children. The type and duration of response to
      corticosteroid therapy are used for clinical classification, and especially
      patients with steroid dependence often have a complicated course, requiring
      intensified immunosuppressive treatment. Its cause is still unknown although a
      cytokine-mediated course of disease has been implicated. Interleukin 12 (IL-12)
      is critical in determining the type of immune response. The ability of dendritic
      cells to secrete bioactive IL-12 is associated with a bi-allelic polymorphism
      within the promoter region of IL12B, the gene encoding the IL-12 p40 subunit. We
      hypothesized that this genotype may be involved in steroid-sensitive INS.
      METHODS: Using allele-specific PCR, 79 children with relapsing NS were genotyped
      for the IL12Bpro polymorphism, and genotype was correlated with clinical
      phenotype (presence/absence of steroid dependence). RESULTS: Children with the
      steroid-dependent course are at a significantly higher frequency homozygous for
      one IL12B allele compared to children without steroid dependence (46.7% and
      17.6%, respectively). This genotype has previously been shown to be associated
      with impaired IL-12 secretion. CONCLUSION: Polymorphisms in the IL12B promoter
      region associate with two different clinical courses of NS. The IL12Bpro
      polymorphism may therefore define molecular subgroups with different prognosis.
      Further studies are needed to evaluate the prognostic value.

PMID- 18632588
TI  - Stepwise increase in the prevalence of isolated systolic hypertension with the
      stages of chronic kidney disease.
AB  - BACKGROUND: Hypertension is common in patients with chronic kidney disease (CKD),
      and isolated systolic hypertension (ISH) accounts for most patients with
      inadequate blood pressure (BP) control. However, it remains unclear whether the
      prevalence of ISH would increase with the advancement of CKD. METHODS: CKD
      patients of stages 3, 4 and 5 were recruited (n = 324). Based on office systolic
      BP (SBP) and diastolic BP (DBP), they were classified into any of the four
      hypertensive subtypes: normotension (SBP/DBP <140/90 mmHg), isolated diastolic
      hypertension (IDH, SBP <140 mmHg and DBP >or=90 mmHg), ISH (SBP >or=140 mmHg and
      DBP <90 mmHg) and systolic-diastolic hypertension (SDH, SBP/DBP >or=140/90 mmHg).
      RESULTS: The control rate was 45.7% at stage 3, which decreased with the
      advancement of CKD (control rate was 51.9%, 40.4% and 38.6% in stage 3, 4 and 5,
      respectively; P < 0.05). The prevalence of IDH changed from 5.0% to 5.3% and 0%
      from stage 3 to 4 and 5, while there was no significant change in the prevalence
      of SDH (15.0%, 14.9% and 15.7% at stage 3, 4 and 5, respectively). There was a
      stepwise increase in the prevalence of ISH with the stages of CKD (it was 28.1%,
      39.4% and 45.7% in stage 3, 4 and 5, respectively). Logistic regression showed
      that age and CKD stages [compared with stage 3, stage 4 and 5 had 2.57 (95% CI
      1.04-6.33) and 3.68 (95% CI 1.09-12.47) folds higher risk to develop ISH,
      respectively] were independent predictors of ISH. CONCLUSION: The prevalence of
      ISH increased correspondingly with advanced stages of CKD, which may partially
      contribute to the increased cardiovascular mortality during the progress of CKD.

PMID- 18632589
TI  - The emerging biology of adipose tissue in chronic kidney disease: from fat to
      facts.

PMID- 18632590
TI  - AA amyloidosis due to chronic oxalate arthritis and vasculitis in a patient with
      secondary oxalosis after jejunoileal bypass surgery.
AB  - We report a case of a woman with secondary oxalosis after jejunoileal bypass
      surgery for obesity, who presented with oxalate stone disease and renal
      insufficiency requiring dialysis. Thirty years after surgery, longstanding
      osteoarticular symptoms were recognized as oxalate arthritis. Eventually, she
      also developed oxalate vasculitis, which improved with corticoid treatment and
      intensification of dialysis. Work-up for kidney transplantation revealed AA
      amyloidosis on gastric and colonic biopsies. Since no other cause of chronic
      inflammation could be identified, it was concluded that the amyloidosis was
      secondary to oxalate arthritis and vasculitis. To our knowledge, this is the
      first report on this association.

PMID- 18632591
TI  - The impact of automated eGFR reporting and education on nephrology service
      referrals.
AB  - BACKGROUND: Serum creatinine concentration is an unreliable and insensitive
      marker of chronic kidney disease (CKD). To improve CKD detection, the
      Australasian Creatinine Consensus Working Committee recommended reporting of
      estimated glomerular filtration rate (eGFR) using the four-variable Modification
      of Diet in Renal Disease (MDRD) formula with every request for serum creatinine
      concentration. The aim of this study was to evaluate the impact of automated
      laboratory reporting of eGFR on the quantity and quality of referrals to
      nephrology services in Southeast Queensland, Australia. METHODS: Outpatient
      referrals to a tertiary and regional renal service, and a single private practice
      were prospectively audited over 3-12 months prior to and 12 months following the
      introduction of automated eGFR reporting and concomitant clinician education. The
      appropriateness of referrals to a nephrologist was assessed according to the
      Kidney Check Australia Taskforce (KCAT) criteria. Significant changes in the
      quantity and/or quality of referrals over time were analysed by exponentially
      weighed moving average (EWMA) charts with control limits based on +/-3 standard
      deviations. RESULTS: A total of 1019 patients were referred to the centres during
      the study period. Monthly referrals overall increased by 40% following the
      introduction of eGFR reporting, and this was most marked for the tertiary renal
      service (52% above baseline). The appropriateness of nephrologist referrals, as
      adjudicated by the KCAT criteria, fell significantly from 74.3% in the 3 months
      pre-eGFR reporting to 65.2% in the 12 months thereafter (P < 0.05). Nevertheless,
      a greater absolute number of CKD patients were appropriately being referred for
      nephrologist review in the post-eGFR period (24 versus 15 per month). Patients
      referred following the introduction of eGFR were significantly more likely to be
      older (median 63.2 versus 59.3 years, P < 0.05), diabetic (25 versus 18%, P =
      0.05) and have stage 3 CKD (48% versus 36%, P < 0.01). CONCLUSION: The
      introduction of automated eGFR calculation has led to an overall increase in
      referrals with a small but significant decrease in referral quality. The increase
      in referrals was seen predominantly in older and diabetic patients with stage 3
      CKD and appeared to result in net benefit.

PMID- 18632592
TI  - A cautionary note on the evaluation of biomarkers of subtypes of a single
      disease.
AB  - Heterogeneity in the molecular characteristics of a disease presents a challenge
      to investigators attempting to identify biomarkers of the disease. Preceding the
      biomarker discovery effort with stratification within a heterogeneous disease
      group, which amounts to grouping disease cases into more homogeneous subtypes,
      seems to be a natural strategy for discovering subtype-specific biomarkers. This
      is because biologically more homogeneous subgroups are presumably easier to
      distinguish from the nondiseased than the entire heterogeneous disease group. The
      misleading benefits of this two-step approach are illustrated using an example
      from a protein biomarker discovery project for breast cancer. A potential
      analytical pitfall in this framework is explained using a conditional probability
      argument.

PMID- 18632593
TI  - 15-prostaglandin dehydrogenase expression alone or in combination with ACSM1
      defines a subgroup of the apocrine molecular subtype of breast carcinoma.
AB  - Established histopathological criteria divide invasive breast carcinomas into
      defined groups. Ductal of no specific type and lobular are the two major subtypes
      accounting for around 75 and 15% of all cases, respectively. The remaining 10%
      include rarer types such as tubular, cribriform, mucinous, papillary, medullary,
      metaplastic, and apocrine breast carcinomas. Molecular profiling technologies, on
      the other hand, subdivide breast tumors into five subtypes, basal-like, luminal
      A, luminal B, normal breast tissue-like, and ERBB2-positive, that have different
      prognostic characteristics. An additional subclass termed "molecular apocrine"
      has recently been described, but these lesions did not exhibit all the
      histopathological features of classical invasive apocrine carcinomas (IACs). IACs
      make up 0.5-3% of the invasive ductal carcinomas, and despite the fact that they
      are morphologically distinct from other breast lesions, there are presently no
      standard molecular criteria available for their diagnosis and as a result no
      precise information as to their prognosis. Toward this goal our laboratories have
      embarked in a systematic proteomics endeavor aimed at identifying biomarkers that
      may characterize and subtype these lesions as well as targets that may lead to
      the development of novel targeted therapies and chemoprevention strategies. By
      comparing the protein expression profiles of apocrine macrocysts and non
      malignant breast epithelial tissue we have previously reported the identification
      of a few proteins that are specifically expressed by benign apocrine lesions as
      well as by the few IACs that were available to us at the time. Here we reiterate
      our strategy to reveal apocrine cell markers and present novel data, based on the
      analysis of a considerably larger number of samples, establishing that IACs
      correspond to a distinct molecular subtype of breast carcinomas characterized by
      the expression of 15-prostaglandin dehydrogenase alone or in combination with a
      novel form of acyl-CoA synthetase medium-chain family member 1 (ACSM1). Moreover
      we show that 15-prostaglandin dehydrogenase is not expressed by other breast
      cancer types as determined by gel-based proteomics and immunohistochemistry
      analysis and that antibodies against this protein can identify IACs in an
      unbiased manner in a large breast cancer tissue microarray making them
      potentially useful as a diagnostic aid.

PMID- 18632594
TI  - Comparative proteomics study reveals that bacterial CpG motifs induce tumor cell
      autophagy in vitro and in vivo.
AB  - Unmethylated CpG dinucleotides, present in bacterial DNA, are recognized in
      vertebrates via the Toll-like receptor 9 (TLR9) and are known to act as an
      anticancer agent by stimulating immune cells to induce a proinflammatory
      response. Although the effects of CpG-oligodeoxynucleotides (CpG-ODNs) in immune
      cells have been widely studied, little is known regarding their molecular effects
      in TLR9-positive tumor cells. To better understand the role of these bacterial
      motifs in cancer cells, we analyzed proteome modifications induced in TLR9
      positive tumor cells in vitro and in vivo after CpG-ODN treatment in a rat colon
      carcinoma model. Proteomics analysis of tumor cells by two-dimensional gel
      electrophoresis followed by mass spectrometry identified several proteins
      modulated by bacterial CpG motifs. Among them, several are related to autophagy
      including potential autophagic substrates. In addition, we observed an increased
      glyceraldehyde-3-phosphate dehydrogenase expression, which has been shown to be
      sufficient to trigger an autophagic process. Autophagy is a self-digestion
      pathway whereby cytoplasmic material is sequestered by a structure termed the
      autophagosome for subsequent degradation and recycling. As bacteria are known to
      trigger autophagy, we assessed whether bacterial CpG motifs might induce
      autophagy in TLR9-positive tumor cells. We showed that CpG-ODN can induce
      autophagy in rodent and human tumor cell lines and was TLR9-dependent. In
      addition, an increase in the number of autophagosomes can also be observed in
      vivo after CpG motif intratumoral injection. Our findings bring new insights on
      the effect of bacterial CpG motifs in tumor cells and may be relevant for cancer
      treatment and more generally for gene therapy approaches in TLR9-positive
      tissues.

PMID- 18632595
TI  - Enhanced detection of low abundance human plasma proteins using a tandem IgY12
      SuperMix immunoaffinity separation strategy.
AB  - The enormous dynamic range of human bodily fluid proteomes poses a significant
      challenge for current MS-based proteomics technologies as it makes it especially
      difficult to detect low abundance proteins in human biofluids such as blood
      plasma, which is an essential aspect for successful biomarker discovery efforts.
      Here we present a novel tandem IgY12-SuperMix immunoaffinity separation system
      for enhanced detection of low abundance proteins in human plasma. The tandem
      IgY12-SuperMix system separates approximately 60 abundant proteins from the low
      abundance proteins in plasma, allowing for significant enrichment of low
      abundance plasma proteins in the SuperMix flow-through fraction. High
      reproducibility of the tandem separations was observed in terms of both sample
      processing recovery and LC-MS/MS identification results based on spectral count
      data. The ability to quantitatively measure differential protein abundances
      following application of the tandem separations was demonstrated by spiking six
      non-human standard proteins at three different levels into plasma. A side-by-side
      comparison between the SuperMix flow-through and IgY12 flow-through samples
      analyzed by both one- and two-dimensional LC-MS/MS revealed a 60-80% increase in
      proteome coverage as a result of the SuperMix separations, suggesting
      significantly enhanced detection of low abundance proteins. A total of 695 plasma
      proteins were confidently identified in a single analysis (with a minimum of two
      peptides per protein) by coupling the tandem separation strategy with two
      dimensional LC-MS/MS, including 42 proteins with reported normal concentrations
      of approximately 100 pg/ml to 100 ng/ml. The concentrations of two selected
      proteins, macrophage colony-stimulating factor 1 and matrix metalloproteinase-8,
      were independently validated by ELISA as 202 pg/ml and 12.4 ng/ml, respectively.
      Evaluation of binding efficiency revealed that 45 medium abundance proteins were
      efficiently captured by the SuperMix column with >90% retention. Taken together,
      these results illustrate the potential broad utilities of this tandem IgY12
      SuperMix strategy for proteomics applications involving human biofluids where
      effectively addressing the dynamic range challenge of the specimen is imperative.

PMID- 18632596
TI  - Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat
      hearts and neonatal cardiomyocytes.
AB  - AIMS: The objective of this study was to investigate whether a cytoprotective
      herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial
      effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND
      RESULTS: Primary cultured neonatal rat cardiomyocytes were treated with the
      vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus
      doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed
      Bcl-2 family protein balance, disrupted mitochondrial membrane potential,
      precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell
      death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment
      suppressed all the actions of doxorubicin. Similarly, rats treated with
      doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day]
      displayed retarded growth of body and heart as well as elevated apoptotic indexes
      in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment
      (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the
      aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION:
      Doxorubicin impairs viability of cardiomyocytes at least partially by activating
      the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can
      effectively and extensively counteract this action of doxorubicin, and may
      potentially protect the heart from the severe toxicity of doxorubicin.

PMID- 18632597
TI  - Refractoriness to antivascular endothelial growth factor treatment: role of
      myeloid cells.
AB  - CD11b+Gr1+ cells, which include neutrophils, macrophages, and myeloid-derived
      suppressor cells, have been shown to contribute to tumor angiogenesis. Recently,
      we found that accumulation of CD11b+Gr1+ in tumors renders them refractory to
      angiogenic blockade by vascular endothelial growth factor (VEGF) antibodies. This
      effect was traced to a pathway of CD11b+Gr1+-mediated angiogenesis that is, at
      least in part, driven by the secreted protein Bv8, which is up-regulated by the
      important myeloid growth factor granulocyte colony-stimulating factor (G-CSF).
      Thus, G-CSF may promote tumor angiogenesis through a Bv8-dependent pathway that
      bypasses VEGF and renders tumors refractory to anti-VEGF therapy.

PMID- 18632598
TI  - Cell competition and its possible relation to cancer.
AB  - Cell competition can occur when cells of different genotypes share the same
      developing compartment, with one genotype displacing the other as a result of a
      proliferative advantage. Studies of cell competition in Drosophila have
      identified an active process of cell assassination and corpse engulfment, and
      also roles for Myc and the Warts/Hippo tumor suppressor pathway. Here, we discuss
      the possible relevance of cell competition to cancer.

PMID- 18632599
TI  - Rethinking brain tumors: the fourth Mouse Models of Human Cancers Consortium
      nervous system tumors workshop.

PMID- 18632600
TI  - XXIII International Association for Comparative Research on Leukemia and Related
      Diseases Symposium: from molecular pathogenesis to targeted therapy in leukemia
      and solid tumors.

PMID- 18632601
TI  - A novel therapeutic combination using PD 0332991 and bortezomib: study in the
      5T33MM myeloma model.
AB  - Multiple myeloma (MM) remains incurable partly because no effective cell cycle
      based therapy has been available to both control tumor cell proliferation and
      synergize with cytotoxic killing. PD 0332991 is an orally active small molecule
      that potently and specifically inhibits Cdk4 and Cdk6. It has been shown to
      induce rapid G(1) cell cycle arrest in primary human myeloma cells and suppress
      tumor growth in xenograft models. To improve therapeutic targeting of myeloma
      progression, we combined tumor suppression by PD 0332991 with cytotoxic killing
      by bortezomib, a proteasome inhibitor widely used in myeloma treatment, in the
      immunocompetent 5T33MM myeloma model. We show that 5T33MM tumor cells proliferate
      aggressively in vivo due to expression of cyclin D2, elevation of Cdk4, and
      impaired p27(Kip1) expression, despite inhibition of Cdk4/6 by p18(INK4c) and the
      maintenance of a normal plasma cell transcription program. PD 0332991 potently
      inhibits Cdk4/6-specific phosphorylation of Rb and cell cycle progression through
      G(1) in aggressively proliferating primary 5T33MM cells, in vivo and ex vivo.
      This leads to tumor suppression and a significant improvement in survival.
      Moreover, induction of G(1) arrest by PD 0332991 sensitizes 5T33MM tumor cells to
      killing by bortezomib. Inhibition of Cdk4/6 by PD 0332991, therefore, effectively
      controls myeloma tumor expansion and sensitizes tumor cells to bortezomib killing
      in the presence of an intact immune system, thereby representing a novel and
      promising cell cycle-based combination therapy.

PMID- 18632603
TI  - Monitoring serial changes in circulating human breast cancer cells in murine
      xenograft models.
AB  - Circulating tumor cells (CTC) are emerging as a powerful prognostic and
      predictive biomarker in several types of cancer, including breast, colon, and
      prostate. Studies of CTC in metastasis and further development of CTC as a
      biomarker in cancer have been limited by the inability to repetitively monitor
      CTC in mouse models of cancer. We have validated a method to enumerate CTC in
      blood samples obtained from living mice using a modified version of an in vitro
      diagnostic system for quantifying CTC in patients. Different routes of blood
      collection were tested to identify a method to reproducibly recover CTC from
      tumor-bearing mice without interference from contaminating normal murine
      epithelial cells. CTC are present in blood samples from mice bearing orthotopic
      xenografts of several different breast cancer cell lines and primary breast
      cancer cells from patient biopsies. We also show that this technology can be used
      for serial monitoring of CTC in mouse xenograft models of human breast cancer.
      These results establish a new method for studying CTC in mouse models of
      epithelial cancer, providing the foundation for studies of molecular regulation
      of CTC in cancer and CTC as biomarker for therapeutic efficacy.

PMID- 18632602
TI  - Novel MEK1 mutation identified by mutational analysis of epidermal growth factor
      receptor signaling pathway genes in lung adenocarcinoma.
AB  - Genetic lesions affecting a number of kinases and other elements within the
      epidermal growth factor receptor (EGFR) signaling pathway have been implicated in
      the pathogenesis of human non-small-cell lung cancer (NSCLC). We performed
      mutational profiling of a large cohort of lung adenocarcinomas to uncover other
      potential somatic mutations in genes of this pathway that could contribute to
      lung tumorigenesis. We have identified in 2 of 207 primary lung tumors a somatic
      activating mutation in exon 2 of MEK1 (i.e., mitogen-activated protein kinase
      kinase 1 or MAP2K1) that substitutes asparagine for lysine at amino acid 57
      (K57N) in the nonkinase portion of the kinase. Neither of these two tumors
      harbored known mutations in other genes encoding components of the EGFR signaling
      pathway (i.e., EGFR, HER2, KRAS, PIK3CA, and BRAF). Expression of mutant, but not
      wild-type, MEK1 leads to constitutive activity of extracellular signal-regulated
      kinase (ERK)-1/2 in human 293T cells and to growth factor-independent
      proliferation of murine Ba/F3 cells. A selective MEK inhibitor, AZD6244, inhibits
      mutant-induced ERK activity in 293T cells and growth of mutant-bearing Ba/F3
      cells. We also screened 85 NSCLC cell lines for MEK1 exon 2 mutations; one line
      (NCI-H1437) harbors a Q56P substitution, a known transformation-competent allele
      of MEK1 originally identified in rat fibroblasts, and is sensitive to treatment
      with AZD6244. MEK1 mutants have not previously been reported in lung cancer and
      may provide a target for effective therapy in a small subset of patients with
      lung adenocarcinoma.

PMID- 18632604
TI  - Tissue-specific promoters active in CD44+CD24-/low breast cancer cells.
AB  - It has been proposed that human tumors contain stem cells that have a central
      role in tumor initiation and posttreatment relapse. Putative breast cancer stem
      cells may reside in the CD44(+)CD24(-/low) population. Oncolytic adenoviruses are
      attractive for killing of these cells because they enter through infection and
      are therefore not susceptible to active and passive mechanisms that render stem
      cells resistant to many drugs. Although adenoviruses have been quite safe in
      cancer trials, preclinical work suggests that toxicity may eventually be possible
      with more active agents. Therefore, restriction of virus replication to target
      tissues with tissues-specific promoters is appealing for improving safety and can
      be achieved without loss of efficacy. We extracted CD44(+)CD24(-/low) cells from
      pleural effusions of breast cancer patients and found that modification of
      adenovirus type 5 tropism with the serotype 3 knob increased gene delivery to
      CD44(+)CD24(-/low) cells. alpha-Lactalbumin, cyclo-oxygenase 2, telomerase, and
      multidrug resistance protein promoters were studied for activity in CD44(+)CD24(
      /low) cells, and a panel of oncolytic viruses was subsequently constructed. Each
      virus featured 5/3 chimerism of the fiber and a promoter controlling expression
      of E1A, which was also deleted in the Rb binding domain for additional tumor
      selectivity. Cell killing assays identified Ad5/3-cox2L-d24 and Ad5/3-mdr-d24 as
      the most active agents, and these viruses were able to completely eradicate
      CD44(+)CD24(-/low) cells in vitro. In vivo, these viruses had significant
      antitumor activity in CD44(+)CD24(-/low)-derived tumors. These findings may have
      relevance for elimination of cancer stem cells in humans.

PMID- 18632605
TI  - Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17
      92 microRNA cluster.
AB  - MicroRNAs (miRNAs) are a distinct class of small noncoding RNAs that
      posttranscriptionally repress expression of target genes through imperfect base
      pairing with the 3' untranslated region. We previously reported amplification and
      overexpression of the miR-17-92 miRNA cluster at 13q31.3 in lung cancers, as well
      as growth inhibition by treatment with antisense oligonucleotides against miR-17
      5p and miR-20a, constituents of miR-17-92, specifically in miR-17-92
      overexpressing lung cancer cell lines. Although these findings clearly suggested
      important roles of miR-17-92 overexpression in lung cancers, only a few targets
      for the miR-17-92 cluster have been identified thus far. In this study, we
      identified hypoxia-inducible factor (HIF)-1 alpha as a novel direct target for
      miR-17-92 through global expression profiling by mass spectrometric analysis
      using an isobaric tagging reagent, iTRAQ, combined with bioinformatic target
      prediction. This is the first report to describe negative regulation of HIF-1
      alpha by miRNA, which seemed to occur without disrupting the induction of HIF-1
      alpha for cellular adaptation to hypoxia. In addition, overexpression of c-myc
      led to down-regulation of HIF-1 alpha and induction of miR-17-92, the latter of
      which was previously reported to be a transcriptional activation activity,
      suggesting that the induction of miR-17-92 may play a role at least in part in c
      myc-mediated repression of HIF-1 alpha. Together with previous reports on the
      functional negative regulation of c-myc by HIF-1 alpha, our findings suggest the
      possible existence of an intricate and finely tuned circuit involving c-myc, miR
      17-92, and HIF-1 alpha that may play a role in cancer cell proliferation under
      normoxia in a cellular context-dependent manner.

PMID- 18632606
TI  - CTCFL/BORIS is a methylation-independent DNA-binding protein that preferentially
      binds to the paternal H19 differentially methylated region.
AB  - The CTCF paralog BORIS (brother of the regulator of imprinted sites) is an
      insulator DNA-binding protein thought to play a role in chromatin organization
      and gene expression. Under normal physiologic conditions, BORIS is predominantly
      expressed during embryonic male germ cell development; however, it is also
      expressed in tumors and tumor cell lines and, as such, has been classified as a
      cancer-germline or cancer-testis gene. It has been suggested that BORIS may be a
      pro-proliferative factor, whereas CTCF favors antiproliferation. BORIS and CTCF
      share similar zinc finger DNA-binding domains and seem to bind to identical
      target sequences. Thus, one critical question is the mechanism governing the DNA
      binding specificity of these two proteins when both are present in tumor cells.
      Chromatin immunoprecipitation (ChIP) in HCT116 cells and their hypermethylated
      variant showed that BORIS binds to methylated DNA sequences, whereas CTCF binds
      to unmethylated DNA. Electromobility shift assays, using both whole-cell extracts
      and in vitro translated CTCF and BORIS protein, and methylation-specific ChIP PCR
      showed that BORIS is a methylation-independent DNA-binding protein. Finally,
      experiments in murine hybrid cells containing either the maternal or paternal
      human chromosome 11 showed that BORIS preferentially binds to the methylated
      paternal H19 differentially methylated region, suggesting a mechanism in which
      the affinity of CTCF for the unmethylated maternal allele directs the DNA binding
      of BORIS toward the paternal allele.

PMID- 18632607
TI  - Targeted deletion of Rad9 in mouse skin keratinocytes enhances genotoxin-induced
      tumor development.
AB  - The Rad9 gene is evolutionarily conserved from yeast to humans and plays crucial
      roles in genomic maintenance, DNA repair, and cell cycle checkpoint controls.
      However, the function of this gene with respect to tumorigenesis is not well
      understood. A Rad9-null mutation in mice causes embryonic lethality. In this
      study, we created mice in which mouse Rad9, Mrad9, was deleted only in
      keratinocytes to permit examination of the potential function of the gene in
      tumor development. Mice with Mrad9(+/-) or Mrad9(-/-) keratinocytes showed no
      overt, spontaneous morphologic defects and seemed similar to wild-type controls.
      Painting the carcinogen 7,12-dimethylbenzanthracene (DMBA) onto the skin of the
      animals caused earlier onset and more frequent formation of tumors and senile
      skin plaques in Mrad9(-/-) mice, compared with Mrad9(+/-) and Mrad9(+/+)
      littermates. DNA damage response genes p21, p53, and Mrad9B were expressed at
      higher levels in Mrad9(-/-) relative to Mrad9(+/+) skin. Keratinocytes isolated
      from Mrad9(-/-) skin had more spontaneous and DMBA-induced DNA double strand
      breaks than Mrad9(+/+) keratinocytes, and the levels were reduced by incubation
      with the antioxidant epigallocatechin gallate. These data suggest that Mrad9
      plays an important role in maintaining genomic stability and preventing tumor
      development in keratinocytes.

PMID- 18632608
TI  - GSTP1 promoter haplotypes affect DNA methylation levels and promoter activity in
      breast carcinomas.
AB  - The CpG island spanning the transcription start of the glutathione S-transferase
      P1 becomes methylated in a variety of human cancers including breast cancer. To
      study the effect of sequence variation on hypermethylation of the GSTP1 promoter,
      we analyzed the genetic and epigenetic variability in 90 tumors from patients
      with locally advanced breast cancer. High-resolution quantitative analysis
      revealed large variability in the DNA methylation levels. Lack of methylation was
      more often observed in the basal and normal-like estrogen receptor (ER)-negative
      tumors, and methylated GSTP1 was associated with better overall survival (P =
      0.00063). Studies of the genetic variation identified 14 different haplotypes.
      The distribution of methylation levels of tumors homozygous for the most frequent
      haplotype was significantly different from other haplotype combinations (P =
      0.011), the difference being more pronounced in ER-positive (P = 0.005) and
      progesterone receptor-positive (P = 0.008) tumors. Regression modeling identified
      the ER status and haplotype as the main determinants of DNA methylation
      variability. We identified a putative c-Myb response element (MRE) that was
      present in one of two minimal promoter haplotypes. In vitro analysis showed that
      c-Myb binds to the MRE, but binding was weakened by the two polymorphisms.
      Transient cotransfections in luminal-type and basal-like breast cancer cell lines
      confirmed cell-specific differential binding of c-Myb to the polymorphic sites,
      leading to a change in the expression from the GSTP1 promoter in vivo. GSTP1
      expression was moderately but significantly (P = 0.01) reduced after siRNA
      mediated knockdown of c-Myb. Our results indicate that haplotype structure of a
      promoter is important for the extent of DNA methylation.

PMID- 18632609
TI  - Tripartite motif protein 32 facilitates cell growth and migration via degradation
      of Abl-interactor 2.
AB  - Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly
      expressed in human head and neck squamous cell carcinoma, but the involvement of
      TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found
      by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2),
      which is known as a tumor suppressor and a cell migration inhibitor, and we
      showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32
      promoted degradation of Abi2, resulting in enhancement of cell growth,
      transforming activity, and cell motility, whereas a dominant-negative mutant of
      TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we
      found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum
      (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene
      that promotes tumor growth, metastasis, and resistance to anticancer drugs.

PMID- 18632610
TI  - A role for the cyclin box in the ubiquitin-mediated degradation of cyclin G1.
AB  - Cyclin G1 was identified as a transcriptional target of p53 that encodes a
      protein with strong homology to the cyclin family of cell cycle regulators. We
      show that either ectopically expressed or endogenous cyclin G1 protein is very
      unstable, undergoes modification with ubiquitin, and is likely degraded by the
      proteasome. Ectopic cyclin G1 protein stability is increased by cyclin box
      mutation or by association with inactive cyclin-dependent kinase (CDK) subunits,
      suggesting that a function of cyclin G1 as a CDK regulator may be required for
      its rapid turnover. Furthermore, cyclin G1 and the cyclin box mutant interact
      with and are ubiquitinated by MDM2, another transcriptional target of p53 that
      acts as a negative regulator of p53 stability. These data suggest that the cyclin
      box has a role in the proteasome-mediated degradation of cyclin G1 and thus
      suggest a putative role for a CDK in cyclin G1 metabolism and function.

PMID- 18632611
TI  - PIK3IP1, a negative regulator of PI3K, suppresses the development of
      hepatocellular carcinoma.
AB  - Phosphatidylinositol-3-kinase (PI3K) is a well-known regulator of cell division,
      motility, and survival in most cell types. Recently, we characterized a novel
      protein that we call PI3K Interacting Protein 1 (PIK3IP1), which binds to the
      p110 catalytic subunit of PI3K and reduces its activity in vitro. Little is known
      about the role of PIK3IP1 in normal and neoplastic growth in vivo. Proper liver
      function and development depend on intact PI3K signal transduction; when
      dysregulated, the PI3K pathway is linked to the development of liver cancer. To
      begin to dissect the contribution of PIK3IP1 to hepatic PI3K signaling in vivo
      and to liver tumorigenesis in particular, we formulated the following hypothesis:
      because PIK3IP1 down-regulates PI3K signaling and uncontrolled PI3K signaling is
      associated with liver cancer, then PIK3IP1-mediated down-regulation of the PI3K
      pathway should inhibit hepatocellular carcinoma (HCC) development. To test this
      idea, we generated transgenic mice overexpressing PIK3IP1 in hepatocytes in a
      mouse strain prone to develop HCC. Isolated PIK3IP1 transgenic mouse hepatocytes
      showed blunted PI3K signaling, DNA synthetic activity, motility, and survival
      compared with controls. In vivo, spontaneous liver tumorigenesis was
      significantly dampened in the transgenic animals. This was accompanied by
      decreased hepatic PI3K activity and reduced hepatocyte proliferation in the
      transgenics compared with controls. We also observed that human HCC expressed
      less PIK3IP1 protein than adjacent matched liver tissue. Our data show that
      PIK3IP1 is an important regulator of PI3K in vivo, and its dysregulation can
      contribute to liver carcinogenesis.

PMID- 18632612
TI  - Genomic alterations indicate tumor origin and varied metastatic potential of
      disseminated cells from prostate cancer patients.
AB  - Disseminated epithelial cells can be isolated from the bone marrow of a far
      greater fraction of prostate-cancer patients than the fraction of patients who
      progress to metastatic disease. To provide a better understanding of these cells,
      we have characterized their genomic alterations. We first present an array
      comparative genomic hybridization method capable of detecting genomic changes in
      the small number of disseminated cells (10-20) that can typically be obtained
      from bone marrow aspirates of prostate-cancer patients. We show multiple regions
      of copy-number change, including alterations common in prostate cancer, such as
      8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the
      disseminated cell pools from 11 metastatic patients. We found fewer and less
      striking genomic alterations in the 48 pools of disseminated cells from patients
      with organ-confined disease. However, we identify changes shared by these samples
      with their corresponding primary tumors and prostate-cancer alterations reported
      in the literature, evidence that these cells, like those in advanced disease, are
      disseminated tumor cells (DTC). We also show that DTCs from patients with
      advanced and localized disease share several abnormalities, including losses
      containing cell-adhesion genes and alterations reported to associate with
      progressive disease. These shared alterations might confer the capability to
      disseminate or establish secondary disease. Overall, the spectrum of genomic
      deviations is evidence for metastatic capacity in advanced-disease DTCs and for
      variation in that capacity in DTCs from localized disease. Our analysis lays the
      foundation for elucidation of the relationship between DTC genomic alterations
      and progressive prostate cancer.

PMID- 18632613
TI  - Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1
      and contributes to apoptosis in colorectal cancer cells.
AB  - There are few reports describing the role of p53-dependent gene repression in
      apoptotic cell death. To identify such apoptosis-associated p53 target genes, we
      used the pro-oxidant plant-derived drug thymoquinone and compared p53+/+ and p53
      /- colon cancer cells HCT116. The p53 wild-type (wt) status correlated with more
      pronounced DNA damage and higher apoptosis after thymoquinone treatment. A
      significant up-regulation of the survival gene CHEK1 was observed in p53-/- cells
      in response to thymoquinone due to the lack of transcriptional repression of p53.
      In p53-/- cells, transfection with p53-wt vector and CHEK1 small interfering RNA
      treatment decreased CHEK1 mRNA and protein levels and restored apoptosis to the
      levels of the p53+/+ cells. p53-/- cells transplanted to nude mice treated with
      thymoquinone up-regulated CHEK1 expression and did not undergo apoptosis unlike
      p53+/+ cells. Immunofluorescence analysis revealed that the apoptosis resistance
      in p53-/- cells after thymoquinone treatment might be conveyed by shuttling of
      CHEK1 into the nucleus. We confirmed the in vivo existence of this CHEK1/p53 link
      in human colorectal cancer, showing that tumors lacking p53 had higher levels of
      CHEK1, which was accompanied by poorer apoptosis. CHEK1 overexpression was
      correlated with advanced tumor stages (P = 0.03), proximal tumor localization (P
      = 0.02), and worse prognosis (1.9-fold risk, univariate Cox regression; Kaplan
      Meier, P = 0.04). We suggest that the inhibition of the stress response sensor
      CHEK1 might contribute to the antineoplastic activity of specific DNA-damaging
      drugs.

PMID- 18632614
TI  - Conditional loss of uterine Pten unfailingly and rapidly induces endometrial
      cancer in mice.
AB  - Etiology of endometrial cancer (EMC) is not fully understood. Animal models with
      rapidly and spontaneously developing EMC will help explore mechanisms of cancer
      initiation and progression. Pten(+/-) mice are currently being used as a model to
      study EMC. These females develop atypical endometrial hyperplasia of which
      approximately 20% progresses to EMC. In addition, tumors develop in other organs,
      complicating the use of this model to specifically study EMC. Here, we show that
      conditional deletion of endometrial Pten results in EMC in all female mice as
      early as age 1 month with myometrial invasion occurring by 3 months. In contrast,
      conditional deletion of endometrial p53 had no phenotype within this time frame.
      Whereas mice with endometrial Pten deletion had a life span of approximately 5
      months, mice with combined deletion of endometrial Pten and p53 had a shorter
      life span with an exacerbated disease state. Such rapid development of EMC from
      homozygous loss of endometrial Pten suggests that this organ is very sensitive to
      this tumor suppressor gene for tumor development. All lesions at early stages
      exhibited elevated Cox-2 and phospho-Akt levels, hallmarks of solid tumors. More
      interestingly, levels of two microRNAs miR-199a(*) and miR-101a that
      posttranscriptionally inhibit Cox-2 expression were down-regulated in tumors in
      parallel with Cox-2 up-regulation. This mouse model in which the loxP-Cre system
      has been used to delete endometrial Pten and/or p53 allows us to study in detail
      the initiation and progression of EMC. These mouse models have the added
      advantage because they mimic several features of human EMC.

PMID- 18632615
TI  - Cyclin D1b is aberrantly regulated in response to therapeutic challenge and
      promotes resistance to estrogen antagonists.
AB  - Cyclin D1 is a key mediator of cell cycle progression that is aberrantly
      regulated in multiple cancers, especially in breast cancers. A number of studies
      have indicated that a polymorphism in a splice donor site in the cyclin D1 gene
      is associated with alternative splicing and the production of the alternative
      cyclin D1b transcript. Furthermore, this polymorphism is selectively associated
      with disease outcomes. However, relatively little is known regarding the protein
      product of the alternatively spliced message, cyclin D1b. Using antibodies
      specific for cyclin D1b, it was found that this protein is readily detectable in
      a number of cancer cell lines and primary breast cancers. Whereas cyclin D1b
      interacts with cyclin-dependent kinase 4 (CDK4), it is relatively inefficient at
      mediating RB phosphorylation and cell cycle progression in model systems due to
      the lack of exon 5 of cyclin D1-encoded sequences. However, cyclin D1b protein
      levels are not significantly attenuated by DNA damage or antiestrogen treatment,
      indicating that the protein may have significant effect on the response to such
      therapeutic modalities. Whereas enforced expression of cyclin D1b was not
      sufficient to abrogate DNA damage checkpoint responses, it did efficiently
      overcome cell cycle arrest mediated by antiestrogen therapeutics. This action of
      cyclin D1b was not associated with effects on estrogen receptor activity, but was
      rather dependent on functional association with CDK4. Combined, these studies
      indicate that the cyclin D1b protein is aberrantly regulated and could contribute
      to therapeutic failure in the context of ER-positive breast cancer.

PMID- 18632616
TI  - A special linker between macrophage and hematopoietic malignant cells: membrane
      form of macrophage colony-stimulating factor.
AB  - The membrane form of macrophage colony-stimulating factor (mM-CSF) is an
      alternative splicing variant of this cytokine. Although its high expression was
      detected in hematopoietic malignancies, its physiologic and pathologic roles in
      hematopoietic system have not been established. In this report, stable
      transfectant clones expressing mM-CSF (Namalwa-M and Ramos-M) were obtained,
      which showed reduced proliferation potential in vitro. Moreover, the in vivo
      study showed that Namalwa-M and Ramos-M exhibited enhanced oncogenicity in tumor
      size in nude mice model, which could be inhibited by M-CSF monoclonal antibody. A
      remarkable increase in infiltrating macrophage and the vessel densities was found
      in tumor tissues formed by lymphoma cell lines that stably expressed mM-CSF,
      which suggested the involvement of macrophages in this process. The in vitro
      results using coculture system showed that macrophages could promote Namalwa-M
      and Ramos-M proliferation and activate extracellular signal-regulated
      kinase/mitogen-activated protein kinase signal pathway. In addition, the
      expression of murine origin vascular endothelial growth factor, basic fibroblast
      growth factor, and hepatocyte growth factor was elevated in Namalwa-M formed
      tumor tissues. These results suggested that mM-CSF should be a positive regulator
      in the development of hematopoietic malignancies by abnormally activating
      infiltrating macrophages, which in turn promote the malignant development. Thus,
      mM-CSF may be a critical linker between macrophages and malignant cells in the
      development of hematopoietic malignancies.

PMID- 18632617
TI  - SerpinB2 protection of retinoblastoma protein from calpain enhances tumor cell
      survival.
AB  - The tumor suppressor retinoblastoma protein (Rb) plays a pivotal role in the
      regulation of cell proliferation and sensitivity to apoptosis through binding to
      E2F transcription factors. Loss of Rb in response to genotoxic stress or
      inflammatory cytokines can enhance cell death, in part, by eliminating Rb
      mediated repression of proapoptotic gene transcription. Here we show that calpain
      cleavage of Rb facilitates Rb loss by proteasome degradation and that this may
      occur during tumor necrosis factor alpha-induced apoptosis. The cytoprotective,
      Rb-binding protein SerpinB2 (plasminogen activator inhibitor type 2) protects Rb
      from calpain cleavage, increasing Rb levels and enhancing cell survival.
      Chromatin immunoprecipitation assays show that the increased Rb levels
      selectively enhance Rb repression of proapoptotic gene transcription. This
      cytoprotective role of SerpinB2 is illustrated by reduced susceptibility of
      SerpinB2-deficient mice to multistage skin carcinogenesis, where Rb-dependent
      cell proliferation competes with apoptosis during initiation of papilloma
      development. These data identify SerpinB2 as a cell survival factor that
      modulates Rb repression of proapoptotic signal transduction and define a new
      posttranslational mechanism for selective regulation of the intracellular levels
      of Rb.

PMID- 18632618
TI  - The side population of ovarian cancer cells is a primary target of IFN-alpha
      antitumor effects.
AB  - The side population (SP), recently identified in several normal tissues and in a
      variety of tumors based on its ability to extrude some fluorescent dyes, may
      comprise cells endowed with stem cell features. In this study, we investigated
      the presence of SP in epithelial ovarian cancer and found it in 9 of 27 primary
      tumor samples analyzed, as well as in 4 of 6 cultures from xenotransplants. SP
      cells from one xenograft bearing a large SP fraction were characterized in
      detail. SP cells had higher proliferation rates, were much less apoptotic
      compared with non-SP cells, and generated tumors more rapidly than non-SP cells.
      We also investigated the effects of IFN-alpha, a cytokine that has widely been
      used to treat solid tumors, on epithelial ovarian cancer cells and observed that
      IFN-alpha exerted marked antiproliferative and proapoptotic effects on primary
      cultures containing high numbers of SP cells. In vitro, IFN-alpha treatment
      invariably caused a dramatic reduction in SP size in tumor cell lines of
      different origins; moreover, IFN-alpha treatment of purified SP cells was
      associated with a distinctive change in their transcriptional profile. Gene
      therapy with human IFN-alpha resulted in regression of established tumors bearing
      a large SP fraction, which was not observed when tumors bearing low SP levels
      were treated. These findings could have relevant clinical implications because
      they imply that tumors bearing large SP numbers, albeit rare, could be sensitive
      to IFN-alpha treatment.

PMID- 18632619
TI  - Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor
      with distinct roles from Mdm2 in receptor ubiquitination and endocytosis.
AB  - The insulin-like growth factor receptor (IGF-IR) plays several pivotal roles in
      cancer. Although most studies on the function of the IGF-IR have been attributed
      to kinase-dependent signaling, recent findings by our group and others have
      implicated biological roles mediated by ubiquitination of the receptor. As
      previously reported, the E3 ligases Mdm2 and Nedd4 mediate IGF-IR ubiquitination.
      Here we show that c-Cbl is a novel E3 ligase for IGF-IR. On ligand stimulation,
      both Mdm2 and c-Cbl associate with IGF-IR and mediate receptor
      polyubiquitination. Whereas Mdm2 catalyzed lysine 63 (K63) chain ubiquitination,
      c-Cbl modified IGF-IR through K48 chains. Mdm2-mediated ubiquitination occurred
      when cells were stimulated with a low concentration (5 ng/mL) of IGF-I, whereas c
      Cbl required high concentrations (50-100 ng/mL). Mdm2-ubiquitinated IGF-IR was
      internalized through the clathrin endocytic pathway whereas c-Cbl-ubiquitinated
      receptors were endocytosed via the caveolin route. Taken together, our results
      show that c-Cbl constitutes a new ligase responsible for the ubiquitination of
      IGF-IR and that it complements the action of Mdm2 on ubiquitin lysine residue
      specificity, responsiveness to IGF-I, and type of endocytic pathway used. The
      actions and interactions of Mdm2 and c-Cbl in the ubiquitination and endocytosis
      of IGF-IR may have implications in cancer. In addition, identification and
      functional characterization of new E3 ligases are important in itself because
      therapeutic targeting of substrate-specific E3 ligases is likely to represent a
      critical strategy in future cancer treatment.

PMID- 18632620
TI  - Vimentin filaments support extension of tubulin-based microtentacles in detached
      breast tumor cells.
AB  - Solid tumor metastasis often involves detachment of epithelial carcinoma cells
      into the vasculature or lymphatics. However, most studies of cytoskeletal
      rearrangement in solid tumors focus on attached cells. In this study, we report
      for the first time that human breast tumor cells produce unique tubulin-based
      protrusions when detached from extracellular matrix. Tumor cell lines of high
      metastatic potential show significantly increased extension and frequency of
      microtubule protrusions, which we have termed tubulin microtentacles. Our
      previous studies in nontumorigenic mammary epithelial cells showed that such
      detachment-induced microtentacles are enriched in detyrosinated alpha-tubulin.
      However, amounts of detyrosinated tubulin were similar in breast tumor cell lines
      despite varying microtentacle levels. Because detyrosinated alpha-tubulin
      associates strongly with intermediate filament proteins, we examined the
      contribution of cytokeratin and vimentin filaments to tumor cell microtentacles.
      Increased microtentacle frequency and extension correlated strongly with loss of
      cytokeratin expression and up-regulation of vimentin, as is often observed during
      tumor progression. Moreover, vimentin filaments coaligned with microtentacles,
      whereas cytokeratin did not. Disruption of vimentin with PP1/PP2A-specific
      inhibitors significantly reduced microtentacles and inhibited cell reattachment
      to extracellular matrix. Furthermore, expression of a dominant-negative vimentin
      mutant disrupted endogenous vimentin filaments and significantly reduced
      microtentacles, providing specific genetic evidence that vimentin supports
      microtentacles. Our results define a novel model in which coordination of
      vimentin and detyrosinated microtubules provides structural support for the
      extensive microtentacles observed in detached tumor cells and a possible
      mechanism to promote successful metastatic spread.

PMID- 18632621
TI  - Overexpression of vascular endothelial growth factor and the development of post
      transplantation cancer.
AB  - Cancer is an increasing and major problem after solid organ transplantation. In
      part, the increased cancer risk is associated with the use of immunosuppressive
      agents, especially calcineurin inhibitors. We propose that the effect of
      calcineurin inhibitors on the expression of vascular endothelial growth factor
      (VEGF) leads to an angiogenic milieu that favors tumor growth. Here, we used 786
      0 human renal cancer cells to investigate the effect of cyclosporine (CsA) on
      VEGF expression. Using a full-length VEGF promoter-luciferase construct, we found
      that CsA markedly induced VEGF transcriptional activation through the protein
      kinase C (PKC) signaling pathway, specifically involving PKC zeta and PKC delta
      isoforms. Moreover, CsA promoted the association of PKC zeta and PKC delta with
      the transcription factor Sp1 as observed by immunoprecipitation assays. Using
      promoter deletion constructs, we found that CsA-mediated VEGF transcription was
      primarily Sp1 dependent. Furthermore, CsA-induced and PKC-Sp1-mediated VEGF
      transcriptional activation was partially inhibited by von Hippel-Lindau protein.
      CsA also promoted the progression of human renal tumors in vivo, wherein VEGF is
      overexpressed. Finally, to evaluate the in vivo significance of CsA-induced VEGF
      overexpression in terms of post-transplantation tumor development, we injected
      CT26 murine carcinoma cells (known to form angiogenic tumors) into mice with
      fully MHC mismatched cardiac transplants. We observed that therapeutic doses of
      CsA increased tumor size and VEGF mRNA expression and also enhanced tumor
      angiogenesis. However, coadministration of a blocking anti-VEGF antibody
      inhibited this CsA-mediated tumor growth. Collectively, these findings define PKC
      mediated VEGF transcriptional activation as a key component in the progression of
      CsA-induced post-transplantation cancer.

PMID- 18632622
TI  - An in vitro multistep carcinogenesis model for human cervical cancer.
AB  - Human papillomaviruses (HPV) are believed to be the primary causal agents for
      development of cervical cancer, and deregulated expression of two viral oncogenes
      E6 and E7 in basal cells, mostly by integration, is considered to be a critical
      event for disease progression. However, lines of evidence suggest that, besides
      expression of E6 and E7 genes, additional host genetic alterations are required
      for cancer development. To directly test this hypothesis, we first transduced
      HPV16 E6 and E7 with or without hTERT into several lines of normal human cervical
      keratinocytes (HCK) from independent donors and then searched for additional
      alterations required for carcinogenesis. Oncogenic Hras(G12V) (Hras) provided
      marked tumor forming ability in nude mice and ErbB2 or c-Myc (Myc) endowed weaker
      but significant tumor forming ability. Combined transduction of Myc and Hras to
      HCKs expressing E6 and E7 resulted in the creation of highly potent tumor
      initiating cells. These results show that only one or two genetic changes
      occurring after deregulated expression of high-risk HPV oncogenes might be
      sufficient for development of cervical cancer.

PMID- 18632623
TI  - Temozolomide preferentially depletes cancer stem cells in glioblastoma.
AB  - The prognosis of patients suffering from glioblastoma (GBM) is dismal despite
      multimodal therapy. Although chemotherapy with temozolomide may contain tumor
      growth for some months, invariable tumor recurrence suggests that cancer stem
      cells (CSC) maintaining these tumors persist. We have therefore investigated the
      effect of temozolomide on CD133(+) and CD133(-) GBM CSC lines. Although
      differentiated tumor cells constituting the bulk of all tumor cells were
      resistant to the cytotoxic effects of the substance, temozolomide induced a dose-
      and time-dependent decline of the stem cell subpopulation. Incubation with
      sublethal concentrations of temozolomide for 2 days completely depleted
      clonogenic tumor cells in vitro and substantially reduced tumorigenicity in vivo.
      In O(6)-methylguanine-DNA-methyltransferase (MGMT)-expressing CSC lines, this
      effect occurred at 10-fold higher doses compared with MGMT-negative CSC lines.
      Thus, temozolomide concentrations that are reached in patients were only
      sufficient to completely eliminate CSC in vitro from MGMT-negative but not from
      MGMT-positive tumors. Accordingly, our data strongly suggest that optimized
      temozolomide-based chemotherapeutic protocols might substantially improve the
      elimination of GBM stem cells and consequently prolong the survival of patients.

PMID- 18632624
TI  - Jagged-1 and Notch3 juxtacrine loop regulates ovarian tumor growth and adhesion.
AB  - Notch3 gene amplification and pathway activation have been reported in ovarian
      serous carcinoma. However, the primary Notch3 ligand that initiates signal
      transduction in ovarian cancer remains unclear. In this report, we identify
      Jagged-1 as the highest expressed Notch ligand in ovarian tumor cells as well as
      in peritoneal mesothelial cells that are in direct contact with disseminated
      ovarian cancer cells. Cell-cell adhesion and cellular proliferation were reduced
      in Notch3-expressing ovarian cancer cells that were cocultured with Jagged-1
      knockdown mesothelial and tumor feeder cells. Interaction of Notch3-expressing
      ovarian cancer cells with Jagged-1-expressing feeder cells activated the promoter
      activity of candidate Notch3 target genes, and this activity was attenuated by
      Notch3 siRNA. Constitutive expression of the Notch3 intracellular domain
      significantly suppressed the Jagged-1 shRNA-mediated growth inhibitory effect. In
      Notch3-expressing ovarian cancer cells, Jagged-1-stimulating peptides enhanced
      cellular proliferation, which was suppressed by gamma-secretase inhibitor and
      Notch3 siRNA. Taken together, our results show that Jagged-1 is the primary
      Notch3 ligand in ovarian carcinoma and Jagged-1/Notch3 interaction constitutes a
      juxtacrine loop promoting proliferation and dissemination of ovarian cancer cells
      within the intraperitoneal cavity.

PMID- 18632625
TI  - PAX8 regulates telomerase reverse transcriptase and telomerase RNA component in
      glioma.
AB  - Paired box (PAX) developmental genes are frequently expressed in cancers and
      confer survival advantages on cancer cells. We have previously found that PAX
      genes are deregulated in glioma. We have now investigated the expression of PAX
      genes in glioma and their role in telomere maintenance. The mRNA level of PAX8
      showed a positive correlation with telomerase activity in glioma biopsies (r(2) =
      0.75, P < 0.001) and in established glioma cell lines (r(2) = 0.97, P = 0.0025).
      We found that PAX8 is able to coordinately transactivate the promoter for both
      the telomerase catalytic subunit (hTERT) and the telomerase RNA component (hTR)
      genes. By electrophoretic mobility shift assay, quantitative PCR, and a
      telomerase activity assay, we show that PAX8 binds directly to the hTERT and hTR
      promoters, up-regulating hTERT and hTR mRNA, as well as telomerase activity.
      Additionally, PAX8 small interfering RNA down-regulated hTERT and hTR.
      Collectively, these results show that PAX8 may have a role in telomerase
      regulation.

PMID- 18632626
TI  - Merlin is a potent inhibitor of glioma growth.
AB  - Neurofibromatosis 2 (NF2) is an inherited cancer syndrome in which affected
      individuals develop nervous system tumors, including schwannomas, meningiomas,
      and ependymomas. The NF2 protein merlin (or schwannomin) is a member of the Band
      4.1 superfamily of proteins, which serve as linkers between transmembrane
      proteins and the actin cytoskeleton. In addition to mutational inactivation of
      the NF2 gene in NF2-associated tumors, mutations and loss of merlin expression
      have also been reported in other types of cancers. In the present study, we show
      that merlin expression is dramatically reduced in human malignant gliomas and
      that reexpression of functional merlin dramatically inhibits both subcutaneous
      and intracranial growth of human glioma cells in mice. We further show that
      merlin reexpression inhibits glioma cell proliferation and promotes apoptosis in
      vivo. Using microarray analysis, we identify altered expression of specific
      molecules that play key roles in cell proliferation, survival, and motility.
      These merlin-induced changes of gene expression were confirmed by real-time
      quantitative PCR, Western blotting, and functional assays. These results indicate
      that reexpression of merlin correlates with activation of mammalian sterile 20
      like 1/2-large tumor suppressor 2 signaling pathway and inhibition of canonical
      and noncanonical Wnt signals. Collectively, our results show that merlin is a
      potent inhibitor of high-grade human glioma.

PMID- 18632627
TI  - Identification of a novel subgroup of melanomas with KIT/cyclin-dependent kinase
      4 overexpression.
AB  - Although many melanomas harbor either activating mutations in BRAF or NRAS, there
      remains a substantial, yet little known, group of tumors without either mutation.
      Here, we used a genomic strategy to define a novel group of melanoma cell lines
      with co-overexpression of cyclin-dependent kinase 4 (CDK4) and KIT. Although this
      subgroup lacked any known KIT mutations, they had high phospho-KIT receptor
      expression, indicating receptor activity. Quantitative PCR confirmed the
      existence of a similar KIT/CDK4 subgroup in human melanoma samples. Pharmacologic
      studies showed the KIT/CDK4-overexpressing subgroup to be resistant to BRAF
      inhibitors but sensitive to imatinib in both in vitro and in vivo melanoma
      models. Mechanistically, imatinib treatment led to increased apoptosis and G(1)
      phase cell cycle arrest associated with the inhibition of phospho-ERK and
      increased expression of p27(KIP). Other melanoma cell lines, which retained some
      KIT expression but lacked phospho-KIT, were not sensitive to imatinib, suggesting
      that KIT expression alone is not predictive of response. We suggest that co
      overexpression of KIT/CDK4 is a potential mechanism of oncogenic transformation
      in some BRAF/NRAS wild-type melanomas. This group of melanomas may be a
      subpopulation for which imatinib or other KIT inhibitors may constitute optimal
      therapy.

PMID- 18632628
TI  - Defining a chromatin pattern that characterizes DNA-hypermethylated genes in
      colon cancer cells.
AB  - Epigenetic gene regulation is a key determinant of heritable gene expression
      patterns and is critical for normal cellular function. Dysregulation of
      epigenetic transcriptional control is a fundamental feature of cancer,
      particularly manifesting as increased promoter DNA methylation with associated
      aberrant gene silencing, which plays a significant role in tumor progression. We
      now globally map key chromatin parameters for genes with promoter CpG island DNA
      hypermethylation in colon cancer cells by combining microarray gene expression
      analyses with chromatin immunoprecipitation-on-chip technology. We first show
      that the silent state of such genes universally correlates with a broad
      distribution of a low but distinct level of the PcG-mediated histone
      modification, methylation of lysine 27 of histone 3 (H3K27me), and a very low
      level of the active mark H3K4me2. This chromatin pattern, and particularly
      H3K4me2 levels, crisply separates DNA-hypermethylated genes from those where
      histone deacetylation is responsible for transcriptional silencing. Moreover, the
      chromatin pattern can markedly enhance identification of truly silent and DNA
      hypermethylated genes. We additionally find that when DNA-hypermethylated genes
      are demethylated and reexpressed, they adopt a bivalent chromatin pattern, which
      is associated with the poised gene expression state of a large group of embryonic
      stem cell genes and is characterized by an increase in levels of both the
      H3K27me3 and H3K4me2 marks. Our data have great relevance for the increasing
      interest in reexpression of DNA-hypermethylated genes for the treatment of
      cancer.

PMID- 18632629
TI  - Pten deficiency in melanocytes results in resistance to hair graying and
      susceptibility to carcinogen-induced melanomagenesis.
AB  - Phosphate and tensin homologue deleted on chromosome 10 (PTEN) is a tumor
      suppressor gene inactivated in numerous sporadic cancers, including melanomas. To
      analyze Pten functions in melanocytes, we used the Cre-loxP system to delete Pten
      specifically in murine pigment-producing cells and generated
      DctCrePten(flox/flox) mice. Half of DctCrePten(flox/flox) mice died shortly after
      birth with enlargements of the cerebral cortex and hippocampus. Melanocytes were
      increased in the dermis of perinatal DctCrePten(flox/flox) mice. When the mutants
      were subjected to repeated depilations, melanocyte stem cells in the bulge of the
      hair follicle resisted exhaustion and the mice were protected against hair
      graying. Although spontaneous melanomas did not form in DctCrePten(flox/flox)
      mice, large nevi and melanomas developed after carcinogen exposure.
      DctCrePten(flox/flox) melanocytes were increased in size and exhibited heightened
      activation of Akt and extracellular signal-regulated kinases, increased
      expression of Bcl-2, and decreased expression of p27(Kip1). Our results show that
      Pten is important for the maintenance of melanocyte stem cells and the
      suppression of melanomagenesis.

PMID- 18632630
TI  - Coupling of mutated Met variants to DNA repair via Abl and Rad51.
AB  - Abnormal activation of DNA repair pathways by deregulated signaling of receptor
      tyrosine kinase systems is a compelling likelihood with significant implications
      in both cancer biology and treatment. Here, we show that due to a potential
      substrate switch, mutated variants of the receptor for hepatocyte growth factor
      Met, but not the wild-type form of the receptor, directly couple to the Abl
      tyrosine kinase and the Rad51 recombinase, two key signaling elements of
      homologous recombination-based DNA repair. Treatment of cells that express the
      mutated receptor variants with the Met inhibitor SU11274 leads, in a mutant
      dependent manner, to a reduction of tyrosine phosphorylated levels of Abl and
      Rad51, impairs radiation-induced nuclear translocation of Rad51, and acts as a
      radiosensitizer together with the p53 inhibitor pifithrin-alpha by increasing
      cellular double-strand DNA break levels following exposure to ionizing radiation.
      Finally, we propose that in order to overcome a mutation-dependent resistance to
      SU11274, this aberrant molecular axis may alternatively be targeted with the Abl
      inhibitor, nilotinib.

PMID- 18632631
TI  - Low-dose radiation enhances survivin-mediated virotherapy against malignant
      glioma stem cells.
AB  - To improve the efficacy and selectivity of virotherapy for malignant glioma, we
      designed a strategy to amplify adenoviral replication in conjunction with
      radiotherapy using a radioinducible promoter. First, we compared the radiation
      inducible activity of FLT-1, vascular endothelial growth factor, DR5, Cox2, and
      survivin. We then examined the capacity of the optimal promoter to modulate
      transgene expression followed by E1A activity in vitro and in vivo in a glioma
      stem cell model. In the presence of radiation, survivin mRNA activity increased
      10-fold. Luciferase transgene expression was dose dependent and optimal at 2 Gy.
      A novel oncolytic adenovirus, CRAd-Survivin-pk7, showed significant toxicity and
      replication against a panel of passaged and primary CD133(+) glioma stem cells.
      On delivery of radiation, the toxicity associated with CRAd-Survivin-pk7
      increased by 20% to 50% (P < 0.05). At the same time, the level of E1A activity
      increased 3- to 10-fold. In vivo, treatment of U373MG CD133(+) stem cells with
      CRAd-Survivin-pk7 and radiation significantly inhibited tumor growth (P < 0.05).
      At the same time, the level of E1A activity was 100-fold increased versus CRAd
      Survivin-pk7 alone. Selected genes linked to radioinducible promoters whose
      expression can be regulated by ionizing radiation may improve the therapeutic
      ratio of virotherapy. In this study, we have identified a new radioinducible
      promoter, survivin, which greatly enhances the activity of an oncolytic
      adenovirus in the presence of low-dose radiotherapy.

PMID- 18632632
TI  - Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic
      protein-dependent and independent mechanisms.
AB  - Prostate cancer (PCa) is frequently accompanied by osteosclerotic (i.e.,
      excessive bone production) bone metastases. Although bone morphogenetic proteins
      (BMP) and Wnts are mediators of PCa-induced osteoblastic activity, the relation
      between them in PCa bone metastases is unknown. The goal of this study was to
      define this relationship. Wnt3a and Wnt5a administration or knockdown of DKK-1, a
      Wnt inhibitor, induced BMP-4 and 6 expression and promoter activation in PCa
      cells. DKK-1 blocked Wnt activation of the BMP promoters. Transfection of C4-2B
      cells with axin, an inhibitor of canonical Wnt signaling, blocked Wnt3a but not
      Wnt5a induction of the BMP promoters. In contrast, Jnk inhibitor I blocked Wnt5a
      but not Wnt3a induction of the BMP promoters. Wnt3a, Wnt5a, and conditioned
      medium (CM) from C4-2B or LuCaP23.1 cells induced osteoblast differentiation in
      vitro. The addition of DKK-1 and Noggin, a BMP inhibitor, to CM diminished PCa CM
      induced osteoblast differentiation in a synergistic fashion. However,
      pretreatment of PCa cells with DKK-1 before collecting CM blocked osteoblast
      differentiation, whereas pretreatment with Noggin only partially reduced
      osteoblast differentiation, and pretreatment with both DKK-1 and Noggin had no
      greater effect than pretreatment with DKK-1 alone. Additionally, knockdown of BMP
      expression in C4-2B cells inhibited Wnt-induced osteoblastic activity. These
      results show that PCa promotes osteoblast differentiation through canonical and
      noncanonical Wnt signaling pathways that stimulate both BMP-dependent and BMP
      independent osteoblast differentiation. These results show a clear link between
      Wnts and BMPs in PCa-induced osteoblast differentiation and provide novel
      targets, including the noncanonical Wnt pathway, for therapy of PCa.

PMID- 18632633
TI  - Regulation of the adenomatous polyposis coli gene by the miR-135 family in
      colorectal cancer.
AB  - Inactivation of the adenomatous polyposis coli (APC) gene is a major initiating
      event in colorectal tumorigenesis. Most of the mutations in APC generate
      premature stop codons leading to truncated proteins that have lost beta-catenin
      binding sites. APC-free beta-catenin stimulates the Wnt signaling pathway,
      leading to active transcription of target genes. In the current study, we
      describe a novel mechanism for APC regulation. We show that miR-135a&b target the
      3' untranslated region of APC, suppress its expression, and induce downstream Wnt
      pathway activity. Interestingly, we find a considerable up-regulation of miR
      135a&b in colorectal adenomas and carcinomas, which significantly correlated with
      low APC mRNA levels. This genetic interaction is also preserved in full-blown
      cancer cell lines expressing miR-135a&b, regardless of the mutational status of
      APC. Thus, our results uncover a miRNA-mediated mechanism for the control of APC
      expression and Wnt pathway activity, and suggest its contribution to colorectal
      cancer pathogenesis.

PMID- 18632634
TI  - Cathepsin G enhances mammary tumor-induced osteolysis by generating soluble
      receptor activator of nuclear factor-kappaB ligand.
AB  - Breast cancer commonly causes osteolytic metastases in bone, a process that is
      dependent on tumor-stromal interaction. Proteases play an important role in
      modulating tumor-stromal interactions in a manner that favors tumor establishment
      and progression. Whereas several studies have examined the role of proteases in
      modulating the bone microenvironment, little is currently known about their role
      in tumor-bone interaction during osteolytic metastasis. In cancer-induced
      osteolytic lesions, cleavage of receptor activator of nuclear factor-kappaB
      ligand (RANKL) to a soluble version (sRANKL) is critical for widespread
      osteoclast activation. Using a mouse model that mimics osteolytic changes
      associated with breast cancer-induced bone metastases, we identified cathepsin G,
      cathepsin K, matrix metalloproteinase (MMP)-9, and MMP13 to be proteases that are
      up-regulated at the tumor-bone interface using comparative cDNA microarray
      analysis and quantitative reverse transcription-PCR. Moreover, we showed that
      cathepsin G is capable of shedding the extracellular domain of RANKL, generating
      active sRANKL that is capable of inducing differentiation and activation of
      osteoclast precursors. The major source of cathepsin G at the tumor-bone
      interface seems to be osteoclasts that up-regulate production of cathepsin G via
      interaction with tumor cells. Furthermore, we showed that in vitro
      osteoclastogenesis is reduced by inhibition of cathepsin G in a coculture model
      and that in vivo inhibition of cathepsin G reduces mammary tumor-induced
      osteolysis. Together, our data indicate that cathepsin G activity at the tumor
      bone interface plays an important role in mammary tumor-induced osteolysis and
      suggest that cathepsin G is a potentially novel therapeutic target in the
      treatment of breast cancer bone metastasis.

PMID- 18632635
TI  - The pervasive presence of fluctuating oxygenation in tumors.
AB  - Tumor hypoxia is a persistent obstacle for traditional therapies in solid tumors.
      Strategies for mitigating the effects of hypoxic tumor cells have been developed
      under the assumption that chronically hypoxic tumor cells were the central cause
      of treatment resistance. In this study, we show that instabilities in tumor
      oxygenation are a prevalent characteristic of three tumor lines and previous
      characterization of tumor hypoxia as being primarily diffusion-limited does not
      accurately portray the tumor microenvironment. Phosphorescence lifetime imaging
      was used to measure fluctuations in vascular pO(2) in rat fibrosarcomas, 9L
      gliomas, and R3230 mammary adenocarcinomas grown in dorsal skin-fold window
      chambers (n = 6 for each tumor type) and imaged every 2.5 minutes for a duration
      of 60 to 90 minutes. O(2) delivery to tumors is constantly changing in all
      tumors, resulting in continuous reoxygenation events throughout the tumor.
      Vascular pO(2) maps show significant spatial heterogeneity at each time point, as
      well as between time points. The fluctuations in oxygenation occur with a common
      periodicity within and between tumors, suggesting a common mechanism, but have
      tumor type-dependent spatial patterns. The widespread presence of fluctuations in
      tumor oxygenation has broad ranging implications for tumor progression, stress
      response, and signal transduction, which are altered by oxygenation/reoxygenation
      events.

PMID- 18632636
TI  - Extracellular redox state regulates features associated with prostate cancer cell
      invasion.
AB  - We have examined the possible role of extracellular reduction-oxidation (redox)
      state in regulation of biological/biochemical features associated with prostate
      cancer cell invasion. DU145, PC-3, and RWPE1-derived human prostate cancer (WPE1
      NB26) cell lines were used for the present in vitro analysis. Increasing levels
      of nitric oxide using S-nitroso-N-acetylpenicillamine resulted in a decrease in
      cell invasion ability, whereas increasing levels of extracellular superoxide
      radical (O(2)(*-)) using xanthine/xanthine oxidase resulted in an increase in
      cell invasion ability in these three cell lines. WPE1-NB26 cells exhibited an
      increased glutathione/glutathione disulfide ratio in the medium in comparison
      with RWPE1 cells (immortalized but nonmalignant prostate epithelial cells),
      suggesting an alteration of extracellular redox state of WPE1-NB26 cells. We
      hypothesized that O(2)(*-) production at or near the plasma membrane or in the
      adjacent extracellular matrix at least partially regulated prostate cancer cell
      invasion. Using adenovirus-mediated extracellular superoxide dismutase (EC-SOD)
      gene transduction to enzymatically decrease O(2)(*-) levels, we showed that in
      the presence of heparin, adenovirus EC-SOD gene transduction resulted in an
      increase in the expression of EC-SOD outside the cells with resultant inhibition
      of cell invasion ability. This inhibition correlated with reduced
      metalloproteinase [matrix metalloproteinase (MMP) 2/membrane type 1-MMP]
      activities and increased levels of extracellular nitrite. Our results suggest a
      prominent role of extracellular redox status in regulation of cell invasion,
      which may provide opportunities for therapeutic interventions.

PMID- 18632637
TI  - Hsp90 inhibition suppresses mutant EGFR-T790M signaling and overcomes kinase
      inhibitor resistance.
AB  - The epidermal growth factor receptor (EGFR) secondary kinase domain T790M non
      small cell lung cancer (NSCLC) mutation enhances receptor catalytic activity and
      confers resistance to the reversible tyrosine kinase inhibitors gefitinib and
      erlotinib. Currently, irreversible inhibitors represent the primary approach in
      clinical use to circumvent resistance. We show that higher concentrations of the
      irreversible EGFR inhibitor CL-387,785 are required to inhibit EGFR
      phosphorylation in T790M-expressing cells compared with EGFR mutant NSCLC cells
      without T790M. Additionally, CL-387,785 does not fully suppress phosphorylation
      of other activated receptor tyrosine kinases (RTK) in T790M-expressing cells.
      These deficiencies result in residual Akt and mammalian target of rapamycin
      (mTOR) activities. Full suppression of EGFR-mediated signaling in T790M
      expressing cells requires the combination of CL-387,785 and rapamycin. In
      contrast, Hsp90 inhibition overcomes these limitations in vitro and depletes
      cells of EGFR, other RTKs, and phospho-Akt and inhibits mTOR signaling whether or
      not T790M is present. EGFR-T790M-expressing cells rendered resistant to CL
      387,785 by a kinase switch mechanism retain sensitivity to Hsp90 inhibition.
      Finally, Hsp90 inhibition causes regression in murine lung adenocarcinomas driven
      by mutant EGFR (L858R) with or without T790M. However, efficacy in the L858R
      T790M model requires a more intense treatment schedule and responses were
      transient. Nonetheless, these findings suggest that Hsp90 inhibitors may be
      effective in T790M-expressing cells and offer an alternative therapeutic strategy
      for this subset of lung cancers.

PMID- 18632638
TI  - Activation of platelet-activating factor receptor and pleiotropic effects on
      tyrosine phospho-EGFR/Src/FAK/paxillin in ovarian cancer.
AB  - Among the proinflammatory mediators, platelet-activating factor (PAF, 1-O-alkyl-2
      acetyl-sn-glycero-3-phosphorylcholine) is a major primary and secondary messenger
      involved in intracellular and extracellular communication. Evidence suggests that
      PAF plays a significant role in oncogenic transformation, tumor growth,
      angiogenesis, and metastasis. However, PAF, with its receptor (PAFR) and their
      downstream signaling targets, has not been thoroughly studied in cancer. Here, we
      characterized the PAFR expression pattern in 4 normal human ovarian surface
      epithelial (HOSE) cell lines, 13 ovarian cancer cell lines, paraffin blocks (n =
      84), and tissue microarrays (n = 230) from patients with ovarian cancer.
      Overexpression of PAFR was found in most nonmucinous types of ovarian cancer but
      not in HOSE and mucinous cancer cells. Correspondingly, PAF significantly induced
      cell proliferation and invasion only in PAFR-positive cells (i.e., OVCA429 and
      OVCA432), but not in PAFR-negative ovarian cells (HOSE and mucinous RMUG-L). The
      dependency of cell proliferation and invasion on PAFR was further confirmed using
      PAFR-specific small interfering RNA gene silencing probes, antibodies against
      PAFR and PAFR antagonist, ginkgolide B. Using quantitative multiplex phospho
      antibody array technology, we found that tyrosine phosphorylation of
      EGFR/Src/FAK/paxillin was coordinately activated by PAF treatment, which was
      correlated with the activation of phosphatidylinositol 3-kinase and cyclin D1 as
      markers for cell proliferation, as well as matrix metalloproteinase 2 and 9 for
      invasion. Specific tyrosine Src inhibitor (PP2) reversibly blocked PAF-activated
      cancer cell proliferation and invasion. We suggest that PAFR is an essential
      upstream target of Src and other signal pathways to control the PAF-mediated
      cancer progression.

PMID- 18632639
TI  - Clinical and biological significance of tissue transglutaminase in ovarian
      carcinoma.
AB  - Tissue type transglutaminase (TG2) is a unique multifunctional protein that plays
      a role in many steps in the cancer metastatic cascade. Here, we examined the
      clinical (n = 93 epithelial ovarian cancers) and biological (in vitro adhesion,
      invasion, and survival and in vivo therapeutic targeting) significance of TG2 in
      ovarian cancer. The overexpression of TG2 was associated with significantly worse
      overall patient survival in both univariate and multivariate analyses.
      Transfection of TG2 into SKOV3ip1 cells promoted attachment and spreading on
      fibronectin-coated surfaces and increased the in vitro invasive potential of
      these cells. Conversely, TG2 silencing with small interfering RNA (siRNA) of
      HeyA8 cells significantly decreased the invasive potential of the cells and also
      increased docetaxel-induced cell death. In vivo therapy experiments using
      chemotherapy-sensitive (HeyA8) and chemotherapy-resistant (HeyA8-MDR and RMG2)
      models showed significant antitumor activity both with TG2 siRNA-1,2-dioleoyl-sn
      glycero-3-phosphatidylcholine alone and in combination with docetaxel
      chemotherapy. This antitumor activity was related to decreased proliferation and
      angiogenesis and increased tumor cell apoptosis in vivo. Taken together, these
      findings indicate that TG2 overexpression is an adverse prognostic factor in
      ovarian carcinoma and TG2 targeting may be an attractive therapeutic approach.

PMID- 18632640
TI  - Inhibition of glycogen synthase kinase 3 beta attenuates neurocognitive
      dysfunction resulting from cranial irradiation.
AB  - There are now more than 10 million cancer survivors in the United States. With
      these numbers, chronic sequelae that result from cancer therapy have become a
      major health care problem. Although radiation therapy of the brain has improved
      cancer cure rates, learning disorders and memory deficits are a common
      consequence of this therapy. Here we show that glycogen synthase kinase 3beta
      (GSK-3beta) is required for radiation-induced hippocampal neuronal apoptosis and
      subsequent neurocognitive decline. Inhibition of GSK-3beta either by small
      molecules (SB216763 or SB415286) or by ectopic expression of kinase-inactive GSK
      3beta before irradiation significantly attenuated radiation-induced apoptosis in
      hippocampal neurons. GSK-3beta inhibition with SB216763 or SB415286 also
      decreased apoptosis in the subgranular zone of the hippocampus in irradiated
      mice, leading to improved cognitive function in irradiated animals. Studies of
      the molecular mechanisms of the cytoprotective effect showed that GSK-3beta
      activity in hippocampal neurons was not significantly altered by radiation,
      pointing to the indirect involvement of this enzyme in radiation-induced
      apoptosis. At the same time, radiation led to increased accumulation of p53,
      whereas inhibition of the basal level of GSK-3beta activity before radiation
      prevented p53 accumulation, suggesting a possible mechanism of cytoprotection by
      GSK-3beta inhibitors. These findings identify GSK-3beta signaling as a key
      regulator of radiation-induced damage in hippocampal neurons and suggest that GSK
      3beta inhibitors may have a therapeutic role in protecting both pediatric and
      adult cancer patients and may help to improve quality of life in cancer
      survivors.

PMID- 18632641
TI  - Human endogenous retrovirus K triggers an antigen-specific immune response in
      breast cancer patients.
AB  - Recent evidence indicates that human cancer cells reactivate the expression of
      latent human endogenous retroviral (HERV) proteins. However, the extent to which
      cancer patients mount de novo immune responses against expressed HERV elements is
      unclear. In this study, we determined the extent of HERV-K env expression in
      human breast cancer (BC) and whether both humoral and cell-mediated immunity
      against HERV-K can be found in BC patients. We found HERV-K env protein
      expression in 88% of BC (n = 119) but not in normal breast (n = 76) tissues.
      ELISA screening assays detected significant titers of anti-HERV-K env IgG in a
      large proportion of BC patients. T-cell responses against HERV-K were also
      detected in peripheral blood mononuclear cells (PBMC) from BC patients stimulated
      with autologous dendritic cells pulsed with HERV-K env SU antigens. These
      responses included induction of T-cell proliferation (P = 0.0043), IFN-gamma
      production measured by enzyme-linked immunospot (P < 0.0001), and multiplex
      cytokine secretion (P = 0.0033). Multiplex cytokine analysis found a T-helper 1
      cytokine response, including interleukin (IL)-2 (P = 0.0109), IL-6 (P = 0.0396),
      IL-8 (P = 0.0169), and IP-10 (P = 0.0045) secretion during in vitro stimulation
      of BC PBMC with HERV-K antigen. We also found HERV-K-specific CTLs that were
      capable of lysing target cells expressing HERV-K env protein in BC patients but
      not in normal female controls without cancer. These findings suggest that
      retroviral gene products are capable of acting as tumor-associated antigens
      activating both T-cell and B-cell responses in BC patients.

PMID- 18632642
TI  - A central role for HER3 in HER2-amplified breast cancer: implications for
      targeted therapy.
AB  - Epidermal growth factor receptor (EGFR) and HER3 each form heterodimers with HER2
      and have independently been implicated as key coreceptors that drive HER2
      amplified breast cancer. Some studies suggest a dominant role for EGFR, a notion
      of renewed interest given the development of dual HER2/EGFR small-molecule
      inhibitors. Other studies point to HER3 as the primary coreceptor. To clarify the
      relative contributions of EGFR and HER3 to HER2 signaling, we studied receptor
      knockdown via small interfering RNA technology across a panel of six HER2
      overexpressing cell lines. Interestingly, HER3 was as critical as HER2 for
      maintaining cell proliferation in most cell lines, whereas EGFR was dispensable.
      Induction of HER3 knockdown in the HER2-overexpressing BT474M1 cell line was
      found to inhibit growth in three-dimensional culture and induce rapid tumor
      regression of in vivo xenografts. Furthermore, preferential phosphorylation of
      HER3, but not EGFR, was observed in HER2-amplified breast cancer tissues. Given
      these data suggesting HER3 as an important therapeutic target, we examined the
      activity of pertuzumab, a HER2 antibody that inhibits HER3 signaling by blocking
      ligand-induced HER2/HER3 heterodimerization. Pertuzumab inhibited ligand
      dependent morphogenesis in three-dimensional culture and induced tumor regression
      in the heregulin-dependent MDA-MB-175 xenograft model. Importantly, these
      activities of pertuzumab were distinct from those of trastuzumab, a monoclonal
      antibody currently used for treatment of HER2-amplified breast cancer patients.
      Our data suggest that inhibition of HER3 may be more clinically relevant than
      inhibition of EGFR in HER2-amplified breast cancer and also suggest that adding
      pertuzumab to trastuzumab may augment therapeutic benefit by blocking HER2/HER3
      signaling.

PMID- 18632643
TI  - Atypical protein kinase C iota expression and aurothiomalate sensitivity in human
      lung cancer cells.
AB  - The antirheumatoid agent aurothiomalate (ATM) is a potent inhibitor of oncogenic
      PKC iota. ATM inhibits non-small lung cancer (NSCLC) growth by binding PKC iota
      and blocking activation of a PKC iota-Par6-Rac1-Pak-Mek 1,2-Erk 1,2 signaling
      pathway. Here, we assessed the growth inhibitory activity of ATM in a panel of
      human cell lines representing major lung cancer subtypes. ATM inhibited anchorage
      independent growth in all lines tested with IC(50)s ranging from approximately
      300 nmol/L to >100 micromol/L. ATM sensitivity correlates positively with
      expression of PKC iota and Par6, but not with the PKC iota binding protein p62,
      or the proposed targets of ATM in rheumatoid arthritis (RA), thioredoxin
      reductase 1 or 2. PKC iota expression profiling revealed that a significant
      subset of primary NSCLC tumors express PKC iota at or above the level associated
      with ATM sensitivity. ATM sensitivity is not associated with general sensitivity
      to the cytotoxic agents cis-platin, placitaxel, and gemcitabine. ATM inhibits
      tumorigenicity of both sensitive and insensitive lung cell tumors in vivo at
      plasma drug concentrations achieved in RA patients undergoing ATM therapy. ATM
      inhibits Mek/Erk signaling and decreases proliferative index without effecting
      tumor apoptosis or vascularization in vivo. We conclude that ATM exhibits potent
      antitumor activity against major lung cancer subtypes, particularly tumor cells
      that express high levels of the ATM target PKC iota and Par6. Our results
      indicate that PKC iota expression profiling will be useful in identifying lung
      cancer patients most likely to respond to ATM therapy in an ongoing clinical
      trial.

PMID- 18632644
TI  - Macrophage depletion combined with anticoagulant therapy increases therapeutic
      window of systemic treatment with oncolytic adenovirus.
AB  - Liver tropism of systemically delivered adenoviruses (Ad) represents a
      considerable challenge for their use as anticancer therapeutics. More than 90% of
      i.v. injected Ad is rapidly taken up by the liver leading to hepatotoxicity,
      reduced virus uptake by target tumor tissue, and diminished therapeutic efficacy.
      The lack of clinical activity of systemically given oncolytic Ad demands for
      better understanding and improvement of virus pharmacokinetics. We studied the
      effects of Ad "detargeting" from liver macrophages (Kupffer cells) and
      hepatocytes on toxicity and anticancer efficacy using a nonattenuated oncolytic
      Ad expressing enhanced green fluorescent protein-firefly luciferase fusion
      protein (Ad-EGFPLuc). Kupffer cell depletion before i.v. injection of Ad-EGFPLuc
      increased transgene expression in the liver 40.7-fold on day 3 after the
      injection indicating compensatory enhancement of hepatocyte transduction due to
      increased bioavailability of the virus. Pretreatment of mice with the
      anticoagulant drug warfarin to block blood factor-dependent binding of the virus
      to hepatocytes markedly reduced luciferase expression in the liver and mediated
      the corresponding decrease of hepatotoxicity in mice with intact and depleted
      liver macrophages. Combined depletion of Kupffer cells and pretreatment with
      warfarin before a single i.v. injection of Ad-EGFPLuc significantly reduced tumor
      growth and prolonged survival of nude mice bearing subcutaneous xenografts of
      aggressive human hepatocellular carcinoma. The improved antitumor activity
      correlated with enhanced transgene expression and virus spread in the tumors.
      These data suggest that detargeting oncolytic Ad from liver macrophages and
      hepatocytes is an effective strategy to increase the therapeutic window for
      therapy against disseminated tumor sites.

PMID- 18632645
TI  - The novel angiogenic inhibitor, angiocidin, induces differentiation of monocytes
      to macrophages.
AB  - We previously showed that angiocidin, a tumor and vascular associated protein, is
      a potent inhibitor of angiogenesis and tumor growth. Angiocidin is a multidomain
      protein that exerts its antiangiogenic activity through multiple mechanisms,
      including effects on cell matrix interaction. Here, we describe another activity
      of angiocidin that may contribute to its antitumor activity. We show that
      angiocidin activates monocytes to secrete a mixture of proinflammatory cytokines
      and induces them to differentiate into macrophage-like cells. Using the monocytic
      cell line THP-1, we show that angiocidin induces the cells to become adherent and
      phagocytic, express macrophage markers, and secrete matrix metalloproteinase-9.
      Microarray analysis of control and angiocidin-treated THP-1 cells revealed that
      angiocidin up-regulated p105/p50, p100/p52, and rel B, components of the nuclear
      factor-kappaB (NF-kappaB) pathway. We confirmed the microarray data and showed
      that angiocidin induced phosphorylation of I kappa beta, p50, and p65 and
      translocation of p50 and p65 to the nucleus. We also showed that angiocidin
      activated up-stream mediators of NF-kappaB, such as the mitogen-activated protein
      kinase (MAPK) pathway and phosphoinositide-3 kinase (PI3K). Blockage of NF-kappaB
      and MAPK activation with small molecule inhibitors completely prevented
      angiocidin-mediated secretion of cytokines from THP-1 cells, but did not inhibit
      their adhesive phenotype. Blocking PI3K inhibited both secretion of cytokines, as
      well as the adhesive phenotype. These data suggest that angiocidin activates
      monocytes to secrete cytokines and differentiates them to a macrophage-like
      phenotype through at least two pathways mediated by MAPK and NF-kappaB, as well
      as PI3K.

PMID- 18632646
TI  - Class I PI3 kinase inhibition by the pyridinylfuranopyrimidine inhibitor PI-103
      enhances tumor radiosensitivity.
AB  - Cell signaling initiated at the epidermal growth factor receptor (EGFR), RAS
      oncoproteins, or PI3K contributes to a common pathway that promotes tumor
      survival after radiation-induced DNA damage. Inhibition of signaling at the level
      of EGFR, RAS, and PI3K has been tested, but clinical applicability has been shown
      only at the level of the EGFR or by inhibiting RAS indirectly with
      prenyltransferase inhibitors. Inhibition of PI3K with LY294002 or wortmannin
      lacks specificity and has shown unacceptable toxicity in preclinical studies. We
      previously showed that inhibiting class I PI3K expression with siRNA resulted in
      enhanced radiation killing of tumor cells. Here, we tested the possibility of
      achieving specific tumor cell radiosensitization with a pharmacologic inhibitor
      of class I PI3K, the pyridinylfuranopyrimidine inhibitor PI-103. Our results show
      that inhibiting PI3K activity reduces phosphorylation of AKT at serine 473.
      Reduced survival is seen in cells with AKT activation and seems preferential for
      tumor cells over cells in which AKT activity is not elevated. Reduced survival is
      accompanied by persistence of DNA damage as evidenced by persistence of gamma
      H2AX and Rad 51 foci after irradiation in the presence of the inhibitor. Reduced
      survival does not result from cell cycle redistribution during the PI-103
      treatment intervals tested, although combining PI-103 treatment with radiation
      enhances the G(2)-M delay observed after irradiation. These results indicate that
      pharmacologic inhibitors with enhanced specificity for class I PI3K may be of
      benefit when combined with radiotherapy.

PMID- 18632647
TI  - Cell lineage analysis of a mouse tumor.
AB  - Revealing the lineage relations among cancer cells can shed light on tumor growth
      patterns and metastasis formation, yet cell lineages have been difficult to come
      by in the absence of a suitable method. We previously developed a method for
      reconstructing cell lineage trees from genomic variability caused by somatic
      mutations. Here, we apply the method to cancer and reconstruct, for the first
      time, a lineage tree of neoplastic and adjacent normal cells obtained by laser
      microdissection from tissue sections of a mouse lymphoma. Analysis of the
      reconstructed tree reveals that the tumor initiated from a single founder cell,
      approximately 5 months before diagnosis, that the tumor grew in a physically
      coherent manner, and that the average number of cell divisions accumulated in
      cancerous cells was almost twice than in adjacent normal lung epithelial cells
      but slightly less than the expected figure for normal B lymphocytes. The cells
      were also genotyped at the TP53 locus, and neoplastic cells were found to share a
      common mutation, which was most likely present in a heterozygous state. Our work
      shows that the ability to obtain data regarding the physical appearance, precise
      anatomic position, genotypic profile, and lineage position of single cells may be
      useful for investigating cancer development, progression, and interaction with
      the microenvironment.

PMID- 18632648
TI  - Noninvasive assessment of E2F-1-mediated transcriptional regulation in vivo.
AB  - Targeted therapies directed against individual cancer-specific molecular
      alterations offer the development of disease-specific and individualized
      treatment strategies. Activation of the transcription factor E2F-1 via alteration
      of the p16-cyclinD-Rb pathway is one of the key molecular events in the
      development of gliomas. E2F-1 binds to and activates the E2F-1 promoter in an
      autoregulatory manner. The human E2F-1 promoter has been shown to be selectively
      activated in tumor cells with a defect in the pRb pathway. Paradoxically, E2F-1
      also carries tumor suppressor function. Our investigations focused on analyzing
      the dynamics of the activity of the E2F-1 responsive element under basal
      conditions and certain stimuli such as chemotherapy using molecular imaging
      technology. We constructed a retrovirus bearing the Cis-E2F-TA-LITG reporter
      system to noninvasively assess E2F-1-dependent transcriptional regulation in
      culture and in vivo. We show that our reporter system is sensitive to monitor
      various changes in cellular E2F-1 levels and its transcriptional control of our
      reporter system to follow the state of the Rb/E2F pathway and the DNA damage
      induced up-regulation of E2F-1 activity in vivo. Exposure to 1,3-bis(2
      chloroethyl)-1-nitrosourea leads to increased E2F-1 expression levels in a dose-
      and time-dependent manner, which can be quantified by imaging in vivo, leading to
      an alteration of cell cycle progression and caspase 3/7 activity. In summary,
      noninvasive imaging of E2F-1 as a common downstream regulator of cell cycle
      progression using the Cis-E2F-TA-LUC-IRES-TKGFP reporter system is highly
      attractive for evaluating the kinetics of cell cycle regulation and the effects
      of novel cell cycle targeting anticancer agents in vivo.

PMID- 18632649
TI  - New insights into tumor microstructure using temporal diffusion spectroscopy.
AB  - Magnetic resonance images (MRI) that depict rates of water diffusion in tissues
      can be used to characterize the cellularity of tumors and are valuable in
      assessing their early response to treatment. Water diffusion rates are sensitive
      to the cellular and molecular content of tissues and are affected by local
      microstructural changes associated with tumor development. However, conventional
      maps of water diffusion reflect the integrated effects of restrictions to free
      diffusion at multiple scales up to a specific limiting spatial dimension,
      typically several micrometers. Such measurements cannot distinguish effects
      caused by structural variations at a smaller scale. Variations in diffusion rates
      then largely reflect variations in the density of cells, and no information is
      available about changes on a subcellular scale. We report here our experiences
      using a new approach based on Oscillating Gradient Spin-Echo (OGSE) MRI methods
      that can differentiate the influence on water diffusion of structural changes on
      scales much smaller than the diameter of a single cell. MRIs of glioblastomas in
      rat brain in vivo show an increased contrast and spatial heterogeneity when
      diffusion measurements are selectively sensitized to shorter distance scales.
      These results show the benefit of OGSE methods for revealing microscopic
      variations in tumors in vivo and confirm that diffusion measurements depend on
      factors other than cellularity.

PMID- 18632650
TI  - Regulatory T cell-resistant CD8+ T cells induced by glucocorticoid-induced tumor
      necrosis factor receptor signaling.
AB  - We previously found that a Salmonella typhimurium vector engineered to secrete
      soluble tumor antigen induces CD4(+) T cells resistant to CD4(+)CD25(+)
      regulatory T cells (Treg) and that glucocorticoid-induced tumor necrosis factor
      receptor family-related gene (GITR) signal is involved in the development of this
      resistance. In this study, we address the potential of incorporating GITR ligand
      (GITRL) as a way to augment the immunogenicity of cancer vaccines. BALB/c mice
      were immunized by gene gun with plasmids encoding the mutated extracellular
      signal-regulated kinase 2 (mERK) with or without plasmids encoding mouse GITRL.
      Coadministration with GITRL during primary and secondary immunization enhanced
      the induction of mERK-specific CD8(+) T cells. Antibody depletion and minigene
      analysis suggested that GITRL directly activated CTL epitope-specific CD8(+) T
      cells independently of CD4(+) T cells. Immunization with plasmids encoding a CTL
      epitope and GITRL resulted in strong tumor inhibition in a CD8(+) T cell
      dependent manner. Furthermore, CTL epitope-specific CD8(+) T cells induced by
      immunization with plasmids encoding CTL epitope coadministered with GITRL were
      refractory to suppression by CD4(+)CD25(+) Tregs compared with CD8(+) T cells
      induced without GITR signaling. We propose that coadministration of GITR
      signaling agents with tumor antigens constitutes a promising novel strategy for
      cancer vaccine development.

PMID- 18632651
TI  - Vaccination elicits correlated immune and clinical responses in glioblastoma
      multiforme patients.
AB  - Cancer vaccine trials have failed to yield robust immune-correlated clinical
      improvements as observed in animal models, fueling controversy over the utility
      of human cancer vaccines. Therapeutic vaccination represents an intriguing
      additional therapy for glioblastoma multiforme (GBM; grade 4 glioma), which has a
      dismal prognosis and treatment response, but only early phase I vaccine trial
      results have been reported. Immune and clinical responses from a phase II GBM
      vaccine trial are reported here. IFN-gamma responsiveness was quantified in
      peripheral blood of 32 GBM patients given therapeutic dendritic cell vaccines.
      Posttreatment times to tumor progression (TTP) and survival (TTS) were compared
      in vaccine responders and nonresponders and were correlated with immune response
      magnitudes. GBM patients (53%) exhibited >or=1.5-fold vaccine-enhanced cytokine
      responses. Endogenous antitumor responses of similar magnitude occurred in 22% of
      GBM patients before vaccination. Vaccine responders exhibited significantly
      longer TTS and TTP relative to nonresponders. Immune enhancement in vaccine
      responders correlated logarithmically with TTS and TTP spanning postvaccine
      chemotherapy, but not with initial TTP spanning vaccination alone. This is the
      first report of a progressive correlation between cancer clinical outcome and T
      cell responsiveness after therapeutic vaccination in humans and the first tracing
      of such correlation to therapeutically exploitable tumor alteration. As such, our
      findings offer unique opportunities to identify cellular and molecular components
      of clinically meaningful antitumor immunity in humans.

PMID- 18632652
TI  - Recruitment and activation of natural killer cells in vitro by a human dendritic
      cell vaccine.
AB  - Recruitment of circulating natural killer (NK) cells into inflamed lymph nodes is
      known to provide a potent, IFN-gamma-dependent boost for Th1-polarized immune
      responses in mouse models. Such NK cell recruitment into draining lymph nodes is
      induced by certain s.c. injected adjuvants, including mature vaccine dendritic
      cells (DC), and is mediated by a CXCR3-dependent pathway. Here, we show that
      monocyte-derived immature human DCs stimulated with polyinosinic
      acid:polycytidylic acid, IFN-alpha, tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta), and IFN-gamma, alpha-type 1-polarized DC (alpha
      DC1), secrete profuse amounts of the CXCR3 ligand CXCL9/MIG and substantial
      amounts of CXCL10/IP-10 and CXCL11/I-TAC after withdrawal of maturation stimuli.
      In sharp contrast, no measurable production of these chemokines was found in DCs
      after maturation with the current gold standard maturation cocktail for human DC
      based cancer vaccines consisting of TNF-alpha, IL-1 beta, IL-6, and prostaglandin
      E(2) (PGE(2)-DC). PGE(2)-DCs preferentially produced the Th2 and regulatory T
      cell-attracting chemokines CCL17/TARC and CCL22/MDC, whereas only marginal levels
      of these chemokines were produced by alpha DC1s. Functional studies in vitro
      showed that supernatants from mature alpha DC1s actively recruited CD3(-)CD56(+)
      NK cells and that adding anti-CXCL9/MIG antibodies to the alpha DC1 supernatant
      substantially reduced this recruitment. Finally, alpha DC1s were able to induce
      IFN-gamma production when cocultured with resting autologous NK cells, but only
      if concurrent CD40 ligation was provided. These novel findings indicate that
      injected human alpha DC1-based vaccines have the potential to recruit and
      activate NK cells during their arrival to draining lymph nodes and that this
      feature may be of relevance for efficient priming of Th1 cells and CTLs.

PMID- 18632653
TI  - Ability of mature dendritic cells to interact with regulatory T cells is
      imprinted during maturation.
AB  - Preferential activation of regulatory T (Treg) cells limits autoimmune tissue
      damage during chronic immune responses but can also facilitate tumor growth.
      Here, we show that tissue-produced inflammatory mediators prime maturing
      dendritic cells (DC) for the differential ability of attracting anti-inflammatory
      Treg cells. Our data show that prostaglandin E(2) (PGE(2)), a factor overproduced
      in chronic inflammation and cancer, induces stable Treg-attracting properties in
      maturing DC, mediated by CCL22. The elevated production of CCL22 by PGE(2)
      matured DC persists after the removal of PGE(2) and is further elevated after
      secondary stimulation of DC in a neutral environment. This PGE(2)-induced
      overproduction of CCL22 and the resulting attraction of FOXP3(+) Tregs are
      counteracted by IFN alpha, a mediator of acute inflammation, which also restores
      the ability of the PGE(2)-exposed DC to secrete the Th1-attracting chemokines:
      CXCL9, CXCL10, CXCL11, and CCL5. In accordance with these observations, different
      DCs clinically used as cancer vaccines show different Treg-recruiting abilities,
      with PGE(2)-matured DC, but not type 1-polarized DC, generated in the presence of
      type I and type II IFNs, showing high Treg-attracting activity. The current data,
      showing that the ability of mature DC to interact with Treg cells is
      predetermined at the stage of DC maturation, pave the way to preferentially
      target the regulatory versus proinflammatory T cells in autoimmunity and
      transplantation, as opposed to intracellular infections and cancer.

PMID- 18632654
TI  - Modulation of CD59 expression by restrictive silencer factor-derived peptides in
      cancer immunotherapy for neuroblastoma.
AB  - Tumor cells escape clearance by complement by abundantly expressing CD59 and
      other membrane complement regulators. Existing strategies for blocking/knocking
      down these regulators can contribute to tumor immunoclearance in vitro; however,
      there are numerous difficulties restricting their use in vivo. Here, we report a
      new strategy for suppression of CD59 expression in neuroblastoma using peptides
      that target regulators of CD59 expression. We identified the neural-restrictive
      silencer factor (REST) as a target for modulation of CD59 expression in
      neuroblastoma. We next designed plasmids that encoded peptides comprising
      different DNA-binding domains of REST and transfected them into neuroblastoma
      cell lines. These peptides suppressed CD59 expression, sensitizing neuroblastoma
      to complement-mediated killing triggered by anti-GD2 therapeutic monoclonal
      antibody. These CD59-modulating peptides might be effective therapeutic adjuvants
      to therapeutic monoclonal antibodies used for treatment of neuroblastoma and
      other cancer types sharing the same mechanism for regulation of CD59 expression.

PMID- 18632655
TI  - Hepatitis B virus-associated multistep hepatocarcinogenesis: a stepwise increase
      in allelic alterations.
AB  - Hepatocarcinogenesis is a multistep process, but systematic analysis using a
      genetic or molecular approach to accurately delineate the different stages of
      hepatocellular carcinoma (HCC) development is scarce. In this study, we used
      genome-wide allelotyping to systematically evaluate the allelic alterations in
      the multisteps of hepatitis B virus-associated hepatocarcinogenesis. The overall
      fractional allelic loss (FAL) indices of cirrhosis, dysplastic nodules (DN), and
      HCC were significantly different, with a clear stepwise increase (P < 0.001).
      Loss of heterozygosity (LOH) was uncommon in cirrhotic livers (n = 24; mean FAL
      index +/- SD, 0.09 +/- 0.09; median, 0.07). In contrast, LOH was common in our 74
      HCC nodules, which were predominantly hepatitis B virus-associated (mean FAL
      index +/- SD, 0.40 +/- 0.23; median, 0.38). The 18 DNs had FAL index (mean +/-
      SD, 0.27 +/- 0.19; median, 0.20) in between that of cirrhosis and HCC.
      Importantly, high-grade DNs had FAL index significantly higher than that of low
      grade DNs (P = 0.031) and close to that of HCC, indicating that high-grade DNs
      were genetically closer to HCC. However, there was no significant difference in
      FAL indices between primary HCCs and their corresponding intrahepatic metastases,
      but this absence of major allelic losses in this transformation to a metastatic
      phenotype does not exclude small-scale chromosomal losses or gene deletions. To
      conclude, hepatitis B virus-associated hepatocarcinogenesis is a multistep
      process accompanied by stepwise increase in allelic losses from cirrhosis and low
      and high-grade DN to HCC. Such allelic losses contribute to promote tumor
      development and progression.

PMID- 18632657
TI  - Presence of a TA haplotype in the APC gene containing the common 1822
      polymorphism and colorectal adenoma.
AB  - Acquired or inherited mutations in the adenomatous polyposis coli (APC) tumor
      suppressor gene are causally linked to colorectal cancer. Given the significance
      of APC in colorectal cancer, we investigated the association between common
      single-nucleotide polymorphisms (SNP) in the APC gene and the odds of developing
      metachronous colorectal adenomas as a surrogate measure of colorectal cancer
      risk. Coding SNPs at codons 486, 1678, 1822, 1960, and 2502 were analyzed in a
      total of 1,399 subjects who participated in two randomized clinical trials for
      the prevention of colorectal adenomas. No association was found for any single
      SNP and the odds of metachronous adenoma. In contrast, a TA haplotype (codons 486
      and 1822) was associated with a statistically significant 27% and 26% reduction
      in the odds of any and nonadvanced metachronous adenoma after adjustment for
      baseline adenoma characteristics [odds ratio (OR), 0.73; 95% confidence interval
      (95% CI), 0.59-0.91 and OR, 0.74; 95% CI, 0.57-0.94], respectively. No
      significant reduction in odds was observed for advanced metachronous lesions.
      Diplotype analysis revealed a strong gene dose effect with carriers of two
      alleles containing TT-AA (codons 486 and 1822, respectively) having an 89% lower
      odds for advanced metachronous adenomas (OR, 0.11; 95% CI, 0.01-0.80) when
      compared with the common CC-AA diplotype (codons 486 and 1822, respectively). Our
      findings support an important role for germ-line allele sequence in the APC gene
      and individual risk of metachronous adenomatous polyps.

PMID- 18632656
TI  - Breast cancer risk reduction and membrane-bound catechol O-methyltransferase
      genetic polymorphisms.
AB  - Catechol O-methyltransferase (COMT)-catalyzed methylation of catecholestrogens
      has been proposed to play a protective role in estrogen-induced genotoxic
      carcinogenesis. We have taken a comprehensive approach to test the hypothesis
      that genetic variation in COMT might influence breast cancer risk. Fifteen COMT
      single nucleotide polymorphisms (SNPs) selected on the basis of in-depth
      resequencing of the COMT gene were genotyped in 1,482 DNA samples from a Mayo
      Clinic breast cancer case control study. Two common SNPs in the distal promoter
      for membrane-bound (MB) COMT, rs2020917 and rs737865, were associated with breast
      cancer risk reduction in premenopausal women in the Mayo Clinic study, with
      allele-specific odds ratios (OR) of 0.70 [95% confidence interval (CI), 0.52
      0.95] and 0.68 (95% CI, 0.51-0.92), respectively. These two SNPs were then
      subjected to functional genomic analysis and were genotyped in an additional
      3,683 DNA samples from two independent case control studies (GENICA and GESBC).
      Functional genomic experiments showed that these SNPs could up-regulate
      transcription and that they altered DNA-protein binding patterns. Furthermore,
      substrate kinetic and exon array analyses suggested a role for MB-COMT in
      catecholestrogen inactivation. The GENICA results were similar to the Mayo case
      control observations, with ORs of 0.85 (95% CI, 0.72-1.00) and 0.85 (95% CI, 0.72
      1.01) for the two SNPs. No significant effect was observed in the GESBC study.
      These studies showed that two SNPs in the COMT distal promoter were associated
      with breast cancer risk reduction in two of three case control studies,
      compatible with the results of functional genomic experiments, suggesting a role
      for MB-COMT in breast cancer risk.

PMID- 18632658
TI  - PTEN expression in endometrial biopsies as a marker of progression to endometrial
      carcinoma.
AB  - Inactivation of PTEN tumor suppressor gene is common in endometrial carcinoma and
      its precursor, atypical endometrial hyperplasia (EH). We compared PTEN expression
      via immunohistochemistry in endometrial biopsies diagnosed as EH in 138 cases,
      who were diagnosed with EH and then endometrial carcinoma at least 1 year later
      (median, 6 years), and 241 individually matched controls, who were diagnosed with
      EH but did not progress to carcinoma during equivalent follow-up. We assessed
      PTEN status (normal versus null) in index biopsies containing EH to estimate the
      relative risk (RR) of developing endometrial carcinoma up to 25 years later.
      Analysis of 115 cases and 193 controls with satisfactory assays revealed PTEN
      null glands in index biopsies of 44% of cases and 49% of controls [P = 0.85; RR,
      1.51; 95% confidence interval (CI), 0.73-3.13]. For predicting progression to
      carcinoma, PTEN-null status had low sensitivity (44%; 95% CI, 45-54%) and
      specificity (51%; 95% CI, 44-58%). Among 105 cases with PTEN results for both
      index biopsy and carcinoma, 16% had a PTEN-null index biopsy, 23% had PTEN-null
      carcinoma, and 26% had both a PTEN-null index biopsy and carcinoma. Loss of PTEN
      expression in endometrial biopsies was neither associated with nor a sensitive
      and specific marker of subsequent progression to endometrial carcinoma.

PMID- 18632659
TI  - Myricetin suppresses UVB-induced skin cancer by targeting Fyn.
AB  - Skin cancer is currently the most common type of human cancer in Americans.
      Myricetin, a naturally occurring phytochemical, has potent anticancer-promoting
      activity and contributes to the chemopreventive potential of several foods,
      including red wine. Here, we show that myricetin suppresses UVB-induced
      cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The
      activation of activator protein-1 and nuclear factor-kappaB induced by UVB was
      dose-dependently inhibited by myricetin treatment. Western blot and kinase assay
      data revealed that myricetin inhibited Fyn kinase activity and subsequently
      attenuated UVB-induced phosphorylation of mitogen-activated protein kinases. Pull
      down assays revealed that myricetin competitively bound with ATP to suppress Fyn
      kinase activity. Importantly, myricetin exerted similar inhibitory effects
      compared with 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, a
      well-known pharmacologic inhibitor of Fyn. In vivo mouse skin data also revealed
      that myricetin inhibited Fyn kinase activity directly and subsequently attenuated
      UVB-induced COX-2 expression. Mouse skin tumorigenesis data clearly showed that
      pretreatment with myricetin significantly suppressed UVB-induced skin tumor
      incidence in a dose-dependent manner. Docking data suggest that myricetin is
      easily docked to the ATP-binding site of Fyn, which is located between the N and
      C lobes of the kinase domain. Overall, these results indicated that myricetin
      exerts potent chemopreventive activity mainly by targeting Fyn in skin
      carcinogenesis.

PMID- 18632660
TI  - Adiponectin blocks interleukin-18-mediated endothelial cell death via APPL1
      dependent AMP-activated protein kinase (AMPK) activation and IKK/NF-kappaB/PTEN
      suppression.
AB  - The adipocyte-derived cytokine adiponectin is known to exert anti-inflammatory
      and anti-apoptotic effects. In patients with atherosclerotic cardiovascular
      disease, circulating levels of adiponectin correlate inversely with those of the
      proinflammatory, proapoptotic cytokine interleukin (IL)-18. The opposing actions
      of IL-18 and adiponectin on both cell survival and inflammation led us to
      investigate whether adiponectin signaling antagonizes IL-18-mediated endothelial
      cell death and to identify the underlying molecular mechanisms. Treatment with IL
      18 suppressed Akt phosphorylation and its associated kinase activity, induced
      IkappaB kinase (IKK)-NF-kappaB-dependent PTEN activation, and promoted
      endothelial cell death. Pretreatment with adiponectin stimulated APPL1-dependent
      AMPK activation, reversed Akt inhibition in a phosphatidylinositol 3-kinase
      dependent manner, blocked IKK-NF-kappaB-PTEN signaling, reduced caspase-3
      activity, blocked Bax translocation, and inhibited endothelial cell death. The
      cytoprotective effect of adiponectin signaling was recapitulated by treatment
      with the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide-1-beta
      riboside. Collectively, these results demonstrated that adiponectin reverses IL
      18-mediated endothelial cell death through an AMPK-associated mechanism, which
      may thus have therapeutic potential for diminishing IL-18-dependent vascular
      injury and inflammation.

PMID- 18632662
TI  - Regulation of nuclear Ca2+ signaling by translocation of the Ca2+ messenger
      synthesizing enzyme ADP-ribosyl cyclase during neuronal depolarization.
AB  - In neurons, voltage-gated Ca(2+) channels and nuclear Ca(2+) signaling play
      important roles, such as in the regulation of gene expression. However, the link
      between electrical activity and biochemical cascade activation involved in the
      generation of the nuclear Ca(2+) signaling is poorly understood. Here we show
      that depolarization of Aplysia neurons induces the translocation of ADP-ribosyl
      cyclase, a Ca(2+) messenger synthesizing enzyme, from the cytosol into the
      nucleus. The translocation is dependent on Ca(2+) influx mainly through the
      voltage-dependent L-type Ca(2+) channels. We report also that specific
      nucleoplasmic Ca(2+) signals can be induced by three different calcium
      messengers, cyclic ADP-ribose, nicotinic acid adenine dinucleotide phosphate
      (NAADP), both produced by the ADP-ribosyl cyclase, and inositol 1,4,5
      trisphosphate (IP(3)). Moreover, our pharmacological data show that NAADP acts on
      its own receptor, which cooperates with the IP(3) and the ryanodine receptors to
      generate nucleoplasmic Ca(2+) oscillations. We propose a new model where voltage
      dependent L-type Ca(2+) channel-induced nuclear translocation of the cytosolic
      cyclase is a crucial step in the fine tuning of nuclear Ca(2+) signals in
      neurons.

PMID- 18632661
TI  - CAATT/enhancer-binding proteins alpha and delta interact with NKX2-1 to
      synergistically activate mouse secretoglobin 3A2 gene expression.
AB  - Secretoglobin (SCGB) 3A2 is a small molecular weight secreted protein
      predominantly expressed in lung airways. We previously demonstrated that the
      expression of SCGB3A2 is regulated by homeodomain transcription factor NKX2-1.
      Here we show that CCAAT/enhancer-binding proteins, C/EBPalpha and C/EBPdelta,
      regulate mouse Scgb3a2 gene transcription in vivo and in vitro by binding to
      specific sites located in the Scgb3a2 promoter and the activity is
      synergistically enhanced through cooperative interaction with NKX2-1. Six C/EBP
      binding sites lie within 500 bp of the Scgb3a2 gene promoter, of which two sites,
      located at -44 to -54 bp and -192 to -201 bp, appear to be critical for the
      synergistic activation of Scgb3a2 gene transcription with NKX2-1. All three
      transcription factors, C/EBPalpha, C/EBPdelta, and NKX2-1, are expressed in the
      epithelial cells of airways, particularly the bronchus, where high expression of
      SCGB3A2 is found. The expression of these transcription factors markedly
      increases toward the end of gestation, which coincides with the marked increase
      of SCGB3A2, suggesting the importance of C/EBPalpha and C/EBPdelta, and their
      synergistic interaction with NKX2-1 in mouse Scgb3a2 gene transcription and lung
      development.

PMID- 18632663
TI  - Systematic structure-activity analysis of microcin J25.
AB  - Microcin J25 (MccJ25) is a 21-residue plasmid-encoded ribosomally synthesized
      lariat-protoknot antibacterial peptide that targets bacterial RNA polymerase.
      MccJ25 consists of an 8-residue cycle followed by a 13-residue tail that loops
      back and threads through the cycle. We have performed systematic mutational
      scanning of MccJ25, constructing and analyzing more than 380 singly substituted
      derivatives of MccJ25. The results define residues important for production of
      MccJ25 (comprising synthesis of MccJ25 precursor, processing of MccJ25 precursor,
      export of mature MccJ25, and stability of mature MccJ25), inhibition of RNA
      polymerase, and inhibition of bacterial growth. The results show that only a
      small number of residues (three in the cycle and one in the threaded segment of
      the tail) are important for MccJ25 production. The results further show that only
      a small number of additional residues (two in the cycle and four in the threaded
      segment of the tail) are important for inhibition of transcription. The results
      open the way for design and construction of more potent MccJ25-based inhibitors
      of bacterial growth.

PMID- 18632664
TI  - Structural organization of photosynthetic apparatus in agranal chloroplasts of
      maize.
AB  - We investigated the organization of photosystem II (PSII) in agranal bundle
      sheath thylakoids from a C(4) plant maize. Using blue native/SDS-PAGE and single
      particle analysis, we show for the first time that PSII in the bundle sheath (BS)
      chloroplasts exists in a dimeric form and forms light-harvesting complex II
      (LHCII).PSII supercomplexes. We also demonstrate that a similar set of
      photosynthetic membrane complexes exists in mesophyll and agranal BS
      chloroplasts, including intact LHCI.PSI supercomplexes, PSI monomers, PSII core
      dimers, PSII monomers devoid of CP43, LHCII trimers, LHCII monomers, ATP
      synthase, and cytochrome b(6)f complex. Fluorescence functional measurements
      clearly indicate that BS chloroplasts contain PSII complexes that are capable of
      performing charge separation and are efficiently sensitized by the associated
      LHCII. We identified a fraction of LHCII present within BS thylakoids that is
      weakly energetically coupled to the PSII reaction center; however, the majority
      of BS LHCII is shown to be tightly connected to PSII. Overall, we demonstrate
      that organization of the photosynthetic apparatus in BS agranal chloroplasts of a
      model C(4) plant is clearly distinct from that of the stroma lamellae of the C(3)
      plants. In particular, supramolecular organization of the dimeric LHCII.PSII in
      the BS thylakoids strongly suggests that PSII in the BS agranal membranes may
      donate electrons to PSI. We propose that the residual PSII activity may supply
      electrons to poise cyclic electron flow around PSI and prevent PSI overoxidation,
      which is essential for the CO(2) fixation in BS cells, and hence, may optimize
      ATP production within this compartment.

PMID- 18632665
TI  - The human escort protein Hep binds to the ATPase domain of mitochondrial hsp70
      and regulates ATP hydrolysis.
AB  - Hsp70 escort proteins (Hep) have been implicated as essential for maintaining the
      function of yeast mitochondrial hsp70 molecular chaperones (mtHsp70), but the
      role that escort proteins play in regulating mammalian chaperone folding and
      function has not been established. We present evidence that human mtHsp70
      exhibits limited solubility due to aggregation mediated by its ATPase domain and
      show that human Hep directly enhances chaperone solubility through interactions
      with this domain. In the absence of Hep, mtHsp70 was insoluble when expressed in
      Escherichia coli, as was its isolated ATPase domain and a chimera having this
      domain fused to the peptide-binding domain of HscA, a soluble monomeric
      chaperone. In contrast, these proteins all exhibited increased solubility when
      expressed in the presence of Hep. In vitro studies further revealed that purified
      Hep regulates the interaction of mtHsp70 with nucleotides. Full-length mtHsp70
      exhibited slow intrinsic ATP hydrolysis activity (6.8+/-0.2 x 10(-4) s(-1)) at 25
      degrees C, which was stimulated up to 49-fold by Hep. Hep also stimulated the
      activity of the isolated ATPase domain, albeit to a lower maximal extent (11.5
      fold). In addition, gel-filtration studies showed that formation of chaperone
      escort protein complexes inhibited mtHsp70 self-association, and they revealed
      that Hep binding to full-length mtHsp70 and its isolated ATPase domain is
      strongest in the absence of nucleotides. These findings provide evidence that
      metazoan escort proteins regulate the catalytic activity and solubility of their
      cognate chaperones, and they indicate that both forms of regulation arise from
      interactions with the mtHsp70 ATPase domain.

PMID- 18632666
TI  - A new iron-oxidizing/O2-reducing supercomplex spanning both inner and outer
      membranes, isolated from the extreme acidophile Acidithiobacillus ferrooxidans.
AB  - The iron respiratory chain of the acidophilic bacterium Acidithiobacillus
      ferrooxidans involves various metalloenzymes. Here we demonstrate that the oxygen
      reduction pathway from ferrous iron (named downhill pathway) is organized as a
      supercomplex constituted of proteins located in the outer and inner membranes as
      well as in the periplasm. For the first time, the outer membrane-bound cytochrome
      c Cyc2 was purified, and we showed that it is responsible for iron oxidation and
      determined that its redox potential is the highest measured to date for a
      cytochrome c. The organization of metalloproteins inside the supramolecular
      structure was specified by protein-protein interaction experiments. The isolated
      complex spanning the two membranes had iron oxidase as well as oxygen reductase
      activities, indicating functional electron transfer between the first iron
      electron acceptor, Cyc2, and the Cu(A) center of cytochrome c oxidase aa(3). This
      is the first characterization of a respirasome from an acidophilic bacterium. In
      Acidithiobacillus ferrooxidans,O(2) reduction from ferrous iron must be coupled
      to the energy-consuming reduction of NAD(+)(P) from ferrous iron (uphill pathway)
      required for CO(2) fixation and other anabolic processes. Besides the proteins
      involved in the O(2) reduction, there were additional proteins in the
      supercomplex, involved in uphill pathway (bc complex and cytochrome Cyc(42)),
      suggesting a possible physical link between these two pathways.

PMID- 18632667
TI  - Pivotal role of Bcl-2 family proteins in the regulation of chondrocyte apoptosis.
AB  - During endochondral ossification, chondrocytes undergo hypertrophic
      differentiation and die by apoptosis. The level of inorganic phosphate (P(i))
      elevates at the site of cartilage mineralization, and when chondrocytes were
      treated with P(i), they underwent rapid apoptosis. Gene silencing of the
      proapoptotic Bcl-2 homology 3-only molecule bnip3 significantly suppressed P(i)
      induced apoptosis. Conversely, overexpression of Bcl-xL suppressed, and its
      knockdown promoted, the apoptosis of chondrocytes. Bnip3 was associated with Bcl
      xL in chondrocytes stimulated with P(i). Bcl-xL was expressed uniformly in the
      growth plate chondrocytes, whereas Bnip3 expression was exclusively localized in
      the hypertrophic chondrocytes. Finally, we generated chondrocyte-specific bcl-x
      knock-out mice using the Cre-loxP recombination system, and we provided evidence
      that the hypertrophic chondrocyte layer was shortened in those mice because of an
      increased apoptosis of prehypertrophic and hypertrophic chondrocytes, with the
      mice afflicted with dwarfism as a result. These results suggest the pivotal role
      of Bcl-2 family members in the regulation of chondrocyte apoptosis.

PMID- 18632668
TI  - Group IVA phospholipase A2 is necessary for the biogenesis of lipid droplets.
AB  - Lipid droplets (LD) are organelles present in all cell types, consisting of a
      hydrophobic core of triacylglycerols and cholesteryl esters, surrounded by a
      monolayer of phospholipids and cholesterol. This work shows that LD biogenesis
      induced by serum, by long-chain fatty acids, or the combination of both in CHO-K1
      cells was prevented by phospholipase A(2) inhibitors with a pharmacological
      profile consistent with the implication of group IVA cytosolic phospholipase A(2)
      (cPLA(2)alpha). Knocking down cPLA(2)alpha expression with short interfering RNA
      was similar to pharmacological inhibition in terms of enzyme activity and LD
      biogenesis. A Chinese hamster ovary cell clone stably expressing an enhanced
      green fluorescent protein-cPLA(2)alpha fusion protein (EGFP-cPLA(2)) displayed
      higher LD occurrence under basal conditions and upon LD induction. Induction of
      LD took place with concurrent phosphorylation of cPLA(2)alpha at Ser(505).
      Transfection of a S505A mutant cPLA(2)alpha showed that phosphorylation at
      Ser(505) is key for enzyme activity and LD formation. cPLA(2)alpha contribution
      to LD biogenesis was not because of the generation of arachidonic acid, nor was
      it related to neutral lipid synthesis. cPLA(2)alpha inhibition in cells induced
      to form LD resulted in the appearance of tubulo-vesicular profiles of the smooth
      endoplasmic reticulum, compatible with a role of cPLA(2)alpha in the formation of
      nascent LD from the endoplasmic reticulum.

PMID- 18632669
TI  - Silencing mediator for retinoid and thyroid hormone receptor and nuclear receptor
      corepressor attenuate transcriptional activation by the beta-catenin-TCF4
      complex.
AB  - beta-Catenin is a multifunctional mediator of cellular signaling and an oncogene.
      Nuclear beta-catenin, when complexed with members of the T-cell factor
      (TCF)/leukocyte enhancer factor family of DNA-binding proteins, mediates
      transcriptional activation important for embryonic development and adult cell
      homeostasis. Deregulation of intracellular levels of beta-catenin is an early
      event in the development of a variety of cancers. We observed that the proteins
      silencing mediator for retinoid and thyroid hormone receptor (SMRT) and the
      nuclear receptor corepressor (NCoR) are negative regulators of transcription
      induced by the beta-catenin-TCF4 complex. Overexpression of SMRT and NCoR
      attenuated the transcription of beta-catenin-TCF4-specific reporter gene and of
      CCND1, an endogenous beta-catenin target gene. Knockdown of endogenous SMRT or
      NCoR by short interfering RNA augmented the beta-catenin-TCF4-mediated reporter
      gene expression. Glutathione S-transferase pulldown experiments showed there was
      a direct physical association of SMRT and NCoR with both beta-catenin and TCF4.
      DNA-protein interaction studies revealed that the interactions between either
      SMRT or NCoR and beta-catenin or TCF4 occurred at the promoter regions of CCND1
      and other target genes. These findings demonstrate an important role for
      corepressors SMRT and NCoR in the regulation of beta-catenin-TCF4-mediated gene
      transcription.

PMID- 18632670
TI  - Heat shock transcription factor 1-activating compounds suppress polyglutamine
      induced neurodegeneration through induction of multiple molecular chaperones.
AB  - Many neurodegenerative diseases including Alzheimer, Parkinson, and polyglutamine
      (polyQ) diseases are thought to be caused by protein misfolding. The polyQ
      diseases, including Huntington disease and spinocerebellar ataxias (SCAs), are
      caused by abnormal expansions of the polyQ stretch in disease-causing proteins,
      which trigger misfolding of these proteins, resulting in their deposition as
      inclusion bodies in affected neurons. Although genetic expression of molecular
      chaperones has been shown to suppress polyQ protein misfolding and
      neurodegeneration, toward developing a therapy, it is ideal to induce endogenous
      molecular chaperones by chemical administration. In this study, we assessed the
      therapeutic effects of heat shock transcription factor 1 (HSF1)-activating
      compounds, which induce multiple molecular chaperones, on polyQ-induced
      neurodegeneration in vivo. We found that oral administration of 17-(allylamino)
      17-demethoxygeldanamycin (17-AAG) markedly suppresses compound eye degeneration
      and inclusion body formation in a Drosophila model of SCA. 17-AAG also
      dramatically rescued the lethality of the SCA model (74.1% rescue) and suppressed
      neurodegeneration in a Huntington disease model (46.3% rescue), indicating that
      17-AAG is widely effective against various polyQ diseases. 17-AAG induced Hsp70,
      Hsp40, and Hsp90 expression in a dose-dependent manner, and the expression levels
      correlated with its therapeutic effects. Furthermore, knockdown of HSF1 abolished
      the induction of molecular chaperones and the therapeutic effect of 17-AAG,
      indicating that its therapeutic effects depend on HSF1 activation. Our study
      indicates that induction of multiple molecular chaperones by 17-AAG treatment is
      a promising therapeutic approach for a wide range of polyQ diseases and possibly
      other neurodegenerative diseases.

PMID- 18632671
TI  - Providing information for patients.

PMID- 18632675
TI  - Roche is suspended from ABPI for "actions likely to bring discredit" on the
      industry.

PMID- 18632672
TI  - Interventions before consultations to help patients address their information
      needs by encouraging question asking: systematic review.
AB  - OBJECTIVE: To assess the effects on patients, clinicians, and the healthcare
      system of interventions before consultations to help patients or their
      representatives gather information in consultations by question asking. DESIGN:
      Systematic review with meta-analysis. DATA SOURCES: Electronic literature
      searches of seven databases and hand searching of one journal and bibliographies
      of relevant articles. Review methods Inclusion criteria included randomised
      controlled trials. MAIN OUTCOME MEASURES: Primary outcomes were question asking;
      patients' anxiety, knowledge, and satisfaction; and length of consultation.
      RESULTS: 33 randomised trials of variable quality involving 8244 patients were
      identified. A few studies showed positive effects. Meta-analyses showed small and
      statistically significantly increases in question asking (standardised mean
      difference 0.27, 95% confidence interval 0.19 to 0.36) and patients' satisfaction
      (0.09, 0.03 to 0.16). Non-statistically significant changes occurred in patients'
      anxiety before consultations (weighted mean difference -1.56, -7.10 to 3.97),
      patients' anxiety after consultations (standardised mean difference -0.08, -0.22
      to 0.06), patients' knowledge (-0.34, -0.94 to 0.25), and length of consultation
      (0.10, -0.05 to 0.25). Interventions comprising written materials had similar
      effects on question asking, consultation length, and patients' satisfaction as
      those comprising the coaching of patients. Interventions with additional training
      of clinicians had little further effect than those targeted at patients alone for
      patients' satisfaction and consultation length. CONCLUSIONS: Interventions for
      patients before consultations produce small benefits for patients. This may be
      because patients and clinicians have established behaviours in consultations that
      are difficult to change. Alternatively small increases in question asking may not
      be sufficient to make notable changes to other outcomes.

PMID- 18632676
TI  - Young people carry a disproportionate burden of sexually transmitted infections
      in UK.

PMID- 18632677
TI  - Slow progress in tackling alcohol misuse and obesity risks derailing other health
      gains.

PMID- 18632678
TI  - Should we treat subclinical hypothyroidism?

PMID- 18632679
TI  - Confronting therapeutic ignorance.

PMID- 18632680
TI  - Chief medical officer outlines how more data collection can make surgery safer.

PMID- 18632681
TI  - Judge tries to broker treatment deal for patients with macular degeneration in
      funding row.

PMID- 18632682
TI  - Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical
      Wnt signaling.
AB  - Polycystin-1 (PC1), the product of the PKD1 gene mutated in the majority of
      autosomal dominant polycystic kidney disease (ADPKD) cases, undergoes a cleavage
      resulting in the intracellular release of its C-terminal tail (CTT). Here, we
      demonstrate that the PC1 CTT co-localizes with and binds to beta-catenin in the
      nucleus. This interaction requires a nuclear localization motif present in the
      PC1 CTT as well as the N-terminal portion of beta-catenin. The PC1 CTT inhibits
      the ability of both beta-catenin and Wnt ligands to activate T-cell factor (TCF)
      dependent gene transcription, a major effector of the canonical Wnt signaling
      pathway. The PC1 CTT may produce this effect by reducing the apparent affinity of
      the interaction between beta-catenin and the TCF protein. DNA microarray analysis
      reveals that the canonical Wnt signaling pathway is activated in ADPKD patient
      cysts. Our results suggest a novel mechanism through which PC1 cleavage may
      impact upon Wnt-dependent signaling and thereby modulate both developmental
      processes and cystogenesis.

PMID- 18632684
TI  - Somatic microindels in human cancer: the insertions are highly error-prone and
      derive from nearby but not adjacent sense and antisense templates.
AB  - Somatic microindels (microdeletions with microinsertions) have been studied in
      normal mouse tissues using the Big Blue lacI transgenic mutation detection
      system. Here we analyze microindels in human cancers using an endogenous and
      transcribed gene, the TP53 gene. Microindel frequency, the enhancement of 1-2
      microindels and other features are generally similar to that observed in the non
      transcribed lacI gene in normal mouse tissues. The current larger sample of
      somatic microindels reveals recurroids: mutations in which deletions are
      identical and the co-localized insertion is similar. The data reveal that the
      inserted sequences derive from nearby but not adjacent sequences in contrast to
      the slippage that characterizes the great majority of pure microinsertions. The
      microindel inserted sequences derive from a template on the sense or antisense
      strand with similar frequency. The estimated error rate of the insertion process
      of 13% per bp is by far the largest reported in vivo, with the possible exception
      of somatic hypermutation in the immunoglobulin gene. The data constrain possible
      mechanisms of microindels and raise the question of whether microindels are
      'scars' from the bypass of large DNA adducts by a translesional polymerase, e.g.
      the 'Tarzan model' presented herein.

PMID- 18632685
TI  - A large deletion in the human alpha-globin cluster caused by a replication error
      is associated with an unexpectedly mild phenotype.
AB  - We have characterized a newly identified 16.6 kb deletion which removes a
      significant proportion of the human alpha-globin cluster including the psizeta1,
      alpha(D), psialpha1 and alpha2-globin genes but leaves the duplicated alpha1 gene
      intact. This complicated rearrangement results from a combination of slippage and
      strand switching at sites of microhomology during replication. Functional
      analysis shows that expression of the remaining alpha1 gene is increased, rather
      than down-regulated by this deletion. This could be related to its proximity to
      the remote upstream alpha-globin regulatory elements or reduced competition for
      these elements in the absence of the dominant alpha2-globin gene. The finding of
      a very mild phenotype associated with such an extensive deletion in the alpha
      globin cluster implies that much of the DNA removed by the deletion is likely to
      be functionally unimportant. These findings suggest that other than the upstream
      regulatory elements and promoter proximal elements there are unlikely to be
      additional positive cis-acting sequences in the alpha-globin cluster.

PMID- 18632683
TI  - A set of differentially expressed miRNAs, including miR-30a-5p, act as post
      transcriptional inhibitors of BDNF in prefrontal cortex.
AB  - Expression of brain-derived neurotrophic factor (BDNF) is developmentally
      regulated in prefrontal cortex (PFC). The underlying molecular mechanisms,
      however, remain unclear. Here, we explore the role of microRNAs (miRNAs) as post
      transcriptional inhibitors of BDNF. A sequential approach involving in silico,
      miRNA microarray, in situ hybridization and qRT-PCR studies identified a group of
      10 candidate miRNAs, segregating into five miRNA families (miR-30a-5p/b/c/d, miR
      103/107, miR-191, miR-16/195, miR-495), which exhibited distinct developmental
      and lamina-specific expression in human PFC. Luciferase assays confirmed that at
      least two of these miRNAs, miR-30a-5p and miR-195, target specific sequences
      surrounding the proximal polyadenylation site within BDNF 3'-untranslated region.
      Furthermore, neuronal overexpression of miR-30a-5p, a miRNA enriched in layer III
      pyramidal neurons, resulted in down-regulation of BDNF protein. Notably, a subset
      of seven miRNAs, including miR-30a-5p, exhibited an inverse correlation with BDNF
      protein levels in PFC of subjects age 15-84 years. In contrast, the role of
      transcriptional mechanisms was more apparent during the transition from fetal to
      childhood and/or young adult stages, when BDNF mRNA up-regulation was accompanied
      by similar changes in (open chromatin-associated) histone H3-lysine 4 methylation
      at BDNF gene promoters I and IV. Collectively, our data highlight the multiple
      layers of regulation governing the developmental expression of BDNF in human PFC
      and suggest that miRNAs are involved in the fine-tuning of this neurotrophin
      particularly in adulthood.

PMID- 18632686
TI  - Harlequin ichthyosis model mouse reveals alveolar collapse and severe fetal skin
      barrier defects.
AB  - Harlequin ichthyosis (HI), which is the most severe genodermatosis, is caused by
      loss-of-function mutations in ABCA12, a member of the ATP-binding cassette
      transporter family. To investigate the pathomechanism of HI and the function of
      the ABCA12 protein, we generated ABCA12-deficient mice (Abca12(-/-)) by targeting
      Abca12. Abca12(-/-) mice closely reproduce the human HI phenotype, showing marked
      hyperkeratosis with eclabium and skin fissure. Lamellar granule abnormalities and
      defective ceramide distribution were remarkable in the epidermis. Skin
      permeability assay of Abca12(-/-) fetuses revealed severe skin barrier
      dysfunction after the initiation of keratinization. Surprisingly, the Abca12(-/-)
      mice also demonstrated lung alveolar collapse immediately after birth. Lamellar
      bodies in alveolar type II cells of the Abca12(-/-) mice lacked normal lamellar
      structures. The level of surfactant protein B, an essential component of alveolar
      surfactant, was reduced in the Abca12(-/-) mice. Fetal therapeutic trials with
      systemic administration of retinoid or dexamethasone, which are effective for HI
      and respiratory distress, respectively, to the pregnant mother mice neither
      improved the skin phenotype nor extended the survival period. Our HI model mice
      reproduce the human HI skin phenotype soon after the initiation of fetal skin
      keratinization and provide evidence that ABCA12 plays pivotal roles in lung and
      skin barrier functions.

PMID- 18632689
TI  - Stems cells and regeneration: special review issue.

PMID- 18632690
TI  - Aneuploidy and early human embryo development.
AB  - Human embryo development occurs through a process that encompasses reprogramming,
      sequential cleavage divisions and mitotic chromosome segregation and embryonic
      genome activation. Chromosomal abnormalities may arise during germ cell and/or
      pre-implantation embryo development, and are a major cause of spontaneous
      miscarriage or birth defects. Nonetheless, model systems suitable for the study
      of human germ cell and embryo development have been limited until recently. We
      suggest that human embryonic stem cells may provide a valuable human cell-based
      model for genetic studies of human pre-implantation pluripotent cells. Here, we
      review the current literature on diagnosing chromosomal abnormalities in the pre
      implantation embryo, and the importance of provisions from the human oocyte in
      establishing and maintaining the human embryonic genome during the first 3 days
      post-conception. We focus on transcriptional analysis of human oocytes and
      embryos and the unique cell cycle and checkpoint requirements in the early
      embryo. Taken together, data suggest that the unique programs of the early human
      embryo, including management of aneuploid cells, may paradoxically promote embryo
      development but contribute to the high rate of spontaneous miscarriages in human
      pregnancies.

PMID- 18632687
TI  - TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress
      granules.
AB  - Our previous work has demonstrated that the Tudor domain of the 'survival of
      motor neuron' protein and the Tudor domain-containing protein 3 (TDRD3) are
      highly similar and that they both have the ability to interact with arginine
      methylated polypeptides. TDRD3 has been identified among genes whose
      overexpression has a strong predictive value for poor prognosis of estrogen
      receptor-negative breast cancers, although its precise function remains unknown.
      TDRD3 is a modular protein, and in addition to its Tudor domain, it harbors a
      putative nucleic acid recognition motif and a ubiquitin-associated domain. We
      report here that TDRD3 localizes predominantly to the cytoplasm, where it co
      sediments with the fragile X mental retardation protein on actively translating
      polyribosomes. We also demonstrate that TDRD3 accumulates into stress granules
      (SGs) in response to various cellular stresses. Strikingly, the Tudor domain of
      TDRD3 was found to be both required and sufficient for its recruitment to SGs,
      and the methyl-binding surface in the Tudor domain is important for this process.
      Pull down experiments identified five novel TDRD3 interacting partners, most of
      which are potentially methylated RNA-binding proteins. Our findings revealed that
      two of these proteins, SERPINE1 mRNA-binding protein 1 and DEAD/H box-3 (a gene
      often deleted in Sertoli-cell-only syndrome), are also novel constituents of
      cytoplasmic SGs. Taken together, we report the first characterization of TDRD3
      and its functional interaction with at least two proteins implicated in human
      genetic diseases and present evidence supporting a role for arginine methylation
      in the regulation of SG dynamics.

PMID- 18632688
TI  - Neocortical expression of mutant huntingtin is not required for alterations in
      striatal gene expression or motor dysfunction in a transgenic mouse.
AB  - Huntington's disease (HD) is an autosomal-dominant neurodegenerative disease
      caused by an expanded polyglutamine tract in the ubiquitously expressed
      huntingtin protein. Clinically, HD is characterized by motor, cognitive and
      psychiatric deficits. Striking degeneration of the striatum is observed in HD
      with the medium spiny neurons (MSNs) being the most severely affected neuronal
      subtype. Dysfunction of MSNs is marked by characteristic changes in gene
      expression which precede neuronal death. The ubiquitous expression of the
      huntingtin protein raises the question as to whether the selective vulnerability
      of the MSN is cell-autonomous, non-cell-autonomous, or a combination thereof. In
      particular, growing evidence suggests that abnormalities of the cortex and
      corticostriatal projections may be primary causes of striatal vulnerability. To
      examine this issue, we developed transgenic mice that, within the forebrain,
      selectively express a pathogenic huntingtin species in the MSNs, specifically
      excluding the neocortex. These mice develop a number of abnormalities
      characteristic of pan-cellular HD mouse models, including intranuclear inclusion
      bodies, motor impairment, and changes in striatal gene expression. As this
      phenotype develops in the presence of normal levels of brain-derived neurotrophic
      factor and its major striatal receptor, tropomyosin-related kinase B, these data
      represent the first demonstration of in vivo cell-autonomous transcriptional
      dysregulation in an HD mouse model. Furthermore, our findings suggest that
      therapies targeted directly to the striatum may be efficacious at reversing some
      of the molecular abnormalities present in HD.

PMID- 18632691
TI  - Seminal discoveries in regenerative medicine: contributions of the male germ line
      to understanding pluripotency.
AB  - Germ cells are highly specialized cells that form gametes (sperm and eggs), and
      they are the only cells within an organism that contribute genes to offspring.
      Due to the fact that the genetic information contained within germ cells is
      passed from generation to generation, the germ line is often thought of as
      immortal. Studies have revealed that germ cells are remarkably similar to
      pluripotent embryonic stem cells (ESCs). For example, there is a significant
      overlap in the gene expression profile between ESCs and primordial germ cells
      (PGCs), the founders of the germ cell lineage. In addition, pluripotent embryonic
      germ (EG) cell lines have been derived from mammalian PGCs. Secondly, a subset of
      testicular germ cell tumors, known as non-seminomas, often contain differentiated
      cells representative of all three germ layers, a definitive test of pluripotency.
      Lastly, recent results have demonstrated the ability of spermatogonial stem cells
      (SSCs) to de-differentiate into pluripotent ES-like cells, underscoring a unique
      relationship between the germ line and pluripotent cells that are present during
      the earliest stages of embryonic development. Here, we will review the factors
      that regulate the self-renewal and maintenance of male germline stem cells (GSCs)
      and discuss how these factors may allow us to manipulate the germ line to create
      pluripotent cells that could serve as a critical tool in cell replacement
      therapies and regenerative medicine.

PMID- 18632692
TI  - Molecular basis of pluripotency.
AB  - Embryonic stem (ES) cells are pluripotent and capable of self-renewal, thus
      holding promise for regenerative medicine. Recent studies have begun to provide
      insights into the molecular mechanisms underlying pluripotency and self-renewal.
      In this article, we discuss the roles of transcriptional regulation, epigenetic
      regulation and miRNAs in the maintenance of pluripotency and the differentiation
      of ES cells.

PMID- 18632693
TI  - Epigenetic regulation of stem cell fate.
AB  - Stem cell-based regenerative medicine holds great promise for repair of diseased
      tissue. Modern directions in the field of epigenetic research aimed to decipher
      the epigenetic signals that give stem cells their unique ability to self-renew
      and differentiate into different cell types. However, this research is only the
      tip of the iceberg when it comes to writing an 'epigenetic instruction manual'
      for the ramification of molecular details of cell commitment and differentiation.
      In this review, we discuss the impact of the epigenetic research on our
      understanding of stem cell biology.

PMID- 18632694
TI  - The road to pluripotence: the research response to the embryonic stem cell
      debate.
AB  - The controversies surrounding embryonic stem cell research have prompted
      scientists to invent beyond restrictive national policy and moral concerns. The
      impetus behind these reports comes from different sources, including individually
      held moral beliefs, societal pressures and resource constraints, both biological
      and financial. Along with other contributions to public policy such as advocacy
      or public testimony, experimentation and scientific curiosity are perhaps more
      natural responses scientists use to surmount impediments to research. In a
      research context, we review the history of the first stem cell discoveries, and
      describe scientific efforts leading up to recent reports of pluripotent lines
      made without the use of human embryos and eggs. We argue that despite the promise
      of these new lines, we must not lose sight of fundamental questions remaining at
      the frontiers of embryology and early human development. The answers to these
      questions will impact studies of genetics, cell biology and diseases such as
      cancer, autoimmunity and disorders of development. Human embryonic stem cell
      research is barely a decade old. The recent pace of discovery--in spite of
      federal restrictions--is testament to the potential of these cells to uncover
      some of biology's most intractable mysteries.

PMID- 18632695
TI  - Generation of isogenic pluripotent stem cells.
AB  - The ability to reprogram somatic cell nuclei back into a pluripotent epigenetic
      state provides exciting new possibilities for in vitro research and cell
      transplantation therapy. There has been a significant quantity of recent research
      studies demonstrating that this epigenetic reprogramming process is possible with
      human and non-human primate somatic cells. In this review, various methodologies
      for reprogramming primate somatic cells into pluripotent stem cells are examined,
      epigenetic reprogramming following somatic cell nuclear transfer and normal
      primate embryonic development is compared, and future potential methods to induce
      direct reprogramming without using genetic modification are discussed.

PMID- 18632696
TI  - Canine embryo-derived stem cells and models for human diseases.
AB  - Embryonic stem (ES) cells are pluripotent and permanent cell lines which can
      differentiate into cell types of all the three germ layers. These features imply
      multiple opportunities for clinical applications in tissue engineering and
      regenerative medicine. Most of our knowledge on the biology and technology of ES
      cells is derived from studies with mouse ES cells. While appropriate for proof-of
      principle studies, the mouse model has limitations in its application in
      translational, pre-clinical studies. This is particularly true for studies
      evaluating the safety and efficacy of stem cell therapies. For this purpose,
      large animal models more closely mimicking important aspects of human anatomy,
      physiology and pathology than mouse models are urgently needed. In this context,
      the dog is an excellent candidate: the plethora of different dog breeds offer a
      large phenotypic and genetic variability, which can be exploited increasingly
      well due to the advanced status of the dog genome project and the rapidly growing
      box of genomic tools. Recently, the first pluripotent canine embryo-derived stem
      cells have been described, further increasing the potential of the dog as a model
      system for regenerative medicine. Although these cells express alkaline
      phosphatase, NANOG and OCT4, and can be differentiated in vitro towards endoderm
      , mesoderm- and ectoderm-lineages (typical features of human and mouse ES cells),
      their in vivo differentiation capability, i.e. formation of teratomas in
      immunodeficient mice or contribution to chimeric animals, remains to be
      demonstrated. Here, we discuss the features of reported canine embryo-derived
      cells and their potential applications in basic and translational biomedical
      research.

PMID- 18632697
TI  - Good manufacturing practice and clinical-grade human embryonic stem cell lines.
AB  - Human embryonic stem cell (hESC) lines, after directed differentiation, hold the
      greatest potential for cell transplantation treatment in many severe diseases.
      Good manufacturing practice (GMP) quality, defined by both the European Medicines
      Agency and the Food and Drug Administration, is a requirement for clinical-grade
      cells, offering optimal defined quality and safety in cell transplantation. Using
      animal substance-free culture media, feeder cells or feeder-free matrix in
      derivation, passaging, expansion and cryopreservation procedures, immune
      reactions against animal proteins in the cells, and infection risk caused by
      animal microbes can be avoided. It is also possible to apply GMP to animal
      components if no better options are available. In recent production of GMP
      quality hESC lines, feeder cells had been cultured in fetal bovine serum, and the
      medium supplemented with an animal protein containing a serum replacement
      component. Using embryos cultured in a GMP laboratory, isolating the inner cell
      mass mechanically, deriving lines on human feeder cells originally cultured in
      xeno-free medium in a GMP laboratory, and using xeno-free media for derivation
      and culture of hESC lines themselves, GMP-quality xeno-free hESC lines could be
      established today. Human serum is a xeno-free component available today, but many
      chemically defined media are under development.

PMID- 18632698
TI  - Skin and hair: models for exploring organ regeneration.
AB  - Skin is an excellent model to study the basic biology of organ regeneration and
      translational approaches to regenerative medicine. Because of the accessibility
      of the skin, a long history of regenerative approaches already exists.
      Identifying the commonalities between skin regeneration and the regeneration of
      other organs could provide major breakthroughs in regenerative medicine. The hair
      follicle represents a miniature organ with readily accessible stem cells,
      multiple cell lineages, and signaling centers. During the normal lifespan of a
      human, this miniature organ regenerates itself more than 10 times. The cells
      responsible for this remarkable process are called bulge stem cells. A plethora
      of molecular and genetic tools have been developed to follow their fate and to
      explore their ontogeny. Major advances have been made toward understanding the
      normal cell fate of bulge stem cells and their developmental plasticity. Recent
      studies suggest the epidermis and hair may have an untapped potential to form
      other organs. Understanding the mechanisms that regulate adult stem-cell
      proliferation is a major goal for regenerative medicine. In the hair follicle,
      pharmacologic agents, recombinant proteins, and artificial cell-permeable
      proteins have been developed to manipulate the proliferation of the quiescent
      bulge stem cells. These advances illustrate a potential roadmap for regenerative
      medicine using molecular tools developed for skin biology to promote organ
      regeneration by manipulating adult stem cells in situ.

PMID- 18632699
TI  - Neur-ons and neur-offs: regulators of neural induction in vertebrate embryos and
      embryonic stem cells.
AB  - Although the spatial and temporal orchestration of early vertebrate embryogenesis
      is missing from cell culture systems, recent work suggests that many of the same
      signals affecting neural induction in vertebrate embryos also regulate embryonic
      stem (ES) cell neurogenesis. One key regulatory mechanism involved in both in
      vivo and in vitro neural induction is the inhibition of bone morphogenetic
      protein (BMP) signals. Wnts and Fibroblast Growth Factors represent additional
      regulatory influences, which may affect the adoption of neural fates through both
      BMP-dependent and BMP-independent mechanisms. Insights into neural induction in
      vivo help to guide paradigms for promoting neural differentiation by ES cells.
      Conversely, insights into the mechanisms by which ES cells adopt neural fates may
      provide an improved understanding of neural induction in the early embryo.

PMID- 18632700
TI  - Multiple layers of molecular controls modulate self-renewal and neuronal lineage
      specification of embryonic stem cells.
AB  - Elucidating the molecular changes that arise during neural differentiation and
      fate specification is crucial for building accurate in vitro models of
      neurodegenerative diseases using human embryonic stem cells (hESCs). Here we
      review the importance of hESCs and derived progenitors in treating and modeling
      neurological diseases, and summarize the current efforts for the differentiation
      of hESCs into neural progenitors and defined neurons. We recapitulate the recent
      findings and discuss open questions on aspects of molecular control of gene
      expression by chromatin modification and methylation, posttranscriptional
      regulation by alternative splicing and the action of microRNAs, and protein
      modification. An integrative view of the different levels will hopefully provide
      much needed insight into understanding stem cell biology.

PMID- 18632701
TI  - Stem cell-based strategies for treating pediatric disorders of myelin.
AB  - The pediatric leukodystrophies comprise a category of disease manifested by
      neonatal or childhood deficiencies in myelin production or maintenance; these may
      be due to hereditary defects in one or more genes critical to the initiation of
      myelination, as in Pelizaeus-Merzbacher Disease, or to enzymatic deficiencies
      with aberrant substrate accumulation-related dysfunction, as in the lysosomal
      storage disorders. Despite differences in both phenotype and natural history,
      these disorders are all essentially manifested by a profound deterioration in
      neurological function with age. A congenital deficit in forebrain myelination is
      also noted in children with the periventricular leukomalacia of cerebral palsy,
      another major source of neurological morbidity. In light of the wide range of
      disorders to which congenital hypomyelination and/or postnatal demyelination may
      contribute, and the relative homogeneity of central oligodendrocytes and their
      progenitors, the pediatric leukodystrophies may be especially attractive targets
      for cell-based therapeutic strategies. As a result, glial progenitor cells
      (GPCs), which can give rise to new myelinogenic oligodendrocytes, have become of
      great interest as potential therapeutic vectors for the restoration of myelin to
      the hypomyelinated or dysmyelinated childhood CNS. In addition, by distributing
      themselves throughout the deficient host neuraxis after perinatal allograft, and
      giving rise to astrocytes as well as oligodendrocytes, glial progenitors appear
      to be of potential great utility in rectifying enzymatic deficiencies. In this
      review, we focus on current efforts to develop the use of isolated human GPCs as
      transplantable agents both for mediating enzymatic restoration to the enzyme
      deficient brain and for therapeutic myelination in the disorders of congenital
      hypomyelination.

PMID- 18632702
TI  - Cellular repair of CNS disorders: an immunological perspective.
AB  - Cellular repair is a promising strategy for treating central nervous system (CNS)
      disorders. Several strategies have been contemplated including replacement of
      neurons or glia that have been lost due to injury or disease, use of cellular
      grafts to modify or augment the functions of remaining neurons and/or use of
      cellular grafts to protect neural tissue by local delivery of growth or trophic
      factors. Depending on the specific disease target, there may be one or many cell
      types that could be considered for therapy. In each case, an additional variable
      must be considered--the role of the immune system in both the injury process
      itself and in the response to incoming cells. Cellular transplants can be roughly
      categorized into autografts, allografts and xenografts. Despite the immunological
      privilege of the CNS, allografts and xenografts can elicit activation of the
      innate and adaptive immune system. In this article, we evaluate the various
      effects that immune cells and signals may have on the survival, proliferation,
      differentiation and migration/integration of transplanted cells in therapeutic
      approaches to CNS injury and disease.

PMID- 18632703
TI  - Cell-based therapies for skeletal regenerative medicine.
AB  - Skeletal deficits represent a substantial biomedical burden on the US healthcare
      system. Current strategies for reconstructing bony defects are fraught with
      inadequacies. Cell-based therapies for skeletal regeneration offer a paradigm
      shift that may provide alternative solutions. Substantial work has identified a
      host of cellular sources that possess the potential for osteogenic
      differentiation. Significant efforts have been devoted toward characterizing the
      role of postnatal cellular sources that are relatively abundant and easily
      accessible. Among these, the potential of using adipose-derived stromal cells for
      skeletal regeneration has garnered much interest. Integral to these efforts
      directed at characterizing cellular sources are studies that seek to understand
      the factors that initiate and regulate osteogenic differentiation of progenitor
      cells. Specifically, focus has been directed on elucidating the role of bone
      morphogenetic protein and fibroblast growth factor signaling in regulating
      osteogenic differentiation of osteoprogenitor cells. Concurrent studies in the
      field of scaffold design have also helped to advance the potential for cell-based
      therapies.

PMID- 18632705
TI  - Dietary iron and blood pressure.

PMID- 18632704
TI  - Relation of iron and red meat intake to blood pressure: cross sectional
      epidemiological study.
AB  - OBJECTIVE: To investigate associations of dietary iron (total, haem, and non
      haem), supplemental iron, and red meat with blood pressure. DESIGN: Cross
      sectional epidemiological study. SETTING: 17 population samples from Japan,
      China, the United Kingdom, and the United States participating in the
      international collaborative study on macro-/micronutrients and blood pressure
      (INTERMAP). PARTICIPANTS: 4680 adults aged 40-59. MAIN OUTCOME MEASURE: Average
      of eight blood pressure readings. RESULTS: In multiple linear regression analyses
      dietary total iron and non-haem iron were consistently inversely associated with
      blood pressure. With adjustment for potential non-dietary and dietary
      confounders, dietary total iron intake higher by 4.20 mg/4.2 MJ (2 SD) was
      associated with -1.39 mm Hg (P<0.01) lower systolic blood pressure. Dietary non
      haem iron intake higher by 4.13 mg/4.2 MJ (2 SD) was associated with -1.45 mm Hg
      (P<0.001) lower systolic blood pressure. Differences were smaller for diastolic
      blood pressure. In most models haem iron intake from food was positively, non
      significantly associated with blood pressure. Iron intake from combined diet and
      supplements yielded smaller associations than dietary iron alone. Red meat intake
      was directly associated with blood pressure; 102.6 g/24 h (2 SD) higher intake
      was associated with 1.25 mm Hg higher systolic blood pressure. Associations
      between red meat and blood pressure persisted after adjustment for multiple
      confounders. CONCLUSION: Non-haem iron has a possible role in the prevention and
      control of adverse blood pressure levels. An unfavourable effect of red meat on
      blood pressure was observed. These results need confirmation including in
      prospective studies, clinical trials, and from experimental evidence on possible
      mechanisms.

PMID- 18632706
TI  - High tech gadgetry introduced by stealth.

PMID- 18632707
TI  - How it really works.

PMID- 18632708
TI  - Key opinion leaders: Thus are our medical meetings managed.

PMID- 18632709
TI  - Key opinion leaders: How to spot one.

PMID- 18632710
TI  - Key opinion leaders: Getting them while they're young.

PMID- 18632711
TI  - General practitioners must have their own list.

PMID- 18632712
TI  - A friend in need: Caring still lives.

PMID- 18632713
TI  - US paediatricians and cardiologists are criticised for recommending statins for
      children.

PMID- 18632714
TI  - FDA adds "black box" warning label to fluoroquinolone antibiotics.

PMID- 18632715
TI  - Consensus emerges on need for US agency similar to NICE.

PMID- 18632716
TI  - European Commission plans free fruit and vegetable scheme in schools.

PMID- 18632717
TI  - Manners in medicine: What's in a name?

PMID- 18632718
TI  - Complementary medicine: Regulating the irregular is a contradiction.

PMID- 18632719
TI  - Antipsychotics for dementia is metaphor for elderly care.

PMID- 18632720
TI  - The future of primary and community care in England.

PMID- 18632721
TI  - Prevalence of undertreatment in cancer pain. A review of published literature.
AB  - BACKGROUND: Pain is a major health care problem for patients with cancer: despite
      the existence of guidelines for cancer pain management, undertreatment is a
      widespread problem. Pain Management Indexes (PMIs) evaluate the congruence
      between the patient's reported level of pain and the intensity/strength of the
      analgesic therapy. Negative scores indicate inadequate prescriptions. MATERIALS
      AND METHODS: We conducted a Medline search using terms for 'pain management',
      'index' or 'measure' to select studies which measured undertreatment in cancer
      settings. Univariate and multivariate logistic regression identified associations
      between independent predictors and high prevalence of undertreatment. RESULTS:
      Among the 44 studies identified, 26 studies used the PMI as proposed by Cleeland.
      The range of negative PMI varied from 8% to 82% with a weighted mean value of
      43%. In multivariate analyses, factors associated with negative PMI were date of
      publication before 2001, provenance from Europe or Asia and countries with a
      gross national income per capita < $40,000 per year and a care setting not
      specific for cancer. Age was not a significant predictor for undertreatment.
      CONCLUSION: Nearly one of two patients with cancer pain is undertreated. The
      percentage is high, but consists of a large variability of undertreatment across
      studies and settings.

PMID- 18632722
TI  - Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal
      cancer.
AB  - BACKGROUND: In advanced colorectal cancer, K-Ras somatic mutations predict
      resistance to mAbs targeting epidermal growth factor receptor (EGFR).
      Relationships between K-Ras mutations and EGFR status have not been examined so
      far. We analyzed relationships between K-Ras mutations and EGFR tumoral status
      based on EGFR germinal polymorphisms, gene copy number and expression. METHODS:
      Eighty colorectal tumors (stage 0-IV) and 39 normal mucosas were analyzed. K-Ras
      mutations at codons 12 and 13 were detected by a sensitive enrichment double PCR
      restriction fragment length polymorphism (RFLP) assay. EGFR gene polymorphisms at
      positions -216G>T, -191C>A and 497Arg>Lys were analyzed (PCR-RFLP), along with CA
      repeat polymorphism in intron 1 (fluorescent genotyping) and EGFR gene copy
      number (PCR amplification). EGFR expression was quantified by Scatchard binding
      assay. RESULTS: The number of EGFR high-affinity sites, dissociation constant
      (Kd), gene copy number, intron 1, -216G>T, -191C>A or 497Lys>Arg genotypes was
      not different between K-Ras-mutated or K-Ras-non-mutated tumors. No relationship
      was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR
      expression was not related to gene copy number. EGFR gene copy number in tumor
      and normal tissue was not correlated. The mean value of the tumor/normal mucosa
      gene copy number ratio was 1.16. CONCLUSIONS: Present data clearly show that EGFR
      status is independent of K-Ras mutations in colorectal tumors.

PMID- 18632724
TI  - Association of the polymorphism of the CAG repeat in the mitochondrial DNA
      polymerase gamma gene (POLG) with testicular germ-cell cancer.
AB  - BACKGROUND: A possible association between the polymorphic CAG repeat in the DNA
      polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT)
      was investigated in this study. The hypothesis was prompted by an earlier
      preliminary study proposing an association of the absence of the common 10-CAG
      long POLG allele with testicular cancer as well as previously reported in some
      European populations' association with male subfertility, which is a condition
      carrying an increased risk of TGCT. PATIENTS AND METHODS: The number of CAG
      repeats in both POLG alleles was established in 243 patients with TGCT and in 869
      controls by the analysis of the genomic DNA fragment. RESULTS: A significantly
      higher proportion of men homozygous allele of other than the common 10 CAG
      repeats was found among the patients with TGCT in comparison to the controls
      (4.9% versus 1.3%, respectively, P = 0.001). The vast majority of the homozygous
      patients had a seminoma (11 of 12; 97%), despite that only about half (55%) of
      the studied patients had this tumour type. CONCLUSIONS: The findings indicate
      that the POLG polymorphism may be a contributing factor in the pathogenesis of
      TGCT particularly in seminoma, but the mechanisms remain to be elucidated.

PMID- 18632723
TI  - Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small
      cell lung cancer: a phase II study.
AB  - BACKGROUND: The purpose of this study was to evaluate the potential of
      noncytotoxic doses of suramin to reverse chemotherapy resistance in advanced
      chemonaive and chemoresistant non-small-cell lung cancer patients. PATIENTS AND
      METHODS: Patients received paclitaxel (Taxol) (200 mg/m(2)) and carboplatin (area
      under the concentration-time curve 6 mg/ml/min) every 3 weeks. The total suramin
      per cycle dose was calculated using a nomogram derived from the preceding phase I
      trial to obtain the desirable plasma concentration range of 10-50 microM.
      RESULTS: Thirty-nine response-assessable chemonaive patients (arm A) received 213
      cycles. Thirty-eight cycles were administered to 15 patients with demonstrated
      resistance to paclitaxel and carboplatin (arm B). The pattern/frequency of toxic
      effects was similar to those expected for paclitaxel/carboplatin, and
      pharmacokinetic analyses (199 cycles) showed suramin plasma concentrations
      maintained between 10 and 50 microM in 94% of cycles. In arm A, response
      evaluation criteria in solid tumors (RECIST) response rate was 36% (95%
      confidence interval 22% to 54%; two complete, 12 partial); 15 patients (38%) had
      disease stabilization for > or =4 months; median progression-free survival
      (intention to treat) was 6.4 months; median overall survival (OS) 10.4 months and
      1-year survival rate 38%. In arm B, no RECIST responses occurred; four patients
      had disease stabilization for > or =4 months; median OS was 132 days and 1-year
      survival rate 7%. Plasma basic fibroblast growth factor levels were higher in
      chemopretreated/refractory patients compared with chemonaive patients (P = 0.05).
      Sequence analysis of the EGFR tyrosine kinase domain in a long-term disease-free
      survivor revealed an ATP-binding pocket mutation (T790M). CONCLUSIONS:
      Noncytotoxic suramin did not increase paclitaxel/carboplatin's toxicity and the
      suramin dose was predicted from clinical parameters. No clinically significant
      reversal of primary resistance was documented, but a modulatory effect in
      chemotherapy-naive patients cannot be excluded. Controlled randomization is
      planned for further evaluation of this treatment strategy.

PMID- 18632725
TI  - Identification of a chemotactic sensitivity in a coupled system.
AB  - Chemotaxis is the process by which cells behave in a way that follows the
      chemical gradient. Applications to bacteria growth, tissue inflammation and
      vascular tumours provide a focus on optimization strategies. Experiments can
      characterize the form of possible chemotactic sensitivities. This paper addresses
      the recovery of the chemotactic sensitivity from these experiments while allowing
      for non-linear dependence of the parameter on the state variables. The existence
      of solutions to the forward problem is analysed. The identification of a
      chemotactic parameter is determined by inverse problem techniques. Tikhonov
      regularization is investigated and appropriate convergence results are obtained.
      Numerical results of concentration-dependent chemotactic terms are explored.

PMID- 18632726
TI  - T cell-derived IL-3 plays key role in parasite infection-induced basophil
      production but is dispensable for in vivo basophil survival.
AB  - Enhanced basophil production is often associated with T(h)2-related conditions
      such as parasite infections or allergic inflammations. Our previous study
      demonstrated that T cell activation is necessary to promote basophil production
      in Nippostrongylus brasiliensis (Nb)-infected mice. Yet, mechanisms underlying
      how T cells aid infection-induced basophil production are not clear. In this
      report, we show that IL-3 produced by T cells activated by the infection enhances
      basophil production in Nb-infected mice. IL-3-deficient mice or Rag2-/-
      recipients of IL-3-deficient T cells but not of wild-type T cells failed to
      support basophil production following the Nb infection. Interestingly, although
      IL-3 was critical for preventing basophil apoptosis in vitro, IL-3 had little
      contribution to basophil survival and proliferation in vivo. Collectively, these
      results highlight a novel mechanism by which activation of adaptive immune
      components induces basophil production but not basophil survival via IL-3
      production.

PMID- 18632727
TI  - Induction of autophagy in porcine kidney cells by quantum dots: a common cellular
      response to nanomaterials?
AB  - Quantum dots (QDs) are being investigated as novel in vivo imaging agents. The
      leaching of toxic metals from these QDs in biological systems is of great
      concern. This study compared the cytotoxic mechanisms of two QD species made of
      different core materials (cadmium selenide [CdSe] vs. indium gallium phosphide
      [InGaP]) but similar core sizes (5.1 vs. 3.7 nm) and surface compositions (both
      ZnS capped, lipid-coated and pegylated). The CdSe QD was found to be 10-fold more
      toxic to porcine renal proximal tubule cells (LLC-PK1) than the InGaP QD on a
      molar basis, as determined by MTT assay (48 h IC(50) 10nM for CdSe vs. 100nM for
      InGaP). Neither of the QD species induced appreciable oxidative stress, as
      determined by lipid peroxide and reduced glutathione content, suggesting that
      toxicity was not metal associated. In agreement, treatment of cells with CdSe QDs
      was not associated with changes in metallothionein-IA (MT-IA) gene expression or
      Cd-associated caspase 3 enzyme activation. By contrast, incubation of the LLC-PK1
      cells with the InGaP QD resulted in a dramatic increase in MT-IA expression by 21
      and 43-fold, at 8 and 24 h, respectively. The most remarkable finding was
      evidence of extensive autophagy in QD-treated cells, as determined by Lysotracker
      Red dye uptake, TEM, and LC3 immunobloting. Autophagy induction has also been
      described for other nanomaterials and may represent a common cellular response.
      These data suggest that QD cytotoxicity is dependent upon properties of the
      particle as a whole, and not exclusively the metal core materials.

PMID- 18632729
TI  - Adaptation of aphid stylectomy for analyses of proteins and mRNAs in barley
      phloem sap.
AB  - Sieve tubes are transport conduits not only for photoassimilates but also for
      macromolecules and other compounds that are involved in sieve tube maintenance
      and systemic signalling. In order to gain sufficient amounts of pure phloem
      exudates from barley plants for analyses of the protein and mRNA composition, a
      previously described stylectomy set-up was optimized. Aphids were placed in
      sealed cages, which, immediately after microcauterization of the stylets, were
      flooded with water-saturated silicon oil. The exuding phloem sap was collected
      with a capillary connected to a pump. Using up to 30 plants and 600 aphids
      (Rhopalosiphum padi) in parallel, an average of 10 mul of phloem sap could be
      obtained within 6 h of sampling. In first analyses of the macromolecular content,
      eight so far unknown phloem mRNAs were identified by cDNA-amplified fragment
      length polymorphism. Transcripts in barley phloem exudates are related to
      metabolism, signalling, and pathogen defence, for example coding for a protein
      kinase and a pathogen- and insect-responsive WIR1A (wheat-induced resistance 1A)
      like protein. Further, one-dimensional gel electrophoresis and subsequent partial
      sequencing by mass spectrometry led to the identification of seven major proteins
      with putative functions in stress responses and transport of mRNAs, proteins, and
      sugars. Two of the discovered proteins probably represent isoforms of a new
      phloem-mobile sucrose transporter. Notably, two-dimensional electrophoresis
      confirmed that there are >250 phloem proteins awaiting identification in future
      studies.

PMID- 18632728
TI  - Emotional memory in schizophrenia.
AB  - Emotional memories play an important role in our day-to-day experience, informing
      many of our minute-to-minute decisions (eg, where to go for dinner, what are the
      likely consequences of not attending a meeting), as well as our long-term goal
      setting. Individuals with schizophrenia appear to be impaired in memory for
      emotional experiences, particularly over longer delay periods, which may
      contribute to deficits in goal-related behavior and symptoms of amotivation and
      anhedonia. This article reviews factors that are known to influence emotional
      memory in healthy subjects, applies these factors to results from emotional
      memory studies with individuals with schizophrenia, and then uses extant
      neurobiological models of emotional memory formation to develop hypotheses about
      biological processes that might particularly contribute to emotional memory
      impairment in schizophrenia.

PMID- 18632730
TI  - Hexameric oligomerization of mitochondrial peroxiredoxin PrxIIF and formation of
      an ultrahigh affinity complex with its electron donor thioredoxin Trx-o.
AB  - Mitochondria from plants, yeast, and animals each contain at least one
      peroxiredoxin (Prx) that is involved in peroxide detoxification and redox
      signalling. The supramolecular dynamics of atypical type II Prx targeted to the
      mitochondrion was addressed in pea. Microcalorimetric (ITC) titrations identified
      an extremely high-affinity binding between the mitochondrial PsPrxIIF and Trx-o
      with a K(D) of 126+/-14 pM. Binding was driven by a favourable enthalpy change
      (DeltaH= -60.6 kcal mol(-1)) which was counterbalanced by unfavourable entropy
      changes (TDeltaS= -47.1 kcal mol(-1)). This is consistent with the occurrence of
      large conformational changes during binding which was abolished upon site
      directed mutaganesis of the catalytic C59S and C84S. The redox-dependent
      interaction was confirmed by gel filtration of mitochondrial extracts and co
      immunoprecipitation from extracts. The heterocomplex of PsPrxIIF and Trx-o
      reduced peroxide substrates more efficiently than free PsPrxIIF suggesting that
      Trx-o serves as an efficient and specific electron donor to PsPrxIIF in vivo.
      Other Trx-s tested by ITC analysis failed to interact with PsPrxIIF indicating a
      specific recognition of PsPrxIIF by Trx-o. PsPrxIIF exists primarily as a dimer
      or a hexamer depending on the redox state. In addition to the well-characterized
      oligomerization of classical 2-Cys Prx the results also show that atypical Prx
      undergo large structural reorganization with implications for protein-protein
      interaction and function.

PMID- 18632731
TI  - Application of a pilot control banding tool for risk level assessment and control
      of nanoparticle exposures.
AB  - Control banding (CB) strategies offer simplified solutions for controlling worker
      exposures to constituents that are found in the workplace in the absence of firm
      toxicological and exposure data. These strategies may be particularly useful in
      nanotechnology applications, considering the overwhelming level of uncertainty
      over what nanomaterials and nanotechnologies present as potential work-related
      health risks, what about these materials might lead to adverse toxicological
      activity, how risk related to these might be assessed and how to manage these
      issues in the absence of this information. This study introduces a pilot CB tool
      or 'CB Nanotool' that was developed specifically for characterizing the health
      aspects of working with engineered nanoparticles and determining the level of
      risk and associated controls for five ongoing nanotechnology-related operations
      being conducted at two Department of Energy research laboratories. Based on the
      application of the CB Nanotool, four of the five operations evaluated in this
      study were found to have implemented controls consistent with what was
      recommended by the CB Nanotool, with one operation even exceeding the required
      controls for that activity. The one remaining operation was determined to require
      an upgrade in controls. By developing this dynamic CB Nanotool within the realm
      of the scientific information available, this application of CB appears to be a
      useful approach for assessing the risk of nanomaterial operations, providing
      recommendations for appropriate engineering controls and facilitating the
      allocation of resources to the activities that most need them.

PMID- 18632732
TI  - LPA modulates monocyte migration directly and via LPA-stimulated endothelial
      cells.
AB  - Lysophosphatidic acid (LPA) is a bioactive lysophospholipid ligand present in
      oxidized low-density lipoprotein. The effects of LPA were investigated, first
      separately on endothelial cells (EC) and monocytes. Using Ki16425 (an LPA(1) and
      LPA(3) receptor antagonist), GW9662 [a peroxisome proliferator-activator receptor
      (PPARgamma) antagonist], and pertussis toxin (that inhibits G(i/o)), we
      demonstrate that LPA enhances IL-8 and monocyte chemoattractant protein-1
      expression through a LPA(1)-, LPA(3)-, G(i/o)- and PPARgamma-dependent manner in
      the EAhy926 cells. The effect of LPA on chemokine overexpression was confirmed in
      human umbilical vein endothelial cells. LPA was able to enhance monocyte
      migration at concentrations <1 microM and to inhibit their migration at LPA
      concentrations >1 microM, as demonstrated by using a chemotaxis assay. We then
      investigated the effects of LPA on the cross-talk between EC and monocytes by
      evaluating the chemotactic activity in the supernatants of LPA-treated EC. At 1
      microM LPA, both cell types respond cooperatively, favoring monocyte migration.
      At higher LPA concentration (25 microM), the chemotactic response varies as a
      function of time. After 4 h, the chemotactic effect of the cytokines secreted by
      the EC is counteracted by the direct inhibitory effect of LPA on monocytes. For
      longer periods of time (24 h), we observe a monocyte migration, probably due to
      lowered concentrations of bioactive LPA, given the induction of lipid phosphate
      phosphatase-2 in monocytes that may inactivate LPA. These results suggest that
      LPA activates EC to secrete chemokines that in combination with LPA itself might
      favor or not favor interactions between endothelium and circulating monocytes.

PMID- 18632733
TI  - Hypotonicity and peptide discharge from a single vesicle.
AB  - Neuroendocrine secretory vesicles discharge their cargo in response to a
      stimulus, but the nature of this event is poorly understood. We studied the
      release of the pituitary hormone prolactin by hypotonicity, because this hormone
      also contributes to osmoregulation. In perfused rat lactotrophs, hypotonicity
      resulted in a transient increase followed by a sustained depression of prolactin
      release, as monitored by radioimmunoassay. In single cells imaged by confocal
      microscopy, hypotonicity elicited discharge of the fluorescently labeled atrial
      natriuretic peptide cargo from approximately 2% of vesicles/cell. In contrast,
      KCl-induced depolarization resulted in a response of approximately 10% of
      vesicles/cell, with different unloading/loading time course of the two
      fluorescent probes. In cell-attached studies, discrete changes in membrane
      capacitance were recorded in both unstimulated and stimulated conditions,
      reflecting single vesicle fusion/fissions with the plasma membrane. In stimulated
      cells, the probability of occurrence of full fusion events was low and unchanged,
      whereas over 95% of fusion events were transient, with the open fusion pore
      probability, the average pore dwell-time, the frequency of occurrence, and the
      fusion pore conductance increased. Hypotonicity only rarely elicited new fusion
      events in silent membrane patches. The results indicate that, in hypotonicity
      stimulated lactotrophs, transient vesicle fusion mediates hormone release.

PMID- 18632734
TI  - Integrin VLA-4 enhances sialyl-Lewisx/a-negative melanoma adhesion to and
      extravasation through the endothelium under low flow conditions.
AB  - During their passage through the circulatory system, tumor cells undergo
      extensive interactions with various host cells including endothelial cells. The
      capacity of tumor cells to form metastasis is related to their ability to
      interact with and extravasate through endothelial cell layers, which involves
      multiple adhesive interactions between tumor cells and endothelium (EC). Thus it
      is essential to identify the adhesive receptors on the endothelial and melanoma
      surface that mediate those specific adhesive interactions. P-selectin and E
      selectin have been reported as adhesion molecules that mediate the cell-cell
      interaction of endothelial cells and melanoma cells. However, not all melanoma
      cells express ligands for selectins. In this study, we elucidated the molecular
      constituents involved in the endothelial adhesion and extravasation of sialyl
      Lewis(x/a)-negative melanoma cell lines under flow in the presence and absence of
      polymorphonuclear neutrophils (PMNs). Results show the interactions of
      alpha(4)beta(1) (VLA-4) on sialyl-Lewis(x/a)-negative melanoma cells and vascular
      adhesion molecule (VCAM-1) on inflamed EC supported melanoma adhesion to and
      subsequent extravasation through the EC in low shear flow. These findings provide
      clear evidence for a direct role of the VLA-4/VCAM-1 pathway in melanoma cell
      adhesion to and extravasation through the vascular endothelium in a shear flow.
      PMNs facilitated melanoma cell extravasation under both low and high shear
      conditions via the involvement of distinct molecular mechanisms. In the low shear
      regime, beta(2)-integrins were sufficient to enhance melanoma cell extravasation,
      whereas in the high shear regime, selectin ligands and beta(2)-integrins on PMNs
      were necessary for facilitating the melanoma extravasation process.

PMID- 18632735
TI  - Regulation of ERK1/2 by ouabain and Na-K-ATPase-dependent energy utilization and
      AMPK activation in parotid acinar cells.
AB  - We previously found that the phosphorylation of ERK1/2 by submaximal
      concentrations of the muscarinic receptor ligand carbachol was potentiated in rat
      parotid acinar cells exposed to ouabain, a cardiac glycoside that inhibits the Na
      K-ATPase. We now report that this signaling phenomenon involves the prevention of
      negative regulation of extracellular signal-regulated kinase-1/2 (ERK1/2) that is
      normally mediated by AMP-activated protein kinase (AMPK). Carbachol increases the
      turnover of the ATP-consuming Na-K-ATPase, reducing intracellular ATP and
      promoting the phosphorylation/activation of the energy sensor AMPK. Ouabain
      blocks the reduction in ATP and subsequent AMPK phosphorylation, which is
      regulated by the AMP-to-ATP ratio. The ouabain-promoted enhancement of ERK1/2
      phosphorylation was not reproduced in Par-C10 cells, an immortalized rat parotid
      cell line that did not respond to carbachol with an ATP reduction and that
      employs an upstream AMPK kinase (Ca(2+)/calmodulin-dependent protein kinase
      kinase, CaMKK) different from that (LKB1) in native cells. In native parotid
      cells, inhibitory effects of AMPK on ERK1/2 signaling were examined by activating
      AMPK with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), which
      is converted to an AMP mimetic but does not alter parotid ATP levels. AICAR
      treated cells display increases in AMPK phosphorylation and a reduced
      phosphorylation of ERK1/2 subsequent to activation of muscarinic and P2X(7)
      receptors, which promote increases in Na-K-ATPase turnover, but not upon
      epidermal growth factor receptor activation. These results suggest that carbachol
      initiated AMPK activation can produce a negative feedback on ERK1/2 signaling in
      response to submaximal muscarinic receptor activation and that increases in fluid
      secretion can modulate receptor-initiated signaling events indirectly by
      producing ion transport-dependent decreases in ATP.

PMID- 18632736
TI  - Identification and functional characterization of a novel human and rat
      riboflavin transporter, RFT1.
AB  - Absorption of riboflavin is mediated by transporter(s). However, a mammalian
      riboflavin transporter has yet to be identified. In the present study, the novel
      human and rat riboflavin transporters hRFT1 and rRFT1 were identified on the
      basis of our rat kidney mRNA expression database (Horiba N, Masuda S, Takeuchi A,
      Saito H, Okuda M, Inui K. Kidney Int 66: 29-45, 2004). hRFT1 and rRFT1 cDNAs have
      an open reading frame encoding 448- and 450-amino acid proteins, respectively,
      that exhibit 81.1% identity and 96.4% similarity to one another. In addition, an
      inactive splice variant of hRFT1, hRFT1sv, was also cloned. The hRFT1sv cDNA,
      which encodes a 167-amino acid protein, retains an intron between exons 2 and 3
      of hRFT1. Real-time PCR revealed that the sum of hRFT1 and hRFT1sv mRNAs was
      expressed strongly in the placenta and small intestine and was detected in all
      tissues examined. In addition, hRFT1 and hRFT1sv were expressed in human
      embryonic kidney (HEK)-293 and Caco-2 cells. HEK-293 cells transfected with green
      fluorescent protein-tagged hRFT1 and rRFT1 exhibited a fluorescent signal in the
      plasma membrane. Overexpression of hRFT1 and rRFT1, but not hRFT1sv, increased
      the cellular accumulation of [(3)H]riboflavin. The transfection of small
      interfering RNA targeting both hRFT1 and hRFT1sv significantly decreased the
      uptake of [(3)H]riboflavin by HEK-293 and Caco-2 cells. Riboflavin transport is
      Na(+), potential, and pH independent. Kinetic analyses demonstrated that the
      Michaelis-Menten constants for the uptake by HEK-293 and Caco-2 cells were 28.1
      and 63.7 nM, respectively. We propose that hRFT1 and rRFT1 are novel mammalian
      riboflavin transporters, which belong to a new mammalian riboflavin transporter
      family.

PMID- 18632738
TI  - Entorhinal cortex inhibits medial prefrontal cortex and modulates the activity
      states of electrophysiologically characterized pyramidal neurons in vivo.
AB  - The prefrontal cortex receives multiple inputs from the hippocampal complex,
      which are thought to drive memory-guided behavior. Moreover, dysfunctions of both
      regions have been repeatedly associated with several psychiatric disorders.
      Therefore, understanding the interconnections and modulatory interactions between
      these regions is essential in evaluating their role in behavior and pathology.
      The effects of entorhinal cortex (EC) stimulation on the activity of identified
      medial prefrontal cortex (mPFC) pyramidal neurons were examined using single-unit
      extracellular recordings and sharp-electrode intracellular recordings in
      anesthetized rats. Single-pulse electrical stimulation of EC induced a powerful
      inhibition in the majority of mPFC neurons examined during extracellular
      recording. Intracellular recording showed that EC stimulation evoked a complex
      synaptic response, in which the greater proportion of neurons exhibited
      excitatory postsynaptic events and/or a short lasting and a prolonged inhibitory
      postsynaptic response. Furthermore, stimulation of EC selectively produced an
      augmentation of the bistable up-down state only in the type 2 regular spiking
      neurons and in a subclass of nonintrinsic bursting neurons. Taken together, these
      data suggest that the potent inhibition observed following EC stimulation may
      mask a direct excitatory response within the mPFC which markedly potentiates the
      bistable states in a select subpopulation of mPFC pyramidal neurons.

PMID- 18632740
TI  - Widespread changes in dendritic spines in a model of Alzheimer's disease.
AB  - The mechanism by which dementia occurs in patients with Alzheimer's disease (AD)
      is not known. We assessed changes in hippocampal dendritic spines of APP/PS1
      transgenic mice that accumulate amyloid beta throughout the brain. Three
      dimensional analysis of 21,507 dendritic spines in the dentate gyrus, a region
      crucial for learning and memory, revealed a substantial decrease in the frequency
      of large spines in plaque-free regions of APP/PS1 mice. Plaque-related dendrites
      also show striking alterations in spine density and morphology. However, plaques
      occupy only 3.9% of the molecular layer volume. Because large spines are
      considered to be the physical traces of long-term memory, widespread decrease in
      the frequency of large spines likely contributes to the cognitive impairments
      observed in this AD model.

PMID- 18632739
TI  - The cortical signature of Alzheimer's disease: regionally specific cortical
      thinning relates to symptom severity in very mild to mild AD dementia and is
      detectable in asymptomatic amyloid-positive individuals.
AB  - Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable
      limbic and heteromodal regions of the cerebral cortex, detectable in vivo using
      magnetic resonance imaging. It is not clear whether abnormalities of cortical
      anatomy in AD can be reliably measured across different subject samples, how
      closely they track symptoms, and whether they are detectable prior to symptoms.
      An exploratory map of cortical thinning in mild AD was used to define regions of
      interest that were applied in a hypothesis-driven fashion to other subject
      samples. Results demonstrate a reliably quantifiable in vivo signature of
      abnormal cortical anatomy in AD, which parallels known regional vulnerability to
      AD neuropathology. Thinning in vulnerable cortical regions relates to symptom
      severity even in the earliest stages of clinical symptoms. Furthermore, subtle
      thinning is present in asymptomatic older controls with brain amyloid binding as
      detected with amyloid imaging. The reliability and clinical validity of AD
      related cortical thinning suggests potential utility as an imaging biomarker.
      This "disease signature" approach to cortical morphometry, in which disease
      effects are mapped across the cortical mantle and then used to define ROIs for
      hypothesis-driven analyses, may provide a powerful methodological framework for
      studies of neuropsychiatric diseases.

PMID- 18632741
TI  - Functional differentiation of macaque visual temporal cortical neurons using a
      parametric action space.
AB  - Neurons in the rostral superior temporal sulcus (STS) are responsive to displays
      of body movements. We employed a parametric action space to determine how
      similarities among actions are represented by visual temporal neurons and how
      form and motion information contributes to their responses. The stimulus space
      consisted of a stick-plus-point-light figure performing arm actions and their
      blends. Multidimensional scaling showed that the responses of temporal neurons
      represented the ordinal similarity between these actions. Further tests
      distinguished neurons responding equally strongly to static presentations and to
      actions ("snapshot" neurons), from those responding much less strongly to static
      presentations, but responding well when motion was present ("motion" neurons).
      The "motion" neurons were predominantly found in the upper bank/fundus of the
      STS, and "snapshot" neurons in the lower bank of the STS and inferior temporal
      convexity. Most "motion" neurons showed strong response modulation during the
      course of an action, thus responding to action kinematics. "Motion" neurons
      displayed a greater average selectivity for these simple arm actions than did
      "snapshot" neurons. We suggest that the "motion" neurons code for visual
      kinematics, whereas the "snapshot" neurons code for form/posture, and that both
      can contribute to action recognition, in agreement with computation models of
      action recognition.

PMID- 18632743
TI  - Integrative approaches for mining transcriptional regulatory programs in
      Arabidopsis.
AB  - Challenges in modern biology demand shifting focus from components-genes and
      proteins-to their interacting whole. Integrating information from multiple
      genomic datasets is seen as a means to this end, capable of providing robust and
      accurate ways to unravel these functional associations. Integrative strategies,
      both novel and adapted from other well-studied organisms, are being employed in
      the model plant Arabidopsis thaliana to interpret genome-wide expression,
      metabolic profiling and protein interaction studies. Exciting inroads are being
      made in mining and interpretation of developmental, physiological and
      environmental-response 'programs' using sequence and functional information. The
      fundamental transcriptional regulatory logic is emerging in Arabidopsis,
      presently revealed as isolated conditional, spatial or temporal regulatory
      'modules'. This immediately calls for efforts towards assembling these building
      blocks together into a unifying model, thus creating standards for future work to
      compare with. As a young field, Arabidopsis systems biology is ripe with such an
      opportunity, now scarcely realizable in other model organisms.

PMID- 18632742
TI  - Neuregulin-1 modulates hippocampal gamma oscillations: implications for
      schizophrenia.
AB  - Alterations in gamma-frequency oscillations are implicated in psychiatric
      disorders, and polymorphisms in NRG-1 and ERBB4, genes encoding Neuregulin-1 (NRG
      1) and one of its receptors, designated ErbB4, are associated with schizophrenia.
      Here we show that NRG-1 selectively increases the power of kainate-induced, but
      not carbachol-induced, gamma oscillations in acute hippocampal slices. NRG-1beta
      is more effective than NRG-1alpha, a splice variant with lower affinity for ErbB
      receptors, and neither isoform affects the network activity without prior
      induction of gamma oscillations. NRG-1beta dramatically increases gamma
      oscillation power in hippocampal slices from both rats (2062 +/- 496%) and mice
      (710 +/- 299%). These effects of NRG-1beta are blocked by PD158780, a pan
      specific antagonist of ErbB receptors, and are mediated specifically via ErbB4
      receptors, because mice harboring a targeted mutation of ErbB4 do not respond to
      NRG-1. Moreover, we demonstrate that 50% of gamma-amino butyric acidergic
      parvalbumin (PV)-positive interneurons, which heavily contribute to the
      generation of gamma oscillations, express ErbB4 receptors. Importantly, both the
      number of PV-immunoreactive interneurons (-31%) and the power of kainate-induced
      gamma oscillations (-60%) are reduced in ErbB4 knockout mice. This study provides
      the first plausible link between NRG-1/ErbB4 signaling and rhythmic network
      activity that may be altered in persons with schizophrenia.

PMID- 18632745
TI  - Relation between peak structures of loss functions of single double-walled carbon
      nanotubes and interband transition energies.
AB  - Electron energy-loss spectra of single double-walled carbon nanotubes (DWCNTs)
      were compared with calculated joint density of states (jDOSs) obtained by a
      simple tight-binding (STB) and an extended tight-binding (ETB) method. From the
      comparisons, interband transition energies of ETB calculations show better
      agreement with peak positions of the experimental spectra than those of STB
      results. From a further comparison among calculated jDOS, real and imaginary
      parts of a dielectric function and a loss function Im[-1/epsilon], it was
      confirmed that the peak energies in a spectrum of single DWCNTs are almost equal
      to those of the optical absorption spectrum epsilon(2).

PMID- 18632744
TI  - Strategies for manufacturing recombinant adeno-associated virus vectors for gene
      therapy applications exploiting baculovirus technology.
AB  - The development of recombinant adeno-associated virus (rAAV) gene therapy
      applications is hampered by the inability to produce rAAV in sufficient
      quantities to support pre-clinical and clinical trials. Contrasting with adherent
      cell cultures, suspension cultures provide a straightforward means for expansion,
      however, transiently expressing the necessary, but cytotoxic virus proteins
      remains the challenge for rAAV production. Both the expansion and expression
      issues are resolved by using the baculovirus expression vector (bev) and insect
      cell culture system. This review addresses strategies for the production of rAAV
      exploiting baculovirus technology at different scales using different
      configurations of bioreactors as well as processing and product characterization
      issues. The yields obtained with these optimized processes exceed approximately 1
      x 10(14) vector particles per liter of cell culture suitable for pre-clinical and
      clinical trials and possible commercialization.

PMID- 18632746
TI  - Scanning electron microscopic observation of the sensory region in the frog
      muscle spindle.
AB  - The equatorial sensory region of muscle spindles in the fourth toe extensor
      digitorum longus muscle of the adult frog was examined by scanning electron
      microscopy. Segments of this thin and long muscle after fixation were
      longitudinally cut with a razor blade and then treated with an HCl-hydrolysis
      method to remove connective tissues. Cells of the inner capsule extended thin and
      flattened cytoplasmic processes, showing a sieve-like appearance. Some specimens
      after a partial disruption of the inner capsule reevaluated at the fine
      structural level that numerous sensory terminals with varicose swellings
      longitudinally arranged along each intrafusal muscle fiber.

PMID- 18632747
TI  - Apparently low reproducibility of true differential expression discoveries in
      microarray studies.
AB  - MOTIVATION: Differentially expressed gene (DEG) lists detected from different
      microarray studies for a same disease are often highly inconsistent. Even in
      technical replicate tests using identical samples, DEG detection still shows very
      low reproducibility. It is often believed that current small microarray studies
      will largely introduce false discoveries. RESULTS: Based on a statistical model,
      we show that even in technical replicate tests using identical samples, it is
      highly likely that the selected DEG lists will be very inconsistent in the
      presence of small measurement variations. Therefore, the apparently low
      reproducibility of DEG detection from current technical replicate tests does not
      indicate low quality of microarray technology. We also demonstrate that
      heterogeneous biological variations existing in real cancer data will further
      reduce the overall reproducibility of DEG detection. Nevertheless, in small
      subsamples from both simulated and real data, the actual false discovery rate
      (FDR) for each DEG list tends to be low, suggesting that each separately
      determined list may comprise mostly true DEGs. Rather than simply counting the
      overlaps of the discovery lists from different studies for a complex disease,
      novel metrics are needed for evaluating the reproducibility of discoveries
      characterized with correlated molecular changes. Supplementaty information:
      Supplementary data are available at Bioinformatics online.

PMID- 18632748
TI  - EPoS: a modular software framework for phylogenetic analysis.
AB  - Estimating Phylogenies of Species (EPoS) is a modular software framework for
      phylogenetic analysis, visualization and data management. It provides a plugin
      based system that integrates a storage facility, a rich user interface and the
      ability to easily incorporate new methods, functions and visualizations. EPoS
      ships with persistent data management, a set of well-known phylogenetic
      algorithms and a multitude of tree visualization methods and layouts. Implemented
      algorithms cover distance-based tree construction, consensus trees and various
      graph-based supertree methods. The rendering system can be customized for, say,
      different edge and node styles.

PMID- 18632749
TI  - Accurate prediction of stability changes in protein mutants by combining machine
      learning with structure based computational mutagenesis.
AB  - MOTIVATION: Accurate predictive models for the impact of single amino acid
      substitutions on protein stability provide insight into protein structure and
      function. Such models are also valuable for the design and engineering of new
      proteins. Previously described methods have utilized properties of protein
      sequence or structure to predict the free energy change of mutants due to thermal
      (DeltaDeltaG) and denaturant (DeltaDeltaG(H2O)) denaturations, as well as mutant
      thermal stability (DeltaT(m)), through the application of either computational
      energy-based approaches or machine learning techniques. However, accuracy
      associated with applying these methods separately is frequently far from optimal.
      RESULTS: We detail a computational mutagenesis technique based on a four-body,
      knowledge-based, statistical contact potential. For any mutation due to a single
      amino acid replacement in a protein, the method provides an empirical normalized
      measure of the ensuing environmental perturbation occurring at every residue
      position. A feature vector is generated for the mutant by considering
      perturbations at the mutated position and it's ordered six nearest neighbors in
      the 3-dimensional (3D) protein structure. These predictors of stability change
      are evaluated by applying machine learning tools to large training sets of
      mutants derived from diverse proteins that have been experimentally studied and
      described. Predictive models based on our combined approach are either comparable
      to, or in many cases significantly outperform, previously published results.
      AVAILABILITY: A web server with supporting documentation is available at
      http://proteins.gmu.edu/automute.

PMID- 18632750
TI  - Automated annotation of Drosophila gene expression patterns using a controlled
      vocabulary.
AB  - MOTIVATION: Regulation of gene expression in space and time directs its
      localization to a specific subset of cells during development. Systematic
      determination of the spatiotemporal dynamics of gene expression plays an
      important role in understanding the regulatory networks driving development. An
      atlas for the gene expression patterns of fruit fly Drosophila melanogaster has
      been created by whole-mount in situ hybridization, and it documents the dynamic
      changes of gene expression pattern during Drosophila embryogenesis. The spatial
      and temporal patterns of gene expression are integrated by anatomical terms from
      a controlled vocabulary linking together intermediate tissues developed from one
      another. Currently, the terms are assigned to patterns manually. However, the
      number of patterns generated by high-throughput in situ hybridization is rapidly
      increasing. It is, therefore, tempting to approach this problem by employing
      computational methods. RESULTS: In this article, we present a novel computational
      framework for annotating gene expression patterns using a controlled vocabulary.
      In the currently available high-throughput data, annotation terms are assigned to
      groups of patterns rather than to individual images. We propose to extract
      invariant features from images, and construct pyramid match kernels to measure
      the similarity between sets of patterns. To exploit the complementary information
      conveyed by different features and incorporate the correlation among patterns
      sharing common structures, we propose efficient convex formulations to integrate
      the kernels derived from various features. The proposed framework is evaluated by
      comparing its annotation with that of human curators, and promising performance
      in terms of F1 score has been reported.

PMID- 18632751
TI  - BioBayes: a software package for Bayesian inference in systems biology.
AB  - MOTIVATION: There are several levels of uncertainty involved in the mathematical
      modelling of biochemical systems. There often may be a degree of uncertainty
      about the values of kinetic parameters, about the general structure of the model
      and about the behaviour of biochemical species which cannot be observed directly.
      The methods of Bayesian inference provide a consistent framework for modelling
      and predicting in these uncertain conditions. We present a software package for
      applying the Bayesian inferential methodology to problems in systems biology.
      RESULTS: Described herein is a software package, BioBayes, which provides a
      framework for Bayesian parameter estimation and evidential model ranking over
      models of biochemical systems defined using ordinary differential equations. The
      package is extensible allowing additional modules to be included by developers.
      There are no other such packages available which provide this functionality.

PMID- 18632752
TI  - Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and
      chemoresistance of ovarian cancer cells.
AB  - The RAS-RAF-MEK-extracellular signal-regulated kinase (ERK) pathway plays a
      pivotal role in various cellular responses, including cellular growth,
      differentiation, survival and motility. Constitutive activation of the ERK
      pathway has been linked to the development and progression of human cancers.
      Here, we reported that mitogen-activated protein kinase phosphatase (MKP)-3, a
      negative regulator of ERK1/2, lost its expression particularly in the protein
      level, was significantly correlated with high ERK1/2 activity in primary human
      ovarian cancer cells using quantitative reverse transcription-polymerase chain
      reaction and western blot analyses. Intriguingly, the loss of MKP3 protein was
      associated with ubiquitination/proteosome degradation mediated by high
      intracellular reactive oxygen species (ROS) accumulation such as hydrogen
      peroxide in ovarian cancer cells. Functionally, short hairpin RNA knock down of
      endogenous MKP3 resulted in increased ERK1/2 activity, cell proliferation rate,
      anchorage-independent growth ability and resistance to cisplatin in ovarian
      cancer cells. Conversely, enforced expression of MKP3 in MKP3-deficient ovarian
      cancer cells significantly reduced ERK1/2 activity and inhibited cell
      proliferation, anchorage-independent growth ability and tumor development in nude
      mice. Furthermore, the enforced expression of MKP3 succeeded to sensitize ovarian
      cancer cells to cisplatin-induced apoptosis in vitro and in vivo. These results
      suggest a molecular mechanism by which the accumulation of ROS during ovarian
      cancer progression may cause the degradation of MKP3, which in turn leads to
      aberrant ERK1/2 activation and contributes to tumorigenicity and chemoresistance
      of human ovarian cancer cells.

PMID- 18632753
TI  - Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes.
AB  - Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens
      present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1
      metabolizing genes are associated with increased bladder cancer risk. We
      evaluated whether genetic variation in other candidate metabolizing genes are
      also associated with risk. Candidates included genes that control the
      transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and
      aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA
      or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4,
      SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial
      carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated
      odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender,
      region and smoking status. Based on a test for trend, we observed 10 non
      redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT,
      CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We
      observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845
      [OR (95% CI) for heterozygote and homozygote variant compared with common
      homozygote genotype were 0.86 (0.70-1.06) and 0.74 (0.57-0.96), respectively; P
      for trend = 0.02]. Interestingly, genetic variation in this region has been
      associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of
      additional SNPs to capture most (approximately 90%) of common genetic variation
      in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25)
      suggest two separate regions associated with bladder cancer risk. These results
      indicate that genetic variation in carcinogen-metabolizing genes, particularly
      AKR1C3, could be associated with bladder cancer risk.

PMID- 18632755
TI  - The renin-angiotensin system and malignancy.
AB  - The renin-angiotensin system (RAS) is usually associated with its systemic action
      on cardiovascular homoeostasis. However, recent studies suggest that at a local
      tissue level, the RAS influences tumour growth. The potential of the RAS as a
      target for cancer treatment and the suggested underlying mechanisms of its
      paracrine effects are reviewed here. These include modulation of angiogenesis,
      cellular proliferation, immune responses and extracellular matrix formation.
      Knowledge of the RAS has increased dramatically in recent years with the
      discovery of new enzymes, peptides and feedback mechanisms. The local RAS appears
      to influence tumour growth and metastases and there is evidence of tissue- and
      tumour-specific differences. Recent experimental studies provide strong evidence
      that drugs that inhibit the RAS have the potential to reduce cancer risk or
      retard tumour growth and metastases. Manipulation of the RAS may, therefore,
      provide a safe and inexpensive anticancer strategy.

PMID- 18632754
TI  - Dietary genistein negates the inhibitory effect of letrozole on the growth of
      aromatase-expressing estrogen-dependent human breast cancer cells (MCF-7Ca) in
      vivo.
AB  - Genistein (GEN), a soy isoflavone, stimulates growth of estrogen-dependent human
      tumor cells (MCF-7) in a preclinical mouse model for postmenopausal breast
      cancer. Antiestrogens and aromatase inhibitors are frontline therapies for
      estrogen-dependent breast cancer. We have demonstrated that dietary GEN can
      negate the inhibitory effect of tamoxifen. In this study, we evaluated the
      interaction of dietary GEN (at 250-1000 p.p.m. in the American Institute of
      Nutrition 93 growth diet) and an aromatase inhibitor, letrozole (LET), on the
      growth of tumors in an aromatase-expressing breast cancer xenograft model (MCF
      7Ca) in the presence and absence of the substrate androstenedione (AD). Dietary
      GEN (250 and 500 p.p.m.) or implanted AD stimulated MCF-7Ca tumor growth.
      Implanted LET inhibited AD-stimulated MCF-7Ca tumor growth. In the presence of AD
      and LET, dietary GEN (250, 500 and 1000 p.p.m.) reversed the inhibitory effect of
      LET in a dose-dependent manner. Uterine wet weight, plasma estradiol (E(2))
      levels (enzyme-linked immunosorbent assay) and total plasma GEN and LET levels
      (liquid chromatography-electrospray/tandem mass spectrometry) were measured. Ki
      67 (cellular proliferation), aromatase and pS2 protein expression in tumors were
      evaluated using immunohistochemical (IHC) analysis. In conclusion, dietary GEN
      increased the growth of MCF-7Ca tumors implanted in ovariectomized mice and could
      also negate the inhibitory effect of LET on MCF-7Ca tumor growth. These findings
      are significant because tumors, which express aromatase and synthesize estrogen,
      are good candidates for aromatase therapy dietary and GEN can reverse the
      inhibitory effect of LET on tumor growth and adversely impact breast cancer
      therapy. Caution is warranted for consumption of dietary GEN by postmenopausal
      women with estrogen-dependent breast cancer taking LET treatment.

PMID- 18632756
TI  - Variable DNA methylation patterns associated with progression of disease in
      hepatocellular carcinomas.
AB  - Hepatocellular carcinoma (HCC) most commonly arises from chronic inflammation due
      to viral infection, as a result of genetic and epigenetic abnormalities. A global
      picture of epigenetic changes in HCC is lacking. We used methylated CpG island
      amplification microarrays (MCAMs) to study 6458 CpG islands in HCC and adjacent
      preneoplastic tissues [chronic hepatitis (CH) or liver cirrhosis (LC)] in
      comparison with normal liver tissues where neither viral infection nor hepatitis
      has existed. MCAM identified 719 (11%) prominent genes of hypermethylation in
      HCCs. HCCs arising from LC had significantly more methylation than those arising
      from CH (1249 genes or 19% versus 444 genes or 7%, P < 0.05). There were four
      patterns of aberrant methylation: Type I (4%, e.g. matrix metalloproteinase 14)
      shows a substantially high methylation level in adjacent tissue and does not
      increase further in cancer. Type II (55%, e.g. RASSF1A) shows progressively
      increasing methylation from adjacent tissue to HCC. Type III (4%, e.g. GNA14)
      shows decreased methylation in adjacent tissue but either similar or increased
      methylation in HCC. Type IV (37%, e.g. CDKN2A) shows low levels of methylation in
      normal tissue and adjacent tissue but high levels in HCC. These DNA methylation
      changes were confirmed by quantitative pyrosequencing methylation analysis in
      representative 24 genes and were analyzed for correlation with
      clinicopathological parameters in 38 patients. Intriguingly, methylation in the
      Type IV genes is characteristic of moderately/poorly differentiated cancer. Our
      global epigenome analysis reveals distinct patterns of methylation that are
      probably to represent different pathophysiologic processes in HCCs.

PMID- 18632757
TI  - Aberrant promoter hypermethylation in serum DNA from patients with silicosis.
AB  - It is well established that patients with silicosis are at high risk for lung
      cancer; however, it is difficult to detect lung cancer by chest radiography
      during follow-up treatment of patients with silicosis because of preexisting
      diffuse pulmonary shadows. The purpose of this study is to evaluate the
      usefulness of detection of serum DNA methylation for early detection of lung
      cancer in silicosis. Serum samples from healthy controls (n = 20) and silicosis
      patients with (n = 11) and without (n = 67) lung cancer were tested for aberrant
      hypermethylation at the promoters of the DNA repair gene O(6)-methylguanine-DNA
      methyltransferase (MGMT), p16(INK4a), ras association domain family 1A (RASSF1A),
      the apoptosis-related gene death-associated protein kinase (DAPK) and retinoic
      acid receptor beta (RARbeta) by methylation-specific polymerase chain reaction.
      Aberrant promoter methylation in at least one of five tumor suppressor genes was
      detected more frequently in the serum DNA of silicosis patients with lung cancer
      than in that of patients without it (P = 0.006). Furthermore, the odds ratio of
      having lung cancer was 9.77 (P = 0.009) for those silicosis patients with
      methylation of at least one gene. Extended exposure to silica (>30 years) was
      correlated with an increased methylation frequency (P = 0.017); however,
      methylation status did not correlate with age, smoking history or radiographic
      findings of silicosis. These results suggest that testing for aberrant promoter
      methylation of tumor suppressor genes using serum DNA may facilitate early
      detection of lung cancer in patients with silicosis.

PMID- 18632758
TI  - MN1 affects expression of genes involved in hematopoiesis and can enhance as well
      as inhibit RAR/RXR-induced gene expression.
AB  - The oncoprotein meningioma 1 (MN1) is overexpressed in several subtypes of acute
      myeloid leukemia (AML) and overexpression was associated with a poor response to
      chemotherapy. MN1 is a cofactor of retinoic acid receptor/retinoic x receptor
      (RAR/RXR)-mediated transcription and this study identified genes in the
      promonocytic cell line U937 that were regulated by MN1. We found that MN1 can
      both stimulate and inhibit transcription. Combining MN1 expression with all-trans
      retinoic acid (ATRA), the ligand of the RAR/RXR dimer, showed that MN1 could both
      enhance and repress ATRA effects. Many of the identified genes are key players in
      hematopoiesis and leukemogenesis (e.g. MEIS1 and BMI1). Another interesting
      target is DHRS9. DHRS9 is involved in the synthesis of ATRA from vitamin A. MN1
      inhibited DHRS9 expression and completely abolished its induction by ATRA. MN1 is
      also the target of a rare AML-causing translocation encoding the MN1-TEL protein.
      MN1-TEL induces expression of only a few genes and its most pronounced effect is
      inhibition of a large group of ATRA-induced genes including DHRS9. In conclusion,
      both MN1 and MN1-TEL interfere with the ATRA pathway and this might explain the
      differentiation block in leukemias in which these genes are involved.

PMID- 18632759
TI  - Efficient transfer of base changes from a vector to the rice genome by homologous
      recombination: involvement of heteroduplex formation and mismatch correction.
AB  - Gene targeting refers to the alteration of a specific DNA sequence in an
      endogenous gene at its original locus in the genome by homologous recombination.
      Through a gene-targeting procedure with positive-negative selection, we
      previously reported the generation of fertile transgenic rice plants with a
      positive marker inserted into the Adh2 gene by using an Agrobacterium-mediated
      transformation vector containing the positive marker flanked by two 6-kb
      homologous segments for recombination. We describe here that base changes within
      the homologous segments in the vector could be efficiently transferred into the
      corresponding genomic sequences of rice recombinants. Interestingly, a few
      sequences from the host genome were flanked by the changed sequences derived from
      the vector in most of the recombinants. Because a single-stranded T-DNA molecule
      in Agrobacterium-mediated transformation is imported into the plant nucleus and
      becomes double-stranded, both single-stranded and double-stranded T-DNA
      intermediates can serve in gene-targeting processes. Several alternative models,
      including the occurrence of the mismatch correction of heteroduplex molecules
      formed between the genomic DNA and either a single-stranded or double-stranded T
      DNA intermediate, are compared to explain the observation, and implications for
      the modification of endogenous genes for functional genomic analysis by gene
      targeting are discussed.

PMID- 18632760
TI  - Intronically encoded siRNAs improve dynamic range of mammalian gene regulation
      systems and toggle switch.
AB  - Applications of conditional gene expression, whether for therapeutic or basic
      research purposes, are increasingly requiring mammalian gene control systems that
      exhibit far tighter control properties. While numerous approaches have been used
      to improve the widely used Tet-regulatory system, many applications, particularly
      with respect to the engineering of synthetic gene networks, will require a
      broader range of tightly performing gene control systems. Here, a generically
      applicable approach is described that utilizes intronically encoded siRNA on the
      relevant transregulator construct, and siRNA sequence-specific tags on the
      reporter construct, to minimize basal gene activity in the off-state of a range
      of common gene control systems. To demonstrate tight control of residual
      expression the approach was successfully used to conditionally express the toxic
      proteins RipDD and Linamarase. The intronic siRNA concept was also extended to
      create a new generation of compact, single-vector, autoinducible siRNA vectors.
      Finally, using improved regulation systems a mammalian epigenetic toggle switch
      was engineered that exhibited superior in vitro and in vivo induction
      characteristics in mice compared to the equivalent non-intronic system.

PMID- 18632761
TI  - Features of 80S mammalian ribosome and its subunits.
AB  - It is generally believed that basic features of ribosomal functions are
      universally valid, but a systematic test still stands out for higher eukaryotic
      80S ribosomes. Here we report: (i) differences in tRNA and mRNA binding
      capabilities of eukaryotic and bacterial ribosomes and their subunits. Eukaryotic
      40S subunits bind mRNA exclusively in the presence of cognate tRNA, whereas
      bacterial 30S do bind mRNA already in the absence of tRNA. 80S ribosomes bind
      mRNA efficiently in the absence of tRNA. In contrast, bacterial 70S interact with
      mRNA more productively in the presence rather than in the absence of tRNA. (ii)
      States of initiation (P(i)), pre-translocation (PRE) and post-translocation
      (POST) of the ribosome were checked and no significant functional differences to
      the prokaryotic counterpart were observed including the reciprocal linkage
      between A and E sites. (iii) Eukaryotic ribosomes bind tetracycline with an
      affinity 15 times lower than that of bacterial ribosomes (K(d) 30 microM and 1-2
      microM, respectively). The drug does not effect enzymatic A-site occupation of
      80S ribosomes in contrast to non-enzymatic tRNA binding to the A-site. Both
      observations explain the relative resistance of eukaryotic ribosomes to this
      antibiotic.

PMID- 18632762
TI  - Phosphorylation of the carboxy-terminal domain of histone H1: effects on
      secondary structure and DNA condensation.
AB  - Linker histone H1 plays an important role in chromatin folding. Phosphorylation
      by cyclin-dependent kinases is the main post-translational modification of
      histone H1. We studied the effects of phosphorylation on the secondary structure
      of the DNA-bound H1 carboxy-terminal domain (CTD), which contains most of the
      phosphorylation sites of the molecule. The effects of phosphorylation on the
      secondary structure of the DNA-bound CTD were site-specific and depended on the
      number of phosphate groups. Full phosphorylation significantly increased the
      proportion of beta-structure and decreased that of alpha-helix. Partial
      phosphorylation increased the amount of undefined structure and decreased that of
      alpha-helix without a significant increase in beta-structure. Phosphorylation had
      a moderate effect on the affinity of the CTD for the DNA, which was proportional
      to the number of phosphate groups. Partial phosphorylation drastically reduced
      the aggregation of DNA fragments by the CTD, but full phosphorylation restored to
      a large extent the aggregation capacity of the unphosphorylated domain. These
      results support the involvement of H1 hyperphosphorylation in metaphase chromatin
      condensation and of H1 partial phosphorylation in interphase chromatin
      relaxation. More generally, our results suggest that the effects of
      phosphorylation are mediated by specific structural changes and are not simply a
      consequence of the net charge.

PMID- 18632764
TI  - Cities, urbanization and health.

PMID- 18632763
TI  - Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at
      clinically relevant Adriamycin concentrations.
AB  - Limited sensitivity of existing assays has prevented investigation of whether
      Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin.
      Previous detection has achieved a sensitivity of a few Adriamycin-DNA
      adducts/10(4) bp DNA, but has required the use of supra-clinical drug
      concentrations. This work sought to measure Adriamycin-DNA adducts at sub
      micromolar doses using accelerator mass spectrometry (AMS), a technique with
      origins in geochemistry for radiocarbon dating. We have used conditions
      previously validated (by less sensitive decay counting) to extract
      [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS
      detection. Here we show the first direct evidence of Adriamycin-DNA adducts at
      clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25
      nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell)
      in MCF-7 breast cancer cells, representing the best sensitivity and precision
      reported to date for the covalent binding of Adriamycin to DNA. The exceedingly
      sensitive nature of AMS has enabled over three orders of magnitude increased
      sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation
      within an hour of drug treatment. This method has been shown to be highly
      reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in
      culture and can now be applied to the detection of these adducts in human
      tissues.

PMID- 18632765
TI  - Alternate site pacing in patients at risk for heart failure.
AB  - Cardiac pacing from the right ventricular apex is the most common site of cardiac
      pacing. During the last decade, several studies demonstrated the harmful effects
      of the iatrogenic left bundle branch block, which is observed in cardiac pacing
      from the right ventricular apex. These observations led to an interest in
      alternative right ventricular pacing sites aiming to achieve a more
      "physiological" pattern of ventricular activation. Alternate site pacing may
      involve His bun- dle, other right ventricular sites (outflow or septal sites), or
      left ventricular sites in either unifocal or bifocal or biventricular modes.
      Pacing from the right ventricular outflow tract has been studied extensively.
      Several studies showed that right ventricular outflow tract pacing has better
      hemodynamic effects and less harmful influence. Bifocal right ventricular (apical
      and outflow tract) pacing has been proposed for patients with heart failure where
      the coronary sinus approach to effect biventricular pacing turns out to be
      unsuccessful because of various reasons. Some studies examined left ventricular
      pacing alone as an alternative mode of pacing, and the results were quite
      encouraging but not conclusive. Finally, in heart failure patients not responding
      to biventricular pacing, the triple site pacing mode has been recently proposed.
      In triple site pacing, the leads are inserted in the right ventricular apex and
      outflow tract in conjunction with lateral left ventricular pacing. Improvement of
      exercise capacity and increased ejection fraction were observed with this
      triventricular pacing. Although more data from specifically designed randomized
      studies are needed, there are many alternative pacing sites, especially for
      patients at high risk of heart failure, which seems to be less harmful and better
      tolerated by the patients.

PMID- 18632766
TI  - Lipidomics-based safety biomarkers for lipid-lowering treatments.
AB  - Recent data suggest that aggressive lipid-lowering treatment results in
      significant reductions of atherosclerotic complications, ie, strokes, heart
      attacks, or peripheral vascular diseases. Thus, more patients will be titrated to
      higher doses of statins in order to reach the aggressive targets of low-density
      lipoprotein- cholesterol reduction. However, aggressive treatment with high
      statin doses has increased the risk of statin-induced myopathy. The incidence of
      myopathy in cohort studies and in randomized trials has been low, supporting the
      good safety profile of statin drugs. However, muscle effects seem to be more
      frequent in clinical practice. Of all statin users, approximately 1% to 5%
      suffers from muscular symptoms caused by medication. This potentially reduces the
      compliance toward treatment and number of patients reaching their treatment
      targets due to withdrawal of therapy. Thus, novel biomarkers are needed for
      prediction or improved diagnoses of statin-induced side effects. This would
      potentially increase the quality of life of patients and improve treatment
      results. Using lipidomic analysis, we found that the plasma lipidomic changes
      following simvastatin treatment correlate with the muscle expression of the
      arachidonate 5-lipoxygenase-activating protein. Intriguingly, these results
      suggest that the plasma lipidomic profile may serve as a highly sensitive
      biomarker of statin-induced metabolic alterations in muscle and may thus allow us
      to identify patients who should be treated with a lower dose to prevent a
      possible toxicity.

PMID- 18632767
TI  - Somatosensory pulsatile tinnitus syndrome: somatic testing identifies a pulsatile
      tinnitus subtype that implicates the somatosensory system.
AB  - A new tinnitus syndrome is described: high-pitched, cardiac-synchronous tinnitus,
      whose pulsations are suppressed by strong contractions or compressions of the
      neck and jaw muscles (somatic testing). 14 cases, 6 non-lateralized and 8
      unilateral, are reported. In the non-lateralized cases, onset was bilateral. In
      the one intermittent case, while her tinnitus was absent her pulsatile tinnitus
      could be induced by somatic testing. No etiology was found from physical
      examination, imaging, or ancillary testing. Because these cases of pulsatile
      tinnitus can be both induced and suppressed by activation of the somatosensory
      system of the head or upper lateral neck, we propose that this syndrome is
      occurring from (a) cardiac synchronous somatosensory activation of the central
      auditory pathway or (b) failure of the somatosensory-auditory central nervous
      system interactions to suppress cardiac somatosounds.

PMID- 18632768
TI  - PHEMA hydrogels modified through the grafting of phosphate groups by ATRP support
      the attachment and growth of human corneal epithelial cells.
AB  - Converting the surface of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel into
      a cell-adhesive surface has been successfully achieved through a method based on
      atom transfer radical polymerization (ATRP) grafting. Following activation of the
      surface hydroxyl groups of PHEMA by bromination, surface-initiated ATRP of mono(2
      methacryloyloxyethyl) phosphate (MMEP) was conducted in a methanol-water system
      with Cu(I)Br as catalyst at room temperature. The conversion of PHEMA hydroxyl
      groups to brominated isobutyryl groups and the occurrence of grafting of PMMEP
      were confirmed by infrared and X-ray photoelectron spectroscopies. Cell
      attachment experiments were conducted by culturing human corneal limbal
      epithelial cells on the PMMEP-grafted PHEMA, and on unmodified PHEMA and tissue
      culture plastic for comparison. The results showed that the grafted PMMEP was
      homogeneously distributed, and the phosphate groups appeared to significantly
      promote the attachment, spreading and growth of cells, at a level comparable to
      the tissue culture plastic.

PMID- 18632769
TI  - Structured drug-eluting bioresorbable films: microstructure and release profile.
AB  - Bioresorbable drug-eluting films can be used in many biomedical applications.
      Examples for such applications include biodegradable medical support devices
      which combine mechanical support with drug release and antibiotic-eluting film
      coatings for prevention of bacterial infections associated with orthopedic
      implants or during gingival healing. In the current study, bioresorbable drug
      loaded polymer films are prepared by solution processing. Two film structures are
      studied: A polymer film with large drug crystals located on its surface (A-type)
      and a polymer film with small drug particles and crystals distributed within the
      bulk (B-type). The basic mode of drug dispersion/location in the film (A or B
      type) is found to be determined mainly by the process of film formation and
      depends mainly on the solvent evaporation rate, whereas the drug's hydrophilicity
      has a minor effect on this structuring process. Most release profiles from A-type
      films exhibit a burst effect of approximately 30% and a second release stage that
      occurs at an approximately constant rate and is determined mainly by the polymer
      weight loss rate. An extremely high burst release is exhibited only by a very
      hydrophilic drug. The matrix (monolithic) nature of the B-type film enables
      release profiles that are determined mainly by the host polymer's degradation
      profile, with a very low burst effect in most of the studied systems. In addition
      to the drug location/ dispersion in the film, the host polymer and drug type also
      strongly affect the drug's release profile from the film. It has been
      demonstrated that appropriate selection of the process parameters and film
      components (polymer and drug) can yield film structures with desirable drug
      release behaviors. This can lead to the engineering of new bioresorbable drug
      eluting film-based implants for various applications.

PMID- 18632770
TI  - Effect of platelet-rich plasma on the in vitro proliferation and osteogenic
      differentiation of human mesenchymal stem cells on distinct calcium phosphate
      scaffolds: the specific surface area makes a difference.
AB  - The in vitro effect of platelet-rich plasma (PRP) on cell loading, proliferation,
      and osteogenic differentiation of human mesenchymal stem cells (MSC) is assessed
      on distinct resorbable and synthetic calcium phosphate scaffolds. A high specific
      surface area scaffold composed of calcium-deficient hydroxyapatite (CDHA; 48m2/g)
      is compared with one made out of beta-tricalcium phosphate (beta-TCP; surface
      area <0.5 m2/g). Fivefold concentrated fresh PRP is applied to scaffolds loaded
      with 2 x 10(5) MSC (n = 5). These constructs are kept in a medium with osteogenic
      supplements for 3 weeks. The addition of PRP leads to a higher cell loading
      efficiency of MSC on CDHA (p = 0.0001), that reaches the values of beta-TCP.
      Proliferation over 21 days is improved by PRP both on CDHA (p = 0.0001) and beta
      TCP (p = 0.014) compared to MSC/calcium phosphate composites. Without the
      addition of PRP, CDHA has a lower cell loading efficiency (p= 0.0001) and
      proliferation (p= 0.001) than beta-TCP. The ALP activity is higher in the
      MSC/ceramics groups than in the monolayer controls (p<0.05). The addition of PRP
      does not significantly affect ALP activity. However, ALP activity varies
      considerably within the cell donors and different PRP-pools (p = 0.001), while
      the cell numbers do not vary within these two parameters. PRP generates a
      positive effect on the loading efficiency of MSC on the high specific surface
      scaffold CDHA that thereby reaches the loading efficiency of beta-TCP. PRP
      improved proliferation, but its osteogenic properties on both calcium phosphate
      scaffolds are weak.

PMID- 18632771
TI  - In vivo response of bioactive PMMA-based bone cement modified with alkoxysilane
      and calcium acetate.
AB  - The use of polymethylmethacrylate (PMMA)-based bone cement is popular in
      orthopedics for the fixation of artificial joints with bone. However, it has a
      major problem with prostheses loosening because of coverage by fibrous tissue
      after long-term implantation. Recently, a bioactive bone cement has been
      developed that shows direct bonding to living bone through modification of PMMA
      resin with gamma-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate.
      The cement is designed to exhibit bioactivity, through incorporation of silanol
      groups and calcium ions. Thus, it has the potential to form a layer of bone-like
      hydroxyapatite, which is essential for achieving direct bonding to living bone.
      This type of modification allows the cement to show spontaneous hydroxyapatite
      formation on its surface in a simulated body fluid after one day, and there is
      evidence of osteoconduction of the cement in rabbit tibia for periods of more
      than three weeks. However, the influence of the dissolved ions from the modified
      cement has not yet been clarified. Thus, the authors focused on the dissolution
      of the modified PMMA-based bone cement and its tissue response in muscle and bone
      by comparison with the behavior of non-modified PMMA-based bone cement. One week
      after implantation in the latissimus dorsi of a rabbit, the modified PMMA-based
      bone cement showed more inflammatory width than the commercial cement. However,
      four weeks after implantation, the inflammatory width of both cements was
      essentially the same. The osteoconductivity around the modified cement was higher
      than that for the conventional cement after four weeks implantation. These
      results indicate that the initial dissolution of calcium acetate from the
      modified cement to form the hydroxyapatite induced the acute inflammation around
      tissue, but also developed the osteoconductivity. It is suggested that the
      initial inflammation can be effective for inducing osteoconduction through a bone
      healing reaction when the material provides an environment that promotes bone
      formation.

PMID- 18632772
TI  - Protecting axons in multiple sclerosis.
AB  - Typically patients with multiple sclerosis (MS) experience acute episodes of
      neurological dysfunction, which recover followed, at a later stage, by slow and
      insidious accumulation of disability (disease progression). Disease progression
      reflects axon damage and loss within the central nervous system. However, the
      precise mechanism of axon injury in MS is not clear. Inflammation occurring
      during acute relapses undoubtedly causes some degree of acute axon damage, but
      epidemiological data and treatment studies have suggested that inflammation alone
      is not the sole cause of axonopathy. Indeed, there appears to be dissociation
      between inflammation and disease progression once a certain level of clinical
      disability has been reached because immune suppression in patients who have
      established disease progression does not halt the slow decrease of function. The
      slow and insidious loss of neurological function that occurs during the
      progressive phase of the disease implies a degenerative process. Whether axon
      drop-out occurs at these later stages because of previous inflammatory damage to
      axons; because of low grade inflammation causing damage to already vulnerable
      demyelinated axons; because of loss of trophic environment for axons to survive;
      or as part of a completely independent neurodegenerative process is not clear.
      Understanding disease mechanisms involved in the axonopathy of MS allows for the
      development of rational therapies for disease progression.

PMID- 18632773
TI  - Complementary and alternative medicine for multiple sclerosis.
AB  - We analyzed characteristics, motivation, and effectiveness of complementary and
      alternative medicine in a large sample of people with multiple sclerosis. A 53
      item survey was mailed to the members of the German Multiple Sclerosis Society,
      chapter of Baden-Wuerttemberg. Surveys of 1573 patients (48.5 +/- 11.7 years, 74%
      women, duration of illness 18.1 +/- 10.5 years) were analyzed. In comparison with
      conventional medicine, more patients displayed a positive attitude toward
      complementary and alternative medicine (44% vs 38%, P < 0.05), with 70% reporting
      lifetime use of at least one method. Among a wide variety of complementary and
      alternative medicine, diet modification (41%), Omega-3 fatty acids (37%), removal
      of amalgam fillings (28%), vitamins E (28%), B (36%), and C (28%), homeopathy
      (26%), and selenium (24%) were cited most frequently. Most respondents (69%) were
      satisfied with the effects of complementary and alternative medicine. Use of
      complementary and alternative medicine was associated with religiosity,
      functional independence, female sex, white-collar job, and higher education (P <
      0.05). Compared with conventional therapies, complementary and alternative
      medicine rarely showed unwanted side effects (9% vs 59%, P < 0.00001). A total of
      52% stated that the initial consultation with their physician lasted less than 15
      min. To conclude, main reasons for the use of complementary and alternative
      medicine include the high rate of side effects and low levels of satisfaction
      with conventional treatments and brief patients/physicians contacts.

PMID- 18632774
TI  - Canadian treatment optimization recommendations (TOR) as a predictor of disease
      breakthrough in patients with multiple sclerosis treated with interferon beta-1a:
      analysis of the PRISMS study.
AB  - BACKGROUND: Early intervention with an effective disease-modifying drug (DMD)
      offers the best chance of limiting the inflammatory process that contributes to
      irreversible axonal damage correlating with disability in multiple sclerosis
      (MS). It is equally important to ascertain fairly quickly whether patients are
      responding positively to the choice of therapy to allow time for either a
      treatment modification or a switch in treatment, a process we termed "treatment
      optimization". Various treatment optimization recommendations (TOR) have been
      proposed to help decide when a patient taking an MS DMD might be showing a sub
      optimal response. We have applied the clinical scheme proposed by the Canadian
      TOR to the patients involved in the Prevention of Relapses and disability by
      Interferon Subcutaneously in MS 4-year (PRISMS-4) study, who received interferon
      beta-1a treatment for 4 years, with the TOR applied retrospectively at year 1.
      OBJECTIVE: The aim of this investigation was to examine whether these TOR were
      able to predict which patients would go on to develop disease breakthrough
      (defined as any relapses or disease progression), indicative of a sub-optimal
      response over the ensuing 3 years of study and therefore might have benefited
      from a change in treatment. RESULTS: We found 39% of patients receiving therapy
      experienced either a medium or high level of concern of breakthrough after a year
      of treatment, and 89% of these patients went on to develop further breakthrough
      over years 2-4. Although 67% of the 61% of patients having no or low-level
      concern after a year of treatment also experienced further disease breakthrough,
      it was significantly less than the medium or high group. CONCLUSION: This study
      shows that the Canadian TOR may be an important tool for early treatment
      optimization.

PMID- 18632775
TI  - Smoking is a risk factor for early conversion to clinically definite multiple
      sclerosis.
AB  - BACKGROUND: Cigarette smoking increases the risk for development of multiple
      sclerosis and modifies the clinical course of the disease. In this study, we
      determined whether smoking is a risk factor for early conversion to clinically
      definite multiple sclerosis after a clinically isolated syndrome. METHODS: We
      included 129 patients with a clinically isolated syndrome, disseminated white
      matter lesions on brain magnetic resonance imaging, and positive oligoclonal
      bands in the cerebrospinal fluid. The patients' smoking status was obtained at
      the time of the clinically isolated syndrome. RESULTS: During a follow-up time of
      36 months, 75% of smokers but only 51% of non-smokers developed clinically
      definite multiple sclerosis, and smokers had a significantly shorter time
      interval to their first relapse. The hazard ratio for progression to clinically
      definite multiple sclerosis was 1.8 (95% confidence interval, 1.2-2.8) for
      smokers compared with non-smokers (P = 0.008). CONCLUSIONS: Smoking is associated
      with an increased risk for early conversion to clinically definite multiple
      sclerosis after a clinically isolated syndrome, and our results suggest that
      smoking is an independent but modifiable risk factor for disease progression of
      multiple sclerosis. Therefore, it should be considered in the counseling of
      patients with a clinically isolated syndrome.

PMID- 18632776
TI  - Prevalence of sleep problems in individuals with multiple sclerosis.
AB  - BACKGROUND: Sleep disturbance in multiple sclerosis has received little research
      attention despite the potential influence it may have on disease impact.
      OBJECTIVE: To estimate the prevalence of sleep disorders in a large community
      sample of individuals with multiple sclerosis. METHODS: A cross-sectional self
      report survey of 1063 persons with multiple sclerosis. Sleep was assessed using
      the Women's Health Initiative Insomnia Rating Scale and Medical Outcomes Study
      Sleep measure. RESULTS: The prevalence of sleep problems in multiple sclerosis is
      significantly higher than in the general population or other chronic diseases and
      may affect women with multiple sclerosis more than men. CONCLUSION: Sleep
      disturbance should routinely be evaluated in patients with multiple sclerosis and
      new interventions developed.

PMID- 18632777
TI  - Correlation between DJ-1 levels in the cerebrospinal fluid and the progression of
      disabilities in multiple sclerosis patients.
AB  - OBJECTIVES: DJ-1 plays a key role in the anti-oxidative stress function.
      Increasing evidence supports the role of oxidative stress in the pathogenesis of
      multiple sclerosis (MS). The aim of this study was to investigate whether the DJ
      1 levels were increased in patients with MS and to examine its association with
      the progression of MS. METHODS: Quantitative immunoblot assays were performed to
      evaluate the DJ-1 level in serum and cerebrospinal fluid (CSF) collected from
      relapsing-remitting patients with MS (n = 29), disease controls subjects (n =
      14), and healthy subjects (n = 44). RESULTS: No significant difference was
      observed in the serum DJ-1 level among the patients with MS, disease controls,
      and healthy controls. However, the CSF DJ-1 levels were significantly higher in
      the patients with MS than in the disease control subjects (P < 0.0001). A
      significant positive correlation was also found between the CSF DJ-1 levels and
      the Multiple Sclerosis Severity Score (P < 0.005, r = 0.501). CONCLUSIONS: These
      results show that the CSF DJ-1 levels are significantly increased in the CSF of
      patients with MS and that the CSF DJ-1 levels may be associated with the disease
      progression of MS. Therefore, DJ-1 possibly plays an important role in the
      pathogenesis of MS.

PMID- 18632778
TI  - Smoking worsens the prognosis in multiple sclerosis.
AB  - OBJECTIVE: To estimate the effect of smoking on the risk for progression in
      multiple sclerosis (MS). METHODS: Self-reported data were used on smoking habits
      in 122 incident cases with disability assessments made after a median of 6 years
      disease duration. RESULTS: Ever smokers were more likely to have progressive
      disease compared with never smokers (P < 0.01). This was most pronounced in ever
      smokers with early smoking debut (< or = 15 years of age) for whom progressive
      disease was significantly more likely and occurred at an earlier age, compared
      with those with later smoking debut (P < 0.01 for both) or never smokers (P <
      0.01 for both). Earlys moking start also predisposed to a progressive disease
      from onset when compared with never smokers (P = 0.012). A multivariate Cox
      regression analysis of sex, age at disease onset (above vs. under median) and
      smoking (ever vs. never) status showed that cases with late disease onset had
      three times higher risk and ever smokers had twice as high a risk for
      progression. CONCLUSION: Past smoking is associated with a worsened prognosis in
      MS. The negative effect from smoking is most obvious in ever smokers with early
      smoking debut, which also affects MS phenotype significantly.

PMID- 18632779
TI  - The impact of disabilities on quality of life in people with multiple sclerosis.
AB  - OBJECTIVE: People with Multiple Sclerosis (MS) experience lower levels of quality
      of life (QOL) than people from the general population. We examined the relative
      impact of MS-related disabilities on QOL. METHOD: Data were obtained from a
      sample of 530 patients who completed the Multiple Sclerosis Impact Profile
      (MSIP), a disability measure based on the International Classification of
      Functioning, Disabilities and Health (ICF) and two generic health-related QOL
      measures, the Medical Outcome study Short Form Questionnaire (SF-36) and the
      World Health Organization Quality Of Life-BREF (WHOQOL-BREF). The impact of
      disabilities on QOL was estimated using hierarchical multiple regression analyses
      after controlling for the clinical course of MS. RESULTS: Disabilities
      contributed to a unique and substantial extent to QOL variance. "Impairments in
      mental functions" was the most important QOL predictor. "Fatigue" showed the
      highest prevalence and severity scores, while the impact on QOL was limited. The
      estimated impact on QOL appeared to be dependent on the applied QOL measure: the
      WHOQOL-BREF was sensitive to disabilities related to all four ICF components,
      while the SF-36 was only sensitive to disabilities belonging to the 'body
      functions' and 'activities' components. CONCLUSION: Treatment programmes should
      target impairments in cognitive functioning, emotional functioning and sleep.
      Interventions are best evaluated using the WHOQOL-BREF.

PMID- 18632780
TI  - Neuropsychological dysfunction, depression, physical disability, and coping
      processes in families with a parent affected by multiple sclerosis.
AB  - BACKGROUND: Families with a parent suffering from multiple sclerosis (MS) must
      cope with the unpredictable course of the disease. Most studies analyzing factors
      that influence coping abilities in families with a member affected with MS used
      questionnaires to assess this ability. METHODS: On the contrary, the present
      study used a semi-structured psychiatric interview and used the resulting
      information to calculate a general measure of coping ability (coping index [CI]).
      We administered this interview to 44 MS patients, their partners and offspring
      and conducted a neuropsychological and physical evaluation of the patients to
      determine the impact of physical disability, cognitive dysfunction, and
      depression on the process of coping by the patient, the healthy partner, and
      children. RESULTS: The CI of patients was best predicted by measures of their
      depressive symptoms, divided attention, and estimated verbal intelligence. None
      of the patient variables predicted the CI of healthy partners or their offspring.
      We found an association between the CI of the healthy partner and the children.
      CONCLUSIONS: These findings suggest that MS patients' emotional and
      neuropsychological functions are associated with their ability to cope with the
      disease. These should be carefully assessed at the beginning of treatment so that
      those factors known to negatively influence patient coping are targeted in the
      treatment plan if necessary. Comprehensive care of a patient with MS should
      include support of coping abilities of the family members.

PMID- 18632781
TI  - Survival and cause of death in multiple sclerosis: results from a 50-year follow
      up in Western Norway.
AB  - BACKGROUND: Survival time among patients with multiple sclerosis (MS) has varied
      considerably according to previous reports. OBJECTIVES: Survival and cause of
      death were analyzed among all patients with MS (878) with onset of MS in
      Hordaland County, Western Norway during 1953-2003, of whom 198 were dead at
      follow-up on January 1, 2005. METHODS: Standardized mortality ratios (SMRs) and
      relative mortality ratios (RMRs) were calculated based on observed mortality in
      MS and expected mortality. RESULTS: Median survival from onset was 41 years
      versus 49 years in the corresponding population, and mortality (SMR) was 2.7-fold
      increased in MS. The median survival was 43 years among women and 36 years among
      men, but women had higher relative mortality, when compared with the
      corresponding population, than men (RMR = 1.40). The median survival time was 45
      years among young-onset patients (21-30 years) and 23 years among older-onset
      patients (51-60 years), but young-onset patients had higher relative mortality
      than older-onset patients, as shown by a significant reduction by 10-year
      interval of age at onset (RMR = 0.65). Median survival from onset was longer (43
      years) among relapsing-remitting MS than primary progressive MS ([PPMS]; 49
      years), and the relative mortality was higher in the PPMS group, (RMR = 1.55).
      According to death certificates, 57% died from MS. CONCLUSION: Female patients
      and patients with young onset had longer median time to death but higher relative
      risk of dying compared with the corresponding population. PPMS had both shorter
      median time to death from onset and a higher relative risk of dying.

PMID- 18632782
TI  - Magnetic resonance imaging measures of brain and spinal cord atrophy correlate
      with clinical impairment in secondary progressive multiple sclerosis.
AB  - BACKGROUND: Neuroaxonal loss is a pathological substrate of disability in
      progressive multiple sclerosis (MS) and can be estimated in vivo by measuring
      tissue atrophy on magnetic resonance imaging (MRI). While there is some evidence
      that brain atrophy correlates better with disability than T2 lesion load in
      secondary progressive MS, the clinical relevance of atrophy within specific
      regions of the central nervous system requires further evaluation. METHODS:
      Clinical and MRI examinations were performed in 117 subjects with secondary
      progressive MS. MRI analysis included measures of normalized brain volume (NBV),
      normalized grey matter (NGMV) and white matter volume (NWMV), central cerebral
      volume (CCV), spinal cord cross-sectional area (SCCA), and brain T2 and T1 lesion
      volume. Clinical assessments included the expanded disability status scale (EDSS)
      and MS functional composite (MSFC). RESULTS: All MRI measures correlated
      significantly with the MSFC score, with the strongest correlation being for the
      NBV (r = 0.47; P < 0.001). NBV and SCCA were the only significant independent
      predictors of the MSFC score in a stepwise regression model containing all the
      MRI measures, and SCCA was the only MRI measure to show a significant association
      with the EDSS. While NGMV had stronger correlations with the clinical variables
      than NWMV, NBV was more correlated with clinical impairment than either measure.
      CONCLUSIONS: This data suggests that measures of atrophy, particularly of the
      whole brain and spinal cord, are relevant and useful disease markers in secondary
      progressive MS.

PMID- 18632783
TI  - The impact of sexual dysfunction on the quality of life measured by MSQoL-54 in
      patients with multiple sclerosis.
AB  - OBJECTIVE: Sexual dysfunction (SD) is a common but often overlooked symptom in
      multiple sclerosis (MS). The aim of this study was to estimate the frequency,
      type, and intensity of SD in our patients with MS and to investigate its
      influence on all the domains of quality of life. METHODS: The study population
      comprised a cohort of 109 patients with MS (McDonald's criteria, 2001). SD was
      quantified by a Szasz sexual functioning scale. Health-related quality of life
      was measured by a disease-specific instrument MSQoL-54 (Serbian version).
      RESULTS: The presence of at least one symptom of SD was found in about 84% of the
      men and in 85% of the women. The main complaints in women were reduced libido,
      difficulties in achieving orgasm, and decreased vaginal lubrication; in men, the
      main complaints were reduced libido, incomplete erections, and premature
      ejaculation. In women, statistically significant negative correlations between
      the presence and level of SD and quality of life domains were reached for all
      subscales (P < 0.01), except for the Pain subscale (P = 0.112). In men, negative
      correlations were also observed for all domains, but they were statistically
      significant for physical health, physical role limitations, social function,
      health distress, sexual function, and sexual function satisfaction (P < 0.01). We
      found that the presence of all the analyzed types of sexual problems
      statistically significantly lowered scores on the sexual function and the sexual
      function satisfaction subscales in both men and women (P < 0.01). The most
      prominent impact on both domains was observed for the total loss of erection in
      men and for anorgasmia in women. CONCLUSIONS: Our results reveal that frequent
      occurrence of SD in MS patients prominently affects all aspects of their quality
      of life.

PMID- 18632784
TI  - A case of Fabry disease with central nervous system (CNS) demyelinating lesions:
      a double trouble?
AB  - We present the case of a 36-year-old woman affected with Fabry disease (FD), with
      neuroradiologic and laboratory tests suggestive of a coexistent inflammatory
      demyelinating disease. Since the age of 23, she presented recurrent neurologic
      deficits, such as right limb paresthesias, diplopia, and right leg weakness.
      Magnetic resonance imaging revealed multiple demyelinating lesions in
      periventricular areas, corpus callosum, and spinal cord. Cerebrospinal fluid
      analysis showed the presence of oligoclonal bands, while visual-evoked potentials
      were delayed with preserved morphology. FD is usually considered as a
      differential diagnosis of multiple sclerosis, but we think that the best
      explanation of all pathological features in this case is the coexistence of the
      two diseases.

PMID- 18632785
TI  - Setting the agenda for multiple sclerosis rehabilitation research.
AB  - BACKGROUND: Recognizing the need for more evidence-based multiple sclerosis (MS)
      rehabilitation, in the mid-2000s several initiatives were undertaken to explore
      why there had been a paucity of such research and to determine strategies to
      reverse this pattern. EXPERT-OPINION-PAPER: In 2004 the National Multiple
      Sclerosis Society (NMSS) convened an expert opinion panel, reviewed evidence
      based MS rehabilitation research, and published the paper on the web. It was
      concluded that much of the MS rehabilitation carried out was based on experience,
      with little research backing it up. INCREASING THE QUALITY AND QUANTITY OF MS
      REHABILITATION RESEARCH: Largely as a result of the conclusions of the Expert
      Opinion-Paper, the NMSS convened a conference of a large number of MS and
      rehabilitation experts in New York in May, 2005. This conference made many
      recommendations of ways to increase the quantity and quality of MS research.
      STATE OF THE SCIENCE CONFERENCE: In September, 2006, a follow-up conference was
      held in Washington, D.C... This conference, primarily sponsored by the University
      of Washington Multiple Sclerosis Rehabilitation Research and Training Center (MS
      RRTC), focused on some of the under-studied "hidden" disabilities present in
      persons with MS. This paper discusses the details and recommendations of these
      latter two conferences.

PMID- 18632786
TI  - No evidence that polymorphisms of the vanishing white matter disease genes are
      risk factors in multiple sclerosis.
AB  - Febrile infections are known to cause exacerbations in the white matter disorders
      'vanishing white matter' (VWM) and multiple sclerosis (MS). We hypothesized that
      polymorphisms in EIF2B1-5, the genes involved in VWM, might be risk factors for
      the development of MS or temperature sensitivity in patients with MS. We found no
      difference in the frequencies of 15 EIF2B1-5 variants between patients with MS
      and healthy controls, and none of the variants showed significant deviation of
      the Hardy-Weinberg equilibrium. Furthermore, sequencing data of EIF2B1-5 in 20
      patients with MS and measurement of the activity of eIF2B complex in patient
      derived lymphoblasts did not support our hypothesis.

PMID- 18632787
TI  - Mothers', fathers', and children's perceptions of parental diabetes
      responsibility in adolescence: examining the roles of age, pubertal status, and
      efficacy.
AB  - OBJECTIVES: To examine how perceptions of parental responsibility for diabetes
      management are associated with age, pubertal status, adolescents' self-efficacy,
      and parental perceptions of adolescents' efficacy, and if parental responsibility
      is associated with better metabolic control as a function of adolescents' self
      efficacy and parental perceptions of adolescents' efficacy. METHODS:
      Questionnaires assessing parental responsibility, pubertal status, adolescents'
      self-efficacy, and parental perceptions of adolescents' efficacy were given to
      185 adolescents with type 1 diabetes, 185 mothers, and 145 fathers. RESULTS:
      Greater parental responsibility was negatively associated with age, perceptions
      of pubertal status, and efficacy for all reporters. Interactions between parental
      responsibility and parental perceptions of adolescents' efficacy indicated that
      parental responsibility was associated with better metabolic control when
      adolescents were perceived to have lower efficacy. CONCLUSIONS: Adolescents' and
      parents' perceptions of parental responsibility are related to multiple factors.
      Metabolic control is best when high parental responsibility is maintained among
      adolescents with lower efficacy.

PMID- 18632788
TI  - Contralateral hyperalgesia and allodynia following intradermal capsaicin
      injection in man.
AB  - OBJECTIVES: Contralateral responses to unilateral stimuli have been well
      described in animal models. These range from central sensitization to peripheral
      inflammatory responses. Our aim was to test for contralateral responses following
      unilateral intradermal capsaicin injection in man. METHODS: Three groups were
      investigated. A healthy volunteer group (1) was injected with capsaicin into the
      volar aspect of one forearm. A group of patients with RA (2) was also injected
      with capsaicin. A control group of healthy volunteers (3) was not injected with
      capsaicin. All groups were tested for hyperalgesia and allodynia every 10 min for
      1 h following the injection using quantitative sensory testing. RESULTS: A total
      of 9/14 healthy volunteers (Group 1) and 10/14 patients with RA (Group 2)
      demonstrated contralateral sensitization that subsided within 1 h following
      intradermal capsaicin injection. A total of 2/23 control subjects (Group 3)
      demonstrated positive responses with the monofilaments. The frequency of the
      contralateral responses in the experimental groups compared with the control
      group is significant (P < 0.05). The peak hyperalgesia was relatively delayed
      contralaterally compared with the ipsilateral side (35 min vs 15 min). The area
      of sensitization, where present, was reduced compared with the ipsilateral side
      (5-50%). CONCLUSIONS: This is the first demonstration of a contralateral response
      following a unilateral stimulus in man. Bilateral neural pathways mediating
      contralateral responses may have a role in the pathophysiology of chronically
      painful or inflammatory diseases and a confounding influence on using the
      contralateral limb as a control experimentally. We did not find that a systemic
      inflammatory disease sensitized for this phenomenon.

PMID- 18632789
TI  - Development of a web-based register for the Dutch national study on biologicals
      in JIA: www.ABC-register.nl.
AB  - OBJECTIVES: Most clinical studies use paper case record forms (CRFs) to collect
      data. In the Dutch multi-centre observational study on biologicals we encountered
      several disadvantages of using the paper CRFs. These are delay in data
      collection, lack of overview in collected data and difficulties in obtaining up
      to-date interim reports. Therefore, we wanted to create a more effective method
      of data collection compared with CRFs on paper in a multi-centre study. METHODS:
      We designed a web-based register with the intention to make it easy to use for
      participating physicians and at the same time accurate and up-to-date. Security
      demands were taken into account to secure the safety of the patient data.
      RESULTS: The web-based register was tested with data from 161 juvenile idiopathic
      arthritis patients from nine different centres. Internal validity was obtained
      and user-friendliness guaranteed. To secure the completeness of the data
      automatically generated e-mail alerts were implemented into the web-based
      register. More transparency of data was achieved by including the option to
      automatically generate interim reports of data in the web-based register. The
      safety was tested and approved. CONCLUSIONS: By digitalizing the CRF we achieved
      our aim to provide easy, rapid and safe access to the database and contributed to
      a new way of data collection. Although the web-based register was designed for
      the current multi-centre observational study, this type of instrument can also be
      applied to other types of studies. We expect that especially collaborative study
      groups will find it an efficient tool to collect data.

PMID- 18632790
TI  - Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses.
AB  - Heme oxygenases (HO-1, HO-2) catalyze conversion of heme to iron, carbon monoxide
      (CO), and biliverdin/bilirubin. We studied the effects of renal HO-1 induction on
      afferent arteriole (Aff-Art) autoregulatory responses to increases in renal
      perfusion pressure (RPP). Rats were treated with hemin and SnCl2 to induce HO-1,
      and Aff-Art autoregulatory responses were evaluated using the rat blood-perfused
      juxtamedullary nephron preparation. Renal HO-1 expression was significantly
      increased in hemin- and SnCl2-treated rats, while HO-2 was not altered. Aff-Art
      autoregulatory constrictor responses to increases in RPP from 100 to 150 mmHg
      were attenuated in hemin- and SnCl2-treated rats compared with control rats
      (+1.1+/-3.3, n=9 and +4.4+/-5.3, n=9 vs. -14.2+/-1.5%, n=10, respectively)
      (P<0.05). Acute HO inhibition with chromium mesoporphyrin (CrMP; 15 micromol/l)
      restored Aff-Art autoregulatory responses in hemin- and SnCl2-treated rats.
      Superfusing Aff-Arts from control rats with 100 micromol/l biliverdin did not
      alter autoregulatory responses; however, superfusion with 1 mmol/l CO
      significantly attenuated autoregulatory responses to increases in RPP from 100 to
      150 mmHg (+3.3+/-5.4 vs. -16.6+/-3.8%, n=6) (P<0.05). Acute soluble guanylate
      cyclase inhibition with 10 micromol/l ODQ restored Aff-Art autoregulatory
      responses in hemin-treated rats. Immunohistochemistry shows HO-2 to be expressed
      mainly in epithelial cells with weak staining in proximal tubules, interlobular
      arteries, and Aff-Arts. In hemin- and SnCl2-treated rats, HO-1 was induced in
      tubular epithelial cells but not interlobular arteries and Aff-Arts. We conclude
      that induction of renal HO-1 attenuates Aff-Art constrictor responses to
      increases in RPP via increasing CO production from tubular epithelial cells,
      suggesting that an augmented HO system in pathophysiological conditions modulates
      renal autoregulation.

PMID- 18632791
TI  - Modulation of bladder function by prostaglandin EP3 receptors in the central
      nervous system.
AB  - Prostaglandin EP3 receptors in the central nervous system (CNS) may exert an
      excitatory effect on urinary bladder function via modulation of bladder afferent
      pathways. We have studied this action, using two EP3 antagonists, (2E)-3-{1-[(2,4
      dichlorophenyl)methyl]-5-fluoro-3-methyl-1H-indol-7-yl}-N-[(4,5-dichloro-2
      thienyl)sulfonyl]-2-propenamide (DG041) and (2E)-N-{[5-bromo-2-(methyloxy)phenyl]
      sulfonyl}-3-[2-(2-naphthalenylmethyl)phenyl]-2-propenamide (CM9). DG041 and CM9
      were proven to be selective EP3 antagonists with radioligand binding and
      functional fluorescent imaging plate reader (FLIPR) assays. Their effects on
      volume-induced rhythmic bladder contraction and the visceromotor reflex (VMR)
      response to urinary bladder distension (UBD) were evaluated in female rats after
      intrathecal or intracerebroventricular administration. Both DG041 and CM9 showed
      a high affinity for EP3 receptors at subnanomolar concentrations without
      significant selectivity for any splice variants. At the human EP3C receptor, both
      inhibited calcium influx produced by the nonselective agonist PGE2. After
      intrathecal or intracerebroventricular administration both CM9 and DG041 dose
      dependently reduced the frequency, but not the amplitude, of the bladder rhythmic
      contraction. With intrathecal administration DG041 and CM9 produced a long
      lasting and robust inhibition on the VMR response to UBD, whereas with
      intracerebroventricular injection both compounds elicited only a transient
      reduction of the VMR response to bladder distension. These data support the
      concept that EP3 receptors are involved in bladder micturition at supraspinal and
      spinal centers and in bladder nociception at the spinal cord. A centrally acting
      EP3 receptor antagonist may be useful in the control of detrusor overactivity
      and/or pain associated with bladder disorders.

PMID- 18632792
TI  - Upregulation of vascular endothelial growth factor isoform VEGF-164 and receptors
      (VEGFR-2, Npn-1, and Npn-2) in rats with cyclophosphamide-induced cystitis.
AB  - Regulation of the VEGF-VEGF receptor system was examined in the urinary bladder
      after acute (2-48 h) and chronic (10 days) cyclophosphamide (CYP)-induced
      cystitis. ELISAs demonstrated significant (P < or = 0.01) upregulation of VEGF in
      whole urinary bladder with acute and chronic CYP-induced cystitis; however, the
      magnitude of increase was greater after acute (2-4 h) cystitis.
      Immunohistochemistry for VEGF immunoreactivity revealed a significant (P < or =
      0.05) increase in VEGF immunoreactivity in the urothelium, suburothelial
      vasculature, and detrusor smooth muscle with acute (4 and 48 h) CYP treatment. RT
      PCR identified the isoform VEGF-164, the VEGF receptor VEGFR-2, and the VEGF co
      receptors neuropilin (Npn)-1 and Npn-2 in the urinary bladder. Quantitative PCR
      demonstrated upregulation of VEGF-164 transcript with acute and chronic CYP
      induced cystitis, but VEGFR-2, Npn-1, and Npn-2 transcripts were upregulated (P <
      or = 0.01) in whole bladder only with chronic CYP-induced cystitis. Additional
      studies demonstrated regulation of VEGF transcript expression in the urinary
      bladder by nerve growth factor (NGF) in a novel line of NGF-overexpressing mice.
      These studies demonstrated that urinary bladder inflammation and NGF regulate the
      VEGF-VEGF receptor system in the urinary bladder. Functional role(s) for the VEGF
      VEGF receptor system in urinary bladder inflammation remain to be determined.

PMID- 18632793
TI  - Interstitial cells of Cajal in the urethra are cGMP-mediated targets of nitrergic
      neurotransmission.
AB  - While interstitial cells of Cajal (ICC) in the urethra respond to nitric oxide
      (NO) donors by increasing cGMP, it remains unclear whether urethral ICC are
      functionally innervated by nitrergic nerves. We have addressed this issue in the
      rat and sheep urethra, where cGMP production and relaxation were compared in
      preparations subjected to electrical field stimulation (EFS; 2 Hz, 4 min) of
      nitrergic nerves or to exogenous S-nitroso-L-cysteine (SNC; 0.1 mM, 4 min). Upon
      EFS, cGMP immunoreactivity (cGMP-ir) was observed in both smooth muscle cells
      (SMC) and in spindle-shaped cells that contained c-kit and vimentin, features of
      ICC. Similarly, cGMP-ir was preferentially, but inconsistently, found in ICC of
      the outer muscle layer on exposure to SNC. We found separate functional groups of
      ICC within the urethra. Thus only ICC present in the muscle layers (ICC-M) but
      not those in the serosa (ICC-SR) and lamina propia (ICC-LP) seem to be
      specifically influenced by activation of neuronal NO synthase (nNOS). Thus the
      increase in cGMP-ir in the ICC-M induced by EFS was prevented by Nomega-nitro-L
      arginine and ODQ. Urethral ICC did not express nNOS, although they were closely
      associated with nitrergic nerves. cGMP-ir was also present in the urothelium (in
      the rat but not in the sheep) and the vascular endothelium but not in neural
      structures, such as the nerve trunks and nerve terminals. Together, these results
      suggest a model of parallel innervation in which both SMC and ICC-M are effectors
      of nerve-released NO in the urethra.

PMID- 18632794
TI  - Human H+ATPase a4 subunit mutations causing renal tubular acidosis reveal a role
      for interaction with phosphofructokinase-1.
AB  - The vacuolar-type ATPase (H+ATPase) is a ubiquitously expressed multisubunit pump
      whose regulation is poorly understood. Its membrane-integral a-subunit is
      involved in proton translocation and in humans has four forms, a1-a4. This study
      investigated two naturally occurring point mutations in a4's COOH terminus that
      cause recessive distal renal tubular acidosis (dRTA), R807Q and G820R. Both lie
      within a domain that binds the glycolytic enzyme phosphofructokinase-1 (PFK-1).
      We recreated these disease mutations in yeast to investigate effects on protein
      expression, H+ATPase assembly, targeting and activity, and performed in vitro PFK
      1 binding and activity studies of mammalian proteins. Mammalian studies revealed
      complete loss of binding between the COOH terminus of a4 containing the G-to-R
      mutant and PFK-1, without affecting PFK-1's catalytic activity. In yeast
      expression studies, protein levels, H+ATPase assembly, and targeting of this
      mutant were all preserved. However, severe (78%) loss of proton transport but
      less decrease in ATPase activity (36%) were observed in mutant vacuoles,
      suggesting a requirement for the a-subunit/PFK-1 binding to couple these two
      functions. This role for PFK in H+ATPase function was supported by similar
      functional losses and uncoupling ratio between the two proton pump domains
      observed in vacuoles from a PFK-null strain, which was also unable to grow at
      alkaline pH. In contrast, the R-to-Q mutation dramatically reduced a-subunit
      production, abolishing H+ATPase function completely. Thus in the context of dRTA,
      stability and function of the metabolon composed of H+ATPase and glycolytic
      components can be compromised by either loss of required PFK-1 binding (G820R) or
      loss of pump protein (R807Q).

PMID- 18632795
TI  - Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via
      spinal GABAergic inhibition in anesthetized rats.
AB  - The impact of acute anal stretch on the pelvic-urethra reflex potentiation was
      examined in urethane-anesthetized rats by recording the external urethra
      sphincter electromyogram activity evoked by the pelvic afferent stimulation. Test
      stimulation (1 stimulation/30 s) evoked a baseline reflex activity with a single
      action potential that was abolished by gallamine (5 mg/kg iv). On the other hand,
      the repetitive stimulation (1 stimulation/1 s) induced spinal reflex potentiation
      (SRP) that was attenuated by intrathecal 6-cyano-7-nitroquinoxaline-2,4-dione (a
      glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionat receptor
      antagonist, 100 microM, 10 microl) and d-2-amino-5-phosphonovalerate [a
      glutamatergic N-methyl-D-aspartate (NMDA) antagonist, 100 microM, 10 microl].
      Acute anal stretch using a mosquito clamp with a distance of 4 mm exhibited no
      effect, whereas distances of 8 mm attenuated and 12 mm abolished the repetitive
      stimulation-induced SRP. Intrathecal NMDA (100 microM, 10 microl) reversed the
      abolition on SRP caused by anal stretch. On the other hand, pretreated
      bicuculline [gamma-aminobutyric acid (GABA) A receptor antagonist, 100 microM, 10
      microl] but not hydroxysaclofen (GABAB receptor antagonist) counteracted the
      abolition on the repetitive stimulation-induced SRP caused by the anal stretch.
      All of the results suggested that anal stretch may be used as an adjunct to
      assist voiding dysfunction in patients with overactive urethra sphincter and that
      GABAergic neurotransmission is important in the neural mechanisms underlying
      external urethra sphincter activity inhibited by anal stretch.

PMID- 18632796
TI  - Increased dietary NaCl induces renal medullary PGE2 production and natriuresis
      via the EP2 receptor.
AB  - A high-NaCl diet induces renal medullary cyclooxygenase (COX)2 expression, and
      selective intramedullary infusion of a COX2 inhibitor increases blood pressure in
      rats on a high-salt diet. The present study characterized the specific prostanoid
      contributing to the antihypertensive effect of COX2. C57BL/6J mice placed on a
      high-NaCl diet exhibited increased medullary COX2 and microsomal prostaglandin E
      synthase1 (mPGES1) expression as determined by immunoblot and real-time PCR.
      Cytosolic prostaglandin E synthase and prostacyclin synthase were not induced by
      the high-salt diet. Immunofluorescence showed mPGES1 in collecting ducts and
      interstitial cells. High salt increased renal medullary PGE(2) as determined by
      gas chromatography/negative ion chemical ionization mass spectrometry. The effect
      of direct intramedullary PGE(2) infusion was examined in anesthetized
      uninephrectomized mice. Intramedullary PGE(2) infusion (10 ng/h) increased urine
      volume (from 3.3 +/- 0.6 to 9.5 +/- 1.6 mul/min) and urine sodium excretion (0.11
      +/- 0.02 to 0.32 +/- 0.05 mueq/min). To determine which E-prostanoid (EP)
      receptor(s) mediated PGE(2)- dependent natriuresis, EP-selective prostanoids were
      infused. The EP(2) agonist butaprost produced natriuresis (from 0.06 +/- 0.02 to
      0.32 +/- 0.05 mueq/min). The natriuretic effect of intramedullary PGE(2) or
      butaprost was abolished in EP2-deficient mice, which exhibit NaCl-dependent
      hypertension. In conclusion, a high-salt diet increases renal medullary COX2 and
      mPGES1 expression, and increases renal medullary PGE(2) synthesis. Renal
      medullary PGE(2) promotes renal sodium excretion via the EP2 receptor, thereby
      maintaining normotension in the setting of high salt intake.

PMID- 18632797
TI  - Blockade of renal medullary bradykinin B2 receptors increases tubular sodium
      reabsorption in rats fed a normal-salt diet.
AB  - The present study was performed to test the hypothesis that under normal
      physiological conditions and/or during augmentation of kinin levels, intrarenal
      kinins act on medullary bradykinin B(2) (BKB(2)) receptors to acutely increase
      papillary blood flow (PBF) and therefore Na(+) excretion. We determined the
      effect of acute inner medullary interstitial (IMI) BKB(2) receptor blockade on
      renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or
      a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied.
      Baseline renal hemodynamic and excretory function were determined during IMI
      infusion of 0.9% NaCl into the left kidney. The infusion was then either changed
      to HOE-140 (100 microg.kg(-1).h(-1), treated group) or maintained with 0.9% NaCl
      (time control group), and the parameters were again determined. In rats fed a
      normal-salt diet, HOE-140 infusion decreased left kidney Na(+) excretion (urinary
      Na(+) extraction rate) and fractional Na(+) excretion by 40 +/- 5% and 40 +/- 4%,
      respectively (P < 0.01), but did not alter glomerular filtration rate, inner
      medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet,
      HOE-140 infusion did not alter renal regional hemodynamics or excretory function.
      We conclude that in rats fed a normal-salt diet, kinins act tonically via
      medullary BKB(2) receptors to increase Na(+) excretion independent of changes in
      inner medullary blood flow.

PMID- 18632798
TI  - Dysregulated human renin expression in transgenic mice carrying truncated genomic
      constructs: evidence supporting the presence of insulators at the renin locus.
AB  - We previously generated transgenic mice carrying a large P1 artificial chromosome
      (PAC160) encompassing a 160-kb segment containing the human renin gene, two
      upstream genes, and one downstream gene. We also previously generated mutant
      PAC160 constructs lacking the distal enhancer and concluded it is required to
      maintain baseline expression of human renin, but is not required for tissue
      specific, cell-specific, and regulated expression of renin in vivo. We now report
      two additional transgenic lines carrying random truncations of PAC160 upstream of
      the renin gene. Southern and PCR mapping studies indicate that the truncation
      break points in the two lines are located approximately 10.4 and 2.5 kb upstream
      of the renin gene causing a deletion of all DNA upstream of the break. We tested
      the hypothesis that large-scale deletion of DNA upstream of the human renin gene
      including the enhancer would cause dysregulation of human renin expression.
      Phenotypically, these truncations cause a severe dysregulation of human renin
      expression, but remarkably, a preservation of the normal tissue-specific
      expression of the human ethanolamine kinase 2 (ETNK2) gene which lies immediately
      downstream of renin. Several functional binding sites for CTCF, a mammalian
      insulator protein, were identified in and around the renin and ETNK2 loci by gel
      shift and chromatin immunoprecipitation. We conclude that there are sequences in
      and around the renin and ETNK2 loci which act as boundaries between neighboring
      genes which insulate them from each other. The study illustrates the value of
      taking a much wider genomic perspective when studying mechanisms regulating gene
      expression.

PMID- 18632799
TI  - Modulation of bladder myofibroblast activity: implications for bladder function.
AB  - Bladder suburothelial myofibroblasts may modulate both sensory responses from the
      bladder wall and spontaneous activity. This study aimed to characterize further
      these cells in their response to exogenous agents implicated in mediating the
      above activity. Detrusor strips, with or without mucosa, and isolated
      suburothelial myofibroblasts were prepared from guinea pig bladders. Isometric
      tension, intracellular Ca(2+), and membrane current were recorded. Cell pairs
      were formed by pushing two cells together. Tension, intracellular Ca(2+), and
      membrane potential were also recorded from bladder sheets using normal or spinal
      cord-transected (SCT) rats. Spontaneous contractions were greater in detrusor
      strips with an intact mucosa and were augmented by 10 muM UTP. ATP, UTP, or
      reduced extracellular pH elicited Ca(2+) transients and inward currents (E(rev) 
      30 mV) in isolated cells. Capsaicin (5-30 muM) reduced membrane current (37 +/-
      12% of control) with minor effects on Ca(2+) transients: sodium nitroprusside
      reduced membrane currents (40 +/- 21% of control). Cell pair formation, without
      an increase in cell capacitance, augmented ATP and pH responses (180 +/- 58% of
      control) and reduced the threshold to ATP and acidosis. Glivec (20-50 muM)
      reversibly blocked the augmentation and also reduced spontaneous activity in
      bladder sheets from SCT, but not normal, rats. Glivec also disrupted the spread
      of Ca(2+) waves in SCT sheets, generating patterns similar to normal bladders.
      Suburothelial myofibroblasts respond to exogenous agents implicated in modulating
      bladder sensory responses; responses augmented by physical intercellular contact.
      The action of glivec and its selective suppression of spontaneous activity in SCT
      rats identifies a possible pathway to attenuate bladder overactivity.

PMID- 18632800
TI  - TRPV1 mediates the uterine capsaicin-induced NMDA NR2B-dependent cross-organ
      reflex sensitization in anesthetized rats.
AB  - Spinal cord-mediated cross-organ sensitization between the uterus and the lower
      urinary tract may underlie the high concurrence of obstetrical/gynecological
      inflammation and chronic pelvic pain syndrome characterized by urogenital pain.
      However, the neural pathway and the neurotransmitters involved are still unknown.
      We tested the hypothesis that the excitation of capsaicin-sensitive primary
      afferent fibers arising from the uterus through the stimulation of transient
      receptor potential vanilloid 1 (TRPV1) induces cross-organ sensitization on the
      pelvic-urethra reflex activity. Capsaicin (1-1,000 microM, 0.05 ml) was instilled
      into the uterus to induce cross-organ reflex sensitization. Activation of
      capsaicin-sensitive primary afferent fibers by capsaicin instillation into the
      uterine horn sensitized the pelvic-urethra reflex activity that was reversed by
      an intrauterine pretreatment with capsaizepine, a TRPV1-selective antagonist.
      Intrathecal injection of AP5, a glutamatergic N-methyl-D-aspartate (NMDA)
      antagonist, and Co-101244, an NMDA NR2B-selective antagonist, both abolished the
      cross-organ reflex sensitization caused by capsaicin instillation. These results
      demonstrated that TRPV1 plays a crucial role in contributing to the capsaicin
      sensitive primary afferent fibers mediating the glutamatergic NMDA-dependent
      cross-organ sensitization between the uterus and the lower urinary tract when
      there is a tissue injury.

PMID- 18632801
TI  - Role of NF-kappaB and PI 3-kinase/Akt in TNF-alpha-induced cytotoxicity in
      microvascular endothelial cells.
AB  - The interaction of tumor necrosis factor (TNF)-alpha with the endothelium is a
      pivotal factor during endotoxemia. Inflammatory conditions are characterized by
      the activation of the transcription factor NF-kappaB and the expression of
      inflammatory mediators. Previous reports indicate that inhibition of NF-kappaB
      activation during sepsis may be beneficial to the microvasculature. In addition,
      the phosphatidylinositol-3-kinase/Akt signaling pathway (PI3-kinase/Akt) has been
      shown to be cytoprotective. In this study, we examined the effect of inhibition
      of NF-kappaB and PI3-kinase/Akt on cell viability, cytokine production, inducible
      nitric oxide synthase (iNOS) expression, and nitric oxide (NO) generation by TNF
      alpha-treated cultured microvascular endothelial cells. TNF-alpha induced
      significant cytotoxicity and was associated with increased inflammatory cytokines
      and NO and increased expression of iNOS. The NF-kappaB inhibitor, pyrrolidine
      dithiocarbamate (PDTC), prevented these increases and significantly attenuated
      the TNF-alpha-induced cytotoxicity. TNF-alpha also caused PI3-kinase/Akt
      activation, which was further increased by PDTC and prevented by the PI3-kinase
      inhibitor, LY294002. Inhibition of PI3-kinase/Akt also significantly potentiated
      TNF-alpha-mediated cytotoxicity. LY294002 treatment resulted in the appearance of
      increased apoptosis, compatible with the known anti-apoptotic properties of PI3
      kinase/Akt. The present results therefore demonstrate a cytotoxic effect of TNF
      alpha in microvascular endothelial cells which can be attenuated by NF-kappaB
      inhibition. In addition, PI3-kinase/Akt activation during TNF-alpha exposure may
      represent a compensatory anti-necrotic and anti-apoptotic pathway. The
      cytoprotective effects of NF-kappaB inhibition and PI3-kinase/Akt activation may
      have potential implications in the treatment of endotoxemia and septic shock.

PMID- 18632802
TI  - Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface
      expression by deubiquitylating and stabilizing sorting nexin 3.
AB  - Adjustment of Na+ balance in extracellular fluids is achieved by regulated Na+
      transport involving the amiloride-sensitive epithelial Na+ channel (ENaC) in the
      distal nephron. In this context, ENaC is controlled by a number of hormones,
      including vasopressin, which promotes rapid translocation of water and Na+
      channels to the plasma membrane and long-term effects on transcription of
      vasopressin-induced and -reduced transcripts. We have identified a mRNA encoding
      the deubiquitylating enzyme ubiquitin-specific protease 10 (Usp10), whose
      expression is increased by vasopressin at both the mRNA and the protein level.
      Coexpression of Usp10 in ENaC-transfected HEK-293 cells causes a more than
      fivefold increase in amiloride-sensitive Na+ currents, as measured by whole cell
      patch clamping. This is accompanied by a three- to fourfold increase in surface
      expression of alpha- and gamma-ENaC, as shown by cell surface biotinylation
      experiments. Although ENaC is well known to be regulated by its direct
      ubiquitylation, Usp10 does not affect the ubiquitylation level of ENaC,
      suggesting an indirect effect. A two-hybrid screen identified sorting nexin 3
      (SNX3) as a novel substrate of Usp10. We show that it is a ubiquitylated protein
      that is degraded by the proteasome; interaction with Usp10 leads to its
      deubiquitylation and stabilization. When coexpressed with ENaC, SNX3 increases
      the channel's cell surface expression, similarly to Usp10. In mCCD(cl1) cells,
      vasopressin increases SNX3 protein but not mRNA, supporting the idea that the
      vasopressin-induced Usp10 deubiquitylates and stabilizes endogenous SNX3 and
      consequently promotes cell surface expression of ENaC.

PMID- 18632803
TI  - Plasma membrane-associated sialidase as a crucial regulator of transmembrane
      signalling.
AB  - Mammalian sialidases, glycosidases responsible for the removal of sialic acids
      from glycoproteins and glycolipids, has been implicated to participate in many
      biological processes as well as in lysosomal catabolism. Among those forms
      identified to date, plasma membrane-associated sialidase, Neu3, is a key enzyme
      in degradation of gangliosides, for which it exhibits a special substrate
      preference. This sialidase has been shown to control transmembrane signalling for
      many cellular processes, including cell differentiation, cell growth and
      apoptosis, and human orthologue NEU3 is markedly up-regulated in various cancers.
      It is known to suppress apoptosis in cancer cells. Furthermore, its
      overexpression causes impaired glucose tolerance and hyper-insulinaemia together
      with overproduction of insulin in enlarged islets in the transgenic mice. The
      present review primarily summarizes our recent results, focusing on Neu3 as a
      regulator of transmembrane signalling.

PMID- 18632804
TI  - A unique caleosin in oil bodies of lily pollen.
AB  - In view of the recent isolation of stable oil bodies as well as a unique oleosin
      from lily pollen, this study examined whether other minor proteins were present
      in this lipid-storage organelle. Immunological cross-recognition using antibodies
      against three minor oil-body proteins from sesame suggested that a putative
      caleosin was specifically detected in the oil-body fraction of pollen extract. A
      cDNA fragment encoding this putative pollen caleosin, obtained by PCR cloning,
      was confirmed by immunodetection and MALDI-MS analyses of the recombinant protein
      over-expressed in Escherichia coli and the native form. Caleosin in lily pollen
      oil bodies seemed to be a unique isoform distinct from that in lily seed oil
      bodies.

PMID- 18632805
TI  - Multimodality probes: amphibian cars for molecular imaging.

PMID- 18632806
TI  - Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease.
AB  - The positron emission tomography (PET) radioligand N-methyl-11C-2-(4
      methylaminophenyl)-6-hydroxybenzothiazole (also known as 11C-6-OH-BTA-1 or 11C
      PIB) binds to amyloid-beta (Abeta), which accumulates pathologically in
      Alzheimer's disease (AD). Although 11C-PIB accumulation is greater in patients
      with AD than in healthy controls at a group level, the optimal method for
      discriminating between these 2 groups has, to our knowledge, not been
      established. We assessed the use of data-determined standardized voxels of
      interest (VOIs) to improve the classification capability of 11C-PIB scans on
      patients with AD. METHODS: A total of 16 controls and 14 AD age-matched patients
      were recruited. All subjects underwent a 11C-PIB scan and structural MRI. Binding
      potential (a measure of amyloid burden) was calculated for each voxel using the
      Logan graphical method with cerebellar gray matter as the reference region. Voxel
      maps were then partial-volume corrected and spatially normalized by MRI onto a
      standardized template. The subjects were divided into 2 cohorts. The first cohort
      (control, 12; AD, 9) was used for statistical parametric mapping analysis and
      delineation of data-based VOIs. These VOIs were tested in the second cohort
      (control, 4; AD, 5) of subjects. RESULTS: Statistical parametric mapping analysis
      revealed significant differences between control and AD groups. The VOI map
      determined from the first cohort resulted in complete separation between the
      control and the AD subjects in the second cohort (P < 0.02). Binding potential
      values based on this VOI were in the same range as other reported individual and
      mean cortical VOI results. CONCLUSION: A standardized VOI template that is
      optimized for control or AD group discrimination provides excellent separation of
      control and AD subjects on the basis of 11C-PIB uptake. This VOI template can
      serve as a potential replacement for manual VOI delineation and can eventually be
      fully automated, facilitating potential use in a clinical setting. To facilitate
      independent analysis and validation with more and a broader variety of subjects,
      this VOI template and the software for processing will be made available through
      the Internet.

PMID- 18632807
TI  - Colorectal tumor cells treated with 5-FU, oxaliplatin, irinotecan, and cetuximab
      exhibit changes in 18F-FDG incorporation corresponding to hexokinase activity and
      glucose transport.
AB  - The purpose of this study was to determine therapy-induced changes in 18F-FDG
      incorporation at the colorectal tumor cell level in response to conventional and
      novel chemotherapy agents and examine how these changes relate to factors
      involved in 18F-FDG incorporation. METHODS: SW620 cells were treated with
      inhibitory concentration of 50% (IC50) doses (determined by MTT) of 5
      fluorouracil (5-FU), oxaliplatin, and irinotecan; HCT-8 cells were treated with
      IC50 doses of irinotecan, cetuximab, and irinotecan plus cetuximab. 18F-FDG
      incorporation, glucose transport, hexokinase (HK) activity, adenosine
      triphosphate (ATP) content, annexin V binding, and cell cycle distribution were
      determined after 24-, 48-, and 72-h treatments. Eight-hour treatments with and
      without subsequent incubation in drug-free medium were also examined. A
      clonogenic assay was used to determine the tumor-forming ability of treated
      cells. RESULTS: Apoptosis was evident in SW620 cells, especially after treatment
      with irinotecan and 5-FU. 18F-FDG incorporation was increased in SW620 cells
      after 24- or 48-h treatments with some agents and in HCT-8 cells after irinotecan
      treatment but was decreased in all 72-h treatments or cell-line combinations
      including cetuximab. Treatment of SW620 cells for 8 h followed by 64 h in drug
      free medium also resulted in decreased 18F-FDG incorporation. Decreased 18F-FDG
      incorporation broadly corresponded to glucose transport in HCT-8 cells and to HK
      activity in SW620 cells. Inhibition of glucose transport decreased 18F-FDG
      incorporation into HCT-8 but not into SW620 cells. ATP levels were decreased by
      oxaliplatin treatment and increased at 48 or 72 h after irinotecan treatment.
      CONCLUSION: 18F-FDG incorporation is modulated by therapy-induced changes in both
      glucose transport and HK activity depending on the tumor cell. Colorectal cells
      treated with IC50 doses of cetuximab also exhibit decreased 18F-FDG.

PMID- 18632808
TI  - Biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in
      patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) involves the accumulation of monocyte-derived
      macrophages in the affected synovial tissue. This process of cell migration could
      be portrayed scintigraphically to monitor noninvasively the effects of therapy on
      the progress of the disease. For this purpose, labeling of purified autologous
      monocytes with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) at very high
      specific radioactivity has recently been developed. The aim of this study was to
      assess the biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled
      monocytes in adult patients with RA. METHODS: In 8 patients with RA, monocytes
      were isolated from 100 mL of blood and labeled with 99mTc-HMPAO to a yield of 10
      Bq/cell. Multiple whole-body scans were performed up to 20 h after reinjection of
      an average of 200 MBq of 99mTc-HMPAO-labeled monocytes. Urine and blood samples
      were collected. The fraction of administered activity in 7 source organs was
      quantified from the attenuation-corrected geometric mean counts in conjugate
      views. Radiation-absorbed doses were estimated with OLINDA/EXM software. RESULTS:
      Autologous monocytes labeled with 99mTc-HMPAO at high intracellular yields showed
      in vivo kinetics comparable with labeled leukocytes, with initial trapping in the
      lungs followed by distribution into the liver, spleen, and bone marrow. The
      radiation-absorbed estimates for 99mTc-HMPAO-labeled monocytes were comparable
      with those for 99mTc-HMPAO-labeled mixed white blood cells, with an effective
      dose of 0.011 mSv/MBq. CONCLUSION: 99mTc-HMPAO-labeled monocytes have
      biodistribution and radiation dosimetry similar to those of 99mTc-HMPAO-labeled
      mixed white blood cells and might therefore be used for in vivo monitoring of
      immunomodulating therapy in patients with RA.

PMID- 18632810
TI  - Novel reference region model reveals increased microglial and reduced vascular
      binding of 11C-(R)-PK11195 in patients with Alzheimer's disease.
AB  - 11C-(R)-PK11195 is a PET radiotracer for the quantification of peripheral
      benzodiazepine binding sites (PBBSs). The PBBS is a consistent marker of
      activated microglia, and 11C-(R)-PK11195 has been used to image microglial
      activity in the diseased brain and in neoplasia. However, the PBBS is also
      expressed in the brain vasculature (endothelium and smooth muscles), and no
      evidence, to our knowledge, exists of a change in the vascular PBBS in pathologic
      brains or of such a change having an effect on the quantification of 11C-(R)
      PK11195 binding. To investigate this issue, we have used a modified reference
      tissue model (SRTMV) that accounts for tracer vascular activity both in reference
      and target tissues and applied it for the estimation of binding potential (BP) in
      a cohort of patients with Alzheimer's disease (AD). METHODS: A total of 10
      patients with AD and 10 age-matched healthy subjects who underwent a 11C-(R)
      PK11195 scan were considered in the analysis. The time-activity curves of 11
      regions of interest were extracted using the Hammersmith maximum probability
      atlas. BPs were first estimated using the standard simplified reference-tissue
      model (SRTM) with the reference tissue computed with a supervised selection
      algorithm. Subsequently, we applied an SRTMV that models PBBS vascular activity
      using an additional linear term for both target (VbT) and reference (VbR) regions
      accounting for vascular tracer activity (C(B)), whereas C(B) was extracted
      directly from the images. VbR was fixed to 5%, and R1, k2, BP, and VbT were
      estimated. PBBS density in the vasculature was also assessed by
      immunocytochemistry on a separate cohort of young and elderly controls and 3 AD
      postmortem brains. RESULTS: The inclusion of a vascular component in the SRTM
      increased BPs in all subjects, but the amount of the increase was different
      (about 11.9% in controls and 16.8% in patients with AD). In addition, average VbT
      values derived using the SRTMV were 4.22% for controls but only 2.87% in patients
      with AD. Immunochemistry showed reduced PBBS expression in AD due to vascular
      fibrosis. CONCLUSION: The reduction of VbT in AD can be interpreted as a
      consequence of 2 independent but concurring phenomena. The vascular fibrosis in
      the AD brain causes the well-documented decrease of the size of lumens and the
      reduction of blood volume. At the same time, the fibrotic process determines the
      loss of vascular PBBS, particularly in smooth muscles, as here documented by
      immunochemistry. The inclusion of the additional vascular component in the SRTM
      effectively models these 2 concurrent processes and amplifies the BP in AD more
      than in controls because of the decrease in tracer binding to the vasculature in
      the disease cohort.

PMID- 18632811
TI  - Quantitative analysis of norepinephrine transporter in the human brain using PET
      with (S,S)-18F-FMeNER-D2.
AB  - (S,S)-18F-FMeNER-D2 was recently developed as a radioligand for the measurement
      of norepinephrine transporter imaging with PET. In this study, a norepinephrine
      transporter was visualized in the human brain using this radioligand with PET and
      quantified by several methods. METHODS: PET scans were performed on 10 healthy
      men after intravenous injection of (S,S)-18F-FMeNER-D2. Binding potential
      relative to nondisplaceable binding (BP(ND)) was quantified by the indirect
      kinetic, simplified reference-tissue model (SRTM), multilinear reference-tissue
      model (MRTM), and ratio methods. The indirect kinetic method was used as the gold
      standard and was compared with the SRTM method with scan times of 240 and 180
      min, the MRTM method with a scan time of 240 min, and the ratio method with a
      time integration interval of 120-180 min. The caudate was used as reference brain
      region. RESULTS: Regional radioactivity was highest in the thalamus and lowest in
      the caudate during PET scanning. BP(ND) values by the indirect kinetic method
      were 0.54 +/- 0.19 and 0.35 +/- 0.25 in the thalamus and locus coeruleus,
      respectively. BP(ND) values found by the SRTM, MRTM, and ratio methods agreed
      with the values demonstrated by the indirect kinetic method (r = 0.81-0.92).
      CONCLUSION: The regional distribution of (S,S)-18F-FMeNER-D2 in our study agreed
      with that demonstrated by previous PET and postmortem studies of norepinephrine
      transporter in the human brain. The ratio method with a time integration interval
      of 120-180 min will be useful for clinical research of psychiatric disorders for
      estimation of norepinephrine transporter occupancy by antidepressants without
      requiring arterial blood sampling and dynamic PET.

PMID- 18632812
TI  - Deep-inspiration breath-hold PET/CT of lung cancer: maximum standardized uptake
      value analysis of 108 patients.
AB  - Our aim was to compare the maximum standardized uptake value (SUVmax) between
      breath-hold (BH) PET/CT and free-breathing (FB) PET/CT. METHODS: The features of
      phantom data were analyzed, after which a clinical study was performed. A total
      of 108 consecutive patients with lung cancer were examined using lutetium
      oxyorthosilicate (LSO)-based PET/CT. The patients were instructed to breathe
      freely during FB PET/CT. In BH PET/CT, the patients were instructed to hold their
      breath in the maximal inspiration position during the scout scan, for 10 s of the
      CT scan, and for as long as possible during the PET scan. BH time was recorded
      using a respiratory monitoring device. The %BH-index was defined as the
      percentage difference between SUVmax of FB PET and that of BH PET. Statistical
      analyses were performed using the following factors: %BH-index, age, body mass
      index, 18F-FDG dosage, blood glucose, BH time, lesion size, and location.
      RESULTS: The highest %BH-index was 223.2. %BH-index in the lower lung area was
      significantly higher than that in the upper lung area (51.8 +/- 49.5 vs. 16.9 +/-
      25.6, respectively). Lesion volume and maximum diameter in the high-%BH-index
      group were significantly lower than those in the low-%BH-index group, with the
      use of a %BH-index cutoff value of 37.l. CONCLUSION: SUVmax of FB PET should not
      be taken as accurate, especially in the lower lung area and for small pulmonary
      lesions. BH PET/CT is expected to enable precise measurement of SUVmax and is
      thus recommended as part of the standard protocol for lung cancer.

PMID- 18632814
TI  - Subcellular distribution and metabolism studies of the potential myocardial
      imaging agent [99mTc(N)(DBODC)(PNP5)]+.
AB  - 99mTc(N)-DBODC5 is the lead compound of a new series of monocationic 99mTc(N)
      based potential myocardial imaging agents that exhibit original biodistribution
      properties. This study was addressed to elucidate the mechanisms of distribution,
      retention, and elimination of this promising 99mTc(N)-agent. METHODS: The sex
      related in vitro and in vivo stability and the subcellular distribution of
      99mTc(N)-DBODC5 were investigated. Studies were performed by considering binding
      to the serum proteins; stability in rat serum, human serum, and rat liver
      homogenates; and the chemical integrity of the complex after extraction from rat
      tissues such as heart, liver, and kidney, as well as from intestinal fluids and
      urine. The effect of cyclosporin A on the in vivo pharmacokinetic properties of
      99mTc(N)-DBODC5 was also evaluated. Subcellular distribution of 99mTc(N)-DBODC5
      in ex vivo rat heart was determined by standard differential centrifugation
      techniques. RESULTS: No significant in vitro serum protein binding and no notable
      biotransformation of the native compound into different species by the in vitro
      action of the serum and liver enzymes was evidenced. In vivo experiments showed
      that sex affects the pharmacokinetic profile of the 99mTc(N)-complexes including
      metabolism and excretion. Chromatographic profiles of 99mTc(N)-radioactivity
      extracted from tissues and fluids of female rats were always coincident with the
      control. Conversely, a small percentage of metabolized species was detected by
      high-performance liquid chromatography in liver extracts of male rats.
      Furthermore, administration of cyclosporin A caused a significant reduction of
      lung, liver, and kidney washout along with a considerable variation in activity
      distribution in the intestinal tract in both male and female rats, thus
      indicating a possible implication of Pgp transporters in determining the biologic
      behavior of 99mTc(N)-DBODC5. However, this phenomenon was more pronounced in
      females. Subcellular distribution studies showed that 86.3% +/- 7.4% of 99mTc(N)
      DBODC5 was localized into mitochondrial fraction as a result of the interaction
      with the negative membrane potential. CONCLUSION: Evidence showing that the new
      99mTc(N)-myocardial tracers behave as multidrug resistance-associated protein P
      glycoprotein substrates, combined with their selective mitochondrial
      accumulation, strongly supports the possibility that diagnostic application of
      99mTc(N)-DBODC5 can be extended to tumor imaging and noninvasive multidrug
      resistance studies.

PMID- 18632815
TI  - PET/MRI dual-modality tumor imaging using arginine-glycine-aspartic (RGD)
      conjugated radiolabeled iron oxide nanoparticles.
AB  - The purpose of this study was to develop a bifunctional iron oxide (IO)
      nanoparticle probe for PET and MRI scans of tumor integrin alphavbeta3
      expression. METHODS: Polyaspartic acid (PASP)-coated IO (PASP-IO) nanoparticles
      were synthesized using a coprecipitation method, and particle size and magnetic
      properties were measured. A phantom study was used to assess the efficacy of PASP
      IO as a T2-weighted MRI contrast agent. PASP-IO nanoparticles with surface amino
      groups were coupled to cyclic arginine-glycine-aspartic (RGD) peptides for
      integrin alphavbeta3 targeting and macrocyclic 1,4,7,10-tetraazacyclododecane
      N,N',N'',N''',-tetraacetic acid (DOTA) chelators for PET after labeling with
      64Cu. IO nanoparticle conjugates were further tested in vitro and in vivo to
      determine receptor targeting efficacy and feasibility for dual PET/MRI. RESULTS:
      PASP-IO nanoparticles made by single-step reaction have a core size of 5 nm with
      a hydrodynamic diameter of 45 +/- 10 nm. The saturation magnetization of PASP-IO
      nanoparticles is about 117 emu/g of iron, and the measured r2 and r2* are 105.5
      and 165.5 (s.mM)(-1), respectively. A displacement competitive binding assay
      indicates that DOTA-IO-RGD conjugates bound specifically to integrin alphavbeta3
      in vitro. Both small-animal PET and T2-weighted MRI show integrin-specific
      delivery of conjugated RGD-PASP-IO nanoparticles and prominent
      reticuloendothelial system uptake. CONCLUSION: We have successfully developed an
      IO-based nanoprobe for simultaneous dual PET and MRI of tumor integrin
      expression. The success of this bifunctional imaging approach may allow for
      earlier tumor detection with a high degree of accuracy and provide further
      insight into the molecular mechanisms of cancer.

PMID- 18632816
TI  - Whole-body biodistribution and radiation dosimetry of the new cardiac tracer
      99mTc-N-DBODC.
AB  - Our purpose was to evaluate the safety profile and biodistribution behavior in
      healthy human volunteers of the new myocardial perfusion tracer
      bis[(dimethoxypropylphosphanyl)ethyl]ethoxyethylamine N,N'
      bis(ethoxyethyl)dithiocarbamato nitrido technetium(V) (99mTc-N-DBODC). METHODS:
      Ten healthy male volunteers were injected with 99mTc-N-DBODC under both stress
      and rest conditions. Anterior and posterior planar gamma-camera images were
      collected at 5, 30, 60, 240, and 1,440 min after injection, with organ uptake
      quantified by region-of-interest analysis. Tracer kinetics in body fluids were
      determined by collecting blood and urine samples at different time points.
      RESULTS: After injection, 99mTc-N-DBODC showed significant accumulation in the
      myocardium and prolonged retention. Under rest conditions, uptake in the heart,
      lungs, and liver at 5 min after injection was 1.67% +/- 0.13%, 1.16% +/- 0.07%,
      and 10.85% +/- 1.72%, respectively, of administered activity. Under stress
      conditions, heart uptake was significantly higher (2.07% +/- 0.22%).
      Radioactivity in the liver decreased to 3.64% +/- 0.98% and 2.37% +/- 0.48% at 60
      and 240 min, respectively, after injection. This rapid liver clearance led to
      favorable heart-to-liver ratios, reaching values of 0.74 +/- 0.13 at rest and
      1.26 +/- 0.28 during exercise 60 min after tracer administration. Radiation dose
      estimates were comparable to those obtained with other myocardial perfusion
      cationic compounds. CONCLUSION: The high uptake in the myocardium and the fast
      liver washout of 99mTc-N-DBODC will allow SPECT images of the left ventricle to
      be acquired early and with excellent quality.

PMID- 18632817
TI  - Assessment of the influence of atrial fibrillation on gated SPECT perfusion data
      by comparison with simultaneously acquired nongated SPECT data.
AB  - The impact of arrhythmias on the evaluation of perfusion data from myocardial
      gated SPECT has been assessed by comparing arrhythmic patients with nonarrhythmic
      patients or by simulating rhythm disturbances. Whether gating-related artifacts
      may have a clinically relevant influence on the evaluation of perfusion in atrial
      fibrillation (AF) patients is still uncertain. Recently, collection of nongated
      and gated datasets during the same SPECT acquisition has become possible. The aim
      of this study was to examine the difference in myocardial perfusion between
      simultaneously acquired gated and nongated SPECT data in AF patients. METHODS: In
      44 consecutive AF patients who underwent myocardial perfusion SPECT for standard
      clinical indications, both a gated and a nongated study were simultaneously
      acquired. Perfusion was estimated in a masked manner on a 20-segment model using
      an established scoring scheme. RESULTS: Agreement was good between the gated and
      nongated perfusion scores on a segment basis; the agreement for resting scores
      was the highest, with those for stress and difference scores being lower
      (Spearman rho = 0.82, 0.74, and 0.55, respectively). On a patient basis, a
      similar trend was seen in summed resting scores (rho = 0.911), summed stress
      scores (rho = 0.779), and summed difference scores (rho = 0.596). When summed
      stress and summed difference data were grouped by severity class (normal, mild
      abnormality, moderate abnormality, and severe abnormality), agreement decreased
      from rho = 0.818, kappa = 0.639, for summed stress score to rho = 0.549, kappa =
      0.367, for summed difference score. The severity class of inducible ischemia
      changed in 17 patients (39%) if a (summed) gated image was used instead of a
      standard nongated perfusion image. CONCLUSION: AF may have a clinically relevant
      impact on summed gated perfusion images, compared with images simultaneously
      obtained without gating in the same patients. Therefore, acquisition of a
      nongated SPECT study is mandatory for accurate assessment of myocardial perfusion
      in AF patients.

PMID- 18632818
TI  - Impact of angiogenesis-related gene expression on the tracer kinetics of 18F-FDG
      in colorectal tumors.
AB  - 18F-FDG kinetics are primarily dependent on the expression of genes associated
      with glucose transporters and hexokinases but may be modulated by other genes.
      The dependency of 18F-FDG kinetics on angiogenesis-related gene expression was
      evaluated in this study. METHODS: Patients with primary colorectal tumors (n =
      25) were examined with PET and 18F-FDG within 2 days before surgery. Tissue
      specimens were obtained from the tumor and the normal colon during surgery, and
      gene expression was assessed using gene arrays. RESULTS: Overall, 23 angiogenesis
      related genes were identified with a tumor-to-normal ratio exceeding 1.50.
      Analysis revealed a significant correlation between k1 and vascular endothelial
      growth factor (VEGF-A, r = 0.51) and between fractal dimension and angiopoietin-2
      (r = 0.48). k3 was negatively correlated with VEGF-B (r = -0.46), and a positive
      correlation was noted for angiopoietin-like 4 gene (r = 0.42). A multiple linear
      regression analysis was used for the PET parameters to predict the gene
      expression, and a correlation coefficient of r = 0.75 was obtained for VEGF-A and
      of r = 0.76 for the angiopoietin-2 expression. Thus, on the basis of these
      multiple correlation coefficients, angiogenesis-related gene expression
      contributes to about 50% of the variance of the 18F-FDG kinetic data. The global
      18F-FDG uptake, as measured by the standardized uptake value and influx, was not
      significantly correlated with angiogenesis-associated genes. CONCLUSION: 18F-FDG
      kinetics are modulated by angiogenesis-related genes. The transport rate for 18F
      FDG (k1) is higher in tumors with a higher expression of VEGF-A and angiopoietin
      2. The regression functions for the PET parameters provide the possibility to
      predict the gene expression of VEGF-A and angiopoietin-2.

PMID- 18632821
TI  - Long-term survival of patients with viable and nonviable aneurysms assessed by
      99mTc-MIBI SPECT and 18F-FDG PET: a comparative study of medical and surgical
      treatment.
AB  - The prognostic value of myocardial viability assessment on left ventricular (LV)
      aneurysms remains undetermined. We aimed, first, to evaluate the long-term
      survival benefit of assessing the viability of the aneurysmal myocardium in
      patients with ischemic cardiomyopathy and, second, in the revascularization
      subgroup, to compare the short-term effects on LV function and clinical symptoms
      in patients treated by revascularization alone or by revascularization plus
      aneurysmectomy. METHODS: Seventy consecutive patients with an LV aneurysm who
      underwent 99mTc-sestamibi SPECT and 18F-FDG PET were followed up for a median of
      6.8 y (range, 0.1-8.8 y). Only cardiac death during follow-up served as the
      endpoint. Patients were classified into 4 groups by aneurysmal viability and by
      treatment strategy (medical or surgical). Further, the effects of aneurysmectomy
      on LV function at 3 mo were evaluated by an analysis of revascularized patients
      grouped by aneurysmal viability and by aneurysmectomy. RESULTS: Twenty-four
      patients were assigned to medical therapy, and 46 patients were assigned to
      surgery (18 revascularization alone and 28 revascularization plus
      aneurysmectomy). The annual cardiac mortality rate in patients with a viable
      aneurysm treated medically (n = 10) was significantly higher than that in
      patients with a viable aneurysm treated surgically (n = 23) (11.6% vs. 1.5%, chi2
      = 12.87, P < 0.0001) and was also significant higher than that in patients with a
      nonviable aneurysm treated medically (n = 14) (chi2 = 4.13, P < 0.05) or
      surgically (n = 23) (chi2 = 10.46, P = 0.001). Multivariate analysis showed that
      the aneurysmal mismatch score (P = 0.003) and surgical therapy (P = 0.001) were
      independent predictors of cardiac death. Improvement of LV function and symptoms
      after revascularization (P < 0.05) was observed in patients with
      revascularization plus aneurysmectomy and in patients with a viable aneurysm and
      revascularization only. CONCLUSION: Viability in LV aneurysm in patients with
      ischemic cardiomyopathy was a negative independent predictor of survival.
      Compared with medical therapy, coronary revascularization was associated with
      improved long-term survival, symptoms, and LV function in patients with a viable
      aneurysm. These findings warrant further prospective investigations.

PMID- 18632820
TI  - Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein
      elevation by atherogenic risk reduction.
AB  - Vascular 18F-FDG uptake marker represents inflammation in atherosclerotic
      lesions, but whether inflammation can be reversed by risk-modifying interventions
      has not, to our knowledge, been demonstrated. In this study, we evaluated the
      change of vascular 18F-FDG uptake in response to lifestyle intervention on serial
      PET/CT scans and further assessed how the findings relate to atherogenic risk
      reduction. METHODS: A total of 60 healthy adults underwent 18F-FDG PET/CT scans
      and atherogenic risk-factor assessment at baseline and again after 17.1 +/- 8.3
      mo of practicing lifestyle modification. The PET/CT images were evaluated for the
      presence of vascular 18F-FDG lesions, and vessel-to-blood-pool 18F-FDG ratios
      were measured. Indices from summed ratios of positive lesions were compared and
      correlated to atherogenic risk factors. RESULTS: At follow-up, significant
      reductions in diastolic blood pressure (P < 0.05), total cholesterol (P < 0.05),
      and low-density lipoprotein level (P < 0.05) and an increase in high-density
      lipoprotein (HDL) level (P < 0.0001) were demonstrated. On the initial PET/CT
      scan, 50 of 60 subjects showed 1 or more 18F-FDG-positive lesions (5.9 +/-
      5.0/subject), leading to a total of 352 vascular sites. On follow-up, 18F-FDG
      positive lesions were significantly reduced to 2.1 +/- 2.2 sites per subject (P <
      0.0001) and a total of 124 sites (64.8% reduction). Follow-up 18F-FDG-positive
      rates were significantly reduced for the aorta and iliac arteries. In addition,
      significant reductions in the whole-body 18F-FDG index from 1.39 +/- 1.23 to 0.53
      +/- 0.59 (P < 0.0001) and carotid 18F-FDG index from 0.08 +/- 0.16 to 0.03 +/-
      0.06 (P = 0.01) were shown. The whole-body 18F-FDG index correlated with total
      cholesterol (P < 0.05) and HDL level (P < 0.05), and the magnitude of reduction
      in the 18F-FDG index closely correlated to the amount of increase in plasma HDL
      level (P = 0.005). CONCLUSION: Our study demonstrated that vascular 18F-FDG
      uptake is reversed in response to atherogenic risk reduction by lifestyle
      intervention and that the magnitude of improvement correlates to increases in
      plasma HDL levels. Thus, serial 18F-FDG PET/CT may be useful for monitoring
      improvements in the inflammatory component of atherosclerotic lesions in response
      to risk modification.

PMID- 18632819
TI  - Time course of alterations in myocardial glucose utilization in the Zucker
      diabetic fatty rat with correlation to gene expression of glucose transporters: a
      small-animal PET investigation.
AB  - Diabetic cardiomyopathy is associated with abnormalities in glucose metabolism.
      We evaluated myocardial glucose metabolism in a rodent model of type 2 diabetes,
      namely the Zucker diabetic fatty (ZDF) rat, and validated PET measurements of
      glucose uptake against gene and protein expression of glucose transporters
      (GLUTs). METHODS: Six lean and ZDF rats underwent small-animal PET at the age of
      14 wk and at the age of 19 wk. The imaging protocol consisted of a 60-min dynamic
      acquisition with 18F-FDG (18.5-29.6 MBq). Dynamic images were reconstructed using
      filtered backprojection with a 2.5 zoom on the heart and 40 frames per imaging
      session. PET measurements of myocardial glucose uptake (MGUp) rate and
      utilization were determined with an input function derived by the hybrid image
      blood-sampling algorithm on recovery-corrected anterolateral myocardial regions
      of interest. After the PET session at week 19 (W19), hearts were extracted for
      gene and protein expression analysis of GLUT-1 and GLUT-4. The dependence of MGUp
      on gene expression of GLUT-1 and GLUT-4 was characterized by multiple-regression
      analysis. RESULTS: MGUp in ZDF rats at both week 14 (W14) and W19 (P < 0.006) was
      significantly lower than MGUp in lean littermate control rats. Moreover, lean
      rats at W19 displayed significantly higher MGUp than they did at W14 (P = 0.007).
      Consistent with a diminished MGUp result, gene expression of GLUT-4 was
      significantly (P = 0.004) lower in ZDF rats. Finally, MGUp significantly (P =
      0.0003) correlated with gene expression of GLUT-4. CONCLUSION: Using small-animal
      PET, we confirmed alterations in myocardial glucose utilization and validated PET
      measurement of MGUp against gene and protein expression of GLUTs in the diabetic
      heart of an animal model of type 2 diabetes.

PMID- 18632822
TI  - Relationship between induction of phosphorylated H2AX and survival in breast
      cancer cells exposed to 111In-DTPA-hEGF.
AB  - The Auger electron-emitting radiopharmaceutical 111In
      diethylenetriaminepentaacetic acid human epidermal growth factor (111In-DTPA
      hEGF) binds the epidermal growth factor receptor (EGFR), is internalized, and
      translocates to the nucleus. The purpose of this study was to investigate the
      relationship between EGFR expression, DNA damage, and cytotoxicity in cells
      exposed to 111In-DTPA-hEGF. METHODS: Breast cancer cell lines with a range of
      EGFR expression levels were exposed to 111In-DTPA-hEGF or gamma-radiation. The
      cell lines (followed by number of EGFR per cell in parentheses) were MDA-MB-468
      (1.3 x 10(6)), MDA-MB-231 (1.3 x 10(5)), and MCF-7 (1.5 x 10(4)). The proportion
      of radioactivity partitioning into the nucleus was measured by cell
      fractionation. DNA double-strand breaks were evaluated using the gamma-H2AX
      assay. Clonogenic survival assays were used to measure cytotoxicity. RESULTS: All
      data are presented as mean +/- SD. The amount of 111In-DTPA-hEGF that
      translocated to the nucleus (in mBq/nucleus) in MDA-MB-468, MDA-MB-231, and MCF-7
      cells incubated with 111In-DTPA-hEGF (5.2 MBq/mL, 43 nM) for 20 h was 131 +/- 6,
      8.1 +/- 0.1, and 1.1 +/- 0.9, respectively. The number of gamma-H2AX foci per
      nucleus was 35 +/- 15, 19 +/- 10, and 1.7 +/- 0.3, respectively. A reduction in
      the surviving fraction (SF) in MDA-MB-468 (0.013 +/- 0.001) and MDA-MB-231 (0.5
      +/- 0.1) but not in MCF-7 cells after exposure to 111In-DTPA-hEGF (5.2 MBq/mL, 43
      nM) for 20 h has been demonstrated. The SF of MDA-MB-468 cells after exposure to
      DTPA-EGF (43 nM) and 111In-acetate (5.2 MBq/mL) for 20 h was 0.5 +/- 0.1 and 0.53
      +/- 0.05, respectively. MDA-MB-468 was the most sensitive of the cell lines to
      gamma-irradiation, with an SF after 2 Gy of 0.45 +/- 0.04, compared with 0.7 +/-
      0.1 and 0.8 +/- 0.1 for MCF-7 and MDA-MB-231, respectively. The number of gamma
      H2AX foci per nucleus in MDA-MB-468 cells correlated with the concentration,
      specific activity, and incubation time of 111In-DTPA-hEGF. CONCLUSION: DNA damage
      caused by 111In-DTPA-hEGF correlates with the EGFR expression level of the
      exposed cells and with concentration, specific activity, and incubation time of
      111In-DTPA-hEGF. The gamma-H2AX assay may be a useful biomarker to predict and
      monitor the outcome of treatment with 111In-DTPA-hEGF.

PMID- 18632824
TI  - Opioid receptor PET reveals the psychobiologic correlates of reward processing.
AB  - Little is known about the neurobiologic correlates of human personality. On the
      basis of the key role of the central opioidergic system in addiction and
      substance abuse, we investigated the relationship between certain personality
      traits that are supposed to be relevant in addiction and the opioid receptor
      status in healthy subjects. METHODS: We investigated 23 healthy male volunteers
      who were extensively clinically tested to exclude substance abuse. All of the
      subjects underwent 1 PET scan with the subtype-nonselective opioidergic
      radioligand 18F-fluoroethyl-diprenorphine under resting conditions without
      sensory or cognitive stimulation. Subsequently, the subjects were psychologically
      tested for the personality traits novelty seeking, harm avoidance, reward
      dependence, and persistence, according to Cloninger's biosocial model of
      personality. The binding potential (BP) as a parameter of regional cerebral
      opioid receptor availability was computed by means of the modified Logan plot
      using the occipital cortex as a reference region. Further imaging data analysis
      was performed using statistical parametric mapping; after stereotactic
      normalization, the correlations were calculated between the regional BP and the
      psychologic scores on a voxel-by-voxel basis. RESULTS: The correlation analysis
      between personality dimensions and opioid receptor availability showed a
      significant (P < 0.001) positive correlation between the scores of reward
      dependence and the BP of the bilateral ventral striatum with nucleus accumbens (z
      scores, 4.52 and 4.33, respectively). The additionally performed region-of
      interest-based correlation analysis yielded correlation coefficients of r = 0.84
      and r = 0.81 for the left and right ventral striata, respectively. No further
      significant correlations were detectable between the other personality dimensions
      and cerebral opioid receptor binding. CONCLUSION: In healthy subjects,
      personality traits, which might be predisposing for addictive behavior, are
      correlated to the opioidergic neurotransmission in core structures of the human
      reward system.

PMID- 18632825
TI  - SPECT/CT.
AB  - In view of the commercial success of integrated PET/CT scanners, there is an
      increasing interest in comparable SPECT/CT systems. SPECT in combination with CT
      enables a direct correlation of anatomic information and functional information,
      resulting in better localization and definition of scintigraphic findings.
      Besides anatomic referencing, the added value of CT coregistration is based on
      the attenuation correction capabilities of CT. The number of clinical studies is
      limited, but pilot studies have indicated a higher specificity and a significant
      reduction in indeterminate findings. The superiority of SPECT/CT over planar
      imaging or SPECT has been demonstrated in bone scintigraphy, somatostatin
      receptor scintigraphy, parathyroid scintigraphy, and adrenal gland scintigraphy.
      Also, rates of detection of sentinel nodes by biopsy can be increased with
      SPECT/CT. This review highlights recent technical developments in integrated
      SPECT/CT systems and summarizes the current literature on potential clinical uses
      and future directions for SPECT/CT in cardiac, neurologic, and oncologic
      applications.

PMID- 18632826
TI  - 99mTc-labeled duramycin as a novel phosphatidylethanolamine-binding molecular
      probe.
AB  - With only 19 amino acids, duramycin is the smallest known polypeptide that has a
      defined 3-dimensional binding structure. Duramycin binds phosphatidylethanolamine
      (PtdE) at a 1:1 ratio with high affinity and exclusive specificity. As an
      abundant binding target, PtdE is a major phospholipid and accounts for about 20%
      of the phospholipid content in mammalian cellular membranes. PtdE is externalized
      to the surface of apoptotic cells and also becomes accessible in necrotic cells
      because of compromised plasma membrane integrity. Given the unique
      physicochemical properties of duramycin and the availability of PtdE in acute
      cell death, the goal of this study was to develop and evaluate 99mTc-duramycin as
      a novel molecular probe for imaging PtdE. METHODS: Duramycin is covalently
      modified with succinimidyl 6-hydrazinonicotinate acetone hydrazone (HYNIC) and
      labeled with 99mTc using a coordination chemistry involving tricine-phosphine
      coligands. The retention of PtdE-binding activities was confirmed using
      competition assays with PtdE-containing liposomes. The blood clearance,
      pharmacokinetics, and biodistribution of 99mTc-duramycin were measured in rats.
      Finally, 99mTc-duramycin binding to acute cell death in vivo was demonstrated
      using a rat model of acute myocardial infarction induced by ischemia and
      reperfusion and confirmed using autoradiography and histology. RESULTS: HYNIC
      derivatized duramycin with 1:1 stoicheometry was synthesized and confirmed by
      mass spectrometry. The radiolabeling efficiency was 80%-85%, radiochemical purity
      was 78%-89%, and specific activity was 54 GBq. The radiotracer was purified with
      high-performance liquid chromatography radiodetection before use. The specific
      uptake of 99mTc-duramycin in apoptotic cells, compared with that in viable
      control cells, was enhanced by more than 30-fold. This binding was competitively
      diminished in the presence of PtdE-containing liposomes but not by liposomes
      consisting of other phospholipid species. Intravenously injected 99mTc-duramycin
      has favorable pharmacokinetic and biodistribution profiles: it quickly clears
      from the circulation via the renal system, with a blood half-life of less than 4
      min in rats. The hepatic and gastrointestinal uptake were very low. 99mTc
      duramycin is completely unmetabolized in vivo, and the intact agent is recovered
      from the urine. Combined with a fast clearance and low hepatic background, the
      avid binding of 99mTc-duramycin to the infarcted myocardium quickly becomes
      conspicuous shortly after injection. The uptake of radioactivity in infarcted
      tissues was confirmed by autoradiography and histology. CONCLUSION: 99mTc
      duramycin is a stable, low-molecular-weight PtdE-binding radiopharmaceutical,
      with favorable in vivo imaging profiles. It is a strong candidate as a molecular
      probe for PtdE imaging and warrants further development and characterization.

PMID- 18632827
TI  - Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F
      FDG PET.
AB  - The purpose of this study was to retrospectively investigate the feasibility of
      11C-choline PET, compared with 18F-FDG PET, for the detection of hepatocellular
      carcinoma (HCC). METHODS: A total of 16 HCC lesions in 12 patients were examined
      with both 11C-choline PET and 18F-FDG PET. Tumor lesions were identified as areas
      of focally increased uptake, exceeding that of surrounding noncancerous liver
      tissue. For semiquantitative analysis, the tumor-to-liver (T/L) ratio was
      calculated by dividing the maximal standardized uptake value (SUV) in HCC lesions
      by the mean SUV in noncancerous liver tissue. RESULTS: 11C-choline PET showed a
      slightly higher detection rate than did 18F-FDG PET for detection of HCC (63% vs.
      50%, respectively), although this difference was not statistically significant.
      11C-choline PET had a better detection rate for moderately differentiated HCC
      lesions but not for those poorly differentiated (75% vs. 25%, respectively). In
      contrast, 18F-FDG PET exhibited the opposite behavior, with corresponding
      detection rates of 42% and 75%, respectively. The mean 11C-choline SUV and T/L
      ratio in moderately differentiated HCC lesions were higher than those in poorly
      differentiated HCC lesions. In contrast, the mean 18F-FDG SUV and T/L ratio in
      poorly differentiated HCC were higher than those in moderately differentiated
      HCC. These differences, however, were also not statistically significant.
      CONCLUSION: 11C-choline PET had a better detection rate for moderately
      differentiated HCC lesions but not for poorly differentiated HCC lesions, whereas
      18F-FDG PET produced the opposite result. 11C-choline is a potential tracer to
      complement 18F-FDG in detection of HCC lesions.

PMID- 18632828
TI  - Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier
      studied with (R)-11C-verapamil and PET.
AB  - The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high
      concentrations at the blood-brain barrier (BBB) and is believed to be implicated
      in resistance to central nervous system drugs. We used small-animal PET and (R)
      11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study
      the functional activity of P-gp at the BBB of rats. To enable a comparison with
      human PET data, we performed kinetic modeling to estimate the rate constants of
      radiotracer transport across the rat BBB. METHODS: A group of 7 Wistar Unilever
      rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1
      baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n =
      5) or vehicle (n = 2). RESULTS: After tariquidar administration, the distribution
      volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81
      vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially
      the same when only vehicle was administered. The increase in DV could be
      attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil
      into the brain, which was about 8-fold higher after tariquidar. A dose-response
      assessment with tariquidar provided an estimated half-maximum effect dose of 8.4
      +/- 9.5 mg/kg. CONCLUSION: Our data demonstrate that (R)-11C-verapamil PET
      combined with tariquidar administration is a promising approach to measure P-gp
      function at the BBB.

PMID- 18632829
TI  - 111In-octreotide is superior to 123I-metaiodobenzylguanidine for scintigraphic
      detection of head and neck paragangliomas.
AB  - In this study, we evaluated the diagnostic yield of somatostatin receptor
      scintigraphy (SRS), I-metaiodobenzylguanidine (MIBG) scintigraphy, and
      morphologic imaging (CT or MRI) in patients with head and neck paragangliomas.
      METHODS: In a university hospital setting, patients considered to have head and
      neck paraganglioma were referred to the outpatient endocrinology department and
      underwent CT or MRI, SRS, and MIBG imaging. For validation, we used a composite
      reference standard consisting of clinical and histologic data and CT or MRI, with
      which SRS and MIBG imaging were compared. Urinary metanephrine and
      normetanephrine measurements were also obtained. RESULTS: Twenty-nine
      consecutively referred patients (17 women and 12 men) were included and were
      found to have paraganglioma. Both morphologic and SRS were positive in 27
      patients (sensitivity, 93%, and 95% confidence interval [CI], 77%-98%, compared
      with the composite reference standard), whereas MIBG was positive in only 13
      patients (44%; 95% CI, 23%-61%) (P < 0.001, compared with SRS). On a lesion-based
      analysis, morphologic imaging detected 31 lesions (sensitivity, 82%; 95% CI, 65%
      92%), SRS detected 34 (89%; 95% CI, 75%-97%), and MIBG detected 15 (42%; 95% CI,
      26%-59%). SRS was superior to MIBG (P = 0.001). With SRS, a previously unknown
      carcinoid tumor was detected in 1 patient, and a carcinoid was suspected in
      another patient. MIBG detected an additional adrenal pheochromocytoma in 1
      patient. Urinary metanephrine or normetanephrine excretion was elevated in 6
      patients. The number of lesions on SRS and MIBG per patient correlated with the
      levels of abnormal metanephrine or normetanephrine excretion (P = 0.005 and P =
      0.02, respectively). CONCLUSION: SRS was superior to MIBG in patients with highly
      suspected head and neck paraganglioma.

PMID- 18632830
TI  - Gene expression patterns and tumor uptake of 18F-FDG, 18F-FLT, and 18F-FEC in
      PET/MRI of an orthotopic mouse xenotransplantation model of pancreatic cancer.
AB  - Our aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy
      3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-FEC) in human
      pancreatic tumor cell lines after xenotransplantation into SCID mice and to
      correlate tumor uptake with gene expression of membrane transporters and rate
      limiting enzymes for tracer uptake and tracer retention. METHODS: Four weeks
      after orthotopic inoculation of human pancreatic carcinoma cells (PancTuI,
      Colo357, and BxPC3) into SCID mice, combined imaging was performed with a small
      animal PET scanner and a 3-T MRI scanner using a dedicated mouse coil. Tumor-to
      liver uptake ratios (TLRs) of the tracers were compared with gene expression
      profiles of the tumor cell lines and both normal pancreatic tissue and pancreatic
      tumor tissue based on gene microarray analysis and quantitative polymerase chain
      reaction. RESULTS: 18F-FLT showed the highest tumor uptake, with a mean TLR of
      2.3, allowing correct visualization of all 12 pancreatic tumors. 18F-FDG detected
      only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in
      visible tumors. 18F-FEC did not show any tumor uptake. Gene array analysis
      revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping
      and pancreas-specific glucose transporter 2 were significantly downregulated
      whereas thymidine kinase 1, responsible for 18F-FLT trapping, was significantly
      upregulated in the tumor cell lines, compared with normal pancreatic duct cells
      and pancreatic tumor tissue. Relevant genes involved in the uptake of 18F-FEC
      were predominantly unaffected or downregulated in the tumor cell lines.
      CONCLUSION: In comparison to 18F-FDG and 18F-FEC, 18F-FLT was the PET tracer with
      the highest and most consistent uptake in various human pancreatic tumor cell
      lines in SCID mice. The imaging results could be explained by gene expression
      patterns of membrane transporters and enzymes for tracer uptake and retention as
      measured by gene array analysis and quantitative polymerase chain reaction in the
      respective cell lines. Thus, standard molecular techniques provided the basis to
      help explain model-specific tracer uptake patterns in xenotransplanted human
      tumor cell lines in mice as observed by PET.

PMID- 18632831
TI  - Breast cancer staging in a single session: whole-body PET/CT mammography.
AB  - Our objective was to compare the diagnostic accuracy of an all-in-one protocol of
      whole-body 18F-FDG PET/CT and integrated 18F-FDG PET/CT mammography with the
      diagnostic accuracy of a multimodality algorithm for initial breast cancer
      staging. METHODS: Forty women (mean age, 58.3 y; range, 30.8-78.4 y; SD, 12 y)
      with suspected breast cancer were included. For the primary tumor, we compared
      18F-FDG PET/CT mammography versus MRI mammography; for axillary lymph node
      status, 18F-FDG PET/CT versus clinical investigation and ultrasound; and for
      distant metastases, 18F-FDG PET/CT versus a multimodality staging algorithm.
      Histopathology and clinical follow-up served as the standard of reference. The
      Fisher exact test evaluated the significance of differences (P < 0.05).
      Alterations in patient management caused by 18F-FDG PET/CT were documented.
      RESULTS: No significant differences were found in the detection rate of breast
      cancer lesions (18F-FDG PET/CT, 95%; MRI, 100%; P = 1). 18F-FDG PET/CT correctly
      classified lesion focality significantly more often than did MRI (18F-FDG PET/CT,
      79%; MRI, 73%; P < 0.001). MRI correctly defined the T stage significantly more
      often than did 18F-FDG PET/CT (MRI, 77%; 18F-FDG PET/CT, 54%; P = 0.001). 18F-FDG
      PET/CT detected axillary lymph node metastases in 80% of cases; clinical
      investigation/ultrasound, in 70%. This difference was not statistically
      significant (P = 0.067). Distant metastases were detected with 18F-FDG PET/CT in
      100% of cases, and the multimodality algorithm identified distant metastases in
      70%. This difference was not statistically significant (P = 1). Three patients
      had extraaxillary lymph node metastases that were detected only by PET/CT
      (cervical, retroperitoneal, mediastinal/internal mammary group). 18F-FDG PET/CT
      changed patient management in 12.5% of cases. CONCLUSION: Our data suggest that a
      whole-body 18F-FDG PET/CT mammography protocol may be used for staging breast
      cancer in a single session. This initial assessment of the 18F-FDG PET/CT
      protocol indicates similar accuracy to MRI for the detection of breast cancer
      lesions. Although MRI seems to be more accurate when assessing the T stage of the
      tumor, 18F-FDG PET/CT seems able to more accurately define lesion focality.
      Although 18F-FDG PET/CT mammography was able to detect axillary lymph node
      metastases with a high sensitivity, this method cannot soon be expected to
      replace the combination of clinical examination, ultrasound, and sentinel lymph
      node biopsy for axillary assessment.

PMID- 18632832
TI  - What is the role of the aorta in directing coronary blood flow?

PMID- 18632833
TI  - Aortic valve calcification: basic science to clinical practice.
AB  - Calcific aortic valve stenosis is the result of regulated cell processes. The
      histological hallmarks are inflammation and a remodelling of the extracellular
      matrix leading to bone formation. In the last 15 years the view has changed from
      it being an unmodifiable degenerative disease to an active biological process
      regulated by highly conserved ubiquitous cellular pathways. Many mechanisms and
      risk factors are the same as in atherosclerosis. Thus, statins and angiotensin II
      antagonists seemed promising treatment options. However, clinical trials failed
      to support this. This review describes the current understanding of major
      molecular mechanisms and discusses their role in clinical practice and possible
      therapy.

PMID- 18632834
TI  - The Chinese coronary artery bypass grafting registry study: analysis of the
      national multicentre database of 9248 patients.
AB  - The past decade in China has heralded a rapid increase in surgical coronary
      revascularisation, and coronary artery bypass grafting (CABG) has now been
      possible in an increasingly high-risk population in China. However, little is
      known about the current status of CABG surgery in contemporary China. The
      European System for Cardiac Operative Risk Evaluation (EuroSCORE) was introduced
      to China for risk adjustment in 2000 due to the absence of a local risk
      prediction model. Now, it is the most widely used risk prediction algorithm in
      China. Fuwai Hospital, Beijing, China has developed a national multicentre
      database of CABG patients, named the Chinese CABG Registry Study. We embarked on
      this study with a view to establishing risk stratification and outcome assessment
      following CABG in Chinese adults as well as to provide a potential clinical
      research tool for the future. The database will then serve to validate the widely
      used EuroSCORE model in Chinese patients and to develop a risk prediction model
      for Chinese patients undergoing CABG.

PMID- 18632835
TI  - Atrial fibrillation in heart failure: the chicken or the egg?
AB  - Atrial fibrillation (AF) and heart failure (HF) are the emerging epidemics of
      cardiovascular disease in the new millennium. Both are responsible for
      considerable morbidity and mortality and health budget expenditure. The advent of
      catheter ablation for patients with AF has provided important new insights into
      the relative contribution of AF to left ventricular dysfunction. The aim of this
      review is to discuss the complex interplay in the pathophysiology of AF and HF to
      improve our understanding of the basis for current treatment strategies and guide
      future research direction.

PMID- 18632836
TI  - Age-related changes of the dental aesthetic zone at rest and during spontaneous
      smiling and speech.
AB  - The aims of this study were to analyse lip line heights and age effects in an
      adult male population during spontaneous smiling, speech, and tooth display in
      the natural rest position and to determine whether lip line height follows a
      consistent pattern during these different functions. The sample consisted of 122
      randomly selected male participants from three age cohorts (20-25 years, 35-40
      years, and 50-55 years). Lip line heights were measured with a digital
      videographic method for smile analysis, which had previously been tested and
      found reliable. Statistical analysis of the data was carried out using
      correlation analysis, analysis of variance, and Tukey's post hoc tests. Maxillary
      lip line heights during spontaneous smiling were generally higher in the premolar
      area than at the anterior teeth. The aesthetic zone in 75 per cent of the
      participants included all maxillary teeth up to the first molar. Coherence in lip
      line heights during spontaneous smiling, speech, and tooth display in the natural
      rest position was confirmed by significant correlations. In older subjects,
      maxillary lip line heights decreased significantly in all situations. Lip line
      heights during spontaneous smiling were reduced by approximately 2 mm. In older
      participants, the mandibular lip line heights also changed significantly and
      teeth were displayed less during spontaneous smiling. Mandibular tooth display in
      the rest position increased significantly. Upper lip length increased
      significantly by almost 4 mm in older subjects, whereas upper lip elevation did
      not change significantly. The significant increasing lip coverage of the
      maxillary teeth indicates that the effects of age should be included in
      orthodontic treatment planning.

PMID- 18632837
TI  - Craniofacial reference plane variation and natural head position.
AB  - Commonly used craniofacial reference planes such as Frankfort Horizontal (FH) and
      sella-nasion have shortcomings, including their variable interindividual
      orientation when related to true horizontal (HOR). Therefore, the aim of this
      study was to evaluate the potential usefulness of a range of craniofacial
      reference planes to HOR, including those which have not been investigated
      previously: the Krogman-Walker (KW) line, the neutral horizontal axis, the
      foramen magnum line, and the posterior maxillary plane. A sample of 57 (38
      female, 19 males) consecutive, pre-treatment orthodontic subjects aged 12-18
      years were photographically recorded in a standing mirror-guided natural head
      position (NHP). Cephalograms taken at the same time were traced, orientated to a
      plumb line (true vertical) transferred from the photograph, and measured.
      Descriptive statistical analysis including means and standard deviations (SDs)
      were used to describe average orientation and variability. Thirty-nine of these
      subjects were photographically recorded 2 months later to test the
      reproducibility of NHP. The results showed that the variability of the 11
      selected craniofacial reference planes related to HOR was generally high. The
      planes illustrating the lowest variability to HOR were FH and the KW line with
      SDs of 4.6 and 4.7 degrees, respectively. These, however, showed approximately
      double the variation in NHP reproducibility (mean square error 2.1 degree). The
      KW line and palatal plane were also on average orientated closest to HOR.
      Therefore, the KW line and palatal plane are potential substitutes for the
      commonly used reference planes in the absence of a reliable NHP. However, NHP
      still represents a more valid craniofacial reference system than the investigated
      reference planes.

PMID- 18632838
TI  - A randomized controlled study of early headgear treatment on occlusal stability-
      a 13 year follow-up.
AB  - The purpose of this investigation was to assess the long-term occlusal stability
      in a group treated early with headgear (HG) compared with a control group. The
      total study group comprised 68 children (40 males and 28 females) aged 7.6 years
      (standard deviation 0.3), randomly divided into two groups of equal size. In the
      first group, HG treatment was initiated immediately, while in the control group
      only minor interceptive procedures were performed during the follow-up period.
      Fixed appliance treatment, if needed, including extraction of permanent teeth due
      to crowding, was undertaken after the completion of early treatment. The records
      were available from the start of the early treatment and at follow-up after 2, 4,
      8, and 13 years. The US-weighted Peer Assessment Rating (PAR) Index, graded
      according to the severity of malocclusion, was used to evaluate occlusal
      stability. Little's Irregularity Index (LII)and intercanine distance in the lower
      arch were measured at all time periods. The Aesthetic Component (AC) of the Index
      of Orthodontic Treatment Need (IOTN) scores was used for evaluation of dental
      aesthetics at the last follow-up. Parametric tests were applied for statistical
      analyses, except for the evaluation of aesthetics, where a non-parametric test
      was used. No significant differences were found when long-term stability between
      the HG and control groups was evaluated at the 13 year follow-up. Lower PAR
      scores were observed in patients treated without extraction of teeth. A greater
      irregularity in lower incisor alignment before treatment was found in subjects
      later treated with extractions. The findings of this study seem to suggest that
      treatment timing has only a minor influence on stability.

PMID- 18632839
TI  - Success rate of miniscrews relative to their position to adjacent roots.
AB  - The purpose of this study was to evaluate, histologically, root contact,
      proximity to a root, and proximity to marginal bone level as possible risk
      factors for the failure of mini-screws when inserted between neighbouring teeth.
      Twenty mini-screws were inserted into the mandible of five beagle dogs. Each dog
      received two bracket screw bone anchors in each lower quadrant, between the roots
      of the second and third, and third and fourth premolars. Every six weeks, apical
      radiographs were taken and vital stains were administered. Twenty-five weeks
      after insertion of the screws, the dogs were sacrificed and specimens prepared
      for histological evaluation. The distance between the screw and the roots and
      between the screw and the marginal ridge level (MRL) were measured on the
      histological slides. The presence or absence of root contact was evaluated
      histologically on serial sections. The number of screws was too small to allow
      for sound statistical analysis of the factors under investigation. During the
      evaluation period, 11 screws were lost. Six screws were in contact with a tooth
      root and five of these were lost. In five sites, the distance between the screw
      and the tooth was less than 1.0 mm, but only one of these screws was lost. The
      distance between the screw and the marginal bone level was less than 1.0 mm for
      nine screws and seven of these were lost. The results of this limited study
      suggest that root contact and marginal position might be major risk factors for
      screw failure.

PMID- 18632840
TI  - Temperature rise and shear bond strength of bondable buccal tubes bonded by
      various light sources.
AB  - The objective of the present investigation was to determine the intrapulpal
      temperature changes and to compare the shear bond strength (SBS) of bondable
      buccal tubes bonded by high-intensity light sources. Ninety caries-free human
      first molar teeth extracted for periodontal reasons were used. For the
      temperature measurement test, 30 teeth were randomly divided into three groups (n
      = 10) whereas 60 teeth were used in three groups (n = 20) for SBS testing. Three
      light sources, high-intensity halogen, blue light-emitting diode (LED), and xenon
      plasma arc (PAC), were used for polymerization of Transbond XT. Temperature
      variations (Delta T) were recorded by a K-type thermocouple wire connected to a
      data logger. For SBS testing, a universal testing machine was used at a crosshead
      speed of 1 mm/minute until buccal tube bonding failure occurred. Data were
      analyzed using the Kruskal-Wallis test. The high-intensity halogen light resulted
      in significantly (P < 0.01) higher intrapulpal temperature changes than the LED
      or PAC. The results of the shear bond test revealed significant (P < 0.05)
      differences only between the halogen and LED groups. The findings of the present
      investigation showed that high-intensity curing devices can safely be used in
      bonding buccal tubes to molar teeth without causing a deleterious effect on the
      dental pulp.

PMID- 18632841
TI  - Cellular and extracellular factors in early root resorption repair in the rat.
AB  - The aim of this study was to investigate the role of extracellular matrix
      components, such as collagen type I, fibronectin, and osteopontin (OPN) during
      cementum repair following experimentally induced tooth movement, and to
      characterize the cells taking part in the regenerative process. The upper right
      first molars were moved mesially in 21 three-month-old male Wistar rats using a
      coil spring with a force of 0.5 N. After 9 days, the appliance was removed and
      the animals were killed in groups of three immediately after withdrawal of the
      force and 5, 7, 10, 12, 14, and 17 days later. Three rats served as non
      experimental control animals. The maxillae were prepared and processed for
      histological analysis. Together with the disappearance of the multinucleated
      odontoclasts from the resorption lacunae, signs of repair were visible 5 days
      after the release of the orthodontic force. The first signs of cementum repair
      were seen on day 10. The newly produced cementum was of the acellular extrinsic
      fibre type (AEFC) and reattachment was achieved with the principal periodontal
      ligament (PDL) fibres orientated almost perpendicular to the root surface. The
      initial interface formed between the old and new cementum, as well as the new
      AEFC, was characterized by a strong immunoreaction with OPN and collagen I
      antibody, but only a weak immunoreaction with the fibronectin antibody. Only a
      small number of mononuclear cells, which were involved in the repair process,
      showed a positive immunoreaction with the osteoblastic lineage markers runt
      related transcription factor 2 and osteocalcin. These same cells stained sparsely
      with muscle segment homeobox homologue 2, but not with the E11 antibody. Thus,
      most of the cells associated with this reparative activity on the surface of the
      lacunae were differentiated PDL cells of the fibroblastic phenotype. Cells with a
      defined osteoblastic phenotype seemed to be of minor importance in this repair
      process.

PMID- 18632842
TI  - Is the Royal London Space Analysis reliable and does it influence orthodontic
      treatment decisions?
AB  - The purpose of this study was to investigate the reliability of the Royal London
      Space Analysis (RLSA) and to evaluate its influence on orthodontic treatment
      decisions. Thirty-one case records were collected to represent various levels of
      crowding and different types of malocclusions. Seventeen examiners assessed these
      records and completed a data sheet that recorded information on their treatment
      decision. One month later, the examiners attended a course on the RLSA and then
      used the analysis to rescore the 31 cases. The models were also scored by the
      expert who led the course and these were then considered the 'gold standard'
      scores. After a further month, the examiners reapplied the RLSA and formulated a
      treatment plan for each set of patient records. A paired Student's t-test and
      intraclass correlation coefficient (ICC) were used to assess the agreement in
      scoring RLSA, a paired sample t-test was used to compare the scores with the gold
      standard, and finally the reliability in treatment planning was determined using
      kappa (kappa) statistics. The scores for lower arch crowding showed the highest
      inter-examiner agreement with an ICC of 0.93 whereas the lowest level of
      agreement was for upper arch space requirement with an ICC of 0.77. Intra
      examiner agreement was generally high, particularly for the assessment of lower
      arch crowding (ICC = 0.93) and lower arch space requirement (ICC = 0.88). There
      was excellent validity for all the examiners against the gold standard scores
      with a paired samples correlation ranging between 0.96 for lower arch crowding
      and 0.79 for upper arch space requirement. The intra-examiner reliability in
      treatment decision was only moderate, with an average kappa value of 0.52
      (maximum 0.82, minimum 0.24). Intra- and inter-examiner agreement for scoring the
      RLSA was acceptable. Nevertheless, the additional information obtained from the
      application of the RLSA did not have a substantial impact on the treatment
      decisions.

PMID- 18632843
TI  - CTGF inhibits BMP-7 signaling in diabetic nephropathy.
AB  - In diabetic nephropathy, connective tissue growth factor (CTGF) is upregulated
      and bone morphogenetic protein 7 (BMP-7) is downregulated. CTGF is known to
      inhibit BMP-4, but similar cross-talk between BMP-7 and CTGF has not been
      studied. In this study, it was hypothesized that CTGF acts as an inhibitor of BMP
      7 signaling activity in diabetic nephropathy. Compared with diabetic wild-type
      CTGF(+/+) mice, diabetic CTGF(+/-) mice had approximately 50% lower CTGF mRNA and
      protein, less severe albuminuria, no thickening of the glomerular basement
      membrane, and preserved matrix metalloproteinase (MMP) activity. Although the
      amount of BMP-7 mRNA was similar in the kidneys of diabetic CTGF(+/+) and CTGF(+/
      ) mice, phosphorylation of the BMP signal transduction protein Smad1/5 and
      expression of the BMP target gene Id1 were lower in diabetic CTGF(+/+) mice.
      Moreover, renal Id1 mRNA expression correlated with albuminuria (R = -0.86) and
      MMP activity (R = 0.76). In normoglycemic mice, intraperitoneal injection of CTGF
      led to a decrease of pSmad1/5 in the renal cortex. In cultured renal glomerular
      and tubulointerstitial cells, CTGF diminished BMP-7 signaling activity, evidenced
      by lower levels of pSmad1/5, Id1 mRNA, and BMP-responsive element-luciferase
      activity. Co-immunoprecipitation, solid-phase binding assay, and surface plasmon
      resonance analysis showed that CTGF binds BMP-7 with high affinity (Kd
      approximately 14 nM). In conclusion, upregulation of CTGF inhibits BMP-7 signal
      transduction in the diabetic kidney and contributes to altered gene
      transcription, reduced MMP activity, glomerular basement membrane thickening, and
      albuminuria, all of which are hallmarks of diabetic nephropathy.

PMID- 18632844
TI  - Podocyte-specific overexpression of the antioxidant metallothionein reduces
      diabetic nephropathy.
AB  - Podocytes are critical components of the selective filtration barrier of the
      glomerulus and are susceptible to oxidative damage. For investigation of the role
      of oxidative stress and podocyte damage in diabetic nephropathy, transgenic mice
      that overexpress the antioxidant protein metallothionein (MT) specifically in
      podocytes (Nmt mice) were produced. MT expression was increased six- and 18-fold
      in glomeruli of two independent lines of Nmt mice, and podocyte-specific
      overexpression was confirmed. Glomerular morphology and urinary albumin excretion
      were normal in Nmt mice. OVE26 transgenic mice, a previously reported model of
      diabetic nephropathy, were crossed with Nmt mice to determine whether an
      antioxidant transgene targeted to podocytes could reduce diabetic nephropathy.
      Double-transgenic OVE26Nmt mice developed diabetes similar to OVE26 mice, but MT
      overexpression reduced podocyte damage, indicated by more podocytes, less
      glomerular cell death, and higher density of podocyte foot processes. In
      addition, expansion of glomerular and mesangial volume were significantly less in
      OVE26Nmt mice compared with OVE26 mice. Four-month-old OVE26Nmt mice had a 70 to
      90% reduction in 24-h albumin excretion, but this protection does not seem to be
      permanent. These results provide evidence for the role of oxidative damage to the
      podocyte in diabetic mice and show that protection of the podocyte can reduce or
      delay primary features of diabetic nephropathy.

PMID- 18632845
TI  - Appraising the value of genomic association studies.

PMID- 18632846
TI  - Mechanisms of renal apoptosis in health and disease.
AB  - Apoptotic cell death is usually a response to the cell microenvironment.
      Apoptosis requires the activation of lethal molecules and the inactivation of
      prosurvival ones. Both are potential therapeutic targets. Apoptosis contributes
      to parenchymal cell loss in the course of acute and chronic renal injury.
      Apoptotic pathways that are active in glomerular and tubular epithelium include
      death induced by survival factor deprivation, death receptor activation,
      mitochondrial injury, endoplasmic reticulum stress, lysosomal destabilization,
      and caspase cascade activation. These pathways are not mutually exclusive, and
      stimulus-specific differences in the recruitment of apoptotic pathways have been
      observed. In some cases, the activation of a certain death pathway is redundant,
      and its inhibition does not prevent eventual cell death. This review summarizes
      recent advances in the field and discusses the rational basis to choose from the
      available tools to target apoptosis therapeutically.

PMID- 18632847
TI  - Cinacalcet reduces the set point of the PTH-calcium curve.
AB  - The calcimimetic cinacalcet increases the sensitivity of the parathyroid calcium
      sensing receptor to calcium and therefore should produce a decrease in the set
      point of the parathyroid hormone (PTH)-calcium curve. For investigation of this
      hypothesis, nine long-term hemodialysis patients with secondary
      hyperparathyroidism were given cinacalcet for 2 mo, the dosage was titrated per a
      protocol based on intact PTH and plasma calcium concentrations. Dialysis against
      low- and high-calcium (0.75 and 1.75 mM) dialysate was used to generate curves
      describing the relationship between PTH and calcium. Compared with precinacalcet
      levels, cinacalcet significantly reduced mean serum calcium, intact PTH and whole
      PTH (wPTH; all P < 0.001). The set points for PTH-calcium curves were
      significantly reduced, and both maximum and minimum levels of PTH (intact and
      whole) were significantly decreased. The calcium-mediated inhibition of PTH
      secretion was more marked after cinacalcet treatment. In addition, cinacalcet
      shifted the inverse sigmoidal curve of wPTH/non-wPTH ratio versus calcium to the
      left (i.e., less calcium was required to reduce the wPTH/non-wPTH ratio). In
      conclusion, cinacalcet increases the sensitivity of the parathyroids to calcium,
      causing a marked reduction in the set point of the PTH-calcium curve, in
      hemodialysis patients with secondary hyperparathyroidism.

PMID- 18632848
TI  - SUMOylation target sites at the C terminus protect Axin from ubiquitination and
      confer protein stability.
AB  - Axin is a scaffold protein for the beta-catenin destruction complex, and a
      negative regulator of canonical Wnt signaling. Previous studies implicated the
      six C-terminal amino acids (C6 motif) in the ability of Axin to activate c-Jun N
      terminal kinase, and identified them as a SUMOylation target. Deletion of the C6
      motif of mouse Axin in vivo reduced the steady-state protein level, which caused
      embryonic lethality. Here, we report that this deletion (Axin-DeltaC6) causes a
      reduced half-life in mouse embryonic fibroblasts and an increased susceptibility
      to ubiquitination in HEK 293T cells. We confirmed the C6 motif as a SUMOylation
      target in vitro, and found that mutating the C-terminal SUMOylation target
      residues increased the susceptibility of Axin to polyubiquitination and reduced
      its steady-state level. Heterologous SUMOylation target sites could replace C6 in
      providing this protective effect. These findings suggest that SUMOylation of the
      C6 motif may prevent polyubiquitination, thus increasing the stability of Axin.
      Although C6 deletion also caused increased association of Axin with Dvl-1, this
      interaction was not altered by mutating the lysine residues in C6, nor could
      heterologous SUMOylation motifs replace the C6 motif in this assay. Therefore,
      some other specific property of the C6 motif seems to reduce the interaction of
      Axin with Dvl-1.

PMID- 18632849
TI  - Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases.
AB  - Degradation of the cartilage proteoglycan aggrecan is a key early event in the
      development of osteoarthritis. Adamalysin with thrombospondin motifs (ADAMTS) -4
      and ADAMTS-5 are considered to be the main enzymes responsible for aggrecan
      breakdown, making them attractive drugs targets. Here we show that calcium
      pentosan polysulfate (CaPPS), a chemically sulfated xylanopyranose from
      beechwood, is a multifaceted exosite inhibitor of the aggrecanases and protects
      cartilage against aggrecan degradation. CaPPS interacts with the noncatalytic
      spacer domain of ADAMTS-4 and the cysteine-rich domain of ADAMTS-5, blocking
      activity against their natural substrate aggrecan with inhibitory concentration
      50 values of 10-40 nM but only weakly inhibiting hydrolysis of a nonglycosylated
      recombinant protein substrate. In addition, CaPPS increased cartilage levels of
      tissue inhibitor of metalloproteinases-3 (TIMP-3), an endogenous inhibitor of
      ADAMTS-4 and -5. This was due to the ability of CaPPS to block endocytosis of
      TIMP-3 mediated by low-density lipoprotein receptor-related protein. CaPPS also
      increased the affinity of TIMP-3 for ADAMTS-4 and -5 by more than 100-fold,
      improving the efficacy of TIMP-3 as an aggrecanase inhibitor. Studies with TIMP-3
      null mouse cartilage indicated that CaPPS inhibition of aggrecan degradation is
      TIMP-3 dependent. These unique properties make CaPPS a prototypic disease
      modifying agent for osteoarthritis.

PMID- 18632850
TI  - Extensive and bidirectional transfer of major histocompatibility complex class II
      molecules between donor and recipient cells in vivo following solid organ
      transplantation.
AB  - Intercellular transfer of surface molecules has been demonstrated in vitro, or in
      vivo under artificial situations. Transplantation is a unique clinical situation
      in which foreign major histocompatibility complex (MHC) molecules are
      deliberately introduced. This provides a model to study intercellular MHC
      transfer because donor MHC molecules can easily be tracked. Here we describe the
      bidirectional transfer of MHC class II molecules between donor and recipient
      cells after transplantation of vascularized kidney and cardiac allografts in
      mice. Cells that are positive for both donor and recipient MHC class II accounted
      for up to 30% of the donor MHC class II(+) population, suggesting that they play
      a significant role in the antigen presentation process. The majority of these
      cells were dendritic cells, but macrophages and B cells were also able to acquire
      foreign MHC molecules. Most double-positive cells were also positive for
      costimulatory molecules, indicating a capability to elicit a T-cell response.
      This transfer of MHC molecules between donor and recipient cells provides a link
      between the direct and indirect pathways of alloantigen presentation and suggests
      that MHC transfer is also likely to occur under normal physiological conditions,
      which has implications in the fields of infection, vaccination, and tumor
      immunology.

PMID- 18632851
TI  - Renal lesions associated with IgM-secreting monoclonal proliferations: revisiting
      the disease spectrum.
AB  - BACKGROUND AND OBJECTIVES: Since the first description of pathology of the kidney
      in Waldenstrom disease in 1970, there have been few reports on kidney
      complications of IgM-secreting monoclonal proliferations. Here, we aimed to
      revisit the spectrum of renal lesions occurring in patients with a serum
      monoclonal IgM. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fourteen patients
      with a circulating monoclonal IgM and a kidney disease related to B cell
      proliferation were identified retrospectively. Demographic, clinical, and
      laboratory data were assessed for each patient at the time of kidney biopsy.
      RESULTS: Seven patients had a nephrotic syndrome. Patients without nephrotic
      syndrome all had impaired renal function. Mean serum creatinine was 238
      micromol/L. For five patients, the diagnosis of monoclonal IgM preceded the
      kidney disease by 28.8 mo (range 12 to 60). Seven patients had Waldenstrom
      disease, two had a small B cell non-Hodgkin lymphoma, one had an IgM-excreting
      multiple myeloma, one had a marginal zone B cell lymphoma, and three had an IgM
      related disorder. Renal lesions included (1) intracapillary monoclonal deposits
      disease with granular, electron-dense IgM thrombi occluding capillary lumens (5);
      (2) atypical membranoproliferative glomerulonephritis (3); (3) lambda light chain
      amyloidosis (2) associated with mu deposits in one patient; (4) acute tubular
      necrosis (1); and (5) CD20(+) lymphomatous infiltration (3). Remission of the
      nephrotic syndrome was attained in three of seven patients, and renal function
      improved after chemotherapy. CONCLUSIONS: Although renal complications of IgM
      proliferations are rare, a wide spectrum of kidney lesions is observed, without
      correlation with the type of hematologic disorder.

PMID- 18632852
TI  - Natriuretic peptides in chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: B-type natriuretic peptide (BNP) and amino-terminal
      pro-B-type natriuretic peptide (NT-proBNP) are biomarkers of cardiovascular
      disease that is common in patients with chronic kidney disease (CKD). Conflicting
      data on the influence of glomerular filtration rate (GFR) on BNP and NT-proBNP
      levels in CKD may stem from failure to account fully for the effects of
      coexistent cardiac disease, dysfunction, and volume overload. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Prospective head-to-head comparison of plasma BNP
      and NT-proBNP in ambulatory euvolemic CKD patients with normal LV ejection
      fraction and no manifest cardiac or vascular disease. GFR was estimated by the
      Modification of Diet in Renal Disease formula, BNP and NT-proBNP measured using
      Abbott AxSYM and Roche Elecsys assays, respectively, and cardiac morphology and
      function assessed by transthoracic echocardiography. RESULTS: In 142 patients
      (42% female) of mean age 60 +/- 11 yr, mean left ventricular ejection fraction
      was 71% +/- 6%, GFR 38 +/- 14 ml/min per 1.73 m(2), and median BNP and NT-proBNP
      level 59 and 311 pg/ml, respectively. Multivariate predictors of NT-proBNP level
      were GFR, beta-blocker usage, LV mass index, and hemoglobin level. Plasma BNP was
      independently predicted by LV mass index and beta-blocker usage but not GFR. In
      the 74 patients without diastolic dysfunction, there was a significant rise in NT
      proBNP but not BNP as GFR declined. CONCLUSIONS: Unlike NT-proBNP, plasma BNP
      level is relatively independent of GFR. BNP may therefore be the more appropriate
      biomarker to screen for cardiac dysfunction in CKD.

PMID- 18632853
TI  - ERK1/2-mediated phosphorylation of small hepatitis delta antigen at serine 177
      enhances hepatitis delta virus antigenomic RNA replication.
AB  - The small hepatitis delta virus (HDV) antigen (SHDAg) plays an essential role in
      HDV RNA double-rolling-circle replication. Several posttranslational
      modifications (PTMs) of HDAgs, including phosphorylation, acetylation, and
      methylation, have been characterized. Among the PTMs, the serine 177 residue of
      SHDAg is a phosphorylation site, and its mutation preferentially abolishes HDV
      RNA replication from antigenomic RNA to genomic RNA. Using coimmunoprecipitation
      analysis, the cellular kinases extracellular signal-related kinases 1 and 2
      (ERK1/2) are found to be associated with the Flag-tagged SHDAg mutant (Ser-177
      replaced with Cys-177). In an in vitro kinase assay, serine 177 of SHDAg was
      phosphorylated directly by either Flag-ERK1 or Flag-ERK2. Activation of
      endogenous ERK1/2 by a constitutively active MEK1 (hemagglutinin-AcMEK1)
      increased phosphorylation of SHDAg at Ser-177; this phosphorylation was confirmed
      by immunoblotting using an antibody against phosphorylated S177 and mass
      spectrometric analysis. Interestingly, we found an increase in the HDV
      replication from antigenomic RNA to genomic RNA but not in that from genomic RNA
      to antigenomic RNA. The Ser-177 residue was critical for SHDAg interaction with
      RNA polymerase II (RNAPII), the enzyme proposed to regulate antigenomic RNA
      replication. These results demonstrate the role of ERK1/2-mediated Ser-177
      phosphorylation in modulating HDV antigenomic RNA replication, possibly through
      RNAPII regulation. The results may shed light on the mechanisms of HDV RNA
      replication.

PMID- 18632854
TI  - Human immunodeficiency virus type 1 envelope gp120 induces a stop signal and
      virological synapse formation in noninfected CD4+ T cells.
AB  - Human immunodeficiency virus type 1 (HIV-1)-infected T cells form a virological
      synapse with noninfected CD4(+) T cells in order to efficiently transfer HIV-1
      virions from cell to cell. The virological synapse is a specialized cellular
      junction that is similar in some respects to the immunological synapse involved
      in T-cell activation and effector functions mediated by the T-cell antigen
      receptor. The immunological synapse stops T-cell migration to allow a sustained
      interaction between T-cells and antigen-presenting cells. Here, we have asked
      whether HIV-1 envelope gp120 presented on a surface to mimic an HIV-1-infected
      cell also delivers a stop signal and if this is sufficient to induce a
      virological synapse. We demonstrate that HIV-1 gp120-presenting surfaces arrested
      the migration of primary activated CD4 T cells that occurs spontaneously in the
      presence of ICAM-1 and induced the formation of a virological synapse, which was
      characterized by segregated supramolecular structures with a central cluster of
      envelope surrounded by a ring of ICAM-1. The virological synapse was formed
      transiently, with the initiation of migration within 30 min. Thus, HIV-1 gp120
      presenting surfaces induce a transient stop signal and supramolecular segregation
      in noninfected CD4(+) T cells.

PMID- 18632855
TI  - Cleavage of poly(A)-binding protein by poliovirus 3C proteinase inhibits viral
      internal ribosome entry site-mediated translation.
AB  - The two enteroviral proteinases, 2A proteinase (2A(pro)) and 3C proteinase
      (3C(pro)), induce host cell translation shutoff in enterovirus-infected cells by
      cleaving canonical translation initiation factors. Cleavage of poly(A)-binding
      protein (PABP) by 3C(pro) has been shown to be a necessary component for host
      translation shutoff. Here we show that 3C(pro) inhibits cap-independent
      translation mediated by the poliovirus internal ribosome entry site (IRES) in a
      dose-dependent manner in HeLa translation extracts displaying cap-poly(A)
      synergy. This effect is independent of the stimulatory effect of 2A(pro) on IRES
      translation, and 3C(pro)-induced translation inhibition can be partially rescued
      by addition of recombinant PABP in vitro. 3C(pro) inhibits IRES translation on
      transcripts containing or lacking poly(A) tails, suggesting that cleavage of PABP
      and IRES trans-activating factors polypyrimidine tract-binding protein and poly
      r(C)-binding protein 2 may also be important for inhibition. Expression of
      3C(pro) cleavage-resistant PABP in cells increased translation of nonreplicating
      viral minigenome reporter RNAs during infection and also delayed and reduced
      virus protein synthesis from replicating RNA. Further, expression of cleavage
      resistant PABP in cells reduced the accumulation of viral RNA and the output of
      infectious virus. These results suggest that cleavage of PABP contributes to
      viral translation shutoff that is required for the switch from translation to RNA
      replication.

PMID- 18632856
TI  - Tumor necrosis factor alpha protects against lethal West Nile virus infection by
      promoting trafficking of mononuclear leukocytes into the central nervous system.
AB  - West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a
      significant cause of viral encephalitis in humans, especially in
      immunocompromised individuals. Previous studies have shown essential protective
      roles for antiviral cytokines (e.g., alpha interferon [IFN-alpha] and IFN-gamma)
      against WNV in mice. However, studies using cell culture offer conflicting
      answers regarding whether tumor necrosis factor alpha (TNF-alpha) has an anti-WNV
      function. To test the biological significance of TNF-alpha against WNV in vivo,
      experiments were performed with TNF receptor-1 (TNF-R1)-deficient and TNF-alpha
      depleted C57BL/6 mice. TNF-R1(-/-) mice had enhanced mortality and decreased
      survival time after WNV infection compared to congenic wild-type mice. Consistent
      with this, administration of a neutralizing anti-TNF-alpha monoclonal antibody
      also decreased survival after WNV infection. Relatively small differences in
      viral burdens in peripheral tissues of TNF-R1(-/-) mice were observed, and this
      occurrence correlated with a modest antiviral effect of TNF-alpha on primary
      macrophages but not dendritic cells. In contrast, the viral titers detected in
      the central nervous systems of TNF-R1(-/-) mice were significantly increased
      compared to those of wild-type mice, although TNF-alpha did not have a direct
      antiviral effect in primary neuron cultures. Whereas no defect in priming of
      adaptive B- and T-cell responses in TNF-R1(-/-) mice was observed, there were
      significant reductions in accumulations of CD8+ T cells and macrophages in the
      brain. Our data are most consistent with a model in which interaction of TNF
      alpha with TNF-R1 protects against WNV infection by regulating migration of
      protective inflammatory cells into the brain during acute infection.

PMID- 18632857
TI  - Differential cholesterol binding by class II fusion proteins determines membrane
      fusion properties.
AB  - The class II fusion proteins of the alphaviruses and flaviviruses mediate virus
      infection by driving the fusion of the virus membrane with that of the cell.
      These fusion proteins are triggered by low pH, and their structures are
      strikingly similar in both the prefusion dimer and the postfusion homotrimer
      conformations. Here we have compared cholesterol interactions during membrane
      fusion by these two groups of viruses. Using cholesterol-depleted insect cells,
      we showed that fusion and infection by the alphaviruses Semliki Forest virus
      (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar
      sterol dependence in laboratory and field isolates and in viruses passaged in
      tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by
      labeling with photocholesterol and by cholesterol extraction studies. In
      contrast, fusion and infection by numerous strains of the flavivirus dengue virus
      (DV) and by yellow fever virus 17D were cholesterol independent, and the DV
      fusion protein did not show significant cholesterol binding. SFV E1 is the first
      virus fusion protein demonstrated to directly bind cholesterol. Taken together,
      our results reveal important functional differences conferred by the cholesterol
      binding properties of class II fusion proteins.

PMID- 18632858
TI  - Induction of the Galpha(q) signaling cascade by the human immunodeficiency virus
      envelope is required for virus entry.
AB  - Binding of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein
      (Env) with the primary receptor CD4 and one of two coreceptors, CXCR4 or CCR5,
      activates a signaling cascade resulting in Rac-1 GTPase activation and
      stimulation of actin cytoskeletal reorganizations critical for HIV-1-mediated
      membrane fusion. The mechanism by which HIV-1 Env induces Rac-1 activation and
      subsequent actin cytoskeleton rearrangement is unknown. In this study, we show
      that Env-mediated Rac-1 activation is dependent on the activation of Galpha(q)
      and its downstream targets. Fusion and Rac-1 activation are mediated by Galpha(q)
      and phospholipase C (PLC), as shown by attenuation of fusion and Rac-1 activation
      in cells either expressing small interfering RNA (siRNA) targeting Galpha(q) or
      treated with the PLC inhibitor U73122. Rac-1 activation and fusion were also
      blocked by multiple protein kinase C inhibitors, by inhibitors of intracellular
      Ca2+ release, by Pyk2-targeted siRNA, and by the Ras inhibitor S-trans,trans
      farnesylthiosalicylic acid (FTS). Fusion was blocked without altering cell
      viability or cell surface localization of CD4 and CCR5. Similar results were
      obtained when cell fusion was induced by Env expressed on viral and cellular
      membranes and when cell lines or primary cells were the target. Treatment with
      inhibitors and siRNA specific for Galpha(i) or Galpha(s) signaling mediators had
      no effect on Env-mediated Rac-1 activation or cell fusion, indicating that the
      Galpha(q) pathway alone is responsible. These results could provide a new focus
      for therapeutic intervention with drugs targeting host signaling mediators rather
      than viral molecules, a strategy which is less likely to result in resistance.

PMID- 18632859
TI  - The transmembrane domain of the severe acute respiratory syndrome coronavirus
      ORF7b protein is necessary and sufficient for its retention in the Golgi complex.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) ORF7b (also called
      7b) protein is an integral membrane protein that is translated from a bicistronic
      open reading frame encoded within subgenomic RNA 7. When expressed independently
      or during virus infection, ORF7b accumulates in the Golgi compartment,
      colocalizing with both cis- and trans-Golgi markers. To identify the domains of
      this protein that are responsible for Golgi localization, we have generated a set
      of mutant proteins and analyzed their subcellular localizations by indirect
      immunofluorescence confocal microscopy. The N- and C-terminal sequences are
      dispensable, but the ORF7b transmembrane domain (TMD) is essential for Golgi
      compartment localization. When the TMD of human CD4 was replaced with the ORF7b
      TMD, the resulting chimeric protein localized to the Golgi complex. Scanning
      alanine mutagenesis identified two regions in the carboxy-terminal portion of the
      TMD that eliminated the Golgi complex localization of the chimeric CD4 proteins
      or ORF7b protein. Collectively, these data demonstrate that the Golgi complex
      retention signal of the ORF7b protein resides solely within the TMD.

PMID- 18632860
TI  - Human endogenous retrovirus K (HML-2) elements in the plasma of people with
      lymphoma and breast cancer.
AB  - Actively replicating endogenous retroviruses entered the human genome millions of
      years ago and became a stable part of the inherited genetic material. They
      subsequently acquired multiple mutations, leading to the assumption that these
      viruses no longer replicate. However, certain human tumor cell lines have been
      shown to release endogenous retroviral particles. Here we show that RNA from
      human endogenous retrovirus K (HERV-K) (HML-2), a relatively recent entrant into
      the human genome, can be found in very high titers in the plasma of patients with
      lymphomas and breast cancer as measured by either reverse transcriptase PCR or
      nucleic acid sequence-based amplification. Further, these titers drop
      dramatically with cancer treatment. We also demonstrate the presence of reverse
      transcriptase and viral RNA in plasma fractions that contain both immature and
      correctly processed HERV-K (HML-2) Gag and envelope proteins. Finally, using
      immunoelectron microscopy, we show the presence of HERV-K (HML-2) virus-like
      particles in the plasma of lymphoma patients. Taken together, these findings
      demonstrate that elements of the endogenous retrovirus HERV-K (HML-2) can be
      found in the blood of modern-day humans with certain cancers.

PMID- 18632861
TI  - The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in
      complex with its protein primer VPg confirms the existence of a second VPg
      binding site on Picornaviridae polymerases.
AB  - The RNA-dependent RNA polymerase (RdRp) is a central piece in the replication
      machinery of RNA viruses. In picornaviruses this essential RdRp activity also
      uridylates the VPg peptide, which then serves as a primer for RNA synthesis.
      Previous genetic, binding, and biochemical data have identified a VPg binding
      site on poliovirus RdRp and have shown that is was implicated in VPg uridylation.
      More recent structural studies have identified a topologically distinct site on
      the closely related foot-and-mouth disease virus RdRp supposed to be the actual
      VPg-primer-binding site. Here, we report the crystal structure at 2.5-A
      resolution of active coxsackievirus B3 RdRp (also named 3D(pol)) in a complex
      with VPg and a pyrophosphate. The pyrophosphate is situated in the active-site
      cavity, occupying a putative binding site either for the coproduct of the
      reaction or an incoming NTP. VPg is bound at the base of the thumb subdomain,
      providing first structural evidence for the VPg binding site previously
      identified by genetic and biochemical methods. The binding mode of VPg to CVB3
      3D(pol) at this site excludes its uridylation by the carrier 3D(pol). We suggest
      that VPg at this position is either uridylated by another 3D(pol) molecule or
      that it plays a stabilizing role within the uridylation complex. The CVB3
      3D(pol)/VPg complex structure is expected to contribute to the understanding of
      the multicomponent VPg-uridylation complex essential for the initiation of genome
      replication of picornaviruses.

PMID- 18632862
TI  - Crystal structure of coxsackievirus B3 3Dpol highlights the functional importance
      of residue 5 in picornavirus polymerases.
AB  - The crystal structure of the coxsackievirus B3 polymerase has been solved at 2.25
      A resolution and is shown to be highly homologous to polymerases from poliovirus,
      rhinovirus, and foot-and-mouth disease viruses. Together, these structures
      highlight several conserved structural elements in picornaviral polymerases,
      including a proteolytic activation-dependent N-terminal structure that is
      essential for full activity. Interestingly, a comparison of all of the
      picornaviral polymerase structures shows an unusual conformation for residue 5,
      which is always located at a distortion in the beta-strand composed of residues 1
      to 8. In our earlier structure of the poliovirus polymerase, we attributed this
      conformation to a crystal packing artifact, but the observation that this
      conformation is conserved among picornaviruses led us to examine the role of this
      residue in further detail. Here we use coxsackievirus polymerase to show that
      elongation activity correlates with the hydrophobicity of residue 5 and,
      surprisingly, more hydrophobic residues result in higher activity. Based on
      structural analysis, we propose that this residue becomes buried during the
      nucleotide repositioning step that occurs prior to phosphoryl transfer. We
      present a model in which the buried N terminus observed in all picornaviral
      polymerases is essential for stabilizing the structure during this conformational
      change.

PMID- 18632863
TI  - Scrapie resistance in ARQ sheep.
AB  - Variation in the ovine prion protein amino acid sequence influences scrapie
      progression, with sheep homozygous for A(136)R(154)Q(171) considered susceptible.
      This study examined the association of survival time of scrapie-exposed ARQ sheep
      with variation elsewhere in the ovine prion gene. Four single nucleotide
      polymorphism alleles were associated with prolonged survival. One nonsynonymous
      allele (T112) was associated with an additional 687 days of survival for scrapie
      exposed sheep compared to M112 sheep (odds ratio, 42.5; P = 0.00014). The only
      two sheep homozygous for T112 (TARQ) did not develop scrapie, suggesting that the
      allelic effect may be additive. These results provide evidence that TARQ sheep
      are genetically resistant to development of classical scrapie.

PMID- 18632864
TI  - Leader of the capsid protein in feline calicivirus promotes replication of
      Norwalk virus in cell culture.
AB  - The inability to grow human noroviruses in cell culture has greatly impeded the
      studies of their pathogenesis and immunity. Vesiviruses, in the family
      Caliciviridae, grow efficiently in cell culture and encode a unique protein in
      the subgenomic region designated as leader of the capsid protein (LC). We
      hypothesized that LC might be associated with the efficient replication of
      vesiviruses in cell culture and promote the replication of human norovirus in
      cells. To test this hypothesis, a recombinant plasmid was engineered in which the
      LC region of feline calicivirus (FCV) was placed under the control of the
      cytomegalovirus promoter (pCI-LC) so that the LC protein could be provided in
      trans to replicating calicivirus genomes bearing a reporter gene. We constructed
      pNV-GFP, a recombinant plasmid containing a full-length NV genome with a green
      fluorescent protein (GFP) in the place of VP1. The transfection of pNV-GFP in MVA
      T7-infected cells produced few GFP-positive cells detected by fluorescence
      microscopy and flow cytometry analysis. When pNV-GFP was cotransfected with pCI
      LC in MVA-T7-infected cells, we observed an increase in the number of GFP
      positive cells (ca. 3% of the whole-cell population). Using this cotransfection
      method with mutagenesis study, we identified potential cis-acting elements at the
      start of subgenomic RNA and the 3' end of NV genome for the virus replication. We
      conclude that LC may be a viral factor which promotes the replication of NV in
      cells, which could provide a clue to growing the fastidious human noroviruses in
      cell culture.

PMID- 18632865
TI  - Enzootic nasal tumor virus envelope requires a very acidic pH for fusion
      activation and infection.
AB  - Enzootic nasal tumor virus (ENTV) is a close relative of jaagsiekte sheep
      retrovirus (JSRV), and the two viruses use the same receptor, hyaluronidase 2
      (Hyal2), for cell entry. We report here that, unlike the JSRV envelope (Env)
      protein, the ENTV Env protein does not induce cell fusion at pHs of 5.0 and above
      but requires a much lower pH (4.0 to 4.5) for fusion to occur. The entry of ENTV
      Env pseudovirions was substantially inhibited by bafilomycin A1 (BafA1) but was
      surprisingly enhanced by lysosomotropic agents and lysosomal protease inhibitors
      following a 4- to 6-h treatment period; of note, prolonged treatment with BafA1
      or ammonium chloride completely blocked ENTV entry. Unlike typical pH-dependent
      viruses, ENTV Env pseudovirions were virtually resistant to inactivation at a low
      pH (4.5 or 5.0). Using chimeras formed from ENTV and JSRV Env proteins, we
      demonstrated that the transmembrane (TM) subunit of ENTV Env is primarily
      responsible for its unusually low pH requirement for fusion but found that the
      surface (SU) subunit of ENTV Env also critically influences its relatively low
      and pH-dependent fusion activity. Furthermore, the poor infectivity of ENTV
      pseudovirions in human cells was significantly improved by either replacing the
      SU subunit of ENTV Env with that of JSRV Env or overexpressing the functional
      Hyal2 receptor in target cells, suggesting that ENTV SU-Hyal2 interaction is
      likely to be the limiting step for viral infectivity. Collectively, our data
      reveal that the fusogenicity of ENTV Env is intrinsically lower than that of JSRV
      Env and that ENTV requires a more acidic pH for fusion, which may occur in an
      intracellular compartment(s) distinct from that used by JSRV.

PMID- 18632866
TI  - Functional homologies between avian and human alphaherpesvirus VP22 proteins in
      cell-to-cell spreading as revealed by a new cis-complementation assay.
AB  - VP22, encoded by the UL49 gene of Marek's disease virus (MDV), is indispensable
      for virus cell-to-cell spreading. We show herein that MDV UL49 can be
      functionally replaced with avian and human viral orthologs. Replacement of MDV
      VP22 with that of avian gallid herpesvirus 3 or herpesvirus of turkey, whose
      residue identity with MDV is close to 60%, resulted in 73 and 131% changes in
      viral spreading, respectively. In contrast, VP22 replacement with human herpes
      simplex virus type 1 resulted in 14% plaque formation. Therefore, heterologous
      avian and human VP22 proteins share sufficient structural homology to support MDV
      cell-to-cell spreading, albeit with different efficiencies.

PMID- 18632867
TI  - Llama-derived single-chain antibody fragments directed to rotavirus VP6 protein
      possess broad neutralizing activity in vitro and confer protection against
      diarrhea in mice.
AB  - Group A rotavirus is one of the most common causes of severe diarrhea in human
      infants and newborn animals. Rotavirus virions are triple-layered particles. The
      outer capsid proteins VP4 and VP7 are highly variable and represent the major
      neutralizing antigens. The inner capsid protein VP6 is conserved among group A
      rotaviruses, is highly immunogenic, and is the target antigen of most
      immunodiagnosis tests. Llama-derived single-chain antibody fragments (VHH) are
      the smallest molecules with antigen-binding capacity and can therefore be
      expected to have properties different from conventional antibodies. In this study
      a library containing the VHH genes of a llama immunized with recombinant inner
      capsid protein VP6 was generated. Binders directed to VP6, in its native
      conformation within the viral particle, were selected and characterized. Four
      selected VHH directed to conformational epitopes of VP6 recognized all human and
      animal rotavirus strains tested and could be engineered for their use in
      immunodiagnostic tests for group A rotavirus detection. Three of the four VHH
      neutralized rotavirus in vivo independently of the strain serotype. Furthermore,
      this result was confirmed by in vivo partial protection against rotavirus
      challenge in a neonatal mouse model. The present study demonstrates for the first
      time a broad neutralization activity of VP6 specific VHH in vitro and in vivo.
      Neutralizing VHH directed to VP6 promise to become an essential tool for the
      prevention and treatment of rotavirus diarrhea.

PMID- 18632868
TI  - Matrix metalloproteinase 9 facilitates West Nile virus entry into the brain.
AB  - West Nile virus (WNV) is the most-common cause of mosquito-borne encephalitis in
      the United States. Invasion of the brain by WNV is influenced by viral and host
      factors, and the molecular mechanism underlying disruption of the blood-brain
      barrier is likely multifactorial. Here we show that matrix metalloproteinase 9
      (MMP9) is involved in WNV entry into the brain by enhancing blood-brain barrier
      permeability. Murine MMP9 expression was induced in the circulation shortly after
      WNV infection, and the protein levels remained high even when viremia subsided.
      In the murine brain, MMP9 expression and its enzymatic activity were upregulated
      and MMP9 was shown to partly localize to the blood vessels. Interestingly, we
      also found that cerebrospinal fluid from patients suffering from WNV contained
      increased MMP9 levels. The peripheral viremia and expression of host cytokines
      were not altered in MMP9(-/-) mice; however, these animals were protected from
      lethal WNV challenge. The resistance of MMP9(-/-) mice to WNV infection
      correlated with an intact blood-brain barrier since immunoglobulin G, Evans blue
      leakage into brain, and type IV collagen degradation were markedly reduced in the
      MMP9(-/-) mice compared with their levels in controls. Consistent with this, the
      brain viral loads, selected inflammatory cytokines, and leukocyte infiltrates
      were significantly reduced in the MMP9(-/-) mice compared to their levels in wild
      type mice. These data suggest that MMP9 plays a role in mediating WNV entry into
      the central nervous system and that strategies to interrupt this process may
      influence the course of West Nile encephalitis.

PMID- 18632869
TI  - Identification of an arginine-rich motif in human papillomavirus type 1 E1;E4
      protein necessary for E4-mediated inhibition of cellular DNA synthesis in vitro
      and in cells.
AB  - Productive infections by human papillomaviruses (HPVs) are restricted to
      nondividing, differentiated keratinocytes. HPV early proteins E6 and E7
      deregulate cell cycle progression and activate the host cell DNA replication
      machinery in these cells, changes essential for virus synthesis. Productive virus
      replication is accompanied by abundant expression of the HPV E4 protein.
      Expression of HPV1 E4 in cells is known to activate cell cycle checkpoints,
      inhibiting G(2)-to-M transition of the cell cycle and also suppressing entry of
      cells into S phase. We report here that the HPV1 E4 protein, in the presence of a
      soluble form of the replication-licensing factor (RLF) Cdc6, inhibits initiation
      of cellular DNA replication in a mammalian cell-free DNA replication system.
      Chromatin-binding studies show that E4 blocks replication initiation in vitro by
      preventing loading of the RLFs Mcm2 and Mcm7 onto chromatin. HPV1 E4-mediated
      replication inhibition in vitro and suppression of entry of HPV1 E4-expressing
      cells into S phase are both abrogated upon alanine replacement of arginine 45 in
      the full-length E4 protein (E1;E4), implying that these two HPV1 E4 functions are
      linked. We hypothesize that HPV1 E4 inhibits competing host cell DNA synthesis in
      replication-activated suprabasal keratinocytes by suppressing licensing of
      cellular replication origins, thus modifying the phenotype of the infected cell
      in favor of viral genome amplification.

PMID- 18632870
TI  - Genomic analysis reveals age-dependent innate immune responses to severe acute
      respiratory syndrome coronavirus.
AB  - The relationship between immunosenescence and the host response to virus
      infection is poorly understood at the molecular level. Two different patterns of
      pulmonary host responses to virus were observed when gene expression profiles
      from severe acute respiratory syndrome coronavirus (SARS-CoV)-infected young mice
      that show minimal disease were compared to those from SARS-CoV-infected aged mice
      that develop pneumonitis. In young mice, genes related to cellular development,
      cell growth, and cell cycle were downregulated during peak viral replication, and
      these transcripts returned to basal levels as virus was cleared. In contrast,
      aged mice had a greater number of upregulated immune response and cell-to-cell
      signaling genes, and the expression of many genes was sustained even after viral
      clearance, suggesting an exacerbated host response to virus. Interestingly, in
      SARS-CoV-infected aged mice, a subset of genes, including Tnfa, Il6, Ccl2, Ccl3,
      Cxcl10, and Ifng, was induced in a biphasic pattern that correlated with peak
      viral replication and a subsequent influx of lymphocytes and severe
      histopathologic changes in the lungs. We provide insight into gene expression
      profiles and molecular signatures underlying immunosenescence in the context of
      the host response to viral infection.

PMID- 18632871
TI  - The interaction between human papillomavirus type 16 and FADD is mediated by a
      novel E6 binding domain.
AB  - High-risk strains of human papillomavirus, such as types 16 and 18, have been
      etiologically linked to cervical cancer. Most cervical cancer tissues are
      positive for both the E6 and E7 oncoproteins, since it is their cooperation that
      results in successful transformation and immortalization of infected cells. We
      have reported that E6 binds to tumor necrosis factor receptor 1 and to Fas
      associated death domain (FADD) and, in doing so, prevents E6-expressing cells
      from responding to apoptotic stimuli. The binding site of E6 to FADD localizes to
      the first 23 amino acids of FADD and has now been further characterized by the
      use of deletion and site-directed mutants of FADD in pull-down and functional
      assays. The results from these experiments revealed that mutations of serine 16,
      serine 18, and leucine 20 obstruct FADD binding to E6, suggesting that these
      residues are part of the E6 binding domain on FADD. Because FADD does not contain
      the two previously identified E6 binding motifs, the LxxphiLsh motif, and the PDZ
      motif, a novel binding domain for E6 has been identified on FADD. Furthermore,
      peptides that correspond to this region can block E6/FADD binding in vitro and
      can resensitize E6-expressing cells to apoptotic stimuli in vivo. These results
      demonstrate the existence of a novel E6 binding domain.

PMID- 18632872
TI  - Functional characterization of Tn1331 gene cassettes.
AB  - OBJECTIVES: The transposon Tn1331 possesses a region including three antibiotic
      resistance genes with the structure aac(6')-Ib-attC-aadA1-attI1*-bla(OXA-9)-attC,
      which potentially includes four gene cassettes. Experimental data on the mobility
      of fusion cassettes as well as those on mobility of cassettes in a genetic
      environment such as Tn1331, which lacks an integrase gene, are limited.
      Therefore, experiments using pJHCMW1, a plasmid harbouring this transposon, in
      the presence of IntI1 supplied in trans were carried out to define which
      cassettes are mobile in vivo. METHODS: In vivo excision of resistance genes was
      investigated in Escherichia coli cells harbouring pJHCMW1 and in a recombinant
      clone that included the intI1 gene under the control of the P(tac) promoter.
      Plasmid DNA was purified and subjected to PCR analysis, and DNA sequencing of PCR
      products was performed to determine whether excision had occurred. RESULTS AND
      CONCLUSIONS: In vivo recombination experiments showed that the fused aadA1-attI1*
      bla(OXA-9)-attC gene cassette was excised in the presence of IntI1. The excision
      of a DNA fragment including aadA1-attI1* was also detected but at a lower
      frequency. The analysis of the latter recombination reaction showed that,
      although attI1* includes only a small fraction of the complete attI1 sequence, it
      is still used as a substrate by IntI1, albeit in a very inefficient manner.

PMID- 18632873
TI  - The pathology of the ulnar nerve in acromegaly.
AB  - CONTEXT: Acromegalic patients may complain of sensory disturbances in their
      hands. Cubital tunnel syndrome, the ulnar nerve neuropathy at the cubital tunnel
      (UCT), in acromegalic patients has never been reported. OBJECTIVE: To describe
      and assess the prevalence of UCT in acromegalic patients and the effects of 1
      year of therapy on UCT. PATIENTS: We examined prospectively 37 acromegalic
      patients with no history of polyneuropathy, acute trauma at the elbow, no
      diabetes or hypothyroidism with clinical examination, nerve conduction studies
      (NCS), and high-resolution ultrasound (US). A control group was made by 50
      volunteers. The local ethics committee approved the study and written informed
      consent was obtained from all subjects involved in the study. INTERVENTION:
      Clinical history, physical examination, NCS, and US were used to diagnose UCT at
      the beginning of the study and after 1 year. RESULTS: In 8 of 37 patients, a
      diagnosis of UCT was made at the beginning of the study reflecting a prevalence
      of 21%. After 1 year, 5 of 8 (62.5%) patients reported clinical and NCS
      improvements and evident US reduction of nerve cross-sectional area (CSA; 16.7+/
      2.9 mm(2) vs 12.2+/-3.1 mm(2); P<0.001). In 3 of 8 (37.5%) patients, the UCT was
      unchanged. Ulnar nerve CSA was significantly increased in acromegalic patients
      with UCT (16.7+/-2.9 mm(2) vs 11.1+/-2.3 mm(2); P<0.047). CONCLUSION: Ulnar
      neuropathy could occur in acromegalic patients and can improve in 62% of cases
      with disease control. Due to the different management and therapeutic approach,
      it would be important to make differential diagnosis between cubital and carpal
      tunnel syndrome in acromegaly.

PMID- 18632874
TI  - Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI
      182 780 on gene expression in the murine uterus.
AB  - Selective estrogen receptor modulators (SERMs) are potentially useful in treating
      various endometrial disorders, including endometrial cancer, as they block some
      of the detrimental effects of estrogen. It remains unclear whether each SERM
      regulates a unique subset of genes and, if so, whether the combination of a SERM
      and 17beta-estradiol has an additive or synergistic effect on gene expression. We
      performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer
      arrays to determine gene expression changes in uteri of ovariectomized mice
      treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI
      182 780, raloxifene, and combinations of high dose of estradiol with one of the
      SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered
      into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low
      dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene +
      estradiol in the second group. Surprisingly, combining a high dose of estradiol
      with a SERM markedly increased (P<0.02) the number of regulated genes compared
      with each individual treatment. Analysis of expression for selected genes in
      uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally
      supported the microarray results. For some cancer-associated genes, including
      Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol
      resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI
      182 780 suppressed more genes governing DNA replication compared with MPP and
      raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and
      raloxifene to treat estrogen-induced endometrial cancer in women.

PMID- 18632875
TI  - Reapprasial of the role of endocrine therapy in meningioma management.
AB  - Recurrent meningiomas constitute an uncommon but significant problem after
      standard therapy failure. Speculation that meningiomas may be subject to
      endocrine influence was supported by both immunohistochemical analyses and
      epidemiological data. Therefore, alternative strategies such as endocrine therapy
      have been suggested. Although evidence of consistent findings for the role of
      specific hormonal exposures is mounting, there are numerous discrepancies about
      the mitogenic effect of hormonal manipulation on meningioma cells. A better
      understanding of the molecular mechanisms involved in meningioma pathogenesis may
      not only lead to the identification of novel diagnostic and prognostic markers
      but may also facilitate the development of new pathogenesis-based targeted
      strategies. This review of literature aims to summarize the present state of the
      art of endocrine therapy in the management of meningiomas, in order to establish
      whether hormonotherapy could be included in the therapeutic strategy for
      unresectable and/or progressive tumours in previously irradiated meningioma
      patients.

PMID- 18632876
TI  - Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation
      with nuclear translocation of beta-catenin and chromosomal instability.
AB  - The role of Wnt pathway in digestive endocrine tumours is debated. The aim of
      this work is to investigate key players in Wnt pathway by a multimodal approach.
      Sixty cases (49 well-differentiated and 11 poorly differentiated) were
      investigated for methylation of adenomatous polyposis coli (APC) and E-cadherin
      promoters, the loss of heterozygosity (LOH) at APC locus and beta-catenin and E
      cadherin expression by immunohistochemistry. Tumours showing altered beta-catenin
      localization were tested for beta-catenin and APC mutations. APC promoter
      methylation was restricted to gastroduodenal tumours (21 out of 59, 36%),
      prevalent in poorly differentiated carcinomas (P=0.042) and correlating with
      aggressive features (high histology grade, P<0.02; tumour death, P=0.026; high
      fractional allelic loss, P=0.002, in turn correlating with short survival,
      P=0.017). LOH at APC locus was found in 14 out of 53 cases (26%, 10
      gastroduodenal and 4 colorectal), prevalent in poorly differentiated carcinomas
      (P=0.002) and correlating with histology grade (P=0.012). beta-catenin abnormal
      expression was found in 41 out of 54 cases (76%), with nuclear staining
      correlating with APC alteration (P=0.047) and short survival (P=0.006). APC, but
      not beta-catenin, gene mutations were found (7 out of 35 tumours), 4 of which in
      the midgut. E-cadherin promoter methylation was rarely detected (2 out of 52
      cases), with cytoplasmic expression in 18 out of 43 cases (42%), not correlating
      with any clinico-pathological feature. In conclusion, Wnt pathway alterations, as
      represented by abnormal beta-catenin localization, are common events in digestive
      endocrine tumours, but only nuclear expression correlates with tumour
      aggressiveness. Though with different alteration mechanisms according to
      anatomical site, APC plays a major role in Wnt pathway activation and in
      determining the high chromosomal instability observed in aggressive endocrine
      carcinomas.

PMID- 18632877
TI  - Expanding participation in Alzheimer's association Safe Return by improving
      enrollment.
AB  - Every adult with a diagnosis of progressive dementia is at risk for wandering
      away or becoming lost. Those with dementia may not have the capacity to remember
      crucial contact information or recognize an unsafe situation, so enrollment in a
      program like Alzheimer's Association Safe Return is crucial. One facility-level
      enrollment plan at the James A. Haley Veterans Hospital in Florida has had a
      relatively high participation rate. A mailed survey was used to help evaluate
      that enrollment process and the results are described here. Of 262 respondents to
      the survey, 193 (74%) indicated the person with dementia enrolled in Safe Return.
      Potential enrollees need the following facilitators: perception of an unsafe
      situation, financial support and easy processing. Safe Return is not just focused
      on those who wander but is essential for all persons with dementia as these
      individuals can become lost in the course of normal daily activities.

PMID- 18632878
TI  - Dynamic coding of vertical facilitated vergence by premotor saccadic burst
      neurons.
AB  - To redirect our gaze in three-dimensional space we frequently combine saccades
      and vergence. These eye movements, known as disconjugate saccades, are
      characterized by eyes rotating by different amounts, with markedly different
      dynamics, and occur whenever gaze is shifted between near and far objects. How
      the brain ensures the precise control of binocular positioning remains
      controversial. It has been proposed that the traditionally assumed "conjugate"
      saccadic premotor pathway does not encode conjugate commands but rather encodes
      monocular commands for the right or left eye during saccades. Here, we directly
      test this proposal by recording from the premotor neurons of the horizontal
      saccade generator during a dissociation task that required a vergence but no
      horizontal conjugate saccadic command. Specifically, saccadic burst neurons
      (SBNs) in the paramedian pontine reticular formation were recorded while rhesus
      monkeys made vertical saccades made between near and far targets. During this
      task, we first show that peak vergence velocities were enhanced to saccade-like
      speeds (e.g., >150 vs. <100 degrees/s during saccade-free movements for
      comparable changes in vergence angle). We then quantified the discharge dynamics
      of SBNs during these movements and found that the majority of the neurons
      preferentially encode the velocity of the ipsilateral eye. Notably, a given
      neuron typically encoded the movement of the same eye during horizontal saccades
      that were made in depth. Taken together, our findings demonstrate that the brain
      stem saccadic burst generator encodes integrated conjugate and vergence commands,
      thus providing strong evidence for the proposal that the classic saccadic
      premotor pathway controls gaze in three-dimensional space.

PMID- 18632879
TI  - Control of neuronal persistent activity by voltage-dependent dendritic
      properties.
AB  - Neural integrators and working memory rely on persistent activity, a widespread
      neural phenomenon potentially involving persistent sodium conductances. Using a
      unique combination of voltage-clamp, dynamic-clamp, and frequency-domain
      techniques, we have investigated the role of voltage-dependent conductances on
      the dendritic electrotonic structure of neurons of the prepositus hypoglossi
      nucleus (PHN), which is known to be involved in oculomotor integration. The PHN
      contains two main neuronal populations: type B neurons with a double
      afterhyperpolarization and type D neurons, which not only are oscillatory but
      also have a greater electrotonic length than that of type B neurons. The
      persistent sodium conductance is present in all PHN neurons, although its effect
      on the dynamic electrotonic structure is shown to significantly differ in the two
      major cell types present in the nucleus. The electrotonic differences are such
      that the persistent sodium conductance can be almost perfectly manipulated in a
      type B neuron using an on-line dynamic clamp to add or subtract virtual sodium
      ion channels. The dynamic-clamp results are confirmed by data-fitted models,
      which suggest that the persistent sodium conductance has two different roles
      depending on its somatic versus dendritic location: perisomatic conductances
      could play a major role in maintaining action potential discharge and dendritic
      conductances would be more involved in other computational properties, such as
      those involving remote synaptic processing or bistable events.

PMID- 18632880
TI  - Gaze behavior when reaching to remembered targets.
AB  - People naturally direct their gaze to visible hand movement goals. Doing so
      improves reach accuracy through use of signals related to gaze position and
      visual feedback of the hand. Here, we studied where people naturally look when
      acting on remembered target locations. Four targets were presented on a screen,
      in peripheral vision, while participants fixed a central cross (encoding phase).
      Four seconds later, participants used a pen to mark the remembered locations
      while free to look wherever they wished (recall phase). Visual references,
      including the screen and the cross, were present throughout. During recall,
      participants neither looked at the marked locations nor prevented eye movements.
      Instead, gaze behavior was erratic and was comprised of gaze shifts loosely
      coupled in time and space with hand movements. To examine whether eye and hand
      movements during encoding affected gaze behavior during recall, in additional
      encoding conditions, participants marked the visible targets with either free
      gaze or with central cross fixation or just looked at the targets. All encoding
      conditions yielded similar erratic gaze behavior during recall. Furthermore,
      encoding mode did not influence recall performance, suggesting that participants,
      during recall, did not exploit sensorimotor memories related to hand and gaze
      movements during encoding. Finally, we recorded a similar lose coupling between
      hand and eye movements during an object manipulation task performed in darkness
      after participants had viewed the task environment. We conclude that acting on
      remembered versus visible targets can engage fundamentally different control
      strategies, with gaze largely decoupled from movement goals during memory-guided
      actions.

PMID- 18632881
TI  - Functional connectivity in the pontomedullary respiratory network.
AB  - Current models propose that a neuronal network in the ventrolateral medulla
      generates the basic respiratory rhythm and that this ventrolateral respiratory
      column (VRC) is profoundly influenced by the neurons of the pontine respiratory
      group (PRG). However, functional connectivity among PRG and VRC neurons is poorly
      understood. This study addressed four model-based hypotheses: 1) the respiratory
      modulation of PRG neuron populations reflects paucisynaptic actions of multiple
      VRC populations; 2) functional connections among PRG neurons shape and coordinate
      their respiratory-modulated activities; 3) the PRG acts on multiple VRC
      populations, contributing to phase-switching; and 4) neurons with no respiratory
      modulation located in close proximity to the VRC and PRG have widely distributed
      actions on respiratory-modulated cells. Two arrays of microelectrodes with
      individual depth adjustment were used to record sets of spike trains from a total
      of 145 PRG and 282 VRC neurons in 10 decerebrate, vagotomized, neuromuscularly
      blocked, ventilated cats. Data were evaluated for respiratory modulation with
      respect to efferent phrenic motoneuron activity and short-timescale correlations
      indicative of paucisynaptic functional connectivity using cross-correlation
      analysis and the "gravity" method. Correlogram features were found for 109 (3%)
      of the 3,218 pairs composed of a PRG and a VRC neuron, 126 (12%) of the 1,043 PRG
      PRG pairs, and 319 (7%) of the 4,340 VRC-VRC neuron pairs evaluated. Correlation
      linkage maps generated for the data support our four motivating hypotheses and
      suggest network mechanisms for proposed modulatory functions of the PRG.

PMID- 18632883
TI  - Heterogeneous neuronal responses to frequency-modulated tones in the primary
      auditory cortex of awake cats.
AB  - Previous studies in anesthetized animals reported that the primary auditory
      cortex (A1) showed homogenous phasic responses to FM tones, namely a transient
      response to a particular instantaneous frequency when FM sweeps traversed a
      neuron's tone-evoked receptive field (TRF). Here, in awake cats, we report that
      A1 cells exhibit heterogeneous FM responses, consisting of three patterns. The
      first is continuous firing when a slow FM sweep traverses the receptive field of
      a cell with a sustained tonal response. The duration and amplitude of FM response
      decrease with increasing sweep speed. The second pattern is transient firing
      corresponding to the cell's phasic tonal response. This response could be evoked
      only by a fast FM sweep through the cell's TRF, suggesting a preference for fast
      FM. The third pattern was associated with the off response to pure tones and was
      composed of several discrete response peaks during slow FM stimulus. These peaks
      were not predictable from the cell's tonal response but reliably reflected the
      time when FM swept across specific frequencies. Our A1 samples often exhibited a
      complex response pattern, combining two or three of the basic patterns above,
      resulting in a heterogeneous response population. The diversity of FM responses
      suggests that A1 use multiple mechanisms to fully represent the whole range of FM
      parameters, including frequency extent, sweep speed, and direction.

PMID- 18632882
TI  - Parvalbumin-positive basket interneurons in monkey and rat prefrontal cortex.
AB  - Differences in the developmental origin and relative proportions of biochemically
      distinct classes of cortical neurons have been found between rodents and
      primates. In addition, species differences in the properties of certain cell
      types, such as neurogliaform cells, have also been reported. Consequently, in
      this study we compared the anatomical and physiological properties of parvalbumin
      (PV)-positive basket interneurons in the prefrontal cortex of macaque monkeys and
      rats. The somal size, total dendritic length, and horizontal and vertical spans
      of the axonal arbor were similar in monkeys and rats. Physiologically, PV basket
      cells could be identified as fast-spiking interneurons in both species, based on
      their short spike and high-frequency firing without adaptation. However,
      important interspecies differences in the intrinsic physiological properties were
      found. In monkeys, basket cells had a higher input resistance and a lower firing
      threshold, and they generated more spikes at near-threshold current intensities
      than those in rats. Thus monkey basket cells appeared to be more excitable. In
      addition, rat basket cells consistently fired the first spike with a substantial
      delay and generated spike trains interrupted by quiescent periods more often than
      monkey basket cells. The frequency of miniature excitatory postsynaptic
      potentials in basket cells was considerably higher in rats than that in monkeys.
      These differences between rats and monkeys in the electrophysiological properties
      of PV-positive basket cells may contribute to the differential patterns of
      neuronal activation observed in rats and monkeys performing working-memory tasks.

PMID- 18632884
TI  - Graded size sensitivity of object-exemplar-evoked activity patterns within human
      LOC subregions.
AB  - A central issue for understanding visual object recognition is how the cortical
      hierarchy represents incoming sensory information and transforms it across
      successive processing stages. The format of object representation in the human
      brain has thus far mostly been studied using adaptation paradigms because the
      neuronal layout of object selectivities was thought to be beyond the resolution
      of conventional functional MRI (fMRI). Recently, however, multivariate pattern
      recognition succeeded in discriminating fMRI responses of object-selective cortex
      to different object exemplars within a given category. Here, we use increased
      spatial fMRI resolution to explore size sensitivity and tolerance to size change
      of response patterns evoked by object exemplars across a range of three sizes.
      Results from Support Vector Classification on responses of the human lateral
      occipital complex (LOC) show that discrimination of size (for a given object) and
      discrimination of objects across changes in size depended on the amount of size
      difference. Even across the largest amount of size change, accuracy for
      generalization was still significant in LOC, whereas the same comparison was at
      chance performance in early visual (calcarine) cortex. Analyzing subregions, we
      further found an anterior-posterior gradient in the degree of size sensitivity
      and size generalization within the posterior-dorsal and anterior-ventral parts of
      LOC. These results speak against fully size-invariant representation of object
      information in human LOC and are hence congruent with findings in monkeys showing
      object identity and size information in population activity of inferotemporal
      cortex. Moreover, these results provide evidence for a fine-grained functional
      heterogeneity within human LOC beyond the commonly used LO/fusiform subdivision.

PMID- 18632885
TI  - Canal and otolith contributions to compensatory tilt responses in pigeons.
AB  - Gaze-stabilizing eye and head responses compensate more effectively for low
      frequency rotational motion when such motion stimulates the otolith organs, as
      during earth-horizontal axis rotations. However, the nature of the otolith signal
      responsible for this improvement in performance has not been previously
      determined. In this study, we used combinations of earth-horizontal axis
      rotational and translational motion to manipulate the magnitude of net linear
      acceleration experienced by pigeons, under both head-fixed and head-free
      conditions. We show that phase enhancement of eye and head responses to low
      frequency rotational motion was causally related to the magnitude of dynamic net
      linear acceleration and not the gravitational acceleration component. We also
      show that canal-driven and otolith-driven eye responses were both spatially and
      temporally appropriate to combine linearly, and that a simple linear model
      combining canal- and otolith-driven components predicted eye responses to complex
      motion that were consistent with our experimental observations. However, the same
      model did not predict the observed head responses, which were spatially but not
      temporally appropriate to combine according to the same linear scheme. These
      results suggest that distinct vestibular processing substrates exist for eye and
      head responses in pigeons and that these are likely different from the vestibular
      processing substrates observed in primates.

PMID- 18632886
TI  - Neuronal responses to moving targets in monkey frontal eye fields.
AB  - Due to delays in visuomotor processing, eye movements directed toward moving
      targets must integrate both target position and velocity to be accurate. It is
      unknown where and how target velocity information is incorporated into the
      planning of rapid (saccadic) eye movements. We recorded the activity of neurons
      in frontal eye fields (FEFs) while monkeys made saccades to stationary and moving
      targets. A substantial fraction of FEF neurons was found to encode not only the
      initial position of a moving target, but the metrics (amplitude and direction) of
      the saccade needed to intercept the target. Many neurons also encoded target
      velocity in a nearly linear manner. The quasi-linear dependence of firing rate on
      target velocity means that the neuronal response can be directly read out to
      compute the future position of a target moving with constant velocity. This is
      demonstrated using a quantitative model in which saccade amplitude is encoded in
      the population response of neurons tuned to retinal target position and modulated
      by target velocity.

PMID- 18632887
TI  - Pitch representations in the auditory nerve: two concurrent complex tones.
AB  - Pitch differences between concurrent sounds are important cues used in auditory
      scene analysis and also play a major role in music perception. To investigate the
      neural codes underlying these perceptual abilities, we recorded from single
      fibers in the cat auditory nerve in response to two concurrent harmonic complex
      tones with missing fundamentals and equal-amplitude harmonics. We investigated
      the efficacy of rate-place and interspike-interval codes to represent both
      pitches of the two tones, which had fundamental frequency (F0) ratios of 15/14 or
      11/9. We relied on the principle of scaling invariance in cochlear mechanics to
      infer the spatiotemporal response patterns to a given stimulus from a series of
      measurements made in a single fiber as a function of F0. Templates created by a
      peripheral auditory model were used to estimate the F0s of double complex tones
      from the inferred distribution of firing rate along the tonotopic axis. This rate
      place representation was accurate for F0s greater, similar900 Hz. Surprisingly,
      rate-based F0 estimates were accurate even when the two-tone mixture contained no
      resolved harmonics, so long as some harmonics were resolved prior to mixing. We
      also extended methods used previously for single complex tones to estimate the
      F0s of concurrent complex tones from interspike-interval distributions pooled
      over the tonotopic axis. The interval-based representation was accurate for F0s
      less, similar900 Hz, where the two-tone mixture contained no resolved harmonics.
      Together, the rate-place and interval-based representations allow accurate pitch
      perception for concurrent sounds over the entire range of human voice and cat
      vocalizations.

PMID- 18632888
TI  - Detecting synfire chain activity using massively parallel spike train recording.
AB  - The synfire chain model has been proposed as the substrate that underlies
      computational processes in the brain and has received extensive theoretical
      study. In this model cortical tissue is composed of a superposition of
      feedforward subnetworks (chains) each capable of transmitting packets of
      synchronized spikes with high reliability. Computations are then carried out by
      interactions of these chains. Experimental evidence for synfire chains has so far
      been limited to inference from detection of a few repeating spatiotemporal
      neuronal firing patterns in multiple single-unit recordings. Demonstration that
      such patterns actually come from synfire activity would require finding a meta
      organization among many detected patterns, as yet an untried approach. In
      contrast we present here a new method that directly visualizes the repetitive
      occurrence of synfire activity even in very large data sets of multiple single
      unit recordings. We achieve reliability and sensitivity by appropriately
      averaging over neuron space (identities) and time. We test the method with data
      from a large-scale balanced recurrent network simulation containing 50 randomly
      activated synfire chains. The sensitivity is high enough to detect synfire chain
      activity in simultaneous single-unit recordings of 100 to 200 neurons from such
      data, enabling application to experimental data in the near future.

PMID- 18632889
TI  - Low-voltage-activated potassium channels underlie the regulation of intrinsic
      firing properties of rat vestibular ganglion cells.
AB  - Individual primary vestibular afferents exhibit spontaneous activity the
      regularity of which can vary from regular to irregular. Different aspects of
      vestibular responsiveness have been associated with this dimension of regularity
      of resting discharge. Isolated rat vestibular ganglion cells (VGCs) showed
      heterogeneous intrinsic firing properties during sustained membrane
      depolarization: some neurons exhibited a strong adaptation generating just a
      single or a few spikes (phasic type), whereas other neurons showed moderate
      adaptation or tonic firing (tonic type). Tonic discharging VGCs were rare at
      postnatal days 5-7 and increased up to approximately 60% of neurons during
      postnatal 2-3 wk. To explore the major factors responsible for the discharge
      regularity of primary vestibular afferents, we investigated the contribution of
      K+ channels to the firing properties of isolated rat VGCs. Phasic firing became
      tonic firing in the presence of 4-aminopyridine or alpha-dendrotoxin, indicating
      that Kv1 potassium channels control the firing pattern of the phasic VGCs.
      Tetraethylammonium decreased the number of spikes during step current stimuli in
      all types. Blockade of Ca2+-activated K+ channels decreased the number of spikes
      in tonic VGCs. Our results suggest that Kv1 channels are critical both in
      determining the pattern of spike discharge in rat vestibular ganglion neurons and
      in their proportional change during maturation.

PMID- 18632890
TI  - Specificity of inferior olive response to stimulus timing.
AB  - The inferior olive is the sole source of the climbing fiber system, one of the
      two major afferent systems of the cerebellum; however, its exact role remains
      unknown. A longstanding hypothesis is that the inferior olive with its unique
      intrinsic rhythmic firing properties mediates motor timing. However, direct
      evidence linking the inferior olive to timing behavior has been difficult to
      demonstrate in animal or human studies likely due to the inhibition of inferior
      olive responses by self-produced movement. Here we used event-related functional
      magnetic resonance imaging (fMRI) and a perceptual task that dissociates the
      temporal from nontemporal attributes of sensory input. Subjects were asked to
      attend to rhythmically occurring identical visual stimuli and to detect a change
      in their timing, spatial orientation, or color. Inferior olive activation was
      seen only when perceiving a change in stimulus timing. These results are
      consistent with animal studies demonstrating that the inferior olive is
      especially sensitive to "unexpected" sensory events and further provide evidence
      supporting the specificity of the inferior olive response to stimulus timing. The
      results are consistent with the view that the inferior olive and the climbing
      fiber system mediate the encoding of temporal information required for both motor
      and nonmotor cognitive processes.

PMID- 18632891
TI  - A novel type of auditory responses: temporal dynamics of 40-Hz steady-state
      responses induced by changes in sound localization.
AB  - Magnetoencephalographic responses to 40-Hz amplitude-modulated tones of 4-s
      duration were recorded in young, middle-aged, and older healthy participants.
      Interaural phase difference (IPD) in the sound carrier was changed during
      stimulus presentation from 0 to 180 degrees , resulting in perceptual change from
      focal to spacious sound. The stimulus modulation elicited synchronized gamma-band
      oscillations, the 40-Hz auditory steady-state response (ASSR). Equivalent current
      dipoles were localized in primary auditory cortices. Waveforms of cortical
      activity showed a decrement in ASSR amplitude 100 ms after stimulus IPD change
      and modification of ASSR phase, which was maximally 90 degrees , corresponding to
      6-ms delay. Time courses of ASSR phase deviation constituted a novel auditory
      response. The amount of ASSR phase change decreased with increasing stimulus
      frequency and revealed upper limits for physiological IPD detection. Thresholds
      for IPD detection were found close to 1,500 Hz in the young, around 1,250 Hz in
      the middle-aged group, and around 1,000 Hz in the older group. Whereas the ASSR
      change response revealed aging-related decline of binaural hearing, the amplitude
      of 40-Hz response and the size of the ASSR change response were not affected by
      aging. Additional ASSR change responses were recorded at a high rate of stimulus
      changes every 400 ms. ASSR response detection at this rate was superior to
      response detection based on the auditory-evoked P1-N1-P2 response. Responses to
      changes from focal to spacious sound were larger than those in the reverse
      direction. The ASSRs were interpreted in relation to oscillatory gamma-band
      activity representing auditory object representation.

PMID- 18632892
TI  - Neurons in the pontomedullary reticular formation signal posture and movement
      both as an integrated behavior and independently.
AB  - We have previously suggested that the discharge characteristics of some neurons
      in the pontomedullary reticular formation (PMRF) are contingent on the
      simultaneous requirement for activity in both ipsilateral flexor muscles and
      contralateral extensors. To test this hypothesis we trained cats to stand on four
      force platforms and to perform a task in which they were required to reach
      forward with one forelimb or the other and depress a lever. As such the task
      required the cat to make a flexion movement followed by an extension in the
      reaching limb while maintaining postural support by increasing extensor muscle
      tonus in the supporting limbs. We recorded the activity of 131 neurons from the
      PMRF of three cats during left, ipsilateral reach. Of these, 86/131 (66%) showed
      a change in discharge frequency prior to the onset of activity in one of the
      prime flexor muscles and 43/86 (50%) showed a bimodal pattern of discharge in
      which activity decreased during the lever press. Among the remaining cells, 28/86
      (33%) showed maintained activity throughout the reach and the lever press. Most
      cells showed a broadly similar pattern of discharge during reaches with the
      right, contralateral limb. We suggest these results support the view that a
      population of neurons within the PMRF contributes to the control of movement in
      one forelimb and the control of posture in the other forelimb as a coordinated
      unit. Another population of neurons contributes to the control of postural
      support independently of the nature of the activity in the reaching limb.

PMID- 18632893
TI  - AMPA receptor-dependent H2O2 generation in striatal medium spiny neurons but not
      dopamine axons: one source of a retrograde signal that can inhibit dopamine
      release.
AB  - Dopamine-glutamate interactions in the striatum are critical for normal basal
      ganglia-mediated control of movement. Although regulation of glutamatergic
      transmission by dopamine is increasingly well understood, regulation of
      dopaminergic transmission by glutamate remains uncertain given the apparent
      absence of ionotropic glutamate receptors on dopaminergic axons in dorsal
      striatum. Indirect evidence suggests glutamatergic regulation of striatal
      dopamine release is mediated by a diffusible messenger, hydrogen peroxide (H2O2),
      generated downstream from glutamatergic AMPA receptors (AMPARs). The mechanism of
      H2O2-dependent inhibition of dopamine release involves activation of ATP
      sensitive K+ (KATP) channels. However, the source of modulatory H2O2 is unknown.
      Here, we used whole cell recording, fluorescence imaging of H2O2, and
      voltammetric detection of evoked dopamine release in guinea pig striatal slices
      to examine contributions from medium spiny neurons (MSNs), the principal neurons
      of striatum, and dopamine axons to AMPAR-dependent H2O2 generation. Imaging
      studies of H2O2 generation in MSNs provide the first demonstration of AMPAR
      dependent H2O2 generation in neurons in the complex brain-cell microenvironment
      of brain slices. Stimulation-induced increases in H2O2 in MSNs were prevented by
      GYKI-52466, an AMPAR antagonist, or catalase, an H2O2 metabolizing enzyme, but
      amplified by mercaptosuccinate (MCS), a glutathione peroxidase inhibitor. By
      contrast, dopamine release evoked by selective stimulation of dopamine axons was
      unaffected by GYKI-52466 or MCS, arguing against dopamine axons as a significant
      source of modulatory H2O2. Together, these findings suggest that glutamatergic
      regulation of dopamine release via AMPARs is mediated through retrograde
      signaling by diffusible H2O2 generated in striatal cells, including medium spiny
      neurons, rather than in dopamine axons.

PMID- 18632894
TI  - Serotonin 1B receptor modulates frequency response curves and spectral
      integration in the inferior colliculus by reducing GABAergic inhibition.
AB  - The selectivity of sensory neurons for stimuli is often shaped by a balance
      between excitatory and inhibitory inputs, making this balance an effective target
      for regulation. In the inferior colliculus (IC), an auditory midbrain nucleus,
      the amplitude and selectivity of frequency response curves are altered by the
      neuromodulator serotonin, but the changes in excitatory-inhibitory balance that
      mediate this plasticity are not well understood. Previous findings suggest that
      the presynaptic 5-HT1B receptor may act to decrease the release of GABA onto IC
      neurons. Here, in vivo extracellular recording and iontophoresis of the selective
      5-HT1B agonist CP93129 were used to characterize inhibition within and
      surrounding frequency response curves using two-tone protocols to indirectly
      measure inhibition as a decrease in spikes relative to an excitatory tone alone.
      The 5-HT1B agonist attenuated such two-tone spike reduction in a varied pattern
      among neurons, suggesting that the function of 5-HT1B modulation also varies. The
      hypothesis that the 5-HT1B receptor reduces inhibition was tested by comparing
      the effects of CP93129 and the GABAA antagonists bicuculline and gabazine in the
      same neurons. The effects of GABAA antagonists on spike count, tuning bandwidth,
      two-tone ratio, and temporal response characteristics mimicked those of CP93129
      across the neuron population. GABAA antagonists also blocked or reduced the
      facilitation of evoked responses by CP93129. These results are all consistent
      with the reduction of GABAA-mediated inhibition by 5-HT1B receptors in the IC,
      resulting in an increase in the level of evoked responses in some neurons, and a
      decrease in spectral selectivity in others.

PMID- 18632895
TI  - Short-term synaptic depression and recovery at the mature mammalian endbulb of
      Held synapse in mice.
AB  - The endbulb of Held synapses between the auditory nerve fibers (ANF) and cochlear
      nucleus bushy neurons convey fine temporal information embedded in the incoming
      acoustic signal. The dynamics of synaptic depression and recovery is a key in
      regulating synaptic transmission at the endbulb synapse. We studied short-term
      synaptic depression and recovery in mature (P22-38) CBA mice with stimulation
      rates that were comparable to sound-driven activities recorded in vivo. Synaptic
      depression in mature mice is less severe ( approximately 40% at 100 Hz) than
      reported for immature animals and the depression is predominately due to
      depletion of releasable vesicles. Recovery from depression depends on the rate of
      activity and accumulation of intracellular Ca2+ at the presynaptic terminal. With
      a regular stimulus train at 100 Hz in 2 mM external [Ca2+], the recovery from
      depletion was slow (tauslow, approximately 2 s). In contrast, a fast (taufast,
      approximately 25 ms), Ca2+-dependent recovery followed by a slower recovery
      (tauslow, approximately 2 s) was seen when stimulus rates or external [Ca2+]
      increased. In normal [Ca2+], recovery from a 100-Hz Poisson-like train is rapid,
      suggesting that Poisson-like trains produce a higher internal [Ca2+] than regular
      trains. Moreover, the fast recovery was slowed by approximately twofold in the
      presence of calmidazolium, a Ca2+/calmodulin inhibitor. Our results suggest that
      endbulb synapses from high spontaneous firing rate auditory nerve fibers normally
      operate in a depressed state. The accelerated synaptic recovery during high rates
      of activity is likely to ensure that reliable synaptic transmission can be
      achieved at the endbulb synapse.

PMID- 18632896
TI  - Neural modulation by regularity and passage of time.
AB  - The current study tested whether multiple rhythms could flexibly induce temporal
      expectations (temporal orienting) and whether these expectations interact with
      temporal expectations associated with the passage of time (foreperiod effects). A
      visual stimulus that moved following a regular rhythm was temporarily occluded
      for a variable duration (occlusion foreperiod). The task involved making a
      speeded perceptual discrimination about the target stimulus that reappeared after
      the occlusion. Temporal-orienting effects were measured by comparing performance
      and event-related potentials on conditions in which the timing for target
      reappearance was predictable (valid) versus unpredictable (invalid) according to
      the rhythm. Foreperiod effects were measured by comparing conditions in which the
      target was occluded for progressively longer periods of time (short, medium, and
      long foreperiods) and hence were increasingly predictable. The results showed
      strong interactions between temporal orienting and foreperiod effects during the
      facilitation of behavior and neural activity associated with late perceptual and
      response selection processes. Temporal orienting attenuated the N2 amplitude and
      decreased the P3 latency only at short foreperiods. Temporal preparation related
      to foreperiod effects abolished temporal orienting effects at medium and long
      foreperiods. Likewise, foreperiod effects attenuated the N1 and N2 amplitudes and
      decreased the P3 latency only in the invalid orienting condition as preparation
      related to temporal orienting abolished foreperiod effects in the valid
      condition. This high degree of neural overlap between the effects of temporal
      orienting driven by rhythms and foreperiod effects associated with the passage of
      time suggests the involvement of a common mechanism for temporal preparation.

PMID- 18632897
TI  - Effect of synaptic connectivity on long-range synchronization of fast cortical
      oscillations.
AB  - Cortical gamma oscillations in the 20- to 80-Hz range are associated with
      attentiveness and sensory perception and have strong connections to both
      cognitive processing and temporal binding of sensory stimuli. These gamma
      oscillations become synchronized within a few milliseconds over distances
      spanning a few millimeters in spite of synaptic delays. In this study using in
      vivo recordings and large-scale cortical network models, we reveal a critical
      role played by the network geometry in achieving precise long-range
      synchronization in the gamma frequency band. Our results indicate that the
      presence of many independent synaptic pathways in a two-dimensional network
      facilitate precise phase synchronization of fast gamma band oscillations with
      nearly zero phase delays between remote network sites. These findings predict a
      common mechanism of precise oscillatory synchronization in neuronal networks.

PMID- 18632899
TI  - Characterization of vancomycin-heteroresistant Staphylococcus aureus from the
      metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007).
AB  - We screened for heteroresistant, vancomycin-intermediate Staphylococcus aureus
      (hVISA) among clinical isolates of methicillin-resistant S. aureus collected from
      three hospitals (two urban teaching hospitals and one community hospital) in the
      Detroit metropolitan area over a 22-year period. The Macro Etest method was used
      to screen all available isolates. Confirmation of hVISA-positive screens were
      confirmed by population-area under the concentration-time curve (AUC) analysis. A
      total of 1,499 isolates revealed hVISA/VISA rates of 2.2/0.4% (n = 225; 1986 to
      1993), 7.6/2.3% (n = 356; 1994 to 2002), and 8.3/0.3% (n = 917; 2003 to 2007).
      Population-AUC analysis confirmed 92.6% of the hVISA-positive strains determined
      by the Macro Etest method. For the isolates with known sources (1,208), the
      predominant source of hVISA was blood (60%), followed by lung (21%), skin and
      wound infections (14%), abscess (1%), and other (4%). The percentage of hVISA
      positive strains appeared to increase as a function of the vancomycin MIC.
      Staphylococcal cassette chromosome mec (SCCmec) typing revealed that the majority
      (56.9%) of the hVISA strains were SCCmec type II and 39.4% were type IV; the
      majority of these strains were collected from 2000 to 2007. Our data indicate
      that the prevalence of hVISA may be increasing. Based on the association of
      vancomycin treatment failure in patients with hVISA, surveillance of hVISA
      strains is warranted.

PMID- 18632900
TI  - Detection of KPC-2 in a clinical isolate of Proteus mirabilis and first reported
      description of carbapenemase resistance caused by a KPC beta-lactamase in P.
      mirabilis.
AB  - An isolate of Proteus mirabilis recovered from blood cultures of a diabetic
      patient was shown to be resistant to imipenem, meropenem, and ertapenem by disk
      diffusion susceptibility testing. Amplification of whole-cell and/or plasmid DNA
      recovered from the isolate with primers specific for the bla(KPC) carbapenemase
      gene produced an amplicon of the expected size which was confirmed to be bla(KPC
      2) by sequence analysis. Transformation of a susceptible Escherichia coli host
      with plasmid preparations from the isolate generated a transformant for which the
      MICs of all of the carbapenems tested were increased three- to fourfold. We
      believe this to be the first report of carbapenem resistance in P. mirabilis
      caused by the acquisition of bla(KPC).

PMID- 18632901
TI  - Two unusual occurrences of trichomoniasis: rapid species identification by PCR.
AB  - PCR analysis in two unusual occurrences of trichomoniasis, trichomonal empyema
      due to Trichomonas tenax and Trichomonas vaginalis in an infant urine sample,
      allowed us to obtain rapid and accurate trichomonad species identification. The
      weak sensitivity of wet preparations and the low viability of the flagellates can
      be remedied by the PCR method.

PMID- 18632902
TI  - Comparison of the Luminex xTAG respiratory viral panel with in-house nucleic acid
      amplification tests for diagnosis of respiratory virus infections.
AB  - Detection of respiratory viruses using sensitive real-time nucleic acid
      amplification tests (NATs) is invaluable for patient and outbreak management.
      However, the wide range of potential respiratory virus pathogens makes testing
      using individual real-time NATs expensive and laborious. The objective of this
      study was to compare the detection of respiratory virus targets using the Luminex
      xTAG respiratory viral panel (RVP) assay with individual real-time NATs used at
      the Provincial Laboratory of Public Health, Calgary, Alberta, Canada. The study
      included 1,530 specimens submitted for diagnosis of respiratory infections from
      December 2006 to May 2007. Direct-fluorescent-antigen-positive nasopharyngeal
      samples were excluded from this study. A total of 690 and 643 positives were
      detected by RVP and in-house NATs, respectively. Kappa correlation between in
      house NATs and RVP for all targets ranged from 0.721 to 1.000. The majority of
      specimens missed by in-house NATs (96.7%) were positive for picornaviruses.
      Samples missed by RVP were mainly positive for adenovirus (51.7%) or respiratory
      syncytial virus (27.5%) by in-house NATs and in general had low viral loads. RVP
      allows for multiplex detection of 20 (and differentiation between 19) respiratory
      virus targets with considerable time and cost savings compared with alternative
      NATs. Although this first version of the RVP assay has lower sensitivity than in
      house NATs for detection of adenovirus, it has good sensitivity for other
      targets. The identification of picornaviruses and coronaviruses and concurrent
      typing of influenza A virus by RVP, which are not currently included in our
      diagnostic testing algorithm, will improve our diagnosis of respiratory tract
      infections.

PMID- 18632903
TI  - Bartonella sp. bacteremia in patients with neurological and neurocognitive
      dysfunction.
AB  - We detected infection with a Bartonella species (B. henselae or B. vinsonii
      subsp. berkhoffii) in blood samples from six immunocompetent patients who
      presented with a chronic neurological or neurocognitive syndrome including
      seizures, ataxia, memory loss, and/or tremors. Each of these patients had
      substantial animal contact or recent arthropod exposure as a potential risk
      factor for Bartonella infection. Additional studies should be performed to
      clarify the potential role of Bartonella spp. as a cause of chronic neurological
      and neurocognitive dysfunction.

PMID- 18632904
TI  - Molecular characterization of human-colonizing Streptococcus agalactiae strains
      isolated from throat, skin, anal margin, and genital body sites.
AB  - Streptococcus agalactiae carriage was evaluated by sampling four body sites in a
      group of 249 healthy individuals including both sexes and a wide range of ages;
      the aims were to study the population structure of colonizing strains by
      multilocus sequence typing (MLST) and to evaluate their diversity by serotyping,
      SmaI macrorestriction analysis, and PCR screening for genetic markers of highly
      virulent clones for neonates. The prevalences of carriage were 27% in women and
      32% in men. The major positive body site was the genital tract (23% in women and
      21% in men); skin, throats, and anal margins were also positive in 2%, 4%, and
      14%, respectively. These human-colonizing strains belonged mostly to serotypes
      III (24%), Ia (21%), V (18%), and Ib (17%). Twenty-three sequence types (STs)
      were identified. The MLST characteristics of the strains isolated from a single
      anatomic site-genital (vagina [women] or from a sample of the first urination
      after arising from a night's sleep [men]), throat, skin, or anal margin-suggest a
      body site colonization specificity for particular STs: strains of STs 2, 10, 19,
      and 196 were isolated only from genital sites; strains of STs 1, 8, and 23 were
      isolated more frequently from throat florae; and strains recovered only from anal
      margin samples were more closely related to strains isolated from throats than to
      those from genital sites. Most strains of STs 1, 8, and 23-STs that are
      increasingly described as being responsible for adult infections-did not carry
      any markers of strains virulent for neonates, suggesting that the virulence of
      these strains is probably associated with other genetic determinants. In
      addition, the genetic diversities of the strains varied between STs: STs 2, 8,
      10, 23, and 196 were the most diverse; STs 1 and 19 were more homogeneous; and ST
      17 strains formed three distant groups.

PMID- 18632905
TI  - Evaluation of four selective agars and two enrichment broths in screening for
      methicillin-resistant Staphylococcus aureus.
AB  - To evaluate methicillin-resistant Staphylococcus aureus detection, we tested in
      vitro four selective agars and two enrichment broths apart and in combination.
      Tryptone soya broth with salt, aztreonam, and cefoxitin appeared to be the most
      sensitive medium. This broth was superior to a phenol red mannitol broth with
      aztreonam and ceftizoxime.

PMID- 18632906
TI  - Genetic lineages of community-associated methicillin-resistant Staphylococcus
      aureus in Kuwait hospitals.
AB  - Twenty-six community-associated methicillin-resistant Staphylococcus aureus
      (CAMSRA) isolates were characterized by pulsed-field gel electrophoresis (PFGE)
      and multilocus sequence typing (MLST) and screened for accessory gene regulator
      (agr), capsular polysaccharide (cap), and Panton-Valentine leucocidin (PVL)
      genes. They exhibited five PFGE patterns (types A to E). The majority were PFGE
      type A (12 isolates) or type B (8 isolates). MLST showed that PFGE type A
      isolates belonged to sequence type 80 (ST80), while the PFGE type B isolates were
      ST30. The ST80 and ST30 clones contained agr allotype 3, cap type 8, and PVL. The
      results showed that two internationally recognized CAMRSA clones are dominant in
      Kuwait hospitals.

PMID- 18632907
TI  - Trends in species distribution and susceptibility of bloodstream isolates of
      Candida collected in Monterrey, Mexico, to seven antifungal agents: results of a
      3-year (2004 to 2007) surveillance study.
AB  - During a 3-year surveillance program (2004 to 2007) in Monterrey, Mexico, 398
      isolates of Candida spp. were collected from five hospitals. We established the
      species distribution and in vitro susceptibilities of these isolates. The species
      included 127 Candida albicans strains, 151 C. parapsilosis strains, 59 C.
      tropicalis strains, 32 C. glabrata strains, 11 C. krusei strains, 5 C.
      guilliermondii strains, 4 C. famata strains, 2 C. utilis strains, 2 C.
      zeylanoides strains, 2 C. rugosa strains, 2 C. lusitaniae strains, and 1 C.
      boidinii strain. The species distribution differed with the age of the patients.
      The proportion of candidemias caused by C. parapsilosis was higher among infants
      <or=1 year old, and the proportion of candidemias caused by C. glabrata increased
      with patient age (>45 years old). MICs were calculated following the criteria of
      the Clinical Laboratory Standards Institute reference broth macrodilution method.
      Overall, C. albicans, C. parapsilosis, and C. tropicalis isolates were
      susceptible to fluconazole and amphotericin B. However, 31.3% of C. glabrata
      isolates were resistant to fluconazole (MIC >or= 64 microg/ml), 43.3% were
      resistant to itraconazole (MIC >or= 1 microg/ml), and 12.5% displayed resistance
      to amphotericin B (MIC >or= 2 microg/ml). Newer triazoles, namely, voriconazole,
      posaconazole, and ravuconazole, had a notable in vitro activity against all
      Candida species tested. Also, caspofungin was active against Candida sp. isolates
      (MIC(90) <or= 0.5 microg/ml) except C. parapsilosis (MIC(90) = 2 microg/ml). It
      is imperative to promote a national-level surveillance program to monitor this
      important microorganism.

PMID- 18632908
TI  - Heart valves should not be routinely cultured.
AB  - Heart valve (HV) culture is one of the major Duke criteria for the diagnosis of
      definite infectious endocarditis (IE). However, previous series suggest that
      heart valve culture does not have good sensitivity (7.8 to 17.6%) and may be
      contaminated during manipulation. Our goal was to establish the value of routine
      cultures of heart valves in patients with and without IE. From 2004 to 2006,
      resected heart valves were systematically cultured according to standard
      procedures. The definition and etiology of IE were based on the Duke criteria and
      on valve PCR of specimens from blood culture-negative patients. Bacterial and
      fungal broad-range PCR was performed. A total of 1,101 heart valves were studied:
      1,030 (93.6%) from patients without IE and 71 (6.4%) from patients with IE (42
      patients). Overall, 321 (29.2%) cultures were positive (28/71 [39.4%] IE cases
      and 293/1,030 [28.4%] non-IE). All IE patients with negative heart valve cultures
      had received antimicrobial therapy. The yield of culture of heart valves for IE
      diagnosis was as follows: sensitivity, 25.4%; specificity, 71.6%; positive
      predictive value (PPV), 5.8%; and negative predictive value, 93.3%. Because of
      its poor sensitivity and PPV, valve cultures should not be performed for patients
      without a clinical suspicion of IE. For patients with confirmed IE, heart valve
      cultures should be interpreted with caution.

PMID- 18632909
TI  - Molecular diagnosis of Saksenaea vasiformis cutaneous infection after scorpion
      sting in an immunocompetent adolescent.
AB  - We report the first case of cutaneous mucormycosis after a scorpion sting in
      Tunisia. Histopathology showed broad aseptate hyphae suggestive of a Zygomycete.
      Saksenaea vasiformis was identified by PCR amplification and sequencing of the
      fungal DNA on a cutaneous biopsy. Successful treatment was obtained by surgery
      and liposomal amphotericin B.

PMID- 18632910
TI  - Acinetobacter baylyi as a pathogen for opportunistic infection.
AB  - There are no previous reports of human infection due to Acinetobacter baylyi. In
      this study, we report on six patients with bacteremia due to A. baylyi, based on
      analysis of the 16S-23S rRNA intergenic spacer and the 16S rRNA gene. All six
      patients had multiple underlying diseases. The infection was nosocomially
      acquired in five patients. The six clinical isolates had similar ribopatterns,
      suggesting a clonal relationship. Compared to the reference strain, the clinical
      isolates were more resistant to antimicrobial agents, especially beta-lactam
      antibiotics. In three of the isolates, they may have undetermined plasmid
      mediated class C type beta-lactamases because of the positive results in a double
      disk synergy test using 3-aminophenylboronic acid. Two of the clinical isolates
      retained a level of natural transformability similar to that of the reference
      strain. None of the patients died, although only three of them received
      appropriate antimicrobial therapy. This study demonstrates that A. baylyi is a
      potential human pathogen that can cause nosocomial infection in immunocompromised
      patients.

PMID- 18632911
TI  - Characterization of Staphylococcus aureus isolates from nasal cultures collected
      from individuals in the United States in 2001 to 2004.
AB  - This study characterizes methicillin-susceptible Staphylococcus aureus (MSSA) and
      methicillin-resistant S. aureus (MRSA) isolates recovered from nasal cultures of
      noninstitutionalized individuals in the United States obtained in 2001 to 2004 as
      part of the National Health and Nutrition Examination Survey. Every tenth MSSA
      isolate and all MRSA isolates were typed by pulsed-field gel electrophoresis
      (PFGE), screened for multiple toxin genes, and tested for susceptibility to 14
      antimicrobial agents. USA200, USA600, and USA900 were the predominant PFGE types
      among MSSA isolates in both the 2001 to 2002 and the 2003 to 2004 time periods,
      although they accounted for only 51.3% of 316 MSSA isolates typed in 2001 and
      2002 and only 43.4% of 237 MSSA isolates typed in 2003 and 2004. In contrast,
      USA100, USA800, and USA700 accounted for 80.0% of the 75 MRSA isolates typed in
      2001 and 2002, while USA100, USA800, and USA300 accounted for 78.4% of 134 MRSA
      isolates typed in 2003 and 2004. The proportion of MRSA isolates that were USA300
      increased significantly from the first to the second time period (P = 0.03). Most
      USA200 isolates (both MSSA and MRSA) carried the gene for toxic shock syndrome
      toxin; however, carriage of the genes encoding Panton-Valentine leukocidin, while
      common among MRSA of PFGE type USA300, was rare among MSSA USA300 in both time
      periods. Most MSSA isolates remained susceptible to all antimicrobial agents
      except erythromycin (79.1 and 76.0% susceptibilities in the 2001 to 2002 and the
      2003 to 2004 periods, respectively). In contrast, the proportions of MRSA
      isolates that were susceptible to chloramphenicol, clindamycin, and erythromycin
      were lower in 2003 and 2004 than in 2001 and 2002, although none of these
      differences was statistically significant.

PMID- 18632912
TI  - Detection and characterization of group C rotaviruses in asymptomatic piglets in
      Ireland.
AB  - Group C rotaviruses are important human enteric pathogens that have also been
      detected in a variety of mammalian species, including pigs. Group C rotaviruses
      have been identified in piglets with diarrhea, but their ecology remains to be
      elucidated. By screening of 292 fecal samples collected from 4- to 5-week-old
      asymptomatic pigs from four herds in Ireland between 2005 and 2007, 13 (4.4%)
      samples tested positive by reverse transcription-PCR for group C rotavirus. Group
      A rotaviruses were also detected in 19 samples but not in conjunction with group
      C viruses. The gene encoding the major group C neutralization antigen, the outer
      capsid protein VP7, was sequenced. The majority of the strains were very closely
      related to each other (>99% amino acid [aa] identity) and were characterized as
      genogroup G1 since they were genetically related to the prototype porcine strain
      Cowden (92.6% aa identity). Conversely, two strains (1GA/05/Cork/Ire and
      281/07/Dublin/Ire) were characterized as genogroup G6 since they displayed the
      highest identity (89.2 to 94.0% aa) to porcine G6 strains (43/06-22-like).
      Unexpectedly, one such G6 strain, 1GA/05/Cork/Ire, lacked the 4-aa insertion in
      the VP7 variable region VR8 found in all the other G6 group C rotaviruses. This
      study provides evidence that porcine group C rotavirus may be detected not
      infrequently in asymptomatic piglets. In addition, it provides evidence that,
      unlike the human viruses, porcine group C rotaviruses display broad genetic
      heterogeneity, which may pose a challenge for the development of prophylactic
      tools.

PMID- 18632913
TI  - Molecular-beacon-based real-time PCR for detection and quantification of
      Mycobacterium tuberculosis DNA in clinical samples.

PMID- 18632914
TI  - Multiplex tandem PCR: a novel platform for rapid detection and identification of
      fungal pathogens from blood culture specimens.
AB  - We describe the first development and evaluation of a rapid multiplex tandem PCR
      (MT-PCR) assay for the detection and identification of fungi directly from blood
      culture specimens that have been flagged as positive. The assay uses a short
      cycle multiplex amplification, followed by 12 simultaneous PCRs which target the
      fungal internal transcribed spacer 1 (ITS1) and ITS2 region, elongation factor 1
      alpha (EF1-alpha), and beta-tubulin genes to identify 11 fungal pathogens:
      Candida albicans, Candida dubliniensis, Candida glabrata, Candida guilliermondii,
      Candida krusei, Candida parapsilosis complex, Candida tropicalis, Cryptococcus
      neoformans complex, Fusarium solani, Fusarium species, and Scedosporium
      prolificans. The presence or absence of a fungal target was confirmed by melting
      curve analysis. Identification by MT-PCR correlated with culture-based
      identification for 44 (100%) patients. No cross-reactivity was detected in 200
      blood culture specimens that contained bacteria or in 30 blood cultures without
      microorganisms. Fungi were correctly identified in five specimens with bacterial
      coinfection and in blood culture samples that were seeded with a mixture of yeast
      cells. The MT-PCR assay was able to provide rapid (<2 h), sensitive, and specific
      simultaneous detection and identification of fungal pathogens directly from blood
      culture specimens.

PMID- 18632915
TI  - Evaluation of CHROMagar KPC for rapid detection of carbapenem-resistant
      Enterobacteriaceae.
AB  - A new CHROMagar KPC medium was compared to MacConkey agar with carbapenem discs
      and PCR for the bla(KPC) gene for rapid detection of carbapenem-resistant
      Klebsiella pneumoniae. The sensitivity and specificity relative to PCR were 100%
      and 98.4%, respectively, for CHROMagar KPC and 92.7% and 95.9%, respectively, for
      MacConkey agar.

PMID- 18632916
TI  - Efficacy of dry mist of hydrogen peroxide (DMHP) against Mycobacterium
      tuberculosis and use of DMHP for routine decontamination of biosafety level 3
      laboratories.
AB  - Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide
      and is becoming a greater concern due to the development of multidrug-resistant
      strains. M. tuberculosis can contaminate rooms, medical equipment, and research
      laboratories and has the propensity to be highly resistant to decontamination.
      The aim of this study was to determine the efficacy of room disinfection with a
      dry mist of hydrogen peroxide (DMHP) in a biosafety level 3 laboratory in the
      event of contamination with M. tuberculosis. The biological indicators (BIs) were
      comprised of presterilized cotton tissues on which amounts of about 10(7) CFU/ml
      of M. tuberculosis H37Ra were dried. The device (Sterinis; Gloster Sante Europe)
      provided a DMHP of 5% hydrogen peroxide during 25 min. Three experiments were
      performed. The viable bacteria were reduced by values of more than 5 log(10), and
      no colony grew from any BI. In conclusion, DMHP shows promise as an effective and
      safe alternative to the currently used formaldehyde.

PMID- 18632917
TI  - Thymidine kinase sequence analysis of herpes simplex virus type 1 strains present
      in different compartments in an atypical impetiginous rash on the lesional skin
      of a burn patient.
AB  - We report the case of a 23-year-old male burn patient with an unusual herpes
      simplex virus (HSV) skin manifestation. The clinical symptoms and results of HSV
      type 1 (HSV-1) UL23 polymorphism analysis from saliva and lesional skin
      underscores the need for performing molecular analysis of HSV-1 infections in
      burned patients presenting unusual skin lesions.

PMID- 18632918
TI  - Levels of soluble CD163 and severity of malaria in children in Ghana.
AB  - CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed
      late in inflammation. It is involved in the haptoglobin-mediated removal of free
      hemoglobin from plasma, has been identified as a naturally soluble plasma
      glycoprotein with potential anti-inflammatory properties, and is possibly linked
      to an individual's haptoglobin phenotype. High levels of soluble CD163 (sCD163)
      in a malaria episode may therefore downregulate inflammation and curb disease
      severity. In order to verify this, the relationships between sCD163 levels,
      malaria severity, and selected inflammatory mediators (tumor necrosis factor
      alpha [TNF-alpha], interleukin-6 [IL-6], and IL-10) were assessed by enzyme
      linked immunosorbent assay using plasma samples obtained from pediatric malaria
      patients with uncomplicated malaria (UM [n = 38]), cerebral malaria (CM [n =
      52]), and severe malarial anemia (SA [n = 55]) during two consecutive malaria
      transmission seasons (2002 and 2003). Median sCD163 levels were higher in UM
      (11.9 microg/ml) patients than in SA (7.7 microg/ml; P = 0.010) and CM (8.0
      microg/ml; P = 0.031) patients. Levels of sCD163 were also higher in all patient
      groups than in a group of 81 age-matched healthy controls. The higher sCD163/TNF
      alpha ratio in UM patients, coupled with the fact that sCD163 levels correlated
      with TNF-alpha levels in UM patients but not in CM and SA patients, suggests
      inflammatory dysregulation in the complicated cases. The study showed that sCD163
      levels are elevated during acute malaria. High sCD163 levels in UM patients may
      be due to the induction of higher-level anti-inflammatory responses, enabling
      them to avoid disease complications. It is also possible that UM patients simply
      lost their CD163 receptors from macrophages in inflammatory sites while
      complicated-malaria patients still had their receptors attached to activated
      macrophages, reflecting ongoing and higher-level inflammation associated with
      complicated malaria.

PMID- 18632919
TI  - Evaluation of a multiplex flow immunoassay for detection of epstein-barr virus
      specific antibodies.
AB  - Conventional methods for the detection of Epstein-Barr virus (EBV)-specific
      antibodies include the immunofluorescence assay (IFA) and enzyme immunoassay
      (EIA). While sensitive and specific, these methods are labor-intensive and
      require separate assays for each analyte. This study evaluated the performance of
      a multiplex bead assay (BioPlex 2200; Bio-Rad Laboratories, Hercules, CA) for the
      simultaneous detection of immunoglobulin G (IgG) and IgM class antibodies to the
      EBV viral capsid antigen (VCA) and IgG class antibodies to Epstein-Barr virus
      nuclear antigen-1 (EBNA-1). Serum specimens (n = 1,315) submitted for routine EBV
      specific antibody testing by EIA (Grifols-Quest, Inc., Miami, FL) were also
      tested by the multiplex bead assay using the BioPlex 2200 automated analyzer.
      Specimens showing discordant results were tested by IFA. Following IFA
      resolution, the BioPlex VCA IgM, VCA IgG, and EBNA-1 IgG assays demonstrated
      97.9%, 91.4%, and 96.9% agreement, respectively, with the results obtained by
      EIA. Furthermore, the BioPlex assays showed an overall agreement of 94.1% with
      the EIA when the specimens were categorized by disease state (susceptible, acute,
      or past infection) based on the EBV-specific antibody profiles. These findings
      indicate that the BioPlex EBV assays demonstrate a performance comparable to that
      of the conventional EIA, while allowing for a more rapid (2.3 h for 100 samples
      versus 4.5 h by the EIA) and higher-throughput ( approximately 400 samples per 9
      h versus 200 samples by the EIA) analysis of the EBV-specific antibody response.

PMID- 18632920
TI  - Oral immunization with recombinant lactobacillus plantarum induces a protective
      immune response in mice with Lyme disease.
AB  - Mucosal immunization is advantageous over other routes of antigen delivery
      because it can induce both mucosal and systemic immune responses. Our goal was to
      develop a mucosal delivery vehicle based on bacteria generally regarded as safe,
      such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as
      a proof of concept. We demonstrate that an oral vaccine based on live recombinant
      Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi
      infection. Our method of expressing vaccine antigens in L. plantarum induces both
      systemic and mucosal immunity after oral administration. This platform technology
      can be applied to design oral vaccine delivery vehicles against several microbial
      pathogens.

PMID- 18632921
TI  - Validation of a competitive enzyme-linked immunosorbent assay for detection of
      Babesia bigemina antibodies in cattle.
AB  - A competitive enzyme-linked immunosorbent assay (cELISA) based on a broadly
      conserved, species-specific, B-cell epitope within the C terminus of Babesia
      bigemina rhoptry-associated protein 1a was validated for international use.
      Receiver operating characteristic analysis revealed 16% inhibition as the
      threshold for a negative result, with an associated specificity of 98.3% and
      sensitivity of 94.7%. Increasing the threshold to 21% increased the specificity
      to 100% but modestly decreased the sensitivity to 87.2%. By using 21% inhibition,
      the positive predictive values ranged from 90.7% (10% prevalence) to 100% (95%
      prevalence) and the negative predictive values ranged from 97.0% (10% prevalence)
      to 48.2% (95% prevalence). The assay was able to detect serum antibody as early
      as 7 days after intravenous inoculation. The cELISA was distributed to five
      different laboratories along with a reference set of 100 defined bovine serum
      samples, including known positive, known negative, and field samples. The
      pairwise concordance among the five laboratories ranged from 100% to 97%, and all
      kappa values were above 0.8, indicating a high degree of reliability. Overall,
      the cELISA appears to have the attributes necessary for international
      application.

PMID- 18632922
TI  - Validation of reference genes in cervical cell samples from human papillomavirus
      infected and -uninfected women for quantitative reverse transcription-PCR assays.
AB  - Reference genes for quantitative reverse transcription-PCR (qRT-PCR) studies must
      be validated for the cell type studied and should be stable between the groups
      that represent the independent variable in an experimental design. We sought to
      identify the reference genes in cervical cell specimens showing the most stable
      expression between human papillomavirus (HPV)-infected and -uninfected women
      without high-grade cervical intraepithelial neoplasia. Using endocervical cells
      collected by cytology brush and Sybr green-based qRT-PCR, eight candidate genes
      were screened for amplification efficiency, specificity, and overall stability
      (by use of geNorm software). The five most stable genes were then further
      evaluated both for overall stability (geNorm) and intergroup stability (by use of
      NormFinder software) in specimens from HPV-negative and HPV-positive women. The
      combination of the glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and
      RPLP0 was the most stable overall, with a geNorm stability measure of 0.603. The
      intergroup analysis showed GAPDH to be the most stable single gene and RPLP0 to
      be second most stable and also showed that these genes represent the most stable
      two-gene combination, with a NormFinder stability value of 0.130. The fact that
      these two distinct approaches identified the same pair of genes provides added
      confidence that, when the focus is on HPV infection, a normalization factor
      derived from these two genes is likely to be appropriate.

PMID- 18632923
TI  - Lipoteichoic acid synergizes with glycosphingolipids to potently stimulate
      secretion of interleukin-6 from human blood cells.
AB  - In the present study, we found that lipoteichoic acid (LTA) synergizes with
      glycosphingolipids to stimulate human blood cells to secrete cytokines. We
      employed globoside, kerasin, and lactosylceramide as representative neutral
      glycosphingolipids and mixed gangliosides GM(2) and GM(3) as representative
      acidic glycosphingolipids. LTA and the glycosphingolipids enhanced cytokine
      secretion by human whole blood, peripheral blood mononuclear cells, and purified
      monocytes in a dose-dependent manner. The level of synergy ranged up to
      approximately 10-fold greater than the additive stimulation caused by LTA and
      glycosphingolipid alone. The greatest synergy was observed with GM(3). We also
      found that LTA synergizes with the synthetic bacterial lipopeptide mimic
      Pam3CysK4. In contrast, the glycosphingolipids suppressed the stimulation caused
      by Pam3CysK4. The stimulation of human cells requires the simultaneous presence
      of LTA and the glycosphingolipids and probably requires their physical
      interactions, as shown by dot blotting and nondenaturing polyacrylamide gel
      electrophoresis experiments. We hypothesize that the enhanced stimulation is due
      to heterooligomers that form between LTA and glycosphingolipids at the
      subcritical micelle concentrations used in these experiments. Previous studies
      showed that LTA also synergizes with hemoglobin. The data taken together suggest
      that LTA may be a pathogen-associated molecular pattern, although its full
      activity requires the presence of a synergistic partner(s).

PMID- 18632924
TI  - Measurement of the humoral immune response following an incident human
      papillomavirus type 16 or 18 infection in young women by a pseudovirion-based
      neutralizing antibody assay.
AB  - We have evaluated a neutralizing antibody assay which uses human papillomavirus
      (HPV) type 16 (HPV-16) and HPV-18 pseudovirions carrying a secretory alkaline
      phosphatase reporter gene and which can potentially measure functionally relevant
      HPV type-specific neutralizing antibodies. The reproducibility of the assay was
      excellent; for HPV-16, the intra- and interassay kappa values were 0.95 and 0.90,
      respectively; and for HPV-18, the corresponding values were 0.90 and 0.90. This
      assay was used to describe the kinetics of the neutralizing antibody response in
      a cohort of 42 young women who were recruited soon after first intercourse and
      who first tested positive for HPV-16 DNA or HPV-18 DNA, or both, during follow
      up. Most women seroconverted following the first detection of type-specific HPV
      DNA and remained seropositive until the end of follow-up. Our findings are
      broadly consistent with those of two other cohort studies which have measured the
      serological response following an incident infection by using the technically
      simpler virus-like-particle-based enzyme-linked immunosorbent assay.

PMID- 18632925
TI  - Diagnosis of central nervous system tuberculosis by T-cell-based assays on
      peripheral blood and cerebrospinal fluid mononuclear cells.
AB  - In active tuberculosis (TB), Mycobacterium tuberculosis-specific T cells are
      compartmentalized more to the site of infection than to the circulating blood.
      Therefore, an M. tuberculosis-specific enzyme-linked immunospot (ELISPOT) assay
      with samples from the site of infection may permit a more sensitive or specific
      diagnosis of active central nervous system (CNS) TB than that achieved by the
      assay with blood alone. Therefore, we prospectively evaluated the usefulness of
      circulating and compartmentalized mononuclear cell (MC; i.e., peripheral blood
      mononuclear cell [PBMC] and cerebrospinal fluid [CSF] MC)-based ELISPOT assays
      (i.e., the T-SPOT.TB test) for the diagnosis of active TB in patients with
      suspected CNS TB. The clinical categories of CNS TB were classified as described
      previously (G. E. Thwaites, T. T. Chau, K. Stepniewska, N. H. Phu, L. V. Chuong,
      D. X. Sinh, N. J. White, C. M. Parry, and J. J. Farrar, Lancet 360:1287-1292,
      2002). Thirty-seven patients with suspected CNS TB were enrolled over a 12-month
      period. Of these, 31 (84%) showed clinical manifestations of suspected TB
      meningitis and 6 (16%) gave indications of intracranial tuberculoma with
      disseminated TB. The final clinical categories of the 37 patients with suspected
      CNS TB were as follows: 12 (32%) were classified as having CNS TB (7 with
      confirmed TB, 3 with probable TB, and 2 with possible TB) and 25 (68%) were
      classified as not having active TB. The sensitivity and specificity of the PBMC
      ELISPOT assay were 91% (95% confidence interval [CI], 59% to 100%) and 63% (95%
      CI, 41% to 81%), respectively. By comparison, the sensitivity and specificity of
      the CSF MC ELISPOT assay were 75% (95% CI, 19% to 99%) and 75% (95% CI, 43% to
      95%), respectively. When the ratio of the CSF MC ELISPOT assay results to the
      PBMC ELISPOT results was 2 or more, the sensitivity and specificity were 50% (95%
      CI, 7% to 93%) and 100% (95% CI, 74% to 100%), respectively. The ELISPOT assay
      with PBMCs and CSF MCs is a useful adjunct to the current tests for the diagnosis
      of CNS TB.

PMID- 18632926
TI  - Rapid immunochromatographic strip test for detection of anti-K39 immunoglobulin G
      antibodies for diagnosis of visceral leishmaniasis.
AB  - InBios International has developed an immunochromatographic rapid strip for the
      detection of visceral leishmaniasis that requires minimal equipment and only a
      small amount of blood to run a test. We compared the InBios rapid strip test with
      the CDC immunofluorescent antibody assay, and the agreement, sensitivity, and
      specificity were 98%, 90%, and 100%, respectively.

PMID- 18632927
TI  - Bidirectional changes in the intrinsic excitability of infralimbic neurons
      reflect a possible regulatory role in the acquisition and extinction of Pavlovian
      conditioned fear.

PMID- 18632928
TI  - Corpus callosum and bimanual coordination in multiple sclerosis.

PMID- 18632929
TI  - Distinct roles for two histamine receptors (hclA and hclB) at the Drosophila
      photoreceptor synapse.
AB  - Histamine (HA) is the photoreceptor neurotransmitter in arthropods, directly
      gating chloride channels on large monopolar cells (LMCs), postsynaptic to
      photoreceptors in the lamina. Two histamine-gated channel genes that could
      contribute to this channel in Drosophila are hclA (also known as ort) and hclB
      (also known as hisCl1), both encoding novel members of the Cys-loop receptor
      superfamily. Drosophila S2 cells transfected with these genes expressed both
      homomeric and heteromeric histamine-gated chloride channels. The
      electrophysiological properties of these channels were compared with those from
      isolated Drosophila LMCs. HCLA homomers had nearly identical HA sensitivity to
      the native receptors (EC(50) = 25 microM). Single-channel analysis revealed
      further close similarity in terms of single-channel kinetics and subconductance
      states ( approximately 25, 40, and 60 pS, the latter strongly voltage dependent).
      In contrast, HCLB homomers and heteromeric receptors were more sensitive to HA
      (EC(50) = 14 and 1.2 microM, respectively), with much smaller single-channel
      conductances ( approximately 4 pS). Null mutations of hclA (ort(US6096))
      abolished the synaptic transients in the electroretinograms (ERGs). Surprisingly,
      the ERG "on" transients in hclB mutants transients were approximately twofold
      enhanced, whereas intracellular recordings from their LMCs revealed altered
      responses with slower kinetics. However, HCLB expression within the lamina,
      assessed by both a GFP (green fluorescent protein) reporter gene strategy and
      mRNA tagging, was exclusively localized to the glia cells, whereas HCLA
      expression was confirmed in the LMCs. Our results suggest that the native
      receptor at the LMC synapse is an HCLA homomer, whereas HCLB signaling via the
      lamina glia plays a previously unrecognized role in shaping the LMC postsynaptic
      response.

PMID- 18632930
TI  - Cortical action potential backpropagation explains spike threshold variability
      and rapid-onset kinetics.
AB  - Neocortical action potential responses in vivo are characterized by considerable
      threshold variability, and thus timing and rate variability, even under seemingly
      identical conditions. This finding suggests that cortical ensembles are required
      for accurate sensorimotor integration and processing. Intracellularly, trial-to
      trial variability results not only from variation in synaptic activities, but
      also in the transformation of these into patterns of action potentials. Through
      simultaneous axonal and somatic recordings and computational simulations, we
      demonstrate that the initiation of action potentials in the axon initial segment
      followed by backpropagation of these spikes throughout the neuron results in a
      distortion of the relationship between the timing of synaptic and action
      potential events. In addition, this backpropagation also results in an unusually
      high rate of rise of membrane potential at the foot of the action potential. The
      distortion of the relationship between the amplitude time course of synaptic
      inputs and action potential output caused by spike backpropagation results in the
      appearance of high spike threshold variability at the level of the soma. At the
      point of spike initiation, the axon initial segment, threshold variability is
      considerably less. Our results indicate that spike generation in cortical neurons
      is largely as expected by Hodgkin-Huxley theory and is more precise than
      previously thought.

PMID- 18632931
TI  - Self-limited hyperexcitability: functional effect of a familial hemiplegic
      migraine mutation of the Nav1.1 (SCN1A) Na+ channel.
AB  - Familial hemiplegic migraine (FHM) is an autosomal dominant inherited subtype of
      severe migraine with aura. Mutations causing FHM (type 3) have been identified in
      SCN1A, the gene encoding neuronal voltage-gated Na(v)1.1 Na(+) channel alpha
      subunit, but functional studies have been done using the cardiac Na(v)1.5
      isoform, and the observed effects were similar to those of some epileptogenic
      mutations. We studied the FHM mutation Q1489K by transfecting tsA-201 cells and
      cultured neurons with human Na(v)1.1. We show that the mutation has effects on
      the gating properties of the channel that can be consistent with both
      hyperexcitability and hypoexcitability. Simulation of neuronal firing and long
      depolarizing pulses mimicking promigraine conditions revealed that the effect of
      the mutation is a gain of function consistent with increased neuronal firing.
      However, during high-frequency discharges and long depolarizations, the effect
      became a loss of function. Recordings of firing of transfected neurons showed
      higher firing frequency at the beginning of long discharges. This self-limited
      capacity to induce neuronal hyperexcitability may be a specific characteristic of
      migraine mutations, able to both trigger the cascade of events that leads to
      migraine and counteract the development of extreme hyperexcitability typical of
      epileptic seizures. Thus, we found a possible difference in the functional
      effects of FHM and familial epilepsy mutations of Nav1.1.

PMID- 18632932
TI  - Chronic psychoemotional stress impairs cannabinoid-receptor-mediated control of
      GABA transmission in the striatum.
AB  - Exposure to stressful events has a myriad of consequences in animals and in
      humans, and triggers synaptic adaptations in many brain areas. Stress might also
      alter cannabinoid-receptor-mediated transmission in the brain, but no
      physiological study has addressed this issue so far. In the present study, we
      found that social defeat stress, induced in mice by exposure to aggression,
      altered cannabinoid CB(1)-receptor-mediated control of synaptic transmission in
      the striatum. In fact, the presynaptic inhibition of GABAergic IPSCs induced by
      the cannabinoid CB(1) receptor agonist HU210 [(6aR)-trans-3-(1,1-dimethylheptyl)
      6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol]
      was reduced after a single stressful episode and fully abolished after 3 and 7 d
      of stress exposure. Repeated psychoemotional stress also impaired the sensitivity
      of GABA synapses to endocannabinoids mobilized by group I metabotropic glutamate
      receptor stimulation, whereas the cannabinoid CB(1)-mediated control of glutamate
      transmission was unaffected by repeated exposure to an aggressor. Corticosteroids
      released in response to the activation of the hypothalamic-pituitary-adrenal axis
      played a major role in the synaptic defects observed in stressed animals, because
      these alterations were fully prevented by pharmacological blockade of
      glucocorticoid receptors and were mimicked by corticosterone injections. The
      recovery of stress-induced synaptic defects was favored when stressed mice were
      given access to a running wheel or to sucrose consumption, which function as
      potent natural rewards. A similar rescuing effect was obtained by a single
      injection of cocaine, a psychostimulant with strong rewarding properties.
      Targeting cannabinoid CB(1) receptors or endocannabinoid metabolism might be a
      valuable option to treat stress-associated neuropsychiatric conditions.

PMID- 18632934
TI  - Interactions between medial temporal lobe, prefrontal cortex, and inferior
      temporal regions during visual working memory: a combined intracranial EEG and
      functional magnetic resonance imaging study.
AB  - It is a fundamental question whether the medial temporal lobe (MTL) supports only
      long-term memory encoding, or contributes to working memory (WM) processes as
      well. Recent data suggest that the MTL is activated whenever multiple items or
      item features are being maintained in WM. This may rely on interactions between
      the MTL or the prefrontal cortex (PFC) and content-specific areas in the inferior
      temporal (IT) cortex. Here, we investigated the neural mechanism through which
      the MTL, PFC, and IT cortex interact during WM maintenance. First, we quantified
      phase synchronization of intracranial EEG data in epilepsy patients with
      electrodes in both regions. Second, we used directional coupling analysis to
      study whether oscillatory activity in the IT cortex drives the MTL or vice versa.
      Finally, we investigated functional connectivity in functional magnetic resonance
      imaging data of healthy subjects with seeds in the MTL and PFC. With increasing
      load, EEG phase synchronization between the IT cortex and anterior
      parahippocampal gyrus and within the MTL increased. Coupling was bidirectional in
      all load conditions, but changed toward an increased top-down (anterior
      parahippocampal gyrus --> IT) coupling in the high gamma range (51-75 Hz) with
      increasing load. Functional connectivity between the MTL seed and the visual
      association cortex increased with load, but activity within the MTL and the PFC
      correlated with fewer voxels, suggesting that more specific neural networks were
      engaged. These data indicate that WM for multiple items depends on an increased
      strength of top-down control of activity within the IT cortex by the MTL.

PMID- 18632933
TI  - Small-molecule protein tyrosine phosphatase inhibition as a neuroprotective
      treatment after spinal cord injury in adult rats.
AB  - Spinal cord injury causes progressive secondary tissue degeneration, leaving many
      injured people with neurological disabilities. There are no satisfactory
      neuroprotective treatments. Protein tyrosine phosphatases inactivate neurotrophic
      factor receptors and downstream intracellular signaling molecules. Thus, we
      tested whether the peroxovanadium compound potassium bisperoxo(1,10
      phenanthroline)oxovanadate (V) [bpV(phen)], a stable, potent and selective
      protein tyrosine phosphatase inhibitor, would be neuroprotective after a thoracic
      spinal cord contusion in adult rats. Intrathecal bpV(phen) infusions through a
      lumbar puncture rescued dorsal column sensory axons innervating the nucleus
      gracilis and white matter at the injury epicenter. At the most effective dose,
      essentially all of these axons and most of the white matter at the epicenter were
      spared (vs approximately 60% with control infusions). bpV(phen) treatments
      started 4 h after contusion were fully effective. This treatment greatly improved
      and normalized sensorimotor function in a grid-walking test and provided complete
      axonal protection over 6 weeks. The treatment rescued sensory-evoked potentials
      that disappeared after dorsal column transection. bpV(phen) affected early
      degenerative mechanisms, because the main effects were seen at 7 d and lasted
      beyond the treatment period. The neuroprotection appeared to be mediated by
      rescue of blood vessels. bpV(phen) reduced apoptosis of cultured endothelial
      cells. These results show that a small molecule, used in a clinically relevant
      manner, reduces loss of long-projecting axons, myelin, blood vessels, and
      function in a model relevant to the most common type of spinal cord injury in
      humans. They reveal a novel mechanism of spinal cord degeneration involving
      protein tyrosine phosphatases that can be targeted with therapeutic drugs.

PMID- 18632935
TI  - Salicylate enables cochlear arachidonic-acid-sensitive NMDA receptor responses.
AB  - Currently, many millions of people treated for various ailments receive high
      doses of salicylate. Consequently, understanding the mechanisms by which
      salicylate induces tinnitus is an important issue for the research community.
      Behavioral testing in rats have shown that tinnitus induced by salicylate or
      mefenamate (both cyclooxygenase blockers) are mediated by cochlear NMDA
      receptors. Here we report that the synapses between the sensory inner hair cells
      and the dendrites of the cochlear spiral ganglion neurons express NMDA receptors.
      Patch-clamp recordings and two-photon calcium imaging demonstrated that
      salicylate and arachidonate (a substrate of cyclooxygenase) enabled the calcium
      flux and the neural excitatory effects of NMDA on cochlear spiral ganglion
      neurons. Salicylate also increased the arachidonate content of the whole cochlea
      in vivo. Single-unit recordings of auditory nerve fibers in adult guinea pig
      confirmed the neural excitatory effect of salicylate and the blockade of this
      effect by NMDA antagonist. These results suggest that salicylate inhibits
      cochlear cyclooxygenase, which increased levels of arachidonate. The increased
      levels of arachidonate then act on NMDA receptors to enable NMDA responses to
      glutamate that inner hair cells spontaneously release. This new pharmacological
      profile of salicylate provides a molecular mechanism for the generation of
      tinnitus at the periphery of the auditory system.

PMID- 18632936
TI  - Different CA1 and CA3 representations of novel routes in a shortcut situation.
AB  - Place cells are hippocampal neurons whose discharge is strongly related to a
      rat's location in its environment. The existence of place cells has led to the
      proposal that they are part of an integrated neural system dedicated to spatial
      navigation. To further understand the relationships between place cell firing and
      spatial problem solving, we examined the discharge of CA1 and CA3 place cells as
      rats were exposed to a shortcut in a runway maze. On specific sessions, a wall
      section of the maze was removed so as to open a shorter novel route within the
      otherwise familiar maze. We found that the discharge of both CA1 and CA3 cells
      was strongly affected in the vicinity of the shortcut region but was much less
      affected farther away. In addition, CA3 fields away from the shortcut were more
      altered than CA1 fields. Thus, place cell firing appears to reflect more than
      just the animal's spatial location and may provide additional information about
      possible motions, or routes, within the environment. This kinematic
      representation appears to be spatially more extended in CA3 than in CA1,
      suggesting interesting computational differences between the two subregions.

PMID- 18632937
TI  - Effect of stimulus intensity on the spike-local field potential relationship in
      the secondary somatosensory cortex.
AB  - Neuronal oscillations in the gamma frequency range have been reported in many
      cortical areas, but the role they play in cortical processing remains unclear. We
      tested a recently proposed hypothesis that the intensity of sensory input is
      coded in the timing of action potentials relative to the phase of gamma
      oscillations, thus converting amplitude information to a temporal code. We
      recorded spikes and local field potential (LFP) from secondary somatosensory
      (SII) cortex in awake monkeys while presenting a vibratory stimulus at different
      amplitudes. We developed a novel technique based on matching pursuit to study the
      interaction between the highly transient gamma oscillations and spikes with high
      time-frequency resolution. We found that spikes were weakly coupled to LFP
      oscillations in the gamma frequency range (40-80 Hz), and strongly coupled to
      oscillations in higher gamma frequencies. However, the phase relationship of
      neither low-gamma nor high-gamma oscillations changed with stimulus intensity,
      even with a 10-fold increase. We conclude that, in SII, gamma oscillations are
      synchronized with spikes, but their phase does not vary with stimulus intensity.
      Furthermore, high-gamma oscillations (>60 Hz) appear to be closely linked to the
      occurrence of action potentials, suggesting that LFP high-gamma power could be a
      sensitive index of the population firing rate near the microelectrode.

PMID- 18632938
TI  - Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic
      amphetamine exposure.
AB  - The molecular mechanisms underlying the transition from recreational drug use to
      chronic addiction remain poorly understood. One molecule implicated in this
      process is DeltaFosB, a transcription factor that accumulates in striatum after
      repeated drug exposure and mediates sensitized behavioral responses to
      psychostimulants and other drugs of abuse. The downstream transcriptional
      mechanisms by which DeltaFosB regulates drug-induced behaviors are incompletely
      understood. We reported previously the chromatin remodeling mechanisms by which
      DeltaFosB activates the expression of certain genes; however, the mechanisms
      underlying DeltaFosB-mediated gene repression remain unknown. Here, we identify c
      fos, an immediate early gene rapidly induced in striatum after acute
      psychostimulant exposure, as a novel downstream target that is repressed
      chronically by DeltaFosB. We show that accumulation of DeltaFosB in striatum
      after chronic amphetamine treatment desensitizes c-fos mRNA induction to a
      subsequent drug dose. DeltaFosB desensitizes c-fos expression by recruiting
      histone deacetylase 1 (HDAC1) to the c-fos gene promoter, which, in turn,
      deacetylates surrounding histones and attenuates gene activity. Accordingly,
      local knock-out of HDAC1 in striatum abolishes amphetamine-induced
      desensitization of the c-fos gene. In concert, chronic amphetamine increases
      histone H3 methylation on the c-fos promoter, a chromatin modification also known
      to repress gene activity, as well as expression levels of the H3 histone
      methyltransferase, KMT1A (lysine methyltransferase 1A, formerly SUV39H1). This
      study reveals a novel epigenetic pathway through which DeltaFosB mediates
      distinct transcriptional programs that may ultimately alter behavioral plasticity
      to chronic amphetamine exposure.

PMID- 18632939
TI  - Hedgehog signaling regulates sensory cell formation and auditory function in mice
      and humans.
AB  - Auditory perception is mediated through a finite number of mechanosensory hair
      cells located in a specialized sensory epithelium within the inner ear. The
      formation of the appropriate number of hair cells and the location of those cells
      is crucial for normal auditory function. However, the factors that regulate the
      formation of this epithelium remain poorly understood. Truncating mutations in
      the transcription factor GLI3, a downstream effector of the Hedgehog (HH)
      pathway, lead to a partial loss of HH signaling and cause Pallister-Hall syndrome
      (PHS). Here, we report that cochleae from a mouse model of PHS (Gli3(Delta699)),
      which produces only the truncated, repressor form of GLI3, have a variably
      penetrant phenotype that includes an increase in the size of the sensory
      epithelium and the development of large ectopic sensory patches in Kolliker's
      organ (KO). Consistent with the mouse model, some PHS individuals exhibit hearing
      loss across a broad range of frequencies. Moreover, inhibition of HH signaling in
      vitro results in an increase in the size of the prosensory domain, a precursor
      population that gives rise to the sensory epithelium, whereas treatment with
      Sonic hedgehog (SHH) inhibits prosensory formation. Finally, we demonstrate that
      HH signaling within the cochlea regulates expression of prosensory markers and
      that the effects of HH in KO are dependent on activation of Notch, an inducer of
      prosensory fate. These results suggest that HH signaling plays a key role in the
      specification, size, and location of the prosensory domain, and therefore of hair
      cells, within the cochlea.

PMID- 18632940
TI  - Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.
AB  - Previous studies have demonstrated the presence of functional glycine receptors
      (GlyRs) in hippocampus. In this work, we examine the baseline activity and
      activity-dependent modulation of GlyRs in region CA1. We find that strychnine
      sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of
      tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical
      stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting
      conductance is independent of the presynaptic stimulation rate; however, pairs of
      presynaptic and postsynaptic action potentials, repeated at frequencies above 5
      Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to
      levels at least 20% larger than those seen with presynaptic stimulation alone. We
      refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR
      agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic
      GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all
      conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine
      application, suggesting that a reduction in the number or sensitivity of membrane
      inserted GlyRs underlies RDE. By extending the RDE induction protocol to include
      500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic
      depression (LTD). Manipulations that lead to reduced functionality of GlyRs,
      either pharmacologically or through RDE, also lead to increased LTD. This result
      suggests that RDE contributes to long-term synaptic plasticity in the
      hippocampus.

PMID- 18632941
TI  - Step training reinforces specific spinal locomotor circuitry in adult spinal
      rats.
AB  - Locomotor training improves function after a spinal cord injury both in
      experimental and clinical settings. The activity-dependent mechanisms underlying
      such improvement, however, are sparsely understood. Adult rats received a
      complete spinal cord transection (T9), and epidural stimulation (ES) electrodes
      were secured to the dura matter at L2. EMG electrodes were implanted bilaterally
      in selected muscles. Using a servo-controlled body weight support system for
      bipedal stepping, five rats were trained 7 d/week for 6 weeks (30 min/d) under
      quipazine (0.3 mg/kg) and ES (L2; 40 Hz). Nontrained rats were handled as trained
      rats but did not receive quipazine or ES. At the end of the experiment, a subset
      of rats was used for c-fos immunohistochemistry. Three trained and three
      nontrained rats stepped for 1 h (ES; no quipazine) and were returned to their
      cages for 1 h before intracardiac perfusion. All rats could step with ES and
      quipazine administration. The trained rats had higher and longer steps, narrower
      base of support at stance, and lower variability in EMG parameters than
      nontrained rats, and these properties approached that of noninjured controls.
      After 1 h of stepping, the number of FOS+ neurons was significantly lower in
      trained than nontrained rats throughout the extent of the lumbosacral segments.
      These results suggest that training reinforces the efficacy of specific
      sensorimotor pathways, resulting in a more selective and stable network of
      neurons that controls locomotion.

PMID- 18632942
TI  - Functional topography and integration of the contralateral and ipsilateral
      retinocollicular projections of ephrin-A-/- mice.
AB  - Topographically ordered projections are established by molecular guidance cues
      and refined by neuronal activity. Retinal input to a primary visual center, the
      superior colliculus (SC), is bilateral with a dense contralateral projection and
      a sparse ipsilateral one. Both projections are topographically organized, but in
      opposing anterior-posterior orientations. This arrangement provides functionally
      coherent input to each colliculus from the binocular visual field, supporting
      visual function. When guidance cues involved in contralateral topography (ephrin
      As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate
      terminations within the SC. However, the organization of the ipsilateral
      projection relative to the abnormal contralateral input remains unknown, as does
      the functional capacity of both projections. We show here that in ephrin-A(-/-)
      mice, the SC contains an expanded, diffuse ipsilateral projection.
      Electrophysiological recording demonstrated that topography of visually evoked
      responses recorded from the contralateral superior colliculus of ephrin-A(-/-)
      mice displayed similar functional disorder in all genotypes, contrasting with
      their different degrees of anatomical disorder. In contrast, ipsilateral
      responses were retinotopic in ephrin-A2(-/-) but disorganized in ephrin-A2/A5(-/
      ) mice. The lack of integration of binocular input resulted in specific visual
      deficits, which could be reversed by occlusion of one eye. The discrepancy
      between anatomical and functional topography in both the ipsilateral and
      contralateral projections implies suppression of inappropriately located
      terminals. Moreover, the misalignment of ipsilateral and contralateral visual
      information in ephrin-A2/A5(-/-) mice suggests a role for ephrin-As in
      integrating convergent visual inputs.

PMID- 18632943
TI  - SCLIP is crucial for the formation and development of the Purkinje cell dendritic
      arbor.
AB  - Cerebellar Purkinje cells elaborate one of the most complex dendritic arbors
      among neurons to integrate the numerous signals they receive from the cerebellum
      circuitry. Their dendritic differentiation undergoes successive, tightly
      regulated phases of development involving both regressive and growth events.
      Although many players regulating the late phases of Purkinje cell dendritogenesis
      have been identified, intracellular factors controlling earlier phases of
      dendritic development remain mostly unknown. In this study, we explored the
      biological properties and functions of SCLIP, a protein of the stathmin family,
      in Purkinje cell dendritic differentiation and cerebellum development. Unlike the
      other stathmins, SCLIP is strongly expressed in Purkinje cells during cerebellar
      development and accumulates in their dendritic processes at a critical period of
      their formation and outgrowth. To reveal SCLIP functions, we developed a
      lentiviral-mediated approach on cerebellar organotypic cultures to inhibit or
      increase its expression in Purkinje cells in their tissue environment. Depletion
      of SCLIP promoted retraction of the Purkinje cell primitive process and then
      prevented the formation of new dendrites at early stages of postnatal
      development. It also prevented their elongation and branching at later phases of
      differentiation. Conversely, SCLIP overexpression promoted dendritic branching
      and development. Together, our results demonstrate for the first time that SCLIP
      is crucial for both the formation and proper development of Purkinje cell
      dendritic arbors. SCLIP appears thus as a novel and specific factor that controls
      the early phases of Purkinje cell dendritic differentiation during cerebellum
      development.

PMID- 18632944
TI  - Fluorescence changes of genetic calcium indicators and OGB-1 correlated with
      neural activity and calcium in vivo and in vitro.
AB  - Recent advance in the design of genetically encoded calcium indicators (GECIs)
      has further increased their potential for direct measurements of activity in
      intact neural circuits. However, a quantitative analysis of their fluorescence
      changes (DeltaF) in vivo and the relationship to the underlying neural activity
      and changes in intracellular calcium concentration (Delta[Ca(2+)](i)) has not
      been given. We used two-photon microscopy, microinjection of synthetic Ca(2+)
      dyes and in vivo calibration of Oregon-Green-BAPTA-1 (OGB-1) to estimate
      [Ca(2+)](i) at rest and Delta[Ca(2+)](i) at different action potential
      frequencies in presynaptic motoneuron boutons of transgenic Drosophila larvae. We
      calibrated DeltaF of eight different GECIs in vivo to neural activity,
      Delta[Ca(2+)](i), and DeltaF of purified GECI protein at similar Delta[Ca(2+)] in
      vitro. Yellow Cameleon 3.60 (YC3.60), YC2.60, D3cpv, and TN-XL exhibited twofold
      higher maximum DeltaF compared with YC3.3 and TN-L15 in vivo. Maximum DeltaF of
      GCaMP2 and GCaMP1.6 were almost identical. Small Delta[Ca(2+)](i) were reported
      best by YC3.60, D3cpv, and YC2.60. The kinetics of Delta[Ca(2+)](i) was massively
      distorted by all GECIs, with YC2.60 showing the slowest kinetics, whereas TN-XL
      exhibited the fastest decay. Single spikes were only reported by OGB-1; all GECIs
      were blind for Delta[Ca(2+)](i) associated with single action potentials. YC3.60
      and D3cpv tentatively reported spike doublets. In vivo, the K(D) (dissociation
      constant) of all GECIs was shifted toward lower values, the Hill coefficient was
      changed, and the maximum DeltaF was reduced. The latter could be attributed to
      resting [Ca(2+)](i) and the optical filters of the equipment. These results
      suggest increased sensitivity of new GECIs but still slow on rates for calcium
      binding.

PMID- 18632945
TI  - The time course of transmitter at glycinergic synapses onto motoneurons.
AB  - The concentration of transmitter in the synaptic cleft and its clearance time are
      one of the main determinants of synaptic strength. We estimated the time course
      of glycine at rat lumbar motoneurons synapses in spinal cord slices by recording
      synaptic currents in the presence of a low-affinity competitive antagonist at
      glycine receptors [2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium
      (SR-95531)]. Data were analyzed by using the established activation mechanism for
      glycine receptors and our measurements of SR-95531 binding rates. We show that
      this technique alone is not sufficient to determine simultaneously the peak
      concentration of transmitter and its clearance time. However, we found that block
      of the glial glycine transporter prolongs the glycine transient. This observation
      puts additional constraints on the range of possible values of the time course of
      glycine, indicating that glycine reaches a peak concentration of 2.2-3.5 mM and
      is cleared from the cleft with a time constant of 0.6-0.9 ms.

PMID- 18632946
TI  - Pyramidal tract stimulation restores normal corticospinal tract connections and
      visuomotor skill after early postnatal motor cortex activity blockade.
AB  - Motor development depends on forming specific connections between the
      corticospinal tract (CST) and the spinal cord. Blocking CST activity in kittens
      during the critical period for establishing connections with spinal motor
      circuits results in permanent impairments in connectivity and function. The
      changes in connections are consistent with the hypothesis that the inactive tract
      is less competitive in developing spinal connections than the active tract. In
      this study, we tested the competition hypothesis by determining whether
      activating CST axons, after previous silencing during the critical period,
      abrogated development of aberrant corticospinal connections and motor
      impairments. In kittens, we inactivated motor cortex by muscimol infusion between
      postnatal weeks 5 and 7. Next, we electrically stimulated CST axons in the
      medullary pyramid 2.5 h daily, between weeks 7 and 10. In controls (n = 3), CST
      terminations were densest within the contralateral deeper, premotor, spinal
      layers. After previous inactivation (n = 3), CST terminations were densest within
      the dorsal, somatic sensory, layers. There were more ipsilateral terminations
      from the active tract. During visually guided locomotion, there was a movement
      endpoint impairment. Stimulation after inactivation (n = 6) resulted in
      significantly fewer terminations in the sensory layers and more in the premotor
      layers, and fewer ipsilateral connections from active cortex. Chronic stimulation
      reduced the current threshold for evoking contralateral movements by pyramidal
      stimulation, suggesting strengthening of connections. Importantly, stimulation
      significantly improved stepping accuracy. These findings show the importance of
      activity-dependent processes in specifying CST connections. They also provide a
      strategy for harnessing activity to rescue CST axons at risk of developing
      aberrant connections after CNS injury.

PMID- 18632947
TI  - Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte
      maturation and myelin formation.
AB  - Nogo-A is one of the most potent oligodendrocyte-derived inhibitors for axonal
      regrowth in the injured adult CNS. However, the physiological function of Nogo-A
      in development and in healthy oligodendrocytes is still unknown. In the present
      study, we investigated the role of Nogo-A for myelin formation in the developing
      optic nerve. By quantitative real-time PCR, we found that the expression of Nogo
      A increased faster in differentiating oligodendrocytes than that of the major
      myelin proteins MBP (myelin basic protein), PLP (proteolipid protein)/DM20, and
      CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase). The analysis of optic nerves
      and cerebella of mice deficient for Nogo-A (Nogo-A(-/-)) revealed a marked delay
      of oligodendrocyte differentiation, myelin sheath formation, and axonal caliber
      growth within the first postnatal month. The combined deletion of Nogo-A and MAG
      caused a more severe transient hypomyelination. In contrast to MAG(-/-) mice,
      Nogo-A(-/-) mutants did not present abnormalities in the structure of myelin
      sheaths and Ranvier nodes. The common binding protein for Nogo-A and MAG, NgR1,
      was exclusively upregulated in MAG(-/-) animals, whereas the level of Lingo-1, a
      coreceptor, remained unchanged. Together, our results demonstrate that Nogo-A and
      MAG are differently involved in oligodendrocyte maturation in vivo, and suggest
      that Nogo-A may influence also remyelination in pathological conditions such as
      multiple sclerosis.

PMID- 18632948
TI  - Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior
      cingulate cortex.
AB  - Neuropathic pain is caused by a primary lesion or dysfunction in the nervous
      system. Investigations have mainly focused on the spinal mechanisms of
      neuropathic pain, and less is known about cortical changes in neuropathic pain.
      Here, we report that peripheral nerve injury triggered long-term changes in
      excitatory synaptic transmission in layer II/III neurons within the anterior
      cingulate cortex (ACC). Both the presynaptic release probability of glutamate and
      postsynaptic glutamate AMPA receptor-mediated responses were enhanced after
      injury using the mouse peripheral nerve injury model. Western blot showed
      upregulated phosphorylation of GluR1 in the ACC after nerve injury. Finally, we
      found that both presynaptic and postsynaptic changes after nerve injury were
      absent in genetic mice lacking calcium-stimulated adenylyl cyclase 1 (AC1). Our
      studies therefore provide direct integrative evidence for both long-term
      presynaptic and postsynaptic changes in cortical synapses after nerve injury, and
      that AC1 is critical for such long-term changes. AC1 thus may serve as a
      potential therapeutic target for treating neuropathic pain.

PMID- 18632950
TI  - Positive selection at the receptor-binding site of haemagglutinin H5 in viral
      sequences derived from human tissues.
AB  - Highly pathogenic H5N1 avian influenza virus has spread through at least 45
      countries in three continents. Despite the ability to infect and cause severe
      disease in humans, the virus cannot transmit efficiently from human to human. The
      lack of efficient transmission indicates the incompletion of the adaptation of
      the avian virus to the new host species. The required mutations for the complete
      adaptation and the emergence of a potential pandemic virus are likely to
      originate and be selected within infected human tissues. Differential receptor
      preference plays an important role in the species-tropism of avian influenza. We
      have analysed quasispecies of sequences covering the receptor-binding domain of
      the haemagglutinin gene of H5N1 viruses derived from fatal human cases. We
      employed a likelihood ratio test to identify positive-selection sites within the
      quasispecies. Nine of seventeen positive-selection sites identified in our
      analyses were found to be located within or flanking the receptor-binding domain.
      Some of these mutations are known to alter receptor-binding specificity. This
      suggests that our approach could be used to screen for mutations with significant
      functional impact. Our data provide new candidate mutations for the viral
      adaptation to a human host, and a new approach to search for new genetic markers
      of potential pandemic viruses.

PMID- 18632951
TI  - Tomato spotted wilt virus glycoproteins induce the formation of endoplasmic
      reticulum- and Golgi-derived pleomorphic membrane structures in plant cells.
AB  - Tomato spotted wilt virus (TSWV) particles are spherical and enveloped, an
      uncommon feature among plant infecting viruses. Previous studies have shown that
      virus particle formation involves the enwrapment of ribonucleoproteins with viral
      glycoprotein containing Golgi stacks. In this study, the localization and
      behaviour of the viral glycoproteins Gn and Gc were analysed, upon transient
      expression in plant protoplasts. When separately expressed, Gc was solely
      observed in the endoplasmic reticulum (ER), whereas Gn was found both within the
      ER and Golgi membranes. Upon co-expression, both glycoproteins were found at ER
      export sites and ultimately at the Golgi complex, confirming the ability of Gn to
      rescue Gc from the ER, possibly due to heterodimerization. Interestingly, both Gc
      and Gn were shown to induce the deformation of ER and Golgi membranes,
      respectively, also observed upon co-expression of the two glycoproteins. The
      behaviour of both glycoproteins within the plant cell and the phenomenon of
      membrane deformation are discussed in light of the natural process of viral
      infection.

PMID- 18632949
TI  - Bluetongue virus: dissection of the polymerase complex.
AB  - Bluetongue is a vector-borne viral disease of ruminants that is endemic in
      tropical and subtropical countries. Since 1998 the virus has also appeared in
      Europe. Partly due to the seriousness of the disease, bluetongue virus (BTV), a
      member of genus Orbivirus within the family Reoviridae, has been a subject of
      intense molecular study for the last three decades and is now one of the best
      understood viruses at the molecular and structural levels. BTV is a complex non
      enveloped virus with seven structural proteins arranged in two capsids and a
      genome of ten double-stranded (ds) RNA segments. Shortly after cell entry, the
      outer capsid is lost to release an inner capsid (the core) which synthesizes
      capped mRNAs from each genomic segment, extruding them into the cytoplasm. This
      requires the efficient co-ordination of a number of enzymes, including helicase,
      polymerase and RNA capping activities. This review will focus on our current
      understanding of these catalytic proteins as derived from the use of recombinant
      proteins, combined with functional assays and the in vitro reconstitution of the
      transcription/replication complex. In some cases, 3D structures have complemented
      this analysis to reveal the fine structural detail of these proteins. The
      combined activities of the core enzymes produce infectious transcripts necessary
      and sufficient to initiate BTV infection. Such infectious transcripts can now be
      synthesized wholly in vitro and, when introduced into cells by transfection, lead
      to the recovery of infectious virus. Future studies thus hold the possibility of
      analysing the consequence of mutation in a replicating virus system.

PMID- 18632952
TI  - Initiation of hepatitis B virus genome replication and production of infectious
      virus following delivery in HepG2 cells by novel recombinant baculovirus vector.
AB  - One of the major problems in gaining further insight into hepatitis B virus
      (HBV)/host-cell interactions is to improve the existing cellular models for the
      study of HBV replication. The first objective of this study was to improve the
      system based on transduction of HepG2 cells with a recombinant baculovirus to
      study HBV replication. A new HBV recombinant baculovirus, Bac-HBV-1.1, in which
      the synthesis of pre-genomic RNA is driven by a strong mammalian promoter, was
      generated. Transduction with this new recombinant baculovirus led to higher
      levels of HBV replication in HepG2 cells compared with levels obtained with
      previously described baculovirus vectors. The initiation of a complete HBV DNA
      replication cycle in Bac-HBV-1.1-transduced HepG2 cells was shown by the presence
      of HBV replicative intermediates, including covalently closed circular DNA
      (cccDNA). Only low levels of cccDNA were detected in the nucleus of infected
      cells. Data showed that cccDNA resulted from the recycling of newly synthesized
      nucleocapsids and was bound to acetylated histones in a chromatin-like structure.
      HBV particles released into the supernatant of transduced HepG2 cells were
      infectious in differentiated HepaRG cells. Several Bac-HBV-1.1 baculoviruses
      containing HBV strains carrying mutations conferring resistance to lamivudine
      and/or adefovir were constructed. Phenotypic analysis of these mutants confirmed
      the results obtained with the transfection procedures. In conclusion, an improved
      cell-culture system was established for the transduction of replication-competent
      HBV genomes. This will be useful for future studies of the fitness of HBV
      mutants.

PMID- 18632953
TI  - D2: major subgenotype of hepatitis B virus in Russia and the Baltic region.
AB  - Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13
      genotype A and 42 genotype D strains from the former USSR. The strains were
      classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced
      gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype
      specific residues, and a region spanning residues 58-128 in the spacer region of
      the P gene could be used to distinguish between D1 and D4. This enabled the
      allocation to subgenotype of strains with partially sequenced genomes. D2 was
      dominating, while D3 was found in low frequency in the whole region. D1 was most
      prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences
      between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively.
      The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and
      D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2
      strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes
      were closely related at the level of complete genomes and formed geographically
      specific clades with low intraclade divergences, possibly indicating past
      iatrogenic spread. It is not clear whether the finding of four subgenotypes in
      the area corresponds to separate introductions of the virus or to previous
      population migrations into the area. An earlier introduction of D3 compared with
      D2 was supported by its higher intra-subgenotype divergence, while the lower
      divergence within D1 is probably due to a more recent emergence.

PMID- 18632954
TI  - Identification of novel porcine and bovine parvoviruses closely related to human
      parvovirus 4.
AB  - Human parvovirus 4 (PARV4), a recently discovered parvovirus found exclusively in
      human plasma and liver tissue, was considered phylogenetically distinct from
      other parvoviruses. Here, we report the discovery of two novel parvoviruses
      closely related to PARV4, porcine hokovirus (PHoV) and bovine hokovirus (BHoV),
      from porcine and bovine samples in Hong Kong. Their nearly full-length sequences
      were also analysed. PARV4-like viruses were detected by PCR among 44.4 %
      (148/333) of porcine samples (including lymph nodes, liver, serum, nasopharyngeal
      and faecal samples), 13 % (4/32) of bovine spleen samples and 2 % (7/362) of
      human serum samples that were sent for human immunodeficiency virus and hepatitis
      C virus antibody tests. Three distinct parvoviruses were identified, including
      two novel parvoviruses, PHoV and BHoV, from porcine and bovine samples and PARV4
      from humans, respectively. Analysis of genome sequences from seven PHoV strains,
      from three BHoV strains and from one PARV4 strain showed that the two animal
      parvoviruses were most similar to PARV4 with 61.5-63 % nt identities and,
      together with PARV4 (HHoV), formed a distinct cluster within the family
      Parvoviridae. The three parvoviruses also differed from other parvoviruses by
      their relatively large predicted VP1 protein and the presence of a small unique
      conserved putative protein. Based on these results, we propose a separate genus,
      Hokovirus, to describe these three parvoviruses. The co-detection of porcine
      reproductive and respiratory syndrome virus, the agent associated with the recent
      'high fever' disease outbreaks in pigs in China, from our porcine samples
      warrants further investigation.

PMID- 18632955
TI  - Conserved archetypal configuration of the transcriptional control region during
      the course of BK polyomavirus evolution.
AB  - BK polyomavirus (BKV) is widespread among humans, asymptomatically infecting
      children and then persisting in renal tissue. The transcriptional control region
      (TCR) of the BKV genome is variable among clinical isolates. Thus, archetypal
      TCRs with a common basic configuration generally occur in BKV isolates from the
      urine of immunocompromised patients, but rearranged TCRs that possibly arise from
      the archetypal configuration have also been detected in clinical specimens. To
      examine the hypothesis that archetypal strains represent wild-type strains
      circulating in the human population (the archetype hypothesis), we analysed 145
      complete viral genomes amplified directly from the urine of non-immunocompromised
      individuals worldwide. These genomes included 82, three, two and 58 sequences
      classified as belonging to subtypes I, II, III and IV, respectively. Rearranged
      TCRs with long duplications or deletions were detected from two subtype I and two
      subtype IV genomes, but not from the other 141 genomes (thus, the TCRs of these
      genomes were judged to be archetypal). The variations in the archetypal TCRs were
      nucleotide substitutions and single-nucleotide deletions, most of which were
      unique to particular subtypes or subgroups. We confirmed that the four complete
      BKV genomes with rearranged TCRs did not form a unique lineage on a phylogenetic
      tree. Collectively, the findings demonstrate that the archetypal TCR
      configuration has been conserved during the evolution of BKV, providing support
      for the archetype hypothesis. Additionally, we suggest that 'archetype' should be
      used as a conceptual term that denotes a prototypical structure that can generate
      various rearranged TCRs during viral growth in vivo and in vitro.

PMID- 18632956
TI  - Protective immunity against porcine circovirus 2 by vaccination with ORF2-based
      DNA and subunit vaccines in mice.
AB  - The protective immune response against porcine circovirus 2 (PCV2) infection in
      mice was characterized using flow cytometric analysis (FCM), assays of antibody
      (of different IgG isotypes) and viraemia, and histopathological examination. An
      open reading frame 2 plasmid (pORF2) and the capsid protein (Cap) of PCV2 were
      used as DNA and subunit vaccines, respectively. In FCM analysis, although pORF2
      and Cap alone showed comparable efficacy in eliciting lymphoproliferative
      responses and Cap-specific CD4(+) T cells, pORF2 was superior to the Cap protein
      in triggering CD8(+) T cells. A virus neutralization assay showed that pORF2
      evoked stronger recall virus-neutralizing (VN) antibody responses than the Cap
      protein on PCV2 challenge. Correspondingly, VN antibody kinetics coincided with
      those of Cap-specific IgG2a, but not with the kinetics of IgG and IgG1. Following
      virus challenge, real-time PCR and histopathological analysis confirmed that only
      low viral DNA loads and mild microscopic lesions appeared in pORF2-immunized
      mice. These findings indicate that CD8(+) T cells and VN antibody responses
      correlating mainly with Cap-specific IgG2a play crucial roles in protecting
      against PCV2 infection, and that the protective immunity induced by the pORF2
      plasmid is superior to that induced by the PCV2 Cap protein.

PMID- 18632957
TI  - Identification and characterization of a novel envelope protein in Rana grylio
      virus.
AB  - Viral envelope proteins have been proposed to play significant roles in virus
      infection and assembly. In this study, an envelope protein gene, 53R, was cloned
      and characterized from Rana grylio virus (RGV), a member of the family
      Iridoviridae. Database searches found its homologues in all sequenced
      iridoviruses, and sequence alignment revealed several conserved structural
      features shared by virus capsid or envelope proteins: a myristoylation site, two
      predicted transmembrane domains and two invariant cysteine residues.
      Subsequently, RT-PCR and Western blot detection revealed that the transcripts
      encoding RGV 53R and the protein itself appeared late during infection of fathead
      minnow cells and that their appearance was blocked by viral DNA replication
      inhibitor, indicating that RGV 53R is a late expression gene. Moreover,
      immunofluorescence localization found an association of 53R with virus factories
      in RGV-infected cells, and this association was further confirmed by expressing a
      53R-GFP fusion protein in pEGFP-N3/53R-transfected cells. Furthermore, detergent
      extraction and Western blot detection confirmed that RGV 53R was associated with
      virion membrane. Therefore, the current data suggest that RGV 53R is a novel
      viral envelope protein and that it may play an important role in virus assembly.
      This is thought to be the first report on a viral envelope protein that is
      conserved in all sequenced iridoviruses.

PMID- 18632958
TI  - Functional analysis of the putative antiapoptotic genes, p49 and iap4, of
      Spodoptera litura nucleopolyhedrovirus with RNAi.
AB  - A homology search of a public database revealed that Spodoptera litura
      nucleopolyhedrovirus (SpltNPV) possesses two putative, antiapoptotic genes, p49
      and inhibitor of apoptosis 4 (iap4), but their function has not been investigated
      in its native host cells. In the present study, we used RNA interference (RNAi)
      to silence the expression of Splt-iap4 and Splt-p49, independently or together,
      to determine their roles during the SpltNPV life cycle. RT-PCR analysis and
      Western blot analysis showed the target gene expression had been knocked out in
      the SpltNPV-infected SpLi-221 cells after treatment with Splt-p49 or Splt-iap4
      double-stranded RNA (dsRNA), respectively, confirming that the two genes were
      effectively silenced. In SpltNPV-infected cells treated with Splt-p49 dsRNA,
      apoptosis was observed beginning at 14 h, and almost all cells had undergone
      apoptosis by 48 h. In contrast, budded virus production and polyhedra formation
      progressed normally in infected cells treated with Splt-iap4 dsRNA. Cell
      viability analysis showed that Splt-IAP4 had no synergistic effect on the
      inhibition of apoptosis of SpLi-221 cells induced by SpltNPV infection.
      Interestingly, after Splt-iap4 dsRNA treatment, cells did not congregate like
      those infected with SpltNPV in the early infection phase, implying an unknown
      role of baculovirus iap4. Our results determine that Splt-p49 is necessary to
      prevent apoptosis; however, Splt-iap4 has no antiapoptotic function during
      SpltNPV infection.

PMID- 18632959
TI  - The Npro product of classical swine fever virus interacts with IkappaBalpha, the
      NF-kappaB inhibitor.
AB  - Classical swine fever virus (CSFV) belongs to the genus Pestivirus and is the
      causative agent of classical swine fever, a haemorrhagic disease of pigs. The
      virus replicates in host cells without activating interferon (IFN) production and
      has been reported to be an antagonist of double-stranded RNA-induced apoptosis.
      The N-terminal protease (N(pro)) of CSFV is responsible for this evasion of the
      host innate immune response. In order to identify cellular proteins that interact
      with the N(pro) product of CSFV, a yeast two-hybrid screen of a human library was
      carried out, which identified IkappaBalpha, the inhibitor of NF-kappaB, a
      transcription factor involved in the control of apoptosis, the immune response
      and IFN production. The N(pro)-IkappaBalpha interaction was confirmed using yeast
      two-hybrid analysis and additional co-precipitation assays. It was also shown
      that N(pro) localizes to both the cytoplasmic and nuclear compartments in stably
      transfected cells and in CSFV-infected cells. Following stimulation by tumour
      necrosis factor alpha, PK-15 cell lines expressing N(pro) exhibited transient
      nuclear accumulation of pIkappaBalpha, but no effect of CSFV infection on
      IkappaBalpha localization or NF-kappaB p65 activation was observed.

PMID- 18632960
TI  - Differential reactivity of putative genotype 2 hepatitis C virus F protein
      between chronic and recovered infections.
AB  - To date, all studies regarding hepatitis C virus (HCV) F protein have been based
      on expression in vitro/in vivo of recombinant protein or monoclonal antibodies
      derived from genotype 1a or 1b sequences, but not from other genotypes. The
      objective of this study was to prepare a putative genotype 2 recombinant F
      protein and evaluate its reactivity in plasma from individuals with chronic HCV
      infection or who had recovered from infection. One genotype 2 strain was selected
      for F protein (F-2) and core expression in bacterial culture. An ELISA was
      developed and applied to samples from patients with chronic infection or
      recovered infection of various genotypes. The anti-F-2 response in 117 samples
      showed a significantly higher reactivity in chronic than in recovered HCV
      infected blood donors (P<0.001), but no difference was found among genotypes.
      However, the correlation between anti-F and anti-core was more significant in
      genotypes 1 and 2 than in genotype 3. Anti-F-2 titres were also significantly
      higher in chronic than in recovered individuals (P<0.0001). Antibody titres to
      recombinant genotype 2 core protein or to genotype 1 multiple proteins used in
      commercial anti-HCV assays paralleled the anti-F-2 end-point antibody titre. This
      study thus demonstrated the antigenicity of genotype 2 HCV F protein, although
      the exact location of the natural frameshift position remains unknown. The
      difference in anti-F-2 response between chronic and recovered infection, the
      cross-reactivity irrespective of genotype and the correlation of antibody
      response with structural and non-structural antigens suggest that the immune
      response to F protein is an integral part of the natural HCV infection.

PMID- 18632961
TI  - Genetic variation of St. Louis encephalitis virus.
AB  - St. Louis encephalitis virus (SLEV) has been regularly isolated throughout the
      Americas since 1933. Previous phylogenetic studies involving 62 isolates have
      defined seven major lineages (I-VII), further divided into 14 clades. In this
      study, 28 strains isolated in Texas in 1991 and 2001-2003, and three older,
      previously unsequenced strains from Jamaica and California were sequenced over
      the envelope protein gene. The inclusion of these new sequences, and others
      published since 2001, has allowed better delineation of the previously published
      SLEV lineages, in particular the clades of lineage II. Phylogenetic analysis of
      106 isolates identified 13 clades. All 1991 and 2001-2003 isolates from Nueces,
      Jefferson and Harris Counties (Texas Gulf Coast) group in clade IIB with other
      isolates from these counties isolated during the 1980s and 1990s. This lack of
      evidence for introduction of novel strains into the Texas Gulf Coast over a long
      period of time is consistent with overwintering of SLEV in this region. Two El
      Paso isolates, both from 2002, group in clade VA with recent Californian isolates
      from 1998-2001 and some South American strains with a broad temporal range.
      Overall, these data are consistent with multiple introductions of SLEV from South
      America into North America, and provide support for the hypothesis that in most
      situations, SLEV circulates within a locality, with occasional incursions from
      other areas. Finally, SLEV has much lower nucleotide (10.1 %) and amino acid
      variation (2.8 %) than other members of the Japanese encephalitis virus complex
      (maximum variation 24.6 % nucleotide and 11.8 % amino acid).

PMID- 18632962
TI  - A comparative cell biological analysis reveals only limited functional homology
      between the NS5A proteins of hepatitis C virus and GB virus B.
AB  - GB virus B (GBV-B) is the closest relative to hepatitis C virus (HCV) with which
      it shares a common genome organization, however, unlike HCV in humans, it
      generally causes an acute resolving hepatitis in New World monkeys. It is
      important to understand the factors regulating the different disease profiles of
      the two viruses and in this regard, as well as playing a key role in viral RNA
      replication, the HCV NS5A non-structural protein modulates a variety of host-cell
      signalling pathways. We have shown previously that HCV NS5A, expressed either
      alone, or in the context of the complete polyprotein, inhibits the Ras
      extracellular-signal-regulated kinase (Erk) pathway and activates the
      phosphoinositide 3-kinase (PI3K) pathway. In this report, we investigate whether
      these functions are shared by GBV-B NS5A. Immunofluorescence analysis revealed
      that a C-terminally FLAG-tagged GBV-B NS5A exhibited a punctate cytoplasmic
      distribution. However, unlike HCV NS5A, the GBV-B protein did not partially co
      localize with early endosomes. Utilizing a transient luciferase reporter system,
      we observed that GBV-B NS5A failed to inhibit Ras-Erk signalling, however GBV-B
      NS5A expression did result in the elevation of beta-catenin-dependent
      transcription via activation of the PI3K pathway. These effects of GBV-B and HCV
      NS5A on the PI3K and Ras-Erk pathways were confirmed in cells harbouring
      subgenomic replicons derived from the two viruses. Based on these data we
      speculate that the differential effects of the two NS5A proteins on cellular
      signalling pathways may contribute to the differences in the natural history of
      the two viruses.

PMID- 18632963
TI  - Distinctive pattern of sequence polymorphism in the NS3 protein of hepatitis C
      virus type 1b reflects conflicting evolutionary pressures.
AB  - Analysis of complete polyprotein-encoding sequences of hepatitis C virus genotype
      1b (HCV-1b) showed evidence not only of past purifying selection but also of
      abundant slightly deleterious non-synonymous variants subject to ongoing
      purifying selection. The NS3 protein (with protease and NTPase/helicase activity)
      revealed less evidence of purifying selection acting on the cytotoxic T cells
      (CTL) epitopes than did the other proteins, whereas outside the CTL epitopes NS3
      was more conserved than the other proteins. Moreover, NS3 showed a high incidence
      of forward-and-backward or parallel non-synonymous changes in CTL epitopes, as
      measured by the consistency index across the phylogeny of HCV-1b genomes computed
      at non-singleton non-synonymous polymorphic sites. This result implies that
      certain non-synonymous mutations have recurred frequently throughout the
      phylogeny in the codons encoding the epitopes in NS3. This pattern is most easily
      explained by the frequent re-occurrence of the same set of escape mutations in
      CTL epitopes of NS3, which are selectively favoured within hosts expressing the
      presenting class I major histocompatibility complex molecule, but are subject to
      purifying selection at the population level. The fact that this pattern is most
      strikingly observed in the case of NS3 suggests that the evolutionary conflict
      between immune escape and functional constraint on the protein is more acute in
      the case of NS3 than any of the other proteins of HCV-1b.

PMID- 18632964
TI  - Japanese encephalitis virus infection activates caspase-8 and -9 in a FADD
      independent and mitochondrion-dependent manner.
AB  - Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, replicates
      primarily at the endoplasmic reticulum and thereby triggers apoptosis of infected
      cells. This study investigated the hierarchical activation of the caspase network
      induced by JEV infection. It was found that JEV activated the initiators caspase
      8 and -9, as well as effector caspase-3, in infected baby hamster kidney and
      mouse neuroblastoma (N18) cells. In neuronal N18 cells, JEV infection triggered
      cytochrome c release from mitochondria, which in turn activated caspase-9 and -3.
      Treatment of JEV-infected N18 cells with cyclosporin A or ruthenium red, which
      attenuate mitochondrial injuries, blocked activation of caspase-9 or -3,
      typifying that, in neuronal cells, this apoptosis involves the mitochondrial
      pathway. Alternatively, in caspase-3-deficient MCF-7 cells, JEV persisted and
      readily triggered a typical apoptotic response, including cytochrome c release
      and full activation of caspase-9 and -8 along with caspase-6, indicating that JEV
      did not require caspase-3 to manifest caspase-8 activation and apoptosis.
      Interestingly, a Fas-associated death-domain-containing protein (FADD) dominant
      negative mutant, which interfered with transmission of the extracellular death
      signals into cells through the Fas/tumour necrosis factor (TNF) receptor, failed
      to block JEV-induced apoptosis and caspase-8 activation, implying that receptor
      oligomerization of the Fas/TNF pathway might not participate in JEV-induced
      apoptosis. Taken together, these results illustrate that JEV infection triggers
      caspase cascades involving the initiators caspase-8 and -9, probably through FADD
      independent but mitochondrion-dependent pathways.

PMID- 18632965
TI  - Restricted Semliki Forest virus replication in perforin and Fas-ligand double
      deficient mice.
AB  - Previously, we have shown that mice defective in granule exocytosis and/or
      Fas.L/Fas-mediated cytolytic pathways are significantly more resistant to
      alphavirus, Semliki Forest virus (SFV), infection compared with wild-type mice.
      Here, we evaluated SFV replication in different tissues of mice defective in both
      cytolytic pathways (perf(-/-)xgld) relative to that in wild-type counterparts and
      found that viral replication in perf(-/-)xgld mice is remarkably restricted.
      Although the mechanism responsible for this observation is yet to be established,
      the lower virus titres found in these mice indicate that the role of cytolytic
      effector molecules in antiviral immunity needs to be re-evaluated.

PMID- 18632966
TI  - A226V mutation in virus during the 2007 chikungunya outbreak in Kerala, India.
AB  - Kerala State in India was gripped by a renewed and widespread outbreak of
      Chikungunya virus (CHIKV) infection during 2007. Here, we report the A226V
      mutation in the glycoprotein envelope 1 (E1) gene of the virus among isolates
      collected from the three worst-affected districts of the state during this
      outbreak. This mutation had already been suggested to be directly responsible for
      a significant increase in CHIKV infectivity in Aedes albopictus. The badly
      affected districts in Kerala State during 2007 have abundant rubber plantations,
      which supported prolific breeding of Ae. albopictus mosquitoes. The abundance of
      Ae. albopictus in the region and molecular evolution of CHIKV may be contributing
      factors for the renewed epidemic of chikungunya fever during 2007.

PMID- 18632967
TI  - An enterovirus strain isolated from diabetic child belongs to a genetic
      subcluster of echovirus 11, but is also neutralised with monotypic antisera to
      coxsackievirus A9.
AB  - An enterovirus strain (designated D207) isolated from a Slovakian diabetic child
      and originally serotyped as coxsackievirus A9 (CAV-9) was found to cause rapid
      cytolysis coinciding with severe functional damage of the surviving cells in
      primary cultures of human pancreatic islets. This finding prompted us to clone
      the isolate for full-length genome sequencing and molecular characterization as
      the prototype strain of CAV-9 is known to cause only minimal damage to insulin
      producing beta-cells. Based on capsid-coding sequence comparisons, the isolate
      turned out to be echovirus 11 (E-11). Phylogenetic analyses demonstrated that E
      11/D207 was closely related to a specific subgroup B of E-11 strains known to
      cause uveitis. To study further antigenic properties of isolate E-11/D207 and
      uveitis-causing E-11 strains, neutralization experiments were carried out with
      CAV-9- and E-11-specific antisera. Unlike the prototype strains, the isolate E
      11/D207 and uveitis-causing E-11 strains were well neutralized with both CAV-9-
      and E-11-specific antisera. Attempts to identify recombination of the capsid
      coding sequences as a reason for double-reactivity using the Simplot analysis
      failed to reveal major transferred motifs. However, peptide scanning technique
      was able to identify antigenic regions of capsid proteins of E-11/D207 as well as
      regions cross-reacting with an antiserum raised to CAV-9. Thus, double
      specificity of E-11/D207 seems to be a real characteristic shared by the
      phylogenetically closely related virus strains in the genetic subgroup B of E-11.

PMID- 18632968
TI  - Severe acute respiratory syndrome coronavirus 3a protein activates the
      mitochondrial death pathway through p38 MAP kinase activation.
AB  - The molecular mechanisms governing severe acute respiratory syndrome coronavirus
      induced pathology are not fully understood. Virus infection and some individual
      viral proteins, including the 3a protein, induce apoptosis. However, the cellular
      targets leading to 3a protein-mediated apoptosis have not been fully
      characterized. This study showed that the 3a protein modulates the mitochondrial
      death pathway in two possible ways. Activation of caspase-8 through extrinsic
      signal(s) caused Bid activation. In the intrinsic pathway, there was activation
      of caspase-9 and cytochrome c release from the mitochondria. This was the result
      of increased Bax oligomerization and higher levels of p53 in 3a protein
      expressing cells, which depended on the activation of p38 MAP kinase (MAPK) in
      these cells. For p38 activation and apoptosis induction, the 3a cytoplasmic
      domain was sufficient. In direct Annexin V staining assays, the 3a protein
      expressing cells showed increased apoptosis that was attenuated with the p38 MAPK
      inhibitor SB203580. A block in nuclear translocation of the STAT3 transcription
      factor in cells expressing the 3a protein was also observed. These results have
      been used to present a model of 3a-mediated apoptosis.

PMID- 18632969
TI  - Detection of four genetic subgroup-specific antibodies to human metapneumovirus
      attachment (G) protein in human serum.
AB  - Human metapneumovirus (hMPV) strains are classified into two genetic groups, A
      and B, each of which is further divided in two genetic subgroups, A1, A2, B1 and
      B2. hMPV encodes two major surface glycoproteins, the fusion (F) and attachment
      (G) proteins, which may be immunogenic and protective antigens. Although the
      amino acid sequences of hMPV F protein are highly conserved, those of the G
      protein are highly variable with low amino acid identity between the two groups.
      To address the antigenic variation between the genetic subgroups, we developed an
      immunofluorescence assay (IFA) method using Trichoplusia ni (Tn5) insect cells
      infected with each recombinant baculovirus-expressed hMPV G (Bac-G) protein of
      the four genetic subgroups. The titre of each antibody to the four Bac-G proteins
      was measured by the IFA in 12 paired serum samples obtained from children
      infected with hMPV of each genetic subgroup. Although 11 of the 12 acute-phase
      serum samples in paired samples were negative for the antibody to any Bac-G
      proteins, all of the convalescent-phase serum samples in those paired samples
      were positive for the antibody to only one of the four Bac-G proteins of the
      infecting genotype of hMPV. Since the antibody response to hMPV G protein was
      transient and genetic subgroup-specific without cross-reactivity, four genetic
      subgroups on the basis of hMPV G protein could be identified as different
      serotypes. This assay may be useful for the study of immune responses of humans
      to different hMPV strains, especially for clarifying the risk of reinfection with
      hMPV.

PMID- 18632971
TI  - Molecular diversity and phylogeny of Hantaan virus in Guizhou, China: evidence
      for Guizhou as a radiation center of the present Hantaan virus.
AB  - To gain further insight into the molecular epidemiology of Hantaan virus (HTNV)
      in Guizhou, China, rodents were captured in this region in 2004 and 2005. In
      addition, serum samples were collected from four patients. Ten hantaviruses were
      isolated successfully in cell culture from four humans, two Apodemus agrarius,
      three Rattus norvegicus and one Rattus nitidus. The nucleotide sequences for
      their small (S), medium (M) and partial large (L) segments were determined.
      Phylogenetic analysis of the S and M segment sequences revealed that all of these
      isolates belong to the species HTNV, suggesting a spillover of HTNV from A.
      agrarius to Rattus rats. All available isolates from Guizhou were divided into
      four distinct groups either in the S segment tree or in the M segment tree. The
      clustering pattern of these isolates in the S segment tree was not in agreement
      with that in the M or L segment tree, showing that genetic reassortment between
      HTNV had occurred naturally. Analysis of the S segment sequences from available
      HTNV strains indicated that they formed three clades. The first clade, which
      comprised only viruses from Guizhou, was the outgroup of clades II and III. The
      viruses in the second clade were found in Guizhou and mainly in the far-east
      Asian region, including China. However, the viruses in the third clade were found
      in most areas of China, including Guizhou, in which haemorrhagic fever with renal
      syndrome (HFRS) is endemic. Our results reveal that the highest genetic diversity
      of HTNV is in a limited geographical region of Guizhou, and suggest that Guizhou
      might be a radiation centre of the present form of HTNV.

PMID- 18632972
TI  - Susceptibility of North American big brown bats (Eptesicus fuscus) to infection
      with European bat lyssavirus type 1.
AB  - The aim of this study was to determine the susceptibility of insectivorous bats
      (using the big brown bat as a model) to infection with European bat lyssavirus
      type 1a (EBLV-1a), to assess the dynamics of host immune responses and to
      evaluate the opportunity for horizontal viral transmission within colonies. Two
      isolates of EBLV-1a, originating from Slovakia (EBLV-1aSK) and Germany (EBLV
      1aGE), were tested. Four different routes of inoculation were used with isolate
      EBLV-1aSK [10(4.8) mouse intracerebral median lethal dose (MICLD(50)) in 50 mul]:
      intramuscular (i.m.) in the deltoid area or masseter region, per os (p.o.) and
      intradermal (i.d.) scratches. Isolate EBLV-1aGE (10(3.2) and 10(2.2) MICLD(50) in
      20 mul) was inoculated via the intranasal (i.n.), i.m. (low- and high-dose
      groups, into pectoral muscles); p.o. and intracerebral (i.c.) routes. None of the
      bats infected by the i.n., p.o. or i.d. route with either virus isolate developed
      disease during the experiments (91 or 120 days, respectively). Incubation periods
      were 9-12 days for i.c.-inoculated bats (66 % mortality), 12-33 days for bats
      inoculated i.m. with the higher dose (23-50 % mortality) and 21-58 days in bats
      inoculated i.m. with the lower dose of virus (57 % mortality). Virus or viral RNA
      in bat saliva was detected occasionally, as early as 37 days before death. All
      i.d.-inoculated and the majority of i.m.-inoculated bats seroconverted within 7
      10 days of inoculation. These observations suggest that exposure of bats to
      varying doses of EBLV-1 from rabid conspecifics via natural (i.d.) routes could
      lead to an abortive infection and serve as a natural mode of immunization
      resulting in the presence of virus-neutralizing antibodies in free-ranging bats.

PMID- 18632970
TI  - Role of retinoic acid inducible gene-I in human metapneumovirus-induced cellular
      signalling.
AB  - Human metapneumovirus (HMPV) is a recently discovered pathogen that causes a
      significant proportion of respiratory infections in young infants, the elderly
      and immunocompromised patients. Very little is known regarding the cellular
      signalling elicited by this virus in airway epithelial cells, the target of HMPV
      infection. In this study, we investigated the role of the RNA helicases retinoic
      acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene-5 (MDA
      5) as the main pattern recognition receptors (PRRs) involved in viral detection
      and subsequent expression of proinflammatory and antiviral genes. HMPV infection
      readily induced RIG-I and MDA-5 gene and protein expression in A549 cells, a type
      II-like alveolar epithelial cell line. Expression of dominant-negative (DN) RIG-I
      or downregulation of RIG-I gene expression using small interfering RNA (siRNA)
      significantly decreased HMPV-induced beta interferon (IFN-beta), interleukin (IL)
      8 and RANTES gene transcription, by inhibiting viral-induced activation of
      nuclear factor (NF)-kappaB and interferon regulatory factor (IRF), leading to
      enhanced viral replication. On the other hand, MDA-5 did not seem to play a
      significant role in HMPV-induced cellular responses. Mitochondrial antiviral
      signalling protein (MAVS), an adaptor protein linking both RIG-I and MDA-5 to
      downstream activation of IRF-3 and NF-kappaB, was also necessary for HMPV-induced
      cellular signalling. Expression of a DN MAVS significantly reduced IFN-beta and
      chemokine gene transcription, by inhibiting NF-kappaB- and IRF-dependent gene
      transcription, in response to HMPV infection. Our results show that HMPV
      activates the RIG-I-MAVS signalling pathway in airway epithelial cells, leading
      to the expression of important proinflammatory and antiviral molecules involved
      in the innate immune response to viruses.

PMID- 18632973
TI  - Binding of equine infectious anemia virus to the equine lentivirus receptor-1 is
      mediated by complex discontinuous sequences in the viral envelope gp90 protein.
AB  - The identification and characterization of a functional cellular receptor for
      equine infectious anemia virus (EIAV), designated equine lentivirus receptor-1
      (ELR1), a member of the tumour necrosis factor receptor protein family, has been
      reported previously [Zhang, B. et al. (2005). Proc Natl Acad Sci U S A, 102 ,
      9918-9923]. The finding of a single receptor for EIAV is distinct from feline,
      simian and human immunodeficiency viruses, which typically utilize two co
      receptors for infection, but is similar to avian and murine oncoviruses, which
      use single receptors. This study sought to determine ELR1-binding domains of EIAV
      gp90. Towards this goal, a GFP-tagged gp90 fusion protein (gp90GFP) expression
      vector was constructed and a specific cell-cell binding assay was developed to
      measure EIAV gp90 binding to ELR1. Using these assays, the receptor-binding
      properties of 41 gp90GFP mutants were evaluated, each with a sequential
      replacement 11 aa linear epitope peptide from the vesicular stomatitis virus
      glycoprotein (VSV-G tag), as well as eight mutants containing individual gp90
      variable-domain deletions. The results of these studies demonstrated that, in
      general, gp90 constructs containing substitutions or deletions in the N-terminal
      third of gp90 retained their receptor-binding activity. In contrast, segment
      substitutions or deletions in the C-terminal two-thirds of gp90 eliminated
      receptor-binding activity. Thus, these results reveal for the first time that the
      ELR1-binding domains of EIAV gp90 are located in the C-terminal two-thirds of
      EIAV gp90, apparently as a complex of discontinuous determinants.

PMID- 18632974
TI  - Field evaluation of a gag/env heteroduplex mobility assay for genetic subtyping
      of small-ruminant lentiviruses.
AB  - Small-ruminant lentiviruses (SRLVs) display a high genetic diversity and are
      currently classified into five genotypes and an increasing number of subtypes.
      The co-circulation of subtypes in restricted geographical regions, combined with
      the occurrence of cross-species infection, suggests the need for development of a
      large-scale screening methodology for rapid monitoring of the prevalence of the
      various genetic subtypes and their genetic evolution. Here, a heteroduplex
      mobility assay (HMA) was developed for the rapid identification of group B
      subtypes. The assay was validated for both the p14 nucleocapsid-coding region of
      the gag gene and the V1-V2 region of the env gene using a panel of reference
      standards and was applied to the genetic subtyping of SRLV field isolates from
      five mixed flocks in France. Subtyping of 75 blood samples using the env HMA
      revealed a preferential distribution of subtypes B1 and B2 in sheep and goats,
      despite direct evidence for interspecies transmission of both subtypes. Adding
      the gag HMA to the env HMA provided evidence for dual infection and putative
      recombination between subtypes B1 and B2 in five goats, and between groups A and
      B in one sheep. Phylogenetic analysis revealed that 100 % (23/23) and 96.7 %
      (30/31) of samples were correctly classified using the gag and env HMAs,
      respectively. These results indicate that dual infection and recombination may be
      a significant source of new variation in SRLV and provide a useful tool for the
      rapid genetic subtyping of SRLV isolates, which could be relevant for the
      development of more accurate diagnosis of prevalent SRLV strains in different
      countries.

PMID- 18632975
TI  - Disassembly of African cassava mosaic virus.
AB  - The plant-infecting geminiviruses encapsidate their single-stranded DNA genome in
      characteristic twinned particles that are unique among viruses. These particles
      are formed by joining two incomplete T=1 icosahedra. African cassava mosaic
      virions were purified by density-gradient centrifugation from infected Nicotiana
      benthamiana plants and analysed for their stability with respect to pH changes
      and heat treatment by using electron microscopy. Negative staining and rotary
      shadowing revealed stable virions as well as isolated capsomeres between pH 4.0
      and 8.5. At pH 9.0 and above, particles disintegrated, whereas they mainly
      aggregated at a pH below 6.0. Heating the preparations to 55 degrees C and above
      resulted in the complete loss of any discernible structure. A low proportion
      (approx. 10 %) of particles ejected their DNA within the pH range of 6.0-8.5.
      Most virions released their DNA at the top (15.9 %) or the shoulder (71.4 %) of
      the twin particles and only 12.7 % at the waist. Compared with the expected
      numbers of pentameric capsomeres at the top (9 %), the shoulder (45.5 %) or the
      waist (45.5 %), the results revealed a preferential DNA release from the top and
      shoulder of the geminate particle.

PMID- 18632976
TI  - Small deletions in the potato leafroll virus readthrough protein affect particle
      morphology, aphid transmission, virus movement and accumulation.
AB  - Potato leafroll virus (PLRV) capsid comprises 180 coat protein (CP) subunits,
      with some percentage containing a readthrough domain (RTD) extension located on
      the particle's surface. The RTD N terminus is highly conserved in luteovirids and
      this study sought to identify biologically active sites within this region of the
      PLRV RTD. Fourteen three-amino-acid-deletion mutants were generated from a cloned
      infectious PLRV cDNA and delivered to plants by Agrobacterium inoculations. All
      mutant viruses accumulated locally in infiltrated tissues and expressed the
      readthrough protein (RTP) containing the CP and RTD sequences in plant tissues;
      however, when purified, only three mutant viruses incorporated the RTP into the
      virion. None of the mutant viruses were aphid transmissible, but the viruses
      persisted in aphids for a period sufficient to allow for virus transmission.
      Several mutant viruses were examined further for systemic infection in four host
      species. All mutant viruses, regardless of RTP incorporation, moved systemically
      in each host, although they accumulated at different rates in systemically
      infected tissues. The biological properties of the RTP are sensitive to
      modifications in both the RTD conserved and variable regions.

PMID- 18632977
TI  - HC-Pro protein of sugar cane mosaic virus interacts specifically with maize
      ferredoxin-5 in vitro and in planta.
AB  - Symptom development of a plant viral disease is a result of molecular
      interactions between the virus and its host plant; thus, the elucidation of
      specific interactions is a prerequisite to reveal the mechanism of viral
      pathogenesis. Here, we show that the chloroplast precursor of ferredoxin-5 (Fd V)
      from maize (Zea mays) interacts with the multifunctional HC-Pro protein of sugar
      cane mosaic virus (SCMV) in yeast, Nicotiana benthamiana cells and maize
      protoplasts. Our results demonstrate that the transit peptide rather than the
      mature protein of Fd V precursor could interact with both N-terminal (residues 1
      100) and C-terminal (residues 301-460) fragments, but not the middle part
      (residues 101-300), of HC-Pro. In addition, SCMV HC-Pro interacted only with Fd
      V, and not with the other two photosynthetic ferredoxin isoproteins (Fd I and Fd
      II) from maize plants. SCMV infection significantly downregulated the level of Fd
      V mRNA in maize plants; however, no obvious changes were observed in levels of Fd
      I and Fd II mRNA. These results suggest that SCMV HC-Pro interacts specifically
      with maize Fd V and that this interaction may disturb the post-translational
      import of Fd V into maize bundle-sheath cell chloroplasts, which could lead to
      the perturbation of chloroplast structure and function.

PMID- 18632978
TI  - Delivery of single-chain antibodies (scFvs) directed against the 37/67 kDa
      laminin receptor into mice via recombinant adeno-associated viral vectors for
      prion disease gene therapy.
AB  - The 37/67 kDa laminin receptor (LRP/LR) acts as a receptor for prions providing a
      promising target for the treatment of prion diseases. Recently, we selected anti
      LRP/LR single-chain antibodies (scFvs) and proved a reduction of the peripheral
      PrP(Sc) propagation by passive immunotransfer into scrapie-infected mice. Here,
      we report the development of an in vivo gene delivery system based on adeno
      associated virus (AAV) vectors expressing scFvs-S18 and -N3 directed against
      LRP/LR. Transduction of neuronal and non-neuronal cells with recombinant (r)AAV
      serotype 2 vectors encoding scFv-S18, -N3 and -C9 verified the efficient
      secretion of the antibodies. These vectors were administered via stereotactic
      intracerebral microinjection into the hippocampus of C57BL/6 mice, followed by
      intracerebral inoculation with 10 % RML at the same site 2 weeks post-injection
      of rAAV. After 90 days post-infection, scFv-S18 and -N3 expression resulted in
      the reduction of peripheral PrP(Sc) propagation by approximately 60 and 32 %,
      respectively, without a significant prolongation of incubation times and
      survival. Proof of rAAV vector DNA in spleen samples by real-time PCR strongly
      suggests a transport or trafficking of rAAV from the brain to the spleen,
      resulting in rAAV-mediated expression of scFv followed by reduced PrP(Sc) levels
      in the spleen most likely due to the blockage of the prion receptor LRP/LR by
      scFv.

PMID- 18632980
TI  - Translationally repressed mRNA transiently cycles through stress granules during
      stress.
AB  - In mammals, repression of translation during stress is associated with the
      assembly of stress granules in the cytoplasm, which contain a fraction of
      arrested mRNA and have been proposed to play a role in their storage. Because
      physical contacts are seen with GW bodies, which contain the mRNA degradation
      machinery, stress granules could also target arrested mRNA to degradation. Here
      we show that contacts between stress granules and GW bodies appear during stress
      granule assembly and not after a movement of the two preassembled structures.
      Despite this close proximity, the GW body proteins, which in some conditions
      relocalize in stress granules, come from cytosol rather than from adjacent GW
      bodies. It was previously reported that several proteins actively traffic in and
      out of stress granules. Here we investigated the behavior of mRNAs. Their
      residence time in stress granules is brief, on the order of a minute, although
      stress granules persist over a few hours after stress relief. This short transit
      reflects rapid return to cytosol, rather than transfer to GW bodies for
      degradation. Accordingly, most arrested mRNAs are located outside stress
      granules. Overall, these kinetic data do not support a direct role of stress
      granules neither as storage site nor as intermediate location before degradation.

PMID- 18632979
TI  - Epidermal growth factor-induced enhancement of glioblastoma cell migration in 3D
      arises from an intrinsic increase in speed but an extrinsic matrix- and
      proteolysis-dependent increase in persistence.
AB  - Epidermal growth factor (EGF) receptor-mediated cell migration plays a vital role
      in invasion of many tumor types. EGF receptor ligands increase invasiveness in
      vivo, but it remains unclear how consequent effects on intrinsic cell motility
      behavior versus effects on extrinsic matrix properties integrate to result in net
      increase of translational speed and/or directional persistence of migration in a
      3D environment. Understanding this convolution is important for therapeutic
      targeting of tumor invasion, as key regulatory pathways for intrinsic versus
      extrinsic effects may not be coincident. Accordingly, we have undertaken a
      quantitative single-cell imaging study of glioblastoma cell movement in 3D
      matrices and on 2D substrata across a range of collagen densities with systematic
      variation of protease-mediated matrix degradation. In 3D, EGF induced a mild
      increase in cell speed and a strong increase in directional persistence, the
      latter depending heavily on matrix density and EGF-stimulated protease activity.
      In contrast, in 2D, EGF induced a similarly mild increase in speed but conversely
      a decrease in directional persistence (both independent of protease activity).
      Thus, the EGF-enhanced 3D tumor cell migration results only partially from cell
      intrinsic effects, with override of cell-intrinsic persistence decrease by
      protease-mediated cell-extrinsic reduction of matrix steric hindrance.

PMID- 18632981
TI  - Consequences of individual N-glycan deletions and of proteasomal inhibition on
      secretion of active BACE.
AB  - BACE is an aspartic protease involved in the production of a toxic peptide
      accumulating in the brain of Alzheimer's disease patients. After attainment of
      the native structure in the endoplasmic reticulum (ER), BACE is released into the
      secretory pathway. To better understand the mechanisms regulating protein
      biogenesis in the mammalian ER, we determined the fate of five variants of
      soluble BACE with 4, 3, 2, 1, or 0 N-linked glycans. The number of N-glycans
      displayed on BACE correlated directly with folding and secretion rates and with
      the yield of active BACE harvested from the cell culture media. Addition of a
      single N-glycan was sufficient to recruit the calnexin chaperone system and/or
      for oligosaccharide de-glucosylation by the ER-resident alpha-glucosidase II.
      Addition of 1-4 N-glycans progressively enhanced the dissociation rate from BiP
      and reduced the propensity of newly synthesized BACE to enter aberrant soluble
      and insoluble aggregates. Finally, inhibition of the proteasome increased the
      yield of active BACE. This shows that active protein normally targeted for
      destruction can be diverted for secretion, as if for BACE the quality control
      system would be acting too stringently in the ER lumen, thus causing loss of
      functional polypeptides.

PMID- 18632982
TI  - p120-catenin is a key component of the cadherin-gamma-secretase supercomplex.
AB  - In this work, we show several previously unknown features of p120-catenin in a
      cadherin-catenin complex that are critical for our understanding of cadherin
      based adhesion and signaling. We show that in human epithelial A-431 cells,
      nearly all p120 molecules engage in high-affinity interaction with E-cadherin
      catenin complexes located at the cellular surface. p120 is positioned in
      proximity to alpha-catenin in the complex with cadherin. These findings suggest a
      functional cooperation between p120 and alpha-catenin in cadherin-based adhesion.
      A low level of cadherin-free p120 molecules, in contrast, could facilitate p120
      dependent signaling. Finally, we present compelling evidence that p120 is a key
      linker cementing the E-cadherin-catenin complex with the transmembrane protease
      gamma-secretase. The cell-cell contact location of this supercomplex makes it an
      important candidate for conducting different signals that rely on gamma-secretase
      proteolytic activity.

PMID- 18632983
TI  - Dual regulation of Mad2 localization on kinetochores by Bub1 and Dam1/DASH that
      ensure proper spindle interaction.
AB  - The spindle assembly checkpoint monitors the state of spindle-kinetochore
      interaction to prevent premature onset of anaphase. Although checkpoint proteins,
      such as Mad2, are localized on kinetochores that do not interact properly with
      the spindle, it remains unknown how the checkpoint proteins recognize
      abnormalities in spindle-kinetochore interaction. Here, we report that Mad2
      localization on kinetochores in fission yeast is regulated by two partially
      overlapping but distinct pathways: the Dam1/DASH and the Bub1 pathways. We show
      that Mad2 is localized on "unattached" as well as "tensionless" kinetochores. Our
      observations suggest that Bub1 is required for Mad2 to detect tensionless
      kinetochores, whereas Dam1/DASH is crucial for Mad2 to detect unattached
      kinetochores. In cells lacking both Bub1 and Dam1/DASH, Mad2 localization on
      kinetochores is diminished, and mitotic progression appears to be accelerated
      despite the frequent occurrence of abnormal chromosome segregation. Furthermore,
      we found that Dam1/DASH is required for promotion of spindle association with
      unattached kinetochores. In contrast, there is accumulating evidence that Bub1 is
      involved in resolution of erroneous spindle attachment on tensionless
      kinetochores. These pathways may act as molecular sensors determining the state
      of spindle association on each kinetochore, enabling proper regulation of the
      checkpoint activation as well as promotion/resolution of spindle attachment.

PMID- 18632984
TI  - Transcription-coupled DNA double-strand breaks are mediated via the nucleotide
      excision repair and the Mre11-Rad50-Nbs1 complex.
AB  - The cellular activity of Yondelis (trabectedin, Ecteinascidin 743, Et743) is
      known to depend on transcription-coupled nucleotide excision repair (TCR).
      However, the subsequent cellular effects of Et743 are not fully understood. Here
      we show that Et743 induces both transcription- and replication-coupled DNA double
      strand breaks (DSBs) that are detectible by neutral COMET assay and as gamma-H2AX
      foci that colocalize with 53BP1, Mre11, Ser(1981)-pATM, and Thr(68)-pChk2. The
      transcription coupled-DSBs (TC-DSBs) induced by Et743 depended both on TCR and
      Mre11-Rad50-Nbs1 (MRN) and were associated with DNA-PK-dependent gamma-H2AX foci.
      In contrast to DNA-PK, ATM phosphorylated H2AX both in NER-proficient and 
      deficient cells, but its full activation was dependent on H2AX as well as DNA-PK,
      suggesting a positive feedback loop: DNA-PK-gamma-H2AX-ATM. Knocking-out H2AX or
      inactivating DNA-PK reduced Et743's antiproliferative activity, whereas ATM and
      MRN tended to act as survival factors. Our results highlight the interplays
      between ATM and DNA-PK and their impacts on H2AX phosphorylation and cell
      survival. They also suggest that gamma-H2AX may serve as a biomarker in patients
      treated with Et743 and that molecular profiling of tumors for TCR, MRN, ATM, and
      DNA-PK might be useful to anticipate tumor response to Et743 treatment.

PMID- 18632986
TI  - Caenorhabditis elegans teneurin, ten-1, is required for gonadal and pharyngeal
      basement membrane integrity and acts redundantly with integrin ina-1 and
      dystroglycan dgn-1.
AB  - The Caenorhabditis elegans teneurin ortholog, ten-1, plays an important role in
      gonad and pharynx development. We found that lack of TEN-1 does not affect
      germline proliferation but leads to local basement membrane deficiency and early
      gonad disruption. Teneurin is expressed in the somatic precursor cells of the
      gonad that appear to be crucial for gonad epithelialization and basement membrane
      integrity. Ten-1 null mutants also arrest as L1 larvae with malformed pharynges
      and disorganized pharyngeal basement membranes. The pleiotropic phenotype of ten
      1 mutant worms is similar to defects found in basement membrane receptor mutants
      ina-1 and dgn-1 as well as in the mutants of the extracellular matrix component
      laminin, epi-1. We show that the ten-1 mutation is synthetic lethal with
      mutations of genes encoding basement membrane components and receptors due to
      pharyngeal or hypodermal defects. This indicates that TEN-1 could act redundantly
      with integrin INA-1, dystroglycan DGN-1, and laminin EPI-1 in C. elegans
      development. Moreover, ten-1 deletion sensitizes worms to loss of nidogen nid-1
      causing a pharynx unattached phenotype in ten-1;nid-1 double mutants. We conclude
      that TEN-1 is important for basement membrane maintenance and/or adhesion in
      particular organs and affects the function of somatic gonad precursor cells.

PMID- 18632985
TI  - HDAC4 promotes growth of colon cancer cells via repression of p21.
AB  - The class II Histone deacetylase (HDAC), HDAC4, is expressed in a tissue-specific
      manner, and it represses differentiation of specific cell types. We demonstrate
      here that HDAC4 is expressed in the proliferative zone in small intestine and
      colon and that its expression is down-regulated during intestinal differentiation
      in vivo and in vitro. Subcellular localization studies demonstrated HDAC4
      expression was predominantly nuclear in proliferating HCT116 cells and
      relocalized to the cytoplasm after cell cycle arrest. Down-regulating HDAC4
      expression by small interfering RNA (siRNA) in HCT116 cells induced growth
      inhibition and apoptosis in vitro, reduced xenograft tumor growth, and increased
      p21 transcription. Conversely, overexpression of HDAC4 repressed p21 promoter
      activity. p21 was likely a direct target of HDAC4, because HDAC4 down-regulation
      increased p21 mRNA when protein synthesis was inhibited by cycloheximide. The
      importance of p21 repression in HDAC4-mediated growth promotion was demonstrated
      by the failure of HDAC4 down-regulation to induce growth arrest in HCT116 p21
      null cells. HDAC4 down-regulation failed to induce p21 when Sp1 was functionally
      inhibited by mithramycin or siRNA-mediated down-regulation. HDAC4 expression
      overlapped with that of Sp1, and a physical interaction was demonstrated by
      coimmunoprecipitation. Chromatin immunoprecipitation (ChIP) and sequential ChIP
      analyses demonstrated Sp1-dependent binding of HDAC4 to the proximal p21
      promoter, likely directed through the HDAC4-HDAC3-N-CoR/SMRT corepressor complex.
      Consistent with increased transcription, HDAC4 or SMRT down-regulation resulted
      in increased histone H3 acetylation at the proximal p21 promoter locus. These
      studies identify HDAC4 as a novel regulator of colon cell proliferation through
      repression of p21.

PMID- 18632987
TI  - Interaction between tumor suppressor adenomatous polyposis coli and topoisomerase
      IIalpha: implication for the G2/M transition.
AB  - The tumor suppressor adenomatous polyposis coli (APC) is implicated in regulating
      multiple stages of the cell cycle. APC participation in G1/S is attributed to its
      recognized role in Wnt signaling. APC function in the G2/M transition is less
      well established. To identify novel protein partners of APC that regulate the
      G2/M transition, APC was immunoprecipitated from colon cell lysates and
      associated proteins were analyzed by matrix-assisted laser desorption
      ionization/time of flight (MALDI-TOF). Topoisomerase IIalpha (topo IIalpha) was
      identified as a potential binding partner of APC. Topo IIalpha is a critical
      regulator of G2/M transition. Evidence supporting an interaction between
      endogenous APC and topo IIalpha was obtained by coimmunoprecipitation,
      colocalization, and Forster resonance energy transfer (FRET). The 15-amino acid
      repeat region of APC (M2-APC) interacted with topo IIalpha when expressed as a
      green fluorescent protein (GFP)-fusion protein in vivo. Although lacking defined
      nuclear localization signals (NLS) M2-APC predominantly localized to the nucleus.
      Furthermore, cells expressing M2-APC displayed condensed or fragmented nuclei,
      and they were arrested in the G2 phase of the cell cycle. Although M2-APC
      contains a beta-catenin binding domain, biochemical studies failed to implicate
      beta-catenin in the observed phenotype. Finally, purified recombinant M2-APC
      enhanced topo IIalpha activity in vitro. Together, these data support a novel
      role for APC in the G2/M transition, potentially through association with topo
      IIalpha.

PMID- 18632988
TI  - YY1 protects cardiac myocytes from pathologic hypertrophy by interacting with
      HDAC5.
AB  - YY1 is a transcription factor that can repress or activate the transcription of a
      variety of genes. Here, we show that the function of YY1 as a repressor in
      cardiac myocytes is tightly dependent on its ability to interact with histone
      deacetylase 5 (HDAC5). YY1 interacts with HDAC5, and overexpression of YY1
      prevents HDAC5 nuclear export in response to hypertrophic stimuli and the
      increase in cell size and re-expression of fetal genes that accompany
      pathological cardiac hypertrophy. Knockdown of YY1 results in up-regulation of
      all genes present during fetal development and increases the cell size of
      neonatal cardiac myocytes. Moreover, overexpression of a YY1 deletion construct
      that does not interact with HDAC5 results in transcription activation, suggesting
      that HDAC5 is necessary for YY1 function as a transcription repressor. In support
      of this relationship, we show that knockdown of HDAC5 results in transcription
      activation by YY1. Finally, we show that YY1 interaction with HDAC5 is dependent
      on the HDAC5 phosphorylation domain and that overexpression of YY1 reduces HDAC5
      phosphorylation in response to hypertrophic stimuli. Our results strongly suggest
      that YY1 functions as an antihypertrophic factor by preventing HDAC5 nuclear
      export and that up-regulation of YY1 in human heart failure may be a protective
      mechanism against pathological hypertrophy.

PMID- 18632989
TI  - Dual acylation and lipid raft association of Src-family protein tyrosine kinases
      are required for SDF-1/CXCL12-mediated chemotaxis in the Jurkat human T cell
      lymphoma cell line.
AB  - Chemokines play pivotal roles in regulating a wide variety of biological
      processes by modulating cell migration and recruitment. Deregulation of chemokine
      signaling can alter cell recruitment, contributing to the pathogenic states
      associated with autoimmune disease, inflammatory disorders, and sepsis. During
      chemotaxis, lipid rafts and their resident signaling molecules have been
      demonstrated to partition to different parts of the cell. Herein, we investigated
      the role of lipid raft resident Src-family kinases (SFK) in stromal cell-derived
      factor 1/CXCL12-mediated chemotaxis. We have shown that Lck-deficient J.CaM 1.6
      cells are defective in CXCL12-mediated chemotaxis in contrast to their parental
      counterpart, Jurkat cells. Ectopic expression of the SFK hematopoietic cell
      kinase (Hck) in J.CaM 1.6 cells reconstituted CXCL12 responsiveness. The
      requirement of lipid raft association of SFK was assessed using both isoforms of
      Hck: the dually acylated p59(Hck) isoform that is targeted to lipid rafts and the
      monoacylated p61(Hck) isoform that is nonraft-associated. We have shown using
      several gain and loss of acylation alleles that dual acylation of Hck was
      required for CXCL12-mediated chemotaxis in J.CaM 1.6 cells. These results
      highlight the importance of the unique microenvironment provided by lipid rafts
      and their specific contribution in providing specificity to CXCL12 signaling.

PMID- 18632990
TI  - Human dendritic cell activities are modulated by the omega-3 fatty acid,
      docosahexaenoic acid, mainly through PPAR(gamma):RXR heterodimers: comparison
      with other polyunsaturated fatty acids.
AB  - There is accumulating evidence that omega-3 fatty acids may modulate immune
      responses. When monocytes were differentiated to dendritic cells (DCs) in the
      presence of docosahexaenoic acid (DHA), the expression of costimulatory and
      antigen presentation markers was altered in a concentration-dependent way,
      positively or negatively, depending on the markers tested and the maturation
      stage of the DCs. Changes induced by eicosapentaenoic acid and linoleic acid were
      similar but less intense than those of DHA, whereas oleic acid had almost no
      effect. DHA-treated, mature DCs showed inhibition of IL-6 expression and IL-10
      and IL-12 secretion, and their lymphoproliferative stimulation capacity was
      impaired. The phenotypic alterations of DCs induced by DHA were similar to those
      already reported for Rosiglitazone (Rosi), a peroxisome proliferator-activated
      receptor gamma (PPAR gamma) activator, and the retinoid 9-cis-retinoic acid
      (9cRA), a retinoid X receptor (RXR) activator. Moreover, DHA induced the
      expression of PPAR gamma target genes pyruvate dehydrogenase kinase-4 and aP-2 in
      immature DCs. The combination of DHA with Rosi or 9cRA produced additive effects.
      Furthermore, when DCs were cultured in the presence of a specific PPAR gamma
      inhibitor, all of the changes induced by DHA were blocked. Together, these
      results strongly suggest that the PPAR gamma:RXR heterodimer is the pathway
      component activated by DHA to induce its immunomodulatory effect on DCs.

PMID- 18632991
TI  - The pore region of N-methyl-D-aspartate receptors differentially influences
      stimulation and block by spermine.
AB  - The transmembrane and pore-forming regions of N-methyl-D-aspartate receptors
      containing the NR1 and NR2B subunits were studied by measuring the effects of
      various NR1 and NR2B mutants on stimulation and block by spermine. Block by
      spermine was predominantly affected by mutations in the M3 segment of NR1 and
      especially in the M1 and M3 segments of NR2B. These regions are in the outer
      vestibule of the channel pore and may contribute to a spermine binding site.
      Mutations in different regions-predominantly the M3 segment and M2 loop of NR1
      and the M3 segment of NR2B-influenced spermine stimulation, a surprising finding
      because spermine stimulation is thought to involve a spermine binding site in the
      distal, extracellular regulatory domain. However, some of these mutations also
      influence sensitivity to ifenprodil and protons, and changes in spermine
      sensitivity may be secondary to changes in proton sensitivity. The results are
      consistent with the proposal that the relative positions of the M1 and M3
      transmembrane segments and M2 loops are staggered or asymmetric in NR1 and NR2
      subunits, and with the idea that stimulation and block by spermine involve
      separate binding sites and distinct mechanisms, although some residues in the
      receptor subunits can affect both stimulation and block.

PMID- 18632992
TI  - Gap junction inhibitors reduce endothelium-dependent contractions in the aorta of
      spontaneously hypertensive rats.
AB  - Experiments were designed to determine the effect of gap junction inhibitors on
      endothelium-dependent contractions. Isolated aortic rings of spontaneously
      hypertensive rats (SHR) were suspended in vitro for isometric force recording.
      The nonselective gap junction inhibitor, carbenoxolone, reduced endothelium
      dependent contractions to acetylcholine and the calcium ionophore A23187 [5
      methylamino-2-(2S,3R,5R,8S,9S)-3,5,9-trimethyl-2-(1-oxo-(1H-pyrrol-2-yl)propan-2
      yl)-1,7-dioxaspiro-(5,5)undecan-8-yl)methyl)benzooxazole-4-carboxylic acid].
      There was no or modest effect of the gap peptides (40)Gap27, (37,43)Gap27, or
      (43)Gap26 when applied alone on endothelium-dependent contractions. However, the
      combined treatment with the three gap peptides significantly decreased
      endothelium-dependent contractions. The combined inhibition of the three
      connexins was not as effective as carbenoxolone, suggesting the involvement of
      other connexins in the process of endothelium-dependent contraction. The present
      study shows the involvement of gap junctions in endothelium-dependent
      contractions of the SHR aorta, presumably that of the combination of connexins
      37, 40, and 43 rather than a single subtype of these proteins. Contractions of
      the vascular smooth muscle caused by 9,11-dideoxy-11alpha, 9alpha
      epoxymethanoprostaglandin F(2alpha) (U46619) and prostacyclin, but not to those
      of endoperoxides and phenylephrine, were reduced only minimally by carbenoxolone.
      Thus, if gap junction signaling is involved in the contraction of the vascular
      smooth muscle to thromboxane-prostanoid receptor agonists, their contribution is
      small. This suggests that the reduction of endothelium-dependent contractions by
      carbenoxolone and the gap peptides cannot be attributed to the homocellular gap
      junctions between vascular smooth muscle, but is more likely to involve the
      homocellular gap junctions between endothelial cells and/or myoendothelial gap
      junctions.

PMID- 18632993
TI  - Telerehabilitation for service delivery in speech-language pathology.
AB  - Communication disorders in adults and children can have a significant effect on
      their quality of life and on that of their families. Speech-language pathologists
      face several challenges in providing assessment and treatment services to such
      people. Challenges include facilitating equitable access to services and
      providing appropriate management within a changing social and economic context.
      Telerehabilitation has the potential to deliver services in the home or local
      community via videoconferencing and through interactive computer-based therapy
      activities. This form of service delivery has the capacity to optimize functional
      outcomes by facilitating generalization of treatment effects within the person's
      everyday environment, and enable monitoring of communication and swallowing
      behaviours on a long-term basis. A number of image-based telerehabilitation
      applications have been used in the management of adult neurogenic speech and
      language disorders, stuttering, voice disorders, speech and language disorders in
      children, laryngectomy and swallowing dysfunction. Further development of such
      applications and other computer-based therapies, cost-benefit and cost
      effectiveness analyses, and professional education are needed if
      telerehabilitation is to become an integral part of speech-language pathology
      practice.

PMID- 18632994
TI  - Telehealth: a child and family-friendly approach to mental health-care reform.
AB  - Limited access to paediatric mental health services and high drop-out rates from
      treatment result in poor health outcomes for families with children with mental
      health problems. New ways of delivering care are required. Telehealth is a
      promising approach. The Family Help programme employs manualized, distance
      treatment by telephone. Participants in the Family Help programme (both adults
      and children) have reported a strong therapeutic alliance with their telephone
      coach. Participants also described how during treatment sessions they felt
      comfortable and safe in their own home; they did not feel stigmatized or judged;
      they had little apprehension about self-disclosure and they felt that treatment
      was delivered at their convenience. Treatment calls were often scheduled after
      typical working hours. Attrition rates were found to be very low and children
      actively engaged in the structured, distance treatment. Evidence-based, distance
      delivery using non-professionals is a promising approach to the delivery of
      paediatric mental health care.

PMID- 18632995
TI  - Effect of a behavioural health and specialty care telemedicine programme on goal
      attainment for youths in juvenile detention.
AB  - We conducted a pre-post study of the effect of a telepsychiatry counselling
      service on youths housed in three juvenile detention facilities. In the first
      year of the telemedicine programme, 321 psychiatry consultations were conducted
      via telemedicine; in the second year of the programme, 573 psychiatry
      consultations were conducted. Records for 190 students were then examined by two
      raters. The total number of behavioural goals for each adolescent increased from
      8.2 in the pre-telemedicine year to 8.7 in the first year of telemedicine and
      then to 10.0 in the second year (P < 0.05). In Year 2 of the study, subjects also
      had a significantly higher number of goals in four of the five categories:
      education, family, health and social skills (P < 0.05). Although other changes at
      the youth detention facilities or in the juvenile justice system may have been
      partly responsible for the effects observed, the study suggests that telemedicine
      may be useful for improving the rate of attainment of goals associated with
      family relations and personality/behaviour.

PMID- 18632996
TI  - Non-invasive monitoring of the activities of daily living of elderly people at
      home--a pilot study of the usage of domestic appliances.
AB  - We conducted a feasibility study of a system for non-invasive monitoring of
      subjects at home. Electrical activity was recorded from room lights and from
      electrical domestic appliances; this was translated into the probability of
      physical activity or a particular Activity of Daily Living (ADL). Thirteen
      volunteer subjects were monitored for a period of 6.4 months (range 3-8). The
      mean age of the subjects was 80 years and they all lived alone at home; one had
      moderate Alzheimer's disease. A one-week validation was carried out to ascertain
      whether the recorded activity actually occurred. The results showed that daily
      and nocturnal activity could be well differentiated. The probability of having
      eaten, taken a bath and going to the toilet could be calculated each day. Eating
      was the most accurately measured ADL; toileting and bathing results were less
      accurate. The system appears to be a promising component of home telecare.

PMID- 18632997
TI  - A paediatric therapeutic alliance occurs with distance intervention.
AB  - We investigated whether a distance therapeutic alliance occurs when children
      receive manualized, cognitive-behavioural treatment via telephone, in the absence
      of face-to-face contact. The therapeutic alliance scores were measured in 55
      child-parent pairs. The mean total Working Alliance Inventory child scores were
      236 (95% confidence interval [CI]: 232, 240) and the mean parent scores were 245
      (95% CI: 242, 247). Parent scores were significantly higher than child scores,
      although the difference may not be clinically meaningful. This study provides
      evidence that a strong therapeutic alliance does occur between child-coach and
      parent-coach pairs when treatment is delivered from a distance by non
      professionals. The term 'child' encompasses both children and adolescents.

PMID- 18632998
TI  - International telepsychiatry: a study of patient acceptability.
AB  - An international telepsychiatry service was established between Denmark and
      Sweden for cross-cultural patient groups, such as asylum seekers, refugees and
      migrants. Over an 18-month period starting in mid 2006, 30 patients were treated
      by telepsychiatry (21 men and 9 women). The patients received mental health care
      by videoconferencing from providers who spoke the patients' own language, i.e.
      without the assistance of interpreters. The total number of telepsychiatry
      sessions was 203 (range 1-22; average 6.8 sessions per patient). Patients
      completed a satisfaction questionnaire at the end of treatment. Seven patients
      (23%) were not able to complete a questionnaire, due to illiteracy and/or a
      psychotic condition. The rest of the patients (n=23) reported a high level of
      acceptance and satisfaction with telepsychiatry, as well as a willingness to use
      it again or recommend it to others. Any disadvantages of telemedicine were
      compensated by the fact that the doctor and patient spoke the same language and
      had similar cultural and/or national references. Mentally ill asylum seekers,
      refugees and migrants are under-served in their mother tongue and telepsychiatry
      can improve access to scarce health-care resources.

PMID- 18632999
TI  - The availability of telecardiology consultations and transfer patterns from a
      remote neonatal intensive care unit.
AB  - We examined records of all admissions to an isolated community neonatal intensive
      care unit (NICU) in California between 2001 and 2006. We also reviewed the
      echocardiograms for diagnosis, disposition of patient and necessity for
      transport. In 2004, a telemedicine link (mainly store-and-forward) was
      established to a university children's hospital (UCH) 290 km away. The number of
      NICU patients having an echocardiogram increased from 280 (27% of 1029
      admissions) to 385 (40% of 963, P = <0.001) after telemedicine became available.
      There was an increase in the proportion of normal studies, from 31% to 37% (P =
      0.03), and an increase in the number of patients diagnosed with cardiac pathology
      from 192 (19% of all admissions) to 241 (25%, P < 0.001). Twenty-four patients
      were transferred for cardiac reasons during each three-year period; however seven
      pre-telemedicine transfers were avoidable, compared with two post-telemedicine
      transfers (P = 0.06). There was a change in referral pattern (65% to the UCH pre
      telemedicine, compared with 78% post-telemedicine) although it was not
      significant (P = 0.10). Thus the availability of the telecardiology link was
      associated with increases in the utilization of echocardiography, in the
      proportion of normal studies, and in the percentage of neonates diagnosed with
      cardiac pathology without an increase in the number transferred for cardiac
      reasons. There was a reduction in unnecessary transfers and a strengthened
      relationship with the centre providing the telecardiology service.

PMID- 18633000
TI  - Feasibility of a home-based telerehabilitation system compared to usual care:
      arm/hand function in patients with stroke, traumatic brain injury and multiple
      sclerosis.
AB  - We conducted a randomized controlled multicentre trial to investigate the
      feasibility of a telerehabilitation intervention for arm/hand function (the Home
      Care Activity Desk [HCAD] training) in a home setting. Usual care was compared to
      HCAD training. The hypothesis was that the clinical outcomes of the HCAD
      intervention would be at least the same as those measured after a period of usual
      care for patients with stroke, traumatic brain injury (TBI) and multiple
      sclerosis (MS) with respect to their arm/hand function. Eighty-one patients with
      affected arm/hand function resulting from either stroke, MS or TBI were recruited
      in Italy, Spain and Belgium; 11 were lost during follow-up (14%). The outcome
      measures were the Action Research Arm Test (ARAT) and the Nine Hole Peg Test
      (NHPT). There were no significant differences between the two groups on the
      outcome measures (ARAT and NHPT); in both groups, patients maintained or even
      improved their arm/hand function. The HCAD training was found to be as feasible
      as usual care in terms of clinical outcomes, and both therapists and patients
      were satisfied with the HCAD intervention. A telerehabilitation intervention
      using HCAD may increase the efficiency of care.

PMID- 18633001
TI  - Satisfaction with care in post-stroke patients undergoing a telerehabilitation
      programme at home.
AB  - We conducted a pilot telerehabilitation study with post-stroke patients with arm
      motor impairment. We compared the degree of satisfaction of patients undergoing a
      virtual reality (VR) therapy programme at home (Tele-VR group) to satisfaction
      experienced by those undergoing the same VR therapy in a hospital setting (VR
      group). The rehabilitation equipment used a 3D motion tracking system to create a
      virtual environment in which the patient's movement was represented. In tele
      therapy, the patient equipment was installed in their homes, connected to the
      hospital by four ISDN lines at a total bandwidth of 512 kbit/s. Rehabilitation
      data were transmitted via one line and videoconferencing via the other three. Ten
      patients with mild to intermediate arm motor impairment due to an ischaemic
      stroke, were randomized into VR or Tele-VR groups. A questionnaire was used at
      the end of treatment to measure each patient's degree of satisfaction. Tele-VR
      treated patients showed median values equal to or higher than the VR group
      patients in all 12 items investigated, except one. In motor performance, the Tele
      VR group improved significantly (P < or = 0.05), while the VR group showed no
      significant change. Patients assigned to the Tele-VR group were able to engage in
      therapy at home and the videoconferencing system ensured a good relationship
      between the patient and the physical therapist whose physical proximity was not
      required.

PMID- 18633002
TI  - Caregivers' acceptance of electronic documentation in nursing homes.
AB  - A comparative study was conducted in two Australian nursing homes operated by the
      same organization. One home had implemented an electronic documentation system
      and the other remained paper-based. Survey questionnaires were answered by 14 of
      the 17 caregivers at the electronic documentation site (82%) and 10 of the 23
      caregivers at the paper documentation site (43%). They provided opinions about
      satisfaction with their home's documentation system, and the training and support
      provided. Information was also obtained on the caregivers' attitudes towards
      using electronic documentation. The caregivers at the electronic documentation
      site quickly adapted to the use of the new technology after receiving effective
      training and support. Caregivers at both homes were satisfied with their homes'
      documentation system, and had positive attitudes towards using electronic
      documentation systems. As an important communication tool, electronic nursing
      documentation may lead to improved efficacy of telemedicine in nursing home
      settings.

PMID- 18633003
TI  - The use of videoconferencing for mental health services in Finland.
AB  - The utilization of telemental health (TMH) services in Finland was surveyed in
      2006. In total, 135 health-care units provided responses. Eighty-four responses
      were received from primary care units (health-care centres and clinics) and eight
      from other clinics, in all hospital districts. The overall rate of TMH
      consultations was 4 per 100,000 population. The highest TMH consultation per
      population ratio, 22 per 100,000, was in northern Finland. Most of the sites used
      telepsychiatry services for less than 10% of clinical outpatient services. The
      sites with over 20% utilization of clinical TMH services from all psychiatric
      consultations were all rural health centres. Compared with Finland, the
      utilization rates of TMH were higher in Canada; that might be due to differences
      between the countries in the organization of mental health services in primary
      and specialized care. In Finland TMH consultations made up only a very small
      proportion of all mental health services. The use of TMH was particularly common
      in remote areas; however, there were many rural centres that did not utilize
      clinical TMH. TMH was widely utilized for continuing and medical education.

PMID- 18633004
TI  - Use of mobile phone cameras for after-hours triage in primary care.
AB  - Mobile phone images might be useful in after-hours triage of primary care. We
      conducted a study to identify population access to mobile phone cameras and to
      assess the clinical usefulness of mobile phone cameras. The survey was conducted
      among 480 patients attending two rural New Zealand practices. There were
      significantly more Maori owners compared to non-Maori (P = 0.002). Age was a
      significant factor influencing the ownership of mobile phones. We also conducted
      a clinical quiz among health professionals to assess how the provision of images
      on a mobile phone and on CD-ROM (to simulate the image that would be seen if
      email was used to transmit the images) influenced diagnostic confidence. Ten
      photographable clinical conditions were used to quiz 30 health professionals who
      were randomized into three groups of 10 each on diagnostic confidence. Images
      were found to significantly increase diagnostic confidence in all cases except
      one. It appears that mobile phone cameras are generally acceptable to patients
      and likely to be of practical use to rural practitioners in a range of clinical
      scenarios.

PMID- 18633005
TI  - We're tired of waiting.

PMID- 18633006
TI  - HIT happens: diagnosing and evaluating the patient with heparin-induced
      thrombocytopenia.

PMID- 18633007
TI  - Treatment of anaphylactic shock: where is the evidence?

PMID- 18633008
TI  - Progress is precarious.

PMID- 18633009
TI  - Does it add up?

PMID- 18633010
TI  - The incidence and implications of anti-heparin-platelet factor 4 antibody
      formation in a pediatric cardiac surgical population.
AB  - BACKGROUND: The incidence and implications of anti-heparin-platelet factor 4
      (PF4) antibody seroconversion in the pediatric cardiac surgical population remain
      largely unexplored. We sought to prospectively characterize the incidence of
      seroconversion in two populations: neonates undergoing primary cardiac surgery
      and children undergoing reoperative cardiac surgery with a history of
      unfractionated heparin (UFH) exposure. METHODS: One hundred and thirty-five
      consecutive patients were studied: Neonatal = 60 neonates, first time cardiac
      surgery. Reoperative (ReOp) = 75 children, reoperative cardiac surgery.
      Preoperative and postoperative day (POD) 5 and 10 blood samples were used to
      determine the presence of PF4 immunoglobulin (Ig)G, IgA, and IgM antibodies with
      enzyme-linked immunosorbent assay. RESULTS: No anti-heparin/PF4 antibodies were
      detected preoperatively in either group. On POD 5, antibodies were present in 1
      of 60 (1.7%) Neonatal; and in 12 of 75 (16%) ReOp; P = 0.006. On POD 10,
      antibodies were present in 1 of 60 (1.7%) Neonatal; and in 39 of 75 (52%) ReOp; P
      < 0.001. Seroconversion in ReOp patients on POD 10 was significantly associated
      (P = 0.03) with previous UFH exposures. Heparin-induced thrombocytopenia (HIT)
      was not diagnosed in any Neonatal patients. One ReOp patient (1.3%) seroconverted
      and developed HIT without thrombosis or skin lesions. CONCLUSIONS: HIT is a rare
      occurrence in pediatric cardiac surgical patients. The incidence of anti-heparin
      PF4 antibody seroconversion in children undergoing reoperation is approximately
      50% at 10 days postoperatively, a finding similar to that reported in adult
      cardiac surgical patients. Both age and previous UFH exposure correlate with this
      rate of seroconversion. In contrast, the rate of seroconversion in neonates
      undergoing first time surgery is substantially lower.

PMID- 18633011
TI  - Urgent cardiac surgery in a patient with a remote history of heparin-induced
      thrombocytopenia: use of the anti-PF4/heparin ELISA confirmatory test.
AB  - The use of established heparin protocols when heparin-induced thrombocytopenia
      (HIT) antibodies are negative is currently recommended for the management of
      patients with previous HIT who require cardiac surgery. Routine preoperative
      testing for HIT antibodies using an anti-PF4/heparin enzyme-linked immunosorbent
      assay (ELISA) introduces the problem of detecting nonpathogenic HIT antibodies,
      which can lead to a false diagnosis of the presence of platelet-activating
      antibodies. Our case report demonstrates the clinical utility of a newer
      confirmatory procedure performed using high dose heparin. We use this procedure
      in situations in which pretest probability is low (remote HIT) and the anti
      PF4/heparin ELISA test results are weak to moderately positive (absorbance 0.4
      1.0).

PMID- 18633012
TI  - The effects of hydroxyethyl starch 130/0.4 (6%) on blood loss and use of blood
      products in major surgery: a pooled analysis of randomized clinical trials.
AB  - BACKGROUND: The effects of different types of hydroxylethyl starch (HES) on blood
      coagulation closely depend on their physicochemical properties. HES with lower
      molar substitution and a lower in vivo molecular weight interferes relatively
      little with hemostasis and therefore results in lower perioperative blood losses
      and red blood cell (RBC) transfusion. To test this hypothesis, we analyzed pooled
      data from all available studies in major surgery comparing 6% HES 130/0.4 and 6%
      HES 200/0.5 from waxy maize starch. METHODS: Estimated blood loss, drainage loss,
      calculated blood loss, transfused blood product volumes, and coagulation
      variables were examined for 24 h after the start of surgery. Groups were compared
      using analysis of variance, evaluating several covariates. RESULTS: Four-hundred
      forty-nine patients from seven clinical trials were analyzed, 228 received HES
      130/0.4, and 221 received HES 200/0.5. For HES 130/0.4 patients, when compared to
      HES 200/0.5 patients, the estimated blood loss was reduced by 404 mL [P = 0.006],
      drainage loss was 272 mL less [P = 0.009], and calculated RBC loss was 149 mL
      less [P = 0.003]. RBC transfusion volumes were also lower for HES 130/0.4 by 137
      mL [P = 0.004]. In the early postoperative phase, HES 130/0.4 was found to exert
      significantly less effect on measures of coagulation, especially activated
      partial thromboplastin time and von Willebrand factor (antigen and ristocetin
      cofactor), than HES 200/0.5. CONCLUSIONS: Blood loss and transfusion requirements
      can be significantly reduced in major surgery when using third generation HES
      130/0.4 (Voluven) compared to second generation waxy maize starch HES 200/0.5.
      Since HES 130/0.4 and HES 200/0.5 were found similar regarding volume efficacy in
      other studies, HES 130/0.4 is recommended in this clinical setting.

PMID- 18633013
TI  - The influence of aprotinin and tranexamic acid on platelet function and
      postoperative blood loss in cardiac surgery.
AB  - BACKGROUND: Antifibrinolytic drugs including aprotinin and tranexamic acid are
      currently used in cardiac surgery to reduce postoperative bleeding and
      transfusion requirements, and may have different effects on platelets. We
      therefore evaluated platelet function after cardiopulmonary bypass (CPB) and
      cardiac surgery to determine the effect of either aprotinin or tranexamic acid.
      METHODS: In a prospective, randomized study, 50 patients scheduled for elective
      cardiac surgery with CPB were evaluated. Patients received high-dose aprotinin (n
      = 25) or tranexamic acid (n = 25) as antifibrinolytic drugs. Coagulation and
      platelet function were assessed preoperatively, after CPB, 3 and 24 h after
      surgery using modified thrombelastography and whole blood aggregometry. RESULTS:
      Impaired coagulation after CPB occurred in both groups compared with preoperative
      data (P < 0.01). In contrast to modified thrombelastography, thrombin receptor
      mediated aggregometry after CPB was significantly decreased only in those
      patients receiving tranexamic acid until the end of the study period in
      comparison to the aprotinin group (P < 0.05). Aprotinin-treated patients showed
      significantly less chest tube drainage (575 mL +/- 228 vs 1033 mL +/- 647, P <
      0.05) and need for postoperative transfusion requirements (P < 0.01) compared
      with the tranexamic acid group. CONCLUSIONS: Platelet function measured by whole
      blood aggregometry is better preserved by aprotinin than tranexamic acid and may
      be responsible for producing less bleeding within the first 24 h after CPB.

PMID- 18633014
TI  - Thrombelastography-guided factor VIIa therapy in a surgical patient with severe
      hemophilia and factor VIII inhibitor.
AB  - A patient with hemophilia and factor VIII inhibitors required urgent evacuation
      of a spinal cord hematoma. Two large doses of recombinant factor VIIa (200
      microg/kg followed by 300 microg/kg) were required for hemostasis. Traditional
      and rotational thrombelastography were used to guide dose and timing of rFVIIa
      therapy. With the limitations of prothrombin and partial thromboplastin times as
      perioperative monitors of rFVIIa efficacy, this description of thrombelastography
      supports reports of in vitro use, and may be helpful when large perioperative
      doses of rFVIIa are required.

PMID- 18633015
TI  - Thromboelastography-guided recombinant factor VIIa administration in a patient
      with refractory autoimmune idiopathic thrombocytopenia.
AB  - Autoimmune idiopathic thrombocytopenia poses a significant challenge for
      clinicians in the perioperative period. Repeat platelet transfusions may not
      result in satisfactory increments in the platelet count and routine coagulation
      screens may not reflect the degree of abnormal hemostasis. We report the use of
      point-of-care testing with thromboelastography and platelet counting in managing
      a patient with refractory autoimmune idiopathic thrombocytopenia, undergoing a
      splenectomy for active bleeding. These tests were successfully used to monitor
      the frequency of administration of recombinant factor VIIa (NovoSeven(R),
      NovoNordisk, Copenhagen, Denmark) with platelet transfusions.

PMID- 18633016
TI  - Anaphylactic reaction after systemic application of aprotinin triggered by
      aprotinin-containing fibrin sealant.
AB  - We report a 67-yr-old male after multiple surgical procedures for treatment of
      arterial occlusive disease who suffered an anaphylactic reaction after
      administration of aprotinin (Trasylol) prior to urgent coronary artery bypass
      surgery. The patient had been treated with aprotinin-containing fibrin sealant in
      2004 and in 2007, 2 wk before coronary artery bypass surgery. The postoperative
      serologic screening revealed positive results for qualitative aprotinin-specific
      IgG, highly elevated quantitative aprotinin-specific IgG and moderately elevated
      aprotinin-specific IgE antibodies.

PMID- 18633017
TI  - Catecholamine-induced cardiomyopathy and pheochromocytoma.

PMID- 18633018
TI  - Factors predictive of poor behavioral compliance during inhaled induction in
      children.
AB  - BACKGROUND: Preoperative identification of children at risk of emotional distress
      and poor behavioral compliance during inhaled induction of anesthesia allows
      targeted interventions to reduce distress, thereby enhancing the quality of the
      anesthetic experience. We sought to identify patient, procedural, and health care
      system factors predictive of poor behavioral compliance during induction.
      METHODS: We studied 861 developmentally appropriate children ages 1-13 yr, The
      American Society of Anesthesiologists physical status I to III, presenting for
      inhaled induction of anesthesia. All inductions were performed in an induction
      room with parent(s) present. Behavioral compliance was assessed using the
      Induction Compliance Checklist (ICC), an observational scale consisting of 10
      behaviors scored as the number of behaviors observed during induction; ICC > or
      =4 was considered poor behavioral compliance. A multivariable ordinal logistic
      regression model for behavioral compliance was generated and the performance of
      the multivariable model was evaluated by the c statistic. RESULTS: Twenty-one
      percent of children exhibited poor behavioral compliance on induction. Factors
      increasing the odds of poor behavioral compliance were younger age (< 4 yr, P <
      0.0001), shorter preoperative preparation time (P = 0.004), and high anxiety
      levels in the preoperative clinic (modified-Yale preoperative anxiety scale > 40;
      P = 0.016). Previous anesthesia experience increased the odds in school-age
      children (P = 0.046); this effect was ameliorated in children attending the
      preoperative tour (P = 0.018). The model using these factors demonstrated
      moderate discrimination between children with poor compliance and those with
      perfect compliance (ICC = 0) (c statistic = 0.75). CONCLUSIONS: Factors
      predictive of poor behavioral compliance were age, previous anesthesia,
      preoperative tour attendance, preoperative preparation time and anxiety levels in
      the preoperative clinic. These factors, bundled into a predictive algorithm, may
      help identify children who could benefit from behavioral or pharmacological
      interventions and avoid use of interventions to those at low risk.

PMID- 18633019
TI  - Pediatric mastocytosis: routine anesthetic management for a complex disease.
AB  - BACKGROUND: Pediatric mastocytosis consists of a spectrum of clinical variants
      characterized by increased numbers of resident mast cells in various organ
      systems. Mast cells are instrumental in mediating anaphylaxis and patients with
      mastocytosis are at risk to develop provoked and unprovoked episodes of
      anaphylaxis. METHODS: We examined perianesthetic records of patients with
      pediatric mastocytosis who were anesthetized for diagnostic and surgical
      procedures from 1993 to 2006. In addition, we conducted a literature review of
      the anesthetic experience in pediatric mastocytosis. RESULTS: Twenty-two patients
      with pediatric mastocytosis, with a median age of 3.2 yr (range, 6 mo-20 yr) at
      the time of the procedure, were anesthetized for 29 diagnostic and surgical
      procedures. All variants of the disease are represented in this series. Most
      patients had a history of flushing, pruritus, gastro-esophageal reflux diseases,
      and abdominal pain; one patient had a history of spontaneous anaphylaxis. Routine
      anesthetic techniques were used and, despite the complexity of the disease, the
      perioperative courses were uncomplicated and without serious adverse events.
      CONCLUSIONS: We reviewed the main features of pediatric mastocytosis, its
      anesthetic and perioperative implications, and describe a practical approach to
      the anesthetic management of pediatric patients with the disease. Although many
      drugs used routinely in anesthesia reportedly caused mast cell degranulation,
      deviations from routine anesthesia techniques are not necessarily warranted.
      However, an understanding of the anesthetic implications of the disease and
      meticulous preparation to treat possible adverse events are advised.

PMID- 18633020
TI  - Antiemetic prophylaxis for postdischarge nausea and vomiting and impact on
      functional quality of living during recovery in patients with high emetic risks:
      a prospective, randomized, double-blind comparison of two prophylactic antiemetic
      regimens.
AB  - BACKGROUND: We compared two antiemetic prophylaxis regimens, their efficacy for
      preventing postdischarge nausea and vomiting, and their impact on quality of
      living, during recovery. METHODS: Sixty-four women undergoing outpatient
      gynecological surgery and at high risk for emesis were randomized into one of two
      groups. The study group received intraoperative IV dexamethasone 8 mg and
      ondansetron 4 mg, followed with an 8 mg oral disintegrating ondansetron tablet,
      to be taken on discharge and in the morning of postoperative days 1 and 2. The
      control group received only the IV ondansetron 4 mg intraoperatively. The
      incidence and severity of emetic symptoms and pain were assessed while patients
      were in the recovery room and via telephone and patient diary for 5 days after
      discharge. A modified functional living index of emesis was used to assess the
      impact on quality of living during recovery. RESULTS: Sixty patients, 30 in each
      group, completed the study. The incidences for postdischarge nausea were 57% and
      20%, and for postdischarge vomiting 20% and 3% in the control and study groups,
      respectively, for the period between the 8th and 120th hours postanesthesia (P <
      0.05). Thirty-three percent of the study and 60% of the control group reported
      that emetic symptoms negatively affected their quality of living (P < 0.05).
      CONCLUSIONS: When compared with a single dose of intraoperative IV ondansetron
      prophylaxis, our study regimen of additional intraoperative dexamethasone and
      once a day ondansetron significantly reduced the incidence of postdischarge
      nausea and vomiting and its negative impact on quality of living during the first
      5 days of recovery.

PMID- 18633021
TI  - A randomized, double-blind study to evaluate the efficacy and safety of three
      different doses of palonosetron versus placebo in preventing postoperative nausea
      and vomiting over a 72-hour period.
AB  - BACKGROUND: We designed this multicenter, randomized, double-blind study to
      assess the efficacy and safety of three doses of palonosetron, compared with
      placebo, on the incidence and severity of postoperative nausea and vomiting
      (PONV) in inpatients for 72 h after surgery. METHODS: Female patients undergoing
      either elective gynecological or breast surgery were stratified according to two
      additional PONV risk factors: nonsmoking status and history of PONV and/or motion
      sickness. Five hundred forty-four patients with one or both of these risk factors
      were randomized to receive one of the three doses of IV palonosetron (0.025 mg,
      0.050 mg, 0.075 mg) or placebo immediately before induction of anesthesia. The
      primary efficacy end-point was complete response (CR: no emesis and no use of
      rescue medications) evaluated at the 0-24 and 24-72 h time intervals after
      surgery. RESULTS: CR rates for placebo and palonosetron 0.075 mg were 36% and 56%
      for 0-24 h (P = 0.001), 52% and 70% for 24-72 h (P = 0.002) and 36% and 52% (P =
      0.010) for the 0-72 h postoperative interval. Palonosetron 0.075 mg was
      associated with less intense nausea (e.g., toward "mild" or "none") versus
      placebo during the 0-24 h (P < 0.001) time interval and significantly delayed
      median time to emesis (P = 0.002) and treatment failure (P = 0.004). Although CR
      rates for both the 0.025 mg and 0.050 mg palonosetron doses were not
      statistically superior to placebo for the 0-24 h or 24-72 h periods, both lower
      doses reduced nausea severity during the 0-24 h period (P = 0.040 and P = 0.004).
      CONCLUSION: A single 0.075-mg IV dose of palonosetron effectively reduced the
      severity of nausea and delayed the time to emesis and treatment failure in the
      inpatient surgical setting; lower doses were not as effective.

PMID- 18633022
TI  - A randomized, double-blind study to evaluate the efficacy and safety of three
      different doses of palonosetron versus placebo for preventing postoperative
      nausea and vomiting.
AB  - BACKGROUND: In this randomized, double-blind study we assessed the efficacy and
      safety of three different doses of the 5-HT(3) receptor antagonist palonosetron,
      compared with placebo, on the incidence and severity of postoperative nausea and
      vomiting (PONV) for 72 h postsurgery. METHODS: Five hundred seventy-four patients
      undergoing either outpatient abdominal or gynecological laparoscopic surgery were
      stratified according to gender, history of PONV or motion sickness, and
      nonsmoking status. Patients with > or =2 PONV risk factors were eligible and
      randomized to receive one of three doses of IV palonosetron (0.025 mg, 0.050 mg,
      or 0.075 mg) or placebo immediately prior to induction of anesthesia. Co-primary
      efficacy end-points included complete response (CR: no emetic episodes and no
      rescue medication) during the 0 to 24 h and 24 to 72 h postoperative time
      intervals. RESULTS: A dose-response trend in the proportion of patients with a CR
      was observed with increasing doses of palonosetron in the first 24 hrs. CR rates
      for placebo and palonosetron 0.075 mg were 26% and 43%, respectively, for the 0
      to 24 h postoperative interval (P = 0.004), and 41% and 49%, respectively, for
      the 24 to 72 h interval (P = 0.188). Compared with placebo, palonosetron 0.075 mg
      was associated with a significant downward shift toward less intense nausea (P =
      0.042) and with significant reduction in the impact of PONV on patient
      functioning (P = 0.004) during the 0 to 24 h interval. CONCLUSIONS: A single
      0.075-mg IV dose of palonosetron significantly increased the CR rate (no emetic
      episodes and no rescue medication) from 0 to 24 h, decreased nausea severity and
      patients experienced significantly less interference in their postoperative
      function due to PONV.

PMID- 18633023
TI  - The impact of current antiemetic practices on patient outcomes: a prospective
      study on high-risk patients.
AB  - BACKGROUND: In this prospective, multicenter, observational study, we evaluated
      the incidence and time course of postoperative nausea and vomiting (PONV),
      assessed prophylactic and rescue antiemetic use in high-risk patients, and
      determined population-based effectiveness of antiemetics, including the impact of
      American Society of Anesthesiologists (ASA) and American Society of
      Perianesthesia Nurses (ASPAN) guideline compliance. METHODS: Eligible patients
      undergoing elective laparoscopic or major plastic surgery possessed two or more
      of the following Apfel PONV risk factors: female gender, history of PONV or
      motion sickness, and nonsmoking status. Antiemetic use, emetic episodes, severity
      of nausea, and functional interference due to PONV were documented during the
      first 72 h after surgery. Complete response (CR) was defined as no emesis or
      rescue medication use, and complete control was defined as CR and no moderate
      severe nausea. The effect of compliance (versus noncompliance) with ASA and ASPAN
      guidelines on PONV outcomes was also analyzed. RESULTS: The proportion of
      patients experiencing postoperative emesis ranged from 18% to 40% depending on
      the number of antiemetics administered. The rate of rescue medication (45%) was
      similar to the reported incidences of moderate-to-severe nausea (47%) and
      functional interference due to emetic symptoms (44%). The administration of three
      or more antiemetics produced better patient outcomes overall compared to <1
      prophylactic antiemetic. CR rates were <70% despite adherence to current
      organizational PONV management guidelines (ASA: 69%; ASPAN: 63%). The complete
      control rates were 10% lower than CR rates over the 3 day study period.
      CONCLUSIONS: Administration of three or more prophylactic antiemetics had the
      most positive impact on emetic outcomes over 72 hrs in patients at risk of
      developing PONV. Although compliance with organizational PONV management
      guidelines improved patient outcomes, postoperative emetic symptoms and
      interference with patient functioning still occurred in more than 30% of these
      high-risk patients.

PMID- 18633024
TI  - The relationship between patient risk factors and early versus late postoperative
      emetic symptoms.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) remain common complications
      after elective surgery. Prophylactic antiemetic drugs are frequently administered
      to patients with well known risk factors for developing PONV. We designed this
      prospective observational study to assess the relationship between common patient
      risk factors for developing PONV and the occurrence of early (0-24 h) versus late
      (24-72 h) emetic symptoms. METHODS: One hundred thirty patients undergoing
      elective laparoscopic (n = 88) or plastic (n = 42) surgery were assigned a risk
      score for developing PONV based on the Apfel risk scoring system, which assigns
      one point each for female gender, nonsmoking status, history of PONV or motion
      sickness, and postoperative opioid use. It was assumed that all patients would
      receive an opioid analgesic in the postoperative period. The patients received 0,
      1, 2, or 3 antiemetic drugs for prophylaxis. The occurrence of nausea, vomiting,
      and need for rescue antiemetics was assessed at specific time intervals from 0 to
      6, 6-24, and 24-72 h after surgery. In addition, the impact of PONV on recovery
      of normal activities of daily living was assessed using a standardized patient
      questionnaire. RESULTS: One or more prophylactic antiemetics were administered to
      87%, 90%, and 95% of the patients in the two, three, and four Apfel risk-factor
      groups, respectively. In the presence of three or four risk factors, >/=2
      antiemetics were administered to 56% and 75% of the patients, respectively.
      Vomiting was reported in 11% and 22% of patients in the three and four risk
      factor groups compared with 6% in the two risk factor group at 0-6 h, and 13% and
      27% (vs 0%) at 6-24 h, respectively. However, in the 24-72 h postoperative
      period, the incidences of emesis were low and did not differ in the three risk
      groups (9%, 5%, and 11%, respectively). The occurrence of moderate-to-severe
      nausea was increased in the higher risk groups at 0-6 h and 6-24 h (19%-28% vs 6%
      and 20%-30% vs 9%, respectively). However, the incidences of nausea in the 24-72
      h period in the three and four risk factor groups were not different from the two
      risk factor group (5% and 8% vs 6%, respectively). The need for rescue
      antiemetics and interference of emetic symptoms with normal activities was
      greater in the four risk factor group compared with the two and three risk factor
      groups. CONCLUSION: Despite the frequent use of multiple antiemetic drugs for
      prophylaxis, an Apfel risk score of three or four (vs 2) was associated with a
      higher incidence of emetic sequelae in the first 24 h after surgery. However, the
      occurrence of late (24-72 h) emetic symptoms was low and appeared to be unrelated
      to the patient's Apfel risk score.

PMID- 18633025
TI  - Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor.
AB  - BACKGROUND: Palonosetron is a 5-HT(3)-receptor antagonist (5-HT(3)-RA) that has
      been shown to be superior to other 5-HT(3)-RAs in phase III clinical trials for
      the prevention of acute, delayed, and overall chemotherapy-induced nausea and
      vomiting. The improved clinical efficacy of palonosetron may be due, in part, to
      its more potent binding and longer half-life. However, these attributes alone are
      not sufficient to explain the results with palonosetron. We sought to elucidate
      additional differences among 5-HT(3)-RAs that could help explain the observations
      in the clinic. METHODS: Receptor site saturation binding experiments were
      performed with [3H] palonosetron, [3H] granisetron, and [3H] ondansetron to
      obtain the corresponding Scatchard analyses and Hill coefficients. Diagnostic
      equilibrium binding experiments and kinetic dissociation experiments were
      conducted to examine competitive versus potential allosteric interactions between
      ondansetron, granisetron and palonosetron and the 5-HT(3) receptor. Finally, the
      long-term effect of the three antagonists on receptor function as measured by
      Ca2+ influx in HEK 293 cells expressing the 5-HT(3)-receptor was compared.
      RESULTS: Analyses of binding isotherms using both Scatchard and Hill plots
      suggested positive cooperativity for palonosetron and simple bimolecular binding
      for both granisetron and ondansetron. Equilibrium diagnostic tests discriminated
      differential effects of palonosetron on [3H] ligand binding indicating that
      palonosetron was an allosteric antagonist whereas granisetron and ondansetron
      were competitive antagonists. Using dissociation rate strategies, palonosetron
      was shown to be an allosteric modifier that accelerated the rate of dissociation
      from the receptor of both granisetron and ondansetron. Differences in the binding
      mode of palonosetron to the 5-HT(3) receptor were shown to have an impact on
      receptor function. In these experiments, cells were incubated with each
      antagonist, followed by infinite dilutions and dissociation for 2.5 h; cells
      previously incubated with either granisetron or ondansetron showed calcium-ion
      influx similar to control cells that had not been exposed to a 5-HT(3) receptor
      antagonist. In contrast, substantial inhibition of calcium-ion influx was
      observed in cells that had been incubated with palonosetron. CONCLUSIONS:
      Palonosetron exhibited allosteric binding and positive cooperativity when binding
      to the 5-HT(3) receptor. Palonosetron also triggered functional effects that
      persisted beyond its binding to the 5-HT(3) receptor at the cell surface.
      Differences in binding and effects on receptor function may be relevant to the
      unique beneficial actions of palonosetron. To our knowledge, this is the first
      report showing palonosetron's interaction with the 5-HT(3) receptor at the
      molecular level, clearly differentiating it from other 5-HT(3)-RAs.

PMID- 18633026
TI  - Inhaled anesthetics do not combine to produce synergistic effects regarding
      minimum alveolar anesthetic concentration in rats.
AB  - BACKGROUND: We hypothesized that pairs of inhaled anesthetics having divergent
      potencies [one acting weakly at minimum alveolar anesthetic concentration (MAC);
      one acting strongly at MAC] on specific receptors/channels might act
      synergistically, and that such deviations from additivity would support the
      notion that anesthetics act on multiple sites to produce anesthesia. METHODS:
      Accordingly, we studied the additivity of MAC for 11 anesthetic pairs divergently
      (one weakly, one strongly) affecting a specific receptor/channel at MAC. By
      "divergently," we usually meant that at MAC the more strongly acting anesthetic
      enhanced or blocked the in vitro receptor or channel at least twice (and usually
      more) as much as did the weakly acting anesthetic. The receptors/channels
      included: TREK-1 and TASK-3 potassium channels; and gamma-aminobutyric acid type
      A, glycine, N-methyl-D-aspartic acid, and acetylcholine receptors. We also
      studied the additivity of cyclopropane-benzene because the N-methyl-D-aspartic
      acid blocker MK-801 had divergent effects on the MACs of these anesthetics. We
      also studied four pairs that included nitrous oxide because nitrous oxide had
      been reported to produce infraadditivity (antagonism) when combined with
      isoflurane. RESULTS: All combinations produced a result within 10% of that which
      would be predicted by additivity except for the combination of isoflurane with
      nitrous oxide where infraadditivity was found. CONCLUSIONS: Such results are
      consistent with the notion that inhaled anesthetics act on a single site to
      produce immobility in the face of noxious stimulation.

PMID- 18633028
TI  - Is synergy the rule? A review of anesthetic interactions producing hypnosis and
      immobility.
AB  - BACKGROUND: Drug interactions may reveal mechanisms of drug action: additive
      interactions suggest a common site of action, and synergistic interactions
      suggest different sites of action. We applied this reasoning in a review of
      published data on anesthetic drug interactions for the end-points of hypnosis and
      immobility. METHODS: We searched Medline for all manuscripts listing propofol,
      etomidate, methohexital, thiopental, midazolam, diazepam, ketamine,
      dexmedetomidine, clonidine, morphine, fentanyl, sufentanil, alfentanil,
      remifentanil, droperidol, metoclopramide, lidocaine, halothane, enflurane,
      isoflurane, sevoflurane, desflurane, N2O, and Xe that contained terms suggesting
      interaction: interaction, additive, additivity, synergy, synergism, synergistic,
      antagonism, antagonistic, isobologram, or isobolographic. When available, data
      were reanalyzed using fraction analysis or response surface analysis. RESULTS:
      Between drug classes, most interactions were synergistic. The major exception was
      ketamine, which typically interacted in either an additive or infra-additive
      (antagonistic) manner. Inhaled anesthetics typically showed synergy with IV
      anesthetics, but were additive or, in the case of nitrous oxide and isoflurane,
      possibly infra-additive, with each other. CONCLUSIONS: Except for ketamine, IV
      anesthetics acting at different sites usually demonstrated synergy. Inhaled
      anesthetics usually demonstrated synergy with IV anesthetics, but no pair of
      inhaled anesthetics interacted synergistically.

PMID- 18633027
TI  - General anesthetics have additive actions on three ligand gated ion channels.
AB  - BACKGROUND: The purpose of this study was to determine whether pairs of
      compounds, including general anesthetics, could simultaneously modulate receptor
      function in a synergistic manner, thus demonstrating the existence of multiple
      intraprotein anesthetic binding sites. METHODS: Using standard electrophysiologic
      methods, we measured the effects of at least one combination of benzene,
      isoflurane (ISO), halothane (HAL), chloroform, flunitrazepam, zinc, and
      pentobarbital on at least one of the following ligand gated ion channels: N
      methyl-D-aspartate receptors, glycine receptors and gamma-aminobutyric acid type
      A receptors. RESULTS: All drug-drug-receptor combinations were found to exhibit
      additive, not synergistic modulation. ISO with benzene additively depressed N
      methyl-D-aspartate receptors function. ISO with HAL additively enhanced glycine
      receptors function, as did ISO with zinc. ISO with HAL additively enhanced gamma
      aminobutyric acid type A receptors function as did all of the following: HAL with
      chloroform, pentobarbital with ISO, and flunitrazepam with ISO. CONCLUSION: The
      simultaneous allosteric modulation of ligand gated ion channels by general
      anesthetics is entirely additive. Where pairs of general anesthetic drugs
      interact synergistically to produce general anesthesia, they must do so on
      systems more complex than a single receptor.

PMID- 18633029
TI  - Additivity versus synergy: a theoretical analysis of implications for anesthetic
      mechanisms.
AB  - BACKGROUND: Inhaled anesthetics have been postulated to act at multiple
      receptors, with modest action at each site summing to produce immobility to
      noxious stimulation. Recent experimental results affirm prior findings that
      inhaled anesthetics interact additively. Synergy implies multiple sites of action
      by definition. In this essay, we explore the converse: does additivity imply a
      single site of action? METHODS: The interaction of one versus two ligands
      competing for the same binding site at a receptor was explored using the law of
      mass action. Circuits were then constructed to investigate how the potency of
      drugs and the steepness of the concentration versus response relationship is
      amplified by the arrangement of suppressors into serial circuits, and enhancers
      into parallel circuits. Assemblies of suppressor and enhancer circuits into
      signal processing units were then explored to investigate the constraints signal
      processing units impose on additive interactions. Lastly, the relationship
      between synergy, additivity, and fractional receptor occupancy was explored to
      understand the constraints imposed by additivity. RESULTS: Drugs that compete for
      a single receptor, and that similarly affect the receptor, must be additive in
      their effects. Receptors that bind suppressors in serial circuits, or enhancers
      in parallel circuits, increase the apparent potency of the drugs and the
      steepness of the concentration versus response relationship. When assemblies of
      suppressor and enhancer circuits are arranged into signal processing units, the
      interactions may be additive or synergistic. The primary determinant is the
      relationship between the concentration of drug associated with the effect of
      interest and the concentration associated with 50% receptor occupancy, k(d).
      Effects mediated by very low concentrations are more likely to be additive.
      Similarly, inhaled anesthetics that act at separate sites are unlikely to exhibit
      additive interactions if anesthetic drug effect occurs at concentrations at or
      above 50% receptor occupancy. However, if anesthetic drug effect occurs at very
      low levels of receptor occupancy, then additivity is expected even among
      anesthetics acting on different receptors. CONCLUSIONS: Additivity among drugs
      acting on different receptors is only likely if the concentrations responsible
      for the drug effect of interest are well below the concentration associated with
      50% receptor occupancy.

PMID- 18633030
TI  - Synergy between pairs of competitive antagonists at adult human muscle
      acetylcholine receptors.
AB  - BACKGROUND: Synergistic neuromuscular blocking effects have been observed
      clinically with certain pairs of nicotinic acetylcholine receptor (nAChR)
      competitive antagonists. The mechanism for synergy has not been elucidated. We
      tested the hypothesis that synergy arises from a differential selectivity of
      antagonists for the two ligand binding sites on adult human nAChR. METHODS: We
      expressed nAChR in BOSC23 cells. We applied ACh with or without antagonists to
      outside-out patches and measured macroscopic currents at room temperature. We
      determined the IC(90) for (+)-tubocurarine, metocurine, pancuronium, vecuronium,
      cisatracurium, rocuronium, and atracurium. For 15 combinations of two
      antagonists, we determined the IC(90) for one antagonist in the presence of the
      IC(70) of a second antagonist. We constructed isobolograms for 90% inhibition.
      For single antagonists, we measured inhibition of receptors containing mutations
      in the epsilon- and delta-subunits to determine site selectivity. RESULTS: Two
      pairs of antagonists, metocurine+cisatracurium and cisatracurium+ atracurium
      exhibited additive inhibition. Ten combinations, including (+)-tubocurarine+
      pancuronium and pancuronium+vecuronium, were highly synergistic such that the
      combination was two to three times more effective than expected for additivity.
      Three combinations were 1.5-1.6 times more effective than expected for
      additivity. Inhibition by (+)-tubocurarine and metocurine was sensitive to
      mutations in the epsilon-subunit only. Vecuronium was affected by the delta
      subunit mutation only. Inhibition by other antagonists was decreased by mutations
      in either subunit. CONCLUSIONS: Many combinations of antagonists exhibited
      synergistic effects on adult human nAChR. Synergy was observed with structurally
      similar and dissimilar antagonists. The degree of synergy did not always
      correlate well with site specificity assayed with mutants. In some, but not all
      cases, the synergy at the receptor level correlated with clinical determinations
      of synergy. We conclude that the synergistic actions of muscle relaxants can be
      partially explained by direct interactions with adult human nAChR.

PMID- 18633031
TI  - Propofol protects hepatic L02 cells from hydrogen peroxide-induced apoptosis via
      activation of extracellular signal-regulated kinases pathway.
AB  - BACKGROUND: Propofol protects cells against ischemia/reperfusion injury in
      several organs, but there are few reports of its effect on liver epithelial
      cells. We investigated the effect of propofol preconditioning on human hepatic
      L02 cells under hydrogen peroxide (H2O2)-induced oxidative stress and attempted
      to determine whether the extracellular signal-regulated kinases (ERK) pathway is
      involved in this process. METHODS: Preconditioned or nonpreconditioned human
      hepatic L02 cells were exposed to H2O2 and the changes of apoptosis were
      evaluated by TUNEL assay, Caspase-3 and poly ADP-ribose polymerase (PARP)
      cleavage. Activation of ERK1/2 and mitogen-activated protein kinase//ERK Kinase
      1/2 (MEK1/2) was measured by Western blot analysis. The mRNA expression of Bcl-2,
      Bcl-x(L), Bad, and Bax was quantified by real-time quantitative reverse
      transcriptase polymerase chain reaction. RESULTS: Propofol preconditioning
      reduced the population of apoptotic cells and Caspase-3 and PARP cleavage induced
      by H2O2 inhepatic L02 cells. L02 cells treated with propofol (0.01-0.3 mM) alone,
      led to a dose-dependent activation of ERK and MEK, and such activation was
      detected within 0.5 h and eventually declined to <50% at 4 h. The addition of the
      specific inhibitor PD98059 completely abolished the activation of ERK and
      aggravated the extent of apoptosis. Moreover, propofol treatment repressed the
      mRNA expression of proapoptotic genes Bad and Bax, and this repression could be
      partly reversed by PD98059. CONCLUSIONS: These findings demonstrate that propofol
      protects hepatic L02 cells from H2O2-induced apoptosis, partly through activating
      the MEK-ERK pathway and further suppressing Bad and Bax expression.

PMID- 18633032
TI  - The performance of six pulse oximeters in the environment of neuronavigation.
AB  - BACKGROUND: Although the use of pulse oximeters may be regarded a standard of
      care for monitoring anesthesia procedures, these monitors may be susceptible to
      various kinds of disturbances. Recently, it was suggested that neuronavigation
      equipment may interfere with pulse oximeter accuracy. In this study, we evaluated
      the effect of a neurosurgical image guidance system on the performance of six
      different pulse oximeters. Two simple shielding methods were evaluated. METHODS:
      Twenty healthy, adult, nonsmoking volunteers were equipped with six different
      pulse oximeters on both hands. Baseline values for heart rate, arterial oxygen
      saturation, and signal quality were assessed. After activation of the Brain Lab
      VectorVision Neuronavigation System, the effects on signal quality and saturation
      recognition were evaluated. Measurements were repeated using two different
      shielding techniques, a cotton blanket and aluminum sheets. RESULTS: Activation
      of the image guidance system resulted in a significant disturbance of signal
      quality and saturation detection, which was partially reversible by both
      shielding techniques. Significant differences were noted among the six brands of
      pulse oximeters for signal quality (P < 0.001) and saturation recognition (P <
      0.001), and for the response to shielding methods (P < 0.001). Coverage of the
      probes with aluminum foil resulted an in undisturbed saturation recognition in
      all subjects with almost all monitors. CONCLUSIONS: Infrared pulse waves from
      neurosurgical navigation equipment may interfere with pulse oximeter
      measurements. Shielding the probe with aluminum foil sufficiently eliminated the
      infrared interference.

PMID- 18633033
TI  - The effects of auditory evoked potential click sounds on bispectral index and
      entropy.
AB  - BACKGROUND: The click sounds of auditory evoked potentials (AEP) might have some
      effect on electroencephalogram indices and Bispectral Index (BIS) but many
      studies, unconcerned about this effect, have measured both indices
      simultaneously. In this study, I examined the effects, of AEP click sounds on the
      BIS, and also on the response entropy (RE) and state entropy (SE) of the entropy
      monitor. METHODS: Forty patients aged 40-70 yr and scheduled for surgery of lower
      extremities under spinal anesthesia were anesthetized with 0.5% bupivacaine or
      tetracaine. Patients were sedated with midazolam 1 mg followed by propofol
      infusion started at 1 mg.kg(-1).h(-1). Propofol infusion was controlled to keep
      BIS or SE at 80, 60, or 40 for several minutes, and then click sounds (65 dB) of
      the AEP were given for 60 s. The changes in BIS, RE, and SE were observed
      continuously for 60 s after the click sounds had stopped. RESULTS: BIS, SE, and
      RE significantly increased during the click sounds. The longest duration of
      increase was at BIS or SE 60. CONCLUSION: AEP monitor click sounds transiently
      increased the simultaneously measured BIS, RE, and SE during different levels of
      sedation by propofol infusion during spinal anesthesia. Therefore, the effects of
      the click sounds should be considered when these monitors are used simultaneously
      in the same patient.

PMID- 18633034
TI  - An evaluation of gas humidifying devices as a means of intraperitoneal local
      anesthetic administration for laparoscopic surgery.
AB  - BACKGROUND: Intraperitoneal local anesthetic administration has been reported to
      provide perioperative analgesia during laparoscopic procedures. The aim of this
      in vitro study was to assess the efficiency of commercially available
      humidification devices to deliver ropivacaine and to determine the effects of
      modifying the device's position between the insufflator and the Veress needle on
      the amount of ropivacaine delivered. METHODS: In the first experiment, four
      humidification devices filled with ropivacaine (0.20% and 0.75%) were placed at
      the outlet of a laparoscopic insufflation system delivering a constant carbon
      dioxide flow. A catheter was connected to the humidifier's outlet and the other
      end submerged in a calibrated vial containing 25 mL of 50% methanol in water. The
      concentration of ropivacaine collected in the methanol-water solution was
      measured using high performance liquid chromatography. In the second experiment,
      the clinical situation was imitated by placing 3 m of silicone tubing between the
      humidifier and the collection vial to evaluate its influence on the amount of
      ropivacaine delivered. Only one humidifier was tested in the second experiment
      because the other three tested humidification devices did not efficiently deliver
      ropivacaine. RESULTS: The evaporation-based humidifiers delivered very small or
      nonmeasurable quantities of ropivacaine. In contrast, the microvibration-based
      aerosol humidification device delivered significant amounts (89.1%-94.3%) of the
      drug. The insertion of silicone tubing between the humidifier and the collecting
      vial reduced the amount of delivered ropivacaine to 62.3%. CONCLUSIONS: The
      microvibration-based aerosol humidification device may be used to deliver local
      anesthetics during laparoscopic procedures. Further research is necessary to
      confirm these results in clinical practice and to provide effective
      humidification that does not blur the surgeon's view.

PMID- 18633035
TI  - Coronary artery stents: Part I. Evolution of percutaneous coronary intervention.
AB  - The subspecialty of interventional cardiology has made significant progress in
      the management of coronary artery disease over the past three decades with the
      development of percutaneous coronary transluminal angioplasty, atherectomy, and
      bare-metal and drug-eluting stents (DES). Bare-metal stents (BMS) maintain vessel
      lumen diameter by acting as a scaffold and prevent collapse incurred by
      angioplasty. However, these devices cause neointimal hyperplasia leading to in
      stent restenosis and requiring reintervention in more than 20% of patients by 6
      mo. DES (sirolimus and paclitaxel) prevent restenosis by inhibiting neointimal
      hyperplasia. However, DESs also delay endothelialization, causing the stents to
      remain thrombogenic for an extended, yet unknown, period of time. Late stent
      thrombosis is associated with a 45% mortality rate. Premature discontinuation of
      antiplatelet therapy, particularly clopidogrel, is the strongest predictor of
      stent thrombosis. Sixty percent of patients receive stents for off-label
      (unapproved) indications, which also increases the frequency of stent thrombosis.
      Clopidogrel and aspirin are the cornerstone of therapy in the prevention of stent
      thrombosis in both BMS and DES. Recommendations pertaining to the optimal
      duration of dual-antiplatelet therapy have been debated. Both the Food and Drug
      Administration and the American Heart Association/American College of
      Cardiologists, in association with other major societies, have made
      recommendations to extend the duration of dual-antiplatelet therapy in patients
      with DES to 1 yr. The 6-wk duration of dual-antiplatelet therapy in patients with
      BMS remains unchanged. All patients with coronary stents must remain on life-long
      aspirin monotherapy. Since the introduction of percutaneous transluminal coronary
      angioplasty for the treatment of coronary atherosclerosis, the practice of
      percutaneous coronary intervention has undergone a dramatic transformation from
      simple balloon dilation catheters to sophisticated mechanical endoprostheses.
      These advancements have impacted the practice of perioperative medicine. In this
      series of two articles, in Part I we will review the evolution of percutaneous
      coronary intervention and discuss the issues associated with percutaneous
      transluminal coronary angioplasty and coronary stenting; in Part II we will
      discuss perioperative issues and management strategies of coronary stents during
      noncardiac surgery.

PMID- 18633036
TI  - Coronary artery stents: II. Perioperative considerations and management.
AB  - The management of patients with coronary artery stents during the perioperative
      period is one of the most important patient safety issues clinicians confront.
      Perioperative stent thrombosis is a life-threatening complication for patients
      with either bare-metal or drug-eluting stents. Noncardiac surgery appears to
      increase the risk of stent thrombosis, myocardial infarction, and death,
      particularly when patients undergo surgery early after stent implantation. The
      incidence of complications is further increased when dual-antiplatelet therapy is
      discontinued preoperatively. It is generally agreed that aspirin must be
      continued throughout the perioperative period, except in circumstances when the
      risk of bleeding significantly outweighs the benefit of continued
      anticoagulation, such as procedures performed in a closed space. We present
      considerations for regional anesthesia, as well as postoperative recommendations
      as the occurrence of perioperative stent thrombosis appears to be greatest during
      this period. Immediate percutaneous coronary intervention is the definitive
      treatment for perioperative stent thrombosis, and 24-h access to an
      interventional cardiology suite should be readily available. Algorithms for
      perioperative management of patients with bare-metal and drug-eluting stents are
      proposed.

PMID- 18633037
TI  - Life after death: the aftermath of perioperative catastrophes.
AB  - Most anesthesiologists will experience the perioperative death of a patient or a
      major perioperative catastrophe in the course of their careers. Anesthesia
      training, however, does not prepare individuals to handle the aftermath of such a
      stressful event. Multiple surveys have shown that the death of a patient has a
      major emotional impact on up to 75% of health care providers involved, regardless
      of whether the death was expected or whether the patient was well known to the
      practitioner. Psychological recovery often takes weeks or months and is hampered
      by lack of emotional and professional support. Data indicate that the majority of
      anesthesiologists would prefer a more formal support structure, including the
      option to take time off from clinical work. Although a formal assessment of
      professional functioning after a perioperative catastrophe has not been done, the
      Association of Anaesthetists of Great Britain and Ireland instituted guidelines
      recommending support at multiple levels, and the "Adverse Event Protocol"
      available on the Anesthesia Patient Safety Foundation website provides a
      suggested series of steps to minimize patient injury and identify the cause of an
      adverse anesthesia event after it occurs. The negative consequences of failure to
      cope well after these events are significant to individuals and health care
      systems alike. Further study into the short-term and long-term impact of
      perioperative catastrophes on providers and health systems is needed.
      Additionally, education on how to handle the aftermath of perioperative
      catastrophes and formal support structures should be provided to practitioners at
      all levels of training.

PMID- 18633038
TI  - Failed tracheal intubation with the LMA-CTrach in two patients with lingual
      tonsil hyperplasia.
AB  - The LMA-CTrach combines the features of the Intubating Laryngeal Mask Airway with
      a fiberoptic system and a screen for visualization of the airway. Local
      pathology, such as lingual tonsillar hyperplasia, may obstruct the view of the
      airway leading to unanticipated difficult intubation. We present two cases of
      failed intubation with the LMA-CTrach in patients with lingual tonsillar
      hyperplasia. In both cases, the LMA-CTrach maintained adequate ventilation,
      giving time to prepare alternative strategies.

PMID- 18633039
TI  - Intubation bougie dissection of tracheal mucosa and intratracheal airway
      obstruction.
AB  - Intubation bougies are commonly used to aid in intubation when an optimal view of
      the larynx is not obtained. We describe a case of tracheal perforation using a
      disposable intubation bougie resulting in a complete intratracheal airway
      obstruction relieved by cricothyrotomy. Disposable intubation bougies may have
      mechanical properties that differ from their nondisposable counterparts making
      complications more likely.

PMID- 18633040
TI  - The intrathoracic blood volume index as an indicator of fluid responsiveness in
      critically ill patients with acute circulatory failure: a comparison with central
      venous pressure.
AB  - BACKGROUND: The intrathoracic blood volume index (ITBVI) and central venous
      pressure (CVP) are routinely used to predict fluid responsiveness in critically
      ill patients with acute circulatory failure (systolic blood pressure < 90 mm Hg
      or vasopressor requirement). However, they have never been compared. METHODS: In
      this prospective interventional study, we included 35 (21 men) mechanically
      ventilated and sedated patients with acute cardiovascular failure requiring
      cardiac output measurement (transpulmonary thermodilution technique). Fluid
      responsiveness was defined as an increase in stroke index (cardiac output/heart
      rate/body surface area) > or =15%. Receiver operating characteristic curves were
      generated for ITBVI and CVP. RESULTS: Fluid challenge induced a stroke index
      increase > or =15% in 18 (51%) patients (responders). At baseline, no studied
      hemodynamic variables were different between responders and nonresponders. The
      areas under the receiver operating characteristic curves were 0.64 [95% CI: 0.46
      0.80] for ITBVI and 0.68 [95% CI: 0.50-0.83] for CVP, without any statistical
      difference (P = 0.73). The best cut-off values for CVP and ITBVI were 9 mm Hg
      (sensitivity = 61%; specificity = 82%) and 928 mL . m(-2) (sensitivity = 78%;
      specificity = 53%). CONCLUSION: ITBVI is similar to CVP in its ability to predict
      fluid responsiveness in critically ill patients with acute circulatory failure.

PMID- 18633041
TI  - Pulmonary effects of noninvasive ventilation combined with the recruitment
      maneuver after cardiac surgery.
AB  - BACKGROUND: The aim of our study was to evaluate the pulmonary effects of
      noninvasive ventilation (NIV) with or without recruitment maneuver (RM) after
      open heart surgery. METHODS: One-hundred patients undergoing coronary artery
      bypass surgery were randomized into four groups after the operation: 1) RM with
      sustained inflation during mechanical ventilation postoperatively (RM group, n =
      25); 2) RM combined with NIV applied for 1/2-h periods every 6 h in the first
      postoperative day after tracheal extubation (RM-NIV group, n = 25); 3) NIV after
      tracheal extubation (NIV group, n = 25); and 4) a control group consisting of
      patients receiving neither RM nor NIV (control group, n = 25). Pulmonary function
      tests, oxygenation index, and atelectasis on chest radiograph were evaluated and
      compared among the groups. RESULTS: RM provided higher arterial oxygen levels
      during mechanical ventilation and after tracheal extubation compared to other
      interventions. Oxygenation was better in the RM-NIV and NIV groups than in the
      control group (P = 0.02 and P = 0.008, respectively) at the end of the study. The
      postoperative atelectasis score of the control group (median: 1) was higher than
      those of the RM (1; P = 0.03), RM-NIV (0; P < 0.01) and NIV (0; P < 0.01) groups.
      Pulmonary function of the NIV groups on postoperative day 2 was better than in
      the other groups, whereas the tests were similar among the groups on
      postoperative day 7. CONCLUSIONS: NIV associated with RM provided better
      oxygenation both during and after the mechanical ventilation period. NIV either
      alone or in combination with RM provided lower atelectasis scores and better
      early pulmonary function tests compared to the control group, without a
      significant difference regarding the duration of mechanical ventilation,
      intensive care unit stay, and the length of hospitalization. NIV combined with RM
      is recommended after open heart surgery to prevent postoperative atelectasis and
      hypoxemia.

PMID- 18633042
TI  - The pivotal role of vasopressin in refractory anaphylactic shock.
AB  - BACKGROUND: Severe anaphylaxis can be associated with cardiovascular collapse
      that is difficult to manage and does not respond to treatment with epinephrine.
      Because anaphylaxis is uncommon, unpredictable and may be fatal, a prospective,
      randomized, controlled trial in humans on the best management is difficult and
      guidelines are based on theory and anecdotes only. METHODS AND RESULTS: We report
      six cases in which the use of vasopressin was successful in the treatment of
      anaphylactic shock. CONCLUSIONS: Standard treatment of anaphylactic shock,
      including discontinuation of the causative agent, administration of epinephrine,
      and infusion of IV fluids, did not stabilize cardiocirculatory function, and
      adding arginine vasopressors resulted in prompt hemodynamic stabilization.

PMID- 18633043
TI  - A randomized controlled trial of pudendal nerve block for pain relief after
      episiotomy.
AB  - BACKGROUND: Pain from episiotomy or perineal tears during childbirth is
      associated with significant pain in the postpartum period. We performed this
      randomized, double-blind, controlled trial to investigate the efficacy of nerve
      stimulator-guided unilateral pudendal nerve block for pain relief after
      episiotomy. METHODS: Forty women who gave birth vaginally with mediolateral
      episiotomy were randomized to receive pudendal nerve block with 15 mL of either
      ropivacaine 7.5 mg/mL (pudendal group) or normal saline (control group) after
      repair of the episiotomy. Episiotomy pain was assessed with a visual analog scale
      at rest at 3, 6, 12, 24, and 48 h postepisiotomy and during activities (walking
      and sitting). Breakthrough pain (visual analog scale >30 mm) was treated with
      niflumic acid suppositories 700 mg every 12 h. The primary outcome variables were
      pain scores at rest and during activities over 48 h postpartum. RESULTS:
      Demographic and obstetric characteristics were not different between groups.
      Successful pudendal nerve stimulation was achieved in all patients. Patients in
      the pudendal group reported significantly lower pain scores at rest than those in
      the control group at 3, 6, 12, 24, and 48 h after delivery (P < 0.05). They also
      reported better analgesia while sitting and walking (P < 0.05). Additional
      analgesia was required by three patients (15%) in the pudendal group versus 17
      patients (85%) in the placebo group (P < 0.001). CONCLUSION: This study
      demonstrates that nerve stimulator-guided unilateral pudendal nerve block with
      ropivacaine 7.5 mg/mL is associated with decreased pain and need for additional
      analgesics during the first 48 h postepisiotomy.

PMID- 18633044
TI  - Random drug testing to reduce the incidence of addiction in anesthesia residents:
      preliminary results from one program.
AB  - Substance abuse occurs in approximately 1%-2% of anesthesia residents and nearly
      80% of programs have had one or more resident (s) with such a problem. Education
      and control efforts have failed to reduce the frequency of substance abuse.
      Anesthesia providers have a professional obligation to be drug-free for the well
      being of their patients. We have instituted a program of preplacement and random
      urine testing of residents in anesthesiology in an attempt to decrease the
      incidence of substance abuse. We demonstrate that such a program is feasible,
      despite logistic and cultural obstacles. Larger multi-institutional studies will
      be required to determine whether instituting a program of random urine testing
      decreases the incidence of substance abuse in anesthesiology residents.

PMID- 18633045
TI  - A study of cognitive dysfunction in patients having carotid endarterectomy
      performed with regional anesthesia.
AB  - BACKGROUND: In previous studies, we found that approximately 25% of patients
      having carotid endarterectomy with general anesthesia (CEA general) develop
      cognitive dysfunction compared with a surgical control Group 1 day and 1 mo after
      surgery. In this study, we tested the hypothesis that patients having CEA with
      regional anesthesia (CEA regional) will develop significant cognitive dysfunction
      1 day after surgery compared with a control group of patients receiving sedation
      1 day after surgery. We did not study persistence of dysfunction. METHODS: To
      test this hypothesis, we enrolled 60 patients in a prospective study. CEA
      regional was performed with superficial and deep cervical plexus blocks in 41
      patients. The control group consisted of 19 patients having coronary angiography
      or coronary artery stenting performed with sedation. A control group is necessary
      to account for the "practice effect" associated with repeated cognitive testing.
      The patients from the CEA regional group were enrolled at New York Medical Center
      and the control group at Columbia-Presbyterian Medical Center. The cognitive
      performance of all patients was evaluated using a previously validated battery of
      neuropsychometric tests. Differences in performance, 1 day after compared with
      before surgery, were evaluated by both event-rate and group-rate analyses.
      RESULTS: On postoperative day 1, 24.4% of patients undergoing CEA regional had
      significant cognitive dysfunction, where "significant" was defined as a total
      deficit score > or =2 SD worse than the mean performance in the control group.
      CONCLUSIONS: Patients undergoing CEA regional had an incidence of cognitive
      dysfunction which was not different than patients having CEA general as
      previously published and compared with a contemporaneously enrolled group.

PMID- 18633046
TI  - Intravenous dexmedetomidine decreases lung permeability induced by intracranial
      hypertension in rats.
AB  - BACKGROUND: Intracisternal dexmedetomidine (Dex) attenuates cardiac dysfunction
      in rats with intracranial hypertension (ICH). However, the effects of IV Dex on
      cardiac function and lung permeability during ICH have not been evaluated. We
      tested the hypothesis that IV Dex attenuates hemodynamic changes and decreases
      lung permeability induced by ICH in rats. METHODS: Halothane-anesthetized and
      mechanically ventilated rats were divided into four groups. In two groups, a
      subdural balloon catheter was inflated for 60 s to produce ICH. Arterial blood
      gas analysis was performed before and 30 min after ICH. Mean arterial blood
      pressure, heart rate (HR) and intracranial pressure were monitored for 30 min.
      The Dex group (n = 8) received IV Dex 80 microg/kg, followed by 6 microg.kg(
      1).min(-1) (40 microg/mL) for 10 min and the control group (n = 8) received IV
      saline 2 mL/kg, followed by at 0.15 mL.kg(-1).min(-1) for 10 min. Surgery was
      performed without ICH with Dex (Sham-Dex group, n = 5) and without Dex (Sham
      control, n = 5). In all groups, pulmonary permeability was measured using a
      modification of the Evans blue dye extravasation technique. IV Evans blue dye 20
      mg/kg was administered 2 h before being killed and Evans blue dye in plasma and
      lung tissue was quantified by dual-wavelength spectrophotometric analysis.
      RESULTS: There were no significant differences in basal arterial blood pressure,
      HR, and Pao(2) among groups. In the control group, ICH resulted in transient
      increases in mean arterial blood pressure and HR, followed by a rapid decline and
      a plateau. In the Dex group, mean arterial blood pressure showed a transient
      increase and subsequent, rapid decrease to baseline, whereas HR did not change
      during ICH. Pao2 was higher in the Dex group than in the control group after ICH
      [138 (127-169) vs 78 (59-124) mm Hg, median (range), P < 0.01]. The pulmonary
      permeability index was lower in the Dex group than the control group [430 (182
      450) vs 570 (427-1170), P < 0.01]. It was however, higher in the Sham-Dex group
      than the Sham-Control group [25 (24-35) vs 6 (4-7), P < 0.01]. CONCLUSIONS:
      Prophylactic IV Dex decreases lung permeability as well as hemodynamic changes
      induced by ICH in rats.

PMID- 18633047
TI  - Anesthetic management of a patient with 3-methylcrotonyl-CoA carboxylase
      deficiency.
AB  - Patients with inborn errors of metabolism require special considerations in
      perioperative care. In the following case report, we describe the successful
      management of a patient with 3-methylcrotonyl-CoA carboxylase deficiency, a
      deficit that causes a secondary carnitine deficiency and impaired beta oxidation.
      Patients may have significant underlying cardiomyopathy, and are at risk for
      metabolic decompensation, acidosis, and hypoglycemia during periods of stress.

PMID- 18633048
TI  - A multiple-day regimen of parecoxib sodium 20 mg twice daily provides pain relief
      after total hip arthroplasty.
AB  - BACKGROUND: This multicenter, multiple-dose, randomized, double-blind, parallel
      group study compared the analgesic efficacy and safety of two dosing regimens of
      parecoxib sodium (parecoxib) versus placebo after total hip arthroplasty.
      METHODS: On study Day 1, 490 patients received a postoperative initial loading
      dose of IV parecoxib 40 mg, followed by a re-dose of parecoxib 20 mg in 484 of
      490 patients. Subsequently, 479 randomized patients received double-blind
      treatment with parecoxib 20 mg bid (n = 159), parecoxib 20 mg qd (n = 159)
      followed by placebo, or placebo (n = 161) on Day 2. RESULTS: Patients treated
      with parecoxib 20 mg bid reported significantly lower summed pain intensity over
      24 h (SPI-24) scores and improved patients' global evaluation of study medication
      (PGESM) ratings compared with placebo-treated patients on Days 2 to 5 (P < 0.05).
      For patients treated with parecoxib 20 mg qd, SPI-24 scores were significantly
      lower on Days 3 and 4 (P < 0.05), and PGESM ratings significantly improved on Day
      5 compared with placebo. The incidence of adverse events was similar in all
      treatment groups with the exception of fever, vomiting and impaired
      concentration, which were significantly more common in the placebo group compared
      with one or other of the parecoxib treatment groups (P < 0.05). CONCLUSION:
      Multiple-day administration of parecoxib 20 mg once or twice daily is effective
      and generally well tolerated after total hip arthroplasty.

PMID- 18633049
TI  - The effect of acupressure at the extra 1 point on subjective and autonomic
      responses to needle insertion.
AB  - BACKGROUND: Premedication with sedatives can decrease the discomfort associated
      with invasive anesthetic procedures. Some researchers have shown that acupressure
      on the acupuncture extra 1 point is effective for sedation. We investigated
      whether acupressure on the extra 1 point could alleviate the pain of needle
      insertion. METHODS: We investigated the effect of acupressure at the extra 1
      point or a sham point on needle insertion using verbal rating scale (VRS) pain
      scores and heart rate variability (HRV). Twenty-two healthy female volunteers
      were randomly allocated to two groups: the extra 1 group received acupressure at
      the extra 1 point, and the sham group received acupressure at a sham point. After
      starting the electrocardiogram record, a 27-gauge needle was inserted into the
      skin of a forearm. Thereafter, another needle was inserted into the skin of the
      other forearm during acupressure. RESULTS: Acupressure at the extra 1 point
      significantly reduced the VRS, but acupressure at the sham increased the VRS.
      Acupressure at the extra 1 significantly reduced the low frequency/high frequency
      ratio of HRV responding to needle insertion. CONCLUSIONS: Acupressure at the
      extra 1 point significantly reduced needle insertion pain compared with
      acupressure at the sham point. Also, acupressure at the extra 1 point
      significantly reduced the low frequency/high frequency ratio of HRV responding to
      needle insertion, which implies a reduction in sympathetic nervous system
      activity.

PMID- 18633050
TI  - The feasibility of patient-controlled paravertebral analgesia for major breast
      cancer surgery: a prospective, randomized, double-blind comparison of two
      regimens.
AB  - BACKGROUND: Paravertebral analgesia is useful for breast surgery. Patient
      controlled analgesia by IV or epidural routes is well established for delivering
      postoperative analgesia. Our objective was to apply patient control to
      paravertebral analgesia and evaluate the efficacy and tolerability of two
      distinct dosing regimens. METHODS: Patients undergoing major breast cancer
      surgery were recruited for this prospective, double-blind, randomized trial of
      two patient-controlled paravertebral analgesia regimens: 19 patients received
      levobupivacaine 0.2% at 8 mL/h with 3-mL bolus and 15-min lockout (15-min lockout
      group); 18 received levobupivacaine 0.2% at 4 mL/h with 8-mL bolus and 30-min
      lockout (30-min lockout group). Our primary outcome was dynamic pain scores
      (visual analog scale) at 4-hourly intervals for 36 h. Secondary outcomes were
      resting pain scores, rescue analgesia requirements, volume of levobupivacaine
      administered, demands for levobupivacaine, levobupivacaine boluses received, and
      patient satisfaction. RESULTS: Resting and dynamic pain scores were comparable in
      the groups. Two 15-min lockout patients and five 30-min lockout patients required
      rescue analgesia (P = 0.23). Patients received 400 +/- 95 mL and 330 +/- 130 mL
      levobupivacaine in 15-min and 30-min lockout groups, respectively (P = 0.012).
      The 15-min lockout group requested a bolus 75 +/- 16 times; the 30-min lockout
      group requested it 69 +/- 14 times (P = 0.40). However, the 15-min lockout group
      received 39 +/- 22 boluses and the 30-min lockout group only 24 +/- 16 (P =
      0.02). Systolic pressure, heart rate, respiratory rate, sedation scores, nausea,
      antiemetic requirement, and satisfaction scores were similar in each group.
      CONCLUSIONS: Patient-controlled paravertebral analgesia for breast cancer
      surgery, with either regimen, provided satisfactory analgesia and was well
      tolerated.

PMID- 18633051
TI  - A dose-ranging study of intraarticular midazolam for pain relief after knee
      arthroscopy.
AB  - BACKGROUND: A variety of analgesic techniques have been used to manage
      postoperative pain after arthroscopic knee surgery. Intraarticular midazolam may
      have an analgesic effect similar to that seen when midazolam is used in a
      centroneuraxial fashion. METHODS: Sixty ASA status I or II patients undergoing
      knee arthroscopy with general anesthesia were randomized to receive
      intraarticular midazolam 50 mug/kg, 75 mug/kg, or isotonic saline. We assessed
      the efficacy of the analgesic technique with visual analog scale pain scores,
      time until first request for analgesics, and cumulative analgesic consumption.
      Patients were observed for 48 h. RESULTS: The addition of intraarticular
      midazolam significantly reduced visual analog pain scores in the early
      postoperative period compared with saline. Both doses similarly prolonged
      duration until first request for analgesic compared with saline (4.7 and 4.6 vs
      0.7 h). There was no statistically significant difference between the two doses
      of midazolam or cumulative 48 h analgesic consumption. CONCLUSIONS: We conclude
      that when intraarticular midazolam was compared with placebo there was a
      reduction in pain after day-case arthroscopic knee surgery; however, this pain
      relief was of relatively short duration.

PMID- 18633053
TI  - Prolonged use of high-dose morphine impairs angiogenesis and mobilization of
      endothelial progenitor cells in mice.
AB  - BACKGROUND: Morphine is one of the most commonly prescribed analgesics for
      treating wound pain. Using a mouse model of excisional wound injury, we
      determined the effects of high-dose morphine on angiogenesis and mobilization of
      endothelial progenitor cells. METHODS: An excisional wound was created on mice
      treated with placebo or morphine (20 mg/kg, i.p. injection for 14 days). Wound
      healing was compared by measuring the final-to-initial wound area ratio.
      Generation of superoxide anions in the wound was determined by luminol-enhanced
      chemiluminescence. Circulating mononuclear cells were isolated and measured for
      endothelial progenitor cell (defined as CD34+/CD133+ cell) counts. In vivo and in
      vitro measurements of angiogenesis after morphine treatment were performed using
      the Matrigel assay. RESULTS: Mice treated with morphine had reduced wound closure
      and higher wound superoxide ions concentrations than control mice. Morphine
      reduced the number of postwound circulating endothelial progenitor cells.
      Matrigel assay showed impaired angiogenesis in animals and reduced capillary tube
      formation in cultured endothelial cells treated with morphine. CONCLUSION: High
      dose morphine impaired angiogenesis, increased systemic oxidative stress, and
      impaired mobilization of endothelial progenitor cells. This study emphasizes the
      potential detrimental effect of high-dose morphine on angiogenesis after systemic
      administration.

PMID- 18633052
TI  - Modulators of calcium influx regulate membrane excitability in rat dorsal root
      ganglion neurons.
AB  - BACKGROUND: Chronic neuropathic pain resulting from neuronal damage remains
      difficult to treat, in part, because of incomplete understanding of underlying
      cellular mechanisms. We have previously shown that inward Ca2+ flux (I(Ca))
      across the sensory neuron plasmalemma is decreased in a rodent model of chronic
      neuropathic pain, but the direct consequence of this loss of I(Ca) on function of
      the sensory neuron has not been defined. We therefore examined the extent to
      which altered membrane properties after nerve injury, especially increased
      excitability that may contribute to chronic pain, are attributable to diminished
      Ca2+ entry. METHODS: Intracellular microelectrode measurements were obtained from
      A-type neurons of dorsal root ganglia excised from uninjured rats. Recording
      conditions were varied to suppress or promote I(Ca) while biophysical variables
      and excitability were determined. RESULTS: Both lowered external bath Ca2+
      concentration and blockade of I(Ca) with bath cadmium diminished the duration and
      area of the after-hyperpolarization (AHP), accompanied by decreased current
      threshold for action potential (AP) initiation and increased repetitive firing
      during sustained depolarization. Reciprocally, elevated bath Ca2+ increased the
      AHP and suppressed repetitive firing. Voltage sag during neuronal
      hyperpolarization, indicative of the cation-nonselective H-current, diminished
      with decreased bath Ca2+, cadmium application, or chelation of intracellular
      Ca2+. Additional recordings with selective blockers of I(Ca) subtypes showed that
      N-, P/Q, L-, and R-type currents each contribute to generation of the AHP and
      that blockade of any of these, and the T-type current, slows the AP upstroke,
      prolongs the AP duration, and (except for L-type current) decreases the current
      threshold for AP initiation. CONCLUSIONS: Taken together, our findings show that
      suppression of I(Ca) decreases the AHP, reduces the hyperpolarization-induced
      voltage sag, and increases excitability in sensory neurons, replicating changes
      that follow peripheral nerve trauma. This suggests that the loss of I(Ca)
      previously demonstrated in injured sensory neurons contributes to their
      dysfunction and hyperexcitability, and may lead to neuropathic pain.

PMID- 18633054
TI  - Intrathecal clonidine suppresses phosphorylation of the N-methyl-D-aspartate
      receptor NR1 subunit in spinal dorsal horn neurons of rats with neuropathic pain.
AB  - BACKGROUND: Intrathecal (IT) administration of the alpha-2 adrenoceptor agonist,
      clonidine, produces significant analgesic effects. Although several mechanisms
      underlying clonidine-induced analgesia have been proposed, the possible
      interaction with N-methyl-D-aspartate (NMDA) receptors as a major antinociceptive
      mechanism has not been addressed. We designed the present study to determine
      whether clonidine or other analgesics can affect spinal NMDA receptor activation
      in rats with chronic constriction injury (CCI)-induced neuropathy. METHODS: Rats
      underwent unilateral CCI, and received IT clonidine (1, 5, 20 microg/rat), [D
      Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO, mu opioid receptor agonist, 1
      microg/rat), gabapentin (anticonvulsant, 100 microg/rat) or vehicle 2 wks later.
      After drug injection, we measured the pain response to thermal or mechanical
      stimuli and used immunohistochemistry to evaluate spinal cord phosphorylated NMDA
      receptor subunit 1 (pNR1) expression. RESULTS: Two weeks after CCI surgery, rats
      displayed significant mechanical allodynia and thermal hyperalgesia, and the
      spinal cord dorsal horn showed a significant increase in the number of pNR1
      immunoreactive neurons. IT injection of clonidine (20 microg/rat), DAMGO and
      gabapentin potently reduced mechanical allodynia and thermal hyperalgesia.
      Importantly, IT clonidine, but not IT DAMGO or gabapentin, dose-dependently
      reduced CCI-induced pNR1 expression in all lamina of the spinal cord dorsal horn
      by 30 min after injection. In addition, IT injection of the alpha-2 adrenoceptor
      antagonist, idazoxan (40 microg/rat) 10 min before clonidine injection completely
      reversed clonidine's antihyperalgesic and antiallodynic effects, as well as
      clonidine's suppressive effect on CCI-induced NR1 phosphorylation in the spinal
      cord dorsal horn. CONCLUSIONS: Our data indicate that IT clonidine's
      antihyperalgesic/antiallodynic effect on neuropathic pain is associated with a
      significant reduction in spinal NMDA receptor phosphorylation and suggests a
      potentially novel mechanism of clonidine's action.

PMID- 18633056
TI  - Factors affecting the distribution of neural blockade by local anesthetics in
      epidural anesthesia and a comparison of lumbar versus thoracic epidural
      anesthesia.
AB  - The spread of sensory blockade after epidural injection of a specific dose of
      local anesthetic (LA) differs considerably among individuals, and the factors
      affecting this distribution remain the subject of debate. Based on the results of
      recent investigations regarding the distribution of epidural neural blockade,
      specifically for thoracic epidural anesthesia, we noted that the total mass of LA
      appears to be the most important factor in determining the extent of sensory,
      sympathetic, and motor neural blockade, whereas the site of epidural
      needle/catheter placement governs the pattern of distribution of blockade
      relative to the injection site. Age may be positively correlated with the spread
      of sensory blockade, and the evidence is somewhat stronger for thoracic than for
      lumbar epidural anesthesia. Other patient characteristics and technical details,
      such as patient position, and mode and speed of injection, exert only a small
      effect on the distribution of sensory blockade, or their effects are equivocal.
      However, combinations of several patient and technical factors may aid in
      predicting LA dose requirements. Based on these results, we have also formulated
      suggested epidural insertion sites that may optimize both analgesia and
      sympathicolysis for various surgical indications.

PMID- 18633055
TI  - The effects of varying local anesthetic concentration and volume on continuous
      popliteal sciatic nerve blocks: a dual-center, randomized, controlled study.
AB  - BACKGROUND: It remains unknown whether local anesthetic concentration, or simply
      total drug dose, is the primary determinant of continuous peripheral nerve block
      effects. We therefore tested the null hypothesis that providing different
      concentrations and rates of ropivacaine, but at equal total doses, produces
      comparable effects when used in a continuous sciatic nerve block in the popliteal
      fossa. METHODS: Preoperatively, a perineural catheter was inserted adjacent to
      the sciatic nerve using a posterior popliteal approach in patients undergoing
      moderately painful orthopedic surgery at or distal to the ankle. Postoperatively,
      patients were randomly assigned to receive a perineural ropivacaine infusion of
      either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through
      the second postoperative day. Therefore, both groups received 16 mg of
      ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient
      controlled bolus dose. The primary end point was the incidence of an insensate
      limb, considered undesirable, during the 24-h period beginning the morning after
      surgery. Secondary end points included analgesia and patient satisfaction.
      RESULTS: Patients given 0.2% ropivacaine (n = 25) experienced an insensate limb
      with a mean (sd) of 1.8 (1.8) times, compared with 0.6 (1.1) times for subjects
      receiving 0.4% ropivacaine (n = 25; estimated difference = 1.2 episodes, 95%
      confidence interval, 0.3-2.0 episodes; P = 0.009). In contrast, analgesia and
      satisfaction were similar in each group. CONCLUSIONS: For continuous popliteal
      sciatic nerve blocks, local anesthetic concentration and volume influence block
      characteristics. Insensate limbs were far more common with larger volumes of
      relatively dilute ropivacaine. During continuous sciatic nerve block in the
      popliteal fossa, a relatively concentrated solution in smaller volume thus
      appears preferable.

PMID- 18633057
TI  - Valid and relevant outcome measures are critical for objective hypothesis
      testing.

PMID- 18633058
TI  - Dr. Paul: views through the piperidine ring.

PMID- 18633059
TI  - Judgment and risk to patient in study design.

PMID- 18633060
TI  - Continuous interscalene block for open shoulder surgery.

PMID- 18633061
TI  - A near total spinal anesthetic following a test dose prior to an epidural blood
      patch.

PMID- 18633062
TI  - Ilioinguinal/iliohypogastric blocks: where is the anesthetic injected?

PMID- 18633063
TI  - Anomalous brachial plexus anatomy in the supraclavicular region detected by
      ultrasound.

PMID- 18633064
TI  - Gabapentin for the treatment of glossodynia due to an unusual cause.

PMID- 18633065
TI  - Valsalva's maneuver to assist delivery of a neurocysticercosis cyst from the
      fourth ventricle.

PMID- 18633066
TI  - Health is a human right, right?

PMID- 18633067
TI  - Thro' many dangers, toils, and snares, we have already come.

PMID- 18633068
TI  - Public health education and the world.

PMID- 18633069
TI  - Written informed consent and HIV testing rates: the San Francisco experience.

PMID- 18633070
TI  - New York City's diabetes reporting system helps patients and physicians.

PMID- 18633071
TI  - The case for postdeployment mental health screening was not made.

PMID- 18633072
TI  - Building and sustaining a multiuniversity and multicampus program or school of
      public health.
AB  - Drawing from New Jersey's successful efforts and from other less successful
      efforts, we offer lessons learned for those who will consider a multiuniversity
      and multi-campus program or school of public health. These lessons include
      building a faculty collaboration, senior administrative support, and external
      constituencies and developing a set of documents that institutionalize processes,
      logistics, and other operations. In our experience, building and sustaining
      faculty support is the greatest challenge, followed by protecting existing
      resources and securing additional resources when administrators in the host
      universities change.

PMID- 18633073
TI  - The first mental hospital in China.

PMID- 18633074
TI  - Milton I. Roemer advocate of social medicine, international health, and national
      health insurance.

PMID- 18633075
TI  - Using seminar blogs to enhance student participation and learning in public
      health school classes.
AB  - OBJECTIVES: We evaluated whether "seminar blogs" enhanced learning in a large
      graduate-level introductory public health school class. METHODS: Sixty students
      were divided into 6 online blog groups. Students posted their assignments (case
      analyses, news commentaries), prompting comments from other students. Anonymous
      poll surveys of students were conducted at midpoint and at the end of the course.
      RESULTS: Sixty percent reported that blog participation enriched their learning
      quite a bit, 34% a small amount, and 6% not at all; 54% said that the blogs
      provided opportunities to learn from classmates. When comparing writing on the
      blog to speaking in class, 60% found it easier, 30% about the same, and 10%
      harder. About 65% said that skills attained by participating in blogs were useful
      for current or future work. Major criticisms involved time issues. CONCLUSIONS:
      Small seminar blogs offer opportunities for increased student participation,
      interaction, and learning. To be most effective and appealing, assignments for
      postings need to allow sufficient time for commentary. This educational
      technology has potential to expand the classroom experience and is worthy of
      further development and testing.

PMID- 18633076
TI  - On inspiration and leadership: a conversation with Barbara Sabol, MA, RN, and
      Henrie M. Treadwell, PhD. Interview by Kathleen M. Nelson.
AB  - This article began with Barbara Sabol and Henrie Treadwell's conversations about
      public health leadership and their assertion that today's leaders must take
      bolder steps to ensure health care for the underserved. They discuss a number of
      characteristics that they consider essential if leaders are to reach beyond the
      status quo and create change in their hospitals, health systems, and communities.

PMID- 18633077
TI  - Assessing the legal and ethical preparedness of master of public health
      graduates.
AB  - OBJECTIVES: We explored the relationship between the preparedness of master of
      public health (MPH) graduates in public health law and ethics and their
      completion of courses in these areas. METHODS: We reviewed accredited public
      health schools and programs to assess the supply of required and elective courses
      in law and ethics. In addition, we conducted an Internet-based scenario survey of
      MPH graduates. Survey results were analyzed, and relationships between scenario
      responses and completion of law and ethics courses were assessed. RESULTS: Of the
      93 programs and schools reviewed, 14% required a course in ethics and 16%
      required a course in law. The majority (range = 55%-76%) of the survey
      respondents indicated being "prepared" or "very prepared" for each of the 9
      public health scenarios. There were no significant relationships between scenario
      responses and completion of an ethics course. Responses to 2 scenarios (one
      involving food code violations and one involving a prison population) were
      significantly related to participants' completion of a course in law.
      CONCLUSIONS: Few public health schools and programs require graduate courses in
      ethics and law. Most MPH graduates report being prepared to address public health
      challenges. Additional research is necessary to improve techniques for measuring
      preparedness.

PMID- 18633078
TI  - Waking a sleeping giant: the tobacco industry's response to the polonium-210
      issue.
AB  - The major tobacco manufacturers discovered that polonium was part of tobacco and
      tobacco smoke more than 40 years ago and attempted, but failed, to remove this
      radioactive substance from their products. Internal tobacco industry documents
      reveal that the companies suppressed publication of their own internal research
      to avoid heightening the public's awareness of radioactivity in cigarettes.
      Tobacco companies continue to minimize their knowledge about polonium-210 in
      cigarettes in smoking and health litigation. Cigarette packs should carry a
      radiation-exposure warning label.

PMID- 18633079
TI  - Project Cerberus: tobacco industry strategy to create an alternative to the
      Framework Convention on Tobacco Control.
AB  - Between 1999 and 2001, British American Tobacco, Philip Morris, and Japan Tobacco
      International executed Project Cerberus to develop a global voluntary regulatory
      regime as an alternative to the Framework Convention on Tobacco Control (FCTC).
      They aimed to develop a global voluntary regulatory code to be overseen by an
      independent audit body and to focus attention on youth smoking prevention. The
      International Tobacco Products Marketing Standards announced in September 2001,
      however, did not have the independent audit body. Although the companies did not
      stop the FCTC, they continue to promote the International Tobacco Products
      Marketing Standards youth smoking prevention as an alternative to the FCTC.
      Public health civil society groups should help policymakers and governments
      understand the importance of not working with the tobacco industry.

PMID- 18633080
TI  - Milestones in the process of cessation among novice adolescent smokers.
AB  - OBJECTIVES: We sought to document the sequence and timing of milestones in the
      process of smoking cessation by prospectively studied cessation milestones among
      novice adolescent smokers. METHODS: Participants, aged 12 to 13 years in 1999 (n
      = 1293), completed self-report questionnaires every 3 months during the school
      year over 5 years. We ascertained time after first puff to attain 5 cessation
      milestones among 319 participants who initiated cigarette smoking during follow
      up. RESULTS: The cumulative probability of first reports of a serious desire to
      quit and perceived permanent cessation was 25% at 1.5 months (95% confidence
      interval [CI] = 1.5, 2.5) after the first puff. The first serious quit attempt
      occurred at 2.5 months (95% CI = 2.5, 5.4), lack of confidence about quitting
      followed at 18.4 months (95% CI = 18.4, 26.8), and awareness of the difficulty of
      quitting occurred at 32.2 months (95% CI = 19.2, 38.4). CONCLUSIONS: Desire and
      attempts to quit began soon after smoking onset. Novice smokers progressed
      through several stages in their perception of the difficulty of quitting.
      Increased understanding of the cessation process may help in developing effective
      tobacco control interventions for novice smokers.

PMID- 18633081
TI  - Legal and public health considerations affecting the success, reach, and impact
      of menu-labeling laws.
AB  - Because the rate of consumption of away-from-home meals has increased
      dramatically, the distinction between requiring nutrition information for
      packaged but not restaurant products is no longer reasonable. Public health
      necessitates that nutrition labels must be included with restaurant menus as a
      strategy to educate consumers and address the escalation of obesity. Menu
      labeling laws are being considered at the local, state, and federal levels, but
      the restaurant industry opposes such action. We discuss the public health
      rationale and set forth the government's legal authority for the enactment of
      menu-labeling laws. We further aim to educate the public health community of the
      potential legal challenges to such laws, and we set forth methods for governments
      to survive these challenges by drafting laws according to current legal
      standards.

PMID- 18633082
TI  - Poverty in America: how public health practice can make a difference.
AB  - Health inequities linked to poverty remain entrenched in certain subgroups in the
      United States, despite public health efforts to the contrary. My experiences in
      working with the poor in Nepal and Pakistan informed my later approach to
      addressing health and poverty in the Appalachians of eastern Tennessee. Three
      aspects of this approach include enhancing community power through participation
      in local decisionmaking about health, educating students within the actual
      context of poverty, and increasing local opportunity by employing people from the
      communities of concern to serve as a means to reach those communities.
      Empowerment, education, and opportunity can serve as ways to ameliorate poverty
      and may serve to modulate the persistent underlying conditions that create and
      sustain poverty.

PMID- 18633083
TI  - Psychosocial antecedents and adverse health consequences related to substance
      use.
AB  - OBJECTIVES: We examined the relationship between psychosocial antecedents in
      earlier adolescence and problems related to substance use and related adverse
      health consequence (e.g., respiratory diseases, neurocognitive symptoms, and
      general malaise) in adulthood. We specifically focused on parent-child bonding in
      earlier adolescence and internalizing behaviors in later adolescence and their
      effects on problems related to substance use in the mid-20s and health problems
      in the mid-30s. METHODS: Our team interviewed a community-based sample of 502
      participants over a 30-year period (1975, 1983, 1985-1986, 1997, 2002, and 2005).
      RESULTS: We found a strong relationship between internalizing behaviors in later
      adolescence and adverse health consequences in the mid-30s. Internalizing
      behaviors in later adolescence served as a mediator between low parent-child
      bonding in earlier adolescence and later adverse health consequences. Problems
      related to substance use in the late 20s and early 30s were related directly to
      later adverse health consequences and indirectly as mediators between earlier
      psychosocial difficulties (i.e., internalizing behaviors, externalizing
      behaviors, poor ego integration, and maladaptive coping) and later adverse health
      consequences. CONCLUSIONS: Policies and programs that address parent-child
      bonding and internalizing behaviors should be created to reduce problems related
      to substance use and, ultimately, later health problems.

PMID- 18633084
TI  - Tobacco industry control of menthol in cigarettes and targeting of adolescents
      and young adults.
AB  - OBJECTIVES: We examined whether tobacco manufacturers manipulate the menthol
      content of cigarettes in an effort to target adolescents and young adults.
      METHODS: We analyzed data from tobacco industry documents describing menthol
      product development, results of laboratory testing of US menthol brands, market
      research reports, and the 2006 National Survey on Drug Use and Health. RESULTS:
      The tobacco industry attracted new smokers by promoting cigarettes with lower
      menthol content, which were popular with adolescents and young adults, and
      provided cigarettes with higher menthol content to long-term smokers. Menthol
      cigarette sales remained stable from 2000 to 2005 in the United States, despite a
      22% decline in overall packs sold. CONCLUSIONS: Tobacco companies manipulate the
      sensory characteristics of cigarettes, including menthol content, thereby
      facilitating smoking initiation and nicotine dependence. Menthol brands that have
      used this strategy have been the most successful in attracting youth and young
      adult smokers and have grown in popularity.

PMID- 18633085
TI  - Competencies: from deconstruction to reconstruction and back again, lessons
      learned.
AB  - I address the potential impact of the Association of Schools of Public Health's
      development of a competency model for the graduate Master of Public Health. I
      reflect on the model in relation to the Accreditation Council for Graduate
      Medical Education's adoption of a competency-based model for medical education.
      Six lessons learned by the Accreditation Council for Graduate Medical Education
      that the Association of Schools of Public Health might consider in moving forward
      are how learning outcomes can be enhanced by using competency models, the effect
      of competency development processes in "creating a common language" among
      educators, the benefits and challenges of numerous competencies within a model,
      the usefulness of the Dreyfus model for progressive competency development, the
      need for multiple assessment tools used over time, and the value of learning
      portfolios.

PMID- 18633086
TI  - Neighborhood psychosocial hazards and cardiovascular disease: the Baltimore
      Memory Study.
AB  - OBJECTIVES: We examined associations between cardiovascular disease and
      neighborhood psychosocial hazards, such as violent crime, abandoned buildings,
      and signs of incivility, to evaluate whether features of place are associated
      with older adult health. METHODS: We analyzed first-visit data from the Baltimore
      Memory Study of randomly selected residents aged 50 to 70 years (n=1140) of 65
      contiguous neighborhoods in Baltimore, Maryland. We looked for associations
      between self-reports of history of selected cardiovascular diseases and scores on
      the 12-item neighborhood psychosocial hazards scale. RESULTS: After adjustment
      for established individual risk factors for cardiovascular disease, residents in
      neighborhoods with scores in the highest quartile of the psychosocial hazards
      scale had more than 4 times higher odds of a history of myocardial infarction and
      more than 3 times higher odds of myocardial infarction, stroke, transient
      ischemic attack, or intermittent claudication compared with residents living in
      neighborhoods scoring in the lowest quartile. CONCLUSIONS: Neighborhood
      psychosocial hazards were significantly associated with self-reported
      cardiovascular disease after adjustment for individual-level risk factors. This
      is consistent with the hypothesis that environmental stress plays a role in the
      etiology of cardiovascular disease.

PMID- 18633087
TI  - Improving health behaviors in an African American community: the Charlotte Racial
      and Ethnic Approaches to Community Health project.
AB  - OBJECTIVES: We examined the effect on 3 behavioral risk factors for heart disease
      and diabetes (low fruit and vegetable consumption, low physical activity, and
      cigarette smoking) of an intervention in an African American community in North
      Carolina. METHODS: A community coalition, a lay health advisor program, and
      policy and community environment change strategies were implemented in a
      community of 20,000 African Americans in 2001 to 2005. Health behavior questions
      from the Behavioral Risk Factor Surveillance System survey were administered to a
      cross-section of the community annually. The results were compared with African
      Americans' responses from a statewide survey. RESULTS: All 3 health behaviors
      improved in the study population. Improvements were statistically significant for
      physical activity (P=.02) and smoking (P=.03) among women and for physical
      activity among middle-aged adults (P=.01). Lower baseline physical activity rates
      improved to levels comparable to those of African Americans statewide (2001,
      P<.001; 2005, P=.38), and comparable fruit and vegetable consumption rates became
      significantly higher (2001, P=.68; 2005, P<.001). CONCLUSIONS: Our findings
      support the emerging role of policy and community environment change strategies
      and community participation as promising practices to improve health behaviors in
      African American communities and to reduce health disparities.

PMID- 18633088
TI  - Process is the point: justice and human rights: priority setting and fair
      deliberative process.
AB  - Most people responsible for setting priorities in health have considerable
      expertise relevant to deciding how to use resources effectively and the kinds of
      improvements that should be emphasized. Most are also concerned with distributing
      improvements equitably. Accordingly, they often invoke human rights or principles
      of distributive justice to legitimize choices that create winners and losers. We
      propose an approach that draws on the strengths of both perspectives as a way to
      add legitimacy to efforts to set priorities in health. Our proposal provides a
      process for setting priorities but is not a formula or an algorithm for
      generating particular priorities. We propose an approach that would do away with
      the process through which priorities are set and decisions made, and suggest the
      value of a focus on the process of legitimizing these decisions.

PMID- 18633089
TI  - US child labor violations in the retail and service industries: findings from a
      national survey of working adolescents.
AB  - OBJECTIVES: We investigated child labor violations among US adolescents working
      in the retail and service industries. METHODS: We used interview data from a
      nationally representative sample of working adolescents, and investigated reports
      of select child labor violations (e.g., hours, equipment, and work permits). We
      computed weighted percentages of respondents reporting each type of discrete (and
      aggregated) violation. RESULTS: Nearly 37% of respondents reported a violation of
      the hazardous occupations orders (i.e., prohibited jobs or use of equipment), and
      40% reported a work permit violation. Fewer than 2% reported working more than
      the maximum weekly hours allowed during the school year, but 11% reported working
      past the latest hour allowed on a school night, and 15% reported working off the
      clock. CONCLUSIONS: Significant numbers of US adolescents are employed in
      violation of the child labor laws and as a result are exposed to safety risks.
      Although our data did not allow for an analysis of enforcement, our findings
      demonstrate gaps in employer compliance with the law. We suggest that closer
      attention to enforcement policy and practice is needed.

PMID- 18633090
TI  - US health educators' likelihood of adopting genomic competencies into health
      promotion.
AB  - OBJECTIVES: We examined US health educators' likelihood of adopting genomic
      competencies--specific skills and knowledge in public health genomics--into
      health promotion and the factors influencing such likelihood. METHODS: We
      developed and tested a model to assess likelihood to adopt genomic competencies.
      Data from 1607 health educators nationwide were collected through a Web-based
      survey. The model was tested through structural equation modeling. RESULTS:
      Although participants in our study were not very likely to adopt genomic
      competencies into their practice, the data supported the proposed model.
      Awareness, attitudes, and self-efficacy significantly affected health educators'
      likelihood to incorporate genomic competencies. The model explained 60.3% of the
      variance in likelihood to incorporate genomic competencies. Participants'
      perceived compatibility between public health genomics and their professional and
      personal roles, their perceptions of genomics as complex, and the communication
      channels used to learn about public health genomics significantly related to
      genomic knowledge and attitudes. CONCLUSIONS: Because US health educators in our
      sample do not appear ready for their professional role in genomics, future
      research and public health work-force training are needed.

PMID- 18633091
TI  - Mental health in Sumatra after the tsunami.
AB  - OBJECTIVES: We assessed the levels and correlates of posttraumatic stress
      reactivity (PTSR) of more than 20,000 adult tsunami survivors by analyzing survey
      data from coastal Aceh and North Sumatra, Indonesia. METHODS: A population
      representative sample of individuals interviewed before the tsunami was traced in
      2005 to 2006. We constructed 2 scales measuring PTSR by using 7 symptom items
      from the Post Traumatic Stress Disorder (PTSD) Checklist-Civilian Version. One
      scale measured PTSR at the time of interview, and the other measured PTSR at the
      point of maximum intensity since the disaster. RESULTS: PTSR scores were highest
      for respondents from heavily damaged areas. In all areas, scores declined over
      time. Gender and age were significant predictors of PTSR; markers of
      socioeconomic status before the tsunami were not. Exposure to traumatic events,
      loss of kin, and property damage were significantly associated with higher PTSR
      scores. CONCLUSIONS: The tsunami produced posttraumatic stress reactions across a
      wide region of Aceh and North Sumatra. Public health will be enhanced by the
      provision of counseling services that reach not only people directly affected by
      the tsunami but also those living beyond the area of immediate impact.

PMID- 18633092
TI  - Untapped resources: exploring the need to invest in doctor of public health
      degree training and leadership development.

PMID- 18633093
TI  - Development of a core competency model for the master of public health degree.
AB  - Core competencies have been used to redefine curricula across the major health
      professions in recent decades. In 2006, the Association of Schools of Public
      Health identified core competencies for the master of public health degree in
      graduate schools and programs of public health. We provide an overview of the
      model development process and a listing of 12 core domains and 119 competencies
      that can serve as a resource for faculty and students for enhancing the quality
      and accountability of graduate public health education and training. The primary
      vision for the initiative is the graduation of professionals who are more fully
      prepared for the many challenges and opportunities in public health in the
      forthcoming decade.

PMID- 18633095
TI  - From mosques to classrooms: mobilizing the community to enhance case detection of
      tuberculosis.
AB  - In response to the global challenge of inadequate case detection of tuberculosis
      (TB), the Fund for Innovative DOTS Expansion through Local Initiatives to Stop
      Tuberculosis (FIDELIS) was developed in 2003 to rapidly assess and implement
      innovative approaches to increase the detection of new smear-positive TB cases.
      As previously reported, a wide range of target populations and interventions has
      been incorporated into successful FIDELIS projects.

PMID- 18633094
TI  - The changing pattern of doctoral education in public health from 1985 to 2006 and
      the challenge of doctoral training for practice and leadership.
AB  - We examined trends in doctoral education in public health and the challenges
      facing practice-oriented doctor of public health (DrPH) programs. We found a
      rapid rise in the numbers of doctoral programs and students. Most of the increase
      was in PhD students who in 2006 composed 73% of the total 5247 current public
      health doctoral students, compared with 53% in 1985. There has also been a
      substantial increase (40%) in students in DrPH programs since 2002. Challenges
      raised by the increased demand for DrPH practice-oriented education relate to
      admissions, curriculum, assessment processes, and faculty hiring and promotion.
      We describe approaches to practice-based doctoral education taken by three
      schools of public health.

PMID- 18633096
TI  - Core academic competencies for master of public health students: one health
      department practitioner's perspective.
AB  - The Association of Schools of Public Health (ASPH) has developed a comprehensive
      set of core academic competencies for master of public health (MPH) graduates.
      The ASPH core MPH competencies delineate fundamental knowledge, attitudes, and
      skills that every MPH student, regardless of their major field, should possess
      upon graduation. From a public health agency perspective, this is a promising
      development. The ASPH MPH core competencies are complementary to the Core
      Competencies for Public Health Practice developed by the Council on Linkages
      Between Academia and Public Health Practice. Although a useful development, the
      academic MPH core competencies should not be confused with a conclusive
      definition of what constitutes a public health professional.

PMID- 18633097
TI  - The context for choice: health implications of targeted food and beverage
      marketing to African Americans.
AB  - Targeted marketing of high-calorie foods and beverages to ethnic minority
      populations, relative to more healthful foods, may contribute to ethnic
      disparities in obesity and other diet-related chronic conditions. We conducted a
      systematic review of studies published in June 1992 through 2006 (n = 20) that
      permitted comparison of food and beverage marketing to African Americans versus
      Whites and others. Eight studies reported on product promotions, 11 on retail
      food outlet locations, and 3 on food prices. Although the evidence base has
      limitations, studies indicated that African Americans are consistently exposed to
      food promotion and distribution patterns with relatively greater potential
      adverse health effects than are Whites. The limited evidence on price disparities
      was inconclusive.

PMID- 18633098
TI  - The lead industry and lead water pipes "A Modest Campaign".
AB  - Lead pipes for carrying drinking water were well recognized as a cause of lead
      poisoning by the late 1800s in the United States. By the 1920s, many cities and
      towns were prohibiting or restricting their use. To combat this trend, the lead
      industry carried out a prolonged and effective campaign to promote the use of
      lead pipes. Led by the Lead Industries Association (LIA), representatives were
      sent to speak with plumbers' organizations, local water authorities, architects,
      and federal officials. The LIA also published numerous articles and books that
      extolled the advantages of lead over other materials and gave practical advice on
      the installation and repair of lead pipes. The LIA's activities over several
      decades therefore contributed to the present-day public health and economic cost
      of lead water pipes.

PMID- 18633099
TI  - Approaching health disparities from a population perspective: the National
      Institutes of Health Centers for Population Health and Health Disparities.
AB  - Addressing health disparities has been a national challenge for decades. The
      National Institutes of Health-sponsored Centers for Population Health and Health
      Disparities are the first federal initiative to support transdisciplinary
      multilevel research on the determinants of health disparities. Their novel
      research approach combines population, clinical, and basic science to elucidate
      the complex determinants of health disparities. The centers are partnering with
      community-based, public, and quasi-public organizations to disseminate scientific
      findings and guide clinical practice in communities. In turn, communities and
      public health agents are shaping the research. The relationships forged through
      these complex collaborations increase the likelihood that the centers' scientific
      findings will be relevant to communities and contribute to reductions in health
      disparities.

PMID- 18633100
TI  - Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and
      insulin sensitivity.
AB  - OBJECTIVE: To ascertain the importance and mechanisms underlying the role of
      brain glucagon-like peptide (GLP)-1 in the control of metabolic and
      cardiovascular function. GLP-1 is a gut hormone secreted in response to oral
      glucose absorption that regulates glucose metabolism and cardiovascular function.
      GLP-1 is also produced in the brain, where its contribution to central regulation
      of metabolic and cardiovascular homeostasis remains incompletely understood.
      RESEARCH DESIGN AND METHODS: Awake free-moving mice were infused with the GLP-1
      receptor agonist exendin-4 (Ex4) into the lateral ventricle of the brain in the
      basal state or during hyperinsulinemic eu-/hyperglycemic clamps. Arterial femoral
      blood flow, whole-body insulin-stimulated glucose utilization, and heart rates
      were continuously recorded. RESULTS: A continuous 3-h brain infusion of Ex4
      decreased femoral arterial blood flow and whole-body glucose utilization in the
      awake free-moving mouse clamped in a hyperinsulinemic-hyperglycemic condition,
      only demonstrating that this effect was strictly glucose dependent. However, the
      heart rate remained unchanged. The metabolic and vascular effects of Ex4 were
      markedly attenuated by central infusion of the GLP-1 receptor (GLP-1R) antagonist
      exendin-9 (Ex9) and totally abolished in GLP-1 receptor knockout mice. A
      correlation was observed between the metabolic rate and the vascular flow in
      control and Ex4-infused mice, which disappeared in Ex9 and GLP-1R knockout mice.
      Moreover, hypothalamic nitric oxide synthase activity and the concentration of
      reactive oxygen species (ROS) were also reduced in a GLP-1R-dependent manner,
      whereas the glutathione antioxidant capacity was increased. Central GLP-1
      activated vagus nerve activity, and complementation with ROS donor dose
      dependently reversed the effect of brain GLP-1 signaling on peripheral blood
      flow. CONCLUSIONS: Our data demonstrate that central GLP-1 signaling is an
      essential component of circuits integrating cardiovascular and metabolic
      responses to hyperglycemia.

PMID- 18633101
TI  - Elevated toll-like receptor 4 expression and signaling in muscle from insulin
      resistant subjects.
AB  - OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of
      free fatty acid (FFA)-induced insulin resistance by activating inflammatory
      pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB
      (NFkappaB). However, it is not known whether insulin-resistant subjects have
      abnormal TLR4 signaling. We examined whether insulin-resistant subjects have
      abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal
      muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content
      were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic
      subjects. A primary human myotube culture system was used to examine whether FFAs
      stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4
      expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had
      significantly elevated TLR4 gene expression and protein content in muscle. TLR4
      muscle protein content correlated with the severity of insulin resistance. Obese
      and type 2 diabetic subjects also had lower IkappaBalpha content, an indication
      of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB
      signaling was accompanied by elevated expression of the NFkappaB-regulated genes
      interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes,
      acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4
      prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway.
      Increased TLR4 content and gene expression observed in muscle from insulin
      resistant subjects were reproduced by treating myotubes from lean, normal-glucose
      tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene
      expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS-
      Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA
      levels, may contribute to the pathogenesis of insulin resistance in humans.

PMID- 18633103
TI  - Increased expression of CCL2 in insulin-producing cells of transgenic mice
      promotes mobilization of myeloid cells from the bone marrow, marked insulitis,
      and diabetes.
AB  - OBJECTIVE: To define the mechanisms underlying the accumulation of
      monocytes/macrophages in the islets of Langerhans. RESEARCH DESIGN AND METHODS:
      We tested the hypothesis that macrophage accumulation into the islets is caused
      by overexpression of the chemokine CCL2. To test this hypothesis, we generated
      transgenic mice and evaluated the cellular composition of the islets by
      immunohistochemistry and flow cytometry. We determined serum levels of CCL2 by
      enzyme-linked immunosorbent assay, determined numbers of circulating monocytes,
      and tested whether CCL2 could mobilize monocytes from the bone marrow directly.
      We examined development of diabetes over time and tested whether CCL2 effects
      could be eliminated by deletion of its receptor, CCR2. RESULTS: Expression of
      CCL2 by beta-cells was associated with increased numbers of monocytes in
      circulation and accumulation of macrophages in the islets of transgenic mice.
      These changes were promoted by combined actions of CCL2 at the level of the bone
      marrow and the islets and were not seen in animals in which the CCL2 receptor
      (CCR2) was inactivated. Mice expressing higher levels of CCL2 in the islets
      developed diabetes spontaneously. The development of diabetes was correlated with
      the accumulation of large numbers of monocytes in the islets and did not depend
      on T- and B-cells. Diabetes could also be induced in normoglycemic mice
      expressing low levels of CCL2 by increasing the number of circulating myeloid
      cells. CONCLUSIONS: These results indicate that CCL2 promotes monocyte
      recruitment by acting both locally and remotely and that expression of CCL2 by
      insulin-producing cells can lead to insulitis and islet destruction.

PMID- 18633104
TI  - Impaired glucose tolerance and insulin resistance are associated with increased
      adipose 11beta-hydroxysteroid dehydrogenase type 1 expression and elevated
      hepatic 5alpha-reductase activity.
AB  - OBJECTIVE: The precise molecular mechanisms contributing to the development of
      insulin resistance, impaired glucose tolerance (IGT), and type 2 diabetes are
      largely unknown. Altered endogenous glucocorticoid metabolism, including 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which generates active
      cortisol from cortisone, and 5alpha-reductase (5alphaR), which inactivates
      cortisol, has been implicated. RESEARCH DESIGN AND METHODS: A total of 101 obese
      patients (mean age 48 +/- 7 years, BMI 34.4 +/- 4.3 kg/m(2), 66 women, 35 men)
      underwent 75-g oral glucose tolerance testing (OGTT), body composition analysis
      (dual-energy X-ray absorptiometry), assessment of glucocorticoid metabolism (24-h
      urine steroid metabolite analysis by gas chromatography/mass spectrometry), and
      subcutaneous abdominal adipose tissue biopsies. RESULTS: A total of 22.7% of
      women had IGT compared with 34.2% of men. Two women and five men were diagnosed
      with type 2 diabetes. In women, adipose 11beta-HSD1 expression was increased in
      patients with IGT and correlated with glucose levels across the OGTT (R = 0.44, P
      < 0.001) but was independent of fat mass. Total glucocorticoid secretion was
      higher in men with and without IGT (normal 13,743 +/- 863 vs. 7,453 +/- 469
      microg/24 h, P < 0.001; IGT 16,871 +/- 2,113 vs. 10,133 +/- 1,488 microg/24 h, P
      < 0.05), and in women, it was higher in those with IGT (7,453 +/- 469 vs. 10,133
      +/- 1,488 microg/24 h, P < 0.001). In both sexes, 5alphaR activity correlated
      with fasting insulin (men R = 0.53, P = 0.003; women R = 0.33, P = 0.02), insulin
      secretion across an OGTT (men R = 0.46, P = 0.01; women R = 0.40, P = 0.004), and
      homeostasis model assessment of insulin resistance (men R = 0.52, P = 0.004;
      women R = 0.33, P = 0.02). CONCLUSIONS: Increased adipose 11beta-HSD1 expression
      in women may contribute to glucose intolerance. Enhanced 5alphaR activity in both
      sexes is associated with insulin resistance but not body composition. Augmented
      glucocorticoid inactivation may serve as a compensatory, protective mechanism to
      preserve insulin sensitivity.

PMID- 18633105
TI  - Simultaneous islet and kidney transplantation in seven patients with type 1
      diabetes and end-stage renal disease using a glucocorticoid-free
      immunosuppressive regimen with alemtuzumab induction.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficiency and safety of
      simultaneous islet and kidney transplantation in patients with type 1 diabetes
      and end-stage renal disease using a glucocorticoid-free immunosuppressive regimen
      with alemtuzumab induction. RESEARCH DESIGN AND METHODS: Seven patients with type
      1 diabetes and end-stage renal failure were transplanted with allogenic islets
      and kidneys procured from brain-dead donors. To prevent organ rejection, patients
      received alemtuzumab for induction immunosuppression, followed by sirolimus and
      tacrolimus. No glucocorticoids were given at any time. RESULTS: The median
      duration of follow-up was 18.3 months (range 13-31). Kidney survival was 100%.
      Four patients became insulin independent at 1 year. The other three reduced
      insulin use to less than 25% of the amount required before transplantation. Serum
      C-peptide levels were significantly greater posttransplant in all patients,
      indicating continued islet function. No major procedure-related complications
      were observed. CONCLUSIONS: Our results demonstrate that a steroid-free
      immunosuppressive regimen consisting of alemtuzumab, sirolimus, and tacrolimus is
      feasible for simultaneous islet and kidney transplantation. The question of
      whether this induction regimen is superior to more standard induction deserves
      large studies.

PMID- 18633106
TI  - Integrin-associated protein association with SRC homology 2 domain containing
      tyrosine phosphatase substrate 1 regulates igf-I signaling in vivo.
AB  - OBJECTIVE: Smooth muscle cell (SMC) maintained in medium containing normal levels
      of glucose do not proliferate in response to IGF-I, whereas cells maintained in
      medium containing 25 mmol/l glucose can respond. The aim of this study was to
      determine whether signaling events that have been shown to be required for
      stimulation of SMC growth were regulated by glucose concentrations in vivo.
      RESEARCH DESIGN AND METHODS: We compared IGF-I-stimulated signaling events and
      growth in the aortic smooth muscle cells from normal and hyperglycemic mice.
      RESULTS: We determined that, in mice, hyperglycemia was associated with an
      increase in formation of the integrin-associated protein (IAP)/Src homology 2
      domaine containing tyrosine phosphatase substrate 1 (SHPS-1) complex. There was a
      corresponding increase in Shc recruitment to SHPS-1 and Shc phosphorylation in
      response to IGF-I. There was also an increase in mitogen-activated protein kinase
      activation and SMC proliferation. The increase in IAP association with SHPS-1 in
      hyperglycemia appeared to be due to the protection of IAP from cleavage that
      occurred during exposure to normal glucose. In addition, we demonstrated that the
      protease responsible for IAP cleavage was matrix metalloprotease-2. An anti-IAP
      antibody that disrupted the IAP-SHPS-1 association resulted in complete
      inhibition of IGF-I-stimulated proliferation. CONCLUSIONS: Taken together, our
      results support a model in which hyperglycemia is associated with a reduction in
      IAP cleavage, thus allowing the formation of the IAP-SHPS-1 signaling complex
      that is required for IGF-I-stimulated proliferation of SMC.

PMID- 18633107
TI  - G/T substitution in intron 1 of the UNC13B gene is associated with increased risk
      of nephropathy in patients with type 1 diabetes.
AB  - OBJECTIVE: Genetic and environmental factors modulate the susceptibility to
      diabetic nephropathy, as initiating and/or progression factors. The objective of
      the European Rational Approach for the Genetics of Diabetic Complications
      (EURAGEDIC) study is to identify nephropathy susceptibility genes. We report
      molecular genetic studies for 127 candidate genes for nephropathy. RESEARCH
      DESIGN AND METHODS: Polymorphisms were identified through sequencing of promoter,
      exon, and flanking intron gene regions and a database search. A total of 344
      nonredundant SNPs and nonsynonymous variants were tested for association with
      diabetic nephropathy (persistent albuminuria >/=300 mg/24 h) in a large type 1
      diabetes case/control (1,176/1,323) study from three European populations.
      RESULTS: Only one SNP, rs2281999, located in the UNC13B gene, was significantly
      associated with nephropathy after correction for multiple testing. Analyses of 21
      additional markers fully characterizing the haplotypic variability of the UNC13B
      gene showed consistent association of SNP rs13293564 (G/T) located in intron 1 of
      the gene with nephropathy in the three populations. The odds ratio (OR) for
      nephropathy associated with the TT genotype was 1.68 (95% CI 1.29-2.19) (P = 1.0
      x 10(-4)). This association was replicated in an independent population of 412
      case subjects and 614 control subjects (combined OR of 1.63 [95% CI 1.30-2.05], P
      = 2.3 x 10(-5)). CONCLUSIONS: We identified a polymorphism in the UNC13B gene
      associated with nephropathy. UNC13B mediates apopotosis in glomerular cells in
      the presence of hyperglycemia, an event occurring early in the development of
      nephropathy. We propose that this polymorphism could be a marker for the
      initiation of nephropathy. However, further studies are needed to clarify the
      role of UNC13B in nephropathy.

PMID- 18633108
TI  - Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are
      associated with type 2 diabetes and impaired fasting glucose in a Chinese Han
      population.
AB  - OBJECTIVE: Genome-wide association studies have identified common variants in
      CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that
      significantly increase the risk of type 2 diabetes. We aimed to replicate these
      observations in a population-based cohort of Chinese Hans and examine the
      associations of these variants with type 2 diabetes and diabetes-related
      phenotypes. RESEARCH DESIGN AND METHODS: We genotyped 17 single nucleotide
      polymorhisms (SNPs) in 3,210 unrelated Chinese Hans, including 424 participants
      with type 2 diabetes, 878 with impaired fasting glucose (IFG), and 1,908 with
      normal fasting glucose. RESULTS: We confirmed the associations between type 2
      diabetes and variants near CDKAL1 (odds ratio 1.49 [95% CI 1.27-1.75]; P = 8.91 x
      10(-7)) and CDKN2A/B (1.31 [1.12-1.54]; P = 1.0 x 10(-3)). We observed
      significant association of SNPs in IGF2BP2 (1.17 [1.03-1.32]; P = 0.014) and
      SLC30A8 (1.12 [1.01-1.25]; P = 0.033) with combined IFG/type 2 diabetes. The SNPs
      in CDKAL1, IGF2BP2, and SLC30A8 were also associated with impaired beta-cell
      function estimated by homeostasis model assessment of beta-cell function. When
      combined, each additional risk allele from CDKAL1-rs9465871, CDKN2A/B-rs10811661,
      IGF2BP2-rs4402960, and SLC30A8-rs13266634 increased the risk for type 2 diabetes
      by 1.24-fold (P = 2.85 x 10(-7)) or for combined IFG/type 2 diabetes by 1.21-fold
      (P = 6.31 x 10(-11)). None of the SNPs in EXT2 or LOC387761 exhibited significant
      association with type 2 diabetes or IFG. Significant association was observed
      between the HHEX/IDE SNPs and type 2 diabetes in individuals from Shanghai only
      (P < 0.013) but not in those from Beijing (P > 0.33). CONCLUSIONS: Our results
      indicate that in Chinese Hans, common variants in CDKAL1, CDKN2A/B, IGF2BP2, and
      SLC30A8 loci independently or additively contribute to type 2 diabetes risk,
      likely mediated through beta-cell dysfunction.

PMID- 18633109
TI  - Cerebral blood flow and cerebral edema in rats with diabetic ketoacidosis.
AB  - OBJECTIVE: Cerebral edema (CE) is a potentially life-threatening complication of
      diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA
      treatment have been considered responsible, but recent data instead suggest that
      cerebral hypoperfusion may be involved and that activation of cerebral ion
      transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however,
      has not been previously demonstrated. We investigated CBF and edema formation in
      a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K
      Cl cotransport. RESEARCH DESIGN AND METHODS: Juvenile rats with streptozotocin
      induced DKA were treated with intravenous saline and insulin, similar to human
      treatment protocols. CBF was determined by magnetic resonance (MR) perfusion
      weighted imaging before and during treatment, and CE was assessed by determining
      apparent diffusion coefficients (ADCs) using MR diffusion-weighted imaging.
      RESULTS: CBF was significantly reduced in DKA and was responsive to alterations
      in pCO(2). ADC values were reduced, consistent with cell swelling. The reduction
      in ADCs correlated with dehydration, as reflected in blood urea nitrogen
      concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without
      significantly changing CBF, while saline/insulin caused a rapid rise in CBF and a
      gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin showed
      a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF
      than those observed with saline/insulin alone. CONCLUSIONS: These data
      demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before
      treatment and suggest that blocking Na-K-Cl cotransport may reduce cerebral cell
      swelling.

PMID- 18633110
TI  - Alterations in microRNA expression contribute to fatty acid-induced pancreatic
      beta-cell dysfunction.
AB  - OBJECTIVE: Visceral obesity and elevated plasma free fatty acids are predisposing
      factors for type 2 diabetes. Chronic exposure to these lipids is detrimental for
      pancreatic beta-cells, resulting in reduced insulin content, defective insulin
      secretion, and apoptosis. We investigated the involvement in this phenomenon of
      microRNAs (miRNAs), a class of noncoding RNAs regulating gene expression by
      sequence-specific inhibition of mRNA translation. RESEARCH DESIGN AND METHODS: We
      analyzed miRNA expression in insulin-secreting cell lines or pancreatic islets
      exposed to palmitate for 3 days and in islets from diabetic db/db mice. We
      studied the signaling pathways triggering the changes in miRNA expression and
      determined the impact of the miRNAs affected by palmitate on insulin secretion
      and apoptosis. RESULTS: Prolonged exposure of the beta-cell line MIN6B1 and
      pancreatic islets to palmitate causes a time- and dose-dependent increase of
      miR34a and miR146. Elevated levels of these miRNAs are also observed in islets of
      diabetic db/db mice. miR34a rise is linked to activation of p53 and results in
      sensitization to apoptosis and impaired nutrient-induced secretion. The latter
      effect is associated with inhibition of the expression of vesicle-associated
      membrane protein 2, a key player in beta-cell exocytosis. Higher miR146 levels do
      not affect the capacity to release insulin but contribute to increased apoptosis.
      Treatment with oligonucleotides that block miR34a or miR146 activity partially
      protects palmitate-treated cells from apoptosis but is insufficient to restore
      normal secretion. CONCLUSIONS: Our findings suggest that at least part of the
      detrimental effects of palmitate on beta-cells is caused by alterations in the
      level of specific miRNAs.

PMID- 18633111
TI  - Diurnal variation of human sweet taste recognition thresholds is correlated with
      plasma leptin levels.
AB  - OBJECTIVE: It has recently been proposed that the peripheral taste organ is one
      of the targets for leptin. In lean mice, leptin selectively suppresses gustatory
      neural and behavioral responses to sweet compounds without affecting responses to
      other taste stimuli, whereas obese diabetic db/db mice with defects in leptin
      receptor lack this leptin suppression on sweet taste. Here, we further examined
      potential links between leptin and sweet taste in humans. RESEARCH DESIGN AND
      METHODS: A total of 91 nonobese subjects were used to determine recognition
      thresholds using a standard stair-case methodology for various taste stimuli.
      Plasma leptin levels were determined by an enzyme-linked immunosorbent assay at
      several timepoints during the day under normal and restricted-meal conditions.
      RESULTS: The recognition thresholds for sweet compounds exhibited a diurnal
      variation from 0800 to 2200 h that parallels variation for leptin levels, with
      the lowest thresholds in the morning and the highest thresholds at night. This
      diurnal variation is sweet-taste selective-it was not observed in thresholds for
      other taste stimuli (NaCl, citric acid, quinine, and mono-sodium glutamate). The
      diurnal variation for sweet thresholds in the normal feeding condition (three
      meals) was independent of meal timing and thereby blood glucose levels.
      Furthermore, when leptin levels were phase-shifted following imposition of one or
      two meals per day, the diurnal variation of thresholds for sweet taste shifted in
      parallel. CONCLUSIONS: This synchronization of diurnal variation in leptin levels
      and sweet taste recognition thresholds suggests a mechanistic connection between
      these two variables in humans.

PMID- 18633112
TI  - Muscle-specific IRS-1 Ser->Ala transgenic mice are protected from fat-induced
      insulin resistance in skeletal muscle.
AB  - OBJECTIVE: Insulin resistance in skeletal muscle plays a critical role in the
      pathogenesis of type 2 diabetes, yet the cellular mechanisms responsible for
      insulin resistance are poorly understood. In this study, we examine the role of
      serine phosphorylation of insulin receptor substrate (IRS)-1 in mediating fat
      induced insulin resistance in skeletal muscle in vivo. RESEARCH DESIGN AND
      METHODS: To directly assess the role of serine phosphorylation in mediating fat
      induced insulin resistance in skeletal muscle, we generated muscle-specific IRS-1
      Ser(302), Ser(307), and Ser(612) mutated to alanine (Tg IRS-1 Ser-->Ala) and IRS
      1 wild-type (Tg IRS-1 WT) transgenic mice and examined insulin signaling and
      insulin action in skeletal muscle in vivo. RESULTS: Tg IRS-1 Ser-->Ala mice were
      protected from fat-induced insulin resistance, as reflected by lower plasma
      glucose concentrations during a glucose tolerance test and increased insulin
      stimulated muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. In
      contrast, Tg IRS-1 WT mice exhibited no improvement in glucose tolerance after
      high-fat feeding. Furthermore, Tg IRS-1 Ser-->Ala mice displayed a significant
      increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase
      activity and Akt phosphorylation in skeletal muscle in vivo compared with WT
      control littermates. CONCLUSIONS: These data demonstrate that serine
      phosphorylation of IRS-1 plays an important role in mediating fat-induced insulin
      resistance in skeletal muscle in vivo.

PMID- 18633113
TI  - Plasma fetuin-A levels and the risk of type 2 diabetes.
AB  - OBJECTIVE: The liver-secreted protein fetuin-A induces insulin resistance in
      animals, and circulating fetuin-A is elevated in insulin resistance and fatty
      liver in humans. We investigated whether plasma fetuin-A levels predict the
      incidence of type 2 diabetes in a large prospective, population-based study.
      RESEARCH DESIGN AND METHODS: A case-cohort study within the European Prospective
      Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 27,548
      subjects was designed. We randomly selected a subcohort of 2,500 individuals of
      whom 2,164 were diabetes free at baseline and had anamnestic, anthropometrical,
      and metabolic data for analysis. Of the 849 incident diabetic case subjects
      identified in the full cohort during 7 years of follow-up, 703 remained for
      analyses after similar exclusions. RESULTS: Plasma fetuin-A levels were
      positively associated with diabetes risk after adjustment for age (relative risk
      [RR] for extreme quintiles 1.75 [95% CI 1.32-2.31]; RR for 10 mug/ml 1.04 [1.03
      1.06]). The association remained significant after adjustment for sex, BMI, waist
      circumference, and lifestyle risk factors (RR for 10 mug/ml 1.03 [1.01-1.06]).
      Adjustment for glucose, triglycerides, HDL cholesterol, A1C, gamma
      glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment
      for these biomarkers did not appreciably change this result (RR for 10 mug/ml
      full adjusted model 1.05 [1.02-1.07]). Furthermore, fetuin-A was associated with
      increased diabetes risk particularly in individuals with elevated plasma glucose.
      CONCLUSIONS: Our data suggest that fetuin-A is an independent risk factor of type
      2 diabetes.

PMID- 18633114
TI  - Impaired collateral recruitment and outward remodeling in experimental diabetes.
AB  - OBJECTIVE: In this study, the effect of chronic hyperglycemia on acute ligation
      induced collateral vasodilation, on monocyte chemotaxis, and on structural
      outward remodeling of collaterals was investigated. RESEARCH DESIGN AND METHODS:
      Femoral artery ligation was performed 8 weeks after alloxan or saline treatment
      in New Zealand White rabbits. Angiography was performed directly, 1 and 3 weeks
      after ligation. These angiographic recordings were used to quantify number of
      collaterals, lumen, and blood volume index. Reactive hyperemia response was
      tested by intramuscular laser Doppler measurements. Subsequently, blood was
      sampled from the aorta for monocyte chemotaxis. RESULTS: Ligation resulted in
      markedly lower acute collateral vasodilation in diabetic compared with control
      rabbits. Also, hyperemic vasodilatory response to local ischemia was impaired in
      diabetic rabbits. This difference persisted at 1 and 3 weeks after ligation, with
      a lower number of visible collaterals. In addition, the collateral lumen was
      markedly lower in diabetic rabbits after the maturation phase. Likewise, a
      reduced blood volume index in the region of growing collaterals was observed in
      diabetic animals. The monocyte migration toward vascular endothelial growth
      factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic
      rabbits. CONCLUSIONS: This study demonstrates that chronic hyperglycemia
      negatively affects the different phases of arteriogenesis: 1) impaired shear
      induced vasodilatation; 2) impaired outward collateral growth, reflected in the
      number of collaterals and blood volume index; and 3) inhibition of monocyte
      chemotaxis. Impairments were most evident in the acute phase of arteriogenesis.
      Therapies aimed at restoring acute collateral recruitment, such as vasodilators,
      may be of interest to improve collateral function in diabetes.

PMID- 18633115
TI  - Sulfasalazine blocks the development of tactile allodynia in diabetic rats.
AB  - OBJECTIVE: Diabetic neuropathy is manifested either by loss of nociception
      (painless syndrome) or by mechanical hyperalgesia and tactile allodynia (pain in
      response to nonpainful stimuli). While therapies with vasodilators or
      neurotrophins reverse some functional and metabolic abnormalities in diabetic
      nerves, they only partially ameliorate neuropathic pain. The reported link
      between nociception and targets of the anti-inflammatory drug sulfasalazine
      prompted us to investigate its effect on neuropathic pain in diabetes. RESEARCH
      DESIGN AND METHODS: We examined the effects of sulfasalazine, salicylates, and
      the poly(ADP-ribose) polymerase-1 inhibitor PJ34 on altered nociception in
      streptozotocin-induced diabetic rats. We also evaluated the levels of
      sulfasalazine targets in sciatic nerves and dorsal root ganglia (DRG) of treated
      animals. Finally, we analyzed the development of tactile allodynia in diabetic
      mice lacking expression of the sulfasalazine target nuclear factor-kappaB (NF
      kappaB) p50. RESULTS: Sulfasalazine completely blocked the development of tactile
      allodynia in diabetic rats, whereas relatively minor effects were observed with
      other salicylates and PJ34. Along with the behavioral findings, sciatic nerves
      and DRG from sulfasalazine-treated diabetic rats displayed a decrease in NF
      kappaB p50 expression compared with untreated diabetic animals. Importantly, the
      absence of tactile allodynia in diabetic NF-kappaB p50(-/-) mice supported a role
      for NF-kappaB in diabetic neuropathy. Sulfasalazine treatment also increased
      inosine levels in sciatic nerves of diabetic rats. CONCLUSIONS: The complete
      inhibition of tactile allodynia in experimental diabetes by sulfasalazine may
      stem from its ability to regulate both NF-kappaB and inosine. Sulfasalazine might
      be useful in the treatment of nociceptive alterations in diabetic patients.

PMID- 18633116
TI  - Spontaneous diabetes in hemizygous human amylin transgenic mice that developed
      neither islet amyloid nor peripheral insulin resistance.
AB  - OBJECTIVES: We sought to 1) Determine whether soluble-misfolded amylin or
      insoluble-fibrillar amylin may cause or result from diabetes in human amylin
      transgenic mice and 2) determine the role, if any, that insulin resistance might
      play in these processes. RESEARCH DESIGN AND METHODS: We characterized the
      phenotypes of independent transgenic mouse lines that display pancreas-specific
      expression of human amylin or a nonaggregating homolog, [(25,28,29)Pro]human
      amylin, in an FVB/n background. RESULTS: Diabetes occurred in hemizygous human
      amylin transgenic mice from 6 weeks after birth. Glucose tolerance was impaired
      during the mid- and end-diabetic phases, in which progressive beta-cell loss
      paralleled decreasing pancreatic and plasma insulin and amylin. Peripheral
      insulin resistance was absent because glucose uptake rates were equivalent in
      isolated soleus muscles from transgenic and control animals. Even in advanced
      diabetes, islets lacked amyloid deposits. In islets from nontransgenic mice,
      glucagon and somatostatin cells were present mainly at the periphery and insulin
      cells were mainly in the core; in contrast, all three cell types were distributed
      throughout the islet in transgenic animals. [(25,28,29)Pro]human amylin
      transgenic mice developed neither beta-cell degeneration nor glucose intolerance.
      CONCLUSIONS: Overexpression of fibrillogenic human amylin in these human amylin
      transgenic mice caused beta-cell degeneration and diabetes through mechanisms
      independent from both peripheral insulin resistance and islet amyloid. These
      findings are consistent with beta-cell death evoked by misfolded but soluble
      cytotoxic species, such as those formed by human amylin in vitro.

PMID- 18633117
TI  - Activation of NF-E2-related factor-2 reverses biochemical dysfunction of
      endothelial cells induced by hyperglycemia linked to vascular disease.
AB  - OBJECTIVE: Sulforaphane is an activator of transcription factor NF-E2-related
      factor-2 (nrf2) that regulates gene expression through the promoter antioxidant
      response element (ARE). Nrf2 regulates the transcription of a battery of
      protective and metabolic enzymes. The aim of this study was to assess whether
      activation of nrf2 by sulforaphane in human microvascular endothelial cells
      prevents metabolic dysfunction in hyperglycemia. RESEARCH DESIGN AND METHODS:
      Human microvascular HMEC-1 endothelial cells were incubated in low and high
      glucose concentrations (5 and 30 mmol/l, respectively), and activation of nrf2
      was assessed by nuclear translocation. The effects of sulforaphane on multiple
      pathways of biochemical dysfunction, increased reactive oxygen species (ROS)
      formation, hexosamine pathway, protein kinase C (PKC) pathway, and increased
      formation of methylglyoxal were assessed. RESULTS: Activation of nrf2 by
      sulforaphane induced nuclear translocation of nrf2 and increased ARE-linked gene
      expression, for example, three- to fivefold increased expression of transketolase
      and glutathione reductase. Hyperglycemia increased the formation of ROS-an effect
      linked to mitochondrial dysfunction and prevented by sulforaphane. ROS formation
      was increased further by knockdown of nrf2 and transketolase expression. This
      also abolished the counteracting effect of sulforaphane, suggesting mediation by
      nrf2 and related increase of transketolase expression. Sulforaphane also
      prevented hyperglycemia-induced activation of the hexosamine and PKC pathways and
      prevented increased cellular accumulation and excretion of the glycating agent
      methylglyoxal. CONCLUSIONS: We conclude that activation of nrf2 may prevent
      biochemical dysfunction and related functional responses of endothelial cells
      induced by hyperglycemia in which increased expression of transketolase has a
      pivotal role.

PMID- 18633118
TI  - Citrus chlorophyllase dynamics at ethylene-induced fruit color-break: a study of
      chlorophyllase expression, posttranslational processing kinetics, and in situ
      intracellular localization.
AB  - Fruit color-break is the visual manifestation of the developmentally regulated
      transition of chloroplasts to chromoplasts during fruit ripening and often
      involves biosynthesis of copious amounts of carotenoids concomitant with massive
      breakdown of chlorophyll. Regulation of chlorophyll breakdown at different
      physiological and developmental stages of the plant life cycle, particularly at
      fruit color-break, is still not well understood. Here, we present the dynamics of
      native chlorophyllase (Chlase) and chlorophyll breakdown in lemon (Citrus limon)
      fruit during ethylene-induced color-break. We show, using in situ
      immunofluorescence on ethylene-treated fruit peel (flavedo) tissue, that citrus
      Chlase is located in the plastid, in contrast to recent reports suggesting
      cytoplasmic localization of Arabidopsis (Arabidopsis thaliana) Chlases. At the
      intra-organellar level, Chlase signal was found to overlap mostly with
      chlorophyll fluorescence, suggesting association of most of the Chlase protein
      with the photosynthetic membranes. Confocal microscopy analysis showed that the
      kinetics of chlorophyll breakdown was not uniform in the flavedo cells.
      Chlorophyll quantity at the cellular level was negatively correlated with plastid
      Chlase accumulation; plastids with reduced chlorophyll content were found by in
      situ immunofluorescence to contain significant levels of Chlase, while plastids
      containing still-intact chlorophyll lacked any Chlase signal. Immunoblot and
      protein-mass spectrometry analyses were used to demonstrate that citrus Chlase
      initially accumulates as an approximately 35-kD precursor, which is subsequently
      N-terminally processed to approximately 33-kD mature forms by cleavage at either
      of three consecutive amino acid positions. Chlase plastid localization,
      expression kinetics, and the negative correlation with chlorophyll levels support
      the central role of the enzyme in chlorophyll breakdown during citrus fruit color
      break.

PMID- 18633120
TI  - Expression of Umbelopsis ramanniana DGAT2A in seed increases oil in soybean.
AB  - Oilseeds are the main source of lipids used in both food and biofuels. The
      growing demand for vegetable oil has focused research toward increasing the
      amount of this valuable component in oilseed crops. Globally, soybean (Glycine
      max) is one of the most important oilseed crops grown, contributing about 30% of
      the vegetable oil used for food, feed, and industrial applications. Breeding
      efforts in soy have shown that multiple loci contribute to the final content of
      oil and protein stored in seeds. Genetically, the levels of these two storage
      products appear to be inversely correlated with an increase in oil coming at the
      expense of protein and vice versa. One way to overcome the linkage between oil
      and protein is to introduce a transgene that can specifically modulate one
      pathway without disrupting the other. We describe the first, to our knowledge,
      transgenic soy crop with increased oil that shows no major impact on protein
      content or yield. This was achieved by expressing a codon-optimized version of a
      diacylglycerol acyltransferase 2A from the soil fungus Umbelopsis (formerly
      Mortierella) ramanniana in soybean seed during development, resulting in an
      absolute increase in oil of 1.5% (by weight) in the mature seed.

PMID- 18633119
TI  - Quantitative proteomics of a chloroplast SRP54 sorting mutant and its genetic
      interactions with CLPC1 in Arabidopsis.
AB  - cpSRP54 (for chloroplast SIGNAL RECOGNITION PARTICLE54) is involved in
      cotranslational and posttranslational sorting of thylakoid proteins. The
      Arabidopsis (Arabidopsis thaliana) cpSRP54 null mutant, ffc1-2, is pale green
      with delayed development. Western-blot analysis of individual leaves showed that
      the SRP sorting pathway, but not the SecY/E translocon, was strongly down
      regulated with progressive leaf development in both wild-type and ffc1-2 plants.
      To further understand the impact of cpSRP54 deletion, a quantitative comparison
      of ffc2-1 was carried out for total leaf proteomes of young seedlings and for
      chloroplast proteomes of fully developed leaves using stable isotope labeling
      (isobaric stable isotope labeling and isotope-coded affinity tags) and two
      dimensional gels. This showed that cpSRP54 deletion led to a change in light
      harvesting complex composition, an increase of PsbS, and a decreased photosystem
      I/II ratio. Moreover, the cpSRP54 deletion led in young leaves to up-regulation
      of thylakoid proteases and stromal chaperones, including ClpC. In contrast, the
      stromal protein homeostasis machinery returned to wild-type levels in mature
      leaves, consistent with the developmental down-regulation of the SRP pathway. A
      differential response between young and mature leaves was also found in carbon
      metabolism, with an up-regulation of the Calvin cycle and the photorespiratory
      pathway in peroxisomes and mitochondria in young leaves but not in old leaves.
      The Calvin cycle was down-regulated in mature leaves to adjust to the reduced
      capacity of the light reaction, while reactive oxygen species defense proteins
      were up-regulated. The significance of ClpC up-regulation was confirmed through
      the generation of an ffc2-1 clpc1 double mutant. This mutant was seedling lethal
      under autotrophic conditions but could be partially rescued under heterotrophic
      conditions.

PMID- 18633121
TI  - A novel ARID DNA-binding protein interacts with SymRK and is expressed during
      early nodule development in Lotus japonicus.
AB  - During the establishment of symbiosis in legume roots, the rhizobial Nod factor
      signal is perceived by the host cells via receptor-like kinases, including SymRK.
      The NODULE INCEPTION (NIN) gene in Lotus japonicus is required for rhizobial
      entry into root cells and for nodule organogenesis. We describe here a novel DNA
      binding protein from L. japonicus, referred to as SIP1, because it was identified
      as a SymRK-interacting protein. SIP1 contains a conserved AT-rich interaction
      domain (ARID) and represents a unique member of the ARID-containing proteins in
      plants. The C terminus of SIP1 was found to be responsible for its interaction
      with the kinase domain of SymRK and for homodimerization in the absence of DNA.
      SIP1 specifically binds to the promoter of LjNIN but not to that of LjCBP1 (a
      calcium-binding protein gene), both of which are known to be inducible by Nod
      factors. SIP1 recognizes two of the three AT-rich domains present in the NIN gene
      promoter. Deletion of one of the AT-rich domains at the NIN promoter diminishes
      the binding of SIP1 to the NIN promoter. The protein is localized to the nuclei
      when expressed as a red fluorescence fusion protein in the onion (Allium cepa)
      epidermal cells. The SIP1 gene is expressed constitutively in the uninfected
      roots, and its expression levels are elevated after infection by Mesorhizobium
      loti. It is proposed that SIP1 may be required for the expression of NIN and
      involved in the initial communications between the rhizobia and the host root
      cells.

PMID- 18633122
TI  - Eukaryotic translation initiation factor 5A is involved in pathogen-induced cell
      death and development of disease symptoms in Arabidopsis.
AB  - Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein
      found in all eukaryotic kingdoms. This study demonstrates that plant eIF5A is
      involved in the development of disease symptoms induced by a common necrotrophic
      bacterial phytopathogen. Specifically, AteIF5A-2, one of the three eIF5A genes in
      Arabidopsis (Arabidopsis thaliana), is shown to regulate programmed cell death
      caused by infection with virulent Pseudomonas syringae pv tomato DC3000 (Pst
      DC3000). Transgenic Arabidopsis plants with constitutively suppressed AteIF5A-2
      exhibited marked resistance to programmed cell death induced by virulent Pst
      DC3000, and there was a corresponding reduction in pathogen growth and
      development of disease symptoms in the plant tissue. Constitutive overexpression
      of AteIF5A-2 circumvented the apparent posttranscriptional regulation of AteIF5A
      2 protein expression characteristic of wild-type plants but did not increase
      susceptibility to virulent Pst DC3000 ingression. The transgenic plants with
      constitutive AteIF5A-2 overexpression did, however, display phenotypes consistent
      with precocious cell death. The results indicate that AteIF5A-2 is a key element
      of the signal transduction pathway resulting in plant programmed cell death.

PMID- 18633123
TI  - Pharmacokinetic-pharmacodynamic modeling of dalbavancin, a novel glycopeptide
      antibiotic.
AB  - Dalbavancin is a novel glycopeptide with a 2-dose, once-weekly dosing regimen
      that is being developed for the treatment of complicated skin and skin structure
      infections caused by gram-positive bacteria. Monte Carlo simulations were
      performed for dalbavancin using population pharmacokinetic data and minimum
      inhibitory concentrations (MICs) for clinical trial isolates. The time-dependent
      target was the maintenance of free drug concentrations above the MIC for 14 days
      (t>MIC). The concentration-dependent target was an area under the concentration
      time curve (AUC)/MIC ratio of approximately 1000 for Staphylococcus aureus and
      100 for Streptococcus sp. These targets were used to estimate susceptibility
      breakpoints for dalbavancin. For S aureus, the estimated susceptibility
      breakpoint was <or=0.5 microg/mL using AUC(14 days)/MIC and <or=1 microg/mL using
      t>MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least
      2 mug/mL. Because dalbavancin MIC(90)s for these species are well below these
      values, the analysis supports the use of once-weekly dosing regimens of
      dalbavancin in the treatment of complicated skin and skin structure infections.

PMID- 18633124
TI  - Obesity and adiposity are associated with the rate of patella cartilage volume
      loss over 2 years in adults without knee osteoarthritis.
AB  - OBJECTIVES: The aim of this study was to determine whether measures of obesity
      and adiposity are associated with the rate of patella cartilage volume loss in
      healthy adults. METHODS: 297 community-based adults aged 50-79 years with no
      clinical knee osteoarthritis were recruited at baseline (2003-4). 271 (62%
      female) subjects were re-examined at follow-up (2006-7). Measures of obesity
      (body mass index (BMI) and weight) and adiposity (fat mass and percentage fat
      mass), as well as patella cartilage volume, were determined by established
      protocols. RESULTS: Patella cartilage volume was lost at an annual rate of 1.8%
      (95% CI 1.4% to 2.1%). Increased baseline BMI, weight, fat mass and percentage
      fat mass were all associated with an increased rate of patella cartilage volume
      loss after adjustment for confounders (all p< or =0.04). The direction and
      magnitude of the effects were similar for both sexes but the number of men
      examined was considerably smaller and the associations were not statistically
      significant. There were no significant associations observed between change in
      any of the obesity and adiposity measures and the rate of patella cartilage
      volume loss. CONCLUSION: This study demonstrated that increased levels of obesity
      and adiposity are associated with an increased annual rate of patella cartilage
      volume loss in healthy adults. Weight-loss interventions that reduce body mass,
      or specifically target a reduction in fat mass, may help to reduce the rate at
      which patella cartilage volume is lost, and subsequently the risk of
      patellofemoral osteoarthritis.

PMID- 18633125
TI  - Influence of peptidylarginine deiminase type 4 genotype and shared epitope on
      clinical characteristics and autoantibody profile of rheumatoid arthritis.
AB  - BACKGROUND: Recent evidence suggests that distinction of subsets of rheumatoid
      arthritis (RA) depending on anti-cyclic citrullinated peptide antibody (anti-CCP)
      status may be helpful in distinguishing distinct aetiopathologies and in
      predicting the course of disease. HLA-DRB1 shared epitope (SE) and
      peptidylarginine deiminase type 4 (PADI4) genotype, both of which have been
      implicated in anti-CCP generation, are assumed to be associated with RA.
      OBJECTIVES: To elucidate whether PADI4 affects the clinical characteristics of
      RA, and whether it would modulate the effect of anti-CCPs on clinical course. The
      combined effect of SE and PADI4 on autoantibody profile was also analysed.
      METHODS: 373 patients with RA were studied. SE, padi4_94C>T, rheumatoid factor,
      anti-CCPs and antinuclear antibodies (ANAs) were determined. Disease severity was
      characterised by cumulative therapy intensity classified into ordinal categories
      (CTI-1 to CTI-3) and by Steinbrocker score. RESULTS: CTI was significantly
      associated with disease duration, erosive disease, disease activity score (DAS)
      28 and anti-CCPs. The association of anti-CCPs with CTI was considerably
      influenced by padi4_94C>T genotype (C/C: OR(adj) = 0.93, p(adj) = 0.92; C/T:
      OR(adj) = 2.92, p(adj) = 0.093; T/T: OR(adj) = 15.3, p(adj) = 0.002). Carriage of
      padi4_94T exhibited a significant trend towards higher Steinbrocker scores in
      univariate and multivariate analyses. An association of padi4_94C>T with ANAs was
      observed, with noteworthy differences depending on SE status (SE-: OR(adj) =
      6.20, p(adj)<0.04; SE+: OR(adj) = 0.36, p(adj) = 0.02) and significant
      heterogeneity between the two SE strata (p = 0.006). CONCLUSIONS: PADI4 genotype
      in combination with anti-CCPs and SE modulates clinical and serological
      characteristics of RA.

PMID- 18633126
TI  - Thoracoabdominal motion in ankylosing spondylitis: association with standardised
      clinical measures and response to therapy.
AB  - OBJECTIVES: To assess the relationship between thoracoabdominal motion during
      quiet breathing and standardised indices of disease severity in patients with
      ankylosing spondylitis (AS); also to evaluate whether thoracoabdominal motion
      improves after institution of biological agents in these patients. METHODS:
      Displacement of the rib cage (RC) and abdomen (Abd) during quiet breathing in the
      sitting, standing and supine position were recorded by impedance plethysmography
      in 60 patients (mean (SD) age 41 (10) years, 56 men) and 21 healthy men (mean
      (SD) 36 (7) years). x-y plots of RC versus Abd displacement during quiet
      breathing were constructed, and the angle of the slope of the RC-Abd loop was
      calculated and averaged for five consecutive breaths. In 13 patients treated with
      anti-tumour necrosis factor alpha (TNFalpha), measurements were made before and
      at 3, 6 and 12 months after the start of treatment. RESULTS: In the entire AS
      group, the angle of the slope of the RC-Abd loop correlated with Bath Ankylosing
      Spondylitis Functional Index (BASFI) in the sitting (R = -0.50, p<0.0001),
      standing (R = -0.36, p = 0.004) and supine (R = -0.47, p = 0.0001) position, but
      not with Bath Ankylosing Spondylitis Disease Activity (BASDAI), Bath Ankylosing
      Spondylitis Metrology Index (BASMI) or the modified Schober's test. In 13
      patients treated with anti-TNFalpha, the angle of the RC-Abd slope improved
      significantly (35-69% over baseline at 3 months) in all body positions and in a
      nearly parallel fashion with the improvements in standardised clinical
      measurements. CONCLUSIONS: The pattern of thoracoabdominal motion during quiet
      breathing correlates with BASFI, and its response to anti-TNFalpha treatment is
      large. This variable may be an appropriate target for evaluating potential
      usefulness in monitoring thoracic spine involvement and response to treatment in
      AS.

PMID- 18633127
TI  - A randomised controlled trial on the efficacy and tolerability with dose
      escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in
      patients with gout.
AB  - OBJECTIVES: To compare the efficacy and tolerability of allopurinol 300-600
      mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate
      concentration (sUr) < or =0.30 mmol/l (5 mg/dl). METHODS: A randomised,
      controlled, open-label, multicentre trial in gout patients with renal function
      defined as a calculated creatinine clearance > or =50 ml/min. Patients were
      treated with 300 mg allopurinol or 100 mg benzbromarone once a day (stage 1). If
      sUr < or =0.30 mmol/l was not attained after 2 months, the dose was doubled to
      allopurinol 300 mg twice a day or benzbromarone 200 mg once a day (stage 2). The
      primary end point was treatment success in either of the two stages, defined as
      clinical tolerability and attainment of biochemical target sUr. RESULTS: Sixty
      five patients were enrolled in stage 1; 36 received allopurinol and 29 received
      benzbromarone. Fifty-five patients (85%) were analysed at stage 1: the success
      rates were 8/31 (26%) and 13/25 (52%), respectively, and the difference was -0.26
      (95% CI from -0.486 to -0.005), p = 0.049. At stage 2, the success rates were
      21/27 (78%) and 18/23 (78%), respectively, and the difference was -0.005 (95% CI
      from -0.223 to 0.220), p = 1.00. Two patients stopped receiving allopurinol and
      three stopped receiving benzbromarone because of adverse drug reactions.
      CONCLUSIONS: Increasing the allopurinol dose from 300 to 600 mg/day and the
      benzbromarone dose from 100 to 200 mg/day according to the target sUr produced
      significantly higher success rates (both 78% successful in attaining sUr < or
      =0.30 mmol/l). No significant differences in treatment success between
      benzbromarone and allopurinol were found after dose escalation. TRIAL
      REGISTRATION NUMBER: ISRCTN49563848).

PMID- 18633128
TI  - Melanoma inhibitory activity, a biomarker related to chondrocyte anabolism, is
      reversibly suppressed by proinflammatory cytokines in rheumatoid arthritis.
AB  - OBJECTIVE: In mice, melanoma inhibitory activity (MIA) is a chondrocyte-specific
      molecule with similar regulation to collagen type II. As MIA is a small secreted
      protein, its value as cartilage biomarker in human inflammatory arthritis was
      assessed. METHODS: MIA tissue distribution was studied by quantitative PCR and
      immunohistochemistry. The regulation of MIA production was studied in vivo in
      rheumatoid arthritis (RA) (n = 37) and spondyloarthritis (SpA) (n = 30) synovial
      fluid (SF), and in vitro in alginate embedded human chondrocytes. Therapeutic
      modulation of serum MIA was evaluated during tumour necrosis factor (TNF)alpha
      and interleukin (IL)1 blockade in RA. RESULTS: MIA was primarily expressed by
      chondrocytes in the human joint. SF MIA levels were lower in RA than in SpA
      despite similar levels of overall synovial inflammation. Further analysis
      indicated that these levels were inversely correlated with the degree of joint
      inflammation in RA, but not in SpA, and that the levels of TNFalpha and IL1beta
      were significantly increased in RA versus SpA. Accordingly, these proinflammatory
      cytokines suppressed MIA mRNA and protein in cultured chondrocytes. This
      suppression was paralleled by suppression of cartilage anabolism as assessed by
      collagen type 2 and aggrecan mRNA. Treatment of patients with RA with TNF
      blockade or IL1 blockade induced an increase of serum MIA levels. CONCLUSION: The
      decreased levels of MIA in the inflamed RA joint and the coregulation of MIA and
      cartilage matrix molecules by proinflammatory cytokines indicate that joint
      inflammation in RA not only drives accelerated cartilage degradation but also
      suppresses cartilage anabolism. This inflammation-driven suppression is
      reversible in vivo.

PMID- 18633129
TI  - Dietary flavonoids inhibit the anticancer effects of the proteasome inhibitor
      bortezomib.
AB  - Dietary flavonoids have many health-promoting actions, including anticancer
      activity via proteasome inhibition. Bor-tezomib is a dipeptide boronate
      proteasome inhibitor that has activity in the treatment of multiple myeloma but
      is not effective in chronic lymphocytic leukemia (CLL). Although CLL cells are
      sensitive in vitro to bortezomib-induced apoptosis when cultured in medium, the
      killing activity was blocked when cultured in 50% fresh autologous plasma.
      Dietary flavonoids, quercetin and myricetin, which are abundant in plasma,
      inhibited bortezomib-induced apoptosis of primary CLL and malignant B-cell lines
      in a dose-dependent manner. This inhibitory effect was associated with chemical
      reactions between quercetin and the boronic acid group, -RB(OH)2, in bortezomib.
      The addition of boric acid diminished the inhibitory effect of both quercetin and
      plasma on bortezomib-induced apoptosis. The protective effect was also reduced
      when myeloma cell lines, but not B-cell lines, were preincubated with quercetin,
      indicating a direct effect of quercetin on myeloma cells. At high doses,
      quercetin itself induced tumor cell death. These data indicate that dietary
      flavonoids limit the efficacy of bortezomib, whereas supplemental inorganic boric
      acid is able to reverse this. The complex interactions between quercetin, tumor
      cells, and bortezomib mean caution is required when giving dietary advice to
      patients.

PMID- 18633130
TI  - Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the
      p53-dependent postmitotic checkpoints and synergistically induces p53-mediated
      mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous
      leukemia.
AB  - Aberrant expression of Aurora kinases and inactivation of wild-type p53 by Mdm2
      overexpression are frequent molecular events in acute myelogenous leukemia (AML),
      and preclinical data for inhibition of Aurora kinases or Mdm2 are promising.
      However, it remains largely unknown whether the viability of cells exposed to
      Aurora kinase inhibitors depends on the p53 status. We investigated the
      interaction of Aurora kinases and p53 pathways after their simultaneous blockades
      using a small-molecule pan-Aurora kinase inhibitor, MK-0457, and a selective
      small-molecule antagonist of Mdm2, Nutlin-3. We found that MK-0457, which itself
      activates p53 signaling, acts synergistically with Nutlin-3 to induce apoptosis
      in wild-type p53 AML cell lines OCI-AML-3 and MOLM-13 but not in p53-null HL-60
      cells. MK-0457 and Nutlin-3 showed synergism in inducing p53, conformational
      change of Bax and Deltapsi(m) loss, suggesting an involvement of p53-mediated
      mitochondrial apoptosis. Nutlin-3 constrained endoreduplication after Aurora
      inhibition via activation of a p53-dependent postmitotic checkpoint and p21
      induction in pseudo-G1 cells. Our findings provide the molecular rationale for
      concomitant targeting of Aurora kinases and Mdm2 in AML where TP53 mutations are
      rare and downstream p53 signaling is mostly intact.

PMID- 18633131
TI  - Host immune gene polymorphisms in combination with clinical and demographic
      factors predict late survival in diffuse large B-cell lymphoma patients in the
      pre-rituximab era.
AB  - To evaluate the hypothesis that host germ line variation in immune genes is
      associated with overall survival in diffuse large B-cell lymphoma (DLBCL), we
      genotyped 73 single nucleotide polymorphisms (SNPs) from 44 candidate genes in
      365 DLBCL patients diagnosed from 1998 to 2000. We estimated hazard ratios (HRs)
      and 95% confidence intervals (CIs) for the association of SNPs with survival
      after adjusting for clinical factors. During follow-up, 96 (26%) patients died,
      and the median follow-up was 57 months for surviving patients. The observed
      survival of this cohort was consistent with population-based estimates
      conditioned on surviving 12 months. An IL10 haplotype (global P = .03) and SNPs
      in IL8RB (rs1126580; HR(AG/GG) = 2.11; CI, 1.28-3.50), IL1A (rs1800587; HR(CT/TT)
      = 1.90; CI, 1.26-2.87), TNF (rs1800629; HR(AG/GG) = 1.44; CI, 0.95-2.18), and
      IL4R (rs2107356; HR(CC/CT) = 1.97; CI, 1.01-3.83) were the strongest predictors
      of overall survival. A risk score that combined the latter 4 SNPs with clinical
      factors was strongly associated with survival in a Cox model (P = 6.0 x 10(-11)).
      Kaplan-Meier 5-year survival estimates for low, intermediate-low, intermediate
      high, and high-risk patients were 94%, 79%, 60%, and 48%, respectively. These
      data support a role for germ line variation in immune genes, particularly genes
      associated with a proinflammatory state, as predictors of late survival in DLBCL.

PMID- 18633132
TI  - The logopenic/phonological variant of primary progressive aphasia.
AB  - OBJECTIVE: Primary progressive aphasia (PPA) is characterized by isolated decline
      in language functions. Semantic dementia and progressive nonfluent aphasia are
      accepted PPA variants. A "logopenic" variant (LPA) has also been proposed, but
      its cognitive and anatomic profile is less defined. The aim of this study was to
      establish the cognitive and anatomic features of LPA. METHODS: Six previously
      unreported LPA cases underwent extensive neuropsychological evaluation and an
      experimental study of phonological loop functions, including auditory and visual
      span tasks with digits, letters, and words. For each patient, a voxel-wise,
      automated analysis of MRI or SPECT data were conducted using SPM2. RESULTS: In
      LPA, speech rate was slow, with long word-finding pauses. Grammar and
      articulation were preserved, although phonological paraphasias could be present.
      Repetition and comprehension were impaired for sentences but preserved for single
      words, and naming was moderately affected. Investigation of phonological loop
      functions showed that patients were severely impaired in digit, letter, and word
      span tasks. Performance did not improve with pointing, was influenced by word
      length, and did not show the normal phonological similarity effect. Atrophy or
      decreased blood flow was consistently found in the posterior portion of the left
      superior and middle temporal gyri and inferior parietal lobule. CONCLUSIONS:
      Logopenic progressive aphasia (LPA) is a distinctive variant of primary
      progressive aphasia. Cognitive and neuroimaging data indicate that a deficit in
      phonological loop functions may be the core mechanism underlying the LPA clinical
      syndrome. Recent studies suggest that Alzheimer disease may be the most common
      pathology underlying the LPA clinical syndrome.

PMID- 18633133
TI  - A two-site ELISA can quantify upregulation of SMN protein by drugs for spinal
      muscular atrophy.
AB  - OBJECTIVES: Spinal muscular atrophy (SMA) is an autosomal recessive disorder
      characterized by loss of lower motor neurons during early or postnatal
      development. Severity is variable and is inversely related to the levels of
      survival of motor neurons (SMN) protein. The aim of this study was to produce a
      two-site ELISA capable of measuring both the low, basal levels of SMN protein in
      cell cultures from patients with severe SMA and small increases in these levels
      after treatment of cells with drugs. METHODS: A monoclonal antibody against
      recombinant SMN, MANSMA1, was selected for capture of SMN onto microtiter plates.
      A selected rabbit antiserum against refolded recombinant SMN was used for
      detection of the captured SMN. RESULTS: The ratio of SMN levels in control
      fibroblasts to levels in SMA fibroblasts was greater than 3.0, consistent with
      Western blot data. The limit of detection was 0.13 ng/mL and SMN could be
      measured in human NT-2 neuronal precursor cells grown in 96-well culture plates
      (3 x 10(4) cells per well). Increases in SMN levels of 50% were demonstrable by
      ELISA after 24 hours treatment of 10(5) SMA fibroblasts with valproate or
      phenylbutyrate. CONCLUSION: A rapid and specific two-site, 96-well ELISA assay,
      available in kit format, can now quantify the effects of drugs on survival of
      motor neurons protein levels in cell cultures.

PMID- 18633134
TI  - Glycoconjugate microarray based on an evanescent-field fluorescence-assisted
      detection principle for investigation of glycan-binding proteins.
AB  - The extensive involvement of glycan-binding proteins (GBPs) as regulators in
      diverse biological phenomena provides a fundamental reason to investigate their
      glycan-binding specificities. Here, we developed a glycoconjugate microarray
      based on an evanescent-field fluorescence-assisted detection principle for
      investigation of GBPs. Eighty-nine selected multivalent glycoconjugates
      comprising natural glycoproteins, neo-glycoproteins, and polyacrylamide (PAA)
      conjugated glycan epitopes were immobilized on an epoxy-activated glass slide.
      The GBP binding was monitored by an evanescent-field fluorescence-assisted
      scanner at equilibrium without washing steps. The detection principle also allows
      direct application of unpurified GBPs with the aid of specific antibodies. Model
      experiments using plant lectins (RCA120, ConA, and SNA), galectins (3 and 8), a C
      type lectin (DC-SIGN) and a siglec (CD22) provided data consistent with previous
      work within 4 h using less than 40 ng of GBPs per analysis. As an application,
      serum profiling of antiglycan antibodies (IgG and IgM) was performed with Cy3
      labeled secondary antibodies. Moreover, novel carbohydrate-binding ability was
      demonstrated for a human IL-18 binding protein. Thus, the developed glycan array
      is useful for investigation of various types of GBPs, with the added advantage of
      wash-free analysis.

PMID- 18633135
TI  - Galectin-1 signaling in leukocytes requires expression of complex-type N-glycans.
AB  - Dimeric galectin-1 (dGal-1) is a homodimeric lectin with multiple proposed
      functions. Although dGal-1 binds to diverse glycans, it is unclear whether dGal-1
      preferentially binds to specific subsets of glycans on cell surfaces to transmit
      signals. To explore this question, we selectively inhibited major glycan
      biosynthetic pathways in human HL60, Molt-4, and Jurkat cells. Inhibition of N
      glycan processing blocked surface binding of dGal-1 and prevented dGal-1-induced
      Ca(2+) mobilization and phosphatidylserine exposure. By contrast, inhibition of O
      glycan or glycosphingolipid biosynthesis did not affect dGal-1 binding or dGal-1
      induced Ca(2+) mobilization and phosphatidylserine exposure. These results
      demonstrate that dGal-1 preferentially binds to and signals through glycoproteins
      containing complex-type N-glycans in at least some leukocyte subsets.

PMID- 18633136
TI  - 11-ketotestosterone stimulates putative sex pheromone production in the male
      peacock blenny, Salaria pavo (Risso 1810).
AB  - Male peacock blennies (Salaria pavo) release odors from their anal glands and,
      possibly, from their gonads that attract reproductive females. The current study
      investigated the effects of 11-ketotestosterone (KT) on development of the anal
      glands, testes, and accessory testicular organs as well as the subsequent
      olfactory potency of their secretions. After 3 wk of KT treatment (5 mg/kg in
      silastic implants), clusters of cells secreting neutral mucins differentiated in
      the anal gland of all treated males, whereas this occurred in only one control
      male. Secretions by anal glands from KT-treated males elicited greater olfactory
      responses, as assessed by electro-olfactography, than those from controls.
      Treatment with KT stimulated testicular gland growth and sialomucin secretion but
      had no clear effect on the germinal region of the testis; KT also stimulated
      enlargement of, and fluid secretion in, the blind pouches (paired evaginations of
      the spermatic ducts). Secretions by the testes and fluid in blind pouches from KT
      treated males elicited greater olfactory responses than those from controls. In
      conclusion, KT stimulates development of the anal glands and testicular accessory
      organs and promotes odorant secretion, the putative multicomponent male peacock
      blenny pheromone.

PMID- 18633137
TI  - A phenotypic spectrum of sexual development in Dax1 (Nr0b1)-deficient mice:
      consequence of the C57BL/6J strain on sex determination.
AB  - Nuclear receptor subfamily 0, group B, member 1 (Nr0b1; hereafter referred to as
      Dax1) is an orphan nuclear receptor that regulates adrenal and gonadal
      development. Dosage-sensitive sex reversal, adrenal hypoplasia congenita,
      critical region on the X chromosome, gene 1 (Dax1) mutations in the mouse are
      sensitive to genetic background. In this report, a spectrum of impaired gonadal
      differentiation was observed as a result of crossing the Dax1 knockout on the
      129SvIm/J strain onto the C57BL/6J strain over two generations of breeding. Dax1
      mutant XY mice of a mixed genetic background (129;B6Dax1(-/Y) [101 total])
      developed gonads that were predominantly testislike (n = 61), ovarianlike (n =
      27), or as intersex (n = 13). During embryonic development, Sox9 expression in
      the gonads of 129;B6Dax1(-/Y) mutants was distributed across a wide quantitative
      range, and a threshold level of Sox9 (>0.4-fold of wild-type) was associated with
      testis development. Germ cell fate also varied widely, with meiotic germ cells
      being more prevalent in the ovarianlike regions of embryonic gonads, but also
      observed within testicular tissue. Ptgds, a gene associated with Sox9 expression
      and Sertoli cell development, was markedly downregulated in Dax1(-/Y) mice.
      Stra8, a gene associated with germ cell meiosis, was upregulated in Dax1(-/Y)
      mice. In both cases, the changes in gene expression also occurred in pure 129
      mice but were amplified in the B6 genetic background. Sertoli cell apoptosis was
      prevalent in 129;B6Dax1(-/Y) gonads. In summary, Dax1 deficiency on a partial B6
      genetic background results in further modulation of gene expression changes that
      affect both Sertoli cell and germ cell fate, leading to a phenotypic spectrum of
      gonadal differentiation.

PMID- 18633138
TI  - Fetomaternal trafficking in the mouse increases as delivery approaches and is
      highest in the maternal lung.
AB  - The purpose of the study was to understand in more detail the natural history of
      fetomaternal cell trafficking in healthy pregnant mice. Our goal was to identify
      the best target organs and days during pregnancy for further mechanistic studies
      of the role of fetal cells in maternal disease and injury. C57BL/6J wild-type
      virgin females (n = 54) were mated with congenic enhanced green fluorescent
      protein (EGFP) transgenic males. During pregnancy and after delivery, female mice
      were euthanized, and eight organs and blood were analyzed for the presence of
      fetal GFP+ cells with flow cytometry and real-time quantitative PCR. Maternal
      lungs, liver, and spleen were also analyzed by fluorescent stereomicroscopy.
      Fetal GFP+ cells were first found at low frequency at Embryonic Day 11, increased
      to a maximum at Embryonic Day 19, and decreased rapidly postpartum. These fetal
      cell dynamics were significantly reproducible among all mice studied. In
      addition, there was a consistent distribution of fetal cells within maternal
      organs, with lung, liver, blood, and spleen having the greatest concentrations;
      these were highly correlated at all time points (P < 0.0001). Maternal lung
      contained 10- to 100-fold more fetal cells than any other organ, and using all
      three techniques, the number of fetal cells detected was the most consistent and
      reproducible in this organ. Stereomicroscopy showed that within the lung, fetal
      cells were widely and apparently randomly distributed. Using a murine model, our
      data demonstrate that fetomaternal cellular trafficking occurs in reproducible
      patterns, is maximal near term delivery, and has predilection for the maternal
      lung.

PMID- 18633139
TI  - CDC25B acts as a potential target of PRKACA in fertilized mouse eggs.
AB  - Protein kinase A (PRKACA) has been documented as a pivotal regulator in meiosis
      and mitosis arrest. Although our previous work has established that PRKACA
      regulates cell cycle progression of mouse fertilized eggs by inhibiting M-phase
      promoting factor (MPF), little is known about the intermediate factor between
      PRKACA and MPF in the mitotic cell cycle. In this study, we investigated the role
      of the PRKACA/CDC25B pathway on the early development of mouse fertilized eggs.
      Overexpression of unphosphorylatable CDC25B mutant (Cdc25b-S321A or Cdc25b
      S229A/S321A) rapidly caused G2-phase eggs to enter mitosis. Microinjection of
      either Cdc25b-WT or Cdc25b-S229A mRNA also promoted G2/M transition, but much
      less efficiently than Cdc25b-S321A and Cdc25b-S229A/S321A. Moreover, mouse
      fertilized eggs overrode the G2 arrest by microinjection of either Cdc25b-S321A
      or Cdc25b-S229A/S321A mRNA, which efficiently resulted in MPF activation by
      directly dephosphorylating CDC2A-Tyr15, despite culture under conditions that
      maintained exogenous dibutyryl cAMP. Using a highly specific antibody against
      phospho-Ser321 of CDC25B in Western blotting, we showed that CDC25B-Ser321 was
      phosphorylated at the G1 and S phases, whereas Ser321 was dephosphorylated at the
      G2 and M phases in vivo. Our findings identify CDC25B as a potential target of
      PRKACA and show that PRKACA regulates G2/M transition by phosphorylating CDC25B
      Ser321 but not CDC25B-Ser229 on the first mitotic division of mouse fertilized
      eggs.

PMID- 18633140
TI  - The proregion of mouse BMP15 regulates the cooperative interactions of BMP15 and
      GDF9.
AB  - Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9
      (GDF9) are secreted by the mammalian oocyte and are essential for ovarian
      follicular development, ovulation, and fertility. However, the secreted forms of
      the BMP15 and GDF9 proteins and the nature of cooperative molecular interactions
      between BMP15 and GDF9 previously reported have not been fully characterized. In
      this study, we found that recombinant mouse BMP15 and GDF9 are secreted as
      cleaved mature and proregion proteins, with BMP15 also secreted as uncleaved
      promature protein. Noncovalent interactions were identified between the mature
      and proregion proteins of each growth factor. Moreover, GDF9 mature protein was
      found to coimmunoprecipitate with the BMP15 proregion, suggestive of a
      heteromeric association between BMP15 and GDF9. Mouse GDF9 was found to exist
      mostly as a dimer of mature protein, in both the presence and absence of BMP15.
      In contrast, BMP15 formed mostly multimers of proregion and mature protein when
      combined with GDF9, providing further evidence for heteromeric interaction. Mouse
      BMP15 was found to act cooperatively with GDF9 in a rat granulosa cell thymidine
      incorporation bioassay and to signal through the BMPR2 and ACVR1B/TGFBR1/ACVR1C
      receptor-mediated pathways. Immunoneutralization experiments using GDF9 mature
      protein antibody indicated that these cooperative interactions are species
      specific. Additionally, immunoneutralization with proregion antibodies
      highlighted the involvement of the BMP15 proregion in BMP15/GDF9 cooperative
      interactions. Taken together, these findings support a novel hypothesis where the
      extracellular cooperative interactions of recombinant mouse BMP15 and GDF9 are
      multimeric, involving the proregion of BMP15, and may well be species specific.

PMID- 18633141
TI  - Dicer1 is required for differentiation of the mouse male germline.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate
      gene expression. Hundreds of miRNAs are expressed in mammals; however, their
      functions are just starting to be uncovered. MicroRNAs are processed from a long
      hairpin mRNA transcript, down to a approximately 23-nucleotide duplex. The enzyme
      Dicer1 is required for miRNA processing, and mouse knockouts of Dicer1 are
      embryonic lethal before 7.5 days postcoitus. To examine the function of miRNAs
      specifically in the germline, we used a mouse model that expresses Cre
      recombinase from the TNAP locus and a floxed Dicer1 conditional allele. Removal
      of Dicer1 from germ cells resulted in male infertility. Germ cells were present
      in adult testes, but few tubules contained elongating spermatids. Germ cells that
      did differentiate to elongating spermatids exhibited abnormal morphology and
      motility. Rarely, sperm lacking Dicer1 could fertilize wild-type eggs to generate
      viable offspring. These results show that Dicer1 and miRNAs are essential for
      proper differentiation of the male germline.

PMID- 18633143
TI  - [Anesthesia management during the total hip replacement surgery].
AB  - Comparative analysis of two methods of anesthesia has been performed to determine
      the optimal method of anesthesia for total hip replacement. It was revealed that
      suggested methods - both general (GA) and combined (GA with epidural anesthesia -
      EA) provide an adequate anesthesia and allow patients with stable hemodynamics
      and respiratory metabolism undergo various types of major traumatic operations
      such as THR. Compared with GA, combined multicomponent (GA and EA) has reduced
      using Propofol by 50% and Fentanyl by 56%. Data from our trials have also showed
      that combined anesthesia slightly decreased intraoperative blood loss by 10% and
      there is no evident advantage of using above-mentioned method of anesthesia for
      this purpose.

PMID- 18633142
TI  - Efficient term development of vitrified ferret embryos using a novel pipette
      chamber technique.
AB  - Development of an efficient cryopreservation technique for the domestic ferret is
      key for the long-term maintenance of valuable genetic specimens of this species
      and for the conservation of related endangered species. Unfortunately, current
      cryopreservation procedures, such as slow-rate freezing and vitrification with
      open pulled straws, are inefficient. In this report, we describe a pipette tip
      based vitrification method that significantly improves the development of thawed
      ferret embryos following embryo transfer (ET). Ferret embryos at the morula (MR),
      compact morula (CM), and early blastocyst (EB) stages were vitrified using an
      Eppendorf microloader pipette tip as the chamber vessel. The rate of in vitro
      development was significantly (P < 0.05) higher among embryos vitrified at the CM
      (93.6%) and EB (100%) stages relative to those vitrified at the MR stages
      (58.7%). No significant developmental differences were observed when comparing CM
      and EB vitrified embryos with nonvitrified control CM (100%) and EB (100%)
      embryos. In addition, few differences in the ultrastructure of intracellular
      lipid droplets or in microfilament structure were observed between control
      embryos and embryos vitrified at any developmental stage. Vitrified-thawed CM/EB
      embryos cultured for 2 or 16 h before ET resulted in live birth rates of 71.3%
      and 77.4%, respectively. These rates were not significantly different from the
      control live birth rate (79.2%). However, culture for 32 h (25%) or 48 h (7.8%)
      after vitrification significantly reduced the rate of live births. These data
      indicate that the pipette chamber vitrification technique significantly improves
      the live birth rate of transferred ferret embryos relative to current state-of
      the-art methods.

PMID- 18633144
TI  - [Hemodynamics and gas exchange during spine operations in the prone position].
AB  - Hemodynamics and respiratory metabolism of 30 patients in the prone position
      spine surgery under GA have been studied and analyzed. Results showed that there
      were no evident hemodynamic changes in patients without any risk of developing
      cardiovascular complications (ASA I-II). Posture effect of the circulation during
      anesthesia and spine operation was not marked. Data from our trials did not
      reveal any deterioration in gas exchange and acid-base balance in patients
      undergoing surgery in this position (ASA I-II) during adequate artificial
      respiration lasting 2 hours.

PMID- 18633145
TI  - Dopplerography in the diagnosis of preeclampsia in the second trimester of
      pregnancy.
AB  - Preeclampsia - a multisystem disorder characterized by hypertension and
      proteinuria that occurs more frequently. The disease is one of the most important
      causes of maternal and fetal mortality and morbidity in developed countries. The
      aim of the research was to estimate the value of screening for preeclampsia and
      fetal growth restriction by performing Doppler assessment of uterine arteries for
      revealing the circulatory disturbances in uterine arteries in predicting adverse
      pregnancy outcome. The dopplerography of 38 pregnant women; among them 10 - with
      severe preeclampsia, 13 - with mild preeclapmsia and 15 - control women groups
      (physiological pregnancy) was performed. According to the obtained data,
      dopplerography demonstrated high information value and reliability to identify
      women at risk of developing the disorder early enough in their pregnancies to
      permit preventive treatment.

PMID- 18633146
TI  - Relationship of 24-hour blood pressure rhythm with endothelial function and blood
      rheology.
AB  - The purpose of the study was to investigate relationships between sex, blood
      pressure level, duration of arterial hypertension (AH), 24-hour blood pressure
      (BP) rhythm, endothelial function (EF) and blood rheological parameters. 23 (mean
      age 50+/-8.73) outpatients with AH were included in the study. All subjects
      underwent off-therapy 24-hour ambulatory BP monitoring, investigation of blood
      rheological parameters and high resolution vascular dopplerography Dipper
      patients showed lower rate of platelet aggregation and platelet adhesion, than it
      was in non-dippers (86.42+/-8.20 vs. 99.36+/-5.93; P=0.0018 and 24.2+/-11.54 vs.
      42.16+/-13.71; P=0.01). Viscosity was higher in patients with endothelial
      dysfunction, than it was in patients without it (0.064+/-0.01 vs. 0.051+/-0.0035;
      P=0.004). Compared with dippers, non-dippers showed an impaired EF (11.4+/-2% vs.
      3.5+/-2.6%; p= 0.0006). The present data suggest the presence of disturbed
      endothelium-dependent vasodilatation and alterations in rheological indices in
      AH. According to the results obtained, the main factor, which leads to
      endothelial dysfunction and increase in platelet aggregative and adhesive
      activity, is the shortage in the lowering BP during the night. Consequently,
      hypertensive patients with non-dipper circadian blood pressure profile have to be
      assessed as a high risk group for development of future cardiovascular and
      cerebrovascular complications.

PMID- 18633147
TI  - Antibacterial therapy of acute infectious exacerbation of chronic obstructive
      pulmonary disease.
AB  - This article reviews the role of antibiotic therapy in the management of patients
      with acute infectious exacerbation of chronic obstructive pulmonary disease
      (COPD). Papers relevant to the issue are included in the review. Current
      antibiotic therapy of acute infectious exacerbation of COPD is directed at the
      most common pathogens, including Streptococcus pneumoniae, Haemophilus influenzae
      and Moraxella catarrhalis. Mild to moderate exacerbations of COPD are usually
      treated with broad-spectrum antibiotics such as doxycycline, trimethoprim
      sulfamethoxazole and amoxicillin-clavulanate potassium. Treatment with augmented
      penicillins, fluoroquinolones, third-generation cephalosporins or aminoglycosides
      may be considered in patients with more severe exacerbations.

PMID- 18633148
TI  - [Heart rhythm abnormalities in middle-aged veteran elite athletes].
AB  - Disrrhythmia is frequent finding in high competitive athletes. Majority of heart
      rhythm abnormalities in athletes, suggested being benign, however, prognostic
      value of it is not yet well established. Purpose of the present study was to
      investigate heart rhythm and relationship of heart rhythm abnormalities with LV
      mass in veteran elite athletes. 30 veteran elite athletes (16 soccer players and
      14 water-polo players) aged 30-50 were studied. They formed main group. INCLUSION
      CRITERIA: >10 years of active sports activity and >5 years after competitive
      sports cessation. All athletes were symptom free. Control group consists of 30
      age - matched sedentary healthy individuals. In all study subjects ambulatory 24
      hour ECG was recorded and, LV mass, dimensions and function by ultrasound-Doppler
      technique was evaluated. LV mass by Devereux formula was calculated and indexed
      to body surface area. Student's t-test for continuous variables, Descriptive
      statistics and Fisher's exact test for categorical variables were used. A P-value
      of <0.05 was considered to be statistically significant. Mean heart rate in
      former athletes group was 62+/-6 ,and 69+/-9, in control group. Night HR in
      athletes group was 48+/-8 and 55+/-5 in control group. Differences between groups
      were statistically significant (p<0,01). Complex arrhythmias were found in 4
      athletes and none in control group First degree AV block presented in 6 athletes
      and in 2 controls. Second degree AV block (Mobitz II) was found in 4 athletes and
      none in controls. LV mass index was higher in ex-athletes (91,42 g/m, than in
      controls (84,02 g/m ) .differences between groups was statistically significant -
      p<0,05. Profound Bradycardia and heart conductivity abnormalities as well as
      complex arrhythmias were more frequent findings in athletes as compared with
      healthy sedentary subjects. Heart Rhythm abnormalities were associated with
      enhanced LV mass in Veteran athletes. Hence, veteran elite athletes may be at
      increased risk of life threatening arrhythmias. However, prognostic value of
      heart rhythm disturbances in veteran athletes has to be studied.

PMID- 18633149
TI  - The role of taste and appetite regulation in the understanding of overweight and
      obesity. Proceedings of the 16th Aschauer Soiree, 26th April 2008.
AB  - Overweight and obesity have developed into major illnesses in most Western
      societies and significantly contribute to the financial burden of modern public
      health systems. Almost daily, new therapeutic proposals are published in the lay
      press, and also the scientific literature has increased dramatically in recent
      years. E.g., when searching MEDLINE (1966 - May 2008 (1)), the key word "obesity"
      meanwhile appears in more than 108,000 articles. Primary focus however, is put
      upon aspects of treatment, neglecting the role of taste and appetite regulation.
      Combining keywords like "obesity + treatment" results in over 50.000 citations,
      "obesity + diet" in over 23.000, "obesity + energy + expenditure" in over 13.000
      citations (even "obesity + gastric + bypass" still evoke 2.600 citations),
      whereas "obesity + appetite + regulation" result in some 3.000, "obesity + NPY" -
      neuropeptid Y being one of the major chemical stimulators of appetite - evoke
      some 500 and "obesity + Arc + nucleus" - the arcuate nucleus being the anatomical
      centre of appetite regulation - no more than 370 scientific publications. The
      apparent scarcity of literature about taste and appetite regulation and the
      amazing lack of interest in neuronal information processing in overweight and
      obesity, has prompted the authors to brainstorm new aspects of the world-wide
      derailment of weight control.

PMID- 18633150
TI  - [Chronic virus infections in combination with tubercular process].
AB  - The objective of this study was to investigate the role of chronic viral
      infections in development of the atypical and complicated forms of tuberculosis.
      Were investigated human herpes virus-2 (HHV-2), cytomegalovirus (CMV) and
      hepatitis C virus (HCV). Chronic viral infections have been identified as a risk
      factor for developing and complicated tuberculosis. Research has been shown, that
      infection of chronic virus diseases in patients with tuberculosis is rather
      significant and in several times exceeds similar parameters in healthy persons
      (CMV: 5.8% in healthy persons and 68.5% in patients with tuberculosis; HHV-2: 39%
      in healthy persons, 92%in patients with tuberculosis; HCV: in 36.4% patients with
      tuberculosis complicated with cirrhosis). The high level of chronic virus
      diseases and/or high frequency of their activization at patients with
      tuberculosis of various forms testify to interrelation between them. Increased
      level of chronic viral infections in patients with tuberculosis explained by the
      social factors and tuberculosis-induced immunodeficiency.

PMID- 18633151
TI  - [The influence of polyvitamin complex polijen on mutagenic and cytotoxic effect
      of copper oxychloride in white mice].
AB  - The present study investigates antimutagenic and anticytotoxic effect of
      polyvitamin complex Polijen in laboratory mice. Mutation in mice was induced by
      pesticide - copper oxychloride 3Cu(OH)2 CuCl2 , which is characterizes by the
      mutagenic and cytotoxic effect. Introduction of copper oxychloride (dosage 1/2,
      1/5, 1/10 LD50) per oral to animals induces strong increase (p<0,001) of
      frequency of chromosomal aberrations (multiple fragments, lyses), genomic
      mutations (triploidy, tetraploidy), pathological mitosis (hollow metaphase, K
      mitosis, adhesion of chromosomes) and destruction of interphase nucleuses (hollow
      nucleus). Experiments showed that administration of polyvitamin complex Polijen
      decreased 2, 5 times mutagenic and cytotoxic effect of pesticide-copper
      oxychloride.

PMID- 18633152
TI  - [Morpho-functional estimation of blood-air barrier and lung surfactant in rats of
      different age].
AB  - The alveolar-capillary barrier (or membrane, or blood-air barrier) exists in the
      gas exchanging region of the lungs. The investigation of the structural
      components of blood-air barrier under the influence of different factors in the
      organism at different age is one of the clinically significant problems of
      medicine. The influence of duration barocameral hypoxia on blood-air barrier of
      the mature and old age rats was studied. The significant changes of the blood-air
      barrier components both in ontogenesis and under hyperbaric hypoxia, especially
      in old age were revealed. Research proves the significant role of blood-air
      barrier factor on the age-associated involution of respiratory system (fibrosis,
      sclerosis). The most sensitive were cytoplasmatic processes of type I
      alveolocytes. Type II alveolocytes, basic membrane and elastic fibers in
      interstitial tissue were more stabile. The investigation showed that blood-air
      barrier directly reacts on environmental factors, decreasing the partial pressure
      of oxygen in the inspired air.

PMID- 18633153
TI  - Study of resveratrol and antioxidant activity in Georgian brand red wines and a
      number of foreign red wines.
AB  - Today wine pricing is guided by content of useful substances such as resveratrol
      and catechines. Resveratrol [3,4',5-trihydroxystilbene (RESV)] is a compound
      found in the skin of red grapes and is a constituent of red wine. Clinical
      investigation demonstrated that resveratrol lowers the levels of catecholamines,
      inhibits lipid peroxidation of low-density lipoprotein; it has anti-inflammatory,
      antioxidant activity etc. In Georgia the highest concentration of resveratrol has
      been reported in wines prepared from Saperavi grapes. Resveratrol contents and
      antioxidant activity of Georgian brand red wines made from Saperavi grape variety
      and of foreign red wines available on Georgian market were assessed and compared.
      It was found that resveratrol content distinguishes foreign wines, particularly
      the French wine from the Georgian brand red wines. The research showed that
      resveratrol content is higher in non-brand Kakhetian style Saperavi (6.24 mg/ml)
      than in European or other Georgian brand wines. Proportion of trans-resveratrol
      is higher in "Saperavi" by "Badagoni" (94.5%), French wine (93.83%) and Saperavi
      by "TbilGhvino" (93.49%). Given that trans-resveratrol is characterized by higher
      biological activity and medical importance than cis-resveratrol, their proportion
      may be an important criterion to measure healing properties of wine. In terms of
      antioxidant activity, Georgian wines are like foreign wines. It is concluded that
      Georgian brand wines with few exceptions are behind the foreign wines in several
      parameters. Since polyphenolic substances define wine price through their
      positive effects on human health, more detailed studies on polyphenolic content
      of Georgian wines are needed.

PMID- 18633154
TI  - [Mechanisms of gamma-inducible death of Jurkat cells line].
AB  - Mechanisms of radio-inducible death of Jurkat cells were investigated. Human
      lymphoblastoid T-cell line Jurkat is widely established model for studying
      apoptosis mechanisms. The cell was radiated by "Teragam" (Czech Republic) by dose
      2 g during 1 minute. After radiation cells were incubated at standard conditions
      during 24 hours. After gamma radiation in cell population amount of cells in
      gaplois (apoptotic G 0) stage was increased 8,2 folds, in diplois (G 0/G1) stage 
      by 17%, in synthetic (S) stage decreased by 35% and tetraploid (G2/M) stage by
      73% in comparison to control group. It was revealed intensive production of free
      radicals of oxygen and nitric oxide and decreasing activity of antioxidant
      enzymes (superoxidismutasa, catalasa and glutathione peroxidase). Revealed
      dependence between intensification of apoptosis and radiation-induced arrest of
      cell cycle G2/M phase may be determined by excess amount of free oxygen and
      nitrogen radicals generated in Jurkat cells as a result of nondirect effects of
      low doses of gamma radiation.

PMID- 18633155
TI  - [Urgent problems of occupational diseases in Georgia in the junction of XX-XXI
      centuries].
AB  - The radical reform of health care system in Georgia after the collapse of the
      Soviet Union negatively affected the occupational medicine, environmental
      medicine, occupational health services, and preventive measures. The level of
      medical assistance to people suffering from harmful industrial factors decreased,
      which is a serious danger for the health of the workers and for the next
      generations. The aim of the article is to protect the right to means for adequate
      health and suggest effective ways for health care improvement. In order to
      reconstruct the system of Occupational and Environmental Medicine, it is
      necessary to create a network of occupational healthcare. We strongly believe
      investment in preventive health is vital to safeguard and improve the health of
      the community. The Center of Occupational Medicine and the Institute of Labor
      Medicine and Ecology with corresponding financing, educational programs for
      medical students and continuous practice of physicians in occupational medicine,
      enhancing the number of the scientific research designed to discover the early
      forms of occupational pathologies and timely prevention of the disease is vital
      to protect the right to means for adequate health, to advance the professional
      development of physicians, nurses, research scientists, and allied health
      professionals in order to diminish general and occupational diseases in Georgia.

PMID- 18633156
TI  - Characterization of STZ-Induced Type 2 Diabetes in Zucker Fatty Rats.
AB  - The Zucker fatty (ZF) rat is a disease model of obesity and metabolic syndrome,
      such as hyperlipidemia and insulin resistance, resulting from hyperphagia owing
      to the loss of function of the leptin receptor, but it rarely develops
      hyperglycemia. We examined the effects of different doses of streptozotocin
      (STZ). A low dosage of STZ (30 mg/kg body weight, i.p.) elevated blood glucose
      levels in ZF rats up to 300 mg/dl within a week, and to nearly 500 mg/dl by 5
      weeks after injection of STZ. Besides hyperglycemia, STZ-treated ZF (STZ-ZF) rats
      retained metabolic syndrome features such as hyperlipidemia and hyperinsulinemia.
      The stimulated insulin secretion in response to orally-loaded glucose disappeared
      completely in STZ-ZF rats. Although there were no significant differences in the
      morphology of pancreatic islets between vehicle-treated ZF (Cont-ZF) and STZ-ZF
      rats, the insulin content was markedly decreased in STZ-ZF rats. The hepatic gene
      expression for gluconeogenic enzymes was upregulated in STZ-ZF rats compared with
      Cont-ZF rats. Metformin lowered the blood glucose levels of STZ-ZF rats in a dose
      dependent manner. These results suggest that STZ-ZF rats are useful for studies
      of T2DM and for the evaluation of the efficacy of anti-diabetic drugs.

PMID- 18633157
TI  - Role of MAdCAM-1 and its ligand on the homing of transplanted hematopoietic cells
      in irradiated mice.
AB  - We examined the expression of VCAM-1 and MAdCAM-1 after bone marrow
      transplantation (BMT). We also examined the influence of alpha(4)beta(7) integrin
      blockade on the homing of cells to the bone marrow and spleen. The expression of
      VCAM-1 and MAdCAM-1 by endothelial cells in the spleen and bone marrow was
      examined by immunoelectron microscopy using colloidal gold and was analyzed
      semiquantitatively. To examine the role of alpha(4)beta(7) integrin in donor
      cells, a homing assay was conducted following alpha(4)beta(7) integrin blockade
      in bone marrow-derived hematopoietic cells or spleen colony cells. Immediately
      after BMT, the expression of VCAM-1 and MAdCAM1 markedly decreased, but
      expression recovered significantly between 12 and 24 h after BMT. VCAM-1
      recovered more acutely than MAdCAM-1 from 12 h onward. In the group transplanted
      with anti-alpha(4)beta(7) integrin antibody-treated bone marrow cells, the
      numbers of homing cells in the spleen and bone marrow were significantly
      decreased in an antibody dose-dependent manner. However, the number of homing
      cells was not different in either the spleen or bone marrow between anti
      alpha(4)beta(7) integrin antibody treated and untreated spleen colony cells. It
      has been reported that alpha(4)beta(1) integrin and its receptor VCAM-1 play
      major roles in the homing of hematopoietic cells to bone marrow. Our study
      indicates the importance of MAdCAM-1 and its ligand, alpha(4)beta(7) integrin, in
      the homing of bone marrow-derived hematopoietic cells, but not spleen colony
      derived cells, to both the spleen and bone marrow.

PMID- 18633158
TI  - Detection of the antibody to lymphocytic choriomeningitis virus in sera of
      laboratory rodents infected with viruses of laboratory and newly isolated strains
      by ELISA using purified recombinant nucleoprotein.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed to detect the antibody
      against lymphocytic choriomeningitis virus (LCMV) in sera of laboratory animals.
      In this ELISA system, LCMV-nucleoprotein (NP) expressed by recombinant
      baculovirus and purified with high molar urea was used as the antigen. Sera from
      laboratory animals experimentally infected with the Armstrong strain or the newly
      isolated M1 strain of LCMV were examined to detect anti-LCMV antibody by the
      ELISA system, and the reactivity was compared with that of IFA test. Regardless
      of LCMV strain, all the sera of adult mice infected with LCMV were positive with
      very high optical density (OD). Also, the sera from mice neonatally infected with
      LCMV M1 strain were positive with slightly lower OD than adult mice. In contrast,
      all the sera of uninfected mice were negative to LCMV-NP antigen. Similarly, anti
      LCMV antibodies were detected in all the sera of hamsters, mastomyses, and
      gerbils infected with the LCMV Armstrong strain. The results of the ELISA were in
      complete agreement with those of IFA, and indicate the high sensitivity and
      specificity of the ELISA system in the detection of anti-LCMV antibody. Because
      this ELISA system does not require handling infectious LCMV in the course of the
      antigen preparation and serological assay, there is no risk of contamination in
      the laboratory or nearby animal facility. In addition, by using negative control
      antigen in parallel with positive antigen in ELISA, we can exactly check the LCMV
      contamination in laboratory animals.

PMID- 18633159
TI  - Serological evidence for hepatitis e virus infection in laboratory monkeys and
      pigs in animal facilities in Japan.
AB  - In laboratory animal facilities, monkeys and pigs are used for animal
      experiments, but the details of hepatitis E virus (HEV) infection in these
      animals are unknown. The risk of infection from laboratory animals to humans has
      become a concern; therefore, much attention should be paid to the handling of
      these animals during their care and use, including surgical procedures performed
      on infected animals. In this connection, serum samples collected from 916 monkeys
      and 77 pigs kept in 23 animal facilities belonging to the Japanese Association of
      Laboratory Animal Facilities of National University Corporations (JALAN) and the
      Japanese Association of Laboratory Animal Facilities of Public and Private
      Universities (JALAP) in Japan were examined for the purpose of detecting
      antibodies to HEV and HEV RNA by using ELISA and RT-PCR, respectively. One
      hundred and seven serum samples of 916 (11.7%) monkeys were positive for anti-HEV
      IgG, and 7 and 17 serum samples of 916 (0.8% and 5.3%) monkeys were positive for
      anti-HEV IgM and IgA, respectively. Thirty-six samples from 62 (58.1%) farm pigs
      were positive for anti-HEV IgG, whereas all samples tested from miniature pigs
      were negative (0/15, 0%). Seven samples from 62 (9.1%) farm pigs and 7 samples
      from 916 (0.8%) monkeys were positive for IgM antibody, but these HEV-IgM
      antibody positive serum samples were HEV-RNA negative by RT-PCR. The IgM antibody
      positive rate (9.1%) of farm pigs was much higher than that of monkeys (0.8%).
      These results suggest the relative levels of risk of HEV infection from these
      animals to animal handlers and researchers who work with them in laboratory
      animal facilities.

PMID- 18633160
TI  - Effects of the Ih blockers CsCl and ZD7288 on inherited epilepsy in Mongolian
      gerbils.
AB  - The h current (Ih) is an inwardly mixed cationic conductance activated by
      membrane hyperpolarization. We previously demonstrated that the Ih blockers CsCl
      and ZD7288 can significantly increase the threshold of electrically induced
      paroxysmal discharge in the rabbit hippocampus. In the present study, we examined
      the effects of these Ih blockers on inherited epilepsy in Mongolian gerbils.
      Seizure-sensitive Mongolian gerbils (n=29) underwent a series of seizure
      induction tests (including gentle handling for 1-2 min and being dropped from a
      height of 50 cm) before, during and after oral administration of 10 mM CsCl or
      0.1 mM ZD7288. Their behavioral responses were classified into 3 grades
      corresponding to no seizure (score: 0), partial seizure (score: 1), and
      generalized seizure (score: 2). In the CsCl experiments (n=10), the average
      scores were 1.09 +/- 0.10 before administration, 0.82 +/- 0.10 during
      administration, and 0.96 +/- 0.10 after administration. CsCl significantly
      increased the ratio of grade 0 behavioral responses (P<0.01, compared with the
      value before administration), and decreased the ratio of grade 1 responses
      (P<0.01). In the ZD7288 experiments (n=19), the average scores were 0.99 +/- 0.07
      before administration, 0.52 +/- 0.06 (P<0.01) during administration, and 0.76 +/-
      0.07 (P<0.05) after administration. ZD7288 significantly increased the ratio of
      grade 0 behavioral responses (P<0.01), and decreased the ratio of grade 1
      responses (P<0.05) and grade 2 responses (P<0.01). We conclude that both CsCl and
      ZD7288 have an anti-epileptic effect on inherited epilepsy in Mongolian gerbils.

PMID- 18633161
TI  - Type 2 diabetes mellitus in a non-obese mouse model induced by Meg1/Grb10
      overexpression.
AB  - We assessed the possibility of C57BL/6-Tg (Meg1/Grb10)isn(Meg1 Tg) mice as a non
      obese type 2 diabetes (2DM) animal model. Meg1 Tg mice were born normal, but
      their weight did not increase as much as normal after weaning and showed about
      85% of normal size at 20 weeks of age. Body mass index of Meg1 Tg mice was also
      smaller than that of control mice. The glucose tolerance test and insulin
      tolerance test showed that Meg1 Tg mice had reduced ability to normalize the
      blood glucose level. Blood urea nitrogen (BUN) in Meg1 Tg mice (19.6 +/- 1.2
      mg/dl) was significantly lower than in controls (22.0 +/- 0.8 mg/dl), while
      plasma triglyceride, insulin, adiponectin, and resistin levels were significantly
      higher (202.0 +/- 23.4 mg/dl vs 146.3 +/- 23.4 mg/dl, 152.4 +/- 16.3 pg/ml vs
      88.1 +/- 16.9 pg/ml, 74.4 +/- 10.9 microg/ml vs 48.3 +/- 7.0 microg/ml, and 4.0
      +/- 0.2 ng/ml vs 3.6 +/- 0.2 ng/ml, respectively). Body, visceral fat weight and
      liver weights were significantly lower (19.6 +/- 0.4 g vs 24.3 +/- 0.3 g, 376.7
      +/- 29.6 mg to 507.5 +/- 23.0 mg, and 906.0 +/- 41.8 mg to 1,001.0 +/- 15.1 mg,
      respectively). Thus, hyperinsulinemia observed in Meg1 Tg mice indicates that
      their insulin signaling pathway is somehow inhibited. With high fat diet, the
      diabetes onset rate of Meg1 Tg mice increased up to 60%. These results suggest
      that Meg1 Tg mice resemble human 2DM.

PMID- 18633162
TI  - A case of fibrosarcoma on the perivertebral surface of a ferret with hind limb
      paralysis.
AB  - A 2.5 year-old female ferret had a stiff palpable mass arising from the dorsal
      surface of the thoracic (T) to lumbar (L) vertebrae with paralysis of the hind
      limbs. By myelography the dorsal and ventral lines of contrast were not observed
      in the area forwarded of L3. Grossly, the tumor encircled the dorsal vertebrae.
      Microscopically, tumor cells were proliferated intimately and were attached to
      the vertebrae surface involving surrounding fatty and connective tissues. The
      tumor consisted of fibroblastic cells with prominent cellular atypia. The
      bromodeoxyuridine (BrdU) labeling index to examine cellular kinetics was high
      (11.8%). Based on macro and micropathological features, the present tumor was
      diagnosed as periosteal fibrosarcoma arising from perivertebral connective
      tissue.

PMID- 18633163
TI  - Factors affecting full-term development of rat oocytes microinjected with fresh
      or cryopreserved round spermatids.
AB  - Factors affecting full-term development of rat oocytes after round spermatid
      injection (ROSI) were examined using fresh and cryopreserved spermatids.
      Regardless of method (DC pulses or ionomycin) and timing (before or after ROSI)
      for oocyte activation, similar percentages of oocytes injected with cryopreserved
      spermatids developed to full-term (3.0-4.8%). In contrast, no offspring were
      obtained when fresh spermatids were injected into DC-treated oocytes (0%), but a
      higher proportion of oocytes first injected with fresh spermatids and then
      activated with ionomycin developed to full-term (6.1%). In further experiment,
      oocytes activated with ionomycin were injected with frozen-thawed spermatids, and
      then treated with cycloheximide and/or trichostatin-A. Neither chemical had a
      beneficial effect on full-term development of ROSI oocytes (3.7-7.9% vs 2.5% in
      control). In conclusion, regardless of timing of oocyte activation, activation
      treatment with ionomycin is required for full-term development of rat oocytes
      injected with fresh spermatids, and the higher potential of cryopreserved
      spermatids contributing to full-term development is notable when DC pulse is
      applied for oocyte activation.

PMID- 18633164
TI  - An Efficient reproductive method for Irs2-/- mice with C57BL/6JJcl genetic
      background.
AB  - Efficient reproduction using natural mating and reproduction technology [in vitro
      fertilization (IVF) and embryo transfer (ET)] was investigated in IRS2 deficient
      mice with C57BL/6JJcl genetic background (Irs2(-/-) mice) as a typical type 2
      diabetes model. From the results using various combinations of Irs2(-/-) and
      Irs2(-/+) mice, the combination of female Irs2(-/+) x male Irs2(-/-) was found to
      be more efficient than other combinations. In applications of reproduction
      technology using IVF and ET, the combination of female Irs2(-/+) x male Irs2(-/-)
      involves the possibility of Irs2(-/-) production by repeats using female Irs2(
      /+) mice. However, reproductive continuity using this combination is difficult
      because of dependence on human technique and the cost of ET. Therefore, we
      concluded that Irs2(-/-) mice should be produced by embryo transfer using Irs2(-/
      ) mice from a colony consisting of female Irs2(-/+) x male Irs2(-/-).

PMID- 18633165
TI  - Senescence-Accelerated Mouse (SAM) strains have a spontaneous mutation in the
      Abcb1a gene.
AB  - Senescence-Accelerated Mouse (SAM) strains are used as animal models for
      gerontological research. Here, we report that the SAMR1 strain, which shows a
      high sensitivity to toxicity of the parasiticide ivermectin, has a spontaneous
      retroviral insertional mutation in the ATP-binding cassette, sub-family B
      (MDR/TAP), member 1A (Abcb1a) gene. This mutation is identical to that found in
      Crl:CF1-Abcb1a mice, which are also highly sensitive to ivermectin due to the
      mutation. The mutant Abcb1a allele was found in SAMR4, SAMR5, SAMP1, SAMP6,
      SAMP7, and SAMP9, but not in SAMP3, SAMP8, SAMP10, SAMP11, and other outbred and
      inbred strains, including 129/SvJ strains. These results impart both caution and
      promise in the use of SAM strains in studies of biological processes in which P
      glycoprotein participates.

PMID- 18633166
TI  - Quantitative analysis of the ultrasonic vocalization responses elicited in
      adjuvant-induced arthritic rats for screening analgesic drugs.
AB  - Adjuvant-induced arthritic (AIA) rats have been developed as a chronic pain model
      to evaluate the effects of analgesic drugs. The purpose of the present study was
      to examine whether there is dose-dependent inhibition of the emission of
      ultrasonic vocalization (USV) responses by analgesic drugs in AIA rats. It was
      demonstrated that morphine (1.25-5.0 mg/kg, s.c.) and ketoprofen (2.5-10.0 mg/kg,
      s.c.) dose-dependently inhibit USV responses. These results suggest that the USV
      responses elicited in AIA rats are useful for the quantitative evaluation of
      analgesic drugs.

PMID- 18633167
TI  - Blood pressure variability reduction and organ protection in hypertension
      treatment.

PMID- 18633168
TI  - Impaired cardiovascular function predicts mortality from respiratory disorders in
      the elderly.

PMID- 18633169
TI  - The study of aortic stiffness in different hypertension subtypes in dialysis
      patients.
AB  - The aim of this study was to validate whether differences in aortic stiffness are
      responsible for the differences in cardiovascular mortality among hypertension
      subtypes. Twenty hundred and fifty continuous ambulatory peritoneal dialysis
      patients were included in the present study. They were classified into four
      groups: normotensives (n=92) with systolic blood pressure (SBP) <140 mmHg and
      diastolic blood pressure (DBP) <90 mmHg; isolated systolic hypertensives (ISH,
      n=84) with SBP > or =140 mmHg and DBP <90 mmHg; isolated diastolic hypertensives
      (IDH, n=21) with SBP <140 mmHg and DBP > or =90 mmHg; and systolic-diastolic
      hypertensives (SDH, n=53) with SBP > or =140 mmHg and DBP > or =90 mmHg. Aortic
      stiffness was assessed by pulse pressure, central pressure parameters and pulse
      wave velocity. The IDH group had more male patients and a lower mean age than the
      other groups. The percentage of diabetes in the ISH group was higher than that in
      the other groups. The comparisons of aortic stiffness showed that the ISH and SDH
      groups had higher aortic stiffness than the normotension and IDH groups. The
      aortic stiffness in the ISH group was also higher than that in the SDH group, but
      there was no significant difference in aortic stiffness between the normotension
      and IDH groups. In conclusion, this study showed that aortic stiffness was
      significantly different among different hypertension subtypes, which might be an
      underlying cause of the differences in cardiovascular mortality among the
      hypertension subtypes.

PMID- 18633170
TI  - Telmisartan but not candesartan affects adiponectin expression in vivo and in
      vitro.
AB  - To examine the effects of telmisartan on peroxisome proliferator-activated
      receptor gamma activation, we compared the effects of telmisartan with those of
      candesartan on adipocytokines and glucose and lipid metabolism in vivo and in
      vitro. In vivo, 56 patients with both type 2 diabetes and hypertension were
      enrolled and randomized to receive either telmisartan (40 mg) or candesartan (8
      mg) for 3 months. Serum adiponectin, HbA1c levels, lipid profiles and blood
      pressure were recorded at the beginning and 3 months later. In vitro,
      differentiated 3T3-L1 adipocytes were treated with telmisartan, candesartan,
      pioglitazone or vehicle for 24 h, and then adiponectin mRNA and protein levels
      were measured. The results showed that most of the metabolic parameters,
      including the lipid profiles, did not change significantly during the study in
      either group. However, the changes in serum adiponectin and plasma glucose over 3
      months were significantly greater in the telmisartan group than in the
      candesartan group. In vitro, although the protein level of adiponectin was not
      significantly elevated, the mRNA expression of adiponectin was elevated 1.5-fold
      by telmisartan in 3T3-L1 adipocytes. Our findings suggest that telmisartan may
      have beneficial effects in type 2 diabetes beyond its antihypertensive effect.

PMID- 18633171
TI  - Ambulatory arterial stiffness index or pulse pressure: which correlates better
      with arterial stiffness in resistant hypertension?
AB  - The ambulatory arterial stiffness index (AASI) is a recently proposed index
      derived from 24-h ambulatory blood pressure monitoring (ABPM) for the evaluation
      of arterial stiffness. In this cross-sectional study we investigated whether AASI
      reflects arterial stiffness in patients with resistant hypertension by comparing
      AASI and ambulatory pulse pressure (PP) with aortic pulse wave velocity (PWV), a
      measure of arterial stiffness, in 391 resistant hypertensives. Clinical,
      laboratory and echocardiographic variables, 24-h ABPM and aortic PWV (measured
      using the Complior device) were obtained. AASI was calculated as 1--the
      regression slope of 24-h diastolic on systolic blood pressure (BP). Statistical
      analysis involved single and multiple linear regressions to assess the
      correlations between the two ABPM variables and PWV, both unadjusted and adjusted
      for potential confounders (age, gender, body height, presence of diabetes, 24-h
      mean arterial pressure [MAP], heart rate, and nocturnal BP reduction). Ambulatory
      PP and aortic PWV were independently associated with age, gender, presence of
      diabetes, and 24-h MAP, whereas AASI was associated with age, diabetes, and
      nocturnal diastolic BP reduction. PP showed stronger unadjusted (r=0.39, p<0.001)
      and adjusted (r=0.22, p<0.001) correlations with aortic PWV than AASI (r=0.12,
      p=0.032 and r= -0.04, p=0.47, respectively). In the analysis of subgroups
      stratified by gender, age, presence of atherosclerotic diseases and diabetes,
      dipping pattern, and ambulatory BP control, the superiority of PP over AASI was
      apparent in all subgroups. In conclusion, 24-h ambulatory PP was better
      correlated to arterial stiffness, as evaluated by aortic PWV, than the novel
      AASI, in patients with resistant hypertension.

PMID- 18633172
TI  - Telmisartan, an angiotensin II type 1 receptor blocker, improves coronary
      microcirculation and insulin resistance among essential hypertensive patients
      without left ventricular hypertrophy.
AB  - Hypertension and insulin resistance are associated with reduced coronary
      vasodilatory capacity, possibly caused by structural changes in the coronary
      resistance vessels. The goal of this study was to compare the effect of an
      angiotensin receptor blocker (ARB) with that of a calcium channel blocker (CCB)
      on coronary flow reserve and insulin resistance among essential hypertensive
      patients without left ventricular hypertrophy. A total of 40 consecutive
      essential hypertensive patients were randomized to daily 40 mg telmisartan or 20
      mg nifedipine coat-core treatment. Coronary flow velocity reserve (CFVR)
      measurement using transthoracic Doppler echocardiography and blood tests were
      performed before and after 12 weeks of treatment. At baseline, blood pressure,
      CFVR, and homeostasis model assessment of insulin resistance (HOMA-IR) were not
      significantly different between the two groups. At the end of the treatment
      period, the telmisartan and nifedipine groups exhibited similar declines in blood
      pressure. CFVR was improved in the telmisartan group (2.4+/-0.4 to 2.9+/-0.4;
      p<0.01), but there was no difference in the nifedipine group (2.5+/-0.3 to 2.5+/
      0.3; n.s.). HOMA-IR was improved in the telmisartan group (3.1+/-1.1 to 1.6+/
      0.7; p<0.01), but there was no difference in the nifedipine group (2.8+/-1.1 to
      2.4+/-0.7; n.s.). In conclusion, this study demonstrates that antihypertensive
      therapy with telmisartan, but not nifedipine, has a beneficial effect on coronary
      microcirculation and insulin resistance among essential hypertensive patients.

PMID- 18633173
TI  - Fasting serum free fatty acid composition, waist/hip ratio and insulin activity
      in essential hypertensive patients.
AB  - Abnormal fatty acid metabolism may play an important role in the pathogenesis of
      essential hypertension (EH). We compared fasting serum free fatty acid (FFA)
      composition between EH patients and nonhypertensive (NH) subjects, and examined
      the relationships between fasting serum FFA composition and waist/hip ratio,
      insulin activity, blood pressure, serum zinc, age, and sex in both groups. We
      conducted a cross-sectional study of 232 community-dwelling subjects aged between
      35 and 60 years: 109 EH patients and 123 NH subjects. Serum FFA was determined by
      HPLC analysis. The data were analyzed by multivariate linear stepwise regression,
      stratified analysis, and correlation analysis. In men, EH patients had lower
      C22:6/C20:5 ratios (n-3 Delta6-desaturase activity index, 7.96+/-8.81 vs. 14.5+/
      13.1, p<0.01), polyunsaturated fatty acid (PUFA), n-3 PUFA and
      polyunsaturated/saturated (P/S) ratios compared with male subjects without
      hypertension. There were no differences in women. Fasting serum FFA composition
      was significantly related to many variables, including waist/hip ratio, insulin
      sensitivity index, and serum zinc (all p<0.05 or <0.01) for all the subjects, and
      included both age- and sex-related differences (both p<0.05). Compared with NH,
      EH patients had lower levels of serum zinc (14.9+/-5.00 micromol L(-1) vs. 16.8+/
      6.38 micromol L(-1), p<0.05). We concluded that EH patients had marked alteration
      in fasting serum FFA composition, which was affected by upper body obesity,
      insulin resistance, zinc deficiency, and high dietary fat, and that the
      differences were age- and sex-related.

PMID- 18633174
TI  - Adiponectin, but not leptin or high-sensitivity C-reactive protein, is associated
      with blood pressure independently of general and abdominal adiposity.
AB  - The role of adiponectin, a marker of the metabolic syndrome, on the pathogenesis
      of hypertension in comparison with markers of adipose tissue mass (leptin) and
      inflammation (high-sensitivity C-reactive protein [hs-CRP]) remains to be
      clarified. The eligible study population consisted of 2,045 residents aged > or
      =40 years who had participated in a community-based survey and had complete data
      for serum adiponectin, leptin, and hs-CRP, and for whom homeostasis model
      assessment of insulin resistance (HOMA-IR) had been calculated from insulin and
      plasma glucose. Among all eligible participants, as well as in the subgroup of
      nondiabetic normotensives (blood pressure <140/90 mmHg and without
      antihypertensive medication), all three markers were significantly correlated
      with systolic blood pressure (negative correlation for adiponectin and positive
      correlations for leptin and hs-CRP). Among all participants, systolic blood
      pressure and the presence of hypertension were determined mainly by age, sex,
      body mass index, and waist circumference. None of the markers further contributed
      to the multivariate linear regression or logistic regression models. In contrast,
      adiponectin, but not leptin, hs-CRP, or HOMA-IR, was significantly associated
      with systolic blood pressure and the presence of pre-hypertension (blood pressure
      within 120-139/80-89 mmHg) after adjustment for age, sex, body mass index, and
      waist circumference in the nondiabetic normotensive subgroup. Similarly,
      adiponectin was independently associated with diastolic blood pressure in the
      nondiabetic normotensive subgroup but not in the whole population. In conclusion,
      adiponectin, but not leptin or hs-CRP, was independently associated with blood
      pressure in a nondiabetic normotensive subgroup.

PMID- 18633175
TI  - The effects of chronic exposure to aircraft noise on the prevalence of
      hypertension.
AB  - Exposure to environmental noise has been suggested to increase the prevalence of
      hypertension. The present study investigated whether or not chronic exposure to
      military aircraft noise is related to an increased prevalence of hypertension.
      The study population consisted of 137 subjects (mean age 60+/-14 years) who lived
      within 5 km of a helicopter airbase and 486 subjects (58+/-16 years) living
      within 5 km of a fighter-jet airbase. A control group consisted of 252 subjects
      (58+/-16 years) not exposed to aircraft noise. Overall, the subjects exposed to
      military aircraft noise had a higher prevalence of hypertension than those in the
      control group (p=0.037). However, whereas those exposed to helicopter noise had a
      higher prevalence than the control group (p=0.020), those exposed to fighter-jet
      noise did not (p=0.094). The prevalence of known hypertension in the helicopter
      group was higher than in the control group (p=0.024). The prevalence odds ratio
      for hypertension adjusted for age, gender, body mass index, current smoking,
      alcohol intake, diabetes, and regular exercise was 1.62 (95% confidence interval
      [95% CI], 1.02-2.59) for the subjects exposed to helicopter noise, and 1.23 (95%
      CI, 0.87-1.74) for those exposed to fighter-jet noise. In conclusion, the results
      of the present study suggest that chronic exposure to military aircraft noise may
      be associated with hypertension. The difference in the effects between helicopter
      and fighter-jet noise implies that different kinds of noise will have different
      influences on the prevalence of hypertension.

PMID- 18633176
TI  - The influence of wave reflection on left ventricular hypertrophy in hypertensive
      patients is modified by age and gender.
AB  - It has been established that a positive association exists between the
      augmentation index (AIx) and left ventricular mass (LVM) in hypertensives, but it
      remains unclear whether this association is affected by age or gender. The aim of
      the study was to assess the effect of age and gender on the association between
      carotid AIx and LVM in hypertensive patients. We performed arterial tonometry and
      echocardiography in 512 treated hypertensive patients who were divided into 4
      groups by gender and age (older or younger than 65 years). Correlations between
      carotid AIx and echocardiographic indices were evaluated by univariable and
      multivariable models. In females, carotid AIx increased with age up to 60 years,
      but decreased thereafter. In univariable analyses, carotid AIx was positively
      correlated with the LVM index in younger females (r=0.25, p=0.04) and males
      (r=0.48, p<0.001), but not in the older age groups. Multivariable analyses showed
      that this positive correlation in younger males remained significant (beta=0.39,
      p<0.001) after adjusting for age, body mass index, and mean arterial pressure. In
      contrast, in the older subjects, carotid AIx was negatively correlated with
      relative wall thickness in females (beta= -0.14, p=0.034) and males (beta= -0.17,
      p=0.037) independent of age and mean arterial pressure. A significant association
      between carotid AIx and LVM index was seen only in younger males. The lack of any
      such association in older hypertensives can be explained by both the plateau in
      the values of carotid AIx, and the fact that LVM increased with age.

PMID- 18633177
TI  - Microalbuminuria reduction with telmisartan in normotensive and hypertensive
      Japanese patients with type 2 diabetes: a post-hoc analysis of The Incipient to
      Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic
      Nephropathy (INNOVATION) study.
AB  - The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on
      Type 2 Diabetic Nephropathy (INNOVATION) study previously showed that treatment
      with telmisartan, an angiotensin II receptor blocker, effectively reduced the
      transition from incipient to overt nephropathy in Japanese type 2 diabetic
      patients. However, that large study included both normotensive and hypertensive
      patients. In the present post hoc analysis, we aimed to assess whether or not
      telmisartan elicits beneficial effects on the progression of microalbuminuria in
      normotensive patients. We randomized 163 microalbuminuric (urinary albumin-to
      creatinine ratio: UACR of 100 to 300 mg/g creatinine) normotensive type 2
      diabetic patients to treatment with telmisartan (40 or 80 mg once daily) or
      placebo over 52 weeks. The patients treated with either dose of telmisartan
      showed lower transition rates from microalbuminuria to overt nephropathy compared
      to the placebo group. In addition, more patients on telmisartan reverted to
      normoalbuminuria (UACR<30 mg/g creatinine): 15.5% of the 40 mg group, 19.6% of
      the 80 mg group, and 1.9% of the placebo group. In normotensive patients treated
      with telmisartan, changes in UACR were not significantly correlated with changes
      in blood pressure. Side effects did not differ among the groups. The present
      study demonstrates that telmisartan prevents the progression of microalbuminuria
      (in some cases induces remission of albuminuria) in normotensive Japanese
      patients with type 2 diabetes. Telmisartan is shown to be safe and well tolerated
      in these patients.

PMID- 18633178
TI  - Metabolic disorders predict development of hypertension in normotensive Japanese
      subjects.
AB  - Each component of the metabolic syndrome is not necessarily clustered
      coincidentally. Thus, subjects who have obesity, dyslipidemia or impaired glucose
      tolerance may be at high risk for the development of hypertension. We studied the
      predictive value of the following for the development of hypertension: obesity
      (body mass index > or =25.0 kg/m2), dyslipidemia (high-density lipoprotein
      cholesterol <40 mg/dL, triglyceride > or =150 mg/dL, or use of anti-dyslipidemic
      drugs), high normal blood pressure (130 mmHg < or = systolic <140 mmHg, or 85
      mmHg < or = diastolic <90 mmHg), and impaired glucose tolerance (fasting plasma
      glucose > or =110 mg/dL or use of anti-diabetic agents). This observational study
      included 5,785 subjects without hypertension recruited from participants in our
      health checkup program. They were followed up for 1,097+/-365 d, with the
      endpoint being the development of hypertension. During the follow-up,
      hypertension developed in 1,168 subjects (74.1 per 1,000 person-years). The
      incidence of hypertension was higher in subjects who had obesity (106.2 vs.
      67.8), dyslipidemia (96.1 vs. 69.0), high normal blood pressure (166.0 vs. 40.1),
      or impaired glucose tolerance (130.5 vs. 65.3 per 1,000 person-years) than in
      those without these disorders at baseline. The risk of hypertension was increased
      as the number of metabolic disorders in an individual increased. Multiple
      regression analysis indicated that obesity, high normal blood pressure, and
      impaired glucose tolerance remained independent predictors of the onset of
      hypertension. Thus, the presence of individual components of the metabolic
      syndrome predicts the development of hypertension. Prediction of the development
      of hypertension may lead to effective prevention of both hypertension and
      resulting cardiovascular diseases.

PMID- 18633179
TI  - Brain perfusion and cognitive function changes in hypertensive patients.
AB  - The aim of our study was to estimate brain perfusion and cognitive function (CF)
      in patients with arterial hypertension (AH) before and after hypotensive therapy.
      The study included 15 patients (mean age, 53.0+/-5.7 years) with previously
      untreated or ineffectively treated essential hypertension of the second degree.
      All patients underwent brain single photon emission computed tomography (SPECT)
      scanning with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) and
      comprehensive neuropsychological testing before and after 24 weeks of hypotensive
      therapy (angiotensin-converting enzyme [ACE] inhibitor or diuretics). The brain
      perfusion was significantly lower (15-22%) in all regions of AH patients. These
      patients showed a 25% decrease in attention and psychomotor speed as well as a
      14% decrease in mentation. Six months of hypotensive therapy led to an increase
      in brain perfusion by an average of 7-11% in all brain regions. After treatment
      these patients demonstrated an average 11-18% improvements in attention and
      psychomotor speed, as well as an average 10% improvement in abstract mentation.
      Marked signs of brain hypoperfusion and impaired CF: decrease in attention,
      slowing psychomotor speed and mentation was found in hypertensive patients even
      without focal neurological symptomatology. Twenty-four weeks of hypotensive
      treatment with ACE inhibitors or diuretics had a positive effect on cerebral
      perfusion and led to CF improvement.

PMID- 18633180
TI  - Exaggerated hypertensive response to exercise in patients with diastolic heart
      failure.
AB  - Systolic load elevation during exercise prolongs left ventricular (LV)
      relaxation, compromises filling, and raises end-diastolic pressure, leading to
      reduced exercise tolerance. The aim of this study was to test the hypothesis that
      the hypertensive response to exercise is exaggerated in patients with diastolic
      heart failure (DHF). Echocardiograms and treadmill testing were performed in
      patients with DHF (n=20) and age-matched hypertension with LV hypertrophy (HTN;
      n=20). The Minnesota Living with Heart Failure Questionnaire was used to estimate
      quality of life (QOL). There were no differences in resting blood pressure or
      echocardiographic parameters between the groups. The maximum exercise time was
      significantly shorter in the DHF group than in the HTN group (6.0+/-3.0 vs.
      12.5+/-2.5 min), and the peak systolic blood pressure during exercise was
      significantly higher in the DHF group (212+/-18 vs. 189+/-16 mmHg, p<0.05). After
      4 weeks of treatment with candesartan, an angiotensin II receptor blocker (8
      mg/d), peak systolic blood pressure during exercise decreased to 191+/-13 mmHg,
      maximum exercise time increased (10.4+/-3.0 min; p<0.05), and QOL improved in
      patients with DHF, while there was no change in patients with HTN, despite the
      similar resting blood pressure. In patients with DHF, systolic blood pressure
      markedly increased during exercise, and this was accompanied by impaired exercise
      tolerance and a decreased QOL, both of which were partly suppressed by blocking
      angiotensin II.

PMID- 18633181
TI  - Synergism of hydrochlorothiazide and nifedipine on blood pressure variability
      reduction and organ protection in spontaneously hypertensive rats.
AB  - This study was designed to investigate the effects of a hydrochlorothiazide
      nifedipine combination on blood pressure (BP), blood pressure variability (BPV),
      baroreflex sensitivity (BRS), and organ protection in spontaneously hypertensive
      rats (SHR). The doses used were 10 mg/kg/d for both hydrochlorothiazide and
      nifedipine, and 10+10 mg/kg/d for the combination of these two drugs. Drugs were
      mixed into rat chow at the aforementioned doses. SHR were treated for 4 months,
      and then BP was continuously recorded for 24 h. After the determination of BRS,
      rats were killed for organ-damage evaluation. It was found that long-term
      treatment with hydrochlorothiazide, nifedipine or both significantly decreased BP
      and BPV, enhanced BRS and conferred organ protection in SHR. The combination of
      hydrochlorothiazide and nifedipine had a significant synergistic effect on BPV
      reduction, BRS enhancement and organ protection in SHR, whereas no obvious
      synergism on BP reduction was found. Multiple-regression analysis showed that the
      decrease in left ventricular and aortic hypertrophy was most closely associated
      with the decrease in systolic BPV and the increase in BRS, and the amelioration
      of renal lesions was most closely associated with the increase in BRS. In
      conclusion, long-term treatment with a combination of hydrochlorothiazide and
      nifedipine yielded a significantly synergistic effect on BPV reduction, BRS
      restoration and organ protection in SHR. In addition to BP reduction, the
      decrease in BPV and the enhancement of BRS may have made important contributions
      to the observed organ protection.

PMID- 18633182
TI  - Cellular physiology of rat cardiac myocytes in cardiac fibrosis: in vitro
      simulation using the cardiac myocyte/cardiac non-myocyte co-culture system.
AB  - An understanding of the cellular physiology of cardiac myocytes (MCs) and non
      myocytes (NMCs) may help to explain the mechanisms underlying cardiac
      hypertrophy. Despite numerous studies using MC/NMC co-culture systems, it is
      difficult to precisely evaluate the influence of each cell type because of the
      inherent cellular heterogeneity of such a system. Here we developed a co-culture
      system using Wistar rat neonatal MCs and NMCs isolated by discontinuous Percoll
      gradient and adhesion separation methods and cultured on either side of insert
      well membranes. Co-culture of MCs and NMCs resulted in significant increases in
      [3H]-leucine incorporation by MCs, in the amount of protein synthesized by MCs,
      and in the secretion of natriuretic peptides, while the addition of MCs to NMC
      cultures significantly reduced [3H]-thymidine incorporation by NMCs.
      Interestingly, the percentage of the brain natriuretic peptide (BNP) component of
      total natriuretic peptide secreted (atrial natriuretic peptide+BNP) increased as
      the number of NMCs placed in the MC/NMC co-culture system increased. However, MCs
      did not affect production of angiotensin II (Ang II) by NMCs or secretion of
      endothelin-1 and transforming growth factor-beta1 into the MC/NMC co-culture
      system. This finding was supported by the anti-hypertrophic and anti-fibrotic
      actions of RNH6270, an active form of olmesartan, on MCs in the MC/NMC co-culture
      system and on NMCs that may synthesize Ang II in the heart. The present data
      indicate that cardiac fibrosis may not only facilitate MC hypertrophy (possibly
      through the local angiotensin system) but may also change particular
      pathophysiological properties of MCs, such as the secretory pattern of
      natriuretic peptides.

PMID- 18633183
TI  - Angiotensin II increases intrarenal transforming growth factor-beta1 in rats
      submitted to sodium overload independently of blood pressure.
AB  - Angiotensin II (Ang II) promotes sodium-retention, cell growth and fibrosis in
      addition to its classical effects on blood pressure and fluid homeostasis. In
      this study we examined whether low and non-hypertensive doses of exogenous Ang II
      could enhance the intrarenal expression of transforming growth factor-beta1 (TGF
      beta1) observed in rats submitted to sodium overload. Sprague-Dawley-rats were
      infused for 2 h with 0.1 and 5 microg kg(-1) h(-1) Ang II (Ang 0.1 and Ang 5,
      respectively) together with saline solution at four different concentrations
      (isotonic and Na 0.5 mol L(-1), Na 1.0 mol L(-1) and Na 1.5 mol L(-1)). Renal
      function and mean arterial blood pressure (BP) were measured. The renal
      distributions of TGF-beta1, alpha-smooth-muscle-actin (alpha-SMA) and nuclear
      factor-kappaB (NF-kappaB) were evaluated by immunohistochemistry. While the Ang
      0.1 groups were normotensive, the Ang 5 groups developed arterial hypertension
      progressively, and the highest blood pressure values were observed when rats were
      simultaneously infused with Na 1.5 mol L(-1). Glomerular function was not altered
      in any group. In cortical tubules, all groups infused with Ang II (0.1 and 5) and
      hypertonic saline solution (HSS) showed an increase in TGF-beta1 immunostaining
      compared to those infused with HSS alone. In medullary tubules, only the Ang 5-Na
      0.5 group showed a significant increase in TGF-beta 1 immunostaining compared to
      the Na 0.5 group. Peritubular positive staining for alpha-SMA was present in
      groups receiving Ang alone or Ang-Na, in a sodium concentration-dependent manner.
      In cortical-tubules, NF-kappaB immunostaining was significantly increased in the
      Ang groups in comparison with the control and in Ang-Na 0.5 and Ang-Na 1.0 groups
      in comparison with the Na 0.5 mol L(-1) and Na 1.5 mol L(-1) groups,
      respectively, except in the case of the Ang 0.1-Na 1.5 mol L(-1) and Ang 5-Na 1.5
      mol L(-1) groups. Moreover, Ang II and sodium overload induced additional changes
      in TGF-beta1, alpha-SMA and NF-kappaB immunostanding in glomeruli, medullary
      tubules and renal vessels. In conclusion, the interaction of Ang II with acute
      sodium overload exacerbated intrarenal TGF-beta1, alpha-SMA and NF-kappaB
      expression, independently from changes in blood pressure levels, in normal rats.

PMID- 18633184
TI  - Circulating progenitor cells after cold pressor test in hypertensive and uremic
      patients.
AB  - Endothelium was initially considered an inert lining of the blood vessels.
      Recently, it was suggested that damaged cells are continuously replaced by novel
      cells, hematopoietic stem cells (HSCs), which are directly mobilized by the bone
      marrow and then transformed into endothelial progenitor cells (EPCs). Initial
      triggers of vessel remodeling are physical forces such as blood pressure and
      fluid shear stress. We investigated whether or not a stress stimulus on vessels
      applied by a cold pressor test (CPT) would stimulate the mobilization of
      progenitor cells. Twenty-two healthy subjects, 20 patients with essential
      hypertension, and 18 with chronic kidney disease (CKD) underwent CPT by dipping
      their hands in icy water for 4 min. Immediately before and after 4 and 60 min, we
      quantified HSCs and EPCs identified by flow cytometry. We measured also adhesion
      soluble molecules (sICAM-1, sVCAM-1, and sE-selectin) as markers of endothelial
      activation. In healthy and hypertensive subjects, but not in CKD subjects, the
      number of HSCs was elevated as a direct response to CPT stress. Levels of EPCs
      and adhesion soluble molecules increased significantly, but to a different extent
      in every group. In CKD patients, the number of EPCs did not return to basal
      levels either after 60 min. Levels of adhesion soluble molecules directly
      correlated with the number of progenitor cells in hypertensive and healthy
      subjects. CPT caused an increase in adhesion soluble molecules. Discrepancies in
      the numbers of HSCs and EPCs in CKD patients could suggest a specific impairment
      in blood vessel remodeling correlated with recognized endothelial dysfunction.

PMID- 18633185
TI  - Transgenic expression of matrix metalloproteinase-1 inhibits myocardial fibrosis
      and prevents the transition to heart failure in a pressure overload mouse model.
AB  - Hypertension induces dysfunctional matrix remodeling that results in the
      development of myocardial fibrosis. Myocardial fibrosis adversely affects
      compliance, electrical activity and cardiac function in patients with
      hypertensive heart disease. Matrix metalloproteinases (MMPs) are a class of
      enzymes that regulate the remodeling of the matrix in response to pressure
      overload. Several studies have shown that the MMP-1/TIMP (tissue inhibitor of
      matrix metalloproteinase) ratio is decreased in hypertensive heart disease.
      However, the exact role that MMP-1 has in modulating the fibrotic response to
      hypertension is largely unknown. We hypothesized that cardiac expression of MMP-1
      in mice would protect against the development of dysfunctional matrix remodeling
      during pressure overload. To investigate this, a suprarenal aortic banding model
      was utilized. Banded and unbanded MMP-1 transgenic mice were compared with
      appropriately matched wild-type mice. The banded mice were examined at 2 and 5
      weeks after banding. MMP-1 attenuated the development of cardiac fibrosis,
      prevented left ventricular dilation and preserved cardiac function in mice that
      were exposed to pressure overload. Thus, MMP-1 protected the heart from the
      dysfunctional remodeling that occurs in response to chronic hypertension. In
      conclusion, these results suggest that strategies aimed at improving the MMP
      1/TIMP balance in the myocardium may help to prevent the onset and progression of
      hypertensive heart disease.

PMID- 18633186
TI  - Blockade of endogenous proinflammatory cytokines ameliorates endothelial
      dysfunction in obese Zucker rats.
AB  - To study the role of endogenous proinflammatory cytokines in endothelial
      dysfunction in diabetes, we administered semapimod, an inhibitor of
      proinflammatory cytokine production, to obese Zucker (OZ) rats, and examined its
      effect on endothelium-dependent vasorelaxation. Endothelium-dependent
      vasorelaxation induced by acetylcholine and adrenomedullin (AM) was significantly
      reduced in OZ rats compared to a control group of lean Zucker rats. Semapimod
      significantly restored endothelium-dependent vasorelaxation in OZ rats. This
      effect of semapimod was well correlated with the reduction in the serum
      concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and C
      reactive protein, as well as with the recovery of AM-induced Akt phosphorylation
      and cGMP production. Furthermore, acute administration of TNF-alpha significantly
      suppressed endothelium-dependent vasorelaxation and AM-induced cGMP production.
      These results implicate endogenous proinflammatory cytokines, especially TNF
      alpha, in endothelial dysfunction in diabetes, and indicate that blockade of
      these cytokines will be a promising strategy for inhibiting the progression of
      vascular inflammation.

PMID- 18633187
TI  - Pioglitazone enhances the antihypertensive and renoprotective effects of
      candesartan in Zucker obese rats fed a high-protein diet.
AB  - The metabolic syndrome is a risk factor for the development of chronic kidney
      disease. Angiotensin II type 1 receptor blockers (ARBs) and thiazolidinediones
      (TZDs) provide renovascular protection, probably in the metabolic syndrome.
      However, the effect of both agents administered together in patients with
      metabolic syndrome remains to be determined. The aim of this study was to assess
      the effects of ARB plus TZD combination therapy in Zucker obese rats fed a high
      protein diet, an animal model of metabolic syndrome and renal injury. Zucker
      obese rats were fed a high-protein diet (OHP; n=6), a high-protein diet
      containing candesartan, an ARB (OHP+C; n=6), or a high-protein diet containing
      both candesartan and pioglitazone (OHP+CP; n=6) for 12 weeks. Systolic blood
      pressure and urinary protein excretion were measured throughout the study, and
      renal histology and immunohistochemistry were assessed at 12 weeks. OHP rats
      developed hypertension (157+/-4 mmHg) and proteinuria (178+/-44 mg/d), and these
      conditions were significantly ameliorated by candesartan (to 143+/-3 mmHg and
      84+/-25 mg/d, respectively). Pioglitazone enhanced the antihypertensive and anti
      proteinuric effects of candesartan (121+/-3 mmHg, 16+/-8 mg/d, respectively).
      Histologically, candesartan ameliorated glomerulosclerosis, podocyte injury,
      interstitial fibrosis and monocyte/macrophage infiltration into the
      tubulointerstitium in the kidneys of OHP rats. Pioglitazone abrogated residual
      interstitial fibrosis in the kidneys of OHP+C rats. Our results suggested that
      pioglitazone augmented the antihypertensive, anti-proteinuric and possibly renal
      anti-fibrotic actions of candesartan in Zucker obese rats fed a high-protein
      diet. The combination therapy of ARB and TZD may protect against renal injury in
      patients with metabolic syndrome.

PMID- 18633188
TI  - Pioglitazone inhibits angiotensin II-induced senescence of endothelial progenitor
      cell.
AB  - We investigated whether a peroxisome proliferator-activated receptor (PPAR)
      agonist would effect the angiotensin II (Ang II)-induced senescence of
      endothelial progenitor cells (EPCs). EPCs were isolated from peripheral blood and
      characterized. Both reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blotting were used to assess gp91phox expression and angiotensin type 1
      receptor (AT1R) levels. Immunofluorescence of nitrotyrosine provided evidence of
      peroxynitrite formation. Our data indicate that Ang II increased the expression
      of gp91phox mRNA, which was significantly diminished by pioglitazone, a PPARgamma
      agonist. Western blotting revealed that Ang II stimulated an increase in the
      gp91phox protein, whereas co-treatment with pioglitazone significantly reduced
      this increase. In addition, pioglitazone also inhibited Ang II-induced
      peroxynitrite formation. Interestingly, pioglitazone decreased the expressions of
      AT1R mRNA and protein. The exposure of cultured EPCs to Ang II (100 nmol/L)
      significantly accelerated the rate of senescence compared to that of the control
      cells during 14 d in culture, as determined by acidic beta-galactosidase
      staining. Ang II-induced EPC senescence was significantly inhibited by co
      treatment with pioglitazone. Because cellular senescence is critically influenced
      by telomerase, which elongates telomeres, we also measured telomerase activity by
      means of PCR-ELISA-based assay. The results showed that Ang II significantly
      diminished telomerase activity, and this effect was significantly abolished by co
      treatment with pioglitazone. In conclusion, pioglitazone inhibited Ang II-induced
      senescence of EPCs via down-regulation of the expression of AT1R.

PMID- 18633189
TI  - Arterial stiffness, physical activity, and atrial natriuretic Peptide gene
      polymorphism in older subjects.
AB  - An increase in arterial stiffness with advancing age is associated with several
      pathological states, including hypertension and arteriosclerosis. Regular
      exercise improves the aging-induced increase in arterial stiffness and has a
      protective effect against these diseases. However, not all individuals respond to
      exercise to the same extent. Atrial natriuretic peptide (ANP) is involved in the
      regulation of basal blood pressure, blood flow, and vascular tone. The present
      study was designed to clarify whether gene polymorphisms in ANP-related genes
      affect exercise-induced improvements in arterial stiffness. We performed a cross
      sectional study of 291 healthy middle-aged and older Japanese subjects (63+/-1
      years), examining the relationship between daily physical activity-induced
      improvements in arterial stiffness, estimated by brachial-ankle arterial pulse
      wave velocity (baPWV), and the gene polymorphisms of valine32methionine (V32M:
      664G>A) in exon 1 of ANP and asparagine521aspartic acid (N521D: 1780A>G) in exon
      8 of the ANP clearance receptor (NPR-C). The baseline baPWV was significantly
      lower in the active group, but no differences were seen in blood pressure. Active
      subjects with the ANP-VV genotype had significantly lower baPWV and higher plasma
      ANP levels compared with inactive subjects, but there were no variations related
      to the VM+MM genotype. Additionally, baPWV and plasma ANP levels were negatively
      correlated in ANP-VV genotype subjects, but were not correlated in VM+MM
      individuals. Our results suggest that ANP polymorphism in older Japanese subjects
      may affect the cardiovascular response to regular exercise.

PMID- 18633190
TI  - Nighttime road-traffic noise and arterial hypertension in an urban population.
AB  - Commonly used daytime measurements in previous investigations on community noise
      and arterial hypertension (AH) may be a source of exposure bias, as urban
      residents spend most of their daytime hours out of the home on workdays. For this
      reason, we focused on the relation of nighttime noise and AH. A cross-sectional
      study was performed on a sample of 2,503 (995 men and 1,508 women) adult
      residents of a downtown Belgrade municipality. The inclusion criteria were a
      period of residence longer than 10 years and a bedroom oriented toward the
      street. The exclusion criteria were a high level of noise annoyance at work and
      diseases related to AH. Noise measurements were performed in all 70 streets of
      the municipality. The streets were grouped into noisy areas (equivalent noise
      level [Leq]>45 dB(A)) and quiet areas (Leq< or =45 dB(A)). The residents were
      interviewed in regard to antihypertensive therapy. Subjects who responded that
      they had not received such therapy were contacted for blood pressure measurements
      with mercury sphygmomanometer. Possible confounding factors: family history of
      AH, age, body mass index, smoking habits, physical activity and alcohol
      consumption were controlled for. The proportions of men with AH in the noisy and
      quiet areas were 23.6% and 17.5%, respectively. The adjusted odds ratio (OR) for
      AH was 1.58; the 95% confidence interval (CI) ranged from 1.03-2.42; and the
      probability value was 0.038, when men living in quiet streets were taken as a
      reference category. This relation was statistically insignificant for women:
      adjusted OR: 0.90; 95% CI: 0.59-1.38; p: 0.644. This cross-sectional study showed
      that nighttime urban road-traffic noise might be related to occurrence of AH in
      men.

PMID- 18633191
TI  - Ablation of the bach1 gene leads to the suppression of atherosclerosis in bach1
      and apolipoprotein E double knockout mice.
AB  - This study was designed to determine whether Bach1 gene ablation leads to
      suppression of atherosclerosis in apolipoprotein E (Apo E)/Bach1 double knockout
      (DKO) mice. Apo E/Bach1 DKO mice were generated by intercrossing Apo E knockout
      (KO) and Bach1 KO mice. The animals were fed a high-fat diet for 8 weeks, and the
      atherosclerotic plaques in the thoracic and abdominal aorta were visualized by
      oil red O staining. In DKO mice, the total plaque area was reduced by 32%
      compared with that in Apo E KO mice. In DKO mice, heme oxygenase-1 (HO-1) was
      upregulated in the endothelium and, to a lesser extent, in vascular smooth
      muscles. In atherosclerotic plaques in Apo E KO mice and DKO mice, HO-1 was
      abundantly expressed in the endothelium and macrophages. Urine excretion of 8-iso
      prostaglandin (PG) F2alpha, a marker for lipid peroxidation, was reduced in DKO
      mice compared with that in Apo E KO mice. The effects of Bach1 ablation on the
      plaque area and 8-iso-PG F2alpha excretion were almost completely abolished by
      treating DKO mice with Sn protoporphyrin, an inhibitor of HO activity. Disruption
      of the Bach1 gene in Apo E KO mice caused inhibition of atherosclerosis through
      upregulation of HO-1. Inhibition of Bach1, conversely, may be a novel therapeutic
      strategy to treat atherosclerotic diseases.

PMID- 18633192
TI  - Regression of L-NAME-induced hypertension: the role of nitric oxide and
      endothelium-derived constricting factor.
AB  - N(G)-Nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is a well
      established model of experimental hypertension. Although regression experiments
      are effective at approximating a clinical setting the reversal of already
      established L-NAME hypertension has not been intensively researched. We
      investigated whether spontaneous regression of L-NAME hypertension after
      discontinuing the drug administration was associated with recovery of endothelial
      dysfunction. Special attention was devoted to NO signaling and endothelium
      derived constricting factor (EDCF) formation in various parts of the vascular
      tree. Male adult Wistar rats were divided into 4 groups: an L-NAME (5 weeks), a
      spontaneous recovery (5 weeks L-NAME + 3 weeks of recovery) and two age-matched
      control groups (a 5- and 8-week control group). The NO-mediated and EDCF-mediated
      components of acetylcholine-induced responses were evaluated in preconstricted
      small mesenteric and femoral arteries. The activity, mRNA and protein expression
      of NO synthase together with the mRNA expression of cyclooxygenase were
      determined in the aorta. L-NAME administration caused hypertension, impaired NO
      signaling (as indicated by the reduced NO component of acetylcholine-induced
      relaxation and decreased NO synthase activity) in all arteries investigated and
      reduced the inner diameter of the femoral artery. Moreover, we observed enhanced
      cyclooxygenase-dependent EDCF formation in the femoral arteries and enhanced
      cyclooxygenase-2 expression in the aortas of L-NAME-treated rats. During
      spontaneous recovery a functional restoration of NO signaling took place in all
      parts of the vascular tree. However, the increases in systolic blood pressure,
      EDCF formation, and cyclooxygenase expression and the reduction in femoral artery
      diameter were not completely restored. We conclude that impaired NO signaling was
      improved after the cessation of L-NAME administration. However, persisting
      arterial structural alterations and enhanced EDCF formation may decelerate blood
      pressure reduction even after the restoration of NO synthase activity.

PMID- 18633193
TI  - Effects of different levels of exercise volume on endothelium-dependent
      vasodilation: roles of nitric oxide synthase and heme oxygenase.
AB  - The objective of this study was to examine the effects of moderate and high
      levels of exercise volume on endothelium-dependent vasodilation and associated
      changes in vascular endothelial/inducible nitric oxide synthase (eNOS and iNOS)
      and heme oxygenase (HO). Male Sprague-Dawley rats were assigned to sedentary
      control, acute (2 weeks), or chronic (6 weeks) treadmill running at moderate
      intensity (50% maximal aerobic velocity) with different durations of exercise
      episodes: 2 h/d (endurance training, moderate volume) and 3 h/d (intense
      training, high volume). Endothelium-dependent vascular function was examined in
      isolated thoracic aorta. Co-localization and contents of aortic eNOS/iNOS and HO
      1/HO-2 were determined with immunofluorescence and Western blotting. Compared
      with sedentary controls, rats subjected to acute and chronic endurance training
      showed enhanced endothelium-dependent relaxation (p<0.01). Whereas acetylcholine
      induced dilation was inhibited completely by NOS inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME) in sedentary controls, the dilation in the
      training groups was only partly blocked by L-NAME (inhibition was 98+/-3%, 79+/
      6%, and 77+/-5% in sedentary control, acute, and chronic training groups,
      respectively, p<0.01). The remnant dilation in the training groups was further
      inhibited by HO inhibitor protoporphyrin IX zinc, with concomitant elevation in
      aortic eNOS as well as HO-1 and HO-2. In contrast to endurance exercise, high
      volume intense training resulted in mild hypertension with significant impairment
      in endothelium-dependent vasodilation and profuse increases in aortic iNOS and
      eNOS (p<0.01). In conclusion, endothelium-dependent vasodilation is improved by
      endurance exercise but impaired by chronic intense training. Elevations of
      vascular eNOS and HO-1/HO-2 may contribute to enhanced vasodilation, which can be
      offset by intense training and elevation in vascular iNOS.

PMID- 18633194
TI  - Sleep-predominant lowering of ambulatory blood pressure by bedtime inhalation of
      a novel muscarinic M3 receptor antagonist: a new "bronchoantihypertensive"
      strategy targeting the lung in hypertension with chronic obstructive pulmonary
      disease.
AB  - Bedtime inhalation of a novel muscarinic M3 receptor antagonist markedly lowered
      ambulatory blood pressure (ABP), predominantly during sleep, in a chronic
      obstructive pulmonary disease (COPD) patient with masked nocturnal hypertension.
      This is the first case demonstrating that a bronchodilator significantly lowered
      ABP in a COPD patient with hypertension. This case suggests that bronchodilator
      therapy may have potential as a new antihypertensive strategy targeting the lung
      in hypertensive patients with impaired lung function. This
      "bronchoantihypertensive" therapy seems to be more effective for reducing sleep
      blood pressure in hypertensive patients with COPD and sleep
      hypoventilatory/hypoxemic syndromes.

PMID- 18633195
TI  - Notice of duplicate publication. Effect of nasal continuous positive airway
      pressure treatment on plasma adrenomedullin levels in patients with obstructive
      sleep apnea syndrome: roles of nocturnal hypoxia and oxidant stress.

PMID- 18633196
TI  - [Analytical method for carbamate pesticides in processed foods by LC/MS/MS].
AB  - A rapid analytical method for the simultaneous determination of carbamate
      pesticides in processed foods was established by liquid chromatography coupled
      with tandem mass spectrometry (LC/MS/MS). The pesticides were extracted from
      samples with acetonitrile using accelerated solvent extract equipment, except for
      the fine powder type spices, which were extracted in an ultrasonic bath. The
      crude extract was cleaned up with a multi-solvent GPC column (Shodex Asahipak GF
      310 HQ) using acetonitrile as a mobile phase. The eluent from the column at the
      retention time between 13 to 18 min was concentrated under nitrogen gas and
      dissolved in a mixture of acetonitrile-water-0.2 mol/L ammonium formate buffer pH
      6.0 (10 : 9 : 1). An aliquot was injected into the LC/MS/MS using electrospray
      ionization (ESI) with acquisition in the positive mode. The recoveries of 29
      kinds of pesticide from dried fruits (raisin, prune and mango) and spices
      (turmeric, masala, sage, thyme and red pepper) fortified at levels of 0.1 and
      0.01 microg/g were mostly in the range of 50 to 150% and those from soybean paste
      and soy sauce fortified at 0.01 microg/g were 46.9 to 122.6% (C.V. 3.8 to 37.6%),
      except for 4 kinds of pesticide. The determination limits (S/N> or =10)
      corresponded to 0.001 to 0.05 mug/g of the pesticides in red pepper.

PMID- 18633197
TI  - [Determination of benzylaminopurine in agricultural products].
AB  - A simplified method for the determination of benzylaminopurine in agricultural
      products by LC/MS was investigated. Benzylaminopurine in agricultural products
      was extracted with acetone and the extract was concentrated to below 30 mL.
      Buffer solution of pH 9.0 and ethyl acetate were added to the residue, and the
      solution was shaken. The ethyl acetate layer was evaporated to dryness, and the
      residue was dissolved in acetone-n-hexane (1 : 1). The solution was applied to a
      SAX/PSA mini-column, which was then rinsed with acetone-n-hexane (1 : 1).
      Benzylaminopurine was eluted with acetone-n-hexane (1 : 1) containing 1% water.
      The eluates were evaporated to dryness, and the residue was dissolved in 10
      mmol/L ammonium acetate-methanol (1 : 1). Benzylaminopurine was analyzed by
      LC/MS. The MS detection was performed in the selected ion monitoring (SIM) mode,
      with detection of the M+H(+) ion of benzylaminopurine (m/z 226) generated by
      electrospray ionization (ESI). Recoveries of benzylaminopurine from 15
      agricultural products were in the range of 83.1-97.2%. The limits of detection
      (S/N=3) of benzylaminopurine in all samples except green tea and in green tea
      were 0.0003 and 0.0012 microg/g, respectively.

PMID- 18633198
TI  - [Effects of processing and cooking on the levels of pesticide residues in rice
      samples].
AB  - The effects of processing and cooking on the levels of pesticide residues in rice
      samples were investigated for 11 pesticides in pre-harvest (9 pesticides) and
      post-harvest (4 pesticides) samples. In the polishing process, the transfer ratio
      (%, total pesticide residue amount in product/that in brown rice) of rice bran
      ranged from 40% to 106%, and the transfer ratio of polished rice ranged from 9%
      to 65% in pre-harvest samples. These values varied from pesticide to pesticide.
      The processing factor (the concentration (mg/kg) of pesticide in product/that in
      the brown rice) of polished rice ranged from 0.11 to 0.73. The loss of pesticides
      during processing and/or cooking did not correlate to any single physical or
      chemical property. Investigation of changes of pesticide residues during
      processing and/or cooking is useful not only to establish MRLs, but also to
      recognize actual levels of pesticide residues in food.

PMID- 18633199
TI  - [Effects of processing and cooking on the levels of pesticide residues in wheat
      samples].
AB  - The effects of processing and cooking on the levels of pesticide residues in
      wheat samples were investigated for 13 pesticides in pre-harvest (Pre, 9
      pesticides) and post-harvest (Post, 6 pesticides) samples. In the milling
      process, the transfer ratios (%, total pesticide residue amount in product/that
      in wheat grain) of wheat bran were greater than 70% and 80% for pre-harvest and
      post-harvest samples, respectively. The transfer ratios of flour ranged from 1.7%
      to 23% (Pre) and 4.0% to 11% (Post). There was no significant difference in
      transfer ratio among the pesticides investigated. The processing factors (Pf, the
      concentration (mg/kg) of pesticide in product/that in the wheat grain) of flour
      ranged from 0.030 to 0.40 (Pre) and 0.069 to 0.18 (Post). The values in pre
      harvest samples were higher than those in post-harvest samples. Investigation of
      changes of pesticide residues during processing and/or cooking is useful not only
      to establish MRLs, but also to recognize actual levels of pesticide residues in
      food.

PMID- 18633200
TI  - [Effects of processing and cooking on the levels of pesticide residues in soybean
      samples].
AB  - The effects of processing and cooking on the levels of pesticide residues in
      soybean samples were investigated for 14 pesticides in pre-harvest samples. On
      soaking, the transfer ratios (%, total pesticide residue amount in product/that
      in soybean) of soaked soybean were greater than 60% for most of the pesticides
      investigated. The transfer ratio of soymilk ranged from 37% to 92%, and that of
      tofu ranged from 7% to 63%. The processing factor (Pf, the concentration (mg/kg)
      of pesticide in product/that in soybean) of tofu ranged from 0.026 to 0.28. These
      values varied among pesticides. There was a high correlation between the log
      P(ow) and the transfer ratio of tofu. The test described here should be useful to
      obtain the transfer ratios of pesticide residues in processing and/or cooking
      steps.

PMID- 18633201
TI  - [Simple and rapid microbiological method for determination of residual
      antibacterials in meat].
AB  - A simple and rapid screening method using bioassay for the simultaneous analysis
      of antibacterials (penicillins, cephalosporins, macrolides, tetracyclines,
      quinolones, etc.) in meat has been developed. A 5 g sample was homogenized with 5
      mL of methanol, and the homogenate was centrifuged for 10 min with 3,000 rpm. The
      pulp disk method with Bacillus subtilis BGA (Antibiotic Medium 5 (pH 8) and 8 (pH
      6)), Micrococcus luteus ATCC 9341 and Geobacillus stearothermophilus as test
      organisms was employed for the assay of the antibacterials. Typical
      antibacterials (penicillin G, ampicillin, cefapirin, cefalexin, erythromycin,
      spiramycin, oxytetracycline, chlortetracycline, streptomycin,
      dihydrostreptomycin, enrofloxacin and oxolinic acid) were detected at levels of
      ca. 0.005-2.5 microg/g in meat. Therefore, we recommend this proposed screening
      method for routine analysis of residual antibacterials in livestock products.

PMID- 18633202
TI  - [Simultaneous determination of veterinary drugs in livestock foods and seafoods
      using liquid chromatography/tandem mass spectrometry].
AB  - A simultaneous determination of veterinary drugs in livestock food and seafood
      using liquid chromatography with tandem mass spectrometry (LC/MS/MS) was
      developed. Veterinary drugs were extracted with 95% acetonitrile. The solution
      was passed through a Florisil column, and the solvent was replaced with phosphate
      buffer. The extract was charged on a Sep-Pak Plus C(18) mini-column and divided
      into 40% methanol eluate fraction and 70% acetonitrile eluate fraction. Test
      solutions were analyzed by LC/MS/MS with gradient elution. By using this method,
      37 kinds of veterinary drugs were obtained with over 60% recovery, and
      quantitation was possible in cattle muscle, egg and fish. This method was
      inapplicable to 28 kinds of veterinary drugs. Although quantitation was not
      achieved, 42 other kinds of veterinary drugs can be screened. Since the limit of
      quantitation for this method is less than the provisional limit in general, it is
      useful as a screening method in residual analysis of veterinary drugs.

PMID- 18633203
TI  - [Simultaneous determination of aminoglycoside antibiotics in milk by liquid
      chromatography with tandem mass spectrometry].
AB  - A multiresidue method was developed for determination of nine aminoglycoside
      antibiotics (streptomycin, dihydrostreptomycin, spectinomycin, neomycin,
      kanamycin, gentamicin, destomycin A, apramycin, and tobramycin) in milk by
      LC/MS/MS. The drugs were extracted with 0.01 mol/L potassium dihydrogen phosphate
      containing 2% trichloroacetic acid, and the extracted solution was cleaned on
      cation-exchange cartridge columns (Oasis WCX and Oasis MCX). LC separation was
      performed on a TSK-gel VMpak25 column (50 mmx2.0 mm i.d.) using gradient elution
      with 0.1% formic acid and acetonitrile containing 0.1% formic acid as the mobile
      phase. Recoveries of the drugs spiked at 0.01 or 0.1 microg/g in milk ranged from
      66.1 to 110.8%, with a coefficient of variation of less than 17.1%. Limits of
      quantification of the drugs in milk were 0.001 approximately 0.01 microg/g. This
      method was used for analysis of milk from a lactating cow treated for clinical
      mastitis with two intramammary infusions of kanamycin (KM). Milk samples were
      analyzed during the withdrawal times at 12-hour intervals. KM concentrations were
      lower than the Japanese provisional MRLs (0.4 microg/g) at 60 hours after
      infusion, and subsequently fell to 0.01 microg/g.

PMID- 18633204
TI  - Analysis of trace residues of tetracyclines in dark-colored honeys by high
      performance liquid chromatography using polymeric cartridge and metal chelate
      affinity chromatography.
AB  - An efficient clean-up procedure was developed for the trace residue determination
      of tetracyclines (TCs) in dark-colored honeys. TCs were extracted from samples
      with McIlvaine buffer (pH 4.0) containing 0.01 mol/L Na(2)EDTA. The extracts were
      treated with both a polymeric cartridge (GL-Pak PLS-2) and a metal chelate
      affinity column (MCAC) preloaded with copper(II). TCs were eluted and analyzed by
      high-performance liquid chromatography (HPLC) using fluorescence detection. The
      method was evaluated for the determination of oxytetracycline (OTC), tetracycline
      (TC), and chlortetracycline (CTC) in buckwheat honey, because its color is the
      darkest. The mean recoveries of OTC, TC and CTC from spiked samples, at three
      fortification levels, were >70%, and the relative standard deviations (RSDs) were
      <10%. Limits of quantitation (LOQs) of OTC, TC, and CTC were estimated to be
      0.015 mg/kg, 0.019 mg/kg, and 0.024 mg/kg, respectively.

PMID- 18633205
TI  - [Determination of nitrofurazone in livestock products and seafoods by liquid
      chromatography-tandem mass spectrometry].
AB  - A sensitive and selective method using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) for the determination of nitrofurazone (NFZ) in swine
      muscle, swine liver, chicken muscle, chicken liver, egg, eel, yellowtail and
      shrimp has been developed. The drug was extracted with 0.2% metaphosphoric acid
      methanol (6 : 4), and the extracts were cleaned up on an Oasis HLB cartridge (200
      mg). The extracts were analyzed by LC-MS/MS using electrospray ionizationin the
      negative ion mode. The LC separation was performed on a Hypersil Gold C18 column
      (15 cmx2.1 mm i.d.) with a gradient system of 0.01% formic acid-acetonitrile as
      the mobile phase at a flow rate of 0.2 mL/min. The quantitative and confirmatory
      determination of NFZ was performed by selected reaction monitoring (SRM). The
      calibration graph for NFZ was rectilinear from 0.2 to 100 ng/mL with SRM. The
      recoveries of NFZ from samples fortified at 1 and 10 ng/g were 79.6-106.8%, and
      quantification limit was 0.2 ng/g for the drug. This is well below the detection
      limit (1 ng/g) set by the Japanese Food Sanitation Law.

PMID- 18633206
TI  - [Simple preprocessing method for multi-determination of 235 pesticide residues in
      cooked ingredients of foods by GC/MS and LC/MS/MS].
AB  - A simple preprocessing method was developed for multiresidue determination of
      pesticides in processed agricultural products. Residues were extracted from
      homogenized samples with acetonitrile in a glass centrifuge tube, followed by
      salting-out and partitioning with n-hexane. Co-extractives were removed by means
      of mini-column clean up. Analysis was performed by GC/MS and LC/MS/MS. The
      prepared sample solutions were examined for matrix effects. Matrix effects had
      both positive and negative effects on quantitative value. Calibration was
      achieved by preparing matrix-matched calibration standards to counteract the
      matrix effects. Of the 235 pesticides spiked at 0.05 or 0.10 microg/g (Method
      GC), 0.025 or 0.05 microg/g (Method LC) into 8 foods (garlic paste, diced green
      sweet pepper, green peas paste, celery paste, sweet potato paste, dried adzuki
      beans, boiled bamboo shoots, tomato paste), recoveries of 214 pesticides were
      between 50 and 100% and the coefficient of variation was below 20%. This method
      is useful as a multi-residue analysis method for screening of pesticides in
      foods.

PMID- 18633207
TI  - [Determination of hymexazol in agricultural products by GC-NPD].
AB  - A method for the determination of hymexazol in agricultural produdcts by gas
      chromatography with a highly sensitive nitrogen-phosphorus detector (GC-NPD) was
      investigated. Hymexazol was extracted with acetonitrile, and the acetonitrile
      layer was separated by salting-out. The water layer was loaded onto a Chem-Elut
      column. Hymexazol in the water layer was adsorbed on the column, and eluted with
      ethyl acetate. The acetonitrile layer and the eluate were mixed and evaporated.
      The residue was dissolved in ethyl acetate, and the sample solution was cleaned
      up on a C18 column. Hymexazol in the eluate was analyzed by GC-NPD with a high
      polarity capillary column (DB-FFAP) and highly deactivated inlet liner.
      Recoveries of hymexazol spiked in agricultural products (tomato, lemon, soybean
      and other samples) at the level of 0.1 mug/g ranged from 65.0 to 84.7%. The limit
      of detection was 0.02microg/g.

PMID- 18633208
TI  - [Multiresidue method for pesticides and veterinary drugs in bovine milk using
      GC/MS and LC/MS/MS].
AB  - A simple, sensitive and selective method with gas chromatography/mass
      spectrometry (GC/MS) and liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) has been developed to detect 342 pesticides and veterinary drugs
      contaminating bovine milk at the maximum residue limits (MRLs) defined in the
      "positive list system". Sample preparation was performed by extracting the
      analytes with acetonitrile, followed by salting-out with sodium chloride. For
      some pesticides, the extract was further cleaned up by n-hexane partitioning and
      PSA cartridge column chromatography. GC/MS-EI or -NCI was used to determine
      pesticide residues, while LC/MS/MS-ESI was applicable to the determination of
      pesticide and veterinary drug residues. The variation of the recoveries of these
      drugs at MRL was relatively wide; however the relative standard deviations of the
      recovery of each drug were within 28%, suggesting that the present method is good
      enough for use as a screening test for contaminants at the MRLs. These results
      show that this method is useful for multiresidue analysis of numerous pesticides
      and veterinary drugs in bovine milk.

PMID- 18633209
TI  - [Simultaneous determination of sedecamycin and terdecamycin in livestock products
      by LC/MS].
AB  - A simple and rapid LC/MS method for simultaneous determination of sedecamyin
      (SCM) and terdecamycin (TDM) in livestock products has been developed. SCM and
      TDM were extracted with acetonitrile. The extract was washed with n-hexane and
      then evaporated to dryness. The residue was dissolved in methanol, and injected
      into the LC/MS. The mass spectrometer was operated in the positive electrospray
      ionization (ESI) mode. LC separation was performed on a high-pH-resistant C18
      column with 10 mmol/L carbonic acid-ammonia buffer (pH 10.0)-acetonitrile as a
      mobile pahse. The recoveries from swine muscle and liver fortified at the levels
      of 0.01 and 0.05 microg/g were 77-88%, and those from poultry muscle and liver
      fortified at the levels of 0.01 and 0.3 microg/g were 51-93%. The quantitation
      limits of SCM and TDM were 0.008 microg/g and 0.005 microg/g, respectively.

PMID- 18633210
TI  - [Multiresidue determination of quinolones in animal and fishery products by
      HPLC].
AB  - A simple and rapid multiresidue method was developed for the determination of
      twelve quinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin,
      flumequine, marbofloxacin, nalidixic acid, norfloxacin, ofloxacin, orbifloxacin,
      oxolinic acid and sarafloxacin) in muscle, liver, chicken eggs, milk, prawn and
      rainbow trout. The quinolones were extracted from a sample with acetonitrile
      water (95 : 5). A fifth part of the filtered extract was diluted with water to
      keep the acetonitrile ratio at ca. 60%, and passed through a C18 mini-column. The
      eluate was evaporated to dryness, and the residues were dissolved in methanol
      water (30 : 70) for HPLC analysis. The quinolones were separated on a Inertsil
      ODS-3V column (4.6 mm i.d.x250 mm) with a gradient system of 0.1% phosphoric acid
      acetonitrile as the mobile phase, with fluorescence detection.No interfering peak
      was found on the chromatograms of animal and fishery products, except for milk.
      The recoveries of the quinolones were over 60% from the animal and fishery
      products fortified at 0.1 microg/g, and the quantification limits of the
      quinolones were 0.005 microg/g. This proposed method was found to be effective
      and suitable for the screening of the quinolones in animal and fishery products.

PMID- 18633211
TI  - [Survey of pesticide residues in imported cereal products (1994.4 approximately
      2006.3)].
AB  - A survey of pesticide residues in 490 imported cereal products on the Tokyo
      market from April 1994 to March 2006 was carried out. Eight kinds of
      organophosphorus pesticides (chlorpyrifos, chlorpyrifos-methyl, DDVP, diazinon,
      etrimfos, malathion, MEP and pirimiphos-methyl) were detected at levels between
      Tr (below 0.01 ppm) and 0.82 ppm from 91 samples. In our investigations,
      chlorpyrifos-methyl and malathion tended to be detected in samples from America,
      pirimiphos-methyl in those from Europe, and MEP in those from Oceania. Thus,
      pesticide residues seemed to be different in produce from different areas.
      Residue levels of these pesticides were calculated as between 0.08 and 13.2% of
      their ADI values according to the daily intake of cereal products. Therefore,
      these cereal products should be safe for normal usage.

PMID- 18633212
TI  - [Interstitial pneumonia--diagnosis and therapy].
AB  - Interstitial pneumonia is defined as a fibrotic lung disease in which the main
      lesion sites are in the alveolar interstitium, and develops into respiratory
      failure due to progression of fibrosis. Idiopathic interstitial pneumonia
      comprises seven types of different clinico-radiological-pathological disease
      entities. Among them, idiopathic pulmonary fibrosis (IPF) in which the histology
      is characterized as usual interstitial pneumonia (UIP) has a worse prognosis, and
      the histology is fundamentally different from other types of disease entities in
      terms of fibrotic nature. However, the histology of UIP shows a better prognosis
      when associated with collagen vascular diseases. Here, we attempt to review the
      whole spectrum of interstitial pneumonia, its classification, differential
      diagnosis, prognosis, and therapeutic problems.

PMID- 18633213
TI  - [Evidence and issues in standardization of intraperitoneal chemotherapy].
AB  - Intraperitoneal (i.p.) chemotherapy targets i.p. regional metastasis by
      maintenance of high-dose intensity. Thus, it is applied for cancers in which i.p.
      lesions limit the prognosis or QOL of patients. In ovarian cancer, ample evidence
      to support survival benefit of i.p. chemotherapy has been established, however,
      its standardization has not yet been accomplished. NCI has made efforts for the
      dissemination of and education in i.p. therapy, and GOG's research focuses on a
      less toxic i.p. regimen. In gastric cancer, the advantage of i.p. therapy has not
      been proved, and for its approval, phase I-III trial of i.p. with or without
      cytoreduction surgery should be initiated.

PMID- 18633214
TI  - [Intraperitoneal chemotherapy for ovarian cancer].
AB  - Standard therapy for advanced ovary cancer is T-C chemotherapy (paclitaxel,
      carboplatin) after initial cytoreductive surgery. Intraperitoneal (i.p.)
      chemotherapy has been studied for several decades to improve the survival rate in
      ovarian cancer. The results of the Gynecologic Oncology Group (GOG) 172 trial
      comparing i.p. vs intravenous administration(i.v.) of cisplatin and paclitaxel
      chemotherapy were published in 2006. It showed a survival benefit in favor of the
      i.p. arm. The NCI (National Cancer Institute) and GOG have conducted a meta
      analysis on the past seven phase III trials comparing i.p. vs i.v. that showed
      significant improvement in survival. NCI advised i.p. as the treatment of choice
      for patients with advanced ovarian cancer optimally operated. However, there are
      many problems that make it difficult to compare the complex regime of i.p. arms
      with the control arm, including the low completion rate of the i.p. and the fact
      that the control arm was not the present standard chemotherapy (T-C). Although it
      has a possibility to become the standard therapy for advanced ovarian cancer, the
      optimal i.p. regimen remains unclear. Clinical trials are needed to determine the
      optimal drug for i.p. and optimal number of i.p. administrator in order to
      improve the survival rate in patients with advanced ovarian cancer.

PMID- 18633215
TI  - [The current situation and subjects of the intraperitoneal chemotherapy for
      peritoneal dissemination in gastric cancer].
AB  - Many different chemotherapeutic modalities have been done for patients with
      peritoneal dissemination of gastric cancer. However, no regimen of chemotherapy
      has become the treatment of choice for the control of peritoneal dissemination.
      It is thought that intraperitoneal chemotherapy is effective to contact lesions
      directly and reduce its side effects. So, many kinds of anticancer agents,
      including cisplatin, via intraperitoneal administration have been tried for
      peritoneal dissemination therapy. However, they were not so effective. Recently,
      intraperitoneal taxane administration has proven very effective for the treatment
      and local control of severe peritoneal dissemination in gastric cancer. The
      response rate, including disappearance of as cites, was higher than that of MTX/5
      FU systemic chemotherapy. There is no evidence that intraperitoneal taxane is
      significantly more effective than systemic chemotherapy in gastric cancer. But we
      considered that intraperitoneal taxane was promising for peritoneal dissemination
      therapy and organized the Society for the Study of Peritoneal Dissemination in
      Gastric Cancer. To determine the safety profile and activity of docetaxel via
      intraperitoneal administration combined with S-1 for gastric cancer patients with
      peritoneal dissemination, a multi-centric phase I/II study is being carried out
      now. A phase III study should be conducted in future for further understanding
      and cooperation in a smoothly undertaken investigation.

PMID- 18633216
TI  - [Intrapleural chemotherapy--current status and problems in Japan].
AB  - The efficacy of anti neoplastic agents for chest catheter pleurodesis remains
      controversial, and little is known regarding the optimal treatment protocol. Of
      the various anti neoplastic agents, bleomycin and cisplatin are preferred for
      intrapleural therapy in Japan, and a wide variation among institutions is evident
      in agent doses and medication methods for pleurodesis. In many reported trials of
      anti neoplastic pleurodesis, problems exist such as disease heterogeneity, small
      sample size and differences in response criteria, and randomized control trials
      (RCTs) are needed to establish evidence. The JCOG 9515 trial randomly assigned
      patients to either the bleomycin (BLM) arm, the OK-432 arm, or the
      cisplatin+etoposide (PE) arm. Among them, OK-432 was demonstrated to be more
      effective than BLM or PE in terms of pleural progression-free survival.
      Intrapleural combination therapy (chemotherapy plus biological response
      modifiers) appeared to be superior to either alone, and further randomized
      studies are warranted.

PMID- 18633217
TI  - [Intrathecal infusion of the antineoplastic agents for meningeal dissemination].
AB  - One of the specific forms of progression of malignant tumors of the central
      nervous system is meningeal dissemination. Meningeal dissemination is a condition
      in which tumor cells migrate to the brain surface and sub arachnoid space via
      cerebrospinal fluid and then infiltrate there. This condition can arise from both
      primary and metastatic brain tumors, with reported incidences of 4.2% for primary
      tumors and 5.1% for metastatic tumors. Meningeal dissemination frequently arises
      from germinoma, medulloblastoma, ependymoma and glioblastoma in cases of primary
      brain tumors and frequently arises from breast cancer, lung cancer and gastric
      cancer in cases of metastatic brain tumors, known as meningeal carcinomatosis.
      The prognosis of meningeal dissemination is poor, and conventional treatments
      such as systemic chemotherapy and radiation therapy are ineffective. Intrathecal
      infusion of anti neoplastic agents is one of the options for treatment of
      meningeal dissemination. The advantage of intrathecal chemotherapy is that the
      anti neoplastic agent is rapidly diffused in the sub arachnoid space, and its
      duration of activity is long due to its slow clearance and metabolism. Routes of
      administration include infusion into the lateral ventricle by puncture of the
      Ommaya reservoir, infusion into the sub arachnoid space by lumbar puncture, or
      both of these procedures performed alternately or simultaneously, and methods of
      infusion include bolus injection and ventriculo lumbar perfusion. Commonly used
      drugs include methotrexate (MTX), cytarabine (Ara-C), and 3-[(4-amino-2-methyl-5
      pyrimidinyl)methyl]-1-(2-chloroethyl)- 1-nitrosourea hydrochloride (ACNU), and
      some new drugs have also begun to be used clinically. Although there are
      differences depending on the histological type of the tumor, the anti neoplastic
      agent administered and the method of administration, the response rate is about
      40-80% and mean survival time is about 4-25 months. Although side effects of the
      anti neoplastic agents are not as severe as with agents used for systemic
      chemotherapy, specific side effects include nonspecific drug-induced meningitis
      or ventriculitis, transient or permanent paralysis and leukoencephalopathy. These
      side effects can be alleviated by reducing the dose or discontinuing the anti
      neoplastic agents, and a small dose of an adrenocorticosteroid is sometimes
      administered simultaneously. Bacterial meningitis is another complication and
      requires discontinuation of anti neoplastic agents, removal of the Ommaya
      reservoir, or systemic or intrathecal administration of antibiotic agents.
      Although meningeal dissemination is a rare metastatic condition with a poor
      prognosis, there have been some reports of successful treatment using this
      method, which is expected to be widely used in the future.

PMID- 18633218
TI  - [Treatment of malignant pericardial effusion].
AB  - Cardiac tamponade is an emergency situation that warrants immediate evacuation of
      the pericardial fluid. Since the fluid tends to recur only by pericardiocentesis,
      various agents have been instilled into the pericardium to promote adhesion and
      obliteration of the cavity. Comparative studies of sclerosing agents for the
      management of malignant pericardial effusion include that comparing the Bleomycin
      group and non-administered group (JCOG) and another comparing bleomycin and
      doxycycline in 1996. Both studies recommended Bleomycin to control malignant
      pericardial effusion. Although instillation of drugs into the pericardium are
      reportedly safe, paracentesis or tube pericardiostomy are sometimes associated
      with an incidence of complications, some of which are fatal. These complications
      are assumed to occur in about 3% of the cases, even if an experienced physician
      proceeds using an echo guide. Though bleomycin is the recommended drug for the
      initial sclerosing agent in malignant pericardial effusion, physicians should
      consider the status and the prognosis of each case in the treatment of malignant
      pericardial effusion.

PMID- 18633219
TI  - [Phase II study of combination of gemcitabine and carboplatin in advanced non
      small cell lung cancer (an interim report)].
AB  - A phase II study of combination therapy with gemcitabine and carboplatin was
      performed in 24 patients with advanced non-small cell lung cancer to evaluate the
      efficacy and safety of the therapy. Patients were treated at 3-week intervals
      with two courses or more of the regimen consisting of gemcitabine 1,000 mg/m(2)
      and carboplatin AUC 2 on day 1 and day 8. Response rate was 37.5% (9/24) (95%
      confidence interval: 18.8-59.4%). The median number of courses was 3(range 1-8).
      The time to progressive disease was 147 days and the median survival was 338
      days. The one-year survival rate was 45.8%. The major toxicity was
      hematotoxicity, and >or=grade 3 neutropenia(58.3%)and thrombocytopenia (45.8%)
      occurred. None of >or=grade 3 non-hematotoxicities were evident, but grade 2 rash
      (8.3%) and fever (8.3%), nausea (4.2%), vomiting (4.2%) occurred. None of the
      other severe toxicities appeared. In conclusion, this combination therapy was
      suggested to be tolerable with a high response rate and safety, and we plan to
      continue testing.

PMID- 18633220
TI  - [Feasibility and anti-tumor activity of postoperative adjuvant chemotherapy with
      gemcitabine for resected pancreatic cancer].
AB  - The feasibility and anti-tumor activity of gemcitabine (GEM) as postoperative
      adjuvant chemotherapy were evaluated retrospectively. Between September 1998 and
      June 2007, patients with resected invasive pancreatic cancer (stage III, IVa,
      IVb) were given adjuvant chemotherapy with GEM (GEM group, n=10) or did not
      receive chemotherapy (n=11). Started the administration of GEM 38.5 days after
      surgery, and the mean duration was 15.4 months. Grade 3 or 4 adverse event was
      not observed in the GEM group. There was a significant difference in overall
      survival between the GEM group and the no-chemotherapy group (p=0.037), but there
      was no significant difference in disease-free survival between the two groups.
      Adjuvant chemotherapy with GEM was feasible and showed a benefit in patients with
      invasive pancreatic cancer.

PMID- 18633221
TI  - [Predictive factors of nausea/vomiting of breast cancer patients receiving FEC
      and AC chemotherapy].
AB  - INTRODUCTION: It is largely believed that nausea/vomiting during cancer
      chemotherapy is caused by both the medical and personal factors of the patient.
      This study was aimed at examining whether the monitoring of risk factors prior to
      the therapy would help predict nausea/vomiting. METHOD: In the fifteen months
      between April 2006 and June 2007, breast cancer patients, receiving FEC and AC
      chemotherapy at the Outpatient Chemotherapy Room, were interviewed. Before they
      received their first treatment, each patient was asked to reply as to five risk
      factors: age, history of motion sickness, habitual drinking, history of morning
      sickness, and anxiety. Three weeks later, when they came back for their second
      treatment, CTCAE was conducted to assess their symptoms of nausea and vomiting.
      Fisher's exact probability test was used for the statistical analysis. RESULTS:
      49 patients were studied. The relative risk ratios of vomiting were as follows:
      Age 1.57; motion sickness 2.15; habitual drinking 0.97; morning sickness 1.54;
      and anxiety 3.15. Only anxiety showed a significant difference(p=0.019). The
      associated risk ratios of nausea were: age 2.00; motion sickness 1.57; habitual
      drinking 1.04; morning sickness 1.37; and high levels of anxiety 2.28. Only
      anxiety showed a significant difference(p=0.018). The number of risk factors did
      not show a significant difference. CONCLUSION: The study shows that anxiety may
      be one of the risk factors that would cause severe nausea or vomiting during
      cancer chemotherapy.

PMID- 18633223
TI  - [Prevention of irinotecan hydrochloride-induced diarrhea by oral administration
      of Lactobacillus casei strain Shirota in rats].
AB  - Irinotecan hydrochloride is an inhibitor of DNA topoisomerase I enzyme by its
      main active metabolite SN-38. However, irinotecan-induced severe diarrhea has
      often limited its more widespread use. We assessed the effect of oral
      administration of Lactobacillus casei strain Shirota (LcS) on irinotecan-induced
      diarrhea in rats. Rats in the LcS group were administered LcS (1.64 x 10(11)
      cfu/0.5 g/3 mL saline) orally for 28 days. Fourteen days later, irinotecan was
      given for 4 days (100 mg/kg i. p.). Control group rats were administered 3 mL
      saline orally for 28 days together with irinotecan, as in the LcS group. As a
      result, LcS significantly inhibited the weight decrease due to irinotecan and the
      food intake was greater than in the controls. The delayed diarrhea symptoms
      induced by irinotecan also seemed to be improved. Although we cannot conclude why
      LcS improved the side effect of irinotecan, LcS might inhibit beta-glucuronidase
      activity, which is produced by intestinal flora and plays a key role in the
      development of irinotecan-induced delayed diarrhea. Further investigations
      including this issue are warranted.

PMID- 18633222
TI  - [Study of a relationship between a change in the urinary uracil value after a S-1
      long-term administration and the recurrence of stomach cancer].
AB  - S-1 has been reported good results in the treatment of stomach cancer. However, a
      DPD activity change has also been reported as one of the causes for a recurrence
      though some recurrence cases observing a state of tumor being unchanged
      continuously for more than 1 year. Therefore the urinary uracil value, which
      could simply be predicted in the DPD activity at the time of a recurrence after
      having administered S-1 for a long-term, was measured. And the urinary uracil
      value was examined whether it could become an index of recurrence compared with a
      healthy 5-person example as reference. In the result, a monthly difference in
      change of the urinary uracil values of the reference was small. However, the
      urinary uracil values in patients who were administered S-1 more than 6 months
      but recurred, were significantly lower comparing with the healthy 5-person
      example. We concluded from this study that the change in DPD activity due to an
      induction of DPD by 5-FU and metastasis of cancer caused the recurrence and lower
      a urinary value. The urinary uracil value reflecting DPD activity of the whole
      body could be used as an index of recurrence at the time of long-term dosage of S
      1. Furthermore, a measurement of the urinary uracil value seems to be promising
      for estimation and evaluation of the cure.

PMID- 18633224
TI  - [Involvement of zinc in taste disturbance occurring during treatment for
      malignant tumor in the chest and the effects of polaprezinc oral disintegrating
      tablets (a retrospective study)].
AB  - We analyzed the correlation between serum zinc levels and taste disturbance, and
      between patient backgrounds and serum zinc levels or taste disturbance, and
      evaluated the effects of polaprezinc oral disintegrating tablets on taste
      disturbance in 29 patients with lung cancer and one patient with malignant
      pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed
      in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with
      taste disturbance (p=0.0227). Serum zinc levels were significantly lower
      (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males.
      Polaprezinc improved taste disturbance in 5 of 8 patients.

PMID- 18633225
TI  - [CR obtained by CPT-11 and CDDP combination-therapy in a small-cell lung-cancer
      patient through effective pharmaceutical care].
AB  - We encountered a 64-year-old UGT1A1*28 heterotype patient who received CPT-11 and
      CDDP chemotherapy for Stage III A small-cell lung-cancer and developed grade 4
      neutropenia as assessed by CTCAE v3.0 in Pharmaceutical Management. The
      therapeutic effect was good; 4 courses of chemotherapy could be safely
      administered at 1/3 of the applied dose of CPT-11, and CR was obtained. In this
      period, we participated in selecting antibiotics to neutropenia and CPT-11
      closing regimen as pharmacists. Additionally, we carefully monitored patients
      about their bowel pattern and hematotoxicity, and collected information about
      gene searching for the patient and the Hospital Ethics Committee. The analysis of
      the gene polymorphism of CPT-11 is useful to predict the occurrence of serious
      side effects, but this judgment cannot easily be made clinically. In the event of
      a marked decrease in the neutrophil count of a patient during the first courses
      of treatment with CPT-11, we believe that it is important to consider gene
      polymorphism, to closely monitor the symptoms and laboratory parameters, and to
      give a smaller dose of the drug.

PMID- 18633226
TI  - [A long-surviving patient with lung pleomorphic carcinoma treated with
      postoperative carboplatin and paclitaxel combination chemotherapy].
AB  - We presented the case of a 46-year-old man with no medical or family history but
      with a history of smoking 3 packs of cigarettes per day for the past 25 years. He
      was admitted to our hospital due to hemoptysis. Chest computed tomography
      revealed a tumor of right upper lung and interstitial pneumonia in the
      surrounding lung parenchyma. He was operated upon and diagnosed with stage IIB
      pleomorphic carcinoma of the lung with invasion of the chest wall. He underwent
      three courses of postoperative carboplatin (CBDCA) (area under the curve 5 on day
      1, every 3 weeks and paclitaxel(PTX) (200 mg/m(2); day 1, every 3 weeks)
      combination chemotherapy. No recurrence was observed for a period of 760 days
      after the operation. According to previous reports, lung pleomorphic carcinoma is
      aggressive and has a poor prognosis. Further, the significance of chemotherapy in
      the management of this disease has not been established. Postoperative
      combination chemotherapy of CBDCA and PTX may result in a good prognosis for this
      disease.

PMID- 18633227
TI  - [A case of interstitial pneumonia induced by S-1/irinotecan combination therapy].
AB  - A 67-year-old man with multiple liver metastases of colonic cancer was treated
      with combination therapy of S-1 and irinotecan (CPT-11): S-1 (120 mg/day)
      administered orally for 14 consecutive days followed by 14 days rest. CPT-11 (100
      mg/m(2)) was given as a 2-hour infusion on day 1 and 15. The patient complained
      of high fever and subsequent exertional dyspnea in the middle of the second
      course of S-1/CPT-11 therapy. He was hospitalized with severe hypoxemia. CT scan
      showed extensive ground glass and consolidative changes in bilateral lungs.
      Steroid pulse therapy with oxygen therapy remarkably improved his symptoms, and
      abnormal findings on CT scan also resolved. Drug-induced pneumonia needs to be
      considered in the differential diagnosis when patients treated with S-1/CPT-11
      combination therapy present high fever and dyspnea.

PMID- 18633228
TI  - [A case of locally advanced breast cancer successfully treated by pre-operative
      systemic therapy using paclitaxel and trastuzumab].
AB  - A 53-year-old woman with locally advanced breast cancer exhibiting skin edema and
      axial lymph-node swelling was treated by pre-operative systemic therapy. A core
      needle biopsy revealed the tumor to be a solid-tubular carcinoma which was
      hormone receptor-negative and HER2-positive. Six courses of an anthracycline
      based regimen (5-fluorouracil, epirubicin, cyclophosphamide; FEC) and 6 weekly
      courses of paclitaxel concomitant with trastuzumab were sequentially
      administered. After those treatments, the tumor presented as clinically CR. An
      incisional biopsy of the left breast showed that the tumor was completely
      eliminated, with ductal carcinoma absent upon pathological examination.

PMID- 18633229
TI  - A case of advanced breast cancer associated with development of liver atrophy
      with progressive liver failure during treatment.
AB  - A 44-year-old-female came to our hospital with abdominal distension in April
      2005. She had been diagnosed with breast cancer in 1991, which was treated with
      mastectomy, postoperative radiation therapy,and a five-year course of hormonal
      therapy. An abdominal computed tomography (CT) scan revealed multiple
      hypoattenuated lesions in both lobes of her liver, which were diagnosed as
      metastatic breast cancer by liver biopsy. Weekly chemotherapy with paclitaxel was
      initiated on May 13. Trastuzumab and tamoxifen were added after two weeks. After
      six months of treatment, the CT scans showed reductions in the size of her
      multiple liver metastases along with the development of slight irregularities in
      the liver surface. Liver dysfunction was improved,and tumor marker BCA225 levels
      significantly decreased. After ten months of treatment, the CT scan showed
      nodular irregularity of the hepatic borders with deformation and atrophic
      changes. After twelve months of treatment,she was readmitted with abdominal
      distension and lower extremity edema. Increased ascites and appearance of
      esophageal varices were observed. Laboratory values were compatible with
      decompensation of liver function,although BCA225 levels still remained low.
      Despite discontinuation of chemotherapy and hormonal therapy at this time, she
      died from liver failure less than two weeks later. The atrophic changes and liver
      failure are suspected to have resulted from the chemotherapy and/or hormonal
      therapy.

PMID- 18633230
TI  - [A case of primary breast cancer who responded remarkably to the neoadjuvant
      chemotherapy with the combination of docetaxel and cyclophosphamide].
AB  - A 67-year-old woman visited our hospital with suspicion of right breast cancer.
      She underwent core needle biopsy, and her disease was diagnosed as breast cancer
      (invasive ductal carcinoma, ER- and PgR- positive, HER2-negative). We chose
      neoadjuvant chemotherapy, because the tumor size was over 3 cm in diameter and
      she wished to conserve her breast. She was elderly, and so without anthracycline
      base, we used a combination of docetaxel (75 mg/m(2)) and cyclophosphamide (600
      mg/m(2)) q3w 6 cycles followed by breast-conserving therapy. During treatment,
      the patient remained very well and showed no major side effects except grade 4
      neutropenia on an outpatient basis. After 6 cycles, ultrasonography and
      mammography indicated the residual tumor, but breast MRI did not detect any
      tumor. Pathological examination showed absence of invasive tumor or only focal
      residual tumor cells (QpCR). We concluded that the combination of docetaxel and
      cyclophosphamide was a good option for neoadjuvant chemotherapy for early breast
      cancer.

PMID- 18633231
TI  - [Breast cancer during pregnancy--a case report].
AB  - Pregnancy-associated breast carcinoma is generally defined as cancer that occurs
      during pregnancy or within 1 year of delivery, although treatment options are the
      most complicated when the disease is diagnosed during pregnancy. We report the
      case of a 30-year-old woman who was diagnosed with breast cancer at her 9th week
      of pregnancy. The patient initially had mastectomy with axillary lymph node
      dissection. She began adjuvant therapy with 3 courses of
      epirubicin/cyclophosphamide at 19 weeks of gestation. After delivery of a healthy
      child, she received one course of epirubicin/cyclophosphamide and 4 courses of
      docetaxel. Although the data are limited, pregnant patients with cancer can be
      treated with systemic chemotherapy with minimal risks to the fetus during the
      second or third trimester. Management of breast cancer during pregnancy requires
      an interdisciplinary care team and careful consideration of the patient's stage
      of disease, the gestational age of the fetus, and the preferences of the patient
      and her family.

PMID- 18633232
TI  - [Case of gastric cancer with recurrence of carcinomatous lymphangiosis of the
      lung 7.6 years after surgery and successfully treated with S-1/low-dose
      CDDP/Lentinan combination therapy].
AB  - A 78-year-old woman underwent gastrectomy for type 3 gastric cancer with pyloric
      stenosis, which was detected in November 1997. Thoracic and abdominal CT and
      other diagnostic procedures were conducted regularly for 5 years after surgery.
      The patient was recurrence-free and her clinical course was satisfactory.
      Starting in early May 2005, however, she began to experience respiratory
      difficulty at exertion, which exacerbated rapidly thereafter. Examination at a
      department of respiratory physiology led to a diagnosis of a recurrence of
      stomach cancer and carcinomatous lymphangiosis+lymphatic metastasis to the
      peritoneal cavity. She was referred to us for palliative care. The accentuated
      respiratory difficulty was eased with oxygen inhalation and opioid
      administration. With improvement in her respiratory condition, a combination of S
      1 80 mg/day, CDDP 10 mg x once/week and Lentinan 1 mg x twice/week, was
      initiated. Within about 2 weeks, her respiratory difficulty was eliminated and
      after 4 weeks x 2 courses, the tumor images were no longer recognized in the
      thoracic and abdominal CTs. The combination therapy of S-1/low-dose CDDP/Lentinan
      is free of evident adverse effects and may be a potent therapeutic alternative as
      a palliative therapy for malignant stomach cancers in elderly patients or those
      in a poor systemic condition.

PMID- 18633233
TI  - [A case of gastric cancer with peritoneal dissemination responding to combination
      chemotherapy with oral fluoropyrimidine and weekly paclitaxel].
AB  - We report a case in which combination chemotherapy with oral fluoropyrimidine and
      weekly paclitaxel was effective for gastric cancer with peritoneal dissemination.
      A 44-year-old woman suffering from advanced gastric cancer with peritoneal
      dissemination underwent total gastrectomy. After surgery, combination
      chemotherapy with doxifluridine plus weekly paclitaxel was administered on an
      outpatient basis, and was effective without any sign of relapse of the disease
      for a year. However, she complained of dull abdominal pain, and ascites was
      observed 13 months after surgery. She received combination chemotherapy with S-1
      plus weekly paclitaxel. The ascites decreased after 3 courses of the
      chemotherapy. No major adverse effect was observed except for grade 1 anemia and
      grade 2 hair loss. She has been well with the chemotherapy on an outpatient basis
      18 months after surgery.

PMID- 18633234
TI  - A three-year survivor case of gastric cancer with peritoneal dissemination--an
      outpatient with second-line weekly paclitaxel.
AB  - This case report describes a three-year survivor case by weekly paclitaxel, who
      had peritoneal dissemination of gastric cancer resistant to methotrexate and 5
      fluorouracil therapy. A 62-year-old female with massive ascites, abdominal pain,
      and difficulty in eating received a weekly paclitaxel schedule which consisted of
      a 1-hour infusion of paclitaxel (70 mg/m(2)) given once a week for three weeks
      followed by a 1-week rest, repeated every four weeks. Short course premedication
      was given 30 minutes prior to paclitaxel. The administrations could be performed
      on an outpatient basis with transient grade 3 neutropenia requiring no specific
      medication. Neither hypersensitivity reactions nor peripheral neuropathy
      developed. A dramatic disappearance of ascites and relief of abdominal pain, as
      well as a rapid recovery of food intake enabled the patient to be withdrawn from
      nutritional support through central venous catheter, indicating this schedule's
      contribution to improve her quality of life. A three-year survival from the
      commencement of weekly paclitaxel without evidence of relapse was confirmed.
      Weekly paclitaxel was based on the dose-dense concept, where cumulative
      paclitaxel exposures by frequent, repetitive administration have a more potent
      antitumor effect than higher dose 21-day schedule. Encouraging aspects in the
      weekly paclitaxel schedule in this report are that the survival time is
      considered to be satisfactorily long as compared with those of other case reports
      in the literature achieved by a convenient outpatient use with acceptable
      toxicities, leading to a comprehensive contribution to improve patient quality of
      life.

PMID- 18633235
TI  - [A case of effective treatment with chemosensitivity test-guided chemotherapy for
      advanced pancreatic and gastric cancer with peritoneal metastasis].
AB  - A 63-year-old man with abdominal pain was diagnosed as locally advanced
      pancreatic tail cancer and gastric cancer with peritoneal metastasis based on
      computed tomography (CT) and gastrointestinal series. Preoperative serum CA19- 9
      was 1,357 U/mL. During laparotomy, peritoneal dissemination was observed and
      confirmed pathologically. An ileoileostomy was performed and peritoneal tissue
      was submitted to a chemosensitivity test. Based on the chemosensitivity test, CPT
      11 (50 mg/body), 5-FU (750 mg/body), and Leucovorin (375 mg/body) were
      administered intravenously once a week for 3 weeks with a 1-week rest as 1
      course. The patient received 9 courses of chemotherapy until progressive disease.
      Stable disease in tumor size was observed and serum CA19-9 level dropped to 81
      U/mL. He remained well without any symptoms and pursued normal activity for 15
      months. He died of peritoneal dissemination 26 months after diagnosis.
      Chemosensitivity test-guided chemotherapy seems to be an effective regimen as
      individualized chemotherapy for advanced pancreatic and gastric cancer.

PMID- 18633236
TI  - [A case of advanced pancreatic cancer responding to combination chemotherapy with
      the individual maximum repeatable dose of gemcitabine and oral S-1].
AB  - The patient was a 70-year-old man with metastatic pancreatic cancer. After he
      received combination chemotherapy with gemcitabine and oral S-1 on day 1, he
      experienced severe general fatigue, anorexia and nausea. Then we changed the dose
      of gemcitabine from 1,000 mg/m(2) 2 to 500 mg/m(2) according to the criteria for
      an individual maximum repeatable dose (iMRD) determination method on day 8. His
      general condition recovered, and treatment schedule of gemcitabine with S-1 was
      continued sequentially at an outpatient clinic. His tumor marker levels, and the
      sizes of primary pancreatic tumor and liver metastatic lesions remarkably
      decreased. Partial response has been obtained for 7 months.

PMID- 18633238
TI  - [A long-term survivor after relapsed acute myeloblastic leukemia with
      anthracycline dilated cardiomyopathy].
AB  - We watched and analyzed patient cardiac functions especially with a "Phased
      tracking method" to detect rapid motion of the heart. The patient suffered from
      congestive heart failure while depending on anthracycline cumulative doses, but
      now has been living more than 10 years after relapsed acute myeloblastic
      leukemia. To avoid congestive heart failure with increasing highly tumoricidal
      anthracycline doses, cardiac function should be monitored closely in connection
      with treatment schedules and proposed accurate therapeutic index.

PMID- 18633237
TI  - [A case of sigmoid colon cancer with metastases of para-aortic lymph nodes
      treated with curative resection after irinotecan plus 5-fluorouracil and l
      leucovorin combination chemotherapy].
AB  - A 54-year-old woman visited our hospital with a chief complaint of lower
      abdominal pain and melena. The patient was diagnosed with sigmoid colon cancer
      using colonoscopy. Abdominal CT revealed metastases to para-aortic lymph node, so
      our diagnosis was unresectable sigmoid colon cancer. She underwent a transverse
      colostomy to avoid stenosis. Two weeks after surgery, she underwent a 1-week
      chemotherapy regimen (CPT-11 80 mg/m(2)/week+5-FU 2,000 mg/m(2)/week+l-LV 250
      mg/m(2)/week) modified AIO regimen combined irinotecan for 3 weeks, followed by a
      1-week rest interval as one course. Throughout the period of treatment, there was
      no adverse event, and this regimen has been maintained for 5 courses. After 5
      courses of chemotherapy, primary tumor and metastases to para-aortic lymph nodes
      were remarkably reduced on colonoscopy and abdominal CT. So, she could undergo
      curative resection. Pathological efficacy was Grade 3, a complete response. This
      combination therapy may well be useful for advanced colon cancer patients.

PMID- 18633239
TI  - [A case of hepatic encephalopathy induced by adverse effect of morphine sulfate].
AB  - A 63-year-old man with liver cirrhosis and hepatocellular carcinoma presented
      with abrupt encephalopathy with markedly elevated blood ammonia levels. He was
      found lying down in front of the hospital 2 days after treatment of right
      hypochondrial pain with sustained-release oral morphine sulfate. He tended to be
      constipated before receiving morphine sulfate. The excess production of ammonia
      due to his constitutional constipation exacerbated by the use of oral morphine
      was thought to be the causal association with transient hepatic encephalopathy.
      He regained consciousness by receiving aminoleban intravenously and
      anticonstipating suppository. We realized that much care should be taken to avoid
      such opioid-related constipation at the time of pain management for quality of
      life improvement in patients with cancer pain.

PMID- 18633240
TI  - [Clinical implications of bortezomib in frontline treatment of newly-diagnosed
      multiple myeloma].
AB  - Although multiple myeloma (MM) remains incurable with conventional treatments
      including high-dose melphalan plus autologous stem cell transplantation,
      therapeutic strategy has been revised because of the recent introduction of a
      novel agent such as bortezomib (Bz). The proteasome inhibitor bortezomib is
      approved for the treatment of advanced MM with at least one prior therapy in
      Japan at this moment; however, there is a growing body of clinical evidence
      showing its effectiveness alone and in combination in the frontline setting, with
      high response rates and consistently high rates of complete response. This review
      therefore focuses on the clinical data based on the previous studies of Bz in the
      treatment of newly-diagnosed MM.

PMID- 18633241
TI  - [Pemetrexed].
AB  - Pemetrexed (ALIMTA, LY231514) is a novel, multi targeted antifolate chemotherapy
      agent that is active in various tumors including mesothelioma, NSCLC, breast,
      colon and bladder carcinoma. Pemetrexed inhibits several enzymes in the folate
      pathway including thymidylate synthase, dihydrofolate reductase, and glycinamide
      ribonucleotide formyltransferase. Pemetrexed is approved in the United States and
      a number of European Union countries for use in the treatment of mesothelioma,
      and the second-line treatment of advanced NSCLC. However, in Japan, pemetrexed
      was approved for use only in combination with cisplatin in the treatment of
      mesothelioma in January 2007. This approval was granted on the basis of a phase
      III trial of pemetrexed in combination with cisplatin versus cisplatin alone in
      patients with malignant pleural mesothelioma. Treatment with pemetrexed plus
      cisplatin and vitamin supplementation, resulted in superior survival time, time
      to progression, and response rates compared with treatment with cisplatin alone.
      In addition, in a phase III trial of pemetrexed versus docetaxel in patients with
      NSCLC previously treated with chemotherapy, treatment with pemetrexed resulted in
      clinically equivalent efficacy outcomes, but with significantly fewer side
      effects including grade 3 or 4 neutropenia , neutropenic fever, and alopecia,
      compared with docetaxel. Therefore, pemetrexed should be considered a standard
      treatment option for second-line NSCLC in US and most of EU. Addition of folic
      acid and vitamin B12 significantly reduced the toxicity of pemetrexed, especially
      hematologic toxicity and gastrointestinal toxicity. Pemetrexed is the expected
      agent for use in high risk patients, especially elderly or poor performance
      status patients.

PMID- 18633242
TI  - [Cancer chemoprevention-basic and clinical aspects].
AB  - Cancer chemoprevention is the use of agents to inhibit, delay or reverse
      carcinogenesis, and was proposed in the United States in view of the cost
      benefits. Since recent progress in molecular biology revealed several signal
      transduction routes in carcinogenesis, the search for mechanism-based
      chemopreventive agents is under way. Many chemopreventive clinical trials for
      various cancers including colorectal cancer, prostate cancer and breast cancer,
      have been performed. Chemoprevention to eradicate viruses or bacteria such as
      hepatitis viruses or Helicobacter pylori is also important in order to prevent
      development of cancer.

PMID- 18633243
TI  - [Ethnic differences of genetic polymorphisms in cancer chemotherapy].
AB  - The frequency of polymorphisms of CDA was analyzed and the correlation between
      polymorphisms of CDA and toxicity was evaluated. CDA*3 genotype strongly
      influenced the metabolism of the drugs and patients with CDA*3 homotype
      experienced severe toxicity, and the frequency differed among persons of
      different ethnic origin. Ethnic differences in PK and PD were demonstrated by
      common arm trials in USA and Japan. Pharmacogenomic differences which determine
      them should be more intensively been studied.

PMID- 18633244
TI  - [EGFR and gefitinib (Iressa)].
AB  - We summarized the relationship between EGFR gene polymorphisms/mutations and
      gefitinib(Iressa). The SNPs of CA-simple sequence repeat of EGFR intron 1 and
      promoter sequence were reported to be related to the sensitivity and/ or toxicity
      of gefitinib(Iressa). Many reports have shown that there are differences between
      gefitinib responders and non-responders in the frequency of activating mutations
      and/or amplification in the EGFR gene, which suggests that such mutations might
      be predictive markers for sensitivity to gefitinib. However, there are known to
      be gefitinib-sensitive and intermediate-sensitive tumors that have no activating
      mutations in the EGFR gene, including gene amplification. SNPs in EGFR gene may
      be one of candidates for predictors of sensitivity. On the other hand, the
      incidence of gefitinib-induced lung injury was 3.98% in Japan(case-control study,
      AstraZeneca), which is higher than the correspondence rate, 0.3%, in the USA(FDA
      Approval Letter). Further studies about the prediction of drug-induced
      interstitial lung disease including SNPs analyses of the EGFR gene and other
      related molecules.

PMID- 18633245
TI  - [Role of UGT1A1*28 and UGT1A1*6 for irinotecan-induced adverse drug reaction].
AB  - Irinotecan is widely used in the treatment of colorectal, gastric, and lung
      cancers. However, adverse drug reactions such as severe diarrhea and neutropenia
      limit the dose of this drug. Irinotecan is metabolized by carboxylesterase to
      form an active metabolite, 7-ethyl-10-hydroxycamptothecin(SN-38), which in turn
      is subsequently conjugated by UGT-glucuronosyltransferase 1A1(UGT1A1)to yield an
      inactive form, SN-38 glucuronide(SN-38 G). The UGT1A1 gene polymorphisms
      contribute to the individual variation in adverse events among patients
      administered irinotecan. However, the distribution of polymorphisms shows large
      interethnic differences. The distribution of UGT1A1*28 greatly differs between
      Caucasians and Japanese; the frequency of UGT1A1*28 is high in Caucasians,
      whereas it is low in Asians including Japanese. Recently, it has been
      demonstrated that genetic variants of UGT1A1*6 in addition to UGT1A1*28 are
      associated with the occurrence of adverse events in irinotecan chemotherapy in
      Asians. This review summarizes recent studies to outline the role of UGT1A1*28
      and UGT1A1*6 for irinotecan-induced adverse drug reaction in Japanese cancer
      patients.

PMID- 18633246
TI  - [Vinca alkaloid and MDR1].
AB  - Vinca alkaloids inhibit microtubule formation by binding to tubulin. There are
      four clinically available vinca alkaloids including vincristine, vinblastine,
      vindesine, and vinorelbine. P-glycoprotein(P-gp)is the one of the efflux
      adenosine triphosphate(ATP)-binding cassette family transporters and is the
      encoded product of MDR1 gene. P-gp is overexpressed not only in tumor cells
      resistant to multiple anticancer agents but also found in normal cells such as
      liver, gastrointestinal tract and kidney, working as a biological defense
      mechanism. Single nucleotide polymorphisms for MDR1 in exon 12(1236), exon
      21(2677), and exon 26(3435)have been well studied. Although C1236T and C3435T do
      not change the amino acid, G2677T and G2677A result in amino acid substitution of
      Ala893Ser and Ala893Thr, respectively. In the use of haplotypes to predict
      vincristine pharmacokinetics, the correlation between the haplotypes and the
      elimination half-life was reported. Many studies of the relationship between
      polymorphism/haplotype for MDR1 and pharmacodynamics including efficacy and
      toxicity of chemotherapy have been explored.

PMID- 18633247
TI  - [Cyclophosphamide and CYP2B6].
AB  - Members of the hepatic cytochrome p450 superfamily(CYP)play an important role in
      the metabolism of many therapeutic drugs. There is a marked individual
      variability in the CYP-mediated drug metabolism. One of the main factors of the
      CYP activities is a polymorphism of the CYP genes. Polymorphisms of the CYP genes
      contribute to the variation in the drug-metabolic rate. The polymorphic nature of
      the CYP genes affects the individual drug response and adverse reactions.
      Cyclophosphamide(CPA)exerts its effect after biotransformation to 4-hydroxy-CPA
      by hepatic CYP. Several CYPs have been reported to mediate this reaction.
      Especially CYP2B6 is thought to be the key enzyme in the CPA metabolism. CYP2B6
      is highly polymorphic, and it has been reported that the genetic backgrounds of
      CYP2B6 in Japanese and Caucasians are different. CYP2B6*6, which is a relatively
      common allele in the Japanese population, affects the gene expression and
      activities of CYP2B6 in vitro. The homozygote of CYP2B6*6 patients with malignant
      lymphoma and breast cancer treated with CPA showed higher clearance and shorter
      half-life of plasma CPA. In addition, homozygous CYP2B6*5 patients with
      proliferative lupus nephritis had a significantly higher probability of reaching
      end-stage renal disease by pulse CPA treatment. Other gene polymorphisms of
      CYP2B6 also affect the CPA metabolism in vitro. However, the current knowledge of
      CYP2B6 polymorphism is not sufficient to predict its efficacy and safety for the
      individual patient in CPA therapy. Further studies are needed for clinical use.

PMID- 18633248
TI  - [Impact of single nucleotide polymorphisms in glutathione S transferase gene
      GSTP1 in the treatment with oxaliplatin based chemotherapy].
AB  - Oxaliplatin has been the main treatment of choice in colorectal cancer in
      advanced settings. However, cellular mechanisms for the uptake, intracellular
      distribution and efflux of oxaliplatin are unknown. GST(glutathione S
      transferase)is member of a superfamily of metabolic enzymes that play an
      important role in the cell defense system. Current data suggest that GST-pi is
      associated with increased resistance to platinum-based chemotherapy. Specific
      roles for the single nucleotide polymorphisms in GST-pi gene GSTP1 in the
      treatment with oxaliplatin based chemotherapy, have been demonstrated in recent
      years.

PMID- 18633249
TI  - [Trastuzumab and Fcgamma].
AB  - Trastuzumab is a recombinant humanized monoclonal antibody directed against the
      human epidermal growth factor receptor 2(HER2). ADCC is considered to be a major
      mechanism of anti-tumor effect of trastuzumab. The difference in subtype and gene
      polymorphism of Fcgamma receptor of effecter cells causes difference in affinity
      to Fc fragment of antibody and in ADCC activity. Consequently, it may cause the
      difference of trastuzumab treatment efficacy. These findings suggest the
      importance of gene polymorphism in strategy of new therapeutic antibody
      development and predict of treatment efficacy.

PMID- 18633250
TI  - [Genetic polymorphisms related to fluoropyrimidine sensitivity and toxicity].
AB  - Fluoropyrimidine such as 5-fluorouracil(5-FU)exerts its antitumor activities via
      anabolism by several enzymes. Genetic polymorphisms of these enzymes related to
      sensitivity and toxicity of fluoropyrimidines are reviewed. Expression of
      thymidylate synthase(TS), a target enzyme of 5-FU, is regulated by variable
      number of a 28 bp tandem repeat in the enhancer region. The double tandem repeat
      is associated with low TS expression, and consequently, patients with double
      tandem repeat demonstrated higher sensitivity to 5-FU than those with triple
      tandem repeat. Single nucleotide polymorphism within the second tandem repeat and
      loss of heterozygosity are also reported to be related to fluoropyrimidine
      sensitivity. In addition, patients having a 6 bp deletion in 3'-UTR region showed
      remarkably high antitumor activity by 5-FU based chemotherapy. Genetic variations
      in 5-FU catabolic enzymes can also have a profound effect on 5-FU toxicity. So
      far 39 mutations/ polymorphisms have been identified in dihydropyrimidine
      dehydrogenase(DPD)gene, a major catabolic enzyme of 5- FU. Among them, IVS14+1G>A
      is reported to be highly associated with severe toxicity caused by chemotherapy
      with fluoropyrimidine. A polymorphism that may influence the efficacy of 5-FU by
      influencing folate pools is that of the methylenetetrahydrofolate
      reductase(MTHFR)gene. C677T mutation was associated with a higher response rate
      on 5-FU/folinic acid chemotherapy. Prospective clinical trials to confirm the
      predictability of genetic polymorphism for sensitivity and toxicity of 5-FU
      should be performed.

PMID- 18633251
TI  - [Randomized phase II study of carboplatin/paclitaxel followed by gemcitabine
      versus carboplatin/gemcitabine followed by docetaxel in patients with advanced
      nonsmall cell lung cancer].
AB  - PURPOSE: To evaluate the chemotherapeutic regimens suitable for the outpatient
      settings, we conducted a randomized phase II study of carboplatin/paclitaxel
      followed by gemcitabine versus carboplatin/gemcitabine followed by docetaxel.
      METHODS: Group CP(n=25): carboplatin AUC 6.0 day 1 and paclitaxel 70 mg/m2 day 1,
      8, 15 every 4 weeks followed by gemcitabine 1.0 g/m2 day 1, 8, 15 every 4 weeks;
      group CG(n=26): carboplatin AUC 2.0 and gemcitabine 0.8 g/m2 day 1, 8 every 3
      weeks followed by docetaxel 60 mg/m2 day 1, 8 every 3 weeks. RESULTS: The
      response rate of the first line therapy was 18.0% in group CP and 21.7% in group
      CG and that of the second line therapy was 10.0% and 14.3%, respectively. Time to
      progression of the first line therapy was 4.0 months in group CP and 4.3 months
      in group CG, that of the second line therapy was 2.1 months and 2.8 months,
      respectively. The median survival time was 10.9 months in group CP and 10.3
      months in group CG. No statistically significant differences were documented in
      the response rate, time to progression, and overall survival between these two
      groups. Severe hematologic toxicity was rare in both groups and no symptomatic
      peripheral neuropathy was documented in carboplatin/paclitaxel therapy.
      CONCLUSION: Carboplatin /paclitaxel followed by gemcitabine and
      carboplatin/gemcitabine followed by docetaxel were well tolerated and equal in
      efficacy. Both regimens in this study seemed to be suitable for the outpatient
      settings because of their mild hematologic toxicity and peripheral neuropathy.

PMID- 18633252
TI  - [Efficacy of 5-FU hepatic arterial infusion with l-leucovorin for patients with
      unresectable colorectal liver metastasis].
AB  - We investigated the efficacy of 5-FU hepatic artery infusion (HAI)for patients
      with unresectable colorectal liver metastasis. Fifteen patients who received HAI
      between June 2004 and December 2006 were studied. HAI was attempted as first-line
      chemotherapy in seven patients(Group A)and as second-line or more in eight(Group
      B). The response rate, time to progression, survival and toxicity were compared
      with those of 39 patients treated with systemic chemotherapy(18 as first-line:
      Group C, 21 as second-line or more: Group D). Response rate was 85.7%, 35.7%,
      50.0%, and 4.8% in Groups A, B, C, and D, respectively. Time to progression was
      12.5 months, 4.7 months, 5.8 months, and 2.3 months, in Groups A, B, C, and D,
      respectively, and significantly longer in Group A compared with Group C, as well
      as in Group B compared with Group D. Median survival was 15.4 months, 9.1 months,
      11.3 months, and 8.0 months in Groups A, B, C, and D, respectively, and
      significantly longer in Group B compared with Group D. Grade 3 or 4 non
      hematological toxicity was not observed in Group A and B. HAI was effective for
      the control of unresectable colorectal liver metastasis and improved survival as
      second-line chemotherapy or more.

PMID- 18633253
TI  - [Predictive value of orotate phosphoribosyltransferase in chemoresistant patients
      with gastric carcinoma who underwent S-1-based neoadjuvant/adjuvant
      chemotherapy].
AB  - S-1, a most effective DPD-inhibitory fluoropyrimidine, used as
      neoadjuvant/adjuvant chemotherapy has recently been shown to improve clinical
      outcome in patients with stage II and III advanced stage gastric carcinoma.
      Orotate phosphoribosyltransferase(OPRTEC 2.4.2.10)is a primary enzyme involved in
      the first-step phosphorylation process of 5-fluorouracil and is an important
      enzyme that possibly enables to predict sensitivity to S-1 irrespective of tissue
      DPD levels. To test the hypothesis that a low OPRT level in gastric carcinoma
      tissue is an indicator of chemoresistance to S-1-based chemotherapy, the
      predictive value of OPRT levels in chemoresistance was evaluated in patients with
      gastric carcinoma undergoing S-1-based-neoadjuvant/adjuvant chemotherapy using
      survival analyses. A total of 67 patients with advanced-stage gastric carcinoma
      who underwent S-1-based neoadjuvant/adjuvant chemotherapy were subjected to the
      study. The OPRT level was determined by an enzyme-linked immunosorbent
      assay(ELISA)that has recently been developed. Postoperative cumulative survival
      rates were determined by the Kaplan-Meier method. The patients who underwent S-1
      based adjuvant/neoadjuvant chemotherapy(n=67)were divided into 2 groups using
      various cut-off values to determine the prognostic significance of the OPRT
      level. The prognostic significance of OPRT levels was analyzed using Cox's
      proportional hazard model. The P value of the survival rate between the groups of
      low and high OPRT levels was the lowest(p=0.0018), when 2.0 ng/mg protein was
      used as a cut-off value for the OPRT level. The 3-year survival rate of Group L
      and Group H was 0% and 60%, respectively. In particular, there was a significant
      difference in the survival rates between Group L and Group H in stage III
      patients(p<0.05 by logrank test). T he survival rate of Group L(OPRT<2.0 ng/mg
      protein)was significantly lower than that of group H(OPRT> or =2.0 ng/mg
      protein)(p<0.05 by logrank test). The multivariate analysis using Cox'
      proportional hazard model indicated that venous invasion of carcinoma(>v2), lymph
      node metastasis(>5), and low OPRT level (OPRT<2.0 ng/mg protein) were significant
      prognostic factors in patients who were underwent S-1-based neoadjuvant/adjuvant
      chemotherapy. These results suggest that patients with a low OPRT level(OPRT<2.0
      ng/mg protein)are non-responders to S-1- based adjuvant/neoadjuvant chemotherapy.
      The determination of OPRT levels in gastric carcinoma tissue enables to predict
      the response to S-1-based neoadjuvant/adjuvant chemotherapy.

PMID- 18633254
TI  - [A pilot study of rebamipide-gargle for chemoradiotherapy-induced mucositis in
      oral cancer patients].
AB  - BACKGROUND: Mucositis induced by chemoradiotherapy is one of the serious side
      effects of cancer therapy for oral cancer. It is caused by toxic free
      radicals(activated oxygen)produced by these therapeutic modalities. Rebamipide is
      a novel anti-ulcer drug which possesses various cytoprotective activities such as
      free radical scavenging, induction of prostaglandin-E and acceleration of ulcer
      healing. We report the results of a pilot study on rebamipidegargle for
      inhibition of mucositis induced by chemo-radiotherapy. METHOD: The present study
      was conducted on 13 patients(7 men and 6 women; age range 53-88)with oral cancer.
      They received radiotherapy(30-60 Gy)for the oro-facial area and
      chemotherapy(docetaxel: 11 cases; UFT: 1 case; radiotherapy alone: 1 case)with
      simultaneous addition of 1% rebamipidegargle treatment(10-15 times/day)to prevent
      the onset of mucositis. Informed consent was obtained prior to entry. RESULTS:
      Nine cases had grade 1-2 according to the WHO criteria, and 4 patients were
      classified as grade 3-4. No adverse reactions that could be caused by the
      rebamipide gargle were observed. CONCLUSIONS: These results suggested that
      rebamipide gargle could inhibit the occurrence of stomatitis induced by
      chemoradiotherapy.

PMID- 18633255
TI  - [Bolus injection of vinorelbine reduces incidence of local venous toxicity in
      patients with non-small cell lung cancer and breast cancer].
AB  - Vinorelbine is currently considered as one of the most active chemotherapeutic
      agents for non-small cell lung cancer and breast cancer. On the other hand, it is
      known as a vesicant drug frequently inducing venous irritation and phlebitis.
      Although the manufacturer's instructions recommend drip infusion for the drug
      administration in Japan, in 5 to 30% of patients venous toxicity has been
      reported that sometimes leads to treatment discontinuation even if it brings
      about a favorable response. In this report, we describe a retrospective study
      that compares drip infusion and bolus injection to prevent local venous toxicity.
      Seventy-one drip infusions and 196 bolus injections were administered to 18 and
      40 non-small cell lung cancer patients, respectively. Also, 124 drip infusions
      and 335 bolus injections were administered to 13 and 38 breast cancer patients,
      respectively. We found that the bolus injection significantly reduced the
      incidence of vinorelbine- induced local venous toxicity in both diseases(22.2%
      versus 0% in non-small cell lung cancer patients, p<0.0006, and 46.2% versus 7.9%
      in breast cancer patients, p<0.0001). Our study demonstrates that bolus injection
      of vinorelbine is a suitable way for safe chemotherapy especially in an
      outpatient setting.

PMID- 18633256
TI  - [The efficacy and safety of indisetron hydrochloride for the management of
      nausea/vomiting caused by chemotherapy for gynecologic cancer].
AB  - This clinical trial was designed to evaluate the efficacy and safety of
      indisetron hydrochloride an oral 5-HT3 receptor antagonist, for the management of
      nausea/vomiting caused by chemotherapy for gynecologic cancer with paclitaxel/
      carboplatin or docetaxel/carboplatin. Indisetron hydrochloride(8 mg)was
      administered orally to 46 gynecologic cancer patients at 0.5 hours before
      administration of the above chemotherapy agents. Number of patients who showed
      nausea or vomiting for 24 hours was counted. The complete vomiting inhibition
      rate at 24 hours after chemotherapy was 89.1%(41/46), and nausea inhibition rate
      was 71.7%(33/46). No serious adverse events were observed. These findings
      indicate that prophylactic administration of indisetron hydrochloride is safe and
      useful for inhibition of nausea/vomiting caused by cancer chemotherapy.

PMID- 18633257
TI  - [Comparative survey on current status and the differences of treatment using
      modified FOLFOX6 regimen in patients with colorectal cancer in two general
      hospitals].
AB  - We surveyed the current status and the differences of treatment of colorectal
      cancer using modified FOLFOX6 regimen, in two general hospitals, Sakai City
      Hospital (A hospital) and Takarazuka Municipal Hospital (B hospital) between
      April 2005 and November 2006, retrospectively. The numbers of examined patients
      were 33 and 17 in A and B hospitals, respectively. The grade of myelosuppression
      and peripheral neuropathy were evaluated according to Common Terminology Criteria
      for Adverse Events v 3.0(CTCAE v 3.0)and Neurotoxicity Criteria of DEBIOPHARM(DEB
      NTC). The setting of dosage was differed in two hospitals. In A hospital, the
      dosages of oxaliplatin, 5-FU bolus and 5-FU continuous infusion were more than
      90% of the standard one at first time, and were reduced with almost same degree
      in the appearance of adverse effects. On the other hand, in B hospital, the
      dosages of these drugs were reduced about 20% even at first administration and,
      especially, the dose of 5-FU bolus tended to be remarkable reduction. Of adverse
      events, the rates of the appearance of neutropenia more than grade 3 was 21.2%
      and 47.1%, in A and B hospitals, respectively. No difference in peripheral
      neuropathy was detected at both hospitals. In conclusion, the differences in
      these two hospitals were detected in the dosage setting and myelosuppression, not
      in non-hematological adverse effects.

PMID- 18633258
TI  - [A case report of S-1 single effective use as third-line chemotherapy and re
      challenge in a recurrent squamous cell lung cancer patient].
AB  - CASE: A 72-year-old male had suffered from a recurrent pulmonary squamous cell
      carcinoma. He had a history of systemic chemotherapy including
      carboplatin+paclitaxel(CBDCA+PTX)and docetaxel(DOC). As third-line chemotherapy,
      this patient was treated with 100 mg of S-1 daily for 4 weeks followed by 2 weeks
      of rest. Maximal effect was acquired 3.5 months after start of S-1 and resulted
      in partial response. Since tumors re-grew, S-1 was stopped and other
      chemotherapies including gemcitabine+vinorelbine(GEM+VNR)and gefitinib were tried
      but proved ineffective. The tumors gradually grew and, subsequently, right total
      atelectasis occurred. Re-administration of S-1 showed tumor regression and
      atelectasis improved. Now this patient is continuing treatment with S-1
      monotherapy.

PMID- 18633259
TI  - [Long survival of advanced gastric cancer patient after total gastrectomy and
      postoperative treatment with S-1 despite S-1+CDDP+CPT-11 causing perforation].
AB  - Here we report a rare case with perforation of gastric cancer responding to
      chemotherapy. The patient was a 74- year-old male who underwent abdominal
      ultrasonography and contrast CT because of body-weight lost and poor appetite in
      June, 2004 and whose lymph node(LN)swelling was seen in the level from the
      hepatic to the renal hilum. A gastric wall irregularity was also seen. We
      suspected gastric cancer with LN metastasis and carried out upper
      gastrointestinal endoscopy. Then it demonstrated type 2 advanced gastric cancer
      from the upper to the middle body. The pathological diagnosis of gastric tumor
      was poorly-differentiated adenocarcinoma containing por 2, tub 1, and pap. The
      patient was treated with S-1, CDDP and CPT-11 and remained ambulant. After
      completion of 1 course of chemotherapy, he complained of intense abdominal pain,
      so we carried out upper gastrointestinal endoscopy and found perforation in the
      stomach at the same location as the gastric cancer. Emergency total gastrectomy
      was performed at once. The histopathological finding showed disappearance of the
      cancer cell not only in the stomach but also accessory LN. Because the remnant LN
      metastasis was seen in the hepatic hilum at abdominal contrast CT after
      operation, S-1 was administered to the patient as 60 mg/m2/day in ambulant. Now,
      over 40 months after the operation, the patient has been alive with good
      performance status and disappearance of LN metastasis.

PMID- 18633260
TI  - [Pathological complete response in an elderly patient with locally advanced
      gastric cancer treated with S-1/CDDP].
AB  - We report a patient with locally advanced gastric carcinoma successfully treated
      with S-1/CDDP. The patient was a 77-year-old woman who had gastric cancer
      surgically diagnosed as T4N2, invading the pancreas and mesocolon. After the
      firsts exploratory laparotomy, chemotherapy was begun as follows. S-1(80
      mg/day)was orally administered for 3 weeks followed by 2 weeks' rest as a course,
      and CDDP(75 mg/body)was administered by intravenous drip on day 8. Because of
      severe anorexia and nausea, however, the CDDP administration had to be
      discontinued. Therefore, we changed the procedure to S-1 single treatments, 2
      weeks' administration followed by 2 weeks' rest. The total 9 courses of this
      procedure proved successful. Subsequently, she underwent curative surgery
      consisting of total gastrectomy with D2 lymph node dissection, combined with
      distal pancreatectomy and splenectomy, and obtained pathological CR. S-1/CDDP
      appears to be an effective treatment modality for advanced gastric cancer.

PMID- 18633261
TI  - [A case of Stage IV gastric cancer with liver and peritoneal metastases
      responding completely to tailored S-1/CPT- 11 combination therapy].
AB  - A 75-year-old man with advanced gastric cancer underwent distal gastrectomy with
      lymph node dissection(D1)and Roux-en Y reconstruction. Pathological staging was
      Stage IV (T3N3P1CY1M1), and curability was Cur C. He started adjuvant
      chemotherapy with oral administration of S-1(100 mg/body weight), but experienced
      grade 3 anorexia for one month. Abdominal computed tomography(CT)2 months
      postoperatively showed multiple liver metastases and ascites. We then conducted
      tailored S-1/CPT-11 as second-line chemotherapy(S-1 80 mg/body weight on days 1-5
      and 8-12, CPT-11 60 mg/body weight on days 1 and 8). After 5 courses of this
      therapy, CT showed that the liver metastases and ascites had disappeared, leading
      to a complete response(CR). The only adverse event was general grade 1 fatigue.
      He continues to undergo oral administration of S-1(80 mg/body weight)as
      maintenance therapy, and maintained CR for 12 months since undergoing
      chemotherapy. Adverse events in tailored S-1/CPT-11 combination therapy are mild
      and tolerable, making this regimen a potential therapeutic strategy for patients
      with advanced or recurrent gastric cancer.

PMID- 18633262
TI  - [A case of advanced gastric cancer with multiple liver metastases completely
      responding to combination of paclitaxel and S-1].
AB  - A 46-year-old female was admitted to Kagoshima University Hospital with a
      complaint of epigastralgia and dysphasia. Gastrointestinal scopy revealed
      advanced gastric cancer in the upper third of the stomach. Pathological diagnosis
      of the biopsy specimen was moderately-differentiated adenocarcinoma. Abdominal CT
      suggested multiple liver metastases, so a combination of biweekly
      paclitaxel(PTX)and S-1 was started. After five courses of this regimen, the liver
      metastases and primary tumor were remarkably regressed. PTX was discontinued
      because of a grade 3 adverse effect of numbness. Nevertheless S-1 monotherapy for
      liver metastases resulted in a complete response. She has been well without tumor
      re-growth for 4 years. The combination of PTX and S-1 may be an effective regimen
      for gastric cancer with liver metastases.

PMID- 18633263
TI  - [A case of disseminated bone marrow carcinosis with disseminated intravascular
      coagulation successfully controlled with S-1 after total gastrectomy for advanced
      gastric cancer].
AB  - Bone marrow carcinosis due to gastric cancer with disseminated intravascular
      coagulation(DIC)occurs suddenly, progresses rapidly, and has a very poor
      prognosis. In addition, physical status tends to be bad at the time of the
      episode, and palliative care is generally selected as the treatment method. The
      case was a 70-year-old woman who underwent total gastrectomy for scirrhous
      stomach cancer five years previously. She recently noticed gingival hemorrhage,
      and was referred to our hospital by a nearby doctor. As a result of her
      examination, she was diagnosed with disseminated bone marrow carcinosis as a
      postoperative recurrence of gastric cancer that resulted in DIC. We transfused
      blood platelets and fresh frozen plasma into her, and controlled the bleeding
      tendency temporarily. She was started on oral administration of S-1 for
      improvement of DIC, and the therapy was successful without loss of QOL. It is
      easy to continue S-1 therapy as chemotherapy in the outpatient department,
      because it is a matter of internal medicine.

PMID- 18633264
TI  - [A patient in whom oral UFT/Leucovorin therapy proved markedly effective for lung
      metastasis after surgery for colon cancer].
AB  - A 78-year-old male with sigmoid colon cancer underwent sigmoidectomy. The lesion
      was se, p1(+), n1, and Stage IV. Oral UFT therapy was performed, but was replaced
      with oral S-1 therapy 1 year and 6 months after surgery. Three months later, lung
      metastases 2.0 x 1.5 cm and 0.6 x 0.6 cm were found by chest CT in right S10a and
      S5b, respectively. Since the patient did not wish surgery, the treatment was
      changed to oral UFT/Leucovorin(LV)therapy(UFT 300 mg/ LV 75 mg, 4-week
      administration and 1-week no-administration periods). After 2 courses, chest CT
      showed disappearance of both lung metastases, indicating complete remission. Oral
      UFT/LV therapy is convenient because of the oral route. Adverse reactions are
      few, and the therapeutic effect has been reported to be comparable to that of
      intravenous 5-FU/LV therapy. Also, in this patient, no adverse reaction was
      noted, and complete remission was maintained until the patient died of another
      disease 31 months after the beginning of oral UFT/LV therapy.

PMID- 18633265
TI  - [Combination chemotherapy composed of mFOLFOX 6, FOLFIRI 2 and surgery and
      radiation therapy for locoregional recurrences and multiple lung metastases from
      rectal cancer--a case report].
AB  - A 61-year-old man underwent amputation of the rectum for advanced lower rectal
      cancer in April 2005. UFT-E granules were administered orally daily at 400
      mg/body/day following surgery. He developed perineal pain and perineal discharges
      following an increase the CEA level in April 2006. PET revealed a tumor in the
      perineum and multiple lung metastases. Chemotherapy with mFOLFOX 6 for 8 courses
      and FOLFIRI 2 for 4 courses were administered since July in 2006. Although CT
      revealed a the reduction in multiple lung metastases, CEA was increased to over a
      maximum 109, high fever continued and the pinealtumor was enlarged in December
      2006. The patient underwent resection of the perinealmass, but he developed
      perinealsevere pain and perinealdischarge. So radiotherapy of the pelvic region
      was given at a total dose of 40 Gy(given 2 Gy each fragment)followed by
      administration of FOLFIRI 2 for 12 courses. After chemoradiotherapy, the CEA
      level was remarkably decreased. PET could not detect any mass in lung fields and
      revealed a little accumulation in the pelvic region. Chemotherapy with FOLFIRI 2
      is administered monthly now, and the CEA level has been within the normal range
      since July of 2007. The pineal pain and pineal discharge disappeared, so the
      quality of life has improved dramatically.

PMID- 18633266
TI  - [5-FU/LV therapy for a rectal cancer patient undergoing continuous hemodialysis
      with multiple hepatic metastases--a case report].
AB  - Chemotherapy for advanced or recurrent colorectal cancer is standardized as
      oxaliplatin/5-FU/LV therapy (FOLFOX)and irinotecan/5-FU/LV therapy(FOLFIRI). It
      is difficult to introduce cancer chemotherapy to hemodialysis patients, and
      limited chemotherapeutics are available. The case was a 57-year-old man who was
      undergoing continuous hemodialysis when rectal cancer was found with multiple
      hepatic metastases. After rectum elevation and anterior resection, we treated him
      with 5-FU/LV therapy. After three courses the number of hepatic metastatic foci
      decreased, and the ascites disappeared. Levels of carcinoembryonic
      antigen(CEA)decreased from 837 ng/mL to 29 ng/mL; carbohydrate antigen 19-9(CA19
      9)decreased from 79.6 U/mL to 14.2 U/mL, and cancer-related antigen 72-4 (CA72
      4)was reduced from 33.3 U/mL to 7.4 U/mL. Partial remission was achieved
      following the chemotherapy. We used 5-FU/LV therapy according to the Roswell Park
      Memorial Institute method. Our patient was able to undergo treatment safely
      without serious adverse drug response, except that he exhibited diarrhea and hand
      foot syndrome of grade 2.

PMID- 18633267
TI  - [A case of peritoneal disseminated sigmoid colon cancer with liver metastasis
      responding to S-1].
AB  - In October 2004, a 73-year-old man underwent loop ileostomy because of
      unresectable peritoneal disseminated sigmoid colon cancer with liver metastasis.
      The oral chemotherapy by S-1 was administered(80 mg/day for 4 weeks followed by a
      2-week rest period). A half year later, the primary lesion was remarkably
      diminished on barium enema, and peritoneal dissemination and liver metastasis
      disappeared on CT. Because he was unwilling to have an ileostomy, we decided to
      resect the primary lesion and close the ileal stoma in May 2005. There was no
      obvious peritoneal dissemination, and operation was successful. He died without
      intestinal stoma one year after second operation. This therapy can be orally
      administered at home, and is considered to be useful from the viewpoint of QOL as
      well. S-1 is expected to be an effective agent for the treatment of colon cancer.

PMID- 18633268
TI  - [A case of simultaneous hepatic metastases of ascending colon cancer responding
      completely to tegafur/uracil plus oral Leucovorin therapy after primary lesion
      resection].
AB  - An 81-year-old woman, who suffered from ascending colon cancer with liver
      metastases, underwent right hemicolectomy. She did not undergo liver resection
      due to her age and her family's decision, and was treated with UFT plus oral
      Leucovorin therapy. The metastases were remarkably reduced in the early phase and
      disappeared completely on SPIO-MRI 2 years 9 months later. Adverse effects of
      this therapy are relatively few, and it can serve as first-line chemotherapy for
      advanced colorectal cancer.

PMID- 18633269
TI  - [A case of peritoneal dissemination caused by recurrent hilar cholangiocarcinoma
      treated with intraperitoneal infusion of cisplatin (CDDP) and systemic
      chemotherapy].
AB  - Six years and 9 months ago, a 72-year-old man underwent left hepatectomy for a
      hilar cholangiocarcinoma(T2N0M0: Stage II A). At 3 years and 2 months after
      surgery, he was admitted for rectal tumor and reoperation. From surgery, it was
      diagnosed as peritoneal metastases of the cholangiocarcinoma, and an
      intraperitoneal infusion port was placed. He was treated with gemcitabine
      administered iv at day 1 and CDDP ip at day 8 every 3 or 4 weeks for 2 years.
      Then, gemcitabine was changed to docetaxel because of elevation of CA19-9. Both
      docetaxel iv and CDDP ip were administered for one and half years. For 3 years
      and 4 months, 12.2 g of CDDP, 28.0 g of gemcitabine and 920 mg of docetaxel were
      administered. As serum CA19-9 elevated again, he has been treated with S-1 and
      docetaxel ip for 3 months. This case indicates that intraperitoneal application
      of CDDP with systematic chemotherapy was effective for carcinomatous peritonitis
      without serious side effects.

PMID- 18633270
TI  - [Chemotherapy with gemcitabine after non-curative resection of bile duct cancer-
      a case report].
AB  - Non-curative resection for cholangiocarcinoma usually leads to a poor prognosis.
      We present a case successfully treated with gemcitabine for residual tumor after
      extra hepatic bile duct resection with positive surgical margin. The patient was
      a 77-year-old male who was diagnosed as having a common bile duct cancer. Extra
      hepatic bile duct resection was performed, but intraoperative pathology diagnosed
      the surgical margin of duodenal-side bile duct was positive for cancer. Although
      additional resection of bile duct was done, pathological diagnosis resulted in
      positive margin again. We had to avoid pancreatoduodenectomy in light of the
      patient's wishes, so a curative resection could not be carried out. Adjuvant
      chemotherapy with gemcitabine(800 mg/m2 on days 1, 8 and 15 every 4 weeks)was
      started at the seventh postoperative day. A residual lesion was shown in the
      pancreas head by abdominal CT after 2 courses of chemotherapy. Follow-up CT was
      performed every 6 months, and the lesion gradually seemed to become unclear.
      Finally, CT showed disappearance of the residual lesion 28 months after surgery.
      The chemotherapy has been continued up to the present(3 years and 5 months after
      surgery). No evidence of recurrence nor adverse events of WHO grade 2 or more has
      been observed.

PMID- 18633271
TI  - [Usefulness of S-1/gemcitabine combination therapy for advanced pancreatic
      cancer].
AB  - Combination chemotherapy with S-1 and gemcitabine(GEM)was given to patients with
      advanced pancreatic cancer and favorable results were obtained. These patients
      were 77-(Stage IVa), 68-(Stage IVb), and 64-year-old males (Stage IVb). They were
      administered S-1 at a dose of 80-100 mg/day for 2 weeks and GEM at a dose of
      1,000-1,200 mg/body on days 8 and 15 followed by a 2-week recovery period. One
      course consisted of a 2-week treatment period and a recovery period; this course
      was repeated in all of these patients. The 3 types of patients have survived for
      a year and five months, a year and three months, and nine months, respectively,
      after diagnosis. In the first patient, who was in Stage IVa, the primary cancer
      has been maintained in a reduced state without metastasis. In the other two
      patients, who were in Stage IVb, the primary cancer and hepatic metastatic
      lesions have been reduced remarkably. Quality of life is good in all the
      patients. Combination therapy with S-1 and GEM can be provided for a long-term
      treatment with few adverse reactions on an outpatient basis. Based on the changes
      in tumor markers, we observed that the inhibitory effects of this combination
      chemotherapy are immediate and persistent with long-term treatment. Therefore, we
      expect S-1/GEM combination therapy to be the chemotherapy of choice for advanced
      pancreatic cancer.

PMID- 18633272
TI  - [A case of advanced pancreatic cancer successfully treated by combined
      chemotherapy of S-1 and gemcitabine].
AB  - The patient was a 71-year-old woman. In March of 2007, she experienced abdominal
      pain, and consulted a physician at our hospital. She was followed on a outpatient
      basis, but the symptom did not improve, so she consulted our division. As a
      result of examinations, pancreatic head tumor, multiple liver metastasis, and
      para-aortic lymph node swelling were detected. She was then admitted for
      chemotherapy in our hospital. She was treated with combined chemotherapy of S-1
      and GEM. Tumor marker(CEA, CA19-9)decreased and the size of the pancreatic head
      tumor and liver metastasis decreased. No toxic events were observed due to this
      therapy. She was treated as an outpatient, and was considered to have good
      quality of life.

PMID- 18633273
TI  - [A case of brain metastasis from advanced ovarian clear-cell carcinoma during
      maintenance chemotherapy with irinotecan+cisplatin].
AB  - Clear-cell carcinoma of the ovary is a highly malignant neoplasm. Survival of
      patients in the advanced stage is poor, and the best treatment is not clear. We
      report here a case of a 57-year-old woman who had Stage IIIb advanced clearcell
      carcinoma of the ovary. We performed abdominal hysterectomy, bilateral salpingo
      oophorectomy, pelvic lympho adenectomy and partial omentectomy. After the
      operation she was placed on induction and maintenance chemotherapy with a
      combination of irinotecan(CPT-11)(60 mg/m2, day 1, 15)plus cisplatin(CDDP)(60
      mg/m2, day 1). Four years after surgery, a metastatic tumor was found in the
      brain. Considering the poor prognosis of clear-cell carcinoma, this regimen is
      thought to be effective for advanced clear-cell carcinoma of the ovary. It is
      important to check brain metastases under maintenance chemotherapy.

PMID- 18633274
TI  - [A case of hormone/docetaxel-refractory prostate cancer in which PSA level
      decreased after docetaxel+zoledronic acid treatment].
AB  - The patient was a 63-year-old man who had a recurrence and bone metastasis of
      prostate cancer after total prostatectomy. He was diagnosed with prostate cancer
      refractory to hormones. Subsequently, the PSA level decreased after docetaxel
      therapy, but then gradually increased. Thus, he was diagnosed with bone
      metastasis of prostate cancer refractory to therapy with hormones or docetaxel.
      The PSA level decreased after the start of therapy with docetaxel+ zoledronic
      acid. Zoledronic acid seems to be effective not only for the prevention but also
      for the treatment of skeletal related events(SRE)in patients with prostate cancer
      with bone metastases.

PMID- 18633275
TI  - Bacterial and fungal communities in bulk soil and rhizospheres of aluminum
      tolerant and aluminum-sensitive maize (Zea mays L.) lines cultivated in unlimed
      and limed Cerrado soil.
AB  - Liming of acidic soils can prevent aluminum toxicity and improve crop production.
      Some maize lines show aluminum (Al) tolerance, and exudation of organic acids by
      roots has been considered to represent an important mechanism involved in the
      tolerance. However, there is no information about the impact of liming on the
      structures of bacterial and fungal communities in Cerrado soil, nor if there are
      differences between the microbial communities from the rhizospheres of Al
      tolerant and Al-sensitive maize lines. This study evaluated the effects of liming
      on the structure of bacterial and fungal communities in bulk soil and
      rhizospheres of Al-sensitive and Al-tolerant maize (Zea mays L.) lines cultivated
      in Cerrado soil by PCR-DGGE, 30 and 90 days after sowing. Bacterial fingerprints
      revealed that the bacterial communities from rhizospheres were more affected by
      aluminum stress in soil than by the maize line (Al-sensitive or Al-tolerant).
      Differences in bacterial communities were also observed over time (30 and 90 days
      after sowing), and these occurred mainly in the Actinobacteria. Conversely,
      fungal communities from the rhizosphere were weakly affected either by liming or
      by the rhizosphere, as observed from the DGGE profiles. Furthermore, only a few
      differences were observed in the DGGE profiles of the fungal populations during
      plant development when compared with bacterial communities. Cloning and
      sequencing of 16S rRNA gene fragments obtained from dominant DGGE bands detected
      in the bacterial profiles of the Cerrado bulk soil revealed that Actinomycetales
      and Rhizobiales were among the dominant ribotypes.

PMID- 18633276
TI  - Application of rDNA-PCR amplification and DGGE fingerprinting for detection of
      microbial diversity in a Malaysian crude oil.
AB  - Two culture-independent methods, namely ribosomal DNA libraries and denaturing
      gradient gel electrophoresis (DGGE), were adopted to examine the microbial
      community of a Malaysian light crude oil. In this study, both 16S and 18S rDNAs
      were PCR-amplified from bulk DNA of crude oil samples, cloned, and sequenced.
      Analyses of restriction fragment length polymorphism (RFLP) and phylogenetics
      clustered the 16S and 18S rDNA sequences into seven and six groups, respectively.
      The ribosomal DNA sequences obtained showed sequence similarity between 90 to
      100% to those available in the GenBank database. The closest relatives documented
      for the 16S rDNAs include member species of Thermoincola and Rhodopseudomonas,
      whereas the closest fungal relatives include Acremonium, Ceriporiopsis,
      Xeromyces, Lecythophora, and Candida. Others were affiliated to uncultured
      bacteria and uncultured ascomycete. The 16S rDNA library demonstrated
      predomination by a single uncultured bacterial type by >80% relative abundance.
      The predomination was confirmed by DGGE analysis.

PMID- 18633277
TI  - Identification and characterization of a new strain of the unicellular green alga
      Dunaliella salina (Teod.) from Korea.
AB  - The unicellular green alga Dunaliella salina is a halotolerant eukaryotic
      organism. Its halophytic properties provide an important advantage for open pond
      mass cultivation, since D. salina can be grown selectively. D. salina was
      originally described by E. C. Teodoresco in 1905. Since that time, numerous
      isolates of D. salina have been identified from hypersaline environments on
      different continents. The new Dunaliella strain used for this study was isolated
      from the salt farm area of the west coastal side of South Korea. Cells of the new
      strain were approximately oval- or pear-shaped (approximately 16-24 microm long
      and 10-15 microm wide), and contained one pyrenoid, cytoplasmatic granules, and
      no visible eyespot. Although levels of beta-carotene per cell were relatively low
      in cells grown at salinities between 0.5 to 2.5 M NaCl, cells grown at 4.5 M NaCl
      contained about a ten-fold increase in cellular levels of beta-carotene, which
      demonstrated that cells of the new Korean strain of Dunaliella can overaccumulate
      beta- carotene in response to salt stress. Analysis of the ITS1 and ITS2 regions
      of the new Korean isolate showed that it is in the same clade as D. salina.
      Consequently, based on comparative cell morphology, biochemistry, and molecular
      phylogeny, the new Dunaliella isolate from South Korea was classified as D.
      salina KCTC10654BP.

PMID- 18633278
TI  - Positive regulation of pyoluteorin biosynthesis in Pseudomonas sp. M18 by quorum
      sensing regulator VqsR.
AB  - The biocontrol rhizobacterium Pseudomonas sp. M18 can produce two kinds of
      antibiotics, namely pyoluteorin (Plt) and phenazine-1-carboxylic acid (PCA), and
      is antagonistic against a number of soilborne phytopathogens. In this study, a
      luxR-type quorum-sensing regulatory gene, vqsR, was identified and characterized
      immediately downstream of the Plt gene cluster in strain M18. A vqsR-inactivated
      mutant led to a significant decrease in the production of Plt and its
      biosynthetic gene expression. However, this was restored when introducing the
      vqsR gene by cloning into the plasmid pME6032 in trans. The vqsR mutation did not
      exert any obvious influence on the production of PCA and its biosynthetic gene
      expression and the production of Nacylhomoserine lactones (C4 and C8-HSLs) and
      their biosynthetic gene rhlI expression. Accordingly, these results introduce
      VqsR as a regulator of Plt production in Pseudomonas spp., and suggest that the
      regulatory mechanism of vqsR in strain M18 is distinct from that in P.
      aeruginosa. In addition, it was demonstrated that vqsR mutation did not have any
      obvious impact on the expression of Plt-specific ABC transporters and other
      secondary metabolic global regulators, including GacA, RpoS, and RsmA.

PMID- 18633279
TI  - Deletion of xylR gene enhances expression of xylose isomerase in Streptomyces
      lividans TK24.
AB  - Glucose (xylose) isomerases from Streptomyces sp. have been used for the
      production of high fructose corn syrup for industrial purposes. An 11-kb DNA
      fragment containing the xyl gene cluster was isolated from Streptomyces lividans
      TK24 and its nucleotide sequences were analyzed. It was found that the xyl gene
      cluster contained a putative transcriptional repressor (xylR), xylulokinase
      (xylB), and xylose isomerase (xylA) genes. The transcriptional directions of the
      xylB and xylA genes were divergent, which is consistent to those found in other
      streptomycetes. A gene encoding XylR was located downstream of the xylB gene in
      the same direction, and its mutant strain produced xylose isomerase regardless of
      xylose in the media. The enzyme expression level in the mutant was 4.6 times
      higher than that in the parent strain under xylose-induced condition. Even in the
      absence of xylose, the mutant strain produce over 60% of enzyme compared with the
      xylose-induced condition. Gel mobility shift assay showed that XylR was able to
      bind to the putative xyl promoter, and its binding was inhibited by the addition
      of xylose in vitro. This result suggested that XylR acts as a repressor in the S.
      lividans xylose operon.

PMID- 18633280
TI  - Expression and biochemical characterization of the periplasmic domain of
      bacterial outer membrane porin TdeA.
AB  - TolC is an outer membrane porin protein and an essential component of drug efflux
      and type-I secretion systems in Gram-negative bacteria. TolC comprises a
      periplasmic alpha- helical barrel domain and a membrane-embedded beta-barrel
      domain. TdeA, a functional and structural homolog of TolC, is required for toxin
      and drug export in the pathogenic oral bacterium Actinobacillus
      actinomycetemcomitans. Here, we report the expression of the periplasmic domain
      of TdeA as a soluble protein by substitution of the membraneembedded domain with
      short linkers, which enabled us to purify the protein in the absence of
      detergent. We confirmed the structural integrity of the TdeA periplasmic domain
      by size-exclusion chromatography, circular dichroism spectroscopy, and electron
      microscopy, which together showed that the periplasmic domain of the TolC protein
      family can fold correctly on its own. We further demonstrated that the
      periplasmic domain of TdeA interacts with peptidoglycans of the bacterial cell
      wall, which supports the idea that completely folded TolC family proteins
      traverse the peptidoglycan layer to interact with inner membrane transporters.

PMID- 18633281
TI  - Purification and cloning of an extracellular serine protease from the nematode
      trapping fungus Monacrosporium cystosporium.
AB  - An extracellular protease (Mc1) was isolated from the nematode-trapping fungus
      Monacrosporium cystosporium by gel filtration, anion-exchange, and hydrophobic
      interaction chromatographies. This protease had a molecular mass of approximately
      38 kDa and displayed an optimal activity at pH 7-9 and 56 degrees (over 30 min).
      Its proteolytic activity was highly sensitive to the serine protease inhibitor
      PMSF (phenylmethylsulfonylfluoride, 0.1 mM), indicating that it belonged to the
      serine-type peptidase group. The Michaelis constant (Km) and Vmax for substrate N
      Suc-Ala-Ala-Pro-Phe-pNA were 1.67x10-4 M and 0.6071 OD410 per 30 s, respectively.
      This protease could degrade a broad range of substrates including casein,
      gelatin, BSA (bovine serum albumin), and nematode cuticle. Moreover, the enzyme
      could immobilize the free-living nematode Panagrellus redivivus and the pine wood
      nematode Bursaphelenchus xylophilus, suggesting that it might play a role in
      infection against nematodes. The encoding gene of Mc1 was composed of one intron
      and two exons, coding for a polypeptide of 405 amino acid residues. The deduced
      amino acid sequence of Mc1 showed 61.4-91.9% identity to serine proteases from
      other nematode-trapping fungi. Our results identified that Mc1 possessed
      biochemical properties including optimal reaction condition and substrate
      preference that are different from previously identified serine proteases.

PMID- 18633282
TI  - Biochemical characterization of a glycosyltransferase homolog from an oral
      pathogen Fusobacterium nucleatum as a human glycan-modifying enzyme.
AB  - Bacterial glycosyltransferases have drawn growing attention as economical enzymes
      for oligosaccharide synthesis, with their easy expression and relatively broad
      substrate specificity. Here, we characterized a glycosyltransferase homolog
      (Fnu_GT) from a human oral pathogen, Fusobacterium nucleatum. Bioinformatic
      analysis showed that Fnu_GT belongs to the glycosyltransferases family II. The
      recombinant Fnu_GT (rFnu_GT) expressed in Escherichia coli displayed the highest
      glycosylation activity when UDP-galactose (Gal) was used as a donor nucleotide
      sugar with heptose or Nacetylglucosamine (GlcNAc) as an acceptor sugar.
      Interestingly, rFnu_GT transferred the galactose moiety of UDP-Gal to a
      nonreducing terminal GlcNAc attached to the trimannosyl core glycan, indicating
      its potential as an enzyme for humantype N-glycan synthesis.

PMID- 18633283
TI  - Heterologous production and detection of recombinant directing 2-deoxystreptamine
      (DOS) in the non-aminoglycoside-producing host Streptomyces venezuelae YJ003.
AB  - 2-Deoxystreptamine is a core aglycon that is vital to backbone formation in
      various aminoglycosides. This core structure can be modified to develop hybrid
      types of aminoglycoside antibiotics. We obtained three genes responsible for 2
      deoxystreptamine production, neo7, neo6, and neo5, which encode 2-deoxy-scyllo
      inosose synthase, L-glutamine: 2-deoxy-scyllo-inosose aminotransferase, and
      dehydrogenase, respectively, from the neomycin gene cluster. These genes were
      cloned into pIBR25, a Streptomyces expression vector, resulting in pNDOS. The
      recombinant pNDOS was transformed into a non-aminoglycoside-producing host,
      Streptomyces venezuelae YJ003, for heterologous expression. Based on comparisons
      of the retention time on LC-ESI/MS and ESIMS data with those of the 2
      deoxystreptamine standard, a compound produced by S. venezuelae YJ003/pNDOS was
      found to be 2-deoxystreptamine.

PMID- 18633284
TI  - Inhibitory effect of dalbergioidin isolated from the trunk of Lespedeza
      cyrtobotrya on melanin biosynthesis.
AB  - Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation
      disorders are associated with abnormal accumulation of melanin pigments, which
      can be reduced by treatment with depigmenting agents. The methanol extract of
      Lespedeza cyrtobotrya MIQ showed inhibitory activity against mushroom tyrosinase.
      The active compound was purified from the methanol extract of L cyrtobotrya,
      followed by several chromatographic methods, and identified as dalbergioidin
      (DBG) by spectroscopic methods. The results showed that DBG exhibited tyrosinase
      inhibitory activity with an IC50 of 20 mM. The kinetic analysis tyrosinase
      inhibition revealed that DBG acted as noncompetitive inhibitor. In addition, DBG
      showed a melanin biosynthesis inhibition zone in the culture plate of
      Streptomyces bikiniensis that has commonly been used as an indicator organism.
      Furthermore, 27 mM DBG decreased more than 50% of melanin contents on the
      pigmentation using immortalized mouse melanocyte, melan-a cell.

PMID- 18633285
TI  - Antifungal activity of valinomycin, a peptide antibiotic produced by Streptomyces
      sp. Strain M10 antagonistic to Botrytis cinerea.
AB  - A strain of Streptomyces sp. (M10) antagonistic to Botrytis cinerea was isolated
      from orchard soil obtained from Jeju Island, Korea. An antifungal substance (CN1)
      was purified from the culture extracts of the strain, and then identified as
      valinomycin through extensive spectroscopic analyses. Valinomycin showed potent
      in vitro antifungal activity against Botrytis cinerea and also in vivo control
      efficacy against Botrytis blight development in cucumber plants. Overall, the
      disease control efficacy of valinomycin was similar to that of vinclozolin, a
      commercial fungicide. This study provides the first report on the disease control
      efficacy of valinomycin against Botrytis blight.

PMID- 18633286
TI  - Continuous cell-free protein synthesis using glycolytic intermediates as energy
      sources.
AB  - In this work, we demonstrate that glycolytic intermediates can serve as efficient
      energy sources to regenerate ATP during continuous-exchange cell-free (CECF)
      protein synthesis reactions. Through the use of an optimal energy source,
      approximately 10 mg/ml of protein was generated from CECF protein synthesis
      reaction at greatly reduced reagent costs. Compared with the conventional
      reactions utilizing phosphoenol pyruvate as an energy source, the described
      method yields 10-fold higher productivity per unit reagent cost, making the
      techniques of CECF protein synthesis more realistic alternative for rapid protein
      production.

PMID- 18633287
TI  - Modeling of esterase production from Saccharomyces cerevisiae.
AB  - A suitable simple model tested by experiments is required to address complex
      biological reactions like esterase synthesis by Saccharomyces cerevisiae. Such an
      approach might be the answer to a proper bioprocessing strategy. In this regard,
      a logistic model for esterase production from Saccharomyces cerevisiae has been
      developed, which predicts well the cell mass, the carbon source (glucose)
      consumption, and the esterase activity. The accuracy of the model has been
      statistically examined by using the Student's t-test. The parameter sensitivity
      analysis showed that all five parameters (microm, Ks, Xm, Yx/s, and Yp/x) have
      significant influence on the predicted values of esterase activity.

PMID- 18633288
TI  - Enhancement of geldanamycin production by pH shock in batch culture of
      Streptomyces hygroscopicus subsp. duamyceticus.
AB  - Various sequences of pH change were applied in a batch bioreactor to investigate
      pH shock effects on geldanamycin production by Streptomyces hygroscopicus subsp.
      duamyceticus JCM4427. In the control culture where the pH was not controlled, the
      maximum geldanamycin concentration was 414 mg/l. With the pHS1 mode of pH shock,
      that is, an abrupt pH change from pH 6.5 to pH 5.0 and then being maintained at
      around pH 5.0 afterward, 768mg/l of geldanamycin was produced. With pHS2, in
      which the pH was changed sequentially from pH 6.7 to pH 5.0 and then back to pH
      6.0, 429 mg/l of geldanamycin was produced. With pHS3 having a sequential pH
      change from pH 6.0 to pH 4.0 and then back to pH 6.5 followed by the third pH
      shock to pH 5.5, no geldanamycin production was observed. Considering that the
      productivity with pHS1 was about two-fold of that of the control culture with no
      pH control, we concluded that a more sophisticated manipulation of pH would
      further promote geldanamycin production.

PMID- 18633289
TI  - Modulation of the regioselectivity of a Thermotoga neapolitana beta-glucosidase
      by site-directed mutagenesis.
AB  - Thermotoga neapolitana beta-glucosidase (BglA) was subjected to site-directed
      mutagenesis in an effort to increase its ability to synthesize arbutin
      derivatives by transglycosylation. The transglycosylation reaction of the wild
      type enzyme displays major beta(1,6) and minor beta(1,3) or beta(1,4)
      regioselectivity. The three mutants, N291T, F412S, and N291T/F412S, increased the
      ratio of transglycosylation/hydrolysis compared with the wild-type enzyme when
      pNPG and arbutin were used as a substrate and an acceptor, respectively. N291T
      and N219T/F412s had transglycosylation/hydrolysis ratios about 3- and 8-fold
      higher, respectively, than that of the wild-type enzyme. This is due to the
      decreased hydrolytic activity of the mutant rather than increased
      transglycosylation activity. Interestingly, N291T showed altered
      regioselectivity, as well as increased transglycosylation products. TLC analysis
      of the transglycosylation products indicated that N291T retained its beta(1,3)
      regioselectivity, but lost its beta(1,4) and beta(1,6) regioselectivity. The
      altered regioselectivity of N291T using two other acceptors, esculin and salicin,
      was also confirmed by TLC. The major transglycosylation products of the wild type
      and N291T mutant were clearly different. This result suggests that Asn-291 is
      highly involved in the catalytic mechanism by controlling the transglycosylation
      reaction.

PMID- 18633290
TI  - Succinic acid production from continuous fermentation process using Mannheimia
      succiniciproducens LPK7.
AB  - To achieve a higher succinic acid productivity and evaluate the industrial
      applicability, this study used Mannheimia succiniciproducens LPK7 (knock-out:
      lahA, pflB, pta-ackA), which was recently designed to enhance the productivity of
      succinic acid and reduce by-product secretion. Anaerobic continuous fermentation
      of Mannheimia succiniciproducens LPK7 was carried out at different glucose feed
      concentrations and dilution rates. After extensive fermentation experiments, a
      succinic acid yield and productivity of 0.38 mol/mol and 1.77 g/l/h,
      respectively, were achieved with a glucose feed concentration of 18.0 g/l and 0.2
      h-1 dilution rate. A similar amount of succinic acid production was also produced
      in batch culture experiments. Therefore, these optimal conditions can be
      industrially applied for the continuous production of succinic acid. To examine
      the quantitative balance of the metabolism, a flux distribution analysis was also
      performed using the metabolic network model of glycolysis and the pentose
      phosphate pathway.

PMID- 18633291
TI  - Spore inoculum optimization to maximize cyclosporin A production in Tolypocladium
      niveum.
AB  - The cyclic undecapeptide, cyclosporin A (CyA), is one of the most commonly
      prescribed immunosuppressive drugs. It is generated nonribosomally from a
      multifunctional cyclosporin synthetase enzyme complex by the filamentous fungus
      Tolypocladium niveum. In order to maximize the production of CyA by wild-type T.
      niveum (ATCC 34921), each of three culture stages (sporulation culture, growth
      culture, and production culture) were sequentially optimized. Among the three
      potential sporulation media, the SSMA medium generated the highest numbers of T.
      niveum spores. The SSM and SM media were then selected as the optimal growth and
      production culture media, respectively. The addition of valine and fructose to
      the SM production medium was also determined to be crucial for CyA biosynthesis.
      In this optimized three-stage culture system, 3% of the spore inoculum generated
      the highest level of CyA productivity in a 15-day T. niveum production culture,
      thereby implying that the determination of an appropriate size of T. niveum spore
      inoculum plays a critical role in the maximization of CyA production.

PMID- 18633292
TI  - High cell density culture of Anabaena variabilis with controlled light intensity
      and nutrient supply.
AB  - Controlling the light energy and major nutrients is important for high cell
      density culture of cyanobacterial cells. The growth phase of Anabaena variabilis
      can be divided into an exponential growth phase and a deceleration phase. In this
      study, the cell growth in the deceleration phase showed a linear growth pattern.
      Both the period of the exponential growth phase and the average cell growth rate
      in the deceleration phase increased by controlling the light intensity. To
      control the light intensity, the specific irradiation rate was maintained above
      10 micromol/s/g dry cell by increasing the incident light intensity stepwise. The
      final cell density increased by controlling the nutrient supply. For the control
      of the nutrient supply, nitrate, phosphate, and sulfate were intermittently added
      based on the growth yield, along with the combined control of light intensity and
      nutrient concentration. Under these control conditions, both final cell
      concentration and cell productivity increased, to 8.2 g/l and 1.9 g/l/day,
      respectively.

PMID- 18633293
TI  - Improved coexpression and multiassembly properties of recombinant human ferritins
      subunit in Escherichia coli.
AB  - Human heavy chain (H-) and light chain (L-) ferritins were amplified from a human
      cDNA library. Each ferritin gene was inserted downstream of the T7 promoter of
      bacterial expression vectors, and two types of coexpression vectors were
      constructed. The expression levels of recombinant ferritins ranged about 26-36%
      of whole-cell protein. Hferritin exhibited a lower expression ratio compared with
      L-ferritin, by a coexpression system. However, the coexpression of HL-ferritins
      was significantly increased above the expression ratio of H-ferritin by
      cultivation without IPTG induction overnight. Purified recombinant H-, L-, HL-,
      and LHferritins were shown to be homo- and heteropolymeric high molecular
      complexes and it was indicated that their assembled subunits would be able to
      work functionally in the cell. Thus, these results indicate an improvement in the
      expression strategy of H-ferritin for heteropolymeric production and studies of
      ferritin assembly in Escherichia coli.

PMID- 18633294
TI  - Purification and characterization of an extracellular beta-glucosidase from
      Monascus purpureus.
AB  - An extracellular beta-glucosidase produced by Monascus purpureus NRRL1992 in
      submerged cultivation was purified by acetone precipitation, gel filtration, and
      hydrophobic interaction chromatography, resulting in a purification factor of 92
      fold. A 22 central-composite design (CCD) was performed to find the best
      temperature and pH conditions for enzyme activity. Maximum activity was observed
      in a wide range of temperature and pH values, with optimal conditions set at 50
      degrees and pH 5.5. The beta-glucosidase showed moderate thermostability, was
      inhibited by HgCl2, K2CrO4, and K2Cr2O7, whereas other reagents including beta-
      mercaptoethanol, SDS, and EDTA showed no effect. Activity was slightly stimulated
      by low concentrations of ethanol and methanol. Hydrolysis of p-nitrophenyl-beta-D
      glucopyranoside (pNPG), cellobiose, salicin, n-octyl-beta-D-glucopyranoside, and
      maltose indicates that the beta-glucosidase has broad substrate specificity.
      Apparently, glucosyl residues were removed from the nonreducing end of p
      nitrophenyl-beta-Dcellobiose. beta-Glucosidase affinity and hydrolytic efficiency
      were higher for pNPG, followed by maltose and cellobiose. Glucose and cellobiose
      competitively inhibited pNPG hydrolysis.

PMID- 18633295
TI  - Safety assessment of commercial Enterococcus probiotics in Korea.
AB  - There have been concerns about possible pathogenicity and antimicrobial
      resistance in Enterococcus, which constitute more than 50% of probiotics in the
      worldwide market. In this study, Enterococcus in sixteen products manufactured by
      ten different companies was tested for the presence of six virulence genes and
      two vancomycin resistance genes. Results in this study showed the safety of
      Enterococcus on the Korean market and the importance of screening vanA, vanB,
      agg, cylA, esp, and gelE. Pulse-field gel electrophoresis showed that the sixteen
      isolates tested in this study are originated from three strains.

PMID- 18633297
TI  - Isolation and characterization of comprehensive polychlorinated biphenyl
      degrading bacterium, Enterobacter sp. LY402.
AB  - A Gram-negative bacterium, named LY402, was isolated from contaminated soil. 16S
      rDNA sequencing and measurement of the physiological and biochemical
      characteristics identified it as belonging to the genus Enterobacter. Degradation
      experiments showed that LY402 had the ability to aerobically transform 79 of the
      91 major congeners of Aroclor 1242, 1254, and 1260. However, more interestingly,
      the strain readily degraded certain highly chlorinated and recalcitrant
      polychlorinated biphenyls (PCBs). Almost all the tri- and tetra-chlorobiphenyls
      (CBs), except for 3,4,3',4'-CB, were degraded in 3 days, whereas 73% of 3,4,3',4'
      , 92% of the penta-, 76% of the hexa-, and 37% of the hepta-CBs were transformed
      after 6 days. In addition, among 12 octa-CBs, 2,2',3,3',5,5',6,6- CB was
      obviously degraded, and 2,2',3,3',4,5,6,6'- and 2,2',3,3',4,5,5',6'-CB were
      slightly transformed. In a metabolite analysis, mono- and di-chlorobenzoic acids
      (CBAs) were identified, and parts of them were also transformed by strain LY402.
      Analysis of PCB degradation indicated that strain LY402 could effectively degrade
      PCB congeners with chlorine substitutions in both ortho- and para-positions.
      Consequently, this is the first report of an Enterobacteria that can efficiently
      degrade both low and highly chlorinated PCBs under aerobic conditions.

PMID- 18633296
TI  - Biodegradation of organophosphate pesticide using recombinant Cyanobacteria with
      surface- and intracellular-expressed organophosphorus hydrolase.
AB  - The opd gene, encoding organophosphorus hydrolase (OPH) from Flavobacterium sp.
      capable of degrading a wide range of organophosphate pesticides, was surface- and
      intracellular-expressed in Synechococcus PCC7942, a prime example of
      photoautotrophic cyanobacteria. OPH was displayed on the cyanobacterial cell
      surface using the truncated ice nucleation protein as an anchoring motif. A minor
      fraction of OPH was displayed onto the outermost surface of cyanobacterial cells,
      as verified by immunostaining visualized under confocal laser scanning microscopy
      and OPH activity analysis; however, a substantial fraction of OPH was buried in
      the cell wall, as demonstrated by proteinase K and lysozyme treatments. The
      cyanobacterial outer membrane acts as a substrate (paraoxon) diffusion barrier
      affecting whole-cell biodegradation efficiency. After freeze-thaw treatment,
      permeabilized whole cells with intracellular-expressed OPH exhibited 14-fold
      higher bioconversion efficiency (Vmax/Km) than that of cells with surface
      expressed OPH. As cyanobacteria have simple growth requirements and are
      inexpensive to maintain, expression of OPH in cyanobacteria may lead to the
      development of a lowcost and low-maintenance biocatalyst that is useful for
      detoxification of organophosphate pesticides.

PMID- 18633298
TI  - Effectiveness of rhizobacteria containing ACC deaminase for growth promotion of
      peas (Pisum sativum) under drought conditions.
AB  - A series of experiments were conducted to assess the effectiveness of
      rhizobacteria containing 1-aminocyclopropane- 1-carboxylate (ACC) deaminase for
      growth promotion of peas under drought conditions. Ten rhizobacteria isolated
      from the rhizosphere of different crops (peas, wheat, and maize) were screened
      for their growth promoting ability in peas under axenic condition. Three
      rhizobacterial isolates, Pseudomonas fluorescens biotype G (ACC-5), P.
      fluorescens (ACC-14), and P. putida biotype A (Q-7), were selected for pot trial
      on the basis of their source, ACC deaminase activity, root colonization, and
      growth promoting activity under axenic conditions. Inoculated and uninoculated
      (control) seeds of pea cultivar 2000 were sown in pots (4 seeds/pot) at different
      soil moisture levels (25, 50, 75, and 100% of field capacity). Results revealed
      that decreasing the soil moisture levels from 100 to 25% of field capacity
      significantly decreased the growth of peas. However, inoculation of peas with
      rhizobacteria containing ACC deaminase significantly decreased the "drought
      stress imposed effects" on growth of peas, although with variable efficacy at
      different moisture levels. At the lowest soil moisture level (25% field
      capacity), rhizobacterial isolate Pseudomonas fluorescens biotype G (ACC-5) was
      found to be more promising compared with the other isolates, as it caused maximum
      increases in fresh weight, dry weight, root length, shoot length, number of
      leaves per plant, and water use efficiency on fresh and dry weight basis (45,
      150, 92, 45, 140, 46, and 147%, respectively) compared with respective
      uninoculated controls. It is highly likely that rhizobacteria containing ACC
      deaminase might have decreased the drought-stress induced ethylene in inoculated
      plants, which resulted in better growth of plants even at low moisture levels.
      Therefore, inoculation with rhizobacteria containing ACC deaminase could be
      helpful in eliminating the inhibitory effects of drought stress on the growth of
      peas.

PMID- 18633299
TI  - Vaccination of shrimp (Penaeus chinensis) against white spot syndrome virus
      (WSSV).
AB  - Two structural protein genes, VP19 and VP466, of white spot syndrome virus (WSSV)
      were cloned and expressed in Sf21 insect cells using a baculovirus expression
      system for the development of injection and oral feeding vaccines against WSSV
      for shrimps. The cumulative mortalities of the shrimps vaccinated by the
      injection of rVP19 and rVP466 at 15 days after the challenge with WSSV were 50.2%
      and 51.8%, respectively. For the vaccination by oral feeding of rVP19 and rVP466,
      the cumulative mortalities were 49.2% and 89.2%, respectively. These results show
      that protection against WSSV can be generated in the shrimp, using the viral
      structural protein as a protein vaccine.

PMID- 18633300
TI  - Proteomic identification and characterization of Vibrio vulnificus proteins
      induced upon exposure to INT-407 intestinal epithelial cells.
AB  - Proteomic analysis led to identification of the proteins of Vibrio vulnificus
      that were induced upon exposure to INT-407 cells, and 7 of which belong to the
      functional categories such as amino acid transport/metabolism, nucleotide
      transport/metabolism, posttranslational modification/protein turnover/chaperones,
      and translation. Among the genes encoding the host-induced proteins, disruption
      of purH, trpD, tsaA, and groEL2 resulted in reduced cytotoxicity. The purH, trpD,
      and tsaA mutants showed impaired growth in the INT-407 lysate; however, the
      growth rate of the groEL2 mutant was not significantly changed, indicating that
      the possible roles of the host-induced proteins in the virulence of V. vulnificus
      are rather versatile.

PMID- 18633301
TI  - Enhancement of in vivo bone regeneration efficacy of human mesenchymal stem
      cells.
AB  - We investigated whether transplantation of osteogenically differentiated bone
      marrow-derived mesenchymal stem cells (BMMSCs) and the use of an hydroxyapatite
      (HAp) scaffold can enhance the in vivo bone formation efficacy of human BMMSCs.
      Three months after implantation to the subcutaneous dorsum of athymic mice,
      transplantation of osteogenically differentiated human BMMSCs increased the bone
      formation area and calcium deposition to 7.1- and 6.2-folds, respectively, of
      those of transplantation of undifferentiated BMMSCs. The use of the HAp scaffold
      increased the bone formation area and calcium deposition to 3.7- and 3.5-folds,
      respectively, of those of a polymer scaffold. Moreover, a combination of
      transplantation of osteogenically differentiated BMMSCs and HAp scaffold further
      increased the bone formation area and calcium deposition to 10.6- and 9.3-folds,
      respectively, of those of transplantation of undifferentiated BMMSCs seeded onto
      polymer scaffolds. The factorial experimental analysis showed that osteogenic
      differentiation of BMMSCs prior to transplantation has a stronger positive effect
      than the HAp scaffold on in vivo bone formation.

PMID- 18633302
TI  - Effects of beta-mercaptoethanol and hydrogen peroxide on enzymatic conversion of
      human proinsulin to insulin.
AB  - Human insulin is a hormone well-known to regulate the blood glucose level.
      Recombinant preproinsulin, a precursor of authentic insulin, is typically
      produced in E. coli as an inactive inclusion body, the solubilization of which
      needs the addition of reducing agents such as beta-mercaptoethanol. To make
      authentic insulin, recombinant preproinsulin is modified enzymatically by trypsin
      and carboxypeptidase B. The effects of beta-mercaptoethanol on the formation of
      human insulin derivatives were investigated in the enzymatic modification by
      using commercially available human proinsulin as a substrate. Addition of 1 mM
      beta-mercaptoethanol induced the formation of various insulin derivatives. Among
      them, the second major one, impurity 3, was found to be identical to the insulin
      B chain fragment from Phe1 to Glu21. Minimization of the formation of insulin
      derivatives and concomitant improvement of the production yield of human insulin
      were achieved by the addition of hydrogen peroxide. Hydrogen peroxide bound with
      beta-mercaptoethanol and thereby reduced the negative effects of beta
      mercaptoethanol considerably. Elimination of the impurity 3 and other derivatives
      by the addition of over 10 mM hydrogen peroxide in the presence of beta
      mercaptoethanol led to a 1.3-fold increase in the recovery efficiency of insulin,
      compared with those for the case without hydrogen peroxide. The positive effects
      of hydrogen peroxide were also confirmed with recombinant human preproinsulin
      expressed in recombinant E. coli as an inclusion body.

PMID- 18633303
TI  - Effective antibacterial action of tat (47-58) by increased uptake into bacterial
      cells in the presence of trypsin.
AB  - In a previous study, we found an antifungal effect on human pathogenic fungi by
      the cell-penetrating peptide Tat (47-58) derived from HIV-1. Tat (47-58)
      immediately entered into the fungal nucleus and affected some physiological
      changes on the intracellular condition. In this study, Tat (47-58) showed a broad
      spectrum of antibacterial activity against pathogenic bacteria including
      bacterial clinical isolates. To improve resistance against proteases for use in
      vivo, we synthesized an analog of Tat (47-58) by substituting the L-amino acid
      for the D-amino acid. The D-enantiomer of Tat (47-58) also exhibited a broad
      spectrum of antibacterial activity at almost the same level of L-Tat (47-58)
      concentration. Unlike L-Tat (47-58), D-Tat (47-58) showed a significant
      proteolytic resistance against all proteases tested and antimicrobial activities
      in the presence of trypsin. Moreover, D-Tat (47-58) inhibited MRSA infection in
      human HeLa cells whereas L-Tat (47-58) partially allowed MRSA infection, and the
      results were due to the proteolytic resistance of D-Tat (47-58).

PMID- 18633304
TI  - Dry-heat treatment process for enhancing viral safety of an antihemophilic factor
      VIII concentrate prepared from human plasma.
AB  - Viral safety is a prerequisite for manufacturing clinical antihemophilic factor
      VIII concentrates from human plasma. With particular regard to the hepatitis A
      virus (HAV), a terminal dry-heat treatment (100 degrees for 30 min) process,
      following lyophilization, was developed to improve the virus safety of a
      solvent/detergent-treated antihemophilic factor VIII concentrate. The loss of
      factor VIII activity during dry-heat treatment was of about 5%. No substantial
      changes were observed in the physical and biochemical characteristics of the dry
      heat-treated factor VIII compared with those of the factor VIII before dry-heat
      treatment. The dry-heat-treated factor VIII was stable for up to 24 months at
      4oC. The dry-heat treatment after lyophilization was an effective process for
      inactivating viruses. The HAV, murine encephalomyocarditis virus (EMCV), and
      human immunodeficiency virus (HIV) were completely inactivated to below
      detectable levels within 10 min of the dry-heat treatment. Bovine herpes virus
      (BHV) and bovine viral diarrhea virus (BVDV) were potentially sensitive to the
      treatment. However porcine parvovirus (PPV) was slightly resistant to the
      treatment. The log reduction factors achieved during lyophilization and dry-heat
      treatment were > or =5.55 for HAV, > or =5.87 for EMCV, > or =5.15 for HIV, 6.13
      for BHV, 4.46 for BVDV, and 1.90 for PPV. These results indicate that dry-heat
      treatment improves the virus safety of factor VIII concentrates, without
      destroying the activity. Moreover, the treatment represents an effective measure
      for the inactivation of non-lipid-enveloped viruses, in particular HAV, which is
      resistant to solvent/detergent treatment.

PMID- 18633305
TI  - Chronic constipation causing obstructive uropathy in an adolescent male.
AB  - Chronic constipation causing obstructive uropathy is very rare in children and
      young adults. Nevertheless, it is one of the possible complications of ongoing
      constipation and can cause severe renal function impairment with the need for
      emergent disimpaction. We review the case of a young adult who presented to our
      emergency department with acute renal failure due to fecal impaction.

PMID- 18633306
TI  - Bilateral radial neck fractures in a child: report of a case.
AB  - Fractures of the proximal radius are among the most common fractures and account
      for 9% to 25% of the elbow fractures in children. However, bilateral radial neck
      fractures are extremely rare injuries in children and have been reported only
      once before in present English literature. We report a case of bilateral radial
      neck fractures in a 10-year-old girl resulting from a fall on outstretched hands.
      Careful physical examination and proper radiographs are necessary for the
      diagnosis. Early recognition, proper management, and physical therapy led to
      complete recovery and full functional movement of the elbows.

PMID- 18633307
TI  - Foot injuries associated with all-terrain vehicle use in children and
      adolescents.
AB  - OBJECTIVES: Children can suffer serious foot injuries while riding or driving an
      all-terrain vehicle (ATV). The purpose of this study was to describe this injury
      pattern. METHODS: A search of the trauma registry of the Arkansas Children's
      Hospital for the years 1998 through 2006 was conducted to find cases of children
      admitted for treatment of foot injuries related to ATV use. The cases were
      deidentified and summarized. The study was reviewed and deemed to be exempt by
      the local institutional review board. RESULTS: Ten cases of foot injury were
      identified. The median age was 3 years. Eight had forefoot injuries, including 6
      who had amputation of the great toe. All but one patient had multiple open foot
      fractures. Seven required skin grafting. Complications included infection, scar
      formation, disfigurement, and gait disturbance. The mean length of stay on
      initial hospitalization was 6 days, and the mean hospital charge was $12,890.
      CONCLUSIONS: Children, particularly young children, on an ATV can suffer serious
      foot injuries resulting in disfigurement and disability. The recommendation that
      young children not ride on ATVs is emphasized by these findings.

PMID- 18633308
TI  - Corneal injury due to a calcium hydroxide containing food preparation product
      ("cal").
AB  - Alkaline chemicals can cause severe ocular injury, leaving the victim with
      significant visual impairment. Calcium hydroxide is a strong alkali present in
      some household products. We report a case of corneal alkali burns in a 5-year-old
      boy due to calcium hydroxide powder ("cal") used in preparation of corn masa.
      Prompt recognition of "cal" as calcium hydroxide will allow the practitioner to
      appropriately render effective treatment.

PMID- 18633309
TI  - Congenital transmesosigmoid hernia: a rare case of pediatric small-bowel
      obstruction.
AB  - A transmesocolic hernia is an uncommon type of internal hernia. We present a case
      of an internal hernia, through a congenital defect of the sigmoid mesocolon in a
      3-year-old girl referred to our hospital with acute pain in the left abdominal
      region and vomiting. Because of the progressive worsening of her clinical status,
      an early laparotomy was performed and the intraoperative findings were consistent
      with a transmesosigmoid hernia. The hernia's sac contained gangrenous ileum
      loops, which were resected, and the defect was closed. Postoperative outcome was
      uneventful and the patient was discharged on the 10th postoperative day.

PMID- 18633310
TI  - Multiple seizures after bupropion overdose in a small child.
AB  - Unintentional ingestion of bupropion in young children has generally resulted in
      limited toxicity. We report a case of pediatric bupropion ingestion resulting in
      multiple seizures. The patient experienced hallucinations, agitation, vomiting,
      tachycardia and seizures after ingestion of 1050 (48 mg/kg) of extended-release
      bupropion. The potential for severe toxicity in the setting of pediatric overdose
      should be recognized.

PMID- 18633311
TI  - Fell while playing: cousin fell on arm, a little pain.

PMID- 18633312
TI  - Pediatric disaster preparedness: best planning for the worst-case scenario.
AB  - Natural and man-made disasters are unpredictable but certainly will include
      children as victims. Increasingly, knowledge of pediatric disaster preparedness
      is required of emergency and primary care practitioners. A complete pediatric
      disaster plan comprises the following elements: appropriate personnel and
      equipment, disaster- and venue-specific training, and family preparedness.
      Disaster preparedness exercises are crucial for training plan implementation and
      response evaluation. Exercise content depends on local hazard vulnerabilities and
      learner training needs. Postexercise evaluations follow a stepwise process that
      culminates in improved disaster plans. This article will review disaster planning
      and the design, implementation, and evaluation of pediatric disaster exercises.

PMID- 18633314
TI  - Children's mental health emergencies--part 2: emergency department evaluation and
      treatment of children with mental health disorders.
AB  - OBJECTIVE: The emergency physician should be familiar with the wide spectrum of
      pediatric mental health emergencies because they are commonly encountered in
      emergency medical practice. METHODS: A review of the literature was done in order
      to develop an approach for dealing with children presenting with mental health
      disorders in the emergency department (ED). RESULTS: Children' mental health
      emergencies have a wide spectrum from behavioral disturbances to major
      depression. An approach to the issues involved in caring for these patients is
      discussed which acknowledges the essential role of the emergency physician and
      the importance of integrating ED care with multidisciplinary services.
      CONCLUSIONS: The actions and directions taken in the ED are a crucial part of the
      child's long-term care and treatment. The ED evaluation and management of
      pediatric mental health emergencies may vary depending on the complaint and
      includes differentiation from organic etiologies, medical stabilization, and
      occasionally in depth psychosocial interview.

PMID- 18633315
TI  - ECGs in the ED.

PMID- 18633316
TI  - The 2006-2007 PEMpix photo competition award winner: Mark Cicero, MD: Rash
      decisions: acute hemorrhagic edema of infancy in a 7-month-old boy.

PMID- 18633318
TI  - The 2007-2008 photo competition award winner: Melissa Langhan, MD: A painful
      scalp rash: cutaneous myiasis secondary to new world screwworm.

PMID- 18633319
TI  - Collagen XVII/BP180 protein expression in squamous cell carcinoma of the skin
      detected with novel monoclonal antibodies in archived tissues using tissue
      microarrays and digital microscopy.
AB  - Collagen XVII/BP180, a hemidesmosomal adhesion protein, is lost during normal
      keratinocyte maturation; however, it may be reexpressed upon malignant
      transformation. In this work, highly sensitive monoclonal antibodies 6D1 and 9G2
      were produced, characterized, and used for the detection of collagen XVII in a
      tissue microarray series of archived samples of nonmelanocytic epithelial
      neoplasias, including 5 verruca vulgaris, 14 seborrheic keratosis, 38 actinic
      keratosis, 38 basal cell carcinoma (BCC), 15 basosquamous carcinoma, 58 squamous
      cell carcinoma (SCC), and 9 normal skin. Digital microscopy and a new tissue
      microarray software linking image and patient data allowed easy and validated
      evaluation and quality archiving of stained samples. In normal skin and benign
      epidermal lesions, collagen XVII protein was restricted to basal keratinocytes.
      However, possibly as a sign of undifferentiated/transformed state, it was widely
      expressed in SCC showing elevated levels around invasive tumor fronts with some
      staining in tumor adjacent stroma, endothelium, and histiocytes. Collagen XVII
      immunostaining of atypical keratinocytes in most actinic/solar keratosis supports
      the view of their malignancy and common origin with SCC. Squamous component of
      basosquamous carcinoma showed moderate reaction, whereas islets of BCC were
      mainly negative reflecting the diverse genotype and phenotype, and pathogenesis
      of SCC and BCC. These results suggest that collagen XVII neoexpression may be
      associated with early atypia/malignant transformation of keratinocytes. Further
      investigations are under way to analyze the potential of these antibodies for
      tracing progression and metastatic potential of skin tumors.

PMID- 18633320
TI  - High concordance of SP3 rabbit monoclonal antibody with FISH to evaluate HER2 in
      breast carcinoma.
AB  - HER2 gene amplification or HER2 protein overexpression predicts a more aggressive
      clinical course in breast cancer, with a worse response to hormonal therapy, and
      determines eligibility for the use of the anti-HER2 antibody trastuzumab. For
      these reasons, the diagnostic assays that determine HER2 status in breast
      carcinoma have become increasingly important. Our goal was to evaluate the
      concordance, sensitivity, and specificity of a rabbit monoclonal antibody
      directed to the extracellular domain of the HER2 receptor (SP3) and compare it
      with fluorescence in situ hybridization and HercepTest in 179 invasive breast
      carcinomas. We found that SP3 was in agreement with fluorescence in situ
      hybridization results in 94.6% of cases. HercepTest and fluorescence in situ
      hybridization results were in agreement in 95.1% of the cases. Only 4.3% (4/93)
      of the cases that scored 0/1+ by SP3 were amplified by fluorescence in situ
      hybridization, and 8.3% (3/36) of cases that scored 3+ were not amplified by
      fluorescence in situ hybridization. Comparing SP3 with HercepTest, we observed
      that HercepTest demonstrated higher sensitivity (100.0% vs. 89.0%) but SP3
      demonstrated higher specificity (97.0% vs. 89.0%). An important advantage of SP3
      (in comparison with HercepTest) is its higher discrimination power (72.1% vs.
      34.1%). For these reasons, this antibody could be helpful in the determination of
      HER2 status in a routine basis.

PMID- 18633321
TI  - Immunohistochemical expression of SNAP-25 protein in adenomas of the human
      pituitary.
AB  - SNAP-25, a synaptosome-associated exocytosis protein of 25 kd mw, plays an
      important role in the secretory activity of several endocrine cells. In the
      present study, we investigated surgically removed pituitary adenomas including 40
      prolactin (PRL), 31 growth hormone, 5 adrenocorticotropic hormone, 5 thyroid
      stimulating hormone, 14 follicle-stimulating hormone/luteinizing hormone/alpha
      subunit-producing tumors, and 5 null cell adenomas. Among the 40 patients with
      PRL-producing pituitary adenoma, 16 had been preoperatively treated with the
      dopamine agonist bromocriptine. Similarly, of the 31 patients with GH-producing
      pituitary adenomas, 15 had been treated with the long-acting somatostatin analog,
      octreotide. All tumors were subjected to transsphenoidal surgery, formalin-fixed,
      routinely processed, and paraffin-embedded. Sections of 4 to 6-microm thickness
      were stained with hematoxylin and eosin and the periodic acid-Schiff as well as
      the Gordon-Sweet silver methods. Immunostaining for SNAP-25 (streptavidin-biotin
      peroxidase complex method) showed that 10 PRL-producing adenomas were strongly
      immunoreactive. Immunopositivity was mainly cell membrane in distribution but
      several cells showed mild cytoplasmic staining. Nuclei were immunonegative.
      Preoperative bromocriptine treatment markedly decreased SNAP-25 immunopositivity.
      Among GH-producing adenomas, SNAP-25 was seen in 5 cases; reactivity being mild
      to-moderate, membrane-bound, and cytoplasmic. Octreotide caused no significant
      reduction in immunopositivity. Other adenoma types were virtually immunonegative.
      Six autopsy-derived human pituitaries and 4 surgically obtained nontumorous
      pituitaries were also immunonegative for SNAP-25. It is conceivable that SNAP-25
      plays an important role in PRL release and is involved in the bromocriptine
      induced suppression of PRL secretion from PRL-producing adenoma cells.

PMID- 18633322
TI  - Immunohistochemistry on frozen section of sentinel lymph nodes in breast cancer
      with improved morphology and blocking of endogenous peroxidase.
AB  - Sentinel lymph node biopsy in the management of patients with breast cancer is
      the clinical practice. Peroperative examination means that more patients can be
      treated in a 1-step procedure. The addition of immunohistochemistry to frozen
      section slides improves the detection rate of especially micrometastasis. We
      present a novel method for immunohistochemical staining on a frozen section
      material that gives better morphology and blocks endogenous peroxidase
      sufficiently.

PMID- 18633323
TI  - Young adults' use and output level settings of personal music systems.
AB  - OBJECTIVES: There are growing concerns over noise exposure via personal music
      system use by young adults. One purpose of this study was to evaluate the
      prevalence of personal music system use and the listening patterns associated
      with these systems in a large sample of young adults. A second purpose of this
      study was to measure the dB SPL in the ear canal of young adults while they
      blindly set the volume of a personal music system to four settings. DESIGN: In
      the first study, the personal music system use survey was completed by 1016
      students at various locations on the San Diego State University campus. Questions
      included sex, age, ethnicity, race, and whether or not they used a personal music
      system. Students who answered Yes to using a personal music system were
      instructed to complete the remaining 11 closed-set questions. These questions
      dealt with type of earphones used with the system, most common listening
      environment, length of time per day the system was used, and the volume setting.
      The differences between women and men and across ethnicity and race were
      evaluated for the questions. In the second study, a probe microphone placed in
      the ear canal of 32 participants was used to determine the dB SPL of four
      loudness categories at which the participants blindly set the level of a personal
      music system: low, medium or comfortable, loud, and very loud. RESULTS: In study
      1, over 90% of the participants who completed the survey reported using a
      personal music system. Over 50% of those who use a personal music system reported
      listening between 1 and 3 hrs and almost 90% reported listening at either a
      medium or loud volume. Men were significantly more likely to report listening to
      their system for a longer duration compared with women and more likely to report
      listening at a very loud volume. There was a trend for Hispanic or Latino
      students to report listening for longer durations compared with Not Hispanic or
      Latino students, but this difference was not statistically significant. Black or
      African American students were significantly more likely to report listening to
      their personal music system between 3 and 5 hrs and more than 5 hrs and to report
      listening at a very loud volume compared with other racial groups. In study 2,
      the mean dB SPL values for low, medium or comfortable, loud, and very loud were
      62.0, 71.6, 87.7, and 97.8 dB SPL, respectively. Men set the level of very loud
      significantly higher than women. CONCLUSIONS: It is clear that a vast majority of
      young adults who completed the personal music system use survey listen to a
      system using earphones. Most of the respondents listen between 1 and 3 hrs a day
      at a medium or loud volume. Based on the probe microphone measurement results,
      the volume settings for reported durations may not be hazardous for hearing. Long
      term use of personal music systems, however, in combination with other noise
      exposures (i.e., recreational, occupational), and their effect on hearing remains
      a question for additional research.

PMID- 18633324
TI  - Electrophysiological spread of excitation and pitch perception for dual and
      single electrodes using the Nucleus Freedom cochlear implant.
AB  - OBJECTIVES: The first objective of the study was to determine whether there were
      any consistent differences in the electrophysiological spread of excitation (SOE)
      function, as measured using the electrically evoked compound action potential
      (ECAP), between dual and single electrode stimulation with the Nucleus Freedom
      cochlear implant system. Dual electrode stimulation is produced by electrically
      coupling two adjacent single electrodes. The second objective was to determine
      whether there were any relationships between the SOE functions and
      psychophysically measured pitch ranking of dual and single electrodes. DESIGN:
      Nine adult cochlear implant subjects participated in the study. ECAPs for dual
      and single electrode stimulation were measured using the forward masking
      paradigm, as also used in the Neural Response Telemetry (NRT) software with the
      Nucleus implant. Research software was used to generate the dual and single
      electrode stimuli and record the ECAPs. Spread of excitations (SOEs) were
      measured on a dual electrode and the two adjacent single electrodes, at three
      positions on the array: apical, mid, and basal. Compared were the ECAP amplitudes
      at the peak of the SOE functions, the widths of the scaled SOE functions at the
      75% point, and the electrode positions at the peak of the SOE function and at the
      75%, 50%, and 25% points on apical and basal sides of the scaled functions. Pitch
      ranking was measured for the same sets of dual and single electrodes. A two
      alternative forced choice procedure was used, with the electrodes in each set
      paired with each other as AB and BA pairs. The subject indicated which of the two
      stimuli had the higher pitch. RESULTS: Dual electrode SOEs could be successfully
      obtained using the same methods as used to measure single electrode SOEs. The
      shapes of the dual and single electrodes SOEs were similar. There was a trend of
      a higher ECAP amplitude for the dual electrode at the peak of the SOE function,
      but this was only significant for two comparisons at the apical and basal
      positions. There were no significant differences in the SOE widths between dual
      and single electrodes. The electrodes at the peak of the SOE function and on the
      apical and basal sides of the function at the 75% position were, in most cases,
      tonotopically ordered. At the 50% and 25% positions, there were fewer significant
      differences between the dual and single electrodes The pitch ranking results
      showed that in 74% of cases, the single and dual electrodes at each position were
      successfully ranked in the expected tonotopic order. There were no statistically
      significant correlations between the pitch ranking results and the ordering of
      electrodes on the SOE functions. CONCLUSIONS: Dual electrode stimulation produced
      similar SOE functions as single electrode stimulation. A tonotopic ordering of
      electrodes at the peak of the SOE and on the sides of the functions was found,
      but this was not statistically related to the pitch ranking results. SUMMARY:
      Electrophysiological spread of neural excitation (SOE) and pitch perception using
      dual and single electrodes was investigated in nine subjects using the Nucleus
      Freedom cochlear implant. Dual electrodes are produced by electrically coupling
      two adjacent single electrodes. The dual and single electrodes SOEs were similar
      in shape. Higher electrophysiological response amplitudes were generally found
      for the dual electrodes. There were no differences in SOE widths between dual and
      single electrodes. In three quarters of cases, dual and single electrodes were
      successfully pitch ranked in the expected tonotopic order. No significant
      relationships between pitch ranking and the SOE functions were found.

PMID- 18633325
TI  - The benefit obtained from visually displayed text from an automatic speech
      recognizer during listening to speech presented in noise.
AB  - OBJECTIVES: The aim of this study was to evaluate the benefit that listeners
      obtain from visually presented output from an automatic speech recognition (ASR)
      system during listening to speech in noise. DESIGN: Auditory-alone and
      audiovisual speech reception thresholds (SRTs) were measured. The SRT is defined
      as the speech-to-noise ratio at which 50% of the test sentences are reproduced
      correctly. In the auditory-alone SRT tests, the test sentences were presented
      only auditorily; in the audiovisual SRT test, the ASR output of each test
      sentence was also presented textually. The ASR system was used in two recognition
      modes: recognition of spoken words (word output), or recognition of speech sounds
      or phones (phone output). The benefit obtained from the ASR output was defined as
      the difference between the auditory-alone and the audiovisual SRT. We also
      examined the readability of unimodally displayed ASR output (i.e., the percentage
      of sentences in which ASR errors were identified and accurately corrected). In
      experiment 1, the readability and benefit obtained from ASR word output (n = 14)
      was compared with the benefit obtained from ASR phone output (n = 10). In
      experiment 2, the effect of presenting an indication of the ASR confidence level
      was examined (n = 14). The effect of delaying the presentation of the text
      relative to the speech (up to 6 sec) was examined in experiment 3 (n = 24). The
      ASR accuracy level was varied systematically in each experiment. RESULTS: Mean
      readability scores ranged from 0 to 46%, depending on ASR accuracy. Speech
      comprehension improved when the ASR output was displayed. For example, when the
      ASR output corresponded to readability scores of only about 20% correct, the text
      improved the SRT by about 3 dB SNR in the audiovisual SRT test. This improvement
      corresponds to an increase in speech comprehension of about 35% in critical
      conditions. Equally readable phone and word output provides similar benefit in
      speech comprehension. For equal ASR accuracies, both the readability and the
      benefit from the word output generally exceeded the benefits from the phone
      output. Presenting information about the ASR confidence level did not influence
      either the readability or the benefit obtained from the word output. Delaying the
      text relative to the speech moderately decreased the benefit. CONCLUSIONS: The
      present study indicates that speech comprehension improves considerably by
      textual ASR output with moderate accuracies. The study shows that this
      improvement depends on the readability of the ASR output. Word output has better
      accuracy and readability than phone output. Listeners are therefore better able
      to use the ASR word output than phone output to improve speech comprehension. The
      ability of older listeners and listeners with hearing impairments to use ASR
      output in speech comprehension requires further study.

PMID- 18633326
TI  - Long-term exposure to traffic-related air pollution and lung cancer risk.
AB  - BACKGROUND: Most studies on the association between lung cancer and air pollution
      have investigated mortality. There have been few studies of lung cancer
      incidence. METHODS: We used data from the ongoing Netherlands Cohort Study on
      Diet and Cancer for 114,378 subjects with follow-up from September 1986 to
      December 1997. Exposure to black smoke, nitrogen dioxide (NO2), sulfur dioxide
      (SO2), and particulate matter < or =2.5 microm (PM2.5) and traffic intensity
      variables (intensity on nearest road, intensity in a 100 m buffer, and an
      indicator variable for living close to a major road) were estimated at the home
      address. We conducted Cox proportional hazard analyses in the full cohort
      adjusting for age, sex, smoking status, and area-level socioeconomic status. We
      also carried out case-cohort analyses using more potential confounders on a
      subset of study participants for whom complete information from the baseline
      questionnaire had been processed. RESULTS: Adjusted analyses included 1940 cases
      for the full cohort and 1295 cases for the case-cohort analysis. Relative risks
      (RRs) for the overall air pollution concentrations were slightly below unity, and
      for the traffic variables RRs were slightly elevated. Risk was elevated among
      people who never smoked cigarettes (40,114 participants; 252 cases), with RRs of
      1.47 (95% confidence interval = 1.01-2.16) for overall black smoke concentration,
      1.11 (0.88-1.41) for traffic intensity on nearest road, and 1.55 (0.98-2.43) for
      living near a major road. CONCLUSIONS: We found evidence for an association of
      exposure to black smoke and traffic with lung cancer incidence in people who had
      never smoked. No associations were found for the full cohort, or for other
      categories of smoking.

PMID- 18633327
TI  - Air pollution and mortality in Latin America: the role of education.
AB  - BACKGROUND: People with less education in Europe, Asia, and the United States are
      at higher risk of mortality associated with daily and longer-term air pollution
      exposure. We examined whether educational level modified associations between
      mortality and ambient particulate pollution (PM10) in Latin America, using
      several timescales. METHODS: The study population included people who died during
      1998-2002 in Mexico City, Mexico; Santiago, Chile; and Sao Paulo, Brazil. We fit
      city-specific robust Poisson regressions to daily deaths for nonexternal-cause
      mortality, and then stratified by age, sex, and educational attainment among
      adults older than age 21 years (none, some primary, some secondary, and high
      school degree or more). Predictor variables included a natural spline for
      temporal trend, linear PM10 and apparent temperature at matching lags, and day-of
      week indicators. We evaluated PM10 for lags 0 and 1 day, and fit an unconstrained
      distributed lag model for cumulative 6-day effects. RESULTS: The effects of a 10
      microg/m increment in lag 1 PM10 on all nonexternal-cause adult mortality were
      for Mexico City 0.39% (95% confidence interval = 0.13%-0.65%); Sao Paulo 1.04%
      (0.71%-1.38%); and for Santiago 0.61% (0.40%-0.83%). We found cumulative 6-day
      effects for adult mortality in Santiago (0.86% [0.48%-1.23%]) and Sao Paulo
      (1.38% [0.85%-1.91%]), but no consistent gradients by educational status.
      CONCLUSIONS: PM10 had important short- and intermediate-term effects on mortality
      in these Latin American cities, but associations did not differ consistently by
      educational level.

PMID- 18633328
TI  - Why most discovered true associations are inflated.
AB  - Newly discovered true (non-null) associations often have inflated effects
      compared with the true effect sizes. I discuss here the main reasons for this
      inflation. First, theoretical considerations prove that when true discovery is
      claimed based on crossing a threshold of statistical significance and the
      discovery study is underpowered, the observed effects are expected to be
      inflated. This has been demonstrated in various fields ranging from early stopped
      clinical trials to genome-wide associations. Second, flexible analyses coupled
      with selective reporting may inflate the published discovered effects. The
      vibration ratio (the ratio of the largest vs. smallest effect on the same
      association approached with different analytic choices) can be very large. Third,
      effects may be inflated at the stage of interpretation due to diverse conflicts
      of interest. Discovered effects are not always inflated, and under some
      circumstances may be deflated-for example, in the setting of late discovery of
      associations in sequentially accumulated overpowered evidence, in some types of
      misclassification from measurement error, and in conflicts causing reverse
      biases. Finally, I discuss potential approaches to this problem. These include
      being cautious about newly discovered effect sizes, considering some rational
      down-adjustment, using analytical methods that correct for the anticipated
      inflation, ignoring the magnitude of the effect (if not necessary), conducting
      large studies in the discovery phase, using strict protocols for analyses,
      pursuing complete and transparent reporting of all results, placing emphasis on
      replication, and being fair with interpretation of results.

PMID- 18633329
TI  - Drinking water disinfection by-product exposure and duration of gestation.
AB  - BACKGROUND: Recent studies suggest elevated exposure to drinking water
      disinfection by-products (DBPs) may be associated with decreased risk of preterm
      birth. We examined this association for exposure to total trihalomethanes
      (TTHMs), 5 haloacetic acids (HAA5), and total organic halides. METHODS: Analysis
      included 2039 women in a prospective pregnancy study conducted from 2000 through
      2004 in 3 study sites. Water samples were collected and analyzed for DBP
      concentrations. Participant data were collected through interviews, an early
      ultrasound, and birth records. We assessed the associations between DBPs and
      preterm birth (<37-weeks' gestation) using log-binomial regression. Discrete-time
      hazard analysis was used to model the conditional odds of delivery each week in
      relation to DBP exposure. RESULTS: Average second trimester DBP levels were
      associated with lower risk of preterm birth. Adjusted risk ratios for TTHM levels
      of 33.1-55.0, 55.1-66.3, 66.4-74.8, and 74.9-108.8 microg/L versus 2.2-4.6
      microg/L were 0.8 (95% confidence intervals = 0.5-1.3), 0.9 (0.6-1.4), 0.7 (0.4
      1.1), and 0.5 (0.3-0.9), respectively. Risk ratios for HAA5 levels of 17.9-22.0,
      22.1-31.5, 31.6-40.4, and 40.5-52.8 microg/L versus 0-0.9 microg/L were 1.1 (0.8
      1.7), 0.8 (0.5-1.2), 0.5 (0.3-0.8), and 0.7 (0.4-1.1), respectively. The
      conditional odds of delivery each week were decreased for the highest TTHM and
      HAA5 exposure groups versus the low exposure group for gestational weeks 33-40.
      CONCLUSIONS: The probability of preterm birth was not increased with high DBP
      exposure.

PMID- 18633330
TI  - Drinking water disinfection by-product exposure and fetal growth.
AB  - BACKGROUND: Previous studies suggest that elevated exposure to drinking water
      disinfection by-products (DBPs)--in particular, total trihalomethanes (TTHMs)-
      may lead to fetal growth restriction. We examined the effects of exposure to
      TTHMs, haloacetic acids, and total organic halide on the probability of
      delivering a small-for-gestational-age (SGA) infant and on birth weight at term.
      METHODS: Women early in pregnancy (< or =12 weeks' gestation) or planning a
      pregnancy were enrolled in a prospective pregnancy study conducted in 3 US
      communities from 2000 through 2004. Weekly (or biweekly) water samples were
      collected at each site as well as individual-level participant data. Associations
      between DBP exposures (TTHMs, haloacetic acids, total organic halide) and fetal
      growth were assessed using log-binomial regression for SGA (n = 1958) and linear
      regression for term birth weight (n = 1854). We conducted a Bayesian analysis to
      examine associations between individual DBP species and fetal growth. RESULTS:
      Haloacetic acids and total organic halide were not associated with SGA or term
      birth weight. The probability of delivering an SGA infant was elevated when
      comparing women with an average third-trimester residential TTHM concentration >
      or =80 microg/L to women with exposure <80 microg/L (risk ratio = 2.0 [95%
      confidence interval = 1.1-3.6]), but not when examining other exposure contrasts.
      Bayesian analyses did not support a consistent association between any DBP
      species and fetal growth, although these analyses were based on small sample
      sizes. CONCLUSIONS: Our results do not suggest an adverse effect of haloacetic
      acid or total organic halide exposure on fetal growth. An association of TTHM
      with SGA was seen only for average residential concentrations above the current
      regulatory standard.

PMID- 18633331
TI  - Causal directed acyclic graphs and the direction of unmeasured confounding bias.
AB  - We present results that allow the researcher in certain cases to determine the
      direction of the bias that arises when control for confounding is inadequate. The
      results are given within the context of the directed acyclic graph causal
      framework and are stated in terms of signed edges. Rigorous definitions for
      signed edges are provided. We describe cases in which intuition concerning signed
      edges fails and we characterize the directed acyclic graphs that researchers can
      use to draw conclusions about the sign of the bias of unmeasured confounding. If
      there is only one unmeasured confounding variable on the graph, then
      nonincreasing or nondecreasing average causal effects suffice to draw conclusions
      about the direction of the bias. When there are more than one unmeasured
      confounding variable, nonincreasing and nondecreasing average causal effects can
      be used to draw conclusions only if the various unmeasured confounding variables
      are independent of one another conditional on the measured covariates. When this
      conditional independence property does not hold, stronger notions of monotonicity
      are needed to draw conclusions about the direction of the bias.

PMID- 18633332
TI  - Imbalanced intrahepatic cytokine expression of interferon-gamma, tumor necrosis
      factor-alpha, and interleukin-10 in patients with acute-on-chronic liver failure
      associated with hepatitis B virus infection.
AB  - GOALS: This study attempts to determine expressions of intrahepatic
      proinflammatory and anti-inflammatory cytokines and their secreting immunocytes
      to evaluate their roles in the pathogenesis of acute-on-chronic liver failure
      (ACLF) in chronically hepatitis B virus (HBV)-infected patients. BACKGROUND: ACLF
      generally affects patients with established, compensated chronic liver diseases
      who develop an acute deterioration in liver function. In China, HBV-associated
      ACLF patients account for more than 80% of ACLF patients owing to a high
      prevalence of chronic HBV infection. Clinical observation showed that the
      deterioration of this disease may correlate with host immune responses, but
      related underlying mechanism remains largely unknown. STUDY: In situ expressions
      of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha),
      interleukin-10 (IL-10), and their secreting CD4, CD8 T cells, and Kupffer cells
      (KCs) were analyzed in the livers of patients with ACLF, chronic hepatitis B
      (CHB), and normal controls (NC) using immunohistochemistry. RESULTS: Intrahepatic
      proinflammatory IFN-gamma and TNF-alpha expressions were markedly up-regulated in
      ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10
      expressions were observed in ACLF and CHB. IFN-gamma overexpression correlated
      significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up
      regulation also correlated significantly with increased KCs. CONCLUSIONS: The
      imbalanced expression of proinflammatory and anti-inflammatory cytokines and
      increased accumulation of CD4, CD8 T cells, and KCs may contribute to
      immunopathogenesis in HBV-infected ACLF.

PMID- 18633333
TI  - Prenatal exposure to methamphetamine presenting as neonatal cholestasis.
AB  - INTRODUCTION: Methamphetamine has been recognized as a common cause of acute
      toxic hepatitis in adults with clinical and histologic features indistinguishable
      from acute viral hepatitis. Clinical presentation of methamphetamine
      hepatotoxicity ranges from mild acute hepatitis with prompt recovery to fulminant
      hepatic failure. The pathophysiology of this hepatotoxicity is not well
      elucidated. Prenatal exposure to methamphetamine has been linked to intrauterine
      growth retardation and variety of withdrawal symptoms. Neonatal cholestasis is
      rare but serious problem that indicates hepatobiliary dysfunction and has several
      categories of etiologies. These include infectious, metabolic, endocrine, toxic,
      structural, familial, and autoimmune disorders. Cholestatic hepatitis is a
      recognized complication of exposure to some drugs including carbamazepine and
      trimethoprim-sulfamethoxazole. CASE: A 35-week preterm, appropriate for
      gestational age, white girl was born to a 39-year-old mother who had no prenatal
      care. The mother's urine drug screen revealed methamphetamine. The baby passed
      pale meconium and her subsequent stools were hypo-pigmented. A detailed work up
      was done and was unremarkable except for hepatobiliary scintigraphy, with no
      activity noted in the small bowel on delayed imaging. An operative cholangiogram
      and liver biopsy were performed. The cholangiogram revealed patent bile ducts.
      Liver biopsy was consistent with acute viral or toxic hepatitis. Gradual drop of
      bilirubin was noted. With negative extensive work up for other etiology, known
      hepatotoxicity of methamphetamine, early onset of cholestasis that improved
      without specific therapy, it is strongly suspected that prenatal exposure to
      methamphetamine is the most likely culprit in this patient. DISCUSSION: This is
      the first recorded case of neonatal cholestasis related to prenatal exposure to
      methamphetamine. Methamphetamine is considered the fastest-growing illicit drug
      in United States. Hence, prenatal exposure to methamphetamine is expected to
      rise. Healthcare providers should become aware of the possibility of
      methamphetamine effect on the fetal liver. Raising awareness of the expectant
      mothers through the healthcare profession may reduce the risk of this condition.

PMID- 18633334
TI  - Gastroenterologists' patient instructions for oral sodium phosphate solution for
      colonoscopy preparation: a survey among gastroenterologists in the state of
      Indiana.
AB  - BACKGROUND: Oral sodium phosphate solution (OSPS) has been associated with acute
      renal failure when used as a bowel preparation for colonoscopy. AIM: To determine
      whether gastroenterologists in Indiana follow recent recommendations for safe and
      effective use of colonoscopy. METHODS: A survey of gastroenterologists in Indiana
      performed in mid-2006. Written instruction to patients were obtained and
      reviewed. RESULTS: We received responses from 97.5% of Indiana
      gastroenterologists, of whom 80% reported using OSPS. All using OSPS forwarded
      their written instructions. None exceeded the recommended two 45 mL doses in
      their written instructions. Although separation of the two 45 mL doses by at
      least 6 to 12 hours is recommended, 35% of physicians prescribed the 2 doses at
      intervals less than 6 hours. Only 9.7% gave specific instructions for volumes of
      fluid to be taken before the first dose. Fluid prescriptions during the
      preparation were often suboptimal according to current recommendations. Less than
      25% of physicians followed the recommendation to use carbohydrate-electrolyte
      solutions for hydration. CONCLUSIONS: Gastroenterologists in Indiana in mid-2006
      uniformly followed recommendations for maximum doses of OSPS, but recommended
      intervals for the doses and gave hydration instructions that often did not follow
      current recommendations.

PMID- 18633335
TI  - [Occurrence and pathogenicity of the family of Legionellaceae].
AB  - Legionella are widespread in natural aquatic environments and are able to exist
      in water of different temperatures, pH level, and nutrient and oxygen content.
      Their occurrence in nature can be attributed to their relationships with other
      microorganisms. When Legionella co-exist with algae and other bacteria,
      especially in biofilms, the availability of nutrients increases. They also are
      able to infect protozoa and subsequently reproduce within these organisms. As a
      result of these relationships, Legionella are protected against adverse
      conditions, including standard water disinfection techniques. Consequently, they
      are also prevalent in anthropogenic water such as drinking water, whirlpools, and
      cooling tower reservoirs. Aerosol-generating systems aid in the transmission of
      Legionella from water to the air. Human inhalation of contaminated aerosols leads
      to Legionella infection and disease outbreaks. Legionellosis in humans has
      typically been characterized as either a potentially fatal pneumonic condition,
      known as Legionnaires' disease, or an acute, self-limiting, non-pneumonic
      condition known as Pontiac fever. In addition, Legionella spp. cause
      extrapulmonary infection, especially in immunosuppressed patients. Timely
      treatment of Legionnaires' disease is extremely important for the patient's
      recovery. Although erythromycin has historically been used to treat patients with
      Legionnaires' disease, newer macrolides and fluoroquinolones are gaining
      acceptance as the first choice for treatment. Although 52 species of Legionella
      are known, Legionella pneumophila serogroup 1 is responsible for more than 80% of
      hospital- and community-acquired cases of Legionnaires' disease.

PMID- 18633336
TI  - Jouberin localizes to collecting ducts and interacts with nephrocystin-1.
AB  - Joubert syndrome and related disorders are autosomal recessive multisystem
      diseases characterized by cerebellar vermis aplasia/hypoplasia, retinal
      degeneration and cystic kidney disease. There are five known genes; mutations of
      which give rise to a spectrum of renal cystic diseases the most common of which
      is nephronophthisis, a disorder characterized by early loss of urinary
      concentrating ability, renal fibrosis, corticomedullary cyst formation and renal
      failure. Many of the proteins encoded by these genes interact with one another
      and are located at adherens junctions or the primary cilia and or basal bodies.
      Here we characterize Jouberin, a multi-domain protein encoded by the AHI1 gene.
      Immunohistochemistry with a novel antibody showed that endogenous Jouberin is
      expressed in brain, kidney and HEK293 cells. In the kidney, Jouberin co-localized
      with aquaporin-2 in the collecting ducts. We show that Jouberin interacts with
      nephrocystin-1 as determined by yeast-2-hybrid system and this was confirmed by
      exogenous and endogenous co-immunoprecipitation in HEK293 cells. Jouberin is
      expressed at cell-cell junctions, primary cilia and basal body of mIMCD3 cells
      while a Jouberin-GFP construct localized to centrosomes in subconfluent and
      dividing MDCK cells. Our results suggest that Jouberin is a protein whose
      expression pattern supports both the adherens junction and the ciliary hypotheses
      for abnormalities leading to nephronophthisis.

PMID- 18633337
TI  - C3 deposition glomerulopathy due to a functional factor H defect.

PMID- 18633338
TI  - Unusual case of recurrent renal artery stenosis: lessons to learn.

PMID- 18633339
TI  - Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from
      hypothesis to novel therapeutics.
AB  - In chronic kidney disease, functional impairment correlates with
      tubulointerstitial fibrosis characterised by inflammation, accumulation of
      extracellular matrix, tubular atrophy and rarefaction of peritubular capillaries.
      Loss of the microvasculature implies a hypoxic milieu and suggested an important
      role for hypoxia when the "chronic hypoxia hypothesis" was proposed a decade ago
      as an explanation for the progressive nature of fibrosis. Recent data in man
      provide evidence of decreased renal oxygenation in chronic kidney disease while
      more direct support for a causal role comes from data in rodent models showing
      that the decline in renal oxygenation precedes matrix accumulation, suggesting
      hypoxia may both initiate and promote the fibrotic response. Indeed, in vitro
      studies show that hypoxia can induce pro-fibrotic changes in tubulointerstitial
      cells. Additional postulated roles for hypoxia in chronic kidney disease are the
      sustaining of the inflammatory response, the recruitment, retention and
      differentiation towards a pro-fibrotic phenotype of circulating progenitor cells
      and the alteration of the function of intrinsic stem cell populations. Given that
      accumulating data suggests that chronic hypoxia is a final common pathway to end
      stage renal disease, therapeutic strategies that target hypoxia may be of benefit
      in retarding progression. Normalisation of microvascular tone, administration of
      pro-angiogenic factors to restore microvasculature integrity, activation of
      hypoxia-inducible transcription factors and hypoxia-mediated targeting and
      mobilisation of progenitor cells are all potential targets for future therapy.
      The limited success of existing strategies in retarding chronic kidney disease
      mandates that these new avenues of treatment be explored.

PMID- 18633340
TI  - Pre-existing renal disease promotes sepsis-induced acute kidney injury and
      worsens outcome.
AB  - While it is known that risk of death from sepsis is higher in patients with pre
      existing chronic kidney disease its mechanism is unknown. To study this we
      established a two-stage mouse model where renal disease was first induced by
      folic acid injection followed by sub-lethal cecal ligation and puncture to induce
      sepsis. Septic mice with pre-existing renal disease had significantly higher
      mortality, serum creatinine, vascular permeability, plasma vascular endothelial
      growth factor (VEGF) levels, bacteremia, serum IL-10, splenocyte apoptosis and
      more severe septic shock when compared to septic mice without pre-existing
      disease. To evaluate the contribution of vascular and immunological dysfunction,
      we treated the folate-septic mice with soluble Flt-1 to bind VEGF and chloroquine
      to reduce splenocyte apoptosis. These treatments together resulted in a
      significant improvement in kidney injury, hemodynamics and survival. Our study
      shows that the sequential mouse model mimics human sepsis frequently complicated
      by pre-existing renal disease and might be useful in evaluating preventive and
      therapeutic strategies.

PMID- 18633341
TI  - Effects of uremia and inflammation on growth hormone resistance in patients with
      chronic kidney diseases.
AB  - Resistance to the anabolic action of growth hormone may contribute to the loss of
      strength and muscle mass in adult patients with chronic kidney disease. We tested
      this hypothesis by infusing growth hormone in patients to levels necessary to
      saturate hormone receptors. This led to a significant decrease of plasma
      potassium and amino acid levels in control and hyperkalemic patients with chronic
      kidney disease. These effects were completely or partially blunted in patients
      with elevated C-reactive protein levels. In forearm perfusion studies, growth
      hormone caused a further decrease in the negative potassium and protein balance
      of hemodialysis patients without inflammation but no effect was seen in patients
      with inflammation. Only IL-6 levels and age were found to be independent
      correlates in these growth hormone-induced variations in plasma potassium and
      blood amino acids. This shows that although a resistance to pharmacologic doses
      of growth hormone is not a general feature of patients with chronic kidney
      disease, there is a subgroup characterized by blunted growth hormone action. Our
      results support the hypothesis that uremia with inflammation, but not uremia per
      se, inhibits downstream growth hormone signaling contributing to muscle atrophy.

PMID- 18633342
TI  - Oral active vitamin D is associated with improved survival in hemodialysis
      patients.
AB  - Injection of active vitamin D is associated with better survival of patients
      receiving chronic hemodialysis. Since in many countries oral active vitamin D
      administration is the most common form of treatment for secondary
      hyperparathyroidism we determined the survival benefit of oral active vitamin D
      in hemodialysis patients from six Latin America countries (FME Register as part
      of the CORES study) followed for a median of 16 months. Time-dependent Cox
      regression models, after adjustment for potential confounders, showed that the
      7,203 patients who received oral active vitamin D had significant reductions in
      overall, cardiovascular, infectious and neoplastic mortality compared to the
      8,801 patients that had not received vitamin D. Stratified analyses found a
      survival advantage in the group that had received oral active vitamin D in 36 of
      the 37 strata studied including that with the highest levels of serum calcium,
      phosphorus and parathyroid hormone. The survival benefit of oral active vitamin D
      was seen in those patients receiving mean daily doses of less than 1 microg with
      the highest reduction associated with the lowest dose. Our study shows that
      hemodialysis patients receiving oral active vitamin D had a survival advantage
      inversely related to the vitamin dose.

PMID- 18633343
TI  - Ex vivo carbon monoxide prevents cytochrome P450 degradation and
      ischemia/reperfusion injury of kidney grafts.
AB  - Renal ischemia/reperfusion injury is a major complication of kidney
      transplantation. We tested if ex vivo delivery of carbon monoxide (CO) to the
      kidney would ameliorate the renal injury of cold storage that can complicate
      renal transplantation. Orthotopic syngeneic kidney transplantation was performed
      in Lewis rats following 24 h of cold preservation in University of Wisconsin
      solution equilibrated without or with CO (soluble CO levels about 40 microM).
      Ischemia/reperfusion injury in control grafts resulted in an early upregulation
      of inflammatory mediator mRNAs and progressive deterioration of graft function.
      In contrast, the grafts preserved with CO had significantly less oxidative injury
      and this was associated with improved recipient survival compared to the control
      group. Renal injury in the control group showed considerable degradation of
      cytochrome P450 heme proteins, active heme metabolism and increased detrimental
      intracellular free heme levels. Kidney grafts preserved in CO-equilibrated
      solution maintained their cytochrome P450 protein levels, had normal
      intracellular heme levels and had less lipid peroxidation. Our results show that
      CO-mediated suppression of injurious heme-derived redox reactions offers
      protection of kidney grafts from cold ischemia/reperfusion injury.

PMID- 18633344
TI  - Retrospective tissue typing of the kidney donor from recipient urine.
AB  - Given that it is possible to extract DNA from the urine of kidney transplant
      donors and recipients we studied whether the donor HLA type can be determined
      from recipient urine. This would be useful especially when there is limited
      information on donors or when the transplant was performed long ago when tissue
      typing was less precise. We extracted and purified DNA from fresh urine and used
      the standard HLA class I and class II PCR-SSP assays comparing the findings to
      those obtained from peripheral blood of donor and recipient HLA types. Using the
      urine of 31 renal transplant recipients we assayed for the 140 known mismatches,
      and all were detected in technically successful assays with only a single false
      positive. This shows that urine samples of transplant recipients can be used to
      generate historical HLA typing information of the donor thereby aiding post
      transplant immunologic monitoring.

PMID- 18633345
TI  - A new approach in organ preservation: potential role of new polymers.
AB  - The storage conditions of the donor kidney may influence the deleterious
      consequences of ischemia/reperfusion (IR), which remains a major source of
      complications in clinical practice. Delayed graft function (DGF), seen in 20% to
      50% of transplanted cadaver kidneys, is a major risk factor affecting early and
      long-term graft survival, patient management, and costs of transplantation. Cold
      preservation plays a key role in this process and is based on hypothermia and
      high potassium solutions. In this review, the authors focused on the major
      molecular mechanisms of cold storage (CS) injury at the cellular level, which
      have been recently evidenced with modern biochemical and cell biologic methods.
      These newly uncovered aspects of cold preservation injury are often not fully
      addressed by preservation solutions in current clinical practice. The role of new
      molecules such as polyethylene glycol (PEG) is presented and their properties are
      analyzed in the organ preservation context. PEG improves organ function recovery
      and reduces inflammation and fibrosis development in several models. Because
      organs shortage is also a real public health problem, organs from non-heart
      beating donors or marginal donors are now used to expand pool of organs. As a
      consequence, the development of better organ preservation methods remains a major
      target and deserves scientific consideration.

PMID- 18633346
TI  - Survival analysis: time-dependent effects and time-varying risk factors.
AB  - In traditional Kaplan-Meier or Cox regression analysis, usually a risk factor
      measured at baseline is related to mortality thereafter. During follow-up,
      however, things may change: either the effect of a fixed baseline risk factor may
      vary over time, resulting in a weakening or strengthening of associations over
      time, or the risk factor itself may vary over time. In this paper, short-term
      versus long-term effects (so-called time-dependent effects) of a fixed baseline
      risk factor are addressed. An example is presented showing that underweight is a
      strong risk factor for mortality in dialysis patients, especially in the short
      run. In contrast, overweight is a risk factor for mortality, which is stronger in
      the long run than in the short run. In addition, the analysis of how time-varying
      risk factors (so-called time-dependent risk factors) are related to mortality is
      demonstrated by paying attention to the pitfall of adjusting for sequelae. The
      proper analysis of effects over time should be driven by a clear research
      question. Both kinds of research questions, that is those of time-dependent
      effects as well those of time-dependent risk factors, can be analyzed with time
      dependent Cox regression analysis. It will be shown that using time-dependent
      risk factors usually implies focusing on short-term effects only.

PMID- 18633347
TI  - WNT/beta-catenin signaling in nephron progenitors and their epithelial progeny.
AB  - WNT signaling is a fundamental molecular pathway in both embryogenesis and
      disease. Nephron development is dependent on WNT signaling. The nephron epithelia
      proximal to the collecting duct develop from progenitor cells in the metanephric
      mesenchyme. The process involves formation of proto-epithelial cell aggregates,
      conversion into epithelia, and proximal-distal patterning of the nephron. Two
      ligands from the WNT family, namely Wnt9b and Wnt4, are required for nephron
      differentiation. Recent studies have addressed the downstream targets of these
      WNT ligands and delineated the role of the canonical WNT signaling pathway. This
      pathway depends on the intracellular protein beta-catenin and the T cell-specific
      transcription factor/lymphoid enhancer factor-1 (TCF/Lef1) family of
      transcription factors. Selective beta-catenin signaling antagonism inhibits
      differentiation of metanephric mesenchymal progenitor cells, while forced
      activation triggers a stage progression towards proto-epithelial aggregates.
      Nonetheless, activation of the pathway is transient during epithelial
      differentiation and titration of pathway activity may be central for the proper
      coordination of differentiation and morphogenesis. We review current evidence on
      the WNT/beta-catenin/TCF/Lef1 signaling pathway in kidney epithelial development
      and discuss the potential implication of non-canonical WNT signaling and WNT
      independent events.

PMID- 18633349
TI  - Molecular basis of the copulatory plug polymorphism in Caenorhabditis elegans.
AB  - Heritable variation is the raw material for evolutionary change, and
      understanding its genetic basis is one of the central problems in modern biology.
      We investigated the genetic basis of a classic phenotypic dimorphism in the
      nematode Caenorhabditis elegans. Males from many natural isolates deposit a
      copulatory plug after mating, whereas males from other natural isolates?including
      the standard wild-type strain (N2 Bristol) that is used in most research
      laboratories?do not deposit plugs. The copulatory plug is a gelatinous mass that
      covers the hermaphrodite vulva, and its deposition decreases the mating success
      of subsequent males. We show that the plugging polymorphism results from the
      insertion of a retrotransposon into an exon of a novel mucin-like gene, plg-1,
      whose product is a major structural component of the copulatory plug. The gene is
      expressed in a subset of secretory cells of the male somatic gonad, and its loss
      has no evident effects beyond the loss of male mate-guarding. Although C. elegans
      descends from an obligate-outcrossing, male?female ancestor, it occurs primarily
      as self-fertilizing hermaphrodites. The reduced selection on male?male
      competition associated with the origin of hermaphroditism may have permitted the
      global spread of a loss-of-function mutation with restricted pleiotropy.

PMID- 18633350
TI  - The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh
      signalling.
AB  - The intestinal tract maintains proper function by replacing aged cells with
      freshly produced cells that arise from a population of self-renewing intestinal
      stem cells (ISCs). In the mammalian intestine, ISC self renewal, amplification
      and differentiation take place along the crypt-villus axis, and are controlled by
      the Wnt and hedgehog (Hh) signalling pathways. However, little is known about the
      mechanisms that specify ISCs within the developing intestinal epithelium, or
      about the signalling centres that help maintain them in their self-renewing stem
      cell state. Here we show that in adult Drosophila melanogaster, ISCs of the
      posterior intestine (hindgut) are confined to an anterior narrow segment, which
      we name the hindgut proliferation zone (HPZ). Within the HPZ, self renewal of
      ISCs, as well as subsequent proliferation and differentiation of ISC descendants,
      are controlled by locally emanating Wingless (Wg, a Drosophila Wnt homologue) and
      Hh signals. The anteriorly restricted expression of Wg in the HPZ acts as a niche
      signal that maintains cells in a slow-cycling, self-renewing mode. As cells
      divide and move posteriorly away from the Wg source, they enter a phase of rapid
      proliferation. During this phase, Hh signal is required for exiting the cell
      cycle and the onset of differentiation. The HPZ, with its characteristic
      proliferation dynamics and signalling properties, is set up during the embryonic
      phase and becomes active in the larva, where it generates all adult hindgut cells
      including ISCs. The mechanism and genetic control of cell renewal in the
      Drosophila HPZ exhibits a large degree of similarity with what is seen in the
      mammalian intestine. Our analysis of the Drosophila HPZ provides an insight into
      the specification and control of stem cells, highlighting the way in which the
      spatial pattern of signals that promote self renewal, growth and differentiation
      is set up within a genetically tractable model system.

PMID- 18633351
TI  - Internal brain state regulates membrane potential synchrony in barrel cortex of
      behaving mice.
AB  - Internal brain states form key determinants for sensory perception, sensorimotor
      coordination and learning. A prominent reflection of different brain states in
      the mammalian central nervous system is the presence of distinct patterns of
      cortical synchrony, as revealed by extracellular recordings of the
      electroencephalogram, local field potential and action potentials. Such temporal
      correlations of cortical activity are thought to be fundamental mechanisms of
      neuronal computation. However, it is unknown how cortical synchrony is reflected
      in the intracellular membrane potential (V(m)) dynamics of behaving animals. Here
      we show, using dual whole-cell recordings from layer 2/3 primary somatosensory
      barrel cortex in behaving mice, that the V(m) of nearby neurons is highly
      correlated during quiet wakefulness. However, when the mouse is whisking, an
      internally generated state change reduces the V(m) correlation, resulting in a
      desynchronized local field potential and electroencephalogram. Action potential
      activity was sparse during both quiet wakefulness and active whisking. Single
      action potentials were driven by a large, brief and specific excitatory input
      that was not present in the V(m) of neighbouring cells. Action potential
      initiation occurs with a higher signal-to-noise ratio during active whisking than
      during quiet periods. Therefore, we show that an internal brain state dynamically
      regulates cortical membrane potential synchrony during behaviour and defines
      different modes of cortical processing.

PMID- 18633352
TI  - Acetylcholine contributes through muscarinic receptors to attentional modulation
      in V1.
AB  - Attention exerts a strong influence over neuronal processing in cortical areas.
      It selectively increases firing rates and affects tuning properties, including
      changing receptive field locations and sizes. Although these effects are well
      studied, their cellular mechanisms are poorly understood. To study the cellular
      mechanisms, we combined iontophoretic pharmacological analysis of cholinergic
      receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca
      mulatta) performed a task that demanded top-down spatial attention. Attending to
      the receptive field of the V1 neuron under study caused an increase in firing
      rates. Here we show that this attentional modulation was enhanced by low doses of
      acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine
      reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had
      no systematic effect. These results demonstrate that muscarinic cholinergic
      mechanisms play a central part in mediating the effects of attention in V1.

PMID- 18633353
TI  - On the nature of partial agonism in the nicotinic receptor superfamily.
AB  - Partial agonists are ligands that bind to receptors but produce only a small
      maximum response even at concentrations where all receptors are occupied. In the
      case of ligand-activated ion channels, it has been supposed since 1957 that
      partial agonists evoke a small response because they are inefficient at eliciting
      the change of conformation between shut and open states of the channel. We have
      investigated partial agonists for two members of the nicotinic superfamily-the
      muscle nicotinic acetylcholine receptor and the glycine receptor-and find that
      the open-shut reaction is similar for both full and partial agonists, but the
      response to partial agonists is limited by an earlier conformation change
      ('flipping') that takes place while the channel is still shut. This has
      implications for the interpretation of structural studies, and in the future, for
      the design of partial agonists for therapeutic use.

PMID- 18633354
TI  - The scientific contributions of M. Judah Folkman to cancer research.
AB  - Dr Judah Folkman was frequently described as a highly compassionate physician who
      served his patients not only by performing surgery and offering them comfort and
      reassurance, but also by working tirelessly in the laboratory to find new
      approaches to the treatment of disease. His dedication to understanding the role
      of angiogenesis, the formation of new blood vessels, in human disease has given
      rise to new treatments for several diseases, including inflammatory diseases,
      vision-threatening diseases of the eye and, as will be emphasized in this
      Perspective, cancer.

PMID- 18633355
TI  - The role of myeloid cells in the promotion of tumour angiogenesis.
AB  - The use of various transgenic mouse models and analysis of human tumour biopsies
      has shown that bone marrow-derived myeloid cells, such as macrophages,
      neutrophils, eosinophils, mast cells and dendritic cells, have an important role
      in regulating the formation and maintenance of blood vessels in tumours. In this
      Review the evidence for each of these cell types driving tumour angiogenesis is
      outlined, along with the mechanisms regulating their recruitment and activation
      by the tumour microenvironment. We also discuss the therapeutic implications of
      recent findings that specific myeloid cell populations modulate the responses of
      tumours to agents such as chemotherapy and some anti-angiogenic therapies.

PMID- 18633356
TI  - Structural comparisons of class I phosphoinositide 3-kinases.
AB  - Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell
      growth. One of these kinases, PI3Kalpha, is frequently mutated in diverse tumour
      types. The recently determined structure of PI3Kalpha reveals features that
      distinguish this enzyme from related lipid kinases. In addition, wild-type
      PI3Kgamma differs from PI3Kalpha by a substitution identical to a PI3Kalpha
      oncogenic mutant (His1047Arg) that might explain the differences in the enzymatic
      activities of the normal and mutant PI3Kalpha. Comparison of the PI3K structures
      also identified structural features that could potentially be exploited for the
      design of isoform-specific inhibitors.

PMID- 18633357
TI  - Testosterone therapy in hypogonadal men and potential prostate cancer risk: a
      systematic review.
AB  - This paper provides a systematic review of the literature about prostate cancer
      risk associated with testosterone therapy for hypogonadism. A comprehensive
      search of MEDLINE, EMBASE and other resources was conducted to identify articles
      that highlight occurrences of prostate cancer in men receiving testosterone
      therapy for hypogonadism treatment. Articles that met study inclusion criteria
      were assessed for causality between testosterone treatment and prostate cancer,
      increased prostate-specific antigen or abnormal digital rectal examination
      findings. Of 197 articles relating to testosterone therapy, 44 met inclusion
      criteria: 11 placebo-controlled, randomized studies; 29 non-placebo-controlled
      studies of men with no prostate cancer history; and 4 studies of hypogonadal men
      with history of prostate cancer. Of studies that met inclusion criteria, none
      demonstrated that testosterone therapy for hypogonadism increased prostate cancer
      risk or increased Gleason grade of cancer detected in treated vs untreated men.
      Testosterone therapy did not have a consistent effect on prostate-specific
      antigen levels.

PMID- 18633361
TI  - Templeton's legacy.

PMID- 18633363
TI  - An uneasy peace.

PMID- 18633362
TI  - Life after SuperBabe.

PMID- 18633370
TI  - A physicist links magnetism, force and fatigue.

PMID- 18633375
TI  - Pakistan finds two radioactive containers.

PMID- 18633376
TI  - Russia delays Lake Vostok drill.

PMID- 18633377
TI  - Autism study panned by critics.

PMID- 18633379
TI  - Starting small but adding up: a free maths archive.

PMID- 18633378
TI  - Making babies: the next 30 years.

PMID- 18633380
TI  - Irrawaddy may be poisoned by arsenic.

PMID- 18633381
TI  - Mouse miRNA library to open.

PMID- 18633390
TI  - Climate science: The long summer begins.

PMID- 18633391
TI  - Space science: From the desert to the edge of space.

PMID- 18633392
TI  - Health science: from bench to bedside to trench and back.

PMID- 18633393
TI  - Translational research: don't neglect basic science.

PMID- 18633394
TI  - Reverse translation: clearing a path from bedside to bench.

PMID- 18633401
TI  - 30 years: from IVF to stem cells.

PMID- 18633402
TI  - Developmental biology: Serpent clocks tick faster.

PMID- 18633403
TI  - Microscopy: Spot the atom.

PMID- 18633404
TI  - Motor neuron disease: The curious ways of ALS.

PMID- 18633405
TI  - Earth science: Volcanic cause of catastrophe.

PMID- 18633406
TI  - Signal transduction: Linking nutrients to growth.

PMID- 18633407
TI  - Systems biology: On the cell cycle and its switches.

PMID- 18633408
TI  - Obituary: John Templeton (1912-2008).

PMID- 18633410
TI  - Strong magnetic fields in normal galaxies at high redshift.
AB  - The origin and growth of magnetic fields in galaxies is still something of an
      enigma. It is generally assumed that seed fields are amplified over time through
      the dynamo effect, but there are few constraints on the timescale. It was
      recently demonstrated that field strengths as traced by rotation measures of
      distant (and hence ancient) quasars are comparable to those seen today, but it
      was unclear whether the high fields were in the unusual environments of the
      quasars themselves or distributed along the lines of sight. Here we report high
      resolution spectra that demonstrate that the quasars with strong Mg II absorption
      lines are unambiguously associated with larger rotation measures. Because Mg ii
      absorption occurs in the haloes of normal galaxies along the sightlines to the
      quasars, this association requires that organized fields of surprisingly high
      strengths are associated with normal galaxies when the Universe was only about
      one-third of its present age.

PMID- 18633409
TI  - Positive feedback of G1 cyclins ensures coherent cell cycle entry.
AB  - In budding yeast, Saccharomyces cerevisiae, the Start checkpoint integrates
      multiple internal and external signals into an all-or-none decision to enter the
      cell cycle. Here we show that Start behaves like a switch due to systems-level
      feedback in the regulatory network. In contrast to current models proposing a
      linear cascade of Start activation, transcriptional positive feedback of the G1
      cyclins Cln1 and Cln2 induces the near-simultaneous expression of the
      approximately 200-gene G1/S regulon. Nuclear Cln2 drives coherent regulon
      expression, whereas cytoplasmic Cln2 drives efficient budding. Cells with the
      CLN1 and CLN2 genes deleted frequently arrest as unbudded cells, incurring a
      large fluctuation-induced fitness penalty due to both the lack of cytoplasmic
      Cln2 and insufficient G1/S regulon expression. Thus, positive-feedback-amplified
      expression of Cln1 and Cln2 simultaneously drives robust budding and rapid,
      coherent regulon expression. A similar G1/S regulatory network in mammalian
      cells, comprised of non-orthologous genes, suggests either conservation of
      regulatory architecture or convergent evolution.

PMID- 18633411
TI  - Hydrated silicate minerals on Mars observed by the Mars Reconnaissance Orbiter
      CRISM instrument.
AB  - Phyllosilicates, a class of hydrous mineral first definitively identified on Mars
      by the OMEGA (Observatoire pour la Mineralogie, L'Eau, les Glaces et l'Activitie)
      instrument, preserve a record of the interaction of water with rocks on Mars.
      Global mapping showed that phyllosilicates are widespread but are apparently
      restricted to ancient terrains and a relatively narrow range of mineralogy (Fe/Mg
      and Al smectite clays). This was interpreted to indicate that phyllosilicate
      formation occurred during the Noachian (the earliest geological era of Mars), and
      that the conditions necessary for phyllosilicate formation (moderate to high pH
      and high water activity) were specific to surface environments during the
      earliest era of Mars's history. Here we report results from the Compact
      Reconnaissance Imaging Spectrometer for Mars (CRISM) of phyllosilicate-rich
      regions. We expand the diversity of phyllosilicate mineralogy with the
      identification of kaolinite, chlorite and illite or muscovite, and a new class of
      hydrated silicate (hydrated silica). We observe diverse Fe/Mg-OH phyllosilicates
      and find that smectites such as nontronite and saponite are the most common, but
      chlorites are also present in some locations. Stratigraphic relationships in the
      Nili Fossae region show olivine-rich materials overlying phyllosilicate-bearing
      units, indicating the cessation of aqueous alteration before emplacement of the
      olivine-bearing unit. Hundreds of detections of Fe/Mg phyllosilicate in rims,
      ejecta and central peaks of craters in the southern highland Noachian cratered
      terrain indicate excavation of altered crust from depth. We also find
      phyllosilicate in sedimentary deposits clearly laid by water. These results point
      to a rich diversity of Noachian environments conducive to habitability.

PMID- 18633412
TI  - Generation of Fock states in a superconducting quantum circuit.
AB  - Spin systems and harmonic oscillators comprise two archetypes in quantum
      mechanics. The spin-1/2 system, with two quantum energy levels, is essentially
      the most nonlinear system found in nature, whereas the harmonic oscillator
      represents the most linear, with an infinite number of evenly spaced quantum
      levels. A significant difference between these systems is that a two-level spin
      can be prepared in an arbitrary quantum state using classical excitations,
      whereas classical excitations applied to an oscillator generate a coherent state,
      nearly indistinguishable from a classical state. Quantum behaviour in an
      oscillator is most obvious in Fock states, which are states with specific numbers
      of energy quanta, but such states are hard to create. Here we demonstrate the
      controlled generation of multi-photon Fock states in a solid-state system. We use
      a superconducting phase qubit, which is a close approximation to a two-level spin
      system, coupled to a microwave resonator, which acts as a harmonic oscillator, to
      prepare and analyse pure Fock states with up to six photons. We contrast the Fock
      states with coherent states generated using classical pulses applied directly to
      the resonator.

PMID- 18633413
TI  - Climbing the Jaynes-Cummings ladder and observing its nonlinearity in a cavity
      QED system.
AB  - The field of cavity quantum electrodynamics (QED), traditionally studied in
      atomic systems, has gained new momentum by recent reports of quantum optical
      experiments with solid-state semiconducting and superconducting systems. In
      cavity QED, the observation of the vacuum Rabi mode splitting is used to
      investigate the nature of matter-light interaction at a quantum-mechanical level.
      However, this effect can, at least in principle, be explained classically as the
      normal mode splitting of two coupled linear oscillators. It has been suggested
      that an observation of the scaling of the resonant atom-photon coupling strength
      in the Jaynes-Cummings energy ladder with the square root of photon number n is
      sufficient to prove that the system is quantum mechanical in nature. Here we
      report a direct spectroscopic observation of this characteristic quantum
      nonlinearity. Measuring the photonic degree of freedom of the coupled system, our
      measurements provide unambiguous spectroscopic evidence for the quantum nature of
      the resonant atom-field interaction in cavity QED. We explore atom-photon
      superposition states involving up to two photons, using a spectroscopic pump and
      probe technique. The experiments have been performed in a circuit QED set-up, in
      which very strong coupling is realized by the large dipole coupling strength and
      the long coherence time of a superconducting qubit embedded in a high-quality on
      chip microwave cavity. Circuit QED systems also provide a natural quantum
      interface between flying qubits (photons) and stationary qubits for applications
      in quantum information processing and communication.

PMID- 18633414
TI  - Imaging and dynamics of light atoms and molecules on graphene.
AB  - Observing the individual building blocks of matter is one of the primary goals of
      microscopy. The invention of the scanning tunnelling microscope revolutionized
      experimental surface science in that atomic-scale features on a solid-state
      surface could finally be readily imaged. However, scanning tunnelling microscopy
      has limited applicability due to restrictions in, for example, sample
      conductivity, cleanliness, and data acquisition rate. An older microscopy
      technique, that of transmission electron microscopy (TEM), has benefited
      tremendously in recent years from subtle instrumentation advances, and individual
      heavy (high-atomic-number) atoms can now be detected by TEM even when embedded
      within a semiconductor material. But detecting an individual low-atomic-number
      atom, for example carbon or even hydrogen, is still extremely challenging, if not
      impossible, via conventional TEM owing to the very low contrast of light
      elements. Here we demonstrate a means to observe, by conventional TEM, even the
      smallest atoms and molecules: on a clean single-layer graphene membrane,
      adsorbates such as atomic hydrogen and carbon can be seen as if they were
      suspended in free space. We directly image such individual adatoms, along with
      carbon chains and vacancies, and investigate their dynamics in real time. These
      techniques open a way to reveal dynamics of more complex chemical reactions or
      identify the atomic-scale structure of unknown adsorbates. In addition, the study
      of atomic-scale defects in graphene may provide insights for nanoelectronic
      applications of this interesting material.

PMID- 18633415
TI  - Cretaceous oceanic anoxic event 2 triggered by a massive magmatic episode.
AB  - Oceanic anoxic events (OAEs) were episodes of widespread marine anoxia during
      which large amounts of organic carbon were buried on the ocean floor under oxygen
      deficient bottom waters. OAE2, occurring at the Cenomanian/Turonian boundary
      (about 93.5 Myr ago), is the most widespread and best defined OAE of the mid
      Cretaceous. Although the enhanced burial of organic matter can be explained
      either through increased primary productivity or enhanced preservation scenarios,
      the actual trigger mechanism, corresponding closely to the onset of these
      episodes of increased carbon sequestration, has not been clearly identified. It
      has been postulated that large-scale magmatic activity initially triggered OAE2
      (refs 4, 5), but a direct proxy of magmatism preserved in the sedimentary record
      coinciding closely with the onset of OAE2 has not yet been found. Here we report
      seawater osmium isotope ratios in organic-rich sediments from two distant sites.
      We find that at both study sites the marine osmium isotope record changes
      abruptly just at or before the onset of OAE2. Using a simple two-component mixing
      equation, we calculate that over 97 per cent of the total osmium content in
      contemporaneous seawater at both sites is magmatic in origin, a approximately 30
      50-fold increase relative to pre-OAE conditions. Furthermore, the magmatic osmium
      isotope signal appears slightly before the OAE2-as indicated by carbon isotope
      ratios-suggesting a time-lag of up to approximately 23 kyr between magmatism and
      the onset of significant organic carbon burial, which may reflect the reaction
      time of the global ocean system. Our marine osmium isotope data are indicative of
      a widespread magmatic pulse at the onset of OAE2, which may have triggered the
      subsequent deposition of large amounts of organic matter.

PMID- 18633416
TI  - Coherent ecological dynamics induced by large-scale disturbance.
AB  - Aggregate community-level response to disturbance is a principle concern in
      ecology because post-disturbance dynamics are integral to the ability of
      ecosystems to maintain function in an uncertain world. Community-level responses
      to disturbance can be arrayed along a spectrum ranging from synchronous
      oscillations where all species rise and fall together, to compensatory dynamics
      where total biomass remains relatively constant despite fluctuations in the
      densities of individual species. An important recent insight is that patterns of
      synchrony and compensation can vary with the timescale of analysis and that
      spectral time series methods can enable detection of coherent dynamics that would
      otherwise be obscured by opposing patterns occurring at different scales. Here I
      show that application of wavelet analysis to experimentally manipulated plankton
      communities reveals strong synchrony after disturbance. The result is paradoxical
      because it is well established that these communities contain both disturbance
      sensitive and disturbance-tolerant species leading to compensation within
      functional groups. Theory predicts that compensatory substitution of functionally
      equivalent species should stabilize ecological communities, yet I found at the
      whole-community level a large increase in seasonal biomass variation. Resolution
      of the paradox hinges on patterns of seasonality among species. The compensatory
      shift in community composition after disturbance resulted in a loss of cold
      season dominants, which before disturbance had served to stabilize biomass
      throughout the year. Species dominating the disturbed community peaked coherently
      during the warm season, explaining the observed synchrony and increase in
      seasonal biomass variation. These results suggest that theory relating
      compensatory dynamics to ecological stability needs to consider not only
      complementarity in species responses to environmental change, but also seasonal
      complementarity among disturbance-tolerant and disturbance-sensitive species.

PMID- 18633418
TI  - How to interpret your dot: decoding the message of clinical performance
      indicators.
AB  - Comparative performance reports continue to proliferate, so it is increasingly
      important that healthcare workers can interpret the graphically displayed results
      correctly. This article acquaints readers with key concepts for thinking clearly
      and critically about such displays: (1) articulating the question a display
      answers, along with reflecting on questions the display might appear to, but does
      not, answer; (2) establishing that provider comparisons are made fairly, ever
      mindful of methodological assumptions and limitations; (3) accounting for
      systematic differences among performers that are unexplained by specified
      predictors, that is, random effect methods that yield 'shrunken' estimates; (4)
      understanding funnel plots used to summarize complex analyses and how one may
      vary the interrogative focus so that 'outlier' values most likely signal
      extraordinary performance. Finally, these concepts are given broader context in a
      view of the ultimate aim of the evaluative enterprise.

PMID- 18633419
TI  - Gestational diabetes: diagnosis and management.
AB  - PURPOSE: To review the diagnosis and management of gestational diabetes.
      EPIDEMIOLOGY: In the United States, approximately 2 to 5% of all pregnant women
      have gestational diabetes. Those women with a family history of type 2 diabetes
      mellitus, Asian or native American race, Latina ethnicity or obesity are at
      higher risk for developing gestational diabetes. CONCLUSION: Women with
      gestational diabetes who are treated appropriately can achieve good outcomes in
      the majority of pregnancies. Frequent blood glucose monitoring, nutrition
      counseling and frequent physician contact allow for individualized care to
      achieve optimal outcomes. Such treatment includes diet, exercise and insulin. The
      use of oral hypoglycemic agents is controversial and there is some concern about
      worse maternal and neonatal outcomes as compared to treatment with insulin.
      Evolving technologies promise to provide more therapeutic options.

PMID- 18633420
TI  - Effects of motor physical therapy on bone mineralization in premature infants: a
      randomized controlled study.
AB  - OBJECTIVE: To study the effect of physical therapy on bone mineralization, weight
      gain and growth in preterm infants. METHOD: After fulfilling the inclusion
      criteria, preterm infants were matched for gestational age and birth weight and
      then randomly assigned to the physiotherapy group (PG, n=15) and control group
      (CG, n=14). The PG received motor physical therapy for 15 min daily, 5 times per
      week until hospital discharge. Bone mineralization was measured by total body
      dual energy X-ray beam absorptiometry (DEXA) at the onset and end of the study.
      Statistical analysis was realized by ANCOVA and linear correlation tests. RESULT:
      The physical therapy group (PG) presented greater body weight gain per day
      (27.4+/-2.4 vs 21.01+/-4.4 g, P<0.001) and length (1.3+/-0.3 vs 0.8+/-0.2 cm
      week(-1), P<0.001) than did the control group (CG). Body composition values
      verified by DEXA were greater for the PG. The mean gain in bone mineral content
      (BMC) (mg) was greater in the PG (434+/-247.5 vs -8.9+/-11.4, P<0.001), as was
      the mean bone mineral density (BMD) gain (mg cm(-2)) (8.4+/-5.6 vs -3.1+/-5.5,
      P<0.001). The gain in bone area (BA,cm(2)) was 10.3+/-5 in the PG vs 1.5 +/-2 in
      the CG (P<0.001). The gain in lean mass (LM) (g) in the PG was also greater than
      in the CG (271.1+/-21.4 vs 109.1+/-1.0, P<0.009). The fat mass (g) was similar
      between the groups (P=0.432). CONCLUSION: These results showed that physiotherapy
      in preterm infants produced greater gains in growth, body weight, BMC, BMD, BA
      and LM.

PMID- 18633421
TI  - Massage therapy reduces hospital stay and occurrence of late-onset sepsis in very
      preterm neonates.
AB  - OBJECTIVE: To study the effect of maternal massage therapy on hospital stay in
      very-low-birth-weight infants who were already submitted to skin-to-skin care.
      STUDY DESIGN: A randomized study was performed including infants of birth weight
      >or=750 and <or=1500 g and gestational age <or=32 weeks. The exclusion criteria
      were as follows: death before completing 48 h and presence of major
      malformations. Neonates were divided into intervention group (IG) (standard care
      plus maternal massage) and control group (CG). Anthropometric data were always
      verified by a person blind to the group to which the newborn belonged. Maternal
      massage was performed four times a day on the face and limbs. Passive exercises
      of upper and lower limbs were also done by the mothers. RESULT: A total of 104
      newborns were included, 52 in each group. Both groups were similar in gestational
      age (IG: 29.7+/-1.6; CG: 29.4+/-1.6 weeks), birth weight (IG: 1186+/-194; CG:
      1156+/-198 g), gender, number of small-for-gestational-age infants, SNAPPE-II,
      deaths, gains in weight, length and head circumference. Incidence of late-onset
      sepsis was significantly lower in the intervention group (IG: 10.8%, n=5; CG:
      38.3%, n=18; P=0.005). IG was discharged from the hospital 7 days before CG (IG:
      42, confidence interval (CI) 95%: 38 to 46; CG: 49, CI 95%: 42 to 56), and
      presented 1.85 hazard ratio (CI 95%: 1.09 to 3.13; P=0.023) for early discharge.
      CONCLUSION: Maternal massage therapy in very-low-birth-weight infants decreases
      the length of hospital stay and the incidence of late-onset neonatal sepsis.

PMID- 18633422
TI  - Nobody likes premies: the relative value of patients' lives.
AB  - OBJECTIVE: The objective of this study was to examine whether patient selection
      or triage requires placing a relative value on human lives and whether the values
      placed on these lives are consistent with current ethical theories. STUDY DESIGN:
      An anonymous questionnaire was administered to groups of physicians and students
      in Montreal. It presented eight currently incompetent patients with potential
      neurological sequelae requiring emergency care. Predicted outcomes were
      explicitly described. Four patients had a predicted 50% survival and a 50% chance
      of impairment; they were a preterm and a term neonate, a 2-month-old and a 50
      year-old. Two already disabled patients, a 7-year-old and an 80-year-old, had 50%
      predicted survival. A 14-year-old and a 35-year-old had 5% survival, but
      differing impairment. Respondents were asked if they would resuscitate and in
      what order they would resuscitate if all needed intervention simultaneously.
      RESULT: Eighty-five percent response rate, n=524. The proportion stating they
      would always resuscitate was smallest for the 80-year-old (18% P<0.001 compared
      to other patients), then the preterm (35%, P<0.001), then the term and the 50
      year-old (53 and 58%, P<0.01). The 2-month-old and the 7-year-old would be
      resuscitated most frequently (74 and 77%, P<0.01), followed by the patients with
      5% survival (64 and 68%, P<0.001). The median order of triage was first the 2
      month-old, followed by the 7-year-old, the 14-year-old, the term newborn, the 50
      year-old, the 35-year-old, the premature newborn and the 80-year-old. CONCLUSION:
      Order of resuscitation was not closely related to the predicted survival,
      impairment or potential life years gained. Age appeared to have a strong
      influence, with children's lives being valued more than the adults'. This
      tendency was reversed for the newborn infants who were undervalued compared with
      older children, and most particularly for the premature. The value placed on the
      life of newborns, in particular the premature, is less than that expected by any
      objective medical data and was not consistent with any ethical theory that we
      tested.

PMID- 18633423
TI  - Does point-of-care functional echocardiography enhance cardiovascular care in the
      NICU?
AB  - Although the last two decades have seen major advances in the care of sick,
      extremely premature newborns, the approach to cardiovascular assessment and
      monitoring remains suboptimal owing to an overreliance on poorly predictive
      clinical markers such as heart rate or capillary refill time. Point-of-care
      functional echocardiography (PCFecho) enables real-time evaluation of cardiac
      performance and systemic hemodynamics to characterize acute physiology, identify
      the exact nature of cardiovascular compromise and guide therapeutic decisions. In
      this article, we will review four clinical scenarios where bedside functional
      cardiac imaging enabled delineation of the real clinical problem and refinement
      of the therapeutic care plan with direct patient benefits.

PMID- 18633425
TI  - Interacting effect of genetic variants of angiotensin II type 1 receptor on
      susceptibility to essential hypertension in Northern Han Chinese.

PMID- 18633424
TI  - A transmembrane polymorphism in FcgammaRIIb (FCGR2B) is associated with the
      production of anti-cyclic citrullinated peptide autoantibodies in Taiwanese RA.
AB  - The aim of the current study was to determine whether the FcgammaRIIb 187-Ile/Thr
      polymorphism is a predisposition factor for subtypes of RA defined by disease
      severity and production of autoantibodies against cyclic citrullinated peptides
      (anti-CCPs) in Taiwanese RA patients. Genotype distributions and allele
      frequencies of FcgammaRIIb 187-Ile/Thr were compared between 562 normal healthy
      controls and 640 RA patients as stratified by clinical parameters and
      autoantibodies. Significant enrichment of 187-Ile allele was observed in RA
      patients positive for anti-CCP antibodies as compared with the anti-CCP negative
      RA patients (P=0.001, OR 1.652 (95% CI 1.210-2.257)) or as compared with the
      normal controls (P=0.005, OR 1.348 (95% CI 1.092-1.664)). In addition, 187-Ile
      allele was found to be enriched in RA patients positive for rheumatoid factor
      (RF) compared to the RF negative RA patients (P=0.024, OR 1.562 (95% CI 1.059
      2.303)). Furthermore, the homozygotes were enriched in destructive male RA
      patients (P=0.035; OR 2.038 (95% CI 1.046-3.973)) and the 187-Ile allele was
      associated with early-onset of RA in Taiwanese patients (P=0.045, OR 1.548 (95%
      CI 1.007-2.379)). Thus, FcgammaRIIb SNP 187-Ile/Thr may influence the RA
      phenotypes in Taiwanese RA.

PMID- 18633426
TI  - Cost-effectiveness of irbesartan/hydrochlorothiazide in patients with
      hypertension: an economic evaluation for Sweden.
AB  - Irbesartan, an angiotensin-II inhibitor, has been shown to be an effective
      antihypertensive agent in clinical trials. The purpose of this study was to
      assess the cost-effectiveness of irbesartan in combination with
      hydrochlorothiazide (HCTZ) in Swedish health-care setting by predicting clinical
      events and life years based upon observed reductions in blood pressure in
      clinical trials. The cost-effectiveness of antihypertensive treatment with
      irbesartan compared with placebo and to other selected angiotensin-II inhibitors
      (losartan, valsartan, candesartan) in combination with HCTZ was estimated using a
      Markov model. The incidence of cardiovascular disease was obtained from the
      Swedish inpatient registry, whereas the risk reductions associated with
      antihypertensive therapy were taken from the medical literature. Costs for
      antihypertensive therapy and for treatment of cardiovascular events were
      included, and the health effects were measured in terms of quality-adjusted life
      years (QALYs). The study was conducted from a health-care payer perspective. For
      a 55-year-old male, irbesartan 150 mg/HCTZ 12.5 mg was a dominant strategy
      (better health effects at lower costs) when compared with losartan 50 mg/HCTZ
      12.5 mg and valsartan 80 mg/HCTZ 12.5 mg, and the cost-effectiveness ratio
      compared with placebo was 3500 euros per QALY gained. In moderate-to-severe
      hypertension, irbesartan was cost-effective compared with losartan, whereas the
      results compared with candesartan were mixed. High-dose combination therapy of
      irbesartan was also found to be cost-effective compared with low-dose combination
      therapy. The results from the model indicate that irbesartan provides a cost
      effective antihypertensive treatment strategy compared with both placebo, and to
      valsartan and losartan.

PMID- 18633427
TI  - Association of aortic valve sclerosis with thrombin generation in hypertensive
      patients.
AB  - Aortic valve sclerosis (AVS) may predispose to a prothrombotic state, as AVS is
      predictor of cardiovascular events in hypertensive populations. Thrombin exerts
      non-thrombotic effects such as vessel tone regulation, progression of
      atherosclerosis and stimulation of atrial natriuretic peptide (ANP) secretion. We
      hypothesized that hypertensive patients with AVS may have a persistently
      activated thrombin generation. We studied 234 asymptomatic never-treated
      hypertensive patients (73 of them with AVS). Prothrombin F1+2 (F1+2), as a marker
      of thrombin generation and fibrin D-dimer, as a marker of thrombus formation, ANP
      and brain natriuretic peptide (BNP) were measured. Presence of AVS, aortic jet
      velocity and left ventricular diameter at diastole were determined by
      echocardiography. Glomerular filtration rate was estimated using the Modification
      of Diet in Renal Disease formula. F1+2 (median and interquartile range (IQR) =
      1.05, 0.87-1.38 nM vs. 0.93, 0.72-1.16) and ANP (22, 14-37 pg ml(-1) vs. 17, 11
      25) levels were greater, and glomerular filtration rate values (65+/-9 ml min(
      1)/1.73 m2 vs. 68+/-11) were lower in hypertensive patients with AVS than in
      those without AVS. F1+2 (odds ratio, 95% CI = 2.94, 1.07-8.6) was independently
      associated with AVS after being adjusted for age, gender and the variables of
      cardiorenal functions measured. After 6 months of treatment using valsartan, F1+2
      levels remained elevated in hypertensive patients with AVS (1.14, 0.83-1.42 nM
      vs. 1.07, 0.84-1.5, n=19), but decreased in those without AVS (1.01, 0.85-1.31
      vs. 0.8, 0.84-1.78, n=27). Thrombin generation was associated with AVS in
      untreated hypertensive patients, and this association was persistent after blood
      pressure-lowering treatment using valsartan.

PMID- 18633428
TI  - The pressure of finding human hypertension genes: new tools, old dilemmas.
AB  - Researchers in hypertension genetics feel like they are left behind again. It
      always seems that the 'other' complex diseases are ahead in the race. Evolving
      new technologies in the form of genome-wide arrays and 'omics' technologies mean
      that investigators can now potentially identify many novel disease factors in one
      large-scale experiment. Hypertension research now faces the challenge of where to
      go next after the first genome-wide association experiments failed to provide
      robust candidates. In this review, we contemplate the old dilemma of whether such
      genes may ever be found; however, we believe advancing technologies and
      plummeting costs of large-scale experiments will contribute to the identification
      of novel molecules that underlie essential hypertension.

PMID- 18633429
TI  - Rapid diagnosis of ataxia-telangiectasia by flow cytometric monitoring of DNA
      damage-dependent ATM phosphorylation.

PMID- 18633430
TI  - A novel arsenical has antitumor activity toward As2O3-resistant and MRP1/ABCC1
      overexpressing cell lines.
AB  - Inorganic arsenic trioxide (As(2)O(3)) is a highly effective treatment for acute
      promyelocytic leukemia (APL). However, other cancers do not respond well to this
      form of arsenic at clinically achievable doses. We tested a novel arsenical, S
      dimethylarsino-glutathione (darinaparsin) for efficacy in various malignancies in
      vitro. Darinaparsin is significantly more potent than As(2)O(3) at mediating
      apoptosis in various malignant cell lines and is highly active against APL cells
      derived for As(2)O(3) resistance. We provide evidence that darinaparsin triggers
      apoptosis by inducing signaling pathways that do not completely overlap with
      As(2)O(3). We show that darinaparsin induces apoptosis and oxidative stress to a
      greater extent than As(2)O(3), although like As(2)O(3), darinaparsin-induced
      toxicity is c-Jun NH(2)-terminal kinase-dependent. However, darinaparsin does not
      induce promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR alpha)
      degradation or rearrange PML nuclear bodies in APL cells, nor is its toxicity
      increased by glutathione depletion. Darinaparsin treatment results in higher
      intracellular arsenic accumulation when compared to As(2)O(3) treatment. This may
      be explained by our finding that As(2)O(3), but not darinaparsin, is efficiently
      exported by ABCC1, suggesting increased therapeutic efficacy of darinaparsin in
      ABCC1-overexpressing tumors. Our studies indicate that darinaparsin efficiently
      kills tumor cells with increased antioxidant capacity and drug exporters and
      suggest that darinaparsin may have a broader therapeutic spectrum than As(2)O(3).

PMID- 18633431
TI  - Ex vivo priming of CD4 T cells converts immunological tolerance into effective
      antitumor immunity in a murine model of acute lymphoblastic leukemia.
AB  - Tumor escape mechanisms in leukemia are not well defined. To dissect
      immunological mechanisms responsible for immune tolerance toward leukemia, we
      established a murine model system allowing clonotypic analysis of leukemia
      specific CD4 T cells recognizing ovalbumin (OVA). Upon i.v. injection of
      genetically engineered leukemia cells, dendritic cells (DCs) engulfed, processed
      and presented OVA to OVA-specific CD4 T cells. Consequently, leukemia-specific T
      cells were primed in vivo as shown by expression of activation markers and
      proliferative responses. However, in spite of detectable CD4 T cell responses in
      vitro and in vivo, no effective anti-leukemia immunity was established. In
      contrast, adoptively transferred DO11.10 T cells that were primed ex vivo
      mediated effective antitumor immunity. Furthermore, ex vivo primed DO11.10 T
      cells showed high expression of Th1 cytokines (interferon-gamma, tumor necrosis
      factor-alpha and interleukin-2) whereas in vivo primed OVA-specific CD4 T cells
      showed incomplete differentiation (proliferation without cytokine production). We
      conclude that activated T cells lacking effector function develop through
      incomplete differentiation in leukemia-bearing mice. Thus, priming conditions of
      leukemia-specific CD4 T cells critically determines the balance between immunity
      or tolerance toward leukemia.

PMID- 18633432
TI  - High-resolution analysis of chromosome copy number alterations in
      angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified,
      with single nucleotide polymorphism-typing microarrays.
AB  - Angioimmunoblastic T-cell lymphoma (AILT) and peripheral T-cell lymphoma,
      unspecified (PTCL-u) are relatively frequent subtypes of T- or natural killer
      cell lymphoma. To characterize the structural anomalies of chromosomes associated
      with these disorders, we here determined chromosome copy number alterations
      (CNAs) and loss of heterozygosity (LOH) at >55,000 single nucleotide polymorphism
      loci for clinical specimens of AILT (n=40) or PTCL-u (n=33). Recurrent copy
      number gain common to both conditions was detected on chromosomes 8, 9 and 19,
      whereas common LOH was most frequent for a region of chromosome 2. AILT- or PTCL
      u-specific CNAs or LOH were also identified at 21 regions, some spanning only a
      few hundred base pairs. We also identified prognosis-related CNAs or LOH by
      several approaches, including Cox's proportional hazard analysis. Among the genes
      that mapped to such loci, a poor prognosis was linked to overexpression of CARMA1
      at 7p22 and of MYCBP2 at 13q22, with both genes being localized within regions of
      frequent copy number gain. For a frequent LOH region at 2q34, we also identified
      IKAROS family zinc-finger 2 cDNAs encoding truncated proteins. Our data indicate
      that AILT and PTCL-u consist of heterogeneous subgroups with distinct
      transforming genetic alterations.

PMID- 18633433
TI  - Doubling time of soluble CD23: a powerful prognostic factor for newly diagnosed
      and untreated stage A chronic lymphocytic leukemia patients.
AB  - Soluble CD23 (sCD23) levels correlate with the stage, prognosis and overall
      survival (OS) of patients with chronic lymphocytic leukemia (CLL). Therefore, we
      prospectively evaluated sCD23 doubling time (sCD23DT) as a prognostic factor for
      time to treatment (TTT) and OS in 56 newly diagnosed and untreated CLL patients
      at Binet stage A, and compared it to the most commonly used biological prognostic
      factors: lymphocyte doubling time, immunoglobulin variable heavy chain (IgVH)
      mutational status and zeta-associated protein-70 (ZAP-70), CD38, and lipoprotein
      lipase (LPL) expression. In patients with sCD23DT <1 year, the median TTT and OS
      were 20 and 83 months compared to 141 and 177 months in patients with sCD23DT >1
      year (P<0.0001). Among patients with poor prognostic factors (ZAP-70+, LPL+ and
      CD38+), an sCD23DT <1 year identified a subpopulation with a shorter TTT.
      Patients with unmutated IgVH and an sCD23DT <1 year had a median TTT and OS of 14
      and 83 months, respectively, whereas these values were 70 and >177 months when
      sCD23DT was >1 year (P<0.0001 and P=0.0219, respectively). Finally, in a Cox
      multivariate analysis, sCD23DT was the sole independent prognostic factor for TTT
      (P=0.0027). Furthermore, sCD23DT refines the prognosis given by other classical
      prognostic factors. These observations support the introduction of sCD23
      evaluation into the routine assessment of CLL patients.

PMID- 18633434
TI  - Murine neonatal melanocytes exhibit a heightened proliferative response to
      ultraviolet radiation and migrate to the epidermal basal layer.
AB  - Melanocytes respond to UVR not only by producing melanin, but also by
      proliferating. This is essentially a protective response. We have studied the
      melanocyte proliferative response after a single UVR exposure to neonatal mice.
      At 3 days post-UVR in wild-type neonates we observed a marked melanocyte
      activation not seen in adults. Melanocytes migrated to the epidermal basal layer,
      their numbers peaking at 3-5 days after UVR then diminishing. They appeared to
      emanate from the hair follicle, migrating to the epidermis via the outer root
      sheath. In melanoma-prone mice with melanocyte-specific overexpression of
      Hras(G12V), basal layer melanocytes were increased in size and dendricity
      compared to UVR-treated wild-type mice. Melanocytes in mice carrying a pRb
      pathway cell-cycle defect (oncogenic Cdk4(R24C)) did not show an enhanced
      response to UVR such as those carrying Hras(G12V). The exquisite sensitivity to
      UVR-induced proliferation and migration that characterizes neonatal mouse
      melanocytes may partly explain the utility of this form of exposure for inducing
      melanoma in mice that carry oncogenic mutations.

PMID- 18633435
TI  - Arsenite suppresses Notch1 signaling in human keratinocytes.
AB  - Arsenic is a well-known human skin carcinogen whose mechanism of action remains
      to be elucidated. In this work using cultured human epidermal cells, arsenite
      suppressed accumulation of the transcriptionally active intracellular domain of
      Notch1. The cells responded to an active peptide from the Notch1 ligand, Jagged1,
      with increased levels of differentiation marker mRNAs and decreased colony
      forming ability. Arsenite suppressed Jagged1 effects and expression of Jagged1
      mRNA as well. Moreover, exposure of the cells to a gamma-secretase inhibitor
      prevented Notch1 processing, decreased cell size and differentiation marker
      expression, and increased proliferative potential, all effects that occur with
      arsenite treatment. Thus, arsenite action in suppressing keratinocyte
      differentiation while maintaining germinative capability could be due to
      inhibition of Notch1 signaling subsequent to ligand binding. This work also
      revealed that such arsenite action depends upon epidermal growth factor receptor
      kinase activity. These findings may help to explain how arsenite, by decreasing
      generation of the tumor suppressor Notch1, contributes to skin carcinogenesis.

PMID- 18633436
TI  - Matrix metalloproteinase-21 expression is associated with keratinocyte
      differentiation and upregulated by retinoic acid in HaCaT cells.
AB  - In the skin, expression of several matrix metalloproteinases (MMPs) occurs in
      response to tissue injury, tumorigenesis, angiogenesis, apoptosis, and
      inflammation. The recently cloned MMP-21 has been implicated in skin development
      and various epithelial cancers. In this study, we found that it is also expressed
      by differentiated keratinocytes (KCs) in various benign skin disorders, in which
      it was not associated with KC apoptosis or proliferation, and in organotypic
      cultures. Furthermore, MMP-21 was induced in keratinocytes in association with
      increased calcium and presence of the differentiation marker filaggrin. In stably
      transfected A431 and HEK293 cell lines, MMP-21 increased invasion of cells but
      did not associate with increased apoptosis, proliferation, or epithelial-to
      mesenchymal transition. Of various agents tested in HaCaT cell cultures, only
      retinoic acid (10(-6) M) and staurosporine (2.5 x 10(-8) M) upregulated MMP-21
      mRNA and protein expression, whereas tumor promoters, hormones, or dexamethasone
      were without effect. Our results suggest that MMP-21 may be an important protease
      in the terminal differentiation of keratinocytes.

PMID- 18633437
TI  - Dominance of nonmalignant T-cell clones and distortion of the TCR repertoire in
      the peripheral blood of patients with cutaneous CD30+ lymphoproliferative
      disorders.
AB  - The CD30-positive cutaneous lymphoproliferative disorders (CLPD) include
      lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large T-cell
      lymphoma (cALCL). Despite the malign-appearing histology, an excellent prognosis
      and spontaneous regression of single lesions characterize LyP. Even after years
      of clinical remission newly erupting lesions often harbor a T-cell clone
      identical to the initial one. This fact raises the question whether the clonal T
      cell population persists in the peripheral blood. Therefore we investigated
      genomic DNA of 126 samples of lesional skin and peripheral blood from 31 patients
      with CLPD, obtained during both active disease and clinical remission. We
      performed molecular genetic analysis by combining T-cell receptor (TCR)-gamma PCR
      with the GeneScan technique and assessed the TCR repertoire in selected blood
      samples by beta-variable complementarity-determining region 3 (CDR3)
      spectratyping qualitatively and quantitatively. We were able to detect a clonal T
      cell population in 36/43 (84%) skin samples and in 35/83 (42%) blood samples.
      Comparison of the compartments in each patient demonstrated different T-cell
      clones in skin and blood, suggesting a reactive nature of the clonal T cells in
      the blood. Moreover, CDR3 spectratyping revealed a restricted T-cell repertoire
      in the blood, suggesting T-cell stimulation by an unknown antigen.

PMID- 18633438
TI  - Genotypic and gene expression studies in congenital melanocytic nevi: insight
      into initial steps of melanotumorigenesis.
AB  - Large congenital melanocytic nevi (CMNs) are said to have a higher propensity to
      malignant transformation compared with acquired nevi. Thus, they represent a good
      model for studying initial steps of melanotumorigenesis. We have performed
      genotypic (karyotype, fluorescence in situ hybridization, and mutational
      analyses) and differential expression studies on a large cohort of medium (n=3)
      and large (n=24) CMN. Chromosomal abnormalities were rare and single, a feature
      probably reflecting the benignity of these lesions. Mutational screening showed a
      high frequency of NRAS mutations in our series (19/27 cases, 70%), whereas BRAF
      mutations were less common (4/27 cases, 15%). Differential did not show
      significant alterations of cellular processes such as cell proliferation, cell
      migration/invasion, angiogenesis, apoptosis, and immune/inflammatory responses.
      However, significant downregulation of genes involved in pigmentation and
      upregulation of genes playing a role in DNA protection were observed. Lastly, our
      microarrays displayed upregulation of genes mediating chemoresistance in cancer.
      As alteration of pigmentation mechanisms can trigger oxidative damage, increased
      expression of genes involved in maintenance of DNA integrity might reflect the
      ability of nevocytic cells to self-protect against cellular stress. Furthermore,
      the observed alterations linked to chemoresistance might partially account for
      the well-known inefficacy of chemotherapy in malignant melanoma.

PMID- 18633439
TI  - IKKalpha is a p63 transcriptional target involved in the pathogenesis of
      ectodermal dysplasias.
AB  - The transcription factor p63 plays a pivotal role in the development and
      differentiation of the epidermis and epithelial appendages. Indeed, mutations in
      p63 are associated with a group of ectodermal dysplasias characterized by skin,
      limb, and craniofacial defects. It was hypothesized that p63 exerts its functions
      by activating specific genes during epidermal development, which in turn regulate
      epidermal stratification and differentiation. We have identified I-kappaB kinase
      alpha (IKKalpha) as a direct transcriptional target of p63 that is induced at
      early phases of terminal differentiation of primary keratinocytes. We show that
      the DeltaNp63 isoform is required for IKKalpha expression in differentiating
      keratinocytes and that mutant p63 proteins expressed in ectodermal dysplasia
      patients exhibit defects in inducing IKKalpha. Furthermore, we observed reduced
      IKKalpha expression in the epidermis of an ankyloblepharon ectodermal dysplasia
      clefting patient. Our data demonstrate that a failure to properly express
      IKKalpha may play a role in the development of ectodermal dysplasias.

PMID- 18633440
TI  - Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re
      epithelialization during cutaneous wound healing.
AB  - The wound microenvironment comprises constituents, such as the extracellular
      matrix (ECM), that regulate with temporal and spatial precision, the migratory,
      proliferative, and contractility of wound cells. Prompt closure of the wound is
      an early and critical phase of healing and beta1 integrins are important in this
      process. We previously reported a marked increase in integrin alpha9beta1
      expression in epidermal keratinocytes in cutaneous and corneal wounds. However,
      the functional role of keratinocyte alpha9beta1 during re-epithelialization is
      unknown and analysis has been precluded by the lethal phenotype of integrin
      alpha9beta1 knockout mice. We now report that in conditional integrin alpha9
      knockout (K14-alpha9 null) mice, normal proliferation occurs in epidermal
      keratinocytes and corneal basal cells. Normal epidermal keratinocyte morphology
      is also retained. However, corneal basal cell morphology and epithelial thickness
      are altered, suggesting that loss of integrin alpha9beta1 results in abnormal
      corneal differentiation. In cutaneous wounds, the number of proliferating
      epidermal keratinocytes is significantly reduced in K14-alpha9 null mice compared
      with alpha9(fl/-) mice, but not in Cre (control) mice. The decreased keratinocyte
      proliferation observed in K14-alpha9 null mice negatively impacts healing,
      resulting in a thinner migrating epithelium, demonstrating that alpha9beta1 is
      crucial for efficient and proper re-epithelialization during cutaneous wound
      healing.

PMID- 18633441
TI  - MC polyomavirus is frequently present in Merkel cell carcinoma of European
      patients.

PMID- 18633442
TI  - Poly(ADP-ribose) polymerase mediates inflammation in a mouse model of contact
      hypersensitivity.

PMID- 18633444
TI  - In vivo reflectance confocal microscopy enhances secondary evaluation of
      melanocytic lesions.
AB  - We recently described an in vivo reflectance confocal microscopy (RCM) method and
      our aim was to evaluate a possible additive value of this type of analysis in the
      management of melanocytic lesions. In two referral centers (Sydney and Modena),
      lesions (203 nevi and 123 melanomas (MMs) with a median Breslow thickness of 0.54
      mm) were excised on the basis of clinical suspicion (history, dermoscopy
      examination, and/or digital monitoring). The RCM method was also trialed on a non
      biopsied population of 100 lesions, which were clinically and dermoscopically
      diagnosed as benign nevi. All RCM and dermoscopy diagnoses were performed blinded
      to the histopathological diagnosis. Firstly, in the study population, a high
      interobserver agreement (on a subset of 90 lesions) was seen with the RCM method,
      which had superior specificity (68%, 95% confidence interval (95% CI): 61.1-74.3)
      for the diagnosis of MM compared with dermoscopy (32%, 95% CI: 25.9-38.7), while
      showing no difference in sensitivity (91%, 95% CI: 84.6-95.5, RCM; 88%, 95% CI:
      80.7-92.6 dermoscopy). The two techniques had a weak correlation, resulting in
      only 2.4% of MMs being misclassified by both techniques. Diagnosis of light
      colored lesions is improved by RCM (specificity 84%, 95% CI: 66.3-94.5) compared
      with dermoscopy (specificity 39%, 95% CI: 23.7-56.2). Secondly, the RCM method
      classified 100% of the non-biopsied control nevi population as benign.

PMID- 18633443
TI  - Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell
      polarizing myeloid dendritic cells.
AB  - Myeloid dermal dendritic cells (DCs) accumulate in chronically inflamed tissues
      such as psoriasis. The importance of these cells for psoriasis pathogenesis is
      suggested by comparative T-cell and DC-cell counts, where DCs outnumber T cells.
      We have previously identified CD11c(+)-blood dendritic cell antigen (BDCA)-1(+)
      cells as the main resident dermal DC population found in normal skin. We now show
      that psoriatic lesional skin has two populations of dermal DCs: (1) CD11c(+)BDCA
      1(+) cells, which are phenotypically similar to those contained in normal skin
      and (2) CD11c(+)BDCA-1(-) cells, which are phenotypically immature and produce
      inflammatory cytokines. Although BDCA-1(+) DCs are not increased in number in
      psoriatic lesional skin compared with normal skin, BDCA-1(-) DCs are increased 30
      fold. For functional studies, we FACS-sorted psoriatic dermal single-cell
      suspensions to isolate these two cutaneous DC populations, and cultured them as
      stimulators in an allogeneic mixed leukocyte reaction. Both BDCA-1(+) and BDCA-1(
      ) myeloid dermal DC populations induced T-cell proliferation, and polarized T
      cells to become T helper 1 (Th1) and T helper 17 (Th17) cells. In addition,
      psoriatic dermal DCs induced a population of activated T cells that
      simultaneously produced IL-17 and IFN-gamma, which was not induced by normal skin
      dermal DCs. As psoriasis is believed to be a mixed Th17/Th1 disease, it is
      possible that induction of these IL-17(+)IFN-gamma(+) cells is pathogenic. These
      cytokines, the T cells that produce them, and the inducing inflammatory DCs may
      all be important new therapeutic targets in psoriasis.

PMID- 18633445
TI  - Ex vivo-transduced autologous skin fibroblasts expressing human Lim
      mineralization protein-3 efficiently form new bone in animal models.
AB  - Local gene transfer of the human Lim mineralization protein (LMP), a novel
      intracellular positive regulator of the osteoblast differentiation program, can
      induce efficient bone formation in rodents. To develop a clinically relevant gene
      therapy approach to facilitate bone healing, we have used primary dermal
      fibroblasts transduced ex vivo with Ad.LMP-3 and seeded on a
      hydroxyapatite/collagen matrix prior to autologous implantation. Here, we
      demonstrate that genetically modified autologous dermal fibroblasts expressing
      Ad.LMP-3 are able to induce ectopic bone formation following implantation of the
      matrix into mouse triceps and paravertebral muscles. Moreover, implantation of
      the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size
      defect model results in efficient healing, as determined by X-rays, histology and
      three-dimensional microcomputed tomography (3DmuCT). These results demonstrate
      the effectiveness of the non-secreted intracellular osteogenic factor LMP-3 in
      inducing bone formation in vivo. Moreover, the utilization of autologous dermal
      fibroblasts implanted on a biomaterial represents a promising approach for
      possible future clinical applications aimed at inducing new bone formation.

PMID- 18633446
TI  - Novel anti-VEGF chimeric molecules delivered by AAV vectors for inhibition of
      retinal neovascularization.
AB  - Vascular endothelial growth factor (VEGF) is important in pathological
      neovascularization, which is a key component of diseases such as the wet form of
      age-related macular degeneration, proliferative diabetic retinopathy and cancer.
      One of the most potent naturally occurring VEGF binders is VEGF receptor Flt-1.
      We have generated two novel chimeric VEGF-binding molecules, sFLT01 and sFLT02,
      which consist of the second immunoglobulin (IgG)-like domain of Flt-1 fused
      either to a human IgG1 Fc or solely to the CH3 domain of IgG1 Fc through a
      polyglycine linker 9Gly. In vitro analysis showed that these novel molecules are
      high-affinity VEGF binders. We have demonstrated that adeno-associated virus
      serotype 2 (AAV2)-mediated intravitreal gene delivery of sFLT01 efficiently
      inhibits angiogenesis in the mouse oxygen-induced retinopathy model. There were
      no histological observations of toxicity upon persistent ocular expression of
      sFLT01 for up to 12 months following intravitreal AAV2-based delivery in the
      rodent eye. Our data suggest that AAV2-mediated intravitreal gene delivery of our
      novel molecules may be a safe and effective treatment for retinal
      neovascularization.

PMID- 18633447
TI  - Persistent episomal transgene expression in liver following delivery of a
      scaffold/matrix attachment region containing non-viral vector.
AB  - An ideal gene therapy vector should enable persistent transgene expression
      without limitations of safety and reproducibility. Here we report the development
      of a non-viral episomal plasmid DNA (pDNA) vector that appears to fulfil these
      criteria. This pDNA vector combines a scaffold/matrix attachment region (S/MAR)
      with a human liver-specific promoter (alpha1-antitrypsin (AAT)) in such a way
      that long-term expression is enabled in murine liver following hydrodynamic
      injection. Long-term expression is demonstrated by monitoring the longitudinal
      luciferase expression profile for up to 6 months by means of in situ
      bioluminescent imaging. All relevant control pDNA constructs expressing
      luciferase are unable to sustain significant transgene expression beyond 1 week
      post-administration. We establish that this shutdown of expression is due to
      promoter methylation. In contrast, the S/MAR element appears to inhibit
      methylation of the AAT promoter thereby preventing transgene silencing. Although
      this vector appears to be maintained as an episome throughout, we have no
      evidence for its establishment as a replicating entity. We conclude that the
      combination of a mammalian, tissue-specific promoter with the S/MAR element is
      sufficient to drive long-term episomal pDNA expression of genes in vivo.

PMID- 18633449
TI  - Quorum sensing in Cyanobacteria: N-octanoyl-homoserine lactone release and
      response, by the epilithic colonial cyanobacterium Gloeothece PCC6909.
AB  - Quorum sensing involving acyl homoserine lactones (AHLs) is a density-dependent
      form of intercellular communication that occurs in many different members of the
      group Proteobacteria. However, to date, there have been few investigations of its
      occurrence in cyanobacteria. Here, using both a bioreporter Agrobacterium
      tumefaciens NTL4 (PZLR4) and mass spectrometry, we provide evidence of N-octanoyl
      homoserine lactone (C8-AHL) production in axenic cultures of the cyanobacterium
      Gloeothece PCC6909 and its sheathless mutant PCC6909/1. Accumulation of C8-AHL in
      the culture medium of laboratory cultures of Gloeothece followed a pattern
      characteristic of the phenomenon of autoinduction, a common feature of functional
      AHL-based quorum-sensing systems. Analysis by two-dimensional gel electrophoresis
      showed that, in response to treatment with C8-AHL, early growth-stage cells of
      PCC6909/1 showed changes in expression of 43 proteins compared with untreated
      cells. Among the 15 proteins that showed more than a twofold change in expression
      were RuBisCo, glutamate synthase, chorismate synthase, a member of the LysR
      family of transcriptional regulators (all upregulated), and enolase and aldolase,
      both of which were downregulated. The significance of such changes in response to
      C8-AHL is discussed in relation to carbohydrate and amino-acid metabolism and
      involvement of Gloeothece in biofilms.

PMID- 18633448
TI  - Treatment of avascular necrosis of the femoral head by hepatocyte growth factor
      transgenic bone marrow stromal stem cells.
AB  - The treatment of hormone-induced early-stage avascular necrosis of the femoral
      head (ANFH) with transplantation of hepatocyte growth factor (HGF)-transgenic
      bone marrow stromal stem cells (BMSCs) was examined. A rabbit model of hormone
      induced early ANFH was first established. BMSCs were transplanted by core
      decompression under the guidance of computed tomography (CT). A supportive
      fibrinogen drug delivery mixture (FG) was tested for mechanical enhancement of
      stem cell delivery. Therapeutic efficacy was evaluated by CT, magnetic resonance
      imaging (MRI), CT perfusion imaging, ink artery infusion angiography, hematoxylin
      and-eosin staining and immunohistochemical staining for extracellular signal
      regulated kinase-1/2 of pathological sections. A regular arrangement of
      trabeculae and obvious bone regeneration were observed in the animals receiving
      transplanted transgenic BMSCs with FG. Newly generated capillaries were visible
      on the bone plates of the trabeculae, and the bone marrow was rich in
      hematopoietic tissue. These results demonstrate that the combination of core
      decompression and transplantation of HGF transgenic autologous BMSCs enhanced
      blood vessel regeneration and bone reconstruction in the ANFH model. This study
      provides experimental data that motivate possible clinical use of this
      therapeutic strategy.

PMID- 18633451
TI  - Probing feature selectivity of neurons in primary visual cortex with natural
      stimuli.
AB  - One way to characterize neural feature selectivity is to model the response
      probability as a nonlinear function of the output of a set of linear filters
      applied to incoming signals. Traditionally these linear filters are measured by
      probing neurons with correlated Gaussian noise ensembles and calculating
      correlation functions between incoming signals and neural responses. It is also
      important to derive these filters in response to natural stimuli, which have been
      shown to have strongly non-Gaussian spatiotemporal correlations. An information
      theoretic method has been proposed recently for reconstructing neural filters
      using natural stimuli in which one looks for filters whose convolution with the
      stimulus ensemble accounts for the maximal possible part of the overall
      information carried the sequence of neural responses. Here we give a first-time
      demonstration of this method on real neural data, and compare responses of
      neurons in cat primary visual cortex driven with natural stimuli, noise
      ensembles, and moving gratings. We show that the information-theoretic method
      achieves the same quality of filter reconstruction for natural stimuli as that of
      well-established white-noise methods. Major parameters of neural filters derived
      from noise ensembles and natural stimuli, as well as from moving gratings are
      consistent with one another. We find that application of the reverse correlation
      method to natural stimuli ensembles leads to significant distortions in filters
      for a majority of studied cells with non-zero reverse-correlation filter.

PMID- 18633450
TI  - Surface expression of Bcl-2 in chronic lymphocytic leukemia and other B-cell
      leukemias and lymphomas without a breakpoint t(14;18).
AB  - Since its discovery in follicular lymphoma cells at the breakpoint t(14;18), Bcl
      2 has been studied extensively in many basic and clinical science settings. Bcl-2
      can locate as an integral mitochondrial membrane component, where its primary
      role is to block apoptosis by maintaining membrane integrity. Here we show that
      Bcl-2 also can position on the outer cell surface membrane of B cells from
      patients with chronic lymphocytic leukemia (B-CLL) and certain other leukemias
      that do not classically possess the chromosomal breakpoint t(14;18). Although low
      levels of Bcl-2 can be detected on the surface membrane of apparently healthy
      leukemic and normal B cells, expression of Bcl-2 correlates best with spontaneous
      or induced apoptosis. Notably, upon induction of apoptosis, B-CLL cells were much
      more efficient in upregulating surface Bcl-2 than normal B cells. It is not clear
      if this surface membrane expression is a passive consequence of the apoptotic
      process or an active attempt by the B cell to abort cell death by stabilizing the
      plasma membrane.

PMID- 18633452
TI  - CURRENT STATUS AND RIGHT-CENSORED DATA STRUCTURES WHEN OBSERVING A MARKER AT THE
      CENSORING TIME.
AB  - We study nonparametric estimation with two types of data structures. In the first
      data structure n i.i.d. copies of (C, N(C)) are observed, where N is a finite
      state counting process jumping at time-variables of interest and C a random
      monitoring time. In the second data structure n i.i.d. copies of (C ? T, I (T <=
      C), N(C ? T)) are observed, where N is a counting process with a final jump at
      time T (e.g., death). This data structure includes observing right-censored data
      on T and a marker variable at the censoring time.In these data structures, easy
      to compute estimators, namely (weighted)-pool-adjacent-violator estimators for
      the marginal distributions of the unobservable time variables, and the Kaplan
      Meier estimator for the time T till the final observable event, are available.
      These estimators ignore seemingly important information in the data. In this
      paper we prove that, at many continuous data generating distributions the ad hoc
      estimators yield asymptotically efficient estimators of [Formula: see text]
      estimable parameters.

PMID- 18633453
TI  - On Using Truncated Sequential Probability Ratio Test Boundaries for Monte Carlo
      Implementation of Hypothesis Tests.
AB  - When designing programs or software for the implementation of Monte Carlo (MC)
      hypothesis tests, we can save computation time by using sequential stopping
      boundaries. Such boundaries imply stopping resampling after relatively few
      replications if the early replications indicate a very large or very small p
      value. We study a truncated sequential probability ratio test (SPRT) boundary and
      provide a tractable algorithm to implement it. We review two properties desired
      of any MC p-value, the validity of the p-value and a small resampling risk, where
      resampling risk is the probability that the accept/reject decision will be
      different than the decision from complete enumeration. We show how the algorithm
      can be used to calculate a valid p-value and confidence intervals for any
      truncated SPRT boundary. We show that a class of SPRT boundaries is minimax with
      respect to resampling risk and recommend a truncated version of boundaries in
      that class by comparing their resampling risk (RR) to the RR of fixed boundaries
      with the same maximum resample size. We study the lack of validity of some simple
      estimators of p-values and offer a new simple valid p-value for the recommended
      truncated SPRT boundary. We explore the use of these methods in a practical
      example and provide the MChtest R package to perform the methods.

PMID- 18633454
TI  - Proteomics studies of pancreatic cancer.
AB  - Pancreatic cancer is the fourth leading cause of cancer death in the United
      States, with 4% survival 5 years after diagnosis. Biomarkers are desperately
      needed to improve earlier, more curable cancer diagnosis and to develop new
      effective therapeutic targets. The development of quantitative proteomics
      technologies in recent years offers great promise for understanding the complex
      molecular events of tumorigenesis at the protein level, and has stimulated great
      interest in applying the technology for pancreatic cancer studies. Proteomic
      studies of pancreatic tissues, juice, serum/plasma, and cell lines have recently
      attempted to identify differentially expressed proteins in pancreatic cancer to
      dissect the abnormal signaling pathways underlying oncogenesis, and to detect new
      biomarkers. It can be expected that the continuing evolution of proteomics
      technology with better resolution and sensitivity will greatly enhance our
      capability in combating pancreatic cancer.

PMID- 18633455
TI  - Synthetic Studies in Phytochrome Chemistry.
AB  - An account is given of the author's several approaches to the synthesis of the
      parent chromophore of phytochrome (1), a protein-bound linear tetrapyrrole
      derivative that controls photomorphogenesis in higher plants. These studies
      culminated in enantioselective syntheses of both 2R- and 2S-phytochromobilin (4),
      as well as several (13)C-labeled derivatives designed to probe the site of Z,E
      isomerization during photoexcitation. When reacted in vitro, synthetic 2R-4 and
      recombinant-derived phytochrome apoprotein N-C produced a protein-bound
      chromophore with identical difference spectra to naturally occurring 1.

PMID- 18633456
TI  - In vivo quantitative microvasculature phenotype imaging of healthy and malignant
      tissues using a fiber-optic confocal laser microprobe.
AB  - Real-time in vivo imaging of the microvasculature may help both earlier clinical
      detection of disease and the understanding of tumor-host interaction at various
      stages of progression. In vivo confocal and multiphoton microscopy is often
      hampered by bulky optics setup and has limited access to internal organs. A fiber
      optic setup avoids these limitations and offers great user maneuverability. We
      report here the in vivo validation of a fiber-optic confocal fluorescence
      microprobe imaging system. In addition, we developed an automated fractal-based
      image analysis to characterize microvascular morphology based on vessel diameter
      distribution, density, volume fraction, and fractal dimension from real-time
      data. The system is optimized for use in the far-red and near-infrared region.
      The flexible 1.5-mm-diameter fiber-optic bundle and microprobe enable great user
      maneuverability, with a field of view of 423 x 423 microm and a tissue
      penetration of up to 15 microm. Lateral and axial resolutions are 3.5 and 15
      microm. We show that it is possible to obtain high temporal and spatial
      resolution images of virtually any abdominal viscera in situ using a far-red
      blood pool imaging probe. Using an orthotopic model of pancreatic ductal
      adenocarcinoma, we characterized the tumor surface capillary and demonstrated
      that the imaging system and analysis can quantitatively differentiate between the
      normal and tumor surface capillary. This clinically approved fiber-optic system,
      together with the fractal-based image analysis, can potentially be applied to
      characterize other tumors in vivo and may be a valuable tool to facilitate their
      clinical evaluation.

PMID- 18633457
TI  - Expression of GSDML Associates with Tumor Progression in Uterine Cervix Cancer.
AB  - Gasdermin-like (GSDML) belongs to the gasdermin-domain-containing protein family
      (GSDMDC family) that is involved in carcinogenesis and hearing impairment.
      However, the role of GSDML in carcinogenesis remains unclear. In this study, we
      identified four isoforms of GSDML gene. The primary and longest isoform GSDML1 is
      widely expressed in human cancer cell lines. GFP-GSDML1 fusion protein was
      localized predominantly in the nucleus of human breast cancer MCF7 and cervical
      cancer HeLa cells but exclusively in the cytoplasm of hepatocellular carcinoma
      HepG2 cells. Importantly, immunohistochemistry analysis showed that the GSDML
      protein in the nuclei is expressed at a higher level in uterine cervix cancer
      tissues than in the adjacent cancer tissues and corresponding nonneoplastic
      tissues. Such significance was not observed in hepatocellular carcinoma tissues.
      Ectopic expression of GSDML1 enhanced the growth of cultured cells, whereas
      inhibition of its endogenous expression decreased proliferation. Furthermore,
      GSDML1 had significant effects on promoting bromodeoxyuridine incorporation in
      cells. However, GSDML1 could neither promote malignant transformation nor gain
      the ability of colony formation or carcinogenicity on nude mice. Collectively,
      these results suggest that GSDML can promote cell proliferation, and it might be
      correlated with carcinogenesis and progression of uterine cervix cancer.

PMID- 18633458
TI  - Tomoregulin internalization confers selective cytotoxicity of immunotoxins on
      prostate cancer cells.
AB  - We have recently identified and validated the prostate cancer antigen Tomoregulin
      as a target for the radioimmunotherapy for prostate cancer. Here, we provide
      evidence that Tomoregulin is an internalizing antigen and a potential target for
      immunotoxins. First, the cell surface localization of Tomoregulin was confirmed
      by flow cytometry, and its expression levels were determined by whole-cell
      binding assays. Second, laser scanning confocal microscopy revealed Tomoregulin
      internalization into the cytoplasm on antibody binding at 37 degrees C. The
      internalized Tomoregulin was found to colocalize with acidic vesicles. Third,
      internalization kinetics assays using (125)I-labeled anti-Tomoregulin mouse
      monoclonal antibody 2H8 demonstrated that the amount of internalized antigen
      antibody complexes increased with time and reached approximately 25% of the total
      surface antigen after 60 to 90 minutes. Because 2H8 is capable of binding to
      Tomoregulin on the cell surface and can be internalized, we finally evaluated 2H8
      as a means of targeting toxic payloads to prostate cancer cells. 2H8 was coupled
      to the cytotoxin saporin through a secondary antibody (Mab-ZAP) in indirect
      immunotoxin assays. Cell killing occurred on Tomoregulin-positive cells (Clone69)
      at the immunotoxin concentrations not affecting the Tomoregulin-negative cells
      (PC-3). In contrast to 2H8, the control antibody (mouse anti-c-Myc antibody 9E10)
      had no effect on cells in the presence of Mab-ZAP. Thus, Tomoregulin
      internalization confers selective cytotoxicity of immunotoxins on prostate cancer
      cells, and Tomoregulin-mediated delivery of immunotoxin has potential as a
      prostate cancer therapy.

PMID- 18633459
TI  - Molecular characterization of synovial sarcoma in children and adolescents:
      evidence of akt activation.
AB  - Synovial sarcoma (SS) is the most frequent nonrhabdomyosarcomatous soft tissue
      sarcoma encountered in adolescents and young adults, and despite advances in the
      treatment of local disease, metastases remain the main cause of death. The aim of
      this study was to characterize a single-center series of pediatric SS molecularly
      to seek any biomarkers or pathways that might make suitable targets for new
      agents. Seventeen cases of pediatric SS showing the SYT-SSX fusion transcript
      were screened immunohistochemically, biochemically, molecularly, and
      cytogenetically (depending on the available material) to investigate any
      expression/activation of epidermal growth factor receptor, platelet-derived
      growth factor receptor alpha (PDGFRalpha), PDGFRbeta, Akt, and deregulated Wnt
      pathway. The most relevant outcome was the finding of activated epidermal growth
      factor receptor, PDGFRalpha, and PDGFRbeta, which activated Akt in both the
      monophasic and biphasic histologic subtypes. Consistently, Akt activation was
      completely abolished in an SS cell line assay when stimulated by PDGF-AA and
      treated with the phosphatidylinositol 3-kinase inhibitor LY294002. Our results
      also showed the nuclear localization of beta-catenin and cyclin D1 gene products
      in monophasic SS and the movement of beta-catenin into the cytoplasm in the
      glandular component of the biphasic subtype. Although they need to be confirmed
      in larger series, these preliminary data suggest that therapeutic strategies
      including specific inhibitors of the phosphatidylinositol 3-kinase/Akt pathway
      might be exploited in SS.

PMID- 18633460
TI  - CHFR: A Novel Mitotic Checkpoint Protein and Regulator of Tumorigenesis.
AB  - Checkpoint with FHA and RING finger domains (CHFR) was first recognized as an
      early mitotic checkpoint protein that delayed the cell cycle in response to
      microtubule-targeting drugs. It is an E3 ubiquitin ligase that ubiquitinates
      target proteins to direct them to the proteasome for degradation or to alter
      their activity. To date, however, the downstream target proteins critical to
      CHFR's normal cellular functions largely remain unidentified with the exception
      of the key mitosis regulators, and oncogenes, PLK1 and Aurora A kinases. Rapidly
      growing evidence in mice, primary human tumors, and mammalian cell culture models
      indicate that CHFR may also function as a potent tumor suppressor. Interestingly,
      studies reported to date suggest that CHFR both controls a novel prophase
      checkpoint early in mitosis and regulates chromosome segregation later in mitosis
      to maintain genomic stability. In addition, loss of CHFR sensitizes cancer cells
      to microtubule poisons, altering chemoresponsiveness to taxanes and making it a
      potential biomarker for chemotherapeutic response. Importantly, CHFR may be one
      of the few proteins that are required for regulating the cell cycle and
      maintaining genomic instability to inhibit tumorigenesis.

PMID- 18633461
TI  - Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating
      Factor, GcMAF.
AB  - Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the
      principal macrophage-activating factor (MAF). The MAF precursor activity of serum
      Gc protein of prostate cancer patients was lost or reduced because Gc protein was
      deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from
      cancerous cells. Therefore, macrophages of prostate cancer patients having
      deglycosylated Gc protein cannot be activated, leading to immunosuppression.
      Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and
      sialidase generated the most potent MAF (termed GcMAF) ever discovered, which
      produces no adverse effect in humans. Macrophages activated by GcMAF develop a
      considerable variation of receptors that recognize the abnormality in malignant
      cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer
      patients received weekly administration of 100 ng of GcMAF. As the MAF precursor
      activity increased, their serum Nagalase activity decreased. Because serum
      Nagalase activity is proportional to tumor burden, the entire time course
      analysis for GcMAF therapy was monitored by measuring the serum Nagalase
      activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16
      patients had very low serum Nagalase levels equivalent to those of healthy
      control values, indicating that these patients are tumor-free. No recurrence
      occurred for 7 years.

PMID- 18633463
TI  - A clinical evaluation of extrinsic stain removal: a rotation-oscillation power
      toothbrush versus a dental prophylaxis.
AB  - AIM: To assess extrinsic stain removal efficacy of a power toothbrush and a
      dental prophylaxis followed by the use of a standardized American Dental
      Association (ADA) reference manual toothbrush. METHODS AND MATERIALS: This was a
      randomized, positive-controlled, examiner-blind, parallel group, two-week study.
      A Lobene stain examination was performed at baseline. Subjects were randomized to
      one of two treatment groups: Group 1: Oral-B Vitality Pro White power toothbrush
      or Group 2: Subjects receiving a dental prophylaxis then using a standardized ADA
      reference manual toothbrush. Subjects were instructed to brush their teeth with
      the assigned toothbrush and a fluoride dentifrice in front of a mirror twice per
      day for 2 minutes. Stain was reassessed following 2 weeks of brushing. RESULTS: A
      significant reduction (p <0.001) in mean Lobene composite scores after 2 weeks
      was found for Group 1 (90.6%) and Group 2 (94.4%). Both groups also showed a
      significant reduction (p <0.001) in extent and intensity scores. There was no
      significant group difference in reduction in mean Lobene composite scores
      (p>0.1). CONCLUSIONS: The Oral-B Vitality Pro White power toothbrush showed
      effective stain removal at a level similar to receiving an oral prophylaxis
      followed by the use of an ADA reference manual toothbrush. CLINICAL SIGNIFICANCE:
      In this small study the Oral-B Vitality Pro White power toothbrush achieved
      statistically significant stain removal between dental visits.

PMID- 18633462
TI  - Psychoneuroimmunology examined: The role of subjective stress.

PMID- 18633464
TI  - Alterations in HbA1c following minimal or enhanced non-surgical, non-antibiotic
      treatment of gingivitis or mild periodontitis in type 2 diabetic patients: a
      pilot trial.
AB  - AIM: The purpose of this pilot study was to determine and compare the effects of
      two protocols aimed at reducing periodontal inflammation, upon the metabolic
      control of the diabetic condition in subjects with elevated baseline glycosylated
      hemoglobin (HbA1c). METHODS AND MATERIALS: Forty-two non-smoking type 2 diabetes
      subjects with mildly elevated HbA1c (>7 but < 9%) and severely elevated (>9%)
      were randomized to one of two non-surgical periodontal therapy protocols.
      Patients in the "minimal therapy" (MT) group received scaling, root planning, and
      oral hygiene instructions on two occasions six months apart. Participants
      randomized to the "frequent therapy" (FT) protocol received scaling, root
      planing, and oral hygiene instructions at two-month intervals and were provided a
      0.12% chlorhexidine rinse for home use twice daily. Neither systemic nor local
      antibiotics were provided to either group. Subjects were asked to report any
      changes in diabetic medications, nutrition, and physical activity. Data analyses
      (ANOVA, t-test, Mann-Whitney) grouped subjects according to baseline HbA1c (>7
      and < 9%, or > 9%), treatment protocol (minimal or frequent), and +/- medication
      change. RESULTS: In both MT and FT groups the clinical attachment level (CAL)
      remained unchanged but the other measures [gingival index (GI) and pocket dept
      (PD)] of periodontal health improved. Mean reductions in plaque showed
      improvement but calculus was worse in the FT group, likely due to the use of
      chlorhexidine. At six months, the largest reduction of HbA1c was 3.7; experienced
      by a subject receiving FT but no changes in diabetic medication. Among the MT and
      no medication change subjects, the maximum reduction was 1.6. Overall mean
      reduction in HbA1c of 27 subjects with baseline HbA1c >9.0 and no medication
      change was 0.6 with no statistical difference between the MT and FT groups. Among
      the medication-change subjects with baseline HbA1c >9.0, mean reduction of 1.38
      was seen with FT compared to 1.10 with MT. CONCLUSION: Overall, modest
      improvements in HbA1c were detected with a trend towards FT being better than MT.
      Although this pilot trial was under-powered to detect small between-group
      differences, the magnitude of our findings (0.6 mean improvement in HbA1c)
      matches closely findings from the only meta-analysis conducted on this topic to
      date. Larger scale studies must be undertaken on diabetic patients with
      periodontal problems. CLINICAL SIGNIFICANCE: Preventive periodontal regimens for
      diabetic patients should be sufficiently intense and sustained to eliminate
      periodontal inflammation and should be closely coordinated with the patient's
      overall clinical diabetic management.

PMID- 18633465
TI  - The effect of in-office in combination with intracoronal bleaching on enamel and
      dentin bond strength and dentin morphology.
AB  - AIM: The aim of this study was to evaluate in vitro effects of the combination of
      in-office and intracoronal bleaching on enamel and dentin bond strength and on
      dentin morphology. METHODS AND MATERIALS: Bleaching treatment was performed on
      128 bovine teeth for three weeks. Intracoronal bleaching was performed in groups
      G1 to G3, and in the other groups a combination of in-office and intracoronal
      bleaching was performed. The following agents and materials were used (n=16): G1-
      sodium perborate and water (SP); G2- 37% carbamide peroxide (CP); G3- 35%
      hydrogen peroxide (HP); G4- HP + cotton pellet soaked in water (CPW); G5- HP +
      SP; G6- HP + CP; G7- HP + HP; and G8- CPW (control). Seven days after bleaching
      treatment the teeth were sectioned into two halves. One half of each tooth was
      ground to obtain a flat dentin surface. Dentin and enamel fragments were treated
      with a dentin/enamel resin adhesive. Resin composite was inserted in two
      increments and polymerized for 20 seconds. Following the restorative procedures,
      specimens were sectioned into beams with a rectangular cross-sectional area of
      approximately 1 mm2. Microtensile testing was performed in a universal testing
      machine. Bond strengths (in MPa) were calculated and the data were submitted to
      an analysis of variance (ANOVA) and the Tukey test (a=0.05). For the scanning
      electron microscopy (SEM) observation, the exposed pulp chambers (n=5) were
      fixed, dehydrated, dried in a Critical Point dryer, and gold-sputter coated for
      analysis at standardized magnifications (500X, 1000X, and 2000X). RESULTS: None
      of the bleaching techniques reduced the enamel bond strength, the best results
      observed were with the intracoronal treatments with SP and HP. In dentin all
      bleaching techniques reduced the bond strength with the exception of the in
      office HP application technique. The SEM results demonstrated similar dentin
      surfaces for the G1, G3, G6, and G7 groups with more open dentin tubules found
      than in the other groups. CONCLUSION: None of the bleaching techniques tested
      reduced the bond strength of enamel, but they all reduced the bond strength of
      dentin with the exception of the group only treated with in-office bleaching
      using 35% HP. The worst bond strength results to dentin were observed in groups
      that received intracoronal bleaching with SP.

PMID- 18633466
TI  - Smear layer removal and collagen fiber exposure using tetracycline hydrochloride
      conditioning.
AB  - AIM: Smear layer removal and collagen fiber exposure may improve periodontal
      treatment and regeneration. This in vitro study assessed smear layer removal and
      collagen fiber exposure after tetracycline hydrochloride (TTC) application on
      root surfaces using scanning electron microscopy (SEM). METHODS AND MATERIALS:
      Root cementum was removed with diamond burs followed by scaling and root
      planning. Four hundred fifty samples were divided into ten groups: a control
      (saline application) and nine different TTC concentrations were applied at doses
      of 10, 25, 50, 75, 100, 125, 150, 200, and 250 mg/ml. The TTC application was
      performed in all groups in three different ways (passive, brushing, and
      burnishing) and at three different periods of conditioning (1, 2, and 3 minutes).
      A previously trained, calibrated, and blind examiner evaluated photomicrographs
      of the samples using Sampaio's index (2005). Statistical analysis was performed
      using the Kruskal-Wallis' and Dunn's tests. RESULTS: The concentrations of 50
      mg/mL and 75 mg/mL applied by burnishing were the most effective in smear layer
      removal and collagen fiber exposure. Both the passive mode of application
      (p=0.0001) and 1 minute period of application (p=0.002) were the least effective.
      CONCLUSIONS: The concentrations of 50 mg/mL and 75 mg/mL applied by burnishing
      during 2 or 3 minutes were the most effective. CLINICAL SIGNIFICANCE: These
      parameters may be applied in periodontal procedures involving TTC root
      conditioning to optimize results.

PMID- 18633467
TI  - Clinical evaluation of dose reduction on image quality of panoramic radiographs.
AB  - AIM: The purpose of this study was to evaluate the effect of tube current
      reduction on image quality using medium and regular intensifying screens as well
      as a digital system for panoramic radiography. METHODS AND MATERIALS: A total of
      150 panoramic images of 75 patients were obtained in the study. The initial
      images were taken at standard exposure settings, and secondary images were
      exposed with the tube current reduced at different rates. RESULTS: There was no
      statistically significant difference (p>0.05) between the two exposures for Group
      3 (the rate of dose reduction 25%) while a statistically significant difference
      (p<0.05) was found in Group 4 (the rate of dose reduction 50%) using medium
      intensifying screens for all observers. No statistically significant difference
      was found between the two exposures on digital panoramic images. CONCLUSION:
      According to the results of this study a dose reduction of 25% was achieved for
      medium intensifying screens and for digital panoramic images without any loss of
      image quality. CLINICAL SIGNIFICANCE: A substantial reduction in radiation
      exposure can be achieved in conventional panoramic radiography using a medium
      intensifying screen and in digital panoramic radiography without any loss of
      image quality needed for radiological evaluation of anatomical structures and
      pathological conditions.

PMID- 18633468
TI  - The relationships of the maxillary central incisors and canines to the incisive
      papilla in Jordanians.
AB  - AIM: The validity of the relationship between the maxillary anterior teeth and
      the incisive papilla and the pertinence of this relationship to Jordanians was
      examined. METHODS AND MATERIALS: A computerized digital caliper (CDC) tool was
      developed and used in the measurements which were made on scanned images of
      dental casts of 298 Jordanians. The distances from a tangent to the labial
      surface of the central incisors to the midpoint and the posterior border of the
      incisive papilla were measured. The tool was also used in marking the exact point
      on the incisive papilla of the intersection with the line that connected the tips
      of the maxillary canines. The data sets were analyzed statistically and
      comparisons among various sets were drawn at a 95% confidence level. RESULTS:
      Gender had no significant effect on the relationship of the incisive papilla to
      the maxillary anterior teeth, whereas this relationship was significantly
      influenced by the incisal classifications of the examined subjects. CONCLUSION:
      Differences between the Jordanian scores and the Caucasian norms were
      insignificant. CLINICAL SIGNIFICANCE: Therefore, the guidelines recommended for
      Caucasians could be used as starting points in the preliminary location of
      maxillary incisors and canine teeth during construction of dentures for
      Jordanians.

PMID- 18633469
TI  - An analysis of the etiological and predisposing factors related to dentin
      hypersensitivity.
AB  - AIM: To determine the prevalence of different etiological factors of dentin
      hypersensitivity in patients and to provide information on their association with
      dentin hypersensitivity. METHODS AND MATERIALS: Twenty-nine patients (17 male, 12
      female) suffering from pain of dentin hypersensitivity were recruited to
      participate in the study. A relevant history was taken and dentin
      hypersensitivity confirmed by using air-blast and tactile stimuli. RESULTS: All
      patients were right-handed. The left side of the mouth showed a preponderance of
      gingival recession, abrasion, abfraction, and erosion while more teeth on the
      right side showed attrition. Gingival recession and attrition were common among
      the molars, abrasions among the molars and premolars, abfraction among the
      premolars, while erosive lesions were predominantly found among the incisors. A
      total of 911 teeth were examined in the 29 subjects presenting with dentin
      hypersensitivity. The following conditions were found to be associated with the
      dentin hypersensitivity: 43 of 117 teeth (36.8%) with gingival recession; 41 of
      99 teeth (41.4%) with attrition; 40 of 67 teeth (59.7%) with abrasion; 16 of 25
      teeth (64%) with abfraction; and 32 teeth had erosive lesions all associated with
      hypersensitivity. CONCLUSION: Gingival recessions followed by attrition were the
      most commonly found etiological factors leading to dentin hypersensitivity.
      Erosive lesions were mostly associated with dentin hypersensitivity. A
      statistically significant relationship exists between dentin hypersensitivity,
      tooth wear lesions, and gingival recession. CLINICAL SIGNIFICANCE: This study
      provides clinical evidence supporting the notion of dentin hypersensitivity being
      a tooth wear phenomenon. Therefore, successful preventive and management
      strategies for sufferers of dentin hypersensitivity must take into consideration
      causal factors for tooth wear and gingival recession.

PMID- 18633470
TI  - An in vitro evaluation of the antimicrobial activity of nine root canal sealers.
AB  - AIM: The purpose of this in vitro study was to analyze the antimicrobial activity
      of root canal sealers by using the agar diffusion test (ADT). METHODS AND
      MATERIALS: Three categories of root canal sealers were included in the study:
      resin-based sealers (4), zinc oxide-based sealers (3), and calcium hydroxide
      based sealers (2). The microbial strains used were: S. aureus (2 strains), C.
      albicans (2 strains), and E. faecalis (1 strain). Statistical analysis was
      conducted using a one-way analysis of variance (ANOVA). Tests of differences were
      analyzed using the Tukey's test with a value of p < 0.05 considered statistically
      significant. RESULTS: The antimicrobial activity of root canal sealers was ranked
      in descending order as follows: Sealite Regular, Cortisemol, Dentalis KEZ, AH26,
      Sealapex, Acroseal/Topseal, and Endorez/AH plus. CONCLUSION: Root canal sealers
      showed different inhibitory effects depending on their types and the bacterial
      strains tested. Root canal sealers containing formaldehyde and eugenol proved to
      be effective against the microorganisms studied. CLINICAL SIGNIFICANCE: The
      incorporation of antimicrobial components into root canal sealers may become an
      essential factor in preventing the re-growth of residual bacteria and control of
      bacteria re-entry into the root canal system.

PMID- 18633471
TI  - Effectiveness of root canal debris removal using passive ultrasound irrigation
      with chlorhexidine digluconate or sodium hypochlorite individually or in
      combination as irrigants.
AB  - AIM: The aim of this in vitro study was to evaluate the cleaning capacity of
      different auxiliary chemical substances energized with ultrasound in radicular
      dentin using morphologic analysis. METHODS AND MATERIALS: Twenty-eight single
      canal, mandibular incisors were prepared with the Hero 642 canal preparation
      system following the sequence: 25/12, 30/06, 35/02, and 40/02, 1 mm from the
      apex. The specimens were then divided into four groups of seven teeth. During
      biomechanical preparation the teeth were irrigated with 2 ml of distilled water
      between files. Each group of specimens (n=7) received a final irrigation with 100
      ml of the following irrigants that were activated with ultrasound for 3 minutes:
      Group 1- distilled water; Group 2- 0.2% chlorhexidine digluconate (CHX); Group 3-
      2.5% sodium hypochlorite (NaOCl); and Group 4-the filtrate obtained after
      combining 0.2% CHX and 2.5% NaOCl. The apical portions of the root canals from
      each group were then submitted to histological processing and analyzed using
      optical microscopy. RESULTS: Results showed statistical differences between the
      groups (p<0.01). Groups 1 and 2 (distilled water and 0.2% CHX respectively) were
      statistically similar in terms of a greater amount of debris, whereas 2.5% NaOCl
      and the filtrate were more efficient in removal of debris. CONCLUSION: There is
      no additional benefit in terms of debris removal from root canal walls by
      irrigating with the filtrate obtained from the combination of NaOCl and CHX when
      compared to using NaOCl alone. CLINICAL SIGNIFICANCE: The findings of this study
      suggest the time and expense of preparing and using a combination of NaOCl and
      CHX is not warranted compared to using NaOCl alone for root canal irrigation.

PMID- 18633472
TI  - Assessment of oral malodor: a comparison of the organoleptic method with sulfide
      monitoring.
AB  - AIM: The purpose of the present study was to measure the oral malodor of
      volunteers by means of a subjective organoleptic method and a sulfide monitor as
      well as to evaluate the diagnostic value of the Halimeter in the diagnosis of
      halitosis. METHODS AND MATERIALS: Sulfide monitoring and organoleptic oral
      malodor assessment methods were performed on 77 volunteers (51 females, 26 males)
      selected from academic staff, students, clerks, and patients of the Shaheed
      Beheshti University of Medical Sciences and Health Services, Dental School. The
      organoleptic method of assessment and sulphide monitoring were conducted by three
      calibrated judges. The Kendall's tau-b correlation analysis was used to calculate
      correlation coefficients between the sulfide monitor and organoleptic scores.
      RESULTS: The Kendall's correlation coefficient between sulfide monitoring and
      organoleptic scores was 0.493 (p<0.001). Sensitivity and specificity were
      assessed to be 61.1% and 87.8% respectively. The positive predictive value (PPV)
      and the negative predictive value (NPV) were 81.5% and 72%, respectively. The
      intra-class correlation coefficient for the three episodes of monitoring was
      calculated as 97%. CONCLUSION: Use of a sulfide montoring device in conjunction
      with the organoleptic method is an effective strategy for diagnosing oral
      malodor. CLINICAL RELEVANCE: Because of its small size and simplicity of handling
      the Halimeter sulfide monitor is convenient to use. This method of evaluation of
      patients for oral malodor is capable of differentiating normal patients (such as
      with Pseudohalitosis and halitophobia) from the others and for halitosis
      screening along with other techniques such as the organoleptic method. However,
      when used alone, it may lead to a misdiagnosis of some cases in terms of
      intensity.

PMID- 18633473
TI  - Survey of talon cusps in the permanent dentition of a Turkish population.
AB  - AIM: Talon cusp is the name given to the accessory tubercles located on the
      lingual faces of anterior teeth. The occurrence of talon cusps has been reported
      among Europeans and Asians. However, there are few reports of this anomaly in
      Caucasians as well as a paucity of literature on its characteristics. Today there
      are seven million Turkish citizens of Caucasian origin that have settled in the
      Marmara, Central-Anatolia, East-Anatolia, and Black Sea regions of Turkey. The
      aim of this study is to present 27 Caucasian cases with 33 taloned teeth. This
      study is the first that was undertaken to investigate the characteristics of
      talon cusps in a group of Turkish people. METHODS AND MATERIALS: A survey of 27
      patients examined in the Department of Oral Diagnosis and Radiology at Ondokuz
      Mayis University in Samsun, Turkey between January, 2003 and June, 2006 was
      conducted. Their ages ranged from seven to 33 years. A total of 33 talon cusps
      were diagnosed in the 27 patients. The patients' records and radiographs were
      evaluated and the following variables were studied: age, sex distribution,
      affected tooth, type of talon cusp, radiographic evidence of pulp extension, and
      associated dental anomalies and complications. RESULTS: There were 13 male and 14
      female patients with a gender ratio of approximately 1:1. Ten of 33 talon cusps
      (30%) were seen in maxillary right central incisors while four cases (12%) were
      in maxillary left central incisors and nine cases (27%) were in maxillary right
      lateral incisors. Eight cases (24%) were seen in maxillary left lateral incisors,
      one case (3%) was in a mandibular right central incisor, and one case (3%) was in
      a mandibular left canine. Fifteen (15) of the 33 talon cusps were Type 1 talons
      (45%), while eight cases (24%) were Type 2 talons and ten cases (30%) were Type 3
      talons. Twelve of the 33 talon cusps (36%) showed radiographic evidence of pulpal
      extension into the tubercule on periapical radiographs. One patient had
      gemination (3%) on the maxillary permanent incisors and two patients had
      mesiodens (6%) in the maxillary anterior region. CONCLUSION: The talon cusp
      remains as one of the more uncommon dental anomalies worldwide and in Turkey and
      presents with different clinical features. CLINICAL SIGNIFICANCE: The talon cusp
      may be more likely to be associated with other odontogenic anomalies and some
      systemic conditions; early recognition of this anomaly is essential to provide
      proper treatment.

PMID- 18633474
TI  - Preparedness for management of medical emergencies among dentists in Udupi and
      Mangalore, India.
AB  - AIM: The aim of this study was to assess the preparedness for management of
      medical emergencies among dentists in the cities of Udupi and Mangalore in India.
      METHODS AND MATERIALS: A self-administered questionnaire was completed by the
      dental teaching hospital faculty members and private dental practitioners in
      Udupi and Mangalore, India. RESULTS: Less than half (42.1%) of the dentists
      reported having received practical training in management of medical emergencies
      during their undergraduate and postgraduate education. Only about one-third of
      the respondents felt competent in performing mouth-to-mouth breathing (39.3%),
      cardiac compression (35.2%), foreign body obstruction relief (32.8%), and in
      administering IV drugs (34.5%) or supplemental oxygen (27.4%). The most commonly
      available emergency drugs in treatment areas were oral glucose (82.2%) and
      adrenaline (65.8%). However, less than one-fourth of the respondents had the
      following on hand in their treatment facility: oxygen (24.0%), an AMBU bag
      (17.1%), pocket mask (13.0%), bronchodilator spray (24.7%), diazepam (20.5%),
      aspirin (20.5%), and glyceryl trinitrate (17.8%). Less than half (39%) of the
      respondents reported having clinical staff members trained to assist in emergency
      recognition and management and only 5.8% carried out emergency drills in their
      workplace. CONCLUSION: Preparedness for management of medical emergencies was
      found to be inadequate among the surveyed dentists. CLINICAL SIGNIFICANCE: The
      results of the study emphasize the need for improvement of the training of
      practicing dentists in the management of medical emergencies at the
      undergraduate, postgraduate, and continuing education levels as well as the need
      for organization of the dental workplace to handle such emergencies.

PMID- 18633475
TI  - Breast adenocarcinoma mimicking temporomandibular disorders: a case report.
AB  - AIM: The aim of this report is to present a case of a metastatic lesion in the
      mandible originating from a breast adenocarcinoma that was initially diagnosed as
      temporomandibular disorder (TMD). The role of the dental practitioner in the
      diagnostic phases is also discussed. BACKGROUND: It is not uncommon to see a
      patient who complains of what seems to be a TMD but who in reality suffers from a
      systematic disease, dental infection, or neoplasia. Although metastases to the
      head and neck are uncommon, it should always be considered among the differential
      diagnoses of lesions. REPORT: A 42-year-old female presented with pain and
      swelling in the right temporomandibular joint (TMJ) previously diagnosed as TMD.
      Further clinical, radiological, and histological examinations coupled with a
      history of adenocarcinoma of the breast lead to a final diagnosis of a metastatic
      lesion in the right TMJ region. SUMMARY: In most patients who present with an
      oral metastasis the distant primary tumor has already been diagnosed and treated.
      Occasionally the discovery of an oral metastasis leads to the detection of an
      occult primary malignancy elsewhere in the body. Thus the dentist should be able
      to perform an adequate diagnosis and play an important role in the diagnostic
      phase of care that can lead to a useful palliation and an enhanced quality of the
      patient's life. CLINICAL SIGNIFICANCE: In order to avoid the pitfalls so common
      in evaluating patients with TMJ pain, the clinician must perform a complete and
      critical review of the medical history along with a comprehensive examination.
      The challenge is to know and evaluate the differential diagnosis. Failure to do
      so can result in a misdiagnosis which may lead to unnecessary care, long-term
      therapy without clinical resolution, or potentionally death.

PMID- 18633476
TI  - Glanzmann thrombasthenia: a rare hematological disorder with oral manifestations:
      a case report.
AB  - AIM: The aim of this report is to present a case of Glanzmann thrombasthenia (GT)
      with oral manifestations requiring periodontal management along with a discussion
      of the clinical, hematologic, and molecular level features of the disease.
      BACKGROUND: GT is a rare hematological disorder with oral manifestations
      affecting platelets and clotting. It is characterized by spontaneous bleeding
      from mucosal tissues and excessive bleeding following skin damage. It belongs to
      the group of hereditary platelet disorders and is due to a defect in one of two
      genes, platelet membrane glycoprotein (GP) IIb/IIIa. REPORT: A 22-year-old female
      patient with a history of Type I GT and long-term care using platelet transfusion
      was referred for management of her gingival bleeding. Dental treatment included
      scaling, polishing, oral hygiene instructions, along with a prescription for anti
      plaque agents. There was pronounced improvement in her periodontal condition
      after treatment. Reduced gingival bleeding resulted in an increase in her
      hemoglobin level from a pre-treatment level of 2 gm% to 8 gm% during her last
      visit. The patient was followed for eight months with no further periodontal
      complications. SUMMARY: A pronounced improvement in the periodontal condition of
      a GT patient occurred following routine scaling and polishing procedures along
      with proper oral hygiene maintenance instructions. The result was a reduction of
      the patient's gingivitis and associated spontaneous bleeding and an improvement
      in her hemoglobin status. GT patients should be managed for their periodontal
      problems following a hematological consultation. The importance of proper
      maintenance of oral hygiene as well as regular recall visits should be
      emphasized.

PMID- 18633477
TI  - Implant-supported crowns for a shortened dental arch: a case report.
AB  - AIM: The aim of this report is to highlight the efficiency of implant restoration
      of a shortened dental arch (SDA) for a partially edentulous patient. BACKGROUND:
      The SDA refers to a dentition with loss of posterior teeth. The goal of dental
      care is the maintenance of a natural dentition with regard to esthetics, speech,
      chewing, and oral comfort. In order to achieve this goal several issues were
      examined in a SDA clinical scenario including masticatory ability, occlusal
      factors, the effect of removable partial dentures, oral comfort, and periodontal
      support. REPORT: A 62-year-old female with a SDA presented for treatment with
      concern about her compromised periodontal and restorative status. Following
      professional scaling and root planing and oral hygiene motivation, the bite was
      opened. Restorative treatment was rendered up to the second premolars with the
      issues associated with a SDA in mind. SUMMARY: A body of evidence in literature
      showed an arch extending to the second premolars is adequate for normal
      functional demands, oral hygiene, oral comfort, and possibly reduced costs on a
      dentition subjected to modern diet. The reported clinical outcomes of using
      implant supported crowns till the second premolar area using the concept of
      restoring only an existing SDA were highly satisfactory for the well-oriented
      patient.

PMID- 18633478
TI  - How to deal with esthetically overcritical patients who need complete dentures: a
      case report.
AB  - AIM: The purpose of this report is to present a strategy for making a diagnosis
      and providing appropriate treatment for denture patients with high esthetic
      demands. BACKGROUND: Some edentulous patients have critical requirements for the
      esthetic aspect of dentures. REPORT: A 55-year-old edentulous female presented
      with a complaint of dissatisfaction with the appearance of two sets of old
      dentures. A complex method was used during the fabrication of a new set of
      dentures in order to meet her demand for esthetics. SUMMARY: This method
      essentially improves the mutual communication and cooperation between dentists
      and patients; therefore, it improves satisfaction of the patients.

PMID- 18633479
TI  - How chromatin remodelling allows shuffling of immunoglobulin heavy chain genes.
AB  - Cellular identity is determined by the switching on and off of lineage-specific
      genes. This dynamic process is regulated by a highly co-ordinated series of
      chromatin remodelling mechanisms that control DNA accessibility to facilitate
      transcription, replication and recombination. The identity of an individual B
      lymphocyte is defined by the expression of a unique antibody protein, composed of
      two identical immunoglobulin heavy and two identical light chain polypeptides,
      which recognize a single foreign antigen with high specificity. However, the
      mammalian adaptive immune system requires an enormous variety of antibody
      expressing B cells to combat the millions of foreign antigens it may encounter.
      This diversity is generated primarily at the multigene immunoglobulin loci by
      V(D)J recombination, a specialised form of DNA recombination in which numerous
      variable (V), diversity (D) and joining (J) genes are cut and pasted together in
      a strict order to allow shuffling of immunoglobulin genes. The mouse
      immunoglobulin heavy chain (Igh) locus is the largest known multigene locus. It
      spans approximately 3 Mb and comprises more than 200 genes. Its size and
      complexity pose an enormous logistic challenge to the chromatin remodelling
      machinery, but recent major advances in our understanding of how the 200 genes
      are shuffled have begun to reveal an exquisitely co-ordinated set of chromatin
      remodelling mechanisms which exploit every aspect of nuclear dynamics, and
      provide a global view of multigene regulation. This review will explore the
      numerous processes implicated in opening up and positioning of the locus to
      enable shuffling of the Igh locus genes, including non-coding RNA transcription,
      histone modifications, transcription factors, nuclear relocation and locus
      contraction.

PMID- 18633481
TI  - Microbial cholesterol oxidases: bioconversion enzymes or signal proteins?
AB  - Cholesterol oxidases (3beta-hydroxysterol oxidases; EC 1.1.3.6), serve as
      catalysts for the initial step in the degradation of cholesterol, and probably
      other natural sterols, that are used as carbon sources for growth of different
      bacteria. Because of their suitability for attacking cholesterol they have been
      widely used for the quantification of cholesterol in clinical and food specimens.
      Cholesterol oxidase has also found application as a probe for membrane structure,
      as an insecticide, and has been implicated in bacterial pathogenesis. Recently,
      we have found that a Streptomyces cholesterol oxidase is required for the
      biosynthesis of the antifungal polyene pimaricin, apparently acting as an
      antifungal sensor. Here we describe our current understanding of these
      fascinating enzymes.

PMID- 18633480
TI  - Regulation of stress hormones jasmonates and ethylene by MAPK pathways in plants.
AB  - Plant stress hormones, such as jasmonates (JAs) and ethylene (ET) are essential
      in plant defence against stress conditions. JAs are used in cosmetics and food
      flavouring, and the recently demonstrated anti-cancer activity of JAs highlights
      their potential in health protection. It reinforces the need for a better
      understanding of biosynthetic regulation of JAs. Which mechanisms are involved in
      the regulation of the biosynthesis of JAs and ET? Production of stress hormones
      is induced in plants after wounding or herbivore attack. ET is a gaseous compound
      and plant JAs are oxylipins structurally similar to prostaglandins that are
      induced upon inflammation or injury in mammals. Wounding activates protein
      phosphorylation cascades involving mitogen-activated protein kinases (MAPKs).
      MAPKs regulate ET production. The induction of JA biosynthesis was suggested to
      require MAPK activation; however the defined roles of MAPKs in JA production
      remain unclear. Here we will highlight the most recent findings suggesting the
      regulation of JA biosynthesis and ethylene production by stress activated MAPKs
      and phosphatases that inactivate these MAPKs.

PMID- 18633482
TI  - Urinary proteomics: towards biomarker discovery, diagnostics and prognostics.
AB  - During recent years, the proteomics field has moved onward to clinical
      applications, particularly for biomarker discovery, diagnostics and prognostics
      of human diseases. The urine is one of the ideal clinical samples for such
      applications because it is readily available in almost all patients, and its
      collection is very simple and non-invasive. Urinary proteomics thus becomes one
      of the most interesting subdisciplines in the clinical proteomics area. This
      article highlights and updates recent progress in the urinary proteomics field
      for clinical applications.

PMID- 18633483
TI  - Mass spectrometric analysis of cross-linking sites for the structure of proteins
      and protein complexes.
AB  - Mass spectrometry has become the method of choice to detect and quantify the
      minute amounts of proteins at the genomic scale. It has recently been adopted for
      three dimensional structure analyses of proteins or protein complexes by
      chemically cross-linking their intact forms and analyzing the cross-linked pieces
      after digestion. This highlight provides an overview of the technology with a
      focus on advances in the last two years. This cross-linking mass spectrometry has
      a great potential to become a powerful tool to supplement current X-ray and NMR
      method of protein structure analysis.

PMID- 18633484
TI  - Stress-related and spontaneous stage differentiation of Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligatory intracellular parasitic protozoan that infects
      a variety of avian and mammalian hosts including up to one third of the human
      population worldwide. Developmental differentiation between distinct stages, i.e.
      sporozoites, tachyzoites and bradyzoites is fundamental for the parasite life
      cycle and for transmission between hosts. It is also interconnected with the
      pathogenesis of overt toxoplasmosis and makes T. gondii an important
      opportunistic pathogen of humans. In order to delineate the underlying
      mechanisms, several cell culture differentiation systems have been developed
      which mimic the transition from fast-replicating tachyzoites to slowly
      proliferating bradyzoites in vitro. Since exogenous stress factors, i.e. alkaline
      pH, IFN-gamma and other proinflammatory cytokines, chemicals or drugs, heat
      shock, and deprivation of nutrients have been shown to increase the efficacy of
      bradyzoite development in vitro, Toxoplasma stage differentiation is largely
      viewed as a stress-related response to hostile environmental conditions. However,
      tachyzoite to bradyzoite differentiation also occurs spontaneously in vitro and
      this raises questions about the importance of stress conditions for triggering
      stage conversion. High frequencies of spontaneous bradyzoite development in
      primary and permanent skeletal muscle cells, i.e. cells that preferentially
      harbour bradyzoite-containing tissue cysts in vivo suggest that the host cell
      type may be critical. Furthermore, the host cell transcriptome, including the
      expression of distinct host cell genes, has recently been shown to trigger
      bradyzoite development and cyst formation. Together, these results strongly
      indicate that the complex cellular environment, besides exogenous stress factors,
      may govern the developmental differentiation of T. gondii.

PMID- 18633485
TI  - Cadherins in development and cancer.
AB  - Proper embryonic development is guaranteed under conditions of regulated cell
      cell and cell-matrix adhesion. The cells of an embryo have to be able to
      distinguish their neighbours as being alike or different. Cadherins, single-pass
      transmembrane, Ca(2+)-dependent adhesion molecules that mainly interact in a
      homophilic manner, are major contributors to cell-cell adhesion. Cadherins play
      pivotal roles in important morphogenetic and differentiation processes during
      development, and in maintaining tissue integrity and homeostasis. Changes in
      cadherin expression throughout development enable differentiation and the
      formation of various organs. In addition to these functions, cadherins have
      strong implications in tumourigenesis, since frequently tumour cells show
      deregulated cadherin expression and inappropriate switching among family members.
      In this review, I focus on E- and N-cadherin, giving an overview of their
      structure, cellular function, importance during development, role in cancer, and
      of the complexity of Ecadherin gene regulation.

PMID- 18633486
TI  - Binding of a dinuclear ruthenium(ii) complex to the TAR region of the HIV-AIDS
      viral RNA.
AB  - Molecular modelling has identified a new RNA conformational feature created by
      the insertion of bulge residues into duplex regions that may act as a recognition
      site for small molecule binding, in particular for inert dinuclear ruthenium
      complexes.

PMID- 18633487
TI  - Metabonomic study on ageing: NMR-based investigation into rat urinary metabolites
      and the effect of the total flavone of Epimedium.
AB  - The aim of this work was to investigate the effects of ageing on rat urinary
      metabolites and to evaluate the anti-ageing effects of the total flavone of
      Epimedium (TFE). Proton nuclear magnetic resonance based metabonomic analyses was
      performed on urine from rats aged 4, 10, 18 and 24 months, and rats administered
      with TFE. By multivariate analysis, 26 characteristic resonances were found to be
      highly related with the age of rats, and ten of them were structurally postulated
      as creatinine, lactate, alanine, acetate, acetone, succinate, allantoin,
      methylamine, dimethylamine and trimethylamine-N-oxide; these metabolites involve
      creatinine metabolites, aliphatic amines metabolites and some important
      intermediates or end products of energy metabolism. Principal components analysis
      revealed that the metabolic profiles of 24-month-old rats treated with TFE
      closely resembled those of rats aged 18 months. In addition, most of these
      characteristic resonances were reset to younger levels by TFE intervention. The
      result suggests that TFE administration can markedly influence the ageing process
      and shows anti-ageing effects, which might due to the melioration of pyruyate
      metabolism and oxidative phosphorylation.

PMID- 18633488
TI  - Characterization of a randomized FRET library for protease specificity
      determination.
AB  - Protease specificity determination is an important first step when characterizing
      novel proteases. Given the large number of proteases that are known to exist from
      genomic sequencing efforts, we reason that sensitive, reliable, and high
      throughput methods to determine protease specificity must be developed. This
      study describes the construction and initial characterization of a protein based
      FRET library using the fluorescent proteins GFP and DsRed for such a purpose.
      Using a DNA "cassette" that allowed for directional insertion of annealed
      oligonucleotides between the genes encoding the GFP and DsRed proteins, we
      constructed a library using a mixture of standard nucleotide bases at 27
      positions in the center of the oligonucleotide cassette. This resulted in a
      randomized linker region between these fluorescent donor-acceptor pairs to
      produce substrates with varied amino acids located between the proteins. Kinetic
      assays were then performed and monitored using the increase in GFP fluorescence
      to arrive at relative reaction velocities for a set of enzymes. These results
      demonstrated the ability of the enzymes tested to discriminate between different
      substrates and the resistance of GFP and DsRed to proteolysis. Colony screening,
      using color development and restriction enzyme digests, were shown to help
      eliminate DNA samples in the library that contained stop codons and/or deletions
      and a flow plan for the efficient use of the library is presented.

PMID- 18633489
TI  - Modelling room temperature ionic liquids.
AB  - Room temperature ionic liquids (IL) composed of organic cations and inorganic
      anions are already being utilized for wide-ranging applications in chemistry.
      Complementary to experiments, computational modelling has provided reliable
      details into the nature of their interactions. The intra- and intermolecular
      structures, dynamic and transport behaviour and morphologies of these novel
      liquids have also been explored using simulations. The current status of
      molecular modelling studies is presented along with the prognosis for future work
      in this area.

PMID- 18633490
TI  - E factors, green chemistry and catalysis: an odyssey.
AB  - The development of green chemistry is traced from the introduction of the
      concepts of atom economy (atom utilisation) and E factors in the early 1990s. The
      important role of catalysis in reducing or eliminating waste is emphasised and
      illustrated with examples from heterogeneous catalytic oxidations with hydrogen
      peroxide, homogeneous catalytic oxidations and carbonylations and organocatalytic
      oxidations with stable N-oxy radicals. Catalytic reactions in non-conventional
      media, e.g. aqueous biphasic, supercritical carbon dioxide and ionic liquids, are
      presented. Biotransformations involving non-natural reactions of enzymes, e.g.
      ester ammoniolysis, and the rational design of semi-synthetic enzymes, such as
      vanadate phytase, are discussed. The optimisation of enzyme properties using in
      vitro evolution and improvement of their operational stability by immobilisation
      as cross-linked enzyme aggregates (CLEA) are presented. The ultimate in green
      chemistry is the integration of catalytic steps into a one-pot, catalytic cascade
      process. An example of a chemoenzymatic synthesis of an enantiomerically pure
      amino acid in water and a trienzymatic cascade process using a triple-decker
      oxynitrilase/nitrilase/amidase CLEA are discussed. Finally, catalytic conversions
      of renewable raw materials are examined and the biocatalytic aerobic oxidation of
      starch to carboxy starch is presented as an example of green chemistry in optima
      forma i.e. a biocompatible product from a renewable raw material using a
      biocatalytic air oxidation.

PMID- 18633491
TI  - Covalent modification of a metal-organic framework with isocyanates: probing
      substrate scope and reactivity.
AB  - Isoreticular metal-organic framework-3 (IRMOF-3) has been postsynthetically
      modified with isocyanates to generate unprecedented, microporous urea
      functionalized frameworks.

PMID- 18633492
TI  - Specific N-terminal protein labelling: use of FMDV 3C pro protease and native
      chemical ligation.
AB  - We report an effective strategy for generating N-terminal cysteinyl proteins by
      proteolytic cleavage using the enzyme 3C pro, suitable for a wide range of
      applications via native chemical ligation.

PMID- 18633493
TI  - Fullerene-encapsulated porphyrin hexagonal nanorods. An anisotropic donor
      acceptor composite for efficient photoinduced electron transfer and light energy
      conversion.
AB  - We have successfully constructed fullerene-encapsulated porphyrin hexagonal
      nanorods in DMF-acetonitrile solution mixed with CTAB surfactant, which
      demonstrate efficient and characteristic photoinduced electron transfer and light
      energy conversion properties.

PMID- 18633494
TI  - Hollow porphyrin prisms: modular formation of permanent, torsionally rigid
      nanostructures via templated olefin metathesis.
AB  - Hollow, hexa-porphyrin prisms of two sizes were template-assembled and covalently
      locked, via cross-olefin metathesis, into permanent, torsionally rigid structures
      whose active sites (metal sites) can be both accessed and altered in a facile
      manner.

PMID- 18633495
TI  - A flexible tripodal ligand linking octametallic terbium rings into luminescent
      polymeric chains.
AB  - Six bidentate building blocks have been used to form a tripodal ligand with a
      flexible C3 symmetric spacer to direct the assembly of large octametallic
      clusters covalently linked to form a 1-D highly luminescent terbium tube-like
      polymer.

PMID- 18633496
TI  - Isopropyllithium diamine adducts: from a non symmetric aggregate to monomeric i
      PrLi.(1R,2R)-N,N,N',N'-tetraethylcyclohexane-1,2-diamine.
AB  - By means of isopropyllithium crystal structures, the transition from dimeric (i
      PrLi.TMEDA)2 (4) to monomeric i-PrLi.(R,R)-TECDA (6) via the non-symmetric
      aggregate [(i-PrLi)3.(TEEDA)2] (5) is shown, depending on the steric demand of
      the ligand.

PMID- 18633497
TI  - Concurrent anion...pi interactions between a perchlorate ion and two pi-acidic
      aromatic rings, namely pentafluorophenol and 1,3,5-triazine.
AB  - The rational design of a ligand containing two electron-poor pi-rings, i.e. a
      triazine and a pentafluorophenoxy groups, has allowed the preparation of a copper
      complex where both the anticipated anion...pi interactions are present.

PMID- 18633498
TI  - FRET-based sensor for imaging chromium(III) in living cells.
AB  - On the basis of fluorescent resonance energy transfer from 1,8-naphthalimide to
      rhodamine, a fluorophore dyad (FD8) containing rhodamine and a naphthalimide
      moiety was synthesized as a Cr3+-selective fluorescent probe for monitoring Cr3+
      in living cells with ratiometric fluorescent methods.

PMID- 18633499
TI  - Unprecedented cationic copper(I)-iodide aggregates trapped in "click" formation
      of anionic-tetrazolate-based coordination polymers.
AB  - A series of unprecedented cationic copper(i)-iodide aggregates, (Cu4I2)2+,
      (Cu6I2)4+ and (Cu10I4)6+, are trapped in the in situ formation of anionic
      tetrazolate-based coordination polymers, namely [Cu2(mu3-I)(mu5-Cpta)]n (1),
      [Cu5(mu4-I)(mu4-Mtta)3(CN)]n (2) and [Cu5(mu6-I)(mu2-I)(mu4-Mtta)3](n) (3) [Cpta
      = 5-(3-cyanophenyl)tetrazolate, Mtta = 5-methyltetrazolate], which exhibit
      structure-related green, cyan and blue luminescence, respectively.

PMID- 18633501
TI  - A polyoxometalate-based manganese carboxylate cluster.
AB  - The functionalization of a pre-formed, high oxidation state {CeIV MnIV 6} cluster
      with a lacunary phosphotungstate, [alpha-P2 W15 O 56]12-, exemplifies a
      straightforward route for grafting redox-active building blocks to existing Mn
      carboxylate clusters and modeling their deposition onto metal oxide surfaces.

PMID- 18633500
TI  - Single base interrogation by a fluorescent nucleotide: each of the four DNA bases
      identified by fluorescence spectroscopy.
AB  - Nucleoside C, which contains a rigid nitroxide spin label, is effectively reduced
      in DNA by sodium sulfide to the corresponding amine, yielding a fluorescent probe
      (Cf) that can report the identity of its base-pairing partner in duplex DNA.

PMID- 18633502
TI  - Can a synthetic thread act as an electrochemically switchable molecular device?
AB  - Here we report that at room temperature in acetonitrile after the reduction of
      the naphthalimide-site, a synthetic molecular thread undergoes a complete
      conformational change which makes possible an efficient conversion of chemical
      energy into mechanical work; such results point out the ability of the thread to
      act as a molecular device under electrochemical control.

PMID- 18633503
TI  - Crystal-to-crystal transformation from a chain polymer to a two-dimensional
      network by thermal desolvation.
AB  - Single-crystal to single-crystal transformation of a new lead(II) coordination
      polymer with ligands 8-hydroxyquinoline (8-Quin) and nitrate, [Pb2(8
      Quin)2(NO3)2(MeOH)] () to [Pb(8-Quin)(NO3)] (1beta), is reported and the
      structures of and determined by X-ray crystallography.

PMID- 18633504
TI  - Rhodium-catalyzed (E)-selective cross-dimerization of terminal alkynes.
AB  - Cross-dimerization of various terminal alkynes with different bulky terminal
      alkynes such as triisopropylsilylacetylene and 1-trimethylsilyloxy-1,1-diphenyl-2
      propyne efficiently proceeds in the presence of a rhodium catalyst system to
      produce the corresponding (E)-enynes with high regio- and stereoselectivity.

PMID- 18633505
TI  - Double decarboxylative Claisen rearrangement reactions: microwave-assisted de
      novo synthesis of pyridines.
AB  - Microwave-assisted double decarboxylative Claisen rearrangement of bis(allyl) 2
      tosylmalonates provides substituted 1,6-heptadienes, which may be alkylated, and
      then converted into pyridines by ozonolysis followed by reaction with ammonia
      generated in situ under microwave conditions.

PMID- 18633506
TI  - Stepwise elongation effect on the two-photon absorption of self-assembled
      butadiyne porphyrins.
AB  - Butadiyne-porphyrin dimer arrays, which were generated by complementary
      coordination of the central zinc atom to imidazolyl followed by metathesis, were
      elongated stepwise and their 2PA properties were explored.

PMID- 18633507
TI  - One-pot synthesis of Ag-Fe3O4 nanocomposite: a magnetically recyclable and
      efficient catalyst for epoxidation of styrene.
AB  - With the assistance of PVP, a novel magnetically recyclable Ag-based catalyst has
      been synthesized in one pot, and it is found that this catalyst is highly
      efficient in selectively catalyzing styrene conversion to styrene oxide.

PMID- 18633508
TI  - Selective one-pot synthesis of various phenols from diarylethanes.
AB  - Various substituted phenols were selectively synthesized by a one-pot reaction
      through the NHPI-catalyzed aerobic oxidation of 1,1-diarylethanes followed by
      treatment with dilute sulfuric acid.

PMID- 18633509
TI  - Single-pot triple catalytic transformations based on coupling of in situ
      generated allyl boronates with in situ hydrolyzed acetals.
AB  - In situ hydrolyzed acetals were coupled with in situ generated allyl boronates in
      a one-pot procedure, affording regio- and stereodefined homoallyl alcohols,
      epoxides and amino alcohols.

PMID- 18633510
TI  - Synthesis of 4a-carba-alpha-D-lyxofuranose from 2,3-O-isopropylidene-L
      erythruronolactone via Tebbe-mediated cascade reaction.
AB  - A new, efficient and highly diastereoselective approach for the synthesis of
      1,2,3,5-tetraacetylcarba-alpha-D-lyxofuranose from D-ribose is reported via one
      pot conversion of to using Tebbe reagent which involves a cascade reaction
      sequence of methylenation, cleavage of isopropyl group, carbocyclization and
      again methylenation.

PMID- 18633511
TI  - A dynamic micromixer for arbitrary control of disguised chemical selectivity.
AB  - A new type of dynamic micromixer combining the concepts of parallel multi
      lamination and hydrodynamic focusing was developed for arbitrary control of
      disguised chemical selectivity.

PMID- 18633512
TI  - Tuning of hole doping level of iodine-encapsulated single-walled carbon nanotubes
      by temperature adjustment.
AB  - We present a simple approach of tuning the hole doping level of iodine-doped
      single-walled carbon nanotubes by adjusting temperature, utilizing the structural
      conversion of iodine species encapsulated in SWNTs.

PMID- 18633513
TI  - A two-directional approach to the anatoxin alkaloids: second synthesis of
      homoanatoxin and efficient synthesis of anatoxin-a.
AB  - Total syntheses of the potent neurotoxins, environmental hazards, and biochemical
      probes anatoxin-a and homoanatoxin have been achieved from a common intermediate
      using a combined two-directional synthesis-tandem reaction strategy which
      includes key advances in oxidative desymmetrisation, tandem Michael
      intramolecular Mannich cyclisations and a new method for deprotection of N-tosyl
      anatoxin-a.

PMID- 18633514
TI  - Tracking reactive intermediates in phosphine-promoted reactions with ambiphilic
      phosphino-boranes.
AB  - The ambiphilic phosphino-borane i-Pr2P(o-C6H4)BMes2 affords stable versions of
      key zwitterionic intermediates by reactions with diethyl azodicarboxylate or
      PhNCO.

PMID- 18633515
TI  - Multidentate thioether ligands coating gold nanoparticles.
AB  - The design and synthesis of oligomeric ligands based on benzylic thioethers is
      presented together with their ability to enwrap and stabilize gold nanoparticles
      with diameters below 2 nm, which become--with increasing length of the oligomer-
      more monodisperse and stable.

PMID- 18633516
TI  - Molecular recognition in a heteromolecular radical pair system with complementary
      multipoint hydrogen-bonding.
AB  - Stable radicals 2-(6-uradinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1
      oxyl (Ur6IN) and 4-(p-tert-butylaminoxylphenyl)-2,6-di(propylamido)pyridine
      (DAPPN) form heterospin radical pair complexes due to complementary multi-point
      hydrogen-bonds.

PMID- 18633517
TI  - Synthesis and characterization of a smart contrast agent sensitive to calcium.
AB  - A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been
      synthesized and characterized. The agent shows approximately 100% relaxivity
      enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+
      also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in
      physiological fluids prove the prospects of the agent for in vivo measurements.

PMID- 18633518
TI  - Stable supramolecular helical structure of C6-symmetric hydrogen-bonded
      hexakis(phenylethynyl)benzene derivatives with amino acid pendant groups and
      their unique fluorescence properties.
AB  - A highly stable supramolecular helical structure was formed by the self-assembly
      of novel C6-symmetric hydrogen-bonded discotic molecules,
      hexakis(phenylethynyl)benzene derivatives with chiral alanine parts, and
      exhibited orange excimer emission with a large Stokes shift.

PMID- 18633519
TI  - The tert-butyl group in chemistry and biology.
AB  - The unique reactivity pattern elicited by the crowded tert-butyl group is
      highlighted by summarising characteristic applications. Starting from the use of
      this simple hydrocarbon moiety in chemical transformations, via its relevance in
      Nature and its implication in biosynthetic and biodegradation pathways, the way
      through to its possible application in biocatalytic processes is described.

PMID- 18633520
TI  - Enzymatic N-methylaminoacylation of tRNA using chemically misacylated AMP as a
      substrate.
AB  - Using "chemically misacylated AMP" which is photogeneratable, tRNA can be
      enzymatically acylated with N-methylamino acids in an efficiency comparable to
      that of the corresponding natural aminoacylation process with amino acids.

PMID- 18633521
TI  - The azaquinone-methide elimination: comparison study of 1,6- and 1,4-eliminations
      under physiological conditions.
AB  - The azaquinone-methide elimination is a powerful and efficient reaction useful
      for disassembly of spacers in prodrug systems. We and others have used the spacer
      technique to develop dendritic and polymeric self-immolative molecular systems
      that can disassemble through a domino-like mechanism upon a stimulus event. In
      this report, we study the disassembly of a system that can disintegrate through
      para- and ortho-azaquinone-methide eliminations. The disassembly was evaluated
      with molecules that undergo single 1,6- or 1,4-elimination and with molecules
      that undergo double 1,6- and 1,4-elimination. The 1,6-elimination was slightly
      faster than the 1,4-elimination under physiological conditions. This study sheds
      light on the disassembly-behavior of prodrug systems.

PMID- 18633522
TI  - Stereoselective desymmetrisation of prochiral alpha,alpha-dicyanoalkenes via
      domino Michael-Michael addition reactions.
AB  - The desymmetrisation of prochiral alpha,alpha-dicyanoalkenes via tandem Michael
      Michael addition reactions with alpha,beta-unsaturated ketones catalysed by 9
      amino-9-deoxyepicinchona alkaloids was investigated, from which bicyclic products
      bearing four stereogenic centers were afforded in a single operation with high
      stereoselectivities (>99% de, up to >99.5% ee).

PMID- 18633523
TI  - A new type of self-supported, polymeric Ru-carbene complex for homogeneous
      catalysis and heterogeneous recovery: synthesis and catalytic activities for ring
      closing metathesis.
AB  - A novel 2nd generation Grubbs-type catalyst tethering an isopropoxystyrene has
      been synthesized and automatically polymerized in solution to form a self
      supported polymeric Ru-carbene complex, which catalyzed ring-closing metathesis
      homogeneously, but was recovered heterogeneously.

PMID- 18633524
TI  - An efficient synthesis of triazolo-carbohydrate mimetics and their conformational
      analysis.
AB  - A chemical library of 1,2,3-triazole fused carbohydrate mimetics was constructed.
      To synthesize enantiomerically pure mimetics, we developed a stereo- or
      diastereodivergent synthetic route from D-glucose, D-mannose and D-galactose as
      chiral sources. In this synthesis, an In(OTf)(3)-catalyzed tandem azidation-1,3
      dipolar cycloaddition reaction of 1,1-dimethoxyhex-5-yne derivatives with TMSN(3)
      was used as the key step to construct the 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5
      a]pyridine framework. Additionally, NMR was used to carry out a conformational
      analysis of the synthesized mimetics, which are of structural interest since they
      have an N,O-acetal moiety in place of the anomeric position of normal
      pyranosides.

PMID- 18633525
TI  - Toward solution-phase automated iterative synthesis: fluorous-tag assisted
      solution-phase synthesis of linear and branched mannose oligomers.
AB  - We report herein the first synthesis of linear and branched mannose
      oligosaccharides using fluorous-tag assistance with reagents and FSPE protocols
      that are amenable to automation. The particular fluorous linker proved to
      maintain solubility of the growing oligosaccharide chain such that identical
      reaction solvent conditions and purification protocols could be used between
      glycosylation and deprotection reactions, thereby rendering the procedures
      amenable to automation.

PMID- 18633526
TI  - Reagent switchable stereoselective beta(1,2) mannoside mannosylation: OH-2 of
      mannose is a privileged acceptor.
AB  - The discovery of novel conditions for highly beta-stereoselective (>9 : 1)
      mannosylation of OH-2 of mannosides using a straightforward
      perbenzylthioglycoside donor has allowed ready assembly of beta-mannosyl
      oligosaccharides including the repeating trisaccharide motif of the O5 antigen of
      pathogen Klebsiella pneumoniae.

PMID- 18633527
TI  - Layer-by-layer deposition of molecular oligoelectrolytes-investigation of
      assembling and degradation behaviour.
AB  - The assembly and degradation behavior of oligoelectrolyte multilayer films (OEMs)
      self assembled by layer-by-layer deposition of positively and negatively charged
      oligoelectrolytes 1-6 was investigated. Next to colorless oligoelectrolytes we
      have employed representatives involving chromophores, in particular porphyrins.
      This allows for the systematic observation of both assembly and disassembly of
      the OEMs using optical spectroscopy, where chromophore containing building blocks
      serve as reporter electrolytes. The OEMs investigated in this study were built in
      a consistent, monomolecular matter and show linear correlation between the
      absorption and the number of layers. Using the concept of reporter electrolytes
      we have introduced for the first time also the use of non-chromophoric
      oligoelectrolytes, such as the new synthesized cationic system 2 as building
      blocks for OEMs. Moreover, we have investigated for the first time the
      degradation behavior of OEMs. We demonstrated that two different mechanisms of
      degradation proceed at the same time. The direct degradation is accompanied by a
      second release mechanism.

PMID- 18633528
TI  - 2, 3-Diaryl-5-ethylsulfanylmethyltetrahydrofurans as a new class of COX-2
      inhibitors and cytotoxic agents.
AB  - 2,3-Diaryl-5-ethylsulfanylmethyltetrahydrofuran-3-ols were designed and
      synthesized by the allylations of benzoins followed by iodocyclization and
      nucleophilic replacement reactions with ethanthiol. These molecules exhibit
      IC(50) for COX-2 at <10 nM concentration and exhibit average GI(50) over all the
      59 human tumor cell lines at microM concentration.

PMID- 18633529
TI  - Antioxidant activity of (+)-bergenin: a phytoconstituent isolated from the bark
      of Sacoglottis uchi Huber (Humireaceae).
AB  - (+)-Bergenin (1) was isolated from Sacoglottis uchi, a species of vegetable found
      in the Amazon region and popularly used for the treatment of several hepatic
      problems. The structure of 1 was fully characterized using IR, GC-MS and NMR (1D
      and 2D) analyses. This phytoconstituent has been used as an oriental folk
      medicine for the treatment of many diseases and shows antihepatotoxic properties.
      Tests with beta-carotene, DPPH and a heterogeneous Fenton system were carried
      out, confirming the antioxidant activity of 1. Theoretical calculations were
      performed to investigate the formation of the radical derivatives of 1 using *H,
      *OH, *CH(3), and *CCl(3) as initiator radicals. DFT thermodynamic calculations
      showed that the methoxyl group (O-6-CH(3)) is the most favorable site for radical
      attack. Frontier molecular orbital analysis showed that nucleophilic radical
      attack is favored on the aromatic ring of 1 where the LUMO is localized, with
      antibonding character with respect to the O-6-CH(3) bond. The possibilities of
      attack at other sites on 1 were investigated in detail in order to understand the
      regiospecificity of this reaction.

PMID- 18633530
TI  - Inhibitors of the kinase IspE: structure-activity relationships and co-crystal
      structure analysis.
AB  - Enzymes of the non-mevalonate pathway for isoprenoid biosynthesis are therapeutic
      targets for the treatment of important infectious diseases. Whereas this pathway
      is absent in humans, it is used by plants, many eubacteria and apicomplexan
      protozoa, including major human pathogens such as Plasmodium falciparum and
      Mycobacterium tuberculosis. Herein, we report on the design, preparation and
      biological evaluation of a new series of ligands for IspE protein, a kinase from
      this pathway. These inhibitors were developed for the inhibition of IspE from
      Escherichia coli, using structure-based design approaches. Structure-activity
      relationships (SARs) and a co-crystal structure of Aquifex aeolicus IspE bound to
      a representative inhibitor validate the proposed binding mode. The crystal
      structure shows that the ligand binds in the substrate-rather than the adenosine
      5'-triphosphate (ATP)-binding pocket. As predicted, a cyclopropyl substituent
      occupies a small cavity not used by the substrate. The optimal volume occupancy
      of this cavity is explored in detail. In the co-crystal structure, a diphosphate
      anion binds to the Gly-rich loop, which normally accepts the triphosphate moiety
      of ATP. This structure provides useful insights for future structure-based
      developments of inhibitors for the parasite enzymes.

PMID- 18633531
TI  - The aza-analogues of 1,4-naphthoquinones are potent substrates and inhibitors of
      plasmodial thioredoxin and glutathione reductases and of human erythrocyte
      glutathione reductase.
AB  - Various aza-analogues of 1,4-naphthoquinone and menadione were prepared and
      tested as inhibitors and substrates of the plasmodial thioredoxin and glutathione
      reductases as well as the human glutathione reductase. The replacement of one to
      two carbons at the phenyl ring of the 1,4-naphthoquinone core by one to two
      nitrogen atoms led to an increased oxidant character of the molecules in
      accordance with both the redox potential values and the substrate efficiencies.
      Compared to the 1,4-naphthoquinone and menadione, the quinoline-5,8-dione 1 and
      both quinoxaline-5,8-diones 5 and 6 behaved as the most efficient subversive
      substrates of the three NADPH-dependent disulfide reductases tested. Modulation
      of these parameters was observed by alkylation of the aza-naphthoquinone core.

PMID- 18633532
TI  - Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN
      lectin.
AB  - DC-SIGN, a lectin, which presents at the surface of immature dendritic cells,
      constitutes nowadays a promising target for the design of new antiviral drugs.
      This lectin recognizes highly glycosylated proteins present at the surface of
      several pathogens such as HIV, Ebola virus, Candida albicans, Mycobacterium
      tuberculosis, etc. Understanding the binding mode of this lectin is a topic of
      tremendous interest and will permit a rational design of new and more selective
      ligands. Here, we present computational and experimental tools to study the
      interaction of di- and trisaccharides with DC-SIGN. Docking analysis of complexes
      involving mannosyl di- and trisaccharides and the carbohydrate recognition domain
      (CRD) of DC-SIGN have been performed. Trisaccharides Manalpha1,2[Manalpha1,6]Man
      1 and Manalpha1,3[Manalpha1,6]Man 2 were synthesized from an orthogonally
      protected mannose as a common intermediate. Using these ligands and the soluble
      extracellular domain (ECD) of DC-SIGN, NMR experiments based on STD and transfer
      NOE were performed providing additional information. Conformational analysis of
      the mannosyl ligands in the free and bound states was done. These studies have
      demonstrated that terminal mannoses at positions 2 or 3 in the trisaccharides are
      the most important moiety and present the strongest contact with the binding site
      of the lectin. Multiple binding modes could be proposed and therefore should be
      considered in the design of new ligands.

PMID- 18633533
TI  - Synthesis of aryl-substituted 2-pyridyl-1,10-phenanthrolines; a series of
      oriented terpyridine analogues.
AB  - A 3 x 3 matrix of manisyl (4-methoxy-2,6-dimethylphenyl) substituted pyridyl-1,10
      phenanthrolines has been synthesized by utilizing a general palladium catalyzed
      cross-coupling procedure. The directionality of these terdentate ligands will
      generate chiral octahedral ML(2) complexes, potentially useful for the metal
      templated synthesis of topologically chiral structures.

PMID- 18633534
TI  - Trachycladindoles A-G: cytotoxic heterocycles from an Australian marine sponge,
      Trachycladus laevispirulifer.
AB  - A southern Australian marine sponge, Trachycladus laevispirulifer, yielded the
      cytotoxic agents trachycladindoles A-G (1-7) as a selection of novel indole-2
      carboxylic acids bearing a 2-amino-4,5-dihydroimidazole moiety. The
      trachycladindoles displayed promising selective cytotoxicity against a panel of
      human cancer cell lines and their structures were assigned on the basis of
      detailed spectroscopic analysis. Preliminary structure activity relationship
      (SAR) investigations by co-metabolite defined structural features key to the
      trachycladindole pharmacophore, highlighting an unusual bioactive molecular motif
      deserving of future investigation.

PMID- 18633535
TI  - Preparation of leukotriene B(4) inhibitory active 2- and 3-(2-aminothiazol-4
      yl)benzo[b]furan derivatives and their growth inhibitory activity on human
      pancreatic cancer cells.
AB  - A series of 2-(2-aminothiazol-4-yl)benzo[b]furan and 3-(2-aminothiazol-4
      yl)benzo[b]furan derivatives were prepared, and their leukotriene B(4) inhibitory
      activity and growth inhibitory activity in cancer cell lines were evaluated.
      Several compounds showed strong inhibition of calcium mobilization in CHO cells
      overexpressing human BLT(1) and BLT(2) receptors and growth inhibition to human
      pancreatic cancer cells MIA PaCa-2. 3-(4-Chlorophenyl)-2-[5-formyl-2
      [(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 8b showed the
      most potent and selective inhibition for the human BLT(2) receptor, and its
      IC(50) value was smaller than that of the selected positive control compound, ZK
      158252. 3-(4-Chlorophenyl)-2-[2-[(dimethylamino)methyleneamino]-5-(2
      hydroxyethyliminomethyl)thiazol-4-yl]-5-methoxybenzo[b]furan 9a displayed growth
      inhibitory activity towards MIA PaCa-2.

PMID- 18633537
TI  - Direct chlorination of alcohols with chlorodimethylsilane catalyzed by a gallium
      trichloride/tartrate system under neutral conditions.
AB  - The reaction of secondary alcohols 1 with chlorodimethylsilane (HSiMe(2)Cl)
      proceeded in the presence of a catalytic amount of GaCl(3)/diethyl tartrate to
      give the corresponding organic chlorides 3. In the catalytic cycle, the reaction
      of diethyl tartrate 4a with HSiMe(2)Cl 2 gives the chlorosilyl ether 5 with
      generation of H(2). Alcohol-exchange between the formed chlorosilyl ether 5 and
      the substrate alcohol 1 affords alkoxychlorosilane 6, which reacts with catalytic
      GaCl(3) to give the chlorinated product 3. The moderate Lewis acidity of GaCl(3)
      facilitates chlorination. Strong Lewis acids did not give product due to
      excessive affinity for the oxy-functionalities. Although tertiary alcohols were
      chlorinated by this system even in the absence of diethyl tartrate, certain
      alcohols that are less likely to give carbocationic species were effectively
      chlorinated using the GaCl(3)/diethyl tartrate system.

PMID- 18633536
TI  - A concise and straightforward total synthesis of (+/-)-salinosporamide A, based
      on a biosynthesis model.
AB  - A 14-step total synthesis of (+/-)-salinosporamide A (1), a potent inhibitor of
      the 20S proteasome isolated from the marine bacterium Salinospora tropica, is
      described. The synthesis is based on a diastereoselective intramolecular
      aldolisation of a substituted beta-keto amide intermediate, i.e. 13, derived from
      a beta-keto acid, viz. 21, and an alpha-amino malonate, leading to the
      pyrrolidinone ring 24 in the natural product. This synthetic approach closely
      mimics the origin of the pyrrolidinone ring in salinosporamide A in vivo. Another
      key feature of the total synthesis is a regioselective reduction of the malonate
      derivative 31 to the key aldehyde intermediate 32, using Super-hydride.

PMID- 18633538
TI  - Kinetic resolution of esters via metal catalyzed methanolysis reactions.
AB  - Some chiral lanthanide complexes of the Schiff base adducts of: a) bis(2
      pyridylcarboxaldehyde) and (1R),(2R)-trans-1,2-diaminocyclohexane (Pyr-R,R'-chxn:
      3); b) 6-methyl-2-pyridylcarboxaldehyde and (1R),(2R)-trans 1,2
      diaminocyclohexane (MePyr-chxn, 4); and c) 2,6-pyridyldicarboxaldehyde and
      (1R),(2R)-trans-1,2-diaminocyclohexane ((Pyr-R,R'-chxn)(2), 5) have been screened
      for their utility to promote kinetic resolution via metal catalyzed alcoholyses
      of the p-nitrophenyl esters of chiral D- and L-Boc-protected glutamine and
      phenylalanine. Solvents were varied to optimize the kinetic selectivity values,
      defined as k(2)(L)/k(2)(D) or k(2)(D)/k(2)(L), for the methanolysis and in some
      cases, ethanolysis of these substrates. At ambient temperature the greatest
      selectivity was found for the ethanolysis of Boc-Gln-OPNP, catalyzed by
      3:Yb(3+):((-)OEt) (k(2)(L)/k(2)(D) = 7.2). The greatest selectivity for Boc-Phe
      OPNP is k(2)(D)/k(2)(L) = 3.9 for its methanolysis promoted by 5:La(3+):((-)OMe).
      A kinetic method is introduced for the determination of both d and l rate
      constants for catalyzed alcoholysis from a single kinetic experiment. The
      activation parameters DeltaH(double dagger) and DeltaS(double dagger) were
      determined for the metal catalyzed methanolysis and ethanolysis of the Boc-Gln
      OPNP substrates, and selectivity factors were found to increase at lower
      temperatures. A low temperature time course for the ethanolysis of racemic Boc
      Gln-OPNP catalyzed by 3:Yb(3+):((-)OEt) at -15 degrees C indicated that after 3
      hours 60% residual d-enantiomer was observed having an enantiomeric excess of
      >95% ee. The activation parameters for the ethanolysis of the same substrate
      catalyzed by (Pyr-R,R'-chxn)(2):La(3+):((-)OEt) predict a k(2)(D)/k(2)(L) = 40.4
      at -40 degrees C with a large ee of >99% with approximately 80% of l isomer
      remaining at that temperature which has been experimentally confirmed.

PMID- 18633540
TI  - Generation and hetero-Diels-Alder reactions of an o-quinone methide under mild,
      anionic conditions: rapid synthesis of mono-benzannelated spiroketals.
AB  - Deprotonation of o-hydroxybenzyl acetate with (i)PrMgCl provides a method of
      generating an o-quinone methide under mild, anionic conditions, such that highly
      sensitive exo-enol ethers can be employed as 2pi partners in hetero-Diels-Alder
      reactions. This process results in mono-benzannelated spiroketals such as those
      found in the natural products berkelic acid, the chaetoquadrins or cephalostatin
      6.

PMID- 18633539
TI  - Synthesis of azoxabicyclo[3.3.1]nonanones based on diastereoselective reactions
      of 1,1-bis(trimethylsilyloxy)ketene acetals with isoquinolines and quinolines.
AB  - Densely functionalized azoxabicyclo[3.3.1]nonanones were prepared by regio- and
      diastereoselective condensation of 1,1-bis(silyloxy)ketene acetals with
      isoquinolinium and quinolinium salts and subsequent regioselective and
      stereospecific iodolactonization.

PMID- 18633541
TI  - Development of a practical Buchwald-Hartwig amine arylation protocol using a
      conveniently prepared (NHC)Pd(R-allyl)Cl catalyst.
AB  - Continuing efforts to establish a more general "user-friendly" protocol for the
      palladium-catalysed arylation of amines (Buchwald-Hartwig reaction) are described
      herein. Significant advances have been made through the use of the versatile
      (SIPr)Pd(methallyl)Cl complex in conjunction with the reliable base lithium
      hexamethyldisilazide (LHMDS).

PMID- 18633542
TI  - Field-dependent ion transport in disordered solid electrolytes.
AB  - We have carried out experimental and theoretical studies of the electric field
      dependent ion transport in disordered materials and in disordered potential
      landscapes, respectively. In our experiments, we work in an electric field range
      up to 100 kV cm(-1), which is characterised by a weak nonlinear response of the
      mobile ions. We detect remarkable differences between different ion-conducting
      glasses regarding the temperature dependence of the nonlinear response.
      Theoretically, we study one-dimensional hopping models and continuous disordered
      potential models, respectively. When comparing theoretical and experimental data,
      we find both analogies and discrepancies.

PMID- 18633544
TI  - Room temperature ionic liquids containing low water concentrations-a molecular
      dynamics study.
AB  - We have performed classical molecular dynamics to study the properties of a water
      miscible and a water-immiscible room-temperature ionic liquid when mixed with
      small quantities of water. The two ionic liquids consist of the same 1-ethyl-3
      methylimidazolium ([EMIM]) cation combined with either the boron tetrafluoride
      ([BF(4)]) or bis(trifluoromethylsulfonyl)imide ([NTf(2)]) anion. It is found
      that, in both ionic liquids, water clusters of varying sizes are typically
      hydrogen bonded to two anions with the cation playing a minor role. We also
      highlight the difficulties of obtaining dynamic quantities such as self-diffusion
      coefficients from simulations of such viscous systems.

PMID- 18633543
TI  - Unfolding and melting of DNA (RNA) hairpins: the concept of structure-specific 2D
      dynamic landscapes.
AB  - A 2D free-energy landscape model is presented to describe the (un)folding
      transition of DNA/RNA hairpins, together with molecular dynamics simulations and
      experimental findings. The dependence of the (un)folding transition on the stem
      sequence and the loop length is shown in the enthalpic and entropic contributions
      to the free energy. Intermediate structures are well defined by the two
      coordinates of the landscape during (un)zipping. Both the free-energy landscape
      model and the extensive molecular dynamics simulations totaling over 10 mus
      predict the existence of temperature-dependent kinetic intermediate states during
      hairpin (un)zipping and provide the theoretical description of recent ultrafast
      temperature-jump studies which indicate that hairpin (un)zipping is, in general,
      not a two-state process. The model allows for lucid prediction of the collapsed
      state(s) in simple 2D space and we term it the kinetic intermediate structure
      (KIS) model.

PMID- 18633545
TI  - QM/MM studies of Ni-Fe hydrogenases: the effect of enzyme environment on the
      structure and energies of the inactive and active states.
AB  - The catalytically active (Ni-SI and Ni-R) and inactive states (Ni-A and Ni-B) of
      Ni-Fe hydrogenases have been studied using density functional theory (DFT)
      methods. Both isolated clusters and clusters embedded in the enzyme have been
      used to model the Ni-A, Ni-B, Ni-SI and Ni-R states. The BP86 and B3LYP
      functionals were employed, and hybrid quantum mechanical (QM)/molecular
      mechanical (MM) methods were used for the embedded calculations. The QM/MM
      studies, rather than the isolated cluster calculations, were generally found to
      give structures which correlated better with X-ray data. The structure of the
      unready state (Ni-A), was correctly predicted by the QM/MM, but not by the
      isolated cluster calculation. Comparison with the observed crystal structure
      favoured the catalytically active state, Ni-SI, to be the protonated (Ni-SI(II)),
      rather than the unprotonated state (Ni-SI(I)). In the QM/MM studies, the binding
      of H(2) to Ni-SI(II) is preferred at the Ni (Ni-R(Ni)), rather than at the Fe
      centre (Ni-R(Fe)), in agreement with xenon binding studies, and in contrast to
      isolated cluster studies. These calculations cannot say with certainty which
      functional should be favoured, nor the preferred spin state of the catalytically
      active species. However, the lack of any predicted structure in which H(2) binds
      to the Fe centre, does favour a low spin state for Ni-SI(II), and the use of the
      BP86 functional. This is in agreement with recent high level ab initio
      calculations of a model of the Ni-SI(I) state.

PMID- 18633546
TI  - The electronic properties of an oxygen vacancy at ZrO(2)-terminated (001)
      surfaces of a cubic PbZrO(3): computer simulations from the first principles.
AB  - Combining B3PW hybrid exchange-correlation functional within the density
      functional theory (DFT) and a supercell model, we calculated from the first
      principles the electronic structure of both ideal PbZrO(3) (001) surface (with
      ZrO(2)- and PbO-terminations) and a neutral oxygen vacancy also called the F
      center. The atomic relaxation and electronic density redistributions are
      discussed. Thermodynamic analysis of pure surfaces indicates that ZrO(2)
      termination is energetically more favorable than PbO-termination. The O vacancy
      on the ZrO(2)-surface attracts approximately 0.3 e (0.7 e in the bulk PbZrO(3)),
      while the remaining electron density from the missing O(2-) ion is localized
      mostly on atoms nearest to a vacancy. The calculated defect formation energy is
      smaller than in the bulk which should lead to the vacancy segregation to the
      surface. Unlike Ti-based perovskites, the vacancy-induced (deep) energy level
      lies in PbZrO(3) in the middle of the band gap.

PMID- 18633547
TI  - Sub-picosecond time resolved infrared spectroscopy of high-spin state formation
      in Fe(ii) spin crossover complexes.
AB  - The photoinduced low-spin (S = 0) to high-spin (S = 2) transition of the iron(ii)
      spin-crossover systems [Fe(btpa)](PF(6))(2) and [Fe(b(bdpa))](PF(6))(2) in
      solution have been studied for the first time by means of ultrafast transient
      infrared spectroscopy at room temperature. Negative and positive infrared
      difference bands between 1000 and 1065 cm(-1) that appear within the instrumental
      system response time of 350 fs after excitation at 387 nm display the formation
      of the vibrationally unrelaxed and hot high-spin (5)T(2) state. Vibrational
      relaxation is observed and characterized by the time constants 9.4 +/- 0.7 ps for
      [Fe(btpa)](PF(6))(2)/acetone and 12.7 +/- 0.7 ps for both
      [Fe(btpa)](PF(6))(2)/acetonitrile and [Fe(b(bdpa)](PF(6))(2)/acetonitrile.
      Vibrational analysis has been performed via DFT calculations of the low-spin and
      high-spin state normal modes of both compounds as well as their respective
      infrared absorption cross sections. The simulated infrared difference spectra are
      dominated by an increase of the absorption cross section upon high-spin state
      formation in accordance with the experimental infrared spectra.

PMID- 18633548
TI  - Investigation of the radical product channel of the CH(3)C(O)CH(2)O(2) + HO(2)
      reaction in the gas phase.
AB  - The reaction of CH(3)C(O)CH(2)O(2) with HO(2) has been studied at 296 K and 700
      Torr using long path FTIR spectroscopy, during photolysis of
      Cl(2)/acetone/methanol/air mixtures. The branching ratio for the reaction channel
      forming CH(3)C(O)CH(2)O, OH and O(2) () was investigated in experiments in which
      OH radicals were scavenged by addition of benzene to the system, with subsequent
      formation of phenol used as the primary diagnostic for OH radical formation. The
      observed prompt formation of phenol under conditions when CH(3)C(O)CH(2)O(2)
      reacts mainly with HO(2) indicates that this reaction proceeds partially by
      channel , which forms OH both directly and indirectly, by virtue of secondary
      generation of CH(3)C(O)O(2) (from CH(3)C(O)CH(2)O) and its reaction with HO(2)
      (). The secondary generation of OH radicals was confirmed by the observed
      formation of CH(3)C(O)OOH, a well-established product of the CH(3)C(O)O(2) +
      HO(2) reaction (via channel ). A number of delayed sources of OH also contribute
      to the observed phenol formation, such that full characterisation of the system
      required simulations using a detailed chemical mechanism. The dependence of the
      phenol and CH(3)C(O)OOH yields on the initial peroxy radical precursor reagent
      concentration ratio, [methanol](0)/[acetone](0), were well described by the
      mechanism, consistent with a small but significant fraction of the reaction of
      CH(3)C(O)CH(2)O(2) with HO(2) proceeding via channel . This allowed a branching
      ratio of k(3b)/k(3) = 0.15 +/- 0.08 to be determined. The results therefore
      provide strong indirect evidence for the participation of the radical-forming
      channel of the title reaction.

PMID- 18633549
TI  - A bond-bond description of the intermolecular interaction energy: the case of
      weakly bound N(2)-H(2) and N(2)-N(2) complexes.
AB  - The atom-bond pairwise additive approach, recently introduced by us to describe
      the potential energy surface for atom-molecule cases, is extended here for the
      first time to molecule-molecule systems. The idea is to decompose the van der
      Waals interaction energy into bond-bond pair contributions. This must be
      considered an improvement with respect to the familiar atom-atom pairwise
      additive representation since, still using a simple formulation, it indirectly
      accounts for three body effects. Such an approach also allows to include, in a
      straightforward way, the effect of the bond length on the intermolecular
      interaction energy. Cases of study are the weakly bound complexes involving the
      H(2) and N(2) molecules, namely N(2)-H(2) and N(2)-N(2), here described as a
      single bond-bond pair. For both systems ab initio calculations and experimental
      molecular beam scattering data, as well as second virial coefficients, have been
      employed to test the accuracy of the chosen representation of the interaction and
      to improve the obtained potential energy surfaces. The results of this work are
      important also for the generalization to the cases involving molecular ions and
      polyatomic molecules.

PMID- 18633550
TI  - Mechanisms for the formation of secondary organic aerosol components from the gas
      phase ozonolysis of alpha-pinene.
AB  - Gas-phase ozonolysis of alpha-pinene was studied in static chamber experiments
      under 'OH-free' conditions. A range of multifunctional products-in particular low
      volatility carboxylic acids-were identified in the condensed phase using gas
      chromatography coupled to mass spectrometry after derivatisation. The dependence
      of product yields on reaction conditions (humidity, choice of OH radical
      scavengers, added Criegee intermediate scavengers, NO(2)etc.) was investigated to
      probe the mechanisms of formation of these products; additional information was
      obtained by studying the ozonolysis of an enal and an enone derived from alpha
      pinene. On the basis of experimental findings, previously suggested mechanisms
      were evaluated and detailed gas-phase mechanisms were developed to explain the
      observed product formation. Atmospheric implications of this work are discussed.

PMID- 18633551
TI  - Experimental and modelling study of the recombination reaction H + O(2) (+M) -->
      HO(2) (+M) between 300 and 900 K, 1.5 and 950 bar, and in the bath gases M = He,
      Ar, and N(2).
AB  - The recombination reaction H + O(2) (+M) --> HO(2) (+M) was studied by laser
      flash photolysis in a high pressure flow cell, over the temperature range 300-900
      K, the pressure range 1.5-950 bar and in the bath gases M = He and N(2). Earlier
      experiments by Hahn et al. (Phys. Chem. Chem. Phys. 2004, 6, 1997) in the bath
      gas M = Ar were also extended. The data were analyzed in terms of unimolecular
      rate theory employing new calculations of relevant molecular parameters. Improved
      energy transfer parameters for the bath gases M = He, Ar, N(2), and H(2)O could
      thus be obtained and complete falloff curves were constructed. In the case of
      water, the high pressure rates well connect with pulse radiolysis results
      obtained in supercritical water by Janik et al. (J. Phys. Chem. A 2007, 111, 79).

PMID- 18633552
TI  - Electrodeposited polymer films with both superhydrophobicity and
      superoleophilicity.
AB  - Electrodeposited films of poly(ethylenedioxythiophene) (PEDOT) present a rough
      morphology and are wettable by water and oil. The covalent binding of low free
      energy fluorinated chains on the monomer before polymerization lowers the surface
      energy of the electroformed polymers sufficiently to give rise to
      superhydrophobic behaviour while conserving superoleophilicity. It holds the
      promise of an interesting candidate for the separation of water and oil.

PMID- 18633553
TI  - Thermal induced phase transitions and structural relaxation in apoferritin
      encapsulated copper nanoparticles.
AB  - Nanocrystalline metals display interesting basic and technological properties
      related to their chemical and structural properties. Among other properties, they
      display a richer phase diagram due to the additional degree of freedom introduced
      by the nanoparticles surface. Metal nanoparticles encapsulated within biological
      macromolecules have the additional advantage of biocompatibility. In this paper
      we investigate the thermal evolution of the structure and dynamics of apoferritin
      encapsulated nanocrystalline copper. We determined the occurrence of a yet
      unexpected phase transition from a low temperature FCC to a complex high
      temperature phase including a (putative) amorphous precursor. The occurrence of a
      FCC-icosahedral transition is also discussed as a possible explanation to our
      results. The lattice dynamics of the FCC phase (monitored by its Debye
      temperature) differs from the behaviour expected for nanosized structures.

PMID- 18633554
TI  - Thermodynamic properties of ionic liquids-a cluster approach.
AB  - We describe a method for calculating thermodynamic properties of ionic liquids by
      using standard quantum statistical thermodynamics as characterized by ab initio
      techniques. We review briefly how thermochemical properties for different sized
      clusters of ionic liquids are calculated by standard ab initio programs. The
      cluster partition functions allow one to calculate energies, enthalpies and Gibbs
      energies. Assuming that the ionic liquid exists exclusively as isolated ion-pairs
      in the gaseous phase and regarding the largest clusters as possible liquid
      structures, we could estimate vapor pressures, enthalpies of vaporization and
      entropies of vaporization. For possible boiling points it is shown how they vary
      with pressure.

PMID- 18633555
TI  - Triaminoguanidinium dinitramide-calculations, synthesis and characterization of a
      promising energetic compound.
AB  - The highly energetic compound 1,3,5-triaminoguanidinium dinitramide (1) was
      prepared in high yield (82%) according to a new synthesis by the reaction of
      potassium dinitramide and triaminoguanidinium perchlorate. The heat of formation
      was calculated in an extensive computational study (CBS-4M). With this the
      detonation parameters of compound were computed using the EXPLO5 software: D =
      8796 m s(-1), p = 299 kbar. In addition, a full characterization of the chemical
      properties (single X-ray diffraction, IR and Raman spectroscopy, multinuclear NMR
      spectroscopy, mass spectrometry and elemental analysis) as well as of the
      energetic characteristics (differential scanning calorimetry, thermal safety
      calorimetry, impact, friction and electrostatic tests) is given in this work. Due
      to the high impact (2 J) and friction sensitivity (24 N) several attempts to
      reduce these sensitivities were performed by the addition of wax. The performance
      of was tested applying a "Koenen" steel sleeve test resulting in a critical
      diameter of > or =10 mm.

PMID- 18633556
TI  - Night-time cough in children with acute wheezing and with upper respiratory tract
      infection.
AB  - AIMS: To evaluate night-time cough patterns in children with either acute
      wheezing or an URTI, and to correlate them to the clinical diagnosis. METHODS:
      Night-time cough variables of 49 children diagnosed with acute wheezing and with
      URTI were compared using a portable cough monitoring instrument placed in the
      child's room. RESULTS: Children with acute wheezing had significantly more coughs
      per night, a longer duration of cough sounds, a higher number of coughing bouts
      per night, and a higher number of coughs per second within a bout, than children
      with an URTI. Children with acute wheezing coughed significantly more between
      23.00 and 01.00, whereas between 01.00 and 06.00 there was no significant
      difference in the number of coughs between the two groups. CONCLUSIONS:
      Significant differences were found in night-time cough variables between children
      with an acute episode of wheezing and children with an URTI. This could be useful
      in clinical practice.

PMID- 18633557
TI  - Transient obturator neuropathy due to local anesthesia during transobturator
      sling placement.
AB  - The transobturator tape procedure is a popular minimally invasive procedure to
      treat stress urinary incontinence. A 42-year-old woman with stress urinary
      incontinence underwent a transobturator sling under intravenous sedation and
      local injection with a mixture of 0.5% bupivicaine and 1% lidocaine with
      1:200,000 epinephrine. After surgery, she had difficulty with adduction of the
      left leg, consistent with a left obturator neuropathy, which improved after
      approximately 12 h and completely resolved by the next day. Although the
      transobturator tape is an effective, minimally invasive procedure that may be
      performed on an outpatient basis, caution should be used in the dosage, type, and
      amount of local anesthesia used. Post-operative obturator paralysis can be
      expectantly managed as the symptoms should resolve after the local anesthesia
      wears off.

PMID- 18633558
TI  - Vesicovaginal fistula repair using tunneled gluteal cutaneous fat-pad flap.
AB  - Tissue interposition in vesicovaginal repair is associated with better cure rates
      especially in failed repairs. Commonly used tissues include the labial fat pad in
      transvaginal approach and vascularized omental, peritoneal flaps or ileal patch
      in transabdominal approach. We report a case of a failed vesicovaginal fistula
      buttressed with a gluteal cutaneous flap.

PMID- 18633559
TI  - Preferences and concerns for delivery: an antepartum survey.
AB  - Little is known regarding patient preferences for method of delivery despite
      concern about rising cesarean section rates. We hypothesize that the majority of
      pregnant women desire a vaginal birth. An anonymous survey was distributed to
      pregnant women assessing demographics, pregnancy history, delivery preference,
      and concern for outcomes. Five-hundred fifty respondents completed the survey;
      43% were nulliparous. The majority preferred vaginal delivery (89.6%). Reasons
      included reduced recovery pain (72%), scars (68%), and bleeding (48%). Cesarean
      deliveries were believed to cause more maternal injuries (39%), but affect sexual
      function less (35%). Nulliparas were more concerned about vaginal support damage
      (p = .005), sexual function changes (p < or = 0.001), and need for episiotomy (p
      < or = .001). Despite this, 93% of nulliparas chose vaginal birth. Increased
      parity was associated with preference for cesarean delivery (r = 0.108, p =
      0.013). Despite nulliparas' concerns about complications of vaginal delivery, the
      majority of pregnant women would choose vaginal birth.

PMID- 18633560
TI  - The effectiveness of supportive underwear in women with pelvic organ prolapse: a
      pilot study.
AB  - The objective was to assess the effectiveness of supportive underwear (Pro
      Portare) in women with pelvic organ prolapse. Symptomatic women with all stages
      of prolapse participated in the study and were followed up for 4 weeks. The
      effectiveness of Pro-Portare was measured by three validated disease-specific
      quality-of-life questionnaires, a daily diary and a questionnaire on comfort and
      effectiveness. Thirteen women were included in the study. No improvement on
      quality of life was found with the use of Pro-Portare. None of the women regarded
      Pro-Portare as very effective, whereas five women regarded the device as
      (reasonably) effective. The women's major concern was on the size, shape and hard
      consistency of the inlet. Two women experienced worsening of their prolapse. Pro
      Portare was not effective in the alleviation of prolapse symptoms and was no
      final solution in any of the women.

PMID- 18633561
TI  - An extremely rare bifurcation pattern of the caudal abdominal aorta: case report
      demonstrated by angiography.
AB  - An extremely rare bifurcation pattern at the caudal abdominal aorta was
      encountered on the pelvic angiography and MR angiography of a male patient.
      Instead of dividing into two common iliac arteries, the caudal abdominal aorta
      first gave the right external iliac artery at the level of the last lumbar
      arteries, then bifurcated into a right internal iliac artery and a left common
      iliac artery. The median sacral artery originated at this anomalous bifurcation.
      This high origin of the right external iliac artery and separate branching of
      these right iliac vessels from the abdominal aorta are important during the
      interventions in the region. We present the angiography findings and discuss the
      embryological origin of this unusual and unreported congenital anomaly.

PMID- 18633562
TI  - Quantified relationships of the radial nerve with the radial groove and selected
      humeral landmarks.
AB  - Anatomical relationships between the radial nerve, the deltoid muscle insertions
      and several bony landmarks have been investigated to assess the feasibility of
      surgical transfer of the deltoid transfer during humeral osteotomy. Eleven
      embalmed human specimens were dissected. Each specimen included the whole thorax,
      both shoulders and upper limbs. Spatial position of the radial nerve along the
      radial groove, the deltoid muscle, and several anatomical landmarks was digitised
      using a three-dimensional (3D) digitiser. Sixteen distances and one angle
      characterizing the relationships between the path of the radial nerve and the
      landmarks were processed. Results showed that the average distance between the
      emergence of the radial nerve from the lateral intermuscular septum and the most
      distal insertion point of the deltoid muscle on the humeral bone shaft was 47.6
      +/- 18.5 mm. The angle between a line extending from the entry of the radial
      nerve into the radial sulcus and its point of emergence (REN-REM line), and on
      the other hand a line running from the radial emergence and the deltoid muscle
      tip (REM-DELTIP line) was in average 23.5 +/- 6.7 degrees . The length of four
      lines running perpendicular to REM-DELTIP and crossing each quarter of the REN
      REM line were interpolated. The length of these four lines was, from proximal to
      distal, 31.3 +/- 11.5 mm; 23.0 +/- 7.8 mm; 16.5 +/- 6.2 mm; and 7.6 +/- 2.6 mm,
      respectively. These results described in a quantitative way the path of the
      radial nerve in respect to the humeral bone and the deltoid muscle. These data
      will be used for further development of a humeral osteotomy protocol taking into
      account the spatial position of the radial nerve to orientate safely the surgical
      tools used to cut the humeral shaft.

PMID- 18633563
TI  - The posterior talofibular ligament: an anatomical study with clinical implication
      in clubfoot surgery.
AB  - BACKGROUND: The role of the posterior talofibular ligament (PTFL) in the clubfoot
      deformity remains unclear. We conducted an anatomical study to precise its
      topography and role in maintaining tibiotalar equinus in patients with clubfoot
      deformity. METHODS: Ten ankles were dissected using a wide posterior exposure.
      The PTFL was identified at the posterior aspect of the ankle and its relations
      with other anatomical structures were noted. RESULTS: After opening of the
      tibiotalar and subtalar joints, the superior aspect of the PTFL was clearly seen,
      running horizontally from the fibula to a prominent tubercle on the posterior
      surface of the talus. The tibiotalar and subatalar joint capsules joined together
      laterally on the posterior edge of the PTFL and medially on the posterior part of
      the talus. A fibrous structure identified as being the "tibial slip" was noted in
      four cases between the posterior medial aspect of the lateral malleolus and the
      tibiotalar posterior capsule. Two different groups of fibers were identified
      inside the PTFL. CONCLUSIONS: Correcting the equinus and inversion of the talus
      needed an extensive release of soft tissues of the posterior part of the ankle.
      Our description of both short anterior and long posterior fibers of the PTFL
      improved our comprehension of functional anatomy of this ligament. We have found
      that PTFL is part of a posterior joint complex between the tibiotalar and
      subtalar joint. The posterior joint complex is a heritage of ankle evolution from
      a prehensile to a weight-bearing joint pattern. The inferior tibiofibular
      transverse ligament, the tibial slip and the calcaneofibular ligament are
      interpreted as derivatives of this ancestral meniscus and stabilize the weight
      bearing ankle. Because the posterior fibers of the PTFL and the tibial slip are
      part of the complex, they should be excised like the posterior capsules during
      clubfoot surgery.

PMID- 18633564
TI  - Incidence of accessory ossicles and sesamoid bones in the feet: a radiographic
      study of the Turkish subjects.
AB  - Most accessory ossicles and sesamoid bones of the ankle and the foot remain
      asymptomatic; however, they have increasingly been examined in the radiology
      literature, because they can cause painful syndromes or degenerative changes in
      response to overuse and trauma. Our aim was to document a detailed investigation
      on the accessory ossicles and sesamoid bones of Turkish subjects in both the feet
      according to the sex, frequency and division of the bones, coexistence and
      bilaterality by radiography. A double-centered study was performed
      retrospectively to determine the incidence of the accessory ossicles and sesamoid
      bones in the ankle and foot. Accessory ossicles (21.2%) and sesamoid bones (9.6%)
      were detected by Radiographs of 984 subjects. The most common accessory ossicles
      were accessory navicular (11.7%), os peroneum (4.7%), os trigonum (2.3%), os
      supranaviculare (1.6%), os vesalianum (0.4%), os supratalare (0.2%), os
      intermetatarseum (0.2%). We observed bipartite hallux sesamoid in 2.7% of
      radiographs. Interphalangeal sesamoid bone of the hallux was seen in 2% of
      radiographs. Incidences of metatarsophalangeal sesamoid bones were found as 0.4%
      in the second digit, 0.2% third digit, 0.1% fourth digit and 4.3% fifth digit. We
      also identified the coexistencies of two different accessory ossicles as 6%,
      accessory ossicles and sesamoid bones as 7%, and bipartite sesamoid bones and
      sesamoid bones as 1.9%. Distribution of the most common accessory ossicles in
      male and female subjects was similar. We reported the incidence of accessory
      ossicles and sesamoid bones of the feet in Turkish adult population.

PMID- 18633565
TI  - Levosimendan for bridging in a pediatric patient with Alstrom syndrome awaiting
      heart-lung transplantation.

PMID- 18633566
TI  - Immunoadsorption in a 40 year old man with dilated cardiomyopathy and underlying
      active myocarditis.

PMID- 18633567
TI  - Demand for open heart surgery due to entrapment of a circular mapping catheter in
      the mitral valve in a patient undergoing atrial fibrillation ablation.

PMID- 18633568
TI  - The pipeline: preparing and training pulmonary scientists for research careers.
AB  - New technologies have made this an opportune time to prepare and embark on an
      academic career in respiratory disease research. The pulmonary physician
      scientist has a special advantage to take basic research findings to the
      patient's illness and impact medical care. But is there a sufficient work force
      emerging to capitalize on current research opportunities? The aim of this study
      was to analyze the present workforce of potential clinical investigators
      available by reviewing the mechanisms of training support as provided by the
      National Heart Lung and Blood Institute (NHLBI) and by the professional pulmonary
      societies, including their patient advocacy groups and pharmaceutical partners,
      and by discussing how support for research training might be improved for
      advanced clinical fellows. Of the approximately 500 fellows/year in a final
      training year in Pulmonary/Critical Care Medicine and related programs, about one
      third are involved mainly in supervised research and of whom about two thirds
      plan to continue fellowship training for an additional year or more
      (approximately 100-120 trainees). It seems especially important to encourage his
      particular group who are planning to extend fellowship for research training.
      Both the NHLBI and the professional pulmonary societies and their partners
      provide support for advanced fellowship trainees, but resources are limited. To
      insure that enough well-trained new clinical investigators will be available to
      conduct future pulmonary research, funding support and other career inducements
      should be discussed collectively by the NHLBI and the professional pulmonary
      societies for the purpose of optimizing support for advanced fellowship trainees.

PMID- 18633569
TI  - Long-term botulinum toxin treatment for dysphagia due to large epiphrenic
      diverticulum in elderly patients: a report of two cases.
AB  - Symptomatic esophageal epiphrenic diverticula are usually repaired with
      diverticulectomy and esophagomyotomy with substantial morbidity and mortality
      rates, especially in elderly patients. We describe the cases of two elderly
      patients who had dysphagia caused by large epiphrenic diverticula. Due to severe
      comorbid diseases, both patients were unable to withstand surgical intervention;
      botulinum toxin solution was injected endoscopically at multiple sites in the
      region of the lower esophageal sphincter and esophageal wall near the
      diverticulum. Symptoms improved immediately and the beneficial effect of
      botulinum toxin remained for 5-6 months. During the long-term follow-up, the
      patients developed symptomatic relapses treated by subsequent botulinum toxin
      solution reinjections resulting in longer-lasting symptom relief.

PMID- 18633570
TI  - Analysis of the 2004-2007 literature on therapeutic patient education in
      diabetes: results and trends.
AB  - The purpose of this study is to identify the recent characteristics and the
      developments of therapeutic education in diabetes through an analysis of the
      international articles published from 2004 to 2007. Studies were selected from
      several databases: Medline, Embase, Eric, Cochrane central database, using the
      following keywords: diabetes, patient education, self management, programs. Two
      authors independently reviewed each study and selected the data using the same
      categories of analysis. Articles consistently related to patient education in
      diabetes (80 among 118) were included. The selected articles have been published
      in 43 scientific journals. The majority of them concern TPE for adult patients
      with type 2 diabetes. TPE is delivered in several structures and education to
      groups of patients represents the most widespread educational strategy mostly
      provided by a multiprofessional team. A total of 70% of the studies show the
      effectiveness of TPE based on bioclinical, educational, psychosocial, economical
      criteria. The problem of barriers to TPE concerns 21% of the studies we have
      analysed and most of the authors propose the implementation of specifically
      designed TPE programs as strategy to overcome them. A large number of studies
      still assess the positive effects of TPE. Nowadays the problems of accessibility
      to TPE and the barriers to this practice have become a major issue for research.

PMID- 18633571
TI  - Plical resection in pre-temporal approach for basilar bifurcation aneurysms:
      preliminary surgical experience and cadaveric study.
AB  - OBJECT: Although a pre-temporal approach (PA) can provide a wide space for
      preservation of thalamoperforating atrteries in direct surgery for basilar
      bifurcation aneurysms (BBAs), it cannot always secure adequate proximal control.
      The authors described the advantages of plical resection added to PA for BBAs.
      METHODS: Between October 1998 and April 2000, eight consecutive patients with
      BBAs were treated in the neurosurgical department of Kurashiki Central Hospital.
      Among them, five patients received direct clipping using this method. There were
      four females and one male, ages ranging from 61 to 77 (mean 70.8 years). Mean
      aneurysmal size and distance between the in"terclinoidal line and the aneurysmal
      neck was 4.5 and 9.5 mm, respectively. The operative procedures consisted of the
      following components; 1) fronto-temporal craniotomy with translocation of orbito
      zygomatico-malar bone for PA, 2) preservation of lateral branches of the
      superficial sylvian veins, 3) resection of plica dural folds to increase the
      operative field up to the oculomotor nerve (OMN). RESULTS: Complete clipping was
      achieved without thalamic infarction or temporal contusion in all patients. Three
      of the five patients suffered from transient right OMN palsy which recovered
      within two months after surgery. CONCLUSION: Plical resection in the pre-temporal
      approach might be beneficial in the surgical treatment of BBAs when proximal
      control seems difficult.

PMID- 18633572
TI  - Cellular uptake of cationic gadolinium-DOTA peptide conjugates with and without N
      terminal myristoylation.
AB  - Cellular and nuclear uptake of dual labelled conjugates could be of great value
      for chemotherapy and cancer diagnostics. Therefore we designed conjugates in
      which gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      (DOTA), a contrast agent for magnetic resonance imaging and fluorescein
      isothiocyanate (FITC), a fluorescence marker were coupled to membrane
      translocation sequences (MTS). The MTSs we employed were the third helix of the
      Antennapedia homeodomain, the HIV-1 Tat peptide and the N-myristoylated HIV-1 Tat
      peptide. We used confocal laser scanning microscopy, fluorescence activated cell
      sorting, magnetic resonance imaging (MRI) and viability tests to examine the
      cellular and nuclear uptake of these conjugates into U373 glioma cells, as well
      as their cytotoxic effects. We found that the Antennapedia conjugate was taken up
      by no more than 20% of the cells. The HIV-1 Tat conjugate showed even lower
      uptake into less than 3% of cells. Interestingly, N-myristoylation of the HIV-1
      Tat conjugate drastically improved its cellular uptake. Up to 70% of cells showed
      cellular and nuclear uptake of the N-myristoylated HIV-1 Tat conjugate. Conjugate
      cytotoxicity appears to correlate with cellular uptake.

PMID- 18633573
TI  - The extremely halophilic archaeon Halobacterium salinarum R1 responds to
      potassium limitation by expression of the K+-transporting KdpFABC P-type ATPase
      and by a decrease in intracellular K+.
AB  - Halobacterium species balance high external osmolality by the accumulation of
      almost equimolar amounts of KCl. Thus, steady K(+) supply is a vital prerequisite
      for life of these extreme halophiles. So far, K(+) is reported to enter the
      halobacterial cell only passively by use of potential-driven uniporters. However,
      the genome of both the extreme halophilic archaeon Halobacterium sp. NRC-1 and H.
      salinarum R1 comprises one single gene cluster containing the genes kdpFABC
      coding for homologs of the bacterial ATP-driven K(+) uptake system KdpFABC,
      together with an additional ORF so far annotated as cat3 in Halobacterium sp. NRC
      1 and as UspA protein in H. salinarum R1 (the ORF is only referred to as cat3 in
      the following). Deletion of the kdpFABCcat3 genes led to a reduced ability to
      grow under limiting K(+) concentrations, whereas real-time RT-PCR measurements
      revealed cat3-dependent high expression rates of the Kdp system in case of
      external K(+) depletion. Synthesis of the KdpFABC complex enables H. salinarum R1
      to grow under extreme potassium-limiting conditions of >20 microM K(+). These
      results provide the first experimental evidence of an ATP-driven K(+) uptake
      system in Halobacterium. Moreover, H. salinarum R1 was shown to further adapt to
      K(+) limitation by a significant decrease of the intracellular K(+) level, which
      suggests a rather complex mechanism of K(+) homeostasis, in which the adaptation
      of cellular K(+) concentrations and the concomitant transcriptional regulation of
      genes coding for a high-affinity ATP-driven K(+) uptake system ensure the
      essential potassium supply under limiting conditions.

PMID- 18633574
TI  - Structural characterization of mutant alpha-galactosidases causing Fabry disease.
AB  - Fabry disease is an inborn error of glycolipid catabolism resulting from lesions
      in the gene encoding alpha-galactosidase (GLA). To elucidate the basis of Fabry
      disease, we constructed structural models of mutant GLAs responsible for the
      disease and calculated indexes, i.e., the numbers of atoms affected in the main
      chain and side chain of each mutant GLA, the root-mean-square distance values,
      and the solvent-accessible surface-area values, based on 212 Fabry amino acid
      substitutions previously reported (196 classic and 16 variant). As two
      therapeutic options, enzyme replacement and enzyme enhancement, are now available
      for this disease, proper prediction of the natural outcome and therapeutic
      efficiency based on the molecular evidence for individual cases are critical for
      patients' quality of life. Our results revealed that structural changes in the
      classic Fabry group were generally large and tended to be in the core region of a
      protein or located in the functionally important region, including the active
      site pocket. On the other hand, structural changes in the variant Fabry group
      were small or localized on the surface of the molecule far away from the active
      site. We focused on structural changes due to amino acid substitutions for which
      substrate analogues are effective for improving the stability or transportation
      of mutant GLAs, and the results of the study revealed that they are small or
      localized on the molecular surface, regardless of the phenotype. Coloring of
      affected atoms based on distances between wild type and mutant ones clearly
      showed the characteristic structural changes in the GLA protein geographically
      and subquantitatively. Structural investigation is useful for elucidation of the
      basis of Fabry disease and predicting disease outcome.

PMID- 18633575
TI  - Prospective study of the burden of acute gastroenteritis and rotavirus
      gastroenteritis in children less than 5 years of age, in Padova, Italy.
AB  - BACKGROUND: Data on the burden of rotavirus gastroenteritis in Europe are needed
      to help understand the potential impact of introducing new rotavirus vaccines.
      MATERIALS AND METHODS: As part of prospective observational study (Rotavirus
      gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in
      Public Health and Society Study, REVEAL) conducted in 2004--2005 in seven
      European countries, we studied, the characteristics of acute gastroenteritis and
      rotavirus gastroenteritis in children less than 5 years in primary care,
      emergency room and hospital settings (Padova, Italy). RESULTS: A total of 757
      children with acute gastroenteritis were included and enzyme-linked
      immunoabsorbent assay (ELISA) results were available for 725 cases. The overall
      estimated annual incidence for rotavirus gastroenteritis was 4.7%. Overall,
      rotavirus gastroenteritis was estimated to account for 43.6% of acute
      gastroenteritis cases. Among children with acute gastroenteritis (AGE) aged 6-23
      months, 61.2% were rotavirus positive. Rotavirus gastroenteritis (RVGE) was
      responsible for 68.8% of hospitalizations, 61% of emergency consultations, and
      33% of primary care consultations. The most prevalent serotype was G9 (84.4%)
      followed by G1 (11.8%). The relative risk for rotavirus gastroenteritis of being
      referred to hospital after an initial consultation in primary care was 3.37 (95%
      CI: 1.77-6.43) and 3.38 (95% CI: 2.28-5.01) for emergency room referral. Children
      with rotavirus gastroenteritis generally had more severe disease than children
      with rotavirus-negative gastroenteritis. CONCLUSION: Rotavirus accounts for a
      significant proportion of acute gastroenteritis cases in children less than 5
      years in Italy, many of whom require frequent primary care consultations, or care
      in emergency room or hospital settings.

PMID- 18633576
TI  - Retrospective review of adjuvant chemotherapy for esthesioneuroblastoma.
AB  - BACKGROUND: Esthesioneuroblastoma (ENB) is a rare tumor arising from the
      olfactory epithelium in the upper nasal cavity. Prior reviews have found efficacy
      of chemotherapy for high grade tumors in the advanced setting. However, little
      information is available regarding chemotherapy in the adjuvant setting. METHODS:
      A retrospective review of 76 patients treated at the Mayo Clinic for
      esthesioneuroblastoma from 1976 to 2003 was performed to evaluate adjuvant
      chemotherapy (AC) in these patients. Pathology slides were reviewed to assign
      Hyam's grade, and modified Kadish staging was available for all patients used in
      the analysis. RESULTS: Twelve patients were identified to have had full surgical
      resection of Stage C, high grade (grade 3 or 4) tumors. Six of these patients
      received AC, and six did not. Most AC was cisplatin and etoposide based. Median
      time to relapse for patients who did and did not receive AC is 35 and 10.5 months
      respectively. The median overall survival (OS) for patients that received AC was
      83+ (range 21-119+ months). The median OS for patients not receiving AC is 78
      months (range 9-240+ months). CONCLUSIONS: This small retrospective series
      suggests that adjuvant therapy for patients with high grade, Stage C
      esthesioneuroblastoma is of benefit following complete resection. Radiation
      therapy alone provides an improvement in time to relapse, which may be increased
      further with the addition of cisplatin and etoposide based chemotherapy.

PMID- 18633577
TI  - Clinicopathological study of 21 cases of eyelid actinic keratosis.
AB  - BACKGROUND: Actinic keratosis (AK) is an intraepidermal malignancy precursor form
      of cutaneous squamous cell carcinoma (SCC), which generally occurs in fair
      skinned individuals with long-term sun exposure. We present a case series of AKs
      on the eyelid. METHODS: This was a retrospective study. Data of patients seen
      from 1994 to 2005 were used in the analyses. RESULTS: There were 21 cases of
      eyelid AKs in 18 patients, 11 men, and seven women, with a mean age of 70 (range
      43-80) years. Most tumors were located on the upper eyelid. The mean size was 0.8
      +/- 0.4 cm. The most frequent AK type was type I (76.2%). Men had bigger lesions
      and more frequent free-margin eyelid involvement. CONCLUSIONS: In our series,
      tumors were more frequent and had worse clinical and histopathological features
      in men. AKs are closely related to SCC and need to be removed before they turn
      into SCC. They can be safely and effectively removed, and therapy is therefore
      warranted.

PMID- 18633578
TI  - Isolation of cross-reacting antigen candidates by mRNA-display using a mixed cDNA
      library.
AB  - The identification of cross-reacting antigens is an important process in the
      characterization of antibodies. We describe here the application of mRNA-display
      technology with a cDNA library for the isolation of cross-reacting antigens using
      a monoclonal antibody against human tumor protein p53 (hTP53) as a model. A mixed
      cDNA library constructed from mRNAs prepared from several human tissues and cell
      lines was used for the mRNA-display. After several rounds of panning, five
      annotated polypeptides, topoisomeraseII-binding protein 1 (TOBP1), RAS protein
      activator like 2 isoform 1 (RASAL2), endosome-associated FYVE-domain protein
      (ZFYVE16), and utrophin (UTRN) as well as hTP53, were identified as cross
      reactive antigen candidates. All of them had a consensus motif, -S-D-L-( )-K-L-,
      which was included in the known epitope of the antibody. They were synthesized in
      vitro, and their binding was compared by conducting a pull-down assay. In cross
      activity to the antibody, they ranked as follows: ZYVE16 congruent with hTP53
      congruent with TOBP1 > UTRN > RASAL2.

PMID- 18633579
TI  - [Historic perspective and the work of Pointner and Granderath in hiatus hernia
      and recurrence].

PMID- 18633580
TI  - Extremely high frequency electromagnetic radiation enforces bacterial effects of
      inhibitors and antibiotics.
AB  - The coherent electromagnetic radiation (EMR) of the frequency of 51.8 and 53 GHz
      with low intensity (the power flux density of 0.06 mW/cm(2)) affected the growth
      of Escherichia coli K12(lambda) under fermentation conditions: the lowering of
      the growth specific rate was considerably (approximately 2-fold) increased with
      exposure duration of 30-60 min; a significant decrease in the number of viable
      cells was also shown. Moreover, the enforced effects of the N,N'
      dicyclohexylcarbodiimide (DCCD), inhibitor of H(+)-transporting F(0)F(1)-ATPase,
      on energy-dependent H(+) efflux by whole cells and of antibiotics like
      tetracycline and chloramphenicol on the following bacterial growth and survival
      were also determined after radiation. In addition, the lowering in DCCD-inhibited
      ATPase activity of membrane vesicles from exposed cells was defined. The results
      confirmed the input of membranous changes in bacterial action of low intensity
      extremely high frequency EMR, when the F(0)F(1)-ATPase is probably playing a key
      role. The radiation of bacteria might lead to changed metabolic pathways and to
      antibiotic resistance. It may also give bacteria with a specific role in
      biosphere.

PMID- 18633582
TI  - [Therapy of cardiogenic shock after myocardial infarction].
AB  - The therapy of infarct related cardiogenic shock should primarily focus on
      fastest possible revascularization. In addition, rapid restoration of sufficient
      organ perfusion pressure is recommended for the prevention of a multi-organ
      dysfunction syndrome (MODS). This can be achieved by mechanical circulatory
      assist devices as well as individual catecholamine therapy. Since assist devices
      require specially trained physicians, their use is limited to specialized cardiac
      care centers. However, future technologies such as portable heart-lung-machines
      may help to further improve transfer to specialized centers and therapy of shock
      patients.

PMID- 18633583
TI  - Mushroom harvesting ants in the tropical rain forest.
AB  - Ants belong to the most important groups of arthropods, inhabiting and commonly
      dominating most terrestrial habitats, especially tropical rainforests. Their
      highly collective behavior enables exploitation of various resources and is
      viewed as a key factor for their evolutionary success. Accordingly, a great
      variety of life strategies evolved in this group of arthropods, including seed
      harvesters, gardeners, and planters, fungus growers, nomadic hunters, life stock
      keepers, and slave makers. This study reports the discovery of a new lifestyle in
      ants. In a Southeast Asian rainforest habitat, Euprenolepis procera is
      specialized in harvesting a broad spectrum of naturally growing mushrooms, a
      nutritionally challenging and spatiotemporally unpredictable food source. While
      unfavorable to the vast majority of animals, E. procera has developed exceptional
      adaptations such as a shift to a fully nomadic lifestyle and special food
      processing capabilities, which allow it to rely entirely on mushrooms. As a
      consequence, E. procera is the most efficient and predominant consumer of epigeic
      mushrooms in the studied habitat and this has broad implications for the tropical
      rainforest ecosystem.

PMID- 18633584
TI  - Order parameters from image analysis: a honeycomb example.
AB  - Honeybee combs have aroused interest in the ability of honeybees to form regular
      hexagonal geometric constructs since ancient times. Here we use a real space
      technique based on the pair distribution function (PDF) and radial distribution
      function (RDF), and a reciprocal space method utilizing the Debye-Waller Factor
      (DWF) to quantify the order for a range of honeycombs made by Apis mellifera
      ligustica. The PDFs and RDFs are fit with a series of Gaussian curves. We
      characterize the order in the honeycomb using a real space order parameter, OP (
      3 ), to describe the order in the combs and a two-dimensional Fourier transform
      from which a Debye-Waller order parameter, u, is derived. Both OP ( 3 ) and u
      take values from [0, 1] where the value one represents perfect order. The
      analyzed combs have values of OP ( 3 ) from 0.33 to 0.60 and values of u from
      0.59 to 0.69. RDF fits of honeycomb histograms show that naturally made comb can
      be crystalline in a 2D ordered structural sense, yet is more 'liquid-like' than
      cells made on 'foundation' wax. We show that with the assistance of man-made
      foundation wax, honeybees can manufacture highly ordered arrays of hexagonal
      cells. This is the first description of honeycomb utilizing the Debye-Waller
      Factor, and provides a complete analysis of the order in comb from a real-space
      order parameter and a reciprocal space order parameter. It is noted that the
      techniques used are general in nature and could be applied to any digital
      photograph of an ordered array.

PMID- 18633585
TI  - [Ethical questions in clinical research with the mentally ill].
AB  - The review deals with present problems of protecting mentally ill patients who
      are incompetent to give informed consent to participating in clinical research,
      and of assessment of the capacity to consent. 1. Clinical trials of drugs on
      efficacy and safety in incompetent patients are ethically justified and legally
      admissible if the investigational drug can be expected to exert a direct
      potential individual benefit and if such trials will be performed under defined
      criteria to protect these vulnerable patients. In Germany it is questionable how
      far these prescriptions of the German Drug Law (AMG) are transferable to other
      than drug research. 2. Research with no direct potential individual benefit or
      only a group-specific benefit in incompetent patients is controversially
      discussed. However, it may be ethically justified as an exception, and is in
      Germany legally admissible only in minors, but not in adults. 3. However,
      internationally there exists a wide range of legal regulations, terms,
      interpretations, and practices of research with vulnerable persons. In the past
      years a shift seems to have developed from normatively oriented discussions to
      more empirically based investigations. Especially vague but clinically relevant
      terms in protection declarations or guidelines have been better specified, put in
      concrete form by anchor examples, and empirically studied. 4. In general the
      criteria of protecting the dignity and, even if impaired, the autonomy of
      incompetent patients as subjects for research appear to guarantee a high standard
      of protection. However, the application of these criteria must be improved by
      practicable procedures. This is valid particularly for the assessment of the
      basic criterion whether a patient is capable of consenting or not. 5. Open
      Questions are formulated as need of research.

PMID- 18633586
TI  - [Pharmacotherapy of central oculomotor disorders].
AB  - Nystagmus causes blurred vision due to oscillopsia, as well as impaired balance.
      Depending on etiology, additional cerebellar and brain stem signs may occur. We
      present the current pharmacotherapy of the most common forms of central
      nystagmus: downbeat nystagmus (DBN), upbeat nystagmus (UBN), acquired pendular
      nystagmus (APN), and congenital nystagmus (CGN). Recommended medical therapies
      are aminopyridines (4-AP) for DBN and UBN, gabapentin and memantine for CGN and
      APN, and baclofen for periodic alternating nystagmus (PAN).

PMID- 18633587
TI  - [Zonisamide as add-on treatment for focal epilepsies. An outcome analysis of 74
      patients].
AB  - BACKGROUND: Evaluation of efficacy and tolerability of zonisamide (ZNS) used as
      an add-on treatment in patients with chronic focal epilepsies. MATERIAL AND
      METHODS: Retrospective data analysis in 74 patients (38 men, 36 women), age 17-61
      years (mean 35 years). Duration of epilepsy was 2-50 years (mean 23.3 years).
      Additional antiepileptic drugs 2-5 (mean 2.7). RESULTS: The ZNS daily dosage
      varied between 100 mg and 500 mg (mean 368 mg). Seizure frequency could be
      estimated in 50 patients; it decreased by at least 50% in 11 patients (22%),
      remained unchanged in 28 patients (56%), and increased by at least 50% in 11
      patients (22%). None of the patients achieved complete seizure control. Side
      effects were seen in 45/74 patients (60.8%). Adverse events resulting in
      discontinuation of treatment with ZNS were documented in 24 patients (32.4%). Out
      of 70 patients, 34 (48.5%) remained on ZNS 12 months after the onset of therapy.
      CONCLUSIONS: In this study, ZNS proved to be an antiepileptic drug with a
      comparatively low anticonvulsant efficacy as an add-on treatment in patients with
      chronic focal epilepsies.

PMID- 18633589
TI  - [Benign neuroendocrine and other rare benign tumors of the pancreas].
AB  - Neuroendocrine tumors (NET) of the pancreas are rare neoplasms, which arise from
      cells of the islets of Langerhans. The most common NET are the insulinoma,
      gastrinoma and hormone inactive NET. Very rare entities are the schwannoma,
      leiomyoma, teratoma, intrapancreatic lipoma, hemangioma and the intrapancreatic
      accessory spleen. Essential for therapy, which in most cases is difficult, are an
      exact localization and various modalities of imaging diagnostics.

PMID- 18633590
TI  - Genetic diversity among oat varieties of worldwide origin and associations of
      AFLP markers with quantitative traits.
AB  - One hundred and fourteen oat (Avena sativa L.) varieties of worldwide origin were
      evaluated for genetic diversity based on 77 molecular polymorphisms produced by
      eight selective AFLP primer combinations. Genetic similarity, calculated using
      the DICE coefficient, was used for cluster analysis and principal component
      analysis was applied. In addition population structure was explored to identify
      discrete subpopulations based on allele frequency. Although clustering and
      population structure showed relationships with region and country of origin,
      there was no obvious relationship to hull presence or hull colour. Oat varieties
      originating from European breeding programs showed less diversity than varieties
      originating from North and South America. Associations between AFLP markers and
      agronomic traits (grain yield, groat yield, panicle emergence, plant height, and
      lodging) as well as kernel quality traits (kernel weight, test weight, screening
      percent and groat percent) were also investigated. Marker-trait associations were
      tested using a naive simple regression model and five additional models that
      account for population structure. Significant associations were found for 23 AFLP
      markers, with many of these affecting multiple traits. This study demonstrates
      that diversity can be significantly enhanced using a global collection, and
      provides evidence for marker-trait associations that can be validated in
      segregating populations and exploited through marker-assisted selection.

PMID- 18633592
TI  - High throughput genome-specific and gene-specific molecular markers for erucic
      acid genes in Brassica napus (L.) for marker-assisted selection in plant
      breeding.
AB  - A single base change in the Bn-FAE1.1 gene in the A genome and a two-base
      deletion in the Bn-FAE1.2 gene in the C genome produce the nearly zero content of
      erucic acid observed in canola. A BAC clone anchoring Bn-FAE1.1 from a B. rapa
      BAC library and a BAC clone anchoring Bn-FAE1.2 from a B. oleracea BAC library
      were used in this research. After sequencing the gene flanking regions, it was
      found that the dissimilarity of the flanking sequences of these two FAE1 homologs
      facilitated the design of genome-specific primers that could amplify the
      corresponding genome in allotetraploid B. napus. The two-base deletion in the C
      genome gene was detected as a sequence-characterized amplified region (SCAR)
      marker. To increase the throughput, one genome-specific primer was labeled with
      four fluorescence dyes and combined with 20 different primers to produce PCR
      products with different fragment sizes. Eventually, a super pool of 80 samples
      was detected simultaneously. This dramatically reduces the cost of marker
      detection. The single base change in the Bn-FAE1.1 gene was detected as single
      nucleotide polymorphic (SNP) marker with an ABI SNaPshot kit. A multiplexing
      primer set was designed by adding a polyT to the 5' primer end to increase SNP
      detection throughput through sample pooling. Furthermore, the Bn-FAE1.1 and Bn
      FAE1.2 were integrated into the N8 and N13 linkage groups of our previously
      reported high-density sequence-related amplified polymorphism (SRAP) map,
      respectively. There were 124 SRAP markers in a N8 bin in which the Bn-FAE1.1 gene
      specific SCAR marker was located and 46 SRAP markers in a N13 bin into which the
      Bn-FAE1.2 SNP marker was integrated. These three kinds of high throughput
      molecular markers have been successfully implemented in our canola/rapeseed
      breeding programs.

PMID- 18633591
TI  - SSRs and INDELs mined from the sunflower EST database: abundance, polymorphisms,
      and cross-taxa utility.
AB  - Simple sequence repeats (SSRs) are abundant and frequently highly polymorphic in
      transcribed sequences and widely targeted for marker development in eukaryotes.
      Sunflower (Helianthus annuus) transcript assemblies were built and mined to
      identify SSRs and insertions-deletions (INDELs) for marker development,
      comparative mapping, and other genomics applications in sunflower. We describe
      the spectrum and frequency of SSRs identified in the sunflower EST database, a
      catalog of 16,643 EST-SSRs, a collection of 484 EST-SSR and 43 EST-INDEL markers
      developed from common sunflower ESTs, polymorphisms of the markers among the
      parents of several intraspecific and interspecific mapping populations, and the
      transferability of the markers to closely and distantly related species in the
      Compositae. Of 17,904 unigenes in the transcript assembly, 1,956 (10.9%) harbored
      one or more SSRs with repeat counts of n > or = 5. EST-SSR markers were 1.6-fold
      more polymorphic among exotic than elite genotypes and 0.7-fold less polymorphic
      than non-genic SSR markers. Of 466 EST-SSR or INDEL markers screened for cross
      species amplification and polymorphisms, 413 (88.6%) amplified alleles from one
      or more wild species (H. argophyllus, H. tuberosus, H. anomalus, H. paradoxus,
      and H. deserticola), whereas 69 (14.8%) amplified alleles from safflower
      (Carthamus tinctorius) and 67 (14.4%) amplified alleles from lettuce (Lactuca
      sativa); hence, only a fraction were transferable to distantly related genera in
      the Compositae, whereas most were transferable to wild relatives of H. annuus.
      Several thousand additional SSRs were identified in the EST database and supply a
      wealth of templates for EST-SSR marker development in sunflower.

PMID- 18633593
TI  - Performance of the revised '175' Modification of Diet in Renal Disease equation
      in patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Estimation of GFR (eGFR) is recommended for the assessment of
      kidney function in all patients with diabetes. We studied performance of the
      traditional '186' Modification of Diet in Renal Disease (MDRD) equation, and the
      2005 revised '175' MDRD equation in patients with type 2 diabetes. METHODS: Two
      hundred and ninety-three mainly normoalbuminuric (267/293) patients were
      recruited. Patients were classified as having mild renal impairment (group 1, GFR
      <90 ml min(-1) 1.73 m(-2)) or normal renal function (group 2, GFR >or=90 ml min(
      1) 1.73 m(-2)). eGFR was calculated by the traditional 186 MDRD equation using
      traditional creatinine values and the revised 175 MDRD equation using isotope
      dilution mass spectrometry-standardised creatinine values. Isotopic GFR was
      measured by the four-sample plasma clearance of (51)Cr-EDTA. RESULTS: For
      patients in group 1, mean +/- SD isotopic (51)Cr-EDTA GFR (iGFR) was 83.8 +/- 4.3
      ml min(-1) 1.73 m(-2), and eGFR was 73.2 +/- 11.9 and 75.8 +/- 13.7 ml min(-1)
      1.73 m(-2) using the 186 and 175 MDRD equations, respectively. Method bias was 
      10.6 with the 186 MDRD and -7.9 ml min(-1) 1.73 m(-2) (p < 0.05) with the 175
      MDRD equation. In group 2, iGFR was 119.4 +/- 20.2 ml min(-1) 1.73 m(-2), and
      eGFR was 92.3 +/- 18.6 and 97.5 +/- 21.6 ml min(-1) 1.73 m(-2) using the 186 and
      175 MDRD equations, respectively. Method bias was -27.1 with the 186 MDRD
      equation and -21.9 ml min(-1) 1.73 m(-2) (p < 0.05) with the 175 MDRD equation.
      CONCLUSIONS/INTERPRETATION: In patients newly diagnosed with type 2 diabetes, the
      revised 175 MDRD equation was less biased than the traditional 186 MDRD equation.
      Despite a continued tendency to underestimate isotopically measured GFR, use of
      standardised creatinine values is a positive step towards improved estimation of
      GFR.

PMID- 18633594
TI  - Molecular composition of the peri-islet basement membrane in NOD mice: a barrier
      against destructive insulitis.
AB  - AIMS/HYPOTHESIS: This study examined whether the capsule which encases islets of
      Langerhans in the NOD mouse pancreas represents a specialised extracellular
      matrix (ECM) or basement membrane that protects islets from autoimmune attack.
      METHODS: Immunofluorescence microscopy using a panel of antibodies to collagens
      type IV, laminins, nidogens and perlecan was performed to localise matrix
      components in NOD mouse pancreas before diabetes onset, at onset of diabetes and
      after clinical diabetes was established (2-8.5 weeks post-onset). RESULTS:
      Perlecan, a heparan sulphate proteoglycan that is characteristic of basement
      membranes and has not previously been investigated in islets, was localised in
      the peri-islet capsule and surrounding intra-islet capillaries. Other components
      present in the peri-islet capsule included laminin chains alpha2, beta1 and
      gamma1, collagen type IV alpha1 and alpha2, and nidogen 1 and 2. Collagen type IV
      alpha3-alpha6 were not detected. These findings confirm that the peri-islet
      capsule represents a specialised ECM or conventional basement membrane. The islet
      basement membrane was destroyed in islets where intra-islet infiltration of
      leucocytes marked the progression from non-destructive to destructive insulitis.
      No changes in basement membrane composition were observed before leucocyte
      infiltration. CONCLUSIONS/INTERPRETATION: These findings suggest that the islet
      basement membrane functions as a physical barrier to leucocyte migration into
      islets and that degradation of the islet basement membrane marks the onset of
      destructive autoimmune insulitis and diabetes development in NOD mice. The
      components of the islet basement membrane that we identified predict that
      specialised degradative enzymes are likely to function in autoimmune islet
      damage.

PMID- 18633595
TI  - Airway pressure release ventilation and biphasic positive airway pressure: a
      systematic review of definitional criteria.
AB  - OBJECTIVE: The objective of this study was to identify the definitional criteria
      for the pressure-limited and time-cycled modes: airway pressure release
      ventilation (APRV) and biphasic positive airway pressure (BIPAP) available in the
      published literature. DESIGN: Systematic review. METHODS: Medline, PubMed,
      Cochrane, and CINAHL databases (1982-2006) were searched using the following
      terms: APRV, BIPAP, Bilevel and lung protective strategy, individually and in
      combination. Two independent reviewers determined the paper eligibility and
      abstracted data from 50 studies and 18 discussion articles. MEASUREMENTS AND
      RESULTS: Of the 50 studies, 39 (78%) described APRV, and 11 (22%) described
      BIPAP. Various study designs, populations, or outcome measures were investigated.
      Compared to BIPAP, APRV was described more frequently as extreme inverse
      inspiratory:expiratory ratio [18/39 (46%) vs. 0/11 (0%), P = 0.004] and used
      rarely as a noninverse ratio [2/39 (5%) vs. 3/11 (27%), P = 0.06]. One (9%) BIPAP
      and eight (21%) APRV studies used mild inverse ratio (>1:1 to < or =2:1) (P =
      0.7), plus there was increased use of 1:1 ratio [7 (64%) vs. 12 (31%), P = 0.08]
      with BIPAP. In adult studies, the mean reported set inspiratory pressure (PHigh)
      was 6 cm H2O greater with APRV when compared to reports of BIPAP (P = 0.3). For
      both modes, the mean reported positive end expiratory pressure (PLow) was 5.5 cm
      H2O. Thematic review identified inconsistency of mode descriptions. CONCLUSIONS:
      Ambiguity exists in the criteria that distinguish APRV and BIPAP. Commercial
      ventilator branding may further add to confusion. Generic naming of modes and
      consistent definitional parameters may improve consistency of patient response
      for a given mode and assist with clinical implementation.

PMID- 18633597
TI  - Minimal invasive and computer assisted total knee replacement compared with the
      conventional technique: a prospective, randomised trial.
AB  - Minimal invasive surgery (MIS) in total knee replacement (TKR) has been favoured
      by several authors and the industry and is asked for by the patients. Computer
      assisted surgery (CAS) is proposed to support the surgeon in terms of
      postoperative leg alignment and implant orientation. To prove the hypothesis that
      MIS in TKR fastens early rehabilitation compared to the standard approach and
      that CAS-MIS in TKR improves accuracy in implant position compared to the
      freehand MIS and freehand standard technique, we performed a prospective,
      randomised short-term trial which was approved by the local ethic committee. In
      total, 90 patients underwent TKR. The conventional group (n = 30) underwent
      conventional TKR, the MIS group (n = 30) underwent MIS-TKR without navigation,
      the CAS-MIS group (n = 30) underwent TKR using navigation and the MIS approach.
      Groups were comparable regarding patients' specific parameters. The length of
      incision in extension was significantly lower in the MIS (13.2 cm) and CAS-MIS
      technique (12.9 cm) compared to the conventional technique (17.3 cm) (P < 0.01).
      Knee Society and WOMAC Score were similar in all three groups after 1, 6 and 12
      weeks, no significant differences were seen between groups at any point of time.
      Postoperative deviation of the mechanical leg axis was significantly better in
      the CAS-MIS group compared to the conventional group and the MIS one (P < 0.05).
      The clinical relevance of our results is that the benefit of the minimal invasive
      approach in TKR is still not proven and navigation improves postoperative
      accuracy of leg alignment and component orientation. Our study shows that for the
      group of patients included there is no statistically significant difference in
      early rehabilitation between MIS and the conventional approach based on the Knee
      Society and WOMAC Score. Using the CAS technique restoration of leg axis was more
      accurate.

PMID- 18633598
TI  - Arthroscopic all-inside repair for a tear of posterior root of the medial
      meniscus: a technical note.
AB  - This technical note describes a new arthroscopic technique to repair a tear of
      posterior root of the medial meniscus. Cartilage at the insertion area of the
      posterior horn of the medial meniscus (PHMM) was removed using a curved curette
      inserted through an anteromedial portal. A metal anchor loaded with two
      FiberWires (Arthrex, Naples, FL) was placed at the insertion area of the PHMM
      through a high posteromedial portal. A PDS suture was passed the PHMM by curved
      suture hook through the anteromedial portal. Two limbs of the PDS were then used
      to pass two limbs of the FiberWire through the meniscus. The same procedure was
      repeated for the second FiberWire suture. The sutures were tied, achieving secure
      fixation of the posterior meniscal root at the anatomic insertion.

PMID- 18633596
TI  - Graft healing in anterior cruciate ligament reconstruction.
AB  - Graft healing within the bone tunnel after anterior cruciate ligament (ACL)
      reconstruction is still a complex, poorly understood biological process that is
      influenced by multiple surgical and postoperative variables. However, remarkable
      advances in knowledge of this process have been made based primarly on animal
      models. According to the findings of this review, some surgical and postoperative
      variables are known to directly affect time-course and quality of graft-tunnel
      healing. The type of graft, graft motion, and fixation methods have shown to
      directly affect time-course and quality of graft-tunnel healing. Therefore, the
      application of early and aggressive rehabilitation protocols should be cautious
      when using soft-tissue graft, allografts, and direct or aperture type of fixation
      for ACL reconstruction. With regard to graft placement, several cadaveric models
      showed biomechanical advantages of a more anatomical graft location; however,
      there are no studies that explore the relationship between graft placement and
      healing process. The precise effect of graft tensioning, graft/tunnel diameter
      disparity, and graft length within the bone tunnel in the graft healing process
      remains unclear and requires more research. To enhance graft-tunnel healing,
      tissue-engineering approaches, including the use of growth factors, mesenchymal
      stem cells, and periosteum graft augmentation, have been tested on animal models.
      These have shown promising results in terms of enhancement of bone-graft healing
      rate.

PMID- 18633599
TI  - Sclerosing injections to treat midportion Achilles tendinosis: a randomised
      controlled study evaluating two different concentrations of Polidocanol.
AB  - Two to three ultrasound (US) and colour Doppler (CD)-guided injections of the
      sclerosing substance Polidocanol (5 mg/ml) have been demonstrated to give good
      clinical results in patients with chronic midportion Achilles tendinopathy. This
      study aimed to investigate if a higher concentration of Polidocanol (10 mg/ml)
      would lead to a less number of treatments, and lower volumes, needed for good
      clinical results. Fifty-two consecutive Achilles tendons (48 patients, mean age
      49.6 years) with chronic painful midportion Achilles tendinopathy, were
      randomised to treatment with Polidocanol 5 mg/ml (group A) or 10 mg/ml (group B).
      The patients and treating physician were blinded to the concentration of
      Polidocanol injected. All patients had structural tendon changes and
      neovascularisation in the Achilles midportion. Treatment was US + CD-guided
      injections targeting the region with neovascularisation (outside ventral tendon).
      A maximum of three treatments (6-8 weeks in between) were given before
      evaluation. Patients not satisfied after three treatments were given additional
      treatment with Polidocanol 10 mg/ml, up to five treatments. For evaluation, the
      patients recorded the severity of Achilles tendon pain during activity on a
      visual analogue scale (VAS), before and after treatment. Patient satisfaction
      with treatment was also assessed. At follow-up (mean 14 months) after three
      treatments, 18/26 patients in group A and 19/26 patients in group B were
      satisfied with the treatment and had a significantly reduced level of tendon pain
      (P < 0.05). After completion of the study, additional treatments with Polidocanol
      10 mg/ml in the not satisfied patients resulted in 26/26 satisfied patients in
      both groups A and B. In summary, we found no significant differences in the
      number of satisfied patients, number of injections or volumes given, between
      patients treated with 5 or 10 mg/ml Polidocanol.

PMID- 18633600
TI  - Diazinon oxon affects the differentiation of mouse N2a neuroblastoma cells.
AB  - The aim of this study was to assess the neurotoxicity of diazinon oxon (DZO), a
      major in vivo metabolite of the phosphorothionate insecticide diazinon (DZ), on
      differentiating mouse N2a neuroblastoma cells. When used at concentrations of 1,
      5 and 10 microM, DZO did not cause cell death but it impaired the outgrowth of
      axon-like processes after 24 h. Densitometric scanning of Western blots of
      lysates of N2a cells revealed that exposure to 5 or 10 microM DZO for 24 h
      increased the expression of phosphorylated neurofilament heavy chain (NFH)
      compared to controls, while there was no significant change in total NFH. By
      contrast, treatment of N2a cells with 1-10 microM DZO resulted in marked
      reductions in the expression of the axon growth-associated protein GAP-43. DZO
      treated cells also showed an increased expression of the heat shock protein HSP
      70 compared to controls. The above biochemical changes were not temporally
      related to inhibition of acetylcholinesterase (AChE). These data suggest that
      biologically relevant, subcytotoxic levels of DZO may exert neurotoxic effects on
      differentiating cells and that the mechanisms involved are different from those
      attributed to its parent compound.

PMID- 18633602
TI  - Solution to isotopic abundance challenge.

PMID- 18633601
TI  - Reference-dose place conditioning with ethanol in mice: empirical and theoretical
      analysis.
AB  - RATIONALE: A frequently expressed criticism of the conditioned place preference
      (CPP) procedure is that it sometimes lacks a graded dose-response curve for many
      drugs. OBJECTIVE: We used a combination of standard and reference-dose CPP
      procedures to examine the dose-response curve for ethanol-induced CPP in DBA/2J
      mice. MATERIALS AND METHODS: In the standard procedure, ethanol (0.5, 1.5, 2, and
      4 g/kg) was paired with a distinctive floor cue, whereas saline was paired with a
      different floor cue. In the reference-dose procedure, each cue was paired with a
      different dose of ethanol. All mice received four 5-min trials of each type in
      both procedures. RESULTS: Standard procedures yielded similar levels of CPP at
      doses of 1.5, 2, and 4 g/kg, whereas 0.5 g/kg did not produce significant CPP.
      However, in the reference-dose procedure, exposure to the 0.5-g/kg dose
      interfered with CPP normally produced by 1.5 or 2 g/kg. Moreover, mice showed
      significant preference for the 4-g/kg-paired cue over the 1.5-g/kg-paired cue.
      CONCLUSIONS: These studies show that a reference-dose procedure can reveal
      effects of low doses that are sometimes difficult to detect in a standard
      procedure. The reference-dose procedure may also uncover differences between
      higher doses that normally produce similar preference. Efficacy of the reference
      dose procedure may be explained by a theoretical analysis that assumes the
      procedure places behavior between the extremes of the performance range, offering
      a more sensitive method for detecting effects of manipulations that produce small
      changes and/or differences in the rewarding effects of ethanol.

PMID- 18633603
TI  - Cytochromes P450, induction and cholesterol--what are the connections?

PMID- 18633605
TI  - Acute renal failure due to bilateral ureteral stone impaction in an HIV-positive
      patient.
AB  - A 51-year-old HIV-positive man treated with atazanavir for 9 months presented
      with anuria following right flank pain. Laboratory examination indicated renal
      insufficiency, and abdominopelvic computed tomography scanning showed bilateral
      hydroureteronephrosis, but no stones were visualized. Endoscopic procedures were
      performed to investigate the causes of ureteral obstruction and, if possible, to
      insert Double-J stents in the ureters. A yellowish stone composed of pure
      atazanavir was found at the right ureteral orifice, and retrograde pyelography
      revealed a filling defect in the left ureter found to be caused by an atazanavir
      stone. The patient's renal function recovered after removal of these stones.

PMID- 18633606
TI  - Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric
      postmenopausal osteoporosis.
AB  - Hypercalciuria of intestinal origin has been linked with bone loss in calcium
      nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was
      performed to explore potential pathogenetic link between intestinal
      hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved
      from postmenopausal women who were evaluated for osteoporosis or osteopenia at
      the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319
      patients underwent the test of calciuric response to oral calcium load to obtain
      an indirect measure of intestinal calcium absorption. Serum and urinary
      biochemistry and L2-L4 bone mineral density (BMD) were compared between five
      quintiles of calciuric response. There was a statistically significant trend
      toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline
      (DPD) and BMD, with increasing order of quintiles. The presentation of those in
      the 1st quintile was consistent with vitamin D insufficiency or deficiency, with
      impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone
      turnover (high normal urinary DPD). In contrast, patients in the 5th quintile
      displayed a picture of absorptive hypercalciuria of stone disease, with
      intestinal hyperabsorption of calcium, high or high normal urinary calcium and
      suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of
      intestinal calcium absorption in a seemingly homogeneous group of postmenopausal
      women with osteoporosis or osteopenia revealed a spectrum of calciuric response
      whose extremes may represent two physiologically distinct subtypes that have
      important diagnostic and therapeutic implications.

PMID- 18633604
TI  - Cytochrome P450 and gene activation--from pharmacology to cholesterol elimination
      and regression of atherosclerosis.
AB  - BACKGROUND: Lipoproteins are closely associated with the atherosclerotic vascular
      process. Elevated levels of high-density lipoprotein cholesterol (HDL-C) and
      apolipoprotein AI (apo AI) in plasma indicate a low probability of coronary heart
      disease (CHD) together with enhanced longevity, and elevated levels of low
      density lipoprotein-cholesterol (LDL-C) and apo B indicate an increased risk of
      CHD and death. Studies linking gene activation and the induction of cytochrome
      P450 with elevated plasma levels of apo AI and HDL-C and lowered plasma levels of
      LDL-C presented a new potential approach to prevent and treat atherosclerotic
      disease. OBJECTIVE AND METHODS: This is a review aimed at clarifying the effects
      of P450-enzymes and gene activation on cholesterol homeostasis, the
      atherosclerotic vascular process, prevention and regression of atherosclerosis
      and the manifestation of atherosclerotic disease, particularly CHD, the leading
      cause of death in the world. RESULTS: P450-enzymes maintain cellular cholesterol
      homeostasis. They respond to cholesterol accumulation by enhancing the generation
      of hydroxycholesterols (oxysterols) and activating cholesterol-eliminating
      mechanisms. The CYP7A1, CYP27A1, CYP46A1 and CYP3A4 enzymes generate major
      oxysterols that enter the circulation. The oxysterols activate-via nuclear
      receptors-ATP-binding cassette (ABC) A1 and other genes, leading to the
      elimination of excess cholesterol and protecting arteries from atherosclerosis.
      Several drugs and nonpharmacologic compounds are ligands for the liver X
      receptor, pregnane X receptor and other receptors, activate P450 and other genes
      involved in cholesterol elimination, prevent or regress atherosclerosis and
      reduce cardiovascular events. CONCLUSIONS: P450-enzymes are essential in the
      physiological maintenance of cholesterol balance. They activate mechanisms which
      eliminate excess cholesterol and counteract the atherosclerotic process. Several
      drugs and nonpharmacologic compounds induce P450 and other genes, prevent or
      regress atherosclerosis and reduce the occurrence of non-fatal and fatal CHD and
      other atherosclerotic diseases.

PMID- 18633607
TI  - Renal pyramid echogenicity in ureteropelvic junction obstruction: correlation
      between altered echogenicity and differential renal function.
AB  - BACKGROUND: Improvement in resolution and use of high-frequency transducers in US
      has enabled visualization of previously unreported changes in medullary pyramid
      echogenicity in children with obstructive hydronephrosis. OBJECTIVE: To determine
      whether these unreported changes in echogenicity and morphology of the renal
      pyramids in ureteropelvic junction (UPJ) obstruction correlate with differential
      renal function (DRF) of the kidney as determined by technetium-99m
      mercaptoacetyltriglycine ((99m)Tc-MAG3) scan. MATERIALS AND METHODS: Renal
      sonograms in 60 children with UPJ obstruction were retrospectively reviewed.
      Children were divided into three groups based on the echogenicity of the
      pyramids: (1) normal echogenicity of the pyramids, (2) increased echogenicity of
      the pyramids with maintained corticomedullary differentiation (CMD), and (3) loss
      of CMD. DRF, as determined by (99m)Tc-MAG3 scan, of the obstructed kidney of > or
      =45% was considered normal and of < or =44% was considered abnormal based on a
      published study correlating histological changes with DRF. Fisher's exact test
      was performed for assessing the association between DRF and altered echogenicity
      of the pyramids. RESULTS: In group 1, which consisted of 13 patients with normal
      pyramids on US, DRF was normal in 11 and abnormal in two. In group 2, which
      consisted of 33 patients with echogenic pyramids and preserved CMD, DRF was
      normal in 15 and abnormal in 18. In group 3, which consisted of 14 patients with
      complete loss of CMD, DRF was normal in 2 and abnormal in 12. There was a strong
      correlation between abnormal pyramids and DRF (P=0.0009). The risk ratio (RR) of
      DRF becoming abnormal for those kidneys with abnormal echogenicity of the
      pyramids with preserved CMD (group 2) compared to normal pyramid echogenicity
      (group 1) was 1.56 (95% CI 1.088-2.236). The RR of DRF becoming abnormal for
      those kidneys with loss of CMD (group 3) compared to normal pyramid echogenicity
      (group 1) was 5.571 (95% CI 1.530-20.294). CONCLUSION: We observed that in
      obstructed kidneys the echogenicity of the pyramids may be abnormal. Increased
      echogenicity of the pyramids correlated weakly with abnormal DRF and does not
      necessarily indicate poor renal function. However, loss of CMD strongly
      correlated with poor renal function.

PMID- 18633608
TI  - MRI of the fetal eyes: morphologic and biometric assessment for abnormal
      development with ultrasonographic and clinicopathologic correlation.
AB  - BACKGROUND: Currently ocular biometric measurements are defined by US and are
      measured from the orbital walls. These bony landmarks cannot be seen by MRI, and
      therefore these measurements cannot be directly applied. OBJECTIVE: To define
      measurements of normal growth of the fetal eyes using MRI. MATERIALS AND METHODS:
      Transorbital views were analyzed in 198 fetal MR examinations. The ocular
      diameter (OD) and interocular and binocular distances (IOD and BOD) were measured
      and were plotted against gestational age. Fetuses with abnormalities affecting
      the eyes were evaluated separately. RESULTS: Of 198 scans, 146 had suitable
      images, 35 of which were abnormal. Normal growth of BOD, IOD and OD were
      determined, and compared with the respective already established US data.
      CONCLUSION: Normal growth charts were derived from a cohort of 111 normal
      fetuses. Because the margins of the vitreous are inside the bony orbit, at the
      same gestational age measurements of the BOD and OD are always less than the
      corresponding measurements by US, and those of the IOD are always more. Normal
      growth charts for MRI can now be used to support suspected diagnoses of orbital
      and ocular pathologies and the syndromes that give rise to them, and many
      examples are demonstrated.

PMID- 18633609
TI  - Characterization of an alpha-L-rhamnosidase from Aspergillus kawachii and its
      gene.
AB  - An alpha-L-rhamnosidase was purified by fractionating a culture filtrate of
      Aspergillus kawachii grown on L-rhamnose as the sole carbon source. The alpha-L
      rhamnosidase had a molecular mass of 90 kDa and a high degree of N-glycosylation
      of approximately 22%. The enzyme exhibited optimal activity at pH 4.0 and
      temperature of 50 degrees C. Further, it was observed to be thermostable, and it
      retained more than 80% of its original activity following incubation at 60
      degrees C for 1 h. Its T (50) value was determined to be 72 degrees C. The enzyme
      was able to hydrolyze alpha-1,2- and alpha-1,6-glycosidic bonds. The specific
      activity of the enzyme was higher toward naringin than toward hesperidin. The A.
      kawachii alpha-L-rhamnosidase-encoding gene (Ak-rhaA) codes for a 655-amino-acid
      protein. Based on the amino acid sequence deduced from the cDNA, the protein
      possessed 13 potential N-glycosylation recognition sites and exhibited a high
      degree of sequence identity (up to 75%) with the alpha-L-rhamnosidases belonging
      to the glycoside hydrolase family 78 from Aspergillus aculeatus and with
      hypothetical Aspergillus oryzae and Aspergillus fumigatus proteins.

PMID- 18633610
TI  - Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth.
AB  - Intravenously-applied bacteria tend to accumulate in tumors and can sporadically
      lead to tumor regression. Systemic administration of attenuated Salmonella
      typhimurium is safe and has shown no significant adverse effects in humans. The
      purpose of this study was to test the hypothesis that engineering S. typhimurium
      to express a chemokine, CCL21, would increase anti-tumor activity. We engineered
      an attenuated strain of S. typhimurium to produce the chemokine CCL21. Attenuated
      S. typhimurium expressing CCL21 significantly inhibited the growth of primary
      tumors and pulmonary metastases in preclinical models of multi-drug-resistant
      murine carcinomas, while control bacteria did not. Histological analysis of
      tumors showed marked inflammatory cell infiltrates in mice treated with CCL21
      expressing but not control bacteria. Levels of cytokines and chemokines known to
      be induced by CCL21 [e.g., interferon-gamma (INFgamma), CXCL9, and CXCL10] were
      significantly elevated in tumors of mice treated with CCL21-expressing but not
      control S. typhimurium. The anti-tumor activity was found to be dependent on CD4-
      and CD8-expressing cells, based on antibody-mediated in vivo immuno-depletion
      experiments. Anti-tumor activity was achieved without evidence of toxicity. In
      summary, chemokine-expressing, attenuated bacteria may provide a novel approach
      to cancer immunotherapy for effective and well-tolerated in vivo delivery of
      immunomodulatory proteins.

PMID- 18633611
TI  - Bristow-Latarjet procedure with specific instrumentation: study of 34 cases.
AB  - A Bristow-Latarjet procedure with specific instrumentation was performed for
      recurrent dislocation or subluxation of the glenohumeral joint in 34 patients.
      The procedure was performed through a subscapularis splitting approach with three
      specific instruments and a special screw. The clinical outcome was assessed by
      the Duplay and the Constant scores. Radiographic study was conducted on 23
      patients and CT scan in 11 patients. Of the 27 patients interviewed 92% were
      satisfied. Of the 23 patients examined, 15 had an excellent Duplay score, four a
      good score, three a medium score, and only one had a bad score. One patient had
      subluxation episodes, and one patient was revised after a redislocation following
      violent trauma. On the standard radiographs, all bone blocks were in the correct
      position. A pseudarthrosis was diagnosed in the patient with subluxation
      episodes. This device simplifies the surgical technique and provides
      reproducibility to the procedure.

PMID- 18633612
TI  - Risk factors for osteonecrosis of the femoral head in patients with sickle cell
      disease.
AB  - The mechanisms involved in the pathogenesis of osteonecrosis of the femoral head
      in sickle cell disease are not fully known. The aim of this study was to identify
      risk factors for osteonecrosis of the femoral head among sickle cell disease
      patients. Clinical (frequency of painful crises and hospitalisation) and
      laboratory parameters (euglobulin clot lysis time, haematocrit, platelet count,
      and leucocyte count) of 25 consecutive patients with avascular necrosis of the
      femoral head from sickle cell disease were compared with those of 26 age- and sex
      matched sickle cell disease patients without avascular necrosis. The group with
      avascular necrosis of the femoral head (mean age 23.7+/-4.9 years) had a
      significantly higher rate of painful crises (p = 0.03) and hospitalisations per
      year (p = 0.002) than the group without avascular necrosis (mean age 21.6+/-5.2
      years). The group with avascular necrosis also had a significantly higher
      euglobulin clot lysis time than the group without avascular necrosis (p = 0.001).
      In conclusion, it appears that not all patients with sickle cell disease have
      impaired fibrinolytic activity. The aetiology of avascular necrosis in sickle
      cell disease is multifactorial.

PMID- 18633613
TI  - Reversible cardiac dysfunction without myocytolysis related to all-trans retinoic
      acid administration during induction therapy of acute promyelocytic leukemia.

PMID- 18633614
TI  - Chronic myeloid leukemia presenting late in pregnancy. Report of a case and a
      questionnaire reflecting diversity in management options.

PMID- 18633615
TI  - The application of conventional cytogenetics, FISH, and RT-PCR to detect genetic
      changes in 70 children with ALL.
AB  - We investigated bone marrow cells of 70 acute lymphoblastic leukemia children by
      conventional cytogenetics (CC), fluorescence in situ hybridization (FISH), and
      reverse transcription polymerase chain reaction (RT-PCR) methods. CC and RT-PCR
      for fusion genes BCR/ABL, MLL/AF4, E2A/PBX1, TEL/AML1 were performed at diagnosis
      in each patient. FISH was performed to verify the presence of fusion genes and
      MLL rearrangements and to estimate the percentage of abnormal cells. Karyotypes
      were obtained in 59 (84%) of 70 cases. Thirty-five (59%) of 59 cases revealed
      chromosome aberrations. Hyperdiploidy>50 chromosomes was present in nine cases,
      hyperdiploidy 47-50 chromosomes in six, pseudodiploidy in 15, and hypodiploidy in
      five. BCR/ABL was present in two cases, PBX1/E2A in two, and TEL/AML1 in 14.
      MLL/AF4 was not found, but the rearrangements of MLL gene were present in five
      children. The addition of RT-PCR and FISH to CC was of the utmost importance. One
      of two Ph translocations and one of two t(1;19) were first revealed by RT-PCR.
      Moreover, FISH showed the percentage of TEL/AML1(+) cells that turned to be an
      important prognostic factor. The outcome was the best for the children with
      hyperdiploidy>50 chromosomes without structural changes. It was also good for
      those with TEL/AML1 present in >or=80% of cells without chromosome aberrations.
      The presence of pseudodiploidy correlated with poor outcome. The outcome for
      patients with t(9;22)-BCR/ABL or 11q23-MLL rearrangement was the worst in study
      group. The presence of BCR/ABL caused eight times increase of risk of death; MLL
      rearrangements caused 12 times increase.

PMID- 18633616
TI  - The expression and prognostic significance of platelet-derived growth factor
      receptor alpha in mature T- and natural killer-cell lymphomas.
AB  - Platelet-derived growth factor receptor alpha (PDGFRA) is important in numerous
      malignancies and can serve as a target for therapeutic strategy. We aimed to
      assess the role of PDGFRA expression in mature T- and natural killer (NK)-cell
      lymphomas. We used immunohistochemistry to analyze PDGFRA expression in mature T-
      and NK-cell lymphomas in tissue samples from 50 patients. In positive samples, we
      then did a mutational analysis of the PDGFRA gene on exons 10, 12, 14, and 18.
      The relationship between PDGFRA expression and overall survival in mature T- and
      NK-cell lymphomas was statistically analyzed in the study. We analyzed PDGFRA
      expression in four subtypes: angioimmunoblastic T-cell lymphoma (3/8, 37.5%);
      anaplastic large cell lymphoma (5/7, 71.4%); NK/T-cell lymphoma, nasal type
      (9/12, 75%); and peripheral T-cell lymphoma, unspecified (PTCLu; 7/23, 30.4%). It
      was lower in PTCLu than in other subtypes (30.4% vs. 63%, p=0.022). PDGFRA
      expression was not related to PDGFRA gene mutation. Overall survival in mature T-
      and NK-cell lymphomas correlated significantly with disease subtypes and an
      international prognostic index but not PDGFRA expression. Our study showed that
      PDGFRA expression was different in mature T- and NK-cell lymphomas. PDGFRA
      expression in PTCLu was lower in the present study than in previous reports done
      in Western countries. It suggests that this disease is biologically distinct in
      different races (30.4% vs. 91-100%).

PMID- 18633617
TI  - Idiopathic esophageal ulcers after autologous hemopoetic stem cell transplant:
      possible role of IgA levels.

PMID- 18633618
TI  - Analysis of C282Y and H63D mutations of the hemochromatosis gene (HFE) in blood
      donors from Cordoba, Argentina.

PMID- 18633619
TI  - BCNU-sequestration by metallothioneins may contribute to resistance in a
      medulloblastoma cell line.
AB  - PURPOSE: Resistance of neoplastic cells to the alkylating drug BCNU [1,3-bis(2
      chloroethyl)-1-nitrosourea] has been correlated with expression of O (6)
      methylguanine-DNA methyltransferase, which repairs the O (6)-chloroethylguanine
      produced by the drug. Other possible mechanisms of resistance include raised
      levels of glutathione or increased repair of the DNA interstrand cross-links
      formed by BCNU. Transcriptional profiling revealed the upregulation of several
      metallothionein (MT) genes in a BCNU-resistant medulloblastoma cell line [D341
      MED (OBR)] relative to its parental line. Previous studies have shown that MTs,
      through their reactive thiol groups can quench nitrogen mustard-derived
      alkylating drugs. In this report, we evaluate whether MTs can also quench BCNU.
      METHODS: To demonstrate the binding of BCNU to MT, we used an assay that measured
      the release of the MT-bound divalent cations (Zn(2+), Cd(2+)) upon their
      displacement by the drug. We also measured the decomposition rates of BCNU at
      those reaction conditions. RESULTS: The rate of release of the cations was higher
      in pH 7.4 than at pH 7.0, which is likely a result of more rapid decomposition of
      BCNU (thus faster release of MT-binding intermediate) at pH 7.4 than at pH 7.0.
      CONCLUSION: We demonstrate that resistance to BCNU may be a result of elevated
      levels of MTs which act by sequestering the drug's decomposition product(s).

PMID- 18633620
TI  - [Molecular pathology of testicular germ cell tumors: an update].
AB  - Germ cell tumors (GCT) comprise a heterogeneous group of benign and malignant
      tumors. Based on their different biological characteristics and their origin,
      five types of GCT are classified. Among these, malignant seminomatous and non
      seminomatous GCT in males and females are designated as type II GCT. They occur
      most frequently as malignant testicular GCTs. Many characteristics of type II GCT
      can be linked to embryonic stem cells. Intratubular germ cell neoplasia,
      unclassified (IGCNU) is the precursor of type II GCT and derives from
      undifferentiated germ cells, gonocytes, which persist in the newborn testis and
      escape the normal differentiation process. It is suggested that Exon-17-activated
      mutations of the receptor tyrosine kinase, c-KIT, occur early in germ cell
      development and that gonocytes with an activated c-KIT receptor are restricted in
      their differentiation, thereby escaping normal development. New diagnostic
      markers for neoplastic germ cells, including OCT3/4 and AP-2gamma, are
      specifically detected in IGCNU, seminomas and embryonal carcinomas and are
      helpful in the differentiation of type II GCT from other malignant tumors.

PMID- 18633621
TI  - A case report: pregnancy-induced severe osteoporosis with eight vertebral
      fractures.
AB  - Osteoporosis associated with pregnancy and lactation is a rare condition. The
      prevalence, etiology and its pathogenesis is unknown. It causes one or more
      vertebral fractures with severe, prolonged back pain and height loss in affected
      women. Majority of the cases are seen in the third trimester or just after
      delivery in primagravid women. In this case report, a 30-year-old woman who had
      severe pregnancy-induced osteoporosis with 8 vertebral fractures was presented.
      During last month of her first pregnancy she had moderate back pain. After
      delivery, the back pain has gotten worse. The radiological examinations have
      shown that there was 50% in T6, T8 and T10; 30% in L2; 20% in L1 height loss and
      biconcave vertebral images in L3-5. In the bone mineral density, L2-4 T score was
      -4.7 and total femoral T score was -3.1. There was no abnormality in the
      laboratory findings except mild elevation in alkaline phosphates. Although
      pregnancy-associated osteoporosis is a rare condition, when pain occurs in the
      last trimester or early postpartum period, it should be considered in
      differential diagnosis.

PMID- 18633622
TI  - Lateral line units in the amphibian brain could integrate wave curvatures.
AB  - Aquatic predators like Xenopus laevis exploit mechano-sensory lateral lines to
      localise prey on the water surface by its wave emissions. In terms of distance,
      hypothetically, the source of a concentric wave could be centrally represented
      based on wave curvatures: for Xenopus, we present a first sample of 98
      extracellularly recorded brainstem and midbrain responses to waves with
      curvatures ranging from 22.2-11.1 m(-1). At the frog, concurrently, wave
      amplitudes and their spectral composition were kept stable. Notably, 61% of 98
      units displayed curvature-dependent spike rates, suggesting that wave curvatures
      could support an extraction of source distances in the amphibian brain.

PMID- 18633623
TI  - Down syndrome and the enteric nervous system.
AB  - Down syndrome (DS) is the most common chromosomal abnormality occurring in
      humans. Up to 77% of DS children have associated gastrointestinal (GI)
      abnormalities, which may be structural or functional in nature. Functional
      disturbances may, in turn, affect the outcome of corrective surgical procedures,
      prompting to caution. It is becoming clear that the processes affecting the
      enteric nervous system (ENS) in DS not only affect the micro-anatomy but also
      nerve function, and there is some histological evidence of ENS variations in both
      human and DS animal models. This suggests that developmental disorders of the ENS
      are probably fundamental to the functional GI disturbances encountered in
      patients with DS. The anomalous brain development, function and resulting
      intellectual impairment associated with DS appears to result from the genetic
      imbalance created by the trisomy of chromosome 21. The possible links between the
      brain, GI and ENS involvement are not as yet entirely clear. Neurotropic factors
      affecting brain development during embryogenesis are probably interlinked with
      ENS development, but the precise mechanism of how this occurs has yet to be
      established. This study explores what is known about the ENS dysfunction in DS
      and reviews the possible importance of chromosome 21 located and other genes in
      its etiology. Functional motor disturbances of the esophagus and colon are not
      uncommon and may be congenital or acquired in nature. The most prominent of these
      include esophageal dysmotility syndromes (e.g. achalasia, gastroesophageal
      reflux, dysphagia) as well as a higher incidence of chronic constipation and
      Hirschsprung's disease (HSCR) (2-15%) occurring in association with DS.
      Chromosome 21 itself is thought to be the site of a modifier gene for HSCR.
      Recently identified candidate genetic mechanisms provide unique insights into the
      genetic background of the neurological and cognitive disorders associated with
      DS. Although the role of the triplicated chromosome 21 and genetic dosage remain
      important, the additional role of other chromosome 21 genes in the etiology of
      ENS developmental anomalies remains undetermined and requires ongoing research.

PMID- 18633624
TI  - Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of
      rectal carcinoma and the surrogate endpoint CRM status.
AB  - AIM: Is it possible to reduce the frequency of neoadjuvant therapy for rectal
      carcinoma and nevertheless achieve a rate of more than 90% circumferential
      resection margin (CRM)-negative resection specimens by a novel concept of
      magnetic resonance imaging (MRI)-based therapy planning? MATERIALS AND METHODS:
      One hundred eighty-one patients from Berlin and Mainz, Germany, with primary
      rectal carcinoma, without distant metastasis, underwent radical surgery with
      curative intention. Surgical procedures applied were anterior resection with
      total mesorectal excision (TME) or partial mesorectal excision (PME; PME for
      tumours of the upper rectum) or abdominoperineal excision with TME. RESULTS: With
      MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62
      of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170
      of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was
      CRM-positive. Patients selected for primary surgery had CRM-negative specimens on
      histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a
      lower rate of clear margin: 56 of 62 (90%). CONCLUSION: By applying a MRI-based
      indication, the frequency of neoadjuvant treatment with its acute and late
      adverse effects can be reduced to 30-35% without reduction of pathologically CRM
      negative resection specimens and, thus, without the danger of worsening the
      oncological long-term results. This concept should be confirmed in prospective
      multicentre observation studies with quality assurance of MRI, surgery and
      pathology.

PMID- 18633625
TI  - Surgical treatment for anorectal malignant melanoma: report of five cases and
      review of 79 Japanese cases.
AB  - INTRODUCTION: Anorectal malignant melanoma (AMM) is a relatively rare disease.
      Because of its poor prognosis, the optimal surgical treatment for AMM is still
      controversial and difficult to determine. In this paper, we report five cases of
      AMM that have been treated by surgery and/or other methods at Shinshu University
      Hospital within the last decade. We also review the present five cases along with
      74 other Japanese cases reported between 1997 and 2006 and discuss the role of
      surgery in the treatment of AMM. RESULTS AND DISCUSSION: Among our AMM patients,
      two who underwent radical abdominoperineal resection had long survival, while the
      other three patients who underwent palliative surgery had a poor outcome. On the
      total of 79 AMM patients, those who underwent curative surgery had a better
      outcome than those who underwent palliative surgery (p < 0.0001). Furthermore,
      the outcome of AMM patients at stages 0 and I was better than that of AMM
      patients at stages II, III, and IV (p < 0.0001). There was no significant
      difference in survival between AMM patients with and without adjuvant
      chemotherapy. CONCLUSION: In conclusion, AMM patients treated by curative surgery
      can expect long-term survival, although the usefulness of adjuvant chemotherapy
      for AMM patients is controversial.

PMID- 18633626
TI  - Inflammation modulates fibronectin isoform expression in colonic lamina propria
      fibroblasts (CLPF).
AB  - BACKGROUND: Migration of colonic lamina propria fibroblasts (CLPF) plays an
      important role during mucosal wound healing as well as fibrosis and fistula
      formation in Crohn's disease (CD). Recently, we showed that the migratory
      potential of CD-CLPF was significantly reduced compared to control CLPF. Fistula
      derived CD-CLPF migrated less and fibrosis-CLPF more than CLPF from inflamed CD
      mucosa. These changes in migratory behavior were associated with changes in
      production of the migration-inducing fibronectin (FN) isoforms ED-A and ED-B. A
      permanent reduction of the migratory potential of CLPF was mediated by IFN-gamma
      and tumor necrosis factor (TNF) modulate FN isofom expression in CLPF and thereby
      might regulate CLPF migration. MATERIALS AND METHODS: Control CLPF were incubated
      for 72 h with IFN-gamma, TNF, IFN-gamma plus TNF, or TGF-beta1. Messenger RNA
      (mRNA) was isolated and expression of FN and isoforms ED-A and ED-B was
      quantified by real-time polymerase chain reaction. FN, ED-A, and ED-B were
      investigated by Western blotting. FN receptor integrin alpha5beta1 was analyzed
      by FACS. RESULTS: No difference was found for the surface display of integrin
      alpha5beta1 between stimulated and non-stimulated cells. In TGF-beta1 incubated
      CLPF mRNA amount of FN and isoforms ED-A and ED-B was slightly increased. IFN
      gamma only decreased FN in CLPF, TNF significantly reduced FN-mRNA by 40%, FN ED
      A mRNA by 25%, and ED-B mRNA by 50%. The TNF-mediated mRNA downregulation
      resulted in a decreased protein amount as revealed by Western blotting.
      CONCLUSION: Cytokines such as IFN-gamma, TNF, and TGF-beta1 modulate the
      production of fibronectin isoforms. Our data indicate that inflammation-induced
      modulation of FN-isoform production is involved in the alterations of migratory
      potential of CLPF isolated from CD mucosa.

PMID- 18633627
TI  - [The current structure of rheumatology in German universities. The Rhesus and
      RISA-II studies].
AB  - The teaching of rheumatology requires competent rheumatological structures in
      German university hospitals. In 2002, the nationwide 'RISA' survey on the extent
      and quality of rheumatological training in Germany brought a variety of deficits
      to light. In the same year, a new law regulating the licensing process to
      practise medicine came into force. Since this law aimed at a more practise-based
      training of medical students, hopes were high that the conditions for the
      rheumatological education of students would improve over time. Therefore, our
      survey was repeated four years later, supplemented by a questionnaire covering
      scientific activities in rheumatology at university hospitals. In addition,
      another survey, known as the Rhesus study, was started in 2007 to analyse the
      size and capacity of rheumatological departments and units at German medical
      faculties. The results show that rheumatology represents one of the smallest
      subjects of internal medicine in Germany. Several German university hospitals do
      not include a rheumatological department at all. Since 2002, no significant
      progress has been made with regard to the extent of training for medical students
      in rheumatology, and the new licensing law has not yet shown beneficial effects
      in this respect. The current data represent only a snap-shot. The development of
      rheumatology requires cautious observation to prevent this important area of
      medicine from being sacrificed to economic interests or structural changes.

PMID- 18633628
TI  - [The position of rheumatology from the perspective of general practitioners. A
      survey on the quality and extent of medical training, specialty training and
      postgraduate training of general practitioners for internal medicine].
AB  - A high level of competence among general practitioners (GPs) is essential in the
      primary care of patients with rheumatic diseases. A survey among 172 GPs revealed
      that GP care for a large number of rheumatologic patients, mostly with non
      inflammatory rheumatic disorders. However, compared to the majority of other
      subspecialties of internal medicine, rheumatology is less well represented in
      student education, specialty training and postgraduate education.

PMID- 18633629
TI  - [Documentation of outpatient treatment of Paget's disease in Westphalia-Lippe.
      Descriptive analysis of statutory health insurance data for the year 2005].
AB  - GOAL: Inpatient health care data are often used as a source of information for
      health reporting in Germany, despite the fact that a lot of diseases are
      predominantly treated in the outpatient sector. This study provides a first
      overview of the outpatient care situation in relation to Paget's disease. METHOD:
      Outpatient care data from the Association of Statutory Health Insurance
      Physicians constituted the database for a descriptive analysis, capturing the
      state of medical care for the rare rheumatic illness Paget's disease
      (Osteodystrophia deformans) in the region of East Westphalia-Lippe in 2005.
      RESULTS: While the health report of North Rhine-Westphalia documents a total of
      56 cases of M. Paget discharged from hospital for the year 2003, 166 patients
      suffering from Paget's disease consulted an practice-based physician in 2005 in
      the district of Detmold alone. The latter figure corresponds to 8.0 treated
      patients per 100.000 inhabitants. The treatment rates of men and women are
      comparable. The probability of treatment increases with advancing age. On
      average, patients with Paget's disease are 65.6 years old (SD=15.4 years). Almost
      90% of the diagnoses of Paget's disease are classified as M88.9 according to ICD
      10; more exact localisations are provided only for relatively few cases. Nearly a
      quarter of the cases (24.1%) are treated by general practitioners and internists.
      Anaesthetists treated 17.5% of the patients and orthopaedists 16.9%. In addition,
      ophthalmologists treat a considerable proportion of cases (12.0%). CONCLUSION:
      Consistent with the rareness of Paget's disease, the treatment data are as low as
      expected. However, the results show that routinely collected health care data
      allow insights into morbidity structures within the outpatient sector. It follows
      that for statutory health insurants (approximately 90% of the population) there
      should be an extension of health reporting to diseases that are mainly treated in
      outpatient settings.

PMID- 18633630
TI  - [Fractalkine--a proinflammatory chemokine in rheumatoid arthritis].
AB  - Fractalkine (CX3CL1), so far the only member of the CX3C class of chemokines, and
      its receptor, CX3CR1, are strongly expressed in the chronically inflamed synovial
      tissue of patients with rheumatoid arthritis (RA). Due to the specific binding of
      Fractalkine to its receptor, many proinflammatory reactions involved in the
      pathogenesis of RA are triggered. Functionally, fractalkine plays an important
      proinflammatory role in RA pathogenesis as characterized by induction of synovial
      angiogenesis, chemotaxis, activation of monocytes and T cells as well as the
      stimulation of proliferation and synthesis of matrix degrading enzymes (matrix
      metalloproteinases, MMP) in synovial fibroblasts. Fractalkine thus may represent
      a novel target molecule for therapeutic intervention in RA.

PMID- 18633631
TI  - Similar results with 21 Kudo and 21 Souter-Strathclyde total elbow arthroplasties
      in patients with rheumatoid arthritis.
AB  - INTRODUCTION: The results of different prostheses used for total elbow
      arthroplasty (TEA) in rheumatoid arthritis (RA) have been reported in only a few
      studies. Small differences in survival or function between implants have been
      reported. We retrospectively evaluated the results of 42 Souter-Strathclyde and
      Kudo TEAs. MATERIALS AND METHODS: Between 1988 and 1994, 21 consecutive patients
      with RA and severe elbow destruction underwent a Souter-Strathclyde TEA. Between
      1994 and 1998, another group comprising 21 consecutive patients with RA with
      severe elbow destruction underwent a Kudo TEA. RESULTS: There were six revisions
      for the groups combined, including four aseptic loosenings, one fracture and one
      liner wear and metallosis. The 5-year survival for the Souter-Strathclyde and the
      Kudo were 85% (95% CI 69-100) and 95% (95% CI 85-100), respectively. The
      difference between the groups was not statistically significant as tested by the
      Cox regression analysis. The majority of the patients were free of pain at follow
      up. More than half of the patients were able to perform only light housekeeping
      tasks and a considerable proportion even had difficulties in maintaining personal
      hygiene. The elbow range of motion improved only slightly after the operation.
      CONCLUSION: Both the Souter-Strathclyde and the Kudo TEAs provide good pain
      relief in the arthritic elbow leading to high patient satisfaction despite the
      residual disabilities. Only small differences in the results between the Souter
      Strathclyde and the Kudo TEAs were found. More than half of the patients were
      able to perform only light housekeeping tasks and a considerable proportion even
      had difficulties in maintaining personal hygiene. The elbow range of motion
      improved only slightly after the operation.

PMID- 18633632
TI  - Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated
      acute phase atopic dermatitis by inducing regulatory T cells.
AB  - Increase in the number of patients with atopic dermatitis (AD) has been recently
      reported. T helper (Th) cells that infiltrate AD skin lesions are Th2-type
      dominant; reduced exposure to environmental Th1-cytokine-inducing microbes is
      believed to contribute to the increased number of AD patients. Regulatory type
      immune responses have been also associated with the occurrence of AD. It has been
      reported that antigen 85B (Ag85B) purified from mycobacteria is a potent inducer
      of Th1-type immune response in mice as well as in humans. In this study, we have
      examined the effect of plasmid DNA encoding Ag85B derived from Mycobacterium
      kansasii on AD skin lesions induced by oxazolone (OX) application. Th2-cytokine
      mediated mouse AD model with immediate type response followed by a late phase
      reaction was developed by repeated applications of low-dose OX to sensitized
      mice. Mice were immunized with plasmid DNA encoding cDNA of Ag85B before OX
      sensitization or during repeated elicitation phase. Both therapies were
      associated with significant suppression of immediate type response, clinical
      appearance, dermal cell infiltration, reduced IL-4 production, and augmented IFN
      gamma mRNA expression compared to placebo-treated mice. Additionally, increased
      number of Foxp3(+) regulatory T cells were observed in the skin sections in Ag85B
      treated mice. The results of this study suggest that Ag85B DNA vaccine is a
      potential therapy for Th2 type dermatitis.

PMID- 18633633
TI  - Hepatic gap junctions in the hepatocarcinogen-resistant DRH rat.
AB  - Although the gap junction or connexin (Cx) is considered to be a tumor
      suppressor, it is also required for tumor promotion. Therefore, we examined
      hepatic gap junctions in hepatocarcinogen-resistant (DRH) rats. Specifically, we
      investigated gap junction structure and Cx32 expression during normal conditions
      and in response to a hepatocarcinogen, 3'-methyl-4-dimethylaminoazobenzene (3'
      MeDAB). On a basal diet without 3'-MeDAB, hepatic gap junctions and Cx32 protein
      expression were greater in DRH rats than in control Donryu rats, as evidenced by
      morphometry, immunohistochemistry and immunoblotting. On a diet containing 3'
      MeDAB, gap junctions and expressed Cx32 were increased significantly in Donryu
      rats, but not in DRH rats. In this condition, Donryu rats lost weight but DRH
      rats increased relative liver weight. After 3'-MeDAB treatment, cathepsin D
      expression in hepatocytes was significantly increased only in Donryu rats,
      indicating that DRH rats were less susceptible to 3'-MeDAB. The abundance of
      mitogen-activated protein kinase, some constituent of which might be associated
      with the degree of Cx protein phosphorylation, was reduced to a greater extent in
      Donryu than in DRH rats after 3'-MeDAB treatment. The resistance of DRH rats to
      carcinogenesis may be due partially to their stabilized gap junctions, which
      could coordinate metabolic coupling to evade 3'-MeDAB toxicity.

PMID- 18633635
TI  - Measurements of clothing insulation with a thermal manikin operating under the
      thermal comfort regulation mode: comparative analysis of the calculation methods.
AB  - The present work is dedicated to a comparative analysis of calculation methods
      about clothing insulation with a thermal manikin operating under the thermal
      comfort regulation mode. The serial, global, and parallel calculation methods are
      considered and the thermal insulation results for garments (30) and ensembles (9)
      are discussed. The serial and parallel methods presents the higher and lower
      values, respectively, and the differences were sometimes significant. Considering
      the results for the effective thermal insulation, the mean values of the relative
      differences between the serial and global methods were 25.7% for the daily wear
      garments, 45.2% for the cold protective garments and 38.5% for the ensembles. The
      corresponding mean values for the global and parallel methods were 8.7, 15.8, and
      10.5%, respectively. Since any uneven clothing insulation is to be expected as a
      source of error, particular care must be required when the calculation methods
      deal with cold protective clothing.

PMID- 18633634
TI  - TLR9 is expressed in idiopathic interstitial pneumonia and its activation
      promotes in vitro myofibroblast differentiation.
AB  - Infectious diseases can be cofactors in idiopathic interstitial pneumonias (IIP)
      pathogenesis; recent data suggests that toll-like receptors 9 (TLR9) ligands
      contribute to experimental chronic tissue remodeling. Real-time TAQMAN and
      immunohistochemical analysis of IIP normal surgical lung biopsies (SLBs), primary
      fibroblast lines grown from both IIP and normal SLBs indicate that TLR9 is
      prominently and differentially expressed in a disease-specific manner. TLR9
      expression was increased in biopsies from patients with IIP compared with normal
      lung biopsies and its expression is localized to areas of marked interstitial
      fibrosis. TLR9 in fibroblasts appeared to be increased by profibrotic Th2
      cytokines (IL-4 and IL-13) and this was true in fibroblasts cultured from the
      most severe form of IIP, idiopathic pulmonary fibrosis (IPF) SLBs, in non
      specific interstitial pneumonia fibroblast lines, and in normal fibroblasts.
      Finally, confocal microscopy studies have shown that TLR9 activation by its
      synthetic agonist CpG-ODN significantly increased the expression of alpha smooth
      muscle actin, the main marker of myofibroblast differentiation. These data
      indicate that TLR9 expression may drive the abnormal tissue healing response in
      severe forms of IIP and its activation can have a key role in myofibroblast
      differentiation promoting the progression of disease during the terminal phase of
      IPF.

PMID- 18633636
TI  - Probiotics in patients with severe acute pancreatitis: a meta-analysis.
AB  - BACKGROUND: This study focuses on probiotics in patients with severe acute
      pancreatitis. It assesses whether enteral feeding with probiotics use reduces
      infected necrosis and death in severe acute pancreatitis. MATERIALS AND METHODS:
      We searched the Cochrane Library, Medline, Embase, and Chinese Biomedicine
      Database. Quality assessment and data extraction were done by two reviewers
      independently. The statistical analysis was performed by RevMan4.2.10 software.
      The result was expressed with odds ratio (OR) for the categorical variable.
      RESULTS: Four studies were included. The result showed that using probiotics
      could not reduce the risk of infection pancreatic necrosis (OR = 0.56, 95% CI
      [0.13, 2.35]). There is no significant difference between the two groups in
      mortality (OR = 0.83, 95% CI [0.14, 4.83]), the mean duration of hospital (WMD = 
      1.20, 95% CI [-13.13, 10.92]) and the required operation (OR = 0.59, 95% CI
      [0.11, 3.07]). CONCLUSION: The present study showed the enteral feeding with
      probiotic could not reduce the infected necrosis and mortality. Future large
      scale, high-quality, placebo-controlled, double-blind trials are needed.

PMID- 18633637
TI  - Late outcome after surgical management of carotid body tumors from a 20-year
      single-center experience.
AB  - BACKGROUND AND AIMS: Surgical resection is the treatment of choice for carotid
      body tumors. The aim of this study was to assess not only the perioperative, but
      also the long-term outcome after surgical treatment. PATIENTS/METHODS: All
      patients that were operated on a carotid body tumor at our institution between
      1986 and 2006 were reviewed. Data collection included patient profile,
      intraoperative findings and postoperative outcome. RESULTS: Seventeen patients
      (11 female, six male) with 17 carotid body tumors (12 right, five left sided)
      were identified. Mean patient age at treatment was 49 years (range 19 to 76
      years). Eight patients (47.1%) had large Shamblin type III tumors. Complete tumor
      resection was achieved in 16 of 17 cases (94.1%). Malignacy could not be proven
      in any patient. The 30-day mortality and stroke rates were 0. The incidence of
      temporary and permanent cranial nerve deficit was 41.2% and 11.8%, respectively.
      Patients with type III tumors had significantly higher risk of neurologic
      complications than patients with smaller tumors (p = 0.0152). The median
      postoperative follow-up was 6.4 years (range 1.5 to 20 years). The overall
      survival rate was 82.4%; the disease-specific survival rate was 94.1% (16 of 17
      patients). One patient (5.6%) died of local tumor recurrence 3 years after a R1
      resection. All the other patients showed no signs of local recurrence or
      metastases. CONCLUSIONS: The surgical therapy of carotid body tumors shows low
      long-term morbidity, mortality, and recurrence rates. Cranial nerve injury is
      mostly temporary but a relevant procedure-related complication. Surgical
      resection is indicated also for small, asympomatic tumors, because of the
      uncomplicated resectability of these tumors.

PMID- 18633638
TI  - The benefits of standardizing the operative procedure for the assistant in
      laparoscopy-assisted gastrectomy for gastric cancer.
AB  - BACKGROUND AND AIM: Laparoscopy-assisted distal gastrectomy (LADG) has not yet
      been widely adopted for the treatment of gastric cancers because of the perceived
      complexity of the procedure. In addition to the proficiency of the operator,
      other factors could potentially be optimized to improve postoperative outcomes.
      The aim of this study was to evaluate a standardized operative procedure for
      assistants performing LADG. MATERIALS AND METHODS: Of 114 patients, 64 initially
      underwent conventional LADG (CLDG) and then 50 underwent standardized procedure
      (SLDG) in which the role of assistant in LADG was completely established.
      Parameters compared for the SLDG and CLDG groups were operation time, estimated
      blood loss, intra- or postoperative complications, preservation of the vagus
      nerve, and the number of pathologically examined lymph nodes. RESULTS: The
      operation time for the SLDG procedure (mean +/- SE, 229 +/- 6 min) was shorter
      than for the CLDG procedure (261 +/- 8 min; P < 0.002), and the estimated blood
      loss for SLDG (57 +/- 7 ml) was less than for CLDG (108 +/- 17 ml, P < 0.004).
      The celiac branch of the vagus nerve was preserved in 73% of SLDG patients
      compared with 52% of CLDG patients (P < 0.03). More lymph nodes were
      pathologically examined in SLDG patients (38.3 +/- 1.5) than in CLDG patients
      (32.5 +/- 1.8, P = 0.02). CONCLUSIONS: Standardization of the LADG procedure for
      assistants enabled a shorter operation time, reduced blood loss, a higher rate of
      vagus nerve preservation, and more accurate lymph node dissection.

PMID- 18633639
TI  - Complications to thyroid surgery: results as reported in a database from a
      multicenter audit comprising 3,660 patients.
AB  - BACKGROUND AND AIM: During recent years, more radical surgery for thyroid
      disease, i.e., total instead of subtotal resection, has been evident. Results
      following this strategy on national levels are scarce. MATERIALS AND METHODS:
      From 2004 to 2006, 26 Scandinavian Departments registered 3,660 thyroid
      operations in a database. Risk factors for complications were analyzed with
      multiple logistic regression. RESULTS: After thyroidectomy, re-bleeding occurred
      in 2.1% and was associated with older age (OR 1.04; p < 0.0001) and male gender
      (OR 1.90; p = 0.014). Postoperative infection occurred in 1.6% and associated
      with lymph node operation (OR 8.18; p < 0.0001). Postoperative unilateral paresis
      of the recurrent laryngeal nerve was diagnosed 3.9% and bilateral paresis in
      0.2%. Unilateral paresis was associated with older age, intrathoracic goiter,
      thyreotoxicosis, and if routine laryngoscopy was practiced (OR 1.92; p = 0.0002).
      After 6 months, the incidence of nerve paresis was 0.97%. After bilateral thyroid
      surgery (n = 1,648), hypocalcaemia treated with vitamin D analogue occurred in
      9.9% of the patients at the first follow-up and in 4.4% after 6 months.
      CONCLUSION: Complications to thyroid surgery are not uncommon. The high frequency
      of hypocalcaemia treated with vitamin D after 6 months is a cause of concern.

PMID- 18633640
TI  - Adaptative modifications of right coronary myocytes voltage-gated K+ currents in
      rat with hypoxic pulmonary hypertension.
AB  - Chronic hypoxia (CH)-induced pulmonary hypertension (PHT) is well known to alter
      K+ channels in pulmonary myocytes. PHT induces right ventricle hypertrophy that
      increases oxygen demand; however, coronary blood flow and K+ channel adaptations
      of coronary myocytes during PHT remain unknown. We determined whether CH and PHT
      altered K+ currents and coronary reactivity and what impact they might have on
      right myocardial perfusion. Right ventricle perfusion, as attested by
      microspheres, was redistributed toward hypertrophied right ventricle [RV/LV
      (%)=0.59+/-0.07% in CH rats vs. 0.29+/-0.03 in control rats, P<0.05]. Whole-cell
      patch clamping showed a reduction of global outward current in hypoxic right
      coronary artery myocytes (H-RCA), whereas hypoxic left coronary artery myocytes
      exhibited an increase. K+ channel blockers revealed that a 4-aminopyridine (4AP)
      sensitive current (Kv current) was decreased in H-RCA (14.3+/-1.1 vs. 23.4+/-2.5
      pA/pF at 60 mV in control RCA, P<0.05) and increased in hypoxic left coronary
      artery myocytes (H-LCA; 26.4+/-3.8 vs. 11.8+/-1.6 pA/pF at 60 mV in control LCA,
      P<0.05). Constriction to 4AP was decreased in H-RCA when compared to normoxic
      control and increased in H-LCA when compared to LCA. Finally, we observed that
      the expression of Kv1.2 and Kv1.5 were lower in H-RCA than that in H-LCA. This
      study reveals that CH differentially regulates Kv channels in coronary myocytes.
      Hypoxia decreases Kv currents and therefore reduces vasoreactivity that
      contributes to an adaptative response leading to right hypertrophied ventricle
      perfusion enhancement at rest.

PMID- 18633641
TI  - Tissue expansion for correction of baldness in aplasia cutis congenita.
AB  - Aplasia cutis is a congenital absence of the skin, usually presenting on the
      scalp. In 20% of all cases, part of the skull is also absent. A residual area of
      baldness may still be present some years after surgical or conservative
      treatment. It is possible to excise the scarred hairless region and cover that
      area with expanded hair-bearing skin from the rest of the skull. We present three
      patients who underwent tissue expansion and discuss the indications and pitfalls
      of this procedure. CONCLUSION: Tissue expansion can be used to cover a residual
      alopecia defect in young children with aplasia cutis congenita and associated
      bone abnormalities. The quality of the bone appears to be normal in our three
      patients. We demonstrate that even in young children with aplasia cutis and an
      underlying bony defect, tissue expansion is a safe and effective modality as a
      second stage reconstruction procedure.

PMID- 18633642
TI  - Development of hippocampal sclerosis after a complex febrile seizure.
AB  - The role of prolonged febrile seizures in the genesis of hippocampal sclerosis is
      controversial; statistical analysis and data from epilepsy surgery suggest a
      causal relationship. A three-year-old boy had an initial febrile seizure with a
      transient postictal flaccid hemiparesis. Magnetic resonance imaging (MRI) showed
      no abnormality of the hippocampal areas of both sides. At the age of four a
      prolonged febrile seizure occurred. An MRI was done immediately and gave abnormal
      results in the right hippocampal area where T2-weighted and dark fluid sequences
      showed increased signal intensity; in diffusion-weighted sequences this region
      appeared hyperintense, which is in agreement with acute neuronal damage. Six
      weeks later the right hippocampal region still gave hyperintense signals in MRI
      (T2-weighted), while the diffusion coefficient was unremarkable. A final MRI scan
      was done 16 months following the second febrile seizure where the right
      hippocampal region still gave hyperintense signals and was reduced in size as is
      typical for hippocampal sclerosis. This case illustrates the development of a
      hippocampal lesion following a prolonged focal febrile seizure without any
      preexisting hippocampal lesion or positive family history. This suggests that
      prolonged febrile seizures alone can be a causative factor of hippocampal
      sclerosis.

PMID- 18633643
TI  - Immunoprotection of chickens against Eimeria acervulina by recombinant alpha
      tubulin protein.
AB  - Tubulins are heterodimeric molecules responsible for the polymerization of
      microtubules in apicomplexan parasites. The alpha-tubulin, a subcellular
      structural protein of Eimeria acervulina, was cloned and expressed in Escherichia
      coli as an alpha-tubulin-GST fusion protein. Immunogenicity of the recombinant
      protein was studied in chickens by subcutaneous injection of 50, 100, or 150
      microg of the protein with or without Freund's adjuvant. Immunization with 150
      microg alpha-tubulin-GST protein in combination with Freund's adjuvant conferred
      partial protection against E. acervulina oocyst challenge, as shown by a 36%
      reduction in oocyst shedding, a marked decrease in intestinal lesion score and a
      significant increase in body weight gain in comparison with the nonimmunized
      controls. The results suggest that alpha-tubulin protein may be used as an
      effective vaccine antigen for the control of Eimeria infection.

PMID- 18633644
TI  - Genetic polymorphism in Trypanosoma cruzi I isolated from Brazilian Northeast
      triatomines revealed by low-stringency single specific primer-polymerase chain
      reaction.
AB  - Different molecular markers have been employed for typing Trypanosoma cruzi
      strains from endemic areas of Chagas disease. The low-stringency single specific
      primer-polymerase chain reaction (LSSP-PCR) has been a sensitive and informative
      technique that uses the variable region of kinetoplast DNA minicircles as a
      genetic marker, allowing detection of DNA sequence variation. In the present
      study, we analyzed the intra-lineage genetic variability of the T. cruzi strains
      obtained from triatomine feces collected on filter paper FTA card by LSSP-PCR.
      The hybridization of the PCR products with a probe for the subgenus
      Schizotrypanum and a clone-specific probe from Dm28c confirmed the subgenus as T.
      (S.) cruzi and respective lineages as T. cruzi I. Phenetic analysis showed the
      presence of three clusters that diverged by different coefficients of similarity.
      Thirteen T. cruzi I genotypes were observed circulating among Triatoma
      pseudomaculata and Rhodnius nasutus from peridomiciliary and natural environments
      in five peri-urban and urban localities of Jaguaruana, Ceara, Brazil. These data
      indicate the importance of the circulation of T. cruzi I genotypes among T.
      pseudomaculata and R. nasutus in different environments and the possible risk of
      Chagas disease domestic transmission.

PMID- 18633645
TI  - Parasitism by bat flies (Diptera: Streblidae) on neotropical bats: effects of
      host body size, distribution, and abundance.
AB  - We examined the correlations between prevalence (proportion of infested
      individuals), mean intensity (number of parasites per infested individual), and
      the number of bat fly species parasitizing bats in Venezuela with host body mass,
      distribution, and abundance. Of 133 bat species sampled, 53 species in six
      families were captured frequently enough to allow estimation of their parasite
      loads. Over all species and six families, prevalence and mean intensity were
      uncorrelated with these variables, but the number of fly species was correlated
      with host body mass. Correlations of parasitism with body mass were strengthened
      among the 44 species of Phyllostomidae. Earlier studies showed that bat roosting
      habits influence their parasitism by bat flies with more permanent, enclosed
      roosts being with heavier parasitism. Multiple regressions of all measures of
      parasitism showed that roosting habits and host body mass, respectively, were the
      first variables to enter stepwise regressions, together accounting for 20-43% of
      the variation in measures of parasitism. Lack of correlation between proxies of
      distribution and abundance with parasitism is taken to indicate that proximate
      factors such as host-as-habitat, social groupings, and roost microhabitat take
      precedence over species-wide attributes like commonness and ubiquity.

PMID- 18633646
TI  - Acanthamoebicidal activity of Fusarium sp. Tlau3, an endophytic fungus from
      Thunbergia laurifolia Lindl.
AB  - A fungal endophyte identified as Fusarium sp. Tlau3 was isolated from fresh twig
      of Thunbergia laurifolia Lindl., a Thai medicinal plant collected from the forest
      of Chiang Mai Province, Northern Thailand. The fungus was grown on a medium
      containing yeast extracts and sucrose. The fungal metabolites were isolated from
      the culture broth by dichloromethane extraction, isooctane/methanol then n
      butanol/water partitions, and fractionation with Sephadex LH 20 column
      chromatography. Acanthamoebicidal fractions were found to induce the formation of
      large contractile vacuole (LCV) in trophozoites of an Acanthamoeba clinical
      isolate, leading to cell lysis under isotonic and hypotonic conditions within 1
      h. In hypertonic condition, LCV formation was also induced but without cell
      lysis. Acridine orange staining of the treated cells revealed increased
      intracellular acidity, implying an increased proton pumping or a vacuolar proton
      ATPase (V-ATPase) stimulation. Scanning electron microscopy showed cell membrane
      damage with intact cytoplasmic organelles. Our finding has indicated that
      contractile vacuoles of Acanthamoeba trophozoites are the primary target of the
      amoebicidal substance(s) from this endophytic fungus.

PMID- 18633647
TI  - Brain endothelial cells and the glio-vascular complex.
AB  - We present and discuss the role of endothelial and astroglial cells in managing
      the blood-brain barrier (BBB) and aspects of pathological alterations in the BBB.
      The impact of astrocytes, pericytes, and perivascular cells on the induction and
      maintenance of the gliovascular unit is largely unidentified so far. An
      understanding of the signaling pathways that lie between these cell types and the
      endothelium and that possibly are mediated by components of the basal lamina is
      just beginning to emerge. The metabolism for the maintenance of the endothelial
      barrier is intimately linked to and dependent on the microenvironment of the
      brain parenchyma. We report the structure and function of the endothelial cells
      of brain capillaries by describing structures involved in the regulation of
      permeability, including transporter systems, caveolae, and tight junctions. There
      is increasing evidence that caveolae are not only vehicles for endo- and
      transcytosis, but also important regulators of tight-junction-based permeability.
      Tight junctions separate the luminal from the abluminal membrane domains of the
      endothelial cell ("fence function") and control the paracellular pathway ("gate
      function") thus representing the most significant structure of the BBB. In
      addition, the extracellular matrix between astrocytes/pericytes and endothelial
      cells contains numerous molecules with inherent signaling properties that have to
      be considered if we are to improve our knowledge of the complex and closely
      regulated BBB.

PMID- 18633648
TI  - Comparison between entrapment methods for phenol removal and operation of
      bioreactor packed with co-entrapped activated carbon and Pseudomonas fluorescence
      KNU417.
AB  - A microorganism capable of degrading phenol was isolated from crude oil
      contaminated soil and identified as Pseudomonas fluorescence. A porous polymer
      bead of polyvinyl alcohol (PVA) and Xanthan gum was found to be the best
      entrapment for phenol degradation in terms of bead shape (spherical form), bead
      strength, non-agglomeration, phenol degradation rate, and cell holding inside the
      bead. Activated carbon was co-immobilized with the microorganism in the bead,
      which readily adsorbed phenol to decrease initial phenol concentration. Due to
      the decreased phenol concentration, the cells needed shorter adaptation time
      after which the microorganism stably degraded phenol. When the bead containing
      microorganism with 1% of activated carbon was packed in a packed-bed bioreactor,
      the start-up period was shortened by 40 h and the removal efficiency of phenol
      during the period was increased by 28% than the case with only microorganism.

PMID- 18633649
TI  - A gradual update method for simulating the steady-state solution of stiff
      differential equations in metabolic circuits.
AB  - Numerical simulation of differential equation systems plays a major role in the
      understanding of how metabolic network models generate particular cellular
      functions. On the other hand, the classical and technical problems for stiff
      differential equations still remain to be solved, while many elegant algorithms
      have been presented. To relax the stiffness problem, we propose new practical
      methods: the gradual update of differential-algebraic equations based on gradual
      application of the steady-state approximation to stiff differential equations,
      and the gradual update of the initial values in differential-algebraic equations.
      These empirical methods show a high efficiency for simulating the steady-state
      solutions for the stiff differential equations that existing solvers alone cannot
      solve. They are effective in extending the applicability of dynamic simulation to
      biochemical network models.

PMID- 18633650
TI  - The effect of water turbidity on the near-surface water temperature of larval
      habitats of the malaria mosquito Anopheles gambiae.
AB  - Water temperature is an important determinant in many aquatic biological
      processes, including the growth and development of malaria mosquito (Anopheles
      arabiensis and A. gambiae) immatures. Water turbidity affects water temperature,
      as suspended particles in a water column absorb and scatter sunlight and hence
      determine the extinction of solar radiation. To get a better understanding of the
      relationship between water turbidity and water temperature, a series of semi
      natural larval habitats (diameter 0.32 m, water depth 0.16 m) with increasing
      water turbidity was created. Here we show that at midday (1300 hours) the upper
      water layer (thickness of 10 mm) of the water pool with the highest turbidity was
      on average 2.8 degrees C warmer than the same layer of the clearest water pool.
      Suspended soil particles increase the water temperature and furthermore change
      the temperature dynamics of small water collections during daytime, exposing
      malaria mosquito larvae, which live in the top water layer, longer to higher
      temperatures.

PMID- 18633651
TI  - The benefits of prayer on mood and well-being of breast cancer survivors.
AB  - OBJECTIVES: Prayer is becoming more widely acknowledged as a way to cope with
      cancer. The goal of this study was to compare differences in use of prayer
      between breast cancer survivors from different ethnic groups and examine how use
      of prayer is related to mood and quality of life. METHODS: This study used a
      mixed methods design. One hundred and seventy-five breast cancer survivors
      participated in a longitudinal study of survivorship. Women completed in-depth
      qualitative interviews and a battery of measures including quality of life,
      spirituality, social support, and mood. RESULTS: Eighty-one percent of the women
      prayed. There were no significant differences between the groups for any of the
      psychological, social support, or quality of life variables with the exception of
      higher benefit finding and spiritual well-being among those who prayed. The data
      did show that women who prayed were able to find more positive contributions from
      their cancer experience than women who did not pray. The interviews showed that
      those who prayed tended to be African American or Asian, Catholic or Protestant.
      The prayers were for petitioning, comfort, or praise. Some of the women stated
      that they had difficulty praying for themselves. CONCLUSIONS: While there seems
      to be few differences in terms of standardized measures of quality of life,
      social support, and mood between those who prayed and those who did not, the
      interviews showed that certain ethnic minority groups seem to find more comfort
      in prayer, felt closer to God, and felt more compassion and forgiveness than
      Caucasian women.

PMID- 18633652
TI  - Spin-state-dependent oxygen sensitivity of iron dithiolates: sulfur oxygenation
      or disulfide formation.
AB  - The oxygen sensitivity of two related iron(III) dithiolate complexes of the
      ligand [4,7-bis-(2'-methyl-2'-mercatopropyl)-1-thia-4,7-diazacyclononane], (bmmp
      TASN)FeCN (1) and (bmmp-TASN)FeCl (2), has been examined. Oxygen exposure of the
      low-spin complex 1 yields the disulfonate complex (bmmp-O6-TASN)FeCN (3) as an
      olive-green solid with characteristic peaks in the IR spectrum at 1262, 1221,
      1111, 1021, 947, 800, and 477 cm(-1). The corresponding nickel dithiolate, (bmmp
      TASN)Ni (4), yields the related disulfonato derivative, (bmmp-O6-TASN)Ni (5) upon
      addition of H2O2 (IR bands at 1258, 1143, 1106, 1012, 800, and 694 cm(-1). Oxygen
      exposure of the high-spin complex 2 results in disulfide formation and
      decomplexation of the metal with subsequent iron-oxo cluster formation. Complexes
      1 and 2 were examined using density functional theory calculations. A natural
      bond order/natural localized molecular orbital covalency analysis reveals that
      the low-spin complex 1 contains Fe-Sthiolate bonds with calculated covalencies of
      75 and 86%, while the high-spin complex 2 contains Fe-Sthiolate bonds with
      calculated covalencies of 11 and 40%. The results indicate the degree of
      covalency of the Fe-S bonds plays a major role in determining the reaction
      pathway associated with oxygen exposure of iron thiolates. The X-ray structures
      of 1, 4, and 5 are reported.

PMID- 18633653
TI  - Continuous metadynamics in essential coordinates as a tool for free energy
      modelling of conformational changes.
AB  - Modelling of conformational changes in biopolymers is one of the greatest
      challenges of molecular biophysics. Metadynamics is a recently introduced free
      energy modelling technique that enhances sampling of configurational (e.g.
      conformational) space within a molecular dynamics simulation. This enhancement is
      achieved by the addition of a history-dependent bias potential, which drives the
      system from previously visited regions. Discontinuous metadynamics in the space
      of essential dynamics eigenvectors (collective motions) has been proposed and
      tested in conformational change modelling. Here, we present an implementation of
      two continuous formulations of metadynamics in the essential subspace. The method
      was performed in a modified version of the molecular dynamics package GROMACS.
      These implementations were tested on conformational changes in cyclohexane,
      alanine dipeptide (terminally blocked alanine, Ace-Ala-Nme) and SH3 domain. The
      results illustrate that metadynamics in the space of essential coordinates can
      accurately model free energy surfaces associated with conformational changes.

PMID- 18633654
TI  - The 172-kb genomic DNA region of the O. rufipogon yld1.1 locus: comparative
      sequence analysis with O. sativa ssp. japonica and O. sativa ssp. indica.
AB  - Common wild rice (Oryza rufipogon) plays an important role by contributing to
      modern rice breeding. In this paper, we report the sequence and analysis of a 172
      kb genomic DNA region of wild rice around the RM5 locus, which is associated with
      the yield QTL yld1.1. Comparative sequence analysis between orthologous RM5
      regions from Oryza sativa ssp. japonica, O. sativa ssp. indica and O. rufipogon
      revealed a high level of conserved synteny in the content, homology, structure,
      orientation, and physical distance of all 14 predicted genes. Twelve of the
      putative genes were supported by matches to proteins with known function, whereas
      two were predicted by homology to rice and other plant expressed sequence tags or
      complementary DNAs. The remarkably high level of conservation found in coding,
      intronic and intergenic regions may indicate high evolutionary selection on the
      RM5 region. Although our analysis has not defined which gene(s) determine the
      yld1.1 phenotype, allelic variation and the insertion of transposable elements,
      among other nucleotide changes, represent potential variation responsible for the
      yield QTL. However, as suggested previously, two putative receptor-like protein
      kinase genes remain the key suspects for yld1.1.

PMID- 18633655
TI  - Transcript profiling in Vitis riparia during chilling requirement fulfillment
      reveals coordination of gene expression patterns with optimized bud break.
AB  - Endodormant grapevine buds require a period of chilling before they break and
      begin to grow. Custom Vitis bud cDNA microarrays (9,216 features) were used to
      examine gene expression patterns in overwintering Vitis riparia buds during 2,000
      h of 4 degrees C chilling. Three-node cuttings collected concurrently with buds
      were monitored to determine dormancy status. Chilling requirement was fulfilled
      after 1,500 h of chilling; however, 2,000 h of chilling significantly increased
      the rate of bud break. Microarray analysis identified 1,469 significantly
      differentially expressed (p value < 0.05) array features when 1,000, 1,500, and
      2,000 h of chilling were compared to 500 h of chilling. Functional classification
      revealed that the majority of genes were involved in metabolism, cell
      defense/stress response, and genetic information processing. The number of
      significantly differentially expressed genes increased with chilling hour
      accumulation. The expression of a group of 130 genes constantly decreased during
      the chilling period. Up-regulated genes were not detected until the later stages
      of chilling accumulation. Hierarchical clustering of non-redundant expressed
      sequence tags revealed inhibition of genes involved in carbohydrate and energy
      metabolism and activation of genes involved in signaling and cell growth.
      Clusters with expression patterns associated with increased chilling and bud
      break were identified, indicating several candidate genes that may serve as
      indicators of bud chilling requirement fulfillment.

PMID- 18633656
TI  - A comparison of methods for total community DNA preservation and extraction from
      various thermal environments.
AB  - The widespread use of molecular techniques in studying microbial communities has
      greatly enhanced our understanding of microbial diversity and function in the
      natural environment and contributed to an explosion of novel commercially viable
      enzymes. One of the most promising environments for detecting novel processes,
      enzymes, and microbial diversity is hot springs. We examined potential biases
      introduced by DNA preservation and extraction methods by comparing the quality,
      quantity, and diversity of environmental DNA samples preserved and extracted by
      commonly used methods. We included samples from sites representing the spectrum
      of environmental conditions that are found in Yellowstone National Park thermal
      features. Samples preserved in a non-toxic sucrose lysis buffer (SLB), along with
      a variation of a standard DNA extraction method using CTAB resulted in higher
      quality and quantity DNA than the other preservation and extraction methods
      tested here. Richness determined using DGGE revealed that there was some
      variation within replicates of a sample, but no statistical difference among the
      methods. However, the sucrose lysis buffer preserved samples extracted by the
      CTAB method were 15-43% more diverse than the other treatments.

PMID- 18633657
TI  - Decolourization of recalcitrant dyes with a laccase from Streptomyces coelicolor
      under alkaline conditions.
AB  - Colored wastewater from textile industries is a consequence of dye manufacturing
      processes. Two percent of dyes that are produced are discharged directly in
      aqueous effluent and more than 10% are subsequently lost during the textile
      coloration process. It is not surprising that these compounds have become a major
      environmental concern. In that context, we have evaluated the potential use of
      Streptomyces coelicolor laccase for decolourization of various dyes with and
      without a mediator. Results showed that in all cases the combination of laccase
      and the mediator acetosyringone was able to rapidly decolourize, to various
      degrees, all the dyes tested. In 10 min, decolourization was achieved at 94% for
      acid blue 74, 91% for direct sky blue 6b and 65% for reactive black 5.
      Furthermore, decolourization was achieved at 21% for reactive blue 19 and at 39%
      for the direct dye Congo red in 60 min. These results demonstrate the potential
      use of this laccase in combination with acetosyringone, a natural mediator, for
      dye decolourization.

PMID- 18633658
TI  - Role of magnetic resonance methods in the evaluation of prostate cancer: an
      Indian perspective.
AB  - The challenges in detection, localization, and staging of prostate cancer have
      prompted the investigation of the role of various magnetic resonance (MR)
      methodologies in a large cohort of men prior to biopsy. The identification of
      suspicious areas of malignancy was carried out using magnetic resonance imaging
      (MRI), magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted
      imaging (DWI). Our data shows that apparent diffusion coefficient (ADC) may be a
      reliable marker to differentiate normal, benign, and malignant prostate tissues
      similar to the metabolite ratio. Also, the combined use of MRSI and DWI improves
      the diagnosis of prostate cancer. In this review, we present our experience on
      the use of MRI, MRSI and DWI methods in the assessment of prostate cancer in
      Indian men. Further, analysis of the comparison of the ADC and the metabolite
      ratio values reported in the literature across various patient populations are
      presented.

PMID- 18633660
TI  - On the correlation between T(2) and tissue diffusion coefficients in exercised
      muscle: quantitative measurements at 3T within the tibialis anterior.
AB  - PURPOSE: To assess the transverse relaxation time T(2) and diffusion coefficient
      D before and following exercise in the tibialis anterior muscle and determine
      whether T(2) and D values were correlated. METHODS: Measurements of T(2) and D
      were performed at 3 T within axial slices through the calf muscles of six healthy
      volunteers at 95 s intervals before and for 10-12 min after a dorsiflexion
      exercise to exhaustion. RESULTS: The mean +/- standard deviation (SD) of T(2) and
      D before exercise were 32 +/- 1.55 ms and 1.52 +/- 0.15 mum(2)/ms, and after
      exercise were 43 +/- 2.5 ms and 1.72 +/- 0.13 mum(2)/ms, respectively. The mean
      +/- SD inter-individual recovery times of the % change in T(2) and D after
      exercise were 7.9 +/- 4.2 and 10.9 +/- 7.0 min, respectively. The T(2) and D
      values showed a significant correlation throughout the experiments (r (2) =
      0.45). CONCLUSIONS: The increase in T(2) of skeletal muscle after exercise is
      correlated with the increase of the diffusion coefficient D and the recovery
      times appear similar, indicating that any model used to explain T(2) increases
      with exercise must also account for increased diffusion coefficients.

PMID- 18633659
TI  - Two-dimensional MR spectroscopy of healthy and cancerous prostates in vivo.
AB  - OBJECTIVES: A major goal of this article is to summarize the current status of
      evaluating prostate metabolites non-invasively using spatially resolved two
      dimensional (2D) MR Spectroscopy (MRS). MATERIALS AND METHODS: Due to various
      technical challenges, the spatially resolved versions of 2D MRS techniques are
      currently going through the developmental stage. During the last decade, four
      different versions of 2D MRS sequences have been successfully implemented on 3T
      and 1.5T MRI scanners manufactured by three different vendors. These sequences
      include half and maximum echo sampled J-resolved spectroscopy (JPRESS), S-PRESS
      and L-COSY, which are single volume localizing sequences, and the multi-voxel
      based JPRESS sequence. RESULTS: Even though greater than 1ml voxels have been
      used, preliminary evaluations of 2D JPRESS, S-PRESS and L-COSY sequences have
      demonstrated unambiguous detection of citrate, creatine, choline, spermine and
      more metabolites in human prostates. ProFIT-based quantitation of JPRESS and L
      COSY data clearly shows the superiority of 2D MRS over conventional one
      dimensional (1D) MRS and more than six metabolites have been successfully
      quantified. These sequences have been evaluated in a small group of prostate
      pathologies and pilot investigations using these sequences show promising results
      in prostate pathologies. CONCLUSION: Implementation of the state-of-the-art 2D
      MRS techniques and preliminary evaluation in prostate pathologies are discussed
      in this review. Even though these techniques are going through developmental and
      early testing phases, it is evident that 2D MRS can be easily added on to any
      clinical Magnetic Resonance Imaging (MRI) protocol to non-invasively record the
      biochemical contents of the prostate.

PMID- 18633661
TI  - EIT image reconstruction with four dimensional regularization.
AB  - Electrical impedance tomography (EIT) reconstructs internal impedance images of
      the body from electrical measurements on body surface. The temporal resolution of
      EIT data can be very high, although the spatial resolution of the images is
      relatively low. Most EIT reconstruction algorithms calculate images from data
      frames independently, although data are actually highly correlated especially in
      high speed EIT systems. This paper proposes a 4-D EIT image reconstruction for
      functional EIT. The new approach is developed to directly use prior models of the
      temporal correlations among images and 3-D spatial correlations among image
      elements. A fast algorithm is also developed to reconstruct the regularized
      images. Image reconstruction is posed in terms of an augmented image and
      measurement vector which are concatenated from a specific number of previous and
      future frames. The reconstruction is then based on an augmented regularization
      matrix which reflects the a priori constraints on temporal and 3-D spatial
      correlations of image elements. A temporal factor reflecting the relative
      strength of the image correlation is objectively calculated from measurement
      data. Results show that image reconstruction models which account for inter
      element correlations, in both space and time, show improved resolution and noise
      performance, in comparison to simpler image models.

PMID- 18633662
TI  - Surface EMG and acceleration signals in Parkinson's disease: feature extraction
      and cluster analysis.
AB  - We present an advanced method for feature extraction and cluster analysis of
      surface electromyograms (EMG) and acceleration signals in Parkinson's disease
      (PD). In the method, 12 different EMG and acceleration signal features are
      extracted and used to form high-dimensional feature vectors. The dimensionality
      of these vectors is then reduced by using the principal component approach.
      Finally, the cluster analysis of feature vectors is performed in a low
      dimensional eigenspace. The method was tested with EMG and acceleration data of
      42 patients with PD and 59 healthy controls. The obtained discrimination between
      patients and controls was promising. According to clustering results, one cluster
      contained 90% of the healthy controls and two other clusters 76% of the patients.
      Seven patients with severe motor dysfunctions were distinguished in one of the
      patient clusters. In the future, the clinical value of the method should be
      further evaluated.

PMID- 18633663
TI  - Regional differences in hip bone mineral density levels in Norway: the NOREPOS
      study.
AB  - SUMMARY: Large regional differences in hip fracture rates within Norway have
      previously been shown. However, regional differences in hip bone mineral density
      (BMD) have not yet been assessed. In this study including 10,504 hip scans, there
      were significant regional differences in BMD. Further studies to address reasons
      for the regional differences in hip fracture risk are warranted. INTRODUCTION:
      Bone mineral density (BMD) at the hip is an important determinant of hip
      fracture. While regional differences in Norwegian hip fracture rates have
      previously been shown, no comparative studies of hip BMD have been conducted.
      METHODS: Total hip BMD was measured by DXA in two population-based studies across
      Norway during 1997-2002. Valid hip scans with in vivo calibration were obtained
      from 5127 subjects in Tromso (age 30-89 years) and 5377 subjects in Bergen (age
      47-50 and 71-75 years). RESULTS: Women >or=60 years in Tromso had 0.052 g/cm(2)
      higher age-adjusted BMD than women in Bergen, whereas BMD among women <60 years
      was similar in Tromso and Bergen. Age-adjusted total hip BMD was 0.035 g/cm(2)
      lower in men >or=60 years in Bergen compared with Tromso, and the corresponding
      figure for men <60 years was 0.028 g/cm(2). While adjustment for body mass index
      explained some, but not all of the differences, smoking, physical activity,
      diabetes prevalence, self-perceived health, intake of alcohol and estrogen use
      did not. CONCLUSIONS: Regional differences in BMD at the hip were found in
      Norway. Reasons for this and potential impact on hip fracture rates should be
      explored in further studies.

PMID- 18633664
TI  - Special report on the 2007 adult and pediatric Position Development Conferences
      of the International Society for Clinical Densitometry.
AB  - The International Society for Clinical Densitometry (ISCD) conducts Position
      Development Conferences (PDCs) for the purpose of establishing standards and
      guidelines in the field of bone densitometry. Topics for consideration are
      selected according to clinical relevance, a perceived need for standardization,
      and the likelihood of achieving agreement. Questions regarding nomenclature,
      indications, acquisition, analysis, quality control, interpretation, and
      reporting of bone density tests for each topic area are assigned to task forces
      for a comprehensive review of the scientific literature. The findings of the
      review and recommendations are then presented to an international panel of
      experts at the PDC. The expert panel votes on potential Official Positions for
      appropriateness, necessity, quality of the evidence, strength of the
      recommendation, and applicability (worldwide or variable according to local
      requirements). Recommendations that are approved by the ISCD Board of Directors
      become Official Positions. The first Pediatric PDC was 20-21 June 2007 in
      Montreal, QC, Canada. The most recent Adult PDC was held 20-22 July 2007, in
      Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD
      PDCs and presents selected Official Positions of general interest.

PMID- 18633665
TI  - Weight and body mass index predict bone mineral density and fractures in women
      aged 40 to 59 years.
AB  - Weight and body mass index are associated with low bone mineral density and
      fractures in older women. This retrospective cohort study confirms a similar
      relationship in women aged 40 to 59 years. INTRODUCTION: Risk factors for the
      prediction of osteoporosis and fractures have been less thoroughly studied in
      younger women. We evaluated the associations between weight, body mass index
      (BMI), the Osteoporosis Self-Assessment Tool (OST), bone mineral density (BMD)
      and fracture risk in women aged 40 to 59 years. METHODS: Using administrative
      health management databases, we conducted a retrospective cohort study in 8,254
      women aged 40-59 years who had baseline BMD testing. Linear regression and Cox
      proportional multivariate models were created to examine the associations with
      weight, BMI, OST, BMD, and subsequent fractures throughout a 3.3-year follow-up.
      RESULTS: Body weight, BMI, and OST had a similar overall performance in their
      ability to classify women with femoral neck T-score < or = -2.5. Throughout
      27,256 person years of observation, 225 women experienced one or more fractures.
      After adjustment for age, prevalent fractures, and use of corticosteroids, each
      standard deviation decrease in weight was associated with a 19% increase in the
      risk of incident fracture (95% CI: 1.01-1.35). Femoral neck BMD and the presence
      of prevalent fractures were also associated with the risk of incident fractures.
      CONCLUSIONS: Low weight and BMI predict osteoporosis and are associated with
      increased fracture risk in younger women. The negative impact of low body weight
      on bone health should be more widely recognized.

PMID- 18633666
TI  - Management of osteoporosis in primary care in Australia.
AB  - This study reviewed factors influencing osteoporosis management in primary care
      settings in Australia and examined risk profiles of patients (n = 37,957) for
      osteoporosis. Only 29.7% of patients with a prior fracture were currently on
      specific medication for osteoporosis. The results highlight the need for further
      exploration of barriers to osteoporosis management. INTRODUCTION: Osteoporosis
      management in primary care is suboptimal even for high-risk people with a history
      of prior fracture. METHODS: This study reviewed factors influencing the
      management of individuals at risk for osteoporosis in primary care settings in
      Australia and examined risk profiles of patients for osteoporosis. Patients (n =
      37,957, mean age 71) were recruited over a 12-month period (February 2006-Jan
      2007) and interviewed. RESULTS: With regard to risk factors for osteoporosis,
      12.6% of patients reported a history of prior minimal trauma fracture, 7.5%
      reported a family history of osteoporosis, 7.4% reported they were current
      smokers, 11.4% reported low dietary calcium intake, 31.8% reported no regular
      weekly physical exercise and 10.3% reported current use of glucocorticoids. Of
      those with a prior fracture, only 29.7% were currently on specific medication for
      osteoporosis. Radiography (n = 17,754) demonstrated a prior vertebral fracture in
      30.1%, but only 3.8% of the 17,754 patients reported current use of specific
      osteoporosis medication. CONCLUSIONS: This study has confirmed low rates of
      treatment in primary care even in individuals who have already suffered a prior
      fracture or have other risk factors. This study highlights the need for further
      exploration of barriers to osteoporosis management in the primary care setting.

PMID- 18633667
TI  - Recent trends in the incidence and lifetime risk of hip fracture in Tottori,
      Japan.
AB  - SUMMARY: Hip fracture incidence from 2004 to 2006 in the Tottori prefecture of
      Japan was investigated and compared with previously reported rates. The age- and
      gender-specific incidence of hip fracture in the Tottori prefecture has not
      plateaued, as has been reported for populations in Northern Europe or North
      America. INTRODUCTION: Recent data from Northern Europe and North America
      indicate that the incidence of hip fracture has plateaued, whereas most reports
      from Asia indicate that the incidence is increasing. The aims of this study were
      to investigate the recent incidence of hip fracture in the Tottori prefecture,
      Japan, and to compare it with previous reports. METHODS: All hip fractures in
      patients aged 35 years and older occurring between 2004 and 2006 were surveyed in
      all of the hospitals from the Tottori prefecture. The age- and gender-specific
      incidence rates were then calculated. Using these and previously reported data,
      the estimated number of hip fracture patients was determined using the age- and
      gender-specific incidence rates in each year from 1986 to 2006. RESULTS: The
      survey identified 851, 906, and 1,059 patients aged 35 years and older, in 2004,
      2005, and 2006 respectively. The residual lifetime risk of hip fracture for
      individuals at 50 years of age was estimated to be 5.6% for men and 20.0% for
      women. The estimated number of patients from 1986 to 2006 showed a significant
      increase over time for both genders. CONCLUSIONS: The age- and gender-specific
      incidence of hip fracture in the Tottori prefecture, Japan has not plateaued for
      either gender.

PMID- 18633668
TI  - Physical activity and dietary calcium interactions in bone mass in Scottish
      postmenopausal women.
AB  - In this population-based cohort of 1,254 older Scottish women we found
      significant interactions between the mechanical component of self-reported
      habitual physical activity (PA) and dietary calcium (Ca) in BMD, independent of
      other risk factors. At low and/or medium Ca intakes BMD was higher amongst the
      most active people. INTRODUCTION: Although there is general agreement that
      increased activity (PA) and dietary calcium (Ca) consumption may help maintain
      bone mass in later life and prevent fractures, the amount required remains
      uncertain. METHODS: In 2001-2003, 1,847 postmenopausal women (mean +/- SD age:
      69.3 +/- 5.5 years) underwent bone mineral density (BMD) measurement and, in
      2004, 68.7% (n = 1,254) completed a bone-specific Physical Activity Questionnaire
      (bsPAQ) and a food frequency questionnaire. The bsPAQ measures the metabolic and
      mechanical components of PA. Interactions of PA and Ca in BMD were examined using
      ANCOVA. RESULTS: Significant interactions were identified in the BMD of the
      lumbar spine (LS), right hip (RH) and left hip (LH), after adjustment for
      confounders, between tertiles of PA classified according to the mechanical
      component and tertiles of energy-adjusted Ca intake (ANCOVA p = 0.006, p = 0.004
      and p = 0.013 respectively). For example, at medium Ca intakes LH BMD was higher
      by 7.8% in the highest tertile of PA compared with the lowest tertile of PA.
      CONCLUSIONS: These data suggest that health promotion campaigns to increase PA
      would be most effective in populations with a low/medium calcium intake.

PMID- 18633669
TI  - Diagnosis of new onset heart failure in the community: the importance of a shared
      care approach and judicious use of BNP.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) may help general practitioners (GPs)
      to "rule-out" heart failure (HF) and reduce referral burden on specialist
      assessment clinics. AIMS: To determine the diagnostic value of BNP in HF
      referrals by GPs to a specialist unit. METHODS: From 2003 to 2007, 327 GP
      referrals were made to a HF new patient diagnostic clinic (NDC) with a
      provisional diagnosis of HF. The NDC provides rapid assessment of potential HF
      patients and ensures appropriate therapy and follow-up for those with a confirmed
      diagnosis. HF diagnosis was confirmed by the Framingham criteria. RESULTS: HF was
      present in 39% of cases referred (mean age 75 +/- 10 years, 49% male). The
      inclusion of BNP as a "rule-out" test with a cut-off value of 100 pg/mL would
      have reduced the number of patients originally referred to the NDC by 175.
      However, this would have resulted in delayed diagnosis and treatment of 20 (16%)
      "false-negative" patients. CONCLUSIONS: Availability of BNP to GPs would improve
      referral patterns but with high risk of delayed diagnosis. The data underline the
      need for a shared-care approach to the new diagnosis of HF.

PMID- 18633670
TI  - Whole-grain cereal products based on a high-fibre barley or oat genotype lower
      post-prandial glucose and insulin responses in healthy humans.
AB  - BACKGROUND: Several factors can affect glycemic and insulinemic responses from
      cereal foods. Some suggested factors lowering the responses are; intact botanical
      structure, high amylose/high ss-glucan cereal varieties, organic acid produced
      during fermentation and food processes inducing retrogradation of starch. AIM OF
      THE STUDY: To evaluate the impact of fermented whole grain cereal kernels with
      high content of amylose (40%) and/or beta-glucan (4.6%) on postprandial glucose
      and insulin responses in healthy adults. METHODS: Thirteen healthy volunteers (4
      men and 9 women) were given 25 g available carbohydrate portions of: glucose
      solution; tempe fermented whole-grain barley and tempe fermented whole-grain oat.
      Blood samples were collected directly before the meal (fasting) and 15, 30, 45,
      60, 90 and 120 min after the start of the meal. The GI (glycemic index) and II
      (insulin index) of meals were calculated for each subject according to FAO/WHO
      standards. RESULTS: Peak glucose response was lowest after the tempe meal with
      high-amylose/ high-ss-glucan barley tempe while insulin response was lowest after
      the meal with high beta-glucan oat tempe. The mean blood glucose responses for
      both the barley and the oat tempe meals were significantly lower than from the
      reference glucose load (P < 0.0001) during the first 60 min. The calculated GI:s
      for barley and oat tempe were 30 and 63, respectively. Mean serum insulin
      responses from barley and oat tempe were significantly lower compared with the
      glucose load (P < 0.002) during the first 60 min, and the calculated II was lower
      for oat tempe (21) compared with barley tempe (55). CONCLUSIONS: The results
      suggest that cereal products with beneficial influence on postprandial plasma
      glucose and insulin responses can be tailored by fermentation and enclosure of
      high-amylose and/or high-beta-glucan barley and oat kernels.

PMID- 18633671
TI  - Entirely laparoscopic radical gastrectomy for adenocarcinoma: lymph node yield
      and resection margins.
AB  - BACKGROUND: Laparoscopic assisted distal gastrectomy for adenocarcinoma has been
      widely reported from Japan and Korea but there are sparse data for Western
      patients. This study aimed to describe and compare the perioperative outcomes and
      pathological staging for consecutive patients who underwent laparoscopic or open
      gastrectomy by a single surgeon in the UK. METHODS: During the period from April
      2005 to May, 2007, patients with gastric adenocarcinoma were selected for open or
      laparoscopic resection at the discretion of the surgeon. Gastric resections for
      gastrointestinal stromal tumour (GIST) or benign disease were excluded.
      Laparoscopic gastrectomy was performed entirely laparoscopically with
      intracorporeal anastomosis, followed by specimen retrieval via a suprapubic
      incision. RESULTS: There were 21 men and 8 women, median age 75 years (range 45
      88 years), with American Anaesthesiology Association scores of 3 or 4 in 19
      patients. Gastrectomy was performed laparoscopically in 18 patients (62%; total
      gastrectomy, 6 patients) or open in 11 patients (total gastrectomy, 7). Five
      laparoscopic gastrectomies were converted to open procedures, three patients had
      re-laparoscopy and one patient had subsequent laparotomy. As compared with open
      gastrectomy, laparoscopic resection had longer operation time and similar length
      of hospital stay. There was one postoperative mortality in each group. There was
      similar lymph node retrieval for laparoscopic or open resection [23 (range 10-44)
      versus 26 (8-95), respectively; p = 0.40], with inadequate lymphadenectomy (<15
      nodes) in two laparoscopic cases and one open case. R1 resection was limited to
      patients with pT3 disease (laparoscopic, 4; open, 2). CONCLUSIONS: Perioperative
      outcomes were similar for laparoscopic or open gastrectomy. Lymphadenectomy was
      adequate in 89% of laparoscopic gastrectomies. pT3 tumours were at risk of
      noncurative resection, as described in large Western series of open gastrectomy.

PMID- 18633672
TI  - Laparoscopic and open reversal of Hartmann's procedure--a comparative
      retrospective analysis.
AB  - BACKGROUND: Restoration of intestinal continuity after Hartmann's procedure has
      traditionally required laparotomy. This study compares our experience with
      laparoscopic and open reversal of Hartmann's procedure. STUDY DESIGN: All
      laparoscopic and open Hartmann's reversal procedures performed between January
      1998 and June 2006 were reviewed. Patients with laparoscopic reversal were
      retrospectively matched by age, body mass index (BMI), and indication to controls
      with open reversal. Demographic data, perioperative course, and postoperative
      complications were documented. RESULTS: We identified 41 patients who underwent
      laparoscopic reversal of Hartmann's procedure and these were matched to 41
      patients with open reversal. The groups had similar average age and BMI. The
      predominant indication for surgery in both groups was diverticular disease.
      Conversion to laparotomy occurred in eight patients (19.5%), and was due to dense
      adhesions or difficulty in identification of the rectal stump. Adhesions were
      significantly greater in the conversion group (p <0.05), and the rectal stump was
      not marked in any of these cases. The most common short-term complications were
      ileus and surgical site infection. There were no anastomotic leaks and no
      mortalities. The mean operative times in the laparoscopic and open groups were
      193 versus 209 min, respectively (p = 0.33). The laparoscopic group had a
      significantly lower estimated blood loss of 166 versus 326 mL (p < 0.0005),
      shorter time to bowel function return (4.1 versus 5.2 days, p < 0.05), and a
      shorter hospital stay (6.4 versus 8.0 days, p < 0.05). The major complication
      rate was also significantly lower in the laparoscopic group than in the open
      group (4.8% versus 12.1%, p < 0.05). CONCLUSIONS: Laparoscopic reversal of
      Hartmann's procedure is a safe and practical alternative to open reversal. It can
      be performed with similar operative time, fewer complications, and a faster
      recovery time. Conversion during the reversal procedure was significantly
      impacted by severity of adhesions and marking of the rectal stump.

PMID- 18633674
TI  - Negative serum carcinoembryonic antigen has insufficient accuracy for excluding
      recurrence from patients with Dukes C colorectal cancer: analysis with likelihood
      ratio and posttest probability in a follow-up study.
AB  - PURPOSE: This study was designed to determine the efficacy of carcinoembryonic
      antigen (CEA) monitoring for screening patients with colorectal cancer by using
      posttest probability of recurrence. METHODS: For this study, 348 (preoperative
      serum CEA level elevated: CEA+, n = 119; or normal: CEA-, n = 229) patients who
      had undergone potentially curative surgery for colorectal cancer were enrolled.
      After five-year follow-up with measurements of serum CEA levels and imaging
      workup, posttest probabilities of recurrence were calculated. RESULTS: Recurrence
      was observed in 39 percent of CEA+ patients and 30 percent in CEA- patients, and
      CEA levels were elevated in 33.3 percent of CEA+ patients and 17.5 percent of CEA
      patients. With obtained sensitivity (68.4 percent, CEA+; 41 percent, CEA-),
      specificity (83 percent, CEA+; 91 percent, CEA-) and likelihood ratio (test
      positive: 4.0, CEA+; 4.4, CEA-; and test negative: 0.38, CEA+; 0.66, CEA-),
      posttest probability given the presence of CEA elevation in the CEA+ and CEA- was
      72.2 and 65.5 percent, respectively, and that given the absence of CEA elevation
      was 20 and 22.2 percent, respectively. CONCLUSIONS: Whereas postoperative CEA
      elevation indicates recurrence with high probability, a normal postoperative CEA
      is not useful for excluding the probability of recurrence.

PMID- 18633675
TI  - Therapeutic potential of two probiotics in inflammatory bowel disease as observed
      in the trinitrobenzene sulfonic acid model of colitis.
AB  - PURPOSE: The pathogenesis of inflammatory bowel disease is thought to be a
      multifactorial process. One of the leading hypotheses is that an imbalance in
      normal gut flora induces an excessive immune response and contributes to
      inflammation in the gastrointestinal tract. Administration of probiotic bacteria
      reduces symptoms in patients suffering from inflammatory bowel diseases, probably
      via both manipulation of the microflora and stimulation of the intestinal immune
      system. In the current study the therapeutic potential of two different
      probiotics-Lactobacillus GG and a mixture of Streptococcus thermophilus,
      Lactobacillus acidophilus, and Bifidobacterium longum (YO-MIX Y 109 FRO 1000)--in
      a rat model of colitis were evaluated. METHODS: Male Wistar rats were
      administered probiotics for three days simultaneously with colitis induction.
      Colonic damage was evaluated histologically and biochemically and colonic
      tissues, as well as fecal samples, were used for bacterial studies using 16S rRNA
      gene primers. RESULTS: Probiotics administration reduced the relative amounts of
      the pathogenic bacteria Aeromonas and Escherichia coli in the colonic tissue.
      However, whereas both probiotics affected colon morphology, only Lactobacillus GG
      administration reduced myeloperoxidase activity. CONCLUSIONS: We report the
      therapeutic rather than preventive potential of two different probiotics in an
      animal model of colitis.

PMID- 18633676
TI  - The effectiveness of hyaluronan-carboxymethylcellulose membrane in different
      severity of adhesions observed at the time of relaparotomies: an experimental
      study on mice.
AB  - PURPOSE: This study was designed to evaluate the effect of Seprafilm use in the
      presence of different severity of adhesions encountered in relaparotomies.
      METHODS: A total of 110 male Balb/c mice were randomized into two experiment
      groups: Sepra and Control. All animals underwent cecal and small-bowel abrasions
      during the first operation. The severity of adhesions were evaluated as "slight"
      or"dense" at the time of relaparotomy performed 14days after the initial
      operation, and Seprafilm was applied to the animals in Group Sepra. Accordingly,
      the groups were documented as Sepra-slight, Sepra-dense, Control-slight, and
      Control-dense. All subjects were killed 14days later, the adhesion severity was
      evaluated with a scale scoring 0 to 5, and the results were compared between the
      groups. RESULTS: The death of 21 animals (19.1 percent) before (n = 10) and after
      (n = 11) the second operation left 22, 24, 26, and 17 animals in groups Sepra
      slight, Sepra-dense, Control-slight, and Control-dense, respectively. Seprafilm
      significantly reduced the adhesion severity score (1.1 +/- 1.1 vs. 2.1 +/- 1.5 in
      Groups Sepra and Control, respectively; P < 0.05). Seprafilm did not
      significantly decrease the severity of adhesions in the presence of slight
      adhesions at the time of relaparotomy (P > 0.05). However, the analysis of groups
      revealed that Seprafilm was more effective when used during the observation of
      severe adhesions at the time of relaparotomy (1.7 +/- 1.4 vs. 2.7 +/- 1.5 in
      Groups Sepra-dense vs. Control-dense, respectively; P < 0.05). CONCLUSIONS:
      Seprafilm is effective in preventing adhesions even if it is used at the time of
      relaparotomy, but the antiadhesive effect of product peaks when it is used during
      the observation of dense adhesions at the time of relaparotomy.

PMID- 18633677
TI  - Decreased expression of monocyte chemoattractant protein-1 predicts poor
      prognosis following curative resection of colorectal cancer.
AB  - PURPOSE: The significance of monocyte chemoattractant protein-1 in colorectal
      cancer is not well understood. The aim of this study was to investigate the
      significance of monocyte chemoattractant protein-1 expression in colorectal
      cancer patients undergoing potentially curative surgery. METHODS: We studied 101
      colorectal cancer patients who underwent potentially curative surgery. The
      concentration of monocyte chemoattractant protein-1 in the tumor and normal
      mucosa were measured. The expression of monocyte chemoattractant protein-1 was
      also evaluated immunohistochemically. RESULTS: The tissue concentration of
      monocyte chemoattractant protein-1 in the tumor was significantly higher than
      that in the normal mucosa. The decreased monocyte chemoattractant protein-1
      cancer/normal ratio was associated with lymph node involvement and could predict
      poor prognosis. On univariate analysis, the decreased monocyte chemoattractant
      protein-1 ratio, carcinoembryonic antigen levels, and serosal invasion were the
      significant factors for poor prognosis. Multivariate analysis showed that
      monocyte chemoattractant protein-1 ratio was the only independent risk factor
      predictive of a poor prognosis. Immunohistochemically, monocyte chemoattractant
      protein-1 was expressed in the cytoplasm. CONCLUSION: The decreased monocyte
      chemoattractant protein-1 ratio was an independent factor predicting poor
      prognosis in patients undergoing potentially curative surgery. Monocyte
      chemoattractant protein-1 deficiency may present a new therapeutic approach for
      colorectal cancer.

PMID- 18633678
TI  - Successful treatment of mucosa-associated lymphoid tissue lymphoma of the rectum
      with radiation therapy: report of a case.
AB  - We report a case of Stage IE mucosa-associated lymphoid tissue lymphoma arising
      in the rectum, which was successfully treated with radiotherapy. A 60-year-old
      man had several months of altered bowel habit with rectal bleeding and was found
      to have a large rectal tumor with no evidence of distant spread. Histologic
      studies showed this to be a mucosa-associated lymphoid tissue lymphoma. The
      patient received 45 Gy in 25 fractions with external beam radiotherapy during 5
      weeks. The treatment was well tolerated and review at 41 months revealed no
      evidence of recurrence.

PMID- 18633679
TI  - Prognostic analysis of rectal stromal tumors by reference of National Institutes
      of Health risk categories and immunohistochemical studies.
AB  - PURPOSE: Prognostic analysis of stromal tumors focusing on the rectal area is
      rarely performed. This study elucidated prognostic factors by referencing
      biomarkers of Ki67 and p53. METHODS: Forty-nine surgically resected rectal
      stromal tumors were collected from 1986 to 2006. Immunohistochemical studies were
      performed with antibodies of CD117, CD34, smooth muscle actin, desmin, S100,
      Ki67, and p53. RESULTS: The immunoreactivities were: CD34, 83.6 percent; smooth
      muscle actin, 28.5 percent; S100, 4.1 percent; desmin,16.3 percent;, Ki67, 30.6
      percent;, and p53 34.7 percent. Both p53+ and Ki67+ tumors were associated with
      increased tumor mitosis, increased tumor size, nonspindle cell type, and
      increased cell pleomorphism (P < 0.05). Increased National Institutes of Health
      risk was associated with old age, nonspindle cell types, and severe nuclear
      pleomorphism (P < 0.05). Survival analysis demonstrated that older patients (P =
      0.0039), large tumor size (P = 0.003), high mitotic count (P < 0.001), increased
      risk categories (P < 0.001), high cell pleomorphism (P = 0.003), p53+ (P =
      0.007), and Ki67 + (P = 0.002) were prognostic factors for poor disease-free
      survival. An independent prognostic factor was tumor mitotic count. CONCLUSIONS:
      This study demonstrated the prognostic role of Ki67 and p53 in rectal stromal
      tumors. Notably, tumor mitosis was superior for prognostic prediction compared to
      National Institutes of Health risk categories.

PMID- 18633680
TI  - Changes in medical students' attitudes towards end-of-life decisions across
      different years of medical training.
AB  - BACKGROUND: Decisions to forgo life-sustaining medical treatments in terminally
      ill patients are challenging, but ones that all doctors must face. Few studies
      have evaluated the impact of medical training on medical students' attitudes
      towards end-of-life decisions and none have compared them with an age-matched
      group of non-medical students. OBJECTIVE: To assess the effect of medical
      education on medical students' attitudes towards end-of-life decisions in acutely
      ill patients. DESIGN: Cross-sectional study. PARTICIPANTS: Four hundred and two
      students at The Chinese University of Hong Kong. MEASUREMENTS: Completion of a
      questionnaire focused on end-of-life decisions. MAIN RESULTS: The number of
      students who felt that cardiopulmonary resuscitation must always be provided was
      higher in non-medical students (76/90 (84%)) and medical students with less
      training (67/84 (80%) in year 1 vs. 18/67 (27%) in year 5) (p < 0.001).
      Discontinuing life-support therapy was more accepted among senior medical
      students compared to junior medical and non-medical students (27/66 (41%) in year
      5 vs. 18/83 (22%) in year 1 and 20/90 (22%) in non-medical students) (p = 0.003).
      An unexpectedly large proportion of non-medical students (57/89 (64%)) and year 1
      medical students (42/84 (50%)) found it acceptable to administer fatal doses of
      drugs to patients with limited prognosis. Euthanasia was less accepted with more
      years of training (p < 0.001). When making decisions regarding limitation of life
      support therapy, students chose to involve patients (98%), doctors (92%) and
      families (73%) but few chose to involve nurses (38%). CONCLUSIONS: Medical
      students' attitudes towards end-of-life decisions changed during medical training
      and differed significantly from those of non-medical students.

PMID- 18633682
TI  - Assessing the acute abdomen in the bariatric patient: need for improvement.

PMID- 18633683
TI  - The imaging evaluation of cholelithiasis in the obese patient-ultrasound vs CT
      cholecystography: our experience with the bariatric surgery population.
AB  - BACKGROUND: The purpose of this study was to compare computed tomography (CT)
      cholecystography and ultrasound for gallstone detection in preoperative bariatric
      surgery patients. METHODS: The study included 16 asymptomatic prebariatric
      surgery patients. On the same day, each patient underwent abdominal CT 4 h after
      IV cholecystograffin injection, and gallbladder ultrasound. CT and ultrasounds
      were reviewed by two independent, blinded radiologists, and scored as follows: no
      gallstones, possible gallstones, definite gallstones, indeterminate. CT and
      ultrasound results were compared. RESULTS: Ultrasound detected definite
      gallstones in three patients, possible gallstones in one patient, and no
      gallstones in ten patients. Two scans were considered indeterminate. CT
      cholecystography detected definite gallstones in six patients, possible
      gallstones in zero patients, and no gallstones in nine patients, and was
      indeterminate in one patient. All three patients with gallstones seen
      sonographically had definite gallstones on CT. The patient with possible
      gallstones detected sonographically had definite stones detected at CT. One of
      the two patients with indeterminate ultrasounds had gallstones detected at CT.
      The other patient had both studies indeterminate. One patient with no gallstones
      sonographically had definite gallstones at CT. No patients with a negative CT had
      gallstones seen on ultrasound. Nine patients had no gallstones on either
      modality. CONCLUSIONS: CT cholecystography is more sensitive and specific for the
      detection of gallstones in the obese population. CT cholecystography should be
      considered in place of ultrasound in the preoperative workup of these patients.

PMID- 18633684
TI  - Orthopaedic clinical officer program in Malawi: a model for providing orthopaedic
      care.
AB  - Malawi has a population of about 13 million people, 85% of whom live in rural
      areas. The gross national income per capita is US$620, with 42% of the people
      living on less than US$1 per day. The government per capita expenditure on health
      is US$5. Malawi has 266 doctors, of whom only nine are orthopaedic surgeons. To
      address the severe shortage of doctors, Malawi relies heavily on paramedical
      officers to provide the bulk of healthcare. Specialized orthopaedic clinical
      officers have been trained since 1985 and are deployed primarily in rural
      district hospitals to manage 80% to 90% of the orthopaedic workload in Malawi.
      They are trained in conservative management of most common traumatic and
      nontraumatic musculoskeletal conditions. Since the program began, 117 orthopaedic
      clinical officers have been trained, of whom 82 are in clinical practice. In
      2002, Malawi began a local orthopaedic postgraduate program with an intake of one
      to two candidates per year. However, orthopaedic clinical officers will continue
      to be needed for the foreseeable future. Orthopaedic clinical officer training is
      a cost-effective way of providing trained healthcare workers to meet the
      orthopaedic needs of a country with very few doctors and even fewer orthopaedic
      surgeons.

PMID- 18633685
TI  - The use of theory in health behavior research from 2000 to 2005: a systematic
      review.
AB  - BACKGROUND: Theory-based health behavior change programs are thought to be more
      effective than those that do not use theory. No previous reviews have assessed
      the extent to which theory is used (that is, operationalized and tested) in
      empirical research. PURPOSE: The purpose of this study was to describe theory use
      in recent health behavior literature and to assess the proportion of research
      that uses theory along a continuum from: informed by theory to applying, testing,
      or building theory. METHODS: A sample of empirical research articles (n = 193)
      published in ten leading public health, medicine, and psychology journals from
      2000 to 2005 was coded to determine whether and how theory was used. RESULTS: Of
      health behavior articles in the sample, 35.7% mentioned theory. The most-often
      used theories were The Transtheoretical Model, Social Cognitive Theory, and
      Health Belief Model. Most theory use (68.1%) involved research that was informed
      by theory; 18% applied theory; 3.6% tested theory; and 9.4% sought to build
      theory. CONCLUSIONS: About one third of published health behavior research uses
      theory and a small proportion of those studies rigorously apply theory. Patterns
      of theory use are similar to reports from the mid-1990s. Behavioral researchers
      should strive to use theory more thoroughly by applying, testing, and building
      theories in order to move the field forward.

PMID- 18633686
TI  - Immunohistochemical localization of GABA, GAD65, and the receptor subunits
      GABAAalpha1 and GABAB1 in the zebrafish cerebellum.
AB  - Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in
      the central nervous system. Its role is especially prominent in the cerebellum,
      where most neuron types are GABAergic. However, little is known about its
      function in the cerebellum of teleost fish, which is only partly homologous to
      its mammalian counterpart. Here, we investigated the expression and distribution
      of GABA, the GABA-synthesizing enzyme glutamic acid decarboxylase 65 (GAD65), and
      the receptor subunits GABA(Aalpha1) and GABA(B1) in the cerebellum of adult
      zebrafish. GABA and GAD65 presented a similar expression pattern that comprised
      the molecular layer, Purkinje cells and groups of presumed Golgi cells in the
      granular layer, both in the cerebellar corpus and valve. GABA(A) receptor
      subunits are principally found on fine radial fibers in the molecular layer,
      while GABA(B) receptor subunits localized prominently to the cell bodies of
      Purkinje cells in the ganglionic layer, and to their dendrites that span the
      molecular layer. These results are compared to the expression of the GABAergic
      system in the mammalian cerebellum.

PMID- 18633687
TI  - MR imaging-guided 10-gauge vacuum-assisted breast biopsy: histological
      characterisation.
AB  - PURPOSE: The aim of this study was to evaluate a handheld vacuum-assisted device
      for magnetic resonance imaging (MRI)-guided breast biopsy. MATERIALS AND METHODS:
      In 47 patients, a total of 47 suspicious breast lesions (mean maximum diameter 9
      mm) seen with MRI (no suspicious changes on breast ultrasound or mammography)
      were sampled using a 10-gauge vacuum-assisted breast biopsy (VAB) device under
      MRI guidance. Histology of biopsy specimens was compared with final histology
      after surgery or with follow-up in benign lesions. RESULTS: Technical success was
      achieved in all biopsies. Histological results from VAB revealed malignancy in 15
      lesions (32%), atypical ductal hyperplasia in four lesions (8%) and benign
      findings in 28 lesions (60%). One of four lesions with atypical ductal
      hyperplasia was upgraded to ductal carcinoma in situ after surgery. One of seven
      lesions showing ductal carcinoma was upgraded to invasive carcinoma after
      surgery. Two lesions diagnosed as infiltrating carcinoma by VAB were not
      validated at excisional biopsy due to complete removal of the lesion during the
      procedure. During the follow-up (mean 18 months) of histologically benign
      lesions, we observed no cases of breast cancer development. Because of
      morphological changes on follow-up MRI scans, two lesions underwent surgical
      excision, which confirmed their benign nature. Besides minor complications
      (massive bleeding, n = 1) requiring no further therapeutic intervention, no
      complications occurred. CONCLUSIONS: MRI-guided biopsy of breast lesions using a
      handheld vacuum-assisted device is a safe and effective method for the workup of
      suspicious lesions seen on breast MRI alone.

PMID- 18633688
TI  - Do diabetes and obesity promote hepatic fibrosis in familial heterozygous
      hypobetalipoproteinemia?

PMID- 18633689
TI  - Pulmonary hemorrhage, due to rupture of small muscular arteries, in an autopsy
      case of systemic lupus erythematosus with antiphospholipid antibodies.

PMID- 18633690
TI  - Anti-SS-A/Ro antibody determination by indirect immunofluorescence and comparison
      of different methods of anti-nuclear antibody screening: evaluation of the
      utility of HEp-2 cells transfected with the 60 kDa SS-A/Ro as a substrate.
AB  - We evaluated the utility of HEp-2 cells transfected with the 60 kDa SS-A/Ro as a
      substrate for indirect immunofluorescence (IIF-HEp-2000) to compare several
      methods for screening Japanese serum samples for anti-SS-A/Ro antibodies. Serum
      samples from 243 Japanese patients were analyzed by IIF for anti-nuclear
      antibodies (ANAs), using HEp-2 cells (IIF-HEp-2), and for anti-SS-A/Ro 60 kDa
      antibodies, using IIF-HEp-2000 and enzyme-linked immunosorbent assay (ELISA). We
      performed double immunodiffusion and immunoprecipitation experiments, using the
      products of in vitro transcription and translation, to analyze sera for which
      there were discrepancies in the results of the IIF-HEp-2000 assay and ELISA. A
      total of 93 of the 243 serum samples showed findings positive for anti-SS-A/Ro
      antibodies. Notably, eight of the 93 sera gave positive findings for anti-SS-A/Ro
      antibodies by IIF-HEp-2000 but ANA-negative by IIF-HEp-2 analysis. Seven sera
      possessing anti-SS-A/Ro antibodies gave false negative results by IIF-HEp-2000;
      however, those samples were all ANA positive. ELISA for anti-SS-A/Ro antibodies
      showed that five and two samples gave false positive and negative results,
      respectively. Analysis by IIF-HEp-2000 was useful for primary screening of
      patients for ANAs, especially for anti-SS-A/Ro antibodies; the test could detect
      anti-SS-A/Ro antibodies not identified on standard substrates in samples obtained
      from the Japanese population, as reported for the Caucasian population.

PMID- 18633691
TI  - Morphological, genetic, and chemical polymorphism of Curcuma kwangsiensis.
AB  - Previously, Chinese gajutsu available in Japan was identified, from the
      chloroplast trnK gene sequence, to be the rhizomes of Curcuma phaeocaulis and two
      genotypes of C. kwangsiensis. Although we defined the two genotypes, the pl and
      gl types, on the basis of the nucleotide difference, their external features did
      not correspond to the two phenotypes described in the literature. In this paper,
      to investigate the relationship between genotype and phenotype of C.
      kwangsiensis, a field investigation was carried out in its main cultivation areas
      of Guangxi Zhuangzu Autonomous Region and Guangdong Province, China, and sequence
      analysis of the trnK gene and single-nucleotide polymorphism (SNP) analysis of
      the nuclear 18S rRNA gene were performed on the collected specimens. Four
      genotypes of C. kwangsiensis were recognized from the combined 18S rRNA gene-trnK
      gene sequences: homozygote-K(gl)Wtk type, homozygote-K(pl)Ztk type, heterozygote
      K(gl)Wtk type, and heterozygote-Ltk type. Among the four genotypes, C.
      kwangsiensis in a field used for cultivation of gajutsu was of heterozygote
      K(gl)Wtk type. Formation of a heterozygote in the 18S rRNA gene might be a result
      of crossbreeding of C. kwangsiensis with several Curcuma species which had
      cytosine at nucleotide position 234. GC analysis of the rhizomes revealed that C.
      kwangsiensis was characterized by camphor and beta-elemene, and by detecting
      additional components such as curdione and curcumenol Curcuma species involved in
      the formation of the heterozygote might be speculated upon.

PMID- 18633692
TI  - Identification of major aroma compounds in the leaf of Morinda citrifolia Linn.
AB  - Morinda citrifolia, commonly named noni, has been used as food and as a folk
      medicine throughout the tropics. The use of the leaves to make hot water
      beverages is increasing in popularity, especially in Japan and the United States.
      To better understand the effects of processing on the content of the major aroma
      compounds, volatile oils were collected from samples of frozen, dried and roasted
      leaves by steam distillation and then analyzed by GC-MS. Drying of the leaves
      reduces the quantity of aroma compounds by more than half. Palmitic acid and E
      phytol were identified as the major components of the volatile oil. With the
      exception of E-phytol, all of the known volatile compounds identified in the leaf
      samples were done so for the first time.

PMID- 18633693
TI  - Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor
      bortezomib.
AB  - We present here a case of severe congestive cardiac failure, in a 47-year-old
      patient with myeloma who had no prior cardiac history, after receiving
      bortezomib. Bortezomib is a boron-containing molecule, which reversibly inhibits
      the proteasome, an intracellular organelle, which is central to the breakdown of
      ubiquitinated proteins and consequently crucial for normal cellular homeostasis.
      Phase II clinical trials demonstrate that it is effective for the treatment of
      relapsed refractory myeloma. Acute development of congestive cardiac failure
      associated with bortezomib therapy occurs very rarely or may be underestimated.
      Inhibition of proteasome activity may impair cardiac function due to accumulation
      of unfolded, damaged and undegraded proteins in myocytes. Patients with or
      without cardiac disease or previously received anthracycline-containing regimes
      should be closely monitored when being subjected to treatment with bortezomib.

PMID- 18633694
TI  - Pharmacological modulation of epithelial mesenchymal transition caused by
      angiotensin II. Role of ROCK and MAPK pathways.
AB  - PURPOSE: Tubulointerstitial fibrosis is a final common pathway to end-stage
      chronic kidney diseases, which are characterized by elevated renal angiotensin II
      (AngII) production. This peptide participates in kidney damage inducing fibrosis
      and epithelial mesenchymal transition (EMT). Our aim was to describe potential
      therapeutic targets in AngII-induced EMT, investigating the blockade of different
      intracellular pathways. METHODS: Studies were done in human tubular epithelial
      cells (HK2 cell line), evaluating changes in phenotype and EMT markers (Western
      blot and immunofluorescence). RESULTS: Treatment of HK2 cells with AngII for 3
      days caused transdifferentiation into myofibroblast-like cells. The blockade of
      MAPKs cascade, using specific inhibitors of p38 (SB203580), extracellular signal
      regulated kinase1/2 (ERK; PD98059) and Jun N-terminal kinase (JNK) (SP600125),
      diminished AngII-induced EMT. The blockade of RhoA/ROCK pathway, by transfection
      of a RhoA dominant-negative vector or by ROCK inhibition with Y-27632 or fasudil,
      inhibited EMT caused by AngII. Connective tissue growth factor (CTGF) is a
      downstream mediator of AngII-induced EMT. MAPKs and ROCK inhibitors blocked CTGF
      overexpression induced by AngII. HMG-CoA reductase inhibitors, although blocked
      AngII-mediated kinases activation, only partially diminished EMT and did not
      regulate CTGF. CONCLUSIONS: These data suggest a potential therapeutic use of
      kinase inhibitors in renal fibrosis.

PMID- 18633696
TI  - Medicalizing mental health: a phenomenological alternative.
AB  - With the increasingly close relationship between the pharmaceutical industry and
      the American Psychiatric Association (APA) there has been a growing tendency in
      the mental health professions to interpret everyday emotional suffering and
      behavior as a medical condition that can be treated with a particular drug. In
      this paper, I suggest that hermeneutic phenomenology is uniquely suited to
      challenge the core assumptions of medicalization by expanding psychiatry's narrow
      conception of the self as an enclosed, biological individual and recognizing the
      ways in which our experience of things--including mental illness--is shaped by
      the socio-historical situation in which we grow. Informed by hermeneutic
      phenomenology, psychiatry's first priority is to suspend the prejudices that come
      with being a medical doctor in order to hear what the patient is saying. To this
      end, psychiatry can begin to understand the patient not as a static, material
      body with a clearly defined brain dysfunction but as an unfolding, situated
      existence already involved in an irreducibly complex social world, an involvement
      that allows the patient to experience, feel, and make sense of their emotional
      suffering.

PMID- 18633695
TI  - Population PK-PD model for Fc-osteoprotegerin in healthy postmenopausal women.
AB  - Osteoporosis is a metabolic bone disease resulting from increased bone resorption
      and characterized by low bone mass that leads to increased bone fragility and
      risk of fracture, particularly of the hip, spine and wrist. Bone resorption is
      dependent on receptor activator of NF-kappa B ligand (RANKL), which binds to RANK
      receptor on preosteoclasts to initiate osteoclastogenesis and maintains
      osteoclast function and survival. To neutralize the effects of RANKL, the body
      naturally produces the protein osteoprotegerin (OPG), which acts as a decoy
      receptor for RANKL and contributes to bone homeostasis. We describe the piecewise
      development of a three-compartment pharmacokinetic model with both linear and
      Michaelis-Menten eliminations, and an indirect pharmacodynamic response model to
      describe the pharmacokinetics and pharmacodynamics, respectively, of the fusion
      protein, Fc-osteoprotegerin (Fc-OPG), in healthy postmenopausal women.
      Subsequently, model verification was performed and used to address study design
      questions via simulation. The model was developed using data from eight cohorts
      (n = 13 subjects/cohort; Fc-OPG:placebo = 10:3) classified by dose level (0.1,
      0.3, 1.0, or 3.0 mg/kg) and route of administration (intravenous [IV] or
      subcutaneous [SC]). Fc-OPG serum concentrations and urinary N
      telopeptide/creatinine ratios (NTX) following both IV and SC administration were
      available. The model provided an adequate fit to the observed data and
      physiologically plausible parameter estimates. Model robustness was tested via a
      posterior predictive check with the model performing well in most cases.
      Subsequent clinical trial simulations demonstrated that a single 3.0-mg/kg SC
      dose of Fc-OPG would be expected to produce, at 14 days post-dose, a median NTX
      percentage change from baseline of -45% (with a 95% prediction interval ranging
      from -34% to -60%). Lastly, model ruggedness was evaluated using local and global
      sensitivity analysis methods. In conclusion, the model selection and simulation
      strategies we applied were rigorous, useful, and easily generalizable.

PMID- 18633698
TI  - Complex questions asked by defense lawyers but not prosecutors predicts
      convictions in child abuse trials.
AB  - Attorneys' language has been found to influence the accuracy of a child's
      testimony, with defense attorneys asking more complex questions than the
      prosecution (Zajac & Hayne, J. Exp Psychol Appl 9:187-195, 2003; Zajac et al.
      Psychiatr Psychol Law, 10:199-209, 2003). These complex questions may be used as
      a strategy to influence the jury's perceived accuracy of child witnesses.
      However, we currently do not know whether the complexity of attorney's questions
      predict the trial outcome. The present study assesses whether the complexity of
      questions is related to the trial outcome in 46 child sexual abuse court
      transcripts using an automated linguistic analysis. Based on the complexity of
      defense attorney's questions, the trial verdict was accurately predicted 82.6% of
      the time. Contrary to our prediction, more complex questions asked by the defense
      were associated with convictions, not acquittals.

PMID- 18633697
TI  - Long-term immunological study in Graves' disease treated with thyroid arterial
      embolization.
AB  - OBJECTIVE: The aim of this study was to investigate long-term immunological
      changes after the treatment of Graves' disease (GD) with thyroid arterial
      embolization and the effect of thyroid arterial embolization on the body's
      immunological functions. MATERIALS AND METHODS: Forty-one patients with
      clinically and laboratorily ascertained GD were treated with thyroid arterial
      embolization and followed up for 3-54 months following embolization. Prior to
      embolization and at 1, 3, 6, 12, and 36 months following embolization, thyroid
      autoimmune antibodies were tested respectively, including thyroid stimulating
      antibody (TSAb), thyrotropin antibody (TRAb), thyroglobulin antibody (TGAb), and
      thyroid microsomal antibody (TMAb), as well as subgroup lymphocytes of
      CD16+CD56+, CD19+, CD3+, CD3+CD4+ and CD3+CD8+. The autoimmune status of GD
      patients prior to embolization and the dynamic changes of the immunological
      function after embolization were analyzed. RESULTS: The therapy of thyroid
      arterial embolization could effectively decrease the activity/titer and positive
      rate of TRAb and the ratio of CD4+/ CD8+ to normal levels at 6 months following
      embolization, while the ratio of CD3+CD8+ increased gradually to normal level at
      1 year following embolization. In patients with recurrence, TSAb and TRAb
      remained at a higher level, while the rate of CD3+CD8+ and the ratio of CD4+/CD8+
      were not statistically significantly different from those before embolization.
      CONCLUSION: Immunological functional disorder exists in GD patients. The
      treatment method of thyroid arterial embolization can effectively resume the
      basic immunological function to normal range while patients with recurrence have
      no significant improvement, suggesting that thyroid arterial embolization has an
      effective role in adjusting the immunological function.

PMID- 18633699
TI  - Reducing barriers to completing psychiatric advance directives.
AB  - OBJECTIVE: Psychiatric advance directives (PADs) allow individuals to plan for
      future mental health treatment. However, little is known about barriers to PAD
      completion. This paper examines an intervention's effect in reducing barriers to
      PAD completion. METHOD: Patients were randomly assigned to a facilitated PAD
      session or control group. Barriers associated with (1) the PAD documents and (2)
      external support for PADs were assessed at baseline (n = 462), 6 months (n = 380)
      and 1 year (n = 362). RESULTS: There were no significant baseline between-group
      differences on the two barriers. However, at follow-up both barriers were
      significantly lower in the experimental group. Further, barriers were predictive
      of PAD completion. CONCLUSIONS: Structured facilitation can significantly reduce
      barriers to PAD completion. However, the intervention did not eliminate barriers.
      Findings are discussed in the context of possible system-level changes to further
      reduce barriers to PAD completion.

PMID- 18633700
TI  - Caution should be taken in the methodology used to confirm c.156_157insAlu BRCA2
      mutation.

PMID- 18633701
TI  - Survey of O-GlcNAc level variations in Xenopus laevis from oogenesis to early
      development.
AB  - Little is known about the impact of O-linked-N-acetylglucosaminylation (O-GlcNAc)
      in gametes production and developmental processes. Here we investigated changes
      in O-GlcNAc, UDP-GlcNAc and O-GlcNAc transferase (OGT) levels in Xenopus laevis
      from oogenesis to embryo hatching. We showed that in comparison to stage VI,
      stages I-V oocytes expressed higher levels of O-GlcNAc correlating changes in OGT
      expression, but not in UDP-GlcNAc pools. Upon progesterone stimulation, an O
      GlcNAc level burst occurred during meiotic resumption long before MPF and Mos
      Erk2 pathways activations. Finally, we observed high levels of O-GlcNAc, UDP
      GlcNAc and OGT during segmentation that decreased concomitantly at the onset of
      gastrulation. Nevertheless, no correlation between the glycosylation, the
      nucleotide-sugar and the glycosyltransferase was observed after neurulation. Our
      results show that O-GlcNAc is regulated throughout oogenesis and development
      within a complex pattern and suggest that dysfunctions in the dynamics of this
      glycosylation could lead to developmental abnormalities.

PMID- 18633702
TI  - Does hypothermic treatment provide an advantage after spinal cord injury until
      surgery? An experimental study.
AB  - We compared the effects of early and late stage hypothermia treatment after
      spinal cord injury. Five groups each consisting of seven rats were included in
      this study. In Group 1a (Clip applied-non-treatment group) and Group 1b (Clip
      applied-treated group) the spinal cords were harvested 1 h after the injury. In
      Group 2a (clip applied, non-treated group) and Group 2b (clip applied-treated
      group) the injured segments were harvested 24 h after injury. Group 3 was
      designed as the sham-operated group. The significantly lower levels of TBARS and
      GSH-Px in Group 2a, as compared with Group 1b suggests that the hypothermia was
      effective in the early stage of treatment (P < 0.05). In contrast, TBARS and GSH
      Px levels were significantly increased at the 24 h timepoint following treatment
      (P < 0.05). Short-term systemic hypothermia reduces lipid peroxidation in the
      early stages after spinal cord injury. This beneficial effect disappears 24 h
      following systemic hypothermic treatment.

PMID- 18633703
TI  - Electroacupuncture reduces voluntary alcohol intake in alcohol-preferring rats
      via an opiate-sensitive mechanism.
AB  - Electroacupuncture (EA) has been shown to modify the effects of various drugs of
      abuse, including alcohol. Inbred P rats were trained to drink alcohol voluntarily
      and then subjected to two periods of alcohol deprivation lasting 3 days. During
      the second deprivation, the rats received either EA or sham EA. The rats were
      pretreated with naltrexone (5 mg/kg) or saline 30 min before each of the EA or
      sham EA sessions. Approximately 6 h after the last naltrexone or saline
      treatment, the alcohol tubes were returned and alcohol and water intakes were
      recorded later at 2, 4, 6, and 24 h. Only EA led to a decrease in alcohol intake,
      which was most prominent at 6 and 24 h, and this inhibitory effect of EA was
      blocked by naltrexone, suggesting that activation of the endogenous opiate system
      may be responsible for EA's effects on alcohol intake in the alcohol-dependent iP
      rats.

PMID- 18633704
TI  - Needs and preferences for receiving mental health information in an African
      American focus group sample.
AB  - The purpose of this study is to better understand the mental health/illness
      information and service delivery preferences among African American residents of
      Baltimore. We conducted four focus groups (n = 42) among African American adults
      currently unconnected with the mental health system. Participants expressed fear
      of stigma and perceptions of racism as major barriers to seeking information
      and/or services and discussed some normalizing strategies to address these
      barriers. African Americans harbor cultural and traditional beliefs regarding
      mental illness which could also act as barriers. Findings have implications for
      imparting acceptable and culturally sensitive mental health education and service
      delivery programs in community settings.

PMID- 18633705
TI  - Prospective study of psychiatric follow-up default and medication compliance
      after discharge at a psychiatric hospital in Nigeria.
AB  - We report a prospective follow-up of 81 patients recently discharged from the
      hospital. Their hospital attendance pattern, medication compliance, mental state
      and social functioning were measured. Defaulters were followed up in the
      community. At 3 months, 49.4% had defaulted, while 51.5% were medication
      noncompliant. Clinical outcome was best for the Non-Defaulter-Medication
      Compliant (ND-MC) group, worst for the Defaulter-Medication Non-Compliant (D-MNC)
      group. Reasons for default include feeling well, financial difficulty, medication
      side effects and stigma. Medication non-compliant patients were more likely to
      reside more than 20 km away from hospital. There is an urgent need to provide
      community psychiatric services to improve patients' access to services and
      medication compliance.

PMID- 18633706
TI  - Body mass index and gastroesophageal reflux disease: implications of the obesity
      epidemic.

PMID- 18633707
TI  - Increased folate intake with no changes in serum homocysteine and decreased
      levels of C-reactive protein in patients with inflammatory bowel diseases.
AB  - In order to increase dietary folic acid intake and to improve nutritional status
      regarding folate by controlling homocysteine concentrations, ten patients with
      inflammatory bowel diseases (Crohn's disease in the colon and ulcerative colitis)
      received individualized nutritional guidance and were followed up as outpatients
      for 2 months. The following procedures were performed at the beginning of the
      study (T0), after 1 month (T1) and at the end of the study (T2): collection of
      anthropometric data (weight and height), dietary data (24 h diet recall), and
      blood under fasting condition for the determination of serum folic acid,
      homocysteine, C-reactive protein, and vitamin B12. Plasma folic acid deficiency
      was not detected but hyperhomocysteinemia was present in six individuals and C
      reactive protein (CRP) was increased (>0.5 mg/dl) in seven patients. After the
      patients were instructed there was a significant increase in vitamin B6 intake
      (about 35%) and in folate intake (49.6%). Mean plasma levels of folic acid,
      homocysteine, and vitamin B12 did not change, but there was a significant
      decrease of CRP at T1, 0.36 mg dl(-1) on average (P = 0.01), which was maintained
      at T2. We conclude that the increased folate intake reported by this group of
      patients was not reflected in improved serum concentrations of folic acid and
      homocysteine. However, the guidelines for the patients probably induced them to
      choose a more adequate diet, providing nutrients that help control the
      inflammatory process.

PMID- 18633709
TI  - Perceived harmfulness predicts nonmedical use of prescription drugs among college
      students: interactions with sensation-seeking.
AB  - This study describes the level of perceived harmfulness of nonmedical
      prescription stimulant and analgesic use in a sample of college students, and
      examines the prospective relationship between perceived harmfulness and
      subsequent nonmedical use. In addition, we explore whether the association
      between perceived harmfulness and nonmedical use varies by level of sensation
      seeking. Personal interviews, including questions on sensation-seeking and drug
      use, were conducted with 1,253 first-year college students. Participants were
      then followed-up twice at 6-month intervals. Perceived harmfulness of nonmedical
      use of prescription drugs was assessed at 6 months via a web-based survey. At the
      12-month follow-up interview, drug use was again assessed. Students who never had
      the opportunity to use prescription drugs nonmedically were excluded from all
      analyses. Results revealed that one in four students perceived a great risk of
      harm from occasional nonmedical use of prescription stimulants (25.2%) and
      analgesics (27.8%). As expected, low perceived harmfulness and high sensation
      seeking were independently associated with increased risk of nonmedical use,
      holding constant demographic characteristics. The protective effect of high
      perceived harmfulness could be seen at all levels of sensation-seeking with one
      important exception: Among high sensation-seekers, perceived harmfulness was not
      related to nonmedical use of prescription analgesics. Perceived harmfulness
      appears to distinguish nonmedical users from non-users, given the opportunity to
      use. Increasing perceived harmfulness may be a viable prevention strategy for
      most students, but alternative approaches might need to be developed that are
      tailored to high sensation-seekers.

PMID- 18633708
TI  - Estimation of the potential antitumor activity of microencapsulated Lactobacillus
      acidophilus yogurt formulation in the attenuation of tumorigenesis in Apc(Min/+)
      mice.
AB  - There is a strong correlation between orally administered probiotics and
      suppression of the low-grade inflammation that can lead to restoration of normal
      local immune functions. We studied the potential immunomodulatory and
      antitumorigenic properties of microencapsulated probiotic bacterial cells in a
      yogurt formulation in Min mice carrying a germline APC mutation. Daily oral
      administration of microencapsulated Lactobacillus acidophilus bacterial cells in
      the yogurt formulation mice resulted in significant suppression of colon tumor
      incidence, tumor multiplicity, and reduced tumor size. Results show that oral
      administration of microencapsulated L. acidophilus contributed to the
      stabilization of animal body weight and decreased the release of bile acids.
      Histopathological analyses revealed fewer adenomas in treated versus untreated
      animals. Furthermore, treated animals exhibited fewer gastrointestinal intra
      epithelial neoplasias with a lower grade of dysplasia in detected tumors. Results
      suggest that oral administration of microencapsulated probiotic L. acidophilus
      exerts anti-tumorous activity, which consequently leads to reduced tumor outcome.

PMID- 18633710
TI  - Implementation science: promoting science-based approaches to prevent teen
      pregnancy.
AB  - This paper reports the results of a project funded by the Centers for Disease
      Control and Prevention intended to promote the use of science-based approaches to
      teen pregnancy prevention. As with other efforts to promote diffusion of
      innovations, adoption of these successful programs faced a number of barriers
      including lack of knowledge of programs that work, lack of funding for training
      and materials, devaluing science-based approaches, complexity of successful
      programs, politics, funding streams and compatibility with particular community
      characteristics. Nevertheless, five state and three national teen pregnancy
      organizations provided intensive technical assistance, produced materials, and
      provided training to encourage use of programs that work. Local barriers to their
      work included the fact that teen pregnancy rates were already dropping,
      instability of funding to pay for such programs, turnover of agency staff, the
      need for intensive follow-up to promote adoption, the internal organization of
      the initiative, and the fragility of local teen pregnancy prevention coalitions.
      Still, in each of five states, there was increased adoption of science-based
      approaches to prevent teen pregnancy.

PMID- 18633711
TI  - Anisotropic nature of mouse lung parenchyma.
AB  - Lung parenchyma is normally considered to be isotropic, that is, its properties
      do not depend upon specific preferential directions. The assumption of isotropy
      is important for both modeling of lung mechanical properties and quantitative
      histologic measurements. This assumption, however, has not been previously
      examined at the microscopic level, in part because of the difficulty in large
      lungs of obtaining sufficient numbers of small samples of tissue while
      maintaining the spatial orientation. In the mouse, however, this difficulty is
      minimized. We evaluated the parenchymal isotropy in mouse lungs by quantifying
      the mean airspace chord lengths (Lm) from high-resolution histology of complete
      sections surrounded by an intact continuous visceral pleural membrane. We
      partitioned this lung into 5 isolated regions, defined by the distance from the
      visceral pleura. To further evaluate the isotropy, we also measured Lm in two
      orthogonal spatial directions with respect to the section orientation, and varied
      the sample line spacing from 3 to 280 microm. Results show a striking degree of
      parenchymal anisotropy in normal mouse lungs. The Lm was significantly greater
      when grid lines were parallel to the ventral-dorsal axis of the tissue. In
      addition the Lm was significantly smaller within 300 microm of the visceral
      pleura. Whether this anisotropy results from intrinsic structural factors or from
      nonuniform shrinkage during conventional tissue processing is uncertain, but it
      should be considered when interpreting quantitative morphometric measurements
      made in the mouse lung.

PMID- 18633712
TI  - Disorders of sex development (DSDs), their presentation and management in
      different cultures.
AB  - The way disorders of sex development (DSD) are viewed and managed in different
      cultures varies widely. They are complex conditions and even well-educated lay
      people find them difficult to understand, but when families are very poor and
      lacking in basic education, and the health system is starved of resources,
      traditional beliefs, folk remedies and prejudice combine to make the lives of
      children and adults with DSD extremely difficult and sad. Rumour and
      discrimination isolate them from their communities and they become devalued.
      People with DSDs desire the same things in life as everyone else-to find someone
      who will love them, to be valued as human beings, to feel at home in their own
      bodies, to be able to have satisfactory sexual relations should these be desired,
      to be able to trust their medical advisers and to be integrated into the general
      community. Long term outcome studies have been published from many countries, but
      these studies have not necessarily been critical of the values that underpinned
      the type of treatment given to the patients. There is a need for standardized
      instruments that would allow a true comparison of the quality of outcomes from
      the patients' perspective. Much could be done to improve equity between rich and
      poor countries for the benefit of people with DSDs. A focus on developing cheap,
      robust diagnostic tests, making essential medicines available for all, training
      surgeons to do better operations, educating health professionals, families and
      the general community in order to break down prejudice against people with DSDs,
      and training mental health workers in this specialized field, would do much to
      alleviate the burden of the condition.

PMID- 18633713
TI  - Early stages for Parkinson's development: alpha-synuclein misfolding and
      aggregation.
AB  - Misfolding and aggregation of proteins are common threads linking a number of
      important human health problems, including various neurodegenerative disorders
      such as Parkinson's disease in particular. The first and perhaps most important
      elements in most neurodegenerative processes are misfolding and aggregation of
      specific proteins. Despite the crucial importance of protein misfolding and
      abnormal interactions, very little is currently known about the molecular
      mechanism underlying these processes. Factors that lead to protein misfolding and
      aggregation in vitro are poorly understood, in addition to the complexities
      involved in the formation of protein nanoparticles with different morphologies
      (e.g. nanopores and other species) in vivo. A clear understanding of the
      molecular mechanisms of misfolding and aggregation will facilitate rational
      approaches to prevent protein misfolding mediated pathologies. To accomplish this
      goal and to elucidate the mechanism of protein misfolding, we developed a novel
      nanotechnology tool capable of detecting protein misfolding. We applied single
      molecule probing technique to characterize misfolding and self-assembly of alpha
      synuclein dimers, which is the very first step of the aggregation process. Using
      AFM force spectroscopy approach, we were able to detect protein misfolding via
      enhanced interprotein interaction. Moreover, such an important characteristic as
      the lifetime of dimers formed by misfolded alpha-synuclein was measured. These
      data suggest that compared to highly dynamic monomeric forms, alpha-synuclein
      dimers are practically static and thus can play a role of aggregation nuclei for
      the formation of aggregates. Importantly, two different dissociation channels
      were detected suggesting that aggregation process can follow different pathways.
      The application of these findings for understanding of the aggregation phenomenon
      and the development of the disease is discussed.

PMID- 18633714
TI  - Specificity and accuracy data for ligand-binding assays for macromolecules should
      be interpreted with caution.

PMID- 18633715
TI  - Identification of C-terminal neighbours of amino acid residues without an
      aliphatic 13Cgamma as an aid to NMR assignments in proteins.
AB  - We propose a methodology that uses GFT (3,2)D CB(CACO)NNH experiment to rapidly
      collect the data and readily identify six amino acid residue types (Ala, Asn,
      Asp, Cys, Gly and Ser) in any given protein. Further, the experiment can
      distinguish the redox state of Cys residues. The proposed experiment in its two
      forms will have wide range of applications in resonance assignment strategies and
      structure determination of proteins.

PMID- 18633716
TI  - Including organizational ethics in policy review processes in healthcare
      institutions: a view from Canada.

PMID- 18633717
TI  - Amylase gene silencing by RNA interference improves recombinant hGM-CSF
      production in rice suspension culture.
AB  - A rice cell suspension culture system with the Ramy3D promoter, which is induced
      by sucrose starvation, has been previously utilized to produce large quantities
      of recombinant proteins. Although this expression system was reported previously
      to generate a good yield of recombinant hGM-CSF in transgenic rice cell
      suspension culture, rice alpha-amylase was a dominant protein, with 43% of total
      secreted proteins and an obstacle to the production and purification of secreted
      recombinant proteins in a rice cell suspension culture. In this study, an intron
      containing self-complementary hairpin RNA (ihpRNA)-mediated post transcriptional
      gene silencing (PTGS) strategy for the rice alpha-amylase gene was applied in
      order to overcome this problem in rice cell suspension culture systems. The
      reduction of the mRNA level of the rice alpha-amylase gene was verified via
      Northern blot analysis and siRNA, an initiator of RNA interference, was detected
      via an RNase protection assay. The amount of rice alpha-amylase in the culture
      medium was reduced to 8.2% as compared to that of the wild-type. A transgenic
      rice cell suspension culture expressing both the hGM-CSF and ihpRNA of the rice
      alpha-amylase gene demonstrated that the quantity of rice alpha-amylase was
      reduced to 22% and that the accumulation of hGM-CSF increased by 1.9-fold as
      compared to that in the transgenic cell line expressing hGM-CSF only. These
      results indicated that RNAi technology should be of great utility for suppressing
      undesirable genes, and should improve accumulation and facilitate the
      purification of secreted recombinant proteins in rice cell suspension cultures.

PMID- 18633718
TI  - Biodegradation kinetics of trans-4-methyl-1-cyclohexane carboxylic acid.
AB  - Naphthenic acids are a complex mixture of organic compounds which naturally occur
      in crude oil. Low molecular weight components of the naphthenic acids are known
      to be toxic in aquatic environments and there is a need to better understand the
      factors controlling the kinetics of their biodegradation. In this study, a
      relatively low molecular weight naphthenic acid compound (trans-isomer of 4
      methyl-1-cyclohexane carboxylic acid) and a microbial culture developed in our
      laboratory were used to study the biodegradation of this naphthenic acid and to
      evaluate the kinetics of the process in batch cultures. The initial concentration
      of trans-4-methyl-1-cyclohexane carboxylic acid (50-750 mg l(-1)) did not affect
      the maximum specific growth rate of the bacteria at 23 degrees C (0.52 day(-1))
      to the maximum biodegradable concentration (750 mg l(-1)). The maximum yield
      observed at this temperature and at a neutral pH was 0.21 mg of biomass per
      milligram of substrate. Batch experiments indicated that biodegradation can be
      achieved at low temperatures; however, the biodegradation rate at room
      temperature (23 degrees C) and neutral pH was 5 times faster than that observed
      at 4 degrees C. Biodegradation at various pH conditions indicated a maximum
      specific growth rate of 1.69 day(-1) and yield (0.41 mg mg(-1)) at a pH of 10.

PMID- 18633719
TI  - A synthesis of variability in nearshore Alaskan marine populations.
AB  - One of the primary goals of any monitoring program is to detect anthropogenic
      changes; however natural variability can be so high that it prevents detection of
      human-induced effects. This project synthesized existing data to identify
      patterns of temporal variation within nearshore marine habitats in the Gulf of
      Alaska and was motivated by the need for monitoring in this environment
      vulnerable to oil spills, such as the Exxon Valdez. I collected 786 time series
      that were greater than 2 years in length from unimpacted (control) sites for 226
      species. Temporal variability (CV) varied widely from 1% to 447%, averaged 89%,
      and was not significantly different among marine populations of birds, mammals,
      fish, algae and invertebrates. Temporal variability of invertebrates and algae
      were not significantly different when abundance was measured as biomass, percent
      cover or density. Both invertebrates and algae showed higher variability in low
      intertidal habitat compared to high intertidal habitat. For invertebrates,
      populations on bedrock substrates had greater temporal variability than those on
      cobble or soft sediment substrates, while there was not a significant difference
      for algae on either cobble or bedrock substrates. Many of these results are
      surprising, given differences in movement patterns, survey methods, life
      histories, and so forth. These results suggest that no single group, measure or
      habitat will be better or worse for monitoring and detecting change.
      Understanding variability is a difficult task, but until we tackle it, we will
      likely not understand or have predictive capabilities in ecological populations
      and communities.

PMID- 18633720
TI  - Ecotoxicological sediment evaluations in marine aquaculture areas of Chile.
AB  - Given its geographic characteristics, the southern Chilean fjord area is
      subjected to growing environmental pressure from the development of diverse forms
      of aquaculture (i.e., fish, algae, shellfish). The sediments accumulate
      substances as a natural sink, and ecotoxicology assays offer a reliable and
      robust proxy for sediment quality analyses. This study's objective was to
      establish a mid-range toxicity base line for the sediments in the region by
      applying a battery of non-specific ecotoxicological assays. Sediment samples (28)
      were collected in the channels and fjords studied during the CIMAR-Fiordos 11
      cruise (July 2005). The sediments were evaluated using different species endemic
      to the eastern Pacific as targets: Ampelisca araucana, Tisbe longicornis, Arbacia
      spatuligera, and Dunaliella tertiolecta. The conditions for each assay were
      reported previously. Of the four species used as ecotoxicological tools, only D.
      tertiolecta differed significantly from the control group (negative) in terms of
      its growth. This difference could be attributed to nutrient enrichment. In
      general, we concluded that, although local changes occurred in the sediments, the
      mesoscale magnitude of the ecotoxicological alterations was small. Nonetheless, a
      surveillance program should be implemented that would allow us to follow-up and
      analyze the changes that are taking place in the systems on broader scales of
      time and space.

PMID- 18633721
TI  - Ambiental dust speciation and metal content variation in TSP, PM 10 and PM 2.5 in
      urban atmospheric air of Harare (Zimbabwe).
AB  - Levels of TSP, PM(10) and PM(2.5) as well as levels of Pb, Co, Ni and Cd in TSP,
      PM(10) and PM(2.5) have been determined in atmospheric particulates collected at
      Loius Mountbatten School (Harare). The samples were collected for a period of 6
      months from July to December 2002. The average levels of TSP, PM(10) and PM(2.5)
      measured at the site are 106.11, 59.70 and 40.55 mg m(-3) respectively. The
      average level of TSP at Loius Mountbatten School is 106.11 mg m(-3), which is
      higher than the annual WHO guideline limit of 90 mg m(-3). The average level of
      PM(10) measured at Loius Mountbatten School is 59.70 mg m(-3), and is higher than
      the US-EPA and UK-EU guideline limit of 50 mg m(-3). The average level of PM(2.5)
      measured at the site are also higher than the WHO and US-EPA annual guideline
      limit of 15 mg m(-3). The analysis of metal concentrations in TSP, PM(10) and
      PM(2.5) was done using Graphite Furnace Atomic Absorption Spectrometry (GFAAS).
      The analysis showed the following average elemental concentrations: 0.157 mg Pb
      m(-3) in TSP, 0.166 mg Pb m(-3) in PM(10), 0.185 mg Pb m(-3) in PM(2.5), 0.009 mg
      Co m(-3) in TSP, 0.007 mg Co m(-3) in PM(10), 0.011 mg Co m(-3) in PM(2.5), 0.223
      mg Ni m(-3) in TSP, 0.166 mg Ni m(-3) in PM(10), 0.180 mg Ni m(-3) in PM(2.5) and
      0.005 mg Cd m(-3) in TSP, 0.006 mg Cd m(-3) in PM(10), 0.005 mg Cd m(-3) in
      PM(2.5). The levels of Pb and Ni were generally higher than those of Co and Cd
      and this could have been due to high traffic volumes and various industrial
      activities in the Workington Industrial Area.

PMID- 18633722
TI  - Abundance of sewage-pollution indicator and human pathogenic bacteria in a
      tropical estuarine complex.
AB  - Studies on abundance and types of various pollution indicator bacterial
      populations from tropical estuaries are rare. This study was aimed to estimate
      current levels of pollution indicator as well as many groups of human pathogenic
      bacteria and their seasonal variations in different locations in Mandovi and
      Zuari Rivers in the central west coast of India. The sampling covered the
      estuarine and upstream regions of these rivers representing premonsoon (May
      2005), monsoon (September 2006) and post-monsoon (November 2005). Both the
      abundance and types of autochthonous and allochthonous microbial populations in
      the near shore environments are affected by land drainages, domestic sewage
      outfalls and other discharges. The overall ranges (and their mean abundance; no.
      ml(-1)) of the monitored groups of bacteria were: total coliforms: 0-29,047
      (3,134 ml(-1)); total streptococci: 3-14,597 (798); total vibrios: 13-42,275
      (2,530); Escherichia coli: 0-1,333 (123); Vibrio cholerae: 0-3,012 (207);
      Salmonella spp: 0-1,646 (90); Streptococcus faecalis: 0-613 (88) and Aeromonas
      spp: 0-2,760 (205). In general, abundance of sewage pollution indicator bacteria
      such as total coliforms and total streptococci was lower than that reported from
      many other locations worldwide.

PMID- 18633723
TI  - Development of rapid bioassessment approaches using benthic macroinvertebrates
      for Thai streams.
AB  - Thailand currently lacks formal bioassessment approaches and protocols to assist
      management decisions for water quality. The aim of this research is to develop a
      practical method of rapid bioassessment for a professional level by using benthic
      macroinvertebrate assemblages for streams in Thailand. Eleven reference and nine
      test sites were sampled in the headwater streams of the Loei River and adjacent
      areas to explore the development of a practical protocol. Specific physico
      chemical parameters were selected to provide ecological information supplemental
      to the biological indicators. The biological research was designed around the
      USEPA Rapid Bioassessment Protocols (RBPs) using the multi-habitat approach. Four
      fixed-count subsamplings (100, 200, 300 and 500 organisms) were randomly
      conducted using a standardized gridded pan to evaluate an appropriate level for
      bioassessment in Thai streams. A 300 organism subsample is adequate for
      bioassessment purposes in Thai stream (evaluated by calculating dissimilarity
      values and ordination techniques). A systematic selection of candidate reference
      sites, metric selection, and index calibration was part of this research.
      Multimetric and multivariate analyses were examined as a foundation for
      bioassessment in Thailand. The multimetric approach appears to be more practical
      for a rapid bioassessment technique. Nine core metrics were identified for
      biological index score including number of total taxa, Diptera taxa,
      Ephemeroptera, Plecoptera, Trichoptera, and Coleoptera taxa, (%) Plecoptera, (%)
      Tolerant organisms, Beck's Biotic Index, (%) Intolerant organisms, Shredders taxa
      and Clingers taxa were calibrated for the final index. As a result of multimetric
      and multivariate analyses, family level identification data effectively
      discriminated reference condition and broad-scale environmental gradients.
      Hampered by incomplete taxonomic knowledge of benthic macroinvertebrates in
      Thailand, family-level identification may be sufficient taxonomic resolution for
      rapid bioassessment in Thailand.

PMID- 18633724
TI  - Sea water intrusion studies near Kovaya limestone mine, Saurashtra coast, India.
AB  - The Kovaya Limestone Mine is situated on the Saurashtra coast of India. Though
      the mine is dependent on the desalination plant installed in the plant for its
      domestic and industrial water requirements, there is significant withdrawal of
      groundwater by the large number of bore wells and open wells, which are present
      in the agricultural fields lying in and around the leased area of the mine. The
      heavy withdrawal of groundwater has led to intrusion of seawater. The present
      work entails study of possible seawater intrusion by chemical analysis of major
      cations and anions in selected groundwater samples. Very high total dissolved
      solids in the range of >1,000 mg/l and high chloride in the range of 103 mg/l to
      3,899 mg/l have been measured in the groundwater samples. 'Resistivity Imaging
      Survey' has also been carried out on selected profiles in the study area. The
      Electrical Resistivity Tomography images indicate very low resistivity zones (~0
      3 Omega m) in the bottom portion of the resistivity depth section. These low
      resistivity zones can be interpreted to be due to seawater intrusion. The
      resistivity sections on the excavated Pits, where mining is going on, indicate
      possibilities of seawater intrusion. Hence, protection from seawater intrusion is
      recommended through restriction of mining up to the safe level.

PMID- 18633725
TI  - Development of a method to investigate medical students' perceptions of their
      personal and professional development.
AB  - Personal and Professional Development (PPD) is now key to the undergraduate
      medical curriculum and requires provision of appropriate learning experiences. In
      order to achieve this, it is essential that we ascertain students' perceptions of
      what is important in their PPD. We required a methodological approach suitable
      for a large medical school, which defines constructs used by the students to
      describe their PPD, and is not constrained by a researcher's predetermined line
      of questioning. It should also quantify the saliencies of these constructs in the
      student population and indicate how they gauge their own PPD. The instrument
      should also be suitable for administration at key stages of the students'
      learning experience. Here we describe the first stages in developing a novel
      method, which fulfils these requirements. It is based on a modified self
      repertory grid, the "Ideal Self" Inventory. All first year students (N = 379),
      provided five descriptors of a "good medical student" and of a not very good
      medical student, which generated 1,531 'ideal' qualities. To define underlying
      themed constructs, 49 randomly selected descriptors, were grouped together by
      self selected students (n = 55), using commonly held assumptions. Frequency of
      item co-occurrence was tabulated by multidimensional scaling. Themed clusters of
      'ideal' qualities, defined by hierarchical cluster analysis, were overlaid onto
      the multidimensional scaling to generate a concept map. This revealed seven
      themed constructs; Personal Welfare, Time and Self Management Committed Work
      Ethic, Learning Skills, Personal Development/Reflection, Personal and
      Professional Conduct and Teamwork. We then analysed the 1,531 'ideal' qualities,
      by determining the frequency with which students used each construct and the
      proportion of students who used a construct at least once. Personal and
      Professional Conduct, Committed Work Ethic and Time and Self Management were the
      most frequently used, implying that they were the most salient for the first year
      students.

PMID- 18633726
TI  - Health-related quality of life after hand-assisted laparoscopic and open radical
      nephrectomies of renal cell carcinoma.
AB  - AIM: To compare the health-related quality of life (HRQOL) in contemporaneous
      groups of patients undergoing hand-assisted laparoscopic radical nephrectomy
      (HALRN) or open radical nephrectomy (ORN) for renal cell carcinoma (RCC).
      PATIENTS AND METHODS: The clinical data of 20 cases receiving hand-assisted
      laparoscopic radical nephrectomy (the HALRN group) and 51 cases receiving open
      radical nephrectomy (the ORN group) were analyzed retrospectively and health
      questionnaires were mailed to these patients at 1 year postoperatively. The two
      groups were compared in terms of general surgery-related information, tumor
      characteristics, days to return to work or routine daily activities, and health
      related quality-of-life scales. RESULTS: Patients in the HALRN group had
      significantly less mean incision length (6.25 versus 17.8 cm), faster return to
      work or routine daily activities (5.3 versus 8.6 weeks), and earlier out-of-bed
      activity (4.76 versus 6.59 days) compared with those in the ORN group (P < 0.05).
      There were no significant differences in HRQOL scales at 1 year between the both
      groups (P > 0.05). CONCLUSION: The results showed that hand-assisted laparoscopic
      surgery is a minimally invasive surgical technique for RCC offering earlier
      recovery and similar long-term HRQOL compared with open surgery.

PMID- 18633727
TI  - Relation between three-dimensional echocardiography derived left ventricular
      volume and MRI derived circumferential strain in patients eligible for cardiac
      resynchronization therapy.
AB  - OBJECTIVES: To compare regional left ventricular (LV) volume curves obtained with
      real time three-dimensional echocardiography (RT3DE) with two-dimensional
      circumferential strain curves obtained by MRI in cardiac resynchronization
      therapy candidates. BACKGROUND: Several methods using either ultrasound or MRI
      are used to quantify mechanical dyssynchrony (MD). Theoretically, LV volume and
      circumferential strain seem related, since both measures are connected to the
      radius of the ventricle. METHODS: In 21 patients with chronic heart failure,
      RT3DE and tagged MRI were performed subsequently. Regional LV volume was computed
      from the ultrasound images. From the MR images, regional circumferential strain
      was calculated. Cross-correlations with time lags of 1% of the cardiac cycle were
      performed to compare the curves in corresponding LV segments. Furthermore, peak
      septal to lateral (SL) delays were compared between modalities. RESULTS: High
      correlations were found between the curves (r(2) = 0.65 +/- 0.19), but regional
      differences in time delay between modalities were observed. In the septum, the
      volume curve was earlier than the strain curve by 1.8 +/- 17.0 time-lags (n.s.),
      while in the lateral wall, the volume curve was earlier by 3.3 +/- 12.0 time-lags
      (P < 0.02). There was a non-significant difference between SL delays in the two
      modalities (volume: -1.0 +/- 8.6%, strain: 3.0 +/- 12.7%, P = 0.17, a positive
      sign indicates that the lateral wall is delayed). CONCLUSIONS: High correlations
      were observed between both modalities, but regional differences in time-delay
      were found. This is possibly inherent to the method of echocardiographic volume
      calculation and hampers the comparison of both measures for the quantification of
      MD.

PMID- 18633728
TI  - Institutional mistrust in the organization of pharmaceutical clinical trials.
AB  - In this paper I explore the politics of trust in the clinical testing of
      pharmaceuticals in the US. Specifically, I analyze trust in terms of its
      institutional manifestations in the pharmaceutical clinical trials industry. In
      the process of testing new drugs, pharmaceutical companies must (1) protect their
      proprietary information from the clinicians who conduct their studies, and (2)
      find a way to ensure human subjects' compliance to study protocols. Concern with
      these two critical issues leads drug companies to approach clinicians and
      research subjects with an attitude of mistrust and the desire to exert control
      over their activities. This orientation results in an institutionalization of
      mistrust that structures the relationships and activities required for the
      clinical development of new pharmaceutical products.

PMID- 18633729
TI  - Regulation and the social licence for medical research.
AB  - Regulation and governance of medical research is frequently criticised by
      researchers. In this paper, we draw on Everett Hughes' concepts of professional
      licence and professional mandate, and on contemporary sociological theory on risk
      regulation, to explain the emergence of research governance and the kinds of
      criticism it receives. We offer explanations for researcher criticism of the
      rules and practices of research governance, suggesting that these are perceived
      as interference in their mandate. We argue that, in spite of their complaints,
      researchers benefit from the institutions of governance and regulation, in
      particular by the ways in which regulation secures the social licence for
      research. While it is difficult to answer questions such as: "Is medical research
      over-regulated?" and "Does the regulation of medical research successfully
      protect patients or promote ethical conduct?", a close analysis of the social
      functions of research governance and its relationship to risk, trust, and
      confidence permits us to pose these questions in a more illuminating way.

PMID- 18633730
TI  - Exploring response shift in the quality of life of healthy adolescents over 1
      year.
AB  - BACKGROUND: The assessment of child and adolescent quality of life (QoL) is
      increasingly incorporated into practice and research within health and social
      care. However, little is known about the stability of the conceptualisation of
      QoL in the face of normative developmental processes against which to compare
      changes in response to non-normative events, such as chronic illness. The present
      study examined the stability of the QoL construct over 1 year in a cohort of
      healthy community-dwelling adolescents through applying the response shift (RS)
      model. METHOD: A cohort of 356 adolescents (M age = 14.05 years) completed the
      Kidscreen QoL measure on two occasions, 1 year apart. Both research-design and
      statistical techniques were employed to assess three types of RS: recalibration,
      reprioritisation and reconceptualisation. RESULTS: A significant recalibration of
      small effect size was found for three QoL domains using a then-test, which was
      confirmed in the domain of autonomy through statistical modelling. No evidence
      was found for reprioritisation or reconceptualisation RS using either analytical
      approach. CONCLUSION: The findings support the assumption that the
      conceptualisation of QoL is stable during adolescence in the absence of
      significant health threats. However, researchers and clinicians should be aware
      of potential recalibration effects of some life domains.

PMID- 18633731
TI  - Diabetes-induced atrophy is associated with a muscle-specific alteration in NF
      kappaB activation and expression.
AB  - NF-kappaB is a transcription factor implicated in pathological responses that
      develop during diabetes mellitus, including skeletal muscle atrophy. Given that
      NF-kappaB activation, protein composition, and content within diabetic skeletal
      muscle remain generally uncharacterized, a streptozotocin (STZ) model was used to
      assess NF-kappaB activation, composition, and content. Sprague-Dawley rats were
      injected with STZ (55 mg/kg) and after 30 days the soleus (SOL), plantaris (PL),
      red gastrocnemius (RG), and white gastrocnemius (WG) muscles were assessed by
      electrophoresis mobility shift assay and western blotting. NF-kappaB activation
      was detected in all muscles examined, but was reduced in RG muscles from diabetic
      animals. Supershifts indicated NF-kappaB was composed primarily of p50 in
      diabetic and control animals. The content of both p65 and p52 was elevated in SOL
      and PL muscles, while p52 was decreased in RG. The coactivating protein, Bcl-3,
      was increased in WG and RG, but decreased in PL. Both p50 and RelB remained
      unchanged in all tissues examined. All muscles from diabetic animals demonstrated
      reduced mass when compared to controls, but only the gastrocnemius demonstrated
      atrophy as reflected by a reduced muscle-to-body mass ratio. In conclusion,
      diabetic alterations to the contents and activation of the NF-kappaB protein were
      tissue-specific, but did not appear to alter dimer composition of constitutively
      bound NF-kappaB. These results indicate that diabetes may alter NF-kappaB
      activity and expression in a muscle-specific manner.

PMID- 18633732
TI  - Expression analysis and characteristics of profilin gene from silkworm, Bombyx
      mori.
AB  - A recombinant Bombyx mori profilin protein (rBmPFN) was overexpressed in
      Escherichia coli BL21. Purified rBmPFN was used to generate anti-BmPFN polyclonal
      antibody, which were used to determine the subcellular localization of BmPFN.
      Immunostaining indicated that profilin can be found in both the nucleus and
      cytoplasm but is primarily located in the cytoplasm. Real-time RT-PCR and Western
      blot analyses indicated that, during the larvae stage, profilin expression levels
      are highest in the silk gland, followed by the gonad, and are lowest in the fatty
      body. Additionally, BmPFN expression begins during the egg stage, increases
      during the larvae stage, reaches a peak during the pupa stage, and decreases
      significantly in the moth. Therefore, we propose that BmPFN may play an important
      role during larva stage development, especially in the silk gland.

PMID- 18633733
TI  - PVA-hydrogel entrapped Candida guilliermondii for xylitol production from
      sugarcane hemicellulose hydrolysate.
AB  - Viable cells of Candida guilliermondii were immobilized by inclusion into
      polyvinyl alcohol (PVA) hydrogel using the freezing-thawing method. Entrapment
      experiments were planned according to a 2(3) full factorial design, using the PVA
      concentration (80, 100, and 120 g L(-1)), the freezing temperature (-10, -15, and
      -20 degrees C), and the number of freezing-thawing cycles (one, three, and five)
      as the independent variables, integrated with three additional tests to estimate
      the errors. The effectiveness of the immobilization procedure was checked in
      Erlenmeyer flasks as the pellet capability to catalyze the xylose-to-xylitol
      bioconversion of a medium based on sugarcane bagasse hemicellulosic hydrolysate.
      To this purpose, the yield of xylitol on consumed xylose, xylitol volumetric
      productivity, and cell retention yield were selected as the response variables.
      Cell pellets were then used to perform the same bioconversion in a stirred tank
      reactor operated at 400 rpm, 30 degrees C, and 1.04 vvm air flowrate. At the end
      of fermentation, a maximum xylitol concentration of 28.7 g L(-1), a xylitol yield
      on consumed xylose of 0.49 g g(-1) and a xylitol volumetric productivity of 0.24
      g L(-1) h(-1) were obtained.

PMID- 18633734
TI  - Properties of a cationic peroxidase from Citrus jambhiri cv. Adalia.
AB  - The major pool of peroxidase activity is present in the peel of some Egyptian
      citrus species and cultivars compared to the juice and pulp. Citrus jambhiri cv.
      Adalia had the highest peroxidase activity among the examined species. Four
      anionic and one cationic peroxidase isoenzymes from C. jambhiri were detected
      using the purification procedure including ammonium sulfate precipitation,
      chromatography on diethylaminoethanol-cellulose, carboxymethyl-cellulose, and
      Sephacryl S-200 columns. Cationic peroxidase POII is proved to be pure, and its
      molecular weight was 56 kDa. A study of substrate specificity identified the
      physiological role of POII, which catalyzed the oxidation of some phenolic
      substrates in the order of o-phenylenediamine > guaiacol > o-dianisidine >
      pyrogallol > catechol. The kinetic parameters (K (m), V (max), and V (max)/K (m))
      of POII for hydrolysis toward H2O2 and electron donor substrates were studied.
      The enzyme had pH and temperature optima at 5.5 and 40 degrees C, respectively.
      POII was stable at 10-40 degrees C and unstable above 50 degrees C. The thermal
      inactivation profile of POII is biphasic and characterized by a rapid decline in
      activity on exposure to heat. The most of POII activity (70-80%) was lost at 50,
      60, and 70 degrees C after 15, 10, and 5 min of incubation, respectively. Most of
      the examined metal ions had a very slight effect on POII except of Li+, Zn2+, and
      Hg2+, which had partial inhibitory effects. In the present study, the instability
      of peroxidase above 50 degrees C makes the high temperature short time treatment
      very efficient for the inactivation of peel peroxidase contaminated in orange
      juice to avoid the formation of off-flavors.

PMID- 18633735
TI  - Two step purification of Acinetobacter sp. lipase and its evaluation as a
      detergent additive at low temperatures.
AB  - Acinetobacter sp. lipase was purified to homogeneity by a two-step process. The
      crude enzyme (along with biomass) was subjected to partial purification by
      aqueous two phase system (ATPS), avoiding centrifugation and filtration steps.
      Conditions for lipase partitioning by ATPS were optimized by response surface
      methodology (RSM) and a combination of 29.45% polyethylene glycol 8000, 15.5%
      phosphate, and a pH of 7.0 resulted in an optimal partition coefficient.
      Partially pure lipase was further purified by a modified batch process using
      Octyl Sepharose CL-4B in a vacuum filtration apparatus. This two-step process
      resulted in a purified lipase with a yield of 74.6% having a specific activity of
      88.8 U/mg of protein and a purification fold of 14.92. The homogeneity of the
      lipase preparation obtained by the purification process was confirmed by reversed
      phase high performance liquid chromatography profile. The molecular weight of the
      purified lipase was found to be around 32 kDa as determined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The purified lipase exhibited pH and
      temperature optima of 8.5 and 37 degrees C, respectively. The lipase was active
      at low temperatures and it retained 86.8% activity at 10 degrees C. It also
      displayed other features such as stability over a broad range of pH (3.0-9.0) as
      well as stability in the presence of hydrogen peroxide and commercial detergents.
      Based on these characteristics, the potential of this lipase as an additive in
      laundry detergent formulation was evaluated under low temperature wash
      conditions. The results indicated that Acinetobacter sp. lipase increased the
      washing efficiency of the detergent Nirma by 21-24% at 15 degrees C-20 degrees C,
      respectively.

PMID- 18633736
TI  - Effect of agitation and aeration rates on chitinase production using Trichoderma
      virens UKM1 in 2-l stirred tank reactor.
AB  - Shrimps have been a popular raw material for the burgeoning marine and food
      industry contributing to increasing marine waste. Shrimp waste, which is rich in
      organic compounds is an abundant source of chitin, a natural polymer of N-acetyl
      D-glucosamine (GluNac), a reducing sugar. For this respect, chitinase-producing
      fungi have been extensively studied as biocontrol agents. Locally isolated
      Trichoderma virens UKM1 was used in this study. The effect of agitation and
      aeration rates using colloidal chitin as control substrate in a 2-l stirred tank
      reactor gave the best agitation and aeration rates at 200 rpm and 0.33 vvm with
      4.1 U/l per hour and 5.97 U/l per hour of maximum volumetric chitinase activity
      obtained, respectively. Microscopic observations showed shear sensitivity at
      higher agitation rate of the above system. The oxygen uptake rate during the
      highest chitinase productivity obtained using sun-dried ground shrimp waste of
      1.74 mg of dissolved oxygen per gram of fungal biomass per hour at the kappaL a
      of 8.34 per hour.

PMID- 18633738
TI  - Depressed patients' acceptability of the use of self-administered scales to
      measure outcome in clinical practice.
AB  - BACKGROUND: Self-report questionnaires are a cost-effective option to monitor the
      outcome of clinical care. Even when using self-report scales, consideration
      should be given to how much time they take to complete and how burdensome they
      are perceived to be. In the present report from the Rhode Island Methods to
      Improve Diagnostic Assessment and Services (MIDAS) project, we compared the
      acceptability of completing two depression scales-the Beck Depression Inventory
      (BDI) and the Clinically Useful Depression Outcome Scale (CUDOS). METHODS: In the
      first study, 50 depressed psychiatric outpatients completed the CUDOS and a
      questionnaire assessing how burdensome it was to complete during the visit. In
      the second study, a separate sample of 50 depressed outpatients completed the
      CUDOS and BDI and a measure of scale acceptability. RESULTS: Almost all patients
      completed the CUDOS in less than 3 minutes (mean = 102.7 seconds, SD = 42.7) and
      considered the questionnaire very little or a little burdensome (98.0%, n = 49).
      In the second study comparing the CUDOS and the BDI, significantly more patients
      indicated that the CUDOS took less time to complete and was less of a burden to
      complete. Nearly three times as many patients indicated that they would prefer to
      complete the CUDOS in order to monitor the outcome of treatment (40.0% vs. 14.0%,
      z = 2.31, p .05). CONCLUSIONS: A consumer-friendly, reliable, and valid self
      administered questionnaire can improve the efficiency of the clinical encounter.
      The brevity of the CUDOS lends itself to regular administration in clinical
      practice.

PMID- 18633737
TI  - Effect of neuregulin on apoptosis and expressions of STAT3 and GFAP in rats
      following cerebral ischemic reperfusion.
AB  - The aim is to investigate the effect of neuregulin-1beta (NRG-1beta) on the
      neuronal apoptosis and the expressions of signal transducer and activator of
      transcription (STAT3) and glial fibrillary acidic protein (GFAP) in rats
      following cerebral ischemia/reperfusion. The animal models of middle cerebral
      artery occlusion/reperfusion (MCAO/R) were established by an intraluminal
      filament method from left external-internal carotid artery in 100 cases of adult
      healthy male Wister rats. NRG-1beta was administered from the internal carotid
      artery (ICA) into MCA in the treatment group. The neuronal apoptosis was detected
      by terminal deoxynucleotidyl transference-mediated biotinylated deoxyuridine
      triphosphate nick-end labeling technique. The expression alternations of STAT3
      and GFAP proteins were determined by fluorescent labeling analysis and Western
      blotting assay. Ischemic cerebral injury could induce neuronal apoptosis.
      Furthermore, with the duration of ischemia, the amount of apoptotic cells
      increased in the control group. These apoptotic cells distributed in various
      brain regions, especially the cortex, striatum, and hippocampus, while only a
      small amount of apoptotic cells could be observed in the treatment group, and
      there were significant differences compared with that in the control group (P <
      0.01). The expressions of STAT3 and GFAP proteins in brain tissue gradually
      increased in the control group with the duration of ischemia. And NRG-1beta could
      elevate the expressional level of STAT3 and GFAP proteins in contrast to the
      control group (P < 0.05). NRG-1beta may play a neuroprotective role in cerebral
      ischemic insult by activating JAK/STAT signal transduction pathway, promoting the
      astrocyte gumnosis and regulating the anti-apoptosis mechanism in neurocytes.

PMID- 18633740
TI  - The impact of olanzapine on tardive dyskinetic symptoms in a state hospital
      population.
AB  - BACKGROUND: Tardive dyskinesia is a serious adverse event, which is associated
      mainly with the use of the first-generation antipsychotic agents. Convergent data
      from clinical trials suggest that second-generation antipsychotic agents are less
      likely to cause tardive dyskinesia. However, the data with regard to the effect
      of switching from first- to second-generation antipsychotic agents on pre
      existing dyskinetic symptoms during routine clinical care is sparse. METHODS:
      Sixty-three patients with DSM-IV schizophrenia or schizoaffective disorder (n =
      61) or bipolar I disorder (n = 2) consecutively admitted to a state hospital, who
      were treated either with olanzapine (n = 35) or conventional antipsychotic agents
      (n = 28) by physician choice, were enrolled in the study. The severity and
      frequency of tardive dyskinetic symptoms using the Abnormal Involuntary Movement
      Scale were assessed in the two medication groups at baseline, 8 weeks, and 6
      months. RESULTS: There were statistically significant reductions in the
      prevalence and severity of dyskinetic symptoms at 8 weeks and 6 months for the
      group treated with olanzapine but not for those treated with conventional agents.
      CONCLUSIONS: These preliminary data suggest that olanzapine may be a treatment
      option for subjects with tardive dyskinesia. However, the question whether
      olanzapine treats, ameliorates, or masks preexisting tardive dyskinesia was
      difficult to answer, as no dosage reduction or withdrawal was undertaken.

PMID- 18633739
TI  - Elevated prevalence of obesity, metabolic syndrome, and cardiovascular risk
      factors in bipolar disorder.
AB  - BACKGROUND: Bipolar disorder is associated with excess cardiovascular mortality.
      We hypothesized outpatients with bipolar disorder would exhibit excess
      cardiovascular risk factors, particularly among prevalent users of the second
      generation antipsychotics associated with weight gain and valproic acid
      derivatives. METHODS: This chart review of 217 patients with bipolar disorder
      examined cardiovascular risk factors of the metabolic syndrome. We also evaluated
      if certain medications were cross-sectionally associated with metabolic syndrome.
      RESULTS: Fifty-six patients were not weighed and many did not have available
      lipid profiles. Over three-quarters of those with available data (n = 161) were
      overweight or obese (body mass index >or= 25) and nearly half were obese (body
      mass index >or= 30). A prevalence exceeding general population estimates was also
      observed for hypertriglyceridemia, elevated blood pressure/hypertension, and
      elevated fasting glucose/diabetes. Among those with all requisite data (n = 60),
      over 50% met criteria for National Cholesterol Education Program-defined
      metabolic syndrome, nearly double the expected prevalence. A trend toward greater
      prevalence of metabolic syndrome among prevalent users of the second-generation
      antipsychotics associated with weight gain was observed. CONCLUSIONS: Obesity and
      the metabolic syndrome were common in patients with bipolar disorder. These
      patients may be under-evaluated for cardiovascular risk and warrant screening and
      early intervention.

PMID- 18633741
TI  - Pharmacotherapy for methamphetamine dependence: a review of the pathophysiology
      of methamphetamine addiction and the theoretical basis and efficacy of
      pharmacotherapeutic interventions.
AB  - BACKGROUND: Methamphetamine (METH) dependence is a significant public health,
      criminal justice, and social service concern, and although abuse of this drug
      spans the past 40 years in the U.S., effective treatments have only recently been
      developed and evaluated. Psychosocial therapies comprise the mainstay of
      treatment, yet many patients experience ongoing impairments in mood, cognition,
      emotional control, and motivation, suggesting a role for pharmacotherapy.
      METHODS: A search of the literature was performed to identify drug therapies
      utilized with METH dependent patients and the outcome of these trials. RESULTS:
      With the exception of bupropion, most trials employing direct monoamine agonists
      yielded negative or inclusive results, a counterintuitive finding. Positive
      results were produced by a trial of the mixed monoamine agonist/antagonist
      mirtazapine and by several studies employing indirect dopamine- and glutamate
      modulating GABA agonists. Most trials were hampered by high rates of subject
      attrition, mirroring the difficulty in treating these patients in the outpatient
      setting. CONCLUSIONS: Although considered preliminary, several therapeutic agents
      were identified that may prove beneficial in treating METH-dependent patients,
      including bupropion, mirtazapine, baclofen, and topiramate. Psychosocial therapy
      remains the cornerstone of treatment, and drug therapy should be regarded as an
      adjunct, rather than a replacement for psychosocial approaches.

PMID- 18633742
TI  - Does acute treatment with sedatives/hypnotics for anxiety in depressed patients
      affect suicide risk? A literature review.
AB  - BACKGROUND: Anxiety (among several other symptoms) has been identified in one
      prospective study as associated with suicide risk in depressed patients early in
      treatment. It has been suggested that treatment of anxiety in depression with
      sedative/hypnotic agents, especially benzodiazepines, in the first several weeks
      may decrease suicide risk. Sedative/hypnotic agents also have depressant and
      disinhibitory properties which might increase suicide risk, however. This review
      addresses the potential benefits and risks with regard to suicide of using
      sedative/hypnotics as an early adjunct to antidepressant treatment in anxious
      depressed patients. METHODS: Pertinent medical literature was reviewed using
      Medline/PubMed search as well as bibliographies from related publications.
      Reports in English from 1958 to 2006 were included. RESULTS: The review did not
      reveal any evidence that using sedative/hypnotics as an early adjunct to
      antidepressant treatment of anxious depressed patients decreases their suicide
      risk. There is considerable evidence that sedative/hypnotics produce depressant
      and/or disinhibitory effects in a small proportion (perhaps 5%) of people who
      take them. However, there is no clear evidence that their brief use early in
      depression increases suicide risk. Toxicological data of suicides indicate that a
      majority of people who commit suicide are under the influence of
      sedative/hypnotic chemicals (including alcohol) at the time. CONCLUSIONS: The
      authors conclude that the question of whether sedative/hypnotics may prevent or
      provoke suicide in anxious depressed patients cannot be answered definitively
      with the available information. They believe the potential risks of prescribing
      sedative/hypnotics for depressed patients who may be suicidal are serious. They
      suggest that alternatives to sedative/hypnotics should be used if early
      adjunctive treatment for anxiety in depressed patients is thought to be
      indicated.

PMID- 18633743
TI  - Depression cured by stroke.

PMID- 18633744
TI  - Carisoprodol withdrawal syndrome misdiagnosed as a psychotic disorder.

PMID- 18633745
TI  - Shock-like sensations associated with duloxetine discontinuation.

PMID- 18633753
TI  - HOMA-estimated insulin resistance is associated with hypertension in Iranian
      diabetic and non-diabetic subjects.
AB  - The relationship between insulin resistance (IR) and essential hypertension (HTN)
      is controversial. The aim of this study was to determine the association of IR
      estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and HTN
      in a large sample of Iranian diabetic and non-diabetic population. A total of
      2047 diabetic and non-diabetic individuals with or without HTN, aged 30-75 yrs,
      who were referred to a university general hospital between November 2004 and
      April 2007 were included in this study. Demographic data and anthropometric
      characteristics of participants were recorded. Fasting blood samples were
      collected, and fasting plasma glucose (FPG), serum creatinine, lipids, insulin, C
      peptide and HbA1c were measured. HOMA-IR and HOMA derived Beta-cell function
      (HOMA-B) were also calculated. Age, sex and waist girth adjusted HOMA-IR values
      were compared between hypertensive and normotensive subjects. Hypertensive
      patients had significantly higher HOMA-IR than age-, sex-, and waist girth
      adjusted normotensive individuals in both non-diabetic (2.163 +/- 0.08 and 1.75
      +/- 0.03, p < 0.001) and diabetic (3.40 +/- 0.10 and 3.07 +/- 0.09, p < 0.05)
      groups. Multivariate logistic regression analysis showed that after adjustment
      for age, sex, waist girth, BMI, triglyceride, total cholesterol, FPG, and C
      peptide, HOMA-IR was a significant independent predictor of HTN in all subjects
      (odds ratio = 1.117, CI 95% = 1.026-1.216, p < 0.05) and in diabetic and non
      diabetic subjects separately (odds ratio = 1.102, CI 95% = 1.009-1.203, p < 0.05
      and odds ratio = 1.328, CI 95% = 1.116-1.580, p < 0.01, respectively). In
      conclusion, this study showed that IR is associated with HTN in Iranian diabetic
      and non-diabetic subjects.

PMID- 18633754
TI  - Improved early-phase insulin response after candesartan treatment in hypertensive
      patients with impaired glucose tolerance.
AB  - As the effect of renin-angiotensin system (RAS) blockade on beta-cells in
      clinical situations remains unclear, new evidence has been presented that
      angiotensin-converting enzyme (ACE) inhibitors and angiotensin vertical line
      vertical line receptor blockers (ARBs) may delay or prevent the development of
      insulin resistance and diabetes through novel mechanisms. This study aimed to
      determine the effects of ARBs on insulin excretion by beta-cells. Hypertensive
      patients with impaired glucose tolerance were randomly divided into two groups:
      group A (n = 6), which received 8 mg/day of oral candesartan for three months,
      and controls (n = 6). Before and after administration, a 75 g oral glucose
      tolerance test was conducted to compare various parameters. No significant
      differences in age, body mass index (BMI), systolic blood pressure (SBP),
      diastolic blood pressure (DBP), fasting glucose, or fasting immunoreactive
      insulin (IRI) were identified between the groups before administration. After
      three months, there were no significant changes in BMI, SBP, and DBP for the
      controls and in BMI and DBP for group A. However, SBP was significantly decreased
      from 144 +/- 2.6 mmHg to 125 +/- 4.6 mmHg in group A. Insulinogenic index tended
      to be slightly decreased for controls, but was significantly increased from 0.32
      +/- 0.0 to 0.47 +/- 0.1 for group A. No significant changes in HOMA-R were
      identified in either group. To the best of our knowledge, no previous studies
      have documented a RAS inhibitor improving early-phase insulin response; thus, the
      present study may be the first of its kind.

PMID- 18633755
TI  - Comparative analysis of renal protein expression in spontaneously hypertensive
      rat.
AB  - OBJECTIVE: Molecular mechanisms of nephrosclerosis caused by hypertension are not
      well known. Understanding changes in renal protein expression in hypertension may
      provide further information on how hypertension caused renal injury. METHODS AND
      RESULTS: In the present study, we showed the protein expression profiles of the
      kidney in spontaneously hypertensive rats and Wistar-Kyoto rats using two
      dimensional gel electrophoresis (2-DE). Differentially expressed protein spots
      were excised, underwent in-gel tryptic digestion, and were analyzed by MALDI-TOF
      MS. Eleven spots were identified. Of these identified spots, four spots were
      newly appeared, five spots up-regulated, and two spots down-regulated. The
      identified spots were mainly involved in energy metabolism, lipid transferring
      between membranes, and cell proliferation. CONCLUSIONS: The expression of many
      proteins have changed significantly in the kidney of spontaneously hypertensive
      rat. NADP(+)-dependent isocitrate dehydrogenase may be a candidate for further
      investigation of pathophysiological mechanisms of renal injury in hypertension.

PMID- 18633756
TI  - Gender-specific differences in hypertension prevalence, treatment, control, and
      associated conditions among the elderly: data from a Greek population.
AB  - PURPOSE: In the present study we sought to assess the gender-specific prevalence,
      treatment rates, and control of hypertension, as well as to identify its
      associated conditions and additional cardiovascular (CV) risk factors, in a Greek
      population aged > or = 65 years old. METHODS: This is a population-based study
      including a clinical interview, an ECG recording, and blood pressure (BP)
      measurements by sphygmomanometer. RESULTS: The overall prevalence of hypertension
      was 83.3%, higher in females and increasing with age. In males, hypertension was
      independently associated with increased body mass index (BMI), a history of
      stroke, and myocardial infarction, while in females increased age, BMI, and a
      history of diabetes were independently associated with hypertension. A
      considerable proportion of hypertensives were treated (77.3%), while an effective
      control of BP was achieved in 42.5% of treated subjects. Despite the fact that
      hypertension treatment rates did not differ between the genders, control rates
      were lower among females. Finally, more hypertensive females presented additional
      CV risk factors than normotensives. CONCLUSION: Elderly females exhibit a higher
      prevalence of hypertension and are characterized by lower hypertension control
      compared to hypertensive males.

PMID- 18633757
TI  - Is Ramadan fasting safe in type 2 diabetic patients in view of the lack of
      significant effect of fasting on clinical and biochemical parameters, blood
      pressure, and glycemic control?
AB  - The study objective was to determine if Ramadan fasting was safe in patients with
      type 2 diabetes mellitus (T2D), based upon a determination of the effect of
      fasting on a broad range of physiological and clinical parameters, including
      markers of glycemic control and blood pressure. The study was carried out in
      Ramadan 1422 (December 2001-January 2002) at the Diabetology Services, Hopital
      Ibn Sina, Rabat, Morocco. One hundred and twenty T2D Moroccan patients (62 women,
      58 men), aged 48-60 yrs with well-controlled diabetes through diet and/or oral
      hypoglycemic drugs (OHD), received dietary instructions and readjustment of the
      timing of the dose of OHD (gliclazide modified release) according to the
      fasting/eating periods. Anthropometric indices and physiological parameters
      (blood pressure, lipid, hematological, and serum electrolyte profiles, as well as
      markers of glycemic control, nutrition, renal and hepatic function) were measured
      on the day before Ramadan and then on the 15(th) and 29(th) day of fasting and
      thereafter 15 days later. Statistical analysis was done by standard methods.
      Ramadan fasting had no major effect on energy intake, body weight, body mass
      index, blood pressure, and liver enzymes. Fasting and post-prandial glucose
      levels decreased, while insulin levels increased. Diabetes was well controlled,
      as indicated by HbA1c, fructosamine, C-peptide, HOMA-IR, and IGF-1 values. There
      were fluctuations in some lipid and hematological parameters, creatinine, urea,
      uric acid, total protein, bilirubin, and electrolytes; however, all values stayed
      within the proper physiological range. In conclusion, diabetes was well
      controlled in patients with dietary/medical management, without serious
      complications. With a regimen adjustment of OHD, diet control, and physical
      activity, most patients with T2D whose diabetes was well-controlled before
      Ramadan can safely observe Ramadan fasting.

PMID- 18633758
TI  - Identification of hypertension and efficacy of treatment in a rural Australian
      population.
AB  - High blood pressure leads to greater risk of cardiovascular disease morbidity and
      mortality. Our aim was to determine the prevalence of hypertension in a cohort of
      people attending a rural university health screening program in response to
      community advertisements. In all, 674 individuals attended the screening program
      at our university health clinic in Albury. The presence and treatment of
      diagnosed hypertension were reported by 37.3% of participants. Antihypertensive
      medications were used in 42.9% of the known hypertensives, and fewer than half of
      these patients on antihypertensive agents achieved a normal blood pressure. New
      hypertension in accordance with the AusDiab criteria that is not diagnosed and
      treated was identified in 20.8% of participants. We conclude that the rates of
      antihypertensive treatment were low in this rural population, and that in those
      who were treated, a large portion still remained hypertensive. The management and
      monitoring of hypertension in this rural community needs to be improved to
      capture the additional people with hypertension and to reduce blood pressure to
      recommended levels.

PMID- 18633759
TI  - Association between protein bound sialic acid and high sensitivity C-reactive
      protein in prehypertension: a possible indication of underlying cardiovascular
      risk.
AB  - The global burden posed by cardiovascular disease due to a rising incidence of
      known risk factors like essential hypertension underlines an urgent need to
      identify other potential risk factors like dyslipidemia, elevated levels of high
      sensitivity CRP (hsCRP), Apo-B, and sialic acid in prehypertensive subjects. This
      study sought to examine the possible alteration in the levels of hsCRP, plasma
      protein bound sialic acid, and other lipid risk factors and the possible
      interactions among these parameters in prehypertensive subjects. Forty
      prehypertensive and 34 normotensive male subjects were enrolled in the study.
      Lipid profile, hsCRP, Apo-B, sialic acid, and lipid risk ratios were estimated in
      both the groups. There was no significant difference between fasting glucose and
      BMI in either group. The levels of total cholesterol, triglycerides, direct LDL
      cholesterol, non-HDL cholesterol, and Apo-B were significantly increased in
      prehypertensive subjects compared with controls. The risk ratios calculated as
      direct LDL-cholesterol/Apo-B, total cholesterol/HDL-cholesterol, non-HDL
      cholesterol/HDL-cholesterol were significantly elevated in prehypertensive
      subjects. There was also a significant increase in hsCRP and protein bound sialic
      acid in prehypertensive subjects in comparison with normotensive subjects.
      Correlation analysis revealed a significant association between the protein bound
      sialic acid with hsCRP, LDL cholesterol, and LDL-C/Apo-B. The findings of the
      present study suggest that in prehypertension, there is an association between
      protein bound sialic acid and hsCRP that reflects the clustering of
      cardiovascular risk factors in these subjects.

PMID- 18633760
TI  - Multifocal electroretinogram in mild to moderate essential hypertension.
AB  - PURPOSE: To investigate the local retinal dysfunctions in mild to moderate
      essential hypertensive patients by using multifocal electroretinogram (mfERG).
      METHODS: Thirty-one patients with stage 1 or stage 2 hypertension (HT) and 31 age
      and sex-matched healthy normotensive (NT) subjects were included. Fourteen of
      the patients had stage 1 and 17 had stage 2 hypertension. Twenty had grade 1 and
      11 had grade 2 hypertensive retinopathy. The local retinal functions from the
      fovea to the peripheral 30 degrees were evaluated by multifocal electroretinogram
      by dividing this area to central hexagonal area (CH) and four concentric rings
      around the central hexagon (Rings 1-4). The amplitude and the implicit times of
      the positive peak (P1) and the negative peak (N1) of the responses were compared
      between the control subjects and hypertensive patients. Only the right eyes were
      included. The differences between the hypertensive patients and control subjects
      were investigated using independent samples t test, and the differences between
      grade 1 and grade 2 hypertensive retinopathy and stage 1 and stage 2 hypertension
      were investigated using Mann-Whitney U test. RESULTS: P1 amplitudes in CH (HT:
      129.0 +/- 29.5, NT: 149.1 +/- 45.5, p = 0.043) and in Ring 3 (HT: 37.0 +/- 8.0,
      NT: 41.7 +/- 7.8, p = 0.024) and N1 amplitude in Ring 1 (HT: 26.8 +/- 7.4, NT:
      30.8 +/- 7.8, p = 0.048) in the hypertensive patients was significantly reduced
      when compared to healthy normotensive subjects. There was no significant
      difference in terms of P1 and N1 implicit times. There was also no significant
      difference between the patients with stage 1 or stage 2 hypertension and patients
      with grade 1 or grade 2 hypertensive retinopathy. CONCLUSION: Hypertensive
      subjects have local retinal dysfunctions with respect to healthy controls. This
      result probably originated from retinal ischemia due to changes in retinal and/or
      choroidal circulation in systemic arterial hypertension.

PMID- 18633761
TI  - Reductions in blood pressure following energy restriction for weight loss do not
      rebound after re-establishment of energy balance in overweight and obese
      subjects.
AB  - OBJECTIVE: The objective of the present study was to elucidate the separate
      effects of energy restriction and weight loss on blood pressure (BP) and to
      assess the relationship between sodium intake, weight loss, and BP. METHODS: Two
      hundred and eight overweight and obese subjects (age: 52.4 +/- 0.8 yrs; BMI 33.6
      +/- 0.3 kg/m(2)) completed a weight loss diet program consisting of 8-12 weeks of
      moderate energy restriction (ER; approximately 30% energy deficit, unrestricted
      salt intake) and four weeks of energy balance (EB). Body weight and BP were
      measured at baseline, the midpoint, and the end of ER and after EB. 24-hr Na+
      excretion was measured at baseline and at the end of EB. RESULTS: Overall, body
      weight reduced progressively by 7.0 +/- 0.2 kg (7.5%; p < 0.001) with the
      hypocaloric diet. BP fell substantially during the first phase of ER (-5.7 +/-
      0.7/-2.6 +/- 0.4 mmHg, p = 0.001), corresponding to a 4.5 +/- 0.2 kg weight
      reduction, with no further BP changes during the second phase of ER, despite
      further weight loss (2.4 +/- 0.1 kg). During EB, BP remained stable. The
      hypotensive effects of caloric restriction and weight loss were similar across
      clinical subgroups defined by age, sex, diabetes, insulin sensitivity, and
      hypertensive status. BP responses to weight loss were independent of 24-hr
      urinary Na+ excretion. 24-hr urinary Na+ excretion was similar at baseline and at
      the end of EB (146.5 +/- 5.3 vs. 146.9 +/- 5.3 mmol/24-hr). CONCLUSION: The
      hypotensive effects of caloric restriction do not rebound upon return to
      eucaloric intake at a reduced body weight, and a high sodium intake does not
      appear to alter the hypotensive effects of weight loss. This reinforces the
      clinical importance of weight loss and supports the recommendation that
      strategies for promoting long-term weight loss should become the primary focus of
      dietary efforts to control BP in overweight patients.

PMID- 18633762
TI  - The importance of integrated risk management when treating patients with
      hypertension: benefits of angiotensin II receptor antagonist therapy.
AB  - Hypertension is an important risk factor for cardiovascular disease (CVD),
      particularly in patients with comorbid obesity, diabetes, metabolic disease, or
      end-organ damage. An integrated CV risk management approach is being adopted:
      aggressive blood pressure (BP) control is important in patients with high CVD
      risk, and well-tolerated antihypertensive agents with protective benefits beyond
      BP lowering are advantageous. The renin-angiotensin system is integral to blood
      pressure control and is well established in the pathophysiology of CVD.
      Angiotensin II receptor blockers (ARBs) are highly efficacious, persistent, well
      tolerated antihypertensive agents, with additional benefits in comorbid
      hypertension, CV pathologies, end-organ damage, and, in diabetes, diabetic
      nephropathy or metabolic syndrome. ARBs decrease overall risk of CV and end-organ
      disease, CVD-related mortality, and cerebrovascular events in patients with
      hypertension.

PMID- 18633763
TI  - Long-term effects of angiotensin II receptor blockade with valsartan on carotid
      arterial stiffness and hemodynamic alterations in patients with essential
      hypertension.
AB  - Increased arterial stiffness and intima media thickness (IMT) in the common
      carotid artery (CCA) are related to cardiovascular risk in essential
      hypertension. Angiotensin II plays an important role in structural and functional
      changes in the vasculature. In this study, we evaluated the long-term effect of
      the angiotensin II receptor blocker, valsartan, on IMT, arterial stiffness, and
      hemodynamics in the CCA in patients with essential hypertension. A prospective 24
      month study of treatment with valsartan (80-160 mg/day) was performed in 24
      hypertensive patients. An ultrasound of the CCA was carried out to determine IMT,
      the cross-sectional distensibility coefficient (CSDC), the carotid arterial
      stiffness index beta, and diastolic flow velocity to systolic flow velocity ratio
      (Vd/Vs). Treatment with valsartan for 24 months reduced systolic and diastolic
      blood pressure significantly. Compared to baseline, the decrease in pulse
      pressure was greater after 24 months treatment than after 12 months treatment.
      Valsartan did not influence IMT; however, after 24 months, it caused a
      significant increase in CSDC and a decrease in stiffness index beta compared to
      baseline. These changes were not observed after 12 months of treatment. In
      addition, Vd/Vs, a sensitive marker of relative diastolic blood flow, increased
      after 24 months' treatment with valsartan. These results suggest that long-term
      treatment with valsartan improves vascular wall function and hemodynamics in
      patients with essential hypertension.

PMID- 18633764
TI  - The effect of enalapril and telmisartan on clinical and biochemical indices of
      sympathetic activity in hypertensive patients.
AB  - OBJECTIVE: To compare the effect of ARB and ACE inhibitor on sympathetic activity
      in 32 hypertensives. DESIGN AND METHODS: After a four-week wash-out period,
      patients were randomized to four weeks of therapy with enalapril or telmisrtan,
      with crossover to another drug for another four weeks. Blood pressure (BP), NPY,
      and catecholamine levels and HRV (frequency analysis) were measured during wash
      out, in basal condition, and after postural stimulation test (PST). RESULTS: Both
      drugs significantly reduced BP and NPY as compared to initial values, while no
      differences in BP and NPY between drugs were observed. Increase in NPY during PST
      was significantly higher in the enalapril than in the telmisartan group and
      during the wash-out period. No differences between enalapril and telmisartan in
      plasma catecholamines were observed. Telmisartan decreased low frequency/high
      frequency ratio as compared to initial values and enalapril values. CONCLUSIONS:
      Despite similar BP control, telmisartan attenuated autonomic balance more
      effectively than enalapril.

PMID- 18633765
TI  - Fetal peritonitis due to appendiceal rupture: a rare complication of hydrops.
AB  - A rare complication (appendiceal perforation with meconium peritonitis) was
      observed in a second trimester fetus affected by nonimmune fetal hydrops due to
      parvovirus B-19 infection. The complication is not considered specific to this or
      any other etiology for hydrops, which is highly heterogeneous; rather it is an
      expression of the fragility and friability of edematous tissues.

PMID- 18633766
TI  - Alveolar capillary dysplasia: absence of CD117 immunoreactivity of putative
      hemangioblast precursor cells.
AB  - Alveolar capillary dysplasia is a rare cause of irreversible persistent pulmonary
      hypertension in newborns resulting from failure of formation of peripheral
      capillary loops with consequent reduction in the blood-gas barrier. The basic
      defect in morphogenesis is unknown, although it is postulated that there is a
      structural abnormality of the hemangioblast precursors of the primitive lung
      mesenchyme in the septal regions of the developing lung leading to abnormal
      vasculogenesis. Two cases of alveolar capillary dysplasia evaluated
      immunohistochemically showed uniform CD117 negativity in the septal interstitial
      cells forming the pulmonary capillaries. A series of 12 control cases showed
      positive immunoreactivity for CD117 in a subset of septal interstitial cells
      forming the putative hemangioblast precursor cells. This novel finding is a
      useful adjunctive diagnostic tool and may support the hypothesis that absence of
      putative CD117-positive hemangioblast precursor cells is a key structural defect.
      This defect results in abnormal vasculogenesis and consequent failure of
      formation of an adequate blood-gas barrier.

PMID- 18633767
TI  - Simple (unicameral) bone cyst of the calcaneus: a pathologic variant revisited.
AB  - A 17-year-old girl was admitted to the hospital for surgery of an enlarging,
      painful mass of the left calcaneus. Preoperative imaging studies suggested either
      a simple (unicameral) or aneurysmal bone cyst. Intraoperative biopsy of the
      lesion revealed a simple bone cyst with extensive cholesterol clefts. Such cysts
      are not uncommon in the calcaneus. However, the pathology of this case is unusual
      and often overlooked. The typical presentation, treatment, and pathology of these
      lesions are reviewed.

PMID- 18633768
TI  - TNF-alpha and IL-10 gene polymorphisms versus cardioimmunological responses in
      sudden infant death.
AB  - We hypothesized that genetic variations of cytokines could contribute to the risk
      of developing a fatal immunological reaction in the heart of infants. Thus, tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-10 gene polymorphisms versus
      induction of cardioimmunologxical responses in victims of sudden infant death
      syndrome (SIDS) were explored. We genotyped 35 infants (23 cases of SIDS and 12
      infants with a known cause of death), and 100 healthy adult controls for IL-10 
      1082 G/A, -592 C/A and TNF-alpha-238 G/A, -308 G/A. We found a higher frequency
      of the ATA haplotype and ATA/ATA genotype of IL-10 associated with SIDS (13%).
      The frequency of homozygote infants for IL-10 haplotypes in SIDS was higher (52%)
      than the control group (34%). All SIDS cases were homozygotice for the TNF-alpha
      238 G allele and 20 infants were homozygous for the TNF-alpha-308 G allele in the
      same group. None of the infants with higher levels of infiltrated T-cells (n=8)
      was homozygous for IL-10 gene polymorphisms, whereas in contrast 3 cases of the 6
      that displayed higher levels of cardiac mast cells were homozygous. In this
      study, the increased number of interstitial T-cells, mast cells, and macrophages
      in the myocardial interstitium demonstrated no correlation with the genotype for
      either cytokines.

PMID- 18633769
TI  - Clinicopathologic conference: Pulmonary tumor in a thirteen-year-old child.
AB  - An inflammatory myofibroblastic tumor as a distinct clinicopathologic entity in
      the lung has gained wide acceptance. The majority of these tumors are either
      contained within a single segment or pulmonary lobe and may cross the interlobar
      fissure and/or extend into the mediastinum, especially if arising in a perihilar
      location. We describe the case of a 13-year-old male with a 4-year history of an
      unresponsive lung mass in the left hemithorax. The resected tumor showed the
      typical morphology of a fasciculated fibroblastic/myofibroblastic lesion.

PMID- 18633770
TI  - Primary angiosarcoma of the brain in a child.
AB  - We describe a pediatric case of primary angiosarcoma of the brain displaying
      striking intravascular papillary pattern, consistent with the "Dabska tumor,"
      often in continuity with a massive, multifocal intravascular papillary
      endothelial hyperplasia. The tumor contained small hemangioma and obliterated
      dysplastic arteries as well as very large thin-walled veins. The surrounding
      brain tissue showed scattered telangiectasias, conglomerates of calcified
      dysplastic arteries, old hemorrhages and gliosis. Colocalization of these lesions
      suggests the development of a papillary angiosarcoma in the pre-existing vascular
      malformation. Although never reported, the possibility of a malignant
      transformation of endothelial papillary hyperplasia also should be considered in
      this case.

PMID- 18633771
TI  - Social Neuroscience: a new journal.

PMID- 18633772
TI  - The good, the bad, and the ugly: an fMRI investigation of the functional anatomic
      correlates of stigma.
AB  - Social interactions require fast and efficient person perception, which is best
      achieved through the process of categorization. However, this process can produce
      pernicious outcomes, particularly in the case of stigma. This study used fMRI to
      investigate the neural correlates involved in forming both explicit ("Do you like
      or dislike this person?") and implicit ("Is this a male or female?") judgments of
      people possessing well-established stigmatized conditions (obesity, facial
      piercings, transsexuality, and unattractiveness), as well as normal controls.
      Participants also made post-scan disgust ratings on all the faces that they
      viewed during imaging. These ratings were subsequently examined (modeled
      linearly) in a parametric analysis. Regions of interest that emerged include
      areas previously demonstrated to respond to aversive and disgust-inducing
      material (amygdala and insula), as well as regions strongly associated with
      inhibition and control (anterior cingulate and lateral prefrontal cortex).
      Further, greater differences in activation were observed in the implicit
      condition for both the amygdala and prefrontal cortical regions in response to
      the most negatively perceived faces. Specifically, as subcortical responses
      (e.g., amygdala) increased, cortical responses (e.g., lateral PFC and anterior
      cingulate) also increased, indicating the possibility of inhibitory processing.
      These findings help elucidate the neural underpinnings of stigma.

PMID- 18633773
TI  - Functional connectivity with the anterior cingulate is associated with
      extraversion during the emotional Stroop task.
AB  - Previous research has investigated the association of personality traits with
      brain activation in response to emotional stimuli. Our current research efforts
      are directed at understanding the temporal dynamics of networks of structures
      associated with particular personality traits, and gain insights into the
      functional contributions of more narrowly defined trait-facets that comprise
      these personality traits. To begin this process, we conducted a functional
      magnetic resonance imaging (fMRI) study using an emotional attention task
      (emotional Stroop paradigm) and addressed the question whether individual
      differences in extraversion and its lower-level facets were associated with
      differences in activation, and in functional connectivity, of the anterior
      cingulate (AC) cortex. We replicated our earlier finding that extraversion was
      associated with increased AC activation to positive, relative to neutral, word
      stimuli, but now show that distinct facets of extraversion can account for this
      association. When analyzing for functional connectivity, we found that greater
      extraversion across individuals was associated with greater functional
      connectivity between the AC and the inferior parietal lobule, and that this
      association could also be accounted for by distinct facets of extraversion. Our
      data suggest that extraversion and some of its lower-level facets are associated
      with individual differences across a network of structures believed to be
      critical in cognitive and affective processing.

PMID- 18633774
TI  - Self-related processing in the sexual domain: a parametric event-related fMRI
      study reveals neural activity in ventral cortical midline structures.
AB  - Self-related processing, reflecting the evaluation of environmental signals with
      regard to personal relevance, is fundamental for decision-making and subsequent
      behavioral responses. While self-related processing has already been investigated
      in several domains, one important domain, the sexual domain, has been spared so
      far. Recent imaging studies suggest that self-related processing in different
      domains involves common regions in medial orbitofrontal and prefrontal cortex,
      the so-called ventral cortical midline structures (CMS). However, the same
      regions have also been implicated in sexual arousal, especially with regard to
      emotional processing in sexual arousal. Therefore it remains unclear whether this
      involvement of ventral cortical midline regions reflects emotional processing in
      sexual arousal or associated self-relatedness. We here report data from a
      parametric event-related fMRI study that investigated the neural correlates of
      self-related processing in sexual arousal, using erotic pictures from the
      International Affective Picture System. It was found that self-related activity
      associated with sexual arousal showed neural activity in ventral CMS regions such
      as the venteromedial prefrontal cortex (VMPFC) and the perigenual anterior
      cingulate cortex (PACC), while self-related activity not associated with sexual
      arousal showed neural activity in the dorsomedial prefrontal cortex (DMPFC). Our
      study indicates that self-relatedness may be considered a crucial component in
      sexual arousal that is mediated by neural activity in ventral cortical midline
      structures.

PMID- 18633775
TI  - The role of the extrastriate body area in action perception.
AB  - Numerous cortical regions respond to aspects of the human form and its actions.
      What is the contribution of the extrastriate body area (EBA) to this network? In
      particular, is the EBA involved in constructing a dynamic representation of
      observed actions? We scanned 16 participants with fMRI while they viewed two
      kinds of stimulus sequences. In the coherent condition, static frames from a
      movie of a single, intransitive whole-body action were presented in the correct
      order. In the incoherent condition, a series of frames from multiple actions
      (involving one actor) were presented. ROI analyses showed that the EBA, unlike
      area MT + and the posterior superior temporal sulcus, responded more to the
      incoherent than to the coherent conditions. Whole brain analyses revealed
      increased activation to the coherent sequences in parietal and frontal regions
      that have been implicated in the observation and control of movement. We suggest
      that the EBA response adapts when succeeding images depict relatively similar
      postures (coherent condition) compared to relatively different postures
      (incoherent condition). We propose that the EBA plays a unique role in the
      perception of action, by representing the static structure, rather than dynamic
      aspects, of the human form.

PMID- 18633776
TI  - The visual analysis of emotional actions.
AB  - Is the visual analysis of human actions modulated by the emotional content of
      those actions? This question is motivated by a consideration of the
      neuroanatomical connections between visual and emotional areas. Specifically, the
      superior temporal sulcus (STS), known to play a critical role in the visual
      detection of action, is extensively interconnected with the amygdala, a center
      for emotion processing. To the extent that amygdala activity influences STS
      activity, one would expect to find systematic differences in the visual detection
      of emotional actions. A series of psychophysical studies tested this prediction.
      Experiment 1 identified point-light walker movies that convincingly depicted five
      different emotional states: happiness, sadness, neutral, anger, and fear. In
      Experiment 2, participants performed a walker detection task with these movies.
      Detection performance was systematically modulated by the emotional content of
      the gaits. Participants demonstrated the greatest visual sensitivity to angry
      walkers. The results of Experiment 3 suggest that local velocity cues to anger
      may account for high false alarm rates to the presence of angry gaits. These
      results support the hypothesis that the visual analysis of human action depends
      upon emotion processes.

PMID- 18633777
TI  - Language in shadow.
AB  - The recent finding that Broca's area, the motor center for speech, is activated
      during action observation lends support to the idea that human language may have
      evolved from neural substrates already involved in gesture recognition. Although
      fascinating, this hypothesis can be questioned because while observing actions of
      others we may evoke some internal, verbal description of the observed scene. Here
      we present fMRI evidence that the involvement of Broca's area during action
      observation is genuine. Observation of meaningful hand shadows resembling moving
      animals induces a bilateral activation of frontal language areas. This activation
      survives the subtraction of activation by semantically equivalent stimuli, as
      well as by meaningless hand movements. Our results demonstrate that Broca's area
      plays a role in interpreting actions of others. It might act as a motor-assembly
      system, which links and interprets motor sequences for both speech and hand
      gestures.

PMID- 18633778
TI  - The power of love on the human brain.
AB  - Romantic love has been the source for some of the greatest achievements of
      mankind throughout the ages. The recent localization of romantic love within
      subcortico-cortical reward, motivation and emotion systems in the human brain has
      suggested that love is a goal-directed drive with predictable facilitation
      effects on cognitive behavior, rather than a pure emotion. Here we show that the
      subliminal exposure of a beloved's name (romantic prime) during a lexical
      decision task dramatically improves performance in women in love (Experiment 1),
      as the subliminal presentation of a passion's descriptive noun does (Experiment
      2). The parallel between love and passion allows us to interpret these
      facilitation effects as corresponding to cognitive top-down processes within a
      motivation-enhanced neural network.

PMID- 18633779
TI  - Just seeing you makes me feel better: interpersonal enhancement of touch.
AB  - The human brain may contain "mirror systems" allowing mental simulation of the
      sensorimotor states of others. Most research has focused on interpersonal sharing
      of motor representations, with relatively little focus on sensation. Here we show
      that viewing the body of another person significantly enhances the spatial
      resolution of touch on the corresponding body part. Thirty subjects judged the
      orientation of gratings presented to the index finger tip, either when viewing
      their own hand, when viewing a neutral object presented in approximately the same
      location, or when viewing the undisguised hand of a third person standing behind
      them. Orientation discrimination was significantly more accurate when viewing
      one's own body compared to when viewing a neutral object. The same enhancement
      effect was found when viewing another's body. Performance when viewing one's own
      body did not differ significantly from performance when viewing the body of
      another person. This result suggests a purely sensory interpersonal sharing of
      body representations. It also suggests a specifically interpersonal modulation of
      primary sensory functions within the brain.

PMID- 18633780
TI  - The "reading the mind in films" task: complex emotion recognition in adults with
      and without autism spectrum conditions.
AB  - BACKGROUND: Individuals with autism spectrum conditions (ASC) have difficulties
      recognizing mental states in others. Most research has focused on recognition of
      basic emotions from faces and voices separately. This study reports the results
      of a new task, assessing recognition of complex emotions and mental states from
      social scenes taken from feature films. The film format arguably is more
      challenging and ecologically closer to real social situations. SAMPLE AND METHOD:
      A group of adults with ASC (n=22) were compared to a group of matched controls
      from the general population (n=22). Participants were tested individually.
      RESULTS: Overall, individuals with ASC performed significantly lower than
      controls. There was a positive correlation between verbal IQ and task scores.
      Using task scores, more than 90% of the participants were correctly allocated to
      their group. Item analysis showed that the errors individuals with ASC make when
      judging socioemotional information are subtle. CONCLUSIONS: This new test of
      complex emotion and mental state recognition reveals that adults with ASC have
      residual difficulties in this aspect of empathy. The use of language-based
      compensatory strategies for emotion recognition is discussed.

PMID- 18633781
TI  - A magnetoencephalography investigation of neural correlates for social exclusion
      and self-control.
AB  - Past research indicates that social exclusion leads to self-control failure. The
      present research examined the neural substrates of this effect. Participants were
      randomly assigned to either a social exclusion (n=15) or control (n=15)
      condition. Self-control was assessed by having participants solve 180 moderately
      difficult math problems while measuring how quickly they identified a supplied
      answer as correct or incorrect. Magnetoencephalography (MEG) was used to assess
      neural activity during this task. Socially excluded participants showed lesser
      activity in occipital and parietal cortex from 100-350 ms after the presentation
      of the math problems. When presented with the answers, socially excluded
      participants showed lesser activity in several regions, including occipital,
      parietal, and right prefrontal cortex from 100-300 ms post-stimulus. Furthermore,
      activation in the parietal and right prefrontal cortex mediated exclusion-control
      performance differences on math problems. The findings suggest that social
      exclusion interferes with the executive control of attention, and this effect is
      manifest in specific aspects of cognitive performance and brain function.

PMID- 18633782
TI  - Fetal testosterone and empathy: evidence from the empathy quotient (EQ) and the
      "reading the mind in the eyes" test.
AB  - Empathy involves an understanding of what others are thinking and feeling, and
      enables us to interact in the social world. According to the Empathizing
      Systemizing (E-S) theory, females on average have a stronger drive to empathize
      than males. This sex difference may in part reflect developmental differences in
      brain structure and function, which are themselves under the influence of fetal
      testosterone (fT). Previous studies have found that fT is inversely correlated
      with social behaviors such as eye contact in infancy, peer relationships in
      preschoolers, and mentalistic interpretation of animate motion. Male fetuses are
      exposed to higher levels of testosterone than are female fetuses. The present
      study investigates empathizing in children, as a function of amniotic measures of
      fT. One hundred ninety-three mothers of children (100 males, 93 females) aged 6-8
      years of age completed children's versions of the Empathy Quotient (EQ-C), and
      the children themselves were tested on "Reading the Mind in the Eyes" Task (Eyes
      C). All mothers had had amniocentesis during the 2nd trimester of pregnancy.
      There was a significant negative correlation between fT and scores on both
      measures. While empathy may be influenced by post-natal experience, these results
      suggest that pre-natal biology also plays an important role, mediated by androgen
      effects in the brain. These results also have implications for the causes of
      disabilities involving empathy, such as autism spectrum conditions, and may
      explain the increased rate of such conditions among males.

PMID- 18633783
TI  - The neuroscience of theory of mind.

PMID- 18633784
TI  - The ventromedial prefrontal cortex is involved in understanding affective but not
      cognitive theory of mind stories.
AB  - Lesion and neuroimaging studies have implicated the medial frontal lobes as
      playing an important role in our ability to predict other people's behavior by
      attributing to them mental states, such as beliefs, intention and emotion (termed
      "Theory of Mind"; ToM). However, recent studies have challenged these findings by
      highlighting the role of the temporal-parietal junction (TPJ) in ToM. In the
      present study, we tested the hypothesis that the ventromedial (VM) prefrontal
      cortex plays a unique role in affective ToM reasoning rather than a general role
      in ToM. We compared the performance of patients with lesions localized either in
      the VM, dorsolateral, TPJ, or superior parietal to healthy controls, with a
      battery of naturalistic affective and cognitive ToM stories (about false beliefs,
      false attribution, irony and lies). Patients with VM damage were impaired at
      providing appropriate mental state explanations for the affective ToM stories,
      compared to healthy controls and patients with posterior damage. In the VM group,
      performance in the affective ToM was significantly impaired as compared to
      cognitive ToM stories. Furthermore, in the VM group, ratings of levels of
      emotionality of each story suggested that levels of affective load correlated
      with number of errors in the stories, indicating that the more the emotional load
      involved in the story the greater the difficulty posed for the subjects in this
      group.

PMID- 18633785
TI  - Aphasia, language, and theory of mind.
AB  - We address the issue of the relation between language and theory of mind (ToM)
      reasoning involving the understanding of others' mental states. In particular, we
      focus on the evidence from people with aphasia and consider methodological issues
      concerning the nature of ToM tasks and test instructions. Research to date points
      to the independence of ToM from grammar in that studies of people with aphasia
      who have profound grammatical impairment retain ToM reasoning. By contrast,
      difficulties shown by young children and by adults with right hemisphere brain
      damage on certain ToM tasks often appear to involve the absence of a pragmatic
      awareness that precludes the expression of ToM reasoning.

PMID- 18633786
TI  - Getting a grip on other minds: mirror neurons, intention understanding, and
      cognitive empathy.
AB  - We have previously shown that a right inferior frontal mirror neuron area for
      grasping responds differently to observed grasping actions embedded in contexts
      that suggest different intentions, such as drinking and cleaning (Iacoboni,
      Molnar-Szakacs, Gallese, Buccino, Mazziotta, & Rizzolatti, 2005). Information
      about intentions, however, may be conveyed also by the grasping action itself:
      for instance, people typically drink by grasping the handle of a cup with a
      precision grip. In this fMRI experiment, subjects watched precision grips and
      whole-hand prehensions embedded in a drinking or an eating context. Indeed, in
      the right inferior frontal mirror neuron area there was higher activity for
      observed precision grips in the drinking context. Signal changes in the right
      inferior frontal mirror neuron area were also significantly correlated with
      scores on Empathic Concern subscale of the Interpersonal Reactivity Index, a
      measure of emotional empathy. These data suggest that human mirror neuron areas
      use both contextual and grasping type information to predict the intentions of
      others. They also suggest that mirror neuron activity is strongly linked to
      social competence.

PMID- 18633787
TI  - The effects of self-involvement on attention, arousal, and facial expression
      during social interaction with virtual others: a psychophysiological study.
AB  - Social neuroscience has shed light on the underpinnings of understanding other
      minds. The current study investigated the effect of self-involvement during
      social interaction on attention, arousal, and facial expression. Specifically, we
      sought to disentangle the effect of being personally addressed from the effect of
      decoding the meaning of another person's facial expression. To this end, eye
      movements, pupil size, and facial electromyographic (EMG) activity were recorded
      while participants observed virtual characters gazing at them or looking at
      someone else. In dynamic animations, the virtual characters then displayed either
      socially relevant facial expressions (similar to those used in everyday life
      situations to establish interpersonal contact) or arbitrary facial movements. The
      results show that attention allocation, as assessed by eye-tracking measurements,
      was specifically related to self-involvement regardless of the social meaning
      being conveyed. Arousal, as measured by pupil size, was primarily related to
      perceiving the virtual character's gender. In contrast, facial EMG activity was
      determined by the perception of socially relevant facial expressions irrespective
      of whom these were directed towards.

PMID- 18633788
TI  - Theory of mind broad and narrow: reasoning about social exchange engages ToM
      areas, precautionary reasoning does not.
AB  - Baron-Cohen (1995) proposed that the theory of mind (ToM) inference system
      evolved to promote strategic social interaction. Social exchange--a form of co
      operation for mutual benefit--involves strategic social interaction and requires
      ToM inferences about the contents of other individuals' mental states, especially
      their desires, goals, and intentions. There are behavioral and neuropsychological
      dissociations between reasoning about social exchange and reasoning about
      equivalent problems tapping other, more general content domains. It has therefore
      been proposed that social exchange behavior is regulated by social contract
      algorithms: a domain-specific inference system that is functionally specialized
      for reasoning about social exchange. We report an fMRI study using the Wason
      selection task that provides further support for this hypothesis. Precautionary
      rules share so many properties with social exchange rules--they are conditional,
      deontic, and involve subjective utilities--that most reasoning theories claim
      they are processed by the same neurocomputational machinery. Nevertheless,
      neuroimaging shows that reasoning about social exchange activates brain areas not
      activated by reasoning about precautionary rules, and vice versa. As predicted,
      neural correlates of ToM (anterior and posterior temporal cortex) were activated
      when subjects interpreted social exchange rules, but not precautionary rules
      (where ToM inferences are unnecessary). We argue that the interaction between ToM
      and social contract algorithms can be reciprocal: social contract algorithms
      requires ToM inferences, but their functional logic also allows ToM inferences to
      be made. By considering interactions between ToM in the narrower sense (belief
      desire reasoning) and all the social inference systems that create the logic of
      human social interaction--ones that enable as well as use inferences about the
      content of mental states--a broader conception of ToM may emerge: a computational
      model embodying a Theory of Human Nature (ToHN).

PMID- 18633789
TI  - The development and neural basis of referential gaze perception.
AB  - Infants are sensitive to the referential information conveyed by others' eye
      gaze, which could be one of the developmental foundations of theory of mind. To
      investigate the neural correlates of gaze-object relations, we recorded ERPs from
      adults and 9-month-old infants while they watched scenes containing gaze shifts
      either towards or away from the location of a preceding object. In adults, object
      incongruent gaze shifts elicited enhanced ERP amplitudes over the occipito
      temporal area (N330). In infants, a similar posterior ERP component (N290) was
      greater for object-incongruent gaze shifts, which suggests that by the age of 9
      months infants encode referential information of gaze in a similar way to adults.
      In addition, in infants we observed an early frontal ERP component (anterior
      N200), which showed higher amplitude in response to the perception of object
      congruent gaze shifts. This component may reflect fast-track processing of
      socially relevant information, such as the detection of communicative or
      informative situations, and could form a developmental foundation for attention
      sharing, social learning and theory of mind.

PMID- 18633790
TI  - Theory of mind in frontotemporal dementia.
AB  - Patients with frontotemporal dementia (FTD) exhibit marked changes in social and
      emotional functioning including lack of empathy, disinhibition, altered emotional
      reactivity, apathy and lack of insight. These changes are believed to be
      dependent on progressive frontal and temporal lobe degeneration. In this review,
      we discuss the nature of defective theory of mind and empathy in this group and
      relate it to regional dysfunction in the orbitofrontal and medial prefrontal
      cortex, based on evidence from several recent studies. The role of executive
      ability and co-existing emotional deficits are also considered.

PMID- 18633791
TI  - Thinking of mental and other representations: the roles of left and right temporo
      parietal junction.
AB  - Adopting new versions of the false belief and "false" photo vignettes used by
      Saxe & Kanwisher (2003) we were able to show activation in all five areas
      previously reported. Activations by added false sign and temporal change control
      vignettes in these areas showed that the right temporo-parietal junction (TPJ-R)
      is specifically associated with processing mental states like belief. In
      contrast, TPJ-L was also activated by false signs suggesting an association with
      processing perspective differences for mental and non-mental objects in line with
      work on visual perspective tasks. A similar, but less clearly interpretable
      pattern of activations was also found in the middle temporal gyrus, precuneus and
      in the MPFC. These results are discussed in relation to findings in normal
      development where false belief and false sign tasks associate more strongly with
      each other than does each of them with the "false" photo task.

PMID- 18633792
TI  - Eye tracking and fear recognition deficits in Turner syndrome.
AB  - Turner syndrome (TS) is a chromosomal disorder of X-monosomy in females. A
      minority have impaired social responsiveness, poor discrimination of facial
      emotions (especially fear), and abnormal amygdala-cortical connectivity. We
      tested the hypothesis that abnormal gaze fixation, especially with the eye region
      of faces, would be associated with these features, in a similar pattern to that
      seen in subjects with autism. Furthermore, since these features tend to be more
      striking in TS women whose X chromosome is maternal in origin, we also predicted
      that there may be a difference within the Turner's group according to parental
      origin of the single X. Adults with 45,X karyotype and age and IQ matched 46,XX
      women were recruited and tested. Facial fear recognition was significantly worse
      in 45,X females than controls, but there were no group differences according to
      parental origin of their single X chromosome. Subsequently, we tested 45,X and
      46,XX women using a remote eye-tracking device, as they viewed photographs of
      emotional human faces. Striking differences in scanpaths were found between the
      TS and controls, and within the TS group, but not according to parental origin of
      the X chromosome. These findings provide novel evidence for abnormal face
      processing in some women with TS, and indicate a potential neural mechanism
      underlying the difficulties in some key aspects of social cognition.

PMID- 18633793
TI  - Transgressors, victims, and cry babies: is basic moral judgment spared in autism?
AB  - Human social intelligence comprises a wide range of complex cognitive and
      affective processes that appear to be selectively impaired in autistic spectrum
      disorders. The study of these neuro-developmental disorders and the study of
      canonical social intelligence have advanced rapidly over the last twenty years by
      investigating the two together. Specifically, studies of autism have provided
      important insights into the nature of "theory of mind" abilities, their normal
      development and underlying neural systems. At the same time, the idea of impaired
      development of the neurocognitive mechanisms underlying "theory of mind" has shed
      new light on the nature of autistic disorders. This general approach is not
      restricted to the study of impairments but extends to mapping areas of social
      intelligence that are spared in autism. Here we investigate basic moral judgment
      and find that it appears to be substantially intact in children with autism who
      are severely impaired in "theory of mind". At the same time, we extend studies of
      moral reasoning in normal development by way of a new control task, the "cry
      baby" task. Cry baby scenarios, in which the distress of the victim is
      "unreasonable" or "unjustified," do not elicit moral condemnation from normally
      developing preschoolers or from children with autism. Judgments of moral
      transgressions in which the victim displays distress are therefore not likely the
      result of a simple automatic reaction to distress and more likely involve moral
      reasoning. Mapping the cognitive comorbidity patterns of disordered development
      must encompass both impairments and sparings because both are needed to make
      sense of the neural and genetic levels.

PMID- 18633794
TI  - Reading minds versus following rules: dissociating theory of mind and executive
      control in the brain.
AB  - The false belief task commonly used in the study of theory of mind (ToM) requires
      participants to select among competing responses and inhibit prepotent responses,
      giving rise to three possibilities: (1) the false belief tasks might require only
      executive function abilities and there may be no domain-specific component; (2)
      executive control might be necessary for the emergence of ToM in development but
      play no role in adult mental state inferences; and (3) executive control and
      domain-specific ToM abilities might both be implicated. We used fMRI in healthy
      adults to dissociate these possibilities. We found that non-overlapping brain
      regions were implicated selectively in response selection and belief attribution,
      that belief attribution tasks recruit brain regions associated with response
      selection as much as well-matched control tasks, and that regions associated with
      ToM (e.g., the right temporo-parietal junction) were implicated only in the
      belief attribution tasks. These results suggest that both domain-general and
      domain-specific cognitive resources are involved in adult ToM.

PMID- 18633795
TI  - Mid-frontal EEG alpha asymmetries predict individual differences in one aspect of
      theory of mind: mental state decoding.
AB  - Mental state decoding is the aspect of theory-of-mind (ToM) reasoning that
      requires individuals to make judgments about others' mental states based solely
      on immediately available information. We investigated whether individual
      differences in resting, task-independent frontal EEG alpha asymmetries predicted
      performance on the "Mind in the Eyes" (MIE) task, which is an established measure
      of mental state decoding skills. Group analyses showed that mental state decoding
      skills were stronger among those with right-lateralized frontal activation.
      Individual differences analyses showed that the degree of relative right mid
      frontal activation predicted performance on the task. These findings establish a
      neural correlate of individual differences in one aspect of ToM, and hypotheses
      about the precise mechanism involved are discussed.

PMID- 18633796
TI  - What's domain-specific about theory of mind?
AB  - Twenty years ago, Baron-Cohen and colleagues argued that autistic performance on
      false belief tests was explained by a deficit in metarepresentation. Subsequent
      research moved from the view that the mind has a domain-general capacity for
      metarepresentation to the view that the mind has a domain-specific mechanism for
      metarepresentation of mental states per se, i.e., the theory of mind mechanism
      (ToMM). We argue that 20 years of data collection in lesion patients and children
      with autism supports a more parsimonious view closer to that of the 1985 paper.
      Lower-level domain-specific mechanisms--e.g., tracking gaze, joint attention-
      interacting with higher-level domain-general mechanisms for metarepresentation,
      recursion, and executive function can account for observed patterns of deficits
      in both autism and neurological patients. The performance of children with autism
      or orbitofrontal patients on ToM tests can be explained more parsimoniously by
      their deficits in lower-level domain-specific mechanisms for processing social
      information. Without proper inputs, the intact capacity for metarepresentation by
      itself cannot make correct ToM inferences. Children with autism have no
      impairment in false photograph tests because their metarepresentational capacity
      is intact and they have no impairment in inputs required for such tests. TPJ
      patients have equivalent deficits on ToM and non-ToM metarepresentational tasks,
      consistent with a failure in domain-general processing. If deficits on ToM tasks
      can result from deficits in low-level input systems or in higher-level domain
      general capacities, postulating a separate ToM mechanism may have been an
      unnecessary theoretical move.

PMID- 18633797
TI  - Left hemisphere dominance in reading the sensory qualities of others' pain?
AB  - Seeing or imagining others in pain may activate both the sensory and affective
      components of the neural network (pain matrix) that is activated during the
      personal experience of pain. Transcranial magnetic stimulation (TMS), proved
      adept at highlighting the sensorimotor side of empathy for pain in studies where
      mere observation of needles penetrating body parts of a human model brought about
      a clear corticospinal motor inhibition. By using TMS, we investigated whether
      inferring the sensory properties of the pain of a model influenced the
      somatomotor system of an onlooker. Moreover, we tested the possible
      lateralization of the motor substrates underlying this reading process. We
      recorded motor-evoked potentials (MEPs) to left and right motor cortex
      stimulation during the observation of "flesh and bone" painful stimulations of
      right and left hands respectively. We found a significant reduction of onlookers'
      MEPs amplitudes specific to the muscle penetrated in the model. Subjective
      inferences about localization and intensity of the observed pain were associated
      with specific patterns of motor modulation with larger inhibitory effects
      following stimulation of the left motor cortex. Thus, results indicate that the
      mental simulation of the sensory qualities of others' pain may be lateralized to
      the left hemisphere.

PMID- 18633798
TI  - Intact first- and second-order false belief reasoning in a patient with severely
      impaired grammar.
AB  - The retention of first-order theory of mind (ToM) despite severe loss of grammar
      has been reported in two patients with left hemisphere brain damage (Varley &
      Siegal, 2000; Varley, Siegal, & Want, 2001). We report a third, and more
      detailed, case study. Patient PH shows significant general language impairment,
      and severe grammatical impairment similar to that reported in previous studies.
      In addition we were able to show that PH's impairment extends to grammatical
      constructions most closely related to ToM in studies of children (embedded
      complement clauses and relative clauses). Despite this, PH performed almost
      perfectly on first-order false belief tasks and on a novel nonverbal second-order
      false belief task. PH was also successful on a novel test of "ToM semantics" that
      required evaluation of the certainty implied by different mental state terms. The
      data strongly suggest that grammar is not a necessary source of structure for
      explicit ToM reasoning in adults, but do not rule out a critical role for "ToM
      semantics." In turn this suggests that the relationship observed between grammar
      and ToM in studies of children is the result of an exclusively developmental
      process.

PMID- 18633799
TI  - Impaired recognition of negative basic emotions in autism: a test of the amygdala
      theory.
AB  - Autism and Asperger Syndrome are autism spectrum conditions (ASC) characterized
      by deficits in understanding others' minds, an aspect of which involves
      recognizing emotional expressions. This is thought to be related to atypical
      function and structure of the amygdala, and performance by people with ASC on
      emotion recognition tasks resembles that seen in people with acquired amygdala
      damage. In general, emotion recognition findings in ASC have been inconsistent,
      which may reflect low numbers of participants, low numbers of stimuli and trials,
      heterogeneity of symptom severity within ASC groups, and ceiling effects on some
      tasks. The present study tested 39 male adults with ASC and 39 typical male
      controls on a task of basic emotion recognition from photographs, in two separate
      experiments. On a control face discrimination task the group with ASC were not
      impaired. People with ASC were less accurate on the emotion recognition task
      compared to controls, but only for the negative basic emotions. This is discussed
      in the light of similar findings from people with damage to the amygdala.

PMID- 18633800
TI  - Empathizing with basic emotions: common and discrete neural substrates.
AB  - Empathizing is a quantitative trait involving understanding another's mental
      state (including their emotion) and responding to this with an appropriate
      emotion. A reliable, behaviorally validated self-report questionnaire measure of
      this is the Empathy Quotient (EQ), which is continuously distributed across the
      general population. The "discrete emotions" model posits that each "basic"
      emotion has a relatively independent evolutionary antecedent and social
      communicative function and is subserved by a discrete neural system. In this
      study, we investigate if and how empathy influences the perception of basic
      emotions. Twenty-five volunteers (13 female, 12 male) selected across EQ space
      participated in a correlational design 3T fMRI study. The stimuli were presented
      in a box-car design, where 5 blocks (each containing 4 video clips of any one of
      happy, sad, angry, disgust or neutral expressions from different actors) and a
      low-level baseline were presented in pseudo-random order. Using an exploratory
      analysis, we found different brain regions correlated with EQ, depending on which
      emotion was being perceived. In particular, the ventral striatal response to
      happy faces correlated positively with EQ, while the ventral striatal response to
      sad faces was negatively correlated with EQ. The precuneus and lateral prefrontal
      cortical response to angry faces correlated positively with EQ. The response of
      the insula and the superior temporal gyrus cortex to disgust faces were
      negatively correlated with EQ. These results are discussed in the light of the
      postulated evolutionary function of each emotion. Using a hypothesis-driven
      conjunction analysis, we found that a region in the left dorsal inferior frontal
      gyrus/premotor cortex was positively correlated to the EQ across all four
      emotions. This region could therefore constitute a biomarker for trait empathy
      across emotions. We conclude that there are common regions underlying empathy
      across different emotions, and there are regions that show an emotion-specific
      correlation with empathy. This pattern of results is interpreted using a
      modification of Haxby et al.'s model of face perception.

PMID- 18633801
TI  - Co-operation with another player in a financially rewarded guessing game
      activates regions implicated in theory of mind.
AB  - Functional imaging studies have identified a network of brain regions associated
      with theory of mind (ToM); the attribution of mental states to other people.
      Similar regions have also been observed in studies where people play games that
      involve either competing or co-operating with another person. Such games are
      thought to place implicit demands on ToM processes. Co-operation with others has
      also been shown to elicit brain responses in areas associated with the processing
      of reward, suggesting that co-operation is an intrinsically rewarding process. In
      this study, we used a factorial design to assess the interaction between co
      operation and the availability of financial rewards in a guessing game. Twelve
      subjects were scanned with functional magnetic resonance imaging (fMRI) while
      they performed a guessing game with and without co-operation, and under both
      these conditions with and without financial reward. The main effect of co
      operation was associated with neural responses in theory of mind regions, while
      the main effect of financial reward was associated with neural responses in
      reward regions. Critically the response to reward in medial orbitofrontal cortex
      was significantly enhanced when subjects were co-operating. This suggests that
      rewards achieved through co-operation are more valuable than rewards achieved
      alone.

PMID- 18633802
TI  - Individual differences in theory of mind ability in middle childhood and links
      with verbal ability and autistic traits: a twin study.
AB  - Identifying the causal processes involved in theory of mind (ToM) development
      during childhood is an important goal for social neuroscience. This study aimed
      to investigate, for the first time, the extent to which individual differences in
      ToM are influenced by genes and environment in middle childhood, and to assess
      how ToM is linked to autistic-like behaviors and verbal ability. Over 600 9-year
      old twin pairs from a subsample of the Twins Early Development Study were
      assessed on an advanced test of ToM and on verbal ability. Parents, teachers, and
      the children themselves provided ratings of the twins' autistic traits (social
      impairments, communication impairments, and restricted repetitive behaviors and
      interests), using an abbreviated version of the Childhood Asperger Syndrome Test.
      Autistic traits, particularly communication impairments, significantly predicted
      ToM performance. Verbal ability showed the strongest phenotypic association with
      ToM. Twin model-fitting was employed to investigate the causes of this
      association. Much of the variation in ToM ability and in verbal ability was
      explained by environmental influences, with modest heritabilities for each, but
      their association was almost fully explained by shared genetic effects. The
      possible neural basis underlying this association is discussed.

PMID- 18633803
TI  - Spatial statistics of gaze fixations during dynamic face processing.
AB  - Social interaction involves the active visual perception of facial expressions
      and communicative gestures. This study examines the distribution of gaze
      fixations while watching videos of expressive talking faces. The knowledge-driven
      factors that influence the selective visual processing of facial information were
      examined by using the same set of stimuli, and assigning subjects to either a
      speech recognition task or an emotion judgment task. For half of the subjects
      assigned to each of the tasks, the intelligibility of the speech was manipulated
      by the addition of moderate masking noise. Both tasks and the intelligibility of
      the speech signal influenced the spatial distribution of gaze. Gaze was
      concentrated more on the eyes when emotion was being judged as compared to when
      words were being identified. When noise was added to the acoustic signal, gaze in
      both tasks was more centralized on the face. This shows that subject's gaze is
      sensitive to the distribution of information on the face, but can also be
      influenced by strategies aimed at maximizing the amount of visual information
      processed.

PMID- 18633804
TI  - The influence of self-regulatory focus on encoding of, and memory for, emotional
      words.
AB  - We investigated self-regulatory focus (Higgins, 1997, 1998) as one source of
      variation in encoding of, and memory for, emotional words. Participants wrote
      about their hopes and aspirations (promotion focus) or duties and obligations
      (prevention focus). In a subsequent incidental encoding task during functional
      magnetic resonance imaging (fMRI), participants evaluated emotional (positive and
      negative) and neutral words as either good or bad. A surprise memory test
      followed, outside the scanner. We observed a dissociation in posterior cingulate
      cortex (PCC), where activity during the evaluation task was greater when words
      were focus-consistent (positive for the promotion focus group, negative for the
      prevention focus group). Similarly, activity in a parahippocampal region was
      related to subsequent memory, but only for focus-consistent words. Given the role
      of the PCC in self-referential processing and episodic retrieval, and the
      parahippocampus in memory-related processing, these data suggest that regulatory
      focus influences which items are preferentially associated with self-referential
      information in memory. Such preferential processing may help explain why events
      are remembered differently by different individuals, which subsequently may
      influence interpersonal interactions.

PMID- 18633805
TI  - Unconscious processing of facial affect in children and adolescents.
AB  - In a previous study, with adults, we demonstrated that the amygdala and anterior
      cingulate gyrus are differentially responsive to happy and sad faces presented
      subliminally. Because the ability to perceive subtle facial signals communicating
      sadness is an important aspect of prosocial development, and is critical for
      empathic behavior, we examined this phenomenon from a developmental perspective
      using a backward masking paradigm. While undergoing functional magnetic resonance
      imaging (fMRI), 10 healthy adolescent children were presented with a series of
      happy and sad facial expressions, each lasting 20 ms and masked immediately by a
      neutral face to prevent conscious awareness of the affective expression. Relative
      to fixation baseline, masked sad faces activated the right amygdala, whereas
      masked happy faces failed to activate any of the regions of interest. Direct
      comparison between masked happy and sad faces revealed valence specific
      differences in the anterior cingulate gyrus. When the data were compared
      statistically to our previous sample of adults, the adolescent group showed
      significantly greater activity in the right amygdala relative to the adults
      during the masked sad condition. Groups also differed in several non-hypothesized
      regions. Development of unconscious perception from adolescence into adulthood
      appears to be accompanied by reduced activity within limbic affect processing
      systems, and perhaps increased involvement of other cortical and cerebellar
      systems.

PMID- 18633806
TI  - Exploring the brain basis of joint action: co-ordination of actions, goals and
      intentions.
AB  - Humans are frequently confronted with goal-directed tasks that can not be
      accomplished alone, or that benefit from co-operation with other agents. The
      relatively new field of social cognitive neuroscience seeks to characterize
      functional neuroanatomical systems either specifically or preferentially engaged
      during such joint-action tasks. Based on neuroimaging experiments conducted on
      critical components of joint action, the current paper outlines the functional
      network upon which joint action is hypothesized to be dependant. This network
      includes brain areas likely to be involved in interpersonal co-ordination at the
      action, goal, and intentional levels. Experiments focusing specifically on joint
      action situations similar to those encountered in real life are required to
      further specify this model.

PMID- 18633807
TI  - Cortical and subcortical mechanisms at the core of imitation.
AB  - Imitation is thought to require a perception-action matching process that
      utilizes the "mirror neuron" system, but other cognitive functions such as error
      detection may also be required for even simple imitation. We sought to explore
      the core neural substrate of imitation by examining the imitation of simple
      finger actions using fMRI. Participants observed one of two actions and were
      instructed to imitate the action they observed, or to perform the alternative non
      matching action. The contrast between imitation and non-matching actions was
      associated with activation in areas previously associated with imitation and
      "mirror neuron" functioning, including insula, intraparietal sulcus, dorsal
      premotor cortex, and superior temporal gyrus. Imitation was also specifically
      associated with activity in areas of prefrontal cortex, lateral orbitofrontal
      cortex (OFC), amygdala, red nucleus, thalamus, hippocampus, and substantia nigra.
      We suggest that lateral OFC responds to action-perception mismatch and other
      clusters reflect working memory, motor planning, associative learning, and visuo
      motor integration of goal-directed action. Although computational models have
      predicted integration of these functions to enable imitation, their specific
      brain bases have not previously been identified. Together they offer a
      potentially powerful means through which matching one's actions to those of
      others can lead to behavioral modification and development.

PMID- 18633808
TI  - Is it really my turn? An event-related fMRI study of task sharing.
AB  - Acting together with others is a fundamental human ability. This raises the
      possibility that we take others' actions into account whenever somebody acts
      around us. Event-related fMRI was used to identify brain regions responsive to
      changes in cognitive processing when one and the same go-nogo task is performed
      alone or together with a co-actor performing a complementary task. Reaction times
      showed that participants integrated the potential action of their co-actor in
      their own action planning. Increased activation in ventral premotor cortex was
      found when participants acted upon stimuli referring to their own action
      alternative, but only when their partner performed a complementary task. This
      suggests that knowing about the potential actions of a partner increases the
      relevance of stimuli referring to oneself. Acting in the presence of a co-actor
      was also associated with increased orbitofrontal activation, indicating that
      participants monitored their performance more closely to make sure it really was
      their turn. These results suggest that our default mode is to interact with
      others.

PMID- 18633809
TI  - Using brain-based measures to compose teams: how individual capabilities and team
      collaboration strategies jointly shape performance.
AB  - Advances in understanding neural processes open the possibility of using brain
      based measures to compose collaborative work teams. Neuroimaging studies have
      shown that individual differences in patterns of brain activity can predict
      differences in performance of specific tasks. We extended this finding by
      examining performance not simply by a single brain, but by pairs of brains. We
      used measures derived from brain-based studies to compose 100 two-person teams in
      which members' roles were either congruent or incongruent with their individual
      abilities. The assessed abilities are rooted in the visual system, which
      comprises independent "spatial" and "object" subsystems. The team task required
      one member to navigate through a virtual maze (a spatial task) and the other to
      remember "tag" repetitions of complex "greebles" (an object-properties task).
      Teams in which members' role assignments were congruent with their abilities
      performed better than incongruent teams and teams in which both members scored
      high on only one of the abilities. In addition, verbal collaboration enabled
      members of incongruent teams to overcome their compositional disadvantage but did
      not enhance the performance of congruent teams-and actually impaired performance
      in teams in which both members were adept in only one of the two necessary
      abilities. The findings show that knowledge about brain systems can not only be
      used to compose teams, but also provides insights into how teams can best
      perform.

PMID- 18633810
TI  - Processing of social emotion in patients with schizophrenia and substance use
      disorder: an fMRI study.
AB  - The lifetime prevalence of substance use disorders among schizophrenia patients
      is close to 50%. The negative consequences of substance abuse in schizophrenia
      are well documented, but the aetiology of this comorbid condition remains
      unknown. Mounting evidence suggests that dual-diagnosis patients have fewer
      negative symptoms and better social skills, compared to non-abusing patients. We
      hypothesized that schizophrenia patients with substance use disorder (SCZ-SUD)
      would display increased cerebral activations in response to socioemotional
      stimuli, relative to patients with no SUD (SCZ). Schizophrenia patients (DSM-IV
      criteria) were divided into two groups: patients with (n=12) and without (n=11)
      substance use (alcohol and/or cannabis). Using functional magnetic resonance
      imaging (fMRI), patients were scanned during passive viewing of an emotional film
      excerpt with social content. Loci of activation were identified in the right mPFC
      (BA 10) and the right supramarginal gyrus (BA 40) in SCZ-SUD patients, and in the
      left pons in SCZ patients. Relative to SCZ patients, increased loci of activation
      were found in the right superior parietal cortex (BA 7) and the left medial
      prefrontal cortex (BA 10) in SCZ-SUD patients, who reported higher subjective
      emotional experience on a self-report scale. To our knowledge, this is the first
      fMRI study to assess social emotions in dual-diagnosis schizophrenia. Our results
      suggest that socioemotional processing may be less impaired in dual diagnosis,
      which recruited brain regions seemingly involved in "social cognition." Further
      studies on the topic are warranted.

PMID- 18633811
TI  - Aging, self-referencing, and medial prefrontal cortex.
AB  - The lateral prefrontal cortex undergoes both structural and functional changes
      with healthy aging. In contrast, there is little structural change in the medial
      prefrontal cortex, but relatively little is known about the functional changes to
      this region with age. Using an event-related fMRI design, we investigated the
      response of medial prefrontal cortex during self-referencing in order to compare
      age groups on a task that young and elderly perform similarly and that is known
      to actively engage the region in young adults. Nineteen young (M age = 23) and
      seventeen elderly (M age = 72) judged whether adjectives described themselves,
      another person, or were presented in upper case. We assessed the overlap in
      activations between young and elderly for the self-reference effect (self vs.
      other person), and found that both groups engage medial prefrontal cortex and mid
      cingulate during self-referencing. The only cerebral differences between the
      groups in self versus other personality assessment were found in somatosensory
      and motor-related areas. In contrast, age-related modulations were found in the
      cerebral network recruited for emotional valence processing. Elderly (but not
      young) showed increased activity in the dorsal prefrontal cortex for positive
      relative to negative items, which could reflect an increase in controlled
      processing of positive information for elderly adults.

PMID- 18633812
TI  - Action during body perception: processing time affects self-other
      correspondences.
AB  - The accurate perception of other people and their postures is essential for
      functioning in a social world. Our own bodies organize information from others to
      help us respond appropriately by creating self-other mappings between bodies. In
      this study, we investigated mechanisms involved in the processing of self-other
      correspondences. Reed and Farah (1995) showed that a multimodal, articulated body
      representation containing the spatial relations among parts of the human body was
      accessed by both viewing another's body and moving one's own. Use of one part of
      the body representation facilitated the perception of homologous areas of other
      people's bodies, suggesting that inputs from both the self and other activated
      the shared body representation. Here we investigated whether this self-other
      correspondence produced rapid facilitation or required additional processing time
      to resolve competing inputs for a shared body representation. Using a modified
      Reed and Farah dual-task paradigm, we found that processing time influenced body
      position memory: an interaction between body-part moved and body-part attended
      revealed a relative facilitation effect at the 5 s ISI, but interference at the 2
      s ISI. Our results suggest that effective visual-motor integration from the self
      and other requires time to activate shared portions of the spatial body
      representation.

PMID- 18633813
TI  - Social neuroscience approaches to interpersonal sensitivity.
AB  - Interpersonal sensitivity refers to our ability to perceive and respond with care
      to the internal states (e.g., cognitive, affective, motivational) of another,
      understand the antecedents of those states, and predict the subsequent events
      that will result. This special issue brings together new research findings from
      empirical studies, including work with adults and children, genetics, functional
      neuroimaging, individual differences, and behavioral measures, which examine how
      we process and respond to information about our fellow individuals. By combining
      biological and psychological approaches, social neuroscience sheds new light on
      the complex and multi-faceted phenomenon of interpersonal sensitivity, including
      empathy. One should, however, be aware of the challenges and limits of such an
      approach.

PMID- 18633814
TI  - Interference effect of observed human movement on action is due to velocity
      profile of biological motion.
AB  - It has previously been shown that observing an action made by a human, but not by
      a robot, interferes with executed actions (Kilner, Paulignan, & Blakemore, 2003).
      Here, we investigated what aspect of human movement causes this interference
      effect. Subjects made arm movements while observing a video of either a human
      making an arm movement or a ball moving across the screen. Both human and ball
      videos contained either biological (minimum jerk) or non-biological (constant
      velocity) movements. The executed and observed arm movements were either
      congruent (same direction) or incongruent (tangential direction) with each other.
      The results showed that observed movements are processed differently according to
      whether they are made by a human or a ball. For the ball videos, both biological
      and non-biological incongruent movements interfered with executed arm movements.
      In contrast, for the human videos, the velocity profile of the movement was the
      critical factor: only incongruent, biological human movements interfered with
      executed arm movements. We propose that the interference effect could be due
      either to the information the brain has about different types of movement stimuli
      or to the impact of prior experience with different types of form and motion.

PMID- 18633815
TI  - Face to face: blocking facial mimicry can selectively impair recognition of
      emotional expressions.
AB  - People spontaneously mimic a variety of behaviors, including emotional facial
      expressions. Embodied cognition theories suggest that mimicry reflects internal
      simulation of perceived emotion in order to facilitate its understanding. If so,
      blocking facial mimicry should impair recognition of expressions, especially of
      emotions that are simulated using facial musculature. The current research tested
      this hypothesis using four expressions (happy, disgust, fear, and sad) and two
      mimicry-interfering manipulations (1) biting on a pen and (2) chewing gum, as
      well as two control conditions. Experiment 1 used electromyography over cheek,
      mouth, and nose regions. The bite manipulation consistently activated assessed
      muscles, whereas the chew manipulation activated muscles only intermittently.
      Further, expressing happiness generated most facial action. Experiment 2 found
      that the bite manipulation interfered most with recognition of happiness. These
      findings suggest that facial mimicry differentially contributes to recognition of
      specific facial expressions, thus allowing for more refined predictions from
      embodied cognition theories.

PMID- 18633816
TI  - Facial expressions: what the mirror neuron system can and cannot tell us.
AB  - Facial expressions contain both motor and emotional components. The inferior
      frontal gyrus (IFG) and posterior parietal cortex have been considered to compose
      a mirror neuron system (MNS) for the motor components of facial expressions,
      while the amygdala and insula may represent an "additional" MNS for emotional
      states. Together, these systems may contribute to our understanding of facial
      expressions. Here we further examine this possibility. In three separate event
      related fMRI experiment, subjects had to (1) observe (2) discriminate and (3)
      imitate facial expressions. Stimuli were dynamic neutral, happy, fearful and
      disgusted facial expressions, and in Experiments 1 and 2, an additional pattern
      motion condition. Importantly, during each experiment, subjects were unaware of
      the nature of the next experiments. Results demonstrate that even passive viewing
      of facial expressions activates a wide network of brain regions that were also
      involved in the execution of similar expressions, including the IFG/insula and
      the posterior parietal cortex. Only a subset of these regions responded more
      during the observation of facial than pattern motion (bilateral ventral IFG,
      bilateral STS/MTG, bilateral amygdala, SMA). While the viewing of facial
      expressions recruited similar brain regions in all three experiments, adding an
      active task (discrimination, imitation) augmented the magnitude of these
      activations. Brain activations reflected differences in observed facial
      expressions, with emotional expressions activating relatively more the
      insula/frontal operculum, and neutral ones (blowing up the cheeks) the
      somatosensory cortices (SII). Using movies, fear activated the amygdala and
      disgust the insula, but other emotions activated these structures to a similar
      degree.

PMID- 18633817
TI  - Imitation of in-group versus out-group members' facial expressions of anger: a
      test with a time perception task.
AB  - This research investigated the automatic imitation of facial expressions of anger
      by in-group and out-group members, using a temporal estimation task. Individuals
      typically overestimate duration represented by angry faces, probably due to
      increases in arousal (Droit-Volet, Brunot, & Niedenthal, 2004). Overestimation is
      not observed when imitation of the facial expressions is inhibited, suggesting
      that embodied simulation mediates the changes in arousal (Effron, Niedenthal,
      Gil, & Droit-Volet, 2006). This method thus provides an implicit measure of
      imitation and was used to test the hypothesis that individuals imitate in-group,
      but not out-group members' facial expressions of emotion. In separate studies
      Chinese and French Caucasian participants were presented with short (400 ms) and
      long (1600 ms) standard durations in a temporal bisection task. They then
      categorized standard and intermediate durations, represented by angry and neutral
      faces, in terms of similarity to the short and long standard durations. Half of
      the face stimuli were Chinese, and half Caucasian. Results revealed a bias in the
      temporal perception of emotion for the Caucasian participants when they were
      presented with Caucasian facial expressions and not Chinese ones. In contrast,
      this bias in time perception was observed when Chinese individuals imitated faces
      of both in- and out-group members. The results of the Chinese participants are
      interpreted in terms of familiarity with and motivations to understand the
      emotional expressions of members of a host culture.

PMID- 18633818
TI  - The neural substrates of cognitive empathy.
AB  - Neuroscientific research has consistently found that the perception of an
      affective state in another activates the observer's own neural substrates for the
      corresponding state, which is likely the neural mechanism for "true empathy."
      However, to date there has not been a brain-imaging investigation of so-called
      "cognitive empathy", whereby one "actively projects oneself into the shoes of
      another person," imagining someone's personal, emotional experience as if it were
      one's own. In order to investigate this process, we conducted a combined
      psychophysiology and PET and study in which participants imagined: (1) a personal
      experience of fear or anger from their own past; (2) an equivalent experience
      from another person as if it were happening to them; and (3) a nonemotional
      experience from their own past. When participants could relate to the scenario of
      the other, they produced patterns of psychophysiological and neuroimaging
      activation equivalent to those of personal emotional imagery, but when they could
      not relate to the other's story, differences emerged on all measures, e.g.,
      decreased psychophysiological responses and recruitment of a region between the
      inferior temporal and fusiform gyri. The substrates of cognitive empathy overlap
      with those of personal feeling states to the extent that one can relate to the
      state and situation of the other.

PMID- 18633820
TI  - Empathy and enduring depersonalization: the role of self-related processes.
AB  - Empathy has two key components: affective and cognitive. It relies on "embodied"
      processes such as the generation, representation and perception of feeling
      states. People diagnosed with Depersonalization Disorder (DPD) report
      disturbances in affective experience, such as emotional numbing, alongside
      aberrations in "body image" such as increased self-focus and feelings of
      "disembodiment". DPD therefore provides a test bed for the role of such self
      related processes in empathy. We tested 16 participants diagnosed with DPD and 48
      control volunteers on measures of cognitive and affective empathy. We used self
      report measures (EQ; Baron-Cohen & Wheelwright, 2004), an objective measure of
      cognitive empathy-the "Eyes" task (Baron-Cohen, Wheelwright, Hill, Raste, &
      Plumb, 2001), and a novel task tapping affective empathy, utilizing speech rate
      as an implicit measure of physiological arousal. We also measured participants'
      tendency to use mental representations that relate to the self during the
      affective empathy task. The DPD group showed intact performance on the cognitive
      empathy task. However, there was a disruption in the physiological component of
      affective empathy alongside a more pronounced reliance on mental representations
      of the self. These findings suggest affective empathy to be reliant on intact
      emotional experience in the observer. In addition, excessive self-focus may be
      detrimental to an empathic response.

PMID- 18633819
TI  - Different circuits for different pain: patterns of functional connectivity reveal
      distinct networks for processing pain in self and others.
AB  - The ability to empathize with the suffering of others is critical for maintaining
      relationships and engaging in prosocial behavior. Recently, a series of studies
      have demonstrated that while watching other people experience pain (other pain),
      participants engage the anterior insula (AI) and anterior cingulate cortex (ACC),
      brain regions involved in the direct experience of pain (self pain). Here we test
      the hypothesis that common activity in ACC and AI may reflect the operation of
      distinct but overlapping networks of regions that support perception of self or
      other pain. To address this possibility, we scanned participants using fMRI while
      they received noxious thermal stimulation (self pain) or watched short videos of
      other people sustaining painful injuries (other pain). We isolated overlapping
      regions for self and other pain in the ACC and AI and then used them as seed
      regions for two kinds of functional connectivity analyses. These analyses
      identified areas whose activity co-varied with ACC and AI activity during self or
      other pain either across time (intra-individual connectivity) or across
      participants (inter-individual connectivity). Both connectivity analyses
      identified clusters in the midbrain and periaqueductal gray with greater
      connectivity to the AI during self pain as opposed to other pain. The opposite
      pattern was found in the dorsal medial prefrontal cortex, that showed greater
      connectivity to the ACC and AI during other pain than during self pain using both
      types of analysis. Intra-individual connectivity analyses also revealed regions
      in the superior temporal sulcus, posterior cingulate, and precuneus that became
      more connected to ACC during other pain as compared to self pain. Together, these
      data demonstrated that regions showing similar activity during self and other
      pain may nonetheless be part of distinct functional networks. These networks
      could not have been detected in prior work that examined overlap between self and
      other pain in terms of average activity, but not connectivity.

PMID- 18633821
TI  - Only connect? Communication, identification, and autism.
AB  - In this paper, we elaborate a theoretical position and report an empirical study
      on a specific form of interpersonal engagement: the propensity to identify with
      the subjective orientation of another person. On the basis of a hypothesis that
      individuals with autism have a relative lack of this form of intersubjective
      connectedness (Hobson, 1993, 2002), we predicted that children and adolescents
      with autism would contrast with matched participants without autism (n=12 per
      group) in specific aspects of communication when someone requested them to "Get
      Pete to do this" and demonstrated actions in Pete's absence. As predicted, on
      blind ratings of videotapes of participants' communication, those with autism
      achieved lower scores on four indices of identification that were selected a
      priori: emotional engagement, sharing experience in joint attention,
      communication of style, and shifting in communicative role. The two groups were
      almost completely separate on a composite measure of identification. We consider
      the implications of these findings for typical and atypical development.

PMID- 18633822
TI  - The self as a moral agent: linking the neural bases of social agency and moral
      sensitivity.
AB  - The human brain is inherently able to understand the world in moral ways,
      endowing most of us with an intuitive sense of fairness, concern for others, and
      observance of cultural norms. We have argued that this moral sensitivity ability
      depends on a sophisticated integration of cognitive, emotional, and motivational
      mechanisms, which are modulated by individual experience in different cultural
      milieus. Different lines of investigation on agency and morality have pointed to
      overlapping neural systems. Therefore, understanding the relationships between
      morality and agency may provide key insights into the mechanisms underlying human
      behavior in several clinical and societal settings. We used functional MRI to
      investigate the contribution of agency and of specific moral emotions to brain
      activation using action scripts. Results showed that emotionally neutral agency
      recruited neural networks previously associated with agency, intentionality and
      moral cognition, encompassing ventral and subgenual sectors of the medial
      prefrontal cortex (PFC), insula, anterior temporal cortex and superior temporal
      sulcus (STS). Compared to emotionally neutral agency, different categories of
      moral emotions led to distinct activation patterns: (1) prosocial emotions
      (guilt, embarrassment, compassion) activated the anterior medial PFC and STS,
      with (2) empathic emotions (guilt and compassion) additionally recruiting the
      mesolimbic pathway; (3) other-critical emotions (disgust and indignation) were
      associated with activation of the amygdala-parahippocampal and fusiform areas.
      These findings indicate that agency related to norm-abiding social behaviors of
      emotionally neutral scripts share neural substrates both with the "default mode"
      of brain function and with the moral sensitivity network. Additional activation
      in specific components of this network is elicited by different classes of moral
      emotions, in agreement with recent integrative models of moral cognition and
      emotion.

PMID- 18633823
TI  - Simulation trouble.
AB  - I present arguments against both explicit and implicit versions of the simulation
      theory for intersubjective understanding. Logical, developmental, and
      phenomenological evidence counts against the concept of explicit simulation if
      this is to be understood as the pervasive or default way that we understand
      others. The concept of implicit (subpersonal) simulation, identified with neural
      resonance systems (mirror systems or shared representations), fails to be the
      kind of simulation required by simulation theory, because it fails to explain how
      neuronal processes meet constraints that involve instrumentality and pretense.
      Implicit simulation theory also fails to explain how I can attribute a mental or
      emotion state that is different from my own to another person. I also provide a
      brief indication of an alternative interpretation of neural resonance systems.

PMID- 18633825
TI  - Strategies of intention formation are reflected in continuous MEG activity.
AB  - Self-regulation of intention formation is pivotal for achieving behavior change.
      Fantasy realization theory (Oettingen, 2000) assumes that mentally contrasting a
      desired positive future with present negative reality turns high expectations of
      success into strong intentions to realize the desired future, while indulging in
      the positive future fails to do so. The present study tests the theory's process
      assumption that mental contrasting is a cognitively demanding, purposeful problem
      solving strategy involving working and episodic memory, whereas indulging is a
      mindless daydreaming strategy involving the free flow of thought, by
      investigating the neural correlates of the two strategies via continuous
      magnetoencephalographic (MEG) activity. We observed greater activity during
      mental contrasting (but not indulging) compared to resting in prefrontal,
      frontal, parietal, and temporal areas, indicating that mental contrasting
      involves strong intention formation, working memory, and episodic memory. In
      addition, heightened activity of occipital areas was observed during mental
      contrasting compared to resting and indulging, suggesting that mental
      contrasting, more than indulging and resting, entails purposefully creating
      mental images. Taken together, these findings indicate that mental contrasting is
      indeed a purposeful problem-solving strategy based on past performance history,
      whereas indulging is a purposeless daydreaming strategy that is oblivious to past
      experiences.

PMID- 18633826
TI  - Can simultaneously acquired electrodermal activity  improve accuracy of fMRI
      detection of deception?
AB  - Observation of changes in autonomic arousal was one of the first methodologies
      used to detect deception. Electrodermal activity (EDA) is a peripheral measure of
      autonomic arousal and one of the primary channels used in polygraph exams. In an
      attempt to develop a more central measure to identify lies, the use of functional
      magnetic resonance imaging (fMRI) to detect deception is being investigated. We
      wondered if adding EDA to our fMRI analysis would improve our diagnostic ability.
      For our approach, however, adding EDA did not improve the accuracy in a
      laboratory-based deception task. In testing for brain regions that replicated as
      correlates of EDA, we did find significant associations in right orbitofrontal
      and bilateral anterior cingulate regions. Further work is required to test
      whether EDA improves accuracy in other testing formats or with higher levels of
      jeopardy.

PMID- 18633827
TI  - Neural correlates of MDMA ("Ecstasy")-induced social interaction in rats.
AB  - The popular drug 3,4 methylenedioxymethamphetamine (MDMA, "Ecstasy", "the Love
      Drug") produces feelings of love and closeness in humans and induces analogous
      prosocial and antiaggressive effects in laboratory animals. Here we examined the
      specific brain regions that may be involved in these prosocial effects. Male
      Wistar rats were pretreated with a moderate dose of MDMA (5 mg/kg) or vehicle and
      then either kept alone in a familiar test chamber for 60 min (groups MDMA-ALONE
      and VEHICLE-ALONE) or allowed to engage in social interaction in the familiar
      test chamber with an unfamiliar same-sex conspecific for 60 min (groups MDMA
      SOCIAL and VEHICLE-SOCIAL). Rats in the MDMA-SOCIAL group showed much greater
      overall social interaction than rats in the VEHICLE-SOCIAL group, with
      microanalysis revealing increased general investigation of other rats but
      decreased anogenital sniffing. Analysis of neural activation across 39 brain
      regions using Fos immunohistochemistry showed the following results: (1) VEHICLE
      SOCIAL and VEHICLE-ALONE groups did not differ in Fos expression, indicating that
      a social context per se did not affect Fos expression, (2) MDMA-treated groups
      showed significantly increased Fos expression relative to VEHICLE treated groups
      in 30 brain regions, (3) the MDMA-SOCIAL group showed augmented Fos expression
      relative to the MDMA-ALONE group in six brain regions including the caudate
      putamen (medial), medial preoptic area, paraventricular thalamic nucleus, central
      amygdala, ventromedial hypothalamic nucleus, and the medial amygdala
      (posterodorsal), and (4) the MDMA-SOCIAL group (but not the MDMA-ALONE group)
      showed augmented Fos expression relative to the VEHICLE groups in the nucleus
      accumbens, ventral tegmental area and periaqueductal grey. These results indicate
      that a moderate dose of MDMA given in a social context causes considerably
      greater brain activation than the same dose given to solitary rats. This
      activation involves specific neural circuits that are known to regulate
      affiliative behavior, perhaps by modulating the incentive value of social
      stimuli. A possible role for the neuropeptide oxytocin in mediating the prosocial
      effects of MDMA is discussed.

PMID- 18633828
TI  - Action observation and execution: what is shared?
AB  - Performing an action and observing it activate the same internal representations
      of action. The representations are therefore shared between self and other
      (shared representations of action, SRA). But what exactly is shared? At what
      level within the hierarchical structure of the motor system do SRA occur?
      Understanding the content of SRA is important in order to decide what theoretical
      work SRA can perform. In this paper, we provide some conceptual clarification by
      raising three main questions: (i) are SRA semantic or pragmatic representations
      of action?; (ii) are SRA sensory or motor representations?; (iii) are SRA
      representations of the action as a global unit or as a set of elementary motor
      components? After outlining a model of the motor hierarchy, we conclude that the
      best candidate for SRA is intentions in action, defined as the motor plans of the
      dynamic sequence of movements. We shed new light on SRA by highlighting the
      causal efficacy of intentions in action. This in turn explains phenomena such as
      inhibition of imitation.

PMID- 18633830
TI  - Emotional states influence the neural processing of affective language.
AB  - The present study investigated whether emotional states influence the neural
      processing of language. Event-related potentials recorded the brain's response to
      positively and negatively valenced words (e.g., love vs. death) while
      participants were directly induced into positive and negative moods. ERP
      electrodes in frontal scalp regions of the brain distinguished positive and
      negative words around 400 ms poststimulus. The amplitude of this negative
      waveform showed a larger negativity for positive words compared to negative words
      in the frontal electrode region when participants were in a positive, but not
      negative, mood. These findings build on previous research by demonstrating that
      people process affective language differently when in positive and negative
      moods, and lend support to recent views that emotion and cognition interact
      during language comprehension.

PMID- 18633829
TI  - Atypical frontal-posterior synchronization of Theory of Mind regions in autism
      during mental state attribution.
AB  - This study used fMRI to investigate the functioning of the Theory of Mind (ToM)
      cortical network in autism during the viewing of animations that in some
      conditions entailed the attribution of a mental state to animated geometric
      figures. At the cortical level, mentalizing (attribution of metal states) is
      underpinned by the coordination and integration of the components of the ToM
      network, which include the medial frontal gyrus, the anterior paracingulate, and
      the right temporoparietal junction. The pivotal new finding was a functional
      underconnectivity (a lower degree of synchronization) in autism, especially in
      the connections between frontal and posterior areas during the attribution of
      mental states. In addition, the frontal ToM regions activated less in
      participants with autism relative to control participants. In the autism group,
      an independent psychometric assessment of ToM ability and the activation in the
      right temporoparietal junction were reliably correlated. The results together
      provide new evidence for the biological basis of atypical processing of ToM in
      autism, implicating the underconnectivity between frontal regions and more
      posterior areas.

PMID- 18633831
TI  - Functional magnetic resonance imaging of temporally distinct responses to
      emotional facial expressions.
AB  - Understanding the temporal dynamics of brain function contributes to models of
      learning and memory as well as the processing of emotions and habituation. In
      this article, we present a novel analysis technique to investigate spatiotemporal
      patterns of activation in response to blocked presentations of emotional stimuli.
      We modeled three temporal response functions (TRFs), which were maximally
      sensitive to the onset, early or sustained temporal component of a given block
      type. This analysis technique was applied to a data set of 29 subjects who
      underwent functional magnetic resonance imaging while responding to fearful,
      happy, and sad facial expressions. We identified brain regions that uniquely fit
      each of the three TRFs for each emotional condition and compared the results to
      the standard approach, which was based on the canonical hemodynamic response
      function. We found that voxels within the precuneus fit the onset TRF but did not
      fit the early or the sustained TRF in all the emotional conditions. On the other
      hand, voxels within the amygdala fit the sustained TRF, but not the onset or
      early TRF, during presentation of fearful stimuli, suggesting a spatiotemporal
      dissociation between these structures. This technique provides researchers with
      an additional tool in order to investigate the temporal dynamics of neural
      circuits.

PMID- 18633832
TI  - Detection of deception using fMRI: better than chance, but well below perfection.
AB  - Functional brain imaging has been considered a new and better technique for the
      detection of deception. The reasoning is that there is a neural locus or circuit
      for lying that is sensitive, specific, generalizable across individuals and
      measurement contexts, and robust to countermeasures. To determine the extent to
      which the group results predicted lying at the level of the individual, we
      reanalyzed data on 14 participants from a study that had previously identified
      regions involved in lying (thus satisfying the criterion for sensitivity). We
      assessed the efficacy of functionally determined brain regions based on the lie
      truth contrast for N-1 participants to detect deception in the Nth individual.
      Results showed that no region could be used to correctly detect deception across
      all individuals. The best results were obtained for medial prefrontal cortex
      (mPFC), correctly identifying 71% of participants as lying with no false alarms.
      Lowering the threshold for a response increased hits and false alarms. The
      results suggest that although brain imaging is a more direct index of cognition
      than the traditional polygraph, it is subject to many of the same caveats and
      thus neuroimaging does not appear to reveal processes that are necessarily unique
      to deception.

PMID- 18633833
TI  - Action co-representation: the joint SNARC effect.
AB  - Traditionally, communication has been defined as the intentional exchange of
      symbolic information between individuals. In contrast, the mirror system provides
      a basis for nonsymbolic and nonintentional information exchange between
      individuals. We believe that understanding the role of the mirror system in joint
      action has the potential to serve as a bridge between these two domains. The
      present study investigates one crucial component of joint action: the ability to
      represent others' potential actions in the same way as one's own in the absence
      of perceptual evidence. In two experiments a joint spatial numerical association
      of response codes (SNARC) effect is demonstrated, providing further evidence that
      individuals form functionally equivalent representations of their own and others'
      potential actions. It is shown that numerical (symbolic) stimuli that are mapped
      onto a spatially arranged internal representation (a mental number line) can
      activate a co-represented action in the same way as spatial stimuli. This
      generalizes previous results on co-representation.We discuss the role of the
      mirror system in co-representation as a basis for shared intentionality and
      communication.

PMID- 18633834
TI  - Listening to humans walking together activates the  social brain circuitry.
AB  - Human footsteps carry a vast amount of social information, which is often
      unconsciously noted. Using functional magnetic resonance imaging, we analyzed
      brain networks activated by footstep sounds of one or two persons walking.
      Listening to two persons walking together activated brain areas previously
      associated with affective states and social interaction, such as the subcallosal
      gyrus bilaterally, the right temporal pole, and the right amygdala. These areas
      seem to be involved in the analysis of persons' identity and complex social
      stimuli on the basis of auditory cues. Single footsteps activated only the
      biological motion area in the posterior STS region. Thus, hearing two persons
      walking together involved a more widespread brain network than did hearing
      footsteps from a single person.

PMID- 18633835
TI  - Towards clinical trials of lie detection with fMRI.
AB  - Recent reports of successful fMRI-based discrimination between lie and truth in
      single subjects raised the interest of prospective users and a public concern
      about the potential scope of this technology. The increased scrutiny highlighted
      the lack of controlled "real life", i.e. prospective clinical trials of this
      technology that conform to the common standards of medical device development.
      The ethics of conducting such trials given the paucity of data on fMRI-based lie
      detection has also been questioned. To probe the potential issues of translating
      the laboratory research into practice, we conducted a case study in which we
      adapted the standard Guilty Knowledge Test (GKT), a well-established model of
      producing deception, to the common scenario of lying on a resume. The task
      consisted of questions about pertinent items on the subject's resume, three of
      which could be independently verified as truth (KNOWN) and three that could not
      be verified and were thus termed UNKNOWN. The subject had an incentive to lie on
      all UNKNOWN items, and on debriefing confirmed that he had done so. Data was
      preprocessed, masked with a priori regions of interest, thresholded, and
      qualitatively evaluated for consistency with the previously reported prefronto
      parietal Lie > Truth pattern. Deceptive responses to two out of the three UNKNOWN
      items were associated with the predicted prefronto-parietal fMRI pattern. In the
      third UNKNOWN this pattern was absent, and instead, increased limbic (amygdala
      and hippocampus) response was observed. Based on published prefronto-parietal Lie
      response pattern, only the first two items could be categorized as Lie. If
      confirmed, this demonstration of amygdala and hippocampus activation in a Lie >
      Truth contrast illustrates the need to integrate the limbic system and its
      emotional and cognitive correlates into the existing model of deception. Our
      experiment suggests an approach to a naturalistic scenario and the research
      questions that need to be answered in order to set the stage for prospective
      clinical trials of fMRI-based lie detection.

PMID- 18633836
TI  - Thirty-site P300 scalp distribution, amplitude variance across sites, and
      amplitude in detection of deceptive concealment of multiple guilty items.
AB  - Previous tests of P300 in deception detection have focused mainly on amplitude
      analysis. Since countermeasures for such tests have been reported, we looked here
      at other possible variables as deception indices: P300 scalp distribution and
      amplitude variance, both across 30 sites. We were also concerned, for the first
      time, in testing for recognition of more than one guilty item in a mock crime
      scenario. There were three groups: (1) two-probe group, two of six items were
      guilty knowledge (GK) items; (2) three-probe group, three of six items were GK
      items; (3) control group, zero of six items were GK items. In group analyses, in
      the two-probe group, P300s for lies were significantly greater than P300s for
      truthful responses. There were significant interactions of condition (Lie vs
      Truth) by site, suggesting different scalp profiles for deceptive versus truthful
      responding. Amplitude variance across sites was also greater in Lie than in Truth
      blocks. These results did not obtain in the three-probe and control groups. In
      terms of amplitude variances in probe conditions across groups, two-probe group
      was larger than three-probe and control groups. Regarding individual diagnostics,
      the variance method yielded a greater-than-chance detection rate of 71% versus
      28% false positives. Regarding amplitude at multiple nonfrontal sites, 71% of
      guilty subjects were detected versus 14% false positives. Grier's (1971) A'
      indices of various test discrimination efficiencies varied from .76 to .87.
      Results of the present study suggested further investigation of the variance
      method as a diagnostic tool for lie detection.

PMID- 18633837
TI  - Second to fourth digit ratios, sex differences, and behavior in Chinese men and
      women.
AB  - The ratio of the length of the second and fourth digits (2D:4D ratio) is
      consistently smaller in men than in women. Additionally, within each sex, smaller
      digit ratios may be associated with higher testosterone levels and/or more
      masculine attitudes and behaviors, although these findings are less consistent.
      We assessed 2D:4D ratios, together with measures of masculine attitudes and
      behaviors, in an ethnically homogeneous population of 118 men and 103 women, aged
      21-38, all heterosexual and right-handed, in Beijing, China. In men, we also
      measured salivary testosterone levels. As predicted, men displayed significantly
      smaller 2D:4D ratios than women (pB.0001 in both hands). Within each sex,
      however, 2D:4D ratios, measures of masculine characteristics, and salivary
      testosterone showed no significant associations with one another. These latter
      null findings may partially reflect cultural differences in definitions of
      "masculinity".

PMID- 18633838
TI  - Female stimuli trigger gene expression in male pigeons.
AB  - The immediate early gene zenk encodes transcriptional regulators and is believed
      to be one of the first steps in the formation of long-term memories associated
      with a given stimulus. In this study, we investigated the expression of ZENK
      protein product in brain regions that are likely involved in the processing of
      social stimuli, such as a potential mate. Male pigeons (Columba livia) were
      exposed to one of the following: (1) a live female pigeon, (2) a video playback
      of a female pigeon, (3) a video playback of a female cockatoo, or (4) an empty
      stimulus chamber. The brains were then processed immunohistochemically using an
      antibody against ZENK protein. When the stimulus was a live pigeon compared to
      all other stimuli, there were more numerous and more darkly-stained ZENK-positive
      cells in three "association" regions of the telencephalon: the hyperpallium
      apicale, the lateral portion of the intermediate nidopallium, and the medial
      nidopallium. There were no significant differences among the video-playback
      stimuli. The results suggest that the level of ZENK expression in these
      "association" regions was influenced not only by the visual presence of a
      potential mate, but by the presence of non-visual signals, the quality of the
      image, and the real-time interaction with the stimulus.

PMID- 18633839
TI  - Disturbances of self-other distinction after stimulation of the extrastriate body
      area in the human brain.
AB  - In a recent experiment with functional magnetic-resonance imaging, we found that
      brain activity in the extrastriate body area (EBA) distinguished between observed
      self- and other-generated movements, being significantly higher during
      observation of someone else's movement. Here, we investigated further the role of
      EBA in self-other distinctions using low-frequency repetitive transcranial
      magnetic stimulation (rTMS). As compared with rTMS applied over a control site,
      rTMS applied over the EBA increased reaction times, without affecting accuracy,
      for the detection of other-generated movements. Performance on a control motion
      direction detection task was unaffected. These findings provide additional
      evidence for the role of the EBA in processing information necessary for
      identifying ourselves as agents of self-generated movements.

PMID- 18633840
TI  - Social state representation in prefrontal cortex.
AB  - One of the cardinal mental faculties of humans and other primates is social brain
      function, the collective name assigned to the distributed system of social
      cognitive processes that orchestrate our sophisticated adaptive social behavior.
      These must include processes for recognizing current social context and
      maintaining an internal representation of the current social state as a reference
      for decision-making. But how and where the brain processes such social-state
      information is unknown. To home in on the neural substrates of social-state
      representation, the activity of 196 prefrontal (PFC) neurons was recorded from
      two monkeys simultaneously during a food-grab task under varying social
      conditions. Of PFC neurons, 39% showed activity modulation during movement-free
      periods and seemed to be representing current social state. The direction of
      modulation was opposite between the dominant and submissive monkeys: During
      social engagement, PFC activity increased in the dominant monkey and was
      suppressed in the submissive monkey. The modulation was consistently observed in
      additional PFC neurons (27/72) in additional pairings with two other monkeys.
      Notably, PFC activity in one formerly submissive monkey switched to dominant
      modulation mode when he was paired with a new monkey of lower social status.
      These findings suggest that PFC, as part of a larger social brain network,
      maintains a multistate classification of social context for use as a behavioral
      reference for social decision-making.

PMID- 18633841
TI  - Perceived similarity and neural mirroring: evidence from vicarious error
      processing.
AB  - This study examined the effects of interpersonal similarity on vicarious error
      processing. We predicted that high similarity between self and other would
      predict increased neural responsiveness to the other's errors, based on the
      assumption that experience is more strongly shared when it involves similar
      others. Participants observed a confederate performing a flanker task while event
      related brain potentials were recorded from the observer. Physiological data
      revealed two error-related potentials, the observational error-related negativity
      (oERN) and positivity (oPe). Self-reports of perceived similarity toward the
      confederate predicted both components. Participants reporting higher
      interpersonal similarity showed a larger oPe response to the other's errors,
      suggesting increased salience of errors committed by similar others.
      Unexpectedly, higher similarity also predicted a decreased oERN response.
      Divergent results for oERN and oPe may reflect the different functional roles of
      the two components. Together the results demonstrate that vicarious error
      monitoring is sensitive to social factors.

PMID- 18633842
TI  - Limitations to the detection of deception: true and false recollections are
      poorly distinguished using an event-related potential procedure.
AB  - The utility of using indices of neural function to identify deception relies on
      finding highly reliable and valid approaches that adequately identify the guilty
      and exonerate the innocent. A class of approaches, based on the guilty knowledge
      technique (GKT), assume that guilty individuals will recognize specific crime
      relevant details, whereas innocent individuals will not. Memory distortions,
      however, may limit the accuracy of such procedures. To investigate these limits,
      two studies were conducted to examine whether brain electrical activity could
      differentiate true from false recollections elicited by the Deese-Roediger
      McDermott (DRM) paradigm. The design of each study maximized the opportunity of
      finding electrocortical differences between true and false recognition. Each
      study found very high rates of false recognition, with little evidence that brain
      electrical activity could differentiate true from false memories. Results
      suggested that under certain conditions both true and false recollections can
      produce a pattern of brain activity indicative of recognition.

PMID- 18633843
TI  - Perceived causality influences brain activity evoked by biological motion.
AB  - Using functional magnetic resonance imaging (fMRI), we investigated brain
      activity in an observer who watched the hand and arm motions of an individual
      when that individual was, or was not, the cause of the motion. Subjects viewed a
      realistic animated 3D character who sat at a table containing four pistons. On
      Intended Motion trials, the character raised his hand and arm upwards. On
      Unintended Motion trials, the piston under one of the character's hands pushed
      the hand and arm upward with the same motion. Finally, during Non-Biological
      Motion control trials, a piston pushed a coffee mug upward in the same smooth
      motion. Hand and arm motions, regardless of intention, evoked significantly more
      activity than control trials in a bilateral region that extended ventrally from
      the posterior superior temporal sulcus (pSTS) region and which was more spatially
      extensive in the right hemisphere. The left pSTS near the temporal-parietal
      junction, robustly differentiated between the Intended Motion and Unintended
      Motion conditions. Here, strong activity was observed for Intended Motion trials,
      while Unintended Motion trials evoked similar activity as the coffee mug trials.
      Our results demonstrate a strong hemispheric bias in the role of the pSTS in the
      perception of causality of biological motion.

PMID- 18633844
TI  - Ideomotor action in cooperative and competitive settings.
AB  - Ideomotor movements may arise in observers while they watch other people's
      actions. Previous studies have shown that ideomotor movements are guided by both
      perceptual and intentional characteristics of the actions being observed
      (perceptual induction and intentional induction, respectively; cf. Knuf,
      Aschersleben, & Prinz, 2001; de Maeght & Prinz, 2004). In the present study we
      explore the functional basis of intentional induction. More specifically we raise
      the issue of whose intentions count for intentional induction: observers' own
      intentions or observees' (implied) intentions? We studied ideomotor movements in
      a cooperative and a competitive task setting. In the cooperative setting
      observers' and observees' intentions were identical, but in the competitive
      setting they were different. Results indicate that ideomotor movements are guided
      by the observers' own intentions, not the observees' implied intentions. Our
      findings suggest that, though observers understand the intentions of others,
      their ideomotor movements are guided by their own intentions, expressing what
      they themselves wish to see the other is doing.

PMID- 18633845
TI  - What's in a smile? Neural correlates of facial embodiment during social
      interaction.
AB  - Previous investigations have shown that the perception of socially relevant
      facial expressions, indicating someone else's intention to communicate (e.g.,
      smiling), correlate with increased activity in zygomaticus major muscle
      regardless of whether the facial expressions seen are directed towards the human
      observer or toward someone else (Mojzisch et al., 2006). These spontaneous,
      involuntary reactions have been described as facial mimicry and seem to be of
      considerable importance for successful interpersonal communication. We
      investigated whether specific neural substrates underlie these responses by
      performing a finite impulse response (FIR) analysis of an experiment using
      functional magnetic resonance imaging (fMRI) to investigate the perception of
      socially relevant facial expressions (Schilbach et al., 2006). This analysis
      demonstrates that differential neural activity can be detected relative to the
      FIR time window in which facial mimicry occurs. The neural network found includes
      but extends beyond classical motor regions (face motor area) recruiting brain
      regions known to be involved in social cognition. This network is proposed to
      subserve the integration of emotional and action-related processes as part of a
      pre-reflective, embodied reaction to the perception of socially relevant facial
      expressions as well as a reflective representation of self and other.

PMID- 18633846
TI  - Observing social interactions: the effect of gaze.
AB  - Our social abilities depend on specialized brain systems that allow us to perform
      crucial operations such as interpreting the actions of others. This functional
      magnetic resonance imaging (fMRI) study investigated whether human brain activity
      evoked by the observation of social interactions is modulated by gaze. During
      scanning participants observed social or individual actions performed by agents
      whose gaze could be either available or masked. Results demonstrated that the
      observation of social interactions evoked activity within a dorsal sector of the
      medial prefrontal cortex (MPFC), an area classically involved in social
      cognition. Importantly, activity within this area was modulated by whether the
      gaze of the agents performing the observed action was or was not available. The
      implications of these findings for a role played by the dorsal medial prefrontal
      cortex (dMPFC) in terms of inferential processes concerned with social
      interactions are considered.

PMID- 18633847
TI  - Rhesus monkeys' understanding of actions and goals.
AB  - A forced-choice social foraging method was used to explore how free-ranging
      rhesus monkeys make inferences about other individuals' goals and intentions.
      Subjects saw an experimenter perform an action towards one of two potential food
      sources, then were allowed to approach and choose one of those sources. Results
      showed that subjects selectively picked the food source targeted by the
      experimenter's action only when the action was within the rhesus' motor
      repertoire. Further studies explored the extent to which rhesus attend to the
      details of the goal as well as the means by which the goal was obtained, with
      results paralleling those obtained from cellular recordings of macaque mirror
      neurons. Monkeys' pattern of success and failure supports the hypothesis that
      motor areas play a functionally significant role in event parsing and action
      understanding.

PMID- 18633848
TI  - Extracting variant and invariant information from faces: the neural substrates of
      gaze detection and sex categorization.
AB  - Guided by influential models of face processing, efforts have been expended to
      uncover the neural substrates subserving the many facets of face perception.
      Extending this work, the present study used functional brain imaging (fMRI) to
      explore the relationship between the operations supporting the explicit
      extraction of sex and gaze-related information from faces. The brain imaging data
      showed the right superior temporal sulcus to be preferentially involved during
      assessments of gaze direction and a region of the left fusiform gyrus to be
      involved during sex categorization. These results provide support for the
      distributed face-processing model advanced by Haxby and colleagues (2000).

PMID- 18633849
TI  - Structural neural correlates of impairments in social cognition in first episode
      psychosis.
AB  - Several studies have demonstrated that patients with schizophrenia show
      impairments in social cognition and current evidence indicate that this deficit
      is associated with abnormal activity in specific brain regions. In addition to
      functional imaging studies, we believe that the identification of structural
      correlates of social cognitive processes may help to better understand the neural
      underpinnings of these specific skills. The main objective of this study was to
      investigate the relationship between gray matter density and social cognitive
      deficits in first episode of schizophrenia spectrum psychosis, using a
      comprehensive assessment that we previously demonstrated to be a highly sensitive
      measure of social cognitive deficits in this population. Thirty-eight patients
      with a first episode of psychosis participated in this study, and the Four Factor
      Test of Social Intelligence was used as a measure of social cognition. Social
      cognitive impairments in first episode psychosis were significantly correlated
      with reduced gray-matter density in the left middle frontal gyrus other regions
      within the mirror neuron system network (MSN), namely the right supplementary
      motor cortex, the left superior temporal gyrus and the left inferior parietal
      lobule. We concluded that structural abnormalities within the MSN may account for
      the social cognitive deficits present in some psychiatric disorders, such as
      schizophrenia.

PMID- 18633850
TI  - Integrating physical and social cues when forming face preferences: differences
      among low and high-anxiety individuals.
AB  - This study investigated individual differences in the integration of social
      (i.e., direction of social interest) and physical (i.e., apparent health) cues in
      a face preference test. While low-anxiety individuals demonstrated preferences
      for social engagement from healthy-looking faces, but not from unhealthy-looking
      faces, high-anxiety individuals preferred social engagement from both healthy and
      unhealthy individuals. Importantly, anxious individuals were not simply less
      discriminating in their face preferences generally: anxiety levels were
      positively related to the strength of overall preferences for positive social
      interest. Collectively, our findings show that perceptions of gaze and expression
      can be modulated by aspects of facial appearance and that systematic variation
      among individuals exists in the extent to which this modulation occurs.
      Furthermore, since previous studies have demonstrated hypersensitive amygdala
      responses among anxious individuals when viewing faces, our findings suggest that
      the amygdala may play an important role in determining how different facial cues
      are integrated in person perception.

PMID- 18633851
TI  - Neural consequences of religious belief on self-referential processing.
AB  - Christianity strongly encourages its believers to surrender to God and to judge
      the self from God's perspective. We used functional MRI to assess whether this
      religious belief is associated with neural correlates of self-referential
      processing distinct from that of non-religious people. Non-religious and
      Christian participants were scanned while performing tasks of personal-trait
      judgments regarding the self or public persons. We found that, while self
      judgment was linked to better memory of traits related to the self than to
      others, self-referential processing induced increased activity in the ventral
      medial prefrontal cortex (MPFC) for non-religious participants but in the dorsal
      MPFC for Christian participants. In addition, the dorsal MPFC activity was
      positively correlated with the rating scores of the importance of Jesus' judgment
      in subjective evaluation of a person's personality. Because the ventral and
      dorsal MPFC are respectively engaged in representation of stimulus self-relevance
      and evaluation of self-referential stimuli, our findings suggest that Christian
      beliefs result in weakened neural coding of stimulus self-relatedness but
      enhanced neural activity underlying evaluative processes applied to self
      referential stimuli.

PMID- 18633852
TI  - Levels of emotional awareness and autism: an fMRI study.
AB  - Autism is associated with an inability to identify and distinguish one's own
      feelings. We assessed this inability using alexithymia and empathy
      questionnaires, and used fMRI to investigate brain activity while introspecting
      on emotion. Individuals with high functioning autism/Asperger syndrome (HFA/AS)
      were compared with matched controls. Participants rated stimuli from the
      International Affective Picture System twice, once according to the degree of
      un/pleasantness that the pictures induced, and once according to their color
      balance. The groups differed significantly on both alexithymia and empathy
      questionnaires. Alexithymia and lack of empathy were correlated, indicating a
      link between understanding one's own and others' emotions. For both groups a
      strong relationship between questionnaire scores and brain activity was found in
      the anterior insula (AI), when participants were required to assess their
      feelings to unpleasant pictures. Regardless of self-reported degree of emotional
      awareness, individuals with HFA/AS differed from controls when required to
      introspect on their feelings by showing reduced activation in self
      reflection/mentalizing regions. Thus, we conclude that difficulties in emotional
      awareness are related to hypoactivity in AI in both individuals with HFA/AS and
      controls, and that the particular difficulties in emotional awareness in
      individuals with HFA/AS are not related to their impairments in self
      reflection/mentalizing.

PMID- 18633853
TI  - Asymmetrical frontal ERPs, emotion, and behavioral approach/inhibition
      sensitivity.
AB  - The present study sought to extend past research on frontal brain asymmetry and
      individual differences by examining relationships of individual differences in
      behavioral inhibition/approach system (BIS/BAS) sensitivity with asymmetrical
      frontal event-related brain responses to startle probes presented during viewing
      of affective pictures. One hundred and ten participants were shown unpleasant,
      neutral, and pleasant affective pictures, and presented startle probes during
      picture presentations. Individual differences in BIS sensitivity related to
      relatively greater right frontal N100 amplitude to startle probes presented
      during pleasant and unpleasant pictures, whereas individual differences in BAS
      sensitivity related to reduced left frontal P300 amplitude to startle probes
      presented during pleasant pictures. The results of this study suggest that BIS
      sensitivity is related to greater relative right frontal cortical activity during
      affective states, while BAS sensitivity is related to greater relative left
      frontal cortical activity during appetitive states.

PMID- 18633854
TI  - Cognitive humor processing: different logical mechanisms in nonverbal cartoons-
      an fMRI study.
AB  - Although recent fMRI studies on humor have begun to elucidate cognitive and
      affective neural correlates, they weren't able to distinguish between different
      logical mechanisms or steps of humor processing, i.e., the detection of an
      incongruity and its resolution. This fMRI study aimed to focus in more detail on
      cognitive humor processing. In order to investigate pure incongruity resolution
      without preprocessing steps, nonverbal cartoons differing in their logical
      mechanisms were contrasted with nonhumorous pictures containing an irresolvable
      incongruity. The logical mechanisms were: (1) visual puns (visual resemblance,
      PUNs); (2) semantic cartoons (pure semantic relationships, SEMs); and (3) Theory
      of Mind cartoons (which require additionally mentalizing abilities, TOMs). Thirty
      cartoons from each condition were presented to 17 healthy subjects while
      acquiring fMR images. The results reveal a left-sided network involved in pure
      incongruity resolution: e.g., temporo-parietal junction, inferior frontal gyrus
      and ventromedian prefrontal cortex. These areas are also involved in processing
      of SEMs, whereas PUNs show more activation in the extrastriate cortex and TOMs
      show more activation in so-called mentalizing areas. Processing of pictures
      containing an irresolvable incongruity evokes activation in the rostral cingulate
      zone, which might reflect error processing. We conclude that cognitive processing
      of different logical mechanisms depends on separate neural networks.

PMID- 18633855
TI  - Direct eye contact influences the neural processing of objects in 5-month-old
      infants.
AB  - Do 5-month-old infants show differences in processing objects as a function of a
      prior interaction with an adult? Using a live ERP paradigm we assessed this
      question utilizing a within-subjects design. Infants saw objects during two
      pretest phases with an adult experimenter. We recorded event-related potentials
      to the presentation of objects following the interactive pretest phases.
      Experimental conditions differed only in the nature of eye contact between the
      infant and the experimenter during the pretests. In one condition the
      experimenter engaged the infant with direct eye contact. In a second condition
      the experimenter looked only at the infant's chest. We found that the negative
      component, related to attentional processes, showed differences between
      experimental conditions in left fronto-central locations. These data show that 5
      month-old infants allocate more attention to objects that have been previously
      seen during direct eye-contact interaction. In addition, these results clarify
      the functional nature of the negative component.

PMID- 18633856
TI  - Friend or foe? Brain systems involved in the perception of dynamic signals of
      menacing and friendly social approaches.
AB  - During every social approach, humans must assess each other's intentions. Facial
      expressions provide cues to assist in these assessments via associations with
      emotion, the likelihood of affiliation, and personality. In this functional
      magnetic resonance imaging (fMRI) study, participants viewed animated male
      characters approaching them in a hallway and making either a happy or an angry
      facial expression. An expected increase in amygdala and superior temporal sulcus
      activation to the expression of anger was found. Notably, two other social brain
      regions also had an increased hemodynamic response to anger relative to
      happiness, including the lateral fusiform gyrus and a region centered in the
      middle temporal gyrus. Other brain regions showed little differentiation or an
      increased level of activity to the happy stimuli. These findings provide insight
      into the brain mechanisms involved in reading the intentions of other human
      beings in an overtly social context. In particular, they demonstrate brain
      regions sensitive to social signals of dominance and affiliation.

PMID- 18633857
TI  - EEG components of spontaneous trait inferences.
AB  - Can event-related electro-encephalogram (EEG) responses provide support for the
      occurrence of spontaneous trait inferences (STI)? Participants read sentences
      describing the behavior of a target person from which a strong trait could be
      inferred. The last word of each sentence determined the consistency with the
      trait induced during an introductory paragraph. In comparison with sentences that
      were consistent with the implied trait, when the sentences were inconsistent, an
      event-related P300 waveform was observed at parietal scalp regions (Pz). This
      dependency on behavioral consistency indicates that trait inferences were made
      spontaneously. Memory measures taken after the presentation of the stimulus
      material involved sentence completion and trait-cued recall, and also supported
      the occurrence of spontaneously inferred traits associated with the actor.
      Interestingly, increased memory for consistent relative to inconsistent behaviors
      at the trait-cued recall task was significantly correlated with the P300, which
      supports this latter measure as a valid neural correlate of spontaneous trait
      inferences.

PMID- 18633858
TI  - [Malignancies arising in sinonasal inverted papillomas].
AB  - BACKGROUND: Inverted papillomas are primarily benign neoplasms that occur in the
      nasal cavity and paranasal sinuses. Many aspects of sinonasal inverted papillomas
      are still controversial and active fields of research. Inverted papillomas
      generate considerable interest because they are locally aggressive, have a
      propensity to recur and are associated with malignancy. However, neither the
      etiology and pathogenesis of these tumors nor the putative role as a precursor to
      carcinoma and the factors responsible for associated malignancy have been
      clarified. Whether carcinomas in inverted papillomas arise meta- or synchronous
      is also still unknown. PATIENTS AND METHODS: In a retrospective study we reviewed
      the charts of 93 patients with sinonasal inverted papillomas who were treated at
      our department between 1990 and 2007. Comparison was made between the group of
      patients with inverted papillomas and associated squamous cell carcinomas and the
      group of patients with benign inverted papillomas. We undertook a critical
      analysis of our results compared with the international medical literature.
      RESULTS: Associated malignancy was found in 11 patients (11.8 %). In each one
      case a metachronous carcinoma with and without recurrent inverted papilloma was
      diagnosed, the remaining 9 carcinomas were determined to be synchronous
      malignancies. Our data suggest, that the association between carcinoma and
      inverted papilloma is indirect and that the gradual progression from inverted
      papilloma to a malignant neoplasm is if at all infrequent. Male gender, advanced
      age and recurrent inverted papilloma do not per se present risk factors for the
      development of associated malignancies. CONCLUSIONS: Sinonasal carcinomas arise
      in about 10 % of patients with inverted papillomas, but the ratio of metachronous
      carcinomas has possibly been overrated up to now. Nevertheless, regular follow-up
      investigations after surgical resection of inverted papillomas are mandatory. The
      assumption, that carcinomas in inverted papillomas are less aggressive than
      carcinomas alone and the definition of high-risk groups for the development of
      carcinomas seems hazardous.

PMID- 18633859
TI  - [Quality of life in long-term survivors after laryngectomy].
AB  - BACKGROUND: This study was designed to assess the postoperative quality of life
      (QoL) of 30 patients successfully treated with a laryngectomy. METHODS: QoL was
      evaluated with two validated questionnaires (EORTC-QLQ-C30 and EORTC-QLQ-H&N35)
      during the regular outpatient follow-up. To analyse the long-term quality of
      life, we divided our collective into two groups of patients; one consisting of
      patients whose treatment had been completed less than five years ago and one
      whose therapy had been finished more than five years ago. RESULTS: The collective
      consisted of 24 men (80 %) and 6 (20 %) women with a mean age of 58.8 +/- 8.7
      years. Mean follow-up was 53 months (range: 12 - 110). Most patients (n = 15, 50
      %) had a tumor stadium IV after UICC. Voice rehabilitation was achieved in all
      patients with a Provoxreg voice prosthesis. The global QoL was rated as
      satisfying with a mean value of 62. The analysis of the specific questionnaire
      showed mostly a limitation of smell. Patients, whose treatment was longer than
      five years ago, showed a slight improvement in the global QoL. Overall we could
      not find a significant difference concerning the QoL between the two groups.
      CONCLUSIONS: In our study the QoL of laryngectomized patients was satisfying. The
      most common symptoms were problems with smell, cough and dyspnoea.

PMID- 18633860
TI  - [Primary cutane manifestation of a precursor-B-lymphoblastic lymphoma in the
      external ear].
AB  - A Non-Hodgkin Lymphoma (NHL) represents nearly three percent of all malignant
      tumors. Thirty to fourty percent of the lymphomas are located extra-nodal. Within
      the head and neck region they might occur in the tonsils, tongue base or the
      sinuses, the larynx and the pharynx. A cutaneous manifestation is rare. We report
      on an extranodal B-cell-lymphoma of the ear in a young woman. She reported on a
      piercing of the pinna months before with a subsequent infection. This infection
      led to the development of a massive ear tumor. Histologic examination resulted in
      the final diagnosis. In spite of the considerable extent of the lymphoma there
      was no systemic manifestation and a total remission was induced by chemotherapy
      before adjuvant radiation.

PMID- 18633861
TI  - Successful endoscopic submucosal dissection of duodenal cancer.

PMID- 18633862
TI  - Chronic anemia masking a primary large B-cell lymphoma of the small intestine,
      finally diagnosed by double-balloon enteroscopy.

PMID- 18633863
TI  - An uncommon polyp in the colon: a pedunculated cavernous hemangioma.

PMID- 18633864
TI  - Small bowel perforation caused by an impacted endocapsule.

PMID- 18633865
TI  - Hemoperitoneum after colonoscopy.

PMID- 18633866
TI  - A superficial early colitic cancer that resembled a laterally spreading tumor on
      chromoendoscopy.

PMID- 18633867
TI  - Transparent hood attached to a gastroscope: a simple rescue technique for
      patients with difficult or incomplete colonoscopy.

PMID- 18633868
TI  - Embolic complications associated with endoscopic injection of cyanoacrylate for
      bleeding duodenal ulcer.

PMID- 18633869
TI  - POEMS syndrome associated with multiple hemangiomas of the small bowel and colon.

PMID- 18633870
TI  - Intestinal graft-versus-host-disease staging by video capsule endoscopy.

PMID- 18633871
TI  - Ascites infection: a novel complication of colonic stenting?

PMID- 18633872
TI  - Bizarre gastric ulcer related to betel quid use: report of two cases.

PMID- 18633873
TI  - Endoscopic treatment of duodenal perforation following laparoscopic
      cholecystectomy.

PMID- 18633874
TI  - Notched sign and bamboo-joint-like appearance in duodenal Crohn's disease.

PMID- 18633875
TI  - Expansion of metallic mesh stent hole using a Soehendra stent retriever in
      multiple stenting of biliary hilar obstruction.

PMID- 18633876
TI  - Epidermoid accessory splenic cyst masquerading as a pancreatic mucinous cystic
      neoplasm.

PMID- 18633877
TI  - Look both ways: gastrojejunocolic fistula masquerading as irritable bowel
      disease.

PMID- 18633878
TI  - Bilateral vocal cord paralysis following stent placement for proximal esophageal
      stricture.

PMID- 18633879
TI  - Fatal upper gastrointestinal bleeding caused by a metal biliary stent despite
      stent shortening with APC.

PMID- 18633880
TI  - Diffuse intramural duodenal hematoma complicated by lethal necrotizing
      pancreatitis after endoscopic duodenal biopsy.

PMID- 18633881
TI  - Post-colonoscopy tension pneumothorax resulting from colonic barotrauma in a
      previously unrecognised left-sided diaphragmatic hernia.

PMID- 18633882
TI  - Pedicled deep inferior epigastric perforator flap for lower abdominal defects and
      genital reconstructive surgery.
AB  - The pedicled deep inferior epigastric perforator (DIEP) flap can be used
      successfully to reconstruct the lower abdominal, inguinal, and genital regions.
      This muscle-sparing technique offers many advantages, such as minimal donor-site
      morbidity, a wide arch of rotation, and more versatile flap design, and provides
      for easier reconstruction than free flaps. Four pedicled DIEP flap cases are
      described in this article. The flaps were used to reconstruct lower abdominal
      defects and groin defects and to perform a penile reconstruction. To the best of
      our knowledge, ours is the first report in the English literature to describe the
      use of a pedicled DIEP flap for penile reconstruction. The donor sites were
      closed directly, and morbidity in all cases was minimal.

PMID- 18633883
TI  - Thrombotic effect of purposeful back-wall stitch for end-to-side microarterial
      anastomosis in rats.
AB  - The accidental placement of a back-wall stitch is a mistake easily made by
      microsurgeons during an end-to-side (ETS) anastomosis, which is technically more
      difficult compared with an end-to-end (ETE) anastomosis. The thrombogenic effects
      of a back-wall stitch may aggravate the already existing turbulence and therefore
      thrombus-prone ETS anastomosis. We investigated this dangerous combination by
      applying a purposeful back-wall stitch model (PBWS) in an ETS microarterial
      anastomosis model in various configurations the rat carotid and femoral arteries.
      We performed femoral and carotid artery bypass grafts via two ETS anastomosis.
      Carotid (n=28) and femoral (n=28) artery groups were equally divided into four
      different subgroups according to PBWS placement: Control (no PBWS) and 30-degree,
      60-degree, and 90-degree subgroups with PBWS located at 30, 60, and 90 degrees,
      respectively. We found that there were no significant patency differences with
      respect to vessel type, PBWS placement, or time of assessment. The results of our
      current study and previous studies demonstrate that a PBWS in the ETS anastomosis
      does not have a major effect on thrombus formation. We think that an inadvertent
      back-wall stitch in the ETS anastomosis may not be a significant cause of
      thrombosis alone but in combination with retained thrombogenic material into
      lumen can contribute to thrombus.

PMID- 18633884
TI  - [Results of antegrade intramedullar Kirschner-Wire pinning of subcapital fracture
      of the fifth metacarpal bone using Foucher's technique].
AB  - One of the most common hand injuries is the subcapital fracture of the fifth
      metacarpal bone. We propose a surgical procedure when the fracture is angulated
      for at least 40 degrees in a palmar direction or when we find a rotatory
      deformity. Our standard operation procedure is a closed reposition with an
      intramedullar Kirschner-wire pinning with 2 curved wires according to Foucher's
      technique. During the period from 8/2003 to 6/2006 we repaired 126 distal
      metacarpal fractures in the mentioned technique with the use of 1.2 mm Kirschner
      wires. We suggest an early functional aftercare with a middle hand brace for four
      weeks. In a retrospective study we were able to examine 41 patients. Our research
      included objective parameters like the grip power and the range of motion as well
      as subjective parameters with the use of the DASH score and a self-created
      questionnaire to check the individual satisfaction with the operative procedure.
      41 patients (94 %) were satisfied or very satisfied with the result of the
      operation and 35 (79 %) were satisfied or very satisfied with the local
      anaesthesia.

PMID- 18633885
TI  - [Long-term follow-up of fracture dislocations and comminuted fractures of the PIP
      joint treated with Suzuki's pin and rubber traction system].
AB  - Fracture dislocations and comminuted fractures of the PIP joint are considered as
      severe injuries with uncertain outcome. Short-term results of several traction
      devices in the treatment of PIP joint fractures have been published. But the
      further course concerning the injured joint surface has not been described yet.
      From 1995 to 2001 we treated 26 patients who suffered comminuted intraarticular
      fractures and fracture dislocations with the digital dynamic external fixator
      from Suzuki. The time of follow-up was 8 years (median) with a range of 5 - 11
      years. Due to this rather long period only 13 patients were available for follow
      up. The flexion of PIP joint gained a median value of 95 degrees (range: 35 - 100
      degrees ), extension loss was 0 degrees (median; range: 0 - 35 degrees ). Range
      of motion of the PIP joint was 85 degrees (median; range: 0 - 100 degrees ). The
      evaluation of the X-rays shows an initial anatomic reduction with complete joint
      congruency in only 20 % of the cases, but over time there was a remodelling of
      the joint surface in 89 % without obvious signs of degeneration of the joint. We
      suppose that the surprisingly good long-term results are linked to this
      extraordinary remodelling. No patient complained about pain using the affected
      finger without load and only 2 patients experienced mild pain on heavy use.
      Compared to the 2-years results of another patient group that we published in
      2001 the long-term results tend to be slightly better. We conclude that dynamic
      traction and early motion of intraarticular PIP joint fractures are the treatment
      of choice, as virtually pain-free and good motion is achieved also in the long
      term due to the remarkable remodelling capacity of the joint surface.

PMID- 18633886
TI  - [Genital elephantiasis: reconstructive treatment of penoscrotal lymphoedema with
      a myocutaneous M. gracilis flap. Experiences from a District Hospital in
      Ethiopia].
AB  - BACKGROUND: Genital elephantiasis is an illness leading to serious functional and
      aesthetic as well as psychosocial impairment. Since the 19th century there have
      been articles describing methods for surgical ablative treatment of penoscrotal
      lymphoedema. However, most of these methods ignore the creation a new drainage
      for the lymph. We now describe a new technique using a myocutaneous M. gracilis
      muscle flap for the reconstruction of the soft tissue damage resulting from
      radical excision, thus ensuring drainage of the lymph into the deep muscle
      compartment of the thigh. PATIENTS AND METHOD: In the District Hospital "Mettu
      Karl Hospital" in the Ethiopian rain forest region of Illubabor, during a period
      of 6 months the described surgical procedure was applied to 9 patients suffering
      from severe forms of this grotesquely disfiguring disease. Two patients presented
      with combined penoscrotal oedema, while the other 7 patients were suffering from
      isolated scrotal lymphoedema alone. All patients benefited from reconstruction
      with a myocutaneous M. gracilis muscle flap after radical excision of the
      affected tissue. All patients were evaluated after 3 and 12 months
      postoperatively in the presence of a translator. RESULTS: All nine patients
      showed a functionally and aesthetically satisfying result after 3 months without
      postoperative occurrence of infection. The evaluation 12 months postoperatively
      showed no recurrence of genitoscrotal lymphoedema. All patients reported on
      having regained normal ability for sexual intercourse and no occurrence of
      urinary tract infections since the operation. Concerning fertility, no statements
      could be made. A significant improvement in the quality of life was observed by
      the regained ability to walk and work and consequently the reintegration of the
      patients into their socio-economic environment. CONCLUSION: Radical excision of
      the affected tissue followed by transferring a functioning lymphatic drainage
      into the deep muscle compartment of the ipsilateral thigh using a proximally
      based myocutaneous gracilis muscle flap treats genital lymphoedema without
      recurrence. Satisfying aesthetic and functional results are achieved. The
      described surgical technique is still successfully being performed by two
      Ethiopian surgeons trained in this procedure.

PMID- 18633887
TI  - [Clinical results of terminolateral neurorrhaphy in digital nerves].
AB  - In end-to-side-neurorrhaphy the collateral sprouting of axons has been proven in
      many animal studies. It has not yet been determined if a satisfactory sensory
      recovery occurs. Unfortunately, there is still a lack of well documented clinical
      studies. We have used end-to-side nerve sutures in five patients. Four of them
      showed gaps in digital nerves, the fifth patient had a partial transsection of
      the superficial branch of the radial nerve. At the time of follow-up examination,
      surgery had been performed an average of 21 months previously (11 - 39 months).
      We examined sensibility, temperature perception, patient satisfaction and the
      presence of pain and neuroma. Two of the patients with injured digital nerves
      reached an almost normal two-point discrimination of 6 mm, the other two patients
      only achieved a value > 10 mm. With monofilaments one patient was able to
      recognise the 3.61 filament, which constitutes a standard value. The other three
      recognised the 4.31 filament, which is only one degree less. All measurements
      concerning the superficial branch of the radial nerve turned out to be less
      satisfactory, however, one must consider that the sensation qualitiy in this area
      is less to begin with. No neuromas occurred, except in the case of the radial
      nerve. None of the patients showed full recovery of temperature perception. Two
      were able to recognise a warm and three a cold probe head. Our results confirm
      the findings made in other studies which also found a clinical correlate to
      collateral axonal sprouting. Unfortunately results are still inconsistent.

PMID- 18633888
TI  - [Questions instead of being quiet--what doctors can do in cases of domestic
      violence].

PMID- 18633889
TI  - Useful endoscopic findings for early diagnosis of ulcerative colitis associated
      colorectal cancer.

PMID- 18633890
TI  - Gastric polyp in pernicious anemia: an argument to remove even when biopsy shows
      hyperplasia.

PMID- 18633891
TI  - Gastric mesh erosion after hiatoplasty for recurrent paraesophageal hernia.

PMID- 18633892
TI  - Magnifying endoscopic findings of early duodenal adenocarcinoma in relation to
      the pathological findings.

PMID- 18633893
TI  - Treatment of a pancreatic endocrine tumor by ethanol injection (PEI) guided by
      endoscopic ultrasound.

PMID- 18633894
TI  - EUS-guided rendezvous technique for difficult cannulation of an intradiverticular
      papilla.

PMID- 18633895
TI  - A novel and inexpensive model for practicing upper gastrointestinal endoscopy and
      percutaneous endoscopic gastrostomy techniques.

PMID- 18633896
TI  - Buried bumper syndrome after percutaneous endoscopic gastrostomy in children and
      adolescents.

PMID- 18633897
TI  - Retroperitoneal perforation caused by precut biliary access in a Billroth II
      gastrectomy.

PMID- 18633898
TI  - Successful en bloc resection of superficial esophageal cancer treated by
      endoscopic submucosal dissection with a splash needle.

PMID- 18633899
TI  - A novel technique for endoscopic reanastomosis in a patient with a completely
      strictured colorectal anastomosis.

PMID- 18633900
TI  - Esophageal varices and early esophageal cancer: can we perform endoscopic mucosal
      resection (EMR)?

PMID- 18633901
TI  - A rare cause of mechanical bowel obstruction in a young adult.

PMID- 18633902
TI  - Colonic stricture following conservative treatment of a colonoscopic perforation.

PMID- 18633903
TI  - Endoscopic diagnosis of secondary aortoesophageal fistula.

PMID- 18633904
TI  - Endoscopic resection of a large pedunculated duodenal polyp using a grasping type
      scissors forceps.

PMID- 18633905
TI  - Sebaceous glands in the esophagus.

PMID- 18633906
TI  - Extravasation of sclerosant after injection of N-butyl-2-cyanoacrylate for a
      bleeding gastric Dieulafoy lesion.

PMID- 18633907
TI  - Electrohydraulic lithotripsy of the common bile duct stone under transnasal
      direct cholangioscopy.

PMID- 18633908
TI  - A proposal for grading nasomucosal injury as a complication of transnasal
      endoscopy.

PMID- 18633909
TI  - Successful endoscopic treatment (clipping) of esophageal perforation during
      balloon dilatation in a patient with achalasia.

PMID- 18633910
TI  - Esophagobronchial fistula following injection sclerotherapy for esophageal
      varices.

PMID- 18633911
TI  - An admixture type of hyperplastic polyp at the esophagogastric junction.

PMID- 18633912
TI  - ERCP cannulation of a hidden papilla within a duodenal diverticulum.

PMID- 18633913
TI  - Management of severe chest pain caused by a Bravo pH monitoring capsule.

PMID- 18633914
TI  - Pneumoperitoneum following endoscopic mucosal resection without perforation of
      the colon.

PMID- 18633915
TI  - Progression of Barrett's esophagus to adenocarcinoma despite antireflux surgery.

PMID- 18633916
TI  - Treatment of hemobilia-induced biliary obstruction by transpapillary gallbladder
      and common bile duct drainage using three biliary winged stents.

PMID- 18633917
TI  - A case of colonic perforation from biliary stent.

PMID- 18633918
TI  - CSF rhinorrhea secondary to use of a Mayfield head clamp.
AB  - Various complications with use of a Mayfield head clamp have been reported, from
      minor skin necrosis and lacerations to the more significant extradural hematomas
      and meningitis. To the best of our knowledge, our report describes for the first
      time in the medical literature, the uncommon complication of frontal sinus
      fracture and cerebrospinal fluid leak caused by a scalp pin of a head clamp used
      during a frontal craniotomy. The cerebrospinal fluid leak settled with
      conservative management, and no surgical intervention was necessary. Clinicians
      should appreciate the possibility of such a complication and assess preoperative
      scans for frontal sinuses that extend to a high level, as in our patient.

PMID- 18633919
TI  - Supraglottic stenosis in localized Wegener granulomatosis.
AB  - We present what we believe is the first reported case of a patient with
      supraglottic stenosis secondary to Wegener granulomatosis. The diagnosis was
      unclear initially because the biopsy results were nonspecific, but a finding of
      an elevated cytoplasmic-pattern antineutrophil cytoplasmic antibody (c-ANCA)
      level established the diagnosis of localized supraglottic Wegener granulomatosis.
      Wegener granulomatosis is characterized by necrotizing vasculitis that is
      localized predominantly to the kidneys and the upper and lower airways. In the
      airways, subglottic involvement is well documented, but to the best of our
      knowledge, supraglottic stenosis has not previously been described. Localized
      forms of Wegener granulomatosis are characterized by limited disease that
      involves only the upper airway. The diagnosis in localized forms is complex
      because histology is diagnostic in only 50% of cases, and only 60% of patients
      have a positive c-ANCA level. We discuss the diagnostic criteria and management
      strategies for these localized forms.

PMID- 18633920
TI  - Is Susac syndrome (microangiopathy of the inner ear, retina, and central nervous
      system) an underdiagnosed cause of sensorineural hearing loss?
AB  - Susac syndrome is a rare disorder caused by the development of microangiopathic
      lesions in the inner ear, retina, and central nervous system. Although relatively
      few cases have been reported in the literature, this diagnosis is becoming more
      frequent as physician awareness increases. A high index of suspicion is needed to
      make the diagnosis because the signs and symptoms of Susac syndrome are those of
      a wide range of differential diagnoses. Otolaryngologists should be familiar with
      this syndrome because hearing loss may be the initial presenting symptom. We
      describe a new case of Susac syndrome to further promote physician awareness, and
      we discuss the options for diagnosis and treatment.

PMID- 18633921
TI  - Ectopic nasopharyngeal pituitary adenoma resected with endoscopic technique.
AB  - We describe the case of an 80-year-old man with diabetes who presented with
      nonspecific dizziness. He was found on magnetic resonance imaging to have a 3.2
      cm mass within the posterior and central aspect of the nasopharynx. Nasal
      endoscopy showed that the mass, which arose from the posterior edge of the nasal
      septum and was attached to the superior nasopharynx, was narrowing the patient's
      airway. Although initially the mass was suspected to be a minor salivary gland
      tumor, histopathologic analysis led to a diagnosis of pituitary adenoma. The
      ectopic tumor was removed via transnasal en bloc resection with partial adjacent
      septal resection. Final pathology confirmed the diagnosis. The patient had an
      uneventful recovery and no sequellae at 2-year follow-up.

PMID- 18633923
TI  - Hemotympanum.

PMID- 18633924
TI  - Hemifacial spasm.

PMID- 18633926
TI  - Anterior glottic web.

PMID- 18633927
TI  - HIV-associated lymphadenopathy.

PMID- 18633928
TI  - Failure to bill for nurse counseling: an opportunity missed.

PMID- 18633930
TI  - Extracanalicular osteoma of the temporal bone.
AB  - Extracanalicular osteomas of the temporal bone are rare, slow-growing, benign
      neoplasms. Although they may occur anywhere in the temporal bone, they are most
      common in the mastoid area. Often, symptoms are negligible and treatment is
      unnecessary. However, surgical removal is indicated when growth of the osteoma
      causes distressing symptoms or cosmetic issues. The patient described in this
      report had no symptoms but underwent surgical excision of a mastoid osteoma for
      cosmetic reasons. At 4-month follow-up, she remains asymptomatic and recurrence
      free.

PMID- 18633929
TI  - Aggressive papillary tumor of the middle ear: a true entity or an endolymphatic
      sac neoplasm?
AB  - Aggressive papillary tumors of the middle ear are rare, and their true origin is
      not clear. We describe the clinical, radiologic, genetic, and histopathologic
      features of a papillary epithelial tumor filling the middle ear of a 68-year-old
      woman. Imaging revealed no evidence of petrous temporal bone apex involvement,
      nor did genetic studies demonstrate the von Hippel-Lindau mutation. A literature
      search revealed 24 previously reported cases of such a papillary epithelial tumor
      of the middle ear. All except 2 cases demonstrated apical petrous temporal bone
      invasion on imaging, and it has been suggested that they arose from a primary
      endolymphatic sac tumor, which has a similar papillary epithelial histology.
      Substantial numbers of cases of papillary epithelial tumors involving the middle
      ear are reported to be associated with von Hippel-Lindau disease, as are known
      cases of endolymphatic sac tumor. This is the third reported case of papillary
      epithelial tumor of the middle ear that does not show apical petrous temporal
      bone invasion on imaging, suggesting that such neoplasms do not always arise from
      a primary in the endolymphatic sac.

PMID- 18633931
TI  - Angiolipoma presenting as a nasal mass: how rare a presentation?
AB  - Angiolipomas are benign adipose tumors. There are two types: infiltrating and
      noninfiltrating. An angiolipoma presenting as a nasal mass is rare. To our
      knowledge, this is only the second documented case of angiolipoma presenting in
      the nasal dorsum. Total surgical excision by an external rhinoplasty technique
      with close follow-up is advised. Recurrence is not common.

PMID- 18633932
TI  - Office CO2 laser turbinoplasty.
AB  - We conducted a prospective study of office carbon dioxide (CO(2)) laser
      turbinoplasty as a treatment for symptoms related to turbinate dysfunction in 58
      patients. All patients completed surveys before and 1 month after treatment, and
      23 patients completed longer-term follow-up surveys 8 to 24 months
      postoperatively. The 1-month postoperative assessments demonstrated a trend
      toward symptom improvement, as many patients reported a decrease in their use of
      pretreatment medications. Long-term benefit was achieved in 70% of patients. Ten
      patients underwent pre- and post-treatment biopsies, and histologic evaluation
      demonstrated minimal tissue alteration following treatment, alleviating concerns
      of physiological and functional compromise. We conclude that office-based CO(2)
      laser turbinoplasty is a useful tool for the treatment of disorders related to
      turbinate dysfunction. We describe one clinician's method of performing office
      CO(2) laser turbinoplasty, and we report his experience and findings.

PMID- 18633933
TI  - Cavernous hemangioma of the middle turbinate: a case report.
AB  - Most cavernous hemangiomas present at birth or soon after. Cavernous hemangiomas
      of the nasal cavity, which are rare, usually do not present until adulthood;
      their incidence peaks in the fourth decade of life. Most affected patients
      experience epistaxis or hemoptysis and an enlarging lesion in the nose.
      Histologically, cavernous hemangiomas appear as closely packed, dilated vascular
      channels lined with a layer of flattened endothelial cells. We describe the case
      of a 32-year-old man who was admitted to our clinic with the complaint of a nasal
      obstruction. On anterior rhinoscopy, he was found to have a hypervascularized and
      hypertrophied left middle turbinate and septal deviation. Computed tomography and
      magnetic resonance imaging of the paranasal sinuses demonstrated a well-defined
      cystic lesion that had arisen within the bony left middle turbinate and caused
      deviation of the septum to the right. The lesion was excised via endoscopic
      surgery with general anesthesia. No complications occurred during the
      postoperative period. Histologic examination identified the tumor as a cavernous
      hemangioma. To the best of our knowledge, this is the first case reported in the
      English-language literature of a cavernous hemangioma appearing as a cystic mass
      in the middle turbinate.

PMID- 18633934
TI  - Epidermoid carcinoma involving the parotid gland and orbital region: case report
      of a rare entity.
AB  - Epidermoid carcinoma (also known as squamous cell carcinoma) of the parotid gland
      is more prevalent among the elderly, as are other head and neck tumors. In most
      cases it is observed either as a nodal metastasis of a primary tumor that drains
      into the parotid area or as a direct extension of a tumor that has originated in
      the upper dermis. Primary epidermoid carcinomas arising directly from the parotid
      gland are extremely rare. Similarly, secondary invasion of the orbital region by
      a neighboring tumor is more common than primary epidermoid carcinoma of the
      orbit, which is also rare. In this article, we discuss the diagnosis and
      treatment of a rare case of epidermoid carcinoma simultaneously invading the
      parotid gland and the orbit.

PMID- 18633935
TI  - Transcervical resection of the styloid process in Eagle syndrome.
AB  - We conducted a retrospective study to determine the treatment outcomes of 6
      patients who had either unilateral or bilateral elongated styloid processes and
      symptoms consistent with Eagle syndrome. Five of these patients had undergone
      transcervical resection of the styloid process, with relief of symptoms over the
      follow-up period (mean: 8 mo). Two of the 5 patients experienced a transient
      weakness in the marginal mandibular nerve, and both recovered completely. The
      transcervical surgical approach to resection in patients with elongated styloid
      processes and Eagle syndrome appears to be safe and effective, although the risk
      for transient marginal mandibular nerve weakness is notable.

PMID- 18633936
TI  - An unusual case of adult airway obstruction from a lymphovenous malformation.
AB  - Lymphatic, venous, and mixed lymphovenous malformations are low-flow lesions that
      are present at birth and grow proportionately with the patient. We describe an
      unusual presentation of a lymphovenous malformation in an adult. A 19-year-old
      man presented to the emergency department with complaints of recent upper
      respiratory tract symptoms, increasing left-sided sore throat, voice change,
      odynophagia, dysphagia, and occasional subjective fevers and blood-tinged sputum.
      Examination revealed the presence of a left peritonsillar bulge consistent with a
      peritonsillar abscess; however, findings on needle aspiration were negative. The
      patient was admitted for intravenous steroid and antibiotic therapy. Within 24
      hours, his airway became compromised, and he underwent an awake tracheotomy and
      biopsy, which showed a lymphovenous malformation. Magnetic resonance imaging the
      following day revealed a large, poorly circumscribed, heterogeneous left
      parapharyngeal mass consistent with a vascular malformation. With continuation of
      the steroids and antibiotics, the lesion regressed, and the patient was
      subsequently decannulated. At the 1-year follow-up, he exhibited no clinical
      symptoms, and he was in good health off steroids.

PMID- 18633937
TI  - Near-complete tracheal ring deformity: a case report.
AB  - Long-segment near-complete tracheal ring deformity is a rare condition with few
      documented cases. We present the case of a 7-week-old male with total anomalous
      pulmonary venous return and long-segment near-complete tracheal rings. We discuss
      the presentation, evaluation, and management of near-complete and complete
      tracheal rings.

PMID- 18633938
TI  - New electrophoretic and chromatographic techniques for analysis of heparin and
      heparan sulfate.
AB  - Heparin (HE) and heparan sulfated glycosaminoglycans are well-known mediators of
      tissue development, maintenance and functions; the activities of these
      polysaccharides are depending mainly on their sulfate substitutions. The HE
      structure is also a very important feature in antithrombotic drug development,
      since the antithrombin binding site is composed by sequences of a specific
      sulfation pattern. The analysis of disaccharide composition is then a fundamental
      point of all the studies regarding HE/heparan sulfate glycosaminoglycan (and
      thereby proteoglycan) functions. The present work describes two analytical
      methods to quantify the disaccharides constituting HE and heparan sulfate chains.
      The use of PAGE of fluorophore-labeled saccharides and HPLC coupled with a
      fluorescence detector allowed in one run the identification of 90-95% of HE
      disaccharides and 74-100% of rat kidney purified heparan sulfate. Moreover, the
      protocol here reported avoid the N-sulfation disaccharides degradation, which may
      affect N-sulfated/N-acetylated disaccharides ratio evaluation. These methods
      could be also very important in clinical treatments since they are useful for
      monitoring the availability kinetics of antithrombotic drugs, such as low
      molecular-weight HEs.

PMID- 18633939
TI  - The application of perfluorooctanoate to investigate trimerization of the human
      immunodeficiency virus-1 gp41 ectodomain by electrophoresis.
AB  - The transmembrane glycoprotein gp41 of human immunodeficiency virus has been
      proposed to form trimer-of-hairpin during virus-cell membrane fusion. To
      investigate its oligomerization propensity under soluble and membrane-mimic
      conditions, sodium salt of perfluorooctanoate (PFO) was applied. A recombinant
      gp41 ectodomain devoid of disulfide linkage was overexpressed in Escherichia coli
      and characterized by MS and circular dichroism spectropolarimetry in PFO solution
      in comparison to SDS. The helical content of this ectodomain in PFO is higher
      than that in SDS. Notably, PFO employed in PAGE clearly conduced to the formation
      of trimer under the optimized condition as visualized in the gel. In addition,
      the proteins expressed from the two mutants in the heptad repeat (HR) domains of
      gp41, I62P, and N126K, were also examined by the PFO-PAGE analysis for functional
      ramification of molecular organization. Remarkably, the I62P mutation completely
      abolished the gp41 trimer formation, whereas the N126K mutation resulted in a
      more stable trimer. The data suggested that PFO-PAGE analysis is appropriate for
      evaluating the effect of mutations on the trimerization of gp41 and other fusion
      proteins which may be implicated in the alteration of their fusogenicity.

PMID- 18633940
TI  - Modification of the immobilized metal affinity electrophoresis using sodium
      dodecyl sulfate polyacrylamide gel electrophoresis.
AB  - Modification to the original immobilized metal affinity electrophoresis (IMAEP)
      technique is presented. SDS-PAGE is used instead of native PAGE for improved
      extraction of phosphoproteins from a mixture of proteins. Protein samples treated
      with 2% w/v SDS instead of native sample buffer ensure that proteins are
      negatively charged. These negative charges on the proteins assure that the
      proteins migrate electrophoretically towards the anode regardless of their pI
      values and hence pass through the region embedded with the metal ions. Another
      benefit of treating proteins with SDS is that it unfolds the phosphoproteins
      exposing the phosphate groups to facilitate the metal-phosphate interactions.
      Phosphorylated ovalbumin can only be extracted after SDS sample buffer treatment.
      Data show that there is no detrimental effect upon SDS treatment on the
      extraction of phosphoproteins from a mixture of proteins. Electrophoretic
      migration of phosphoproteins ceases upon encounter with metal ions like Al+3,
      Ti+3, Fe+3, Fe+2, and Mn+2 whereas non-phosphorylated proteins migrate freely.

PMID- 18633941
TI  - Metabolic fingerprinting of Schistosoma mansoni infection in mice urine with
      capillary electrophoresis.
AB  - Schistosoma mansoni infection in mice has been fingerprinted using CE to study
      the capabilities of this technique as a diagnostic tool for this parasitic
      disease. Two modes of separation were used in generating the electrophoretic
      data, with each untreated urine sample the following methods were applied: (i) a
      fused-silica capillary, operating with an applied potential of 18 kV, in micellar
      EKC (MEKC) and (ii) a polyacrylamide-coated capillary, operating with an applied
      potential of -20 kV under zonal CZE conditions. By combining normal and reverse
      polarities in the data treatment we have extracted more information from the
      samples, which is a better approach for CE metabolomics. The traditional problems
      associated with variability in electrophoretic peak migration times for analytes
      were countered by using a dynamic programming algorithm for the electropherograms
      alignment. Principal component analyses of these aligned electropherograms and
      partial least square discriminant analysis (PLS-DA) data are shown to provide a
      valuable means of rapid and sample classification. This approach may become an
      important tool for the identification of biomarkers, diagnosis and disease
      surveillance.

PMID- 18633942
TI  - Determination of levofloxacin and norfloxacin by capillary electrophoresis with
      electrochemiluminescence detection and applications in human urine.
AB  - A novel method for the determination of norfloxacin (NOR) and levofloxacin (LVX)
      was developed by CE separation and electrochemiluminesence detection (ECL). The
      methods for capillary conditioning and the effect of solvent type were studied.
      Parameters affecting the CE and ECL were also investigated. Under the optimum
      conditions, the two analytes were well separated within 9 min. The LODs (S/N = 3)
      in standard solution are 4.8 x 10(-7) mol/L for NOR and 6.4 x 10(-7) mol/L for
      LVX, respectively. The precisions of intraday and interday are less than 4.2 and
      8.1%, respectively. The LOQs (S/N = 10) in real human urine samples are 1.2 x 10(
      6) mol/L for NOR and 1.4 x 10(-6) mol/L for LVX, respectively. The applicability
      of the proposed method was illustrated in the determination of NOR and LVX in
      human urine samples and the monitoring of pharmacokinetics for NOR. The
      recoveries of NOR and LVX at different levels in human urine samples were between
      84.3 and 92.3%.

PMID- 18633944
TI  - Interactions between thrombin and natural products of Millettia speciosa Champ.
      using capillary zone electrophoresis.
AB  - In Chinese medicine Suberect Spatholobus Stem is used to treat menoxenia, blood
      deficiency, numb paralyses, and so on. In folk, Millettia speciosa is often used
      as a substitute for Suberect Spatholobus Stem in some areas but it has not been
      reported whether M. speciosa is the eligible substitute for Suberect Spatholobus
      Stem or not till now. In this study, a capillary zone electrophoretic method was
      applied to determinate the interactions between natural products isolated from M.
      speciosa Champ. and thrombin for the first time. Both qualitative and
      quantitative characterizations of the molecule-enzyme binding were determined.
      Twenty ingredients were isolated from M. speciosa Champ. and the results showed
      that compared with positive and negative control, the compounds YT-1, YT-2, YT-3,
      YT-8, YT-9, YT-10, YT-11, YT-12, YT-14, YT-15, YT-16, and YT-20 interacted with
      thrombin while the other eight had no binding to thrombin. The binding constants
      of the interaction between compounds and thrombin were calculated by the
      Scatchard analysis formula. Because M. speciosa contains these compounds which
      have different levels of anticoagulant activity, it may be the eligible
      substitute for Suberect Spatholobus Stem.

PMID- 18633943
TI  - Capillary electrophoresis of complex natural polysaccharides.
AB  - Complex natural polysaccharides, glycosaminoglycans (GAGs), are a class of
      ubiquitous macromolecules that exhibit a wide range of biological functions and
      participate and regulate multiple cellular events and (patho)physiological
      processes. They are generally present either as free chains (hyaluronic acid and
      bacterial acidic polysaccharides) or as side chains of proteoglycans (PGs;
      chondroitin/dermatan sulfate, heparin/heparan sulfate, and keratan sulfate) and
      are most often found in cell membranes and in the extracellular matrix. The
      recent emergence of modern analytical tools for their study has produced a
      virtual explosion in the field of glycomics. CE, due to its high resolving power
      and sensitivity, has been useful in the analysis of intact GAGs and GAG-derived
      oligosaccharides and disaccharides affording concentration and structural
      characterization data essential for understanding the biological functions of
      GAGs. In this review, novel off-line and on-line CE-MS and MS/MS methods for
      screening of GAG-derived oligosaccharides and disaccharides will be discussed.

PMID- 18633945
TI  - Influence of polymer structure on electroosmotic flow and separation efficiency
      in successive multiple ionic layer coatings for microchip electrophoresis.
AB  - The effect of successive multiple ionic layer (SMIL) coatings on the velocity and
      direction of EOF and the separation efficiency for PDMS electrophoresis
      microchips was studied using different polymer structures and deposition
      conditions. To date, the majority of SMIL studies have used traditional CE and
      fused-silica capillaries. EOF was measured as a function of polymer structure and
      number of layers, in one case using the same anionic polymer and varying the
      cationic polymer and in the second case using the same cationic polymer and
      varying the anionic polymer. In both situations, the EOF direction reversed with
      each additional deposited polymer layer. The absolute EOF magnitude, however, did
      not vary significantly with layer number or polymer structure. Next, different
      coatings were used to compare separation efficiencies on native and SMIL-coated
      PDMS microchips. For native PDMS microchips, the average separation efficiency
      was 4105 +/- 1540 theoretical plates. The addition of two layers of polymer
      increased the separation efficiency anywhere from two- to five-fold, depending on
      the polymer structure. A maximum separation efficiency of 12 880 +/- 1050
      theoretical plates was achieved for SMIL coatings of polybrene (cationic) and
      dextran sulfate (anionic) polymers after deposition of six total layers. It was
      also noted that coating improved run-to-run consistency of the peaks as noted by
      a reduction of the RSD of the EOF and separation efficiency. This study shows
      that the use of polyelectrolyte coatings, irrespective of the polymer structure,
      generates a consistent EOF in the current experiments and dramatically improves
      the separation efficiency when compared to unmodified PDMS microchips.

PMID- 18633946
TI  - Competitive immunoassay by capillary electrophoresis with laser-induced
      fluorescence for the trace detection of chloramphenicol in animal-derived foods.
AB  - A competitive immunoassay using CE with an LIF detector was developed for the
      detection of chloramphenicol (CAP). The method was based on the competitive
      reactions between fluorescently labeled CAP hapten and free CAP, with a limited
      amount of anti-CAP antibody. The poly(N-isopropylacrylamide) (pNIPA) hydrogel was
      added in the separation buffer as a dynamic modifier to reduce adsorption and
      enhance reproducibility. The linear range and LOD for CAP were 0.008-5 microg/L
      and 0.0016 microg/L, respectively. An ELISA using the same immuno-reagents was
      also developed for the analysis of CAP, with an LOD of 0.03 microg/L. The
      sensitivity of this CE immunoassay (CEIA)-LIF was almost 20 times greater than
      that of the ELISA. Using CEIA-LIF, equilibrium was reached in 15 min and the
      analytical results were obtained within 5 min by CE separation. Sample
      preparation for CEIA-LIF was not time-consuming and the matrix effect was easy to
      remove. An LOD of 0.1 microg/kg CAP in food matrices was easily achieved. This
      method is thus proposed as a fast and sensitive means of detecting trace amounts
      of CAP residues in animal-derived foods.

PMID- 18633947
TI  - Dissociation of SO2 on Au/TiC(001): effects of Au-C interactions and charge
      polarization.

PMID- 18633948
TI  - Single-molecule imaging of rotaxanes immobilized on glass substrates: observation
      of rotary movement.

PMID- 18633949
TI  - Liquid-crystal engineering with anchor-shaped molecules: honeycombs with
      hexagonal and trigonal symmetries formed by polyphilic bent-core molecules.

PMID- 18633950
TI  - Synthesis and biological activity of largazole and derivatives.

PMID- 18633951
TI  - 8-pCPT-2'-O-Me-cAMP-AM: an improved Epac-selective cAMP analogue.

PMID- 18633952
TI  - Iron- and ruthenium-Lewis acid catalyzed asymmetric 1,3-dipolar cycloaddition
      reactions between enals and diaryl nitrones.
AB  - The highly tuned, one-point binding cationic cyclopentadienyl-iron and -ruthenium
      complexes 1 and 2 that incorporate chiral bidentate pentafluoroaryl-phosphinite
      ligands selectively coordinate and activate alpha,beta-unsaturated carbonyl
      compounds towards asymmetric catalytic cycloaddition reactions with diaryl
      nitrones. The reaction gives isoxazolidine products in good yields, with complete
      endo selectivity and high enantioselectivity. The products are obtained as a
      mixture of regioisomers in ratios varying from 96:4 to 15:85. The
      regioselectivity correlates directly with the electronic properties of the
      nitrone. This is shown by the experimental and computational data.

PMID- 18633953
TI  - Total synthesis of an anti-Helicobacter pylori agent, actinopyrone A.
AB  - Actinopyrone A, an anti-Helicobacter pylori agent, was synthesized in nine steps
      from a silyl dienol ether. A vinylogous anti-aldol was stereoselectively
      synthesized by our developed remote stereoinduction methodology; coupling of this
      with a sulfone and a phosphonate species led to the construction of a vinylpyrone
      compound. This was submitted to reductive de-conjugation to give actinopyrone A.
      The absolute stereochemistry of actinopyrone A was determined to have the
      configuration 14R,15R.

PMID- 18633954
TI  - Molecular design of specific metal-binding peptide sequences from protein
      fragments: theory and experiment.
AB  - A novel strategy is presented for designing peptides with specific metal-ion
      chelation sites, based on linking computationally predicted ion-specific
      combinations of amino acid side chains coordinated at the vertices of the desired
      coordination polyhedron into a single polypeptide chain. With this aim, a series
      of computer programs have been written that 1) creates a structural combinatorial
      library containing Zi-(X)n-Zj sequences (n=0-14; Z: amino acid that binds the
      metal through the side chain; X: any amino acid) from the existing protein
      structures in the non-redundant Protein Data Bank; 2) merges these fragments into
      a single Z1-(X)n1 -Z2-(X)n2 -Z3-(X)n3 -...-Zj polypeptide chain; and 3)
      automatically performs two simple molecular mechanics calculations that make it
      possible to estimate the internal strain in the newly designed peptide. The
      application of this procedure for the most M2+-specific combinations of amino
      acid side chains (M: metal; see L. Rulisek, Z. Havlas J. Phys. Chem. B 2003, 107,
      2376-2385) yielded several peptide sequences (with lengths of 6-20 amino acids)
      with the potential for specific binding with six metal ions (Co2+, Ni2+, Cu2+,
      Zn2+, Cd2+ and Hg2+). The gas-phase association constants of the studied metal
      ions with these de novo designed peptides were experimentally determined by MALDI
      mass spectrometry by using 3,4,5-trihydroxyacetophenone as a matrix, whereas the
      thermodynamic parameters of the metal-ion coordination in the condensed phase
      were measured by isothermal titration calorimetry (ITC), chelatometry and NMR
      spectroscopy methods. The data indicate that some of the computationally
      predicted peptides are potential M2+-specific metal-ion chelators.

PMID- 18633955
TI  - Direct bonds between metal atoms: Zn, Cd, and Hg compounds with metal-metal
      bonds.
AB  - The synthesis and characterization of [Zn(2)(eta(5)-C(5)Me(5))(2)], a stable
      molecular compound with a Zn-Zn bond and the first example of a dimetallocene
      structure, has opened a new chapter in the organometallic chemistry of zinc and
      in metallocene chemistry. The existence of two directly bonded zinc atoms
      demonstrates that the [Zn-Zn](2+) unit, the lightest Group 12 homologue of the
      well-known [Hg-Hg](2+) ion, can be stabilized by appropriate ligands. Activity in
      this area has increased enormously in the few years since the determination of
      the structure of this molecule. Numerous theoretical studies have been devoted to
      the investigation of the electronic, structural, and spectroscopic properties of
      this and related compounds, and new metal-metal coordination and organometallic
      compounds of zinc, cadmium, and mercury have been synthesized and structurally
      characterized. This Minireview gives an overview of activity in this field during
      the past three to four years.

PMID- 18633956
TI  - Biocatalysis using gelatin microemulsion-based organogels containing immobilized
      Chromobacterium viscosum lipase.
AB  - Chromobacterium viscosum (CV) lipase was immobilized in gelatin-containing
      Aerosol-OT (AOT) microemulsion-based organogels (MBGs). The behavior of this
      novel, predominantly hydrophobic matrix as an esterification catalyst has been
      examined. The biocatalyst was most effective when the MBG was granulated to yield
      gel particles of approximately 500 mum diameter, providing a total surface area
      of ca. 10(6) mm(2) per 10 cm(3) of gel. The gel was generally contacted with a
      solution of the substrate(s) in a hydrocarbon oil. Under most conditions reaction
      was not diffusion limited. Apparent lipase activity was influenced by certain
      compositional changes in the MBG, but most significantly when the R value, the
      mole ratio of water to surfactant, was altered. Higher activities were observed
      at lower R values. Although gels of lowest R value expressed the highest
      condensation activity, such formulations were physically unsuitable as
      immobilization matrices due to their proximity to the gel-solution phase
      boundary. MBGs of intermediate R values (between 60 and 80) were considered most
      suitable because they offer relatively high condensation activity and good
      physical stability. The gelatin concentration also exerted a small but measurable
      influence on the observed condensation rates. Apparent lipase activity was also
      influenced to some extent by the nature of the parent hydrocarbon used to prepare
      the MBG. Higher activities were obtained using formulations derived from
      isooctane and cyclohexane rather than the n-alkanes. Condensation activities
      expressed by CV lipase in the MBGs were broadly comparable to those expressed in
      the analogous parent water-in-oil (w/o) microemulsions. The MBGs functioned
      effectively in neat substrate solutions, but the condensation activity expressed
      by the MBGs in a series of successive batch syntheses was adversely affected by
      the formation and retention of the water coproduct. Selective removal of the
      water was achieved using a concentrated solution of dry reverse micelles, which
      resulted in recovery of lost activity. Pretreatment of lipase-containing MBGs
      resulted in the formation of MBGs with enhanced catalytic properties and modified
      composing the conventional procedure. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633957
TI  - Metabolic engineering and control analysis for production of aromatics: Role of
      transaldolase.
AB  - Aromatic metabolites in Escherichia coli and other microorganisms are derived
      from two common precursors: phosphoenolpyruvate (PEP) and erythrose 4-phosphate
      (E4P). During growth on glucose, the levels of both E4P and PEP are insufficient
      for high throughput of aromatics because of the low carbon flux through the
      pentose pathway and the use of PEP in the phosphotransferase system. It has been
      shown that transketolase and PEP synthase are effective in relieving this
      limitation and promoting high throughput of aromatics. To determine whether
      transaldolase, another E4P-producing enzyme, is also a limiting factor in
      directing carbon flux to the aromatic pathway, E. coli transaldolase gene (tal)
      was cloned and overexpressed in an aroB strain which excretes 3-deoxy-D
      arabinoheptulosonate-7-phosphate (DAHP), the first intermediate in the aromatic
      pathway. We found that overexpression of transaldolase did significantly increase
      the production of DAHP from glucose. This result further supports the contention
      that the supply of E4P is limiting when glucose is the carbon source. However,
      overexpression of transaldolase in strains which already overexpress
      transketolase did not show a further increase in production of aromatics. This
      result was attributed to the saturation of E4P supply when TktA was
      overexpressed. The flux control of DAHP production was discussed on the basis of
      Metabolic Control Analysis. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633958
TI  - Simulation of growth of a filamentous fungus in 3 dimensions.
AB  - The tridimensional growth of a filamentous fungus was simulated, based on a model
      for the evolution of the microscopic morphology of Trichoderma reesei. When
      supplemented with a spatial representation of growth, the model correctly
      simulates the evolution from a single spore to a pellet. Diffusion of oxygen is
      included in the model. The simulated tridimensional structures have a fractal
      nature; and the fractal dimension, determined by a box-counting method, increases
      during growth. The fractal dimension only depends on the mass of the pellet and
      is not affected by model parameters such as tip extension rate and branching
      frequency. Realistic pictures are obtained and the radius of the pellet increases
      at a constant rate. The influence of model parameters (tip extension rate,
      branching frequency, minimum porosity) on dissolved oxygen concentration
      profiles, biomass concentration profiles, rate at which the pellet diameter
      increases, and the evolution of the fractal dimension was determined. The
      dissolved oxygen profiles were found to be very different from the profiles,
      obtained by assuming a homogenous biomass distribution within the pellet.
      Finally, the formation of pellets from spore aggregates is calculated and the
      size of the spore aggregate is found to only influence the time needed before the
      appearance of a pellet and not its morphology. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633959
TI  - Measurement of local diffusion coefficients in biofilms by microinjection and
      confocal microscopy.
AB  - A new technique for the determination of local diffusion coefficients in biofilms
      is described. It is based on the microinjection of fluorescent dyes and
      quantitative analysis of the subsequent plume formation using confocal laser
      microscopy. The diffusion coefficients of fluorescein (MW 332), TRITC-IgG (MW
      150000) and phycoerythrin (MW 240000) were measured in the cell clusters and
      interstitial voids of a heterogeneous biofilm. The diffusivities measured in the
      voids were close to the theoretical values in water. Fluorescein had the same
      diffusivity in cell clusters, voids, and sterile medium. TRITC-IgG did not
      diffuse in cell clusters, presumably due to binding to the cell cluster matrix.
      After treatment of the biofilm with bovine serum albumin, binding capacity
      decreased and the diffusion coefficient could be measured. The diffusivity of
      phycoerythrin in cell clusters was impeded by 41%, compared to interstitial
      voids. From the diffusion data of phycoerythrin it was further calculated that
      the cell cluster matrix had the characteristics of a gel with 0.6 nm thick fibers
      and pore diameters of 80 nm. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633960
TI  - Nitrogen compounds in wine during its biological aging by two flor film yeasts:
      An approach to accelerated biological aging of dry sherry-type wines.
AB  - Urea, ammonium, and free amino acid contents were quantified in biological aging
      of a young wine under two flor film forming yeast strains, Saccharomyces
      cerevisiae race capensis and S. cerevisiae race bayanus, and compared. Cell
      viability in the film was different for the two yeast strains. Thus, capensis
      maintained a much greater number of viable cells per surface area than bayanus
      and hence used greater amount of nitrogen compounds. The main source of nitrogen
      for the yeasts during the biological aging process was L-proline. The two yeast
      strains also differed in the amounts of assimilable nitrogen they utilized, in
      their preferences for amino acid consumption, and kinetics. To accelerate the
      aging process, the effect of controlled monthly aeration of the wine aged with
      capensis strain was investigated. The results revealed that short aeration did
      not appreciably increase the overall consumption of assimilable nitrogen, but
      consumption of some nitrogen compounds was accelerated (particularly L-proline, L
      tryptophan, L-glutamic acid, ammonium ion, L-lysine, and L-arginine); the use of
      L-ornithine was inhibited; and GABA, L-methionine, and urea were depletes.
      Probably the aeration increases the aroma compounds, thereby producing wines with
      improved sensory properties. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633961
TI  - Influence of dissolved oxygen concentration on nitrite accumulation in a biofilm
      airlift suspension reactor.
AB  - The biofilm airlift suspension (BAS) reactor can treat wastewater at a high
      volumetric loading rate combined with a low sludge loading. Two BAS reactors were
      operated, with an ammonium load of 5 kg N/(m(3) d), in order to study the
      influence of biomass and oxygen concentration on the nitrification process. After
      start-up the nitrifying biomass in the reactors gradually increased up to 30 g
      VSS/L. Due to this increased biomass concentration the gas-liquid mass transfer
      coefficient was negatively influenced. The resulting gradual decrease in
      dissolved oxygen concentration (over a 2-month period) was associated with a
      concomitantly nitrite build-up. Short term experiments showed a similar relation
      between dissolved oxygen concentration (DO) and nitrite accumulation. It was
      possible to obtain full ammonium conversion with approximately 50% nitrate and
      50% nitrite in the effluent. The facts that (i) nitrite build up occurred only
      when DO dropped, (ii) the nitrite formation was stable over long periods, and
      (iii) fully depending on DO levels in short term experiments, led to the
      conclusion that it was not affected by microbial adaptations but associated with
      intrinsic characteristics of the microbial growth system. A simple biofilm model
      based on the often reported difference of oxygen affinity between ammonium and
      nitrite oxydizers was capable of adequately describing the phenomena.Measurements
      of biomass density and concentration are critical for the interpretation of the
      results, but highly sensitive to sampling procedures. Therefore we have developed
      an independent method, based on the residence time of Dextran Blue, to check the
      experimental methods. There was a good agreement between procedures.The relation
      between biomass concentration, oxygen mass transfer rate and nitrification in a
      BAS reactor is discussed. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633962
TI  - On-line measurement and analysis of yeast flocculation.
AB  - The ability of yeast to flocculate is important in different separation
      processes, especially in the beer industry. Because of the regulation purposes,
      there is a need for online monitoring. With the presented measuring set-up,
      consisting of a peristaltic pump, a photometer, and a computer, it is possible to
      determine the onset of flocculation as well as to follow flocculation intensity
      and the concentration of nonflocculated cells. It was found that for the yeast
      strain Saccharomyces cerevisiae ZIM 198 the decrease of nonflocculated cells
      (after flocculation has occurred) during the exponential growth can be described
      by an exponential equation for the first-order process, whereas the increase of
      free cells due to dispersion of the flocs during the stationary phase follows the
      form of the growth curve. It was also demonstrated that the absorbency profiles
      of yeast sedimentation can be described by the second-order equation suggested by
      Stradford and Keenan for the decrease of cell concentration during sedimentation.
      (c) 1997 John Wiley & Sons, Inc.

PMID- 18633963
TI  - Production of antioxidant vitamins, beta-carotene, vitamin C, and vitamin E, by
      two-step culture of Euglena gracilis Z.
AB  - Euglena gracilis Z is one of the few microorganisms which simultaneously produces
      antioxidant vitamins such as beta-carotene and vitamins C and E.
      Photoheterotrophically cultured E. gracilis Z produced larger levels of biomass
      but with a lower content of antioxidant vitamins than photoautotrophically grown
      cultures. For efficient production of these vitamins, a two-step culture was
      performed. Cells were grown photoheterotrophically and then transferred to
      photoautotrophic conditions. When E. gracilis Z cells were grown in fed-batch
      culture under photoheterotrophic conditions, their density reached 19 g/L after
      145 h. Subsequent transfer of these cells to photoautotrophic conditions
      increased vitamin content, enhancing the total vitamin yields, which were 71.0
      mg/L of beta-carotene, 30.1 mg/L of vitamin E, and 86.5 mg/L of vitamin C. (c)
      1997 John Wiley & Sons, Inc.

PMID- 18633964
TI  - Morphological characterization of filamentous microorganisms in submerged
      cultures by on-line digital image analysis and pattern recognition.
AB  - The morphology of filamentous microorganisms in submerged culture is of great
      interest. On the one hand, morphology influences rheology and mass transfer in
      the fermentation broth. On the other hand, morphology could be a visible
      expression of physiology and metabolism of the microorganisms. An algorithm for
      the morphological characterization and the estimation of biomass of filamentous
      microorganisms by means of digital image analysis has been developed. After
      measurement of eight features the objects in the broth are classified into
      different morphological classes, i.e., pellet aggregates, rough pellets, smooth
      pellets, mycelial flocks, and medium components. The classification is based on
      the measured object parameters and a knowledge base, which was generated in a
      preceding training phase. The method was tested on Streptomyces tendae Tu 901/8c.
      A typical batch fermentation in a defined medium is presented. It could be shown
      that both morphology and physiology have been changed in the course of the
      fermentation, especially during the transition from trophophase to idiophase. In
      order to supervise the fermentation processes continuously, an on-line image
      analysis system has been developed. Sampling, dilution, and image acquisition of
      the culture were performed under the control of a personal computer. (c) 1997
      John Wiley & Sons, Inc.

PMID- 18633965
TI  - Initial protein concentration effects on precipitation by salt.
AB  - The influence of initial protein concentration on the performance of salting-out
      precipitation is examined. In the precipitation of bovine albumin by ammonium
      sulfate, a peak occurs in the plot of protein solubility versus initial protein
      concentration; that is, the solubility first increases and then falls with
      increasing initial protein concentration. In addition, the dependence of
      solubility on the initial protein concentration is less significant if using
      higher salt concentrations. The solubility behavior of bovine albumin may be
      representative, because it covers all possible alternatives; namely, the
      solubility is independent of, increases with, decreases with, or first increases
      and then decreases with the initial protein concentration. The appearance of a
      solubility peak can be explained based on the occurrence of a primary particle
      during the precipitation process. However, inclusion of the influence of initial
      protein concentration into the Cohn equation is not feasible with the use of a
      logarithmic scale, which does not sensitively reflect the change in protein
      solubility. Increasing initial protein concentration favors protein recovery
      because it reduces the resultant volume of the supernatant phase. (c) l997 John
      Wiley & Sons, Inc.

PMID- 18633966
TI  - Application of mineral support on cephamycin C production in culture using
      soybean oil as the sole carbon source.
AB  - A mineral support was used for cephamycin C production in a culture using soybean
      oil as the sole carbon source. When the support was added into an oil-water
      system, the soybean oil was emulsified as fine oil droplets, which was observed
      by a photomicroscope. Mycelia were also twined around the support, which was
      observed by a scanning electron microscope. That caused the formation of an oil
      mycelia complex on or around the support, which provided a larger specific
      surface area of oil. When 15 g/L of the support was used in a batch culture of
      Streptomyces sp. P6621 with 50 g/L of soybean oil, the maximum cephamycin C
      concentration was 2.8 g/L, which was 2.2 times higher than that without the
      support. This indicates that the mineral support is useful for the culture system
      using vegetable oil as a carbon source. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633967
TI  - Taxol (paclitaxel) production using free and immobilized cells of Taxus
      cuspidata.
AB  - The production characteristics for Taxol (paclitaxel) using free and immobilized
      cells of Taxus cuspidata were investigated in a perfusion culture bioreactor.
      Although the cell growth was inhibited by higher dilution rates, the specific
      production rate of Taxol was increased by perfusion compared with that using
      batch operation. Perfusion cultures using a nylon-mesh cell separator for free
      suspension cells showed similar production profiles to those obtained using
      immobilized cells. Continuous Taxol production was successfully obtained at an
      approximate specific production rate of 0.3 mg/g DCW (dry cell weight) per day
      for up to 40 days. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633968
TI  - Intrinsic kinetic parameters of substrate utilization by immobilized anaerobic
      sludge.
AB  - This article presents a method for evaluating the intrinsic kinetic parameters of
      the specific substrate utilization rate (r) equation and discusses the results
      obtained for anaerobic sludge-bed samples taken from a horizontal-flow anaerobic
      immobilized sludge (HAIS) reactor. This method utilizes a differential reactor
      filled with polyurethane foam matrices containing immobilized anaerobic sludge
      which is subjected to a range of feeding substrate flow rates. The range of
      liquid superficial velocities thus obtained are used for generating data of
      observed specific substrate utilization rates (r(obs)) under a diversity of
      external mass transfer resistance conditions. The r(obs) curves are then adjusted
      to permit their extrapolation for the condition of no external mass transfer
      resistance, and the values determined are used as a test for the condition of
      absence of limitation of internal mass transfer. The intrinsic parameters r(max),
      the maximum specific substrate utilization rate, and K(s), the half-velocity
      coefficient, are evaluated from the r values under no external mass transfer
      resistance and no internal mass transfer limitation. The application of such a
      method for anaerobic sludge immobilized in polyurethane foam particles treating a
      glucose substrate at 30 degrees C resulted in intrinsic r(max) and K(s),
      respectively, of 0.330 mg chemical oxygen demand (COD) . mg(-1) volatile
      suspended solids (VSS) . h(-1) and 72 mg COD . L(-1). In comparison with the
      values found in the literature, intrinsic r(max) is significantly high and
      intrinsic K(s) is relatively low. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633969
TI  - Bacitracin significantly reduces degradation of peptides in plant cell cultures.
AB  - Production of useful peptides using recombinant plant cells is often limited by
      the stability of the newly translated peptides in the plant expression system. As
      an initial step toward producing peptides in transformed plant cell cultures, we
      examined the stability of exogenously added arginine vasopressin (AVP) peptide in
      a suspension culture of Nicotiana plumbaginifolia cells. The peptide was lost
      rapidly from the plant cell culture, but the rate of loss was slowed
      significantly by the addition of the peptide, bacitracin, at a concentration of
      150 mug/mL. At higher concentrations, bacitracin substantially inhibited the
      growth of the plant cells in culture. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633970
TI  - Production of micronic particles of biocompatible polymer using supercritical
      carbon dioxide.
AB  - Three micronization techniques, based on the use of supercritical carbon dioxide,
      were investigated to produce microspheres of a natural biocompatible
      polysaccharide. Particles smaller than 20 mum were obtained by means of the rapid
      expansion of a supercritical solution method (RESS), both with and without
      cosolvents. The mean diameter of the particles was reduced to about 0.5 mum when
      a solution of the polymer in an organic solvent was expanded by using carbon
      dioxide as a supercritical antisolvent (SAS). The SAS process was operated both
      in a continuous and in a batch mode. The former leads to aggregated structures
      and fibers, and the latter to the formation of micronic spherical particles. It
      was found that the experimental temperature did not substantially affect the
      shape and dimension of the particles. A stronger dependence is shown with respect
      to the solute concentration in the starting solution. The proposed method is
      attractive as the basis of a new process for the preparation of drug delivery
      systems. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633971
TI  - Bacterial motility, collisions, and aggregation in a 3-mum-diameter capillary.
AB  - Motility of Escherichia coli K-12 cells was studied in a capillary tube with an
      inside diameter of 3 mum, which is comparable to the size of the cells' body. The
      extreme restriction, imposed by the capillary on the bacterial motility, caused a
      series of phenomena such as cell aggregation, swimming as a cluster, and break-up
      of aggregates, which were observable for the first time, and which are reported
      here. (c) 1997 John Wiley & Sons, Inc.

PMID- 18633972
TI  - Lectin precipitation using phytohemagglutinin-L(4) coupled to avidin-agarose for
      serological biomarker discovery in colorectal cancer.
AB  - N-acetylglucosaminyltransferase V (GnT-V) has been reported to be upregulated in
      malignant cancer cells, and its targets have been sought after with regard to
      biomarker identification. The low capacity and high false positive rates of 2-DE
      gel-based lectin blots using phytohemagglutinin-L(4) (L-PHA) prompted us to
      develop a novel protocol for identifying GnT-V targets, in which serum proteins
      were subjected to immunodepletion, alkylation, and lectin precipitation using L
      PHA coupled to avidin-agarose bead complexes, and tryptic digestion. Proteins
      captured by L-PHA conjugates were analyzed by a nano-LC-FT-ICR/LTQ MS. Here, we
      report 26 candidate biomarkers for colorectal cancer (CRC) that show 100%
      specificity and sensitivities of greater than 50%. Not only can these candidate
      proteins be used as analytes for validation, but the novel protocol described
      herein can be applied to biomarker discovery in nonCRCs.

PMID- 18633973
TI  - Disease associations and family-based tests.
AB  - This unit describes the statistical techniques necessary for performing family
      based association studies (such as the TDT) for genetic polymorphisms. Such
      studies have become increasingly important in the identification of genes that
      confer an increased risk to disease, particularly for common diseases with a
      complex etiology. The family-based approach avoids some of the problems often
      encountered when applying the traditional case-control design to genetic studies.
      The unit includes the Sib TDT (S-TDT) method, which allows application of the
      principle of the TDT to sibships without parental data, and several related
      tests.

PMID- 18633974
TI  - High-throughput quantitative real-time PCR.
AB  - Recent technical advances in quantitative real-time PCR (qRT-PCR) have allowed
      for extensive miniaturization, thereby rendering the technique amenable to high
      throughput assays. Large numbers of different nucleic acids can now rapidly be
      measured quantitatively. Many investigations can benefit from this approach,
      including determination of gene expression in hundreds of samples, determination
      of hundreds of genes in a few samples, or even quantification of nucleic acids
      other than mRNA. A simple technique is described here to quantify 1880
      transcripts of choice from any number of starting RNA samples.

PMID- 18633975
TI  - Investigational methods for peroxisomal disorders.
AB  - Peroxisomes play an important role in cellular metabolism. Defects in peroxisome
      assembly or of a single peroxisomal pathway are associated with a wide variety of
      inherited disorders, including X-linked adrenoleukodystrophy, Zellweger spectrum
      disorders, rhizomelic chondrodysplasia punctata, and Refsum disease. A group of
      peroxisome-specific biomarkers has been shown to be characteristic of specific
      defects. Patients with defects in peroxisome fatty acid beta-oxidation accumulate
      very long-chain fatty acids (VLCFA), patients with defects in plasmalogen
      synthesis are deficient in erythrocyte membrane plasmalogens, and patients with
      mislocalized pipecolic acid oxidase accumulate pipecolic acid in body fluids.
      This unit describes three protocols that can be used to measure plasma VLCFA,
      erythrocyte plasmalogens, and plasma or urine pipecolic acid by capillary gas
      chromatography (GC) or GC-mass spectrometry. These techniques can be used to
      identify the majority of patients with known neurogenetic peroxisome disorders.

PMID- 18633976
TI  - Oligonucleotide microarrays for clinical diagnosis of copy number variation.
AB  - Detection of genomic copy number variation is now considered the standard of care
      in the evaluation of children with developmental delay, and is used for other
      clinical indications such as multiple congenital anomalies and autism spectrum
      disorders. Fluorescence in situ hybridization (FISH) was the first molecular
      method for detection of submicroscopic genomic copy number variation, but
      microarray based comparative genomic hybridization (array CGH) offers several
      advantages as an adjunct to traditional cytogenetic methods such as karyotype and
      FISH. This unit focuses on oligonucleotide arrays, but includes background
      information on basic differences between oligonucleotide arrays and bacterial
      artificial chromosome (BAC) arrays. Array sensitivity is influenced by probe
      coverage or density, probe location, and choice of oligo array formats (i.e.,
      targeted versus whole genome). Array platform influences the likelihood of
      detecting variants of unknown significance. Clinical interpretation of such
      variants is discussed.

PMID- 18633977
TI  - Determination of carbon dioxide evolution rate using on-line gas analysis during
      dynamic biodegradation experiments.
AB  - Respirometry is a precious tool for determining the activity of microbial
      populations. The measurement of oxygen uptake rate is commonly used but cannot be
      applied in anoxic or anaerobic conditions or for insoluble substrate. Carbon
      dioxide production can be measured accurately by gas balance techniques,
      especially with an on-line infrared analyzer. Unfortunately, in dynamic systems,
      and hence in the case of short-term batch experiments, chemical and physical
      transfer limitations for carbon dioxide can be sufficient to make the observed
      carbon dioxide evolution rate (OCER) deduced from direct gas analysis very
      different from the biological carbon dioxide evolution rate (CER).To take these
      transfer phenomena into account and calculate the real CER, a mathematical model
      based on mass balance equations is proposed. In this work, the chemical
      equilibrium involving carbon dioxide and the measured pH evolution of the liquid
      medium are considered. The mass transfer from the liquid to the gas phase is
      described, and the response time of the analysis system is evaluated.Global mass
      transfer coefficients (K(L)a) for carbon dioxide and oxygen are determined and
      compared to one another, improving the choice of hydrodynamic hypotheses. The
      equations presented are found to give good predictions of the disturbance of
      gaseous responses during pH changes.Finally, the mathematical model developed
      associated with a laboratory-scale reactor, is used successfully to determine the
      CER in nonstationary conditions, during batch experiments performed with
      microorganisms coming from an activated sludge system.

PMID- 18633978
TI  - Identification of linearity in the biofilm process and its operational utility.
AB  - Various reported field studies on the performance of biofilm reactors suggest
      that the linear control of the system is effective for maintaining the consistent
      treatment efficiency under changing environmental conditions. However, no
      theoretical basis is available in the literature to substantiate such a claim. In
      this article, inherent linearity of the biofilm process has been identified along
      with the conditions under which this linearity exists. Exploiting the linear
      state of the system, operational criteria for regulating the performance of the
      biofilm reactors are obtained. The utility and applicability of the developed
      criteria are numerically demonstrated.

PMID- 18633979
TI  - Performance of a styrene-degrading biofilter containing the yeast Exophiala
      jeanselmei.
AB  - A general mathematical model developed for a description of pollutant degradation
      in a biofilm was used to evaluate the performance of a biofilter for the
      purification of styrene-containing gas. The biofilter contained perlite as an
      inert support on which a biofilm was present composed of a mixed microbial
      population containing the fungus Exophiala jeanselmei as a major styrene
      degrading microorganism. Although styrene is a moderately hydrophobic compound,
      the biofilter was reaction limited at a styrene gas phase concentration of 0.1
      2.4 g/m(3). Limitation of biofilter performance by the mass transfer of styrene
      was only observed at styrene concentrations lower than 0.06 g/m(3). A maximal
      styrene degradation rate of 62 g/(m(3). h) was maintained for over 1 year. At a
      high styrene concentration, the maximal styrene degradation rate could be
      increased to 91 g/(m(3). h) by increasing the oxygen concentration in the gas
      from 20 to 40%. After 300 days of operation, the dry-weight biomass concentration
      of the filter bed was 41% (w/w), and an average biofilm thickness of 240-280
      microm, but maximal up to 600 microm, was observed. Experimental results and
      model calculations indicated an effective biofilm thickness of about 80 microm.
      It is postulated that the thickness of the effective biofilm is determined by the
      oxygen availability in the biofilm.

PMID- 18633980
TI  - Development of a new reversed micelle liquid emulsion membrane for protein
      extraction.
AB  - A new type of liquid emulsion membrane containing reversed micelles for protein
      extraction is introduced. A three-step extraction mechanism is proposed including
      solubilization, transportation, and release of the protein. The surfactants
      Span80 and sodium di(2-ethylhexyl)sulfosuccinate (AOT) are used to stabilize the
      membrane phase and to build up the reversed micelles, respectively. alpha
      Chymotrypsin was used as the model protein. The condition in the internal phase
      inhibits the solubilization process of the already extracted protein back into
      reversed micelles. Concerning the solubilization, we studied the influence of the
      AOT concentration in the membrane phase and the ionic strength in the external
      phase. The extraction rate increases with higher AOT concentration and decreases
      with higher ionic strength. Using NaCl in the external phase led to better
      extraction results than using KCl. Maximum extraction results of 98% into the
      membrane phase and 65% into the internal phase were obtained. This condition
      retained 60% of the enzyme's activity. The concentration of KCl in the internal
      phase does not affect the solubilization rate but the release into the internal
      phase. By this way the ionic strength in the internal phase is used as the
      driving force for the protein release. The solubilization process is much faster
      than the diffusion and the releasing process, as found by variation of the
      extraction time. The influence of the operating conditions on the membrane
      swelling is also discussed.

PMID- 18633981
TI  - Analysis of secretory dynamics and development of media for the controlled
      secretion of insulin-related peptides from betaTC-3 insulinoma cells.
AB  - Controlled secretion of proteins from endocrine-derived cell lines has been
      proposed as a means to produce some classes of post-translationally modified
      proteins in bioreactors. Under the right biological and environmental conditions
      it may be possible to improve the product purity or quality relative to that
      obtained through steady (constitutive) secretion. The pancreatic-islet-derived
      cell line, betaTC-3, was selected as a model system to explore the secretory
      dynamics of insulin under various combinations of stimulatory or inhibitory
      environmental conditions. The betaTC-3 cells exhibited a glucose-mediated
      stimulus-response pattern which was saturated above 1 mM glucose and with an
      apparent "Kg" of 0.1 mM glucose. However, the kinetics of insulin synthesis were
      closely coupled to those of secretion such that betaTC-3 cells cycled between
      saturating and basal levels of glucose were never perturbed far from an
      intracellular synthesis-secretion equilibrium. When more powerful and selective
      agents were used to control secretion, the system performance improved markedly.
      A combination of 1 mM isobytylmethylxanthine (IBMX) and 1 microM carbachol (with
      saturating levels of glucose) could discharge 75% of stored insulin in 2 h. When
      this treatment was followed by incubation in media adjusted to attenuate the
      influx of calcium into the cells, intracellular pools were efficiently
      replenished within 24 h. Calcium attenuating treatments included
      hyperpolarization with reduced potassium (1 mM), calcium channel blockade with
      the dihydropyridine verapamil (1 microM), and the direct mass-action effect of
      reduced environmental calcium (0.5 mM versus 1.8 mM). Other inhibitory treatments
      were explored, but these tended to reduce both insulin synthesis and secretion.
      The best recharging treatment found was a combination of verapamil (1 microM)
      with reduced calcium level (0.5 mM).To demonstrate the feasibility of a
      controlled secretion process, betaTC-3 T-flask cultures were grown to confluence,
      then cycled through two periods of discharging (2 h) and recharging (20 h) with
      the best combinations of secretagogues and calcium attenuators. The overall
      process was quite efficient: Only 15% of the overall insulin secretion took place
      during the recharging episodes, and this residual secretion represented only 10%
      of the net insulin synthesis during these episodes. Discharging was very
      effective in the first episode (80% recovery of stored insulin), but slightly
      less efficient in subsequent discharging episodes, possibly due to a
      desensitization effect of the calcium attenuating media. Nevertheless, the
      regulated secretory pathway of betaTC-3 cells could be successfully harnessed to
      a controlled secretion process for the selective recovery of stored insulin.

PMID- 18633982
TI  - Processing and secretion of insulin-related peptides in an insulinoma cell line.
AB  - Certain classes of prohormones and other neuroendocrine or endocrine-derived
      secretory proteins are post-translationally modified in the secretory storage
      granules. If such molecules were to be biosynthesized to acceptable quantity and
      yield using endocrine-derived cell lines, it would be important to understand the
      relationship between the secretory dynamics and the conversion and release of the
      immature and mature forms of the molecule. We studied aspects of such a
      relationship using the endocrine-derived cell line betaTC-3, which synthesizes
      murine proinsulin, sequesters it into secretory granules, and converts it into
      mature insulin. In T-flask experiments with confluent cultures of betaTC-3 cells,
      intracellular and secreted (pro)insulin was sampled before and after episodes of
      stimulated exocytosis and recharging and quantified by radioimmunoassay and
      reversed-phase high-performance liquid chromatography (HPLC). Under conditions of
      steady-state secretion in glucose-rich growth medium the cells turned over their
      (pro)insulin inventory (90 +/- 5% mature insulin) at 2-3% per hour through
      secretion of (pro)insulin which was less than 70% mature. During an episode of
      hyperstimulated exocytosis induced by the combined secretagogues carbachol (1
      microM) and isobutylmethylxanthine (1 mM), approximately 80% of the intracellular
      (pro)insulin stores were depleted within 2 h and 84 +/- 4% of the secreted
      (pro)insulin was in the mature form. Following the discharging episode,
      exocytosis was suppressed to 10% of its steady-state rate with a treatment which
      attenuated calcium influx (20 microM verapamil with reduced levels of calcium in
      the medium). Under this condition the secreted protein was only approximately 50%
      converted to mature insulin, but 85 +/- 10% of the net (pro)insulin accumulating
      within the intracellular stores was converted to the mature form. The inverse
      relationship between rate of secretion and degree of conversion of secreted
      (pro)insulin is consistent with a previously observed phenomenon of preferential
      basal secretion from immature secretory granules. This tends to enrich the
      secreted peptides in immature forms relative to the total intracellular pool.
      Preferential early secretion can best be overcome by rapid discharging of the
      long-term and predominantly mature stores. Thus, a cyclic controlled secretion
      process wherein product is collected during intermittent discharging episodes
      would provide a better yield of mature product than would steady-state secretion.

PMID- 18633983
TI  - Monte Carlo simulation of the enzymatic lysis of yeast.
AB  - The overall reaction in the enzymatic lysis of yeast takes place in three major
      steps: (i) the two-layer wall is digested, (ii) the cell bursts under the osmotic
      pressure difference to release its intracellular material, and (iii) the
      intracellular material is digested by the enzymes still present in the solution.
      The first and third steps are continuous processes, adequately described by
      Michaelis-Menten kinetic models. The second step is a discrete event, statistical
      in nature. A model of engineering value should effectively bridge the gap between
      the two continuous processes (first and third steps). In this work, Monte Carlo
      simulations are used to identify a suitable function that captures the
      statistical nature of cell rupture and represents the rate of release of
      intracellular material. It is shown that the two-parameter beta distribution
      function serves this purpose most effectively. Comparisons with experimental
      results indicate that the cell rupture ratio is a widely distributed statistical
      function.

PMID- 18633984
TI  - Microbial ecosystems in compost and granular activated carbon biofilters.
AB  - Compost and granular activated carbon biofilters operated at a wastewater
      treatment plant simultaneously removed low concentrations of hydrogen sulfide and
      volatile organic compounds. Through the use of phospholipid fatty acid analyses,
      the effects of declining pH caused by sulfide oxidation were established for
      microbial growth, microorganism stress, and microbial community structure.
      Microorganisms on both media demonstrated increases in microbial densities,
      varying degrees of environmental stress, and domination by gram-negative
      bacteria. However, the declining pH had little effect on compound removal, which
      was greater than 99% for the hydrogen sulfide and greater than 70% for the
      oxygenated and aromatic hydrocarbons. The microbial communities adjusted to
      difficult environmental conditions through acclimation of the species present or
      by growth of low-pH-tolerant species.

PMID- 18633985
TI  - Phosphate uptake kinetics by Acinetobacter isolates.
AB  - Acinetobacter isolates from activated sludge treatment plants of forest industry
      were used as model organisms for polyphosphate accumulating bacteria to study
      excess phosphate uptake by the overplus phenomenon as well as luxury uptake of
      phosphate during growth. The initial, rapid phosphate uptake by the phosphorus
      starved Acinetobacter isolates (the overplus phenomenon) followed the Michaelis
      Menten model (maximum initial phosphate uptake rate 29 mg P g(-1) dry mass (DM)
      h(-1), half-saturation constant for excess phosphate uptake 17 mg P L(-1)).
      During the rapid uptake no growth was observed, but most cells contained
      polyphosphate granules. Also growth and luxury uptake of phosphate could be
      modeled with the Michaelis-Menten equation (maximum phosphate uptake rate 3.7-12
      mg P g(-1) DM h(-1), half-saturation constant for growth 0.47-6.0 mg P L(-1),
      maximum specific growth rate 0.15-0.55 h(-1)).

PMID- 18633986
TI  - A structured model for Thiobacillus ferrooxidans growth on ferrous iron.
AB  - A structured model for Thiobacillus ferrooxidans growth dependence on ferrous and
      ferric iron, arsenic, oxygen, carbon dioxide, pH, and temperature is presented. A
      new kinetic mechanism for ferrous oxidation by T. ferrooxidans is introduced.
      Data from several earlier experimental studies of T. ferroaxidans growth are used
      for model development.

PMID- 18633987
TI  - Numerical modeling and uncertainties in rate coefficients for methane utilization
      and TCE cometabolism by a methane-oxidizing mixed culture.
AB  - The rates of methane utilization and trichloroethylene (TCE) cometabolism by a
      methanotrophic mixed culture were characterized in batch and pseudo-steady-state
      studies. Procedures for determination of the rate coefficients and their
      uncertainties by fitting a numerical model to experimental data are described.
      The model consisted of a system of differential equations for the rates of Monod
      kinetics, cell growth on methane and inactivation due to TCE transformation
      product toxicity, gas/liquid mass transfer of methane and TCE, and the rate of
      passive losses of TCE. The maximum specific rate of methane utilization (k(CH(4)
      )) was determined by fitting the numerical model to batch experimental data, with
      the initial concentration of active methane-oxidizing cells (X(0) (a)) also used
      as a model fitting parameter. The best estimate of k(CH(4) ) was 2.2 g CH(4)/g
      cells-d with excess copper available, with a single-parameter 95% confidence
      interval of 2.0-2.4 mg/mg-d. The joint 95% confidence region for k(CH(4) ) and
      X(0) (a) is presented graphically. The half-velocity coefficient (K(S,CH(4) ))
      was 0.07 mg CH(4)/L with excess copper available and 0.47 mg CH(4)/L under copper
      limitation, with 95% confidence intervals of 0.02-0.11 and 0.35-0.59 mg/L,
      respectively. Unique values of the TCE rate coefficients k(TCE) and K(S,TCE)
      could not be determined because they were found to be highly correlated in the
      model fitting analysis. However, the ratio k(TCE)/K(S,TCE) and the TCE
      transformation capacity (T(C)) were well defined, with values of 0.35 L/mg-day
      and 0.21 g TCE/g active cells, respectively, for cells transforming TCE in the
      absence of methane or supplemental formate. The single-parameter 95% confidence
      intervals for k(TCE)/K(S,TCE) and T(C) were 0.27-0.43 L/mg-d and 0.18-0.24 g
      TCE/g active cells, respectively. The joint 95% confidence regions for
      k(TCE)/K(S,TCE) and T(C) are presented graphically.

PMID- 18633988
TI  - Production and characterization of a plant alpha-hydroxynitrile lyase in
      Escherichia coli.
AB  - The coding sequence of the cyanogenic alpha-hydroxynitrile lyase gene of Manihot
      esculenta Crantz (cassava) was cloned in the plasmid vector pMal-c2 and expressed
      in Escherichia coli strain JM105. DNA sequencing showed that the recombinant
      plasmid contained the same sequence as the cDNA clone pHNL10. Peptide sequencing
      of the recombinant protein showed that the N-terminus was heterogeneous, with
      either four or six additional amino acid residues compared with the native
      protein. Circular dichroism spectra indicated similar secondary structure
      contents for both proteins. Enzyme assays showed that specific activity of native
      and recombinant proteins were 0.24 and 0.26 mmol CN(-)/mg/min, respectively; that
      both proteins had optimal activity at 40 degrees C and pH 5.5; and that both
      proteins were inhibited by the serine protease inhibitor phenyl-methane sulfonyl
      flouride (PMSF). Isoelectric focusing of native and recombinant protein revealed
      multiple isoforms for both proteins; the recombinant protein had a more basic
      mean isoelectric point (pl) (5.1) than the native protein (4.5).

PMID- 18633989
TI  - Regulation of growth and adhesion of cultured cells by insulin conjugated with
      thermoresponsive polymers.
AB  - We developed a new biomaterial for use in cell culture. The biomaterial enabled
      protein-free cell culture and the recovery of viable cells by lowering the
      temperature without the aid of supplements. Insulin was immobilized and a
      thermoresponsive polymer was grafted onto a substrate. We investigated the effect
      of insulin coupling on the lower critical solution temperature (LCST) of the
      thermoresponsive polymer, poly(N-isopropylacrylamide-co-acrylic acid), using
      polymers that were ungrafted, or coupled with insulin. The insulin conjugates
      were precipitated from an aqueous solution at high temperatures, but they were
      soluble at low temperatures. The LCST was not significantly affected by the
      insulin coupling. The thermoresponsive polymer was grafted to glow-discharged
      polystyrene film and covalently conjugated with insulin. The surface wettability
      of the conjugate film was high at low temperatures and low at high temperatures.
      The amounts of immobilized insulin required to stimulate cell growth were 1-10%
      of the amount of free insulin required to produce the same effect. The maximal
      mitogenic effect of immobilized insulin was greater than that of free insulin.
      About half of the viable cells was detached from the film only by lowering the
      temperature. The recovered cells proliferated normally on new culture dishes.

PMID- 18633990
TI  - On the pH memory of lyophilized compounds containing protein functional groups.
AB  - Lyophilized proteins exhibit "pH memory," i.e., their behavior in the solid form
      corresponds to the pH of the aqueous solution from which they were freeze dried.
      Herein, we directly tested whether the ionization state is "remembered" by model
      organic compounds containing various protein functional groups (amino, carboxyl,
      and phenolic). The fraction of ionized species was quantitated from the infrared
      spectra of both the aqueous and lyophilized states. The pK(a) values in the
      aqueous and lyophilized forms for each compound were found to be quite similar,
      within 0.3 units from each other.

PMID- 18633991
TI  - Immunoblotting and immunodetection.
AB  - Immunoblotting (western blotting) is used to identify specific antigens
      recognized by polyclonal or monoclonal antibodies. This unit provides protocols
      for all steps, starting with solubilization of the protein samples, usually by
      means of SDS and reducing agents. Following solubilization, the material is
      separated by SDS-PAGE and the antigens are electrophoretically transferred to a
      membrane, a process that can be monitored by reversible staining with Ponceau S.
      The transferred proteins are bound to the surface of the membrane, providing
      access to immunodetection reagents. After nonspecific binding sites are blocked,
      the membrane is probed with the primary antibody and washed. The antibody-antigen
      complexes are tagged with horseradish peroxidase or alkaline phosphatase coupled
      to a secondary anti-IgG antibody, and detected using appropriate chromogenic or
      luminescent substrates. Finally, membranes may be stripped and reprobed.

PMID- 18633992
TI  - Production of monoclonal antibody supernatant and ascites fluid.
AB  - This unit details methods for production of monoclonal antibodies. Two methods
      are given for production of hybridoma supernatants, including one for large-scale
      production. A protocol for large-scale production of hybridomas or cell lines is
      presented for use in isolation of cellular proteins. Finally, a method is given
      for producing and obtaining mouse ascites fluid containing monoclonal antibody.
      Recommendations developed by the Committee on Methods of Producing Monoclonal
      Antibodies (Institute of Laboratory Animal Research, National Research Council)
      on the use of animals for producing monoclonal antibodies are also discussed.
      These recommendations are designed to foster the judicious use of animals and to
      strongly encourage the use of in vitro methods whenever possible.

PMID- 18633993
TI  - Using Morpholinos to control gene expression.
AB  - Morpholino oligonucleotides are stable, uncharged, water-soluble molecules that
      bind to complementary sequences of RNA, thereby inhibiting mRNA processing, read
      through, and protein binding at those sites. Morpholinos are typically used to
      inhibit translation of mRNA, splicing of pre-mRNA, and maturation of miRNA,
      although they can also inhibit other interactions between biological
      macromolecules and RNA. Morpholinos are effective, specific, and lack non
      antisense effects. They work in any cell that transcribes and translates RNA.
      However, unmodified Morpholinos do not pass well through plasma membranes and
      must therefore be delivered into the nuclear or cytosolic compartment to be
      effective. Morpholinos form stable base pairs with complementary nucleic acid
      sequences but apparently do not bind to proteins to a significant extent. They
      are not recognized by proteins and do not undergo protein-mediated catalysis; nor
      do they mediate RNA cleavage by RNase H or the RISC complex. This work focuses on
      techniques and background for using Morpholinos.

PMID- 18633994
TI  - The all-too-flexible abductive method: ATOM's normative status.
AB  - The author discusses the abductive theory of method (ATOM) by Brian Haig from a
      philosophical perspective, connecting his theory with a number of issues and
      trends in contemporary philosophy of science. It is argued that as it stands, the
      methodology presented by Haig is too permissive. Both the use of analogical
      reasoning and the application of exploratory factor analysis leave us with too
      many candidate theories to choose from, and explanatory coherence cannot be
      expected to save the day. The author ends with some suggestions to remedy the
      permissiveness and lack of normative force in ATOM, deriving from the
      experimental practice within which psychological data are produced.

PMID- 18633995
TI  - Extracorporeal photopheresis improves nephrogenic fibrosing
      dermopathy/nephrogenic systemic fibrosis: three case reports and review of
      literature.
AB  - Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a
      recently recognized systemic fibrosing disorder that develops in the context of
      renal insufficiency. Its predominant manifestation is severe cutaneous fibrosis,
      often causing disabling contractures of neighboring joints. No therapy is
      consistently effective, and etiology and pathogenesis remain obscure. However,
      gadolinium-containing contrast agents used in magnetic resonance imaging or
      angiography have recently been strongly linked to the development of fibrosis in
      NSF. We report a clinical response to treatment with extracorporeal photopheresis
      (ECP) using the Therakos UVAR XTS system in three cases of NFD/NSF associated
      with flexion contractures affecting all four limbs. All three patients were
      receiving renal replacement therapy for longstanding end-stage renal failure. All
      three showed clinical response with softening of skin plaques at the end of four
      cycles, and improved range of movement in all four limbs on completion of
      treatment. The first patient, with NFD/NSF of 4.5 year's duration, was able to
      resume most activities of daily living although still chairbound, while a second
      patient with more recent onset of NSF was able to walk short distances with the
      help of Zimmer frames by the end of 16-18 cycles of treatment, having been
      chairbound pretreatment. A third patient with milder initial symptoms also
      experienced significant improvement after a shorter course of ECP treatment. Our
      experience with these three patients confirms previous case reports, suggesting
      that ECP may be effective in NFD/NSF.

PMID- 18633996
TI  - Postpartum plasma exchange as adjunctive therapy for severe acute fatty liver of
      pregnancy.
AB  - Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic
      insufficiency and secondary systemic compromise that poses significant fetal
      maternal risk. Plasma exchange (PEX) is an effective bridge therapy to sustain
      liver function and enable hepatocellular regeneration to occur in nonpregnant
      patients following acute decompensation of a chronic liver disease or while
      awaiting liver transplantation. The application of PEX for patients with AFLP is
      a novel concept; since 1988 we have utilized postpartum PEX (PPEX) as adjunctive
      medical therapy for six patients with severe AFLP. Before PPEX initiation, four
      patients had signs and symptoms of encephalopathy, three required ventilatory
      support, five had advanced liver insufficiency, and all six were developing renal
      failure. PPEX was initiated 2-8 days following delivery and repeated (two to four
      times, mean = 3) at 24-48-h intervals thereafter. All patients responded with
      composite clinical (symptoms/signs) and laboratory improvement; the average
      length of hospitalization following final PPEX for five of six patients was 7
      days. No significant PPEX-related complications occurred. PPEX utilization in
      patients with severe AFLP may enhance maternal recovery by preventing secondary
      sequelae from hepatic insufficiency until spontaneous healing can occur. Further
      study appears to be indicated to validate a role for PPEX as supportive therapy
      for puerperal patients with AFLP suffering multiorgan failure.

PMID- 18633997
TI  - Culture of postnatal mesencephalic dopamine neurons on an astrocyte monolayer.
AB  - This unit presents a protocol for primary culture of postnatal mesencephalic
      dopamine neurons grown on an astrocyte monolayer, which can be used to
      investigate cellular and molecular mechanisms regulating dopamine neuron
      function. Using this in vitro approach, dopamine neurons survive for an extended
      period of time and establish functional axon terminals and dendrites that display
      properties similar to those observed in vivo and in brain slices. An alternate
      protocol is provided for a microculture system in which astrocytes are grown on a
      spatially limited surface where single or small groups of dopamine neurons
      develop. Under such conditions, isolated neurons establish synaptic contacts, or
      autapses, onto their own somatodendritic compartment, thus facilitating
      morphological and physiological experiments.

PMID- 18633998
TI  - Conditional gene expression and targeting in neuroscience research.
AB  - Recently developed techniques for spatially and temporally controlled genetic
      manipulations based on regulated homologous recombination and/or transcription
      are extensively used in brain research. In addition to being important for
      testing the role of specific proteins in the central nervous system, these
      techniques allow analysis of brain functions at the neuronal circuit level. This
      overview discusses principles of conditional inactivation and expression of
      genes, and their specific applications to studies of the mammalian brain.

PMID- 18633999
TI  - Assessment of cell viability in primary neuronal cultures.
AB  - This unit contains five protocols for assaying cell viability in vitro using
      primary neuronal cultures, including a novel method for use with transfected
      neurons. Three of the assays are based on the principle that cell death cascades
      alter membrane permeability. The lactate dehydrogenase (LDH) release assay
      measures the amount of the cytoplasmic enzyme released into the bathing medium,
      while the trypan blue and propidium iodide assays measure the ability of cells to
      exclude dye from their cytoplasm. The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay measures the mitochondrial activity of
      viable cells by quantifying the conversion of the tetrazolium salt to its
      formazan product. Finally, the fifth assay details the measurement of luciferase
      expression as an indication of neuronal viability within a relatively small
      population of transfected neurons.

PMID- 18634000
TI  - The Majchrowicz binge alcohol protocol: an intubation technique to study alcohol
      dependence in rats.
AB  - Binge drinking of alcohol is an important public health issue, and experimental
      studies are needed to understand the pathophysiological mechanisms of this
      problem and develop improved approaches to treatment. This unit presents a
      validated and widely used method to model binge alcohol drinking in rats. It
      consists of three daily intragastric administrations of ethanol to rats for 4
      days. Ethanol is initially administered at 5 g/kg, and then each subsequent dose
      is determined based on the degree of intoxication the rat exhibits prior to each
      dose. The behavior of the animal is graded based on a well-described scale. After
      the fourth day, various aspects of the ethanol withdrawal syndrome can be
      observed over a predictable time course and additional protocols can be employed
      to study mechanisms of specific aspects of withdrawal and treatments to prevent
      them. One specific behavior observed during ethanol withdrawal and described here
      is sound-induced (audiogenic) convulsive seizure.

PMID- 18634001
TI  - Vapor inhalation of alcohol in rats.
AB  - Alcohol dependence constitutes a neuroadaptive state critical for understanding
      alcoholism, and various methods have been utilized to induce alcohol dependence
      in animals, one of which is alcohol vapor exposure. Alcohol vapor inhalation
      provides certain advantages over other chronic alcohol exposure procedures that
      share the ultimate goal of producing alcohol dependence in rats. Chronic alcohol
      vapor inhalation allows the experimenter to control the dose, duration, and
      pattern of alcohol exposure. Also, this procedure facilitates testing of somatic
      and motivational aspects of alcohol dependence. Chronic exposure to alcohol vapor
      produces increases in alcohol-drinking behavior, increases in anxiety-like
      behavior, and reward deficits in rats. Alcohol vapor inhalation as a laboratory
      protocol is flexible, and the parameters of this procedure can be adjusted to
      accommodate the specific aims of different experiments. This unit describes the
      options available to investigators using this procedure for dependence induction,
      when different options are more or less appropriate, and the implications of
      each.

PMID- 18634003
TI  - Delayed death of identified reticulospinal neurons after spinal cord injury in
      lampreys.
AB  - There is controversy about whether axotomized neurons undergo death or only
      severe atrophy after spinal cord injury (SCI) in mammals. Lampreys recover from
      complete spinal transection, but only about half of the severed spinal-projecting
      axons regenerate through the site of injury. The fates of the unregenerated
      neurons remain unknown, and until now death of axotomized spinal-projecting
      neurons has not been described in the lamprey brain. We now report that in
      animals allowed to survive for 12 or more weeks after spinal cord transection,
      several identified reticulospinal (RS) neurons were missing in Nissl-stained or
      neurofilament-immunostained brain whole mounts. At earlier times, these neurons
      were swollen and pale in Nissl-stained preparations. Retrograde fluorescent
      labeling from the site of transection combined with TUNEL histochemistry
      suggested that neuronal death, including that of the identified RS neurons, began
      in animals 4 weeks posttransection, reaching a peak at 12-16 weeks. This was not
      seen in untransected animals. The TUNEL positivity suggests that some cells were
      dying by apoptosis. Of special interest, among the identified neurons, this
      delayed cell death was restricted to neurons that at earlier posttransection
      times have a low probability of regeneration. These data show that SCI induces
      delayed cell death in lamprey spinal-projecting neurons and suggest that the
      reason why some neurons are "bad regenerators" is that they are already
      undergoing apoptotic cell death. Thus protection from apoptosis may be necessary
      in order to enhance axonal regeneration after SCI.

PMID- 18634002
TI  - Connections and synaptic function in the posteroventral cochlear nucleus of deaf
      jerker mice.
AB  - Mutations in the gene that encodes espins can cause deafness and vestibular
      disorders; mice that are homozygous for the autosomal recessive jerker mutation
      in the espin gene never hear. Extracellular injections of biocytin into the
      anteroventral cochlear nucleus (AVCN) revealed that although the cochlear nuclei
      are smaller in je/je mice, the topography in its innervation resembles that in
      wild-type mice. Auditory nerve fibers innervate narrow, topographically
      organized, "isofrequency" bands in deaf animals over the ages examined, P18-P70.
      The projection of tuberculoventral cells was topographic in je/je as in wild-type
      mice. Terminals of auditory nerve fibers in the multipolar cell area included
      both large and small endings, whereas in the octopus cell area they were
      exclusively small boutons in je/je as in wild-type mice, but end bulbs near the
      nerve root of je/je animals were smaller than in hearing animals. In whole-cell
      recordings from targets of auditory nerve fibers, octopus and T stellate cells,
      miniature excitatory postsynaptic currents (mEPSCs) had similar shapes as in +/+,
      indicating that the properties of AMPA receptors were not affected by the
      mutation. In je/je animals the frequency of spontaneous mEPSCs was elevated, and
      synaptic depression in responses to trains of shocks delivered at between 100 and
      333 Hz was greater than in wild-type mice, indicating that the probability of
      neurotransmitter release was increased. The frequency of spontaneous mEPSCs and
      extent of synaptic depression were greater in octopus than in T stellate cells,
      in both wild-type and in je/je mice.

PMID- 18634004
TI  - Anatomical and functional characterization of neuropil in the gracile fasciculus.
AB  - A fundamental organizational principle of the central nervous system is that gray
      matter is the province of neuronal somata, white matter their processes. However,
      the rat and primate dorsal columns (archetypal spinal "white matter" tracts) are
      actually of intermediate character, insofar as they contain a surprisingly
      prominent neuropil of unknown function. Here I report on the morphology, inputs,
      projections, and functional properties of these neurons. Small fusiform and
      larger lentiform neurons are most abundant in the gracile fasciculus of the
      cervical and lumbar enlargements and are absent from the cuneate fasciculus and
      corticospinal tract. Many have dendrites that run along the dorsal pia, and,
      although in transverse sections these neurons appear isolated from the gray
      matter, they are also connected to area X by varicose and sometimes loosely
      fasciculated dendrites. These neurons receive neurochemically diverse,
      compartmentalized synaptic inputs (primary afferent, intrinsic and descending),
      half express the substance P receptor, and some project supraspinally. Unlike
      substantia gelatinosa neurons, they do not express protein kinase C gamma.
      Functionally, they have small receptive fields, which are somatotopically
      appropriate with respect to their anterior-posterior position along the neuraxis.
      They respond to innocuous and/or noxious mechanical stimulation of the distal
      extremities, and some are prone to central sensitization or "windup."
      Morphologically, neurochemically, and functionally, therefore, these cells most
      closely resemble neurons in laminae III-VI in the dorsal horn. The proximity of
      their dorsal dendrites to the pia mater may also reflect an ability to integrate
      internal (e.g., changes in cerebrospinal fluid compostition) and external (e.g.,
      somatic) stimuli.

PMID- 18634005
TI  - The impact of colony-stimulating factor-1 on fracture healing: an experimental
      study.
AB  - The role of colony stimulating factor-1 (CSF-1) in the regulation of osteoclasts
      and bone remodeling suggests that CSF-1 may also be involved in regulation of
      bone healing. The ability of CSF-1 to promote healing of bone defects was tested
      in a rabbit model. Twenty-four New Zeeland rabbits were included in the study.
      Animals were assigned to two groups: the control group (n = 12) was treated by
      plate fixation. The animals in the second group (n = 12) were also stabilized by
      conventional plating and received additionally CSF-1 for 2 weeks systemically.
      Histologic, histomorphometric, and radiologic examinations were performed to
      evaluate the healing process at 4, 8, and 12 weeks following surgery. Animals
      that were treated by CSF-1 produced a significantly higher amount of mineralized
      bone over the first 8 weeks after fracture compared to the control animals.
      Furthermore, a higher number of osteoclasts was found in CSF-1-treated animals
      within the first 8 weeks, compared to the controls. The present data emphasize
      for the first time the importance of CSF-1 in the bone healing. The use of CSF-1
      in addition to conventional fixation might be a novel approach for the treatment
      of bone defects.

PMID- 18634006
TI  - Autologous nucleus pulposus primes T cells to develop into interleukin-4
      producing effector cells: an experimental study on the autoimmune properties of
      nucleus pulposus.
AB  - An autoimmune response to herniated nucleus pulposus has been proposed to
      constitute a pathophysiologic mechanism for inducing sciatica based on the fact
      that nucleus pulposus under normal conditions is excluded from the development of
      immunological tolerance. The manifestation of an autoimmune response comprises
      different steps starting with antigen capture, continuing with activation of T
      helper (T(H)) cells and ending with production of autoantibodies. Activated T(H)
      cells differentiate into either T(H)1 cells, predominately producing
      proinflammatory cytokines such as interferon gamma (IFNgamma) or a T(H)2 subset
      mainly producing anti-inflammatory cytokines such as interleukin-4 (IL-4). The
      aim of the present study was to examine if exposure of autologous nucleus
      pulposus (NP) to the immune system for 3 weeks is potent enough to prime T(H)
      cells to differentiate into T(H)2 cells. The study was performed in a pig model
      allowing the exposure of NP to the immune system. To assess the polarization of
      T(H) cells the intracellular production of IFNgamma and IL-4 was measured in T
      cells by using flow cytometry. The revealed predominant production of IL-4
      together with low production of IFNgamma in T cells after NP exposure to the
      immune system indicates that nucleus pulposus may prime T(H) cells to develop
      into IL-4-producing T(H)2 cells after being exposed to the immune system, for
      example, in association with disc herniation.

PMID- 18634007
TI  - The association between velocity of the center of closest proximity on
      subchondral bones and osteoarthritis progression.
AB  - Altered surface interactions following joint instability may apply novel,
      damaging loads to articular cartilage. This study measured the velocity of the
      centers of closest proximity on subchondral bone surfaces on the femur and tibia
      during running in normal and unstable canine stifle (knee) joints. The purpose
      was to explore the relationship between the velocity of the centers of closest
      proximity on subchondral bones and the severity of cartilage damage. Dynamic
      biplane radiography was used to acquire serial knee kinematics [5 control, 18
      cranial cruciate ligament (CCL) deficient] during treadmill running over 2 years.
      Custom software calculated the difference between the rate at which the center of
      closest proximity on the femur translated relative to the femur bone surface and
      the rate at which the center of closest proximity on the tibia translated
      relative to the tibia bone surface. Comparisons were made between dogs that
      developed minor versus major medial compartment cartilage damage over 2 years.
      Major damage dogs showed a significantly greater increase in the difference
      between femur and tibia medial compartment closest proximity point velocity from
      the instant of paw strike to peak velocity difference at 2, 4, and 6 months after
      CCL transaction. This implies increased tangential forces associated with the
      velocity of the compressed cartilage region during joint movement (plowing) may
      be a mechanism that initiates osteoarthritis (OA) development and drives OA
      progression. In the future, articulating surface velocity measurements may be
      useful to identify patients at risk for long-term OA due to joint instability.

PMID- 18634008
TI  - Cartilage damage caused by metal implants applied for the treatment of
      established localized cartilage defects in a rabbit model.
AB  - The purpose of the current study was to investigate the feasibility of the
      application of defect-size femoral implants in a rabbit model of established
      cartilage defects and compare this treatment to microfracturing. In 31 New
      Zealand White rabbits, a medial femoral condyle defect was created in each knee.
      After 4 weeks, 3 animals were killed for defect baseline values. In the other 28
      rabbits, knees were sham-operated, treated with microfracturing, or treated by
      placing an oxidized zirconium (OxZr) or cobalt-chromium (CoCr) implant (theta
      articulating surface 3.5 mm; fixating pin of 9.1 mm length). These animals were
      sacrificed 4 weeks after treatment. Joints were evaluated macroscopically.
      Implant osseointegration was measured by automated histomorphometry, and
      cartilage repair was scored microscopically. Cartilage quality was analyzed
      macroscopically and microscopically. Bone-implant contact was 63.2% +/- 3.2% for
      CoCr and 62.5% +/- 3.2% for OxZr. Cartilage defects did not show complete
      healing, nor during subsequent sham-surgery or microfracturing. For all
      treatments, considerable cartilage damage in the articulating medial tibia, and
      degeneration of lateral tibial and femoral cartilage was observed (p < 0.05).
      Both CoCr and OxZr implant-treated defects showed an increase of cartilage
      degeneration compared to microfracturing and sham-operated defects (p < 0.05).
      Although only a single short-term follow-up period was investigated in this
      study, caution is warranted using small metal implants as a treatment for
      established localized cartilage defects because, even after 4 weeks in this
      model, the metal implants caused considerable degeneration of the articulating
      surface.

PMID- 18634010
TI  - Quantitative motion analysis in patients with hallux rigidus before and after
      cheilectomy.
AB  - The purpose of this study was to quantify changes in temporal-spatial parameters
      and multisegmental foot/ankle kinematics in a group of patients with hallux
      rigidus following cheilectomy. Three-dimensional motion analysis was conducted
      using a 15-camera Vicon Motion Analysis System on a population of 19 patients who
      underwent cheilectomy for hallux rigidus. Data were analyzed using the four
      segment Milwaukee Foot Model. Preoperative and postoperative tests were compared
      using paired parametric methods. Results showed significant improvements in
      walking speed, cadence, stride length, and stance/swing ratio from preoperative
      to postoperative state. Altered hallux and forefoot positions preoperatively
      showed shifts towards normal after cheilectomy. Although clinical improvements in
      pain and passive range of motion were statistically significant, similar
      improvements in range of motion were not demonstrated during ambulatory testing.
      The results of this study provide insight into ambulatory improvements following
      cheilectomy, and suggest further study of the rehabilitation process to improve
      the recovery of functional range of motion.

PMID- 18634009
TI  - Controlled release of GDNF reduces nerve root-mediated behavioral
      hypersensitivity.
AB  - Nerve root compression produces persistent behavioral sensitivity in models of
      painful neck injury. This study utilized degradable poly(ethylene glycol)
      hydrogels to deliver glial cell line-derived neurotrophic factor (GDNF) to an
      injured nerve root. Hydrogels delivered approximately 98% of encapsulated GDNF
      over 7 days in an in vitro release assay without the presence of neurons and
      produced enhanced outgrowth of processes in cortical neural cell primary
      cultures. The efficacy of a GDNF hydrogel placed on the root immediately after
      injury was assessed in a rat pain model of C7 dorsal root compression. Control
      groups included painful injury followed by: (1) vehicle hydrogel treatment (no
      GDNF), (2) a bolus injection of GDNF, or (3) no treatment. After injury,
      mechanical allodynia (n = 6/group) was significantly decreased with GDNF
      delivered by the hydrogel compared to the three injury control groups (p < 0.03).
      The bolus GDNF treatment did not reduce allodynia at any time point. The GDNF
      receptor (GFRalpha-1) decreased in small, nociceptive neurons of the affected
      dorsal root ganglion, suggesting a decrease in receptor expression following
      injury. GDNF receptor immunoreactivity was significantly greater in these neurons
      following GDNF hydrogel treatment relative to GDNF bolus treated and untreated
      rats (p < 0.05). These data suggest efficacy for degradable hydrogel delivery of
      GDNF and support this treatment approach for nerve root-mediated pain.

PMID- 18634011
TI  - Early dynamization by reduced fixation stiffness does not improve fracture
      healing in a rat femoral osteotomy model.
AB  - Dynamization of fracture fixation is used clinically to improve the bone healing
      process. However, the effect of early dynamization remains controversial. This
      study evaluated the effect of early dynamization, by reduced stiffness of
      fixation on callus stiffness and size after 5 weeks of healing in a rat
      diaphyseal femoral osteotomy. An external unilateral fixator allowed either a
      rigid (R-group; n = 8) or a flexible (F-group; n = 8) fixation. The dynamized
      group (D-group: n = 8) had a rigid fixation for 1 week, and then a flexible
      fixation for the remaining 4 weeks. The pre- and postoperative activity of the
      rats was measured. After 5 weeks, the rats were sacrificed, and healing was
      evaluated by biomechanical and densitometric methods. The R-group had a higher
      activity more closely approaching preoperative levels, compared to the D-group
      throughout all time points measured. This difference was significant after 14
      days and 21 days. The flexural rigidity of the R-group was 82% (tested in the
      anterior-posterior direction; p = 0.01) and 93% (tested in the medial-lateral
      direction; p = 0.002) greater than the flexural rigidity of the D-group. The
      rigid fixation led to a stiffer callus with a smaller callus volume, but better
      mineralized tissue in the whole callus and at the level of the osteotomy gap than
      the flexible or the dynamized fixation. Early dynamization did not improve
      healing compared to rigid or flexible fixation in a rat femoral osteotomy model.

PMID- 18634012
TI  - Proximal gait adaptations in medial knee OA.
AB  - The purpose of this study was to examine interlimb differences in gait kinematics
      and kinetics in patients with symptomatic medial knee OA. The main objective was
      to identify hip joint movement strategies that might lower the knee adduction
      moment and also compensate for decreased knee flexion during weight acceptance.
      Gait analysis was performed on 32 patients with moderate medial compartment knee
      OA. Kinetic and kinematic data were calculated and side-to-side comparisons made.
      Radiographs were used to identify frontal plane alignment. No interlimb
      difference in the peak knee adduction moment was found (p = 0.512), whereas a
      greatly reduced hip adduction moment was seen on the involved side (p < 0.001)
      during the early part of stance. The involved limb flexed significantly less and
      hip and knee flexion moments were smaller compared to the uninvolved side. Gait
      adaptations involving a lateral sway of the trunk may successfully lead to
      relatively lower ipsilateral knee adduction moments, and would further be
      reflected by a lower adduction moment at the hip. Subjects did not compensate for
      less knee flexion by any dynamic means, and likely experience a resulting higher
      joint impact. These gait adaptations may have implications with respect to
      development of weakness of the ipsilateral hip musculature and progression of
      multiarticular OA.

PMID- 18634013
TI  - Prevention of NTDs with periconceptional multivitamin supplementation containing
      folic acid in China.
AB  - BACKGROUND: Maternal nutritional factors seem to contribute substantially to the
      complex etiologies of NTDs. Foremost among these factors is the periconceptional
      use of supplementation containing folic acid, which is associated with a
      reduction in the risk of women having NTD-affected pregnancies. This study was
      designed to observe the effectiveness of multivitamin supplementation containing
      folic acid in preventing NTDs in a Chinese population and to detect factors that
      would impact the effectiveness. METHODS: Through family planning networks, a
      population-based community intervention study was carried out in 18 counties of
      China. Participants were divided into an intervention (taking multivitamin) group
      and a control group, and were followed up according to periconceptional
      multivitamin supplementation (in general 6 mg) for 2 years. Women who had a
      pregnancy were followed up from 28 weeks gestation at least to pregnancy
      termination, and the outcome was recorded. The incidence rate of the two groups
      and the relative risks were calculated to evaluate the efficacy of the
      multivitamin supplement in preventing NTDs. RESULTS: During 2000 and 2002, all of
      the women having pregnancies with birth defects and women whose pregnancies were
      without any birth defects were interviewed. Nine NTDs were recorded from 25,444
      pregnancies (NTD birth prevalence = 0.35/1,000 pregnancies) in the intervention
      group and 48 NTDs among 26,599 pregnancies (NTD birth prevalence = 1.80/1,000
      pregnancies) in the control group. The protective rate was 80.4%. CONCLUSIONS:
      Periconceptional multivitamin supplementation containing folic acid can prevent
      the occurrence of NTDs with the beneficial effect dependent on the frequency and
      timing of the supplementation. Our study suggests that multivitamin supplement
      containing folic acid taken from a time point of 2 months before conception and
      continuing until completion of the second month after conception and taken more
      than five times per week can significantly reduce the risks of NTDs.

PMID- 18634014
TI  - A rat model for evaluating physiological responses to femoral shaft fracture
      reduction using a surgical robot.
AB  - The first step in treatment of displaced femoral shaft fractures is adequate
      reduction of the fracture fragments. Manually performed, reduction can be
      challenging, and is frequently associated with soft tissue damage, especially
      when repeated reduction attempts are made. The magnitude of local and systemic
      inflammatory responses caused by prolonged and repeated reduction maneuvers has
      not been fully established. We devised an operative technique utilizing a robotic
      reduction device for use in a rat. A femoral fracture was simulated by means of
      an osteotomy. The robot enabled reproduction of both manual and guided precision
      reductions, performed in a single path movement. An external fixator was designed
      specifically to manipulate the rat femur and also for fixation of the osteotomy
      region. First, reduction accuracy was assessed in eight femurs, then the quality
      of fixator placement and reduction accuracy was analyzed in 22 femurs. In the
      first case, 100% of the femurs were accurately reduced. In the second case, 91%
      had successful stable fixation and an accurate reduction was achieved in 86% of
      the specimens. We demonstrated the feasibility of a model of robot-assisted
      fracture reduction that could be used to analyze the effects of reduction on the
      surrounding soft tissue via biochemical and histopathological means. A future
      aspect will be to evaluate whether the robot confers an advantage in fracture
      reduction versus the conventional technique, which would have significant
      implications for the use of robotic devices in orthopaedic surgery.

PMID- 18634015
TI  - Hypoxia upregulates the expression of angiopoietin-like-4 in human articular
      chondrocytes: role of angiopoietin-like-4 in the expression of matrix
      metalloproteinases and cartilage degradation.
AB  - The objective of this article was to investigate the role and expression of a
      novel adipocytokine, angiopoietin-like-4 (ANGPTL4), in arthropathy. Human
      chondrocytes were obtained from articular cartilage of patients with rheumatoid
      arthritis (RA) and osteoarthritis (OA), who underwent total knee or hip
      arthroplasty. Isolated chondrocytes were cultured under hypoxic (95% N(2), 5%
      CO(2)) or normoxic conditions. The effects of hypoxia on ANGPTL4 expression were
      determined by real-time reverse transcription polymerase chain reaction and
      Western blot analysis. We examined the role of ANGPTL4 using small interference
      RNA or by stimulating chondrocytes with recombinant ANGPTL4 protein. ANGPTL4
      expression in the articular cartilage specimens was examined by
      immunohistochemistry. Hypoxia induced a significant increase in ANGPTL4
      production (p < 0.05). Incubation of chondrocytes in vitro with recombinant
      ANGPTL4 enhanced the expression of matrix metalloproteinase (MMP)-1 and MMP-3.
      Downregulation of ANGPTL4 mRNA expression by siRNA diminished the expression of
      MMP-1, but not that of MMP-3, suggesting that each proteinase has a distinct
      response to ANGPTL4. Although the in vitro responses of chondrocytes to hypoxia
      were similar between RA and OA samples, the in vivo expression of ANGPTL4 had
      unique disease-specific patterns, suggesting differences in oxygen tension in
      vivo. Human chondrocytes expressed ANGPTL4 and the expression was enhanced by
      hypoxia. ANGPTL4 might modulate cartilage metabolism by regulating MMPs.

PMID- 18634016
TI  - Effect of cell-based VEGF gene therapy on healing of a segmental bone defect.
AB  - Fracture healing requires coordinated coupling between osteogenesis and
      angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role.
      We hypothesized that targeted over-expression of angiogenic and osteogenic
      factors within the fracture would promote bone healing by inducing development of
      new blood vessels and stimulating/affecting proliferation, survival, and activity
      of skeletal cells. Using a cell-based method of gene transfer, without viral
      vector, 5.0 x 10(6) fibroblasts transfected with VEGF were delivered to a 10-mm
      bone defect in rabbit tibiae (Group 1) (n = 9); control groups were treated with
      fibroblasts (Group 2) (n = 7), or saline (Group 3) (n = 7) only. After 12 weeks,
      eight tibial fractures healed in Group 1, compared to four each in Groups 2 and
      3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3,
      the defects were fibrous and sparsely ossified. Group 1 had more positively
      stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging
      of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT
      bone structural parameters showed significant differences between VEGF treatment
      and control groups (p < 0.05). These results indicate that the cell-based VEGF
      gene therapy has significant angiogenic and osteogenic effects to enhance healing
      of a segmental defect in the long bone of rabbits.

PMID- 18634017
TI  - Erythropoietin improves functional and histological recovery of traumatized
      skeletal muscle tissue.
AB  - Apart from its hematopoietic effect, erythropoietin (EPO) is known as pleiotropic
      cytokine with anti-inflammatory and anti-apoptotic properties. Here, we evaluated
      for the first time the EPO-dependent regeneration capacity in an in vivo rat
      model of skeletal muscle trauma. A myoblast cell line was used to study the
      effect of EPO on serum deprivation-induced cell apoptosis in vitro. A crush
      injury was performed to the left soleus muscle in 80 rats treated with either EPO
      or saline. Muscle recovery was assessed by analysis of contraction capacities.
      Intravital microscopy, BrdU/laminin double immunohistochemistry and cleaved
      caspase-3 immunohistochemistry of muscle tissue on days 1, 7, 14, and 42
      posttrauma served for assessment of local microcirculation, tissue integrity, and
      cell proliferation. Serum deprivation-induced myoblast apoptosis of 23.9 +/- 1.5%
      was reduced by EPO to 17.2 +/- 0.8%. Contraction force analysis in the EPO
      treated animals revealed significantly improved muscle strength with 10-20%
      higher values of twitch and tetanic forces over the 42-day observation period.
      EPO-treated muscle tissue displayed improved functional capillary density as well
      as reduced leukocytic response and consecutively macromolecular leakage over day
      14. Concomitantly, muscle histology showed significantly increased numbers of
      BrdU-positive satellite cells and interstitial cells as well as slightly lower
      counts of cleaved caspase-3-positive interstitial cells. EPO results in faster
      and better regeneration of skeletal muscle tissue after severe trauma and goes
      along with improved microcirculation. Thus, EPO, a compound established as
      clinically safe, may represent a promising therapeutic option to optimize the
      posttraumatic course of muscle tissue healing.

PMID- 18634018
TI  - Protective effects of preconditioned local somatothermal stimulation on
      neuromuscular plasticity against ischemia--reperfusion injury in rats.
AB  - The aim of this study was to investigate whether preconditioned local
      somatotheral stimulation (LSTS) protects the muscle and nerve against ischemia
      reperfusion (I/R) injuries. Male rats were randomly assigned to normal,
      preconditioned LSTS only, and I/R-injured groups with or without LSTS
      preconditioning. I/R injuries of the lower limb were induced by rubber band
      wrapping, followed by measurements of gait function and nerve conduction, muscle
      pathology, serum enzymatic activity, and the expression of heat-shock protein 70
      (HSP-70) in the gastrocnemius muscles. No significant change of neuromuscular
      function was found between LSTS (-) and LSTS (+) groups on the first day after
      I/R injury. In contrast, gait stride length, compound motor action potential, and
      serum creatine phosphokinase MM isoenzyme were significantly improved on the
      eighth day after one or two doses of preconditioned LSTS and subsequent I/R
      injury. Western blot analysis disclosed no significant change of HSP-70
      expression in the muscle of I/R injured limbs between LSTS (-) and LSTS (+)
      groups. We conclude that preconditioned LSTS is a safe modality that improves the
      neuromuscular plasticity against I/R injured limbs, which provides a new strategy
      for I/R injury in clinical applications, such as intraoperative use of
      tourniquets.

PMID- 18634019
TI  - NG2 expression predicts the metastasis formation in soft-tissue sarcoma patients.
AB  - Enhanced expression levels of NG2 proteoglycan in presurgical original lesions of
      soft-tissue sarcoma (STS) patients defines with 55% probability the immediate
      (i.e., within 12 months postsurgery) risk in these individuals to develop
      postsurgical secondary lesions, independently of any other clinical trait. It,
      therefore, provides a molecular factor that alone prospects a particularly
      unfavorable clinical outcome in such patients. Evaluation of the timing of
      metastasis formation in patients with high and low levels of NG2 in their
      primitive lesions further stratified the patients in subsets with diverse lag
      phases in the occurrence of metastatic disease. In our cohort of high-grade STS
      cases, transcription of NG2 also showed a 81-fold amplification in metastatic
      lesions, when compared to primitive ones, and this gene overexpression was
      accompanied by an abundant but nonuniform in situ expression of its product. In a
      similar manner as seen in primitive lesions, patients with higher levels of
      metastatic NG2 encountered a significantly more dismal clinical course.
      Multivariate analysis asserted that in these individuals upregulation of NG2
      represented an absolute independent prognostic parameter. Therefore, minimally
      invasive assessment of the transcription levels of the NG2 gene represents a
      parameter capable of predicting the arising of metastatic disease within a
      definite postsurgery time interval, and affords in adjunct in the definition of
      life expectance in STS patients.

PMID- 18634020
TI  - Gender-dependent association of the GNAS1 T393C polymorphism with early aseptic
      loosening after total hip arthroplasty.
AB  - The G-protein Galphas is involved in the physiology and pathophysiology of bone.
      Especially, Galphas is a key regulator of interleukin-6, which is a potent
      promoter of aseptic loosening. We hypothesized that the common single nucleotide
      polymorphism GNAS1 T393C could also affect time to aseptic loosening. Caucasian
      patients were genotyped for the GNAS1 T393C polymorphism. Time and median time to
      aseptic loosening were analyzed for dependency on GNAS1 genotypes. Time and
      median time were not significantly associated with genotypes. Additional analysis
      corrected for gender revealed, that the TT genotype was associated with
      significantly longer time (p = 0.048) as well as median time (p = 0.022) to
      aseptic loosening in female patients. In contrast to the findings in females,
      male TT genotype carriers had significantly shorter time (p = 0.018) and median
      time (p = 0.023) to aseptic loosening. Compared with TT genotype carriers
      heterozygous patients had a 6.25-fold lower risk with a hazard ratio of 0.160 (p
      = 0.016) and male patients carrying the CC genotype had an 11-fold lower risk
      with a hazard ratio of 0.088 (p = 0.006) in multivariate analysis. The present
      study suggests a significant gender-dependent role of the T393C polymorphism in
      aseptic loosening. The apparently contradictory results in women and men and the
      finding that the GNAS1 T393C genotype is an independent factor for time to
      aseptic loosening in male patients assigned this polymorphism as an interesting
      target for further investigations in bone diseases.

PMID- 18634021
TI  - The accessory olfactory bulb in the adult rat: a cytological study of its cell
      types, neuropil, neuronal modules, and interactions with the main olfactory
      system.
AB  - The accessory olfactory bulb (AOB) in the adult rat is organized into external
      (ECL) and internal (ICL) cellular layers separated by the lateral olfactory tract
      (LOT). The most superficial layer, or vomeronasal nerve layer, is composed of two
      fiber contingents that distribute in rostral and caudal halves. The second layer,
      or glomerular layer, is also divided by a conspicuous invagination of the
      neuropil of the ECL at the junction of the rostral and caudal halves. The ECL
      contains eight cell types distributed in three areas: a subglomerular area
      containing juxtaglomerular and superficial short-axon neurons, an intermediate
      area harboring large principal cells (LPC), or mitral and tufted cells, and a
      deep area containing dwarf, external granule, polygonal, and round projecting
      cells. The ICL contains two neuron types: internal granule (IGC) and main
      accessory cells (MACs). The dendrites and axons of LPCs in the two AOB halves are
      organized symmetrically with respect to an anatomical plane called linea alba.
      The LPC axon collaterals may recruit adjacent intrinsic, possibly gamma
      aminobutyric acid (GABA)-ergic, neurons that, in turn, interact with the
      dendrites of the adjacent LPCs. These modules may underlie the process of
      decoding pheromonal clues. The most rostral ICL contains another neuron group
      termed interstitial neurons of the bulbi (INBs) that includes both intrinsic and
      projecting neurons. MACs and INBs share inputs from fiber efferents arising in
      the main olfactory bulb (MOB) and AOB and send axons to IGCs. Because IGCs are a
      well-known source of modulatory inputs to LPCs, both MACs and INBs represent a
      site of convergence of the MOB with the AOB.

PMID- 18634023
TI  - Can conformational changes be responsible for solvent and excipient effects on
      the catalytic behavior of subtilisin Carlsberg in organic solvents?
AB  - We developed an FTIR (Fourier transform infrared) methodology for quantitatively
      assessing the secondary structure of proteins suspended in nonaqueous media. This
      methodology was used to measure the percentages of alpha-helices and beta-sheets
      of subtilisin Carlsberg, prepared under different conditions, placed in various
      organic solvents. The title question was addressed with respect to some instances
      of markedly influencing the subtilisin activity in organic solvents reported in
      the literature. It is concluded that the mechanism of subtilisin activation by
      KCl and N-Ac-L-Phe-NH(2) present in the aqueous solution of the enzyme prior to
      lyophilization may be due to their preservation of the secondary structure,
      otherwise altered by the dehydration. Likewise, subtilisin inactivation in the
      protein-dissolving solvent DMSO (dimethyl sulfoxide) is likely caused by enzyme
      denaturation (the loss of both alpha-helices and beta-sheets). On the other hand,
      some other ligands, as well as protein nondissolving organic solvents, while
      greatly affecting the subtilisin activity, have little effect on its secondary
      structure, thus ruling out the causal relationship between the two. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 53: 351-362, 1997.

PMID- 18634022
TI  - Functional and computational assessment of missense variants in the ataxia
      telangiectasia mutated (ATM) gene: mutations with increased cancer risk.
AB  - The functional consequences of missense variants are often difficult to predict.
      This becomes especially relevant when DNA sequence changes are used to determine
      a diagnosis or prognosis. To analyze the consequences of 12 missense variants in
      patients with mild forms of ataxia-telangiectasia (A-T), we employed site
      directed mutagenesis of ataxia-telangiectasia mutated (ATM) cDNA followed by
      stable transfections into a single A-T cell line to isolate the effects of each
      allele on the cellular phenotype. After induction of the transfected cells with
      CdCl2, we monitored for successful ATM transcription and subsequently assessed:
      1) intracellular ATM protein levels; 2) ionizing radiation (IR)-induced ATM
      kinase activity; and 3) cellular radiosensitivity. We then calculated SIFT and
      PolyPhen scores for the missense changes. Nine variants produced little or no
      correction of the A-T cellular phenotype and were interpreted to be ATM
      mutations; SIFT/PolyPhen scores supported this. Three variants corrected the
      cellular phenotype, suggesting that they represented benign variants or
      polymorphisms. SIFT and PolyPhen scores supported the functional analyses for one
      of these variants (c.1709T>C); the other two were predicted to be "not tolerated"
      (c.6188G>A and c.6325T>G) and were classified as "operationally neutral."
      Genotype/phenotype relationships were compared: three deleterious missense
      variants were associated with an increased risk of cancer (c.6679C>T, c.7271T>G,
      and c.8494C>T). In situ mutagenesis represents an effective experimental approach
      for distinguishing deleterious missense mutations from benign or operationally
      neutral missense variants.

PMID- 18634024
TI  - Substrate utilization and mass transfer in an autotrophic biofilm system:
      Experimental results and numerical simulation.
AB  - An autotrophic biofilm has been investigated for over 10 months in a biofilm tube
      reactor. The objective of this investigation was the verification and improvement
      of a biofilm model. The use of a Clark-type oxygen microelectrode in situ allowed
      the determination of the substrate flux in the biofilm. Also, the population
      dynamics of the autotrophic bacteria could be evaluated by varying the substrate
      conditions. Simulation of the experimental results showed that the liquid phase
      of the biofilm decreased with biofilm depth. This could be described by a
      logistic function. The density of the inert volume fraction was found to be
      higher than that of the viable bacteria. This was verified in a nonsubstrate
      phase of 5 weeks. Growth and decay of the autotrophic bacteria could be described
      by the growth, endogenous respiration, and death processes. Mass transfer
      coefficients at the bulk/biofilm interface were evaluated. They were found to be
      one order of magnitude higher than those known from hydrodynamics in tubes
      without a biofilm. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 363
      371, 1997.

PMID- 18634025
TI  - Real-time monitoring and control of glucose and lactate concentrations in a
      mammalian cell perfusion reactor.
AB  - On-line monitoring and control of cell culture fermentation is important for
      optimal and consistent production of biologicals. In this work, glucose and
      lactate concentrations are monitored on-line using a commercially available
      analyzer (Model 2700, Yellow Springs Instruments, Yellow Springs, OH) during
      batch and perfusion hybridoma cell fermentation. Cell free samples from the
      reactor are obtained using a 0.45 mum hollow fiber filtering system placed in a
      circulation loop. The samples were analyzed at specified times and the data are
      collected on a computer. A process control strategy was developed to control the
      concentrations of glucose and lactate in a perfusion reactor where the feed rate
      is adjusted to maintain their concentrations at desired set points. Hybridoma
      cells (A10G10) were cultivated in a high density perfusion culture where cell
      density increased from 2 to 14 million cells/mL. During this period the control
      algorithm successfully adjusted the perfusion rate while maintaining constant
      glucose and lactate concentrations. Glucose consumption and lactate accumulation
      rates as well as net lactate yield on glucose were monitored continuously during
      perfusion culture. These metabolic rates were observed to be independent of cell
      concentration and were used for the estimation of viable cell density in the
      reactor. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 372-378, 1997.

PMID- 18634026
TI  - Improvement in recombinant protein production in ppGpp-deficient Escherichia
      coli.
AB  - Maintaining a metabolically productive state for recombinant Escherichia coli
      remains a central problem for a wide variety of growth-dependent biosynthesis.
      This problem becomes particularly acute under conditions of minimal cell growth
      such as fed-batch fermentations. In this, we investigated the possibility of
      manipulating the protein synthesis machinery of E. coli whereby synthesis of
      foreign proteins might be decoupled from cell growth. In particular, the effects
      of eliminating intracellular ppGpp on the synthesis of foreign proteins were
      studied in both batch and fed-batch operations. A significant increase in CAT
      production was observed from the ppGpp-deficient strain during both exponential
      and fed-batch phases. The increase in CAT production during exponential growth
      was accompanied by a simultaneous increase in CAT mRNA levels. Interestingly, CAT
      production was increased five-fold, while the level of CAT-specific mRNA
      increased only three-fold. Thus, eliminating intracellular ppGpp appears to have
      increase the production of recombinant protein by increasing not only the pool
      sizes of CAT mRNA but also possible alternations in the post-transcriptional
      processes. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 379-386, 1997.

PMID- 18634027
TI  - Peptide condensation activity of a neutral protease from Vibrio sp. T1800
      (Vimelysin).
AB  - Condensation of Cbz-Asp and PheOMe catalyzed by a neutral protease from Vibrio
      sp. T1800 (Vimelysin: VLN) was studied. VLN showed a relatively higher catalytic
      activity of condensation and an apparently larger yield after 3 h or 24 h, in
      comparison with thermolysin (TLN), especially at lower pH and temperatures.VLN
      showed higher solvent-tolerance than TLN. TLhe apparent highest yield (25%) was
      obtained in 30% DMSO by using VLN; under similar conditions, TLN gave only about
      a half of this value. The rate of the condensation reaction per mole of enzyme
      (v/[E](o)) in DMSO 50% at 37 degrees C and pH 6.5 was 0.16 s(-1) for VLN and
      0.047 s(-1) for TLN. In 30% ethanol VLN showed more than three-fold peptide yield
      than TLN after 5 h reaction. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng
      53: 387-390, 1997.

PMID- 18634028
TI  - Enzymatic assay of cholesterol by reaction rate measurements.
AB  - A dynamic method for free and total cholesterol assay based on the oxidation of
      cholesterol by cholesterol oxidase, and conversion of cholesteryl oleate to
      cholesterol by cholesterol esterase is discussed in this article. The reaction
      conditions for total cholesterol assay were a temperature of 310 K and pH of 7.4.
      For conversion of cholesteryl oleate to cholesterol, the samples were incubated
      with 0.6 unit/mL of cholesterol esterase and 0.02 g/mL of taurocholate. The
      determination of initial reaction rates in the oxidation of free cholesterol,
      which is directly related to the cholesterol concentration, was found to be
      rapid, reliable, and inexpensive. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 53: 391-396, 1997.

PMID- 18634029
TI  - Control of heterotrophic layer formation on nitrifying biofilms in a biofilm
      airlift suspension reactor.
AB  - A Biofilm Airlift Suspension (BAS) reactor was operated with nitrifying biofilm
      growth and heterotrophic suspended growth, simultaneously converting ammonium and
      acetate. Growth of heterotrophs in suspension decreases the diffusion limitation
      for the nitrifiers, and enlarges the nitrifying capacity of a biofilm reactor.
      Neither nitrifiers nor heterotrophs suffer from additional oxygen diffusion
      limitation when the heterotrophs grow in suspension. Control of the location of
      heterotrophic growth, either in suspension or in biofilms over the nitrifying
      biofilms, was possible by manipulation of the hydraulic retention time. A time
      delay for formation and disappearance of the heterotrophic biofilms of 10 to 15
      days was observed. Surprisingly, it was found that in the presence of the
      heterotrophic layers the maximum specific activity on ammonia of the nitrifying
      biofilms increased. The reason for the increase in activity is unknown. The
      effect of heterotrophic biofilm formation on oxygen diffusion limitation for the
      nitrifiers is discussed. Some phenomena compensating the increased mass transfer
      resistance due to the growth of a heterotrophic layer are also presented. (c)
      1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 397-405, 1997.

PMID- 18634030
TI  - Bioaffinity separation of trypsin using trypsin inhibitor immobilized in reverse
      micelles composed of a nonionic surfactant.
AB  - Trypsin inhibitor was converted to hydrophobic states by covalently combining
      cholesteryl groups using an acylation reaction, and was immobilized in reverse
      micelles composed of a nonionic surfactant. Using this reverse micellar phase
      containing trypsin inhibitor as an affinity ligand, trypsin was selectively
      separated with high recoveries from a mixture of several kinds of contaminating
      proteins by forward and backward extraction. No loss of activity of the recovered
      trypsin was observed through these operations. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 53: 406-408, 1997.

PMID- 18634031
TI  - Acetylation of pea isolate in a torus microreactor.
AB  - Acetylation, which acts on the amino groups of proteins, allows to increase the
      solubility and the emulsifying properties of pea isolate. Acetylation by acetic
      anhydride was carried out in a torus microreactor in semibatch and continuous
      conditions. The mixing characteristics, obtained by a residence time distribution
      (RTD) method, are the same in batch and continuous processes. The maximum
      acetylation degree reached by the torus reactor is higher than with the stirred
      reactor. Torus reactors are more efficient than stirred ones as shown by a
      conversion efficiency, defined by the quantity of modified lysine groups by
      consumed acetic anhydride. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53:
      409-414, 1997.

PMID- 18634032
TI  - Cell-substratum adhesion strength as a determinant of hepatocyte aggregate
      morphology.
AB  - Cultured hepatocytes typically form multicellular aggregates which are either
      monolayered or spheroidal in morphology. We propose that the aggregate morphology
      resulting from a particular cell-substratum interaction has a biophysical basis:
      when cell contractile forces are greater than cell-substratum adhesion forces,
      spheroidal aggregates form; when cell contractile forces are weaker than cell
      substratum adhesion forces, cells remain essentially spread and form monolayered
      aggregates. We tested this hypothesis by systematically varying the morphology of
      hepatocellular aggregates formed on substrata coated with a series of different
      concentrations of Matrigel, and correlating aggregate morphology with the cell
      substratum adhesion strength measured in a shear flow detachment assay. Aggregate
      morphology was binary-spheroidal aggregates formed at low Matrigel concentrations
      and monolayered aggregates formed at high Matrigel concentrations. Cell
      substratum adhesion strength was similarly binary, with low adhesion strengths
      correlated with spheroidal aggregates and high adhesion strengths correlated with
      formation of monolayered aggregates. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 53: 415-426, 1997.

PMID- 18634033
TI  - A new approach to continuous counter-current protein chromatography: Direct
      purification of malate dehydrogenase from a Saccharomyces cerevisiae homogenate
      as a model system.
AB  - A novel technique for protein chromatography has been developed, which can be
      used to extract proteins from particulate-containing solutions (such as
      fermentation broths or preparations of disrupted cells) on a continuous basis,
      and delivers clarified streams of purified product. Adsorbents deployed in this
      type of contactor are based on PVA-coated perfluorocarbons derivitized with
      affinity ligands such as triazine dyes. In this article, we describe the
      application of this equipment for the continuous purification of malate
      dehydrogenase from an unclarified homogenate of Saccharomyces cerevisiae, using a
      Procion Red HE-7B-derivitized adsorbent. Although operating conditions were not
      optimized to produce a product of maximized purification factor, concentration,
      and yield, we have shown that MDH can be purified continuously in 78% yield at a
      rate of 70 U/min, with a purification factor of approximately 10. This
      corresponds to specific productivity of approximately 0.35 U/min per milliliter
      of settled adsorbent, a higher specific productivity than was feasible with the
      same adsorbent using expanded bed adsorption (EBA). (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 53: 427-441, 1997.

PMID- 18634034
TI  - Common genetic variants in pre-microRNAs were associated with increased risk of
      breast cancer in Chinese women.
AB  - Small, noncoding RNA molecules, called microRNAs (miRNAs), are thought to
      function as either tumor suppressors or oncogenes. Common single-nucleotide
      polymorphisms (SNPs) in miRNAs may change their property through altering miRNA
      expression and/or maturation, and thus they may have an effect on thousands of
      target mRNAs, resulting in diverse functional consequences. However, it remains
      largely unknown whether miRNA SNPs may alter cancer susceptibility. We evaluated
      the associations of selected four SNPs (rs2910164, rs2292832, rs11614913, and
      rs3746444) in pre-miRNAs (hsa-mir-146a, hsa-mir-149, hsa-mir-196a2, and hsa-mir
      499) with breast cancer risk in a case-control study of 1,009 breast cancer cases
      and 1,093 cancer-free controls in a population of Chinese women and we found that
      hsa-mir-196a2 rs11614913:T>C and hsa-mir-499 rs3746444:A>G variant genotypes were
      associated with significantly increased risks of breast cancer (odds ratio [OR],
      1.23; 95% confidence interval [CI], 1.02-1.48 for rs11614913:T>C; and OR, 1.25;
      95% CI, 1.02-1.51 for rs3746444:A>G in a dominant genetic model) in a dose-effect
      manner (P for trend was 0.010 and 0.037, respectively). These findings suggest,
      for the first time, that common SNPs in miRNAs may contribute to breast cancer
      susceptibility. Further functional characterization of miRNA SNPs and their
      influences on target mRNAs may provide underlying mechanisms for the observed
      associations and disease etiology.

PMID- 18634035
TI  - Matrix metalloproteinases and their tissue inhibitors as prognostic indicators
      for diagnostic and surgical recurrence in Crohn's disease.
AB  - BACKGROUND: Recurrence of disease after surgically induced remission constitutes
      a major and largely unpredictable problem in Crohn's disease (CD). Matrix
      metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMP)
      are involved in the (etio)pathogenesis of CD and may thereby also affect
      postsurgical outcome. We studied the predictive value of 1) allelic composition
      at MMP, TIMP, and TNF-alpha single nucleotide polymorphism loci, and 2) MMP and
      TIMP intestinal protein levels relative to important clinical variables for
      recurrence of CD after resection of diseased bowel. METHODS: From 87 CD patients
      with a full medical record, surgically resected tissue was homogenized and
      analyzed for single nucleotide polymorphism (SNP) genotype and MMP-TIMP protein
      levels. The prognostic value of these parameters was determined using the uni-
      and multivariate Cox proportional hazards analyses. RESULTS: The T allele at TIMP
      1 SNP +372 T/C was found to be associated with an increased risk for surgical
      recurrence. Higher levels of TIMP-1, TIMP-2, and MMP-9 in noninflamed CD tissue,
      but not in inflamed tissue, and negative smoking status independently protected
      against diagnostic and/or surgical recurrence. CONCLUSIONS: The TIMP-1 SNP +372 T
      allele with an increased risk of recurrence is in line with our previous results
      demonstrating increased CD susceptibility and low TIMP-1 protein expression
      associated with this allele. High TIMP and MMP-9 levels in noninflamed tissue are
      predictive of a favorable disease recurrence in CD. The contribution of MMP-9 and
      TIMPs to disease recurrence appears not to be mediated by smoking status, since
      no correlation with this parameter could be demonstrated.

PMID- 18634036
TI  - The epidermal growth factor receptor ligand amphiregulin participates in the
      development of mouse liver fibrosis.
AB  - The hepatic wound-healing response to chronic noxious stimuli may lead to liver
      fibrosis, a condition characterized by excessive deposition of extracellular
      matrix. Fibrogenic cells, including hepatic stellate cells and myofibroblasts,
      are activated in response to a variety of cytokines, growth factors, and
      inflammatory mediators. The involvement of members of the epidermal growth factor
      family in this process has been suggested. Amphiregulin (AR) is an epidermal
      growth factor receptor (EGFR) ligand specifically induced upon liver injury.
      Here, we have addressed the in vivo role of AR in experimental liver fibrosis. To
      this end, liver fibrosis was induced in AR+/+ and AR-/- mice by chronic CCl(4)
      administration. Histological and molecular markers of hepatic fibrogenesis were
      measured. Additionally, the response of cultured human and mouse liver fibrogenic
      cells to AR was evaluated. We observed that AR was expressed in isolated Kupffer
      cells and liver fibrogenic cells in response to inflamatory stimuli and platelet
      derived growth factor, respectively. We demonstrate that the expression of alpha
      smooth muscle actin and collagen deposition were markedly reduced in AR-/- mice
      compared to AR+/+ animals. AR-/- mice also showed reduced expression of tissue
      inhibitor of metalloproteinases-1 and connective tissue growth factor, two genes
      that responded to AR treatment in cultured fibrogenic cells. AR also stimulated
      cell proliferation and exerted a potent antiapoptotic effect on isolated
      fibrogenic cells. CONCLUSION: These results indicate that among the different
      EGFR ligands, AR plays a specific role in liver fibrosis. AR may contribute to
      the expression of fibrogenic mediators, as well as to the growth and survival of
      fibrogenic cells. Additionally, our data lend further support to the role of the
      EGFR system in hepatic fibrogenesis.

PMID- 18634037
TI  - Plantar pressure distribution in older people with osteoarthritis of the first
      metatarsophalangeal joint (hallux limitus/rigidus).
AB  - The purpose of this study was to evaluate differences in dynamic plantar pressure
      distribution between older people with and without radiographically confirmed
      osteoarthritis (OA) of the first metatarsophalangeal joint (first MPJ) of the
      foot. Dynamic plantar pressure recordings using the TekScan MatScan system were
      obtained during barefoot level walking in 40 older participants; 20 with
      radiographically confirmed OA of the first MPJ displaying less than 55 degrees of
      passive dorsiflexion, and 20 with no evidence of OA in the first MPJ displaying
      greater than 55 degrees of passive dorsiflexion. Group comparisons between the
      variables maximum force and peak pressure were made for seven different regions
      underneath the right foot (heel, midfoot, first MPJ, second MPJ, third to fifth
      MPJs, hallux, and lesser toes). Compared to the control group, participants with
      OA of the first MPJ exhibited 34% greater maximum force (7.9 +/- 2.5 vs. 5.9 +/-
      1.7 kg, p = 0.005) and 23% higher peak pressure (1.6 +/- 0.3 vs. 1.3 +/- 0.3
      kg/cm(2), p = 0.001) under the hallux. Similar results were also found under the
      lesser toes with 43% greater maximum force (5.0 +/- 1.9 vs. 3.5 +/- 1.4 kg; p =
      0.006) and 29% higher peak pressure (0.9 +/- 0.2 vs. 0.7 +/- 0.2 kg/cm(2), p =
      0.018). No significant differences were found to exist between groups for any
      other plantar region. These findings indicate that OA of the first MPJ is
      associated with significant changes in load-bearing function of the foot, which
      may contribute to the development of secondary pathological changes associated
      with the condition, such as plantar callus formation and hyperextension of the
      hallux interphalangeal joint.

PMID- 18634038
TI  - Serum ion levels after ceramic-on-ceramic and metal-on-metal total hip
      arthroplasty: 8-year minimum follow-up.
AB  - Alternative bearing surfaces for total hip arthroplasty, such as metal-on-metal
      and ceramic-on-ceramic, offer the potential to reduce mechanical wear and
      osteolysis. In the short and medium term, the second generation of metal-on-metal
      bearings demonstrated high systemic metal ion levels, whereas ceramic-on-ceramic
      bearings showed the lowest ones. We aimed to verify whether the long-term ion
      release in metal-on-metal subjects was still relevant at a median 10-year follow
      up, and whether a fretting process at the modular junctions occurred in ceramic
      on-ceramic patients and induced an ion dissemination. Serum levels were measured
      in 32 patients with alumina-on-alumina implants (group A), in 16 subjects with
      metal-on-metal implants (group B), and in 47 healthy subjects (group C). Group B
      results were compared with medium-term findings. Cobalt and chromium levels were
      significantly higher in metal-on-metal implants than in ceramic-on-ceramic ones
      and controls. Nevertheless, ion levels showed a tendency to decrease in
      comparison with medium-term content. In ceramic-on-ceramic implants, ion values
      were not significantly different from controls. Both in groups A and B, aluminum
      and titanium release were not significantly different from controls. In
      conclusion, negligible serum metal ion content was revealed in ceramic-on-ceramic
      patients. On the contrary, due to the higher ion release, metal-on-metal coupling
      must be prudently considered, especially in young patients, in order to obtain
      definitive conclusions.

PMID- 18634039
TI  - Fermentation database mining by pattern recognition.
AB  - A large volume of data is routinely collected during the course of typical
      fermentation and other processes. Such data provide the required basis for
      process documentation and occasionally are also used for process analysis and
      improvement. The information density of these data is often low, and automatic
      condensing, analysis, and interpretation ("database mining") are highly
      desirable. In this article we present a methodology whereby process variables are
      processed to create a database of derivative process quantities representative of
      the global patterns, intermediate trends, and local characteristics of the
      process. A powerful search algorithm subsequently attempts to extract the
      specific process variables and their particular attributes that uniquely
      characterize a class of process outcomes such as high- or low-yield
      fermentations.The basic components of our pattern recognition methodology are
      described along with applications to the analysis of two sets of data from
      industrial fermentations. Results indicate that truly discriminating variables do
      exist in typical fermentation data and they can be useful in identifying the
      causes or symptoms of different process outcomes. The methodology has been
      implemented in a user-friendly software, named db-miner, which facilitates the
      application of the methodology for efficient and speedy analysis of fermentation
      process data. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 443-452,
      1997.

PMID- 18634040
TI  - Chemical treatment of Escherichia coli: 1. Extraction of intracellular protein
      from uninduced cells.
AB  - Extraction of intracellular protein from Escherichia coli is traditionally
      achieved by mechanical disruption. A chemical treatment that destroys the
      integrity of the bacterial cell wall and could provide an alternative technique
      is examined in this study. Treatment with a combination of the chelating agent
      ethylenediaminetet-raacetate (EDTA) (greater than 0.3 mM) and the chaotropic
      agent urea (6 M) is highly effective at releasing protein from uninduced E. coli.
      The 6 M urea in the presence of 3 mM EDTA can release cytoplasmic protein from
      both logarithmic-phase and stationary-phase E. coli cells at levels equivalent to
      mechanical disruption. The concentrations of the two chemical agents were the
      major variables affecting the maximum levels of protein release. Several minor
      variables and interactions were also identified. The kinetics of protein release
      is first order. For 2, 4, and 6 M urea with 3 mM EDTA, the time constant is
      approximately 2.5 min independent of urea concentration. Kinetics for 3 mM EDTA
      without urea is considerably slower, with a time constant of 12.3 min. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 53: 453-458, 1997.

PMID- 18634041
TI  - Uptake and release of inert fluorescence particles by mixed population biofilms.
AB  - Inert fluorescent microparticles were used as tracers to investigate the dynamics
      of spatial distribution of particulate components in mixed population biofilms.
      The tracer bead spatial distributions in the biofilm were experimentally measured
      by sectioning the biofilms with a microslicer. The experimental results were
      compared with model simulations using the biofilm model (BIOSIM) to evaluate the
      assumption that advective transport (displacement) of particulates balances with
      cell growth in the model. The tracer beads could traverse throughout a biofilm
      360 microm thick within less than 23 minutes, which cannot be explained solely by
      their attachment to the surface followed by molecular diffusion. Advective
      transport of the tracer beads via "voids and pores" could be responsible for such
      rapid bead penetration. Observation by confocal scanning laser microscopy (CSLM)
      clearly showed that the biofilm consisted of a thick loose surface layer, varying
      in thickness, and a semicontiguous base layer separated by water channels. About
      80% of attached tracer beads remained in the biofilm for over 20 days. The
      trapped tracer beads were gradually transferred from the depth of the biofilm to
      the surface. The observed bead release rate was much slower than the model
      predictions. This is probably because the cell density increased predominantly
      near the substratum, resulting in an unbalance of advective transport of the
      tracer beads and cell growth. The pores, voids, and cell-free spaces in the
      biofilm were first filled with growing biomass, thereafter, displacement of the
      beads took place once the cell density reached certain levels. The model
      assumptions of the temporal and spatial constant cell density and the continuum
      concept (flat biomass) are clearly oversimplified and should be revised. It was
      concluded that the dynamics of the inert microbeads in the biofilm was strongly
      influenced by not only microbial growth, but also by the biofilm structure and
      growth pattern. Therefore, one dimensional modeling is not adequate for the
      accurate description of the transport of particulates in a biofilm. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 53: 459-469, 1997.

PMID- 18634042
TI  - Kinetics and modeling of GM-CSF production by recombinant yeast in a three-phase
      fluidized bed bioreactor.
AB  - Continuous production of a recombinant murine granulocyte-macrophage colony
      stimulating factor (GM-CSF) by Saccharomyces cerevisiae strain XV2181 (a/a, Trp
      1) containing plasmid palphaADH2 and immobilized on porous glass beads in a
      fluidized bed bioreactor was studied. Kinetic models for plasmid stability, cell
      growth, and protein production in the three-phase fluidized bed bioreactor were
      developed and used to study the effects of solid loading or cell immobilization
      on plasmid stability and recombinant protein production. With increasing cell
      immobilization or solid loading in the bioreactor, plasmid stability and protein
      production improved significantly. The improvements could be attributed to the
      decreased theta value, which is the plasmid loss probability during cell division
      and is an indication of segregational instability of the recombinant cell, and
      the increased alpha value, which is the ratio of the specific growth rate of a
      plasmid-carrying cell to that of a plasmid-free cell and is indicative of
      competitive stability of the recombinant cell culture. theta decreased from 0.552
      to 0.042 and alpha increased from 0.351 to 0.991 when solid loading in the
      bioreactor was increased from 5% (v/v) to 33%. The model simulation also showed
      that the specific growth rate of cells in the bioreactor was lower at higher
      solid loading. This indicated that there was significant mass transfer
      limitation, particularly for oxygen transfer, when the total cell density in the
      bioreactor was high at high solid loading. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 53: 470-477, 1997.

PMID- 18634043
TI  - A kinetic model for biological oxidation of ferrous iron by Thiobacillus
      ferrooxidans.
AB  - The kinetics of bacterial oxidation of ferrous iron in the presence of
      Thiobacillus ferrooxidans cells were studied using an initial-rate method.
      Measurements of the redox potential of the solution during the oxidation of
      ferrous iron were used to assess the initial rate of the reaction. Effects on the
      rate of reaction were determined for ferrous iron concentration in the range 0.25
      to 30 kg m(-3), bacterial concentration in the range 3.25 x 10(7) to 4.47 x 10(8)
      cells mL(-1), and temperature in the range 20 to 35 degrees C. Using these
      experimental results and an approach based on Michaelis-Menten kinetics, a model
      for biological oxidation of ferrous iron was developed. The model, which
      incorporates terms for the effect of temperature and substrate and cell
      inhibition, was successfully used to simulate the full range of experimental data
      obtained. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 478-486, 1997.

PMID- 18634044
TI  - Mathematical model for characterization of bacterial migration through sand
      cores.
AB  - The migration of chemotactic bacteria in liquid media has previously been
      characterized in terms of two fundamental transport coefficients-the random
      motility coefficient and the chemotactic sensitivity coefficient. For modeling
      migration in porous media, we have shown that these coefficients which appear in
      macroscopic balance equations can be replaced by effective values that reflect
      the impact of the porous media on the swimming behavior of individual bacteria.
      Explicit relationships between values of the coefficients in porous and liquid
      media were derived. This type of quantitative analysis of bacterial migration is
      necessary for predicting bacterial population distributions in subsurface
      environments for applications such as in situ bioremediation in which bacteria
      respond chemotactically to the pollutants that they degrade.We analyzed bacterial
      penetration times through sand columns from two different experimental studies
      reported in the literature within the context of our mathematical model to
      evaluate the effective transport coefficients. Our results indicated that the
      presence of the porous medium reduced the random motility of the bacterial
      population by a factor comparable to the theoretical prediction. We were unable
      to determine the effect of the porous medium on the chemotactic sensitivity
      coefficient because no chemotactic response was observed in the experimental
      studies. However, the mathematical model was instrumental in developing a
      plausible explanation for why no chemotactic response was observed. The chemical
      gradients may have been too shallow over most of the sand core to elicit a
      measurable response. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 487
      496, 1997.

PMID- 18634045
TI  - Optimization by experimental design of polyacrylamide gel composition as support
      for enzyme immobilization by entrapment.
AB  - We have developed a methodology based on experimental design, to optimize a
      polyacrylamide gel as the support for enzyme immobilization, taking advantage of
      all the properties which this type of gel has. Monomer and crosslinking agent
      proportions are responsible for both the porous structure and pore size of the
      gel. A correct selection of those variables and suitable synthesis conditions
      leads to an increase in the activity retained by the gel. The path of steepest
      ascent method was used to obtain the relative maximum activity. The maximum
      retained activity was chosen with a central composite design in terms of the gel
      composition. The retained activity in the network, loss activity in the wash
      water, and loss activity due to steric impediment or blockage was modeled in
      terms of the variables responsible for the gel structure. (c) 1997 John Wiley &
      Sons, Inc. Biotechnol Bioeng 53: 497-506, 1997.

PMID- 18634046
TI  - Study of stability of recombinant plasmids during the continuous culture of
      Bacillus stearothermophilus NUB3621 in nonselective medium.
AB  - The optimal culture conditions for Bacillus stearothermophilus NUB3621 (BGSC 9A5)
      in chemostat were studied. The results obtained showed that the optimal culture
      conditions in terms of biomass concentration and maximum growth rate were 65
      degrees C, pH 6.8 to 7.2. Dissolved oxygen became growth limiting at pO(2) levels
      below 10%. Furthermore, this strain was transformed with three new hybrid vectors
      (pPAM2, pPCH2, or pPLY2) constructed by cloning in pRP9, a plasmid based on the
      thermophilic replicon, pBC1, and three heterologous genes: the alpha-amylase gene
      from Bacillus licheniformis, the cholesterol oxidase gene from Streptomyces sp.,
      and the lipase gene from Pseudomonas fluorescens. The influence of several
      fermentative conditions on segregational and structural stability of the
      recombinant B. stearothermophilus NUB3621 transformants was studied.The
      parameters of plasmid loss, that is, rate of plasmid loss (R) and specific growth
      rate difference (deltamu), were calculated. B. stearothermophilus NUB3621
      carrying pRP9 showed great segregational stability in all the assayed conditions,
      exceeding more than 300 generations without significant plasmid loss, whereas
      NUB3621 carrying pPAM2, pPCH2, or pPLY2 exhibited relatively low plasmid
      stability. The segregational instability of the recombinant constructs increased
      by increasing the fermentation temperature, decreased by increasing the dilution
      rate, and was not affected by the level of dissolved oxygen. On the other hand,
      plasmid maintenance decreased in minimal medium if compared with the results
      obtained in complex medium. Restriction analyses carried out on cultures of
      NUB3621 carrying pRP9, pPAM2, pPCH2, or pPLY2, grown for 200 generations on
      nonselective media, revealed that all the clones tested contained the parental
      plasmids. These results indicate that the heterologous inserts did not affect the
      structural stability of the recombinant plasmids. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 53: 507-514, 1997.

PMID- 18634047
TI  - Biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by a
      prospective consortium and its most effective isolate Serratia marcescens.
AB  - The biotransformation of hexahydro-1,3,5-trinitro-1,3,5 triazine (RDX) has been
      observed in liquid culture by a consortium of bacteria found in horse manure.
      Five types of bacteria were found to predominate in the consortium and were
      isolated. The most effective of these isolates at transforming RDX was Serratia
      marcescens. The biotransformation of RDX by all of these bacteria was found to
      occur only in the anoxic stationary phase. The process of bacterial growth and
      RDX biotransformation was quantified for the purpose of developing a predictive
      type model. Cell growth was assumed to follow Monod kinetics. All of the aerobic
      and anoxic growth parameters were determined: micro(max), K(s), and Y(x/s). RDX
      was found to competitively inhibit cell growth in both atmospheres. Degradation
      of RDX by Serratia marcescens was found to proceed through the stepwise reduction
      of the three nitro groups to nitroso groups. Each of these reductions was found
      to be first order in both component and cell concentrations. The degradation rate
      constant for the first step in this reduction process by the consortium was 0.022
      L/g cells . h compared to 0.033 L/g cells . h for the most efficient isolate. (c)
      1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 515-522, 1997.

PMID- 18634048
TI  - Capture of microbial cells on brush-type polymeric materials bearing different
      functional groups.
AB  - A brush-type microbial-cell-capturing polymeric material was prepared by
      radiation-induced grafting of an epoxy-group-containing monomer, glycidyl
      methacrylate (GMA), onto a polyethylene-based fiber. The epoxy ring (EO) of GMA
      was opened with different degrees of introduction of diethylamine (DEA). The
      residual epoxy group was hydrophilized by ethanolamine (EA). The prepared DEA
      membranes with coexisting EO or EA groups were tested for their ability to
      capture Staphylococcus aureus and Escherichia coli cells. The DEA membrane (2.7
      mol/kg of product of DEA group density) with coexisting EO groups (DEA-EO
      membrane) exhibited good S. aureus-cell-capturing ability with a capturing rate
      constant of 1.82 x 10(-6) m/s, whereas the DEA membrane with coexisting EA groups
      (DEA-EA membrane) retarded capturing abilities for both S. aureus and E. coli
      cells. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 523-528, 1997.

PMID- 18634049
TI  - Effects of rheological change by addition of carboxymethylcellulose in culture
      media of an air-lift fermentor on poly-D-3-hydroxybutyric acid productivity in
      autotrophic culture of hydrogen-oxidizing bacterium, Alcaligenes eutrophus.
AB  - The effects of rheological change by addition of sodium carboxymethylcellulose
      (CMC) to culture medium in an air-lift-type fermentor on autotrophic production
      of poly-(D-3-hydroxybutyric acid) [P(3HB)] by two-stage culture of Alcaligenes
      eutrophus is investigated. Addition of 0.05% CMC increased P(3HB) production rate
      during the P(3HB) accumulation phase to twice that of the control culture. It was
      thought that addition of a small amount of CMC was beneficial for production of
      P(3HB) employing the air-lift fermentor under safe autotrophic culture conditions
      in wich oxygen concentration was maintained below 6.9% (v/v). the volumetric mass
      transfer coefficient (K(L)a) observed in the presence of CMC is shown to
      correlated with the P(3HB) production rate obtained. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 53: 529-533, 1997.

PMID- 18634051
TI  - Myelodysplastic syndromes associated with interstitial deletion of chromosome 5q:
      clinicopathologic correlations and new insights from the pre-lenalidomide era.
AB  - To better estimate prognosis for patients with myelodysplastic syndromes (MDS)
      associated with clonal interstitial deletions of the long arm of chromosome 5
      (del(5q)), we reviewed the medical records of 130 adults with del(5q) MDS seen at
      our institution over a 15-year period. Overall median survival of this cohort was
      9.5 months, shorter than reported in earlier series. The least favorable outcomes
      are associated with complex cytogenetics, lack of any normal metaphases,
      normocytic rather than macrocytic erythrocyte indices, and low baseline
      lymphocyte counts. Lymphopenia but not neutropenia at the time of diagnosis
      appears to be a new adverse prognostic indicator. Cytogenetic breakpoints defined
      by G-banded karyotyping correlate poorly with particular disease features.
      Surprisingly, survival of patients with treatment-related MDS was equivalent to
      that of de novo MDS with del(5q) in this series. Morphologic features associated
      with del(5q) are diverse. Most patients with del(5q) MDS do not meet criteria for
      WHO-defined 5q-syndrome, and the presence of del(5q) does not appear to modify
      the clinical phenotype otherwise risk-stratified by the International Prognostic
      Scoring System (IPSS). Additional important prognostic factors not taken into
      account by the IPSS include the baseline erythrocyte indices, lymphocyte count,
      and clonal burden.

PMID- 18634052
TI  - Enhanced anti-cancer effect of a phosphatidylinositol-3 kinase inhibitor and
      doxorubicin on human breast epithelial cell lines with different p53 and
      oestrogen receptor status.
AB  - New efforts are being focused on signalling pathways as targets for cancer
      therapy. This particular study was designed to investigate whether blockade of
      the phosphatidylinositol 3OH-kinase (PI3K) pathway (a survival/anti-apoptosis
      pathway, overexpressed in various tumours) could sensitise human breast cancer
      cells to the effect of chemotherapeutics. Doxorubicin (Dox) and LY294002 (LY, a
      PI3K inhibitor) were used individually or in combination on MDA-MB-231 (p53
      mutant, ER-), T47D (p53 mutant, ER+), and MCF-7 (p53 wildtype, ER+) human breast
      cancer cell lines, and on 184A1, a nonmalignant human breast epithelial cell line
      (p53 wildtype, ER-). Each drug showed time- and dose-dependent growth inhibition
      of cell proliferation on all 4 cell lines. The combination of Dox+LY resulted in
      enhanced cell growth inhibition in MDA-MB-231 and T47D cells, and additive
      inhibition in MCF-7 and 184A1 cells. Cell cycle analysis showed that Dox+LY
      enhanced the arrest of MDA-MB-231 and T47D cells in G2 with the appearance of a
      sub-G1 peak indicating apoptosis/necrosis, a notion supported by enhanced
      depolarisation of mitochondrial membrane potential in these cell types. The
      combination also caused a greater additive increase in Cyclin B1. Thus, the
      synergistic effect of the combination on cell proliferation in some, but not all,
      breast cancer cells may be through enhanced induction of both G2 arrest and
      apoptosis, in which p53 may play a role. Substantially lower doses of doxorubicin
      could be used with low doses of inhibitors of the PI3K pathway, without
      compromising the anti-cancer effect, but also lowering detrimental side-effects
      of doxorubicin. This study supports the notion that survival signalling pathways
      offer special targets for chemotherapy in cancer.

PMID- 18634054
TI  - Toluene degradation kinetics for planktonic and biofilm-grown cells of
      Pseudomonas putida 54G.
AB  - Toluene degradation kinetics by biofilm and planktonic cells of Pseudomonas
      putida 54G were compared in this study. Batch degradation of (14)C toluene was
      used to evaluate kinetic parameters for planktonic cells. The kinetic parameters
      determined for toluene degradation were: specific growth rate, micro(max) = 10.08
      +/- 1.2/day; half-saturation constant, K(S) = 3.98 +/- 1.28 mg/L; substrate
      inhibition constant, K(I) = 42.78 +/- 3.87 mg/L. Biofilm cells, grown on ceramic
      rings in vapor phase bioreactors, were removed and suspended in batch cultures to
      calculate (14)C toluene degradation rates. Specific activities measured for
      planktonic and biofilm cells were similar based on toluene degrading cells and
      total biomass. Long-term toluene exposure reduced specific activities that were
      based on total biomass for both biofilm and planktonic cells. These results
      suggest that long-term toluene exposure caused a large portion of the biomass to
      become inactive, even though the biofilm was not substrate limited. Conversely,
      specific activities based on numbers of toluene-culturable cells were comparable
      for both biofilm and planktonically grown cultures. Planktonic cell kinetics are
      often used in bioreactor models to model substrate degradation and growth of
      bacteria in biofilms, a procedure we found to be appropriate for this organism.
      For superior bioreactor design, however, changes in cellular activity that occur
      during biofilm development should be investigated under conditions relevant to
      reactor operation before predictive models for bioreactor systems are developed.

PMID- 18634055
TI  - Overexpression of recombinant human antithrombin III in Chinese hamster ovary
      cells results in malformation and decreased secretion of recombinant protein.
AB  - Overexpression of recombinant proteins in animal cells is commonly achieved by
      using gene amplification techniques. Gene amplified cells possess up to several
      thousand genes coding for the target protein. Constitutive expression of these
      genes leads to high levels of the corresponding mRNA species and the immature
      protein in the cell. Inefficient processing of these precursors may result from
      their great abundance in the cell. To study the influence of elevated
      intracellular levels of a recombinant protein on its maturation and secretion, we
      examined the maturation and secretion of human antithrombin III (hATIII) in
      Chinese hamster ovary (CHO) cells at different levels of gene amplification. No
      loss of vitality was caused by elevated secretion of hATIII. As the intracellular
      hATIII content increased, the efficiency of hATIII secretion decreased steadily.
      The state of intracellular hATIII from the different cell lines was studied by
      determining the specific heparin cofactor activity of hATIII. Intracellular
      hATIII from the highest amplified cell line displayed a lowered specific heparin
      cofactor activity indicating the presence of malfolded, only partially folded, or
      incompletely or incorrectly posttranslationally modified hATIII in this cell
      line. Thus, the ability of CHO cells to fold and/or introduce posttranslational
      modifications and subsequently to secrete the recombinant protein becomes
      saturated, and therefore these processes may become limiting for protein
      secretion at highly elevated expression levels. This limitation was not due to a
      general exhaustion of the secretory capacity of the cells because hATIII
      constituted only a minor fraction of the secreted proteins, even at high
      expression levels.

PMID- 18634056
TI  - Feasibility of protein spray coating using a fluid-bed Wurster processor.
AB  - This article documents a feasibility study on coating fine powders with protein
      solutions using a Wurster spray coater (GPCG-1 from Glatt Air Techniques, Ramsey,
      NJ). Spray coating was based on a fluid-bed process where fluidized microcarriers
      were coated inside the Wurster column and dried in the fluidization chamber.
      Recombinant human deoxyribonuclease (rhDNase) was used as the model protein.
      Lactose powders of two different size ranges, 53-125 and 125-250 microm, were
      used as the model microcarrier. The amount of protein applied was varied to
      obtain coatings of varying thickness. The extent of rhDNase loading determined
      experimentally was found to be consistent with the theoretical value and was also
      confirmed visually by scanning electron microscopy. The coating showed a strong
      integrity after being subjected to mechanical force. However, the protein
      suffered serious aggregation during coating, most likely due to the thermal
      stress of the process. Aggregation was significantly reduced when rhDNase was
      formulated with calcium ions, consistent with the observation that Ca(2+)
      thermally stabilized the protein (as determined by scanning microcalorimetry) in
      aqueous solution. Thus, our study demonstrates that spray coating, particularly
      when used in conjunction with rational stabilization strategies, is a feasible
      alternative to other methods of preparing dried pharmaceutical proteins.

PMID- 18634057
TI  - Protein salting-out: phase equilibria in two-protein systems.
AB  - The phase behavior of two aqueous binary protein mixtures, lysozyme-chymotrypsin
      and lysozyme-ovalbumin, was determined in ammonium sulfate solutions. Protein
      concentrations were determined in both phases as a function of pH and ionic
      strength. For lysozyme-chymotrypsin mixtures, the observed phase behavior was
      similar to that for each individual protein; the presence of the second protein
      had little influence. The phase behavior of lysozyme-ovalbumin mixtures, however,
      was different from that of the respective single-protein systems. Lysozyme and
      ovalbumin are found together in egg whites; their association is both pH and
      ionic-strength dependent. The association of proteins is a key determinant of
      protein solubility in salt solutions.

PMID- 18634058
TI  - Process simulation for recombinant protein production: cost estimation and
      sensitivity analysis for heparinase I expressed in Escherichia coli.
AB  - Heparinase I from flavobacterium heparinum has several potential clinical
      applications; the resulting high demands on protein purity and quantity can be
      met by recombinant expression in Escherichia coli. Based on laboratory scale
      experiments with insoluble heparinase I expression followed by renaturation, a
      process for production of 3 kg/year of heparinase I was designed. We present a
      comparative analysis of the production costs of soluble and insoluble heparinase
      I expression, as well as a generalized approach to sensitivity analysis, based on
      perturbation around a base case design scenario. This may assist focusing further
      development on process steps for which improvements both are feasible and result
      in significant cost saving.

PMID- 18634059
TI  - Mechanism of protein extraction from the solid state by water-in-oil
      microemulsions.
AB  - The extraction of solid-phase alpha-chymotrypsin, bovine serum albumin (BSA), and
      lysozyme by water-in-oil microemulsion (w/o-ME) solution containing Aerosol-OT
      (AOT) was thoroughly examined as a means to maximize protein solubilization in
      organic solvent media. Protein extraction occurred simultaneously with the
      adsorption of water and AOT by the solid protein. Water and AOT were desorbed at
      nearly equal rates, suggesting that both materials were desorbed together as
      micreomulsions. The solubilization of protein increased linearly with the ratio
      of solid protein to extractant solution except at a high value of the ratio,
      where most protein-containing microemulsions were desorbed. Based on our results,
      a mechanistic model was developed to describe the solid-phase extraction
      procedure. First, microemulsions are desorbed from solution by the solid protein,
      resulting in the formation of a solid protein-AOT-water aggregate. Second, when a
      protein in the solid phase binds to a sufficient number of microemulsions, the
      resulting aggregate's increased hydrophobicity drives its solubilization into
      lipophilic solvent. Third, through the exchange of materials between the
      solubilized precipitate and the remaining microemulsions, protein-containing w/o
      MEs are formed. The presence of adsorption is further indicated by an isotherm
      existing between the water, AOT, and protein content of the resulting solid phase
      for each protein. The driving force behind adsorption is either AOT-protein
      interactions or the protein's affinity for microemulsion-encapsulated water,
      depending on the properties of the protein and the size of the microemulsions, in
      agreement with the model of P. L. Luisi [Chimia, 44: 270-282 (1990)]. The second
      step of our model is mass transfer limited for the extraction of solid alpha
      chymotrypsin and BSA. The extraction of solid lysozyme was limited by the
      occurrence of an irreversible precipitation process.

PMID- 18634060
TI  - Differential stability of proteolytically active and inactive recombinant
      metalloproteinase in Chinese hamster ovary cells.
AB  - Stability of heterologous protein expression during production is critical for
      regulatory approval of vaccine and therapeutic products. Leishmania GP63, a zinc
      metalloproteinase that is a potential vaccine candidate, has been expressed on
      the surface of Chinese hamster ovary (CHO) cells. Flow cytometry was used to
      follow the stability of GP63 expression. Expression of proteolytically active
      GP63 (GP63WT) was unstable whether or not methotrexate (MTX) selection was
      maintained. In contrast, expression of an active site mutant (GP63E265D) was
      stable under MTX selection. In the absence of selection, the decline in GP63E265D
      expression was more gradual than the loss of GP63WT expression. Different
      molecular mechanisms accounted for these losses and resulted in higher growth
      rate nonproducer populations. A dynamic population model was used to calculate
      the conversion rates of GP63WT producers to nonproducers.

PMID- 18634061
TI  - Continuous production of a hybrid antibiotic by Streptomyces lividans TK21
      pellets in a three-phase fluidized-bed bioreactor.
AB  - The continuous production of a hybrid antibiotic by a transformed strain of
      Streptomyces lividans TK21 in a three-phase fluidized bed is studied. Cell
      aggregates, known as pellets, are used as immobilized cell particles in the
      bioreactor. A methodology to prepare pellets of a suitable size and morphology is
      developed. The continuous production of the antibiotic is studied on the basis of
      decoupling cell growth and antibiotic production, by means of phosphate
      limitation in the growth medium. The best results are achieved at D = 0.021 h(1),
      with alternate feeding of 0 and 0.05 m M phosphate media. Continuous production
      of the antibiotic can be maintained at satisfactory levels for periods of 60
      days, and stable operation of the bioreactor is achieved during 85 days. Finally,
      the evolution of the internal structure of the pellets during continuous
      fermentation is studied.

PMID- 18634062
TI  - Factors affecting the fermentative production of a lysozyme-binding antibody
      fragment in Escherichia coli.
AB  - Fed-batch fermentation for production of a single-chain Fv antibody fragment
      (scFv) expressed as a recombinant periplastic protein from Escherichia coli was
      investigated. A high cell density of 50 g dry cell weight per liter was routinely
      achieved in a 14-L vessel by controlled exponential feeding of glucose to impose
      a constant specific growth rate. Following biomass accumulation, induction of the
      tac promoter by addition of IPTG was accompaied by a linear feed of yeast
      extract. The concentration of yeast extract feed was found to be highly
      influential upon both concentration and location of active product. Although scFv
      fragments were specifically targeted to the periplasmic space, at yeast extract
      feed rates of 0.72 g/h the final location was largely extracellular (68% to 79%).
      Total concentrations (extracellular + periplasmic) were of the order of 5 to 8
      mg/L. A ten-fold increase in yeast extract supply increased total scFv
      concentration to almost 200 mg/L and 78% of this yield was retained in the
      periplasm. Control of such leakage of the recombinant product is fundamental to
      process design of downstream operations for product recovery.

PMID- 18634063
TI  - Improved operational stability of cell-free glucose-fructose oxidoreductase from
      Zymomonas mobilis for the efficient synthesis of sorbitol and gluconic acid in a
      continuous ultrafiltration membrane reactor.
AB  - For the continuous, enzymatic synthesis of sorbitol and gluconic acid by cell
      free glucose-fructose oxidoreductase (GFOR) from Zymomonas mobilis, the principal
      determinants of productivity have been identified. Most important, the rapid
      inactivation of the soluble enzyme during substrate conversion can be avoided
      almost completely when weak bases such as tris(hydroxymethyl)aminomethan or
      imidazol are used for the titration of the produced gluconic acid and when 5-10
      mM dithiothreitol are added to prevent thiol oxidations. With regard to a long
      term operational stability of the enzyme for continuous syntheses, thermal
      deactivation becomes significant at reaction temperatures above 30 degrees C.
      Without any additional purification being required, the crude cell extract of Z.
      mobilis can be employed in a continuous ultrafiltration membrane reactor over a
      time period of more than 250 h without significant decrease in substrate
      conversion or enzyme activity. The use of soluble GFOR thus appears to be an
      interesting alternative to employing permeabilized cells of Zymomonas for the
      production of sorbitol and gluconic acid and may be superior with regard to
      reactor productivities, at comparable operational stabilities.

PMID- 18634064
TI  - Effects of alternative instrumentation strategies in adolescent idiopathic
      scoliosis: a biomechanical analysis.
AB  - The recent advent of modern instrumentation systems has improved the correction
      of scoliosis, but complicated the surgical decision-making process, especially
      with the introduction of diverse spinal fixation devices, new preoperative
      corrective maneuvers, and the reevaluation of many rules concerning the selection
      of fusion levels and other guidelines for surgical correction. Our objective was
      to assess the biomechanical effects of different instrumentation strategies for
      the same scoliotic cases. Several instrumentation strategies suggested by a group
      of 32 experienced senior surgeons for five cases were individually simulated
      using a validated computer model implemented in a spine surgery simulator. The
      resulting geometric indices varied among the five cases (e.g., range of main
      thoracic Cobb angles: 5-17 degrees , 16-29 degrees , 25-44 degrees , 15-34
      degrees , 16-32 degrees ; kyphosis: 22-33 degrees , 20-54 degrees , 33-55 degrees
      , 24-49 degrees , 29-46 degrees ; and lordosis: 10-52 degrees , 24-38 degrees ,
      26-54 degrees , 8-28 degrees , 34-53 degrees ). The average correction was better
      with pedicle screws (71%) than with hooks (51%) and hybrid constructs (67%). For
      the first time, to our knowledge, the effect of different instrumentation
      strategies was compared on the same patients, which is possible only with a
      surgery simulator. A large variability of instrumentation strategies existed
      among experienced surgeons and produced rather different results. This study
      questions the criteria for optimal configuration and standards to design the best
      surgical construct.

PMID- 18634065
TI  - The small GTPase Rho mediates articular chondrocyte phenotype and morphology in
      response to interleukin-1alpha and insulin-like growth factor-I.
AB  - Small GTPases regulate the cytoskeleton and numerous other cellular functions. In
      this study, the role of Rho GTPase was examined in articular chondrocytes.
      Chondrocytes grown in monolayer were treated with interleukin-1alpha (IL-1alpha),
      insulin-like growth factor-I (IGF-I), C3 Transferase, Y27632, or transfected with
      Rho wild type or two constitutively active mutants of Rho (Q63L and G14V).
      Quantitative PCR was used to determine changes in matrix metalloproteinase-13
      (MMP-13), collagen types IIB (COL2A1) and type I (COL1A1), aggrecan (AGG), and
      SOX-9 gene expression. Affinity assays were performed to measure endogenous GTP
      bound Rho, and confocal microscopy was used to assess changes in organization of
      the actin cytoskeleton. IL-1alpha and RhoG14V increased cytoplasmic actin stress
      fiber formation, which was blocked by C3 Transferase, and Y27632. IL-1alpha
      treatment also increased Rho activity. Conversely, IGF-I lead to formation of a
      cortical rim of actin and decreased Rho activity. Inhibition of Rho signaling
      with C3 Transferase significantly decreased Rho activity and returned IL-1alpha
      induced Rho activity to a level not different from control. C3 Transferase
      treatment also increased mRNA expression of AGG, COL2A1, and SOX-9, and decreased
      expression of MMP-13. Expression of RhoQ63L or RhoG14V resulted in increased MMP
      13 expression; however, inhibition of Rho with Y27632 was unable to inhibit IL
      1alpha-induced MMP-13 expression. Together, these results indicate a role for
      increased Rho activity in mediation of chondrocyte catabolic signaling pathways.

PMID- 18634067
TI  - Prevention of hybridoma cell death by bcl-2 during suboptimal culture conditions.
AB  - TB/C3 hybridoma cells were transected with either pEF-MClneopA or pEF bcl2
      MClneopA vectors to produce a control cell line (TB/C3 pEF) and a cell line that
      overexpresses the "antiapoptotic" human bcl-2 protein (TB/C3 bcl2). Flow
      cytometry analysis of intracellular bcl-2 protein levels enabled near on-line
      monitoring of the stability of bcl-2 expression in the absence of drug selection.
      It was possible to maintain spontaneous selection of cells with the
      overexpression of bcl-2 protein during semicontinuous cultures at very low
      dilution rates, where cells were subjected to the selective conditions of
      nutrient limitation and high toxic metabolite concentrations. Interestingly,
      cells that overexpressed bcl-2 were adapted to suspension culture conditions
      significantly faster than control cells. Dual fluorescence staining with acridine
      orange and propidium iodide allowed for discrimination between viable, apoptotic,
      secondary necrotic, and necrotic cells, respectively. Compared with the usual
      trypan blue method of establishing culture viability, dual staining demonstrated
      that under stressful conditions a significant proportion of cells that excluded
      trypan blue were also undergoing cell death through apoptosis. In batch cultures
      the overexpression of bcl-2 more than doubled the membrane intact (MI) cell
      productive period (the integral of Ml cell density with respect to culture time)
      and increased the monoclonal antibody (mAb) production by approximately 40% when
      compared with the control cell line. The overexpression of bcl-2 protein also
      significantly extended the cell integrity and viability by the suppression of
      apoptosis in conditions of hypoxia, hyperoxia, glutamine deprivation, glucose
      deprivation, and serum limitation. The suppression of apoptosis in anaerobic
      conditions suggests that bcl-2 exerts its antiapoptotic activity by a mechanism
      that does not involve an oxidative reactive pathway. In conditions of excess
      thymidine, which suppressed cell proliferation, Ml cell density and specific mAb
      productivity were further enhanced by the overexpression of bcl-2, which suggests
      the possibility of accomplishing a controlled proliferation in immortalized cell
      lines without invoking cell death. Cell size and intracellular mAb were increased
      for TB/C3 bcl2 cells compared with TB/C3 pEF control cells when analyzed by flow
      cytometry.

PMID- 18634066
TI  - In vivo effects of modification of hydroxyapatite/collagen composites with and
      without chondroitin sulphate on bone remodeling in the sheep tibia.
AB  - The addition of chondroitin sulphate (CS) to bone cements with calcium phosphate
      has lead to an enhancement of bone remodeling and an increase in new bone
      formation in small animals. The goal of this study was to verify the effect of CS
      in bone cements in a large animal model simulating a clinically relevant
      situation of a segmental cortical defect of a critical size on bone-implant
      interaction and bone remodeling. The influence of adding CS to
      hydroxyapatite/collagen (HA/Col) composites on host response was assessed in a
      standard sheep tibia model. A midshaft defect of 3 cm was created in the tibiae
      of 14 adult female sheep. The defect was filled with a HA/Col cement cylinder in
      seven animals and with a CS-modified hydroxyapatite/collagen (HA/Col/CS) cement
      cylinder in seven animals. In all cases the tibia was stabilized with an
      interlocked universal tibial nail. The animals in each group were analyzed with X
      rays, CT scans, histology, immunohistochemistry, and enzymehistochemistry, as
      well as histomorphometric measurements. The X-ray investigation showed a
      significantly earlier callus reaction around the HA/Col/CS implants compared to
      HA/Col alone. The amount of newly formed bone at the end point of the experiment
      was significantly larger around HA/Col/CS cylinders both in the CT scan and in
      the histomorphometric analysis. There were still TRAP-positive osteoclasts around
      the HA/Col implants after 3 months. The number of osteopontin-positive
      osteoblasts and the direct bone contact were significantly higher around
      HA/Col/CS implants. We conclude that addition of CS enhances bone remodeling and
      new bone formation around HA/Col composites.

PMID- 18634068
TI  - Effect of bench-scale culture conditions on murine IgG heterogeneity.
AB  - A stable murine hybridoma cell line, secreting IgG1 antibodies (7H3) against the
      soluble type I receptor for Tumor Necrosis Factor (sTNF-R1), was cultivated in
      two different bioreactor systems, a hollow fiber and a stirred tank fermentor, in
      order to evaluate the effect of culture conditions on antibody structural and
      functional heterogeneity. Conventional serum-supplemented and serum-free media
      were chosen for fermentation in stirred tank bioreactor, whereas only serum
      supplemented media were used for hollow fiber cultivation. Extent of
      glycosylation, determined by lectin binding assays, and charge heterogeneity of
      murine monoclonal antibodies displayed relevant variations according to the
      fermentation system used. After complete sugars removal by N-glycosidase F
      treatment, charge heterogeneity were still observed suggesting the occurrence of
      additional modifications at the protein level. In vitro culture in serum
      supplemented media carried out with the hollow fibre system led to higher
      productivity but greater antibody charge heterogeneity and differences in lectin
      binding profile than cultivation in the stirred tank bioreactor.Results
      cumulatively indicated that hybridoma cultivation methods, but also cultivation
      time, influence antibody heterogeneity, both in the protein and sugar moieties.

PMID- 18634069
TI  - Design of surfactants suitable for protein extraction by reversed micelles.
AB  - New surfactants have been synthesized for potential use in reversed micellar
      protein extraction operations. Preferential solubility of the surfactant in an
      aliphatic solvent such as hexane, heptane, or isooctane and the formation of
      reversed micelles accompanied with solubilization of significant quantities of
      water can be achieved by using strongly hydrophobic, twin alkyl chains as the
      hydrophobic moiety. Different surfactants having identical water-solubilizing
      capacities can have significantly different behavior in protein extractions,
      where extraction efficiency appears to be governed by the nature of the
      interfacial complex that forms between surfactants and proteins. Bulky surfactant
      chains provide a steric hindrance to the adsorption of the surfactant to the
      protein surface, thus inhibiting solvation of the protein/surfactant complex, and
      hence protein extraction. Under these conditions, a precipitate forms either in
      the bulk aqueous phase or at the interface. Surfactants that can form a close
      packed complex with the protein are excellent protein-solubilizing agents.
      Dioleyl phosphoric acid (DOLPA) appears to be the best surfactant currently
      available for protein extraction.

PMID- 18634070
TI  - Trehalase immobilization on aminopropyl glass for analytical use.
AB  - Trehalase is the enzyme which hydrolyzes the disaccharide trehalose into two
      alpha-D-glucose molecules. In this article, we present the immobilization of
      trehalase on aminopropyl glass particles. The enzyme was extracted from
      Escherichia coli Mph2, a strain harboring the pTRE11 plasmid, which contains the
      trehalase gene. The partially purified enzyme had a specific activity of 356 U/mg
      and could be used for quantifying trehalose in the presence of sucrose, maltose,
      lactose, starch, and glycogen. Partially purified trehalase was immobilized by
      covalent coupling with retention of its catalytic activity. The support chosen
      for the majority of the experiments reported was aminopropyl glass, although
      spherisorb-5NH(2) and chitin were also tested. The immobilized enzyme was assayed
      continuously for 40 h, at pH 6.0 and 30 degrees C, and no release of enzyme
      molecules was detected during this procedure. The best condition found for
      storing the enzyme-support complex was at 4 degrees C in the presence of 25 mM
      sodium maleate, containing 7 mM beta-mercaptoethanol, 1 mM
      ethylenediaminetetraacetic acid (EDTA), and 50% glycerol. The enzyme under these
      conditions was stable, retaining approximately 100% of its initial activity for
      at least 28 days. The immobilized enzyme can be employed to detect trehalose
      molecules in micromolar concentration. The optimum pH value found was 4.5 and the
      K(m) app. 4.9 x 10(-3) M trehalose at pH 4.6 and 30 degrees C, with V(max) of
      5.88 micromol glucose x min x(-1), as calculated by a Lineweaver-Burk plot.

PMID- 18634071
TI  - Preliminary characterization of bovine beta-lactoglobulin after its conjugation
      to polyethylene glycol.
AB  - The major component of the whey fraction of bovine milk, beta-lactoglobulin
      (betaLG), has been transformed by grafting polyethylene glycol chains either on
      the thiol group (free and after reduction of the S-S bridges) of the cysteine
      residues, or on the amino group of the lysine residues and/or of the N-terminal
      amino acid. Acylation of the protein was achieved at a controlled pH of 7.0 using
      increasing ratios of activated PEG to betaLG. Transformation of the dimeric form
      into the monomer occurred at least for the fully pegylated adduct. The number of
      polymer chains fixed per mole of protein was determined by dosage of the free
      amino functions still present after reaction. The incidence of pegylation on the
      secondary structure of betaLG was evaluated using the Fourier Transform Infrared
      Spectroscopy (FTIR). Denaturation studies with guanidinium hydrochloride (Gu-HCl)
      by means of spectrofluorimetric measurements, showed an identical behavior of
      native as well as of pegylated betaLG.The antigenicity of the fully pegylated
      adduct was examined through antigenic competition towards native betaLG. The
      pegylated protein exhibited less than 1/100 of the native betaLG inhibition
      capacity, that could moreover never be complete. This is thus demonstrating the
      loss of accessibility for at least multiple conformational epitopes through
      pegylation procedure.Spectrofluorimetric measurements showed that betaLG-N-PEG(7)
      was still able to bind retinol while no effect on the intrinsic fluorescence
      could be detected by adding palmitic acid. Whether this last ligand binds or not
      to pegylated betaLG is discussed.

PMID- 18634072
TI  - Activity, stability, and conformation of methoxypoly(ethylene glycol)-subtilisin
      at different concentrations of water in dioxane.
AB  - The transesterification activity, autolysis, thermal stability and conformation
      of subtilisin Carlsberg, made soluble in dioxane by covalent linking to
      methoxypoly(ethylene glycol) (PEG), were investigated as a function of the
      concentration of water in the medium. Electrospray mass spectrometry showed that
      the modified enzyme preparation was a mixture of proteins containing from 2 to 5
      covalently linked PEG chains per subtilisin molecule. PEG-subtilisin catalyzed
      transesterification between vinyl butyrate and 1-hexanol was optimum at 0.55
      MH(2)O, while hydrolysis prevailed above 2 MH(2)O. There was a decrease in the
      overall enzyme activity with increasing water concentration because of autolysis
      and denaturation of the enzyme. Subtilisin powder and celite-immobilized
      subtilisin were more stable and less susceptible to autolysis than the PEG
      modified enzyme. Circular dichroism and intrinsic protein-fluorescence studies
      showed that the conformation of PEG-subtilisin did not change as a function of
      water concentrations between 0 and 9 M. The K(m,app) value of PEG-subtilisin for
      1-hexanol was highly influenced by water, which behaved as a competitive
      inhibitor in the transesterification reaction with an affinity for the enzyme
      similar to that of the alcohol. The K(m,app) for the acylating agent was not
      significantly modified by water. Lyoprotectants such as sorbitol and free PEG did
      not influence the activity of PEG-subtilisin but notably increased the activity
      of subtilisin powder and celite-immobilized subtilisin. The addition of 1.7-5.5 M
      water, however, rendered enzyme preparations containing no additives as active as
      those containing the lyoprotectants.

PMID- 18634073
TI  - Cellular determinants affecting the rate of cytokine in cultures of human
      hematopoietic cells.
AB  - The present study was undertaken to define parameters that may limit the cytokine
      mediated expansion of primitive hematopoietic cells in stirred suspension
      cultures of normal human marrow cells. In a first series of experiments, parallel
      measurements of the rate and extent of progenitor expansion and cytokine
      depletion from the medium were made for such cultures in which the cells were
      exposed to different cytokine concentrations. Supplementation of the medium with
      2 ng/mL of interleukin-3 (IL-3), IL-6 and IL-11 plus 10 ng/mL of Flt-3 ligand
      (FL) and Steel factor (SF) allowed a 45-fold expansion of directly clonogenic
      cell (CFC) numbers within 2 weeks along with a 2.5-fold expansion of their
      precursors, detectable as longterm culture-initiating cells (LTC-IC). The
      addition of 5-fold higher levels of these cytokines enhanced the 2 week output of
      both CFC and LTC-IC numbers (to 66-fold and 9-fold above input respectively).
      However, this was also associated with an increase in the individual average
      rates of depletion of immunoreactive IL-3, SF and FL. As a result, even biweekly
      addition of fresh medium supplemented with the highest concentrations of
      cytokines tested failed to prevent a continuing decline in their levels relative
      to the input medium levels. A similar dependence of the IL-3 depletion rate on
      its extracellular concentration was demonstrable in suspension cultures of Mo7e
      cells, an IL-3-dependent human leukemic cell line.Additional experiments with
      various highly purified marrow cell fractions showed that the rate of cytokine
      depletion varied according to the type of responding cell as well as the specific
      cytokine. CD34(+)CD38(-) cells exhibited the greatest average cell-specific
      cytokine depletion rates (35-fold higher than unseparated bone marrow cells).
      These findings establish new principles that will be important for the
      optimization of hematopoietic cell bioreactors. In addition, they suggest that
      cytokine depletion may provide a novel feedback control mechanism in vivo which
      would contribute to the control of primitive hematopoietic cell proliferation and
      differentiation.

PMID- 18634074
TI  - How do additives affect enzyme activity and stability in nonaqueous media?
AB  - The catalytic activities of lyophilized powders of alpha-chymotrypsin and Candida
      antarctica lipase were found to increase 4- to 8-fold with increasing amounts of
      either buffer salts or potassium chloride in the enzyme preparation. Increasing
      amounts of sorbitol in the chymotrypsin preparation produced a modest increase in
      activity. The additives are basically thought to serve as immobilization
      matrices, the sorbitol being inferior because of its poor mechanical properties.
      Besides their role as supports, the buffer species were indispensable for the
      transesterification activity of chymotrypsin because they prevented perturbations
      of the pH during the course of the reaction. Hence, increasing amounts of buffer
      species yielded a 100-fold increase in transesterification activity. Effects of
      pH changes were not as predominant in the peptide synthesis and the lipase
      catalyzed reactions. Immobilization of the protease on celite resulted in a
      remarkable improvement of transesterification activity as compared to the
      suspended protease, even in the absence of buffer species. Immobilization of the
      lipase caused a small improvement of activity. The activity of the immobilized
      enzymes was further enhanced 3-4 times by including increasing amounts of buffer
      salts in the preparation.The inclusion of increasing amounts of sodium phosphate
      or sorbitol to chymotrypsin rendered the catalyst more labile against thermal
      inactivation. The denaturation temperature decreased with 7 degrees C at the
      highest content of sodium phosphate, as compared to the temperature obtained for
      the denaturation of the pure protein. The apparent enthalpy of denaturation
      increased with increasing contents of the additives. The enhancement of hydration
      level and flexibility of the macromolecule upon addition of the compounds partly
      provides the explanation for the observed results.

PMID- 18634075
TI  - Microbial growth on substitutable substrates: characterizing the consumer
      resource relationship.
AB  - In this article, we consider the growth of microorganisms on mixtures of carbon
      sources and characterize the consumer-resource relationship for this system. The
      characteristic features observed for the growth of a single microorganism on a
      pair of carbon sources allow a representation of this relationship based on a
      general paradigm for resource classification. This representation is verified
      using a comprehensive model for microbial growth on carbon sources. The results
      show that for the same pair of carbon sources the qualitative nature of the
      consumer-resource relationship changes with changing specific growth rate, and
      therefore a change in the identity of the rate-limiting substrate(s).

PMID- 18634076
TI  - Anti-histones antibodies in systemic lupus erythematosus: prevalence and
      frequency in neuropsychiatric lupus.
AB  - To investigate the specificity, sensitivity, and concomitant presence of
      antibodies against histones (H), histone H1 (H1), and histone H3 (H3) in patients
      with systemic lupus erythematosus (SLE) and analyze their association with SLE.
      Serum IgG anti-histones antibodies were detected by enzyme-linked immunosorbent
      assay in 144 SLE patients consisting of 24 neuropsychiatric lupus (NPSLE), 65
      lupus nephritis (LN), and 55 SLE, 100 other rheumatic diseases patients, as well
      as 40 healthy controls. Clinical and biological parameters of the patients were
      also evaluated. Anti-H, anti-H1, and anti-H3 antibodies yielded a sensitivity of
      approximately 33% and a specificity of more than 93% for SLE, which was
      comparable to that found for anti-double-stranded DNA (anti-dsDNa) antibodies.
      More significantly, anti-histone antibody is found in approximately 50% of
      patients with NPSLE compared with LN. Moreover, the titers of anti-histones
      antibodies of NPSLE patients were significantly higher than that of patients with
      SLE and LN. The sequential analysis revealed a close correlation of anti-H and
      anti-H1 antibodies with SLE disease activity. There was an approximate 30%
      positive rate of anti-histones antibodies in 144 SLE patients lacking anti
      nucleosome, anti-mDNA, anti-Sm, and anti-dsDNA antibodies. Antibodies to histones
      H1 and H3 are markers with high specificity of 93.6-96.4% for SLE. The anti
      histone antibody markers are prevalent in approximately 50% of NPSLE.
      Furthermore, there was a strong correlation with SLE disease activity index and
      levels of antibodies to histones and H1.

PMID- 18634077
TI  - Effects of spatiotemporal variations on metabolic control: approximate analysis
      using (log)linear kinetic models.
AB  - For many metabolic systems, available experimental data allow description of the
      system by elasticities and control coefficients. The availability of information
      of this kind motivated the development of a (log)linear kinetic model of
      metabolic systems that is completely and explicitly determined by this
      information. It is shown here that this model can accurately describe the dynamic
      responses of metabolic systems that exhibit strong nonlinearities. Based on the
      excellent approximation provided by the (log)linear model, a method is developed
      for the estimation of the performance of metabolic systems subject to
      spatiotemporal variations of the system parameters and the process operating
      conditions. The method suggests experiments that can quantify the effect of these
      variations. Study of a model glycolytic pathway illustrates the applicability and
      the usefulness of this framework. Time-average flux control coefficients are
      shown to vary strongly and not monotonically as the period of the external
      variations changes.

PMID- 18634078
TI  - Dramatically stabilized phosphotriesterase-polymers for nerve agent degradation.
AB  - Phosphotriesterase (EC 3.1.8.1) was immobilized within a polyurethane foam matrix
      during polymer synthesis using a prepolymer synthesis strategy. In addition to
      retaining greater than 50% of the enzyme specific activity, numerous benefits
      were incurred upon immobilization. Orders of magnitude increases in storage and
      thermal stability (net stabilization energy = 12.5 kJ/mol) were observed without
      the need for enzyme premodification. The immobilized enzyme system was protease
      resistant and seemed to display no adverse effects from immobilization, such as
      an alteration of enzyme function. The organic solvent, dimethyl sulfoxide, also
      exhibited a stabilizing effect on phosphotriesterase enzyme systems over a range
      of intermediate concentrations. We attribute these effects in part to direct
      interaction between the aprotic solvent and metal containing residues present at
      the enzyme's active site. Our data demonstrate that just 2.5 kg of immobilized
      enzyme may be sufficient to degrade 30,000 tons of nerve agent in just 1 year.

PMID- 18634079
TI  - Production of a high viscosity polysaccharide, methylan, in a novel bioreactor.
AB  - The effect of shear stress on the production of a high viscosity polysaccharide,
      methylan, from methanol by Methylobacterium organophilum was investigated by
      using a multidisk mixer. It was observed in the multidisk mixer with defined
      shear stresses that the specific production rate of methylan increased gradually
      with increasing shear stress up to 30 Pa, and the production rate was constant
      beyond 30 Pa. This result suggested that the limited mass transfer from the
      medium into cells reduced methylan production. A novel bioreactor that provided
      the large volume of a high shear region was used to increase methylan production.
      Fed-batch cultures in the novel bioreactor were performed by the dissolved oxygen
      stat method of methanol. When 1.13 g/L ammonium ion was added, the concentrations
      of cells of methylan were 31 and 20.6 g/L, respectively. The productions of cells
      and methylan in our designed bioreactor were 20 and 50% higher than those
      obtained in a conventional fermentor. The methylan content reached a maximum of
      20.7 g/L in the bioreactor and the viscosity of the fermentation broth was 127 Pa
      . s, which corresponds to 68 g/L as a xanthan.

PMID- 18634080
TI  - Modeling and analysis of layered stationary anaerobic granular biofilms.
AB  - A model that portrays substrate profiles in a steady-state multispecies granular
      biofilm is developed and coupled with a biofilm detachment model. The model
      accounts for glucose, propionate, hydrogen, and acetate transformations performed
      by three bacterial trophic groups: acidogens, syntrophic bacterial consortia, and
      methanogens. This model adequately describes the phenomenon of propionate
      degradation under thermodynamically unfavorable bulk hydrogen concentrations.
      Also suggested is the superiority of the layered biofilm structure over
      homogeneous distribution of the trophic groups for anaerobic degradation of
      organic compounds. Furthermore, model analysis suggests that with increasing bulk
      glucose concentration biofilm thickness reaches a maximum that is then followed
      by biofilm disintegration. These results may have an important impact on the
      design and control of upflow anaerobic sludge bed reactors.

PMID- 18634081
TI  - Activity of Toluene-degrading Pseudomonas putida in the early growth phase of a
      biofilm for waste gas treatment.
AB  - A biological trickling filter for treatment of toluene-containing waste gas was
      studied. The overall kinetics of the biofilm growth was followed in the early
      growth phase. A rapid initial colonization took place during the first three
      days. The biofilm thickness increased exponentially, whereas the incease of
      active biomass and polymers was linear. In order to investigate the toluene
      degradation, various toluene degraders from the multispecies biofilm were
      isolated, and a Pseudomonas putida was chosen as a representative of the toluene
      degrading population. A specific rRNA oligonucleotide probe was used to follow
      the toluene-degrading P. putida in the multispecies biofilm in the filter by
      means of number and cellular rRNA content. P. putida appeared to detach from the
      biofilm during the first three days of growth, after which P. putida was found at
      a constant level of 10% of the active biomass in the biofilm. Based on the rRNA
      content, the in situ activity was estimated to be reduced to 20% of cells grown
      at maximum conditions in batch culture. The toluene degraded by P. putida was
      estimated to be a minor part (11%) of the overall toluene degradation.

PMID- 18634082
TI  - Effect of elevated oxygen and glutamine levels on foreign protein production at
      high cell densities using the insect cell-baculovirus expression system.
AB  - Per cell protein expression in virally-infected insect cells declines
      significantly at high cell density resulting in a decrease in volumetric
      productivity. Specific protein expression levels in Spodoptera frugiperda (Sf-21)
      cells could be increased at high cell densities by increasing the oxygen supply
      and by supplementing the medium with glutamine post-infection. beta-Galactosidase
      yield was increased from 411 to 855 IU/ml by increasing the glutamine
      concentration in the medium by 46% and increasing the gas phase oxygen
      concentration from 21 to 80%. Similarly, the yield of a secreted alkaline
      phosphatase was increased from 14.2 to 26.2 IU/mL using the same conditions. Part
      of the increase in production with Sf-21 culture was due to increased release to
      the extra-cellular compartment at the higher oxygen concentrations. Increasing
      the gas phase oxygen concentration to 95% in conjunction with a 100% increase in
      glutamine and glucose concentrations did not improve the yield any further. Peak
      production under elevated oxygen and nutrient conditions occurred at 72 h about
      24-48 h earlier than under normal conditions. In a Trichoplusia ni cell line (BTI
      TN-5B1-4), the maximum secreted alkaline phosphatase activity was increased from
      10 to 27.2 IU/mL by similarly manipulating the oxygen supply.

PMID- 18634083
TI  - The effect of dissolved oxygen on the metabolic profile of a murine hybridoma
      grown in serum-free medium in continuous culture.
AB  - The murine B-lymphocyte hybridoma, CC9C10 was grown at steady state under serum
      free conditions in continuous culture at dissolved oxygen (DO) concentrations in
      the range of 10% to 150% of air saturation. Cells could be maintained with this
      range at high viability in a steady state at a dilution rate of 1 d(-1), although
      with lower cell concentrations at higher DO. A higher specific antibody
      production measured at higher DO was matched by a decrease in the viable cell
      concentration at steady state, so that the volumetric antibody titre was not
      changed significantly. An attempt to grow cells at 250% of air saturation was
      unsuccessful but the cells recovered to normal growth once the DO was
      decreased.There was a requirement for cellular adaptation at each step-wise
      increase in dissolved oxygen. Adaptation to a DO of 100% was associated with an
      increase in the specific activities of glutathione peroxidase (x18), glutathione
      S-transferase (x11) and superoxide dismutase (x6) which are all known antioxidant
      enzymes. At DO above 100%, the activities of GPX and GST decreased possibly as a
      result of inactivation by reactive oxygen radicals.The increase in dissolved
      oxygen concentration caused changes in energy metabolism. The specific rate of
      glucose uptake increased at higher dissolved oxygen concentrations with a higher
      proportion of glucose metabolized anaerobically. Short-term radioactive assays
      showed that the relative flux of glucose through glycolysis and the pentose
      phosphate pathway increased whereas the flux through the tricarboxylic acid cycle
      decreased at high DO. Although the specific glutamine utilization rate increased
      at higher DO, there was no evidence for a change in the pattern of metabolism.
      This indicates a possible blockage of glycolytic metabolites into the TCA cycle,
      and is compatible with a previous suggestion that pyruvate dehydrogenase is
      inhibited by high oxygen concentrations.Analysis of the oxygen uptake rate of
      cell suspensions at steady state under all conditions showed a pronounced
      Crabtree effect which was manifest by a decrease (up to 40%) in oxygen
      consumption on addition of glucose. This indicates that the degree of aerobic
      metabolism in these cultures is highly sensitive to the glucose concentration.

PMID- 18634084
TI  - Effect of serum-free and serum-containing medium on cellular levels of ER-based
      proteins in various mouse hybridoma cell lines.
AB  - BiP, GRP94 and PDI, three endoplasmic reticulum (ER) based proteins are involved
      in the maturation of secretory proteins and might represent a bottleneck in the
      secretory pathway of monoclonal antibodies (MAB). With the three hybridoma cell
      lines tested, MAB production kinetics were significantly increased for the batch
      cultures done in serum-free medium (SFM) with respect to those done in serum
      containing medium (SCM). It could be established that there was a correlation
      between the cellular levels of PDI and GRP94 and the specific MAB production
      rate. With respect to BiP, no correlation with the MAB production rate was
      observed. The non-producing myeloma cell line X63, used as a reference, showed
      increased cellular PDI levels when cultivated in SFM. However, in this cell, the
      cellular GRP94 levels were not significantly influenced by the medium
      composition.It was concluded that SFM induced an increase of cellular PDI levels
      and this elevation seemed to be responsible for the increase in the specific MAB
      production rates. On the other hand, only MAB producing cells showed an increase
      in the cellular GRP94 levels which might be a result of increased MAB sythesis.
      Indeed, I.13.17 cultivated in SFM supplemented with serum showed a significantly
      reduced (about 50%) specific MAB production rate in comparison to I.13.17
      cultivated in non-serum supplemented SFM. The cellular PDI and BiP levels did not
      vary between these conditions of culture, whereas the cellular GRP94 level was
      about two-fold lower in I.13.17 cultivated in SFM when supplemented with serum
      than in I.13.17 cultivated in SFM without futher supplementation. These results
      are discussed with respect to the medium composition as well as in the context of
      apparent and potential bottlenecks within the secretory pathway of MAB.

PMID- 18634085
TI  - Plasma protein fractionation with advanced membrane adsorbents.
AB  - High capacity membrane adsorbents have been used as a stationary phase for the
      preparative chromatographic purification of human serum albumin. A two-step ion
      exchange fractionation scheme yields albumin with 98% purity from clarified,
      microfiltrated, and desalted human plasma. Experiments with laboratory and pilot
      scale membrane modules are compared to literature data obtained with conventional
      Fast Flow Sepharose in a similar purification protocol. Increased productivity in
      combination with excellent reproducibility and stability was found using the
      membrane adsorbents. Scale-up of the process based on standard microfiltration
      equipment was successful but resulted in reduced capacity and productivity due to
      deteriorated flow characteristics of the module. This was attributed to the
      effects of substantial axial dispersion in the pilot scale module. Methods to
      reduce this limitation were identified. The concept of membrane adsorption
      chromatography for the fast purification of proteins is illustrated and
      engineering aspects important for the process design are discussed.

PMID- 18634086
TI  - Inducing single-cell suspension of BTI-TN5B1-4 insect cells: I. The use of
      sulfated polyanions to prevent cell aggregation and enhance recombinant protein
      production.
AB  - Sulfated polyanions have been successfully used to rapidly obtain and maintain
      stable single-cell suspension of BTI-TN5B1-4 cells, a cell line which has a high
      intrinsic capacity for recombinant protein production but clumps severely in
      suspension reducing its effectiveness as a host for foreign protein production
      with the baculovirus expression vector system. The efficacy of inducing single
      cell suspension correlated positively with the increase in sulfation of the added
      polyanion. Unsulfated polyanions, neutral polymers, polycations, disaccharides,
      and monosaccharides were ineffective in inducing single-cell
      suspension.Elimination of clumping in suspension culture by adding a dispersing
      agent can lead to enhanced recombinant protein production. Inducing single-cell
      suspension with dextran sulfate, a highly sulfated polyanion, resulted in a four
      fold increase in volumetric yield of the recombinant glycosylated protein, human
      secreted alkaline phosphatase, and a two-fold increase in volumetric yield of the
      recombinant cytoplasmic protein, beta-galactosidase. High yields of 82 U/ml (ca.
      110 mg/L) for alkaline phosphatase, and 705 U/mL (ca. 2.3 g/L) for beta
      galactosidase under elevated oxygen have been obtained. The optimum volumetric
      yield of alkaline phosphatase in BTI-TN5B1-4 dextran sulfate cells under elevated
      oxygen but unsupplemented medium is 6 to 11-fold higher than attached cultures,
      and 3-fold higher than the best yield obtained for SF21 cells in suspension at
      elevated oxygen and with nutrient supplementation. More importantly, cells can be
      infected at high density without complications from aggregation, which has
      important implications for scale-up.

PMID- 18634087
TI  - Inducing single-cell suspension of BTI-TN5B1-4 insect cells: II. The effect of
      sulfated polyanions on baculovirus infection.
AB  - Sulfated polyanions can be used to rapidly induce and maintain single-cell
      suspensions of BTI-TN5B1-4 insect cells, a cell line which clumps in suspension.
      Elimination of cell clumping results in a significant increase in volumetric
      yield of the baculovirus expression vector system. Sulfated polyanions, however,
      inhibited baculovirus infection of BTI-TN5B1-4. Data from binding studies and
      fusion assays suggest that the inhibition of infection was not due to the
      observed reduction in viral attachment rate but to inhibition of viral membrane
      fusion in the endosome.The three most effective polyanions for inducing single
      cells are dextran sulfate, pentosan sulfate, and polyvinyl sulfate. At
      concentrations required for single-cell formation, dextran sulfate and pentosan
      sulfate did not affect viral infection at multiplicities of infection greater
      than one plaque forming unit per cell. In contrast, polyvinyl sulfate blocked
      viral infection even at a high multiplicity of infection of 20 plaque-forming
      units per cell. To bypass this inhibition, polyvinyl sulfate can be removed by
      resuspending the cells in fresh medium before virus addition, and then added back
      to the cell suspension after a substantial amount of virus has been internalized.
      Alternatively, polyvinyl sulfate can be neutralized with a polycation before
      virus addition, and an equivalent amount of polyvinyl sulfate added back after
      most of the virus has been internalized. We present a simple mathematical model
      of the attachment and entry of baculovirus in BTI-TN5B1-4, which can be used to
      design appropriate infection regimens.

PMID- 18634088
TI  - Oxidative renaturation of lysozyme at high concentrations.
AB  - Newly synthesized cloned gene proteins expressed in bacteria frequently
      accumulate in insoluble aggregates or inclusion bodies. Active protein can be
      recovered by solubilization of inclusion bodies followed by renaturation of the
      solubilized (unfolded) protein. The recovery of active protein is highly
      dependent on the renaturation conditions chosen. The renaturation process is
      generally conducted at low protein concentrations (0.01-0.2 mg/mL) to avoid
      aggregation. We have investigated the potential of successfully refolding reduced
      and denatured hen egg white lysozyme at high concentrations (1 and 5 mg/mL). By
      varying the composition of the renaturation media, optimum conditions which
      kinetically favor proper folding over inactivation were found. Solubilizing
      agents such as guanidinium chloride (GdmCl) and folding aids such as L-arginine
      present in low concentrations during refolding effectively enhanced renaturation
      yields by suppressing aggregation resulting in reactivation yields as high as
      95%. Quantitatively the kinetic competition between lysozyme folding and
      aggregation can be described using first-order kinetics for the renaturation
      reaction and third-order kinetics for the overall aggregation pathway. The rate
      constants for both reactions have been found to be strongly dependent on
      denaturant and thiol concentration. This strategy supercedes the necessity to
      reactivate proteins at low concentrations using large renaturation volumes. The
      marked increase in volumetric productivity makes this a viable option for
      recovering biologically active protein efficiently and in high yield in vitro
      from proteins produced as inclusion bodies within microbial cells.

PMID- 18634089
TI  - High frequency production of embryos from liquid flask cultures of oilseed rape.
AB  - As part of the program to scale-up the production of artificial seeds of winter
      oilseed rape, Brassica napus ssp. oleifera, we established a liquid flask culture
      system that enables the high frequency production of freely suspended embryos. As
      many as 4000 embryos could be obtained from 1 mL packed-cell-volume of cells. For
      initiation of liquid flask cultures, four different types of callus tissues were
      used. Among them, the most embryogenic cell suspension cultures were obtained
      from spontaneous callus developed on the surface of secondary embryos precultured
      in medium supplemented with 2,4-dichlorophenoxyacetic acid (4.52 microM) and
      kinetin (0.46 microM) (type B callus). Growth curves of the cell suspension were
      determined and the cell suspension was able to grow in medium without plant
      growth regulators. Embryos were observed to developed directly from the cells
      without going through an obvious callus phase. When subcultured to agar medium
      containing 44.38 microM benzylaminopurine, about 43% of the embryos developed
      into plants.

PMID- 18634090
TI  - A novel dielectrophoresis-based device for the selective retention of viable
      cells in cell culture media.
AB  - Cost-effective production of biopharmaceuticals on a large scale can be carried
      out by perfusion cultures of mammalian cells. One problem with this mode of
      operation for submerged free-cell cultures is the requirement for an efficient
      cell separation device located in the effluent stream. The present work
      investigates the potential for the development of a novel dielectrophoresis-based
      cell separator, capable of providing selective retention of viable cells in cell
      culture media, which are highly conductive. Predictions of the dielectrophoretic
      (DEP) response in culture media were first obtained through a series of DEP
      levitation experiments. Subsequently, a prototype microelectrode "filter" was
      microfabricated and tested with C174 myeloma cell suspensions of density 1 x
      10(6) cells/mL. The optimum frequency range for selective retention of viable
      cells was found in the range 5-15 MHz. A maximum separation efficiency of 98% was
      achieved at 10 MHz, with an applied peak-to-peak voltage of 30 V (maximum field
      strength of 10(5) V/m) and a flow rate of 30 mL/h which corresponds to a
      superficial velocity of 5.23 cm/h through the DEP-filter channels.

PMID- 18634091
TI  - Model development for horseradish peroxidase catalyzed removal of aqueous phenol.
AB  - Once activated by hydrogen peroxide, horseradish peroxidase (HRP) catalyzes the
      oxidation of aqueous aromatic compounds to produce high molecular weight polymers
      of low solubility. A pseudo steady-state kinetic model of the HRP-hydrogen
      peroxide-aromatic compound system was modified to incorporate enzyme inactivation
      mechanisms in order to improve its predictive ability. The kinetic constants of
      the model were calibrated using a series of experimental data sets. The model's
      ability to predict the time-dependent removal of phenol within the range of 0.5-6
      mM from a batch reactor was validated. The model accounts for permanent losses of
      enzyme activity through inactivation by free radicals as well as interaction with
      end-product polymers as they form.

PMID- 18634092
TI  - Cell cycle dependency of rice alpha-amylase production in a recombinant yeast.
AB  - The cell cycle dependency of rice alpha-amylase production in Saccharomyces
      cerevisiae was investigated using synchronous and arrested cultures. The results
      of two separate synchronous cultures, using alpha-mating factor and a cdc28
      mutant, indicated that the rice alpha-amylase-specific production rate is not
      constant during the cell cycle. The specific production rates during G1, S, and M
      phases were then ascertained by inhibiting the progression of the cell cycle
      using alpha-mating factor, hydroxyurea, and nocodazole, respectively. The
      specific production rate was found to be maximal during the M phase. The increase
      in the specific production rate during the M phase was confirmed from the
      accumulation of M-phase cells using a cdc15 mutant. The intracellular content of
      rice alpha-amylase was also measured during the cell cycle. Like the specific
      production rate, the intracellular content was found to fluctuate throughout the
      cell cycle, and to reach a maximum during M phase.

PMID- 18634093
TI  - Effects of glutamine supply on growth and metabolism of mammalian cells in
      chemostat culture.
AB  - Glutamine is a major source of energy, carbon, and nitrogen for mammalian cells.
      The amount of glutamine present in commercial mammalian cell media is, however,
      not necessarily balanced with cell requirements. Therefore, the effects of
      glutamine limitation on the physiology of two mammalian cell lines were studied
      in steady-state chemostat cultures fed with IMDM medium with 5% serum. The cell
      lines used were MN12, a mouse-mouse hybridoma, and SP2/0-Ag14, a mouse myeloma
      often used in hybridoma fusions. Cultures, grown at a fixed dilution rate of 0.03
      h(-1), were fed with media containing glutamine concentrations ranging from 0.5
      to 4 mmol L(-1). Biomass dry weight and cell number were linearly proportional to
      the glutamine concentrations fed, between 0.5 and 2 mmol L(-1), and glutamine was
      completely consumed by both cell lines. From this it was concluded that glutamine
      was the growth-limiting substrate in this concentration range and that the
      standard formulation of IMDM medium contains a twofold excess of glutamine. In
      glutamine-limited cultures, the specific rates of ammonia and alanine production
      were low compared to glutamine-excess cultures containing 4 mmol L(-1) glutamine
      in the feed medium. The specific consumption rates of nearly all amino acids
      decreased with increasing glutamine feed, indicating that, in their metabolic
      function, they may partially be replaced by glutamine. Both cell lines reacted
      similarly to differences in glutamine feeding in all aspects investigated, except
      for glucose metabolism, In SP2/0-Ag14 glutamine feed concentrations did not
      affect the specific glucose consumption, whereas in MN12 this parameter increased
      with increasing amounts of glutamine fed. This systematic study using controlled
      culture conditions together with a detailed analysis of culture data shows that,
      although cells may react similarly in many aspects, cell-line-specific
      characteristics may be encountered even with respect to fundamental physiological
      responses like the interaction of the glutamine and glucose metabolism.

PMID- 18634094
TI  - Papain catalyzed synthesis of glyceryl esters of N-protected amino acids and
      peptides for the use in trypsin catalyzed peptide synthesis.
AB  - Papain catalyzed synthesis of glyceryl esters of BOC(Z)-protected amino acids and
      peptides was performed at 40-50 degrees C in a 50 molar excess of glycerol.
      Equilibrium was achieved in 6-7 h. The maximal yield of esters (50-70%) was
      obtained at 10% of water and pH 3.2-3.4. A lower water concentration resulted in
      a sharp decrease of the ester yield. The synthesized glyceryl esters of neutral
      amino acids are good substrates for trypsin and can be used for peptide synthesis
      catalyzed for trypsin. Glycerol esters are also good substrates for other enzymes
      possessing esterase activity.

PMID- 18634095
TI  - Selective separation of amino acids with a charged inorganic nanofiltration
      membrane: effect of physicochemical parameters on selectivity.
AB  - A charged organic-inorganic nanofiltration (NF) membrane prototype was used to
      separate a mixture of nine amino acids (AA) on the basis of differential
      electrostatic interactions with the membrane because, for a given pH, some of
      them were positively charged, some were negative, and some were zwitterions.
      Effect of pH, amino acid concentration (C(r)), and added ionic strength ([NaCI])
      on the process selectivity was studied. A global statistical study revealed that
      pH was the dominant parameter regarding fractionation. C(r) and [NaCI] had a
      weaker effect, but the ratio C(r)/[NaCI] demonstrated a pronounced effect on
      system selectivity. Two split-ups of the mixture were obtained at pH 2 and at pH
      12, for a 1-g/L total AA concentration and a C(r)/[NaCI] ratio of 0.16. Under
      these conditions, the differences in transmissions between basic and acid AA were
      higher than 70%. Interpretation of the results according to the Donnan theory
      allows us to foresee the potentialities of charged nanofiltration membranes for
      the fractionation of a complex mixture, such as peptidic hydrolysate to streams
      containing peptides and amino acids having different isoelectric points. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 54: 291-302, 1997.

PMID- 18634096
TI  - Analysis of phase composition in aqueous two-phase systems using a two-column
      chromatographic method: Application to lactic acid production by extractive
      fermentation.
AB  - A new chromatographic system for the simultaneous analysis of polyethylene
      glycol, dextran, sugars, and low-molecular-weight fatty acids was developed. The
      system is based on a gel exclusion column which allows a first separation between
      high- and low-molecular-weight compounds, and a cationic exchange column used to
      further separate the low-molecular-weight compounds. Two applications of the
      system were demonstrated: (i) after optimizing eluent conditions the gel
      exclusion column was used to determine the influence of lactic acid, phosphate
      buffer, and lactic acid bacteria on the ethylene oxide propylene oxide-dextran
      T40 phase diagram by HPLC; (ii) the ion exchange column was coupled in series
      with the gel exclusion column and the concentration of polyethylene glycol,
      dextran, glucose, lactate, acetate, and formate was determined in samples from
      the fermentative production of lactic acid in a polyethylene glycol 8000-dextran
      T40 aqueous two-phase system. The fermentation was operated without pH control in
      a repeated extractive batch mode, where the cell-free top phase was replaced four
      times, whereas the cell-containing bottom phase was reused repeatedly. The yield
      was 1.1 mol of lactic acid formed per mole of glucose added and the productivity
      was 4.7 mM.h(-1). The polymeric composition of the fermentation system was
      monitored during the five repeated extractive batches, and it showed a
      progressive depletion in polyethylene glycol and a progressive enrichment in
      dextran. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 303-311, 1997.

PMID- 18634097
TI  - Bleach boosting and direct brightening by multiple xylanase treatments during
      peroxide bleaching of kraft pulps.
AB  - The effects of multiple xylanase treatments were assessed during the peroxide
      bleaching of three pulps: Douglas-fir (kraft); Western hemlock (oxygen
      delignified kraft); and trembling Aspen (kraft). The addition of a xylanase
      treatment stage, either before or after the peroxide bleaching stage(s), resulted
      in the enhanced brightening of all pulps. A higher brightness was achieved using
      two enzyme treatments, one before and one after the peroxide stage(s). Both
      bleach boosting and direct brightening seemed to contribute to the enhancement of
      the peroxide bleaching. Compared to xylanase prebleaching, xylanase posttreatment
      of peroxide bleached pulps solubilized less lignin and chromophores and made
      smaller amounts of these materials alkaline soluble. Nevertheless, the final
      brightness achieved by xylanase posttreatment was similar or superior to that
      achieved with xylanase prebleaching of the corresponding unbleached pulps. (c)
      1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 312-318, 1997.

PMID- 18634098
TI  - Microbially enhanced chemisorption of nickel into biologically synthesized
      hydrogen uranyl phosphate: a novel system for the removal and recovery of metals
      from aqueous solutions.
AB  - Ni(2+) was removed quantitatively from aqueous flows by columns loaded with
      polycrystalline hydrogen uranyl phosphate (HUP) bound to immobilized cells of
      Citrobacter sp. The columns functioned effectively in Ni uptake/regeneration
      cycles; five cycles were completed without significant decrease in the Ni
      removing capacity of the column. The influence of pH, temperature, and flow rate
      on the Ni-removing capacity of the columns was examined. The composition of the
      Ni/HUP cell-bound deposits was confirmed by X-ray diffraction analysis (XRD) and
      proton-induced X-ray emission (PIXE) spectroscopy following several consecutive
      metal challenges and is discussed in relation to the mechanism of Ni(2+) removal
      from solution via ion-exchange intercalation into the interlayer space of HUP. Ni
      was selectively recovered from the columns using citrate or tartrate. The
      regenerated columns functioned effectively in Ni removal throughout repeated Ni
      challenge and desorption cycles. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 54: 319-328, 1997.

PMID- 18634099
TI  - Enzyme entrapped inside the reversed micelle in the fabrication of a new urea
      sensor.
AB  - A new improvised urea sensor is described. The new sensor makes use of entrapment
      inside reversed micelles as a method for enzyme immobilization and glass
      electrode for the purpose of sensing. Urea content in clinical blood samples has
      been estimated using this new sensor. Agreement of the results thus obtained with
      those from clinical methods gives credence to the new sensor. (c) 1997 John Wiley
      & Sons, Inc. Biotechnol Bioeng 54: 329-332, 1997.

PMID- 18634100
TI  - Polymerization mechanism of polypeptide chain aggregation.
AB  - The misfolding of polypeptide chains and aggregation into the insoluble inclusion
      body state is a serious problem for biotechnology and biomedical research.
      Developing a rational strategy to control aggregation requires understanding the
      mechanism of polymerization. We investigated the in vitro aggregation of P22
      tailspike polypeptide chains by classical light scattering, nondenaturing gel
      electrophoresis, two-dimensional polyacrylamide gel electrophoresis (PAGE), and
      computer simulations. The aggregation of polypeptide chains during refolding
      occurred by multimeric polymerization, in which two multimers of any size could
      associate to form a larger aggregate and did not require a sequential addition of
      monomeric subunits. The cluster-cluster polymerization mechanism of aggregation
      is an important determinant in the kinetic competition between productive folding
      and inclusion body formation. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng
      54: 333-343, 1997.

PMID- 18634101
TI  - Assessment of interference in biosorption of a heavy metal.
AB  - Nonliving biomass of Sargassum, a brown marine alga, is capable of binding more
      than 10% of its dry weight in toxic cadmium ions. Although ubiquitous iron
      interferes with Cd uptake, only approximately 4.5% of it is sequestered (biomass
      dry weight). Biosorption of both metals at ph 4.5 could be described by Langmuir
      type isotherms with b, the affinity-related coefficient (Cd: b = 0.015; Fe: b =
      0.027). The interference of Fe with Cd uptake, and vice versa, was assessed by
      deriving three-dimensional equilibrium two-metal sorption isotherm surfaces,
      smoothed and "cut" to reveal the inhibition effect of Fe on biosorption of Cd: at
      the equilibrium concentration Cf[Cd] = 1.5 mM, the presence of Fe at 1.5 mM
      equilibrium concentration suppressed the Cd uptake to only 76% of the original
      value. For 50% Cd uptake reduction, a very high equilibrium Fe presence of 4.5 mM
      was required. The Cd presence affected the uptake of Fe very strongly. To obtain
      equal values of uptake for each metal in the biosorbent, the ratio of equilibrium
      concentrations of 0.42 Cd to 1 Fe is necessary in the liquid phase. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 54: 344-350, 1997.

PMID- 18634102
TI  - Enzymatic synthesis of sorbitan esters using a low-boiling-point azeotrope as a
      reaction solvent.
AB  - Sorbitan esters were prepared by controlled dehydration of sorbitol followed by
      lipase-catalyzed esterification of the resulting "sorbitan." The reaction was
      carried out in azeotropic mixtures of tert-butanol/n-hexane. A partial phase
      diagram to determine the temperature required for the distillation of the
      azeotrope at a given ratio of the solvents was constructed. The effect of varying
      concentrations of the two solvents on the rate of esterification and the
      monoester/diester ratio of the final product was investigated in detail. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 54: 351-356, 1997.

PMID- 18634103
TI  - Effect of growth factors and antigen on hybridoma cell culture dynamics.
AB  - The cell growth and monoclonal antibody production kinetics of hybridoma cell
      cultures continuously exposed to growth factors and the cognate antigen were
      investigated. The growth factors were the epidermal growth factor, fibroblast
      growth factor, and interleukin-2, whereas the antigen was the trinitrophenyl
      group conjugated to a carrier protein. The cultures were carried out in a protein
      free medium in batch operation. During the entire cultivation period there was
      continuously available free, antibody-unbound antigen to interact with the cells.
      The produced antibody was measured with an ELISA after it was released from the
      antigen-protein conjugate by competitive elution with non-protein-conjugated
      antigen. Cultures with growth factors and without antigen increased the total
      antibody produced by up to 30%, whereas cell growth remained unaffacted. Soluble
      antigen-protein conjugates had no effect on the hybridoma cultures. In contrast,
      immobilized antigen-protein on sepharose beads in cultures with growth factors
      induced significant changes. Total antibody produced was higher by up to 40%.
      More importantly, the specific antibody production shifted from a growth-phase
      independent to a growth-phase-dependent profile, with approximately twice as much
      specific antibody production during the late growth-early stationary phase
      relative to constant specific antibody production in the antigen-free, factor
      free culture. The culture changes induced by the presence of immobilized antigen
      and growth factors were reversed when the antigen and the growth factors were
      removed from the cells' environment. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 54: 357-364, 1997.

PMID- 18634104
TI  - The aggregated form of an AAMP derived peptide behaves as a heparin sensitive
      cell binding agent.
AB  - A peptide termed P189, derived from the sequence of a newly discovered protein,
      AAMP (angio-associated migratory cell protein), contains a motif that is
      predicted to a bind heparin. It occurs near the amino terminal end of AAMP.
      Previous studies have shown that in its solubilized form P189 (RRLRRMESESES)
      binds heparin and melanoma cells. The peptide is bipolar in that it contains
      positive charges at its amino end and negative charges at its carboxyl end. It
      forms strongly aggregated particles that require exposure to 50% DMSO and 100
      degrees C for solubilization to occur. Now heparin and cell binding (heparin
      sensitive) are also demonstrated for the peptide in its particular form. Cell
      binding/clustering to the peptide particles is strong and resists exposure to
      various reagents (sugars and inhibitors of glycolysis and protein synthesis)
      except heparin. Tumor cell migration is partially inhibited by the presence of
      the peptide. On electron photomicrographs the peptide is seen in close apposition
      to cell membranes. Heparin sensitivity of the cell binding indicates that cell
      surface glycosaminoglycans are involved. The aggregated peptide binds heparin in
      a saturable manner with a dissociation constant, K(d), of 306 pmol. Cell
      binding/clustering studies using peptide variants of P189, which have
      substitutions in either the charged and/or nonpolar residues, show that the
      specific sequence of P189 optimizes heparin-sensitive cell aggregation. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 54: 365-372, 1997.

PMID- 18634105
TI  - IMAC: nonlinear elution chromatography of proteins.
AB  - Nonlinear elution chromatography of proteins employing the traditional mobile
      phase modulators in IMAC has been studied using the metal affinity interaction
      model (MAIC) in conjunction with the chromatographic mass transport equations.
      Results indicate that when the feed is loaded under conditions that foster
      constant pattern formation, isocratic elution leads to Langmuirian profiles at
      low mobile phase modulator (MPM) concentrations and a double-plateau profile at
      high concentrations. A non-self-sharpening protein front during loading, on the
      other hand, can lead to three plateau profiles or peak splitting and ghost peak
      formation. Experimental and simulation results on protein separations employing
      high-affinity modulators suggest that elution with loading in the absence of
      modulators leads to considerably higher throughputs and protein concentrations
      due to the displacement effects of the modulator as it migrates through the
      protein zones. Also, for certain separation problems, the operating conditions
      can be chosen such that the complex modulator system peaks manifest themselves as
      spacer displacer; affecting a sharper rear of the earlier eluting protein and an
      efficient separation. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54:373
      390, 1997.

PMID- 18634106
TI  - Fed-batch xylitol production with two recombinant Saccharomyces cerevisiae
      strains expressing XYL1 at different levels, using glucose as a cosubstrate: a
      comparison of production parameters and strain stability.
AB  - Xylitol production with two recombinant Sacharomyces cerevisiae strains
      expressing the XYL1 gene, coding for xylose reductase (XR), at different levels,
      the 'low XR strain' at 0.51 U/mg and the 'high XR strain' at 10.8 U/mg, was
      compared in batch and fed-batch culture. Xylose was not consumed in the presence
      of high glucose concentrations, because both sugars are transported by the
      glucose transport system, which has a higher affinity for glucose than for
      xylose. When glucose was fed gradually to the culture, high concentrations were
      avoided, and xylose was converted to xylitol with a specific productivity of 0.10
      g g(-1) h(-1) attained with the low XR strain and 0.19 g g(-1) h(-1) with the
      high XR strain, indicating that factors other than the XR-activity control the
      rate of xylose conversion.The overproduction of XR put a substantial protein
      burden on the high XR strain, contributing to a 50% decrease in specific growth
      rate and reduced biomass yield compared with the low XR strain. Despite the use
      of selective medium, the stability of the high XR strain was poor in long fed
      batch and chemostat cultures, whereas the low XR strain was stable. The high XR
      strain lost its XR activity almost completely in some fed-batch cultures and in
      chemostat culture. In chemostat cultivation, part of the population lost the
      plasmid harboring the XR gene. This was due to the fact that leucine was released
      into the broth from plasmid containing cells, which enabled some cells to grow
      without the plasmid containing the LEU2 auxotrophic complementation selection
      marker. Furthermore, isolation and analysis of plasmids from a population that
      had lost its XR activity, showed that in addition to the original plasmid, a
      rearranged form of the plasmid, retaining the selection marker but not the
      expression of active XR, was present. However, these observations could only
      partly explain the decrease in XR activity. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 54: 391-399, 1997.

PMID- 18634108
TI  - Levoatrial cardinal vein in mitral atresia and closed foramen ovale: prenatal
      diagnosis and perinatal management.
AB  - A levoatrial cardinal vein is a rare cardiovascular anomaly that may be present
      in malformed hearts with severe left heart obstruction and restrictive
      interatrial communication. We report the prenatal diagnosis at 23 weeks of a
      fetus with mitral atresia, double-outlet right ventricle, premature closure of
      the foramen ovale and a levoatrial cardinal vein draining into the innominate
      vein. In a prior examination performed elsewhere the levoatrial cardinal vein had
      been interpreted as an aortic arch perfused retrogradely, and hypoplastic left
      heart syndrome with aortic atresia had been diagnosed. Prenatal management,
      induction at 38 weeks and postnatal examinations and treatment are reported. To
      the best of our knowledge, this is the first reported prenatal diagnosis of this
      embryological vessel, presenting a potential pitfall for prenatal
      echocardiography.

PMID- 18634109
TI  - Semi-automatic segmentation of fetal cardiac cavities: progress towards an
      automated fetal echocardiogram.
AB  - OBJECTIVE: To develop a novel application of a tool for semi-automatic volume
      segmentation and adapt it for analysis of fetal cardiac cavities and vessels from
      heart volume datasets. METHODS: We studied retrospectively virtual cardiac volume
      cycles obtained with spatiotemporal image correlation (STIC) from six fetuses
      with postnatally confirmed diagnoses: four with normal hearts between 19 and 29
      completed gestational weeks, one with d-transposition of the great arteries and
      one with hypoplastic left heart syndrome. The volumes were analyzed offline using
      a commercially available segmentation algorithm designed for ovarian
      folliculometry. Using this software, individual 'cavities' in a static volume are
      selected and assigned individual colors in cross-sections and in 3D-rendered
      views, and their dimensions (diameters and volumes) can be calculated. RESULTS:
      Individual segments of fetal cardiac cavities could be separated, adjacent
      segments merged and the resulting electronic casts studied in their spatial
      context. Volume measurements could also be performed. Exemplary images and
      interactive videoclips showing the segmented digital casts were generated.
      CONCLUSION: The approach presented here is an important step towards an automated
      fetal volume echocardiogram. It has the potential both to help in obtaining a
      correct structural diagnosis, and to generate exemplary visual displays of
      cardiac anatomy in normal and structurally abnormal cases for consultation and
      teaching.

PMID- 18634110
TI  - Investigation of norflurazon pesticide photodegradation using plasma desorption
      time-of-flight mass spectrometry analysis.
AB  - We have previously demonstrated that PD-TOFMS (plasma desorption time-of-flight
      mass spectrometry) analysis is a powerful technique for the in situ analysis of
      pesticides deposited or adsorbed on solid materials. With the aim of producing
      reproducible data on the modification of a pesticide under controlled
      photodegradation conditions, we have now undertaken a study where both the
      substrate and the pesticide are well characterized. This is the case for
      norflurazon deposited onto an aluminium substrate, in particular regarding the
      reproducibility of preparation of the samples and the change with time of their
      chemical composition. Degradation parameters have been derived from the variation
      in yield of ions representative of the molecule and of its breakdown products
      and, particularly, from the time required for 50% dissipation of their initial
      concentration (DT50). DT50 values ranging between 1 and 10 h have been found. An
      interpretation of the degradation process is proposed from the decay of other
      ions. As expected, the degradation is faster when the UV sunlight is unfiltered
      (a factor of 3.8 for the molecule, and around 5 for the breakdown products).

PMID- 18634111
TI  - Hydrogen/deuterium exchange on protein solutions containing nucleic acids:
      utility of protamine sulfate.
AB  - Obtaining global hydrogen/deuterium (H/D) exchange data on proteins is an
      important first step in amide proton exchange experiments. Important information
      such as the mode of exchange, the cooperativity of folding/unfolding reactions,
      and the effects of ligand binding can be readily obtained in global exchange
      experiments. Many interesting biological systems are complexes containing both
      proteins and nucleic acids. The low pH conditions required to quench H/D exchange
      reactions result in the formation of stable protein/nucleic acid precipitates
      which interfere with the liquid chromatography step of the experiment and
      preclude obtaining mass spectrometric data. In this work we show that the
      precipitation of proteins and nucleic acids is electrostatic in nature and can be
      prevented by high ionic strength and by removing nucleic acids by protamine
      sulfate. Using protamine sulfate in quenching solution, we were able to obtain
      global H/D data with protein samples containing large amounts of DNA or RNA.

PMID- 18634112
TI  - Characterization of spirostanol saponins in Solanum torvum by high-performance
      liquid chromatography/evaporative light scattering detector/electrospray
      ionization with multi-stage tandem mass spectrometry.
AB  - High-performance liquid chromatography with an evaporative light scattering
      detector and electrospray ionization multistage tandem mass spectrometry
      (HPLC/ELSD/ESI-MS(n)) was used to identify spirostanol saponins in a saponin
      extract of Solanum torvum. The fragmentation behavior of saponins was studied
      using ESI-MS(1-3) in positive ion mode. The MS(n) spectra of the [M+H](+) ions
      provide structural information including aglycone type and the nature and
      sequence of sugars. The use of ELSD allowed the profiling of the nonchromophore
      containing saponins in this plant. The MS analysis established in this study with
      known saponins was successfully applied to tentatively identify two new
      siprostanol glycosides, neosolaspigenin 6-O-beta-D-quinovopyranoside and
      solagenin 6-O-[beta-D-xylopyranosyl-(1 --> 3)-O-beta-D-quinovopyranoside].

PMID- 18634113
TI  - Detrusor wall thickness as a test for detrusor overactivity in women.
AB  - OBJECTIVE: The measurement of detrusor wall thickness has been used as a
      screening test for detrusor overactivity and bladder outlet obstruction in men
      and women. The aim of this study was to determine, using receiver-operating
      characteristics (ROC) analysis, the diagnostic value of detrusor wall thickness
      in predicting detrusor overactivity in women. METHODS: The records of 686 women
      who attended a tertiary urodynamics service from November 2002 to January 2006
      were retrospectively reviewed. The patients had undergone an interview, clinical
      examination, multichannel urodynamic studies and translabial ultrasound
      examination. Detrusor wall thickness measurements were taken at the bladder dome,
      after bladder emptying. ROC analysis was used to identify the optimal cut-off of
      detrusor wall thickness in predicting detrusor overactivity. RESULTS: Average
      detrusor wall thickness in the detrusor overactivity group was 4.7 +/- 1.9 mm
      (mean +/- SD), compared to 4.1 +/- 1.6 mm in the non-detrusor overactivity group
      (P < 0.001). Using a cut-off of detrusor wall thickness of 5.0 mm gave a
      sensitivity of 37% and a specificity of 79% for diagnosing detrusor overactivity.
      The ROC analysis revealed an area under the curve (AUC) of 0.606 (95% CI, 0.56
      0.65). CONCLUSIONS: There is a statistically significant association between
      detrusor wall thickness and detrusor overactivity (P < 0.001). However, ROC
      analysis demonstrated that detrusor wall thickness as measured by translabial
      ultrasound is of little use as a diagnostic test for detrusor overactivity,
      giving an AUC of only 0.606. Measurement of detrusor wall thickness should
      therefore not be used as a diagnostic parameter for detrusor overactivity in
      women.

PMID- 18634114
TI  - In utero therapy for fetal thoracic abnormalities.
AB  - Fetal thoracic lung anomalies are rare. The specific diagnosis can be made by
      utilizing ultrasound, magnetic resonance imaging (MRI), and Doppler studies.
      Perinatal surveillance is required for large lesions and mediastinal shift
      regardless of the pathological diagnosis. These can cause physiological changes
      in the cardiovascular system with resulting hydrops. In utero therapies are
      variable but with no large randomized trials to compare risks and benefits. In
      most cases of fetal lung lesions, continued observation with postnatal therapy is
      the outcome. When fetal hydrops is present or impending, in utero fetal therapy
      is required to try to reverse that pathological course associated with fetal or
      neonatal death. Maternal morbidity is increased with the development of MIRROR
      syndrome following the presence of long-standing fetal hydrops and possible
      surgical procedures.

PMID- 18634115
TI  - Cystic lung lesions - prenatal diagnosis and management.
AB  - With increasing use of fetal ultrasound comes an increase in the detection of
      clinically silent 'abnormalities' which pose diagnostic and management dilemmas
      for perinatologists and paediatricians. Congenital thoracic malformations (CTMs)
      (excluding congenital diaphragmatic hernia) are one such example, where a few
      cases are symptomatic in early life and management options are clear, but the
      majority are clinically asymptomatic, giving rise to difficulties in defining
      postnatal management of the well child with a sonographic or radiological lesion.
      Here, we will outline the prenatal presentation and natural history of CTMs that
      are not congenital diaphragmatic herniae and briefly discuss the approach to
      postnatal management, which is covered in more detail in the review by Laje and
      Liechty in this issue.

PMID- 18634116
TI  - Prenatal diagnosis, prediction of outcome and in utero therapy of isolated
      congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) can be associated with genetic or
      structural anomalies with poor prognosis. In isolated cases, survival is
      dependent on the degree of lung hypoplasia and liver position. Cases should be
      referred in utero to tertiary care centers familiar with this condition both for
      prediction of outcome as well as timed delivery. The best validated prognostic
      indicator is the lung area to head circumference ratio. Ultrasound is used to
      measure the lung area of the index case, which is then expressed as a proportion
      of what is expected normally (observed/expected LHR). When O/E LHR is < 25%
      survival chances are < 15%. Prenatal intervention, aiming to stimulate lung
      growth, can be achieved by temporary fetal endoscopic tracheal occlusion (FETO).
      A balloon is percutaneously inserted into the trachea at 26-28 weeks, and
      reversal of occlusion is planned at 34 weeks. Growing experience has demonstrated
      the feasibility and safety of the technique with a survival rate of about 50%.
      The lung response to, and outcome after FETO, is dependent on pre-existing lung
      size as well gestational age at birth. Early data show that FETO does not
      increase morbidity in survivors, when compared to historical controls. Several
      trials are currently under design.

PMID- 18634117
TI  - Sonographic development of the normal foetal thorax and abdomen across gestation.
AB  - In the following review, the development of the thorax and abdomen, as described
      by embryologists and anatomists in modern embryological text books, is compared
      with sonoanatomic descriptions from 2D and 3D ultrasound studies, week by week in
      the first trimester. The anatomic descriptions are limited to details that are of
      interest for the understanding of ultrasound examinations. For the second and
      third trimester, the description of the sonographic development of the thorax and
      abdomen is divided into thoracic skeleton, diaphragm, lungs, oesophagus, stomach,
      liver, spleen, bowel and gall bladder. The review is restricted to the normal
      development, appearance and biometric assessment of these organs; and discusses
      topical literature.

PMID- 18634118
TI  - Anomalies of the fetal thorax and abdomen: diagnosis, management and outcome.

PMID- 18634119
TI  - Prenatal and postnatal management of omphalocele.
AB  - Omphalocele is one of the most common abdominal wall defects seen in the prenatal
      period. Once this diagnosis is confirmed, it is important to check the fetal
      karyotype and thoroughly assess the fetus for other malformations. Prenatal
      management involves serial assessment of fetal growth and prenatal testing to
      ensure fetal well-being. Closure of the abdominal wall and replacement of organs
      into the abdominal cavity can be done directly if the omphalocele is small or in
      a staged manner if the omphalocele is large. Successful outcomes for these
      neonates can be optimized with a multidisciplinary team approach to prenatal and
      postnatal management.

PMID- 18634120
TI  - Syndromic associations with congenital anomalies of the fetal thorax and abdomen.
AB  - Anomalies of the thorax and abdomen can be found in a number of genetic
      syndromes. Whilst it may not be possible to make a definitive diagnosis before
      birth, knowledge of the potential associations can be useful for the prenatal
      diagnostician when examining the fetus and counselling the parents. In this
      article, we describe conditions where other features may be detectable using
      prenatal ultrasound. We describe the features, potential diagnostic aids and
      prognosis. The tables list other potential features that may be identified. The
      range of conditions that can occur emphasises the value of genetic input in the
      management of a fetus with an apparently normal karyotype and multiple anomalies,
      the need to save material for future molecular analysis and the requirement of a
      detailed examination after delivery. These are needed in order to make accurate
      diagnoses and advise parents with regard to recurrence risks and the potential
      for prenatal diagnosis in future pregnancies.

PMID- 18634121
TI  - Have newer cardiovascular drugs reduced hospitalization? Evidence from
      longitudinal country-level data on 20 OECD countries, 1995-2003.
AB  - This study examines the effect of changes in the vintage distribution of
      cardiovascular system drugs on hospitalization and mortality due to
      cardiovascular disease using longitudinal country-level data. The vintage of a
      drug is the first year in which it was marketed anywhere in the world. We use
      annual data on the utilization of over 1100 cardiovascular drugs (active
      ingredients) in 20 OECD countries during the period 1995-2003. Countries with
      larger increases in the share of cardiovascular drug doses that contained post
      1995 ingredients had smaller increases in the cardiovascular disease hospital
      discharge rate, controlling for the quantity of cardiovascular medications
      consumed per person, the use of other medical innovations (computed tomography
      scanners and magnetic resonance imaging units), potential risk factors (average
      consumption of calories, tobacco, and alcohol), and demographic variables
      (population size and age structure, income, and educational attainment). The
      estimates also indicate that the use of newer cardiovascular drugs has reduced
      the average length of stay and the age-adjusted cardiovascular mortality rate,
      but not the number of potential years of life lost due to cardiovascular disease
      before age 70 per 100,000 population. The estimates indicate that if drug vintage
      had not increased during 1995-2004, hospitalization and mortality would have been
      higher in 2004. We estimate that per capita expenditure on cardiovascular
      hospital stays would have been 70% ($89) higher in 2004 had drug vintage not
      increased during 1995-2004. Per capita expenditure on cardiovascular drugs would
      have been lower in 2004 had drug vintage not increased during 1995-2004. However,
      our estimate of the increase in expenditure on cardiovascular hospital stays is
      about 3.7 times as large as our estimate of the reduction in per capita
      expenditure for cardiovascular drugs that would have occurred ($24).

PMID- 18634123
TI  - Doping control analysis of tricyclic tetrahydroquinoline-derived selective
      androgen receptor modulators using liquid chromatography/electrospray ionization
      tandem mass spectrometry.
AB  - Selective androgen receptor modulators represent an emerging class of
      therapeutics to counteract various diseases such as osteoporosis and muscle
      wasting. Numerous drug candidates have been developed and investigated including
      a group that comprises a tricyclic tetrahydroquinoline nucleus such as 2-methyl-2
      (8-nitro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]chinolin-4-yl)propan-1-ol. Due to
      their novelty and medicinal purpose, these compounds also possess great potential
      for misuse in sports, and studies on the mass spectrometric behavior of three
      synthesized model substances and drug candidates were conducted to provide
      information on typical dissociation pathways following electrospray ionization
      and collision-induced dissociation. Product ion mass spectra derived from
      protonated molecules were studied using high resolution/high accuracy orbitrap
      mass spectrometry, and characteristic fragmentation routes and product ions were
      elucidated. Major and general findings include the elimination of a hydroxyl
      radical from [M+H](+), the elimination of the 2-substituted side chain, and the
      gas-phase rearrangement of the investigated tricyclic tetrahydroquinolines to 6
      nitroquinoline yielding a common product ion at m/z 175. Knowledge of these
      dissociation pathways supports the identification of related substances as well
      as metabolic products, which is of utmost importance to drug testing
      laboratories. The compounds were implemented into existing screening procedures,
      and detection limits (0.2-0.6 ng/mL), recoveries (92-97%), and intraday and
      interday precision (<22%) were evaluated.

PMID- 18634124
TI  - Measurement of sugars using the laser spray technique with a gold capillary.
AB  - A gold (Au) capillary has higher thermal conductivity than a stainless steel
      capillary and can withstand capillary over-heating induced by high CO(2) laser
      irradiation (over 2.5 W) better than a stainless steel capillary. For this study,
      a laser spray using an Au capillary was applied for the detection of sugars. The
      signal of cationized compounds [M+Na](+) can be detected with higher sensitivity
      than with conventional laser sprays using high laser power (over 2.7 W). Using
      3.5 W of laser power, the signal intensity is 15 times higher than the maximum
      value with stainless steel (2.3 W) in a 10(-5) M maltose aqueous solution. It is
      considered that almost all the water molecules evaporate by laser irradiation,
      which is impossible to achieve using a stainless steel capillary.

PMID- 18634122
TI  - Quantification of key red blood cell folates from subjects with defined MTHFR
      677C>T genotypes using stable isotope dilution liquid chromatography/mass
      spectrometry.
AB  - Red blood cell (RBC) folate levels are established at the time of erythropoiesis
      and therefore provide a surrogate biomarker for the average folate status of an
      individual over the preceding four months. Folates are present as
      folylpolyglutamates, highly polar molecules that cannot be secreted from the
      RBCs, and must be converted into their monoglutamate forms prior to analysis.
      This was accomplished using an individual's plasma pteroylpolyglutamate hydrolase
      by lysing the RBCs in whole blood at pH 5 in the presence of ascorbic acid.
      Quantitative conversion of formylated tetrahydrofolate derivatives into the
      stable 5,10-methenyltetrahydrofolate (5,10-MTHF) form was conducted at pH 1.5 in
      the presence of [(13)C(5)]-5-formyltetrahydrofolate. The resulting [(13)C(5)]
      5,10-MTHF was then used as an internal standard for the formylated forms of
      tetrahydrofolate that had been converted into 5,10-MTHF as well any 5,10-MTHF
      that had been present in the original sample. A stable isotope dilution liquid
      chromatography-multiple reaction monitoring/mass spectrometry method was
      validated and then used for the accurate and precise quantification of RBC folic
      acid, 5-methyltetrahydrofolate (5-MTHF), tetrahydrofolate (THF), and 5,10-MTHF.
      The method was sensitive and robust and was used to assess the relationship
      between different methylenetetrahydrofolate reductase (MTHFR) 677C>T genotypes
      and RBC folate phenotypes. Four distinct RBC folate phenotypes could be
      identified. These were classified according to the relative amounts of individual
      RBC folates as type I (5-MTHF >95%; THF <5%; 5,10-MTHF <5%), type II (5-MTHF
      <95%; THF 5% to 20%; 5,10-MTHF <5%), type III (5-MTHF >55%; THF >20%; 5,10-MTHF
      >5%), and type IV (5-MTHF <55%; THF >20%; 5,10-MTHF >5%).

PMID- 18634125
TI  - Metabonomics investigation of human urine after ingestion of green tea with gas
      chromatography/mass spectrometry, liquid chromatography/mass spectrometry and
      (1)H NMR spectroscopy.
AB  - A method using gas chromatography/mass spectrometry (GC/MS), liquid
      chromatography/mass spectrometry (LC/MS) and (1)H NMR with pattern recognition
      tools such as principle components analysis (PCA) was used to study the human
      urinary metabolic profiles after the intake of green tea. From the normalized
      peak areas obtained from GC/MS and LC/MS and peak heights from (1)H NMR,
      statistical analyses were used in the identification of potential biomarkers.
      Metabolic profiling by GC/MS provided a different set of quantitative signatures
      of metabolites that can be used to characterize the molecular changes in human
      urine samples. A comparison of normalized metabonomics data for selected
      metabolites in human urine samples in the presence of potential overlapping peaks
      after tea ingestion from LC/MS and (1)H NMR showed the reliability of the current
      approach and method of normalization. The close agreements of LC/MS with (1)H NMR
      data showed that the effects of ion suppression in LC/MS for early eluting
      metabolites were not significant. Concurrently, the specificity of detecting the
      stated metabolites by (1)H NMR and LC/MS was demonstrated. Our data showed that a
      number of metabolites involved in glucose metabolism, citric acid cycle and amino
      acid metabolism were affected immediately after the intake of green tea. The
      proposed approach provided a more comprehensive picture of the metabolic changes
      after intake of green tea in human urine. The multiple analytical approach
      together with pattern recognition tools is a useful platform to study metabolic
      profiles after ingestion of botanicals and medicinal plants.

PMID- 18634126
TI  - Structural characterization and identification of ecdysteroids from Sida
      rhombifolia L. in positive electrospray ionization by tandem mass spectrometry.
AB  - Seven ecdysteroids isolated from Sida rhombifolia L. were studied by electrospray
      ionization multi-stage tandem mass spectrometry (ESI-MS(n)) in the positive ion
      mode using an ion trap analyzer and high-performance liquid chromatography
      coupled with a diode-array detector (HPLC/DAD). The HPLC experiments were
      performed by means of a reversed-phase C(18) column and a binary mobile phase
      system consisting of water (containing 0.05% formic acid) and acetonitrile
      (containing 0.05% formic acid) under gradient elution conditions. According to
      mass spectral features and the substitution at C-2, C-20, C-24 and C-25,
      ecdysteroids in S. rhombifolia were classified into three sub-groups. Structural
      identification of these three sub-groups of ecdysteroids was established by
      LC/multi-stage ion trap mass spectrometry on-line or off-line. The fragmentation
      patterns of ecdysteroids yielded ions of successive loss of 1-4 water molecules.
      Furthermore, ions corresponding to the complete loss of the side chain at C-17
      will help to identify the sub-groups of ecdysteroids in addition to containing a
      hydroxyl moiety at one of the above-mentioned positions. Based on the HPLC
      retention behavior, the diagnostic UV spectra and the molecular structural
      information provided by ESI-MS(n) spectra, a total of nine naturally occurring
      ecdysteroids were identified, of these two are identified for the first time in
      S. rhombifolia.

PMID- 18634128
TI  - Do microfinance programs help families insure consumption against illness?
AB  - Families in developing countries face enormous financial risks from major illness
      both in terms of the cost of medical care and the loss in income associated with
      reduced labor supply and productivity. We test whether access to microfinancial
      savings and lending institutions helps Indonesian families smooth consumption
      after declines in adult health. In general, results support the importance of
      these institutions in helping families to self-insure consumption against health
      shocks.

PMID- 18634129
TI  - Prenatal ultrasonographic diagnosis of persistent hyperplastic primary vitreous.
AB  - Persistent hyperplastic primary vitreous (PHPV) is a rare developmental
      malformation of the eye characterized by the presence of a vascular membrane
      located behind the lens. We report, for the first time in the literature, the
      identification on ultrasound examination of bilateral cataract and thickened
      hyaloid artery-lens junction, leading to a diagnosis of bilateral PHPV, in a
      fetus at 23 weeks' gestation. Histological examination at postmortem confirmed
      the prenatal diagnosis of bilateral PHPV and cataract. A thorough ultrasound
      examination of the fetal eye in cases with cataract is recommended.

PMID- 18634130
TI  - Progression of Doppler abnormalities in intrauterine growth restriction.
AB  - OBJECTIVE: To identify the sequence of progression of arterial and venous Doppler
      abnormalities from the onset of placental insufficiency in intrauterine growth
      restriction (IUGR). METHODS: Prospective observational study of singletons with
      IUGR (abdominal circumference < 5(th) percentile) who underwent serial
      standardized umbilical artery (UA), middle cerebral artery (MCA), ductus venosus
      (DV) and umbilical vein (UV) Doppler surveillance. Time intervals between
      progressive Doppler abnormalities and patterns of deterioration were related to
      UA Doppler status and gestational age. RESULTS: Six hundred and sixty-eight
      longitudinal examinations were performed in 104 fetuses, identifying three
      patterns of progression: (1) Mild placental dysfunction (n = 34) that remained
      confined to the UA/MCA. The UA became abnormal at a median of 32 weeks' gestation
      but the pulsatility index never exceeded 3 SD above normal. Progression took a
      median of 33 days, requiring delivery at a median of 35 weeks. (2) Progressive
      placental dysfunction (n = 49). Initially normal UA Doppler PI at 29 weeks'
      gestation increased beyond 3 SD, progressing to abnormal MCA, absent/reversed UA
      diastolic flow, abnormal DV, UV pulsations in 9-day intervals requiring delivery
      by 33 weeks. (3) Severe early-onset placental dysfunction (n = 21). Markedly
      elevated UA PI established by 27 weeks' gestation was associated with rapid (7
      day intervals) progression to abnormal venous Doppler with median delivery at
      30.6 weeks. Gestational age at onset, time to delivery and progression intervals
      were different between patterns (all P < 0.05). CONCLUSION: The characteristics
      of cardiovascular manifestations in IUGR are determined by the gestational age at
      onset and the severity of placental disease. Recognition of these factors is
      critical for planning fetal surveillance in IUGR.

PMID- 18634131
TI  - Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in
      the prediction of pre-eclampsia.
AB  - OBJECTIVE: To evaluate the performance of screening for pre-eclampsia by uterine
      artery pulsatility index (PI) at 11 + 0 to 13 + 6 weeks' gestation and the change
      in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks.
      METHODS: In 3107 singleton pregnancies attending for routine care at 11 + 0 to 13
      + 6 and 21 + 0 to 24 + 6 weeks' gestation we recorded maternal characteristics
      and medical and obstetric history, and measured uterine artery PI. The
      distributions of uterine artery PI were made Gaussian after logarithmic
      transformation and the log of the ratio of uterine artery PI at 21 + 0 to 24 + 6
      weeks to that at 11 + 0 to 13 + 6 weeks was calculated. Multiple regression
      analysis was used to determine which of the maternal variables and Doppler
      findings were significant predictors of early and late pre-eclampsia. The
      performance of screening was described by receiver-operating characteristics
      curves. RESULTS: Pre-eclampsia developed in 93 (3.0%) pregnancies, including 22
      (0.7%) in which delivery was before 34 weeks (early pre-eclampsia) and 71 (2.3%)
      with delivery at 34 weeks or more (late pre-eclampsia). Seventy-three (2.3%)
      women developed gestational hypertension, 346 (11.1%) delivered small-for
      gestational-age (SGA) babies with no hypertensive disorders and 2595 (83.5%) were
      unaffected by pre-eclampsia, gestational hypertension or SGA. Multiple regression
      analysis demonstrated that maternal variables, uterine artery PI at 11 + 0 to 13
      + 6 weeks and the change in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0
      to 24 + 6 weeks' gestation provided significant independent contributions to the
      prediction of pre-eclampsia. For a false positive rate of 5% the predicted
      detection rates of early and late pre-eclampsia were 90.9 and 31.0%,
      respectively. The same performance of screening was achieved by reserving second
      trimester testing for only the 20% of women at the highest risk after first
      trimester screening. CONCLUSION: The decrease in uterine artery PI between 11 + 0
      to 13 + 6 and 21 + 0 to 24 + 6 weeks is steeper in pregnancies with a normal
      outcome than in those developing pre-eclampsia. Effective screening for pre
      eclampsia can be achieved by the Doppler measurement of uterine artery PI at 11 +
      0 to 13 + 6 weeks and the change in PI between 11 + 0 to 13 + 6 and 21 + 0 to 24
      + 6 weeks.

PMID- 18634132
TI  - Heart stroke volume and cardiac output by four-dimensional ultrasound in normal
      fetuses.
AB  - OBJECTIVE: To establish reference intervals for fetal heart stroke volume and
      cardiac output with gestation. METHODS: Fetal heart ventricular volumes were
      measured using the four-dimensional (4D) spatiotemporal imaging correlation
      (STIC) ultrasound technique in 140 normal singleton pregnancies at 12-34 weeks'
      gestation. The Virtual Organ Computer-aided AnaLysis (VOCAL) technique was used
      to obtain a sequence of six sections of each ventricular volume in systole and
      diastole. Each volume was obtained after a 30 degrees rotation from the previous
      one around a fixed axis extending from the apex of the heart to the point that
      divides symmetrically each atrioventricular valve. The contour of each ventricle
      was drawn manually and the 4D volumes of the left and right ventricle in systole
      and diastole were estimated. The stroke volume for each ventricle was then
      calculated by subtracting the one in systole from the one in diastole and the
      cardiac output was calculated by multiplying the stroke volume by the fetal heart
      rate. In 50 cases the stroke volumes were measured by the same sonographer twice
      and the intraobserver agreement of measurements was calculated. RESULTS: The left
      and right stroke volume and cardiac output increased exponentially with
      gestation, from respective mean values of 0.02 mL, 0.01 mL, 2.39 mL/min and 1.80
      mL/min at 12 weeks to 0.30 mL, 0.32 mL, 43.46 mL/min and 46.72 mL/min at 20
      weeks, and 2.07 mL, 2.67 mL, 284.71 mL/min and 365.99 mL/min at 34 weeks. The
      ratio of right to left stroke volume increased significantly with gestation from
      about 0.97 at 12 weeks to 1.13 at 34 weeks. In the Bland-Altman test, the mean
      percentage difference and 95% limits of intraobserver agreement for left stroke
      volume and right stroke volume were - 2.1 (-18.4, 14.2)% and - 0.8 (-16.4,
      18.0)%, respectively. CONCLUSIONS: In normal fetuses the stroke volume and
      cardiac output increase between 12 and 34 weeks' gestation. The extent to which,
      in pathological pregnancies, possible deviations in these measurements from
      normal prove to be useful in the prediction of outcome remains to be determined.

PMID- 18634133
TI  - Production of monoclonal antibodies by tobacco hairy roots.
AB  - Hairy roots of tobacco (Nicotiana tabacum) were used to produce full-length
      murine lgG(1) monoclonal antibody. The presence of heavy (gamma) and light
      (kappa) chains and fully assembled antibody was verified by Western blot analysis
      of root extracts. Antibody levels in the biomass and medium were quantified by
      ELISA based on detection of gamma-kappa complexes. Antibody produced by hairy
      roots was fully functional as demonstrated in bacterial aggregation assays which
      confirmed bivalent antigen-binding capacity. Eight antibody-producing hairy root
      clones retained their ability to produce mouse immunoglobulin over a period of 19
      months after transformation with Agrobacterium rhizogenes. For hairy roots grown
      in Gamborg's B5 medium, the maximum level of assembled antibody after 21-day
      culture in shake flasks was 18 mg L(-1) or 1.8% total soluble protein; up to 14%
      of the antibody was secreted into the medium. Antibody production by transgenic
      hairy roots had a negligible effect on growth compared with hairy roots of wild
      type tobacco. Antibody accumulation was growth associated with constant specific
      accumulation rate at the beginning of the culture; however, degradation of
      antibody was significant after 14 days and the amount of assembled antibody
      declined. Unlike hybridoma cultures, the time course of antibody accumulation by
      hairy roots showed a distinctive maximum very soon after the end of exponential
      growth. Total antibody levels were increased by addition of nitrate,
      polyvinylpyrrolidone, or gelatin to the medium. Polyvinylpyrrolidone and gelatin
      also markedly improved extracellular antibody concentrations; with these
      treatments, up to 43% of the antibody present was secreted into the medium.
      Antibody production was tested using hairy roots grown in an air-driven
      bioreactor. The intracellular antibody content after 30-day bioreactor culture
      was similar to that measured in shake flasks; however, the final extracellular
      antibody level was 1.7 times higher than the maximum measured in shake flasks.

PMID- 18634134
TI  - Kinetic studies of Chromobacterium viscosum lipase in AOT water in oil
      microemulsions and gelatin microemulsion-based organogels.
AB  - Kinetic studies have shown that octyl decanoate synthesis by Chromobacterium
      viscosum (CV) lipase in sodium bis-2-(ethylhexyl) sulfosuccinate (AOT) water in
      oil (w/o) microemulsions occurs via the nonsequential (ping-pong) bi bi
      mechanism. There was evidence of single substrate inhibition by decanoic acid at
      high concentrations. Initial rate data yielded estimates for acid and alcohol
      Michaelis constants of ca. 10(-1) mol dm(-3) and a maximum rate under saturation
      conditions of ca. 10(-3) mol dm(-3) s(-1) for a lipase concentration of 0.36 mg
      cm(-3). CV lipase immobilized in AOT microemulsion-based organogels (MBGs) was
      also found to catalyze the synthesis of octyl decanoate according to the ping
      pong bi bi mechanism. Reaction rates were similar in the free and immobilized
      systems under comparable conditions. Initial rates at saturating (but
      noninhibiting) substrate concentrations were first order with respect to CV
      lipase concentration in both w/o microemulsions and the MBG/oil systems.
      Gradients yielded an apparent k(cat) = 4.4 x 10(-4) mol g(-1) s(-1) in the case
      of w/o microemulsions, and 6.1 x 10(-4) mol g(-1) s(-1) for CV lipase immobilized
      in the MBGs. A third system comprising w/o microemulsions containing substrates
      and gelatin at concentrations comparable to those employed in the MBG
      formulations, provided a useful link between the conventional liquid
      microemulsion medium and the solid organogels. The nongelation of these
      intermediate systems stems from the early inclusion of substrate during a
      modified preparative protocol. The presence of substrate appears to prevent the
      development of a percolated microstructure that is thought to be a prerequisite
      for MBG formation. FT-NMR was employed as a semicontinuous in situ assay
      procedure. The apparent activity expressed by CV lipase in compositionally
      equivalent liquid and solid phase gelatin-containing systems was similar. An
      apparent activation energy of 24 +/- 2 kJ mol(-1) was determined by (1)H-NMR for
      esterification in gelatin-containing w/o microemulsions. This value agrees with
      previous determinations for CV lipase-catalyzed synthesis of octyl decanoate in
      "conventional" w/o microemulsions and MBG/oil systems. The similarities in lipase
      behavior are consistent with the claim, based largely on structural measurements,
      that the physico-chemical properties of the lipase-containing w/o microemulsion
      are to a large extent preserved on transformation to the daughter organogel. The
      close agreement of apparrent activation energies suggests that substrate mass
      transfer is not rate determining in the three studied systems.

PMID- 18634135
TI  - Ethanol-type fermentation from carbohydrate in high rate acidogenic reactor.
AB  - It has been found, in this study, that a new ethanol-type fermentation can be
      obtained in a continuous flow, high-rate acidogenic reactor receiving molasses as
      the feed. The operating pH must be maintained at about 4.5 to avoid onset of
      propionic fermentation. The acidogenic reactor had a VSS level of 20 g/L and its
      organic loading was as high as 80 to 90 kg COD/m(3) d. The operating ORP was
      around -250 mV. The ethanol-type fermentation was characterized by a simultaneous
      production of acetic acid and ethanol, while the yield of propionic was minimal
      even at a high organic loading rate of 80 to 90 kg COD/m(3) d, and also, the
      hydrogen partial pressure was as high as 50 kPa. Thus, this study has shown that
      the production of propionic acid is not always related to high hydrogen partial
      pressure. When the operating pH was increased to 5.5, the yield of propionic acid
      became significant.

PMID- 18634136
TI  - An integrated metabolic model for the aerobic and denitrifying biological
      phosphorus removal.
AB  - In this work, an integrated metabolic model for biological phosphorus removal is
      presented. Using a previously proposed mathematical model it was shown to be
      possible to describe the two known biological phosphorus removal processes, under
      aerobic and denitrifying conditions, with the same biochemical reactions, where
      only the difference in electron acceptor (oxygen and nitrate) is taken into
      account. Though, apart from the ATP/NADH ratio, the stoichiometry in those models
      is identical, different kinetic parameters were found. Therefore, a new kinetic
      structure is proposed that adequately describes phosphorus removal under
      denitrifying and aerobic conditions with the same kinetic equations and
      parameters. The ATP/NADH ratio (delta) is the only model parameter that is
      different for aerobic and denitrifying growth. With the new model, simulations of
      anaerobic/aerobic and anaerobic/denitrifying sequencing batch reactors (A(2) SBR
      and A/O SBR) were made for verification of the model. Not only short-term
      behavior, but also steady state, was simulated. The results showed very good
      agreement between model predictions and experimental results for a wide range of
      dynamic conditions and sludge retention times. Sensitivity analysis shows the
      influence of the model parameters and the feed substrate concentrations on both
      systems.

PMID- 18634137
TI  - Modeling and optimization in anaerobic bioconversion of complex substrates to
      acetic and butyric acids.
AB  - Cheese-processing wastewater was biologically treated to produce short-chain
      organic acids in laboratory scale continuously stirred tank reactors. A constant
      inoculum system was used to mimimize the experimental error due to the use of
      inconsistent inoculum. The inoculum system was operated with dilute cheese
      processing wastewater with 5000 mg soluble chemical oxygen demand/L at pH 6.5 and
      35 degrees C at 0.5 days hydraulic retention time. Response surface methodology
      was successfully applied to determine the optimum physiological conditions where
      the maximum rates of acetic and butyric acid production occurred. These were pH
      7.01 at 36.2 degrees C and pH 7.26 at 36.2 degrees C, respectively. The lack of
      overall predictability for butyric acid production meant that the response
      surface was much more complicated than that of acetic acid; therefore, a small
      change in pH or temperature could cause large variations in the response of
      butyric acid production.

PMID- 18634138
TI  - Use of flow field-flow fractionation for the rapid quantitation of ribosome and
      ribosomal subunits in Escherichia coli at different protein production
      conditions.
AB  - Asymmetrical flow field-flow fractionation was used for rapid (8-14 min)
      separation of ribosomes and their subunits. The amount of ribosomes and the mass
      fraction of ribosomes was determined in growing Escherichia coli cells. These
      quantities changed significantly at different growth phases. Ribosomal
      composition was monitored after the insertion of a protein-encoding plasmid and
      after the addition of an antibiotic agent. The results suggest that the method
      will be useful in studies of, e.g., the relationships between the protein
      production capacity of cells and the ribosomal composition. The analysis time is
      substantially shorter than ultracentrifugation run times.

PMID- 18634139
TI  - A mathematical model of the trafficking of acid-dependent enveloped viruses:
      application to the binding, uptake, and nuclear accumulation of baculovirus.
AB  - A quantitative understanding of virus trafficking would be useful in treating
      viral-mediated diseases, developing protocols for viral gene therapy, designing
      infection regimens for viral expression systems, and optimizing vaccine and
      recombinant protein production. Here, we present a mathematical model of the
      attachment, internalization, endosomal fusion, lysosomal routing, and nuclear
      accumulation of baculovirus in SF21 insect cells. The model accounts for
      multivalent bond formation of the virus with cell surface receptors. The model
      mimics accurately the experimental trafficking dynamics of the virus at both low
      and high virion to cell ratios, and estimates a receptor number of 11,000 per
      cell. A significant amount of virus was degraded intracellularly. Independent of
      the virion to cell ratio, half of the internalized virus was degraded with the
      rest accumulating in the nucleus. The formalism used in the model may be
      generally useful for other acid-dependent enveloped viruses. A subset of the
      model has been used previously to describe the trafficking of Semliki Forest
      virus, an acid-dependent enveloped RNA virus.Two pathways have previously been
      implicated for the in vitro entry of the budded form of the baculovirus:
      adsorptive endocytosis and plasma membrane fusion. Experimental evidence is
      presented which strongly suggests that the physical number of viruses entering by
      plasma membrane fusion is not significant relative to receptor-mediated
      endocytosis.

PMID- 18634140
TI  - Kinetics and response of a Pseudomonas fuorescens HK44 biosensor.
AB  - The reporter bacterium, Pseudomonas fluorescens HK44 (HK44), was characterized in
      an immobilized state to investigate utility for deployment as a remote sensor in
      the subsurface. A packed-bed reactor with alginate-immobilized HK44 simulated
      hydrodynamic conditions such as might be found in a subsurface environment. The
      reporter bacterium, HK44, harbors a reporter plasmid, pUTK21, which contains a
      transcriptional fusion between the nahG gene in the lower pathway of the
      catabolic plasmic NAH7 and a luxCDABE gene cassette. The upper nah pathway and
      the lux pathway in pUTK21 are induced by salicylate. The lux enzymes catalyze the
      light reaction. HK44 demonstrated a quantitative relationship between salicylate
      concentration and degradation. Light intensity mimicked salicylate concentration,
      whereas degradation was first order in biomass and first order in salicylate
      concentration, with a degradation constant of 2.23 x 10(-2) dm(3) g(-1) min(-1).

PMID- 18634141
TI  - A prospective study of magnetic resonance and radiographic imaging in relation to
      symptoms and clinical findings of the temporomandibular joint in children with
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: In patients with juvenile idiopathic arthritis (JIA) temporomandibular
      joint (TMJ) involvement is a common cause of severe growth disturbances. Extent
      of growth deviation depends on age of onset and duration of arthritis in the TMJ.
      TMJ arthritis is difficult to diagnose at an early stage since relatively few
      symptoms and clinical findings are related to this joint. The pathologic process
      can affect growth long before radiographic changes are seen. We investigated the
      relationship between TMJ arthritis and symptoms and clinical findings to suggest
      a clinical routine for diagnosing TMJ arthritis. We also describe the course of
      TMJ arthritis in relation to a commonly used radiographic method versus MRI.
      METHODS: Fifteen children with JIA were examined 4 times at 6 month intervals for
      TMJ involvement by clinical examination, MRI-scanning, and orthopantomograms
      (OPG). At baseline, 10 healthy children served as a control group. RESULTS:
      Patients reported more inability to chew and open their mouth than the control
      group. Translation of the condyle and range of mandibular movements were
      diminished in the arthritis group. Decreased translation was correlated to
      condylar changes seen on both OPG and MRI. MRI was superior to OPG in following
      changes of the condyle over time, and inflammation was detected in nearly all
      joints. CONCLUSION: OPG cannot be recommended for diagnosis or to follow the
      course of changes in the TMJ. We advocate recording condylar translation and
      mandibular range of motion as a current clinical routine to find early TMJ
      arthritis in contrast to the often used OPG performed in our study, which was an
      uncertain method.

PMID- 18634142
TI  - Dietary and lifestyle changes associated with high prevalence of hyperuricemia
      and gout in the Shandong coastal cities of Eastern China.
AB  - OBJECTIVE: To demonstrate the prevalence of hyperuricemia and gout associated
      with dietary and lifestyle changes and evaluate the implication of metabolic
      disorders to the development of hyperuricemia. METHODS: Data collected from 5,003
      subjects randomly recruited from 5 coastal cities (Qingdao, Rizhao, Yantai,
      Weihai, and Dongying) of Shandong province in Eastern China were analyzed.
      RESULTS: Overall, the prevalence for hyperuricemia and gout in the studied
      populations was 13.19% and 1.14%, respectively. The prevalence was significantly
      higher in men as compared to women (18.32% vs 8.56% for hyperuricemia, 1.94% vs
      0.42% for gout). Hyperuricemia was more common in men over age 30 and in women
      over age 50. A significant steady increase for the prevalence was noted as
      compared to the previous published data. Urban residents showed much higher
      prevalence of hyperuricemia as compared to rural residents (14.9% vs 10.1%, p =
      0.004). Similarly, higher prevalence was noted in the developed city compared to
      the less developed city (18.02 vs 5.3%). These discrepancies were highly
      correlated with economic development as manifested by the increase of daily
      consumption of meat and seafood. Additionally, alcohol, overweight or obesity,
      hypertension, and abnormal triglycerides were highly associated with higher
      prevalence of hyperuricemia. Moreover, hyperuricemia is likely a risk factor for
      the development of diabetes mellitus. CONCLUSION: There was a remarkable increase
      for the prevalence of hyperuricemia and gout, which is highly correlated with the
      development of the economy as manifested by dietary and lifestyle changes.

PMID- 18634143
TI  - Clinical features of hemophagocytic syndrome in patients with dermatomyositis.
AB  - OBJECTIVE: To investigate the clinical features of patients with dermatomyositis
      (DM) complicated by hemophagocytic syndrome (HPS). METHODS: Twenty-four patients
      diagnosed with DM and treated at our hospital between January 2002 and April 2007
      were enrolled for study. Serum levels of various parameters including cytokines
      were determined during the active disease states. RESULTS: Levels of serum
      ferritin, creatine kinase, and immune complexes were all significantly higher in
      all patients with HPS than in those without HPS. Levels of soluble interleukin-2
      receptor, macrophage colony stimulating factor, and the chemokine CX3CL1 were
      significantly elevated in DM patients with HPS. CONCLUSION: Our findings suggest
      that mechanisms related to both circulating immune complexes and circulating
      cytokines are involved in the pathogenesis of HPS complicating DM.

PMID- 18634144
TI  - Osteoarticular involvement in a series of 100 patients with sarcoidosis referred
      to rheumatology departments.
AB  - OBJECTIVE: To analyze the pattern of osteoarticular lesions in patients with
      sarcoidosis hospitalized in 4 rheumatology departments. METHODS: We carried out a
      systematic retrospective analysis of cases with sarcoidosis admitted in the last
      10 years, using hospital databases. Two distinct groups were defined from the
      outset: patients with Lofgren's syndrome (LS) or sarcoid rheumatism (SR). We
      assessed the following items: distribution of arthritis, chronicity, systemic
      manifestations, biochemical and immunological measures. RESULTS: We included 100
      patients (75% women); 43% had LS and 57% SR. Osteoarticular symptoms revealed the
      disease in 85% of patients. The patients in the LS group were younger than those
      in the SR group (41 +/- 9 vs 48 +/- 13 yrs; p < 0.006) and were more likely to
      have oligoarthritis involving ankles (58% vs 32%; p = 0.04) and high C-reactive
      protein concentrations (63% vs 33%; p < 0.005). Patients with SR presented
      osteoarticular symptoms in the form of oligoarthritis (32%), polyarthritis (32%),
      bony erosion in 8/57 (14%), and osteitis in 9/57 (16%). Lung interstitial
      involvement was more frequent in the SR group than in the LS group (38% vs 18%; p
      = 0.03). Chronic polyarthritis was associated with the detection of rheumatoid
      factor (p = 0.004). Osteitis occurred in older patients (p = 0.02). CONCLUSION:
      SR was the most frequent manifestation leading to hospitalization; it was
      characterized by oligoarthritis and polyarthritis and associated with
      interstitial lung involvement. Osseous involvement occurred in a quarter of SR
      patients with similar frequency of erosions targeting the distal small bones and
      osteitis. These latter occurred at a later age.

PMID- 18634145
TI  - Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a new mediator
      involved in early ankylosing spondylitis.
AB  - OBJECTIVE: To investigate the possible role of soluble triggering receptor
      expressed on myeloid cells-1 (sTREM-1) in ankylosing spondylitis (AS). METHODS:
      Serum sTREM-1 levels were measured in 80 patients with AS and 30 healthy
      controls, and synovial fluid (SF) sTREM-1 levels were tested in 6 AS patients
      using ELISA. Demographic data were collected, and patient's disease activity
      (BASDAI), functional ability (BASFI), and global assessment (BAS-G) were
      evaluated. We also tested erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), and IgA in these patients. RESULTS: Serum sTREM-1 levels were
      detectable (definition, > or = 15 pg/ml) in 31.3% (25/80) of the AS patients, as
      compared to only 10% (3/30) of healthy controls (p = 0.027). SF sTREM-1 levels
      were detectable (> or = 15 pg/ml) in 83% (5/6) of the AS patients. The detectable
      rate of sTREM-1 in SF was significantly higher than in serum (p = 0.018). Disease
      duration was shorter in AS patients with "higher" serum sTREM-1 levels (> or = 30
      pg/ml) versus those with "lower" levels (< 30 pg/ml) [mean (SD), 4.3 (3.7) vs 8.6
      (7.8) yrs, p = 0.036], but the differences between these 2 groups of patients
      were not evident based on results of BASDAI, BASFI, BAS-G, ESR, CRP, or IgA
      levels. Of note, serum sTREM-1 levels inversely correlated with disease duration
      (r = -0.433, p = 0.03) in the 25 AS patients with detectable sTREM-1 levels.
      CONCLUSION: sTREM-1 seems to be a new mediator involved in patients with AS,
      particularly in the early stages of disease.

PMID- 18634146
TI  - Toll-like receptor 4 and CD14 polymorphisms in ankylosing spondylitis: evidence
      of a weak association in Finns.
AB  - OBJECTIVE: To investigate the association of CD14 and Toll-like receptor (TLR4)
      with ankylosing spondylitis (AS). METHODS: A promoter variant in CD14 and 2
      coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS
      and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies
      was performed. RESULTS: In the Finnish study the CD14-260bp T variant showed an
      association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak
      association (global p = 0.03), with AS. No associations were seen in the UK based
      studies or in the metaanalyses. CONCLUSION: CD14 and TLR4 showed an association
      with AS in the Finns only.

PMID- 18634147
TI  - Prevalence of exercise pulmonary arterial hypertension in scleroderma.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a complication of scleroderma
      (systemic sclerosis, SSc); as soon as PAH develops, the patient's prognosis
      deteriorates rapidly. Early detection of PAH ensures timely treatment. We
      investigated the prevalence of exercise-induced PAH in a cohort of patients with
      SSc, and examined the relation between exercise-induced PAH and clinical
      characteristics and biochemical markers. METHODS: Patients with SSc and normal
      resting systolic pulmonary arterial pressure (sPAP) were studied. Eligible
      patients were asked to perform cycloergometer exercise until exhaustion, and
      exercise sPAP was measured. All patients had their pulmonary function tested and
      underwent echocardiography at rest. Brain natriuretic peptide (BNP) was also
      determined. RESULTS: Forty-one patients with SSc were studied. Mean sPAP at rest
      was 29.7 mm Hg, rising to a mean of 41.4 mm Hg on exercise. Eleven of 41 patients
      (26.8%) had sPAP post-exercise > 50 mm Hg and 8/41 (19.5%) > 55 mm Hg. A
      significant correlation was found between exercise sPAP and DLCO (p = 0.008) and
      between sPAP and BNP levels (p = 0.04). Pre-existing severe Raynaud's phenomenon
      was more prevalent (50% vs 20%), DLCO levels lower (78.9 vs 92.7 % predicted),
      and BNP levels higher (72.6 vs 42.1 pmol/ml) in patients with exercise sPAP > 55
      mm Hg. CONCLUSION: The prevalence of exercise-induced PAH in patients with
      scleroderma is high. Patients with lower DLCO and higher levels of BNP are at
      higher risk of developing higher sPAP. Studies with longterm followup are
      required to evaluate the risk of developing resting PAH in these patients.

PMID- 18634148
TI  - Color Doppler ultrasonography of hand and finger arteries to differentiate
      primary from secondary forms of Raynaud's phenomenon.
AB  - OBJECTIVE: Modern ultrasound (US) equipment allows rheumatologists to directly
      visualize hand and finger arteries. How does US aid in diagnosis of Raynaud's
      phenomenon (RP)? METHODS: Color Doppler US of the proper and common palmar
      digital, radial, and ulnar arteries and the superficial palmar arch of both hands
      was performed in 135 consecutive patients who presented with suspected RP.
      RESULTS: US was pathologic in 63% of patients with secondary RP, in 6% with
      primary RP, and in none with pseudo-RP (p < 0.0001). We found 3 types of vascular
      pathology: Type 1 showed narrowing or chronic occlusion of some proper digital
      arteries; Type 2 was characterized by the same finding in all proper digital
      arteries; and Type 3 involved acute occlusions. Type 1 was found in 3 of 53
      patients with primary RP and in 19 patients with secondary RP including 5 of 9
      patients with anti-centromere positive systemic sclerosis (SSc); Type 2 occurred
      in 16 patients with SSc, MCTD, and dermatomyositis; and Type 3 was found in 8
      patients with antiphospholipid antibody syndrome, thromboangiitis obliterans,
      vibration trauma, or vasculitis. The ulnar arteries were more commonly affected
      than the radial arteries. The 2nd radial, 3rd radial, 4th ulnar, and 5th ulnar
      proper palmar digital arteries were most commonly involved. CONCLUSION: Aiding in
      differentiating primary versus secondary RP, severe versus less severe disease,
      and acute versus chronic vascular occlusion, digital artery US depicts the same
      anatomical structures as angiography, but it is cheaper, faster, and noninvasive.

PMID- 18634149
TI  - Association of psoriasin (S100A7) with clinical manifestations of systemic
      sclerosis: is its presence in whole saliva a potential predictor of pulmonary
      involvement?
AB  - OBJECTIVE: To evaluate psoriasin (S100A7) expression in whole saliva (WS) of
      patients with diffuse systemic sclerosis (dSSc) and limited SSc (lSSc), and to
      correlate its presence with the different clinical manifestations of the disease.
      METHODS: Forty-four patients with limited or diffuse SSc were enrolled for study.
      WS proteins were separated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and psoriasin was identified by Western blot analysis using a
      specific polyclonal antibody. Patients with other rheumatic diseases with and
      without lung involvement were enrolled as pathological controls. Statistical
      analysis was performed to correlate each clinical manifestation with the presence
      of psoriasin. RESULTS: Three bands of 12, 24, and 50 kDa corresponding to
      monomeric and dimeric/multimeric forms of psoriasin were evidenced by immunoblot
      analysis in WS of 31 out of 44 patients with SSc (70.4%). In the other 13 WS
      samples, the 12 kDa band was totally absent, while the dimeric and multimeric
      bands were expressed at optical intensity (OD) levels comparable to the other
      samples. From a clinical point of view, the presence of 12 kDa monomeric
      psoriasin was significantly associated with SSc pulmonary involvement and with
      anti-Scl-70 antibody positivity. No control showed the psoriasin 12 kDa band.
      CONCLUSION: Our results identified salivary 12 kDa psoriasin as a potential
      predictor of pulmonary involvement in SSc. Thus, a psoriasin assay might be
      considered as a rapid, noninvasive, useful salivary biomarker for the detection
      of pulmonary involvement in SSc.

PMID- 18634150
TI  - Single nucleotide polymorphism of COL6A1 in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To investigate the genetic association between ankylosing spondylitis
      (AS) and single nucleotide polymorphisms (SNP) of collagen 6A1 gene (COL6A1), the
      candidate gene for ossification of the posterior longitudinal ligament. METHODS:
      One-hundred thirty Korean patients with AS (M: 116, F: 14, age: 29.0 +/- 4.6) and
      130 age- and sex-matched healthy subjects were recruited. The SNP of G365G,
      IVS15+39 C/T, IVS21+18 A/C by Snap shot assay and the SNP of IVS32-29T/C,
      IVS33+15G/A, IVS33+20A/G, and IVS33+55A/G by direct sequencing were genotyped and
      analyzed. Bonferroni correction was applied to multiple comparisons. RESULTS: The
      observed allelic frequencies for these SNP met Hardy-Weinberg equilibrium in all
      AS and controls. We also found an additional 2 SNP (R783Q and IVS33+88C/T) during
      direct sequencing. Therefore, a total of 9 SNP were analyzed in this study. There
      were no significant associations of allelic and genotype variations between AS
      and controls. The presence of uveitis was marginally associated with a haplotype
      (CC in G365G + IVS15+39 C/T). The variation of allele or haplotype of COL6A1 is
      not significantly associated with "more ossified disease." CONCLUSION: Because
      the genetic variations of COL6A1 could not be correlated with the occurrence of
      AS in Koreans, we conclude that despite common clinical features, AS and
      ossification of posterior longitudinal ligament are not genetically related, and
      the hyperostotic condition seen in the 2 diseases might be regulated differently.
      Further SNP of COL6A1 were not related to radiographic progression of AS.
      However, we found that the occurrence of uveitis might be related to the genetic
      variations of COL6A1 in patients with AS.

PMID- 18634151
TI  - No association between systemic sclerosis and C77G polymorphism in the human
      PTPRC (CD45) gene.
AB  - OBJECTIVE: The functional variant C77G (rs17612648) of PTPRC (CD45) was described
      to confer risk for systemic sclerosis (SSc) in German Caucasians. We analyzed
      this association in an independent, larger German cohort. METHODS: We genotyped
      171 cases and 179 controls. Cases were subgrouped according to sex, autoantibody
      profiles, or clinical subsets. RESULTS: No association of SSc with C77G was
      detected in the whole dataset, in subgroups, or in combined analyses with a
      previous study. CONCLUSION: The results do not confirm PTPRC C77G as a general
      and independent risk factor for development of SSc.

PMID- 18634152
TI  - Low versus high-dose iloprost therapy over 21 days in patients with secondary
      Raynaud's phenomenon and systemic sclerosis: a randomized, open, single-center
      study.
AB  - OBJECTIVE: We compared the efficacy of different dosages of longterm iloprost
      treatment on Raynaud's phenomenon (RP), ulcer healing, skin thickening, and
      progression of internal organ sclerosis in patients with systemic sclerosis
      (SSc). METHODS: Fifty patients with SSc were randomized 1:1 for the maximally
      tolerated dose up to 2 ng/kg body weight per minute or low-dose (0.5 ng/kg bw per
      min) intravenous iloprost administration, applied for 6 hours daily over 21 days.
      Effects on RP, ulcer healing, skin thickness, esophageal function, and lung
      involvement assessed by forced vital capacity (FVC) and DLCO were measured, as
      well as side effects. RESULTS: Both regimens yielded 70% reduction of digital
      ulcers, 40% reduction in frequency of RP, and 30% reduction in duration of RP.
      One year after therapy, the modified Rodnan skin score appeared to be unchanged.
      FVC and DLCO-SB were stable in 87% and 74% of the patients, respectively. The
      effect of iloprost on skin thickness and lung function was sustained in a
      subgroup of patients receiving several courses of iloprost. As assessed by a
      patient questionnaire, 12% of all patients did not respond to iloprost therapy,
      but 78% experienced a longlasting effect. Mild side effects were common in both
      groups, but did not lead to discontinuation of therapy. CONCLUSION: Low-dose
      iloprost was shown to be equally effective as high-dose iloprost in longterm
      treatment and was very effective in therapy of digital ulcers. Registered in
      www.ClinicalTrials.gov (registration no. NCT00622687).

PMID- 18634154
TI  - Cognitive function in a systemic lupus erythematosus inception cohort.
AB  - OBJECTIVE: Measurable cognitive impairment occurs in 30-75% of patients with
      systemic lupus erythematosus (SLE). We compared cognitive functioning in recently
      diagnosed SLE patients and normal controls. METHODS: The Automated
      Neuropsychological Assessment Metrics (ANAM), a repeatable computerized cognitive
      battery assessing cognitive processing speed and efficiency, was administered to
      111 recently diagnosed SLE patients and 79 normal controls. Throughput scores on
      ANAM subtests were compared using linear regression. RESULTS: After adjusting for
      age, gender, ethnicity, and education, SLE patients scored significantly lower
      than controls on throughput measures of 4 ANAM subtests: code substitution
      immediate recall (p = 0.02), continuous performance (p = 0.02), matching to
      sample (p = 0.02), and Sternberg subtest (p = 0.0002). CONCLUSIONS: Recently
      diagnosed SLE patients performed significantly worse than normal controls on 4 of
      9 ANAM subtests. ANAM subtests of cognitive efficiency requiring sustained
      attention/vigilance, visuospatial span of attention/working memory, and simple
      reaction time showed the greatest impairment. These cognitive deficits were
      particularly striking, because the SLE patients in this sample were not selected
      for the presence of neuropsychiatric manifestations, had mild SLE-related
      disease/damage, and were recently diagnosed with SLE. This suggests that deficits
      in cognitive efficiency and sustained attention are present early in the course
      of SLE and in the absence of other significant neuropsychiatric manifestations.

PMID- 18634153
TI  - The role of neighborhood and individual socioeconomic status in outcomes of
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine if neighborhood socioeconomic status (SES) is
      independently related to physical and mental health outcomes in systemic lupus
      erythematosus (SLE). METHODS: Data derived from the first 3 waves of the Lupus
      Outcomes Study, a telephone survey of 957 patients with confirmed SLE diagnoses,
      recruited from clinical and non-clinical sources. Residential addresses were
      geocoded to U.S. Census block groups. Outcome measures included the Systemic
      Lupus Activity Questionnaire (SLAQ) score, a self-reported assessment of SLE
      symptoms; the Medical Outcomes Study Short Form-36 Health Survey physical
      functioning score; and Center for Epidemiologic Studies-Depression (CES-D) score
      of > or = 19 points. Multivariate analyses adjusted for race/ethnicity and other
      demographic and health-related covariates. RESULTS: After adjustment, lower
      individual SES, measured by education, household income, or poverty status, was
      associated with all outcomes. In models that did not include individual SES, low
      neighborhood SES (> 30% of residents in poverty) was also associated with poor
      outcomes. After adjustment for individual SES, demographic, and health-related
      covariates, only CES-D > or = 19 remained associated with neighborhood SES: 47%
      [95% confidence interval (CI) 38-56%] versus 35% (95% CI 32-37%). CONCLUSION:
      Individual SES is associated with physical and mental health outcomes in persons
      with SLE. Low neighborhood SES contributes independently to high levels of
      depressive symptoms. Future research should focus on mechanisms underlying these
      differences.

PMID- 18634155
TI  - Decreased recent thymus emigrant number is associated with disease activity in
      systemic lupus erythematosus.
AB  - OBJECTIVE: T cell receptor excision circle (TREC) is produced during T cell
      maturation within the thymus, and the number of TREC-bearing cells reflects the
      proportion of recent thymic emigrants in the peripheral lymphocyte pool. We
      studied TREC levels in peripheral CD4+ and CD8+ lymphocytes in patients with
      systemic lupus erythematosus (SLE) with quiescent and with active disease and in
      age- and sex-matched healthy volunteers. METHODS: TREC levels in peripheral CD4+
      and CD8+ lymphocytes were determined in 29 patients with quiescent SLE, in 22
      with active disease, and in 31 age- and sex-matched healthy volunteers. The
      number of TREC/microg DNA was determined by real-time polymerase chain reaction
      gauged by a standard curve with known number of TREC-containing plasmids.
      RESULTS: TREC levels in CD4+ and CD8+ cells were lower in patients with active
      SLE (2.27 +/- 2.05 x 10(4) and 4.14 +/- 4.06 x 10(4) TREC/microg DNA,
      respectively) compared to quiescent SLE (5.83 +/- 7.41 x 10(4) and 11.24 +/-
      15.06 x 10(4) TREC/microg DNA; p = 0.03, p = 0.02, respectively). Patients with
      active SLE had lower TREC levels in CD4+ T cells than controls (2.27 +/- 2.05 x
      10(4) vs 5.64 +/- 4.99 x 10(4) TREC/microg DNA; p = 0.03), but this difference
      did not reach statistical significance for CD8+ cells (4.14 +/- 4.06 x 10(4) vs
      8.77 +/- 8.78 x 10(4) TREC/microg DNA; p = 0.1). Patients with quiescent SLE
      presented TREC levels similar to controls in CD4+ and CD8+ cells (p = 0.49, p =
      0.3, respectively). CONCLUSION: Our results reveal decreased TREC levels in the
      peripheral blood of patients with active but not in patients with quiescent SLE.
      These data suggest that TREC levels are affected by disease activity in SLE.

PMID- 18634156
TI  - Novel cardiovascular risk factors in premature coronary atherosclerosis
      associated with systemic lupus erythematosus.
AB  - OBJECTIVE: Several mediators of inflammation are associated with atherosclerotic
      cardiovascular disease in the general population, but their relationship to
      accelerated atherosclerosis associated with an inflammatory disease such as
      systemic lupus erythematosus (SLE) is not known. METHODS: We compared
      concentrations of cytokines (TNF-alpha, IL-1alpha, and VEGF), inflammatory
      enzymes (MPO and MMP-9), acute-phase reactants (ESR, CRP, and SAA) and adhesion
      molecules (VCAM, ICAM, and E-selectin) in 109 patients with SLE and 78 controls.
      The relationship between inflammatory markers and coronary atherosclerosis
      detected as calcified plaque by electron beam CT was determined in patients with
      SLE. RESULTS: Concentrations of all markers of inflammation other than VCAM, MMP
      9, and IL-1alpha were significantly higher in SLE. In multivariable analyses
      adjusting for Framingham risk score, cumulative corticosteroid dose, and
      diabetes, E-selectin (OR 1.90, 95% CI 1.08-3.33), VCAM (OR 1.99, 1.18-3.37), ICAM
      (OR 2.30, 1.13-4.7), and TNF-alpha (OR 2.36, 1.10-5.06) were significantly
      associated with the severity of coronary calcium. CONCLUSION: Concentrations of
      adhesion molecules and TNF-alpha are associated with coronary atherosclerosis in
      SLE independent of the Framingham risk score.

PMID- 18634157
TI  - Upregulation of antiphospholipid antibodies following cyclophosphamide therapy in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: We have observed several cases of patients with systemic lupus
      erythematosus (SLE) who developed antiphospholipid antibodies (aPL) or full blown
      antiphospholipid syndrome (APS) after being successfully treated with
      cyclophosphamide (CYC). To further evaluate the significance of this phenomenon
      we undertook a retrospective study of our patient population with SLE. METHODS:
      The charts of 320 patients with SLE, either CYC treated (n = 117) or non-treated
      (n = 203), were reviewed. The disease activity over time was evaluated using the
      European Consensus Lupus Activity Measurement (ECLAM) scoring system, as well as
      initial and cumulative anti-dsDNA antibody titers and C3, C4 complement levels.
      aPL titers (IgG and IgM) were documented for all patients. Seroconversion was
      defined as the de novo appearance of aPL antibodies at a titer higher than the
      99th percentile of 100 normal sera, tested on 2 occasions 12 weeks apart.
      RESULTS: Seroconversion occurred in 22 out of 117 patients treated with CYC as
      compared with 2 out of 203 non-CYC treated patients [odds ratio (OR) = 23.27, 95%
      confidence interval (CI) 5.36-101.01]. Six patients from the seroconverted CYC
      treated group were diagnosed with APS compared to none in the non-CYC treated
      group. The association between seroconversion and CYC remained significant after
      adjustment for ECLAM score after treatment, prednisone dose and disease duration
      (OR = 13.4, 95% CI 2.67-67.50). Seroconversion occurred despite successful
      disease remission as judged by significant decrease of: anti-dsDNA antibody
      titers (p < 0.01), ECLAM scores (p < 0.01), and C3 (p < 0.01) and C4 levels (p <
      0.01). CONCLUSION: Our data suggest that CYC therapy might be associated with
      upregulation of aPL and development of antiphospholipid syndrome despite
      suppression of SLE activity.

PMID- 18634158
TI  - Effects of prasterone on bone mineral density in women with active systemic lupus
      erythematosus receiving chronic glucocorticoid therapy.
AB  - OBJECTIVE: To assess prevention of bone mineral density (BMD) loss and durability
      of the response during treatment with prasterone in women with systemic lupus
      erythematosus (SLE) receiving chronic glucocorticoids. METHODS: 155 patients with
      SLE received 200 mg/day prasterone or placebo for 6 months in a double-blind
      phase. Subsequently, 114 patients were re-randomized to receive 200 or 100 mg/day
      prasterone for 12 months in an open-label phase. Primary efficacy endpoints were
      changes in BMD at the lumbar spine (L-spine) from baseline to Month 6 and
      maintenance of BMD from Month 6 to 18 for patients who received prasterone during
      the double-blind phase. RESULTS: In the double-blind phase, there was a trend for
      a small gain in BMD at the L-spine for patients who received 200 mg/day
      prasterone for 6 months versus a loss in the placebo group (mean +/- SD, 0.003 +/
      0.035 vs -0.005 +/- 0.053 g/cm(2), respectively; p = 0.293 between groups). In
      the open-label phase, there was dose-dependent increase in BMD at the L-spine at
      Month 18 between patients who received 200 versus 100 mg/day prasterone (p =
      0.021). For patients who received 200 mg/day prasterone for 18 months, the L
      spine BMD gain was 1.083 +/- 0.512% (p = 0.042). There was no overall change in
      BMD at the total hip over 18 months with 200 mg/day prasterone treatment. The
      safety profile reflected the weak androgenic properties of prasterone.
      CONCLUSION: This study suggests prasterone 200 mg/day may offer mild protection
      against bone loss in women with SLE receiving glucocorticoids.
      (ClinicalTrials.gov Identifiers NCT00053560 and NCT00082511).

PMID- 18634159
TI  - Predictors of discontinuation of tumor necrosis factor inhibitors in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF) inhibitors have transformed
      management of rheumatoid arthritis (RA); however, many patients discontinue TNF
      inhibitors. Our goal was to determine the discontinuation rate of TNF inhibitors
      and identify predictors associated with discontinuation. METHODS: Enrollees in
      the Brigham RA Sequential Study (BRASS) formed the eligible cohort. Patients
      reporting use of a TNF inhibitor with at least 6 months of followup were followed
      until reporting TNF inhibitor discontinuation or their last study visit if they
      continued therapy. Potential predictor variables, including demographic and
      clinical data assessed at baseline and 6 months prior to study endpoint, were
      identified using a Cox proportional regression. RESULTS: Among 961 patients in
      BRASS, 503 were using a TNF inhibitor with at least 6 months of followup in BRASS
      (mean length of followup 39 mo, SD 13). Two hundred ten patients (42%) reported
      discontinuation of TNF inhibitor. Higher physician global scores (hazard ratio
      1.27, 95% CI 1.18-1.38) and RA Disease Activity Index scores (HR 1.13, 95% CI
      1.05-1.22) 6 months prior to stopping the TNF inhibitor and higher number of TNF
      inhibitors used previously (HR 1.30, 95% CI 1.03-1.66) were associated with
      discontinuation of TNF inhibitor. Prior use of synthetic disease modifying
      antirheumatic drugs (HR 0.50, 95% CI 0.34-0.72) and more years of cumulative
      methotrexate use (HR 0.24, 95% CI 0.12-0.47) were inversely associated with
      discontinuation of TNF inhibitor. CONCLUSION: These data demonstrate that a
      significant number of patients with RA discontinue TNF inhibitors. Several easily
      characterized clinical variables have a modest predictive association with
      reduced probability of TNF inhibitor discontinuation.

PMID- 18634160
TI  - Risk of development of lung cancer is increased in patients with rheumatoid
      arthritis: a large case control study in US veterans.
AB  - OBJECTIVE: To investigate the occurrence of lung cancer in patients with
      rheumatoid arthritis (RA) in the US veteran population. Patients with rheumatic
      diseases appear to have an increased risk for the development of
      lymphoproliferative and some solid organ malignancies. METHODS: We conducted a
      retrospective case control study using prospectively collected data from the
      Veterans Integrated Service Networks (VISN) 16 Veteran Affairs (VA) database from
      1998 to 2004. We studied the association of RA and lung cancer and analyzed data
      on 483,721 VA patients. Patients were identified by searching for the diagnoses
      of RA and lung cancer based on the International Classification of Diseases (ICD)
      codes. We identified 8768 (1.81%) patients with a diagnosis of RA (ICD code
      714.0), 7280 (1.5%) patients with lung cancer (ICD code 162.0), 247 patients with
      lung cancer and RA, and 7033 patients with lung cancer but no RA. Logistic
      regression analysis was performed to adjust for age, gender, race, and tobacco
      and asbestos exposure. Statistical tests were conducted at a 5% level of
      significance. RESULTS: The diagnosis of RA was determined to have a significant
      association with lung cancer in this veteran population. Patients with RA are 43%
      (odds ratio 1.43) more likely to develop lung cancer than patients without RA,
      when adjusted for covariates. CONCLUSION: Our study shows a significant positive
      association between RA and the development of lung cancer in the veteran
      population. Veterans with RA have an increased incidence of lung cancer when
      compared to the non-RA population.

PMID- 18634161
TI  - Tumor necrosis factor-alpha -1031 T/C polymorphism is associated with smaller and
      more proatherogenic low density lipoprotein particles in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To study, in patients with rheumatoid arthritis (RA), the association
      between the tumor necrosis factor (TNF)-alpha -1031 T/C polymorphism and
      quantitative and qualitative low density lipoprotein (LDL) characteristics.
      METHODS: From a sample of 100 patients with RA and 100 controls, we used the
      strategy of "recruit by genotype" to select 30 patients with RA: 15 carriers of
      the rare allele (C) and 15 homozygous for the more frequent allele (T). These
      were matched with 30 controls. Plasma lipoprotein profile including size
      distribution of lipoproteins was determined using nuclear magnetic resonance
      spectrometry. LDL susceptibility to oxidation was assessed by diene formation.
      The LDL affinity for extracellular matrix was determined using electrophoretic
      mobility shift assay. Genotyping was performed by SnapShot. RESULTS: Compared to
      TT patients with RA, carriers of the C allele had (1) LDL particles significantly
      smaller [20.74 (0.68) nm vs 21.18 (0.52), p < 0.02]; (2) LDL particles with a
      greater affinity for the proteoglycans (i.e., with a lower Kd) [197.26 (123.98)
      nmol/l vs 259.26 (139.31), p = 0.05]; and (3) LDL particles with significantly
      greater susceptibility to oxidation [shorter lag phase: 47 (20.01) min vs 74
      (41.8), p < 0.03, and higher maximal rate of diene production: 3.1 (0.5) mol/min
      vs 2.6 (0.95), p < 0.05]. None of these differences was observed in the control
      group. CONCLUSION: In patients with RA, genetic variability in the TNF-alpha gene
      is associated with smaller LDL particles that have a greater affinity for
      extracellular matrix and higher susceptibility to oxidation. Because these
      characteristics are associated with a greater risk of atherosclerosis,
      identification of such predisposition in patients with RA could help in
      implementing early preventive intervention measures against cardiovascular
      disease.

PMID- 18634162
TI  - Patients with rheumatoid arthritis treated with methotrexate (MTX):
      concentrations of steady-state erythrocyte MTX correlate to plasma concentrations
      and clinical efficacy.
AB  - OBJECTIVE: To investigate the accumulation of methotrexate (MTX) in circulating
      erythrocytes and the association with pharmacokinetic variables, weekly dose, and
      clinical efficacy in 2 cohorts of patients with chronic active rheumatoid
      arthritis (RA) undergoing MTX monotherapy. METHODS: Seventy-six patients with RA
      were included in this open prospective study: 40 were included before initiation
      of MTX therapy. Laboratory analyses, intracellular MTX concentrations in
      erythrocytes (Ery-MTX), and clinical examinations including toxicity data were
      performed prospectively for 52 weeks. Plasma concentrations of MTX were measured
      and area under the plasma concentration versus time curve (AUC) was estimated
      along with other pharmacokinetic variables in a population based software model.
      RESULTS: Ery-MTX rose after initiation of therapy and reached a steady state
      after 6-8 weeks. The correlation between steady-state Ery-MTX and dose was poor
      (r(2) = 0.16), whereas steady-state Ery-MTX levels correlated strongly with the
      estimated AUC (r(2) = 0.51, log-transformed variables). Both steady-state Ery-MTX
      levels and estimated AUC were significantly higher in patients responding to MTX
      therapy than in patients classified as nonresponders according to American
      College of Rheumatology core criteria and were similar to patients on longterm
      MTX therapy. CONCLUSION: Our results indicate that clinical efficacy and Ery-MTX
      may have a causal relation and that measurement of Ery-MTX or estimation of AUC
      in a software model provides useful guidelines to the clinician when starting MTX
      therapy in patients with RA. The latter can be performed immediately after
      initiation of therapy.

PMID- 18634163
TI  - Effect of anakinra on functional status in patients with active rheumatoid
      arthritis receiving concomitant therapy with traditional disease modifying
      antirheumatic drugs: evidence from the OMEGA Trial.
AB  - OBJECTIVE: To assess changes in functional status in patients with rheumatoid
      arthritis (RA) receiving the interleukin-1 receptor antagonist anakinra in
      addition to a disease modifying antirheumatic drug (DMARD). METHODS: In this
      large, multicenter, open-label, single-arm study, adult patients with RA
      receiving methotrexate, sulfasalazine, or hydroxychloroquine for > or = 3 months
      were given anakinra 100 mg once daily for up to 36 weeks. The primary objective
      was to evaluate changes from baseline to week 36 in the Health Assessment
      Questionnaire (HAQ) disability index and subscales. Changes in the 28-joint
      Disease Activity Score (DAS28), proportion of patients meeting European League
      Against Rheumatism (EULAR) response criteria, and the safety of each combination
      regimen were also assessed. RESULTS: A total of 1207 patients were enrolled,
      received > or = 1 dose of anakinra, and were included in the efficacy and safety
      analyses. A statistically significant change in the HAQ disability index was
      observed (p = 0.0001); no significant differences were seen among the 3 DMARD
      groups. A clinically meaningful improvement in HAQ (> 0.22) was observed in 51%
      of patients. Mean improvement in DAS28 was 1.5 (p < 0.0001), and 64% of patients
      achieved a good or moderate EULAR response score. Injection site reaction was the
      most frequently (62%) reported adverse event. The incidence of infections (24%),
      most commonly respiratory infection, was similar across treatment groups. No
      notable changes were observed in laboratory findings and vital signs. CONCLUSION:
      These findings indicate that anakinra 100 mg/day in combination with DMARD
      therapy safely improved functional status in patients with active RA.

PMID- 18634164
TI  - Cost-effectiveness of abatacept in patients with moderately to severely active
      rheumatoid arthritis and inadequate response to tumor necrosis factor-alpha
      antagonists.
AB  - OBJECTIVE: To assess cost-effectiveness of abatacept in patients with rheumatoid
      arthritis (RA) with inadequate response to tumor necrosis factor-alpha
      antagonists (anti-TNF). METHODS: We developed a simulation model to depict
      progression of disability [in terms of Health Assessment Questionnaire Disability
      Index (HAQ-DI)] in women aged 55-64 years with moderately to severely active RA
      and inadequate response to anti-TNF. At model entry, patients were assumed to
      receive either oral disease modifying antirheumatic drugs (DMARD) only or oral
      DMARD plus abatacept. Patients were then tracked from model entry until death.
      Future health-state utilities and medical-care costs (except study therapy) were
      estimated based on predicted values of the HAQ-DI. The model was estimated using
      data from a Phase III clinical trial of abatacept plus secondary sources. Cost
      effectiveness was expressed in terms of incremental cost (2006 US$) per quality
      adjusted life-year (QALY) gained alternatively over 10 years and a lifetime.
      Future costs and health effects were discounted at 3% annually. RESULTS: Over 10
      years, abatacept would yield 1.0 additional QALY (undiscounted) per patient (4.0
      vs 3.0 for oral DMARD) at an incremental (discounted) cost of $45,497 (100,648 vs
      $55,151) respectively; over a lifetime, corresponding figures were 1.6 QALY (5.8
      vs 4.2) and $64,978 ($140,714 vs $82,489). Cost-effectiveness was [mean (95% CI)]
      $50,576 ($47,056, $54,944) per QALY gained over 10 years, and $45,979 ($42,678,
      $49,932) per QALY gained over a lifetime. Findings were robust in sensitivity
      analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical
      practice in patients with moderately to severely active RA and inadequate
      response to an anti-TNF.

PMID- 18634165
TI  - Risk factors associated with acute hip prosthetic joint infections and outcome of
      treatment with a rifampin-based regimen.

PMID- 18634167
TI  - Different approaches to assessing occupational exposure. Editorial.

PMID- 18634166
TI  - Zolpidem dependence. Zolpidem dependence is frequent, and should be discussed
      with patients.

PMID- 18634168
TI  - Ball State conducts usability study on bedside computer system.

PMID- 18634170
TI  - Federal government extends bandwidth freeze through 2005.

PMID- 18634169
TI  - Health information technology plan aims to reduce medical errors.

PMID- 18634171
TI  - Underwater simulation to test limits, benefits of telemedicine.

PMID- 18634172
TI  - Implementing Citrix: weighing the pros and cons.

PMID- 18634173
TI  - A natural partnership: clinical engineering and information technology.

PMID- 18634174
TI  - Analyzing the return on investment for indoor positioning systems.

PMID- 18634175
TI  - The PACS initiative: what does it take?
AB  - Successful implementation of a PACS requires both a technology infusion and a re
      engineering of the film-based workflow used for more than 100 years in health
      care. Because of the sensitivity of a PACS, high-level administrative support is
      needed to address resistance to change and other roadblocks. A PACS project team
      must look at how the system will operate not only in the primary imaging
      department, but also throughout the health care institution. The project plan
      developed must take into account the technology and workflow changes required,
      the potential risks to the project, and key milestones that must be met. Frequent
      ongoing review of the project at a high level is required. Technology enables
      PACS to improve workflow, and that technology encompasses modalities, networks,
      diagnostic workstations, archives, interfaces, Web distribution, and other
      systems (i.e. RIS, HIS). Support from information technology and clinical
      engineering departments, PACS vendors, modality original equipment manufacturers
      (OEMs), and third-party software is required. Adopting PACS means dependency on
      this technology. Improvements realized via PACS become every day expectations;
      therefore, PACS must have operational support and documented downtime procedures.
      The potential benefits of PACS-instant, multiple-user accessibility to high
      resolution imagery-promise hospitals a significant return on investment.

PMID- 18634176
TI  - Looking ahead: using technology to improve patient safety.

PMID- 18634177
TI  - Ocular manifestations of neurofibromatosis 1 - m. Recklinghausen.
AB  - Neurofibromatosis type 1 (NF 1) - morbus von Recklinghausen is an autosomal
      dominant phacomatosis with variable expression. The gene for NF 1 is located on
      chromosome 17q11.2. Incidence is 1 in 3500 live births. The diagnosis is made on
      the basis of clinical manifestations. Diagnosis requires the presence of 2 or
      more major criteria: 6 or more cafe au lait spots, 2 or more cutaneous
      neurofibromas or 1 plexiform neurofibroma, an optic nerve glioma, 2 or more iris
      Lisch nodules, axillary or inguinal freckling, bony lesions--pseudoarthrosis,
      sphenoid wing hypoplasia, or a first-degree relative with NF 1.

PMID- 18634178
TI  - The World Medical Association statement on HIV/AIDS and the medical profession.

PMID- 18634179
TI  - [Basis for clinical economics].

PMID- 18634180
TI  - [Parental environment alters gene expression of the child during fetal and
      infantile stages: life score approach and epigenetics].

PMID- 18634181
TI  - [Exercise, physical activities and public health (3). For good quality of life
      leading to long healthy life].

PMID- 18634182
TI  - [Commentary to the article: Di Mario C, Dudek D, Piscione F, et al.; CARESS-in
      AMI (Combined Abciximab RE-teplase Stent Study in Acute Myocardial Infarction)
      Investigators. Immediate angioplasty versus standard therapy with rescue
      angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in
      Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised,
      multicentre trial. Lancet 2008; 371: 559-68].

PMID- 18634183
TI  - [The social identity and culture of Toulouse architect Urbain Vitry (1802-63) as
      seen through testamentary documents].

PMID- 18634184
TI  - [Social welfare and government in the city of Buenos Aires, 1821-61].

PMID- 18634188
TI  - Preface. The first collection of scientific studies on Tai Chi Chuan.

PMID- 18634185
TI  - Shipboard revolts, African authority, and the Atlantic slave trade.

PMID- 18634189
TI  - "The abandoned mother": ageing, old age and missionaries in early and mid
      nineteenth-century South-east Africa.

PMID- 18634190
TI  - [Commentary to the article: Wiviott S D, Braunwald E, McCabe C H et al. Prasugrel
      versus clopidogrel in patients with acute coronary syndrome. N Engl J Med 2007;
      357: 2001-15].

PMID- 18634191
TI  - [Britain and the establishment of the "rule of law" for Sino-Western trade at
      treaty ports between the two Opium Wars].

PMID- 18634192
TI  - Bioenergetics: energy conservation and conversion . Introduction.

PMID- 18634193
TI  - "Mulato entre negros" (y blancos): writing, race, the antislavery question, and
      Juan Francisco Manzano's autobiografia.

PMID- 18634194
TI  - The homestead and the garden plot: cultural pressures on land reform in
      nineteenth-century Britain and the USA.

PMID- 18634195
TI  - The correspondence between Louis Agassiz and the French naturalists Georges
      Cuvier, Lucien Bonaparte and Alexandre Brongniart in the manuscript collections
      of the Museum National d'Histoire Naturelle and Institut de France.

PMID- 18634197
TI  - [History and daily life: "fevers" and public health. The annus horribilis in Rio
      de Janeiro].

PMID- 18634198
TI  - Protein-protein interactions as new drug targets. Preface.

PMID- 18634199
TI  - Orphan G protein-coupled receptors and novel neuropeptides. Introduction.

PMID- 18634200
TI  - FluMist: refrigerated, never frozen.

PMID- 18634201
TI  - A better staging system for pressure ulcers.

PMID- 18634202
TI  - Updated guidelines for evaluating public health surveillance systems:
      recommendations from the Guidelines Working Group.
AB  - The purpose of evaluating public health surveillance systems is to ensure that
      problems of public health importance are being monitored efficiently and
      effectively. CDC's Guidelines for Evaluating Surveillance Systems are being
      updated to address the need for a) the integration of surveillance and health
      information systems, b) the establishment of data standards, c) the electronic
      exchange of health data, and d) changes in the objectives of public health
      surveillance to facilitate the response of public health to emerging health
      threats (e.g., new diseases). This report provides updated guidelines for
      evaluating surveillance systems based on CDC's Framework for Program Evaluation
      in Public Health, research and discussion of concerns related to public health
      surveillance systems, and comments received from the public health community. The
      guidelines in this report describe many tasks and related activities that can be
      applied to public health surveillance systems.

PMID- 18634203
TI  - Detection of spotted fever and typhus group rickettsial infection in wild raccoon
      dogs (Nyctereutes procyonoides koreensis) in Chonbuk Province, Korea.
AB  - Both the spotted fever and the typhus group rickettsioses are potential emerging
      arthropod-borne infectious disease complexes in Korea. Wild raccoon dogs
      (Nyctereutes procyonoides koreensis) sheltered at the Korean Society for the
      Protection of Wild Animals, Chonbuk Branch, Korea, were sampled for the presence
      of spotted fever and typhus group rickettsial pathogens. Thirty-six serum samples
      of wild raccoon dogs were examined by an indirect fluorescent antibody test using
      type-specific YH strain Rickettsia japonica (spotted fever group rickettsia) and
      Wilmington strain Rickettsia typhi (typhus group rickettsia). The prevalence of
      sera that were seropositive was 30.5% (11/36) for the spotted fever group and
      41.6% (15/36) for the typhus group. Five samples were seropositive for both
      antigens. This study is first to demonstrate rickettsial antibodies in wild
      raccoon dogs, and it provides seroepidemiologic evidence of the endemic presence
      of rickettsial agents in Korea.

PMID- 18634204
TI  - A visual health assessment of captive Asian elephants (Elephas maximus) housed in
      India.
AB  - A visual health assessment and survey questionnaire was conducted on 81 Asian
      elephants (Elephas maximus) housed in 10 animal facilities throughout India
      between November 2004 and February 2005. The survey questionnaire consisted of 10
      questions that evaluated the health of the elephants, and they were completed
      after visually assessing each individual elephant. The information collected was
      ranked on a scale that was used to statistically compare the health among the
      study subjects. This study documented that 43.21% of the captive elephants
      surveyed exhibited hyperkeratosis. A significant proportion of the elephants
      owned by tourist camps had poor skin condition when compared with elephants from
      zoos and at a forest camp. Similarly, captive-born individuals were found to have
      better skin condition than animals that were caught from the wild. Sixty (74.1%)
      of the captive elephants that were observed during this study had fissures in
      their footpads, 20% of which were severe. The prevalence of foot fissures was
      significantly higher in females. A greater proportion of elephants owned by
      tourist camps displayed vertical and horizontal toenail cracks in comparison with
      the forest camp and zoo elephants. It was noted that 76.9% of the wounded animals
      and 80% of those having abscesses were housed at temples and tourist camps. Also,
      approximately 8.5% of the captive elephant population observed during this study
      had eye-related problems, and they were all housed at temples and tourist camps.
      In conclusion, it was evident that elephants housed at temples or tourist camps
      exhibited poor skin condition with wounds and abscesses. These findings suggest
      that the overall condition of the elephants housed at tourist camps was poor
      compared with elephants housed at zoos and at the forest camp.

PMID- 18634205
TI  - Treatment factors influencing the use of recombinant platelet-derived growth
      factor (Regranex) for head and lateral line erosion syndrome in ocean surgeonfish
      (Acanthurus bahianus).
AB  - The clinical efficacy of becaplermin (Regranex, Ortho-McNeil Pharmaceutical,
      Inc., Raritan, New Jersey 08869) on head and lateral line erosion syndrome
      (HLLES) in ocean surgeonfish (Acanthurus bahianus) was examined in a two-part
      study to determine suitable application frequencies of the drug and the effects
      of the environment on outcome of treatments. In the first part of the study, 12
      ocean surgeonfish with prior HLLES were equally divided into three treatment
      groups, varying in application frequency of becaplermin: 1) one application, 2)
      three applications every 3 wk, and 3) no applications. After 9 wk, it was
      determined through photograph and computer analysis that fish treated with
      becaplermin did heal significantly more than the fish that were not treated. No
      significant difference was found when comparing the two treatment regimes;
      therefore, a one-time treatment of becaplermin was just as effective as the three
      time application, reducing cost of the treatment, staff labor, and stress to the
      animals. In the second part of the study, the effect of the water environment on
      HLLES development was documented before and after a one-time treatment of
      becaplermin. When fish were treated and placed into a system known to cause
      HLLES, the becaplermin treatment had no effect on reducing the HLLES progression,
      whereas treated fish that were placed into a system that did not cause HLLES
      showed a significant decrease in erosion after the treatment. Therefore, treating
      fish being placed into a HLLES-causing system serves no beneficial purpose to
      healing HLLES.

PMID- 18634206
TI  - Yolk coelomitis in Fiji Island banded iguanas (Brachylophus fasciatus).
AB  - Yolk coelomitis is a major cause of death in captive sexually mature female Fiji
      Island banded iguanas (Brachylophus fasciatus) maintained by the Zoological
      Society of San Diego. The medical records, breeding histories, and pathology
      archival materials from this group were reviewed to study this health problem.
      From 1987 through 2004, deaths of nine of 21 adult females were due to yolk
      coelomitis. Most iguanas had a history of reproduction-related problems, which
      included reproductive failure, episodes of lethargy associated with ovarian
      activity, folliculostasis, ovostasis, and behavioral abnormalities. Most affected
      iguanas either were found dead or presented moribund and subsequently died or
      were euthanized. Clinical signs were nonspecific and included lethargy, cutaneous
      discoloration, and coelomic effusion. Yolk leakage in most cases was associated
      with the presence of large vitellogenic follicles undergoing atresia and resulted
      in coelomitis characterized by florid mesothelial proliferation.

PMID- 18634207
TI  - Refinement of a commercial bench-top relaxin assay for pregnancy diagnosis using
      urine from domestic and nondomestic felids.
AB  - Relaxin, a 6-kDa polypeptide hormone, is excreted in the urine during pregnancy
      in several mammalian species. A recent study showed that detection of urinary
      relaxin using a bench-top serum assay (Witness relaxin kit, Synbiotics Corp., San
      Diego, California 92127, USA) can be diagnostic for pregnancy in domestic cats
      (Felis silvestris catus), but it is unknown whether the bench-top kit is
      applicable with urine across felid species. Our objectives were to 1) examine
      modifications in urine processing to improve kit reliability in pregnant cats, 2)
      evaluate the impact of concentrating urine via filtration on relaxin detection,
      3) assess the effect of sample freezing on relaxin concentrations, and 4) begin
      quantifying urinary relaxin levels in nondomestic felids. Urine and serum were
      collected from domestic cats and nondomestic cat species (Pallas' cat, Otocolobus
      manul; sand cat, Felis margarita; cheetah, Acinonyx jubatus; and lion, Panthera
      leo) at several times after breeding. Urine samples, subjected to various
      processing methods, were tested using the bench-top kit, and relaxin levels were
      later quantified via radioimmunoassay. For domestic cat urine samples, filtration
      and addition of protein/phosphate buffer improved the consistency of the relaxin
      kit for early pregnancy diagnosis. Urine freezing caused a slight (approximately
      13%) but significant decrease in relaxin concentrations, but frozen-thawed
      samples still tested positive with the bench-top kit. In nondomestic felids,
      urinary relaxin immunoreactivity during pregnancy was similar to or higher than
      that of pregnant domestic cats, suggesting that relaxin is a reliable cross
      species marker of pregnancy. Urinary relaxin was detectable using the bench-top
      kit in pregnant Pallas' cats, but urine samples from other species tested
      negative, regardless of processing methods. Findings suggest that measurement of
      urinary relaxin is a promising approach for noninvasive pregnancy diagnosis in
      exotic felids, but further assessment of urinary relaxin profiles among cat
      species and modification of the bench-top relaxin kit are warranted to improve
      cross-species utility.

PMID- 18634208
TI  - Comparison of blood aminotransferase methods for assessment of myopathy and
      hepatopathy in Florida manatees (Trichechus manatus latirostris).
AB  - Muscle injury is common in Florida manatees (Trichechus manatus latirostris).
      Plasma aspartate aminotransferase (AST) is frequently used to assess muscular
      damage in capture myopathy and traumatic injury. Therefore, accurate measurement
      of AST and alanine aminotransferase (ALT) is important in managed, free-ranging
      animals, as well as in those rehabilitating from injury. Activities of these
      enzymes, however, are usually not increased in manatees with either acute or
      chronic muscle damage, despite marked increases in plasma creatine kinase
      activity. It is hypothesized that this absence of response is due to apoenzymes
      in the blood not detected by commonly used veterinary assays. Addition of
      coenzyme pyridoxal-5-phosphate (P5P or vitamin B6) should, therefore, result in
      higher measured enzyme activities. The objective of this study was to determine
      the most accurate, precise, and diagnostically useful method for aminotransferase
      measurement in manatees that can be used in veterinary practices and diagnostic
      laboratories. Additionally, appropriate collection and storage techniques were
      assessed. The use of an optimized commercial wet chemical assay with 100 micromol
      P5P resulted in a positive bias of measured enzyme activities in a healthy
      population of animals. However, AST and ALT were still much lower than that
      typically observed in domestic animals and should not be used alone in the
      assessment of capture myopathy and muscular trauma. Additionally, the dry
      chemistry analyzer, typically used in clinics, reported significantly higher and
      less precise AST and ALT activities with poor correlation to those measured with
      wet chemical methods found in diagnostic laboratories. Therefore, these results
      cannot be clinically compared. Overall, the optimized wet chemical method was the
      most precise and diagnostically useful measurement of aminotransferase in
      samples. Additionally, there was a statistically significant difference between
      paired serum and plasma measurement, indicating that separate reference intervals
      should be established for serum and plasma. Finally, storage of these enzymes at 
      70 degrees C for 1 mo resulted in up to a 25% decrease in enzymatic activity in
      manatee plasma.

PMID- 18634209
TI  - Pharmacokinetics of orally administered phenylbutazone in African and Asian
      elephants (Loxodonta africana and Elephas maximus).
AB  - The pharmacokinetic parameters of phenylbutazone were determined in 18 elephants
      (Loxodonta africana and Elephas maximus) after single-dose oral administration of
      2, 3, and 4 mg/kg phenylbutazone, as well as multiple-dose administrations with a
      4-wk washout period between trials. After administration of 2 mg/kg
      phenylbutazone, mean serum concentrations peaked in approximately 7.5 hr at 4.3
      +/- 2.02 microg/ml and 9.7 hr at 7.1 +/- 2.36 microg/ml for African and Asian
      elephants, respectively, while 3 mg/kg dosages resulted in peak serum
      concentrations of 7.2 +/- 4.06 microg/ml in 8.4 hr and 12.1 +/- 3.13 microg/ml in
      14 hr. The harmonic mean half-life was long, ranging between 13 and 15 hr and 39
      and 45 hr for African and Asian elephants, respectively. There was evidence of
      enterohepatic cycling of phenylbutazone in Asian elephants. Significant
      differences (P < 0.0001) in pharmacokinetic values occurred between African and
      Asian elephants for clearance (27.9 and 7.6 ml/hr/kg, respectively), terminal
      half-life (15.0 and 38.7 hr, respectively), and mean residence time (22.5 and
      55.5 hr, respectively) using 2-mg/kg dosages as an example. This suggests that
      different treatment regimens for Asian and African elephants should be used.
      There were no apparent gender differences in these parameters for either elephant
      species.

PMID- 18634210
TI  - Development of a polymerase chain reaction test for Entamoeba invadens.
AB  - Entamoeba invadens is a protozoal parasite of reptiles that causes colitis,
      abscesses of liver and other organs, and sometimes acute death. It is generally
      considered a commensal of chelonians but has also been implicated as a cause of
      colitis, diarrhea, and death in gopher (Gopherus polyphemus) and leopard
      (Geochelone pardalis) tortoises. Diagnosis of E. invadens is currently by
      detection of trophozoites and/or cysts upon direct fecal examination. However,
      definitive diagnosis of E. invadens has been difficult due to the very similar
      morphology of nonpathogenic Entamoeba spp., including E. ranarum, E. insolita, E.
      barreti, and E. terrapinae. Definitive speciation of Entamoeba spp. is important
      to avoid misdiagnosis or overtreatment for nonpathogenic protozoa. It is also
      important for consideration of mixed species reptile collections to avoid
      exposing snakes and lizards to E. invadens. In this study, we developed
      polymerase chain reaction (PCR) primers for E. invadens, E. ranarum, E.
      terrapinae, and E. insolita and conducted PCR amplification of purified DNA from
      cell cultures, as well as purified DNA from reptile stool samples with E.
      invadens trophozoites added. As a result of this study, a naturally occurring
      infection of E. invadens was confirmed in a giant South American river turtle
      (Podocnemis expansa). This study has developed successful PCR primers for four
      species of Entamoeba and demonstrates that PCR is a promising diagnostic tool for
      the definitive identification of E. invadens.

PMID- 18634211
TI  - Relationship between separation time of plasma from heparinized whole blood on
      plasma biochemical analytes of loggerhead sea turtles (Caretta caretta).
AB  - Concentrations and activities of selected biochemicals of loggerhead sea turtles
      (Caretta caretta) were determined for plasma that was separated from whole blood
      samples that were kept up to 96 hr post collection (PC) in a refrigerator. Blood
      samples collected from seven juvenile captive loggerhead sea turtles were added
      to tubes containing lithium heparin and were placed on ice. Equal amounts of
      anticoagulated whole blood from the lithium heparin tubes were then aliquoted
      into plastic tubes and stored as whole blood under refrigeration until they were
      centrifuged at 0, 4, 24, 48, and 96 hr PC. Plasma was removed and the analytes
      that were measured were alkaline phosphatase (ALP), aspartate aminotransferase
      (AST), gamma glutamyl transferase (GGT), creatine kinase (CK), sodium, chloride,
      potassium, magnesium, calcium, phosphorus, cholesterol, glucose, urea nitrogen,
      uric acid, total protein, albumin, and globulin. Compared with values at 0 time,
      the only analyte to be significantly different at 24 hr PC was GGT (activity
      decreased by 25%). Compared with values at 0 time, significant differences at 96
      hr PC were only seen in AST (2% increase), GGT (25% decrease), glucose (7%
      decrease), and uric acid (25% increase). Although a statistically significant
      difference was found in concentrations of phosphorus and cholesterol over time by
      repeated measures analysis of variance (ANOVA), the follow-up multiple comparison
      procedure could not define the specific time points at which significant
      differences occurred. For all other analytes, significant differences over the
      time course of the study were not found. In these instances, the power of the
      ANOVA was sufficient (> or = 0.80) to detect any arithmetic differences of a
      clinically relevant magnitude. Although plasma should be separated from the
      cellular component of blood as soon as possible PC, in a field situation in which
      a centrifuge is unavailable, samples can be stored in a portable cooler up to 24
      hr without appreciable change in select biochemical analytes.

PMID- 18634212
TI  - Unidentified Plasmodium species in Australian black swans (Cygnus atratus)
      hatched and raised in North America.
AB  - A pair of Australian black swans (Cygnus atratus) with origins in Wakefield,
      Virginia, USA, was admitted to the quarantine area at the Baltimore Zoo for
      general health assessments before housing in the collections. During the
      quarantine period, no clinical signs of disease were manifest; however, upon
      examination of a blood smear, intraerythrocytic parasites were detected and
      initially determined to be Haemoproteus species. Diagnostic polymerase chain
      reaction (PCR) and sequencing results, however, indicated that the parasites were
      within the genus Plasmodium. Subclinical infections with Plasmodium species in
      birds may affect collection management, and transmission from refractory hosts to
      susceptible hosts should be considered when multispecies exhibits are used. In
      addition, changes in the dynamics of host-vector-parasite interactions might have
      significant impacts on wild or domesticated populations of birds.

PMID- 18634213
TI  - Fatal disseminated encephalitozoonosis in a captive, adult Goeldi's monkey
      (Callimico goeldii) and subsequent serosurvey of the exposed conspecifics.
AB  - A captive, adult male Goeldi's monkey (Callimico goeldii) (GM) presented in acute
      respiratory distress 4 yr after importation into the United States from Europe.
      Radiographs and echocardiogram were consistent with heart failure. The monkey
      died within 24 hr of presentation. Necropsy findings included multicentric
      arteritis and aortitis with aneurysm associated with microsporidian organisms
      morphologically consistent with Encephalitozoon species. Polymerase chain
      reaction confirmed organisms were Encephalitozoon cuniculi. Sequence analysis of
      amplicons generated by using primers specific for the polar tube protein of E.
      cuniculi determined the organism to be genotype II. An E. cuniculi serosurvey of
      potentially exposed conspecifics that represented approximately 40% of the
      captive GM population in the United States was conducted. Multiple individuals
      that had been imported from Europe with the individual of this report were
      seropositive via an immunofluorescent antibody assay for E. cuniculi. Multiple
      samples were available from 3 individuals that demonstrated a decrease in titer
      or reversion to seronegative status within 3 yr of initial positive status. All
      other GM were negative on serology. This case is unique in that the genotype
      identified (genotype II) was different than the genotype (genotype III) reported
      in other New World primate (NWP) species, the patterns of arteritis were
      different from the typical pattern of microsporidial vasculitis described in
      other species, and clinical disease was observed in an adult. Most reported cases
      of clinical disease secondary to E. cuniculi in NWP have been in neonates and
      juveniles.

PMID- 18634214
TI  - Diagnosis and treatment of Sarcocystis neurona in a captive harbor seal (Phoca
      vitulina).
AB  - A captive harbor seal (Phoca vitulina) presented with partial anorexia, ataxia,
      and head bobbing, which progressed to complete anorexia, lethargy, and persistent
      whole-body intention tremors within several days. Response to treatment with
      ponazuril, serology, and cerebrospinal fluid analysis supported a diagnosis of
      Sarcocystis neurona. Analysis of serum levels for ponazuril indicated that
      therapeutic levels could be achieved at a dosage of 5 mg/kg p.o. s.i.d., whereas
      clinical response was improved at a dosage of 10 mg/kg. Several months after
      initiation of antiprotozoal therapy, the neurologic signs resolved, although rare
      intermittent tremors were seen with significant exertion.

PMID- 18634215
TI  - Paresis in an Asian small clawed otter (Aonyx cinereus) associated with vertebral
      and ischial osteolysis caused by a malignant lymphangiosarcoma.
AB  - A 10-yr-old male intact Asian small clawed otter (Aonyx cinerus) was
      presumptively diagnosed by histopathology and immunohistochemistry with
      lymphangiosarcoma after bony destruction of the ischium and spinal column from
      local tumor invasion had caused progressive signs of hind limb lameness and
      paresis/paralysis, which led to humane euthanasia. At necropsy, the primary tumor
      was identified as a flocculent mass present under the caudal lumbar vertebrae.
      Multiple nerves were seen to run from the spinal cord into the wall of the mass.
      This mass had locally invaded the surrounding muscle, vertebral column, and
      spinal cord, which led to the clinical signs noted at presentation. Bony
      destruction was severe with almost complete obliteration of the right ischium and
      osteolysis of L6, exposing the spinal cord beneath. The tumor had metastasized to
      at least two different sites within the spleen. The abdominal tumor was confirmed
      to be of endothelial origin by the use of immunohistochemical staining for factor
      VIII-related antigen and was confirmed as lymphatic origin versus vascular origin
      because of the lack of red blood cells within the vessels. The length of time
      from initial presentation with hind limb lameness to euthanasia because of hind
      limb paralysis was 4 mo. This is the first report of lymphangiosarcoma, an
      uncommon malignant neoplasm of lymphatic origin, in a mustelid and the first
      report of neoplastic disease in an Asian small clawed otter. In addition, the
      presentation of hind limb paresis associated with bony lysis because of local
      tumor invasion has not been previously reported with lymphangiosarcoma in humans,
      domestic animals, or nondomestic animals.

PMID- 18634216
TI  - Multicentric squamous cell carcinona in a paca (Agouti paca) resembling Bowen's
      disease.
AB  - An 8-yr-old female paca (Agouti paca) was admitted at the Veterinary Hospital of
      the Belo Horizonte Zoo (Brazil) with an ulcerated cutaneous nodule of
      approximately 1.5 cm in diameter in the left ear. One week later, other cutaneous
      nodules were detected in various body locations. The animal died during a
      surgical procedure to remove the tumors. All cutaneous nodules were
      histologically similar with features of squamous cell carcinoma. Considering the
      predominant in situ nature of the lesion as well as its multicentric
      localization, the disease reported here closely resembles Bowen's disease, which
      has been described in humans and which has been identified as a rare neoplastic
      disease of cats, with one single report in a dog. This is the first report of a
      neoplastic disease in Agouti

PMID- 18634217
TI  - Nonsurgical repair of an umbilical hernia in two Asian elephant calves (Elephas
      maximus).
AB  - Umbilical hernias were diagnosed in two captive-born, female Asian elephant
      (Elephas maximus) calves several weeks after birth. Daily manual reduction of the
      hernias for 5 wk in the first case and for 5 mo in the second resulted in
      complete closure of the defects. Nonsurgical repair of uncomplicated, fully
      reducible umbilical hernias in Asian elephants can be an alternative to surgery.

PMID- 18634218
TI  - Carbon dioxide (CO2) laser treatment of cutaneous papillomas in a common snapping
      turtle, Chelydra serpentina.
AB  - Carbon dioxide (CO2) laser was used to treat multiple cutaneous papillomas on an
      adult female common snapping turtle, Chelydra serpentina serpentina. A
      combination of excisional and ablative techniques provided excellent
      intraoperative visibility and postoperative results due to the laser's unique
      ability to incise and vaporize soft tissue.

PMID- 18634219
TI  - Sarcoptic mange and Pelodera dermatitis in an American black bear (Ursus
      americanus).
AB  - An adult female free-ranging American black bear (Ursus americanus) was presented
      in poor body condition, with advanced skin disease. Skin changes included hair
      loss, lichenification, crusting, and focal erosions. Skin scrapings and
      histopathology identified two distinct parasitic conditions that were
      contributing to this animal's dermatitis. Large numbers of larvae, nymphs, and
      adults of Sarcoptes scabiei were present in the superficial epidermis, and
      nematodes consistent with Pelodera strongyloides were abundant within the hair
      follicles. This appears to be the first reported case of Pelodera dermatitis in a
      bear species, adding a new differential agent to the list for dermatitis in
      bears. The sarcoptic mange and poor body condition of this bear may have been
      contributing factors to the development of the opportunistic Pelodera
      infestation.

PMID- 18634220
TI  - Caesarian section and neonatal care in the aardvark (Orycteropus afer).
AB  - A 5-yr-old aardvark (Orycteropus afer) was presented with dystocia as a result of
      fetal oversize. A caesarian section was performed using the technique used in
      domestic dogs. Anesthesia was induced with medetomidine and ketamine and
      maintained with isoflurane. The neonate was initially unable to suckle because of
      swelling and paralysis of the face and tongue following the prolonged pressure of
      the dystocia. A Haberman feeder was used successfully from 5 days of age, and the
      calf suckled unassisted after 9 days, from which point it was parent-reared. Most
      captive aardvark calves have been hand-reared. Although all four of this female's
      calves have required some initial medical assistance, only the first was hand
      reared. A management strategy of overnight separation of the calves and dam has
      allowed the neonates sufficient rest and reduced injury and has reduced the need
      for hand-rearing.

PMID- 18634221
TI  - Serologic survey of woodchuck hepatitis virus in North Carolina woodchucks
      (Marmota monax).
AB  - The prevalence of woodchuck hepatitis virus (WHV) in wild populations of
      woodchucks is understudied and therefore unclear. Although infection is common in
      the southeastern region of Pennsylvania and surrounding states, it is virtually
      absent in New York and New England. Sera were collected from wild woodchucks from
      Orange County, North Carolina and tested for the presence of markers of current
      or previous infection with WHV. Of the 24 woodchucks tested, there were three
      animals (12.5%) with WHV surface antigen as well as antibodies to woodchuck
      hepatitis core antigen in their serum, indicative of active infection. There were
      four (17%) animals with antibodies to WHV core antigen but no woodchuck hepatitis
      surface antigen, indicative of prior infections. The remaining 17 animals had no
      detectable markers of WHV infection. These data indicate that WHV is present in
      central North Carolina at rates approaching those seen in endemic areas, such as
      the mid-Atlantic region of the United States.

PMID- 18634222
TI  - Oropharyngeal teratoma in a neonatal sable antelope (Hippotragus niger).
AB  - A neonatal male sable antelope (Hippotragus niger) was found dead. A 5 by 12-cm
      lobulated mass was present in the oral cavity, attached to the caudal border of
      the soft palate; this mass contained hair, cartilage, bone, nervous tissue,
      muscle, and multiple gland-like structures. Histopathologic diagnosis was
      consistent with oropharyngeal teratoma. As a result of the lack of wear of the
      fetal hooves, the firm, collapsed appearance of the lungs, and the lack of other
      gross or histopathologic abnormalities, the oropharyngeal tumor is suspected to
      have caused an airway obstruction, resulting in the calf's early postnatal death.
      This is the first report of an oropharyngeal teratoma in the veterinary
      literature.

PMID- 18634223
TI  - Thoracolumbar hemilaminectomy and spinal cord decompression in a lion-tailed
      macaque (Macaca silenus).
AB  - A 16-yr-old, castrated male lion-tailed macaque (Macaca silenus) presented with
      acute bilateral pelvic limb paralysis. Cisternal and lumbar myelograms
      demonstrated right-sided spinal cord compression at T13-L1. During an extradural
      hemilaminectomy, chronically ruptured disk material was removed at T13-L1, with
      moderate venous dilatation observed cranially. The macaque fully recovered from
      clinical signs within 2 mo.

PMID- 18634225
TI  - When medical care is futile.

PMID- 18634224
TI  - Secondary amyloidosis and renal failure in a captive California sea lion
      (Zalophus californianus).
AB  - A 16-yr-old, captive-born, female California sea lion (Zalophus californianus)
      was evaluated for intermittent lethargy, partial anorexia, and polydipsia of 2 wk
      duration. The animal was immobilized for physical examination. It was in thin
      body condition, with multifocal mucosal ulcerations over the caudal and ventral
      tongue. Blood was collected for hematology, serum chemistry, and leptospirosis
      serology. Serum chemistry revealed severe azotemia, mild hyperglycemia, and
      severe hyperphosphatemia. The animal went into cardiac arrest during recovery
      from anesthesia and died. On histopathology, abundant amorphous, finely
      fibrillar, eosinophilic material was deposited in the kidneys, and smaller
      amounts of the same material were found in the splenic and pancreatic vessels;
      these findings are consistent with systemic secondary amyloidosis. The animal
      also had chronic nephritis, which, coupled with renal amyloidosis, resulted in
      renal failure and death. Systemic amyloidosis should be considered as an
      additional differential diagnosis for renal failure in California sea lions.

PMID- 18634226
TI  - The one-person show.

PMID- 18634227
TI  - What your billing service says about you.

PMID- 18634228
TI  - Helping doctors who need help.

PMID- 18634229
TI  - The new doctor-patient paradigm.

PMID- 18634230
TI  - Trends in healthcare technology.

PMID- 18634231
TI  - What do you know about the history of nursing?

PMID- 18634232
TI  - Whether a registered nurse could face liability for rendering emergency aid.

PMID- 18634233
TI  - Bed bug re-emergence--what you should know.

PMID- 18634234
TI  - Lateral violence and bullying in the workplace.

PMID- 18634236
TI  - What condition could stem cells help first?

PMID- 18634235
TI  - Resiliency: a springy strategy for wellness.

PMID- 18634237
TI  - The obese should have to pay more for airline tickets.

PMID- 18634238
TI  - Having kids makes you happy.

PMID- 18634239
TI  - Give the girls a break.

PMID- 18634240
TI  - The fragile X factor.

PMID- 18634241
TI  - Fill up on flavor.

PMID- 18634242
TI  - [Caspases--a new target in inflammation and cancer therapy?].
AB  - The family of caspases - intracellular cysteine proteases - comprises enzymes
      engaged in inflammatory response or cell apoptosis. The activity of caspases is a
      determinant for the life span of many cells. Defects in activity of some members
      of the caspase family can be related to neurodegenerative disorders, autoimmune
      diseases and cancer. The current knowledge of the structure, substrate
      specificity and function of caspases encourages interfering with caspase
      signaling and to pharmacological manipulation of the cell apoptosis.

PMID- 18634243
TI  - [Concentration of IL-10, IL-13 and IFN-gamma cytokines in supernatants of
      microcultured CD4+ and NK cells in patients with non-allergic bronchial asthma].
AB  - THE AIM OF THIS STUDY was the evaluation of T lymphocytes and NK function in
      patients with non-allergic asthma. MATERIAL AND METHODS: Three groups: patients
      with non-allergic asthma (n = 30), patients with non-allergic asthma with
      concomitant recurrent infections (n = 24) and group of healthy adult volunteers
      (n = 20) were examined. CD4+ and NK cells were isolated from peripheral blood by
      magnetic separation method. Cells were cultured and level of cytokine IL-10, IL
      13, IFN-gamma in medium were measured. RESULTS: In patients with non-allergic
      asthma with recurrent infections mean value of IFN-gamma in medium from IL-15 +
      IL-12 stimulated NK cells was significantly lower compared with control group (p
      < 0.01). Mean value of IL-10 and IL-13 in medium from Con A stimulated CD4+ cells
      in patients with non-allergic asthma with recurrent infections were significantly
      higher than in control group (p < 0.05). CONCLUSIONS: Multitudes of cell and
      humoral factors interactions overlap dysfunction of immunological system in
      patients with non-allergic asthma. It causes higher susceptibility to infections
      factors especially viruses. Viruses give feedback for escalation of infection and
      worsening of clinical course of disease. Knowing mechanisms of inflammation
      intensification would let us specific prophylaxis use (specific antinflammatory
      or immunomodulatory drugs).

PMID- 18634244
TI  - [Estimation of selected parameters antioxidant barrier and lipid parameters in
      children with atherosclerosis risk factors].
AB  - Atherosclerosis is one of the most common causes of mortality in developed
      countries. One of the many factors in its etiopathogenesis are reactive oxygen
      species (ROS), excess of which comes from disturbances of enzymatic and
      nonenzymatic mechanisms of antioxidant barrier. THE AIM OF THIS STUDY was to
      estimate relations between the activity of chosen parameters antioxidant barrier
      and the lipid levels in children with atherosclerosis risk factors. MATERIAL AND
      METHODS: The study was carried out on 48 children with atherosclerosis risk
      factors. The control group consisted of 25 healthy children. Total cholesterol
      (TC), Triglycerides (TG), HDL-C, LDL-C were determined by enzymatic method. The
      activity of superoxide dismutase (SOD) was estimated by Misra and Fridivich's
      method, glutathione peroxidase (GSH-Px) with method proposed by Sedlak and
      Lindsay in modyfication Little and Brien and the activity o catalase (CAT) by
      Beer and Sizer's method. Malonyl dialdehyde (MDA) concentration was determined by
      Placer's method. RESULTS: Obesity, lipid disorders, and hypertension were the
      most frequent risk factors in the investigated children. Statistically
      significant higher concentration of TC, LDL-C, TG and lower HDL-C were observed
      in children with atherosclerosis risk factors. Activity of glutathion peroxidase
      was statistically significant higher in children with atherosclerosis risk
      factors (p < 0.001), activity of catalase was lower (p < 0.05). No significant
      differences in activity of superoxide dismutase and malonyl dialdehyde were
      observed in the investigated groups. CONCLUSION: Modificated activity of selected
      antioxidants in children with atherosclerosis risk factors could determine an
      index of antioxidant barrier and might potencially constitute the marker of early
      atherosclerotical risk development.

PMID- 18634245
TI  - [Silicosis and systemic lupus erythematosus--case report].
AB  - In the development of systemic lupus erythematosus (SLE) genetic predisposition
      are essential. The role of external factors such as viral infection, exposure to
      pesticide and silica dust and cigarette smoking are frequently emphasized in the
      development of this disease. On the basis of the observed case we decided to
      describe the problem of connection between silicosis and systemic lupus
      erythematosus (SLE).

PMID- 18634246
TI  - [Acute pancreatitis as a complication of diagnostic gastroduodenal endoscopy at
      10 years old girl--case report].
AB  - A 10-years old girl with chronic pancreatitis, in whom the symptoms of acute
      pancreatitis appeared after gastroduodenal endoscopy is described. One hour after
      endoscopy the following symptoms appeared: unigastric and epigastric pain,
      intense vomiting, elevated amylase activity in the serum (2744 micro/l) and in
      urine (23738 micro/l) as well as serum lipase activity (4350 micro/l). Ultrasound
      of the abdomen revealed the enlargement of the pancreas with hypodense structure
      in comparison to the examination conducted couple hours earlier, and trace of
      fluid around the pancreas. In the treatment intravenous omeprazole, a strict diet
      and intravenous fluid and electrolytes were administered. After two days vomiting
      and abdominal pain subsided, biochemical results improved and the reduction of
      pancreas dimensions in ultrasound study was observed.

PMID- 18634247
TI  - [Twenty-two months old girl with haemorrhagic gastritis as a complication after
      the nonsteroid anti-inflammatory drugs application--case report].
AB  - The aim of case report was to pay attention for possibility of side effects of
      nonsteroid anti-inflammatory drugs. Child of young and healthy parents was born
      after normal pregnancy, natural delivery. The disease started in two days before
      the admission, child had fever, cough and sneezing. Mother gave her two doses of
      ibuprofen. On the time of admission general state of patient was moderate; girl
      was apathic. In physical examination features of upper respiratory tract
      infection were shown. In the course of treatment antibiotic and symptomatic drugs
      including paracetamol (3x5 ml) were delivered. During the second day of treatment
      child had no appetite, started to vomit with fresh and haemolized blood.
      Parenteral hydratation was started. Emergency gastroscopy was done and features
      of haemorrhagic gastritis were shown. Anti-inflammatory drugs were no more used
      and delivery of omeprazole was started. Parenteral hydratation was continued.
      General state of patient was better. In the sixth day after bleeding child was
      excripted in good general state with order of use of omeprazole. Parents were
      informed about the restriction of anti-inflammatory drugs use. The aim of case
      report was to pay attention that haemorrhagic gastritis may be one of side
      effects of nonsteroid anti-inflammatory drugs used accordingly to actual
      standards.

PMID- 18634248
TI  - [Intranasal meningocele presenting as a nasal polyp--case report].
AB  - Intranasal meningocele occurs rarely. It is difficult to diagnose because its
      appearance resembles common polyps. If it coexists with other inborn cranio
      facial malformation they are easier to diagnose. In the case investigated by us,
      the 32 year-old woman's ailments suggested intranasal polyps and we discovered
      the meningocele localized intranasal on the right. The CT scan of the nasal
      sinuses is the most reliable examination for the developing diagnosis. The CT
      findings revealed the meningocele protruding from the anterior cranial fosse
      through the lamina cribrosa to the right nasal cavity. During the operation the
      meningocele was removed and the durra mater was sutured. The bony-mucosal lesion
      was covered with composite graft taken from bony part of nasal septum and mucosal
      part of the inferior turbinate. The graft has been incorporated into the
      surrounding tissue. Neither a cerebrospinal fluid leak nor any other
      complications have been reported within the past 6 years. Therefore, we consider
      this a successful procedure.

PMID- 18634249
TI  - [Primary central nervous system lymphoma with initial symptoms suggesting herpes
      encephalitis].
AB  - Primary central nervous system lymphoma (PCNSL) is rare neoplasm, affecting both
      immunocompetent and immunodeficient patients. It is usually seen as intracranial
      tumor, but it can often involve cerebrospinal meninges, eyeballs and spinal cord.
      Although PCNSL is sensitive both to radiotheraphy and chemotheraphy, it's
      recurrences are very frequent. Mean survival time does not exceed several months.
      We described a case of 43 year old patient with diagnosed PCNSL and discussed
      clinical signs, diagnostics and treatment of the neoplasm. In our case report we
      emphasized transient remission after treatment with corticosteroids, which
      delayed a correct diagnosis and worsened final prognosis.

PMID- 18634250
TI  - [Pyoderma gangrenosum--an interdisciplinary diagnostic problem].
AB  - Pyoderma gangrenosum is a rare, chronic, progressive and noninfectious necrosis
      of skin with an unclear etiology. It usually coexists with the systemic
      disorders. Clinically it appears as a rapidly spreading ulceration in a various
      location. Pyoderma gangrenosum often starts as pustule, nodule or local
      inflammation which suggest the diagnosis of bacterial infection of skin such as
      furuncle or phlegmon so patients with early symptoms could be refered to surgical
      units. We presented the case of pyoderma gangrenosum which affected a 47-year-old
      woman. Due to the presumptive diagnosis of phlegmon of the patient's right arm
      she was initially admitted to surgical ward. Sometimes there are many
      difficulties with an early diagnosis of pyoderma gangrenosum because of its
      rarity, distinctness of clinical pictures, lack of characteristic histology and
      laboratory tests. We would like to emphasize that pyoderma gangrenosum should be
      always included to the differential diagnosis of a rapidly progressing ulceration
      of skin especially if there is no response to standard therapy.

PMID- 18634251
TI  - [Acute amnesic syndrome--patient's disorientation baffles a doctor].
AB  - We report a 53-year-old female patient who presented a sudden dramatic memory
      disorder following coronary and cerebral angiography. The patient was disoriented
      and kept repeating the same questions about time and place. Transient global
      amnesia was ultimately diagnosed using the Hodges and Warlow criteria. We briefly
      discuss how to distinguish transient global amnesia from psychogenic amnesia,
      transient epileptic amnesia and transient ischemic attack.

PMID- 18634252
TI  - [Hypoxemia in pulmonary embolism--the occurrence, patomechanism and
      significance].
AB  - Blood gas analysis is often performed in the initial diagnosis of acute pulmonary
      embolism (APE), and it is recognized that hypoxemia (H) strengthen its suspicion.
      However, the diagnostic power of hypoxemia is very week. Hypoxemia, usually deep,
      occurs in almost all patients with massive APE whereas moderate hypoxemia occurs
      in about 75% of unselected normotensive APE population without co-morbitides. H
      occurs also in most patients with chronic thromboembolic pulmonary hypertension
      (CTEPH). The patomechanism of H in pulmonary embolism is not completely known and
      is associated mainly with obstruction of pulmonary vasculature, pulmonary
      hypertension, and with co-morbitides. However, the secondary failure of
      ventilation followed by alveolar hypoxia can not be excluded in many cases of
      chronic pulmonary embolism. Hypoxemia seems to have moderate value in prognosis
      in APE and in CTEPH. H in massive APE requires oxygen therapy, and it can be
      speculated, whether long term oxygenation should be added to the anticoagulation
      in nonoperated, hypoxemic patients with CTEPH.

PMID- 18634253
TI  - [The relationships between aging and disease in the elderly asthma].
AB  - In developed countries, the population aged 65 and over has been increasing.
      Asthma is a common disease among older persons and it may appear de novo above
      the age of 65. The prevalence of the disease in elderly people is estimated to be
      between 6.5% and 17%. Available data about older asthma patients are limited by a
      small numbers of studies reports. Asthma beginning late during the lifetime seems
      to be more severe, but the natural history of this disease appears to be
      variable. The characteristics of asthma in older patients is being complicated by
      the changes related to aging. Aging of the respiratory system is a natural
      process associated with its structural and functional changes. These changes may
      influence the expression of asthma. Differentiating physiological ageing from
      pathological changes related to disease can be difficult. Interactions of some of
      these mechanisms in asthma in the elderly are analyzed in this article.

PMID- 18634254
TI  - [Stress related mucosal disease prophylaxis in intensive care unit patients].
AB  - Among the patients admitted to the Intensive Care Unit there frequently occur
      disturbances of the upper gastrointestinal tract. They can be found as stress
      ulcerations which in turn may lead to bleeding. The high incidence of stress
      ulcers and bleedings from the upper gastrointestinal tract is associated with
      disturbances of gastric acid secretion, an interrupted integrity of gastric
      mucosa and abnormal motor activity of gastrointestinal tract. The presence of
      clinically important bleeding results in prolonged hospitalization and increased
      mortality. The aim of this study is twofold; first, the pathogenesis and the
      consequences of stress-related mucosal disease are elucidated. Afterwards, the
      prophylaxis modalities are presented on the basis of the latest medical
      literature.

PMID- 18634255
TI  - [Novel aspects of pathogenesis of hereditary hemochromatosis].
AB  - Patients with hereditary hemochromatosis (HC) may present a plenty of clinical
      symptoms, thus are referred to various specialists and may prone a significant
      diagnostic dillema. The molecular basis of hemochromatosis is more complex than
      expected. In 1996 HFE gene was identified and its main mutations (C282Y and H63D)
      were described as well as their high frequency in population of European descent.
      Them: Most patients with clinical symptoms of hemochromatosis are homozygous for
      C282Y but it is also clear that some families are linked to rarer conditions,
      named "non-HFE hemochromatosis". Between 2000-2004 other genes involved in iron
      homeostasis were intensively studied, leading to recognition of hepcidin (HAMP) -
      the most important iron hormone, hemojuvelin (HJV), transferin receptor 2 (TfR2)
      and ferroportin. Recent findings led to novel hypothesis on potential digenic
      modes of inheritance or the involvement of modifier genes. Hepcidin plays a
      central role in mobilization of iron, HFE, TfR2 and HJV playing a modulating role
      in its production, related to the body's iron status. It has also been
      demonstrated that HAMP negatively regulates cellular iron efflux by affecting the
      ferroportin cell surface availability. The result of such a wide investigations
      is OMIM classification of hereditaty hemochromatosis, typing four types of the
      disease.

PMID- 18634256
TI  - [Advances in the treatment of acromegaly].
AB  - Acromegaly is a slow developing chronic debilitating disease caused by a growth
      hormone (GH)-producing pituitary adenoma. The clinical consequences of acromegaly
      result both from excess GH secretion and from mass effect of the pituitary
      tumour. The disease is associated with increased morbidity and mortality compared
      to normal population. Currently available therapies for acromegaly are
      transsphenoidal surgery, radiotherapy and medical therapy. The last includes
      dopamine agonists, slow release formulation of somatostatin analogues and
      pegvisomant, a GH-receptor antagonist. All these forms of treatment attempt to
      control the disease by reducing GH secretion from the tumour and inhibiting the
      growth of adenoma. The decision concerning the choice of therapy should depend on
      age, the severity of acromegaly and the presence of its complications and should
      also consider the dangers associated with each treatment. This review paper
      summarizes the contemporary treatment of acromegaly with special emphasis on
      their established benefits and risks.

PMID- 18634257
TI  - [Current views on the role of dehydroepiandrosterone in physiology, pathology and
      therapy].
AB  - Dehydroepiandrosterone (DHEA) and its sulfate metabolite (DHEAS) are the major
      androgens secreted by the human adrenal gland. The decline in their production is
      the most characteristic age-related change in the adrenal cortex. This process,
      known as 'adrenopause' may contribute to the increased incidence of
      atherosclerosis, cancer, or dementia in older people. The possibility of using
      DHEA in management has attracted considerable attention over recent years.
      Whereas DHEA therapy seems to be effective in treating patients with adrenal
      insufficiency and systemic lupus erythematosus, clinical studies investigating
      the potential efficacy of DHEA therapy in multiple other disorders (Alzheimer
      disease, depression, cardiovascular disease, osteoporosis, sexual dysfunctions)
      have not provided consistent results. Further research is also needed to better
      assess the efficacy and safety of DHEA supplementation in patients with advanced
      age. This review evaluates current understanding of physiology and pathology of
      DHEA production and summarizes the possible therapeutic value of this hormone.

PMID- 18634258
TI  - [Calcium ions, glutaminate acid, hypothalamic-pituitary-adrenal axis, calcium
      dependent ATP-ase as causes of oxidative damage in depression patients (part
      II)].
AB  - Depressive disorder is still a rising and important problem in the modern world,
      it affects about 15% of the population. Present forms of treatment are effective
      in about 70% and require monthly therapy which sometimes causes side effects.
      Last decade studies paid attention to theories different to monoaminergic and to
      neurodegenerative changes mainly in the limbic system of hippocampus. In this
      article authors show a relationship between calcium ions, glutaminergic
      transduction and disfunction of hypothalamic-pituitary-adrenal (HPA) axis. They
      also take into account the activity of calcium dependent ATPase and its influence
      on overproduction of reactive oxygen species in the central neuron system (CNS).
      In the second part authors conclude that deregulation of calcium ions
      concentration in and out of cells and decreased activity of calcium dependent
      ATPase stimulate tricarboxylic acid cycle, oxidative phosphorilation.
      Mitochondria work faster and consume more oxygen. It correlates well with
      overproduction of reactive oxygen species (RFT). Above process results in neurons
      apoptosis and necrosis.

PMID- 18634259
TI  - [Pathogenesis, diagnosis and treatment of osteoporosis in men].
AB  - Osteoporosis traditionally is connected with women health, although recently has
      received increasing attention as one of the most important disorders in men.
      Lifetime risk of any fragility fracture in men has been estimated to 15-25%
      compared with about 50% in women. Less than one third of all nonvertebral
      fractures and about 15% vertebral fractures occur in men. However mortality
      connected with hip fractures in men is approximately 3-hold higher than in women.
      The principles factors that are necessary to obtain and maintain proper bone
      mineral density in men, besides genetic factors, are sex hormone - testosterone
      and also estrogens. The rarely occurrence of male osteoporosis is associated with
      increased peak bone mass and bone strength mainly due to periosteal expansion,
      and also with lack of phase of accelerated bone loss. Currently
      aminobisphosphonate (alendronate) and recombined human parathormone (rhPTH) has
      been proved to reduced fracture risk in men. In men with osteoporosis and late
      onset hypogonadism (LOH) increasing of bone mineral density after testosterone
      replacement therapy was observed, but influence of this treatment on fracture
      risk is still unknown. As a general rule, men with osteoporosis should receive
      adequate calcium (1200-1500 mg/day) and vitamin D/alfacalcidol supplementation,

PMID- 18634260
TI  - [Role of matrix metalloproteinases in primary systemic vasculitis].
AB  - Primary systemic vasculitis comprise a group of diseases such as Wegener's
      granulomatosis, Kawasaki disease, Takayasu arteritis, giant cell arteritis with
      various clinical manifestations, and an etiology not fully understood. The
      pathogenesis involves an inflammatory infiltration of the vessel wall, which
      results in its damage. Matrix metalloproteinases seem to participate not only in
      the degradation of structural components of a vessel wall which leads to bleeding
      and/or aneurysmal dilatation. In addition, they play a significant role in the in
      inflammatory cells migration and development of inflammatory infiltration. This
      process, and the proliferation and migration of smooth muscle cells may result in
      the narrowing of the affected vessels. This article outlines the role of matrix
      metalloproteinases in primary systemic vasculitis.

PMID- 18634261
TI  - [Value and circadian variations of QT dispersion in patients with diabetes
      mellitus and coronary artery disease].
AB  - The frequency of onset of acute coronary syndromes and sudden cardiac death has
      been reported to have circadian variations, with a peak incidence in early
      morning hours. It has also been known that acute ischemia is a potent stimulus to
      increased dispersion of repolarization and development of malignant arrhythmias.
      QT dispersion (QTd) is used as an index of heterogenity of the ventricular
      repolarization and increases in patients with ischemic heart disease. The aim of
      the study was to investigate diurnal variations of QTd in patient with triple
      vessel coronary artery disease (CAD) with and without diabetes mellitus type 2
      (DM). MATERIAL AND METHODS: We investigated of 28 patients with stable triple
      vessel CAD and 32 patients with similar advancement of changes in coronary
      circulation with co-existing DM. We excluded patients with prior myocardial
      infarction, taking oral medications which might alter QT interval and patients in
      which measurements of QT were difficult to perform or impossible. QTd
      measurements were taken semi-automatically every hour from 24 hours 12 leads
      Holter monitoring system (SUPRIMA 12). Measurements were verified independently
      by three observers. RESULTS: CAD patients without DM had QTd significantly
      greater in the morning hours (6 a.m. to 9 a.m.) in comparison with the other
      times (p < 0.01). The shortest QTd was measured during the night between 10 p.m.
      and 1 a.m. We did not observed circadian variations of QTd in patients with co
      existent DM and values of QTd in this group was significantly greater then in CAD
      without DM group (p < 0.001). CONCLUSIONS: Our data proved that QTd in patients
      with CAD had a circadian variation with a peak value in the morning hours shortly
      after awakening. Patients with DM and CAD had not circadian variation of QTd but
      QTd values, during whole day and night, were significantly greater then patients
      without DM.

PMID- 18634262
TI  - [The assessment of nitric oxide metabolites in gastric juice in Helicobacter
      pylori infected subjects in compliance with grade of inflammatory lesions in
      gastric mucosa].
AB  - The infection of H. pylori causes inflammatory lesions in gastric mucosa--until
      atrophic gastritis, intestinal metaplasia, dysplasia (precancerous states) and
      finally to gastric cancer or lymphoma. The mechanism of mentioned disturbances is
      complicated, no doubt that nitric oxide plays here very important role. It is
      proved, that H. pylori causes essential oxygen metabolism disturbances by
      activation of inflammatory infiltration's cells to oxide reactive forms as nitric
      oxide formation. Nitric oxide as oxide radical could react with other free
      radicals and contribute to oxidative lesions of gastric mucosa and alterations of
      its structure. The aim of the study was try to answer the question: 1. Is this
      the relationship between NO metabolites concentrations in gastric juice and
      morphological state of gastric mucosa? 2. Does H. pylori eradication influence on
      NO metabolites concentrations in gastric juice? 3. Does H. pylori eradication
      influence on grade of inflammatory lesions in gastric mucosa? MATERIAL AND
      METHODS: The study included 75 subjects between of 21 to 60 years, infected with
      H. pylori with diagnosed (according to the Sydney system) different stages of
      chronic gastritis progression. The type of inflammation, activity, the presence
      of atrophy, intestinal metaplasia and H. pylori infection were assessed. The
      study group was divided into 3 subgroups: group I--25 subjects with chronic
      active gastritis, group II--25 subjects with chronic atrophic gastritis without
      intestinal metaplasia, group III--25 subjects with chronic atrophic gastritis
      with intestinal metaplasia. Control group comprised 20 healthy subjects, without
      H. pylori infection. In each patient during gastroscopy 5 biopsy specimens for
      histopathologic examination and for urea test and 3 ml gastric juice were
      collected. The concentration of nitric oxide metabolites in gastric juice was
      determined with spectrophotometric method, based on Griess reaction. H. pylori
      infection was detected using fast urea test (CLO--test), confirmed by
      histopathological examination (stained Giemsa method) and non-invasive urea
      breath test (UBT-13C). In H. pylori--infected patients the above mentioned
      investigations were performed three times -before, in 8 weeks and in 12 months
      after antibacterial treatment's finish. In antibacterial therapy we use 7-days
      three-drugs therapy (omeprasole, amoksycillin and clarythromycin). RESULTS: The
      concentration of nitric oxide metabolites in gastric juice in healthy subjects
      was 6.81 +/- 2.23 micromol. In patients with chronic gastritis, H. pylori
      infected was significantly higher--in patients with chronic active gastritis was
      9.29 +/- 2.19 micromol/l, in patients with chronic atrophic gastritis--10.25 +/-
      2.31 micromol/l (p < 0.01), in patients with intestinal metaplasia--11.89 +/-
      2.46 micromol/l (p < 0.01). 8 weeks after antibacterial treatment's finish the
      concentration of nitric oxide metabolites in gastric juice in each group
      decreased and were: in patients with chronic active gastritis was 8.18 +/- 1.63
      micromol/l, in patients with chronic atrophic gastritis--10.02 +/- 2.28
      micromol/l, in patients with intestinal metaplasia--10.83 +/- 2.32 micromol/l.
      The differences were not statistically significant. 12 months after antibacterial
      treatment's finish the concentration of nitric oxide metabolites in gastric juice
      in each group decreased and were: in patients with chronic active gastritis was
      6.90 +/- 1.43 micromol/l, in patients with chronic atrophic gastritis--7.22 +/-
      2.01 micromol/l, in patients with intestinal metaplasia--7.56 +/- 1.98
      micromol/l. The differences were statistically significant--p < 0.05, p < 0.01. 8
      weeks after antibacterial treatment's finish in each patient also the gastroscopy
      was performed and another biopsy specimen for histopathologic examination were
      collected. Only in group I in microscopic image the decreased of inflammation
      intensity was find (both in antrum and in corpus)--however the differences were
      not statistically significant. In the other groups the alterations in gastric
      mucosa do not improve significantly. The gastroscopy was performed again in 12
      months after antibacterial treatment's finish. In group I the significant
      decrease or regression of inflammatory infiltration (in corpus and in antrum) was
      found. Also in group II the significant decrease of the grade of atrophy and
      similarly in III group the improvement of histopathological state were observed.
      CONCLUSIONS: 1. The increase of NO metabolites concentration demonstrates
      positive correlation with grade of inflammatory lesions in gastric mucosa. 2. The
      effective antibacterial therapy causes the decrease of NO metabolites
      concentration in gastric juice, especially in patients with chronic active
      gastritis. 3. Eradication influence on decrease of grade of lesions' progression
      in gastric mucosa just in 12 months after effective antibacterial therapy.

PMID- 18634263
TI  - [Causes and consequences of frequent hospitalization among schizophrenic
      patients].
AB  - Schizophrenia is one of the most frequent mental diseases. The probability of
      being taken ill with this psychosis among the whole population is 1%. Frequent
      hospitalizations of schizophrenic patients prevent them from normal and effective
      functioning in a society. AIM OF THE STUDY: Conducted research had an aim to
      isolate and define the risk factors of rehospitalization among schizophrenic
      patients. MATERIAL AND METHODS: In the research, the authors used their own
      questionnaire which provided the demographic, social and medical data. The
      research was based on archival case histories of schizophrenic people who were
      the patients of a mental hospital. The research was conducted among 65 people (27
      women, 38 men) who were hospitalized more than 15 times in the schizophrenic
      treatment. RESULTS: Psychiatric rehospitalizations in schizophrenia are
      conditioned not only by medical factors connected with the disease itself, but
      also by demographic and social factors. CONCLUSIONS: 1. The decisive role in
      rehospitalization of schizophrenia patients plays a small availability of
      alternative psychiatric care in the patients' dwelling place as well as the lack
      of regularity in the continuation on treatment after leaving the mental hospital.
      2. Patients' family status, relationship with family and friends and the level of
      acceptance and understanding of their disease decline the risk of
      rehospitalization. 3. The greatest risk of rehospitalization is among people from
      the lowest class--lonely, young men with primary or vocational secondary
      education, having no permanent employment.

PMID- 18634264
TI  - [Influence of low magnetic field on lipid peroxidation].
AB  - Free radicals (FR) are atoms, molecules or their fragments, whose excess leads to
      the development of the oxidizing stress, which is the cause of many neoplasmic,
      neurodegenerative, inflammatory diseases and aging the organism. The main
      exogenous sources of free radicals are among others: industrial pollution,
      tobacco smoke, ionizing radiation, ultrasound and magnetic field. The low
      frequency magnetic field is more and more applied in the physician therapy. The
      aim of our study was to prove, if the magnetically field applied in the
      magntetotherapy, affects generating the reactive forms of oxygen according to its
      working time. MATERIALS AND METHODS: The research material made up male, adult,
      Sprague-Dawley race rats age 3-4 months. To investigation compounds reacting with
      the tiobarbituric acid, the blood was taken from the rat caudal vein into the
      test-glass including EDTA before being affected by the magnetic field. After the
      single exposition and after 14 days of being affected by the magnetic field, the
      concentration of the compounds reacting with the tiobarbituric acid in the serum
      was measured. RESULTS: After the single exposition to the changeable magnetic
      field (frequency 40 Hz, induction 7 mT, working time 30' and 60 min) the process
      of the peroxidation of lipids slowed down. A increase of the peroxidation of
      lipids was observed after 14 days and these changes are statistically
      significant. CONCLUSION: Low magnetic field used in magnetotherapy causes the
      changes of the generating the reactive forms of oxygen.

PMID- 18634265
TI  - [Sleep disturbances and their effect on the sustained attention in patients with
      Parkinson's disease].
AB  - Aim of the study was to compare prevalence of sleep disturbances in patients with
      Parkinson's disease (PD) and in subjects with ischaemic stroke of the right
      cerebral hemispher and to estimate an effect of daytime sleepiness on sustained
      attention in patients with PD. MATERIAL AND METHODS: Forty eight patients with PD
      were included. The mean age was 65.9 (44-80) years, mean disease duration and
      mean Hoehn and Yahr Staging Scale were 6.6 (0.8-18) years and 2.5 (1.0-4.0),
      respectively. Control group consists of forty seven patients (mean age 66.2
      years) with ischaemic stroke of the right cerebral hemisphere, without any
      language problems (mean Rankin Scale: 2.0). Both, PD and control patients were
      evaluated with: Parkinson's Disease Sleep Scale (PDSS), Epworth Sleepiness Scale
      (ESS) and Beck Depression Inventory (BDI). PD patients were also assessed with
      Visual Continuous Attention Test (DAUF). RESULTS: PD patients obtained
      significantly lower (p < 0.05) scores on PDSS and significantly higher (p < 0.01)
      scores on ESS than patients with stroke. There were no significant differences
      within PD and control subjects on BDI. On the basis of ESS results PD patients
      were divided into two subgroups: PD1--patients with daytime sleepiness (ESS score
      > 10.0) and PD2--patients without daytime sleepiness. PD1 patients obtained
      significantly worse scores than PD2 ones on DAUF (significantly decreased number
      of correct reactions: p < 0.05 and significantly increased number of incorrect
      reactions: p < 0.05). CONCLUSIONS: Nighttime sleep disturbances and daytime
      sleepiness are more pronounced in PD patients than in subjects with ischaemic
      stroke of the right cerebral hemisphere. PD subjects with daytime sleepiness show
      disturbances in the sustained attention.

PMID- 18634266
TI  - [Nonspecific colon ulcer--case report].
AB  - Nonspecific colon ulcer (NSCU) was described by Crulveilhier in 1832, but strict
      definition, occurrence rates and diagnostic and therapeutic guidelines have not
      been yet established. AIM: to present a case of a rare disease of the colon with
      discussion on diagnostic and therapeutic principles. CASE REPORT: A 28-year-old
      female diagnosed for constipation and flatulence underwent endoscopy and a
      descending colon lumen stenosis, measuring about 1.0 cm in length, with some
      mucosal erosions, was found. On the basis of the performed diagnostics,
      unspecific nature of the disease was determined and conservative treatment with
      endoscopic follow-up was initiated. In a follow-up examination, performed 2
      months later, spontaneous ulceration healing was revealed with a scar replacing
      the abovementioned lesion. DISCUSSION: Clinical symptoms depend on disease
      dynamics and lesion location. Diagnosis is based on exclusion of known vascular,
      infective, unspecific inflammatory and traumatic causes. Therapy of uncomplicated
      causes is based on conservative treatment with endoscopic follow-up. CONCLUSIONS:
      The disease does not cause any specific clinical symptoms and often mimics other
      abdominal diseases. Diagnosis is based on exclusion of known causes. Therapy of
      most uncomplicated cases comprises conservative therapy and endoscopic follow-up.

PMID- 18634267
TI  - [Endosonography and endoscopic submucosal dissection in rectal cancer--case
      report].
AB  - This paper presents a case report of a 61 year-old man who had diagnosed in
      colonoscopy rectal cancer of early stage. In endosonography (EUS) intramucosal
      lesion without enlargement of regional lymph nodes was demonstrated. The patient
      was qualified for endoscopic therapy by submucosal dissection (ESD). The
      treatment was performed without any complications. The histological findings
      confirmed an early stage of rectal cancer--This, according to TNM classification.

PMID- 18634268
TI  - [Fructose-1,6-bisphosphatase--marker of damage to proximal renal tubules].
AB  - Pathological processes disturbing function of renal proximal tubules, increase
      activity of fructose-1,6-bisphosphatase (FBP-1) in urine. FBP-1 is cytosolic
      enzyme which occured mainly in cells of proximal renal tubules, and to small
      extent in cells of pars recta. After damage to the cell membrane FBP-1 is more
      rapidly excreted to the urine, than enzymes residing in other cell organelles.
      Fructose-1,6-bisphosphatase was isolated from rabbit muscle in 1943 by Gomori,
      and from spinach in 1958 by Racker i Schroder. Highest activity of FBP-1 was
      found in liver and kidneys, lesser in ileum, leucocytes, muscles and brain.
      Fructose-1,6-bisphosphatase is one of four key enzymes of gluconeogenesis
      performing synthesis of glucose from non sugar substrates. FBP-1 catalyses
      hydrolysis of fructose-1,6-bisphosphate in cytoplasm of the cell. There are many
      reports on properties and significance of FBP-1 in plant and animal tissues, but
      only few reports on activity of this enzyme in urine. Reason for little interest
      in determination of FBP-1 activity in urine, is relative instability of this
      enzyme in urine.

PMID- 18634269
TI  - [Effects of ethanol on hemostasis].
AB  - Ethanol has multiple effects on hemostasis, affecting platelets, coagulation
      factors, and the fibrinolytic system. Results in the literature growing evidence
      is pointing to the following effects of ethanol or its metabolites: partial
      platelet activation generating poorly functioning platelets, decreased levels of
      fibrinogen and selected other factors, and increased fibrinolysis. This
      beneficial effect on hemostasis is likely to contribute to the protective effect
      of cardiovascular diseases.

PMID- 18634270
TI  - [Endoscopic ultrasonography in the assessment and management of complications of
      liver cirrhosis].
AB  - Upper gastrointestinal endoscopy plays a major role in the diagnostic and
      treatment of the complications of portal hypertension in patients with liver
      cirrhosis. Endosonography (EUS), which combines routine endoscopy and ultrasound
      examination has been so far infrequently used in these cohort of patients despite
      the fact that it offers much more detailed analysis of several features of portal
      hypertension, not detected with routine endoscopy. These include detection of so
      called "deep varices", assessment of the thickness of gastric wall,
      differentiation between thickened folds and varices or detection of subclinical
      amounts of ascitic fluid. In this paper we systematically review the current and
      potential future applications of EUS in the diagnostic and treatment of patients
      with liver cirrhosis.

PMID- 18634271
TI  - [Anesthesia for fetal therapy on the eve of 21st century--possibilities, hazards
      and perspectives].
AB  - Fetal therapy is a new branch of medicine, developing quickly now, that deals
      with diseases and congenital anomalies diagnosing and therapy in an unborn child-
      in utero. Nowadays, fetus has become a fully-privileged patient for medical and
      surgical therapies. The aim of the review is to present the possibilities of
      anesthesia for fetal therapy now at hand, to delineate general tendencies of
      further development and to highlight dangers and controversies. Fetal therapy is
      a fascinating and dynamically developing field of medicine which has practically
      gone beyond the limits of a medical experiment. Methods utilised are accepted,
      although still raise numerous controversies of medical and ethical nature.
      However, progress in perinatology, medical technique and pharmacology and in
      study on human genome raise optimism and allow to believe that in close future
      fetal therapy will be broadly accepted as a routine therapeutic method.

PMID- 18634272
TI  - [The role of anaerobic bacteria in peritonsillar abscesses].
AB  - Peritonsillar abscess (quinsy) is a complication of acute bacterial tonsillitis.
      Its treatment remains controversial. Needle drainage of the abscess may provide
      an alternative to incision or tonsillectomy. An important element of controversy
      is the choice of antibiotics after surgical drainage of the abscess. Results of
      many studies support the resistance of grown bacteria to many antibiotics and the
      potential importance of anaerobic bacteria in development of peritonsillar
      abscesses. Although bacteria grown from the pus vary among the continents,
      clinical implications resulting from the microbiological studies are similar.
      Patients with peritonsillar abscesses should be treated with antibiotics
      effective against both aerobic and anaerobic bacteria. In the routine management
      of peritonsillar abscess, bacteriologic studies are unnecessary on initial
      presentation. It is, however, necessary to consider infection with anaerobes.
      Therefore, penicillin and metronidazole are recommended as the antibiotic regimen
      of choice in the treatment of peritonsillar abscesses. If this treatment is
      ineffective, broad-spectrum antibiotics (clindamycin) should be administered.

PMID- 18634273
TI  - [Epuli--the inflammatory or neoplastic tumor].
AB  - Epuli (granulomas) are the most frequently observed gingival tumours. The
      etiopathogenesis of the hyperplasia is not yet clear, and classification
      inconsistent. Literature on the subject presents considerable discrepancies
      regarding the tumours origin. The factors determining their development, growth
      rate, and tendency to recur are still unknown although several options have been
      considered, i.e., type of injury or inflammatory process, hygiene, nutrition,
      alcohol, nicotine, pharmacotherapy, hormonal status, and immune efficiency. The
      opinions of authors of the literature on etiopathogenetic, the classification,
      the clinical images and the treatment of epulides are represented.

PMID- 18634274
TI  - [Derivatives pyrazoles used in a medical treatment].
AB  - Contemporary coordinative chemistry is still searching new substances that might
      constitute good ligands for transient metal ions: Cu(II), Ni(II), Co(II), Pt(II),
      Pd(II) oraz Cr(III). Pyrazole and its derivatives are able to make complexes with
      transient metal ions. There is a connection between pharmacological and chemical
      structure among pyrazole derivatives used in a medical treatment. A chemical
      division is coincident with a pharmacological division. Pyrazole-5 derivatives
      are mainly analgesic, antipyretic and less anti-inflammatory and diastolic but
      pyrazolidyn-3.5-dion derivatives are anti-inflammatory. The main part of non
      steroid anti-inflammatory drugs belonging to pyrazolone derivates has a phenyl
      group at the first position. The activity and toxicity of this drugs are
      dependent on groups being at the fourth position. For example, the dimethylamino
      group makes aminophenazon antianalgetic, and yet is also responsible for a big
      toxicity. Azole derivatives are antimycotic and are ingredients of some ointments
      and creams. Chemical groups at the fourth position may determine the activity and
      the toxicity. These days a great attention is paid on a synthesis which is
      linking pyrazole and ions of platinum Pt(II) and palladium Pd(III) due to
      anticancer properties but pharmacology is not known very well.

PMID- 18634275
TI  - [Distal radius fractures].
AB  - Distal radius fractures are most common bone fractures. Incidence rate of the
      distal radius fractures are 2 per 1000 person-years. Complicated morphology and
      biomechanics of the fracture and high percentage of complications cause many
      clinical problems in the course of treatment. Detailed examination and
      appropriate choice the method of treatment allows to reduce the complications
      rate. Despite of 200 years research distal radius fractures are still great
      clinical problem.

PMID- 18634276
TI  - [Impact of stress on plasticity of brain structures and development of chosen
      psychiatric disorders].
AB  - The emotional state of human being may lead to sustained changes in structure of
      central nervous system. That is why the role of stress in pathogenesis of mental
      diseases becomes so important. Stress in its wild meaning, not only has an
      influence on neurotransmitting in central nervous system, but also through varied
      neuroendocrine and immunological mechanisms takes effect in permanent brain
      changes. Changes in stress regulating mechanisms as well as activating
      cooperating neurotransmitters seem to play fundamental role in pathogenesis of
      particular mental disorders. Lately, authors pay special attention to the role of
      trauma in development of psychosis. Many researchers underline the role of PTSD
      in decreasing hippocampus capacity. Oversecretion of cortisol being result of
      severe stress seems to be the hypothesis explaining decreased hippocampus
      capacity through initiating neurodegenerative processes. Awareness of negative
      effects of stress should result in undertaking prevention as well as appropriate
      therapeutic approach among people exposed to stress.

PMID- 18634277
TI  - [Delirium--not only psychiatric issue].
AB  - Delirium presents as a diagnosis joining closely other medical disciplines.
      Because of its serious prognosis, precise causal diagnostic is required.
      Selective therapy, to avoid serious prognosis, is possible when delirium is early
      diagnosed and ethiology is established. The present work is to remind risk
      factors of delirium, to explain mechanisms responsible for development of
      delirium based on various etiology, show biomarkers helpful in making diagnosis,
      and pay special attention to prodromal symptoms and clinical forms.

PMID- 18634278
TI  - [Ocular changes in internal carotid artery diseases caused by artheriosclerosis].
AB  - The aim of the study was to show ocular changes in internal carotid artery
      diseases caused by artheriosclerosis and their etiology. Internal carotid artery
      supply blood to the organ of vision, therefore pathologies of those arteries
      caused by artheriosclerosis may have direct influence on its functioning. Most
      common syndromes are temporary (amaurosis fugax) or constant reduction of visual
      acuity. In fundus examination central retinal artery occlusion and branch retinal
      artery occlusion are most common diagnosis, retinal vein occlusion, anterior
      ischemic optic neuropathy, ocular ischemic syndrome are less common. An
      ophtalmologist might be the very first specialist whom patient with internal
      carotid artery disease will visit. Proper recognition and diagnosis of disease
      may protect patient against serious life-threatening complications like stroke.

PMID- 18634279
TI  - [Platelet- derived growth factor--the construction, role and it's receptors].
AB  - CONSTRUCTION: The platelet- derived growth factor (PDGF) is a small protein which
      is produced by many cells. PDGF was originally identified in platelets and in
      serum. It is a dimeric molecule consisting of disulfide- bonded, structurally
      similar A- and B- polypeptide chains. There are four isoforms of PDGF: PDGF A,
      PDGF B, PDFG C and PDGF D. There are purified from the alpha-granules of the
      platelets. ROLE: PDGF is a critical regulator of mesenchymal cell migration and
      proliferation. It is essential for angiogenesis, embryogenesis and cancer
      development and progression. Clinical studies reveal that aberrant expression of
      PDGF and its receptors is often associated with a variety of disorders including
      atherosclerosis, fibroproliferative diseases of lungs and kidneys. RECEPTORS:
      There are two structurally related PDGF- receptors, each with its own variation
      in signaling mechanism. Each subunit of PDGF binds one receptor subunit, leading
      to receptor dimerization. The receptors are tyrosine kinases. PDGFR alpha binds
      all types of isoforms. PDGFR beta can bind only polypeptide B.

PMID- 18634280
TI  - [Cell adhesion molecules and their participation in the process of inflammation
      and cancerogenesis].
AB  - Cell adhesion molecules (CAMs) determine the integral part of protein of cell
      membranes. CAMs mediate in the reception and the transformation of the
      information from the external environment. Then CAMs mediate in the transfer of
      the information in the from of the signal to each fine structure. The
      inflammation process, in which the whole family of cell adhesion molecules takes
      place, is a state which leads to cancer or tumor metastasis. We observe in the
      cancerogenesis process a disturbance of the cell adhesion and proliferation, as
      well as scaled-down integrality between cell and intercellular matrix. CAMs
      function suggests that they play a very important role in inflammation the
      neoplasia process. It use can be found in the early pathogenesis cancer disease.

PMID- 18634281
TI  - [Angiogenesis in the chronic inflammatory diseases and malignancies].
AB  - Angiogenesis is a process of creating new vessels which is necessary in
      pathogenesis of many diseases and disorders like inflammatory or malignancies. A
      lot of markers, both stimulating and inhibiting can influence on this process.
      Knowledge about angiogenesis and its markers, e.g. Vascular Endothelial Growth
      Factor (VEGF), basic Fibroblast Growth Factor (bFGF) can be used in diagnosis and
      treatment of diseases like malignancies. For these reasons summary of these
      processes seems to be very important and valid.

PMID- 18634282
TI  - [Left ventricular systolic function, paced QT dispersion, exercise tolerance and
      quality of life in long term follow up after ventricular pacemaker implantation
      (VVIR) and radiofrequency atrioventricular junction ablation in drug refractory
      atrial fibrillation].
AB  - THE AIM OF THE STUDY was to analyze left ventricular systolic function and
      dimensions, paced QT dispersion (QTD), exercise tolerance (six minute walk test-
      M6) and quality of life (QOL) after RFAVJ in a 6-month (6m) and a 24-month (24m)
      follow-up. MATERIAL AND METHODS: RFAVJ was performed in 30 pts (18 men and 12
      women) aged from 43 to 81 years (mean age 69.8+/-11.3). AF was first diagnosed
      from 2 to 9 (mean 5+/-2.1) years prior to ablation. All patients received VVIR
      pacemakers. Pacing rate was programmed at 80 bpm. Prior to RFAVJ all patients
      underwent: transthoracic echocardiography (ECHO) to assess the left ventricular
      ejection fraction (EF), ventricular end-diastolic and end-systolic dimension
      (LVDD, RVDD, LVSD, respectively) and left atrial dimension; QOL assessment based
      on self-evaluation using: a questionnaire of the SF-36, Manolis, DASI scale. M6
      on flat surface. These examinations were repeated at 6m and 24m after ablation.
      The maximum QT interval (QTM), minimum QT interval (QTm) and QTD were measured
      from the 12-lead ECG after RFAVJ on the first day (1d) and at 6m, 24m following
      RFAVJ. RESULTS: SF total increased from 73.4 to 96.3 (p < 0.0025) in 6m, and to
      113.8 (ns) in 24m, symptomatic score from 15.7 to 20.8 (p < 0.025) in 6m, and to
      22.4 (ns) in 24m, DASI from 39.3 to 46.1 (p < 0.01) in 6m and decreased to 23.9
      (p < 0.001) in 24m. Any significant changes in EF and the remaining ECHO
      parameters in 6m were observed. At 24 m we found significant decreased in EF (p <
      0.01) and increased in LVSD (p < 0.05). Parameters of the M6 significantly
      improved. A significant correlation was observed between the SF-36 and functional
      symptomatology and DASI in 6m. The mean QTm, QTM and QTD were unchanged.
      CONCLUSIONS: 1. In pts with drug refractory AF, RFAVJ and VVIR significantly
      improve QOL and M6. 2. At long term follow up a significant decrease in EF and
      increase in LVSD were demonstrated. 3. No significant changes in the paced QT and
      QTD were observed.

PMID- 18634283
TI  - [Colonization (infection) of the respiratory tract in outpatients in 2000-2005
      years].
AB  - Infections of the respiratory tract are one of the main causes of family doctor
      visiting. A variety of etiological factors (mostly viruses, typical and non
      typical bacteria) causes that the diagnosis of these infections is rarely made in
      outpatient practice (usually these are nose and throat smears); additionally the
      carrier state of typical bacteria in the respiratory tract impedes the
      interpretation of microbiological results. THE AIM OF THE STUDY was to assess the
      incidence of potential bacterial etiological factors of respiratory tract
      infections in outpatients in the years 2000-2005. MATERIAL AND METHODS: The 3270
      microbiological results obtained from patients at the age of between 1 month and
      88 years old with chronic and acute symptoms of respiratory tract infections were
      analyzed. RESULTS: The positive results of bacteria culture indicating the
      possible bacterial etiological agent of infection were found from 1051 patients
      (34.4%), mostly in autumn - spring time. Most often were isolated: H. influenzae 
      28.8%, S. pneumoniae - 22.1% and S. aureus - 22.1%, in less percentage M.
      catarrhalis - 14.1% and S. pyogenes - 13.1. Positive bacteria cultures were
      received most often from ear secretion- 66.8% (P. aeruginosa, S. aureus), from
      nose-41.2% (S. pneumoniae, H. influenzae), sputum - 34.9% (S. aureus), throat -
      24.3% (H. influenzae, S. pyogenes). CONCLUSIONS: It has been confirmed that
      predominant participation of viruses in respiratory system infections is observed
      and also seasonal character of their bacterial nature occurrence (35%). Most
      often were isolated: H. influenzae, S. pneumoniae, S. aureus, also M.
      catarrhalis. On the ground of carrier state of these bacteria in nasopharynx it
      is a clinician's decision to recognize the bacteria as the etiological agent of
      infection and possible use of antibiotic treatment.

PMID- 18634284
TI  - [Evaluation of insulin-like growth factor-1 influence on PECAM-1 and ICAM-1
      adhesion molecules expression on human umbilical endothelial cells surface].
AB  - Activation, proliferation and regeneration of endothelium form developmental
      background of many pathological states. In those processes adhesion molecules and
      growth factors are crucial. Insulin-like growth factor-1 (IGF-1) is important
      regulator of vascular function, expressing pleiotropic actions. Interactions
      between endothelial cells and growth factors are complex and environment
      dependent. THE AIM OF THE STUDY was to assess IGF-1 influence on PECAM-1 and ICAM
      1 adhesion molecules expression on human umbilical endothelial cells (HUVEC).
      MATERIAL AND METHODS: Material for study was obtained from fresh umbilical cord.
      Cell lines were incubated with IGF-1 concentrations of 50 ng/ml and 200 ng/ml.
      Ratio of PECAM-1 and ICAM-1 expression revealing cells was obtained using the
      flow cytometry method. In statistic analysis ANOVA test and Duncan's new multiple
      range test were used. RESULTS: It was demonstrated, that IGF-1 concentrations of
      50 ng/ml and 200 ng/ml enhance PECAM-1 and ICAM-1 endothelial cells expression
      (respectively to 57.2+/-4.8%, 76.1+/-1.5% and 91.7+/-5.0%, 86.8+/-4.7%) compared
      to control group (respectively: 20.9+/-0.5% and 26.6+/-0.5%). CONCLUSION: Insulin
      like growth factor-1 enhances PECAM-1 and ICAM-1 adhesion molecules expression on
      HUVEC cells, activating the endothelium.

PMID- 18634285
TI  - [Analysis of vesicoureteral reflux (VUR) course in children].
AB  - A small number of reports evaluating early effects of vesicoureteral reflux
      conservative therapy in children, based on antibacterial prophylaxis combined
      with correction of the of lower urinary tract function inspired us to perform the
      study. THE AIM OF THE STUDY was to assess the effects of vesicoureteral reflux
      (VUR) management in children according to grade, sex and way of treatment.
      MATERIAL AND METHODS: The study group consisted of 108 children, who were treated
      in 2000-2007 due to VUR. There were 162 refluxing ureters (grades I-V) diagnosed
      by voiding cystourethrography (VCU). In 82 children cystometry and (or)
      uroflowmetry were additionally performed, which revealed lower urinary tract
      disorders in 41 (60 refluxing ureters), mostly detrusor hyperactivity or detrusor
      sphincter dyscoordination. All children had conservative treatment, A - in 67
      (102 refluxing ureters) only antibacterial prophylaxis, B - in 41 of children (60
      refluxing ureters) in combination with pharmacological treatment of urodynamic
      abnormalities. RESULTS: The check-up VCU was performed after 23+/-15 months on
      average. VUR was observed to subside in 44/162 (28%) of refluxing ureters,
      including 22/108 (22%) of those treated managed with method A and 22/60 (37%)
      with method B. Fifty three of refluxing ureters were qualified for further
      conservative therapy and 65/162 (40%) for surgery (especially endoscopic).
      Following 2-3 years medical and surgical treatment, 87/162 (54%) refluxing
      ureters resolved. CONCLUSION: In the diagnostics of VUR in children we should
      take into consideration the assessment of lower urinary tract function, as
      treatment of these abnormalities increases the effects of VUR conservative
      management. However it should be confirmed on a larger group of patients.

PMID- 18634286
TI  - [Endoscopic picture of esophagitis in children with primary and secondary acid
      gastroesophageal reflux].
AB  - THE AIM OF THE STUDY was to assess the esophageal mucous membrane in children
      with pathological acid gastroesophageal reflux (GER) primary and secondary to
      cow's milk allergy and (or) food allergy (CMA/FA), dependent on the duration of
      the disease (prospective study). MATERIAL AND METHODS: 264 children of both sexes
      suspected of GER were enrolled in the study. The age of examined children was 1.5
      102 months (mean age 20.78+/-17.23 moths). Pathological acid GER was confirmed in
      138 children (52.3%) with pH-monitoring. Taking into consideration complex
      differential diagnosis, including elimination of noxious nutrient and oral food
      challenge test (open or blind study), acid GER was differentiated into primary
      and secondary. Children were assigned into study groups 1 and 2. Group 1: 76
      patients (28.8%) aged 4-102 months (mean age 25.2+/-27.28 months) with primary
      GER. Group 2: 62 patients (23.5%) aged 4-74 months (mean age 21.53+/-17.79
      months) with GER secondary to CMA/FA. Endoscopic examination of the upper
      gastrointestinal tract was performed in 138 children: preliminary and control
      examination (after one year and two years of GERD diagnosis. RESULTS: Esophagitis
      of different intensity (second - fourth degree) in macroscopic assessment was
      diagnosed in 25 children (32.9%) with group 1 and in 29 children (46.8%) with
      group 2 in preliminary study. Esophagitis was still present in macroscopic
      assessment after one year of conservative treatment in 13 children (17.1%) from
      group 1 and in 12 children (19.4%) from group 2. After two years of clinical
      observation and periodically administered conservative treatment mild esophagitis
      still persisted in 3 children (3.9%) from group 1, and in 3 children (4.8%) from
      group 2. CONCLUSION: Esophagitis of various intensity (second - fourth degree)
      was diagnosed in preliminary endoscopic examination in about 33% of children with
      group 1 and 47% of children with group 2.

PMID- 18634287
TI  - [Assessment of bone mineral density in children with celiac disease].
AB  - To the reasons of disturbances of bone mineralization in celiac disease belong:
      absorption impairment due to the changes in mucosa including calcium and vitamin
      D adsorption, the activation of osteoclasts by proinflammatory cytokines and the
      decrease in concentration of growth hormone and IGF-1 in the serum. THE AIM OF
      THE STUDY was to analyze mineral bone density in children with celiac disease.
      MATERIAL AND METHODS: Analysis included 37 children aged 5 to 17 years, treated
      in our clinic since November 2004 to June 2007 with diagnosed celiac disease. In
      all children examination of total body bone mineral density (TBMD) was performed
      using DPX(+) densitometer (Lunar). RESULTS: The disturbances of mineral bone
      density were observed in 15 out of 37 children with diagnosed celiac disease
      which amounted to 40.5%. In patients with celiac disease diagnosed de novo such
      disturbances were present in 75%. CONCLUSIONS: The reduction of mineral bone
      density was present in 40.54% of children with diagnosed celiac disease and in
      75% of patients with celiac disease diagnosed de novo. The decrease of BMD
      correlated with nutritional status and was present only in 30% of properly
      nourished children and in much higher percent in severely malnourished children.
      Reduced bone mineral density was observed in 50% of children with mucosa villous
      atrophy and merely in 8% with proper small intestine mucosa. There is a need of
      diagnostic scheme for early diagnosis (screening) and treatment of mineral bone
      density disturbances in children with celiac disease.

PMID- 18634288
TI  - [Relationship between bone mineral content and growth disorders in children with
      juvenile idiopathic arthritis].
AB  - In chronic inflammatory processes in children efforts are made to evaluate bone
      mineral content (BMC) with the use of densitometric parameters, which at the same
      time determine equivalent of lean body mass (LBM). This functional analysis of
      the musculoskeletal system by using DXA method seems to be particularly useful
      for the examination of bone mass in children suffering from juvenile idiopathic
      arthritis (JIA). THE AIM OF THE STUDY was to assess body mass content having
      regard of the BMC/LBM ratio in JIA children, depending on the degree of growth
      inhibition, disease advancement phase and the therapy applied. MATERIAL AND
      METHODS: The study comprised 97 children aged 5-18 (mean age 12.7+/-3.8 years),
      45 girls and 52 boys with diagnosed JIA according to ILAR criteria of 1997. The
      average duration of disease was 4.1+/-3.1 years. Antropometric and densitometric
      measurement was made in every child. Body height was defined by Standard
      Deviation Height Velocity Score - SDHVS (SDS). Patients were divided into 2
      groups: I - 28-group with SDS ratio < -2.0; 11 - 69 children with normal height.
      For the evaluation of disease development and advancement of anatomic changes in
      joints criteria of Steinbrocker were applied: I grade - without joint damage, II 
      insignificant or moderate joints damage, III-IV - established deformation. The
      densitometric research was conducted with the use of double-energy X-ray
      absorptiometry (DXA) method. Bone mineral density (BMD) was assessed in the whole
      skeleton (TB BMD), in the vertebras L2-L4 (SB MD), Z-score index for SBMD and
      BMC, LBM, TB BMC/LBM defined by the Z-score index and compared to norms for age
      and growth. RESULTS: Bone mineral density defined as Z-score index for SBMD <-2.0
      was reported in 21 children (21.6%). Muscle-skeletal Z-score index for TB BMC/LBM
      in relation to norms of gender and growth lower than -1.0 was proved in 23
      children (23.6%). Considerably lower Z-score index for TB BMC/LBM (p < 0.01)
      characterized children with growth inhibition and children with significant
      joints damage (p < 0.02). There was no significant correlation between
      densitometric parameters and applied treatment with glucocorticoids and without
      glucocorticoids. CONCLUSIONS: Decrease of bone mineral mass defined as muscle
      skeletal Z-score index for TB BMC/LBM was found in almost quarter of patients
      within the group of JIA children. In the group of children with growth deficiency
      and with larger joints damage bone mass was significantly lower.

PMID- 18634289
TI  - [The effect of surgical and nutritional treatment on activation parameters of
      peripheral blood T lymphocytes in stomach cancer patients in postoperative
      period].
AB  - Several studies have reported that patients with stomach cancer are frequently
      affected by malnutrition. Malnourished patients are at risk of postoperative
      complications. Immune function starts to deteriorate when weight loss exceeds
      15%. Early enteral nutrition support reduces postoperative lymphocytopenia. T
      lymphocytes are central elements of the immune system. CD69, CD25 and HLA-DR
      molecules are expressed following activation on T lymphocytes surface. THE AIM OF
      THE STUDY was to assess the effect of surgery and early postoperative enteral
      nutrition on peripheral blood T lymphocytes activation status in stomach cancer
      patients. MATERIAL AND METHODS: Lymphocyte T CD: CD3/CD69, CD3/CD25, CD3/HLA-DR
      were determined in 30 stomach cancer patients before treatment and 1, 3, 7 and 10
      days after gastrectomy. Patients received early enteral nutrition from 20 hours
      to 7 days after surgery. The obtained results were compared with the results of
      30 healthy volunteers. RESULTS: The significant deficiency of total T lymphocyte
      number was found in stomach cancer patients before surgery and in postoperative
      period in comparison with the control group. The populations of CD3+/CD69+,
      CD3+/CD25+ and CD3+/HLA-DR+ T lymphocytes in patients with stomach cancer were
      significantly higher in comparison with healthy donors. The significant increase
      of percentage of activated T lymphocytes was observed, too. CONCLUSIONS: The
      obtained data demonstrated significant quantitative defect in T lymphocytes and
      significant increase of their activation status in stomach cancer patients.
      Surgical procedure intensified changes that were observed before treatment. The
      most dynamic changes were observed in CD3+/CD69+ T cells population.

PMID- 18634290
TI  - [Collagen type I gene polymorphism in children and young adults with neoplastic
      disease].
AB  - Osteoporosis has multifactorial and poligenetic basis. One of the most important
      genetic factor, often associated with increased susceptibility to fractures and
      lower bone mass, is the polymorphism of the gene of collagen type I alpha 1
      (COLIA1). Significant ethnic differences were found in the distribution of
      specific COLIA1 genotypes. Comorbidity of potentially unfavourable genotype and
      childhood cancer and its' treatment could enhance its' negative influence on
      bone. THE AIM OF THE STUDY was to evaluate the frequency of collagen type I alpha
      1 gene polymorphism in children from the north-eastern region of Poland, who
      underwent cancer. MATERIAL AND METHODS: The COLIA1 gene polymorphism was
      established by RFLP (restricted fragment length polymorphism) method using
      polymerase chain reaction (PCR) in 215 patients (89 girls and 126 boys) treated
      for cancer at the Department of Pediatric Oncology of Medical University of
      Bialystok. Control group consisted of 51 healthy children from the same region of
      Poland. RESULTS: In the group of children with neoplastic disease we found the
      following distribution of COLIA genotypes: SS - 66,5%, Ss - 33,02% and ss -
      0,47%. In the control group the SS genotype was more frequent (80,95%). In
      children treated for leukemia allel 's' was found to be more frequent (SS - 58%,
      Ss - 41%). CONCLUSIONS: It seems that presence of 's' allel, which was proved to
      be concomitant with fractures occurrence in adults, should be also considered as
      an additional negative element of the bone structure in children, especially when
      other environmental factors are present (complex antineoplastic treatment, bone
      marrow infiltration and cancer itself). Genetic factors, such as polymorphism of
      collagen type I, should be taken under consideration in diseases which can
      potentially lead to osteoporosis.

PMID- 18634291
TI  - [Activity of vestibular organ in people using mobile phones professionally].
AB  - Mobile phones emit radio frequency radiation from 800 to 2200 MHz. Such radiation
      is considered to provoke negative reactions in the human body. The radiation dose
      depends mostly on the exposure time, i.e. telephone connection time, and
      technical parameters of the devices. Clinical and experimental studies so far
      have not provided us with a clear statement about the consequences of this
      radiation on humans. MATERIAL AND METHODS: Taking into account the possibility
      that radiation may have an impact on the nervous system, the authors conducted an
      assessment of labyrinth (vestibular organ) reaction in 50 subjects exposed to
      mobile phones for periods of many years. The results were compared to a group of
      100 subjects not experiencing such exposure. CONCLUSION: No statistically
      significant differences pointing to a negative impact of radiation on labyrinth
      reaction in humans were observed.

PMID- 18634292
TI  - [Vestibular rehabilitation of vertigo and dizziness].
AB  - THE AIM OF THE STUDY was to assess the effectiveness of kinesitherapy in vertigo
      and dizziness. MATERIAL AND METHODS: One hundred thirty two patients with vertigo
      and dizziness, aged 19-71, treated by kinesitherapy and pharmacotherapy were
      examined. The control group consisted of 126 patients treated by pharmacotherapy
      alone. The effects of therapy were assessed by patients' self-control cards and
      electronystagmography (ENG) examinations. CONCLUSION: Kinesitherapy is an
      effective complementary method of treating patients with vertigo and dizziness.

PMID- 18634293
TI  - [Extrapulmonary tuberculosis in the patients of otholaryngology department--case
      reports].
AB  - Tubercle bacillus infection is widespread in all areas of the world and affects
      one-third of the human population. Tuberculosis can affect each organ in the body
      and although the most common presentation is pulmonary tuberculosis it can also
      develop in laryngological organs. THE AIM OF THE STUDY was the analyze
      symptomatology and also the diagnostic and therapeutic process of tuberculosis in
      the larynx, the lymph nodes of the neck, the ear and the palatine tonsils.
      MATERIAL AND METHODS: The evaluation of medical documentation of 9 patients
      hospitalized in department of otholaryngology in the period of last 4 years was
      conducted. In all of them extrapulmonary tuberculosis developed in tissues and
      organs of the upper respiratory tract, neck and middle ear was detected. RESULTS:
      In the analyzed group there were 5 women and 4 men. The age of patients varied
      from 40 to 75 years (average 56.3). In the examined group there were three cases
      of the larynx tuberculosis, three cases of tuberculosis of the lymph nodes, two
      cases of the ear tuberculosis and one case of tuberculosis of the palatine
      tonsils. CONCLUSIONS: The source of the diagnosis in analyzed cases was first of
      all histopathological examination. Tuberculosis process found in the area of
      middle ear and palatine tonsils imitated chronic, non-specific inflammation and
      in the case concerning the ear was the only location of the illness. Tuberculosis
      of larynx in all the patients co-existed with specific changes in lungs and took
      the form of tumors suggesting neoplasmatic background of the disease.
      Tuberculosis of the lymph nodes can take the form of the neck abscess.

PMID- 18634294
TI  - [Insulinoma misdiagnosed and treated as epilepsy].
AB  - Although insulinoma constitutes almost 90% of neuroendocrine tumors localized in
      the pancreas, it is a rare disease. Quite commonly prior to the diagnosis there
      is a history of several years and misdiagnosis as neurological or cardiological
      disease is not infrequent. Patient, 22 years old, since 7 years experiencing
      multiple incidents of neuroglycopenia with concurrent hyperadrenergic reaction.
      Consciousness disturbances and muscle tremor together with feeling of hunger and
      tachycardia occurred mainly in the morning hours, or after physical exercise, and
      subsided after glucose intake. Increase in body weight, typical for insulinoma,
      was also observed. The patient was hospitalized twice in Pediatric Department and
      although hypoglycemia was observed, no additional testing was performed to
      exclude insulinoma; reported symptoms and abnormalities in EEG recording after
      provocation resulted in diagnosis and treatment of epilepsy. During
      hospitalization in the Department of Endocrinology fasting test was performed,
      which revealed inadequately high insulin level with glucose level of 41 mg% and
      signs of neuroglycopenia. The image of pancreas was normal in the acquired
      abdominal ultrasound and in CT a tumor was found in the tail of pancreas. The
      patient underwent laparoscopic operation and the clinical diagnosis was confirmed
      by histopathology. Antiepileptic drugs were discontinued. Total remission of
      symptoms was achieved. The presented case demonstrates the difficulties in
      correct interpretation of reported symptoms, while the results of biochemical
      tests and imaging studies point precisely to the diagnosis. Focal neurological
      signs resulting from multiple episodes of hypoglycemia may lead to misdiagnosis
      and treatment of epilepsia.

PMID- 18634295
TI  - [Partial splenectomy for splenic cyst--fifteen years follow-up of surgical
      treatment].
AB  - Secondary cysts of the spleen are uncommon and usually result from blunt
      abdominal trauma. Symptomatic cysts and those with diameter above 5 cm are
      indications for surgical treatment. Spleen parenchyma preserving operations,
      currently recommended, reduce the risk of early and late septic complications,
      particularly overwhelming postsplenectomy sepsis. Partial splenectomy offers a
      definitive treatment of a splenic cyst while preserving splenic functions. The
      author describes the case of a patient with spleen lower pole pseudocyst, 14 cm
      in diameter, subjected to partial splenectomy in 1992. Healthy spleen parenchyma
      was cut with an electrocoagulation knife at a distance of 1.5 cm from the cyst
      edge. Local hemostasis was assured with mattrees absorbable tape polyglycolic
      acid sutures and fibrin glue injection into resection plane. Complications were
      not observed. Long-term, fifteen years follow-up revealed preservation of splenic
      function and no septic complications. CONCLUSION: Partial splenectomy, demanding
      high technical experience procedure, is the treatment of choice of the splenic
      cyst.

PMID- 18634296
TI  - [Erythema gyratum repens Gammel without internal cancer--case report].
AB  - Erythema gyratum repens Gammel is a rare illness that almost always accompanies
      the tumour of internal organs. The case of 63 year-old women with the clinical
      and histological recognition of Erythema gyratum repens Gammel without the
      accompanying tumour will be introduced. The exanthema had the character of
      swelling, itchy erythemas that very quickly (in a few days) started widening
      concentrically, forming the typical ring-shaped pattern reminding grains. Mucous
      membranes were free from changes. Laboratory and pictorial examination did not
      show any significant deviations. According to the histopathological examination
      the clinical recognition turned out to be true. During the hospitalization, in
      spite of treatment (steroids - medium dose, anti-histamine drugs and external
      steroids therapy) a progression of skin changes and appearance of some new single
      changes were observed. At present the patient is under constant ambulatory
      control in order to keep the exanthemas under intensive oncological alertness.

PMID- 18634297
TI  - [Budd-Chiari syndrome--from diagnosis to treatment--case reports].
AB  - Budd-Chiari syndrome is a rare disease, caused by obstruction of the hepatic
      venous outflow at the level of either the large hepatic veins or (and) the
      subdiaphragm segment of the inferior vena cava. The hematological disorders
      (myeloproliferative disorders, factor V Leiden deficiency), tumor and chronic
      inflammatory diseases are the most frequent causes of BCS in Europe and North
      America. Two cases of BCS, recognized in 24 and 43 years old females with
      subacute and chronic forms of the disease are presented in this article. The
      underlying cause was polycythemia rubra vera and osteomyolofibrosis. In first
      case, except causal and anticoagulation therapy, a transjugular intrahepatic
      portosystemic stent has been performed. In the second one low - sodium diet and
      diuretic for the control of ascites and oedemas were used. Hydroxycarbamid was
      the first choice line medication in treatment hematological disorders and
      acenocumarol in the prevention of the trombotic complications.

PMID- 18634298
TI  - [Cerebral vasospasm in patient with hemorrhagic stroke after amphetamine intake-
      case report].
AB  - Amphetamine abuse increase risk of hemorrhagic stroke and may result in cerebral
      vasospasm. In this report we present 31 years old male with intracerebral
      hemorrhage subsequent to amphetamine intake. Diffuse cerebral vasospasm was found
      by angiography. Transcranial color coded Doppler sonography was applied for
      vasospasm monitoring and pharmacological treatment after surgical removal of the
      intracerebral hemorrhage. Basing on this case we can conclude that cerebral
      vasospasm should be suspected in patient with amphetamine abuse and hemorrhagic
      stroke.

PMID- 18634299
TI  - [Health related quality of life in patients with peripheral arteries and veins
      pathology].
AB  - In the last years we can observe a great progress of medical technologies. Every
      year a new diagnostic and therapeutic methods are developed. Quite often the
      outcomes of the treatment with those technologies are very similar. Typical
      methods of evaluation, like time of survival or results of laboratory tests are
      not enough to make a proper choice between available technologies. From the other
      hand medical professionals try to respect patients' preferences and needs in the
      treatment process. For these reasons health related quality of life measurements
      are widely used in clinical practice and medical trials, comparing different
      medical techniques. THE AIM OF THE STUDY was to review methods and results of the
      health related quality of life assessment, in patients with peripheral vascular
      pathology diagnosed. The authors reviewed available bibliography on quality of
      life measurement tools, used in patients with peripheral vascular pathology.
      Those instruments and the results of the studies, performed with them have been
      described. Health related quality of life measurements are a valuable, additional
      method of treatment outcomes evaluation in patients with peripheral vascular
      pathology. They often help to estimate the influence of the treatment on
      patients' life, in its physical emotional and social aspects. In the few last
      years the quality of life assessment has been included into the protocols of few
      randomized international clinical trials, what proves wide acceptance of such
      studies.

PMID- 18634300
TI  - [Toxoplasmosis--parasitosis with a variety of appearances].
AB  - By 2008 Toxoplasma gondii will have been known for 100 years as a parasitic
      protozoan, which is an etiological agent of toxoplasmosis in animals and humans.
      Despite very intensive research, many biological and medical aspects of the
      invasion with this parasite have not been satisfactorily explained. In the
      article, some recent observations on epidemiology, biology, and physical as well
      as psychical consequences of the Toxoplasma gondii infections were described and
      commented on.

PMID- 18634301
TI  - [Matrix metalloproteinases in the central nervous system: clinical significance
      and therapeutic prospects].
AB  - Matrix metalloproteinases (MMPs) were originally described as proteases capable
      of degrading extracellular matrix components. Increasing evidence indicates a
      much more complex role of MMPs. Diverse functions of MMPs include cellular
      differentiation, migration, survival or death, angiogenesis and signalling.
      Metalloproteinases are crucially involved in a number of inflammatory conditions
      in the central nervous system facilitating blood-brain barrier breakdown,
      leukocyte recruitment and shedding of cytokines and growth factors. These enzymes
      contribute to pathogenesis of meningitis, multiple sclerosis and
      neurodegenerative disorders. While most studied in the context of disease,
      beneficial role of metalloproteinases during nervous system development and
      following injury is now being appreciated. The present study aimed at reviewing
      clinical relevance of these enzymes and potential therapeutic prospects for the
      coming future.

PMID- 18634302
TI  - [Conventional X-ray study in the diagnosis of esophageal achalasia and at its
      treatment stages].
AB  - The paper deals with one of rather common and clinically urgent diseases of the
      esophagus--esophageal achalasia (EA). By using 173 cases as an example, the
      authors show a diversity of clinical symptoms and basic X-ray diagnostic criteria
      for this abnormality. Analysis of the results of clinical and instrumental
      studies has enabled the authors to differentiate the complicated and
      uncomplicated forms of the disease, identification of which determines the choice
      of an algorithm of complex treatment. The paper provides strong evidence that the
      classical techniques of a conventional X-ray study ensure a valid differential
      diagnosis of EA and cardioesophageal cancer and evaluates the efficiency of
      treatments.

PMID- 18634303
TI  - [Capacities of ultrasound study in the diagnosis of diffuse gastric carcinoma].
AB  - By using 237 verified cases of diffuse carcinoma and benign diseases of the
      stomach as an example, the authors assess the capacities of routine
      transabdominal ultrasound study (USS) of the stomach in the diagnosis of tumors
      and present their modification of the procedure facilitating the imaging of
      problem areas. In the authors' opinion, the symptoms of thickening of the wall of
      the stomach and abnormalities in its normal five-layered structure indicate
      diffuse gastric carcinoma. The authors consider USS to be a supplement to the
      basic diagnostic techniques--X-ray study and gastroscopy.

PMID- 18634304
TI  - [Ultrasonography in the diagnosis of colonic obstruction].
AB  - The authors of the present paper outline the results of studying the use of
      routine transabdominal sonography and ultrasound irrigoscopy (UI) in the
      diagnosis of acute colonic obstruction (ACO) in 70 patients. The cause of ACO was
      tumor-induced colonic luminal obturation in 55 patients and colonic evacuatory
      dysfunction due to congenital anomalies and acquired constrictions of
      inflammatory genesis in 15 cases. UI was used to determine the presence, degree,
      and causes of colonic obstruction. The paper details the UI procedure developed
      by the authors and the ultrasound semiotics of ACO, shown by routine
      transabdominal sonography and UI. Analysis of the results of the studies allows
      the authors to state that UI is as highly informative as X-ray irrigoscopy in the
      diagnosis of ACO and may be included into a diagnostic algorithm in these
      patients.

PMID- 18634305
TI  - [Radiation studies in the detection of early signs of lung tissue lesion in
      sarcoidosis].
AB  - The capacities of various radiation techniques in the study of patients with
      pulmonary sarcoidosis are analyzed. The sequence of their use, which ensures a
      high informative value, is proposed. By analyzing the X-ray semiotics in 45
      patients with pulmonary sarcoidosis, the authors give the diagnostic signs of
      early lung parenchymal damage in this disease. Particular emphasis is placed on
      the procedure of lung X-ray computed tomography.

PMID- 18634306
TI  - [Magnetic resonance imaging in the diagnosis and treatment of hernias of thoracic
      intervertebral disks].
AB  - Magnetic resonance imaging (MRI) was carried out in 24 patients with thoracic
      osteochondrosis. The obtained MR images showed the high efficiency of this
      radiodiagnostic technique in solving the tasks of visualizing a degenerative
      dystrophic lesion of the vertebral column. MRI allows one to solve a broad
      spectrum of specific problems facing a radiodiagnostician and a neurosurgeon on
      examining a patient with thoracic osteochondrosis. This study permits an
      objective assessment of the stage of herniation and the degree of spinal cord
      compression, determination of treatment policy, planning of a surgical
      intervention, assessment of the results of surgical treatment, timely detection
      of possible complications, and visualization of recurrent hernia.

PMID- 18634307
TI  - [Hydatid disease of the lung: 2 case reports].

PMID- 18634308
TI  - [A case of misdiagnosis of giant bone tumors].

PMID- 18634309
TI  - [Application of noninteracting probes in the protein structure space for the
      construction of statistical potentials for atom-atom interactions].
AB  - Some effects hindering the construction of knowledge-based potentials of atom
      atom interactions in problems of biopolymer modeling have been considered. It was
      shown that some limitations are overcome by considering the distribution of
      distances between noninteracting probes in the protein structure space. It was
      shown that knowledge-based potentials thus constructed can be effectively used to
      analyze the hydration of protein atoms. Using this approach, it is possible to
      predict the structure water location in a protein globule and recognize the
      correctly folded protein structure among decoys.

PMID- 18634310
TI  - [Electrodynamics of interactions in electrolyte solutions and their biological
      significance].
AB  - Attention is drawn to the fact that the interaction of charges in aqueous
      solutions of electrolytes, such as media having physiological characteristics,
      depends not only on the distance between interacting charges but also on the
      frequency that determines their dynamics. This fact has significant consequences
      for some biological processes and their kinetics. The analysis of reasons for
      charge shielding, including the dynamic effects, shows that, even at distances
      exceeding the Debye length, electric interactions in systems similar to
      physiological are effective provided that charges move with frequencies higher
      than 250 MHz. For each electrolyte solution, the threshold frequency (Maxwell
      frequency) can be found, which determines the transition from the conducting to
      the dielectric mode of interactions of charges in physiological solutions.

PMID- 18634311
TI  - [Geometrical analysis of protein-DNA interactions on the basis of the Voronoi
      Delaune tessellation].
AB  - A new method for the rigorous analysis of DNA-protein contacts has been developed
      on the basis of Voronoi tessellation. This method permits one to determine close
      neighbors on the atomic level and compute the area of contact by edges of Voronoi
      polyhedra. Based on the results of the study of 1109 protein-DNA complexes from
      PDB, it was demonstrated that about one third of the contacts are the contacts
      with positively charged Arg and Lys. There is distinct amino acid prevalence for
      nucleotides: for A - Pro; for T - His; for G - Asp; for C - Trp, Asp, Glu.
      Therefore, GC pairs prefer to interact with negatively charged residues, and
      alanine and methionine, whereas AT pairs prefer to interact with histidine and
      unpolar residues.

PMID- 18634312
TI  - [Structural organization of DNA complexes with proteins HMGB1 and HMGB1-(A+B)].
AB  - The interaction between DNA and the nonhistone proteins HMGB1 and HMGB1-(A+B) has
      been studied using circular dichroism and scanning force microscopy. The
      recombinant protein HMGB1-(A+B) has no negatively charged C-terminal domain
      characteristic for HMGB1. Our earlier suggestion about the structural interaction
      of tandem HMGB1-domains of the recombinant protein with DNA was confirmed. It was
      shown that the C-terminal part modulates the interactions of HMGB1-domains with
      DNA. Without the C-terminal sequence, the HMGB1-(A+B) protein forms DNA-protein
      complexes with the ordered supramolecular structure.

PMID- 18634313
TI  - [Heterogeneity of double-stranded DNA local structure and dynamics: ultrasound
      studies].
AB  - A method for studying the local inhomogeneities of DNA and its dynamics is
      proposed. The method is based on the combination of two procedures, splitting the
      DNA molecules by ultrasound and analysis of DNA fragments obtained by gel
      electrophoresis. The frequency of cleavage of internucleotide bonds was found to
      depend on the type of nucleotides forming the bond and on their nearest
      neighbors. Estimates of cleavage frequencies in each of 16 dinucleotides showed
      that, in the 5'-d(CpG)-3', 5'-d(CpA)-3', and 5'-d(CpT)-3' dimers, the cleavage
      occurs considerably more frequently than in the rest, and the frequency of
      cleavage depends on the nearest neighbors. It was shown that the double-helix
      cleavage can occur with shifts by several nucleotides. Physical prerequisites
      were considered that can lead to this pattern of sequence - specific cleavage.

PMID- 18634315
TI  - [Effect of energy status of hydrogen bond protons on the rate of electron
      transfer in photosynthetic reaction centers].
AB  - We present here a theoretical interpretation of the temperature dependence of the
      rate of dark recombination which takes place in Rhodobacter sphaeroides reaction
      centers between a primary quinone (Q(A)) and a bacteriochlorophyll dimer. Taking
      the energy of interaction between hydrogen bond protons and an excessive electron
      into account, we described qualitative by this nonmonotonous dependence. We
      considered a molecular model of the primary quinone from Rb. sphaeroides reaction
      centers. In addition to the primary quinone, the model includes two reaction
      center fragments that form hydrogen bonds with Q(A). One of these fragments is
      His(M219), and the other is the peptide [Asn(M259) - Ala(M260)]. We used the two
      center approach with regard for electron-phonon interaction in order to calculate
      the characteristic time of electron tunneling during the recombination reaction.
      The energy of the phonon emitted/absorbed during the electron tunneling is
      determined by a relative shift of the donor and the acceptor energy levels, the
      detuning of levels. The value of level detuning was shown to be temperature
      dependent in a nonmonotonous manner in the case of hydrogen bonds with double
      well potential energy surface. The characteristic time (or the reaction rate)
      depends on temperature parametrically. The dependence is nonmonotonous and is in
      qualitative agreement with the experimental one.

PMID- 18634314
TI  - [Temperature dependence of conformational properties of natural lipid oligomer
      chains: computer simulation].
AB  - The conformational properties of several oligomeric chain molecules at T = 278
      and T = 403 K have been studied using Monte Carlo computer simulations.
      Hydrocarbon oligomers with methylene-interrupted cis double bonds in the main
      chain were considered. These oligomers are typical constituents of natural lipid
      molecules. The characteristics of the shape of C-H and C-C bond orientation
      distribution functions with respect to the principal axis of inertia of the
      chains and their temperature dependences were studied. It was found that the
      temperature sensitivity of not only the common geometric characteristics of the
      polyunsaturated chain is significantly reduced compared with the saturated one,
      but also that of local characteristics, i. e., the shape of each bond orientation
      distribution function of the polyunsaturated chain. The relationship between the
      properties of lipid polyunsaturated hydrocarbon chains and their functions in
      natural membrane systems, in particular their possible role in the stabilization
      or optimization of lipid-protein interactions, was discussed.

PMID- 18634316
TI  - [A new methodical approach to the determination of the quantum yield of the
      photoelectric conversion of electronic excitations in reaction centers of purple
      bacteria].
AB  - A new methodical approach has been developed, which enables one to determine with
      a high precision (approximately 1.5%) the quantum yield of energy conversion in
      reaction centers isolated from purple bacterium. This parameter for reaction
      centers from Rhodospirillum rubrum was estimated to be 93.5 +/- 1,5%. Our
      methodical approach makes it possible to calculate quantum yield values for
      complete photosystems of purple bacteria.

PMID- 18634317
TI  - [The efficiency of ATP synthase as a molecular machine].
AB  - On the basis of the experimentally measured isotope effect of magnesium (25)Mg on
      the rate of ATP synthesis by mithochondrial ATP synthase, the rate constants of
      the reactions in the catalytic site have been estimated. The limiting step of the
      synthesis is shown to be the addition of8phosphoryl anion-radical of ADP to the
      P=O bond of phosphate with the rate constant of 1,2 x 10(8) s(-1). From the ratio
      of the rate constants, the mechanochemical efficiency of ATP synthase was
      estimated to be about 10% for enzymes with (24, 26)Mg isotopes and to be doubled
      for enzymes with (25)Mg in the catalytic site.

PMID- 18634318
TI  - [The role of TLR4 receptor in the stress response of lymphocytes].
AB  - In vitro effects of low-level electromagnetic waves (8.18 GHz, frequency swings
      within 1 s, intensity 1 microW/cm, exposure for 1 h) and low-energy laser light
      (He-Ne laser with 632.8 nm, 0.2 mW/cm, dose 1.2 x 10(-2) J/cm2) on the expression
      of receptor protein TLR4, which is known as a part of the system for microbal
      toxin recognition, were studied in mouse lymphocytes. In addition, TLR4
      expression was examined in situations when stress responses to low-level
      nonionizing radiation were modified by the antibiotic geldanamycin, which
      suppresses the activity of the heat shock protein Hsp90. It was found that low
      level microwaves significantly raised the amount of TLR4; in contrast, laser
      light decreased the expression of the receptor in lymphocytes. In cells
      pretreated with geldanamycin, the TLR4 expression in irradiated cells was reduced
      to minimum levels, much lower than control values. The results showed that TLR4,
      which is involved in specific binding of toxin from gram-negative bacteria, can
      regulate cell responses to signals of other origin, in particular to nonionizig
      radiation, including low-level microwaves and laser light.

PMID- 18634319
TI  - [Membranotropic effect of some triterpene glycosides possessing immunostimulating
      properties].
AB  - The peculiarities of the interaction between cell membrane lipids and triterpene
      glycosides from holothurians Apostichopus japonicus S. and Cucumaria japonica
      (holotoxin A1 and cucumarioside A2-2, respectively) were studied in comparison
      with plant saponins from Quillaja saponaria, known as hemolytic, adjuvant, and
      structure-forming components of immunostimulating complexes. Similar to Quillaja
      saponins, the sea glycosides, holotoxin A1 and cucumarioside A2-2 were shown to
      possess a high hemolytic activity (2.6 and 3 microg/ml, respectively) and sterol
      depending membranotropic effect mediated by the formation of nonbilayer sterol
      lipid-glycoside complexes. At the same time, cucumarioside A2-2 bound exogenic
      cholesterol only in the presence of membrane lipids, such as phosphatidylcholine
      or monogalactosyldiacylglycerol, in contrast to Quillaja saponins and holotoxin
      A1, which bound cholesterol in the molar ratios 1:2 and 1:8, respectively.
      Moreover, in all cases, tree-component complexes containing cholesterol, lipid,
      and glycoside exhibited a lower hemolytic activity compared with two-component
      sterol-glycoside complexes. It was concluded that the hydrophobic medium of cell
      membranes performs a potentiative role in the effective interaction between
      triterpene glycosides and "sterol receptors". A method for decreasing the
      toxicity of membranotropic holothurian glycosides possessing the immunomodulating
      properties was suggested.

PMID- 18634320
TI  - [Influence of propagating electrical signals on delayed fluorescence of geranium
      leaves. 1. Experimental analysis].
AB  - It was shown that local damaging stimulation of geranium graft induced the
      generation and propagation of electrical signals (variation potential), which
      changed the parameters of delayed luminescence in the leaf blade. The responses
      of delayed luminescence included two stages, which probably occur by different
      mechanisms.

PMID- 18634321
TI  - [Dynamic filtration of the variability of expression patterns of zygotic
      segmentation genes in Drosophila].
AB  - An analysis of the quantitative data obtained by processing the confocal images
      showed that the early variability of expression patterns of zygotic segmentation
      genes in Drosophila drastically decreases by the time of the onset of
      gastrulation. The following components of variability were examined: the scatter
      of the levels of gene expression in different embryos, the time and sequence of
      the formation of expression domains, the type of their formation, and the domain
      positioning. It was found that the positioning error at the level of zygotic
      genes is dynamically filtered with time.

PMID- 18634322
TI  - [High-frequency oscillations in a pulse wave signal and their relation to
      adaptation responses].
AB  - High-frequency oscillations in a pulse wave signal in the range of 1-50 Hz and
      their relation to heart rhythms have been investigated. Informative parameters to
      estimate the adaptation reactions have been determined using the Kohonen maps,
      the results of simulating the pulse wave signal (single rheocycles), and the
      experimental data. The coefficient of harmonic variation was used as an
      informative parameter. It was shown that the space of signs in the frequency
      range of 1-12.5 Hz, formed on the basis of the coefficient of harmonic variation,
      possesses a significant degree of structuring relative to the distribution of
      data for different types of adaptation reactions.

PMID- 18634323
TI  - [Dynamics of the activity of cerebellar Purkinje cells induced by changes in the
      duration of complex spikes].
AB  - The relationship between complex and simple spikes of Purkinje cells from vermis
      cerebelli of guinea pigs has been investigated. The ratio of complex spikes
      innervated by the processes of one and the same liana-like fiber ("twins cells")
      has also been studied. Three types of complex spikes in each Purkinje cell from
      vermis cerebelli of guinea pigs (n = 44) have been differentiated, which differ
      in duration. It was found that long (10.28 +/- 0.27 ms) complex spikes in all
      cells lead to a more pronounced inhibition of simple spikes than complex spikes
      of short duration (6.08 +/- 0.25 ms). It was shown that the dynamics of duration
      of complex spikes coordinates with changes in the activity of some Purkinje cells
      and their local groups: (a) complex spikes generated before the onset of pauses
      of simple spikes are longer than complex spikes generated before the termination
      of pauses; (b) in "twins cells" innervated by one liana-like fiber, the
      properties of complex spikes change simultaneously; (c) The degree of synchronism
      of complex spikes in closely-spaced (to 150 microm) Purkinje cells receiving the
      inputs from different liana-like fibers increases with their duration. A possible
      functional role and the mechanisms of generation of complex spikes are discussed.

PMID- 18634324
TI  - [The conduction of tonal and compound sounds through the body of a bottlenose
      dolphin].
AB  - The peculiarities of underwater sound conduction through the body of the Black
      Sea bottlenose dolphin (Tursiops truncatus p.) were investigated to elucidate the
      mechanisms of acoustic orientation of marine mammals. By using the method of
      instrumental conditioned reflexes with food reinforcement, underwater hearing
      thresholds in the bottlenose dolphin depending on signal parameters (tonal pulses
      and various noises) and sound conduction pathways were measured under conditions
      of full and partial (with the head out of water and sound being conducted through
      the body tissues) submergence of the animal into water. The underwater hearing
      thresholds increased by 6-27 dB upon sound conduction through the body tissues
      (to the least extent for tonal pulses of 10 and 20 kHz). The hearing thresholds
      for tonal pulses and narrow-band noises were very similar both under conditions
      of full and partial submergence of the animal into water.

PMID- 18634325
TI  - [The localization of the sound source in the vertical plane by a bottlenose
      dolphin].
AB  - The accuracy of localizing the underwater sound source in the vertical-plane by
      the bottlenose dolphin was investigated using the method of instrumental
      conditioned reflexes with food reinforcement. The accuracy of determining the
      underwater sound in the vertical plane (the full angle) was on the average: 2 -
      2,5 degrees for tonal signals with frequencies of 5, 20, and 120 kHz; pulsed
      clicks with the central frequency of 120 kHz and the exponential forms of
      amplitude alteration wavefronts were localized by the dolphin with an accuracy of
      1,5 degrees. Among all marine mammals examined, dolphins are characterized by the
      maximal exact analysis of acoustic space.

PMID- 18634326
TI  - [Characteristics of the acoustic field of interfering reflections and the
      echolocation hearing of the dolphin].
AB  - A model of the acoustic field of interfering reflections from steel cylinders was
      developed. Analysis of the model showed the availability of great potential
      resources for a decrease of the influence of unwanted echoes and hence for
      increasing the signal-to-clatter ratio. The conformity of the available models of
      the echolocation hearing of the dolphin to the acoustic field of the clatter was
      considered. The participation of mandidle mental foramens in conducting the echo
      to the cochlea was considered. In this case the hearing aperture is determined by
      the dimensions of mental foramens, while the hearing base is determined by the
      distance between the mental foramens of the left and right mandible halves. There
      are good reasons to believe that the optimal dimensions of the aperture and the
      base of echolocation hearing of Odontoceti essentially increase the effectiveness
      of defense of their sonar from reverberation.

PMID- 18634327
TI  - [The influence of ultrasound and constant magnetic field on gametes, zygotes, and
      embryos of the sea urchin].
AB  - The influence of constant magnetic field, power 7 T, and ultrasound, frequency 2,
      4 and 8 MHz, on gametes, fertization, embryos and larvae of the sea urchin was
      studied. It was shown that magnetic field breaks the process of the gamete fusion
      but does not influence gametes, embryos, and larvae. Ultrasound impairs the
      motility of spermatozoa and larvae, prevents the fertilization, and breaks the
      embryonic development. It is assumed that the effect of the magnetic field is
      connected with the response of the cortical cytoskeleton, which consists of
      bundles of actin microfilaments. The rearrangement of the cortical cytoskeleton
      occurs during the first 20 minutes after the contact of sperm with the egg. Also
      there is effect of magnetic fields on calcium ions, which are liberated during
      the first seconds after gamete contact. The effect of the ultrasound is explained
      by a small increase in water temperature and cavitation process, which break
      celluar structures.

PMID- 18634328
TI  - [Effect of weak static magnetic fields on the excitability of a neuron].
AB  - Changes in the excitability of the neuron (amplitude, excitability threshold,
      rate of action potential transduction), as well as changes in the viscosity of
      the plasma membrane of the nerve and membranes of subcellular organelles, induced
      by the action of a weak magnetic field, have been studied by the methods of
      extracellular registration of membrane potential and combination scattering. It
      was found that only the threshold of excitability in intact nervous fibers
      increases by the action of this field. It was proven that the conformation of C40
      carotenoids localized not only in plasma membranes but also in subcellular
      membranes of the neuron changes in a weak magnetic field. It is assumed that the
      changes in the excitability of the neuron by the action of weak magnetic field
      are due to changes in the orderliness of membrane lipids and the content of
      oxygen in the cytoplasm.

PMID- 18634330
TI  - [Sterols and their transport in animal development].
AB  - The cellular content of different sterols in invertebrates and vertebrates as
      well as their origin (endogenous and food sources) and significance for the life
      cycle are comparatively reviewed. The initial signaling role of sterols in the
      vital activity (in all multicellular animals) and later obligatory incorporation
      of certain sterols in cell membranes as a plastic components (in vertebrates) are
      proposed based on the presented data.

PMID- 18634329
TI  - [Nucleosomal repeat and the location of exons and introns in genes of collagens
      types I and VII].
AB  - Regions with a quasiperiodical location of exon--intron sites have been found in
      the loci of genes of I and VII type collagens (with a total length of exons more
      than 15% of the entire size of the locus). The periods observed are similar to
      periods typical for the nucleosomal level of the organization of chromatin. It
      was shown that the sites consisting of successively arranged exons and introns
      form groups involving two to five such regions of the same length. The groups
      encoding the fibrillar regions of the gene product contain more than 50% of
      exons. The regions are on the average 165 nt long, which is close to the minimal
      nucleosomal repeat length observed in some regions of the eukaryotic genome. In
      the nonfibrillar region of the gene of VII type collagen, groups of several exon
      intron pairs with an average length of 227 nt were identified. The change in the
      length of exon-introns sites on going from the nonfibrillar to the fibrillar
      moiety occurs in a jump, which is clearly seen on a periodogram of the locus.

PMID- 18634331
TI  - [Growth and differentiation of cell hybrids obtained by fusing mouse PCC4azal
      teratocarcinoma cells and mouse spleen cells under different in vitro culture
      conditions].
AB  - Cell hybrids obtained by fusing mouse PCC4azal teratocarcinoma cells and spleen
      cells induced to proliferation and treated with the demethylating agent 5
      azacytidine prior to fusion are described. The obtained hybrids demonstrated no
      expression of T lymphocyte marker genes CD11 and CD45, which indicates possible
      somatic nucleus reprogramming by factors present in teratocarcinoma cells.
      Irrespective of culture conditions, cell hybrids demonstrated a relatively stable
      chromosome number: they lost on average no more than four chromosomes after 30
      passages. Culturing in medium containing hypoxanthine, aminopterin, and thymidine
      (selective conditions) decreased the differentiation capacity of cell hybrids
      compared to nonselective conditions, which is likely due to the inhibition of
      their metabolism. For the first time, teratocarcinoma cell hybrid differentiation
      into cardiomyocytes under the influence of DMSO has been demonstrated in vitro.

PMID- 18634332
TI  - [Signaling factors of self-organization of protein synthesis rhythm in hepatocyte
      cultures--gangliosides and catecholamines function independently].
AB  - Considering the data on the low level of self-organization (self-synchronization)
      of protein synthesis rhythm in aging, we studied the possible interference of the
      signaling factors of self-organization, gangliosides and catecholamines, as well
      as catecholamine reception. Experiments were carried out on primary cultures of
      rat hepatocytes on slides. Inhibited ganglioside synthesis did not prevent the
      organization of protein synthesis rhythm by the alpha-adrenomimetic agent
      phenylephrine. Upon the blockade of alpha-receptors by prazosin, the protein
      synthesis rhythm was observed after the exposure to gangliosides. Alpha
      adrenolytic agents prazosin and benoxathian abolished the synchronizing effect of
      the beta-adrenomimetic isoproterenol. A mixture of alpha- and beta-adrenomimetic
      agents inhibited the protein synthesis rhythm-organizing effect of noradrenaline.
      Thus, the signaling molecules of self-organization of protein synthesis function
      independently via specific receptors.

PMID- 18634333
TI  - [Survival of transgenic mouse embryos carrying different genetic constructs].
AB  - The survival of transgenic mouse embryos was studied as a function of the
      transgene structure. The data obtained indicate that the introduction of a
      chromosomal DNA fragment providing for the anchoring of interphase chromosomes on
      the nuclear envelope increases the efficiency of transgenesis in mice threefold
      due to their increased viability.

PMID- 18634334
TI  - [Distribution system formation in hydroid polyp development].
AB  - The formation of the pulsatory distribution system, which is the basis of the
      colonial organization in hydroids, was studied in Gonothyrea loveni (Allm.,
      1859). The patterns of the distribution system functioning were established at
      different developmental stages.

PMID- 18634335
TI  - [A study of proteins of annexin group in early fish development. IV.
      Identification of calcium-binding proteins in zebrafish egg by mass
      spectrometry].
AB  - Calcium-binding proteins were isolated from zebrafish (Brachidanio rerio) eggs by
      the method of precipitation with acidic phospholipids in the presence of calcium
      ions. The revealed proteins separated by SDS-PAGE were identified by mass
      spectrometric tryptic peptide fingerprinting. The proteins included annexins A2a,
      A1a, A13.1, and A5. In addition, copine III, a member of the recently described
      copine family of C2 domain-containing proteins, was identified. Total RNA was
      analyzed in mature oocytes by RT-PCR and transcripts of two different annexin A13
      forms (A13.1 and A13.2) as well as of annexin A3 were detected. Thus, the
      presence of both proteins and mRNAs of annexins has been shown in the zebrafish
      egg.

PMID- 18634336
TI  - [Development of hind limb bones in chicken embryos under altered temperature and
      humidity conditions].
AB  - The data on growth and development of hind limb bones in chicken embryos under
      normal (standard) and altered incubation conditions are presented.

PMID- 18634337
TI  - [Peter Holland, homeobox genes, and the developmental basis of animal diversity].
AB  - In 1867 Alexander Kowalevsky published an account of the development of the
      cephalochordate Amphioxus lanceolatus (now known as Branchiostoma lanceolatum)
      (Kowalevsky, 1867). Together with his study of the development of urochordates
      (Kowalevsky, 1866; 1871), this introduced a new way of thinking about the
      relationship between the evolution and development of animals, and established
      the basis for longstanding theories of the evolutionary origin of vertebrates.
      Some one hundred and fifty years later, cephalochordates and urochordates are
      again in the spotlight, as molecular biology and genome sequencing promise
      further revelations about the origin of vertebrates. The work of the 2006
      Kowalevsky Medal winner, Peter Holland (Fig. 1), has played a central role in
      their reinstatement (see Mikhailov and Gilbert (2002) for more details of the
      history of the Kowalevsky Medal). Here, I profile Peter Holland's contribution to
      the rebirth of Evolutionary Developmental Biology in general and the study of
      homeobox genes and vertebrate origins in particular.

PMID- 18634339
TI  - [The prevalence of tetracycline resistance genes in clinical and commensal
      strains of Enterococcus faecalis isolated in Gdansk].
AB  - The common use of antibiotics is responsible for selecting of drug resistance not
      only in pathogenic, clinical bacteria but also in commensal, not pathogenic
      strains which could cause the rapid dissemination of the resistance to these
      antibacterial agents. However, information regarding the antibiotic resistance of
      commensal bacteria is very scarce, and the data is based mostly on phenotypical
      research. Therefore the use of genotyping methods for detection of tetracycline
      resistance genes, in commensal and medical isolates of bacteria, is essential,
      for understanding the spread of antibiotic resistance. In this study 24 commensal
      and 27 clinical isolates of Enterococcus faecalis has been screened by PCR
      methods for tet(M), tet(S) genes and Tn916 and Tn5397 transpozons. Subsequently,
      the tet(M) gene amplicones were sequenced and phylogenetic analysis was
      performed. We have found that the prevalence of tet(S) gene varied significantly
      between commensal and clinical strains. Moreover, the frequency of transpozons in
      clinical isolates was much higher comparing to strains isolated from healthy
      individuals. The phylogenetic analysis did not show significant differences
      between clinical and commensal strains but it could suggest that the genetic
      similarity between these two groups could be favourable factor for broad range
      spread of tet(M) gene.

PMID- 18634340
TI  - [Susceptibility to antimicrobial agents and genotypic relatedness of enterococcal
      strains isolated from patients and hospital environment].
AB  - The aim of this study was to evaluate antibiotic susceptibility of Enterococcus
      sp. strains isolated from two hospitals in lodz, during 2005-2006. The second
      goal was to determine possible transmission of these strains within hospital
      wards by using melting profile PCR. Enterococcal strains were identified to
      species according standard microbiological methods. There was isolated 159
      strains of E. faecalis, 51 strains of E. faecium and two E. avium, 1 E. durans.
      Susceptibility to antimicrobial agents was tested by disc diffusion method. None
      of these strains was resistant to vancomycin, teicoplanin or linezolid. There was
      high percentage of strains resistant to aminoglicosides, 22% of E. faecalis
      strains, and 54.9% of E. faecium strains, respectively. Additionally it was shown
      that 11.7% of E. faecium is resistant to chinuprisin-dalfopristin. The strains
      with similar pattern of resistance to antibiotics and fenotypic characteristics
      were genotyped by mpPCR. This technique was useful to confirm relatedness of
      bacterial strains suspected of being spread within hospital wards.

PMID- 18634338
TI  - [Increasing Streptococcus agalactiae colonization of pregnant women and newborns
      in south-eastern region of Poland].
AB  - Streptococcus agalactiae, group B streptococci (GBS) are a constituent of normal
      vaginal bacterial microflora which often do not give any clinical symptoms. On
      the other hand, during pregnancy there are optimal conditions for GBS
      multiplication in the vagina, which may have very serious consequences for both
      the mother and her child. The women (n = 563) that participated in our study were
      in their 3rd trimester and they were divided into groups: normal pregnancy or
      high risk pregnancy. We also examined their newborns. GBS identification was done
      basing on traditional culture method and its modification recommended by the CDC.
      We showed a slightly improved (about 4%) effectiveness of GBS detection in
      pregnant women using the CDC method. In high risk pregnancy GBS colonization was
      20% (among them 35% newborns were colonized) and in normal pregnancy it was found
      to be 17.2% (among them 26.7% newborns were colonized). Both in the high risk
      group and their newborns we confirmed a higher and statistically significant
      frequency of detection of GBS strains which had MLS(B) mechanism of antibiotic
      resistance. In newborns we confirmed two cases which were fatal. The results of
      our study show the need and necessity for implementing unified procedures
      recommended by the CDC in Poland.

PMID- 18634341
TI  - [Humoral response to selected antigens of Yersinia enterocolitica and Yersinia
      pseudotuberculosis in the course of yersiniosis in humans. IV. Specificity of
      antigens].
AB  - The specificity of the lipopolisacharydes and released proteins (Yop) of Yersinia
      was tested using the sera of rabbits immunised with pathogenic and non-pathogenic
      strain of Y. enterocolitica and Y. pseudotuberculosis as well as selected sera of
      patients. The results of this study showed a cross-reactions between the
      different serotypes of Y. enterocolitica with the strongest reactions between the
      pathogenic serotypes O:3 and O:9 and pathogenic serotype O:5,27 and non
      pathogenic serotype O:5. Sera positive for B. burgdorferi and from patients with
      Graves' disease showed a slight cross-reactivity with Yop proteins of Yersinia.
      However, the higher cross-reactivity was observed between the LPS of Yersinia and
      Salmonella spp. Due to the evidence of cross-reactivity the results of
      serological investigations should be interpreted with caution.

PMID- 18634343
TI  - [Hydrophobic and hemagglutinating properties of Klebsiella pneumoniae and
      Klebsiella oxytoca].
AB  - The aim of this study was to estimated hydrophobic and hemnagglutinating
      properties of Klebsiella pneumoniae and Klebsiella oxytoca rods. The
      hydrophobcity was evaluated according to the method of Rosenberg et al. The
      hemagglutinating properties were estimated by method of Blanco et al. Forty seven
      hydrophobic Klebsiella strains (30 K. pneumoniae strains and 17 K. oxytoca
      strains) were detected. Hemagglutinating properties were observed in 65
      Klebsiella strains (45 K. pneumoniae strains and 20 K. oxytoca strains).
      Hemagglutination of sheep tannined erythrocytes the most frequently was observed.
      Inhibition of hemagglutination of erythrocytes by K. pneumoniae strains was most
      frequently observed in presence of D-glucose and D-mannose and by K. oxytoca
      strains in presence of D-glucose.

PMID- 18634342
TI  - [ESBL-positive and ESBL-negative Klebsiella pneumoniae and Klebsiella oxytoca
      strains--occurrence in clinical specimens and susceptibility to selected
      antibiotics].
AB  - The aim of this study was to evaluated susceptibility to selected antibiotics and
      occurrence in clinical materials ESBL-positive and ESBL-negative K. pneumoniae
      and K. oxytoca strains. The susceptibility to selected antibiotics were tested by
      disk-diffusion method. None of the analysed strains was resistant to imipenem.
      Among non beta-lactam antibiotics thwe most strains were susceptible to
      fluoroquinolones. The most frequently K. pneumoniae strains were isolated from
      urine, K. oxytoca trains were isolated from wounds.

PMID- 18634344
TI  - [Assessment of the susceptibility of the gram-negative rods isolated from
      hospitalized patients to cefoperazone/sulbactam].
AB  - The susceptibility to cefoperazone/sulbactam of 197 strains of Gram-negative rods
      demonstrating an ESBL-positive phenotype was determined. The assortment of the
      investigated strains was as follows (numbers of strains are given in the
      brackets): E. cloacae (63), S. marcescens (46), K. pneumoniae (21), P. mirabilis
      (17), E. coli (9), P. vulgaris (8), P. aeruginosa (20) and A. baumanni (13). 83
      strains from 197 were susceptible (42.1%). The MIC values were determined and the
      disc-diffusion method was performed. The susceptibilities among particular
      species were as follows (the order of data in the brackets is: % of the
      susceptible strains/MIC50/MIC90): E. cloacae (54.0/16/64), S. marcescens
      (23.9/64/> or = 128), K. pneumoniae (38.1/32/64), P. mirabilis (41.2/32/64), E.
      coli (44.4/32/32), P. vulgaris (75.0/8/32), P. aeruginosa (35.0/32/64), A.
      baumannii (46.2/32/64). Using disc-diffusion method, for 184 strains the
      difference between diameter of the inhibition zone around the disc with
      cefoperazone and the disc with cefoperazone/sulbactam was calculated. This
      difference amounted 5 mm or more in the case of 76.6% of the investigated
      strains. The results indicate that the comparison of the inhibition zones around
      cefoperazone and cefoperazone/sulbactam discs may be an additional method useful
      for phenotypic detection of ESBL producing organisms. These results highly
      correlated with results obtained by using analogous test with cefpirome and
      cefpirome/clavulanic acid (85.6% of concordance).

PMID- 18634345
TI  - [Campylobacter jejuni infection in patient with Guillain-Barre syndrome: a case
      report].
AB  - The Guillain-Barre syndrome is an acute inflammatory polineuropathy; it's
      frequency is established at the level of 1,3 cases/ 100 000 persons/ year. The
      main etiological factors concerned with the GBS occurrence are: Campylobacter
      jejuni, cytomegalovirus, Epstein-Barre virus, Mycoplasma pneumoniae. The authors
      present a case of the 15 years old boy with the clinical features of acute motor
      axonal polineuropathy and confirmed C. jejuni infection. Identification of C.
      jejuni isolate was based on colony morphology on CCDA plate (OXOID),
      characteristic motility, catalase, oxidase, hippurate hydrolysis and acetate
      hydrolysis. The identity of C. jejuni was also confirmed by a specific PCR.
      According to the authors' knowledge this is the first case of a patient with GBS
      with confirmed C. jejuni infection reported from Poland.

PMID- 18634346
TI  - [Evaluation of blood cultures of children hospitalized in Upper Silesian Health
      Center of Child and Mother in Katowice].
AB  - Blood cultures (1613) taken from children hospitalized in 13 wards of Upper
      Silesian Health Center of Child and Mother were studied using Bact/Alert 240
      monitoring system (bioMerieux). Around 17.7% of studied cultures were positive:
      285 microorganisms were isolated. Gram-positive cocci dominated: 32.3% were
      strains of MRCNS Gram-negative rods, mainlyEnterobacteriaceae were isolated in
      18.6% of cases, non-fermenters--in 12.9%, yeasts (mainly C. albicans)--in 10.5%.
      More frequently blood cultures were positive in Intensive Care Unit (37.5%).

PMID- 18634347
TI  - [Anaerobic bacteria of periodontal pockets in course of periodontitis and
      premature labor].
AB  - The aim of the study is was to evaluate anaerobic periodontal mikrobes in 120
      postpartum mothers. Group I consisted of mothers with a birth weight of less than
      2,500g and gestational age < 37 weeks. Group II included mothers with normal
      birth weight infants. All women in both of groups were subjected to a full-mouth
      periodontal examination to determine a periodontal status. The microbial
      investigation for anaerobic bacteria of deepest periodontal pockets was performed
      in 35 cases of periodontits. A significantly higher incidence of preterm low
      birth weight cases in patiens with periodontitis was documented. In addition
      higher variety of anaerobic bacteria of periodontal pockets in mothers with
      preterm low birth weight infants comparison to control group was observed.

PMID- 18634348
TI  - Comparison of two approaches for calculation of the geometric and inertial
      characteristics of the human body of the Bulgarian population.
AB  - On the basis of a representative anthropological investigation of 5290
      individuals (2435 males and 2855 females) of the Bulgarian population at the age
      of 30-40 years (Yordanov et al. [1]) we proposed a 3D biomechanical model of
      human body of the average Bulgarian male and female and compared two different
      possible approaches to calculate analytically and to evaluate numerically the
      corresponding geometric and inertial characteristics of all the segments of the
      body. In the framework of the first approach, we calculated the positions of the
      centres of mass of the segments of human body as well as their inertial
      characteristics merely by using the initial original anthropometrical data, while
      in the second approach we adjusted the data by using the method based on
      regression equations. Wherever possible, we presented a comparison of our data
      with those available in the literature on other Caucasians and determined in
      which cases the use of which approach is more reliable.

PMID- 18634349
TI  - Kinematical analysis of mandibular motion in a sagittal plane.
AB  - The paper presents a kinematical model enabling the analysis of mandibular motion
      in a sagittal plane. Based on the recorded trajectories of incisors, the
      configuration coordinates were identified. The configuration coordinates
      explicitly identify the position and orientation of the mandible during motion.
      Such values are basic to the evaluation of alteration in muscle length and to the
      orientation of forces in particular muscles. This paper also deals with the
      influence of the coefficients of the weight matrix on the character of the
      solutions of the configuration coordinates applied in the model study of the
      kinematical chain. The results of the numerical calculations obtained
      demonstrated that the trajectory representation was in a considerable concordance
      with the data recorded.

PMID- 18634350
TI  - Fracture properties of an acrylic bone cement.
AB  - This study investigated experimentally the fracture properties, i.e., the fatigue
      strength, the resistance to crack propagation and the fracture toughness, of an
      acrylic bone cement (Cemex RX). The mean endurance limit was determined following
      the staircase method. The endurance limit was estimated at 9.2 MPa. The fatigue
      crack propagation rate was measured according to the ASTM E647 standard. The
      equation of the line fitting the crack growth per cycle (da/dN) versus the stress
      intensity factor range (delta K), in a log-log graph, was used to calculate the
      empirical constants of Paris' law for the selected bone cement: da/dN (m/cycle) =
      3.56 x 10(-7) x delta K (MPa x m1/2)5.79. This power-law relationship described
      well (R2 = 0.96) the growth rate in the stable crack growth region, i.e., in the
      mid delta K range. The fracture toughness K(IC) of the bone cement was determined
      according to the ASTM E399 standard. The K(IC) mean value was 1.38 MPa x m1/2.
      These experimental results provide the set of necessary inputs for numerical
      studies aimed to investigate the damage accumulation process in the mantle fixing
      cemented prostheses.

PMID- 18634351
TI  - Effect of silica precursors-type on mechanical properties of sol-gel coatings.
AB  - Reversion to narrowing, called restenosis, still remains an important problem of
      coronary angioplasty. Analysis of the problem revealed that the application of
      surface layers aimed at creating on the stent surface a neutral barrier between
      its metallic framework and tissues of the blood-vascular system is decidedly best
      to impede the restenosis. They also play the role of medicine carriers. This
      article presents a new sol-gel technology, to be applied in coronary stent
      coatings. Currently, this is one of the most progressive methods allowing the
      modification of surface layers of metallic biomaterials. The results presented
      prove that due to a proper selection of silica precursors it is possible to
      obtain continuous, smooth, plastic deformation-resistant sol-gel coatings, which
      additionally are characterised by very close adherence to the base material,
      nanometer thickness and low degree of surface development.

PMID- 18634352
TI  - Gait characteristics following Achilles tendon elongation: the foot rocker
      perspective.
AB  - The action of three functional rockers, namely the heel, ankle and forefoot
      rocker, assist the progression of the leg over the supporting foot. The purpose
      of this case series was to analyze the occurrence of foot rockers during gait in
      three children with cerebral palsy (CP) who had undergone the tendo-Achilles
      lengthening (TAL), procedure followed by a clinic- or home-based intervention and
      in one child with CP without history of surgery. Self-selected gait was video
      recorded in a laboratory during six testing sessions at half-year intervals
      rendering a 3 year period of observation. One child had pre- and post-surgical
      gait data and the other two had post surgical data only. Sagittal plane knee
      angular velocity, as well as foot to ground positions, and foot rocker occurrence
      were analyzed. In a child with history of CP, and without history of surgery,
      mean angular velocities of the 1st, 2nd and 3rd foot rocker were 3.7, 0.57 and
      6.67 rad/s, respectively, and the step length and cadence were normal. In
      children who underwent TAL the 1st and 2nd rocker was absent, as the initial
      contact of the foot with the ground was either with foot-flat or forefoot. The
      mean velocity of the 3rd rocker in children who underwent TAL was lower by
      approximately 50-80% than that of the nonsurgical case. Furthermore, the
      characteristic pattern of the knee joint to foot-floor position during gait was
      not observed in these cases. Foot rocker analysis identified children with
      abnormal gait characteristics. Following surgery these gait characteristics
      remained abnormal.

PMID- 18634356
TI  - [Ambulatory peritoneal dialysis--benefits, limitations and hopes].
AB  - Benefits and limitations of peritoneal dialysis as the first modality of
      integrated renal care are presented and supported by own clinical experience.
      Special attention was paid to the medical as well as non medical factors
      responsible for declining utilization of peritoneal dialysis as the only one form
      of home dialysis in Poland. Especially, promotion of new programmes supporting
      home dialysis assisted by qualified medical personnel was underlined.

PMID- 18634355
TI  - Properties of calcium carbonate-containing composite scaffolds.
AB  - Bone grafting in skeletal reconstruction has become a common task of orthopedic
      surgeon. Three-dimensional, porous, degradable scaffolds are often used to
      provide support while the new tissue can be formed in situ. There are numerous
      materials and techniques involved; however, each has certain drawbacks. One of
      the patented ceramic bone grafts is made of coral that has many benefits, e.g.,
      its chemical and surface structure similar to that of the cancellous bone,
      extremely good biocompatibility and optimal pore-size. The drawback, being
      difficult to overcome, is the manufacturing to the desired shape. In order to
      maintain the advantageous chemical composition, but to overcome these
      difficulties, we have manufactured polymer-ceramic scaffolds both by solvent
      casting and by melt mixing and particulate leaching. The scaffold morphology was
      examined using scanning electron microscope (SEM), while the compressive
      properties were chosen to validate these substrates mechanically.

PMID- 18634353
TI  - The biomechanical analysis of the traumatic cervical spinal cord injury using
      finite element approach.
AB  - According to up-to-date knowledge only mathematical modelling of the spinal cord
      injury (SCI) may provide real insight into a spatial location of the fields of
      the spinal cord mechanical strain generated by the injury. The purpose of our
      research was to correlate the results of Finite Element Analysis of SCI with the
      patient's neurological state and the injured spinal cord MR imaging. The 3D
      Finite Element Model of the cervical spinal cord and vertebral canal of a 21-year
      old male patient was created. The moment of the injury was reconstructed by a
      simulation of the displacement of nonelastic structure to the light of vertebral
      canal. A detailed spatial analysis of the stress, strain and dislocation
      distribution was performed. The most injured region was the superficial zone of
      the white matter, the anterior part and central region of the grey matter, which
      was in good agreement with patient's neurological staus. An individualized Finite
      Element Model of traumatic SCI constructed by us enabled the evaluation of the
      influence of mechanical strain on a neurological condition of a patient. Further
      research will consist in validation of the results of endurance analyses based on
      a enlarged group of patients.

PMID- 18634354
TI  - A novel total knee replacement by rolling articulating surfaces. In vivo
      functional measurements and tests.
AB  - The purposes of the paper were as follows: to show the fundamental functional
      differences between the natural knee and common total knee replacements (TKR), to
      describe the ideas on how main properties of the natural knee can be adopted by a
      novel TKR and to present some main biomechanical functions of this TKR. By
      analyzing the morphology of the articulating surfaces and the kinematics of the
      natural knee the design of the novel TKR was developed. The use was made of the
      test procedures established in vitro and of lateral X-ray photographs as well as
      fluoroscopy in vivo. The function of the novel TKR is comparable to that of the
      natural knee joint in terms of kinematics (roll/slide behaviour), loads of the
      articulating surfaces (diminished shear loads), stability and leeway under
      external impacts, reduction of the load in the patellofemoral joint, and ligament
      balancing.

PMID- 18634357
TI  - [Influence of controlled hypotensive therapy on renal autoregulation efficiency
      in the doppler captopril test in patients with chronic glomerulonephritis].
AB  - Regulation of renal vascular resistance is one of main mechanisms of the renal
      autoregulation. Renal vascular resistance is expressed in the Doppler sonography
      as a resistance index (RI). AIM OF THE STUDY: Estimation of renal resistance
      index variability in the Doppler Captopril Test in patients with chronic
      glomerulonephritis and hypertension in the course of controlled hypotensive
      therapy. MATERIAL AND METHODS: 21 patients (13 men + 8 female, age 40 +/- 14.5
      years) with chronic glomerulonephritis and hypertension were enrolled to the
      study. Twice, in about 6 months period of intensive hypotensive treatment, the
      Doppler Captopril Test was performed and variability of RI (deltaRI) was
      estimated. RESULTS: Significant rise of deltaRI 0.11 (-11.86:2.83) vs 1.15 (
      3.86:7.11); p < 0.05 was found, after 5.8 +/- 2.4 months of hypotensive therapy,
      and by preserved renal function. CONCLUSIONS: Controlled hypotensive therapy
      significantly improves efficiency of renal vascular autoregulation expressed as
      the variability of renal resistance index in the Doppler Captopril Test.

PMID- 18634358
TI  - [Role of nitric oxide system in pathogenesis of experimental model of hepatorenal
      syndrome].
AB  - Hepatorenal syndrome (HRS) is still one of a few great secrets of today's
      medicine. Pathomechanism of this syndrome, specially in case of an acute liver
      damage, is still poorly understood. AIM OF THE STUDY: In our study in
      experimental galactosamine (Ga1N) model, using the nitric oxide synthase (NOS)
      inhibitor- N omega-nitro-L-Arginine (L-NAME), we tried to explain, whether the
      nitric oxide plays some role in this model of HRS. MATERIAL AND METHODS: We used
      56 male Sprague-Dawley rats (SDR) divided into 7 groups. To achieve acute renal
      failure in all tested groups of animals GalN was given intraperitoneally. To
      determine influence of nitric oxide inhibition, L-NAME was given before and after
      Ga1N injection. Control groups received adequate volume of 0.9% saline solution.
      RESULTS: Liver and renal failure developed in all tested groups. Inhibition of
      NOS significantly but dose independently prevented the development of acute renal
      failure both before and after Ga1N injection. Pretreatment with L-NAME was
      significantly more succesful than post Ga1N treatment. CONCLUSION: Our study
      showed that inhibition of nitric oxide synthase prevents the development of renal
      failure in animal model of HRS. This is probably the first observation that
      nitric oxide plays important role in this model of HRS.

PMID- 18634360
TI  - [Cinacalcet in the therapy of secondary hyperparathyroidism--own experiences].
AB  - Secondary hyperparathyroidism (sHPT) affects 20-25% dialysed patients and is
      related to the bone, mineral and cardiovascular complications. Cinacalcet, acts
      on the calcium-sensing receptor increasing its sensitivity to calcium, thereby
      reducing parathyroid hormone (PTH) secretion. The aim of this study was to
      evaluate the effect of cinacalcet in dialysed patients with sHPT Material and
      methods. We studied group of 12 patients on dialysis > 3 month with sHPT and
      baseline iPTH > 450 pg/ml (F = 6, M = 6; peritoneal dialysis 2 patients and HD 10
      patients; mean age 56 +/- 14). Cinacalcet was titrated from 30 mg once daily
      during a 6 month period. The following parameters were determined in serum: iPTH,
      Ca, P, before onset of therapy and every 4 weeks during 6 months therapy.
      RESULTS: Serum iPTH significantly decreased after 4 weeks therapy compared to the
      start point (from 849 +/- 253 to 338 +/- 260 pg/ml) and after 24 weeks cinacalcet
      therapy to 298 +/- 153 pg/ml. (64% reduction). Serum calcium and phosphate
      decrease but not significantly 8.7 +/- 1.2 vs 8.6 +/- 1.1 mg/dl and 7.3 +/- 2.8
      vs 6.3 +/- 1.7 mg/dl respectively. There weren't serious adverse events.
      CONCLUSIONS: Cinacalcet is effective and well tolerated nonsurgical management
      treatment of secondary hyperparathyroidism in dialysed patients.

PMID- 18634359
TI  - [Race of experimental animals and development of renal failure in animal model of
      hepatorenal syndrome].
AB  - Hepatorenal syndrome (HRS) is still one of the most important challenges of
      medicine in 21st century. In spite of many years of experimental and clinical
      studies, it failed to discover precise pathomechanisms leading from hepatic
      damage to functional renal failure. Among many kinds and currents, experimental
      studies still play great role. There are few reported animal models of HRS, among
      them a rat model induced by galactosamine (GalN). In this model acute renal
      failure develops typically after hepatic damage. AIM OF THE STUDY: We tried to
      test, whether in this model different breeds might develop typical HRS in the
      same way. MATERIAL AND METHODS: We used 24 male Wistar and 16 Sprague-Dawley rats
      to achieve HRS by intraperitoneal injection of Ga1N. RESULTS. Liver failure with
      significant increase in serum concentration of bilirubin, alanine transaminase
      (ALT) and ammonia, as well as huge microscopic necrosis of hepatocytes developed
      in both groups, but we did not achieved any evidence of acute renal failure in
      Wistar rats group. Nevertheless, we found typical biochemical evidence of renal
      failure in Sprague-Dawley group. CONCLUSION: We conclude, that opposite to
      Sprague-Dawley model, the Wistar rat model does not develop functional renal
      failure typical for HRS, probably because of some congenital, genetic
      predispositions.

PMID- 18634361
TI  - [Cystatin C as a marker of glomerular filtration rate in patients with ovarian
      cancer].
AB  - Cystatin C, a cysteine protease inhibitor, has been recommended as a new marker
      of glomerular filtration rate (GFR). THE AIM OF STUDY We investigated
      significance of cystatin C in assessment of GFR and its influence on overall
      survival (OS) in patients with ovarian cancer (OC). MATERIAL AND METHODS: We
      prospectively included consecutive patients with OC, who after surgery were
      qualified to first line chemotherapy according to the following protocol:
      cisplatin 75 mg/m2 and 24-hour infusion of paclitaxel 135 mg/m2 every three
      weeks. We assessed: serum levels of creatinine (Cr), cystatin C (Cys C),
      creatinine clearance (ClCr) calculated from 24-hour urine collection, GFR
      estimated according to Cocroft-Gault (CG) and Modification Diet of Renal Disease
      (MDRD) formulas. RESULTS: Age median of 37 patients enrolled into this study was
      54 years (range from 28 to 68). We noted correlation between cystatin C and CrCl
      (R Spearman= -0.36; p = 0.03). We did not state any correlation between Cys C and
      another markers of GFR as: serum creatinine, CG, MDRD. However, we observed
      correlation between Cys C and measured tumor mass seeing in spiral CT-scan
      (diameter more than 1 cm) after surgery (R Spearman = 0.4; p = 0.01) and serum
      level of marker CA 125 (R Spearman= 0.4; p = 0.03). We didn't find any
      statistical correlation between values of serum Cys C (using median's as cutoff
      values) in overall survival of our patients (log-rank test, p = 0.9).
      CONCLUSIONS: Serum cystatin C level in patient with ovarian cancer is both the
      poor marker of GFR and has not prognostic value in the course of cancer after
      surgery with further primary chemotherapy. The explanation of this phenomenon
      could rely on the presence of residual ovarian cancer.

PMID- 18634362
TI  - [Treatment of renal anemia with intravenous erythropoietin in patients in the
      program of continuous ambulatory peritoneal dialysis].
AB  - AIM OF THE STUDY: In the face of non fully correctable renal anemia in patients
      on continuous ambulatory peritoneal dialysis (CAPD) injecting erythropoetin
      subcutaneously by themselves, we compared the effectiveness of renal anemia
      compensation as well as potentially positive influence on the clinical course of
      CAPD erythropoietin alpha (EPOalpha) given intravenously 1 or 2 times weekly, by
      PD-nurse at patients home with the same protocol of erythropoietin beta (EPObeta)
      given subcutaneously by patient himself or by family helper. MATERIAL AND
      METHODS: There were 2 groups of CAPD patients qualified in years 2003-2005 to the
      6 months study. Group 1 consisted of 12 patients who were receiving EPOalpha
      intravenously (7 women and 5 men; aged 57.8 +/- 14.0 years) and group 2 consisted
      of 12 patients who were given EPObeta subcutaneously by themselves (7 women and 5
      men; age 58.0 +/- 12.5 years). In the course of home visits the nurses supervised
      the correctness of CAPD program performed by patient or family helper. RESULTS:
      The results were as follows: we observed significant increase of the Hgb level in
      the group 1 between 3-rd and 6-th month of the study without significant increase
      of EPO dose. With respect to the course of CAPD program we found significantly
      higher frequency of peritonitis (1/11 vs 1/68 patient months; p < 0.05) and
      longer mean time of hospitalization (2.33 +/- 1.97 vs 1.17 +/- 1.03 days/pt; p <
      0.05) in the group 2 in comparison with group 1. Mean peritonitis-free survival
      time was significantly longer in the group 1 in comparison with the group 2
      (22.14 +/- 6.41 vs 16.51 +/- 9.70 weeks; p < 0.05). CONCLUSIONS: We conclude that
      EPOalpha given intravenously by PD-nurse in patient home enabled maintenance of
      recommended Hgb level. The additional benefit from nurse assisted PD was
      reduction of peritonitis rate as well as duration of hospitalization from various
      reasons.

PMID- 18634363
TI  - [Vascular access for hemodialysis--own experiences].
AB  - AIM OF THE STUDY: We present own experiences in creation and/or reconstruction of
      vascular access for hemodialysis. MATERIAL AND METHODS: 91 pts (63 men, 28
      female) aged 18 to 89 years, with irreversible renal failure qualified for renal
      replacement therapy, 47% of them with diabetic nephropathy. In years 1996-2006,
      167 surgical procedures of creation or reconstruction of vascular access for
      hemodialysis were performed. In the qualification for surgical procedure we used
      clinical assessment as well as Doppler ultrasound or computed tomography
      angiography. RESULTS: In 3 cases from all 167 patients we performed fistula
      ligation due to transfer to peritoneal dialysis. In the 164 others cases we
      performed 18 types of different procedures among other thing: 95 first or second
      degree arteriovenous fistulas creation, 35 procedures of revascularisation and 34
      procedures of fistula reconstruction. In our material own modification of Cimino
      Brescia arteriovenous anastomosis was introduced with positive hemodynamic
      effects in all cases. In the discussion we stressed the necessity of selection of
      creation/reconstruction methods individually for every patient especially in
      ageing and diabetic population of patients with chronic kidney disease with many
      cardiovascular complications both in predialysis stage of kidney failure as well
      as in the course of long term dialysotheraphy. CONCLUSION: The assurance in
      optimal vascular access for hemodialysis is still big challenge especially in
      patients of advanced age. Individual approach to every case gives the chance of
      choice the best surgical procedures for optimal vascular access for hemodialysis.

PMID- 18634364
TI  - [Severe nephrotic syndrome requiring bilateral renal arteries embolisation in
      patient with membranous and diabetic nephropathy].
AB  - On the case of 62 year old patient with diabetes type 2 complicated by diabetic
      nephropathy, we present diagnostic and therapeutic problems of severe nephrotic
      syndrome caused by membranous nephropathy confirmed by renal biopsy superimposed
      on diabetic nephropathy. Special attention was paid to the difficulties in
      achievement the remission of nephrotic syndrome with typical pharmacological
      treatment and necessity of using drastic form of treatment which was bilateral
      embolisation of renal arteries and subsequent continuous renal replacement
      therapy.

PMID- 18634365
TI  - [Asymptomatic intraperitoneal adhesions disease as the potential cause of
      unfeasibility of creation dialysis access to peritoneal cavity--case reports].
AB  - Peritoneal dialysis is one of three, complementary methods of renal replacement
      therapy, including also hemodialysis and kidney transplantation. After
      qualification for peritoneal dialysis program special attention should be paid
      for creation proper dialysis access through correct implantation of peritoneal
      catheter. On the basis of three cases we present difficulties of Tenckhoff
      peritoneal catheter implantation in patients with massive peritoneal adhesions
      without previous surgical interventions and other risk factors for peritoneal
      adhesions.

PMID- 18634366
TI  - [Nephrotic syndrome in the course of primitive neuroectodermal tumor--case
      report].
AB  - Case of Primitive Neuroectodermal Tumor (PNET) in a 47 years old woman with renal
      failure and nephrotic syndrome is presented. Few similar cases in adults reported
      in the literature with a variable, nonspecific clinical presentation and an
      aggressive course are discussed.

PMID- 18634367
TI  - [Translumbar cannulation of vena cava inferior as an alternative method of
      vascular access for hemodialysis].
AB  - The aim of our report is description of the first in Poland translumbar
      cannulation of vena cava inferior used as an alternative vascular access for
      hemodialysis in 62 years old patient without further access for hemodialysis and
      no access for peritoneal dialysis.

PMID- 18634368
TI  - [Schonlein-Henoch purpura--case report].
AB  - Schonlein-Henoch purpura is a systemic vasculitis characterised by purpura,
      joints and gastrointestinal involvement and glomerulonephritis. Organs injuries
      are associated with the deposition of immune complexes containing IgA in the wall
      of small vessels. This disease rarely affects adults. On the basis of the case of
      50 years old man clinical presentation, prognosis and treatment are presented.

PMID- 18634369
TI  - [Ambulatory or home peritoneal dialysis--time for changes?].
AB  - Ambulatory peritoneal dialysis need to be adopted to the changing population of
      patients with irreversible renal failure who require more and more nursing
      support in normal performance of dialysis procedure. Such possibility might be
      provided by introduction of supported or assisted by medical personal peritoneal
      dialysis in patient's home.

PMID- 18634370
TI  - [Advances in diagnosis and treatment of AL amyloidosis].
AB  - AL amyloidosis is a systemic disease characterized by extracellular amyloid
      deposition in tissues, causing progressive dysfunction of affected organs. The
      main clinical syndroms include nephrotic-range proteinuria with or without renal
      dysfunction, congestive heart failure, hepatomegaly and peripheral or autonomic
      neuropathy. The aim of therapy is the reduction of monoclonal light chains, by
      suppressing the underlying plasma cell dyscrasia. Recent therapeutic strategies
      involve intermediate-dose chemotherapy or high-dose melphalan supported by
      peripheral blood stem cell transplantation. Alternative therapeutic approaches
      include thalidomide, lenalidomide, iododoxorubicin, etanercept and rituximab.
      This paper reviews the pathogenesis, diagnosis and therapy of the AL amyloidosis,
      focusing on clinico-morphological symptoms of renal involvement, monitoring of
      treatment response and supportive therapy.

PMID- 18634371
TI  - [Clinical application of granulocyte concentrates in neutropenia caused by
      immunosupressive treatment].
AB  - Supplementary transfusions of granulocyte concentrates were known 70 years ago,
      when a direct relationship between decrease of the number of circulating
      granulocytes and the risk of sepsis was found. Using concentrates of granulocytes
      for treatment of severe bacterial and fungal infections in patients with
      prolonged neutropenia or disturbances of granulocytes function caused by
      immunosupression treatment is logically justified. Despite numerous clinical
      trials, the efficacy and safety of the concentrates transfusion still remains
      controversial. Early attempts were unsuccessful mainly because insufficient
      number of cells in concentrates. The technical progress enables now to achieve
      sufficient number of granulocytes for clinical purposes. Preliminary date suggest
      their clinical effectiveness. Further clinical studies on the role of granulocyte
      transfusions in the treatment of severe sepsis in patients with neutropenia or
      disturbances of granulocyte function caused by immunosupresion are needed.

PMID- 18634372
TI  - [Tartrate resistant acid phosphatase--TRACP-5b as a modern bone resorption
      marker].
AB  - The evaluation of bone metabolism in everyday practise is based on measurements
      of non-invasive bone markers. TRACP-5b has been considered as a potentially
      useful marker of bone resorption rate. It is an enzyme that is secreted by
      osteoclasts in the course of bone resorption. This review summarizes recent
      informations about TRACP 5b as a bone resorption marker in various clinical
      situations.

PMID- 18634373
TI  - [Glucose polymer in the long dwell exchanges in peritoneal dialysis--advantages
      and limitations].
AB  - The alternative dialysis solution containing glucose polymer- icodextrin was
      developed in response to disadvantages of conventional glucose solution such as
      metabolic disorders, structural changes in the mesothelium and glucose absorption
      from peritoneum leading to dissipation of the osmotic gradient and decrease of
      ultrafiltration. Icodextrin is especially indicated in patients with impaired
      ultrafiltration. In the paper current review of literature referred to the
      ultrafiltration effect of icodextrin in the long dwell exchanges was presented.

PMID- 18634374
TI  - [Peritoneal dialysis and insulin resistance in patients with chronic kidney
      disease due to nondiabetic nephropathy].
AB  - Significance of insulin resistance in patients with preserved renal function is
      currently well known. Disorders and clinical syndromes connected with insulin
      resistance in patients with chronic renal failure are broadly described in
      literature. Clinical significance of insulin resistance in patients with chronic
      renal failure treated with renal replacement therapy is still insufficiently
      explained and require more studies. Literature data indicate that long-term renal
      replacement treatment promotes development of insulin resistance. Furthermore it
      was proved, that insulin resistance in this group of patients is a strong
      independent predictor of mortality due to cardiovascular reasons. In patients
      treated with peritoneal dialysis, a potential risk factor of insulin resistance
      is persistent glucose overload, used as an osmotic agent in dialysis fluids.
      Insulin resistance as a potential agent of cardiovascular risk should be
      considered as a therapeutic target in patients undergoing peritoneal dialysis.

PMID- 18634375
TI  - [Biocompatibility of dialysis fluid in peritoneal dialysis--limitations and
      possibilities of improvement].
AB  - Standard glucose dialysis solutions are characterised by low biocompatibility
      because of hyperosmolality, low pH, lactate buffer and presence of glucose
      degradation products. These factors cause failure of peritoneum as dialysis
      membrane. In our paper we present problems of biocompatibility of glucose-based
      solutions as well as possibilities of improvement in this field thanks to
      application of alternative solutions.

PMID- 18634376
TI  - [Intradialytic hypotension].
AB  - Intradialytic hypotension is a frequent complication of hemodialysis. Its
      etiology is complicated and unclear. Preventive and therapeutic procedures
      include modification of lifestyle as well as parameters of hemodialysis
      procedure. Due to multifactorial etiology of this complication we should pay
      attention to proper prophylactic and in the case of its appearance to adjust the
      treatment to the individual patient.

PMID- 18634377
TI  - [Clinical value of the estimation of blood pressure circadian rhythm].
AB  - Arterial blood pressure is one of the main factors of the development of organ
      vascular changes. Clinical studies have demonstrated that not only blood pressure
      absolute values but its 24h profile as well may be of significance for the rate
      and severity of organ damage. The study analyses the results and observations of
      the so far carried out investigations concerning the lack of nocturnal fall of
      blood pressure on the development of vascular changes in brain, carotid artery,
      myocardial hypertrophy and renal lesions. The results of the study indicate that
      in subjects with the lack of nocturnal fall of blood pressure the frequency of
      organ changes is more pronounced. Thus, for normal monitoring of the course and
      the treatment of arterial hypertension, its 24h monitoring seems to be an
      indispensable procedure. When evaluating blood pressure 24h profile age, sex,
      organ changes, physical activity and real sleep-wake period should be taken into
      account. In hypertensive patients without organ changes with nondippers blood
      pressure profile, repetition of 24h blood pressure monitoring seems to be an
      indication.

PMID- 18634378
TI  - [The surgical dilation of glottic rima with laser surgery in paralysis
      dysphonia].
AB  - Vocal cord paralysis, a complication after strumectomy, affects about 1% of
      treated patients. Patients with unilateral paralysis are usually treated with
      foniatric and conservative therapy. Bilateral vocal cord paralysis with the
      paramedial placement of vocal folds usually requires surgical treatment.
      Trachoetomy is often done because of dyspnoe. The surgical procedures widening of
      glottis are performed in case no improvement after conservative therapy. MATERIAL
      AND METHOD: In 1989 Denis and Kashima first described the method of CO2 laser
      posterior cordectomy This method seems to be an effective and reliable surgical
      procedure. 36 patients with bilateral vocal cord paralysis underwent CO2 laser
      posterior cordectomy The follow-up period ranged from 6 to 36 months. All
      patients were decannulated by the third day after surgery. RESULT: The subjective
      evaluation of patients concerning treatment was satisfied. CONCLUSIONS: The
      operation resulted in significant improvement in the field of respiratory
      function of the larynx and a slight objective aggrevation in the quality of
      voice.

PMID- 18634379
TI  - [Comparison between two methods of inguinal hernia surgery--Lichtenstein and
      Desarda].
AB  - A preferable method of inguinal hernia repair nowadays is the use of mesh graft
      in tension-free techniques. In the past few years a new technique developed by a
      surgeon from India, Mohan P. Desarda, was introduced. This method is based on the
      use of an undetached strip of the external oblique aponeurosis which strengthens
      the posterior wall of the inguinal canal. The aim of this study was to compare
      the results of primary inguinal hernia repair in two groups of patients. One of
      the groups included the patients treated with Desarda technique (group I), and
      the second group included patients after Lichtenstein repair (group II). MATERIAL
      AND METHODS: In group I the questionnaires were sent to 58 patients, we received
      52 (89.6%) of them. In group II surveys were sent to 63 patients, we received 53
      (84.1%) of them. In order to unify the examined groups first fifty patients who
      filled up and sent back the questionnaires in each group were included in the
      study A group of patients after Desarda repair included 42 male and 8 female
      patients aged between 18 and 77 (average 48). The group II included 45 male and 5
      female patients aged between 24 and 89 (average 58). The surgery and
      hospitalization were analyzed, additional questionnaire was sent to individual
      patient six months after the hernia repair. Analysis of duration of surgery and
      hospitalization was performed, including the occurrence of complications during
      and after the surgery, patients' subjective evaluation of the surgery regarding
      pain and time of returning to normal physical activity, as well as hernia
      recurrence. RESULTS: Average duration of the Desarda repair was 56.6 minutes,
      while the Lichtenstein repair lasted for 66.5 minutes. After Desarda repair there
      was less intensive postoperative pain, rated in VAS scale at 3.3 in first day
      after the surgery, 2.1 in second day and 1.5 in third one, respectively in group
      II rated at 3.8, 2.7 and 1.6. Patients after Desarda repair were discharged from
      hospital on fourth day after the surgery, in group II on fifth postoperative day
      (p < 0.05). One week after the hemia repair patients in both groups equally
      classified the intensity of the pain (VAS 1.2). Six months after the
      hospitalization the effect of performed surgery was described as good or very
      good. Only one patient in group I was unsatisfied with the surgery results. There
      was minor intensity of the pain at this point--similar in both groups (I--0.8, II
      -1.1). Full activity was achieved by 46 patents in group I and 45 in group II.
      There was no hernia recurrence among the patients six months after the surgery.
      CONCLUSIONS: The Desarda and Lichtenstein methods of primary inguinal hernia
      repair do not differ in the means of procedure complexity and surgery time. The
      number of local complications and pain intensity were comparable and similar to
      the literature data. The patients after Desarda and Lichtenstein hernia repair
      were satisfied with the surgery results. Desarda primary hernia repair is as
      effective as Lichtenstein surgery and six months after the surgery the treatment
      results are similar in both groups.

PMID- 18634380
TI  - [Activity of superoxide dismutase (CuZn-SOD) in erythrocytes of patients after
      hips alloplasty].
AB  - Hip osteoarthritis leads, among others, to abnormally decreased physical activity
      (hypokinesia). Adverse effect of physical inactivity can cause inhibition of
      anabolic processes in favour of enhancement of protein, carbohydrate, and lipid
      catabolitic reactions, as well as inadequate metabolism of polyunsaturated fatty
      acids. These alterations can induce an increased lipid peroxide synthesis,
      overproduction of reactive oxygen species (ROS) and acceleration of lipid
      peroxidation processes. The aim of the study was to determine superoxide
      dismutase activity (CuZn-SOD) in red blood cells of patients suffering from hip
      osteoarthritis prior to and following total alloplasty as compared to healthy
      subjects, and also to evaluate effect of hypokinesia on oxidative stress.
      MATERIAL AND METHODS; CuZn-SOD activity in red blood cells was determined
      according to the Misra and Fridovich method in 36 patients with hip
      osteoarthritis hospitalized at the Traumatic-Orthopaedic Department of the
      Ministry of Internal Affairs and Administration Hospital in Lodz. RESULTS: In
      patients with decreased physical activity in ten days after alloplasty, enzyme
      activity increased (+24.9%), one month since the operation it decreased, but it
      higher as compared to result activity of CuZn-SOD prior to surgery (+16.8%).
      CONCLUSIONS: The results activity of superoxide dysmutase leads to ROS generation
      and their overgeneration in hip osteoarthritis and in first time of treatment.

PMID- 18634381
TI  - [The evaluation of costs of the abdominal aortic aneurysm endovascular
      treatment].
AB  - Abdominal aortic aneurysm (AAA) treatment by means of stentgraft implementation
      is a less post-operationally after-effected, way of treating the AAA on the
      contrast to the more traditional method. The aim of this study was to evaluate
      the costs of stentgraft implementation. MATERIAL AND METHODS: In the years 2001
      2006 65 patients were implemented the intervascular prosthesis. Only the patients
      with severe chronic medical problems were qualified for the treatment: 31 with
      the respiratory failure, 29 with the circulatory failure and 5 after the stroke
      with spastic hemiplegia. After CT of the abdominal cave and the angiography
      performed at the general anaesthetic the intervascular prosthesis was
      implemented. RESULTS: After the endovascular procedure was performed the
      complications could be noticed among 7 patients (10.76%), one patient died
      (1,53%). After obtaining the data from the Marketing Department the overall cost
      of treating the patients with endovascular prosthesis was 47500.39 PLN.
      CONCLUSION: Among patients with abdominal aortic aneurysm and with severe chronic
      medical problems costs of the endovascular prosthesis implementation are high,
      because costs of the stentgraft are high.

PMID- 18634382
TI  - [Disease acceptance in patients after surgery from breast cancer during
      supplementary treatment].
AB  - Breast cancer is the most frequent malignancy in women in Poland and all over the
      world. The etiology of this disease is unknown. It has a destructive influence on
      the internal world of each woman and releases negative emotions. Breast cancer
      causes disturbances in physical, psychological and social spheres of woman's
      life. The aim of the study was to assess the acceptance of the disease in women
      during supplementary therapy after mastectomy. MATERIAL AND METHODS: Twenty five
      women (32-70 years-old, median 53 years) were enrolled into the study. All
      patients were examined from 3 to 6 months after surgery and during supplementary
      therapy of breast cancer. The AIS scale was used for estimation of acceptance of
      the disease. It consists of eight questions describing consequences of bad health
      state and questions concern limitations imposed by the disease such as the lack
      of self-sufficiency, feeling of being dependent on other people and lowered self
      esteem. Each question included a five-grade scale. RESULTS: In the research group
      of 25 women those at age from 50 to 60 years were largest group and there were
      only few women from 30 to 40 years of age. 50% of women have no problems to adopt
      to the limitations imposed by the disease in the fifth and sixth month after
      surgery. 67% of women in the sixth month after surgery declared that they still
      did things they liked most despite their health state. The differences in the
      number of patients that could not do things they liked most were statistically
      insignificant in time. 80% of patients in the forth month after surgery felt
      absolutely useful. The differences in the number of women that felt useless were
      statistically insignificant in time. 67% of women in the third month as well as
      67% in the sixth month after surgery didn't claim to be more dependent on other
      people. 80% of patients in the forth month after surgery did not concern
      themselves as ones who burden to others. 100% of the analyzed patients felt
      absolutely useful during fourth months after surgery. 60% of women claimed to be
      self-sufficient in the forth month after surgery The biggest group of the women-
      75% in the fifth month after surgery had no feeling that people that spending
      time with them were embarrassed. The highest level of disease acceptance was
      observed in patients in the forth month after surgery while in the third, fifth
      and sixth months postoperatively and it was remained on a similar level. During
      supplementary breast cancer therapy the differences in disease acceptance in
      consecutive months after surgery were statistically insignificant. Most of the
      analyzed women--11 (44%) had good acceptance of the disease and bad acceptance of
      the disease had five patients (20%). CONCLUSIONS: Good acceptance of the disease
      during adjuvant breast cancer therapy after mastectomy had nearly half (44%) of
      the patients, the best acceptance in the forth month after surgery. More than
      half of the women felt useful and not more dependent on other people, they didn't
      feel to be a burden to others and they didn't feel to embarrass other people. The
      time that passed from surgery had no significant influence on the acceptance of
      the disease.

PMID- 18634383
TI  - [Lipodystrophy in HIV infected children].
AB  - The important side effect of antiretroviral treatment (ART) are metabolical
      disturbances and lipodystrophy. The consequences can be early atherosclerosis or
      ischemic heart disease. The aim of this study was to estimation of prevalence of
      lipodystrophy in HIV infected children on HAART risk factors and methods of its
      diagnosis. MATERIAL AND METHODS: Between 2002-2005 year 52 children (aged 3-18
      years) were included into study. There were 28 boys and 24 girls. An anamnesis
      was taken and physical examination was done every 6-12 weeks. Laboratory tests
      included: label of triglycerides, cholesterol with fractions, glucose. In 49
      patients body composition based on Bioelectrical Impedance Analysis (BIA) and in
      51 thicknesses of skin folds were measured. Patients were analyzed according to
      age, sex, Z score for Body Mass Index, clinical and immunological stage of HIV
      antiretroviral treatment (time, schemas, drugs) and its efficacy. RESULTS:
      Lipodystrophy was found in 24 (46%) children (12 girls and 12 boys), mean age
      9.68 years. Lipatrophy was recognized in 7, lipohipertrophy in 1 and the mixed
      form in 16 of cases. Children with lipodystrophy had complains much more
      frequently (96% vs. 64%) (p = 0.01). They had also thinner skin fold over/on the
      triceps (p = 0.02). Remaining skin folds were similar. Comparison of family
      history, age, sex, Z score for BMI, body composition based on BIA, clinical and
      immunological stage, efficacy of ART did not bring any significant statistical
      differences. All children with lipodystrophy were treated with D4T more
      frequently with DDI and RTV none of them received ZDV, rarely 3TC. Statistical
      differences were significant. In lipodystrophy group there were increased levels
      of triglicerydes much more frequently (79% vs. 39%) (p = 0.037). Remaining lipid
      abnormalities were also more frequent in that group, statistical differences were
      insignificant. CONCLUSIONS: 1. Lipodystrophy in observed group was very frequent.
      Clinical signs were recognized in 46%, hyperlipidemia in 73% of cases. Dominant
      was the mixed form. 2. The risk factor is treatment with D4T DDI, RTV. 3. The
      high risk of lipodystrophy in effective treated children changes opinion about
      therapeutical success and should require new therapeutical options. 4.
      Measurement of skin folds is useful method, but body composition based on BIA is
      not useful test for diagnosis of lipodystrophy.

PMID- 18634384
TI  - [Health hazards in Democratic Republic of Congo on the example of Polish soldiers
      in the stabilization mission EUFOR].
AB  - The aim of the study was to assess health hazards in Democratic Republic of Congo
      on the ground of diseases and traumas incidence among soldiers of Polish Military
      Contingent served in the stabilization mission EUFOR. MATERIAL AND METHODS:
      Epidemiological analysis was based on the medical documentation of patients
      treated from June to December 2006. RESULTS: The main health problem among Polish
      soldiers were gastrointestinal tract diseases (56,0% of all diseases and
      traumas), respiratory tract (22,9%) and skin diseases (7,4%). Among them acute
      diarrheas were dominated (they appeared in case of 98 soldiers in 126 examined
      population). The laboratory examination of homebound Polish soldiers showed
      pathological results in case of 81 people. Among them, 44 patients had certified
      the prevalence of Yersinia antibodies IgM--2 people, and IgG--42 people (Y
      enterocolica or Y pseudotuberculosis). Bacteriological examination of stool in
      direction of Yersinia spp. was negative. CONCLUSION: Laboratory examination of
      Yersinia antibodies before departure of Polish soldiers to Congo was not
      performed, so it is impossible to certify if infection of yersiniasis appeared in
      Poland or during military mission abroad. Among any homebound soldiers of Polish
      Military Contingent contagious or parasitic disease was recorded.

PMID- 18634385
TI  - [Estimation of protective effect of lipoic acid in the brain of rats during
      lipopolysaccharide-induced oxidative stress].
AB  - The aim of his study was to assess the effect of lipoic acid (LA) on
      concentration of protein in the homogenates of the cerebral cortex, the
      hypothalamus and the cerebellum in the early stage of oxidative stress. MATERIAL
      AND METHODS: Experiments were performed on male rats Wistar. The animals were
      divided into four groups consisting of eight animals each. Control group received
      saline alone into the tail vein (i.v.). The second group received LA (60 mg/kg
      b.w., iv.). The third group received only lipopolysaccharide (LPS) (30 mg/kg
      b.w., iv.). The fourth group received LPS (30 mg/kg b.w., iv.) and after 0.5 h
      received LA (60 mg/kg b.w., iv.). In the homogenates of the cerebral cortex, the
      hypothalamus and the cerebellum was measured concentration of protein by Lowry
      method. RESULTS: Treatment of LPS-injected rats with LA caused increase
      concentration of protein in the brain structures (p < 0.05). CONCLUSION: The
      early administration of LA a significant suppressed symptoms of oxidative stress
      induced LPS, expressed as a increase in concentration of protein in the study
      brain structures.

PMID- 18634386
TI  - [Double tachycardia. One heart with two arrhythmias. Difficulties in diagnosis
      and treatment with radiofrequency ablation--case report].
AB  - Double tachycardia (DT) is a coincidence of two arrhythmias. We described the
      coincidence of frequent and symptomatic premature ventricular contractions (PVCs)
      from the right ventricular outflow tract (RVOT) and atrioventricular nodal
      reentrant tachycardia (AVNRT). 54-years-old woman had no organic heart disease
      and 24 hours ECG Holter monitoring showed paroxysm of tachycardia and more than
      five thousands of PVCs. The patient was selected to invasive electrophysiology
      study (EPS) and radiofrequency (RF) ablation. The EPS confirmed induction of
      AVNRT and the presence of PVCs originating from RVOT The modification of slow
      pathway of AVNRT using RF ablation was performed. The ablation of PVCs was
      unsuccessful. After the ablation, ventricular arrhythmia remained symptomatic and
      patient underwent second session of RF ablation. With applications of RF current
      in RVOT only the reduction of PVCs was obtained but after 24 hours PVCs
      disappeared. During 12-month follow-up the patient remained free of any
      arrhythmias and palpitations.

PMID- 18634387
TI  - [Thoracic aorta dissection a difficult diagnostic problem at home--case reports].
AB  - Aortal dissection is one of the most life threatening complications of
      hypertension. The sudden, strong chest pain is leading symptom of disease, that
      is also frequent cause to call emergency. The aim of the study was to present
      diagnostic difficulties in case of aortic aneurysm dissection during giving aid
      by rescue team at home. RESULTS: There were described three evidence cases of
      aortic aneurysm dissection. The wide range of clinical symptoms as well as
      diagnostic difficulty in this state of threat of life was showed. The attention
      was turned on necessity of diagnostic procedures at hospital conditions. Chest
      computer tomography was performed to put proper diagnosis. The dramatic course
      and coincidence of other diseases makes it difficult for rescue team to introduce
      proper diagnosis and treatment at home. The introduced proceeding was limited to
      save transportation or required advanced live support before it. CONCLUSIONS: The
      recognition of aortic dissection is a very difficult task for emergency physician
      at scene. Patients, that present symptoms of acute dissection of thoracic aorta,
      should have quickly diagnosis and treatment at cardiology department.

PMID- 18634388
TI  - [Transient cortical blindness--a complication after coronary angiography--case
      report].
AB  - Transient cortical blindness is a very rare complication of cardiovascular and
      cerebral angiography procedures. We present a case of 63-years-old woman, who
      developed cortical blindness after coronary angiography. Computed tomography (CT)
      done immediately after blindness appearance showed bilateral hyperintensive areas
      (probably due to a leakage of contrast medium) in the occipital and parietal
      cerebral lobes. All visual symptoms disappeared during 48 hours and CT scan
      repeated after sight recovery did not show any focal lesions in the brain. A
      breakdown of the blood-brain barrier with direct contrast neurotoxicity seems to
      be the causal factor of neurological changes observed in our patient after
      coronary angiography.

PMID- 18634389
TI  - [Borreliosis--simultaneous Lyme carditis and psychiatric disorders--case report].
AB  - Borreliosis is a multisystemic disease transmitted by ticks. Its diagnosis still
      remains a challenge because of the varied clinical picture and of difficulties in
      detection of the etiological agent (Borrelia burgdorferi). We report a case of a
      53-years-old woman admitted to the Clinic of Cardiology due to life-threatening
      arhythmias with simultaneous deficits in concentration and memory. A suspicion of
      borreliosis was driven from the presence of cardiac symptoms as well as of
      psychiatric and from the case histories of a tick bite. The diagnosis was
      confirmed both by specific serological test and endomyocardial biopsy which
      revealed spirochetes. The patient responded to treatment with doxycyclin and
      ceftriaxone. Cardiologic disorders retreated entirely, while cognitive deficits
      did only partly.

PMID- 18634390
TI  - [Hyperlucent lung syndrom caused by pulmonary artery hypoplasia in patient with
      diagnosed asthma--case report].
AB  - We present case of 67-years-old, non-smoking woman with unilateral hyperlucent
      lung syndrome. She has diagnosed asthma and since 1997 she has been treated with
      inhaled corticosteroids and long-acting beta-agonists without improvement. She
      complained of a cough, shortness of breath, pulmonary function test reveal
      irrvesibility airflow obstruction. The routine X-ray chest showed unilateral
      hyperlucent left lung. Ct-angiography has shown unilateral hypoplasia of
      pulmonary artery. It indicates that in all cases of uncontrolled asthma should be
      considered another or coexisting diagnosis.

PMID- 18634391
TI  - [Langerhans' cell histiocytosis--diagnostic and treatment difficulties].
AB  - Langerhans' cell histiocytosis [(LCH), histiocytosis X] is a very rare disease,
      which can involve any side and organ of the body. LCH may appear as an isolated
      leasion or as a widespread systemic disease. Focus in the bone as eosinophilic
      granuloma can be separate or be involved only as a part of generalized disease.
      The aim of this study was describe diagnostic and treatment difficulties in two
      patients suffering from LCH. The first patient was 28-years-old man who had been
      treated by reason of tumor on the left angle of mandible in 2005 year. The second
      patient was a 2-years-old-child who had directed because of gomphiasis deciduous
      molar teeth in lower and upper jaws in 2005 year. After diagnosis child was
      treatment by chemotherapy and stay in remission. CONCLUSIONS: 1. In differential
      diagnosis of infiltrations and osteolytic losses of maxilla and mandible one
      should take into account LCH. 2. Differential localization and non characteristic
      symptoms can cause the late diagnosis and aggravate the prognosis of this severe
      disease. 3. Dentist in his practice should keep oncological vigilance because of
      the fact that he may be the first doctor for patients with LCH.

PMID- 18634392
TI  - [Atypical lymphocytes].
AB  - Atypical lymphocytes or reactive are cells that become large as a result of
      antigen stimulation. This cells usually are associated with viral illnesses,
      however they can also be present as result of drug reactions, immunisations,
      humoral diseases and auto-immune disorders.

PMID- 18634393
TI  - [Role of free radicals in the physiological processes].
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced
      during variety of biological processes. Low concentration of these molecules
      influences cell growth, differentiation or proliferation. Above derivatives of
      oxygen and nitrogen take part in physiological processes such as signal
      transduction, regulation of protein kinases or transcription factors. ROS and RNS
      regulate redox balance, regulate immune responses, activate macrophages and
      neutrophils. Under theirs' control is cell adhesion and relaxation of smooth
      muscles. These molecules are very important for correct function and life of the
      cell.

PMID- 18634394
TI  - [Nodular lymphoid hyperplasia--underestimated problem of gastrointestinal tract
      pathology in children].
AB  - Nodular lymphoid hyperplasia (NLH) is a rare condition with unknown etiology
      frequently associated with common variable immunodeficiency (CVID) and selective
      immunoglobulin A deficiency. NLH is a common cause of gastrointestinal bleeding.
      The risk of malignancy has been well recognized in subjects with NLH. The present
      knowledge about the nodular lymphoid hyperplasia (NLH) was described.

PMID- 18634395
TI  - [Neuroborreliosis--some aspects of pathogenesis, diagnosis and treatment].
AB  - Chosen pathophysiological aspects of Lyme borreliosis influencing on neurological
      symptoms, difficulties in diagnosis of neuroborreliosis and current opinions
      about effectivness of treatment. European recomendations--results of EUCALB
      expert group, AAN-American Academy Neurology supported some important studies
      connected with duration of therapy are described.

PMID- 18634396
TI  - [Factors influencing activity of oral anticoagulants. Interactions with drugs and
      food].
AB  - Oral anticoagulants (OAC) are commonly used as a life-long therapy in prevention
      of systemic embolism in patients with atrial fibrillation, valvular heart disease
      and prosthetic hart valves and in the primary and secondary prevention of venous
      thromboembolism. They are also used for the prevention of thromboembolic events
      in patients with acute myocardial infarction and with angina pectoris, in
      patients with biological hart valves and after some types of orthopaedics
      surgery. The International Normalized Ratio (INR) is used to evaluate the
      efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic
      complications increases when the INR is out of the therapeutic range. The aim of
      this study was to present information about the factors influencing activity of
      oral anticoagulants and interactions between oral anticoagulants and drugs or
      food. The effect of oral anticoagulants is influenced by genetic and
      environmental factors such as: medicines, food, diseases and pre-existing
      conditions. A common mutation in the gene coding for the cytochrome P450
      (CYP2C9), with one or more combinations of its polymorphisms, is responsible for
      the reduced warfarin requirements or for the resistance to warfarin. A mutation
      in the factor IX is responsible for the risk of bleeding during OAC therapy
      without excessive prolongation of the prothrombin time (PT). Drugs, herbs and
      multivitamin supplements can alter the absorption, pharmacokinetics or
      pharmakodynamics of OAC. Nonsteroid anti-inflammatory drugs and paracetamol in
      combination with OAC seem to be the most dangerous because they are available
      without prescription and are used without medical consultation. Patients on OAC
      therapy are sensitive to changing dietary intake of vitamin K, which is supplied
      from phylloquinones in plants or from vitamin K-containing medicines. The effect
      of OAC can be influenced by other existing factors like: fever, diarrhoea,
      alcohol abuse or physical hyperactivity. Some malignancies or other diseases like
      cardiac insufficiency, hyperthyroidism and hypothyroidism or hepatic dysfunction
      may also affect OAC therapy. This treatment requires patients and doctors to be
      knowledgeable about factors influencing the activity of oral anticoagulants. For
      this reason educational programme on OAC therapy should be conducted among
      patients and doctors.

PMID- 18634397
TI  - [Use of oral anticoagulants in outpatient setting].
AB  - Oral anticoagulants (OAC) have been used for more than 60 years and are being
      prescribed to a steadily increasing number of patients as a life-long therapy The
      Intenational Normalized Ratio (INR) is used to evaluate the efficacy of anti
      coagulant therapy. The risk of thromboembolic and haemorrhagic complications
      increases when the INR is above the therapeutic range. The aim of our study was
      to provide information about oral anticoagulant therapy and how to treat patients
      on OAC therapy in specific situations such as: pregnancy, intramuscular
      injection, tooth extraction and small invasive procedures performed in outpatient
      setting. INR needs to be frequently monitored during treatment and in many
      countries this is done in specialist anticoagulant clinics. Such clinics do not
      presently exist in Poland and patients on OAC treatment typically fall under the
      care of doctors of different specialization including general practitioners. OAC
      therapy is safe until fourth--sixth week of pregnancy, after his time
      anticoagulant treatment should be replaced by heparins. Intramuscular injections
      are contra-indicated during OAC therapy. In most cases general dental treatment
      and straightforward single dental extractions can be performed without
      discontinuing OAC, provided INR is in the therapeutic range of 2,0-3,5. Risk of
      bleeding can be minimized by the use of mouthwashes (used three or four times a
      day for 2 days) containing 4,8% tranexamid or 25% e-aminocapronicum acid. Prior
      to undergoing invasive procedures with a middle risk of bleeding and single
      extraction in patients with a risk of major bleeding should consult with a
      physician specializing in the use of anticoagulants to discuss the treatment and
      to assess the risk of bleeding and thromboembolism. This is why education about
      the therapeutic range of INR and procedures which need to be adopted in specific
      situations, is very important and the educational programme on OAC therapy should
      be targeted at patients and doctors of different specialization including general
      practitioners.

PMID- 18634398
TI  - [Endocrinal dysfunctions in liver failure of different etiologies and during
      interferon therapy in patients with chronic hepatitis B and C].
AB  - Liver failure is decadent stage of its severe damage, in which, processes of
      detoxication, carbohydrate and lipid metabolism, nitrogen balance and synthesis
      of high-energy compounds are significantly diminished or even totally blocked.
      Moreover, these incorrect metabolic pathways as well as oxygen deficiency in
      hepatocytes are implicated in the pathogenesis of endocrine system diseases. The
      different endocrinal dysfunctions make worse patient's prognosis.

PMID- 18634399
TI  - [Psychological aspects of overweight, obesity and dieting].
AB  - Overweight and obesity are global and increasing health problems which contribute
      to the development of number of serious diseases. Although knowledge of the
      biological aspects of overweight and obesity is increasing very rapidly,
      psychological factors associated with this problem have not been enough
      considered. It seems very important to work out psychological theory and research
      concerning emotional and cognitive aspects of being obese, to search for
      psychological causes of obesity and to implement psychological interventions
      which improve motivation for management and effectiveness of treatment of people
      with overweight and obesity. The aim of this article is to review current
      knowledge concerning psychological aspects of overweight and obesity.

PMID- 18634400
TI  - [Intrathecal baclofen therapy].

PMID- 18634401
TI  - [Microvascular decompression surgery for trigeminal neuralgia: technical review
      based on surgical anatomy].
AB  - To perform secure microvascular decompression for trigeminal neuralgia, it is
      important to perform each surgical procedure based on detailed anatomical
      knowledge. As for microsurgical procedure, there are two major approaches; the
      supracerebellar approach and the trans-horizontal fissure approach. This article
      reviews the advantages of each surgical approach and describes points to pay
      attention to, with figures which will help the surgeon to perform this surgery.
      The importance of real decompression or transposition of the offending vessels is
      stressed. The significance of preoperative imaging as well as perioperative
      management including the patients' positioning is also described.

PMID- 18634402
TI  - [A study of intraarterial pressure changing during cerebral angiography].
AB  - BACKGROUND: Elevation of cerebral blood pressure induced by injection of contrast
      medium has been postulated as a major cause of rerupture of cerebral aneurysms
      during angiography. The current study was performed to clarify whether intra
      arterial pressure elevation occurs during contrast injection. MATERIALS AND
      METHODS: The study included six patients. To confirm the accuracy of pressure
      measurement, a pressure wire (SmartWire) was used. The changes in intravascular
      pressure were measured by the pressure wire and through a microcatheter and a
      guiding catheter The data from these modalities were then compared. The contrast
      injection flow rate was 4 ml/s in ICAG (internal carotid angiography), 3 ml/s in
      VAG (vertebral angiography) and 5 ml/s in CAG (carotid angiography), and all
      injections were administered without contrast wedging, regurgitation or
      mechanical spasm in adjacent arteries. RESULTS: The pressure measured through the
      guiding catheter was the same as that measured with the pressure wire, but the
      data obtained through the microcatheter was not more than reference data. The
      changes in pressure were not evident in the distal end of the catheter tip.
      CONCLUSION: Intra-arterial pressure elevation probably doesn't occur under
      appropriate injection, resulting in safer cerebral angiography. However, in case
      a high contrast injection flow rate is required to produce a better image,
      surgeons should also be aware of the possibility of pressure elevation.

PMID- 18634403
TI  - [The influence on the images of computed tomography caused by the use of
      artificial cranial reconstructive materials].
AB  - Various materials have been used for cranioplasty; however, these materials
      frequently produce artifacts that appear when examined with conventional
      radiography. Computed tomography (CT), in particular, detects high density
      artifacts near artificial bones, which is manipulated by increased noise, and
      limits diagnostic performance. The purpose of this study was to evaluate the
      extent and shape of the artifacts due to artificial cranial bones and to consider
      CT imaging parameters necessary for accurate recognition of structures under the
      materials. Four different artificial bone materials were evaluated in this study:
      hydroxyapatite with 1) 40% or 2) 50% porosity, 3) titanium plate, and 4)
      hydroxyapatite-polymethylmethacrylate composite (HA-PMMA). CT scanning was
      performed with standard clinical settings. Sample specimens were placed on the
      right side, under the artificial bones, and CT was performed to evaluate specimen
      visibility. We compared the artifacts created by the four bone types listed
      above, and measured the CT values of those materials. With ordinary scan
      settings, all the artificial bones revealed high-density artifact surrounding the
      materials, including the inability to accurately measure specimen thickness. The
      upper part of the specimen in contact with the artificial bones could not be
      distinguished from the artifact. The CT value in the medial aspect of the
      artificial bones increased more than the actual CT values. Of the four artificial
      bone materials studied, HA-PMMA produced the fewest artifacts. Description of the
      structures under the artificial bones can be improved by extending the window
      width to approximately twice that of normal settings.

PMID- 18634404
TI  - [The management of patients with thoracic outlet syndrome (TOS) and an assistant
      diagnosis to discriminate between TOS and cervical spondylosis].
AB  - Between 1984 and 2007, 20 patients, admitted to our hospital for the treatment of
      thoracic outlet syndrome (TOS), were analyzed. Of these 20 patients, 2
      subsequently entered rehabilitation to strengthen the muscle power surrounding
      the shoulder, 5 were followed by a brachial plexus anesthesiological block for
      the purpose of both diagnosis and treatment of TOS, and the other 13 patients
      underwent a total of 18 surgeries. Surgical methods consisted of a
      supraclavicular first rib resection with anterior and middle scalenectomy (SCFR +
      AMS) in 16 surgeries, and a transaxillary first rib resection (TAFR) in 2
      surgeries. Preoperative symptoms disappeared immediately after surgery in all
      cases except for 1 that was treated by a TAFR. The surgical result of SCFR + AMS
      was favorable and effective to prevent a symptomatic recurrence due to the
      postoperative re-adhesion. We measured the inclination of the clavicle in these
      TOS patients, using a chest X-ray, which determines indirectly the width of the
      costoclavicular space, and compared it with that of 18 patients with cervical
      diseases, including cervical spondylosis and cervical disc herniation, who were
      operated on at our institution. By comparison of the inclination angle of the
      clavicle between the injured and the non-injured side in each diseases, it was
      shown that the injured side had declined by 3.0 degrees but than the non-injured
      side in TOS, more by only -0.1 degrees in the cervical diseases. This method may
      be utilized as an assistant diagnosis to discriminate between TOS and cervical
      diseases.

PMID- 18634405
TI  - [Spontaneous improvement of idiopathic intracranial carotid artery dissection: a
      case report].
AB  - We report a rare case of spontaneous intracranial carotid artery dissection
      presenting with multiple infarctions. A 65-year-old man became aware of transient
      visual disturbance in the right eye and headache. Magnetic resonance imaging
      (MRI) at a local neurosurgical clinic depicted fresh multiple infarctions of the
      right cerebral hemisphere along with severe right carotid artery stenosis and
      delayed cerebral blood flow on the right side. The patient was transferred to our
      hospital. Three-dimensional computed tomography (3D-CT) showed an intimal flap in
      the righ petrous internal carotid artery and we diagnosed spontaneous
      intracranial carotid artery dissection of the petrous portion. We started
      conservative therapy including anti-coagulant and antiplatelet drug and blood
      pressure control. Two weeks after admission, angiography, 3D-CT, MR angiography
      demonstrated that the dissection had improved and the patient was discharged
      without neurological deficit. In this case, 3D-CT was effective for the diagnosis
      of intracranial carotid artery dissection. We report this rare case along with a
      literature review of the clinical profile and related neuroimaging findings.

PMID- 18634406
TI  - [Infectious aneurysm rerupture caused by delayed diagnosis: an operative case
      report].
AB  - A 21-year-old febrile woman with sudden onset of headache and semicoma was
      transferred to our institute. CT and 3D-CT angiography showed subaracnoid
      hemorrhage and intracranial hemorrhage in the left hemisphere due to a saccular
      aneurysm at the occluded M2 portion of the middle cerebral artery (MCA). Her
      present illness started with a toothache and lumber pain 3 weeks earlier.
      Echocardiography revealed active infective endocarditis. We could have treated
      her by administering antibiotics, but during a cerebral angiography, she became
      comatose due to an aneurismal rerupture. Immediately, an emergency operation for
      aneurismal trapping was performed, but she died 19 days later because of left
      hemispheric swelling. We report a relatively rare case of infectious aneurysm at
      the proximal artery and discuss the pitfalls of its diagnosis and treatment. We
      should educate general physicians about infectious endocarditis because
      misdiagnosis or delayed diagnosis of infectious aneurysm due to endocarditis
      results in unpleasant outcomes. We should treat infectious aneurysm at the
      proximal side artery by first administering antibiotics, and if necessary,
      subsequent direct surgery of the aneurismal trapping should be performed with a
      bypass. Unnecessary invasive treatment must be avoided while the disease is in
      the active infectious stage.

PMID- 18634407
TI  - [A case of cerebrospinal fluid hypovolemia caused by Ommaya reservoir
      successfully treated by epidural blood patch].
AB  - Here, we report a case of cerebrospinal fluid hypovolemia caused by lumbar
      puncture for implantation of an Ommaya reservoir. A 55-year-old man with central
      nervous system lymphoma developed meningeal dissemination. He was treated by
      spinal radiotherapy, and had an Ommaya reservoir implanted for intrathecal
      injection of anticancer drugs. After one month, he complained of orthostatic neck
      pain. MRI revealed bilateral subdural effusion and diffuse meningeal enhancement.
      He was diagnosed as having cerebrospinal fluid hypovolemia. Because no
      improvement in symptoms was seen after 2 weeks of conservative treatment, he was
      treated by a lumbar epidural blood patch. Subsequently symptoms improved
      markedly, and bilateral subdural effusion and diffuse meningeal enhancement
      disappeared on follow-up MRI.

PMID- 18634408
TI  - [Multiple intracerebral enhanced lesions strongly suspected to be
      microsporidiosis. A case report].
AB  - This case of microsporidiosis manifested as mutiple intracranial lesions
      separated in space and time, and neurological and radiological findings were
      improved with albendazole administration. A 33-year-old man presented with
      headache, fever, and dysphasia. His consciousness was clear. Neurological
      examination revealed acalculia, agraphia, and homonymous hemianopsia. He had a
      past history of febrile convulsive seizures of unknown cause until 14-years-old,
      but no history of immunodeficiency. T1-weighted magnetic resonance (MR) imaging
      showed a hypointense lesion with a hyperintense part, and ring-like enhancement
      with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA), in the left
      temporal lobe. T2-weighted and diffusion-weighted MR imaging showed the lesion
      surrounded by moderate hyperintense areas. He underwent gross total resection of
      the lesion. Histological examination demonstrated intracellular clusters of small
      basophilic spore-like bodies in the astrocytes, suggestive of microsporidia
      infected astrocytes. However, immunohistochemical, polymerase chain reaction, and
      serological analyses failed to confirm the definitive diagnosis of
      microsporidiosis, so that he received no further treatment. Three years later, he
      presented with sensory disturbance in the left side of his face and left
      cerebellar ataxia, followed by fever, abnormal sensation in the left side of his
      face, and aggravated ataxia of the left upper and lower extremities on day 10
      after admission. T1-weighted MR imaging with Gd-DTPA showed an enhanced lesion
      with irregular margin in the left cerebellar peduncle. T2-weighted MR imaging
      showed a diffuse hyperintense region around the lesion. Cerebrospinal fluid
      culture, serological analysis for autoimmune disease, and thoracic, abdominal,
      and pelvic computed tomography and 18F-fluorodeoxyglucose-positron emission
      tomography detected no abnormalities such as cancers or other lesions in the
      extracranial organs. No definitive diagnosis was obtained, but recurrence of
      microsporidiosis was the most probable cause. Administration of albendazole (600
      mg/day) was started on day 15, because of rapid neurological and radiological
      deterioration. This treatment resulted in clinical improvement and disappearance
      of the lesion on MR imaging after daily administration for 4 weeks. He was
      discharged on foot with moderate sensory disturbance in the left side of the face
      and ataxia. Based on the clinical course and negative findings, the final
      diagnosis was microsporidiosis. This case suggests that microsporidiosis in the
      central nervous system can persist even in immunocompetent patients without
      involvement of any other organs, and that albendazole administration is likely to
      be effective.

PMID- 18634410
TI  - [Two-year-old boy with nystagmus and visual disturbance].

PMID- 18634411
TI  - [A novel proposal explaining sleep disturbance of children in Japan-
      asynchronization].
AB  - It has been reported that more than half of the children in Japan suffer from
      daytime sleepiness. In contrast, about one quarter of junior high-school students
      in Japan complain of insomnia. According to the International Classification of
      Sleep Disorders (Second edition), these children could be diagnosed as having
      behaviorally-induced insufficient sleep syndrome due to inadequate sleeping
      habits. Getting on adequate amount of sleep should solve such problems;however,
      such a therapeutic approach often fails. Although social factors are involved in
      these sleep disturbances, I feel that a novel notion - asynchronization - leads
      to an understanding of the pathophysiology of disturbances in these children.
      Further, it could contribute to resolve their problems. The essence of
      asynchronization is a disturbance of various aspects (e.g., cycle, amplitude,
      phase, and interrelationship) of the biological rhythms that normally exhibits
      circadian oscillation. The main cause of asynchronization is hypothesized to be
      the combination of light exposure during night and the lack of light exposure in
      the morning. Asynchronization results in the disturbance of variable systems.
      Thus, symptoms of asynchronization include disturbances of the autonomic nervous
      system (sleepiness, insomnia, disturbance of hormonal excretion, gastrointestinal
      problems, etc.) and higher brain function (disorientation, loss of sociality,
      loss of will or motivation, impaired alertness and performance, etc.).
      Neurological (attention deficit, aggression, impulsiveness, hyperactivity, etc.),
      psychiatric (depressive disorders, personality disorders, anxiety disorders,
      etc.) and somatic (tiredness, fatigue, etc.) disturbances could also be symptoms
      of asynchronization. At the initial phase of asynchronization, disturbances are
      functional and can be resolved relatively easily, such as by the establishment of
      a regular sleep-wakefulness cycle;however, without adequate intervention the
      disturbances could gradually worsen and become hard to resolve.

PMID- 18634412
TI  - [Study on discrepancy in perceptions of parents and teachers regarding children
      with developmental disorders].
AB  - Behavioral problems in children with developmental disorders might be recognized
      differently by parents and teachers. To assess this hypothesis, the same
      checklist created by authors was fulfilled by both parents and teachers of the
      same 45 children with developmental disorders. Most parents agreed that their
      children had problems on attention, while many teachers reported that these
      children had problems on hyperactivity and interpersonal communication.
      Acknowledging this discrepancy on the perception between parents and teachers is
      expected to be useful information for physicians to diagnose and support children
      with developmental disorders.

PMID- 18634413
TI  - [Seizure characteristics in Kawasaki disease].
AB  - It is well known that convulsions may occur in clinical course of Kawasaki
      disease. However, the features of such seizures remain unclear. Recent reports
      have hypothesized that proinflammatory cytokines may contribute to the genesis of
      febrile convulsions (FC). In the acute phase of Kawasaki disease, proinflammatory
      cytokines are elevated in serum and CSF. If cytokines play a role in seizure
      phenomena in patients with Kawasaki disease, FC and seizures in Kawasaki disease
      might share some clinical features. To clarify the clinical features of
      convulsion in Kawasaki disease, we investigated 7 patients with Kawasaki disease
      with convulsions who were diagnosed and treated from November 2003 to November
      2005. We found several features of the seizures, as well as the onset age, were
      diffrent among these clinical entities. The onset of Kawasaki disease was
      characteristically before six months of age in all patients. Seizure clustering
      was seen in 5 patients and partial seizures in 4. Prolonged unconsciousness after
      seizures was seen in one patient, syndrome of inappropriate secretion of ADH
      (SIADH) in one other. One patient had markedly elevated IL-6 in CSF. These
      observations led us to speculate that the convulsion of Kawasaki disease may be
      attributable to an encephalitis. The results of this study suggest that seizure
      pathophysiology differs between FC and Kawasaki disease.

PMID- 18634414
TI  - [Adaptation to elementary school and the effect of rehabilitation approach in
      children with high-functioning pervasive developmental disorders].
AB  - Adaptation to elementary school was investigated in 32 children with high
      functioning (IQ > or = 70) pervasive developmental disorders. Eight children who
      were diagnosed or supported before the entrance of elementary school adapted
      smoothly and enjoyed school life. However, the other 24 children had maladjusted
      problems in school;that is, 12 children refused to go to school or class (SR),
      and the other 12 children had behavioral problems (BP), such as violent behaviors
      or hyperkinesis. I tried to solve the problems through rehabilitation, in
      cooperation with occupational therapists and speech-language and hearing
      therapists. Ten of 12 children with SR could go to class and nine of 12 children
      with BP could resolve their behavioral problems after six months. It was
      important that parents and teachers could understand children's difficulties
      correctly and the condition of school environment. The lack of improvement in the
      remaining five children were due to severe autistic symptoms in three children
      and the refusal of family members to accept the child's disability in two.

PMID- 18634415
TI  - [Evaluation of preclinical onset in patients with the childhood form of cerebral
      adrenoleukodystrophy--usefulness of visual cognitive function and evoked
      potential tests].
AB  - We examined both visual evoked potential (VEP) and neuropsychological tests in 18
      patients with X-linked adrenoleukodystrophy (ALD). Patients consisted of 10 boys
      with apparent lesions in the posterior white matter on MR imaging, 3 with lesions
      in the frontal white matter area and 5 that were neurologically asymptomatic with
      no apparent brain MRI abnormalities. Almost all patients with posterior WM lesion
      showed patterns of lower PIQ than VIQ on WISC-III and lower scores on scales for
      simultaneous processing than for sequential processing on Kaufman Assesment
      Battery for Children (K-ABC). Four of 5 asymptomatic patients showed PIQ/VIQ
      patterns similar to those in the posterior group. Patients with a difference more
      than 13 between PIQ and VIQ also showed poor results on Frostig developmental
      test of visual perception (DTVP). There was a prolongation of the peak latency of
      P100 on flash VEP in many patients with posterior whitematter lesions, however,
      asymptomatic patients did not show any abnormality of P100 latency but there was
      an increased amplitude of N75-P100 on flash and pattern reversal stimuli VEP. One
      patient with abnormally high VEP (31.4 microV; + 3.6 SD) gradually improved to
      the normal range (11.4 microV; 0SD) after hematopoietic stem cell
      transplantation. These cognitive and neurophysiological examinations could be
      useful in the detection of preclinical onset of childhood ALD before the
      appearance of MRI lesions on MRI.

PMID- 18634416
TI  - [Application of the Bayley scales of infant development as a developmental test
      for Japanese infants with congenital heart disease].
AB  - The Bayley Scales of Infant Development 2nd edition (BSID-II) is used worldwide
      as a test for assessing development in infants with congenital heart disease
      (CHD); however, a Japanese version of these tests is not available. To introduce
      BSID-II in Japan, it was first used for 1-year-old Japanese infants with and
      without CHD (controls). The BSID-II scores of the control group were lower than
      American standards. In addition, the scores of the infants with CHD were lower
      than those of the controls, particularly the scores for motor development.
      Tsumori's Mental Development Test scores for the two groups were comparable;
      however, a diverse correlation was observed between BSID-II and Tsumori's Mental
      Development Test. No problems were encountered during the translation and use of
      BSID-II. These results suggest that BSID-II is useful for the assessment of
      development in Japanese infants.

PMID- 18634417
TI  - [Neuroradiological studies in Rett syndrome].
AB  - Rett syndrome is a neurodevelopmental disorder characterized by autistic behavior
      as well as cognitive and motor skill loss that occurs early in life and almost
      exclusively affects females. We studied the neuroradiological findings from MRI,
      SPECT, and proton magnetic resonance spectroscopy (1H-MRS) in 4 cases of Rett
      syndrome. Three of the 4 cases were diagnosed as Rett syndrome by gene analysis
      of MECP2. MRS demonstrated a decrease of N-acetylaspartate (NAA) in all 4 cases
      of Rett syndrome. In addition, MRI revealed frontal cortical atrophy and SPECT
      demonstrated low blood flow in the frontal lobe. We speculated that this decrease
      in NAA reflected neuronal loss, immaturity or hypofunction in these regions. The
      results of our study were in agreement with the previous studies on Rett syndrome
      by neuropathological methods.

PMID- 18634418
TI  - [A case of necrotizing tracheitis and tracheobronchomalacia in a patient with
      severe motor and intellectual disabilities].
AB  - We report a 23-year-old male patient with severe motor and intellectual
      disabilities due to sequelae of intracranial hemorrhage, who have had suffered
      from pneumonia with pleural effusion after influenza infection followed by
      mechanical ventilation. This patient also had complication of
      tracheobronchomalacia. Positive pressure ventilation in addition to
      thoracheocentesis was necessary for the drainage of pleural effusion. Abrupt
      hypooxygenation during mechanical ventilation revealed the presence of
      necrotizing tracheitis, which was improved with removal of necrotic tissues by
      bronchoscopy and inhalation of steroid thereafter. To relieve the compression
      which worsened the tracheobronchomalacia, partial resection of the sternal bone
      was performed. This patient died of complications after operation. This case
      suggests the importance of accurate diagnosis and treatment of the mechanical
      ventilation complications including necrotizing tracheitis and
      tracheobronchomalacia which may be life-threating.

PMID- 18634419
TI  - [Successful steroid pulse therapy for acute unilateral oculomotor nerve palsy
      associated with norovirus infection].
AB  - We report a 4-year-old boy who developed acute unilateral oculomotor nerve palsy
      following Norovirus infection. He visited our hospital because of diplopia three
      weeks after Norovirus gastroenteritis. Physical examination showed only the left
      oculomotor nerve palsy. Enhanced MRI of the brain and cerebrospinal fluid
      examination revealed no abnormality. Anti GQlb antibody was negative. Because
      blepharoptosis and ophthalmoplegia progressed rapidly, we performed three courses
      of steroid pulse therapy (methylpredonisolone 30 mg/kg x 3 day/course) combined
      with vitamin B6. Autonomic dysfunction (isocorea, light reflex) began to improve
      in several days and subsequently extraocular movements (blepharoptosis,
      infraduction supraduction, adducent in order) resolved completely in one month.
      Idiopathic oculomotor paralysis is usually believed to be selflimited, but
      steroid pulse therapy should to be considered in cases ocular paralysis is so
      severe or progressive that immune-mediated mechanism was presumed.

PMID- 18634420
TI  - [A 5-year-old boy with nonconvulsive status epilepticus induced by theophylline
      treatment].
AB  - A normally developed 5-year-old boy with no history of convulsive disorder
      presented with a generalized tonic-clonic convulsion on the second day of oral
      theophylline therapy. Although the convulsive seizure was abolished by an
      intravenous bolus of diazepam, he did not regain consciousness. Emergency
      electroencephalography disclosed continuous irregular seizure activity, occurring
      predominantly over the right hemisphere, indicating a diagnosis of nonconvulsive
      status epilepticus (NCSE). The serum theophylline concentration was 19.7
      microg/mL. Treatment with an initial intravenous bolus of midazolam (0.26 mg/kg)
      largely restricted seizure activity to the right hemisphere, with activity then
      diminishing to continuous right occipital spikes. An additional 0.24 mg/kg bolus
      followed by continuous infusion at a rate of 0.20 mg/kg/hr completely abolished
      electrical status. Our case suggests that theophylline treatment can provoke NCSE
      even after successful control of a brief convulsion by initial antiseizure
      treatment in some patients predisposed toward localization-related epilepsy. This
      possibility should be kept in mind in any child receiving theophylline who
      presents with sustained unconsciousness.

PMID- 18634421
TI  - [Multi-center survey of edaravone treatment in children].

PMID- 18634422
TI  - [A newborn with multiple cerebral infarction probably due to the right-to-left
      shunt associated with Ebstein's anomaly and atrial septal defect].

PMID- 18634423
TI  - [Structural basis for biological processes activated by collagen-binding
      proteins].

PMID- 18634424
TI  - [Structural basis for nuclear transport mechanism].

PMID- 18634425
TI  - [Structural biology of a general transcription factor, TFIIE and its interaction
      mode with TFIIH].

PMID- 18634427
TI  - [Molecular mechanism of microtubule plus-end tracking proteins].

PMID- 18634426
TI  - [Structural and biochemical aspects of homologous genetic (DNA) recombination].

PMID- 18634428
TI  - [Structure and mechanism of molybdenum hydroxylase].

PMID- 18634429
TI  - [Crystal structures of heme oxygenase catalytic intermediates unravel the enzyme
      mechanism].

PMID- 18634430
TI  - [Structure and reaction mechanism of azoreductase].

PMID- 18634431
TI  - [Physiological function, reaction mechanism, and structure of cytochrone
      P450nor].

PMID- 18634432
TI  - [Structure and reaction mechanism of D-amino acid oxidase].

PMID- 18634433
TI  - [A questionnaire survey on the theory of postoperative infection prophylaxis in
      urologic surgery].
AB  - The implementation of the Japanese guidelines for prevention of postoperative
      infection in urological surgery, based on the Centers for Disease Control and
      Prevention (CDC) was surveyed. In October 2006, questionnaires about selection of
      prophylactic antibiotics, timing and period of administration, were distributed
      to 25 urologists. Surgical procedures were classified into four categories by
      contamination levels: 1. clean surgery, 2. clean-contaminated surgery, 3.
      contaminated surgery (surgery with urinary tract diversion using the intestine),
      and 4. laparoscopic surgery. Implementation of recommendations was about 70% in
      the selection of prophylactic antibiotics, and 20-30% for the timing of
      administration in four categories. Adequate implementation was low for the timing
      of administration. Period of administration in contaminated surgery was longest
      in all categories. Concerning the administration period and the selection of
      antibiotics for contaminated surgery, marked differences from recommendations
      were seen. Therefore further education in hospitals in Japan is needed.

PMID- 18634435
TI  - [Renal transection conservatively treated three times by selectively
      transarterial embolization (TAE): a case report].
AB  - A 12-year-old-man presented with left flank pain after a traffic accident on
      October 14, 2006. Computed tomography (CT) revealed major left renal hematoma and
      transection (IIIb). Selectively transarterial embolization (TAE) was performed to
      control upper transected renal bleeding on the same day, and again to do
      rebleeding two days later. Because CT revealed left perirenal urinoma caused by
      upper transected kidney on October 18, TAE was performed for the upper transected
      kidney not to function. Five months after left renal injury, CT demonstrated the
      left kidney successfully preserved without hydronephrosis, urinoma and hematoma.
      The patient was well and could be conservatively treated without hypertension and
      other complications. In previous reports, only a part of renal injury (III) cases
      with conservative treatment converted to nephrectomy, whereas approximately half
      of them with surgical treatment resulted in nephrectomy. Therefore, it is
      important to treat them as conservatively as possible and to preserve renal
      function, even in cases of major renal blunt injury.

PMID- 18634434
TI  - [Multi-institute survey on actual conditions of urologic management for severe
      bladder dysfunction after hysterectomy].
AB  - We conducted a multi-institute survey on the conditions related to urologic
      management of severe voiding dysfunction after hysterectomy for uterine cancer
      with or without postoperative irradiation. Our first study population was a group
      of adult female patients currently managed by urologists, using clean
      intermittent catheterization (CIC). Of the 287 patients in this group, 99 (34%)
      had suffered from uterine cancer. Of these patients, 94 underwent hysterectomy
      for this disease; 44 and 30 were treated with or without postoperative radiation,
      respectively, while postoperative irradiation status was unknown for 20. Median
      follow-up after surgery was 21 (0.2-52) years and median interval from operation
      to the introduction of CIC was 4.0 (0-49) years. CIC tended to be introduced
      later for patients with postoperative radiation than those without it. Seventy
      four patients, who required invasive urologic interventions other than CIC for
      voiding dysfunction after hysterectomy, are the second study population. Most of
      these (82%) had received postoperative irradiation. Continuous Foley catheter
      placement was the most frequent procedure. Long-term follow-up and urologic
      management for voiding dysfunction is required for patients undergoing
      hysterectomy.

PMID- 18634436
TI  - [A case of small cell carcinoma of the ureter].
AB  - A 69-year-old man was referred to our hospital with a chief complaint of
      asymptomatic gross hematuria. After radiological evaluations, left
      nephroureterectomy with bladder cuff was performed under a clinical diagnosis of
      a left ureteral tumor (2 cm). Histological examination revealed a small cell
      carcinoma of the ureter (pT3, pN1). After the operation, adjuvant chemotherapy
      with irinotecan, etoposide and cisplatin was administered in combination with
      radiation therapy. At 14 months after the operation, there has been no evidence
      of recurrence. To our knowledge, this is the 22nd report of a small cell
      carcinoma originating from the ureter.

PMID- 18634437
TI  - [Late relapse and urothelial carcinoma of residual ureter 16 years after radical
      nephrectomy: a case report].
AB  - A 66-year-old male was referred to our hospital for evaluation of tumors in his
      left residual ureter and the lung. He had a history of left nephrectomy due to
      "malignant renal tumor", performed by a general surgeon at another hospital 16
      years ago. Since a definitive diagnosis of the kidney was uncertain, we
      speculated that the original renal disease was a renal pelvic cancer and had
      metastasized in the residual ureter and the lung. We performed systemic
      chemotherapy followed by resection of residual ureter with bladder cuff
      Pathological examination revealed urothelial carcinoma. However, the lung tumors
      did not respond to salvage chemotherapy and slowly progressed. Bronchoscopic
      biopsy was performed 2 years later and histological finding showed clear cell
      type renal cell carcinoma.

PMID- 18634438
TI  - [Case report: a case of localized amyloidosis of the ureter].
AB  - A 78-year-old man visited our hospital with a chief complaint ofmacrohematuria in
      January 2006. Ultrasonography and computed tomography showed left
      hydronephroureter due to the enhanced tumor which was 10 mm in diameter in the
      lower ureter. Urine cytology was Class II. Retrograde pyelography could not be
      performed because of severe pain and hematuria. We considered the possibility of
      the malignant neoplasm and performed left total ureteronephrectomy in March 2007.
      The mucosa of the ureter was thickened and sclerosed. Microscopic appearance of
      the surgical specimen shows non-structural fibrosis and stained red with Congo
      red stain. So amyloidosis of the ureter was suspected. After the systemic
      examination, the diagnosis was localized amyloidosis of the ureter. After 8
      months, recurrence has not been pointed out.

PMID- 18634439
TI  - [Estramustine phosphate withdrawal syndrome in relapsed prostate cancer: two case
      reports].
AB  - The decrease of the level of serum prostate specific antigen (PSA) after
      discontinuation of estramustine phosphate (EMP) has rarely been reported. We
      report 2 cases in whom EMP withdrawal syndrome was encountered. Case 1 was a 68
      year-old man with a complaint of paresis of lower limbs. He was diagnosed with
      prostate cancer with multiple bone metastases. The serum PSA level was 9,300
      ng/ml. He was treated with luteinizing hormone-releasing hormone agonist (LH-RHa)
      and bicalutamide (BCL). Six months later, EMP was started against PSA failure.
      During the 3-year treatment with EMP, PSA decreased to the nadir of 0.7 ng/ml and
      gradually increased to 14 ng/ml. After withdrawal of EMP, PSA decreased to 0.3
      ng/ml (97.9% decline) and remained at this level for 4 months. Case 2 was a 61
      year-old man who visited our hospital with gross hematuria. Transurethral bladder
      biopsy and transrectal prostate biopsy were performed. The diagnosis was
      moderately differentiated adenocarcinoma of the prostate that invaded to the
      bladder. Computed tomography (CT) showed a lymph node metastasis. He was treated
      with LH-RHa and BCL. The treatment was changed to EMP after PSA failure. EMP was
      withdrawn when PSA was 30 ng/ml. Then PSA decreased to less than 0.2 ng/ml (99%
      decline) and remained at this level for 9 months. We consider that in patients
      with EMP-resistant progression, EMP withdrawal syndrome should be checked.

PMID- 18634440
TI  - [A case of urinary retention caused by true phimosis].
AB  - We report a case of urinary retention caused by true phimosis in a 67-year-old
      man with untreated diabetes mellitus. The patient could not void in a stream, and
      urine dropped out of the external urethral orifice with manual compression of the
      penis. Subsequently, he visited our hospital due to urinary retention.
      Ultrasonography revealed right hydronephrosis and ballooning of the foreskin. An
      emergency dorsal slit was performed, and hydronephrosis showed immediate
      improvement. Histopathologically, fibrosis and inflammation of the foreskin were
      observed. The mechanisms responsible for urinary retention in this case are
      discussed.

PMID- 18634441
TI  - [A case of paratesticular rhabdomyosarcoma].
AB  - We report a case of paratesticular rhabdomyosarcoma in a 16-year-old male. The
      patient with a mass in the right scrotum was at first diagnosed with testicular
      tumor. Right orchiectomy revealed paratesticular rhabdomyosarcoma. Para-aortic
      lymph node metastasis was pointed out by abdominal computed tomography. Although
      he received multidrug chemotherapy consisting of vincristine, adriamycin,
      cyclophosphamide, cisplatin, and actinomycin-D (IRS-III regimen 35 and IRS-IV
      regimen) without radiotherapy, he died twenty-one months after the operation.

PMID- 18634442
TI  - [Assessment of clinical usefulness of Eviprostat for benign prostatic hyperplasia
      -comparison of Eviprostat tablet with a formulation containing two-times more
      active ingredients].
AB  - We compared the usefulness of Eviprostat tablet, a therapeutic agent for benign
      prostatic hyperplasia (BPH), and EVI-F tablet, a new formulation of Eviprostat
      containing two times more active ingredients (Chimaphila umbellata extract,
      Populus tremula extract, Pulsatilla pratensis extract, Equisetum arvense extract
      and purified wheat germ oil) and consequently designed to reduce the number of
      tablets per dose by half. In this study, patients with BPH were randomly assigned
      to either Eviprostat group (6 tabs/day) or EVI-F group (3 tabs/day) using the
      envelope method. The clinical efficacy of these two drugs were evaluated by the
      International Prostate Symptom Score (IPSS) and QOL score at the end of the
      treatment period, and their safety was evaluated by the incidence of side
      effects. Based on the clinical study guidelines for dysuria, the change in the
      IPSS total score and QOL score were comparable to the previously reported data
      for other treatment agents for BPH, and these indices showed gradual improvement
      with the treatment period. Both treatments were well tolerated. The clinical
      usefulness of the monotherapy with EVI-F tablet or Eviprostat tablet was
      reasonably demonstrated in this study. Furthermore, both treatments reduced
      nocturia, which has an impact on the QOL of patients with BPH.

PMID- 18634444
TI  - [The pathophysiology underlying overactive bladder syndrome possibly due to
      benign prostatic hyperplasia].
AB  - The pathophysiology in the development of overactive bladder syndrome (OAB)
      possibly due to benign prostatic hyperplasia (BPH) has not fully been understood.
      The clinical study in male outpatients aged over 50 years with lower urinary
      tract symptoms showed that the frequency of urgency was significantly associated
      with aging, bladder outlet obstruction (BOO) and benign prostatic enlargement
      (BPE). From the results of the experiments we did using rats, the mechanisms
      underlying the development of OAB were suggested as follows. The functional
      impairment of acetylcholine neuron in the central nervous system is induced by
      aging and decreases the bladder capacity. Non-voiding contractions of the bladder
      may have some bearing on OAB associated with BOO. The C-fiber in the urethra may
      be involved in the generation of the detrusor overactivity associated with BPE.
      These results showed that the pathophysiology of OAB related to BPH is quite
      complex, suggesting that a multidisciplinary approach is necessary for the
      treatment.

PMID- 18634445
TI  - [Examination of the mechanism of ameliorating effect of alpha 1-blocker on
      storage symptoms associated with benign prostatic hyperplasia].
AB  - To investigate the mechanism of the ameliorating effect of alpha1-blocker on
      storage symptoms associated with benign prostatic hyperplasia (BPH), we evaluated
      the effect of tamsulosin on the bladder blood flow in rats with bladder outlet
      obstruction (BOO). BOO was produced by ligature in the part around a proximal
      urethra and kept for 2 weeks. Tamsulosin was subcutaneously administered with an
      osmotic pump for 2 weeks immediately after the BOO operation. Bladder blood flow
      in the sham-operated rats, the control BOO rats and the tamsulosin-treated BOO
      rats was measured by the fluoro-microsphere method. Bladder blood flow was
      significantly reduced in BOO rats compared with sham-operated rats, and
      tamsulosin significantly increased the bladder blood flow in BOO rats. The
      present results suggest that the increase in bladder blood flow by tamsulosin
      contributes to the improvement of storage symptoms associated with BPH.

PMID- 18634446
TI  - [The role of alpha1-adrenoceptor subtypes in benign prostatic hyperplasia-from
      bed to bench].
AB  - Alpha 1-adrenoceptors (alpha1-ARs) play a role in the regulation of prostatic
      smooth muscle tone, and are critical mediators of lower urinary tract symptoms
      (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH). Three subtypes
      (alpha1a, alpha1b, alpha1d) have been identified by molecular cloning techniques.
      Although the reasons for the existence of three subtypes remain elusive, recent
      findings suggest a role of subtype and tissue-specific regulation. We examined
      the role of each alpha1-AR-subtype in the prostate to apply some new findings
      obtained from basic research for the clinical treatment. We have demonstrated
      that the mRNA expression levels of alpha1-AR-subtypes in the prostate differed
      among patients and that the genetic background differences of patients with BPH
      were responsible for the diverse responses to subtype-selective alpha1-blockers.
      In addition, both alpha1a- and alpha1d-AR-subtypes play a significant role in the
      spontaneous contraction of human prostate and, especially alpha1d-AR-subtypes may
      also control the cell growth of the prostate. Clarification of the mechanism of
      alpha1-AR subtypes in the prostate will provide more effective therapy for BPH
      patients.

PMID- 18634447
TI  - [Effect of Goshajinkigan on storage symptoms in prostatic disease--fundamental
      researches of Chinese herbal medicine for voiding dysfunction and its future
      aspects].
AB  - At present, patients with lower urinary tract symptoms, including storage
      symptoms, caused by prostatic disease are predominantly treated with alpha1
      adrenoceptor antagonist and anticholinergic agents. However, some patients are
      not improved by this treatment. We investigated the efficacy of Goshajinkigan in
      25 patients with prostatic disease in whom pollakisuria was not improved by
      treatment with drugs for lower urinary tract symptoms. The urinary frequency was
      significantly improved both in the daytime and at night. The parameters of
      uroflowmetry, the residual urine volume, the international prostate symptom score
      and QOL score were also improved after therapy. It was considered that the
      pollakisuria was improved by Goshajinkigan induced activation of spinal kappa
      opioid receptors, which inhibited the micturition reflex via blunting of bladder
      sensation. The inhibition of C-fiber and the down regulation of Fos protein in
      the pontine micturition center were also suggested to be related with improvement
      ofpollakisuria. Chinese herbal medicine therapy is different in various aspects
      from Western medicine. Clarification of the mechanisms of Chinese herbal medicine
      and Sho (patient status in Chinese herbal medicine) is awaited.

PMID- 18634448
TI  - [Results of repeated QFT-2G checkings at two-year interval and their comparison
      with TST results introduced into infection control program for staffs working at
      a hospital with isolation wards for tuberculosis].
AB  - OBJECTIVE: In Fukujuji Hospital, we have been conducting TST to tuberculosis (TB)
      non-infected staffs to find new latent TB Infection (LTBI) every year, although
      almost of them were BCG vaccinated, and the reliability of TST is controversial
      in BCG vaccinated group. Recently, a new technique, QFT-2G, is evaluated highly
      to detect TB infection, especially in BCG vaccinated individuals. We examined
      hospital staffs twice at two-year interval using QFT-2G and TST, and compared
      these data. MATERIAL & METHOD: About four hundreds fifty staffs in Fukujuji
      Hospital with isolation wards for tuberculosis, provided with high level program
      against nosocomial infection of TB were examined. Almost all of them were BCG
      vaccinated. Because one fifth to one seventh of them were supposed as TB non
      infected, they had been examined with TST to find new LTBI every year. QFT-2G was
      applied for about 80-85% of staffs twice, 2003 Jan. and 2005 Jan., with each
      person's consent. We compared the sequential changes of TST reactions and QFT-2G
      data. RESULTS: (1) The positive rate of QFT-2G was approximately 10% in both two
      year interval checkings. (2) Two hundreds twelve persons, about half of staffs,
      were sequentially checked QFT-2G twice at two-year interval. 19 persons were
      positive at both checkings, 4 converted to negative and 7 converted to positive,
      suggesting that the rate of new LTBI in staffs would be 3.7% [7/(212-19-4)]
      during 2 years, 1.85% per year by QFT-2G conversion. (3) In comparison with data
      between TST and QFT-2G, QFT-2G was positive only in 13% of staffs with strongly
      reactors to TST. Moreover, even in 13 staffs converted by TST reaction to strong
      positive and highly suspected of new LTBI at two-year interval, there were no
      positive and positive converted persons based on QFT-2G checkings. Lastly, out of
      7 staffs who converted to positive by QFT-2G checkings, only one was tested with
      TST, and no increase in the intensity of TST was observed. CONCLUSION: The QFT-2G
      positive rate was about 10% and the new TB infection rate was estimated to be
      1.85% par year in staffs of a hospital with TB wards provided with high level
      programs against nosocomial TB infection. In addition, there are apparent
      disagreements between the results of QFT-2G and TST reactions, presumably
      affected by prior BCG vaccination. Therefore we must be cautious to detect new
      LTBI by ordinary TST in BCG vaccinated group.

PMID- 18634449
TI  - Pharmaceutical study of suppository formulations for improved in vivo kinetics of
      rifampicin.
AB  - PURPOSE: To study rifampicin (RFP) suppository formulations that were prepared by
      adding an absorption promoter and a holding agent to conventional rifampicin
      suppositories in order to achieve higher blood drug levels. SUBJECTS AND METHODS:
      The subjects were 3 healthy volunteers who gave consent to participate in this
      study. Suppository formulations were prepared by adding sodium caprinate (the
      absorption promoter) to 600 mg, 750 mg, or 900 mg of RFP at about 3% of the
      suppository weight and sodium alginate (the holding agent) at 25% of the RFP
      content. Serum samples collected at 2, 6, and 10 hours after insertion of a
      suppository were subjected to RFP concentration analysis. RESULTS: In subject no.
      1, the maximum concentration was 0.807 Lg/ml, 1.093 microg/ml, and 1.291
      microg/ml after administration of a suppository containing 600 mg, 750 mg, or 900
      mg of RFP, respectively. DISCUSSION: Since an injectable RFP formulation has not
      been approved in Japan, formulation studies of RFP suppositories are important to
      achieve a better clinical response and to prevent the development of resistance.
      The present formulation that delivered a blood concentration of RFP considerably
      higher than 1 microg/ml was considered to have therapeutic potential. Its
      clinical utility will be examined in further formulation studies.

PMID- 18634450
TI  - [Risk factors for side effects due to the use of antituberculous drugs in elderly
      patients].
AB  - PURPOSE: This study was designed to evaluate incidence of clinical risk factors
      for side effects due to the use of antituberculous drugs. METHOD: We
      retrospectively analyzed clinical records of 229 elderly patients with
      tuberculosis treated at our hospital. RESULTS: Temporary stop of antituberculous
      therapy proved to be needed because of side effects in 77 patients (33.6%).
      Adverse effects leading to drug discontinuation were liver dysfunction (15.7%),
      gastrointestinal dysfunction (7.0%), and skin rash (5.7%); other effects
      accounted for discontinuation in 5.2%. Risk factors for liver dysfunction
      according to Cox proportional hazards regression analysis were complications of
      HCV infection (hazard ratio or HR, 2.97; 95% confidence interval or CI, 1.20 to
      7.38; p=0.019); hepaocellular injury present at admission (HR, 3.37; 95% CI, 1.56
      to 7.29; p=0.002); and dose of isoniazid (per mg/kg, HR, 1.40; 95% CI, 1.05 to
      1.85; p=0.02). Body mass index was a risk factor for gastrointestinal dysfunction
      (per kg/m2, HR, 0.83; 95% CI, 0.70 to 0.98; p=0.026). CONCLUSION: Such
      identification of risk factors for side effects from antituberculous therapy in
      elderly tuberculosis patients would minimize adverse effects.

PMID- 18634451
TI  - [Characteristics of 109 index cases in TB outbreak].
AB  - OBJECTIVES: To elucidate characteristics of index cases in TB outbreak. SUBJECTS
      AND METHODS: The subjects of this retrospective study were 109 index cases in TB
      outbreak observed in Japan between 2003 and 2005, and reported to the Ministry of
      Health, Labour and Welfare. An index case rate (ICR) for a category of patients
      was defined as following; ICR=NI/NA, where NA: Number of TB patients in a
      category A, and NI: Number of index cases in category A. RESULTS: Of the 109
      patients, 20 were female and 89 were male. Smear-positive pulmonary TB patients
      were 102 in number, and separated to 87 patients with cavitary lesion on a chest
      X-ray and 15 without cavitary lesion, and the remaining 7 patients were smear
      negative and culture-positive pulmonary TB patients. The index case rates were
      0.46% for smear-positive cavitary patients, 0.10% for smear-positive non-cavitary
      patients, and 0.04% for smear-negative culture-positive patients. The differences
      were highly significant between smear-positive cavitary patients and smear
      positive non-cavitary patients, as well as between smear-positive cavitary
      patients and smear-negative culture-positive patients (p<0.001). In 57 male
      patients with smear-positive cavitary lesion, the index case rates were
      significantly different between the thirties and the forties (1.84% vs 0.61%,
      p<0.01). All patients were grouped by age to a younger group with 10 to 39 years
      of age, a middle aged group with 40 to 69 years, and an elder group with 70 years
      or higher. The index case rates in smear-positive cavitary patients were 2.32%
      for the male younger group, 0.37% for the male middle group, 0.06% for male elder
      group, 0.41% for the female younger group, 0.37% for the female middle group, and
      0% for female elder group. The differences were highly significant between the
      male younger group and the male middle group, as well as between the male younger
      group and the female younger group (p<0.001). The index case rates for smear
      positive cavitary patients were significantly higher than non-cavitary patients
      in two categories; 1.58% versus 0.21% for the younger group (p<0.001), and 0.37%
      versus 0.11% for the middle aged group (p<0.05). CONCLUSION: These findings
      suggest that TB outbreak risk is the highest in those patients categorized to be
      smear-positive, cavitary, younger group, and male.

PMID- 18634452
TI  - [Comparison of BBL Mycoprep and 2%NaOH decontamination procedures for MGIT].
AB  - OBJECTIVES: We compared the BBL Mycoprep (Becton Dickinson Japan) and home-made
      2%NaOH decontamination procedures by using an equal amount of expectorated sputum
      in the aerosol-free 30 ml KT centrifuge tube with the rugged inner surface.
      METHOD: A total of 113 sputum specimens obtained in NHO Kinki-Chuo Chest Medical
      Center in November 2004 were subjected to two decontamination methods. All
      specimens were divided into two equal portions after concentrating the sediments
      processed by semi-kaline protease (SAP), then decontaminated, and inoculated into
      MGIT. The tubes were incubated at 37 degrees C and monitored for up to forty
      second days. RESULTS: Comparing these decontamination procedures, the time of the
      recovery of mycobacteria strains in the 2%NaOH (mean 8 days) was significantly
      faster than in the BBL Mycoprep (mean 11 days). Of these, 19 specimens (16.9%)
      processed by the BBL Mycoprep were positive for growth of mycobacteria, and
      similarly 18 specimens (16.0%) processed by the 2%NaOH (p>0.5) were positive. The
      19 mycobacteria recovered by the BBL Mycoprep were identified as 14 M.
      tuberculosis strains and 5 NTM strains. The decontamination rate was 0.9% in
      2%NaOH and 6.2% in Mycoprep, however the difference was statistically not
      significant (p>0.5). DISCUSSION: We verified that the 2%NaOH was an alternative
      method suitable for the digestion and decontamination procedure, and 2%NaOH was
      useful for the isolation and detection of mycobacteria as well.

PMID- 18634453
TI  - [Human resource capacity building on TB laboratory work for TB control program-
      through the experience of international TB laboratory training course for TB
      control at the Research Institute of Tuberculosis, JATA, Japan].
AB  - The international training course on TB laboratory work for national tuberculosis
      program (NTP) has been conducted at the Research Institute of Tuberculosis since
      1975 funded by Japan International Cooperation Agency in collaboration with WHO
      Western Pacific Regional Office. The aim of the course is to train key personnel
      in TB laboratory field for NTP in resource-limited countries. The course has
      trained 265 national key personnel in TB laboratory service from 57 resource
      limited countries in the last 33 years. The number of participants trained may
      sound too small in the fight against the large TB problem in resource-limited
      countries. However, every participant is playing an important role as a core and
      catalyst for the TB control program in his/her own country when they were back
      home. The curriculum is composed of technical aspects on TB examination, mainly
      sputum microscopy in addition since microscopy service is provided at many
      centers that are deployed in a widely spread area, the managerial aspect of
      maintaining quality TB laboratory work at the field laboratory is another
      component of the curriculum. Effective teaching methods using materials such as
      artificial sputum, which is useful for panel slide preparation, and technical
      manuals with illustrations and pictures of training procedure have been developed
      through the experience of the course. These manuals are highly appreciated and
      widely used by the front line TB workers. The course has also contributed to the
      expansion of EQA (External Quality Assessment) system on AFB microscopy for the
      improvement of the quality of TB laboratory service of NTP. The course is well
      known for not only having a long history, but also for its unique learning method
      emphasizing "Participatory Training", particularly for practicum sessions to
      master the skills on AFB microscopy. The method in learning AFB microscopy, which
      was developed by the course, was published as a training manual by IUATLD, RIT
      and USAID. As it is mentioned, the course has been contributing to human resource
      capacity building including management of laboratory service to improve NTP in
      the resource-limited countries. Currently, expansion of technology transfer on
      culture examination for drug susceptibility test has been attempted to the
      resource-limited countries due to the occurrence of MDR-TB (Multi drug-resistant
      tuberculosis) and XDR-TB (Extensively drug-resistant tuberculosis) cases.
      However, since sputum smear examination is most effective method of detection of
      infectious TB, the writers believe it is still a core component of TB control,
      unless a new diagnostic tool that is practicable and effective in the resource
      limited countries is developed. Therefore the course will keep focused on the
      smear examination as the basic curriculum. The course is highly appreciated by
      international experts and it is our responsibility to answer the expectation from
      them.

PMID- 18634454
TI  - [Significant factors affecting the operation time for benign parotid tumor].
AB  - Tumors of the parotid gland are fairly frequent among head and neck tumors.
      Parotidectomy for benign tumors is necessary for diagnosis and therapy.
      Furthermore, acquiring the skill for this operation is a significant step in the
      training course of an otolaryngologist Thus, it is useful to analyze the
      operation time and determine the factors affecting it to evaluate the progress in
      the operation skill. To measure the operation time and determine the factors
      affecting it, 71 cases, including 43 cases of pleomorphic adenomas and 28 cases
      Warthin's tumor, were retrospectively reviewed to the determine if the operation
      time depended on the age, sex, operated side, presence of complications, BMI,
      bleeding volume, tumor size, tumor location, exposure of branches of the facial
      nerve, and experience of the surgeon. Multivariate analysis was used to determine
      the factors correlated with the operation time. The results revealed that the
      bleeding volume, tumor size, tumor location and experience of the surgeon were
      significantly correlated with the operation time, whereas age, sex, operated
      side, presentation of complications and BMI showed no correlation with the
      operation time. Furthermore, surgeons with the experience of operating 20-39
      cases took almost the same time for the operation as the surgeon with the
      experience of operating more than 40 cases. Taken together, to shorten the
      operation time, the inexperienced surgeon should start with smaller tumors and
      surgery in the superficial lobe in the initial training period, and supervision
      by well-experienced supervised surgeons is required until 30-40 are undertaken.

PMID- 18634455
TI  - [Clinical study of cervical lymph node metastasis in maxillary cancer patients].
AB  - The clinical characteristics of lymph node metastasis in maxillary cancer
      patients were analyzed. Thirty-eight (23%) of the 166 patients who received
      intial treatment at Kurume University Hospital between 1978 and 2003 had cervical
      lymph node metastasis at the time of diagnosis. The disease-specific 5-year
      survival rate was 63% in the lymph node metastasis negative group and 18% in the
      lymph node metastasis positive group (p<0.01). There was a statistically
      significant correlation between bone invasion and lymph node metastasis in the
      case of the group with bone invasion of the posterior wall of the maxillary
      sinus. Cervical neck lymph node metastasis developed in 38 (28%) of 135 posterior
      wall-invasion-positive group and in none (0%) of the 31 patients in the negative
      group (p<0.01). Because distant metastasis is common in patients with lymph node
      metastasis, postoperative adjuvant chemotherapy is highly recommended.

PMID- 18634456
TI  - [Structual changes of the apex region of the tongue in the elderly].
AB  - The purpose of this research was to clarify the morphological changes of the apex
      region of the tongue in the elderly. Apexes of tongue were removed from 44
      Japanese adult cadavers (64-99 years) which were contributed for dental studies
      at Tokyo Medical and Dental University. These specimens were fixed again with 10%
      formaldehyde, and then paraffin sections were made from these specimens according
      to a general method. After several stainings, these sections were observed with a
      light microscope. The results were as follows : 1) The epithelium, propria
      mucosae and muscle layers became thin with aging, and the boundaries between
      these layers became unclear. 2) The tendencies of fibrosis also became
      remarkable, and the arrangement and distribution of collagen fibers and elastic
      fibers became disordered in propria mucosae. 3) The numbers of myocytes and
      myofibrils tended to decrease. 4) The connective tissue which is the outer layer
      of nerves tended to increase. Moreover, in some nerves, the paths of each
      neurofibril became tangled. 5) These findings are structural features in the apex
      of the tongue of the elderly, involving morphological changes of layers,
      fibrosis, structural changes of myocytes and myofibrils, nerves and neurofibrils
      in this region. These changes suggest some relationships to functional disorder
      in motion, pain and paresthesia of the tongue.

PMID- 18634457
TI  - [Observations on the dentino-enamel junction--net-like structures on decalcified
      dentin surface].
AB  - As part of morphological research to investigate the development and function of
      the human dentino-enamel junction, structural features of net-like structures on
      the decalcified dentin surface of upper and lower incisors were observed by using
      stereoscopic microscope, and scanning and transmission electron microscopes. The
      results were as follows : 1) The net-like structures on the decalcified dentin
      surface were stained by hematoxylin, orange G phosphomolybdic acid, toluidine
      blue and aniline blue. 2) The majority of net-like structures were covered with a
      membrane-like structure. 3) An individual reticulation of net-like structures
      corresponds to the margin of each dentin foveolus. 4) The dentin crystals
      situated in the vicinity of the dentinoenamel junction were larger than the
      crystals of usual dentin and were more closely aligned. On the other hand, the
      enamel crystals in this region were smaller than those in other layers of enamel.
      The surface dentin in the vicinity of the dentino-enamel junction seemed to be
      highly calcified. 5) It was possible to clearly demonstrate the outline and
      distribution of dentin foveolus by using certain dyes on the decalcified
      specimen. 6) By observing the distribution and structural features of net-like
      structures in detail by applying this dye method to human and animal teeth, the
      formation mechanism of the dentino-enamel junction and functions of those teeth
      were elucidated morphologically.

PMID- 18634458
TI  - [Structural features of ectopic bone-like tissue in porous hydroxyapatite
      blocks].
AB  - Calcium phosphate ceramics are widely used as bone substitutes because of their
      favorable biocompatibility and osteoconductivity. Some studies have reported that
      porous hydroxyapatite (HA), with its special structure, implanted at ectopic (non
      bone) sites, exhibits osteoinductive activity. However, few studies have examined
      the detailed ultrastructure of mineralized tissue formed in biomaterials like HA.
      Therefore, it is important to examine whether the mineralized tissue exhibits
      structural characteristics of normal bone tissue. Thus, in this study, we
      subcutaneously implanted hydroxyapatite blocks (5 x 5 x 7 mm) into the backs of
      adult dogs, and performed detailed morphological examination of the bone-like
      tissue formed, which showed a lamellar structure. Immunohistochemical staining
      revealed that the matrix fibers of the bone-like tissue were mainly composed of
      type I collagen. The pattern of crystal deposition in matrix fibers and the
      structure of osteoblast-, osteocyte-, bone-lining-, and osteoclast-like cells
      were similar to those of normal bone tissue and osteogenic cells, respectively.
      These results indicate that cellular events observed in normal bone formation and
      remodeling occur in bone-like tissue as well, and suggest that bone-like tissue
      in HA blocks is very similar to bone tissue.

PMID- 18634459
TI  - Stem-cell therapy for pets. Sorry, people. A new treatment for ailing joints is
      only for pooches (and cats and horses).

PMID- 18634460
TI  - Towards the elimination of rabies in Eurasia. Foreword.

PMID- 18634461
TI  - The control of rabies in Eurasia: overview, history and background.
AB  - After a short overview of the present and past epidemiological situation
      regarding animal and human rabies in Eurasia, the general characteristics of the
      disease are described in each vector. Three main rabies cycles are presently
      established in Eurasia: in dogs, wild carnivores and insectivorous bats. Because
      of the strong barrier that exists between species-adapted rabies viruses and
      various potential hosts, these cycles are quite independent. They are perceived
      in many countries in Eurasia not to have a significant impact on animal health or
      the rural economy in general; the loss of dogs (or cattle) is not a priority
      animal health issue at the national level. Wildlife rabies has almost been
      eliminated in Western Eurasia by oral vaccination campaigns. Bats do not
      represent a real threat for a well informed public. Rabies is thus essentially a
      public health issue. Human rabies of canine origin has continued unabated for
      centuries in Eastern Eurasia, despite the Pasteur treatment and subsequent
      improvements of rabies post-exposure prophylaxis and biological products. Dog
      rabies, which is the main source of human contamination, remains practically
      uncontrolled. The Ministries of Health of all infected countries of Eurasia
      should focus their attention on canine rabies first, as it incurs endless
      expenses for treating humans that have been exposed to dog bites. These
      Ministries should use the competence of Veterinary Services and all other
      national bodies involved in dog rabies control, and contribute all necessary
      resources to support them to control this reservoir. This goal seems achievable
      in less than five years in a country, provided that cost-shared and well-planed
      mass canine oral vaccination campaigns are organised and coordinated at the
      regional and international levels. The conditions for the success of such
      campaigns are presented.

PMID- 18634462
TI  - The rabies situation in Western Europe.
AB  - This analysis of the present rabies situation in Western Europe is based on
      completed questionnaires from 16 countries. The questionnaire focuses on the
      years 2005 and 2006. Additional information was obtained from the Rabies Bulletin
      Europe, and from the OIE's publication on "Historical Perspective of Rabies in
      Europe and the Mediterranean Basin". Rabies in domestic animals and wild
      carnivores has become very rare in Western Europe. Only Germany reported a low
      number of rabid foxes for 2005. Bat rabies was observed in four countries. One
      imported human case was seen in the UK, while Germany reported four cases in
      transplant recipients. Wildlife vaccination campaigns were conducted by Austria,
      Germany and France. Reporting of human post-exposure prophylaxis is inconsistent
      due the lack of information. Similarly, data on domestic animal rabies
      prophylaxis seem to be difficult to collect.

PMID- 18634463
TI  - The rabies situation in Eastern Europe.
AB  - An overview of the rabies situation in the 19 countries of Central and Eastern
      Europe covering more than 2.5 million km2 is presented. In 2005, 6,500 cases of
      rabies were registered in this region with 31% in domestic animals and 69% in
      wild animals. Rabies was found in a limited number of dogs in 10 countries, and
      sporadically in three countries with seven cases in bats. A similar situation
      existed in 2006. Rabies is very rare in humans: 2 cases were reported in Belarus
      in 2006. Around 40,000 people are treated yearly due to rabies exposure. The main
      vector and reservoir is the red fox (Vulpes vulpes), with a 50% incidence in
      positive findings. The raccoon dog (Nyctereutes procyonoides) is another
      significant vector, mainly in the Baltics. Oral vaccination is used in varying
      degrees in 10 countries, with promising results. Two countries are currently
      rabies free, and several others are close to being rabies-free. An unfavourable
      situation remains mainly in the Baltics and nearby eastern countries, and also in
      some Balkan regions. All countries studied have national reference laboratories,
      appropriate legislation, and rabies as a notifiable disease.

PMID- 18634464
TI  - The rabies situation in Central Asia.
AB  - Rabies is a serious problem in the 11 states that make up CentralAsia. More
      information is needed to make rabies control effective in Central Asia. It is
      necessary to assess the national programmes, identify the main rabies carriers,
      increase the number of vaccinated dogs and cats with the aim of preventing rabies
      cases, and to use the worldwide experience of rabies eradication by the oral
      vaccination of wildlife.

PMID- 18634465
TI  - The rabies situation in the Middle East.
AB  - Rabies is a public health problem of significant importance in the majority of
      Southern and Eastern Mediterranean and Middle Eastern countries. In some of these
      countries, there is a considerable death rate due to rabies. Dogs are the main
      source of human infection, while cats constitute the second most important group
      of domestic animals followed by cattle, sheep, goats, camels, donkeys and then
      wild animals. There are around 300 reported human cases in these regions
      annually, with several hundred thousand post-exposure treatments. Laboratory
      confirmation of rabies cases is not always performed. In most countries, there is
      one central rabies diagnosis laboratory with trained staff and the diagnosis
      capability of district laboratories is weak. Animal rabies control consists of
      the vaccination of dogs and cats, the elimination of stray animals, health
      education for the public, etc. Mass vaccination of dogs is not implemented, and
      the effective coverage rate is not exactly known. The elimination of stray dogs
      and other animals by shooting and poisoning is still implemented in certain
      countries, however, this has a minimal effect on rabies transmission. Certain
      countries of the Middle East region are facing increasing problems due to
      wildlife rabies, including Saudi Arabia, Oman, Yemen, Israel, Iran and Turkey.
      The red fox (Vulpes vulpes) and golden jackal (Canis aureus) are usually
      involved. Coordinated actions to confront the serious rabies public health and
      economic problems should be undertaken by affected countries, with the assistance
      of international organisations, under conditions that are suitable for each
      country.

PMID- 18634466
TI  - The rabies situation in Far East Asia.
AB  - This study evaluated rabies epidemiology in Far EastAsia. Questionnaires were
      sent by the OIE to Far East Asian countries and eight questionnaires were
      returned. Data were collected from these returns, as well as from recent
      publications, to gather information regarding rabies epidemiology in these
      countries. More than 29,000 human deaths were reported in 2006 in Far East Asia,
      representing more than 50% of all human rabies cases around the globe. There are
      only a few countries or regions from which no human rabies was reported in 2006
      such as Japan, Singapore, South Korea, Malaysia, Hong Kong, and Taiwan. In many
      of these rabies endemic countries, the number of human rabies cases has not
      changed much during the past decade. The only country with a steady decline is
      Thailand, where the number of cases has decreased from around 200 to about 20
      cases per year. The most dramatic changes were observed in China. Human rabies
      cases declined from around 5,000 cases per year in the 1980s to about 160 in the
      mid-1990s. However, these trends have since been reversed. A steady increase has
      been reported over the past 10 years with more than 3,200 cases reported in 2006.
      Although there are many factors that contribute to the epidemic or endemic nature
      of rabies in these countries, the single most important factor is the failure to
      immunize domestic dogs, which transmit rabies to humans. Dog vaccination is at or
      below 5% in many of these countries, and cannot stop the transmission of rabies
      from dogs to dogs, thus to humans. It is thus most importantforthese countries to
      initiate mass vaccination campaigns in dog populations in order to stop the
      occurrence of human rabies in Far East Asia.

PMID- 18634467
TI  - Inflammatory responses in the nervous system of mice infected with a street
      isolate of rabies virus.
AB  - Rabies virus causes severe encephalitis that is invariably fatal for the victim.
      However, the contribution of the virus and the host to damage of the CNS is
      unclear. In order to investigate this we studied the neuropathology and CNS gene
      expression patterns in a murine model of rabies using a 'street' isolate RV61.
      This virus was derived from a human case of disease. In this model, infection of
      the CNS progresses rapidly following inoculation in the periphery, leading to
      extensive virus replication in the brain and the development of disease. However,
      previous studies have found little evidence of inflammation and lymphocyte
      infiltration in many regions of the CNS of infected mice. During the current
      study virus replication was detected in the dorsal root ganglia (DRG), spinal
      cord, brain and salivary gland at 11 days postinfection (dpi). Mononuclear cell
      infiltration was observed in the DRG and to a lesser extent, the spinal cord.
      Immunolabelling demonstrated that T-lymphocytes were the dominant population of
      infiltrating cells. Murine innate immune response gene transcripts were detected
      in the brain as early as 5 dpi. At 11 dpi, coincidentwith the onset of disease,
      elevated levels of mRNA transcripts were recorded for type-1 (alpha and beta) and
      type-2 interferon (gamma) and certain chemokines (CCL5 and CXCL10) with
      chemotactic properties for T-cells. We suggest that damage to the DRG and spinal
      cord could be due to a combination of both virus infection and the infiltration
      of T-cells.

PMID- 18634468
TI  - Role of virus-induced neuropeptides in the brain in the pathogenesis of rabies.
AB  - Rabies virus (RABV) infection is characterized by the rapid neuronal spread of
      RABV into the CNS before a protective immune response is raised. Therefore, a
      typical feature of RABV infection is the paucity of inflammatory reactions in the
      brain. Here we examined whether the induction of immunosuppressive neuropeptides,
      in particular CGRP, may contribute to the ability of RABV to evade immune
      responses. RABV infection of mice caused a strong induction of calcitonin gene
      related peptide (CGRP) in neurons and fibres in the neocortex as well as in the
      dentate gyrus and CA1 region of the hippocampus although RABV did not infect
      neurons in which CGRP expression was upregulated. Neuropeptide Y (NPY) or
      vasoactive intestinal peptide (VIP) expressing neurons also were not infected by
      RABV. In contrast, somatostatin neurons were infected by RABV. There was evidence
      for an RABV-induced increase of VIP and somatostatin but not of NPY. To test how
      CGRP expression is related to TNFalpha-induced enhancement of CNS innate and
      adaptive immunity during RABV infection, we used recombinant RABVs that contained
      either an active (SPBN-TNFalpha(+)) or an inactive (SPBN-TNFalpha(-)) TNFalpha
      gene. As compared to SPBN-TNFalpha(-), infection with SPBN-TNFalpha(+) attenuated
      the induction of CGRP but simultaneously enhanced induction of the invariant
      chain of MHC II, microglial activation and T cell infiltration. In conclusion,
      distinct neuropeptidergic neurons in the brain are remarkably spared from RABV
      infection suggesting a pivotal role of neuropeptides during CNS virus infection.
      Given the inhibitory effect of CGRP on antigen presentation, we propose that the
      strong RABV-induced upregulation of CGRP in the brain may contribute to the
      mechanism by which RABV escapes immune detection. Targeting the expression of
      neuropeptides, in particular CGRP, that are induced during RABV infection may
      open a new avenue for therapeutic intervention in human rabies.

PMID- 18634469
TI  - Pathogenic rabies virus alters host protein expression in the central nervous
      system: implications for neuronal dysfunction.
AB  - Proteomics technology was employed to profile host responses to rabies virus
      (RABV) infection in order to understand how RABV infection results in neuronal
      dysfunction. In mice infected with wild-type (wt) RABV, the expression of
      proteins involved in ion homeostasis was altered. H+ ATPase and Na+/K+ ATPase
      were up-regulated while Ca2+ ATPase was downregulated, which resulted in
      reduction of intracellular Na+ and Ca2+ concentrations. Furthermore, infection
      with wt RABV resulted in down-regulation of SNAREs such as alpha-SNAP, TRIM9,
      syntaxin, and pallidin, all of which are involved in docking and fusion of
      synaptic vesicles to and with the presynaptic membrane. As a consequence, the
      accumulation of synaptic vesicles was observed in the presynapses of mice
      infected with wt RABV. These data demonstrate that infection with wt RABV results
      in the alteration of host protein expression, particularly those involved in ion
      homeostasis and docking and the fusion of synaptic vesicles to the presynaptic
      membrane, which may lead to neuronal dysfunction.

PMID- 18634470
TI  - Can rabies be eradicated?
AB  - Rabies, an acute progressive encephalitis, is an ancient zoonosis. Its
      distribution encompasses all continents, except Antarctica. Agents consist of at
      least 11 species orgenotypes of rhabdoviruses, in the Genus Lyssavirus.
      Susceptible natural hosts include all mammals. Primary reservoirs reside in the
      Orders Carnivora and Chiroptera. A plethora of variants, maintained by a
      diversity of abundant hosts, presents a challenge to a strict concept of true
      eradication. Globally, the domestic dog remains the most significant species for
      viral transmission, responsible for millions of suspect human exposures and tens
      of thousands of fatalities. As such, this single major target provides an ideal
      opportunity for focused intervention programmes in humane disease prevention and
      control, driven by laboratory-based surveillance and guided via modern
      epidemiological insights. Historically, substantial technical progress throughout
      the 20th century led to the development of safe, affordable and efficacious
      animal and human vaccines, resulting in declining disease burdens in selected
      developed and developing countries. Regional and local disease resurgence occurs,
      due in part to a combination of political and economic instability, environmental
      perturbations, and shifting government priorities. Society must recall that
      despite the recent recognition of other important emerging infectious diseases,
      none exceed the case fatality rate of rabies. Given the clear relevance of rabies
      in public health, agriculture, and conservation biology, substantive
      international progress must continue towards enhanced public awareness, human
      rabies prevention, wildlife rabies control, and canine rabies elimination, with
      renewed collaborative vigour.

PMID- 18634471
TI  - Molecular epidemiology of lyssaviruses in Eurasia.
AB  - The Lyssavirus genus, a member of the Rhabdoviridae family, consists of seven
      established related viruses (genotypes 1-7). Rabies cases in Eurasia are
      principally attributed to three of these genotypes, namely genotype 1 (RABV,
      classical rabies) and to a lesser extent genotypes 5 and 6 (European bat
      lyssaviruses type-1 and -2). In addition, four newly identified divergent
      lyssaviruses have been isolated from insectivorous bats. The molecular diversity
      of classical rabies viruses (genotype 1, RABV) has been studied at the global
      level and reference has been made to the existence of a number of European
      strains in a range of mammalian species. It is accepted that these viruses
      cluster within a 'Cosmopolitan Lineage' having ancestral roots in Europe in the
      17th century before its widespread dispersal to Asia, Africa and the Americas as
      a result of European exploration and colonization.

PMID- 18634472
TI  - Rabies in South Asia: epidemiological investigations and clinical perspective.
AB  - A five year study (1995-1999) was conducted in Northern India to investigate
      epidemiological aspects of rabies in domestic animals. For this purpose, brain
      tissue samples were collected from rabies suspect animals including 231 dogs, 79
      buffaloes, 46 cattle and 28 wild species. Out of the 384 rabies suspected cases,
      56% were positive for rabies by fluorescent antibody test (FAT), the mouse
      inoculation test (MIT) and histopathological techniques. Variations in clinical
      signs of rabies were recorded for individual animals with significant differences
      observed between dogs and bovines with respect to hypersalivation, paralysis,
      recognition of owners and aggression. Likewise, differences in the clinical
      course of disease between cows and buffaloes regarding hypersalivation and
      micturition were observed. Rabies incidence was highest among adult male dogs and
      indicated a seasonal pattern with more rabies cases during certain months of the
      year (January to April, and August to November). Its impact on cow/buffalo rabies
      is discussed. Accumulated history records revealed that 78% of owned rabid dogs
      were not prophylactically vaccinated against rabies.

PMID- 18634473
TI  - Stray dogs in Bangkok, Thailand: rabies virus infection and rabies antibody
      prevalence.
AB  - In Thailand, the animal most reported rabid is the stray dog. Dog bite related
      rabies cases in humans account for 70-95% of rabies related deaths. The reported
      incidence of dog bites is highest in the central part of the country, especially
      in Bangkok. This epidemiological survey shows that at least five different canine
      rabies virus types are present in Bangkok. Rabies antigen and antibody prevalence
      in stray dogs in Bangkok was also investigated. Saliva and serum samples were
      taken from 3,314 stray dogs, captured between December 2003 and June 2004. One
      two year-old female was antigen positive by latex agglutination test and the
      result was confirmed by reverse transcription-polymerase chain reaction (RT-PCR).
      The overall antibody seroprevalence by enzyme-linked immunosorbent assay was 62%
      (95% CI: 54, 70%). Antibody seroprevalence was higherfor dogs captured within
      central Bangkok (86% of 1,208 dogs captured) than in the dogs captured on the
      outskirts of the greater metropolitan area (49% of 2,106 dogs captured). If our
      sample of stray dogs is representative, then the seroprevalence achieved from
      previous vaccination campaigns is insufficient in order to break the rabies
      transmission cycle among stray and feral dogs.

PMID- 18634474
TI  - Bait acceptability for delivery of oral rabies vaccine to free-ranging dogs on
      the Navajo and Hopi Nations.
AB  - In many areas of the world, only 30 to 50% of dogs are vaccinated against rabies.
      On some US Indian Reservations, vaccination rates may be as low as 5 to 20%. In
      2003 and 2004, we evaluated the effectiveness of commercially available baits to
      deliver oral rabies vaccine to feral and free-ranging dogs on the Navajo and Hopi
      Nations. Dogs were offered one of the following baits containing a plastic packet
      filled with placebo vaccine: vegetable shortening-based Ontario slim baits
      (Artemis Technologies, Inc.), fish-meal-crumble coated sachets (Merial, Ltd.),
      dog food polymer baits (Bait-Tek, Inc.), or fish meal polymer baits (Bait-Tek,
      Inc.). One bait was offered to each animal and its behaviour toward the bait was
      recorded. Behaviours included: bait ignored, bait swallowed whole, bait chewed
      and discarded (sachet intact), bait chewed and discarded (sachet punctured), or
      bait chewed and consumed (sachet punctured). Bait acceptance ranged from 30.7% to
      77.8% with the fish-meal-crumble coated sachets having the highest acceptance
      rate of the tested baits.

PMID- 18634475
TI  - Assessment of the efficacy of oral vaccination of livestock guardian dogs in the
      framework of oral rabies vaccination of wild canids in Israel.
AB  - Since 1956, red foxes (Vulpes vulpes) and golden jackals (Canis aureus) have been
      the primary vectors maintaining wildlife rabies in Israel. Oral rabies
      vaccination of wild canids, initiated in 1998, resulted in near-elimination of
      the disease in wildlife by 2005. In 2005 and 2006, an outbreak of rabies was
      observed in stray dogs in the vaccinated area of the Golan Heights, with no cases
      in foxes or jackals. Epidemiological investigations showed that the infected dogs
      were from territories across the border. This was confirmed by molecular
      analysis, which showed that the virus was different from rabies isolates endemic
      to this area. The objective of this study was to determine bait acceptance and
      the feasibility of oral rabies vaccination in packs of livestock guardian dogs.
      Coated sachets and fishmeal polymer baits of Raboral V-RG (Merial, USA) were
      tested in five different test zones. Both formats were hand-fed to individual
      dogs and to dogs belonging to dog packs. Bait uptake and consumption were
      observed in each dog. The estimated efficacy of oral rabies vaccination was very
      low (a maximum of 28%). Vaccine delivery problems were observed in dogs belonging
      to packs, whereby dominant animals consumed multiple baits and in competitive
      situations baits were swallowed whole. The uncertainty of oral vaccination
      necessitated turning to other methods to control this outbreak: stray dogs were
      removed and herd dogs were vaccinated parenterally. This study showed that oral
      rabies vaccination of dogs in packs using baits designed for wildlife would not
      be effective. Possibly, different baits or steps to circumvent competition within
      the pack will make this approach feasible.

PMID- 18634476
TI  - New steps in the control of canine rabies in India.
AB  - In India, about 20,000 people die of rabies every year. The dog is the main
      reservoir and transmitter of the disease. A pilot rabies control programme was
      launched in five Indian federal states in February, 2007. This initiative is led
      by the Animal Welfare Board of India (AWBI) federating many animal welfare
      organizations and the Ministry of Agriculture. It aims at creating a "Rabies Free
      India." The programme combines parenteral vaccination of accessible owned and
      stray dogs, spaying/neutering followed by parenteral vaccination and oral
      vaccination of inaccessible dogs. The freeze-dried vaccine SAG2, including the
      bait casing, was registered in India following successful evaluation of vaccine
      bait safety and efficacy (by survival after virulent challenge) in captive Indian
      stray dogs in the Bhopal High Security Animal Disease Laboratory. Furthermore,
      bait acceptance was tested under both experimental and field conditions.

PMID- 18634477
TI  - Rabies control in Mexico.
AB  - Rabies in dogs was unknown in the Americas before the arrival of the Spanish
      "Conquistadores". Until the mid-1980s rabies in animals and, in turn in humans,
      changed little from year to year, with the number of dog vaccinations reported
      annually rarely reaching one million. In Mexico, the national rabies control
      programme using mass parenteral vaccination of dogs started in 1990 with about
      seven million dogs vaccinated the same year. The number of vaccinated dogs
      exceeded 10 and 15 million in 1995 and 2005, respectively. Modern cell culture
      based inactivated rabies virus vaccines were used. A key factor for the success
      of the dog rabies control program was the supply of potent canine rabies
      vaccines. Between 1990 and 2005, more than 150 million vaccine doses from 300
      lots were administered. Each lot was tested for potency prior to use in the
      field. The required minimum content of rabies virus antigen for vaccines was 2
      IU, in accord with WHO standards. Testing revealed antigen contents ranging from
      3.28 to 5.59 IU. As a result of the mass dog vaccination campaigns, human rabies
      cases due to dog-mediated rabies decreased from 60 in 1990 to 0 in 2000. The
      number of rabies cases in dogs decreased from 3,049 in 1990 to 70 cases last
      year.

PMID- 18634478
TI  - Risk of rabies introduction by non-commercial movement of pets.
AB  - In response to a Commission request, EFSA has carried out a quantitative
      assessment of the risk of rabies introduction into the UK, Ireland, Sweden, and
      Malta due to the movement of pets incubating rabies at the time of movement. The
      risk that a pet is incubating rabies at the time of first vaccination is equal to
      the prevalence of rabies-incubating pets in the population of origin. Following
      induction of protective immunity by vaccination, animals already incubating
      rabies will still develop clinical disease as a function of time after
      vaccination (termed type A risk). A waiting period will reduce this risk. Afew
      animals may not be protected after single-shot primary vaccination. Such animals
      may become infected during the waiting period after vaccination. The risk of
      becoming infected after the first vaccination (termed type B risk) depends on the
      prevalence and efficiency of vaccination. Serological testing can be used to
      identify non-immune pets (depending on test specificity) and will therefore
      reduce this risk accordingly. The type A and B risks were modelled as a function
      of the waiting period after vaccination and fitted to a non-linear model
      incorporating vaccination efficiency and test specificity. The model can be used
      to quantify the risk of moving pets from rabies infected areas and also to
      investigate the effect of different control measures. In quantitative terms, the
      type A risk constitutes by far the major risk. Therefore, a waiting period
      (defined as the time spent between vaccination and pet movement to the destined
      country) is the major effective measure to mitigate the risk of rabies
      introduction due to an animal being infected before primo-vaccination.
      Serological testing will only add significantly to risk reduction when waiting
      periods exceed 100 days. Within the EU, the rabies prevalence in most countries
      is so low that the risk can be considered negligible. However, for some countries
      the risk is non-negligible.

PMID- 18634479
TI  - Epidemiology of rabies in Southeast Europe.
AB  - Rabies remains endemic within a number of countries in Southeast Europe including
      Romania, Bulgaria and Turkey. With the probable expansion of the European Union
      eastwards, it is likely that rabies elimination programs will be increased to
      reduce the burden of disease in new accession countries. A clear understanding of
      the epidemiology of the virus in this area of Europe is vital before such
      programs are introduced. With the exception of Turkey, the red fox (Vulpes
      vulpes) is the principal disease reservoir in Southeastern Europe. However, cases
      of rabies in the dog (Canis familiaris) are regularly reported. In contrast to
      Northern Europe, the raccoon dog (Nyctereutes procyonoides) does not appear to be
      a vector in the south. This study summarises the current rabies situation in
      Southeast Europe and demonstrates the phylogenetic relationships between the
      viruses in a number of the countries within the region. Rabies virus RNA was
      extracted from original samples and a fragment of the nucleoprotein gene
      amplified by reverse-transcriptase PCR. Automated sequencing was used to derive
      nucleoprotein gene sequences and these were used to prepare a molecular phylogeny
      of rabies viruses in Southeast Europe. In Bulgaria, the dog is the main vector
      bringing rabies into contact with humans and livestock. However, other species
      may also act as reservoirs for the disease, complicating the development of
      elimination strategies. The fox is the principal reservoir species for rabies in
      Romania although cases in dogs are regularly reported. Despite a gradual decline
      in dog rabies, urban pockets of the disease remain in many regions of Turkey.
      Furthermore, there is some evidence that the fox has been a significant vectorfor
      rabies and may be responsible for increases in rabies in cattle in the Aegean
      region of the country. Throughout the region there is evidence for cross-border
      movement of rabies by both wildlife and canine vectors.

PMID- 18634480
TI  - Rabies in the Mongolian steppes.
AB  - Historically, rabies in Mongolia has been connected to the specific steppe and
      forest-steppe landscapes, known as the Mongolian steppes. The main reservoirs of
      the rabies virus (RABV) are the wolf, red fox and corsac fox. Fox rabies has been
      reported in Mongolia since the early 1960s. Eleven human rabies cases (0.4 per
      million inhabitants) were reported in Mongolia from 1994-2004. Wild animals
      predominated as a source of human infection: five people died following wolf
      bites, two were exposed to foxes, and four to dogs. From 1996-2004, 1,273 rabid
      animals were reported (about 140 per year). Cattle consisted of more than 80% of
      all reported cases. The Mongolian steppes continue into the Chita region of
      Russia and the Republics of Buryatia, Tyva and Altai. Four RABV isolates from the
      western part of Mongolia were sequenced and compared with available isolates from
      Russia, China and other countries. The isolates from Mongolia belonged to the
      "steppe" phylogenetic clade, which includes viruses circulating in vast
      territories, from Southeast Europe to Tyva, West Siberia and Kazakhstan. However,
      RABV isolates from Mongolian-type steppes in the east (Chita region, Russia)
      belong to the eastern group of arctic-like viruses.

PMID- 18634481
TI  - Epidemiology and control of rabies in Iran.
AB  - Rabies is endemic in Iran. It is the most important zoonotic disease in the
      country. Based on studies undertaken during the past few decades, there is
      evidence that the main reservoir for rabies is wolves. The incidence of rabies in
      humans and animals is increasing each year. In 2006, more than 130,000 people
      received post-exposure prophylaxis. Similar figures apply regarding preventive
      vaccination in animals. Official data suggest that the majority of human
      exposures are due to biting episodes caused by dogs. However, investigations
      performed by this team showed that in many cases wolves were responsible for
      rabies transmission to humans. Because of the potential feasibility of oral
      rabies vaccination, this team has proposed a pilot study to evaluate the use of
      an oral rabies vaccine for vaccination of wildlife to control rabies in Iran.

PMID- 18634482
TI  - Rabies risk in raccoon dogs and foxes.
AB  - Raccoon dogs are seen as a new host for fox rabies in Europe. Disease spread in a
      community of species can change the epidemiology of the disease and calls for new
      disease control strategies. This study assesses the risk of a rabies outbreak,
      introduced to a community of foxes and raccoon dogs in Southern Finland, as an
      example of the reintroduction of rabies into rabies-free areas. Epidemiology is
      simulated with a two-species model, based on approaches for rabies in foxes and
      parameterised from recently published data on raccoon dog and fox ecology in
      Northeast Europe. The risk of the establishment of rabies was investigated. The
      effectiveness of vaccination control was estimated. Results show that rabies may
      not spread in a single species, when population densities are low, as in Finland.
      However, persistent epidemics are very likely in the species' community. The
      threshold density for a system of combined species decreases non-linearly,
      compared to the thresholds of each of the species. A behavioural factor that
      influences rabies epidemiology is raccoon dog hibernation, which may alter with
      climate change. Thus, the new host, the raccoon dog, has to be considered in
      defining new emergency control strategies for rabies free states in Europe.

PMID- 18634483
TI  - Downside risk of wildlife translocation.
AB  - Translocation has been used successfully by wildlife professionals to enhance or
      reintroduce populations of rare or extirpated wildlife, provide hunting or
      wildlife viewing opportunities, farm wild game, and reduce local human-wildlife
      conflicts. However, accidental and intentional translocations may have multiple
      unintended negative consequences, including increased stress and mortality of
      relocated animals, negative impacts on resident animals at release sites,
      increased conflicts with human interests, and the spread of diseases. Many
      wildlife professionals now question the practice of translocation, particularly
      in light of the need to contain or eliminate high profile, economically important
      wildlife diseases and because using this technique may jeopardize international
      wildlife disease management initiatives to control rabies in raccoons, coyotes,
      and foxes in North America. Incidents have been documented where specific rabies
      variants (Texas gray fox, canine variant in coyotes, and raccoon) have been moved
      well beyond their current range as a result of translocation, including the
      emergence of raccoon rabies in the eastern United States. Here, we review and
      discuss the substantial challenges of curtailing translocation in the USA,
      focusing on movement of animals by the public, nuisance wildlife control
      operators, and wildlife rehabilitators.

PMID- 18634484
TI  - Finnish-Russian programme for the control of rabies (2005-2010).
AB  - The Finnish-Russian collaboration on rabies control began in 2000. This data
      summarizes the results of the scientific part of the programme, including rabies
      monitoring in Russia and the molecular epidemiological studies with field
      viruses.

PMID- 18634485
TI  - The rabies elimination programme in Estonia using oral rabies vaccination of
      wildlife: preliminary results.
AB  - The first case of sylvatic rabies in Estonia was recorded in 1968. Rabies is
      maintained in raccoon dogs and red foxes. The main prophylactic means used in
      animals up to 2005 consisted of compulsory vaccination of dogs and cats. In
      October 2005, the first large scale wildlife oral vaccination campaign was
      carried out in the northern part of the country (25,800 km2) from the western to
      the eastern border, including islands. In 2006, two campaigns were conducted
      across the country. Rabies surveillance and the efficacy of oral vaccination were
      assessed by a follow-up of rabies incidence and bait consumption (tetracycline
      examination). As a result, the number of rabies cases decreased drastically in
      2005 and 2006 with a total of 266 and 114 animal cases, respectively. These
      results will be discussed in the context of rabies epidemiological surveillance
      in Estonia and in Europe.

PMID- 18634486
TI  - Rabies surveillance in Poland (1992-2006).
AB  - Data on the surveillance of rabies in Poland from 1992 to 2006 is presented.
      Between 1992 and 2006, 22,575 rabies cases were diagnosed. There were 3,963
      (17.5%) cases recorded in domestic animals, 18,555 (82.2%) in wildlife and 57
      (0.3%) in bats. The peak of the epizootic in wildlife was recorded in 1992 with
      3,084 cases. There were 2,547 cases recorded in wildlife with 2,079 (81.6%) found
      in the red fox. In 1993, the decision was made to apply oral rabies vaccination
      (ORV) of the red fox as a method of rabies control. The programme was started in
      western part of Poland, which borders Germany, and extended eastward in the
      following years. ORV was undertaken twice peryear (spring and autumn). In 2002,
      the vaccine campaign covered the whole territory of Poland. After 13 years of
      ORV, rabies incidence decreased sharply, from 3,084 cases in 1992 to 82 in 2006
      (a 97% decrease in the number of rabies cases). The epidemiological situation in
      2006 points to the constant decrease of rabies cases as a result of ORV. The red
      fox remains the main reservoir of rabies. The progress made over the past decade
      demonstrates that Poland is meeting the requirements to eliminate rabies in
      terrestrial animals.

PMID- 18634487
TI  - Efficacy of a square presentation of V-RG vaccine baits in red fox, domestic dog
      and raccoon dog.
AB  - Oral vaccination programmes conducted in rabies infected countries from Eastern
      Europe and Eurasia should not be restricted to foxes but should target other
      major rabies vectors such as dogs and raccoon dogs as well. The objective of this
      experimental trial was to assess the protection induced by the vaccine by
      challenging these different species, which had been previously vaccinated
      intramuscularly with the square V-RG baits (produced in the US). Different
      parameters were evaluated such as attractiveness of the baits and induction of
      neutralising antibodies as an indicator for immunogenicity and protection after
      rabies challenge. The acceptability of the square bait was satisfactory in dogs,
      foxes and raccoon dogs, confirming previous laboratory and field studies
      conducted with the rectangular baits. Only one vaccinated dog out of nine
      seroconverted after vaccination and among them one dog died of rabies. Eight of
      ten vaccinated foxes seroconverted after vaccination and survived the rabies
      challenge. All vaccinated raccoon dogs seroconverted after challenge and all
      survived the challenge. These trials demonstrated that the square presentation of
      the V-RG vaccine was attractive, immunogenic and efficacious.

PMID- 18634488
TI  - Scenario-analysis evaluating semergency strategies after rabies re-introduction.
AB  - Now that the elimination of rabies in Western Europe is nearly complete, thanks
      to the oral mass vaccination of foxes (ORV) which took place over the last 25
      years, it is necessary to prepare for emergency situations due to the re
      introduction of rabies from still infected areas. Such emergency strategies
      should aim at minimizing the risk of falling back to large-scale vaccination, in
      a cost efficient manner. An approved spatially-explicit simulation model of
      spread and control of rabies was adapted to the new problem of re-introduction of
      rabies into free areas. The logic of the model and options for local emergency
      vaccination (for example ring-vaccination vs. compact area treatment or heavily
      concentrated vs. thin extended control areas) were determined. Based on
      systematic simulation experiments the performance of strategic options was
      assessed. Key issues such as public health risk (i.e. number of rabies cases),
      failure risk (i.e. disease breakout from the control area), and budgetary risk
      (i.e. duration of the emergency program) were simultaneously considered. The
      results obtained reveal efficiency relations that contradict a priori derived
      management suggestions.

PMID- 18634489
TI  - The financial challenge of keeping a large region rabies-free--the EU example.
AB  - Following the implementation of oral rabies vaccination of foxes (ORV) in Western
      Europe, a continuous decrease in rabies incidence was reported, and eventually
      rabies was eliminated. Once fox rabies is eliminated in a given area, re
      infection from neighbouring infected countries is a permanent threat. As a
      result, countries need to maintain a vaccination belt along common borders until
      rabies is also eliminated in sufficiently large border regions of neighbouring
      infected countries. In a theoretical approach EU member states were taken as a
      prime example, assuming that they were rabies-free but that neighbouring
      countries were still infected. Using GIS, a 50 km deep vaccination belt beyond
      the front of the rabies endemic zone was installed in countries bordering those
      regions. The annual cost for the prevention of re-infection of the EU territory
      was calculated considering current EU recommendations (vaccination twice per
      year, aerial and complementary hand distribution, bait density of 30 baits per
      km2). Minimum and maximum prices for commercial available oral rabies vaccine
      baits, aircraft and rabies surveillance were considered for the calculation of
      costs. The total vaccination area which needed to be established was about
      251,000 km2. Using mainly fixed-wing aircraft, the annual cost for ORV including
      rabies surveillance varied between a minimum of 10 and a maximum of 16M Euro,
      depending on the cost of vaccine bait. If helicopters were used exclusively, the
      maximum cost increased to about 32M Euro. Depending on the length of the border
      to infected regions, countries will have to pay up to 25% of the total cost.
      Countries which need to install a vaccination belt will never have a rabies-free
      status because of the likely occurrence of rabies cases in border zones.

PMID- 18634490
TI  - What is the future of wildlife rabies control in Europe?
AB  - Over the last fifteen years or so, classical rabies in terrestrial wildlife has
      been eliminated from large areas of Western Europe. Over the next few years,
      terrestrial rabies is likely to occur only east of a line from the Baltic Sea to
      the Black Sea; the overall aim is to eliminate terrestrial rabies from the whole
      European Union. Elimination of rabies from the less rich countries of Eastern
      Europe, and the protection of Europe against a resurgence of rabies in the longer
      term requires modifications to existing OIE and WHO strategies. Here we discuss
      the options available to eliminate rabies in wildlife while taking account of
      financial cost, and how to maintain a 'cordon sanitaire' along the eastern
      boundary of the EU in order to protect the rabies-free areas from rabies
      incursion. Minimising financial costs at the national level is obviously
      essential, considering the competing priorities for development and health. This
      could be achieved either by increasing external funding (for example by the EU)
      and/or by changing the currently agreed vaccination strategy to reduce costs; any
      such change must not substantially reduce the chances of rabies elimination. A
      cordon sanitaire might be placed outside the economic area of the EU, to protect
      the whole of the EU, or it might be placed within the easternmost countries to
      ensure logistical consistency of vaccination. Policy must also anticipate an
      emergency due to rabies breaking out in a previously freed region. Strategic
      planning may be complicated by the increasing range and abundance of the raccoon
      dog, an introduced species that is increasingly important as a host for fox
      rabies. It is argued here that models help to evaluate altemative strategies,
      exploring options for optimising costs by minimising bait density and frequency
      or by reducing the vaccination area.

PMID- 18634491
TI  - The strength of 70%: revision of a standard threshold of rabies control.
AB  - The success of oral vaccination of foxes (ORV) conceptually is linked to the
      immunisation of host individuals beyond the herd immunity threshold. However,
      field evidence and theoretical analysis suggests that mathematically derived
      values of herd immunity might be rather conservative and, moreover, restrict the
      adjustment of standard ORV protocols in the case of limited resources. Here, the
      relationship between baiting effort, duration of ORV programmes and rabies
      elimination is analysed. An individual-based, spatially explicit model for the
      control of rabies in foxes that incorporates the important peculiarities of the
      vaccination process, i.e. the spatial distribution of infected hosts, irregular
      home-range use, heterogeneous bait coverage etc., is applied. Using multiple
      repetitions of simulated ORV programmes, the control outcome is analysed in a
      chance-like fashion overriding the yes-or-no prediction inherent in the herd
      immunity concept. It is shown why control planning must not only aim at
      particular immunisation levels but, simultaneously, has to specify the allowed
      time horizon of control success. It is demonstrated that planning a higher chance
      of elimination increases necessary effort non-linearly. It was found that low
      immunisation results (i.e. 50%) still provide a reasonable chance of control
      success. The potential changes in ORV planning and evaluation allowing for the
      integration of risk concepts in strategies are discussed.

PMID- 18634492
TI  - A random grid based molecular epidemiological study on EBLV isolates from
      Germany.
AB  - Germany has reported one of the highest levels of EBLV cases in bats in Europe.
      So far, all isolates originating from Germany have been identified as EBLV-1,
      using monoclonal antibodies, and a preliminary epidemiological study has
      indicated that there is a distinct geographical distribution of EBLV-1 in
      Germany. To further investigate the spatial and temporal distribution of EBLV-1
      variants in Germany and their impact on molecular epidemiology, isolates were
      selected using a random grid sampling procedure based on GIS. Agrid layer 30 km
      long over the entire area of Germany was applied to 120 geo-referenced isolates
      and one isolate of each grid cell containing EBLV isolates was randomly chosen.
      Once selected, the nucleoprotein (N) plus parts of the phosphoprotein (P) gene of
      each isolate were sequenced using direct cycle sequencing. Results of the
      subsequent phylogenetic analysis of the N-gene confirmed previous studies on
      European EBLVs, showing a high sequence homology between German EBLV-1 isolates.
      Almost identical sequence homologies within certain geographical regions indicate
      genomic stability during the transmission cycle of EBLV-1, with little geographic
      spread or intermixing. Interestingly, a 6 bp insertion as well as a single
      nucleotide insertion, detected in the N-P intergenic region, has been found in
      EBLV-1 isolates from Germany.

PMID- 18634493
TI  - Asymptomatic rhabdovirus infection in meridional serotine bats (Eptesicus
      isabellinus) from Spain.
AB  - Different rhabdoviruses have been found in healthy bats, suggesting asymptomatic
      infection. The aim of this study was to focus on the epidemiology and
      pathogenesis of EBLV1 infection in the meridional serotine bat (Eptesicus
      isabellinus), as well as to search for other rhabdoviruses in this bat, which is
      the responsible for more than 95% of cases of human exposure to lyssaviruses in
      Europe. RT-PCR on oropharyngeal swabs was used together with antibody detection
      by the Rapid Fluorescent Focus Inhibition Test (RFFIT) to investigate EBLV1
      circulation in 19 natural colonies of meridional serotine bats in Andalusia
      (Spain) from 1998 to 2003. The survey was based on 1,227 different captures of
      1,033 individuals that were ring banded, sampled and released. Individuals that
      were repeatedly captured were always found in the same colony, despite the fact
      that some colonies were less than five km apart. Viral circulation was detected
      in ten colonies either by RT-PCR, serology or both. Each colony showed a
      different temporal pattern of viral circulation suggesting independent endemic
      circulation. Some positive individuals were captured healthy in following
      campaigns providing evidence for survival after viral infection. RNA from two
      apparently new Dimarhabdoviruses was also found in the pharyngeal cavity of two
      healthy bats.

PMID- 18634494
TI  - Epidemiology and pathogenicity of African bat lyssaviruses.
AB  - Lyssaviruses belonging to all four known African Lyssavirus genotypes (gts) have
      been reported and isolated from SouthAfrica over the past few decades. These are:
      (1) Duvenhage virus (gt4), isolated again in 2006 from a human fatality; (2)
      Mokola virus (gt3), isolated irregularly, mostly from cats; (3) Lagos bat virus
      (gt2) continually isolated over the past four years from Epomophorus fruit bats
      and from incidental terrestrial animals and (4) Rabies virus (gt1) - with two
      virus biotypes endemic in mongoose and in canid species (mostly domestic dogs,
      jackals and bat-eared foxes), respectively. Only two of these are associated with
      bats in Southern Africa, viz. Duvenhage virus and Lagos bat virus (gts 4 and 2).
      For both these genotypes the authors have embarked on a programme of comparative
      study of molecular epidemiology. Duvenhage virus nucleoprotein nucleotide
      sequence analysis indicated a very low nucleotide diversity even though isolates
      were isolated decades apart. In contrast, individual isolates of Lagos bat virus
      were found to differ significantly with respectto nucleoprotein gene nucleotide
      sequence diversity as well as in pathogenicity profiles.

PMID- 18634495
TI  - Experimental infection of big brown bats (Eptesicus fuscus) with West Caucasian
      bat virus (WCBV).
AB  - Big brown bats (Eptesicus fuscus), either recently captured individuals or
      survivors from previous experimental infection with Irkut virus (IRKV), were
      inoculated with West Caucasian bat virus (WCBV), intramuscularly into the
      masseter (n=7) or neck (n=8) muscles, or orally (n=6). Three bats inoculated into
      the neck muscles developed rabies and died between days 10 and 18. Viral RNA was
      detected in a number of tissues but isolation was successful only from the brain.
      An oral swab of one of these bats was also PCR-positive, but the isolation
      attempt failed. Brains, salivary glands and swabs from the survivors (six months
      observation) were negative, as well as all blood pellets collected. Therefore, no
      suggestions for a carrier state or viremia were obtained. In four surviving bats
      inoculated in the masseter muscles, WCBV-neutralizing antibodies were detected up
      to the end of experiment. The absence of antibodies in the three rabid bats may
      be the result of shorter incubation periods. Bats infected orally neither died
      nor responded serologically. In the bats previously infected with IRKV, IRKV
      neutralizing antibodies were detected as well, up to the end of observation (12
      months after IRKV challenge), even if they were not boosted by WCBV inoculation.

PMID- 18634496
TI  - Experimental infection of foxes with European bat lyssaviruses type-1 and -2.
AB  - Experimental studies have been undertaken to assess the susceptibility of silver
      foxes to bat variants of rabies virus, namely European Bat Lyssaviruses (EBLVs).
      Both EBLV-1 and EBLV-2 have been isolated in European bats since 1954, in
      Eptesicus serotinus and Myotis species, respectively. Since 2000, the number of
      reported cases has increased largely due to the improvement of the surveillance
      of bat rabies virus throughout Europe. Although over >800 EBLVs cases have been
      reported in bats in Europe, EBLV-1 and -2 viruses are rarely reported to infect
      humans and terrestrial animals. The study presented here shows that the
      sensitivity of silver foxes is low when infected with EBLVs via the intramuscular
      route; in contrast all animals infected via intracranial inoculation succumbed to
      the experimental challenge. The mortality rate was 100% for both EBLV-1
      (approximately 4.5 log) and EBLV-2 (approximately 3.0 log). This data suggests
      that the susceptibility of foxes to EBLV-1 and EBLV-2 is low and that the
      transmission (spillover) and adaptation of EBLVs from a bat to a fox may be
      theoretically possible but unlikely.

PMID- 18634497
TI  - The application of genetic markers for EBLV surveillance in European bat species.
AB  - The United Kingdom has performed passive surveillance for European bat
      lyssaviruses (EBLVs) since 1987, and species-targeted surveillance since 2003.
      One critical component of these studies is the accurate identification of bats
      either submitted for testing or sampled in the field. Identification is dependent
      on numerous morphological characteristics. Whilst this is an effective means of
      bat identification, a number of problems remain with this approach. It relies on
      the experience of bat specialists and can lead to problems in differentiating
      members of the Myotis genus, particularly between Myotis mystacinus (whiskered
      bat) and Myotis brandtii (Brandt's bat), and between the most common species of
      the genus Pipistrellus. Furthermore, degradation of bats submitted for testing
      can also lead to problems in making an accurate species identification.
      Comparison of genetic sequence data could offer an alternative approach to
      differentiating bat species when morphological characterisation is not possible.
      Using tissue samples from UK resident bat species, sequence analysis of the
      mitochondrial DNA cytochrome b gene, and the beta-actin gene allowed for
      identification of many of the most common bat species in the UK, and genetic
      separation of two morphologically cryptic species. Application of this approach
      identified the species of a bat infected with EBLV-2 in Surrey as Myotis
      daubentoni (Daubenton's bat).

PMID- 18634498
TI  - Generalised cranial artery spasm in human rabies.
AB  - In 2004, a teenager survived bat-associated rabies through the Milwaukee protocol
      (MP). This survivor and another patient with dog-associated rabies were found to
      have developed deficiencies of tetrahydrobiopterin (BH4) and associated
      neurotransmitters. BH4 is also essential for neuronal nitric oxide synthase
      (nNOS), so rabies is predicted to cause constriction of cerebral arteries. We
      assume that rabies virus, which almost exclusively targets neurons, would
      disproportionately affect cerebral over systemic perfusion by disrupting nNOS and
      lead to generalised cerebral artery spasm. Cranial artery vasospasm, therefore,
      was actively sought in two rabies patients, with the intention to specifically
      treat with BH4 and L-arginine when necessary. Flow velocities and resistive (RI)
      or pulsatility indices (PI) of middle cerebral arteries (MCA) were obtained by
      transcranial doppler ultrasound (TCD). A survival analysis of 8 attempts at the
      MP is presented. Of these, two cases are reported here. The first case is one
      child with bat-associated rabies who developed severe bilateral MCAspasm on
      hospital day (HD)-10 that responded to very low dose (0.2 mcg/kg/min)
      nitroprusside. The second case, a child with dog-associated rabies, developed
      spasm of MCA on HD-6 that responded to 6 mg/kg/day BH4. A second spasm with high
      RI (without cerebral oedema or increased intracranial pressure) responded to 20
      mg/kg/day BH4 and 0.5 g/kg/dose L-arginine. Review of the TCD of the first child
      showed a similar second spasm seven days after first episode. Cerebral artery
      vasospasm occurred in the two children with rabies, but was clinically silent by
      standard monitoring. Spasm responded to drugs directed at the NOS pathway. Animal
      models for treatment of rabies are sorely needed to evaluate therapy.

PMID- 18634499
TI  - Human rabies therapy: lessons learned from experimental studies in mouse models.
AB  - Ketamine was one of the therapeutic agents used as a therapy for a human rabies
      survivor who did not receive rabies vaccine. Ketamine therapy is re-examined here
      in infected mouse primary neuron cultures and in adult ICR mice using the CVS
      strain with both intracerebral and peripheral routes of inoculation with ketamine
      vs. vehicle given intraperitoneally. No significant beneficial therapeutic
      effects of ketamine in the cultures or mouse model were observed. This team does
      not recommend further widespread clinical use of ketamine on human rabies
      patients until further experimental work demonstrates therapeutic efficacy.
      Because of the potential neuroprotective and anti-apoptotic properties of
      minocycline, minocycline therapy was assessed in infected primary neuron cultures
      and in neonatal ICR mice infected by peripheral inoculation with a highly
      attenuated rabies virus strain. No beneficial effect of minocycline was observed
      in the primary neuron cultures. In the mouse model, minocycline therapy
      aggravated the clinical neurological disease and resulted in higher mortality. An
      anti-apoptotic effect of minocycline was noted in the brains of infected mice,
      which may have very mildly increased viral spread. An anti-inflammatory effect
      was also noted in the brain using a CD3 T cell marker. These effects likely
      aggravated the disease. This team recommends that empirical therapy with
      minocycline be avoided in the management of rabies and viral encephalitis in
      humans until more information becomes available.

PMID- 18634500
TI  - Rabies control and prevention in Georgia: current status and perspectives.
AB  - The incidence of rabies post-exposure prophylaxis (PEP) is very high in Georgia,
      at 876/100,000 persons in 2006. Data from the National Centre for Disease Control
      on rabies surveillance for 2004, 2005 and 2006 was analysed, with the objective
      of improving postexposure policy and practice, as well as identifying priorities
      for national surveillance and control. For the base period 1986-1995, a total of
      40 rabies cases in humans were reported in Georgia. In 2004, 2005 and 2006 there
      were 12, 10 and 7 reported cases, respectively, representing a significant
      increase in overall incidence for this period. Ninety-three percent (93%) of
      cases were caused by dog bites. The large population of stray dogs and
      unvaccinated pets in Georgia is recognized as the main risk factor. In 2006,
      38,569 patients received PEP following bites by an animal with suspected rabies,
      compared to 23,712 in 2004, and 30,254 in 2005 (representing a 1/3 increase
      annually). Of the total number of PEP treatments initiated in 2004, 16,568(69.9%)
      were discontinued due to the fact that the biting animal remained healthy during
      the observation period; 23,106 (76.4%) were discontinued in 2005; and 30,254
      (78.4%) were discontinued in 2006. Concerns regarding the safety of available
      immunoglobulins, uncertainty regarding the use of vaccines and immunoglobulins
      from different manufacturers, and the inconsistency of national guidelines with
      international recommendations are cited as obstacles to an improved delivery of
      PEP. For the effective control of rabies, the national veterinary programmes need
      to be improved, stray dog population control measures need to be updated
      according to international standards, and clear national guidelines regarding the
      use of rabies vaccines and immunoglobulins for PEP should be developed and
      implemented.

PMID- 18634501
TI  - One or three intradermal injections within one week for rabies pre-exposure
      immunization.
AB  - Pre-exposure rabies vaccination is recommended fortravellers to endemic countries
      and forselected populations in highly endemic regions. It consists of three
      injections administered over 3-4 weeks. Travellers often ignore or do not have
      enough time to receive a complete course prior to departure or leave with only
      one or two injections. In this study, the secondary antibody response in
      volunteers who received one or three injections within one week is evaluated.
      Results are compared to the recommended three injection regimen when administered
      with two booster vaccinations on days 0 and 3 one year later. Long-lasting immune
      memory in volunteers who received only one time vaccination of 0.1 ml (1 site)
      intradermally and then received two booster vaccinations of 0.1 ml (1 site)
      intradermally on days 0 and 3, one or three years later is also reported. All
      volunteers developed an accelerated and adequate neutralizing antibody response
      within seven days after they received two boosters. These data suggest that three
      injections within one week are as immunogenic as three injections within four
      weeks. One clinic visit with two-site 0.1 ml ID injections or a one-site single
      0.1 ml pre-exposure rabies vaccination is enough to prime the host immune memory
      for at least one to three years.

PMID- 18634502
TI  - Epidemiology and prophylaxis of rabies in humans in France: evaluation and
      perspectives of a twenty-five year surveillance programme.
AB  - The National Reference Centre for Rabies (NRC) was created at the Pasteur
      Institute after the fox epizootic reached the French territory. The missions of
      the NRC include, among others, the surveillance of rabies cases in humans and
      rabies post-exposure prophylaxis (PEP) treatments. The surveillance has been
      effective since 1982. A Bulletin on the Epidemiology and the Prophylaxis of
      Rabies in Humans in France is published every year. This Bulletin is now
      available on the Internet for Human Health and Veterinary national and local
      Authorities. Since 2005, data is collected with new software, Voozanoo, directly
      via the Internet. Twenty cases of rabies in humans have been reported since 1970.
      There were no indigenously acquired cases. The number of PEP treatments peaked in
      1990, when the number of cases in the wild fauna was at its acme. Following the
      decrease of rabies cases in the wild fauna, PEP decreased by 60%. Nevertheless,
      about4,000 PEP treatments are still carried out. These patients have been exposed
      to bats or to rabid animals illegally introduced onto the French territory, or
      during a stay in rabies enzootic countries, or to unobservable animals. The study
      of this database leads to a number of conclusions: canine variants acquired
      directly in canine enzootic areas, that are translocated, or acquired through
      iatrogenic exposure, are responsible for the majority of cases; bats appear to be
      an increasing source of exposure; PEP surveillance is of utmost importance to
      monitor and to improve the quality of case management.

PMID- 18634503
TI  - Immune evasion, a critical strategy for rabies virus.
AB  - It is intriguing to note that RABV progression is interrupted neither by
      destruction of the infected neuron nor by the immune response. Thus, it is likely
      that RABV has developed a subversive strategy to avoid functional neuron
      impairment, which compromises the infectious cycle. Rabies virus
      neuroinvasiveness results from two factors: not only does neurotropic rabies
      virus avoid inducing neuronal cell death, but also 'protective' T cells that
      migrate into the infected nervous system are killed by apoptosis or inactivated,
      as a result of the overexpression of immunosubversive molecules such as FasL, HLA
      G or B7-H1 in the infected nervous system. This suggests that the preservation of
      the neuronal network and the destruction of T cells that invade the nervous
      system in response to the infection are crucial events for rabies virus
      neuroinvasion and for transmission of rabies virus to another animal.
      Implications of these findings for rabies treatment are discussed.

PMID- 18634504
TI  - BHK-21 cell culture rabies vaccine: immunogenicity of a candidate vaccine for
      humans.
AB  - Veterinary rabies vaccines produced in BHK-21/C13 permanent cell cultures have
      been used for a long period of time and have been proven as efficacious and safe.
      A candidate vaccine for human use (YU BHK Rabivak) was developed at the Pasteur
      Institute, Novi Sad, Serbia on the basis of the fixed rabies virus strain "L.
      Pasteur 2061/Vero 15 pas" using BHK 21/C13 as a cell substrate for vaccine
      production. To test the vaccine immunogenicity, a clinical trial was conducted
      involving 164 subjects between 18 and 60 years of age, immunized either with the
      YU BHK Rabivak vaccine candidate orwith a commercially available vaccine
      (Rabipur). Three groups of subjects were immunized with either vaccine by
      intramuscular administration in the deltoid region, following a pre-exposure
      regimen on days 0, 7 and 21, or the Essen or Zagreb post-exposure regimens.
      Rabies virus neutralizing antibodies (VNA) titres were determined by rapid
      fluorescent focus inhibition test (RFFIT) 21 and 30-45 days post vaccination. A
      protective titre of VNAs (>0.5 IU/ml) was found in all subjects vaccinated.
      Dynamics of the immune response showed that 96.4% of the subjects developed
      protective VNA titres after two doses, 99.3% after three doses and 100% after
      four and five doses of the candidate YU BHK Rabivak vaccine. There was a low
      reactogenicity without serious adverse events indicating a satisfactory safety
      profile in humans. Results obtained in this study indicate that BHK 21 cells
      offer the possibility of producing an efficacious and safe cell-culture rabies
      vaccine for humane use.

PMID- 18634505
TI  - Factors influencing the antibody response to vaccination against rabies.
AB  - Preventive vaccination against rabies virus is a highly effective method for
      preventing rabies in humans and animals. For travel purposes, vaccination of
      domestic carnivores is obligatory. In addition, some countries require testing
      for neutralizing antibodies against rabies. The minimal threshold level accepted
      by WHO/OIE is 0.5 IU/ml. Despite proper vaccination some animals do not reach the
      threshold. The objective of this study was to identify specific risk factors in
      dogs and cats for post-vaccination rabies antibody titres below 0.5 IU/ml by FAVN
      test. Rabies vaccination protocols and recommendations were reviewed with regard
      to travel regulations. Comprehensive data was collected on animals tested for
      rabies antibodies via a questionnaire sent to veterinarians who submitted sera
      for rabies titration. The questionnaire included data on species, age, sex,
      breed, vaccine used, date of last vaccination and blood sampling, vaccination
      history and further medical treatments at time of vaccination. Data on around
      1,200 animals was analysed. Most animals older than one year had already received
      more than one rabies vaccination. The influence of breed and sex on antibody
      titre seems to be insignificant. Young dogs have a high risk of results below 0.5
      IU/ml after their first vaccination. This risk can be minimised by the
      application of a second vaccination and blood sampling according to the
      manufacturer's recommendations. An important factor for the test outcome might be
      the virus strain used in the vaccine.

PMID- 18634506
TI  - Attaining raccoon rabies management goals: history and challenges.
AB  - Prior to 1977, raccoon (Procyon lotor) rabies was confined to the southeastern
      US. Translocations led to emergence of this rabies variant in the mid-Atlantic
      states, followed by spread northerly to northeast Ohio and Ontario, Quebec, and
      New Brunswick, Canada. Raccoon rabies is currently contiguous from southwest
      Alabama to southeastern Canada. Since 1998, state, federal, county and municipal
      as well as Canadian and Mexican experts have collaborated on goals and strategies
      to prevent raccoon rabies spread in North America. Coordinated programmes have
      been established from Maine to Alabama. Successes have been realized through
      strategies that rely heavily on oral vaccination. International coordination
      targeting raccoon rabies continues in eastern Canada, where contingency actions
      have led to elimination or near elimination in Ontario and New Brunswick.
      However, increasingly, focus in the US has been directed toward contingency
      actions to "hold-the-line" where raccoon rabies threatens to spread to new areas,
      rather than on raccoon rabies elimination. We report on the challenges of
      achieving enhanced rabies surveillance, containment of raccoon rabies, and local
      elimination of raccoon rabies, as well as the need for international coordination
      in meeting these challenges.

PMID- 18634507
TI  - Intake and stability of a rabies vaccine.
AB  - The intake and stability of rabies vaccine baits were studied over a two week
      period under field conditions. High intake of vaccine baits was observed in the
      spring and autumn. In the spring, the intake of vaccine baits lasted almost two
      weeks while in the autumn vaccine baits were consumed over the first days
      following distribution. Differences in bait stability were observed after
      exposure to ambient temperatures. Baits were more stable in a forest environment
      than on the edge of a forest. Deformation and disintegration of bait casing
      occurred with some baits at the beginning of trial. Rainy weather was probably
      detrimental to bait casing stability. Vaccine titres were stable for nine days in
      the forest and six days on the edge of a forest in the spring, while results of
      the study make it possible to predict that vaccine titres may have decreased
      rapidly in the autumn. Laboratory results on bait stability were different from
      those obtained in the field.

PMID- 18634508
TI  - Immunogenicity of the ERA G 333 rabies virus strain in foxes and raccoon dogs.
AB  - The immunogenic properties of ERA G 333 attenuated rabies virus strain in foxes
      and raccoon dogs by the oral route of administration were examined. This strain
      is a proposed candidate for oral rabies vaccine in Russia. As was previously
      demonstrated, the advantage of this virus, provided by the US Centers for Disease
      Control and Prevention in the framework of the Biotechnology Engagement Program,
      is apathogenicity for 3-week old and adult mice, as well as for other target and
      non-target species, even when challenged via the intracerebral route. A group of
      12, 7-8 month-old foxes and eight wild captured raccoon dogs were given 2.0 ml of
      ERA G 333 (titre 107.5 FFU) orally on the tongue. Another three foxes and three
      raccoon dogs were retained as controls. Blood samples were collected before
      immunization and on day 60 thereafter. The antibody titres were determined by the
      fluorescent antibody virus neutralization (FAVN) test. Eight foxes and three
      raccoon dogs showed seroconversion on day 60 postvaccination. Eleven foxes and
      four raccoon dogs survived challenge with a virulent rabies virus strain. This
      study has demonstrated the possibility of using ERA G 333 for the oral
      vaccination of red foxes and raccoon dogs. Further experiments are needed to
      determine the effective dose, virus stability, and the strength and duration of
      immunity.

PMID- 18634509
TI  - Canine adenovirus based rabies vaccines.
AB  - Adenovirus based vectors are very attractive candidates for vaccination purposes
      as they induce in mammalian hosts potent humoral, mucosal and cellular immune
      responses to antigens encoded by the inserted genes. We have generated E1-deleted
      and replication-competent recombinant canine type-2 adenoviruses expressing the
      rabies virus glycoprotein (G). The effectiveness of both vectors to express a
      native G protein has been characterized in vitro in permissive cell lines. We
      compared the humoral and cellular immune responses induced in mice by
      intramuscular injection of the recombinant canine adenovirus vectors with those
      induced by a human (Ad5) E1-deleted virus expressing the same rabies G protein.
      Humoral responses specific to the adenoviruses or the rabies glycoprotein
      antigens were studied. The influence of the mouse strain was observed using
      replication-competent canine adenovirus. A high level of rabies neutralizing
      antibody was observed upon i.m. inoculation, and 100% of mice survived lethal
      challenge. These results are very promising in the perspective of oral vaccine
      for dog rabies control.

PMID- 18634510
TI  - Development of an edible rabies vaccine in maize using the Vnukovo strain.
AB  - The objective of this study was to obtain transgenic maize expressing the rabies
      virus glycoprotein (G) of the Vnukovo strain and to evaluate its immunogenicity
      in mice, by the oral route. The ubiquitin maize promoter fused to the whole
      coding region of the rabies virus G gene, and a constitutive promoter from
      cauliflowermosaic virus (CaMV)were used. Maize embryogenic callus were
      transformed with the above construct by biolistics. Regenerated maize plants were
      recovered and grown in a greenhouse. The presence of the G gene and its product
      was detected by PCR and western blot, respectively. The amount of G protein
      detected in the grains was approximately 1% of the total soluble plant protein.
      Transformed kernels containing 50 microg of G protein were given once by the oral
      route in adult mice (BALB-C strain). Challenge was undertaken at 90-days post
      vaccination using a lethal dose of a vampire bat rabies virus (100 LD 50% in
      mice); vampire bats are one of the main reservoirs in Latin America. The edible
      vaccine induced viral neutralizing antibodies (VNA) which, protected mice 100%
      against challenge. The control group did not survive. The G protein of the
      Vnukovo strain expressed in transgenic maize may be considered as an oral
      immunogen against rabies, conferring cross-protection.

PMID- 18634511
TI  - Genetically engineered colorimetric single-chain antibody fusion protein for
      rapid diagnosis of rabies virus.
AB  - The most widely used test for rabies diagnostics is the fluorescent antibody
      test, which is recommended by both the World Health Organization and the World
      Organisation for Animal Health (OIE). This test may be used directly on a smear,
      and can also be used to confirm the presence of rabies antigen in cell culture or
      in brain tissue for diagnosis. The colorimetric enzymes are usually coupled to an
      antibody by chemical means using cross-linking reagents. However, such non
      specific procedures lead to heterogeneous conjugates, sometimes with reduced
      activity and specificity. To bypass these problems, genetic engineering has
      provided a way to create chimeric bifunctional molecules in which the variable
      domains of an antibody are genetically linked to unrelated protein tracers. In
      this study, we describe the successful production of a bifunctional chimeric
      protein based on alkaline phosphatase-fused anti-rabies virus glycoprotein scFv
      antibody fragment. We also report the antigen binding properties and the alkaline
      phosphatase activity of the recombinant conjugate protein. We established its
      value as a novel in vitro tool for detecting the rabies virus in brain smear in a
      one-step procedure; it presents a similar sensitivity and specificity to that
      obtained using standard reagents.

PMID- 18634512
TI  - Use of rabies virus as a transneuronal tracer of neuronal connections:
      implications for the understanding of rabies pathogenesis.
AB  - In neurosciences, rabies virus (CVS strain) has become a very powerful tool for
      studying multisynaptic neuronal connections, due to its ability to function as a
      self-replicating marker and to propagate exclusively between connected neurons by
      transneuronal transfer, which is strictly time-dependent. In this laboratory,
      transneuronal tracing studies of rabies virus propagation in primates and rodent
      models during the asymptomatic period have provided valuable information on
      rabies pathogenesis. We have shown that rabies virus propagates by fast axonal
      transport at similar speeds in primates and rodents, after inoculation into the
      peripheral or central nervous system (CNS). Intracellulartransport of rabies
      virus is preferentially addressed to neuronal dendrites rather than axons, since
      transneuronal transfer occurs only retrogradely, i.e., from dendrites of first
      infected neurons to presynaptic terminals of connected neurons. Rabies virus
      propagation occurs at chemical synapses, but not via gap junctions or local
      spread. The results of our studies show that rabies virus receptors have a
      ubiquitous distribution on neurons within the CNS. Conversely, in the peripheral
      nervous system, rabies virus receptors are present only on motor endings, since
      uptake is restricted to motor endplates and axons, whereas sensory and autonomic
      endings are not infected. Thus, after peripheral inoculations, motoneurons are
      the only gateway for rabies virus transmission to the CNS. Infection of sensory
      and autonomic neurons requires longer incubation times, since it reflects
      centrifugal propagation of rabies virus from the CNS to the periphery, i.e., it
      is the result of retrograde transneuronal transfer to sensory and autonomic
      terminals within the CNS.

PMID- 18634513
TI  - Rabies at the dawn of the twenty-first century.

PMID- 18634514
TI  - OIE guidelines on dog population control.
AB  - At the 73rd General Session the OIE decided to develop guidance for Members on
      humane methods for the control of stray animal populations. In 2006, an ad hoc
      Group was convened under the leadership of the OIE Permanent Animal Welfare
      Working Group. With valuable assistance from the OIE Collaborating Centre on
      Animal Welfare, a Questionnaire was developed and sent to OIE Members, of which
      81 countries submitted responses. In light of this information, the ad hoc Group
      prepared a first draft report, which notes the importance of controlling stray
      dog populations to help prevent zoonotic diseases and non-disease related
      nuisances to society and the environment. In choosing the preferred method of
      control, the risks to operators must be taken into account, as well as religious,
      cultural and economic contexts of the country concerned. Depending on the
      situation, methods requiring individual animal restraint or methods for use at a
      distance may be recommended. While activities that aim to physically reduce the
      numbers of stray dogs are important, achievement of the long term goals of dog
      population control and avoidance of risks to human health depends on the
      education of dog owners and the general public as to their responsibilities. The
      draft report notes that sub-national jurisdictions are often those responsible
      for the control of stray dog populations. The key role played by non-governmental
      organisations in stray dog management in many countries is acknowledged. The
      draft report emphasises that the close involvement of veterinarians and of
      official Veterinary Services, working in collaboration with public health
      authorities, is necessary to realise long term goals.

PMID- 18634515
TI  - What have we achieved since Kiev? Looking forward.
AB  - There have been many changes and accomplishments in rabies control and prevention
      since the first International conference "Rabies in Europe" was held in Kiev on
      June 15-18, 2005. Recommendations from the 2005 meeting addressed epidemiology;
      rabies diagnosis; animal rabies control; human rabies prevention; vaccinology and
      immunology and bat rabies. This paper will adhere to the same topics of interest
      in order to review the accomplishments that have been achieved since Kiev.

PMID- 18634516
TI  - Towards the elimination of rabies in Eurasia.

PMID- 18634517
TI  - Ten-day observation of live rabies suspected dogs.
AB  - This study aimed at analyzing a ten-day observation period of rabies suspected
      dogs and cats according to six criteria. Dogs and cats suspected of being rabid
      were brought for observation when they had either bitten a person or another
      animal or when abnormal behaviour or unusual illness was observed. Between 1985
      and 2005, retrospective and prospective data from 1,222 dogs and 303 cats was
      collected during the ten-day observation period. If an animal had died, brain
      examination using fluorescent antibody testing was routinely performed. If an
      animal had survived for > or =10 days, it was released to its owner or
      transferred to the municipal dog shelter. A total of 644 dogs and 58 cats found
      rabid died within 10 days of observation. In addition, for 208 dogs confirmed
      rabid with laboratory tests between 1997 and 2005, six criteria were analysed
      from the day of submission. This experience with the implemented 10-day
      observation period confirms the WHO recommendation on identifying suspected rabid
      dogs or cats under veterinary supervision following a human exposure.

PMID- 18634518
TI  - Active monitoring of EBLV infection in natural colonies of the mouse-eared Bat
      (Myotis myotis).
AB  - Bats are important reservoir hosts of RNA viruses, including lyssaviruses, which
      can cross the species barrier to infect humans and other domestic and wild non
      flying mammals. Six of the seven Lyssavirus genotypes described to date infect
      bats. In Europe, two genotypes of Lyssavirus, European bat Lyssavirus types 1 and
      2 (EBLV-1 and EBLV-2), circulate among several bat species and numerous bats are
      found infected every year. To provide epidemiologists and public health officials
      with data to effectively implement public health measures, we have undertaken
      field studies to identify the temporal dynamics of virus infection in bat
      colonies by combining multidisciplinary approaches. We have focused our work on a
      long-term longitudinal survey of different bat colonies in the Balearic Islands.
      The prevalence of virus RNA and neutralizing antibodies were analysed in captured
      bats. The bats were banded to allow for individual monitoring of infection and
      movements between colonies. The results show different lyssavirus infection
      episodes across the twelve years of study and provide the first evidence that
      mortality of the mouse-eared bat (Myotis myotis) in their natural environment
      does not increase significantly after episodes of EBLV-1 infection.

PMID- 18634519
TI  - WELYSSA: a simple tool using mouse monoclonal antibodies for the detection of
      lyssavirus nucleocapsid in rabies suspected specimens.
AB  - A Monoclonal antibody (MAb)-based capture enzyme-linked immunosorbent assay
      (ELISA) named WELYSSA was developed for the diagnosis of rabies suspected
      specimens using prototype viruses from the different genotypes of lyssavirus and
      from various geographic origins and phylogenetic lineages. It included a panel of
      1,660 specimens received for rabies diagnostic testing, and was found to be
      highly specific (99.9%) and sensitive (97.0%) when compared to other recommended
      rabies diagnostic methods.

PMID- 18634520
TI  - [Metabolic syndrome--the 21st century challenge].

PMID- 18634521
TI  - [Plasma urotensin II level in patients with chronic congestive heart failure].
AB  - Urotensin II (UTII) is recently discovered neurohumoral factor influencing
      function and structure of the myocardium and remodeling of the vessels, and it
      may contribute to pathogenesis of chronic congestive heart failure. The aim of
      the study was estimation of plasma concentration of UTII in patients with chronic
      congestive heart failure. The investigations were performed on 79 patients (37
      women and 42 men) aged 43-87 yr. (mean 69.2 +/- 9.8 yr.) and 15 healthy
      individuals. In all patients, echocardiographic examination of the left ventricle
      structure and function was performed and serum concentration of electrolytes and
      creatinine were measured. Plasma levels of UTII were determined before treatment
      and after 1 week, 2 and 4 weeks of treatment using RIA Peninsula Lab. Inc. Plasma
      level of UTII in patients suffering from chronic congestive heart failure was
      significantly lower than in healthy individuals before the treatment and after
      achieving compensation of the circulatory system using standard treatment,
      independently from sex, kind of heart failure (systolic-diastolic or diastolic)
      or coexistence arterial hypertension or pulmonary hypertension, ischemic heart
      disease or diabetes and impaired glucose tolerance. Treatment of chronic
      congestive heart failure resulted in a transient increase in UTII concentration
      except for patients with diastolic heart failure or diabetes. Only patients
      without ischemic heart disease have a permanent increase in UTII concentration at
      the time of the treatment. After achieving compensation of the circulatory system
      in the patients suffering from systolic-diastolic heart failure, UTII
      concentration was significantly lower than in the patients suffering from
      diastolic heart failure, in the patients suffering from ischemic heart disease
      significantly lower than in patients without ischemic heart disease, in the
      patients with arterial hypertension significantly higher than in those with
      normal arterial tension, in group of the patients with pulmonary hypertension
      lower than in group of the patients without pulmonary hypertension and
      significantly higher in group of the patients suffering from diabetes or impaired
      glucose tolerance than in group of the patients without this metabolic disorders.

PMID- 18634522
TI  - [Circadian profile of the prolactin concentration in the patients with end-stage
      renal failure].
AB  - Determination of circadian of prolactine (PRL) profile and its relationship to
      selected clinical and laboratory indices in end-stage renal disease (ESRD)
      patients undergoing hemodialysis, peritoneal dialysis as well as those in
      predialysis period was the aim of the study. Investigations were carried out in
      38 patients with ESRD aged 36 to 79 yr. (medium 59 +/- 11 yr.), (20 male, 18
      female, 7 treated with peritoneal dialysis, 25 undergoing hemodialysis, 6 in
      predialysis period) and the control group consisting of 7 healthy volunteers (4
      male and 3 female). Serum concentration of PRL was evaluated at 3:00, 7:00,
      12:00, 18:00, 22:00. The influence of different dialysis methods, blood
      concentration of parathormone, hemoglobin, total protein, erytropoietin (EPO), C
      reactive protein, EPO therapy and duration of dialysis therapy on the PRL profile
      was analyzed. Results were analyzed according to medium obtained values of daily
      PRL profiles and individual indexes of variation of the daily concentration.
      Impaired circadian PRL profile was found in the all of followed groups comparing
      to the control, which was based on flatting of the curve and decreasing of the
      nightly pick of secretion PRL. None of analyzed factors had normalized the PRL
      profile curve. CONCLUSIONS: The PRL profile in ESRD patients treated with
      hemodialysis, peritoneal dialysis and in predialysis period is changed. The PRL
      profile curve is flatted and there was no night pick of PRL secretion in the
      patients. PRL level was shown to increase with progress of the disease, and the
      highest levels were in hemodialysed patients. EPO treatment, general appearance
      improvement, increased hemoglobin level and any of studied different dialysis
      method did not normalize the altered PRL profile.

PMID- 18634523
TI  - [Metoclopramide test in the patients with hyperprolactinemia due to end-stage
      renal failure].
AB  - Evaluation of metoclopramide (MTC) test values in end-stage renal disease
      patients undergoing hemodialysis with different level of hyperprolactinemia was
      aim of the study. Clinical value of application of the MTC test and influence of
      different laboratory and clinical factors including erytropoietin treatment were
      examined. Sixty-eight hemodialysed patients (31 male and 37 female) aged 20-74
      yr. (medium 48 +/- 13 yr.) underwent the MTC test, the control group consisted of
      8 healthy volunteers (4 male and 4 female). 10mg of MTC was given i.v. and serum
      level of PRL was determined in 0, 30 and 60 min. after injection. Significant
      suppression of PRL stimulation in the patients was shown as compared with the
      controls after 30 min and delayed decrease of the curve values was found. An
      increase in the PRL level after 60 min in investigated group was lower than in
      control. Lower relative enhance of PRL level in 30 min was found and slower
      decrease after 60 min. Despite the slower decrease PRL level was lower in the
      patients than in the controls after 60 min. The highest relative increase in PRL
      level after 30 min was observed in the patients with lowest initial level of PRL
      (r=-0.471; p<0.001). Erytropoietin administration improved the response in the
      test (p=0.005) without relationship to the duration of erytropoietin treatment.
      There was influence of hemoglobin level on the results of the test. CONCLUSIONS:
      Results of the MTC test in end-stage renal disease patients is inadequate and the
      PRL response is diminished. Diagnostic value of the test in end-stage renal
      disease patients is low. Erytropoietin administration improves although not to
      the normal values the results of the MTC test.

PMID- 18634524
TI  - [Activity of cathepsin D in the blood serum and urine of patients with cancer of
      the stomach, pancreas and liver].
AB  - Cathepsin D is a protease involved in invasion of the cancer and metastasis
      formation. The purpose of the study was to evaluate a prognostic value of
      cathepsin D activity in blood serum and urine of patients with cancer of the
      stomach, pancreas and liver. The study was carried out on the samples of blood
      serum and urine obtained from patients with cancer of the stomach, pancreas and
      liver treated surgically at the First Department of General Surgery and
      Endocrinology of the Medical University of Bialystok. The control group consisted
      of healthy individuals. Activity of cathepsin D was determined in serum and urine
      by the Folin-Ciocaltau method with the cupric modification and was expressed in
      nmol Tyr/ml/6h. Specific activity of cathepsin D was determined in the urine, and
      was expressed in nmol Tyr/mg of protein/6h. Protein concentration in serum was
      assessed with Lowry et al. method and results were expressed in mg/ml. A
      significant increase in activity of cathepsin D in serum (p = 0.0169) and urine
      (p = 0.0008) and an enhanced specific activity in the urine (p = 0.0085) was
      found in patients with cancer of the pancreas as compared with the controls. A
      significantly increased activity of cathepsin was revealed in serum (p = 0.0233)
      of patients with cancer of the stomach. No significant differences of cathepsin D
      activity were found in urine of the patients with cancer of the stomach when
      compared to the controls. Additionally, an upward tendency (almost two-fold
      increase) of cathepsin D activity was shown in blood serum and an increase in the
      activity and in specific activity was observed in urine of both patients with
      cancer of the liver in comparison with the healthy individuals. There were no
      significant differences in the activity of cathepsin D in serum of the patients
      with cancer of the pancreas and stomach (p = 0.4156). A statistically
      significantly higher activity (p = 0.0004) and specific (0.0048) cathepsin D
      activity was demonstrated in urine of the patients with cancer of the pancreas in
      comparison with the patients with cancer of the stomach. Determination of protein
      level in urine proved a downward tendency in the patients with cancer of the
      stomach (p = 0.11109), as compared to the controls, and a statistically
      significant increase found in the patients with cancer of the pancreas (p =
      0.0238), in comparison with the patients with cancer of the stomach. In
      conclusion, investigation of cathepsin D activity in the blood serum of patients
      with cancer of the stomach and pancreas and in the urine of the patients with
      cancer of the pancreas may be usefull in clinical oncological diagnostics.
      However, further studies of the enzyme are necessary to establish the clinical
      value of cathepsin D measurement.

PMID- 18634525
TI  - [Application of the percutaneuos thrombin injection in treatment of iatrogenic
      femoral pseudoaneurysms].
AB  - Pseudoaneurysms are not a common complication of the endovascular procedures but
      can present a serious therapeutic problem. Both, the application of compression
      therapy and surgical operation can lead to the development of subsequent
      complications. The aim of this study was analysis of the treatment results of
      iatrogenic pseudoaneurysms managed with percutaneous thrombin injection. Treated
      group consisted of 69 patients diagnosed with iatrogenic femoral pseudoaneurysms.
      The indication for injection technique was ineffective compression therapy as
      well as necrotic changes or bacterial skin infection in the groin area or a large
      diameter of pseudoanurysm's chambers. Thrombin was injected percutaneously during
      1-3 sessions in the dose of 100-1200 U into the centre of the chamber under
      ultrasound control. Primary and secondary success rate was 88% and 94%
      respectively. The following factors significantly decreased effectiveness of the
      method: complex pseudoaneurysms (with treatment efficacy 82% and 88% respectively
      vs 90% and 96% for simple pseudoaneurysms), and large chamber volume. Early and
      late recanalization of the thrombotic changes appeared in 7% and 3% of treated
      cases. The most frequent complication was appearance of non-elastic tumor (71%)
      or pain (64%) in the groin area. The most serious complication was acute lower
      limb ischemia detected in one case (2%) as a result of femoral artery compression
      by the thrombosed pseudoaneurysm. Percutaneous thrombin injection should be a
      preferred method of pseudoaneurysms treatment, especially in cases of ineffective
      compression therapy or its contraindications due to low cost of the therapy,
      simplicity of the technique and relatively low percentage of the complications.

PMID- 18634526
TI  - [Changes of ventricular activation time in patients with left anterior fascicle
      block and bifascicular block].
AB  - Recognition of left anterior fascicle block is usually a diagnostic problem.
      Isochrone maps, displaying results of the body surface potential mapping are
      helpful in solving this problem. The isochrone maps present changes of heart
      electric field, especially those concerning a pathway of the depolarization front
      propagation within the heart conduction system. Body surface potential mapping
      registrations were performed using a Fukuda Denshi cylindrical system, which
      enables simultaneous recordings of electrocardiographic signals from the 87
      leads. The examined group consisted of 29 patients with left anterior fascicle
      block (LAFB) and complete right bundle branch block (RBBB) complicated by LAFB.
      The first group consisted of 7 females and 8 males with the mean age of 62 +/-
      11.3 yr., and the second group comprised 8 females and 6 males (the mean age: 64
      +/- 5.01 yr.). The control group comprised 30 healthy subjects--the mean age of
      50.3 +/- 5.63 yr. In all of examined patients, elementary biochemical tests,
      echocardiography and X-ray chest examinations were performed. In order to obtain
      a pattern reflecting a depolarization trajectory in the patients' heart, the
      ventricular activation time maps (VAT) were constructed, using the own software.
      This kind of maps is more precise than standard electrocardiograms and makes
      possible monitoring an activity propagation, as well as its velocity within the
      heart conduction system. In the patients demonstrating left anterior fascicle
      block, a subendocardial layer of the bottom left surface of the interventricular
      septum is the earliest stimulated area of heart (similarly, as in normal
      subjects). Afterwards, the front of stimulation wave crosses the septum from left
      to right side. In the next phase, the activation comprises right surface of the
      septum, as well as subendocardial surfaces of right ventricle free walls, however
      in the free wall of left ventricle, as a result of left anterior fascicle block,
      the activation spreads through back part of bundle branch. At this moment,
      isochrone lines arrange in bottom-right-forward direction. Subsequently, the
      delayed stimulation wave penetrates the anterior and lateral walls. Isochrones on
      the right torso are directed rightward and upward. In the final phase, the
      activation spreads over remaining part of the free wall of left ventricle, moving
      leftward, upward and backward. On isochrone maps, the final stage of activation
      propagation is seen on whole upper back part of the torso. In patients
      demonstrating RBBB with LAFB, the stimulation time is notably delayed. As a
      result of blocking the right ventricle and left anterior fascicle, the
      stimulation wave goes to the free wall of left ventricle through the back bundle.
      Isochrones distribution is similar like in left anterior fascicle block. However,
      different time of stimulation dispersal in downward direction is observed. Next,
      the wave propagation moves downward and leftward, coming to the anterior and
      lateral walls. Later on, a stimulation of the remaining part of the left
      ventricle free wall is observed, and isochrones wander to the heart bottom.
      Finally, after about 80 ms from the beginning, a delayed stimulation wave reaches
      the right ventricle, passing around the blocked area and spreading through
      terminal fibres within right ventricle. In the both examined groups no
      significant differences in relation to isochrones distribution were observed,
      therefore the averaged VAT maps were assumed as a reference pattern for the given
      groups. A pattern of VAT maps distribution and values of ventricular activation
      time can be useful in the further investigations concerning an analysis of wave
      propagation in bundle branch blocks.

PMID- 18634527
TI  - [SAPHO syndrome--clinical features].
AB  - OBJECTIVE: Presentation of clinical features of the SAPHO syndrome. MATERIALS AND
      METHODS: Seventeen patients (15 women and 2 men) with confirmed diagnosis of the
      SAPHO syndrome was presented. The culture of biopsy of pustulotic skin lesions
      was performed in 11 patients. ESR, C-reactive protein level and Waaler-Rose test
      were determined in all patients, and antinuclear antibodies and bone scintigraphy
      were performed in 16 patients. X-ray of the sterno-clavicular joints was
      performed in 15 patients. RESULTS: The age of patients was 22-59 yr. (mean: 47.1
      yr). The duration of joint symptoms was 0.1-25 yr. (mean: 4.4 years). Pustulosis
      was presented in 16 patients, only 1 patient had acne. All patients suffered from
      pain localized on the anterior chest wall. Tenderness of the peripheral joints:
      wrist (in 7 patients), shoulder (in 7 patients), knee (in 4 patients) was shown.
      In 6 patients, skin changes preceded joint symptoms, in 2 patients skin changes
      followed joint symptoms after 5 and 10 yr., respectively. All patients had
      negative the Waaler-Rose test. Active inflammatory process characterized by an
      increased ESR and C-reactive protein level was present in 12 patients.
      Abnormalities in x-ray of the sterno-clavicular joints were present in 4
      patients. Characteristic alternations for the SAPHO syndrome in scintigraphic
      picture of the skeleton were observed in 14 patients. All patients were treated
      with non-steroidal anti-inflammatory drugs. In 8 patients, treatment with
      antibiotics, in 11 patients--with sulfasalazine, in 3 patients--with methotrexate
      and low doses of glucocorticosteroids, in 1 patient--with colchicines was
      performed. CONCLUSIONS: Association of typical skin changes with pain of the
      anterior chest wall is the key for diagnosis of the SAPHO syndrome. It seems that
      this syndrome is more common in Poland than it has been previously estimated.

PMID- 18634528
TI  - [Hypopituitarism: interdisciplinary diagnostic issue].
AB  - A case of 68-aged male with hypopituitarism who suffered from faints and syncope
      with nauseas, vomiting and a significant body mass decrease, progressing during 3
      yr. was presented. Diagnosis of hypopituitarism was established 3 yr. after
      symptoms onset. Diagnostic problems concerning hypopituitarism were described,
      indicating consideration of this uncommon disease in differential diagnosis of
      disorders which major symptoms are faints and syncope.

PMID- 18634529
TI  - [Whipple's disease with generalized lymphadenopathy].
AB  - A case of Whipple's disease in 44 year-old man with generalized limphadenopathy
      of superficial and retroperitoneal lymph nodes was presented. Differential
      diagnostics with lymphatic neoplasm was necessary.

PMID- 18634530
TI  - [Polymorphic ventricular tachycardia of torsade de pointes type in patient with
      schizophrenia treated with thioridazine].
AB  - A case of 82 year-old female with schizophrenia treated with thioridazine with a
      long QT syndrome and polymorphic ventricular tachycardia of torsade de pointes
      type was presented. Additional predisposing factor for cardiac arrhythmia was
      diarrhea with subsequent hypokalemia. Infusion of magnesium sulphate, potassium
      supplementation and thioridazine discontinuation was effective management of the
      pathient.

PMID- 18634531
TI  - [The nail-patella syndrome: rare genetically determined cause of proteinuria].
AB  - Nail-patella syndrome (NPS) is rare genetic disorder with autosomal mode of
      inheritance resulting from mutations in the LMX1B gene mapped on the long arm of
      chromosome 9 (9q34), encoding transcription factor, also named LMX1B. This
      syndrome is characterized by a skeletal malformations, such as dysplasia of the
      knees (with typical patellar hypoplasia or aplasia), elbows and nails as well as
      characteristic protuberaces of ilium named ,,iliac homes". Chronic nephropathy
      and nails dysplasia are most common extraosseal signs of NPS. Familial, genetic
      proved (missense mutation -G599A (R200Q) case of NPS in the mother and her son
      was presented. Clinical features characteristic for this syndrome and observed in
      both our patients were compared to the data published previously.

PMID- 18634532
TI  - [Body mass reduction with over-the-counter medicines: myths and truth].

PMID- 18634533
TI  - [Cardiac sarcoidosis].

PMID- 18634535
TI  - [History of the Poznan Division of the Polish Society of Internal Medicine].

PMID- 18634534
TI  - [Inhaled insulin--the breakthrough in the treatment of diabetes?].

PMID- 18634536
TI  - Man is the way of medicine. The open letter of the President of the Polish
      Society of Internal Medicine issued on the hundredth anniversary of the Society
      foundation.

PMID- 18634537
TI  - Should you drink with your kids?

PMID- 18634539
TI  - To feed a hungry soul.

PMID- 18634538
TI  - Lessons in life (science).

PMID- 18634541
TI  - In high demand. Nurses spend most time away from bedsides: study.

PMID- 18634540
TI  - HHS shifts IT into high gear. New plan to promote information technology released
      to mostly good reviews, but concerns remain about its scope and funding.
AB  - HHS released an updated plan on promoting IT, and it won praise for its broad
      scope and organization. But there were criticisms--that it wasn't forceful enough
      in pushing for adoption and didn't do enough to marshal federal resources to meet
      goals. "The strong points are the emphasis on EHR adoption and interoperability
      ... on the other hand, the overall adoption goal was low," physician Andrew Ury,
      left, says.

PMID- 18634542
TI  - Not so fast. Joint Commission delays unpopular staff standard.

PMID- 18634543
TI  - Personal attention. Cecchettini recognized for improving patient-care processes
      at MultiCare.

PMID- 18634544
TI  - Making IT pervasive. Hawthorne has worked to immerse Texas Health Resources in
      technology.

PMID- 18634545
TI  - Reinforcing the 'backbone'. Partners' Mongan led charge to set deadline to get
      docs onboard for EMR.

PMID- 18634546
TI  - Stating their wishes. Healthcare IT initiatives gain in prominence among
      governors' priorities.

PMID- 18634547
TI  - How safe are vaccines?

PMID- 18634548
TI  - Battling brain cancer.

PMID- 18634549
TI  - Does physiotherapy reduce the incidence of postoperative complications in
      patients following pulmonary resection via thoracotomy? a protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Postoperative pulmonary and shoulder complications are important
      causes of postoperative morbidity following thoracotomy. While physiotherapy aims
      to prevent or minimise these complications, currently there are no randomised
      controlled trials to support or refute effectiveness of physiotherapy in this
      setting. METHODS/DESIGN: This single blind randomised controlled trial aims to
      recruit 184 patients following lung resection via open thoracotomy. All subjects
      will receive a preoperative physiotherapy information booklet and following
      surgery will be randomly allocated to a Treatment Group receiving postoperative
      physiotherapy or a Control Group receiving standard care nursing and medical
      interventions but no physiotherapy. The Treatment Group will receive a
      standardised daily physiotherapy programme to prevent respiratory and
      musculoskeletal complications. On discharge Treatment Group subjects will receive
      an exercise programme and exercise diary to complete. The primary outcome measure
      is the incidence of postoperative pulmonary complications, which will be
      determined on a daily basis whilst the patient is in hospital by a blinded
      assessor. Secondary outcome measures are the length of postoperative hospital
      stay, severity of pain, shoulder function as measured by the self-reported
      shoulder pain and disability index, and quality of life measured by the Medical
      Outcomes Study Short Form 36 v2 New Zealand standard version. Pain, shoulder
      function and quality of life will be measured at baseline, on discharge from
      hospital, one month and three months postoperatively. Additionally a subgroup of
      subjects will have measurement of shoulder range of movement and muscle strength
      by a blinded assessor. DISCUSSION: Results from this study will contribute to the
      increasing volume of evidence regarding the effectiveness of physiotherapy
      following major surgery and will guide physiotherapists in their interventions
      for patients following thoracotomy. TRIAL REGISTRATION: The study protocol is
      registered with the Australian and New Zealand Clinical Trials registry
      (ANZCTRN12605000201673).

PMID- 18634550
TI  - Low-molecular-weight heparins are superior to vitamin K antagonists for the long
      term treatment of venous thromboembolism in patients with cancer: a cochrane
      systematic review.
AB  - BACKGROUND: Cancer and its therapies increase the risk of venous thromboembolism.
      Compared to patients without cancer, patients with cancer anticoagulated for
      venous thromboembolism are more likely to develop recurrent thrombotic events and
      major bleeding. Addressing all important outcomes including harm is of great
      importance to make evidence based health care decisions. The objective of this
      study was to compare low molecular weight heparin (LMWH) and oral anticoagulants
      (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of
      venous thromboembolism in patients with cancer. METHODS: A systematic review of
      the medical literature. We followed the Cochrane Collaboration methodology for
      conducting systematic reviews. We assessed methodological quality for each
      outcome by grading the quality of evidence using the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Eight
      randomized controlled trials (RCTs) were eligible and reported data for patients
      with cancer. The quality of evidence was low for death and moderate for recurrent
      venous thromboembolism. LMWH, compared to VKA provided no statistically
      significant survival benefit (Hazard ratio (HR) = 0.96; 95% CI 0.81 to 1.14) but
      a statistically significant reduction in venous thromboembolism (HR = 0.47; 95%
      (Confidence Interval (CI) = 0.32 to 0.71). There was no statistically significant
      difference between LMWH and VKA in bleeding outcomes (RR = 0.91; 95% CI = 0.64 to
      1.31) or thrombocytopenia (RR = 1.02; 95% CI = 0.60 to 1.74). CONCLUSION: For the
      long term treatment of venous thromboembolism in patients with cancer, LMWH
      compared to VKA reduces venous thromboembolism but not death.

PMID- 18634551
TI  - Traditional zootherapeutic studies in India: a review.
AB  - The present study aims to review the zootherapeutic practices of the different
      ethnic communities of India. This work is also an attempt to present a list of
      animals' use for medicinal purposes by different communities of India. Data were
      gathered from 15 published research papers of various authors on zootherapeutic
      studies in India from 2000 to 2007. Approximately 109 animals and their 270 uses
      are reported in traditional medicine in different parts of India. Of these, the
      highest numbers of animal species (42, 38.5%) with 50 (18.5%) uses have been
      reported for the treatment of Respiratory system related problems. Rheumatic and
      other pains are treated with 32 species (29.4%) in 34 (12.9%) uses. Gastric
      problems are reported to be treated with 22 (20.2%) species in 26 (9.9%) uses.
      The mammals constitute the highest number of animals used for medicinal purposes.
      44 (40%) mammals, 24 (22%) invertebrates, 18 (17%) birds, 12 (11%) reptiles, nine
      (8%) fishes and two (2%) amphibians have been reported for medicinal purposes. Of
      the total 109 animal species reported, 76(70%) are included in IUCN red data list
      and 36 (33%) animal species are listed in CITES appendix I, II, and III. This
      work will be helpful in biodiversity conservation in India and also give a clue
      to investigate bio-active compound in these animal raw materials.

PMID- 18634552
TI  - Thai SF-36 health survey: tests of data quality, scaling assumptions, reliability
      and validity in healthy men and women.
AB  - BACKGROUND: Since its translation to Thai in 2000, the SF-36 Health Survey has
      been used extensively in many different clinical settings in Thailand. Its
      popularity has increased despite the absence of published evidence that the
      translated instrument satisfies scoring assumptions, the psychometric properties
      required for valid interpretation of the SF-36 summated ratings scales. The
      purpose of this paper was to examine these properties and to report on the
      reliability and validity of the Thai SF-36 in a non-clinical general population.
      METHODS: 1345 distance-education university students who live in all areas of
      Thailand completed a questionnaire comprising the Thai SF-36 (Version 1). Median
      age was 31 years. Psychometric tests recommended by the International Quality of
      Life Assessment Project were used. RESULTS: Data quality was satisfactory:
      questionnaire completion rate was high (97.5%) and missing data rates were low (<
      1.5% for all items). The ordering of item means within scales generally were
      clustered as hypothesized and scaling assumptions were satisfied. Known groups
      analysis showed good discriminant validity between subgroups of healthy persons
      with differing health states. However, some areas of concern were revealed.
      Possible translation problems of the Physical Functioning (PF) items were
      indicated by the comparatively low ceiling effects. High ceiling and floor
      effects were seen in both role functioning scales, possibly due to the
      dichotomous format of their response choices. The Social Functioning scale had a
      low reliability of 0.55, which may be due to cultural differences in the concept
      of social functioning. The Vitality scale correlated better with the Mental
      Health scale than with itself, possibly because a healthy mental state is central
      to the concept of vitality in Thailand. CONCLUSION: The summated ratings method
      can be used for scoring the Thai SF-36. The instrument was found to be reliable
      and valid for use in a general non-clinical population. Version 2 of the SF-36
      could improve ceiling and floor effects in the role functioning scales. Further
      work is warranted to refine items that measure the concepts of social
      functioning, vitality and mental health to improve the reliability and
      discriminant validity of these scales.

PMID- 18634553
TI  - Mycobacterium tuberculosis aortic graft infection with recurrent hemoptysis: a
      case report.
AB  - INTRODUCTION: Mycobacterium tuberculosis may cause a large variety of clinical
      presentations due to its ability to disseminate by contiguity or hematogenously.
      Tuberculosis may remain undiagnosed for years due to the chronic course of the
      disease, with potentially life-threatening long-term complications. CASE
      PRESENTATION: In this case report, we describe a tuberculous aortic graft
      infection in a 72-year-old man documented by polymerase chain reaction and
      cultures. The patient presented with three episodes of hemoptysis following a
      remote history of miliary tuberculosis. The infection was treated by graft
      replacement and prolonged antimycobacterial therapy. CONCLUSION: Tuberculous
      infection of a vascular graft is an uncommon complication, but should be
      considered in patients with an intravascular device and a history of previous
      tuberculosis, especially when hematogenous spread may have occurred a few months
      after surgery, or when an active mycobacterial infection is present in close
      proximity to the graft.

PMID- 18634555
TI  - Plenary lectures and symposia.

PMID- 18634554
TI  - Incorporation of enzyme concentrations into FBA and identification of optimal
      metabolic pathways.
AB  - BACKGROUND: In the present article, we propose a method for determining optimal
      metabolic pathways in terms of the level of concentration of the enzymes
      catalyzing various reactions in the entire metabolic network. The method, first
      of all, generates data on reaction fluxes in a pathway based on steady state
      condition. A set of constraints is formulated incorporating weighting
      coefficients corresponding to concentration of enzymes catalyzing reactions in
      the pathway. Finally, the rate of yield of the target metabolite, starting with a
      given substrate, is maximized in order to identify an optimal pathway through
      these weighting coefficients. RESULTS: The effectiveness of the present method is
      demonstrated on two synthetic systems existing in the literature, two pentose
      phosphate, two glycolytic pathways, core carbon metabolism and a large network of
      carotenoid biosynthesis pathway of various organisms belonging to different
      phylogeny. A comparative study with the existing extreme pathway analysis also
      forms a part of this investigation. Biological relevance and validation of the
      results are provided. Finally, the impact of the method on metabolic engineering
      is explained with a few examples. CONCLUSIONS: The method may be viewed as
      determining an optimal set of enzymes that is required to get an optimal
      metabolic pathway. Although it is a simple one, it has been able to identify a
      carotenoid biosynthesis pathway and the optimal pathway of core carbon metabolic
      network that is closer to some earlier investigations than that obtained by the
      extreme pathway analysis. Moreover, the present method has identified correctly
      optimal pathways for pentose phosphate and glycolytic pathways. It has been
      mentioned using some examples how the method can suitably be used in the context
      of metabolic engineering.

PMID- 18634557
TI  - Wednesday 5 september.

PMID- 18634556
TI  - Friday 7 september.

PMID- 18634558
TI  - Thursday 6 september.

PMID- 18634559
TI  - Acetylcholine inhibits cell cycle progression in rat Schwann cells by activation
      of the M2 receptor subtype.
AB  - Cultures of Schwann cells from neonatal rat sciatic nerves were treated with
      acetylcholine agonists and the effects on cell proliferation evaluated. (3)[H]
      thymidine incorporation shows that acetylcholine (ACh) receptor agonists inhibit
      cell proliferation, and FACS analysis demonstrates cell-cycle arrest and
      accumulation of cells in the G1 phase. The use of arecaidine, a selective agonist
      of muscarinic M2 receptors reveals that this effect depends mainly on M2 receptor
      activation. The arecaidine dependent-block in G1 is reversible because removal of
      arecaidine from the culture medium induces progression to the S phase. The block
      of the G1-S transition is also characterized by modulation of the expression of
      several cell-cycle markers. Moreover, treatment with ACh receptor agonist causes
      both a decrease in the PCNA protein levels in Schwann cell nuclei and an increase
      in p27 and p53 proteins. Finally, immuno-electron microscopy demonstrates that M2
      receptors are expressed by Schwann cells in vivo. These results indicate that
      ACh, by modulating Schwann cell proliferation through M2 receptor activation,
      might contribute to their progression to a more differentiated phenotype.

PMID- 18634560
TI  - Interaction between glutamate signalling and immune attack in damaging
      oligodendrocytes.
AB  - Glutamate is the principal excitatory neurotransmitter in the CNS, but it is also
      a potent neurotoxin that can kill nerve cells. Glutamate damages
      oligodendrocytes, like neurons, by excitotoxicity which is caused by sustained
      activation of AMPA, kainate and NMDA receptors. Glutamate excitotoxicity depends
      entirely on Ca(2+) overload of the cytoplasm and can be initiated by disruption
      of glutamate homeostasis. Thus, inhibition of glutamate uptake in isolated
      oligodendrocytes in vitro and in the optic nerve in vivo, is sufficient to
      trigger cell death which is prevented by glutamate receptor antagonists. In turn,
      activated, but not resting microglia, can compromise glutamate homeostasis and
      induce oligodendrocyte excitotoxicity, which is attenuated either by AMPA/kainate
      antagonists or by the blockade of the system x(c)- antiporter present in
      microglia. By contrast, non-lethal, brief, activation of glutamate receptors in
      oligodendrocytes rapidly sensitizes these cells to complement attack.
      Intriguingly, these effects are exclusively mediated by kainate receptors which
      induce Ca(2+) overload of the cytosol and the generation of reactive oxygen
      species. In conjunction, these observations reveal novel mechanisms by which
      neuroinflammation alters glutamate homeostasis and triggers oligodendrocyte
      death. Conversely, they also show how glutamate signaling in oligodendrocytes
      might induce immune attack. In both instances direct activation of glutamate
      receptors present in oligodendrocytes plays a pivotal role in either initiating
      or executing death signals, which might be relevant to the pathogenesis of white
      matter disorders.

PMID- 18634561
TI  - Potential role of the glial water channel aquaporin-4 in epilepsy.
AB  - Recent studies have implicated glial cells in novel physiological roles in the
      CNS, such as modulation of synaptic transmission, so it is possible that glial
      cells might have a functional role in the hyperexcitability that is
      characteristic of epilepsy. Indeed, alterations in distinct astrocyte membrane
      channels, receptors and transporters have all been associated with the epileptic
      state. This paper focuses on the potential roles of the glial water channel
      aquaporin-4 (AQP4) in modulating brain excitability and in epilepsy. We review
      studies of seizure phenotypes, K(+) homeostasis and extracellular space
      physiology of mice that lack AQP4 (AQP4(-/-) mice) and discuss the human studies
      demonstrating alterations of AQP4 in specimens of human epilepsy tissue. We
      conclude with new studies of AQP4 regulation by seizures and discuss its
      potential role in the development of epilepsy (epileptogenesis). Although many
      questions remain unanswered, the available data indicate that AQP4 and its
      molecular partners might represent important new therapeutic targets.

PMID- 18634562
TI  - Transcriptional regulation of PSA-NCAM mediated neuron-glial plasticity in the
      adult hypothalamus.
AB  - Gonadotropin releasing hormone (GnRH)-secreting neurons in mammal's project
      principally to the median eminence-arcuate (ME-ARC) region where they make
      contact with basal lamina and open into the pericapillary space of the primary
      hypophyseal portal plexus. In the present study we report the expression of
      polysialylated form of neural cell adhesion molecule (PSA-NCAM) on the cell
      bodies of GnRH-secreting neurons and on glial cells in the medial preoptic area
      (mPOA) of the hypothalamus in both the proestrous and diestrous phases of cycling
      rats, using dual immunohistofluorescent staining. Regulation of PSA-NCAM occurs
      via regulation of PSA biosynthesis by the polysialyltransferase enzyme (PST-1).
      Therefore, we studied the expression of PST mRNA and GnRH in GnRH-releasing cell
      bodies by combining fluorescent in situ hybridization with
      immunohistofluorescence, and expression of PST mRNA in the mPOA using northern
      blotting. We observed dynamic upregulation of PSA-NCAM on GnRH cell bodies in the
      proestrous phase, accompanied by enhanced expression of PST-1 mRNA. The present
      results indicate that PSA-NCAM has a permissive role in the structural remodeling
      of GnRH neurons. Enhanced expression of mRNA encoding PST-1 in the proestrous
      phase indicates that the biosynthesis of PSA and, thus, PSA-NCAM is regulated at
      the transcriptional level.

PMID- 18634563
TI  - Neuronal-glial interactions in central nervous system neurogenesis: the neural
      stem cell perspective.
AB  - Essentially, three neuroectodermal-derived cell types make up the complex
      architecture of the adult CNS: neurons, astrocytes and oligodendrocytes. These
      elements are endowed with remarkable morphological, molecular and functional
      heterogeneity that reaches its maximal expression during development when
      stem/progenitor cells undergo progressive changes that drive them to a fully
      differentiated state. During this period the transient expression of molecular
      markers hampers precise identification of cell categories, even in neuronal and
      glial domains. These issues of developmental biology are recapitulated partially
      during the neurogenic processes that persist in discrete regions of the adult
      brain. The recent hypothesis that adult neural stem cells (NSCs) show a glial
      identity and derive directly from radial glia raises questions concerning the
      neuronal-glial relationships during pre- and post-natal brain development. The
      fact that NSCs isolated in vitro differentiate mainly into astrocytes, whereas in
      vivo they produce mainly neurons highlights the importance of epigenetic signals
      in the neurogenic niches, where glial cells and neurons exert mutual influences.
      Unravelling the mechanisms that underlie NSC plasticity in vivo and in vitro is
      crucial to understanding adult neurogenesis and exploiting this physiological
      process for brain repair. In this review we address the issues of neuronal/glial
      cell identity and neuronal-glial interactions in the context of NSC biology and
      NSC-driven neurogenesis during development and adulthood in vivo, focusing mainly
      on the CNS. We also discuss the peculiarities of neuronal-glial relationships for
      NSCs and their progeny in the context of in vitro systems.

PMID- 18634564
TI  - Modulatory effects of oligodendrocytes on the conduction velocity of action
      potentials along axons in the alveus of the rat hippocampal CA1 region.
AB  - Like neurons and astrocytes, oligodendrocytes have a variety of neurotransmitter
      receptors and ion channels. However, except for facilitating the rapid conduction
      of action potentials by forming myelin and buffering extracellular K(+), little
      is known about the direct involvement of oligodendrocytes in neuronal activities.
      To investigate their physiological roles, we focused on oligodendrocytes in the
      alveus of the rat hippocampal CA1 region. These cells were found to respond to
      exogenously applied glutamate by depolarization through N-methyl-D-aspartate
      (NMDA) receptors and non-NMDA receptors. Electrical stimulation of the border
      between the alveus and stratum oriens evoked inward currents through several
      routes involving glutamate receptors and inward rectifier K(+) channels.
      Moreover, electrical stimulation resembling in vivo activity evoked long-lasting
      depolarization. To examine the modulatory effects of oligodendrocytes on neuronal
      activities, we performed dual, whole-cell recording on CA1 pyramidal neurons and
      oligodendrocytes. Direct depolarization of oligodendrocytes shortened the
      latencies of action potentials evoked by antidromic stimulation. These results
      indicate that oligodendrocytes increase the conduction velocity of action
      potentials by a mechanism additional to saltatory conduction, and that they have
      active roles in information processing in the brain.

PMID- 18634565
TI  - Reactive astrocytosis and glial glutamate transporter clustering are early
      changes in a spinocerebellar ataxia type 1 transgenic mouse model.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by an
      expanded CAG trinucleotide repeats within the coding sequence of the ataxin-1
      protein. In the present study, we used a conditional transgenic mouse model of
      SCA1 to investigate very early molecular and morphological changes related to the
      behavioral phenotype. In mice with neural deficits detected by rotarod
      performance, and simultaneous spatial impairments in exploratory activity and
      uncoordinated gait, we observed both significant altered expression and patchy
      distribution of excitatory amino acids transporter 1. The molecular changes
      observed in astroglial compartments correlate with changes in synapse morphology;
      synapses have a dramatic reduction of the synaptic area external to the
      postsynaptic density. By contrast, Purkinje cells demonstrate preserved
      structure. In addition, severe reactive astrocytosis matches changes in the glial
      glutamate transporter and synapse morphology. We propose these morpho-molecular
      changes are the cause of altered synaptic transmission, which, in turn,
      determines the onset of the neurological symptoms by altering the synaptic
      transmission in the cerebellar cortex of transgenic animals. This model might be
      suitable for testing drugs that target activated glial cells in order to reduce
      CNS inflammation.

PMID- 18634566
TI  - Adenosine dysfunction in astrogliosis: cause for seizure generation?
AB  - Epilepsy is characterized by both neuronal and astroglial dysfunction. The
      endogenous anticonvulsant adenosine, the level of which is largely controlled by
      astrocytes, might provide a crucial link between astrocyte and neuron dysfunction
      in epilepsy. Here we have studied astrogliosis, a hallmark of the epileptic
      brain, adenosine dysfunction and the emergence of spontaneous seizures in a
      comprehensive approach that includes a new mouse model of focal epileptogenesis,
      mutant mice with altered brain levels of adenosine, and mice lacking adenosine A1
      receptors. In wild-type mice, following a focal epileptogenesis-precipitating
      injury, astrogliosis, upregulation of the adenosine-removing astrocytic enzyme
      adenosine kinase (ADK), and spontaneous seizures coincide in a spatio-temporally
      restricted manner. Importantly, these spontaneous seizures are mimicked by
      untreated transgenic mice that either overexpress ADK in brain or lack A1
      receptors. Conversely, mice with reduced ADK in the forebrain do not develop
      either astrogliosis or spontaneous seizures. Our studies define ADK as a crucial
      upstream regulator of A1 receptor-mediated modulation of neuronal excitability,
      and support the ADK hypothesis of epileptogenesis in which upregulation of ADK
      during astrogliosis provides a crucial link between astrocyte and neuron
      dysfunction in epilepsy. These findings define ADK as rational target for
      therapeutic intervention.

PMID- 18634567
TI  - Adhesion molecules in the regulation of CNS myelination.
AB  - Myelination is necessary both for rapid salutatory conduction and the long-term
      survival of the axon. In the CNS the myelin sheath is formed by the
      oligodendrocytes. Each oligodendrocyte myelinates several axons and, as the
      number of wraps around each axon is determined precisely by the axon diameter,
      this requires a close, highly regulated interaction between the axons and each of
      the oligodendrocyte processes. Adhesion molecules are likely to play an important
      role in the bi-directional signalling between axon and oligodendrocyte that
      underlies this interaction. Here we review the current knowledge of the function
      of adhesion molecules in the different phases of oligodendrocyte differentiation
      and myelination, and discuss how the properties of these proteins defined by
      other cell biological systems indicates potential roles in oligodendrocytes. We
      show how the function of a number of different adhesion and cell-cell interaction
      molecules such as polysialic acid neural cell adhesion molecule, Lingo-1, Notch,
      neuregulin, integrins and extracellullar matrix proteins provide negative and
      positive signals that coordinate the formation of the myelin membrane. Compiling
      this information from a number of different cell biological and genetic
      experiments helps us to understand the pathology of multiple sclerosis and direct
      new areas of research that might eventually lead to potential drug targets to
      increase remyelination.

PMID- 18634569
TI  - Reflections on the conceptual origins of neuron--glia interactions.
AB  - Glial contributions to the functioning nervous system are now recognized widely.
      This was not always so. What follows is an account of the several mid-20th
      century events that led to the explicit proposition that glia and neurons
      collaborate in the production of behavioral responses.

PMID- 18634568
TI  - Interactions of Sox10 and Egr2 in myelin gene regulation.
AB  - Myelination in the PNS is accompanied by a large induction of the myelin protein
      zero (Mpz) gene to produce the most abundant component in peripheral myelin.
      Analyses of knockout mice have shown that the EGR2/Krox20 and SOX10 transcription
      factors are required for Mpz expression. Our recent work has shown that the
      dominant EGR2 mutations associated with human peripheral neuropathies cause
      disruption of EGR2/SOX10 synergy at specific sites, including a conserved
      enhancer element in the first intron of the Mpz gene. Further investigation of
      Egr2/Sox10 interactions reveals that activation of the Mpz intron element by Egr2
      requires both Sox10-binding sites. In addition, both Egr1 and Egr3 cooperate with
      Sox10 to activate this element, which indicates that this capacity is conserved
      among Egr family members. Finally, a conserved composite structure of Egr2/Sox10
      binding sites in the genes encoding Mpz, myelin-associated glycoprotein and
      myelin basic protein genes was used to screen for similar modules in other myelin
      genes, revealing a potential regulatory element in the periaxin gene. Overall,
      these results elucidate a working model for developmental regulation of Mpz
      expression, several facets of which extend to regulation of other peripheral
      myelin genes.

PMID- 18634570
TI  - Influence of adult Schwann cells and olfactory ensheathing glia on axon--target
      cell interactions in the CNS: a comparative analysis using a retinotectal co
      graft model.
AB  - We used an in vivo transplant approach to examine how adult Schwann cells and
      olfactory ensheathing glia OEG influence the specificity of axon-target cell
      interactions when they are introduced into the CNS. Populations of either Schwann
      cells or OEG were mixed with dissociated fetal tectal cells presumptive superior
      colliculus and, after reaggregation, pieces were grafted onto newborn rat
      superior colliculus. Both glial types were prelabeled with lentiviral vectors
      encoding green fluorescent protein. Grafts rapidly established fiber connections
      with the host and retinal projections into co-grafts were assessed 656 days
      posttransplantation by injecting cholera toxin B into host eyes. In control rats
      that received pure dissociated-reaggregated tectal grafts, retinal ganglion cell
      RGC axons selectively innervated defined target areas, corresponding to the
      retinorecipient layer in normal superior colliculus. The pattern of RGC axon
      ingrowth into OEG containing co-grafts was similar to that in control grafts.
      However, in Schwann cell co-grafts there was reduced host retinal input into
      presumptive target areas and many RGC axons were scattered throughout the
      neuropil. Given that OEG in co-grafts had minimal impact on axon-target cell
      recognition, OEG might be an appropriate cell type for direct transplantation
      into injured neuropil when attempting to stimulate specific pathway
      reconstruction.

PMID- 18634571
TI  - Gliosis alters expression and uptake of spinal glial amino acid transporters in a
      mouse neuropathic pain model.
AB  - Gliosis is strongly implicated in the development and maintenance of persistent
      pain states following chronic constriction injury of the sciatic nerve. Here we
      demonstrate that in the dorsal horn of the spinal cord, gliosis is accompanied by
      changes in glial amino acid transporters examined by immunoblot,
      immunohistochemistry and RT-PCR. Cytokines, proinflammatory mediators and
      microglia increase up to postoperative day (pd) 3 before decreasing on pd 7.
      Then, spinal glial fibrillary acidic protein increases on pd 7, lasting until pd
      14 and later. Simultaneously, the expression of glial amino acid transporters for
      glycine and glutamate (GlyT1 and GLT1) is reduced on pd 7 and pd 14. Consistent
      with a reduced expression of GlyT1 and GLT1, high performance liquid
      chromatography reveals a net increase in the concentration of glutamate and
      glycine on pd 7 and pd 14 in tissue from the lumbar spinal cord of neuropathic
      mice. In this study we have confirmed that microglial activation precedes
      astrogliosis. Such a glial cytoskeletal rearrangement correlates with a marked
      decrease in glycine and glutamate transporters, which might, in turn, be
      responsible for the increased concentration of these neurotransmitters in the
      spinal cord. We speculate that these phenomena might contribute, via over
      stimulation of NMDA receptors, to the changes in synaptic functioning that are
      responsible for the maintenance of persistent pain.

PMID- 18634573
TI  - A look inside.

PMID- 18634572
TI  - Cerebellar Bergmann glia: an important model to study neuron-glia interactions.
AB  - The biochemical effects triggered by the action of glutamate, the main excitatory
      amino acid, on a specialized type of glia cells, Bergmann glial cells of the
      cerebellum, are a model system with which to study glia-neuronal interactions.
      Neuron to Bergmann glia signaling is involved in early stages of development,
      mainly in cell migration and synaptogenesis. Later, in adulthood, these cells
      have an important role in the maintenance and proper function of the synapses
      that they surround. Major molecular targets of this cellular interplay are glial
      glutamate receptors and transporters, both of which sense synaptic activity.
      Glutamate receptors trigger a complex network of signaling cascades that involve
      Ca(2+) influx and lead to a differential gene-expression pattern. In contrast,
      Bergmann glia glutamate transporters participate in the removal of the
      neurotransmitter from the synaptic cleft and act also as signal transducers that
      regulate, in the short term, their own activity. These exciting findings
      strengthen the concept of active participation of glial cells in synaptic
      transmission and the involvement of neuron-glia circuits in the processing of
      brain information.

PMID- 18634574
TI  - Glial differentiation and the Gcm pathway.
AB  - One of the most challenging issues in developmental biology is to understand how
      cell diversity is generated. The Drosophila nervous system provides a model of
      choice for unraveling this process. First, many neural stem cells and lineages
      have been identified. Second, major molecular pathways involved in neural
      development and associated mutations have been characterized extensively in
      recent years. In this review, we focus on the cellular and molecular mechanisms
      underlying the generation of glia. This cell population relies on the expression
      of gcm fate determinant, which is necessary and sufficient to induce glial
      differentiation. We also discuss the recently identified role of gcm genes in
      Drosophila melanogaster and vertebrate neurogenesis. Finally, we will consider
      the Gcm pathway in the context of neural stem cell differentiation.

PMID- 18634575
TI  - Longitudinal glia in the fly CNS: pushing the envelope on glial diversity and
      neuron-glial interactions.
AB  - Interactions between neurons and glial cells are crucial for nervous system
      development and function in all complex organisms, and many functional,
      morphological and molecular features of glia are well conserved among species.
      Here we review studies of the longitudinal glia (LG) in the Drosophila CNS. The
      LG envelop the neuropil in a membrane sheath, and have features resembling both
      oligodendrocytes and astrocytes. Because of their unique lineage, morphology and
      molecular features, the LG provide an excellent model to study the genetic
      mechanisms underlying glial subtype differentiation and diversity, glial
      morphogenesis and neuron-glial interactions during development. In addition, they
      are proving useful in understanding how glial cells maintain ion and
      neurotransmitter homeostasis and protect neurons from environmental insult.

PMID- 18634576
TI  - Development of the peripheral glial cells in Drosophila.
AB  - In complex organisms the nervous system comprises two cell types: neurons and
      glial cells. Their correct interplay is of crucial importance during both the
      development of the nervous system and for later function of the nervous system.
      In recent years tools have been developed for Drosophila that enable genetic
      approaches to understanding glial development and differentiation. Focusing on
      peripheral glial cells we first summarize wild-type development, then introduce
      some of the relevant genes that have been identified. Despite obvious differences
      between Drosophila and mammalian glial cells, the molecular machinery that
      controls terminal differentiation appears well conserved.

PMID- 18634577
TI  - No pun intended: future directions in invertebrate glial cell migration studies.
AB  - Glial cells play a wide range of essential roles in both nervous system
      development and function and has been reviewed recently (Parker and Auld, 2006).
      Glia provide an insulating sheath, either form or direct the formation of the
      blood-brain barrier, contribute to ion and metabolite homeostasis and provide
      guidance cues. Glial function often depends on the ability of glial cells to
      migrate toward specific locations during nervous system development. Work in
      nervous system development in insects, in particular in the fruit fly Drosophila
      melanogaster and the tobacco hornworm Manduca sexta, has provided significant
      insight into the roles of glia, although the molecular mechanisms underlying
      glial cell migration are being determined only now. Indeed, many of the processes
      and mechanisms discovered in these simpler systems have direct parallels in the
      development of vertebrate nervous systems. In this review, we first examine the
      developmental contexts in which invertebrate glial cell migration has been
      observed, we next discuss the characterized molecules required for proper glial
      cell migration, and we finally discuss future goals to be addressed in the study
      of glial cell development.

PMID- 18634578
TI  - Ancestral roles of glia suggested by the nervous system of Caenorhabditis
      elegans.
AB  - The nematode Caenorhabditis elegans has a simple nervous system with glia
      restricted primarily to sensory organs. Some of the activities that would be
      provided by glia in the mammalian nervous system are either absent or provided by
      non-glial cell types in C. elegans, with only a select set of mammalian glial
      activities being similarly provided by specialized glial cells in this animal.
      These observations suggest that ancestral roles of glia may be to modulate
      neuronal morphology and neuronal sensitivity in sensory organs.

PMID- 18634579
TI  - Two distinct mechanisms segregate Prospero in the longitudinal glia underlying
      the timing of interactions with axons.
AB  - Prospero is required in dividing longitudinal glia (LG) during axon guidance;
      initially to enable glial division in response to neuronal contact, and
      subsequently to maintain glial precursors in a quiescent state with mitotic
      potential. Only Prospero-positive LG respond to neuronal ablation by over
      proliferating, mimicking a glial-repair response. Prospero is distributed
      unequally through the progeny cells of the longitudinal glioblast lineage. Just
      before axon contact the concentration of Prospero is higher in two of the four
      progeny cells, and after axon guidance Prospero is present only in six out of ten
      progeny LG. Here we ask how Prospero is distributed unequally in these two
      distinct phases. We show that before neuronal contact, longitudinal glioblasts
      undergo invaginating divisions, perpendicular to the ectodermal layer. Miranda is
      required to segregate Prospero asymmetrically up to the four glial-progeny stage.
      After neuronal contact, Prospero is present in only the LG that activate Notch
      signalling in response to Serrate provided by commissural axons, and Numb is
      restricted to the glia that do not contain Prospero. As a result of this dual
      regulation of Prospero deployment, glia are coupled to the formation and
      maintenance of axonal trajectories.

PMID- 18634580
TI  - Functional differentiation of human brain progenitor cells.
AB  - Stem cells and progenitor cells derived from the developing human brain have been
      shown to differentiate into neurons and astrocytes. However, few studies have
      examined the functional, physiological properties of these differentiated neurons
      and astrocytes. In this study we have used immunocytochemistry in combination
      with electrophysiology to examine protein machinery and functional properties of
      neurons and astrocytes differentiated from human brain progenitor cells
      (hBPCs).Our results show that serum induces mainly astrocytic phenotype cells
      that express GFAP and have physiological properties that are typical of
      astrocytes. hBPCs differentiated with BDNF and PDGF develop mainly into neurons
      expressing mature neuronal proteins MAP-2, synaptobrevin II and vesicular
      glutamate transporter I in the process, plus a small population of GFAP-positive
      radial cells. Based on electrophysiology of BDNF/PDGF-treated cells two classes
      of cell were identified. Class I cells have functional neuronal properties,
      including functional voltage-gated Na(+) and K(+) currents, functional AMPA
      receptors and the ability to generate action potentials. A smaller subpopulation
      of cells (Class II cells) expresses GFAP and exhibit functional properties of
      astrocytes, including linear current-voltage relationship and dye-coupling.

PMID- 18634581
TI  - Cryptic expression of functional glutamate transporters in the developing rodent
      brain.
AB  - The co-ordinate functioning of neurons and glia is required for glutamate
      mediated neurotransmission. In this study, we show by immunocytochemical
      detection of D-aspartate uptake, that functional glutamate transporters are
      present in the developing CNS of fetal and neonatal rats, including forebrain,
      midbrain and hindbrain, at least as early as embryonic day 12 (E12). Use of the
      transport inhibitor dihydrokainic acid revealed a significant role for GLT-1 in
      the uptake process.Immunolabelling for the glutamate transporters GLAST, GLT
      1alpha and GLT-1v showed that each of these proteins are expressed early in
      development and appear to be restricted to glial-like cells throughout the
      development period examined (except in the retina, where neuronal elements were
      also labelled). Our capacity to detect very early expression of the variant forms
      of GLT-1 contrasts with other studies, a feature that we attribute to the use of
      antigen-recovery techniques that unmask protein epitopes that are otherwise
      undetectable. These studies illustrate the widespread presence of functional
      glutamate transporters in the developing CNS, in many cases before the onset of
      periods of synaptogenesis and indicate that regulation of extracellular glutamate
      by multiple excitatory amino acid transporters might be crucial in early CNS
      development.

PMID- 18634582
TI  - Axonal signalling and the making of olfactory ensheathing cells: a hypothesis.
AB  - Olfactory ensheathing cells (OECs) are Schwann cell-like glial cells of the
      olfactory system that promote neural repair under experimental conditions. It is
      a matter of debate in how far OECs resemble Schwann cells and whether they
      possess specific properties. Although OECs have been characterized mainly with
      respect to their regenerative effects after transplantation, both their cellular
      identity and the regulating factors involved have remained vague. The aim of this
      article is to define OEC and Schwann-cell identity in molecular terms, and to
      discuss crucial factors that are involved in determination in vitro and in vivo.
      Distinct OEC features such as the down-regulation of the low affinity
      neurotrophin receptor p75(NTR) by neuronal contact are apparent in vivo under
      physiological conditions, whereas OECs acquire a Schwann cell-like phenotype and
      up-regulate p75(NTR) expression in vitro and following transplantation into the
      lesioned spinal cord. This might indicate that establishment of the OEC phenotype
      depends on specific axonal stimuli. In this review we hypothesize that OECs and
      Schwann cells possess malleable cellular phenotypes that acquire distinct
      features only upon specific interaction with their natural neuronal partner.This
      concept is consistent with previous findings in vitro and in vivo, and might be
      relevant for studies that use OECs and Schwann cells for nervous system repair.

PMID- 18634583
TI  - An animal model for late onset chronic demyelination disease caused by failed
      terminal differentiation of oligodendrocytes.
AB  - Various animal models are available for studying human multiple sclerosis (MS).
      Most of them model the initial phase of MS,including the immune-triggered attack
      of the myelin membrane and/or oligodendrocytes and, occasionally, demonstrate
      there mission and relapsing phases. However, few mimic the late chronic
      demyelinating phase. Overexpression of the proteolipid protein gene (Plp) causes
      a unique demyelinating disorder in mice in which normal-appearing myelin forms
      early in life and chronic demyelination occurs later. We found that remyelination
      is severely affected in this late demyelinating phase, but is not caused by
      deprivation of oligodendrocyte progenitors expressing PDGF receptor alpha
      (PDGFRa) and Olig2, which are present at an even higher number in the
      demyelinated white matter of the mutants than in wild-type controls. Furthermore,
      mature oligodendrocytes containing PLP were observed, but failed to remyelinate.
      The ability of oligodendrocytes from older transgenic animals to produce a myelin
      membrane-like structure was not impaired when cultured in vitro, which indicates
      that the lack of remyelination is not simply caused by changes in the intrinsic
      properties of the oligodendrocytes. Glial activation also occurred much earlier
      than active demyelination in mutant mice. Thus, in addition to intrinsic
      mechanisms, extrinsic mechanisms might also have an important role in defects of
      remyelination. These features are also observed in patients at a late stage of
      MS, leading to chronic demyelinating lesions. Thus, this mouse model partly
      mimics the late stage of MS and can be used to study the cause of inhibition of
      remyelination.

PMID- 18634584
TI  - Live imaging of glioblastoma cells in brain tissue shows requirement of actin
      bundles for migration.
AB  - Live-cell imaging of glioblastoma U373 and U87 cells transfected with actin
      cytoskeleton markers has been used to study there-arrangements that are
      associated with migration in two- and three-dimensional matrices and in brain
      tissue. In collagen gels and in brain slices, both cell types developed neuronal
      like processes with ruffling membranes and filopodia. Blebbing cells were also
      observed, but these were mainly immobile. The retraction of trailing cell
      processes in a tissue environment was associated with the transient development
      and contraction of bundles of axial stress fibers. The inhibition of Rho-kinase
      caused glioblastoma cells in brain slices to become immobile and develop neurite
      like processes at random, which indicates the requirement of Rho signaling and
      contractility for migration. Actin stress fibers were also observed in
      glioblastoma cells injected into the brains of living mice. Thus, invading
      glioblastoma cells use neurite-like extensions to penetrate between neuronal
      fibers and contractile actin bundles for traction of the cell body.

PMID- 18634585
TI  - Neurostatin: cellular sources and cellular targets of the inhibitor.
AB  - Neurostatin, a modified ganglioside in mammalian brain, is highly immunogenic.
      Fusion of spleen cells of Balb/C mice immunized with bovine neurostatin with
      SP(2)O myeloma cells, led to hybridoma producers of anti-neurostatin antibodies.
      Two,monoclonal, IgG secreters were selected that recognized the inhibitor in
      blots and tissue of cow, rat and pig. The lack of species specificity indicated
      that the molecular structure of the inhibitory epitope is similar in these
      mammals. That epitope was also present in other gangliosides of the b series,
      defining a new regulatory system of glial-cell proliferation and apoptosis. The
      antibodies further revealed the neuronal origin of neurostatin.

PMID- 18634586
TI  - Early events of peripheral nerve regeneration.
AB  - Early regeneration of injured peripheral nerves involves a series of events that
      are important in the success of eventual reconnection. In many nerve injuries,
      such as transections with gaps, axons and Schwann cells (SCs) penetrate into new
      microenvironments de novo, not involving zones of Wallerian degeneration. We
      studied unexplored axon-SC interactions by sampling of newly forming connections
      through a silicone conduit across transected rat sciatic peripheral nerve gaps.
      Axon and SC participation in bridge formation was addressed by light microscopy,
      electron microscopy and by double-labeling immunohistochemistry,including
      confocal imaging, and several, less appreciated aspects of early regrowth were
      identified. There are limitations to early and widespread regeneration of axons
      and SCs into bridges initially formed from connective tissue and blood
      vessels.Regrowth is 'staggered' such that only a small percentage of parent axons
      sampled the early bridge. There is an intimate, almost invariable relationship
      between SCs and extension of axons, which challenges the concept that axons lead
      and SCs follow.'Naked' axons were infrequent and limited in scope. Axons did not
      seek out and adhere to vascular laminin but intimately followed laminin deposits
      associated with apposed SCs. Growth cones identified by labeling of beta III
      tubulin, PGP(9 x 5) and GAP(43)/B(50) were complex, implying a pause in their
      regrowth, and were most prominent at the proximal stump-regenerative bridge
      interface. There is surprising and substantial hostility to local regrowth of
      axons into newly forming peripheral nerve bridges.Early axon outgrowth,
      associated with apposed Schwann cell processes, is highly constrained even when
      not exposed to adjacent myelin and products of Wallerian degeneration.

PMID- 18634587
TI  - Shapes of astrocyte networks in the juvenile brain.
AB  - The high level of intercellular communication mediated by gap junctions between
      astrocytes indicates that, besides individual astrocytic domains, a second level
      of organization might exist for these glial cells as they form communicating
      networks. Therefore,the contribution of astrocytes to brain function should also
      be considered to result from coordinated groups of cells. To evaluate the shape
      and extent of these networks we have studied the expression of connexin 43, a
      major gap junction protein in astrocytes, and the intercellular diffusion of gap
      junction tracers in two structures of the developing brain, the hippocampus and
      the cerebral cortex. We report that the shape of astrocytic networks depends on
      their location within neuronal compartments ina defined brain structure.
      Interestingly, not all astrocytes are coupled, which indicates that connections
      within these networks are restricted. As gap junctional communication in
      astrocytes is reported to contribute to several glial functions, differences in
      the shape of astrocytic networks might have consequences on neuronal activity and
      survival.

PMID- 18634588
TI  - New observations on the compact myelin proteome.
AB  - Myelin formation and maintenance depends on the establishment of two structurally
      and biochemically discernible domains: (a)compact myelin, that is multilamellar
      stacks of plasma membrane sheets; and (b) cytoplasmic channels that border the
      compact myelin domains, attach them to the cell body and anchor the myelin sheath
      to the axonal membrane. To identify proteins involved in the organization of
      these domains we took advantage of the high lipid content of compact myelin to
      separate it cleanly from other neural membranes and then used reverse-phase HPLC
      coupled to Electro-Spray Double Mass Spectrometry('MudPIT') to characterize the
      proteome of this sample. MudPIT allowed us to sidestep the bias of 2D-PAGE
      against either highly charged or transmembrane proteins. Thus, of 97 proteins
      that presented at least two, fully tryptic peptides (a stringent threshold),
      seven were well known myelin markers, including the mayor CNS myelin proteins:
      proteolipid protein and myelin basic protein, which are not resolvable by 2D
      PAGE. Furthermore, we have confirmed and extended the known compact myelin
      proteome by 22 proteins and confirmed that CNS and PNS myelinated tracts present
      Sirtuin 2, a tubulin deacetylase, and Septin7, a small GTPase that is likely to
      be involved in membrane and cytoplasm partitioning.

PMID- 18634589
TI  - Advances in understanding neuron-glia interactions.
AB  - Recent advances in the field of neuron-glia interactions were presented at the
      27th International Symposium of the University of Montreal Center de Recherche en
      Sciences Neruologiques. Topics included synaptogenesis, regulation of synaptic
      strength by glia at the neuromuscular junction and hippocampus; myelin formation,
      structure, and maintenance; involvement of glia in nervous-system response to
      injury, hypoxia, and ischemia; neurogenesis and apoptosis, and microglial
      involvement in chronic pain.

PMID- 18634590
TI  - Neuron-glia interactions in the hypothalamus.
AB  - The supraoptic (SON) and paraventricular (PVN) magnocellular nuclei of the
      hypothalamus undergo reversible anatomical remodeling under conditions of intense
      secretion of neurohypophysial hormones, such as lactation and chronic
      dehydration. This morphological plasticity is characterized by a pronounced
      reduction in astrocytic coverage of neurons, which results in an increased number
      and extent of directly juxtaposed somatic and dendritic surfaces. As a
      consequence, astrocyte-mediated clearance of glutamate from the extracellular
      space is altered, which causes an increased concentration and range of action of
      the excitatory amino acid in the extracellular space. This leads to a reduction
      of synaptic efficacy at excitatory and inhibitory inputs through the activation
      of presynaptic metabotropic glutamate receptors. By contrast, the action of glio
      transmitters released from astrocytes and acting on adjacent magnocellular
      neurons is limited during such anatomical remodeling. This includes glia derived
      ATP mediating potentiation of glutamatergic transmission, a process compromised
      by the neuronal-glial reorganization.Together, these studies on hypothalamic
      magnocellular nuclei provide new insights on the contribution of glial cells on
      neuronal activity.

PMID- 18634591
TI  - Reshaping neuron-glial communication at hippocampal synapses.
AB  - Neuron-glial interactions in the nervous system are of fundamental importance to
      many processes including neural migration,axon guidance, myelination and synaptic
      transmission. At synapses in the CNS, the physiological and structural
      relationship between neurons and astrocytes is particularly complex. The
      juxtaposition of astrocytic membranes with presynaptic and postsynaptic elements
      is important for regulating synaptic transmission and plasticity. Recent
      investigations demonstrate that the morphology of both neuronal and glial
      components show rapid, continuous structural remodeling in the hippocampus.These
      physical modifications are likely to have a significant functional impact upon
      neurotransmission and indicate that there modeling of astrocytic morphology might
      be crucial for the dynamic regulation of the synapse and its microenvironment. In
      this review, we focus on the structural complexities of astrocyte-synapse
      interactions in the hippocampus and their implications for understanding synaptic
      physiology, behavior and disease.

PMID- 18634592
TI  - Effects of glutathione depletion on the viability of human NT2-derived neuronal
      and astroglial cultures.
AB  - The level of glutathione (GSH) is often reduced in brains that are affected by
      neurodegeneration. It is not known, however,whether this is a cause or a
      consequence of the disease. Here we have examined the effects of GSH depletion on
      the viability of human neurons cultured in either the presence or the absence of
      astrocytes, both derived from NT2/D1 cells. We established that the endogenous
      concentration of GSH is 10 times lower in neurons than in astrocytes (1.42 versus
      18.9 pmol microg protein(-1)) and that pure neuronal cultures begin to die by
      apoptosis within 24 h of GSH depletion. By contrast, neurons that are co-cultured
      with astrocytes remain viable for several days, even with a profoundly decreased
      GSH content. However, they die rapidly when challenged additionally with
      nitrative stress. In addition, astrocytes survive for prolonged periods of time
      (>12 days) under severely reduced GSH concentrations. Our study shows clear
      differences in the content and sensitivity to depletion of GSH in neurons and
      astrocytes and establishes the significance of neuronal-glial interactions for
      the maintenance of neuronal viability under reduced GSH content. However, with
      chronic GSH depletion, these interactions might not be sufficient to protect
      neurons from other injurious factors (i.e. reactive oxygen and nitrogen species),
      which indicates that defective GSH metabolism might facilitate the progression of
      neurodegeneration.

PMID- 18634593
TI  - Estrogen and hippocampal synaptic plasticity.
AB  - During the past several years, there has been increasing interest in the effects
      of estrogen on neural function. This enthusiasm is driven, in part, by the
      results of early clinical studies suggesting that estrogen therapy given after
      menopause may prevent, or at least delay, the onset of Alzheimer's disease in
      older women. However, later clinical trials of women with probable Alzheimer's
      disease had contrary results. Much of the current research related to estrogen
      and brain function is focused in two directions. One involves clinical studies
      that examine the potential of estrogen in protecting against cognitive decline
      during normal aging and against Alzheimer's disease (neuroprotection). The other
      direction, which is the primary focus of this review, involves laboratory studies
      that examine the mechanisms by which estrogen can modify the structure of nerve
      cells and alter the way neurons communicate with other cells in the brain
      (neuroplasticity). In this review, we examine recent evidence from experimental
      and clinical research on the rapid effects of estrogen on several mechanisms that
      involve synaptic plasticity in the nervous system,including hippocampal
      excitability, long-term potentiation and depression related to sex and aging
      differences, cellular neuroprotection and probable molecular mechanisms of the
      action of estrogen in brain tissue.

PMID- 18634594
TI  - Regulation of neurogenesis by neurotrophins: implications in hippocampus
      dependent memory.
AB  - Neurogenesis, the generation of new neurons from neural precursor cells (NPCs),
      is a multi-step process that includes the proliferation of NPCs, fate
      determination, migration, and neuronal maturation. Neurogenesis is regulated by
      several extrinsic factors,such as enriched environment, physical exercise,
      hormones and stress, many of which also induce the expression of neurotrophins.In
      this review, we summarize studies on the role of neurotrophins in neurogenesis
      during development and in adults.We discuss the functional significance of
      neurogenesis in learning and memory, and how neurotrophins regulate this
      process.In this context, we describe recent experiments linking adult
      neurogenesis to long-term synaptic plasticity in the hippocampal dentate gyrus.
      Further study of the relationship between neurotrophins, adult neurogenesis and
      dentate synaptic plasticity might provide new insights into the mechanisms by
      which gene-environment interactions control cognition and brain plasticity.

PMID- 18634595
TI  - A focal adhesion-like process underlies induction of long-term potentiation in
      the Schaffer collateral-CA1 region of the hippocampus.
AB  - In the series of experiments reported here we provide evidence that a focal
      adhesion-like process underlies the induction of long-term potentiation (LTP) in
      the Schaffer Collateral-CA1 projection in the hippocampus. Here we show that an
      integrin binding peptide (RGD) impairs induction of Schaffer Collateral-CA1 LTP
      in hippocampal slice preparations in vitro. The heparin-binding peptide that
      binds heparan sulfate proteoglycan (HSPG) and blocks the formation of focal
      adhesions also impairs induction of LTP. Either the integrin-binding peptide or
      heparin-binding peptide reduces LTP partially. However, when the two peptides
      were administered simultaneously, there was no LTP 1 hour after induction. This
      indicates that these two molecules might function together and that a focal
      adhesion-like process might be involved in the induction of LTP. Additionally,we
      report that the RGD effect on LTP is time dependent and occurs only in the first
      few minutes following LTP induction, that the binding of the RGD peptide in CA1
      stratum radiatum increases after LTP induction and that this increased binding
      depends on Ca(2+). Using electron microscopy we show that integrins are present
      in synapses.

PMID- 18634596
TI  - Oligodendrocytes assist in the maintenance of sodium channel clusters independent
      of the myelin sheath.
AB  - To ensure rapid and efficient impulse conduction, myelinated axons establish and
      maintain specific protein domains. For instance, sodium (Na+) channels accumulate
      in the node of Ranvier; potassium (K+) channels aggregate in the juxtaparanode
      and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the
      mechanisms that control the initial clustering of these proteins is limited and
      less is known about domain maintenance. Correlative data indicate that myelin
      formation and/or mature myelin-forming cells mediate formation of all three
      domains. Here, we test whether myelin is required for maintaining Na+ channel
      domains in the nodal gap by employing two demyelinating murine models: (1)
      cuprizone ingestion, which induces complete demyelination through oligodendrocyte
      toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo
      spontaneous adult-onset demyelination without oligodendrocyte death. Our data
      indicate that the myelin sheath is essential for long-term maintenance of sodium
      channel domains; however, oligodendrocytes, independent of myelin, provide a
      partial protective influence on the maintenance of nodal Na+ channel clusters.
      Thus, we propose that multiple mechanisms regulate the maintenance of nodal
      protein organization. Finally, we present evidence that following the loss of Na+
      channel clusters the chronological progression of expression and reclustering of
      Na+ channel isoforms during the course of CNS remyelination recapitulates
      development.

PMID- 18634597
TI  - Transplanted olfactory ensheathing cells modulate the inflammatory response in
      the injured spinal cord.
AB  - Transplantation of olfactory ensheathing cells (OECs) into the injured spinal
      cord has been shown to exert neuroprotective effects and promote functional
      recovery. In the present study, we investigated the potential modulatory effects
      of OECs on the inflammatory reaction developed after photochemical injury to the
      spinal cord. OEC cultures were obtained from olfactory bulbs of adult Sprague
      Dawley rats. Photochemical spinal cord injury was induced in adult rats at T8.
      Thirty minutes after the insult, either a suspension of OECs (180 000 cells in 12
      microl DMEM) or DMEM alone was injected into the lesioned spinal cord.At 3, 7 and
      14 days post-operation (dpo), five animals from each group were processed for
      histology. Double-fluorescent labeling of transverse sections of the cord were
      made by combination of immunohistochemistry for inflammatory markers, interleukin
      1b(IL-1b) and inducible nitric oxide synthase (iNOS), and for selective markers
      of astrocytes (glial fibrillar acidic protein; GFAP)and microglia/macrophages
      (tomato lectin; LEC). Differences in the intensity and time course of glial
      response, and IL-1band iNOS expression were found between the two groups of rats.
      The reactivity grade against IL-1beta, iNOS, GFAP and LEC in OEC-transplanted
      rats was higher at 7 dpo and lower at 14 dpo compared with DMEM-injected rats.
      These results indicate that the mechanisms underlying neuroprotection by OECs
      might be caused by earlier, higher and shorter duration of microglia/macrophage
      and astrocyte responses after injury.

PMID- 18634598
TI  - Memory beyond the synapse.
AB  - Based on studies of the molecular and cellular cascades that occur during memory
      consolidation for a one-trial passive-avoidance learning task in the young chick,
      I review the evidence that memory is encoded in permanent changes in synaptic
      connectivity ina specific brain region, the Hebb hypothesis. I conclude that
      despite the fact that such a cascade occurs, culminating in the synthesis of cell
      adhesion molecules that are involved in synaptic remodelling, synaptic events are
      not in themselves sufficient to account for the phenomena of memory. Both whole
      brain (neuromodulator) and whole body (hormonal) processes are engaged.Memories
      are labile, disarticulated and stored in a distributed manner; how the mind/brain
      recreates coherent memories from this pattern is a mystery.

PMID- 18634599
TI  - Steroid-induced hippocampal synaptic plasticity: sex differences and
      similarities.
AB  - Early in development, steroid hormones structurally organize various regions of
      the CNS. However, steroid hormones continue to affect the structure and function
      of the CNS throughout the life of the individual. In this review, we discuss sex
      differences and similarities in steroid-induced synaptic plasticity in the adult
      brain. Particular emphasis is placed on steroid-induced plasticity in the
      hippocampus, a brain region important in learning and memory. This topic is
      relevant to the growing evidence for the actions of sex hormones outside of the
      reproductive neuroendocrine axis. It also tells an important and emerging story
      about non-genomic and genomic actions of steroids at the cellular and molecular
      levels. Specifically, the effects of estrogen and progesterone as well as the
      androgens and glucocorticoids are discussed. The influence of steroids on
      hippocampal structure and function can differ vastly between the sexes. However,
      there are certain similarities that might aid in our understanding of how
      steroids affect CNS plasticity in general. Although future studies will
      undoubtedly lead us to a greater understanding of these phenomena, the data
      reviewed indicate that when studying synaptic plasticity, the sex and hormonal
      milieu of the individual might significantly influence the outcome and
      interpretation of the research.

PMID- 18634601
TI  - Emotional and cognitive reinforcement of rat hippocampal long-term potentiation
      by different learning paradigms.
AB  - In earlier studies we have shown that a protein-synthesis-independent, early,
      long-term potentiaton (early-LTP) that lasts up to 4-5 hours can be transformed
      (reinforced) into a protein-synthesis-dependent late-LTP that lasts > or = 8
      hours by either an emotional challenge (e.g. swim stress) or mastering a
      cognitive task (e.g. spatial learning). In the present study we show that LTP
      reinforcement by spatial training depends on the specific constraints of the
      learning paradigm. In a holeboard paradigm,LTP-reinforcement is related to the
      formation of a lasting reference memory whereas water-maze training gives more
      heterogenous results. Thus, cognitive aspects interfere with emotionally
      challenging components of the latter paradigm. These data indicate that different
      spatial-learning tasks are weighted distinctly by the animal. Thus, we show that
      aspects of specific spatial learning paradigms such as shifts of attention and
      emotional content directly influence functional plasticity and memory formation.

PMID- 18634602
TI  - Contribution of Muller cells toward the regulation of photoreceptor outer segment
      assembly.
AB  - The assembly of photoreceptor outer segments into stacked discs is a complicated
      process, the precise regulation of which remains a mystery. It is known that the
      integrity of the outer segment is heavily dependent upon surrounding cell types
      including the retinal pigment epithelium and Muller cells; however the role
      played by Muller cells within this photoreceptor-specific process has not been
      fully explored. Using an RPE-deprived but otherwise intact Xenopus laevis eye
      rudiment preparation, we reveal that Muller cell involvement in outer segment
      assembly is dependent upon the stimulus provided to the retina. Pigment
      epithelium-derived factor is able to support proper membrane folding after
      inhibition of Muller cell metabolism by alpha-aminoadipic acid, while isopropyl
      beta-D-thiogalactoside, a permissive glycan, requires intact Muller cell
      function. These results demonstrate that both intrinsic and extrinsic redundant
      mechanisms exist to support the ability of photoreceptors to properly assemble
      their outer segments. Our study further suggests that the receptor for pigment
      epithelium-derived factor resides in photoreceptors themselves while that for
      permissive glycans is likely localized to Muller cells, which in turn communicate
      with photoreceptors to promote proper membrane assembly.

PMID- 18634603
TI  - Minocycline attenuates nitric oxide-mediated neuronal and axonal destruction in
      vitro.
AB  - Minocycline, a tetracycline derivative with pleiotropic biological effects,
      exhibits anti-inflammatory properties in several models of CNS disease. In
      addition to reducing production of inflammatory mediators, it has been postulated
      that minocycline might also be directly neuroprotective under these
      circumstances. Therefore, we investigated the effect of minocycline on primary
      cortical neuronal cultures exposed to a nitric oxide (NO)-donor. Cultures were
      assessed for neuronal survival, axon survival and markers of intracellular
      signaling pathways. The NO donor significantly increased neuronal death and
      minocycline was protective under these conditions. Furthermore NO-induced
      reductions in axonal length were significantly attenuated by
      minocycline.Improvements in axonal length were dependent on mitogen-activated
      protein kinase (MAP kinase)/extracellular signal-related kinase (Erk) signaling,
      whereas phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling was important
      in neuronal survival.Further investigation into MAP kinase signaling pathways
      revealed inhibition of p38 MAP kinase and c-jun N-terminal kinase(JNK) signaling
      by minocycline. JNK pathways were activated by trophic factor-withdrawal and
      minocycline attenuated neuronal death induced by trophic withdrawal. These
      results indicate that, in addition to anti-inflammatory properties, minocycline
      has direct protective effects on neurons and provides further evidence for its
      use in disorders of the CNS.

PMID- 18634600
TI  - Bipolar disorder: involvement of signaling cascades and AMPA receptor trafficking
      at synapses.
AB  - There is increasing evidence that severe mood disorders are associated with
      impairment of structural plasticity and cellular resilience. Cumulative data
      demonstrate that mood stabilizers regulate intracellular signaling cascades,
      including protein kinase C (PKC), PKA, mitogen-activated protein (MAP) kinase,
      glycogen synthase kinase 3-beta (GSK3-beta) and intracellular calcium, which are
      signaling pathways that regulate synaptic plasticity. In this context, it is
      noteworthy that a growing body of data indicates that the glutamatergic system,
      has a major role in neuronal plasticity and cellular resilience, might be
      involved in the pathophysiology and treatment of mood disorders. AMPA glutamate
      receptor trafficking is important in synaptic plasticity and might play crucial
      roles in maintaining critical neuronal circuits associated with mood. Two
      clinically effective, structurally dissimilar, antimanic agents, lithium and
      valproate (VPA), down-regulate synaptic expression of AMPA receptor subunit GluR1
      in hippocampus in chronically treated rats. This reduction in synaptic GluR1 by
      lithium and VPA is due to attenuated phosphorylation of GluR1 at a specific PKA
      site (residue 845 of GluR1), which is crucial for AMPA receptor insertion. By
      contrast,imipramine, which can provoke mania, increases synaptic expression of
      GluR1 in the hippocampus in vivo. Furthermore, there is ample evidence from
      preclinical and clinical research that the glutamatergic system is involved in
      the pathophysiology of mood disorders and that many of the somatic treatments
      used for mood disorders including antidepressants, mood stabilizers, atypical
      antipsychotic drugs and electroconvulsive therapy have both direct and indirect
      effects on the glutamatergic system. Given these findings, further research with
      medications that specifically affect the glutamatergic system is warranted.
      Recent studies in our lab have shown that riluzole, a FDA approved medicine that
      regulates the glutamatergic system, shows antidepressant efficacy in unipolar and
      bipolar depression. These studies indicate that regulation of glutamate-mediated
      synaptic plasticity might play a role in the treatment of mood disorders, and
      raise new avenues for novel therapies for this devastating illness.

PMID- 18634605
TI  - Prostaglandin E(2) metabolism is activated in Schwann cell lines derived from
      human NF1 malignant peripheral nerve sheath tumors.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are characteristic of
      Neurofibromatosis type 1 (NF1), a human genetic disorder affecting approximately
      1 in 3000 individuals. The absence of neurofibromin in Schwann cells results in
      hyperactivation of Ras, which contributes to Schwann cell hyperplasia. However,
      additional intracellular abnormalities in Schwann cells might contribute to the
      malignancy. We now report that cell lines derived from MPNSTs secrete elevated
      levels of prostaglandin E(2) (PGE(2)), express higher levels of phosphorylated
      mitogen-activated protein kinase (MAPK), phosphorylated cytosolic
      phospholipaseA(2) (cPLA(2)) and cyclooxygenase 2 (COX-2) when compared to normal
      adult human Schwann cells (nhSCs). PCR analysis reveals that NF1 MPNST cell lines
      express mRNA for both EP2 and EP4 prostaglandin E2 receptors, whereas nhSCs
      express only the EP4 receptor. COX-2 inhibitors and PGE(2) receptor antagonists
      decrease the proliferation of MPNST cell lines. These results indicate that
      prostaglandin metabolism is activated in MPNSTs and might contribute to tumor
      growth in NF1.

PMID- 18634606
TI  - Editorial.

PMID- 18634607
TI  - Axonal cell-adhesion molecule L1 in CNS myelination.
AB  - Of the axonal signals influencing myelination, adhesion molecules expressed at
      the axonal surface are strong candidates to mediate interactions between
      myelinating cells and axons. The recognition cell-adhesion molecule L1, a member
      of the immunoglobulin superfamily has been shown to play important roles in
      neuronal migration and survival, and in PNS myelination. We have investigated the
      role of axonally expressed L1 in CNS myelination. In co-cultures of myelinating
      oligodendrocytes and neurons derived from murine brain, we demonstrate that,
      before myelination, L1 immunoreactivity is confined to neurites. After
      myelination commences, L1 expression is downregulated on myelinated axons and
      adjacent, but not yet myelinated, internodes.Interfering with L1 before the onset
      of myelination, by adding either anti-L1 antibody or L1-Fc fusion proteins to the
      culture medium, inhibits myelination. In addition, in purified cultures of
      oligodendrocytes, L1-Fc fusion protein prevents lysophosphatidic acid-induced
      activation of the mitogen-activated kinase (MAP)-kinase pathway. Together, our
      data indicate that L1 is involved in the initiation of CNS myelination, and that
      this effect might involve the dephosphorylation of oligodendroglial
      phosphoproteins.

PMID- 18634608
TI  - Control of axonophilic migration of oligodendrocyte precursor cells by Eph-ephrin
      interaction.
AB  - The migration of oligodendrocyte precursor cells (OPCs) is modulated by secreted
      molecules in their environment and by cell-cell and matrix-cell interactions.
      Here, we ask whether membrane-anchored guidance cues, such as the ephrin ligands
      and their Eph receptors, participate in the control of OPC migration in the optic
      nerve. We postulate that EphA and EphB receptors, which are expressed on axons of
      retinal ganglion cells, interact with ephrins on the surface of OPCs. We show the
      expression of ephrinA5, ephrinB2 and ephrinB3 in the migrating OPCs of the optic
      nerve as well as in the diencephalic sites from where they originate. In
      addition, we demonstrate that coated EphB2-Fc receptors, which are specific for
      ephrinB2/B3 ligands, induce dramatic changes in the contact and migratory
      properties of OPCs, indicating that axonal EphB receptors activate ephrinB
      signaling in OPCs.Based on these findings, we propose that OPCs are characterized
      by an ephrin code, and that Eph-ephrin interactions between axons and OPCs
      control the distribution of OPCs in the optic axonal tracts, and the progress and
      arrest of their migration.

PMID- 18634609
TI  - Satellite cells of dorsal root ganglia are multipotential glial precursors.
AB  - The evolutionary origin of myelinating cells in the vertebrate nervous system
      remains a mystery. A clear delineation of the developmental potentialities of
      neuronal support cells in the CNS and PNS might aid in formulating a hypothesis
      about the origins of myelinating cells. Although a glial-precursor cell in the
      CNS can differentiate into oligodendrocytes (OLs), Schwann cells (SCs) and
      astrocytes, a homologous multipotential cell has not yet been found in the PNS.
      Here, we identify a cell type of embryonic dorsal root ganglia (DRG) of the PNS -
      the satellite cell - that develops into OLs, SCs and astrocytes.
      Interestingly,satellite-cell-derived OL precursors were found in cultures
      prepared from embryonic day 17 (E17) to postnatal day 8 (P8) ganglia,but not from
      adult DRGs, revealing a narrow developmental window for multipotentiality. We
      suggest that compromising the organization of the ganglia triggers a
      differentiation pathway in a subpopulation of satellite cells, inducing them to
      become myelinating cells with either a CNS or PNS phenotype. Our data provide an
      additional, novel piece in the myelinating cell-precursor puzzle, and lead to the
      concept that cells in the CNS and PNS that function to ensheath neuronal cell
      bodies and axons can differentiate into OLs, SCs and astrocytes. In sum, it
      appears that glial fate might be determined over and above the CNS/PNS dichotomy.
      Last, we suggest that primordial ensheathing cells form the original cell
      population in which the myelination program first evolved.

PMID- 18634610
TI  - MIND the gap: an astroglial perspective on barrier regulation.
AB  - The blood-brain barrier (BBB) is a specialized tissue interface that provides an
      important homeostatic and immunosurveillance role in the CNS. Unlike most
      microvascular tissues, which readily promote paracellular passage of solutes and
      macromolecules, the BBB is more analogous to polarized mucosal epithelia that
      restrict such permeability in order to prevent disease onset. Recent transgenic
      ablation studies have demonstrated that the BBB and mucosal tissues also share a
      requirement for astroglial-regulated barrier integrity. This review highlights
      the emerging concept that astroglia regulate barrier function at markedly
      different tissue interfaces. It also explores possible lessons that might be
      learnt by adopting epithelial model paradigms of the BBB. For example, novel
      glial-derived S-nitrosylation signals that regulate intestinal permeability in
      the digestive tract might provide new mechanistic insights into the function of
      the BBB. A better understanding of such universal mechanisms for barrier
      regulation will facilitate novel therapeutic strategies that target permeability
      disorders at CNS and mucosal tissue interfaces.

PMID- 18634612
TI  - Reduced EGFR signaling in progenitor cells of the adult subventricular zone
      attenuates oligodendrogenesis after demyelination.
AB  - Neural progenitor cells that express the NG2 proteoglycan are present in
      different regions of the adult mammalian brain where they display distinct
      morphologies and proliferative rates. In the developing postnatal and adult
      mouse, NG2(+) cells represent a major cell population of the subventricular zone
      (SVZ). NG2(+) cells divide in the anterior and lateral region of the SVZ, and are
      stimulated to proliferate and migrate out of the SVZ by focal demyelination of
      the corpus callosum (CC). Many NG2(+) cells are labeled by GFP-retrovirus
      injection into the adult SVZ, demonstrating that NG2(+) cells actively
      proliferate under physiological conditions and after demyelination. Under normal
      physiological conditions and after focal demyelination, proliferation of NG2(+)
      cells is significantly attenuated in wa2 mice, which are characterized by reduced
      signaling of the epidermal growth factor receptor (EGFR). This results in reduced
      SVZ-to-lesion migration of NG2(+) cells and oligodendrogenesis in the lesion.
      Expression of vascular endothelial growth factor (VEGF) and EGFR ligands, such as
      heparin binding-EGF and transforming growth factor alpha, is upregulated in the
      SVZ after focal demyelination of the CC. EGF-induced oligodendrogenesis and
      myelin protein expression in wild-type SVZ cells in culture are significantly
      attenuated in wa2 SVZ cells. Our results demonstrate that the response of NG2(+)
      cells in the SVZ and their subsequent differentiation in CC after focal
      demyelination depend on EGFR signaling.

PMID- 18634611
TI  - Connexin and pannexin mediated cell-cell communication.
AB  - In this review, we briefly summarize what is known about the properties of the
      three families of gap junction proteins, connexins, innexins and pannexins,
      emphasizing their importance as intercellular channels that provide ionic and
      metabolic coupling and as non-junctional channels that can function as a
      paracrine signaling pathway. We discuss that two distinct groups of proteins form
      gap junctions in deuterostomes (connexins) and protostomes (innexins), and that
      channels formed of the deuterostome homologues of innexins (pannexins) differ
      from connexin channels in terms of important structural features and activation
      properties. These differences indicate that the two families of gap junction
      proteins serve distinct, complementary functions in deuterostomes. In several
      tissues, including the CNS, both connexins and pannexins are involved in
      intercellular communication, but have different roles. Connexins mainly
      contribute by forming the intercellular gap junction channels, which provide for
      junctional coupling and define the communication compartments in the CNS. We also
      provide new data supporting the concept that pannexins form the non-junctional
      channels that play paracrine roles by releasing ATP and, thus, modulating the
      range of the intercellular Ca(2+)-wave transmission between astrocytes in
      culture.

PMID- 18634613
TI  - Events at the transition between cell cycle exit and oligodendrocyte progenitor
      differentiation: the role of HDAC and YY1.
AB  - The complexity of the adult brain is the result of an integrated series of
      developmental events that depends on appropriate timing of differentiation. The
      importance of transcriptional regulatory networks and epigenetic mechanisms of
      regulation of gene expression is becoming increasingly evident. Among these
      mechanisms, previous work has revealed the importance of histone deacetylation in
      oligodendrocyte differentiation. In this manuscript we define the region of
      interaction between transcription factor Yin-Yang 1 (YY1) and histone deacetylase
      1, and characterize the functional consequences of YY1 overexpression on the
      differentiation of oligodendrocyte progenitors.

PMID- 18634615
TI  - The effects of aging, injury and disease on microglial function: a case for
      cellular senescence.
AB  - Neuroinflammation resulting from chronic reactive microgliosis is thought to
      contribute to age-related neurodegeneration, as well as age-related
      neurodegenerative diseases, specifically Alzheimer's disease (AD). Support of
      this theory comes from studies reporting a progressive, age-associated increase
      in microglia with an activated phenotype. Although the underlying cause(s) of
      this microglial reactivity is idiopathic, an accepted therapeutic strategy for
      the treatment of AD is inhibition of microglial activation using anti
      inflammatory agents. Although the effectiveness of anti-inflammatory treatment
      for AD remains equivocal, microglial inhibition is being tested as a potential
      treatment for additional neurodegenerative disorders including amyotrophic
      lateral sclerosis and Parkinson's disease. Given the important and necessary
      functions of microglia in normal brain, careful evaluation of microglial function
      in the aged brain is a necessary first step in targeting more precise treatment
      strategies for aging-related neurodegenerative diseases. Studies from our
      laboratory have shown multiple age-related changes in microglial morphology and
      function that are suggestive of cellular senescence. In this manuscript, we
      review current knowledge of microglia in the aging brain and present new,
      unpublished work that further supports the theory that microglia experience an
      age-related decline in proliferative function as a result of cellular senescence.

PMID- 18634614
TI  - Mast cells can contribute to axon-glial dissociation and fibrosis in peripheral
      nerve.
AB  - Expression of the human epidermal growth factor receptor (EGFR) in murine Schwann
      cells results in loss of axon-Schwann cell interactions and collagen deposition,
      modeling peripheral nerve response to injury and tumorigenesis. Mast cells
      infiltrate nerves in all three situations. We show that mast cells are present in
      normal mouse peripheral nerve beginning at 4 weeks of age, and that the number of
      mast-cells in EGFR(+) nerves increases abruptly at 5-6 weeks of age as axons and
      Schwann cells dissociate. The increase in mast cell number is preceded and
      accompanied by elevated levels of mRNAs encoding the mast-cell chemoattractants
      Rantes, SCF and VEGF. Genetic ablation of mast cells and bone marrow
      reconstitution in W(41) x EGFR(+) mice indicate a role for mast cells in loss of
      axon-Schwann cell interactions and collagen deposition. Pharmacological
      stabilization of mast cells by disodium cromoglycate administration to EGFR(+)
      mice also diminished loss of axon-Schwann cell interaction. Together these three
      lines of evidence support the hypothesis that mast cells can contribute to
      alterations in peripheral nerves.

PMID- 18634616
TI  - The relationship between elderly suicide rates and the affordability of
      psychotropic drugs.

PMID- 18634617
TI  - Mental health reform: Europe at the cross-roads.

PMID- 18634618
TI  - Addressing legal and political barriers to global pharmaceutical access: options
      for remedying the impact of the Agreement on Trade-Related Aspects of
      Intellectual Property Rights (TRIPS) and the imposition of TRIPS-plus standards.
AB  - Despite myriad programs aimed at increasing access to essential medicines in the
      developing world, the global drug gap persists. This paper focuses on the major
      legal and political constraints preventing implementation of coordinated global
      policy solutions - particularly, the Agreement on Trade-Related Aspects of
      Intellectual Property Rights (TRIPS) and bilateral and regional free trade
      agreements. We argue that several policy and research routes should be taken to
      mitigate the restrictive impact of TRIPS and TRIPS-plus rules, including greater
      use of TRIPS flexibilities, advancement of human rights, and an ethical framework
      for essential medicines distribution, and a broader campaign that debates the
      legitimacy of TRIPS and TRIPS-plus standards themselves.

PMID- 18634619
TI  - Willingness to pay for alternative policies for patients with Alzheimer's
      Disease.
AB  - This paper focuses on eliciting the willingness to pay (WTP) for policy measures
      aimed at improving the health care offered to patients suffering from Alzheimer's
      disease (AD). We utilize a discrete choice experiment (DCE) approach for the
      elicitation of the preferences of the general population for three alternative
      policies: home care, day care centres, and medium or long-stay centres. The
      results show that these policies are significantly valued across the surveyed
      population. The monthly WTP per hour of home care is estimated as 4 euros per
      individual, while the monthly WTP values for full population coverage in day
      centres and medium-long-stay centres are estimated as 0.43 euros and 0.42 euros
      respectively. We compare the results of classical and Bayesian estimation
      methods, and conclude that the latter provide a better representation of the
      heterogeneity in the sample. The results are significant for health care, as they
      enable policymakers to identify the social demand for such services, as well as
      the relative economic values placed on the alternative policy measures.

PMID- 18634620
TI  - Valuing lives and life years: anomalies, implications, and an alternative.
AB  - Many government interventions seek to reduce the risk of death. The value of
      preventing a fatality (VPF) is the monetary amount associated with each
      statistical death that an intervention can be expected to prevent. The VPF has
      been estimated using a preference-based approach, either by observing market
      behaviour (revealed preferences) or by asking hypothetical questions that seek to
      replicate the market (stated preferences). The VPF has been shown to differ
      across and within these methods. In theory, the VPF should vary according to
      factors such as baseline and background risk, but, in practice, the estimates
      vary more by theoretically irrelevant factors, such as the starting point in
      stated preference studies. This variation makes it difficult to choose one unique
      VPF. The theoretically irrelevant factors also affect the estimates of the
      monetary value of a statistical life year and the value of a quality-adjusted
      life year. In light of such problems, it may be fruitful to focus more research
      efforts on generating the VPF using an approach based on the subjective well
      being associated with different states of the world.

PMID- 18634621
TI  - Consumer-directed health care: promise or puffery?
AB  - Consumer-directed health care (CDHC) is one of the basic ideas that has emerged
      in recent years as a way of bringing greater efficiency and cost control into
      health care. Its principal aims are to give patients greater control over their
      care, economically as well as medically, and to improve competition among
      providers to increase the range of patient control. Its roots are American,
      bespeaking a cultural suspicion of government, a worry about rising costs, and an
      appeal to the popularity of choice in almost all matters, now including health
      care. CDHC also bespeaks the ideology of market ideology, drawing on both market
      concepts in economics and a push by American conservatives (particularly
      President George W. Bush) to privatize as much of American health care as
      possible). It draws particularly on the business community as a source of ideas
      and inspiration, assuming that if choice and competition work well in the
      commercial sector, it will work equally well in health care. A fundamental
      question, however, is not simply how well business models might work, but also
      whether thinking of the patient as a savvy consumer could ever make full sense in
      the face of complicated, emotionally charged illnesses and complex decision
      making situations. Skepticism is in order.

PMID- 18634622
TI  - Aid, truth, and policy: what do we know?

PMID- 18634623
TI  - Dealing with the medical axis-of-power: the case of Japan.

PMID- 18634624
TI  - Nursing home performance in resident care in the United States: is it only a
      matter of for-profit versus not-for-profit?
AB  - Poorer resident care in US for-profit relative to not-for-profit nursing homes is
      usually blamed on the profit motive. But US nursing home performance may relate
      to Medicaid public financing in a manner qualifying the relationship between
      ownership and quality. We investigated effects of Medicaid resident census,
      Medicaid payment, and occupancy on performance. Resource dependence theory
      implies these predictors may affect discretion in resources invested in resident
      care across for-profit and not-for-profit facilities. Models on physical
      restraint use and registered nurse (RN) staffing were studied using generalized
      estimating equations with panel data derived from certification inspections of
      nursing homes. Restraint use increased and RN staffing levels decreased among for
      profit and not-for-profit facilities when the Medicaid census increased and
      Medicaid payment decreased. Interaction effects supported a theory that
      performance relates to available discretion in resource allocation. Effects of
      occupancy appear contingent on the dependence on Medicaid. Poorer performance
      among US for-profit nursing homes may relate to for-profit homes having lower
      occupancy, higher Medicaid census, and operating in US states with lower Medicaid
      payments compared to not-for-profit homes. Understanding the complexity of
      factors affecting resources expended on resident care may further our
      understanding of the production of quality in nursing homes, whether in the US or
      elsewhere.

PMID- 18634625
TI  - Public-Private Partnerships in the health sector: the Danish experience.
AB  - This article investigates the current use of Public-Private Partnerships (PPP) in
      the Danish health sector based on an initial discussion of theoretical approaches
      that analyze PPP. The empirical analysis concludes that PPP has been used very
      sparsely in the Danish health sector. There are few examples of large-scale
      partnership projects with joint investment and risk taking, but a number of
      smaller partnerships such as jointly owned companies at the regional level. When
      defining PPP more broadly, we can identify a long tradition for various types of
      collaboration between public and private actors in health care in Denmark. An
      analysis of the regulatory environment is offered as an explanation for the
      limited use of PPPs in Denmark. Major political and institutional actors at the
      central level differ in their enthusiasm for the PPP concept, and the regulatory
      framework is somewhat uncertain. A number of general issues and concerns related
      to PPPs are also discussed. It is suggested that a risk-based framework can be
      useful for mapping the potential and challenges for both private and public
      partners. Such a framework can be used to feed into game theoretical models of
      pros and cons for PPP projects. In general terms, it is concluded that more
      empirical research is needed for the assessment of the various risk factors
      involved in using PPPs in health care. Most PPPs are still very young, and the
      evidence on performance and broader governance issues is only just emerging.
      Ideally, such assessments should include comparisons with a purely public
      alternative.

PMID- 18634626
TI  - Aging, health expenditure, proximity to death, and income in Finland.
AB  - This study revisits the debate on the 'red herring', i.e. the claim that
      population aging will not have a significant impact on health care expenditure
      (HCE), using a Finnish data set. We decompose HCE into several components and
      include both survivors and deceased individuals into the analyses. We also
      compare the predictions of health expenditure based on a model that takes into
      account the proximity to death with the predictions of a naive model, which
      includes only age and gender and their interactions. We extend our analysis to
      include income as an explanatory variable. According to our results, total
      expenditure on health care and care of elderly people increases with age but the
      relationship is not as clear as is usually assumed when a naive model is used in
      health expenditure projections. Among individuals not in long-term care, we found
      a clear positive relationship between expenditure and age only for health centre
      and psychiatric inpatient care. In somatic care and prescribed drugs, the
      expenditure clearly decreased with age among deceased individuals. Our results
      emphasize that even in the future, health care expenditure might be driven more
      by changes in the propensity to move into long-term care and medical technology
      than age and gender alone, as often claimed in public discussion. We do not find
      any strong positive associations between income and expenditure for most non-LTC
      categories of health care utilization. Income was positively related to
      expenditure on prescribed medicines, in which cost-sharing between the state and
      the individual is relatively high. Overall, our results indicate that the future
      expenditure is more likely to be determined by health policy actions than
      inevitable trends in the demographic composition of the population.

PMID- 18634627
TI  - Systematic reviews--do they 'work' in informing decision-making around health
      inequalities?

PMID- 18634628
TI  - Health economics made easy: guiding the initiated and uninitiated.

PMID- 18634629
TI  - Emerging health care reform issues in the US presidential debate.

PMID- 18634630
TI  - Defining hospital markets for antitrust enforcement: new approaches and their
      applicability to The Netherlands.
AB  - Effective antitrust enforcement is of crucial importance for countries with a
      market-based health care system in which hospitals are expected to compete.
      Assessing hospital market power--a central issue to competition policy--is,
      however, complicated because the presence of third party payers and the general
      unobservability of prices make it difficult to apply the standard methods of
      market definition. Alternative, less formal methods historically employed in the
      hospital industry have proven inaccurate; these methods were even called
      inapplicable in a recent US court decision. In this paper, we discuss the
      strengths and weaknesses of several new approaches to defining hospital markets
      that are suggested in the recent economic literature. In particular, we discuss
      the applicability of the time-elasticity approach, competitor-share approach, and
      option-demand approach to the recently partly deregulated Dutch hospital market.
      We conclude that the appropriate approach depends crucially on how health
      insurers contract with hospitals and how patients select their hospital.

PMID- 18634631
TI  - Global public-private partnerships against neglected diseases: building
      governance structures for effective outcomes.
AB  - Focusing on the problem of pharmaceutical R&D for drugs and vaccines against
      neglected diseases in developing countries, this article argues that the
      effectiveness of global health partnerships potentially lies in their capacity to
      address the problem of dual market failures: on a first level they may tackle the
      poverty induced lack of effective demand for health products which impedes the
      creation of market-financed innovative products. On a second level, they may help
      overcoming hold-up problems and underinvestment induced by the complexity of
      neglected diseases R&D. Yet, organizing transactions within a partnership is not
      a panacea against these problems: a crucial determinant of success is proper
      ownership structures. They need to respond to (i) the degree to which the
      respective parties value the partnership outcome, (ii) the relative importance of
      the investment of the parties, and (iii) the nature of the partnership outcome.
      The argument developed in the analysis is built on an integrated framework
      combining insights from incomplete contracting theory and public goods economics.
      It is supported by a preliminary statistical analysis of 17 GHPs.

PMID- 18634632
TI  - Prescription drug co-payments and cost-related medication underuse.
AB  - Co-payments have been linked to the slowing growth in pharmaceutical spending
      over the last five years. However, patients with health problems frequently have
      difficulty affording their pharmacotherapy and fail to take their medication as
      prescribed. We examine the relationship between co-payment amounts and four types
      of cost-related underuse: taking fewer doses, postponing taking a medication,
      failing to fill a prescription at all, and taking medication less frequently than
      prescribed. We conducted a nationwide survey of US adults age 50 and over who
      take medication for a chronic condition. Participants provided information on 17
      chronic conditions, medication they take for those conditions, and whether they
      underused any medication due to cost. We analyzed those who reported paying co
      payments for their prescriptions (n = 2,869). Analysis involved multivariate
      logistic regression, with adjustments for survey weights and clustering. Our data
      show a strong positive association between co-payments and cost-related
      medication underuse. Although people differ in how they underuse medications,
      these behaviours are strongly associated with co-payment amount. Realigning the
      co-payments with cost-effectiveness data, also known as value-based insurance
      design, warrants further investigation.

PMID- 18634633
TI  - Developing methods that really do value the 'Q' in the QALY.
AB  - Most health economists recommend that improvements in health be valued by asking
      members of the general public to imagine themselves in different states of health
      and then to think about how many years of life they would give up or what risk of
      death they would be willing to accept in order to be in full health. In this
      paper, I argue that preferences are not a very good guide to future experiences
      and a more suitable way to value health is to ask people in different states of
      health how they think and feel about their lives. Valuing health in this way may
      result in greater priority being given to mental health services. Whatever the
      precise implications, it is my contention that it is much better to ration health
      care according to real experiences rather than according to hypothetical
      preferences.

PMID- 18634634
TI  - Valuing health properly.
AB  - This comment on Paul Dolan's essay, 'Developing methods that really do value the
      "Q" in the QALY,' seconds his critique of current preference-based methods of
      valuing health states but disputes both his assumption that health states should
      be appraised by their bearing on well-being and his conclusion that the bearing
      of health states on well-being should be measured in terms of subjective
      experience. This comment defends instead the view that health states should be
      valued in terms of the range of activities that they permit.

PMID- 18634635
TI  - Are subjective well-being measures any better than decision utility measures?
AB  - There are a number of substantial problems with using decision-based utility
      measures such as the time trade off and standard gamble to value improvements in
      health. Dolan (this issue) argues that because of these problems, it would be
      better to use measures of real experiences (subjective well being). We review
      evidence that supports criticisms of decision-based utility measures, whether
      provided by patients or non-patients. But we also review a number of substantial
      problems with currently used measures of subjective well-being, and point out
      that there is no definitive evidence that they represent any improvement over
      decision utility measures. We conclude with a call for expanded research into
      developing new tools for quantifying health-related quality of life that are more
      valid, more sensitive to changes in health status, and less biased.

PMID- 18634636
TI  - In defence of subjective well-being.

PMID- 18634638
TI  - Physicians' career satisfaction, quality of care and patients' trust: the role of
      community uninsurance.
AB  - There is evidence that health care providers located in communities with
      relatively large uninsured populations face financial difficulties because of low
      service demand and high levels of uncompensated care. Data on 4,920 physicians
      from the 2000-2001 Community Tracking Study Physician Survey and from 25,637
      adults from the 2003 Community Tracking Study Household Survey were used to
      analyze whether the relative size of the local uninsured population is associated
      with the level of career satisfaction and the quality of care provided by
      physicians and to assess whether patient trust is associated with the level of
      community uninsurance. The results indicate that the proportion of uninsured
      adults in a given community is negatively related to physicians' career
      satisfaction and the perceived quality of health care provided. Community
      uninsurance is also negatively related to patient trust in their doctor and
      positively related to whether insured patients believed that their doctor was
      influenced by rules from health insurance companies. Physicians in communities
      with relatively large uninsured populations may have lower career satisfaction
      and lower perceptions of the quality of care provided due to financial
      difficulties. Patients in these communities are also less likely to trust their
      physician.

PMID- 18634639
TI  - Mental health service delivery in Ontario, Canada: how do policy legacies shape
      prospects for reform?
AB  - Like many jurisdictions, mental health policy-making in Ontario, Canada, has a
      long history of frustrated attempts to move from a hospital and physician-based
      tradition to a coordinated system with greater emphasis on community-based mental
      health care. This study examines policy legacies associated with the introduction
      of psychiatric hospitals in the 1850s and of public health insurance (medicare)
      in the 1960s in Ontario; and their effect on subsequent mental health reform
      initiatives using a qualitative case study approach. Following Pierson (1993) we
      capture the resource/incentive and interpretive effects of prior policies on
      three groups of actors: government elites, interests, and mass publics. Data are
      drawn from academic and policy literature, and key informant interviews. The
      findings suggest that psychiatric hospital policy produced important policy
      legacies which were reinforced by the establishment of Canadian medicare. These
      legacies explain the traditional difficulty in achieving mental health reform,
      but are less helpful in explaining recent promising developments that support
      community-based care. Current reform of the Ontario health system presents an
      opportunity to overcome several of these legacies. Analysis of policy legacies in
      other countries which had an asylum tradition may help to explain the
      similarities and differences in their subsequent paths of mental health reform.

PMID- 18634640
TI  - The complexity of governance change: reforming the governance of medical
      performance in Germany.
AB  - The governance of medical performance is changing and new governing instruments
      are emerging. Existing analyses highlight the complexity of new governance
      arrangements, but the more or less dualistic perspective limits the possibility
      for exploring more fully this complexity. The present article therefore uses
      recent contributions to the literature on governance to explore the co-existence
      of different forms of governance with the aim of assessing the relative extent
      and the substantive nature of governance change. Using recent reforms of the
      governance of medical performance in Germany as a case study, the analysis
      suggests that the complexity of governance change takes three forms: first, the
      balance among (hybrid) forms of governance is shifting; second, the nature of
      individual (hybrid) forms of governance is changing; and, third, both types of
      change are reflected in tensions not only between but also within (hybrid) forms
      of governance. As such, the article also contributes to the recent literature on
      governance by highlighting the centrality of tensions in contemporary governance,
      which can also occur within both hybrid forms of governance and ;pure' forms of
      governance.

PMID- 18634641
TI  - Specialization and physician-ownership in the US hospital industry: beyond the
      moratorium.
AB  - A moratorium in the US on referrals of Medicare and Medicaid patients to new
      cardiac, orthopedic, or surgical specialty hospitals by physician-investors was
      recently lifted, yet the considerable controversy stirred by this growing
      hospital organizational form continues. This paper calls attention to the
      peculiar trade-offs introduced by entry of these specialty hospitals, and
      highlights distinctions among their different types. New policy approaches should
      be open to the notion that all physician-owned specialty hospitals need not
      necessarily be regulated in the same way. And caution will be required not to
      compromise the capacity of community general hospitals to service more complex
      patients and to maintain the social safety net.

PMID- 18634642
TI  - Activity based financing in England: the need for continual refinement of payment
      by results.
AB  - The English National Health Service is introducing activity based tariff systems
      or Payment by Results (PbR) as the basis for hospital funding. The funding
      arrangements provide incentives for increasing activity, particularly day
      surgery, and, uniquely, are based on costing data from all hospitals. But prices
      should not be based on average costs and the potential of PbR to improve the
      quality of care is yet to be exploited. Without refinement, PbR threatens to
      undermine expenditure control, to divert resources away from primary care, and to
      distort needs based funding.

PMID- 18634643
TI  - Hospital cost differences and payment by results.

PMID- 18634644
TI  - Activity-based payments and reforms of the English hospital payment system.

PMID- 18634645
TI  - Payment by results: qualified ambition?

PMID- 18634646
TI  - Coping accountably in a dangerous world.

PMID- 18634647
TI  - Letter on Calum Paton's 'howl of rage'.

PMID- 18634648
TI  - The political economy of Chinese health reform.

PMID- 18634649
TI  - Who switches sickness funds in Israel?
AB  - A competitive national health insurance system was introduced in Israel in 1995.
      Consumer mobility has been traditionally a signal of market (managed)
      competition. However, since 1998, sickness funds' switching rate has been stable
      at around 1% of the population. The low switching rate is explained by limited
      real options and similarity in the sickness funds functioning, and reluctance to
      change providers. The paper aims to characterize the 1% of the population who
      switches sickness fund in relation to the stayers, and to examine the
      implications for public policy. The National Insurance Institute Health Registry
      was used to conduct two analyses: (i) bivariate comparisons on selected socio
      demographic characteristics of the switchers to those of the stayers in the years
      1999-2000, and (ii) a multivariate logistic analysis of the propensity to switch
      for the entire adult (21+) population in the years 2005-2006. The main result is
      that switching is an inferior good. Both the bivariate and the multivariate
      analysis show that persons with lower labor-income, receiving income support or
      unemployment benefits are more likely to switch. Switchers have more children up
      to age 18. Arabs and Orthodox Jews are more likely to switch sickness funds. The
      1% of switchers does not form a random draw from the age-sex-adjusted population.
      The over-representation of poor persons among switchers is unique to the Israeli
      scene, which might have resulted from demand-side initiatives, but also from
      implicit risk-selection strategies exercised by the sickness funds under the
      Israeli incomplete age-based risk-adjustment system.

PMID- 18634651
TI  - Lawsuit activity, defensive medicine, and small area variation: the case of
      Cesarean sections revisited.
AB  - This paper examines whether delivery practice patterns (Cesarean sections or
      vaginal) are influenced by lawsuits or whether the hypothesized relationship is
      confounded by small area variation. The analysis uses multilevel analysis to deal
      with hospital- and Dartmouth Hospital Referral Region-level variation. The model
      includes patient clinical variables, patient socio-economic status, and hospital
      characteristics as control variables. The secondary data sources include hospital
      discharges from the 2002 Texas Health Care Information Council as well as 1988
      2001 Texas Department of Insurance Closed Claim File data. After extracting the
      variation in delivery practice between hospitals and between Dartmouth Hospital
      Referral Regions in a multilevel model, the effects of lawsuits on defensive
      medicine are reduced but are still significant.

PMID- 18634650
TI  - Funding pharmaceutical innovation through direct tax credits.
AB  - Rising pharmaceutical prices, increasing demand for more effective innovative
      drugs and growing public outrage have heightened criticism of the pharmaceutical
      industry. The public debate has focused on drug prices and access. As a
      consequence, the patent system is being reexamined as an efficient mechanism for
      encouraging pharmaceutical innovation and drug development. We propose an
      alternative to the existing patent system, instead rewarding the innovating firm
      with direct tax credits in exchange for marginal cost pricing. This concept is
      based on the fundamental assumption that innovation that benefits society at
      large may be financed publicly. As an industry which produces a social good
      characterized by high fixed costs, high information and regulatory costs, and
      relatively low marginal costs of production, pharmaceuticals are well-suited to
      such a mechanism. Under this proposal, drug prices fall, consumer surplus
      increases, access is enhanced, and the incentives to innovate are preserved.

PMID- 18634652
TI  - Family history of chronic disease and participation in healthy behaviours.
AB  - This article presents an investigation into whether individuals incorporate
      information on their family genetic (health) endowment into decision making
      regarding participation in behaviours related to the production of health
      capital. Competing theoretical perspectives exist as to how genetic endowment
      should affect participation in health-related behaviours. There is also a growing
      consensus that the availability of genetic information holds important
      consequences for the individual in terms of investment in human capital, the
      pricing and availability of health insurance, and labour market opportunity.
      Therefore, the question of how individuals use the greater availability of
      genetic data is important. Our empirical results indicate that poor genetic
      endowment tends to be associated with a lower probability of participation in
      cigarette smoking, but also a lower probability of participation in regular
      exercise.

PMID- 18634653
TI  - Visible hand or invisible fist? The new market and choice in the English NHS.
AB  - As England (unlike the rest of the UK) retreads the market route in health
      policy, it is worth asking two questions. Firstly, is the government right that
      the 'new market' (as it refuses to call it, except in private seminars) is
      fundamentally different from the 1990 s' internal market which New Labour
      allegedly abolished in 1997? Secondly, given that the new market is clearly not
      characterized by the invisible hand, should we characterize it as steered
      'economically' by a visible (facilitating) hand, on the one hand, or managed
      'politically' by a fist which would like to remain invisible in order to maintain
      its power? This article goes on to examine choice in the new NHS with reference
      to Hirschman (1970), arguing that genuflections to the latter by pro-choice
      advocates such as Le Grand (2003) are just that - genuflections. Hirschman is
      used as a taxi by which to reach a desired destination rather than a stimulus to
      critical reflection, Hirschman-style, upon how 'exit', 'voice', and particular
      combinations of 'exit' and 'voice' may produce perverse outcomes.

PMID- 18634654
TI  - Taking the iron fist a little further.

PMID- 18634655
TI  - Peering through a glass: darkly.

PMID- 18634656
TI  - Politics over economics, fist over hand.

PMID- 18634657
TI  - America's health care dilemma: not a pretty sight.

PMID- 18634658
TI  - EU law and regulation of private health insurance.

PMID- 18634659
TI  - Patient reactions to hospital choice in Norway, Denmark, and Sweden.
AB  - This article is a comparative study of three Scandinavian countries--Norway,
      Denmark, and Sweden--all of which have provided the individual patient with
      extensive rights to choose the hospital where he/she wishes to receive treatment.
      In the paper, we present an analysis of the utilization of the opportunity to
      choose between hospitals in these three countries. The analysis addresses two
      questions: (i) How many patients are exercising the right to choose between
      hospitals in these countries and who is making use of this opportunity? (ii) How
      can we explain the observed utilization pattern? The results of the study reveal
      clear similarities between the three countries and suggest that few patients have
      actually chosen their hospital. However, a gradual increase can be observed over
      the years. Few formal, legislative, or economic barriers exist for patients.
      Instead, limited knowledge amongst patients regarding reforms, combined with
      insufficient support from GPs and limited information, can explain why few
      patients choose to receive care outside of their local region.

PMID- 18634660
TI  - Implementing accountability for reasonableness--the case of pharmaceutical
      reimbursement in Sweden.
AB  - This paper aims to describe the priority-setting procedure for new original
      pharmaceuticals practiced by the Swedish Pharmaceutical Benefits Board (LFN), to
      analyse the outcome of the procedure in terms of decisions and the relative
      importance of ethical principles, and to examine the reactions of stakeholders.
      All the 'principally important' decisions made by the LFN during its first 33
      months of operation were analysed. The study is theoretically anchored in the
      theory of fair and legitimate priority-setting procedures by Daniels and Sabin,
      and is based on public documents, media articles, and semi-structured interviews.
      Only nine cases resulted in a rejection of a subsidy by the LFN and 15 in a
      limited or conditional subsidy. Total rejections rather than limitations gave
      rise to actions by stakeholders. Primarily, the principle of cost-effectiveness
      was used when limiting/conditioning or totally rejecting a subsidy. This study
      suggests that implementing a priority-setting process that fulfils the conditions
      of accountability for reasonableness can result in a priority-setting process
      which is generally perceived as fair and legitimate by the major stakeholders and
      may increase social learning in terms of accepting the necessity of priority
      setting in health care. The principle of cost-effectiveness increased in
      importance when the demand for openness and transparency increased.

PMID- 18634661
TI  - Supplementary health insurance as a tool for risk-selection in mandatory basic
      health insurance markets.
AB  - As the share of supplementary health insurance (SI) in health care finance is
      likely to grow, SI may become an increasingly attractive tool for risk-selection
      in basic health insurance (BI). In this paper, we develop a conceptual framework
      to assess the probability that insurers will use SI for favourable risk-selection
      in BI. We apply our framework to five countries in which risk-selection via SI is
      feasible: Belgium, Germany, Israel, the Netherlands, and Switzerland. For each
      country, we review the available evidence of SI being used as selection device.
      We find that the probability that SI is and will be used for risk-selection
      substantially varies across countries. Finally, we discuss several strategies for
      policy makers to reduce the chance that SI will be used for risk-selection in BI
      markets.

PMID- 18634662
TI  - Economists' dream or nightmare? Maximizing health gains from available resources
      using the NICE guidelines.

PMID- 18634663
TI  - NICE: a nightmare worth having?

PMID- 18634664
TI  - A response to Birch and Gafni--some reasons to be cheerful about NICE.

PMID- 18634666
TI  - Organizational innovations and health care decentralization: a perspective from
      Spain.
AB  - Recent policy developments in public health care systems lead to a greater
      diversity in health care. Decentralization, either geographically or at an
      institutional level, is the key force, because it encourages innovation and local
      initiatives in health care provision. The devolution of responsibilities allows
      for a sort of 'deconstruction' of the status quo by changing both organizational
      forms and service provision. The new organizations enjoy greater freedom in the
      way they pay their staff, and are judged according to the results. These
      organizations may retain financial surpluses, develop 'spin-off' companies, and
      commission a range of specialized services (such as Diagnostic and Treatment
      Centres in UK) from providers outside the institutional setting in order to have
      more access to capital markets. However, this diversity may generate a feeling of
      a lack of commitment to a national health service and ultimately a loss of social
      cohesion. Through fiscal decentralization to regional authorities or planned
      delegation of financial agreements to providers, financial incentives are more
      explicit and may seem to place profit making above a commitment to better health
      care. An evaluation of the 'myths and realities' of the decentralization process
      is needed. Here, I offer an assessment of the 'pros' and 'cons' of the health
      care decentralization process in Spain, drawing on the experience of regional
      reforms from the pioneering organizational innovations implemented in Catalonia
      in 1981, up to the currently observed dispersion of health care spending per
      capita across the regions.

PMID- 18634667
TI  - The American right-wing policy agenda.

PMID- 18634668
TI  - EU law and national health policies: problem or opportunity?

PMID- 18634669
TI  - Financial incentives and psychiatric services in Australia: an empirical analysis
      of three policy changes.
AB  - Australia has a national, compulsory and universal health insurance scheme,
      called Medicare. In 1996 the Government changed the Medicare Benefit Schedule
      Book in such a way as to create different financial incentives for consumers or
      producers of out-of-hospital private psychiatric services, once an individual
      consumer had received 50 such services in a 12-month period. The Australian
      Government introduced a new Item (319) to cover some special cases that were
      affected by the policy change. At the same time, the Commonwealth introduced a
      'fee-freeze' for all medical services. The purpose of this study is two-fold.
      First, it is necessary to describe the three policy interventions (the
      constraints on utilization, the operation of the new Item and the general 'fee
      freeze'.) The new Item policy was essentially a mechanism to 'dampen' the effect
      of the 'constraint' policy, and these two policy changes will be consequently
      analysed as a single intervention. The second objective is to evaluate the policy
      intervention in terms of the (stated) Australian purpose of reducing utilization
      of psychiatric services, and thus reducing financial outlays. Thus, it is
      important to separate out the different effects of the three policies that were
      introduced at much the same time in November 1996 and January 1997. The
      econometric results indicate that the composite policy change (constraining
      services and the new 319 Item) had a statistically significant effect. The
      analysis of the Medicare Benefit (in constant prices) indicates that the 'fee
      freeze' policy also had a statistically significant effect. This enables separate
      determination of the several policy changes. In fact, the empirical results
      indicate that the Commonwealth Government underestimated the 'savings' that would
      arise from the 'constraint' policy.

PMID- 18634671
TI  - Regionalization versus competition in complex cancer surgery.
AB  - The empirical association between high hospital procedure volume and lower
      mortality rates has led to recommendations for the regionalization of complex
      surgical procedures. While regionalization may improve outcomes, it also reduces
      market competition, which has been found to lower prices and improve health care
      quality. This study estimates the potential net benefits of regionalizing the
      Whipple surgery for pancreatic cancer patients. We confirm that increased
      hospital volume and surgeon volume are associated with lower inpatient mortality
      rates. We then predict the price and outcome consequences of concentrating
      Whipple surgery at hospitals that perform at least two, four, and six procedures
      respectively per year. Our consumer surplus calculations suggest that
      regionalization can increase consumer surplus, but potential price increases
      extract over half of the value of reduced deaths from regionalization. We reach
      three conclusions. First, regionalization can increase consumer surplus, but the
      benefits may be substantially less than implied by examining only the outcome
      side of the equation. Second, modest changes in outcomes due to regionalization
      may lead to decreases in consumer surplus. Third, before any regionalization
      policy is implemented, a deep and precise understanding of the nature of both
      outcome/volume and price/competition relationships is needed.

PMID- 18634670
TI  - Medicaid policy changes in mental health care and their effect on mental health
      outcomes.
AB  - In recent years, Medicaid has experienced a dramatic increase in spending on
      prescription drugs in general and psychotropic medications in particular. The
      purpose of this study is to examine the effects of increased Medicaid spending on
      psychotropic drugs on improving the mental health and well-being of participants
      at the population level. Specifically, we study the effect on outcomes that are
      strongly correlated with mood disorders, including depression and Attention
      Deficit/Hyperactivity disorder, controlling for concomitant increases in Medicaid
      eligibility thresholds and expansion into managed care for mental health
      services. Knowledge of the effects of changes in the Medicaid program is crucial
      to policymakers as they consider implementing and expanding mental health
      services. Our results show that increased spending on antidepressants and
      stimulants are associated with improvements in some outcomes, but not in others.

PMID- 18634672
TI  - A new approach to the comparative analysis of health systems: invasive treatment
      for heart disease in the US, France, and their two world cities.
AB  - Cross-national comparisons that assess dimensions of health system performance
      indicate that the US provides higher rates of revascularization procedures than
      France and other developed nations, but we believe these findings are misleading.
      In this paper, we compare the use of these procedures in the US, France and their
      two world cities, Manhattan and Paris. In doing so, we address a number of
      limitations associated with existing cross-national comparisons of heart disease
      treatment. After adjusting for the prevalence of disease in these nations and
      cities, we found that residents of France aged 45-64 years receive more
      revascularization procedures than residents of the US and that Parisians receive
      more revascularizations than residents of Manhattan. Older residents 65 years and
      over (65+) in the US receive more of these procedures than their French
      counterparts, but the differences are not nearly as great as previous studies
      suggest. Moreover, our data on Manhattan and Paris where the population and level
      of health resources are more comparable, indicate that older Parisians obtain
      more revascularization procedures than older Manhattanites. Finally, we found
      that the use of revascularization procedures is significantly lower in Manhattan
      among persons without private health insurance and among racial and ethnic
      minorities.

PMID- 18634673
TI  - Inconsistent objectives--reflections on some selective health care policy
      developments in Europe.
AB  - Over the last two decades, there has been an increased focus among the health
      policy and research communities upon improving efficiency, in terms of activity
      levels and health outcomes, in the health care systems of the EU member states.
      In this article, some of these developments are described and to some extent
      assessed, and an attempt is made to highlight how they may serve to undermine
      more fundamental aspects of these systems: namely, that access to health care be
      universal and affordable at the point of use.

PMID- 18634674
TI  - The hedgehog and the fox: Glouberman and Marmor on 'healthy public policy'.

PMID- 18634675
TI  - Academia, policy and politics.

PMID- 18634676
TI  - Measuring the globalization of health services: a possible index of openness of
      country health sectors to trade.
AB  - Globalization is a key challenge facing health policy-makers. A significant
      aspect of this is trade in health services. However, little is currently known
      about how trade in health services will affect the health of populations and
      national economies. A key determinant of the impact of trade in health services
      will be the general economic and trade context of the country concerned. One
      specific aspect of this is the 'openness' of a country's health sector to trade;
      yet there is little, if anything, currently known about the most appropriate
      methods to assess openness of the health sector.

PMID- 18634677
TI  - Structure and logic of regulation and governance of quality of health care: was
      OFSTED a model for the Commission for Health Improvement?
AB  - The Labour Government elected in 1997 faced similar problems in health care to
      those faced by the Conservative Government in schools in the early 1990s. And the
      policies developed for health care in the late 1990s echoed those that had been
      implemented for schools. This paper considers one of those common policies,
      namely the creation of new central inspectorates required to visit all
      organizations over a four-year period: the Office for Standards in Education
      (OFSTED) to inspect the quality of teaching in schools, and the Commission for
      Health Improvement (CHI) to review the implementation of the systems and
      processes of clinical governance in every organization in the National Health
      Service (NHS). At its creation, CHI was described as an OFSTED for the NHS. This
      paper compares these two inspectorates; describes origins of policies and
      institutions; considers their rhetoric and practices; describes the processes the
      two organizations used and considers their impacts. It argues that structural
      differences meant that CHI could never have been an OFSTED for the NHS;
      relational distance is a key aspect of inspection/regulation; and that the key to
      effective regulation in the case of the NHS was the relational proximity between
      CHI and the NHS, with the added weight of a strong performance management regime.

PMID- 18634678
TI  - Patient empowerment and the introduction of hospital choice in Denmark and
      Norway.
AB  - This article provides a critical analysis of the introduction of hospital choice
      in Denmark and Norway. The two Nordic cases provide evidence from public
      integrated health systems that may be compared to the current implementation of
      choice in other countries such as England. We use the theoretical concepts of
      institutional structure, historical legacies, and situational factors to analyze
      the translation of the general choice idea into a specific health policy design
      in Denmark and Norway. The results of the study show that even if there are many
      similarities between the two countries, there are also significant differences.
      In Denmark the initial implementation of choice was adjusted to the dominant
      policy objectives of macroeconomic control through regional planning, while in
      Norway the chosen solution reflects a more limited concern for expenditure
      control and a greater willingness to experiment. Timing and differences in the
      relative strength of the decentralized actors are important explanatory factors.
      Theoretically, this article provides some insights into the problem of
      introducing policies that contradict existing traditions, norms, and values. It
      addresses issues of policy design and the relationship between ideas,
      historically developed institutions, and situational factors, including actor
      constellations and interests.

PMID- 18634679
TI  - The determinants of policy for population health.
AB  - Many advocates of policy to implement the findings of research on the multiple
      determinants of health accord scant attention to the determinants of health
      policy in democratic countries. The principle determinants of the allocation of
      scarce resources to improving health include: the priorities of voters; the
      diffusion of responsibility for improving health; the absence of evidence about
      matters of consequence to policy makers; the arraying of some evidence in ways
      that frustrate policy making; resistance to addressing determinants other than
      clinical services and traditional public health practices among many
      professionals in these fields, as well as by industries that supply the health
      sector; and the special political influence of persons who suffer serious chronic
      disease and of members of their families.

PMID- 18634680
TI  - Health determinants, policy indeterminacy?

PMID- 18634681
TI  - The 'long and lonely road': translating evidence into policy.

PMID- 18634682
TI  - The 'long and lonely road': translating evidence into policy reply.

PMID- 18634684
TI  - Transformation of the US Veterans Health Administration.

PMID- 18634685
TI  - Solidarity in competitive health insurance markets: analysing the relevant EC
      legal framework.
AB  - In this article we perform an economic analysis of different regulatory
      frameworks that aim at guaranteeing solidarity in competitive health insurance
      markets. Thereafter, we analyse the legal conformity of these intervention
      strategies with EC law. We find that risk compensation schemes are the first-best
      intervention strategy because they guarantee an 'acceptable level of solidarity'
      without hindering free trade and competition and without reducing efficiency.
      Second-best options are premium and excess-loss compensation schemes, which
      guarantee solidarity at the expense of some efficiency. Premium rate restrictions
      and open enrolment should be avoided because they reduce efficiency and are
      unnecessary, not proportional, and undesirable to the pursuit of the general
      good. These conclusions are relevant for EU countries that adopt premium rate
      restrictions and open enrolment in combination with a risk compensation scheme,
      such as Ireland and the Netherlands. In these countries policy makers should
      design the health insurance schemes in conformity with EC law, for example by
      replacing premium rate restrictions and open enrolment with premium and/or excess
      loss compensation schemes.

PMID- 18634686
TI  - Conceptualizing decentralization in European health systems: a functional
      perspective.
AB  - Although decentralization has been widely implemented in health systems, there is
      little agreement as to how it should be defined or the outcomes it should
      produce. This article develops a functional typology based on political,
      administrative, and fiscal dimensions of decentralization. It utilizes these
      three categories to identify and highlight key theoretical issues concerning
      decentralization, emphasizing the likely advantages and disadvantages that
      decentralization can be expected to generate. It then examines the usefulness of
      this functional framework in explaining recent policy-making decisions within a
      number of tax-based health systems in Western Europe. The article concludes by
      suggesting that this three-part typology can be helpful to both policy makers and
      academics in evaluating the effectiveness of decentralization as a policy
      mechanism within health care systems.

PMID- 18634687
TI  - Public involvement policies in health: exploring their conceptual basis.
AB  - Despite its obvious appeal, the concept of public involvement is poorly defined
      and its rationale and objectives are rarely specified when applied to current
      health policy contexts. This paper explores some of the underlying concepts,
      definitions, and issues underpinning public involvement policies and proposes a
      set of criteria and questions that need to be addressed to allow for the
      evaluation of public involvement strategies and their impact on the health policy
      process. It aims to further our understanding of the role that public involvement
      may play in contributing to health systems that are responsive to the needs and
      priorities of the public, and, ultimately, providing better health and health
      care services to the community at large.

PMID- 18634688
TI  - Effect of the implementation of an enterprise-wide Electronic Health Record on
      productivity in the Veterans Health Administration.
AB  - Since 1995, the Veterans Health Administration (VHA) has had an ongoing process
      of systems improvement that has led to dramatic improvement in the quality of
      care delivered. A major component of the redesign of the VHA has been the
      creation of a fully developed enterprise-wide Electronic Health Record (EHR).
      VHA's Health Information Technology was developed in a collaborative fashion
      between local clinical champions and central software engineers. Successful
      national EHR implementation was achieved by 1999, since when the VHA has been
      able to increase its productivity by nearly 6 per cent per year.

PMID- 18634689
TI  - The case for risk-based premiums in public health insurance.
AB  - Uniform, risk-independent insurance premiums are accepted as part of 'managed
      competition' in health care. However, they are not compatible with optimality of
      health insurance contracts in the presence of both ex ante and ex post moral
      hazard. They have adverse effects on insurer behaviour even if risk adjustment is
      taken into account. Risk-based premiums combined with means-tested, tax-financed
      transfers are advocated as an alternative.

PMID- 18634690
TI  - Response: Is there a case for risk-based premiums in health care insurance?

PMID- 18634691
TI  - Response: The case for risk-based subsidies in public health insurance.

PMID- 18634693
TI  - Better regulation in troubled times.

PMID- 18634694
TI  - Does it really matter where you live? A panel data multilevel analysis of Swedish
      municipality-level social capital on individual health-related quality of life.
AB  - We test whether individual health status is related to area-level social capital
      measured by rates of voting participation in municipal political elections,
      controlling for personal characteristics, where health status is measured by
      mapping responses to interview survey questions into the generic health-related
      quality of life measure (HRQoL) the EQ-5D in order to derive the health state
      scores. The analysis is based on unbalanced panel data from Statistic Sweden's
      Survey of Living Conditions (the ULF survey) and a 3-level multilevel regression
      analysis, where level 1 consists of a total of 31,585 observations for 24,419
      individuals at level 2 nested within 275 Swedish municipalities at level 3. We
      find that the health state scores increase significantly with municipality
      election rates. This result is robust to a number of measurement and
      specification issues explored in a sensitivity analysis. However, almost all
      variation in health status exists across individuals (more than 98%), which
      demonstrates that even if social capital (and other contextual variables) may be
      significant it is of less importance, at least at the municipality level in
      Sweden.

PMID- 18634695
TI  - Pursuing cost containment in a pluralistic payer environment: from the aftermath
      of Clinton's failure at health care reform to the Balanced Budget Act of 1997.
AB  - Following a decade in which Medicare operated as the leading 'change agent'
      within the US health care system, the private sector rose to the fore in the mid
      1990s. The failure of President Clinton's attempt at comprehensive, public sector
      led reform left managed care as the solution for cost control. And for a period
      it worked, largely because managed care organizations were able to both squeeze
      payments to selective networks of medical providers and significantly reduce
      inpatient hospital stays. There was a lot of 'fat' in the nation's convoluted
      health care system that could be (and was) eliminated through competitive
      negotiations between medical providers and insurers, employers, or managed care
      organizations. One of our primary arguments in this article is that managed care
      operated partly as a systematic suppression of price discrimination or
      differential pricing (often referred to as 'cost shifting'), as managed care
      organizations qua purchasing agents prevented hospitals and physicians from
      summarily raising prices to private payers to meet their financial requirements.
      Over time, however, managed care fell victim to inflated expectations, its own
      initial success, and larger fiscal forces. During this same period, Republicans
      and Democrats struggled to reach a consensus over the future direction of
      Medicare. Their disagreements contributed to the impasse over budget policy in
      1995 and the infamous partial federal government shutdown. After President
      Clinton's reelection in 1996, partisan disagreements over Medicare dissipated.
      And, in 1997, Congress and the president passed the Balanced Budget Act of 1997,
      which emerged as a massive piece of patchwork legislation that sought to balance
      the federal budget, rein in Medicare spending, and increase the number of the
      programme's beneficiaries in private health plans.

PMID- 18634696
TI  - Acquisition and disclosure of genetic information under alternative policy
      regimes: an economic analysis.
AB  - A current policy issue is whether, and if so under what circumstances, insurance
      companies should be given access to genetic test results. The insurance industry
      argues for mandatory disclosure in order to avoid problems of adverse selection;
      an alternative would be a moratorium or legislation preventing such disclosure; a
      third option a voluntary disclosure law. This paper investigates the impact of
      these policies on individuals' incentives to both acquire genetic information and
      to disclose it to providers of health and/or life insurance. The theoretical
      framework used to inform this analysis is provided by the 'games of persuasion'
      literature, in which one agent tries to influence another agent's decision by
      selectively withholding her private information regarding quality. The
      application of the theoretical framework to this policy context yields the
      following results. Individuals have the incentive to acquire genetic information
      and to disclose the test results if disclosure is voluntary. If, however, they
      are obliged to disclose the results of any genetic tests they have taken, their
      incentive may be not to acquire such information. I discuss the policy
      implications of these findings both from the point of view of the insurance
      industry and from a public health perspective.

PMID- 18634697
TI  - The private-public mix of healthcare: evidence from a decentralised NHS country.
AB  - Privatizations of public services are often driven by economic scarcity and
      changes in political leadership, in particular election victories for
      conservative or neoliberal political parties. Data from Norwegian counties on
      numbers of medical specialists in secondary care over a period of 11 years (1991
      2001) allow us to analyse effects of economic, socioeconomic, and political
      factors on supply of both public and private specialists and the private-public
      mix. We find striking variations between the main explanatory factors related to
      public and private supply. Supply of public specialists is explained by counties'
      revenue levels and demographic factors and is not affected by the party
      composition of councils. The supply of private specialist medical services is
      negatively related to the proportion of elderly patients. The scarcity hypothesis
      is confirmed as lower county revenue levels increase both the absolute and
      relative proportions of private supply. Political composition of councils affects
      the private proportion of medical specialists as increased representation of
      conservatives leads to privatization.

PMID- 18634698
TI  - NICE's use of cost effectiveness as an exemplar of a deliberative process.
AB  - This paper seeks to test 12 conjectures about the predicted use of deliberative
      processes by applying them to the technology assessment procedures used by the
      National Institute for Health and Clinical Excellence (NICE) in England and
      Wales. A deliberative process is one that elicits and combines evidence of
      different kinds and from different sources in order to develop guidance - in the
      present case, guidance for a health care system. A deliberative process entails
      the integration of three kinds of evidence: scientific context-free evidence
      about the general clinical potential of a technology, scientific context
      sensitive evidence about particular evidence in realistic scenarios, and
      colloquial evidence to fit context-free scientific evidence into a context and to
      supply the best evidence short of scientific evidence to fill in any relevant
      gaps. It is shown that NICE's appraisals procedures and, in particular, its
      approach to cost effectiveness, entail both the weighing of each of these types
      of evidence and can be seen as rational responses to the 12 conjectures.

PMID- 18634699
TI  - Health policy. Editorial.
AB  - Health policy is one of the most debated and analysed areas of social policy
      internationally, and encompasses a multitude of seemingly disparate but in fact
      largely interrelated issues. For example, how should we motivate doctors to
      improve performance? What is 'performance', and how do we measure it? What is the
      impact of antitrust law on provider behaviour? How do we ensure that we attain
      the most benefit from our health care resources? What is 'benefit', why is it
      defined in the ways that it is, and how do we measure it? Can the implementation
      of World Trade Organization regulations produce legislation that favours public
      sector health care development?

PMID- 18634700
TI  - Does greater Medicare HMO enrollment cause adverse selection into Medigap?
AB  - This paper examines the interaction between public and private insurance in the
      context of the US Medicare program, which serves those aged 65 and older as well
      as the disabled who meet specific eligibility requirements. Specifically, the
      paper examines the extent to which increasing enrollment in Medicare managed care
      (which provides more comprehensive coverage than basic Medicare) influences
      premiums in the privately purchased Medicare supplemental insurance market
      (called 'Medigap'). We employ a fixed effects instrumental variables approach to
      analyze the association between premiums charged by two large Medigap insurers
      and Medicare HMO penetration rates, examining over 60 geographic areas during the
      period 1994-2000. It is hypothesized that greater Medicare HMO penetration will
      lead to adverse selection into the Medigap market, resulting in higher premiums.
      The findings suggest a moderate upward effect on premiums, with elasticities
      ranging from 0.09 to 0.25. Controlling for other factors, moving from a 12% to a
      22% Medicare HMO penetration rate would raise average Medigap premiums from
      $1,314 to $1,615. We discuss the implications of these results with respect to
      the design of national health care systems that include both public and private
      insurers.

PMID- 18634701
TI  - A game theoretic model of drug launch in India.
AB  - There is a popular belief that drug launch is delayed in developing countries
      like India because of delayed transfer of technology due to a 'post-launch'
      imitation threat through weak intellectual property rights (IPR). In fact, this
      belief has been a major reason for the imposition of the Trade Related
      Intellectual Property Rights regime under the WTO. This construct undermines the
      fact that in countries like India, with high reverse engineering capabilities,
      imitation can occur even before the formal technology transfer, and fails to
      recognize the first mover advantage in pharmaceutical markets. This paper argues
      that the first mover advantage is important and will vary across therapeutic
      areas, especially in developing countries with diverse levels of patient
      enlightenment and quality awareness. We construct a game theoretic model of
      incomplete information to examine the delay in drug launch in terms of costs and
      benefits of first move, assumed to be primarily a function of the therapeutic
      area of the new drug. Our model shows that drug launch will be delayed only for
      external (infective/communicable) diseases, while drugs for internal, non
      communicable diseases (accounting for the overwhelming majority of new drug
      discovery) will be launched without delay.

PMID- 18634702
TI  - The trade in human organs in Tamil Nadu: the anatomy of regulatory failure.
AB  - There has been much recent interest in the trade in human organs in India. This
      paper examines both the extent to which regulatory controls through the
      Transplantation of Human Organs Act (1994) are effective in curbing
      commercialization and the nature of the constraints on the effective
      implementation of this Act. The study, a politico-economic analysis of health
      sector regulation, is based on a stakeholder analysis drawing on the views of key
      decision makers, service providers, organ donors and recipients. The findings
      indicate widespread acknowledgement of an organs trade and highlight four major
      constraints on the effective implementation of the Act: the commercial interests
      of middlemen and service providers, the ambiguities and loopholes in the Act; the
      low monitoring capacity of the regulatory authorities, and the pressures and
      responsibilities exerted upon the Authorizing Committees. A feature of the Act is
      that its implementation is subject to a major incentive compatibility constraint 
      it is seemingly not in the interests of any of the key players, including the
      regulatory authorities, to restrict the organ trade. To some extent, this
      institutional problem is created by the specific nature of the regulatory
      intervention, and, as a consequence, measures involving straightforward
      redrafting of the regulation might go some way to addressing this incentive
      problem. Another solution may entail a 'harm-reduction' strategy involving a
      controlled trade where procurement and organ matching is carried out by a
      government agency (this would require, however, the prior resolution of the
      broader ethical question concerning the legitimacy of such trade).

PMID- 18634703
TI  - Cross-national comparisons of human resources for health - what can we learn?
AB  - After a long period of neglect, the issue of human resources for health (HRH) has
      recently emerged as a core component on the international health agenda, with
      policy makers increasingly eager to learn from experience elsewhere. This article
      investigates systematically the opportunities and challenges associated with the
      use of cross-national comparisons of HRH policies and practices. It reviews the
      evidence in favour of using international comparative studies on HRH, discusses
      emerging opportunities for developing a cross-national research agenda to guide
      HRH policies in Europe, and highlights obstacles which may hinder the
      implementation of comparative studies on HRH. While demonstrating many
      opportunities offered by the comparative approach to improve understanding of
      human resources processes in the health sector, this article also emphasizes the
      dangers of simplistic pleas for the transfer of human resource policies without
      taking into account the context-specific factors and the generative capacity of
      the social actors in the design and implementation of policy changes.

PMID- 18634704
TI  - Priority setting in health - a political economy perspective.
AB  - Most countries face high demands on their health care systems and have limited
      resources with which to meet them. Priority setting seeks to address these
      problems by proposing rules to decide which groups of patients or disease areas
      should secure favoured access to limited health care resources. The economic
      approach towards priority setting, particularly in the form of cost-effectiveness
      analysis, is commonly advocated. However, despite many decades of refinement of
      the technical and methodological issues arising from the use of economic
      evaluation in priority setting, decision makers continue to diverge frequently
      from the principles of economic evaluation. Our approach in this paper is to
      highlight the potential contribution of models of political economy to
      understanding what constitutes rational behaviour when agents operate within
      political and institutional constraints. We argue that there may be potentially
      greater benefits to be gained from exploration and analysis of priority setting
      using models based on concepts such as median voter and competing interest
      groups, than from further efforts to refine the techniques of economic
      evaluation.

PMID- 18634706
TI  - Herring ( Clupea harengus) intake influences lipoproteins but not inflammatory
      and oxidation markers in overweight men.
AB  - Fish consumption is associated with a lower incidence of CVD and decreases in
      risk factors for atherosclerosis. Although fish contains other interesting
      components than fish oil, few studies focus on total fish composition and the
      influence food preparation might have on health-beneficial components. In the
      present cross-over intervention study the effect of a 6-week herring diet
      compared with a reference diet on CVD risk factors was investigated. Thirty-five
      healthy, but overweight, men (mean BMI 28.3 kg/m2) were randomised to a 6-week
      herring diet (150 g baked herring fillets/d, 5 d/week) or a reference diet (150 g
      baked lean pork and chicken fillets/d, 5 d/week). Diets were switched after a 12
      week washout period. Plasma total cholesterol, TAG, HDL, HDL2, HDL3, LDL, C
      reactive protein, IL-6, IL-18, intercellular adhesion molecule-1, oxidised LDL,
      oxygen radical absorbance capacity using perchloric acid (ORACPCA), whole-blood
      fatty acids, bleeding time and blood pressure were measured at the beginning and
      end of each dietary period. HDL was significantly higher after the herring diet
      period compared with after the reference diet period: 1.04 v. 0.99 mmol/l. TAG
      decreased after both diets, with no significant difference between the two diets.
      ORACPCA values did not indicate lower concentrations of non-protein plasma
      antioxidants, and oxidised LDL was not higher after the herring diet than after
      the reference diet. To conclude, a 6-week herring-rich diet significantly raised
      HDL compared with a diet of matched lean pork and chicken dishes. No adverse
      effects on in vivo oxidation or serum antioxidants were found after herring
      intake.

PMID- 18634707
TI  - Influence of a combination of Lactobacillus acidophilus NCFM and lactitol on
      healthy elderly: intestinal and immune parameters.
AB  - With increasing age, a number of physiological changes take place which are
      reflected in immune and bowel function. These changes may relate to the commonly
      assumed age-related changes in intestinal microbiota; most noticeably a reduction
      in bifidobacteria. The current study aimed at modifying the intestinal microbiota
      with a potential synbiotic on selected immune and microbiota markers. Healthy
      elderly subjects were randomised to consume during 2 weeks either a placebo
      (sucrose) or a combination of lactitol and Lactobacillus acidophilus NCFM twice
      daily in a double-blind parallel trial. After the intervention, stool frequency
      was higher in the synbiotic group than in the placebo group and a significant
      increase in faecal L. acidophilus NCFM levels was observed in the synbiotic
      group, after baseline correction. In contrast to the generally held opinion, the
      study subjects had faecal Bifidobacterium levels that were similar to those
      reported in healthy young adults. These levels were, nevertheless, significantly
      increased by the intervention. Levels of SCFA were not changed significantly. Of
      the measured immune markers, PGE2 levels were different between treatments and
      IgA levels changed over time. These changes were modest which may relate to the
      fact that the volunteers were healthy. Spermidine levels changed over time which
      may suggest an improved mucosal integrity and intestinal motility. The results
      suggest that consumption of lactitol combined with L. acidophilus NCFM twice
      daily may improve some markers of the intestinal microbiota composition and
      mucosal functions.

PMID- 18634708
TI  - Cut-off points for anthropometric indices of adiposity: differential
      classification in a large population of young women.
AB  - Anthropometric indices of adiposity include BMI, waist circumference and
      waist:height ratio. In the recruitment phase of a prospective cohort study
      carried out between 1998 and 2002 we studied a population sample of 11 786 white
      Caucasian non-pregnant women in Southampton, UK aged 20-34 years, and explored
      the extent to which proposed cut-off points for the three indices identified the
      same or different women and how these indices related to adiposity. Height,
      weight and waist circumference were measured and fat mass was estimated from
      skinfold thicknesses; fat mass index was calculated as fat mass/height1.65. Of
      the subjects, 4869 (42 %) women were overweight (BMI > or = 25 kg/m2) and 1849
      (16 %) were obese (BMI > or = 30 kg/m2). A total of 890 (8 %) subjects were not
      overweight but had a waist circumference > or = 80 cm and 748 (6 %) subjects were
      overweight but had a waist circumference < 80 cm (6 %). Of the women, 50 % had a
      BMI > or = 25 kg/m2 or a waist circumference > or = 80 cm or a waist:height ratio
      > or = 0.5. Of the variation in fat mass index, 85 % was explained by BMI, 76 %
      by waist circumference and 75 % by waist:height ratio. Our findings demonstrate
      that many women are differentially classified depending on which index of
      adiposity is used. As each index captures different aspects of size in terms of
      adiposity, there is the need to determine how the three indices relate to
      function and how they can be of use in defining risk of ill health in women.

PMID- 18634709
TI  - Antioxidant capacity, polyphenol content and iron bioavailability from algae
      (Ulva sp., Sargassum sp. and Porphyra sp.) in human subjects.
AB  - Marine algae are easily produced and are good sources of Fe. If this Fe is
      bioavailable, algae consumption could help to combat Fe deficiency and anaemia
      worldwide. The objective of the present study was to evaluate Fe bioavailability,
      polyphenol content and antioxidant capacity from three species of marine algae
      distributed worldwide. A total of eighty-three subjects received maize- or wheat
      based meals containing marine algae (Ulva sp., Sargassum sp. and Porphyra sp.) in
      different proportions (2.5, 5.0 and 7.5 g) added to the water to prepare the
      dough. All meals administered contained radioactive Fe. Absorption was evaluated
      calculating radioactive Fe incorporation in subjects' blood. The three species of
      marine algae were analysed for polyphenol content and reducing power. Algae
      significantly increased Fe absorption in maize- or wheat-based meals, especially
      Sargassum sp., due to its high Fe content. Increases in absorption were dose
      dependent and higher in wheat- than in maize-based meals. Total polyphenol
      content was 10.84, 18.43 and 80.39 gallic acid equivalents/g for Ulva sp.,
      Porphyra sp. and Sargassum sp., respectively. The antioxidant capacity was also
      significantly higher in Sargassum sp. compared with the other two species
      analysed. Ulva sp., Sargassum sp. and Porphyra sp. are good sources of
      bioavailable Fe. Sargassum sp. resulted in the highest Fe intake due to its high
      Fe content, and a bread containing 7.5 g Sargassum sp. covers daily Fe needs. The
      high polyphenol content found in Sargassum sp. could be partly responsible for
      the antioxidant power reported here, and apparently did not affect Fe absorption.

PMID- 18634710
TI  - Normal limits for heart rate as established using 24-hour ambulatory
      electrocardiography in children and adolescents.
AB  - BACKGROUND: To the best of our knowledge, normal limits of heart rate with
      respect to gender, and as established using 24-hour ambulatory Holter
      electrocardiography, have yet to be published for the entire age range of
      children and adolescents. OBJECTIVES: To establish the normal limits for heart
      rate in newborns, infants, children, and adolescents of both genders. PATIENTS
      AND METHODS: We obtained 24-hour Holter recordings from 616 healthy subjects aged
      from birth to 20 years with structurally normal hearts. The subjects were not
      receiving medication, and had not been submitted to prior cardiac intervention.
      Off-line analysis was performed with Mars 8000 scanners, analysing 5 consecutive
      RR intervals by the software available for automatic calculation of heart rate.
      All subjects were in sinus rhythm. Best-fit non-linear regressions were applied
      to correlate age and gender with minimum and mean heart rate, as well as with
      maximal RR-interval, and to calculate the 5th, 25th, 75th and 95th percentiles.
      RESULTS: We observed significant gender-dependent differences in heart rate for
      persons aged 10 years and older, with the males exhibiting lower minimal and mean
      heart rates, and higher RR-intervals, than the females. Correlation of heart rate
      with age and gender could be established with sufficient accuracy using non
      linear regression (p less than 0.0001): Minimum heart rate (male: R(2)=0.778,
      female: R(2) = 0.664) and mean heart rate (male: R(2) = 0.820, female: R(2) =
      0.736) decreased with age, while the maximal RR-interval prolonged (male: R(2) =
      0.562, female: R(2) = 0.486). Age and gender-related graphs of centiles were
      constructed. CONCLUSIONS: Heart rate, as documented using Holter recodings, can
      be correlated with age and gender, permitting establishments of normal gender
      specific limits for children and adolescents.

PMID- 18634711
TI  - Educational needs in adults with congenitally malformed hearts.
AB  - BACKGROUND AND AIM: The number of adults with congenitally malformed hearts is
      growing, and there is an increasing demand for their continuous follow-up. At
      present, different programmes have been established for adults with congenital
      cardiac disease, but there is a lack of knowledge regarding how education and
      psychosocial support should be given to achieve effects. Before developing
      educational programmes, it is necessary to be aware of the perspective of the
      patients. The aim of our study, therefore, was to describe how adults with
      congenitally malformed hearts experience their educational needs. METHODS: The
      study had a qualitative design. We interviewed 16 adults, aged from 19 to 55
      years, with congenitally malformed hearts. RESULTS: Two-way communication emerged
      as crucial to individualising education. Without good communication, those with
      congenitally malformed hearts, receiving information from providers of
      healthcare, are unable to transfer the information received. Thus, individualised
      education gives access to knowledge and the tools required to manage important
      areas in life, such as the congenital cardiac malformation, physical activity,
      the situation of life, treatment, and resources available for healthcare. The
      information given should provide easy access to knowledge through proper
      educational materials and methods, and be given with respect for the individual.
      This is facilitated if the education is tailored to the requirements of the
      individual in a holistic approach, and is provided through good communication.
      CONCLUSION: Our investigation shows that a structured educational programme needs
      to start from the perspective of the individual patient, and that two-way
      communication needs to be taken into consideration to enhance knowledge.

PMID- 18634712
TI  - Pitfalls of echocardiographic evaluation of anomalous origin of the left coronary
      artery from the pulmonary trunk.

PMID- 18634713
TI  - Looking beyond the biophysical realm to optimize health: results of a survey of
      psychological well-being in adults with congenital cardiac disease.
AB  - BACKGROUND: The purpose was to examine the relationship between the complexity of
      structural heart disease and psychological well-being in adults with congenital
      cardiac disease. METHODS: A total of 380 patients registered at the Adult
      Congenital Heart Clinic in Calgary, Alberta, Canada were surveyed. The patients
      were mailed a socio-demographic questionnaire and an instrument to measure
      psychological well-being. The instrument of psychological well-being measures six
      dimensions: positive relations with others, autonomy, environmental mastery,
      personal growth, purpose in life, and self-acceptance. Of the 380 patients
      surveyed, 85 of 205 patients with simple structural malformation responded,
      giving a response rate of 41%, and 78 of 175 patients with complex malformations,
      thus giving a response of 45%. RESULTS: There was no statistically significant
      difference in the mean scores of each of the six dimensions of psychological well
      being between those patients with simple and complex malformations. Two-way
      analysis of variance, and multivariate analysis of variance, found significant
      differences in mean scores for dimensions when other socio-demographic variables
      were included in the analysis. For example, significantly higher mean scores for
      the dimension of purpose in life was found in patients who obtained a higher
      level of education (p = 0.009), and in patients who were employed (p < 0.001). We
      present the socio-demographic variables that statistically impact the mean scores
      for the dimension of psychological well-being. CONCLUSION: Psychological well
      being is not affected by the complexity of the structural congenital cardiac
      disease. Certain socio-demographic variables that impact psychological well
      being, nonetheless, must be considered when developing multidisciplinary
      programmes to care for young adults with congenitally malformed hearts.

PMID- 18634714
TI  - Mid-term results following surgical treatment of congenital cardiac malformations
      in adults.
AB  - The long term consequences of untreated of residual or recurrent lesions pose
      unique challenges in the growing population of adults with congenitally malformed
      hearts. In our unit, 335 patients aged from 18 to 72 years, with a mean age of 35
      plus or minus 14 years, presented for correction of congenital cardiac disease
      from September, 1997, through December, 2006. Of the group, 42 (12.5%) had
      undergone one or more prior surgical procedures, 3 were admitted as emergencies,
      and a further 10 (3%) had suffered prior cardiac related complications. Symptoms
      had been noted by 181 patients (54%), and 42 (12.5%) had an established
      arrhythmia. Chromosomal anomalies were identified in 13 (3.8%), and diagnostic
      catheterisation was required in 201 (60%) patients. Of the overall group, 2
      patients died early (0.6%). Complications occurred in 61 patients (18%),
      including atrial fibrillation, pneumothorax, postoperative haemorrhage,
      pericardial or pleural effusions requiring drainage, stroke, complete heart
      block, endocarditis, wound dehiscence, and peripheral neuropathy. The median
      length of stay in the intensive care unit and hospital were 2 and 7 days,
      respectively. Death occurred later in 2 further patients (0.6%), due to atrial
      fibrillation and pulmonary hypertension. At mean follow-up of 63 plus or minus 30
      months, the majority of the remaining patients are well with resolution or
      significant improvement in their symptoms. Despite the long term deleterious
      effects of untreated, residual or recurrent congenital cardiac lesions in adults,
      therefore, we conclude that surgical correction can be achieved with low
      mortality and acceptable morbidity. Most significant complications are related to
      arrhythmias.

PMID- 18634715
TI  - Quantification of collateral aortopulmonary flow in patients subsequent to
      construction of bidirectional cavopulmonary shunts.
AB  - OBJECTIVES: We sought to provide a new method for quantifying collateral
      aortopulmonary flow in patients subsequent to construction of a bidirectional
      cavopulmonary shunt, and to clarify the clinical advantages of the new method.
      METHODS: We performed lung perfusion scintigraphy and cardiac catheterization in
      10 patients subsequent to construction of a bidirectional cavopulmonary shunt.
      First, the ratio of collateral to systemic flow was determined by whole-body
      images of lung perfusion scintigraphy, dividing the total lung count by the total
      body count minus the total lung count. Second, we integrated lung perfusion
      scintigraphy and cardiac catheterization data using a formula derived from the
      Fick principle, taking the ratio of pulmonary to systemic flow to be 1 plus the
      ratio calculated above and multiplied by the systemic saturation minus the
      inferior caval venous saturation divided by the pulmonary venous saturation minus
      the inferior caval venous saturation. Finally, the amount of collateral flow was
      obtained from the ratio of pulmonary to systemic flow. We evaluated the impact of
      collateral flow on the calculation of pulmonary vascular resistance. RESULTS: The
      median age at bidirectional cavopulmonary shunt was 1.41 years, and the median
      age at catheterization was 2.33 years. The mean amount of collateral flow was
      1.75 +/- 0.46 litres/min/m(2). The pulmonary vascular resistance calculated
      without considering the collateral flow was overestimated by an average of 57 +/-
      23%, compared to the resistance calculated with our new method. CONCLUSIONS: The
      use of scintigraphy combined with catheterization allows accurate determination
      of aortopulmonary collateral flow, and avoids overestimation of pulmonary
      vascular resistance in these candidates for the Fontan circulation.

PMID- 18634716
TI  - Four cases of acute flaccid paralysis associated with chikungunya virus
      infection.
AB  - The recent epidemic of chikungunya fever (2005-2006) in India has affected
      millions of people. The Andaman and Nicobar Islands, an archipelago situated in
      the Bay of Bengal 1200 km from peninsular India, also witnessed an outbreak of
      chikungunya fever starting in July 2006 which affected thousands of people.
      Chikungunya fever classically manifests as high fever, myalgia, arthralgia and
      arthritis and in a certain percentage of cases with maculopapular rashes.
      However, deviation from the classical clinical features of chikungunya fever was
      reported in the earlier and recent epidemics. During the recent epidemic in the
      Andaman and Nicobar Islands we came across ten cases of flaccid limb weakness
      following symptoms and signs suggestive of chikungunya fever. In four subjects we
      confirmed the diagnosis of chikungunya virus infection by serological method (IgM
      ELISA method). This is the case report of those four subjects.

PMID- 18634717
TI  - Comparison of the effects of a high- and normal-casein breakfast on satiety,
      'satiety' hormones, plasma amino acids and subsequent energy intake.
AB  - The present study compared the effects of a high- and normal-casein-protein
      breakfast on satiety, 'satiety' hormones, plasma amino acid responses and
      subsequent energy intake. Twenty-five healthy subjects (BMI 23.9 (SEM 0.3) kg/m2;
      age 22 (SEM 1) years) received a subject-specific standardised breakfast (20% of
      daily energy requirements): a custard with casein as the single protein source
      with either 10, 55 and 35 (normal-casein breakfast) or 25, 55 and 20 (high-casein
      breakfast) % of energy (En%) from protein, carbohydrate and fat respectively in a
      randomised, single-blind design. Appetite profile (visual analogue scale; VAS),
      plasma glucose, insulin, glucagon-like peptide 1, ghrelin and amino acid
      concentrations were determined for 4 h; here the sensitive moment in time for
      lunch was determined. Subjects came for a second set of experiments and received
      the same custards for breakfast, and an ad libitum lunch was offered at 180 min
      after breakfast; energy intake was assessed. There were increased scores of
      fullness and satiety after the 25 En% casein-custard compared with the 10 En%
      casein-custard, particularly at 180 min (26 (SEM 4) v. 11 (SEM 5) mm VAS; P<0.01)
      and 240 min (13 (SEM 5) v. -1 (SEM 5) mm VAS; P<0.01). This coincided with
      prolonged elevated plasma amino acid concentrations; total amino acids and
      branched-chain amino acids were higher after the 25 En% casein-custard compared
      with the 10 En% casein-custard at 180 and 240 min (P<0.001). There was no
      difference in energy intake (3080 (SEM 229) v. 3133 (SEM 226) kJ for 25 En% and
      10 En% respectively; NS) from the ad libitum lunch. In conclusion, a breakfast
      with 25% of energy from casein is rated as being more satiating than a breakfast
      with 10% of energy from casein at 3 and 4 h after breakfast, coinciding with
      prolonged elevated concentrations of plasma amino acids, but does not reduce
      subsequent energy intake.

PMID- 18634719
TI  - Early syphilis: a cause of mono-arthritis of the knee.
AB  - The number of syphilis cases has increased in the UK in recent years, but many
      clinicians have limited experience in the diagnosis and treatment of this
      disease. If early diagnosis is not made and treated promptly with antibiotics,
      the disease may remain latent until the more serious manifestations of tertiary
      syphilis develop. We present the case of a 27-year-old man who presented with an
      acute mono-arthritis secondary to syphilis. The condition responded to antibiotic
      therapy. Orthopaedic surgeons should be aware of the diagnosis and consider it in
      patients with an acute arthropathy.

PMID- 18634718
TI  - The maintained discharge of rat retinal ganglion cells.
AB  - Action potentials were recorded from rat retinal ganglion cell fibers in the
      presence of a uniform field, and the maintained discharge pattern was
      characterized. Spike trains recorded under ketaminexylazine. The majority of
      cells had multimodal interval distributions, with the first peak in the range of
      25.00.97). Both ON and OFF cells show serial correlations between adjacent
      interspike intervals, while ON cells also showed second-order correlations. Cells
      with multimodal interval distribution showed a strong peak at high frequencies in
      the power spectra in the range of 28.9-41.4 Hz. Oscillations were present under
      both anesthetic conditions and persisted in the dark at a slightly lower
      frequency, implying that the oscillations are generated independent of any light
      stimulus but can be modulated by light level. The oscillation frequency varied
      slightly between cells of the same type and in the same eye, suggesting that
      multiple oscillatory generating mechanisms exist within the retina. Cells with
      high-frequency oscillations were described well by an integrate-and-fire model
      with the input consisting of Gaussian noise plus a sinusoid where the phase was
      jittered randomly to account for the bandwidth present in the oscillations.

PMID- 18634720
TI  - Presentation and management of perirectal sepsis.
AB  - Perirectal sepsis is a potentially severe complication which may follow minor
      anorectal intervention and be slow to be diagnosed and treated. We report the
      presentation and outcome of three patients with perirectal sepsis of differing
      aetiologies. Awareness of the possible diagnosis, urgent investigation with cross
      sectional imaging and immediate treatment with broad-spectrum antibiotics is
      vital. However, radical surgical intervention may be necessary. This report
      highlights the importance of investigating patients with persistent pelvic pain
      after minor anorectal procedures or trauma and maintaining a high index of
      suspicion for this important complication.

PMID- 18634721
TI  - Kidney salvage using the fibrinogen- and thrombin-coated sponge TachoSil during
      nephron-sparing surgery for the resection of large renal tumours.
AB  - Nephron-sparing surgery can permit functional preservation of the kidney in
      carefully selected patients. We report nephron-sparing surgery in two patients
      with renal tumours > or = 5 cm. Both patients were successfully treated, with
      kidney salvage facilitated through the use of the fibrinogen- and thrombin-coated
      collagen sponge, TachoSil (Nycomed UK Ltd, UK).

PMID- 18634722
TI  - True trilineage haematopoiesis in excised heterotopic ossification from a
      laparotomy scar: report of a case and literature review.
AB  - We report a case of true trilineage haematopoiesis in an excised area of
      heterotopic ossification from an upper mid-line laparotomy scar. Heterotopic
      ossification is a rare complication of abdominal surgery and usually occurs when
      upper mid-line incisions are utilised. Whereas cases of heterotopic ossification
      in abdominal incisions are not exceedingly rare, true trilineage haematopoiesis
      in such an area of heterotopic ossification, to our knowledge, has only been
      previously reported once in the English literature.

PMID- 18634723
TI  - Angiosarcoma in an area of lipodermatosclerosis.
AB  - We present an unusual case in a post phlebitic lower limb that had previously
      developed an area of lipodermatosclerosis. An area within this broke down as a
      result of an angiosarcoma rather than the more probable: formation of a venous
      ulcer.

PMID- 18634724
TI  - Diagnostic dilemma of adrenal enlargement after acute pancreatitis.
AB  - A case is presented illustrating the diagnostic dilemma of adrenal enlargement
      following acute pancreatitis.

PMID- 18634726
TI  - The elusive electromyogram in the overactive bladder: a spark of understanding.
AB  - It has been said that a technique capable of recording a urinary bladder
      electromyogram could be useful in the clinical evaluation of the detrusor
      neuropathies and myopathies implicated in the generation of lower urinary tract
      symptoms. However, in contrast to electromyography of skeletal and cardiac
      muscle, detrusor smooth muscle electromyography has remained in its infancy
      despite 50 years of scientific effort. The principal problems appear to be
      isolation of the real signal from artefacts, and the doubtful existence of
      electromyographic activity during cholinergic muscle contraction. The discovery
      of purinergic neuromuscular transmission in the overactive human bladder has
      renewed interest in detrusor electromyography as, in contrast to cholinergic
      mechanisms, purinergic mechanisms can generate extracellular electrical activity.
      In this paper, the development and validation of a novel technique for recording
      electrical activity from neurologically intact guinea-pig and human detrusor in
      vitro is described. A purinergic electromyographic signal is characterised and it
      is shown that detrusor taken from overactive human bladders has a greater
      propensity to generate electromyographic activity than normal by virtue of an
      aberrant purinergic mechanism.

PMID- 18634727
TI  - Pancreas transplantation.
AB  - Over the last 5 years, there has been a resumed interest in treating diabetes by
      transplantation, particularly islet transplantation. However, despite advances
      being reported in Canada and the US, replication in the UK has been much more
      difficult. At present there is still only one treatment that can consistently
      reverse insulin independence in the long-term and that is whole pancreas
      transplantation. Long-term normoglycaemia has beneficial effects on preventing
      and ameliorating the secondary complications of diabetes and will be discussed.

PMID- 18634729
TI  - Sinus excision, release of coccycutaneous attachments and dermal-subcuticular
      closure (XRD procedure): a novel technique in flattening the natal cleft in
      pilonidal sinus treatment.
AB  - INTRODUCTION: The objective of this study was to analyse, prospectively, the
      outcome of a new technique - excision of pilonidal sinus and flattening the natal
      cleft by division of the coccycutaneous attachments at the lower end of the
      incision. PATIENTS AND METHODS: Sixty-six consecutive patients with chronic
      pilonidal sinuses were treated between 1995 and 2001. The procedure consisted of
      an elliptical, wide, local excision, release of the coccycutaneous attachments
      and primary closure using dermal-subcuticular closure (XRD). Suction drains were
      used until drainage was minimal. The height of skin level at the lower angle of
      the wound from the coccyx was measured intra-operatively before and after
      division of the coccycutaneous attachments. Postoperatively, patients were
      assessed for hospital stay, return to normal activity, complications and
      recurrence. RESULTS: Sixty-four patients (97%) were males, median age 27 years.
      The height of skin level rose from a mean of 1.8 cm (95% CI, 1.78-1.85) to a mean
      of 3.8 cm (95% CI, 3.77-3.88; P < 0.001). Morbidity affected 12 patients (18%),
      epidermal separation of the lower wound angles (6 patients), seromas (5 patients)
      and 1 wound dehiscence at 2 weeks. All other wounds healed primarily without
      dehiscence. There were no recurrences after a median follow-up of 22.5 months
      (range, 12-38 months). CONCLUSIONS: Release of the coccycutaneous attachments is
      an easy technique to learn, which seems to be an effective way of flattening the
      natal cleft and may result in lower recurrence rate. This technique should be
      tried in uncomplicated pilonidal sinus disease before more complex procedures are
      attempted.

PMID- 18634730
TI  - Non-attendance at the colorectal clinic: a prospective audit.
AB  - INTRODUCTION: Non-attendance in the out-patient department has financial costs
      for the NHS and clinical implications to the non-attender and those awaiting an
      appointment. The aim of this audit was to quantify the percentage of non
      attenders at colorectal clinics in a UK teaching hospital, assess which factors
      affected attendance, establish why individuals fail to attend and to implement
      appropriate change. PATIENTS AND METHODS: The number of 'did-not-attend' patients
      was recorded initially for 686 appointments. Non-attenders were contacted by post
      or telephone to ask why this was so. The study was then repeated following
      telephone reminders to 391 patients due to attend clinic. The 'did-not-attend'
      rates in the two limbs of the completed audit cycle were then compared. RESULTS:
      The initial study revealed a 'did-not-attend' rate of 21%, with significantly
      more males than females failing to attend (males, 28.6%; females, 16.9%; P =
      0.001). The 'did-not-attend' rate was not significantly affected by the day of
      the week, time of appointment or by the weather. There were 51.7% responses to
      either the postal or telephone questionnaire regarding non-attendance. Of these,
      27.7% did not receive an appointment letter or received it after the appointment.
      Hospital administration problems were cited as accounting for 34.2% of 'did-not
      attends'. In the post-intervention limb, 87 patients (22%) replied to the
      reminder telephone call, of whom 9 (10%) cancelled their appointment and 78 (90%)
      confirmed that they would attend. The 'did-not-attend' rate fell to 19.7%
      although this was not a significant reduction. CONCLUSIONS: Telephoning patients
      before their appointments is labour intensive and did not significantly improve
      the 'did-not-attend' rate. Although hospital administration errors account for a
      significant number of the 'did-not-attends', patients also have a responsibility
      to notify the hospital if they are unable to attend.

PMID- 18634731
TI  - Does limiting long-term follow-up for breast cancer allow all referrals to be
      seen in 2 weeks?
AB  - INTRODUCTION: The UK National Institute for Health and Clinical Excellence (NICE)
      recommends that breast cancer follow-up should be limited to 2-3 years stating
      this will 'release resources' making it 'possible for all women with breast
      symptoms to be seen within 2 weeks'. In 2000, breast cancer follow-up services in
      North Bristol were redesigned to reflect evidence-based best practice. The aim of
      this paper is to assess the impact of this policy on numbers of follow-ups,
      clinic capacity and waiting times. PATIENTS AND METHODS: Data regarding the
      numbers of new and follow-up patients seen in breast clinic between January 2000
      and December 2005 were collected from the hospital Patient Administration System.
      New patients were categorised as either 'routine' or 'urgent' according to '2
      week wait' rule guidelines. Median waiting times were calculated for each group
      and nominal appointment times assigned in an attempt to assess the effect of any
      changes on clinic capacity. RESULTS: The number of follow-ups decreased by 33% as
      a result of the new policy. Numbers of referrals over the same period, however,
      increased by 14%. Routine referrals declined, but there was a 27% increase in '2
      week wait' patients. Waiting times for routine appointments initially decreased
      in response to reduced follow-up, but then rose as the number of '2-week wait'
      referrals increased. CONCLUSIONS: Reducing long-term follow-up is a simple and
      effective method of increasing clinic capacity but its effects are inadequate and
      transient in the face of increasing service demand. Additional innovative and
      creative strategies will be required if all breast patients are to be seen within
      2 weeks.

PMID- 18634733
TI  - Prevalence of abdominal aortic aneurysms in over 65-year-old men with inguinal
      hernias.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of abdominal
      aortic aneurysms (AAAs) in over 65-year-old men who have inguinal hernias and
      discuss if pre-operative selective screening of this population is appropriate.
      PATIENTS AND METHODS: A prospective study on 70 consecutive male patients with an
      age range of 65-88 years (mean, 74 years) who were referred to a single vascular
      consultant's out-patient clinic with an inguinal hernia were screened for the
      presence of an AAA with an ultrasound scan before hernia repair over a period of
      3 years. RESULTS: Two patients were found to have an AAA measuring 3.8 cm and 6.0
      cm giving an AAA prevalence of 3% (exact 95% confidence interval = 0-10%).
      CONCLUSIONS: This study does not demonstrate an increased AAA prevalence in over
      65-year-old male patients with inguinal hernias, scanned pre-operatively when
      compared to screening programmes. Selective screening of this cohort cannot be
      justified on this evidence.

PMID- 18634734
TI  - Are periods of low atmospheric pressure associated with an increased risk of
      abdominal aortic aneurysm rupture?
AB  - INTRODUCTION: Seasonal variation in rates of abdominal aortic aneurysm (AAA)
      rupture has previously been described. However, only two studies, to date, have
      suggested that periods of low atmospheric pressure may account for this
      observation and both returned apparently contradictory findings. The objective of
      this study was to demonstrate whether periods of low atmospheric pressure are
      indeed associated with an increased likelihood of AAA rupture presentation.
      PATIENTS AND METHODS: A total of 182 cases of ruptured AAA were identified
      retrospectively from two centres over a 6-year period from January 2000 to
      December 2005. Local meteorological data for the corresponding period was
      obtained from the UK Meteorological Office which was recorded daily at a local
      weather station. Statistical analysis using Student's t-test, ANOVA (Kruskal
      Wallis), linear regression and multiple logistic regression was conducted to
      identify significant relationships from the data. RESULTS: Days of rupture
      presentation were associated with a significantly lower daily mean atmospheric
      pressure when compared with days when no rupture occurred (P = 0.025). Multiple
      logistic regression demonstrated a significant association between low daily
      atmospheric pressure and rupture incidence (P = 0.033) which appeared to be
      independent of temperature. A significant seasonal trough in atmospheric pressure
      was observed in October and November (Kruskal-Wallis, P < 0.001); however, there
      was no corresponding autumnal peak in rupture incidence (P = 0.232). CONCLUSIONS:
      The findings of this study appear to confirm the assertion that low atmospheric
      pressure is associated with an increased risk of AAA rupture on a day-to-day
      basis; however, no evidence was identified to support a change in policy
      regarding prioritising elective surgery based on seasonal risk.

PMID- 18634735
TI  - Removing symptomatic gallstones at their first emergency presentation.
AB  - INTRODUCTION: Early operations for symptomatic gallstones are gaining favour as
      the complication rate is thought to be lower and it reduces the overall
      morbidity. This study was performed to clarify how frequently early operations
      were being performed and what benefits resulted. PATIENTS AND METHODS: Case notes
      of 171 patients who underwent laparoscopic cholecystectomy at Princess Alexandra
      Hospital Harlow were retrospectively reviewed. They were grouped according to
      their initial diagnosis (cholelithiasis, acute cholecystitis) and the delay to
      surgery (early, interval). Forty-one cases were excluded as they either had
      incomplete notes or the initial diagnosis was a different manifestation of
      gallstones such as pancreatitis. Those receiving interval operations were then
      grouped according to the mode of their initial presentation. A total of 130 case
      notes were analysed. RESULTS: The delay for an interval operation was 3-6 months
      compared with less than 2 weeks for early operations. Of patients with acute
      cholecystitis, 43% had early operations but only 12% of patients with
      cholelithiasis. Waiting for interval operations was associated with multiple re
      admissions equivalent to an average of one extra presentation to accident and
      emergency per patient. This was particularly marked if the initial presentation
      was to accident and emergency rather than outpatients (P = 0.003). Complication
      rates were also higher in the interval group. CONCLUSIONS: Early cholecystectomy
      on the next available list is likely to reduce morbidity and the long-term in
      patient burden so should be recommended for all patients presenting as an
      emergency with symptomatic gallstones.

PMID- 18634736
TI  - Perception of abnormal serum prostate-specific antigen (PSA) test results amongst
      family practitioners.
AB  - INTRODUCTION: With increased use of serum prostate-specific antigen (PSA)
      testing, prostate cancers are diagnosed at an earlier stage in younger men, when
      radical curative treatments are appropriate. Modifications of the PSA test such
      as PSA velocity and age-adjusted values are available to aid in the selection of
      patients for biopsy. However, it is not clear whether these data are used in
      general practice. PATIENTS AND METHODS: A self-administered questionnaire was
      mailed to all primary care practices within one region in the UK. A series of
      visual analogue questions designed to identify referral thresholds for age
      adjusted PSA levels and PSA velocity were used to identify patterns in referral
      behaviour. RESULTS: Individual family practitioners see only small numbers of
      patients requesting PSA tests or with newly diagnosed prostate cancer each year.
      The median (range) thresholds considered for referral at ages 45, 55, 65, 75 and
      85 years were 4.5 ng/ml (2.5-15.5 ng/ml), 5.5 ng/ml (3.0-15.5 ng/ml), 6.5 ng/ml
      (3.5-15.5 ng/ml), 6.5 ng/ml (3.5-25.5 ng/ml), and 7.5 ng/ml (3.5-25.5 ng/ml),
      respectively. Only 5% of practitioners correctly identified the age-specific PSA
      threshold for referral of a 45-year-old man. CONCLUSIONS: It is important to
      remember that younger men (even those in their forties and fifties) may be at
      risk of prostate cancer even if asymptomatic. It is important in a climate of
      increasing demand for PSA testing that those who initiate the process understand
      the implications and limitations of testing, including appropriate triggers for
      referral to secondary care. The exact approach required for the successful
      dissemination of this information to primary care is not clear, but our data
      suggest that a better understanding is required.

PMID- 18634737
TI  - Redefining urological history taking - anal intercourse as the cause of
      unexplained symptoms in heterosexuals.
AB  - INTRODUCTION: Symptoms suggestive of genito-urinary infection are frequent
      reasons for visits to general practitioners and account for approximately 15% of
      referrals to out-patient urology. The symptoms may be non-specific, and patients
      can undergo multiple investigations in an attempt to identify a cause. PATIENTS
      AND METHODS: We have seen several such patients, all of whom had engaged in
      unprotected heterosexual anal intercourse prior to the onset of their symptoms.
      Presenting complaints included urethral discomfort, acute epididymitis resistant
      to standard antibiotics, and sudden onset of overactive bladder symptoms.
      RESULTS: These patients illustrate the importance of careful history taking.
      Whilst some questions may be difficult to ask, they may reveal precipitating
      factors that the patient will be reluctant to volunteer. The repetitive nature of
      the behaviour may explain the chronicity of symptoms experienced by the patients,
      and avoidance of this activity may be the only management needed to improve them.
      For those with infective symptoms, the clinician's choice of antibiotic can be
      altered to provide anaerobic cover. CONCLUSIONS: A history of anal intercourse
      should be sought in patients with unexplained genito-urinary symptoms.

PMID- 18634739
TI  - The benefit of modified rehabilitation and minimally invasive techniques in total
      hip replacement.
AB  - INTRODUCTION: We wished to assess if an intensive rehabilitation regimen alone,
      or one combined with modified anaesthetic and surgical techniques, can change the
      speed of rehabilitation or the length of hospital stay after total hip
      replacement. PATIENTS AND METHODS: We compared 44 patients who had followed a
      traditional care pathway, with 38 patients who had rehabilitated under a new
      rehabilitation protocol, with 40 patients who had also received modified,
      minimally invasive techniques. The speed of rehabilitation was measured in terms
      of three specific milestones accomplished on the day after surgery. RESULTS: We
      found a statistically significant improvement in the day after surgery each
      activity was possible. The length of hospital stay was reduced from 6.5 days to
      5.4 days to 4.1 days, a difference which was also statistically significant.
      CONCLUSIONS: The data support the view that a new rehabilitation protocol alone
      can reduce the length of hospital stay and hasten rehabilitation. The combination
      of modified anaesthetic and minimally invasive surgical techniques with the new
      rehabilitation regimen can further improve short-term outcome after total hip
      replacement.

PMID- 18634740
TI  - Adherence to recommendations designed to decrease intra-operative wound
      contamination.
AB  - INTRODUCTION: The incidence of wound infection following total hip and knee
      arthroplasty has fallen with the introduction of laminar vertical laminar
      airflow, occlusive clothing and prophylactic antibiotics. However, infection
      still occurs after prosthetic joint replacement and can have devastating
      consequences. Intra-operative wound contamination is the major source of
      infection. Measures proven to decrease intra-operative wound contamination
      include chlorhexidine lavage, removal of jewellery, covering old jewellery, ears,
      nose, mouth and hair and wearing theatre clothing in an occlusive manner.
      PATIENTS AND METHODS: Posters explaining this practice were placed at eye level
      in the scrub area of orthopaedic theatres and adoption of these techniques was
      observed covertly before and after. RESULTS: Eighty-two personnel were audited
      before the poster was erected and 90 afterwards. Only 2 of 12 observed standards
      were adhered to 100% of the time. CONCLUSIONS: Education by posters did not
      significantly improve adherence to protocols. Compliance with protocols was worse
      amongst non-scrubbed theatre personnel.

PMID- 18634741
TI  - Investigating bacterial growth in surgical theatres: establishing the effect of
      laminar airflow on bacterial growth on plastic, metal and wood surfaces.
AB  - INTRODUCTION: Infection is a devastating complication of surgery. Intra-operative
      wound contamination is a common cause of infection. A number of measures have
      been effective in reducing wound contamination. One such measure is laminar flow.
      Controversy exists as to whether it is safe to keep open instruments and implants
      outside the laminar flow. This study compares bacterial contamination of wood,
      plastic and stainless steel within and outside the laminar flow. MATERIALS AND
      METHODS: Identically shaped and sized tiles were left for 90 min within and
      outside the laminar flow and then cultured for bacterial growth. RESULTS: A third
      of metal and plastic tiles were contaminated, but only 10% of wooden tiles,
      suggesting that wood is a more hostile environment for bacteria. There was no
      difference in contamination between tiles placed inside and those placed outside
      the laminar flow. CONCLUSIONS: This study suggests that placing instruments and
      implants outside the laminar flow is a safe practice.

PMID- 18634742
TI  - The 'parent's kiss': an effective way to remove paediatric nasal foreign bodies.
AB  - INTRODUCTION: The objectives of this study were to: (i) evaluate the
      effectiveness of 'parent's kiss' as a technique for removal of nasal foreign
      bodies in children; and (ii) determine whether this technique reduces the number
      of children requiring general anaesthesia for their removal. PATIENTS AND
      METHODS: This was a prospective observational study in the accident and emergency
      and ENT departments at Luton and Dunstable Hospital. The participants were 31
      children with nasal foreign bodies, under the age of 5 years, presenting via the
      acute services over a 6-month period. The primary outcome measured was successful
      removal of nasal foreign body with the 'parent's kiss' technique. Secondary
      outcome was reduction in the number of general anaesthetics following
      introduction of the technique. RESULTS: The technique was successful in 20 out of
      the 31 children (64.5%) in the study group. Only one patient required general
      anaesthesia for removal of nasal foreign body (3%). This compares with a rate of
      32.5% requiring removal under general anaesthetic in the preceding 6-month
      period. The 'parent's kiss', when not successful, seemed to improve the
      visibility of the foreign body making their subsequent removal easier.
      CONCLUSIONS: The 'parent's kiss' is an effective technique. It is non-traumatic,
      both physically and emotionally, for the child subjected to it. We advocate that
      it should be used routinely as a first line of management in children with a
      nasal foreign body in the primary care setting.

PMID- 18634743
TI  - Bilateral retrovascular femoral hernia.
AB  - A 34-year-old woman with cystic fibrosis presented with bilateral femoral
      hernias, which were found to be retrovascular at operation. The hernias were not
      amenable to conventional open or laparoscopic repair, and were repaired using pre
      peritoneal mesh inserted deep to transversalis fascia. The anatomical basis and
      management of uncommon variants of femoral hernia are discussed.

PMID- 18634744
TI  - NICE/NPSA patient safety pilot.

PMID- 18634745
TI  - Comment on: minimally invasive total hip arthroplasty.

PMID- 18634747
TI  - Direct determination of intracellular daunorubicin in intact confluent monolayers
      of AT1 prostate carcinoma cells using a multiwell-multilabel counter.
AB  - The cytostatic drug daunorubicin exerts its toxic action by intercalating into
      the DNA. The efficacy of daunorubicin depends on the intracellular amount in the
      tumor cell. Here we have evaluated the use of a multiwell-multilabel reader for
      the direct determination of the fluorescent cytostatic drug daunorubicin in a
      prostate carcinoma cell line (AT1 R-3327 Dunning prostate carcinoma cells) grown
      on 24-well plates. We present evidence that this simple fluorescent parameter is
      a good measure for the toxicologically relevant amount of the drug intercalated
      into the DNA and, therefore, is a good predictor for the drug's cytotoxicity. The
      amount of cationic cytostatics in a tumor cell is primarily a function of the
      efflux pump protein p-gycoprotein (pGP). Therefore, it is of great value that the
      assay is also suitable for the estimation of the multidrug resistance efflux pump
      (pGP) activity.

PMID- 18634748
TI  - Enzymatic analysis of uridine diphosphate N-acetyl-D-glucosamine.
AB  - The Methanococcus maripaludis MMP0352 protein belongs to an oxidoreductase family
      that has been proposed to catalyze the NAD(+)-dependent oxidation of the 3''
      position of uridine diphosphate N-acetyl-D-glucosamine (UDP-GlcNAc), forming a 3
      hexulose sugar nucleotide. The heterologously expressed MMP0352 protein was
      purified and shown to efficiently catalyze UDP-GlcNAc oxidation, forming one NADH
      equivalent. This enzyme was used to develop a fixed endpoint fluorometric method
      to analyze UDP-GlcNAc. The enzyme is highly specific for this acetamido sugar
      nucleotide, and the procedure had a detection limit of 0.2 microM UDP-GlcNAc in a
      1-ml sample. Using the method of standard addition, UDP-GlcNAc concentrations
      were measured in deproteinized extracts of Escherichia coli, Saccharomyces
      cerevisiae, and HeLa carcinoma cells. Equivalent concentrations were determined
      by both enzymatic and chromatographic analyses, validating this method. This
      procedure can be adapted for the high-throughput analysis of changes in cellular
      UDP-GlcNAc concentrations in time series experiments or inhibitor screens.

PMID- 18634749
TI  - Poliovirus 2b insertion into lipid monolayers and pore formation in vesicles
      modulated by anionic phospholipids.
AB  - Enterovirus 2B viroporin has been involved in membrane permeabilization processes
      occurring late during cell infection. Even though 2B lacks an obvious signal
      sequence for translocation, the presence of a Lys-based amphipathic domain
      suggests that this product bears the intrinsic capacity for partitioning into
      negatively charged cytofacial membrane surfaces. Pore formation by poliovirus 2B
      attached to a maltose-binding protein (MBP) has been indeed demonstrated in pure
      lipid vesicles, a fact supporting spontaneous insertion into and direct
      permeabilization of membranes. Here, biochemical evidence is presented indicating
      that both processes are modulated by phosphatidylinositol and phosphatidylserine,
      the main anionic phospholipids existing in membranes of target organelles.
      Insertion into lipid monolayers and partitioning into phospholipid bilayers were
      sustained by both phospholipids. However, MBP-2B inserted into phosphatidylserine
      bilayers did not promote membrane permeabilization and addition of this lipid
      inhibited the leakage observed in phosphatidylinositol vesicles. Mathematical
      modelling of pore formation in membranes containing increasing phosphatidylserine
      percentages was consistent with its inhibitory effect arising from a higher
      reversibility of MBP-2B surface aggregation. These results support that 2B
      insertion and pore-opening are mechanistically distinguishable events modulated
      by the target membrane anionic phospholipids.

PMID- 18634750
TI  - ATP-binding cassette transporters in Escherichia coli.
AB  - ATP-binding cassette (ABC) transporters are integral membrane proteins that
      actively transport molecules across cell membranes. In Escherichia coli they
      consist primarily of import systems that involve in addition to the ABC
      transporter itself a substrate binding protein and outer membrane receptors or
      porins, and a number of transporters with varied functions. Recent crystal
      structures of a number of ATPase domains, substrate binding proteins, and full
      length transporters have given new insight in the molecular basis of transport.
      Bioinformatics approaches allow an approximate identification of all ABC
      transporters in E. coli and their relation to other known transporters.
      Computational approaches involving modeling and simulation are beginning to yield
      insight into the dynamics of the transporters. We summarize the function of the
      known ABC transporters in E. coli and mechanistic insights from structural and
      computational studies.

PMID- 18634751
TI  - Identification of an Arabidopsis transmembrane bZIP transcription factor involved
      in the endoplasmic reticulum stress response.
AB  - Among 75 bZIP transcription factors identified in Arabidopsis, 3 (AtbZIP17,
      AtbZIP28, and AtbZIP49) possess a putative transmembrane domain (TMD) in addition
      to AtbZIP60, which was characterized previously. In the present study, cDNAs of
      AtbZIP17 and AtbZIP28 were isolated. Truncated forms of AtbZIP17 and AtbZIP28
      lacking the C-terminal domain including TMD were examined as putative active
      forms. One of them, AtbZIP28DeltaC, activated BiP1 and BiP3 promoters through the
      cis-elements P-UPRE and ERSE responsible for the ER stress response.
      Subsequently, a fusion protein of green fluorescent protein (GFP) and AtbZIP28
      was expressed in Arabidopsis cultured cells. Under non-stress conditions, GFP
      fluorescence localization almost overlapped with an ER marker; however,
      tunicamycin and dithiothreitol treatment clearly increased GFP fluorescence in
      the nucleus suggesting that the N-terminal fragment of AtbZIP28 translocates to
      the nucleus in response to ER stress.

PMID- 18634752
TI  - Comprehensive screening of amber suppressor tRNAs suitable for incorporation of
      non-natural amino acids in a cell-free translation system.
AB  - Incorporation of non-natural amino acids into proteins in response to amber or
      four-base codons is a useful technology for protein research. In the case of the
      amber codon, however, release factor 1 can competitively decode the same codon,
      and consequently inhibit the incorporation of non-natural amino acids. To improve
      amber codon-mediated incorporation, we carried out a comprehensive screening of
      amber suppressor tRNAs derived from all tRNAs encoded in the genomes of
      Escherichia coli K12 and Mycoplasma capricolum. The amber suppressor tRNAs were
      synthesized from synthetic genes, aminoacylated with a fluorescent non-natural
      amino acid, and added to an E. coli cell-free translation system. Fluorescent SDS
      PAGE analysis indicated that Trp tRNAs showed high suppressor activity in both
      organisms. Further mutagenesis and screening revealed that M. capricolum Trp(1)
      tRNA with G1C72A73 mutation is the most suitable for efficient and specific
      incorporation of non-natural amino acids into proteins in response to the amber
      codon.

PMID- 18634753
TI  - A novel series of vectors for chromosomal integration in fission yeast.
AB  - A series of fission yeast targeting vectors that can be used for wild-type
      strains having no selectable markers have been designed. The functions of one of
      three marker genes, lys1(+), arg1(+), and his3(+), involved in amino acid
      synthesis, are impaired by integration of the fragments generated by restriction
      enzyme digestion of the plasmids. Successful integration of the fragments into
      the targeted loci can be readily verified by their requirement for amino acids,
      or by the PCR diagnostic analysis. Since these selection markers are not used
      commonly in fission yeast, these plasmids are likely to facilitate studies that
      require the co-expression of genes such as co-localization and co
      immunoprecipitation experiments, by employing them in combination with most of
      the previously reported markers.

PMID- 18634754
TI  - Recombinant fibrinogenase from Agkistrodon acutus venom protects against sepsis
      via direct degradation of fibrin and TNF-alpha.
AB  - Severe sepsis remains a leading cause of death and disability because of less
      effective therapy available for this disease. A complex interplay between the
      inflammatory factors and the coagulation pathways seems to be the fundamental
      mechanisms for the pathogenesis of sepsis. Here we report that recombinant
      fibrinogenase II (rF II) from Agkistrodon acutus plasmin-independently degraded
      the thrombi, and inhibited inflammatory responses by direct and specific
      degradation of tumor necrosis factor alpha (TNF-alpha) induced by
      lipopolysaccharide (LPS) without showing proteolytic activities on interleukin-1
      (IL-1), cluster of differentiation 68 (CD68) and some other serum proteins. We
      also report that rF II effectively protected against LPS induced sepsis in a
      rabbit model. Administration of rF II reduced hepatic and renal damage, decreased
      the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and
      increased survival rate in LPS-induced sepsis rabbits. We further confirmed the
      rescue effect of rF II on severe sepsis in rat caecal ligation and puncture (CLP)
      model. Our findings suggest that rF II could effectively protect against sepsis
      via direct degradation of microthrombi and inflammatory factor TNF-alpha as well
      as provide a novel strategy to develop a single proteinase molecule for targeting
      the main pathological processes of this disease.

PMID- 18634755
TI  - Novel job opportunities in cell death!

PMID- 18634756
TI  - 5Alpha-dihydrotestosterone up-regulates transthyretin levels in mice and rat
      choroid plexus via an androgen receptor independent pathway.
AB  - Transthyretin (TTR) is a 55 kDa plasma homotetrameric protein mainly synthesized
      in the liver and choroid plexuses (CPs) of the brain that, functions as a carrier
      for thyroxin and retinol binding protein. It sequesters amyloid beta (Abeta)
      peptide, and TTR levels in the cerebrospinal fluid (CSF) appear to be inversely
      correlated with Alzheimer's disease (AD) onset and progression. Androgen
      deprivation increases plasma Abeta levels, which indicate that androgens may
      reduce the levels of soluble Abeta, the peptide widely implicated in the
      initiation of AD pathogenesis; however, the underlying mechanisms are still
      poorly understood. In this study we examined the effects of 5alpha
      dihydrotestosterone (DHT) on TTR protein and mRNA levels, in primary cultures of
      rat CPs epithelial cells (CPEC) by Western blot, and real time PCR, respectively.
      Moreover, TTR concentrations were measured in the CSF of castrated wild-type, and
      transgenic mice expressing human TTR subjected to DHT treatment, by
      radioimmunoassay and ELISA, respectively. TTR mRNA expression was also compared
      in the CPs, of the animals from each experimental group by real time PCR. DHT
      treatment increased TTR protein levels in CPEC, and induced TTR transcription in
      these cells. The combination of flutamide with DHT in the treatment of CPEC did
      not abrogate DHT-induced TTR levels, suggesting that TTR is up-regulated via an
      androgen receptor independent pathway. In the CPs of both mice strains, DHT also
      increased TTR mRNA levels, but no significant differences in TTR protein levels
      were detected in the CSF of these animals. These findings open a wide range of
      possibilities for future studies on Abeta deposition and cognitive function, in
      response to androgen induction of TTR in animal models of AD.

PMID- 18634757
TI  - Implantation of human umbilical cord-derived mesenchymal stem cells as a
      neuroprotective therapy for ischemic stroke in rats.
AB  - In the present study, we examined the neuroprotective effects and mechanisms of
      implanted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in
      ischemic stroke. hUC-MSCs were isolated from the endothelial/subendothelial
      layers of the human umbilical cord and cultured. Twenty days after the induction
      of in vitro neuronal differentiation, about 77.4% of the inoculated hUC-MSCs
      displayed morphological features of neurons and expressed neuronal cell markers
      like TU-20, Trk A, NeuN, and NF-M. However, functionally active neuronal type
      channels were not detected by electrophysiological examination. Before, during,
      or one day after in vitro neuronal differentiation, the hUC-MSCs produced
      granulocyte-colony stimulating factor, vascular endothelial growth factor, glial
      cell line-derived neurotrophic factor, and brain-derived neurotrophic factor. In
      an in vivo study, implantation of the hUC-MSCs into the damaged hemisphere of
      immunosuppressed ischemic stroke rats improved neurobehavioral function and
      reduced infarct volume relative to control rats. Three weeks after implantation,
      most of the implanted hUC-MSCs were present in the damaged hemisphere; some of
      these cells expressed detectable levels of neuron-specific markers. Nestin
      expression in the hippocampus was increased in the hUC-MSC-implanted group
      relative to the control group. Since the hUC-MSCs were both morphologically
      differentiated into neuronal cells and able to produce neurotrophic factors, but
      had not become functionally active neuronal cells, the improvement in
      neurobehavioral function and the reduction of infarct volume might be related to
      the neuroprotective effects of hUC-MSCs rather than the formation of a new
      network between host neurons and the implanted hUC-MSCs.

PMID- 18634758
TI  - Spinal alpha3beta2* nicotinic acetylcholine receptors tonically inhibit the
      transmission of nociceptive mechanical stimuli.
AB  - The presence of non-alpha4beta2, non-alpha7 nicotinic acetylcholine receptors
      (nAChR) in the rat spinal cord has been suggested previously, but the identity of
      these nAChRs had not been shown. Intrathecal administration of the
      alpha3beta2*/alpha6beta2* selective alpha-conotoxin MII (alpha-CTX MII) dose- and
      time-dependently reduced paw withdrawal thresholds to mechanical pressure in
      normal rats. The pronociceptive effect of alpha-CTX MII was partially blocked by
      NMDA receptor antagonism and lost completely following ablation of C-fibers. The
      effect of spinal nerve ligation on alpha-CTX MII-induced mechanical
      hypersensitivity was also assessed. Sensitivity was lost in the hind paw
      ipsilateral to spinal nerve ligation, but maintained in the contralateral hind
      paw at control levels. Radioligand binding in spinal cord membranes revealed high
      and low affinity alpha-CTX MII binding sites. Spinal nerve ligation did not
      significantly alter alpha-CTX MII binding ipsilateral to ligation. Finally, no
      evidence for the presence of alpha6-containing nAChRs was identified. The results
      of these studies show the presence of 2 populations of alpha-CTX MII-sensitive
      nAChRs containing the alpha3 and beta2, but not the alpha6, subunits in the rat
      spinal cord that function to inhibit the transmission of nociceptive mechanical
      stimuli via inhibiting the release of glutamate from C-fibers. Spinal nerve
      ligation produces a unilateral loss of alpha-CTX MII-induced mechanical
      hypersensitivity without altering alpha-CTX MII binding sites. Our data support a
      peripheral injury-induced loss of a cholinergic inhibitory tone at spinal
      alpha3beta2* nAChRs, without the loss of the receptors themselves, which may
      contribute to mechanical hypersensitivity following spinal nerve ligation.

PMID- 18634759
TI  - Specific or general? The nature of attention set changes triggered by distracting
      auditory events.
AB  - Distraction is a disruption of a selective attention set triggered by infrequent,
      unpredictable events. In the present study, two hypotheses on the nature of this
      attention change were contrasted in the auditory domain: (1) distraction is a
      specific attention-switch: attention is diverted from the task-relevant to the
      distracting information or (2) distraction is a general attention resetting, that
      is, a transition to a general attention set in which the organism is more capable
      of facing any event. The general attention resetting hypothesis predicts that any
      infrequent, unpredictable stimulus would trigger distraction, whereas the
      specific attention-switch hypothesis predicts that such a stimulus triggers
      distraction only if it deviates in a task-irrelevant stimulus aspect. To test
      this, a sequence of tone-pairs was presented. The participants' task was to
      respond according to the direction of within-pair pitch-change. Deviant trials
      were presented occasionally (10%). In the Relevant Deviance condition, the
      deviation concerned the task-relevant stimulus aspect (larger within-pair pitch
      difference); in the Irrelevant Deviance condition the deviance occurred in a task
      irrelevant stimulus aspect (spectral width of the second tone of the pair). In
      the Double Deviance condition, deviants featured both a larger pitch-difference
      and a spectral width difference. The elicitation pattern of the N2b/MMN, P3a and
      late negative components favors the specific attention-switch hypothesis, that
      is, distraction comprises an involuntary attention shift from the task-relevant
      information to the distracting one. The presence of deviance-related response
      time delay in the Relevant Deviance condition suggests that other effects
      unrelated to distraction also occurred.

PMID- 18634761
TI  - GABAergic neurons in the ventrolateral subnucleus of the nucleus tractus
      solitarius are in contact with Kolliker-Fuse nucleus neurons projecting to the
      rostral ventral respiratory group and phrenic nucleus in the rat.
AB  - After ipsilateral injections of biotinylated dextran amine (BDA) into the
      ventrolateral subnucleus of the nucleus tractus solitarius (vlNTS) and Fluoro
      gold (FG) into the rostral ventral respiratory group (rVRG) region or into the
      phrenic nucleus (PhN) region in the rat, an overlapping distribution of BDA
      labeled axon terminals and FG-labeled neurons was found in the Kolliker-Fuse (KF)
      nucleus ipsilateral to the injection sites. Using retrograde tracing combined
      with immunohistochemistry for glutamic acid decarboxylase isoform 67 (GAD67), we
      indicated that as many as 40% of the vlNTS neurons projecting to the KF were
      immunoreactive for GAD67. Using a combination of anterograde and retrograde
      tracing techniques, and immunohistochemistry for GAD67, we further demonstrated
      that the vlNTS axon terminals with GAD67 immunoreactivity established close
      contact to the rVRG- or PhN-projecting KF neurons. The present results suggest
      that GABAergic vlNTS fibers may exert inhibitory influences on the rVRG- as well
      as PhN-projecting KF neurons and these circuits may be involved in the
      respiratory reflexes such as the Hering-Breuer reflex.

PMID- 18634762
TI  - Caspase-cleaved TAR DNA-binding protein-43 is a major pathological finding in
      Alzheimer's disease.
AB  - The TAR DNA-binding protein-43 (TDP-43) has been identified as a major
      constituent of inclusions found in frontotemporal dementia with ubiquitin
      positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). To
      determine a possible role for TDP-43 in Alzheimer's disease (AD), a site-directed
      caspase-cleavage antibody to TDP-43 based upon a known caspase-3 cleavage
      consensus site within TDP- 43 at position D219 was designed. In vitro, this
      antibody labeled the predicted 25 kDa caspase-cleavage fragment of TDP-43 without
      labeling full-length TDP-43 following digestion of recombinant TDP-43 with
      caspase-3 or treatment of HeLa cells with staurosporine. Application of this
      antibody in postmortem brain sections indicated the presence of caspase-cleaved
      TDP-43 in Hirano bodies, tangles, reactive astrocytes and neuritic plaques of the
      AD brain. Caspase-cleaved TDP-43 also co-localized with ubiquitin labeled neurons
      as well as dystrophic neurites within plaque regions. These results suggest that
      caspase-cleaved TDP-43 is a major pathological finding in AD and may contribute
      to the neurodegeneration associated with this disease.

PMID- 18634763
TI  - Serotonin immunoreactivity in auditory brainstem neurons of the postnatal
      monoamine oxidase-A knockout mouse.
AB  - Altered levels of extracellular serotonin (5-HT) during development cause
      structural abnormalities in the neural projections of sensory systems. To better
      understand the potential role of 5-HT in the development of auditory system
      projections, we examined 5-HT immunoreactivity (IR) in auditory brainstem nuclei
      of postnatal mice. We previously observed 5-HT-IR in the lateral superior olive
      (LSO) of wild type mice. In the current study, we used a genetic model (monoamine
      oxidase-A knockout mouse) in which brain 5-HT levels are abnormally high to
      improve detection of 5-HT. In the cochlear nucleus of this knockout, 5-HT-IR cell
      bodies were observed in the dorsal cochlear nucleus (DCN), a primary relay to the
      inferior colliculus (IC). In the superior olivary complex, 5-HT-IR somata were
      observed in the LSO, another relay to the IC. Labeled somata were also observed
      within the IC itself. The 5-HT immunostaining in all 3 regions was transient and
      was not observed beyond postnatal day 8. These results suggest that 5-HT may play
      a role in the branching and refinement of DCN and LSO axon collaterals within the
      IC, as well as IC axon collaterals within the medial geniculate body. The pattern
      of expression indicates that 5-HT has a developmental role in select populations
      of neurons of the ascending auditory pathway prior to any influences of sound
      evoked activity.

PMID- 18634764
TI  - The relative timing of active and passive touch.
AB  - Tactile stimulation usually occurs as a combination of an active movement
      (reaching out to touch a surface) and a sensation (actually feeling the surface
      against the skin). The brain has information about the active component (the
      motor command) before it occurs because of efference copy, while the passive
      component must be transduced before it can be processed. Since the active and
      passive tactile components are available to the brain at different times,
      determining the time of touch requires calculation worked backwards from the
      passive sensation, and/or worked forward from the active motor command. In order
      to determine which touch process is perceived more quickly, we varied the
      relative delay between an active and a passive touch signal and determined the
      relative time perceived as simultaneous. A passive touch needed to be presented
      before an active key was pressed in order for the two touches to be perceived as
      simultaneous, but this timing difference was not significant. In order to test
      the plasticity of the active and passive touch systems, we exploited the fact
      that the point of subjective simultaneity between two stimuli can sometimes be
      altered by repeated exposure to asynchronous presentation. We exposed subjects to
      an active key press/ passive touch pair delayed by 250 ms. This exposure
      increased the range of relative delays between active and passive touches at
      which the pairs were judged as simultaneous. This is consistent with an adaptive
      change in the processing of active touch.

PMID- 18634760
TI  - Uncovering genes for cognitive (dys)function and predisposition for alcoholism
      spectrum disorders: a review of human brain oscillations as effective
      endophenotypes.
AB  - Brain oscillations provide a rich source of potentially useful endophenotypes
      (intermediate phenotypes) for psychiatric genetics, as they represent important
      correlates of human information processing and are associated with fundamental
      processes from perception to cognition. These oscillations are highly heritable,
      are modulated by genes controlling neurotransmitters in the brain, and provide
      links to associative and integrative brain functions. These endophenotypes
      represent traits that are less complex and more proximal to gene function than
      either diagnostic labels or traditional cognitive measures, providing a powerful
      strategy in searching for genes in psychiatric disorders. These intermediate
      phenotypes identify both affected and unaffected members of an affected family,
      including offspring at risk, providing a more direct connection with underlying
      biological vulnerability. Our group has utilized heritable neurophysiological
      features (i.e., brain oscillations) as endophenotypes, making it possible to
      identify susceptibility genes that may be difficult to detect with diagnosis
      alone. We have discussed our findings of significant linkage and association
      between brain oscillations and genes in GABAergic, cholinergic and glutamatergic
      systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory
      indices from both resting and active cognitive states have revealed a common
      subset of genetic foci that are shared with the diagnosis of alcoholism and
      related disorders. Implications of our findings have been discussed in the
      context of physiological and pharmacological studies on receptor function. These
      findings underscore the utility of quantitative neurophysiological endophenotypes
      in the study of the genetics of brain function and the genetic diathesis
      underlying complex psychiatric disorders.

PMID- 18634765
TI  - Morphophonological influences on the comprehension of subject-verb agreement: an
      ERP study.
AB  - Event-related potentials were used to study whether factors known to influence
      subject-verb number agreement in production exert analogous effects on sentence
      comprehension. Participants read Dutch sentences containing subject-verb number
      agreement errors while their brainwaves were measured. The determiner of the
      singular head noun could be ambiguous or unambiguous in number and the modifier
      ("local") noun could be plural or singular. Both ambiguity and number match
      affect error rates in production. We expected evoked potentials in response to
      the verb to be modulated by number ambiguity; larger effects were expected when
      the sentences started with an unambiguous determiner. When the local noun was
      singular, we observed a more negative wave elicited by the incorrect verbs
      compared to the correct verbs in the 350-400 ms time-window. This effect was
      largest when the head noun phrase contained no number ambiguity. When the local
      noun was plural the waves were more positive for incorrect verbs than for correct
      verbs in the 600-650 ms time-window. Again this effect was largest when the head
      noun phrase contained no number ambiguity. Most importantly, the results show
      that agreement computation in comprehension is influenced by the same factors as
      in production. We further suggest that in the sentences with a singular local
      noun there is a shallow analysis of the sentence, but the sentences with a plural
      local noun require a deeper syntactic analysis.

PMID- 18634766
TI  - Distortions in the brain? ERP effects of caricaturing familiar and unfamiliar
      faces.
AB  - We report two experiments in which participants classified familiarity and rated
      best-likeness of photorealistic spatial caricatures and anti-caricatures (up to a
      distortion level of 30%) in comparison to veridical pictures of famous faces
      (Experiment 1) and personally familiar faces (Experiment 2). In both experiments
      there was no evidence for a caricature advantage in the behavioural data. In line
      with previous research, caricatures were perceived as worse likenesses than
      veridical pictures and moderate anti-caricatures. In Experiment 2, ERPs for
      familiar faces were largely unaffected by spatial caricaturing, whereas clear
      effects of caricaturing were observed for unfamiliar faces, for which
      caricaturing elicited increased occipito-temporal N170 and N250 responses.
      Whereas increases in N170 amplitude were limited to the first half of the
      experiment, increases in N250 were largest after a number of stimulus repetitions
      in the second half of the experiment. In the second half, ERPs to caricatured
      unfamiliar faces became more similar to ERPs to familiar faces, whereas ERP
      differences between familiar and unfamiliar faces remained prominent for
      veridicals and anti-caricatures. In the context of previous reports of caricature
      effects for line-drawings, these results imply that non-spatial (e.g., texture)
      information plays a prominent role for familiar face recognition, whereas spatial
      caricaturing may be particularly important for the recognition of unfamiliar
      faces, by increasing their distinctiveness.

PMID- 18634767
TI  - Conditioned fear inhibits c-fos mRNA expression in the central extended amygdala.
AB  - We have shown previously that unconditioned stressors inhibit neurons of the
      lateral/capsular division of the central nucleus of the amygdala (CEAl/c) and
      oval division of the bed nucleus of the stria terminalis (BSTov), which form part
      of the central extended amygdala. The current study investigated whether
      conditioned fear inhibits c-fos mRNA expression in these regions. Male rats were
      trained either to associate a visual stimulus (light) with footshock or were
      exposed to the light alone. After training, animals were replaced in the
      apparatus, and 2 h later injected remotely, via a catheter, with amphetamine (2
      mg/kg i.p.), to induce c-fos mRNA and allow inhibition of expression to be
      measured. The rats were then presented with 15 visual stimuli over a 30 minute
      period. As expected, fear conditioned animals that were not injected with
      amphetamine, had extremely low levels of c-fos mRNA in the central extended
      amygdala. In contrast, animals that were trained with the light alone (no fear
      conditioning) and were injected with amphetamine had high levels of c-fos mRNA in
      the CEAl/c and BSTov. Animals that underwent fear conditioning, and were re
      exposed to the conditioned stimulus after amphetamine injection had significantly
      reduced levels of c-fos mRNA in both the BSTov and CEAl/c, compared to the non
      conditioned animals. These data suggest that conditioned fear can inhibit neurons
      of the central extended amygdala. Because these neurons are GABAergic, and
      project to the medial CEA (an amygdaloid output region), this may be a novel
      mechanism whereby conditioned fear potentiates amygdaloid output.

PMID- 18634768
TI  - Localization of phospho-tyrosine489-beta-adducin immunoreactivity in the
      hypothalamic tanycytes and its involvement in energy homeostasis.
AB  - beta-Adducin is a cytoskeletal protein that interacts with the actin filaments to
      suppress actin polymerization and facilitate actin-spectrin binding. We have
      previously shown that beta-adducin is phosphorylated by Fyn at tyrosine489 in the
      rat brain and bound to its Src-homology 2 domain. In the present study, we
      examined the immunohistochemical localization of the tyrosine489-phosphorylated
      form of beta-adducin (pY489-beta-adducin) in the rat brain. Among brain regions,
      highest immunoreactivity was located in the hypothalamic tanycytes that are of
      glial origin lining around the third cerebral ventricle. Their immunoreactive
      processes extended into the arcuate nucleus, ventromedial hypothalamus and the
      median eminence. In addition, the pY489-beta-adducin immunoreactivity in the
      tanycytes was enhanced after fasting for 36-48 h, being associated with a
      morphological change of the DARPP-32-immunoreactivity. Intraperitoneal injection
      of 2-deoxy-d-glucose also enhances pY489-beta-adducin immunoreactivity in the
      tanycytes, along with increased food intake. These results suggest that tyrosine
      phosphorylation of beta-adducin in the tanycytes is involved in hypothalamic
      regulation of food intake and energy homeostasis.

PMID- 18634769
TI  - Individual and additive effects of neuromodulators on the slow components of
      afterhyperpolarization currents in layer V pyramidal cells of the rat medial
      prefrontal cortex.
AB  - The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine (DA) and
      the muscarinic receptor agonist carbachol (CCh) on the voltage step-induced
      outward currents underlying afterhyperpolarization (AHP), consisting of a medium
      (I(mAHP)) and slow (I(sAHP)) component, were investigated in layer V pyramidal
      cells of the rat medial prefrontal cortex (mPFC). Whole-cell voltage clamp
      recordings were performed in vitro to quantitatively measure I(mAHP) and I(sAHP)
      and to examine their functional link to spike-frequency adaptation in the
      presence of agonists. CCh, 5-HT and NA all reduced the I(sAHP) and the spike
      adaptation, and, in some cells, replaced the I(sAHP) by the slow inward currents
      (I(sADP)) underlying the slow afterdepolarization (sADP). DA, however, failed to
      increase the frequency despite its comparable inhibition of the I(sAHP) over a
      range of concentrations. In order to test the neuromodulator agonists to see if
      they have additive actions on the I(sAHP), the effects of co-application of two
      agonists that increased spike-frequency, 5-HT+NA, 5-HT+CCh and CCh+NA, all at the
      concentration 30 microM were examined. Specific combinations that included CCh
      showed additive effects on the slow afterpolarization currents, possibly via both
      inhibition of I(sAHP) and generation of I(sADP). These findings suggest that
      neuromodulators have differential effects on the link between the I(sAHP)
      modulation and spike-frequency adaptation, and that they could exert additive
      effects on the slow aftercurrents following a strong excitation and, therefore,
      regulate the repetitive firing properties of the output cells of the rat mPFC.

PMID- 18634770
TI  - Randomized comparison of early inflammatory response after sirolimus-eluting
      stent vs bare metal stent implantation in native coronary lesions.
AB  - BACKGROUND: The clinical significance of early inflammatory response after
      coronary stent implantation has been controversial. Sirolimus-eluting stent (SES)
      has been shown to be better outcomes compared with bare metal stent (BMS). We
      prospectively investigated the early inflammatory response after SES or BMS
      implantation in patients with single-vessel lesion, and evaluated the
      relationship between inflammation and late clinical outcomes in a randomized
      design. METHODS: Forty-eight patients with single-vessel disease were randomized
      into SES or BMS implantation group (n=24 respectively). Blood samples were taken
      before stenting, 1 h, 24 h and 8 months afterward. The plasma concentrations of C
      reactive protein (CRP) and interleukin-6 (IL-6) were determined by ELISA. The
      clinical and angiographic follow-up were performed at 8 months after stenting.
      RESULTS: There was no difference in baseline characteristics, plasma CRP and IL-6
      concentrations between the 2 groups. However, plasma IL-6 concentrations at 1 h
      after stenting were higher in both groups than in baseline (p<0.01). In addition,
      the plasma CRP and IL-6 concentrations at 24 h after stenting were significantly
      higher in both groups compared with baseline (p<0.01 respectively). Likewise,
      plasma CRP and IL-6 concentrations were significantly higher in BMS group
      compared with SES group at 24 h after stenting (p<0.05 respectively). At the
      follow-up (mean 8 months after stenting), the rate of in-stent restenosis (ISR)
      and target lesion revascularization (TLR) were higher in BMS group than in SES
      group (p<0.05 respectively) although the plasma CRP and IL-6 concentrations are
      similar between the groups. CONCLUSIONS: Single coronary stenting could trigger
      an early inflammatory response. However, patients undergoing SES implantation has
      less augmentation of early inflammatory markers after stenting compared to
      patients treated with BMS, which was positively related the incidence of ISR and
      TLR at follow-up. This may reflect the potential impact of SES implantation on
      the early inflammatory response and late clinical outcomes.

PMID- 18634771
TI  - A rapid LC-FTMS method for the analysis of cysteine, cystine and cysteine/cystine
      steady-state redox potential in human plasma.
AB  - BACKGROUND: The steady-state redox potential of the cysteine/cystine couple in
      human plasma provides a measure of oxidative stress, yet available assays are
      limited by either specificity or speed of assay. METHOD: The present study
      evaluated the use of LC-FTMS for identification based on accurate mass combined
      with quantification by stable isotopic dilution to rapidly determine cysteine and
      cystine concentration and cysteine/cystine steady-state redox potential in human
      plasma. RESULTS: A simple extraction procedure followed by a rapid LC separation
      eluted cysteine in 4 min and cystine in 1.5 min with simultaneous measurement of
      glutathione (GSH) and glutathione disulfide (GSSG). A study of five young (mean
      age=25.7) subjects and 5 older (mean age=67.8 y) subjects showed an increased
      oxidation with age. CONCLUSIONS: The analysis by LC-FTMS is suitable for high
      throughput analysis of plasma cysteine, cystine and cysteine/cystine steady-state
      redox potential as clinical measures of oxidative stress.

PMID- 18634772
TI  - PON1 status is influenced by oxidative stress and inflammation in coronary heart
      disease patients.
AB  - OBJECTIVES: High-density lipoprotein (HDL) associated paraoxonase 1 (PON1) is an
      essential component of HDLs' capability to protect low-density lipoproteins (LDL)
      from oxidative modification and thus to limit the atherosclerotic process. The
      aim of the current study was to investigate the association between oxidative
      stress status, indices of inflammation and PON1 status parameters. DESIGN AND
      METHODS: We determined the relationship between the oxidative stress status,
      inflammatory markers and PON1 status parameters in 261 middle-aged subjects: 156
      coronary heart disease (CHD) patients and 105 CHD-free subjects (as the control
      group). The PON1 status involved PON1 activity measurements towards two
      substrates: paraoxon (POase activity) and diazoxon (DZOase activity) and
      subsequent PON1(Q192R) activity phenotype determination. RESULTS: A statistically
      significant greater malondialdehyde (MDA) concentration in the RR phenotype
      subjects compared to QQ subjects within the CHD group was apparent (P<0.05).
      Multiple linear regression analysis revealed an independent influence of
      plasmatic SOD activity (P<0.05) on POase values and MDA (P<0.01) and O(2)(-)
      (P<0.05) on DZOase values. Involvement of inflammatory markers (fibrinogen and
      hsCRP) in the regression model did not hinder the influence of SOD and MDA on
      POase and DZOase activities, respectively. CONCLUSIONS: Our CHD patients were in
      a state of oxidative stress, which was most evident in the RR phenotype group.
      The QQ phenotype group is associated with the lowest oxidative stress status
      level and also with a better capacity for anti-oxidative protection. Oxidative
      stress in CHD patients is maintained by systemic low-grade inflammation, which
      results in PON1 enzymatic activity exhaustion. Therefore, deeper investigation of
      an effective anti-oxidative and anti-inflammatory therapy should be necessary in
      order to increase anti-oxidative potency and improve PON1 status of CHD patients.

PMID- 18634773
TI  - ATP, calcium and magnesium levels in platelets of patients with primary
      fibromyalgia.
AB  - OBJECTIVES: To evaluate the intracellular levels of the high energy adenosine
      triphosphate nucleotide ATP and essential divalent cations, calcium and
      magnesium, in platelets of patients affected by primary fibromyalgia syndrome
      (FMs). DESIGN AND METHOD: Platelet ATP and cation concentrations were measured in
      25 patients affected by FMs and 25 healthy volunteers through a chemiluminescent
      and a fluorimetric assay, respectively. RESULTS: Significant lower ATP levels
      were observed inside platelets of FM patients (fmol ATP/plt: 0.0169+/-0.0012 vs.
      healthy controls, fmol ATP/plt: 0.0306+/-0.0023, mean+/-SEM) (*** P<0.0001). A
      trend towards higher calcium concentrations (P=0.06) together with significant
      increased magnesium levels were also reported in platelets of patients by
      comparison with controls (P=0.02). CONCLUSIONS: This preliminary study suggests
      that disturbances in the homeostasis of platelet ATP metabolism-signaling and
      calcium-magnesium flows might have a relevance in the pathogenesis of FMs.

PMID- 18634774
TI  - Autophosphorylation of H2AX in a cell-specific frozen dependent way.
AB  - Effective cryopreservation is a highly desired outcome in many laboratories
      including clinical and research centers. Cryopreservation-induced cellular damage
      through necrosis and apoptosis has been well characterized. However, our
      knowledge of the mechanism of induction of these cell death modalities is
      limited. H2AX histone phosphorylation to gamma-H2AX is a DNA damage response and
      is an excellent indicator of DNA double stranded break formation. In this study
      we examined and detected significant phosphorylation of H2AX in response to
      cryopreservation of HELF and B16 cell lines. The data provide strong evidence of
      intrinsic alterations in DNA repair pathway members for which the impact is yet
      to be fully understood. While further investigation will be necessary to
      characterize this response, our findings show a clear linkage between freezing
      resulting in phosphorylation and activation of the key DNA repair enzyme H2AX.

PMID- 18634775
TI  - Facial clefting in Tp63 deficient mice results from altered Bmp4, Fgf8 and Shh
      signaling.
AB  - During embryogenesis, the transcription factor Tp63 is expressed in the basal
      cells of multiple epithelial tissues. In humans, mutations in TP63 have been
      identified in five distinct human developmental disorders that are characterized
      by limb abnormalities, ectodermal dysplasia, and facial anomalies. To dissect the
      molecular pathogenesis of the bilateral cleft lip and cleft palate that results
      from mutation of Tp63, we analysed Tp63 mutant mice. At E10.5, Tp63-deficient
      mice exhibited abnormal morphogenesis of the medial nasal, lateral nasal and
      maxillary processes. Analysis of key signaling molecules revealed that these
      defects result from increased Bmp4 signaling in the epithelia of the facial
      processes. Acting antagonistically on Fgf8 and Shh, this aberrant signaling led
      to a reduction in mesenchymal cell proliferation and increased cell death in
      specific regions of the facial processes. In addition, a proliferative defect in
      the mesenchyme of the maxillary processes at E11.5 resulted in absence of the
      anterior region of the palatal shelves and, subsequently, cleft palate. Our
      results are consistent with a role for Tp63 in the regulation of Bmp signaling
      controlling the growth, modelling and fusion events underlying facial development
      and shed new light on the complex abnormality of facial clefting.

PMID- 18634776
TI  - An increase in intracellular Ca2+ is involved in pronephric tubule
      differentiation in the amphibian Xenopus laevis.
AB  - The pronephros is the first kidney to develop and is the functional embryonic
      kidney in lower vertebrates. It has previously been shown that pronephric tubules
      can be induced to form ex vivo in ectodermal tissue by treatment with activin A
      and retinoic acid. In this study, we investigated the role of Ca(2+) signaling in
      the formation of the pronephric tubules both in intact Xenopus embryos and ex
      vivo. In the ex vivo system, retinoic acid but not activin A stimulated the
      generation of Ca(2+) transients during tubule formation. Furthermore, tubule
      differentiation could be induced by agents that increase the concentration of
      intracellular Ca(2+) in activin A-treated ectoderm. In addition, tubule formation
      was inhibited by loading the ectodermal tissue with the Ca(2+) chelator, BAPTA-AM
      prior to activin A/retinoic acid treatment. In intact embryos, Ca(2+) transients
      were also recorded during tubule formation, and photo-activation of the caged
      Ca(2+) chelator, diazo-2, localized to the pronephric domain, produced embryos
      with a shortened and widened tubule phenotype. In addition, the location of the
      Ca(2+) transients observed, correlated with the expression pattern of the
      specific pronephric tubule gene, XSMP-30. These data indicate that Ca(2+) might
      be a necessary signal in the process of tubulogenesis both ex vivo and in intact
      embryos.

PMID- 18634777
TI  - Ptf1a, Lbx1 and Pax2 coordinate glycinergic and peptidergic transmitter
      phenotypes in dorsal spinal inhibitory neurons.
AB  - Inhibitory neurons in the dorsal horn synthesize a variety of neurotransmitters,
      including GABA, glycine and a set of peptides. Here we show that three
      transcription factors, Ptf1a, Pax2, and Lbx1, which have been reported to promote
      a GABAergic cell fate, also specify glycinergic and peptidergic transmitter
      phenotypes. First, Ptf1a appears to be a master regulator, as indicated by a
      requirement of Ptf1a for the expression of glycinergic marker GlyT2 and a set of
      peptides, including neuropeptide Y (NPY), nociceptin/orphanin FQ (N/OFQ),
      somatostatin (SOM), enkephalin (ENK), dynorphin (DYN) and galanin (GAL). Second,
      Pax2 is a downstream target of Ptf1a and controls subsets of transmitter
      phenotypes, including the expression of GlyT2, NPY, N/OFQ, DYN, and GAL, but is
      dispensable for SOM or ENK expression. Third, for Lbx1, due to neuronal cell loss
      at late stages, our analyses focused on early embryonic stages, and we found that
      Lbx1 is required for the expression of GlyT2, NPY, N/OFQ and is partially
      responsible for SOM expression. Our studies therefore suggest a coordinated and
      hierarchical specification of a variety of neurotransmitters in dorsal spinal
      inhibitory neurons.

PMID- 18634778
TI  - Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular
      dysfunction in renovascular hypertensive rats.
AB  - Increased expression/activity of matrix metalloproteinases (MMPs), especially MMP
      2, plays a role in the vascular alterations induced by hypertension, and
      increased oxidative stress is a major factor activating MMPs. Here, we
      hypothesized that lercanidipine, a calcium channel blocker, could attenuate the
      increases in oxidative stress and MMP-2 expression/activity in the two-kidney,
      one-clip (2K-1C) hypertensive rats. Sham-operated or 2K-1C hypertension rats were
      treated with lercanidipine 2.5 mg/kg/day (or vehicle) starting three weeks after
      hypertension was induced. Systolic blood pressure was monitored weekly. After
      five weeks of treatment, aortic rings were isolated to assess endothelium
      dependent and independent relaxations. Quantitative morphometry of structural
      changes in the aortic wall were studied in hematoxylin/eosin sections. Aortic MMP
      2 levels were determined by gelatin zymography. Aortic MMP-2/tissue inhibitor of
      metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real-time
      RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were
      determined using a fluorometric method. Lercanidipine attenuated 2K-1C
      hypertension (224+/-12 versus 183+/-11 mm Hg in 2K-1C rats and 2K-1C +
      Lercandipine rats, respectively; P<0.01) and prevented the reduction in
      endothelium-dependent vasorelaxation found in 2K-1C rats. Increased MMP-2 and Pro
      MMP-2 levels were found in the aortas of 2K-1C rats (all P<0.05). Lercandipine
      attenuated 2K-1C-induced increases in MMP-2 by more than 60% and blunted 2K-1C
      induced increases in oxidative stress (both P<0.001). While hypertension-induced
      significant aortic wall hypertrophy and approximately 9-fold increases in the
      ratio of MMP-2/TIMP-2 mRNA expression (both P<0.05), lercandipine did not affect
      these changes. These results suggest that lercanidipine produces antihypertensive
      effects and reverses the endothelial dysfunction associated with 2K-1C
      hypertension, probably through mechanisms involving antioxidant effects leading
      to lower MMP-2 activation.

PMID- 18634779
TI  - Calcium extrusion by plasma membrane calcium pump is impaired in caveolin-1
      knockout mouse small intestine.
AB  - Plasma membrane calcium ATPase (PMCA) is an important calcium extrusion mechanism
      in smooth muscle cells. PMCA4 is the predominant isoform operating in conditions
      of high intracellular calcium during contraction. PMCA appears to be localized in
      lipid rafts and caveolae. In this study we examined the effects of the PMCA4
      selective inhibitor caloxin 1c2 (5 microM) in intestine of caveolin-1 knockout
      mice and in bovine tracheal smooth muscle after caveolae disruption on PMCA4
      function. Small intestinal tissues from control mice treated with caloxin 1c2
      showed a higher contractile response of the longitudinal smooth muscle to
      Carbachol (10 microM) when compared to control tissues treated with a similar
      concentration of a control peptide. This effect of caloxin 1c2 was not found in
      tissues from caveolin-1 knockout mice. Immunohistochemistry and Western blotting
      of membrane fractions showed that PMCA was co-localized with caveolin-1 in smooth
      muscle plasma membrane in control tissues. One of the PMCA4 splice variant bands
      was missing in the lipid raft-enriched fraction prepared from caveolin-1 knockout
      tissue. In bovine tracheal smooth muscle tissue, caveolae disruption by
      cholesterol depletion led to the diminution of caveolin-1 and PMCA4b
      immunoreactivities, previously co-localized in the smooth muscle plasma membrane,
      and to the loss of the increase in Carbachol-induced contraction by caloxin 1c2.
      Our results suggest that the calcium removal function of PMCA4 in smooth muscle
      cells is dependent on its presence in intact caveolae. We suggest that this is
      due to the close spatial arrangement that allows calcium extrusion from a
      privileged cytosolic space between caveolae and sarcoplasmic reticulum.

PMID- 18634780
TI  - Clomipramine block of the hERG K+ channel: accessibility to F656 and Y652.
AB  - Clomipramine is a tricyclic antidepressant for psychiatric disorders that can
      induce QT prolongation, which may lead to torsades de pointes. Since blockade of
      cardiac human ether-a-go-go-related gene (hERG) channels is an important cause of
      acquired long QT syndrome, we investigated the acute effects of clomipramine on
      hERG channels to determine the electrophysiological basis for its proarrhythmic
      potential. We examined the effects of clomipramine on the hERG channels expressed
      in Xenopus oocytes and HEK293 cells using two-microelectrode voltage-clamp and
      patch-clamp techniques. Clomipramine induced a concentration-dependent decrease
      in the current amplitude at the end of the voltage steps and hERG tail currents.
      The IC50 for clomipramine needed to block the hERG current in Xenopus oocytes
      decreased progressively relative to the degree of depolarization. The fractional
      electrical distance was estimated to be delta=0.83. The IC50 for the clomipramine
      induced blockade of the hERG currents in HEK293 cells at 36 degrees C was 0.13
      microM at +20 mV. Clomipramine affected the channels in the activated and
      inactivated states but not in the closed states. The clomipramine-induced
      blockade of hERG was found to be use-dependent, exhibiting a more rapid onset and
      a greater steady-state block at the higher frequencies of activation. The S6
      domain mutations, Y652A and F656A partially attenuated (Y652A) or abolished
      (F656A) the hERG-current blockade. These results suggest that clomipramine is a
      blocker of the hERG channels, providing a molecular mechanism for the
      arrhythmogenic side effects during the clinical administration of clomipramine.

PMID- 18634781
TI  - Behavioral characterization of the mGlu group II/III receptor antagonist, LY
      341495, in animal models of anxiety and depression.
AB  - There is a growing body of evidence indicating that stimulation of metabotropic
      glutamate type II receptors (mGlu2/3) reduces anxiety in laboratory animals and
      humans. Surprisingly, it was reported that mGlu2/3 receptor antagonists have
      antidepressant- and anxiolytic-like activities in laboratory animal studies as
      well. The present study aimed to resolve this controversy by characterizing
      behavioral effects of a selective mGlu2/3 receptor antagonist, LY-341495, in a
      variety of animal models sensitive to clinically used anxiolytic and
      antidepressant agents. In agreement with previous reports, LY-341495 (0.3-3
      mg/kg, i.p.) reduced immobility in the mouse forced swim test. LY-341495 was also
      effective in the marble burying test in mice, although similar effects were
      observed after administration of various drugs including methamphetamine.
      Further, LY-341495 had no effects in the elevated plus maze and stress-induced
      hyperthermia tests in mice, as well as on punished drinking (Geller-Seifter's
      test) and differential reinforcement of low rates of responding (DRL) in rats. It
      is concluded that behavioral profile of mGlu2/3 receptor antagonists as
      represented by LY-341495 is different from that of conventional anxiolytic and
      antidepressant drugs.

PMID- 18634782
TI  - The role of the N-terminal and mid-region residues of substance P in regulating
      functional selectivity at the tachykinin NK1 receptor.
AB  - Previous studies have shown that tachykinin peptide ligands of the tachykinin NK1
      receptor exhibit functional selectivity with respect to signal activation and
      desensitization. The differences are most dramatic between the naturally
      occurring peptides substance P (RPKPQQFFGLM-NH2) and ranatachykinin C (HNPASFIGLM
      NH2). To understand the structural features of the peptides that underlie these
      differences, four peptide analogs have been designed and tested. The analogs were
      designed to assess the major structural differences between substance P and
      ranatachykinin C, including the role of the N-terminal Arg and the substitution
      of the mid-region Glns with Ala and Ser (Q5 replaced with A and/or Q6 replaced
      with S). Receptor binding, receptor activation of intracellular calcium fluxes,
      and receptor desensitization of the rat tachykinin NK1 receptor were quantified
      for each ligand. All of the peptides bound to the rat tachykinin NK1 receptor
      with high affinity, produced robust calcium signal activation, and led to agonist
      induced receptor desensitization. It was found that deletion of the N-terminal
      Arg of substance P or replacement of either or both Q5 and Q6 altered the
      functional selectivity of substance P based on the relationship of receptor
      binding to receptor activation and activation to desensitization. When considered
      in light of our previously published nuclear magnetic resonance structure data,
      the data presented herein suggest that the one, five and six positions of the
      substance P backbone are key structural residues that govern the relative degree
      of tachykinin peptide-mediated receptor signaling and desensitization.

PMID- 18634783
TI  - Sorting of the v-SNARE VAMP7 in Dictyostelium discoideum: a role for more than
      one Adaptor Protein (AP) complex.
AB  - Soluble N-ethylmaleimide-sensitive-factor Attachment protein Receptors (SNAREs)
      participate in the specificity of membrane fusions in the cell. The mechanisms of
      specific SNARE sorting are still however poorly documented. We investigated the
      possible role of Adaptor Protein (AP) complexes in sorting of the Dictyostelium
      discoideum v-SNARE VAMP7. In live cells, GFP-VAMP7 is observed in the membrane of
      endocytic compartments. It is also observed in the plasma membrane of a small
      proportion of the cells. Mutation of a potential dileucine motif dramatically
      increases the proportion of cells with GFP-VAMP7 in their plasma membrane,
      strongly supporting the participation of an AP complex in VAMP7 sorting to the
      endocytic pathway. A partial increase occurs in knockout cells for the medium
      subunits of AP-2 and AP-3 complexes, indicating a role for both AP-2 and AP-3.
      VAMP7, as well as its t-SNAREs partners syntaxin 8 and Vti1, are co
      immunoprecipitated with each of the medium subunits of the AP-1, AP-2, AP-3 and
      AP-4 complexes. This result supports the conclusion that VAMP7 directly interacts
      with both AP-2 and AP-3. It also raises the hypothesis of an interaction with AP
      1 and AP-4. GFP-VAMP7 is retrieved from the endocytic pathway at and/or before
      the late post-lysosomal stage through an AP-independent mechanism.

PMID- 18634784
TI  - A clinical grading system for retinal inflammation in the chronic model of
      experimental autoimmune uveoretinitis using digital fundus images.
AB  - Experimental autoimmune uveoretinitis (EAU), a widely used animal model of human
      posterior/pan-uveitis, is extremely valuable in allowing understanding of the
      pathogenesis of uveitis as well as in developing new treatments. Depending on the
      animal strain and immunization protocol used, the clinical course of EAU can be
      acute, severe and involving the anterior and posterior part of the eye, or
      chronic, mild and involving only the posterior part of the eye. Clinical signs of
      EAU can be examined by bio-microscopy. Using appropriate criteria EAU can be
      quantitatively evaluated clinically in living animals. However, correlation of
      research within different laboratories is difficult since clinical grading
      systems are subjective and susceptible to considerable variability. In this
      study, we have developed a recordable, image-based clinical grading system for
      the chronic models of EAU. Fundus images were taken from EAU mice using an
      endoscopic imaging system. Fundus changes were classified as (1) inflammatory
      changes (including optic disc inflammation, vasculitis and retinal tissue
      inflammation) and (2) retinal structural damage. Each element was scored
      separately based on the severity of the lesions, and the average score of the
      three inflammatory elements was used as the overall EAU clinical inflammation
      grade of the eye. The validity and reproducibility of the grading system was
      tested using a set of images scored independently in a masked manner by 5
      individuals. The grading system proved robust, easy to use and reliable. We offer
      this image-based EAU clinical grading system as a useful quantitative evaluation
      method for clinical grading of the severity of inflammation in the chronic EAU
      model, in which the inflammation can be mild and mainly involves posterior part
      of the eye.

PMID- 18634785
TI  - Toxoplasma gondii: an improved rat model of congenital infection.
AB  - The objective of this study was to refine the rat model of congenital
      toxoplasmosis. In Fischer rats we found that visualization of spermatozoa in
      vaginal exudates and the detection of at least 6g body weight increase between
      days 9 and 12 of pregnancy, allowed the diagnosis and timing of pregnancy with
      60% specificity and 84% sensitivity. A dose of 10(4) Toxoplasma gondii
      bradyzoites or 10(2) T. gondii oocysts of the Prugniaud strain resulted in more
      than 50% of congenital infection of the rat litters. Transmission of T. gondii
      via lactation was not detected in rats inoculated with either bradyzoites or
      oocysts. Bioassays of 51 neonates born from mothers inoculated with bradyzoites
      (in tissue cysts) and 29 neonates from mothers inoculated with oocysts
      demonstrated that both liver and lungs can be used for the diagnosis of
      congenital transmission in this model.

PMID- 18634786
TI  - Protein phosphatase 4 negatively regulates LPS cascade by inhibiting
      ubiquitination of TRAF6.
AB  - TRAF6 is an E3 ubiquitin ligase that transduces signals from members of the
      TLR/IL-1R family. Multiple molecules have been found to associate with TRAF6 and
      exert their functions in this pathway. Herein, by yeast two-hybrid screen using
      TRAF6 as bait, we identified PP4 as a potential TRAF6-interacting protein. PP4
      physically interacted with TRAF6 and was recruited to TLR4 complex upon LPS
      stimulation. PP4 negatively regulated LPS-induced and TRAF6-mediated NF-kappaB
      activation by inhibiting the ubiquitination of TRAF6. LPS stimulation also
      induced the expression of PP4. Taken together, our findings suggest that PP4 is a
      negative feedback regulator of LPS/TLR4 pathway.

PMID- 18634787
TI  - If it reduces stress (hormones), do it!

PMID- 18634788
TI  - Olfactory neuron responsiveness and pheromone blend preference in hybrids between
      Ostrinia furnacalis and Ostrinia nubilalis (Lepidoptera: Crambidae).
AB  - The olfactory receptor neuron (ORN) and behavioral responses of hybrids between
      the Asian corn borer (ACB), Ostrinia furnacalis, and the E-strain European corn
      borer (ECB(E)), Ostrinia nubilalis were examined and compared to the parental
      populations. In hybrids and both parents, the large-spike-size ORN was capable of
      responding to all four pheromone components of ACB and ECB, despite differences
      in which compounds elicited the greatest spike frequency in each population.
      There was a small-spiking ORN more narrowly tuned to the minor pheromone
      components in both ACB and ECB(E). In hybrids the homologous small-spiking ORN
      was tuned primarily to the ECB(E) minor pheromone component, with some
      responsiveness to the ACB minor component. Both species and all the hybrids had
      an intermediate spike-size ORN tuned primarily to their common behavioral
      antagonist. Dominance of responsiveness to the ECB(E) versus the ACB minor
      pheromone component on the small-spiking ORN may explain the greater tendency of
      hybrids to fly upwind to the ECB(E) pheromone blend than the ACB blend. This
      finding points toward a distinct evolutionary role for this ORN in allowing a
      pheromone shift.

PMID- 18634789
TI  - Cloning and expression analysis of midgut chymotrypsin-like proteinases in the
      tobacco hornworm.
AB  - Digestion of proteins in the midgut of lepidopteran larvae relies on different
      trypsin and chymotrypsin isoforms. In this study we describe three chymotrypsin
      like proteinases (CTLP2-4) from the larval midgut of Manduca sexta, which are
      closely related to CTLP1 and less closely related to another chymotrypsin (CT),
      two previously described proteinases present in the larval midgut of M. sexta.
      CTLP1-4 fit perfectly into a novel subgroup of insect CTLPs by sequence
      similarity and by the replacement of GP by SA in the highly conserved GDSGGP
      motif. When we examined CTLP expression in different tissues, most of the
      proteinases were predominantly expressed in the anterior and median midgut, while
      some were found in the Malpighian tubules. When we examined CTLP expression at
      different physiological states, we observed that the CTLP mRNA amounts did not
      differ considerably in feeding and starving larvae except for CTLP2, whose mRNA
      dropped significantly upon starvation. During moulting, however, the mRNA amounts
      of all CTLPs dropped significantly. When we immunologically examined CTLP
      amounts, mature proteinases were only detectable in the gut lumen of feeding and
      re-fed larvae, but not in that of starving or moulting larvae, suggesting that
      CTLP secretion is suspended during starvation or moult.

PMID- 18634790
TI  - UV radiation elevates arylalkylamine N-acetyltransferase activity and melatonin
      content in the two-spotted spider mite, Tetranychus urticae.
AB  - Ultraviolet (UV) radiation produces reactive oxygen species (ROS) in mammals,
      where melatonin plays the role of a ROS scavenger. The melatonin synthetic enzyme
      arylalkylamine N-acetyltransferase (NAT) is a significant element in a possible
      ROS removal system. Changes in NAT activity and melatonin content were determined
      in the two-spotted spider mite Tetranychus urticae by irradiating it with
      monochromatic light using the Okazaki Large Spectrograph at the National
      Institute for Basic Biology, Okazaki, Japan. The NAT activity and melatonin
      content were suppressed by blue light (450nm). No effects of red light (650nm) on
      the NAT activity and melatonin content were observed. UV radiation had intensity
      dependent dual effects on the NAT activity and melatonin content. In the UV-B
      (300nm) treatment, the NAT activity and melatonin content were suppressed at the
      intensity below 1micromolm(-2)s(-1) but elevated when the intensity was as high
      as 10micromolm(-2)s(-1). In the UV-A (350nm) treatment, the melatonin content was
      elevated when the intensity was as high as 10micromolm(-2)s(-1), though the NAT
      activity and melatonin content were suppressed at the intensity below 10 and
      1micromolm(-2)s(-1), respectively. Elevation of the NAT activity and melatonin
      content by high intensity UV irradiation may indicate that the UV signals
      initiate melatonin synthesis for ROS removal in mites.

PMID- 18634791
TI  - Attraction of female Culex quinquefasciatus Say (Diptera: Culicidae) to odors
      from chicken feces.
AB  - Odors from fresh chicken feces in water elicited upwind flight of host-seeking
      female Culex quinquefasciatus mosquitoes in a dual-choice olfactometer.
      Acidification of the slurry of chicken feces and water resulted in increased
      attraction, whereas alkaline slurries of chicken feces and water controls did not
      attract female mosquitoes. This is the first reported example of avian fecal odor
      eliciting upwind flight of female mosquitoes. Headspace odors from acidified
      slurries were sampled using solid phase micro-extraction (SPME) coated fibers.
      Eight volatile aldehydes [(E)-2-decenal, undecanal, dodecanal, tetradecanal,
      pentadecanal, hexadecanal, heptadecanal, and octadecanal] identified in the
      headspace of acidified chicken feces elicited electroantennogram responses from
      antennae of C. quinquefasciatus females. An improved electroantennogram technique
      in which four antennae were used in parallel for monitoring the GC effluent is
      described.

PMID- 18634792
TI  - Nutrient content of diet affects the signaling activity of the insulin/target of
      rapamycin/p70 S6 kinase pathway in the African malaria mosquito Anopheles
      gambiae.
AB  - Regulation of female mosquito feeding and reproduction plays a central role in
      their disease-vector competence. In this study we show that Anopheles gambiae
      mosquitoes engorged on albumin, amino acid and saline meals the same way as on
      blood, whereas sucrose evoked a typical plant nectar feeding response. Among the
      artificial diets, only the albumin-containing ones allowed follicular
      development. The target of rapamycin (TOR)/p70 S6 kinase (S6K) pathway has been
      identified as an essential nutrient-sensing tool controlling egg development in
      mosquitoes under the control of regulating inputs from the insulin pathway. We
      assayed the early response of TOR, S6K, tuberous sclerosis (TSC2), insulin
      receptor (INR) and two insulin-like peptides (ILPs) by quantitative real-time PCR
      assessment of mRNA levels and immunoblotting of phosphorylated active TOR and S6K
      in An. gambiae ovary and brain 3 h after engorgement. We show that transcript
      levels of s6k and members of the insulin pathway are readily affected by
      nutrients (especially one ILP in the head) and that the TOR/S6K phosphorylation
      is able to react quickly to a meal to an extent which depends on the true
      nutritive value.

PMID- 18634793
TI  - Tissue and stage-specific juvenile hormone esterase (JHE) and epoxide hydrolase
      (JHEH) enzyme activities and Jhe transcript abundance in lines of the cricket
      Gryllus assimilis artificially selected for plasma JHE activity: implications for
      JHE microevolution.
AB  - Fat body and midgut juvenile hormone esterase (JHE) and juvenile hormone epoxide
      hydrolase (JHEH) specific activities, and plasma JHE activity, were measured
      throughout the last stadium in two pairs (blocks) of lines of the cricket Gryllus
      assimilis, each pair of which had been artificially selected for high- or low
      plasma JHE activity. Highly significant differences were observed between high-
      and low-activity lines of each block on most days for fat body JHE, and on one
      day for midgut JHE activity. In each block, line differences in developmental
      profiles for fat body JHE activity paralleled line differences in plasma JHE
      activity during the early-mid stadium, but not during the latter part of the
      stadium. The developmental profile of midgut JHE activity differed from that of
      plasma and fat body JHE activity, exhibiting peaks during the early and latter
      parts of the stadium. Midgut and fat body JHEH activities exhibited a mid-stadium
      peak in all lines, but activities were very similar in all lines. Fat body JHE
      appears to be a more significant contributor to plasma JHE than is midgut JHE.
      During the middle of the last stadium (day 4), Jhe transcript abundance was
      significantly higher in fat body or midgut of high- vs. low-JHE-activity lines.
      Jhe transcript abundance was positively correlated with JHE enzyme activity in
      either fat body or midgut, and with plasma JHE activity. Natural populations of
      G. assimilis harbor genetic variation for Jhe gene expression which appears to
      contribute to genetic variation in JHE specific activity in fat body and midgut.
      These genes appear to have been the targets of artificial selection that resulted
      in lines that differ dramatically in high- or low-plasma JHE activity. These
      genes appear to have little, if any, pleiotropic effects on JHEH specific
      activity.

PMID- 18634794
TI  - Effects of temperature on reproductive output, egg provisioning, juvenile hormone
      and vitellogenin titres in the butterfly Bicyclus anynana.
AB  - Environmentally induced phenotypic plasticity is common in nature. Hormones,
      affecting multiple traits and signaling to a variety of distant target tissues,
      provide a mechanistic link between environments, genes and trait expression, and
      may therefore well be involved in the regulation phenotypic plasticity. Here, we
      investigate whether in the tropical butterfly Bicyclus anynana temperature
      mediated plasticity in egg size and number, with fewer but larger eggs produced
      at lower temperatures and vice versa, is under control of juvenile hormone, and
      whether different temperatures cause differences in egg composition. Female B.
      anynana butterflies showed the expected response to temperature, however, we
      found no evidence for an involvement of juvenile hormone. Neither haemolymph JH
      II and JH III titres nor vitellogenin levels differed across temperatures. The
      smaller eggs produced at the higher temperature contained relatively higher
      amounts of water, free carbohydrates and proteins, but relatively lower amounts
      of lipids. While these smaller eggs had a lower absolute energy content, total
      reproductive investment was higher at the higher temperature (due to a higher
      fecundity). Overall, our study indicates that temperature-mediated plasticity in
      reproduction in B. anynana is mechanistically related to a biophysical model,
      with oocyte production (differentiation) and oocyte growth (vitellogenesis)
      having differential temperature sensitivities.

PMID- 18634795
TI  - Characterization of PDF-immunoreactive neurons in the optic lobe and cerebral
      lobe of the cricket, Gryllus bimaculatus.
AB  - Pigment-dispersing factor (PDF) is a neuropeptide playing important roles in
      insect circadian systems. In this study, we morphologically and physiologically
      characterized PDF-immunoreactive neurons in the optic lobe and the brain of the
      cricket Gryllus bimaculatus. PDF-immunoreactivity was detected in cells located
      in the proximal medulla (PDFMe cells) and those in the dorsal and ventral regions
      of the outer chiasma (PDFLa cells). The PDFMe cells had varicose processes spread
      over the frontal surface of the medulla and the PDFLa cells had varicose mesh
      like innervations in almost whole lamina, suggesting their modulatory role in the
      optic lobe. Some of PDFMe cells had a hairpin-shaped axonal process running
      toward the lamina then turning back to project into the brain where they
      terminated at various protocerebral areas. The PDFMe cells had a low frequency
      spontaneous spike activity that was higher during the night and was often
      slightly increased by light pulses. Six pairs of PDF-immunoreactive neurons were
      also found in the frontal ganglion. Competitive ELISA with anti-PDF antibodies
      revealed daily cycling of PDF both in the optic lobe and cerebral lobe with an
      increase during the night that persisted in constant darkness. The physiological
      role of PDF is discussed based on these results.

PMID- 18634796
TI  - Effect of 20-hydroxyecdysone and haemolymph on oogenesis in the ixodid tick
      Amblyomma hebraeum.
AB  - Earlier work from our laboratory indicated that injection of 20-hydroxyecdysone
      (20E) into non-vitellogenic female Amblyomma hebraeum ticks stimulates the
      synthesis of vitellogenin (Vg), but not its uptake into oocytes [Friesen, K.,
      Kaufman, W.R., 2004. Effects of 20-hydroxyecdysone and other hormones on egg
      development, and identification of a vitellin-binding protein in the ovary of the
      tick, Amblyomma hebraeum. Journal of Insect Physiology 50, 519-529]. In contrast,
      Thompson et al. [Thompson, D.M., Khalil, S.M.S., Jeffers, L.A.,
      Ananthapadmanaban, U., Sonenshine, D.E., Mitchell, R.D., Osgood, C.J., Apperson,
      C.S., Roe, M.R., 2005. In vivo role of 20-hydroxyecdysone in the regulation of
      the vitellogenin mRNA and egg development in the American dog tick, Dermacentor
      variabilis (Say). Journal of Insect Physiology 51, 1105-1116] demonstrated that
      injection of 20E into virgin female Dermacentor variabilis ticks stimulated both
      vitellogenesis and Vg uptake into oocytes. In addition to the species difference
      in the two studies there were substantially different methods for injecting 20E.
      In our earlier work we injected small partially fed ticks after removing them
      from the host. Thompson et al. injected the females while they remained attached
      to the host. So in this study we repeated our earlier experiments on A. hebraeum
      using on-host injection. We also injected 20E into off-host ticks with or without
      haemolymph collected from engorged ticks (days 2-10 post-engorgement), or from
      large partially fed mated ticks in the rapid phase of engorgement, to see whether
      we might detect a 'vitellogenin uptake factor' (VUF) in haemolymph. Off-host
      injection of 20E (0.45microg/g body weight (bw)) did not induce ovary development
      beyond that of vehicle-injected controls. But ticks in this study, receiving 20E
      plus haemolymph from engorged ticks, showed a significant increase in ovary
      weight beyond that of 20E alone (1.31+/-0.05% bw; 34 for 20E plus haemolymph and
      1.03+/-0.05% bw; 25 for 20E alone). However, in normal engorged A. hebraeum, the
      ovary exceeds 7% bw at the onset of oviposition. As in our earlier work, in this
      study 20E stimulated Vg-synthesis (3.9+/-0.5mgVt-equivalents/ml) beyond that
      occurring in vehicle-injected ticks (0.76+/-0.14mgVt-equivalents/ml), and there
      was a further increase in ticks injected with 20E plus haemolymph from engorged
      ticks (8.9+/-1.0mgVt-equivalents/ml). On-host injection of 20E alone
      (6microg20E/g bw) did not produce a statistically significant increase in oocyte
      length over that of vehicle-injected controls, whereas on-host injection of 20E
      plus engorged haemolymph resulted in significantly larger oocytes (261+/
      57microm) compared to vehicle-injected controls (132+/-11microm), compared to 20E
      alone (131+/-12microm), or haemolymph alone (124+/-24microm). There was a marked
      stimulation of Vg-synthesis by 31microg20E/g bw (6.0+/-1.5mgVt-equivalents/ml)
      compared to vehicle-injected controls (1.02+/-33mgVt-equivalents/ml). Vt
      accumulation by ovaries was significantly greater in ticks treated with
      haemolymph (12+/-3microgVt/mg ovary) or 20E plus haemolymph (56+/-26microgVt/mg
      ovary) compared to vehicle-injected controls (5.1+/-1.5microgVt/mg ovary). There
      was also a significant effect of 6microg20E/g bw plus engorged haemolymph on
      ovary weight (1.74+/-0.29% bw) compared to vehicle-injected ticks (0.95+/-0.10%
      bw), but not compared to ticks injected with 20E alone (1.25+/-0.19% bw). We
      conclude that at least some of the differences observed between the two
      laboratories relate to the species difference, and that there is some evidence
      that the engorged haemolymph of A. hebraeum contains a VUF.

PMID- 18634797
TI  - Juvenile hormone titres and winged offspring production do not correlate in the
      pea aphid, Acyrthosiphon pisum.
AB  - Pea aphids, Acyrthosiphon pisum, reproduce parthenogenetically and are wing
      dimorphic such that offspring can develop into winged (alate) or unwinged
      (apterous) adults. Alate induction is maternal and offspring phenotype is
      entirely determined by changes in the physiology and environment of the mother.
      Juvenile hormones (JHs) have been implicated in playing a role in wing
      differentiation in aphids, however until recently, methods were not available to
      accurately quantify these insect hormones in small insects such as aphids. Using
      a novel LC-MS approach we were able to quantify JH III in pea aphids that were
      either producing a high proportion of winged morphs among their offspring or
      mainly unwinged offspring. We measured JH III titres by pooling the hemolymph of
      12 or fewer individuals (1 microL hemolymph) treated identically. Levels of JH
      ranged from 30 to 163 pg/microL. While aphids in the two treatments strongly
      differed in the proportion of winged morphs among their offspring, their JH III
      titres did not differ significantly. There was also no correlation between JH III
      titre and the proportion of winged offspring in induced aphids. This supports
      earlier findings that wing dimorphism in aphids may be regulated by other
      physiological mechanisms.

PMID- 18634798
TI  - Stink bug interaction with host plants during communication.
AB  - In solitary plant-dwelling stink bug species, success depends crucially on
      efficient mate location and recognition, mediated by signals transmitted through
      the plant. All stink bugs investigated so far communicate with species and sex
      specific narrow-band calling and courtship song signals produced by abdomen
      vibration. Calling songs of lower specificity are characterized by readily
      repeated units emitted with regular repetition rate from the same place on a
      plant, while courtship songs take place at shorter distances in the process of
      species and sex recognition, together with signals of other modalities. Signal
      spectra with about 100Hz fundamental frequency and harmonics below 1000Hz are
      tuned to the resonant properties of their green host plants. The majority of the
      identified leg vibratory receptor cells and the underlying ventral cord
      interneurons respond best in the frequency range below 500Hz. Green plants with
      low pass filtering properties transmit optimally signals with a dominant
      frequency around 100Hz and strongly attenuate vibrations above 600Hz. Accurate
      tuning of signal spectral properties with the plant's mechanical characteristics
      enables communication over several meter distances, with dispersive bending waves
      running through the plant's rod-like structures under standing wave conditions.

PMID- 18634799
TI  - Clonidine effects on protein and carbohydrate electrophysiological responses of
      labellar and tarsal sensilla in Phormia regina.
AB  - The electrophysiological response of labellar and tarsal chemosensilla in the
      blowfly Phormia regina was studied in response to a complex stimulus naturally
      encountered by flies such as sheep faeces, and to beef liver, a proteinaceous
      feeding source. Responses were investigated both before or after injection of
      clonidine, an octopamine agonist previously shown to enhance sucrose ingestion,
      while decreasing that of proteins. As assessed by single sensillum recordings,
      the four different chemosensory - "salt", "sugar", "deterrent" and "water" -
      cells were all activated by both stimuli, regardless of sex and sensillum type,
      the "sugar" one being in all cases the most sensitive to beef liver before
      clonidine injection. Clonidine treatment affected neither labellar nor tarsal
      sensitivity to sucrose. Conversely, clonidine-injected flies showed a significant
      increase in the activity of the "deterrent" cell to beef liver, thus accounting
      for a decrease in protein ingestion. This study for the first time provides
      evidence of a key role of a clonidine-sensitive peripheral taste sensitivity in
      down-regulation of protein ingestion in blowflies. Correlation between peripheral
      sensitivity and behavioural output is discussed.

PMID- 18634800
TI  - Directed expression of dominant-negative p73 enables proliferation of
      cardiomyocytes in mice.
AB  - Previous studies have shown that p53 plays an important role in maintaining cell
      cycle arrest of cardiomyocytes, which might account for the inability of human
      hearts to regenerate adequately after injury. Therefore, inhibition of p53
      represents an attractive strategy to restore cell cycle progression in
      cardiomyocytes although such an approach is hampered by the potential danger of
      concomitant tumor induction. During normal development, N-terminal truncated
      isoforms of the p53-related protein p73 are naturally occurring antagonists of
      p53 and p73, which are not related to tumor induction. We have generated
      recombinant adenoviruses encoding dominant-interfering p73 (Ad-p73DD) to inhibit
      p53/p73 in murine hearts at different developmental stages. We found that the
      expression of p73DD(wt) in newborn mice led to the increase of the relative heart
      weights after 14 days which is paralleled by a significant increase of
      proliferating cardiomyocytes as seen by ICC (BrdU-incorporation, phosphorylation
      of histone3, expression of AuroraB) without induction of apoptosis. Stimulation
      of cell cycle progression in cardiomyocytes went along with a significant down
      regulation of the p53-dependent cdk-inhibitor p21WAF both on mRNA and protein
      level. Furthermore, mRNA levels and protein expression of D-type cyclins and
      cyclins A, B2, and E were selectively increased after expression of p73DD. We
      further show that the cell cycle entry of cardiomyocytes is not restricted to
      neonatal hearts but is also found in adult mouse hearts 5 days after
      intramyocardial injection of Ad-p73DD. Taken together we reason that directed
      expression of dominant-negative p73 might be utilized to stimulate proliferation
      of cardiomyocytes to improve cardiac regeneration.

PMID- 18634801
TI  - Hazard function for cancer patients and cancer cell dynamics.
AB  - The aim of the paper is to develop a procedure for an estimate of an analytical
      form of a hazard function for cancer patients. Although a deterministic approach
      based on cancer cell population dynamics yields the analytical expression, it
      depends on several parameters which should be estimated. On the other hand, a
      kernel estimate is an effective nonparametric method for estimating hazard
      functions. This method provides the pointwise estimate of the hazard function.
      Our procedure consists of two steps: in the first step we find the kernel
      estimate of the hazard function and in the second step the parameters in the
      deterministic model are obtained by the least squares method. A simulation study
      with different types of censorship is carried out and the developed procedure is
      applied to real data.

PMID- 18634802
TI  - Predicting protein structural classes with pseudo amino acid composition: an
      approach using geometric moments of cellular automaton image.
AB  - A novel approach was developed for predicting the structural classes of proteins
      based on their sequences. It was assumed that proteins belonging to the same
      structural class must bear some sort of similar texture on the images generated
      by the cellular automaton evolving rule [Wolfram, S., 1984. Cellular automation
      as models of complexity. Nature 311, 419-424]. Based on this, two geometric
      invariant moment factors derived from the image functions were used as the pseudo
      amino acid components [Chou, K.C., 2001. Prediction of protein cellular
      attributes using pseudo amino acid composition. Proteins: Struct., Funct., Genet.
      (Erratum: ibid., 2001, vol. 44, 60) 43, 246-255] to formulate the protein samples
      for statistical prediction. The success rates thus obtained on a previously
      constructed benchmark dataset are quite promising, implying that the cellular
      automaton image can help to reveal some inherent and subtle features deeply
      hidden in a pile of long and complicated amino acid sequences.

PMID- 18634803
TI  - Projected effects of climate change on tick phenology and fitness of pathogens
      transmitted by the North American tick Ixodes scapularis.
AB  - Ixodes scapularis is the principal tick vector of the Lyme borreliosis agent
      Borrelia burgdorferi and other tick-borne zoonoses in northeastern North America.
      The degree of seasonal synchrony of nymphal and larval ticks may be important in
      influencing the basic reproductive number of the pathogens transmitted by I.
      scapularis. Because the seasonal phenology of tick vectors is partly controlled
      by ambient temperature, climate and climate change could shape the population
      biology of tick-borne pathogens. We used projected monthly normal temperatures,
      obtained from the second version of the Canadian Coupled Global Climate Model
      (CGCM2) under emissions scenario A2 of the Intergovernmental Panel on Climate
      Change for a site in southern Ontario, Canada, to simulate the phenology of I.
      scapularis in a mathematical model. The simulated seasonal abundance of ticks
      then determined transmission of three candidate pathogens amongst a population of
      white-footed mice (Peromyscus leucopus) using a susceptible-infected-recovered
      (SIR) model. Fitness of the different pathogens, in terms of resilience to
      changes in tick and rodent mortality, minima for infection duration, transmission
      efficiency and particularly any additional mortality of rodents specifically
      associated with infection, varied according to the seasonal pattern of immature
      tick activity, which was different under the temperature conditions projected for
      the 2020s, 2050s and 2080s. In each case, pathogens that were long-lived, highly
      transmissible and had little impact on rodent mortality rates were the fittest.
      However, under the seasonal tick activity patterns projected for the 2020s and
      2050s, the fitness of pathogens that are shorter-lived, less efficiently
      transmitted, and more pathogenic to their natural hosts, increased. Therefore,
      climate change may affect the frequency and distribution of I. scapularis-borne
      pathogens and alter their evolutionary trajectories.

PMID- 18634804
TI  - The neural correlate of consciousness?

PMID- 18634805
TI  - Na-Tosyl-Phe chloromethyl ketone prevents granule movement and mast cell
      synergistic degranulation elicited by costimulation of antigen and adenosine.
AB  - Adenosine has been shown to enhance mast cell degranulation when added together
      with an antigen. Such augmentation of mast cell activation is relevant to
      exacerbation of allergic asthma symptoms. Na-Tosyl-Phe chloromethyl ketone (TPCK)
      is a chymotrypsine-like chymase inhibitor, which has anti-inflammatory
      properties. In this study, we investigated the effects of TPCK on mast cell
      synergistic degranulation induced by antigen and adenosine. Here, we report that
      TPCK almost completely suppressed enhanced degranulation by inhibiting granule
      movement. Consistent with this, intraperitoneal administration of TPCK resulted
      in significant amelioration of passive cutaneous anaphylaxis in mice.
      Furthermore, we demonstrated that TPCK completely inhibited Thr308
      phosphorylation of protein kinase B in mast cells stimulated with antigen and
      adenosine. These results provide a novel action of TPCK for the prevention of
      mast cell degranulation induced by antigen and adenosine.

PMID- 18634806
TI  - Differential cocaine-induced modulation of glutamate and dopamine transporters
      after contingent and non-contingent administration.
AB  - Although dopamine and glutamate transmission has been implicated in cocaine
      dependence, the effects of the extinction of cocaine self-administration on
      protein transporters in both of these neurotransmitter systems remain unknown. We
      have used a yoked-box procedure to simultaneously test rats in triads, one rat
      that actively self-administered cocaine (CONT), while the other two received
      yoked injections of either cocaine (NON-CONT) or saline (SALINE). The brains in
      each triad were removed and processed for quantitative autoradiography
      immediately after the last session of cocaine self-administration (Day 0), or
      after 1, 5, or 10 days of extinction, and excitatory amino acid transporters
      (EAATs) and dopamine transporter (DAT) binding was examined. When compared to NON
      CONT and SALINE animals, binding of radioligand to EAATs was significantly lower
      in the hippocampal CA1 field and the cerebellar cortex of CONT rats on Day 0,
      although it was significantly higher after 1 day of extinction in the infralimbic
      cortex. No differences in EAAT binding were observed after 5 or 10 days of
      extinction in any of the brain regions analyzed. In contrast and at all the time
      points of extinction, binding to DAT was significantly enhanced in CONT animals
      when compared to SALINE and NON-CONT rats in different forebrain and
      mesencephalic regions, including the nucleus accumbens, ventral tegmental area or
      caudate putamen. These results suggest that changes in protein transporter
      binding after cocaine self-administration and extinction are transient for EAAT
      while they are more enduring for DAT, and that they depend on the type of access
      to cocaine.

PMID- 18634807
TI  - Serotonin and emotional processing: does it help explain antidepressant drug
      action?
AB  - There is growing interest in the effects of antidepressant drug treatment on
      measures of emotional processing. Such actions may help us understand the role of
      monoamines in emotional dysfunction in depression and how antidepressant drug
      treatments work. Recent studies suggest that decreasing central serotonin
      function with tryptophan depletion can reinstate negative biases in recovered
      depressed patients, even at doses insufficient to induce changes in mood.
      Conversely, antidepressant drug administration increases the processing of
      positive emotional information in healthy volunteers and acutely depressed
      patients early in treatment. This increase in positive bias may provide a
      platform for subsequent cognitive restructuring and learning which contributes to
      the evolution of symptom change in depression. Functional neuroimaging studies
      suggest that these early antidepressant effects involve fronto-limbic and extra
      striate circuitry suggestive of actions on both the initial appraisal and
      attentional processing of affective stimuli. This approach may therefore provide
      a framework for linking psychological and biological processes in emotional
      disorders and their treatment. Antidepressants may not directly modulate mood and
      anxiety but rather allow a different perspective for our ongoing evaluation of
      our self, the world and the future.

PMID- 18634808
TI  - Apomorphine offers new insight into dopaminergic neuron vulnerability in
      mesencephalic cultures.
AB  - The mechanism by which the dopamine neurons of the substantia nigra pars compacta
      degenerate in Parkinson's disease, is partly unknown. Dopamine could be
      implicated in this phenomenon, and in order to explain its toxicity several
      hypotheses have been suggested. The similarity between apomorphine and dopamine
      as regards their chemical, pharmacological and toxicological properties provided
      a basis for investigating the nature of the toxicity of the former agent. In this
      study we describe some effects of apomorphine on mouse mesencephalic cell
      cultures at relatively low concentrations (from 0.5 to 2.5microM), apomorphine
      produced a neurotrophic effect, consisting of a 60% increase in dopaminergic
      neuron survival as measured by [(3)H] dopamine uptake. At high concentrations
      (over 20microM), however, apomorphine induced an increasing cytotoxic effect, as
      measured by the marked decrease in [(3)H] dopamine uptake, and by the direct
      observation of the dopaminergic neurons after TH immunostaining. This study may
      offer a new strategy for investigating the mechanisms underlying DA neuron
      vulnerability.

PMID- 18634809
TI  - Critical role for TARPs in early development despite broad functional redundancy.
AB  - Transmembrane AMPA receptor regulatory proteins (TARPs), including gamma-2, gamma
      3, gamma-4, and gamma-8, are auxiliary subunits for AMPA receptors. Based on
      studies in single knockout mice, it has been suggested that nearly all native
      AMPA receptors are associated with TARPs. To study the interplay between TARP
      family members and AMPA receptors in vivo, we generated mice lacking multiple
      TARPs. Triple knockout mice lacking gamma-3, gamma-4, and gamma-8 are viable and
      fertile, and synaptic AMPA receptor activity is reduced to a level comparable to
      that seen in gamma-8 single knockout mice. In contrast, triple knockout mice
      lacking gamma-2, gamma-3, and either gamma-4 or gamma-8 cannot survive ex utero.
      In particular, gamma-2, gamma-3, gamma-4 triple knockout mice are born apneic and
      paralyzed, despite normal AMPA receptor function in cortical and spinal neurons.
      We found that gamma-8 is expressed at low levels in early postnatal mice and
      regulates AMPA receptor levels at this developmental time period. Thus, the early
      expression of gamma-8 may be responsible for maintaining AMPA receptor functions
      in neonatal neurons. Together, our data indicate that TARPs, in particular gamma
      2, are essential for early development, and that most neurons express multiple
      members of this functionally redundant protein family.

PMID- 18634810
TI  - Serotonin depletion in the dorsal and ventral hippocampus: effects on locomotor
      hyperactivity, prepulse inhibition and learning and memory.
AB  - We present an overview of our studies on the differential role of serotonergic
      projections from the median raphe nucleus (MRN) and dorsal raphe nucleus (DRN) in
      behavioural animal models with relevance to schizophrenia. Stereotaxic
      microinjection of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into
      the MRN or one of its main projections regions, the dorsal hippocampus, induced a
      marked enhancement of phencyclidine-induced locomotor hyperactivity and a
      disruption of prepulse inhibition (PPI) in rats. There was no enhancement of
      locomotor hyperactivity induced by amphetamine or MK-801 or after 5,7-DHT lesions
      of the DRN or ventral hippocampus. Rats with dorsal hippocampus lesions did not
      show significant changes in the Y-maze test for short-term spatial memory, the
      Morris water maze for long-term spatial memory, or in the T-maze delayed
      alternation test for working memory. These chronic lesion studies suggest a
      modulatory influence of serotonergic projections from the MRN to the dorsal
      hippocampus on phencyclidine effects and prepulse inhibition, but not on
      different forms of learning and memory. The results provide new insight into the
      role of serotonin in the dorsal hippocampus in aspects of schizophrenia.

PMID- 18634811
TI  - Effects of fentanyl dose and exposure duration on the affective and somatic signs
      of fentanyl withdrawal in rats.
AB  - Fentanyl is a potent mu-opioid receptor agonist that is widely used for the
      treatment of chronic pain. The aim of the present study was to investigate the
      effect of the dose of fentanyl and the exposure duration on the affective and
      somatic signs of fentanyl withdrawal in rats. Fentanyl and saline were
      chronically administered via osmotic minipumps. A discrete-trial intracranial
      self-stimulation procedure was used to provide a measure of brain reward function
      and somatic signs were recorded from a checklist of opioid abstinence signs. The
      opioid receptor antagonist naloxone elevated the brain reward thresholds of the
      rats chronically treated with high doses of fentanyl (0.3 and 0.6mg/kg/day), but
      not those of rats treated with low doses of fentanyl (0.006 and 0.06mg/kg/day).
      Fentanyl had a dose-dependent effect on the naloxone-induced elevations in brain
      reward thresholds. On a similar note, the discontinuation of the administration
      of high doses of fentanyl was associated with elevations in brain reward
      thresholds and the discontinuation of the administration of low doses of fentanyl
      did not lead to an elevation in brain reward thresholds. The results also
      demonstrated that the duration of fentanyl administration does not affect
      naloxone-induced elevation in brain reward thresholds. In contrast, the somatic
      withdrawal syndrome gradually developed over time; maximum somatic signs were
      observed 120h after pump implantation. These studies suggest that the magnitude
      and duration of the negative affective signs of fentanyl withdrawal depend on the
      dose of fentanyl administered and not on the duration of fentanyl administration.

PMID- 18634812
TI  - Cannabidiol prevents a post-ischemic injury progressively induced by cerebral
      ischemia via a high-mobility group box1-inhibiting mechanism.
AB  - We examined the cerebroprotective mechanism of cannabidiol, the non-psychoactive
      component of marijuana, against infarction in a 4-h mouse middle cerebral artery
      (MCA) occlusion model. Cannabidiol was intraperitoneally administrated
      immediately before and 3h after cerebral ischemia. Infarct size and
      myeloperoxidase (MPO) activity, a marker of neutrophil, monocyte/macropharge,
      were measured at 24h after cerebral ischemia. Activated microglia and astrocytes
      were evaluated by immunostaining. Moreover, high-mobility group box1 (HMGB1) was
      also evaluated at 1 and 3 days after MCA occlusion. In addition, neurological
      score and motor coordination on the rota-rod test were assessed at 1 and 3 days
      after cerebral ischemia. Cannabidiol significantly prevented infarction and MPO
      activity at 20h after reperfusion. These effects of cannabidiol were not
      inhibited by either SR141716 or AM630. Cannabidiol inhibited the MPO-positive
      cells expressing HMGB1 and also decreased the expression level of HMGB1 in
      plasma. In addition, cannabidiol decreased the number of Iba1- and GFAP-positive
      cells at 3 days after cerebral ischemia. Moreover, cannabidiol improved
      neurological score and motor coordination on the rota-rod test. Our results
      suggest that cannabidiol inhibits monocyte/macropharge expressing HMGB1 followed
      by preventing glial activation and neurological impairment induced by cerebral
      ischemia. Cannabidiol will open new therapeutic possibilities for post-ischemic
      injury via HMGB1-inhibiting mechanism.

PMID- 18634813
TI  - Working memory impairment and reduced hippocampal and prefrontal cortex c-Fos
      expression in a rat model of cirrhosis.
AB  - Hepatic encephalopathy (HE) is a frequent neurological complication observed in
      patients with liver malfunction. Previous studies have shown memory impairment in
      these patients. In order to investigate brain substrates of spatial working
      memory impairment in chronic HE, neuronal expression of c-Fos protein was studied
      in an experimental model of cirrhosis. Control and cirrhotic rats were trained on
      a spatial working memory task in the Morris water maze (MWM). Differences between
      groups were found in the working memory task. Cirrhotic rats were unable to
      locate the platform in the retention trial. Neuronal activation, measured by c
      Fos protein, was compared between groups. No differences were found in c-Fos
      expression of control and cirrhotic rats that were not tested in the MWM. Working
      memory task produced increase in c-Fos positive cells in dorsal hippocampus, CA1
      and CA3, and prefrontal cortex in control group compared to thioacetamide group
      or naive, which only swam in the maze during a similar time. These findings
      suggest that cirrhotic rats show spatial working memory impairment that could be
      linked to dysfunction in neuronal activity in prefrontal cortex and hippocampus.

PMID- 18634814
TI  - Effects of endocrine disruptors on genes associated with 17beta-estradiol
      metabolism and excretion.
AB  - In order to provide a global analysis of the effects of endocrine disruptors on
      the hormone cellular bioavailability, we combined 17beta-estradiol (E2) cellular
      flow studies with real-time PCR and Western blot expression measurements of genes
      involved in the hormone metabolism and excretion. Three endocrine disruptors
      commonly found in food were chosen for this study, which was conducted in the
      estrogen receptor (ER) negative hepatoblastoma HepG2 cell line: bisphenol A
      (BPA), genistein (GEN) and resveratrol (RES). We showed that 24 h after a single
      dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP
      binding cassette transporters (the multidrug resistance or MDR, and the multidrug
      resistance associated proteins or MRP) uridine diphosphate
      glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta
      estradiol elimination process were significantly modulated and that 17beta
      estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3
      expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced
      17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1
      expressions, and led to 17beta-estradiol cellular retention. Thus, we demonstrate
      that bisphenol A, genistein and resveratrol modulate 17beta-estradiol cellular
      bioavailability in HepG2 and that these modulations most probably involve
      regulations of 17beta-estradiol phase II and III metabolism proteins. Up to now,
      the estrogenicity of environmental estrogenic pollutants has been based on the
      property of these compounds to bind to ERs. Our results obtained with ER negative
      cells provide strong evidence for the existence of ER-independent pathways
      leading to endocrine disruption.

PMID- 18634815
TI  - To what extent does genealogical ancestry imply genetic ancestry?
AB  - Recent statistical and computational analyses have shown that a genealogical most
      recent common ancestor (MRCA) may have lived in the recent past [Chang, J.T.,
      1999. Recent common ancestors of all present-day individuals. Adv. Appl. Probab.
      31, 1002-1026. 1027-1038; Rohde, D.L.T., Olson, S., Chang, J.T., 2004. Modelling
      the recent common ancestry of all living humans. Nature 431, 562-566]. However,
      coalescent-based approaches show that genetic most recent common ancestors for a
      given non-recombining locus are typically much more ancient [Kingman, J.F.C.,
      1982a. The coalescent. Stochastic Process Appl. 13, 235-248; Kingman, J.F.C.,
      1982b. On the genealogy of large populations. J. Appl. Probab. 19A, 27-43]. It is
      not immediately clear how these two perspectives interact. This paper
      investigates relationships between the number of descendant alleles of an
      ancestor allele and the number of genealogical descendants of the individual who
      possessed that allele for a simple diploid genetic model extending the
      genealogical model of [Chang, J.T., 1999. Recent common ancestors of all present
      day individuals. Adv. Appl. Probab. 31, 1002-1026. 1027-1038].

PMID- 18634816
TI  - Novel function of glutathione transferase in rat liver mitochondrial membrane:
      role for cytochrome c release from mitochondria.
AB  - Microsomal glutathione transferase (MGST1) is activated by oxidative stress.
      Although MGST1 is found in mitochondrial membranes (mtMGST1), there is no
      information about the oxidative activation of mtMGST1. In the present study, we
      aimed to determine whether mtMGST1 also undergoes activation and about its
      function. When rats were treated with galactosamine/lipopolysaccharide
      (GalN/LPS), mtMGST1 activity was significantly increased, and the increased
      activity was reduced by the disulfide reducing agent dithiothreitol. In
      mitochondria from GalN/LPS-treated rats, disulfide-linked mtMGST1 dimer and mixed
      protein glutathione disulfides (glutathionylation) were detected. In addition,
      cytochrome c release from mitochondria isolated from GalN/LPS-treated rats was
      observed, and the release was inhibited by anti-MGST1 antibodies. Incubation of
      mitochondria from control rats with diamide and diamide plus GSH in vitro
      resulted in dimer- and mixed disulfide bond-mediated activation of mtMGST1,
      respectively. The activation of mtMGST1 by diamide plus GSH caused cytochrome c
      release from the mitochondria, and the release was prevented by treatment with
      anti-MGST1 antibodies. In addition, diamide plus GSH treatment caused
      mitochondrial swelling accompanied by cytochrome c release, which was inhibited
      by cyclosporin A (CsA) and bongkrekic acid (BKA), inhibitors of the mitochondrial
      permeability transition (MPT) pore. Furthermore, mtMGST1 activity was also
      inhibited by CsA and BKA. These results indicate that mtMGST1 is activated
      through mixed disulfide bond formation that contributes to cytochrome c release
      from mitochondria through the MPT pore.

PMID- 18634817
TI  - Progeric effects of catalase inactivation in human cells.
AB  - Peroxisomes generate hydrogen peroxide, a reactive oxygen species, as part of
      their normal metabolism. A number of pathological situations exist in which the
      organelle's capacity to degrade the potentially toxic oxidant is compromised. It
      is the peroxidase, catalase, which largely determines the functional antioxidant
      capacity of the organelle, and it is this enzyme that is affected in aging, in
      certain diseases, and in response to exposure to specific chemical agents. To
      more tightly control the enzymatic activity of peroxisomal catalase and carefully
      document the effects of its impaired action on human cells, we employed the
      inhibitor 3-amino-1,2,4-triazole. We show that by chronically reducing catalase
      activity to approximately 38% of normal, cells respond in a dramatic manner,
      displaying a cascade of accelerated aging reactions. Hydrogen peroxide and
      related reactive oxygen species are produced, protein and DNA are oxidatively
      damaged, import into peroxisomes and organelle biogenesis is corrupted, and
      matrix metalloproteinases are hyper-secreted from cells. In addition,
      mitochondria are functionally impaired, losing their ability to maintain a
      membrane potential and synthesize reactive oxygen species themselves. These
      latter results suggest an important redox-regulated connection between the two
      organelle systems, a topic of considerable interest for future study.

PMID- 18634818
TI  - Relative mislocalization of successively presented stimuli.
AB  - When observers were asked to localize the peripheral position of a briefly
      presented target with respect to a previously presented comparison stimulus, they
      tended to judge the target as being more towards the fovea than the comparison
      stimulus. Three experiments revealed that the mislocalization only emerged when
      the comparison stimulus and the target were presented successively. Varying the
      temporal interval between stimuli showed that the mislocalization reversed with
      longer stimulus-onset asynchronies. Further, the mislocalization was increased
      with a decrease of the spatial distance between stimuli. These findings suggested
      that the mislocalization originated from local excitatory and inhibitory
      mechanisms. Corroborating this idea a neuronal dynamic field model was
      successfully developed to account for the findings.

PMID- 18634820
TI  - Identification and expression profile of gene transcripts differentially
      expressed during metallic exposure in Eisenia fetida coelomocytes.
AB  - The aim of this work was to identify in Eisenia fetida genes whose expression are
      regulated following exposure to a complex mixture of metallic trace elements
      (MTE) representative of a highly polluted smelter soil. Suppression subtractive
      hybridization (SSH) was used to construct cDNA libraries enriched in up- or down
      regulated transcripts in the immune-circulating cells of the coelomic cavities,
      namely coelomocytes, from worms exposed to metallic pollution. Among 1536 SSH
      derived cDNA clones sequenced, we identified 764 unique ESTs of which we selected
      18 candidates on the basis of their redundancy. These selected candidates were
      subjected to a two-step validation procedure based on the study of their
      expression level by real-time PCR. The first step consisted in measuring the
      expression of the 18 candidates in worms exposed to artificial contaminated soil.
      The second step consisted in measuring the expression in animals exposed to a
      "naturally" contaminated soil sampled close to a smelter. Both steps allowed us
      to highlight 3 candidates that are strongly induced in worms exposed to a smelter
      polluted soil. These candidates are: the well-known MTE-induced Cd
      metallothionein and 2 original biomarkers, lysenin, and a transcript, which
      cloning of the complete coding sequence identified as the coactosin-like protein.

PMID- 18634819
TI  - Genes regulated by caloric restriction have unique roles within transcriptional
      networks.
AB  - Caloric restriction (CR) has received much interest as an intervention that
      delays age-related disease and increases lifespan. Whole-genome microarrays have
      been used to identify specific genes underlying these effects, and in mice, this
      has led to the identification of genes with expression responses to CR that are
      shared across multiple tissue types. Such CR-regulated genes represent strong
      candidates for future investigation, but have been understood only as a list,
      without regard to their broader role within transcriptional networks. In this
      study, co-expression and network properties of CR-regulated genes were
      investigated using data generated by more than 600 Affymetrix microarrays. This
      analysis identified groups of co-expressed genes and regulatory factors
      associated with the mammalian CR response, and uncovered surprising network
      properties of CR-regulated genes. Genes downregulated by CR were highly connected
      and located in dense network regions. In contrast, CR-upregulated genes were
      weakly connected and positioned in sparse network regions. Some network
      properties were mirrored by CR-regulated genes from invertebrate models,
      suggesting an evolutionary basis for the observed patterns. These findings
      contribute to a systems-level picture of how CR influences transcription within
      mammalian cells, and point towards a comprehensive understanding of CR in terms
      of its influence on biological networks.

PMID- 18634821
TI  - Complete nucleotide sequence of plasmid plca36 isolated from Lactobacillus casei
      Zhang.
AB  - The complete 36,487 bp sequence of plasmid plca36 from Lactobacillus casei Zhang
      was determined. Plca36 contains 44 predicted coding regions, and to 23 of them
      functions could be assigned. For the first time, we identified a relBE toxin
      antitoxin (TA) locus in a Lactobacillus genus, perhaps indicating a potential
      role for plca36 in host survival under extreme nutritional stress. A region
      encoding a cluster of conjugation genes (tra) was also identified. The cluster
      showed high similarity and co-linearity with tra regions of pWCFS103 and pMRC01
      from Lactobacillus plantarum and Lactococcus lactis, respectively. Comparative
      gene analysis revealed that plasmids from the genus Lactobacillus may have
      contributed to the environmental adaptation mainly by providing carbohydrate and
      amino acid transporters. In addition, two chromosome-encoded relBE systems in
      Lactobacillus johnsonii and Lactobacillus gasseri were identified.

PMID- 18634822
TI  - Optical monitoring of neuronal activity at high frame rate with a digital random
      access multiphoton (RAMP) microscope.
AB  - Two-photon microscopy offers the promise of monitoring brain activity at multiple
      locations within intact tissue. However, serial sampling of voxels has been
      difficult to reconcile with millisecond timescales characteristic of neuronal
      activity. This is due to the conflicting constraints of scanning speed and signal
      amplitude. The recent use of acousto-optic deflector scanning to implement random
      access multiphoton microscopy (RAMP) potentially allows to preserve long
      illumination dwell times while sampling multiple points-of-interest at high
      rates. However, the real-life abilities of RAMP microscopy regarding sensitivity
      and phototoxicity issues, which have so far impeded prolonged optical recordings
      at high frame rates, have not been assessed. Here, we describe the design,
      implementation and characterisation of an optimised RAMP microscope. We
      demonstrate the application of the microscope by monitoring calcium transients in
      Purkinje cells and cortical pyramidal cell dendrites and spines. We quantify the
      illumination constraints imposed by phototoxicity and show that stable continuous
      high-rate recordings can be obtained. During these recordings the fluorescence
      signal is large enough to detect spikes with a temporal resolution limited only
      by the calcium dye dynamics, improving upon previous techniques by at least an
      order of magnitude.

PMID- 18634823
TI  - Using the CatWalk method to assess weight-bearing and pain behaviour in walking
      rats with ankle joint monoarthritis induced by carrageenan: effects of morphine
      and rofecoxib.
AB  - The CatWalk automated quantitative gait analysis technique has been validated as
      a method to quantify behaviour in rodent models of neuropathic and arthritic
      pain. Its suitability for pharmacological testing of pain relief has been
      questioned, however, based on findings using paw soft tissue plantar inflammation
      as stimulus. In this study, we investigated the effectiveness of morphine and
      rofecoxib in reducing pain behaviour in monoarthritic rats. The CatWalk was used
      to assess print area, weight load and duration of stance for each paw, as well as
      interlimb coordination, before and 3, 5 and 24h after injection of lambda
      carrageenan into one ankle joint. The monoarthritic rat showed a reduced print
      area, weight load and duration of stance for the injected paw at all times
      tested, and a significant loss of interlimb coordination at 3 and 5h after
      injection. Both morphine (3.75 and 15 micromol/kg s.c.) and rofecoxib (7.5 and 30
      micromol/kg p.o.) reduced the effects of carrageenan. In conclusion, behavioural
      effects interpreted as reflecting movement-related pain in monoarthritic rats and
      pharmacological treatment of the monoarthritis can objectively and efficiently be
      quantified in detail by the CatWalk method.

PMID- 18634824
TI  - Effectiveness of a new modified intraluminal suture for temporary middle cerebral
      artery occlusion in rats of various weight.
AB  - Intraluminal temporary middle cerebral artery occlusion (MCAO) is a common model
      of ischemic stroke in the rat with significant, suture and weight-dependent
      variability along with increased risk of subarachnoid haemorrhage (SAH). Our
      purpose was to increase reproducibility and decrease SAH using a modification of
      the Koizumi suture. We compared a Koizumi 5/0 Ethilon poly-l-lysine-coated suture
      (s-2, group B) to an identical, uncoated one (s-1, group A) and the Belayev's 3/0
      suture (s-3, group C), in the 2-h MCAO model in Wistar rats of varying weight
      (310-527 g). Assessment included successful infarction rates, the modified
      neurological stroke scale (mNSS), a modified Bederson's scale (mBS), the grid
      walking test (GWT), infarction volume (with rostrocaudal subanalysis and analysis
      of cortical/striatal involvement) and hemispheric edema. The s-2 suture increased
      the successful MCAO from 61.1% and 66.6% (groups A and C) to 97.5% in group B and
      induced a more severe clinical stroke (P<0.05) irrespective of animal's weight,
      with no incidence of SAH. Infarction volume and ipsilateral hemispheric edema
      significantly (P<0.05) increased and well correlated with the mNSS (P<or=0.005),
      the mBS (P<or=0.01) and GWT outcomes. Our data suggest that the new modified
      suture induces a more reproducible ischemic stroke in Wistar rats for temporary
      MCAO experiments, overcoming the variability of weight and the risk of SAH.

PMID- 18634825
TI  - Characterization of oligomers induced by inverse agonists of CTLA-4.
AB  - Although cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibits T cell
      activation when ligated by B7 molecules on antigen-presenting cells, it can also
      act as an activating receptor when binding certain soluble recombinant ligands
      known as inverse agonists. Following ligation with an inverse agonist, we
      observed CTLA-4 microclusters evenly distributed on the T cell surface over a 60
      min period. We have previously shown that the inverse agonist properties of these
      ligands correlate with their capacity to induce the formation of large CTLA-4
      oligomers that are distinctly different from those resulting by CTLA-4 engagement
      with membrane-bound B7. These oligomers are composed of CTLA-4 molecules
      expressed on the cell surface and decrease from both the soluble cell lysate and
      lipid rafts upon cellular fractionation. Formation of these inverse agonist
      induced CTLA-4 oligomers does not require an intact actin cytoskeleton. However,
      modulation of these oligomers was partially blocked upon actin depolymerization.
      Retention of CTLA-4 oligomers on the cell surface correlated with enhanced T cell
      signaling. Together, our data further characterize the structural basis of
      inverse agonist properties for CTLA-4 ligands that may be used in the design and
      screening of therapeutic biologicals targeting this receptor.

PMID- 18634826
TI  - Modulation of desmoglein-3-specific T cell response and pathogenic antibody
      generation in mice.
AB  - Pemphigus is a severe blistering disease of the skin and mucous membranes caused
      by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein-3 (Dsg3)
      and desmoglein-1 (Dsg1). The antibody titer and the distinct isotype patterns
      correlated with the disease activity. To identify their functional properties and
      pathogenic potential, we immunized C57BL/6 and Balb/c mice with recombinant Dsg3
      fusion protein plus complete Freund's adjuvant (CFA) or Aluminum Hydroxide
      hydrate (Alum). After immunization, the cytokine profiles on T cells, the
      antibody titers, and the isotypes were analyzed. The pathogenicity of different
      autoantibody isotypes was evaluated by antibody passive transfer approach. It was
      found that Th1 type cytokine interferon gamma (IFN gamma) was elevated in the CFA
      treated group, while Th2 type cytokine interleukin-4 (IL-4) was increased in the
      Alum-treated group. IgG1 expression was persistent in the Alum group while IgG2a
      was predominant in the CFA group. Neonatal mice transferred with sera from the
      Alum group, but not the CFA group, developed skin lesions clinically and
      histologically with IgG deposition on the epidermal keratinocytes. Our findings
      suggest that distinct T cell responses could be switched after active
      immunization combined with different adjuvants, resulting in distinct anti-Dsg3
      antibody isotypes with different pathogenic activities in disease development.
      These findings shed new light on the immunopathogenesis of PV and offer a new
      therapeutic strategy for this potentially fatal disorder.

PMID- 18634827
TI  - Multiplexed molecular assay for rapid exclusion of foot-and-mouth disease.
AB  - A nucleic acid-based multiplexed assay was developed that combines detection of
      foot-and-mouth disease virus (FMDV) with rule-out assays for two other foreign
      animal diseases and four domestic animal diseases that cause vesicular or
      ulcerative lesions indistinguishable from FMDV infection in cattle, sheep and
      swine. The FMDV "look-alike" diagnostic assay panel contains 5 PCR and 12 reverse
      transcriptase PCR (RT-PCR) signatures for a total of 17 simultaneous PCR
      amplifications for 7 diseases plus incorporating 4 internal assay controls. It
      was developed and optimized to amplify both DNA and RNA viruses simultaneously in
      a single tube and employs Luminex liquid array technology. Assay development
      including selection of appropriate controls, a comparison of signature
      performance in single and multiplex testing against target nucleic acids, as well
      of limits of detection for each of the individual signatures is presented. While
      this assay is a prototype and by no means a comprehensive test for FMDV "look
      alike" viruses, an assay of this type is envisioned to have benefit to a
      laboratory network in routine surveillance and possibly for post-outbreak proof
      of freedom from foot-and-mouth disease.

PMID- 18634828
TI  - Increased sensitivity for detecting avian influenza-specific antibodies by a
      modified hemagglutination inhibition assay using horse erythrocytes.
AB  - The hemagglutination inhibition (HI) assay is a widely used serological method to
      measure the levels of protective antibody responses against influenza viruses.
      However, the traditional HI assay which uses chicken erythrocytes is not
      sufficiently sensitive for detecting HI antibodies specific to avian influenza
      viruses. Previously, it was demonstrated that employing an assay using horse
      erythrocytes was able to increase the sensitivity of HI assay. The current report
      describes further optimization of this modified HI assay. It was shown that this
      method was able to increase detection of HI activities in rabbit sera immunized
      with H5 HA antigens, and proved that this increased sensitivity is useful in
      dissecting the strain specificity of HI antibody responses. In addition, the
      modified HI assay using horse erythrocytes increased the sensitivity of detecting
      HI antibodies specific for three major serotypes of avian influenza viruses, H5,
      H7 and H9, in people who may have asymptomatic infection with avian influenza
      viruses. Based on these results, the optimized use of horse erythrocytes should
      be standard practice for detecting HI activities against avian influenza viruses.

PMID- 18634829
TI  - Identification and mapping of a region on the mRNA of Morbillivirus nucleoprotein
      susceptible to RNA interference.
AB  - The morbillivirus genus includes important pathogens such as measles virus (MV),
      peste des petits ruminants virus (PPRV), and rinderpest virus (RPV) and forms a
      group of antigenically related viruses. The viral nucleoprotein (N) is a well
      conserved protein among the genus and plays a central role in the replication of
      the virus. Using a comprehensive approach for siRNA screening of the conserved
      sequences of the N gene, including sequence analysis and functional in vitro
      tests, we have identified a region for the design of siRNA effective for the
      control of PPRV, RPV, and MV replication. Silencing of the N mRNA efficiently
      shuts down the production of N transcripts, the expression of N protein, and the
      indirect inhibition of matrix protein, resulting in the inhibition of PPRV
      progeny by 10,000-fold. These results suggest that siRNA against this region
      should be further explored as a therapeutic strategy for morbillivirus
      infections.

PMID- 18634830
TI  - Chronic corticosterone administration does not potentiate unconditioned freezing
      to the predator odor, trimethylthiazoline.
AB  - Chronic high levels of corticosterone (CORT) are known to facilitate learning and
      memory of aversive events. Whether this effect of chronic CORT also generalizes
      to unconditioned or unlearned fear behavior is not known. The present study
      investigated whether high levels of chronic CORT enhance unconditioned fear to a
      predator odor, trimethylthiazoline (TMT), an innate fear stimulus to rodents. TMT
      induces a dose-related freezing response, a prototypical behavior to fearful
      stimuli, in rats. The first experiment demonstrated that dose-related freezing to
      repeated exposures of TMT does not habituate, sensitize or produce contextually
      conditioned fear, and therefore can be used to measure the effects of chronic
      CORT on unconditioned fear to repeated exposures of TMT. In Experiment 2, 21-day
      release corticosterone pellets (200mg) were implanted subcutaneously in male,
      Sprague-Dawley rats. Control rats received sham implantation. On days when TMT
      was not present, chronic CORT rats froze significantly more than sham rats.
      However, while TMT-induced freezing in both chronic CORT and sham rats, freezing
      during exposure to TMT was not further enhanced in chronic CORT rats. Thus,
      chronic CORT appears to increase fear as measured by freezing, possibly by
      enhancing vigilance, but does not facilitate fear behavior induced by the innate
      fear stimulus, TMT.

PMID- 18634831
TI  - Neonatal endotoxin exposure impairs avoidance learning and attenuates endotoxin
      induced sickness behavior and central IL-1beta gene transcription in adulthood.
AB  - Infection during infancy, a time of critical neural development, may have long
      term implications. Infection or exposure to an immune stimulus such as
      lipopolysaccharide (LPS) early in life leads to alterations in the reactivity of
      the hypothalamic-pituitary-adrenal axis (HPA) and febrile response in adulthood.
      Relatively few studies have assessed the behavioral and cognitive alterations
      induced by perinatal immune challenge. The data indicate that neonatal immune
      activation may alter adulthood behavior with, or sometimes without, subsequent
      adulthood exposure, depending on the study. The current study investigated the
      behavioral effects and IL-1beta transcription following intraperitoneal LPS
      administration on postnatal days (PNDs) 4 and 5, and subsequent LPS or saline
      administration in adulthood. Alterations in anxiety, motor behavior, and learning
      were assessed in male and female subjects. The results indicate that neonatal
      endotoxin exposure attenuated the LPS-induced decrease in motor behavior in
      female, but not male, subjects. Furthermore, perinatal immune activation
      disrupted avoidance learning in male, but not female, subjects in the absence of
      adulthood LPS administration. In addition, for male subjects, neonatal LPS
      exposure diminished central IL-1beta gene transcription following adulthood LPS
      administration. These findings indicate that perinatal endotoxin exposure may
      lead to alterations in the behavioral response to adulthood LPS administration,
      and provide evidence that early immune activation alone may trigger alterations
      in adulthood learning ability.

PMID- 18634832
TI  - Attenuation of morphine withdrawal signs by a GABAB receptor agonist in the locus
      coeruleus of rats.
AB  - In the present study, the effects of intra-locus coeruleus (LC) injection of
      GABA(B) receptor-interacting agents on naloxone-induced withdrawal signs of
      morphine-dependent rats were examined. The GABA(B) receptor agonist and
      antagonists were injected 5 min prior to naloxone injection. Baclofen, a GABA(B)
      receptor agonist, decreased the TWS in a dose-dependent manner but CGP35348, a
      GABA(B) receptor antagonist, alone had no effect. On the other hand, baclofen
      effects were reversed by CGP35348. It may be concluded that activation of GABA(B)
      receptor mechanisms in the LC reduces precipitated withdrawal symptoms from
      chronic morphine treatment.

PMID- 18634833
TI  - Phosphorylation, lipid raft interaction and traffic of alpha-synuclein in a yeast
      model for Parkinson.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by the
      formation of Lewy bodies containing aggregated alpha-synuclein. We used a yeast
      model to screen for deletion mutants with mislocalization and enhanced inclusion
      formation of alpha-synuclein. Many of the mutants were affected in functions
      related to vesicular traffic but especially mutants in endocytosis and vacuolar
      degradation combined inclusion formation with enhanced alpha-synuclein-mediated
      toxicity. The screening also allowed for identification of casein kinases
      responsible for alpha-synuclein phosphorylation at the plasma membrane as well as
      transacetylases that modulate the alpha-synuclein membrane interaction. In
      addition, alpha-synuclein was found to associate with lipid rafts, a phenomenon
      dependent on the ergosterol content. Together, our data suggest that toxicity of
      alpha-synuclein in yeast is at least in part associated with endocytosis of the
      protein, vesicular recycling back to the plasma membrane and vacuolar fusion
      defects, each contributing to the obstruction of different vesicular trafficking
      routes.

PMID- 18634834
TI  - FRET with multiply labeled HERG K(+) channels as a reporter of the in vivo coarse
      architecture of the cytoplasmic domains.
AB  - The intracellular N-terminus of human ether-a-go-go-related gene (HERG) potassium
      channels constitutes a key determinant of activation and deactivation
      characteristics and is necessary for hormone-induced modifications of gating
      properties. However, the general organization of the long amino and carboxy HERG
      terminals remains unknown. In this study we performed fluorescence resonance
      energy transfer (FRET) microscopy with a library of fluorescent HERG fusion
      proteins obtained combining site-directed and transposon-based random insertion
      of GFP variants into multiple sites of HERG. Determinations of FRET efficiencies
      with functional HERG channels labeled in different combinations localize the
      fluorophores, introduced in the amino and carboxy ends, in two quadratic planes
      of 7.8 and 8.6 nm lateral size, showing a vertical separation of nearly 8 nm
      without major angular torsion between the planes. Similar analysis using labels
      at positions 345 and 905 of the amino and carboxy terminals, located them
      slightly above the planes delimited by the amino and carboxy end labels,
      respectively. Our data also indicate an almost vertical arrangement of the
      fluorophores introduced in the NH(2) and COOH ends and at position 905, but a
      near 45 degrees angular rotation between the planes delimited by these labels and
      the 345-located fluorophores. Systematic triangulation using interfluorophore
      distances coming from multiply labeled channels provides an initial constraint on
      the overall in vivo arrangement of the HERG cytoplasmic domains, suggesting that
      the C-linker/CNBD region of HERG hangs centrally below the transmembrane core,
      with the initial portion of the amino terminus around its top and side surfaces
      directed towards the gating machinery.

PMID- 18634836
TI  - Genome research in the light of ultrafast sequencing technologies.

PMID- 18634835
TI  - Embryonic stem cell-derived neural precursor cells improve memory dysfunction in
      Abeta(1-40) injured rats.
AB  - The versatility of neural precursor cells (NPCs) derived from mouse embryonic
      stem cells (ESCs) has recently rekindled interests in cell replacement strategies
      aimed at neurodegenerative diseases. We observed the survival, migration,
      differentiation and functional recovery of NPCs transplanted into the hippocampus
      of aggregated beta-amyloid (Abeta) peptide injured rats. Congo Red plaques, Fluro
      jade B positive degenerating neurons and neuronal loss were observed in the Abeta
      injured hippocampus of rats, accompanied with significant increases in escape
      latency and decrease in the ratio of exploratory time in a Morris water maze
      test. EGFP-expressing mouse ES cells were induced into Nestin-positive NPCs
      before transplantation into the Abeta-injured hippocampus. A marked decrease in
      escape latency and exploratory time were observed at least 16 weeks after
      transplantation compared to Abeta-injured animals without grafts. Grafted EGFP
      expressing NPCs spread away from the injection tract and about 12.01+/-0.67% and
      9.41+/-0.78% of NPCs differentiated into, respectively, GFAP- and NF200-positive
      cells 4 W after transplantation. These ratios gradually increased to 40.25+/
      0.57% and 19.35+/-0.84% by 16 W. The restoration of hippocampal function by ESCs
      suggests that cell transplantation may be the effective choice to improve the
      cognitive function caused by Abeta injured.

PMID- 18634837
TI  - Random mutagenesis of a recombinant microbial transglutaminase for the generation
      of thermostable and heat-sensitive variants.
AB  - Recombinant microbial transglutaminase (rMTG), an enzyme useful for the cross
      linking or the posttranslational modification of (therapeutic) proteins, was
      optimized by random mutagenesis for the first time. A screening method was
      developed which, in addition to state-of-the-art procedures, includes a
      proteolytic activation step of the expressed soluble pro-enzyme. The library of
      5,500 clones was screened for variants with increased thermostability and heat
      sensitivity, respectively. Mutant enzymes were overproduced, isolated and
      characterized. After just one round of mutagenesis, nine variants with a single
      amino acid exchange showed a remarkably increased thermostability at 60 degrees
      C. The exchange of a serine residue close to the N-terminus against proline
      resulted in an rMTG mutant (S2P) with 270% increased half-life. Seven variants
      exhibited an increased heat-sensitivity at 60 degrees C of which one mutant
      (G25S) retained its specific activity between 10 and 40 degrees C. The mutations
      responsible for the increased thermostability and the heat-sensitivity were
      identified and assigned to the three-dimensional (3D) structure. All single point
      mutations related to changed thermal properties of rMTG are located in the N
      terminal domain (i.e. the left side wall of the active site cleft of the front
      view of the MTG as defined by the literature [Kashiwagi, T., Yokoyama, K.,
      Ishikawa, K., Ono, K., Ejima, D., Matsui, H., Suzuki, E., 2002. Crystal structure
      of microbial transglutaminase from Streptoverticillium mobaraense. J. Biol. Chem.
      277, 44252-44260] showing the importance of this part of the protein.

PMID- 18634838
TI  - Preface. Fifth International Nanomedicine and Drug Delivery Symposium
      (NanoDDS'07).

PMID- 18634840
TI  - From Claude Bernard to Walter Cannon. Emergence of the concept of homeostasis.
AB  - Roots of current conceptions of the regulation of states of the body through
      negative feedback mechanisms are traced back to Bernard's ideas on active
      stabilisation of bodily states against disturbances from the outside, revived by
      Henderson and Haldane, and crystallised in Cannon's concept of homeostasis.

PMID- 18634839
TI  - Gene transfer to hemophilia A mice via oral delivery of FVIII-chitosan
      nanoparticles.
AB  - Effective oral delivery of a non-viral gene carrier would represent a novel and
      attractive strategy for therapeutic gene transfer. To evaluate the potential of
      this approach, we studied the oral gene delivery efficacy of DNA polyplexes
      composed of chitosan and Factor VIII DNA. Transgene DNA was detected in both
      local and systemic tissues following oral administration of the chitosan
      nanoparticles to hemophilia A mice. Functional factor VIII protein was detected
      in plasma by chromogenic and thrombin generation assays, reaching a peak level of
      2-4% FVIII at day 22 after delivery. In addition, a bleeding challenge one month
      after DNA administration resulted in phenotypic correction in 13/20 mice given
      250-600 microg of FVIII DNA in chitosan nanoparticles, compared to 1/13 mice
      given naked FVIII DNA and 0/6 untreated mice. While further optimization would be
      required to render this type of delivery system practical for hemophilia A gene
      therapy, the findings suggest the feasibility of oral, non-viral delivery for
      gene medicine applications.

PMID- 18634841
TI  - KiSS-1/kisspeptins and the metabolic control of reproduction: physiologic roles
      and putative physiopathological implications.
AB  - It is well established that reproductive function is gated by the state of energy
      reserves of the organism; conditions of metabolic stress and energy insufficiency
      being frequently coupled to disturbed reproductive maturation and/or infertility.
      In addition, obesity is also commonly linked to altered puberty onset and
      reproductive impairment. Such an impact of energy status on the reproductive axis
      is conveyed through a number of neuropeptide hormones and metabolic cues, whose
      nature and mechanisms of action have begun to be deciphered only in recent years.
      In this context, the emergence of kisspeptins, encoded by the KiSS-1 gene, and
      their receptor, GPR54, as indispensable signals for normal pubertal maturation
      and gonadal function, has raised the possibility that the KiSS-1/GRP54 system
      might also participate in coupling body energy status and reproduction. We revise
      herein the experimental evidence, gathered in rodent models, supporting the
      contention that the hypothalamic KiSS-1 system operates as a central conduit for
      conveying metabolic information onto the centers governing reproductive function,
      through a putative leptin-kisspeptin-GnRH pathway. Admittedly, key aspects of
      this 'metabolic' network involving the KiSS-1 system, such as its different
      peripheral regulators and central effectors, have not been fully elucidated.
      Nonetheless, the proposed hypothalamic circuitry, responsible for transmitting
      metabolic information onto the reproductive axis through KiSS-1 neurons, might
      explain, at least in part, the mechanisms for the well-known alterations of
      fertility linked to conditions of disturbed energy balance in humans, from
      anorexia nervosa to morbid obesity.

PMID- 18634842
TI  - Review of predictive models for Fusarium head blight and related mycotoxin
      contamination in wheat.
AB  - Mould growth and mycotoxin production are related to plant stress caused by
      environmental factors such as: extreme weather; insect damage; inadequate storage
      conditions and incorrect fertilization; these predispose plants to mycotoxin
      contamination in the field. Fusarium species infect wheat during the flowering
      period. In addition to losses of yield, these fungi can also synthesize toxic
      components (mycotoxins) in suitable environmental conditions, thus threatening
      animal and human health. Given the severe consequences and the fact that
      mycotoxins affect production throughout the world, the ability to predict
      Fusarium head blight (FHB) and deoxynivalenol (DON) and other mycotoxin
      contamination is important to reduce the year-to-year risk for producers. Owing
      to these dangerous consequences in Argentina, Belgium, Canada, Italy, the United
      States and in Europe, computer models, based on weather variables (temperature,
      rainfall and moisture level), have been developed to predict the occurrence of
      FHB and DON contamination in wheat.

PMID- 18634843
TI  - Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small
      intestine.
AB  - Oral administration of bovine lactoferrin (bLF) inhibits carcinogenesis in the
      colon and other organs in rats, and lung metastasis in mice. A likely mechanism
      by which bLF mediates its anticarcinogenesis effects is by enhanced expression of
      cytokines and subsequent activation of immune cells. Oral administration of bLF
      enhances expression of interleukin-18 (IL-18) mRNA in the mucosa of the small
      intestine of mice. Importantly, the pepsin hydrolysate of bLF (bLFH) also induced
      expression of IL-18 mRNA in the mouse small intestine and a peptide produced by
      pepsin digestion of bLF, bovine lactoferricin (bLFcin), induced expression of
      mature IL-18 in organ culture. In addition to IL-18, bLF and bLFcin both induced
      significant increases in caspase-1 activity in peritoneal macrophages and in
      organ cultures. The increase of mature IL-18 by macrophages was inhibited by
      caspase-1 inhibitor: caspase-1 is known to cleave the proform of IL-18 to produce
      active mature IL-18. Finally, bLF also induced expression of IFNgamma by
      peritoneal macrophages. Importantly, in IFNgamma knockout (GKO) mice, bLF
      administration resulted in increased expression of caspase-1 protein, but
      induction of IL-18 mRNA, caspase-1 activity, and mature IL-18 was not observed.
      These results indicate that orally administered bLF can induce expression of
      IFNgamma and caspase-1 in the small intestine. IFNgamma in turn increases
      expression of target genes, including IL-18. Active caspase-1 then cleaves pro-IL
      18 to generate mature IL-18. Thus, bLF activates an effector pathway mediated by
      IFNgamma, caspase-1, and IL-18. We also show that ingested bLF is able to
      activate more than a single effector pathway. For example, in GKO mice while bLF
      administration could not activate the IFNgamma/caspase-1/IL-18 effector pathway,
      it was able to inhibit tumor growth and metastasis by activation of an
      IFNalpha/IL-7 effector pathway.

PMID- 18634844
TI  - Reactive oxygen species generation is modulated by mitochondrial kinases:
      correlation with mitochondrial antioxidant peroxidases in rat tissues.
AB  - Mitochondrial hexokinase (mt-HK) and creatine kinase (mt-CK) activities have been
      recently proposed to reduce the rate of mitochondrial ROS generation through an
      ADP re-cycling mechanism. Here, we determined the role of mt-HK and mt-CK
      activities in regulate mitochondrial ROS generation in rat brain, kidney, heart
      and liver, relating them to the levels of classical antioxidant enzymes. The
      activities of both kinases were significantly higher in the brain than in other
      tissues, whereas the activities of catalase (CAT), glutathione peroxidase (GPx)
      and glutathione reductase (GR) were higher in both liver and kidney mitochondria.
      In contrast, manganese superoxide dismutase (Mn-SOD) activity was not
      significantly different among these tissues. Activation of mitochondrial kinases
      by addition of their substrates increased the ADP re-cycling and thus the
      respiration by enhancing the oxidative phosphorylation. Succinate induced
      hydrogen peroxide (H(2)O(2)) generation was higher in brain than in kidney and
      heart mitochondria, and the lowest in liver mitochondria. Mitochondrial membrane
      potential (DeltaPsi(m)) and H(2)O(2) production, decreased with additions of 2
      DOG or Cr to respiring brain and kidney mitochondria but not to liver. The
      inhibition of H(2)O(2) production by 2-DOG and Cr correspond to almost 100% in
      rat brain and about 70% in kidney mitochondria. Together our data suggest that
      mitochondrial kinases activities are potent preventive antioxidant mechanism in
      mitochondria with low peroxidase activities, complementing the classical
      antioxidant enzymes against oxidative stress.

PMID- 18634845
TI  - The evolution of the ligand/receptor couple: a long road from comparative
      endocrinology to comparative genomics.
AB  - Comparative endocrinology considers the evolution of bioregulatory systems and
      the anatomical structures and molecules that constitute the neuroendocrine and
      endocrine systems. One aim of comparative endocrinology is to trace the origins
      of the main endocrine systems. The understanding of the evolution of the
      ligand/receptor couple is central to this objective. One classical approach to
      tackle this question is the characterization of receptors and ligands in various
      types of non-model organisms using as a starting point the knowledge accumulated
      on classical models such as mammals (mainly human and mouse) and arthropods (with
      Drosophila among other insects). In this review we discuss the potential caveats
      associated to this two-by-two comparison between a classical model and non-model
      organisms. We suggest that the use of an evolutionary approach involving
      comparisons of several organisms in a coherent framework permits reconstruction
      of the most probable scenarios. The use of the vast amount of genomic data now
      available, coupled to functional experiments, offers unprecedented possibilities
      to trace back the origins of the main ligand/receptor couples.

PMID- 18634846
TI  - Protective effect of erythropoietin on beta-amyloid-induced PC12 cell death
      through antioxidant mechanisms.
AB  - Erythropoietin (EPO), a haematopoietic growth factor has been reported to display
      neuroprotective properties in different animal models. In the present study, we
      investigated the neuroprotective effects of EPO on Abeta(25-35)-induced neuronal
      toxicity and its potential mechanisms in PC12 cells. Abeta(25-35) significantly
      reduced cell viability and increased the number of apoptotic-like cells. In
      addition, increased ROS production and decreased mitochondrial membrane potential
      were also found after Abeta(25-35) exposure. All of these phenotypes induced by
      Abeta(25-35) were markedly reversed by EPO. Pretreatment with EPO prior to
      Abeta(25-35) exposure significantly elevated cell viability, reduced Abeta(25-35)
      induced apoptosis, decreased ROS production, and stabilized mitochondrial
      membrane potential. Furthermore, EPO also attenuated the downstream cascade
      following ROS, including Bcl-2/Bax, and caspase-3 activation. Our results suggest
      that EPO holds potential for neuroprotection and therefore, may be promising for
      the treatment of Alzheimer's disease.

PMID- 18634847
TI  - TRAIL-mediated apoptosis in malignant glioma cells is augmented by celecoxib
      through proteasomal degradation of survivin.
AB  - Celecoxib is a cyclooxygenase 2-selective nonsteroidal anti-inflammatory drug
      (NSAID) that exhibited therapeutic activity in cancer. In this study three
      malignant glioma, U87-MG, U251 and A172, were treated with celecoxib, tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of
      both. Single treatment with celecoxib (25-100muM) for 24h resulted in a
      concentration-dependant decrease of cellular viability in U87-MG, U251 and A172.
      Combining subtoxic concentrations of celecoxib with TRAIL strongly increased cell
      death in human malignant glioma cells. After 8h treatment with celecoxib we found
      down-regulation of the inhibitor of apoptosis protein survivin that was mediated
      by proteasomal degradation. In addition, over-expression of survivin not only
      attenuated celecoxib-induced cytotoxicity but also cytotoxicity induced by the
      combination of celecoxib and TRAIL. Taken together, in malignant glioma survivin
      is a key regulator in celecoxib- and TRAIL-celecoxib-mediated cell death.

PMID- 18634848
TI  - Tracing the ventral stream for auditory speech processing in the temporal lobe by
      using a combined time series and independent component analysis.
AB  - Recent models of speech processing claim a ventral and dorsal stream for
      processing language as for the visual domain. Patients with aphasia are
      demonstrating selective disturbances within parts of these streams. Here, we are
      presenting an fMRI study, which mainly focuses on the ventral stream, i.e. the
      phonological, lexical, and semantic processing of auditory speech. We used three
      linguistic conditions: (1) listening to reversed words, (2) listening to real
      words and, (3) covert naming after short description. We analysed the temporal
      dynamics of the BOLD signal as well as the temporal dynamics of lateralisation.
      In addition, an independent component analysis (ICA) was applied. By combining
      the results from these methods, we were able to separate the areas for pure
      auditory-phonetic perception, located bilaterally in the middle and posterior
      aspects of the superior temporal lobe, from predominantly left-lateralised areas
      for semantic and lexical processing, located in posterior-inferior as well as
      anterior regions of the temporal lobe, at the temporal-parietal-junction, and in
      the inferior frontal gyrus. These two networks differed with respect to their
      time course and temporal dynamics of lateralisation, and they were separated into
      two components of the ICA analysis. By being able to separate these two networks,
      we further conclude that this complementary analysis method might also be
      relevant for exploring recovery processes in patients with aphasia.

PMID- 18634849
TI  - Tremor-correlated neuronal activity in the subthalamic nucleus of Parkinsonian
      patients.
AB  - Tremor in Parkinson's disease (PD) is generated by an oscillatory neuronal
      network consisting of cortex, basal ganglia and thalamus. The subthalamic nucleus
      (STN) which is part of the basal ganglia is of particular interest, since deep
      brain stimulation of the STN is an effective treatment for PD including
      Parkinsonian tremor. It is controversial if and how the STN contributes to tremor
      generation. In this study, we analyze neuronal STN activity in seven patients
      with Parkinsonian rest tremor who underwent stereotactic surgery for deep brain
      stimulation. Surface EMG was recorded from the wrist flexors and extensors.
      Simultaneously, neuronal spike activity was registered in different depths of the
      STN using an array of five microelectrodes. After spike-sorting, spectral
      coherence was analyzed between spike activity of STN neurons and tremor activity.
      Significant coherence at the tremor frequency was detected between EMG and
      neuronal STN activity in 76 out of 145 neurons (52.4%). In contrast, coherence in
      the beta band occurred only in 10 out of 145 neurons (6.9%). Tremor-coherent STN
      activity was widely distributed over the STN being more frequent in its dorsal
      parts (70.8-88.9%) than in its ventral parts (25.0-48.0%). Our results suggest
      that synchronous neuronal STN activity at the tremor frequency contributes to the
      pathogenesis of Parkinsonian tremor. The wide-spread spatial distribution of
      tremor-coherent spike activity argues for the recruitment of an extended network
      of subthalamic neurons for tremor generation.

PMID- 18634850
TI  - Effect of SB-750364, a specific TRPV1 receptor antagonist, on injury-induced
      ectopic discharge in the lingual nerve.
AB  - Abnormal neural activity generated at a site of nerve injury is thought to
      contribute to the development of dysaesthesia. Vanilloid receptor 1 (TRPV1), a
      transducer of noxious stimuli, may be involved in the initiation of this abnormal
      activity and could provide a useful therapeutic target. We investigated the
      effect of a specific TRPV1 antagonist (SB-750364) on injury-induced discharge in
      the lingual nerve. In 12 anaesthetised adult ferrets the left lingual nerve was
      sectioned and animals were allowed to recover for 3-7 days. In terminal
      experiments under general anaesthesia, the nerve was re-exposed and
      electrophysiological recordings made from spontaneously active axons in fine
      filaments dissected from the nerve central to both the injury site and the
      junction with the chorda tympani. SB-750364 was infused via the cephalic vein in
      order to achieve three increasing but stable systemic blood levels of the
      compound (0.3, 1.0 and 3.0 microM). Twenty-eight spontaneously active units were
      studied, with discharge frequencies ranging from 0.02 to 4.9 Hz. There was a
      significant reduction in spontaneous activity in 17 units (61%) at 1.0 microM or
      less of SB-750364 (p<0.01; Friedman test with Dunn's multiple comparisons). A
      further 4 units (14%) showed a significant reduction in activity at 3.0 microM
      (p<0.01). In the remaining 7 units (25%) the discharge was unaffected (p>0.05).
      These data show that the TRPV1 antagonist SB-750364 can reduce the level of
      spontaneous activity initiated in some axons following lingual nerve injury.

PMID- 18634851
TI  - Deletion of both ICAM-1 and C3 enhances severity of experimental autoimmune
      encephalomyelitis compared to C3-deficient mice.
AB  - Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous
      system (CNS) inflammation and leukocyte infiltration, demyelination of neurons,
      and blood-brain barrier breakdown. The development of experimental autoimmune
      encephalomyelitis (EAE), the animal model for MS is dependent on a number of
      components of the immune system including complement and adhesion molecules.
      Previous studies in our lab have examined the role of C3, the central complement
      component, and intercellular adhesion molecule-1 (ICAM-1) a key cell adhesion
      molecule involved in leukocyte trafficking to sites of inflammation including the
      CNS. In these studies we demonstrated that myelin oligodendrocyte glycoprotein
      (MOG)-induced EAE is markedly attenuated in both ICAM-1(-/-) and C3(-/-) mice.
      Given the pivotal role that these proteins play in EAE, we hypothesized that EAE
      in ICAM-1(-/-) and C3(-/-) double mutant mice would likely fail to develop.
      Unexpectedly, EAE in ICAM-1(-/-)xC3(-/-) mice was only modestly attenuated
      compared to wild type mice and significantly worse than C3(-/-) mice. Leukocyte
      infiltration was commensurate with disease severity between the three groups of
      mice. Spinal cord T cells from ICAM-1(-/-)xC3(-/-) mice produced the highest
      levels of IFN-gamma and TNF-alpha, despite reduced disease severity compared to
      wild type mice. The mechanisms behind the elevated EAE severity in ICAM-1(-/
      )xC3(-/-) mice may relate to altered homing of leukocytes or processing of self
      antigens in the double mutant background.

PMID- 18634852
TI  - Expression of the LRRK2 gene in the midbrain dopaminergic neurons of the
      substantia nigra.
AB  - A hallmark of Parkinson's disease (PD) is the progressive loss of the A9 midbrain
      dopaminergic (mDA) neurons in the substantia nigra pars compacta. Recently,
      multiple causative mutations have been identified in the leucine-rich repeat
      kinase 2 (LRRK2) gene for both familial and sporadic PD cases. Therefore, to
      investigate functional roles of LRRK2 in normal and/or diseased brain, it is
      critical to define LRRK2 expression in mDA neurons. To address whether LRRK2 mRNA
      and protein are expressed in mDA neurons, we purified DA neurons from the
      tyrosine hydroxylase (TH)-GFP transgenic mouse using FACS-sorting and analyzed
      the expression of LRRK2 and other mDA markers. We observed that all mDA markers
      tested in this study (TH, Pitx3, DAT, Nurr1 and Lmx1a) are robustly expressed
      only in GFP(+) cells, but not in GFP(-) cells. Notably, LRRK2 was expressed in
      both GFP(+) and GFP(-) cells. Consistent with this, our immunohistochemical
      analyses showed that LRRK2 is expressed in TH-positive mDA neurons as well as in
      surrounding TH-negative cells in the rat brain. Importantly, in the midbrain
      region, LRRK2 protein was preferentially expressed in A9 DA neurons of the
      substantia nigra, compared to A10 DA neurons of the ventral tegmental area.
      However, LRRK2 was also highly expressed in the cortical and hippocampal regions.
      Taken together, our results suggest that LRRK2 may have direct functional role(s)
      in the neurophysiology of A9 DA neurons and that dysfunction of these neurons by
      mutant LRRK2 may directly cause their selective degeneration.

PMID- 18634853
TI  - Regions with different evoked frequency band responses during early-stage visual
      processing distinguish mild Alzheimer dementia from mild cognitive impairment and
      normal aging.
AB  - Although diagnostic procedures have been developed for detection of mild
      cognitive impairment (MCI) and mild Alzheimer dementia (AD), more valid
      noninvasive tools are needed. In this work, we apply a procedure based on the
      evidences that different evoked frequency band responses may emerge from
      different sources during early-stage visual processing in a mental state-specific
      manner, while subjects were passively viewing a visual stimulus. In this case,
      spatial differences should arise across mental conditions such as mild Alzheimer
      dementia, mild cognitive impairment, and normal aging. With the use of EEG source
      image we found three different neural patterns in aged individuals: (1) left
      hippocampus and midbrain in mild AD, (2) left lateral orbitofrontal gyrus, left
      nucleus accumbens, caudate nucleus, thalamus, posterior cinguli, right
      precuneous, right superior parietal lobe in MCI, and (3) right lateral-medial
      orbitofrontal gyrus, caudate nucleus, thalamus, right lateral occipitotemporal
      gyrus in elderly controls. Although preliminary, these results show remarkably
      robust differences that distinguish between an age-matched control group, a group
      with MCI, and a group with mild AD. Because the method applied in this work
      differentiates among clinical entities with varying severity of cognitive
      decline, it may eventually serve as an electrophysiological marker in the early
      detection of neurodegeneration.

PMID- 18634854
TI  - Event-related synchronization of alpha activity in early Alzheimer's disease and
      mild cognitive impairment: an MEG study combining beamformer and group
      comparison.
AB  - In patients with Alzheimer's disease (AD), it is sometimes challenging to
      identify typical findings in electroencephalography (EEG) or
      magnetoencephalography (MEG) such as a slowing of the posterior dominant activity
      or an increase in slow activity. In this MEG study, we evaluated the event
      related synchronization (ERS) of alpha activity after eye closing in patients
      with early AD and mild cognitive impairment (MCI) who presented no slow MEG
      pattern. Thirteen patients with probable AD and thirteen patients with MCI, who
      met NINCDS-ADRDA and Petersen's diagnostic criteria, respectively, were enrolled.
      We also selected fourteen age-matched normal control subjects. MEG activity was
      acquired during eye-open and eye-closed states. The ERS after eye closing within
      8-15Hz frequency band was calculated and its cortical source was superimposed on
      the individual's MRI by using the beamformer implemented in Brain Electrical
      Source Analysis (BESA). The Source image was converted into a standardized image,
      and group comparisons across patients with AD, MCI and controls were performed
      using BrainVoyager QX. The averaged ERS was observed dominantly in posterior
      regions in all three groups. Significant difference in ERS was observed only for
      the comparison between AD patients and controls, with AD patients showing
      increased ERS in frontal regions. Frontal shift of posterior alpha activity was
      observed clearly in AD patients using the combination of beamformer and group
      comparison.

PMID- 18634855
TI  - Hippocalcin signaling via site-specific translocation in hippocampal neurons.
AB  - Hippocalcin is a Ca(2+)-binding protein, which belongs to the family of neuronal
      Ca(2+) sensors. It is highly expressed in the hippocampus but molecular
      mechanisms underlying its action in this part of the brain have not been
      investigated in detail. To study whether intrinsic neuronal activity could result
      in hippocalcin-mediated signal transduction we examined spontaneous and action
      potential (AP)-dependent changes in fluorescence of yellow fluorescent protein
      tagged hippocalcin (HPCA-YFP) in transiently transfected hippocampal cultured
      neurons. In 6-12 DIV neurons HPCA-YFP spontaneously translocated longitudinally
      to specific sites within diffusionally confined domains of neuronal processes.
      The translocations to these sites were expressed as fast, reversible increases in
      HPCA-YFP fluorescence coincided with a decrease in adjacent sites indicating
      genuine protein translocation. Physiologically relevant neuronal stimulation with
      short trains of action potentials also resulted in fast, simultaneous,
      reversible, and [Ca(2+)](i)-dependent translocations of HPCA-YFP to several sites
      synchronizing hippocalcin signaling in different parts of neuronal processes. The
      amount of translocated protein increased with the number of action potentials in
      a train decoding the number of APs into the amount of translocated protein. We
      conclude that hippocalcin may signal within diffusionally restricted domains of
      neuronal processes in which it might play a physiological role in Ca(2+)
      dependent local activation of specific molecular targets.

PMID- 18634856
TI  - Early life programming of hemispheric lateralization and synchronization in the
      adult medial prefrontal cortex.
AB  - Neonatal maternal separation (MS) in the rat increases the vulnerability to
      stressors later in life. In contrast, brief handling (H) in early life confers
      resilience to stressors in adulthood. Early life programming of stress reactivity
      may involve the medial prefrontal cortex (mPFC), a region which modulates various
      stress responses. Moreover, hemispheric specialization in mPFC may mediate
      adaptive coping responses to stress. In the present study, neuronal activity was
      examined simultaneously in left and right mPFC in adult rats previously subjected
      to MS, H or animal facility rearing (AFR). In vivo electrophysiology, under
      isoflurane anesthesia, was used to conduct acute recordings of unit and local
      field potential (LFP) activity in response to systemic administration of N-methyl
      beta-carboline-3-carboxamide (FG-7142), a benzodiazepine receptor partial inverse
      agonist which mimics various stress responses. MS decreased basal unit activity
      selectively in right mPFC. Basal LFP activity was reduced with MS in left and
      right mPFC, compared to AFR and H, respectively. Hemispheric synchronization of
      basal LFP activity was also attenuated by MS at lower frequencies. FG-7142
      elicited lateralized effects on mPFC activity with different early rearing
      conditions. Activity in left mPFC was greater with AFR and MS (AFR>MS), whereas
      activity was predominantly greater with H in right mPFC. Finally, compared to
      AFR, MS reduced and H enhanced hemispheric synchronization of LFP activity with
      FG-7142 treatment in a dose-dependent manner. These results indicate that
      functionally-relevant alterations in mPFC GABA transmission are programmed by the
      early rearing environment in a hemisphere-dependent manner. These findings may
      model the hemispheric specialization of mPFC function thought to mediate adaptive
      coping responses to stressors. They also suggest the possibility that early
      environmental programming of hemispheric functional coupling in mPFC is involved
      in conferring vulnerability or resilience to stressors later in life.

PMID- 18634858
TI  - A new grayanane diterpenoid from Rhododendron decorum.
AB  - A new grayanane diterpenoid, 2,3-epoxy-5beta,6beta,10alpha,13beta,16alpha
      pentahydroxy-grayanane, named craiobiotoxin IX (1), together with the known
      grayanotoxins I and IV, was isolated from the aerial part of Rhododendron
      decorum. The structure was elucidated on the basis of spectroscopic and X-ray
      diffraction analysis.

PMID- 18634857
TI  - The role of the opioid receptor-like (ORL1) receptor in motor stimulatory and
      rewarding actions of buprenorphine and morphine.
AB  - We have previously shown that the ability of buprenorphine to activate the opioid
      receptor-like (ORL1) receptor compromises its antinociceptive effect.
      Furthermore, morphine has been shown to alter the level of orphanin FQ/nociceptin
      (OFQ/N), the endogenous ligand of the ORL1 receptor, raising the possibility that
      the endogenous OFQ/N/ORL1 receptor system may be involved in the actions of these
      opioids. Thus, using mice lacking the ORL1 receptor and their wild-type
      littermates, the present study assessed the role of the ORL1 receptor in
      psychomotor stimulant and rewarding actions of buprenorphine and morphine.
      Morphine (5, 10 mg/kg) dose-dependently increased motor activity and induced
      conditioned place preference. However, the magnitude of each response was
      comparable for the mutant mice and their wild-type littermates. In contrast,
      buprenorphine (1 mg/kg) induced greater motor stimulation in ORL1 receptor
      knockout mice as compared with their wild-type littermates. Further, single
      conditioning with buprenorphine (3 mg/kg) induced place preference in mutant mice
      but not in their wild-type littermates. The results of binding assay showed that
      buprenorphine concentration-dependently (0-1000 nM) displaced specific binding of
      [(3)H]-OFQ/N in brain membrane of wild-type mice. Together, the present results
      suggest that the ability of buprenorphine to interact with the ORL1 receptor
      modulates its acute motor stimulatory and rewarding effects.

PMID- 18634859
TI  - Topi, an IS630/Tc1/mariner-type transposable element in the African malaria
      mosquito, Anopheles gambiae.
AB  - IS630/Tc1/mariner elements are diverse and widespread within insects. The African
      malaria mosquito, Anopheles gambiae, contains over 30 families of
      IS630/Tc1/mariner elements although few have been studied in any detail. To
      examine the history of Topi elements in An. gambiae populations, Topi elements
      (n=73) were sampled from five distinct populations of An. gambiae from eastern
      and western Africa and evaluated with respect to copy number, nucleotide
      diversity and insertion site-occupancy frequency. Topi 1 and 2 elements were
      abundant (10-34 per diploid genome) and highly diverse (pi=0.051). Elements from
      mosquitoes collected in Nigeria were Topi 2 elements and those from mosquitoes
      collected in Mozambique were Topi 1 elements. Of the 49 Topi transposase open
      reading frames sequenced none were found to be identical. Intact elements with
      complete transposase open reading frames were common, although based on insertion
      site-occupancy frequency data it appeared that genetic drift was the major force
      acting on these IS630/Tc1/mariner-type elements. Topi 3 elements were not
      recovered from any of the populations sampled in this study and appear to be rare
      elements in An. gambiae, possibly due to a recent introduction.

PMID- 18634860
TI  - Estrogenic activity of environmental polycyclic aromatic hydrocarbons in uterus
      of immature Wistar rats.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are an important group of environmental
      pollutants, known for their mutagenic and carcinogenic activities. Many PAHs are
      aryl hydrocarbon receptor (AhR) ligands and several recent studies have suggested
      that PAHs or their metabolites may activate estrogen receptors (ER). The present
      study investigated possible estrogenic/antiestrogenic effects of abundant
      environmental contaminants benzo[a]pyrene (BaP), benz[a]anthracene (BaA),
      fluoranthene (Fla) and benzo[k]fluoranthene (BkF) in vivo, using the immature rat
      uterotrophic assay. The present results suggest that BaA, BaP and Fla behaved as
      estrogen-like compounds in immature Wistar rats, when applied for 3 consecutive
      days at 10mg/kg/day, as documented by a significant increase of uterine weight
      and hypertrophy of luminal epithelium. These effects were likely to be mediated
      by ERalpha, a major subtype of ER present in uterus, as they were inhibited by
      treatment with ER antagonist ICI 182,780. BaA, the most potent of studied PAHs,
      induced a significant estrogenic effect within a concentration range 0.1
      50mg/kg/day; however, it did not reach the maximum level induced by reference
      estrogens. The proposed antiestrogenicity of the potent AhR agonist BkF was not
      confirmed in the present in vivo study; the exposure to BkF did not significantly
      affect the uterine weight, although a weak suppression of ERalpha immunostaining
      was observed in luminal and glandular epithelium, possibly related to its AhR
      mediated activity. The PAHs under study did not induce marked genotoxic damage in
      uterine tissues, as documented by the lack of Ser-15-phoshorylated p53 protein
      staining. With the exception of Fla, all three remaining compounds increased CYP1
      dependent monooxygenation activities in liver at the doses used, suggesting that
      the potential tissue-specific antiestrogenic effects of PAHs mediated by
      metabolization of 17beta-estradiol also cannot be excluded. Taken together, these
      environmentally relevant PAHs induced estrogenic effects in vivo, which might
      affect their toxic impact and carcinogenicity.

PMID- 18634861
TI  - Toxic effects of microbial phenolic acids on the functions of mitochondria.
AB  - Low-molecular-weight phenolic acids (PhAs) phenylacetate, phenyllactate,
      phenylpropionate, p-hydroxyphenyllactate, and p-hydroxyphenylacetate are
      essentially the products of the degradation of aromatic amino acids and
      polyphenols by the intestinal microflora. In sepsis, the concentrations of some
      of these acids in the blood increase tens of times. Assuming that these compounds
      can cause the mitochondrial dysfunction in sepsis, we examined their effects on
      respiration, the induction of pore opening, and the production of reactive oxygen
      species (ROS) in mitochondria. It was found that phenylpropionate and
      phenylacetate produce a more toxic effect on mitochondria than the other phenolic
      acids. At concentrations 0.01-0.1 mM they decreased the rate of oxidation of NAD
      dependent substrates and activated the Ca2+- and menadione-induced opening of the
      cyclosporin A-sensitive pore and the production of ROS. The disturbances caused
      by these PhAs are similar to those observed in mitochondria in sepsis, and hence
      the rise in their level may be one of the causes of mitochondrial dysfunctions.
      Phenyllactate, p-hydroxyphenyllactate, and p-hydroxyphenylacetate inhibited the
      production of ROS and pore opening, acting as antioxidants. Thus, the ability of
      PhAs to affect the mitochondrial functions, as well as an increase in their
      concentrations in sepsis (the total concentration of these PhAs in the blood is
      close to 0.1 mM), suggests that PhAs can be directly involved in the development
      of mitochondrial failure.

PMID- 18634862
TI  - Stability of the nitrogen mustard mechlorethamine in novel formulations for
      dermatological use.
AB  - Long term stability measurements were made for the nitrogen mustard
      mechlorethamine HCl at a concentration of 0.02% in six topical formulations:
      Aquaphor ointment, Transcutol, Labrasol, 10% Transcutol in Aquaphor, 10%
      Transcutol in Labrasol, and Aquaphilic ointment. The drug decomposed gradually in
      Aquaphor ointment at room temperature, dropping to 95% in 4 weeks, 85% in 12
      weeks, and 78% in 39 weeks. On the other hand, the drug decomposed rapidly in
      Aquaphilic ointment, giving an assay of less than 20% of its initial
      concentration after 24h at room temperature. Generally, mechlorethamine HCl was
      more stable in Aquaphor ointment than in formulations containing Transcutol or
      Labrasol. However, the addition of the free radical inhibitor, BHT, significantly
      enhanced the stability of mechlorethamine in Transcutol and Labrasol
      formulations. Four BHT-stabilized Transcutol and Labrasol formulations gave
      assays in ranges of 92-99% at the end of 4 weeks, 77-98% at the end of 12 weeks,
      and 38-93% at the end of 41 weeks.

PMID- 18634863
TI  - Improved adhesion to mucosal cells of water-soluble chitosan tetraalkylammonium
      salts.
AB  - Chitosan is a natural polymer whose bioadhesive properties make it a useful
      material for filming over and protecting damaged or sensitive mucosae. Much
      effort has been expended to develop this employ, and new applications are in the
      offing. The aim of the present study was to optimize the synthesis under
      sonochemical conditions of water-soluble chitosan tetraalkylammonium salts and to
      assess the mucoadhesive properties of the resulting water-soluble cationic
      polyelectrolytes. Aqueous solutions of several tetralkylammonium chitosan
      derivatives, viz. N-trimethyl- (1), N-diethylmethyl- (2), N-carboxymethyl- (3)
      and N-[N,N-diethylaminomethyl(diethyldimethylene ammonium)(n)]methylchitosan (4)
      were tested along with the parent biopolymer and its citric acid salt (5), both
      at neutral and acidic pH. We used a published technique for evaluating in vitro
      bioadhesion to isolated buccal cells, a mucosal model that can predict
      bioadhesive behavior in vivo. Derivatives 1 and 4 gave the best results.

PMID- 18634864
TI  - In vitro and in vivo anti-inflammatory effects of taheebo, a water extract from
      the inner bark of Tabebuia avellanedae.
AB  - AIM OF STUDY: Tabebuia spp. (Bignoniaceae) are native to tropical rain forests
      throughout Central and South America and have long been used as a folk medicine
      to treat bacterial infection, blood coagulation, cancer and inflammatory
      diseases. In this study, we aimed to demonstrate the ethnopharmacological
      activity of Tabebuia avellanedae in various in vitro and in vivo inflammatory
      conditions. MATERIALS AND METHODS: To do this, LPS-stimulated macrophages and
      arachidonic acid or croton oil-induced mouse ear edema models were employed.
      RESULTS: The water extract (taheebo) of Tabebuia avellanedae significantly
      suppressed the production of prostaglandin (PG) E(2) and nitric oxide (NO), and
      blocked the mRNA expression of their catalyzing enzymes (cyclooxygenase [COX)-II]
      and inducible NO synthase [iNOS], respectively), in lipopolysaccharide (LPS)
      stimulated RAW264.7 cells. The blockade of inflammatory mediators by taheebo
      seemed to be the result of the interruption of extracellular signal-related
      kinase (ERK) activation, according to immunoblotting analysis and the NO assay,
      where LPS strongly induced the phosphorylation (a hallmark of activation) of ERK,
      and U0126, a selective ERK inhibitor, was found to strongly inhibit PGE(2)
      production. Similarly, oral administration of taheebo (100mg/kg) for 1 week
      completely diminished mouse ear edema induced by arachidonic acid, an activator
      of COX-II, but not croton oil, an activator of lipoxygenase. CONCLUSIONS: These
      data suggest that the ethnopharmacological action of taheebo may be due to its
      negative modulation of macrophage-mediated inflammatory responses by suppressing
      PGE(2) production. Thus, this water extract may be developed as a new therapeutic
      remedy for various inflammatory diseases such as arthritis and atherosclerosis.

PMID- 18634865
TI  - Motility and flagellin gene expression in the fish pathogen Vibrio salmonicida:
      effects of salinity and temperature.
AB  - The success of several Vibrio species, including Vibrio cholerae, Vibrio
      anguillarum and Vibrio fischeri in colonizing their symbiont, or causing
      infection is linked to flagella-based motility. It is during early colonization
      or the initial phase of infection that motility appears to be critical. In this
      study we used Vibrio salmonicida, a psychrophilic and moderate halophilic
      bacterium that causes cold-water vibriosis in seawater-farmed Atlantic salmon
      (Salmo salar), to study motility and expression of flagellins under salt
      conditions mimicking the initial and later phases of an infection. Our results,
      which are based on motility in semi-solid agar, membrane protein proteomics,
      quantitation of flagellin gene expression, challenge infection of fish, and
      microscopy, show that V. salmonicida is highly motile, expresses elevated levels
      of flagellins, and typically contains several polar flagella under salt
      conditions that are seawater-like. In contrast, V. salmonicida cells are non
      motile and express significantly lower levels of flagellins under physiological
      like salt conditions.

PMID- 18634866
TI  - Blockade of neuronal nitric oxide synthase reduces cone cell death in a model of
      retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a group of diseases in which many different
      mutations cause rod photoreceptor cells to die and then gradually cone
      photoreceptors die due to progressive oxidative damage. In this study, we have
      shown that peroxynitrite-induced nitrosative damage also occurs. In the rd1 mouse
      model of RP, there was increased staining for S-nitrosocysteine and nitrotyrosine
      protein adducts that are generated by peroxynitrite. Peroxynitrite is generated
      from nitric oxide (NO) and superoxide radicals. After degeneration of rods,
      injection of hydroethidine resulted in strong fluorescence in the retina of rd1
      mice, indicating high levels of superoxide radicals, and this was reduced, as was
      nitrotyrosine staining, by apocynin, suggesting that overaction of NADP(H)
      oxidase is at least partially responsible. Treatment of rd1 mice with a mixture
      of nitric oxide synthase (NOS) inhibitors markedly reduced S-nitrosocysteine and
      nitrotyrosine staining and significantly increased cone survival, indicating that
      NO-derived peroxynitrite contributes to cone cell death. Treatment with 7
      nitroindazole, a relatively specific inhibitor of neuronal NOS, also
      significantly reduced cone cell death, but aminoguanidine, a relatively specific
      inhibitor of inducible NOS, did not. These data suggest that NO generated by
      neuronal NOS exacerbates oxidative damage to cones in RP and that combined
      therapy to reduce NO and oxidative stress should be considered.

PMID- 18634868
TI  - Tocochromanols, plastoquinol, and other biological prenyllipids as singlet oxygen
      quenchers-determination of singlet oxygen quenching rate constants and oxidation
      products.
AB  - Singlet oxygen quenching rate constants for tocopherol and tocotrienol homologues
      have been determined in organic solvents of different polarities, as well as for
      other biological prenyllipids such as plastoquinol, ubiquinol, and alpha
      tocopherolquinol. The obtained results showed that the quenching activity of
      tocochromanols was mainly due to the chromanol ring of the molecule and the
      activity increased with the number of the methyl groups in the ring and solvent
      polarity. Among prenylquinols, alpha-tocopherolquinol was the most active
      scavenger of singlet oxygen followed by ubiquinol and plastoquinol. The oxidation
      products of tocopherols were identified as 8a-hydroperoxy-tocopherones which are
      converted to the corresponding tocopherolquinones under acidic conditions. The
      primary oxidation products of prenylquinols, containing unsaturated side chains,
      were the corresponding prenylquinones that were further oxidized to hydroxyl side
      chain derivatives. In the case of plastochromanol, the gamma-tocotrienol
      homologue found in some seed oils, mainly the hydroxyl derivatives were formed,
      although 8a-hydroperoxy-gamma-tocopherones were also formed to a minor extent,
      both from plastochromanol and from its hydroxyl, side-chain derivatives. The
      obtained results were discussed in terms of the activity of different
      prenyllipids as singlet oxygen scavengers in vivo.

PMID- 18634867
TI  - Cytokines and lipopolysaccharides induce inducible nitric oxide synthase but not
      enzyme activity in adult rat cardiomyocytes.
AB  - There is evidence that nitric oxide (NO) formation in adult cardiomyocytes
      stimulated with lipopolysaccharide (LPS) is not commensurate with iNOS levels.
      Tetrahydrobiopterin (BH(4)) is a key factor in the stabilization and NO
      production by iNOS homodimer. Thus we hypothesized that BH(4) is a limiting
      factor for NO production in adult cardiomyocytes in response to LPS and cytokines
      (TNF-alpha, IL-1, IFN-gamma alone, or mixed). It was verified that LPS and
      cytokines induced iNOS expression which did not translate into increased nitrite
      or [(14)C]citrulline production. This response coincided with defective BH(4)
      synthesis and low GTP cyclohydrolase activity. Furthermore, supplementation with
      BH(4) and ascorbate failed to increase iNOS activity. This effect was related to
      preferential accumulation of BH(2) rather than BH(4) in these cells. Uncoupled
      iNOS activity in stimulated cells was examined using mitochondrial aconitase
      activity as an endogenous marker of superoxide anion radical (O(2)(-)) formation,
      and found not to be significantly inhibited. 2-Hydroxyethidium also was not
      significantly increased. We conclude that adult cardiomyocytes are an unlikely
      source of NO and O(2)(-) in inflammatory conditions. This finding adds a new and
      unexpected layer of complexity to our understanding of the responses of the adult
      heart to inflammation.

PMID- 18634869
TI  - Exhaled 8-isoprostane and prostaglandin E(2) in patients with stable and unstable
      cystic fibrosis.
AB  - We measured 8-isoprostane, a biomarker of oxidative stress, and prostaglandin
      (PG) E(2) in exhaled breath condensate in 36 stable and 14 unstable cystic
      fibrosis (CF) patients, and in 15 healthy age-matched controls. We studied the
      relationships of these eicosanoids with clinical, radiological, and systemic
      inflammatory parameters. Compared with controls [15.5 (11.5-17.0) pg/ml] exhaled
      8-isoprostane was increased in stable CF patients [30.5 (25.3-36.0) pg/ml,
      P<0.001]. Unstable CF patients had higher exhaled 8-isoprostane levels [47.5
      (44.0-50.0) pg/ml, P<0.001] than stable CF patients. Unlike PGE(2), exhaled 8
      isoprostane was negatively correlated with FEV(1) (r=-0.67; P<0.0001; r=-0.63;
      P<0.02) and Shwachman score (r=-0.43, P=0.012; r=-0.58, P=0.031) and positively
      correlated with Chrispin-Norman score (r=0.51, P<0.002; r=0.56, P=0.039) in
      stable and unstable CF patients, respectively. No correlation was observed with C
      reactive protein. Compared with controls [41.0 (29.0-50.0) pg/ml], exhaled PGE(2)
      was also elevated in stable [72.0 (64.3-81.8) pg/ml, P<0.001) and, to a greater
      extent, in unstable CF patients [83.0 (74.3-91.3) pg/ml, P<0.001). In patients
      with CF, exhaled 8-isoprostane and PGE(2) could be a useful marker of disease
      severity.

PMID- 18634870
TI  - HO-1 and JAK-2/STAT-1 signals are involved in preferential inhibition of iNOS
      over COX-2 gene expression by newly synthesized tetrahydroisoquinoline alkaloid,
      CKD712, in cells activated with lipopolysacchride.
AB  - We found that CKD712, an S enantiomer of YS49, strongly inhibited inducible
      nitric oxide synthase (iNOS) and NO induction but showed a weak inhibitory effect
      on cyclooxygenase-2 (COX-2) and PGE(2) induction in LPS-stimulated RAW 264.7
      cells. We, therefore, investigated the molecular mechanism(s) responsible for
      this by using CKD712 in LPS-activated RAW264.7 cells. Treatment with either
      SP600125, a specific JNK inhibitor or TPCK, a NF-kappaB inhibitor, but neither
      ERK inhibitor PD98059 nor p38 inhibitor SB203580, significantly inhibited LPS
      mediated iNOS and COX-2 induction. CKD712 inhibited NF-kappaB (p65) activity and
      translocation but failed to prevent JNK activation. However, AG490, a specific
      JAK-2/STAT-1 inhibitor, efficiently prevented LPS-mediated iNOS induction but not
      the induction of COX-2, and CKD712 completely blocked STAT-1 phosphorylation by
      LPS, suggesting that the NF-kappaB and JAK-2/STAT-1 pathways but not the JNK
      pathway are important for CKD712 action. Interestingly, CKD712 induced heme
      oxygenase 1 (HO-1) gene expression in LPS-treated cells. LPS-induced NF-kappaB
      and STAT-1 activation was partially prevented by HO-1 overexpression.
      Furthermore, HO-1 siRNA partly reversed not only the LPS-induced NF-kappaB
      activation and STAT-1 phosphorylation but also inhibition of these actions by CKD
      712. Additionally, silencing HO-1 by siRNA prevented CKD712 from inhibiting iNOS
      expression but not COX-2. When examined plasma NO and PGE(2) levels and iNOS and
      COX-2 protein levels in lung tissues of mice injected with LPS (10 mg/kg),
      pretreatment with CKD712 greatly prevented NO and iNOS induction in a dose
      dependent manner and slightly affected PGE(2) and COX-2 production as expected.
      Taken together, we conclude that inhibition of JAK-2/STAT-1 pathways by CKD 712
      is critical for the differential inhibition of iNOS and COX-2 by LPS in vitro and
      in vivo where HO-1 induction also contributes to this by partially modulating JAK
      2/STAT-1 pathways.

PMID- 18634871
TI  - Bile acids and signal transduction: role in glucose homeostasis.
AB  - Bile acids are mainly recognized for their role in dietary lipid absorption and
      cholesterol homeostasis. However, recent progress in bile acid research suggests
      that bile acids are important signaling molecules that play a role in glucose
      homeostasis. Among the various supporting evidence, several reports have
      demonstrated an improvement of the glycemic index of type 2 diabetic patients
      treated with diverse bile acid binding resins. Herein, we review the diverse
      interactions of bile acids with various signaling/response pathways, including
      calcium mobilization and protein kinase activation, membrane receptor-mediated
      responses, and nuclear receptor responses. Some of the effects of the bile acids
      are direct through the activation of specific receptors, i.e., TGR5, CAR, VDR,
      and FXR, while others imply modulation of the hormonal, growth factor and/or
      neuromediator responses, i.e., glucagon, EGF, and acetylcholine. We also discuss
      recent evidence implicating the interaction of bile acids with glucose
      homeostasis mechanisms, with the integration of our understanding of how the
      signaling mechanisms modulated by bile acid could regulate glucose metabolism.

PMID- 18634872
TI  - The ubiquitin-proteasome system in cardiac dysfunction.
AB  - Since proteins play crucial roles in all biological processes, the finely tuned
      equilibrium between their synthesis and degradation regulates cellular
      homeostasis. Controlling the quality of proteome informational content is
      essential for cell survival and function. After initial synthesis, membrane and
      secretory proteins are modified, folded, and assembled in the endoplasmic
      reticulum, whereas other proteins are synthesized and processed in the cytosol.
      Cells have different protein quality control systems, the molecular chaperones,
      which help protein folding and stabilization, and the ubiquitin-proteasome system
      (UPS) and lysosomes, which degrade proteins. It has generally been assumed that
      UPS and lysosomes are regulated independently and serve distinct functions. The
      UPS degrades both cytosolic, nuclear proteins, and myofibrillar proteins, whereas
      the lysosomes degrade most membrane and extracellular proteins by endocytosis as
      well as cytosolic proteins and organelles via autophagy. Over the last two
      decades, the UPS has been increasingly recognized as a major system in several
      biological processes including cell proliferation, adaptation to stress and cell
      death. More recently, activation or impairment of the UPS has been reported in
      cardiac disease and recent evidence indicate that autophagy is a key mechanism to
      maintain cardiac structure and function. This review mainly focuses on the UPS
      and its various components in healthy and diseased heart, but also summarizes
      recent data suggesting parallel activation of the UPS and autophagy in cardiac
      disease.

PMID- 18634873
TI  - RAX is required for fly neuronal development and mouse embryogenesis.
AB  - RAX was originally discovered as the unique cellular activator for the dsRNA
      dependent, interferon-inducible protein kinase PKR. Recent findings indicate that
      RAX is also a critical component of the RNA-induced silencing complex and a
      regulator of transcription. Here we report novel phenotypes for both fruit flies
      carrying a transposon insertion in the 5' UTR of dRax (independently identified
      as loqs/R3D1) and mice with a deletion of the entire Rax gene. In Drosophila we
      observe a high level of dRax expression in the developing nerve cord. Mutant fly
      embryos homozygous for the insertion dRax[f00791] display highly abnormal
      commissural axon structure of the CNS and 70% of the flies homozygous for the
      mutant allele die prior to adulthood. Surviving male flies have reduced fertility
      and female flies are sterile. Furthermore, these flies appear to have a severe
      defect in nervous system coordination or neuromuscular function resulting in
      significantly reduced locomotion. Mice were also generated that are heterozygous
      for a deletion of the entire Rax gene (exons 1-8). While mice that are
      heterozygous for the mutant allele are viable and appear normal, we are unable to
      obtain mice homozygous for this mutant allele. Furthermore, we have not observed
      any embryo obtained by mating heterozygous mice at either E3.5, 7, or 14 that is
      nullizygous for the Rax gene. Since Rax is expressed in preimplantation
      blastocysts, these data indicate that deletion of the entire Rax gene is
      embryonic lethal in mice at a preimplantation stage of development. Collectively,
      these findings in two different species illustrate the importance of RAX for
      embryonic development.

PMID- 18634874
TI  - Superior antitumor efficiency of cisplatin-loaded nanoparticles by intratumoral
      delivery with decreased tumor metabolism rate.
AB  - cis-Dichlorodiamminoplatinum (II) (cisplatin) has demonstrated extraordinary
      activities against a variety of solid tumors. However, the clinical efficacy is
      contrasted by its toxicity profile. To reduce the toxicity and enhance the
      circulation time of cisplatin, core-shell structure nanoparticles were prepared
      from block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (mPEG
      PCL). Cisplatin was incorporated into the nanoparticles with high encapsulation
      efficiency more than 75%. Controlled release of cisplatin was observed in a
      sustained manner. In vitro cytotoxicity studies proved the efficacy of cisplatin
      loaded nanoparticles against BGC823 and H(22) cells in a dose and time-dependent
      manner. Furthermore, intratumoral administration was applied to improve the tumor
      targeted delivery in the in vivo evaluation. Compared with free cisplatin,
      cisplatin-loaded nanoparticles exhibited superior antitumor effect by delaying
      tumor growth when delivered intratumorally, while no significant improvement was
      observed when they were administrated intraperitoneally. Positron emission
      tomography/computed tomography (PET/CT) imaging was utilized for the first time
      to detect the declined (18)F-labeled 2-fluoro-2-deoxy-d-glucose ((18)F-FDG)
      uptake of the tumor in mice receiving cisplatin-loaded nanoparticles
      intratumorally. These results suggest that polymeric nanoparticles with core
      shell structures are promising for further studies as drug delivery carriers, and
      intratumoral delivery of drug-loaded nanoparticles could be a probable clinically
      useful therapeutic regimen.

PMID- 18634875
TI  - Uncovering mechanisms of bistability in biological systems.
AB  - As the systems biology era progresses, theoreticians and experimentalists
      continue uncovering the molecular mechanisms that underlie the regulation of
      complex cellular phenomena, including those governing proliferation,
      differentiation, and death. The discovery of bistability in cellular responses
      and their signaling pathways has become a recurring theme, and prompted strong
      interest in understanding both the design and function of these networks.
      Modeling these systems has been crucial in assisting experimentalists to better
      understand how this and other types of behavior can emerge from a subset of
      regulators, and also to analyze and identify systems-level characteristics that
      would otherwise be difficult to intuit. In this review, recent advances in both
      theoretical and experimental work investigating the mechanistic as well as
      biological basis for bistability will be presented. These will include the role
      of positive feedback loops, the potential function of dual phosphorylation
      cycles, and substrate competition as a means of generating ultrasensitivity.

PMID- 18634876
TI  - Membranes: reading between the lines.

PMID- 18634877
TI  - Biological X-ray absorption spectroscopy (BioXAS): a valuable tool for the study
      of trace elements in the life sciences.
AB  - Using X-ray absorption spectroscopy (XAS) the binding modes (type and number of
      ligands, distances and geometry) and oxidation states of metals and other trace
      elements in crystalline as well as non-crystalline samples can be revealed. The
      method may be applied to biological systems as a 'stand-alone' technique, but it
      is particularly powerful when used alongside other X-ray and spectroscopic
      techniques and computational approaches. In this review, we highlight how
      biological XAS is being used in concert with crystallography, spectroscopy and
      computational chemistry to study metalloproteins in crystals, and report recent
      applications on relatively rare trace elements utilised by living organisms and
      metals involved in neurodegenerative diseases.

PMID- 18634878
TI  - Renin-aldosterone response, urinary Na/K ratio and growth in
      pseudohypoaldosteronism patients with mutations in epithelial sodium channel
      (ENaC) subunit genes.
AB  - Multi-system pseudohypoaldosteronism (PHA) is a rare syndrome of aldosterone
      unresponsiveness characterized by symptoms of severe salt-losing caused by
      mutations in one of the genes that encode alpha, beta or gamma subunit of
      epithelial sodium channels (ENaC). We examined long-term changes in the renin
      aldosterone response in patients with different mutations. Four PHA patients were
      followed-up for 7-22 years. Patient A with a heterozygous Gly327Cys missense
      mutation in alphaENaC is a mild case and patients B, C and D are severe cases.
      Two additional patients with renal PHA served as controls. In patient A, serum
      aldosterone and plasma renin activity (PRA) decreased with age, PRA reaching near
      normal values at age 11. In contrast, patients B-D showed a positive correlation
      between age and aldosterone (r>0.86 for all). In patient B with Arg508 stop
      mutation, aldosterone reached 166 nmol/L at age 19 (>300-fold higher than
      normal). Urinary Na/K ratios normalized gradually with age in all patients.
      Growth curves of the patients were reflective of the severity of PHA and
      compliance with salt therapy. Functional expression studies in oocytes showed
      that ENaC with alphaGly327Cys mutation, as observed in patient A, showed nearly
      40% activity of the wild type ENaC. In contrast, stop mutation as in patient B
      reduces ENaC activity to less than 5% of the normal. Our results demonstrate
      distinct genotype-phenotype relationships in multi-system PHA patients. The
      degree of ENaC function impairment affects differently the renin-aldosterone
      system and urinary Na/K ratios. The differences observed are age-dependent and
      PHA form specific.

PMID- 18634880
TI  - Tracking single molecules in the live cell plasma membrane-Do's and Don't's.
AB  - In recent years, the development of fast and highly sensitive microscopy has
      changed the way of thinking of cell biologists: it became more and more important
      to study the structural origin for cellular function, and industry turned its
      attention to the improvement of the required instruments. Optical microscopy has
      now reached a milestone in sensitivity by resolving the signal of a single,
      fluorescence-labeled biomolecule within a living cell. First steps towards these
      pioneering studies were set by methods developed in the late eighties for
      tracking single biomolecules labeled with fluorescent latex spheres or gold
      particles. Meanwhile, a time-resolution of milliseconds for imaging weakly
      fluorescent cellular structures like small organelles, vesicles, or even single
      molecules is state-of-the-art. The advances in the fields of microscopy brought
      new cell biological questions into reach. The investigation of a single
      fluorescent molecule-or simultaneously of an ensemble of individual molecules
      provides principally new information, which is generally hidden in ensemble
      averaged signals of molecules. In this paper we describe strategies how to make
      use of single molecule trajectories for deducing information about nanoscopic
      structures in a live cell context. In particular, we focus our discussion on
      elucidating the plasma membrane organization by single molecule tracking. A
      diffusing membrane constituent--e.g. a protein or a lipid--experiences a manifold
      of interactions on its path: the most rapid interactions represent the driving
      force for free diffusion; stronger or correlated interactions can be frequently
      observed as subdiffusive behavior. Correct interpretation of the data has the
      potential to shine light on this enigmatic organelle, where membrane rafts,
      protein microdomains, fences and pickets still frolic through the text-book
      sketches. We summarize available analytical models and point out potential
      pitfalls, which may result in quantitative or three even qualitative
      misinterpretations.

PMID- 18634879
TI  - Location and connectivity determine GABAergic interneuron survival in the brains
      of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited
      neurodegenerative diseases. Sheep affected with the CLN6 form provide a valuable
      model to investigate underlying disease mechanisms from preclinical stages.
      Excitatory neuron loss in these sheep is markedly regional, localized early
      reactive changes accurately predicting neuron loss and subsequent symptom
      development. This investigation of GABAergic interneuron loss revealed similar
      regional effects that correlate with symptoms. Loss of parvalbumin positive
      neurons from the affected cortex was apparent at four months and became profound
      by 19 months, as was somatostatin positive neuron loss to a lesser extent.
      Conversely calbindin and neuropeptide Y positive neurons were relatively
      preserved and calretinin staining temporarily increased. Staining of subcortical
      regions was more intense but subcortical architecture remained relatively intact.
      Discrete subcortical changes followed from cortical changes in interconnected
      regions. These data highlight cellular location and interconnectivity as the
      major determinants of neuron survival, rather than phenotype.

PMID- 18634881
TI  - Fluorescence correlation spectroscopy for the study of membrane dynamics and
      protein/lipid interactions.
AB  - Fluorescence correlation spectroscopy (FCS) is a powerful technique to study
      dynamic biomolecular processes. It allows the estimation of concentrations,
      diffusion coefficients, molecular interactions, and other processes causing
      fluctuations in the fluorescence intensity, thus yielding information about
      aggregation processes, enzymatic reactions, or partition coefficients. During the
      last years, FCS has been successfully applied to model and cellular membranes,
      proving to be a promising tool for the study of membrane dynamics and
      protein/lipid interactions. Here we describe the theoretical basis of FCS and
      some practical implications for its application in membrane studies. We discuss
      sources of potential artifacts, such as membrane undulations, positioning of the
      detection volume, and photobleaching. Special attention is paid to aspects
      related to instrumentation and sample preparation as well as data acquisition and
      analysis. Finally, we comment on some strategies recently developed for the
      specific improvement of FCS measurements on membranes.

PMID- 18634882
TI  - Co-expression of proteinase inhibitor enhances recombinant human granulocyte
      macrophage colony stimulating factor production in transgenic rice cell
      suspension culture.
AB  - The synthetic gene (sPI-II) harboring the chymotrypsin (C1) and trypsin (T1)
      inhibitor domains of the Nicotiana alata serine proteinase inhibitor II gene has
      been previously expressed, and extracellular protease activity was shown to be
      reduced in the suspension culture medium. In this study, the sPI-II gene was
      introduced into transgenic rice cells expressing rhGM-CSF (recombinant human
      granulocyte-macrophage colony-stimulating factor), in an effort to reduce
      protease activity and increase rhGM-CSF accumulation in the suspension culture
      medium. The integration and expression of the introduced sPI-II gene in the
      transgenic rice cells were verified via genomic DNA PCR amplification and
      Northern blot analysis, respectively. Relative protease activity was found to
      have been reduced and rhGM-CSF production was increased 2-fold in the co
      transformed cell suspension culture with rhGM-CSF and the sPI-II gene, as
      compared with that observed in the transformed cell suspension culture expressing
      rhGM-CSF only. These results indicate that a transformed plant cell suspension
      culture system expressing the proteinase inhibitor can be a useful tool for
      increasing recombinant protein production.

PMID- 18634883
TI  - Optimized expression and purification of myristoylated human neuronal calcium
      sensor 1 in E. coli.
AB  - We have developed a protocol to produce large quantities of high purity
      myristoylated and non-myristoylated neuronal calcium sensor 1 (NCS-1) protein.
      NCS-1 is a member of the neuronal calcium sensor (NCS) family and plays an
      important role in modulating G-protein signaling and exocytosis pathways in
      cells. Many of these functions are calcium-dependent and require NCS-1 to be
      modified with an N-terminal myristoyl moiety. In our system, a C-terminally 6x
      His-tagged variant of NCS-1 was co-expressed with yeast N-myristoyltransferase
      (NMT) in ZYP-5052 auto-induction media supplemented with sodium myristate (100
      200 microM). With optimized growth conditions and a high capacity metal affinity
      purification scheme, >50mg of homogenous myristoylated NCS-1 is obtained from 1L
      of culture in a single step. The properties of the C-terminally tagged NCS-1
      variants are indistinguishable from those reported for untagged NCS-1. Using this
      system, we have also isolated and characterized mutant NCS-1 proteins that have
      attenuated (NCS-1 E120Q) and abrogated (NCS-1 DeltaEF) ability to bind calcium.
      The large quantities of NCS-1 proteins isolated from small culture volumes of
      auto-inducible media will provide the necessary reagents for further biochemical
      and structural characterization. The affinity tag at the C-terminus of the
      protein provides a suitable reagent for easily identifying binding partners of
      the various NCS-1 constructs. Additionally, this method could be used to produce
      other recombinant proteins of the NCS family, and may be extended to express and
      isolate myristoylated variants of other proteins.

PMID- 18634884
TI  - Molecular and morphological adaptations in compressed articular cartilage by
      polarized light microscopy and Fourier-transform infrared imaging.
AB  - Fifteen articular cartilage-bone specimens from one canine humeral joint were
      compressed in the strain range of 0-50%. The deformation of the extracellular
      matrices in cartilage was preserved and the same tissue sections were studied
      using polarized light microscopy (PLM) and Fourier-transform infrared imaging
      (FTIRI). The PLM results show that the most significant changes in the apparent
      zone thickness due to 'reorganization' of the collagen fibrils based on the
      birefringence occur between 0% and 20% strain values, where the increase in the
      superficial zone and decrease in the radial zone thicknesses are approximately
      linear with the applied strain. The FTIRI anisotropy results show that the two
      amide components with bond direction perpendicular to the external compression
      retain anisotropy (amide II in the superficial zone and amide I in the radial
      zone). In contrast, the measured anisotropy from the two amide components with
      bond direction parallel to the external compression changes their anisotropy
      significantly (amide I in the superficial zone and amide II in the radial zone).
      Statistical analysis shows that there is an excellent correlation (r=0.98)
      between the relative depth of the minimum retardance in PLM and the relative
      depth of the amide II anisotropic cross-over. The changes in amide anisotropies
      in different histological zones are explained by the strain-dependent tipping
      angle of the amide bonds. These depth-dependent adaptations to static loading in
      cartilage's morphological structure and chemical distribution could be useful in
      the future studies of the early diseased cartilage.

PMID- 18634885
TI  - Multiscale structure of calcite fibres of the shell of the brachiopod
      Terebratulina retusa.
AB  - The shells of rhynchonelliform brachiopods have an outer (primary) layer of
      acicular calcite and an inner (secondary) layer of calcite fibres which are
      parallel to the shell exterior. Atomic force microscopy (AFM) reveals that these
      fibres are composed of large triangular nanogranules of about 600-650 nm along
      their long axis. The nanogranules are composites of organic and inorganic
      components. As the shell grows, the fibres elongate with the calcite c-axis
      perpendicular to the fibre axis as demonstrated by electron backscatter
      diffraction (EBSD). Thus, despite being a composite structure comprising granules
      that are themselves composites, each fibre is effectively a single crystal. The
      combination of AFM and EBSD reveals the details of the structure and
      crystallography of these fibres. This knowledge serves to identify those aspects
      of biological control that must be understood to enable comprehension of the
      biological control exerted on the construction of these exquisite biomineral
      structures.

PMID- 18634886
TI  - A chronic 1 year assessment of MRI contrast agent-labelled neural stem cell
      transplants in stroke.
AB  - Non-invasive identification of transplanted neural stem cells in vivo by pre
      labelling with contrast agents may play an important role in the translation of
      cell therapy to the clinic. Understanding the impact of these labels on the
      cells' ability to repair is therefore vital. In rats with middle cerebral artery
      occlusion (MCAo), a model of stroke, the transhemispheric migration of MHP36
      cells labelled with the bimodal contrast agent GRID was detected on magnetic
      resonance images (MRI) up to 4 weeks following transplantation. However, compared
      to MHP36 cells labelled with the red fluorescent dye PKH26, GRID-labelled
      transplants did not significantly improve behaviour, and performance was akin to
      non-treated animals. Likewise, the evolution of anatomical damage as assessed by
      serial, T(2)-weighted MRI over 1 year indicated that GRID-labelled transplants
      resulted in a slight increase in lesion size compared to MCAo-only animals,
      whereas the same, PKH26-labelled cells significantly decreased lesion size by
      35%. Although GRID labelling allows the in vivo identification of transplanted
      cells up to 1 month after transplantation, it is likely that some is gradually
      degraded inside cells. The translation of cellular imaging therefore does not
      only require the in vitro assessment of contrast agents on cellular functions,
      but also requires the chronic, in vivo assessment of the label on the stem cells'
      ability to repair in preclinical models of neurological disease.

PMID- 18634888
TI  - Catechol-O-methyltransferase val158met genotype influences neural processing of
      reward anticipation.
AB  - Reward processing depends critically on dopaminergic neurotransmission in the
      ventral striatum. The common polymorphism val(158)met of catechol-O
      methyltransferase (COMT) accounts for significant interindividual variations in
      dopamine (DA) degradation, although the direct effect of COMT on striatal DA
      might be limited. Using fMRI we assessed the influence of COMT val(158)met
      genotype on brain activations elicited by the anticipation of monetary gains and
      losses in forty-four healthy volunteers. We found that the met(158) allele, which
      is presumably linked to higher synaptic DA levels, was associated with higher
      responses in ventral striatum to loss incentives. There was a linear relationship
      between the number of met(158) alleles and ventral striatal activity.
      Furthermore, we observed a similar gene-dose effect in the anterior temporal
      cortex, a region that has been linked to the coupling of sensory information with
      emotional contents. Temporal cortex also showed enhanced connectivity to the
      ventral striatum during the processing of incentive stimuli. Increased ventral
      striatal reactivity to loss incentives related to the met(158) allele might
      contribute to the observed association of the met(158) allele to higher loss
      aversion behaviour. Current evidence and our results are compatible with an
      interpretation that construes this effect of COMT genotype on striatal reactivity
      as a result of a cortico-striatal interaction.

PMID- 18634887
TI  - Cortical source estimates of gamma band amplitude and phase are different in
      schizophrenia.
AB  - Reductions in gamma band phase synchrony and evoked power have been reported in
      schizophrenic subjects in response to auditory stimuli. These results have been
      observed in the EEG at one or two electrode sites. We wished to extend these
      results using magnetic field data to estimate the responses at the neural
      generators themselves in each hemisphere. Whole head magnetoencephalographic
      (MEG) recordings were used to estimate the phase and amplitude behavior of
      sources in primary auditory cortex in both hemispheres of schizophrenic and
      comparison subjects. Both ipsi- and contralateral cases were evaluated using a
      driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus.
      We used source space projection (SSP) to collapse the magnetic field data into
      estimates of the time course of source strengths in individual trials. Complex
      wavelet based time-frequency decomposition was used to compute inter-trial phase
      locking factor (PLF), and mean evoked and induced amplitude for each cortical
      generator. Schizophrenic subjects showed reduced SSP PLF and evoked source
      strength for contralateral generators responding to the driving stimulus in both
      hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the
      transient window were reduced. In contrast, subjects with schizophrenia exhibited
      higher induced 40 Hz power to both stimulus types, consistent with the reduced
      PLF findings. The method of SSP combined with wavelet based complex demodulation
      produces a significant improvement in signal-to-noise ratio, and directly
      estimates the activity of the cortical generators responsible for gamma band
      auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment
      of generation and phase locking of this activity in auditory cortex, suggesting
      an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell
      activity.

PMID- 18634889
TI  - Sparse linear regression for reconstructing muscle activity from human cortical
      fMRI.
AB  - In humans, it is generally not possible to use invasive techniques in order to
      identify brain activity corresponding to activity of individual muscles. Further,
      it is believed that the spatial resolution of non-invasive brain imaging
      modalities is not sufficient to isolate neural activity related to individual
      muscles. However, this study shows that it is possible to reconstruct muscle
      activity from functional magnetic resonance imaging (fMRI). We simultaneously
      recorded surface electromyography (EMG) from two antagonist muscles and motor
      cortices activity using fMRI, during an isometric task requiring both reciprocal
      activation and co-activation of the wrist muscles. Bayesian sparse regression was
      used to identify the parameters of a linear mapping from the fMRI activity in
      areas 4 (M1) and 6 (pre-motor, SMA) to EMG, and to reconstruct muscle activity in
      an independent test data set. The mapping obtained by the sparse regression
      algorithm showed significantly better generalization than those obtained from
      algorithms commonly used in decoding, i.e., support vector machine and least
      square regression. The two voxel sets corresponding to the activity of the
      antagonist muscles were intermingled but disjoint. They were distributed over a
      wide area of pre-motor cortex and M1 and not limited to regions generally
      associated with wrist control. These results show that brain activity measured by
      fMRI in humans can be used to predict individual muscle activity through Bayesian
      linear models, and that our algorithm provides a novel and non-invasive tool to
      investigate the brain mechanisms involved in motor control and learning in
      humans.

PMID- 18634890
TI  - Visuospatial contextual processing in the parietal cortex: an fMRI investigation
      of the induced Roelofs effect.
AB  - Neighboring contextual elements can dramatically affect the manner in which the
      brain processes the perceptual characteristics of an object. Indeed, many well
      known visual illusions rely on misleading contextual cues to create
      misperceptions of size, length or orientation (e.g., in the Ebbinghaus, Muller
      Lyer or rod-and-frame illusions, respectively). However, little is known about
      the brain regions underlying these integrative computations. The current study
      used fMRI to delineate the brain areas responsible for processing visuospatial
      contextual information. Participants were asked to determine whether a small
      target was positioned left or right of midline in the presence of an offset
      rectangle designed to induce a shift in the participant's perception of straight
      ahead (the induced Roelofs effect). We found localized, bilateral regions in
      superior parietal cortex and precuneus that were specifically active when
      participants judged the target location in the presence of this shifted context;
      significantly less activation was present when a color judgment was made with
      identical stimuli, or when the location judgment was made without a Roelofs
      inducing frame. We propose that this portion of parietal cortex is selectively
      involved in processing visuospatial contextual information. Additional findings
      support the notion that perceptual judgments of target location based on an
      egocentric frame of reference fall within the purview of the dorsal stream of
      visual processing, rather than the ventral stream.

PMID- 18634891
TI  - Age-related changes in neural activity during performance matched working memory
      manipulation.
AB  - A long-standing assumption in the cognitive aging literature is that performance
      on working memory (WM) tasks involving serial recall is relatively unaffected by
      aging, whereas tasks that require the rearrangement of items prior to recall are
      more age-sensitive. Previous neuroimaging studies of WM have found age-related
      increases in neural activity in frontoparietal brain regions during simple
      maintenance tasks, but few have examined whether there are age-related
      differences that are specific to rearranging WM items. In the current study,
      older and younger adults' brain activity was monitored using functional magnetic
      resonance imaging (fMRI) as they performed WM tasks involving either maintenance
      or manipulation (letter-number sequencing). The paradigm was developed so that
      performance was equivalent across age groups in both tasks, and the manipulation
      condition was not more difficult than the maintenance condition. In younger
      adults, manipulation-related increases in activation occurred within a very focal
      set of regions within the canonical brain WM network, including left posterior
      prefrontal cortex and bilateral inferior parietal cortex. In contrast, older
      adults showed a much wider extent of manipulation-related activation within this
      WM network, with significantly increased activity relative to younger adults
      found within bilateral PFC. The results suggest that activation and age
      differences in lateral PFC engagement during WM manipulation conditions may
      reflect strategy use and controlled processing demands rather than reflect the
      act of manipulation per se.

PMID- 18634892
TI  - Genetic structure and genealogy in the Sphagnum subsecundum complex (Sphagnaceae:
      Bryophyta).
AB  - Allopolyploidy is probably the most extensively studied mode of plant speciation
      and allopolyploid species appear to be common in the mosses (Bryophyta). The
      Sphagnum subsecundum complex includes species known to be gametophytically
      haploid or diploid, and it has been proposed that the diploids (i.e., with
      tetraploid sporophytes) are allopolyploids. Nucleotide sequence and
      microsatellite variation among haploids and diploids from Newfoundland and
      Scandinavia indicate that (1) the diploids exhibit fixed or nearly fixed
      heterozygosity at the majority of loci sampled, and are clearly allopolyploids,
      (2) diploids originated independently in North America and Europe, (3) the
      European diploids appear to have the haploid species, S. subsecundum, as the
      maternal parent based on shared chloroplast DNA haplotypes, (4) the North
      American diploids do not have the chloroplast DNA of any sampled haploid, (5)
      both North American and European diploids share nucleotide and microsatellite
      similarities with S. subsecundum, (6) the diploids harbor more nucleotide and
      microsatellite diversity than the haploids, and (7) diploids exhibit higher
      levels of linkage disequilibrium among microsatellite loci. An experiment
      demonstrates significant artifactual recombination between interspecific DNAs
      coamplified by PCR, which may be a complicating factor in the interpretation of
      sequence-based analyses of allopolyploids.

PMID- 18634893
TI  - Development of an in vitro drug-drug interaction assay to simultaneously monitor
      five cytochrome P450 isoforms and performance assessment using drug library
      compounds.
AB  - INTRODUCTION: Inhibition of cytochrome P450 (CYP) is a principal mechanism for
      metabolism-based drug-drug interactions (DDIs). This article describes a robust,
      high-throughput CYP-mediated DDI assay using a cocktail of 5 clinically relevant
      probe substrates with quantification by liquid chromatography/tandem mass
      spectrometry (LC/MS-MS). METHODS: The assay consisted of human liver microsomes
      and a cocktail of probe substrates metabolized by the five major CYP isoforms
      (tacrine for CYP1A2, diclofenac for CYP2C9, (S)-mephenytoin for CYP2C19,
      dextromethorphan for CYP2D6 and midazolam for CYP3A4). The assay was fully
      automated in both 96- and 384-well formats. RESULTS: A series of experiments were
      conducted to define the optimal kinetic parameters and solvent concentrations, as
      well as, to assess potential reactant and product interference. The assay was
      validated against known CYP inhibitors (miconazole, sulfaphenazole, ticlopidine,
      quinidine, ketoconazole, itraconazole, fluoxetine) and evaluated in a screening
      environment by testing 9494 compounds. DISCUSSION: Our findings show that this
      assay has application in early stage drug discovery to economically, reliably and
      accurately assess compounds for DDIs.

PMID- 18634894
TI  - Gabaergic mechanisms of hypothalamic nuclei in the expression of conditioned
      fear.
AB  - The amygdala, the dorsal periaqueductal gray (dPAG), and the medial hypothalamus
      have long been recognized to be a neural system responsible for the generation
      and elaboration of unconditioned fear in the brain. It is also well known that
      this neural substrate is under a tonic inhibitory control exerted by GABA
      mechanisms. However, whereas there is a growing body of evidence to suggest that
      the amygdala and dPAG are also able to integrate conditioned fear, it is still
      unclear, however, how the distinct hypothalamic nuclei participate in fear
      conditioning. In this work we aimed to examine the extent to which the gabaergic
      mechanisms of this brain region are involved in conditioned fear using the fear
      potentiated startle (FPS). Muscimol, a GABA-A receptor agonist, and
      semicarbazide, an inhibitor of the GABA synthesizing enzyme glutamic acid
      decarboxylase (GAD), were used as an enhancer and inhibitor of the GABA
      mechanisms, respectively. Muscimol and semicarbazide were injected into the
      anterior hypothalamus (AHN), the dorsomedial part of the ventromedial nucleus
      (VMHDM), the dorsomedial (DMH) or the dorsal premammillary (PMD) nuclei of male
      Wistar rats before test sessions of the fear conditioning paradigm. The
      injections into the DMH and PMD did not produce any significant effects on FPS.
      On the other hand, muscimol injections into the AHN and VMHDM caused significant
      reduction in FPS. These results indicate that injections of muscimol and
      semicarbazide into the DMH and PMD fail to change the FPS, whereas the
      enhancement of the GABA transmission in the AHN and VMHDM produces a reduction of
      the conditioned fear responses. On the other hand, the inhibition of this
      transmission led to an increase of this conditioned response in the AHN. Thus,
      whereas DMH and PMD are known to be part of the caudal-most region of the medial
      hypothalamic defensive system, which integrates unconditioned fear, systems
      mediating conditioned fear select the AHN and VMHDM nuclei that belong to the
      rostral-most portion of the hypothalamic defense area. Thus, distinct subsets of
      neurons in the hypothalamus could mediate different aspects of the defensive
      responses.

PMID- 18634895
TI  - Application of molecular techniques to evaluate the methanogenic archaea and
      anaerobic bacteria in the presence of oxygen with different COD:sulfate ratios in
      a UASB reactor.
AB  - In this paper, the microbial characteristics of the granular sludge in the
      presence of oxygen (3.0+/-0.7 mg O2 l(-1)) were analyzed using molecular biology
      techniques. The granules were provided by an upflow anaerobic sludge blanket
      (UASB) operated over 469 days and fed with synthetic substrate. Ethanol and
      sulfate were added to obtain different COD/SO4(2-) ratios (3.0, 2.0, and 1.6).
      The results of fluorescent in situ hybridization (FISH) analyses showed that
      archaeal cells, detected by the ARC915 probe, accounted for 77%, 84%, and 75% in
      the COD/SO(4)(2-) ratios (3.0, 2.0, and 1.6, respectively). Methanosaeta sp. was
      the predominant acetoclastic archaea observed by optical microscopy and FISH
      analyses, and confirmed by sequencing of the excised bands of the DGGE gel with a
      similarity of 96%. The sulfate-reducing bacterium Desulfovibrio vulgaris subsp.
      vulgaris (similarity of 99%) was verified by sequencing of the DGGE band. Others
      identified microorganism were similar to Shewanella sp. and Desulfitobacterium
      hafniense, with similarities of 95% and 99%, respectively. These results
      confirmed that the presence of oxygen did not severely affect the metabolism of
      microorganisms that are commonly considered strictly anaerobic. We obtained mean
      efficiencies of organic matter conversion and sulfate reducing higher than 74%.

PMID- 18634896
TI  - Probiotic properties of lactic acid bacteria isolated from stool samples of
      longevous people in regions of Hotan, Xinjiang and Bama, Guangxi, China.
AB  - A total of 567 lactic acid bacteria (LAB) strains were isolated from the stool
      samples of longevous people in regions of Hotan, Xinjiang and Bama, Guangxi,
      China. In order to reduce the number of strains for further examinations, 36
      isolates were screened out for further examination whilst the other strains,
      which had lower probiotic properties, were not suitable for yogurt production due
      to the absence of growth in pH 3.5 MRS medium and no curding during fermentation,
      and so were excluded. The result of identification by API, sequence analysis of
      16S rRNA and random amplified polymorphic DNA (RAPD) analysis showed that there
      were three strains of Lactobacillus acidophilus, 10 strains of Lactobacillus
      rhamnosus, three strains of Lactobacillus casein, three strains of Lactobacillus
      brevis, two strains of Enterococcus faecium, two strains of Enterococcus
      faecalis, four strains of Bifdibacterium infantis, three strains of
      Bifdibacterium brevise, three strains of Bifdibacterium bifidium, two strains of
      Bifdibacterium adolecentis and one strain of Bifdibacterium longam among the 36
      isolates. These strains were evaluated by in vitro methods including survival
      upon exposure to pH 2.0, 3.0 and/or 0.3% oxgall and adhesion to the human colon
      adenocarcinoma cell line Caco-2 as well as antimicrobial activity against
      potential pathogens. The results presented here show that L. rhamnosus LV108, L.
      rhamnosus F, B. brevise R39 and B. infantis R42 are acid and bile tolerant,
      adhere to the cultured human intestinal Caco-2 cell line, antagonistic activity
      against potential pathogenic bacteria infection in vitro, and so are potential
      strains for probiotic use.

PMID- 18634897
TI  - Injection of biogenic amines modulates osmoregulation of Litopenaeus vannamei:
      response of hemolymph osmotic pressure, ion concentration and osmolality
      effectors.
AB  - In this paper, we compared systematically the temporal and dose response
      relationship and physiological significance among biogenic amines injection,
      changes of ion concentration, FAA concentrations and composition and protein in
      context of osmoregulatory ability in marine euryhaline shrimp: Litopenaeus
      vannamei. The dopamine (DA) and 5-hydroxytryptamine (5-HT) injection all had
      transient effects on hemolymph osmolality, ion concentrations but which occurred
      in different time and were dose-dependent. The highest concentrations of FAAs in
      hemolymph of L. vannamei were alanine, glycine, argnine, proline, lysine which
      were considered to be specific osmotic effectors. Contrary to the reduction of
      hemocyanin, injection of DA 10(-6) mol shrimp(-1) and 5-HT 10(-6) mol shrimp(-1)
      induced notable protein increase respectively, which led to the rapid reduction
      of hemocyanin/protein ratio in range of 63.2% to 78.3%. The increase of hemolymph
      FAAs might come from the new amino acid synthesis or degradation of muscle
      protein to FAAs or denovo synthesis of FAAs. Our study showed that dopamine plays
      an important role in neurotransmission and causes osmoregulation response
      modulation and 5-HT has different activation mechanism on osmoregulation.

PMID- 18634898
TI  - Drosophila ia2 modulates secretion of insulin-like peptide.
AB  - Islet antigen-2 (IA-2) is a major autoantigen in type I diabetes. To throw light
      on the function of IA-2 we examined the role of ia2, a Drosophila homologue,
      during Drosophila development. In situ hybridization showed that ia2 was
      expressed in the central nervous system and midgut region. The neuronal
      expression pattern of ia2 was very similar to that of IA-2 in mammals. Disruption
      of gut-specific ia2 expression by double stranded RNA interference (dsRNAi)
      resulted in defects in gut development, and this phenotype was rescued by
      overexpression of hexokinase. Until now the roles of IA-2 and hexokinase in
      insulin signaling have been described separately but we found that ia2 modulated
      the expression of both insulin and hexokinase. Moreover this modulation seems to
      be important for gut development during metamorphosis. As the pancreas develops
      from the gut during vertebrate development, our results suggest a possible role
      of IA-2 in insulin and hexokinase regulation.

PMID- 18634899
TI  - The effect of inhibited replication on DNA migration in the comet assay in
      relation to cytotoxicity and clastogenicity.
AB  - The DNA-replication inhibitors aphidicolin (APC) and hydroxyurea (HU) were tested
      for their ability to induce effects on DNA in the in vitro alkaline comet assay
      with V79 cells. APC concentrations up to 15 microM and HU concentrations up to
      500 microM did not significantly increase the extent of DNA migration after
      treatment during 4h. Treatment for 18 h, however, led to inconsistently
      significant increase in DNA migration. These increases in DNA migration were
      accompanied by severe cell-cycle disturbances, cytotoxic effects (reduced
      population doubling and reduced mitotic index) and increased frequencies of cells
      with chromosome aberrations. The results indicate that substances with such
      secondary effects on DNA (in contrast to agents that directly damage DNA) only
      induce effects in the comet assay after prolonged exposure, together with
      cytotoxic effects. We conclude that slight inhibition of DNA replication and cell
      cycle delay per se do not cause significant effects in the in vitro comet assay
      under standard test conditions. Furthermore, the in vitro comet assay seems to be
      less sensitive towards this type of secondary DNA effects than the in vitro
      chromosome aberration test.

PMID- 18634900
TI  - Identification of a new mutagen, 4,4'-diamino-3,3'-dichloro-5-nitrobiphenyl, in
      river water flowing through an industrial area in Wakayama, Japan.
AB  - 3,3'-Dichlorobenzidine (DCB), which has been assigned as a possible carcinogen to
      humans (Group 2B) by IARC, is produced as a raw material in the manufacture of
      polymers and dye intermediates. In our previous paper, we identified DCB as an
      indirect-acting mutagenic constituent in the water concentrates from the Waka
      River, which flows through an industrial area in Wakayama, Japan. In this study,
      we have identified a novel mutagen in the water samples from the Waka River.
      Organic chemicals in the river water were adsorbed to blue rayon at the site
      where effluents from chemical plants and a sewage plant were discharged into the
      river. The adsorbate was highly mutagenic in Salmonella YG1024 in the presence
      and absence of S9 mix, inducing 440,000 and 170,000 revertants/g blue rayon
      equivalent, respectively. Two mutagenic fractions, which accounted for 18% and
      12% of the total mutagenicity of the water concentrate in YG1024 with S9 mix,
      were separated by HPLC with a reversed-phase column following Sephadex LH20
      column chromatography. Both fractions were further separated by HPLC using
      reversed-phase columns. On the basis of spectral analysis and co-chromatography
      using an authentic chemical standard, one mutagen in the former fraction was
      identified as DCB and one mutagen in the latter fraction was deduced to be a
      novel chemical, a 5-nitro derivative of DCB (5-nitro-DCB; 4,4'-diamino-3,3'
      dichloro-5-nitrobiphenyl). 5-Nitro-DCB showed strong mutagenicity in YG1024
      especially with S9 mix, inducing 24,200 revertants/microg. 5-Nitro-DCB was
      detected in water concentrates in the range from less than detection limit to 6.9
      microg/g of blue rayon. DCB was also detected in the range from 13.2 to 104
      micro/g of blue rayon. These results demonstrate that Waka River water might be
      continually contaminated with the indirect-acting mutagens DCB and 5-nitro-DCB as
      major mutagenic constituents of the river water.

PMID- 18634901
TI  - Spontaneous worm expulsion and intestinal IgA response in mice infected by
      Vampirolepis nana.
AB  - The expulsion of the gastrointestinal parasite Vampirolepis nana was examined in
      different mouse strains and in immunosuppressed mice infected to different
      degrees with eggs and cysticercoids. To investigate the immunological mechanism
      that regulates expulsion, surface-bound mouse immunoglobulins were examined on
      adult worms. The time to spontaneous expulsion of worms was dependent on strain
      (C57BL, BDF(1), B6C3F(1)<BALB/c<CBA<DBA/2<C3H; all male mice) and on the degree
      of infection. In mice given immunosuppressants, the expulsion of worms was
      prevented completely. Immunoenzyme methods showed that IgA was the only
      detectable surface-bound antibody found on worms obtained from the intestines of
      mice of various strains throughout the course of infection. There was no evidence
      of surface-bound immunoglobulins on adult worms obtained from immunosuppressed
      mice. There was a good temporal correlation between the time-course of expulsion
      and the appearance of IgA. The data suggest that the expulsion of V. nana is
      closely associated with the appearance of parasite-specific IgA.

PMID- 18634902
TI  - n-3 fatty acids (eicosapentanoic and docosahexanoic acids) in epilepsy and for
      the prevention of sudden unexpected death in epilepsy.

PMID- 18634903
TI  - Cortisol response to acute stress in jundia Rhamdia quelen acutely exposed to sub
      lethal concentrations of agrichemicals.
AB  - Exposure to agrichemicals can have deleterious effects on fish, such as
      disruption of the hypothalamus-pituitary-inter-renal axis (HPI) that could impair
      the ability of fish to respond to stressors. In this study, fingerlings of the
      teleost jundia (Rhamdia quelen) were used to investigate the effects of the
      commonly used agrichemicals on the fish response to stress. Five common
      agrichemicals were tested: the fungicide - tebuconazole, the insecticide - methyl
      parathion, and the herbicides - atrazine, atrazine+simazine, and glyphosate.
      Control fishes were not exposed to agrichemicals and standard stressors. In
      treatments 2-4, the fishes were exposed to sub-lethal concentrations (16.6%,
      33.3%, and 50% of the LC(50)) of each agrichemical for 96 h, and at the end of
      this period, were subjected to an acute stress-handling stimulus by chasing them
      with a pen net. In treatments 5-7 (16.6%, 33.3%, and 50% of the LC(50)), the
      fishes were exposed to the same concentrations of the agrichemicals without
      stress stimulus. Treatment 8 consisted of jundias not exposed to agrichemicals,
      but was subjected to an acute stress-handling stimulus. Jundias exposed to methyl
      parathion, atrazine+simazine, and glyphosate presented a decreased capacity in
      exhibiting an adequate response to cope with stress and in maintaining the
      homeostasis, with cortisol level lower than that in the control fish (P<0.01). In
      conclusion, the results of this study clearly demonstrate that the acute exposure
      to sub-lethal concentrations of methyl-parathion, atrazine+simazine, and
      glyphosate exert a deleterious effect on the cortisol response to an additional
      acute stressor in the jundia fingerlings.

PMID- 18634904
TI  - Genetic heterogeneity of Wuchereria bancrofti populations at spatially
      hierarchical levels in Pondicherry and surrounding areas, south India.
AB  - Lymphatic filariasis (LF), caused by Wuchereria bancrofti is widely distributed
      in areas of India with variable geoclimatic factors. These factors, coupled with
      chemotherapeutic pressure exerted for past half a century may have influenced the
      genetic structure of the parasite populations. A complex genetic structure of
      parasite populations will have major consequences to the on-going global LF
      elimination programme. Hence, it is of interest to understand the genetic
      heterogeneity of W. bancrofti parasite populations. We studied the genetic
      heterogeneity of populations of W. bancrofti populations from mf carriers
      residing in an urban area of Pondicherry and surrounding villages through
      molecular (RAPD) fingerprinting. The analysis showed that W. bancrofti
      populations of an urban area were mostly highly heterogeneous, while those of
      rural areas were homogenous. The urban parasite populations appeared to be a pool
      of parasite population originating from surrounding rural areas. At least two
      genotypes, exhibiting high genetic differentiation and minimum gene flow between
      them, existed in Pondicherry urban areas. There was a minimum gene flow between
      parasite populations of villages. The genetic heterogeneity of parasite
      population in an adult microfilariae carrier was significantly high, possibly due
      to accumulation of different genotypes of the parasite with increasing age. The
      genetic heterogeneity of W. bancrofti populations in an individual mf carrier, in
      urban and rural areas, within an endemic area at large, and in different
      geographical regions of India may have far reaching implications to the
      epidemiology and strategies of chemotherapy control being adopted for LF
      elimination programme launched on a global scale.

PMID- 18634907
TI  - Noradrenergic modulation of the respiratory neural network.
AB  - Noradrenergic dysregulation has been reported in human pathologies affecting the
      control of breathing, such as sudden infant death syndrome, congenital central
      hypoventilation syndrome and Rett syndrome. Noradrenergic neurons, located
      predominantly in pontine nuclei, are among the earliest to arise within the
      hindbrain and play an essential role in the maturation of the respiratory
      network. Noradrenergic neurons also play a major role in the modulation of the
      respiratory motor pattern from birth through adulthood. The critical importance
      of this signaling system in respiratory control is illustrated by the severe
      respiratory disturbances associated with gene mutations affecting noradrenergic
      neurons (Phox2 and Mecp2). Here, the role of catecholaminergic pontine nuclei in
      the control of breathing, the cellular effects of norepinephrine on the
      respiratory network and the pathological consequence to breathing of
      abnormalities in this signaling system will be discussed.

PMID- 18634906
TI  - Cell-type-specific consequences of nucleotide excision repair deficiencies:
      Embryonic stem cells versus fibroblasts.
AB  - Pluripotent embryonic stem cells (ES cells) are the precursors of all different
      cell types comprising the organism. Since persistent DNA damage in this cell type
      might lead to mutations that cause huge malformations in the developing organism,
      genome caretaking is of prime importance. We first compared the sensitivity of
      wild type mouse embryonic fibroblasts (MEFs) and ES cells for various genotoxic
      agents and show that ES cells are more sensitive to treatment with UV-light,
      gamma-rays and mitomycin C than MEFs. We next investigated the contribution of
      the transcription-coupled (TC-NER) and global genome (GG-NER) sub-pathways of
      nucleotide excision repair (NER) in protection of ES cells, using cells from
      mouse models for the NER disorders xeroderma pigmentosum (XP) and Cockayne
      syndrome (CS). TC-NER-deficient Csb(-/-) and GG-NER/TC-NER-defective Xpa(-/-)
      MEFs are hypersensitive to UV, whereas GG-NER-deficient Xpc(-/-) MEFs attribute
      intermediate UV sensitivity. The observed UV-hypersensitivity in Csb(-/-) and
      Xpa(-/-) MEFs correlates with increased apoptosis. In contrast, Xpa(-/-) and Xpc(
      /-) ES cells are highly UV-sensitive, while a Csb deficiency only causes a mild
      increase in UV-sensitivity. Surprisingly, a UV-induced hyperapoptotic response is
      mainly observed in Xpa(-/-) ES cells, suggesting a different mechanism of
      apoptosis induction in ES cells, mainly triggered by damage in the global genome
      rather than in transcribed genes (as in MEFs). Moreover, we show a pronounced S
      phase delay in Xpa(-/-) and Xpc(-/-) ES cells, which might well function as a
      safeguard mechanism for heavily damaged ES cells in case the apoptotic response
      fails. Although Xpa(-/-) and Xpc(-/-) ES cells are totally NER-defective or GG
      NER-deficient respectively, mutation induction upon UV is similar compared to
      wild type ES cells indicating that the observed apoptotic and cell cycle
      responses are indeed sufficient to protect against proliferation of damaged
      cells. In conclusion, we show a double safeguard mechanism in ES cells against
      NER-type of damages, which mainly relies on damage detection in the global
      genome.

PMID- 18634905
TI  - Reduced efficiency and increased mutagenicity of translesion DNA synthesis across
      a TT cyclobutane pyrimidine dimer, but not a TT 6-4 photoproduct, in human cells
      lacking DNA polymerase eta.
AB  - Xeroderma pigmentosum variant (XPV) patients carry germ-line mutations in DNA
      polymerase eta (poleta), a major translesion DNA synthesis (TLS) polymerase, and
      exhibit severe sunlight sensitivity and high predisposition to skin cancer. Using
      a quantitative TLS assay system based on gapped plasmids we analyzed TLS across a
      site-specific TT CPD (thymine-thymine cyclobutane pyrimidine dimer) or TT 6-4 PP
      (thymine-thymine 6-4 photoproduct) in three pairs of poleta-proficient and
      deficient human cells. TLS across the TT CPD lesion was reduced by 2.6-4.4-fold
      in cells lacking poleta, and exhibited a strong 6-17-fold increase in mutation
      frequency at the TT CPD. All targeted mutations (74%) in poleta-deficient cells
      were opposite the 3'T of the CPD, however, a significant fraction (23%) were semi
      targeted to the nearest nucleotides flanking the CPD. Deletions and insertions
      were observed at a low frequency, which increased in the absence of poleta,
      consistent with the formation of double strand breaks due to defective TLS. TLS
      across TT 6-4 PP was about twofold lower than across CPD, and was marginally
      reduced in poleta-deficient cells. TLS across TT 6-4 PP was highly mutagenic (27
      63%), with multiple mutations types, and no significant difference between cells
      with or without poleta. Approximately 50% of the mutations formed were semi
      targeted, of which 84-93% were due to the insertion of an A opposite the template
      G 5' to the 6-4 PP. These results, which are consistent with the UV hyper
      mutability of XPV cells, highlight the critical role of poleta in error-free TLS
      across CPD in human cells, and suggest a potential involvement, although minor,
      of poleta in TLS across 6-4 PP under some conditions.

PMID- 18634908
TI  - Receptor tyrosine kinases and respiratory motor plasticity.
AB  - Protein kinases are a family of enzymes that transfer a phosphate group from
      adenosine tri-phosphate to an amino acid residue on a protein. The receptor
      tyrosine kinases (RTKs) are expressed on the outer cell membrane, bind
      extracellular protein ligands, and phosphorylate tyrosine residues on other
      proteins-essentially permitting communication between cells. Such activity
      regulates multiple aspects of cellular physiology including cell growth and
      differentiation, adhesion, motility, cell death, and morphological and synaptic
      plasticity. This review will focus on the role of RTKs in respiratory motor
      plasticity, with particular emphasis on long-term changes in respiratory
      motoneuron function. Reflecting the predominant literature, specific attention
      will be devoted to the role of tropomyosin-related kinase type B (TrkB)
      activation on phrenic motoneuron activity. However, many RTKs share similar
      patterns of expression and mechanisms of ligand-induced activation and downstream
      signaling. Thus, a perspective based on TrkB-induced phrenic motor plasticity may
      provide insight into the potential roles of other RTKs in the neural control of
      breathing. Finally, understanding how different RTKs affect respiratory motor
      output in the long-term may provide future avenues for pharmacological
      development with the goal of increasing respiratory motor output in disorders
      such as obstructive sleep apnea and after spinal cord injury. This is best
      illustrated in recent studies where we have used small, highly diffusible
      molecules to transactivate TrkB receptors near phrenic motoneurons to improve
      breathing after cervical spinal cord injury.

PMID- 18634910
TI  - Two-dimensional gel electrophoresis of wool intermediate filament proteins.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) methods have been
      used to provide high-resolution separation of wool intermediate filament proteins
      (IFPs). An improved method of extraction was developed based on a previously
      published method. The improved method for extraction eliminates the use of
      dialysis and freeze-drying between the extraction and rehydration steps, allowing
      the extraction and rehydration for the first dimension gel to be achieved in one
      day. Improvements to the method for maintaining reducing conditions and chaotrope
      constitution, combined with low %T polyacrylamide gels, allowed the high
      resolution separation of the two keratin IFP families and their individual family
      members. The IFPs were separated to produce a clearly defined spot pattern of
      higher intensity, with numerous minor spots not previously observed, and a marked
      improvement in the vertical resolution. Further work to analyse the composition
      of each of the protein spots has been made much easier by being able to separate
      the IFPs into discrete spots.

PMID- 18634909
TI  - Structural and kinetic properties of Bacillus subtilis S-adenosylmethionine
      synthetase expressed in Escherichia coli.
AB  - S-adenosylmethionine (SAM) synthetase (EC 2.5.1.6) catalyzes the synthesis of S
      adenosylmethionine using l-methionine and ATP as substrates. SAM synthetase gene
      (metE) from Bacillus subtilis was cloned and over-expressed, for the first time,
      in the heterologus host Escherichia coli as an active enzyme. Size-exclusion
      chromatography (SEC) revealed a molecular weight of ~180 kDa, suggesting that the
      enzyme is a homotetramer stabilized by non-covalent interactions. SAM synthetase
      exhibited optimal activity at pH 8.0 and 45 degrees C with the requirement of
      divalent cation Mg(2+), and stimulated by the monovalent cation K(+). The enzyme
      followed sequential mechanism with a V(max) of 0.362 micromol/min/mg, and a K(m)
      of 920 microM and 260 microM for ATP and l-methionine, respectively. The urea
      induced unfolding equilibrium of the recombinant enzyme revealed a multistate
      process, comprising partially unfolded tetramer, structural dimer, structural
      monomer and completely unfolded monomer, as evidenced by intrinsic and extrinsic
      fluorescence, circular dichroism (CD) and SEC. Absence of trimer in the SEC
      implicates that the enzyme is a dimer of dimer. Concordance between results of
      SEC and enzyme activity in the presence of urea amply establishes that tetramer
      alone with intersubunit active site(s) exhibits enzyme activity.

PMID- 18634911
TI  - Analysis of the transcriptional regulation of the FABP2 promoter haplotypes by
      PPARgamma/RXRalpha and Oct-1.
AB  - Variants of the human intestinal fatty acid binding protein 2 gene (FABP2) are
      associated with traits of the metabolic syndrome. Relevant FABP2 promoter
      polymorphisms c.-80_-79insT, c.-136_-132delAGTAG, c.-168_-166delAAGinsT, c.
      260G>A, c.-471G>A, and c.-778G>T result in two haplotypes A and B. Activation of
      haplotypes by rosiglitazone stimulated PPARgamma/RXRalpha leads to 2-fold higher
      activity of haplotype B than A. As shown by chimeric FABP2 promoter constructs,
      the higher responsiveness of FABP2 haplotype B is mainly but not solely
      determined by polymorphism c.-471G>A. As shown by EMSA and promoter-reporter
      assays, Oct-1 interacts with the -471 region of FABP2 promoters, induces the
      activities of both FABP2 promoter haplotypes and abolishes the different
      activities of haplotypes induced by rosiglitazone activated PPARgamma/RXRalpha.
      In conclusion, our findings suggest a functional role of PPARgamma/RXRalpha and
      Oct-1 in the regulation of the FABP2 gene.

PMID- 18634912
TI  - Monitoring miRNA-mediated silencing in Drosophila melanogaster S2-cells.
AB  - MicroRNAs (miRNAs) are small cellular RNAs that participate in post
      transcriptional gene regulation. Even though they were only recently discovered,
      research on the biogenesis, mechanism of repression and biological significance
      of miRNAs has already received much attention. In this study, we have compared
      expression strategies for miRNA-activity reporter constructs and have examined
      the dependence of silencing by a particular Drosophila miRNA, bantam, on specific
      argonaute proteins. Consistent with previous biochemical experiments, we found
      that bantam silencing is strongly dependent on Ago1, but in addition we could
      detect the activity of Ago2-loaded bantam. Our experiments suggest that a
      perfectly complementary design and a transient expression strategy for reporter
      constructs may--in the case of catalytically active Ago-proteins--lead to a
      disproportionately strong response mediated by a minor fraction of silencing
      complexes. We present evidence that Drosophila S2-cells of independent sources
      differ in their RNAi efficiency in response to dsRNA added to the growth medium,
      and that the selection antibiotic G418 acts as an inhibitor of RNAi induced by
      soaking.

PMID- 18634913
TI  - Pressure, oxygen tension and temperature in the periosteal callus during bone
      healing--an in vivo study in sheep.
AB  - Adequate blood supply and sufficient mechanical stability are necessary for
      timely fracture healing. Damage to vessels impairs blood supply; hindering the
      transport of oxygen which is an essential metabolite for cells involved in
      repair. The degree of mechanical stability determines the mechanical conditions
      in the healing tissues. The mechanical conditions can influence tissue
      differentiation and may also inhibit revascularization. Knowledge of the actual
      conditions in a healing fracture in vivo is extremely limited. This study aimed
      to quantify the pressure, oxygen tension and temperature in the external callus
      during the early phase of bone healing. Six Merino-mix sheep underwent a tibial
      osteotomy. The tibia was stabilized with a standard mono-lateral external
      fixator. A multi-parameter catheter was placed adjacent to the osteotomy gap on
      the medial aspect of the tibia. Measurements of oxygen tension and temperature
      were performed for ten days post-op. Measurements of pressure were performed
      during gait on days three and seven. The ground reaction force and the
      interfragmentary movements were measured simultaneously. The maximum pressure
      during gait increased (p=0.028) from three (41.3 [29.2-44.1] mm Hg) to seven days
      (71.8 [61.8-84.8] mm Hg). During the same interval, there was no change (p=0.92)
      in the peak ground reaction force or in the interfragmentary movement
      (compression: p=0.59 and axial rotation: p=0.11). Oxygen tension in the haematoma
      (74.1 mm Hg [68.6-78.5]) was initially high post-op and decreased steadily over
      the first five days. The temperature increased over the first four days before
      reaching a plateau at approximately 38.5 degrees C on day four. This study is the
      first to report pressure, oxygen tension and temperature in the early callus
      tissues. The magnitude of pressure increased even though weight bearing and IFM
      remained unchanged. Oxygen tensions were initially high in the haematoma and fell
      gradually with a low oxygen environment first established after four to five
      days. This study illustrates that in bone healing the local environment for cells
      may not be considered constant with regard to oxygen tension, pressure and
      temperature.

PMID- 18634914
TI  - Brugada syndrome.
AB  - Since its first description in 1992 as a new clinical entity, the Brugada
      syndrome has aroused great interest among physicians and basic scientists. Two
      consensus conferences held in 2002 and 2005 helped refine the current accepted
      definite diagnostic criteria for the syndrome, briefly, the characteristic ECG
      pattern (right bundle branch block and persistent ST segment elevation in right
      precordial leads) together with the susceptibility for ventricular fibrillation
      and sudden death. In the last years, clinical and basic research have provided
      very valuable knowledge on the genetic basis, the cellular mechanisms responsible
      for the typical ECG features and the electrical susceptibility, the clinical
      particularities and modulators, the diagnostic value of drug challenge, the risk
      stratification of sudden death (possibly the most controversial issue) and,
      finally, the possible therapeutic approaches for the disease. Each one of these
      points is discussed in this review, which intends to provide updated information
      supplied by recent clinical and basic studies.

PMID- 18634915
TI  - Catecholaminergic polymorphic ventricular tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly
      malignant form of arrhythmogenic disorder characterized by exercise- or emotional
      induced polymorphic ventricular tachycardia in the absence of detectable
      structural heart disease. Because of the typical pattern of arrhythmias
      (bidirectional ventricular tachycardia and the occurrence and severity of
      arrhythmia correlated well with exercise workload) during exercise stress test,
      CPVT can be identified promptly. Molecular genetic screening of the genes
      encoding the cardiac ryanodine receptor and calsequestrin is critical to confirm
      uncertain diagnosis of CPVT. With the exception of beta-blockers, no
      pharmacologic therapy of proven effectiveness is available: although beta
      blockers reduce the occurrence of ventricular tachycardia, 30% of patients
      treated with beta-blockers still experience cardiac arrhythmias and eventually
      require implantable cardioverter defibrillator implantation to prevent cardiac
      arrest.

PMID- 18634916
TI  - Arrhythmogenic right ventricular dysplasia.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy
      characterized by ventricular arrhythmias and structural abnormalities of the
      right ventricle (RV). ARVD results from progressive replacement of right
      ventricular myocardium with fatty and fibrous tissue. The precise prevalence of
      ARVD in the United States has been estimated to be 1 in 5000 of the general
      population. Recent evidence has made it clear that ARVD is a disease of
      desmosomal dysfunction. The main management consideration concerns whether to
      implant an ICD. Catheter ablation of VT is a largely a paliative procedure that
      should not be considered as an appropriate strategy to eliminate VT or reduce
      sudden death risk. It is likely that the recent advances in the understanding of
      the pathophysiologic basis of this condition will result in more targeted
      treatment approaches in the future.

PMID- 18634917
TI  - Sudden cardiac death in athletes.
AB  - Sudden cardiac death in athletes is an uncommon but extremely visible event
      because of the high profile of amateur and professional athletes and the expected
      excellent health of these athletes. However, paradoxically, athletic performance
      may immediately increase the risk of ventricular arrhythmias and sudden cardiac
      death while run reducing atherosclerosis, which thus improves cardiovascular
      health and longevity. In athletes younger than 30 years, the most common
      underlying causes are due to inherited heart disease. In the older athletes,
      sudden death is generally due to arrhythmias in the context of coronary artery
      disease. Many athletes with aborted sudden death, arrhythmia-related syncope, or
      high-risk genetic disorders benefit from therapy with implanted
      cardioverter/defibrillators (ICDs) . Although ICD therapy can effectively abort
      sudden death, implantation of an ICD generally prohibits an individual from all
      competitive athletics except low-intensity sports. The screening of athletes has
      been notoriously inadequate; however, the optimal screening strategies have yet
      to be determined. Recommendations for participation in competitive athletics
      generally follow the recently published 36th Bethesda Conference Eligibility
      Recommendations for Competitive Athletes with Cardiovascular Abnormalities.

PMID- 18634918
TI  - Sudden cardiac death in infiltrative cardiomyopathies: sarcoidosis, scleroderma,
      amyloidosis, hemachromatosis.
AB  - Sarcoidosis, scleroderma, amyloidosis, and hemachromatosis are systemic
      infiltrative disorders that commonly affect the heart. Owing to their potential
      for diffuse organ involvement, these diseases may present with myriad clinical
      manifestations. Conduction system abnormalities are common, and each of these
      disorders has been associated with sudden cardiac death. In this review, we
      summarize the epidemiology, clinical features, diagnosis, and treatment of each
      of these entities. We place special emphasis on existing literature as it
      pertains to risk stratification and therapy aimed at the prevention of sudden
      cardiac death in these infiltrative cardiomyopathies.

PMID- 18634920
TI  - Global health assistance for chronic illness: a look at the practical.
AB  - The changing pattern of disease in the developing world calls for a change in the
      structure, goals, and personnel of global health assistance. Chronic diseases are
      now the dominant threat to health and are becoming a challenge to economic
      advancement in developing economies. Because confronting these diseases, heart
      disease and diabetes mellitus in particular, requires long-tem, ongoing programs,
      the support and funding must come from within and therefore must reflect a
      nation's commitment to combat them. One model for this change is a 3-legged stool
      or platform upon which an assault on chronic disease can be built. The 3 legs are
      (1) an effective primary health care delivery system, (2) effective health
      promotion, and (3) a macroeconomic repositioning of health within the government
      bureaucracy and the world of commerce. To construct each of these legs requires
      changes in the structure and roles of global health assistance organizations.

PMID- 18634919
TI  - Metabolic reserve of the heart: the forgotten link between contraction and
      coronary flow.
AB  - Myocardial energy substrate metabolism entails a complex system of enzyme
      catalyzed reactions, in which the heart efficiently converts chemical to
      mechanical energy. The system is highly regulated and responsive to changes in
      workload as well as in substrate and hormone supply to the heart. Akin to the
      terms "contractile reserve" and "coronary flow reserve" we propose the term
      "metabolic reserve" to reflect the heart's capacity to respond to increases in
      workload. The heart's metabolic response to inotropic stimulation involves the
      ability to increase oxidative metabolism over a wide range, by activating the
      oxidation of glycogen and carbohydrate substrates. Here we review the known
      biochemical mechanisms responsible for those changes. Specifically, we explore
      the notion that disturbances in the metabolic reserve result in contractile
      dysfunction of the stressed heart.

PMID- 18634921
TI  - Efficacy of revascularization to induce apexification/apexogensis in infected,
      nonvital, immature teeth: a pilot clinical study.
AB  - Endodontic treatment options for immature, nonvital teeth conventionally include
      surgical endodontics, apexification with calcium hydroxide, or single visit
      mineral trioxide aggregate plug. A new treatment option of revascularization has
      recently been introduced. It involves disinfecting the root canal system,
      providing a matrix of blood clot into which cells could grow, and sealing of the
      coronal access. The present pilot clinical study was undertaken to evaluate the
      efficacy of revascularization in 14 cases of infected, immature teeth. Endodontic
      treatment was initiated, and after infection control, revascularization was
      performed. The access cavity was sealed with glass ionomer cement. The cases were
      followed up at regular intervals of 3 months; the range in follow-up was 0.5-3.5
      years. The outcomes were as follows. Radiographic resolution of periradicular
      radiolucencies was judged to be good to excellent in 93% (13 of 14) of the cases.
      In the majority of cases, a narrowing of the wide apical opening was evident. In
      3 cases, thickening of apical dentinal walls and increased root length were
      observed. The striking finding was complete resolution of clinical signs and
      symptoms and appreciable healing of periapical lesions in 78% (11 of 14) of
      cases. Thickening of lateral dentinal walls was evident in 57% (8/14) of cases,
      and increased root length was observed in 71% (10/14) of cases. None of the cases
      presented with pain, reinfection, or radiographic enlargement of preexisting
      apical pathology. This pilot study documented a favorable outcome of
      revascularization procedures conducted in immature nonvital, infected permanent
      teeth.

PMID- 18634922
TI  - Microorganisms in root canal-treated teeth from a German population.
AB  - Posttreatment apical periodontitis is usually associated with persistent or
      secondary intraradicular infection. This study evaluated the presence and
      relative levels of 28 bacterial taxa in treated root canals of teeth with
      posttreatment apical periodontitis from German patients using 16S ribosomal RNA
      (rRNA) gene probes in a reverse-capture checkerboard hybridization assay. Species
      specific polymerase chain reaction (PCR) was also performed to detect
      Enterococcus faecalis and Candida albicans. Bacterial DNA was detected in all
      samples. Twenty of the 28 taxon-specific probes tested were reactive with at
      least one sample. Taxa detected more frequently included Streptococcus species
      (47%), Lactobacillus species (35%), Dialister invisus (29%), Eubacterium infirmum
      (29%), Prevotella intermedia (29%), Selenomonas sputigena (29%), Synergistes oral
      clone BA121 (29%), and Treponema denticola (29%). Only eight taxa were present at
      levels >10(5). Of these, streptococci and T. denticola were the most prevalent.
      Species-specific PCR detected E. faecalis in 47% of the cases and C. albicans in
      6%. Findings of this study confirm the strong association between
      persistent/secondary intraradicular infection and posttreatment apical
      periodontitis. Most cases harbored a mixed infection, and E. faecalis, if
      present, was never the most dominant species in the consortium. Several other
      bacterial taxa were detected, and an involvement with the etiology of
      posttreatment apical periodontitis is suspected.

PMID- 18634923
TI  - Differential patterns of receptor activator of nuclear factor kappa B
      ligand/osteoprotegerin expression in human periapical granulomas: possible
      association with progressive or stable nature of the lesions.
AB  - Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin
      (OPG) are expressed in apical periodontitis, suggesting a role for these
      molecules during lesion development. However, the profiles of RANKL/OPG
      expression in periapical lesions remain unknown. In this study we investigated
      the patterns of RANKL and OPG mRNA expression by real-time polymerase chain
      reaction in human periapical granulomas (N = 44) and compared them with sites
      presenting characteristic bone resorbing activity: healthy (n = 14) and
      orthodontically stretched and compressed periodontal ligament (n = 26), healthy
      gingiva (n = 24), chronic gingivitis (n = 32), and chronic periodontitis (n = 34)
      samples. Both RANKL and OPG mRNA expression was higher in periapical granulomas
      when compared with healthy periodontal ligament. Distinct patterns of RANKL and
      OPG expression ratio were found in the granulomas and in different physiologic
      and pathologic conditions, with characteristic bone resorption activity
      potentially being indicative of the stable or progressive nature of the lesions.
      Lesions with radiographic image smaller than 5 mm showed higher RANKL/OPG
      expression than images greater than 5 mm. Periapical granulomas presented
      heterogeneous patterns of RANKL and OPG expression, ranging from samples with
      RANKL/OPG ratio similar to that seen in sites with minimal or absent bone
      resorption to samples with RANKL/OPG expression pattern comparable with active
      bone resorption sites.

PMID- 18634924
TI  - The expression and role of stromal cell-derived factor-1alpha-CXCR4 axis in human
      dental pulp.
AB  - Recent reports have suggested that the stromal cell-derived factor (SDF)-1alpha
      CXCR4 axis has a direct effect on stem and progenitor cell recruitment in muscle
      and neural tissue repair after injury. No information is available about SDF
      1alpha or CXC chemokine receptor 4 (CXCR4) in dental tissues. The aim of this
      study was to assess the expression of SDF-1alpha and its receptor, CXCR4, in
      healthy or inflamed human dental pulp and to evaluate the effects of SDF-1alpha
      on dental pulp cells (DPCs) in both proliferation and migration in vitro.
      Immunohistochemical staining and reverse-transcription polymerase chain reaction
      detected weak expression of SDF-1alpha and CXCR4 in healthy dental pulp and
      strong expression of SDF-1alpha and CXCR4 in inflamed dental pulp. A
      methylthiazol tetrazolium assay showed that SDF-1alpha could not promote DPCs
      proliferation. A transmigration assay, however, indicated that SDF-1alpha
      enhanced DPCs migration, which could be abolished by anti-CXCR4 antibodies. Taken
      together, these results imply that the SDF-1alpha-CXCR4 axis may play a role in
      the recruitment of CXCR4-positive DPCs toward the damaged sites.

PMID- 18634925
TI  - Calcitonin gene-related peptide receptor expression in alternatively activated
      monocytes/macrophages during irreversible pulpitis.
AB  - The purpose of this study was to quantify the percentage and the mean
      fluorescence intensity of viable alternatively activated monocytes/macrophages
      (AAMo) CD163+ positive for calcitonin gene-related peptide receptor (CGRPr)
      within the total AAMo population in human dental pulp. Pulp tissue samples were
      collected from teeth with a clinical diagnosis of irreversible pulpitis (n = 13),
      pulps with induced inflammation (n = 13), and normal pulps (n = 13). All samples
      were labeled to identify positive cells for CGRPr and CD163 using a flow
      cytometry assay. Results demonstrated that a high percentage of total viable AAMo
      CD163+ expressed CGRPr on their membranes (72.12% in healthy pulp, 62.20% in
      irreversible pulpitis, and 58.01% in induced pulpitis). Significant differences
      were found between mean AAMo CD163+ fluorescence for CGRPr according to pulp
      condition, being greater in irreversible pulpitis. It can be concluded that AAMo
      CD163+ are expressed during normal and inflammatory processes, supporting the
      hypothesis that they could exercise an anti-inflammatory action that could be
      controlled by CGRP signaling after its binding.

PMID- 18634926
TI  - A Comparison of four pulpotomy techniques in primary molars: a long-term follow
      up.
AB  - The study evaluated the effects of formocresol (FC), ferric sulphate (FS),
      calcium hydroxide (Ca[OH](2)), and mineral trioxide aggregate (MTA) as pulp
      dressing agents in pulpotomized primary molars. Sixteen children each with at
      least four primary molars requiring pulpotomy were selected. Eighty selected
      teeth were divided into four groups and treated with one of the pulpotomy agent.
      The children were recalled for clinical and radiographic examination every 6
      months during 2 years of follow-up. Eleven children with 56 teeth arrived for
      clinical and radiographic follow-up evaluation at 24 months. The follow-up
      evaluations revealed that the success rate was 76.9% for FC, 73.3% for FS, 46.1%
      for Ca(OH)(2), and 66.6% for MTA. In conclusion, Ca(OH)(2)is less appropriate for
      primary teeth pulpotomies than the other pulpotomy agents. FC and FS appeared to
      be superior to the other agents. However, there was no statistically significant
      difference between the groups.

PMID- 18634927
TI  - Root form and canal morphology of Jordanian maxillary first premolars.
AB  - This study was conducted to investigate root canal morphology of maxillary first
      premolars in a Jordanian population. Six hundred maxillary first premolars were
      collected, stained, and decalcified. Cleared teeth were examined and the
      following features were evaluated: (1) number of roots, (2) presence of furcation
      grooves, (3) location of apical foramina, (4) number and types of root canal, (5)
      number of lateral canals and isthmi, and (6) frequency of apical deltas. Of the
      six hundred maxillary first premolars 30.8% has one root, 63.2% has two, and 5.2%
      has bifid roots. Concerning root canal morphology, 79.7% had two canals with two
      separate apical foramina, whereas 3.3% of the teeth possessed type I canal
      systems. All two rooted maxillary first premolars showed furcation groove in the
      buccal roots. Maxillary first premolars are mainly two rooted and mostly have two
      canals. The presence of furcation groove should be kept in mind during both
      endodontic and prosthodontic procedures.

PMID- 18634928
TI  - Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth.
AB  - Stem cells from human exfoliated deciduous teeth (SHED) have been isolated and
      characterized as multipotent cells. However, it is not known whether SHED can
      generate a dental pulp-like tissue in vivo. The purpose of this study was to
      evaluate morphologic characteristics of the tissue formed when SHED seeded in
      biodegradable scaffolds prepared within human tooth slices are transplanted into
      immunodeficient mice. We observed that the resulting tissue presented
      architecture and cellularity that closely resemble those of a physiologic dental
      pulp. Ultrastructural analysis with transmission electron microscopy and
      immunohistochemistry for dentin sialoprotein suggested that SHED differentiated
      into odontoblast-like cells in vivo. Notably, SHED also differentiated into
      endothelial-like cells, as demonstrated by B-galactosidase staining of cells
      lining the walls of blood-containing vessels in tissues engineered with SHED
      stably transduced with LacZ. This work suggests that exfoliated deciduous teeth
      constitute a viable source of stem cells for dental pulp tissue engineering.

PMID- 18634929
TI  - Immunohistochemical analysis of nestin, osteopontin, and proliferating cells in
      the reparative process of exposed dental pulp capped with mineral trioxide
      aggregate.
AB  - This study investigated the reparative process of mechanically exposed pulps
      capped with mineral trioxide aggregate (MTA). Maxillary first molars of 8-week
      old rats were MTA-capped for 1-14 days, and 5-bromo-2'-deoxyuridine-labeled
      proliferating cells and immunoreactivity for nestin and osteopontin were
      analyzed. MTA capping caused mild necrotic changes followed by progressive new
      matrix formation and calcified bridging. Proliferating cells peaked at 3 days
      when matrix formation was inconspicuous. Nestin-expressing cells appeared at 3
      days, were arranged beneath the newly formed matrix at 5 days, and showed
      odontoblast-like morphology by 14 days. Osteopontin immunoreactivity was detected
      just beneath the necrotic area after 1 day. These findings suggest that pulpal
      responses to MTA capping involve proliferation and migration of progenitors
      followed by their differentiation into odontoblast-like cells, a mechanism
      basically similar to those to calcium hydroxide. Osteopontin might play a
      triggering role in initiation of the pulpal reparative process.

PMID- 18634930
TI  - Lipoteichoic acid partially contributes to the inflammatory responses to
      Enterococcus faecalis.
AB  - Enterococcus faecalis, a pathogenic gram-positive bacterium, is closely related
      to refractory apical periodontitis. Because lipoteichoic acid (LTA) is considered
      a major virulence factor of gram-positive bacteria, in the present study, highly
      pure LTA from E. faecalis was prepared, and its ability to stimulate murine
      macrophages was investigated in comparison with those of the killed whole cells.
      Upon exposure to E. faecalis LTA, RAW 264.7 (a murine macrophage cell line)
      produced a significantly (p < 0.05) high level of tumor necrosis factor-alpha
      (TNF-alpha) and nitric oxide (NO) in a concentration-dependent manner. It is to
      note that the LTA was able to stimulate Toll-like receptor 2 (TLR2) but not TLR4.
      Concomitantly, LTA enhanced the DNA-binding activity of a transcription factor,
      nuclear factor-kappa B (NF-kappaB), which plays an important role in the
      transcriptional activation of genes encoding inflammatory mediators. In contrast,
      heat-killed E. faecalis stimulated both TLR2 and TLR4, whereas the killed E.
      faecalis whole cells induced significant (p < 0.05) levels of TNF-alpha and NO in
      RAW 264.7 cells as their LTA did. These results suggest that LTA partially
      contributes to E. faecalis-induced inflammatory responses.

PMID- 18634931
TI  - Hydrogen peroxide induces heme oxygenase-1 and dentin sialophosphoprotein mRNA in
      human pulp cells.
AB  - Although the induction of heme oxygenase-1 (HO-1) by hydrogen peroxide (H2O2) has
      been reported, the HO-1 and odontoblastic differentiation-inducing effects
      against H2O2 have not been clarified in human pulp cells. In this study, we
      investigated whether HO-1 is involved in the protective mechanisms against the
      cytotoxic effects of H2O2 by using a cell viability assay, and we examined the
      production of dentin sialophosphoprotein (DSPP) and other mineralization markers
      by using reverse transcriptase-polymerase chain reaction in human pulp cells.
      H2O2 decreased cell viability but increased HO-1 and DSPP expression in a
      concentration- and time-dependent manner. Antioxidants and inhibitors of HO-1,
      phosphatidylinositol-3'-kinase, extracellular signal-regulated kinase, and p38
      mitogen-activated protein kinase blocked H2O2-induced cytotoxicity and the
      expression of HO-1 and DSPP mRNA in pulp cells. These data suggest that the
      induction of HO-1 by H2O2 in pulp cells plays a protective role against the
      cytotoxic effects of H2O2 and stimulates DSPP expression, resulting in premature
      odontoblast differentiation through pathways that involve phosphatidylinositol-3'
      kinase, p38, and extracellular signal-regulated kinase.

PMID- 18634932
TI  - The properties of a new endodontic material.
AB  - The purpose of this study was to analyze the physical properties and chemical
      compositions of a new experimental cement (NEC) and compare them with mineral
      trioxide aggregate (MTA); pH, working time, setting time, dimensional changes
      following setting, flow, film thickness, and chemical composition of NEC and MTA
      were assessed. For chemical compositions, all specimens were imaged and analyzed
      by scanning electron microscopy and electron probe microanalysis (EPMA). The
      physical properties were performed according to ISO 6876:2001. Working time, pH,
      and dimensional changes of NEC and MTA showed similar results. Shorter setting
      time was obtained with the NEC compared with MTA (p < 0.05). The NEC showed more
      flow than MTA. In addition, the film thickness of the NEC was considerably less
      than the MTA (p < 0.01 and p < 0.001, respectively). EPMA investigations
      indicated that lime (CaO) was the dominant compound in NEC and MTA; however,
      other compounds were significantly different. It was concluded that the chemical
      composition of NEC is different compare with MTA; it can be concluded that the
      NEC exhibits acceptable physical properties.

PMID- 18634933
TI  - Fractographic analysis of K3 nickel-titanium rotary instruments submitted to
      different modes of mechanical loading.
AB  - The aim of the present study was to analyze the fracture surface of nickel
      titanium K3 rotary files submitted to different modes of mechanical loading.
      Torsional and flexural fatigue tests were realized separately in 2 groups of
      files. Additional 2 groups of files were tested in mixed loading modes, torsional
      test after incomplete flexural fatigue test and flexural fatigue test after
      incomplete torsional test. Scanning electronic microscopy observation was used to
      make a fractographic analysis of the files under test. The files fractured during
      torsional resistance tests showed fractographies with a central area containing
      dimples, which are oval-shaped depressions in the microstructure in places of
      high local plastic deformation. The peripheral area of these files'
      fractographies presented a flattened aspect without dimples. The fractographies
      of the files fractured by flexural fatigue presented one area with radial
      striations and another area containing dimples. The fractographic patterns
      observed when mixed loading modes were imposed correspond to the pattern defined
      by the second stage test. The patterns established for the fractured files
      provide consistent bases to explain the fracture process in clinical conditions
      by fractographic analysis.

PMID- 18634934
TI  - Evaluation of smear layer: a comparison of automated image analysis versus expert
      observers.
AB  - Consistent and reproducible evaluation techniques of the smear layer in root
      canals in scanning electron microscopy studies are needed when comparing various
      instruments and techniques. In this study, the performance of 3 experienced
      blinded evaluators applying the Hulsmann technique was compared with a digital
      analysis method. Smear layer in the apical third of root canals of 35 freshly
      extracted teeth prepared by using nickel-titanium rotary instruments, Er:YAG and
      Er,Cr:YSGG lasers was scored on coded images. There was good agreement between
      the digital analysis method and the different evaluators (kappa analysis) across
      the range of the Hulsmann scores. Image analysis might be useful for evaluating
      the degree of smear layer removal in endodontic research.

PMID- 18634935
TI  - Fatigue resistance of engine-driven rotary nickel-titanium instruments produced
      by new manufacturing methods.
AB  - The aim of the present study was to investigate whether cyclic fatigue resistance
      is increased for nickel-titanium instruments manufactured by using new processes.
      This was evaluated by comparing instruments produced by using the twisted method
      (TF; SybronEndo, Orange, CA) and those using the M-wire alloy (GTX; Dentsply
      Tulsa-Dental Specialties, Tulsa, OK) with instruments produced by a traditional
      NiTi grinding process (K3, SybronEndo). Tests were performed with a specific
      cyclic fatigue device that evaluated cycles to failure of rotary instruments
      inside curved artificial canals. Results indicated that size 06-25 TF instruments
      showed a significant increase (p < 0.05) in the mean number of cycles to failure
      when compared with size 06-25 K3 files. Size 06-20 K3 instruments showed no
      significant increase (p > 0.05) in the mean number of cycles to failure when
      compared with size 06-20 GT series X instruments. The new manufacturing process
      produced nickel-titanium rotary files (TF) significantly more resistant to
      fatigue than instruments produced with the traditional NiTi grinding process.
      Instruments produced with M-wire (GTX) were not found to be more resistant to
      fatigue than instruments produced with the traditional NiTi grinding process.

PMID- 18634936
TI  - Is adhesive cementation of endodontic posts necessary?
AB  - Recently, the appropriate, durable bond of adhesive systems and composite resin
      cements to retain endodontic posts was challenged. The question arises whether it
      would be possible to place glass fiber posts in a less technique sensitive
      conventional nonadhesive approach. The influence of nonadhesive, self-adhesive,
      and etch-and-rinse systems on load capability of postendodontic restorations was
      studied. Human maxillary central incisors were divided into 4 groups (n = 10).
      Teeth were endodontically treated and restored by using glass fiber posts luted
      with different cements/composite resin combinations: (1) RelyX Unicem (3M ESPE,
      Seefeld, Germany)/Clearfil Core (Kuraray Europe, Duesseldorf, Germany), (2) RelyX
      Unicem/LuxaCore, (3) zinc phosphate cement/Clearfil, and (4) LuxaCore (DMG,
      Hamburg, Germany)/Clearfil. A 2 mm-ferrule preparation was performed. All
      specimens received adhesively luted all-ceramic crowns and were exposed to
      thermal cycling and mechanical loading before subsequent static loading.
      Significant differences between the experimental groups regarding load capability
      and fracture patterns were observed. The conventional non-adhesive post
      cementation is less reliable to withstand simulated functional forces compared to
      adhesive approaches.

PMID- 18634937
TI  - Effect of shortened irrigation times with 17% ethylene diamine tetra-acetic acid
      on smear layer removal after rotary canal instrumentation.
AB  - The purpose of this study was to evaluate whether irrigation times of 1 minute or
      less with 1 mL of 17% ethylene diamine tetra-acetic acid (EDTA) effectively
      removed the smear layer from root canals after rotary instrumentation. Forty
      single-canal teeth were decoronated, instrumented, and divided into 3
      experimental groups (n = 10). Ten teeth served as positive and negative controls.
      The experimental groups received a final rinse with 1 mL of 17% EDTA for 1
      minute, 30 seconds, or 15 seconds followed by a final 3-mL rinse with 6% NaOCl.
      Teeth were split longitudinally and prepared for scanning electron microscopy
      imaging. Digital images (350x) of the approximate center of the coronal, middle,
      and apical sections were graded for quality of smear layer removal by 3
      endodontists. Data were analyzed with nonparametric tests, with significance
      level set at alpha = .05. Significantly greater smear layer removal was found in
      the 1-minute EDTA irrigation group than the 30-second or 15-second groups.

PMID- 18634938
TI  - The influence of cavity design and glass fiber posts on biomechanical behavior of
      endodontically treated premolars.
AB  - The aim of this study was to evaluate the effect of cavity design and glass fiber
      posts on stress distributions and fracture resistance of endodontically treated
      premolars. Fifty extracted intact mandibular premolars were divided into 5 groups
      (n = 10): ST, sound teeth (control); MOD, mesio-occlusal-distal preparation +
      endodontic treatment (ET) + composite resin restoration (CR); MODP, mesio
      occlusal-distal + ET + glass fiber post + CR; MOD2/3, mesio-occlusal-distal + two
      thirds occlusal-cervical cusp loss + ET + CR; and MODP2/3, mesio-occlusal-distal
      + two thirds cusp loss + ET + glass fiber post + CR. The specimens were loaded on
      a cusp slope until fracture. Fracture patterns were classified according to four
      failure types. Stress distributions were evaluated for each group in a two
      dimensional finite element analysis. The fracture resistance of the MODP, MOD2/3,
      and MODP2/3 groups was significantly lower than the ST and MOD groups (p < 0.05).
      The loss of dental structure and the presence of fiber post restoration reduced
      fracture resistance and created higher stress concentrations in the tooth
      restoration complex. However, when there was a large loss of dental structure
      (MODP2/3), the post reduced the incidence of catastrophic fracture types.

PMID- 18634939
TI  - Single-step apical barrier placement in immature teeth using mineral trioxide
      aggregate and management of periapical inflammatory lesion using platelet-rich
      plasma and hydroxyapatite.
AB  - We present here a case report of a tooth with an immature root with a large
      periapical lesion. The open apex was managed by placing an apical barrier using
      mineral trioxide aggregate, and the periapical lesion was treated surgically. A
      combination of platelet-rich plasma (PRP) and hydroxyapatite graft (HA) was used
      to achieve faster healing of the periapical lesion. The case was followed up for
      11 months. The indications and advantages of apical barrier placement, periapical
      surgery, and the role of PRP and HA in postsurgical healing are discussed.

PMID- 18634940
TI  - The Alaska experiment: examining its potential impact on oral surgical care.

PMID- 18634941
TI  - Third molars and the efficacy of mechanical debridement in reducing pathogen
      levels in pregnant subjects: a pilot study.
AB  - PURPOSE: To assess the impact of mechanical debridement (scaling and root
      planing), without adjunctive therapy, on reducing the numbers of periodontal
      pathogens detected in pregnant subjects with and without visible third molars.
      PATIENTS AND METHODS: Sixty-seven subjects in the second trimester of pregnancy
      were enrolled in an institutional review board-approved study. Full mouth
      periodontal exams of all teeth were conducted at baseline and postpartum.
      Presence or absence of third molars was noted. Subgingival biofilm samples were
      obtained from the mesiobuccal of all first molars at enrollment and postpartum.
      Subjects' total counts for periodontal pathogens in biofilm samples were
      determined by DNA-DNA checkerboard hybridization. We analyzed data from a
      subsample of 26 subjects. All subjects in the study were treated at enrollment by
      mechanical debridement of all teeth, including third molars. Differences between
      subjects' baseline and postpartum demographic and clinical characteristics were
      analyzed by chi(2) and t tests by presence or absence of third molars.
      Statistical significance for differences in pathogen levels was determined by
      Rank analysis of covariance. Significance was set at 0.05 without correction for
      multiple comparisons. RESULTS: Most of the 26 subjects were African American
      (61%), on Medicaid (92%), and did not smoke during pregnancy (88%). The 15
      subjects with visible third molars were significantly older (28.0 years [SD 6.4]
      vs 23.7 years [SD 3.9]). In the 11 subjects with no third molars noted, all
      pathogen counts were reduced postpartum. In the 15 subjects with visible third
      molars, total counts for each pathogen analyzed were higher postpartum as
      compared with subjects with no visible third molars, and their bacterial counts
      were increased for 5 of the 8 pathogens, including all "red cluster" pathogens.
      Differences between study groups were observed by the presence or absence of
      third molars for T. forsythia and P. nigrescens (P = .04), and for P. gingivalis,
      F. nucleatum, total "orange cluster" bacteria, and total pathogens (P < .06).
      CONCLUSION: The efficacy of mechanical debridement to lower periodontal pathogen
      counts during pregnancy was limited by the presence of visible third molars and
      should be analyzed further in larger scale trials.

PMID- 18634942
TI  - Clinical and histopathologic independent prognostic factors in oral squamous cell
      carcinoma: a retrospective study of 334 cases.
AB  - PURPOSE: This retrospective hospital-based study reviewed and evaluated the
      outcome of patients with oral squamous cell carcinoma (OSCC) with the aim of
      identifying factors affecting the clinical course and survival rate. PATIENTS AND
      METHODS: Patients with a follow-up of at least 12 months were included. The data
      collected were statistically analyzed for the presence of factors valuable for
      prognosis; survival curves were processed in accordance with the Kaplan-Meier
      method. Differences in the expression of variables in different grading levels
      were investigated. Cox's proportional hazard model for Z(i) covariates (grading,
      age, T, N) also was calculated. RESULTS: Mean patient age was 67.7 years in women
      (n = 152) and 62.4 years in men (n = 182). A total of 98 patients were identified
      with Broder's/World Health Organization grade 1 histology, 176 with grade 2, and
      55 with grade 3; 5 patients were identified as grade 4 (carcinoma in situ).
      Gender and risk factors seemed to be unrelated to prognosis, whereas a
      significant increase in mortality was seen in patients over age 70. Histological
      grading, tumor size, and neck involvement were related, as independent factors,
      in predicting survival in patients with OSCC (QM-H > 3.9). Gender, age, and risk
      factors had no statistical relationship with cancer histological differentiation.
      CONCLUSIONS: Our analysis reveals a statistically significant relationship among
      histological Broder's grading of malignancy, tumor size, locoregional
      involvement, and survival rates, underscoring the utility of tumor
      differentiation in predicting the clinical course and outcome of OSCC.

PMID- 18634943
TI  - The use of demineralized bone matrix for grafting during Le Fort I and chin
      osteotomies: techniques and complications.
AB  - PURPOSE: To examine the use of demineralized bone matrix (DBM) in maxillary and
      chin orthognathic surgery. The use of DBM in orthognathic surgery has not been
      reported in the literature. PATIENTS AND METHODS: A retrospective review of the
      orthognathic surgeries performed in 1 university was conducted. Medical records
      were assessed to determine the materials used, complications, and details of re
      operations required. RESULTS: There were 113 suitable patients identified. The
      DBM group (88 patients) consisted of 61 Le Fort I osteotomies and 46
      genioplasties; the non-DBM group (25 patients) consisted of 25 Le Fort I
      osteotomies and 4 genioplasties. The mean follow-up period was 5.9 months for the
      DBM group and 6 months for the non-DBM group. There was only 1 technique of
      applying DBM to genioplasties, but a variety of different graft material
      combinations was used in the Le Fort I osteotomies. The only significant Le Fort
      I complication was maxillary sinusitis; its incidence was 3.3% (2 out of 61) for
      the DBM group, versus 8% (2 out of 25) in the non-DBM group. All the
      genioplasties had no complications. There were 4 cases of Le Fort I osteotomies
      which were re-entered (2 cases for suspected infection and 2 cases for re
      osteotomies due to occlusal malalignment) and they showed good bony healing.
      CONCLUSION: The use of DBM does not significantly increase complications and is
      suitable to be used in both the maxilla and chin during orthognathic surgery.

PMID- 18634944
TI  - Closed versus open operative treatment of nondisplaced diacapitular (Class VI)
      fractures.
AB  - PURPOSE: The purpose of the study was assessment of whether open reduction and
      internal fixation of high nondisplaced, nondislocated diacapitular fractures
      (Class VI according to Spiessl and Schroll) have better 1-year results compared
      with closed treatment. PATIENTS AND METHODS: Twenty-two patients treated 2001 to
      2005 with 26 (4 double) Class VI fractures prospectively entered this evaluation;
      in randomized fashion 9 (41%) patients had open reduction and internal fixation,
      13 (59%) had closed treatment. Facial symmetry, nerve function, scarring, pain,
      and interincisal maximum distance were judged clinically; condylar translation by
      sonography; repositioning and reossification upon postoperative and 1-year follow
      up radiographs. RESULTS: Altogether 17 (77%) patients presented for follow-up; 8
      (47%) closed treatment, 9 (53%) open reduction and internal fixation. All
      patients evinced normal vertical opening. Insufficient condylar translation (<6
      mm opening, <3 mm protrusion and mediotrusion) was prevalent in 2 open reduction
      and internal fixation and 2 closed treatment patients, persistent pain in 2 open
      reduction and internal fixation patients, and deflection greater than 4 mm in 2
      open reduction and internal fixation patients. Partial facial nerve paresis was
      not encountered. In 1 open reduction and internal fixation patient a broken
      osteofixation was removed and 1 closed treatment patient had dysocclusion.
      Vertical medial fragment position was successfully restored by open reduction and
      internal fixation with, however, considerable remodeling (lateral condyle support
      is unaltered in Class VI). Closed treatment did not succeed in vertical
      repositioning but also evinced less remodeling. Angular fragment rectification in
      open reduction and internal fixation was successful; in closed treatment slight
      enlargement of the angulation was encountered at follow-up. CONCLUSIONS: Closed
      treatment within this study produced 2 of 8 (25%), open reduction and internal
      fixation compared with 2 of 9 (22%) unacceptable results and postoperative
      condyle remodeling. Therefore success rates of 75% versus 78% were attained, and
      closed treatment should therefore be preferred. However, sufficiently retentive
      resorbable osteofixation with intraosseous localization could permit better open
      reduction and internal fixation results than the microplates and screws at the
      dorsal condylar circumference applied within this study.

PMID- 18634945
TI  - Oral squamous cell carcinoma: a clinicopathologic review of 233 cases in Lagos,
      Nigeria.
AB  - PURPOSE: The aim of this study is to present the clinicopathologic
      characteristics of histologically diagnosed squamous cell carcinoma (SCC) of the
      oral cavity in Lagos, Nigeria, with a view toward analyzing the age, gender, site
      distribution, and histological differentiation. PATIENTS AND METHODS: All cases
      that were histologically diagnosed as SCC of the oral cavity between January 1995
      and December 2005 were retrieved from the records of the Department of Oral
      Pathology and Biology, Lagos University Teaching Hospital and the Oral Pathology
      Service, Lagos State General Hospitals. All the cases were subjected to analysis
      of age, gender, site of occurrence, symptoms at presentation, and histological
      differentiation of tumors. RESULTS: Oral SCC constituted 10.8% (n = 233) of the
      5,124 biopsy specimens obtained in all of the centers during the study period.
      The mean age (+/- standard deviation) of patients at presentation was 45.3 +/-
      19.6 years (range, 3 to 86 years), with a male:female ratio of 1.4:1; 40% of
      these patients were under age 40 years. Peak incidence was found in the 20 to 29
      year and 40 to 49-year age groups. Males were significantly younger than females
      (P = .00). Poorly differentiated SCC was the most common subtype (47.6%),
      followed by well-differentiated (32.6%) and moderately differentiated (19.7%)
      subtypes. The mandibular gingiva was the most commonly affected site (31.8%),
      followed by the maxillary gingiva (23.3%) and tongue (17.6%). The least commonly
      affected site was the floor of the mouth. CONCLUSIONS: Oral SCC is most common in
      the mandibular gingiva and in males in our environment, with 40% of cases
      occurring in patients under age 40 years. The poorly differentiated subtype is
      the most common histological differentiation.

PMID- 18634946
TI  - Correlation of radiographic size and the presence of radiopaque lamina with
      histological findings in 70 periapical lesions.
AB  - PURPOSE: This study was conducted to relate the histological diagnosis of chronic
      inflammatory periapical lesions with the radiographic images of these lesions.
      MATERIALS AND METHODS: A total of 70 biopsy specimens obtained during periapical
      surgery were stained with hematoxylin and eosin and examined under a microscope.
      Histological analysis established the diagnosis as granuloma, cyst, or scar
      tissue. The location of the lesion was recorded, as were the radiographic size
      (maximum and minimum diameter in mm and area in mm(2)) and the presence of
      radiopaque lamina around the lesion, using an image analyzing system. RESULTS:
      The distribution of the biopsy specimens was 65.7% granulomas, 25.7% scar tissue,
      and 8.6% cysts, 1 of which was a keratocyst. The largest lesions were cysts and
      epithelialized granulomas, with statistically significant differences. Radiopaque
      lamina was observed around 9 lesions; of these, only 2 were histologically
      diagnosed as cysts, with the rest as granulomas. CONCLUSIONS: Most of the apical
      lesions were granulomas. Cysts had the largest radiotransparent images; however,
      in the 70 cases studied, neither the radiographic size nor the presence of
      associated radiopaque lamina alone was sufficient to determine the type of
      lesion. Histological analysis is required.

PMID- 18634947
TI  - Relationship between histological diagnosis and evolution of 70 periapical
      lesions at 12 months, treated by periapical surgery.
AB  - PURPOSE: To relate the histologic diagnosis and radiographic size with the
      prognosis of 70 biopsies obtained via periapical surgery. MATERIALS AND METHODS:
      Seventy biopsies obtained during periapical surgery were histologically analyzed
      following curettage of the tissue, establishing the diagnosis as either apical
      granuloma, radicular cyst, or scar tissue. The radiographic size of the lesion
      (area in mm(2)) before surgery and after 1 year of follow-up was measured. The
      evolution at 12 months after surgery was evaluated according to the criteria of
      von Arx and Kurt. A statistical study was made, the inter-variable relationships
      were studied using analysis of variance with subsequent Tukey testing and
      calculation of Pearson correlation coefficient. RESULTS: Results indicated that
      65.7% of lesions were granulomas, 25.7% scar tissue, and 8.6% cysts. The larger
      lesions had the worst prognosis. Cysts had the worst evolution at 12 months after
      surgery, this result being statistically significant. CONCLUSIONS: The prognosis
      for the periapical lesion depended on the type of lesion and its radiographic
      size, with cysts and larger lesions having the worst evolution.

PMID- 18634948
TI  - Stability of soft tissue profile after mandibular setback in sagittal split
      osteotomies: a longitudinal and long-term follow-up study.
AB  - PURPOSE: The aim of the study was to conduct a long-term prospective follow-up on
      the stability of soft tissues after bilateral sagittal split osteotomy (BSSO)
      with rigid internal fixation to set back the mandible. PATIENTS AND METHODS:
      Seventeen consecutive patients (6 females, 11 males) were re-examined 12.7 years
      (T5) after surgery. The precedent follow-ups included: before surgery (T1), 5
      days (T2) after surgery, 6.6 months (T3) after surgery, and 14.4 months after
      (T4) surgery. Lateral cephalograms were traced by hand, digitized, and evaluated
      with the Dentofacial Planner program (Dentofacial Software, Toronto, Canada). The
      x-axis for the system of coordinates ran through Sella (point 0) and the line NSL
      -7 degrees. RESULTS: The net effect of the soft tissue chin (soft tissue
      pogonion) was 79% of the setback at pogonion. At the lower lip (labrale inferior)
      it was 100% of the setback at lower incisor position. Point B' followed point B
      to 99%. Labrale inferior and menton' also showed a significant backward, as well
      as a downward, movement (T5 to T2). Gender correlated significantly (P = .004)
      with the anterior displacement of point B' and pogonion' (P = .012). The soft
      tissue relapse 12.7 years after BSSO setback surgery at point B' was 3% and 13%
      at pogonion'. CONCLUSION: Among the reasons for 3-dimensional long-term soft
      tissue changes of shape, the surgical technique, the normal process of human
      aging, the initial growth direction, and remodeling processes must be considered.
      Growth direction positively influenced the long-term outcome of setback surgery
      in female compared with male patients because further posterior movement of the
      mandibular soft tissue occurred.

PMID- 18634949
TI  - Radiographic study of the positional changes and eruption of impacted third
      molars in young adults of an Asian Indian population.
AB  - PURPOSE: The aim of the study was to assess changes in the angular position and
      eruption status of third molars in students of an Asian Indian population during
      a 4-year follow-up period. PATIENTS AND METHODS: The series consisted of 43
      students (11 males, 32 females). Standardized panoramic radiographs were taken at
      baseline (mean age, 19.1 +/- 0.7 years) and at the end of study (mean age 23.1 +/
      0.7 years). Angulation and degree of impaction of third molars were determined
      by their sagittal relationship to the adjacent second molar and eruption to the
      occlusal plane. Root formation was also assessed. RESULTS: During the 4-year
      follow-up period, 11 of 72 of the mandibular teeth (15%) and 17 of 74 of the
      maxillary teeth (23%) changed their sagittal inclination. Thirty-one of 118
      impacted teeth (26%; level B + C) achieved level A eruption more so in the
      mandible, ie, 15 of 52 (29%), than in the maxilla, ie, 16 of 66 (24%). In the
      mandible, 9 of 24 impacted vertical teeth (37.5%), 3 of 6 distoangular teeth
      (50%), and 3 of 22 mesioangular impacted teeth (13.6%) erupted to the occlusal
      plane. In the maxilla, 9 of 36 impacted vertical teeth (25%) and 7 of 27
      distoangular teeth (26%) erupted to the occlusal plane during the follow-up. The
      number of teeth with complete root formation increased in mandible from 61% to
      93% and in maxilla from 62% to 94.5%. CONCLUSIONS: Unpredictable changes in the
      position and angulation of teeth continued to occur even after the age of 19
      years, more so in vertical and distoangular teeth than in mesioangular teeth.

PMID- 18634950
TI  - Predictability of prebent advancement plates for use in maxillomandibular
      advancement surgery.
AB  - PURPOSE: The purpose of this study was to determine the predictability when using
      prebent advancement (PBA) plates in the maxillary osteotomies of
      maxillomandibular advancement (MMA) surgery. MATERIALS AND METHODS: A
      retrospective review of the MMA surgeries at University of Alabama at Birmingham
      was carried out. Thirty-six obstructive sleep apnea patients who underwent MMA
      with PBA were included in this study. All cases had fixation of the maxillary
      osteotomies with KLS Martin PBA titanium plates and screws (KLS Martin,
      Jacksonville, FL). Lateral cephalometric radiographs were taken within 1 month
      before surgery (T1), and between 2 to 4 weeks postsurgically (T2). All
      cephalometric radiographs were analyzed using Planmeca Dimaxis Imaging Software
      (Helsinki, Finland). Vertical and horizontal measurements were made to several
      skeletal landmarks including Sella (S), A point (APT), and upper incisor (UPI).
      The amount of advancement was measured through pre- and postoperative lateral
      cephalographs and compared with the magnitude of the advancement plates used.
      RESULTS: All data of 36 patients were included and used for statistics. The data
      showed that the mean difference was 0.74 mm (advancement is more than the size of
      the PBA plates) and the mean percentage difference was 11.35%. Fifty percent of
      the cases had the magnitude of advancement within 1 mm of the PBA size. The
      predictive analysis found that the PBA size was a significant predictor for the
      advancement achieved (P < .0001) but not the absolute difference between the
      advancement achieved and the plate size (P = .0726) and the relative advancement
      difference (P = .0612). The absolute difference and the relative difference take
      into account the size of the PBA and are better parameters to judge the
      predictability of the advancement achieved. The rationale for this
      unpredictability is largely due to the anatomy of the maxilla and pyriform rims
      and the adaptation of the PBA to the maxilla. CONCLUSION: There are distinct
      advantages to the use of PBA plates. The PBA plates have been proven to
      significantly affect the advancement. However, when very precise movements are
      required, the size of the PBA used does not predictably correlate to and
      frequently underestimates the amount of advancement achieved. Therefore accurate
      model surgeries are still required for most cases.

PMID- 18634951
TI  - Incidence and severity of maxillofacial injuries during the Second Lebanon War
      among Israeli soldiers and civilians.
AB  - PURPOSE: To analyze the incidence and severity of maxillofacial injuries in the
      Second Lebanon War, that occurred during the summer of 2006, among Israeli
      soldiers and civilians. PATIENTS AND METHODS: This is a retrospective cohort
      study of patients recorded in the Israel National Trauma Registry during the
      Second Lebanon War. Data refer to all general hospitals throughout the country.
      Data were analyzed according to the etiology of the injury, severity of trauma
      using the Injury Severity Score, trauma location, and duration of hospital stay.
      Cases with multiple injuries that included maxillofacial injuries were separated
      and further analyzed according to the above parameters. Patients with only dental
      injuries and superficial facial soft tissue lacerations were excluded because
      they were referred to the military dental clinics and not to general hospitals.
      RESULTS: Maxillofacial injuries were found in 36 (6.4%) of the 565 wounded.
      Patients with maxillofacial injuries ranged in age from 20 to 44 years (mean age,
      25.5 +/- 5.7 years). Greater than 50% of the injuries required more than 3
      hospitalization days. Mortality rate of the maxillofacial injured was 2.8%. Most
      of the maxillofacial injuries (33; 91.7%) were combined with other organ
      injuries; 9 (25%) patients also had dental injuries. CONCLUSION: In the Second
      Lebanon War, the incidence and severity of true maxillofacial injuries, without
      dental injuries alone, were relatively low compared with previous reports of
      other conflicts. However, because most injuries involved multiple organs, special
      attention is required when planning and providing emergency, as well as secondary
      and tertiary medical care to war wounded.

PMID- 18634952
TI  - Stability after bilateral sagittal split osteotomy setback surgery with rigid
      internal fixation: a systematic review.
AB  - PURPOSE: The purpose of this systematic review was to evaluate relapse and its
      causes in bilateral sagittal split setback osteotomy with rigid internal
      fixation. MATERIALS AND METHODS: Literature research was done in databases such
      as PubMed, Ovid, the Cochrane Library, and Google Scholar Beta. From the original
      488 articles identified, 14 articles were finally included. Only 5 studies were
      prospective and 9 retrospective. The range of postoperative study records was
      from 6 weeks to 12.7 years. RESULTS: The horizontal short-term relapse was
      between 9.9% and 62.1% at point B and between 15.7% and 91.3% at pogonion. Long
      term relapse was between 14.9% and 28.0% at point B and between 11.5% and 25.4%
      at pogonion. CONCLUSIONS: Neither large increase nor decrease of relapse was seen
      when short-term values were compared with long-term. Bilateral sagittal split
      osteotomy for mandibular setback in combination with orthodontics is an effective
      treatment of skeletal Class III and a stable procedure in the short- and long
      term. The etiology of relapse is multifactorial: the proper seating of the
      condyles, the amount of setback, the soft tissue and muscles, remaining growth
      and remodeling, and gender were identified. Age did not show any correlations. To
      obtain reliable scientific evidence, further short- and long-term research of
      bilateral sagittal split osteotomy setback with rigid internal fixation should
      exclude additional surgery, ie, genioplasty or maxillary surgery, and include
      correlation statistics.

PMID- 18634953
TI  - Effect of botulinum toxin-A in myofascial pain patients with or without
      functional disc displacement.
AB  - PURPOSE: To evaluate the effects of botulinum toxin-A in the treatment of
      patients who have myofascial pain with or without functional disc displacement.
      PATIENTS AND METHODS: Twenty-four participants were randomly assigned to the
      study by using Research Diagnostic Criteria for Temporomandibular Disorders. All
      patients were informed about botulinum toxin-A, and were required to give
      informed consent. Before the injections, patients were asked to fill out a
      Biobehavioral Questionnaire to evaluate their pain and psychological status, and
      afterward, electromyography of the right and left masseter and anterior temporal
      muscles was recorded. Saline was injected into the masseter and anterior temporal
      muscles in the placebo group, and botulinum toxin-A was used in the study group.
      On days 14 and 28, patients were asked to fill out a Biobehavioral Questionnaire
      again, and electromyography of the right and left masseter and anterior temporal
      muscles was recorded again. RESULTS: The study group showed improvement in pain
      and psychological status. Although a decrease in the action potentials of the
      masseter muscles on day 14 was followed by an increase on day 28, the reduction
      of pain scores and improvement in psychological status continued on day 28.
      CONCLUSIONS: The injection of botulinum toxin-A decreases the muscle action
      potential in 14 days. The patients also show improvement in pain and
      psychological status.

PMID- 18634954
TI  - Prevalence and prediction of difficult intubation in maxillofacial surgery
      patients.
AB  - PURPOSE: The failure to maintain a patent airway after the induction of general
      anesthesia is a major concern for anesthesiologists. For securing the airway,
      tracheal intubation using direct laryngoscopy remains the method of choice in
      most cases. However, direct laryngoscopic intubation is difficult in 1% to 4%,
      and impossible in 0.05% to 0.35%, of patients who have seemingly normal airways.
      This study sought to determine the prevalence of difficult intubation in
      maxillofacial surgery patients, and to evaluate the usefulness of various
      predictive tests for difficult intubation. PATIENTS AND METHODS: This study was
      conducted on 208 patients undergoing maxillofacial surgery. During the
      preoperative visit, patients were examined in terms of the test of Mallampati et
      al (Can Anaesth Soc J 32:429, 1985), thyromental distance, sternomental distance,
      and interincisal distance. Direct laryngoscopic grading, as defined by Cormack
      and Lehane (Anesthesia 39:1105, 1984), was recorded for each patient. An
      intubation of "no difficulty" was noted when the tube was inserted into the fully
      visualized larynx with little effort on the first attempt. RESULTS: Intubation
      was possible in all patients. Combinations of different predictive tests resulted
      in higher sensitivity. Among all test types, that of Cormack and Lahene was
      thought to exhibit the highest sensitivity and positive predictive values when
      used alone. The prevalence of difficult intubation in our group of maxillofacial
      surgery patients was 15.4%. It may be concluded that a combination of predictive
      variables can be used to improve sensitivity. CONCLUSIONS: We demonstrated that
      combining the Mallampati test with other instruments of measurement resulted in
      higher sensitivity than when either test was used alone.

PMID- 18634955
TI  - Large ulceration of the palate.

PMID- 18634956
TI  - Neuro-reflexotherapy for the management of myofascial temporomandibular joint
      pain: a double-blind, placebo-controlled, randomized clinical trial.
AB  - PURPOSE: To assess the efficacy of neuro-reflexotherapy intervention (NRT) for
      treating temporomandibular joint dysfunction attributed to myofascial pain. Neuro
      reflexotherapy intervention consists of the temporary implantation of epidermal
      devices in trigger points in the back and ear. It has shown efficacy,
      effectiveness, and cost-effectiveness in treating subacute and chronic common
      back pain. No study, however, has explored its efficacy in treating myofascial
      temporomandibular joint pain (MF/TMJP). PATIENTS AND METHODS: This was a
      randomized, double-blind, placebo-controlled trial. Patients with MF/TMJP for
      more than 3 months in spite of conservative treatment, and with no evidence of
      major structural damage in the joint, were recruited at the Maxillofacial
      Department of the Hospital Clinico Universitario, a teaching hospital in Madrid,
      Spain. Patients were randomly assigned to an intervention group and to a control
      group. Patients in the treated group underwent 2 NRTs, immediately after baseline
      assessment and 45 days later. Sham interventions in the control group consisted
      of placement of the same number of epidermal devices within a 5-cm radius of the
      target zones. In both groups, conservative treatment during follow-up was allowed
      and recorded. Patients underwent clinical evaluations on 4 occasions: 5 minutes
      before intervention, 5 minutes after intervention, and 45 and 90 days later. The
      preintervention assessment was performed by the physician at the hospital service
      who included the patient in the study. The 3 follow-up assessments were performed
      independently by 1 of 2 physicians who had no connection with the research team,
      and who were blinded to patients' assignments. The primary outcome variable was
      level of pain severity during jaw movements at the last assessment (90 days), and
      the key comparison of interest was change in pain over time (pain levels at
      baseline and at 90 days). Level of pain was measured using a visual analog scale
      (VAS). RESULTS: Fifty-one patients with MF/TMJP were recruited into the study.
      Random assignment allocated 27 patients to the intervention group, and 24 to the
      control group. Differences in pain severity in favor of the intervention group
      appeared immediately after the intervention, persisted for 45 days, and increased
      after the second intervention. Differences at last follow-up were highly
      clinically and statistically significant (4 to 5 points on the VAS, P = .000),
      allowing for patients in the intervention group to cease drug treatment (P =
      .005). There were no differences in the evolution of crepitus or clicking in the
      joint. There were no clinically relevant side effects associated with the
      intervention. CONCLUSIONS: For patients in whom conservative treatment has
      failed, NRT improves the chronic pain associated with MF/TMJP syndrome.

PMID- 18634958
TI  - Rejuvenation of the periorbital complex with autologous fat transfer: current
      therapy.
AB  - PURPOSE: This article examines the pathophysiology of periorbital aging and
      details a technique, autologous fat transfer, to restore a youthful appearance to
      the periorbital complex. The use of photographs taken of patients in their late
      teens or early 20s shows that the main changes of periorbital aging are
      consistent with volume loss more so than gravitational changes. This article
      reflects on the shortcomings of currently accepted surgical approaches to the
      rejuvenation of the periorbital region. PATIENTS AND METHODS: After a detailed
      clinical evaluation of the periorbital region including overall facial aging,
      brow position, and eyelid laxity, patients underwent autologous fat transfer to
      the periorbital region. The technique consists of autologous fat harvesting using
      the senior author's modification of the Coleman technique to the upper brow and
      lower eyelid region. RESULTS: Detailed clinical evaluations of each subject, and
      comparisons to a preoperative youthful photograph of each, were made at 1 week, 6
      weeks, and 6 months postoperatively. These evaluations included subjective
      clinical estimations of overall brow fullness, brow position, and upper and lower
      eyelid laxity; a judgment of the appearance of the supraorbital and infraorbital
      rim; appearance of a short lower eyelid length, and an assessment of the
      subject's convex facial profile. While maintaining a natural, "nonsurgical"
      appearance with this approach and this technique, the patient achieved a more
      youthful look after autologous fat transfer. CONCLUSIONS: Although there are
      still indications for brow lift and blepharoplasty in certain patients, neither
      procedure restores a youthful, rejuvenated appearance to the periorbital complex
      as well as autologous fat transfer.

PMID- 18634957
TI  - The use of 3-dimensional reconstructions to evaluate the anatomic relationship of
      the mandibular canal and impacted mandibular third molars.

PMID- 18634959
TI  - Indications of arthroscopy in the treatment of synovial chondromatosis of the
      temporomandibular joint: report of 5 new cases.

PMID- 18634960
TI  - Long-term microscopic and tissue analytical findings for 2 frontal sinus
      obliteration materials.

PMID- 18634961
TI  - Salivary duct carcinoma of the parotid gland: case report and review of the
      literature.

PMID- 18634962
TI  - Li-Fraumeni syndrome: a case with 4 separate primary sarcomas and 5 sequential
      free flaps in the maxillofacial region.

PMID- 18634963
TI  - Lemierre syndrome and descending necrotizing mediastinitis following dental
      extraction.

PMID- 18634964
TI  - Recurrent noma (cancrum oris) in human immunodeficiency virus infection and
      acquired immunodeficiency syndrome (HIV and AIDS): report of a case.

PMID- 18634965
TI  - Solitary hydatid cyst in the mandible: case report and review of the literature.

PMID- 18634966
TI  - Treatment of painful and recurrent oral mucoceles with a high-potency topical
      corticosteroid: a case report.

PMID- 18634967
TI  - Swordfish bill injury involving the pterygomaxillary fossae: surgical management
      and case report.

PMID- 18634968
TI  - Plunging ranula following placement of mandibular implants: case report.

PMID- 18634969
TI  - Atraumatic percutaneous transfer of an externally ported distractor activation
      arm.

PMID- 18634971
TI  - Fully automated registration of intraoperative computed tomography image data for
      image-guided craniofacial surgery.

PMID- 18634970
TI  - Ultrasonographic assessment of new bone formation in maxillary distraction
      osteogenesis.

PMID- 18634972
TI  - Usefulness of 18F-fluorodeoxyglucose positron emission tomography for detecting
      ameloblastoma, with special reference to glucose transporter-1 expression.

PMID- 18634973
TI  - Optimizing craniofacial osteotomies: applications of haptic and rapid prototyping
      technology.

PMID- 18634974
TI  - Use of the endoscope in bisagittal split osteotomy.

PMID- 18634975
TI  - A crisis perspective in balance.

PMID- 18634976
TI  - Collective dynamics: topics on competition and cooperation in the biosciences.
      Foreword.

PMID- 18634977
TI  - Molecular genetics of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. There
      is genetic predisposition for the development of AF. Recently, by linkage
      analysis, several loci have been mapped for monogenetic AF, including 11p15.5,
      21q22, 17q, 7q35-36, 5p13, 6q14-16, and 10q22. Some of these loci encode for
      subunits of potassium channels (KCNQ1, KCNE2, KCNJ2, and KCNH2 genes), and the
      remaining are yet unidentified. All of the known mutations are associated with a
      gain of function of repolarization potassium currents, resulting in a shortening
      of action potential duration and atrial refractory period, which facilitate
      multiple re-entrant circuits in AF. In addition to familial AF, common AF often
      occurs in association with acquired diseases such as hypertension, valvular heart
      disease, and heart failure. By genetic association study, some genetic variants
      or polymorphisms related to the mechanism of AF have been found to be associated
      with common AF, including genes encoding for subunits of potassium or sodium
      channels, sarcolipin gene, renin-angiotensin system gene, connexin-40 gene,
      endothelial nitric oxide synthase gene, and interleukin-10 gene. These
      observations suggest that genes related to ionic channels, calcium handling
      protein, fibrosis, conduction and inflammation play important roles in the
      pathogenesis of common AF. The complete elucidation of genetic loci for common AF
      is still in its infancy. However, the availability of genomewide scans with
      hundreds or thousands of polymorphisms has made it possible. However, challenges
      and pitfalls exist in association studies, and consideration of particular
      features of study design is necessary before making definite conclusions from
      these studies.

PMID- 18634978
TI  - Nitrate-induced toxicity and preconditioning: a rationale for reconsidering the
      use of these drugs.
AB  - Although organic nitrates have been clinically used for more than a century,
      findings in the last decade have radically challenged our traditional view
      concerning the mechanism(s) of their clinical effects and implications. While
      their hemodynamic properties are well known, the knowledge that nitrates possess
      previously unexpected nonhemodynamic effects is a unique opportunity of which
      clinicians should be aware but, at the same time, it also provides a rationale to
      worry about previously unanticipated clinical consequences of long-term treatment
      with these drugs.

PMID- 18634979
TI  - Effect of diabetes on progression of coronary atherosclerosis and arterial
      remodeling: a pooled analysis of 5 intravascular ultrasound trials.
AB  - OBJECTIVES: Our goal was to characterize coronary atherosclerosis progression and
      arterial remodeling in diabetic patients. BACKGROUND: The mechanisms that
      underlie adverse cardiovascular outcomes in diabetic patients have not been well
      characterized. METHODS: A systematic analysis was performed in 2,237 subjects in
      randomized controlled studies of atherosclerosis progression. The pattern of
      arterial remodeling, extent of coronary atherosclerosis, and disease progression
      was compared in subjects with and without diabetes. RESULTS: In association with
      more risk factors, diabetic patients demonstrated a greater percent atheroma
      volume (PAV) (40.2 +/- 0.9% vs. 37.5 +/- 0.8%, p < 0.0001) and total atheroma
      volume (TAV) (199.4 +/- 7.9 mm(3) vs. 189.4 +/- 7.1 mm(3), p = 0.03) on
      multivariate analysis. A stronger correlation was observed between PAV and
      glycated hemoglobin (r = 0.22, p = 0.0003) than fasting glucose (r = 0.09, p <
      0.0001), although the difference just failed to meet statistical significance
      after controlling for study. Diabetic patients exhibited a smaller lumen (291.1
      +/- 104.8 mm(3) vs. 306.5 +/- 108.2 mm(3), p = 0.005) but no difference in
      external elastic membrane (494.9 +/- 166.9 mm(3) vs. 498.8 +/- 167.2 mm(3), p =
      0.61) volumes. More rapid progression of PAV (0.6 +/- 0.4% vs. 0.05 +/- 0.3%, p =
      0.0001) and TAV (-0.6 +/- 2.5 mm(3) vs. -2.7 +/- 2.4 mm(3), p = 0.03) was
      observed in diabetic patients on multivariate analysis. Smaller external elastic
      membrane (482.5 +/- 160.7 mm(3) vs. 519.9 +/- 166.9 mm(3), p = 0.03) and lumen
      (276.0 +/- 100.3 mm(3) vs. 310.1 +/- 105.6 mm(3), p = 0.001) volumes were
      observed in diabetic patients treated with insulin despite the presence of a
      similar TAV (206.5 +/- 88.6 mm(3) vs. 209.9 +/- 90.2 mm(3), p = 0.84). Intensive
      low-density lipoprotein cholesterol lowering in patients improved the rate of
      plaque progression, but only to the level observed in nondiabetic patients with
      suboptimal lipid control. CONCLUSIONS: Diabetes is accompanied by more extensive
      atherosclerosis and inadequate compensatory remodeling. Accelerated plaque
      progression, despite use of medical therapies, supports the need to develop new
      antiatherosclerotic strategies in diabetic patients.

PMID- 18634980
TI  - Diabetic coronary artery disease: how little we know and how little intravascular
      ultrasound has taught us.

PMID- 18634981
TI  - Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type
      natriuretic peptide in patients with chronic heart failure: prediction of death
      at different stages of the disease.
AB  - OBJECTIVES: This study sought to evaluate the predictive value of copeptin over
      the entire spectrum of heart failure (HF) and compare it to the current benchmark
      markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic
      peptide (NT-proBNP). BACKGROUND: Vasopressin has been shown to increase with the
      severity of chronic HF. Copeptin is a fragment of pre-pro-vasopressin that is
      synthesized and secreted in equimolar amounts to vasopressin. Both hormones have
      a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin,
      copeptin is very stable in vitro. The predictive value of copeptin has been shown
      in advanced HF, where it was superior to BNP for predicting 24-month mortality.
      METHODS: This was a long-term observational study in 786 HF patients from the
      whole spectrum of heart failure (New York Heart Association [NYHA] functional
      class I to IV, BNP 688 +/- 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular
      ejection fraction 25 +/- 10% [range 5% to 65%]). RESULTS: The NYHA functional
      class was the most potent single predictor of 24-month outcome in a stepwise Cox
      regression model. The BNP, copeptin, and glomerular filtration rate were related
      to NYHA functional class (p < 0.0001 for trend). Copeptin was the most potent
      single predictor of mortality in patients with NYHA functional class II (p <
      0.0001) and class III (p < 0.0001). In NYHA functional class IV, the outcome of
      patients was best predicted by serum sodium, but again, copeptin added additional
      independent information. CONCLUSIONS: Increased levels of copeptin are linked to
      excess mortality, and this link is maintained irrespective of the clinical signs
      of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this
      study, but the markers seem to be closely related.

PMID- 18634982
TI  - Circumferential pulmonary vein isolation with the cryoballoon technique results
      from a prospective 3-center study.
AB  - OBJECTIVES: The purpose of this study was to investigate the efficacy safety of
      the novel cryoballoon device (Arctic Front, Cryocath, Quebec, Canada).
      BACKGROUND: Antral pulmonary vein (PV) ablation with radiofrequency energy is
      widely used as a strategy for catheter ablation of paroxysmal atrial fibrillation
      (PAF). A novel double lumen cryoballoon catheter was designed for circumferential
      pulmonary vein isolation (PVI) with the cryoablation technique. METHODS: We
      consecutively enrolled 346 patients with symptomatic, drug refractory paroxysmal
      (n = 293) or persistent (n = 53) atrial fibrillation (AF). In all patients, PVI
      of all targeted PVs was the therapeutic aim. The primary end points of this
      nonrandomized study were: 1) acute isolation rate of targeted PV; and 2) first
      electrocardiogram-documented recurrence of AF. The secondary end point was
      occurrence of PV stenosis or atrio-esophageal fistula. RESULTS: The 1,360 of
      1,403 PVs (97%) were targeted with balloons or balloons in combination with the
      use of Freezor Max (Cryocath). We found that ablation with the cryoballoon
      resulted in maintenance of sinus rhythm in 74% of patients with PAF and 42% of
      patients with persistent AF. No PV narrowing occurred. The most frequent
      complication was right phrenic nerve palsy observed during cryoballoon ablation
      at the right superior PV. CONCLUSIONS: Pulmonary vein isolation with a new
      cryoballoon technique is feasible. Sinus rhythm can be maintained in the majority
      of patients with PAF by circumferential PVI using a cryoballoon ablation system.
      Cryoablation was less effective in patients with persistent AF than in patients
      with PAF.

PMID- 18634983
TI  - Prediction of cardiac events in patients with reduced left ventricular ejection
      fraction with dobutamine cardiovascular magnetic resonance assessment of wall
      motion score index.
AB  - OBJECTIVES: The purpose of this study was to assess the utility of dobutamine
      cardiovascular magnetic resonance (DCMR) results for predicting cardiac events in
      individuals with reduced left ventricular ejection fraction (LVEF). BACKGROUND:
      It is unknown whether DCMR results identify a poor cardiac prognosis when the
      resting LVEF is moderately to severely reduced. METHODS: Two hundred consecutive
      patients ages 30 to 88 (average 64) years with an LVEF <or=55% that were poorly
      suited for stress echocardiography underwent DCMR in which left ventricular wall
      motion score index (WMSI), defined as the average wall motion of the number of
      segments scored, was assessed at rest, during low-dose, and after peak
      intravenous infusion of dobutamine/atropine. All participants were followed for
      an average of 5 years after DCMR to ascertain the post-testing occurrence of
      cardiac death, myocardial infarction (MI), and unstable angina or congestive
      heart failure warranting hospital stay. RESULTS: After accounting for risk
      factors associated with coronary arteriosclerosis and MI, a stress-induced
      increase in WMSI during DCMR was associated with future cardiac events (p <
      0.001). A DCMR stress-induced change in WMSI added significantly to predicting
      future cardiac events (p = 0.003), after accounting for resting LVEF, but this
      predictive value was confined primarily to those with an LVEF >40%. CONCLUSIONS:
      In individuals with mild to moderate reductions in LVEF (40% to 55%), dobutamine
      induced increases in WMSI forecast MI and cardiac death to a greater extent than
      an assessment of resting LVEF. In those with an LVEF <40%, a dobutamine-induced
      increase in WMSI does not predict MI and cardiac death beyond the assessment of
      resting LVEF.

PMID- 18634984
TI  - Exaggerated blood pressure response to exercise is associated with augmented rise
      of angiotensin II during exercise.
AB  - OBJECTIVES: The aim of this study was to investigate the association between an
      exaggerated blood pressure (BP) response to exercise and augmented angiotensin
      (Ang) II rise during exercise. BACKGROUND: Although a central pressor effect of
      Ang II has been implicated in the pathogenesis of hypertension, the relationship
      between Ang II and exaggerated BP response to exercise is unclear. METHODS:
      Thirty-six subjects with an exaggerated BP response to exercise (18 men, age 50
      +/- 16 years, Group II) were compared with 36 age- and gender-matched control
      subjects (18 men, age 50 +/- 16 years, Group I) with normal BP reactivity. The
      subjects who had resting BP >or=140/90 mm Hg or were treated with any
      antihypertensive drugs were excluded. The blood was sampled at rest and
      immediately after peak exercise for measurement of renin, Ang II, aldosterone,
      and catecholamine. RESULTS: At rest, there were no significant differences in BP,
      renin, aldosterone, and catecholamine levels between the 2 groups. The renin,
      aldosterone, and catecholamine were increased during exercise, but there were no
      significant differences between the groups. However, log Ang II at rest (0.78 +/-
      0.32 vs. 0.98 +/- 0.38, p = 0.004) and peak exercise (0.84 +/- 0.35 vs. 1.17 +/-
      0.51, p < 0.001) and the magnitude of the increment of log Ang II with exercise
      (0.06 +/- 0.12 vs. 0.19 +/- 0.20, p = 0.003) were significantly higher in the
      exaggerated BP response group. CONCLUSIONS: An exaggerated BP response to
      exercise was associated with augmented rise of Ang II during exercise.

PMID- 18634985
TI  - Childhood levels of serum apolipoproteins B and A-I predict carotid intima-media
      thickness and brachial endothelial function in adulthood: the cardiovascular risk
      in young Finns study.
AB  - OBJECTIVES: The aim of this study was to determine whether apolipoproteins (apo)
      B and A-I measured in childhood and adolescence predict atherosclerosis in
      adulthood. BACKGROUND: Exposure to dyslipidemia in childhood predicts the
      development of atherosclerosis. Apolipoproteins B and A-I might be good markers
      of atherogenic dyslipidemia, but there is a paucity of information concerning
      their importance in childhood. METHODS: Apolipoproteins B and A-I, low-density
      lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol,
      triglycerides, blood pressure, obesity, insulin, C-reactive protein, and smoking
      were assessed in 1980 and 2001 among 879 subjects in the Cardiovascular Risk in
      Young Finns Study (ages 3 to 18 years at baseline). Carotid artery intima-media
      thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured in
      2001 at the age of 24 to 39 years. RESULTS: In subjects ages 12 to 18 years at
      baseline, apoB and apoB/apoA-I ratio were directly (p < 0.001) related and apoA-I
      was inversely (p = 0.01) related with adulthood IMT. In subjects ages 3 to 18
      years at baseline, apoB (p = 0.02) and the apoB/apoA-I ratio (p < 0.001) were
      inversely related and apoA-I (p = 0.003) was directly related to adulthood FMD.
      These relations were not altered when the effects of nonlipid risk factors and
      adulthood apolipoproteins were taken into account. The apoB/apoA-I ratio measured
      in adolescence was superior to LDL/HDL ratio (c-values, 0.623 vs. 0.569, p =
      0.03) in predicting increased IMT in adulthood (IMT >or=90th percentile and/or
      carotid plaque). CONCLUSIONS: Apolipoproteins B and A-I measured in children and
      adolescents reflect a lipoprotein profile predisposing to the development of
      subclinical atherosclerosis in adulthood. These markers might have value in
      pediatric lipid risk assessment.

PMID- 18634986
TI  - We must prevent disease, not predict events.

PMID- 18634987
TI  - Blockade of angio-associated migratory cell protein inhibits smooth muscle cell
      migration and neointima formation in accelerated atherosclerosis.
AB  - OBJECTIVES: The aim of this study was to elucidate the role of angio-associated
      migratory cell protein (AAMP) for the migration of vascular smooth muscle cells
      (SMCs) and for the development of neointimal hyperplasia after vascular injury.
      BACKGROUND: Although AAMP has been shown to participate in angiogenesis and
      cancerogenesis and is predominantly expressed in cells with a migratory
      phenotype, involvement of AAMP during neointima (NI) formation after arterial
      injury has not been analyzed previously. METHODS: The AAMP content in SMCs was
      examined using 2-photon laser-scanning microscopy and subcellular fractioning.
      Migratory potential of SMCs transiently transfected with AAMP expression vectors,
      transfected with small interfering ribonucleic acid (siRNA), or treated with
      antirecombinant angio-associated migratory cell protein-antibody (anti-rAAMP-ab)
      was examined using transwell migration chamber assays. Expression of AAMP was
      determined in the atherogenic apolipoprotein E knockout (apoE(-/-)) mouse model
      and in the porcine coronary restenosis model by immunohistochemistry and by
      Western blot. ApoE(-/-) mice were treated intraperitoneally with anti-rAAMP-ab,
      and wire-injured carotid arteries were examined. RESULTS: Angio-associated
      migratory cell protein is localized in the membrane of SMCs, and its expression
      is enhanced in NI-derived SMCs. The AAMP overexpression increases, while both
      treatment with anti-rAAMP-ab and transfection with siRNA decreases SMC migration.
      Knockdown of AAMP decreases RhoA activity in the membrane fraction of SMCs. The
      AAMP expression by SMCs is enhanced in both animal models. Anti-rAAMP-ab reduces
      neointimal SMC density at 1 week and NI formation at 4 weeks in apoE(-/-) mice
      without affecting proliferation of SMCs. CONCLUSIONS: These data reveal an
      important functional role of AAMP in the migration of SMCs, identifying AAMP as a
      potential target to limit lesion formation after injury.

PMID- 18634988
TI  - Angio-associated migratory cell protein and smooth muscle cell migration in
      development of restenosis and atherosclerosis.

PMID- 18634989
TI  - Long-term outcome among patients with ST-segment elevation myocardial infarction
      complicated by shock.

PMID- 18634990
TI  - Driving and ventricular arrhythmia: a historical perspective.

PMID- 18634993
TI  - The timing of thrombolysis for strokes complicating cardiac catheterization.

PMID- 18634996
TI  - Improving outcomes for severe sepsis and septic shock: tools for early
      identification of at-risk patients and treatment protocol implementation.
AB  - Sepsis is a significant problem, and septicemia is the 10th leading cause of
      death in the United States. Sepsis incidence is increasing, and the mortality
      rate is 20% to 50% for patients with severe sepsis. This article identifies
      methods for improving outcomes of severe sepsis and septic shock. Included are
      recommendations for diagnosis and treatment. Case studies are included.

PMID- 18634998
TI  - At the flick of a switch: epigenetic drugs.

PMID- 18635000
TI  - Bivalent aptamers deliver the punch.
AB  - Aptamers, sometimes termed "chemical antibodies," have been engineered into
      multimerized versions for therapeutic application. The groups of Gilboa and
      Sullenger now report the development of a bivalent aptamer-molecular device as a
      receptor agonist that has the same functional properties, but stronger avidity
      than a corresponding antibody.

PMID- 18634999
TI  - A glycan shield for bacterial sphingolipids.
AB  - In this issue of Chemistry & Biology, Kinjo et al. (2008) propose that the
      addition of oligosaccharides to the core outer membrane glycosphingolipid in
      Sphingomonas spp. may be an adaptation that allows bacteria to evade recognition
      by Natural Killer T cells, thus suggesting a remarkable process of host/pathogen
      coevolution.

PMID- 18635001
TI  - The small-molecule iron transport inhibitor ferristatin/NSC306711 promotes
      degradation of the transferrin receptor.
AB  - Iron delivery by transferrin (Tf) is accomplished through clathrin-mediated
      endocytosis of Tf receptors. The small molecule NSC306711 inhibits iron uptake
      from the Tf-TfR pathway. Here we show that the drug's mechanism of action is to
      induce internalization and degradation of unoccupied Tf receptors through an
      unexpected endocytic pathway. Unlike classical clathrin-mediated Tf receptor
      endocytosis, internalization promoted by NSC306711 is independent of clathrin and
      dynamin, and is sensitive to the cholesterol-depleting agents filipin and
      nystatin. The finding of this cholesterol-dependent Tf receptor internalization
      pathway through use of the small-molecule inhibitor sheds light on the
      pleiotropic nature of membrane trafficking dynamics and adds a complex dimension
      to our understanding of receptor regulation. Because of its unusual properties to
      inhibit iron uptake, we refer to NSC306711 as "ferristatin."

PMID- 18635002
TI  - Natural Sphingomonas glycolipids vary greatly in their ability to activate
      natural killer T cells.
AB  - Mouse natural killer T (NKT) cells expressing an invariant T cell antigen
      receptor (TCR) recognize glycosphingolipids (GSLs) from Sphingomonas bacteria.
      The synthetic antigens previously tested, however, were designed to closely
      resemble the potent synthetic agonist alpha-galactosyl ceramide (alphaGalCer),
      which contains a monosaccharide and a C18:0 sphingosine lipid. Some Sphingomonas
      bacteria, however, also have oligosaccharide-containing GSLs, and they normally
      synthesize several GSLs with different sphingosine chains including one with a
      cyclopropyl ring-containing C21:0 (C21cycl) sphingosine. Here we studied the
      stimulation of NKT cells with synthetic GSL antigens containing natural
      tetrasaccharide sugars, or the C21cycl sphingosine. Our results indicate that
      there is a great degree of variability in the antigenic potency of different
      natural Sphingomonas glycolipids, with the C21cycl sphingosine having
      intermediate potency and the oligosaccharide-containing antigens exhibiting
      limited or no stimulatory capacity.

PMID- 18635003
TI  - Potent and selective peptidyl boronic acid inhibitors of the serine protease
      prostate-specific antigen.
AB  - Prostate cancer cells produce high (microgram to milligram/milliliter) levels of
      the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active
      in the extracellular fluid surrounding prostate cancers but is found at 1,000- to
      10,000-fold lower concentrations in the circulation, where it is inactivated due
      to binding to abundant serum protease inhibitors. The exclusive presence of high
      levels of active PSA within prostate cancer sites makes PSA an attractive
      candidate for targeted imaging and therapeutics. A synthetic approach based on a
      peptide substrate identified first peptide aldehyde and then boronic acid
      inhibitors of PSA. The best of these had the sequence Cbz-Ser-Ser-Lys-Leu
      (boro)Leu, with a K(i) for PSA of 65 nM. The inhibitor had a 60-fold higher K(i)
      for chymotrypsin. A validated model of PSA's catalytic site confirmed the
      critical interactions between the inhibitor and residues within the PSA enzyme.

PMID- 18635004
TI  - Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating
      aptamer.
AB  - We show that a molecular scaffold can be utilized to convert a receptor binding
      aptamer into a receptor agonist. Many receptors (including tumor necrosis
      receptor family members) are activated when they are multimerized on the cell
      surface. Molecular scaffolds have been utilized to assemble multiple receptor
      binding peptide ligands to generate activators of such receptors. We demonstrate
      that an RNA aptamer that recognizes OX40, a member of the tumor necrosis factor
      receptor superfamily, can be converted into a receptor-activating aptamer by
      assembling two copies on an olignucleotide-based scaffold. The OX40 receptor
      activating aptamer is able to induce nuclear localization of nuclear factor
      kappaB, cytokine production, and cell proliferation, as well as enhance the
      potency of dendritic cell-based tumor vaccines when systemically delivered to
      mice.

PMID- 18635005
TI  - Identification of polyoxometalates as nanomolar noncompetitive inhibitors of
      protein kinase CK2.
AB  - Protein kinase CK2 is a multifunctional kinase of medical importance that is
      dysregulated in many cancers. In this study, polyoxometalates were identified as
      original CK2 inhibitors. [P2Mo18O62](6-) has the most potent activity. It
      inhibits the kinase in the nanomolar range by targeting key structural elements
      located outside the ATP- and peptide substrate-binding sites. Several
      polyoxometalate derivatives exhibit strong inhibitory efficiency, with IC50
      values < or = 10 nM. Furthermore, these inorganic compounds show a striking
      specificity for CK2 when tested in a panel of 29 kinases. Therefore,
      polyoxometalates are effective CK2 inhibitors in terms of both efficiency and
      selectivity and represent nonclassical kinase inhibitors that interact with CK2
      in a unique way. This binding mode may provide an exploitable mechanism for
      developing potent drugs with desirable properties, such as enhanced selectivity
      relative to ATP-mimetic inhibitors.

PMID- 18635006
TI  - Characterization of the azinomycin B biosynthetic gene cluster revealing a
      different iterative type I polyketide synthase for naphthoate biosynthesis.
AB  - Azinomycin B is a complex natural product containing densely assembled
      functionalities with potent antitumor activity. Cloning and sequence analysis of
      the azi gene cluster revealed an iterative type I polyketide synthase (PKS) gene,
      five nonribosomal peptide synthetases (NRPSs) genes and numerous genes encoding
      the biosynthesis of unusual building blocks and tailoring steps for azinomycin B
      production. Characterization of AziB as a 5-methyl-naphthoic acid (NPA) synthase
      showed a distinct selective reduction pattern in aromatic polyketide biosynthesis
      governed by bacterial iterative type I PKSs. Heterologous expression established
      the PKS-post modification route from 5-methyl-NPA to reach the first building
      block 3-methoxy-5-methyl-NPA. This proposed azinomycin B biosynthetic pathway
      sets the stage to investigate the enzymatic mechanisms for building structurally
      unique and pharmaceutically important groups, including the unprecedented
      azabicyclic ring system and highly active epoxide moiety.

PMID- 18635007
TI  - Bacterial base excision repair enzyme Fpg recognizes bulky N7-substituted-FapydG
      lesion via unproductive binding mode.
AB  - Fpg is a bacterial base excision repair enzyme that removes oxidized purines from
      DNA. This work shows that Fpg and its eukaryote homolog Ogg1 recognize with high
      affinity FapydG and bulky N7-benzyl-FapydG (Bz-FapydG). The comparative crystal
      structure analysis of stable complexes between Fpg and carbocyclic cFapydG or Bz
      cFapydG nucleoside-containing DNA provides the molecular basis of the ability of
      Fpg to bind both lesions with the same affinity and to differently process them.
      To accommodate the steric hindrance of the benzyl group, Fpg selects the adequate
      rotamer of the extrahelical Bz-cFapydG formamido group, forcing the bulky group
      to go outside the binding pocket. Contrary to the binding mode of cFapydG, the
      particular recognition of Bz-cFapydG leads the BER enzymes to unproductive
      complexes which would hide the lesion and slow down its repair by the NER
      machinery.

PMID- 18635009
TI  - Tryptophan aminopeptidase activity of several indole prenyltransferases from
      Aspergillus fumigatus.
AB  - Recently, five indole prenyltransferases from Aspergillus fumigatus have been
      proven biochemically to be responsible for prenylations of diverse substrates. In
      this study, we show peptidase activities of 7-DMATS, FgaPT1, CdpNPT, and FtmPT1,
      with preference for linear peptides containing a tryptophanyl moiety at the N
      terminus. Testing of 31 peptides revealed that these enzymes shared similar
      substrate specificity and accepted H-L-Trp-L-Ala-OH and H-L-Trp-Gly-OH as best
      substrates for aminopeptidase activity. By using H-L-Trp-Gly-OH as substrate, Km
      values at 350, 380, 300, and 420 microM and enzymatic rate constants kcat/Km at
      0.51, 0.24, 0.53, and 0.14 mM(-1)s(-1) were determined for 7-DMATS, FgaPT1,
      CdpNPT, and FtmPT1, respectively. In contrast to prenyltransferase activities,
      the aminopeptidase activities were strongly or completely inhibited by EDTA. Mn2+
      increased the aminopeptidase activities of FtmPT1 and CdpNPT up to 4- and 6-fold,
      respectively. To the best of our knowledge, this is the first report on the
      catalytic promiscuity of prenyltransferases.

PMID- 18635010
TI  - Glycosidase inhibition by macrolide antibiotics elucidated by STD-NMR
      spectroscopy.
AB  - A glycosynthase approach was attempted to glycodiversify macrolide antibiotics,
      using DesR, a family-3 retaining beta-glucosidase involved in the self-resistance
      mechanism of methymycin production. STD-NMR was used to probe enzyme-substrate
      interactions. Analysis of competitive STD-NMR experiments between erythromycin A
      and a chromogenic substrate (pNP-beta-d-glucose) with the hydrolytically inactive
      nucleophile mutants led us to discover a family of unprecedented glycosidase
      inhibitors. Analysis of kinetic data with wild-type DesR determined that
      erythromycin is a competitive inhibitor of the glucosidase (IC50 = 2.8 +/- 0.3
      microM and Ki = 2 +/- 0.2 microM) with respect to the hydrolysis of pNP-beta-d
      glucose. Comparable inhibitory data was obtained for clarithromycin; however, the
      inhibitory effect of azithromycin was weak and no significant inhibition was
      observed with methymycin or d-desosamine. This report documents significant
      inhibition of glycosidases by macrolide antibiotics and provides insight into the
      design of novel glycosidase inhibitors based on the macrolactone ring of
      macrolide antibiotics.

PMID- 18635008
TI  - Nanomolar CFTR inhibition by pore-occluding divalent polyethylene glycol-malonic
      acid hydrazides.
AB  - Inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR)
      chloride channel have potential application as antisecretory therapy in cholera.
      We synthesized mono- and divalent CFTR inhibitors consisting of a malonic acid
      hydrazide (MalH) coupled via a disulfonic stilbene linker to polyethylene glycols
      (PEGs; 0.2-100 kDa). IC50 values for CFTR inhibition were 10-15 microM for the
      monovalent MalH-PEGs, but substantially lower for divalent MalH-PEG-MalH
      compounds, decreasing from 1.5 to 0.3 microM with increasing PEG size and showing
      positive cooperativity. Whole-cell patch-clamp showed voltage-dependent CFTR
      block with inward rectification. Outside-out patch-clamp showed shortened single
      channel openings, indicating CFTR pore block from the extracellular side.
      Luminally added MalH-PEG-MalH blocked by >90% cholera toxin-induced fluid
      secretion in mouse intestinal loops (IC50 approximately 10 pmol/loop), and
      greatly reduced mortality in a suckling mouse cholera model. These conjugates may
      provide safe, inexpensive antisecretory therapy.

PMID- 18635011
TI  - A network of memory clinics: when and how?

PMID- 18635012
TI  - Revised research diagnostic criteria for Alzheimer's disease.

PMID- 18635013
TI  - Prothrombotic recombinant activated factor VII in intracerebral haemorrhage: FAST
      but not focused?

PMID- 18635014
TI  - Oral laquinimod for treatment of relapsing-remitting multiple sclerosis.

PMID- 18635015
TI  - Measurement of meaningful treatment effects in CADASIL.

PMID- 18635017
TI  - Shedding light on the role of poverty in brain development.

PMID- 18635018
TI  - Profile: John Morris: beating dementia through prevention.

PMID- 18635019
TI  - Biomarkers for cognitive impairment and dementia in elderly people.
AB  - The threat of a looming pandemic of dementia in elderly people highlights the
      compelling need for the development and validation of biomarkers that can be used
      to identify pre-clinical and prodromal stages of disease in addition to fully
      symptomatic dementia. Although predictive risk factors and correlative
      neuroimaging measures will have important roles in these efforts, this Review
      describes recent progress in the discovery, validation, and standardisation of
      molecular biomarkers--small molecules and macromolecules whose concentration in
      the brain or biological fluids can aid diagnosis at different stages of the more
      common dementing diseases and in the assessment of disease progression and
      response to therapeutics. An approach that efficiently combines independent
      information from risk-factor assessment, neuroimaging measures, and biomarkers
      might soon guide clinicians in the early diagnosis and management of cognitive
      impairment in elderly people.

PMID- 18635020
TI  - Diffusion-based tractography in neurological disorders: concepts, applications,
      and future developments.
AB  - Diffusion-based tractography enables the graphical reconstruction of the white
      matter pathways in the brain and spinal cord of living humans. This technique has
      many potential clinical applications, including the investigation of stroke,
      multiple sclerosis, epilepsy, neurodegenerative diseases, and spinal cord
      disorders, and it enables hypotheses to be tested that could not previously be
      considered in living humans. This Review will outline the limitations of
      tractography, describe its current clinical applications in the most common
      neurological diseases, and highlight future opportunities.

PMID- 18635021
TI  - Moderate and severe traumatic brain injury in adults.
AB  - Traumatic brain injury (TBI) is a major health and socioeconomic problem that
      affects all societies. In recent years, patterns of injury have been changing,
      with more injuries, particularly contusions, occurring in older patients. Blast
      injuries have been identified as a novel entity with specific characteristics.
      Traditional approaches to the classification of clinical severity are the subject
      of debate owing to the widespread policy of early sedation and ventilation in
      more severely injured patients, and are being supplemented with structural and
      functional neuroimaging. Basic science research has greatly advanced our
      knowledge of the mechanisms involved in secondary damage, creating opportunities
      for medical intervention and targeted therapies; however, translating this
      research into patient benefit remains a challenge. Clinical management has become
      much more structured and evidence based since the publication of guidelines
      covering many aspects of care. In this Review, we summarise new developments and
      current knowledge and controversies, focusing on moderate and severe TBI in
      adults. Suggestions are provided for the way forward, with an emphasis on
      epidemiological monitoring, trauma organisation, and approaches to management.

PMID- 18635023
TI  - Isolated severe vasculitic neuropathy revealing sarcoidosis.

PMID- 18635024
TI  - Distant and local recurrence in patients with biochemical failure after prostate
      brachytherapy.
AB  - PURPOSE: To analyze the patterns of failure after the brachytherapy management of
      localized prostate cancer. METHODS AND MATERIALS: From 1990 to 2008, 2869
      patients underwent prostate brachytherapy and 213 experienced a prostate-specific
      antigen (PSA) failure by the Phoenix definition. Of these 213 patients, 33.5%
      were low, 18.5% intermediate, and 58% high risk. RESULTS: Of the 119 patients
      biopsied, 36 (30%) had a least one positive posttreatment biopsy. In univariate
      and multivariate analyses, PSA doubling time was the most predictive of a
      positive biopsy. Patients with doubling times < or =3, >3-6, > or =6-10, and >10
      months had positive biopsy rates of 9%, 18%, 36%, and 42%, respectively (p=0.01).
      The actuarial rate of remaining free from distant metastases at 10 years was 73%.
      Patients with PSA doubling times of < or =3, >3-6, >6-10, and >10 months had
      freedom from distant metastases rates of 0%, 74%, 78%, and 94.5% at 10 years,
      respectively (p<0.0001). In multivariate analysis, PSA doubling time and time to
      PSA failure were the most significant predictors of developing distant
      metastases. CONCLUSIONS: About one third of patients harbor a component of local
      failure and one fourth demonstrate clinical metastases. PSA doubling time can be
      used to help predict the source of a rising PSA.

PMID- 18635022
TI  - NMDA receptors in clinical neurology: excitatory times ahead.
AB  - Since the N-methyl-D-aspartate receptor (NMDAR) subunits were cloned less than
      two decades ago, a substantial amount of research has been invested into
      understanding their physiological function in the healthy CNS. Research has also
      been directed at their pathological roles in various neurological diseases,
      including disorders resulting from acute excitotoxic insults (eg, ischaemic
      stroke, traumatic brain injury), diseases due to chronic neurodegeneration (eg,
      Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral
      sclerosis), disorders arising from sensitisation of neurons (eg, epilepsy,
      neuropathic pain), and neurodevelopmental disorders associated with NMDAR
      hypofunction (eg, schizophrenia). Selective NMDAR antagonists have not produced
      positive results in clinical trials. However, there are other NMDAR-targeted
      therapies used in current practice that are effective for treating some
      neurological disorders. In this Review, we describe the evidence for the use of
      these therapies and provide an overview of drugs being investigated in clinical
      trials. We also discuss new NMDAR-targeted strategies in clinical neurology.

PMID- 18635025
TI  - Optimization of high-dose-rate cervix brachytherapy applicator placement: the
      benefits of intraoperative ultrasound guidance.
AB  - PURPOSE: To promote efficient workflow for image-guided high-dose-rate (HDR)
      brachytherapy (BT) for cervix cancer by implementing intraoperative ultrasound
      (US) guidance for placement and optimization of intrauterine applicators. We
      sought to establish this as part of routine radiation oncology practice without
      radiology consultation. METHODS AND MATERIALS: Thirty-five consecutive insertions
      were performed in 21 women between July 2006 and March 2007. Cervical dilation,
      tandem selection and insertion were guided by transabdominal US. Final tandem
      position following vaginal applicator insertion was also confirmed by US.
      Computed tomography (CT) imaging was used for treatment planning and to assess
      perforation and applicator suitability for each patient anatomy. RESULTS:
      Intrauterine tandem insertion was successfully guided by US in the majority of
      procedures (34/35). CT imaging confirmed accurate placement within the uterine
      canal in each case, compared with a historic institutional perforation rate of
      10%. Visualizing patient anatomy during insertion altered the selection of tandem
      length and angle in 49% of cases, resulting in improved applicator matching to
      anatomy. Average insertion time significantly decreased from 34 to 26 minutes
      (p=0.01). Requests for assistance from gynecologic surgical oncology declined
      from 38% to 5.7% of procedures. CONCLUSIONS: Intraoperative US guidance for
      cervix BT has been successfully implemented with staff and equipment from
      radiation oncology. Using US during every insertion has led to improved
      applicator selection and placement while decreasing procedure time and reducing
      out of department consultations. These changes have eliminated repeat insertions
      due to unfavorable applicator placement (as revealed on postoperative CT), thus
      improving department efficiency and quality of patient care.

PMID- 18635026
TI  - Treatment of upper gum carcinoma with high-dose-rate customized-mold
      brachytherapy.
AB  - PURPOSE: To design an applicator for the treatment of tumors of the upper gum
      (UGCs) with high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A
      customized mold with four 6-Fr catheters was built. The two halves of the paired
      catheters form a functional loop without sharp curves. RESULTS: An adequate dose
      to the surface of the tumor is ensured. CONCLUSIONS: Mold-based HDR brachytherapy
      seems ideally suited for UGCs.

PMID- 18635027
TI  - Studies on encapsidated viroid-like RNA I. Characterization of velvet tobacco
      mottle virus.
AB  - Velvet tobacco mottle virus (VTMoV) isolated from Nicotiana velutina growing wild
      in arid Central Australia was transmitted by inoculation to a limited number of
      plant species of which N. clevelandii was the most convenient experimental host.
      The virus was also transmitted from field-grown plants toN. velutina and N.
      clevelandii by the mirid Cyropeltis nicotianae. VTMoV preparations purified by
      clarification with organic solvents and differential centrifugation contained
      polyhedral particles about 30 nm in diameter sedimenting as a single component at
      about 115 S. The particles were shown to be located in the nucleus, cytoplasm,
      and vacuoles of infected plant cells. Virus dissociated in the presence of
      mercaptoethanol and sodium dodecyl sulfate (SDS) separated into one major and two
      minor polypeptides with estimated molecular weights of 33,000, 36,000 and 31,000,
      respectively. Single-stranded RNA isolated from VTMoV by extraction with phenol
      was separated into five components with apparent molecular weights of 1.5 x
      10(6), 0.63 x 10(6), 0.25 x 10(6), 0.16 x 10(6), and 0.12 x 10(6) referred to as
      RNAs 1, 1a, 1b, 2, and 3, respectively. It appears that RNAs 1a and 1b are
      breakdown products of RNA 1, as shown elsewhere, and electron microscopic
      examination of the other species showed that whereas RNAs 1 and 3 are linear
      molecules, RNA 2 is circular. The similarity of RNAs 2 and 3 to the RNA of
      viroids is discussed. VTMoV has been compared with several RNA plant viruses with
      small polyhedral particles. Only solanum nodiflorum mottle virus appears to share
      some of its unique features and the two have been shown to be antigenically
      related.

PMID- 18635028
TI  - Studies on encapsidated viroid-like RNA. II. Purification and characterization of
      a viroid-like RNA associated with velvet tobacco mottle virus (VTMoV).
AB  - A viroid-like RNA has been purified from velvet tobacco mottle virus (VTMoV)
      capsids. This RNA exists as a covalently closed circular molecule of RNA as well
      as in a linear form with a molecular weight of approximately 1.2 x 10(5).
      Complementary DNA (cDNA) analysis indicates that the circular and linear forms of
      the viroid-like RNA contain indistinguishable nucleotide sequences and are unique
      RNA species. The viroid-like RNA has no nucleotide sequence homology with any
      other encapsidated RNAs and exhibits an absorbance-temperature profile, as well
      as nuclease sensitivities, typical of a viroid. The three other RNAs encapsidated
      in VTMoV virions were also investigated by cDNA analysis. Two of these
      (designated RNAs 1a and 1b, with molecular weights of 0.63 x 10(6) and 0.25 x
      10(6), respectively) are shown to be breakdown fragments of the largest RNA
      encapsidated by VTMoV (designated RNA 1) with a molecular weight of 1.5 x 10(6).

PMID- 18635029
TI  - Melting of viral RNA by coat protein: assembly strategies for elongated plant
      viruses.
AB  - The coat proteins of two rod-shaped plant viruses, papaya mosaic virus (PMV) and
      tobacco mosaic virus (TMV), have been tested for RNA melting activity. Under
      reconstitution conditions, PMV protein melts RNA in a noncooperative fashion.
      This activity is aspecific and is inhibited by low concentrations of NaCl as is
      virus reconstitution. TMV protein does not melt RNA either in the absence of NaCl
      or under reconstitution conditions at moderate ionic strength levels. The results
      suggest that elongated plant viruses have evolved at least two different assembly
      strategies in order to satisfy the requirement that the RNA within these viruses
      be in a melted configuration.

PMID- 18635030
TI  - Temperature-induced structural stabilization of the encapsidated RNA of southern
      bean mosaic virus and its biologic significance.
AB  - Virions of southern bean mosaic virus (SBMV) show two distinct sensitivity
      patterns upon heating. Infectivity loss and capsid denaturation occur
      concurrently if virions are exposed at 50-55 degrees in 0.1 M sodium phosphate
      buffer, pH 7.5, or 0.1 M glycine-phosphate buffer, pH 9.0. Contrastingly, virions
      are inactivated without any detectable capsid damage at 65-70 degrees in 0.1 M
      sodium phosphate buffer, pH 6.0, 0.1 M Tris-HCI buffer, pH 7.5, or 0.1 M glycine
      NaOH buffer, pH 9.0. Heat treatment causes no genomic degradation in these two
      situations; the divergent sensitivity of virions is due, apparently, to a
      differential thermal tolerance of the capsid protein to the buffer components
      and/or pH. SBMV-RNA isolated from virions inactivated at 65 degrees in 0.1 M Tris
      HCl buffer, pH 7.5, possesses low infectivity (1-2%). Observations based upon
      sucrose gradient sedimentation, temperature: absorbance relationship, and
      sensitivity to ribonuclease T(1) suggest that such RNA is structurally more
      compact and stable relative to that of the RNA from the nonheated virions.
      Neither the capsid protein nor the genome protein plays a direct role in the
      temperature-induced structural stabilization of SBMV-RNA in situ. If treated with
      8 M urea, 50% formamide or exposed at 55 degrees , the infectivity of RNA from
      the heat-inactivated SBMV is restored and is comparable to that of the RNA
      isolated from the nonheated virions. The observed mode of SBMV thermal
      inactivation, i.e., stabilization of RNA structure in situ, is unique among the
      viruses. Furthermore, these results suggest that the ability to initiate
      infection depends upon the secondary structure of the SBMV genome.

PMID- 18635031
TI  - In vivo pathway of Autographa californica baculovirus invasion and infection.
AB  - The pathway of Autographa californica nuclear polyhedrosis virus (AcNPV)
      infection in cabbage looper, Trichoplusia ni, larval midgut cells was studied by
      ultrastructural and virus titration methods. Enveloped virions interacted with
      microvilli of columnar cells resulting in apparent fusion of the viral envelope
      and microvillus membrane. After entry into the cell cytoplasm, the intact
      nucleocapsids appeared to enter the nucleus through nuclear pores, and uncoating
      of the viral genome took place in the nucleoplasm. Viral progeny were first
      observed at 8 hr postinoculation (p. i.) and the developmental cycle of the virus
      was essentially completed by 24 hr p.i. Inoculum virus nucleocapsids also moved
      to the basal plasma membrane and budded into the hemocoel through the basal
      lamina within 0.5 hr p.i. We propose that this budded virus, possessing an
      envelope with a peplomer structure, is the primary inoculum for the systemic
      invasion of the insect host.

PMID- 18635032
TI  - The bipartite genome of red clover necrotic mosaic virus.
AB  - Purified preparations of red clover necrotic mosaic virus isolated in Australia
      have been shown to contain three RNA components whose electrophoretic mobilities
      in polyacrylamide gel electrophoresis indicate molecular weights of 1.5 x 106
      (RNA 1), 0.5 x 10(6) (RNA 2), and 0.14 x 10(6) (RNA 3). Comparisons of the RNAs
      by hybridization analysis with 3H-labeled complementary DNAs synthesized in vitro
      have established that RNAs 1 and 2 are unique RNA molecular species with little
      or no sequence homology between them. However, RNA 3 appears to be a complex
      mixture of breakdown fragments of both RNA 1 and RNA 2. Infectivity experiments
      with highly purified preparations of RNAs 1 and 2 have demonstrated that both
      molecules are essential for infectivity.

PMID- 18635033
TI  - Development of systemic TMV infection in upper noninoculated tobacco leaves after
      differential temperature treatment.
AB  - A differential temperature treatment (DTT) of infected plants ensured a partial
      synchronization of the process of tobacco mosaic virus (TMV) infection. The
      "infectious entity" enters (and spreads to) basal areas of the upper
      noninoculated leaves held at low temperature, and then to a distal part of these
      leaves and basal sites of the lower leaves. The spread of the "infectious entity"
      over the vascular system of the upper leaves could be followed.

PMID- 18635034
TI  - Autographa californica nuclear polyhedrosis virus phosphoproteins and synthesis
      of intracellular proteins after virus infection.
AB  - Polypeptides and phosphoproteins isolated from nuclear and cytoplasmic fractions
      of TN-368-10 cells infected with Autographa californica nuclear polyhedrosis
      virus (AcMNPV) were analyzed by polyacrylamide gel electrophoresis. Likewise,
      AcMNPV extracellular virus and alkali-released virus were compared. ACMNPV
      extracellular virus possessed at least nine phosphoproteins while the alkali
      released virus had about 14 phosphoproteins. The major structural polypeptide of
      AcMNPV, polyhedrin, was phosphorylated. Intracellular proteins of infected TN-368
      10 cells were pulse-labeled with [35S]methionine and separated into nuclear and
      cytoplasmic fractions. At least 36 virus-induced polypeptides were detected in
      infected cells, and several polypeptides were found as early as 5 hr
      postinfection. The patterns of synthesis and appearance of infected cell
      polypeptides were complex, but polypeptide differences between nuclear and
      cytoplasmic fractions were detected. Twenty phosphoproteins labeled with 32P were
      also detected in the two fractions, and at least six had electrophoretic
      mobilities similar to virus-associated phosphoproteins.

PMID- 18635035
TI  - A striking change in symptoms on cucumber mosaic virus-infected tobacco plants
      induced by a satellite RNA.
AB  - The small RNA from cucumber mosaic virus (CMV) we had formerly referred to as RNA
      5 was shown to have a satellite nature similar to CARNA 5 (Kaper and Tousignant,
      1977, Virology 80, 186-195) and Sat-RNA (Mossop and Francki, 1978, Virology 86,
      562-566). Our satellite RNA has a great deal in common with CARNA 5 and Sat-RNA
      in many respects, except that its replication causes a striking change in
      symptoms on tobacco and on some species of Nicotiana infected with CMV. Large
      amounts of satellite RNA were found in RNAs of naturally occurring CMV isolates
      which induced a unique brilliant yellow symptom on tobacco. When purified
      satellite RNA was inoculated onto tobacco after being mixed with CMV isolates
      which contained no satellite RNA and which normally produced ordinary green
      mosaic symptoms, all of the infected tobacco developed the brilliant yellow
      symptom along with some symptom attenuation. Virions isolated from those plants
      contained much satellite RNA. CMV could be freed from satellite RNA by local
      lesion transfer and selection. Satellite RNA had substantial stability in vivo
      and in vitro. It caused the severe necrotic symptom or ultimate death of tomato
      like CARNA 5 but unlike Sat-RNA.

PMID- 18635036
TI  - Studies on encapsidated viroid-like RNA. III. Comparative studies on RNAs
      isolated from velvet tobacco mottle virus and Solanum nodiflorum mottle virus.
AB  - Solanum nodiforum mottle virus (SNMV) encapsidates two unique RNA species as
      shown by 3H-complementary DNA hybridization analysis. They are RNA 1, a long
      linear single-stranded molecule with a molecular weight of 1.5 x 10(6) and RNA 2
      and RNA 3 which are circular and linear forms of the same molecule, respectively.
      Electron microscopic examination and thermal denaturation studies indicate a
      viroid-like structure for RNA 2 of SNMV. Electrophoretic analysis of the viroid
      like RNA encapsidated by SNMV indicates it has a slightly larger molecular weight
      (0.13 x 108) than the viroid-like RNA recently isolated from velvet tobacco
      mottle virus (VTMoV). Complementary DNA (cDNA) analysis revealed that SNMV RNA 2
      contains the entire nucleotide sequence of VTMoV RNA 2, plus an additional 40-50
      nucleotides not present in the latter. Comparative sequence homology studies
      between the large RNAs encapsidated by SNMV and VTMoV (both of MW 1.5 x 10(6))
      revealed only partial homology (20%). However, the level of S1 nuclease
      resistance could be increased by the presence of higher salt concentrations
      during hybridization and subsequent S1 nuclease assay. This indicates that many
      smaller regions of homology are present between VTMoV RNA 1 and SNMV RNA 1. This
      is the second example of an encapsidated viroid-like RNA.

PMID- 18635037
TI  - Evidence for the absence of swelling of alfalfa mosaic virions.
AB  - The stability of the quaternary structure of bottom and top components of alfalfa
      mosaic virus (respectively AMV-B and AMV-Ta-t) in the pH range 5.5 to 7.8 and at
      ionic concentrations of 0.01 and 0.1 M has been investigated using small-angle X
      ray scattering and photon correlation spectroscopy. The X-ray scattering curves
      show no significant changes over the angular range measured (to a resolution of 1
      100 A (-1)) under the various solvent conditions; the radius of gyration of AMV
      Ta-t is constant at 113 +/- 3 A and the cross-sectional radius of gyration of AMV
      B constant at 69 +/- 2 A. The translational diffusion constants D(20m,w)(0) of
      AMV-B and AMV-Ta-t are also constant being, respectively, 1.09 (+/-0.01) x 10(-7)
      and 1.51(+/-0.02) x 10(-7) cm(2)/sec. The RNase sensitivities of AMV-B particles
      isolated at pH 6 or pH 7 were found to be similar. These results show that under
      a wide range of solvent conditions the gross morphology of AMV virions remains
      stable. Hence unlike a number of spherical plant viruses, AMV does not show the
      phenomenon of swelling.

PMID- 18635038
TI  - Plant cell suspension cultures sustain long-term replication of potato spindle
      tuber viroid.
AB  - Cell suspension cultures were established from tomato plants (Lycopersicum
      esculentum cv. "Rutgers") infected with either a severe (TPS cell line) or a mild
      (TPM cell line) strain of potato spindle tuber viroid (PSTV) and from uninfected
      plants (TH cell line). Based on measurements of packed cell volume, the TPS line
      exhibited a slower growth rate than the TH line, and reached lower levels of
      total cell volume during the stationary phase. The TPM line was intermediate
      between the other two. All the lines were highly polyploid (over 72 chromosomes).
      PSTV was detected consistently by electrophoretic analysis in both the TPS and
      TPM lines after more than 11/2 years of subculturing. Newly synthesized PSTV in
      actively dividing cells was detectable after 1 hr of [3H]uridine labeling (ca.
      0.1% of the radioactivity incorporated into total soluble RNA) and its proportion
      increased in subsequent samplings up to a steady state level of 0.24-0.28 or 0.31
      0.39% for TPM and TPS, respectively. Analysis on two-dimensional gels of proteins
      synthesized in the TH and TPS cell lines following incorporation of radiolabeled
      amino acids detected neither quantitative nor qualitative changes resulting from
      maintenance of viroid in the cell line.

PMID- 18635039
TI  - The serology of the bromoviruses. I. Serological interrelationships of the
      bromoviruses.
AB  - The serological relationships between brome mosaic (BMV), cowpea chlorotic mottle
      (CCMV), and broad bean mottle (BBMV) viruses, and their coat proteins, were
      studied by gel precipitin, "rocket immunoelectrophoresis" (RIE), and enzyme
      linked immunosorbent assay (ELISA) techniques. Gel precipitin and RIE tests
      indicated that capsid swelling altered the antigenicity of both BMV and CCMV, as
      although the coat proteins were serologically related at both pH 6.0 and pH 7.0,
      the viruses appeared to be related only when swollen at pH 7.0. Fixation of the
      viruses with 2% formaldehyde at pH 6.0 appeared to remove the relationship. BBMV
      was not related by precipitin tests to either BMV or CCMV but was related to both
      by direct and indirect ELISA at both pH 6.0 and pH 7.4, though less closely than
      BMV and CCMV were related to each other. Indirect ELISA showed the three coat
      proteins to be more closely related than the parent viruses. Formalinized BMV and
      CCMV appeared less related than the native viruses at pH 6.0. Sandwich ELISA
      proved too strain specific to show any group relationships. The implications of
      these results and a serological map proposed for the bromoviruses are discussed.

PMID- 18635040
TI  - Glycosylation of the cauliflower mosaic virus capsid polypeptide.
AB  - Evidence is presented for the glycosylation of the cauliflower mosaic virus
      (CaMV) capsid polypeptide. Fluorescent derivatives of concanavalin A (Con A) were
      shown to bind specifically to the dissociated CaMV capsid polypeptides in
      polyacrylamide gels. Con A also bound specifically to intact CaMV, so inhibiting
      the attachment of virus-specific antibodies. The role of carbohydrate residues in
      CaMV antigenicity is evaluated.

PMID- 18635041
TI  - Requirement of a genome-associated protein of tobacco ringspot virus for
      infectivity but not for in vitro translation.
AB  - Tobacco ringspot virus (TRSV) RNA incubated with Pronase to render it incapable
      of initiating infection retained its messenger activity in a wheat germ in vitro
      translation system. Furthermore, polypeptides synthesized by the Pronase-treated
      and untreated RNAs were indistinguishable.

PMID- 18635042
TI  - Lack of serological relationship between the 35K nonstructural protein of alfalfa
      mosaic virus and the corresponding proteins of three other plant viruses with a
      tripartite genome.
AB  - Alfalfa mosaic virus RNA 3 was translated in the mRNA-dependent rabbit
      reticulocyte cell-free system. The 35K translational protein was partly purified
      and used to raise antibodies. The antibodies obtained reacted with the 35K
      protein directed by AMV RNA 3 but not with the corresponding proteins directed by
      RNAs from three other viruses with a tripartite genome (tobacco streak, cucumber
      mosaic, and brome mosaic).

PMID- 18635043
TI  - Sequence heterogeneity in satellite tobacco necrosis virus RNA.
AB  - Satellite tobacco necrosis virus (STNV) RNAs isolated from early, middle, and
      late passage virus stocks were found to contain substantial and reproducible
      sequence variations which increased with passage of the virus. Several instances
      of clustered or correlated sequence changes were found. This sequence
      heterogeneity was detected by the use of the DNA oligomer-directed RNase H
      cleavage method. Terminally labeled RNA molecules were mapped with this method
      using synthetic DNA oligomers as sequence probes. RNA sequence analysis of RNase
      H fragments end labeled following DNA oligomer-directed RNase H cleavage also
      provided a direct way to examine sequence heterogeneity within the viral
      population.

PMID- 18635044
TI  - Secondary structure prediction of plant virus coat proteins.
AB  - Application of the secondary structure prediction techniques to the coat protein
      amino acid sequences of turnip yellow mosaic virus and satellite tobacco necrosis
      virus yielded an excellent correlation with the patterns of secondary structural
      elements observed in the capsid proteins of southern bean mosaic virus and tomato
      bushy stunt virus. Helical predictions for the very basic N-terminal regions of
      three plant viruses suggested modes of protein-nucleic acid interaction similar
      to those proposed for histones and protamines.

PMID- 18635045
TI  - A T = 1 capsid formed by protein of brome mosaic virus in the presence of
      trypsin.
AB  - In the presence of trypsin, the coat protein of brome mosaic virus (BMV) has been
      observed to polymerize in a D2O buffer at pD 7.6 to form a small empty capsid
      with triangulation number T = 1. Normally, this same protein polymerizes at
      acidic pH to form empty capsids with T = 3. The trypsin is shown to remove 63
      amino acids on the N terminus side leaving a polypeptide chain of Mr 13,500. The
      kinetics of formation of this small particle have been followed by neutron
      scattering. Further, the particle has been characterized by various physical
      methods: analytical centrifugation, quasielastic light scattering, and neutron
      scattering. It is found to have a radius of about 85-90 A, and a molecular weight
      of 760,000, in fair agreement with the value expected for a particle made of 60
      subunits of 13,500.

PMID- 18635046
TI  - Limited role of parental DNA in replication during infection by Bacillus subtilis
      phage SPO1.
AB  - When bacteria, growing in light medium, are infected with heavy phage, progeny
      DNA molecules band in the hybrid position only if they were synthesized using
      parental DNA as template. Thus, the rate of incorporation of radioactive
      precursors into hybrid DNA measures the use of parental template. This rate
      decreases with time during SPO1 infection, arguing against certain models for the
      control of SPOT replication.

PMID- 18635047
TI  - Okra mosaic virus empty protein shells in nuclei.
AB  - Okra mosaic virus produces large quantities (approximately 10 mg/g of tissue) of
      empty viral protein shells in inoculated cucumber cotyledons. Virus particles
      could not be detected in isolated nuclei, but empty protein shells accumulated
      there. At one day after inoculation, about half the total viral protein shells
      were found in the nucleus. This accumulation occurred in the presence of virus
      particles in the cytoplasm. The most likely explanation for this active and
      preferential accumulation is that viral coat protein enters the nucleus in the
      form of monomers or pentamers and hexamers, and is assembled into shells once
      inside.

PMID- 18635048
TI  - Analyses of Patois group bunyaviruses: evidence for naturally occurring
      recombinant bunyaviruses and existence of immune precipitable and nonprecipitable
      nonvirion proteins induced in bunyavirus-infected cells.
AB  - Shark River (SR) and Pahayokee (PAH) bunyaviruses (Patois serogroup, Bunyavirus
      genus, family Bunyaviridae) have almost identical L and S RNA oligonucleotide
      fingerprints, but M RNA fingerprints that are different, suggesting that the two
      viruses may represent naturally occurring reassortant viruses. These observations
      are in agreement with serological studies (B. N. Fields, B. E. Henderson, P. H.
      Coleman, and T. H. Work, 1969, Amer. J. Epidemiol., 89, 222-226) which have
      distinguished these two viruses by neutralization of infectivity tests
      (presumably reflecting differences in M RNA gene products, J. R. Gentsch, E. J.
      Rozhon, R. A. Klimas, L. H. El Said, R. E. Shope, and D. H. L. Bishop, 1980,
      Virology102, 190-204), but not by complement fixation tests (which probably
      relate to the viral N polypeptide coded by the S RNA, J. Gentsch, L. R. Wynne, J.
      P. Clewley, R. E. Shope, and D. H. L. Bishop, 1977b, J. Virol. 24,893-902). The
      3' terminal 11 nucleotides of PAH S RNA (3' (HO)OUCAUCAAAUGA ... 5') are
      identical in sequence to those of the S RNA species of snowshoe hare (SSH) and La
      Crosse (LAC) viruses, except for a position 7A residue which is a C residue in
      the SSH and LAC sequences. The major virion polypeptides of SR and PAH viruses
      include a nucleocapsid polypeptide (N, 22 x 10(3)) and two glycoproteins (PAH: G1
      118 x 10(3), G2, 35 x 10(3); SR: G1 113 x 10(3), G2, 35 x 10(3)). In SR-infected
      cells several immune precipitable polypeptides have been detected. These include
      11-, 54-, 64-, 93-, and 104 x 10(3)-dalton polypeptides. In addition, both SR and
      PAH viruses induce a 74 x 10(3)-dalton polypeptide (p74) that has not been
      detected in actinomycin D-treated infected cells, and is not immune precipitated
      from infected cell extracts.

PMID- 18635049
TI  - Studies on encapsidated viroid-like RNA. IV. Requirement for infectivity and
      specificity of two RNA components from velvet tobacco mottle virus.
AB  - Neither the virus-like RNA (RNA 1) nor the viroid-like RNA (RNA 2) of velvet
      tobacco mottle virus (VTMoV) is capable of independent replication in Nicotiana
      clevelandii. The function of RNA 2 for the RNA 1 replication could not be
      fulfilled by conventional viroids such as those of chrysanthemum stunt, citrus
      exocortis, or the viroid-like RNAs associated with avocado sunblotch and cadang
      cadang disease of coconut. Similarly, RNA 2 failed to replicate when coinoculated
      with RNAs of conventional viruses such as those of southern bean mosaic, sowbane
      mosaic, galinsoga mosaic, red clover necrotic mosaic, and carnation mottle, all
      of which possess genomes with molecular weights similar to those of VTMoV RNA 1.
      The interdependence of the two VTMoV RNAs for biological activity was so highly
      specific that the function of VTMoV RNA 2 could not be replaced by the viroid
      like RNA 2 from solanum nodiflorum mottle virus (SNMV), a closely related virus,
      for the replication of VTMoV RNA 1. Similarly, SNMV RNA 2 could not be replaced
      by VTMoV RNA 2 for the replication of SNMV RNA 1. These data support the view
      that RNA 2 cannot be a satellite RNA or an independent viroid. It seems that
      viruses such as VTMoV may have originated from associations of conventional
      single-stranded RNA viruses and viroids or, alternatively, may represent a stage
      in the evolution of viroids from viruses.

PMID- 18635050
TI  - A comparison of the nucleotide sequence homologies of three isolates of bean
      yellow mosaic virus and their relationship to other potyviruses.
AB  - 3H-labelled complementary DNA (cDNA) was reverse transcribed from the RNA of
      three biologically distinct isolates of bean yellow mosaic virus (BYMV-G, Q, and
      S) by the random primer method of Taylor et al. [Biochim. Biophys. Acta 442, 324
      330 (1976)]. Excess virus RNA was hybridized with each of the cDNAs and
      percentage hybrid formation was assayed using the single-strand-specific nuclease
      S1, The R0t (1/2) values obtained for the homologous hybridization reactions (1.2
      x 10(-2) mol sec liter(-1)) showed that all three BYMV-RNAs were unique species,
      without detectable zones of reiteration. Reciprocal hybridizations between
      isolates G, Q, and S have shown that each was significantly different from the
      other. A comparison of these three isolates with a selection of other potyviruses
      showed that the relationship between them was closer than that observed between
      any of them and the other potyviruses tested.

PMID- 18635051
TI  - Phage-induced development of a site-specific endonuclease in Anacystis nidulans,
      a cyanobacterium.
AB  - Anacystis nidulans infected by cyanophage AS-1 produces a site-specific
      endonuclease cleaving double-stranded DNA, as judged from the gel electrophoretic
      analysis of the reaction products and the determination of the terminal
      nucleotide at the 5'-end of the fragments. The enzyme was purified to near
      electrophoretic homogeneity. It has a molecular weight of 40,000 +/- 4,000. Only
      Mg2+ ions are required for enzyme activity. Limit digestion was not obtained even
      after extensive digestion of substrate DNA with large amounts of the purified
      enzyme. This suggests that the endonuclease splits the substrate at more than one
      nucleotide sequence with a different efficiency for each sequence. The following
      observations suggest that the endonuclease takes part in the breakdown of host
      DNA in the infected cell: purified host DNA is degraded by, while cyanophage AS-1
      DNA is protected against, the enzyme, and the appearance of the endonuclease
      during the lytic cycle coincides with the onset of intensive degradation of host
      DNA.

PMID- 18635052
TI  - The antiviral factor (AVF) from virus-infected plants induces discharge of
      histidinyl-TMV-RNA.
AB  - Crude preparations of the antiviral factor (AVF) exhibit also another activity
      measured by their ability to discharge histidinyl-TMV-RNA. The "discharging
      factor" (DF) is separable from AVF and the DF activity is released in AVF-treated
      leaves. AVF induces DF activity in leaves of Nicotiana glutinosa which carries
      the N-gene, as well as in the tobacco cultivar "Samsun" where the N-gene is
      absent. The DF activity is mediated by a transient low-molecular-weight compound,
      probably a polymerized ATP, which can be isolated from TMV-infected N. glutinosa
      leaves. A fraction capable of polymerizing ATP was indeed isolated from AVF
      treated leaf extracts, and the polymerized product was able to revive inactive DF
      preparations. A nuclease activity specific to crude AVF preparations is also
      reported. The similarity of the AVF to the interferon systems is discussed.

PMID- 18635053
TI  - Structure of the 19 S RNA transcript encoded by the cauliflower mosaic virus
      genome.
AB  - Turnip leaves infected with cauliflower mosaic virus accumulate several virus
      derived RNA species. These include a large transcript (>25 S) and a 19 S
      transcript. R-looping and diazo-cellulose filter hybridization techniques show
      that the 19 S RNA is derived from a contiguous segment of the CaMV genome which
      includes EcoR1-b and -d DNA fragments. This region encodes the synthesis of a
      nonvirion protein called P66. The 3' end of the 19 S transcript is polyadenylated
      and terminates near the single strand break in the alpha-strand of the genome.
      The 5' end of the transcript starts in or near the EcoR1-d fragment, near
      position zero on the map described by Hull and Howell (1978).

PMID- 18635054
TI  - Structural organization of Bacillus subtilis phage phi29. A model.
AB  - Phage phi29 is a nonisometric virus producing several types of morphological
      variants in normal infections. The study of these variants by electron
      microscopy, and their comparison with those from T-even phages, suggest that the
      capsid of phage phi29 is a prolate icosahedron. Phage phi29 capsid consists of a
      major protein, p8, and an additional protein, p8.5, making up the fibers. We have
      determined the number of subunits of each structural protein per viral particle
      taking into account the phage molecular weight (between 28 and 29.6 x 10(6)), the
      molecular weight of each structural protein, and the mass percentage of each
      protein with respect to the total protein mass of the phage. These values,
      together with the results obtained from chemical crosslinking of the structural
      proteins on the phage, suggest that the capsid contains protein p8 dimers
      clustered in trimers.

PMID- 18635055
TI  - The orderly, in vitro emergence of DNA from bacteriophage phi29 particles.
AB  - phi29 DNA-containing 12-13- particles (produced by infecting nonsuppressor hosts
      of Bacillus subtilis with phage containing suppressible mutations in cistrons 12
      and 13) can be complemented with lysates containing proteins p12* and p13 to
      yield infectious phage. Complementation of these particles with lysates
      containing p12* but not p13 or complementation with purified p12* in the absence
      of p13 produces a structure (called complex) which has a markedly different
      organization. Electron microscopy and sedimentation analysis after digestion with
      DNase I or proteinase K indicate that complex is composed of an intact phage head
      with a genome-sized linear DNA molecule attached at the collar-tail region. EcoRI
      digestion establishes that the DNA molecule has a unique orientation. Gel
      electrophoresis indicates that p12*, the neck appendage protein, is transferred
      to the particles when complex is formed. Complex can also be produced by
      incubation of 12-13- particles at 42 degrees , by incubation at pH 6.0, or by
      incubation in the presence of 20 mM EDTA. Complex is also formed from DNA
      containing 12- particles but to a lesser extent.

PMID- 18635056
TI  - Coat protein of potyviruses. I. Comparison of the four Australian strains of
      sugarcane mosaic virus.
AB  - As an aid to a more rational classification of the potyvirus group, we have
      examined the molecular weight, amino acid composition, and tryptic peptide map of
      the coat protein of four Australian sugarcane mosaic virus strains: Johnson grass
      (JG), sugarcane (SC), Queensland blue couch grass (BC), and sabi grass (Sabi).
      The proteins migrated as a single band in SDS-polyacrylamide gel electrophoresis
      with molecular weights of 33,700 (SC), 34,200 (JG), 39,100 (BC), and 40,300
      (Sabi). The BC and Sabi strains have identical amino acid compositions and
      tryptic peptide maps. The SC strain has a similar amino acid composition and
      tryptic peptide map but these two properties of the JG strain show very little
      similarity to the three other strains. On the basis of the coat protein
      properties investigated, we propose that the four sugarcane mosaic virus strains
      be subdivided into two groups: the sugarcane group containing SC, BC, and the
      Sabi strains and the Johnson grass group containing the JG strain.

PMID- 18635057
TI  - Transcription of cauliflower mosaic virus DNA. Detection of transcripts,
      properties, and location of the gene encoding the virus inclusion body protein.
AB  - We have detected several cauliflower mosaic virus transcripts in infected turnip
      leaves by northern-blot hybridization. These RNAs ranged in size from 0.9 to
      about 8 kb. Two species, a heterogeneous 7-to 8-kb RNA and a 2.3-kb RNA,
      accumulated radioactivity when CaMV-infected leaves were labeled with
      [32P]orthophosphate 20 days postinoculation. An abundant 62,000 MW polypeptide
      was synthesized in a rabbit reticulocyte lysate programmed with RNA from infected
      plants, but this polypeptide was absent when RNA from noninfected plants was used
      to direct translation. The 62,000 MW polypeptide was also the major in vitro
      product specified by virus-specific poly(A)+RNA purified by hybridization with
      CaMV DNA immobilized on DBM paper. The in vitro-synthesised 62,000 MW polypeptide
      was shown to be very similar to the major protein component of virus inclusion
      bodies by peptide fingerprint analysis. The 2.3-kb transcript is the mRNA
      encoding the 62,000 MW inclusion body protein. Crossed-contact hybridization
      mapping of this messenger on cloned CaMV DNA revealed that it is transcribed from
      the contiguous EcoR1 fragments d and b. The 7- to 8-kb RNA hybridized to all
      EcoR1 fragments and is probably a full-length primary transcript of the alpha-DNA
      strand.

PMID- 18635058
TI  - Comparative analysis of polypeptides synthesized in vivo and in vitro by two
      strains of barley stripe mosaic virus.
AB  - Proteins synthesized in a wheat germ system containing RNA from the Type or ND18
      strain of barley stripe mosaic virus (BSMV), or polyribosomes from Type or ND18
      infected barley, were compared with each other and with polypeptides from Type
      and ND18-infected plants. Polypeptides with apparent molecular weights (Mr) of
      25, 67, and 120 x 10(3) that were induced in infected barley were synthesized in
      vitro by polyribosomes from infected plants or RNA from purified BSMV. The 25,000
      Mr polypeptide was identified as BSMV coat protein by coelectrophoresis with coat
      protein from purified virions, by immunoprecipitation, and by absence of
      [35S]methionine incorporation into the protein. Strain-specific differences were
      observed in two additional translation products synthesized in both wheat germ
      and reticulocyte lysate systems containing Type of ND18 RNA. RNAs from both
      strains directed synthesis of 71 and 82 x 10(3) Mr polypeptides. However, ND18
      RNA directed synthesis of a larger amount of the 71,000 Mr polypeptide, whereas
      with Type RNA the 82,000 Mr polypeptide predominated. These two proteins may be
      processed in vivo because reduced synthesis of both polypeptides in wheat germ
      extracts containing polyribosomes from infected plants was correlated with
      increased synthesis of the 67,000 Mr polypeptide. Several additional polypeptides
      synthesized in the wheat germ system were probably premature termination products
      because their synthesis in the reticulocyte lysate was greatly reduced.

PMID- 18635059
TI  - A transcriptional map of the bacteriophage SP01 genome. I. The major early
      promoters.
AB  - Bacteriophage SP01 early transcripts come predominantly from the terminally
      repeated 12-kilobase-pair segments of its genome. Much less early RNA comes from
      a relatively large region of the genome which surrounds the early regulatory gene
      28. (The gene 28 protein positively regulates viral middle gene expression.) The
      major sites at which Bacillus subtilis RNA polymerase holoenzyme binds to SP01
      DNA and initiates RNA synthesis have been mapped and the direction of
      transcription from each of these promoter sites has been determined. There are 12
      such sites spanning 11.1 kilobase pairs at each end of the SP01 genome and each
      set of 12 sites defines a complex set of convergent transcription units.

PMID- 18635060
TI  - A transcriptional map of the bacteriophage SP01 genome: II. The major early
      transcription units.
AB  - The genome of the Bacillus subtilis phage SP01 contains a 12.6-kilobase-pair
      terminal redundancy. The transcription units in this region, which are utilized
      in vitro by B. subtilis RNA polymerase holoenzme, have been mapped. In vitro
      transcripts were separated and characterized by gel electrophoresis. Since there
      is such a large number of promoters in this region, it was necessary to employ
      conditions of transcription under which only subsets of all the transcripts would
      be made. Selective synthesis was achieved by transcription of restriction
      fragments containing a small number of promoters and by dinucleotide priming.
      Transcription units were mapped by observing the shortening of transcripts that
      resulted from restriction enzyme cleavage of the template. The mapping indicates
      the presence of two blocks of overlapping transcription units, oriented so as to
      yield convergent transcription toward a bidirectional termination region. The
      frequency of readthrough at the bidirectional terminator is low. Several partial
      termination sites of differing efficiencies have also been identified, including
      two that are active only at low ribonucleoside triphosphate concentrations. We
      also describe an effect of NaCl concentration on the migration of RNA in gels,
      which is specific for only two of the SP01 early transcripts. This effect may
      indicate unusual secondary structures for these two RNA molecules.

PMID- 18635061
TI  - Identification of a satellite RNA associated with turnip crinkle virus.
AB  - Turnip plants infected with turnip crinkle virus (TCV) contain four major RNA
      species which are not found in uninfected plants (A = 1.3 x 10(6) MW, B = 0.28 x
      10(6) MW, C = 0.17 x 10(6) MW, and D = 0.13 x 10(6) MW). At least two of these
      RNAs, RNA A and RNA C, are packaged in the mature virion, but only the large RNA
      A is required for infection. Plants infected with RNA A alone produce neither the
      small virion RNA C nor the small nonvirion RNAs B and D. The small virion RNA C
      is not infective by itself, but requires coinfection with RNA A to replicate in
      plants. RNA C increases the severity of symptoms in plants infected with RNA A
      and restores the production of the nonvirion RNAs B and D. T1 RNase
      oligonucleotide mapping and copy DNA hybridization analysis indicate that the
      virion RNAs A and C do not have extensive homology. These data suggest that the
      large virion RNA A contains the full TCV genome and that the smaller virion RNA C
      is a dispensible satellite, designated S-TCV.

PMID- 18635062
TI  - The architecture of the potexviruses.
AB  - The gross structural parameters describing particles of viruses of the Potex
      group are presented with particular reference to five hitherto unanalyzed
      definitive or putative members of the group. The new evidence in conjunction with
      published results for other members of the group leads to the hypothesis that all
      Potexviruses have essentially the same architecture. In particular, each particle
      has almost the same number of subunits per turn and that number is probably 9.
      The different viruses mainly differ in the fractional departure from n = 9 and in
      the size of the true repeats, values of 8 3/4 , 8 4/5 , 8 5/6 , 8 5/7 , 8 7/8 , 8
      9/10 , and 8 9/11 subunits per turn of the helices of the various viruses
      described here and/or previously being obtained.

PMID- 18635063
TI  - Timing of the synthesis of empty shells and minor nucleoproteins in relation to
      turnip yellow mosaic virus synthesis in Brassica protoplasts.
AB  - Following inoculation of Chinese cabbage protoplasts in vitro with turnip yellow
      mosaic virus, the development of characteristic changes in the chloroplasts was
      significantly asynchronous when observed by light or electron microscopy. In
      fully infected protoplasts there were only about 25% as many peripheral vesicles
      (the site of virus RNA synthesis) as in infected cells in the intact leaf. The
      yield of virus per infected protoplast was only about 1/10 th that found for an
      equivalent population of infected palisade cells from inoculated leaves. The
      production of empty protein shells was not reduced as much. Approximately equal
      amounts of virus nucleoprotein and empty protein shells were produced at all
      stages of the virus growth curve. However, if [35S]methionine was supplied when
      virus replication was well established, empty protein shells became labeled at an
      initial rate almost 10 times that of virus. Thus empty shells and virus must be
      assembled from differently located "pools" of protein subunits. The minor virus
      nucleoprotein fraction known to contain a substantial proportion of coat mRNA
      appears to be assembled earlier than the other minor nucleoprotein components,
      empty protein shells, or virus.

PMID- 18635064
TI  - Maize stripe virus: characteristics of a member of a new virus class.
AB  - An unusual filamentous nucleoprotein about 3 nm in diameter was consistently
      associated with maize stripe-diseased maize. Antiserum to purified nucleoprotein
      neutralized the infectivity of extracts from maize stripe-diseased plants
      suggesting that the nucleoprotein was the maize stripe virus (MStpV). The rate
      zonal sedimentation pattern of the nucleoprotein on sucrose gradients was
      polydisperse between 51 and 70 S. CsCl isopycnic centrifugation of combined
      nucleoprotein zones from sucrose gradients resulted in a single band of 1.28
      g/ml. The nucleoprotein consisted of 5.2% RNA and a single capsid protein of
      molecular weight 32,700 daltons. Large quantities of a noncapsid protein of
      molecular weight 16,300 daltons were also found in MStpV-infected tissue. MStpV
      was transovarially transmitted by its vector, Peregrinus maidis. Other species
      susceptible to MStpV in addition to Zea mays were Rottboellia exaltata and
      Sorghum bicolor. The similarities between MStpV and rice stripe virus are
      discussed. We conclude that these viruses represent a new virus class.

PMID- 18635065
TI  - Evidence that alfalfa mosaic virus infection starts with three RNA-protein
      complexes.
AB  - The tripartite genome of alfalfa mosaic virus (AMV) needs to be activated by its
      coat protein. To establish whether coat protein exerts its role by interacting
      structurally with one, two, or all three AMV-RNA species, the infectivity of
      mixtures of RNA-protein complexes with free RNAs were studied (Smit and Jaspars,
      Virology 104, 454-461, 1980). These studies were not fully conclusive since some
      redistribution of coat protein does occur as soon as RNAs are brought into
      contact with RNA-protein complexes. This problem was overcome by the use of ts
      mutants of AMV. Free ts coat protein subunits were not able to activate the wt
      genomic RNAs at 30 degrees in tobacco. Once complexed to the genomic RNAs at 0
      degrees , the biological activity of the ts coat protein remained when assayed at
      the nonpermissive temperature. Apparently, the ts coat protein is inactivated
      during attempted redistribution at 30 degrees . Studies of mixtures of RNA
      protein complexes and free RNA show that coat protein has to be present on at
      least two of the three RNA species. This result in combination with previous
      results (Smit and Jaspars, 1980) warrants the conclusion that the alfalfa mosaic
      virus infection starts with three RNA-protein complexes.

PMID- 18635066
TI  - Induction of a nonoccluded baculovirus persistently infecting Heliothis zea cells
      by Heliothis armigera and Trichoplusia ni nuclear polyhedrosis viruses.
AB  - A nonoccluded singly enveloped baculovirus (baculovirus X) persistently infects
      Heliothis zea (IMC-HZ-1) cells in culture. Singly enveloped nuclear polyhedrosis
      viruses from H. zea and Heliothis armigera, and multiply enveloped nuclear
      polyhedrosis viruses from Trichoplusia ni, Spodoptera frugiperda, and Spodoptera
      littoralis were all found to induce baculovirus X. Experiments are reported which
      use metabolic inhibitors and inactivated inducing virus to show that it is
      probable that a structural component of the virus, most likely a protein, is
      responsible for inducing baculovirus X. The persistent virus is induced to
      replicate by uv-inactivated virus but not by heat-inactivated inducing virus. The
      virus is not induced to replicate by a number of metabolic inhibitors in the
      absence of an inducing virus. Inhibition of transcription and translation
      prevents the induction of the persistent virus by an inducing virus. Inhibition
      of DNA replication has no effect on the induction of the virus. This suggests
      that the persistent virus genome is present in abundance in all cells.

PMID- 18635067
TI  - Investigation of genetic heterogeneity in wild isolates of Spodoptera frugiperda
      nuclear polyhedrosis virus by restriction endonuclease analysis of plaque
      purified variants.
AB  - Spodoptera frugiperda nuclear polyhedrosis virus (SfMNPV was obtained from four
      different sources and each isolate was cultured in IPLB-SF21 cells. Viral DNA
      from each isolate was analyzed with EcoR1, Xho1, and BamH1 restriction
      endonucleases. All four isolates could be distinguished on the basis of minor
      differences in EcoR1 patterns. Submolar DNA restriction fragments were seen in
      all isolates indicating that each isolate consisted of a mixture of different
      genotypes. To investigate this, two of the isolates were plaque purified. Of the
      total of 13 clones isolated, the DNA from 5 of these had distinctly different
      EcoR1 restriction endonuclease patterns. The five cloned variants were further
      analyzed with Xho1, BamH1, and Sac1. Three of the five clones had fragments which
      comigrated with submolar fragments seen in the wild isolates. Thus, the submolar
      fragments observed in digests of the DNA from two wild isolates of SfMNPV were
      due to a mixture of genetic variants.

PMID- 18635068
TI  - Towards a system for the identification and classification of potyviruses. II.
      Virus particle length, symptomatology, and cytopathology of six distinct viruses.
AB  - The mean particle lengths of lettuce mosaic virus (LMV), bean common mosaic virus
      (BCMV), passionfruit woodiness virus (PWV), potato virus Y (PVY), sugarcane
      mosaic virus (SCMV), and one strain of bean yellow mosaic virus (BYMV) were all
      shown to be close to 750 nm. However, the length of two other serologically
      closely related strains of BYMV, variants of pea mosaic virus referred to as PMV
      and SPMV, had significantly longer particles, about 792 and 842 nm. Each of the
      distinct viruses had readily distinguishable host ranges. The strains of BYMV
      could also be distinguished from each other although they had many hosts in
      common with similar symptoms. Electron microscopy of plant cells infected by the
      viruses studied showed that the cell inclusions induced by infection were of two
      readily distinguishable types although some minor virus-specific differences were
      also observed. The BYMV strains and LMV induced long "relaxed" pinwheel
      inclusions whereas those induced by BCMV, PWV, PVY, and SCMV were shorter,
      "tighter," and curved. The significance of these observations to problems of
      potyvirus identification and classification is discussed.

PMID- 18635069
TI  - Cucumber mosaic virus-associated RNA 5. VII. Double-stranded form accumulation
      and disease attenuation in tobacco.
AB  - The double-stranded (ds) form of cucumber mosaic virus (CMV)-associated RNA 5
      (CARNA 5), which accumulates in unusually large proportions in CMV-infected
      Xanthi nc tobacco plants, could be identified directly in buffer extracts of
      these plants via its reaction with poly(I):poly(C) or poly(A):poly(U) antisera in
      two-dimensional immunodiffusion tests. After infiltration of CMV-infected tobacco
      tissues with 4'-aminomethyltrioxalen, followed by irradiation with long
      wavelength ultraviolet light, a certain proportion of the dsCARNA 5 was recovered
      in a crosslinked state. This showed that in all probability a major proportion of
      the accumulated (+) and (-) strands of CARNA 5 occurs intracellularly in ds form
      and that dsCARNA 5 is not an artifact of phenol extraction. In differential
      temperature inoculated tobacco leaves, in which virus multiplies
      semisynchronously, dsCARNA 5 continued to accumulate after the biological
      activities attributable to virus and CARNA 5 were declining steeply. In tobacco
      plants systemically infected with CMV strain P6, which produced very distinct
      symptoms in individual leaves as well as the characteristic alteration of layers
      of symptomatic and symptomless leaves, dsCARNA 5 was usually detected in
      symptomless tissues but virus was not. Also, in other tissues and organs of such
      plants the presence of dsCARNA 5 was generally inversely correlated with that of
      virus. In all likelihood, the accumulation of dsCARNA 5 is the manifestation of a
      mechanism which regulates disease expression and resistance in CMV-infected
      plants.

PMID- 18635070
TI  - The RNAs of cucumoviruses: 3'-terminal sequence analysis of two strains of tomato
      aspermy virus.
AB  - The sequences of 189 residues from the 3' terminus of three RNAs of one strain
      and two RNAs of another strain of tomato aspermy virus have been determined;
      there was almost complete sequence homology between the RNAs. A base-paired
      transfer RNA-like structure is proposed for tomato aspermy virus RNAs which is
      similar in many aspects to the structure proposed for the 3'-terminal 172
      residues of RNA 4 of the Q-strain of cucumber mosaic virus (R. H. Symons, Nucleic
      Acids Res.7, 825-837, 1979). These 172 residues of cucumber mosaic virus RNA 4
      can be aligned to show 73% sequence homology with the 3'-terminal 189 residues of
      the tomato aspermy virus RNAs.

PMID- 18635071
TI  - Purification and characterization of a virus from the aphid Rhopalosiphum padi.
AB  - A 27-nm icosahedral virus was purified from the oat bird cherry aphid,
      Rhopalosiphum padi (L.). The virus had an s(20,w) of 162 +/- 2 S, and bouyant
      densities of 1.37 in CsCl and 1.35 in Cs2SO4. It contained one ssRNA of 31 +/- 2
      S and three major proteins. The relationship of the R. padi virus to other small
      RNA invertebrate viruses is unclear.

PMID- 18635072
TI  - The RNA of tobacco etch virus: further characterization and detection of protein
      linked to RNA.
AB  - TEV-RNA was separated into poly(A)+ and poly(A)- RNA by affinity chromatography.
      Both classes of RNA have similar base ratios. The poly(A) segment in the RNA was
      shown to be located at the 3'-OH end by dihydroxyborylaminoethyl-cellulose
      chromatography. Although the poly(A) was heterodisperse in length, ranging from
      about 200 to less than 33 AMP residues, two size classes averaging about 150 and
      30 AMP residues, respectively, could be recognized. The presence of a genome
      linked protein of molecular weight 6000 daltons was detected. The viral RNA is
      infectious even after proteinase K treatment, indicating that the genome-linked
      protein is not required for infectivity.

PMID- 18635073
TI  - The polypeptides induced in Drosophila cells by Drosophila C virus (strain
      Ouarzazate).
AB  - The Ouarzazate strain of Drosophila virus (DCV0) was grown in Drosophila
      melanogaster tissue culture cells, and [35S]methionine-labeled virions were found
      to contain a group of major structural proteins with a molecular weight of
      approximately 30,000 as well as several minor proteins of higher molecular weight
      and a protein of approximately 10,000 daltons. Using a range of pulses, chases
      and gel systems, examination of the intracellular proteins induced by DCV0 showed
      the presence of 17 polypeptides not found in uninfected cells. The synthesis of
      virus-induced polypeptides was extremely asymmetric with a rapid appearance of
      the major virus structural proteins and a much slower appearance of the lowest
      molecular weight structural protein (VP4). Processing of virus-induced proteins
      including the appearance of VP4 was demonstrated using pulse-chase after pulsing
      with [35S]methionine. While the highest molecular weight induced protein found in
      infected cells was 146,000, pretreatment of cells with iodoacetamide resulted in
      the appearance of a protein with a molecular weight of approximately 200,000. The
      evidence presented in this paper supports the inclusion of DCV0 in the
      Picornaviridae group.

PMID- 18635074
TI  - Ultraviolet mapping of RNA transcripts encoded by the cauliflower mosaic virus
      genome.
AB  - The transcription of the cauliflower mosaic virus (CaMV) genome was analyzed by
      ultraviolet (uv) mapping procedures to determine promoter sites and polarity of
      synthesis of "late" viral RNA transcripts. The late transcripts include two
      major, discrete polyadenylated RNAs, a large full-genome-length transcript and a
      19 S RNA, and nonpolyadenylated RNA fragments smaller than the full-genome-length
      transcript. All late transcripts are derived from one strand of the CaMV genome,
      the alpha strand. When protoplasts were irradiated with increasing uv doses, the
      ability of the CaMV genome to support the synthesis of viral RNA was lost in a
      polar fashion. The EcoR1 fragments of the CaMV genome in order of decreasing uv
      sensitivity were a1, a2, c, then b. The uv sensitivity data coupled with other
      observations are most consistent with a model in which CaMV transcription is
      promoted from two sites-one near EcoR1-d and the other counterclockwise to the
      single-strand interruption in the alpha strand in the BglII subfragment c of
      EcoR1-b. The data do not fit a model in which transcription is promoted from one
      site, just clockwise from the alpha strand interruption site.

PMID- 18635075
TI  - Attempts to obtain Oryctes baculovirus replication in three insect cell cultures.
AB  - Attempts were made to obtain Oryctes baculovirus replication in three insect cell
      cultures. The cell cultures were derived from the dynastine beetle Heteronychus
      arator, the fall armyworm Spodoptera frugiperda, and the mosquito Aedes
      albopictus. The criteria for virus replication were synthesis of virus-specific
      DNA and presence of virus particles within cells. Infection occurred in H. arator
      cells but not in S. frugiperda cells. When A. albopictus cells were inoculated
      with high concentrations of Oryctes baculovirus virus uptake and syncytia
      formation occurred but there was no evidence of virus replication and thus
      infection probably did not occur. It is suggested therefore that a previous
      report of replication of Oryctes baculovirus in both S. frugiperda and A.
      albopictus cells is incorrect and an alternative interpretation of this report is
      proposed.

PMID- 18635076
TI  - Nucleotide sequence of naturally occurring deletion mutants of cauliflower mosaic
      virus.
AB  - The DNAs of two isolates of strain CM4-184 of cauliflower mosaic virus, reported
      by other investigators to have deletions in different locations of the region II
      region III portion of the genome, were found to give identical fragments when
      cleaved with BglII, BamHI, and HindIII restriction endonucleases. When these
      isolates of CM4-184 were cloned into the single-stranded vector M13mp7 followed
      by nucleotide sequence analyses, they had identical sequences. Comparison of the
      sequences of such CM4-184 deletion mutants with an undeleted strain of similar
      origin (strain CM1841) revealed that the CM4-184 deletion consists of 421 base
      pairs from open coding region II of the genome. Therefore region II, comprised of
      about 500 base pairs, is not essential for infectivity. It may represent a site
      at which foreign DNA could be inserted into the genome.

PMID- 18635077
TI  - Different helper factors associated with aphid transmission of some potyviruses.
AB  - Myzus persicae transmitted watermelon mosaic virus (WMV) after acquiring it
      through artificial membranes from a solution of purified virus mixed with the
      soluble fraction from infected leaf extracts or by prefeeding on the soluble
      fraction before acquiring purified virus. WMV-induced helper factor assisted M.
      persicae in transmitting purified turnip mosaic virus (TuMV) but not potato virus
      Y (PVY). TuMV-induced helper factor from infected leaves was ineffective for the
      transmission of purified WMV or PVY. PVY-induced helper factor from infected
      leaves was capable of helping the transmission of TuMV but not that of WMV. The
      results indicate that there are at least three distinct helper factors with
      different specificity associated with potyviruses.

PMID- 18635078
TI  - Biochemical properties of a persistent nonoccluded baculovirus isolated from
      Heliothis zea cells.
AB  - A persistent nonoccluded rod-shaped nuclear virus of Heliothis zea (IMC-Hz-1-NOV)
      was isolated from Trichoplusia ni cells (Tn-368) by sucrose density gradient
      centrifugation. The molecular weights of IMC-Hz-1-NOV structural proteins were
      determined by SDS-polyacrylamide gel electrophoresis. Separation of IMC-Hz-1-NOV
      DNA restriction fragments by agarose gel electrophoresis gave an approximate DNA
      molecular weight of 132 x 10(6). Digestion of double-stranded IMC-Hz-1-NOV DNA
      with HindIII and BamHI revealed a cleavage pattern different from the patterns of
      H. zea NPV and H. armigera NPV.

PMID- 18635079
TI  - Viral protein synthesis in barley protoplasts inoculated with native and
      fractionated brome mosaic virus RNA.
AB  - When barley protoplasts were inoculated with brome mosaic virus (BMV) RNAs 1 and
      2, there was a pronounced synthesis of the 110,000- and 100,000-dalton virally
      coded proteins. In contrast, there was no detectable synthesis of any viral
      proteins following inoculation with RNA 3 alone or RNA 4 alone. When RNAs 1 and 2
      were recombined with RNA 3 in the inoculum, the profile of proteins synthesized
      was identical to that following inoculation with similar quantities of
      unfractionated BMV RNA; i.e., the 35,000-dalton virally coded protein and coat
      protein were synthesized in addition to the two high-molecular-weight viral
      polypeptides. RNAs 1 and 2 were shown not to be selectively bound (in preference
      to RNAs 3 or 4); hence, these data reveal that one or both of these RNAs encode
      proteins involved in early events of infection, perhaps replication.

PMID- 18635080
TI  - Cucumber mosaic virus-induced RNA replicase: solubilization and partial
      purification of the particulate enzyme.
AB  - Cucumber seedlings infected with cucumber mosaic virus (CMV) contain a virus
      induced RNA-dependent RNA polymerase (RNA replicase) in both soluble and
      particulate fractions of plant extracts; no such activity is found in uninfected
      plants. The extensive purification and characterization of the soluble RNA
      replicase has been described (R. Kumarasamy and R. H. Symons, 1979, Virology 96,
      622-632) while the characterization of the particulate enzyme is reported here.
      The particulate RNA replicase was solubilized-by incubation in 150 mM MgS04 at 37
      degrees for 5 min; both magnesium and sulfate ions were required for maximum
      release. Only 5-7% of the protein of the particulate fraction was released under
      these conditions either in the presence or absence of a variety of salts. The
      solubilized enzyme was purified about 60-fold by a three-step procedure to a
      specific activity similar to that of the 10,000-fold purified soluble enzyme. CMV
      RNA and poly(C)-copying activities copurified through the three steps.
      Purification was followed by polyacrylamide gel electrophoresis in the presence
      of sodium dodecyl sulfate of the in vitro 3H-labeled proteins. The most prominent
      virus-induced components were two proteins of Mr 100,000 and 110,000 which
      correspond in size to two virus-induced proteins in the extensively purified
      soluble RNA replicase. The Mr 110,000 protein comigrated with the full length in
      vitro translation product of CMV RNA 2 while the Mr 100,000 was detectably larger
      than the full length in vitro translation product of CMV RNA 1.

PMID- 18635081
TI  - Homology in the 3'-terminal regions of different barley stripe mosaic virus RNA
      species.
AB  - Preparations of [3H]DNA complementary to the individual species of barley stripe
      mosaic virus (BSMV) RNA (cDNA) about 1000 nucleotides long were obtained using
      avian myeloblastosis virus reverse transcriptase and oligo(dT)10 primer. These
      cDNAs were used in kinetic hybridization experiments to study the sequence
      homology between the 3'-terminal regions (not including 150-200 nucleotides
      adjacent to the 3'-end) of individual BSMV RNA species. These regions in RNA 2
      and 3 are highly homologous and have no sequences in common with the respective
      region in RNA 1.

PMID- 18635082
TI  - Aminoacylation of barley stripe mosaic virus RNA: polyadenylate-containing RNA
      has a 3'-terminal tyrosine-accepting structure.
AB  - Barley stripe mosaic virus (BSMV) RNA which was previously reported to contain
      poly(A) sequences (Agranovsky et al., 1978) can be specifically esterified with
      tyrosine in vitro in the presence of an aminoacyl-tRNA synthetase fraction from
      wheat embryos. All the three RNA components of the BSMV strain with a three
      component genome (Norwich) and both RNA components of a two-component strain
      (Russian) can be tyrosylated. The poly(A)-containing (bound to oligo(dT)
      cellulose) and poly(A)-deficient (not bound to oligo(dT)-cellulose) fractions of
      BSMV RNA display a similar amino acid-accepting ability. The nucleotide sequence
      which accepts tyrosine is coupled with the intact genomic polyadenylated BSMV
      RNA. The viral RNA isolated after sucrose density gradient centrifugation under
      drastic denaturing conditions retains its aminoacylating activity, which suggests
      that this activity is not due to the presence in a BSMV RNA preparation of a
      tyrosine tRNA associated with BSMV RNA. Inhibition of aminoacylation of the 3'
      oxidized (treated with sodium metaperiodate) BSMV RNA suggests that the tyrosine
      accepting structure is localized at the 3' terminus of BSMV RNA molecules. It is
      shown that segments of different lengths obtained upon random fragmentation can
      be tyrosylated. The 3'-terminal (tyrosine-accepting) poly(A)+ segments can be
      isolated. The shortest segments of viral RNA capable of being aminoacylated
      [i.e., containing both tRNA-like structure and poly(A)] consists of approximately
      150-200 nucleotides. The analysis of the oligonucleotides derived from individual
      BSMV RNA components labeled with (32)P at the 3' end revealed two types of 3'
      terminal sequences different from poly(A). It is suggested that a poly(A)
      sequence is intercalated between a 3'-terminal tyrosine-accepting structure and
      the 5'-terminal portion of poly(A)+ BSMV RNA.

PMID- 18635083
TI  - The detection and characterization of viral-related double-stranded RNAs in
      tobacco mosaic virus-infected plants.
AB  - The 2 M LiCl-soluble RNA fraction extracted from tobacco mosaic virus (TMV)
      infected tobacco plants contains, in addition to the viral replicative form of 4
      x 10(6) MW, three smaller double-stranded (ds) RNA species with apparent
      molecular weights (estimated by polyacrylamide gel electrophoresis, using ds RNAs
      as markers) of 2.25, 1.1, and 0.23 x 10(6). The synthesis of all four ds RNAs is
      insensitive to actinomycin D. They are completely RNase insensitive at high salt
      concentrations and are found both in directly inoculated and in apical tissues.
      In tissues incubated in the presence of 3H-uridine and actinomycin D, the three
      small ds RNAs accounted for 6 to 11.5% of the total radioactivity incorporated
      into viral ds RNA. On a molar basis, however, in apical leaves the smallest ds
      RNA was synthesized to almost the same level as the replicative form. By
      molecular hybridization, the three small ds RNAs have been shown to be of viral
      origin, and each contains sequences represented in the 5' end of complementary
      (negative strand) TMV RNA. Based on molecular weight data, none of the ds RNAs
      can be considered to be a ds form of the subgenomic TMV coat protein mRNA (the
      LMC), suggesting that it is not replicated independently. None of the small ds
      RNAs was found to be an endogenous product of the bound TMV RNA replicase.

PMID- 18635084
TI  - The molecular organization of beet necrotic yellow vein virus.
AB  - Isolates of beet necrotic yellow vein virus (BNYVV) contain rod-like virus
      particles of four different lengths. Using electron microscopy in combination
      with optical diffraction and digital image processing methods, we have determined
      their structural organization. All particles observe the same helical symmetry,
      according to which the coat protein molecules (Mr approximately 21,000) follow a
      single-stranded right-handed helix of pitch 2.6 nm. This helix has an axial
      repeat of four turns, involving 49 protein subunits. The different particle
      lengths are apparently dictated by the four RNA species which compose the
      segmented BNYVV genome, with four nucleotides protected by each coat protein
      subunit. The spatial arrangement of BNYVV RNA--49 residues per helical turn,
      pitch = 2.6 nm--is virtually identical to that of tobacco mosaic virus (TMV) RNA
      (49 residues per turn, pitch = 2.3 nm), although the helical packing of protein
      (49/3 subunits per turn) and RNA-to-protein stoichiometry (3 bases per subunit)
      of TMV are significantly different from those of BNYVV (49/4 subunits per turn
      and 4 bases per subunit, respectively).

PMID- 18635085
TI  - The molecular weight and packaging of dsRNAs in the mycovirus from Ustilago
      maydis killer strains.
AB  - The mycoviruses of Ustilago maydis killer strains are isometric, 43 nm in
      diameter, and contain several dsRNA segments designated heavy (H), medium (M),
      and light (L) according to their relative size. To determine the number of dsRNA
      segments per virion, major sedimenting and density components were isolated,
      their molecular weights determined from hydrodynamic properties, and their dsRNA
      contents determined by electron microscopy and/or polyacrylamide gel
      electrophoresis. The H dsRNA segments of 2.9, 3.1, and 4.2 x 10(6) daltons are
      separately encapsidated in isometric capsids that band in CsCI at 1.383, 1.394,
      and 1.418 g/cm8, respectively. The P1 strain contains the 3.1 and 4.2 x 10(6)
      dalton segments, and the 3103 strain contains the 2.9 and 4.2 x 106-dalton
      segments. The T-4 strain contains the 3.1 x 106-dalton H segment and two M
      segments of 0.67 and 0.60 x 10(6) daltons. The H segments are separately
      encapsidated in virions which banded at 1.394 g/cm8, whereas the M segments are
      encapsidated in sets of one, two, or three in virions which banded at 1.314,
      1.341, and 1.370 g/cm8. Molecular weights of 9.8 and 13.0 x 106 daltons were
      calculated for empty capsids (pCsCl = 1.278 g/cm8) and capsids containing the 3.1
      x 10(6)-dalton dsRNA segments (pCsCl = 1.394 g/cm8). Analysis of components that
      banded at other densities in CsCl were consistent with the hypothesis that the
      banding pattern is the result of the encapsidation of a finite number of dsRNA
      segments in a capsid of 9.8 x 106 daltons. Although one to three M dsRNA segments
      were encapsidated in a single virion, no particles were detected with more than
      one H dsRNA segment per virion.

PMID- 18635086
TI  - Mapping of the two coat protein genes on the middle RNA component of squash
      mosaic virus (comovirus group).
AB  - Squash mosaic virus, a member of the comovirus group, has a divided genome
      identified as middle-component RNA (M RNA; MW = 1.4 x 10(6)) and bottom-component
      RNA (B RNA; MW = 2 x 108). The isometric capsid of squash mosaic virus is
      composed of two distinct protein monomers with molecular weights of 22,000 (22k)
      and 42k. The isolated RNA components were translated in a rabbit reticulocyte
      lysate system. Translation products of the B RNA had estimated molecular weights
      of 190k, 51k, and 32k, while the M RNA products ranged in estimated molecular
      weight from 22k to 112k. Products of the B RNA did not react with antisera
      prepared to the 22k and 42k coat proteins. All of the M RNA products reacted with
      antiserum to the 22k coat protein and all the products larger than 35k reacted
      with antiserum to the 42k coat protein. The 22k product of M RNA translation had
      a V-8 protease peptide pattern identical to that of the 22k coat protein.
      Protease peptide patterns of the M RNA 64k and 112k-105k translation products
      showed a number of peptide fragments similar to those produced by the 22k and 42k
      coat proteins, indicating that the translation products contained the sequences
      of the two coat proteins. The proposed gene order of translation for squash
      mosaic virus M RNA is as follows: 5' end-22k coat protein gene-42k coat protein
      gene-48k unidentified protein gene-untranslated sequence-3' end.

PMID- 18635087
TI  - The polar alkaline disassembly of papaya mosaic virus.
AB  - The disassembly of papaya mosaic virus (PMV) at alkaline pH (pH 10) was monitored
      by following the decrease of turbidity at 320 nm and by electron microscopy. Most
      of the virion particle population undergoes a sequential loss of protein subunits
      starting exclusively from the 3'OH end of the RNA, but a small fraction resists
      degradation. The progressive decrease in size distribution suggests a sequential
      process and the presence of "brush-like" structures at one end of the virus
      particle favors a polar model for disassembly. Furthermore, after treatment with
      nucleases to digest the exposed RNA tails, the 5' cap structure (m7GpppGp) was
      found to be conserved in the remaining nucleoprotein intermediates. This
      indicates that the disassembly of PMV occurs from the 3' terminus to the 5' end,
      a polarity opposite to that of viral assembly. These RNA fragments (containing
      the 5' end) retain their ability to reassemble with the viral protein. This
      result is consistent with earlier evidence that the initiation site for virus
      assembly is located at the 5' end of PMV-RNA. Electron microscope examination
      suggests the presence of meta-stable size classes during the disassembly process.
      This observation might indicate a variability of the RNA-protein interactions
      along the RNA molecules.

PMID- 18635088
TI  - Viral infection of the symbiotic chlorella-like alga present in Hydra viridis.
AB  - Attempts to culture the Chlorella-like green alga found in a symbiotic
      association with the Florida strain of a green hydra, Hydra viridis, have been
      unsuccessful. Ultrastructural studies of the algae isolated from the host
      revealed that large (185 nm in diameter) viral particles appeared in the nuclear
      region of the algae 2 to 6 hr after their isolation from the hydra. By 12-20 hr,
      the entire population of algae was lysed. The source of the virus is unknown
      since it has not been detected in thin sections of intact hydra or in algal cells
      immediately after their isolation. The virus attached to the algal cell wall in a
      manner reminiscent of many bacteriophage infections. Attempts to infect three
      other culture-grown Chlorella strains with crude lysates or purified viral
      particles have been unsuccessful.

PMID- 18635089
TI  - Isolation and characterization of a virus from the intracellular green alga
      symbiotic with Hydra viridis.
AB  - The isolation and characterization of a virus (designated HVCV) from the
      symbiotic Chlorella-like green alga present in Hydra viridis (Florida strain) are
      described. The large polyhedral viral particle sedimented at ca. 2600 S in
      sucrose density gradients and had a buoyant density in CsCl of 1.295 g/ml. The
      virus contained at least 19 polypeptides (MW range, 10,300 to 82,000) and the
      major polypeptide (MW, 46,000) was a glycoprotein. The viral genome consisted of
      a double-stranded DNA with a buoyant density in CsCl of 1.7114 g/ml (52% GC) and
      a molecular weight of ca. 136 x 10(6).

PMID- 18635090
TI  - Liposome-mediated infection of plant protoplasts with tobacco mosaic virus RNA.
AB  - Tobacco mosaic virus (TMV) RNA was encapsulated in large unilamellar vesicles
      (LUV) of phosphatidylserine and was introduced into protoplasts from Vinca rosea
      suspension cultures. Infection could be effected by brief incubation of
      protoplasts with the LUV containing TMV-RNA in the presence of either
      polyethylene glycol or polyvinyl alcohol. The presence of these polymers was
      essential for infection, and postinoculation washing with the high pH-high Ca2+
      buffer enhanced infection significantly. Up to 80% of protoplasts could be
      infected under the optimal conditions as demonstrated by immunofluorescence
      technique. Calculations showed that around 2 x 10(6) TMV-RNA molecules were added
      per infected protoplast, indicating that the efficiency of infection by this
      method compares favorably with those by the existing methods for inoculating
      protoplasts from mesophyll cells with TMV-RNA. The significance of using
      protoplasts from cultured cells for infection with plant viruses and their
      nucleic acids is discussed.

PMID- 18635091
TI  - Properties of a filamentous virus of the honey bee (Apis mellifera).
AB  - An ellipsoidal particle, measuring 450 x 150 nm, from honey bees comprises a
      nucleocapsid measuring 3000 x 40 nm, containing double-stranded DNA with a
      molecular weight of approximately 12 x 10(6), which is coiled within a membrane.
      The buoyant densities in CsCl of the whole particle, nucleocapsid, DNA and DNA
      with ethidium bromide are 1.28, 1.36, 1.71 and 1.61 g/ml, respectively. The
      particle contains about 12 proteins, with molecular weights ranging from 13,000
      to 70,000, which are distributed approximately equally between the membrane and
      the nucleocapsid.

PMID- 18635092
TI  - The location of calcium ions in southern bean mosaic virus.
AB  - X-ray diffraction data were collected from crystalline southern bean mosaic virus
      soaked in EDTA at pH 5.5. Under these conditions, the virus does not swell,
      although much of the Ca2+ and Mg2+ is removed from the virions. A difference
      electron density map, at 5.0-A resolution, between this and the native data
      showed three independent peaks per icosahedral asymmetric unit. One was located
      on the quasi-threefold axis at a site where a cation would be liganded to three
      quasi-related glutamates. The other two were located on the protein-RNA interface
      related by the quasi-threefold axis, thus leaving the other related site vacant.
      Atomic absorption spectroscopy results suggest that these sites are all occupied
      by calcium ions.

PMID- 18635093
TI  - Translation of turnip rosette virus RNA in rabbit reticulocyte lysates.
AB  - Turnip rosette virus (TRosV) RNA was translated in nuclease-treated rabbit
      reticulocyte lysates, and four principal products (radioactive proteins always
      found under routine conditions) with molecular weights of 105,000, 67,000,
      35,000, and 30,000 were synthesized. Optimum conditions for translation included
      50 mM added K+, no added Mg2+, TRosV RNA at 25 to 50 mug/ml, incubation for 40 to
      60 min; these conditions gave 20-fold stimulation in the incorporation of
      [35S]methionine over endogenous background levels. The 30,000 MW protein was
      identified as virus capsid protein by peptide mapping of specific
      immunoprecipitates. Most efficient synthesis of the capsid protein was observed
      for a virus-encapsidated subgenomic RNA (denatured MW 0.5 x 10(6)). The major
      genome products of 105,000, 67,000, and 35,000 MW were shown to be related by
      peptide analysis following partial proteolysis. Time course analyses suggested
      that the 67,000 product was processed from the 105,000 product by post
      translational cleavage. The protease activity responsible for product cleavage
      was apparently viral coded and protease inhibitor studies further indicated the
      enzyme was of the thiol type. In an initiation assay using anisomycin, two
      ribosomes bound per TRosV RNA. The strategy of translation as determined for the
      virus here is discussed.

PMID- 18635094
TI  - Inhibitor of virus replication released from tobacco mosaic virus-infected
      protoplasts of a local lesion-responding tobacco cultivar.
AB  - A substance(s) inhibiting virus replication (IVR) is released into the medium
      from tobacco mosaic virus-infected protoplasts of a cultivar in which the
      infection in the intact plant is localized. IVR inhibited virus replication in
      protoplasts from both local lesion-responding resistant, Samsun NN and systemic
      responding susceptible, Samsun plants, when applied up to 18 hr after
      inoculation. It was not produced in protoplasts from susceptible plants nor from
      noninoculated protoplasts of the resistant cultivar. IVR was partially purified
      using ZnAc2 precipitation, and yielded two biologically active principles with
      molecular weights of about 26,000 and 57,000, as determined by gel filtration.

PMID- 18635095
TI  - Detection, biological effects, and transmission of a virus of the aphid
      Rhopalosiphum padi.
AB  - A virus infecting an Illinois colony of the aphid Rhopalosiphum padi (L.) was
      transmitted transovarially, and significantly decreased longevity of infected
      aphids. The virus was detected by serological assay in R. padi colonies from
      North Dakota, and in two other aphid species maintained at Illinois, R.
      rufiabdominalis (Sasaki) and Schizaphis graminum (Rondani).

PMID- 18635096
TI  - A highly basic cyanogen bromide peptide from sowbane mosaic virus protein.
AB  - The protein of sowbane mosaic virus was cleaved with cyanogen bromide (CNBr) and
      a highly basic peptide, sCB-1, was isolated by Sephadex and ion-exchange
      chromatography. The amino acid composition and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis indicated that sCB-1 had 49 amino acid
      residues. Eighteen of these residues are basic, fifteen are lysine, and three are
      arginine. sCB-1 moved faster in polyacrylamide gel electrophoresis at pH 2.2 than
      a similar sized CNBr peptide from the bean strain of southern bean mosaic virus
      with twelve basic residues. The highly basic nature of sCB-1 suggests that this
      portion of the SoMV protein sequence is involved in protein-RNA binding in the
      virus particles.

PMID- 18635097
TI  - Isolation and partial chemical characterization of a virus-like particle from a
      eukaryotic alga.
AB  - A virus-like particle (VLP) associated with the green alga Cylindrocapsa
      geminella has been purified and partially characterized. The Cylindrocapsa VLP (C
      VLP) has a polygonal profile in sectional view, ranges in diameter from 200 to
      230 nm, and has a complex, multilayered capsid. Purified VLPs, when analyzed by
      SDS-polyacrylamide gel electrophoresis, contained at least 10 proteins ranging in
      molecular weight from 10,000 to 160,000. The C-VLP contains DNA, most probably
      double-stranded, having an estimated molecular weight of 175-190 x 10(6).
      Intracellular VLPs were only observed within single-celled germlings and all
      cultures examined produced the VLP. Generally, only 4-6% of the single-celled
      germlings contained VLPs, which resulted in cell death. The physicochemical and
      biological characteristics of the C-VLP support the conclusion that the C-VLP is,
      in fact, a virus.

PMID- 18635098
TI  - Resolution and genome assignment of mRNA transcripts synthesized in vitro by
      wound tumor virus.
AB  - The 12 mRNA transcripts synthesized in vitro by purified wound tumor virus
      particles were resolved into 11 discrete species by electrophoresis on sodium
      dodecyl sulfate-polyacrylamide gels containing 7 M urea. Transcripts were
      isolated and hybridized independently to a mixture of the 12 wound tumor virus
      double-stranded genome segments. Subsequent analysis of the hybrids revealed that
      each transcript hybridized selectively to one genome segment. In this manner, the
      assignment of 10 transcripts to their corresponding genome segments was
      established. The assignment of the remaining transcripts, which hybridized to an
      unresolved mixture of genome segments 4 and 5, was determined by analyzing the
      transcription products synthesized by an exvectorial isolate of WTV that lacks
      genome segment 5.

PMID- 18635099
TI  - Vascular cell alterations and predisposed xylem infection in oats by inoculation
      with paired barley yellow dwarf viruses.
AB  - Electron microscope studies of tissue doubly infected with Sitobion avenae
      specific and Rhopalosiphum padi-specific variants of barley yellow dwarf virus
      revealed four types of alteration patterns in infected phloem cells not
      previously observed in tissue infected with either isolate alone. Cells with
      alteration patterns similar to those in tissue singly infected with either
      variant were also present. Double infections with isolates MAV (S. avenae
      specific) and RPV (R. padi-specific) predisposed the xylem to infection. This may
      be the first report of a breakdown in tissue specificity induced by double
      infection with plant viruses. Double infections with two similar isolates, 6407
      (S. avenae-specific) and 6524 (R. padi-specific), failed to predispose the xylem
      to infection. The paucity of infected cells in tissues with double infections of
      isolates MAV and RPV compared with the abundance in double infections with 6407
      and 6524, suggested interference in the plant between MAV and RPV.

PMID- 18635100
TI  - Role of the Drosophila genome in Sigma virus multiplication. I. Role of the
      ret(2)P gene; selection of host-adapted mutants at the nonpermissive allele Pp.
AB  - The allele Pp of gene ref(2)P of Drosophila melanogaster is known to inhibit the
      multiplication of certain strains of Sigma virus. From a viral strain for which
      the allele PP of ref(2)P is nonpermissive, host adapted (haP) mutants were
      selected after mutagenesis in vivo. Mutagenized virus was extracted from infected
      flies fed with 5-fluorouracil. The mutagenized virus was used to inoculate
      restrictive flies to screen haP mutants. The surviving viruses were studied in
      permissive and restrictive hosts. In a first test the capability to induce CO2
      symptom in permissive and in restrictive flies was studied for each surviving
      clone. In a second test the efficiency to initiate infection in permissive and in
      restrictive flies was compared to the wild-type efficiency for each putative
      adapted clone. From 111 surviving viruses, 23 haP mutants were thus isolated. The
      proportion of temperature-sensitive mutants was higher among haP mutants than
      among non-haP brother clones. Five ts-haP mutants appeared more temperature
      sensitive in the restrictive host than in the permissive one. In the five cases,
      the viral functions affected by the mutation were early, i.e., occurring within
      24 hr of the infection of a cell at 20 degrees and related to the replication of
      the viral genome. These results suggest that viral proteins required for early
      viral functions are implicated in the interaction with the PP allele of the
      ref(2)P host gene.

PMID- 18635101
TI  - Cucumber mosaic virus-associated RNA 5, VIII. Identification and partial
      characterization of a CARNA 5 incapable of inducing tomato necrosis.
AB  - A new satellite-like replicating RNA found in association with cucumber mosaic
      virus type 1 (CMV-1), one of the earliest CMV isolates described (Doolittle,
      1920), was identified and partially characterized. CMV-1-associated RNA 5, or
      (1)CARNA 5, was isolated from CMV-1 propagated in tomato, where it failed to
      induce lethal necrosis. In this way it was distinguished from CARNA 5 with the
      tomato necrosis-causing ability, which was redesignated (n)CARNA 5. Although
      (1)CARNA 5 and (n)CARNA 5 could be separated by 7.5% polyacrylamide gel
      electrophoresis under certain conditions, the molecules are probably identical in
      size, or nearly so. (1)CARNA 5 and (n)CARNA 5 have only limited nucleotide
      sequence homology. This is also evident from the different multitransitional
      absorbance-temperature profiles that can be obtained during the thermal
      denaturation of their respective double-stranded forms. In mixed infections in
      tomato, the replication of (1)CARNA 5 was also supported by CMV strains WT or S,
      while (n)CARNA 5 was supported by CMV-1. The biologically different (1)CARNA 5
      and (n)CARNA 5 can be considered sequence variants among a group of small
      satellite-like RNA molecules dependent upon CMV for their replication.

PMID- 18635102
TI  - Low-molecular-weight RNAs associated with tobacco ringspot virus are satellites.
AB  - The low-molecular-weight RNA associated with an isolate of tobacco ringspot virus
      [TRSV(F)] lacks polyadenylic acid [poly(A)] sequences. Complementary DNA (cDNA)
      specific to this RNA was made with an oligo(dT) primer after tailing the RNA with
      poly(A). However, a significant amount of cDNA was made only when the RNA was
      treated with alkaline phosphatase prior to tailing. Hybridization of RNA in
      solution and by a Northern blot technique showed that there was no detectable
      nucleotide sequence homology between TRSV(F) RNA and two of the low-molecular
      weight RNAs associated with this virus. These associated RNAs are therefore,
      satellites of TRSV(F). The relationship of these satellites to a previously
      reported satellite of TRSV is discussed.

PMID- 18635103
TI  - Comparative studies on tomato aspermy and cucumber mosaic viruses. VI. Partial
      compatibility of genome segments from the two viruses.
AB  - Isolated RNA genomic segments (RNAs 1, 2, and 3) of tomato aspermy virus and of
      three strains of cucumber mosaic virus (CMV) were inoculated to leaves of
      Chenopodium amaranticolor Costs and Reyn in all combinations. The data presented
      demonstrate that whereas RNA 3 is readily interchangeable between the two viruses
      to produce infections resulting in lesion development, RNAs 1 and 2 are not,
      although they are interchangeable between the three CMV strains. The possible
      significance of these observations to virus taxonomy is discussed.

PMID- 18635104
TI  - Protease activity associated with the capsule protein of Estigmene acres
      granulosis virus.
AB  - The polypeptide composition of a granulosis virus of Estigmene acrea was
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Enveloped nucleocapsids are made up of 24 polypeptides with molecular weights
      ranging from 11,000 to 98,000. Virus capsule protein contains protease activity
      which degrades capsule protein from 30,000 to 25,000 through two intermediates of
      29,000 and 27,000. The putative endoprotease is active at alkaline pH, sensitive
      to heat and diethylpyrocarbonate inhibition, and resistant to 10(-3) M
      phenylmethylsulfonyl fluoride. No alteration in the electrophoretic pattern of
      viral structural proteins was detected in virus preparations containing
      endoproteolytic activity. A low level of alkaline exoprotease activity associated
      with capsule protein was also detected.

PMID- 18635105
TI  - Cell culture studies with the IMC-Hz-1 nonoccluded virus.
AB  - Studies were conducted on an adventitious agent (Hz-1V) isolated from the IMC-Hz
      1 cell line. It appeared identical to the virus first obtained by Granados et al
      (R. R. Granados, T. Nguyen, and B. Cato, 1978, Intervirology, 10, 309-317) from a
      persistent infection of this cell line. Restriction endonuclease digestion of Hz
      1V DNA indicated the agent was different from the S nuclear polyhedrosis virus
      (HzSNPV) of the host species, Heliothis zea, from which the IMC-Hz-1 cell line
      was derived by Hink and Ignoffo (W. F. Hink and C. M. Ignoffo, 1970, Exp. Cell
      Res.60, 307-309). Hz-1V caused extensive cytopathic effects (CPE) in cultures of
      TN-368 cells and was moderately infectious to several other insect cell lines.
      The lytic nature of the infection permitted development of a plaque assay
      employing TN-368 cells. Following acute infections of TN-368 cells, persistently
      infected cultures were readily established by the surviving cells. Attempts to
      induce persistent infections of clones 10 and 13 of TN-368 were, however,
      unsuccessful. Infectious Hz-1V was shed continuously into the medium throughout
      subculturings of persistently infected cells. The infectious titer dropped
      sharply during initial subculturings, but subsequently reached a basal level at
      about the 25th passage. These cultures were resistant to superinfection by
      homologous Hz-1V, but remained as susceptible as normal TN-368 cells to
      heterologous Autographa californica M NPV (AcMNPV).

PMID- 18635106
TI  - Turnip crinkle virus RNA and its translation in rabbit reticulocyte and wheat
      embryo extracts.
AB  - Turnip crinkle virions contain genomic RNA, Mr approximately 1.4 x 10(6), small
      RNA, Mr approximately 1.5 x 10(5) and a heterogeneous collection of intermediate
      size. Turnip crinkle virion RNA was translated in rabbit reticulocyte lysates
      into three major unrelated products of molecular weight 38,000 (p38, the virion
      coat protein), 36,000 (p36), and 25,000 (p25). The same three products, but in
      different proportion, were synthesized in wheat embryo extracts. Certain
      intermediate size RNA fractions translated into p38 and p36 products much more
      efficiently than did unfractionated RNA. The 1.5 x 10(5) molecular weight RNA did
      not induce amino acid incorporation. We propose a translation map of the TCV
      genome, based on tryptic analyses of the major products and of putative read
      through proteins.

PMID- 18635107
TI  - Effect of temperature-sensitive, replication-defective mutations on RNA synthesis
      of cowpea chlorotic mottle virus.
AB  - The RNA synthesis of replication-deficient, temperature-sensitive mutants of
      cowpea chlorotic mottle virus (CCMV) with mutations on either RNA 1 or RNA 3 was
      examined in temperature shift experiments. Viral RNA synthesis by the mutants at
      25 degrees was similar to that of wild-type CCMV, but upon shift to 35 degrees ,
      synthesis of mutant virus RNAs declined over a 16-hr period in contrast to
      continued synthesis by wild-type CCMV. Continued RNA synthesis, though at a
      reduced level, by the mutants during the initial periods following the shift to
      35 degrees demonstrated that the enzymes involved in viral RNA synthesis of the
      mutants continued activity after the shift to the nonpermissive temperature.
      There was no clear correlation between a specific, defect in viral RNA synthesis
      and whether the mutation occurred on either RNA 1 or RNA 3. New replicative
      complexes appeared not to be produced at 35 degrees suggesting that gene products
      from both RNA 1 and RNA 3 may function coordinately in the replication complex.
      One mutant produced a reduced ratio of RNA 3 that was exaggerated upon shift to
      the restrictive temperature.

PMID- 18635108
TI  - A comparison of the granulosis viruses from Pieris brassicae and Pieris rapae.
AB  - The granulosis viruses of Pieris brassicae and P. rapae have been compared
      biochemically and biologically. No differences were found between virus capsules
      when examined by immunodiffusion, ELISA, or SDS-polyacrylamide gel
      electrophoresis. The virus particles were identical by immunodiffusion but
      distinguishable by ELISA. Comparison of virus particle polypeptides on SDS
      polyacrylamide gels indicated small differences in molecular weight in three of
      the polypeptides of the virus envelope but no difference between the
      nucleocapsids. There were several differences between the DNA fragments produced
      by digestion with EcoRI, BamH1, and HindIII restriction endonucleases from which
      the homology between the two DNAs was calculated to be 97.7%. The small
      structural difference between the two viruses is associated with a very large
      difference in their virulence for P. brassicae; the LD50 with P. rapae GV being
      at least 1000 times greater than with P. brassicae GV. P. rapae was much more
      susceptible to either virus than P. brassicae and in this case the LD50 values
      were not significantly different for the two viruses.

PMID- 18635110
TI  - Double-stranded ribonucleic acid from carnation cryptic virus.
AB  - The nucleic acid of carnation cryptic virus has been identified as double
      stranded RNA on the basis of (i) susceptibility to RNase in 0.1 x SSC (SSC = 0.15
      M NaCl-0.015 M sodium citrate buffer, pH 7.0) and resistance to RNase in 2 x SSC
      and to DNase, (ii) reaction with an antiserum containing antibodies to dsRNA, and
      (iii) electron microscopic appearance in nondenaturing media similar to that of
      the dsRNA of maize rough dwarf virus. Upon electrophoresis in 5% polyacrylamide
      gels carnation cryptic virus RNA separated into three major segments plus a
      fourth minor component, and had a total molecular weight of about 4 x 10(6).

PMID- 18635111
TI  - Assembly and crystallization of a T = 1 icosahedral particle from trypsinized
      southern bean mosaic virus coat protein.
AB  - The N-terminal 61 amino acid residues of the coat protein of southern bean mosaic
      virus were removed by mild trypsinolysis, resulting in a 22,000 MW fragment, P22.
      In the absence of nucleic acid, the cleaved protein could be assembled into 175 A
      diameter, T = 1, spherical particles. These particles were formed between pH 4
      and 7, at low ionic strength (I </= 0.01), and also between pH 8 and 11 when Ca2+
      ions were present. Mg2+ ions had no effect on the assembly of these spheres. The
      T = 1 particles, assembled with Ca2+ ion, were crystallized by vapor diffusion in
      ammonium sulfate at pH 9.4. The cubic crystals diffracted to at least 4 A
      resolution. The three particles in the P23 unit cell contained 222
      crystallographic symmetry.

PMID- 18635112
TI  - Purification of a host-encoded RNA-dependent RNA polymerase from cowpea mosaic
      virus-infected cowpea leaves.
AB  - A membrane-bound RNA-dependent RNA polymerase from Cowpea mosaic virus (CPMV)
      infected cowpea leaves (Vigna unguiculata) has been purified 15,000-fold by DEAE
      Sepharose CL-6B chromatography, affinity chromatography on poly(U)-Sepharose 4B,
      and glycerol gradient centrifugation. Particularly, poly(U)-Sepharose 4B
      chromatography was a very efficient purification step and, in addition, achieved
      the separation of a host-encoded terminal uridylyl transferase activity from the
      RNA polymerase activity. On glycerol gradient centrifugation, the polymerase
      activity sedimented as a homogeneous peak with a rate corresponding to a
      molecular weight of 120,000. Analysis of the protein composition of the gradient
      fractions revealed that only one polypeptide with a molecular weight of 130,000
      cosedimented with the polymerase activity, suggesting a monomeric enzyme. The
      most purified enzyme preparations from CPMV infected leaves did not contain
      polypeptides encoded by RNA from CPMV B-component which presumably carries
      functions essential for CPMV replication. Using the same purification procedure,
      an RNA-dependent RNA polymerase has also been purified from mock-inoculated
      leaves, which appeared to be identical to the RNA polymerase from infected
      leaves. This host enzyme was strongly stimulated in cowpea leaves infected with
      CPMV. The role, if any, of the RNA-dependent RNA polymerase from cowpea leaves in
      CPMV-RNA replication is discussed in view of the recent evidence for virus
      encoded functions involved in CPMV multiplication.

PMID- 18635113
TI  - A comparative study of the cowpea and bean strains of southern bean mosaic virus.
AB  - Features of the primary structure and translation of the genomic RNAs of the
      cowpea and bean strains of southern bean mosaic virus have been investigated in
      order to assess the similarity of the two viruses. The sequence of 400 bases at
      their 3' termini have been determined. These include the 3' noncoding regions and
      extend well into the coat protein cistrons. The noncoding regions (136 bases for
      the cowpea strain RNA and 129 bases for the bean strain RNA) show no obvious
      sequence homology. However, extensive base as well as amino acid sequence
      homology exists in the coding region. RNAs from both strains have a small protein
      attached to their 5' terminus-the protein in the cowpea strain being the smaller
      of the two. In vitro studies show that there are similarities in the overall mode
      of translation of the genomes of the two viruses. Although corresponding proteins
      are synthesized they differ in size.

PMID- 18635114
TI  - Comparative studies on tomato aspermy and cucumber mosaic viruses. VII.
      Serological relationships reinvestigated.
AB  - Distant antigenic relationships between Australian strains of tomato aspermy
      virus (TAV) and cucumber mosaic virus (CMV) were investigated by three
      serological methods: radial double immunodiffusion in agar, enzyme-linked
      immunosorbent assays (ELISA), and immune-electron microscopy (IEM) using the
      antibody decoration technique. Based on the work with TAV and CMV presented in
      this paper, it appears that the ELISA method is especially suitable for studying
      antigenic relationships among viruses. For distinguishing closely related
      viruses, heterologous antibodies were used for both coating the ELISA plates and
      for conjugating with enzyme. On the other hand, for establishing distant
      antigenic relationships, heterologous and homologous antibodies were used for
      coating and coupling to enzyme, respectively. Immunodiffusion tests were less
      efficient than ELISA in distinguishing minor antigenic differences between
      strains of CMV and also, and distant relationship between TAV and CMV was not as
      clearly detected. Decoration of the virus particles with antibodies in IEM was
      the least satisfactory method for investigating antigenic relationships among the
      viruses.

PMID- 18635115
TI  - No viral gene is able to elicit RNA-dependent RNA polymerase in cucumber mosaic
      virus-infected cucumber cotyledons.
AB  - Infection of cucumber cotyledons by cucumber mosaic virus, a divided genome
      virus, leads to the early appearance of considerable RNA-dependent RNA polymerase
      activity. When the genome components were tested separately for this effect, no
      single one was found active, and different combinations of two components caused
      varying lesser stimulations than when the three components necessary for
      infectivity were used. These intermediate effects paralleled the infectivities of
      these two-component mixtures. It appears probable that the stimulation of enzyme
      production is the consequence of viral infection, rather than being attributable
      to one or more viral genes.

PMID- 18635117
TI  - Evidence for a 58-kilodalton polypeptide as precursor of the coat protein of
      cauliflower mosaic virus.
AB  - Purified cauliflower mosaic virus subjected to agarose gel electrophoresis
      separated into two zones, slow and fast, with the latter consisting of less than
      5-10% of the total. When these two types of virions were excised from gels and
      subjected to analysis in dodecyl sulfate impregnated gels, the fast component
      consisted mainly of the 58- and 44-kilodalton (kd) phosphorylated forms of the
      coat protein whereas the slow component contained only lower molecular weight
      forms of the same protein. Pulse labeling experiments with 32P (as
      orthophosphate) or tritiated thymidine showed the fast electrophoretic form of
      the virus to become labeled more rapidly than the slow form. With long labeling
      periods the slow form accumulated more label than the fast form suggesting a
      precursor-product relationship between the fast and slow electrophoretic forms.
      With [32P]orthophosphate or [35S]methionine labeling, the 58-kd phosphorylated
      protein showed a much higher relative level of labeling than that obtained with
      protein stains such as Coomassie blue. With longer labeling periods greater
      amounts of activity appeared in the 44-kd and lower molecular weight forms of the
      coat protein. These results supported previous results suggesting that the 58-kd
      protein is the primary translation product of the coat protein gene and that this
      is the form used in encapsidation to produce mature virions.

PMID- 18635118
TI  - Structure and 5'-termini of the large and 19 S RNA transcripts encoded by the
      cauliflower mosaic virus genome.
AB  - Cauliflower mosaic virus-infected leaves accumulate two major RNA species late in
      infection-a 19 S RNA and a large RNA transcript. We have found that the large
      transcript is approximately full genome length. The 3'-end of the large
      transcript is located at or near a site corresponding to the 3'-end of the 19 S
      RNA. The 5'-end of the large transcript maps near its own 3'-end and only about
      100 bp downstream from the terminator codon for coding region VI. The 5'-end of
      the large transcript is situated at the beginning of the large intergenic region,
      about 600 bp upstream from the single-strand break in the transcribed viral DNA
      strand. The location of this site is of particular interest because it suggests
      that synthesis of the large transcript proceeds across the DNA break site. The 5'
      end of the 19 S RNA maps in the small intergenic region between coding regions V
      and VI about 20-30 bp upstream from the initiation codon for coding region VI. By
      comparing the transcription initiation sites to DNA sequences for the CaMV
      genome, it can be shown that TATATAA sequences lie 20-30 bp upstream from the 5'
      ends of both the 19 S and large transcripts.

PMID- 18635119
TI  - Genotypic variation among wild isolates of Heliothis spp nuclear polyhedrosis
      viruses from different geographical regions.
AB  - Ten nuclear polyhedrosis viruses infecting insect hosts in the genus Heliothis
      and isolated in different geographical regions of the world were characterized
      using restriction endonuclease analysis. Digestion of the dsDNA genomes with
      BamHI, EcoRI, and HindIII resulted in fragmentation profiles which separated the
      wild-type isolates into two major genotypes, corresponding with the morphology of
      the virion (multiply embedded major genotypes, corresponding with the morphology
      of the virion (multiply embedded vs singly embedded). Isolates within each major
      genotype have similar fragmentation profiles, showing only slight differences in
      the number and size of several fragments, and thus represent variants of the
      major genotype. Submolar fragments present in a number of the digests suggests
      that these wild-type isolates might themselves consist of two or more genotypic
      variants. The significance of this genotypic heterogeneity is discussed.

PMID- 18635120
TI  - Evidence that RNA 4 of alfalfa mosaic virus does not replicate autonomously.
AB  - A mutant (Tbts7) of alfalfa mosaic virus, the coat protein of which is unable to
      activate the viral genome (the RNA species 1, 2, and 3, which need some coat
      protein for infectivity) at 30 degrees , can be rescued at this temperature by
      adding to the inoculum wild-type RNA 3 (the genome part that contains the coat
      protein cistron), but not adding wild-type RNA 4 (the subgenomic messenger for
      the coat protein). Unless RNA 3 of Tbts 7 has a second ts mutation at a site not
      occurring in RNA 4, it may be concluded from the above finding that RNA 4 does
      not replicate autonomously.

PMID- 18635121
TI  - Free cauliflower mosaic virus supercoiled DNA in infected plants.
AB  - Evidence is presented indicating that free viral DNA exists in Cauliflower mosaic
      virus-infected leaves. Among the different viral DNA forms detected in total DNA
      extracts is a supercoiled form. We discuss its possible role in the replication
      process.

PMID- 18635122
TI  - The isolation and characterization of the MP and FP plaque variants of Galleria
      mellonella nuclear polyhedrosis virus.
AB  - Two plaque morphologies were detected in assays of Galleria mellonella nuclear
      polyhedrosis virus preparations which had been serially passaged in the TN-368
      cell line. The FP (few polyhedra) plaques were larger (0.7-mm average diameter)
      and the infected cells contained less than 10 polyhedra each. The MP (many
      polyhedra) plaques were smaller (0.5-mm average diameter), and the infected cells
      contained greater than 10 each. Only the FP variant could be purified by plaque
      picking and remained pure through 10 serial injection passages in last-instar
      Galleria mellonella larvae, while the MP variant always produced FP plaques after
      serial passage in cell cultures or by injection of larvae. Bioassays of MP and FP
      polyhedra demonstrated a 350-fold reduction in virulence for FP polyhedra.
      Electron micrographs of these polyhedra showed that both variants were MNPV type
      viruses, although the FP polyhedra were predominantly devoid of nucleocapsids.
      Electron microscopic observations of MP- and FP-infected cell cultures revealed
      an apparent deficiency in de novo membrane synthesis in FP infections. SDS
      polyacrylamide gel electrophoresis of cell-released nonoccluded virus proteins
      demonstrated several differences in protein composition between the two variants.
      The evidence indicates that the FP variant of G. mellonella nuclear polyhedrosis
      virus is a stable genotypic variant which arises from spontaneous mutation of the
      MP variant.

PMID- 18635123
TI  - Electron microscopy of double-stranded nucleic acids found in tissue infected
      with the satellite of tobacco ringspot virus.
AB  - Electron microscopic studies of the ds RNAs purified from plants infected with
      the satellite (S) of tobacco ringspot virus (TobRSV) revealed that approximately
      91% of the population is linear, varying in length between 40 and 3000 nm. Six
      percent of the population appeared as relaxed circles, and the balance appeared
      as "racket"-like structures. Electrophoretic analysis of these preparations
      detected at least 12 components higher in molecular weight than the expected
      230,000-dalton RF. Denaturation of the same sample released ss RNA that
      coelectrophoresed with STobRSV RNA from virions. The linear ds molecules,
      although extremely variable in length, have some preferential distribution around
      130 nm, not around 68 nm, the length of ss STobRSV RNA; the circles also varied,
      but their lengths fell into four distinct peaks: the shortest was 130 nm, and the
      increment of each longer circle was also about 130 nm. The circular portion of
      the "racket"-like structure was a uniform 130 nm, with a varied linear portion.
      However, the most frequent linear dimension was also 130 nm. Denatured ds RNA
      varied in length, and most molecules fell in between 50 and 185 nm. Relaxed
      circles and "racket"-like structures were also present, but much less frequently
      than in the undenatured preparation. T1 RNase degradation of ds StobRSV RNA made
      the linear population more uniform in length (between 60 and 130 nm), most
      preferentially around 130 nm, and decreased the number of circles and "racket"
      like molecules.

PMID- 18635124
TI  - A temperature-sensitive strain of tobacco mosaic virus defective in cell-to-cell
      movement generates an altered viral-coded protein.
AB  - An analysis has been made of the proteins synthesized in vivo and in vitro from
      two closely related tomato strains of tobacco mosaic virus, one of which is
      defective in cell-to-cell movement at a restrictive temperature [Nishiguchi et
      al. (1978). J. Gen. Virol. 39, 53-61]. The coat proteins of the two strains (L,
      and the temperature-sensitive LS-1) are identical as revealed by two-dimensional
      tryptic peptide maps prepared from proteins synthesized in vivo. Peptide maps of
      the 30,000, 130,000, and 165,000 Mr viral RNA in vitro translational products
      revealed a slight difference only in the 30,000 Mr polypeptides of the two
      strains, implicating this polypeptide as a factor mediating cell-to-cell movement
      of virus in the leaf.

PMID- 18635125
TI  - Carbon-13 NMR study of southern bean mosaic virus.
AB  - The motional state of the coat protein of southern bean mosaic virus (SBMV)
      particles has been studied by 13C NMR at 50.3 MHz. In the native virus, 13C-NMR
      signals are observed only from a few highly mobile amino acid side chain groups
      such as methyls or from unprotonated carbons such as carbonyls or arginine-zeta.
      After swelling SBMV by treating with EDTA, additional 13C-NMR peaks become
      visible. The pattern of resonances matches that expected from the side chains of
      those amino acid residues identified to be on the surface of the virus particle
      based on the known crystal structure. After further disruption of the virus
      structure by 0.5 M KCl, the 13C-NMR peaks sharpen, and additional peaks appear,
      but the set of peaks appears to correspond only to surface amino acid side
      chains.

PMID- 18635126
TI  - Intermediates of the in vitro assembly and disassembly of southern bean mosaic
      virus.
AB  - Southern bean mosaic virus (SBMV) was swollen by treatment with EDTA at pH 7.5
      and dissociated into RNA and protein in 1 M NaCl. Aliquots of this preparation
      were diluted with appropriate buffers to obtain samples in varying concentrations
      of NaCl, and components of these samples were sedimented through sucrose
      solutions and dissolved in 0.01 M Tris-HCI buffer, pH 7.5. The protein content
      and sedimentation properties of components in these preparations were determined.
      When the NaCl molarity in the treatment exceeded 0.6 M the preparations contained
      RNA with approximately six protein subunits per SBMV RNA molecule. The protein
      content of the preparations increased from 30 protein subunits per RNA molecule
      to 145 protein subunits per RNA molecule as the NaCl molarity used in the
      treatment was decreased from 0.5 to 0.1 M. The positions of sedimentation of
      components in these preparations in density gradient centrifugation were
      intermediate between those of RNA and EDTA-swollen virus. The sedimentation rate
      of these assembled components increased as the NaCl molarity used in the
      treatment was decreased. Similar components were assembled when preparations of
      RNA and protein dissociated from SBMV by dialysis in neutral buffers containing
      EDTA and 1 M NaCl were diluted to lower NaCl molarities. When SBMV was swollen by
      treatment with EDTA and dissociated in various concentrations of NaCl, the
      components formed were similar to those obtained by assembly in the same NaCl
      molarities. Preparations in the pH 7.5 buffer contained single components which
      sedimented at 56 S, 55 S, 54 S, 51 S, 46 S, 38 S, 33 S, and 24 S. With the
      exception of the 24 S component, components formed by disassembly in the same
      NaCl molarities and dissolved in pH 5.0 buffer sedimented faster.

PMID- 18635127
TI  - Purification and characterization of hop stunt viroid.
AB  - The hop stunt viroid (HSV) has been purified from cucumber leaves infected with
      the hop stunt disease agent. Electron microscopic observation of denatured HSV
      shows a typical viroid RNA molecule of covalently closed circular form. The
      molecular length was estimated to be 290-300 nucleotides by electron microscopic
      measurement and polyacrylamide gel electrophoresis using potato spindle tuber
      viroid as a standard. HSV is one of the smallest viroids characterized so far.
      HSV preparations were separated into covalently closed circular and linear forms
      by polyacrylamide gel electrophoresis under fully denaturing conditions. Both
      circular and linear molecules were found to be infectious.

PMID- 18635128
TI  - Molecular cloning of the complementary DNA copies of the common and cowpea
      strains of tobacco mosaic virus RNA.
AB  - Complementary DNA (cDNA) copies of the common (OM) and Cowpea (Cc) strains of
      tobacco mosaic virus (TMV) RNA polyadenylated in vitro have been synthesized with
      AMV reverse transcriptase and oligo (dT)10 as primer. The cDNA was converted to a
      double-stranded form by E. coli DNA polymerase I followed by S1 nuclease
      digestion. The double-stranded cDNA copies were cloned in pBR322 at the PstI site
      using the oligo(dC)-oligo(dG) tailing method. With the common strain, several
      clones containing inserts covering different parts of genomic RNA were selected
      using partially reconstituted RNA and partially stripped virus RNA as
      hybridization probes. Restriction mapping of three clones and their overlaps
      showed that cloned sequences covered about 4000 nucleotides of the common strain
      RNA from the 3' end. With the Cc strain, clones containing the 3' portion were
      selected by Southern hybridization using coat protein mRNA isolated from short
      particles as a probe. One cloned recombinant plasmid was found by restriction
      analysis and R-loop mapping to carry about a 1700 nucleotide sequence of Cc
      strain RNA from the 3' end. A restriction map of the OM strain was very similar
      to the map of the vulgare strain, as predicted from its nucleotide sequence, but
      completely different from that of Cc strain.

PMID- 18635129
TI  - Ultrastructure of turnip crinkle- and saguaro cactus virus-infected tissues.
AB  - An electron microscope study of different hosts infected with turnip crinkle
      (TCV) and saguaro cactus (SCV) viruses, two tentative members of the tombusvirus
      group, was carried out. Particles of both viruses were readily detected in cells
      of different tissues, in the cytoplasm of which they occurred in great numbers,
      though not in crystalline arrays. Cytological modifications of various types were
      also observed. The most striking of these was an extensive peripheral
      vesiculation of mitochondria in TCV-infected cells, which was accompanied by
      plastic activity of the organelles that often engulfed portions of ground
      cytoplasm and virus particles. Cytoplasmic inclusion bodies were not present.
      Likewise, none of the cytopathological features characterizing tombusvirus
      infections was observed. No indications were obtained to support the idea that
      TCV and SCV may continue to be considered members, even though tentative, of the
      tombusvirus group.

PMID- 18635130
TI  - In vitro translation products of turnip crinkle virus RNA.
AB  - Turnip leaves infected with turnip crinkle virus accumulate a 35-kd polypeptide
      which comigrates with the major protein from isolated virions. RNA from TCV
      virions directs the synthesis of a number of polypeptides in vitro including a 35
      kd protein which is immunoprecipitable with antiserum to virus particles.
      Translation of viral RNA size-fractionated on sucrose gradients or methyl
      mercurichydroxide-containing gels shows that the TCV coat protein is synthesized
      primarily from RNA fragments which are smaller than the genomic RNA. A satellite
      RNA species found in virions does not direct the synthesis in vitro of any
      identifiable protein.

PMID- 18635131
TI  - Cross-protection and interference between electrophoretically distinct strains of
      cucumber mosaic virus in tomato.
AB  - Cucumber mosaic virus (CMV) was partially purified by polyethylene glycol
      precipitation from extracts of tomato leaflets. The presence and quantity of two
      strains with different electrophoretic mobilities was analyzed by polyacrylamide
      gel (2.5%) electrophoresis of preparations from as little as 50 mg of tissue.
      This method was used to analyze interference and cross-protection between the
      strains. Coinoculation resulted in local and systemic mixed infections and
      reductions in the synthesis of both strains. Systemic symptoms and accumulation
      of the strain with the more severe symptoms were not detected in up to 13 newly
      formed leaves in five of six plants preinfected with the mild strain and
      challenged with the severe strain. Systemic accumulation of the mild strain was
      not detected in each of six plants preinfected with the severe strain and
      challenged with the mild strain. Both strains could accumulate in challenge
      inoculated leaves. The level or absence of interference in these leaves did not
      affect systemic cross-protection. Cross-protection between these strains of CMV
      involves considerable inhibition of virus accumulation in addition to absence of
      symptoms.

PMID- 18635132
TI  - The structure of an unusual ordered aggregate of papaya mosaic virus protein.
AB  - The structure of unusual rod-shaped particles made from papaya mosaic virus
      protein in methylpentanediol is described. It is shown how the structural
      subunits group to form the morphological subunits observed on the particles.

PMID- 18635133
TI  - Does tobacco mosaic virus RNA contain cytokinins?
AB  - Tobacco mosaic virus was previously reported to contain between 5 and 17 modified
      nucleosides with cytokinin activity per RNA molecule. Using a new and highly
      sensitive method for gas chromatography of permethylated cytokinins, we were
      unable to detect cytokinins in enzymic or alkaline digests of TMV RNA. The method
      was sensitive enough to assay 1 cytokinin nucleoside per 10 TMV RNA molecules.
      Soybean callus bioassay also failed to detect activity in TMV RNA hydrolysates
      which corresponded to any of the cytokinin nucleosides known to occur in RNA. We
      therefore suggest that TMV RNA does not contain cytokinin nucleosides.

PMID- 18635134
TI  - A study of TMV ts mutant Ni2519. I. Complementation experiments.
AB  - Two distinct virus-specific functions, i.e., virus assembly and spreading of
      infection from cell to cell (transport function), are temperature-sensitive (ts)
      in TMV mutant Ni2519. Assembly of Ni2519 cannot be complemented by the
      temperature-resistant TMV strains used: A14 (a wild type strain from which Ni2519
      was derived) and dolichos enation mosaic virus (DEMV, or cowpea strain of TMV), a
      thermophilic strain. On the other hand, Ni2519 can serve as a donor of the coat
      protein to complement is strain Ni118, which has a mutation in the coat protein
      gene. The genomic RNA can be produced by Ni2519 at a nonpermissive temperature;
      functionally active Ni2519 coat protein (capable of coating Ni118 RNA upon mixed
      infection) is produced at a nonpermissive temperature as well. The is phenotype
      of Ni2519 upon virus assembly probably results not from the ts behavior of any
      virus-coded protein(s) but is due to the ts properties of the genomic RNA
      molecule itself, so the possibility of the complementation of assembly of Ni2519
      is ruled out. Thus, Ni2519 appears to represent a novel class of virus mutants
      with is virion RNA. The second is function of Ni2519 (transport of infection) can
      be complemented by a helper virus. The experimental system used for
      complementation of the transport function allowed Ni2519 to spread from cell to
      cell at a nonpermissive temperature. Obviously, Ni2519 infection spreads under
      these conditions in a form different from that in the mature virions, since its
      assembly cannot be complemented by the helper virus. Some aspects of the
      transport function are discussed.

PMID- 18635135
TI  - A study of TMV ts mutant Ni2519. II. Temperature-sensitive behavior of Ni2519 RNA
      upon reassembly.
AB  - The virion RNA of the temperature-sensitive (ts) TMV mutant Ni2519 was used in
      experiments on in vitro reconstitution. At 24 degrees RNA of Ni2519 can be
      reassembled into an infective virus. At 33 degrees the reassembly of Ni2519 RNA
      results in defective (ribonuclease sensitive) virus particle (DVP) formation. The
      site of the Ni2519 RNA molecule available for RNase attack is located at a
      distance of about 600-800 nucleotide residues from the 3'-end in DVP assembled at
      33 degrees . It has been shown that it is the initiation (rather than elongation)
      phase of the virus reconstitution that is temperature-sensitive. The results of
      an electron microscopic analysis suggest that at least two reconstitution
      initiation sites (RIS) are operative upon Ni2519 RNA assembly at a nonpermissive
      temperature (33 degrees). On the contrary, a single RIS is observed in Ni2519 RNA
      at 24 degrees and in TMV vulgare RNA at 33 degrees. It is suggested that the
      process of reassembly starts from two initiation sites at 33 degrees and results
      in the defective particle formation. A model of TMV Ni2519 DVP reassembly at
      restrictive temperature is offered.

PMID- 18635136
TI  - A study of TMV ts mutant Ni2519. III. Location of the reconstitution initiation
      sites on Ni2519 RNA.
AB  - It was suggested in an accompanying paper [Taliansky et al. (1982b), Virology,
      117, 000-000] that two reconstitution initiation sites (RIS I and RIS II) were
      functionally active in RNA of the temperature-sensitive (ts) TMV mutant Ni2519
      upon reassembly at a nonpermissive temperature; initiation of reassembly that
      started at two sites on the Ni2519 RNA molecule resulted in defective
      (ribonuclease-sensitive) virus particle (DVP) formation. RIS(s) was(were) defined
      as a segment(s) of Ni2519 RNA protected from the action of ribonuclease T1 by the
      coat protein within an incomplete nucleoprotein complex (I-NPC) formed upon
      limited TMV reassembly at nonpermissive (33 degrees and permissive (24 degrees)
      temperatures. Tl-resistant oligonucleotides protected within I-NPC were finger
      printed, sequenced, and assigned to specific regions on the Ni2519 RNA molecule.
      It was shown that only RIS I was operative on Ni2519 RNA at 24 degrees as well as
      on A14 (a temperature-resistant strain, the wild type for Ni2519) RNA at both 24
      and 33 degrees ; RIS I corresponded to the so-called Oa (origin of assembly) of a
      common TMV strain previously studied and was located at a distance of about 800
      nucleotides from the 3'-end of the RNA molecule. In contrast, two RISs were
      revealed on Ni2519 RNA assembled at 33 degrees ; of the two RISs operative in
      this case the first one is identified as RIS I, while the second (RIS II) is
      located within 300-520 nucleotides from the 3'-end, i.e., within the coat protein
      gene. The latter corresponds to the so-called SERF (specifically encapsidated RNA
      fragment) of the RNA of common TMV.

PMID- 18635137
TI  - Double-stranded viral RNA content in tobacco leaves infected with virulent-and
      avirulent isolates of tomato mosaic virus.
AB  - The changes in double-stranded RNA content in tobacco leaves inoculated with
      tomato mosaic virus (ToMV) and its avirulent mutant N14 were compared by
      [3H]uridine incorporation and resistance to RNase. It was found that the content
      of double-stranded RNA (dsRNA) in leaves infected with N14 was higher than in
      those infected with ToMV. At the second day after inoculation, the percentage of
      dsRNA resistant to RNase in leaves inoculated with N14 was 58.4%; in those with
      ToMV it was 42.8%. Subsequently the ToMV-dsRNA rapidly declined to 10.4-18.5%,
      but N14-dsRNA remained at higher levels, from 25.5 to 36.6%. The possible role
      that a higher content of dsRNA might play in expressing virulence of single
      stranded RNA viruses is discussed.

PMID- 18635138
TI  - Subgenomic components of tobacco rattle virus in infected tissue.
AB  - Cells infected with the CAM strain of tobacco rattle virus (TRV) contain at least
      five species of virus-specific RNA in addition to the two genomic RNAs. These
      species were detected by hybridizing [(32)P]cDNA prepared to TRV RNAs-1 and -2
      with electrophoretically separated infected cell RNA species immobilized on
      diazotized paper. The new viral RNA species have the following apparent molecular
      weights: RNA-3, 0.5 x 10(6); RNA-4, 0.22 x 10(6); RNA-5, 1.1 X 10(6); RNA-6,0.36
      x 10(6); RNA-7, 0.16 x 10(6). RNA-5 is generated from RNA-1 since it hybridizes
      with RNA-1 cDNA but not with cDNA prepared to RNA-2. The rest hybridize with RNA
      2 cDNA and thus are generated from the smaller genomic species.

PMID- 18635139
TI  - A neutron scattering study of the structure of compact and swollen forms of
      southern bean mosaic virus.
AB  - Neutron small-angle scattering in H2O/D20 buffers has been used to investigate
      the radial distribution of protein and RNA in the compact and swollen forms of
      southern bean mosaic virus (SBMV). The architecture of the particle is described
      by a set of four concentric shells. Compact SBMV was found to consist of a
      tightly packed outer protein shell, with the RNA and about 15% of the protein at
      the interior of the particle. The protein penetrates as deeply as the RNA toward
      the center. This structure resembles that of tomato bushy stunt virus although
      the average distribution of the protein is much less bilobal. There is no major
      reorganisation of the architecture of the virion upon swelling induced by the
      removal of divalent ions at pH 8.5: the radii of all four shells increase by
      about 15 A, with a concomittant decrease of the packing density. Possible
      correlations between the mechanism of swelling and the architecture and stability
      of small isometric virions are discussed.

PMID- 18635140
TI  - Structure of the 3' extremity of barley stripe mosaic virus RNA: evidence for
      internal poly(A) and a 3'-terminal tRNA-like structure.
AB  - The results of a previous study suggested that the poly(A) sequence in barley
      stripe mosaic virus (BSMV) RNA is intercalated between a 3'-terminal tyrosine
      accepting structure and the 5'-terminal coding part of the BSMV genome. Here we
      show that poly(A)+ and poly(A)- fractions of BSMV RNA can be cleaved into two
      fragments specifically at the position of poly(A) or oligo(A) sequence with RNase
      H from Escherichia coli in the presence of oligo(dT)10. The shorter fragment (Sh)
      retains the ability of intact viral RNA to be aminoacylated, i.e., it represents
      the 3'-terminal part of BSMV RNA. Electrophoretic analysis of Sh-RNA reveals
      three closely positioned subspecies with an average length of about 210
      nucleotides. The long 5'-terminal RNA fragment (L) produced by RNase H treatment
      has electrophoretic mobility similar to that of intact BSMV RNA, but displays
      neither amino acid-accepting ability nor infectivity. Nevertheless, L-RNA
      possesses the same messenger activity as the intact viral RNA and codes for the
      same pattern of polypeptides in rabbit reticulocyte lysate in vitro translation
      assays.

PMID- 18635141
TI  - Amino acid sequence of southern bean mosaic virus coat protein and its relation
      to the three-dimensional structure of the virus.
AB  - The amino acid sequence of the coat protein of southern bean mosaic virus has
      been determined. Chemical techniques were supplemented by a 2.8-A-resolution
      electron-density map which helped in assigning absolute positions for each
      peptide. Four amino acids and the placement of one heptapeptide near the amino
      terminus of the protein were interpolated by comparison with the partially known
      southern bean mosaic virus RNA sequence. The subunit is heavily lined with basic
      residues on the side facing the RNA. Subunit-subunit interactions are hydrophobic
      and ionic. The calcium site on the quasi-threefold axis has three glutamic
      residues as ligands. There is a disulfide bond, between Cys 168 and 176, within a
      sequence which is inserted in southern bean mosaic virus relative to the tomato
      bushy stunt virus structure. This portion is a helix nestling between the "beta
      barrel" subunit structure and the RNA interior.

PMID- 18635142
TI  - The specific involvement of coat protein in tobacco mosaic virus cross
      protection.
AB  - Nicotiana sylvestris infected by strains of tobacco mosaic virus (TMV) causing
      mosaic can be superinfected in the dark green leaf tissue, but not light green
      tissue, by necrotizing strains of TMV. The dark green tissue, however, is much
      less susceptible than healthy tissue, to some extent, even to unrelated viruses.
      The RNA of necrotizing strains of TMV was relatively more infectious than intact
      virus on mosaic than on healthy leaves and caused lesions in both light and dark
      green tissues. The same relationship was found in Nicotiana longiflora and, when
      the protecting strain in N. sylvestris could be used as a challenge, in Capsicum
      baccatum. The efficiency of superinfection by RNA was not found with viruses
      unrelated to TMV. When bentonite at 1 mg/ml, which is known to strip protein from
      TMV, was included in the inoculum of intact TMV it superinfected in the same
      manner as RNA. RNA of a necrotizing strain of TMV, encapsidated in brome mosaic
      virus protein and used as a challenge, superinfected in the same manner as RNA.
      When encapsidated in common TMV protein, however, it behaved as native virus.
      Cross protection apparently results from the prevention of uncoating of related
      challenge virus in light green tissue of N. sylvestris. Locally inoculated N.
      sylvestris leaves were insusceptible to challenge RNA or intact virus when the
      protecting virus was increasing. After increase ceased, RNA was more infectious
      than intact virus.

PMID- 18635143
TI  - Analysis of the in vitro coding properties of the 3' region of turnip yellow
      mosaic virus genomic RNA.
AB  - The genomic RNA of turnip yellow mosaic virus (TYMV) codes in vitro for two
      proteins of 195,000 (195K) and 150,000 (150K) daltons initiated at the same site
      of the RNA. In the presence of yeast amber suppressor tRNA, synthesis of the 195K
      protein is reduced in favor of a 210,000-dalton (210K) protein. Using TYMV RNA
      sequence data and comparison of tryptic peptides of the 150K, 195K, 210K, and
      coat proteins, we postulate that the silent region between the 195K gene and the
      coat protein gene located in the 3' region of TYMV genomic RNA is only 14
      nucleotides long.

PMID- 18635144
TI  - Characterization of DNA from a granulosis virus of Estigmene acrea:
      (Lepidoptera).
AB  - A granulosis virus was isolated from Estigmene acrea larvae by sucrose density
      gradient centrifugation. The viral DNA is circular with a molecular weight
      calculated from contour length measurements of 73 x 10(6). Digestion of E. acrea
      granulosis virus DNA with restriction endonucleases HindIII and BamHI gave an
      average genome molecular weight of 72 x 10(6) and revealed a DNA cleavage pattern
      different from those of other granulosis viruses of identical genome size.

PMID- 18635145
TI  - Mechanism for release of RNA from turnip yellow mosaic virus at high pH.
AB  - The formation of empty protein shells from intact turnip yellow mosaic virus
      (TYMV) following treatment at alkaline pH has been investigated. The loss of
      viral RNA is accompanied by the release of a small amount of protein which has
      sedimentation properties expected for aggregates of about five to eight coat
      protein subunits. These results imply that the release of RNA at elevated pH
      occurs concomitantly with the removal of a discrete amount of protein from the
      virus shell. The protein released may be associated with the viral RNA since its
      sedimentation properties are altered following treatment with pancreatic
      ribonuclease.

PMID- 18635146
TI  - DNA restriction-pattern differences from geographic isolates of Spodoptera
      littoralis nuclear polyhedrosis virus.
AB  - Two nuclear polyhedrosis viruses were isolated from Spodoptera littoralis larvae
      collected from several areas in Israel. The two viruses were characterized and
      compared by restriction endonuclease cleavage of their DNA and Southern blot
      hybridization. The two viruses have no detectable sequence homology. A variant,
      homologous to the more common virus isolate, was also found.

PMID- 18635147
TI  - Alteration of Autographa californica nuclear polyhedrosis virus DNA upon serial
      passage in cell culture.
AB  - Plaque-purified Autographa californica nuclear polyhedrosis virus, AcMNPV E2
      isolate, was propagated for 30 generations by serial passage in TN-368 cells.
      After passage, the DNAs from 7 of 20 replaque-purified isolates were found to
      have additional EcoRI restriction enzyme fragments. These 7 isolates were of
      three types. The additional EcoRI fragments of each isolate hybridized to
      existing viral DNA. Restriction enzyme mapping with SacI and SmaI show that
      isolates of each type contain an insertion of repeated viral DNA in approximately
      the same region of the genome. The origin and location of this DNA is discussed.

PMID- 18635148
TI  - Inhibition of Autographa californica nuclear polyhedrosis virus replication in
      high-density Trichoplusia ni cell cultures.
AB  - Replication of the Autographa californica nuclear polyhedrosis virus was studied
      in Trichoplusia ni (TN-368) tissue culture cells under cell density conditions
      which approximated a confluent monolayer (5.7 x 10(5) cells/cm(2) growth
      surface). These high-density cultures were not refractory to infection but the
      synthesis of both the occluded and nonoccluded forms of the virus were inhibited
      greater than 98% when compared to inoculation of low cell density cultures (1.4 x
      10(5) cells/cm(2)). The inhibition phenomenon was not due to depletion of a
      medium component or a diffusable cell-associated factor. The inhibition was
      reversible and required cell-to-cell contact. Viral-induced protein synthesis
      studies using 35S-labeled methionine incorporation indicated an 18-hr delay in
      the synthesis of one of the four early proteins under high cell density
      conditions. DNA:DNA dot hybridization and 3H-labeled thymidine incorporation
      studies indicated that cell-to-cell contact reversibly inhibited both cellular
      and viral DNA synthesis.

PMID- 18635149
TI  - Use of dodecyl-beta-D-maltoside in the purification and stabilization of RNA
      polymerase from brome mosaic virus-infected barley.
AB  - The activity and specificity of RNA-dependent RNA polymerase (replicase) isolated
      from brome mosaic virus-infected barley was enhanced by extraction with the
      nonionic detergent dodecyl-beta-d-maltoside. The enzyme was stable for at least 8
      weeks when stored at -70 degrees . A further 100-fold purification was obtained
      by centrifugation through sucrose in the presence of detergent. The polymerase
      activity was associated with the pellet fraction; the template dependence and
      specificity were similar to those of the enzyme before sucrose purification. SDS
      PAGE analysis revealed a 110-kd protein in the purified pellet fraction from
      infected leaves that was absent from a similar fraction from healthy leaves. The
      protein had an identical electrophoretic mobility to that of protein la, the
      product of brome mosaic virus RNA 1 translation in vitro, and the profile of its
      tryptic polypeptides was very similar to that of protein 1a. These results
      support data obtained by inoculation of protoplasts with separated BMV RNA
      components (Kiberstis, et al. (1981), Virology 112, 804-808) that are consistent
      with the notion that RNA 1 codes for the viral replicase, or a subunit thereof.

PMID- 18635150
TI  - The primary structure of cowpea chlorotic mottle virus coat protein.
AB  - The amino acid sequence of the coat protein of wild-type cowpea chlorotic mottle
      virus has been nearly completely determined by direct methods. The sites of amino
      acid replacements were identified in the coat proteins of an oxidation-sensitive
      mutant, a temperature-sensitive mutant, and a salt-stable mutant. The
      replacements are a cysteinyl residue for the arginyl residue at position 25 in
      the oxidation-sensitive mutant, glutamic acid and alanine, respectively, for
      lysine and valine at positions 21 and 87 in the temperature-sensitive mutant, and
      arginine for lysine at position 105 in the salt-stable mutant. The substitutions
      are consistent with point mutations.

PMID- 18635151
TI  - When figure-ground segmentation modulates brightness: the case of phantom
      illumination.
AB  - In the phantom illumination illusion, luminance ramps ranging from black to white
      induce a brightness enhancement on an otherwise homogeneous dark background. The
      strength of the illusion was tested with regard to the extension of the
      brightness inducing perimeter, surrounding the target area by manipulating the
      number of inducers (exp. 1) and the size of the inducers (exp. 2). Participants'
      task was to rate the difference in brightness between the target area and the
      background. Results show that the illusion occurs only when the target area is
      not completely segregated from the background by luminance ramps; vice versa,
      when the target area is delimited by a continuous gradient, it appears darker
      than the background. These findings suggest a major role of figure-ground
      organization in the appearance of the illusion. This hypothesis was tested in a
      rating task experiment with three types of target area shapes circumscribed by
      four types of edges: luminance contours, illusory contours, no contours, and
      ambiguous contours. Illusory contours, just as luminance contours, hinder the
      illusion and produce a darkening of the target area. A control experiment
      measured the brightness of the previous stimuli without luminance ramps: all
      configurations resulted in a darkening of the target area. Results from all
      experiments suggest that figure-ground segmentation plays a major role in the
      determination of both illumination and lightness in stimuli with luminance
      gradients.

PMID- 18635152
TI  - Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection
      in humans.
AB  - PURPOSE: To investigate intraocular concentrations and pharmacokinetics of
      bevacizumab after a single intravitreal injection in humans. DESIGN: Prospective,
      noncomparative, interventional case series. METHODS: We included 30
      nonvitrectomized eyes of 30 patients (age range, 43 to 93 years) diagnosed with
      clinically significant cataract and concurrent macular edema secondary to
      neovascular age-related macular degeneration, diabetic retinopathy, or retinal
      venous occlusion in the same eye. All patients received an intravitreal injection
      of 1.5 mg bevacizumab. Between one and 53 days after injection, an aqueous humor
      sample was obtained during elective cataract surgery. Concentrations of unbound
      bevacizumab in these samples were quantified by enzyme-linked immunosorbent
      assay. RESULTS: Concentration of bevacizumab in aqueous humor peaked on the first
      day after injection with a mean concentration (c(max)) of 33.3 microg/ml (range,
      16.6 to 42.5 microg/ml) and subsequently declined in a monoexponential fashion.
      Nonlinear regression analysis determined an elimination half-time (t(1/2)) of
      9.82 days (R(2) = 0.81). No significant differences between diagnosis subgroups
      were noted. CONCLUSIONS: In human nonvitrectomized eyes, the aqueous half-life of
      1.5 mg intravitreally injected bevacizumab is 9.82 days.

PMID- 18635153
TI  - A pilot study of Fourier-domain optical coherence tomography of retinal dystrophy
      patients.
AB  - PURPOSE: To characterize the macular anatomy of retinal dystrophy eyes using high
      speed, high-resolution, Fourier-domain optical coherence tomography (FD-OCT).
      DESIGN: Case-control study. METHODS: Retinal dystrophy patients and normal age-
      and gender-matched controls underwent FD-OCT imaging using the RTVue (Optovue
      Inc., Fremont, California, USA). Vertical and horizontal 8-mm scans of 1024
      lines/cross-section were obtained. Based on boundaries manually drawn on computer
      displays of OCT cross-sections, the thicknesses of the retina, inner retinal
      layer (IRL), and outer retinal layer (ORL) were averaged over both 5-mm (macular)
      and 1.5-mm (foveal) regions centered at the fovea. The IRL was the sum of nerve
      fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL)
      thicknesses. Total retinal thickness (RT) was measured between the internal
      limiting membrane (ILM) and the retinal pigment epithelium. ORL thickness was
      calculated by subtracting IRL thickness from RT. RESULTS: Fourteen patients
      (three retinitis pigmentosa, two cone-rod degeneration, two Stargardt disease,
      and seven normal controls) underwent FD-OCT imaging. Mean foveal RT was 271.3 +/-
      23.3 microm for controls and 158.4 +/- 47.1 microm for retinal dystrophy patients
      (P < .001). Mean macular RT was 292.8 +/- 8.1 microm for controls and 199.1 +/-
      32.6 microm for retinal dystrophy patients (P < .001). Mean macular ORL was 182.9
      +/- 4.7 microm for controls and 101.3 +/- 18.7 microm for retinal dystrophy
      patients (P < .001); mean macular IRL was 109.9 +/- 6.4 microm for controls and
      97.9 +/- 20.7 microm for retinal dystrophy patients (P = .06). CONCLUSION: Eyes
      with retinal dystrophy had a small (11%) decrease in macular IRL and severe (45%)
      decrease in macular ORL compared to normal controls.

PMID- 18635154
TI  - [Fatal hydatid pulmonary embolism. Report of two cases].
AB  - Hydatid pulmonary embolism is rare but serious. The cause is usually the rupture
      of a cyst in the right cardiac chambers and less frequently the opening of an
      hepatic cyst into the venous circulation. We report two cases of hydatid
      pulmonary embolism following the rupture of a cyst in the right atrial cavity in
      one case and fistulisation of an hepatic cyst into the inferior vena cava in the
      second case. The course is dramatic in the two cases.

PMID- 18635155
TI  - Effect of lavender aroma on salivary endocrinological stress markers.
AB  - OBJECTIVE: We evaluated the stress relief effect of lavender aroma by measuring
      sensitive salivary endocrinological stress markers, cortisol and chromogranin A
      (CgA). DESIGN: Thirty healthy students performed a serial arithmetic task for
      10min and then rested for 10min. During the resting period, 16 students (aroma
      group) were exposed to airborne organic essential oil of lavender. Saliva samples
      were collected immediately before and after the arithmetic task, and at 5 and
      10min after that. Salivary cortisol and CgA levels were determined by enzyme
      linked immunosorbent assay. RESULTS: In the aroma group, levels of CgA that had
      been elevated at the end of the arithmetic task were statistically significantly
      lower 10min later. The control group showed no such change. During the protocol,
      no statistically significant changes in levels of cortisol were detected in
      either the aroma group or the control group. CONCLUSIONS: These findings suggest
      that lavender aroma has a stress relief effect.

PMID- 18635156
TI  - Early post-stressor intervention with high-dose corticosterone attenuates
      posttraumatic stress response in an animal model of posttraumatic stress
      disorder.
AB  - BACKGROUND: The therapeutic value of corticosteroids in the aftermath of
      traumatic experience has been questioned. We used an animal model of
      posttraumatic stress disorder (PTSD) to assess long-term behavioral effects of a
      single administration of various doses of corticosterone (CORT), administered
      immediately after exposure to psychogenic stress. METHODS: Animals were exposed
      to predator scent stress and treated 1 hour later with various doses of CORT or
      saline. The outcome measures included behavior in an elevated plus-maze (EPM) and
      acoustic startle response (ASR) 30 days after the initial exposure and freezing
      behavior upon exposure to a trauma-related cue on day 31. Pre-set cut-off
      behavioral criteria (CBC) classified exposed animals according to behavioral
      responses in EPM and ASR paradigms as those with "extreme behavioral response,"
      "minimal behavioral response," or "intermediate response." Non-spatial memory
      task and 24-hour locomotor activity were assessed immediately after injection
      with CORT or vehicle. RESULTS: Early treatment with high-dose CORT reduced the
      prevalence of PTSD-like behavioral responses relative to saline-control
      treatment. Cue-induced freezing was significantly lower in the high-dose CORT
      treated group. Lower doses of CORT significantly increased anxiety-like behavior,
      mean startle amplitude, and prevalence of PTSD-like behavioral disruptions,
      compared with saline-control treatment. The attenuated cue-responsiveness and
      impaired performance on a memory task imply that one key factor in this effect is
      the disruption of traumatic memory consolidation. CONCLUSIONS: Single treatment
      with high-dose CORT immediately after stressful exposure reduces the prevalence
      rate of extreme behavioral disruption 30 days later. Corticosterone might disrupt
      the consolidation of aversive or fearful memories.

PMID- 18635158
TI  - Regioselective synthesis of 4azido-Neu2en5,7Ac(2)1Me and its intramolecular
      transformation to 4azido-Neu2en5,9Ac(2)1Me.
AB  - Methyl 5-N-acetyl-7-O-acetyl-4-azido-2,3-didehydro-2,4-dideoxy-neuraminic acid
      (4azido-Neu2en5,7 Ac(2)1Me) was synthesized regioselectively starting from 4azido
      Neu2en5Ac1Me in high yield. The transformation of 4azido-Neu2en5,7Ac(2)1Me to the
      corresponding thermodynamically stable 4azido-Neu2en5,9Ac(2)1Me via
      intramolecular acetyl migration was confirmed by single-crystal X-ray diffraction
      analysis. The proposed rearrangement mechanism is discussed.

PMID- 18635157
TI  - Pretreatment brain activation during stroop task is associated with outcomes in
      cocaine-dependent patients.
AB  - BACKGROUND: Cognitive behavioral and related therapies for cocaine dependence may
      exert their effects, in part, by enhancing cognitive control over drug use
      behavior. No prior studies have systematically examined the neural correlates of
      cognitive control as related to treatment outcomes for cocaine dependence.
      METHODS: Twenty treatment-seeking cocaine-dependent individuals performed a
      Stroop color-word interference task while undergoing functional magnetic
      resonance imaging (fMRI) prior to initiating treatment. The primary outcome
      measures were percent of urine drug screens negative for cocaine, percent days
      abstinent, and treatment retention. Correlations between regional brain
      activation during Stroop task performance and treatment outcome measures were
      analyzed. RESULTS: During Stroop performance, individuals activated brain regions
      similar to those reported in nonaddicted individuals, including the anterior
      cingulate cortex, dorsolateral prefrontal cortex, parietal lobule, insula, and
      striatum. Activations at treatment onset correlated differentially with specific
      outcomes: longer duration of self-reported abstinence correlated with activation
      of ventromedial prefrontal cortex, left posterior cingulate cortex, and right
      striatum; percent drug-free urine screens correlated with striatal activation;
      and treatment retention correlated with diminished activation of dorsolateral
      prefrontal cortex. A modest correlation between Stroop effect and treatment
      retention was found. CONCLUSIONS: The functions of specific brain regions
      underlying cognitive control relate differentially to discrete outcomes for the
      treatment of cocaine dependence. These findings implicate neurocircuitry
      underlying cognitive control in behavioral treatment outcome and provide insight
      into the mechanisms of behavioral therapies for cocaine dependence. They also
      suggest neural activation patterns during cognitive control tasks are more
      sensitive predictors of treatment response than behavioral measures.

PMID- 18635159
TI  - Hydrogen bond formation in regioselectively functionalized 3-mono-O-methyl
      cellulose.
AB  - The hydrogen bond systems of cellulose and its derivatives are one of the most
      important factors regarding their physical- and chemical properties such as
      solubility, crystallinity, gel formation, and resistance to enzymatic
      degradation. In this paper, it was attempted to clarify the intra- and
      intermolecular hydrogen bond formation in regioselectively functionalized 3-mono
      O-methyl cellulose (3MC). First, the 3MC was synthesized and the cast film
      thereof was characterized in comparison to 2,3-di-O-methyl cellulose, 6-mono-O
      methyl cellulose, and 2,3,6-tri-O-methyl cellulose by means of wide angle X-ray
      diffraction (WAXD) and (13)C cross polarization/magic angle spinning NMR
      spectroscopy. Second, the hydrogen bonds in the 3MC film were analyzed by means
      of FTIR spectroscopy in combination with a curve fitting method. After
      deconvolution, the resulting two main bands (Fig. 3) indicated that instead of
      intramolecular hydrogen bonds between position OH-3 and O-5 another
      intramolecular hydrogen bond between OH-2 and OH-6 may exist. The large
      deconvoluted band at 3340cm(-1) referred to strong interchain hydrogen bonds
      involving the hydroxyl groups at C-6. The crystallinity of 54% calculated from
      the WAXD supports also the dependency of the usually observed crystallization in
      cellulose of the hydroxyl groups at C-6 to engage in interchain hydrogen bonding.

PMID- 18635160
TI  - Thymic alterations in Plasmodium berghei-infected mice.
AB  - The primary function of the thymus is to develop immature T-cells into cells that
      further in the periphery will be able to carry out immune functions. The
      Literature has shown that thymus can be a target for many pathogens and severe
      structural alterations take place in this organ during infectious diseases. Here,
      we investigated if thymus is also a target organ during experimental malaria
      infection by analyzing the presence of parasites inside the organ and
      histological alterations in thymuses from Plasmodium berghei NK65-infected
      BALB/c. After 14 days of infection, parasites were found inside the thymus that
      presented a profound atrophy with total loss of its architecture. We propose that
      the presence of parasites in the thymus induces histological modifications that
      alter the microenvironment, impairing by consequence the successful T cell
      development. Additional studies are currently being developed in our laboratory
      to verify if such thymic alterations can influence the systemic immune response
      to the parasite.

PMID- 18635161
TI  - Apophenia, theory of mind and schizotypy: perceiving meaning and intentionality
      in randomness.
AB  - Impaired ability to correctly infer others' mental states ('Theory of Mind' -
      ToM) and the tendency to perceive meaning in unrelated events ('apophenia') have
      been implicated in vulnerability to schizophrenia. Sixty-three healthy
      participants completed three experimental tasks that provided indices of ToM and
      apophenia. The first task (Contingency) required participants to rate the
      strength of relationship between the movements of two shapes; in some conditions
      the movements were unrelated, in others the movement of one shape was contingent
      on that of the other. In the second task (Stories), participants answered
      questions on short stories with 'random', 'physical' or 'ToM' themes. The third
      task (Triangles) required participants to view and then describe the movement of
      triangles on a computer screen in 'random', 'physical' and 'ToM' conditions.
      Participants completed questionnaire measures of psychosis-proneness (the
      Schizotypal Personality Scale - STA) and delusional thinking style (Peters et al.
      Delusions Inventory - PDI-21). Little evidence was found on any of the tasks for
      an association between a specific deficit in ToM accuracy and any aspect of
      psychosis-proneness. On the Triangles task, schizotypal and delusion-prone
      participants spontaneously reported perceiving a greater number of associations
      in the random condition (apophenia). On both the Triangles and Contingency tasks,
      over-mentalizing was found to be associated with delusional thinking but not with
      general schizotypy. We speculate that over-mentalizing may be underpinned by a
      hyper-associative cognitive style, linked to an exaggeration of the normal human
      tendency to attribute mental states, rather than to dysfunction in the assessment
      of causality. Perceiving meaning in randomness and, more particularly,
      attributing mental states where none are indicated, may be important factors in
      the formation of paranormal and delusional beliefs.

PMID- 18635162
TI  - Psychological aspects of the alien contact experience.
AB  - Previous research has shown that people reporting contact with aliens, known as
      "experiencers", appear to have a different psychological profile compared to
      control participants. They show higher levels of dissociativity, absorption,
      paranormal belief and experience, and possibly fantasy proneness. They also
      appear to show greater susceptibility to false memories as assessed using the
      Deese/Roediger-McDermott technique. The present study reports an attempt to
      replicate these previous findings as well as assessing tendency to hallucinate
      and self-reported incidence of sleep paralysis in a sample of 19 UK-based
      experiencers and a control sample matched on age and gender. Experiencers were
      found to show higher levels of dissociativity, absorption, paranormal belief,
      paranormal experience, self-reported psychic ability, fantasy proneness, tendency
      to hallucinate, and self-reported incidence of sleep paralysis. No significant
      differences were found between the groups in terms of susceptibility to false
      memories. Implications of the results are discussed and suggestions are made for
      future avenues of research.

PMID- 18635163
TI  - The "Haunt" project: an attempt to build a "haunted" room by manipulating complex
      electromagnetic fields and infrasound.
AB  - Recent research has suggested that a number of environmental factors may be
      associated with a tendency for susceptible individuals to report mildly anomalous
      sensations typically associated with "haunted" locations, including a sense of
      presence, feeling dizzy, inexplicable smells, and so on. Factors that may be
      associated with such sensations include fluctuations in the electromagnetic field
      (EMF) and the presence of infrasound. A review of such work is presented,
      followed by the results of the "Haunt" project in which an attempt was made to
      construct an artificial "haunted" room by systematically varying such
      environmental factors. Participants (N=79) were required to spend 50 min in a
      specially constructed chamber, within which they were exposed to infrasound,
      complex EMFs, both or neither. They were informed in advance that during this
      period they might experience anomalous sensations and asked to record on a floor
      plan their location at the time of occurrence of any such sensations, along with
      a note of the time of occurrence and a brief description of the sensation. Upon
      completing the session in the experimental chamber, they were asked to complete
      three questionnaires. The first was an EXIT scale asking respondents to indicate
      whether or not they had experienced particular anomalous sensations. The second
      was the Australian Sheep-Goat Scale, a widely used measure of belief in and
      experience of the paranormal. The third was Persinger's Personal Philosophy
      Inventory, although only the items that constitute the Temporal Lobe Signs (TLS)
      Inventory sub-scale were scored. These items deal with psychological experiences
      typically associated with temporal lobe epilepsy but normally distributed
      throughout the general population. Although many participants reported anomalous
      sensations of various kinds, the number reported was unrelated to experimental
      condition but was related to TLS scores. The most parsimonious explanation for
      our findings is in terms of suggestibility.

PMID- 18635164
TI  - Studying connections in the living human brain with diffusion MRI.
AB  - The purpose of this article is to explain how the random walks of water molecules
      undergoing diffusion in living tissue may be exploited to garner information on
      the white matter of the human brain and its connections. We discuss the concepts
      underlying diffusion-weighted (DW) imaging, and diffusion tensor imaging before
      exploring fibre tracking, or tractography, which aims to reconstruct the three
      dimensional trajectories of white matter fibres non-invasively. The two main
      classes of algorithm - deterministic and probabilistic tracking - are compared
      and example results are presented. We then discuss methods to resolve the
      'crossing fibre' issue which presents a problem when using the tensor model to
      characterize diffusion behaviour in complex tissue. Finally, we detail some of
      the issues that remain to be resolved before we can reliably characterize
      connections of the living human brain in vivo.

PMID- 18635165
TI  - A novel compound from Casearia esculenta (Roxb.) root and its effect on
      carbohydrate metabolism in streptozotocin-diabetic rats.
AB  - Casearia esculenta root (Roxb.) is widely used in traditional system of medicine
      to treat diabetes in India. An active compound 3-hydroxymethyl xylitol (3-HMX)
      has been isolated and its optimum dose has been determined in a short duration
      study and patented. In the present study, the long-term effect of 3-HMX in type 2
      diabetic rats has been investigated. An optimum dose of 3-HMX (40 mg/kg body
      weight) was orally administered for 45 days to streptozotocin-diabetic rats for
      the assessment of glucose, insulin, hemoglobin (Hb), glycated hemoglobin
      (HbA(1c)), hepatic glycogen, and activities of carbohydrate metabolizing enzymes,
      such as glucokinase, glucose 6-phosphatase, fructose 1,6-bisphosphatase and
      glucose-6-phosphate dehydrogenase and hepatic marker enzymes, such as aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
      (ALP) and gammaglutamyl transferase (GGT) in normal and streptozotocin-diabetic
      rats. 3-HMX at 40 mg dose produced similar effects on all biochemical parameters
      studied as that of glibenclamide, a standard drug. Histological study of pancreas
      also confirmed the biochemical findings. These results indicate that 3
      hydroxymethyl xylitol, the compound from C. esculenta, possesses
      antihyperglycemic effect on long-term treatment also.

PMID- 18635166
TI  - Laminin alpha 5 mediates ectopic adhesion of hepatocellular carcinoma through
      integrins and/or Lutheran/basal cell adhesion molecule.
AB  - Laminins are a diverse group of alpha/beta/gamma heterotrimers formed from five
      alpha, three beta and three gamma chains; they are major components of all basal
      laminae (BLs). One laminin chain that has garnered particular interest due to its
      widespread expression pattern and importance during development is laminin alpha
      5. Little is known, however, about the expression and function of laminins
      containing the alpha 5 chain in human hepatocellular carcinoma (HCC). Here, using
      a specific antibody, we examined the expression of laminin alpha 5 in normal
      liver and in HCCs. In normal liver, although laminin alpha 5 was observed in
      hepatic BLs underlying blood vessels and bile ducts, it was absent from the
      parenchyma, which may be the origin of HCC. On the other hand, laminin alpha 5
      deposition was observed throughout all HCCs tested, regardless of tumor grade. In
      well-differentiated HCCs, it localized along the trabecules of the tumor. In
      poorly-differentiated HCCs, it was present in surrounding tumor nodules. In HCC
      cell lines, laminin alpha 5 heterotrimerized with beta and gamma chains and was
      secreted into the culture media. To attempt to understand the function of
      laminins containing alpha 5, the expression of its receptors in HCCs was also
      determined. In this regard, alpha 3 beta 1/alpha 6 beta 1 integrins and
      Lutheran/basal cell adhesion molecule (Lu/B-CAM) were expressed in HCC cells. In
      vitro studies showed that HCC cells readily attached to laminin containing the
      alpha 5 chain, more so than did primary hepatocytes. In addition to alpha 3 beta
      1/alpha 6 beta 1 integrins and Lu/B-CAM, laminin alpha 5 was recognized by
      integrin alpha 1 beta 1, which also was expressed in HCC cells. These results
      suggest that laminins containing alpha 5 serve as functional substrates
      regulating progression of HCC.

PMID- 18635167
TI  - Maternal virilization due to luteoma associated with delayed lactation.
AB  - OBJECTIVE: To report on a patient with virilization during pregnancy who
      experienced delayed lactation secondary to elevated maternal androgens. DESIGN:
      Case report and review of the literature. SETTING: University hospital.
      PATIENT(S): A 32-year-old pregnant woman presented with virilization at 32 weeks'
      gestation. INTERVENTION(S): Laboratory evaluation, ultrasound examination,
      magnetic resonance imaging, cesarean section for fetal indication, nipple
      stimulation to facilitate lactation. MAIN OUTCOME MEASURE(S): Case report.
      RESULT(S): Postpartum normalization of serum T levels and patient ability to
      breastfeed exclusively after delayed initiation of lactation. CONCLUSION(S):
      Maternal virilization during pregnancy is rare and is often due to androgen
      secreting tumors that are benign. Therefore, careful evaluation of these patients
      is important to avoid inadvertent oophorectomy.

PMID- 18635168
TI  - Chlamydia trachomatis infection in women with secondary infertility.
AB  - OBJECTIVE: To assess the role of Chlamydia in secondary infertility in a
      prospective study. DESIGN: Forty women with secondary infertility and 30 healthy
      term pregnant women of similar age composition were studied for past and present
      Chlamydia trachomatis infection. SETTING: Women attending the outpatient
      Department of Obstetrics and Gynaecology with complaint of secondary infertility
      were enrolled as patients in the study. PATIENT(S): Forty women with secondary
      infertility formed the study group, and 30 healthy women served as the controls.
      INTERVENTION(S): Chlamydia IgG was detected by ELISA; titers of 1:320 or more
      were considered positive. Endocervical swabs were collected for culture on
      cycloheximide-treated McCoy cell lines, and ELISA was used to detect Chlamydia
      antigen. Hysterosalpingography was performed to assess tubal patency. MAIN
      OUTCOME MEASURE(S): A difference was expected between the prevalence of C.
      trachomatis infection in the infertile study subjects and fertile control group.
      RESULT(S): Immunoglobulin G antibodies were present in 22 (55%) women with
      secondary infertility, whereas positivity was seen among 2 (5.5%) controls. Tubal
      occlusion occurred in 16 (63.6%) cases positive for chlamydial antibody.
      Sensitivity of chlamydial IgG antibody as a diagnostic marker for infertility was
      72.7%, and specificity was 44.4%. The majority of Chlamydia IgG antibody-positive
      cases, 17 (77.2%), were symptomatic. Unfavorable obstetric history was found in
      16 (72.7%) cases. Active infection was found in 12 (30%) cases with one (3.3%)
      case of current infection occurring in the controls. CONCLUSION(S): Prevalence of
      past chlamydial infection is strongly statistically significant in women with
      secondary infertility. Current infection was also found statistically
      significantly in these women. Immunoglobulin G antibody detection is an effective
      and noninvasive tool for detection of Chlamydia and a more viable option than HSG
      in a developing country such as India. Screening of women with secondary
      infertility for C. trachomatis is strongly recommended to allow early therapeutic
      interventions.

PMID- 18635170
TI  - Serum interleukin-8 levels are elevated in patients with ovarian endometrioma.
AB  - OBJECTIVE: To determine whether serum interleukin (IL)-8 concentration can be
      measured in patients with ovarian endometrioma and whether this measurement is a
      useful tool in diagnosing this disease. DESIGN: A controlled clinical study and
      an in vitro study. SETTING: Department of Obstetrics and Gynecology, Tottori
      University, Japan. PATIENT(S): Seventy patients with ovarian endometrioma and 21
      patients with benign ovarian cyst. INTERVENTION(S): Laparoscopic surgery or
      laparotomy for ovarian endometriomas or benign ovarian cyst was performed.
      Preoperative blood samples were obtained. Endometriotic stromal cells obtained
      from nine patients with endometrioma were cultured. MAIN OUTCOME MEASURE(S):
      Interleukin-8 concentration in the serum or supernatant of the cell culture was
      measured with use of ELISA. RESULT(S): The serum concentration of IL-8 in
      patients with endometrioma was significantly higher than in patients with benign
      ovarian cyst. The serum IL-8 threshold (25 pg/mL) had a higher sensitivity
      (71.4%) for diagnosing ovarian endometrioma than did serum CA-125 level. The
      increased rates of IL-8 concentration in the culture supernatants after adding
      tumor necrosis factor alpha were significantly higher in patients whose serum IL
      8 levels were >or=25 pg/mL than in those with levels <25 pg/mL. CONCLUSION(S):
      Measuring of serum IL-8 concentration may be a valuable tool in diagnosing
      endometriosis.

PMID- 18635169
TI  - Abnormal uterine bleeding: a review of patient-based outcome measures.
AB  - OBJECTIVE: To summarize and evaluate the patient-based outcome measures (PBOMs)
      that have been used to study women with abnormal uterine bleeding (AUB). DESIGN:
      Systematic review. SETTING: Original articles that used at least one PBOM and
      were conducted within a population of women with AUB. PATIENT(S): Women with AUB.
      INTERVENTION(S): The titles, abstracts, and studies were systematically reviewed
      for eligibility. The PBOMs used in eligible studies were summarized. Essential
      psychometric properties were identified, and a list of criteria for each property
      was generated. MAIN OUTCOME MEASURE(S): "Quality" of individual PBOMs as
      determined using the listed criteria for psychometric properties. RESULT(S): Nine
      hundred eighty-three studies referenced AUB and patient-reported outcomes. Of
      these, 80 studies met the eligibility criteria. Fifty different instruments were
      used to evaluate amount of bleeding, bleeding-related symptoms, or menstrual
      bleeding-specific quality of life. The quality of each of these instruments was
      evaluated on eight psychometric properties. The majority of instruments had no
      documentation of reliability, precision, or feasibility. There was no
      satisfactory evidence that any one instrument completely addressed all eight
      psychometric properties. CONCLUSION(S): Studies of women with AUB are
      increasingly using PBOMs. Many different PBOMs were used; however, no single
      instrument completely addressed eight important measurement properties.

PMID- 18635171
TI  - Secondary linitis plastica of the rectum: EUS features and tissue diagnosis (with
      video).
AB  - BACKGROUND: Luminal metastases to the GI tract may be seen at the time of the
      primary diagnosis or may represent evidence of a distant recurrence. OBJECTIVES:
      To determine the prevalence of rectal-wall metastases in patients undergoing an
      EUS and to describe the EUS features and yield of EUS-guided FNA (EUS-FNA) and
      Trucut biopsy (TCB). DESIGN: A case series. SETTING: A single tertiary-referral
      center. PATIENTS: Patients undergoing lower GI (LGI) EUS from July 1, 2005, to
      October 31, 2007. INTERVENTION: EUS-FNA and/or TCB. MAIN OUTCOME MEASUREMENTS:
      EUS features and cytologic and/or histologic confirmation of secondary rectal
      linitis plastica. RESULTS: Over the 28-month period, an LGI-EUS was performed in
      598 patients with presumed primary rectal cancer, of whom 6 (1%) were diagnosed
      with rectal-wall metastases. The EUS features were that of diffuse,
      circumferential, hypoechoic wall-thickening that mimics that of linitis plastica,
      breaching the muscularis propria in all cases. EUS-FNA and/or TCB of the rectal
      wall or perirectal lymph node established a diagnosis in all cases. The primary
      cancers originated from the bladder (n = 3), breast (n = 1), stomach (n = 1), and
      a right forearm cutaneous melanoma (n = 1). The time interval from the initial
      primary cancer diagnosis to that of GI-tract rectal metastasis ranged from 0 days
      (simultaneous diagnoses) to 119 months (mean +/- SD 49 +/- 43 months).
      LIMITATIONS: Although firm EUS criteria of rectal-wall metastases cannot be
      established based on 6 patients alone, certain features may prove useful for the
      diagnosis in the clinical practice. CONCLUSIONS: EUS-FNA and/or TCB can confirm
      the diagnosis of secondary linitis plastica of the rectum.

PMID- 18635172
TI  - Closure of a gastrotomy after transgastric tubal ligation by using the Eagle Claw
      VII: a survival experiment in a porcine model (with video).
AB  - BACKGROUND: Transgastric access to the peritoneal cavity presents new
      opportunities for novel endoscopic surgery. Secure closure of the gastrotomy site
      is critical to the success of transgastric endoscopic surgery. OBJECTIVE: To
      study the safety and efficacy of closure of a gastrotomy by using the Eagle Claw
      VII endoscopic suturing device after transgastric bilateral tubal ligation.
      DESIGN: A prospective survival study in a porcine model with ten 30-kg pigs.
      INTERVENTIONS: The gastrotomies were made by using a needle-knife and balloon
      dilation. Bilateral fallopian tube ligation was performed with detachable snares,
      and the tubes were transected by using the needle-knife. The gastrotomies were
      closed with endoscopic suturing by using the Eagle Claw VII. MAIN OUTCOME
      MEASUREMENTS: Included the survival of the pigs, security of the closure, number
      of plicating sutures used, operative time, peritoneal contamination, and
      histopathologic confirmation of the full-thickness healing of the gastrotomy.
      RESULTS: Transgastric fallopian-tube ligation was performed in 10 pigs, and all
      of the gastrotomies were successfully closed by using the Eagle Claw VII
      endoscopic suturing device. The operative time for bilateral tubal ligation was
      38.2 minutes (range 18-50 minutes), whereas, the operative time for gastrotomy
      closure was 25.5 minutes (range 15-35 minutes). Three endoscopic sutures were
      necessary to achieve a secure gastrotomy closure. All the pigs survived and
      tolerated a full diet 24 hours after the operation. A postmortem confirmed full
      thickness healing for all gastrotomies, with no evidence of leakage. One pig had
      an overtube-related esophageal perforation, which was successfully managed with
      endoscopic clip closure. LIMITATIONS: The porcine gastric wall is thicker than
      the human gastric wall, and the posterior wall of the porcine stomach becomes the
      anterior-inferior wall after gaseous distention. Hence, all the gastrotomies were
      made through the posterior wall. The tissue tolerance and healing of the porcine
      stomach may be different from that of the human stomach. CONCLUSIONS: Endoscopic
      suturing by using the Eagle Claw VII device is a feasible method for gastrotomy
      closure after a natural orifice transluminal endoscopic surgery procedure.

PMID- 18635173
TI  - The safety and effectiveness of endoscopic biliary decompression by plastic stent
      placement in acute suppurative cholangitis compared with nasobiliary drainage.
AB  - BACKGROUND: Endoscopic retrograde biliary drainage (ERBD) by using a plastic
      stent is suggested to be as effective as endoscopic nasobiliary drainage (ENBD)
      for temporary biliary drainage in acute suppurative cholangitis (ASC). However,
      there are few studies that compared ERBD and ENBD in ASC. OBJECTIVES: We compared
      the safety and efficacy of ERBD and ENBD for temporary biliary drainage in
      patients with ASC. DESIGN: A case series. SETTING: A tertiary-referral center.
      PATIENTS AND INTERVENTIONS: Eighty patients with ASC underwent endoscopic biliary
      drainage with ENBD (n = 41) and ERBD (n = 39). MAIN OUTCOME MEASUREMENT: Clinical
      outcomes, including complications related to ERCP and complications related to
      the type of the indwelling catheter. RESULTS: Endoscopic biliary drainage was
      successfully achieved in all patients (100%). There were no significant
      differences in the demographic data between the 2 groups. There were no
      differences in the improvement of clinical and laboratory parameters between the
      2 groups. Overall ERCP-related complication rates in the ENBD and ERBD groups
      were 31.7% and 38.5%, respectively (P = .527). Hyperamylasemia occurred in 18
      patients, 12.2% in the ENBD group (5/41) and 33.3% in the ERBD group (13/39) (P =
      .024). Without endoscopic sphincterotomy (EST), there was no statistically
      significant difference in the incidence of hyperamylasemia between the 2 groups.
      However, with an EST, hyperamylasemia was more frequent in the ERBD group (12/28
      [42.9%]) than in the ENBD group (3/27 [11.1%]) (P = .008). LIMITATION: A single
      center experience. CONCLUSIONS: Endoscopic biliary decompression, whether by ERBD
      or ENBD, is an effective treatment for patients with ASC. However, more frequent
      hyperamylasemia with ERBD and EST deserves further evaluation.

PMID- 18635174
TI  - Influence of juxtapapillary diverticula on the success or difficulty of
      cannulation and complication rate.
AB  - BACKGROUND: Periampullary diverticula (PAD) are found in 9% to 32% of patients
      who undergo an ERCP. Published studies confer conflicting results regarding the
      true impact of PAD on the technical success and complications of ERCP. OBJECTIVE:
      The aim of the study was to investigate and compare success rate, difficulty at
      cannulation, and complications between patients with and without PAD, as well as
      to identify independent factors that influence the difficulty at cannulation.
      DESIGN: A prospective study. SETTING: Tzaneio General Hospital. PATIENTS: A total
      of 601 consecutive patients who underwent an ERCP were divided into 2 groups
      according to the presence (group A, 117 patients) or absence (group B, 484
      patients) of PAD. Patients with undetectable papilla were excluded from the study
      cohort. The incidence of undetectable papilla was 8.3% in patients with duodenal
      diverticula and 0.9% in patients without duodenal diverticula (P = .000).
      RESULTS: Successful cannulation was achieved in up to 94.9% and 94.8% in groups A
      and B, respectively. The effort and difficulty at attempting this goal was
      different between the groups (43.5% vs 59.1%, P = .003), because patients without
      PAD were subjected to more vigorous attempts or even the pre-cut technique to
      attain a cholangiogram. There was no significant difference between the groups in
      the complication rate either in total or in any particular patient. Multivariate
      logistic regression analysis showed 3 of the variables, namely
      choledocholithiasis, abnormal papilla, and the presence of diverticula, remained
      significant, and all of them presented with odds ratios indicating an easier
      cannulation attempt. LIMITATION: A nonrandomized study. CONCLUSIONS: The finding
      of a periampullary diverticulum during an ERCP should not be considered an
      obstacle to a successful cannulation and, furthermore, may be an indicator of an
      easier cannulation attempt, provided that the papilla can be found with
      confidence. Concerns about increased complications are not substantiated in this
      study.

PMID- 18635175
TI  - Live video manipulator for endoscopy and natural orifice transluminal endoscopic
      surgery (with videos).
AB  - BACKGROUND: During fluoroscopy, radiologists and gastroenterologists are able to
      manipulate live fluoroscopic video for better orientation and visualization.
      During endoscopy and natural orifice transluminal endoscopic surgery (NOTES),
      this function is not currently available. Particularly during NOTES, the
      endoscopic image is sometimes inverted, and off-axis operation is required.
      OBJECTIVE: Our purpose was to develop and test a prototype live video manipulator
      (LVM) for endoscopy, laparoscopy, and NOTES. DESIGN: Prospective ex vivo and in
      vivo feasibility study. INTERVENTIONS: We developed a prototype LVM software for
      video image manipulation that can be easily installed on any computer. The video
      input is streamed into the computer and can be displayed on a standard monitor.
      LVM was tested ex vivo in the following functions: (1) instant live video
      rotation, (2) vertical or horizontal video inversion, (3) mirror imaging, and (4)
      digital zooming. These functions were also tested during upper and lower GI
      endoscopy, ERCP, diagnostic laparoscopy, and various transvaginal NOTES
      procedures (cholecystectomy, gastroenterostomy, and sleeve gastrectomy) in
      porcine models. MAIN OUTCOME MEASUREMENTS: Image quality observation between
      unmanipulated and manipulated live videos. RESULTS: LVM reliably and easily
      performed live video manipulation during these tests. Besides standard definition
      video signals, LVM is fully compatible with high-definition video endoscopy.
      Three observers reported that the subjective image quality was the same in
      specified areas between manipulated and unmanipulated live videos. LIMITATIONS:
      Observation and feasibility study. CONCLUSIONS: LVM reliably and conveniently
      performed live video manipulations. LVM requires minimal equipment, capital
      investment, and maintenance, and is easy to set up. LVM can be a useful tool in
      many medical imaging studies, including endoscopy, laparoscopy, and NOTES, either
      as a built-in technology or as an as-needed add-on feature.

PMID- 18635176
TI  - EUS in localizing safe alternate access sites for natural orifice transluminal
      endoscopic surgery: initial experience in a porcine model.
AB  - BACKGROUND: Most natural orifice transluminal endoscopic surgery (NOTES)
      procedures have been performed through the anterior stomach wall, based on the
      established safety of PEG placement. This approach does not afford mechanically
      efficient access to all anatomic areas of interest. OBJECTIVE: To assess the
      utility of EUS in identifying safe alternate access sites for NOTES. DESIGN:
      Nonsurvival animal experiment. METHODS: Thirty-two EUS-guided access procedures
      were performed through the antrum, the posterior stomach wall, or the rectum of
      12 pigs. Sixteen safe-access procedures (SAP) used sonographic guidance to
      achieve safe intraperitoneal access by avoiding extraluminal organs and vessels
      during the initial NOTES puncture. Sixteen unsafe-access procedures (UAP)
      evaluated potential complications of blind access by performing a standard NOTES
      puncture at sites adjacent to critical extraluminal structures identified by EUS.
      Access was achieved by using a similar technique for both SAPs and UAPs. Baseline
      and completion laparotomies were performed. RESULTS: All 16 UAPs resulted in
      clinically relevant complications, such as liver laceration and iliac artery
      injury. In contrast, 13 SAPs were without complication. The 3 complications in
      the SAP group occurred with transrectal access and consisted of 2 minor
      complications and a small-bowel perforation. CONCLUSIONS: Blind NOTES access
      through the antrum, posterior stomach wall, and rectum could result in
      catastrophic complications. In contrast, EUS-guided access through these sites
      substantially reduced but did not completely eliminate this risk. EUS appears
      promising as an adjunct to NOTES access, particularly as more experience is
      gained in definitively excluding the presence of at-risk extraluminal structures.

PMID- 18635177
TI  - Percutaneous transhepatic biliary drainage may serve as a successful rescue
      procedure in failed cases of endoscopic therapy for a post-living donor liver
      transplantation biliary stricture.
AB  - BACKGROUND: Although a biliary stricture is one of the most important
      complications that develop after living donor liver transplantation (LDLT), a
      standard approach has not yet been established. OBJECTIVE: The aim of this study
      was to evaluate the usefulness of nonoperative management in repairing a post
      LDLT biliary stricture. DESIGN: A total of 60 patients were referred, from July
      2004 to July 2007, for management of a post-LDLT biliary stricture. The patients
      had ERCP if the hepatic arterial flow was patent on a Doppler sonography. If
      endoscopic therapy failed, then percutaneous transhepatic drainage (PTBD) was
      performed to dilate the stricture. If the percutaneous approach also failed, then
      a repeated PTBD was performed after a 3-dimensional abdominal CT (3D-CT).
      SETTING: Division of Gastroenterology, Department of Internal Medicine, Yongdong
      Severance Hospital. PATIENTS: Sixty patients were referred from Catholic
      University Hospital of Korea for ERCP. RESULTS: ERCP was performed on all 60
      patients, and 38 (63%) were successfully treated. When the shape of the distal
      side of the bile-duct anastomosis was classified into 3 categories (pouched,
      triangular, and intermediate), the pouched shape showed the lowest success rate
      of endoscopic therapy (25% [4/16]). Fifteen of 22 patients in whom endoscopic
      therapy failed were treated by using PTBD. Nine of the 15 patients were
      successfully managed in the first PTBD attempt, and 4 of the 6 patients in whom
      the first attempt of PTBD failed had repeated PTBD after a 3D-CT. Four patients
      were successfully treated with repeated PTBD of the alternative branch approach
      after a 3D-CT. CONCLUSIONS: ERCP is a feasible first modality in the treatment of
      a post-LDLT biliary stricture, but, in failed cases, especially in the pouched
      shape, PTBD can be attempted. When initial PTBD trial fails, a biliary-tract
      examination, such as a 3D-CT, can be useful for a repeated PTBD trial.

PMID- 18635178
TI  - Erythropoietin improves oxidative stress following spinal cord trauma in rats.
AB  - Spinal cord injury (SCI) is a very destructive process for both patients and
      society. Lipid peroxidation is the main cause of the further secondary damage
      which starts after mechanical destruction of tissues. Recent studies have shown
      that erythropoietin (EPO) has neuroprotective properties. In this study, we aimed
      to see the effect of EPO treatment after spinal cord injury on the oxidant and
      anti-oxidant enzyme systems and the relationship with the N-methyl-D-Aspartate
      (NMDA) blockage. Spinal cord injury was produced by epidural compression with a
      cerebral vascular clip that has a closing force of 40 g for 30s after a limited
      multilevel laminectomy (T9-11). Experiment was done in 5 groups: Group 1: Sham
      operated untraumatised, Group 2: SCI untreated, Group 3: 150 i.u./kg EPO injected
      i.p. at the end of the first hour following the trauma. Group 4: NMDA receptor
      antagonist ketamine (100mg/kg) i.p. Group 5: EPO+ketamine i.p. The experiments
      were finished after 12h of the trauma. The spinal cords were excised for
      biochemical examinations. Anti-oxidant enzymes; catalase and reduced glutathione
      (GSH) levels increased and lipid peroxidation product, malonyldialdehyde (MDA)
      level decreased in EPO treated group when compared to the other groups. TNF-alpha
      levels decreased in EPO treated group. Application of ketamine before EPO
      treatment decreased effects of EPO. In conclusion, our results suggest that 150
      i.u./kg i.p. EPO, a therapeutic dose in anaemic patients, applied after 1h of
      spinal cord injury significantly attenuated the oxidative damage of spinal cord
      injuries in rats. This activity is abolished via ketamine pretreatment.

PMID- 18635179
TI  - Injury and pre-hospital trauma care in Hanoi, Vietnam.
AB  - BACKGROUND: In Vietnam, injury is the leading cause of death in children under
      18, and road traffic accidents are the fifth leading cause of death. Information
      systems for pre-hospital trauma care are insufficient. OBJECTIVES: The objective
      of this study was to assess injury morbidity and mortality, and the existing
      level of pre-hospital trauma care in Hanoi city. RESEARCH DESIGN AND SUBJECTS: A
      cross-sectional study was conducted in seven districts in Hanoi in 2006. We
      studied 2800 households (11,334 members), 9 hospitals and an emergency service
      centre. RESULTS: The injury morbidity rate was 1134/100,000 (year(-1)), and the
      injury mortality rate was 23.7/100,000 (year(-1)). There was no significant
      difference in age or sex between injury severity levels (p>0.05). Road traffic
      accidents were the leading cause of injury. Causes of injury mortality differed
      among different age groups. Only 4% of injured cases were transported to hospital
      by ambulance. Fifty-two percent of victims did not receive first aid at the site.
      Pre-hospital trauma care was separately provided by the emergency service centre
      and hospitals. There was no communication network between the emergency service
      centre and hospitals, ambulances and hospitals, or between different hospitals.
      CONCLUSIONS: The results reveal that injury is a major health problem in Hanoi
      and that the pre-hospital care system lacks both coordination and many vital
      components. Study results may assist decision-makers in identifying interventions
      to improve health and safety for the population of Hanoi.

PMID- 18635180
TI  - Human defensins and cytokines in vaginal lavage fluid of women with bacterial
      vaginosis.
AB  - OBJECTIVE: To measure the concentrations of interferon gamma (IFN-gamma),
      interleukin (IL)-2, IL-4, IL-5, human beta-defensin 2 (HBD-2), and human defensin
      5 (HD-5) in the vaginal lavage fluid (VLF) of healthy women and women with
      bacterial vaginosis (BV). METHODS: VLF samples were obtained from 73 women with
      BV, 15 women with intermediate vaginal flora, 33 healthy women with vaginal pH
      greater than or equal to 4.5, and a control group of 39 healthy women with
      vaginal pH less than 4.5. The concentrations of IFN-gamma, IL-2, IL-4, IL-5, HBD
      2, and HD-5 were measured using enzyme-linked immunosorbent assay kits. RESULTS:
      Concentrations of HBD-2 and HD-5 in the VLF of women with BV were significantly
      higher than in the control group (P<0.05). IL-4 concentration was significantly
      lower in the VLF of women with BV than in the control group (P<0.05).
      CONCLUSIONS: HBD-2 and HD-5 may be involved in defending against invasion by BV
      related microorganisms and the decrease in IL-4 concentration may increase
      susceptibility to BV.

PMID- 18635181
TI  - Two cases describing the effects of hypothyroidism on puberty and growth.

PMID- 18635182
TI  - Somatization and psychological distress among women with vulvar vestibulitis
      syndrome.
AB  - OBJECTIVE: To investigate the distribution of psychological characteristics and
      pain reporting among women with vulvar vestibulitis syndrome (VVS). METHODS: In
      this exploratory study, 109 women with VVS completed a battery of questionnaires
      to assess pain with intercourse and psychological characteristics (e.g.
      somatization, anxiety, distress). The distribution of these characteristics was
      compared, first with a conventional binary classification schema (primary and
      secondary) and subsequently with a 3-category schema (primary, latent primary,
      secondary). RESULTS: Severity of pain with intercourse did not differ among the
      subgroups using either classification schema. Women with primary VVS consistently
      showed higher levels of somatization, anxiety, and distress compared with those
      with secondary VVS. Using a 3-tiered classification system, we found no
      difference between latent primary diagnosis and the other 2 groups (primary and
      secondary). CONCLUSION: This study highlights the critical need for research on
      subtype definition and the role of psychological factors in VVS.

PMID- 18635183
TI  - Clinical and metabolic effects of medroxyprogesterone acetate and ethinyl
      estradiol plus drospirenone in women with polycystic ovary syndrome.
AB  - OBJECTIVES: To investigate the effects of treatment with medroxyprogesterone
      acetate (MPA), 10 days per month for 6 months, on lipid and carbohydrate
      metabolism in women with polycystic ovary syndrome (PCOS). METHODS: Sixty-three
      women with PCOS were randomized to receive MPA or ethinyl estradiol plus
      drospirenone. RESULTS: There were no changes in lipid or carbohydrate metabolism
      in the MPA group, but serum levels of luteinizing hormone (P<0.001) and total
      testosterone (P<0.003) significantly decreased, as did the free androgen index
      (P<0.02) and acne (P<0.03) and seborrhea (P<0.04) scores. In the ethinyl
      estradiol plus drospirenone group lipid and hormone values significantly
      increased whereas acne, seborrhea, hair loss, and Ferriman-Gallwey scores
      decreased. There was no statistically significant change in the total cholesterol
      to high-density cholesterol ratio in either group. CONCLUSION: Treatment of PCOS
      patients with MPA provided good menstrual cycle control, beneficial changes in
      hormonal values associated with hyperandrogenism, and no significant changes in
      lipid or carbohydrate metabolism.

PMID- 18635184
TI  - Pregnancy complicated by myocardial infarction.

PMID- 18635185
TI  - Granulocytic sarcoma of the uterus.

PMID- 18635186
TI  - Synchronous primary carcinoma of the cervix and endometrium with early lymph node
      recurrence.

PMID- 18635187
TI  - High in vitro fertilization discontinuation rate in France.

PMID- 18635188
TI  - Pravastatin reduces the risk for cardiovascular disease in Japanese
      hypercholesterolemic patients with impaired fasting glucose or diabetes: diabetes
      subanalysis of the Management of Elevated Cholesterol in the Primary Prevention
      Group of Adult Japanese (MEGA) Study.
AB  - Diabetes mellitus (DM) is a major risk factor for cardiovascular disease (CVD) in
      patients with no history of CVD. Evidence for the effect of statins on CVD in the
      diabetic population in low-risk populations (e.g., Japanese) is limited. We
      evaluated the effect of pravastatin on risk reduction of CVD related to baseline
      glucose status in a primary prevention setting. The Management of Elevated
      Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study, in
      patients with mild-to-moderate hypercholesterolemia (220-270 mg/dL), showed that
      low-dose pravastatin significantly reduced the risk for CVD by 26%. This
      exploratory subanalyses examined the efficacy of diet plus pravastatin on CVD in
      2210 patients with abnormal fasting glucose (AFG, including 1746 patients with DM
      and 464 patients with impaired fasting glucose (IFG) at 5 years in the MEGA
      Study. CVD was threefold higher in AFG patients (threefold higher in DM, and
      twofold higher in IFG) compared with normal fasting glucose (NFG) patients in the
      diet group. Diet plus pravastatin treatment significantly reduced the risk of CVD
      by 32% (hazard ratio 0.68, 95% CI 0.48-0.96, number needed to treat, 42) in the
      AFG group compared with the diet alone group, and no significant interaction
      between AFG and NFG (interaction P=0.85) was found. Safety problems were not
      observed during long-term treatment with pravastatin. In conclusion, pravastatin
      reduces the risk of CVD in subjects with hypercholesterolemia and abnormal
      fasting glucose in the primary prevention setting in Japan.

PMID- 18635189
TI  - Circulating oxidized LDL, measured with FOH1a/DLH3 antibody, is associated with
      metabolic syndrome and the coronary heart disease risk score in healthy Japanese.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to clarify the
      relationship between circulating oxidized LDL (oxLDL) and metabolic syndrome (MS)
      and the coronary heart disease (CHD) risk score. METHODS: We conducted a cross
      sectional study of healthy volunteers who had no signs, symptoms or history of
      cardiovascular or cerebrovascular disease and took no medications. We studied 382
      Japanese volunteers, 190 men and 192 women (median age 41 and 38 years,
      respectively). We used an ELISA kit and a monoclonal oxLDL antibody, FOH1a/DLH3,
      to measure circulating oxLDL. RESULTS: The odds ratio (OR) for elevated oxLDL in
      individuals with MS compared to those without MS, adjusted for age and sex, was
      1.94 (range 1.00-3.78). In individuals with a predicted Framingham 10-year risk
      for CHD>5% (corresponding with the highest quartile), compared to those with a
      predicted 10-year risk<5%, the OR, adjusted for age, sex, smoking, and LDL
      cholesterol, was 2.51 (1.17-5.36). The age-, sex-, smoking- and LDL cholesterol
      adjusted OR for a 10-year CHD risk score >5% was 1.03 (1.01-1.04) for LDL
      cholesterol and 11.7 (4.69-29.0) for smoking. CONCLUSIONS: Elevated oxLDL is
      associated with the presence of MS and the CHD risk score in healthy people.

PMID- 18635190
TI  - Multipurpose peptide tags for protein isolation.
AB  - A multifunctional peptide tag (HYDHYD) consisting of histidine, tyrosine and
      aspartate residues was fused to the N-terminal ends of green fluorescent protein
      (GFP), lactate dehydrogenase (LDH) and human hemoglobin (Hb), proteins which were
      subjected to ion-exchange chromatography (IEC), aqueous two-phase system
      partition, immobilized metal-ion affinity chromatography (IMAC), and hydrophobic
      interaction chromatography (HIC). Tagged GFP was retained significantly longer
      (>1 column volume) in both HIC and IEC. It exhibited 3x greater partition in
      favor of the hydrophobic phase in a two-phase system and 96% could be bound to an
      IMAC column which did not bind native GFP.

PMID- 18635191
TI  - Photodegradation of E110 and E122 dyes in a commercial aperitif. A high
      performance liquid chromatography-diode array-tandem mass spectrometry study.
AB  - A commercial aperitif containing E110 and E122 dyes is exposed to photo
      irradiation in solar box under conditions chosen to simulate sun light
      irradiation. After 16 days of irradiation the red-coloured aperitif assumes a
      very pale yellow colour. HPLC-diode array-MS/MS analysis evidences the presence
      in the commercial aperitif of some impurities with naphthalene-based structures.
      The structures for the photodegradation products are proposed.

PMID- 18635192
TI  - Analytical methods for the determination of bisphenol A in food.
AB  - Food constitutes the primary route for human exposure to bisphenol A (BPA), one
      of the highest volume chemicals produced worldwide. The estrogenic properties of
      BPA, its wide dispersive use and the recent extensive literature describing low
      dose BPA effects in animals, have raised concerns about its possible adverse
      effects on human health. A reliable health risk assessment of BPA relies
      basically on its unambiguous identification and accurate quantification in food,
      and the aim of the present review is to give an overview of the analytical
      methods reported so far for the determination of BPA in these matrices. Emphasis
      is placed on the main strategies developed for sample treatment, which usually
      consists of several laborious and time-consuming steps in order to achieve the
      required sensitivity and selectivity. Separation, identification and quantitation
      of BPA is today reliably made with mass spectrometric methods, namely liquid
      chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry
      (GC-MS), and thus main attention is devoted to these techniques, but other
      methods using LC coupled to fluorescence or electrochemical detection, as well as
      immunochemical methods are also covered. Recent and expected future developments
      are discussed.

PMID- 18635193
TI  - Imitative learning from a third-party interaction: relations with self
      recognition and perspective taking.
AB  - Young children's ability to learn something new from a third-party interaction
      may be related to the ability to imagine themselves in the third-party
      interaction. This imaginative ability presupposes an understanding of self-other
      equivalence, which is manifested in an objective understanding of the self and an
      understanding of others' subjective perspectives. The current study measured
      imitative learning of a novel action seen only in a third-party interaction,
      mirror self-recognition, and perspective taking in a group of 48 18- to 20-month
      olds. Patterns of performance suggest that understanding self-other equivalence
      is related to third-party learning.

PMID- 18635194
TI  - Kinetics of adhesion mediated by extracellular loops of claudin-2 as revealed by
      single-molecule force spectroscopy.
AB  - Claudins (Cldns) comprise a large family of important transmembrane proteins that
      localize at tight junctions where they play a central role in regulating
      paracellular transportation of solutes across epithelia. However, molecular
      interactions occurring between the extracellular domains of these proteins are
      poorly understood. Here, using atomic force microscopy, the adhesion strength and
      kinetic properties of the homophilic interactions between the two extracellular
      loops of Cldn2 (C2E1or C2E2) and full-length Cldn2 were characterized at the
      level of single molecule. Results show that while the first extracellular loop is
      sufficient for Cldn2/Cldn2 trans-interaction, the second extracellular loop does
      not interact with the full-length Cldn2, with the first extracellular loop, or
      with itself. Furthermore, within the range of loading rates probed (10(2)-10(4)
      pN/s), dissociation of Cldn2/Cldn2 and C2E1/C2E1 complexes follows a two-step
      energy barrier model. The difference in activation energy for the inner and outer
      barriers of Cldn2/Cldn2 and C2E1/C2E1 dissociation was found to be 0.26 and 1.66
      k(B)T, respectively. Comparison of adhesion kinetics further revealed that
      Cldn2/Cldn2 dissociates at a much faster rate than C2E1/C2E1, indicating that the
      second extracellular loop probably has an antagonistic effect on the kinetic
      stability of Cldn2-mediated interactions. These results provide an insight into
      the importance of the first extracellular loop in trans-interaction of Cldn2
      mediated adhesion.

PMID- 18635195
TI  - Dissecting NGF interactions with TrkA and p75 receptors by structural and
      functional studies of an anti-NGF neutralizing antibody.
AB  - The anti-nerve growth factor (NGF) monoclonal antibody alphaD11 is a potent
      antagonist that neutralizes the biological functions of its antigen in vivo. NGF
      antagonism is expected to be a highly effective and safe therapeutic approach in
      many pain states. A comprehensive functional and structural analysis of alphaD11
      monoclonal antibody was carried out, showing its ability to neutralize NGF
      binding to either tropomyosine receptor kinase A (TrkA) or p75 receptors. The 3-D
      structure of the alphaD11 Fab fragment was solved at 1.7 A resolution. A
      computational docking model of the alphaD11 Fab-NGF complex, based on epitope
      mapping using a pool of 44 NGF mutants and experimentally validated by small
      angle X-ray scattering, provided the structural basis for identifying the
      residues involved in alphaD11 Fab binding. The present study pinpoints loop II of
      NGF to be an important structural determinant for NGF biological activity
      mediated by TrkA receptor.

PMID- 18635196
TI  - Spinal subdural hematoma following tissue plasminogen activator treatment for
      acute ischemic stroke.
AB  - A 49-year-old woman with an acute ischemic stroke was treated by the intravenous
      administration of tissue plasminogen activator within 2 h of symptom onset. She
      complained of severe upper thoracic back pain the following day. Progressive
      paraparesis was detected on the third admission day. Spinal MRI demonstrated an
      acute anterior subdural hematoma from the C7 to T2 level. An urgent laminectomy
      was performed. Neurologists must be aware of the possibility that neck or back
      pain after thrombolysis for ischemic stroke may be the first presenting symptom
      of spinal hematoma.

PMID- 18635215
TI  - Validation of the Fournier's gangrene severity index in a large contemporary
      series.
AB  - PURPOSE: In this study we identified prognostic factors for survival and
      validated the accuracy of the Fournier's gangrene severity index in patients with
      Fournier's gangrene. MATERIALS AND METHODS: We retrospectively reviewed medical
      records of patients diagnosed with Fournier's gangrene between 1996 and 2006.
      Fournier's gangrene severity index scores were assessed using a receiver
      operating characteristic curve. Using an outcome variable of inpatient mortality,
      univariate analyses were performed using the Mann-Whitney U, chi-square and
      Fisher exact tests. RESULTS: A total of 68 patients (79.4% male, mean age 55.8 +/
      15.2 years) diagnosed with Fournier's gangrene met the criteria for review. The
      inpatient mortality rate was 10% (7 patients). The mean Fournier's gangrene
      severity index score for survivors was 5.4 +/- 3.5 vs 10.9 +/- 4.7 for
      nonsurvivors (p = 0.006). Isolated Fournier's gangrene severity index and
      individual laboratory parameters associated with mortality included heart rate (p
      = 0.05), respiratory rate (p = 0.02), serum creatinine (p = 0.03), serum
      bicarbonate (p = 0.001), serum lactate (p = 0.001) and serum calcium (p = 0.03).
      Although mean total body surface area was only suggestive of an association (p =
      0.169), abdominal wall (p = 0.004) or lower extremity (p = 0.005) involvement was
      associated with increased mortality. Using a Fournier's gangrene severity index
      score threshold of 9 (sensitivity 71.4%, specificity 90%) there was a 96%
      survival rate in patients with a Fournier's gangrene severity index of less than
      9 and a 46% mortality rate in those with a Fournier's gangrene severity index of
      9 or greater (p = 0.001, OR 22, 95% CI 3.5-139.7). CONCLUSIONS: The Fournier's
      gangrene severity index remains an objective and simple method to quantify the
      extent of metabolic aberration at presentation in patients with Fournier's
      gangrene. A Fournier's gangrene severity index threshold value of 9 is sensitive
      and specific for predicting mortality in this patient population.

PMID- 18635216
TI  - Evaluation of current TNM classification of penile carcinoma.
AB  - PURPOSE: The TNM classification is the most common tool for staging malignancies.
      The current classification for penile carcinoma has been unchanged since 1987.
      There are several shortcomings to this classification. Accurate clinical staging
      can be troublesome because several categories are defined by anatomical
      structures that cannot readily be identified by physical examination or imaging.
      A second drawback is substantial variability with respect to survival in certain
      T and N categories. We analyzed the prognostic value of the TNM classification in
      patients with penile carcinoma treated at our institute. We propose modifications
      to improve prognostic stratification and facilitate clinical staging. MATERIALS
      AND METHODS: The records of 513 patients treated between 1956 and 2006 were
      analyzed. All tumors were staged according to the most recent classification. We
      calculated disease specific survival in the different T and N categories.
      Survival in the different categories was compared using Kaplan-Meier analysis and
      the log rank test. RESULTS: Five-year disease specific survival in the entire
      group was 80.5% at a median followup of 58.7 months. There was no significant
      difference in survival between T2 and T3 tumors (p = 0.57). Furthermore, no
      significant survival difference was found between N1 and N2 categories (p =
      0.18). Using a modified classification a significant difference in survival was
      found among all T and N categories. CONCLUSIONS: The current TNM classification
      for penile carcinoma does not adequately differentiate in terms of survival among
      several T and N categories. With some modifications prognostic stratification
      improves and clinical staging is facilitated.

PMID- 18635217
TI  - The impact of prostate gland weight in robot assisted laparoscopic radical
      prostatectomy.
AB  - PURPOSE: We determined whether prostate weight has an impact on the pathological
      and operative outcomes of robot assisted laparoscopic radical prostatectomy.
      MATERIALS AND METHODS: We reviewed the records of 1,847 consecutive patients who
      underwent robot assisted laparoscopic radical prostatectomy at our institution.
      Variables were compared across quartile distributions of prostate size as defined
      by weight, including group 1-less than 30 gm, group 2-30 to 49.9, group 3-50 to
      69.9 and group 4-70 or greater. Factors assessed in this analysis were patient
      age, body mass index, prostate specific antigen, Gleason score, pathological
      stage, margin status, operative time, blood loss, transfusion rate, length of
      stay and rehospitalization rate. RESULTS: Patients with a larger prostate (group
      4) were older (mean age 66.2 years), had higher pretreatment prostate specific
      antigen (median 6.5 ng/ml), lower Gleason score (mean 6.3), longer operative time
      (mean 3.2 hours), higher estimated blood loss (median 250 cc) and longer hospital
      stay (p = 0.0002). There was a trend toward higher risk disease based on D'Amico
      risk stratification and positive margin status in group 1, although evidence of
      extracapsular extension was more common in groups 2 and 3. There was no
      association between prostate size and body mass index, lymph node status, blood
      transfusion rate, seminal vesicle involvement and rehospitalization rate.
      CONCLUSIONS: Robot assisted laparoscopic radical prostatectomy in patients with
      an enlarged prostate is feasible with slightly longer operative time, urinary
      leakage rates and hospital stay. Pathologically larger prostates are generally
      associated with lower Gleason score and risk group stratification. One-year
      continence rates and biochemical recurrence rates are similar across all groups.

PMID- 18635218
TI  - Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that
      relapsed after initial maximum androgen blockade.
AB  - PURPOSE: Large meta-analyses have documented that maximum androgen blockade with
      nonsteroidal antiandrogens for advanced prostate cancer confers survival
      benefits, although it remains controversial. Also, we and others have reported
      the effectiveness of second line hormonal therapy for prostate cancer that
      relapses after initial hormone therapy. However, there is little clinical
      evidence of the effectiveness of the latter treatment strategy. Therefore, in
      this multicenter trial in Japan we analyzed clinical outcomes following
      alternative changing from 1 nonsteroidal antiandrogen to another, ie bicalutamide
      to flutamide and flutamide to bicalutamide, for advanced prostate cancer that
      relapsed after initial maximum androgen blockade. MATERIALS AND METHODS: The
      study included 232 patients with advanced prostate cancer who were initially
      treated with maximum androgen blockade, including surgical or medical castration
      combined with nonsteroidal antiandrogens. If a patient relapsed while on first
      line therapy, we discontinued antiandrogen and evaluated the patient for
      antiandrogen withdrawal syndrome. We then administered an alternative
      antiandrogen and evaluated its effect. RESULTS: The incidence of antiandrogen
      withdrawal syndrome after initial maximum androgen blockade was 15.5% for
      bicalutamide and 12.8% for flutamide. A prostate specific antigen decrease after
      antiandrogen withdrawal was a prognostic factor. Nonsteroidal antiandrogens as
      alternative therapy in patients with relapse after the initial maximum androgen
      blockade were effective (prostate specific antigen decrease greater than 50%) as
      second line maximum androgen blockade. Of 232 patients 142 (61.2%) showed a
      prostate specific antigen decrease in response to an alternative antiandrogen.
      These responders had significantly better survival than nonresponders, suggesting
      that responsiveness to second line therapy predicts increased survival.
      CONCLUSIONS: Following maximum androgen blockade with an alternative nonsteroidal
      antiandrogen is effective for advanced prostate cancer that has relapsed after
      initial maximum androgen blockade. Even a partial response to second line maximum
      androgen blockade was associated with improved survival. Our data support the
      notion that responders to second line regimens are androgen independent but still
      hormonally sensitive.

PMID- 18635219
TI  - Finnish multicenter study comparing intermittent to continuous androgen
      deprivation for advanced prostate cancer: interim analysis of prognostic markers
      affecting initial response to androgen deprivation.
AB  - PURPOSE: Intermittent androgen deprivation has been proposed to prolong hormone
      sensitivity and improve quality of life in patients with advanced prostate
      cancer. The FinnProstate Study VII has been performed to identify patients who
      might benefit from intermittent androgen deprivation. In this interim analysis we
      evaluated which prognostic markers affect the initial response to androgen
      deprivation therapy. MATERIALS AND METHODS: A total of 856 men with locally
      advanced or metastatic prostate cancer were enrolled and given androgen
      deprivation therapy for 24 weeks to ensure hormone sensitivity. Patients with
      hormone sensitive prostate cancer were randomized 1:1 to continuous androgen
      deprivation or intermittent androgen deprivation. The randomization criteria were
      prostate specific antigen decrease to less than 10 ng/ml or by more than 50% if
      less than 20 ng/ml at baseline. RESULTS: There were 292 patients (34%) who did
      not meet the randomization criteria (group 1). The remaining 564 patients (66%)
      were randomized to intermittent androgen deprivation or continuous androgen
      deprivation (group 2). Mean prostate specific antigen (834 vs 151 ng/ml), mean
      alkaline phosphatase (793 vs 292 IU/l), proportion of T4 tumors (37% vs 24%),
      poorly differentiated cancers (39% vs 26%), metastatic disease (82% vs 51%) and
      number of skeletal hot spots in M1 disease (more than 5 hot spots 72% vs 42%)
      were significantly higher in group 1 than in group 2. CONCLUSIONS: Patients with
      the most advanced prostate cancer and poorest prognosis do not show adequate
      biochemical prostate specific antigen response to androgen deprivation therapy
      but should be assessed for eligibility to receive nonendocrine treatment.

PMID- 18635220
TI  - Risk of prostate cancer after diagnosis of atypical glands suspicious for
      carcinoma on saturation and traditional biopsies.
AB  - PURPOSE: Prostatic glandular atypia is present in approximately 5% of traditional
      template biopsy specimens. Prior reports suggest this finding carries a 40% risk
      of prostate cancer on subsequent biopsy. We determined the risk of malignancy in
      patients with atypia diagnosed on saturation biopsy. MATERIALS AND METHODS: We
      identified 57 patients with a diagnosis of atypia who underwent repeat biopsy
      between January 2001 and August 2007. Charts were reviewed for clinical and
      pathological information. RESULTS: Median patient age was 62 years (range 46 to
      79). Of the 57 patients 19 (33%) had atypia diagnosed on saturation biopsy (20
      cores or greater) (group 1), whereas 38 (67%) had atypia diagnosed with a more
      traditional biopsy technique (12 cores or fewer) (group 2). All patients
      subsequently underwent saturation repeat biopsy a median of 5 months after the
      original biopsy. Eight group 1 patients (42%) were found to have cancer on
      rebiopsy compared to 15 (39.5%) in group 2 (p = 1.00). Whereas only 1 of the 8
      patients (12.5%) with cancer in group 1 had a Gleason score of 7 or greater, this
      was found in 5 of the 15 (33%) in group 2 (p = 0.37). Interestingly patients with
      cancer were less likely to have inflammation on initial biopsy (p = 0.05).
      CONCLUSIONS: The finding of atypia on prostate biopsy is associated with a high
      likelihood of underlying malignancy regardless of the number of cores taken on
      initial biopsy. Inflammation in the initial biopsy may create a false-positive
      finding of atypia.

PMID- 18635221
TI  - Validation of Partin tables and development of a preoperative nomogram for
      Japanese patients with clinically localized prostate cancer using 2005
      International Society of Urological Pathology consensus on Gleason grading: data
      from the Clinicopathological Research Group for Localized Prostate Cancer.
AB  - PURPOSE: We validated the 2001 Partin tables and developed an original nomogram
      for Japanese patients using the 2005 International Society of Urological
      Pathology consensus on Gleason grading. MATERIALS AND METHODS: Prostatectomy
      specimens from 1,188 Japanese men who underwent radical prostatectomy for
      clinically localized prostate cancer (cT1-2) between 1997 and 2005 were analyzed.
      Polychotomous logistic regression analysis was used to construct a nomogram to
      predict final pathological stage (organ confined disease, extraprostatic
      extension, seminal vesicle invasion and lymph node involvement) from 3 variables,
      including serum prostate specific antigen, clinical stage and biopsy Gleason
      score. The area under the ROC curve was used to compare the new nomogram with the
      Partin tables. RESULTS: Preoperative serum prostate specific antigen and biopsy
      Gleason score were higher in the Japanese cohort than in the Partin cohort. The
      distribution of clinical and final pathological stages was similar in the 2
      cohorts. The AUC for predicting organ confined disease was 0.699 and 0.717 for
      data applied to the Partin tables and to the new nomogram, respectively. The AUC
      for predicting lymph node involvement was 0.793 and 0.863, respectively.
      CONCLUSIONS: To our knowledge this is the first preoperative nomogram developed
      for clinically localized prostate cancer in Japanese patients. Although the new
      nomogram predicted the pathological stage of prostate cancer in Japanese patients
      more accurately than the Partin tables, it did not satisfactorily predict organ
      confined disease. However, other predictive variables, such as more detailed
      pathological features of biopsy specimens or magnetic resonance imaging, may
      further improve prediction accuracy.

PMID- 18635222
TI  - External validation of the updated Partin tables in a cohort of North American
      men.
AB  - PURPOSE: The Partin tables were updated in 2007. However, to our knowledge their
      accuracy and performance characteristics have not been confirmed in an external
      validation cohort. MATERIALS AND METHODS: We examined the discrimination and
      calibration properties of the 2007 Partin tables in 1,838 men treated with
      radical prostatectomy between 2001 and 2005 at Cleveland Clinic Foundation. The
      ROC derived AUC and the Brier score were used to quantify the discriminant
      properties of the predictions of the 2007 Partin tables for extraprostatic
      extension, seminal vesical invasion and lymph node invasion. Loess based
      calibration plots were used to examine the relationship between the predicted and
      observed rates of extraprostatic extension, seminal vesical invasion and lymph
      node invasion. RESULTS: The rates of extraprostatic extension, seminal vesical
      invasion and lymph node invasion were 26.9%, 5.5% and 1.8%. The accuracy of
      extraprostatic extension, seminal vesical invasion and lymph node invasion
      prediction was 71%, 80% and 75% according to the AUC method, and 0.176, 0.051 and
      0.037 according to the Brier score, respectively. Extraprostatic extension
      predictions between 0% and 25%, and lymph node invasion predictions between 0%
      and 5% correlated well with observed extraprostatic extension and lymph node
      invasion rates, respectively. Conversely a suboptimal correlation was recorded
      between predicted and observed seminal vesical invasion rates as well as between
      predicted and observed rates of extraprostatic extension and lymph node invasion
      for predicted extraprostatic extension and lymph node invasion values above 25%
      and 5%, respectively. CONCLUSIONS: In this examined validation cohort the overall
      accuracy (AUC) of the Partin tables was comparable to results reported in the
      original 2007 development cohort. However, performance characteristics indicate
      that predictions within specific probability ranges should be interpreted with
      caution.

PMID- 18635223
TI  - Multiplicity and history have a detrimental effect on survival of patients with
      T1G3 bladder tumors selected for conservative treatment.
AB  - PURPOSE: In the absence of Tis tumor we assessed whether history and multiplicity
      have a detrimental effect on conservative treatment in carefully selected
      patients with T1G3 bladder carcinoma. MATERIALS AND METHODS: Between January 1976
      and December 1999, 165 select patients with T1G3 bladder tumors were
      conservatively treated with transurethral resection plus adjuvant intravesical
      therapy. Patients with concomitant or previous Tis, previous T1G3, tumor size
      greater than 3 cm and more than 3 lesions were excluded from analysis. Repeat
      transurethral resection was not routinely performed. However, cytology had to be
      negative for atypia before the start of adjuvant intravesical therapy. RESULTS:
      Recurrence-free survival at 1, 3 and 5 years was 71.8%, 55.6% and 45%,
      respectively. Of the cases 14 (8.4%) progressed with a median progression-free
      survival of 149 months. A total of 23 patients (14%) died. The 5-year recurrence
      free survival rate was 52%, 34% and 15% in cases of single and/or primary,
      multiple and recurrent tumors, respectively. Median overall survival was 144
      months. The 5-year disease-free overall survival rate was 85%, 83%, 79% and 69%
      in cases of primary, single, multiple and recurrent tumors, respectively. An
      intact bladder was maintained in 137 patients (83%) with a mean disease-free
      overall survival of 102.7 months. Patients with recurrent and/or multiple T1G3
      tumors showed worse survival (p = 0.0021 and 0.0142, respectively). CONCLUSIONS:
      History and multiplicity are relevant predictors of survival even in highly
      selected patients with TIG3 bladder tumors that are conservatively treated.

PMID- 18635224
TI  - The role of lymphovascular invasion in predicting the prognosis of clinically
      localized upper tract urothelial carcinoma (pT1-3cN0M0).
AB  - PURPOSE: We assessed the impact of lymphovascular invasion on the prognosis of
      patients treated for clinically localized (pT1-3N0M0) upper tract urothelial
      carcinoma. MATERIALS AND METHODS: From January 1998 to December 2004, 106
      patients treated surgically for clinically localized upper tract urothelial
      carcinoma (pT1-3cN0M0) were recruited for analysis retrospectively. We assessed
      the impact of multiple prognostic factors including age, sex, smoking, tumor
      multiplicity, pathological stage, grading, squamous differentiation, subsequent
      bladder tumor recurrence, tumor site and lymphovascular invasion on the
      recurrence-free survival rate. We clarified the role of lymphovascular invasion
      in predicting cancer specific survival in these patients. RESULTS: Mean patient
      age was 67.2 +/- 11.1 years and median followup was 47.5 months (range 40 to
      115). Lymphovascular invasion was present in 32 of 106 (30.2%) patients. The 5
      year recurrence-free survival rate in patients with and without lymphovascular
      invasion was 65.3% and 91.9%, respectively (p <0.001). On multivariate analysis
      lymphovascular invasion status, pT3 and ureteral involvement were significant
      predictors of patient recurrence-free survival. The positivity of lymphovascular
      invasion was also significantly associated with the risk of higher stage disease
      (OR 7.49). CONCLUSIONS: Patients with lymphovascular invasion had a higher risk
      of greater pathological stage disease. Lymphovascular invasion and high stage
      disease with ureteral involvement led to a greater risk of disease recurrence
      and, in turn, recurrence caused a higher mortality rate. This finding could help
      identify patients at greater risk for disease recurrence who would benefit from
      close followup and early adjuvant therapy.

PMID- 18635225
TI  - Risk score and metastasectomy independently impact prognosis of patients with
      recurrent renal cell carcinoma.
AB  - PURPOSE: We evaluated the prognostic roles of metastasectomy and an established
      risk stratification system in patients with disease recurrence following
      nephrectomy for nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: A
      retrospective analysis was performed in 129 patients with localized renal cell
      carcinoma treated with partial or radical nephrectomy and subsequently diagnosed
      with disease recurrence. At recurrence a previously validated risk score based on
      Karnofsky performance status, interval from nephrectomy, and serum hemoglobin,
      calcium and lactate dehydrogenase was used to categorize patients as being at
      favorable, intermediate or poor risk. Survival from time of recurrence was
      assessed based on risk categorization and metastasectomy. RESULTS: Median time
      from nephrectomy to recurrence was 16 months. The risk score was strongly
      associated with median survival and the 2-year survival rate, including 73 months
      and 81% for favorable risk, 28 months and 54% for intermediate risk, and 6 months
      and 11% for poor risk, respectively (log rank <0.001). Metastasectomy performed
      in 44 patients (34%) was found to be of clinical benefit across the various risk
      categories (interaction analysis p = 0.8). On multivariate analysis a better risk
      category and metastasectomy were each independently associated with more
      favorable survival (each p <0.001). When combined, they provided 6 risk
      categories with an estimated 2-year survival of 0% to 93%. CONCLUSIONS: The
      clinical course in patients with recurrent renal cell carcinoma following
      nephrectomy can be variable. It is independently impacted by an objectively
      determined risk score and whether the patient undergoes metastasectomy.

PMID- 18635226
TI  - A phase II trial of gemcitabine plus capecitabine for metastatic renal cell
      cancer previously treated with immunotherapy and targeted agents.
AB  - PURPOSE: We assessed the clinical activity and safety of gemcitabine plus
      capecitabine in patients with metastatic renal cell cancer previously treated
      with immunotherapy. MATERIALS AND METHODS: In this phase II trial patients
      received 1,000 mg/m(2) gemcitabine intravenously on days 1, 8 and 15, plus 830
      mg/m(2) capecitabine orally twice daily on days 1 to 21 of 28-day cycles. The
      primary end point was progression-free survival time. Secondary end points
      included overall survival time, objective response rate and toxicity. RESULTS: Of
      84 patients enrolled 83 were evaluable for response and toxicity. A total of 65
      patients had intermediate or poor risk prognosis. Median progression-free
      survival and overall survival were 4.6 (95% CI 3.7-7.3) and 17.9 months (95% CI
      13.2-23.6), respectively. There were 6 partial responses and 1 complete response
      (objective response rate 8.4% [95% CI 3.5-16.6]). Two patients remain in
      unmaintained remission close to 3 years from the initiation of gemcitabine plus
      capecitabine treatment. On multivariate analysis more than 3 disease sites were
      significantly associated with shorter progression-free survival and patients with
      thrombocytosis, more than 3 disease sites or anemia had a significantly increased
      risk of death. Adverse events occurring at least once in more than 5% of patients
      included grade 3 or greater neutropenia (83%), grade 2 or greater hand-foot
      syndrome (13%), grade 3 or greater thrombocytopenia (12%), grade 3 or greater
      thromboembolic events (8%), grade 3 or greater fatigue (8%) and grade 2 or
      greater mucositis (6%). CONCLUSIONS: At the doses and schedule tested gemcitabine
      plus capecitabine demonstrated modest clinical activity in metastatic renal cell
      cancer after cytokine failure and produced significant neutropenia. A modified
      gemcitabine plus capecitabine regimen may be evaluated in patients with
      metastatic renal cell cancer after failure of approved targeted therapies.

PMID- 18635228
TI  - Conversion during laparoscopic surgery: frequency, indications and risk factors.
AB  - PURPOSE: There are limited data on the indications for open conversion during
      laparoscopic surgery. The frequency of conversion for various procedures is
      poorly quantified and the degree to which this changes with time is not well
      understood. Risk factors for conversion are not defined. We addressed these
      issues in a large series of laparoscopic operations. MATERIALS AND METHODS: We
      reviewed our database of 2,128 laparoscopic operations performed between 1993 and
      2005, including radical nephrectomy in 549 patients, simple nephrectomy in 186,
      partial nephrectomy in 347, donor nephrectomy in 553, pyeloplasty in 301,
      nephroureterectomy in 106 and retroperitoneal lymph node dissection in 86. Open
      conversions were identified and the frequency of conversion for the total cohort
      and specific procedures was determined. Trends in conversion with time were
      assessed and indications analyzed. Clinicopathological features between patients
      requiring conversion and those who did not were compared. RESULTS: We identified
      68 patients (3.3%) who underwent conversion to open surgery (group 1) and 2,011
      (96.7%) who did not (group 2). The frequency of conversion was greatest during
      nephroureterectomy (8.49%), followed by simple nephrectomy (5.91%),
      retroperitoneal lymph node dissection (4.65%), partial nephrectomy (4.32%),
      radical nephrectomy (2.91%), donor nephrectomy (2.53%) and pyeloplasty (0.33%).
      The absolute number of conversions and conversions/cases performed per year
      decreased significantly with time, reaching a nadir of less than 1% per year.
      Conversion was inversely related to case volume and cumulative experience.
      Indications included vascular injury in 38.5% of cases, concern with margins in
      13.5%, bowel injury in 13.5%, failure to progress in 11.5%, adhesions in 9.6%,
      diaphragmatic injury in 1.9% and other in 11.5%. The distribution of indications
      remained similar with time. There were no differences in patient age, gender,
      surgical history, American Society of Anesthesiologists score or tumor stage
      between groups 1 and 2. In groups 1 and 2 mean operative time was 304 vs 219
      minutes and estimated blood loss was 904 vs 255 cc (each p <0.0001). CONCLUSIONS:
      The rate of conversion during laparoscopic surgery is not uniform across
      procedures and it is important for patient counseling. The most common indication
      for conversion is vascular injury. Importantly the frequency of conversion is
      dynamic and likely related to case volume and cumulative experience.

PMID- 18635227
TI  - von Hippel-Lindau gene status and response to vascular endothelial growth factor
      targeted therapy for metastatic clear cell renal cell carcinoma.
AB  - PURPOSE: The von Hippel-Lindau (VHL) gene is often inactivated (by mutation or
      promoter hypermethylation) in renal cell carcinoma but the relation to
      therapeutic outcome is unclear. MATERIALS AND METHODS: Patients with metastatic
      clear cell renal cell carcinoma with available baseline tumor samples who
      received vascular endothelial growth factor targeted therapy were included in
      analysis. Patient characteristics, VHL gene status and clinical outcome were
      documented. Our primary end point was to test for response rate in relation to
      VHL inactivation. Progression-free survival and overall survival in relation to
      VHL status were investigated as secondary end points. RESULTS: A total of 123
      patients were evaluable. Response rate, median progression-free survival and
      median overall survival were 37% (95% CI 28-46), 10.8 (95% CI 7.7-14.8) and 29.8
      (CI not estimable) months, respectively. Patients with VHL inactivation had a
      response rate of 41% vs 31% for those with wild-type VHL (p = 0.34). Patients
      with loss of function mutations (frameshift, nonsense, splice and in-frame
      deletions/insertions) had a 52% response rate vs 31% with wild-type VHL (p =
      0.04). On multivariate analysis the presence of a loss of function mutation
      remained an independent prognostic factor associated with improved response.
      Progression-free survival and overall survival were not significantly different
      based on VHL status. CONCLUSIONS: To our knowledge this is the largest analysis
      investigating the impact of VHL inactivation on the outcome of vascular
      endothelial growth factor targeted agents in metastatic renal cell carcinoma. We
      did not find a statistically significant increase in response to vascular
      endothelial growth factor targeted agents in patients with VHL inactivation. Loss
      of function mutations identified a population of patients with a greater
      response. Investigation of downstream markers is under way.

PMID- 18635229
TI  - Laparoscopic radical nephroureterectomy for upper tract transitional cell
      carcinoma: oncological outcomes at 7 years.
AB  - PURPOSE: We present long-term oncological outcomes following laparoscopic
      nephroureterectomy for upper tract transitional cell carcinoma. MATERIALS AND
      METHODS: Between December 1997 and August 2005, 100 patients underwent
      laparoscopic nephroureterectomy for upper tract transitional cell carcinoma at
      our institution. Data were obtained from a prospectively maintained database,
      patient charts, telephone followup and a review of the Social Security Death
      Index. RESULTS: Median patient age at surgery was 73 years. Final pathological
      stage was pTis/pTa in 28% of patients, pT1 in 31%, pT2 in 13%, pT3 in 24% and pT4
      in 4%. High grade lesions were present in 58% of patients, multifocal disease was
      present in 23% and lymphovascular invasion was present in 9%. Positive surgical
      margins occurred in 7 patients (7%). Median followup was 7 years (range 2 to 10).
      At 2, 5 and 7 years overall survival was 81%, 59% and 50%, cancer specific
      survival was 91%, 77% and 72%, and recurrence-free survival was 66%, 50% and 36%,
      respectively. Five-year cancer specific survival by stage was 80% for pTis/Ta,
      70% for pT1, 68% for pT2, 60% for pT3 and 0% for pT4. On univariate analysis
      nonorgan confined disease and lymphovascular invasion affected cancer specific
      survival (p = 0.01 and 0.04, respectively). On multivariate analysis only
      nonorgan confined disease was a significant factor (p = 0.04). Concomitant
      bladder tumor at diagnosis was associated with poor recurrence-free survival on
      univariate and multivariate analysis (p = 0.02 and 0.01, respectively).
      CONCLUSIONS: To our knowledge the largest long-term followup after laparoscopic
      nephroureterectomy for upper tract transitional cell carcinoma is presented. Long
      term oncological outcomes appear comparable to those of open surgery.

PMID- 18635230
TI  - Ultrasound guided percutaneous microwave ablation for small renal cancer: initial
      experience.
AB  - PURPOSE: We evaluated the feasibility, safety and efficacy of ultrasound guided
      percutaneous microwave ablation for small renal cell cancers. MATERIALS AND
      METHODS: A total of 12 patients with a pathologically proven renal cell cancer
      1.3 to 3.8 cm in diameter were treated with microwave ablation. A cooled shaft
      needle antenna was percutaneously inserted into the tumor under ultrasound
      guidance. One antenna was used for tumors 2 cm or smaller and antennae were used
      for tumors larger than 2 cm. One thermocouple was placed about 0.5 cm away from
      the tumor to monitor temperature in real time during ablation. Microwaves were
      emitted at 50 W for 500 seconds and prolonged as necessary to attain temperatures
      sufficient to ensure tumor kill. Immediate treatment efficacy was assessed by
      contrast enhanced ultrasound 1 day after ablation. Short-term efficacy was
      assessed by contrast enhanced computerized tomography and/or contrast enhanced
      ultrasound at 1, 3 and 6 months, and every 6 months thereafter. RESULTS: All
      tumors were completely ablated at a single session and no complications occurred.
      No residual tumor or recurrence was observed at a median followup of 11 months
      (range 4 to 20). The ablation zone was well defined on contrast enhanced imaging
      and it gradually shrank with time. CONCLUSIONS: Ultrasound guided percutaneous
      microwave ablation appears to be a safe and effective technique for small renal
      cell cancer in select patients.

PMID- 18635231
TI  - Clinical correlates of renal angiomyolipoma subtypes in 209 patients: classic,
      fat poor, tuberous sclerosis associated and epithelioid.
AB  - PURPOSE: Angiomyolipomas classically present radiographically as fat containing
      lesions but some fail to demonstrate fat content. Histologically confirmed
      angiomyolipomas uniformly follow a benign course but rare epithelioid variants of
      angiomyolipoma can recur and metastasize. We investigated the clinical,
      radiographic and histological characteristics of each angiomyolipoma subtype.
      MATERIALS AND METHODS: Pertinent data were recorded for 209 patients surgically
      treated for angiomyolipoma in 219 kidneys from 1981 to 2007. Classic and fat poor
      angiomyolipomas were classified radiographically based on the presence or absence
      of fat and classified histologically based on the presence of triphasic,
      monophasic or epithelioid histology. RESULTS: Median radiographic size was 3.2,
      4.9 and 10 cm in patients with a single angiomyolipoma (59% of patients),
      multiple angiomyolipomas and tuberous sclerosis (probable or definite),
      respectively. In these 3 groups 65%, 47% and 33% of lesions were not suspected
      radiographically (fat poor angiomyolipoma). Fat poor angiomyolipomas were more
      commonly single, smaller and in older patients. Triphasic histology was evident
      in 76% of angiomyolipomas with 16% demonstrating a predominance of 1 component
      and 8% containing epithelioid features. Despite potentially aggressive findings
      in 18% (eg presence within the perinephric fat, lymph node involvement) no
      angiomyolipoma recurred during a mean followup of 3.4 years (range 0 to 24). A
      total of 28 (13%) patients with angiomyolipoma had concomitant renal cell
      carcinoma. CONCLUSIONS: A surprisingly high number of resected angiomyolipomas
      was not suspected radiographically indicating the importance of precise
      radiographic characterization to minimize nephrectomy for fat poor
      angiomyolipoma, which should remain a research priority. In this sizeable single
      institution series no triphasic, monophasic or epithelioid angiomyolipoma
      recurred despite potentially aggressive findings in a substantial proportion of
      cases.

PMID- 18635232
TI  - Association of gadolinium based magnetic resonance imaging contrast agents and
      nephrogenic systemic fibrosis.
AB  - PURPOSE: We investigated the recently discovered association between gadolinium
      based magnetic resonance imaging contrast agents and the development of
      nephrogenic systemic fibrosis in patients with chronic kidney disease or acute
      kidney injury. MATERIALS AND METHODS: A systematic review of the PubMed database
      and publicly available patient databases was performed to characterize
      nephrogenic systemic fibrosis and its possible association with exposure to
      gadolinium based magnetic resonance imaging contrast agents. RESULTS: Data from
      case series reports, nephrogenic systemic fibrosis patient databases, nephrogenic
      systemic fibrosis case reporting to the Food and Drug Administration after
      gadolinium contrast agent exposure and retrospective case control studies suggest
      a strong association between the use of gadolinium based magnetic resonance
      imaging contrast agents and the subsequent development of nephrogenic systemic
      fibrosis in patients with renal disease. These data also suggest that the risk of
      nephrogenic systemic fibrosis depends on the degree of renal dysfunction, dose of
      contrast agent, gadolinium contrast agent stability and severity of concomitant
      illness. Thus, the occurrence of nephrogenic systemic fibrosis after gadolinium
      contrast agent exposure may vary from negligible up to 2% to 5% in select high
      risk clinical situations. CONCLUSIONS: Magnetic resonance imaging using
      gadolinium based contrast agents must be performed judiciously in patients with
      renal dysfunction, carefully weighing on a case by case basis the benefits of
      magnetic resonance imaging and the risk of nephrogenic systemic fibrosis as well
      as the disadvantages of undergoing alternative or foregoing imaging studies.

PMID- 18635233
TI  - Association between hospital and surgeon radical prostatectomy volume and patient
      outcomes: a systematic review.
AB  - PURPOSE: We examined the association between hospital and surgeon volume, and
      patient outcomes after radical prostatectomy. MATERIALS AND METHODS: Databases
      were searched from 1980 to November 2007 to identify controlled studies published
      in English. Information on study design, hospital and surgeon annual radical
      prostatectomy volume, hospital status and patient outcome rates were abstracted
      using a standardized protocol. Data were pooled with random effects models.
      RESULTS: A total of 17 original investigations reported patient outcomes in
      categories of hospital and/or surgeon annual number of radical prostatectomies,
      and met inclusion criteria. Hospitals with volumes above the mean (43 radical
      prostatectomies per year) had lower surgery related mortality (rate of difference
      0.62, 95% CI 0.47-0.81) and morbidity (rate difference -9.7%, 95% CI -15.8, 
      3.6). Teaching hospitals had an 18% (95% CI -26, -9) lower rate of surgery
      related complications. Surgeon volume was not significantly associated with
      surgery related mortality or positive surgical margins. However, the rate of late
      urinary complications was 2.4% lower (95% CI -5, -0.1) and the rate of long-term
      incontinence was 1.2% lower (95% CI -2.5, -0.1) for each 10 additional radical
      prostatectomies performed by the surgeon annually. Length of stay was lower,
      corresponding to surgeon volume. CONCLUSIONS: Higher provider volumes are
      associated with better outcomes after radical prostatectomy. Greater
      understanding of factors leading to this volume-outcome relationship, and the
      potential benefits and harms of increased regionalization is needed.

PMID- 18635234
TI  - Medical stone management: 35 years of advances.
AB  - PURPOSE: The urological community has had a vital role in the author's 35 years
      of research on the medical management of urolithiasis. The goal of this article
      is to review the progress made from the perspective of collaborating urologists
      and urological journals in which the findings were reported. MATERIALS AND
      METHODS: The author's work appeared in 94 articles in urological journals,
      including 63 in The Journal of Urology, and in 28 other journals with
      collaborating urologists. Progress on various aspects of medical management of
      stone disease was reviewed based on these articles. RESULTS: Pathophysiological
      exploration was performed by elucidating metabolic-dietary etiologies of
      hypocitraturia, separating hypercalciuria into 3 types, and linking gouty
      diathesis (uric acid stones) with obesity and insulin resistance. Physicochemical
      consequences of hypocitraturia were delineated and semi-empirical methods were
      developed to assess calcium salt saturation. Potassium-rich fruit juices differed
      from potassium-poor fruit juices and excessive salt intake increased the stone
      forming risk. Vital to diagnostic separation was a comprehensive analysis of
      urine for stone risk factors. As an example of selective treatment, potassium
      citrate was shown to be useful for controlling uric acid stones by urinary
      alkalinization as well as calcareous stones by hypercitraturia. CONCLUSIONS:
      During the last 35 years much progress has been made on the pathophysiology of
      stone formation, crystallization of stone forming salts, diagnostic separation
      and prevention of stone recurrence. The author's contribution in this effort
      would not have been possible without the active participation and support of the
      urological community.

PMID- 18635235
TI  - How many drugs for LUTS due to BPH are too many?

PMID- 18635236
TI  - A critical appraisal of preventive slings and prolapse surgery--what's a
      urologist to do?

PMID- 18635237
TI  - How do we measure hypospadias outcomes?

PMID- 18635238
TI  - RUNX3 methylation and the potential to predict the behavior of bladder cancer.

PMID- 18635239
TI  - Institutional review board approval-more red tape or a step in the right
      direction?

PMID- 18635240
TI  - An ANN application for water quality forecasting.
AB  - Rapid urban and coastal developments often witness deterioration of regional
      seawater quality. As part of the management process, it is important to assess
      the baseline characteristics of the marine environment so that sustainable
      development can be pursued. In this study, artificial neural networks (ANNs) were
      used to predict and forecast quantitative characteristics of water bodies. The
      true power and advantage of this method lie in its ability to (1) represent both
      linear and non-linear relationships and (2) learn these relationships directly
      from the data being modeled. The study focuses on Singapore coastal waters. The
      ANN model is built for quick assessment and forecasting of selected water quality
      variables at any location in the domain of interest. Respective variables
      measured at other locations serve as the input parameters. The variables of
      interest are salinity, temperature, dissolved oxygen, and chlorophyll-alpha. A
      time lag up to 2Delta(t) appeared to suffice to yield good simulation results. To
      validate the performance of the trained ANN, it was applied to an unseen data set
      from a station in the region. The results show the ANN's great potential to
      simulate water quality variables. Simulation accuracy, measured in the Nash
      Sutcliffe coefficient of efficiency (R(2)), ranged from 0.8 to 0.9 for the
      training and overfitting test data. Thus, a trained ANN model may potentially
      provide simulated values for desired locations at which measured data are
      unavailable yet required for water quality models.

PMID- 18635241
TI  - fMRI evidence for the effect of verbal complexity on lateralisation of the neural
      response associated with decoding prosodic emotion.
AB  - The pattern of intonation accompanying an utterance provides a powerful cue as to
      a speaker's emotional state of mind. Most prior lesion studies have demonstrated
      that the nodal point for decoding these prosodic emotion cues is mediated by
      unimodal auditory cortex in the right posterior lateral temporal lobe. However,
      functional neuroimaging has brought with it increasing attention to the
      equivalent left hemisphere region in this role. This study used fMRI to
      quantitatively assess the hypothesis that involvement of the left posterior
      lateral temporal lobe depended on the linguistic load or verbal complexity of the
      prosodic emotion stimuli. BOLD contrast data was acquired on a 3T scanner whilst
      16 healthy young adults identified the prosodic emotion in three conditions:
      'sentences' comprised of words, a repeated monosyllable, and a single prolonged
      syllable (asyllabic). Whole-brain analyses were performed using SPM5 and
      supplemented by posterior lateral temporal lobe region of interest (ROI)
      analyses. The whole-brain analyses appeared to show bilateral temporal lobe
      activation across the conditions, however, the ROI analyses indicated a highly
      significant decrease in activity in the left ROI as verbal complexity decreased.
      Changes in right ROI activity were not statistically significant. Our results
      indicate that the likelihood of observing a notable left temporal lobe response
      in functional neuroimaging studies of emotional prosody comprehension depends on
      the verbal complexity of the prosodic emotion stimuli. Despite the right
      hemisphere dominance underlying this task, the left hemisphere region may be co
      activated in its attempt to extract phonetic-segmental information from the
      acoustic stimuli whether or not the stimuli contain meaningful phonetic-segmental
      information.

PMID- 18635242
TI  - Lipid peroxidation in the cerebrospinal fluid of patients with
      neurocysticercosis.
AB  - The variety of symptoms observed in patients with neurocysticercosis (NCC) is
      associated with the generation of reactive species by inflammatory cells.
      Reactive species can damage the cell membrane, inducing lipid peroxidation (LP)
      and giving rise to genotoxic free radicals. In this study we investigated the
      presence of LP products in cerebrospinal fluid (CSF) and the frequency of DNA
      damage in peripheral lymphocytes from 25 patients with NCC. Patients with NCC
      showed higher LP levels compared to controls (n=7), especially patients
      presenting with severe symptoms. There was a significant correlation between LP
      and the inflammatory response (Spearman's correlation coefficient 0.75, P<0.01).
      The presence of free radicals in the central nervous system (CNS) may favour the
      development of severe clinical symptoms, even in patients under anti-inflammatory
      treatment but with a poor response. DNA damage correlated with the presence of LP
      and with symptom severity (correlation coefficient 0.30, P<0.05, and 0.54,
      P<0.01, respectively). These results demonstrate the generation of oxidative
      damage in the CNS of patients with NCC, which may be responsible for the severity
      of the symptoms. LP determination in the CSF of patients with NCC could be used
      to determine the inflammatory reaction developed.

PMID- 18635243
TI  - Cobalt chloride attenuates hypobaric hypoxia induced vascular leakage in rat
      brain: molecular mechanisms of action of cobalt chloride.
AB  - This study reports the efficacy of cobalt preconditioning in preventing hypobaric
      hypoxia induced vascular leakage (an indicator of cerebral edema) using male
      Sprague-Dawley rats as model system. Exposure of animals to hypobaric hypoxia led
      to a significant increase in vascular leakage, reactive oxygen species (ROS),
      nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels. There
      was a marked increase in Nuclear Factor kappaB (NFkappaB) DNA binding activity
      and levels of pro-inflammatory cytokines such as Monocyte chemoattractant protein
      (MCP-1), Interferon-gamma (IFN-gamma), Interleukin-1 (IL-1), and Tumor Necrosis
      Factor-alpha (TNF-alpha) and cell adhesion molecules such as Vascular Cell
      Adhesion Molecule-1 (VCAM-1), and P-selectin. Chemical preconditioning by cobalt
      for 7 days (12.5 mg Co/kg b.w., oral) significantly attenuated cerebral vascular
      leakage and the expression of inflammatory mediators induced by hypoxia.
      Administration of NFkappaB inhibitor, curcumin (50 mg/kg b.w.; i.p.) appreciably
      inhibited hypoxia induced vascular leakage indicating the involvement of NFkappaB
      in causing vascular leakage. Interestingly, cobalt when administered at 12.5 mg
      Co/kg b.w. (i.p.), 1 h before hypoxia could not prevent the vascular leakage
      indicating that cobalt per se did not have an effect on NFkappaB. The lower
      levels of NFkappaB observed in the brains of cobalt administered animals might be
      due to higher levels of antioxidant and anti-inflammatory proteins (hemeoxygenase
      1 and metallothionein). To conclude cobalt preconditioning inhibited hypobaric
      hypoxia induced cerebral vascular leakage by lowering NFkappaB DNA binding
      activity and its regulated pro-inflammatory mediators. This is contemplated to be
      mediated by cobalt induced reduction in ROS/NO and increase in HO-1 and MT.

PMID- 18635244
TI  - An ultrasound technique for monitoring the alcoholic wine fermentation.
AB  - In this paper an ultrasonic technique, usually used in non-destructive-testing
      (NDT), is applied to the monitoring of alcoholic wine fermentation. This
      technique consists in placing a test tube, containing the analyzing fluid,
      between two matched ultrasonic piezoelectric transducers, one used as transmitter
      and the other as receiver. The transmitter generates an ultrasonic wave in the
      liquid sample which is received by the receiver; the attenuation and the delay of
      the received signal in respect to the transmitted one are used to characterize
      the testing fluid. As first experiments this technique was applied to some test
      solutions of saccharose in water, ethanol in water and of both solvents in water,
      in order to evaluate the method applicability and resolution. Best results are
      obtained by the propagation velocity measurement, with a resolution less than 2%.
      The method was then applied to monitor the wine fermentation: the propagation
      velocity in the must was measured every day and the results were related to
      chemical analyses. The obtained results show that the propagation velocity has
      the same behaviour of the saccharose concentration, putting in evidence the
      possibility of monitoring the process state by measuring the ultrasound
      propagation velocity.

PMID- 18635245
TI  - Phosphorylation of human polyomavirus BK agnoprotein at Ser-11 is mediated by PKC
      and has an important regulative function.
AB  - The human polyomavirus BK (BKV) genome encodes the capsid proteins VP1 to VP3 and
      the three regulatory proteins, large and small tumor-antigen and the agnoprotein.
      Agnoprotein is a phospho-protein, but phosphorylation sites, protein kinases that
      mediate phosphorylation, and the biological importance of phosphorylation for the
      life-cycle of BK virus remain unknown. Here, we show that protein kinase C
      phosphorylates BKV agnoprotein at serine-11. Replacing serine-11 by either non
      phosphorylable alanine or phospho-mimicking aspartic acid reduced the ability of
      these mutants to propagate compared to wildtype virus. Moreover, both these
      mutants displayed altered expression of viral proteins, which resulted from
      changed transrepressive property and stability of the mutated agnoprotein. Our
      results indicate that BKV propagation is controlled by phosphorylation of the
      agnoprotein and may suggest that specific inhibition of protein kinases may be
      used as a therapeutic strategy to hamper BK virus infection.

PMID- 18635246
TI  - Aerobic biodegradation of dichloroethenes by indigenous bacteria isolated from
      contaminated sites in Africa.
AB  - The widespread use of tetrachloroethene (PCE) and trichloroethene (TCE) as dry
      cleaning solvents and degreasing agents for military and industrial applications
      has resulted in significant environmental contamination worldwide. Anaerobic
      biotransformation of PCE and TCE through reductive dechlorination frequently lead
      to the accumulation of dichloroethenes (DCEs), thus limiting the use of reductive
      dechlorination for the biotransformation of the compounds. In this study, seven
      bacteria indigenous to contaminated sites in Africa were characterized for DCE
      degradation under aerobic conditions. The specific growth rate constants of the
      bacterial isolates ranged between 0.346-0.552 d(-1) and 0.461-0.667 d(-1) in cis
      DCE and trans-DCE, respectively. Gas chromatographic analysis revealed that up to
      75% of the compounds were degraded within seven days with the degradation rate
      constants ranging between 0.167 and 0.198 d(-1). The two compounds were also
      observed to be significantly degraded, simultaneously, rather than sequentially,
      when present as a mixture. Phylogenetic analysis of the 16S rRNA gene sequences
      of the bacterial isolates revealed their identity as well as their relation to
      other environmentally-important bacteria. The observed biodegradation of DCEs may
      contribute to PCE and TCE removal at the aerobic fringe of groundwater plumes
      undergoing reductive dechlorination in contaminated sites.

PMID- 18635247
TI  - Cranial morphology of Javanese Homo erectus: new evidence for continuous
      evolution, specialization, and terminal extinction.
AB  - Our current knowledge of the evolution of Homo during the early to middle
      Pleistocene is far from complete. This is not only because of the small number of
      fossil samples available, but also due to the scarcity of standardized datasets
      which are reliable in terms of landmark identification, interobserver error, and
      other distorting factors. This study aims to accurately describe the cranial
      morphological changes of H. erectus in Java using a standardized set of
      measurements taken by the authors from 18 adult crania from Sangiran, Trinil,
      Sambungmacan, and Ngandong. The identification of some obscure landmarks was
      aided by the use of micro-CT imaging. While recent studies tend to emphasize
      evolutionary conservatism in Javanese H. erectus, our results reinforce the
      theory that chronologically later groups experienced distinct morphological
      changes in a number of cranial traits. Some of these changes, particularly those
      related to brain size expansion, are similar to those observed for the genus Homo
      as a whole, whereas others are apparently unique specializations restricted to
      Javanese H. erectus. Such morphological specializations in Java include
      previously undescribed anteroposterior lengthening of the midcranial base and an
      anterior shift of the posterior temporal muscle, which might have influenced the
      morphology of the angular torus and supramastoid sulcus. Analyses of
      morphological variation indicate that the three crania from Sambungmacan
      variously fill the morphological gap between the chronologically earlier (Bapang
      AG, Bapang Formation above the Grenzbank zone in Sangiran) and later (Ngandong)
      morphotypes of Java. At least one of the Bapang-AG crania, Sangiran 17, also
      exhibits a few characteristics which potentially indicate evolution toward the
      Ngandong condition. These strongly suggest the continuous, gradual morphological
      evolution of Javanese H. erectus from the Bapang-AG to Ngandong periods. The
      development of some unique features in later Javanese H. erectus supports the
      hypothesis that this Javanese lineage went extinct without making significant
      contributions to the ancestry of modern humans.

PMID- 18635248
TI  - Sources and properties of non-exhaust particulate matter from road traffic: a
      review.
AB  - While emissions control regulation has led to a substantial reduction in exhaust
      emissions from road traffic, currently non-exhaust emissions from road vehicles
      are unabated. These include particles from brake wear, tyre wear, road surface
      abrasion and resuspension in the wake of passing traffic. Quantification of the
      magnitude of such emissions is problematic both in the laboratory and the field
      and the latter depends heavily upon a knowledge of the physical and chemical
      properties of non-exhaust particles. This review looks at each source in turn,
      reviewing the available information on the source materials and particles derived
      from them in laboratory studies. In a final section, some of the key publications
      dealing with measurements in road tunnels and the roadside environment are
      reviewed. It is concluded that with the exception of brake dust particles which
      may be identified from their copper (Cu) and antimony (Sb) content, unequivocal
      identification of particles from other sources is likely to prove extremely
      difficult, either because of the lack of suitable tracer elements or compounds,
      or because of the interactions between sources prior to the emission process.
      Even in the case of brake dust, problems will arise in distinguishing directly
      emitted particles from those arising from resuspension of deposited brake dust
      from the road surface, or that derived from entrainment of polluted roadside
      soils, either directly or as a component of road surface dust.

PMID- 18635249
TI  - An integrated colloid fractionation approach applied to the characterisation of
      porewater uranium-humic interactions at a depleted uranium contaminated site.
AB  - Methods for the fractionation of aquatic colloids require careful application to
      ensure efficient, accurate and reproducible separations. This paper describes the
      novel combination of mild colloidal fractionation and characterisation methods,
      namely centrifugal ultrafiltration, gel electrophoresis and gel filtration along
      with spectroscopic (UV-visible) and elemental (Inductively Coupled Plasma-Optical
      Emission Spectroscopy, Inductively Coupled Plasma-Mass Spectrometry) analysis, an
      approach which produced highly consistent results, providing improved confidence
      in these methods. Application to the study of the colloidal and dissolved
      components of soil porewaters from one soil at a depleted uranium (DU)
      contaminated site revealed uranium (U) associations with both large (100 kDa-0.2
      microm) and small (3-30 kDa) humic colloids. For a nearby soil with lower organic
      matter content, however, association with large (100 kDa-0.2 microm) iron (Fe)
      aluminium (Al) colloids in addition to an association with small (3-30 kDa) humic
      colloids was observed. The integrated colloid fractionation approach presented
      herein can now be applied with confidence to investigate U and indeed other trace
      metal migration in soil and aquatic systems.

PMID- 18635250
TI  - Stretch-activated non-selective cation channel: a causal link between mechanical
      stretch and atrial natriuretic peptide secretion.
AB  - The polypeptide hormone atrial natriuretic peptide (ANP) plays vital roles in
      maintaining blood volume and arterial blood pressure. The recognition of clinical
      benefits of ANP both in healthy and diseased heart identifies ANP as a potential
      candidate for therapeutic strategy in the treatment of heart disease. ANP is
      synthesized and stored in cardiac myocytes and it is released through the
      exocytosis of ANP granules both constitutively and in response to stimuli. It is
      well known that mechanical stretch is the predominant stimulus for ANP secretion.
      However, the mechanistic link between mechanical stimuli and exocytosis of ANP
      vesicles in single atrial myocyte has not yet been demonstrated. Over the last
      decade, compelling evidence suggested that stretch-activated ion channels might
      function as mechanosensors. We showed previously that direct stretch of single
      atrial myocyte using two micro-electrodes activated a non-selective cation
      channel (SAC). So far it is not known whether activation of SAC is involved in
      stretch-induced ANP secretion. The present article aims to give an overview of
      the mechanism of mechanical stretch-stimulated ANP secretion and describes an
      innovative technique to detect ANP secretion from isolated rat atrial myocytes
      with high time-resolution. Combined with capacitance measurement and patch-clamp
      technique in conjunction with in situ ANP bioassay, we were able to demonstrate
      that SAC in rat atrial myocytes acts as a mechanosensor to transduce stretch
      signals into the ANP secretion pathway.

PMID- 18635251
TI  - In silico risk assessment for drug-induction of cardiac arrhythmia.
AB  - The main components of repolarization reserve for the ventricular action
      potential (AP) are the rapid (I(Kr)) and slow (I(Ks)) delayed outward K(+)
      currents. While many drugs block I(Kr) and cause life-threatening arrhythmias
      including torsades de pointes, the frequency of arrhythmias varies between
      different I(Kr)-blockers. Different types of block of I(Kr) cause distinct
      phenotypes of prolongation of action potential duration (APD), increase in
      transmural dispersion of repolarization (TDR) and, accordingly, occurrence of
      torsades de pointes. Therefore the assessment of a drug's proarrhythmic risk
      requires a method that provides quantitative and comprehensive comparison of the
      effects of different forms of I(Kr)-blockade upon APDs and TDR. However, most
      currently available methods are not adapted to such an extensive comparison.
      Here, we introduce I(Kr)-I(Ks) two-dimensional maps of APD and TDR as a novel
      risk-assessment method. Taking the kinetics of I(Kr)-blockade into account, APDs
      can be calculated upon a ventricular AP model which systematically alters the
      magnitudes of I(Kr) and I(Ks). The calculated APDs are then plotted on a map
      where the x axis represents the conductance of I(Kr) while the y axis represents
      that of I(Ks). TDR is simulated with models corresponding to APs in epicardial,
      midcardial and endocardial myocardium. These two-dimensional maps of APD and TDR
      successfully account for differences in the risk resulting from three distinct
      types of I(Kr)-blockade which correspond to the effects of dofetilide, quinidine
      and vesnarinone. This method may be of use to assess the arrhythmogenic risk of
      various I(Kr)-blockers.

PMID- 18635253
TI  - Clinical role of cervical cancer vaccination: when and whom to vaccinate?
AB  - The recent development of two highly effective vaccines against persistent
      infection by the 2 most important types of human papillomavirus (HPV) (16 and 18)
      and against high grade premalignant lesions (CIN2+) has opened a new scenario for
      the primary prevention of cervical cancer. The optimum target population for
      vaccination should be individually defined taking the following into account: 1)
      the efficacy of the vaccine, 2) the epidemiological context and 3) the
      vaccination programs available in each country. To achieve the maximum preventive
      benefits, the vaccine should be administered before the initiation of sexual
      relations. So, the HPV vaccine should be integrated in the school vaccination
      programs of adolescents together with other vaccines. The vaccination of sexually
      active women may considerably increase the speed with which results in the fight
      against this disease will be achieved. Developed countries will probably consider
      the vaccination of these women, although vaccination strategies and the efforts
      to reach this population will be conditioned by the resources of each country and
      by the estimations of the cost-efficacy relationship in each situation. Women
      with a previous history of premalignant cervical disease or with an abnormal
      screening test should not be excluded from the potential benefits which the
      vaccine may provide. There is no contraindication for the administration of the
      vaccine in immunosupressed women. However, it is still unknown under what
      specific circumstances of immunosuppression the immunogenicity of the vaccine may
      be affected and there are currently ongoing studies for an answer to this
      question.

PMID- 18635252
TI  - Frozen-section evaluation of cervical adenocarcinoma at time of radical
      trachelectomy: pathologic pitfalls and the application of an objective scoring
      system.
AB  - OBJECTIVE: To analyze the incidence of diagnostic discrepancy between frozen
      section and final diagnosis of the endocervical margin at time of radical
      trachelectomy and to apply an objective scoring system to non-invasive
      endocervical glandular atypia to determine its utility in distinguishing benign
      from malignant lesions. METHODS: Histologic slides from 19 cases of radical
      trachelectomy performed for invasive endocervical adenocarcinoma were evaluated
      for correlation between the frozen and permanent sections of the endocervical
      margin. An objective scoring system for grading non-invasive endocervical
      glandular lesions proposed by Ioffe et al. was also applied to the frozen and
      permanent section slides and compared to the final diagnosis. RESULTS: There was
      84% concordance between the frozen-section and final diagnosis using histology
      alone, vs. 95% concordance using the Ioffe scoring system. One trachelectomy was
      converted to completion hysterectomy for what was presumed to be adenocarcinoma
      in situ at the margin, which in retrospect, was a benign lesion and was correctly
      classified using the Ioffe system. Most of the discrepancies were due to
      misinterpretation of tubal metaplasia, tubo-endometrioid metaplasia, and atypical
      tubal metaplasia as adenocarcinoma in situ. CONCLUSION: Benign mimics of
      endocervical adenocarcinoma in situ can be difficult to distinguish from
      malignant lesions, especially during frozen-section evaluation of the
      trachelectomy. Correctly diagnosing the margin status intraoperatively has great
      clinical impact and the application of an objective scoring system, like that
      proposed by Ioffe et al., can increase diagnostic accuracy when applied to frozen
      section slides and better correlates with final diagnosis when compared to
      histology alone.

PMID- 18635254
TI  - fMR-adaptation and the bilingual brain.
AB  - fMR-Adaptation, where a pair of identical stimuli elicits a smaller neural
      response than a pair of dissimilar stimuli has been extensively used to study
      object identification and classification as well as memory. Thus far this
      technique has found limited application in evaluating brain areas sensitive to
      meaning, language and control of language production. These studies are reviewed
      together with suggestions as to how varying inter-stimulus repetition lag,
      dimension of interest and evaluating inter-individual differences may shed new
      light on how different languages are acquired and represented in the brain.

PMID- 18635255
TI  - Influence of study design on the impact of bleaching agents on dental enamel
      microhardness: a review.
AB  - OBJECTIVE: Numerous studies investigated the impact of bleaching procedures on
      enamel microhardness. The outcomes of these studies reveal inconsistencies
      regarding the fact whether a microhardness reduction due to bleaching occurs or
      not. Aim of the present review was to summarize the existing literature of
      external bleaching therapies, which used microhardness tests for evaluation of
      possible effects on enamel and to weigh up different parameters of the study
      designs with respect to the outcome of these studies. METHODS: The data from
      original scientific full papers listed in PubMed or ISI Web of Science (search
      term: enamel and (bleaching or peroxide) and (hardness or microhardness or Knoop
      or Vickers)) and received by additional hand-search meeting the inclusion
      criteria were included in the review. Influences of different parameters on the
      outcome of the bleaching treatments were analyzed with the Fisher's-exact-test.
      RESULTS: A total of 55 studies were identified with 166 hardness measurements
      conducted directly after bleaching and 69 measurements performed after a post
      treatment episode. Directly after bleaching, 84 (51%) treatments showed
      microhardness reduction compared to baseline, whereas 82 (49%) did not yield
      microhardness reduction. After the post-treatment episode, 20 (29%) treatments
      showed hardness reduction and 49 (71%) did not. A significant higher number of
      bleaching treatments resulting in enamel microhardness reduction were observed,
      when artificial instead of human saliva was used for storage of the enamel
      samples in the intervals between the bleaching applications and when no
      fluoridation measures were applied during or after the bleaching phase.
      SIGNIFICANCE: The review shows that in those studies, which simulated the
      intraoral conditions as closely as possible, the risk of enamel microhardness
      decrease due to bleaching treatments seems to be reduced. Nevertheless more in
      situ- and in vivo-studies are needed to verify this observation.

PMID- 18635256
TI  - Comparison of methotrexate monotherapy with a combination of methotrexate and
      etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a
      randomised, double-blind, parallel treatment trial.
AB  - BACKGROUND: Remission and radiographic non-progression are goals in the treatment
      of early rheumatoid arthritis. The aim of the combination of methotrexate and
      etanercept in active early rheumatoid arthritis (COMET) trial is to compare
      remission and radiographic non-progression in patients treated with methotrexate
      monotherapy or with methotrexate plus etanercept. METHODS: 542 outpatients who
      were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis
      for 3-24 months were randomly assigned to receive either methotrexate alone
      titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or
      methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints
      at 52 weeks were remission measured with the disease activity score in 28 joints
      (DAS28) and radiographic non-progression measured with modified total Sharp
      score. Treatment was allocated with a computerised randomisation and enrolment
      system, which masked both participants and carers. Analysis was done by modified
      intention to treat with last observation carried forward for missing data. This
      study is registered with ClinicalTrials.gov, number NCT00195494). FINDINGS: 274
      participants were randomly assigned to receive combined treatment and 268
      methotrexate alone. 132 of 265 (50%, 95% CI 44-56%) patients who took combined
      treatment and were available for assessment achieved clinical remission compared
      with 73 of 263 (28%, 23-33%) taking methotrexate alone (effect difference 22.05%,
      95%CI 13.96-30.15%, p<0.0001). 487 evaluable patients had severe disease
      (DAS28>5.1). 196 of 246 (80%, 75-85%) and 135 of 230 (59%, 53-65%), respectively,
      achieved radiographic non-progression (20.98%, 12.97-29.09%, p<0.0001). Serious
      adverse events were similar between groups. INTERPRETATION: Both clinical
      remission and radiographic non-progression are achievable goals in patients with
      early severe rheumatoid arthritis within 1 year of combined treatment with
      etanercept plus methotrexate. FUNDING: Wyeth Research.

PMID- 18635257
TI  - COMET's path, and the new biologicals in rheumatoid arthritis.

PMID- 18635258
TI  - Human clinical experience with adipose precursor cells seeded on hyaluronic acid
      based spongy scaffolds.
AB  - Histioconductive approaches to soft-tissue defects use scaffolds seeded with
      lineage- and tissue-specific progenitors to generate tissue which should reside
      in equilibrium with adjacent tissue. Scaffolds guide histiogenesis by ensuring
      cell-cell and cell-matrix interactions. Hyaluronic acid-based (HA) preadipocyte
      seeded scaffolds were evaluated for their adipo-conductive potential and efficacy
      in humans. Preadipocytes were isolated from lipoaspirate material and seeded on
      HA scaffolds. The cellular bio-hybrid (ADIPOGRAFT) and an acellular control
      scaffold (HYAFF11) were implanted subcutaneously. At specific time points (2, 8
      and 16 weeks) explants were analyzed histopathologically with
      immunohistochemistry. No adverse tissue effects occurred. Volume loss and
      consistent degradation of the HYAFF11 scaffolds compared to the ADIPOGRAFT group
      indicated progressive tissue integration. No consistent histological differences
      between both groups were observed. By 8 weeks all void spaces within the
      scaffolds were filled with cells with pronounced matrix deposition in the
      ADIPOGRAFT bio-hybrids. Here we show that HA scaffolds were stable cell carriers
      and had the potential to generate volume-retaining tissue. However, no adipogenic
      differentiation was observed within the preadipocyte-seeded scaffolds.

PMID- 18635259
TI  - Microfabricated silicon nitride membranes for hepatocyte sandwich culture.
AB  - We have developed a hepatocyte sandwich culture with improved mass transport
      properties based on ultra-thin microfabricated porous silicon nitride (Si(3)N(4))
      membranes. The dimensions and uniformity of the membrane pores can be
      configurable, which confers more control over the mass transport. Instead of
      collagen gels used in conventional sandwich culture, we utilized galactose
      ligands immobilized on the Si(3)N(4) membranes to support hepatocyte attachment
      and function in the sandwich culture. Diffusion studies using FITC-dextrans
      confirmed that mass transport of the microfabricated Si(3)N(4) membrane based
      sandwich was significantly better than conventional collagen gel sandwich and can
      be configured by varying the porosity of the Si(3)N(4) membrane. Hepatocytes
      cultured in the microfabricated Si(3)N(4) membrane based sandwich culture
      exhibited earlier apical repolarization and biliary excretion, improved
      differentiated functions and enhanced drug sensitivity compared to hepatocytes
      cultured in a collagen gel sandwich. The Si(3)N(4) membrane based sandwich
      culture allows for a systematic optimization of the mass transport properties of
      hepatocyte culture by changing the pore size and inter-pore distance. This will
      enable more effective drug testing applications where optimal mass transport is
      required for hepatocyte function maintenance and drug accessibility.

PMID- 18635260
TI  - 3D imaging of tissue integration with porous biomaterials.
AB  - Porous biomaterials designed to support cellular infiltration and tissue
      formation play a critical role in implant fixation and engineered tissue repair.
      The purpose of this Leading Opinion Paper is to advocate the use of high
      resolution 3D imaging techniques as a tool to quantify extracellular matrix
      formation and vascular ingrowth within porous biomaterials and objectively
      compare different strategies for functional tissue regeneration. An initial over
      reliance on qualitative evaluation methods may have contributed to the false
      perception that developing effective tissue engineering technologies would be
      relatively straightforward. Moreover, the lack of comparative studies with
      quantitative metrics in challenging pre-clinical models has made it difficult to
      determine which of the many available strategies to invest in or use clinically
      for companies and clinicians, respectively. This paper will specifically
      illustrate the use of microcomputed tomography (micro-CT) imaging with and
      without contrast agents to nondestructively quantify the formation of bone,
      cartilage, and vasculature within porous biomaterials.

PMID- 18635261
TI  - Mechanical deformation of ventricular myocytes modulates both TRPC6 and Kir2.3
      channels.
AB  - Cardiomyocytes respond to mechanical stretch with an increase [Ca2+]i. Here, we
      analyzed which ion channels could mediate this effect. Murine ventricular
      myocytes were attached to a glass coverslip and a cell-attached glass stylus
      sheared the upper cell part versus the attached cell bottom. At negative clamp
      potentials, stretch induced inward currents that increased with the extent of
      stretch and reversed within 2 min after relaxation from stretch. Stretch
      activated a nearly voltage-independent GsMTx-4-sensitive non-selective cation
      conductance Gns, antibodies against TRPC6 prevented Gns activation. In addition,
      stretch deactivated a Cs+-sensitive inwardly rectifying potassium conductance
      GK1, antibodies against Kir2.3 inhibited this effect. Immunolabeling localized
      TRPC6 and Kir2.3 in T-tubular membranes, and stretch-induced changes in membrane
      currents were absent in cells whose T-tubules had been removed. In absence of
      stretch, we could activate Gns and deactivate GK1 by 1-oleoyl-2-acetyl-sn
      glycerol (OAG) and other amphipaths. We interpret that the function of TRPC6 and
      Kir2.3 channels is controlled by both tension and curvature of the surrounding
      lipid bilayer that are changed by incorporation of amphipaths. Stretch-activation
      of TRPC6 channels may increase Ca2+ influx directly and indirectly, by membrane
      depolarization (activation of voltage-gated Ca2+ channels) and by elevated [Na+]i
      (augmented Na+,Ca2+-exchange).

PMID- 18635262
TI  - The archeology of substance P.

PMID- 18635263
TI  - Spatial and temporal variations of microcystins in hepatopancreas of a freshwater
      snail from Lake Taihu.
AB  - In this paper, spatial and temporal variations of three common microcystins (MC
      RR, MC-YR, and MC-LR) in the hepatopancreas of a freshwater snail (Bellamya
      aeruginosa) were studied monthly in two bays of Lake Taihu. Microcystins (MCs)
      concentration in hepatopancreas was quantified by liquid chromatography-mass
      spectrometry (LC-MS). The MCs concentrations in hepatopancreas were higher at
      Site 1 than those at other sites, which was in agreement with the changes of
      intracellular MCs concentrations in the water column. There was a significant
      correlation between MCs concentrations in the hepatopancreas and that in the
      seston, suggesting that spatial variances of MCs concentrations in hepatopancreas
      among the five sites were due to spatial changes of toxic Microcystis cells in
      the water column. PCCA indicates that in addition to Microcystis, other factors
      (e.g., water temperature) also substantially affected the accumulation of MCs in
      hepatopancreas of the snail.

PMID- 18635264
TI  - Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the
      rat cerebellum.
AB  - There is now strong evidence for non-immune or inflammatory functions of
      complement, notably in the central nervous system. In particular, it has been
      recently reported that the anaphylatoxin receptors C3aR and C5aR are transiently
      expressed in the cerebellar cortex of newborn rat, suggesting that anaphylatoxins
      are involved in the histogenesis of the cerebellum. In the present study, we have
      investigated the effects of C3aR and C5aR agonists and antagonists on the
      development of the cerebellum of 11-12-day-old rats in vivo and in vitro. Sub
      dural injection of C3aR and C5aR agonists at the surface of the cerebellum
      transiently modified the thickness of the cortical layers. The C5aR agonist
      provoked an enlargement of the external granule cell layer (EGL) that was due to
      increased proliferation of immature granule neurons. Conversely, the C3aR agonist
      decreased the thickness of the EGL and increased the thickness of the internal
      granule cell layer (IGL), suggesting that C3a accelerates the migration process
      of granule cells from the EGL to the IGL. Video-microscopy examination of
      cultured granule neurons confirmed the role of C3aR in cell motility. These
      results provide clear evidence for the involvement of anaphylatoxin receptors in
      the histogenesis of the cerebellar cortex.

PMID- 18635265
TI  - Substitution of strictly conserved Y111 in catalase-peroxidases: Impact of remote
      interdomain contacts on active site structure and catalytic performance.
AB  - Catalase-peroxidase function is strictly dependent on a gene-duplicated C
      terminal domain. This domain no longer has a functioning active site, but from 25
      to 30A away it is essential for preventing the coordination of an active site
      base (His106) to the heme. The mechanisms by which this distant structure
      supports active site function have not yet been elucidated. Tyr111 is a strictly
      conserved member of an interdomain H-bonding network that supports the loop
      connecting the N-terminal B (bearing His106) and C helices. Spectroscopic
      evaluation of the Tyr111Ala variant of KatG showed a substantial increase in hexa
      coordinate low-spin heme, giving it the appearance of a transition between the
      wild type (primarily high-spin) and the N-terminal domain alone (pure low-spin).
      Concomitant with the spectral changes was decreased activity compared to the wild
      type enzyme, suggesting that Tyr111 does have a role in preventing His106
      coordination. Substitution of Tyr111 diminishes catalase activity more
      substantially than peroxidase activity. Such an effect cannot be explained by
      His106 coordination alone, suggesting that these interdomain interactions may
      help tune the catalase-peroxidase active site for bifunctionality.

PMID- 18635266
TI  - Use of a Pan-Vbeta primer permits the amplification and sequencing of TCRbeta
      chains expressed by bovine T-cell clones following a single semi-nested PCR
      reaction.
AB  - We report in this study the design and validation of a Pan-Vbeta primer that in
      combination with Cbeta-specific primers enables the amplification, in a single
      semi-nested PCR, of TCRbeta chains expressed by bovine T-cell clones irrespective
      of the expressed Vbeta sequence. Using the Pan-Vbeta primer we examined the
      TCRbeta chains expressed by 16 Theileria parva-specific clones that had not been
      previously analysed. TCRbeta chain sequence was obtained from 15 of the clones
      following direct sequencing of the PCR product, whilst the other clone appeared
      to express 2 different TCRbeta chains which were characterised following sub
      cloning of the PCR product. We have also successfully used the Pan-Vbeta primer
      to amplify the TCRbeta chains expressed by 19 T-cell clones, on which previous
      analysis using Vbeta-subfamily-specific primers had failed to do. Sequencing of
      these TCRbeta chains has identified members of 2 novel bovine Vbeta subfamilies
      Vbeta5 and VbetaX. This method offers a simple and rapid method of analyzing the
      TCRbeta chains of bovine T-cell clones that has many potential applications in
      the investigation of bovine T-cell responses.

PMID- 18635267
TI  - Porcine IgE in the context of experimental food allergy: purification and isotype
      specific antibodies.
AB  - Measurement of allergen-specific immunoglobulin E (IgE) is a common practice in
      the investigation of allergy. It has not been possible to measure porcine IgE due
      to unavailability of anti-porcine IgE. This study was undertaken to purify and
      characterize porcine IgE from sera of allergic pigs, identify heterologous anti
      IgE reactive with pig IgE and to use purified heavy (H) chain of porcine IgE to
      generate rabbit anti-IgE. A four-step process for the purification of porcine IgE
      is reported using ammonium sulphate precipitation, Protein G affinity
      chromatography, DEAE cellulose anion-exchange chromatography and sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) to obtain IgE H chain. The
      resultant IgE was evaluated for purity using SDS-PAGE and immunoreactivity was
      detected by Prausnitz-Kustner (PK) tests and passive cutaneous anaphylaxis with
      the allergen, crude peanut extract, used to induce experimental allergy. Cross
      reactivity with anti-mouse and anti-human IgE antibodies were confirmed in
      western blot and enzyme-linked immunosorbent assays (ELISA). The H chain of IgE
      was excised from SDS-PAGE gels and used to develop rabbit anti-porcine IgE
      antisera. Antiserum obtained from rabbits immunized with porcine IgE, as well as
      heterologous murine and human-specific anti-IgE, induced reverse cutaneous
      anaphylaxis in pig skin and detected allergen-specific IgE in ELISA but did not
      react with IgG H chain in western blots. These results confirm allergy-associated
      bioactivity of porcine IgE and describe both homologous and heterologous anti-pig
      IgE suitable for use in allergen-specific and other assays. This will enhance
      utility of pig allergy models and provide an additional measure of type-2 immune
      response in pigs.

PMID- 18635268
TI  - Phosphorylcholine-coated antibiotic tympanostomy tubes: are post-tube placement
      complications reduced?
AB  - OBJECTIVE: To determine if a phosphorylcholine (PC) antibacterial coating on
      standard Armstrong beveled tympanostomy tubes (TT) reduced the incidence of post
      tube placement complications. METHODS: A prospective cohort aged 8-51 months
      received bilateral TTs for otitis media with effusion between July 2002 and
      February 2004 at a tertiary care pediatric hospital. Seventy children were
      randomized to receive a PC-coated TT in one ear and an uncoated TT in the other.
      Otologic examinations at prescribed intervals over two years post-operatively
      ascertained the status of sequelae. We analyzed the incidence of TT
      complications: otorrhea, premature extrusion, persistent tympanic membrane
      perforations, granulation tissue, and ventilation tube lumen obstruction.
      RESULTS: There was no statistical difference in the incidence of any of these
      sequelae between standard and PC-coated tympanostomy tubes (p>0.05) during the 24
      month-follow-up period. Results after 13 months of follow-up may have been
      affected by patients lost to follow-up and therefore a smaller sample size as the
      study continued. CONCLUSIONS: This study found that there is no statistically
      significant difference in the incidence of complications between uncoated and PC
      coated fluoroplastic Armstrong beveled TTs.

PMID- 18635269
TI  - Tonsillotomy in the treatment of obstructive sleep apnea syndrome in children:
      polysomnographic results.
AB  - INTRODUCTION: The therapy of choice in the treatment of pediatric obstructive
      sleep apnea syndrome (OSAS) consists of tonsillectomy or tonsillotomy combined
      with adenoidectomy. While tonsillectomy unfortunately has a notable risk of
      secondary hemorrhage and postoperative pain, tonsillotomy is safer and less
      painful for children. The effect of both surgical methods on symptoms of OSAS
      seems to be equal, but up to now postoperative polysomnographic data for children
      treated by tonsillotomy are missing. MATERIALS AND METHODS: Twenty children aged
      2-9 years (mean age: 4.1+/-2.0 years) with OSAS diagnosed by full-night
      polysomnography were included in the study. OSAS was defined as an apnea-hypopnea
      index (AHI) of 5 or more with minimum oxygen saturation (SaO(2) min) of less than
      90%. Exclusion criteria were obesity, craniofacial abnormalities or other
      pulmonary, cardiac or metabolic diseases as well as a history of recurrent
      tonsillitis. All children were treated by CO(2) laser tonsillotomy and
      adenoidectomy. Three to 12 months (mean: 7.7 months) after the procedure a
      control-polysomnography was performed in all children. RESULTS: No statistically
      significant changes were seen in the pre- and postoperative distribution of sleep
      stages, sleep efficacy and total sleep time. The AHI decreased from 14.9+/-8.7 to
      1.1+/-1.6 (p<0.001), SaO(2) min increased from 71.1+/-11.1% to 91.2+/-3.5%
      (p<0.001). Thus, all children were cured by the operation. DISCUSSION: These
      polysomnographic data show that CO(2) laser tonsillotomy in combination with
      adenoidectomy is highly effective in the treatment of pediatric OSAS and should
      be preferred over tonsillectomy because of less postoperative pain and a lower
      risk of postoperative bleeding.

PMID- 18635270
TI  - Endovascular embolization of a hemorrhagic jugular bulb diverticulum.
AB  - A jugular bulb diverticulum (JBD) is considered to be a rare venous anomaly. In
      exceptional cases it extends into the middle ear cavity with no bony covering,
      and slight oozing to massive bleeding might be encountered during routine middle
      ear surgical procedures. We report a case of massive bleeding from a dehiscent
      jugular bulb diverticulum that appeared during myringotomy and was successfully
      managed by endovascular embolization. This report emphasizes the value of
      interventional neuroradiology in otosurgical cases in which preoperative control
      of blood vessels or vascular malformations is crucial to avoid severe
      complications.

PMID- 18635271
TI  - Education and training of young people who grew up with cochlear implants.
AB  - AIMS: We want to provide new qualitative and quantitative data on the long-term
      impact of cochlear implantation (CI) on educational placement, vocational
      outcomes and employment status of hearing-impaired adolescents and young adults.
      METHODS: 52 cochlear implant users (age: 12-21 years) and a control group of 155
      normal-hearing peers participated in structured interviews on their educational
      level, achievement, satisfaction with their vocational placement and
      correspondence between career aspiration and actual occupation. RESULTS: The
      educational level of CI-using pupils did not differ from the Austrian population.
      More than 80% of school-aged children attended mainstream schools. The
      educational level was positively correlated to the educational level of the
      father and performance on numbers in an auditory speech test. Nevertheless,
      parents of pupils with cochlear implants rated the future career chances of their
      children significantly less optimistic than parents of normal-hearing peers. More
      than 60% of secondary post-graduates (alumni) completed their education in
      mainstream schools, two studied at university. 12 out of 13 participants, who
      required work, were employed, 75% of them with regular contracts. Although all CI
      users reported high satisfaction with their work, the correspondence between
      career aspiration and actual occupation was significantly lower for CI-users
      compared to normal-hearing peers. CONCLUSION: The majority of CI-users in our
      study group was well integrated into the hearing world, concerning their
      schooling and post-graduate development. However their career perspectives are
      still not satisfying.

PMID- 18635272
TI  - Erosion of the incus in pediatric posterior tympanic membrane retraction pockets
      without cholesteatoma.
AB  - OBJECTIVE: To determine the incidence of erosion of the incus in pediatric
      patients operated for atelectasis with postero-superior retraction pockets and
      incudopexy. Associated hearing loss was determined and a comparison was made
      between the patients with and without incus erosion. METHODS: Observational study
      of patients seen and operated at the Sophia Children's Hospital in Rotterdam
      between 2002 and 2005. All patients who had undergone surgery for posterior
      retraction pockets with preoperative evidence of fixation of the tympanic
      membrane to the incudo-stapedial complex were identified for the study. Patients
      with evidence of cholesteatoma (epithelial debris within the pockets) were
      excluded from the study. Pre- and postoperative air and bone conduction
      thresholds and air-bone gaps were calculated using the four-tone pure-tone
      average for bone- and air conduction. RESULTS: In this study of 46 ears with
      posterior retractions adherent to the incus, 30% were found to have some degree
      of erosion of the incus associated with incudopexy. In the group with incudopexy
      without erosion the preoperative and postoperative air-bone gaps were 10.0+/-9.8
      and 5.9+/-8.3dB respectively. The pre-and postoperative air-bone gaps in the
      incus erosion group were 20.1+/-13.3 and 13.8+/-9.1dB respectively. The
      audiological differences between the erosion group and the non-erosion group and
      between pre- and postoperative air-bone gaps were statistically significant.
      CONCLUSION: In this group of children with posterior retraction pockets adherent
      to the incus, we found at surgery a high incidence of erosion of the incus. The
      audiometric data confirms that early surgery does not adversely affect the
      postoperative hearing where there is no erosion of the incus, and likewise the
      improvement in air-bone gap postoperatively was statistically significant in the
      erosion group. On the basis of these findings we suggest that watchful waiting
      may not be the best strategy in pediatric atelectasis once the tympanic membrane
      has become adherent to the ossicular chain.

PMID- 18635273
TI  - Circumstances surrounding falls in patients with dementia in a psychogeriatric
      ward.
AB  - People with dementia have an increased risk of falling. Predisposing factors
      explain only a small part of the variation in falls among people with dementia.
      The purpose of this study was to explore circumstances that are hazardous
      regarding falls among people with dementia at a psychogeriatric ward. The study
      comprised 191 participants of whom seventy-five fell a total of 229 times.
      Prospective data were collected on falls. Hazardous circumstances were calculated
      in two ways. Firstly possible differences between day/night falls and women/men
      falls were calculated based on the 229 falls. Secondly time to first fall was
      used to estimate hazardous circumstances and was based on 75 falls. This study
      shows a fall rate that was equally high during the night and the day. The
      proportion of diurnal rhythm disturbances and activity disturbances was higher
      for falls at night than for falls during the day. Circumstances associated with
      an increased risk of falls, as shown by a short time to first fall, were anxiety,
      darkness, not wearing any shoes and, for women, urinary tract infection. All of
      these are circumstances that should be considered in future fall-related research
      among people with dementia.

PMID- 18635274
TI  - Sudden cardiac death caused by native aortic valve thrombosis in an adult patient
      with a complex congenital cyanotic heart disease.
AB  - Cyanotic congenital heart disease is associated with an increased risk of
      thromboembolism. We describe the case of sudden cardiac death caused by native
      aortic valve thrombosis in adult cyanotic patient. Such embolic complication was
      not previously described in cyanotic patient. It is also the first report of
      sudden cardiac death as an initial presentation of the native aortic valve
      thrombosis. Cyanotic congenital heart disease (CCHD) is associated with an
      increased risk of thromboembolism due to different haemathologic abnormalities
      associated with hypoxemia and secondary polycythemia [H. Kajimoto, M. Nakazawa,
      K. Murasaki, et al. Increased thrombogenesity in patients with cyanotic
      congenital heart disease. Circ J Jun 2007;71(6):948-953]. Cerebrovascular events,
      venous and arterial thrombosis have been described in patients with CCHD [N.
      Ammash, C.A. Warnes. Cerebrovascular events in adult patients with cyanotic
      congenital heart disease. J Am Coll Cardiol Sep 1996;28(3):768-772]. We present a
      case of the native aortic valve thrombosis in an adult patient with a complex
      cyanotic congenital heart lesion which led to sudden death.

PMID- 18635275
TI  - The exercise training effects of skeletal muscle strength and muscle volume to
      improve functional capacity in patients with myocardial infarction.
AB  - BACKGROUND: No previous studies have fully investigated the exercise training
      effect on the skeletal muscle strength and volume to improve the exercise
      capacity in patients with myocardial infarction (MI). The present study was
      performed based on a hypothesis that the relationship between exercise capacity,
      skeletal muscle strength and volume might be changed by the amount of skeletal
      muscle volume in MI patients up to 3 months after the onset. METHODS: Seventy
      patients with MI underwent symptom-limited cardiopulmonary exercise testing using
      a treadmill. The lower limb muscle volume (MV) was evaluated according to
      electrical impedance analysis and the maximal knee extension strength (Peak
      torque: PT) was measured by a Biodex. All patients participated in 12-week
      exercise training program. The subjects were divided into 2 groups on the basis
      of MV: Group H, MV>==22 kg; Group L, MV<22 kg. Delta values were calculated as
      follows: the value at 3 months minus the value at 1 month. RESULTS: A positive
      and significant correlation was observed between the delta PT and delta peak
      VO(2) (r=0.50, p<0.005) only in the L group. No significant correlation was
      observed between the delta peak VO(2) and the delta lower limb MV or between the
      delta lower limb MV and the delta PT in the 2 groups. CONCLUSIONS: Cardiac
      rehabilitation program combined with resistance and aerobic training improved
      exercise capacity and increased not the skeletal muscle volume but the skeletal
      muscle strength in patients with MI in their recovery phase. It was presumed that
      the improvement of exercise capacity was determined by the skeletal muscle
      strength not by the muscle volume especially in MI patients with low muscle
      volume.

PMID- 18635277
TI  - The bluetongue outbreak in North-West Europe: the outcome from the
      epidemiological investigation coordinated by the European Food Safety Authorities
      (EFSA).

PMID- 18635276
TI  - A novel index combining diastolic and systolic Tissue Doppler parameters for the
      non-invasive assessment of left ventricular end-diastolic pressure.
AB  - BACKGROUND: Early diastolic transmitral velocity (E)/early mitral annular
      diastolic velocity (Ea) ratio has been proposed as the best Doppler predictor for
      evaluating left ventricular (LV) filling pressure. PURPOSE: To evaluate the
      relationship between a novel echocardiographic index, E/(EaxSa), and left
      ventricular end-diastolic pressure (LVEDP); Sa is the peak systolic mitral
      annular velocity. We measured this index at different sites of the mitral annulus
      and compared it with other Tissue Doppler parameters. METHODS: Echocardiography
      was performed simultaneously with left heart catheterization in 110 consecutive
      patients in sinus rhythm. E, Sa, Ea and Aa (late mitral annular diastolic
      velocity) were determined at medial and lateral site, and average values
      obtained. E/Ea and E/(EaxSa) were calculated (medial, lateral, average). LVEDP
      was measured with invasively fluid-filled catheter. RESULTS: We demonstrated
      significant correlations between LVEDP and E/(EaxSa)(lateral) (r=0.78, p<0.0001),
      E/Ea(average) (r=0.70, p<0.0001), E/Ea(lateral) (r=0.66, p<0.0001), E/Ea(medial)
      (r=0.60, p<0.0001) and E/(EaxSa)(medial) (r=0.60, p<0.0001). E/(EaxSa)(average)
      had the strongest correlation with LVEDP (r=0.80, p<0.0001). An
      E/(EaxSa)(average) cut-off of 1.6 had 86% sensitivity and 85% specificity for
      detecting LVEDP>15 mmHg. Weaker correlations were found for Sa, Ea and Aa.
      E/(EaxSa)(average) was the best parameter to assess LVEDP in patients with normal
      LV ejection fraction (LVEF>or=50%) (r=0.83, p<0.0001), depressed LVEF (r=0.76,
      p<0.0001), regional dysfunction (r=0.81, p<0.0001), or E/Ea(average) between 8
      and 15 (r=0.67, p<0.0001). CONCLUSIONS: E/(EaxSa)(average) was the best predictor
      of LVEDP in sinus rhythm patients, regardless of LVEF, particularly in those with
      E/Ea(average) between 8 and 15 and in those with regional dysfunction.

PMID- 18635278
TI  - The effect of adolescent virginity status on psychological well-being.
AB  - Although previous research has found that sexually active teens are more likely
      to suffer from depression, it is not clear whether this association is causal or
      spurious in nature. This study uses data from the National Longitudinal Study of
      Adolescent Health to examine whether virginity status affects self-esteem and
      depression. For males, fixed effects and instrumental variables (IV) estimates
      provide little evidence that sex is causally related to psychological well-being.
      In contrast, IV estimates indicate that sexually active female adolescents are at
      increased risk of exhibiting the symptoms of depression relative to their
      counterparts who are not sexually active. Comparing the psychological well-being
      of females who used contraception at last intercourse with that of virgins
      suggests that these effects may be ameliorated, but not eliminated, by
      contraceptive use.

PMID- 18635279
TI  - Biomechanics of the continuity and speed change during one revolution of the
      Fouette turn.
AB  - The purpose of this study was to investigate the biomechanics of the continuity
      and speed change of the Fouette turn. This turn is one of the turns performed on
      one leg in classical ballet and is unique in terms of its continuity and change
      in rotational speed of the torso during one revolution of the turn. We filmed the
      turn as performed by seven experienced female ballet dancers in a clockwise
      direction on a force plate using three high speed cine cameras. In a 3D motion
      analysis of the turn, we found that the dancers mainly controlled the rotational
      speed by swinging the free or gesture leg laterally through torque exertion at
      the hip joint of the leg in clockwise and then counterclockwise directions, and
      that they supplied an angular impulse mainly to the gesture leg during the swing
      when flexing the supporting leg and keeping their foot flat on the plate. This
      supply of momentum enabled them to continue the turn compensating for the loss of
      the momentum of the body brought about in a rapid rotation phase when they were
      standing on tiptoe touching the foot of the gesture leg on the knee of the
      supporting leg.

PMID- 18635280
TI  - Evaluation of the psychometric properties of the developmental coordination
      disorder questionnaire for parents (DCD-Q): results from a community based study
      of school-aged children.
AB  - In this study, we examine several key psychometric properties (reliability,
      construct validity, concurrent validity) of the Developmental Coordination
      Disorder Questionnaire (DCD-Q) using a large, school-based sample of children
      (n=523) and their parents. Children completed the Children's Self-perceptions of
      Adequacy in and Predilection toward Physical Activity (CSAPPA) and parents
      completed the DCD-Q. The internal reliability of the DCD-Q was high for both the
      full scale and the subscales. Confirmatory factor analysis established that the
      scale was multifactorial, but the fit of the hypothesized factor structure was
      poor. Finally, moderate correlations were observed between the CSAPPA and the DCD
      Q, with the strongest correlation found between the "perceived adequacy" subscale
      of the CSAPPA and "control during movement" subscale of the DCD-Q. Implications
      for screening and further research are discussed in relation to both instruments.

PMID- 18635281
TI  - Characterization of EprA, a major extracellular protein of Oenococcus oeni with
      protease activity.
AB  - Extracellular proteins from Oenococcus oeni, a wine-making bacterium, were
      isolated during growth on media differing by their nitrogen content. Analysis by
      two-dimensional electrophoresis revealed a low number of protein signals. Among
      the main spots, one signal corresponded to a single protein, which contained a
      lysine repeat domain characteristic of cell-wall hydrolases. We demonstrated that
      this major protein, named EprA, was able to hydrolyse several proteins. The
      heterologous production of this protein in Escherichia coli confirmed the
      protease activity of EprA. With a MW of 21.3 kDa and a pI of 5.3, EprA presents
      optimal activity at pH 7.0 and 45 degrees C. This O. oeni protease differs from
      all lactic acid bacteria proteases so far identified, and thus this bacterium
      possesses at least three proteases for wine protein hydrolysis.

PMID- 18635282
TI  - Comparative analysis of CRISPR loci in lactic acid bacteria genomes.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) are
      hypervariable loci widely distributed in bacteria and archaea, that provide
      acquired immunity against foreign genetic elements. Here, we investigate the
      occurrence of CRISPR loci in the genomes of lactic acid bacteria (LAB), including
      members of the Firmicutes and Actinobacteria phyla. A total of 102 complete and
      draft genomes across 11 genera were studied and 66 CRISPR loci were identified in
      26 species. We provide a comparative analysis of the CRISPR/cas content and
      diversity across LAB genera and species for 37 sets of CRISPR loci. We analyzed
      CRISPR repeats, CRISPR spacers, leader sequences, and cas gene content, sequences
      and architecture. Interestingly, multiple CRISPR families were identified within
      Bifidobacterium, Lactobacillus and Streptococcus, and similar CRISPR loci were
      found in distant organisms. Overall, eight distinct CRISPR families were
      identified consistently across CRISPR repeats, cas gene content and architecture,
      and sequences of the universal cas1 gene. Since the clustering of the CRISPR
      families does not correlate with the classical phylogenetic tree, we hypothesize
      that CRISPR loci have been subjected to horizontal gene transfer and further
      evolved independently in select lineages, in part due to selective pressure
      resulting from phage predation. Globally, we provide additional insights into the
      origin and evolution of CRISPR loci and discuss their contribution to microbial
      adaptation.

PMID- 18635283
TI  - Hydrolysis of amorphous and crystalline cellulose by heterologously produced
      cellulases of Melanocarpus albomyces.
AB  - Three thermostable neutral cellulases from Melanocarpus albomyces, a 20-kDa
      endoglucanase (Cel45A), a 50-kDa endoglucanase (Cel7A), and a 50-kDa
      cellobiohydrolase (Cel7B) heterologously produced in a recombinant Trichoderma
      reesei were purified and studied in hydrolysis (50 degrees C, pH 6.0) of
      crystalline and amorphous cellulose. To improve their efficiency, M. albomyces
      cellulases naturally harboring no cellulose-binding module (CBM) were genetically
      modified to carry the CBM of T. reesei CBHI/Cel7A, and were studied under similar
      experimental conditions. Hydrolysis performance and product profiles were used to
      evaluate hydrolytic features of the investigated enzymes. Each cellulase proved
      to be active against the tested substrates; the cellobiohydrolase Cel7B had
      greater activity than the endoglucanases Cel45A and Cel7A against crystalline
      cellulose, whereas in the case of amorphous substrate the order was reversed.
      Evidence of synergism was observed when mixtures of the novel enzymes were
      applied in a constant total protein dosage. Presence of the CBM improved the
      hydrolytic potential of each enzyme in all experimental configurations; it had a
      greater effect on the endoglucanases Cel45A and Cel7A than the cellobiohydrolase
      Cel7B, especially against crystalline substrate. The novel cellobiohydrolase
      performed comparably to the major cellobiohydrolase of T. reesei (CBHI/Cel7A)
      under the applied experimental conditions.

PMID- 18635284
TI  - Relationship between primary tumor fluorodeoxyglucose uptake and nodal or distant
      metastases at presentation in T1 stage non-small cell lung cancer.
AB  - Many studies have shown that FDG uptake is related to prognosis of non-small cell
      lung cancer, and metastasis is the major cause of death due to lung cancer
      patients. However, the FDG uptake of primary tumor in relation to nodal or
      distant metastasis at presentation has not been studied directly. Newly diagnosed
      non-small cell lung cancer patients who accepted (18)F-FDG PET/CT staging in the
      nuclear medicine center of Shandong Cancer Hospital between 1 June 2004 and 1
      October 2007 were retrospectively reviewed. One hundred and seven patients with
      clinical T1 stage and definited histologic or cytologic evidence were enrolled
      and analyzed. Significant differences were observed in primary tumor SUVmax for
      different stages (Stage Ia-IV, P=0.004), different N status (N(0)M(0) vs. N(1
      3)M(0), P=0.008) and tumors absence any spread vs. presence distant metastasis
      (N(0)M(0) vs. M(1), P=0.000). Spearman rank analysis showed moderate correlations
      between SUVmax and different N or M status (r=0.369, P=0.000 for Stage Ia-IV;
      r=0.337, P=0.004 for N(0)M(0) vs. N(1-3)M(0); r=0.474, P=0.000 for N(0)M(0) vs.
      M(1); respectively). There was a statistically significant increase in the
      probability of metastases at presentation with each unit increase in SUVmax.
      (logistic regression model, OR=1.469; 95% CI, 1.175-1.836; P=0.001). These
      results suggest that FDG uptake is a potential indicator of metastases in small
      primary lesion of non-small cell lung cancer.

PMID- 18635285
TI  - An open phase II trial of gemcitabine, oxaliplatin and vinorelbine combination as
      first-line therapy in advanced non-small cell lung cancer patients.
AB  - The purpose of this multicentric Phase II study was to evaluate the safety and
      efficacy of a gemcitabine/oxaliplatin/vinorelbine combination as first-line
      therapy in advanced non-small cell lung cancer patients. Patients followed a
      fortnightly drug schedule, receiving on day 1, vinorelbine 25mg/m(2) (20-min
      infusion); gemcitabine 700 mg/m(2) (70-min infusion, fixed 10mg/m(2)/min); and on
      day 2, oxaliplatin 85 mg/m(2) (2-h infusion). Thirty-nine patients with a median
      age of 58 years received a total of 306 cycles (median 8 cycles); 67% were males.
      Most had adenocarcinoma (51%), large-cell (23%) and squamous cell carcinoma
      (21%); 15% had stage IIIB and 85% stage IV. There was one complete response (3%;
      95% CI: 0.1-13%), 15 partial responses (PR) (38%; 95% CI: 23-55%), and 13
      patients with stable disease (33%; 95% CI: 19-50%) of at least 2 months duration,
      for an overall non-progression rate of 74%. Median progression-free survival
      (PFS) was 4.1 months (95% CI: 3.1-8.7) and overall survival was 11.7 months (95%
      CI: 7.7-19.4). No treatment-related deaths occurred and very few grade 3-4 events
      were observed. Overall, the regimen was well tolerated and the planned
      recommended dose intensity was safely delivered to more than 95% of patients.
      This triple combination therapy study yielded favourable efficacy and toxicity
      results, which merit further evaluation in prospective randomised trials.

PMID- 18635286
TI  - Optimal design of pump-and-treat systems under uncertain hydraulic conductivity
      and plume distribution.
AB  - In this work, we present a stochastic optimal control framework for assisting the
      management of the cleanup by pump-and-treat of polluted shallow aquifers. In the
      problem being investigated, hydraulic conductivity distribution and dissolved
      contaminant plume location are considered as the uncertain variables. The
      framework considers the subdivision of the cleanup horizon in a number of stress
      periods over which the pumping policy implemented until that stage is dynamically
      adjusted based upon new information that has become available in the previous
      stages. In particular, by following a geostatistical approach, we study the idea
      of monitoring the cumulative contaminant mass extracted from the installed
      recovery wells, and using these measurements to generate conditional realizations
      of the hydraulic conductivity field. These realizations are thus used to obtain a
      more accurate evaluation of the initial plume distribution, and modify
      accordingly the design of the pump-and-treat system for the remainder of the
      remedial process. The study indicates that measurements of contaminant mass
      extracted from pumping wells retain valuable information about the plume location
      and the spatial heterogeneity characterizing the hydraulic conductivity field.
      However, such an information may prove quite soft, particularly in the instances
      where recovery wells are installed in regions where contaminant concentration is
      low or zero. On the other hand, integrated solute mass measurements may
      effectively allow for reducing parameter uncertainty and identifying the plume
      distribution if more recovery wells are available, in particular in the early
      stages of the cleanup process.

PMID- 18635287
TI  - PKA and Epac1 regulate endothelial integrity and migration through parallel and
      independent pathways.
AB  - The vascular endothelium provides a semi-permeable barrier, which restricts the
      passage of fluid, macromolecules and cells to the surrounding tissues. Cyclic AMP
      promotes endothelial barrier function and protects the endothelium against pro
      inflammatory mediators. This study analyzed the relative contribution of two cAMP
      targets, PKA and Epac1, to the control of endothelial barrier function and
      endothelial cell migration. Real-time recording of transendothelial electrical
      resistance showed that activation of either PKA or Epac1 with specific cAMP
      analogues increases endothelial barrier function and promotes endothelial cell
      migration. In addition, reduction of Epac1 expression showed that Epac1 and PKA
      control endothelial integrity and cell motility by two independent and
      complementary signaling pathways. We demonstrate that integrin-mediated adhesion
      is required for PKA, but not Epac1-Rap1-driven stimulation of endothelial barrier
      function. In contrast, both PKA- and Epac1-stimulated endothelial cell migration
      requires integrin function. These data show that activation of Epac1 and PKA by
      cAMP results in the stimulation of two parallel, independent signaling pathways
      that positively regulate endothelial integrity and cell migration, which is
      important for recovery after endothelial damage and for restoration of
      compromised endothelial barrier function.

PMID- 18635288
TI  - Effects of neighboring sequence environment in predicting cleavage sites of
      signal peptides.
AB  - Signal peptide has a pivotal role in the translocation of secretory protein. Some
      models have been designed to predict its cleavage site. It is reported that the
      cleavage site has relationship with the neighboring sequence environment, i.e.,
      hydrophobic core h-region, and the specific patterns in c-region. In some
      studies, this finding does facilitate the prediction of cleavage site. However,
      in these models, sequence environment information is merely taken account of as
      model inputs and no detailed investigation into its effect on the prediction of
      cleavage site has been made. In this work, we analyze the constraint on cleave
      site placed by the hydrophobic core of signal peptide and then use it to improve
      the performance of the signal peptide cleavage site prediction. Our model is
      designed as follows: firstly, a sliding window is used to scan sample and
      artificial neural network (ANN) is employed to give cleavage site/non-cleavage
      site scores. Then, based on an estimated hydrophobic h-region a correcting
      function is proposed to improve the prediction result, in which the sequence
      environment is taken into account. A trend of cleavage site is indicated by our
      analysis for each position, which is consistent with experimental findings.
      Through this correcting step, the improvement of prediction accuracy is over 7%.
      It therefore demonstrates the neighboring sequence environment is helpful for
      determination of cleavage site. Program written in Matlab can be downloaded from
      http://www.scucic.cn/combined model/source code.html.

PMID- 18635290
TI  - Generation-dependent encapsulation/electrostatic attachment of phenobarbital
      molecules by poly(amidoamine) dendrimers: Evidence from 2D-NOESY investigations.
AB  - The interactions of phenobarbital with different generations of amine-terminated
      poly(amidoamine) (PAMAM) dendrimers were investigated by using two dimensional
      nuclear Overhauser effect spectroscopic (2D-NOESY) investigations. The NOESY
      spectra clearly showed that there were cross-peaks from NOE interactions between
      the protons of phenobarbital and the protons in interior cavities of generation 5
      or generation 6 PAMAM dendrimers but none of such cross-peaks was found in the
      case of generation 3 or generation 4 dendrimers. The NOESY analysis, together
      with aqueous solubility data, suggested that higher generation dendrimers are
      more capable of encapsulating phenobarbital molecules into the interior cavities
      than lower generation dendrimers, and that lower generation dendrimers are much
      easier for the electrostatic attachment of phenobarbital molecules than higher
      ones at a fixed mass concentration.

PMID- 18635289
TI  - Shorter telomeres may indicate dementia status in older individuals with Down
      syndrome.
AB  - We have recently reported reduced telomere length in T lymphocytes of individuals
      with Down syndrome (DS) and dementia due to Alzheimer's disease (AD). We have now
      replicated and extended that study by finding that people with DS and mild
      cognitive impairment (MCI-DS) also have shorter telomeres than people with DS
      without MCI-DS. Additional new findings demonstrated that light intensity
      measurements from chromosome 21 alone, or in concert with chromosomes 1, 2, and
      16, exhibited shorter telomeres in adults with DS and with either dementia or MCI
      DS compared to aging per se. Chromosome 21 measurements appeared to be especially
      promising for use as a biomarker because there was no overlap in the distribution
      of light intensity measurement scores between demented or MCI-DS and non-demented
      participants. Given that early clinical symptoms of AD can be very difficult to
      recognize in this population of adults due to their pre-existing cognitive
      impairments, a valid biomarker would be of great value. Early detection is
      especially important because it would allow treatments to begin before
      significant damage to the central nervous system has occurred. Our findings
      suggest that it may be feasible to use telomere shortening as a biomarker for
      accurately inferring dementia status.

PMID- 18635291
TI  - [Necrotizing folliculitis in Behcet's disease].
AB  - We report a 24-year-old man with a known Behcet's disease who was lost to follow
      up for a year. The patient was admitted for the association of scrotal ulceration
      and inguinal folliculitis, suggesting a Behcet's disease flare-up. Necrotizing
      course of the folliculitis led to the diagnosis of skin infection caused by a
      community-acquired methicillin-resistant Staphylococcus aureus strain, carrying
      Panton-Valentine leukocidin genes. Bacteriological analysis should be mandatory
      in the absence of specific criteria for the diagnosis of Behcet's disease.

PMID- 18635292
TI  - Effect of bamboo culm extract on oxidative stress and genetic expression: bamboo
      culm extract ameliorates cell adhesion molecule expression and NFkappaB activity
      through the suppression of the oxidative stress.
AB  - BACKGROUND & AIMS: This study was designed to investigate whether bamboo culm
      extract (BCE) supplementation may ameliorate risk factors of cardiovascular
      diseases, such as hypercholesterolemia. METHODS: Oxidative stress and
      inflammatory mediators in plasma, livers of C57BL/6 mice fed high-cholesterol
      diet and calf pulmonary artery endothelial (CPAE) cells. Briefly, C57BL/6 mice
      were fed the high-cholesterol diet which was supplemented with 1% (w/w), or 3%
      (w/w) of BCE for 16 weeks. The concentration of total cholesterol, LDL
      cholesterol, HDL-cholesterol level and atherogenic index were measured. Plasma
      TEAC value, hepatic thiobarbituric acid reactive substances (TBARS), protein
      carbonyl values and hepatic antioxidant enzyme activities, such as Cu,Zn
      superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase (GSH-Px), GSH
      reductase and catalase were determined. In addition, hepatic nuclear factor kappa
      B activities were detected. In the calf pulmonary artery endothelial (CPAE) cells
      stimulated with lipopolysaccharide, the expression of vascular cell adhesion
      molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) were
      measured. RESULTS: Plasma cholesterol level was decreased, while HDL-cholesterol
      was increased, thus atherogenic index was lowered in BCE-supplemented animals.
      Plasma trolox equivalent and hepatic thiobarbituric acid reactive substances and
      protein carbonyl values were lowered significantly in BCE groups (p<0.05) in a
      dose-dependent manner. Hepatic antioxidative enzyme activities, such as Cu,Zn
      superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase (GSH-P), GSH
      reductase, and catalase were elevated in mice fed BCE-supplemented diets
      (p<0.05). Nuclear factor kappa B activities of livers and vascular cell adhesion
      molecule-1 and intracellular cell adhesion molecule-1 expressions in CPAE cells
      stimulated with lipopolysaccharide were significantly lowered in BCE groups
      (p<0.05). CONCLUSION: These results suggest that BCE supplementation may modulate
      lipoprotein composition and attenuate oxidative stress by elevated antioxidative
      processes, thus suppressing inflammatory mediator activation as possible
      mechanism of its anti-atherogenic effect.

PMID- 18635293
TI  - Assessment of long chain n-3 polyunsaturated fatty acid status and clinical
      outcome in adults receiving home parenteral nutrition.
AB  - BACKGROUND & AIMS: Long term parenteral nutrition rarely supplies the long chain
      n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA),
      docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). The aim of this study
      was to assess long chain n-3 PUFA status in patients receiving home parenteral
      nutrition (HPN). METHODS: Plasma phospholipid fatty acids were measured in 64
      adult HPN patients and compared with 54 age, sex and BMI matched controls.
      Logistic regression analysis was used to identify factors related to plasma fatty
      acid fractions in the HPN patients, and to identify factors associated with the
      risk of clinical complications. RESULTS: Plasma phospholipid fractions of EPA,
      DPA and DHA were significantly lower in patients receiving HPN. Factors
      independently associated with low fractions included high parenteral energy
      provision, low parenteral lipid intake, low BMI and prolonged duration of HPN.
      Long chain n-3 PUFA fractions were not associated with incidence of either
      central venous catheter associated infection or central venous thrombosis.
      However, the fraction of EPA were inversely associated with plasma alkaline
      phosphatase concentrations. CONCLUSIONS: This study demonstrates abnormal long
      chain n-3 PUFA profiles in patients receiving HPN. Reduced fatty acid intake may
      be partly responsible. Fatty acid metabolism may also be altered.

PMID- 18635294
TI  - Biomechanical studies on cervical total disc arthroplasty: a literature review.
AB  - BACKGROUND: Many models of cervical disc prostheses are currently commercially
      available or under clinical trial, and are based on several design concepts and
      built employing different materials. This paper is targeted to the understanding
      of the possible relationships between the geometrical, mechanical and material
      properties of the various cervical disc prostheses and the restoration of a
      correct biomechanics of the implanted spine. METHODS: Papers about cervical disc
      arthroplasty, based on ex vivo testing, mathematical models, and radiographic
      measurements, were included in the present review. FINDINGS: Although disc
      arthroplasty was found to be generally able to preserve a nearly physiological
      motion in the cervical spine, several alterations in the spine biomechanics due
      to disc arthroplasty were reported in the literature. An increase of the range of
      motion at the implanted level was observed in some ex vivo studies. Loss of
      mobility and heterotopic ossification were reported in radiographic
      investigations. Loss of lordosis at the implanted level was detected as well.
      Wear debris was usually found very limited and device stability seemed not to be
      an actual problem. INTERPRETATION: The possible relationships between the
      observed alterations in the spine biomechanics after disc arthroplasty and the
      properties of the various cervical disc prostheses have been reviewed. Clinical
      studies are needed to assess the validity of the considerations inferred from the
      biomechanical papers.

PMID- 18635295
TI  - Wrist and carpal tunnel size and shape measurements: effects of posture.
AB  - BACKGROUND: Wrist anthropometrics and posture have been implicated in the
      development of carpal tunnel syndrome, yet it remains unclear how external
      measurements relate to carpal tunnel parameters in neutral and non-neutral
      postures. The purposes of this study were (i) to evaluate the effect of slice
      orientation on several indices of carpal tunnel size and shape and (ii) to
      examine the relationship between carpal tunnel and external wrist dimensions.
      METHODS: Three-dimensional static models were generated to measure carpal tunnel
      and wrist parameters for six wrists in three wrist postures (30 degrees flexion,
      neutral and 30 degrees extension). A simulated imaging plane enabled measurement
      of four carpal tunnel dimensions and two shape indices throughout the tunnel
      length, using "axial" and "tunnel" slice orientations (perpendicular to forearm
      and tunnel, respectively). FINDINGS: Correction for tunnel orientation eliminated
      posture-related changes in tunnel size and shape noted at the distal end using
      "axial" alignment. "Tunnel" alignment reduced average carpal tunnel area and
      depth by nearly 15% in extension, but generally less than 5% in neutral and 2% in
      flexion. Subsequently, "tunnel" alignment also decreased carpal tunnel and non
      circularity ratios to reveal a flatter, more elliptical shape throughout the
      tunnel in extension than neutral and flexion. Wrist dimensions correlated
      significantly with tunnel dimensions, but not tunnel shape, while wrist shape
      correlated significantly with tunnel shape, area and depth. INTERPRETATIONS:
      Slice alignment with the carpal tunnel may improve the consistency of findings
      within and between patient and control populations, and enhance the diagnostic
      utility of imaging in clinical settings.

PMID- 18635296
TI  - Influence of synthetic surfactants on the uptake of Pd, Cd and Pb by the marine
      macroalga, Ulva lactuca.
AB  - Uptake of Pd, Cd and Pb by the marine macroalga, Ulva lactuca, has been studied
      in the presence of an anionic (sodium dodecyl sulphate, SDS), cationic
      (hexadecyltrimethylammonium bromide; HDTMA) and non-ionic (Triton X-100; TX)
      surfactant. Compared with the surfactant-free system, metal sorption was reduced
      in the presence of SDS or TX. Neither surfactant, however, had any measurable
      impact on cell membrane permeability, determined by leakage of dissolved free
      amino acids (DFAA), or on metal internalisation. We attribute these observations
      to the stabilisation of aqueous Cd and Pb by SDS and the shielding of otherwise
      amenable sorption sites by TX. Presence of HDTMA resulted in a reduction in the
      extent of both sorption and internalisation of all metals and a significant
      increase in the leakage of DFAA. Thus, by enhancing membrane permeability, HDTMA
      exerts the greatest influence on metal behaviour in the presence of U. lactuca.

PMID- 18635297
TI  - Comparison of naphthalene bioavailability determined by whole-cell biosensing and
      availability determined by extraction with Tenax.
AB  - A rapid biological method for the determination of the bioavailability of
      naphthalene was developed and its value as an alternative to extraction-based
      chemical approaches demonstrated. Genetically engineered whole-cell biosensors
      are used to determine bioavailable naphthalene and their responses compared with
      results from Tenax extraction and chemical analysis. Results show a 1:1
      correlation between biosensor results and chemical analyses for naphthalene
      contaminated model materials and sediments, but the biosensor assay is much
      faster. This work demonstrates that biosensor technology can perform as well as
      standard chemical methods, though with some advantages including the inherent
      biological relevance of the response, rapid response time, and potential for
      field deployment. A survey of results from this work and the literature shows
      that bioavailability under non-equilibrium conditions nonetheless correlates well
      with K(oc) or K(d). A rationale is provided wherein chemical resistance is
      speculated to be operative.

PMID- 18635298
TI  - Release of hexachlorocyclohexanes from historically and freshly contaminated
      soils in China: implications for fate and regulation.
AB  - Hexachlorocyclohexanes (HCHs) were produced and used in large quantity worldwide
      and are common soil pollutants. In this study, desorption of alpha-HCH and gamma
      HCH from two soil samples collected from a historical pesticide plant in Tianjin,
      China, was examined. As a comparison, desorption of freshly sorbed gamma-HCH was
      examined, using five typical Chinese soils. Strong resistant desorption was
      observed for both historically contaminated and freshly contaminated soils, and
      desorption results were well modeled with a biphasic desorption isotherm. The
      unique thermodynamic characteristics associated with the desorption-resistant
      fraction indicated that physical constraint within soil organic matrices was
      likely the predominant mechanism controlling resistant desorption. Resistant
      desorption could have significant effects on fate and exposure of HCHs in soil
      environment. More accurate biphasic desorption models that take into account of
      the resistant desorption can be used to facilitate regulating, management and
      remediation of HCH-contaminated sites.

PMID- 18635299
TI  - Mass balance and long-term fate of PCDD/Fs in a lagoon sediment and paddy soil,
      Niigata, Japan.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) in a sediment core and in samples of surface sediment and paddy soil
      collected from the Toyano lagoon and Kameda basin in Niigata, Japan, were
      analyzed to elucidate the temporal trends of their concentrations in the lagoon
      sediment and the relationship between the sediment and the paddy soil. The mass
      balance of these pollutants was also estimated to determine their long-term fate
      in surface waters. An analysis by chemical mass balance identified the
      agrochemicals pentachlorophenol and 2,4,6-trichlorophenyl 4-nitrophenyl ether as
      the major sources of PCDD/Fs. On the basis of the findings regarding the mass
      balance in the Kameda basin over the last 40 years, we estimate that more than
      half the input of PCDD/Fs to the Kameda basin has disappeared. We suggest that
      the PCDD/Fs that flowed out from the paddy fields have been transferred to the
      lower basin.

PMID- 18635300
TI  - Implementation of the dermal sensitization Quantitative Risk Assessment (QRA) for
      fragrance ingredients.
AB  - Significant developments have recently been incorporated in the way dermal
      sensitization risk assessments are conducted for fragrance ingredients. Based on
      the RIFM Expert Panel's recommendation, RIFM and IFRA have formally adopted the
      QRA approach, refined for fragrance ingredients identified as contact allergens,
      as the core strategy for primary prevention of dermal sensitization to these
      materials in consumer products. This new methodology is a major improvement over
      the former approach because it specifically addresses the elements of exposure
      based risk assessment that are unique to the induction of dermal sensitization,
      while being consistent with the principles of toxicological risk assessment. This
      methodology will be used to determine global fragrance industry product
      management practices (IFRA Standards) for potentially sensitizing fragrance
      ingredients, the first of which was implemented in May 2006 with the 40th
      Amendment to the IFRA Code of Practice. It contained the first four IFRA
      Standards based on the QRA, limiting the use of the materials for 11 individual
      product categories. One of the first four IFRA Standards based on the QRA was on
      the fragrance material citral. The basis for the acceptable exposure limits are
      presented in this paper.

PMID- 18635301
TI  - Relationship of socioeconomic status to C-reactive protein and arterial stiffness
      in urban Japanese civil servants.
AB  - This study investigates whether the two socioeconomic status indicators,
      educational level and employment grade, are associated with C-reactive protein
      (CRP) levels and arterial stiffness among Japanese urban civil servants. Brachial
      ankle pulse-wave velocity (baPWV) as an indicator of arterial stiffness, CRP,
      occupational stress and conventional risk factors were evaluated in 3412 men and
      854 women. Although the socioeconomic gradient showed a significant association
      with the CRP levels in men after adjustment for age, the significance disappeared
      after multivariate adjustment, whereas in women, the socioeconomic gradient
      showed no significant association with the CRP levels. In men, educational level
      was significantly associated with the baPWV value after adjustment for
      conventional risk factors, CRP and occupational stress (P for trend <0.0001).
      With regards to employment grade, only low-level non-manual workers had a
      significantly lower baPWV value as compared to manual workers at a fully adjusted
      model, and trend significance disappeared. However, in women, neither educational
      level nor employment grade was associated with the baPWV value. In summary, the
      socioeconomic gradient, especially the educational level, was significantly
      inversely related to the baPWV value in men. In women, the socioeconomic gradient
      was not related to the baPWV value. An inverse relationship between the
      socioeconomic gradient and CRP levels was found in men only after age adjustment.
      We suggest that because the educational level is an important aspect in the
      adolescent environment and hence might influence the future lifestyle, early
      health education should be provided to prevent an unfavourable lifestyle and
      atherosclerotic diseases in later life.

PMID- 18635302
TI  - How important are individual, household and commune characteristics in explaining
      utilization of maternal health services in Vietnam?
AB  - Using Vietnam's latest National Household Survey data for 2001-2002 this paper
      assesses the influence of individual, household and commune-level characteristics
      on a woman's decision to seek prenatal care, on the number of prenatal visits,
      and on the choice between giving birth at a health facility or at home. The
      decision to use any care and the number of prenatal visits is modeled using a two
      part model. A random intercept logistic model is used to capture the influence of
      unobserved commune-specific factors found in the data regarding a woman's
      decision to give birth at a health facility rather than at home. The results show
      that access to prenatal care and delivery assistance is limited by observed
      barriers such as low income, low education, ethnicity, geographical isolation and
      a high poverty rate in the community. More specifically, more prenatal visits
      increase the likelihood of giving birth at a health facility. Having compulsory
      health insurance increases the odds of giving birth at a health facility for
      middle and high income women. In contrast, health insurance for the poor
      increases the likelihood of having more prenatal visits but has little effect on
      the place of delivery. These results suggest that the existing safe motherhood
      programs should be linked with the objectives of social development programs such
      as poverty reduction, and that policy makers need to view both the individual and
      the commune as appropriate units for policy targeting.

PMID- 18635303
TI  - Reduced misinformation effects following saccadic bilateral eye movements.
AB  - The effects of saccadic bilateral (horizontal) eye movements on memory for a
      visual event narrative were investigated. In the study phase, participants were
      exposed to a set of pictures accompanied by a verbal commentary describing the
      events depicted in the pictures. Next, the participants were asked either
      misleading or control questions about the depicted event and were then asked to
      engage in 30s of bilateral vs. vertical vs. no eye movements. Finally,
      recognition memory was tested using the remember-know procedure. It was found
      that bilateral eye movements increased true memory for the event, increased
      recollection, and decreased the magnitude of the misinformation effect. The
      findings are discussed in terms of source monitoring, dual-process theories of
      memory and the potential neural foundations of such effects.

PMID- 18635304
TI  - Placebo-controlled trial evaluating safety with 12-months continuous use of 6%
      hydrogen peroxide whitening strips.
AB  - OBJECTIVE: To assess the safety and tolerability of 6% hydrogen peroxide
      whitening strips over 12 months. METHODS: 80 adults were randomly assigned
      equally to one of two treatments: 6% hydrogen peroxide strips or placebo strips.
      Strips were worn 5 min daily for 12 months. Safety and tolerability were assessed
      via oral status interviews and oral examinations at baseline and after 1, 2, 3,
      6, 9, and 12 months of use. RESULTS: Tooth sensitivity and oral irritation were
      the two most common adverse events. After 12 months use, tooth sensitivity was
      reported by 10% of subjects in the 6% strip group with a 95% confidence interval
      (CI) of (2.8%, 23.7%) and 5% of subjects in the placebo group with a 95% CI of
      (0.6%, 16.9%). The occurrence of reported oral irritation was 0% in the 6% strip
      group with a 95% CI of (0%, 8.8%) and 2.5% in the placebo strip group with a 95%
      CI of (0.1%, 13.2%). The occurrence of observed oral irritation was also similar
      between groups. The groups did not differ significantly (p>0.67) for the percent
      of subjects with each type of adverse event. In the 6% strip group, two subjects
      discontinued product use due to an adverse event (tooth sensitivity) compared to
      no subjects in the placebo group. Groups did not differ significantly (p>0.49)
      with respect to this outcome. CONCLUSION: Use of 6% hydrogen peroxide whitening
      strips over 12 months resulted in a safety profile similar to that seen with
      placebo strips.

PMID- 18635305
TI  - The whitening effect of enzymatic bleaching on tetracycline.
AB  - OBJECTIVE: Carbamide peroxide and hydrogen peroxide have been used as tooth
      whitening agents. The aim of this paper was to determine the efficiency of
      several enzyme-containing whitening systems. A method to determine the rate of
      'in vitro' tetracycline whitening was also developed. METHODS: We determined the
      tetracycline whitening ability of carbamide peroxide and hydrogen peroxide, and
      the influence of peroxidase and lactoperoxidase on this tetracycline whitening
      rate. RESULTS: High peroxidase and lactoperoxidase concentrations increased the
      rate of tetracycline decoloration obtained with carbamide peroxide or hydrogen
      peroxide. The decoloration rate observed was lower when the glucose/glucose
      oxidase system was used to generate hydrogen peroxide 'in situ'. The presence of
      peroxidase increased the decoloration rate of extracted teeth obtained with
      carbamide. CONCLUSIONS: Enzymes such as peroxidase could be used as whitening
      catalysts to increase the rate of tetracycline decoloration.

PMID- 18635307
TI  - Attitudes toward automated external defibrillator use in Japan.
AB  - BACKGROUND: The American Heart Association 2005 Guidelines recommend immediate
      defibrillation for ventricular fibrillation (VF) of short duration, such as
      witnessed sudden cardiac arrest. However, it is unclear if public-access
      automated external defibrillators (AEDs) would actually be used in Japan, because
      there have been few studies about public attitudes regarding AED use. Therefore,
      we examined Japanese attitudes toward AED use. METHODS AND RESULTS: Between
      February and March 2006, 3328 individuals, including high school students,
      teachers, emergency medical technicians (EMTs), medical nurses, and medical
      students, were asked about AED knowledge and their willingness to operate an AED.
      All EMTs, 86% of nurses, and 90% of medical students knew how to use AEDs, while
      only 15% of high school students and 44% of teachers had such knowledge. All
      EMTs, 78% of nurses, and 94% of medical students reported they would 'definitely'
      use the AED, but only 12% of high school students and 35% of teachers gave this
      reply. The reasons for unwillingness to operate AEDs among both laypeople and
      health care providers were poor of awareness of what AED is and/or how to use an
      AED. However, 83% of students and 81% of teachers with AED knowledge reported
      they would 'definitely' use the AED. CONCLUSIONS: Many non-medical people in
      Japan would be unwilling to operate an AED, because they do not know what AED is
      and/or how to use an AED. However, many would be willing to operate AEDs if they
      had better understanding of AEDs. Thus, it is necessary to improve public
      knowledge of AEDs and AED use.

PMID- 18635306
TI  - Instructions to "push as hard as you can" improve average chest compression depth
      in dispatcher-assisted cardiopulmonary resuscitation.
AB  - BACKGROUND AND OBJECTIVE: Cardiopulmonary resuscitation (CPR) with adequate chest
      compression depth appears to improve first shock success in cardiac arrest. We
      evaluate the effect of simplification of chest compression instructions on
      compression depth in dispatcher-assisted CPR protocol. METHODS: Data from two
      randomized, double-blinded, controlled trials with identical methodology were
      combined to obtain 332 records for this analysis. Subjects were randomized to
      either modified Medical Priority Dispatch System (MPDS) v11.2 protocol or a new
      simplified protocol. The main difference between the protocols was the
      instruction to "push as hard as you can" in the simplified protocol, compared to
      "push down firmly 2in. (5cm)" in MPDS. Data were recorded via a Laerdal
      ResusciAnne SkillReporter manikin. Primary outcome measures included: chest
      compression depth, proportion of compressions without error, with adequate depth
      and with total release. RESULTS: Instructions to "push as hard as you can",
      compared to "push down firmly 2in. (5cm)", resulted in improved chest compression
      depth (36.4 mm vs. 29.7 mm, p<0.0001), and improved median proportion of chest
      compressions done to the correct depth (32% vs. <1%, p<0.0001). No significant
      difference in median proportion of compressions with total release (100% for
      both) and average compression rate (99.7 min(-1) vs. 97.5 min(-1), p<0.56) was
      found. CONCLUSIONS: Modifying dispatcher-assisted CPR instructions by changing
      "push down firmly 2in. (5cm)" to "push as hard as you can" achieved improvement
      in chest compression depth at no cost to total release or average chest
      compression rate.

PMID- 18635308
TI  - Lipoteichoic acid induces delayed myocardial protection in isolated rat hearts: a
      comparison with endotoxin.
AB  - OBJECTIVE: Preconditioning with bacterial wall fragments lipopolysaccharide (LPS)
      or lipoteichoic acid (LTA) reduce myocardial infarct size after ischaemia and
      reperfusion (I/R) in rats. Preconditioning with LTA reduces neutrophil
      accumulation during reperfusion and thereby ameliorates one of myocardial
      reperfusion injury's most important mechanisms. In this study, we use an ex vivo
      model of regional myocardial I/R to investigate LTA versus LPS induced
      preconditioning in a system devoid of leukocytes. METHODS: Rats were subjected to
      LTA or LPS with or without dexamethasone pre-treatment. Twenty-four hours after
      LTA or LPS challenge, hearts were removed and retrogradely perfused in a
      Langendorff set-up. Hearts underwent 20 min of regional ischaemia followed by 2 h
      of reperfusion. Ischaemic preconditioning (IPC) was performed as a positive
      control. Myocardial infarct size was determined as the primary end-point.
      RESULTS: LTA and LPS preconditioning both lead to a marked reduction in infarct
      size similar to IPC, however, no significant differences were found between LTA
      and LPS. The reduction in infarct size was abrogated by dexamethasone pre
      treatment. CONCLUSION: We conclude that preconditioning with LTA and likewise
      with LPS confers myocardial protection in an ex vivo setting devoid of
      leukocytes. Dexamethasone inhibits preconditioning, suggesting that the
      underlying mechanism is dependent upon induction of a systemic inflammatory
      response to a LTA or LPS stimulus.

PMID- 18635309
TI  - Closing the knowledge-performance gap: an audit of medical management for severe
      paediatric trauma in Flanders (Belgium).
AB  - AIMS: Considerable variability in (paediatric) trauma care has been reported. We
      wanted to audit current practice in Flanders (Belgium). METHODS: The PENTA
      network prospectively collected data on paediatric trauma patients in a
      representative sample of Flemish hospitals during 2005. All cases with an
      ISS>or=13 and sufficient data availability were withheld for panel evaluation
      (n=92). Two trained experts reviewed the medical care provided in the first hours
      after trauma, based on available evidence and existing universal guidelines.
      'Defaults' were only withheld as such if there was 100% consensus. At random,
      about 25% of cases were also reviewed by two other experts in order to assess
      interobserver variability. RESULTS: In the 92 cases, 264 defaults were
      recognised. 25.4% of all defaults were thought to have a direct impact on the
      individual patient's outcome. Specific difficulties were observed with, e.g.
      cervical spine management (18/82 relevant cases), pCO2 and global respiratory
      management (38/92), fluid management (29/92) and analgesia (27/89). The agreement
      between the two panels was good for defaults identified (crude agreement 74.8%),
      yet only fair for the presumed impact on outcome (crude agreement 58.3%).
      CONCLUSIONS: We audited paediatric trauma care in Flanders and identified several
      problem areas (often in basic areas of paediatric life support). The inherent
      degree of interobserver variability does not diminish the importance of these
      findings. More performance-based teaching and timely recertification may have a
      positive impact on the quality of the care delivered.

PMID- 18635310
TI  - Cerebral ischaemia following cardiopulmonary resuscitation in pigs.

PMID- 18635311
TI  - PU.1 expression is restored upon treatment of chronic myeloid leukemia patients.
AB  - The PU.1 transcription factor is a crucial regulator of hematopoiesis which
      expression is altered in various leukemic processes. Our previous work in chronic
      myeloid leukemia (CML) cells demonstrated that interferon-alpha upregulated PU.1
      expression. Here we show that expression of PU.1 is severely impaired in patients
      with CML at diagnosis. However, the PU.1 suppression is abrogated in patients in
      remission, after interferon-alpha or imatinib treatment. These effects are not
      found in patients with other myeloproliferative diseases such as polycythemia
      vera or essential thrombocythemia. PU.1 could, therefore, be used as an
      additional marker of the response to the treatment of the CML.

PMID- 18635312
TI  - Histone deacetylase inhibitors and genomic instability.
AB  - Histone deacetylase inhibitors (HDACIs) are a promising new class of anticancer
      drugs. However, their mechanism of action has not been fully elucidated. Most
      studies have investigated the effect of HDACIs on the regulation of gene
      transcription. HDAC inhibition also leads to genomic instability by a variety of
      mechanisms. This phenomenon, which has been largely overlooked, may contribute to
      the cytotoxic effects of these drugs. Indeed, HDACIs sensitize DNA to exogenous
      genotoxic damage and induce the generation of reactive oxygen species. Moreover,
      HDACIs target mitosis resulting in chromosome segregation defects. Here, we
      review the effects of HDACI treatment on DNA damage and repair, and chromosome
      segregation control.

PMID- 18635313
TI  - A seasonality study of polychlorinated dibenzo-p-dioxins and dibenzofurans in
      ambient air in Kaohsiung (Taiwan) clustered with metallurgical industries.
AB  - As a comprehensive monitoring survey on polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) in Kaohsiung, 40 ambient air samples taken from 10
      locations in four seasons were studied. PCDD/F concentrations at 0.312-4.58pgNm(
      3) and I-TEQ values, ranging from 0.0319 to 0.256pgNm(-3) were determined for
      these samples, which were comparable to those of other urban cities. However,
      unlike studies on some other urban cities, the ambient air in Kaohsiung did not
      exhibit regular seasonality in PCDD/F concentrations. All samples were
      predominated, in common, by congeners OCDD, 1,2,3,4,6,7,8-HpCDF, 1,2,3,4,6,7,8
      HpCDD, OCDF and 2,3,4,7,8-PeCDF. The congener profiles of the samples generally
      did not display any seasonal trend, either. The insignificant seasonality and
      constancy of congener profiles with time were attributed to the constant
      influence by emission sources in a metal-producing center, thereby resulting in
      high atmospheric dioxin levels in the nearby district. Principal component
      analyses identified that dioxin emissions in ambient air of the city originated
      from electric arc furnaces (EAFs) and sinter plants in the center. Concentration
      isopleth analyses assessing pollution sources and ambient air of the district
      also confirmed that its atmosphere was affected largely by the EAFs and sinter
      plants.

PMID- 18635314
TI  - Identification of produced powerful radicals involved in the mineralization of
      bisphenol A using a novel UV-Na(2)S(2)O(8)/H(2)O(2)-Fe(II,III) two-stage
      oxidation process.
AB  - A two-stage oxidation (UV-Na(2)S(2)O(8)/H(2)O(2)-Fe(II,III)) process was applied
      to mineralize bisphenol A (BPA) at pH(i) (initial pH) 7. We take advantage of the
      high oxidation potential of sulfate radicals and use persulfate as the 1st-stage
      oxidant to oxidize BPA to less complex compounds (stoichiometric ratio:
      [S(2)O(8)(2-)](0)/[BPA](0)=1). Afterwards, the traditional photo-Fenton process
      was used to mineralize those compounds to CO(2). To the best of our knowledge,
      this is the first attempt to utilize the two processes in conjunction for the
      complete degradation of BPA. During the 2nd-stage reaction, other oxidants
      (H(2)O(2) and Iron alone) were also employed to observe the extent of enhancement
      of photo-Fenton. Further, qualitative identification of both hydroxyl and sulfate
      radicals was performed to evaluate their dominance under different conditions.
      The BPA degradation in this UV/persulfate process formulated a pseudo-first-order
      kinetic model well, with a rate constant of approximately 0.038 min(-1) (25
      degrees C), 0.057 min(-1) (35 degrees C), and 0.087 min(-1) (50 degrees C),
      respectively. The much lower activation energy (DeltaE = 26 kJ mol(-1)) was
      further calculated to clarify that the thermal-effect of an illuminated system
      differs from single heat-assisted systems described in other research. Final
      total organic carbon (TOC) removal levels of BPA by the use of such two-stage
      oxidation processes were 25-34%, 25%, and 87-91% for additional Fe(II,III)
      activation, H(2)O(2) promotion, and Fe(II,III)/H(2)O(2) promotions, respectively.

PMID- 18635315
TI  - Treatment of phenolic wastewater in an anaerobic fixed bed reactor (AFBR) -
      recovery after shock loading.
AB  - An anaerobic fixed bed reactor (AFBR) was run for 550 days with a mixed microbial
      flora to stabilize synthetic wastewater that contained glucose and phenol as main
      carbon sources. The influent phenol concentration was gradually increased from 2
      to 40 mmol/l within 221 days. The microbial flora was able to adapt to this high
      phenol concentration with an average of 94% phenol removal. Microbial adaptation
      at such a high phenol concentration is not reported elsewhere. The maximum phenol
      removal observed before the phenol shock load was 39.47 mmol/l or 3.7 g phenol/l
      at a hydraulic retention time (HRT) of 2.5 days and an organic loading rate (OLR)
      of 5.3 g/l.d which amounts to a phenol removal rate of ca. 15.8 mmol phenol/l.d.
      The chemical oxygen demand (COD) removal before exposing the reactor to a shock
      load corresponded with phenol removal. A shock load was induced in the reactor by
      increasing the phenol concentration from 40 to 50 mmol/l in the influent. The
      maximum phenol removal rate observed after shock load was 18 mmol/l.d at 5.7 g
      COD/l.d. But this was not a stable rate and a consistent drop in COD and phenol
      removal was observed for 1 week, followed by a sharp decline and production of
      fatty acids. Recovery of the reactor was possible only when no feed was provided
      to the reactor for 1 month and the phenol concentration was increased gradually.
      When glucose was omitted from the influent, unknown intermediates of anaerobic
      phenol metabolism were observed for some time.

PMID- 18635316
TI  - Removal of synthetic reactive dyes from textile wastewater by Sorel's cement.
AB  - Removal of some reactive dyes (RY-145, RR-194 and RB-B) from textile wastewater
      effluents using Sorel's cement is described. Parameters affecting dye uptake
      including contact time, reagent dosage and pH are examined and optimized. Dye
      adsorption equilibrium data are fitted well to the Langmiur isotherm rather than
      Freundlish isotherm. The adsorption isotherm indicates that the adsorption
      capacities are 107.67, 120.89 and 103.14 mg dye per gram of Sorel's cement for RY
      145, RR-194 and RB-B reactive dyes, respectively. The adsorption isotherms,
      including Langmuir constant (Q degrees and b) and Frendlich constant (K(F) and
      n), for the dyes decrease with the increase of temperature. The values of
      enthalpy change (DeltaH) for RY-145, RR-194 and RB-B dyes are -146.96, -49.23 and
      -264.86 kJ mol(-1), respectively, indicating that the removal process is
      exothermic. The sorption of the dyes is enhanced by increasing the pH, reaching a
      maximum at pH 6-11. Experimental runs conducted to measure the chemical oxygen
      demand (COD) of textile wastewater loaded with reactive dyes, reveal
      approximately 96% removal of the COD contents within 30 min under optimized
      conditions.

PMID- 18635317
TI  - Effects of strain gradients on strain measurements using geometrical phase
      analysis in the transmission electron microscope.
AB  - An analysis of the effects of lens aberrations on the phase contrast images used
      for strain measurement by geometric phase analysis (GPA) in the TEM shows that
      errors may result when strain gradients are present and when [formula: see text]
      at the reciprocal lattice spacing used for the analysis. This conclusion is
      demonstrated experimentally using a model specimen consisting of a strained Si
      layer grown epitaxially on a Si-Ge alloy substrate. Image simulations for this
      model specimen show that strain gradients can introduce oscillations in strain
      maps when the defocus is not optimized for GPA. This work also makes it possible
      to identify other potential sources of error in GPA.

PMID- 18635319
TI  - Chorangiosis: the potential role of smoking and air pollution.
AB  - Chorangiosis is considered to be strongly associated with various fetal,
      maternal, and placental disorders, including pre-eclampsia, diabetes,
      hypertension, and major congenital anomalies, and has been found to correlate
      with increased fetal morbidity and mortality. In this study, we investigated the
      pathologic effects of maternal smoking and air pollution on the pathogenesis of
      chorangiosis. We investigated 92 placentas macroscopically and microscopically
      over a 3-month period (March 2006-May 2006) at Denizli State Hospital to identify
      the frequency of chorangiosis and the potential role of maternal smoking and air
      pollution. Placental changes were examined by light microscopy after hematoxylin
      and eosin (H&E) staining and immunohistochemical evaluation of CD 34 and CD 68;
      muscle-specific actin was used to confirm the diagnosis. Among the 92 mothers
      included in the study, 33 were smokers (group I), 31 were thought to have been
      exposed to air pollution (group II), and 28 were living in rural areas free of
      air pollution and maternal smoking (group III). Chorangiosis was found in 14%
      (13/92) of all placentas: 7 (53.8%) cases were assigned to group I, 5 (38.5%) to
      group II, and 1 (7.7%) to group III. Vascular changes were found mainly in the
      smoking and air pollution groups. There appeared to be no correlation of these
      vascular changes with placental weight, parity, gestational age, major congenital
      anomalies, and maternal factors, including diabetes and pre-eclampsia. We presume
      that smoking and air pollution may contribute to the development of chorangiosis.
      We suggest that chorangiosis may be an adaptive response to maternal hypoxia, and
      studies addressing the role of smoking and air pollution in chorangiosis may
      provide new insights into the pathogenesis of this condition.

PMID- 18635318
TI  - How important are parents during the college years? A longitudinal perspective of
      indirect influences parents yield on their college teens' alcohol use.
AB  - Building on previous findings supporting the continuing influence of parents on
      their teens after they have gone to college [Turrisi, R., Jaccard, J., Taki, R.,
      Dunnam, H., & Grimes, J. (2001). Examination of the short-term efficacy of a
      parent intervention to reduce college student drinking tendencies. Psychology of
      Addictive Behaviors, 15(4), 366-372.; Turrisi, R., Padilla, K., & Wiersma, K.
      (2000). College student drinking: An examination of theoretical models of
      drinking tendencies in freshman and upperclassmen. Journal of Studies on Alcohol,
      61, 598-602.[28]], this study examined the possible indirect influence that
      parents may have on their teen's alcohol use through the selection of alcohol
      using peers in college. Friend use served as a mediator of the relationship
      between parenting characteristics and alcohol use in a longitudinal college
      sample. As part of a larger study, 392 incoming college freshmen were assessed
      for their perceptions of their parent's parenting practices, and peer alcohol
      use. Results from SEM indicated that friend alcohol use (first semester freshman
      year) mediated the relationship between parental knowledge about what their teen
      was doing in his/her free time (baseline pre-matriculation to college) and
      individual use in college (second semester freshman year). Findings suggest that
      even at this late stage of early adulthood parents continue to exhibit influence
      on the choices their teens make as far as friends, which in turn influences their
      teens' drinking in college. Implications for prevention are discussed.

PMID- 18635320
TI  - Factors associated with long-term dysphagia after definitive radiotherapy for
      locally advanced head-and-neck cancer.
AB  - PURPOSE: The use of altered fractionation radiotherapy (RT) regimens, as well as
      concomitant chemotherapy and RT, to intensify therapy for locally advanced head
      and-neck cancer can lead to increased rates of long-term dysphagia. METHODS AND
      MATERIALS: We identified 122 patients who had undergone definitive RT for locally
      advanced head-and-neck cancer, after excluding those who had been treated for a
      second or recurrent head-and-neck primary, had Stage I-II disease, developed
      locoregional recurrence, had <12 months of follow-up, or had undergone
      postoperative RT. The patient, tumor, and treatment factors were correlated with
      a composite of 3 objective endpoints as a surrogate for severe long-term
      dysphagia: percutaneous endoscopic gastrostomy tube dependence at the last follow
      up visit; aspiration on a modified barium swallow study or a clinical diagnosis
      of aspiration pneumonia; or the presence of a pharyngoesophageal stricture.
      RESULTS: A composite dysphagia outcome occurred in 38.5% of patients. On
      univariate analysis, the primary site (p = 0.01), use of concurrent chemotherapy
      (p = 0.01), RT schedule (p = 0.02), and increasing age (p = 0.04) were
      significantly associated with development of composite long-term dysphagia. The
      use of concurrent chemotherapy (p = 0.01), primary site (p = 0.02), and
      increasing age (p = 0.02) remained significant on multivariate analysis.
      CONCLUSION: The addition of concurrent chemotherapy to RT for locally advanced
      head-and-neck cancer resulted in increased long-term dysphagia. Early
      intervention using swallowing exercises, avoidance of nothing-by-mouth periods,
      and the use of intensity-modulated RT to reduce the dose to the uninvolved
      swallowing structures should be explored further in populations at greater risk
      of long-term dysphagia.

PMID- 18635321
TI  - Immunization with recombinant alpha toxin partially protects broiler chicks
      against experimental challenge with Clostridium perfringens.
AB  - Necrotic enteritis (NE) in poultry has re-emerged as a concern for poultry
      producers, due in part to banning, by many countries, of the use of antimicrobial
      growth promoters in feeds. This re-emergence has led to a search for alternative
      methods for control of the disease, particularly vaccination. The objective of
      this work was to determine if vaccination of broiler chicks with recombinant
      alpha toxin protected against experimental challenge. Broiler chicks were
      vaccinated subcutaneously at 5 and 15 days of age, followed 10 days later by
      challenge with Clostridium perfringens. Birds were challenged twice daily on 4
      consecutive days by mixing C. perfringens cultures with feed (three parts
      culture: four parts feed). Non-vaccinated birds challenged with C. perfringens
      developed NE at the rate of 87.8%, while only 54.9% of vaccinated birds developed
      lesions. In addition, non-vaccinated birds had lesion scores averaging 2.37,
      while average scores in vaccinated birds were 1.35. Vaccination produced an
      antibody response, with post-vaccination anti-alpha toxin IgG (IgY) titers in
      vaccinated birds more than 5-fold greater than in non-vaccinated birds. After
      challenge, vaccinated birds had average IgG (IgY) titers>15-fold higher than
      those in non-vaccinated birds. These results suggest that alpha toxin may serve
      as an effective immunogen, and, as such, may play a role in pathogenesis.

PMID- 18635322
TI  - An update on canine coronaviruses: viral evolution and pathobiology.
AB  - The emergence of human severe acute respiratory syndrome incited renewed interest
      in animal coronaviruses (CoVs) as potential agents of direct and indirect
      zoonoses. The reinforced epidemiological surveillance on CoVs has led to the
      identification of new viruses, genotypes, pathotypes and host variants in animals
      and humans. In dogs, a CoV associated with mild enteritis, canine coronavirus
      (CCoV), has been known since 1970s. CoV strains with different biological and
      genetic properties with respect to classical CCoV strains have been identified in
      dogs in the last few years, leading to a full reconsideration of the CoV-induced
      canine diseases. The genetic evolution of dog CoVs is paradigmatic of how CoVs
      evolve through accumulation of point mutations, insertions or deletions in the
      viral genome, that led to the emergence of new genotypes (CCoV type I), biotypes
      (pantropic CCoV) and host variants (canine respiratory coronavirus). This paper
      is a review of the current literature on the recent genetic evolution of CCoV and
      emergence of new CoVs in the dog. The significances of the newly acquired
      information for the canine health status and prophylaxis programmes are also
      discussed.

PMID- 18635323
TI  - Dynamics of virus excretion via different routes in pigs experimentally infected
      with classical swine fever virus strains of high, moderate or low virulence.
AB  - Classical swine fever virus (CSFV) is transmitted via secretions and excretions
      of infected pigs. The efficiency and speed of the transmission depends on a
      multitude of parameters, like quantities of virus excreted by infected pigs. This
      study provides quantitative data on excretion of CSFV over time from pigs
      infected with a highly, moderately or low virulent strain. For each strain, five
      individually housed pigs were infected. Virus excretion was quantified in
      oropharyngeal fluid, saliva, nasal fluid, lacrimal fluid, faeces, urine and skin
      scraping by virus titration and quantitative Real-Time Reverse Transcription
      Polymerase Chain Reaction (qRRT-PCR). Infectious virus was excreted in all
      secretions and excretions of pigs infected with the highly and moderately
      virulent strain, while excretion from pigs infected with the low virulent strain
      was mostly restricted to the oronasal route. Pigs infected with the highly
      virulent strain excreted significantly more virus in all their secretions and
      excretions over the entire infectious period than pigs infected with the
      moderately or low virulent strains. An exception were the pigs that developed the
      chronic form of infection after inoculation with the moderately virulent strain.
      During the entire infectious period, they excreted the largest amounts of virus
      via most secretions and excretions, as they excreted virus continuously and for a
      long duration. This study highlights the crucial role chronically infected pigs
      may play in the transmission of CSFV. Furthermore, it demonstrates the importance
      of discriminating between strains and the clinical appearance of infection when
      using excretion data for modelling.

PMID- 18635324
TI  - Significance of a screening device (Apnomonitor 5) for sleep apnea syndrome.
AB  - OBJECTIVES: The objective was to evaluate the significance of a portable sleep
      monitoring device (Apnomonitor 5, Chest Co., Tokyo, Japan) to diagnose sleep
      apnea syndrome (SAS). METHODS: The Apnomonitor 5 comprised an oronasal
      thermistor, a pulse oximeter, chest and abdominal belts to monitor the
      circumferences of the chest and abdomen, a microphone to monitor tracheal sound,
      a position detector, and an integrative unit. This screening device was
      commercially available and it had been used to diagnose SAS in our country.
      Twenty-two consecutive adults who attended Inazawa City Hospital who were
      suspected for SAS were prospectively enrolled and they undertook the standard
      polysomnography (PSG) and Apnomonitor 5 simultaneously. The designated
      polysomnographers analyzed the records of the PSG and Apnomonitor 5. These sleep
      and respiratory parameters of the devices were compared, the results of which
      were double-checked by the designated sleep specialist. RESULTS: The apnea
      hypopnea index (AHI), apnea index, total number of apnea, and oxygen desaturation
      index obtained by the PSG and Apnomonitor 5 correlated significantly, whereas the
      averaged sleep time, total number of hypopnea, hypopnea index, and nadir oxygen
      saturation differed between the devices. The sensitivity of the Apnomonitor 5
      versus PSG was 95% in the SAS patients with the AHI> or =15. CONCLUSIONS: The
      Apnomonitor 5 can be a sensitive and useful screening device for SAS especially
      in patients with the AHI> or =15.

PMID- 18635325
TI  - Late complications of radiotherapy for nasopharyngeal carcinoma.
AB  - OBJECTIVE: To evaluate and assemble late complications of radiotherapy in cases
      of nasopharyngeal cancer. METHODS: From October 2003 to January 2005, a
      prospective cohort study was done in a tertiary center, Chiang Mai University
      Hospital. Two hundred patients were evaluated for late complication according to
      the RTOG/EORTC late radiation morbidity scoring criteria. RESULTS: Of 200
      patients, 131 were male (65.5%) and 69 female (34.5%). The mean age was 49.7+/
      13.5 years (11-78). The mean pre- and post-treatment body mass indexes (BMI) were
      22.5+/-4 (15-35.6), and 19.8+/-3.2 (12.9-34.5; P<0.05). Mean post-radiation
      period was 3.6+/-3.4 years (0.3-18.6 years). The radiation dosage ranged from 60
      to 76Gy (mean 69Gy). Most of the patients (92%) had undifferentiated (50.5%) and
      poorly differentiated (41.5%) squamous cell carcinoma. Eighty-eight percent of
      the patients were in Stage III and IV. Chemotherapy was given to 145 patients
      (72.5%). The mean post-radiation period in the added chemotherapy group was lower
      than the group treated with radiation alone (2.9+/-2.7 years vs. 5.4+/-4.4 years,
      P<.05). The most common complication was dryness of mouth (97.5%); followed by
      hearing impairment (inner ear 82.5%). Added chemotherapy increased the
      complication severity significantly for the skin (P<0.05). The mean number of
      complications was 6.3+/-2.2 (range from 1 to 12). CONCLUSION: In this study,
      every patient had a more or less adverse reaction to radiation. Doctors need to
      be aware of these complications in order to prevent serious ones and to improve
      the patients' quality of life in the long term.

PMID- 18635326
TI  - Experimental evaluation of relapse-risks in operated zygoma fractures.
AB  - OBJECTIVES: Prevention of relapse, or postoperative dislocation, of the fixed
      zygoma is necessary to achieve optimal results in the treatment of zygoma
      fractures. Assuming that the occurrence of intensified stresses on mastication at
      the screw-bone interface (SBI) constitutes the essential cause of the relapse, we
      evaluated the stresses for three different fixation methods-fixation at the
      frontal process (FP), inferior orbital rim (IOR), and zygomatico-maxillary
      buttress (ZMB). METHODS: We used 10 computer-aided design (CAD) models simulating
      zygoma fractures in the experiment. For each CAD model, we fixed the fractured
      zygoma with four screws and one mini-plate at the FP, IOR, or ZMB. After applying
      a 5.5kg force simulating mastication, we calculated the intensity and
      distribution patterns of the stresses occurring at the SBIs of the fixation
      screws using the finite element method. Thereby, we evaluated dynamic stability
      of the fixed zygoma for each of the three fixation methods. RESULTS: Greater
      stresses occur at the SBIs with IOR fixation than at those with FP and ZMB
      fixation. Although the stresses occurring at the SBIs on mastication demonstrated
      evenly distributed patterns with the FP and ZMB fixation, the stresses
      demonstrated concentration on one screw with the IOR fixation. CONCLUSIONS: The
      fixed zygoma is more likely to cause relapse with the IOR fixation than with the
      FP or ZMB fixation. Hence, in performing zygoma fixation at the IOR, care should
      be taken to minimize the likelihood of postoperative relapse that is caused by
      skewed distribution of the stresses on the fixation screws.

PMID- 18635327
TI  - Decompression effects of erythritol on endolymphatic hydrops.
AB  - OBJECTIVE: The effect of the uptake of erythritol with and without the addition
      of pectin on fecal condition, p-OSM and p-AVP levels, and the endolymphatic
      volume was investigated to consider the possibility that erythritol is applicable
      as a therapeutic agent for Meniere's disease. MATERIALS AND METHODS: Two
      experiments were performed using 100 female Hartley guinea pigs. Experiment 1 was
      designed to morphologically investigate the influence of the uptake of erythritol
      with or without the addition of pectin on the endolymphatic volume. Experiment 2
      was designed to investigate changes in p-OSM and p-AVP levels after the uptake of
      erythritol with or without the addition of pectin. RESULTS: (1) Endolymphatic
      hydrops significantly decreased after the uptake of a mixture of erythritol and
      pectin, but did not decrease after the uptake of pectin or erythritol (p<0.001).
      (2) The fecal condition was muddy in all animals with the uptake of erythritol
      alone, but muddy or very soft feces were not observed in animals with a mixture
      of pectin and erythritol. p-AVP and p-OSM levels were significantly elevated in
      animals with the uptake of erythritol alone or a mixture of erythritol and
      pectin. Notably, the increase in p-AVP and p-OSM levels was significantly more
      evident in animals with the uptake of erythritol alone (one-way ANOVA, p<0.001).
      CONCLUSIONS: The addition of pectin almost completely suppressed erythritol
      induced diarrhea. Consequently, the secondary elevation of p-AVP and p-OSM due to
      diarrhea was also reduced. The uptake of a mixture of erythritol and pectin
      markedly decompressed endolymphatic hydrops, although the uptake of erythritol
      alone did not. The difference of the decompression effect between animal groups
      with the uptake of erythritol alone and a mixture of erythritol and pectin seemed
      to be attributable to the difference of p-AVP levels due to diarrheal state.

PMID- 18635328
TI  - Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in
      Japanese.
AB  - OBJECTIVE: To evaluate Japanese tolerability to pilocarpine of 5 mg t.i.d.
      METHODS: From January 2006 to July 2006, 39 patients with xerostomia received 5
      mg t.i.d. pilocarpine for at least for 12 weeks unless they had experienced
      unacceptable adverse effects. All patients received radiotherapy that included
      the parotid glands in the radiation field >50 Gy. The body weights of the
      patients ranged from 42 to 73 kg (median 60 kg). RESULTS: Thirty-six of the 39
      patients were evaluable. The tolerated rate was only 47%. Of the 25 patients
      whose body weights were less than 65 kg, the tolerated rate was 36%, whereas the
      rate of the 11 patients whose body weights were 65 kg or above was 72% (p=0.050).
      The most common adverse effect was sweating with an incidence of 64%. Response
      rate, which was defined as the total number of patients with an increase of at
      least 25 mm from the baseline in the VAS score divided by the number of
      maintaining patients among those who started pilocarpine after more than 4 months
      from the start of radiotherapy, was 40% at 12 weeks (n=15). CONCLUSION: For
      Japanese, 5mg t.i.d. pilocarpine caused a high incidence of unacceptable adverse
      effects. A lower dose of pilocarpine needs to be considered.

PMID- 18635329
TI  - A comparison of rapid-scanning X-ray fluorescence mapping and magnetic resonance
      imaging to localize brain iron distribution.
AB  - The clinical diagnosis of many neurodegenerative disorders relies primarily or
      exclusively on observed behaviors rather than measurable physical tests. One of
      the hallmarks of Alzheimer disease (AD) is the presence of amyloid-containing
      plaques associated with deposits of iron, copper and/or zinc. Work in other
      laboratories has shown that iron-rich plaques can be seen in the mouse brain in
      vivo with magnetic resonance imaging (MRI) using a high-field strength magnet but
      this iron cannot be visualized in humans using clinical magnets. To improve the
      interpretation of MRI, we correlated iron accumulation visualized by X-ray
      fluorescence spectroscopy, an element-specific technique with T1, T2, and
      susceptibility weighted MR (SWI) in a mouse model of AD. We show that SWI best
      shows areas of increased iron accumulation when compared to standard sequences.

PMID- 18635330
TI  - Generalized diffraction enhanced imaging: application to tomography.
AB  - A simple generalization of the diffraction enhanced imaging (DEI) technique,
      called generalized DEI (GDEI), and its application to tomographic imaging are
      herein presented. In planar imaging, the GDEI algorithm combines three input
      images (acquired at different analyzer positions) to deliver three parametric
      images, providing information respectively on absorptive, refractive and ultra
      small-angle scattering features of the sample. The application of the same
      algorithm in computed tomography (CT-GDEI), acquiring three tomographic datasets
      at different analyzer positions, is formally justified. Experimental tests have
      been conducted at the SYRMEP beamline of ELETTRA (Trieste, Italy) by means of
      custom phantoms, featuring absorption, refraction and ultra-small-angle
      scattering. The results show that CT-GDEI provides a simple way to map the
      information relative to the three effects in three parametric tomographic images.

PMID- 18635331
TI  - Enhancement of survival of 9L gliosarcoma bearing rats following intracerebral
      delivery of drugs in combination with microbeam radiation therapy.
AB  - Microbeam radiation therapy (MRT) is a form of radiosurgery first dedicated to
      the treatment of brain tumors. It uses arrays of synchrotron generated X-rays
      microbeams of very high doses (typically 625 Gy). Microbeams are typically few
      micrometers large (25 microm) and few hundred micrometers spaced (200 microm).
      Previous experiments have shown that despite a good tumor eradication rate
      (5/11), a 100-microm spacing unidirectional irradiation (skin dose 625 Gy, width
      25 microm) was too invasive for normal tissue. On the contrary, a 200-microm
      spacing unidirectional irradiation preserved healthy tissue with a low tumor
      eradication rate (2/32). The purpose of this study was to enhance the potential
      of the 200 microm spacing irradiation protocol. After diagnosis of the tumor by
      MRI, 9L tumor-bearing rats were laterally irradiated with 51 microbeams (625 Gy,
      25 microm, 200 microm) 14 days after implantation. Three drugs (Gd-DTPA, CisPt,
      temozolomide) were tested, after intratumoral injection at the theoretical center
      of the tumor. Control rats displayed a median survival time of 19 days. There was
      no significant difference between drug-treated rats and control group. Irradiated
      animals showed an increase in life span (ILS) of 60.5%. Interestingly, the ILS
      increased to 131.6% and 1/6 rat survived more than 1 year in case of MRT combined
      with gadolinium injection. These results showed that the synergy between
      gadolinium injection (acting as a dose enhancer) and MRT improved significantly
      the life span of tumor bearing rats (more than a factor 2).

PMID- 18635332
TI  - Separation of quercetin, sexangularetin, kaempferol and isorhamnetin for
      simultaneous HPLC determination of flavonoid aglycones in inflorescences, leaves
      and fruits of three Sorbus species.
AB  - A reversed-phase high-performance liquid chromatographic (RP-HPLC) method was
      developed and validated for the simultaneous determination of four flavonol
      aglycones (quercetin, QU; sexangularetin, SX; kaempferol, KA; isorhamnetin, IS)
      in hydrolyzed extracts from different plant parts of Sorbus aucuparia L., Sorbus
      aria (L.) Crantz. and Sorbus intermedia (Ehrh.) Pers. Separation of the four
      compounds was accomplished on a C18 Lichrosphere 100 column (5 microm, 250 mm x
      4.6mm, i.d.) with a methanol gradient elution and recorded at 370 nm. The high
      resolution of critical bands - SX, KA and IS - was achieved with retention of the
      last peak (IS) in 19.5 min. The equilibration of the standard mixture by addition
      of HCl to an acid concentration equal that of hydrolyzed extracts injected was
      found to be necessary when minimizing calibration error. The correlation
      coefficients of all the calibration curves showed good linearity (r>0.9991) over
      the test range. The relative standard deviation of the method was less than 2.8%
      for intra- and inter-day assays, and the average recoveries were between 95.5 and
      102.5%. High sensitivity was demonstrated with detection limits between 0.050 and
      0.085 microg/ml. The level of total aglycones was found to be in the range of 687
      1,515 mg/100g of dry weight in the inflorescences, 424-1,078 mg/100g in the
      leaves and 20-60 mg/100g in the fruits depending on the Sorbus species.

PMID- 18635333
TI  - Polypill for the treatment of cardiovascular diseases part 2. LC-MS/TOF
      characterization of interaction/degradation products of atenolol/lisinopril and
      aspirin, and mechanisms of formation thereof.
AB  - A polypill for cardiovascular diseases (CVD) is under development. It is proposed
      to contain a combination of antithrombotic agent (aspirin), low-dose blood
      pressure lowering agents, i.e., angiotensin-converting enzyme inhibitor
      (lisinopril), one among a beta-blocker (atenolol) or diuretic
      (hydrochlorothiazide), and a statin (simvastatin/atorvastatin/pravatsatin, etc.).
      Due to the presence of multiple drugs in the same formulation, there is a strong
      likelihood of interaction among the drugs and/or their products. In a previous
      study, we observed formation of a number of interaction/degradation products from
      atenolol and lisinopril in the presence of aspirin. Accordingly, the purpose of
      this study was to characterize the resolved products using high resolution mass
      spectrometric and fragmentation analyses using a LC-MS/TOF system. Initially,
      studies were carried out on the drugs (atenolol, lisinopril and aspirin) to
      establish their complete fragmentation pattern. These studies were then extended
      to degraded samples to postulate the structures of interaction/degradation
      products. The characterized structures were justified through mechanistic
      explanations.

PMID- 18635334
TI  - IGF-I- and EGF-dependent DNA synthesis of porcine myoblasts is influenced by the
      dietary isoflavones genistein and daidzein.
AB  - Soy-derived isoflavones have been reported to be specific inhibitors of protein
      tyrosine kinases like the type 1 insulin-like growth factor receptor (IGF-1R) and
      the epidermal growth factor receptor (EGFR). This study was conducted to
      investigate, whether IGF-I and EGF stimulate porcine myoblast growth and whether
      the responses are influenced by isoflavones. Satellite cell-born myoblasts
      derived from the semimembranosus muscle of newborn piglets were treated for 26 h
      with IGF-I or EGF alone and in combination with genistein or daidzein. The DNA
      amount was measured and DNA synthesis was recorded as 6 h-[(3)H]thymidine
      incorporation during exponential growth in serum-free basal medium. IGF-I and EGF
      synergistically stimulated DNA synthesis of porcine myoblast with EGF causing a
      greater response. Genistein (100 micromol/l) effectively reduced the growth
      factor-mediated DNA synthesis, which was associated with an inhibition of growth
      factor receptor protein expression. In response to daidzein no reduction in
      growth factor-mediated DNA synthesis was found. Daidzein (1; 10 micromol/l)
      combined with IGF-I caused even a slight increase in DNA amount compared with the
      untreated control. The expression of the IGF-1R precursor protein was reduced
      with 10 and 100 micromol/l daidzein, whereas the EGFR expression remained
      unchanged with daidzein. The results suggest that dietary isoflavones may
      interact with growth factor-induced stimulation of pig skeletal muscle growth.

PMID- 18635335
TI  - The Powerlink system for endovascular abdominal aortic aneurysm repair: six-year
      results.
AB  - OBJECTIVE: We compared the results of endovascular repair using the Powerlink
      endovascular graft with conventional open abdominal aortic aneurysm repair
      through a 6-year follow-up period. METHODS: Two hundred fifty-eight patients with
      abdominal aortic aneurysms were prospectively enrolled in a multicenter trial and
      underwent endovascular repair (N = 192) or conventional open surgery (N = 66).
      All endovascular repairs were approached through a surgically exposed femoral
      artery and a percutaneously accessed femoral artery. Study endpoints included all
      cause mortality and morbidity. Follow-up imaging consisted of contrast-enhanced
      CT scans and plain abdominal x-rays at 1, 6, 12 months, and annually
      postoperatively. RESULTS: Technical success was achieved in 97.9% of test
      patients, with four failed insertions (three early conversions because of
      deployment issues, one access failure). Mean follow-up was 4.1 +/- 1.7 years
      (test group) and 3.1 +/- 1.9 years (control group). Perioperative morbidity and
      mortality were significantly reduced in the test group compared with the control
      group (P < .05). At 6 years, all-cause mortality and morbidity was no different
      in the Powerlink group compared with the open repair group. There were no
      reported stent fractures, graft disruptions, or aneurysm ruptures. Core
      laboratory-reported endoleaks included proximal or distal type I (n = 1) and type
      I/II (n = 3), with no type III or type IV endoleaks. One explant (0.5%) was
      undertaken to resolve a refractory type I endoleak. A total of 37 secondary
      procedures were performed in 26 patients to treat site-reported endoleak (n = 26;
      7 for type I and 19 for type II), graft limb occlusion (n = 7), native artery
      occlusion (n = 3), or endograft migration (n = 1). A reduction in mean aneurysm
      sac diameters and volumes has been noted at every follow-up interval. CONCLUSION:
      Consistent with other reports, perioperative morbidity and mortality were
      significantly reduced in the endovascular group compared with the open repair
      group. Six-year follow-up of patients treated with the Powerlink system
      demonstrates the continued safety and efficacy of its treatment of abdominal
      aortic aneurysm.

PMID- 18635336
TI  - Inhibition of inflammatory mediator secretion by (-)-DHMEQ in mouse bone marrow
      derived macrophages.
AB  - Previously, we designed and synthesized a new NF-kappaB inhibitor,
      dehydroxymethylepoxyquinomicin (DHMEQ), and found that racemic DHMEQ inhibited
      cytokine secretion and phagocytosis by cells of the macrophage cell line
      RAW264.7. In the present research, we looked into the effect of optically active
      (-)-DHMEQ on the NO production, inflammatory cytokine secretion, and
      prostaglandin secretion in mouse bone marrow-derived macrophages (BMMs). We also
      studied the effect of (-)-DHMEQ on the differentiation of macrophages. DHMEQ
      inhibited lipopolysaccharide (LPS)-induced NF-kappaB activation. It also
      inhibited the expression of inducible NO synthase (iNOS) and NO production
      induced by LPS. Using enzyme-linked immunosorbent assays, we showed DHMEQ to
      inhibit LPS-induced secretion of IL-6 and TNF-alpha. It also inhibited COX-2
      expression and prostaglandin E(2) production and secretion. It did not inhibit
      the phagocytosis of fluorescently labeled Escherichia coli by BMMs treated with
      LPS, unlike in the case of RAW264.7 cells. Next we examined the effect of the
      inhibitor on M-CSF-induced differentiation of bone marrow cells to macrophages.
      DHMEQ showed no effect on the differentiation in terms of reactive oxygen species
      production and F4/80 expression. However, although BMM incorporated oxidized LDL
      to give rise to foam cells, the (-)-DHMEQ-treated bone marrow cells did not take
      up oxidized LDL. Taken together, our data show that (-)-DHMEQ inhibited LPS
      induced activation of BMM in terms of NO and cytokine secretion, but its effect
      on phagocytosis differed between BMMs and RAW264.7 cells. We also found that the
      functional differentiation into macrophages was inhibited by (-)-DHMEQ.

PMID- 18635337
TI  - [Localised relapse of orbital embryonal rhabdomyosarcoma].

PMID- 18635338
TI  - Neuropsychological measures probably facilitate heritability research of ADHD.
AB  - Previous studies, in which cognitive and motor neuropsychological tasks were
      administered to 816 children from Attention-Deficit/Hyperactivity Disorder (ADHD)
      and control-families, showed that various of these measures appeared useful for
      genetic research in ADHD by forming candidate endophenotypes: underlying,
      heritable, vulnerability traits that mark an enhanced liability for developing
      ADHD. The current study extends these findings by showing that six of these ten
      measures correlate more strongly between siblings than an ADHD composite,
      suggesting these measures may have a larger heritability than ADHD itself.
      Significant sibling cross-correlations also suggested that six of ten
      neuropsychological measures related to similar familial (and heritable) factors
      as ADHD, suggesting these measures to be useful for ADHD genetic research. An
      aggregated neuropsychological composite appeared to be the most powerful, since
      it correlated more strongly between siblings than most individual task measures.
      These findings suggest heritability research in ADHD will probably be facilitated
      by including neuropsychological measures.

PMID- 18635339
TI  - Prospective memory and its correlates and predictors in schizophrenia: an
      extension of previous findings.
AB  - BACKGROUND: Prospective memory (PM) is the ability to remember to do something in
      the future without explicit prompts. Extending the number of subjects and the
      scope of our previously published study, this investigation examined the
      relationship between PM and socio-demographic and clinical factors, activities of
      daily living (ADL) and frontal lobe functions in patients with chronic
      schizophrenia. METHODS: One hundred and ten Chinese schizophrenia patients, 60
      from the previous study and 50 additional patients recruited for this study, and
      110 matched healthy comparison subjects (HC) formed the study sample. Patients'
      clinical condition and activity of daily living were evaluated with the Brief
      Psychiatric Rating Scale (BPRS) and the Functional Needs Assessment (FNA). Time-
      and event-based PM tasks and three tests of prefrontal lobe functions (Design
      Fluency Test [DFT], Tower of London [TOL], Wisconsin Card Sorting Test [WCST])
      were also administered. RESULTS: Patients' level of ADL and psychopathology were
      not associated with PM functions and only anticholinergic medications (ACM)
      showed a significant negative correlational relationship with PM tasks.
      Confirming the findings of the previous study, patients performed significantly
      more poorly on all two PM tasks than HC. Performance on time-based PM task
      significantly correlated with age, education level and DFT in HC and with age,
      DFT, TOL and WCST in patients. Patients' performance on the event-based PM
      correlated with DFT and one measure of WCST. In patients, TOL and age predicted
      the performance on time-based PM task; DFT and WCST predicted the event-based
      task. CONCLUSIONS: Involving a large sample of patients with matched controls,
      this study confirmed that PM is impaired in chronic schizophrenia. Deficient PM
      functions were related to prefrontal lobe dysfunction in both HC and patients but
      not to the patients' clinical condition, nor did they significantly affect ADL.
      ACMs determined certain aspects of PM.

PMID- 18635340
TI  - 1-year follow-up study of cognitive function in first-episode non-affective
      psychosis.
AB  - The longitudinal course of primary cognitive dysfunction seen in schizophrenia
      has yet to be fully clarified. Whereas some studies in chronic patients have
      revealed a progressive decline in cognitive abilities, those studies with first
      episode patients have indicated that initial cognitive deficits might remain
      stable over time. The aim of this study was to examine the longitudinal course of
      cognitive functioning in patients with a first episode of schizophrenia. 112
      patients with a first episode of schizophrenia-spectrum disorders and 22 healthy
      controls completed clinical and cognitive evaluations at baseline and again after
      1 year. An extensive neuropsychological battery that comprised seven cognitive
      domains was used. Patients and controls improved their cognitive performance in
      virtually all the cognitive domains after one year. However, patients continued
      to show marked cognitive deficits after one year, unlike healthy volunteers. The
      longitudinal cognitive changes were similar in patients and controls in all
      domains except Verbal Memory (F = 11.67; df = 1; P = 0.001). The increase in
      cognitive scores found during early phases of the illness seems to be associated
      to practice-related changes and would not reflect a real cognitive enhancement
      but rather stability of deficit. Patients' deficits remained stable over time in
      all cognitive domains except Verbal Memory, in which less performance improvement
      was found. Further investigations are warranted to discern the variability in
      patterns of specific cognitive deficits over time.

PMID- 18635341
TI  - Linezolid for the treatment of infections caused by Gram-positive pathogens in
      China.
AB  - In this randomised, double-blind, comparator-controlled, multicentre study
      conducted in China, 142 hospitalised patients aged 18-75 years with pneumonia
      (n=80) or complicated skin and soft-tissue infection (cSSTI) (n=62) due to
      suspected or known Gram-positive pathogens were randomised (1:1) to receive
      either linezolid 600mg (n=71) or vancomycin 1g in patients aged < or =60 years or
      0.75g in patients aged >60 years (n=71) intravenously every 12h. The duration of
      treatment was 10-21 days for patients with pneumonia and 7-21 days for patients
      with cSSTI. Clinical outcomes were assessed at end-of-treatment (EOT) visit and
      follow-up (FU) visit 7-28 days post therapy. Staphylococcus aureus was the most
      common pathogen at baseline and most of these isolates were resistant to
      meticillin. All isolates were susceptible to linezolid and vancomycin. For the
      evaluable patients, the effective treatment rate for linezolid was higher than
      that for vancomycin at EOT (86.9% (53/61) vs. 61.7% (37/60)) and at FU (83.1%
      (49/59) vs. 64.9% (37/57)). Pathogen eradication rates for the microbiologically
      evaluable patients at FU were 79.2% (42/53) for linezolid and 61.5% (32/52) for
      vancomycin. The incidence of drug-related adverse events (AEs) was 25.4% (18/71)
      for linezolid and 16.9% (12/71) for vancomycin. Four (5.6%) linezolid-treated and
      eight (11.3%) vancomycin-treated patients discontinued the study drug because of
      an AE. Linezolid was well tolerated and effective for the treatment of infections
      caused by Gram-positive pathogens, including meticillin-resistant S. aureus.

PMID- 18635342
TI  - Neural correlates of attachment trauma in borderline personality disorder: a
      functional magnetic resonance imaging study.
AB  - Functional imaging studies have shown that individuals with borderline
      personality disorder (BPD) display prefrontal and amygdala dysfunction while
      viewing or listening to emotional or traumatic stimuli. The study examined for
      the first time the functional neuroanatomy of attachment trauma in BPD patients
      using functional magnetic resonance imaging (fMRI) during the telling of
      individual stories. A group of 11 female BPD patients and 17 healthy female
      controls, matched for age and education, told stories in response to a validated
      set of seven attachment pictures while being scanned. Group differences in
      narrative and neural responses to "monadic" pictures (characters facing
      attachment threats alone) and "dyadic" pictures (interaction between characters
      in an attachment context) were analyzed. Behavioral narrative data showed that
      monadic pictures were significantly more traumatic for BPD patients than for
      controls. As hypothesized BPD patients showed significantly more anterior
      midcingulate cortex activation in response to monadic pictures than controls. In
      response to dyadic pictures patients showed more activation of the right superior
      temporal sulcus and less activation of the right parahippocampal gyrus compared
      to controls. Our results suggest evidence for potential neural mechanisms of
      attachment trauma underlying interpersonal symptoms of BPD, i.e. fearful and
      painful intolerance of aloneness, hypersensitivity to social environment, and
      reduced positive memories of dyadic interactions.

PMID- 18635343
TI  - Combination of (13)C-(13)C COSY and DARR (COCODARR) in solid-state NMR.
AB  - In this work, we describe a new 2D (13)C-(13)C correlation experiment in solids,
      in which (13)C-(13)C J-correlation (COSY) and dipolar correlation (DARR) are
      recorded at the same time. The sequence is similar to COCONOSY in the liquid
      state NMR, in which (1)H-(1)H COSY and NOESY spectra are obtained in a single
      experiment. The combined COSY and DARR experiment facilitates assignment of (13)C
      signals in solids.

PMID- 18635344
TI  - Effect of molecular weight on the dermatopharmacokinetics and systemic
      disposition of drugs after intracutaneous injection.
AB  - The aim of this study was to investigate the effect of molecular weight on the
      topical migration and systemic absorption of drugs, sodium salicylate (SA),
      calcein sodium (CAL) and FITC-dextrans (FD-4, FD-10, FD-20 and FD-40), after
      intracutaneous (i.c.) injection. The apparent diffusion coefficients in the skin
      (D(s)) of SA, CAL and FD-4 after i.c. injection were almost the same and slightly
      less than 1x10(-4)cm(2)/min. The D(s) value drastically decreased with molecular
      weight more than 10kDa. The plasma concentration-time curve after i.c. injection
      was predicted by the convolution method. The ratio of AUC (observed/predicted)
      was approximately unity for SA, CAL and FD-4 although the systemic absorption of
      only FD-4 was delayed. In contrast, the AUC ratios of FD-10, FD-20 and FD-40 were
      about 0.5, 0.2 and 0.06, respectively, and obviously decreased with the molecular
      weight. The elimination of FD-10, FD-20 and FD-40 from the skin was slow and the
      drugs tended to remain in the muscle. These results indicated the importance of
      diffusion in the skin and permeability through the blood vessels for local
      migration and systemic absorption of drugs after penetration into viable skin.

PMID- 18635345
TI  - Outcome of patients with idiopathic pulmonary fibrosis (IPF) ventilated in
      intensive care unit.
AB  - Idiopathic pulmonary fibrosis (IPF) is the commonest cause of interstitial lung
      disease. Till date there is no proven successful treatment. The prognosis is poor
      with a median survival of 3 years. Patients with IPF presented with acute
      respiratory failure are often referred to the intensive care unit for ventilatory
      support. Available data showed that outcome of these patients is very poor and
      mechanical ventilation is mostly futile. Patients and their families should be
      informed about the prognosis, outcome and overall outlook before making decision
      about ventilation and organ support. Available outcome data should be used to
      develop institutional and professional guidelines to help in making these
      difficult decisions.

PMID- 18635346
TI  - Asthma mortality among Swedish children and young adults, a 10-year study.
AB  - BACKGROUND: Previous reports indicate that morbidity and mortality from asthma
      have increased during the past decades. Here, the mortality rate associated with
      asthma and possible risk factors in children and young adults in Sweden during
      the period 1994-2003 were evaluated. METHODS: The medical profession was asked to
      report suspected cases of death from asthma in individuals 1-34 years of age. All
      death certificates containing relevant ICD codes were reviewed. Medical records
      and autopsy reports were assessed and telephone interviews with next-of-kin
      performed. RESULTS: During the 10-year period 37 deaths due to asthma were
      identified. The median age at the time of death was 27 years and 6 of the
      deceased were younger than 15. The overall incidence of death from asthma
      decreased from 1.54 deaths per million in 1994 to 0.53 per million in 2003.
      Common risk factors were under-treatment (23/37), poor adherence to prescribed
      treatment (17/37) and adverse psychosocial situation (19/37). An alarming finding
      was that 11 of the 37 deaths were probably caused by food allergy and for 8
      subjects death was associated with exposure to pet dander. The death certificates
      were found to contain inaccuracies with 30% of those for whom asthma was reported
      as the underlying cause having died from other causes. CONCLUSION: Asthma
      mortality in children and young adults in Sweden decreased between 1994 and 2003.
      Food allergy and inadequate treatment were the major risk factors for such a
      death. Recognition and special care of patients with asthma who have shown signs
      of non-compliance, denial or severe food allergy must be encouraged.

PMID- 18635347
TI  - Optically induced flow cytometry for continuous microparticle counting and
      sorting.
AB  - This paper reports a new microfluidic device capable of performing optically
      induced flow cytometry (OIFC). This enables it to continuously count and to sort
      microparticles based on optically induced dielectrophoretic (ODEP) forces.
      Gravity was used to drive the particles instead of using syringe pumps. The
      particles were then focused inside a sample channel by the ODEP forces and then
      passed through a detection region. A pair of optical fibers were embedded into
      fiber channels to count the number of particles and analyze the particle size in
      real time. Using 20.9 and 9.7 microm polystyrene microparticles, the average
      light intensity were about 63.67 and 8.80 units, with a coefficient-of-variation
      (CV) of 7.46 and 25.57%, respectively. This demonstrated that these two particle
      sizes could be successfully distinguished. After detecting the number and size of
      the microparticles, an optically induced dynamic switch (ODS) was used to sort
      microparticles to downstream fluidic outlets. The ODS used ODEP forces generated
      by different illumination intensities or optical line widths. The ODS was
      composed of two virtual electrodes which controlled particle movement in two
      dimensions. The ODS can successfully sort microparticles with different sizes
      continuously. The development of the OIFC device is a major advancement in the
      design of microparticle counting and sorting devices. Applications in future
      biomedical applications for cell counting and manipulation are envisioned.

PMID- 18635348
TI  - A microfluidic cell array with individually addressable culture chambers.
AB  - Microfluidic arrays of living cells have raised a lot of interests recently due
      to their potential for high throughput screening of cell-based assays. This
      report presents a microfluidic cell array with individually addressable chambers
      controlled by pneumatic valves for cell culture and treatment. There are two
      modes for the cell array to be operated. In the first mode, different groups of
      cells are directed into designated chambers for culturing and observation. We
      demonstrate the delivery and culture of enhanced green fluorescent protein (EGFP)
      expressing and nonfluorescent Chinese hamster ovary (CHO) cells into specific
      chambers in the array. In the second mode, the chambers are first seeded with the
      same cell type and different reagents are delivered to specific chambers for cell
      treatment. We treat cells in designated chambers with Calcein AM and CellTrace
      calcein red-orange AM to demonstrate the principle. We envision that this
      microfluidic cell array technology will pave the way to automated high-throughput
      screening of biomolecules and drugs based on observing cellular phenotypes and
      responses.

PMID- 18635349
TI  - Structure-activity relationship studies on vitamin D lactam derivatives as
      vitamin D receptor antagonist.
AB  - Structure-activity relationship studies on 1alpha,25-dihydroxyvitamin D(3)-26,23
      lactams (DLAMs), antagonists of vitamin D, were conducted, focusing on the
      substituents of the phenyl group. One of the derivatives (23S,25S)-DLAM-1P
      3,5(OEt)(2), showed potent antagonistic activity with an IC(50) of 90nM.

PMID- 18635350
TI  - Bmi1 regulates stem cells and proliferation and differentiation of committed
      cells in mammary epithelium.
AB  - PolycombGroup (PcG) proteins are epigenetic silencers involved in maintaining
      cellular identity, and their deregulation can result in cancer [1]. Mice without
      the PcG gene Bmi1 are runted and suffer from progressive loss of hematopoietic
      and neural stem cells [2-4]. Here, we assess the effects of Bmi1 on stem cells
      and differentiation of an epithelial tissue in vivo. We chose the mammary gland
      because it allows limiting dilution transplantations [5, 6] and because Bmi1 is
      overexpressed in breast cancer [7, 8]. Our analyses show that Bmi1 is expressed
      in all cells of the mouse mammary gland and is especially high in luminal cells.
      Loss of Bmi1 results in a severe mammary-epithelium growth defect, which can be
      rescued by codeletion of the Ink4a/Arf locus or pregnancy. Even though mammary
      stem cells are present in the absence of Bmi1, their activity is reduced, and
      this is only partially due to Ink4a/Arf expression. Interestingly, loss of Bmi1
      causes premature lobuloalveolar differentiation, whereas overexpression of Bmi1
      inhibits lobuloalveolar differentiation induced by pregnancy hormones. Because
      Bmi1 affects not only mammary stem cells but also more committed cells, our data
      warrant a more detailed analysis of the different roles of Bmi1 in breast-cancer
      etiology.

PMID- 18635351
TI  - Distinct face-processing strategies in parents of autistic children.
AB  - In his original description of autism, Kanner [1] noted that the parents of
      autistic children often exhibited unusual social behavior themselves, consistent
      with what we now know about the high heritability of autism [2]. We investigated
      this so-called Broad Autism Phenotype in the parents of children with autism, who
      themselves did not receive a diagnosis of any psychiatric illness. Building on
      recent quantifications of social cognition in autism [3], we investigated face
      processing by using the "bubbles" method [4] to measure how viewers make use of
      information from specific facial features in order to judge emotions. Parents of
      autistic children who were assessed as socially aloof (N = 15), a key component
      of the phenotype [5], showed a remarkable reduction in processing the eye region
      in faces, together with enhanced processing of the mouth, compared to a control
      group of parents of neurotypical children (N = 20), as well as to nonaloof
      parents of autistic children (N = 27, whose pattern of face processing was
      intermediate). The pattern of face processing seen in the Broad Autism Phenotype
      showed striking similarities to that previously reported to occur in autism [3]
      and for the first time provides a window into the endophenotype that may result
      from a subset of the genes that contribute to social cognition.

PMID- 18635352
TI  - Condensin-dependent rDNA decatenation introduces a temporal pattern to chromosome
      segregation.
AB  - The chromosomal condensin complex gives metaphase chromosomes structural
      stability. In addition, condensin is required for sister-chromatid resolution
      during their segregation in anaphase [1-7]. How condensin promotes chromosome
      resolution is poorly understood. Chromosome segregation during anaphase also
      fails after inactivation of topoisomerase II (topo II), the enzyme that removes
      catenation between sister chromatids left behind after completion of DNA
      replication [8, 9]. This has led to the proposal that condensin promotes DNA
      decatenation [3, 10, 11], but direct evidence for this is missing and alternative
      roles for condensin in chromosome resolution have been suggested [12-14]. Using
      the budding-yeast rDNA as a model, we now show that anaphase bridges in a
      condensin mutant are resolved by ectopic expression of a foreign (Chlorella
      virus) but not endogenous topo II. This suggests that catenation prevents sister
      rDNA segregation but that yeast topo II is ineffective in decatenating the locus
      without condensin. Condensin and topo II colocalize along both rDNA and
      euchromatin, consistent with coordination of their activities. We investigate the
      physiological consequences of condensin-dependent rDNA decatenation and find that
      late decatenation determines the late segregation timing of this locus during
      anaphase. Regulation of decatenation therefore provides a means to fine tune the
      segregation timing of chromosomes in mitosis.

PMID- 18635353
TI  - Brain plasticity in the adult: modulation of function in amblyopia with rTMS.
AB  - Amblyopia is a cortically based visual disorder caused by disruption of vision
      during a critical early developmental period. It is often thought to be a largely
      intractable problem in adult patients because of a lack of neuronal plasticity
      after this critical period [1]; however, recent advances have suggested that
      plasticity is still present in the adult amblyopic visual cortex [2-6]. Here, we
      present data showing that repetitive transcranial magnetic stimulation (rTMS) of
      the visual cortex can temporarily improve contrast sensitivity in the amblyopic
      visual cortex. The results indicate continued plasticity of the amblyopic visual
      system in adulthood and open the way for a potential new therapeutic approach to
      the treatment of amblyopia.

PMID- 18635354
TI  - Sex-specific fitness effects of nutrient intake on reproduction and lifespan.
AB  - Diet affects both lifespan and reproduction [1-9], leading to the prediction that
      the contrasting reproductive strategies of the sexes should result in sex
      specific effects of nutrition on fitness and longevity [6, 10] and favor
      different patterns of nutrient intake in males and females. However, males and
      females share most of their genome and intralocus sexual conflict may prevent sex
      specific diet optimization. We show that both male and female longevity were
      maximized on a high-carbohydrate low-protein diet in field crickets Teleogryllus
      commodus, but male and female lifetime reproductive performances were maximized
      in markedly different parts of the nutrient intake landscape. Given a choice,
      crickets exhibited sex-specific dietary preference in the direction that
      increases reproductive performance, but this sexual dimorphism in preference was
      incomplete, with both sexes displaced from the optimum diet for lifetime
      reproduction. Sexes are, therefore, constrained in their ability to reach their
      sex-specific dietary optima by the shared biology of diet choice. Our data
      suggest that sex-specific selection has thus far failed fully to resolve
      intralocus sexual conflict over diet optimization. Such conflict may be an
      important factor linking nutrition and reproduction to lifespan and aging.

PMID- 18635355
TI  - Tactile rivalry demonstrated with an ambiguous apparent-motion quartet.
AB  - When observers view ambiguous visual stimuli, their perception will often
      alternate between the possible interpretations, a phenomenon termed perceptual
      rivalry [1]. To induce perceptual rivalry in the tactile domain, we developed a
      new tactile illusion, based on the visual apparent-motion quartet [2]. Pairs of
      200 ms vibrotactile stimuli were applied to the finger pad at intervals separated
      by 300 ms. The location of each successive stimulus pair alternated between the
      opposing diagonal corners of the approximately 1 cm(2) stimulation array. This
      stimulation sequence led all participants to report switches between the
      perception of motion traveling either up and down or left and right across their
      fingertip. Adaptation to tactile stimulation biased toward one direction caused
      subsequent ambiguous stimulation to be experienced in the opposing direction. In
      contrast, when consecutive trials of ambiguous stimulation were presented, motion
      was generally perceived in the direction consistent with the motion reported in
      the previous trial. Voluntary eye movements induced shifts in the tactile
      perception toward a motion axis aligned along a world-centered coordinate frame.
      Because the tactile quartet results in switching perceptual states despite
      unvaried sensory input, it is ideally suited to future studies of the neural
      processes associated with conscious tactile perception.

PMID- 18635356
TI  - PIP3-independent activation of TorC2 and PKB at the cell's leading edge mediates
      chemotaxis.
AB  - BACKGROUND: Studies show that high phosphotidylinositol 3,4,5-trisphosphate
      (PIP(3)) promotes cytoskeletal rearrangements and alters cell motility and
      chemotaxis, possibly through activation of protein kinase Bs (PKBs). However,
      chemotaxis can still occur in the absence of PIP(3), and the identities of the
      PIP(3)-independent pathways remain unknown. RESULTS: Here, we outline a PIP(3)
      independent pathway linking temporal and spatial activation of PKBs by Tor
      complex 2 (TorC2) to the chemotactic response. Within seconds of stimulating
      Dictyostelium cells with chemoattractant, two PKB homologs, PKBA and PKBR1,
      mediate transient phosphorylation of at least eight proteins, including Talin,
      PI4P 5-kinase, two Ras GEFs, and a RhoGap. Surprisingly, all of the substrates
      are phosphorylated with normal kinetics in cells lacking PI 3-kinase activity.
      Cells deficient in TorC2 or PKB activity show reduced phosphorylation of the
      endogenous substrates and are impaired in chemotaxis. The PKBs are activated
      through phosphorylation of their hydrophobic motifs via TorC2 and subsequent
      phosphorylation of their activation loops. These chemoattractant-inducible events
      are restricted to the cell's leading edge even in the absence of PIP(3).
      Activation of TorC2 depends on heterotrimeric G protein function and intermediate
      G proteins, including Ras GTPases. CONCLUSIONS: The data lead to a model where
      cytosolic TorC2, encountering locally activated small G protein(s) at the leading
      edge of the cell, becomes activated and phosphorylates PKBs. These in turn
      phosphorylate a series of signaling and cytoskeletal proteins, thereby regulating
      directed migration.

PMID- 18635357
TI  - ced-4 and proto-oncogene tfg-1 antagonistically regulate cell size and apoptosis
      in C. elegans.
AB  - BACKGROUND: Cell-size-control systems, coupled with apoptotic- and cell
      proliferation-regulatory mechanisms, determine the overall dimensions of organs
      and organisms, and their dysregulation can lead to tumor formation. The
      interrelationship between cell-growth-regulatory mechanisms and apoptosis during
      normal development and cancer is not understood. The TRK-fused gene (TFG)
      promotes tumorigenesis when present in chromosomal rearrangements from various
      human-cancer types by unknown mechanisms. Apaf1/CED-4 is essential for apoptosis
      but has not been shown to function in cell-growth control. RESULTS: We found that
      loss of TFG-1, the TFG ortholog in Caenorhabditis elegans, results in
      supernumerary apoptotic corpses, whereas its overexpression is sufficient to
      inhibit developmentally programmed cell death. TFG-1 is also required for cells
      and nuclei to grow to normal size. Furthermore, we found that CED-4 is required
      for cell-growth inhibition in animals lacking TFG-1. However, caspases, the
      downstream effectors of CED-4-mediated apoptosis, are not required in TFG-1- or
      CED-4-regulated cell-size control. CED-4 acts to inhibit cell growth by
      antagonizing the effects of other conserved cell-size-regulating proteins,
      including cAMP response element binding (CREB) protein, translation-initiation
      factor eIF2B, and the nucleolar p53-interacting protein nucleostemin.
      CONCLUSIONS: These findings show that TFG-1 suppresses apoptosis and is essential
      for normal cell-size control, suggesting that abnormalities in the cell-growth
      promoting and apoptosis-inhibiting functions of TFG might be responsible for its
      action in tumorigenesis. Also, they reveal that CED-4 plays a pivotal role in
      activating apoptosis and restricting cell and nuclear size, thereby determining
      the appropriate overall size of an animal. Thus, these findings reveal links
      between the control mechanisms for apoptosis and cell growth.

PMID- 18635359
TI  - Necrotic cell death and 'necrostatins': now we can control cellular explosion.
AB  - The receptor-interacting protein 1 (RIP1) kinase activity is necessary for death
      receptor-induced necrotic cell death. Recently, it has been demonstrated that
      'necrostatins' efficiently block tumor necrosis factor-induced necrotic cell
      death through the inhibition of RIP1 kinase activity. This discovery supports the
      concept that receptor-induced necrosis, just like apoptosis, is a controlled
      cellular process. In addition, necrostatins are becoming important tools for
      evaluating the contribution of necrotic cell death in experimental disease
      models.

PMID- 18635358
TI  - Complementary adhesin function in C. albicans biofilm formation.
AB  - BACKGROUND: Biofilms are surface-associated microbial communities with
      significant environmental and medical impact. Here, we focus on an adherence
      mechanism that permits biofilm formation by Candida albicans, the major invasive
      fungal pathogen of humans. RESULTS: The Als surface-protein family has been
      implicated in biofilm formation, and we show that Als1 and Als3 have critical but
      redundant roles. Overexpression of several other Als proteins permits biofilm
      formation in a biofilm-defective als1/als1 als3/als3 strain, thus arguing that
      the function of Als proteins in this process is governed by their respective
      expression levels. The surface protein Hwp1 is also required for biofilm
      formation, and we find that a mixture of biofilm-defective hwp1/hwp1 and
      als1/als1 als3/als3 strains can form a hybrid biofilm both in vitro and in vivo
      in a catheter infection model. Complementary function of Hwp1 and Als1 and 3
      seems to reflect their interaction because expression of Hwp1 in the heterologous
      host S. cerevisiae permits adherence to wild-type C. albicans, but not to an
      als1/als1 als3/als3 strain. CONCLUSIONS: The complementary roles of Hwp1 and Als1
      and Als3 in biofilm formation are analogous to the roles of sexual agglutinins in
      mating reactions. This analogy suggests that biofilm-adhesin complementarity may
      promote formation of monospecies biofilms.

PMID- 18635360
TI  - Precision assessment of model-based RSA for a total knee prosthesis in a biplanar
      set-up.
AB  - Model-based Roentgen Stereophotogrammetric Analysis (RSA) was recently developed
      for the measurement of prosthesis micromotion. Its main advantage is that markers
      do not need to be attached to the implants as traditional marker-based RSA
      requires. Model-based RSA has only been tested in uniplanar radiographic set-ups.
      A biplanar set-up would theoretically facilitate the pose estimation algorithm,
      since radiographic projections would show more different shape features of the
      implants than in uniplanar images. We tested the precision of model-based RSA and
      compared it with that of the traditional marker-based method in a biplanar set
      up. Micromotions of both tibial and femoral components were measured with both
      the techniques from double examinations of patients participating in a clinical
      study. The results showed that in the biplanar set-up model-based RSA presents a
      homogeneous distribution of precision for all the translation directions, but an
      inhomogeneous error for rotations, especially internal-external rotation
      presented higher errors than rotations about the transverse and sagittal axes.
      Model-based RSA was less precise than the marker-based method, although the
      differences were not significant for the translations and rotations of the tibial
      component, with the exception of the internal-external rotations. For both
      prosthesis components the precisions of model-based RSA were below 0.2 mm for all
      the translations, and below 0.3 degrees for rotations about transverse and
      sagittal axes. These values are still acceptable for clinical studies aimed at
      evaluating total knee prosthesis micromotion. In a biplanar set-up model-based
      RSA is a valid alternative to traditional marker-based RSA where marking of the
      prosthesis is an enormous disadvantage.

PMID- 18635361
TI  - Pain and affective distress before and after ACL surgery: a comparison of amateur
      and professional male soccer players in the early postoperative period.
AB  - Pain thresholds and levels of distress before and in the early postoperative
      period after anterior cruciate ligament surgery were measured in professional and
      amateur male soccer players and compared. Between June 2005 and March 2007, 30
      soccer players (10 amateur, 20 professional) with acute or chronic tears of the
      anterior cruciate ligament who were scheduled for a bone-tendon-bone ACL
      reconstruction procedure were enrolled in the study. Measures of pain intensity,
      depression and anxiety were assessed 1 day pre-operation and 1 week and 3 weeks
      post-operation (T1 T2 and T3). Pain was assessed using a visual analog scale
      (VAS), depression with the Beck Depression Inventory (BDI), and anxiety with both
      the state and trait forms of the State-Trait Anxiety Inventory (STAI). Scores on
      the VAS, BDI, and STAI in both groups were analyzed. The mean VAS scores at T1
      and T2 in professional players were not significantly higher than those in
      amateur players (P>0.05). Professionals had significantly higher BDI scores at T1
      and T2 (P<0.05), but this difference was not significant at T3 (P=0.12). High
      depression scores did not correlate with high pain scores. Pain scores between
      professional and amateur soccer players with ACL injuries were not significantly
      different pre-op or in the early post-op period. Depression was more common in
      professionals before and after their ACL surgery, but anxiety levels were not
      significantly different between the two groups.

PMID- 18635362
TI  - Synthesis of scyllo-inositol derivatives and their effects on amyloid beta
      peptide aggregation.
AB  - scyllo-Inositol has shown promise as a potential therapeutic for Alzheimer's
      disease, by directly interacting with the amyloid beta (Abeta) peptide to inhibit
      Abeta42 fiber formation. To explore the molecular details of the inositol-Abeta42
      interaction, a series of scyllo-inositol derivatives have been synthesized which
      contain deoxy, fluoro, chloro, and methoxy substitutions. The effects of these
      compounds on the aggregation cascade of Abeta42 have been investigated using
      electron microscopy (EM). EM analyses revealed that the 1-deoxy-1-fluoro- and 1,4
      dimethyl-scyllo-inositols significantly inhibit the formation of Abeta42 fibers.
      The other derivatives showed some alterations in the morphology of the Abeta42
      fibers produced. These findings indicate the importance of all of the hydroxyl
      groups of scyllo-inositol for complete inhibition of Abeta aggregation.

PMID- 18635363
TI  - Synthesis and antiviral evaluation of some new pyrazole and fused
      pyrazolopyrimidine derivatives.
AB  - Some novel substituted pyrazole and pyrazolo[3,4-d]pyrimidine derivatives 2, 4,
      8, and 9 were synthesized. Also, some acyclic S-nucleosides of pyrazolo[3,4
      d]pyrimidine derivatives 10-13 were prepared via reaction of pyrazolo[3,4
      d]pyrimidine-4(3H)-thione derivative 9 with some acyclic sugars. Moreover, the N
      nucleoside derivative 14 was prepared via reaction of compound 8 with glucosamine
      hydrochloride. The antiviral evaluation of some selected new products showed that
      they have promising antiviral activity against hepatitis-A virus (HAV) and herpes
      simplex virus type-1 (HSV-1).

PMID- 18635364
TI  - TEM and HRTEM study of influence of thermal cycles with stress on dynamic
      recrystallization in Ti46Al8Nb1B during creep.
AB  - Short-term tension creep and thermal cycles under compressive stress were
      performed on Ti46Al8Nb1B in order to explore the dynamic recrystallization (DRX)
      grains formed during the creep and the impact of thermal cycles under stress to
      the DRX. After 1600 times' thermal cycles from 300 degrees C to 800 degrees C
      under 300 MPa compressive stress, high density of ledges and thick ledges are
      found in the interfaces. Two kinds of moire fringes, instead of 9R structure, can
      be found in the thick ledges. Ti46Al8Nb1B sample and another sample which was
      treated by thermal cycles with stress were crept under 300 MPa compressive stress
      at 800 degrees C. DRX grains are found in the interfaces in those samples. Those
      grains, formed at the ledges, have an orientation relationship of
      [101](gamma)//[011](gammaR), (1 1 1)(gamma)//(1 11 )(gammaR) with the matrix of
      gamma phases. Thermal cycles with stress could lead to more DRX grains during
      creep.

PMID- 18635365
TI  - Production of 93mMo through natY(7Li, 3n) reaction and subsequent studies on
      separation and extraction behaviour of no-carrier-added 93mMo from an yttrium
      target.
AB  - The present work reports heavy-ion-assisted production of (93m)Mo from a natural
      yttrium target using the (89)Y((7)Li, 3n)(93m)Mo reaction. Three different
      methodologies based on liquid-liquid extraction (LLX), aqueous biphasic
      extraction and precipitation, have been developed for separation and extraction
      of no-carrier-added (nca) (93m)Mo (T(1/2)=6.85h) radionuclide from bulk yttrium
      target. Complete separation of nca Mo from the target Y has been achieved by
      employing LLX technique with 0.1M trioctylamine (TOA) dissolved in cyclohexane
      and 8M HCl. Quantitative separation of (93m)Mo from the yttrium target is also
      possible by precipitating bulk yttrium with 1M oxalic acid. However, for this
      particular case, studies have shown that the aqueous biphasic extraction is not
      the method of choice for separation of nca Mo. Nevertheless, the extraction
      pattern is important in the context of simulation experiments for studying the
      behaviour of (106)Sg. Similarity or dissimilarity between the extraction patterns
      in various analytical systems will be helpful to decisively place Sg in the right
      position in the periodic table.

PMID- 18635366
TI  - Distal aortic arch aneurysm with a retroesophageal right subclavian artery
      (arteria lusoria).

PMID- 18635367
TI  - Could we still improve early and interim outcome after prosthetic systemic
      pulmonary shunt? A risk factors analysis.
AB  - OBJECTIVE: To identify factors associated with in-hospital and interim mortality
      in children with a systemic-to-pulmonary shunt (SPS). METHODS: Between January
      1988 and April 2005, 226 children with a median age of 17 days, and weight of 3.4
      kg, underwent an isolated SPS for pulmonary atresia (PA)-VSD/ tetralogy (n=124,
      54.9%), functional single ventricle PA (n=35, 5.5%), PA-intact septum (IS, n=31,
      13.7%), transposition of the great arteries VSD-PA (n=30, 13.3%), and double
      outlet right ventricle-PA (n=6, 2.6%). Surgery was performed through sternotomy
      (group S, n=46) or thoracotomy (group T, n=180). The origin of the SPS was either
      the innominate artery (n=38) or ascending aorta (n=8) in group S, and the
      subclavian artery (n=180) in group T. RESULTS: In-hospital mortality was 5.7%.
      Univariate and logistic regression analysis revealed younger age (p=0.01), lower
      body weight (p<0.04), a diagnosis of PA-IS with severe right ventricle hypoplasia
      (p=0.005), preoperative intubation (p=0.03), increased length of intubation
      (p<0.0001), longer ICU stay (p<0.0001), and group S (p=0.03) as risk factors for
      in-hospital death. Group S had a longer median ventilation time (112 vs 30 h,
      p<0.0001) despite the similar median age, weight, mean indexed shunt size (1.19
      vs 1.15 mm/kg, p=0.2), and the number of patients with antegrade pulmonary flow.
      Interim mortality was 7% (n=15), and younger age (p=0.03), and group T (p=0.03)
      were independent risk factors for death prior to second-stage surgery. Absence of
      antiplatelet agents or anticoagulants was not a risk factor for interim
      mortality. CONCLUSIONS: In-hospital mortality and longer ventilation time after
      SPS by sternotomy may be related to pulmonary over circulation due to shunt
      insertion origin and/or size, and pathologic features. Early and interim outcomes
      can be improved by using a smaller shunt or changing the SPS insertion origin
      when using a sternotomy approach.

PMID- 18635368
TI  - Reply to Van Schil and Stamatis Remediastinoscopy: a dangerous tool?

PMID- 18635370
TI  - Endovascular repair of the thoracic aorta in octogenarians.
AB  - BACKGROUND: To evaluate the feasibility and safety of thoracic endografting in
      the octogenarian population. METHODS: Between February 2000 and August 2005, 249
      patients with a mean age of 69+/-12.3 years (range 23-91) underwent thoracic
      endografting. Forty-four patients (27 males and 17 females) were octogenarians
      with a mean age of 84+/-2.7 years. Indications for intervention included:
      atherosclerotic aneurysms (26/44, 59%), acute and chronic dissections (9/44,
      20.5%), penetrating aortic ulcers (6/44, 14%) and contained rupture (3/44, 7%).
      RESULTS: Endovascular repair was achieved in all octogenarian patients (44/44,
      100%). Mean length of stay was 4.7+/-3.6 days. Two cardiac-related deaths and 1
      retrograde dissection death occurred (3/44, 7%). Complications included
      hemiparesis (n=2) with full recovery at discharge, groin hematoma (n=1),
      pneumonia (n=2) and stroke (n=1) [6/44, 11%]. Endoleaks were diagnosed in 3
      patients [3/44, 7%] (2 type I, 1 type II) at 30-day follow-up. Two patients
      developed an endoleak beyond 30 days [2/44, 5%] (1 type I, 1 type II). Two re
      interventions were necessary at 30 days (1 type I, 1 type II). Mean follow-up was
      22 months and there were no device migrations or aortic ruptures. No statistical
      differences in overall mortality were noted between octogenarians and non
      octogenarians at 30 days (7% vs 6%, p=NS), 12 months (18% vs 13%, p=NS) and 24
      months (27% vs 15%, p=NS). However, at 5 years post-procedure, octogenarians had
      a significantly higher overall mortality than non-octogenarians (32% vs 17%,
      p=0.038). CONCLUSIONS: Advanced age is not a contraindication to thoracic
      endografting with favorable short and mid-term outcomes compared to non
      octogenarians.

PMID- 18635371
TI  - Routine use of self-expanding venous cannulas for cardiopulmonary bypass:
      benefits and pitfalls in 100 consecutive cases.
AB  - OBJECTIVE: Assess the performance of self-expanding venous cannulas for routine
      use in open-heart surgery. METHODS: Prospective study in 100 unselected
      consecutive patients undergoing open-heart surgery with either remote or central
      smart venous cannulation. RESULTS: The study focuses on the 76 consecutive adult
      patients (mean age 59.2+/-17.3 years; 60 males, 16 females) undergoing surgical
      procedures with total cardiopulmonary bypass for either valve procedures (42/76
      patients=55.3%), ascending aorta and arch repair (20/76 patients=26.3%), coronary
      artery revascularization (13/76 patients=17.1%) or other procedures (11/76
      patients=14.5%) with 14/76 patients (18.4%) undergoing redo surgery and 6/76
      patients (7.9%) undergoing small access surgery. The mean pump flow achieved by
      gravity drainage alone accounted for 5.0+/-0.6l/min (=114% of target) in the
      entire study population (n=76) as compared to the calculated, theoretical pump
      flow of 4.4+/-0.5l/min (p<0.0001). For the femoral cannulation sub-group (n=35)
      pump flow achieved by gravity drainage alone accounted for 4.9+/-0.6l/min (=114%
      of target) as compared to the calculated theoretical pump flow of 4.3+/-0.4l/min
      (p<0.0001). The corresponding numbers for trans-subclavian cannulation (n=7) are
      5.2+/-0.5l/min (111%) for the pump flow achieved by gravity drainage as compared
      to the theoretical target flow of 4.7+/-0.4l/min. For the central cannulation sub
      group (n=34) mean flow achieved by gravity drainage with a self-expanding venous
      cannula accounted for 5.1+/-0.7l/min (=116% of target) as compared to the
      calculated theoretical flow of 4.4+/-0.6l/min (p<0.0001). CONCLUSION: Full or
      more than target flow was achieved in 97% of the patients studied undergoing CPB
      with self-expanding venous cannulas and gravity drainage. Remote venous
      cannulation with self-expanding cannulas provides similar flows as central
      cannulation. Augmentation of venous return is no longer necessary.

PMID- 18635372
TI  - Transition to intensive care nursing: establishing a starting point.
AB  - INTRODUCTION: There is a shortage of intensive care (IC) nurses. A supported
      transition to IC nursing has been identified as a key strategy for recruitment
      and retention. In 2004 a discussion document relating to transition of IC nurses
      was presented to the New South Wales (NSW) Chief Nursing Officer (CNO). A
      workshop was held with key stakeholders and a Steering Group was established to
      develop a state-wide transition to IC nursing program. AIMS: To survey
      orientation programs and educational resources and develop definitions, goals,
      learning objectives and clinical competencies relating to transition to IC
      nursing practice. METHODS: A questionnaire and a draft document of definitions,
      target group, goals, learning objectives and clinical competencies for IC
      transition was distributed to 43 NSW IC units (ICUs). An iterative process of
      anonymous feedback and modification was undertaken to establish agreement on
      content. RESULTS: Responses were received from 29 units (return rate of 67%). The
      survey of educational resources indicated ICUs had access to educational support
      and there was evidence of a lack of a common standard or definition for
      "orientation" or "transition". The definitions, target group, goals and
      competency statements from the draft document were accepted with minor editorial
      change. Seventeen learning objectives or psychomotor skills were modified and an
      additional 19 were added to the draft as a result of the process. CONCLUSION:
      This work has established valid definitions, goals, learning objectives and
      clinical competencies that describe transition to intensive care nursing.

PMID- 18635373
TI  - A regional citrate anticoagulation protocol for pre-dilutional CVVHDf: the
      'Modified Alabama Protocol'.
AB  - BACKGROUND: The use of citrate to anticoagulate the Continuous Renal Replacement
      Therapy (CRRT) circuit has not been widely adopted in Australia as an alternative
      to heparin due to treatment complexity and risks of metabolic complications and
      availability of suitable solutions. However, interest persists in citrate
      anticoagulation as a viable alternative when heparin is either contraindicated or
      has failed to provide an adequate circuit lifespan due to dialyser clotting. AIM:
      This paper will describe a regional citrate anticoagulation protocol based on the
      'Alabama Protocol' (AP) for pre-dilutional continuous veno-venous
      haemodiafiltration (CVVHDf) adapted to meet local requirements of an Australian
      tertiary medical-surgical intensive care unit. DISCUSSION: The 'Modified Alabama
      Protocol' (MAP) uses base solutions which are now commercially available in
      Australia to produce a 0.5% citrate concentrate as the replacement fluid and a
      bicarbonate based, calcium-free solution as the dialysate. A number of additives
      are required to be added to the base solutions in order to match the requirements
      of the protocol. The anticoagulatory effects of citrate are monitored by
      reviewing simultaneous blood samples taken from the patient's arterial line and
      the post-dialyser sample port of the CRRT circuit. Post-dialyser and systemic
      ionised calcium levels in addition to the patient's base excess are easily
      obtainable by processing the blood samples through a blood gas analyser on site
      in the intensive care unit. Acid-base and electrolyte disturbances are controlled
      by adjusting the flow rate of replacement fluid and dialysate. As the protocol
      provides consistent directions on how to achieve desired biochemical values and
      when medical intervention is required, the approach offers an ideal opportunity
      for trained nursing staff to follow such a protocol at the bedside. CONCLUSION:
      This paper describes a practical protocol for the delivery of regional citrate
      anticoagulation for pre-dilutional CVVHDf. The protocol maintains the flexibility
      in dialysis/haemofiltration dose prescription and advises on the requirement for
      monitoring and necessary adjustments to prevent the development of metabolic
      disturbances. This may assist regional citrate to achieve wider acceptance as an
      alternative anticoagulation strategy for critically ill patients.

PMID- 18635374
TI  - What factors influence suboptimal ward care in the acutely ill ward patient?
AB  - As technological developments continue to offer patients more health care choices
      patient acuity increases. Patients that traditionally would have been cared for
      in a critical care environment are increasingly located on general wards. This
      change impacts on the acute care sector in a number of ways. Patients who are
      inpatients have more complex problems and a greater number of co-morbidities and
      are therefore more likely to suffer physiological deterioration. Procedures
      requiring inpatient stays are often more complex and associated with higher rates
      of mortality and morbidity. As patient acuity has increased research has
      highlighted that the care of the acutely ill ward patient is suboptimal.
      Suboptimal care implies a lack of knowledge regarding the significance of
      clinical findings relating to dysfunction of airway, breathing and circulation.
      This paper analyses the literature on the factors that contribute to suboptimal
      ward care of the acutely ill patient. It uses the categories proposed by
      McQuillan et al. (1998) in relation to suboptimal ward care in an attempt to
      develop a conceptual analysis of the factors that influence suboptimal ward care
      and acutely ill ward patients. Thus it aims to develop and enhance practitioners'
      knowledge and understanding of this topic and therefore improve patient care
      outcomes.

PMID- 18635375
TI  - A strategy for direct identification of protein S-nitrosylation sites by
      quadrupole time-of-flight mass spectrometry.
AB  - S-nitrosylation of proteins serves an important role in regulating diverse
      cellular processes including signal transduction, DNA repair, and
      neurotransmission. Identification of S-nitrosylation sites is crucial for
      understanding the significance of this post-translational modification (PTM) in
      modulating the function of a protein. However, it is challenging to identify S
      nitrosylation sites directly by mass spectrometric (MS) methods due to the labile
      nature of the S-NO bond. Here we describe a strategy for direct identification of
      protein S-nitrosylation sites in an electrospray ionization (ESI) quadrupole time
      of-flight (QTOF) mass spectrometer without prior chemical derivatization of S
      nitrosylated peptides. Both sample buffer composition and MS hardware parameters
      were carefully adjusted to ensure that S-nitrosylated peptide ions could be
      analyzed by the QTOF MS with optimal signal/noise ratios. It was crucial that the
      proteins were preserved in a sample solution containing 1 mM EDTA and 0.1 mM
      neocuproine at neutral pH. Proteins dissolved in this solution are amenable to in
      solution tryptic digestion, which is important for the analysis of biological
      samples. S-nitrosylated peptides were effectively analyzed by LC/MS/MS on QTOF
      MS, with an optimized cone voltage of 20 V and collision energy of 4 V. We have
      successfully applied this method to thioredoxin, a key antioxidant protein, and
      identified within it an S-nitrosylation site at Cys73.

PMID- 18635376
TI  - Computer simulation of the gap-tripole ion trap with linear injection, 3D ion
      accumulation, and versatile packet ejection.
AB  - The behavior of a completely new ion trap is shown with SIMION 7.0 simulations.
      The simulated trap, which was a mix of a linear and a 3D trap, was made by
      axially setting two ion guides with a gap between them. Each guide consisted of
      three rods with three symmetrically delayed radio frequency (rf) voltages
      (tripole). The "injected" ions were linearly contained by pulsed potentials on
      the entrance and exit plates. Then the three-dimensional (3D) rf field in the
      gap, which was created by the tripole special rod arrangement, could trap the
      ions when the translational energy was dampened by collisions with low-pressure
      nitrogen. Because the injected ions were trapped in the small gap, the trapping
      cycle could be repeated many times before ion ejection, so a high concentrated
      ion cloud could be obtained. This trapping and accumulation methodology is not
      possible in most conventional multipole linear traps with even number of poles.
      Compared with quadrupole linear trap at the same rf amplitude, tripole lost more
      ions due to strong charge repulsion in the ion cloud. However, tripole could
      catch up the ions at higher voltage. Radial and axial mass-independent ejection
      of the ions localized in the tripole gap was very simple, compared with
      conventional linear ion traps that need extra and complicated electrodes for
      effective axial ejection.

PMID- 18635377
TI  - Electrospray mass spectrometry and tandem mass spectrometry of bimetallic
      oxovanadium complexes.
AB  - A series of six bimetallic oxovanadium complexes (1-6; only one was purified)
      were investigated by electrospray quadrupole time-of-flight tandem mass
      spectrometry (ESI-QTOF-MS/MS) in negative-ion mode. Radical molecular anions
      [M]*(-) were observed in MS mode. Fragmentation patterns of [M]*(-) were
      proposed, and elemental compositions of most of the product ions were confirmed
      on the basis of the high-resolution ESI-CID-MS/MS spectra. A complicated series
      of low-abundance product ions similar to electron impact (EI) ionization spectra
      indicated the radical character of the precursor ions. Fragment ions at m/z 214,
      200, and 182 seem to be the characteristic ions of bimetallic oxovanadium
      complexes. These ions implied the presence of a V-O-V bridge bond, which might
      contribute to stabilization of the radical. To obtain more information for
      structural elucidation, three representative bimetallic oxovanadium complexes (1
      3) were analyzed further by MS in positive-ion mode. Positive-ion ESI-MS produced
      adduct ions of [M + H](+), [M + Na](+), and [M + K](+). The fragmentation
      patterns of [M + Na](+) were different than those of radical molecular anions
      [M]*(-). Relatively simple fragmentation occurred for [M + Na](+), possibly due
      to even-electron ion character. Negative-ion MS and MS/MS spectra of the
      hydrolysis product of Complex 1 supported these finding, in particular, the
      existence of a V-O-V bridge bond.

PMID- 18635378
TI  - Characterization of proton-bound acetate dimers in ion mobility spectrometry.
AB  - Ionized acetates were used as model compounds to describe gas-phase behavior of
      oxygen containing compounds with respect to their formation of dimers in ion
      mobility spectrometry (IMS). The ions were created using corona discharge at
      atmospheric pressure and separated in a drift tube before analysis of the ions by
      mass spectrometry. At the ambient operational temperature and pressure used in
      our instrument, all acetates studied formed dimers. Using a homolog series of n
      alkyl-acetates, we found that the collision cross section of a dimer was smaller
      than that of a monomer with the same reduced mass. Our experiments also showed
      that the reduced mobility of acetate dimers with different functional groups
      increased in the order n-alkyl <or= branched chain alkyl <or= cyclo alkyl <
      aromat. For mixed n-alkyl dimers we found that the reduced mobility of acetate
      dimers having the same number of carbons, for example a dimer of acetyl acetate
      and hexyl acetate has the same reduced mobility as a dimer composed of two butyl
      acetates. The fundamental behavior of acetate monomers and dimers described in
      this paper will assist in a better understanding of the influence of dimer
      formation in ion mobility spectrometry.

PMID- 18635380
TI  - Inverse zombies, anesthesia awareness, and the hard problem of unconsciousness.
AB  - Philosophical (p-) zombies are constructs that possess all of the behavioral
      features and responses of a sentient human being, yet are not conscious. P
      zombies are intimately linked to the hard problem of consciousness and have been
      invoked as arguments against physicalist approaches. But what if we were to
      invert the characteristics of p-zombies? Such an inverse (i-) zombie would
      possess all of the behavioral features and responses of an insensate being, yet
      would nonetheless be conscious. While p-zombies are logically possible but
      naturally improbable, an approximation of i-zombies actually exists: individuals
      experiencing what is referred to as "anesthesia awareness." Patients under
      general anesthesia may be intubated (preventing speech), paralyzed (preventing
      movement), and narcotized (minimizing response to nociceptive stimuli). Thus,
      they appear--and typically are--unconscious. In 1-2 cases/1000, however, patients
      may be aware of intraoperative events, sometimes without any objective indices.
      Furthermore, a much higher percentage of patients (22% in a recent study) may
      have the subjective experience of dreaming during general anesthesia. P-zombies
      confront us with the hard problem of consciousness--how do we explain the
      presence of qualia? I-zombies present a more practical problem--how do we detect
      the presence of qualia? The current investigation compares p-zombies to i-zombies
      and explores the "hard problem" of unconsciousness with a focus on anesthesia
      awareness.

PMID- 18635379
TI  - The Yin and Yang of HLA and KIR in human disease.
AB  - Killer cell immunoglobulin-like receptors (KIR) are expressed on natural killer
      (NK) cells and subsets of T cells. The KIR genes are polymorphic and the KIR gene
      complex is polygenic with varying numbers of inhibitory and activating receptors.
      HLA class I molecules serve as ligands for the KIR. Interactions of the
      independently segregating KIR and HLA loci are important for recognition of
      targets by NK cells as well as NK cell 'licensing'. Several disease association
      studies indicate a role for interactions between these loci in infectious
      diseases, autoimmune/inflammatory disorders, cancer and reproduction. Emerging
      functional data supports a mechanism based on a continuum of inhibition to
      activation through various compound KIR-HLA genotypes in diseases.

PMID- 18635381
TI  - Chronic pain and other sequelae in long-term breast cancer survivors: nationwide
      survey in Denmark.
AB  - OBJECTIVES: To investigate self-reported chronic pain and other sequelae in a
      nationally representative sample of long-term breast cancer survivors (BCS).
      DESIGN: Age-stratified random sample of 2,000 female BCS 5 years after primary
      surgery without recurrence drawn from the Danish Breast Cancer Cooperative Group
      register, which is representative regarding long-term BCS in Denmark. ASSESSMENT:
      Self-administered questionnaire including questions on sociodemography, chronic
      pain (6 months), health-related quality of life (HRQOL) and other sequelae
      related to breast cancer. Associations with treatment were investigated. Report
      of chronic pain was compared to normative data. RESULTS: The response rate was
      79%. Chronic pain prevalence of 42% was significantly higher in BCS compared to
      general population women (SRR: 1.32; 95% CI: 1.23-1.42). Sequelae related to
      breast cancer were paraesthesia 47%, chronic pain 29%, arm/shoulder swelling 25%,
      phantom sensations 19%, and allodynia 15%. Chronic pain related to breast cancer
      was significantly associated with poorer HRQOL and higher medicine consumption,
      and, in multiple logistic regression analysis, with age (<70 years), short
      education, being single (divorced, widowed, separated), radiotherapy, and time
      since operation <10 years. Radiotherapy and younger age were significantly
      associated with most sequelae. CONCLUSION: Chronic pain was more prevalent in BCS
      compared to the general population. Significant predictors for sequelae related
      to breast cancer were radiotherapy and younger age. Future research should
      therefore prioritize sequelae prevention.

PMID- 18635382
TI  - Rapid encoding of T(1) with spectral resolution in n-dimensional relaxation
      correlations.
AB  - Nuclear magnetic resonance (NMR) T(1) relaxation times have been encoded in the
      second dimension of two-dimensional relaxation correlation and exchange
      experiments using a rapid "double-shot"T(1) pulse sequence. This technique also
      retains chemical shift information (delta) for short T(2)( *) materials. In this
      way, a spectral dimension can be incorporated into a T(2)-T(1)-delta correlation
      without an increase in experimental time compared to the conventional, chemically
      insensitive T(1)-T(2) correlation. Here, the T(2)-T(1)-delta pulse sequence is
      used to unambiguously identify oil and water fractions in a permeable rock. A
      novel T(1)-T(1)-(delta) relaxation exchange measurement is also introduced and
      used to observe diffusive exchange of water in cellulose fibres.

PMID- 18635383
TI  - Austrian's triad complicated by suppurative pericarditis and cardiac tamponade: a
      case report and review of the literature.
AB  - Austrian's triad is a rare complication of disseminated Streptococcus pneumoniae
      infection consisting of pneumonia, meningitis, and endocarditis. We report what
      we believe to be the first case of Austrian's triad further complicated by
      purulent pericarditis and cardiac tamponade, and review the relevant literature.

PMID- 18635384
TI  - Clinical impact and risk factors for percutaneous gastrostomy wound infections
      due to resistant organisms.

PMID- 18635385
TI  - Streptococcus pyogenes subdural empyema not detected by computed tomography.
AB  - A previously healthy 5-year-old boy presented with a non-specific febrile illness
      and seizures. Streptococcus pyogenes was identified in his blood culture. The
      spinal fluid revealed minimal pleocytosis and an axial computed tomography (CT)
      scan of the head was normal. Ongoing symptoms prompted a magnetic resonance
      imaging, which revealed a subdural empyema. Our patient diverges from the few
      previously reported S. pyogenes intracranial infections in that there was neither
      an adjacent infection nor a bacterial meningitis. In addition, we discuss the few
      studies addressing the sensitivity of CT for the diagnosis of bacterial
      intracranial infections.

PMID- 18635386
TI  - Type 2 diabetes patient education in Reunion Island: perceptions and needs of
      professionals in advance of the initiation of a primary care management network.
AB  - AIM: This study focused on issues in the education of type 2 diabetes patients in
      primary care on Reunion Island which, in a medical context, is broadly similar to
      metropolitan France, but with a much greater prevalence of diabetes. The aim was
      to assess the perceptions, training, reported practices and needs of health care
      providers in the field of patient education in advance of the initiation of a
      health care management network for diabetic patients. METHODS: A total of 74
      physicians and 63 nurses completed a detailed questionnaire comprising 52 items
      divided into six parts: professional activity, initial and postgraduate training,
      educational practices, objectives of patient education, perceived barriers and
      prospects for optimization. RESULTS: Educational activities for patients are
      almost nonexistent. Information and explanations given during a face-to-face
      encounter with the physician or nurse that combine technical and caring
      approaches are the main reasons reported for patient education. The obstacles
      reported by professionals that need to be overcome are limited available time,
      patient passivity and inadequate staff training. Practitioners and nurses are
      poorly taught as regards patient education and self-management of chronic
      diseases. The suggested improvements include professional acknowledgement, more
      convenient and available tools and improved postgraduate training. CONCLUSION:
      Patient education in primary care is still mostly an illusion, with many gaps
      that hinder education for both patients and professionals. The training of health
      professionals needs to meet the challenge of chronic diseases by integrating
      aspects from the fields of education and the social sciences.

PMID- 18635387
TI  - Camptocormia and dropped head syndrome as a clinic picture of myotonic myopathy.
AB  - Dropped head syndrome is primarily based on weakness localized at neck extensors.
      It may result from motor neuron disease, myasthenia gravis, and chronic
      inflammatory demyelinating polyneuropathy and also from various neuromuscular
      diseases including inflammatory, dystrophic and metabolic myopathies.
      Camptocormia (CC) on the other hand is an unusual condition characterized by
      progressive weakness of the extensor vertebral muscles and results in involuntary
      trunk flexion. CC may emerge as a clinical feature of many different conditions
      such as several myopathies and Parkinson's disease. The association of dropped
      head syndrome with CC has been rarely published in the literature. However, this
      is the only case presenting with concomitant dropped head syndrome and CC as a
      clinical picture of myotonic dystrophy (MD). In this report we aimed to represent
      a female patient, who was diagnosed as having myotonic dystrophy, with concurrent
      dropped head syndrome and CC.

PMID- 18635388
TI  - Hazards, risks and safety of diagnostic ultrasound.
AB  - The safety of exposure to diagnostic ultrasound is evaluated using a structured
      approach to risk assessment, based on the acoustic output of present ultrasound
      scanners. Thermal hazard is described, the magnitude and probability of
      temperature rise is reviewed, and the severity of harm from any outcome is
      reviewed. Similar assessments are made separately for acoustic cavitation and gas
      body effects, which have previously been considered together. Finally, radiation
      pressure is considered in a similar manner. In each case, means to minimize the
      risk are suggested where appropriate. The highest risks are associated with the
      use of gas-bubble contrast agents. It is concluded that there is a medium risk
      associated with trans-cranial Doppler use, and that this use of ultrasound
      deserves more detailed safety review. The risks associated with the current
      practice of obstetric ultrasound are low. Whilst the severity of radiation
      pressure as a hazard is low, it is always present. Little is known about any
      associated cell responses and so the associated risk cannot be evaluated.

PMID- 18635389
TI  - Nutritional improvements in plants: time to bite on biofortified foods.
AB  - Modern breeding, molecular genetic and biotechnology studies frequently describe
      changes in plant metabolism to improve nutritional content; however, this is
      often where the process of assessing biofortification ends. Ideally, these
      modified plants need to be used in controlled animal and human feeding studies to
      assess nutritional impact. Such bioavailability studies are crucial if any claims
      are to be made regarding health benefits and might be an important component in
      public acceptance of biofortified foods.

PMID- 18635390
TI  - Glutamine prevents DMBA-induced squamous cell cancer.
AB  - The etiology of oral squamous cell carcinoma has been linked to environmental
      carcinogens, such as activated aromatic heterocyclic radicals and epoxides. Our
      previous work on implantable and 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      breast cancer showed that oral glutamine (GLN) inhibited tumor growth possibly
      through stimulation of host - and selective inhibition of tumor glutathione
      (GSH). This finding was associated with up-regulation of NK cell activity,
      decreased IGF-1 and TGF-beta in the circulation and downregulation of PI-3K/Akt
      antiapoptotic signaling in tumors. The present study was designed to investigate
      the effect of topically applied GLN on DMBA-induced hamster buccal pouch squamous
      cell carcinoma. Histopathological alterations in buccal pouches were studied by
      light microscopy. GLN and GSH levels in blood and buccal mucosa were determined
      using specific enzyme assays. The protein expression of bax, bcl-2 and PARP was
      determined by western blotting. H-ras and p53 genes were examined for presence of
      mutations using direct DNA sequencing. Fourteen weeks after DMBA application none
      of the GLN-supplemented animals developed tumors, while all of the control
      animals had well developed squamous cell carcinomas. The inhibition of DMBA
      carcinogenesis by GLN application was associated with increased arterial GLN and
      GSH, elevated buccal mucosa GSH as well as induction of bax and PARP, and
      inhibition of bcl-2. H-ras and p53 were wild type. The results from this study in
      combination with our previous data suggest that the chemopreventive effects of
      GLN are exerted by enhancing the antioxidant status of the body and activation of
      apoptosis.

PMID- 18635391
TI  - Absorption spectra in the vacuum ultraviolet region of small molecules in
      condensed phases.
AB  - With radiation from a synchrotron we measured the spectra of several small
      molecular species, in the solid phase at 10K, either pure--O2, NO, CO2, N2O, H2O
      and NH3--or, for NH3, also dispersed in Ar at molar ratio 1/250, from the onset
      of absorption in the ultraviolet region until the limits of transmission by
      crystalline LiF or solid Ar. In a quantitative treatment of spectral data, we
      fitted the total absorption profile divided by wavenumber to Gaussian curves of
      minimal number, and made tentative assignments of electronic transitions and
      vibrational structure by comparison with spectra of gaseous species. These
      results illuminate the nature of electronic spectra of samples in solid phases in
      the vacuum ultraviolet region.

PMID- 18635392
TI  - Performance evaluation of the ADVIA Centaur anti-HBe and HBeAg assays.
AB  - BACKGROUND: Detection of HBeAg and anti-HBe is valuable for the evaluation and
      therapeutic management of hepatitis B infection. OBJECTIVES: To determine the
      clinical performance of the newly CE-approved(a) HBeAg and anti-HBe assays on the
      fully automated, random access ADVIA Centaur immunoassay system. STUDY DESIGN:
      Patient samples collected at two sites were used to compare the ADVIA Centaur
      assays to Abbott AxSYM assays. Consensus of discordant results was reached using
      Roche Elecsys assays. Additionally, two well-characterized seroconversion panels
      were evaluated. RESULTS: The ADVIA Centaur HBeAg assay sensitivity was 100% and
      specificity was 99.5%. The ADVIA Centaur anti-HBe assay sensitivity was 100% and
      the resolved specificity was 98.2%. Fewer samples required retesting with the
      ADVIA Centaur assays than with the AxSYM. In two well-characterized
      seroconversion panels, the ADVIA Centaur anti-HBe assay detected anti-HBe 20-25
      days earlier than the AxSYM assay; the ADVIA Centaur and AxSYM HBeAg assays
      detected HBe reactivity on the same day. CONCLUSIONS: The ADVIA Centaur HBeAg and
      anti-HBe assays demonstrated good sensitivity and specificity, and thus are
      suitable for clinical use. Their novel algorithms require reduced retesting,
      suggesting these assays may be more cost effective.

PMID- 18635393
TI  - Evaluation of the new ARCHITECT anti-HCV screening test under routine laboratory
      conditions.
AB  - BACKGROUND: An improved test version of the Abbott ARCHITECT anti-hepatitis C
      virus (HCV) test became available at the end of 2005. STUDY DESIGN: We compared
      the new test version with the Ortho Vitros anti-HCV test by evaluating 2034 serum
      samples in parallel on both systems under routine laboratory conditions.
      Discordant samples were tested in the Inno-LIA HCV Score assay as well as in the
      RIBA HCV 3.0. RESULTS: Of the 2034 samples 140 (6.9%) yielded positive and 1856
      (91.2%) negative results in both assays. We observed discordant results in 38
      samples (1.9%). All discrepant samples showed a low S/CO ratio of 1.0-6.9 (mean
      2.8) in the Ortho assay and of 1.3-3.0 (mean 1.96) in the ARCHITECT assay. As
      expected, most of them could not be confirmed by immunoblot testing. Comparison
      of the results of the two immunoblots (Inno-LIA and RIBA) revealed a great
      variability in test results. CONCLUSIONS: This study represents the first
      comparative evaluation of the modified version of the Abbott ARCHITECT anti-HCV
      assay in comparison with the Ortho Vitros anti-HCV test. Under routine laboratory
      testing, we observed good overall concordance between the two assays and no
      evidence that one assay shows more false-reactive or negative results than the
      other.

PMID- 18635395
TI  - A new gland associated with the retrocerebral complex of the adult corn earworm,
      Helicoverpa zea.
AB  - We report the discovery of a single-celled putative new gland associated with the
      retrocerebral complex in the adults of Helicoverpa zea. The gland was not
      observed in Manduca sexta and few other species of moths. The pair of glands,
      each 50.6+/-5.5 microm in diameter, is located on either side of the recurrent
      nerve. Each gland is connected on one end through a fine nerve to the nervus
      corporis cardiaci-3 (NCC-3) and at the opposite end to the corpora allata through
      a thin fiber. The gland is composed of a giant cell with a large nucleus. The
      cytoplasm has an abundance of mitochondria in addition to dense bodies, electron
      lucent spheres, concentric whorls of rough endoplasmic reticulum and few
      vacuoles. At this stage we have no idea as to the function of this new gland.

PMID- 18635394
TI  - Frequency changes in a continuous tone: auditory cortical potentials.
AB  - OBJECTIVE: We examined auditory cortical potentials in normal hearing subjects to
      spectral changes in continuous low and high frequency pure tones. METHODS:
      Cortical potentials were recorded to increments of frequency from continuous 250
      or 4000Hz tones. The magnitude of change was random and varied from 0% to 50%
      above the base frequency. RESULTS: Potentials consisted of N100, P200 and a slow
      negative wave (SN). N100 amplitude, latency and dipole magnitude with frequency
      increments were significantly greater for low compared to high frequencies.
      Dipole amplitudes were greater in the right than left hemisphere for both base
      frequencies. The SN amplitude to frequency changes between 4% and 50% was not
      significantly related to the magnitude of spectral change. CONCLUSIONS:
      Modulation of N100 amplitude and latency elicited by spectral change is more
      pronounced with low compared to high frequencies. SIGNIFICANCE: These data
      provide electrophysiological evidence that central processing of spectral changes
      in the cortex differs for low and high frequencies. Some of these differences may
      be related to both temporal- and spectral-based coding at the auditory periphery.
      Central representation of frequency change may be related to the different
      temporal windows of integration across frequencies.

PMID- 18635396
TI  - An ontogenetic analysis of locustatachykinin-like expression in the central
      complex of the grasshopper Schistocerca gregaria.
AB  - We have investigated the ontogenetic basis of locustatachykinin-like expression
      in a group of cells located in the pars intercerebralis of the grasshopper
      midbrain. These cells project fibers to the protocerebral bridge and the central
      body via a characteristic set of fiber bundles called the w, x, y, z tracts.
      Lineage analyses associate the immunoreactive cells with one of four neuroblasts
      (termed W, X, Y, Z) in each protocerebral hemisphere of the early embryo.
      Locustatachykinin is a ubiquitous myotropic peptide among the insects and its
      expression in the pars intercerebralis begins at approximately 60-65% of
      embryogenesis. This coincides with the appearance of the columnar
      neuroarchitecture characteristic of the central body. The number of
      immunoreactive cells in a given lineage is initially small, increases
      significantly in later embryogenesis, and attains the adult situation (about 7%
      of a lineage) in the first larval instar after hatching. Although each neuroblast
      generates progeny displaying a spectrum of cell body sizes, there is a clear
      morphological gradient, which reflects birth order within the lineage.
      Locustatachykinin expressing cells are located stereotypically at or near the tip
      of their lineage, which an age profile reveals places them amongst the first born
      progeny of their respective neuroblasts. Although these neuroblasts begin to
      generate progeny at approximately 25-27% of embryogenesis, their daughter cells
      remain quiescent with respect to locustatachykinin expression for over 30% of
      embryogenesis.

PMID- 18635397
TI  - Higher order visual input to the mushroom bodies in the bee, Bombus impatiens.
AB  - To produce appropriate behaviors based on biologically relevant associations,
      sensory pathways conveying different modalities are integrated by higher-order
      central brain structures, such as insect mushroom bodies. To address this
      function of sensory integration, we characterized the structure and response of
      optic lobe (OL) neurons projecting to the calyces of the mushroom bodies in bees.
      Bees are well known for their visual learning and memory capabilities and their
      brains possess major direct visual input from the optic lobes to the mushroom
      bodies. To functionally characterize these visual inputs to the mushroom bodies,
      we recorded intracellularly from neurons in bumblebees (Apidae: Bombus impatiens)
      and a single neuron in a honeybee (Apidae: Apis mellifera) while presenting color
      and motion stimuli. All of the mushroom body input neurons were color sensitive
      while a subset was motion sensitive. Additionally, most of the mushroom body
      input neurons would respond to the first, but not to subsequent, presentations of
      repeated stimuli. In general, the medulla or lobula neurons projecting to the
      calyx signaled specific chromatic, temporal, and motion features of the visual
      world to the mushroom bodies, which included sensory information required for the
      biologically relevant associations bees form during foraging tasks.

PMID- 18635398
TI  - Pluripotent human stem cell lines: what we can learn about cancer initiation.
AB  - Although the cancer stem cell (CSC) hypothesis has become an attractive model to
      account for tumor recurrence, failure to define a cell of origin has created the
      need to explore alternative models for cancer initiation and maintenance. Recent
      studies have linked an embryonic stem cell (ESC)-like gene signature with poorly
      defined high-grade tumors. Here, we review advances in the ESC field with an
      emphasis on how human pluripotent stem cells (hPSCs) can be used to define early
      tumorigenic events, including potential miRNA and epigenetic targets, as well as
      proto-oncogene and tumor suppressor networks that might facilitate hierarchal
      transformation. These studies allow for investigation of cancer initiation in a
      manner that cannot be achieved using primary tumors, where only retrospective
      evaluation of CSC development is possible. By comparing transformed hPSCs with
      their normal counterparts, we hope to develop novel cell-specific therapies that
      selectively target CSCs.

PMID- 18635399
TI  - Epigenetic mechanisms in drug addiction.
AB  - Changes in gene expression in brain reward regions are thought to contribute to
      the pathogenesis and persistence of drug addiction. Recent studies have begun to
      focus on the molecular mechanisms by which drugs of abuse and related
      environmental stimuli, such as drug-associated cues or stress, converge on the
      genome to alter specific gene programs. Increasing evidence suggests that these
      stable gene expression changes in neurons are mediated in part by epigenetic
      mechanisms that alter chromatin structure on specific gene promoters. This review
      discusses recent findings from behavioral, molecular and bioinformatic approaches
      being used to understand the complex epigenetic regulation of gene expression by
      drugs of abuse. This novel mechanistic insight might open new avenues for
      improved treatments of drug addiction.

PMID- 18635400
TI  - Pre-hospital delay in patients with acute coronary syndrome: factors associated
      with patient decision time and home-to-hospital delay.
AB  - BACKGROUND: Pre-hospital delays in patients experiencing acute coronary syndromes
      (ACS) remain unacceptably long. AIMS: To examine simultaneously a wide range of
      clinical, sociodemographic and situational factors associated with total pre
      hospital delay and its two components. METHODS: Pre-hospital delay data were
      collected from 228 patients with ACS using patient's medical notes and semi
      structured interviews. Total pre-hospital delay (symptom onset to hospital
      admission) was divided into 2 components: decision time (symptom onset to call
      for medical help), and home-to-hospital delay (call for help to hospital
      admission). RESULTS: Shorter total pre-hospital delays and decision times were
      associated with ST segment myocardial infarction (STEMI), recognizing symptoms as
      cardiac in origin, being married, symptom onset outside the home and the presence
      of a bystander. Shorter home-to-hospital delays were more likely among younger
      patients, those experiencing an STEMI, and patients reporting a greater number of
      symptoms. Initial contact with emergency medical services was related to shorter
      total delays and decision times. CONCLUSIONS: Different factors were associated
      with shorter times in the 2 component phases. Greater understanding of the
      factors impacting on the component phases may help target interventions more
      effectively and reduce pre-hospital delays.

PMID- 18635401
TI  - Sex chromosome complement affects nociception and analgesia in newborn mice.
AB  - In animal studies of nociception, females are often more sensitive to painful
      stimuli, whereas males are often more sensitive to analgesia induced by mu
      agonists. Sex differences are found even at birth, and in adulthood are likely
      caused, at least in part, by differences in levels of gonadal hormones. In this
      report, we investigate nociception and analgesia in neonatal mice and assess the
      contribution of the direct action of sex chromosome genes in hotplate and tail
      withdrawal tests. We used the 4 core genotypes mouse model, in which gonadal sex
      is independent of the complement of sex chromosomes (XX vs XY). Mice were tested
      at baseline and then injected with mu-opioid agonist morphine (10 mg/kg) or with
      the kappa-opioid agonist U50,488H (U50, 12.5 mg/kg) with or without the N-methyl
      D-aspartate (NMDA) receptor antagonist MK-801 (0.1 mg/kg). On the day of birth,
      XX mice showed faster baseline latencies than XY in tail withdrawal, irrespective
      of their gonadal type. Gonadal males showed greater effects of morphine than
      gonadal females in the hotplate test, irrespective of their sex chromosome
      complement. U50 and morphine were effective analgesics in both tests, but MK-801
      did not block the U50 effect. The results suggest that sex chromosome complement
      and gonadal secretions both contribute to sex differences in nociception and
      analgesia by the day of birth. PERSPECTIVE: Sex differences in pain may stem not
      only from the action of gonadal hormones on pain circuits but from the sex
      specific action of X and Y genes. Identification of sex chromosome genes causing
      sex differences could contribute to better pain therapy in females and males.

PMID- 18635402
TI  - Have wing morphology or flight kinematics evolved for extreme high altitude
      migration in the bar-headed goose?
AB  - Bar-headed geese (Anser indicus) migrate over the Himalayan mountains, at
      altitudes up to 9000 m above sea level, where air density and oxygen availability
      are extremely low. This study determined whether alterations in wing morphology
      or wingbeat frequency during free flight have evolved in this species to
      facilitate extreme high altitude migration, by comparing it to several closely
      related goose species. Wingspan and wing loading scaled near isometrically with
      body mass across all species (with power scaling exponents of 0.22 and 0.47,
      respectively), and wingbeat frequency scaled negatively to mass (scaling exponent
      of -0.167). Bar-headed geese had the largest wingspan residual and smallest wing
      loading residual from these allometric relationships, suggesting that they are at
      the top end of the wing size distribution. These morphological characters of bar
      headed geese were not outside the normal variation exhibited by low altitude
      species, however, being within the prediction intervals of the regression. This
      was particularly true after the data were corrected for phylogeny using the
      independent contrasts method. Wingbeat frequencies of bar-headed geese during
      steady flight were the same as low altitude geese, both with and without
      correcting for phylogeny. Without adjusting other kinematic features (e.g., wing
      motion and generated wake structure) to supplement lift generation in low air
      densities, the metabolic costs of flight in bar-headed geese at high altitude
      could exceed the already high costs at sea level. The apparent lack of
      morphological and kinematic adaptation emphasizes the importance of physiological
      adaptations for enhancing oxygen transport and utilization in this species.

PMID- 18635404
TI  - An approach towards method development for untargeted urinary metabolite
      profiling in metabonomic research using UPLC/QToF MS.
AB  - The application of LC-MS for untargeted urinary metabolite profiling in
      metabonomic research has gained much interest in recent years. However, the
      effects of varying sample pre-treatments and LC conditions on generic metabolite
      profiling have not been studied. We aimed to evaluate the effects of varying
      experimental conditions on data acquisition in untargeted urinary metabolite
      profiling using UPLC/QToF MS. In-house QC sample clustering was used to monitor
      the performance of the analytical platform. In terms of sample pre-treatment,
      results showed that untreated filtered urine yielded the highest number of
      features but dilution with methanol provided a more homogenous urinary metabolic
      profile with less variation in number of features and feature intensities. An
      increased cycle time with a lower flow rate (400 microl/min vs 600 microl/min)
      also resulted in a higher number of features with less variability. The step
      elution gradient yielded the highest number of features and the best
      chromatographic resolution among three different elution gradients tested. The
      maximum retention time and mass shift were only 0.03 min and 0.0015 Da
      respectively over 600 injections. The analytical platform also showed excellent
      robustness as evident by tight QC sample clustering. To conclude, we have
      investigated LC conditions by studying variability and repeatability of LC-MS
      data for untargeted urinary metabolite profiling.

PMID- 18635403
TI  - Coupling of airway ciliary activity and mucin secretion to mechanical stresses by
      purinergic signaling.
AB  - The mucociliary clearance system is comprised of three components, ion transport
      activities controlling the height of airway surface liquid (ASL), mucin
      secretion, and ciliary activity. These activities in humans are controlled
      principally by local agonists, extracellular nucleotides and nucleosides released
      from the epithelium. Importantly, mechanical stresses stimulate goblet cell mucin
      secretion, ciliary beating, and Cl- and fluid secretion through mechanically
      induced nucleotide release. Emerging evidence also implicates co-secretion of
      nucleotides and mucin from goblet cells as a source of extracellular agonist. At
      rest, ATP is released onto airway surfaces at approximately 370fmol/mincm2, but
      only approximately 3% of released ATP is recovered in ASL. Secreted UTP meets
      with a similar fate. A wide variety of hydrolytic and transphosphorylating ecto
      enzymes convert the triphosphate nucleotides into ADP, AMP, and adenosine, UDP,
      UMP, and uridine. Of these, ATP, adenosine, UTP, and UDP act as agonists at
      apical P2Y2 (ATP, UTP), P2Y6 (UDP), and A2B (adenosine) receptors on ciliated
      and/or goblet cells to regulate mucociliary clearance.

PMID- 18635405
TI  - Comparison of three GC/MS methodologies for the analysis of fatty acids in
      Sinorhizobium meliloti: development of a micro-scale, one-vial method.
AB  - Three protocols for fatty acid analysis in Sinorhizobium meliloti were improved
      by the addition of a number of standards/controls and a silylation step which
      allowed the determination of recoveries, extents of conversion of lipids to fatty
      acid methyl esters (FAMEs) and extents of side reactions. Basic hydrolysis
      followed by acid-catalyzed methylation and transmethylation with sodium
      methoxide, were the best for the analysis of 3-hydroxy- and cyclopropane fatty
      acids, respectively. A micro-scale, one-vial method that employed sodium
      methoxide/methanol was equally efficient and on a 1000-fold smaller scale than
      standard methods. Because this method avoids aqueous extractions, 3
      hydroxybutanoic acid was detected as its trimethylsilyloxy methyl ester along
      with FAMEs.

PMID- 18635406
TI  - High reproducibility of two-dimensional liquid chromatography using pH-driven
      fractionation with a pressure-resistant electrode.
AB  - Automated two-dimensional liquid chromatography using the PF2D system from
      Beckman Coulter provides a fractionation platform well suited for differential
      proteomic studies. To date, the reliability and reproducibility of PF2D has not
      been accurately tested. Here, we used an optimized software and a pressure
      resistant pH electrode, allowing a precise and reproducible control of the pH
      limits for each fraction during PF2D. We tested the reliability of this improved
      system by performing several rounds of fractionation using the same protein
      extract. Three UV maps were generated, leading to 54 chromatograms and more than
      3000 protein peaks. Using semi-automated software for peak-to-peak comparison
      between 2D-LC chromatograms, we demonstrate that the peak concordance is very
      high. The rates of concordance were higher in the second dimension repeatability
      tests, indicating that the limiting factors for 2D-LC reproducibility rely on the
      pI fractionation and sample preparation steps. The reproducibility between maps
      was closely related to pH curves similarities, further stressing the need of
      careful pH adjustment and precise electrode calibration.

PMID- 18635407
TI  - Isolation of a cytotoxic glycoprotein from the Scyphozoa Cyanea lamarckii by
      lectin-affinity chromatography and characterization of molecule interactions by
      surface plasmon resonance.
AB  - A biospecific lectin-affinity-based isolation process for a novel glycoprotein
      (ClGp1) from the venom of the pelagic jellyfish Cyanea lamarckii, is described
      and the isolated glycoprotein is chemically and biologically characterized
      according to size, molecular interaction and toxicity. The molecular mass of the
      isolated protein is 25.7 kDa as determined by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF). The carbohydrate content
      was calculated after enzymatic deglycosylation as 6.85 kDa. The glycoprotein is
      cytotoxic and could be isolated from cnidocysts of mesenteric and fishing
      tentacles. The binding behaviour of the glycoprotein to the lectins Concanavalin
      A (ConA) and Wheat Germ Agglutinin (WGA) was analyzed by surface plasmon
      resonance (SPR) and affinity constants in the range of K(D)=3.0 x 10(-7) M for
      ConA and 2.1 x 10(-6) M (pH 5.0) and 2.6 x 10(-6) M (pH 7.4) for WGA were
      obtained.

PMID- 18635408
TI  - Development and validation of a rapid and sensitive high-performance liquid
      chromatography-mass spectroscopy assay for determination of 17-(allylamino)-17
      demethoxygeldanamycin and 17-(amino)-17-demethoxygeldanamycin in human plasma.
AB  - A sensitive method was developed and validated for the measurement of 17
      (allylamino)-17-demethoxygeldanamycin (17AAG) and its active metabolite 17-amino
      17-demethoxygeldanamycin (17AG) in human plasma using 17
      (dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG) as an internal
      standard. After the addition of internal standard, 200 microL of plasma was
      extracted using ice cold acetonitrile followed by analysis on a Thermo Finnigan
      triple-quadruple mass spectrometer coupled to an Agilent 1100 HPLC system.
      Chromatography was carried out on a 50 mm x 2.1 mm Agilent Zorbax SB-phenyl 5
      microm column coupled to a 3mm Varian metaguard diphenyl pre-column using glacial
      acetic acid 0.1% and a gradient of acetonitrile and water at a flow rate of 500
      microL/min. Atmospheric pressure chemical ionization and detection of 17AAG, 17AG
      and 17DMAG were accomplished using selected reaction monitoring of m/z
      584.3>541.3, 544.2>501.2, and 615.3>572.3, respectively in negative ion mode.
      Retention times for 17AAG, 17AG, and 17DMAG were 4.1, 3.5, and 2.9 min,
      respectively, with a total run time of 7 min. The assay was linear over the range
      0.5-3000 ng/mL for 17AAG and 17AG. Replicate sample analysis indicated within-
      and between-run accuracy and precision within 15%. The recovery of 17AAG and 17AG
      from 200 microL of plasma containing 1, 25, 300, and 2500 ng/mL was 93% or
      greater. This high-performance liquid chromatographic tandem mass spectroscopy
      (HPLC/MS/MS) method is superior to previous methods. It is the first analytical
      method reported to date for the quantitation of both 17AAG and its metabolite
      17AG and can reliably quantitate concentrations of both compounds as low as 0.5
      ng/mL.

PMID- 18635409
TI  - Effect of the solute molecular structure on its enantioresolution on cellulose
      tris(3,5-dimethylphenylcarbamate).
AB  - The effects of the molecular structures for 13 structurally similar chiral
      solutes on their HPLC retention and enantioresolutions on a commercially
      important polysaccharide-based chiral stationary phase, cellulose tris(3,5
      dimethylphenylcarbamate) (CDMPC) are studied. Among these 13 solutes, only methyl
      ephedrine (MEph) shows significant enantioresolution. The retention factors of
      these chiral solutes vary significantly from 0.7 to 3.2 in n-hexane/2-propanol
      (90/10, v/v) at 298 K. The retention factors of some simpler non-chiral solutes
      having similar but fewer functional groups than their chiral counterparts are
      also studied under the same conditions and are compared to those of the chiral
      solutes. The H-bonding interactions between the functional groups of the solute
      and the C=O and NH functional groups of the polymer are probed with attenuated
      total reflection-infrared spectroscopy (ATR-IR) for the polymer, for binary
      sorbent-solute systems. The CDMPC IR amide band wavenumbers change significantly,
      indicating H-bonding interactions of the polymer C=O and NH groups with the
      solutes. The elution orders predicted for the enantiomers of these chiral solutes
      using molecular dynamics (MD) simulations of the polymer-solute binary systems
      are consistent with the HPLC results. The CDMPC cavity nano-structure and the
      potential interactions with chiral solutes are proposed based on HPLC data, IR
      data, and the simulations. The results are consistent with the three-point
      attachment model and support the hypothesis that significant enantioresolution
      requires at least three different synergistic interactions which can be a
      combination of steric hindrance, H-bonding, or pi-pi interactions.

PMID- 18635410
TI  - Myenteric neuronal loss in rats with experimental colitis: role of tissue
      transglutaminase-induced apoptosis.
AB  - BACKGROUND AND AIMS: Transglutaminases are tissue enzymes involved in different
      neuronal processes including maintenance and signalling. However, their up
      regulation elicited by a variety of noxae contributes to neurodegeneration. This
      study tested the hypothesis that experimental inflammation evoked
      transglutaminase up-regulation in myenteric neurons and that this event had an
      impact on neuronal survival. METHODS: Rats with or without trinitro-benzene
      sulphonic acid-induced colitis were used. One week after colitis induction,
      longitudinal muscle-myenteric plexus preparations were obtained from left colon
      to assess tissue-transglutaminase activity, protein and mRNA expression. Double
      labelling immunofluorescence using antibodies to neuron-specific enolase and
      transglutaminase was performed to identify myenteric neurons expressing
      transglutaminase. Additional sets of experiments evaluated the involvement of
      transglutaminase in the apoptotic process of cultured myenteric neurons. RESULTS:
      Compared to controls, rats with colitis showed several tranglutaminase/neuron
      specific enolase positive myenteric neurons. Western blot analysis and RT-PCR
      confirmed that in rats with colitis, the increased neuronal transglutaminase
      immunoreactivity was associated with an increased enzyme expression. Similarly,
      transglutaminase activity was significantly higher than in controls (1100+/-280 m
      U/g vs. 725+/-119 m U/g, p<0.05). In cultured myenteric neurons incubation with
      the specific transglutaminase inducer, retinoic acid, significantly increased
      neuronal apoptosis, whereas the presence of cystamine significantly reduced the
      number of apoptotic neurons. CONCLUSIONS: Experimental colitis evoked
      transglutaminase up-regulation and increased activity in myenteric neurons. This
      mechanism enhances neuronal susceptibility to apoptosis and could contribute to
      neuropathic changes during gut inflammation.

PMID- 18635411
TI  - Novel nano-particles as fillers for an experimental resin-based restorative
      material.
AB  - The purpose of this study is to compare the properties of two experimental
      materials, nano-material (Nano) and Microhybrid, and two trade products, Clearfil
      AP-X and Filtek Supreme XT. The flexural strength and modulus after 24h water
      storage and 5000 thermocycles, water sorption, solubility and X-ray opacity were
      determined according to ISO 4049. The volumetric behavior (DeltaV) after curing
      and after water storage was investigated with the Archimedes principle. ANOVA was
      calculated with p<0.05. Clearfil AP-X showed the highest flexural strength (154+/
      14 MPa) and flexural modulus (11,600+/-550 MPa) prior to and after thermocycling
      (117+/-14 MPa and 13,000+/-300 MPa). The flexural strength of all materials
      decreased after thermocycling, but the flexural modulus decreased only for Filtek
      Supreme XT. After thermocycling, there were no significant differences in
      flexural strength and modulus between Filtek Supreme XT, Microhybrid and Nano.
      Clearfil AP-X had the lowest water sorption (22+/-1.1 microg mm(-3)) and Nano had
      the highest water sorption (82+/-2.6 microg mm(-3)) and solubility (27+/-2.9
      microg mm(-3)) of all the materials. No significant differences occurred between
      the solubility of Clearfil AP-X, Filtek Supreme XT and Microhybrid. Microhybrid
      and Nano provided the highest X-ray opacity. Owing to the lower filler content,
      Nano showed higher shrinkage than the commercial materials. Nano had the highest
      expansion after water storage. After thermocycling, Nano performed as well as
      Filtek Supreme XT for flexural strength, even better for X-ray opacity but
      significantly worse for flexural modulus, water sorption and solubility. The
      performances of microhybrids were superior to those of the nano-materials.

PMID- 18635412
TI  - Natural origin scaffolds with in situ pore forming capability for bone tissue
      engineering applications.
AB  - This work describes the development of a biodegradable matrix, based on chitosan
      and starch, with the ability to form a porous structure in situ due to the attack
      by specific enzymes present in the human body (alpha-amylase and lysozyme).
      Scaffolds with three different compositions were developed: chitosan (C100) and
      chitosan/starch (CS80-20, CS60-40). Compressive test results showed that these
      materials exhibit very promising mechanical properties, namely a high modulus in
      both the dry and wet states. The compressive modulus in the dry state for C100
      was 580+/-33MPa, CS80-20 (402+/-62MPa) and CS60-40 (337+/-78MPa). Degradation
      studies were performed using alpha-amylase and/or lysozyme at concentrations
      similar to those found in human serum, at 37 degrees C for up to 90 days.
      Scanning electron micrographs showed that enzymatic degradation caused a porous
      structure to be formed, indicating the potential of this methodology to obtain in
      situ forming scaffolds. In order to evaluate the biocompatibility of the
      scaffolds, extracts and direct contact tests were performed. Results with the MTT
      test showed that the extracts of the materials were clearly non-toxic to L929
      fibroblast cells. Analysis of cell adhesion and morphology of seeded osteoblastic
      like cells in direct contact tests showed that at day 7 the number of cells on
      CS80-20 and CS60-40 was noticeably higher than that on C100, which suggests that
      starch containing materials may promote cell adhesion and proliferation. This
      combination of properties seems to be a very promising approach to obtain
      scaffolds with gradual in vivo pore forming capability for bone tissue
      engineering applications.

PMID- 18635413
TI  - Age influences the severity of Graves' ophthalmopathy.
AB  - This study compared the ocular manifestations of Graves' disease in different age
      groups and between genders. This was a retrospective study with a chart review of
      210 patients seen in the Kaohsiung Veterans General Hospital Ophthalmology
      Department from 1990 to 2006. Clinical manifestations were recorded, scored, and
      compared between different age groups and between genders. A total of 77 male and
      133 female patients were included. The mean age of the patients was 48.71 years
      (53.80 for male and 45.77 for female patients). The average ophthalmopathy score
      was 3.72 (4.51 for male and 3.26 for female patients). Age was positively
      correlated with ophthalmopathy score (p < 0.01). The male patients scored higher
      than the female patients, generally and in different age groups, but the
      difference did not reach a statistically significant level. One hundred and six
      patients underwent tests for thyroid-stimulating hormone receptor antibody
      (TRAb); 92 (86.80%) were positive, but the titers did not correlate with the
      severity of ophthalmopathy. In conclusion, the severity of Graves' ophthalmopathy
      is correlated with age (r = 0.286). Thus, older patients should be more closely
      followed up and more aggressively treated.

PMID- 18635414
TI  - TEL/AML1 fusion gene in childhood acute lymphoblastic leukemia in southern
      Taiwan.
AB  - Chromosomal abnormalities are found in 80-90% of childhood cases of acute
      lymphoblastic leukemia (ALL). Leukemia-specific chromosome aberrations not only
      have prognostic value, but also provide important clues for further investigation
      into leukogenesis, leukemic cell transformation, and proliferation. This study
      used reverse transcriptase-polymerase chain reaction techniques to detect
      transcripts of the leukemia-specific chromosome fusion gene, TEL/AML1, and to
      monitor the expression levels of the TEL-AML1 fusion transcript in ALL patients
      at sequential intervals during their treatment course. Twenty-five ALL patients
      were enrolled, including 20 who were newly diagnosed and five in relapse. The
      incidence of the TEL/AML1 fusion gene in this study was 32%. The clinical
      features of our eight TEL/AML1-positive ALL cases were similar to those in other
      studies. Blotting analysis of the levels of the TEL-AML1 fusion transcript was
      used to detect minimal residual disease. Reduced levels of TEL/AML1 expression
      were found in four of the six patients whose bone marrow or peripheral blood
      samples were obtained after treatment. Further investigation with a larger sample
      size is warranted.

PMID- 18635415
TI  - Exercise behavior in asthmatic children: effects of a summer camp fitness program
      in Taiwan.
AB  - This quasi experimental study aimed to examine the effects of a swimming-focused
      summer camp program on self-efficacy and exercise behavioral change in
      schoolchildren with asthma and their parental support. Forty-one asthmatic
      schoolchildren were recruited from a medical center and an asthma education
      association in southern Taiwan. The participants in the summer camp program were
      assigned to the experimental group; the control group comprised those who did not
      attend the summer camp program. Each child was paired with a parent. A total of
      16 child-parent pairs in the experimental group and 25 pairs in the control group
      were followed-up. This 1.5-day asthma summer camp program included 20 minutes of
      health education in physical activity, two sessions of swimming practice for the
      children, and a 2-hour conference with the parents. The outcome measures included
      an Exercise Self-Efficacy Questionnaire, Stages of Exercise Behavior Change
      Questionnaire, and a Parental Support for Exercise Questionnaire. Before
      implementing the program, the two groups differed significantly in terms of the
      severity of their asthma, as well as their pre-camp test scores of exercise self
      efficacy. Therefore, asthma severity levels and scores from the pre-camp exercise
      self-efficacy test were selected as two ANCOVA covariates. The adjusted means for
      stages of exercise behavior change on the 2-month post-camp test were
      significantly different between the two groups, F(1, 37) = 5.88 and p = 0.02.
      Compared with the control group, subjects who attended the summer camp reported
      more regular exercise behavior at the 2-month post-camp test. Thus, a summer camp
      program with swimming instruction can enhance the exercise behavior of
      schoolchildren with asthma. This program is highly recommended for managing
      schoolchildren with asthma.

PMID- 18635416
TI  - A longitudinal study of nausea and vomiting, fatigue and perceived stress in, and
      social support for, pregnant women through the three trimesters.
AB  - Nausea and vomiting (NV), fatigue, stress and social support during pregnancy
      have been well documented using cross-sectional research designs. However, few
      studies have addressed the patterns and relationships for these variables using a
      longitudinal research design. The purpose of this study was to examine the
      patterns of and relationships among NV, fatigue, perceived stress, and social
      support in pregnant women throughout the three trimesters. A prospective and
      longitudinal study was conducted from 2003 to 2005. Data were collected on four
      different measures: the Index of Nausea, Vomiting, and Retching (INVR), the
      Visual Analog Fatigue Scale (VAFS), the Perceived Stress Scale (PSS), and the
      Brief Social Support Questionnaire (BSSQ). A total of 91 pregnant women were
      recruited from prenatal clinics in southern Taiwan. One-way ANOVA indicated that
      INVR scores and fatigue were significantly different among the three trimesters,
      but that perceived stress and social support were not. Post hoc analyses, using
      least significant difference testing, indicated that the first trimester was
      associated with significantly higher levels of NV than were the second and third
      trimesters. The first and third trimesters had significantly higher fatigue
      levels than did the second trimester. Mixed models indicated that the differences
      among INVR scores among the three trimesters were independent of gravidity,
      planned pregnancy and age. The difference in fatigue between the first and second
      trimesters was independent of gravidity, planned pregnancy and age, but fatigue
      was positively associated with NV. Perceived stress was positively correlated
      with NV. However, when further examining the relationships among the key
      variables by adding fatigue, perceived stress was found to positively correlate
      with fatigue and not NV, and negatively correlated with social support. The
      findings of this study provide a more comprehensive understanding and evidence
      based data of the patterns of and relationships among the above four key
      variables for pregnant women throughout the three trimesters. This will help
      health care professionals to provide more effective and appropriate care
      strategies based on the different stages of pregnancy.

PMID- 18635417
TI  - Paratesticular metastasis of malignant melanoma: a case report.
AB  - We report a case of multimetastatic malignant melanoma that was diagnosed after
      histopathologic examination of the excised paratesticular mass. Our patient
      initially visited the neurosurgery clinic due to low back pain. After preliminary
      evaluation, he was referred to our clinic due to a right scrotal mass. We excised
      the paratesticular mass and testis. The histopathologic findings were consistent
      with malignant melanoma. He was referred to the oncology department for adjuvant
      treatment. The patient died during the third month of chemotherapy. Our case was
      unique because the malignant melanoma was widely metastatic and involved
      primarily paratesticular tissues without any invasion of the testis and
      epididymis.

PMID- 18635418
TI  - Postoperative disseminated intravascular coagulation in a patient with ureteral
      metastasis from gastric cancer.
AB  - A 66-year-old man, with a history of gastric signet ring cell carcinoma, was
      admitted due to intermittent dull pain in the left lower abdomen for 3 months.
      Left ureteral obstruction with suspicious tumor encasement and hydronephrosis was
      found on imaging studies. Endoscopic ureteral biopsy revealed infiltrating high
      grade urothelial carcinoma. As a result, he underwent left nephroureterectomy and
      bladder cuff excision. Unexpectedly, metastatic carcinoma of the left ureter from
      the stomach was the final diagnosis after comparison of the permanent sections of
      the two specimens. Unfortunately, acute disseminated intravascular coagulation
      developed and the patient died of disease complications 16 days after the
      operation, even with intensive care. The details of this rare condition are
      reported herein with a review of the medical literature.

PMID- 18635419
TI  - Pancreatic tail cancer with sole manifestation of left flank pain: a very rare
      presentation.
AB  - Pancreatic cancer is sometimes called a "silent disease" because it often causes
      no symptoms in the early stage. The symptoms can be quite vague and various
      depending on the location of cancer in the pancreas. The anatomic site
      distribution is 78% in the head of the pancreas, 11% in the body, and 11% in the
      tail. Pancreatic cancer is rarely detected in the early stage, and it is very
      uncommon to diagnose pancreatic tail cancer during an emergency department visit.
      The manifestation of pancreatic tail cancer as left flank pain is very rare and
      has seldom been identified in the literature. We present a case of pancreatic
      tail cancer with the sole manifestation of dull left flank pain. Having negative
      findings on an ultrasound study initially, this female patient was misdiagnosed
      as having possible acute gastritis, urolithiasis or muscle strain after she
      received gastroendoscopy and colonofiberscopy. Her symptoms persisted for several
      months and she visited our emergency department due to an acute exacerbation of a
      persistent dull pain in the left flank area. Radiographic evaluation with
      computed tomography was performed, and pancreatic tail tumor with multiple
      metastases was found unexpectedly. We review the literature and discuss this rare
      presentation of pancreatic tail cancer.

PMID- 18635420
TI  - Value of gallium-67 scanning in monitoring therapeutic effectiveness in a patient
      with relapsing polychondritis.
AB  - We present a 57-year-old man who had low-grade fever and painful, swollen and
      erythematous ears. Gallium-67 citrate scintigraphy (gallium scan) performed prior
      to the commencement of treatment showed increased gallium uptake in bilateral
      external ears, neck, mediastinum and bilateral pulmonary hili. The results of
      ultrasonography of both ears were compatible with the diagnosis of chondritis.
      The patient's clinical condition and laboratory data improved after a course of
      nonsteroidal anti-inflammatory drugs and steroids. Gallium scan performed after
      treatment showed a diminished uptake in the external ears, neck, and mediastinum.
      Gallium scintigraphy is a valuable tool for evaluating inflammatory activity and
      monitoring therapeutic response in patients with relapsing polychondritis.

PMID- 18635421
TI  - Bisindolylmaleimides in anti-cancer therapy - more than PKC inhibitors.
AB  - Bisindolylmaleimide derivatives were originally described as protein kinase C
      inhibitors. However, several studies have shown that bisindolylmaleimides target
      several other signaling molecules. The review presents bisindolylmaleimide
      mediated PKC-dependent and PKC-independent biological effects, such as reversal
      of MDR and modulation of Wnt signaling through GSK-3b and b-catenin. Importantly,
      the potent proapoptotic properties of bisindolylmaleimides are also described.
      Bis-IX appears as the most efficient activator of intrinsic apoptotic pathway and
      additionally, facilitates extrinsic apoptosis. Presented molecular mechanisms
      indicate that bisindolylmaleimides could be useful agents in anticancer therapy.
      They repress uncontrolled proliferation and restore the sensitivity to
      chemotherapy which allows eradication of cancer cells.

PMID- 18635422
TI  - Visfatin and apelin, new adipocytokines, and their relation to endothelial
      function in patients with chronic renal failure.
AB  - PURPOSE: Visfatin and apelin are novel adipocytokines that have recently
      generated much interest. The aim of the study was to assess visfatin and apelin
      in correlation with markers of endothelial cell injury and inflammation in 22
      patients with chronic kidney disease-CKD and 22 age- and sex-matched healthy
      volunteers. METHODS: We assessed visfatin, apelin, markers of coagulation: TAT
      (thrombin-antithrombin complexes), prothrombin fragments 1+2; fibrinolysis: tPA
      (tissue plasminogen activator), PAI-1 (plasminogen activator inhibitor), PAP
      (plasmin-antiplasmin complexes); endothelial function/injury: vWF (von Willebrand
      factor), thrombomodulin, ICAM (intracellular adhesion molecule), VCAM (vascular
      cell adhesion molecule), CD146, CD40L, CD44, E-selectin, inflammation: hsCRP.
      RESULTS: Triglycerides, hsCRP, creatinine, vWF, prothrombin fragments 1+2, TAT,
      thrombomodulin, ICAM, VCAM, CD146, CD44, CD40L, PAI-1, PAP, visfatin and E
      selectin were elevated in chronic kidney disease patients when compared with the
      control group. Visfatin correlated significantly in patients with chronic kidney
      disease, in univariate analysis, with CD40L (r=-0.27, p<0.05), apelin (r=0.27,
      p<0.05), ICAM (r=0.26, p<0.05), VCAM (r=0.31, p<0.05) and tended to correlate
      with CD146 (r=0.21, p=0.10). Apelin correlated significantly with E-selectin
      (r=0.31, p<0.05) and VCAM (r=0.31, p<0.05). In the healthy volunteers visfatin
      correlated significantly with ICAM (r=-0.37, p<0.05) and serum creatinine (0.38,
      p<0.05). CONCLUSIONS: Elevated visfatin in CKD patients may be due to renal
      failure and/or inflammation. Adipocytokines related to adhesion molecules might
      support the importance of inflammation/endothelial cell injury in the
      pathogenesis of atherosclerosis and its consequences in CKD.

PMID- 18635423
TI  - Quantitative morphology of the left subclavian artery in human fetuses.
AB  - PURPOSE: The present study was performed to compile normative data for dimensions
      of the left subclavian artery at varying gestational age. MATERIAL AND METHODS:
      Using anatomical dissection, digital image analysis (Leica Q Win Pro 16 system)
      and statistical analysis (ANOVA, regression analysis) a range of measurements
      (length, original external diameter, volume) for the left subclavian artery in
      128 spontaneously aborted human fetuses aged 15-34 weeks was examined. RESULTS:
      No significant gender differences were found (P>0.05). The length ranged from
      4.62 +/- 0.49 to 12.28 +/- 1.25 mm, according to the linear function y = -2.1482
      + 0.4302 x +/- 0.9972 (r = 0.93 P<0.001). The original external diameter
      increased from 0.68 +/- 0.16 to 2.89 +/- 0.29 mm, according to the linear model y
      = -1.2169 + 0.1233 x +/- 0.2389 (r = 0.95 P<0.001). The left subclavian artery-to
      aortic root diameter ratio increased from 0.337 +/- 0.064 to 0.423 +/- 0.103.
      Distance between the left common carotid and left subclavian arteries increased
      from 0.57 +/- 0.17 to 3.92 +/- 0.91 mm. Aortic arch diameter to distance between
      the left common carotid and left subclavian arteries decreased with advanced
      fetal age, from 2.82 +/- 0.51 to 1.56 +/- 0.27. The volume ranged from 1.77 +/-
      0.89 to 80.60 +/-; 22.18 mm3, in accordance with the quadratic function y = 76.0 
      8.956 x + 0.031 x2 +/- 10.945 (R2 = 0.85). CONCLUSIONS: The developmental
      dynamic of the length and diameter of the left subclavian artery follows a linear
      regression, whereas its volumetric dynamic follows a quadratic regression. The
      ratio of the aortic arch diameter to the distance between the left common carotid
      and left subclavian arteries has clinical application in the early recognition of
      aortic coarctation.

PMID- 18635424
TI  - Medicare showdown.

PMID- 18635425
TI  - Images in clinical medicine. Vitiligo and cutaneous melanoma.

PMID- 18635426
TI  - Relevance and rigor in premedical education.

PMID- 18635427
TI  - From all walks of life--nontraditional medical students and the future of
      medicine.

PMID- 18635428
TI  - Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
AB  - BACKGROUND: Trials comparing the effectiveness and safety of weight-loss diets
      are frequently limited by short follow-up times and high dropout rates. METHODS:
      In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean
      age, 52 years; mean body-mass index [the weight in kilograms divided by the
      square of the height in meters], 31; male sex, 86%) to one of three diets: low
      fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate,
      non-restricted-calorie. RESULTS: The rate of adherence to a study diet was 95.4%
      at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest
      amounts of dietary fiber and had the highest ratio of monounsaturated to
      saturated fat (P<0.05 for all comparisons among treatment groups). The low
      carbohydrate group consumed the smallest amount of carbohydrates and the largest
      amounts of fat, protein, and cholesterol and had the highest percentage of
      participants with detectable urinary ketones (P<0.05 for all comparisons among
      treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg
      for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group
      (P<0.001 for the interaction between diet group and time); among the 272
      participants who completed the intervention, the mean weight losses were 3.3 kg,
      4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total
      cholesterol to high-density lipoprotein cholesterol was 20% in the low
      carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects
      with diabetes, changes in fasting plasma glucose and insulin levels were more
      favorable among those assigned to the Mediterranean diet than among those
      assigned to the low-fat diet (P<0.001 for the interaction among diabetes and
      Mediterranean diet and time with respect to fasting glucose levels). CONCLUSIONS:
      Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat
      diets. The more favorable effects on lipids (with the low-carbohydrate diet) and
      on glycemic control (with the Mediterranean diet) suggest that personal
      preferences and metabolic considerations might inform individualized tailoring of
      dietary interventions. (ClinicalTrials.gov number, NCT00160108.)

PMID- 18635429
TI  - Rituximab and intravenous immune globulin for desensitization during renal
      transplantation.
AB  - BACKGROUND: Few options for transplantation currently exist for patients highly
      sensitized to HLA. This exploratory, open-label, phase 1-2, single-center study
      examined whether intravenous immune globulin plus rituximab could reduce anti-HLA
      antibody levels and improve transplantation rates. METHODS: Between September
      2005 and May 2007, a total of 20 highly sensitized patients (with a mean [+/-SD]
      T-cell panel-reactive antibody level, determined by use of the complement
      dependent cytotoxicity assay, of 77+/-19% or with donor-specific antibodies) were
      enrolled and received treatment with intravenous immune globulin and rituximab.
      We recorded rates of transplantation, panel-reactive antibody levels, cross
      matching results at the time of transplantation, survival of patients and grafts,
      acute rejection episodes, serum creatinine values, adverse events and serious
      adverse events, and immunologic factors. RESULTS: The mean panel-reactive
      antibody level was 44+/-30% after the second infusion of intravenous immune
      globulin (P<0.001 for the comparison with the pretreatment level). At study
      entry, the mean time on dialysis among recipients of a transplant from a deceased
      donor was 144+/-89 months (range, 60 to 324). However, the time to
      transplantation after desensitization was 5+/-6 months (range, 2 to 18). Sixteen
      of the 20 patients (80%) received a transplant. At 12 months, the mean serum
      creatinine level was 1.5+/-1.1 mg per deciliter (133+/-97 micromol per liter),
      and the mean survival rates of patients and grafts were 100% and 94%,
      respectively. There were no infusion-related adverse events or serious adverse
      events during the study. Long-term monitoring for infectious complications and
      neurologic problems revealed no unanticipated events. CONCLUSIONS: These findings
      suggest that the combination of intravenous immune globulin and rituximab may
      prove effective as a desensitization regimen for patients awaiting a transplant
      from either a living donor or a deceased donor. Larger and longer trials are
      needed to evaluate the clinical efficacy and safety of this approach.
      (ClinicalTrials.gov number, NCT00642655.)

PMID- 18635430
TI  - Effect of dissemination of evidence in reducing injuries from falls.
AB  - BACKGROUND: Falling is a common and morbid condition among elderly persons.
      Effective strategies to prevent falls have been identified but are underutilized.
      METHODS: Using a nonrandomized design, we compared rates of injuries from falls
      in a region of Connecticut where clinicians had been exposed to interventions to
      change clinical practice (intervention region) and in a region where clinicians
      had not been exposed to such interventions (usual-care region). The interventions
      encouraged primary care clinicians and staff members involved in home care,
      outpatient rehabilitation, and senior centers to adopt effective risk assessments
      and strategies for the prevention of falls (e.g., medication reduction and
      balance and gait training). The outcomes were rates of serious fall-related
      injuries (hip and other fractures, head injuries, and joint dislocations) and
      fall-related use of medical services per 1000 person-years among persons who were
      70 years of age or older. The interventions occurred from 2001 to 2004, and the
      evaluations took place from 2004 to 2006. RESULTS: Before the interventions, the
      adjusted rates of serious fall-related injuries (per 1000 person-years) were 31.2
      in the usual-care region and 31.9 in the intervention region. During the
      evaluation period, the adjusted rates were 31.4 and 28.6, respectively (adjusted
      rate ratio, 0.91; 95% Bayesian credibility interval, 0.88 to 0.94). Between the
      preintervention period and the evaluation period, the rate of fall-related use of
      medical services increased from 68.1 to 83.3 per 1000 person-years in the usual
      care region and from 70.7 to 74.2 in the intervention region (adjusted rate
      ratio, 0.89; 95% credibility interval, 0.86 to 0.92). The percentages of
      clinicians who received intervention visits ranged from 62% (131 of 212 primary
      care offices) to 100% (26 of 26 home care agencies). CONCLUSIONS: Dissemination
      of evidence about fall prevention, coupled with interventions to change clinical
      practice, may reduce fall-related injuries in elderly persons.

PMID- 18635431
TI  - Long-term medical and social consequences of preterm birth.
AB  - BACKGROUND: Advances in perinatal care have increased the number of premature
      babies who survive. There are concerns, however, about the ability of these
      children to cope with the demands of adulthood. METHODS: We linked compulsory
      national registries in Norway to identify children of different gestational-age
      categories who were born between 1967 and 1983 and to follow them through 2003 in
      order to document medical disabilities and outcomes reflecting social
      performance. RESULTS: The study included 903,402 infants who were born alive and
      without congenital anomalies (1822 born at 23 to 27 weeks of gestation, 2805 at
      28 to 30 weeks, 7424 at 31 to 33 weeks, 32,945 at 34 to 36 weeks, and 858,406 at
      37 weeks or later). The proportions of infants who survived and were followed to
      adult life were 17.8%, 57.3%, 85.7%, 94.6%, and 96.5%, respectively. Among the
      survivors, the prevalence of having cerebral palsy was 0.1% for those born at
      term versus 9.1% for those born at 23 to 27 weeks of gestation (relative risk for
      birth at 23 to 27 weeks of gestation, 78.9; 95% confidence interval [CI], 56.5 to
      110.0); the prevalence of having mental retardation, 0.4% versus 4.4% (relative
      risk, 10.3; 95% CI, 6.2 to 17.2); and the prevalence of receiving a disability
      pension, 1.7% versus 10.6% (relative risk, 7.5; 95% CI, 5.5 to 10.0). Among those
      who did not have medical disabilities, the gestational age at birth was
      associated with the education level attained, income, receipt of Social Security
      benefits, and the establishment of a family, but not with rates of unemployment
      or criminal activity. CONCLUSIONS: In this cohort of people in Norway who were
      born between 1967 and 1983, the risks of medical and social disabilities in
      adulthood increased with decreasing gestational age at birth.

PMID- 18635432
TI  - Exclusion of patients from pay-for-performance targets by English physicians.
AB  - BACKGROUND: In the English pay-for-performance program, physicians use a range of
      criteria to exclude individual patients from the quality calculations that
      determine their pay. This process, which is called exception reporting, is
      intended to safeguard patients against inappropriate treatment by physicians
      seeking to maximize their income. However, exception reporting may allow
      physicians to inappropriately exclude patients for whom targets have been missed
      (a practice known as gaming). METHODS: We analyzed data extracted automatically
      from clinical computing systems for 8105 family practices in England (96% of all
      practices), data from the U.K. Census, and data on practice characteristics from
      the U.K. Department of Health. We determined the rate of exception reporting for
      65 clinical activities and the association between this rate and the
      characteristics of patients and medical practices. RESULTS: From April 2005
      through March 2006, physicians excluded a median of 5.3% of patients
      (interquartile range, 4.0 to 6.9) from the quality calculations. Physicians were
      most likely to exclude patients from indicators that were related to providing
      treatments and achieving target levels of intermediate outcomes; they were least
      likely to exclude patients from indicators that were related to routine checks
      and measurements and to offers of treatment. The characteristics of patients and
      practices explained only 2.7% of the variance in exception reporting. We estimate
      that exception reporting accounted for approximately 1.5% of the cost of the pay
      for-performance program. CONCLUSIONS: Exception reporting brings substantial
      benefits to pay-for-performance programs, providing that the process is used
      appropriately. In England, rates of exception reporting have generally been low,
      with little evidence of widespread gaming.

PMID- 18635433
TI  - Acetylcysteine for acetaminophen poisoning.

PMID- 18635434
TI  - Images in clinical medicine. Sclerosing peritonitis.

PMID- 18635435
TI  - Case records of the Massachusetts General Hospital. Case 22-2008. A 52-year-old
      woman with fever and confusion.

PMID- 18635436
TI  - Reducing antibody levels in patients undergoing transplantation.

PMID- 18635437
TI  - The antiinflammatory IgG.

PMID- 18635438
TI  - Weekly paclitaxel in the adjuvant treatment of breast cancer.

PMID- 18635439
TI  - Carotid stenting versus endarterectomy.

PMID- 18635440
TI  - Artesunate for malaria.

PMID- 18635441
TI  - Case 12-2008: Apnea and seizures in a newborn infant.

PMID- 18635442
TI  - More on atypical fractures of the femoral diaphysis.

PMID- 18635443
TI  - Perinatal deaths in a family with autosomal dominant polycystic kidney disease
      and a PKD2 mutation.

PMID- 18635444
TI  - Resolution of non-small-cell lung cancer after withdrawal of anti-TNF therapy.

PMID- 18635446
TI  - Endotoxemia causes central downregulation of sympathetic vasomotor tone in
      healthy humans.
AB  - Experimental endotoxemia as a model of the initial septic response affects the
      autonomic nervous system with profound cardiovascular sequelae. Whether the
      postsynaptic sympathoneural activity to the muscle vascular bed is altered in the
      early septic phase remains to be determined. The present study aimed to elucidate
      the early effects of LPS on muscle sympathetic nerve activity (MSNA) and
      cardiovascular regulation in healthy humans. Young, healthy volunteers randomly
      received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n =
      7). Experimental baroreflex assessment (baseline measurements followed by
      infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and
      90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and
      blood levels of catecholamines, TNF-alpha and IL-6 were measured sequentially.
      Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels.
      In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min
      after injection [mean +/- SE: 12.1 +/- 2.9 vs. 27.5 +/- 3.3 burst/min (post- vs.
      pre-LPS); P < 0.005] but increased heart rate [78.4 +/- 3.1 vs. 60.6 +/- 2.0
      beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not
      altered, but baroreflex testing demonstrated a blunted MSNA response and
      uncoupling of heart rate modulation to blood pressure changes in the endotoxin
      group. We conclude that endotoxin challenge in healthy humans has rapid
      suppressive effects on postsynaptic sympathetic nerve activity to the muscle
      vascular bed and alters baroreflex function which may contribute to the untoward
      cardiovascular effects of sepsis.

PMID- 18635445
TI  - Effect of vaginal distention on elastic fiber synthesis and matrix degradation in
      the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse.
AB  - Matrix metalloprotease (MMP) activity is increased in the postpartum vagina of
      wild-type (WT) animals. This degradative activity is also accompanied by a burst
      in elastic fiber synthesis and assembly. The mechanisms that precipitate these
      changes are unclear. The goals of this study were to determine how vaginal
      distention (such as in parturition) affects elastic fiber homeostasis in the
      vaginal wall and the potential significance of these changes in the pathogenesis
      of pelvic organ prolapse. Vaginal distention with a balloon simulating
      parturition resulted in increased MMP-2 and MMP-9 activity in the vaginal wall of
      nonpregnant and pregnant animals. This was accompanied by visible fragmented and
      disrupted elastic fibers in the vaginal wall. In nonpregnant animals, the
      abundant amounts of tropoelastin and fibulin-5 in the vagina were not increased
      further by distention. In contrast, in pregnant animals, the suppressed levels of
      both proteins were increased 3-fold after vaginal distention. Distention
      performed in fibulin-5-deficient (Fbln5(-/-)) mice with defective elastic fiber
      synthesis and assembly induced accelerated pelvic organ prolapse, which never
      recovered. We conclude that, in pregnant mice, vaginal distention results in
      increased protease activity in the vaginal wall but also increased synthesis of
      proteins important for elastic fiber assembly. Distention may thereby contribute
      to the burst of elastic fiber synthesis in the postpartum vagina. The finding
      that distention results in accelerated pelvic organ prolapse in Fbln5(-/-)
      animals, but not in WT, indicates that elastic fiber synthesis is crucial for
      recovery of the vaginal wall from distention-induced increases in vaginal
      protease activity.

PMID- 18635447
TI  - Energetic responses to cold temperatures in rats lacking forebrain-caudal brain
      stem connections.
AB  - Hypothalamic neurons are regarded as essential for integrating thermal afferent
      information from skin and core and issuing commands to autonomic and behavioral
      effectors that maintain core temperature (T(c)) during cold exposure and for the
      control of energy expenditure more generally. Caudal brain stem neurons are
      necessary elements of the hypothalamic effector pathway and also are directly
      driven by skin and brain cooling. To assess whether caudal brain stem processing
      of thermal afferent signals is sufficient to drive endemic effectors for
      thermogenesis, heart rate (HR), T(c), and activity responses of chronic
      decerebrate (CD) and control rats adapted to 23 degrees C were compared during
      cold exposure (4, 8, or 12 degrees C) for 6 h. Other CDs and controls were
      exposed to 4 or 23 degrees C for 2 h, and tissues were processed for
      norepinephrine turnover (NETO), a neurochemical measure of sympathetic drive.
      Controls maintained T(c) for all temperatures. CDs maintained T(c) for the 8 and
      12 degrees C exposures, but T(c) declined 2 degrees C during the 4 degrees C
      exposure. Cold exposure elevated HR in CDs and controls alike. Tachycardia
      magnitude correlated with decreases in environmental temperature for controls,
      but not CDs. Cold increased NETO in brown adipose tissue, heart, and some white
      adipose tissue pads in CDs and controls compared with their respective room
      temperature controls. These data demonstrate that, in neural isolation from the
      hypothalamus, cold exposure drives caudal brain stem neuronal activity and
      engages local effectors that trigger sympathetic energetic and cardiac responses
      that are comparable in many, but not in all, respects to those seen in
      neurologically intact rats.

PMID- 18635448
TI  - Low temperature directly activates the initial glycerol antifreeze response in
      isolated rainbow smelt (Osmerus mordax) liver cells.
AB  - Rainbow smelt (Osmerus mordax) accumulate high levels of glycerol in winter that
      serve as an antifreeze. Liver glycogen is a source of glycerol during the early
      stages of glycerol accumulation, whereas dietary glucose and amino acids are
      essential to maintain rates of glycerol synthesis. We presently report rates of
      glycerol and glucose production by isolated hepatocytes. Cells from fish held at
      0.4 to -1.5 degrees C and incubated at 0.4 degrees C were metabolically quiescent
      with negligible rates of glycerol or glucose production. Hepatocytes isolated
      from fish maintained at 8 degrees C and incubated at 8 degrees C produced glucose
      but not glycerol. Glycerol production was activated in cells isolated from 8
      degrees C fish and incubated at 0.4 degrees C without substrate or when glucose,
      aspartate, or pyruvate was available in the medium. Incubation at 0.4 degrees C
      without substrate resulted in similar molar rates of glucose and glycerol
      production in concert with glycogen mobilization. Glycogenolysis and glycerol
      production were associated with increases in total in vitro activities of
      glycogen phosphorylase and glycerol-3-phosphate dehydrogenase. Maximal in vitro
      activities of hexokinase and glucokinase were not influenced by temperature, but
      high activities of a low-K(m) hexokinase may serve to redirect glycogen-derived
      glucose to glycolysis as opposed to releasing it from the cells. Rates of
      glycerol production were not enhanced in cells from fish held at 8 degrees C and
      incubated at 0.4 degrees C with adrenergic or glucocorticoid stimulation. As
      such, low temperature alone is sufficient to activate the glycerol production
      mechanism and results in a shift from glucose to a mix of glucose and glycerol
      production.

PMID- 18635449
TI  - Expression of Fos during sham sucrose intake in rats with central gustatory
      lesions.
AB  - For humans and rodents, ingesting sucrose is rewarding. This experiment tested
      the prediction that the neural activity produced by sapid sucrose reaches reward
      systems via projections from the pons through the limbic system. Gastric cannulas
      drained ingested fluid before absorption. For 10 days, the rats alternated an
      hour of this sham ingestion between sucrose and water. On the final test day,
      half of them sham drank water and the other half 0.6 M sucrose. Thirty minutes
      later, the rats were killed and their brains immunohistochemically stained for
      Fos. The groups consisted of controls and rats with excitotoxic lesions in the
      gustatory thalamus (TTA), the medial (gustatory) parabrachial nucleus (PBN), or
      the lateral (visceral afferent) parabrachial nucleus. In controls, compared with
      water, sham ingesting sucrose produced significantly more Fos-positive neurons in
      the nucleus of the solitary tract, PBN, TTA, and gustatory cortex (GC). In the
      ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the
      stria terminalis, central nucleus of amygdala, and the shell of nucleus
      accumbens. Thalamic lesions blocked the sucrose effect in GC but not in the
      ventral forebrain. After lateral PBN lesions, the Fos distributions produced by
      distilled H(2)O or sucrose intake did not differ from controls. Bilateral medial
      PBN damage, however, eliminated the sucrose-induced Fos increase not only in the
      TTA and GC but also in the ventral forebrain. Thus ventral forebrain areas
      associated with affective responses appear to be activated directly by PBN
      gustatory neurons rather than via the thalamocortical taste system.

PMID- 18635450
TI  - Linoleic acid increases chorda tympani nerve responses to and behavioral
      preferences for monosodium glutamate by male and female rats.
AB  - Previous studies suggest that the chorda tympani nerve (CT) is important in
      transmitting fat taste information to the central nervous system. However, the
      contribution of the CT in this process may depend upon the presence of other
      taste stimuli and/or differ in males and females. Accordingly, the present study
      investigated the role of the CT in free fatty acid taste processing by examining
      electrophysiological activity of the CT in response to the free fatty acid
      linoleic acid (LA), as well as by measuring behavioral responses to LA-taste
      mixtures. We recorded whole nerve responses from the CT in response to lingual
      application of LA with or without monosodium glutamate (MSG) in anesthetized male
      and female rats. In addition, we examined preferences for MSG + LA taste mixtures
      in behavioral tests. Although lingual application of LA alone did not produce CT
      whole nerve responses, coapplication of LA and MSG elicited greater CT responses
      than did MSG alone. These findings were paralleled by greater preferences for MSG
      + LA taste mixtures than for MSG alone. In both cases, the effect was
      particularly pronounced in male rats. Thus LA enhances CT activity and behavioral
      responses to LA + MSG taste mixtures, although there are sex differences in the
      effects. These results suggest that CT input is important in mediating behavioral
      responses to fat taste, but the effects depend upon other taste stimuli and
      differ in males and females.

PMID- 18635451
TI  - In vivo regulation of endothelium-dependent vasodilation in the rat renal
      circulation and the effect of streptozotocin-induced diabetes.
AB  - We assessed the relative contributions of endothelium-derived relaxing factors to
      renal vasodilation in vivo and determined whether these are altered in
      established streptozotocin-induced diabetes. In nondiabetic rats, stimulation of
      the endothelium by locally administered ACh or bradykinin-induced transient renal
      hyperemia. Neither basal renal blood flow (RBF) nor renal hyperemic responses to
      ACh or bradykinin were altered by blockade of prostanoid production
      (indomethacin) or by administration of charybdotoxin (ChTx) plus apamin to block
      endothelium-derived hyperpolarizing factor (EDHF). In contrast, combined blockade
      of nitric oxide (NO) synthase, N(omega)-nitro-l-arginine methyl ester (l-NAME),
      and prostanoid production reduced basal RBF and the duration of the hyperemic
      responses to ACh and bradykinin and revealed a delayed ischemic response to ACh.
      Accordingly, l-NAME and indomethacin markedly reduced integrated (area under the
      curve) hyperemic responses to ACh and bradykinin. Peak increases in RBF in
      response to ACh and bradykinin were not reduced by l-NAME and indomethacin but
      were reduced by subsequent blockade of EDHF. l-NAME plus indomethacin and ChTx
      plus apamin altered RBF responses to endothelium stimulation in a qualitatively
      similar fashion in diabetic and nondiabetic rats. The integrated renal hyperemic
      responses to ACh and bradykinin were blunted in diabetes, due to a diminished
      contribution of the component abolished by l-NAME plus indomethacin. We conclude
      that NO dominates integrated hyperemic responses to ACh and bradykinin in the rat
      kidney in vivo. After prior inhibition of NO synthase, EDHF mediates transient
      renal vasodilation in vivo. Renal endothelium-dependent vasodilation is
      diminished in diabetes due to impaired NO function.

PMID- 18635454
TI  - Mechanisms of neonatal increase in glomerular filtration rate.
AB  - To investigate the mechanisms responsible for the neonatal increase in glomerular
      filtration rate (GFR), renal function studies (whole kidney and micropuncture)
      were carried out in anesthesized fetal sheep (133-140 days gestation; term = 150
      days) and lambs (12-18 days). Fetuses were delivered and placed in a water bath
      (39.5 degrees C), keeping the umbilical cord moist and intact. Lambs were studied
      on a thermostatically controlled heating pad. Animals were prepared for either
      blood flow studies or micropuncture measurements. Expected differences in blood
      composition and cardiovascular and renal function were observed between fetuses
      and lambs, and values obtained for most variables were similar to those measured
      in chronically catheterized unanesthetized animals. Fetal GFR was much lower than
      that of lambs (0.20 vs. 0.62 ml.min(-1).g kidney(-1), P < 0.001). Free-flow, stop
      flow, and net filtration pressures (NFP) were lower in the fetuses than the lambs
      (NFP 20.8 vs. 23.8 mmHg, P < 0.001), as was the calculated ultrafiltration
      coefficient (0.014 vs. 0.022 ml.min(-1).g(-1).mmHg(-1), P < 0.001). Thus, we
      conclude that rises in both net filtration pressure and the ultrafiltration
      coefficient contribute to the large increase in GFR between fetal life and
      approximately 2 wk after birth.

PMID- 18635453
TI  - Responses of cardiac sympathetic nerve activity to changes in circulating volume
      differ in normal and heart failure sheep.
AB  - Factors controlling cardiac sympathetic nerve activity (CSNA) in the normal state
      and those causing the large increase in activity in heart failure (HF) remain
      unclear. We hypothesized from previous clinical findings that activation of
      cardiac mechanoreceptors by the increased blood volume in HF may stimulate
      sympathetic nerve activity (SNA), particularly to the heart via cardiocardiac
      reflexes. To investigate the effect of volume expansion and depletion on CSNA we
      have made multiunit recordings of CSNA in conscious normal sheep and sheep paced
      into HF. In HF sheep (n = 9) compared with normal sheep (n = 9), resting levels
      of CSNA were significantly higher (34 +/- 5 vs. 93 +/- 2 bursts/100 heart beats,
      P < 0.05), mean arterial pressure was lower (76 +/- 3 vs. 87 +/- 2 mmHg; P <
      0.05), and central venous pressure (CVP) was greater (3.0 +/- 1.0 vs. 0.0 +/- 1.0
      mmHg; P < 0.05). In normal sheep (n = 6), hemorrhage (400 ml over 30 min) was
      associated with a significant increase in CSNA (179 +/- 16%) with a decrease in
      CVP (2.7 +/- 0.7 mmHg). Volume expansion (400 ml Gelofusine over 30 min)
      significantly decreased CSNA (35 +/- 12%) and increased CVP (4.7 +/- 1.0 mmHg).
      In HF sheep (n = 6) the responses of CSNA to both volume expansion and hemorrhage
      were severely blunted with no significant changes in CSNA or heart rate with
      either stimulus. In summary, these studies in a large conscious mammal
      demonstrate that in the normal state directly recorded CSNA increased with volume
      depletion and decreased with volume loading. In contrast, both of these responses
      were severely blunted in HF with no significant changes in CSNA during either
      hemorrhage or volume expansion.

PMID- 18635452
TI  - High oxygen prevents fetal lethality due to lack of catecholamines.
AB  - The catecholamine norepinephrine is required for fetal survival, but its
      essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase
      (Th) null] mouse fetuses die at embryonic day (E)13.5-14.5, they resemble wild
      type (wt) fetuses exposed to hypoxia. They exhibit bradycardia (28% reduction in
      heart rate), thin ventricular myocardium (20% reduction in tissue), epicardial
      detachment, and death with vascular congestion, hemorrhage, and edema. At E12.5,
      before the appearance of morphological deficits, catecholamine-deficient fetuses
      are preferentially killed by experimentally induced hypoxia and have lower tissue
      Po(2) levels than wt siblings. By microarray analysis
      (http://www.ncbi.nlm.nih.gov/geo; accession no. GSE10341), hypoxia-inducible
      factor-1 target genes are induced to a greater extent in null fetuses than in wt
      siblings, supporting the notion that mutants experience lower oxygen tension or
      have an enhanced response to hypoxia. Hypoxia induces a 13-fold increase in
      plasma norepinephrine levels, which would be expected to increase heart rate,
      thereby improving oxygen delivery in wt mice. Surprisingly, increasing maternal
      oxygen (inspired O(2) 33 or 63%) prevents the effects of catecholamine
      deficiency, restoring heart rate, myocardial tissue, and survival of Th null
      fetuses to wt levels. We suggest that norepinephrine mediates fetal survival by
      maintaining oxygen homeostasis.

PMID- 18635455
TI  - Organization of metabolic pathways in vastus lateralis of patients with chronic
      obstructive pulmonary disease.
AB  - The objective of this study was to determine whether patients with chronic
      obstructive lung disease (COPD) display differences in organization of the
      metabolic pathways and segments involved in energy supply compared with healthy
      control subjects. Metabolic pathway potential, based on the measurement of the
      maximal activity (V(max)) of representative enzymes, was assessed in tissue
      extracted from the vastus lateralis in seven patients with COPD (age 67 +/- 4 yr;
      FEV(1)/FVC = 44 +/- 3%, where FEV(1) is forced expiratory volume in 1 s and FVC
      is forced vital capacity; means +/- SE) and nine healthy age-matched controls
      (age 68 +/- 2 yr; FEV(1)/FVC = 75 +/- 2%). Compared with control, the COPD
      patients displayed lower (P < 0.05) V(max) (mol.kg protein(-1).h(-1)) for
      cytochrome c oxidase (COX; 21.2 +/- 2.0 vs. 28.7 +/- 2.2) and 3-hydroxyacyl-CoA
      dehydrogenase (HADH; 2.54 +/- 0.14 vs. 3.74 +/- 0.12) but not citrate synthase
      (CS; 2.20 +/- 0.16 vs. 3.19 +/- 0.5). While no differences between groups were
      observed in V(max) for creatine phosphokinase, phosphorylase (PHOSPH),
      phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase, hexokinase
      (HEX) was elevated in COPD (P < 0.05). Enzyme activity ratios were higher (P <
      0.05) for HEX/CS, HEX/COX, PHOSPH/HADH and PFK/HADH in COPD compared with
      control. It is concluded that COPD patients exhibit a reduced potential for both
      the electron transport system and fat oxidation and an increased potential for
      glucose phosphorylation while the potential for glycogenolysis and glycolysis
      remains normal. A comparison of enzyme ratios indicated greater potentials for
      glucose phosphorylation relative to the citric acid cycle and the electron
      transport chain and glycogenolysis and glycolysis relative to beta-oxidation.

PMID- 18635456
TI  - A megalin-like receptor is involved in protein endocytosis in the midgut of an
      insect (Bombyx mori, Lepidoptera).
AB  - The mechanism responsible for fluorescein isothiocyanate (FITC)-albumin
      internalization by columnar cells in culture obtained from the midgut of Bombyx
      mori larvae was examined by confocal laser scanning microscopy. Protein uptake
      changed over time, and it appeared to be energy dependent, since it was strongly
      reduced by both low temperatures and metabolic inhibitors. Labeled albumin uptake
      as a function of increasing protein concentration showed a saturation kinetics
      with a Michaelis constant value of 2.0 +/- 0.6 microM. These data are compatible
      with the occurrence of receptor-mediated endocytosis. RT-PCR analysis and
      colocalization experiments with an anti-megalin primary antibody indicated that
      the receptor involved was a putative homolog of megalin, the multiligand
      endocytic receptor belonging to the low-density lipoprotein receptor family,
      responsible for the uptake of various molecules, albumin included, in many
      epithelial cells of mammals. This insect receptor, like the mammalian
      counterpart, required Ca(2+) for albumin internalization and was inhibited by
      gentamicin. FITC-albumin internalization was clathrin mediated, since two
      inhibitors of this process caused a significant reduction of the uptake, and
      clathrin and albumin colocalized in the intermicrovillar areas of the apical
      plasma membrane. The integrity of actin and microtubule organization was
      essential for the correct functioning of the endocytic machinery.

PMID- 18635457
TI  - Sex and gender in the perioperative period: wake up to reality.

PMID- 18635458
TI  - Sex, gender, and pain: "men are from Mars, women are from venus ...".

PMID- 18635459
TI  - Red-hot chili peppers: a spicy new approach to preventing postoperative pain.

PMID- 18635460
TI  - Mixed effect modeling in analgesia trials.

PMID- 18635461
TI  - Residual neuromuscular block: rediscovering the obvious.

PMID- 18635462
TI  - Patient-controlled analgesia: proxy-controlled analgesia?

PMID- 18635464
TI  - Pro: Newly appreciated pathophysiology of ischemic heart disease in women
      mandates changes in perioperative management.

PMID- 18635463
TI  - The role of postoperative neurocognitive dysfunction on quality of life for
      postmenopausal women 6 months after cardiac surgery.
AB  - BACKGROUND: Women are prone to neurological complications after cardiac surgery.
      We have previously reported that treatment perioperatively with the
      neuroprotectant steroid 17beta-estradiol did not improve neurocognitive end
      points 4 to 6 wk after surgery for elderly women. In this study, we evaluated the
      influence of early postoperative neurocognitive dysfunction on quality of life in
      postmenopausal women undergoing cardiac surgery and whether it is impacted by
      perioperative 17beta-estradiol treatment. METHODS: One hundred seventy-four
      postmenopausal women randomly received 17beta-estradiol or placebo in a double
      blind manner beginning the day before surgery and continued until the fifth
      postoperative day. The patients underwent psychometric testing using a standard
      battery before surgery and again 4 to 6 wk and 6 mo postoperatively. Quality of
      life was assessed at baseline and 6 mo after surgery with the SF-36 questionnaire
      and the Lawton instrumental activities of daily living scale. RESULTS: Complete
      data were available from 108 women of whom 13% demonstrated postoperative
      neurocognitive dysfunction. Based on multiple logistic regression analysis, a
      neurocognitive deficit 4 to 6 wk after surgery was an independent predictor of a
      lower SF-36 physical component score (P = 0.004) and lower Lawton instrumental
      activities of daily living scale 6 mo postoperatively (P = 0.026). Treatment with
      17beta-estradiol (P = 0.003) and smoking status (P = 0.015) were predictors of
      worse SF-36 mental health component rating. Preoperative lower scores were
      independently associated with low quality of life postoperatively for all
      measurements. CONCLUSIONS: Postoperative neurocognitive dysfunction is associated
      with impaired quality of life in women after cardiac surgery. Perioperative
      treatment with 17beta-estradiol provides no benefits to postoperative quality of
      life. The relationship between low preoperative and postoperative self-rated
      health status suggests that some aspects of quality of life in postmenopausal
      women are not amenable to improvements with cardiac surgery.

PMID- 18635465
TI  - Con: newly appreciated pathophysiology of ischemic heart disease in women
      mandates changes in perioperative management.

PMID- 18635466
TI  - Newly appreciated pathophysiology of ischemic heart disease in women mandates
      changes in perioperative management: a core review.
AB  - The assumption that males and females are physiologically similar has led to
      females being clinically evaluated and treated as males. However, there is
      growing evidence in the literature that, other than the reproductive system,
      there are other fundamental physiological differences between the two genders.
      The manifestation of these differences starts soon after puberty and becomes more
      pronounced with age. The differences in body mass and volume and renal and liver
      metabolism account for the difference in therapeutic efficacy and side effects of
      commonly used cardiovascular drugs. Women have smaller coronary arteries, more
      frequent diastolic dysfunction, present with vague symptoms of coronary artery
      disease and do worse than men after revascularization procedures. Women also have
      a shorter cardiac cycle and are more prone to develop arrhythmias and react
      differently to antiarrhythmic drugs. Most epidemiological trials that have
      assessed the utility of pharmacological myocardial protection or outcomes after
      noncardiac surgery have either been performed on men only or women were not
      identified as a separate group. Recent evidence is suggestive that coronary
      vasospasm may be the dominant etiology of acute myocardial ischemia in women.
      This may explain the poor sensitivity and specificity of the routine myocardial
      perfusion tests. Having considered all this evidence, it has become very
      essential to view the operative risk stratification as being gender-based. This
      approach may involve a shift in our present day paradigm of patient management.

PMID- 18635467
TI  - Dynamic tight glycemic control during and after cardiac surgery is effective,
      feasible, and safe.
AB  - BACKGROUND: Tight blood glucose control reduces mortality and morbidity in
      critically ill patients, but intraoperative glucose control during cardiac
      surgery is often difficult, and risks hypoglycemia. In this study, we evaluated
      the safety and efficacy of a nurse-driven insulin protocol (the Aalst Glycemia
      Insulin Protocol) for achieving a target glucose level of 80-110 mg/dL during
      cardiac surgery and in the intensive care unit (ICU). METHODS: We included 483
      nondiabetics and 168 diabetics scheduled for cardiac surgery with cardiopulmonary
      bypass. To anticipate rapid perioperative changes in insulin requirement and/or
      sensitivity during surgery, we developed a dynamic algorithm presented in tabular
      form, with rows representing blood glucose ranges and columns representing
      insulin dosages based on the patients' insulin sensitivity. The algorithm adjusts
      insulin dosage based on blood glucose level and the projected insulin sensitivity
      (e.g., reduced sensitivity during cardiopulmonary bypass and normalizing
      sensitivity after surgery). RESULTS: A total of 18,893 blood glucose measurements
      were made during and after surgery. During surgery, the mean glucose level in
      nondiabetic patients was within targeted levels except during (112 +/- 17 mg/dL)
      and after rewarming (113 +/- 19 mg/dL) on cardiopulmonary bypass. In diabetics,
      blood glucose was decreased from 121 +/- 40 mg/dL at anesthesia induction to 112
      +/- 26 mg/dL at the end of surgery (P < 0.05), with 52.9% of patients achieving
      the target. In the ICU, the mean glucose level was within targeted range at all
      time points, except for diabetics upon ICU arrival (113 +/- 24 mg/dL). Of all
      blood glucose measurements (operating room and ICU), 68.0% were within the
      target, with 0.12% of measurements in nondiabetics and 0.18% in diabetics below
      60 mg/dL. Hypoglycemia < 50 mg/dL was avoided in all but four (0.6%) patients (40
      mg/dL was the lowest observed value). CONCLUSIONS: The Aalst Glycemia Insulin
      Protocol is effective for maintaining tight perioperative blood glucose control
      during cardiac surgery with minimal risk of hypoglycemia.

PMID- 18635469
TI  - The prevalence of and risk factors for adverse events in children receiving
      patient-controlled analgesia by proxy or patient-controlled analgesia after
      surgery.
AB  - BACKGROUND: Recent reports emphasize the risks associated with patient-controlled
      analgesia by proxy (PCA-P), yet data regarding such risks in children remain
      sparse. We compared the prevalence of clinically significant adverse events in
      children receiving PCA-P versus PCA, and examined factors that place children at
      increased risk. METHODS: The records were reviewed of opioid-naive children, ages
      birth to 18 yr, who received PCA or PCA-P after surgery. Data included
      demographics, comorbidities, perioperative information, pain, sedation, and
      respiratory assessments, oxygen saturation, analgesics, adverse outcomes, and
      interventions. RESULTS: This study included 145 children who received PCA-P and
      157 PCA. The PCA-P group was younger and had more comorbidities (P < 0.05).
      Opioid orders were similar, but pain scores and opioid dosages were lower, and
      fewer children received diazepam in the PCA-P group (P < 0.05). Clinically
      significant adverse events (i.e., those requiring intervention) occurred in 22%
      and 24% of patients in the PCA-P and PCA groups, respectively; however, more
      children in the PCA group had "threshold events" (minor intervention) and more in
      the PCA-P group had "rescue events" (opioid reversal or escalation of level of
      care). Respiratory events occurred earlier in the PCA-P group (P < 0.05). Factors
      associated with adverse events included orthopedic surgery, cognitive impairment,
      respiratory comorbidity, use of continuous basal opioid infusion, use of
      diazepam, and larger opioid doses on days 1, 2, and 3. Yet, cognitive impairment
      and opioid dose on day 1 were the only factors independently predictive of these
      events. CONCLUSIONS: This study found that although a significant number of
      children receiving PCA and PCA-P experienced adverse events, there was no
      difference in the prevalence between groups. The PCA-P group was at greater risk
      for events requiring rescue interventions, perhaps due to the prevalence of
      underlying comorbidities. These findings emphasize the need for vigilant
      monitoring to facilitate early recognition and timely intervention of respiratory
      depression.

PMID- 18635468
TI  - Treatment of acute postoperative hypertension in cardiac surgery patients: an
      efficacy study of clevidipine assessing its postoperative antihypertensive effect
      in cardiac surgery-2 (ESCAPE-2), a randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Acute postoperative hypertension is a well-known complication of
      cardiac surgery and is associated with postoperative morbidity. Clevidipine, an
      ultrashort-acting, third-generation dihydropyridine calcium channel blocker,
      exerts vascular-selective, arterial-specific vasodilation to decrease arterial
      blood pressure without negatively impacting cardiac function. In this double
      blind, placebo-controlled trial, we examined the efficacy and safety of
      clevidipine in treating postoperative hypertension in cardiac surgery patients.
      METHODS: Two hundred six patients undergoing cardiac surgery were randomized
      preoperatively. Of these, 110 met postrandomization inclusion criteria for the
      study [systolic blood pressure (SBP) >or=140 mm Hg within 4 h of admission to a
      postoperative setting, and clinically assessed as needing SBP reduction by
      >or=15% from baseline]. Patients received an infusion of either clevidipine (0.4
      8.0 microg kg(-1) min(-1)) or 20% lipid emulsion (placebo) for 30 min to a
      maximum of 1 h unless treatment failure occurred sooner. The primary end point
      was the incidence of treatment failure, defined as the inability to decrease SBP
      by >or=15% from baseline, or the discontinuation of study treatment for any
      reason within the 30-min period after study drug initiation. RESULTS: Clevidipine
      treated patients had a significantly lower incidence of treatment failure than
      placebo patients [8.2% (5 of 61) vs 79.6% (39 of 49), P < 0.0001]. Treatment
      success was achieved in 91.8% of clevidipine-treated patients. Median time to
      target SBP with clevidipine was 5.3 min (95% confidence interval, 4-7 min). No
      clinically significant increase in heart rate from baseline was observed. Adverse
      event rates were similar for both treatment groups. CONCLUSIONS: Clevidipine is
      effective and safe in the rapid treatment of acute postoperative hypertension
      after cardiac surgery.

PMID- 18635470
TI  - Listening to music during anesthesia does not reduce the sevoflurane
      concentration needed to maintain a constant bispectral index.
AB  - BACKGROUND: Music reduces stress responses in awake subjects. However, there
      remains controversy about the role of music or therapeutic suggestions during
      general anesthesia and postoperative recovery. We thus tested the hypothesis that
      intraoperative exposure to soothing music reduces the end-tidal concentration of
      sevoflurane (ETSevo) necessary to maintain bispectral index (BIS) near 50 during
      laparoscopic surgery. METHODS: Forty patients, aged 40-60 yrs, ASA I and II,
      undergoing laparoscopic hernias or cholecystectomy under general anesthesia were
      studied. All patients were connected to a BIS monitor. Anesthesia was induced
      with fentanyl 2 microg/kg, sevoflurane in oxygen, rocuronium (0.6 mg/kg), and
      maintained with sevoflurane in oxygen and 50% nitrous oxide, with an infusion of
      fentanyl (1 microg x kg(-1) x h(-1)). Sevoflurane was titrated to maintain BIS
      near 50 throughout the procedure. Patients were randomly assigned to either
      listen to music or not. RESULTS: The ETSevo necessary to maintain a BIS near 50
      was virtually identical in patients who listened to music (1.29 +/- 0.33%) and
      those who did not (1.27 +/- 0.33%, P = 0.84). Patients who listened to music
      reported slightly less pain, but the difference was not statistically
      significant. Mean arterial blood pressure was slightly higher in patients who
      listened to music (101 +/- 11 mm Hg) than in those who did not (94 +/- 10 mm Hg,
      P = 0.040). CONCLUSIONS: The end-tidal concentration of sevoflurane required to
      maintain BIS near 50 during laparoscopic cholecystectomy was virtually identical
      in patients exposed to music or not. Although previous work suggests that music
      reduces preoperative stress and may be useful during sedation, our results do not
      support the use of music during surgery.

PMID- 18635471
TI  - Sex-specific responses to opiates: animal and human studies.
AB  - It is widely reported that analgesic drugs acting at mu, kappa, and delta opioid
      receptors display quantitative and qualitative differences in effect in males and
      females. These sex-related differences are not restricted to the
      analgesic/antinociceptive properties of opioids, but are also present in opioid
      induced side effects, such as changes in respiration, locomotor activity,
      learning/memory, addiction, and changes in the cardiovascular system. An
      increasing number of well-controlled animal and human studies directly examining
      the issue of sex in the potency of opioids show that, although sex may affect
      opioid analgesia, the direction and magnitude of sex differences depend on many
      interacting variables. These include those specific to the drug itself, such as
      dose, pharmacology, and route and time of administration, and those particular to
      the subject, such as species, type of pain, genetics, age, and gonadal/hormonal
      status. In the current review, we systematically present these animal and human
      studies and discuss the data in relation to the depending variables. Although the
      observed sex differences in opioid effect may be clinically relevant, lack of
      knowledge on other factors involved in the large variability in patient opioid
      analgesic sensitivity should compel practitioners to customize their dosing
      regimens based on individual requirements.

PMID- 18635472
TI  - Dexmedetomidine enhances the local anesthetic action of lidocaine via an alpha-2A
      adrenoceptor.
AB  - BACKGROUND: Clonidine, an alpha-2 adrenoceptor agonist, is a common adjunct in
      both central and peripheral blocks. Dexmedetomidine, a more selective alpha-2
      adrenoceptor agonist, is also known to enhance central neural blockades. Its
      peripheral effect, however, has not been fully elucidated. Thus, we evaluated the
      effect of dexmedetomidine and other alpha-2 adrenoceptor agonists on the local
      anesthetic action of lidocaine at the periphery and explored the mechanism
      involved. METHODS: alpha-2 Adrenoceptor agonists, including dexmedetomidine,
      clonidine, and oxymetazoline, combined with lidocaine were intracutaneously
      injected into the back of male guinea pigs. The test of six pinpricks was applied
      every 5 min until 60 min after the injection. The number of times which the prick
      failed to elicit a response during the 60-min period was added and the sum served
      as an anesthetic score indicating the degree of local anesthesia. Differences
      from the control value within the group were analyzed using an analysis of
      variance followed by a post hoc Dunnett's test. Furthermore, we evaluated the
      antagonism of the effect of dexmedetomidine by yohimbine, an alpha-2A, 2B, and 2C
      adrenoceptor antagonist, or prazosin, an alpha-1, alpha-2B, and 2C adrenoceptor
      antagonist, analyzed using a two-way analysis of variance. RESULTS: All alpha-2
      adrenoceptor agonists enhanced the degree of local anesthesia of lidocaine in a
      dose-dependent manner. Furthermore, yohimbine inhibited the effect of
      dexmedetomidine, whereas prazosin did not. CONCLUSION: We demonstrated that alpha
      2 adrenoceptor agonists enhanced the local anesthetic action of lidocaine, and
      suggest that dexmedetomidine acts via alpha-2A adrenoceptors.

PMID- 18635473
TI  - Propofol sedation is reduced by delta9-tetrahydrocannabinol in mice.
AB  - BACKGROUND: Delta9-tetrahydrocannabinol (Delta9-THC) induces analgesic effects
      and alterations of alertness. It has been reported that propofol increases
      endocannabinoid levels in the brain, but the effects of Delta9-THC on propofol
      sedation remain unclear. Our aim was to characterize the interaction between
      Delta9-THC and propofol in terms of sedation and analgesia. METHODS: Sedation was
      monitored by a rota-rod and analgesia by tail-flick latencies. Twenty mice
      received intraperitoneal injections of 50 mg/kg Delta9-THC with 50, 75 and 100
      mg/kg propofol after baseline values were established for each drug. Control
      experiments were performed with Delta9-THC and thiopental or Intralipid. RESULTS:
      Injection of 50 mg/kg propofol caused a rapid onset of sedation with a minimum of
      24 s on the rota-rod. Fifty mg/kg Delta9-THC alone had no sedative effects.
      Administration of Delta9-THC significantly reduced the sedative effect of
      propofol to at least 60 s on the rota-rod (P < 0.001). After increasing the
      propofol dose to 100 mg/kg in the presence of Delta9-THC, sedation was re
      established with 27 s on the rota-rod. Thiopental sedation was significantly
      reduced (P < 0.01) in the presence of Delta9-THC. CONCLUSION: The results
      indicate a dose-dependent antagonistic interaction between Delta9-THC and
      propofol, and also between Delta9-THC and thiopental.

PMID- 18635474
TI  - The effects of fentanyl-like opioids and hydromorphone on human 5-HT3A receptors.
AB  - BACKGROUND: 5-HT(3) receptors are involved in various physiologic functions,
      including the modulation of emesis. 5-HT(3) antagonists are clinically widely
      used as potent antiemetics. Emesis is also a side effect of opioid analgesics.
      Intriguingly, the natural opioid morphine shows specific interactions with human
      5-HT(3) receptors at clinically relevant concentrations. In the present study, we
      investigated whether this is a general effect of opioids, even when they are
      structurally diverse. Therefore, another morphine (phenanthrene-type) derivative,
      hydromorphone, and fentanyl including its (4-anilinopiperidine-type) derivatives
      were tested. METHODS: Whole-cell patches from human embryonic kidney-293 cells,
      stably transfected with the human 5-HT(3A) receptor cDNA, were used to determine
      the opioid effects on the 5-HT (3 microM)-induced currents using the patch clamp
      technique (voltage-clamp). RESULTS: None of the fentanyl derivatives affected
      currents through the 5-HT(3A) receptor (3 microM 5-HT) significantly in the
      clinically relevant nanomolar concentration range (IC(50) values >30 microM). In
      contrast, hydromorphone was considerably more potent (IC(50) = 5.3 microM),
      slowing the current activation- and desensitization-kinetics significantly (at 3
      microM by a factor of 1.9 and 2.4, respectively), similar to morphine. At
      concentrations much higher than clinically relevant, but within the range
      predicted from Meyer-Overton correlations for nonspecific interactions, the
      fentanyl derivatives all showed at least a tendency to suppress current
      amplitudes, but they had diverse effects on the activation- and desensitization
      kinetics of 5-HT(3A) receptors. CONCLUSIONS: Only morphine and hydromorphone, but
      not the fentanyl derivatives, reduced 5-HT-induced current amplitudes and slowed
      current kinetics near clinically relevant concentrations. The high potencies of
      morphine and hydromorphone, when compared to their lipophilicities, suggest a
      specific interaction with 5-HT(3A) receptors. In contrast, the effects of
      fentanyl-type opioids appear to be of unspecific nature. Because the rank order
      of opioid potencies for human 5-HT(3A) receptors is opposite of that for opioid
      receptors, the site involved is structurally different from opioid receptor
      binding sites. In agreement with recent data on different phenols, a phenolic OH
      group (which morphine and hydromorphone possess) may contribute to specific
      interactions of morphine and hydromorphone with the 5-HT(3A) receptor. Future
      clinical studies could test whether corresponding differences in emetogenicity
      between different classes of opioids will be found.

PMID- 18635475
TI  - The onset time of atracurium is prolonged in patients with sickle cell disease.
AB  - BACKGROUND: Patients with sickle cell disease (SCD) frequently undergo surgery
      during their lifetime. Patients with SCD are considered at greater risk of
      perioperative complications than otherwise healthy patients and require
      meticulous anesthetic management. The pharmacodynamics of anesthetics may be
      altered in patients with SCD due to microcirculatory abnormalities or anemia.
      METHODS: In this study, we assessed the pharmacodynamics of a single dose of
      atracurium (0.5 mg/kg) by mechanomyography in 13 patients with SCD and in 17
      control patients. RESULTS: The time between atracurium administration and 90%
      twitch height depression (onset time) was longer in SCD patients (mean +/- sd)
      323 +/- 124 s than in controls 165 +/- 36 s (P < 0.01). Unsatisfactory intubation
      conditions at 3 min after atracurium administration were observed in 5/13
      patients with SCD and 1/17 control patients (P < 0.05). The duration of action of
      atracurium in patients with SCD was similar to that of control patients. The time
      to spontaneous return of the train-of-four ratio to 0.9 was 101 +/- 24 min in
      control patients and did not differ 93 +/- 24 min in patients with SCD.
      CONCLUSION: Delayed onset time, together with unchanged duration of the
      neuromuscular blocking effect of atracurium, may be explained by an increased
      distribution volume of atracurium in patients with SCD. Our results suggest that
      monitoring of neuromuscular block may guide the time of tracheal intubation in
      patients with SCD.

PMID- 18635476
TI  - Variability comparison of the composite auditory evoked potential index and the
      bispectral index during propofol-fentanyl anesthesia.
AB  - BACKGROUND: Monitors of hypnotic depth help anesthesiologists to guide the
      anesthetic. The performance of different monitors depends on several factors,
      index variability at a steady state of hypnotic depth being one. We compared the
      recently introduced AAI1.6 with the established bispectral index (BIS), regarding
      index variability during stable values of propofol effect-site concentration.
      METHODS: After ethics committee approval and written informed consent, anesthesia
      was performed in 40 patients with propofol as the target controlled infusion and
      fentanyl. Variability of BIS and AAI1.6 was calculated during periods of constant
      predicted propofol effect compartment concentration and constant levels of
      surgical stimulation as the median absolute deviation (MAD) from the median
      value. A variability index was calculated as 1.48*MAD/(threshold - median value),
      with threshold being the division line between awake and asleep. Threshold
      crossing time was used to evaluate the performance in predicting return of
      consciousness. RESULTS: Variability index, however, was significantly larger for
      the AAI1.6, despite similar absolute variability measured as MAD. Lightening of
      anesthesia before recovery could be noticed earlier using the BIS than the
      AAI1.6, although consciousness was detected with a significantly higher Pk-value
      by the AAI1.6. CONCLUSION: Variability in relation to the difference between the
      median index value during anesthesia and the threshold necessary to detect
      consciousness with high sensitivity is higher for the AAI1.6 than for the BIS.
      This, as well as the steeper concentration-response function found for AAI1.6,
      impairs the performance of the AAI1.6 in predicting imminent return of
      consciousness during decreasing propofol concentrations. However, it makes AAI1.6
      well suited to detect consciousness when it has occurred.

PMID- 18635477
TI  - An evaluation of a new combined Spo2/PtcCO2 sensor in very low birth weight
      infants.
AB  - BACKGROUND: Recently, a new sensor for combined assessment of pulse oximetry
      oxygen saturation (Spo(2)) and transcutaneous monitoring of carbon dioxide
      partial pressure (PtcCO(2)) has been introduced (TOSCA 500, Radiometer basel AG,
      Switzerland) [corrected] We designed this study to evaluate the usability and
      reliability of TOSCA in neonates with birth weight <or=1500 g (very low birth
      weight). METHODS: In a prospective study of 22 newborns, TOSCA was tested,
      positioning the sensor on the ear pinna with an adhesive attachment clip.
      Simultaneous monitoring with TOSCA, conventional pulse oximeter (HP; Datex Ohmeda
      3740), and a transcutaneous device (TINA TCM3, Radiometer, Copenhagen) was
      performed for 60 min. PtcCO(2) measurement from TOSCA (PtcCO(2TOSCA)) and TINA
      (PtcCO(2)) were compared with Pco(2) from blood samples (PCO(2EAB)) at 1 and 60
      min. During the monitoring period, values of PtcCO(2TOSCA) were compared with
      PtcCO(2), and SatO(2) values from TOSCA with those from a pulse oximeter.
      Corresponding data were compared using Bland-Altman analysis. RESULTS: Bias
      (precision) at 1 min and at 60 min between PCO(2EAB) and PtcCO(2) values were 3.5
      (12.4) mm Hg and 2.8 (10.2), respectively, whereas between PCO(2EAB) and
      PtcCO(2TOSCA) values were 18.3 (30.4) mm Hg and 1.8 (25) mm Hg. Bland-Altman
      analysis shows a better correspondence PtcCO(2)/PtcCO(2TOSCA) between 7 and 15
      min. No significant differences were found between Spo(2) and SpO(2TOSCA).
      CONCLUSIONS: The TOSCA monitor is safe and easy to apply in very low birth weight
      newborns. The pulse oximeter measurements may be useful for titrating oxygen
      therapy. Pco(2) measurement with TOSCA is most useful as a trend and independent
      confirmation of arterial Pco(2) is required if an accurate value is needed.

PMID- 18635478
TI  - Residual neuromuscular blockade and critical respiratory events in the
      postanesthesia care unit.
AB  - BACKGROUND: Incomplete recovery of neuromuscular function may impair pulmonary
      and upper airway function and contribute to adverse respiratory events in the
      postanesthesia care unit (PACU). The aim of this investigation was to assess and
      quantify the severity of neuromuscular blockade in patients with signs or
      symptoms of critical respiratory events (CREs) in the PACU. METHODS: We collected
      data over a 1-yr period. PACU nurses identified patients with evidence of a
      predefined CRE during the first 15 min of PACU admission. Train-of-four (TOF)
      ratios were immediately quantified in these patients using acceleromyography
      (cases). TOF data were also collected in a control group that consisted of
      patients undergoing a general anesthetic during the same period who were matched
      with the cases by age, sex, and surgical procedure. RESULTS: A total of 7459
      patients received a general anesthetic during the 1-yr period, of whom 61
      developed a CRE. Forty-two of these cases were matched with controls and
      constituted the study group for statistical analysis. The most common CREs among
      matched cases were severe hypoxemia (22 of 42 patients; 52.4%) and upper airway
      obstruction (15 of 42 patients; 35.7%). There were no significant differences
      between the cases and matched controls in any measured preoperative or
      intraoperative variables. Mean (+/-sd) TOF ratios were 0.62 (+/-0.20) in the
      cases, with 73.8% of the cases having TOF ratios <0.70. In contrast, TOF values
      in the controls were 0.98 (+/-0.07) (a difference of -0.36 with a 95% confidence
      interval of -0.43 to -0.30, P < 0.0001), and no control patients were observed to
      have TOF values <0.70 (the 95% confidence interval of the difference was 59%-85%,
      P < 0.0001). CONCLUSIONS: A high incidence of severe residual blockade was
      observed in patients with CREs, which was absent in control patients without
      CREs. These findings suggest that incomplete neuromuscular recovery is an
      important contributing factor in the development of adverse respiratory events in
      the PACU.

PMID- 18635479
TI  - Postoperative hypoxemia in morbidly obese patients with and without obstructive
      sleep apnea undergoing laparoscopic bariatric surgery.
AB  - INTRODUCTION: The increased incidence of morbid obesity has resulted in an
      increase of bariatric surgical procedures. Obstructive sleep apnea (OSA) is a
      commonly encountered comorbidity in morbidly obese patients. Sedatives,
      analgesics, and anesthetics alter airway tone, and airway obstruction and death
      have been reported in patients with OSA after minimal doses of sedatives and
      anesthetics, yet there is a lack of consensus regarding the care of these
      patients. In this study, we sought to determine whether obese patients with
      polysomnography-confirmed diagnosis of OSA were at significantly greater risk for
      postoperative hypoxemic episodes in the first 24 h after laparoscopic bariatric
      surgery than morbidly obese patients without a diagnosis of OSA. METHODS: Adult
      subjects (Body Mass Index, 35-75 kg/m(2)) scheduled to undergo laparoscopic
      bariatric surgery were studied. A finger pulse oximetry probe was placed
      preoperatively and oxygen saturation (Spo(2)) was recorded continuously. All
      subjects underwent preoperative polysomnography testing within 4 wk of surgery.
      Anesthetic management was standardized, using propofol for induction and
      desflurane and remifentanil for maintenance of anesthesia. Patient-controlled
      analgesia programmed to deliver morphine, 1 mg. every 10 minutes, was used for
      pain management postoperatively. Hypoxemic episodes were scored as Spo(2) >4%
      below the polysomnography study baseline and lasting for more than 10 s. RESULTS:
      Eight men and 32 women were enrolled and 1 subject had incomplete data. Thirty
      one of the 40 subjects had polysomnography-confirmed OSA. Eight subjects used
      home continuous positive airway pressure devices nightly, and six of these used
      their device postoperatively. Preoperatively, subjects with OSA had lower nadir
      Spo(2) during the polysomnography study and a larger number had an apnea/hypopnea
      index >10 episodes per hour compared with the non-OSA group. In the first 24 h
      postoperatively, there was no difference in the median Spo(2) with and without
      oxygen therapy, between OSA and non-OSA groups. The number of episodes of oxygen
      desaturation >4% below the polysomnography study baseline value and the mean
      number of desaturation episodes per hour did not differ between the groups.
      CONCLUSIONS: In morbidly obese subjects, in the first 24 h after laparoscopic
      bariatric surgery, OSA does not seem to increase the risk of postoperative
      hypoxemia. Our data confirm that morbidly obese subjects, with or without OSA,
      experience frequent oxygen desaturation episodes postoperatively, despite
      supplemental oxygen therapy suggesting that perioperative management strategies
      in morbidly obese patients undergoing laparoscopic bariatric surgery should
      include measures to prevent postoperative hypoxemia.

PMID- 18635480
TI  - A comparison of glidescope videolaryngoscopy to direct laryngoscopy for
      nasotracheal intubation.
AB  - BACKGROUND: In this study, we compared the effectiveness of direct laryngoscopy
      (DL) and the GlideScope videolaryngoscope (GVL) for nasotracheal intubation, as
      judged by the time to intubation (TTI-the primary outcome) and the ease of
      intubation. METHODS: Seventy patients requiring nasotracheal intubation for
      elective surgery were randomly allocated to intubation with the GVL or DL. TTI
      was assessed by a blinded observer. Operators were blinded until the start of
      laryngoscopy. A Visual Analog Scale assessed the ease of intubation. The number
      of intubation attempts, number of failures, glottic grades, amount of bleeding,
      usage of Magill forceps, and the severity of postoperative sore throat were
      recorded. RESULTS: The median TTI was 23.2 s faster with the GVL (43.5 s,
      interquartile range [IQR]: 39.8-67.3) than with DL (66.7 s, IQR: 53.8-89.9), P =
      0.0023. Nasotracheal intubation was easier with the GVL than with DL (Visual
      Analog Scale 10 mm, IQR: 5.5-18, vs 20 mm, IQR: 10-32, P = 0.0041). The incidence
      of postoperative moderate or severe sore throat was significantly reduced in the
      GVL group (9% vs 34%, P = 0.018). Glottic exposure was significantly better with
      the GVL. Magill forceps were not used in the GVL group, but were used 49% of the
      time in the DL group, P < 0.0001. The incidence and severity of bleeding were
      similar between groups. CONCLUSIONS: Compared with DL, the GVL has superior
      performance characteristics when used for nasotracheal intubation and
      demonstrates an important reduction of postoperative sore throat. The GVL has a
      clear role in routine nasotracheal intubation.

PMID- 18635481
TI  - The ankle-to-arm blood pressure index predicts risk of cardiac complications
      after noncardiac surgery.
AB  - BACKGROUND: Peripheral arterial disease, as detected by a reduced ankle-to-arm
      blood pressure index (AAI), has been shown to predict future cardiac events.
      However, the utility of measuring the AAI to predict postoperative cardiac
      complications in patients undergoing noncardiac surgery is unknown. METHODS: We
      prospectively studied 242 consecutive patients aged 50 yr or older presenting to
      a university hospital preadmission clinic before elective noncardiac surgery. We
      performed a standardized clinical evaluation that included calculation of the
      revised cardiac risk index (rCRI) and measurement of the AAI using both palpation
      and Doppler techniques. Independent observers, blinded to preoperative assessment
      and AAI results, ascertained cardiac complications in the first 7 days after
      surgery. We assessed the ability of an abnormal AAI (<or=0.9 or absence of all
      four pedal pulses) to predict postoperative cardiac complications using
      likelihood ratios (LR), area under the ROC curves (AUC), and multivariable
      logistic regression in which we adjusted for the rCRI result. RESULTS: The cohort
      had a median age of 67 yr, 60% were male, 19% had diabetes, 14% had ischemic
      heart disease, and 35% underwent intraperitoneal or intrathoracic surgery.
      Postoperatively, 14 of 242 (6%) patients suffered cardiac complications, but no
      patients died. An abnormal AAI was present in 44 patients, 10 (23%) of whom had
      postoperative cardiac complications: positive LR 4.79 (95% CI: 3.04-7.54),
      negative LR 0.34 (95% CI: 0.15-0.77), AUC = 0.80. The AAI compared favorably with
      the rCRI, which had positive LR 4.22 (95% CI: 2.24-7.95), negative LR 0.57 (95%
      CI: 0.34-0.96), and AUC = 0.74. In multivariate analysis, the adjusted odds ratio
      for having a cardiac complication was 10.16 (95% CI: 2.90-36.02) for those
      patients with an abnormal AAI, even after adjusting for rCRI results.
      CONCLUSIONS: An abnormally low AAI, indicative of underlying peripheral arterial
      disease, is an independent risk factor for postoperative cardiac complications.
      The accuracy of the AAI is similar to the rCRI, and it provides additional
      independent predictive value for preoperative cardiac risk stratification.

PMID- 18635482
TI  - A prospective randomized trial of two safety peripheral intravenous catheters.
AB  - BACKGROUND: To reduce the risk of accidental needlestick injuries, first active
      then passive safety devices were developed on IV catheters. However, whether
      these catheters are easy to implement and really protect personnel from
      accidental needlestick is untested. METHODS: In this prospective randomized
      survey, we compared a passive safety catheter with an active safety catheter and
      a nonsafety classic catheter. The main objective was to evaluate the difficulty
      of inserting the catheters in terms of the number of insertion failures,
      difficulties introducing the catheter and withdrawing the needle, and the
      normality of the blood reflux in the delivery system. The second objective was to
      determine the degree of exposure to patients' blood evaluated as the number of
      exposures of the staff and blood splashes of the environment, and the staff's
      sense of protection. RESULTS: Seven hundred fifty-nine assessment cards were
      collected. The number of failures for the three catheter groups was similar and
      not statistically different. Introduction of the catheter was more difficult with
      the active safety catheter. Needle withdrawal was more difficult with the passive
      safety catheter. The blood reflux was abnormal more often with the safety
      catheters. The staff's exposure was more frequent with the active safety
      catheter. The number of blood splashes was more common with the safety catheters.
      CONCLUSIONS: Safety catheters are not superior with regard to failure rate in the
      catheter's placement. Users feel better protected, but find the use of safety
      catheters more difficult, and their handling generates more splashing of blood
      into the environment. The passive safety catheter is more efficient than the
      active safety catheter with regard to ease of introduction of the catheter into
      the vein and the staff's exposure to the patient's blood.

PMID- 18635483
TI  - Sex steroids/receptor antagonist: their use as adjuncts after trauma-hemorrhage
      for improving immune/cardiovascular responses and for decreasing mortality from
      subsequent sepsis.
AB  - Studies in human as well as animal models demonstrate that females in the
      proestrus cycle (i.e., with high estrogen) tolerate trauma-hemorrhage and sepsis
      far better than males. The female sex steroid, estrogen, is the significant
      factor contributing to this observed gender difference in outcome. One reason for
      the lack of significant gender association in some clinical studies is the
      possibility of heterogeneity of the population in terms of their hormonal status
      at the time of injury. Several experimental investigations have revealed that
      androgens produce immune and cardiovascular depression after trauma-hemorrhage.
      However, the use of an androgen receptor antagonist after trauma-hemorrhage has
      salutary effects of immune and cardiovascular function. Likewise, estrogen
      produces beneficial effects on immune and cardiovascular function after trauma
      hemorrhage and significantly decreases mortality rates from subsequent sepsis.
      The salutary effects of estrogen after trauma-hemorrhage have been shown to be
      due to both genomic and nongenomic effects. Thus, the use of an estrogen or
      androgen receptor antagonist as an adjunct after trauma-hemorrhage is a safe and
      novel approach for restoring immune and cardiovascular function after trauma
      hemorrhage and for decreasing the mortality from subsequent sepsis.

PMID- 18635484
TI  - The efficacy of dexmedetomidine in patients with noninvasive ventilation: a
      preliminary study.
AB  - BACKGROUND: Agitation is associated with failure of noninvasive ventilation
      (NIV). We investigated the effect of dexmedetomidine in patients with NIV.
      METHODS: This was a prospective clinical investigation in an intensive care unit.
      Dexmedetomidine was infused in 10 patients in whom NIV was difficult because of
      agitation. RESULTS: Ramsay and Richmond Agitation-Sedation Scale scores were
      maintained at 2.94 +/- 0.94 and -1.23 +/- 1.30, respectively. All patients were
      successfully weaned from NIV, and the respiratory state was not worsened.
      CONCLUSION: This study shows that dexmedetomidine is an effective sedative drug
      for patients with NIV.

PMID- 18635485
TI  - Sevoflurane and the feto-placental vasculature: the role of nitric oxide and
      vasoactive eicosanoids.
AB  - BACKGROUND: The effects and mechanisms of action of volatile anesthetics on the
      feto-placental vasculature are not known. We aimed to quantify the vasoactive
      effects of sevoflurane and determine the role of nitric oxide (NO) and of
      vasoactive eicosanoids in mediating these effects in isolated human chorionic
      plate arterial rings. METHODS: Quadruplicate ex vivo human chorionic plate
      arterial rings were used in all studies. Series 1 quantified the vasodilation
      produced by sevoflurane in rings preconstricted with the thromboxane analog
      U46619. Series 2A-C examined the role of NO in sevoflurane-mediated vasodilation.
      In separate experiments, we examined the potential for the nonspecific NO
      inhibitors, L-NAME, L-nMMA, and the inactive D-NAME, to modulate the vasodilation
      produced by sevoflurane. Series 2D determined whether sevoflurane altered
      vascular smooth muscle sensitivity to exogenous NO. Series 3A-D examined the role
      of vasoactive eicosanoids in sevoflurane-mediated vasodilation. In separate
      experimental series, we examined whether the nonspecific cyclooxygenase
      inhibitor, indomethacin, or the 5-lipoxygenase inhibitor, nordihydroguaiaretic
      acid, modulated sevoflurane-mediated vasodilation. RESULTS: Sevoflurane produced
      dose-dependent vasodilation of preconstricted chorionic plate arterial rings,
      with mean ring vasodilation increasing from 15 +/- 7% at 2% sevoflurane to 67 +/-
      17% (mean +/- sd) at 8% sevoflurane. Blockade of NO synthase did not attenuate
      the vasodilator effects of sevoflurane. Sevoflurane did not alter smooth muscle
      sensitivity to NO. Indomethacin augmented sevoflurane vasodilation at 10(-5) M,
      but not at 10(-6) M. Conversely, nordihydroguaiaretic acid attenuated sevoflurane
      mediated vasodilation at 3 x 10(-6) M but not at 3 x 10(-7) M. CONCLUSIONS:
      Sevoflurane was a vasodilator in the feto-placental vasculature in this in vitro
      model. Sevoflurane-mediated vasodilation is NO and cyclooxygenase-independent and
      appears to be mediated in part via a lipoxygenase generated vasodilator
      eicosanoid.

PMID- 18635486
TI  - The status of women in academic anesthesiology: a progress report.
AB  - BACKGROUND: The number of women in medicine has increased steadily in the last
      half century. In this study, we reassessed the status of women in academic
      anesthesiology departments in the United States in 2006. METHODS: Medical
      student, resident, and faculty rank gender data were obtained from the
      Association of American Medical Colleges. Data regarding the make-up and gender
      of anesthesia subspecialty society leadership, the editorial boards of Anesthesia
      & Analgesia and Anesthesiology, the awardees of anesthesia research grants,
      American Board of Anesthesiology examiners, and department chairs were obtained
      from websites, organization management personnel, and the Wood Library-Museum of
      Anesthesiology. Anesthesiology data were compared with composite data from
      medical school departments in other clinical specialties and to data from
      previous years, beginning in 1985. RESULTS: The percentage of medical school
      graduates, anesthesiology residents, and anesthesiology faculty members who are
      women has increased since 1985; however, the rate of increase in the percentage
      of women is significantly faster for medical school graduates compared with
      anesthesiology residents (P < 0.001) and faculty (P < 0.05). The percentage of
      women anesthesiology faculty members who were full professors in 2006 was 6.5%
      compared with 17.7% of men faculty (P < 0.001) and is not significantly different
      than in 1986 (P = 0.27). Fourteen percent of full anesthesiology professors were
      women and this does not differ from all clinical specialties combined (15%).
      Women comprised 12.7% of academic anesthesiology chairs and 10% of all medical
      school department chairs in 2006, significantly higher compared with 1993 (P <
      0.05). Currently, 8% and 11% of editors and associate editors of Anesthesiology
      and Anesthesia & Analgesia are women, respectively. Eighteen percent of American
      Board of Anesthesiology oral board examiners in 2007 were women compared with 8%
      in 1985 (P < 0.05). The percentage of time in which women have served as
      anesthesiology society leaders was significantly greater during 1997-2006
      compared with 1987-1996 (P < 0.001). The proportion of competitive research
      grants awarded to women has not changed over several decades. CONCLUSIONS: The
      status of women in academic anesthesiology in the first decade of the millennium
      has, by some measures, advanced compared with 20 yr ago. However, by other
      measures, there has been no change. The task ahead is to identify factors that
      discourage qualified women medical students, residents, and junior faculty
      members from pursuing careers in academic anesthesiology and advancing in
      academic rank.

PMID- 18635487
TI  - The use of an anesthesia information system to identify and trend gender
      disparities in outpatient medical management of patients with coronary artery
      disease.
AB  - BACKGROUND: Previous anesthesia information management systems-based studies have
      focused on intraoperative data analysis. Reviewing preoperative data could
      provide insight into the outpatient treatment of patients presenting for surgical
      procedures. As gender-based disparities have been demonstrated in the treatment
      of patients with cardiac disease, we hypothesized that there would be gender
      disparities in the outpatient pharmacologic management of patients with coronary
      artery disease (CAD) scheduled for elective noncardiac surgery. METHODS: We
      analyzed electronic medical records of ambulatory patients with CAD (prior
      myocardial infarction [MI], coronary artery bypass surgery, and angioplasty with
      or without stenting, angina) presenting for elective noncardiac surgery between
      1/2004 and 6/2006 (30 mo) at an inner city hospital. RESULTS: Of 21,039
      ambulatory patients seen in the preanesthesia clinic, 6.4% (1346) had CAD.
      Patients with CAD: Men were more likely to be taking beta-blockers (P < 0.002),
      statins (P < 0.0001), aspirin (P < 0.0001), and antiplatelet medications (P <
      0.04), although there was a trend of increased use of aspirin (P < 0.01) by women
      over the course of the study. Patients with history of prior MI: Men with a prior
      MI were more likely to be taking beta-blockers (P < 0.0001) and statins (P <
      0.02), although there was a trend of increased use of beta-blockers (P < 0.0005)
      and aspirin (P < 0.03) by women over the course of the study. Quarterly
      prevalence rates for outpatient medication use were greatest for beta-blockers
      and least for aspirin. Patients were more likely to be taking a statin, aspirin,
      or oral antiplatelet medication if they were receiving chronic beta-blocker
      therapy (P < 0.0001 for each medication). CONCLUSION: Aggregating anesthesia
      management information systems data provides an epidemiological perspective of
      community care of patients presenting for surgery. We found that gender
      disparities in outpatient medical treatment of patients with CAD, which
      previously favored men, have diminished primarily as a result of increased use of
      these medications in women. Nonetheless, despite evidence supporting the use of
      risk-reduction strategies, our patients are undertreated with standard medical
      therapies.

PMID- 18635488
TI  - Neuroanesthesia for the pregnant woman.
AB  - Neuroanesthesia for the pregnant patient is required infrequently, and evidence
      based recommendations for neuroanesthetic management are sparse. We present a
      framework for a practical approach to anesthesia of the pregnant patient with
      subarachnoid or intracerebral hemorrhage, intracranial tumor, traumatic brain
      injury, spinal tumor, or spinal injury. The importance of a team-approach is
      emphasized. The anesthesiologist may have to anesthetize the pregnant patient for
      neurosurgery well before delivery, for cesarean delivery at the time of the
      neurosurgical procedure, or for delivery after neurosurgery. These scenarios are
      discussed along with fetal safety and anesthetic considerations for
      interventional neuroradiology.

PMID- 18635490
TI  - The application of tetanic stimulation of the unilateral tibial nerve before
      transcranial stimulation can augment the amplitudes of myogenic motor-evoked
      potentials from the muscles in the bilateral upper and lower limbs.
AB  - BACKGROUND: Recently, we reported a new technique to augment motor-evoked
      potentials (MEPs) under general anesthesia, posttetanic MEP (p-MEP), in which
      tetanic stimulation of the peripheral nerve before transcranial stimulation
      enlarged amplitudes of MEPs from the muscle innervated by the nerve subjected to
      tetanic stimulation. In the present study, we tested whether tetanic stimulation
      of the left tibial nerve can also augment amplitudes of MEPs from the muscles
      which are not innervated by the nerve subjected to tetanic stimulation. METHODS:
      Thirty patients undergoing spinal surgery under propofol-fentanyl anesthesia with
      partial neuromuscular blockade were examined. For conventional MEP (c-MEP)
      recording, transcranial stimulation with train-of-five pulses was delivered to C3
      4, and the compound muscle action potentials were bilaterally recorded from the
      abductor pollicis brevis, abductor hallucis (AH), tibialis anterior, and soleus
      muscles. For p-MEP recording, tetanic stimulation (50 Hz, 50 mA of stimulus
      intensity) with a duration of 5 s was applied to the left tibial nerve at the
      ankle 1 s before transcranial stimulation. Transcranial stimulation and recording
      of compound muscle action potentials were performed in the same manner as c-MEP
      recording. Amplitudes of c-MEP and p-MEP were compared using Wilcoxon's signed
      rank test. RESULTS: Amplitudes of p-MEPs from the left AH muscle innervated by
      the left tibial nerve with tetanic stimulation were significantly larger compared
      with those of c-MEPs. Amplitudes of p-MEPs from the bilateral abductor pollicis
      brevis and soleus muscles and right AH and tibialis anterior muscles, which were
      not innervated by the left tibial nerve with tetanic stimulation, were also
      significantly larger compared with those of c-MEPs. CONCLUSION: In patients under
      propofol and fentanyl anesthesia with partial neuromuscular blockade, the
      application of tetanic stimulation to the left tibial nerve augmented the
      amplitudes of MEPs from the muscles without tetanic nerve stimulation and those
      with stimulation.

PMID- 18635491
TI  - Cerebral microemboli during hip fracture fixation: a prospective study.
AB  - BACKGROUND: Recent studies have shown that cerebral fat microembolism takes place
      during surgery for hip or knee replacement. In this study, we examined the
      occurrence of cerebral microembolism, solid or gas, during a standard procedure
      of hip fracture fixation. METHODS: This was a prospective study of patients who
      underwent urgent surgery with a dynamic hip screw for hip fracture fixation.
      During surgery, patients were monitored with transcranial Doppler for detection
      of microemboli from right and left middle cerebral arteries. RESULTS: Twenty-two
      patients were included in the study; their median age was 82 yr (range, 51-97
      yr). In nine (41%) patients, high intensity transient signals were recorded,
      indicating microemboli passage in the middle cerebral arteries. All nine patients
      had signals of both solid and gas emboli. One of these nine patients had a
      postoperative cerebrovascular accident. CONCLUSIONS: The incidence of cerebral
      microemboli during urgent surgery for hip fracture fixation is considerable. This
      phenomenon is not confined to hip or knee replacement surgery. The clinical
      implications of this finding require further investigation.

PMID- 18635492
TI  - Pseudomeningocele: an unusual cause of intraoperative tracheal compression and
      expiratory obstruction.
AB  - Cerebrospinal fluid leak resulting from spine surgery has been associated with
      postoperative upper airway obstruction and the need for emergent airway
      management. We report a case of a known pseudomeningocele resulting in acute
      intraoperative compression of the intrathoracic trachea and an unexpected
      variable expiratory obstruction.

PMID- 18635493
TI  - Status epilepticus and intrathecal fluorescein: anesthesia providers beware.
AB  - Fluorescein is a fluorochrome dye occasionally administered by intrathecal
      injection to identify and localize cerebrospinal fluid leaks. Although generally
      considered to be a benign intervention, intrathecal administration of fluorescein
      has resulted in adverse events. We report a case of status epilepticus after
      intrathecal administration of fluorescein. Anesthesia providers should be aware
      of complications associated with intrathecal fluorescein use and be prepared to
      manage neurologic complications during the perioperative period.

PMID- 18635489
TI  - Gender and the injured brain.
AB  - Anesthesiologists are frequently confronted with patients who are at risk for
      neurological complications due to perioperative stroke or prior traumatic brain
      injury. In this review, we address the growing and fascinating body of data that
      suggests gender and sex steroids influence the pathophysiology of injury and
      outcome for these patients. Cerebral ischemia, traumatic brain injury, and
      epilepsy are reviewed in the context of potential sex differences in mechanisms
      and outcomes of brain injury and the role of estrogen, progesterone, and
      androgens in shaping these processes. Lastly, implications for current and future
      perioperative and intensive care are identified.

PMID- 18635494
TI  - Gender issues in transplantation.
AB  - The effects of gender mismatch in clinical transplantation have been recognized
      for half a century. But gender issues in clinical transplantation affect outcomes
      at many levels beyond immunologic concerns. Many diseases leading to
      transplantation are predominantly expressed in one gender. Organ donation
      patterns have consistently been defined by a greater tendency of women to be live
      donors. Access to transplantation may be affected by subtleties in the
      interactions of transplant personnel with women versus men candidates. In the new
      field of stem-cell transplantation, functional differences in male versus female
      adult stem cells may shed light on gender differences in outcomes for solid organ
      transplantation. This review highlights gender issues related to transplantation
      with a goal of optimizing the care of all transplant patients.

PMID- 18635495
TI  - Renal ischemia: does sex matter?
AB  - Renal ischemia is a common complication in the perioperative period that leads to
      a high rate of morbidity and mortality. As in other forms of ischemia (i.e.,
      cardiac, neurologic), the incidence and outcome of renal ischemia is strikingly
      sex-specific. Sexual dimorphism in response to renal injury has been noted for
      many years, but is now the subject of both clinical and experimental research.
      Clinically, women experience a lower incidence of perioperative acute renal
      failure, with the exception of cardiac surgery. Experimental science is now
      producing tantalizing clues that sex steroids, both male and female, play a role
      in the kidney's response to ischemia. In this review, we evaluated sex
      differences in perioperative renal failure and in the pathophysiology of renal
      ischemia/reperfusion injury. Although much work remains to characterize the
      biological mechanisms involved, the data are sufficient to support consideration
      of gender and the use of medications that impact steroid availability in the
      perioperative plan of care.

PMID- 18635497
TI  - The effect of different crystalloid solutions on acid-base balance and early
      kidney function after kidney transplantation.
AB  - BACKGROUND: This study aimed to quantify changes in acid-base balance, potassium
      and lactate levels as a function of administration of different crystalloid
      solutions during kidney transplantation, and to determine the ideal fluid for
      such patients. METHODS: In this double-blind study, patients were randomized to
      three groups (n = 30 each) to receive either normal saline, lactated Ringer's, or
      Plasmalyte, all at 20-30 mL x kg(-1) x h(-1). Arterial blood analyses were
      performed before induction of anesthesia, and at 30-min intervals during surgery,
      and total IV fluids recorded. Urine volume, serum creatinine and BUN, and
      creatinine clearance were recorded on postoperative days 1, 2, 3, and 7. RESULTS:
      There was a statistically significant decrease in pH (7.44 +/- 0.50 vs 7.36 +/-
      0.05), base excess (0.4 +/- 3.1 vs -4.3 +/- 2.1), and a significant increase in
      serum chloride (104 +/- 2 vs 125 +/- 3 mM/L) in patients receiving saline during
      surgery. Lactate levels increased significantly in patients who received Ringer's
      lactate (0.48 +/- 0.29 vs 1.95 +/- 0.48). No significant changes in acid-base
      measures or lactate levels occurred in patients who received Plasmalyte.
      Potassium levels were not significantly changed in any group. CONCLUSIONS: All
      three crystalloid solutions can be safely used during uncomplicated, short
      duration renal transplants; however, the best metabolic profile is maintained in
      patients who receive Plasmalyte.

PMID- 18635498
TI  - Vanilloid-induced conduction analgesia: selective, dose-dependent, long-lasting,
      with a low level of potential neurotoxicity.
AB  - Vanilloid agonists (capsaicin, resiniferatoxin, [RTX]) applied to the peripheral
      nerves provide conduction blockade. In contrast to the analgesic component of
      conduction anesthesia produced by local anesthetics, vanilloid agonists provide
      conduction analgesia not associated with suppression of motor or sensory
      functions not related to pain. Vanilloid agonists provide conduction analgesia
      selectively because their effect on the nerve trunks is limited to C- and ADelta
      fibers. RTX is much more potent than capsaicin and has a wider therapeutic
      window. In rat experiments, perineural RTX produced a long-lasting thermal and
      mechanical hypoalgesia with a very wide separation between effective
      concentrations (from 0.00003% to 0.001%) providing an effect lasting from several
      hours to several weeks. A nerve block with RTX prevented the development of
      thermal and mechanical hyperalgesia as well as pain behavior in a model of
      incisional pain. RTX-induced conduction blockade has an inherent drawback of
      TRPV1 agonists, the initial excitation (pain); therefore, a local anesthetic
      should be injected to prevent it. When RTX was applied to the rat's sciatic nerve
      in doses necessary to provide conduction analgesia, the frequency of unmyelinated
      fiber degeneration was more than an order of magnitude lower than that with the
      therapeutic concentration of lidocaine. These promising results should be
      confirmed by experiments in species other than rodents (pigs, sheep). Taken
      together, the data indicate possible clinical applicability of vanilloid-induced
      conduction analgesia.

PMID- 18635499
TI  - The effect of wound instillation of a novel purified capsaicin formulation on
      postherniotomy pain: a double-blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Acute postoperative pain is common after most surgical procedures.
      Despite the availability of many analgesic options, postoperative pain management
      is often unsatisfactory. Purified capsaicin (ALGRX 4975 98% pure) has
      demonstrated prolong inhibition of C-fiber function in in vitro, preclinical, and
      clinical studies, and may be an effective adjunct to postoperative pain
      management. METHODS: We performed a single-center, randomized, double-blind,
      placebo-controlled study of the analgesic efficacy of a single intraoperative
      wound instillation of 1000 microg ultrapurified capsaicin (ALGRX 4975) after open
      mesh groin hernia repair in 41 adult male patients. The primary end-point was
      average daily visual analog scale (VAS) pain scores during the first week after
      surgery assessed as area under the curve (AUC). Pain was recorded twice daily in
      a pain diary for 4 wk. Physical examination and laboratory tests were done before
      and 1 wk after surgery, together with recordings of adverse events up to 28 days.
      Adverse events were recorded. Data were also analyzed using a mixed-effects
      analysis with NONMEM. RESULTS: VAS AUC was significantly lower during the first 3
      days postoperatively (P < 0.05), but not for the whole 1 or 4 wk postoperatively.
      Mixed-effects analysis with NONMEM revealed that pain scores were significantly
      lower (P < 0.05) in the capsaicin group during the first 4 days. No clinically
      significant serious adverse events were observed, although a mild transient
      increase in liver enzymes was seen more often in the capsaicin-treated group.
      CONCLUSION: In the setting of a well-defined analgesic protocol standard, VAS AUC
      analysis and a mixed-effect analysis showed superior analgesia of capsaicin
      relative to placebo during the first 3-4 days after inguinal hernia repair.

PMID- 18635500
TI  - Intraarticular tramadol-bupivacaine combination prolongs the duration of
      postoperative analgesia after outpatient arthroscopic knee surgery.
AB  - BACKGROUND: Intraarticular (IA) local anesthetics are often used for the
      management and prevention of pain after arthroscopic knee surgery. Recently, IA
      tramadol was also used for the management of these patients. However, the IA
      combination of local anesthetic and tramadol has not been evaluated in
      arthroscopic outpatients. Our primary aim in this study was to evaluate the
      analgesic effect of an IA combination of bupivacaine and tramadol when compared
      with each drug alone using visual analog scale (VAS) pain scores in patients
      undergoing day-care arthroscopic knee surgery. Additionally, we assessed
      analgesic demand. METHODS: Ninety ASA I/II patients undergoing arthroscopic
      partial meniscectomy, performed by a single surgeon under general anesthesia,
      were assigned in a randomized, double-blind manner into three groups: group B (n
      = 30) received 0.25% bupivacaine, group T (n = 30) received 100 mg tramadol, and
      group BT (n = 30) received 0.25% bupivacaine and 100 mg tramadol to a total
      volume of 20 mL by the IA route after surgery. Postoperative pain scores were
      measured on a VAS, at rest and on mobilization at 0.5, 1, 2, 4, 6, 8, 12, and 24
      h. Duration of analgesia, the subsequent 24 h consumption of rescue analgesia,
      time to ambulation, and time to discharge were evaluated. In addition, the
      systemic side effects of the IA injected drugs were also assessed. RESULTS: The
      results showed significantly lower VAS pain scores in group BT (P << 0.1) when
      compared with groups T and B. Group BT had a later onset of postsurgical pain and
      longer time to first rescue analgesic than groups B and T. The 24 h consumption
      of analgesic was significantly less in group BT when compared with the other two
      groups (26.7% of the patients required rescue analgesia in group BT, whereas this
      number was 90% in group B and 86.7% in group T). In addition, time in hours to
      discharge and time to unassisted ambulation were significantly shorter in group
      BT when compared with groups T and B, and this was not associated with any
      detectable systemic effects. CONCLUSION: The IA admixture of tramadol 100 mg with
      bupivacaine 0.25% provides a pronounced prolongation of analgesia compared with
      either drug alone in patients undergoing day care arthroscopic knee surgery.

PMID- 18635501
TI  - A new knee surgery model in rats to evaluate functional measures of postoperative
      pain.
AB  - INTRODUCTION: With the increase in the number of total knee surgeries being
      performed, postoperative analgesic management remains a challenge. We used a new
      animal knee surgery model to characterize pain-related behavior in the rat, and
      its therapeutic modulation with systemic and intrathecal drug treatment. METHODS:
      Rats were anesthetized with isoflurane and an incision was made over the left
      knee to expose the patella tendon. The tendon was reflected aside and a 1.4-mm
      diameter, 0.5 mm deep hole was drilled in both the femur and tibia at 2 mm above
      and below the knee joint, respectively. The holes were filled with dental cement
      and the wound was closed. Sham surgery animals only had a skin incision. Some
      animals had previously been implanted with a lumbar intrathecal catheter for drug
      injection. At 24 h after surgery, animals received the following drugs
      systemically: i.p. morphine sulfate 0.3-1 mg/kg, i.p. ketorolac 2.5-20 mg/kg,
      p.o. celecoxib 10-50 mg/kg, i.p. ketamine hydrochloride 2.5-10 mg/kg, i.p.
      clonidine hydrochloride 25 microg/kg, p.o. pregabablin 10-20 mg/kg, or drug
      vehicle; or intrathecally: morphine sulfate 0.3-1 microg, ketorolac 4-80 microg,
      L-745,337 80 microg, pregabalin 15 microg, neostigmine 0.5 microg, or saline
      vehicle. Pain-related behavior was then assessed by recording exploratory
      spontaneous activity, in which vertical and horizontal light beam interruptions
      were automatically recorded to measure rearing activity and ambulation for 60
      min. Data were compared using analysis of variance with the Tukey-B post hoc
      test. RESULTS: The model demonstrated deficits in rearing and ambulation compared
      with sham skin incision control animals on postsurgery days 1-3. Systemic and
      intrathecal morphine improved rearing and ambulation, with knee surgery/ morphine
      rats displaying as much activity as sham skin incision/vehicle animals, whereas
      knee surgery/vehicle rats showed decreased activity. Systemic ketorolac 20 mg/kg
      improved rearing and ambulation, with knee surgery/ketorolac rats showing
      increased activity compared with knee surgery/vehicle animals. Intrathecal
      ketorolac 4-40 microg did not increase rearing or ambulation, but the 80 microg
      dose was effective. Other drugs tested, systemically or intrathecally, did not
      restore activity to normal levels. CONCLUSION: This study presents a new simple,
      reproducible rat model to assess function and discomfort after knee surgery, and
      one that responds to therapeutic interventions. In this knee surgery model, both
      systemic and intrathecal administration of either morphine or ketorolac caused
      reversal of the deficits in rearing and ambulatory behavior at 24 h postsurgery.

PMID- 18635503
TI  - A high concentration of resiniferatoxin inhibits ion channel function in clonal
      neuroendocrine cells.
AB  - BACKGROUND: Resiniferatoxin (RTX) is a potent agonist of the transient receptor
      potential vanilloid 1 channel (TRPV1) found in peripheral nociceptors. RTX causes
      cellular excitation first, followed by a long-lasting refractory state, which has
      suggested its therapeutic use for pain control. RTX's effect could result from
      specific actions on TRPV1 channels, but might also arise from previously reported
      TRPV1-independent effects. We have tested whether exposure to RTX compromises ion
      channels in a TRPV1-independent manner. METHODS: Clonal rat anterior pituitary
      (GH(3)) cells, loaded with the Ca(+2)-sensitive fluorescent dye (fluo-4), were
      stimulated with the Na(+) channel activator veratridine (VTD) or directly
      depolarized by 60 mM K(+) solution. The physiological effects of exposure to RTX
      were evaluated by stimulated increases of fluorescence from raised intracellular
      [Ca(2+)]. RESULTS: The presence of 10 microM RTX acutely reduced the median
      fluorescence changes by VTD and 60 mM K(+) to 45% and 50%, respectively (P =
      0.018 and 0.043). Prolonged exposure (24 h) of cells to 10 microM RTX, followed
      by a 2 h washout, reduced the median fluorescence changes by VTD and 60 mM K(+)
      to 5.6% and 42% of control changes, respectively (P = 0.027 and 0.011). Cell
      responses to VTD partially recovered, to 42% of control, after incubation in RTX
      free medium for 24 h. CONCLUSION: RTX at 10 microM directly and acutely inhibited
      voltage-dependent Ca(2+) channels, in a TRPV1-independent manner. Prolonged
      exposure (24 h) to 10 microM RTX inhibited voltage-dependent Na(+) channels in
      addition to the Ca(2+) channels, in at least a partially reversible manner.

PMID- 18635504
TI  - Long-term survival after colon cancer surgery: a variation associated with choice
      of anesthesia.
AB  - BACKGROUND: A previously published clinical trial of epidural-supplemented versus
      general anesthesia, Veterans Affairs Cooperative Study No. 345, showed no
      difference in 30-day mortality and morbidity rates between the two treatments. We
      hypothesized that long-term postoperative survival would be increased by epidural
      anesthesia/analgesia supplementation during colon cancer resection. METHODS: We
      studied long-term survival after resection of colon cancer in a trial of general
      anesthesia with and without epidural anesthesia and analgesia supplementation for
      resection of colon cancer in Veterans Affairs Cooperative Study No. 345. Cox and
      log-normal survival models were used to test the effects of pathological stage,
      type of anesthesia and other covariates on survival in 177 patients. RESULTS: The
      presence of distant metastases had the greatest effect on survival. Thus,
      analyses were performed separately for patients with and without metastases. For
      those without metastasis, the hazard ratio for the treatment effects changed at
      1.46 years. Before 1.46 years, epidural supplementation was associated with
      improved survival (P = 0.012), while later, the type of anesthesia did not appear
      to affect survival (P = 0.27). Hypertension was associated with poorer survival
      (P = 0.029), as was alcoholism in patients who received epidural anesthesia (P =
      0.014). Survival of patients with metastases was unaffected by type of
      anesthesia. There was a significant age by hypertension interaction (P = 0.002).
      Patients survived longer if they were hypertensive, but had reduced survival if
      they were older than 66 years and hypertensive. CONCLUSION: Epidural
      supplementation was associated with enhanced survival among patients without
      metastases before 1.46 years. Epidural anesthesia had no effect on survival of
      patients with metastases. Additional studies to confirm or refute these findings
      are warranted.

PMID- 18635502
TI  - Sex, gender, and pain: an overview of a complex field.
AB  - Traditionally, biomedical research in the field of pain has been conducted with
      male animals and subjects. Over the past 20-30 yr, it has been increasingly
      recognized that this narrow approach has missed an important variable: sex. An
      ever-increasing number of studies have established sex differences in response to
      pain and analgesics. These studies have demonstrated that the differences between
      the sexes appear to have a biological and psychological basis. We will provide
      brief review of the epidemiology, rodent, and human experimental findings. The
      controversies and widespread disagreement in the literature highlight the need
      for a progressive approach to the questions involving collaborative efforts
      between those trained in the basic and clinical biomedical sciences and those in
      the epidemiological and social sciences. In order for patients suffering from
      acute and/or chronic pain to benefit from this work, the approach has to involve
      the use or development of clinically relevant models of nociception or pain to
      answer the basic, but complex, question. The present state of the literature
      allows no translation of the work to our clinical decision-making.

PMID- 18635505
TI  - Epidural volume extension and intrathecal dose requirement: plain versus
      hyperbaric bupivacaine.
AB  - BACKGROUND: Epidural volume extension leads to an increase in sensory spread of
      local anesthetic, but whether this translates into lower dose requirements during
      combined spinal epidural (CSE) remains undetermined. Likewise, the influence of
      intrathecal drug baricity on the dose-sparing effect of epidural volume extension
      has not been investigated. We studied the dose-sparing effect of epidural volume
      extension and its relation to intrathecal drug baricity by comparing the ED(50)
      of plain and hyperbaric bupivacaine with and without epidural volume extension.
      METHODS: Eighty-eight adult male patients scheduled for lower limb orthopedic
      surgery under CSE in the sitting position were randomized to four groups (n = 22
      each); intrathecal injection was made with plain bupivacaine in groups plain
      bupivacaine (PB) and plain bupivacaine with epidural volume extension (PBE), and
      hyperbaric bupivacaine in groups hyperbaric bupivacaine (HB) and hyperbaric
      bupivacaine with epidural volume extension (HBE). Fentanyl, 25 microg, was added
      to the intrathecal drug in all groups. Among these four groups, epidural volume
      extension was performed with 10 mL normal saline only for groups PBE and HBE. The
      dose of spinal bupivacaine was varied using the up-and-down sequential allocation
      method. The first patient of each group received 10 mg bupivacaine. A successful
      spinal block was defined as attainment of sensory level of at least T10 along
      with complete motor blockade within 20 min of the intrathecal injection. The dose
      of bupivacaine was sequentially increased or decreased by 1 mg depending on
      whether spinal block was a failure or success in the previous patient. RESULTS:
      The addition of epidural volume extension to plain bupivacaine, i.e., group PBE
      versus group PB, resulted in a significant decrease in ED(50) (relative potency
      estimate: 1.2, 95% CI: 1.04-1.64) and increase in maximum sensory level (T6 vs
      T8, respectively, P < 0.05). These differences were not seen with hyperbaric
      bupivacaine (group HB vs HBE). Independent of the effect of epidural volume
      extension, the ED(50) of plain bupivacaine when compared with hyperbaric
      bupivacaine was significantly lower (relative potency estimate of group PB vs
      group HB: 0.78, 95% CI: 0.54-0.93; and for group PBE vs group HBE: 0.68, 95% CI:
      0.37-0.87). CONCLUSIONS: Administered with or without epidural volume extension,
      plain bupivacaine appears to be more effective, requiring a smaller dose and
      producing a higher sensory block with an earlier onset in comparison to
      hyperbaric bupivacaine. Epidural volume extension, when applied to intrathecal
      hyperbaric bupivacaine, fails to decrease the dose or raise the level of block.

PMID- 18635506
TI  - Intercostally placed paravertebral catheterization: an alternative approach to
      continuous paravertebral blockade.
AB  - BACKGROUND: Continuous paravertebral nerve blocks can provide effective
      postoperative analgesia after abdominal and thoracic surgery. While offering a
      number of advantages compared with thoracic epidural analgesia, access to the
      paravertebral space using a classic approach is not always easily accomplished
      and/or possible. In this regard, continuous paravertebral blockade via a
      percutaneous intercostal approach may theoretically serve as an alternative
      approach to the paravertebral space. METHODS: One hundred ten patients undergoing
      major abdominal, thoracic, or retroperitoneal procedures had preoperative
      placement of unilateral or bilateral paravertebral catheter(s) via an intercostal
      approach. At a point 8 cm lateral to the midline a 5 cm, 18 G Tuohy needle was
      advanced with the needle tip angled 45 degrees cephalad and 60 degrees medial to
      the sagittal plane to come in contact with the lower third of the rib. The needle
      was "walked-off" the inferior border of the rib while maintaining its orientation
      and advanced a further 5 to 6 mm under the rib to lie in the subcostal groove.
      After injection of 5 mL ropivacaine 0.5%, a catheter was advanced medially the
      estimated distance to the paravertebral space. Postoperatively 0.2% ropivacaine
      was continuously infused at 10 mL/h in each catheter with hourly boluses of 5 mL
      available for breakthrough pain. RESULTS: Median pain scores averaged 2 on a
      scale of 0-10 and patient-controlled analgesia hydromorphone consumption averaged
      only 1.69 mg for the first 24 h postoperatively. There were no clinically
      significant complications of the technique. CONCLUSION: The intercostally placed
      paravertebral catheter provides postoperative analgesia after major surgery of
      the chest, abdomen, or retroperitoneum.

PMID- 18635507
TI  - What is the best choice for size of double lumen tube?

PMID- 18635508
TI  - Undersizing left double-lumen tubes.

PMID- 18635509
TI  - Etomidate, nitric oxide, and cerebral vasospasm.

PMID- 18635510
TI  - Esophageal seal is not the only consideration in supraglottic airway devices.

PMID- 18635511
TI  - Smoking and nalbuphine may reduce postoperative emesis.

PMID- 18635512
TI  - Airtraq as an intubating conduit.

PMID- 18635513
TI  - Esophageal Doppler monitor: a new tool in monitoring video assisted thoracoscopic
      surgery for ligation of patent ductus arteriosus.

PMID- 18635514
TI  - Mirtazapine relieves postdural puncture headache.

PMID- 18635515
TI  - Unexpected internal jugular vein obstruction revealed by ultrasound surface scan
      before central venous catheter insertion.

PMID- 18635516
TI  - Transesophageal Doppler probe and proseal laryngeal mask airway. A new technique
      for probe insertion in pediatric anesthesia.

PMID- 18635517
TI  - Safety of contrast-enhanced echocardiography within 24 h after acute myocardial
      infarction.
AB  - AIMS: Contrast-enhanced echocardiography is widely used to enhance left
      ventricular (LV) endocardial border delineation in stable patients with known or
      suspected coronary artery disease. In patients with acute myocardial infarction,
      accurate assessment of LV function and size is important, but data on the safety
      of contrast-enhanced echocardiography in the early stage of myocardial infarction
      (within 24 h) are lacking. In the current study, the experience on the safety of
      contrast-enhanced echocardiography within 24 h of acute myocardial infarction is
      reported. METHODS AND RESULTS: A total of 115 consecutive patients (58 +/- 11
      years; 77% male) admitted to the coronary care unit for ST-elevation acute
      myocardial infarction underwent clinically indicated contrast-enhanced
      echocardiography within 24 h of hospital admission to assess LV size and
      function. Perflutren (Luminity, Bristol-Myers Squibb Pharma, Bruxelles, Belgium)
      was used as contrast agent. Safety was determined evaluating vital signs,
      physical examination, ECG, and adverse events. On contrast-enhanced
      echocardiography, the mean LV ejection fraction was 44 +/- 11%, and 56% of
      patients had an LV ejection fraction </=45%. Administration of echo contrast did
      not induce any significant change in vital signs, physical examination, and ECG.
      Major adverse events were not observed whereas minor events occurred in 4% of
      patients (hypersensitivity at the injection site in three and transient back pain
      in two). CONCLUSION: These data provide evidence on the safety of contrast
      enhanced echocardiography in the first 24 h of myocardial infarction; larger
      patient cohorts are needed to confirm these findings.

PMID- 18635518
TI  - Baffle puncture guided by transoesophageal echocardiography in a patient with
      dextrocardia and Mustard correction.
AB  - A baffle puncture is a challenging procedure but can be safely done using direct
      visualization of the region of interest. To our knowledge, however, it has never
      been performed in a patient with dextrocardia. We present a 62-year-old male with
      dextrocardia, right isomerism, congenitally corrected transposition of the great
      arteries, persistent left-sided superior and inferior caval veins, atrial septum
      defect, and pulmonary valve stenosis. The atrial septum defect was surgically
      closed with a Teflon patch, a variant Mustard operation was performed, and also a
      prosthetic tricuspid valve was implanted. The patient developed multiple episodes
      of atrial tachycardia leading to acute heart failure on many occasions. An
      electrophysiological study was undertaken in order to create a bi-atrial electro
      anatomical map. Owing to the presence of a prosthetic tricuspid valve, the
      femoral venous access was used and a baffle puncture was performed using
      continuous monitoring with fluoroscopy and transoesophageal echocardiography
      (TEE). The baffle puncture was successful and the tachycardia was ablated in the
      systemic venous atrium. To our knowledge, we present the very first case report
      demonstrating a successful baffle puncture in a patient with dextrocardia and
      Mustard correction. Direct imaging using TEE seems to be a very useful tool for
      guiding the puncture.

PMID- 18635519
TI  - Prediction models to identify hospitalized patients at risk of being colonized or
      infected with multidrug-resistant Acinetobacter baumannii calcoaceticus complex.
AB  - BACKGROUND: The multidrug-resistant (MDR) Acinetobacter baumannii calcoaceticus
      complex (Abc) has emerged as an important cause of nosocomial infections. The
      aims of the study were to evaluate risk factors for MDR-Abc in intensive care
      units (ICUs) as well as in medical and surgical wards, to define the likelihood
      ratios (LRs) of risk factors and to determine if risk factors differ depending on
      whether colonization or infections are considered. METHODS: Two prospective
      matched case-control studies were performed. MDR-Abc was defined as a strain
      resistant to four or more classes of antibiotics. The two case groups included
      patients with MDR-Abc infections or colonization. Controls were selected among
      patients not harbouring Abc. Matching criteria were the number of days from
      admission to MDR-Abc isolation among cases and the duration of hospitalization
      among controls. RESULTS: Overall, 514 patients were included in the study. One
      hundred and thirty-seven patients were infected and 120 colonized. A Charlson
      score >3 and previous methicillin-resistant Staphylococcus aureus isolation and
      beta-lactam use were independent risk factors for colonization and infection.
      Bedridden status and previous ICU admission were associated with colonization,
      while the presence of a central venous catheter and surgery were related to
      infection. The analysis of LRs showed an association between the presence of more
      than two risk factors and colonization or infection. The highest predicting value
      was observed for the presence of more than two risk factors and colonization in
      patients with no history of ICU admission. CONCLUSIONS: This study provides novel
      information that can be used to identify interventions for different stages of
      the spread of MDR-Abc.

PMID- 18635520
TI  - Telavancin and vancomycin pharmacodynamics with Staphylococcus aureus in an in
      vitro dynamic model.
AB  - OBJECTIVES: The aim of this study was to compare the pharmacodynamics of
      telavancin (TLV) and vancomycin (VAN) with Staphylococcus aureus. Their
      concentrations were simulated between the MIC and the mutant prevention
      concentration (MPC), and above the MPC. METHODS: Two strains of S. aureus,
      glycopeptide-intermediate S. aureus (GISA) Mu-50 and ATCC 43300, were exposed for
      5 days to once-daily TLV (half-life 8 h) and twice-daily VAN (half-life 6 h). The
      simulated ratios of 24 h area under the curve (AUC(24)) to MIC varied from 30-50
      to 3400 h. The cumulative antimicrobial effect was expressed by ABBC (area
      between the level corresponding to the starting inoculum and the time-kill curve
      calculated from time 0 to 144 h). RESULTS: With each antibiotic, the ABBC versus
      log AUC(24)/MIC relationships were bacterial strain-independent. A sigmoid model
      fits combined data on both organisms exposed to TLV (r(2)=0.78) or VAN
      (r(2)=0.85). Comparable effects of the proposed therapeutic dose of TLV (10
      mg/kg) and a clinical dose of VAN (2x1 g) were predicted for MRSA ATCC 43300
      (AUC(24)/MIC 3400 and 500 h, respectively) and a 1.6-fold greater effect of TLV
      for GISA Mu-50 compared with VAN (AUC(24)/MIC 1700 and 130 h, respectively).
      Mutants of S. aureus ATCC 43300 resistant to 2x and 4x MIC of VAN but not TLV
      were enriched in these simulations. No selection of TLV- and VAN-resistant
      mutants of GISA Mu-50 was observed. CONCLUSIONS: These in vitro data suggest that
      the effects of clinically attainable AUC/MIC ratios of TLV are similar to those
      of VAN on S. aureus 43300 and 2-fold greater on GISA Mu-50.

PMID- 18635521
TI  - Alexidine and chlorhexidine bind to lipopolysaccharide and lipoteichoic acid and
      prevent cell activation by antibiotics.
AB  - OBJECTIVES: Many antibiotics used to treat infections cause release of
      immunostimulatory cell wall components from bacteria. Therefore, a combination of
      antimicrobial and endotoxin-neutralizing activity is desired to prevent
      inflammation induced by destroyed bacteria. Chlorhexidine and alexidine are
      amphipathic bisbiguanides and could neutralize bacterial membrane components as
      stimulators of Toll-like receptors (TLRs). METHODS: Binding of chlorhexidine and
      alexidine to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) was determined
      by fluorescence displacement assay and isothermal calorimetric titration.
      Neutralization of the biological effect of LPS and LTA on TLR-activated cellular
      activation was determined by NF-kappaB reporter luciferase activation on cells
      transfected with specific TLRs and NO production of murine macrophages in the
      presence of isolated agonists and antibiotic-treated bacteria. RESULTS: Alexidine
      and chlorhexidine bind not only to LPS but also to LTA from Gram-positive
      bacteria. Alexidine has a higher affinity than chlorhexidine for both compounds.
      Calorimetric titration shows an initial endothermic contribution indicating
      participation of hydrophobic interactions in LPS binding, while binding to LTA
      displayed initial exothermic contribution. Both compounds prevent cell activation
      of TLR4 and TLR2 by LPS and LTA, respectively. The addition of both compounds
      suppressed NO production by macrophages in the presence of bacteria treated with
      different types of antibiotics. CONCLUSIONS: Chlorhexidine and alexidine suppress
      bacterial membrane-induced cell activation at concentrations two orders of
      magnitude lower than that used in topical applications. Combining biocides with
      different types of antibiotics prevented macrophage activation in the presence of
      bacteria and demonstrated the potential of chlorhexidine and alexidine to
      suppress inflammatory responses caused by activation of TLRs.

PMID- 18635522
TI  - CpG methylation in exon 1 of transcription factor 4 increases with age in normal
      gastric mucosa and is associated with gene silencing in intestinal-type gastric
      cancers.
AB  - Transcriptional factor 4 (TCF4), encoding a basic helix-loop-helix
      transcriptional factor, has recently been demonstrated as a causative gene for
      Pitt-Hopkins syndrome, a neurodevelopmental disease. Examination of gastric
      cancers using the restriction landmark genomic scanning technique revealed
      methylation at a NotI enzyme site in TCF4 intron 8 and further identified CpG
      dinucleotide hypermethylation in TCF4 exon 1, strongly associated with gene
      silencing in gastric cancer cell lines. Treatment with 5-aza-2'-deoxycytidine
      and/or trichostatin A restored TCF4 expression in TCF4-silenced gastric cancer
      cell lines. Real-time reverse transcription-polymerase chain reaction analysis of
      77 paired primary gastric tumor samples revealed that 38% of analyzed tumors had
      a >2-fold decrease in TCF4 expression compared with adjacent normal-appearing
      tissue, and the decrease significantly correlated with increased CpG methylation
      in TCF4 exon 1. Clinicopathologic data showed that decreased TCF4 expression
      occurred significantly more frequently in intestinal-type (22/37, 59%) than in
      diffuse-type (7/37, 19%) gastric cancers (P = 0.0004) and likewise more
      frequently in early (12/18, 67%) than in advanced (17/59, 29%) gastric cancers (P
      = 0.004). CpG methylation markedly increased with patient age among normal
      appearing tissues, suggesting that CpG methylation in gastric mucosa may be one
      of the earliest events in carcinogenesis of intestinal-type gastric cancers.
      Furthermore, ectopic expression of TCF4 decreased cell growth in a gastric cancer
      cell line, and the knock down of TCF4 using small interfering RNA increased cell
      migration. Based on these results, we propose that the observed frequent
      epigenetic-mediated TCF4 silencing plays a role in tumor formation and
      progression.

PMID- 18635523
TI  - Genotypes and haplotypes of ERCC1 and ERCC2/XPD genes predict levels of
      benzo[a]pyrene diol epoxide-induced DNA adducts in cultured primary lymphocytes
      from healthy individuals: a genotype-phenotype correlation analysis.
AB  - Benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts are a risk factor for
      tobacco-related cancers. Excision repair cross-complementing complementation
      group 1 (ERCC1) and excision repair cross-complementing complementation group
      2/xeroderma pigmentosum D (ERCC2/XPD) participate in the nucleotide excision
      repair (NER) pathway that removes BPDE-DNA adducts; however, few studies have
      provided population-based evidence for this association. Therefore, we assayed
      for levels of in vitro BPDE-induced DNA adducts and genotypes of single
      nucleotide polymorphisms (SNPs) of the NER genes ERCC1 (rs3212986 and rs11615)
      and ERCC2/XPD (rs13181, rs1799793 and rs238406) in 707 healthy non-Hispanic
      whites. The linear trend test of increased adduct values in never to former to
      current smokers was statistically significant (P(trend) = 0.0107). The median DNA
      adduct levels for the ERCC2 rs1799793 GG, GA and AA genotypes were 23, 29 and 30,
      respectively (P(trend) = 0.057), but this trend was not observed for other SNPs.
      After adjustment for covariates, adduct values larger than the median value were
      significantly associated with the genotypes ERCC1 rs3212986TT [odds ratio (OR) =
      1.89, 95% confidence interval (CI) = 1.03-3.48] and ERCC2/XPD rs238406AA (OR =
      0.64, 95% CI = 0.41-0.99) and rs238406CA (OR = 0.63, 95% CI = 0.45-0.89) compared
      with their corresponding wild-type homozygous genotypes. The results of haplotype
      analysis further suggested that haplotypes CAC and CGA of ERCC2/XPD, TC of ERCC1
      and CACTC of ERCC2/XPD and ERCC1 were significantly associated with high levels
      of DNA adducts compared with their most common haplotypes. Our findings suggest
      that the genotypes and haplotypes of ERCC1 and ERCC2/XPD may have an effect on in
      vitro BPDE-induced DNA adduct levels.

PMID- 18635524
TI  - The sensitivity to beta-carotene growth-inhibitory and proapoptotic effects is
      regulated by caveolin-1 expression in human colon and prostate cancer cells.
AB  - Although several mechanisms have been proposed to explain the putative role of
      beta-carotene in cancer, no studies have investigated a possible influence of
      beta-carotene on caveolin-1 (cav-1) pathway, an important intracellular signaling
      deregulated in cancer. Here, different human colon and prostate cancer cell
      lines, expressing (HCT-116, PC-3 cells) or not (Caco-2, LNCaP cells) cav-1, were
      treated with varying concentrations of beta-carotene (0.5-30 muM) for different
      periods of time (3-72 h) and the effects on cell growth were investigated. The
      results of this study show that (i) beta-carotene acted as a growth-inhibitory
      agent in cav-1-positive cells, but not in cav-1-negative cells; (ii) in cav-1
      positive cells, the carotenoid downregulated in a dose- and time-dependent manner
      the expression of cav-1 protein and messenger RNA levels and inhibited AKT
      phosphorylation which, in turn, stimulated apoptosis by increasing the expression
      of beta-catenin and c-myc and the activity of caspases-3, -7, -8 and -9; when the
      carotenoid was removed from culture medium, a progressive increase in cell growth
      was observed with respect to beta-carotene-treated cells and (iii) the
      transfection of cav-1 in cav-1-negative cells increased cell sensitivity to beta
      carotene by inducing apoptosis. This effect was accompanied by a reduction of
      both cav-1 and AKT phosphorylation and by an increase of c-myc and beta-catenin
      expression. Silencing of c-Myc attenuated beta-carotene-induced apoptosis and
      beta-catenin expression. All together, these data suggest that the modulation of
      cav-1 pathway by beta-carotene could be a novel mechanism by which the carotenoid
      acts as a potent growth-inhibitory agent in cancer cells.

PMID- 18635525
TI  - Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born
      to mothers administered green tea: primary role of caffeine.
AB  - Our laboratory recently developed a mouse model of transplacental induction of
      lymphoma, lung and liver cancer by the polycyclic aromatic hydrocarbon,
      dibenzo[a,l]pyrene (DBP). Pregnant B6129SF1 females, bred to 129S1/SvIm males,
      were treated on day 17 of gestation with an oral dose of 15 mg/kg DBP. Beginning
      on day 0 of gestation, dams were given (ad lib) buffered water, 0.5% green tea,
      0.5% decaffeinated green tea, caffeine or epigallocatechin-3-gallate (EGCG) (both
      at equivalent concentrations found in tea). The concentration of the teas (and
      corresponding caffeine and EGCG) was increased to 1.0% upon entering the second
      trimester, 1.5% at onset of the third trimester and continued at 1.5% until pups
      were weaned at 21 days of age. Offspring were raised with normal drinking water
      and AIN93G diet. Beginning at 2 months of age, offspring experienced significant
      mortalities due to an aggressive T-cell lymphoma as seen in our previous studies.
      Ingestion of caffeinated, but not decaffeinated, green tea provided modest but
      significant protection (P = 0.03) against mortality. Caffeine provided a more
      robust (P = 0.006) protection, but EGCG was without effect. Offspring also
      developed DBP-dependent lung adenomas. All treatments significantly reduced lung
      tumor multiplicity relative to controls (P < 0.02). EGCG was most effective at
      decreasing tumor burden (P = 0.005) by on average over 40% compared with
      controls. Induction of Cytochrome P450 (Cyp)1b1 in maternal liver may reduce
      bioavailability of DBP to the fetus as a mechanism of chemoprevention. This is
      the first demonstration that maternal ingestion of green tea, during pregnancy
      and nursing, provides protection against transplacental carcinogenesis.

PMID- 18635526
TI  - Survivin expression in normal human bronchial epithelial cells: an early and
      critical step in tumorigenesis induced by tobacco exposure.
AB  - The inhibitor of apoptosis protein survivin is selectively expressed in tumor
      cells. The tobacco component nicotine increases the transcription of the survivin
      gene in non-small cell lung cancer cells. However, the role of survivin
      expression induced by tobacco component is not clear during lung carcinogenesis.
      We investigated the effects of the tobacco components nicotine and its related
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on survivin
      expression in normal human bronchial epithelial (NHBE) cells and examined the
      role of survivin in the malignant transformation of normal human bronchial
      epithelial (HBE) cells induced by these components. We found that survivin
      messenger RNA (mRNA) expression was detected in 41% (7 of 17) of bronchial brush
      specimens from heavy smokers. Nicotine and NNK increased survivin mRNA and
      protein expression levels in primary cultured NHBE cells and immortalized HBE
      cells. Bronchial epithelium in mice administered NNK also showed increased
      staining for survivin. Nicotine and NNK stimulated the Akt-mammalian target of
      rapamycin (mTOR) pathway in NHBE cells, leading to increased de novo synthesis of
      survivin protein. Induced survivin expression increased the survival potential of
      the cells, which was blocked by transfection with survivin-specific small
      interfering RNA (siRNA). siRNA-induced down-regulation of survivin expression
      also suppressed the tumorigenic potential of premalignant and malignant HBE cells
      exposed to the tobacco components. These findings suggest that NNK and nicotine
      induce survivin protein synthesis in NHBE cells by activating the Akt-mTOR
      pathway and thus blockade of the pathway effectively inhibits the tobacco-induced
      malignant transformation of HBE cells.

PMID- 18635528
TI  - Ovarian function after removal of an entire ovary for cryopreservation of pieces
      of cortex prior to gonadotoxic treatment: a follow-up study.
AB  - BACKGROUND: Ovarian function was studied in Danish patients who had ovarian
      tissue cryopreserved, and the patients' experiences with the procedure were
      investigated. METHODS: There were 92 women who had an entire ovary removed for
      cryopreservation 18-75 months earlier. Reasons included: breast cancer (n = 31;
      34%), Hodgkin's lymphoma (n = 23; 25%), bone marrow transplantation (BMT) (n =
      19; 21%) and others (n = 19; 21%). Patients completed a questionnaire, and
      transvaginal ultrasonic antral follicle count and serum analysis for follicle
      stimulating hormone (FSH) and anti-Mullerian hormone (AMH) were performed in 73
      women. RESULTS: In total, 11% of the BMT patients had normal ovarian function.
      Hodgkin's patients who only received ABVD (doxorubicin, bleomycin, vinblastine
      and dacarbazine) (n = 12) and 60% of the breast cancer patients showed little
      evidence of ovarian damage. Regular menstruation was shown to be a good indicator
      of ovarian function. The cryopreservation procedure rarely complicated cancer
      treatment (5%) and 84% felt comforted because they had potentially secured their
      fertility. CONCLUSIONS: Cryopreservation of ovarian tissue should be considered
      in young female patients with Hodgkin's lymphoma receiving more aggressive
      treatment than ABVD and in patients scheduled for BMT. The recommendation for
      breast cancer patient should be individualized. The cryopreservation process did
      not delay cancer treatment.

PMID- 18635527
TI  - Localization of sucrose synthase in developing seed and siliques of Arabidopsis
      thaliana reveals diverse roles for SUS during development.
AB  - This study investigated the roles of sucrose synthase (SUS) in developing seeds
      and siliques of Arabidopsis thaliana. Enzyme activity assays showed that SUS
      activity was highest in developing whole siliques and young rosette leaves
      compared with other tissues including mature leaves, stems, and flowers.
      Surprisingly, quantitative PCR analyses revealed little correlation between SUS
      activity and transcript expression, which indicated the importance of examining
      the role of SUS at the protein level. Therefore, immunolocalization was performed
      over a developmental time course to determine the previously unreported cellular
      localization of SUS in Arabidopsis seed and silique tissues. At 3 d and 10 d
      after flowering (daf), SUS protein localized to the silique wall, seed coat,
      funiculus, and endosperm. By 13 daf, SUS protein was detected in the embryo and
      aleurone layer, but was absent from the seed coat and funiculus. Starch grains
      were also present in the seed coat at 3 and 10 daf, but were absent at 13 daf. Co
      localization of SUS protein and starch grains in the seed coat at 3 and 10 daf
      indicates that SUS may be involved in temporary starch deposition during the
      early stages of seed development, whilst in the later stages SUS metabolizes
      sucrose in the embryo and cotyledon. Within the silique wall, SUS localized
      specifically to the companion cells, indicating that SUS activity may be required
      to provide energy for phloem transport activities in the silique wall. The
      results highlight the diverse roles that SUS may play during the development of
      silique and seed in Arabidopsis.

PMID- 18635529
TI  - Treatment for cervical intraepithelial neoplasia and subsequent IVF deliveries.
AB  - BACKGROUND: The aim was to study whether the treatment of cervical
      intraepithelial neoplasia (CIN) is associated with a subsequent increase in the
      use of IVF to achieve deliveries and whether women with cervical treatment and
      IVF have increased rates of preterm delivery. METHODS: This was a register-based
      retrospective cohort (n = 822 183 deliveries) study from Finland whose main
      outcome measures were the rates of IVF and preterm deliveries in different CIN
      treatment groups. RESULTS: Of all deliveries in Finland, 1.5% (12 240) resulted
      from IVF treatment. This proportion was 1.6% for women who had undergone any
      cervical procedure [n = 150, risk ratio (RR): 1.21, confidence interval (CI):
      1.04-1.42]. The risk for IVF was not increased after cervical conization, whether
      by loop or laser (1.6%), or ablation (1.8%). An increased number of IVF
      deliveries (2.7%) was observed following other excisional treatments, even when
      adjusted for year of delivery (RR: 1.83, CI: 1.16-2.89) or parity (RR: 1.95, CI:
      1.25-3.04). Although women who had undergone any cervical procedure and IVF
      appeared to have an increased relative risk for preterm delivery (3.42-fold, CI:
      2.18-5.37) when compared with women with neither, this was explained by maternal
      age and parity. CONCLUSIONS: The proportion of IVF deliveries was not increased
      after cervical conization or ablation. This is reassuring for young women who
      undergo such treatments.

PMID- 18635531
TI  - Cardiometabolic risk in polycystic ovary syndrome: a comparison of different
      approaches to defining the metabolic syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with insulin
      resistance and features in common with the metabolic syndrome (MetS)--factors
      shown to predict cardiovascular risk and type 2 diabetes. We investigated the
      prevalence and characteristics of the MetS in PCOS by three definitions-World
      Health Organization (WHO), National Cholesterol Education Program Adult Treatment
      Panel III (NCEP-ATP-III) and International Diabetes Federation (IDF)--and
      compared that with the background population. METHODS: Cross-sectional study of
      168 women with PCOS and 883 age-matched controls from the Australian Diabetes,
      Obesity and Lifestyle (AusDiab) study. RESULTS: Prevalence of the MetS in PCOS
      subjects was 33% by WHO, 37% by NCEP-ATP-III and 40% by IDF criteria, compared
      with 10% by NCEP-ATP-III and 13% by IDF in controls (P < 0.001). MetS by WHO
      criteria was not calculated in the AusDiab population. Age was an independent
      predictor of MetS in PCOS and controls. The prevalence of MetS was significantly
      higher among those with PCOS (P = 0.027) in obese women (BMI > 30 kg/m(2)), and
      higher but not significantly so in overweight (BMI 25-30 kg/m(2)) women (P =
      0.052). Dehydroepiandrosterone sulphate was associated with a lower risk of the
      MetS--Odds ratio 0.86 (95% confidence interval, 0.77-0.97, P = 0.011).
      CONCLUSIONS: An approximate 4-fold increase in the prevalence of the MetS in
      women with PCOS compared with the general population, consistent with the
      proposed major role of insulin and obesity in the syndrome, implies greater risk
      of cardiometabolic disease in women with PCOS. However, this estimate is likely
      to vary according to PCOS definition, ethnicity and different aetiological
      pathways to PCOS.

PMID- 18635530
TI  - Regulation of MMP-9 by p53 in first trimester cytotrophoblastic cells.
AB  - BACKGROUND: The matrix metalloproteinase (MMP) family is known to play a key role
      in tissue remodelling during embryonic development and in pathological
      conditions, such as cardiovascular disease, arthritis and cancer metastasis. It
      has been shown previously that p53 regulates positively or negatively the
      expression of different MMPs. Because of p53 overexpression in trophoblastic
      cells, and its potential role in regulating MMP-2 and MMP-9 expression in
      different cell lines, we hypothesized that the expression of MMP-9 could also be
      regulated by p53 in first trimester cytotrophoblasts (CTB). METHODS AND RESULTS:
      Transfection experiments in CTB demonstrated that wild-type p53 down-regulates
      the -670 (P < 0.001) but not the -531 and -90 human MMP-9 promoter/CAT reporter
      plasmid activity, whereas p53 mutants partially lost this repressive activity.
      However, endogenous p53 is not able to regulate MMP-9 expression in CTB. The
      presence of high molecular weight complexes of p53 in CTB suggests a potential
      mechanism of inactivation of p53 transcriptional activity towards MMPs in these
      cells. CONCLUSIONS: Although p53 is mutated in trophoblast, it is functionally
      incompetent towards MMPs in these cells.

PMID- 18635532
TI  - Estrogen and progestogen receptor positive endometriotic lesions and disseminated
      cells in pelvic sentinel lymph nodes of patients with deep infiltrating
      rectovaginal endometriosis: a pilot study.
AB  - BACKGROUND: Deep infiltrating endometriosis (DIE) shows similarities to malignant
      diseases. A recent study involving DIE patients found endometriosis in mesorectal
      lymph nodes (LNs) after segmental bowel resection. However, it is unclear whether
      this observation is a local phenomenon or a sign of systemic disease. Therefore,
      we conducted a prospective study to investigate the occurrence of endometriosis
      in pelvic sentinel lymph nodes (SLNs) in patients with DIE. METHODS: Fourteen
      patients underwent primary surgery for symptomatic DIE. Combined vaginal
      laparoscopic-assisted resection of the rectovaginal septum was performed. Dye was
      injected into the visible/palpable nodule. SLNs were removed from the iliac
      region. In order to identify endometriotic cells, immunohistochemical analysis of
      estrogen and progestogen receptors, CD10 and cytokeratin was performed. RESULTS:
      In 12 out of 14 patients with DIE, SLNs were detected. The localization of the
      SLN followed the typical LN spread of the upper vagina. In three patients, we
      could detect typical endometriotic lesions in the LNs. Ten out of 12 (83.3%) SLNs
      showed disseminated estrogen and/or progestogen positive cells. CONCLUSIONS: By
      using immunohistochemistry, we could demonstrate endometriotic lesions and
      endometriotic-like cells in pelvic SLNs of patients with DIE suggesting the
      potential for lymphatic spread of the disease.

PMID- 18635533
TI  - Human Reproduction. Editor's note.

PMID- 18635534
TI  - DNA polymerase delta is highly processive with proliferating cell nuclear antigen
      and undergoes collision release upon completing DNA.
AB  - In most cells, 100-1000 Okazaki fragments are produced for each replicative DNA
      polymerase present in the cell. For fast-growing cells, this necessitates rapid
      recycling of DNA polymerase on the lagging strand. Bacteria produce long Okazaki
      fragments (1-2 kb) and utilize a highly processive DNA polymerase III (pol III),
      which is held to DNA by a circular sliding clamp. In contrast, Okazaki fragments
      in eukaryotes are quite short, 100-250 bp, and thus the eukaryotic lagging strand
      polymerase does not require a high degree of processivity. The lagging strand
      polymerase in eukaryotes, polymerase delta (pol delta), functions with the
      proliferating cell nuclear antigen (PCNA) sliding clamp. In this report,
      Saccharomyces cerevisiae pol delta is examined on model substrates to gain
      insight into the mechanism of lagging strand replication in eukaryotes.
      Surprisingly, we find pol delta is highly processive with PCNA, over at least 5
      kb, on Replication Protein A (RPA)-coated primed single strand DNA. The high
      processivity of pol delta observed in this report contrasts with its role in
      synthesis of short lagging strand fragments, which require it to rapidly
      dissociate from DNA at the end of each Okazaki fragment. We find that this
      dilemma is solved by a "collision release" process in which pol delta ejects from
      PCNA upon extending a DNA template to completion and running into the downstream
      duplex. The released pol delta transfers to a new primed site, provided the new
      site contains a PCNA clamp. Additional results indicate that the collision
      release mechanism is intrinsic to the pol3/pol31 subunits of the pol delta
      heterotrimer.

PMID- 18635535
TI  - The thermodynamics and kinetics of electron transfer between cytochrome b6f and
      photosystem I in the chlorophyll d-dominated cyanobacterium, Acaryochloris
      marina.
AB  - We have investigated the photosynthetic properties of Acaryochloris marina, a
      cyanobacterium distinguished by having a high level of chlorophyll d, which has
      its absorption bands shifted to the red when compared with chlorophyll a. Despite
      this unusual pigment content, the overall rate and thermodynamics of the
      photosynthetic electron flow are similar to those of chlorophyll a-containing
      species. The midpoint potential of both cytochrome f and the primary electron
      donor of photosystem I (P(740)) were found to be unchanged with respect to those
      prevailing in organisms having chlorophyll a, being 345 and 425 mV, respectively.
      Thus, contrary to previous reports (Hu, Q., Miyashita, H., Iwasaki, I. I.,
      Kurano, N., Miyachi, S., Iwaki, M., and Itoh, S. (1998) Proc. Natl. Acad. Sci. U.
      S. A. 95, 13319-13323), the midpoint potential of the electron donor P(740) has
      not been tuned to compensate for the decrease in excitonic energy in A. marina
      and to maintain the reducing power of photosystem I. We argue that this is a
      weaker constraint on the engineering of the oxygenic photosynthetic electron
      transfer chain than preserving the driving force for plastoquinol oxidation by
      P(740), via the cytochrome b(6)f complex. We further show that there is no
      restriction in the diffusion of the soluble electron carrier between cytochrome
      b(6)f and photosystem I in A. marina, at variance with plants. This difference
      probably reflects the simplified ultrastructure of the thylakoids of this
      organism, where no segregation into grana and stroma lamellae is observed.
      Nevertheless, chlorophyll fluorescence measurements suggest that there is energy
      transfer between adjacent photosystem II complexes but not from photosystem II to
      photosystem I, indicating spatial separation between the two photosystems.

PMID- 18635536
TI  - Pro-inflammatory secretory phospholipase A2 type IIA binds to integrins
      alphavbeta3 and alpha4beta1 and induces proliferation of monocytic cells in an
      integrin-dependent manner.
AB  - Secretory phospholipase A2 group IIA (sPLA2-IIA) plays an important role in the
      pathogenesis of inflammatory diseases. Catalytic activity of this enzyme that
      generates arachidonic acid is a major target for development of anti-inflammatory
      agents. Independent of its catalytic activity, sPLA2-IIA induces pro-inflammatory
      signals in a receptor-mediated mechanism (e.g. through the M-type receptor).
      However, the M-type receptor is species-specific: sPLA2-IIA binds to the M-type
      receptor in rodents and rabbits, but not in human. Thus sPLA2-IIA receptors in
      human have not been established. Here we demonstrated that sPLA2-IIA bound to
      integrin alphavbeta3 at a high affinity (K(D)=2 x 10(-7) M). We identified amino
      acid residues in sPLA2-IIA (Arg-74 and Arg-100) that are critical for integrin
      binding using docking simulation and mutagenesis. The integrin-binding site did
      not include the catalytic center or the M-type receptor-binding site. sPLA2-IIA
      also bound to alpha4beta1. We showed that sPLA2-IIA competed with VCAM-1 for
      binding to alpha4beta1, and bound to a site close to those for VCAM-1 and CS-1 in
      the alpha4 subunit. Wild type and the catalytically inactive H47Q mutant of sPLA2
      IIA induced cell proliferation and ERK1/2 activation in monocytic cells, but the
      integrin binding-defective R74E/R100E mutant did not. This indicates that
      integrin binding is required, but catalytic activity is not required, for sPLA2
      IIA-induced proliferative signaling. These results suggest that integrins
      alphavbeta3 and alpha4beta1 may serve as receptors for sPLA2-IIA and mediate pro
      inflammatory action of sPLA2-IIA, and that integrin-sPLA2-IIA interaction is a
      novel therapeutic target.

PMID- 18635537
TI  - YidC is involved in the biogenesis of anaerobic respiratory complexes in the
      inner membrane of Escherichia coli.
AB  - YidC of Escherichia coli belongs to the evolutionarily conserved Oxa1/Alb3/YidC
      family. Members of this family have all been implicated in membrane protein
      biogenesis of aerobic respiratory and energy-transducing proteins. YidC is
      essential for the insertion of subunit c of the F(1)F(0)-ATP synthase and subunit
      a of cytochrome o oxidase. The aim of this study was to investigate whether YidC
      plays a role during anaerobic growth of Escherichia coli, specifically when
      either nitrate or fumarate are used as terminal electron acceptors or under
      fermentative conditions. The effect of YidC depletion on the growth, enzyme
      activities, and protein levels in the inner membrane was determined. YidC is
      essential for all anaerobic growth conditions tested, and this is not because of
      the decreased levels of F(1)F(0)-ATP synthase in the inner membrane only. The
      results suggest a role for YidC in the membrane biogenesis of integral membrane
      parts of the anaerobic respiratory chain.

PMID- 18635538
TI  - Virus infection triggers SUMOylation of IRF3 and IRF7, leading to the negative
      regulation of type I interferon gene expression.
AB  - Viral infection activates Toll-like receptor and RIG-I (retinoic acid-inducible
      gene I) signaling pathways, leading to phosphorylation of IRF3 (interferon
      regulatory factor 3) and IRF7 and stimulation of type I interferon (IFN)
      transcription, a process important for innate immunity. We show that upon
      vesicular stomatitis virus infection, IRF3 and IRF7 are modified not only by
      phosphorylation but by the small ubiquitin-related modifiers SUMO1, SUMO2, and
      SUMO3. SUMOylation of IRF3 and IRF7 was dependent on the activation of Toll-like
      receptor and RIG-I pathways but not on the IFN-stimulated pathway. However,
      SUMOylation of IRF3 and IRF7 was not dependent on their phosphorylation, and vice
      versa. We identified Lys(152) of IRF3 and Lys(406) of IRF7 to be their sole small
      ubiquitin-related modifier (SUMO) conjugation site. IRF3 and IRF7 mutants
      defective in SUMOylation led to higher levels of IFN mRNA induction after viral
      infection, relative to the wild type IRFs, indicating a negative role for
      SUMOylation in IFN transcription. Together, SUMO modification is an integral part
      of IRF3 and IRF7 activity that contributes to postactivation attenuation of IFN
      production.

PMID- 18635539
TI  - Molecular shape, architecture, and size of P2X4 receptors determined using
      fluorescence resonance energy transfer and electron microscopy.
AB  - P2X receptors are ATP-gated nonselective cation channels with important
      physiological roles. However, their structures are poorly understood. Here, we
      analyzed the architecture of P2X receptors using fluorescence resonance energy
      transfer (FRET) microscopy and direct structure determination using electron
      microscopy. FRET efficiency measurements indicated that the distance between the
      C-terminal tails of P2X(4) receptors was 5.6 nm. Single particle analysis of
      purified P2X(4) receptors was used to determine the three-dimensional structure
      at a resolution of 21A; the orientation of the particle with respect to the
      membrane was assigned by labeling the intracellular C termini with 1.8-nm gold
      particles and the carbohydrate-rich ectodomain with lectin. We found that human
      P2X(4) is a globular torpedo-like molecule with an approximate volume of 270
      nm(3) and a compact propeller-shaped ectodomain. In this structure, the distance
      between the centers of the gold particles was 6.1 nm, which closely matches FRET
      data. Thus, our data provide the first views of the architecture, shape, and size
      of single P2X receptors, furthering our understanding of this important family of
      ligand-gated ion channels.

PMID- 18635540
TI  - Effects of redox potential and Ca2+ on the inositol 1,4,5-trisphosphate receptor
      L3-1 loop region: implications for receptor regulation.
AB  - Inositol 1,4,5-trisphosphate receptor (IP(3)R) is a major intracellular Ca(2+)
      channel, modulated by many factors in the cytosolic and lumenal compartments.
      Compared with cytosolic control, lumenal-side regulation has been much less
      studied, and some of its mechanistic aspects have been controversial. Of
      particular interest with regard to lumenal regulation are whether it involves
      direct interactions between IP(3)R and the regulators, and whether it involves
      conformational changes of the lumenal regions of IP(3)R. To understand these
      lumenal-side regulation mechanisms, we studied the effects of two important
      lumenal regulatory factors, the redox potential and Ca(2+), on the L3-1 lumenal
      loop region of IP(3)R. The redox potential exerted direct and significant effects
      on the conformation of the loop region. By sharp contrast, Ca(2+) showed little
      effect on the L3-1 conformation, suggesting that the regulation of Ca(2+) is
      indirect or involves other receptor regions. GSH/oxidized glutathione-mediated
      oxidation introduced a unique intramolecular disulfide bond between Cys(34) and
      Cys(42). A variety of NMR experiments revealed that oxidation also induces
      localized helical characteristics in the Cys(34)-Cys(42) region. Dynamics studies
      also showed reduced motions in the region upon oxidation, consistent with the
      conformational changes. The results raise the interesting possibility that
      Cys(34) and Cys(42) may act together as a reduction sensor, and that Cys(65) may
      function as an oxidation sensor. Overall, our studies suggest that the redox
      potential and Ca(2+) can regulate IP(3)R through totally different mechanisms:
      Ca(2+) by the indirect effect and the redox potential by direct action causing
      conformational changes.

PMID- 18635541
TI  - Early mitochondrial dysfunction in long-lived Mclk1+/- mice.
AB  - Reduced activity of CLK-1/MCLK1 (also known as COQ7), a mitochondrial enzyme that
      is necessary for ubiquinone biosynthesis, prolongs the lifespan of nematodes and
      mice by a mechanism that is distinct from that of the insulin signaling pathway.
      Here we show that 2-fold reduction of MCLK1 expression in mice reveals an
      additional function for the protein, as this level of reduction does not affect
      ubiquinone levels yet affects mitochondrial function substantially. Indeed, we
      observe that the phenotype of young Mclk1(+/-) mutants includes a severe
      reduction of mitochondrial electron transport, ATP synthesis, and total
      nicotinamide adenine dinucleotide (NAD(tot)) pool size as well as an alteration
      in the activity of key enzymes of the tricarboxylic acid cycle. Surprisingly, we
      also find that Mclk1 heterozygosity leads to a dramatic increase in mitochondrial
      oxidative stress by a variety of measures. Furthermore, we find that the
      mitochondrial dysfunction is accompanied by a decrease in oxidative damage to
      cytosolic proteins as well as by a decrease in plasma isoprostanes, a systemic
      biomarker of oxidative stress and aging. We propose a mechanism for the
      conjunction of low ATP levels, high mitochondrial oxidative stress, and low non
      mitochondrial oxidative damage in a long-lived mutant. Our model helps to clarify
      the relationship between energy metabolism and the aging process and suggests the
      need for a reformulation of the mitochondrial oxidative stress theory of aging.

PMID- 18635542
TI  - The nucleoside diphosphate kinase D (NM23-H4) binds the inner mitochondrial
      membrane with high affinity to cardiolipin and couples nucleotide transfer with
      respiration.
AB  - Nucleoside diphosphate kinase (NDPK/Nm23), responsible for intracellular di- and
      triphosphonucleoside homeostasis, plays multiple roles in cellular energetics,
      signaling, proliferation, differentiation and tumor invasion. The only human NDPK
      with a mitochondrial targeting sequence is NDPK-D, the NME4 gene product, which
      is a peripheral protein of mitochondrial membranes. Subfractionation of rat liver
      and HEK 293 cell mitochondria revealed that NDPK-D is essentially bound to the
      inner membrane. Surface plasmon resonance analysis of the interaction using
      recombinant NDPK-D and model liposomes showed that NDPK-D interacts
      electrostatically with anionic phospholipids, with highest affinity observed for
      cardiolipin. Mutation of the central arginine (Arg-90) in a surface-exposed basic
      RRK motif unique to NDPK-D strongly reduced interaction with anionic
      phospholipids. Due to its symmetrical hexameric structure, NDPK-D was able to
      cross-link anionic phospholipid-containing liposomes, suggesting that NDPK-D
      could promote intermembrane contacts. Latency assays with isolated mitochondria
      and antibody binding to mitoplasts indicated a dual orientation for NDPK-D. In
      HeLa cells, stable expression of wild type but not of the R90D mutant led to
      membrane-bound enzyme in vivo. Respiration was significantly stimulated by the
      NDPK substrate TDP in mitochondria containing wild-type NDPK-D, but not in those
      expressing the R90D mutant, which is catalytically equally active. This indicates
      local ADP regeneration in the mitochondrial intermembrane space and a tight
      functional coupling of NDPK-D with oxidative phosphorylation that depends on its
      membrane-bound state.

PMID- 18635543
TI  - Phosphorylation and ankyrin-G binding of the C-terminal domain regulate targeting
      and function of the ammonium transporter RhBG.
AB  - RhBG, a human member of the Amt/Mep/Rh/superfamily of ammonium transporters, has
      been shown to facilitate NH(3) transport and to be anchored to the basolateral
      plasma membrane of kidney epithelial cells, via ankyrin-G. We showed here that
      triple alanine substitution of the (419)FLD(421) sequence, which links the
      cytoplasmic C-terminal domain of RhBG to ankyrin-G, not only disrupted the
      interaction of RhBG with the spectrin-based skeleton but also delayed its cell
      surface expression, decreased its plasma membrane stability, and abolished its
      NH(3) transport function in epithelial cell lines. Similarly, we demonstrated
      that both anchoring to the membrane skeleton and ammonium transport activity are
      regulated by the phosphorylation status of the C-terminal tail of RhBG. Tyrosine
      429, which belongs to the previously reported YED basolateral targeting signal of
      RhBG, was demonstrated to be phosphorylated in vitro using purified Src and Syk
      kinases and ex vivo by analyzing the effect of pervanadate treatment on wild-type
      RhBG or Y429A mutants. Then, we showed that Y429D and Y429E mutations, mimicking
      constitutive phosphorylation, abolished NH(3) transport and enhanced Triton X-100
      solubilization of RhBG from the cell membrane. In contrast, the
      nonphosphorylated/nonphosphorylatable Y429A and Y429F mutants behaved the same as
      wild-type RhBG. Conversely, Y/A or Y/F but not Y/E or Y/D mutations of residue
      429 abolished the exclusive basolateral localization of RhBG in polarized
      epithelial cells. All these results led to a model in which targeting and
      ammonium transport function of RhBG are regulated by both phosphorylation and
      membrane skeleton binding of the C-terminal cytoplasmic domain.

PMID- 18635544
TI  - All domains of Cry1A toxins insert into insect brush border membranes.
AB  - A critical step in understanding the mode of action of insecticidal crystal
      toxins from Bacillus thuringiensis is their partitioning into membranes and, in
      particular, the insertion of the toxin into insect brush border membranes. The
      Umbrella and Penknife models predict that only alpha-helix 5 of domain I along
      with adjacent helices alpha-4 or alpha-6 insert into the brush border membranes
      because of their hydrophobic nature. By employing fluorescent-labeled cysteine
      mutations, we observe that all three domains of the toxin insert into the insect
      membrane. Using proteinase K protection assays, steady state fluorescence
      quenching measurements, and blue shift analysis of acrylodan-labeled cysteine
      mutants, we show that regions beyond those proposed by the two models insert into
      the membrane. Based on our studies, the only extended region that does not
      partition into the membrane is that of alpha-helix 1. Bioassays and voltage
      clamping studies show that all mutations examined, except certain domain II
      mutations in loop 2 (e.g. F371C and G374C), which disrupt membrane partitioning,
      retain their ability to form ion channels and toxicity in Manduca sexta larvae.
      This study confirms our earlier hypothesis that insertion of crystal toxin does
      not occur as separate helices alone, but virtually the entire molecule inserts as
      one or more units of the whole molecule.

PMID- 18635545
TI  - Location and function of STIM1 in the activation of Ca2+ entry signals.
AB  - Store-operated channels (SOCs) mediate Ca(2+) entry signals in response to
      endoplasmic reticulum (ER) Ca(2+) depletion in most cells. STIM1 senses decreased
      ER luminal Ca(2+) through its EF-hand Ca(2+)-binding motif and aggregates in near
      plasma membrane (PM) ER junctions to activate PM Orai1, the functional SOC. STIM1
      is also present in the PM, although its role there is unknown. STIM1-mediated
      coupling was examined using the stable EF20 HEK293 cell line expressing the STIM1
      D76A/E87A EF-hand mutant (STIM1(EF)) deficient in Ca(2+) binding. EF20 cells were
      viable despite constitutive Ca(2+) entry, allowing study of SOC activation
      without depleting ER Ca(2+). STIM1(EF) was exclusively in stable near-PM
      junctions, 3.5-fold larger than formed with STIM1(WT). STIM(EF)-expressing cells
      had normal ER Ca(2+) levels but substantially reduced ER Ca(2+) leak. Expression
      of antiapoptotic Bcl-2 proteins (BCl-2, MCL-1, BCL-XL) were increased 2-fold in
      EF20 cells, probably reflecting survival of EF20 cells but not accounting for
      decreased ER Ca(2+) leak. Surface biotinylation and streptavidin pull-down of
      cells expressing STIM1(WT) or STIM1(EF) revealed strong PM interactions of both
      proteins. Although surface expression of STIM1(WT) was clearly detectable,
      STIM1(EF) was undetectable at the cell surface. Thus, the Ca(2+) binding
      defective STIM1(EF) mutant exists exclusively in aggregates within near-PM
      junctions but, unlike STIM1(WT), is not trafficked to the PM. Although not
      inserted in the PM, external application of a monoclonal anti-N-terminal STIM1
      antibody blocked constitutive STIM(EF)-mediated Ca(2+) entry, but only in cells
      expressing endogenous STIM1(WT) and not in DT40 STIM1 knock-out cells devoid of
      STIM(WT). This suggests that PM-STIM1 may play a regulatory role in SOC
      activation.

PMID- 18635546
TI  - Root-microbe communication through protein secretion.
AB  - Biotic interactions in the rhizosphere are biologically important, and although
      many of those interactions have been well studied, the role of secreted proteins
      in the cross-talk between microbes and roots has not been investigated. Here,
      protein secretion was studied during the communication between the roots of two
      plants (Medicago sativa and Arabidopsis thaliana) and the bacterial symbiont of
      one of these species (Sinorhizobium meliloti strain Rm1021) and an opportunistic
      bacterial pathogen of A. thaliana (Pseudomonas syringae pv. tomato DC3000) using
      a proteomic approach. It was found that protein exudation in the M. sativa-S.
      meliloti interaction caused an increase in the secretion of seven plant proteins,
      such as hydrolases, peptidases, and peroxidases among others in two or more time
      points compared with the plant control. In addition, four proteins, all of
      bacterial origin, were increased 1.5-fold more in this interaction compared with
      S. meliloti alone. However, these proteins were not induced when M. sativa was
      inoculated with P. syringae DC3000. The interaction between A. thaliana and P.
      syringae DC3000 highly induced the secretion of several plant proteins related to
      defense soon after initial contact with P. syringae, but these proteins were not
      secreted in the incompatible interaction with S. meliloti. The results of this
      study reveal a specific, protein level cross-talk between roots and microbes.
      These results suggest that secreted proteins may be a critical component in the
      process of signaling and recognition that occurs between compatible and
      incompatible interactions.

PMID- 18635547
TI  - Pin1-dependent prolyl isomerization modulates the stress-induced phosphorylation
      of high molecular weight neurofilament protein.
AB  - Aberrant phosphorylation of neuronal cytoskeletal proteins is a key pathological
      event in neurodegenerative disorders such as Alzheimer disease (AD) and
      amyotrophic lateral sclerosis, but the underlying mechanisms are still unclear.
      Previous studies have shown that Pin1, a peptidylprolyl cis/trans-isomerase, may
      be actively involved in the regulation of Tau hyperphosphorylation in AD. Here,
      we show that Pin1 modulates oxidative stress-induced NF-H phosphorylation. In an
      in vitro kinase assay, the addition of Pin1 substantially increased
      phosphorylation of NF-H KSP repeats by proline-directed kinases, Erk1/2,
      Cdk5/p35, and JNK3 in a concentration-dependent manner. In vivo, dominant
      negative (DN) Pin1 and Pin1 small interfering RNA inhibited epidermal growth
      factor-induced NF-H phosphorylation. Because oxidative stress plays an important
      role in the pathogenesis of neurodegenerative diseases, we studied the role of
      Pin1 in stressed cortical neurons and HEK293 cells. Both hydrogen peroxide
      (H(2)O(2)) and heat stresses induce phosphorylation of NF-H in transfected HEK293
      cells and primary cortical cultures. Knockdown of Pin1 by transfected Pin1 short
      interference RNA and DN-Pin1 rescues the effect of stress-induced NF-H
      phosphorylation. The H(2)O(2) and heat shock induced perikaryal phospho-NF-H
      accumulations, and neuronal apoptosis was rescued by inhibition of Pin1 in
      cortical neurons. JNK3, a brain-specific JNK isoform, is activated under
      oxidative and heat stresses, and inhibition of Pin1 by Pin1 short interference
      RNA and DN-Pin1 inhibits this pathway. These results implicate Pin1 as a possible
      modulator of stress-induced NF-H phosphorylation as seen in neurodegenerative
      disorders like AD and amyotrophic lateral sclerosis. Thus, Pin1 may be a
      potential therapeutic target for these diseases.

PMID- 18635548
TI  - CD95 stimulation results in the formation of a novel death effector domain
      protein-containing complex.
AB  - Stimulation of CD95 (APO-1/Fas) by its natural ligand CD95L (APO-1L/FasL) leads
      to the formation of the death-inducing signaling complex. Here we report that
      upon CD95 stimulation in several T and B cell lines, a novel signaling complex is
      formed, which we term complex II. Complex II is composed of the death effector
      domain proteins as follows: procaspase-8a/b, three isoforms of c-FLIP (c-FLIP(L),
      c-FLIP(S), c-FLIP(R)), and FADD. Notably, complex II does not contain CD95. Based
      on our findings we suggest that CD95 signaling includes two steps. The first step
      involves formation of the death-inducing signaling complex at the cell membrane.
      The second step involves formation of the cytosolic death effector domain protein
      containing complex that may play an important role in amplification of caspase
      activation.

PMID- 18635550
TI  - Functional chimeras of the phosphodiesterase 5 and 10 tandem GAF domains.
AB  - The tandem GAF domain of hPDE10A uses cAMP as an allosteric ligand (Gross
      Langenhoff, M., Hofbauer, K., Weber, J., Schultz, A., and Schultz, J. E. (2006)
      J. Biol. Chem. 281, 2841-2846). We used a two-pronged approach to study how
      discrimination of ligand is achieved in human (h)PDE10A and how domain selection
      in the phosphodiesterase GAF tandems is determined. First, we examined which
      functional groups of cAMP are responsible for purine ring discrimination. Changes
      at the C-6 ring position (removal of the amino group; chloride substitution) and
      at the N-1 ring position reduced stimulation efficacy by 80%, i.e. marking those
      positions as decisive for nucleotide discrimination. Second, we generated a GAF
      tandem chimera that consisted of the cGMP-binding GAF-A unit from hPDE5A1, which
      signals through cGMP in PDE5, and the GAF-B from hPDE10A1, which signals through
      cAMP in PDE10. Stimulation of the reporter enzyme exclusively was through the GAF
      B domain of hPDE10A1 (EC(50) = 7 microm cAMP) as shown by respective point
      mutations. The PDE5 GAF-A domain in the chimera did not signal, and its function
      was reduced to a strictly structural role. Signaling was independent of the
      origin of the N terminus. Generating 10 additional PDE5/10 tandem GAF chimeras
      surprisingly demonstrated that the length-conserved linker in GAF tandems between
      GAF-A and GAF-B played an unforeseen decisive role in intramolecular signaling.
      Swapping the linker sections between PDE5 and PDE10 GAF tandem domains abrogated
      signaling completely pointing to specific domain interactions within GAF tandems,
      which are not visible in the available crystal structures with bound ligands.

PMID- 18635549
TI  - Tumor necrosis factor-alpha can provoke cleavage and activation of sterol
      regulatory element-binding protein in ethanol-exposed cells via a caspase
      dependent pathway that is cholesterol insensitive.
AB  - Ethanol induces the development of hepatic steatosis, increasingly recognized as
      causing vulnerability to subsequent liver injury. Ethanol has been shown to
      activate SREBP-1 (sterol regulatory element-binding protein) processing through
      the conventional cholesterol-sensitive pathway (1). The present study
      demonstrates that ethanol can also bring about SREBP-1 cleavage and activation
      through a novel pathway dependent on the endoplasmic reticulum-localized caspases
      4 and -12. Evidence is presented that tumor necrosis factor can stimulate caspase
      4 and -12 activation in ethanol-exposed cells, which cleaves SREBP-1 to a
      transcriptionally active form to induce the synthesis of lipogenic enzymes and
      triglycerides. Moreover, the caspase-4 and -12-dependent activation of SREBP-1 is
      insensitive to the normal negative feedback exerted by cholesterol and is
      mediated by the translocation of the scaffolding protein, TRAF-2, to the
      endoplasmic reticulum.

PMID- 18635551
TI  - Exendin-(9-39) corrects fasting hypoglycemia in SUR-1-/- mice by lowering cAMP in
      pancreatic beta-cells and inhibiting insulin secretion.
AB  - Congenital hyperinsulinism is a disorder of pancreatic beta-cell function
      characterized by failure to suppress insulin secretion in the setting of
      hypoglycemia, resulting in brain damage or death if untreated. Loss-of-function
      mutations in the K(ATP) channel (composed of two subunits: Kir6.2 and SUR-1) are
      responsible for the most common and severe form of congenital hyperinsulinism.
      Most patients are unresponsive to available medical therapy and require
      palliative pancreatectomy. Similar to the human condition, the SUR-1(-/-) mouse
      is hypoglycemic when fasted and hyperglycemic when glucose-loaded. We have
      previously reported that the glucagon-like peptide-1 receptor antagonist exendin
      (9-39) raises fasting blood glucose in normal mice. Here we examine the effect of
      exendin-(9-39) on fasting blood glucose in SUR-1(-/-) mice. Mice were randomized
      to receive exendin-(9-39) or vehicle. Fasting blood glucose levels in SUR-1(-/-)
      mice treated with exendin-(9-39) were significantly higher than in vehicle
      treated mice and not different from wild-type littermates. Exendin-(9-39) did not
      further worsen glucose tolerance and had no effect on body weight and insulin
      sensitivity. Isolated islet perifusion studies demonstrated that exendin-(9-39)
      blocked amino acid-stimulated insulin secretion, which is abnormally increased in
      SUR-1(-/-) islets. Furthermore, cAMP content in SUR-1(-/-) islets was reduced by
      exendin-(9-39) both basally and when stimulated by amino acids, whereas cytosolic
      calcium levels were not affected. These findings suggest that cAMP plays a key
      role in K(ATP)-independent insulin secretion and that the GLP-1 receptor is
      constitutively active in SUR-1(-/-) beta-cells. Our findings indicate that
      exendin-(9-39) normalizes fasting hypoglycemia in SUR-1(-/-) mice via a direct
      effect on insulin secretion, thereby raising exendin-(9-39) as a potential
      therapeutic agent for K(ATP) hyperinsulinism.

PMID- 18635552
TI  - Long patch base excision repair in mammalian mitochondrial genomes.
AB  - The mitochondrial genome is highly susceptible to damage by reactive oxygen
      species (ROS) generated endogenously as a byproduct of respiration. ROS-induced
      DNA lesions, including oxidized bases, abasic (AP) sites, and oxidized AP sites,
      cause DNA strand breaks and are repaired via the base excision repair (BER)
      pathway in both the nucleus and mitochondria. Repair of damaged bases and AP
      sites involving 1-nucleotide incorporation, named single nucleotide (SN)-BER, was
      observed with mitochondrial and nuclear extracts. During SN-BER, the 5'
      phosphodeoxyribose (dRP) moiety, generated by AP-endonuclease (APE1), is removed
      by the lyase activity of DNA polymerase gamma (pol gamma) and polymerase beta in
      the mitochondria and nucleus, respectively. However, the repair of oxidized
      deoxyribose fragments at the 5' terminus after strand break would require 5'
      exo/endonuclease activity that is provided by the flap endonuclease (FEN-1) in
      the nucleus, resulting in multinucleotide repair patch (long patch (LP)-BER).
      Here we show the presence of a 5'-exo/endonuclease in the mitochondrial extracts
      of mouse and human cells that is involved in the repair of a lyase-resistant AP
      site analog via multinucleotide incorporation, upstream and downstream to the
      lesion site. We conclude that LP-BER also occurs in the mitochondria requiring
      the 5'-exo/endonuclease and pol gamma with 3'-exonuclease activity. Although a
      FEN-1 antibody cross-reacting species was detected in the mitochondria, it was
      absent in the LP-BER-proficient APE1 immunocomplex isolated from the
      mitochondrial extract that contains APE1, pol gamma, and DNA ligase 3. The LP-BER
      activity was marginally affected in FEN-1-depleted mitochondrial extracts,
      further supporting the involvement of an unidentified 5'-exo/endonuclease in
      mitochondrial LP-BER.

PMID- 18635553
TI  - Triggering aggresome formation. Dissecting aggresome-targeting and aggregation
      signals in synphilin 1.
AB  - Abnormal polypeptides that escape proteasome-dependent degradation and aggregate
      in cytosol can be transported via microtubules to an aggresome, a recently
      discovered organelle where aggregated proteins are stored or degraded by
      autophagy. We used synphilin 1, a protein implicated in Parkinson disease, as a
      model to study mechanisms of aggresome formation. When expressed in naive HEK293
      cells, synphilin 1 forms multiple small highly mobile aggregates. However,
      proteasome or Hsp90 inhibition rapidly triggered their translocation into the
      aggresome, and surprisingly, this response was independent on the expression
      level of synphilin 1. Therefore, aggresome formation, but not aggregation of
      synphilin 1, represents a special cellular response to a failure of the
      proteasome/chaperone machinery. Importantly, translocation to aggresomes required
      a special aggresome-targeting signal within the sequence of synphilin 1, an
      ankyrin-like repeat domain. On the other hand, formation of multiple small
      aggregates required an entirely different segment within synphilin 1, indicating
      that aggregation and aggresome formation determinants can be separated
      genetically. Furthermore, substitution of the ankyrin-like repeat in synphilin 1
      with an aggresome-targeting signal from huntingtin was sufficient for aggresome
      formation upon inhibition of the proteasome. Analogously, attachment of the
      ankyrin-like repeat to a huntingtin fragment lacking its aggresome-targeting
      signal promoted its transport to aggresomes. These findings indicate the
      existence of transferable signals that target aggregation-prone polypeptides to
      aggresomes.

PMID- 18635554
TI  - Single histidine-substituted cardiac troponin I confers protection from age
      related systolic and diastolic dysfunction.
AB  - AIMS: Contractile dysfunction associated with myocardial ischaemia is a
      significant cause of morbidity and mortality in the elderly. Strategies to
      protect the aged heart from ischaemia-mediated pump failure are needed. We
      hypothesized that troponin I-mediated augmentation of myofilament calcium
      sensitivity would protect cardiac function in aged mice. METHODS AND RESULTS: To
      address this, we investigated transgenic (Tg) mice expressing a histidine
      substituted form of adult cardiac troponin I (cTnI A164H), which increases
      myofilament calcium sensitivity in a pH-dependent manner. Serial echocardiography
      revealed that Tg hearts showed significantly improved systolic function at 4
      months, which was sustained for 2 years based on ejection fraction and velocity
      of circumferential fibre shortening. Age-related diastolic dysfunction was also
      attenuated in Tg mice as assessed by Doppler measurements of the mitral valve
      inflow and lateral annulus Doppler tissue imaging. During acute hypoxia, cardiac
      contractility significantly improved in aged Tg mice made evident by increased
      stroke volume, end systolic pressure, and +dP/dt compared with non-transgenic
      mice. CONCLUSION: This study shows that increasing myofilament function by means
      of a pH-responsive histidine button engineered into cTnI results in enhanced
      baseline heart function in Tg mice over their lifetime, and during acute hypoxia
      improves survival in aged mice by maintaining cardiac contractility.

PMID- 18635556
TI  - Comparison of identified mitral and tufted cells in freely breathing rats: I.
      Conduction velocity and spontaneous activity.
AB  - The spontaneous activity and impulse conduction velocities of mitral and tufted
      cells were compared in the entire main olfactory bulb of freely breathing,
      anesthetized rats. Single units in the mitral cell body layer (MCL) and external
      plexiform layer (EPL) were identified by antidromic activation from the lateral
      olfactory tract (LOT), electrode track reconstructions based on dye marking, and
      the waveform of LOT-evoked field potentials. Using the track reconstructions, EPL
      units were further subdivided into glomerular border (GB) and not at the
      glomerular border (notGB) cells. For conduction velocity, significant differences
      were only found between MCL and GB units and not between MCL and all EPL units or
      between MCL and notGB units. For spontaneous activity, no significant differences
      were found between the different unit groups regarding the mean, maximum, or
      relative maximum rate per 100-ms bin. By contrast, they showed a differential
      modulation of their firing activity by respiration. GB but not notGB units had a
      significantly higher mean rate during the respiratory cycle than MCL units with
      significantly more activity during inspiration. Thus, mitral and tufted cells are
      similar in their impulse conduction velocity and spontaneous activity, though the
      more superficially placed GB cells exhibit differences. A comparison of odor
      responses in these cell types in the companion paper also points to differences
      between mitral and superficial projection tufted cells.

PMID- 18635555
TI  - Pharmacological investigation of protein kinase C- and cGMP-dependent ion
      channels in cultured olfactory receptor neurons of the hawkmoth Manduca sexta.
AB  - In the hawkmoth Manduca sexta, pheromone stimuli of different strength and
      duration rise the intracellular Ca2+ concentration in olfactory receptor neurons
      (ORNs). While second-long pheromone stimuli activate protein kinase C (PKC),
      which apparently underlies processes of short-term adaptation, minute-long
      pheromone stimuli elevate cyclic guanosine monophosphate (cGMP) concentrations,
      which correlates with time courses of long-term adaptation. To identify ion
      channels involved in the sliding adjustment of olfactory sensitivity, inside-out
      patch clamp recordings on cultured ORNs of M. sexta were performed to
      characterize Ca2+-, PKC-, and cGMP-dependent ion channels. Stepping to positive
      holding potentials in high intracellular Ca2+ elicits different Ca2+-dependent
      ion channels, namely small-conductance channels (2-20 ps), medium-conductance
      channels (20-100 ps), and large-conductance channels (>100 ps). Ion channels of
      40, 60, and 70 ps opened after PKC activation, whereas 10- and >100-ps channels
      were observed less frequently. Application of 8-bromo cyclic guanosine
      monophosphate opened 55- and 70-ps channels and increased the open probability of
      >100-ps channels, whereas even in the presence of phorbol ester 40-ps channels
      were inhibited. Thus, cGMP elevations activate a different set of ion channels as
      compared with PKC and suppress at least one PKC-dependent ion channel.

PMID- 18635558
TI  - Genotoxicity of 3-nitrobenzanthrone and 3-aminobenzanthrone in MutaMouse and lung
      epithelial cells derived from MutaMouse.
AB  - FE1 lung epithelial cells derived from MutaMouse are a new model system to
      provide in vitro mutagenicity data with the potential to predict the outcome of
      an in vivo MutaMouse test. 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and
      suspected human carcinogen identified in diesel exhaust and urban air pollution.
      We investigated the mutagenicity and DNA binding of 3-NBA and its main metabolite
      3-aminobenzanthrone (3-ABA) in vitro and in vivo in the MutaMouse assay. Mice
      were treated with 3-NBA or 3-ABA (0, 2 or 5 mg/kg body weight/day) by gavage for
      28 days and 28 days later lacZ mutant frequency (MF) was determined in liver,
      lung and bone marrow. For both compounds, dose-related increases in MF were seen
      in liver and bone marrow, but not in lung; mutagenic activity was approximately 2
      fold lower for 3-ABA than for 3-NBA. With 3-NBA, highest DNA adduct levels
      (measured by (32)P-post-labelling) were found in liver (approximately 230 adducts
      per 10(8) nucleotides) with levels 20- to 40-fold lower in bone marrow and lung.
      With 3-ABA, DNA adduct levels were again highest in the liver, but approximately
      4-fold lower than for 3-NBA. FE1 cells were exposed to up to 10 microg/ml 3-NBA
      or 3-ABA for 6 h with or without exogenous activation (S9) and harvested after 3
      days. For 3-NBA, there was a dose-related increase in MF both with and without S9
      mix, which was >10 times higher than observed in vivo. At the highest
      concentration of 3-ABA (10 microg/ml), we found only around a 2-fold increase in
      MF relative to controls. DNA adduct formation in FE1 cells was dose-dependent for
      both compounds, but 10- to 20-fold higher for 3-NBA compared to 3-ABA.
      Collectively, our data indicate that MutaMouse FE1 cells are well suited for cost
      effective testing of suspected mutagens with different metabolic activation
      pathways as a guide for subsequent in vivo MutaMouse testing.

PMID- 18635559
TI  - Update on thoracic anesthesia: where are we today?

PMID- 18635557
TI  - Greater superficial petrosal nerve transection in rats does not change
      unconditioned licking responses to putatively sweet taste stimuli.
AB  - The greater superficial petrosal nerve (GSP), innervating taste buds in the
      palate, is known to be exceptionally responsive to sucrose, especially compared
      with the responsiveness of the chorda tympani nerve (CT). However, whereas
      transection of the CT (CTX) alone has little or no effect on unconditioned
      licking responses to many "sweet" stimuli, the impact of GSP transection (GSPX)
      alone is equivocal. To further examine the role of the GSP on licking responses
      to putatively sweet-tasting substances, brief-access taste tests were conducted
      in nondeprived rats before and after sham surgery (SHAM) or CTX or GSPX. A range
      of concentrations of sucrose, L-alanine, glycine, and L-serine, with and without
      1.0 mM inosine monophosphate (IMP) added, were used. All groups showed
      significant concentration-dependent increases in licking to all stimuli
      presurgically and postsurgically. CTX decreased licking responses relative to
      SHAM rats in the first sucrose test. There was also a group x concentration
      interaction for L-alanine, but post hoc tests did not reveal its basis. Other
      than this, there were no significant differences among the surgical groups.
      Interestingly, rats with GSPX tended to initiate fewer trials than SHAM rats.
      Overall, after GSPX, the remaining gustatory nerves are apparently sufficient to
      maintain concentration-dependent licking responses to all stimuli tested here.
      The disparity between our results and others in the literature where GSPX reduced
      licking responses to sucrose is possibly related to differences in surgical
      technique or test trial duration.

PMID- 18635560
TI  - Anesthetic management of patients with pulmonary hypertension.
AB  - Advances in the treatment of patients with chronic pulmonary hypertension have
      greatly improved their functional status and longevity, and increasing numbers of
      these complex patients are presenting for elective noncardiac surgery. In this
      communication we will briefly review the classification and pathophysiology of
      pulmonary hypertension, summarize outpatient pharmacotherapy approaches, and
      discuss the perioperative preparation and management of these complex patients.
      With an understanding of the underlying pathophysiology of the disease and
      pharmacology of these new therapies, combined with careful perioperative planning
      and care, these patients can safely undergo elective surgical procedures.

PMID- 18635561
TI  - Appropriate ventilatory settings for thoracic surgery: intraoperative and
      postoperative.
AB  - Mechanical ventilation of patients undergoing thoracic surgery is often
      challenging. These patients frequently have significant underlying comorbidities,
      including cardiopulmonary disease, and often must undergo 1-lung ventilation.
      Perioperative respiratory complications are common and are multifactorial in
      etiology. Increasing evidence suggests that mechanical ventilation is associated
      with, and may even cause, lung damage in both sick and healthy patients. Gas
      exchange to provide acceptable end-organ oxygenation remains a primary goal but
      so too is minimization of risks for acute lung injury. Every ventilator strategy
      is associated with potential beneficial and adverse side effects. Understanding
      the impact of various ventilation strategies allows clinicians to provide optimal
      care for patients.

PMID- 18635562
TI  - Preoperative evaluation for thoracic surgery.
AB  - The goal of the preoperative evaluation for thoracic surgery is to assess and
      implement measures to decrease perioperative complications and prepare high-risk
      patients for surgery. Major respiratory complications, such as atelectasis,
      pneumonia, and respiratory failure, occur in 15% to 20% of patients and account
      for most of the 3% to 4% mortality rate. Development of pulmonary complications
      has been associated with higher postoperative mortality rates. Strategies aimed
      at preventing postoperative difficulties have the potential to reduce morbidity
      and mortality, decrease hospital stay, and improve resource use. One lung
      ventilation leads to a significant derangement of gas exchange, and hypoxemia can
      develop due to increased intrapulmonary shunting. Recent advances in anesthetic
      management, monitoring devices, improved lung isolation techniques, and improved
      critical care management have increased the number of patients who were
      previously considered inoperable. In addition, there is a growing tendency to
      offer surgery to patients with significant lung function impairment; hence a
      higher incidence of intraoperative gas-exchange abnormalities can be expected.
      The anesthesiologist must also consider the risks of denying or postponing a
      potentially curative operation in patients with lung cancer. Detailed
      consideration of the information provided by preoperative testing is essential to
      successful outcomes following thoracic surgery.

PMID- 18635563
TI  - Anesthetic considerations for lung transplantation.
AB  - Lung transplantation is the definitive treatment for end-stage lung disease. The
      number of lung transplantations performed is limited by the number of donors
      available and is far outnumbered by the potential recipients on the waiting list.
      Advances in surgical methods, organ preservation, and immunosuppression have
      decreased the morbidity and mortality associated with this procedure during the
      last few decades. Specific anesthetic concerns are associated with lung
      transplantation, including careful preoperative assessment of pulmonary and
      cardiac function, adequate venous access and monitors, and ventilation
      techniques, such as 1-lung ventilation and lung-protective strategies to decrease
      the risks of reperfusion injury, barotrauma, and re-expansion pulmonary edema.
      Intraoperative transesophageal echocardiography, cardiopulmonary bypass, and
      inhaled nitric oxide can also be important tools for the anesthesiologist to
      optimize patient care during this challenging procedure.

PMID- 18635564
TI  - Mediastinoscopy and video-assisted thoracoscopic surgery: anesthetic pitfalls and
      complications.
AB  - Endoscopic evaluation of the thoracic cavity was first described in 1910 when
      Jacobaeus used a cystoscope for pleural examination. Significant advances in
      thoracoscopic surgery, including the use of high-definition videoscopy and
      refinements in surgical technique, have created a vast array of increasingly
      complex procedures that can be performed. The minimally invasive nature of video
      assisted thoracoscopic surgery (VATS) makes it ideal for diagnostic and
      therapeutic procedures in ambulatory and critically ill patients. Mediastinoscopy
      is often performed immediately preceding VATS to permit sampling of mediastinal
      lymph nodes. As the indications for thoracoscopic surgery expand, the
      anesthesiologist must be familiar with common anesthetic and surgical
      complications, which occur in up to 9% of patients.

PMID- 18635565
TI  - Considering dependence among genes and markers for false discovery control in
      eQTL mapping.
AB  - MOTIVATION: Multiple comparison adjustment is a significant and challenging
      statistical issue in large-scale biological studies. In previous studies,
      dependence among genes is largely ignored. However, such dependence may be strong
      for some genomic-scale studies such as genetical genomics [also called expression
      quantitative trait loci (eQTL) mapping] in which thousands of genes are treated
      as quantitative traits and mapped to different genetical markers. Besides the
      dependence among markers, the dependence among the expression levels of genes can
      also have a significant impact on data analysis and interpretation. RESULTS: In
      this article, we propose to consider both the mean as well as the variance of
      false discovery number for multiple comparison adjustment to handle dependence
      among hypotheses. This is achieved by developing a variance estimator for false
      discovery number, and using the upper bound of false discovery proportion (uFDP)
      for false discovery control. More importantly, we introduce a weighted version of
      uFDP (wuFDP) control to improve the statistical power of eQTL identification. In
      addition, the wuFDP approach can better control false positives than false
      discovery rate (FDR) and uFDP approaches when markers are in linkage
      disequilibrium. The relative performance of uFDP control and wuFDP control is
      illustrated through simulation studies and real data analysis. SUPPLEMENTARY
      INFORMATION: Supplementary figures, tables and appendices are available at
      Bioinformatics online.

PMID- 18635566
TI  - ProCope--protein complex prediction and evaluation.
AB  - SUMMARY: Recent advances in high-throughput technology have increased the
      quantity of available data on protein complexes and stimulated the development of
      many new prediction methods. In this article, we present ProCope, a Java software
      suite for the prediction and evaluation of protein complexes from affinity
      purification experiments which integrates the major methods for calculating
      interaction scores and predicting protein complexes published over the last
      years. Methods can be accessed via a graphical user interface, command line tools
      and a Java API. Using ProCope, existing algorithms can be applied quickly and
      reproducibly on new experimental results, individual steps of the different
      algorithms can be combined in new and innovative ways and new methods can be
      implemented and integrated in the existing prediction framework. AVAILABILITY:
      Source code and executables are available at
      http://www.bio.ifi.lmu.de/Complexes/ProCope/.

PMID- 18635567
TI  - A comparative study of survival models for breast cancer prognostication based on
      microarray data: does a single gene beat them all?
AB  - MOTIVATION: Survival prediction of breast cancer (BC) patients independently of
      treatment, also known as prognostication, is a complex task since clinically
      similar breast tumors, in addition to be molecularly heterogeneous, may exhibit
      different clinical outcomes. In recent years, the analysis of gene expression
      profiles by means of sophisticated data mining tools emerged as a promising
      technology to bring additional insights into BC biology and to improve the
      quality of prognostication. The aim of this work is to assess quantitatively the
      accuracy of prediction obtained with state-of-the-art data analysis techniques
      for BC microarray data through an independent and thorough framework. RESULTS:
      Due to the large number of variables, the reduced amount of samples and the high
      degree of noise, complex prediction methods are highly exposed to performance
      degradation despite the use of cross-validation techniques. Our analysis shows
      that the most complex methods are not significantly better than the simplest one,
      a univariate model relying on a single proliferation gene. This result suggests
      that proliferation might be the most relevant biological process for BC
      prognostication and that the loss of interpretability deriving from the use of
      overcomplex methods may be not sufficiently counterbalanced by an improvement of
      the quality of prediction. AVAILABILITY: The comparison study is implemented in
      an R package called survcomp and is available from
      http://www.ulb.ac.be/di/map/bhaibeka/software/survcomp/.

PMID- 18635568
TI  - Development of a two-dimensional agent-based model for chronic chagasic
      cardiomyopathy after stem cell transplantation.
AB  - MOTIVATION: A significant issue in stem cell therapy is to understand the role of
      this type of cell in the tissue regeneration. To explain this mechanism, an
      experimental study has quantified that the bone marrow cell transplantation
      decreases the number of inflammatory cells and reduces the fibrosis area in
      chagasic mice. Using this experimental data, we have developed an agent-based
      computational model to investigate the regeneration of the chronic chagasic
      cardiomyopathy after bone marrow stem cell transplantation. RESULTS: Our model
      includes six different types of agents: inflammatory cell, fibrosis area,
      cardiomyocyte, proinflammatory cytokine tumor necrosis factor-alpha, Trypanosoma
      cruzi parasite and bone marrow stem cell. This latter promotes apoptosis in
      inflammatory cells, reduction in the fibrosis area and can differentiate into
      cardiomyocyte. Proinflammatory cytokine tumor necrosis factor-alpha can increase
      the fibrosis area and T.cruzi can increase the number of inflammatory cells. Our
      results for both apoptosis of inflammatory cells and reduction in the fibrosis
      area were compared with experimental data. They suggest that the concentration
      pattern is the most important factor to characterize the kinetics of cardiac
      tissue regeneration after bone marrow stem cell transplantation. AVAILABILITY:
      The source code of our software is available online at
      www.vivas.ufba.br/bone/bone.zip .br Supplementaty information: Supplementary data
      are available at Bioinformatics online.

PMID- 18635569
TI  - Sircah: a tool for the detection and visualization of alternative transcripts.
AB  - Sircah is a flexible tool for the detection, analysis and visualization of
      alternative transcripts. It takes as input gene models or spliced alignments and
      creates a database of alternative transcription events: alternative transcription
      initiation and polyadenylation, alternative 3' and 5' splice-site usage, skipped
      exons and retained introns. The results can be visualized in a variety of ways,
      allowing the creation of publication quality images. AVAILABILITY: The Sircah is
      available for download under a creative commons license along with additional
      documentation and a tutorial from http://www.bork.embl.de/Sircah.

PMID- 18635570
TI  - mlegp: statistical analysis for computer models of biological systems using R.
AB  - Gaussian processes (GPs) are flexible statistical models commonly used for
      predicting output from complex computer codes. As such, GPs are well suited for
      the analysis of computer models of biological systems, which have been
      traditionally difficult to analyze due to their high-dimensional, non-linear and
      resource-intensive nature. We describe an R package, mlegp, that fits GPs to
      computer model outputs and performs sensitivity analysis to identify and
      characterize the effects of important model inputs. AVAILABILITY:
      http://www.biomath.org/mlegp

PMID- 18635571
TI  - MetalDetector: a web server for predicting metal-binding sites and disulfide
      bridges in proteins from sequence.
AB  - The web server MetalDetector classifies histidine residues in proteins into one
      of two states (free or metal bound) and cysteines into one of three states (free,
      metal bound or disulfide bridged). A decision tree integrates predictions from
      two previously developed methods (DISULFIND and Metal Ligand Predictor). Cross
      validated performance assessment indicates that our server predicts disulfide
      bonding state at 88.6% precision and 85.1% recall, while it identifies cysteines
      and histidines in transition metal-binding sites at 79.9% precision and 76.8%
      recall, and at 60.8% precision and 40.7% recall, respectively. AVAILABILITY:
      Freely available at http://metaldetector.dsi.unifi.it. SUPPLEMENTARY INFORMATION:
      Details and data can be found at http://metaldetector.dsi.unifi.it/help.php.

PMID- 18635572
TI  - The protein information and property explorer: an easy-to-use, rich-client web
      application for the management and functional analysis of proteomic data.
AB  - MOTIVATION: Mass spectrometry experiments in the field of proteomics produce
      lists containing tens to thousands of identified proteins. With the protein
      information and property explorer (PIPE), the biologist can acquire functional
      annotations for these proteins and explore the enrichment of the list, or
      fraction thereof, with respect to functional classes. These protein lists may be
      saved for access at a later time or different location. The PIPE is interoperable
      with the Firegoose and the Gaggle, permitting wide-ranging data exploration and
      analysis. The PIPE is a rich-client web application which uses AJAX capabilities
      provided by the Google Web Toolkit, and server-side data storage using Hibernate.
      AVAILABILITY: http://pipe.systemsbiology.net.

PMID- 18635573
TI  - MetaRoute: fast search for relevant metabolic routes for interactive network
      navigation and visualization.
AB  - We present MetaRoute, an efficient search algorithm based on atom mapping rules
      and path weighting schemes that returns relevant or textbook-like routes between
      a source and a product metabolite within seconds for genome-scale networks. Its
      speed allows the algorithm to be used interactively through a web interface to
      visualize relevant routes and local networks for one or multiple organisms based
      on data from KEGG. AVAILABILITY: http://www-bs.informatik.uni
      tuebingen.de/Services/MetaRoute. SUPPLEMENTARY INFORMATION: Supplementary details
      are available at http://www-bs.informatik.uni-tuebingen.de/Services/MetaRoute.

PMID- 18635574
TI  - Water disinfection by-products and pre-labor rupture of membranes.
AB  - The causes of term pre labor rupture of membranes (term PROM) remain poorly
      defined. The authors conducted a record-based prevalence study to explore a
      possible relation between disinfection by-products in drinking water and term
      PROM in an Australian community with spatially variable trihalomethane and
      nitrate levels. A multilevel statistical model was used to examine the relation
      between factors operating at the levels of the individual, district, and water
      distribution zone and the prevalence of PROM at term among 16,229 women in Perth,
      Western Australia (2002-2004). Adjusted odds ratios for term PROM increased with
      increasing tertiles of nitrate exposure (moderate exposure: odds ratio = 1.23,
      95% confidence interval: 1.03, 1.52; high exposure: odds ratio = 1.47, 95%
      confidence interval: 1.20, 1.79), but there was no significant relation with
      exposure to trihalomethanes. This study raises the possibility that water
      contaminants may promote the development of PROM at term.

PMID- 18635575
TI  - An augmented data method for the analysis of nosocomial infection data.
AB  - The analysis of nosocomial infection data for communicable pathogens is
      complicated by two facts. First, typical pathogens more commonly cause
      asymptomatic colonization than overt disease, so transmission can be only
      imperfectly observed through a sequence of surveillance swabs, which themselves
      have imperfect sensitivity. Any given set of swab results can therefore be
      consistent with many different patterns of transmission. Second, data are often
      highly dependent: the colonization status of one patient affects the risk for
      others, and, in some wards, repeated admissions are common. Here, the authors
      present a method for analyzing typical nosocomial infection data consisting of
      results from arbitrarily timed screening swabs that overcomes these problems and
      enables simultaneous estimation of transmission and importation parameters,
      duration of colonization, swab sensitivity, and ward- and patient-level
      covariates. The method accounts for dependencies by using a mechanistic
      stochastic transmission model, and it allows for uncertainty in the data by
      imputing the imperfectly observed colonization status of patients over repeated
      admissions. The approach uses a Markov chain Monte Carlo algorithm, allowing
      inference within a Bayesian framework. The method is applied to illustrative data
      from an interrupted time-series study of vancomycin-resistant enterococci
      transmission in a hematology ward.

PMID- 18635576
TI  - Pharmacological manipulation of gain-of-function and dominant-negative mechanisms
      in rhodopsin retinitis pigmentosa.
AB  - Mutations in the dim light photoreceptor protein rod opsin cause autosomal
      dominant retinitis pigmentosa. The majority of these mutations (class II) lead to
      protein misfolding. For example, the common class II rod opsin mutation P23H
      misfolds and is retained in the ER, prior to retrotranslocation and degradation
      by the proteasome. If degradation fails then the protein can aggregate to form
      intracellular inclusions. Furthermore, mutant opsin exerts a dominant negative
      effect on the wild-type (WT) protein. Here we show that the toxic gain of
      function and dominant negative properties of misfolded rod opsin in cells can be
      alleviated by drug treatments targeted against a range of cellular pathways. P23H
      rod opsin aggregation, inclusion formation with associated caspase activation and
      cell death were reduced by kosmotropes, molecular chaperone inducers and mToR
      inhibition. But these treatments did not enhance mutant opsin folding or reduce
      the dominant negative effect of P23H rod opsin. In contrast, retinoids acted as
      pharmacological chaperones to enhance P23H folding and reduce the dominant
      negative effect on WT rod opsin processing, as well as reducing toxic gains of
      function. Therefore, the suppression of the dominant negative effects of protein
      misfolding required enhanced folding of the mutant protein, whereas suppression
      of toxic gain of function effects did not require improved folding per se. These
      studies suggest that some forms of rhodopsin RP may be treated by targeting
      protein folding and reducing protein aggregation.

PMID- 18635577
TI  - The identification and characterization of a FOXL2 response element provides
      insights into the pathogenesis of mutant alleles.
AB  - The Forkhead transcription factor FOXL2 plays a crucial role in ovarian
      development and maintenance. In humans, its mutations lead to craniofacial
      abnormalities, isolated or associated with ovarian dysfunction. Using a
      combinatorial approach, we identified and characterized a FoxL2 response element
      (FLRE) and showed that it is highly specific and that it diverges from that of
      other Forkhead transcription factors. This specificity should prevent aberrant
      regulation of FOXL2 targets by other members of the family and should prevent
      ectopic activation of the ovarian differentiation program in testes. We provide
      evidence that the FLRE is used in naturally occurring promoters. We show that
      polyAlanine expansions of FOXL2, which are the most frequent pathogenic
      mutations, induce a length-dependent loss of response on different artificial
      promoter reporters depending on the number and sequence of the FLREs that they
      contain. Thus, we provide clear mechanistic evidence explaining how the
      architecture of promoters influences their sensitivity to decreased transcription
      factor availability. Furthermore, we speculate that the generally absent ovarian
      phenotype of patients carrying the most frequent polyAlanine expansion should
      come from its ability to properly regulate high-affinity ovarian targets. The
      existence of critical high-affinity ovarian targets would be compatible with the
      role of FOXL2 in reproduction and ensure developmental and functional robustness.
      Taken together, our results give mechanistic insights on the molecular
      pathogenesis of FOXL2 polyAlanine expansions.

PMID- 18635578
TI  - Dementia of the Alzheimer type.
AB  - Dementia of the Alzheimer type is a progressive, fatal neurodegenerative
      condition characterized by deterioration in cognition and memory, progressive
      impairment in the ability to carry out activities of daily living, and a number
      of neuropsychiatric symptoms. This narrative review summarizes the literature
      regarding descriptive epidemiology, clinical course, and characteristic
      neuropathological changes of dementia of the Alzheimer type. Although there are
      no definitive imaging or laboratory tests, except for brain biopsy, for
      diagnosis, brief screening instruments and neuropsychiatric test batteries used
      to assess the disease are discussed. Insufficient evidence exists for the use of
      biomarkers in clinical practice for diagnosis or disease management, but
      promising discoveries are summarized. Optimal treatment requires both
      nonpharmacological and pharmacological interventions, yet none have been shown to
      modify the disease's clinical course. This review describes the current available
      options and summarizes promising new avenues for treatment. Issues related to the
      care of persons with dementia of the Alzheimer type, including caregiver burden,
      long-term care, and the proliferation of dementia special care units, are
      discussed. Although advances have been made, more research is needed to address
      the gaps in our understanding of the disease.

PMID- 18635579
TI  - Phonological representations in deaf children: rethinking the "functional
      equivalence" hypothesis.
AB  - The sources of knowledge that individuals use to make similarity judgments
      between words are thought to tap underlying phonological representations. We
      examined the effects of perceptual similarity between stimuli on deaf children's
      ability to make judgments about the phonological similarity between words at 3
      levels of linguistic structure (syllable, rhyme, and phoneme). Manipulation of
      stimulus contrasts (acoustic, visual/orthographic, tactile/motoric) allowed a
      finer-grained estimate of the sources of knowledge that deaf individuals use to
      make similarity judgments between words. The results showed that the ability to
      make syllable-, rhyme-, and phoneme-level judgments was not tied to
      "phonological" facilitation when these conditions are contrasted. These findings
      are inconsistent with long-held assumptions of "functional" equivalence between
      "heard" and "seen" speech in the development of phonological representations in
      deaf learners. We argue that previous studies reporting evidence for phonological
      effects in similarity judgments have failed to sufficiently control for
      alternative sources of sensory information, namely, visual and tactile/motoric.

PMID- 18635580
TI  - Structure and functional analysis of wheat ICE (inducer of CBF expression) genes.
AB  - Two different inducers of CBF expression (ICE1-like genes), TaICE41 and TaICE87,
      were isolated from a cDNA library prepared from cold-treated wheat aerial
      tissues. TaICE41 encodes a protein of 381 aa with a predicted MW of 39.5 kDa
      while TaICE87 encodes a protein of 443 aa with a predicted MW of 46.5 kDa.
      TaICE41 and TaICE87 share 46% identity while they share 50 and 47% identity with
      Arabidopsis AtICE1 respectively. Expression analysis revealed that mRNA
      accumulation was not altered by cold treatment suggesting that both genes are
      expressed constitutively. Gel mobility shift analysis showed that TaICE41 and
      TaICE87 bind to different MYC elements in the wheat TaCBFIVd-B9 promoter.
      Transient expression assays in Nicotiana benthamiana, showed that both TaICE
      proteins can activate TaCBFIVd-B9 transcription. The different affinities of
      TaICE41 and TaICE87 for MYC variants suggest that ICE binding specificity may be
      involved in the differential expression of wheat CBF genes. Furthermore, analysis
      of MYC elements demonstrates that a specific variant is present in the wheat CBF
      group IV that is associated with freezing tolerance. Overexpression of either
      TaICE41 or TaICE87 genes in Arabidopsis enhanced freezing tolerance only upon
      cold acclimation suggesting that other factors induced by low temperature are
      required for their activity. The increased freezing tolerance in transgenic
      Arabidopsis is associated with a higher expression of the cold responsive
      activators AtCBF2, AtCBF3, and of several cold-regulated genes.

PMID- 18635581
TI  - ADAM10 is essential for proteolytic activation of Notch during thymocyte
      development.
AB  - Notch signaling pathway has been shown to play essential roles in T lymphocyte
      development. Activation of Notch requires a sequential proteolytic cleavage,
      which converts Notch from the full-length membrane-bound form to a
      transcriptionally active intracellular fragment. Studies in Drosophila showed
      that Kuzbanian (Kuz) is responsible for the enzymatic cleavage of extracellular
      S2 site upon Notch binding to its ligand Delta. Both a disintegrin and
      metalloprotease (ADAM) 10 and ADAM17, members of the ADAM family
      metalloproteases, have been indicated as the mammalian counterpart of Kuz in
      activating Notch in mammals. Here, we investigated functions of ADAM10 in Notch
      signaling during thymocyte development. We show that conditional disruption of
      the Adam10 gene in mouse thymocytes results in a developmental defect similar to
      the phenotypes previously described for T lineage-specific disruption of Notch1.
      We further show that the activation of Notch1 and its downstream target genes
      Deltex-1 and Pre-Ta are impaired in Adam10-deficient thymocytes. Our study
      demonstrates a T cell intrinsic role for Adam10 in activation of Notch1 during
      thymocyte development.

PMID- 18635582
TI  - Phenotypic classification of human CD4+ T cell subsets and their differentiation.
AB  - CD4(+) T cells have T(h) cell function and include two major functional subsets,
      T(h)1 and T(h)2. However, there are a restricted number of studies concerning
      phenotypic classification of human CD4(+) T cells. Here by using seven- and eight
      color flow cytometric analysis, we investigated the function of the subsets
      classified by four markers, CD27, CD28, CD45RA and CCR7. Five major subsets were
      identified by using these markers. These subsets showed different patterns of
      cytokine production after they were stimulated with phorbol myristate acetate and
      ionomycin. The analyses of cytokine production suggested that
      CCR7(+)CD45RA(+)CD27(+)CD28(+), CCR7(+)CD45RA(-)CD27(+)CD28(+) and CCR7(-)CD45RA(
      )CD27(+)CD28(+) subsets were naive, central memory and effector memory T cells,
      respectively, whereas CCR7(-)CD45RA(-)CD27(-)CD28(+) and CCR7(-)CD45RA(-)CD27(
      )CD28(-) subsets included T(h)1 and T(h)2 cells. The analysis of cytokine
      production by these subsets stimulated with anti-CD3 and anti-CD28 mAbs or with
      human cytomegalovirus antigens showed that IFN-gamma production was significantly
      higher in the CCR7(-)CD45RA(-)CD27(-)CD28(-) subset than in other subsets and
      that both CCR7(-)CD45RA(-)CD27(-)CD28(+) and CCR7(-)CD45RA(-)CD27(-)CD28(-)
      subsets produced a higher level of IL-4 than did other subsets. Our analyses
      demonstrated that the CCR7(-)CD45RA(-)CD27(-)CD28(-) subset predominantly
      included T(h)1 effector cells and that CCR7(-)CD45RA(-)CD27(-)CD28(+) subsets
      included T(h)1 and T(h)2 effector memory/effector cells as well as unclassified
      cells. The analysis of classification by using these four markers also suggested
      the differentiation pathway of human CD4(+) T cells.

PMID- 18635583
TI  - Rapid and safe establishment of cardiopulmonary bypass in repair of acute aortic
      dissection: improved results with double cannulation.
AB  - There is no agreement at present as to which is the optimal site for artery
      cannulation for cardiopulmonary bypass in repair of acute aortic dissection
      (AAD). We have employed right axillary artery cannulation (RAAC) in combination
      with femoral artery cannulation to overcome the drawbacks of single cannulation.
      From January 2000 to August 2006, 88 patients underwent emergency surgical repair
      of the aortic arch (mean age 65+/-13 years, 37 men) for AAD. All operations were
      performed under hypothermic circulatory arrest with antegrade selective cerebral
      perfusion. Preoperatively, nine patients were in shock and 18 patients showed
      malperfusion. The average duration of circulatory arrest was 52+/-17 min and that
      of myocardial ischemia was 135+/-53 min. Total aortic arch replacement was done
      in 47 patients and hemiarch aortic replacement in 41. The hospital mortality rate
      was 2.3% (2 of 88); the fatal cases were among those who were in shock
      preoperatively. The perioperative stroke rate was 5.7% (5 of 88). The hospital
      mortality rate of the 25 patients with preoperative malperfusion was 4.0% (1 of
      25); the fatal case had coronary malperfusion. Our approach for AAD was
      associated with a low mortality even in patients with malperfusion.

PMID- 18635584
TI  - Primary left atrial haemangioendothelioma.
AB  - We describe the case of a 21-year-old female patient with epithelioid
      haemangioendothelioma of the roof of the left atrium. The patient underwent
      radical resection of the tumour with large disease-free margins, which required
      reconstruction of left and right atrial superior walls. The prognosis is
      unpredictable, but life expectancies ranging from 1 to 20 years have been
      described. There is no single treatment that can be prescribed but, because of
      their biologic behaviour, epithelioid haemangioendotheliomas must be regarded as
      fully malignant neoplasms and ought to be resected radically to prevent
      metastatic disease, and to improve life expectancy and quality of life.

PMID- 18635585
TI  - The Haemonetics Cell Saver 5 washing properties: effect of different washing pump
      and centrifuge speeds.
AB  - This study evaluated the effect of different washing and centrifuge rates of the
      Cell Saver 5 on the quality of processed autologous blood. Autologous blood was
      washed with 1000 ml of sterile normal saline at centrifuge speed of 5650
      revolutions per minute (rpm) (group I) or 4350 rpm (group II) with different
      washing pump speeds--500, 800 and 1000 ml/min. Hemoglobin, free hemoglobin,
      hematocrit, erythrocytes, leukocytes, platelets, and protein were measured before
      and after processing. The highest values of hemoglobin, hematocrit and
      erythrocytes were achieved using 800 and 1000 ml/min pump speeds in group I and
      500 ml/min speed in group II. Red blood cells concentration was higher in group
      I. There were no significant changes of free hemoglobin removal within group I.
      In group II the lowest free hemoglobin was achieved when 1000 ml/min rate was
      used. Platelets and protein did not depend on wash pump speeds in both groups.
      Platelet recovery in group I was higher than in group II at all washing pump
      speeds. Leukocytes were not adequately removed at all pump speeds. The Cell Saver
      5 produces optimum results when the high wash pump speeds (800 and 1000 ml/min)
      and standard centrifuge speed are used.

PMID- 18635586
TI  - Treatments for tinnitus.
AB  - The various forms of treatment for tinnitus that have been tested in properly
      controlled trials can be classified as pharmacological, acoustic-physical, and
      psychological. In clinical trials, no pharmacological agent has been shown to
      have lasting effect on the presence or severity of tinnitus, although there are
      promising signs in an animal model. Acoustic devices do not seem to influence
      tinnitus, although appropriately fitted hearing aids may slightly reduce its
      prominence. Of physical treatments, cortical implantation may hold some promise
      of being effective for tinnitus suppression in selected cases. A psychological
      treatment that has emerged as consistently beneficial is cognitive-behavior
      therapy in terms of affecting overall well-being and reducing level of tinnitus
      annoyance.

PMID- 18635587
TI  - Patient perceptions of hospital discharge: reliability and validity of a Patient
      Continuity of Care Questionnaire.
AB  - BACKGROUND: Review of the literature reveals a need to develop a questionnaire
      that measures patient perceptions of factors impacting continuity of care
      following discharge from hospital. Such a measure has the potential to guide
      quality improvement initiatives related to continuity of care. OBJECTIVE: Our
      objective was to develop and examine the psychometric properties of a measure
      that would meet this need, the Patient Continuity of Care Questionnaire (PCCQ).
      METHOD: The PCCQ was administered to 204 inpatients 4 weeks after discharge. The
      questionnaire was assessed by item and principal components analysis. Factors
      derived from principal components analysis were assessed for internal consistency
      and construct validity. RESULTS: A principal components analysis resulted in six
      subscales including perceptions of: (1) relationships with providers in hospital,
      (2) information transfer to patients, (3) relationships with providers in
      community, (4) management of written forms, (5) management of follow-up and (6)
      management of communication among providers. These subscales were internally
      consistent in our sample and demonstrated construct validity through correlations
      with other related constructs. CONCLUSION: This initial study supports the
      reliability and validity of the PCCQ for measuring patient perceptions of factors
      central to continuity of care. The questionnaire subscales correspond to the
      theoretical components of continuity of care that have been proposed in the
      literature, namely informational, relational and management continuity. The
      subscales may be of value for identifying problems in continuity of care and for
      evaluating interventions aimed at improving continuity of care for patients after
      hospital discharge.

PMID- 18635588
TI  - Impact of miscommunication in medical dispute cases in Japan.
AB  - OBJECTIVE: Medical disputes between physicians and patients can occur in non
      negligent circumstances and may even result in compensation. We reviewed medical
      dispute cases to investigate the impact of miscommunication, especially in non
      negligent situations. DESIGN: Systematic review of medical dispute records was
      done to identify the presence of the adverse events, the type of medical error,
      preventability, the perception of miscommunication by patients and the amount of
      compensation. SETTING: The study was performed in Kyoto, Japan. PARTICIPANTS: We
      analyzed 155 medical dispute cases. MAIN OUTCOME MEASURES: We compared (i)
      frequency of miscommunication cases between negligent and non-negligent cases,
      and (ii) proportions of positive compensation between non-miscommunication and
      miscommunication cases stratified according to the existence of negligence.
      Multivariate logistic analysis was conducted to assess the independent factors
      related to positive compensation. RESULTS: Approximately 40% of the medical
      disputes (59/155) did not involve medical error (i.e. non-negligent). In the non
      negligent cases, 64.4% (38/59) involved miscommunication, whereas in dispute
      cases with errors, 21.9% (21/96) involved miscommunications. (P <thinsp;0.01)
      Although almost at negligent dispute cases were compensated (94/96), the
      frequency of positive compensation in non-negligent cases was significantly
      higher if miscommunication was perceived: 78.9% (30/38) with miscommunication and
      52.4% (11/21) with non-miscommunication (P < 0.05). The presence of medical error
      and patients' perception of miscommunication were important predictors of
      positive compensation (odds ratio: 36.9 and 3.6, respectively.) CONCLUSIONS:
      Medical disputes can occur without negligence and may have costly consequences.
      Medical staffs need to understand that not only the 'presence of medical errors',
      but also 'patients' perception of miscommunication', especially in cases with a
      non-negligent adverse event, can cause serious medical disputes. To prevent
      future disputes or claims, there is a strong need to improve communication
      between providers and patients or their relatives.

PMID- 18635589
TI  - Smoking: a deadly pleasant habit--is there a way out?
AB  - It was not until 1958 that the first major epidemiologic study demonstrated a
      strong correlation between smoking and cardiovascular disease. Although not
      providing definitive evidence that tobacco smoke was responsible for the
      increased coronary risk, it prompted the first anti-smoking measures by the US
      Surgeon General in his 1964 report. Smoking is a highly addictive (biological and
      psychological) habit. The severity of withdrawal symptoms that patients find
      distressing can be reduced by nicotine replacement therapy. Bupropion SR was the
      first nonnicotine medication shown to be effective for smoking cessation. Its
      possible mechanisms of action include blockade of neuronal reuptake of dopamine
      and norepinephrine and blockade of nicotinic acetylcholinergic receptors.
      Varenicline, a nicotine receptor partial agonist, is the most recently developed
      nonnicotine preparation. The odds of smoking cessation after 12 weeks of 1 mg
      twice-daily varenicline treatment was approximately twice that achieved with 150
      mg twice-daily bupropion and nearly 4-fold greater than with placebo.

PMID- 18635590
TI  - Modification of cardiometabolic risk through cannabinoid type-1 receptor
      antagonism.
AB  - Large-scale epidemiological studies show that hypertension, diabetes, and
      dyslipidaemia are highly prevalent among obese individuals. Regrettably,
      preventive efforts have failed to abolish the increasing prevalence of obesity
      worldwide. The endocannabinoid system is implicated in the regulation of
      appetite, food intake, lipids, and glucose metabolism. Rimonabant is the first
      type-1 endocannabinoid receptor blocker that has been shown to improve the serum
      lipid profile, insulin and glucose levels, and blood pressure. In particular, the
      RIO (rimonabant in obesity) studies documented the beneficial metabolic effects
      of rimonabant. These favorable metabolic effects exceed by about 50% those
      anticipated by weight reduction, possibly due to modulation of the
      endocannabinoid system in peripheral tissues. The beneficial effects, however,
      seem to come at the cost of an increased risk of psychiatric disorders. However,
      given the efficacy of this treatment and the magnitude of the obesity problem,
      rimonabant may prove to be a valuable adjunct in targeting obesity-related
      cardiovascular risk factors.

PMID- 18635592
TI  - Going out on a limb: prosthetics, normalcy and disputing the therapy/enhancement
      distinction.

PMID- 18635593
TI  - Biosynthesis, remodelling and functions of mammalian GPI-anchored proteins:
      recent progress.
AB  - More than 100 mammalian proteins are post-translationally modified by
      glycosylphosphatidylinositol (GPI) at their C-termini and are anchored to the
      cell surface membrane via the lipid portion. GPI-anchored proteins (GPI-APs) have
      various functions, such as hydrolytic enzymes, receptors, adhesion molecules,
      complement regulatory proteins and other immunologically important proteins. GPI
      anchored proteins are mainly associated with membrane microdomains or membrane
      rafts enriched in sphingolipids and cholesterol. It is thought that association
      with membrane rafts is important for GPI-APs in signal transduction and other
      functions. Here, we review recent progress in studies on biosynthesis,
      remodelling and functions of mammalian GPI-APs.

PMID- 18635594
TI  - Multiple antibody reactivities to citrullinated antigens in sera from patients
      with rheumatoid arthritis: association with HLA-DRB1 alleles.
AB  - BACKGROUND: Autoantibodies to cyclic citrullinated peptides (anti-CCP) are
      present in most patients with rheumatoid arthritis (RA), and associate with HLA
      DRB1 shared epitope (SE) alleles. OBJECTIVE: To investigate reactivities of anti
      CCP to various citrullinated proteins/peptides, which represent potential
      autoantigens in RA, and to examine the relationship between such antibodies, and
      their association with genetic variants within HLA-DRB1 SE alleles. METHODS:
      Serum samples from 291 patients with established RA and 100 sex- and age-matched
      healthy subjects were included in this study. Sera were first analysed for
      presence of anti-CCP antibodies and further for IgG and IgA antibodies towards
      candidate autoantigens in both their native and citrullinated form including:
      fibrinogen, alpha-enolase peptide-1 and the C1-epitope of type II collagen
      (C1(III)). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR
      genotyping was performed. RESULTS: 72% of patients with RA were anti-CCP
      positive. Among the candidate autoantigens examined, IgG antibodies to
      citrullinated fibrinogen were found in 66% of patients' sera and in 41% for both
      citrullinated alpha-enolase peptide-1 and citrullinated C1(III). These antibodies
      were mainly seen in the anti-CCP-positive patient group; they were specific for
      their respective antigen and displayed limited cross reactivity. IgA responses
      were also detected, but less frequently than IgG. Anti-CCP and anti-citrullinated
      protein antibodies were associated with HLA-DRB1*04 rather than with HLA-DRB1*01
      alleles. CONCLUSIONS: Antibodies directed against several citrullinated antigens
      are present in CCP-positive RA, with many patients displaying multireactivity.
      All specific reactivities were primarily associated with the HLA-DRB1*04 alleles,
      suggesting common pathways of anti-citrulline immunity.

PMID- 18635595
TI  - Dissecting the contribution of innate and antigen-specific pathways to the breach
      of self-tolerance observed in a murine model of arthritis.
AB  - BACKGROUND: The relative roles of innate immunity and antigen-specific T cells in
      rheumatoid arthritis remain controversial. Previous studies demonstrated that T
      helper type 1 cells of irrelevant antigen specificity (ovalbumin) induced a
      transient arthritis in BALB/c mice, which recapitulates many of the pre-articular
      and articular features of human disease and is associated with the emergence of
      autoreactive T and B-cell responses to joint-specific antigens. However, the
      mechanisms underlying this phenomenon were unclear. OBJECTIVES: The aim of this
      study was to dissect the relative contribution of innate and heterologous antigen
      specific pathways to the breach of self-tolerance and pathology observed in this
      model and how this may result from modified T and B-cell interactions. METHODS:
      To address this issue, experimental arthritis was elicited either by a non
      specific inflammatory stimulus alone, by activation of T cells of an irrelevant
      specificity or a combination of both. RESULTS: The non-specific inflammatory
      response generated by lipopolysaccharide led to articular inflammation and
      cartilage erosion, but did not break tolerance to joint-specific antigens. In
      contrast, local activation of T cells of an irrelevant specificity produced a
      similar pathological picture but, in addition, induced T-cell responses to
      unrelated joint-specific antigens with associated activation of autoreactive B
      cells. These effects could be further potentiated by the addition of
      lipopolysaccharide. CONCLUSION: These data demonstrate that non-specific
      inflammation alone is insufficient to breach self-tolerance. In contrast, T cells
      of an irrelevant specificity, when triggered locally in an antigen-specific
      manner, can breach self-tolerance leading to arthritis and autoantibody
      production, which can then be amplified in a non-specific manner.

PMID- 18635596
TI  - Anti-inflammatory therapy with tumour necrosis factor alpha inhibitors improves
      high-density lipoprotein cholesterol antioxidative capacity in rheumatoid
      arthritis patients.
AB  - OBJECTIVE: High-density lipoprotein (HDL) antiatherogenic functions seem to be
      diminished during inflammatory conditions such as rheumatoid arthritis (RA). The
      aim of this study was to investigate the effects of tumour necrosis factor (TNF)
      inhibition on the antioxidative capacity of HDL in RA. METHODS: Plasma lipids and
      paraoxonase (PON-1) activity were investigated in 45 RA patients, before and
      during 6 months of anti-TNF therapy. In addition, HDL was isolated and tested for
      its ability to inhibit copper-induced oxidation of low-density lipoprotein in
      vitro. RESULTS: Plasma HDL concentrations did not change considerably after 6
      months of therapy. However, stable increases of PON-1 activities were observed
      throughout the same period (p<0.03). The increases were more obvious when related
      to HDL or apolipoprotein AI concentrations. HDL total antioxidative capacity
      significantly improved 6 months after the initiation of anti-TNF therapy (p =
      0.015). The initial improvement of PON-1 activity paralleled a decrease in the
      inflammatory status, whereas specific TNF blockade was likely to be responsible
      for the long-term effects. CONCLUSIONS: Anti-TNF therapy with infliximab has
      beneficial effects on lipids through changes in HDL antioxidative capacity, which
      might be clinically relevant and contribute to the reported protective effect of
      anti-TNF on cardiovascular morbidity in RA. This emphasises the importance of HDL
      antiatherogenic capacity for cardiovascular risk in chronic inflammatory
      conditions.

PMID- 18635597
TI  - Costs and quality of life of patients with ankylosing spondylitis in Hong Kong.
AB  - OBJECTIVES: To assess the annual direct, indirect and total societal costs,
      quality of life (QoL) of AS in a Chinese population in Hong Kong and determine
      the cost determinants. METHODS: A retrospective, non-randomized, cross-sectional
      study was performed in a cohort of 145 patients with AS in Hong Kong.
      Participants completed questionnaires on sociodemographics, work status and out
      of-pocket expenses. Health resources consumption was recorded by chart review.
      Functional impairment and disease activity were measured using the Bath
      Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), respectively. Patients' QoL was
      assessed using the Short Form-36 (SF-36). RESULTS: The mean age of the patients
      was 40 yrs with mean disease duration of 10 yrs. The mean BASDAI score was 4.7
      and BASFI score was 3.3. Annual total costs averaged USD 9120. Direct costs
      accounted for 38% of the total costs while indirect costs accounted for 62%.
      Costs of technical examinations represented the largest proportion of total cost.
      Patients with AS reported significantly impaired QoL. Functional impairment
      became the major cost driver of direct costs and total costs. CONCLUSION: There
      is a substantial societal cost related to the treatment of AS in Hong Kong.
      Functional impairment is the most important cost driver. Treatments that reduce
      functional impairment may be effective to decrease the costs of AS and improve
      the patient's QoL, and ease the pressure on the healthcare system.

PMID- 18635598
TI  - A role for the integrin alpha6beta1 in the differential distribution of CD4 and
      CD8 T-cell subsets within the rheumatoid synovium.
AB  - OBJECTIVE: CD4 and CD8 T-cell subsets accumulate in distinct microdomains within
      the inflamed rheumatoid synovium. The molecular basis for their differential
      distribution remains unclear. Since chemokines and adhesion molecules play an
      important role in the positioning of leucocytes at sites of inflammation, we
      tested the hypothesis that the differential expression and function of chemokine
      and/or adhesion molecules explains why CD4(+) T cells accumulate within
      perivascular cuffs, whereas CD8(+) T cells distribute diffusely within the
      tissue. METHODS: Expression of an extensive panel of chemokine receptors and
      adhesion molecules on matched CD4(+) and CD8(+) T cells from peripheral blood
      (PB) and synovial fluid (SF) was analysed by multicolour flow cytometry.
      Migration assays and flow-based adhesion assays were used to assess the
      functional consequences of any differences in the expression of chemokine and
      adhesion receptors. RESULTS: CD4(+) and CD8(+) T cells from PB and SF expressed
      unique yet consistent patterns of chemokine and adhesion receptors. SF CD8(+) T
      cells were much less promiscuous in their expression of chemokine receptors than
      SF CD4(+) T cells. The alpha(6)beta(1) integrin was highly expressed on PB CD4(+)
      T cells, but not on PB CD8(+) T cells. Laminin, the ligand for alpha(6)beta(1),
      retained CD4(+) T cells, but less so CD8(+) T cells, within inflamed synovial
      tissue. CONCLUSION: Infiltrating PB CD4(+) T cells, but not CD8(+) T cells,
      express functional levels of the alpha(6)beta(1) integrin. We propose that this
      leads to their retention within the rheumatoid synovium in perivascular cuffs,
      which are defined and delineated by the expression of laminin.

PMID- 18635599
TI  - Interferon-gamma inhibits enterocyte migration by reversibly displacing
      connexin43 from lipid rafts.
AB  - Necrotizing enterocolitis (NEC) is associated with the release of interferon
      gamma (IFN) by enterocytes and delayed intestinal restitution. Our laboratory has
      recently demonstrated that IFN inhibits enterocyte migration by impairing
      enterocyte gap junctions, intercellular channels that are composed of connexin43
      (Cx43) monomers and that are required for enterocyte migration to occur. The
      mechanisms by which IFN inhibits gap junctions are incompletely understood. Lipid
      rafts are cholesterol-sphingolipid-rich microdomains of the plasma membrane that
      play a central role in the trafficking and signaling of various proteins. We now
      hypothesize that Cx43 is present on enterocyte lipid rafts and that IFN inhibits
      enterocyte migration by displacing Cx43 from lipid rafts in enterocytes. We now
      confirm our previous observations that intestinal restitution is impaired in NEC
      and demonstrate that Cx43 is present on lipid rafts in IEC-6 enterocytes. We show
      that lipid rafts are required for enterocyte migration, that IFN displaces Cx43
      from lipid rafts, and that the phorbol ester phorbol 12-myristate 13-acetate
      (PMA) restores Cx43 to lipid rafts after treatment with IFN in a protein kinase C
      dependent manner. IFN also reversibly decreased the phosphorylation of Cx43 on
      lipid rafts, which was restored by PMA. Strikingly, restoration of Cx43 to lipid
      rafts by PMA or by transfection of enterocytes with adenoviruses expressing wild
      type Cx43 but not mutant Cx43 is associated with the restoration of enterocyte
      migration after IFN treatment. Taken together, these findings suggest an
      important role for lipid raft-Cx43 interactions in the regulation of enterocyte
      migration during exposure to IFN, such as NEC.

PMID- 18635600
TI  - Role of MutS homolog 2 (MSH2) in intestinal myofibroblast proliferation during
      Crohn's disease stricture formation.
AB  - Tissue remodeling and mesenchymal cell accumulation accompanies chronic
      inflammatory disorders involving joints, lung, vasculature, and bowel. Chronic
      inflammation may alter DNA-mismatch repair (MMR) systems in mesenchymal cells,
      but is not defined in Crohn's disease (CD) and its associated intestinal
      remodeling and stricture formation. We determined whether DNA-MMR alteration
      plays a role in the pathogenesis of CD tissue remodeling. Control and CD bowel
      tissues were used to generate primary cultures of muscularis mucosa
      myofibroblasts, which were assessed directly or following stimulation with TNF
      alpha/LPS or H2O2. MutS homolog (MSH)2, MSH3, and MSH6 expression in tissues and
      myofibroblasts was determined. Immunohistochemical staining revealed an increased
      expression of MSH2 in CD muscularis mucosa and submucosal tissues compared with
      controls or uninvolved CD tissue, and MSH2 expression was increased in CD
      myofibroblasts compared with control cells. TNF-alpha/LPS and H2O2 further
      enhanced MSH2 expression in both control and CD cells, which were decreased by
      simvastatin. There were no significant changes in MSH3 and MSH6 expression.
      Proliferating cell nuclear antigen and Ki67 staining of CD tissue revealed
      increased proliferation in the muscularis mucosa and submucosa of chronically
      inflamed tissues, and enhanced proliferation was seen in CD myofibroblasts
      compared with controls. Simvastatin reversed the effects of inflammatory stress
      on the DNA-MMR and inhibited proliferation of control and CD myofibroblasts. Gene
      silencing with MSH2 siRNA selectively decreased CD myofibroblast proliferation.
      These data demonstrate a potential role for MSH2 in the pathogenesis of
      nonneoplastic mesenchymal cell accumulation and intestinal remodeling in CD
      chronic inflammation.

PMID- 18635601
TI  - PIN/LC8 is associated with cytosolic but not membrane-bound nNOS in the nitrergic
      varicosities of mice gut: implications for nitrergic neurotransmission.
AB  - This investigation demonstrates the presence and binding of the protein LC8
      (described as "protein inhibitor of nNOS" or PIN in some reports) to different
      components of neuronal nitric oxide synthase (nNOS) in nitrergic varicosities of
      mice gut. Whole varicosity extracts showed three (320-, 250-, and 155-kDa) nNOS
      bands with anti-nNOS(1422-1433) antibody and a 10-kDa band with anti-LC8
      antibody. The LC8 immunoprecipitate (IP) showed three nNOS bands, suggesting that
      LC8 was bound with all three forms of nNOS but dissociated from them during SDS
      PAGE. Studies using LC8 IP and supernatant and probed with anti-CaM showed that
      LC8 was not associated with CaM-bound 320-kDa nNOS but was present in the CaM
      lacking fraction. Probing these fractions with anti-serine847-P-nNOS showed that
      320-kDa serine847-phosphorylated-nNOS consisted of LC8-bound and LC8-lacking
      components. Subsequent studies with varicosity membrane and cytosolic fractions
      separately showed that membrane contained CaM-bound and CaM-lacking, serine847
      phosphorylated 320-kDa nNOS; both these fractions lacked LC8. On the other hand,
      the cytosolic fraction contained CaM-lacking, serine847-phosphorylated 320-kDa,
      250-kDa, and 155-kDa nNOS bands that were all associated with LC8. These studies,
      along with in vitro nitric oxide assays, show that in gut nitrergic nerve
      varicosities 1) all cytosolic serine847-phosphorylated nNOS was catalytically
      inactive and bound with LC8, and 2) membrane-associated nNOS consisted of
      catalytically active, CaM-bound and catalytically inactive, CaM-lacking,
      serine847-phosphorylated nNOSalpha dimers, both of which lacked LC8. These
      results suggest that LC8 may dissociate from the 320-kDa nNOSalpha dimer upon
      binding to membrane, thus supporting the view that LC8 may transport nNOSalpha
      dimer to the varicosity membrane for participation in nitrergic
      neurotransmission.

PMID- 18635602
TI  - Chronic peripheral administration of corticotropin-releasing factor causes
      colonic barrier dysfunction similar to psychological stress.
AB  - Chronic psychological stress causes intestinal barrier dysfunction and impairs
      host defense mechanisms mediated by corticotrophin-releasing factor (CRF) and
      mast cells; however, the exact pathways involved are unclear. Here we
      investigated the effect of chronic CRF administration on colonic permeability and
      ion transport functions in rats and the role of mast cells in maintaining the
      abnormalities. CRF was delivered over 12 days via osmotic minipumps implanted
      subcutaneously in wild-type (+/+) and mast cell-deficient (Ws/Ws) rats. Colonic
      segments were excised for ex vivo functional studies in Ussing chambers [short
      circuit current (Isc), conductance (G), and macromolecular permeability
      (horseradish peroxidase flux)], and analysis of morphological changes (mast cell
      numbers and bacterial host-interactions) was determined by light and electron
      microscopy. Chronic CRF treatment resulted in colonic mucosal dysfunction with
      increased Isc, G, and horseradish peroxidase flux in+/+but not in Ws/Ws rats.
      Furthermore, CRF administration caused mast cell hyperplasia and abnormal
      bacterial attachment and/or penetration into the mucosa only in+/+rats. Finally,
      selective CRF agonist/antagonist studies revealed that stimulation of CRF-R1 and
      CRF-R2 receptors induced the elevated secretory state and permeability
      dysfunction, respectively. Chronic CRF causes colonic barrier dysfunction in
      rats, which is mediated, at least in part, via mast cells. This information may
      be useful in designing novel treatment strategies for stress-related
      gastrointestinal disorders.

PMID- 18635604
TI  - Health Canada's investment in new post-market drug surveillance network a
      "pittance".

PMID- 18635603
TI  - Expression and hepatobiliary transport characteristics of the concentrative and
      equilibrative nucleoside transporters in sandwich-cultured human hepatocytes.
AB  - We previously reported that both the concentrative (hCNT) and equilibrative
      (hENT) nucleoside transporters are expressed in the human liver (21). Here we
      report a study that investigated the expression of these transporters
      (transcripts and proteins) and their role in the hepatobiliary transport of
      nucleosides/nucleoside drugs using sandwich-cultured human hepatocytes. In the
      hepatic tissue, the rank order of the mRNA expression of the transporters was
      hCNT1 approximately hENT1>hENT2 approximately hCNT2>hCNT3. In sandwich-cultured
      hepatocytes, the mRNA expression of hCNT2 and hENT2 was comparable to that in
      hepatic tissue, whereas the expression of corresponding transporters in the two
      dimensional hepatocyte cultures was lower. Colocalization studies demonstrated
      predominant localization of these transporters at the sinusoidal membrane and of
      hENT1, hCNT1, and hCNT2 at the canalicular membrane. In the sandwich-cultured
      hepatocytes, ENTs were the major contributors to the transport of thymidine
      (hENT1, 63%; hENT2, 23%) or guanosine (hENT1, 53%; hENT2, 24%) into the
      hepatocytes followed by hCNT1 (10%) for thymidine or hCNT2 (23%) for guanosine.
      Although ribavirin was predominately transported (89%) into the hepatocytes by
      hENT1, fialuridine (FIAU) was transported by both hENT1 (30%) and hCNTs (61%).
      The extensively metabolized natural nucleosides were not effluxed into the bile,
      whereas significant biliary-efflux was observed of FIAU (19%), ribavirin (30%),
      and formycin B (35%). We conclude that the hepatic activity of hENT1 and hCNT1/2
      transporters will determine the in vivo hepatic distribution and therefore the
      efficacy and/or toxicity of nucleoside drugs used to treat hepatic diseases.

PMID- 18635605
TI  - Neuro-cognitive performance in children with type 1 diabetes--a meta-analysis.
AB  - OBJECTIVE: To conduct meta-analyses of neuropsychological performance in young
      people with type 1 diabetes. METHODS: Meta-analysis of 24 studies. Studies
      published between 1980 and 2005 were identified. The inclusion criteria were:
      young people who were < or =19 years of age with type 1 diabetes, a case-control
      design and standardized neuropsychological tests of seven cognitive domains.
      RESULTS: Diabetes was statistically associated with poorer performance on
      visuospatial ability (d = -0.29), motor speed (d = -0.26) and writing (d = 
      0.28), on sustained attention (d = -0.21) and reading (d = -0.23). Smaller
      effects were identified on full IQ (d = -0.14), on performance (d = -0.18) and
      verbal IQ (d = -0.15). Severe hypoglycemia was linked to deficits in short-term
      verbal memory (d = -0.14; Confidence Interval: -0.318, 0.024; p =.04).
      CONCLUSIONS: This meta-analysis indicates that children with type 1 diabetes have
      mild cognitive impairments and subtly reduced overall intellectual functioning.

PMID- 18635606
TI  - Crucial role of vHNF1 in vertebrate hepatic specification.
AB  - Mouse liver induction occurs via the acquisition of ventral endoderm competence
      to respond to inductive signals from adjacent mesoderm, followed by hepatic
      specification. Little is known about the regulatory circuit involved in these
      processes. Through the analysis of vHnf1 (Hnf1b)-deficient embryos, generated by
      tetraploid embryo complementation, we demonstrate that lack of vHNF1 leads to
      defective hepatic bud formation and abnormal gut regionalization. Thickening of
      the ventral hepatic endoderm and expression of known hepatic genes do not occur.
      At earlier stages, hepatic specification of vHnf1-/- ventral endoderm is
      disrupted. More importantly, mutant ventral endoderm cultured in vitro loses its
      responsiveness to inductive FGF signals and fails to induce the hepatic
      specification genes albumin and transthyretin. Analysis of liver induction in
      zebrafish indicates a conserved role of vHNF1 in vertebrates. Our results reveal
      the crucial role of vHNF1 at the earliest steps of liver induction: the
      acquisition of endoderm competence and the hepatic specification.

PMID- 18635607
TI  - Origin and shaping of the laterality organ in zebrafish.
AB  - Handedness of the vertebrate body plan critically depends on transient embryonic
      structures/organs that generate cilia-dependent leftward fluid flow within
      constrained extracellular environments. Although the function of ciliated organs
      in laterality determination has been extensively studied, how they are formed
      during embryogenesis is still poorly understood. Here we show that Kupffer's
      vesicle (KV), the zebrafish organ of laterality, arises from a surface epithelium
      previously thought to adopt exclusively extra-embryonic fates. Live multi-photon
      confocal imaging reveals that surface epithelial cells undergo Nodal/TGFbeta
      signalling-dependent ingression at the dorsal germ ring margin prior to
      gastrulation, to give rise to dorsal forerunner cells (DFCs), the precursors of
      KV. DFCs then migrate attached to the overlying surface epithelium and rearrange
      into rosette-like epithelial structures at the end of gastrulation. During early
      somitogenesis, these epithelial rosettes coalesce into a single rosette that
      differentiates into the KV with a ciliated lumen at its apical centre. Our
      results provide novel insights into the morphogenetic transformations that shape
      the laterality organ in zebrafish and suggest a conserved progenitor role of the
      surface epithelium during laterality organ formation in vertebrates.

PMID- 18635608
TI  - Tissue-specific requirements of beta-catenin in external genitalia development.
AB  - External genitalia are body appendages specialized for internal fertilization.
      Their development can be divided into two phases, an early androgen-independent
      phase and a late androgen-dependent sexual differentiation phase. In the early
      phase, the embryonic anlage of external genitalia, the genital tubercle (GT), is
      morphologically identical in both sexes. Although congenital external genitalia
      malformations represent the second most common birth defect in humans, the
      genetic pathways governing early external genitalia development and urethra
      formation are poorly understood. Proper development of the GT requires
      coordinated outgrowth of the mesodermally derived mesenchyme and extension of the
      endodermal urethra within an ectodermal epithelial capsule. Here, we demonstrate
      that beta-catenin plays indispensable and distinct roles in each of the
      aforementioned three tissue layers in early androgen-independent GT development.
      WNT-beta-catenin signaling is required in the endodermal urethra to activate and
      maintain Fgf8 expression and direct GT outgrowth, as well as to maintain
      homeostasis of the urethra. Moreover, beta-catenin is required in the mesenchyme
      to promote cell proliferation. By contrast, beta-catenin is required in the
      ectoderm to maintain tissue integrity, possibly through cell-cell adhesion during
      GT outgrowth. The fact that both endodermal and ectodermal beta-catenin knockout
      animals develop severe hypospadias in both sexes raises the possibility that the
      deregulation of any of these functions can contribute to the etiology of
      congenital external genital defects in humans.

PMID- 18635609
TI  - BMP2 and BMP7 play antagonistic roles in feather induction.
AB  - Feathers, like hairs, first appear as primordia consisting of an epidermal
      placode associated with a dermal condensation that is necessary for the
      continuation of their differentiation. Previously, the BMPs have been proposed to
      inhibit skin appendage formation. We show that the function of specific BMPs
      during feather development is more complex. BMP2 and BMP7, which are expressed in
      both the epidermis and the dermis, are involved in an antagonistic fashion in
      regulating the formation of dermal condensations, and thus are both necessary for
      subsequent feather morphogenesis. BMP7 is expressed earlier and functions as a
      chemoattractant that recruits cells into the condensation, whereas BMP2 is
      expressed later, and leads to an arrest of cell migration, likely via its
      modulation of the EIIIA fibronectin domain and alpha4 integrin expression. Based
      on the observed cell proliferation, chemotaxis and the timing of BMP2 and BMP7
      expression, we propose a mathematical model, a reaction-diffusion system, which
      not only simulates feather patterning, but which also can account for the
      negative effects of excess BMP2 or BMP7 on feather formation.

PMID- 18635610
TI  - Conditional ablation of Notch signaling in pancreatic development.
AB  - The role of the Notch signaling members Notch1, Notch2 and Rbpj in exocrine
      pancreatic development is not well defined. We therefore analyzed conditional
      pancreas-specific Rbpj and combined Notch1/Notch2 knockout mice using
      Ptf1a(+/Cre(ex1)) mice crossed with floxed Rbpj or Notch1/Notch2 mice. Mice were
      analyzed at different embryonic stages for pancreatic exocrine and endocrine
      development. The absence of Rbpj in pancreatic progenitor cells impaired exocrine
      pancreas development up to embryonic day 18.5 and led to premature
      differentiation of pancreatic progenitors into endocrine cells. In Rbpj-deficient
      pancreata, amylase-expressing acini and islets formed during late embryonic and
      postnatal development, suggesting an essential role of Rbpj in early but not late
      development. Contrary to this severe phenotype, the concomitant inactivation of
      Notch1 and Notch2 only moderately disturbed the proliferation of pancreatic
      epithelial cells during early embryonic development, and did not inhibit
      pancreatic development. Our results show that, in contrast to Rbpj, Notch1 and
      Notch2 are not essential for pancreatogenesis. These data favor a Notch
      independent role of Rbpj in the development of the exocrine pancreas.
      Furthermore, our findings suggest that in late stages of pancreatic development
      exocrine cell differentiation and maintenance are independent of Rbpj.

PMID- 18635612
TI  - Origin of synchronized low-frequency blood oxygen level-dependent fluctuations in
      the primary visual cortex.
AB  - BACKGROUND AND PURPOSE: Low-frequency (<0.08 Hz) fluctuations in spontaneous
      blood oxygen level-dependent (BOLD) signal intensity show synchronization across
      anatomically interconnected and functionally specific brain regions, suggesting a
      neural origin of fluctuations. To determine the mechanism by which high-frequency
      neural activity results in low-frequency BOLD fluctuations, I obtained
      measurements of the effects of neurovascular coupling on the frequency content of
      BOLD fluctuations. MATERIALS AND METHODS: 3T recordings of BOLD signal intensity
      in the primary visual cortex were obtained in response to visual stimuli
      presented at varying temporal frequencies to determine which stimulus frequencies
      were successfully transmitted to BOLD signal intensity. Additional BOLD time
      series recordings were performed in a resting state and during natural visual
      stimulation, and frequencies comprising BOLD fluctuations were measured.
      Magnetoencephalographic (MEG) time series recordings were obtained in a resting
      state to measure which components of MEG signal intensity best correlated in
      frequency distribution to observed BOLD fluctuations. RESULTS: Visually driven
      oscillations in BOLD signal intensity were observed up to 0.2 Hz, representing a
      mismatch between low-pass filter properties of neurovascular coupling and
      observed frequencies of spontaneous BOLD fluctuations, which are <0.05 Hz in the
      primary visual cortex. Visual stimulation frequencies of >0.2 Hz resulted in
      frequency-dependent increases in mean BOLD response. Amplitude modulation of high
      frequency neural activity was measured in MEG time series data, which
      demonstrated 1/frequency distribution with the greatest power comprising
      frequencies <0.05 Hz, consistent with the distribution of observed BOLD
      fluctuations. CONCLUSION: Synchronized low-frequency BOLD fluctuations likely
      arise from a combination of vascular low-pass filtering and low-frequency
      amplitude modulation of neural activity.

PMID- 18635611
TI  - Cell-type-specific transcription of prospero is controlled by combinatorial
      signaling in the Drosophila eye.
AB  - In Drosophila, Notch and Egfr signaling regulate the determination of many cell
      types, and yet how these common signals generate cell-specific transcription is
      not well understood. In the compound eye, prospero (pros) is transcribed
      specifically in R7 photoreceptors and cone cells. We show that the transcription
      of pros is activated by two visual-specific transcription selectors, Glass and
      Sine Oculis, that bind to an enhancer and promote its activation. Together with
      the pre-patterning transcription factor Lozenge, these factors work in a highly
      combinatorial manner, such that cells missing any one factor transcribe pros only
      weakly, if at all. However, the factors are not sufficient to activate the
      enhancer because of an additional requirement for both Notch and Egfr signals.
      The loss of Notch signaling produces a ;salt and pepper' effect, with some cells
      expressing near-normal levels and others expressing no detectable pros at all;
      thus, the signaling loss does not produce a uniformly reduced level of
      transcription activity in cells. This suggests a probabilistic mechanism, in
      which Notch signals influence the likelihood that the enhancer is inactive or
      fully active in any given cell. The activity level, therefore, is dictated by the
      proper combination of highly cooperative selector and pre-pattern factors present
      in the cell.

PMID- 18635613
TI  - Endovascular treatment of peripheral aneurysms of the posterior inferior
      cerebellar artery.
AB  - BACKGROUND AND PURPOSE: Peripheral aneurysms of the posterior inferior cerebellar
      artery (PICA) are rare, and pre-existing literature concerning their endovascular
      treatment is limited. The purpose of this study was to assess the etiology and
      clinical characteristics of peripheral PICA aneurysms and to evaluate the
      angiographic and clinical results of the patients who underwent endovascular
      treatment for a peripheral PICA aneurysm in a single center. MATERIALS AND
      METHODS: Twelve consecutive patients with 12 peripheral PICA aneurysms (10
      ruptured) included in an internal data base were retrospectively reviewed.
      Posttreatment and follow-up angiograms were analyzed, and the clinical outcome
      was recorded. RESULTS: The etiology was dissection in 7 (58%) and unknown in 5
      cases (42%). Three dissecting aneurysms reruptured before endovascular treatment,
      and another 3 demonstrated angiographic progress. Four aneurysms were treated by
      endosaccular coiling, 6 (all dissecting) by parent artery occlusion, and in 2
      cases endovascular treatment failed. Angiographic outcome was complete aneurysm
      and/or parent artery occlusion in 9 cases and neck remnant in 1 case. One
      aneurysm needed retreatment at follow-up. One lethal procedural complication
      occurred, and transient ischemic symptoms appeared in 2 patients. The clinical
      outcome was good in 7 patients, whereas 3 patients, all poor clinical grade, died
      (1 for unrelated reasons). No rebleedings have occurred during the follow-up.
      CONCLUSION: In this series, most peripheral PICA aneurysms were secondary to
      arterial dissection. They were unstable with a high risk of rebleeding and a high
      mortality if not treated without delay. Endovascular treatment was effective in
      preventing rehemorrhage.

PMID- 18635614
TI  - MR imaging of familial Creutzfeldt-Jakob disease: a blinded and controlled study.
AB  - BACKGROUND AND PURPOSE: The E200K mutation of the PRNP (prion protein) gene is
      the most common cause of familial Creutzfeldt-Jakob disease (fCJD), which has
      imaging and clinical features that are similar to the sporadic form. The purpose
      of this study was to conduct a controlled and blinded evaluation of the
      sensitivity and specificity of MR imaging in this unique population. MATERIALS
      AND METHODS: We compared the MR imaging characteristics of 15 early stage
      familial CJD patients (age, 60 +/- 7 years) with a group of 22 healthy subjects
      from the same families (age, 61 +/- 8 years). MR imaging included diffusion
      weighted imaging (DWI), T2-weighted fast spin-echo imaging, and a fluid
      attenuated inversion recovery (FLAIR) sequence. The scans were rated for
      abnormalities by an experienced neuroradiologist blind to diagnosis, group
      assignment, age, and sex. RESULTS: Thirteen of 15 fCJD subjects had abnormal MR
      imaging. FLAIR signal intensity abnormality in the caudate or putamen nuclei
      demonstrated a sensitivity of 87% and specificity of 91%. DWI abnormality in the
      caudate nucleus showed a sensitivity of 73% and a specificity of 100%.
      Abnormalities in the thalamus (6 patients), cingulate gyrus (6 patients), frontal
      lobes (4 patients), and occipital lobes (3 patients) were best detected with DWI.
      No signal intensity abnormalities were demonstrated in the cerebellum. T2
      weighted and T1-weighted sequences were uninformative. CONCLUSIONS: FLAIR and DWI
      abnormalities in the caudate nucleus and putamen offer the best sensitivity and
      specificity for diagnosing fCJD. Our findings support recent recommendations that
      MR imaging should be added to the diagnostic evaluation of CJD.

PMID- 18635615
TI  - Persistence of gadolinium contrast enhancement in CSF: a possible harbinger of
      gadolinium neurotoxicity?

PMID- 18635616
TI  - Dynamic perfusion CT assessment of the blood-brain barrier permeability: first
      pass versus delayed acquisition.
AB  - BACKGROUND AND PURPOSE: The Patlak model has been applied to first-pass perfusion
      CT (PCT) data to extract information on blood-brain barrier permeability (BBBP)
      to predict hemorrhagic transformation in patients with acute stroke. However, the
      Patlak model was originally described for the delayed steady-state phase of
      contrast circulation. The goal of this study was to assess whether the first pass
      or the delayed phase of a contrast bolus injection better respects the
      assumptions of the Patlak model for the assessment of BBBP in patients with acute
      stroke by using PCT. MATERIALS AND METHODS: We retrospectively identified 125
      consecutive patients (29 with acute hemispheric stroke and 96 without) who
      underwent a PCT study by using a prolonged acquisition time up to 3 minutes. The
      Patlak model was applied to calculate BBBP in ischemic and nonischemic brain
      tissue. Linear regression of the Patlak plot was performed separately for the
      first pass and for the delayed phase of the contrast bolus injection. Patlak
      linear regression models for the first pass and the delayed phase were compared
      in terms of their respective square root mean squared errors (square root MSE)
      and correlation coefficients (R) by using generalized estimating equations with
      robust variance estimation. RESULTS: BBBP values calculated from the first pass
      were significantly higher than those from the delayed phase, both in nonischemic
      brain tissue (2.81 mL x 100 g(-1) x min(-1) for the first pass versus 1.05 mL x
      100 g(-1) x min(-1) for the delayed phase, P < .001) and in ischemic tissue (7.63
      mL x 100 g(-1) x min(-1) for the first pass versus 1.31 mL x 100 g(-1) x min(-1)
      for the delayed phase, P < .001). Compared with regression models from the first
      pass, Patlak regression models obtained from the delayed data were of better
      quality, showing significantly lower square root MSE and higher R. CONCLUSION:
      Only the delayed phase of PCT acquisition respects the assumptions of linearity
      of the Patlak model in patients with and without stroke.

PMID- 18635617
TI  - Comparison of multidetector CT angiography and MR imaging of cervical artery
      dissection.
AB  - BACKGROUND AND PURPOSE: Conventional angiography has been historically considered
      the gold standard for the diagnosis of cervical artery dissection, but MR
      imaging/MR angiography (MRA) and CT/CT angiography (CTA) are commonly used
      noninvasive alternatives. The goal of this study was to compare the ability of
      multidetector CT/CTA and MR imaging/MRA to detect common imaging findings of
      dissection. MATERIALS AND METHODS: Patients in the data base of our Stroke Center
      between 2003 and 2007 with dissections who had CT/CTA and MR imaging/MRA on
      initial work-up were reviewed retrospectively. Two neuroradiologists evaluated
      the images for associated findings of dissection, including acute ischemic
      stroke, luminal narrowing, vessel irregularity, wall thickening/hematoma,
      pseudoaneurysm, and intimal flap. The readers also subjectively rated each vessel
      on the basis of whether the imaging findings were more clearly displayed with
      CT/CTA or MR imaging/MRA or were equally apparent. RESULTS: Eighteen patients
      with 25 dissected vessels (15 internal carotid arteries [ICA] and 10 vertebral
      arteries [VA]) met the inclusion criteria. CT/CTA identified more intimal flaps,
      pseudoaneurysms, and high-grade stenoses than MR imaging/MRA. CT/CTA was
      preferred for diagnosis in 13 vessels (5 ICA, 8 VA), whereas MR imaging/MRA was
      preferred in 1 vessel (ICA). The 2 techniques were deemed equal in the remaining
      11 vessels (9 ICA, 2 VA). A significant preference for CT/CTA was noted for VA
      dissections (P < .05), but not for ICA dissections. CONCLUSION: Multidetector
      CT/CTA visualized more features of cervical artery dissection than MR
      imaging/MRA. CT/CTA was subjectively favored for vertebral dissection, whereas
      there was no technique preference for ICA dissection. In many cases, MR
      imaging/MRA provided complementary or confirmatory information, particularly
      given its better depiction of ischemic complications.

PMID- 18635618
TI  - MR imaging: influence of imaging technique and postprocessing on measurement of
      internal carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: MR angiography (MRA) is increasingly used as an
      alternative to digital subtraction angiography (DSA) to evaluate internal carotid
      artery (ICA) stenosis. Because MRA is not standardized in data acquisition and
      postprocessing, we sought to evaluate the effects of different acquisition
      techniques (time-of-flight MRA [TOF-MRA]) and contrast-enhanced MRA [CE-MRA]) and
      postprocessing methods (maximum intensity projection [MIP], multiplanar
      reformation [MPR], and volume-rendering on stenosis grading. MATERIALS AND
      METHODS: Fifty patients (33 men, 17 women) with symptomatic ICA stenosis were
      examined at 1.5T. Two imaging techniques and 3 postprocessing methods resulted in
      6 image datasets per patient. Two readers independently evaluated ICA stenosis
      according to the North American Symptomatic Carotid Endarterectomy Trial
      criteria. Interobserver variability was calculated with the Pearson correlation
      coefficient and simultaneous confidence intervals (CI). The relationship of the
      values of ICA stenosis between the techniques was assessed by means of
      simultaneous 95% Tukey CI. RESULTS: Interobserver agreement was high. Higher
      concordance was found for postprocessing techniques with TOF- than with CE-MRA;
      the mean difference between TOF-MPR and TOF-MIP was 0.4% (95% CI, -2.9%-3.8%).
      Stenosis values for CE-MPR differed significantly from those of CE volume
      rendering (7.2%; 95% CI, 3.9%-10.6%). CONCLUSION: Stenosis grading was found to
      be independent of the postprocessing technique except for comparison of CE-MPR
      with CE volume-rendering, with the volume-rendering technique resulting in higher
      stenosis values. MPR seems to be best-suited for measurement of ICA stenosis.
      Parameter setting is critical with volume-rendering, in which stenosis values
      were consistently higher compared with the other methods.

PMID- 18635619
TI  - 3T high-spatial-resolution contrast-enhanced MR angiography of the intracranial
      venous system with parallel imaging.
AB  - The diagnostic image quality of contrast-enhanced (CE) 3D MR venography (MRV) was
      prospectively compared with that of 2D time-of-flight (TOF) MRV and contrast
      enhanced 3D magnetization-prepared rapid acquisition of gradient echo (MPRAGE)
      sequences for the visualization of the intracranial venous system at 3T in 22
      patients. CE MRV provides high-quality images and was shown to be superior to TOF
      MRV and MPRAGE sequences in visualizing the normal intracranial venous system.

PMID- 18635620
TI  - Quality initiatives. Respiratory instructions for CT examinations of the lungs: a
      hands-on guide.
AB  - In computed tomographic (CT) examinations of the lung, accurate visualization of
      the natural contrast between the low attenuation of air and the relatively higher
      attenuation of vessels, airways, and interstitial structures requires cooperative
      and coordinated respiratory maneuvers by the patient. Inadequate respiratory
      maneuvers can influence differences in lung attenuation and lead to
      misinterpretation by (a) increasing attenuation to simulate disease in normal
      patients, (b) decreasing attenuation to simulate normal contrast in patients with
      disease, or (c) creating motion artifacts. For respiratory maneuvers to be
      effective, patients have to be instructed before the examination and coached
      during it. However, comprehensive descriptions of such instructions and coaching
      are lacking in the radiology literature. Therefore, respiratory instructions
      specifically for use in thoracic CT examinations have been devised. Along with
      patient coaching, use of these instructions can improve image quality. With this
      hands-on guide, both radiologists and technologists can optimize the respiratory
      instructions given to their patients and thereby improve the quality of thoracic
      CT examinations.

PMID- 18635621
TI  - Congratulations to the 2007 outstanding educator: Robert Novelline, MD.

PMID- 18635622
TI  - Informatics in radiology: IHE teaching file and clinical trial export integration
      profile: functional examples.
AB  - The digital revolution in radiology introduced the need for electronic export of
      medical images. However, the current export process is complicated and time
      consuming. In response to this continued difficulty, the Integrating the
      Healthcare Enterprise (IHE) initiative published the Teaching File and Clinical
      Trial Export (TCE) integration profile. The IHE TCE profile describes a method
      for using existing standards to simplify the export of key medical images for
      education, research, and publication. This article reviews the authors'
      experience in implementing the TCE profile in the following three processes: (a)
      the retrieval of images for a typical teaching file application within a TCE
      compliant picture archiving and communication system (PACS); (b) the export of
      images, independent of TCE compliance of the PACS, to a typical teaching file
      application; and (c) the TCE-compliant transfer of images for publication. These
      examples demonstrate methods with which the TCE profile can be implemented to
      ease the burden of collecting key medical images from the PACS.

PMID- 18635623
TI  - Role of static and dynamic MR imaging in surgical pelvic floor dysfunction.
AB  - Pelvic floor dysfunction (PFD) is a hidden women's health epidemic in the United
      States, with over 10% of women having a lifetime risk for undergoing a surgical
      repair for this problem. Given the paucity of understanding of PFD
      pathophysiology and the high rate of recurrence and repeat surgery, imaging plays
      a major role in its clinical management, especially for the preoperative
      assessment of patients with multicompartment defects and failed surgical repairs.
      The recent development of fast magnetic resonance (MR) imaging sequences allows
      noninvasive, radiation-free, rapid, high-resolution evaluation of the entire
      pelvis in one examination. The H line, M line, organ prolapse (HMO)
      classification system, which is applied to dynamic MR images, allows consistent
      standardization and grading of various forms of PFD. In addition, the HMO system
      clearly defines and differentiates between the two main components of PFD: pelvic
      floor relaxation and pelvic organ prolapse. In addition to serving as an
      objective diagnostic tool in patients with surgical PFD, MR imaging has
      tremendous potential to be used as a research tool in trying to understand the
      pathophysiology of these complex disorders.

PMID- 18635624
TI  - Imaging findings of complications and unusual manifestations of ovarian
      teratomas.
AB  - Ovarian teratomas can be associated with various complications and demonstrate a
      wide spectrum of clinical and imaging features. The complications include torsion
      (16% of ovarian teratomas), rupture (1%-4%), malignant transformation (1%-2%),
      infection (1%), and autoimmune hemolytic anemia (<1%). These complications
      require different therapeutic strategies; therefore, timely and accurate
      diagnosis of these complications is important for optimal patient treatment. In
      cases of complicated ovarian teratomas, the clinical manifestations provide only
      limited information and often overlap with those of other diseases. Furthermore,
      ovarian teratomas may have unusual clinical and imaging manifestations, thereby
      leading to misdiagnosis. These unusual manifestations include immature teratomas,
      monodermal teratomas (struma ovarii), combination tumors and collision tumors
      containing teratomas, and mature cystic teratomas without demonstrable fat or
      with pure fatty components. To provide adequate treatment and prevent
      misdiagnosis, it is necessary to be familiar with the imaging findings of both
      the complications and the unusual manifestations of ovarian teratomas.

PMID- 18635625
TI  - MR imaging of renal masses: correlation with findings at surgery and pathologic
      analysis.
AB  - Magnetic resonance (MR) imaging is useful in the characterization of renal
      masses. The MR imaging manifestations and pathologic diagnoses of 82 renal masses
      were reviewed and correlated. The MR imaging appearance of clear cell type renal
      cell carcinoma varies depending on the presence of cystic components, hemorrhage,
      and necrosis. Papillary renal cell carcinomas appear as well-encapsulated masses
      with homogeneous low signal intensity on T2-weighted images and homogeneous low
      level enhancement after the intravenous administration of contrast material, or
      as cystic hemorrhagic masses with peripheral enhancing papillary projections.
      Transitional cell carcinoma may be seen as an irregular, enhancing filling defect
      in the pelvicaliceal system or ureter. Lymphomatous masses are usually
      hypointense relative to the renal cortex on T2-weighted images and enhance
      minimally on delayed gadolinium-enhanced images. Bulk fat is a distinguishing
      feature of angiomyolipoma. Oncocytoma has a variable and nonspecific appearance
      at MR imaging. MR imaging findings may allow the characterization of various
      renal masses and can provide valuable information for their clinical management.

PMID- 18635626
TI  - Neoplastic and non-neoplastic proliferative disorders of the perirenal space:
      cross-sectional imaging findings.
AB  - The perirenal space, located between the anterior and the posterior renal
      fasciae, is shaped like an inverted cone with an apex that extends into the iliac
      fossa. Perirenal tumors and pseudotumors primarily originate either from the
      kidney or as part of a systemic disease process and have characteristic
      histopathologic features and biologic behavior. The lesions may be classified on
      the basis of their distribution and imaging features as solitary soft-tissue
      masses (renal cell carcinoma, lymphangioma, hemangioma, and leiomyoma), rindlike
      soft-tissue lesions (lymphoma, retroperitoneal fibrosis, and Erdheim-Chester
      disease), masses containing macroscopic fat (angiomyolipoma, liposarcoma,
      myelolipoma, and extramedullary hematopoiesis), and multifocal soft-tissue masses
      (metastases, plasma cell tumors). Because of overlap in imaging findings among
      these diverse perirenal lesions, a definitive diagnosis in most cases can be
      established only at histopathologic analysis. However, an imaging pattern-based
      approach may facilitate the diagnosis and optimal management of perirenal tumors
      and pseudotumors.

PMID- 18635627
TI  - Diagnostic imaging of solitary tumors of the spine: what to do and say.
AB  - Metastatic disease, myeloma, and lymphoma are the most common malignant spinal
      tumors. Hemangioma is the most common benign tumor of the spine. Other primary
      osseous lesions of the spine are more unusual but may exhibit characteristic
      imaging features that can help the radiologist develop a differential diagnosis.
      Radiologic evaluation of a patient who presents with osseous vertebral lesions
      often includes radiography, computed tomography (CT), and magnetic resonance (MR)
      imaging. Because of the complex anatomy of the vertebrae, CT is more useful than
      conventional radiography for evaluating lesion location and analyzing bone
      destruction and condensation. The diagnosis of spinal tumors is based on patient
      age, topographic features of the tumor, and lesion pattern as seen at CT and MR
      imaging. A systematic approach is useful for recognizing tumors of the spine with
      characteristic features such as bone island, osteoid osteoma, osteochondroma,
      chondrosarcoma, vertebral angioma, and aneurysmal bone cyst. In the remaining
      cases, the differential diagnosis may include other primary spinal tumors,
      vertebral metastases and major nontumoral lesions simulating a vertebral tumor,
      Paget disease, spondylitis, echinococcal infection, and aseptic osteitis. In many
      cases, vertebral biopsy is warranted to guide treatment.

PMID- 18635628
TI  - MR imaging of cartilage repair in the knee and ankle.
AB  - Because of the relative avascularity of articular cartilage, lesions that are
      caused by trauma or degeneration of the cartilage do not heal spontaneously and
      must be repaired surgically. The interventional procedures that have been
      developed for the repair of such lesions include abrasion, microfracture,
      autologous osteochondral transplantation, allograft transplantation, and
      autologous chondrocyte implantation. An accurate imaging assessment of the repair
      tissue is necessary in order to objectively evaluate the postoperative outcome.
      Magnetic resonance (MR) imaging and arthroscopy provide complementary information
      and are especially useful for follow-up evaluation of cartilage repair in the
      knee and ankle. Standard MR imaging techniques may be used postoperatively to
      evaluate the success of implantation and the state of cartilage healing. Newer
      matrix assessment techniques, which include delayed gadolinium-enhanced MR
      imaging and mapping of T1rho and T2 values, may provide useful supplemental
      information about the histologic and biochemical contents of reparative tissue.
      The normal postoperative appearance of the joints after cartilage repair varies
      according to the surgical technique used and the stage of healing. To identify
      potential complications, it is important to be familiar with the various repair
      procedures and the characteristic MR imaging features of the repair tissue at
      various postoperative intervals.

PMID- 18635629
TI  - Fetal skeletal dysplasia: an approach to diagnosis with illustrative cases.
AB  - Skeletal dysplasias are a heterogeneous group of conditions associated with
      various abnormalities of the skeleton. These conditions are caused by widespread
      disturbance of bone growth, beginning during the early stages of fetal
      development and evolving throughout life. Despite recent advances in imaging,
      fetal skeletal dysplasias are difficult to diagnose in utero due to a number of
      factors, including the large number of skeletal dysplasias and their phenotypic
      variability with overlapping features, lack of precise molecular diagnosis for
      many disorders, lack of a systematic approach, the inability of ultrasonography
      (US) to provide an integrated view, and variability in the time at which findings
      manifest in some skeletal dysplasias. US of suspected skeletal dysplasia involves
      systematic imaging of the long bones, thorax, hands and feet, skull, spine, and
      pelvis. Assessment of the fetus with three-dimensional US has been shown to
      improve diagnostic accuracy, since additional phenotypic features not detectable
      at two-dimensional US may be identified. The radiologist plays a major role in
      making an accurate diagnosis; however, representatives of other disciplines,
      including clinicians, molecular biologists, and pathologists, can also provide
      important diagnostic information.

PMID- 18635630
TI  - Neuroimaging in pediatric epilepsy: a multimodality approach.
AB  - Pediatric patients with intractable epilepsy represent a challenging clinical
      population. However, recent advances in neuroimaging with a multimodality imaging
      approach that combines fluorine 18 fluorodeoxyglucose positron emission
      tomography, magnetoencephalography, diffusion tensor imaging, and magnetic source
      imaging with conventional magnetic resonance imaging continue to improve
      diagnosis and treatment in affected patients. These advances are increasing the
      understanding of the underlying disease process and improving the ability to
      noninvasively detect epileptogenic foci that in the past went undetected and
      whose accurate localization is crucial for a good outcome following surgical
      resection.

PMID- 18635631
TI  - SPECT/CT imaging: clinical utility of an emerging technology.
AB  - Single-photon emission computed tomography (SPECT) has been a mainstay of nuclear
      medicine practice for several decades. More recently, combining the functional
      imaging available with SPECT and the anatomic imaging of computed tomography (CT)
      has gained more acceptance and proved useful in many clinical situations. Most
      vendors now offer integrated SPECT/CT systems that can perform both functions on
      one gantry and provide fused functional and anatomic data in a single imaging
      session. In addition to allowing anatomic localization of nuclear imaging
      findings, SPECT/CT also enables accurate and rapid attenuation correction of
      SPECT studies. These attributes have proved useful in many cardiac, general
      nuclear medicine, oncologic, and neurologic applications in which the SPECT
      results alone were inconclusive. Optimal clinical use of this rapidly emerging
      imaging modality requires an understanding of the fundamental principles of
      SPECT/CT, including quality control issues as well as potential pitfalls and
      limitations. The long-term clinical and economic effects of this technology have
      yet to be established.

PMID- 18635632
TI  - Mimics of cholangiocarcinoma: spectrum of disease.
AB  - Cholangiocarcinoma is the second most common primary malignant hepatobiliary
      neoplasm, accounting for approximately 15% of liver cancers. Diagnosis of
      cholangiocarcinoma is challenging and the prognosis is uniformly poor, with
      recurrence rates of 60%-90% after surgical resection. A wide spectrum of
      neoplastic and nonneoplastic conditions of the biliary tract may masquerade as
      cholangiocarcinoma, adding to the complexity of management in patients suspected
      to have cholangiocarcinoma. Mimics of cholangiocarcinoma constitute a
      heterogeneous group of entities that includes primary sclerosing cholangitis,
      recurrent pyogenic cholangitis, acquired immunodeficiency syndrome
      cholangiopathy, autoimmune pancreatitis, inflammatory pseudotumor, Mirizzi
      syndrome, xanthogranulomatous cholangitis, sarcoidosis, chemotherapy-induced
      sclerosis, hepatocellular carcinoma, metastases, melanoma, lymphoma, leukemia,
      and carcinoid tumors. These entities demonstrate characteristic histomorphology
      and variable clinicobiologic behaviors. The imaging findings of these disparate
      entities are protean and may be indistinguishable from those of
      cholangiocarcinoma. In most cases, a definitive diagnosis can be established only
      with histopathologic examination of a biopsy specimen.

PMID- 18635633
TI  - Neuroendocrine tumors: role of interventional radiology in therapy.
AB  - The management of neuroendocrine tumors (NETs) is complex. Although NETs can
      affect a variety of organ systems, hepatic metastatic disease in particular lends
      itself to a wide range of interventional treatment options. Prior detailed
      radiologic assessment and careful patient selection are required. Curative
      surgery should always be considered but is rarely possible. Embolization,
      radionuclide therapy, or ablative techniques may then be undertaken.
      Transcatheter arterial embolization (TAE) may be used alone or in combination
      with transcatheter arterial chemoembolization (TACE). NET type and extent of
      hepatic involvement are factors that can help predict the success of either TAE
      or TACE. Embolization techniques can also be useful in patients with nonhepatic
      NETs. Radionuclide therapy is emerging as a valuable adjunct and is dependent on
      positive somatostatin receptor status. Therapeutic radiopeptides may be delivered
      arterially. Ablative techniques have been shown to play a role in the palliation
      of symptoms and principally involve radiofrequency ablation. Hepatic cryotherapy
      and percutaneous ethanol injection have also been used. A multidisciplinary
      approach to treatment and follow-up is important. Imaging should involve dual
      phase multidetector computed tomography and contrast material-enhanced magnetic
      resonance imaging. The role of the interventional radiologist will continue to
      expand as imaging techniques become more refined.

PMID- 18635634
TI  - Steady-state MR imaging sequences: physics, classification, and clinical
      applications.
AB  - Steady-state sequences are a class of rapid magnetic resonance (MR) imaging
      techniques based on fast gradient-echo acquisitions in which both longitudinal
      magnetization (LM) and transverse magnetization (TM) are kept constant. Both LM
      and TM reach a nonzero steady state through the use of a repetition time that is
      shorter than the T2 relaxation time of tissue. When TM is maintained as multiple
      radiofrequency excitation pulses are applied, two types of signal are formed once
      steady state is reached: preexcitation signal (S-) from echo reformation; and
      postexcitation signal (S+), which consists of free induction decay. Depending on
      the signal sampled and used to form an image, steady-state sequences can be
      classified as (a) postexcitation refocused (only S+ is sampled), (b)
      preexcitation refocused (only S- is sampled), and (c) fully refocused (both S+
      and S- are sampled) sequences. All tissues with a reasonably long T2 relaxation
      time will show additional signals due to various refocused echo paths. Steady
      state sequences have revolutionized cardiac imaging and have become the standard
      for anatomic functional cardiac imaging and for the assessment of myocardial
      viability because of their good signal-to-noise ratio and contrast-to-noise ratio
      and increased speed of acquisition. They are also useful in abdominal and fetal
      imaging and hold promise for interventional MR imaging. Because steady-state
      sequences are now commonly used in MR imaging, radiologists will benefit from
      understanding the underlying physics, classification, and clinical applications
      of these sequences.

PMID- 18635635
TI  - Optimizing cardiac MR imaging: practical remedies for artifacts.
AB  - With ongoing technical advances in magnetic resonance (MR) imaging, the clinical
      demand for cardiac MR evaluations has been increasing. Cardiac MR imaging
      techniques have evolved from traditional spin-echo sequences to breath-hold
      spoiled gradient-echo and balanced steady-state free precession sequences. The
      most recently developed techniques allow evaluation of myocardial function,
      perfusion, and viability; coronary angiography; flow quantification; and standard
      morphologic assessments. However, even with the most sophisticated acquisition
      techniques, artifacts commonly occur at cardiac MR imaging. Knowledge of the
      origin, imaging appearance, and significance of these artifacts is essential to
      avoid misinterpreting them as true lesions. Some artifacts are caused by simple
      errors in positioning of the patient, coil, or electrocardiographic leads;
      radiofrequency interference from nearby electronic equipment; or metallic objects
      within the magnetic field. Others are directly related to a specific MR imaging
      sequence or technique. Accelerated imaging techniques such as parallel imaging,
      which are used to shorten acquisition and breath-hold times in cardiac
      evaluations, are particularly vulnerable to artifacts. If an artifact severely
      degrades image quality, the acquisition should be repeated with appropriate
      adjustments to decrease or eliminate the problem.

PMID- 18635636
TI  - Scenes from the past: Nikola Tesla and the discovery of X-rays.

PMID- 18635637
TI  - From the Archives of the AFIP. Pediatric orbit tumors and tumorlike lesions:
      osseous lesions of the orbit.
AB  - Many extraocular masses involving the pediatric orbit have an osseous origin. The
      most common is the dermoid inclusion cyst; these cystic lesions may contain lipid
      and are most often found near the zygomaticofrontal suture, adjacent to an
      indolent-appearing erosion of bone. Some primary bone lesions may involve the
      orbit, producing a lytic or dense lesion with enlargement of the bone; these
      lesions include fibrous dysplasia, juvenile ossifying fibroma, and osteosarcoma.
      Fibrous dysplasia tends to produce a mass of ground-glass appearance with
      longitudinal osseous expansion, whereas juvenile ossifying fibroma is likely to
      produce a mixed lytic and sclerotic lesion and focal osseous enlargement.
      Osteosarcoma causes marked bone destruction and variable osteoid production.
      Langerhans cell histiocytosis, an idiopathic reticuloendothelial proliferative
      disorder, tends to involve the bones of the skull, especially the lateral orbital
      roof; it produces lytic destruction of bone with a sclerotic rim and a large
      intraorbital soft-tissue mass. Granulocytic sarcoma is a solid tumor that may
      occur in children with myelogenous leukemia. These tumors tend to arise in the
      subperiosteum of the lateral orbital wall, although they usually do not disrupt
      the bone. Finally, the orbit is a common site for bone metastases from
      neuroblastoma, which cause aggressive periosteal reaction in the orbital roof or
      lateral wall. The last three conditions are often bilateral. At imaging
      evaluation, osseous lesions may appear similar to each other and to nonosseous
      masses of the orbit. Knowledge of the pathologic features of these tumors and how
      these features are reflected in their imaging appearances may help radiologists
      differentiate them.

PMID- 18635638
TI  - Best cases from the AFIP: Adamantinoma of the tibia and fibula with cytogenetic
      analysis.

PMID- 18635639
TI  - Best cases from the AFIP: Multilocular cystic renal tumor: cystic nephroma.

PMID- 18635640
TI  - A novel mechanism linking corticotrophin-releasing factor to ventral tegmental
      area dopamine neuron firing.

PMID- 18635641
TI  - Activation of recombinant NR1/NR2C NMDA receptors.
AB  - The N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate receptors
      comprises both NR1 and NR2 subunits, and plays numerous roles in both
      physiological and pathophysiological processes in the central nervous system
      (CNS). NR2C-containing NMDA receptors are most abundant in cerebellum, thalamus
      and olfactory bulb, and are also expressed in oligodendrocytes and hippocampal
      interneurons. We have used patch clamp recording to explore the activation
      properties of recombinant NR1/NR2C receptors expressed in HEK293 cells. NR1/NR2C
      receptors activated by a maximally effective concentration of glutamate and
      glycine had two main conductance levels of 45 pS and 28 pS when the extracellular
      Ca(2+) concentration was 0.5 mm and the holding potential was -80 mV. The
      occurrence of the lower subconductance state was reduced in the absence of
      extracellular Ca(2+). The distribution of closed durations recorded from patches
      with a high probability of containing only one active channel were best fitted by
      five exponential functions; the apparent open duration histogram could be fitted
      by two exponential functions (n = 10 patches). The apparent mean open time of
      NR1/NR2C receptors was brief (0.52 +/- 0.04 ms), suggesting that the stability of
      the open state of the NR1/NR2C receptors is lower than other NR2-containing
      receptors. NR1/NR2C open probability was exceptionally low, being 0.011 +/- 0.002
      in patches containing a single active receptor (n = 8). Fast agonist
      concentration jumps were performed on outside out patches with multiple NR1/NR2C
      channels, which activated with a 10-90% rise time of 3.9 +/- 0.4 ms, faster than
      other NR2-containing receptors. The deactivation time constant after a brief (5-8
      ms) application of a maximally effective concentration of agonists was 319 +/- 34
      ms. The majority of the patches also showed a modest level of desensitization
      that could be described by either a single or a double exponential time course
      with the fastest time constant between 15 and 47 ms. Conceptual models of
      activation were fitted using the maximum interval likelihood (MIL) method to the
      sequence of open and closed durations recorded from outside-out patches that
      contained one active NR1/NR2C channel. NR1/NR2C receptor properties including
      modest desensitization and low open probability could be described by gating
      schemes similar to those previously proposed for other NMDA receptor subunit
      combinations.

PMID- 18635642
TI  - Synapses on NG2-expressing progenitors in the brain: multiple functions?
AB  - Progenitor cells expressing the proteoglycan NG2 represent approximately 5% of
      the total cells in the adult brain, and are found both in grey and white matter
      regions where they give rise to oligodendrocytes. The finding that these cells
      receive synaptic contacts from excitatory and inhibitory neurons has not only
      raised major interest in the possible roles of these synapses, but also
      stimulated further research on the developmental and cellular functions of NG2
      expressing (NG2(+)) progenitors themselves in the context of neural circuit
      physiology. Here we review recent findings on the functional properties of the
      synapses on NG2(+) cells in grey and white matter regions of the brain. In this
      review article we make an attempt to integrate current knowledge on the cellular
      and developmental properties of NG2(+) progenitors with the functional attributes
      of their synapses, in order to understand the physiological relevance of neuron
      NG2(+) progenitor signal transmission. We propose that, although NG2(+)
      progenitors receive synaptic contact in all brain regions where they are found,
      their synapses might have different developmental and functional roles, probably
      reflecting the distinct functions of NG2(+) progenitors in the brain.

PMID- 18635643
TI  - Elevation in cerebral blood flow velocity with aerobic fitness throughout healthy
      human ageing.
AB  - It is known that cerebral blood flow declines with age in sedentary adults,
      although previous studies have involved small sample sizes, making the exact
      estimate of decline imprecise and the effects of possible moderator variables
      unknown. Animal studies indicate that aerobic exercise can elevate cerebral blood
      flow; however, this possibility has not been examined in humans. We examined how
      regular aerobic exercise affects the age-related decline in blood flow velocity
      in the middle cerebral artery (MCAv) in healthy humans. Maximal oxygen
      consumption, body mass index (BMI), blood pressure and MCAv were measured in
      healthy sedentary (n = 153) and endurance-trained (n = 154) men aged between 18
      and 79 years. The relationships between age, training status, BMI and MCAv were
      examined using analysis of covariance methods. Mean +/- s.e.m. estimates of
      regression coefficients and 95% confidence intervals (95% CI) were calculated.
      The age-related decline in MCAv was -0.76 +/- 0.04 cm s(-1) year(-1) (95% CI = 
      0.69 to -0.83, r(2) = 0.66, P < 0.0005) and was independent of training status (P
      = 0.65). Nevertheless, MCAv was consistently elevated by 9.1 +/- 3.3 cm s(-1) (CI
      = 2.7-15.6, P = 0.006) in endurance-trained men throughout the age range. This
      approximately 17% difference between trained and sedentary men amounted to an
      approximate 10 year reduction in MCAv 'age' and was robust to between-group
      differences in BMI and blood pressure. Regular aerobic-endurance exercise is
      associated with higher MCAv in men aged 18-79 years. The persistence of this
      finding in older endurance-trained men may therefore help explain why there is a
      lower risk of cerebrovascular disease in this population.

PMID- 18635644
TI  - Interaction between the ventilatory and cerebrovascular responses to hypo- and
      hypercapnia at rest and during exercise.
AB  - Cerebrovascular reactivity to changes in the partial pressure of arterial carbon
      dioxide (P(a,CO(2))) via limiting changes in brain [H(+)] modulates ventilatory
      control. It remains unclear, however, how exercise-induced alterations in
      respiratory chemoreflex might influence cerebral blood flow (CBF), in particular
      the cerebrovascular reactivity to CO(2). The respiratory chemoreflex system
      controlling ventilation consists of two subsystems: the central controller
      (controlling element), and peripheral plant (controlled element). In order to
      examine the effect of exercise-induced alterations in ventilatory chemoreflex on
      cerebrovascular CO(2) reactivity, these two subsystems of the respiratory
      chemoreflex system and cerebral CO(2) reactivity were evaluated (n = 7) by the
      administration of CO(2) as well as by voluntary hypo- and hyperventilation at
      rest and during steady-state exercise. During exercise, in the central
      controller, the regression line for the P(a,CO(2))-minute ventilation (VE)
      relation shifted to higher VE and P(a,CO(2)) with no change in gain (P = 0.84).
      The functional curve of the peripheral plant also reset rightward and upward
      during exercise. However, from rest to exercise, gain of the peripheral plant
      decreased, especially during the hypercapnic condition (-4.1 +/- 0.8 to -2.0 +/-
      0.2 mmHg l(-1) min(-1), P = 0.01). Therefore, under hypercapnia, total
      respiratory loop gain was markedly reduced during exercise (-8.0 +/- 2.3 to -3.5
      +/- 1.0 U, P = 0.02). In contrast, cerebrovascular CO(2) reactivity at each
      condition, especially to hypercapnia, was increased during exercise (2.4 +/- 0.2
      to 2.8 +/- 0.2% mmHg(-1), P = 0.03). These findings indicate that, despite an
      attenuated chemoreflex system controlling ventilation, elevations in
      cerebrovascular reactivity might help maintain CO(2) homeostasis in the brain
      during exercise.

PMID- 18635645
TI  - Movement of the tongue during normal breathing in awake healthy humans.
AB  - Electromyographic (EMG) activity of the airway muscles suggest that genioglossus
      is the primary upper airway dilator muscle. However, EMG data do not necessarily
      translate into tissue motion and most imaging modalities are limited to
      assessment of the surfaces of the upper airway. In this study, we hypothesized
      that genioglossus moves rhythmically during the respiratory cycle and that the
      motion within is inhomogeneous. A 'tagged' magnetic resonance imaging technique
      was used to characterize respiratory-related tissue motions around the human
      upper airway in quiet breathing. Motion of airway tissues at different segments
      of the eupnoeic respiratory cycle was imaged in six adult subjects by triggering
      the scanner at the end of inspiration. Displacements of the 'tags' were analysed
      using the harmonic phase method (HARP). Respiratory timing was monitored by a
      band around the upper abdomen. The genioglossus moved during the respiratory
      cycle. During expiration, the genioglossus moved posteriorly and during
      inspiration, it moved anteriorly. The degree of motion varied between subjects.
      The maximal anteroposterior movement of a point tracked on the genioglossus was
      1.02 +/- 0.54 mm (mean +/- s.d.). The genioglossus moved over the geniohyoid
      muscle, with minimal movement in other muscles surrounding the airway at the
      level of the soft palate. Local deformation of the tongue was analysed using two
      dimensional strain maps. Across the respiratory cycle, positive strains within
      genioglossus reached peaks of 17.5 +/- 9.3% and negative strains reached peaks of
      -16.3 +/- 9.3% relative to end inspiration. The patterns of strains were
      consistent with elongation and compression within a constant volume structure.
      Hence, these data suggest that even during respiration, the tongue behaves as a
      muscular hydrostat.

PMID- 18635646
TI  - Polarized intrinsic neural reflexes in response to colonic elongation.
AB  - Propulsion in both small and large intestine is largely mediated by the
      peristaltic reflex; despite this, transit through the shorter colon is at least
      10 times slower. Recently we demonstrated that elongating a segment of colon
      releases nitric oxide (NO) to inhibit peristalsis. The aims of this study were to
      determine if colonic elongation was physiologically significant, and whether
      elongation activated polarized intrinsic neural reflexes. Video imaging monitored
      fecal pellet evacuation from isolated guinea-pig colons full of pellets.
      Recordings were made from the circular muscle (CM) and longitudinal muscle (LM)
      in flat sheet preparations using either intracellular microelectrode or Ca(2+)
      imaging techniques. Full colons were 158.1 +/- 6.1% longer than empty colons. As
      each pellet was expelled, the colon shortened and pellet velocity increased
      exponentially (full 0.34, empty 1.01 mm s(-1)). In flat sheet preparations,
      maintained circumferential stretch generated ongoing peristaltic activity (oral
      excitatory and anal inhibitory junction potentials) and Ca(2+) waves in LM and
      CM. Colonic elongation (140% of its empty slack length) applied oral to the
      recording site abolished these activities, whereas anal elongation significantly
      increased the frequency and amplitude of ongoing peristaltic activity. Oral
      elongation inhibited the excitation produced by anal elongation; this inhibitory
      effect was reversed by blocking NO synthesis. Pelvic nerve stimulation elicited
      polarized responses that were also suppressed by NO released during colonic
      elongation. In conclusion, longitudinal stretch excites specific mechanosensitive
      ascending and descending interneurons, leading to activation of polarized
      reflexes. The dominance of the descending inhibitory reflex leads to slowed
      emptying of pellets in a naturally elongated colon.

PMID- 18635647
TI  - Role of the commissural inhibitory system in vestibular compensation in the rat.
AB  - We investigated the role of the vestibular commissural inhibitory system in
      vestibular compensation (VC, the behavioural recovery that follows unilateral
      vestibular loss), using in vivo microdialysis to measure GABA levels in the
      bilateral medial vestibular nucleus (MVN) at various times after unilateral
      labyrinthectomy (UL). Immediately after UL, in close correlation with the
      appearance of the characteristic oculomotor and postural symptoms, there is a
      marked increase in GABA release in the ipsi-lesional MVN. This is not prevented
      by bilateral flocculectomy, indicating that it is due to hyperactivity of
      vestibular commissural inhibitory neurones. Over the following 96 h, as VC occurs
      and the behavioural symptoms ameliorate, the ipsi-lesional GABA levels return to
      near-normal. Contra-lesional GABA levels do not change significantly in the
      initial stages of VC, but decrease at late stages so that when static symptoms
      have abated there remains a significant difference between the MVNs of the two
      sides. We also investigated the role of the commissural inhibition in Bechterew's
      phenomenon, by reversibly inactivating the intact contra-lesional labyrinth in
      compensating animals through superfusion of local anaesthetic on the round
      window. Transient inactivation of the intact labyrinth elicited the lateralized
      behaviour described by Bechterew, but did not alter the GABA levels in either
      MVN, suggesting the involvement of distinct cellular mechanisms. These findings
      indicate that an imbalanced commissural inhibitory system is a root cause of the
      severe oculomotor and postural symptoms of unilateral vestibular loss, and that
      re-balancing of commissural inhibition occurs in parallel with the subsequent
      behavioural recovery during VC.

PMID- 18635648
TI  - Monosynaptic convergence of C- and Adelta-afferent fibres from different
      segmental dorsal roots on to single substantia gelatinosa neurones in the rat
      spinal cord.
AB  - Although it is known that each spinal cord segment receives thin-fibre inputs
      from several segmental dorsal roots, it remains unclear how these inputs converge
      at the cellular level. To study whether C- and Adelta-afferents from different
      roots can converge monosynaptically on to a single substantia gelatinosa (SG)
      neurone, we performed tight-seal recordings from SG neurones in the entire lumbar
      enlargement of the rat spinal cord with all six segmental (L1-L6) dorsal roots
      attached. The neurones in the spinal cord were visualized using our recently
      developed oblique LED illumination technique. Individual SG neurones from the
      spinal segment L4 or L3 were voltage clamped to record the monosynaptic EPSCs
      evoked by stimulating ipsilateral L1-L6 dorsal roots. We found that one-third of
      the SG neurones receive simultaneous monosynaptic inputs from two to four
      different segmental dorsal roots. For the SG neurones from segment L4, the major
      monosynaptic input was from the L4-L6 roots, whereas for those located in segment
      L3 the input pattern was shifted to the L2-L5 roots. Based on these data, we
      propose a new model of primary afferent organization where several C- or Adelta
      fibres innervating one cutaneous region (peripheral convergence) and ascending
      together in a common peripheral nerve may first diverge at the level of spinal
      nerves and enter the spinal cord through different segmental dorsal roots, but
      finally re-converge monosynaptically on to a single SG neurone. This organization
      would allow formation of precise and robust neural maps of the body surface at
      the spinal cord level.

PMID- 18635649
TI  - Somatic Ca2+ transients do not contribute to inspiratory drive in preBotzinger
      Complex neurons.
AB  - PreBotzinger Complex (preBotC) neurons are postulated to underlie respiratory
      rhythm generation. The inspiratory phase of the respiratory cycle in vitro
      results from preBotC neurons firing synchronous bursts of action potentials (APs)
      on top of 10-20 mV, 0.3-0.8 s inspiratory drive potentials. Is the inspiratory
      drive in individual neurons simply the result of the passive integration of
      inspiratory-modulated synaptic currents or do active processes modulate these
      currents? As somatic Ca(2+) is known to increase during inspiration, we
      hypothesized that it affects inspiratory drive. We combined whole cell recording
      in an in vitro slice preparation with Ca(2+) microfluorometry to detect single
      inspiratory neuron somatic Ca(2+) transients with high temporal resolution (
      approximately mus). In neurons loaded with either Fluo-4 or Oregon Green BAPTA 5
      N, we observed Ca(2+) transients associated with each AP. During inspiration,
      significant somatic Ca(2+) influx was a direct consequence of activation of
      voltage-gated Ca(2+) channels by APs. However, when we isolated the inspiratory
      drive potential in active preBotC neurons (by blocking APs with intracellular QX
      314 or by hyperpolarization), we did not detect somatic Ca(2+) transients; yet,
      the parameters of inspiratory drive were the same with or without APs. We
      conclude that, in the absence of APs, somatic Ca(2+) transients do not shape the
      somatic inspiratory drive potential. This suggests that in preBotC neurons,
      substantial and widespread somatic Ca(2+) influx is a consequence of APs during
      the inspiratory phase and does not contribute substantively to the inspiratory
      drive potential. Given evidence that the Ca(2+) buffer BAPTA can significantly
      reduce inspiratory drive, we hypothesize that dendritic Ca(2+) transients amplify
      inspiratory-modulated synaptic currents.

PMID- 18635650
TI  - Molecular regulation of the hypothalamic-pituitary-adrenal axis in adult male
      guinea pigs after prenatal stress at different stages of gestation.
AB  - Studies in humans and animals have demonstrated that maternal stress during fetal
      development can lead to altered hypothalamic-pituitary-adrenal (HPA) axis
      function and behaviour postnatally. We have previously shown adult male guinea
      pigs that were born to mothers exposed to a stressor during the phase of rapid
      fetal brain growth (gestational days (GD) 50, 51 and 52; prenatal stress (PS)50)
      exhibit significantly increased basal plasma cortisol levels. In contrast, male
      guinea pig offspring whose mothers were exposed to stress later in gestation
      (GD60, 61 and 62; PS60) exhibited a significantly higher plasma cortisol response
      to activation of the HPA axis. In the present study, we hypothesized that the
      endocrine changes in HPA axis function observed in male guinea pig offspring
      would be reflected by altered molecular regulation of the HPA axis.
      Corticosteroid receptors in the hippocampus, hypothalamus and pituitary were
      measured, as well as corticotropin-releasing hormone (CRH), pro-opiomelanocortin
      (POMC) and adrenal enzymes in the paraventricular nucleus, pituitary and adrenal
      cortex, respectively, by in situ hybridization and Western blot. PS50 male
      offspring exhibited a significant reduction in glucocorticoid receptor (GR) mRNA
      (P <0.01) in the CA3 region of the hippocampus and significantly increased POMC
      mRNA (P <0.05) in the pituitary, consistent with the increase in basal HPA axis
      activity observed. In line with elevated activity of the HPA axis, both PS50 and
      PS60 male offspring exhibited significantly higher steroidogenic factor (SF)-1 (P
      <0.001) and melanocortin 2 receptor (MC2-R) mRNA (P <0.001) in the adrenal
      cortex. This study demonstrates that short periods of prenatal stress during
      critical windows of neuroendocrine development affect the expression of key
      regulators of HPA axis activity leading to the changes in endocrine function
      observed in prenatally stressed male offspring. Further, these changes are
      dependent on the timing of the maternal stressor, a pattern that is emerging in
      human studies.

PMID- 18635651
TI  - In vivo profiling of estrogen receptor/specificity protein-dependent
      transactivation.
AB  - 17beta-Estradiol (E2) activates the estrogen receptor (ER) through multiple
      genomic and nongenomic pathways in various tissues/organs. ERalpha/specificity
      protein-dependent activation of E2-responsive genes containing GC-rich promoters
      has been identified in breast and other cancer cell lines, and in this study, we
      describe transgenic animals overexpressing a transgene containing three tandem GC
      rich sites linked to a minimal TATA or thymidine kinase promoter and a luciferase
      gene. Several mouse lines expressing the transgenes were characterized and, in
      line 15, E2 induced a 9-fold increase in luciferase activity in the female mouse
      uterus, and the synthetic estrogens bisphenol A and nonylphenol also induced
      uterine luciferase activity. The pure antiestrogen ICI 182,780 induced luciferase
      activity in the mouse uterus, and similar results were observed for ICI 182,780
      in breast cancer cells transfected with this construct. Differences in the ER
      agonist and antagonist activities of E2, nonylphenol, bisphenol A, and ICI
      182,780 were investigated in the male testis and penis and the male and female
      stomach in line 15 transgenic mice. All of these tissues were hormone responsive;
      however, the patterns of induced or repressed luciferase activity were ligand
      structure, tissue, and sex dependent. These results demonstrate for the first
      time hormonal activation or repression of a GC-rich promoter in vivo, and the
      results suggest that the ERalpha/specificity protein pathway may contribute to E2
      dependent induction and repression of genes.

PMID- 18635652
TI  - Regulator of G protein signaling-4 controls fatty acid and glucose homeostasis.
AB  - Circulating free fatty acids are a reflection of the balance between lipogenesis
      and lipolysis that takes place mainly in adipose tissue. We found that mice
      deficient for regulator of G protein signaling (RGS)-4 have increased circulating
      catecholamines, and increased free fatty acids. Consequently, RGS4-/- mice have
      increased concentration of circulating free fatty acids; abnormally accumulate
      fatty acids in liver, resulting in liver steatosis; and show a higher degree of
      glucose intolerance and decreased insulin secretion in pancreas. We show in this
      study that RGS4 controls adipose tissue lipolysis through regulation of the
      secretion of catecholamines by adrenal glands. RGS4 controls the balance between
      adipose tissue lipolysis and lipogenesis, secondary to its role in the regulation
      of catecholamine secretion by adrenal glands. RGS4 therefore could be a good
      target for the treatment of metabolic diseases.

PMID- 18635653
TI  - Molecular cloning, characterization, and evolutionary analysis of estrogen
      receptors from phylogenetically ancient fish.
AB  - Estrogens are necessary for ovarian differentiation during a critical
      developmental stage in many vertebrates, and they promote the growth and
      differentiation of the adult female reproductive system. To understand the
      evolution of vertebrate estrogen receptors (ESRs) and to evaluate estrogen
      receptor-ligand interactions in phylogenetically ancient fish, we used PCR
      techniques to isolate the cDNA encoding ESRs from lungfish, sturgeon, and gar.
      Sequence analyses indicate that these fishes have two ESRs, ESR1 (ERalpha) and
      ESR2 (ERbeta), as previously reported for other vertebrate species, but a second
      type of ESR2 (ERbeta2) was not found as has been reported in a number of teleost
      fishes. Phylogenetic analysis of the ESR sequences indicated that the lungfish
      ESRs are classified to the tetrapod ESR group, not with the teleost fish ESRs as
      are the ESRs from gar and sturgeon. Using transient transfection assays of
      mammalian cells, ESR proteins from these three ancient fishes displayed estrogen
      dependent activation of transcription from an estrogen-responsive-element
      containing promoter. We also examined the estrogenic potential of o,p'-dichloro
      diphenyl-trichloroethane (o,p'-DDT) and p,p'-DDT as well as one of its common
      metabolites, p,p'-dichloro-diphenyl-ethylene (p,p'-DDE) on the ESRs from these
      fishes. Lungfish ESR1 was less sensitive to DDT/DDE than the ESR1 from the other
      two fishes. The response of lungfish ESR1 to these pesticides is similar to the
      pattern obtained from salamander ESR1. These data provide a basic tool allowing
      future studies examining the receptor-ligand interactions and endocrine
      disrupting mechanisms in three species of phylogenetically ancient fish and also
      expands our knowledge of ESR evolution.

PMID- 18635654
TI  - Follicle-stimulating hormone responses to kisspeptin in the female rat at the
      preovulatory period: modulation by estrogen and progesterone receptors.
AB  - Ovulation is triggered by the preovulatory surge of gonadotropins that, in
      rodents, is defined by the concomitant rise in circulating LH and FSH at the
      afternoon of proestrus (primary surge), followed by persistently elevated FSH
      levels at early estrus (secondary surge). In recent years, kisspeptins, products
      of the KiSS-1 gene that act via G protein-coupled receptor 54, have emerged as an
      essential hypothalamic conduit for the generation of the preovulatory LH surge by
      conveying positive feedback effects of estradiol onto GnRH neurons, an event that
      involves not only estradiol-induced transcription of the KiSS-1 gene at the
      anteroventral periventricular nucleus but also its ability to modulate GnRH/LH
      responses to kisspeptin. However, little is known about the potential modulation
      of FSH responsiveness to kisspeptin by sex steroids in the cyclic female. We
      report herein analyses on the consequences of selective blockade of estrogen
      receptors (ER)-alpha and -beta, as well as progesterone receptor (PR), on the
      ovulatory surges of FSH and their modulation by kisspeptin. Antagonism of ERalpha
      or PR equally blunted the primary and secondary surges of FSH and nullified FSH
      responses to kisspeptin at the preovulatory period. Conversely, selective
      blockade of ERbeta failed to induce major changes in terms of endogenous FSH
      surges, yet it decreased FSH responses to exogenous kisspeptin. In contrast, FSH
      responses to GnRH were fully conserved after ERbeta blockade and partially
      preserved after inhibition of ERalpha and PR signaling. Finally, secondary FSH
      secretion was rescued by kisspeptin in females with selective blockade of ERalpha
      but not PR. In sum, our results substantiate a concurrent, indispensable role of
      ERalpha and PR in the generation of FSH surges and the stimulation of FSH
      responses to kisspeptin at the ovulatory period. In addition, our data suggest
      that ERbeta might operate as a subtle, positive modulator of the preovulatory FSH
      responses to kisspeptin, a role that is opposite to its putative inhibitory
      action on kisspeptin-induced LH secretion and might contribute to the
      dissociation of gonadotropin secretion at the ovulatory phase in the cyclic
      female rat.

PMID- 18635655
TI  - Maternal and postnatal overnutrition differentially impact appetite regulators
      and fuel metabolism.
AB  - Maternal obesity is increasing, and it is known that the intrauterine experience
      programs fetal and newborn metabolism. However, the relative contributions of pre
      or postnatal factors are unknown. We hypothesized that maternal overnutrition
      caused by long-term maternal obesity would exert a stronger detrimental impact
      than postnatal overnutrition on offspring metabolic homeostasis, with additional
      postnatal overnutrition exaggerating these alterations. Female Sprague Dawley
      rats were exposed to chow or high-fat cafeteria diet for 5 wk before mating and
      throughout gestation and lactation. On postnatal d 1, litters were adjusted to
      three per litter to induce postnatal overnutrition (vs. 12 in control).
      Hypothalamic appetite regulators neuropeptide Y and proopiomelanocortin, glucose
      transporter 4, and lipid metabolic markers were measured. At postnatal d 20, male
      pups born of obese dams, or those overnourished postnatally, were 42% heavier
      than controls; combining both interventions led to 80% greater body weight.
      Maternal obesity increased pup adiposity and led to glucose intolerance in
      offspring; these were exaggerated by additional postnatal overnutrition during
      lactation. Maternal obesity was also linked to hyperlipidemia in offspring and
      reduced hypothalamic neuropeptide Y and increased proopiomelanocortin mRNA
      expression. Postnatal overnutrition of offspring from obese dams amplified these
      hypothalamic changes. Both maternal and postnatal overnutrition reduced muscle
      glucose transporter 4. Adipose carnitine palmitoyl-transferase-1 and adipose
      triglyceride lipase mRNA was up-regulated only by postnatal overnutrition.
      Maternal overnutrition appears to alter central appetite circuits and promotes
      early-onset obesity; postnatal overnutrition interacted to cause peripheral lipid
      and glucose metabolic disorders, supporting the critical message to reduce early
      life adverse nutritional impact.

PMID- 18635656
TI  - Classical estrogen receptor alpha signaling mediates negative and positive
      feedback on gonadotropin-releasing hormone neuron firing.
AB  - During the female reproductive cycle, the neuroendocrine action of estradiol
      switches from negative feedback to positive feedback to initiate the preovulatory
      GnRH and subsequent LH surges. Estrogen receptor-alpha (ERalpha) is required for
      both estradiol negative and positive feedback regulation of LH. ERalpha may
      signal through estrogen response elements (EREs) in DNA and/or via ERE
      independent pathways. Previously, a knock-in mutant allele (ERalpha-/AA) that
      selectively restores ERE-independent signaling onto the ERalpha-/- background was
      shown to confer partial negative but not positive estradiol feedback on serum LH.
      The current study investigated the roles of the ERE-dependent and ERE-independent
      ERalpha pathways for estradiol feedback at the level of GnRH neuron firing
      activity. The above ERalpha genetic models were crossed with GnRH-green
      fluorescent protein mice to enable identification of GnRH neurons in brain
      slices. Targeted extracellular recordings were used to monitor GnRH neuron firing
      activity using an ovariectomized, estradiol-treated mouse model that exhibits
      diurnal switches between negative and positive feedback. In wild-type mice, GnRH
      neuron firing decreased in response to estradiol during negative feedback and
      increased during positive feedback. In contrast, both positive and negative
      responses to estradiol were absent in GnRH neurons from ERalpha-/- and ERalpha
      /AA mice. ERE-dependent signaling is thus required to increase GnRH neuron firing
      to generate a GnRH/LH surge. Furthermore, ERE-dependent and -independent ERalpha
      signaling pathways both appear necessary to mediate estradiol negative feedback
      on serum LH levels, suggesting central and pituitary estradiol feedback may use
      different combinations of ERalpha signaling pathways.

PMID- 18635657
TI  - Prostaglandin synthesis, metabolism, and signaling potential in the rhesus
      macaque corpus luteum throughout the luteal phase of the menstrual cycle.
AB  - Prostaglandins in the corpus luteum (CL) reportedly serve as luteotropic and
      luteolytic agents. Based mainly on studies conducted in domesticated animals and
      rodents, prostaglandin E2 (PGE2) is generally considered a luteotropic factor,
      whereas uterine-derived prostaglandin F2alpha (PGF2alpha) initiates luteolysis.
      However, the role of prostaglandins in regulating primate luteal structure
      function is poorly understood. Therefore, a comprehensive analysis of individual
      mRNA or proteins that are involved in PGE2 and PGF2alpha biosynthesis,
      metabolism, and signaling was performed using CL obtained at distinct stages of
      the luteal life span during the menstrual cycle in rhesus monkeys. Peak levels of
      proteins involved in PGE2 synthesis (prostaglandin-endoperoxide synthase 2,
      microsomal PGE2 synthase-1) and signaling (PGE2 receptor 3) occurred during
      periods corresponding to development and maintenance of the primate CL.
      Immunohistochemistry studies indicated that large luteal cells express PGE2
      synthesizing and signaling proteins. Expression of PGE2 synthesizing and
      signaling proteins significantly decreased preceding the period of functional
      regression of the CL, which also coincided with increasing levels of PGF2alpha
      receptor protein expression within the large luteal cells. Moreover, significant
      levels of mRNA expression for several aldoketo reductase family members that
      synthesize PGF2alpha from other prostaglandins were observed throughout the
      rhesus macaque luteal phase, thus supporting the possibility of intraluteal
      PGF2alpha production. Collectively, our results indicate that there may be
      intraluteal synthesis and signaling of PGE2 during development and maintenance of
      the primate CL, followed by a shift to intraluteal PGF2alpha synthesis and
      signaling as the CL nears the time of luteolysis.

PMID- 18635659
TI  - Hypothalamic-pituitary-adrenal axis activity of newborn mice rapidly desensitizes
      to repeated maternal absence but becomes highly responsive to novelty.
AB  - In CD1 mice we investigated the hypothalamic-pituitary-adrenal (HPA) axis
      response to maternal separation for 8 h daily from postnatal d 3 to 5. At d 3 a
      slow separation-induced corticosterone response developed that peaked after 8 h,
      and the pups became responsive to stressors. On the second and third day, the
      response to 8 h separation rapidly attenuated, whereas the response to novelty
      did not, a pattern reflected by the hypothalamic c-fos mRNA response. If maternal
      separation and exposure to novelty were combined, then after the third such daily
      exposure, the sensitivity to the stressor was further enhanced. Meanwhile, basal
      corticosterone and ACTH levels were persistently suppressed 16 h after pups were
      reunited with their mothers. To explain the HPA axis desensitization after
      repeated separation, we found that circulating ghrelin levels increased and
      glucose levels decreased after all periods of maternal separation, ruling out a
      role of altered metabolism. Glucocorticoid feedback was not involved either
      because a glucocorticoid receptor antagonist amplified the corticosterone
      response after the first but became ineffective after the third separation. In
      contrast, a mineralocorticoid receptor antagonist decreased and increased
      corticosterone levels after the first and third period of separation,
      respectively. In conclusion, the newborn's HPA axis readily desensitizes to
      repeated daily maternal separation, but continues to respond to novelty in a
      manner influenced by a central mineralocorticoid receptor- rather than
      glucocorticoid receptor-mediated mechanism.

PMID- 18635658
TI  - Leptin regulates peripheral lipid metabolism primarily through central effects on
      food intake.
AB  - The metabolic effects of leptin may involve both centrally and peripherally
      mediated actions with a component of the central actions potentially independent
      of alterations in food intake. Ob/ob mice have significant abnormalities in lipid
      metabolism, correctable by leptin administration. We used ob/ob mice to study the
      relative importance of the subtypes of actions of leptin (central vs. peripheral;
      food intake dependent vs. independent) on lipid metabolism. Mice were treated for
      3 d with leptin, either centrally [intracerebroventricular (icv)] or peripherally
      (ip), and compared with mice pair-fed to the leptin-treated mice (PF) and with ad
      libitum-fed controls (C). All treatment groups (icv, ip, PF) showed
      indistinguishable changes in liver weight; hepatic steatosis; hepatic lipidemic
      profile; and circulating free fatty acids, triglycerides, and cholesterol
      lipoprotein profile. Changes in the expression of genes involved in lipogenesis
      and fatty acid oxidation in liver, muscle, and white fat were broadly similar in
      ip, icv, and PF groups. Leptin (both icv and ip) stimulated expression of both
      mitochondrial and peroxisomal acyl-coenzyme A oxidase (liver) and peroxisomal
      proliferator-activated receptor-alpha (skeletal muscle) to an extent not
      replicated by pair feeding. Leptin had profound effects on peripheral lipid
      metabolism, but the majority were explained by its effects on food intake. Leptin
      had additional centrally mediated effects to increase the expression of a limited
      number of genes concerned with fatty acid oxidation. Whereas we cannot exclude
      direct peripheral effects of leptin on certain aspects of lipid metabolism, we
      were unable to detect any such effects on the parameters measured in this study.

PMID- 18635660
TI  - Expression of Src homology 2 domain-containing protein tyrosine phosphatase
      substrate-1 in pancreatic beta-Cells and its role in promotion of insulin
      secretion and protection against diabetes.
AB  - Insulin secretion by beta-cells of pancreatic islets is regulated by various
      soluble factors including glucose and hormones. The importance of direct cell
      cell communication among beta-cells or between beta-cells and other cell types
      for such regulation has remained unclear, however. Transmembrane proteins Src
      homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1)
      and its ligand CD47 interact through their extracellular regions and contribute
      to intercellular communication. We now show that both SHPS-1 and CD47 are
      prominently expressed in beta-cells of the pancreas. The plasma insulin level in
      the randomly fed state was markedly reduced in mice that express a mutant form of
      SHPS-1 lacking most of the cytoplasmic region compared with that in wild-type
      (WT) mice, although the blood glucose concentrations of the two types of mice
      were similar. This reduction in the plasma insulin level of SHPS-1 mutant mice
      was even more pronounced in animals maintained on a high-fat diet. Glucose
      tolerance was also markedly impaired in SHPS-1 mutant mice on a high-fat diet,
      whereas both peripheral insulin sensitivity and the insulin content of the
      pancreas in the mutant animals were similar to those of WT mice. Glucose
      stimulated insulin secretion was similar for islets isolated from WT or SHPS-1
      mutant mice. The impaired glucose tolerance of SHPS-1 mutant mice was ameliorated
      by treatment with the alpha2-adrenergic antagonist yohimbine. These results
      suggest that SHPS-1 promotes insulin secretion from beta-cells and thereby
      protects against diabetes. Preventing of alpha2-adrenergic receptor-mediated
      inhibition of insulin secretion may partly participate in such a function of SHPS
      1.

PMID- 18635661
TI  - Osteitis fibrosa is mediated by Platelet-Derived Growth Factor-A via a
      phosphoinositide 3-kinase-dependent signaling pathway in a rat model for chronic
      hyperparathyroidism.
AB  - Abnormal secretion of PTH by the parathyroid glands contributes to a variety of
      common skeletal disorders. Prior studies implicate platelet-derived growth factor
      A (PDGF-A) as an important mediator of selective PTH actions on bone. The present
      studies used targeted gene profiling and small-molecule antagonists directed
      against candidate gene products to elucidate the roles of specific PTH-regulated
      genes and signaling pathways. A group of 29 genes in rats continuously infused
      with PTH and cotreated with the PDGF receptor antagonist trapidil were
      differentially expressed compared with PTH treatment alone. Several of the
      identified genes were functionally clustered as regulators of fibroblast
      differentiation and extracellular matrix modeling, including the matrix cross
      linking enzyme lysyl oxidase (LOX). Treatment with beta-aminopropionitrile, an
      irreversible inhibitor of LOX activity, dramatically reduced diffuse
      mineralization but had no effect on PTH-induced fibrosis. In contrast, the
      receptor tyrosine kinase inhibitor Gleevec and the phosphoinositide 3-kinase
      inhibitor wortmannin each reduced bone marrow fibrosis. In summary, the present
      studies support the hypotheses that PTH-induced bone marrow fibrosis is mediated
      by PDGF-A via a phosphoinositide 3-kinase-dependent signaling pathway and that
      increased LOX gene expression plays a key role in abnormal mineralization, a
      hallmark of chronic hyperparathyroidism.

PMID- 18635662
TI  - Developmental regulation and function of thyroid hormone receptors and 9-cis
      retinoic acid receptors during Xenopus tropicalis metamorphosis.
AB  - Amphibian metamorphosis serves as an excellent model to study T3 function during
      postembryonic development in vertebrate due to its total dependence on T3.
      Earlier molecular studies in the model species Xenopus laevis have led to a
      number of important in vivo findings on the function and mechanisms of T3
      receptor (TR) action during vertebrate development. However, the lack of genomic
      sequence information, its tetraploid genome, and lengthy developmental cycle
      hinder further analyses on TR functions. In this regard, the highly related
      species, Xenopus tropicalis, is much more advantageous. Toward developing X.
      tropicalis for genome-wide and genetic studies of TR function, we analyzed the
      expression profiles of TRs and their heterodimerization partners, retinoid X
      receptors (RXRs) or 9-cis retinoic acid receptors. We show that their expression
      correlates with transformations in different organs and that TR/RXR heterodimers
      are capable of repressing and activating gene expression in vivo in the absence
      and presence of T3, respectively. We further demonstrate that TRs are bound to
      endogenous target genes in X. tropicalis tadpoles. Our results thus support a
      role of TRs in mediating the metamorphic effects of T3 in X. tropicalis. More
      importantly, the similarities in the expression and function between X.
      tropicalis and X. laevis TRs and RXRs as demonstrated by our study also pave the
      way to take advantages of existing morphological, molecular, and cellular
      knowledge of X. laevis development and the genetic and sequence superiority of X.
      tropicalis to dissect the molecular pathways governing tissue/organ-specific
      transformations during vertebrate postembryonic development.

PMID- 18635663
TI  - Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss
      by the type 2 cannabinoid receptor.
AB  - The endocannabinoid system has recently been shown to play a role in the
      regulation of bone metabolism. The type 2 cannabinoid receptor (CB2) has been
      reported to regulate bone mass, but conflicting results have been reported with
      regard to its effects on bone resorption and osteoclast function. Here we
      investigated the role that CB2 plays in regulating bone mass and osteoclast
      function using a combination of pharmacological and genetic approaches. The CB2
      selective antagonist/inverse agonist AM630 inhibited osteoclast formation and
      activity in vitro, whereas the CB2-selective agonists JWH133 and HU308 stimulated
      osteoclast formation. Osteoclasts generated from CB2 knockout mice (CB2-/-) were
      resistant to the inhibitory effects of AM630 in vitro, consistent with a CB2
      mediated effect. There was no significant difference in peak bone mass between
      CB2-/- mice and wild-type littermates, but after ovariectomy, bone was lost to a
      greater extent in wild-type compared with CB2-/- mice. Furthermore, AM630
      protected against bone loss in wild-type mice, but the effect was blunted in CB2
      /- mice. We conclude that CB2 regulates osteoclast formation and bone resorption
      in vitro and that under conditions of increased bone turnover, such as after
      ovariectomy, CB2 regulates bone loss. These observations indicate that CB2
      regulates osteoclast formation and contributes to ovariectomy-induced bone loss
      and demonstrate that cannabinoid receptor antagonists/inverse agonists may be of
      value in the treatment of bone diseases characterized by increased osteoclast
      activity.

PMID- 18635664
TI  - Environmental-like exposure to low levels of estrogen affects sexual behavior and
      physiology of female rats.
AB  - Xenoestrogens are endocrine-disrupting chemicals that mimic the action of
      endogenous estrogen hormones. Effects of xenoestrogen on aquatic wildlife are
      well documented, whereas the experimental evidence for impairment of reproductive
      behavior and physiology in mammals after exposure to xenoestrogens has been
      debated. The strongest arguments against such studies have been that the route,
      time course, and intensity of exposure did not simulate environmental exposure
      and that the chemicals tested have additional nonestrogenic toxic effects,
      hindering generalization of actual xenoestrogenic effects. Here we show that
      environmental-like exposure to the pure estrogen 17alpha-ethinylestradiol during
      development alters reproductive behavior and physiology in adult female Sprague
      Dawley rats. We simulated environmental exposure by giving low doses (0.4 and
      0.004 microg/kg.d) of 17alpha-ethinylestradiol orally to pregnant females from
      conception to weaning of the pups, which continued to receive the treatment until
      puberty. We studied the sexual behavior, estrous cycle, and estradiol plasma
      levels of intact female rats when they reached 3 months of age. Exposure to the
      higher dose strongly affected female sexual behavior and physiology, with
      suppression of lordosis and the estrous cycle and enhanced aggression toward
      males. The lower dose disrupted appetitive components of sexual behavior that
      influence the rate of copulation. Estradiol plasma levels were not affected by
      the treatment. Our study revealed that exposure to low oral doses of a pure
      estrogen during development alters female sexual behavior and physiology. These
      results suggest potential risks of reproductive failure from xenoestrogen
      exposure in realistic ecological conditions.

PMID- 18635665
TI  - The extracellular domain of the growth hormone receptor interacts with
      coactivator activator to promote cell proliferation.
AB  - The presence of GH receptor (GHR) in the cell nucleus correlates with cell
      division, and targeting the GHR to the nucleus results in constitutive
      proliferation and transformation because of increased sensitivity to autocrine
      GH. Here we have sought additional mechanisms that might account for the enhanced
      proliferation seen with nuclear GHR, commencing with a yeast two-hybrid (Y2H)
      screen for interactors with the extracellular domain of the GHR [GH-binding
      protein (GHBP)]. We find that the GHBP is a transcriptional activator in yeast
      and mammalian cells, and this activity resides in the lower cytokine receptor
      module. Activity is dependent on S226, the conserved serine of the cytokine
      receptor consensus WSXWS box. By using parallel GHBP affinity columns and tandem
      mass spectrometry of tryptic digests of proteins bound to wild-type GHBP and
      S226A columns, we identified proteins that bind to the transcriptionally active
      GHBP. These include a nucleoporin and two transcriptional regulators, notably the
      coactivator activator (CoAA), which is also an RNA binding splicing protein.
      Binding of CoAA to the GHBP was confirmed by glutathione S-transferase pulldown
      and coimmunoprecipitation, and shown to be GH dependent in pro-B Ba/F3 cells.
      Importantly, stable expression of CoAA in Ba/F3 cells resulted in an increased
      maximum proliferation in response to GH, but not IL-3. Because CoAA
      overexpression has been identified in many cancers and its stable expression
      promotes cell proliferation and cell transformation in NIH-3T3 cells, we suggest
      CoAA contributes to the proliferative actions of nuclear GHR by the hormone
      dependent recruitment of this powerful coactivator to the GHR.

PMID- 18635666
TI  - Analysis of the calcium-dependent regulation of proline-rich tyrosine kinase 2 by
      gonadotropin-releasing hormone.
AB  - Calcium influx through L-type voltage-gated calcium channels (VGCC) is required
      for ERK activation induced by GnRH in pituitary gonadotropes. The current studies
      investigate VGCC-sensitive catalytic activities that may lie upstream of ERKs
      within the GnRH signaling network. Ion exchange fractionation of alphaT3-1 cell
      lysates subjected to anti-phosphotyrosine Western blot analysis revealed a
      nifedipine-sensitive activity that colocalized with proline-rich tyrosine kinase
      (Pyk) 2 immunoreactivity. Phosphorylated Pyk2 was present in alphaT3-1 cells
      after GnRH agonist administration for a time course that lasted up to 4 h. Pyk2
      phosphorylation was also evident in gonadotropes in vivo after administration of
      a bolus of GnRH. Knockdown of Pyk2 using specific small interfering RNAs revealed
      that Pyk2 contributed to modulation of GnRH-induced ERK but not c-Jun N-terminal
      kinase activation. Using pharmacological approaches, calmodulin (Cam) was also
      demonstrated to be required for the phosphorylation of Pyk2. Pyk2 was shown to
      bind specifically to a Cam agarose affinity column in a calcium-dependent manner,
      suggesting Cam and Pyk2 are capable of forming a complex. Specific mutation of a
      putative Cam binding motif within the catalytic domain of Pyk2 blocked
      association with Cam and uncoupled Pyk2's ability to activate ERK-dependent gene
      transcription. Thus, GnRH induces Pyk2 tyrosine phosphorylation dependent upon
      calcium flux within gonadotropes. Furthermore, association of Pyk2 and Cam may be
      required to mediate the effects of calcium on Pyk2 phosphorylation and subsequent
      activation of ERKs by GnRH.

PMID- 18635667
TI  - Splice variant-dependent regulation of beta-cell sodium-calcium exchange by acyl
      coenzyme As.
AB  - The sodium-calcium exchanger isoform 1 (NCX1) is intimately involved in the
      regulation of calcium (Ca(2+)) homeostasis in many tissues including excitation
      secretion coupling in pancreatic beta-cells. Our group has previously found that
      intracellular long-chain acyl-coenzyme As (acyl CoAs) are potent regulators of
      the cardiac NCX1.1 splice variant. Despite this, little is known about the
      biophysical properties of beta-cell NCX1 splice variants and the effects of
      intracellular modulators on their important physiological function in health and
      disease. Here, we show that the forward-mode activity of beta-cell NCX1 splice
      variants is differentially modulated by acyl-CoAs and is dependent both upon the
      intrinsic biophysical properties of the particular NCX1 splice variant as well as
      the side chain length and degree of saturation of the acyl-CoA moiety. Notably,
      saturated long-chain acyl-CoAs increased both peak and total NCX1 activity,
      whereas polyunsaturated long-chain acyl-CoAs did not show this effect.
      Furthermore, we have identified the exon within the alternative splicing region
      that bestows sensitivity to acyl-CoAs. We conclude that the physiologically
      relevant forward-mode activity of NCX1 splice variants expressed in the
      pancreatic beta-cell are sensitive to acyl-CoAs of different saturation and
      alterations in intracellular acyl-CoA levels may ultimately lead to defects in
      Ca(2+)-mediated exocytosis and insulin secretion.

PMID- 18635668
TI  - Selective inhibition of mitogen-activated protein kinase phosphatases by zinc
      accounts for extracellular signal-regulated kinase 1/2-dependent oxidative
      neuronal cell death.
AB  - Oxidative stress induced by glutathione depletion in the mouse HT22 neuroblastoma
      cell line and embryonic rat immature cortical neurons causes a delayed, sustained
      activation of extracellular signal-regulated kinase (ERK) 1/2, which is required
      for cell death. This sustained activation of ERK1/2 is mediated primarily by a
      selective inhibition of distinct ERK1/2-directed phosphatases either by enhanced
      degradation (i.e., for mitogen-activated protein kinase phosphatase-1) or as
      shown here by reductions in enzymatic activity (i.e., for protein phosphatase
      type 2A). The inhibition of ERK1/2 phosphatases in HT22 cells and immature
      neurons subjected to glutathione depletion results from oxidative stress because
      phosphatase activity is restored in cells treated with the antioxidant butylated
      hydroxyanisole. This leads to reduced ERK1/2 activation and neuroprotection.
      Furthermore, an increase in free intracellular zinc that accompanies glutathione
      induced oxidative stress in HT22 cells and immature neurons contributes to
      selective inhibition of ERK1/2 phosphatase activity and cell death. Finally,
      ERK1/2 also functions to maintain elevated levels of zinc. Thus, the elevation of
      intracellular zinc within neurons subjected to oxidative stress can trigger a
      robust positive feedback loop operating through activated ERK1/2 that rapidly
      sets into motion a zinc-dependent pathway of cell death.

PMID- 18635669
TI  - Inhibition of tumor growth by endohedral metallofullerenol nanoparticles
      optimized as reactive oxygen species scavenger.
AB  - Intraperitoneal injection of [Gd@C82(OH)22]n nanoparticles decreased activities
      of enzymes associated with the metabolism of reactive oxygen species (ROS) in the
      tumor-bearing mice. Several physiologically relevant ROS were directly scavenged
      by nanoparticles, and lipid peroxidation was inhibited in this study.
      [Gd@C82(OH)22]n nanoparticles significantly reduced the electron spin resonance
      (ESR) signal of the stable 2,2-diphenyl-1-picryhydrazyl radical measured by ESR
      spectroscopy. Like-wise, studies using ESR with spin-trapping demonstrated
      efficient scavenging of superoxide radical anion, hydroxyl radical, and singlet
      oxygen (1O2) by [Gd@C82(OH)22]n nanoparticles. In vitro studies using liposomes
      prepared from bovine liver phosphatidylcholine revealed that nanoparticles also
      had a strong inhibitory effect on lipid peroxidation. Consistent with their
      ability to scavenge ROS and inhibit lipid peroxidation, we determined that
      [Gd@C82(OH)22]n nanoparticles also protected cells subjected in vitro to
      oxidative stress. Studies using human lung adenocarcinoma cells or rat brain
      capillary endothelial cells demonstrated that [Gd@C82(OH)22]n nanoparticles
      reduced H2O2-induced ROS formation and mitochondrial damage. [Gd@C82(OH)22]n
      nanoparticles efficiently inhibited the growth of malignant tumors in vivo. In
      summary, the results obtained in this study reveal antitumor activities of
      [Gd@C82(OH)22]n nanoparticles in vitro and in vivo. Because ROS are known to be
      implicated in the etiology of a wide range of human diseases, including cancer,
      the present findings demonstrate that the potent inhibition of [Gd@C82(OH)22]n
      nanoparticles on tumor growth likely relates with typical capacity of scavenging
      reactive oxygen species.

PMID- 18635670
TI  - A description of the trials, reviews, and practice guidelines indexed in the
      PEDro database.
AB  - This perspective provides an overview of the randomized controlled trials,
      systematic reviews, and evidence-based clinical practice guidelines in physical
      therapy. Data from the Physiotherapy Evidence Database (PEDro) are used to
      describe key events in the history of physical therapy research and the growth of
      evidence of effects of interventions used in the various subdisciplines of
      physical therapy. The 11,494 records that were identified reveal a rich history
      of physical therapy research dating back to the first trial in 1929. Most of the
      randomized controlled trials, systematic reviews, and evidence-based clinical
      practice guidelines in physical therapy have been published since the year 2000.
      This rapid growth presents a challenge for physical therapists who want to keep
      up to date in clinical practice.

PMID- 18635671
TI  - After partial knee replacement, patients can kneel, but they need to be taught to
      do so: a single-blind randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Kneeling is an important functional activity frequently
      not performed after knee replacement, thus affecting a patient's ability to carry
      out basic daily tasks. Despite no clinical reason preventing kneeling, many
      patients fail to resume this activity. The purpose of this study was to determine
      whether a single physical therapy intervention would improve patient-reported
      kneeling ability following partial knee replacement (PKR). SUBJECTS: Sixty adults
      with medial compartment osteoarthritis, suitable for a PKR, participated.
      METHODS: This was a single-blind, prospective randomized controlled trial. Six
      weeks after PKR, participants randomly received either kneeling advice and
      education or routine care where no specific kneeling advice was given.
      Reassessment was at 1 year postoperatively. The primary outcome measure was
      patient-reported kneeling ability, as assessed by question 7 of the Oxford Knee
      Score. Other factors associated with kneeling ability were recorded. These
      factors were scar position, numbness, range of flexion, involvement of other
      joints, and pain. Statistical analysis included nonparametric tests and binary
      logistic regression. RESULTS: A significant improvement in patient-reported
      kneeling ability was found at 1 year postoperatively in those participants who
      received the kneeling intervention. Group allocation was the only factor
      determining an improvement in patient-reported kneeling ability at 1 year
      postoperatively. DISCUSSION AND CONCLUSION: The single factor that predicted
      patient-reported kneeling ability at 1 year postoperatively was the physical
      therapy kneeling intervention given at 6 weeks after PKR. The results of this
      study suggest that advice and instruction in kneeling should form part of a
      postoperative rehabilitation program after PKR. The results can be applied only
      to patients following PKR.

PMID- 18635672
TI  - Time series analysis of spontaneous upper-extremity movements of premature
      infants with brain injuries.
AB  - BACKGROUND AND PURPOSE: Comparisons of spontaneous movements of premature infants
      with brain injuries and those without brain injuries can provide insights into
      normal and abnormal processes in the ontogeny of motor development. In this
      study, the characteristics of spontaneous upper-extremity movements of premature
      infants with brain injuries and those without brain injuries were examined with
      time series analysis. SUBJECTS: Participants were 7 premature infants with brain
      injuries and 7 matched, low-risk, premature infants at the age of 1 month after
      term. METHODS: A triaxial accelerometer was used to measure upper-extremity limb
      acceleration in 3-dimensional space. Acceleration signals were recorded from the
      right wrist when the infant was in an active, alert state and lying in the supine
      position. The recording time was 200 seconds. The acceleration signal was sampled
      at a rate of 200 Hz. The acceleration time series data were analyzed by nonlinear
      analysis as well as linear analysis. RESULTS: The nonlinear time series analysis
      indicated that spontaneous movements of premature infants have nonlinear,
      chaotic, dynamic characteristics. The movements of the infants with brain
      injuries were characterized by larger dimensionality, and they were more unstable
      and unpredictable than those of infants without brain injuries. DISCUSSION AND
      CONCLUSION: As determined by nonlinear analysis, the spontaneous movements of the
      premature infants with brain injuries had the characteristics of increased
      disorganization compared with those of the infants without brain injuries.
      Infants with brain injuries may manifest problems with self-organization as a
      function of the coordination of subsystems. Physical therapists should be able to
      support interactions among the subsystems and promote self-organization of motor
      learning through the individualized provision of various sensorimotor experiences
      for infants.

PMID- 18635673
TI  - Mutations of CXorf6 are associated with a range of severities of hypospadias.
AB  - OBJECTIVE: Mutations in chromosome X open reading frame 6 (CXorf6), a recently
      described candidate gene involved in the development of male genitalia, have been
      found in patients with complex 46,XY disorders of sexual development (46,XY DSD)
      including micropenis, bifid scrotum, and penoscrotal hypospadias. The objective
      of this work was to identify genomic variants of CXorf6 in patients with isolated
      hypospadias, severe or non-severe. DESIGN AND METHODS: Forty-one patients with
      glandular to perineal hypospadias and thirty controls were studied. Direct
      sequencing for coding exons 3-6 of CXorf6 and their flanking splice sites was
      performed on DNA extracted from foreskin collected from surgery. Secondary and
      tertiary structures of the protein were predicted using NNpredict and Protein
      Homology/analogY Recognition Engine engines. RESULTS: Four mutations (9.7% of
      cases) were identified. One missense mutation (1295T>C, V432A) and two deletions
      (325delG, predicted to cause a stop codon L121X) occurred in patients with
      penoscrotal and proximal hypospadias. One patient with subcoronal hypospadias had
      CAG-repeat amplification in the second polyglutamine domain of CXorf6. Secondary
      structure prediction indicated that this insertion occurred in a helix element of
      the protein. The tertiary structure prediction showed an alteration of the shape
      of the protein and crowding between domains. CONCLUSION: CXorf6 mutations are
      associated with isolated hypospadias of varying severity. However, the
      pathophysiology of these mutations and the function of the CXorf6 gene product
      remain to be investigated.

PMID- 18635674
TI  - Sensorimotor gating of schizophrenia patients depends on Catechol O
      methyltransferase Val158Met polymorphism.
AB  - It has been recently shown that Catechol O-methyltransferase (COMT) Val(158)Met
      polymorphism strongly influences prepulse inhibition (PPI) of the acoustic
      startle response (ASR) in healthy human volunteers. Given that schizophrenia
      patients exhibit impairment in PPI and that COMT is a putative susceptibility
      gene for schizophrenia, we investigated the impact of the COMT Val(158)Met
      polymorphisms on PPI in schizophrenic inpatients. We analyzed COMT Val(158)Met
      polymorphisms and assessed startle reactivity, habituation, and PPI of ASR in 68
      Caucasian schizophrenia inpatients. Clinical symptoms were measured with the
      Positive and Negative Syndrome Scale (PANSS). Patients carrying the Val(158)Met
      Met/Met allele showed elevated PPI levels whereas startle reactivity and
      habituation did not differ from the other two genotypes. These preliminary
      results imply that PPI is influenced by COMT Val(158)Met genotype in
      schizophrenia as well. In concert with other findings, our data suggest that PPI
      is a polygenic trait.

PMID- 18635676
TI  - Schizophrenia and alterations in self-experience: a comparison of 6 perspectives.
AB  - Contemporary researchers have tended to examine dysfunction among the lives of
      persons with schizophrenia as a matter of the impact of biological and social
      forces. While this has greatly advanced the knowledge base, any account of
      schizophrenia without a full consideration of the illness's first-person
      dimensions risks missing that schizophrenia is a disorder that interrupts the
      lives of people who must continue to struggle to find and create security and
      meaning. While literature from a range of sources has explored self-experience in
      schizophrenia, one barrier to the creation of a larger synthesis and application
      of this work is that it remains unclear whether, and to what degree, these
      differing views of self-experience are comparable with one another. To address
      this issue, this article reviews 6 different accounts of self-experience, a
      fundamental, first-person dimension of schizophrenia. The 6 are early psychiatry,
      existential psychiatry, psychoanalysis, phenomenology, psychosocial
      rehabilitation, and dialogical psychology. After comparing and contrasting the 6,
      we conclude that there is a wide-ranging, if general consensus, which suggests
      that many suffering from schizophrenia experience themselves as diminished
      relative to their former selves, ie, after onset they experience themselves as
      less able to engage the world effectively, which intensifies their anxieties in
      the face of everyday interactions. However, within this broad consensus,
      significant disagreements exist around issues such as whether these difficulties
      meaningfully predate the illness, how recovery is possible, and if so, under what
      conditions. In closing, we suggest a program of research to address these
      disagreements.

PMID- 18635677
TI  - Evidence of adaptive evolution of accessory gland proteins in closely related
      species of the Drosophila repleta group.
AB  - Accessory gland proteins (Acps) are part of the seminal fluid of Drosophila
      species. These proteins have important reproductive functions, being responsible
      for the proper functioning of several steps of the fertilization process. Acps
      also contribute indirectly for the reproductive success of males by modulating
      female behavior. Evidence that Acps participate in sperm competition and sexual
      conflict includes findings that, on average, Acps have fast evolutionary rates,
      suggestive of adaptive evolution. This is especially true in species of the
      Drosophila repleta group. Nevertheless, only in a few occasions have robust
      statistical tests been used to determine whether observed evolutionary rates are
      in fact due to positive selection on amino acid substitutions between related
      species. Here we apply maximum likelihood tests for positive selection on 14 Acps
      of the D. repleta group. To increase statistical robustness, we use at least 8
      sequences, all belonging to species of the Drosophila mulleri complex, for each
      gene analyzed. We found significant evidence of adaptive evolution for 10 of the
      tested genes. Among these, the ones with a conserved protein domain had
      positively selected sites within the functional region of the sequence. We also
      detected one instance of lineage-specific adaptive evolution in a clade formed by
      2 sister species.

PMID- 18635675
TI  - Gene-environment interaction and covariation in schizophrenia: the role of
      obstetric complications.
AB  - While genetic factors account for a significant proportion of liability to
      schizophrenia, a body of evidence attests to a significant environmental
      contribution. Understanding the mechanisms through which genetic and
      environmental factors coalesce in influencing schizophrenia is critical for
      elucidating the pathways underlying psychotic illness and for developing primary
      prevention strategies. Although obstetric complications (OCs) remain among the
      most well-documented environmental indicators of risk for schizophrenia, the
      pathogenic role they play in the etiology of schizophrenia continues to remain
      poorly understood. A question of major importance is do these factors result from
      a genetic diathesis to schizophrenia (as in gene-environment covariation), act
      additively or interactively with predisposing genes for the disorder in
      influencing disease risk, or independently cause disease onset? In this review,
      we evaluate 3 classes of OCs commonly related to schizophrenia including hypoxia
      associated OCs, maternal infection during pregnancy, and maternal stress during
      pregnancy. In addition, we discuss several mechanisms by which OCs impact on
      genetically susceptible brain regions, increasing constitutional vulnerability to
      neuromaturational events and stressors later in life (ie, adolescence), which may
      in turn contribute to triggering psychosis.

PMID- 18635678
TI  - Cilium evolution: identification of a novel protein, nematocilin, in the
      mechanosensory cilium of Hydra nematocytes.
AB  - The cnidocil at the apical end of Hydra nematocytes is a mechanosensory cilium,
      which acts as a "trigger" for discharge of the nematocyst capsule. The cnidocil
      protrudes from the center of the cnidocil apparatus and is composed of singlet
      and doublet microtubules surrounding an electron-dense central filament. In this
      paper, we identify a novel protein, nematocilin, which is localized in the
      central filament. Immunofluorescence staining and immunogold electron microscopy
      show that nematocilin forms filaments in the central core of the cnidocil.
      Nematocilin represents a new member of the intermediate filament superfamily. Two
      paralogous sequences of nematocilin are present in the Hydra genome and appear to
      be the result of recent gene duplication. Comparison of the exon-intron structure
      suggests that the nematocilin genes evolved from the nuclear lamin gene by
      conserving exons encoding the coiled-coil domains and replacing the C-terminal
      lamin domains. Molecular phylogenetic analyses also support the hypothesis of a
      common ancestor between lamin and nematocilin. Comparison of cnidocil structures
      in different cnidarians indicates that a central filament is present in the
      cnidocils of several hydrozoan and a cubozoan species but is absent in the
      cnidocils of anthozoans. A nematocilin homolog is absent in the recently
      completed genome of the anthozoan Nematostella. Thus, the evolution of a novel
      ciliary structure, which provides mechanical rigidity to the sensory cilium
      during the process of mechanoreception, is associated with the evolution of a
      novel protein.

PMID- 18635679
TI  - The evolution of the flagellar assembly pathway in endosymbiotic bacterial
      genomes.
AB  - Genome shrinkage is a common feature of most intracellular pathogens and
      symbionts. Reduction of genome sizes is among the best-characterized evolutionary
      ways of intracellular organisms to save and avoid maintaining expensive redundant
      biological processes. Endosymbiotic bacteria of insects are examples of
      biological economy taken to completion because their genomes are dramatically
      reduced. These bacteria are nonmotile, and their biochemical processes are
      intimately related to those of their host. Because of this relationship, many of
      the processes in these bacteria have been either lost or have suffered massive
      remodeling to adapt to the intracellular symbiotic lifestyle. An example of such
      changes is the flagellum structure that is essential for bacterial motility and
      infectivity. Our analysis indicates that genes responsible for flagellar assembly
      have been partially or totally lost in most intracellular symbionts of gamma
      Proteobacteria. Comparative genomic analyses show that flagellar genes have been
      differentially lost in endosymbiotic bacteria of insects. Only proteins involved
      in protein export within the flagella assembly pathway (type III secretion system
      and the basal body) have been kept in most of the endosymbionts, whereas those
      involved in building the filament and hook of flagella have only in few instances
      been kept, indicating a change in the functional purpose of this pathway. In some
      endosymbionts, genes controlling protein-export switch and hook length have
      undergone functional divergence as shown through an analysis of their
      evolutionary dynamics. Based on our results, we suggest that genes of flagellum
      have diverged functionally as to specialize in the export of proteins from the
      bacterium to the host.

PMID- 18635680
TI  - OEM's impact factor reaches a new high.

PMID- 18635681
TI  - Psychological stress of parents of preterm infants enrolled in an early discharge
      programme from the neonatal intensive care unit: a prospective randomised trial.
AB  - BACKGROUND: Psychological stress of parents of preterm infants is aggravated by
      prolonged hospitalisation. Early discharge programmes (EDPs) have been
      implemented to alleviate this situation. OBJECTIVE: To evaluate parental
      psychological stress in an EDP for the first 3 months after neonatal intensive
      care unit (NICU) discharge. DESIGN/METHODS: Prospective randomised trial
      comparing parents of preterm infants assigned to EDP (n = 72) or standard
      discharge programme (SDP) (standard discharge) (n = 68). At discharge, parents
      were evaluated using the Hospital Anxiety and Depression Scale (HAD), and the
      Likert Scale for well-being every 10 days for 3 months. Parental narrative of
      Worrying and Helping issues was assessed using a semi-structured interview.
      RESULTS: Length of stay was greater in the SDP group (p<0.01). HAD showed no
      differences in anxiety, but SDP mothers scored higher in depression (p<0.05).
      Altogether, parents reported a worrisome emotional condition (EDP 87.2%; SDP
      80%), which decreased at the end of the study (EDP 45.2%; SDP 34.5%). Their
      baby's physical well-being was the most relevant issue in the narrative for
      Worrying and Helping issues at discharge (EDP 69.2%; SDP 67.5%); however, it
      decreased at the end of the study (EDP 22.6%; SDP 24.1%). At discharge, the
      paediatrician's support was more for the SDP group. No differences on the Well
      Being Scale were found, but the EDP group always scored better. CONCLUSIONS:
      Vulnerability of parents enrolled in an EDP did not increase after hospital
      discharge. Physical well-being of the baby was the most important issue for both
      groups. EDP parents requested less paediatric support and scored higher in the
      Well-being verbatim.

PMID- 18635682
TI  - Genetic analysis of 56 polymorphisms in 17 genes involved in methionine
      metabolism in patients with abdominal aortic aneurysm.
AB  - BACKGROUND: Previous studies suggested an association between abdominal aortic
      aneurysm (AAA) and hyperhomocysteinaemia, a complex trait determined by genetic
      and environmental factors. Our hypothesis was that polymorphisms in genes
      directly or indirectly involved in methionine metabolism may contribute to AAA
      susceptibility. METHOD: We studied 56 polymorphisms in MTHFR, MTR, MTRR, CBS,
      MTHFD1, SLC19A1, NNMT, TCN2, AHCY, BHMT, BHMT2, FOLH1, TYMS, ENOSF1, SHMT1, PON1,
      PON2 genes according to their demonstrated/putative function, localisation in
      promoter or regulatory and coding regions and/or heterozygosity values >0.300.
      Polymorphisms were evaluated by using a primer extension based microarray
      technology in 423 AAA patients and 423 matched controls. RESULTS: All
      polymorphisms resulted in Hardy-Weinberg equilibrium in patients and controls. At
      the multiple logistic regression analysis adjusted for traditional cardiovascular
      risk factors (sex, age, hypertension, smoking habit, dyslipidaemia, diabetes) and
      chronic obstructive pulmonary disease (COPD), rs8003379 MTHFD1 (odds ratio (OR)
      0.41, 95% confidence interval (CI) 0.26 to 0.65) and rs326118 MTRR (OR 0.47, 95%
      CI 0.29 to 0.77) polymorphisms resulted in independent susceptibility factor for
      AAA. CONCLUSIONS: After haplotype reconstruction, logistic regression analyses
      adjusted for traditional risk factors and COPD showed a significant association
      among AAA and AHCY, FOLH1, MTHFD1, MTR, NNMT, PON1 and TYMS haplotypes. Our
      findings offer new insights into the pathogenesis of AAA.

PMID- 18635683
TI  - Metric adjusted skew information.
AB  - We extend the concept of Wigner-Yanase-Dyson skew information to something we
      call "metric adjusted skew information" (of a state with respect to a conserved
      observable). This "skew information" is intended to be a non-negative quantity
      bounded by the variance (of an observable in a state) that vanishes for
      observables commuting with the state. We show that the skew information is a
      convex function on the manifold of states. It also satisfies other requirements,
      proposed by Wigner and Yanase, for an effective measure-of-information content of
      a state relative to a conserved observable. We establish a connection between the
      geometrical formulation of quantum statistics as proposed by Chentsov and
      Morozova and measures of quantum information as introduced by Wigner and Yanase
      and extended in this article. We show that the set of normalized Morozova
      Chentsov functions describing the possible quantum statistics is a Bauer simplex
      and determine its extreme points. We determine a particularly simple skew
      information, the "lambda-skew information," parametrized by a lambda in (0, 1],
      and show that the convex cone this family generates coincides with the set of all
      metric adjusted skew informations.

PMID- 18635684
TI  - The finite harmonic oscillator and its associated sequences.
AB  - A system of functions (signals) on the finite line, called the oscillator system,
      is described and studied. Applications of this system for discrete radar and
      digital communication theory are explained.

PMID- 18635685
TI  - Exact subgrid interface correction schemes for elliptic interface problems.
AB  - We introduce a nonconforming finite-element method for second order elliptic
      interface problems. Our approach applies to problems in which discontinuous
      coefficients and singular sources on the interface may give rise to jump
      discontinuities in either the solution or its normal derivative. Given a standard
      background mesh and an interface that passes between elements, the key idea is to
      construct a singular correction function that satisfies the prescribed jump
      conditions, providing accurate subgrid resolution of the discontinuities.
      Utilizing the closest point extension and an implicit interface representation by
      the signed distance function, an algorithm is established to construct the
      correction function. The result is a function that is supported only on the
      interface elements, represented by the regular basis functions, and bounded
      independently of the interface location with respect to the background mesh. In
      the particular case of a constant second-order coefficient, our regularization by
      a singular function is straightforward, and the resulting left-hand side is
      identical to that of a regular problem without introducing any instability. The
      influence of the regularization appears solely on the right-hand side, which
      simplifies the implementation. In the more general case of discontinuous second
      order coefficients, a normalization is invoked which introduces a constraint
      equation on the interface. This results in a problem statement similar to that of
      a saddle-point problem. We employ two-level iteration as the solution strategy,
      which exhibits aspects similar to those of iterative preconditioning strategies.

PMID- 18635686
TI  - Proteome-wide characterization of sugarbeet seed vigor and its tissue specific
      expression.
AB  - Proteomic analysis of mature sugarbeet seeds led to the identification of 759
      proteins and their specific tissue expression in root, cotyledons, and perisperm.
      In particular, the proteome of the perispermic storage tissue found in many seeds
      of the Caryophyllales is described here. The data allowed us to reconstruct in
      detail the metabolism of the seeds toward recapitulating facets of seed
      development and provided insights into complex behaviors such as germination. The
      seed appears to be well prepared to mobilize the major classes of reserves (the
      proteins, triglycerides, phytate, and starch) during germination, indicating that
      the preparation of the seed for germination is mainly achieved during its
      maturation on the mother plant. Furthermore, the data revealed several pathways
      that can contribute to seed vigor, an important agronomic trait defined as the
      potential to produce vigorous seedlings, such as glycine betaine accumulation in
      seeds. This study also identified several proteins that, to our knowledge, have
      not previously been described in seeds. For example, the data revealed that the
      sugarbeet seed can initiate translation either through the traditional cap
      dependent mechanism or by a cap-independent process. The study of the tissue
      specificity of the seed proteome demonstrated a compartmentalization of metabolic
      activity between the roots, cotyledons, and perisperm, indicating a division of
      metabolic tasks between the various tissues. Furthermore, the perisperm, although
      it is known as a dead tissue, appears to be very active biochemically, playing
      multiple roles in distributing sugars and various metabolites to other tissues of
      the embryo.

PMID- 18635687
TI  - Silicon-Carbon bond cleavage reactions of Ansa tungstenocene compounds: the
      [Me2Si] bridge as a site for metallocene functionalization.
AB  - [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl is obtained via reaction of WCl(6) with a mixture
      of [Me(2)Si(Cp(Me(2)))(2)]Li(2) and NaBH(4), from which the dichloride
      [Me(2)Si(Cp(Me(2)))(2)]WCl(2) is obtained via treatment with CHCl(3).
      [Me(2)Si(Cp(Me(2)))(2)]WCl(2) provides a means to access other ansa tungstenocene
      compounds, such as [Me(2)Si(Cp(Me(2)))(2)]WH(2), [Me(2)Si(Cp(Me(2)))(2)]WMe(2),
      and [Me(2)Si(Cp(Me(2)))(2)]WCO. Of most interest, the reactions of
      [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl with organolithium reagents do not yield simple
      ansa tungstenocene derivatives. Specifically, the reactions of
      [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl with MeLi, Bu(n)Li, or PhLi result in the formation
      of mixed-ring tungstenocene compounds resulting from C-Si cleavage and
      functionalization of the ansa bridge, namely (Cp(Me(2)))(eta(5),kappa(1)
      C(5)H(2)Me(2)SiMe(2)CH(2))WH, (Cp(Me(2)))[eta(5),kappa(1)
      C(5)H(2)Me(2)Si(Me)(Bu(n))CH(2)]WH, and (Cp(Me(2)))[eta(5),kappa(1)
      C(5)H(2)Me(2)SiMe(2)(C(6)H(4))]WH, respectively. In contrast to the C-Si cleavage
      achieved by MeLi, Bu(n)Li, and PhLi, the ansa bridge of
      [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl is inert to Bu(t)Li and the product obtained is the
      fulvene ("tuck-in") complex [Me(2)Si(Cp(Me(2)))(eta(6)-C(5)MeH(2)CH(2))]WH
      derived from dehydrohalogenation.

PMID- 18635688
TI  - Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic
      cells in vitro and actively inhibit their maturation.
AB  - Naturally occurring CD4(+)CD25(+) regulatory T cells (Treg) suppress in vitro the
      proliferation of other T cells in a cell-contact-dependent manner. Dendritic
      cells (DCs) appear to be a target of Treg-mediated immune suppression. We show
      here that, in coculture of dye-labeled Treg cells and CD4(+)CD25(-) naive T cells
      in the presence of T cell receptor stimulation, Treg cells, which are more mobile
      than naive T cells in vitro, out-compete the latter in aggregating around DCs.
      Deficiency or blockade of leukocyte function-associated antigen-1 (LFA-1)
      (CD11a/CD18) abrogates Treg aggregation, whereas that of cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4) (CD152) does not. After forming aggregates, Treg
      cells specifically down-regulate the expression of CD80/86, but not CD40 or class
      II MHC, on DCs in both a CTLA-4- and LFA-1-dependent manner. Notably, Treg exerts
      this CD80/86-down-modulating effect even in the presence of strong DC-maturating
      stimuli, such as GM-CSF, TNF-alpha, IFN-gamma, type I IFN, and
      lipopolysaccharide. Taken together, as a possible mechanism of in vitro Treg
      mediated cell contact-dependent suppression, we propose that antigen-activated
      Treg cells exert suppression by two distinct steps: initial LFA-1-dependent
      formation of Treg aggregates on immature DCs and subsequent LFA-1- and CTLA-4
      dependent active down-modulation of CD80/86 expression on DCs. Both steps prevent
      antigen-reactive naive T cells from being activated by antigen-presenting DCs,
      resulting in specific immune suppression and tolerance.

PMID- 18635689
TI  - Incidence of craving for and abuse of gamma-hydroxybutyric acid (GHB) in
      different populations of treated alcoholics: an open comparative study.
AB  - Gamma-hydroxybutyric acid (GHB) is a drug currently used for the treatment of
      alcohol dependence. The aim of our study was to investigate the incidence of
      craving for and abuse of GHB in 47 patients enrolled and divided into four
      groups: group A (pure alcoholics), group B (alcoholics with a sustained full
      remission from cocaine dependence), group C (alcoholics with a sustained full
      remission from heroin dependence) and group D (alcoholics in a methadone
      maintenance treatment [MMT] programme). All patients were treated with an oral
      dose of GHB (50 mg/kg of body weight t.i.d.) for three months. Craving for GHB
      was statistically significant higher in group B than in group A (P < 0.001), C (P
      = 0.01) and D (P < 0.001), and in group C than in group D (P < 0.05). Abuse of
      GHB proved to be statistically significant higher in group B than in group A (P <
      0.001) and D (P < 0.01), and in group C than in group A (P = 0.01) and D (P <
      0.05). Thus, the administration of GHB in alcoholics with a sustained full
      remission from heroin or cocaine dependence is not recommended; however, this
      should not discourage physicians from using GHB for the treatment of pure
      alcoholics or alcohol dependents following a MMT.

PMID- 18635690
TI  - Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind,
      placebo- and active-comparator controlled evaluation using a dental anxiety
      model.
AB  - To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89
      patients were randomised to double-blind single dose pregabalin 150 mg,
      alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental
      Anxiety Total score >12 (moderate-to-severe) without meeting Diagnostic and
      Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder
      criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h
      postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary
      outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient
      rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model
      analysis found significantly greater VAS-A improvement slopes for pregabalin (t =
      -2.47; P = 0.014) and alprazolam (t = -2.39; P = 0.018). There was a significant
      improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam
      patients and from 3 h onward in pregabalin patients. Pregabalin produced
      significantly greater increases in VAS-Sedation versus placebo from 2.5 h through
      4 h (2 h onward for alprazolam). Notably, there was a higher correlation between
      TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = -0.50) on Spearman's
      analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent
      for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7,
      3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N =
      3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0).
      These results suggest that onset of clinically meaningful anxiolytic effect after
      single-dose pregabalin occurs within the first 3-4 h. Additional research is
      needed to determine whether anxiolytic effect occurs in generalized anxiety
      disorder populations by day 1 or within 3-4 h post-first dose.

PMID- 18635691
TI  - Metabolic syndrome in female patients with schizophrenia treated with second
      generation antipsychotics: a 3-month follow-up.
AB  - The objective of this study was to determine the occurrence of metabolic
      abnormalities among previously unmedicated female patients with Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition schizophrenia spectrum
      disorders and their associations with olanzapine and risperidone treatment. We
      analysed 94 female patients who were treated with olanzapine or risperidone in
      the period of 3 months. Analysed variables included fasting glucose, total
      cholesterol, low-density lipoprotein (LDL), high-density lipoproteins and
      triglycerides in blood, blood pressure (BP), waist and hip circumferences and
      body mass index (BMI). At baseline, 14 patients (15%) fulfilled criteria for
      metabolic syndrome. After 3 months of treatment, 25 patients (27%) fulfilled
      criteria for metabolic syndrome, and their baseline BMI was the only predictor
      for its development. Treatment with both antipsychotics was associated with
      significant increase in waist circumference. Positive family history of diabetes
      mellitus contributed to a significant greater increase in abdominal obesity,
      significant higher baseline levels and a borderline significant increase in
      fasting glucose among olanzapine-treated patients. Olanzapine admission was
      associated with a significant increase in LDL and risperidone with a significant
      increase in triglycerides. Metabolic abnormalities seem to be more prevalent in
      unmedicated female patients with schizophrenia spectrum disorders than expected
      based on results in general population (adjusted for age and sex). Olanzapine
      treatment might induce significant alterations in metabolic profiles, especially
      among patients with positive family history of diabetes, mostly by inducing
      abdominal obesity. The association of risperidone application and increase in
      triglyceride level still needs to be determined.

PMID- 18635692
TI  - Antimanic potency of typical neuroleptic drugs and affinity for dopamine D2 and
      serotonin 5-HT2A receptors--a new analysis of data from the archives and
      implications for improved antimanic treatments.
AB  - Datasets of antimanic potency ratings and receptor-binding affinities [inhibition
      constants (K(i))] at dopamine D2 and serotonin 5-HT2A brain receptors were
      accessed from published literature for a large series (n = 24) of typical
      neuroleptic drugs, many of which are now obsolete and unobtainable. There was a
      strong positive association between antimanic potency and affinity for D2
      receptors, in support of a 'dopamine-blockade hypothesis' of antimanic drug
      action. Taking the series of neuroleptics as a whole, there was no association
      between antimanic potency and affinity for 5-HT2A receptors. Despite this, within
      a subsample of typical neuroleptics with low affinity for D2 receptors resembling
      new generation atypical antipsychotics, a positive association between antimanic
      potency and affinity for 5-HT2A receptors emerged. This suggests that blockade of
      brain 5-HT2A receptors plays at least a subsidiary role in the antimanic effects
      of some typical neuroleptics. Other considerations also suggest that combining
      drugs to achieve high affinity for and blockade of both dopamine D2 receptors and
      serotonin 5-HT2A receptors, possibly with additional direct or indirect
      stimulation of postsynaptic 5-HT1A receptors, might maximize antimanic efficacy.

PMID- 18635693
TI  - Investigation of serotonin-1A receptor function in the human psychopharmacology
      of MDMA.
AB  - Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4
      methylenedioxymethamphetamine (MDMA, 'ecstasy') action in the primate brain.
      Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT2A
      receptors also contributes to the overall action of MDMA. The role of 5-HT1A
      receptors in the human psychopharmacology of MDMA, however, has not yet been
      elucidated. In order to reveal the consequences of manipulation at the 5-HT1A
      receptor system on cognitive and subjective effects of MDMA, a receptor blocking
      study using the mixed beta-adrenoreceptor blocker/5-HT1A antagonist pindolol was
      performed. Using a double-blind, placebo-controlled within-subject design, 15
      healthy male subjects were examined under placebo (PL), 20 mg pindolol (PIN),
      MDMA (1.6 mg/kg b.wt.), MDMA following pre-treatment with pindolol (PIN-MDMA).
      Tasks from the Cambridge Neuropsychological Test Automated Battery were used for
      the assessment of cognitive performance. Psychometric questionnaires were applied
      to measure effects of treatment on core dimensions of Altered States of
      Consciousness, mood and state anxiety. Compared with PL, MDMA significantly
      impaired sustained attention and visual-spatial memory, but did not affect
      executive functions. Pre-treatment with PIN did not significantly alter MDMA
      induced impairment of cognitive performance and only exerted a minor modulating
      effect on two psychometric scales affected by MDMA treatment ('positive
      derealization' and 'dreaminess'). Our findings suggest that MDMA differentially
      affects higher cognitive functions, but does not support the hypothesis from
      animal studies, that some of the MDMA effects are causally mediated through
      action at the 5-HT1A receptor system.

PMID- 18635694
TI  - Olanzapine treatment in Jarisch-Herxheimer reaction due to neurosyphilis with
      dementia: a case report.
AB  - We discussed a neurosyphilis case who had a risky sexual intercourse history
      nearly 10 years ago. After the neurosyphilis diagnosis, the patient has clinical
      symptoms of a demential case starting as a typical manic episode and Jarisch
      Herxheimer reaction because of intravenous penicillin treatment that has improved
      with olanzapine treatment.

PMID- 18635695
TI  - Eight-week, placebo-controlled, double-blind comparison of the antidepressant
      efficacy and tolerability of bupropion XR and venlafaxine XR.
AB  - The efficacy, safety and tolerability of bupropion XR and venlafaxine XR was
      assessed and compared with placebo in adult outpatients with major depressive
      disorder (MDD). Adults meeting DSM-IV criteria for MDD with a minimum Hamilton
      Depression Rating Scale (HAMD) 17-Item total score of > or =18 were randomized to
      eight weeks of double-blind treatment with either bupropion XR (150 mg/day),
      venlafaxine XR (75 mg/day) or placebo. At the end of the fourth week of
      treatment, a dosage increase to bupropion XR 300 mg/day or venlafaxine XR 150
      mg/day was allowed if, in the opinion of the investigator, response was
      inadequate. The primary efficacy endpoint was mean change from baseline at week 8
      in the Montgomery-Asberg Depression Rating Scale (MADRS) total score last
      observation carried forward (LOCF). Mean changes from baseline at week 8 (LOCF)
      in MADRS total score were statistically significant for bupropion XR and
      venlafaxine XR patients compared to the placebo group: -16.0 for bupropion XR (P
      = 0.006 vs placebo), -17.1 for venlafaxine XR (P < 0.001 vs placebo) and -13.5
      for placebo. Secondary outcomes (including CGI-S, HAM-A, MEI, Q-LES-Q-SF,
      responder and remitter analyses) also improved significantly for both active
      treatment groups compared with placebo. The most frequently reported adverse
      events were dry mouth and insomnia for bupropion XR, and nausea, hyperhidrosis,
      fatigue, and insomnia for venlafaxine XR. In this double-blind, placebo
      controlled trial, bupropion XR at doses up to 300 mg/day and venlafaxine XR at
      doses up to 150 mg/day demonstrated comparable antidepressant efficacy.

PMID- 18635696
TI  - The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A alpha2,3
      selective agonist, in comparison with lorazepam in healthy volunteers.
AB  - Benzodiazepines are effective short-term treatments for anxiety disorders, but
      their use is limited by undesirable side effects related to Central Nervous
      System impairment and tolerance development. SL65.1498 is a new compound that
      acts in vitro as a full agonist at the gamma-aminobutyric acid(A) 2 and 3
      receptor and as a partial agonist at the 1 and 5 receptor subtypes. It is thought
      that the compound could be anxiolytic by its activation at the alpha2 and alpha3
      receptor subtypes, without causing unfavourable side effects, which are believed
      to be mediated by the alpha1 and alpha5 subtypes. This study was a double-blind,
      five-way cross-over study to investigate the effects of three doses of SL65.1498
      in comparison with placebo and lorazepam 2 mg in healthy volunteers. The
      objective was to select a dose level (expected to be therapeutically active),
      free of any significant deleterious effect. Psychomotor and cognitive effects
      were measured using a validated battery of measurements, including eye movements,
      body sway, memory tests, reaction-time assessments, and visual analogue scales.
      The highest dose of SL65.1498 showed slight effects on saccadic peak velocity and
      smooth pursuit performance, although to a much lesser extent than lorazepam. In
      contrast to lorazepam, none of the SL65.1498 doses affected body sway, visual
      analogue scale alertness, attention, or memory tests. This study showed that the
      three doses of SL65.1498 were well tolerated and induced no impairments on
      memory, sedation, psychomotor, and cognitive functions.

PMID- 18635697
TI  - D1 receptor antagonist-induced long-term depression in the medial prefrontal
      cortex of rat, in vivo: an animal model of psychiatric hypofrontality.
AB  - The objective of the following experiment was to induce a pathogenic hypofrontal
      condition by administering a dopamine-1 receptor (D(1)R) antagonist to rats. The
      pathophysiological effect of this manipulation upon glutamate-based long-term
      potentiation (LTP) in the medial prefrontal cortex (mPFC) was examined in vivo.
      Subjects were surgically implanted with stimulating electrodes into the corpus
      callosum and recording electrodes into the mPFC. High-frequency stimulation (HFS)
      was combined with the administration of the selective D(1)R family agonist A68930
      hydrochloride (0.4 mg/kg/mL) and the selective D(1)R family antagonist SKF 83566
      (0.15 mg/kg/mL). The administration of SKF 83566 hydrobromide prevented mPFC LTP,
      and resulted in HFS-induced long-term depression. This indicates that D(1)R
      activation is necessary for the induction of mPFC glutamate-based LTP. This is
      supported by our finding that the administration of A68930 hydrochloride combined
      with HFS induced LTP comparable with saline control levels, suggesting that D(1)R
      activation is necessary for the induction of baseline levels of mPFC LTP. Given
      that the mPFC governs executive behaviours that are subserved by LTP, such as
      working memory, these findings are relevant for the study of psychopathological
      conditions in which hypodopaminergic conditions exist in the mPFC and are
      correlated with psychiatric symptomotology, such as drug addiction and
      schizophrenia.

PMID- 18635698
TI  - Attributions for psychobiological changes in ecstasy/MDMA and other polydrug
      users.
AB  - Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] use has been associated with a
      number of psychopathological problems. However, research suggests that reported
      symptoms might be associated more with heavy polydrug use in general rather than
      ecstasy per se. The current study aimed to determine the role of other drug use
      in reports of long-term effects by some ecstasy-polydrug users. Problematic
      ecstasy users (n = 53), reporting problems which they attributed to ecstasy use,
      were compared with non-problematic ecstasy users (n = 62), polydrug (n = 62) and
      alcohol/nicotine using controls (n = 111). Drug use was recorded, and positive
      and negative life changes were assessed along with which previous drug use, if
      any, they attributed these changes too. Both ecstasy groups reported higher drug
      use compared with polydrug controls. Polydrug and ecstasy users more often
      reported life changes compared with non-drug users, and ecstasy users appeared to
      experience more life changes than polydrug users, with problematic ecstasy users
      experiencing most alterations. Ecstasy users reported changes more to a
      combination of drugs than to one specific drug, suggesting that polydrug use in
      these groups has an impact on their life experiences. These findings emphasise
      that research into the psychological effects of ecstasy should not underestimate
      the role of other polydrug use.

PMID- 18635699
TI  - Neural markers of symptomatic improvement during antidepressant therapy in severe
      depression: subgenual cingulate and visual cortical responses to sad, but not
      happy, facial stimuli are correlated with changes in symptom score.
AB  - Resting state activity in the ventral cingulate may be an important neural marker
      of symptomatic improvement in depression. The number of task related functional
      magnetic resonance imaging (fMRI) studies correlating blood oxygenation level
      dependent (BOLD) response with symptomatic improvement is limited and
      methodologies are still evolving. We measured BOLD responses to sad and happy
      facial stimuli in 12 severely depressed individuals in the early stages of
      antidepressant treatment (Time 1) and 12 weeks later (Time 2) using event-related
      fMRI. We calculated correlations between temporal changes in BOLD response and
      changes in symptom scores. Most subjects improved markedly by Time 2. At Time 1,
      depression severity correlated positively with responses to sad stimuli in the
      right visual cortex, subgenual cingulate, anterior temporal pole and hippocampus
      and correlated negatively with responses to happy stimuli in left visual cortex
      and right caudate. Decreases in individual effect sizes of right subgenual
      cingulate and right visual cortical responses to sad, but not happy, facial
      stimuli were correlated with decreases in symptom scores. There are contrasting
      cortical and subcortical responses to sad and happy stimuli in severe depression.
      Responses to sad stimuli show the strongest correlates of clinical improvement,
      particularly in the subgenual cingulate.

PMID- 18635700
TI  - Risk of cerebrovascular events in elderly users of antipsychotics.
AB  - It has been shown that elderly patients with dementia treated with atypical and
      conventional antipsychotics have a twofold increased risk of cerebrovascular
      adverse events (CVAEs). To investigate the temporal relationship between exposure
      to antipsychotics and the risk of CVAE, a case-control analysis nested within a
      cohort of 26,157 community-dwelling patients (mean age 76 +/- 9.7) with at least
      one antipsychotic prescription was conducted. Data were used from Dutch community
      pharmacies and hospital discharge records. Five hundred and eighteen cases of
      hospital admission for CVAE were identified. For each case, four randomly
      selected controls matched by sex and age were sampled from the cohort. To
      evaluate the temporal relationship between antipsychotic use and the occurrence
      of CVAE, two measures were used: the first being a current, recent or past user,
      and the second for the current users, the duration of use up to the index date.
      In addition, the cumulative exposure was assessed. Current and recent exposure to
      antipsychotics were associated with an increased risk of CVAE compared with non
      users (odds ratio [OR] 1.7, CI 1.4-2.2). A strong temporal relationship was
      found; the OR for a history of use less than a week is 9.9 (5.7-17.2). The risk
      decreases in time and is comparable to non-users after 3 months of use (OR 1.0,
      CI 0.7-1.3). Cumulative exposure was not associated with an increase in risk. The
      risk of CVAE in elderly patients associated with antipsychotics is elevated
      especially during the first weeks of treatment. This risk decreases over time and
      is back on base level after 3 months of treatment. Chronic use is not associated
      with CVAE.

PMID- 18635701
TI  - Pharmacological interventions for the prevention of relapse in bipolar disorder:
      a systematic review of controlled trials.
AB  - We conducted a systematic review and meta-analysis of randomised and quasi
      randomised controlled trials evaluating all clinically relevant pharmacological
      interventions for the prevention of relapse in people with bipolar disorder.
      Thirty-four trials were included in the review. Direct comparisons with placebo
      and with lithium were available for most drugs. In addition, there were direct
      comparisons of valproate vs. olanzapine, imipramine vs. lithium plus imipramine,
      olanzapine plus mood stabilisers vs. mood stabilisers and perphenazine plus mood
      stabilisers vs. mood stabilisers. Methodological quality varied across studies
      and the strength of evidence was not equal for all treatments or for all
      comparisons. There is evidence from placebo-controlled trials for the efficacy of
      lithium, valproate and lamotrigine as maintenance therapy for the prevention of
      relapse in bipolar disorder. Three drugs have a significant effect in the
      prevention of manic relapses (lithium, olanzapine and aripiprazole) and three in
      the prevention of depressive symptoms (valproate, lamotrigine and imipramine).
      Imipramine is little used in practice, because of concern about adverse effects.
      The significant effects of olanzapine and aripiprazole were demonstrated in
      selected responsive bipolar I patients only. Despite widespread use in clinical
      practice, there is little evidence to support the efficacy of combination
      therapy.

PMID- 18635702
TI  - Problems associated with long-term treatment with selective serotonin reuptake
      inhibitors.
AB  - Although the selective serotonin reuptake inhibitors (SSRIs), which are now
      widely used as a first-line treatment for depression and many other psychiatric
      conditions, are generally well tolerated, they are not devoid of side effects.
      Most short-term treatment-related side effects of SSRIs are transient and
      disappear after a few days or weeks. However, following long-term treatment with
      the SSRIs, some serious adverse events may occur. Some of them can be difficult
      to recognise because they can resemble residual symptoms of depression. The most
      serious can be life threatening. They all have a negative influence on the
      patient's quality of life and are frequently a prime reason for a lack of long
      term compliance with the associated increased risk of recurrence of a depressive
      episode. This article is an overview of the more common adverse events, which are
      seen with non-acute treatment with the SSRIs.

PMID- 18635703
TI  - Pharmacodynamic and pharmacokinetic effects of the intravenously administered CB1
      receptor agonist Org 28611 in healthy male volunteers.
AB  - CB1/CB2 agonists are reported to have sedative, amnestic, analgesic and anti
      emetic properties, which would make them ideal drugs for outpatient treatments
      under conscious sedation. The main objective of this in human study was to assess
      the sedative properties of Org 28611, a potent water-soluble CB1 agonist. Single
      ascending doses were administered during a slow 25 min infusion and after a 1 min
      bolus administration to healthy male volunteers. In addition, the
      pharmacokinetics, amnestic properties, postural stability, electro
      encephalography, behavioural and cardiovascular effects were studied. Midazolam
      0.1 mg/kg was used as a positive control. The pharmacokinetic parameters were
      proportional to dose. No effects were observed after intravenous administration
      of doses up to Org 28611 1 microg/kg. Dose-related effects were observed at
      higher doses. Although subjects reported subjective sedation after administration
      of Org 28611 3-10 microg/kg, the observed sedation was considerably less than
      after midazolam. Org 28611 is, therefore, not suitable for providing sedation for
      outpatient surgical procedures and doses above the maximum tolerated dose of 3
      microg/kg (either administered as a slow infusion or a bolus dose) can cause
      untoward psychotropic effects.

PMID- 18635704
TI  - Lack of association between AKT1 variances versus clinical manifestations and
      social function in patients with schizophrenia.
AB  - The elucidation of genotype-phenotype relationships in psychiatric research is at
      an early stage. V-akt murine thymoma viral oncogene homolog 1 (AKT1) is a
      serine/threonine kinase known as protein kinase B. Emerging studies have
      implicated the role of AKT1 in pathogenesis of schizophrenia; however, the
      findings have not been consistent. This study aims to examine the association of
      AKT1 polymorphisms with drug-free and post-treatment symptomatology and social
      function in patients with schizophrenia. One hundred and twenty newly
      hospitalised patients with acutely exacerbated schizophrenia who had never been
      treated by atypical antipsychotics were recruited. They received optimal
      treatment of risperidone for up to 42 days in the inpatient research unit.
      Clinical manifestations were monitored by Positive and Negative Syndrome Scale
      (PANSS) and social function by Nurses' Observation Scale for Inpatients
      Evaluation (NOSIE). Patients were genotyped for eight AKT1 Single Nucleotide
      Polymorphism (SNPs), which have been previously investigated for association with
      schizophrenia. At drug-free status and after best possible treatment of
      risperidone, genotypes of each SNP did not influence performances in NOSIE, PANSS
      total, -positive, -negative and -general psychopathology profiles. These results
      suggest that AKT1 does not play a significant role in clinical and functional
      manifestations in patients with schizophrenia who receive risperidone treatment.
      Future research should also focus on the relationships between genotypes of other
      susceptibility genes and phenotypes or functional outcomes of schizophrenia.

PMID- 18635705
TI  - Cholinergic agonism alters cognitive processing and enhances brain functional
      connectivity in patients with multiple sclerosis.
AB  - The aim of this study is to define mechanisms underlying the pharmacological
      effects of brain cholinesterase inhibition on cognitive function in patients with
      multiple sclerosis (MS). Both a Stroop task and an N-back task were used to probe
      the changes in brain activity using functional magnetic resonance imaging (fMRI)
      in a single (investigator)-blind, crossover treatment design studying 15 patients
      with multiple sclerosis (12 relapsing remitting, 3 secondary progressive) taking
      rivastigmine (4.5 mg po bid) and domperidone (10 mg po qd) or domperidone alone.
      Administration of rivastigmine increased Stroop functional magnetic resonance
      imaging activation in the right inferior frontal gyrus for the Stroop task (P <
      0.05, corrected). Incremental functional magnetic resonance imaging activation
      with progressively greater N-back task difficulty was enhanced by rivastigmine in
      prefrontal and parietal cortical regions (P < 0.01, ANOVA). Functional
      connectivity analysis of the N-back functional magnetic resonance imaging data
      based on correlations between pair-wise interregional activations showed
      increased connectivity between left to right prefrontal, anterior cingulate to
      left prefrontal and right parietal to right prefrontal regions with rivastigmine
      (P < 0.05, corrected). Although there were no statistically significant changes
      in the neuropsychological task performance with rivastigmine in this small study,
      11 of 15 patients showed improvements, whereas only 4 of 15 patients showed
      decline in performance (P = 0.07). With regard to the previous data, these
      findings suggest different patterns of brain response to lower dose acute and
      higher dose chronic administration of rivastigmine in patients with multiple
      sclerosis. They showed that rivastigmine enhances the prefrontal function and
      alters the functional connectivity associated with cognition. We interpret this
      as evidence for greater efficiency of brain information transfer that should
      increase confidence in a potentially beneficial clinical therapeutic effect.

PMID- 18635706
TI  - Repeated administrations of dopamine receptor agents affect lithium-induced state
      dependent learning in mice.
AB  - The influence of repeated administration of dopamine receptor agents on the
      effect of lithium on lithium-induced state-dependent learning was examined in
      mice. Immediate post-training intraperitoneal (i.p.) administrations of lithium
      (10 and 20 m/kg) decreased the step-down latency of a single-trial inhibitory
      avoidance task. This was fully or partly reversed by pre-test administration of
      the same doses of the drug, with maximum response at the dose of 10 mg/kg,
      suggesting state-dependent learning was induced by lithium. Here, it has also
      been shown that repeated intracerebroventricular administrations of a mixed D1/D2
      dopamine receptors agonist apomorphine (once daily injections of 0.5 microg/mouse
      for three consecutive days followed by five days of no drug treatment) increased
      the effect of lower doses of pre-test lithium (1.25, 2.5 and 5 mg/kg, i.p.) on
      the reinstatement of the step-down latency decreased by post-training lithium (10
      mg/kg). On the contrary, not only repeated administrations of the dopamine D1
      receptor antagonist SCH 23390 (0.5 and 1 microg/mouse) but also the dopamine D2
      receptor antagonist sulpiride (0.3 and 1 microg/mouse) disrupted the state
      dependent learning induced by lithium. These results suggest that state-dependent
      learning induced by lithium may be altered by repeated pretreatment of dopamine
      receptor agents.

PMID- 18635707
TI  - Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in
      adult stimulant abusers.
AB  - The objective of this study is to determine the safety, tolerability and abuse
      liability of single intravenous (i.v.) doses of lisdexamfetamine dimesylate (LDX)
      and immediate-release d-amphetamine sulphate in adult stimulant abusers compared
      with placebo. Adult substance abusers were enrolled in this phase I, randomized,
      single-centre, double-blind study. An initial cohort of three subjects was
      enrolled to assess safety followed by a primary cohort that consisted of nine
      subjects. Single i.v. doses of LDX (25 or 50 mg), immediate-release d-amphetamine
      sulphate (10 or 20 mg) or placebo were administered at a minimum of 48-h
      intervals in a single-dose, three-way crossover design. 20 mg of d-amphetamine
      showed significantly increased abuse-related liking scores compared with placebo
      (P < 0.05), whereas the liking effects of 50 mg LDX did not significantly differ
      from placebo. The mean C(max) of d-amphetamine was 38.9 +/- 8.1 and 105 +/- 91.4
      ng/ml after the administration of 50 mg LDX and 20 mg d-amphetamine respectively.
      The mean T(max) of d-amphetamine was 2.51 h after the administration of 50 mg LDX
      and 0.82 h after the administration of 20 mg d-amphetamine. LDX was well
      tolerated in this population. In contrast to d-amphetamine, LDX administered
      intravenously did not produce significant subjective abuse-related liking scores
      at assessed doses.

PMID- 18635708
TI  - Isolation rearing impairs novel object recognition and attentional set shifting
      performance in female rats.
AB  - It has been suggested that the isolation rearing paradigm models certain aspects
      of schizophrenia symptomatology. This study aimed to investigate whether
      isolation rearing impairs rats' performance in two models of cognition: the novel
      object recognition (NOR) and attentional set-shifting tasks, tests of episodic
      memory and executive function, respectively. Two cohorts of female Hooded-Lister
      rats were used in these experiments. Animals were housed in social isolation or
      in groups of five from weaning, post-natal day 28. The first cohort was tested in
      the NOR test with inter-trial intervals (ITIs) of 1 min up to 6 h. The second
      cohort was trained and tested in the attentional set-shifting task. In the NOR
      test, isolates were only able to discriminate between the novel and familiar
      objects up to 1-h ITI, whereas socially reared animals remembered the familiar
      object up to a 4-h ITI. In the attentional set-shifting task, isolates were
      significantly and selectively impaired in the extra-dimensional shift phase of
      the task (P < 0.01). Rats reared in isolation show impaired episodic memory in
      the NOR task and reduced ability to shift attention between stimulus dimensions
      in the attentional set-shifting task. Because schizophrenic patients show similar
      deficits in performance in these cognitive domains, these data further support
      isolation rearing as a putative preclinical model of the cognitive deficits
      associated with schizophrenia.

PMID- 18635709
TI  - Reduced memory and attention performance in a population-based sample of young
      adults with a moderate lifetime use of cannabis, ecstasy and alcohol.
AB  - Regular use of illegal drugs is suspected to cause cognitive impairments. Two
      substances have received heightened attention: 3,4-methylenedioxymethamphetamine
      (MDMA or 'ecstasy') and delta-9-tetrahydrocannabinol (THC or 'cannabis').
      Preclinical evidence, as well as human studies examining regular ecstasy
      consumers, indicated that ecstasy use may have negative effects on learning,
      verbal memory and complex attentional functions. Cannabis has also been linked to
      symptoms of inattention and deficits in learning and memory. Most of the
      published studies in this field of research recruited participants by means of
      newspaper advertisements or by using word-of-mouth strategies. Because
      participants were usually aware that their drug use was critical to the research
      design, this awareness may have caused selection bias or created expectation
      effects. Focussing on attention and memory, this study aimed to assess cognitive
      functioning in a community-based representative sample that was derived from a
      large-scale epidemiological study. Available data concerning drug use history
      allowed sampling of subjects with varying degrees of lifetime drug experiences.
      Cognitive functioning was examined in 284 young participants, between 22 and 34
      years. In general, their lifetime drug experience was moderate. Participants
      completed a neuropsychological test battery, including measures for verbal
      learning, memory and various attentional functions. Linear regression analysis
      was performed to investigate the relationship between cognitive functioning and
      lifetime experience of drug use. Ecstasy and cannabis use were significantly
      related to poorer episodic memory function in a dose-related manner. For
      attentional measures, decrements of small effect sizes were found. Error measures
      in tonic and phasic alertness tasks, selective attention task and vigilance
      showed small but significant effects, suggesting a stronger tendency to
      experience lapses of attention. No indication for differences in reaction time
      was found. The results are consistent with decrements of memory and attentional
      performance described in previous studies. These effects are relatively small;
      however, it must be kept in mind that this study focussed on assessing young
      adults with moderate drug use from a population-based study.

PMID- 18635710
TI  - The potential relationship between QTc interval prolongation and ziprasidone
      treatment: three cases.
AB  - QTc interval prolongation may appear as a consequence of both typical and
      atypical antipsychotic treatments. Ziprasidone, which is effective in treating
      schizophrenia, is associated with QTc prolongation. Although the prolongation of
      QTc with ziprasidone treatment is often pronounced, there is a scarce number of
      cases reported about the relationship between ziprasidone and QTc prolongation.
      Of the three cases presented in this case series, two cases showed values
      exceeding 0.50 s with ziprasidone treatment.

PMID- 18635711
TI  - The effects of opioid receptor blockade on experimental panic provocation with
      CO2.
AB  - Several reports have linked, among other aspects, the role of an opioid system in
      respiratory physiology with underlying mechanisms of panic attacks. The
      involvement of the opioid system in experimental panic is to be further probed.
      This study aimed to determine whether opioid blockade would increase panic
      related symptomatology on provocation with 35% CO2 inhaled by healthy volunteers.
      Participants in a double-blind, randomised crossover design orally received
      either 50 mg of naltrexone or placebo. Most subjects undertook a double
      inhalation of 35% CO2 one hour after pre-medication, and a separate group did so
      after five hours. The reactivity to CO2 and the symptoms elicited by naltrexone
      alone were measured. Among other findings, naltrexone pre-medication alone
      elicited significant increments in panic-related symptoms. Responses to CO2 were
      not significantly different between conditions in either group. These preliminary
      findings suggest that exposure to opioid blockade alone can potentially elicit
      symptoms that resemble panic, however, without modifying the response to
      experimental panic provocation with 35% CO2.

PMID- 18635712
TI  - Positive interference of the analgesic nefopam in the urine immunoassay for
      benzodiazepines in a secure setting.
AB  - An inpatient on a secure unit with a history of bipolar affective disorder and
      physical complaints including pain was prescribed carbamazepine, quetiapine,
      dihydrocodeine, nefopam, paracetamol and various aperients. A benzodiazepine
      urine test by immunoassay was positive. Initial literature searches did not
      suggest a candidate drug for positive interference. Other explanations were
      excluded. Positive results continued, despite room searches and other disruptive
      security measures. Further literature searches revealed one experimental series
      demonstrating positive interference of nefopam in the relevant assay.
      Benzodiazepine assays were negative after cessation of nefopam. This is the first
      such clinical case to our knowledge.

PMID- 18635713
TI  - Outcomes for schizophrenia patients with clozapine treatment: how good does it
      get?
AB  - The objective of this study was to describe the extent/change (2000-2004) of
      clozapine prescribing in schizophrenia in New Zealand and examine the outcomes
      associated with increasing treatment duration, and vs. those who discontinue
      clozapine. Consecutive chart reviews were conducted for adult outpatients in
      Auckland/Northland regions (T1 = 31 March 2000, T2 = 31 October 2001, T3 = 31
      March 2003, T4 = 31 October 2004). Data collected included: patient
      characteristics, social/functional indicators, diagnosis, duration of illness,
      psychiatric admissions and treatment information (psychotropic medication, dose,
      route of administration). Between 2000 and 2004, clozapine for schizophrenia
      increased from 21.0% to 32.8%. Of those prescribed clozapine at T1, 86.1% were
      engaged with community services at T4 and 93.2% still prescribed clozapine.
      Continuing clozapine treatment (vs. other treatment) led to a trend to higher
      rates of regular occupational activity (37% vs. 14.3%) and lower rates of
      compulsory treatment (25.1% vs. 46.4%) and significantly lower hospitalisation
      rates (mean = 0.6 vs. mean = 3.1). For those prescribed clozapine at T4,
      increasing treatment duration (< or = 10 months, 2-3 years, >3 years) led to a
      trend to higher rates of living independently (18% vs. 29.2% vs. 34%) and regular
      occupational activity (26.2% vs. 32.6% vs. 37.5%), and significantly reduced
      compulsory treatment (44.3% vs. 36.9% vs. 28.6%) and hospitalisation rates in the
      previous 18 months (1.5 vs. 0.5 vs. 0.2). Clozapine use increased significantly
      over 4.5 years to expected rates of treatment-resistant schizophrenia. Low
      clozapine discontinuation rates were found and continuing treatment was
      associated with real-world improvements in functional and clinical outcomes.
      These findings support the recommendation of prolonged clozapine trials to
      improve cost-effectiveness in the most seriously unwell schizophrenia patients.

PMID- 18635714
TI  - Wine and drug evaluations: lessons on making comparisons of noninferiority.

PMID- 18635715
TI  - The broad clinical spectrum of bipolar disorder: implications for research and
      practice.

PMID- 18635716
TI  - The broad spectrum of bipolar disorder: implications for research and practice --
      a commentary.

PMID- 18635717
TI  - On being bipolar without being bipolar.

PMID- 18635718
TI  - Commentary on the paper of Smith, et al.

PMID- 18635719
TI  - Overcoming the current approach in bipolar disorder research: towards DSM-V and
      beyond.

PMID- 18635721
TI  - Establishing non-inferiority in treatment trials in psychiatry: guidelines from
      an Expert Consensus Meeting.
AB  - Comparing the efficacy of different treatments in psychiatry is difficult for
      many reasons, even when they are investigated in "head-to-head" studies. A
      consensus meeting was, therefore, held to produce best practice guidelines for
      such studies. This article presents the conclusions of this consensus and
      illustrates it using published data in the field of antidepressant treatment of
      generalized anxiety disorder.

PMID- 18635722
TI  - A non-inferiority comparison of duloxetine and venlafaxine in the treatment of
      adult patients with generalized anxiety disorder.
AB  - The present study is a non-inferiority comparison of duloxetine 60-120 mg/day and
      venlafaxine extended-release (XR) 75-225 mg/day for the treatment of adults with
      generalized anxiety disorder (GAD). The non-inferiority test was a prespecified
      plan to pool data from two nearly identical 10-week, multicentre, randomized,
      placebo-controlled, double-blind studies of duloxetine 60-120 mg/day and
      venlafaxine 75-225 mg/ day for the treatment of GAD. An independent expert
      consensus panel provided six statistical and clinical criteria for determining
      non-inferiority between treatments. Response was defined as > or =50% reduction
      in Hamilton Anxiety Rating Scale (HAMA) total score. In the pooled sample,
      patients were randomly assigned to duloxetine (n = 320), venlafaxine XR (n = 333)
      or placebo (n = 331). For the non-inferiority analysis, the per-protocol patients
      who were treated with duloxetine (n = 239) or venlafaxine XR (n = 262) improved
      significantly more (mean HAMA reductions were -15.4 and -15.2, respectively) than
      placebo-treated patients (n = 267; -11.6, P < or = 0.001, both comparisons).
      Response rates were 56%, 58% and 40%, respectively. Discontinuation rate because
      of AEs was significantly higher for duloxetine (13.4%, P < or = 0.001) and
      venlafaxine XR (11.4%, P < or = 0.01) groups compared with placebo (5.4%).
      Duloxetine 60-120 mg/day met all statistical and clinical criteria for non
      inferiority and exhibited a similar tolerability profile compared with
      venlafaxine XR 75-225 mg/day for the treatment of adults with GAD.

PMID- 18635723
TI  - Adequacy of venlafaxine dose prescribing in major depression and hospital
      resources implications.
AB  - Venlafaxine, a dual serotonin and noradrenaline re-uptake inhibitor, has been
      found to be effective at doses below 375 mg daily, but for patients with major
      depression higher doses can be required. In this retrospective naturalistic
      study, we investigated the effectiveness and resource implications of prescribing
      higher than standard doses of venlafaxine (tablet preparation). Ninety-six
      outpatients fulfilling DSM-IV criteria for major depressive disorder were
      assigned to two demographically matched cohorts: cohort A, receiving high doses
      (n = 38; doses > or =375 mg/day) and cohort B, receiving standard doses (n = 58;
      doses <375 mg/day). Data on hospital resources, drugs and medical profiles were
      extracted from patients' records. Information on cohort A was also obtained
      before their high-dose regime, while taking standard doses. A within-group
      analysis of cohort A showed that patients spent fewer days in hospital (P = 0.03)
      and had fewer outpatients visits (P < 0.01) when on high doses than when on
      standard doses. A between-group analysis found that cohort A, while on higher
      doses, had fewer outpatient visits compared with cohort B (P < 0.01). Patients in
      both groups had satisfactory drug tolerability and efficacy profiles. There were
      no differences between cohorts with regard to baseline characteristics, a part
      from the more intensive use of additional medications made by cohort A. Our
      preliminary investigation suggests that higher doses of venlafaxine may be cost
      saving in relation to selected hospital resources. However, one cannot firmly
      conclude that the change in service use is due to the higher-dose regime, and we
      recommend further research to ascertain the cost-effectiveness of adequate dose
      prescribing in patients with poor symptom resolution at lower doses of
      venlafaxine.

PMID- 18635724
TI  - A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9-
      tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures
      in regular users of marijuana.
AB  - Heavy use of marijuana is claimed to damage critical skills related to short-term
      memory, visual scanning and attention. Motor skills and driving safety may be
      compromised by the acute effects of marijuana. The aim of this study was to
      investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol
      (THC) on skills important for coordinated movement and driving and on subjective
      and autonomic measures in regular users of marijuana. Fourteen regular users of
      marijuana were enrolled. Each subject was tested on two separate days. On each
      test day, subjects smoked two low-nicotine cigarettes, one with and the other
      without THC. Seventeen mg THC was included in the cigarette on one test day and
      13 mg on the other day. The sequence of cigarette types was unknown to the
      subject. During smoking, heart rate and blood pressure were monitored, and the
      subjects performed a virtual reality maze task requiring attention and motor
      coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test
      (WCST), a "gambling" task and estimation of time and distance from an approaching
      car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the
      walls more often on the virtual maze task than after smoking cigarettes without
      THC; this effect was not seen in patients after they smoked cigarettes with 13 mg
      THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent
      with the use of 13 mg THC. Decision making in the gambling task was affected
      after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking
      cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and
      satisfaction, drug "effect" and drug "high". These findings imply that smoking of
      17 mg THC results in impairment of cognitive-motor skills that could be important
      for coordinated movement and driving, whereas the lower dose of 13 mg THC appears
      to cause less impairment of such skills in regular users of marijuana.

PMID- 18635725
TI  - Bouncing back: is the bipolar rebound phenomenon peculiar to lithium? A
      retrospective naturalistic study.
AB  - In bipolar disorder the discontinuation of lithium prophylaxis is associated with
      early episode precipitation. Is this ;rebound' phenomenon peculiar to lithium?
      This naturalistic retrospective case note review investigated the frequency of
      immediate recurrence after discontinuation of any prophylactic treatment. Bipolar
      patients who stopped at least one medication after at least 6 months of remission
      were studied. A total of 310 case notes were examined in a systematic search. A
      total of 53 cases of discontinuation in 48 subjects were found. Discontinued
      medications included lithium, valproate, carbamazepine, typical and atypical
      antipsychotics and antidepressants. Recurrence occurred within 3 months of
      medication withdrawal in 39 cases (74%). Over half of the discontinuation
      episodes involved lithium: recurrence occurred in 86% of these cases. In the
      groups stopping other prophylactic agents, a majority of subjects suffered
      recurrence: anticonvulsants (89%), antipsychotics (64%) and antidepressants
      (58%). However, these groups were small and the clarity of the data was
      undermined by the simultaneous withdrawal of other agents. Manic and hypomanic
      episodes were the most common form of recurrences. Depressive episodes occurred
      proportionately most frequently following antidepressant withdrawal. More than
      half of recurrences required hospital admission. This study provides preliminary
      naturalistic evidence that early episode recurrence in bipolar disorder is not
      peculiar to lithium withdrawal but may occur following withdrawal of medication
      from all classes recommended in prophylaxis. These findings, if replicated, have
      important implications for clinical practice and for research.

PMID- 18635726
TI  - Reply to letter by Green, Marsden and Fone (2007) about Sessa and Nutt's
      editorial (MDMA: baby with the bath water) in the November 2007 journal.

PMID- 18635727
TI  - Global public health and gender theory: the need for integration.

PMID- 18635728
TI  - Young people's use of sports facilities: a Norwegian study on physical activity.
AB  - In recent years, sports facilities have formed part of Norwegian public health
      policies to increase physical activity among children and adolescents. Despite
      large sums of public money being spent on such facilities, information on usage
      is limited. AIMS: Our aim was to study the effects of gender, age and relative
      activity level on young people's use of sports facilities. METHODS: We explored
      662 young people's (age 6-16 years) usage of 19 different kinds of sports
      facilities. A questionnaire was administered to students and teachers, and
      situation plots of students at recess were made. RESULTS: The findings indicate
      that sports facilities in general were less used by girls, adolescents (14-16
      years) and the least active (physically active < or = 1 times/week outside
      school) than by boys, children (6-13 years) and the most active (physically
      active > or = 4 times/ week outside school). More general, multifunctional
      facilities were used to a greater extent than specialized facilities,
      particularly by the least active. Distance to facility was important for the use
      of common facilities. CONCLUSIONS: These results raise the question of whether
      sports facilities significantly increase physical activity among "all'' young
      people, which is the government's stated goal. More research on sports facilities
      use and physical activity levels among males and females of all ages is
      warranted.

PMID- 18635729
TI  - The potential migration effect of rural hospital closures: a Danish case study.
AB  - AIMS: Rural hospital closures are high on the current healthcare agenda in
      Denmark. One concern raised is that rural hospital closures may further decrease
      population numbers in rural areas, as closures may induce some residents to move
      away from affected areas, i.e. closer to healthcare services elsewhere. The aim
      of this study was to investigate whether rural hospital closures may lead to out
      migration in a Danish setting and to investigate which socioeconomic groups would
      be most likely to migrate. METHODS: The island of AEro was selected as the case
      study area. The island has one small hospital. By the use of fully structured
      telephone interviews, a representative sample of AEro inhabitants (N=1000) was
      asked how important it was for them to live close to a hospital and whether they
      would consider moving away if their hospital was closed. RESULTS: Forty-seven per
      cent found it very important to live close to a hospital, and 29% would consider
      moving away if their hospital was closed. Multiple regression analyses showed
      that families with children were most likely to consider moving away and elderly
      people were least likely to consider moving away. CONCLUSIONS: The study suggests
      that rural hospital closures may lead to out-migration, although the hypothetical
      method of questioning leaves uncertainty about the actual scale of out-migration.
      Families with children appear to be the most likely out-migrants. Elderly people
      may be hardest hit by a hospital closure, being most reliant on healthcare and
      least inclined to move away.

PMID- 18635730
TI  - Job stress, sickness absence and sickness presenteeism in Nordic elderly care.
AB  - AIMS: Nordic elderly care has been restructured to obtain more efficiency. Among
      workers caring for the elderly, levels of perceived job stress could vary, due to
      understaffing and resource scarcity. This study examines how sickness absence and
      sickness presenteeism are associated with perceived job stress. METHODS: Data
      were obtained by posting questionnaires to lower-level care staff in Sweden
      (n=483), Denmark (n=704), Finland (n=597), and Norway (n=663). Self-reports about
      job stress (four items), sickness absence and sickness presenteeism were analysed
      by cross-tabulations and logistic regression. RESULTS: Each item of job stress
      was associated with sickness absence and sickness presenteeism in the samples
      from all four countries. With low levels of job stress, levels of reported
      sickness absence and sickness presenteeism were relatively moderate. With
      increasing levels of job stress, the level of sickness presenteeism rose more
      sharply than that of sickness absence. CONCLUSIONS: The results can be
      interpreted in the light of features inherent in care work. Owing to professional
      norms and moral obligations, care workers could lower their thresholds for taking
      sick leave when care organizations are understaffed, because absences will be
      particularly critical for care recipients in such circumstances. Thus, while
      increasing job stress tends to be accompanied both by more sickness absence and
      by more sickness presenteeism, sickness presenteeism rises particularly in cases
      of high levels of job stress. Owing to cross-sectional data and self-reported
      information, conclusions are tentative.

PMID- 18635731
TI  - Regional variations and determinants of direct psychiatric costs in Sweden.
AB  - AIM: The aim of the present study was to investigate socioeconomic and
      demographic determinants of direct costs for psychiatric disorders in Sweden. The
      cost categories were inpatient and outpatient costs, and costs for
      psychopharmacological drugs. Two consecutive years, 2001 and 2002, were chosen as
      the study period. METHODS: The study included all costs for admissions, visits
      and prescribed drugs for adults aged > or = 18 years in 2001 and 2002 in Sweden.
      These costs were aggregated and analysed at the county level. A multiple linear
      regression analysis was fitted to the data, and independent variables (i.e.
      predictors) were chosen on the basis of previous studies. All cost types (e.g.
      total, inpatient, outpatient and drug costs) were analysed separately in
      different models. RESULTS: Large variations in total direct psychiatric costs
      were found between county councils (for example, the total costs varied between
      euro112 and euro195 per capita in 2001). The results indicate that psychiatric
      outpatient care is less utilized in rural than in urban areas, and drugs are more
      often prescribed in rural areas than in urban areas. Areas with a high proportion
      of women and people aged 65 years and over are strong predictors of mental
      healthcare costs, i.e. variables showing that the higher the proportion, the
      lower the direct costs. CONCLUSIONS: Factors such as urbanization, gender, age
      and number of immigrants are reasons for differences in psychiatric direct costs.
      On the basis of these findings, it seems plausible to conclude that women, older
      patients and immigrants may benefit from specialized psychiatry, but that such
      healthcare does not seem to be provided in all regions.

PMID- 18635732
TI  - Regional differences in alcohol consumption, alcohol addiction and drug use among
      Swedish adults.
AB  - INTRODUCTION: Alcohol consumption and drug use, as well as alcohol- and drug
      related problems, vary considerably in different regions in Sweden, and between
      men and women of different ages. AIM: The aim of the present study was to examine
      the regional, gender and socioeconomic distribution of risk consumption of
      alcohol, alcohol dependency and drug use in a random sample in Sweden. MATERIAL
      AND METHODS: In both May 2003 and 2004, 7200 gender-stratified adults (a total of
      14,400), randomly selected from 12 regions in Sweden, were contacted by mail, and
      asked to fill out an enclosed questionnaire. The questionnaire concerned use of
      alcohol, alcohol-related problems, and use of illicit drugs. RESULTS: Heavy
      alcohol consumption and cannabis use were more frequent in the south of Sweden
      than in the north, and the further north, the lower the frequency. Alcohol and
      drug use decreased with age, and was higher for men than for women. On average,
      11.5% of all men and 5.0% of all women consumed alcohol intensively at least
      weekly, 8.6% of men and 4.5% of women had a generally high alcohol consumption,
      4.1% of men and 2.5% of women were alcohol addicted, and 2.9% of men and 1.3% of
      women had used cannabis during the last 12 months. CONCLUSIONS: High alcohol
      consumption and use of illegal drugs seem to be more prevalent in those parts of
      Sweden that are closer to the European continent. In our opinion, this might be
      an effect of the closeness to other European countries with lower prices for
      alcohol, less strict alcohol control policies, and higher availability of drugs.
      Consideration of regional, gender and age differences in problems related to
      alcohol and drugs seem to be important in the planning and development of
      preventive activities.

PMID- 18635733
TI  - Effects of residential changes and time patterns on external-cause mortality in
      migrants: results of a German cohort study.
AB  - AIMS: Immigrants are at increased risk of dying from external causes,
      particularly suicide. This study presents mortality data from a complete follow
      up of a cohort of immigrants from the Former Soviet Union to Germany. Number of
      residential changes after migration and time period between residential change
      and death are analysed as predictors for suicide and other causes of mortality.
      METHODS: A representative cohort of immigrants (n=34,393) was followed up until
      31 December 2002. Residential changes were monitored through city registries.
      Standardized mortality ratios were calculated for all causes of death and
      external causes of death (suicides, accidents, other external causes) and deaths
      attributable to psychoactive substance use. Data on residential change were
      analysed using Poisson regression to examine differences in external-cause
      mortality among immigrants who changed residence after immigration. Mortality
      rates by time since changing residence were calculated, and linear regression
      analysis was performed to model the effect of cause of death on the time interval
      between residential change and death. RESULTS: Male immigrants had a
      significantly higher risk of dying from external causes and suicide than Germans,
      and this increases with frequency of residential changes. Suicide mortality was
      significantly higher shortly after residential change. Linear regression showed
      that time to death after residential change was 2.5 times shorter for suicide
      than for any other cause. CONCLUSIONS: High risk of death from external causes
      and from deaths attributable to substance abuse in immigrants suggests
      integration problems. Preventive efforts at targeted integration programmes for
      immigrants, in particular shortly after residential change, are recommended.

PMID- 18635734
TI  - Enhancing concentration, mood and memory in healthy individuals: an empirical
      study of attitudes among general practitioners and the general population.
AB  - AIM: To study attitudes towards enhancing concentration, mood and memory in
      healthy individuals among the general public and general practitioners (GPs).
      METHODS: A questionnaire consisting of vignettes including three cases dealing
      with enhancement of concentration, mood and memory was sent during 2006 to 1000
      randomly selected people from Stockholm and 300 GPs. We asked about the use of
      pharmaceuticals for healthy individuals for the benefit of others and the benefit
      to oneself; we also asked whether or not society should pay the cost. Finally, we
      asked about enhancement of healthy people's concentration, mood and memory
      through the use of natural remedies. RESULTS: Fifty-two per cent of the general
      public and 39% of the GPs responded. While the use of natural remedies was
      perceived as fairly acceptable, majorities in both groups were negative with
      regard to the use of pharmaceuticals to enhance concentration, mood and memory in
      a healthy individual. The general public tended to be less negative than the GPs.
      There was a significant difference between the reasons for providing enhancement;
      altruistic reasons seem to be more acceptable than egoistic ones. For both
      groups, enhancing mood was more controversial than enhancing memory. CONCLUSIONS:
      Despite the large dropout rate, the study indicates that enhancement by means of
      natural remedies of different human capacities is acceptable to the general
      public, while only small minorities of both groups are inclined to allow the use
      of pharmaceuticals. When compared to the egoistic reason, the altruistic one for
      enhancing concentration, mood and memory with pharmaceuticals seems to influence
      the general public's inclination to support prescriptions; this was also the case
      among the GPs, but only as regards mood enhancement.

PMID- 18635735
TI  - Anger expression, negative life events and violent behaviour among male college
      students in Ethiopia.
AB  - AIMS: To assess the prevalence of violent behaviour and to identify risk factors
      associated with violent behaviour among male college students in Ethiopia.
      METHODS: A cross-sectional study among 1294 male college students in Awassa,
      Ethiopia was conducted in June 2006. A self-administered questionnaire was used
      to collect information concerning violent acts, anger expression, and
      sociodemographic and lifestyle characteristics. Multivariable logistic regression
      procedures were used to calculate adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs). RESULTS: More than half of the students (54.3%) reported
      committing at least one act of physical violence during the current academic
      year. Academic year of studies, use of khat, a natural stimulant with amphetamine
      like effects, anger proneness and stressful life events were statistically
      significant covariates associated with committing acts of violence. Seniors, as
      compared with freshmen, were less likely to admit violent behaviour (OR=0.46; 95%
      CI 0.30-0.71). Those who reported using khat were more likely to report
      committing violent acts (OR=1.46, 95% CI 1.02-2.08) than were non-users. Students
      with moderate levels of anger expression (scores of 11- 14) were 3.40 times more
      likely to report committing acts of violence (OR=3.40; 95% CI 2.42-4.79) than
      were those with low levels of anger expression (scores v11). For students with
      high levels of anger expression (> or = 15 scores), the corresponding OR was 7.62
      (95% CI 5.15-11.29). Participants who had experienced > or = 4 negative life
      events during the current academic year were more likely (OR=2.41; 95% CI 1.58
      3.69) to report violent behaviour than were those with fewer stressful life
      events. CONCLUSIONS: Screening for violent behaviour and violence prevention
      programmes, particularly those in educational settings, should include strategies
      that address students' stressful life events, anger management, and substance
      use.

PMID- 18635736
TI  - Time trends in incidence of myocardial infarction in male and female dominated
      occupations in Stockholm, Sweden.
AB  - AIMS: To investigate time trends in first acute myocardial infarction (MI)
      incidence in male and female dominated occupations in Stockholm during 1977-1996.
      METHODS: Population-based case-control study, where all first events of acute MI
      among participants aged 40-69 in Stockholm 1977-1996 were identified, using
      registers of hospital discharges and deaths. Controls were selected randomly
      using national population registers. There were 16,531 male and 4382 female cases
      and 117,015 male and 102,083 female controls. In all, 222 female cases worked in
      male dominated occupations and 844 male cases worked in female dominated
      occupations. RESULTS: Both women and men in male dominated occupations showed an
      elevated relative risk of first MI compared to other employees during the study
      period. Between 1985-1996, when there was a general decline in MI incidence in
      Sweden, women in male dominated occupations tended to show an increasing trend.
      Women in female dominated high and intermediate occupations had a lower relative
      risk of MI compared to other women in the same socioeconomic group. In male
      dominated and non-manual female dominated occupations a decline in the incidence
      of MI was seen during 1985-1996 in men but not in women. CONCLUSIONS: Work in
      male dominated occupations appears to be associated with an increased risk of MI
      in both genders. There is a need to investigate possible work related or other
      factors that may be driving this elevated risk.

PMID- 18635737
TI  - A new public health policy in Sweden.

PMID- 18635738
TI  - Production of multivalent protein binders using a self-trimerizing collagen-like
      peptide scaffold.
AB  - A class of multivalent protein binders was designed to overcome the limitations
      of low-affinity therapeutic antibodies. These binders, termed "collabodies," use
      a triplex-forming collagen-like peptide to drive the trimerization of a
      heterologous target-binding domain. Different forms of collabody, consisting of
      the human single-chain variable fragment (scFv) fused to either the N or C
      terminus of the collagen-like peptide scaffold (Gly-Pro-Pro)(10), were stably
      expressed as soluble secretory proteins in mammalian cells. The collabody
      consisting of scFv fused to the N terminus of collagen scaffold is present as a
      homotrimer, whereas it exhibited a mixture of trimer and interchain disulfide
      bonded hexamer when cysteine residues were introduced and flanked the scaffold.
      The collagenous motif in collabody is prolyl-hydroxylated, with remarkable
      thermal and serum stabilities. The collabody erb_scFv-Col bound to the
      extracellular domain of epidermal growth factor receptor with a binding strength
      approximately 20- and 1000-fold stronger than the bivalent and monovalent
      counterparts, respectively. The trimeric collagen scaffold does not compromise
      the functionality of the binding moieties of parental immunoglobulin G (IgG);
      therefore, it could be applied to fuse other protein molecules to acquire
      significantly improved targeting-binding strengths.

PMID- 18635739
TI  - T-cadherin modulates hepatocyte functions in vitro.
AB  - Primary hepatocytes from several different species rapidly lose viability and
      phenotypic functions on isolation from their native microenvironment of the
      liver. Stromal cells derived from both within and outside the liver can induce
      phenotypic functions in primary hepatocytes in vitro; however, the molecular
      mediators underlying this "coculture effect" have not been fully elucidated. We
      have previously developed a functional genomic screen utilizing cocultures of
      hepatocytes and 3T3 fibroblasts to identify such candidate hepatocyte-function
      inducing molecules. In particular, truncated-cadherin (T-cadherin) was identified
      as a potential molecule of interest in induction of hepatic functions. Here we
      demonstrate that liver-specific functions of primary rat hepatocytes are induced
      on cocultivation with Chinese hamster ovary cells engineered to express T
      cadherin on their surface as compared with wild-type controls. Additionally,
      culture of cells on substrata presenting recombinant T-cadherin protein
      (acellular presentation) enhanced hepatic functions in both pure hepatocyte
      cultures and in hepatocyte-stromal cocultures lacking endogenous T-cadherin
      expression. Collectively, these data indicate that both cellular and acellular
      presentation of T-cadherin can be used to modulate the hepatocyte phenotype in
      vitro for tissue engineering applications. Our work suggests potential avenues
      for investigating the role of T-cadherin on hepatocellular function in vivo in
      settings such as embryogenesis and liver pathology.

PMID- 18635740
TI  - Characterising cortical density in the mid-tibia: intra-individual variation in
      adolescent girls and boys.
AB  - BACKGROUND: Inter-individual differences in cortical bone volumetric density
      (CoD), such as those related to sex, are a product of differences in remodelling
      rates. While cortical bone is often treated as a uniform tissue, remodelling
      rates also vary within individual bones. This level of adaptation has largely
      been overlooked in analyses of peripheral quantitative computed tomography (pQCT)
      images. Further, such variation in CoD has never been assessed in growing bones.
      We hypothesised that CoD varied significantly within the same cross-section of
      the mid-tibia of adolescents. We further hypothesised that due to the profound
      impact of oestrogen on remodelling, this variation would be different between
      sexes. METHODS: Subjects were 183 adolescents (99 girls and 84 boys) in grade 6
      and 7 with a mean age of 12.1 years. We used age at peak height velocity to
      adjust for maturational differences between sexes. Image data from a mid-tibia
      pQCT scan of each subject were assessed regionally within eight sectors
      distributed about the cortex and aligned by the anterior tibial crest. We used a
      repeated measures general linear model to assess intra-individual variation in
      CoD while controlling for differences in ethnicity, maturity, height, weight,
      physical activity level and total cross-sectional bone area (ToA). RESULTS:
      Sector based variation in CoD was significant (p<0.001), with the anterior cortex
      having lower density than the posterior cortex. The largest percentage difference
      (anterior vs posteromedial sectors) was 12.2%. A significant sector*sex
      interaction (p = 0.018) was detected; however, its impact was relatively small
      with girls having 1.1-3.6% denser bones than boys depending on the sector (2.7%
      average difference). CONCLUSIONS: The magnitude of the variation in CoD across
      sectors within individuals of both sex was far greater than the mean differences
      between the sexes. This finding indicates that the microstructural variation
      within the mid-tibia is detectable by pQCT and its magnitude suggests an
      important level of adaptation to loading.

PMID- 18635741
TI  - Is low self-control associated with violence among youths in Turkey?
AB  - Self-control theory is tested in relation to violence on a sample of university
      students in Turkey. The primary findings indicate support for the theory net of
      the impacts of strain, deterrence, differential association, social bonding, and
      routine activity theories: The greater the low self-control, the greater the
      violence. No subdimensions of self-control have consistent significant impacts on
      violence. Most high-opportunity measures have positive impacts on violence.
      Interaction effects occur only among subdimensions of self-control and
      opportunity variables. Social class and age are significant even when low self
      control measures were controlled.

PMID- 18635742
TI  - Deviations in populations of peripheral blood mononuclear cells and endometrial
      macrophages in the cow during pregnancy.
AB  - The presence of conceptus alloantigens necessitates changes in maternal immune
      function. Here, we used the cow to evaluate whether species with epitheliochorial
      placentation have changes in specific leukocyte populations during pregnancy
      similar to those reported in species with hemotropic placentae. At days 33-34 of
      pregnancy, there was no effect of pregnancy status on the number of cells
      positive for CD8, CD4, gammadeltaT cell receptor, or the monocyte marker CD68 in
      the peripheral blood mononuclear cell (PBMC) population. There was, however, an
      increase in the proportion of CD4(+) cells that were positive for CD25. There was
      no effect of status on the proportion of PBMCs that were CD8(+) when comparing
      preparturient cows to nonpregnant cows. However, preparturient cows had an
      increased percentage of PBMCs that were gammadeltaT cells and CD4(+)CD25(+) and a
      tendency for a lower percentage that were CD68(+) cells. Using immunolocalization
      with anti-CD68, it was found that pregnant cows had increased numbers of CD68(+)
      cells in the endometrial stroma as early as days 54-100 of gestation; this
      increase persisted through the last time examined (day 240 of gestation). Cells
      positive for CD68 were also positive for another macrophage/monocyte marker,
      CD14. In conclusion, pregnancy in the cow is associated with changes in
      peripheral and endometrial leukocyte numbers, which are similar to patterns
      observed in other species.

PMID- 18635743
TI  - Role of transforming growth factor-beta1 in gene expression and activity of
      estradiol and progesterone-generating enzymes in FSH-stimulated bovine granulosa
      cells.
AB  - Survival and inhibitory factors regulate steroidogenesis and determine the fate
      of developing follicles. The objective of this study was to determine the role of
      transforming growth factor-beta1 (TGFB1) in the regulation of estradiol-17beta
      (E(2)) and progesterone (P(4)) secretion in FSH-stimulated bovine granulosa
      cells. Granulosa cells were obtained from 2 to 5 mm follicles and cultured in
      serum-free medium. FSH dose (1 and 10 ng/ml for 6 days) and time in culture (2,
      4, and 6 days with 1 ng/ml FSH) increased E(2) secretion and mRNA expression of
      E(2)-related enzymes cytochrome P450 aromatase (CYP19A1) and 17beta
      hydroxysteroid dehydrogenase type 1 (HSD17B1), but not HSD17B7. TGFB1 in the
      presence of FSH (1 ng/ml) inhibited E(2) secretion, and decreased mRNA expression
      of FSH receptor (FSHR), CYP19A1, and HSD17B1, but not HSD17B7. FSH dose did not
      affect P(4) secretion and mRNA expression of 3beta-hydroxysteroid dehydrogenase
      (HSD3B) and alpha-glutathione S-transferase (GSTA), but inhibited the amount of
      steroidogenic acute regulatory protein (STAR) mRNA. Conversely, P(4) and mRNA
      expression of STAR, cytochrome P450 side-chain cleavage (CYP11A1), HSD3B, and
      GSTA increased with time in culture. TGFB1 inhibited P(4) secretion and decreased
      mRNA expression of STAR, CYP11A1, HSD3B, and GSTA. TGFB1 modified the formation
      of granulosa cell clumps and reduced total cell protein. Finally, TGFB1 decreased
      conversion of androgens to E(2), but did not decrease the conversion of estrone
      (E(1)) to E(2) and pregnenolone to P(4). Overall, these results indicate that
      TGFB1 counteracts stimulation of E(2) and P(4) synthesis in granulosa cells by
      inhibiting key enzymes involved in the conversion of androgens to E(2) and
      cholesterol to P(4) without shutting down HSD17B reducing activity and HSD3B
      activity.

PMID- 18635744
TI  - Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer.
AB  - BACKGROUND AND AIMS: Chromosomal instability (CIN) is recognised as a hallmark of
      cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis
      segregation during mitosis. Although the recent identification of human shugoshin
      (hSgo1), an important player in proper chromosome segregation, has suggested the
      involvement of hSgo1 in colorectal tumourigenesis, little is known about how it
      is involved. The aim of this study was to obtain information about the status of
      hSgo1 in human colorectal cancer. METHOD AND RESULTS: Among the 46 colorectal
      cancer cases, hSgo1 mRNA expression was decreased in the tumour tissue in
      comparison with the corresponding normal tissue (p = 0.032). Human Sgo1
      downregulated tumours (tumour to normal mucosa ratio<0.5) had preferential
      location on the left side large bowel rather than on the right side (p = 0.012),
      and a higher variation of centromere numbers revealed by fluorescence in situ
      hybridisation (FISH). To assess the effects of hSgo1 downregulation, hSgo1
      knockdown was performed by transfecting the diploid HCT116 cell line with a short
      hairpin RNA expression vector. hSgo1 knockdown cells proliferated slowly because
      of both G(2)/M arrest and apoptosis (p<0.001), and markers of CIN in the form of
      aneuploidy (p<0.001) and micronuclei (p<0.005) were later observed in hSgo1
      knockdown cells. Increased centrosome amplification (p<0.05), the presence of
      binucleated cells and mitotic catastrophes were also noted in hSgo1 knockdown
      cells. CONCLUSIONS: These findings suggest that hSgo1-downregulated colorectal
      cancers have a clinicopathological character of CIN, and hSgo1 downregulation
      leads to CIN in colorectal cancer cells.

PMID- 18635745
TI  - The development of drug metabolism research as expressed in the publications of
      ASPET: Part 3, 1984-2008.
AB  - The dramatic changes in drug metabolism research in the last 25 years are well
      documented in the publications of the American Society for Pharmacology and
      Experimental Therapeutics (ASPET). New analytical tools combined with modern
      molecular biological techniques have provided unprecedented access to the
      workings of the cell. A field that concentrated on only a handful of primary
      enzymes now has a list of hundreds in its purview. Genetic variation,
      environmental impact, and molecular diversity have all come under study in
      attempts to follow the fate of drugs and chemicals. Examples from ASPET journals
      will be used to illustrate the dramatic advancements in the field.

PMID- 18635746
TI  - Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver.
AB  - A first step in the enzymatic disposition of the antineoplastic drug doxorubicin
      (DOX) is the reduction to doxorubicinol (DOX-OL). Because DOX-OL is less
      antineoplastic but more cardiotoxic than the parent compound, the individual rate
      of this reaction may affect the antitumor effect and the risk of DOX-induced
      heart failure. Using purified enzymes and human tissues we determined enzymes
      generating DOX-OL and interindividual differences in their activities. Human
      tissues express at least two DOX-reducing enzymes. High-clearance organs (kidney,
      liver, and the gastrointestinal tract) express an enzyme with an apparent Km of
      approximately 140 microM. Of six enzymes found to reduce DOX, Km values in this
      range are exhibited by carbonyl reductase 1 (CBR1) and aldo-keto reductase (AKR)
      1C3. CBR1 is expressed in these three organs at higher levels than AKR1C3,
      whereas AKR1C3 has higher catalytic efficiency. However, inhibition constants for
      DOX reduction with 4-amino-1-tert-butyl-3-(2-hydroxyphenyl)pyrazolo[3,4
      d]pyrimidine (an inhibitor that can discriminate between CBR1 and AKR1C3) were
      identical for CBR1 and human liver cytosol, but not for AKR1C3. These results
      suggest that CBR1 is a predominant hepatic DOX reductase. In cytosols from 80
      human livers, the expression level of CBR1 and the activity of DOX reduction
      varied >70- and 22-fold, respectively, but showed no association with CBR1 gene
      variants found in these samples. Instead, the interindividual differences in CBR1
      expression and activity may be mediated by environmental factors acting via
      recently identified xenobiotic response elements in the CBR1 promoter. The
      variability in the CBR1 expression may affect outcomes of therapies with DOX, as
      well as with other CBR1 substrates.

PMID- 18635748
TI  - Phenylalanine 169 in the second extracellular loop of the human histamine H4
      receptor is responsible for the difference in agonist binding between human and
      mouse H4 receptors.
AB  - Using the natural variation in histamine H(4) receptor protein sequence, we tried
      to identify amino acids involved in the binding of H(4) receptor agonists. To
      this end, we constructed a variety of chimeric human-mouse H(4) receptor proteins
      to localize the domain responsible for the observed pharmacological differences
      between human and mouse H(4) receptors in the binding of H(4) receptor agonists,
      such as histamine, clozapine, and VUF 8430 [S-(2-guanidylethyl)-isothiourea].
      After identification of a domain between the top of transmembrane domain 4 and
      the top of transmembrane domain 5 as being responsible for the differences in
      agonist affinity between human and mouse H(4)Rs, detailed site-directed
      mutagenesis studies were performed. These studies identified Phe(169) in the
      second extracellular loop as the single amino acid responsible for the
      differences in agonist affinity between the human and mouse H(4)Rs. Phe(169) is
      part of a Phe-Phe motif, which is also present in the recently crystallized
      beta(2)-adrenergic receptor. These results point to an important role of the
      second extracellular loop in the agonist binding to the H(4) receptor and provide
      a molecular explanation for the species difference between human and mouse H(4)
      receptors.

PMID- 18635747
TI  - Enzymatic reduction and glutathione conjugation of benzoquinone ansamycin heat
      shock protein 90 inhibitors: relevance for toxicity and mechanism of action.
AB  - Two-electron reduction of benzoquinone ansamycin (BA) heat shock protein (Hsp) 90
      inhibitors by NAD(P)H:quinone oxidoreductase 1 (NQO1) to hydroquinone ansamycins
      (BAH2s) leads to greater Hsp90 inhibitory activity. BAs can also be metabolized
      by one-electron reductases and can interact with glutathione, reactions that have
      been associated with toxicity. Using a series of BAs, we investigated the
      stability of the BAH2s generated by NQO1, the ability of BAs to be metabolized by
      one-electron reductases, and their conjugation with glutathione. The BAs used
      were geldanamycin (GM), 17-(allylamino)-17-demethoxygeldanamycin (17AAG), 17
      demethoxy-17-[[2-(dimethyl amino)ethyl]amino]-geldanamycin (17DMAG), 17-(amino)
      17-demethoxygeldanamycin (17AG), and 17-demethoxy-17-[[2-(pyrrolidin-1
      yl)ethyl]amino]-geldanamycin (17AEP-GA). The relative stabilities of BAH2s at pH
      7.4 were GM hydroquinone>17AAG hydroquinone>17DMAG hydroquinone>17AG hydroquinone
      and 17AEP-GA hydroquinone. Using human and mouse liver microsomes and either
      NADPH or NADH as cofactors, 17AAG had the lowest rate of one-electron reduction,
      whereas GM had the highest rate. 17DMAG demonstrated the greatest rate of redox
      cycling catalyzed by purified human cytochrome P450 reductase, whereas 17AAG
      again had the slowest rate. GM formed a glutathione adduct most readily followed
      by 17DMAG. The formation of glutathione adducts of 17AAG and 17AG were relatively
      slow in comparison. These data demonstrate that GM, the most hepatotoxic BAs in
      the series had a greater propensity to undergo redox cycling reactions catalyzed
      by hepatic one-electron reductases and markedly greater reactivity with thiols
      when compared with the least hepatotoxic analog 17AAG. Minimizing the propensity
      of BA derivatives to undergo one-electron reduction and glutathione conjugation
      while maximizing their two-electron reduction to stable Hsp90 inhibitory
      hydroquinones may be a useful strategy for optimizing the therapeutic index of
      BAs.

PMID- 18635749
TI  - Pitfalls and prevention strategies for liquid chromatography-tandem mass
      spectrometry in the selected reaction-monitoring mode for drug analysis.
AB  - BACKGROUND: We observed cases of false-positive results with the use of liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS). Different LC
      MS/MS techniques that use the selected reaction-monitoring mode, routinely
      employed for the analysis and quantification of drugs and toxic compounds in
      biological matrices, were involved in the false-positive and potentially false
      positive results obtained. We sought to analyze the causes of and solutions to
      this problem. METHODS: We used a previously reported LC-MS/MS general unknown
      screening method, as well as manual spectral investigation in 1 case, to perform
      verification and identification of interfering compounds. RESULTS: We observed
      that false-positive results involved: a metabolite of zolpidem that might have
      been mistaken for lysergic acid diethylamide, benzoylecgonine mistaken for
      atropine, and clomipramine and 3 phenothiazines that share several common ion
      transitions. CONCLUSIONS: To prevent problems such as those we experienced, we
      recommend the use of stable-isotope internal standards when possible, relative
      retention times, 2 transitions or more per compound when possible, and acceptable
      relative abundance ratios between transitions, with an experience-based tolerance
      of +/-15% for transitions with a relative abundance >10% and with an extension to
      +/-25% for transitions <10% when the concentration is at the limit of
      quantification. A powerful general unknown screening procedure can help to
      confirm suspected interferences. Our results indicate that the specificity of
      screening procedures is questionable for LC-MS/MS analyses performed in the
      selected reaction-monitoring mode and involving a large number of compounds with
      only 1 transition per compound.

PMID- 18635750
TI  - Prognostic value of chromogranin A at admission in critically ill patients: a
      cohort study in a medical intensive care unit.
AB  - BACKGROUND: Risk assessments of patients should be based on objective variables,
      such as biological markers that can be measured routinely. The acute response to
      stress causes the release of catecholamines from the adrenal medulla accompanied
      by chromogranin A (CGA). To date, no study has evaluated the prognostic value of
      CGA in critically ill intensive care unit patients. METHODS: We conducted a
      prospective study of intensive care unit patients by measuring serum
      procalcitonin (PCT), C-reactive protein (CRP), and CGA at the time of admission.
      Univariate and multivariate analyses were performed to evaluate the ability of
      these biomarkers to predict mortality. RESULTS: In 120 consecutive patients, we
      found positive correlations between CGA and the following: CRP (r(2) = 0.216; P =
      0.02), PCT (r(2) = 0.396; P < 0.001), Simplified Acute Physiologic Score II (SAPS
      II) (r(2) = 0.438; P < 0.001), and the Logistic Organ Dysfunction System (LODS)
      score (r(2) = 0.374; P < 0.001). Nonsurvivors had significantly higher CGA and
      PCT concentrations than survivors [median (interquartile range): 293.0 microg/L
      (163.5-699.5 microg/L) vs 86.0 microg/L (53.8-175.3 microg/L) for CGA, and 6.78
      microg/L (2.39-22.92 microg/L) vs 0.54 microg/L (0.16-6.28 microg/L) for PCT; P <
      0.001 for both comparisons]. In a multivariable linear regression analysis,
      creatinine (P < 0.001), age (P < 0.001), and SAPS II (P = 0.002) were the only
      significant independent variables predicting CGA concentration (r(2) = 0.352). A
      multivariate Cox regression analysis identified 3 independent factors predicting
      death: log-normalized CGA concentration [hazard ratio (HR), 7.248; 95% confidence
      interval (CI), 3.004-17.487], SAPS II (HR, 1.046; 95% CI, 1.026-1.067), and
      cardiogenic shock (HR, 3.920; 95% CI, 1.731-8.880). CONCLUSIONS: CGA is a strong
      and independent indicator of prognosis in critically ill nonsurgical patients.

PMID- 18635751
TI  - HPLC with UV or mass spectrometric detection for quantifying endogenous uracil
      and dihydrouracil in human plasma.
AB  - BACKGROUND: We developed and compared 2 different methods for quantifying uracil
      (U) and dihydrouracil (UH(2)) in BSA and human plasma. Special attention was paid
      to the selectivity/specificity and the absence of a matrix effect. The UH(2)/U
      ratio is intended as a biomarker to identify patients with deficiency in 5
      fluorouracil metabolism. METHODS: We quantified U and UH(2) with 2 liquid
      chromatography methods after solid-phase extraction, one with UV detection (LC
      UV) and the other with mass spectrometric detection (LC-MS). We selected 2
      internal standards to prevent the risk of interferences. Separation was achieved
      with a Waters Atlantis dC18 column (LC-MS) or a Waters SymmetryShield RP18 column
      connected with an Atlantis dC18 (LC-UV). Mass spectrometric data were acquired in
      single-ion monitoring mode. RESULTS: Assay imprecision in BSA solution was <15%
      (LC-UV) and <12% (LC-MS); in plasma, assay imprecision was <9.5% and <9.0%,
      respectively. Recoveries were 88.2%-110% (LC-UV) and 94.8%-107% (LC-MS).
      Extraction efficiencies were >or=89.0%. In BSA, the lower limits of
      quantification for U and UH(2) were 2.5 microg/L and 6.25 microg/L, respectively,
      for the LC-UV method and 2.5 microg/L and 3.1 microg/L for LC-MS. The
      corresponding values in plasma were 11.6 microg/L and 21.5 microg/L, and 4.1
      microg/L and 12.1 microg/L. CONCLUSIONS: To estimate endogenous U and UH(2)
      concentrations and their ratio, we recommend the use of a drug-free human plasma
      pool in which baseline U and UH(2) concentrations have previously been measured
      with the standard-addition method. Our LC-MS method, which has the better test
      performance and is useful for measuring UH(2)/U ratios in cancer patients, is
      preferred when this equipment is available.

PMID- 18635752
TI  - Risk of late-life depression across 10 European Union countries: deconstructing
      the education effect.
AB  - OBJECTIVE: Assess influence of education and noneducation-based measures of
      socioeconomic status on depression, illuminating the cumulative and income
      adjusted effects cross-nationally. METHOD: Cross-sectional study of 22,777 men
      and women (50 to 104 years) from 10 European countries. Individual-level data
      were collected from the Survey of Health, Ageing and Retirement in Europe
      (SHARE). RESULTS: Educational attainment was a strong predictor of late-life
      depression across all countries. Depression rates ranged from 18.10% in Denmark
      to 36.84% in Spain, reflecting a North- South gradient. Odds of depression were
      approximately twice as high among adults with less than a high school education
      compared with those of greater educational background (p < .001). Inverse
      association between educational attainment and depression remained significant
      independent of all other sociodemographic variables. DISCUSSION: Socioeconomic
      disparities in depression persist throughout later life. Variation in impact of
      education on depression cross-nationally illuminates need for future research
      into the protective effects of early-life education.

PMID- 18635753
TI  - Participation of K+ channels in the endothelium-dependent and endothelium
      independent components of the relaxant effect of rosuvastatin in rat aortic
      rings.
AB  - Rosuvastatin was tested on rat aortic rings in the presence and absence of K(+)
      channel blockers, mevalonic acid, and inhibitors of nitric oxide, prostaglandins,
      or endothelial-derived hyperpolarizing factor synthesis. The direct vascular
      effects of rosuvastatin were then evaluated by obtaining dose-response curves.
      Rosuvastatin relaxed aortic rings with and, to a lesser degree, without
      endothelium. Under both these conditions this effect was partially inhibited by L
      NAME, tetraethylammonium, apamin + charybdotoxin (only administered together), or
      mevalonic acid. The combination of L-NAME with any of the other 3 treatments
      completely inhibited the effect of rosuvastatin, but indomethacin, clotrimazol,
      glibenclamide, charybdotoxin, or apamin alone had no effect. Therefore, the
      relaxation induced by rosuvastatin, even in the absence of endothelium, is
      partially related to 2 different mechanisms, one that is isoprenoid dependent and
      NO mediated and the other that is tied to the opening of Ca( 2+)-dependent K(+)
      channels of the slow subfamily.

PMID- 18635754
TI  - Efficacy of atorvastatin for achieving cholesterol targets after LDL-cholesterol
      based dose selection in patients with type 2 diabetes.
AB  - We analyzed the feasibility of an intensive lipid-lowering strategy based on a
      starting dose of atorvastatin according to baseline and target low-density
      lipoprotein cholesterol (LDL-C) level (<2.6 mmol/L) in 202 statin-naive patients
      with type 2 diabetes within 24 weeks. They were assigned to receive a daily
      dosage of atorvastatin based on their initial LDL-C levels. The primary endpoint
      was the proportion of patients achieving the LDL-C goal after 24 weeks of
      treatment. No changes were made in prescribed atorvastatin dosage. At the study
      end, 66.5% of the 188 patients completing the trial reached the LDL-C target
      (75%, 67%, 58% and 59% with 10, 20, 40 and 80 mg per day of atorvastatin,
      respectively) reached LDL-C target. Atorvastatin reduced the levels of total
      cholesterol, LDL-C, high density lipoprotein cholesterol (HDL-C) and
      triglycerides by 29%, 35%, 3% and 22%, respectively, and all statin doses were
      well tolerated. Thus, individualizing the starting dose of atorvastatin according
      to baseline and target LDL-C levels, allowed a high proportion of type 2 diabetic
      patients to achieve the target within 24 weeks.

PMID- 18635755
TI  - Direct and acute cardiotoxic effects of ultrafine air pollutants in spontaneously
      hypertensive rats and Wistar--Kyoto rats.
AB  - It is hypothesized that preexisting cardiovascular disease could affect the
      susceptibility to direct and acute cardiotoxic effects of ultrafine air
      pollutants. Ultrafine particles (UFP) isolated from 12.5 mg of diesel particulate
      matter (National Institute of Standards and Technology) were infused into
      isolated Langendorffperfused hearts obtained from spontaneously hypertensive rats
      (SHR) and normotensive control Wistar- Kyoto rats (WKY). Perfusion for 30 minutes
      with UFP reduced cardiac function in both groups-but to a greater extent in WKY.
      In SHR, developed pressure was reduced by 24.1 +/- 4.4% of baseline and maximal
      dP/dt was reduced by 19.8 +/- 4.9%; in WKY, developed pressure was reduced by
      43.5 +/- 7.3% and maximal dP/dt by 41.8 +/- 8.2% (P < .05 for maximal dP/dt in
      SHR vs WKY). Coronary flow was decreased by 30.3% versus 53.7% in SHR versus WKY
      ( P < .05). The results of this study suggest that although UFP depress
      myocardial contractile response and coronary flow in both SHR and WKY the
      underlying hypertension does not necessarily worsen the response.

PMID- 18635756
TI  - The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of
      febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase.
AB  - Febuxostat is a novel nonpurine selective inhibitor of xanthine oxidase, which is
      currently being developed for the management of hyperuricemia in patients with
      gout. The effect of age and gender on the pharmacokinetics, pharmacodynamics, and
      safety of once-daily oral febuxostat 80 mg was assessed in healthy male and
      female subjects after 7 days. Following multiple dosing with febuxostat, there
      were no statistically significant differences in the plasma or urinary
      pharmacokinetic or pharmacodynamic parameters between subjects aged 18 to 40
      years and >or=65 years. Although unbound peak concentration (C(max,u)) and area
      under the concentration-time curve (AUC(24,u)) for febuxostat were higher in
      women as compared with men (31.5 vs 23.6 ng/mL, P <or= .01, and 62.8 vs 53.9 ng x
      h/mL, P <or= .05, for C(max,u) and AUC(24,u), respectively), the differences were
      not considered clinically significant and could be largely accounted for by
      weight differences between male and female subjects. For pharmacodynamic
      parameters, even though the percentage decrease in serum uric acid 24-hour mean
      concentration was slightly greater in women than in men (59% vs 52%, P <or= .01),
      this difference was not considered clinically meaningful. Febuxostat was well
      tolerated in male and female subjects in both age groups. Age or gender had no
      clinically significant effect on the pharmacokinetics, pharmacodynamics, or
      safety of febuxostat. Therefore, febuxostat does not require any dose adjustments
      based on age or gender.

PMID- 18635757
TI  - Practical therapeutic drug management in HIV-infected patients: use of population
      pharmacokinetic models supplemented by individualized Bayesian dose optimization.
AB  - Individualized, model-based, target-oriented optimal concentration-controlled
      dosing of HIV medications can be beneficial to patients for whom there are
      limited dosing guidelines, such as children, adolescents, or patients with
      altered physiologic function. Barriers to this approach include lack of training,
      expertise, and access to appropriate software to assist the clinician. The
      authors present 4 illustrative clinical cases of HIV-infected patients whose
      therapy was optimized using population pharmacokinetic models (here generated
      from published studies) and supplemented by individualized Bayesian adaptive
      control of dosage regimens as implemented in the MM-USCPACK software. These 4
      cases illustrate how clinicians can maximize therapeutic success in (1) patients
      with reduced drug clearance, (2) young adolescents transitioning to adult
      physiology, (3) patients with dose-dependent toxicity, and (4) adolescents with
      limited therapeutic options.

PMID- 18635758
TI  - Glutathione S-transferase A1 genetic variants reduce busulfan clearance in
      children undergoing hematopoietic cell transplantation.
AB  - The effect of glutathione S-transferase variants on pediatric busulfan metabolism
      was investigated by noncompartmental and population pharmacokinetic modeling.
      Twenty-nine children who underwent related or unrelated bone marrow or umbilical
      cord blood hematopoietic cell transplant were retrospectively studied. GSTA1,
      GSTP1, and GSTM1 variants were explored for their effects on busulfan exposures.
      Noncompartmental pharmacokinetic analyses showed that carriers of GSTA1*B had a
      2.6-fold higher busulfan area under the curve and concentration at steady state
      compared with noncarriers (P <or= .01). Population pharmacokinetic modeling
      demonstrated that carriers of GSTA1*B reduced busulfan clearance by 30%. Monte
      Carlo simulations were then performed to assess busulfan dosing regimens based on
      GSTA1 genotypes. Simulations determined that dosing based on GSTA1 genotype,
      weight, and age resulted in fewer children exceeding the upper therapeutic limit
      compared with dosing using age and weight only. Larger, prospective studies are
      needed to confirm these findings.

PMID- 18635759
TI  - Essential cytoplasmic translocation of a cytokine receptor-assembled signaling
      complex.
AB  - Cytokine signaling is thought to require assembly of multicomponent signaling
      complexes at cytoplasmic segments of membrane-embedded receptors, in which
      receptor-proximal protein kinases are activated. Indeed, CD40, a tumor necrosis
      factor receptor (TNFR) family member, forms a complex containing adaptor
      molecules TRAF2 and TRAF3, ubiquitin-conjugating enzyme Ubc13, cellular inhibitor
      of apoptosis proteins 1 and 2 (c-IAP1/2), IkappaB kinase regulatory subunit
      IKKgamma (also called NEMO), and mitogen-activated protein kinase (MAPK) kinase
      kinase MEKK1 upon ligation. TRAF2, Ubc13, and IKKgamma were required for complex
      assembly and activation of MEKK1 and MAPK cascades. However, these kinases were
      not activated unless the multicomponent signaling complex translocated from CD40
      to the cytosol upon c-IAP1/2-induced degradation of TRAF3. This two-stage
      signaling mechanism may apply to other innate immune receptors, accounting for
      spatial and temporal separation of MAPK and IKK signaling.

PMID- 18635760
TI  - Plant immunity requires conformational changes [corrected] of NPR1 via S
      nitrosylation and thioredoxins.
AB  - Changes in redox status have been observed during immune responses in different
      organisms, but the associated signaling mechanisms are poorly understood. In
      plants, these redox changes regulate the conformation of NPR1, a master regulator
      of salicylic acid (SA)-mediated defense genes. NPR1 is sequestered in the
      cytoplasm as an oligomer through intermolecular disulfide bonds. We report that S
      nitrosylation of NPR1 by S-nitrosoglutathione (GSNO) at cysteine-156 facilitates
      its oligomerization, which maintains protein homeostasis upon SA induction.
      Conversely, the SA-induced NPR1 oligomer-to-monomer reaction is catalyzed by
      thioredoxins (TRXs). Mutations in both NPR1 cysteine-156 and TRX compromised NPR1
      mediated disease resistance. Thus, the regulation of NPR1 is through the opposing
      action of GSNO and TRX. These findings suggest a link between pathogen-triggered
      redox changes and gene regulation in plant immunity.

PMID- 18635762
TI  - Engaging Russian scientists.

PMID- 18635761
TI  - Ferruginous conditions dominated later neoproterozoic deep-water chemistry.
AB  - Earth's surface chemical environment has evolved from an early anoxic condition
      to the oxic state we have today. Transitional between an earlier Proterozoic
      world with widespread deep-water anoxia and a Phanerozoic world with large oxygen
      utilizing animals, the Neoproterozoic Era [1000 to 542 million years ago (Ma)]
      plays a key role in this history. The details of Neoproterozoic Earth surface
      oxygenation, however, remain unclear. We report that through much of the later
      Neoproterozoic (<742 +/- 6 Ma), anoxia remained widespread beneath the mixed
      layer of the oceans; deeper water masses were sometimes sulfidic but were mainly
      Fe2+-enriched. These ferruginous conditions marked a return to ocean chemistry
      not seen for more than one billion years of Earth history.

PMID- 18635763
TI  - Climate change. Bush takes a final swipe, and salute, at CO2 emission curbs.

PMID- 18635764
TI  - Research ethics. Old samples trip up Tokyo team.

PMID- 18635765
TI  - Defense research. New policy tries to ease security restrictions.

PMID- 18635766
TI  - Medicine. Stalled trial for autism highlights dilemma of alternative treatments.

PMID- 18635767
TI  - Paleoceanography. Caribbean megaeruptions drove a global ocean crisis.

PMID- 18635768
TI  - Nuclear physics. Two U.S. labs vie for long-delayed exotic nuclei source.

PMID- 18635769
TI  - Sociology. Survey finds citations growing narrower as journals move online.

PMID- 18635770
TI  - Agricultural research. Reinventing rice to feed the world.

PMID- 18635771
TI  - Agricultural research. Sowing the seeds of expertise.

PMID- 18635772
TI  - Genetics. Simple sleepers.

PMID- 18635773
TI  - Acoustics '08. Sound science maps Venetian canals and Peruvian ruins.

PMID- 18635774
TI  - Acoustics '08. Ultrasound uses in medicine heat up.

PMID- 18635775
TI  - Acoustics '08. Snapshots from the meeting.

PMID- 18635776
TI  - Acoustics '08. Listening to distant ice crack.

PMID- 18635777
TI  - The cost of conservation.

PMID- 18635778
TI  - Conservation with caveats.

PMID- 18635779
TI  - Comment on "A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide
      assimilation pathway in Archaea".
AB  - Berg et al. (Reports, 14 December 2007, p. 1782) reported the discovery of an
      autotrophic carbon dioxide-fixation pathway in Archaea and implicated a
      substantial role of this pathway in global carbon cycling based on sequence
      analysis of Global Ocean Sampling data. We question the validity of the latter
      claim.

PMID- 18635780
TI  - Ecology. Assisted colonization and rapid climate change.

PMID- 18635781
TI  - Neuroscience. Vertebrate vocalizations.

PMID- 18635782
TI  - Climate. Was the Younger Dryas global?

PMID- 18635783
TI  - Materials science. Tracking corrosion cracking.

PMID- 18635784
TI  - Developmental biology. Grasping limb patterning.

PMID- 18635785
TI  - Applied physics. Focus on x-ray diffraction.

PMID- 18635786
TI  - Climate change. A hotter greenhouse?

PMID- 18635787
TI  - Drug resistance. Deadly defiance. Introduction to special issue.

PMID- 18635788
TI  - The bacteria fight back.

PMID- 18635789
TI  - Collateral damage. The rise of resistant C. difficile.

PMID- 18635790
TI  - Trench warfare in a battle with TB.

PMID- 18635791
TI  - Anti-TB drugs: and then there were none.

PMID- 18635792
TI  - Antibiotics and antibiotic resistance genes in natural environments.
AB  - The large majority of antibiotics currently used for treating infections and the
      antibiotic resistance genes acquired by human pathogens each have an
      environmental origin. Recent work indicates that the function of these elements
      in their environmental reservoirs may be very distinct from the "weapon-shield"
      role they play in clinical settings. Changes in natural ecosystems, including the
      release of large amounts of antimicrobials, might alter the population dynamics
      of microorganisms, including selection of resistance, with consequences for human
      health that are difficult to predict.

PMID- 18635793
TI  - Outwitting multidrug resistance to antifungals.
AB  - The economic cost of fungal infection and its mortality associated with multidrug
      resistance remain unacceptably high. Recent understanding of the transcriptional
      regulation of plasma membrane efflux pumps of modest specificity provides new
      avenues for the development of broad-spectrum fungicides. Together with improved
      diagnosis and indirect intervention via inhibition of the energy supply for drug
      efflux, we envisage multifunctional azole analogs that inhibit not only
      ergosterol biosynthesis and drug efflux-pump activity but also activation of the
      transcriptional machinery that induces drug efflux-pump expression.

PMID- 18635794
TI  - Ice scour disturbance in Antarctic waters.
AB  - The West Antarctic Peninsula is one of the fastest warming regions on Earth, and,
      as a consequence, most maritime glaciers and ice shelves in the region have
      significantly retreated over the past few decades. We collected a multiyear data
      set on ice scouring frequency from Antarctica by using unique experimental
      markers and scuba diving surveys. We show that the annual intensity of ice
      scouring is negatively correlated with the duration of the winter fast ice
      season. Because fast ice extent and duration is currently in decline in the
      region after recent rapid warming, it is likely that marine benthic communities
      are set for even more scouring in the near future.

PMID- 18635795
TI  - Identification of SLEEPLESS, a sleep-promoting factor.
AB  - Sleep is an essential process conserved from flies to humans. The importance of
      sleep is underscored by its tight homeostatic control. Through a forward genetic
      screen, we identified a gene, sleepless, required for sleep in Drosophila. The
      sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored
      protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a
      moderate reduction in SLEEPLESS had minimal effects on baseline sleep but
      markedly reduced the amount of recovery sleep after sleep deprivation. Genetic
      and molecular analyses revealed that quiver, a mutation that impairs Shaker
      dependent potassium current, is an allele of sleepless. Consistent with this
      finding, Shaker protein levels were reduced in sleepless mutants. We propose that
      SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane
      excitability.

PMID- 18635796
TI  - High-resolution scanning x-ray diffraction microscopy.
AB  - Coherent diffractive imaging (CDI) and scanning transmission x-ray microscopy
      (STXM) are two popular microscopy techniques that have evolved quite
      independently. CDI promises to reach resolutions below 10 nanometers, but the
      reconstruction procedures put stringent requirements on data quality and sample
      preparation. In contrast, STXM features straightforward data analysis, but its
      resolution is limited by the spot size on the specimen. We demonstrate a
      ptychographic imaging method that bridges the gap between CDI and STXM by
      measuring complete diffraction patterns at each point of a STXM scan. The high
      penetration power of x-rays in combination with the high spatial resolution will
      allow investigation of a wide range of complex mesoscopic life and material
      science specimens, such as embedded semiconductor devices or cellular networks.

PMID- 18635797
TI  - Observations of intergranular stress corrosion cracking in a grain-mapped
      polycrystal.
AB  - Nondestructive three-dimensional mapping of grain shape, crystallographic
      orientation, and grain boundary geometry by diffraction contrast tomography (DCT)
      provides opportunities for the study of the interaction between intergranular
      stress corrosion cracking and microstructure. A stress corrosion crack was grown
      through a volume of sensitized austenitic stainless steel mapped with DCT and
      observed in situ by synchrotron tomography. Several sensitization-resistant crack
      bridging boundaries were identified, and although they have special geometric
      properties, they are not the twin variant boundaries usually maximized during
      grain boundary engineering.

PMID- 18635798
TI  - Measurement of the elastic properties and intrinsic strength of monolayer
      graphene.
AB  - We measured the elastic properties and intrinsic breaking strength of free
      standing monolayer graphene membranes by nanoindentation in an atomic force
      microscope. The force-displacement behavior is interpreted within a framework of
      nonlinear elastic stress-strain response, and yields second- and third-order
      elastic stiffnesses of 340 newtons per meter (N m(-1)) and -690 Nm(-1),
      respectively. The breaking strength is 42 N m(-1) and represents the intrinsic
      strength of a defect-free sheet. These quantities correspond to a Young's modulus
      of E = 1.0 terapascals, third-order elastic stiffness of D = -2.0 terapascals,
      and intrinsic strength of sigma(int) = 130 gigapascals for bulk graphite. These
      experiments establish graphene as the strongest material ever measured, and show
      that atomically perfect nanoscale materials can be mechanically tested to
      deformations well beyond the linear regime.

PMID- 18635799
TI  - Patagonian glacier response during the late glacial-Holocene transition.
AB  - Whether cooling occurred in the Southern Hemisphere during the Younger Dryas (YD)
      is key to understanding mechanisms of millennial climate change. Although
      Southern Hemisphere records do not reveal a distinct climate reversal during the
      late glacial period, many mountain glaciers readvanced. We show that the Puerto
      Bandera moraine (50 degrees S), which records a readvance of the Southern
      Patagonian Icefield (SPI), formed at, or shortly after, the end of the YD. The
      exposure age (10.8 +/- 0.5 thousand years ago) is contemporaneous with the
      highest shoreline of Lago Cardiel (49 degrees S), which records peak
      precipitation east of the Andes since 13 thousand years ago. Absent similar
      moraines west of the Andes, these data indicate an SPI response to increased
      amounts of easterly-sourced precipitation-reflecting changes in the Southern
      Westerly circulation-rather than regional cooling.

PMID- 18635800
TI  - Electronic publication and the narrowing of science and scholarship.
AB  - Online journals promise to serve more information to more dispersed audiences and
      are more efficiently searched and recalled. But because they are used differently
      than print-scientists and scholars tend to search electronically and follow
      hyperlinks rather than browse or peruse-electronically available journals may
      portend an ironic change for science. Using a database of 34 million articles,
      their citations (1945 to 2005), and online availability (1998 to 2005), I show
      that as more journal issues came online, the articles referenced tended to be
      more recent, fewer journals and articles were cited, and more of those citations
      were to fewer journals and articles. The forced browsing of print archives may
      have stretched scientists and scholars to anchor findings deeply into past and
      present scholarship. Searching online is more efficient and following hyperlinks
      quickly puts researchers in touch with prevailing opinion, but this may
      accelerate consensus and narrow the range of findings and ideas built upon.

PMID- 18635801
TI  - The evolution and distribution of species body size.
AB  - The distribution of species body size within taxonomic groups exhibits a heavy
      right tail extending over many orders of magnitude, where most species are much
      larger than the smallest species. We provide a simple model of cladogenetic
      diffusion over evolutionary time that omits explicit mechanisms for interspecific
      competition and other microevolutionary processes, yet fully explains the shape
      of this distribution. We estimate the model's parameters from fossil data and
      find that it robustly reproduces the distribution of 4002 mammal species from the
      late Quaternary. The observed fit suggests that the asymmetric distribution
      arises from a fundamental trade-off between the short-term selective advantages
      (Cope's rule) and long-term selective risks of increased species body size in the
      presence of a taxon-specific lower limit on body size.

PMID- 18635802
TI  - Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains.
AB  - The atypical cadherin Fat acts as a receptor for a signaling pathway that
      regulates growth, gene expression, and planar cell polarity. Genetic studies in
      Drosophila identified the four-jointed gene as a regulator of Fat signaling. We
      show that four-jointed encodes a protein kinase that phosphorylates serine or
      threonine residues within extracellular cadherin domains of Fat and its
      transmembrane ligand, Dachsous. Four-jointed functions in the Golgi and is the
      first molecularly defined kinase that phosphorylates protein domains destined to
      be extracellular. An acidic sequence motif (Asp-Asn-Glu) within Four-jointed was
      essential for its kinase activity in vitro and for its biological activity in
      vivo. Our results indicate that Four-jointed regulates Fat signaling by
      phosphorylating cadherin domains of Fat and Dachsous as they transit through the
      Golgi.

PMID- 18635803
TI  - Signal-mediated dynamic retention of glycosyltransferases in the Golgi.
AB  - Golgi-resident glycosyltransferases are a family of enzymes that sequentially
      modify glycoproteins in a subcompartment-specific manner. These type II integral
      membrane proteins are characterized by a short cytoplasmically exposed amino
      terminal tail and a luminal enzymatic domain. The cytoplasmic tails play a role
      in the localization of glycosyltransferases, and coat protein complex I (COPI)
      vesicle-mediated retrograde transport is also involved in their Golgi
      localization. However, the tails of these enzymes lack known COPI-binding motifs.
      Here, we found that Vps74p bound to a pentameric motif present in the cytoplasmic
      tails of the majority of yeast Golgi-localized glycosyltransferases, as well as
      to COPI. We propose that Vps74p maintains the steady-state localization of Golgi
      glycosyltransferases dynamically, by promoting their incorporation into COPI
      coated vesicles.

PMID- 18635804
TI  - Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and
      eomesodermin.
AB  - When intracellular pathogens invade mammalian hosts, naive CD8+ T cells
      differentiate into cytotoxic killers, which lyse infected target cells and
      secrete cytokines that activate intracellular microbicides. We show that CD8+ T
      cells deficient in the transcription factors T-bet and eomesodermin (Eomes) fail
      to differentiate into functional killers required for defense against lymphocytic
      choriomeningitis virus. Instead, virus-specific CD8+ T cells lacking both T-bet
      and Eomes differentiate into an interleukin-17-secreting lineage, reminiscent of
      the helper T cell fate that has been implicated in autoimmunity and extracellular
      microbial defense. Upon viral infection, mice with T cells lacking both T-bet and
      Eomes develop a CD8+ T cell-dependent, progressive inflammatory and wasting
      syndrome characterized by multi-organ infiltration of neutrophils. T-bet and
      Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of
      intracellular rather than extracellular destruction.

PMID- 18635805
TI  - Riboswitches in eubacteria sense the second messenger cyclic di-GMP.
AB  - Cyclic di-guanosine monophosphate (di-GMP) is a circular RNA dinucleotide that
      functions as a second messenger in diverse species of bacteria to trigger wide
      ranging physiological changes, including cell differentiation, conversion between
      motile and biofilm lifestyles, and virulence gene expression. However, the
      mechanisms by which cyclic di-GMP regulates gene expression have remained a
      mystery. We found that cyclic di-GMP in many bacterial species is sensed by a
      riboswitch class in messenger RNA that controls the expression of genes involved
      in numerous fundamental cellular processes. A variety of cyclic di-GMP regulons
      are revealed, including some riboswitches associated with virulence gene
      expression, pilus formation, and flagellum biosynthesis. In addition, sequences
      matching the consensus for cyclic di-GMP riboswitches are present in the genome
      of a bacteriophage.

PMID- 18635806
TI  - Bottom-up dependent gating of frontal signals in early visual cortex.
AB  - The frontal eye field (FEF) is one of several cortical regions thought to
      modulate sensory inputs. Moreover, several hypotheses suggest that the FEF can
      only modulate early visual areas in the presence of a visual stimulus. To test
      for bottom-up gating of frontal signals, we microstimulated subregions in the FEF
      of two monkeys and measured the effects throughout the brain with functional
      magnetic resonance imaging. The activity of higher-order visual areas was
      strongly modulated by FEF stimulation, independent of visual stimulation. In
      contrast, FEF stimulation induced a topographically specific pattern of
      enhancement and suppression in early visual areas, but only in the presence of a
      visual stimulus. Modulation strength depended on stimulus contrast and on the
      presence of distractors. We conclude that bottom-up activation is needed to
      enable top-down modulation of early visual cortex and that stimulus saliency
      determines the strength of this modulation.

PMID- 18635807
TI  - Evolutionary origins for social vocalization in a vertebrate hindbrain-spinal
      compartment.
AB  - The macroevolutionary events leading to neural innovations for social
      communication, such as vocalization, are essentially unexplored. Many fish
      vocalize during female courtship and territorial defense, as do amphibians,
      birds, and mammals. Here, we map the neural circuitry for vocalization in larval
      fish and show that the vocal network develops in a segment-like region across the
      most caudal hindbrain and rostral spinal cord. Taxonomic analysis demonstrates a
      highly conserved pattern between fish and all major lineages of vocal tetrapods.
      We propose that the vocal basis for acoustic communication among vertebrates
      evolved from an ancestrally shared developmental compartment already present in
      the early fishes.

PMID- 18635808
TI  - Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and
      their unaffected relatives.
AB  - Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and
      behaviors associated with underlying dysregulation of frontostriatal circuitry.
      Central to neurobiological models of OCD is the orbitofrontal cortex, a neural
      region that facilitates behavioral flexibility after negative feedback (reversal
      learning). We identified abnormally reduced activation of several cortical
      regions, including the lateral orbitofrontal cortex, during reversal learning in
      OCD patients and their clinically unaffected close relatives, supporting the
      existence of an underlying previously undiscovered endophenotype for this
      disorder.

PMID- 18635810
TI  - Selective accumulation of virus-specific CD8+ T cells with unique homing
      phenotype within the human bone marrow.
AB  - The bone marrow plays a unique role within the immune system. We compared the
      phenotype and function of virus-specific CD8(+) T cells from matched samples of
      human peripheral blood and bone marrow. Analysis of virus-specific memory CD8(+)
      T cells showed widely divergent partition of antigen-specific populations between
      blood and bone marrow. T cells specific for Epstein-Barr virus (EBV) lytic
      antigens were enriched 3-fold in marrow compared with blood, whereas the response
      to EBV latent epitopes was equivalent between the 2 compartments. No difference
      in EBV viral load or expression of the EBV lytic protein was observed between
      blood and bone marrow. In direct contrast, although cytomegalo-virus (CMV)
      specific T cells were the largest virus-specific population within peripheral
      blood, they were reduced by 60% within marrow. Bone marrow T cells were found to
      exhibit a unique CCR5(+)CXCR6(+)CXCR3(-) homing phenotype which has not been
      observed on T cells from other secondary lymphoid organs or peripheral organs.
      Expression of CCR5 and CXCR6 was higher on EBV-specific T cells within peripheral
      blood compared with CMV-specific populations. These observations identify a novel
      bone marrow homing phenotype for CD8(+) memory T cells, which necessitates a
      reevaluation of the magnitude of antigen-specific populations within the lymphoid
      system.

PMID- 18635811
TI  - Carboxypeptidase A5 identifies a novel mast cell lineage in the zebrafish
      providing new insight into mast cell fate determination.
AB  - Mast cells (MCs) play critical roles in allergy and inflammation, yet their
      development remains controversial due to limitations posed by traditional animal
      models. The zebrafish provides a highly efficient system for studying vertebrate
      hematopoiesis. We have identified zebrafish MCs in the gill and intestine, which
      resemble their mammalian counterparts both structurally and functionally.
      Carboxypeptidase A5 (cpa5), a MC-specific enzyme, is expressed in zebrafish blood
      cells beginning at 24 hours post fertilization (hpf). At 28 hpf, colocalization
      is observed with pu.1, mpo, l-plastin, and lysozyme C, but not fms or cepbalpha,
      identifying these early MCs as a distinct myeloid population arising from a
      common granulocyte/monocyte progenitor. Morpholino "knock-down" studies
      demonstrate that transcription factors gata-2 and pu.1, but not gata-1 or fog-1,
      are necessary for early MC development. These studies validate the zebrafish as
      an in vivo tool for studying MC ontogeny and function with future capacity for
      modeling human MC diseases.

PMID- 18635812
TI  - Combined functional and molecular analysis of tumor cell signaling defines 2
      distinct myeloma subgroups: Akt-dependent and Akt-independent multiple myeloma.
AB  - Although the phosphatidylinositide 3-kinase (PI3K)/Akt pathway has been reported
      to contribute to the malignant growth of multiple myeloma (MM), the true
      relevance of Akt kinases for this disease is still unclear. In particular,
      functional analyses in primary tumor cells and genetic target validation
      experiments are missing. Here, we used combined functional and molecular analyses
      to determine the importance of Akt activity in a large panel of primary MM
      samples and in MM cell lines. Akt down-regulation with isoform-specific siRNA
      constructs or with an Akt1/2-specific pharmacologic inhibitor strongly induced
      apoptosis in approximately half of the primary MM samples analyzed. Sensitivity
      to Akt inhibition strongly correlated with the activation status of Akt as
      determined by immunohistochemistry, phospho-Akt-specific flow cytometry, and
      Western analysis. Additional blockade of the MAPK and the IL-6R/STAT3 pathways
      was often not sufficient to decrease the viability of MM cells resilient to Akt
      inhibition. Taken together, these experiments led to the identification of 2
      myeloma subgroups: Akt-dependent and Akt-independent MM.

PMID- 18635813
TI  - Acute exercise decreases airway inflammation, but not responsiveness, in an
      allergic asthma model.
AB  - Previous studies have suggested that the asthmatic responses of airway
      inflammation, remodeling, and hyperresponsiveness (AHR) are interrelated; in this
      study, we used exercise to examine the nature of this interrelationship. Mice
      were sensitized and challenged with ovalbumin (OVA); mice were then exercised via
      running on a motorized treadmill at a moderate intensity. Data indicate that,
      within the lungs of OVA-treated mice, exercise attenuated the production of
      inflammatory mediators, including chemokines KC, RANTES, and MCP-1 and IL
      12p40/p80. Coordinately, OVA-treated and exercised mice displayed decreases in
      leukocyte infiltration, including eosinophils, as compared with sedentary
      controls. Results also show that a single bout of exercise significantly
      decreased phosphorylation of the NFkappaB p65 subunit, which regulates the gene
      expression of a wide variety of inflammatory mediators. In addition, OVA-treated
      and exercised mice exhibited decreases in the levels of Th2-derived cytokines IL
      5 and IL-13 and the prostaglandin PGE(2), as compared with sedentary controls. In
      contrast, results show that a single bout of exercise had no effect on AHR in OVA
      treated mice challenged with increasing doses of aerosolized methacholine (0-50
      mg/ml) as compared with sedentary mice. Exercise also had no effect on epithelial
      cell hypertrophy, mucus production, or airway wall thickening in OVA-treated mice
      as compared with sedentary controls. These findings suggest that a single bout of
      aerobic exercise at a moderate intensity attenuates airway inflammation but not
      AHR or airway remodeling in OVA-treated mice. The implication of these findings
      for the interrelationship between airway inflammation, airway remodeling, and AHR
      is discussed.

PMID- 18635814
TI  - Overexpression of Sprouty 2 in mouse lung epithelium inhibits urethane-induced
      tumorigenesis.
AB  - Members of the Sprouty family encode novel proteins that are thought to function
      primarily as intracellular antagonists of the Ras-signaling pathway. Increased
      Ras signaling is a critical characteristic of human lung adenocarcinoma, the most
      common type of non-small cell lung cancer. Sprouty 2 is expressed in the lung
      epithelium, the tissue layer from which lung cancers arise. We hypothesized that
      overexpression of Sprouty 2 in the distal lung epithelium would inhibit lung
      tumorigenesis. To test the hypothesis, the consequences of overexpressing Sprouty
      2 in the distal lung epithelium on urethane-induced mouse lung tumorigenesis were
      determined. Urethane is a chemical carcinogen found in tobacco smoke that causes
      activating mutations in Kras and induces lung tumors in mice. Sprouty 2
      overexpressor mice developed significantly fewer lung tumors compared with their
      littermate controls (13.2 +/- 1.1 versus 18.1 +/- 1.3, P = 0.006). Tumor diameter
      was also significantly smaller in Sprouty 2 overexpressors (0.85 mm +/- 0.03
      versus 0.95 mm +/- 0.02, P = 0.005). Sprouty 2 overexpression did not alter Kras
      mutational frequencies in urethane-induced tumors, suggesting that the tumor
      suppressing effect of Sprouty 2 overexpression acts at a stage after Kras
      mutation, perhaps by interfering with receptor tyrosine kinase-induced signaling.
      These results demonstrate that Sprouty 2 overexpression inhibited both tumor
      initiation and subsequent tumor growth.

PMID- 18635815
TI  - Adjuvant and anti-inflammatory properties of cigarette smoke in murine allergic
      airway inflammation.
AB  - The impact of cigarette smoke on allergic asthma remains controversial both
      clinically and experimentally. The objective of this study was to investigate, in
      a murine model, how cigarette smoke affects immune inflammatory processes
      elicited by a surrogate allergen. In our experimental design, mice were
      concurrently exposed to cigarette smoke and ovalbumin (OVA), an innocuous antigen
      that, unless introduced in the context of an adjuvant, induces inhalation
      tolerance. We show that cigarette smoke exposure has adjuvant properties,
      allowing for allergic mucosal sensitization to OVA. Specifically, concurrent
      exposure to cigarette smoke and OVA for 2 weeks led to airway eosinophilia and
      goblet cell hyperplasia. In vivo OVA recall challenge 1 month after the last
      smoke exposure showed that concurrent exposure to OVA and cigarette smoke induced
      antigen-specific memory. Robust eosinophilia and OVA-specific IgG1 and IgE
      characterized the ensuing inflammatory response. Mechanistically, allergic
      sensitization was, in part, granulocyte macrophage colony-stimulating factor (GM
      CSF) dependent, as a significant reduction in BAL eosinophilia was observed in
      mice treated with an anti-GM-CSF antibody. Of note, continuous smoke exposure
      attenuated the OVA recall response; decreased airway eosinophilia was observed in
      mice continuously exposed to cigarette smoke compared with mice that ceased the
      smoke exposure protocol. In conclusion, we demonstrate experimentally that while
      cigarette smoke acts as an adjuvant allowing for allergic sensitization, it also
      attenuates the ensuing eosinophilic inflammatory response.

PMID- 18635816
TI  - Oxidative stress causes IL8 promoter hyperacetylation in cystic fibrosis airway
      cell models.
AB  - Dysregulated inflammation has been implicated in cystic fibrosis (CF) airway
      pathophysiology. The expression of inflammatory genes, like interleukin 8 (IL8),
      involves chromatin remodeling through histone acetylation. Inflammatory gene
      hyperacetylation could explain inflammatory mediator dysregulation seen in CF
      airways. CF airways are exposed to high levels of oxidative stress, and oxidative
      stress increases histone acetylation and inflammatory gene transcription. Loss of
      cystic fibrosis transmembrane conductance regulator (CFTR) may even reduce
      protection against oxidative stress. Consequently, increasing oxidative stress
      would likely lead to an imbalance of histone acetyl-transferase (HAT) and
      deacetylase (HDAC) stoichiometry and contribute to the heightened inflammatory
      response seen in the CF airway. We hypothesize that oxidative stress in CF
      airways causes increased acetylation of inflammatory gene promoters, contributing
      to transcriptional activity of these loci. Messenger RNA levels of IL8, IL6,
      CXCL1, CXCL2, CXCL3, and IL1 are significantly elevated in CF epithelial cell
      models. Histone H4 acetylation is lower at the IL8 promoter of the non-CF cell
      lines than the CF models. The reducing agent N-acetyl-cysteine decreases IL8
      message and promoter H4 acetylation to non-CF levels, suggesting that oxidative
      stress contributes to IL8 expression in these models. H(2)O(2) treatment causes
      increased IL-8 acetylation and mRNA in all cells, but less in the CF-model cells.
      Together these data suggest a model in which cells without functional CFTR are
      under increased oxidative stress. Our data suggest intrinsic alterations in the
      HAT/HDAC balance in CFTR-deficient cells, and that oxidative stress contributes
      to this alteration.

PMID- 18635817
TI  - Tubulin acetylation and histone deacetylase 6 activity in the lung under cyclic
      load.
AB  - Previous studies from our lab have demonstrated that upon exposure to physiologic
      levels of cyclic stretch, alveolar epithelial cells demonstrate a significant
      decrease in the amount of polymerized tubulin (Geiger et al., Gene Therapy
      2006;13:725-731). However, not all microtubules are disassembled, although the
      mechanisms or implications of this were unknown. Using immunofluorescence
      microscopy, Western blotting, and immunohistochemistry approaches, we have
      compared the levels of acetylated tubulin in stretched and unstretched A549 cells
      and in murine lungs. In cultured cells exposed to cyclic stretch (10% change in
      basement membrane surface area at 0.25 Hz), nearly all of the remaining
      microtubules were acetylated, as demonstrated using immunofluorescence
      microscopy. In murine lungs ventilated for 20 minutes at 12 to 20 ml/kg followed
      by 48 hours of spontaneous breathing or for 3 hours at 16 to 40 ml/kg, levels of
      acetylated tubulin were increased in the peripheral lung. In both our in vitro
      and in vivo studies, we have found that mild to moderate levels of cyclic stretch
      significantly increases tubulin acetylation in a magnitude- and duration
      dependent manner. This appears to be due to a decrease in histone deacetylase 6
      activity (HDAC6), the major tubulin deacetylase. Since it has been previously
      shown that acetylated microtubules are positively correlated to a more stable
      population of microtubules, this result suggests that microtubule stability may
      be increased by cyclic stretch, and that tubulin acetylation is one way in which
      cells respond to changes in exogenous mechanical forces.

PMID- 18635818
TI  - Effects of six APOA5 variants, identified in patients with severe
      hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor
      binding.
AB  - OBJECTIVE: The purpose of this study was to identify rare APOA5 variants in 130
      severe hypertriglyceridemic patients by sequencing, and to test their
      functionality, since no patient recall was possible. METHODS AND RESULTS: We
      studied the impact in vitro on LPL activity and receptor binding of 3 novel
      heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the
      previously reported -G185C, -Q139X, -Q148X, and a novel construct -Delta139 to
      147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and 
      C185 showed reduced LPL activation (-25% [P=0.005], -36% [P<0.0001], and -23%
      [P=0.02]), respectively). ApoAV-C271, -X139, -X148, and Delta139 to 147 had
      little affect on LPL activity, but apoAV-X139, -X148, and -C271 showed no binding
      to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no LPL
      and APOC2 mutations, the H321L carrier was heterozygous for LPL P207L. The E255G
      carrier was homozygous for LPL W86G, yet only experienced severe
      hypertriglyceridemia when pregnant. CONCLUSIONS: The in vitro determined function
      of these apoAV variants only partly explains the high TG levels seen in carriers.
      Their occurrence in the homozygous state, coinheritance of LPL variants or common
      APOA5 TG-raising variant in trans, appears to be essential for their phenotypic
      expression.

PMID- 18635819
TI  - Retraction: Platelet-derived RANTES mediates hypercholesterolemia-induced
      superoxide production and endothelial dysfunction.

PMID- 18635820
TI  - 12/15-Lipoxygenase activity increases the degradation of macrophage ATP-binding
      cassette transporter G1.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of 12/15
      lipoxygenase (12/15LO) in macrophage ABCG1 expression and function associated
      with cholesterol efflux. METHODS AND RESULTS: 12/15LO was stably overexpressed in
      J774 macrophages. 12/15LO-overexpressing macrophages had a 30% reduction in HDL
      mediated cholesterol efflux, corresponding with significantly reduced ABCG1
      protein expression. Treatment of 12/15LO-overexpressing macrophages with a
      12/15LO ribozyme to reduce 12/15LO restored HDL-mediated efflux and ABCG1 protein
      expression. Treating macrophages with 12/15LO unsaturated fatty acid substrates
      or eicosanoid products also reduced HDL-mediated cholesterol efflux.
      Additionally, both 12/15LO overexpression in macrophages and incubation of
      macrophages with eicosanoids reduced ABCG1 protein, but not mRNA, expression.
      However, incubation of macrophages with linoleic or arachidonic acids
      significantly reduced both ABCG1 mRNA and protein expression, suggesting that
      12/15LO substrates and eicosanoid products differentially regulate ABCG1
      expression. 12/15LO fatty acids did not decrease ABCG1 translation; however,
      12/15LO fatty acids increased ABCG1 degradation when blocked by cyclohexidmide.
      ABCG1 degradation may be regulated through posttranslational modifications.
      Treatment with the 12/15LO eicosanoid product 12SHETE increased serine
      phosphorylation of ABCG1. CONCLUSIONS: We conclude that serine phosphorylation
      may increase the degradation rate of ABCG1, and as a result cause macrophage
      cholesterol accumulation. These findings provide evidence that 12/15LO activity
      in the vessel wall contributes to atherogenesis by impairing the macrophage ABCG1
      cholesterol efflux pathway.

PMID- 18635822
TI  - Myofibrillar architecture in engineered cardiac myocytes.
AB  - Morphogenesis is often considered a function of transcriptional synchrony and the
      spatial limits of diffusing mitogens; however, physical constrainment by the cell
      microenvironment represents an additional mechanism for regulating self-assembly
      of subcellular structures. We asked whether myocyte shape is a distinct signal
      that potentiates the organization of myofibrillar arrays in cardiac muscle
      myocytes. We engineered the shape of neonatal rat ventricular myocytes by
      culturing them on microfabricated fibronectin islands, where they spread and
      assumed the shape of the island. Myofibrillogenesis followed, both spatially and
      temporally, the assembly of unique actin networks whose architecture was
      predictable given the shape of the island. Subsequently, the z lines of the
      sarcomeres aligned and registered in distinct patterns in different regions of
      the myocytes in such a way that orthogonal axes of contraction could be
      distinctly engineered. These data suggest that physical constrainment of muscle
      cells by extracellular matrix may be an important regulator of myofibrillar
      organization.

PMID- 18635821
TI  - Protein kinase G phosphorylates soluble guanylyl cyclase on serine 64 and
      inhibits its activity.
AB  - OBJECTIVE: Binding of nitric oxide (NO) to soluble guanylyl cyclase (sGC) leads
      to increased cGMP synthesis that activates cGMP-dependent protein kinase (PKG).
      Herein, we tested whether sGC activity is regulated by PKG. METHODS AND RESULTS:
      Overexpression of a constitutively active form of PKG (DeltaPKG) stimulated (32)P
      incorporation into the alpha1 subunit. Serine to alanine mutation of putative
      sites revealed that Ser64 is the main phosphorylation site for PKG. Using a
      phospho-specific antibody we observed that endogenous sGC phosphorylation on Ser
      64 increases in cells and tissues exposed to NO, in a PKG-inhibitable manner.
      Wild-type (wt) sGC coexpressed with DeltaPKG exhibited lower basal and NO
      stimulated cGMP accumulation, whereas the S64A alpha1/beta1 sGC was resistant to
      the PKG-induced reduction in activity. Using purified sGC we observed that the
      S64D alpha1 phosphomimetic /beta1 dimer exhibited lower Vmax; moreover, the
      decrease in Km after NO stimulation was less pronounced in S64D alpha1/beta1
      compared to wild-type sGC. Expression of a phosphorylation-deficient sGC showed
      enhanced responsiveness to endothelium-derived NO, reduced desensitization to
      acute NO exposure, and allowed for greater VASP phosphorylation. CONCLUSIONS: We
      conclude that PKG phosphorylates sGC on Ser64 of the alpha1 subunit and that
      phosphorylation inhibits sGC activity, establishing a negative feedback loop.

PMID- 18635823
TI  - Transcriptional regulation during development of the ductus arteriosus.
AB  - The ductus arteriosus is a specialized blood vessel containing highly
      differentiated and contractile vascular smooth muscle, derived largely from
      neural crest cells, that is essential for fetal life but typically closes after
      birth. Impaired development of the ductus arteriosus or disruption of signaling
      pathways that initiate postnatal closure can result in persistent patency of the
      ductus arteriosus, the third most common congenital heart defect. We found that
      Tfap2beta, a transcription factor associated with patent ductus arteriosus in
      humans, was uniquely expressed in mouse ductal smooth muscle. Endothelin-1 and
      the hypoxia-induced transcription factor, Hif2alpha were also highly enriched in
      ductal smooth muscle at embryonic day 13.5 and were dependent on Tfap2beta for
      their expression in this domain. Hif2alpha functioned as a negative regulator of
      Tfap2beta-induced transcription by disrupting protein-DNA interactions,
      suggesting a negative feedback loop regulating Tfap2beta activity. Our data
      indicate that Tfap2beta, Et-1, and Hif2alpha act in a transcriptional network
      during ductal smooth muscle development and that disruption of this pathway may
      contribute to patent ductus arteriosus by affecting the development of smooth
      muscle within the ductus arteriosus.

PMID- 18635824
TI  - Burst emergence of intracellular Ca2+ waves evokes arrhythmogenic oscillatory
      depolarization via the Na+-Ca2+ exchanger: simultaneous confocal recording of
      membrane potential and intracellular Ca2+ in the heart.
AB  - Intracellular Ca(2+) waves (CaWs) of cardiomyocytes are spontaneous events of
      Ca(2+) release from the sarcoplasmic reticulum that are regarded as an important
      substrate for triggered arrhythmias and delayed afterdepolarizations. However,
      little is known regarding whether or how CaWs within the heart actually produce
      arrhythmogenic membrane oscillation because of the lack of data confirming direct
      correlation between CaWs and membrane potentials (V(m)) in the heart. On the
      hypothesis that CaWs evoke arrhythmogenic oscillatory depolarization when they
      emerge synchronously and intensively in the heart, we conducted simultaneous
      fluorescence recording of intracellular Ca(2+) ([Ca(2+)](i)) dynamics and V(m) of
      ventricular myocytes on subepicardial surfaces of Langendorff-perfused rat hearts
      using in situ dual-view, rapid-scanning confocal microscopy. In intact hearts
      loaded with fluo4/acetoxymethyl ester and RH237 under perfusion with cytochalasin
      D at room temperature, individual myocytes exhibited Ca(2+) transients and action
      potentials uniformly on ventricular excitation, whereas low-K(+)-perfused (2.4
      mmol/L) hearts exhibited CaWs sporadically between Ca(2+) transients without
      discernible membrane depolarization. Further [Ca(2+)](i) loading of the heart,
      produced by rapid pacing and addition of isoproterenol, evoked triggered activity
      and subsequent oscillatory V(m), which are caused by burst emergence of CaWs in
      individual myocytes. Such arrhythmogenic membrane oscillation was abolished by
      ryanodine or the Na(+)-Ca(2+) exchanger inhibitor SEA0400, indicating an
      essential role of CaWs and resultant Na(+)-Ca(2+) exchanger-mediated
      depolarization in triggered activity. In summary, we demonstrate a mechanistic
      link between intracellular CaWs and arrhythmogenic oscillatory depolarizations in
      the heart. Our findings provide a cellular perspective on abnormal [Ca(2+)](i)
      handling in the genesis of triggered arrhythmias in the heart.

PMID- 18635825
TI  - G protein-coupled receptor kinase 2 ablation in cardiac myocytes before or after
      myocardial infarction prevents heart failure.
AB  - Myocardial G protein-coupled receptor kinase (GRK)2 is a critical regulator of
      cardiac beta-adrenergic receptor (betaAR) signaling and cardiac function. Its
      upregulation in heart failure may further depress cardiac function and contribute
      to mortality in this syndrome. Preventing GRK2 translocation to activated betaAR
      with a GRK2-derived peptide that binds G(beta)gamma (betaARKct) has benefited
      some models of heart failure, but the precise mechanism is uncertain, because
      GRK2 is still present and betaARKct has other potential effects. We generated
      mice in which cardiac myocyte GRK2 expression was normal during embryonic
      development but was ablated after birth (alphaMHC-Cre x GRK2 fl/fl) or only after
      administration of tamoxifen (alphaMHC-MerCreMer x GRK2 fl/fl) and examined the
      consequences of GRK2 ablation before and after surgical coronary artery ligation
      on cardiac adaptation after myocardial infarction. Absence of GRK2 before
      coronary artery ligation prevented maladaptive postinfarction remodeling and
      preserved betaAR responsiveness. Strikingly, GRK2 ablation initiated 10 days
      after infarction increased survival, enhanced cardiac contractile performance,
      and halted ventricular remodeling. These results demonstrate a specific causal
      role for GRK2 in postinfarction cardiac remodeling and heart failure and support
      therapeutic approaches of targeting GRK2 or restoring betaAR signaling by other
      means to improve outcomes in heart failure.

PMID- 18635826
TI  - Nature versus nurture in cardiac conduction: toward integrative paradigm of
      cardiac tissue engineering.

PMID- 18635827
TI  - Choosing sides in polarized endothelial adaptation to shear stress.

PMID- 18635828
TI  - Mesenchymal stem cell-derived IL-10 and recovery from infarction: a third pitch
      for the chord.

PMID- 18635829
TI  - Therapeutic vasculogenesis: it takes two.

PMID- 18635830
TI  - When HDL gets fat...

PMID- 18635831
TI  - Ordinal reanalysis of the SHEP trial.

PMID- 18635833
TI  - Strengthening the link: the critical role of children in the stroke chain of
      recovery.

PMID- 18635832
TI  - Sleep duration and risk of ischemic stroke in postmenopausal women.
AB  - BACKGROUND AND PURPOSE: Many studies have shown a U-shape association between
      sleep duration and mortality, but epidemiological evidence linking cardiovascular
      diseases with habitual sleep patterns is limited and mixed. METHODS: We conducted
      a prospective study on 93 175 older women (aged 50 to 79 years) in the Women's
      Health Initiative Observational study cohort to examine the risk of ischemic
      stroke in relation to self-reported sleep duration. Cox models were used to
      investigate the putative associations, adjusting for multiple sociodemographic
      and lifestyle factors, depression, snoring, sleepiness symptoms, and other
      cardiovascular disease-related clinical characteristics. RESULTS: At baseline,
      8.3% of subjects had reported their sleep duration as <or=5 hours per night and
      4.6% reported long duration of sleep (>or=9 hours/night). After an average of 7.5
      years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable
      adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of
      7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and
      1.70 (1.32, 2.21) for women reporting <or=6, 8, and >or=9 hours of sleep. A
      modestly stronger association with sleep duration <or=6 hours per night (RR,
      1.22; 1.03, 1.44) was noted among women without prevalent cardiovascular disease
      at baseline. Our analyses also reveal that the adverse effect of long sleep is
      likely independent of the increased risk for ischemic stroke associated with
      frequent snoring and sleepiness (RR, 1.31; 1.00, 1.72). CONCLUSIONS: Habitual
      sleep patterns are important neurobehavioral determinants of risk for ischemic
      stroke in postmenopausal women. The underlying neurobiology and mechanistic
      mediators for the putative adverse effect of long sleep (>or=9 hours/night) need
      further elucidation.

PMID- 18635834
TI  - Identifying low-quality preclinical studies.

PMID- 18635835
TI  - Stroke-induced sudden-autonomic death: areas of fatality beyond the insula.

PMID- 18635836
TI  - Ipsilateral motor-related hyperactivity in patients with cerebral occlusive
      vascular disease.
AB  - BACKGROUND AND PURPOSE: Cerebral occlusive vascular disease is an established
      risk factor for ischemic stroke; however, little is known about its effects on
      brain function in patients without stroke. To detect possible functional
      alterations, we used magnetoencephalography and evaluated cerebral cortical
      activity during hand motor tasks in a group of such patients. Method- Event
      related desynchronization (ERD) during hand-grasping and self-paced finger
      tapping tasks was examined in 38 right-hand-dominant patients with occlusive
      disease of the internal carotid or middle cerebral artery caused by diverse
      pathologies (atherosclerosis, 28; others, 10) and in 8 control subjects. All
      patients had no apparent motor impairments. The spatial distribution and the
      intensity (t value) of ERD in the beta band were analyzed with synthetic aperture
      magnetometry. According to the laterality index calculated from the ratios of
      peak t values on ipsilateral vs contralateral (with respect to the hand movement)
      hemispheres, the distribution of ERD was classified into 3 patterns:
      contralateral, bilateral, and ipsilateral. RESULTS: Abnormal ipsilateral dominant
      distribution of beta ERD was observed significantly more often during
      contralesional hand grasping in patients with atherosclerotic vascular lesion. It
      was accompanied by significantly higher t values on the ipsilateral hemisphere,
      without a decrease in those on the contralateral side. The age, the rating scores
      of periventricular hyperintensity, and ventricular size were all significantly
      higher in patients who showed the ipsilateral-dominant pattern. CONCLUSIONS:
      Abnormal ipsilateral hyperactivity may indicate the presence of subclinical
      functional alterations related to atherosclerotic occlusive vascular disease.

PMID- 18635837
TI  - Curable cause of paraplegia: spinal dural arteriovenous fistulae.
AB  - BACKGROUND AND PURPOSE: The rarity of spinal dural arteriovenous fistulae makes
      physicians often overlook this potential diagnosis in patients with progressive
      gait disturbance and paraparesis. Consequently, patients with spinal dural
      arteriovenous fistulae can gradually become completely paraplegic if the final
      diagnosis is delayed considerably. The objective of the current study is to
      demonstrate that, particularly in patients with paraplegia, surgical treatment of
      fistula is necessary and often has a favorable outcome. METHODS: Of 42 patients
      with spinal dural arteriovenous fistulae treated in our institution (surgery or
      endovascular treatment), 6 were paraplegic preoperatively (Grade IV on the
      McCormick scale and Grade V on the Aminoff scale, Grade 5 of modified Rankin
      Scale with motor ASIA between 0 and 10 for both lower limbs). Their clinical
      history revealed that paraplegia appeared progressively within a period of <3
      months. All patients were clinically evaluated at 6 weeks, 6 months, and then
      annually during an average follow-up of 3 years. Patients received at least one
      spinal angiography and MRI test during the follow-up period. RESULTS: Total
      exclusion of the fistula was performed surgically in all cases and was confirmed
      by spinal angiography. No surgical complications were recorded. All patients
      improved postoperatively. Three patients showed almost normal walking (Grade I on
      the McCormick scale, I on the Aminoff scale, Grade 1 of modified Rankin Scale)
      and 3 were able to walk with a cane (Grade II on McCormick, Grade III on Aminoff
      scale, Grade 2 of modified Rankin Scale). MRI tests were normal in all patients.
      CONCLUSIONS: Our results indicate that treatment of fistula is a necessary
      intervention, even in patients with complete paraplegia.

PMID- 18635838
TI  - MRA/DWI mismatch: a novel concept or something one could get easier and cheaper?

PMID- 18635839
TI  - Cerebral amyloid angiopathy, hemorrhages and superficial siderosis.

PMID- 18635840
TI  - Dural arteriovenous shunts: a new classification of craniospinal epidural venous
      anatomical bases and clinical correlations.
AB  - BACKGROUND AND PURPOSE: The craniospinal epidural spaces can be categorized into
      3 different compartments related to their specific drainage role of the bone and
      central nervous system, the ventral epidural, dorsal epidural, and lateral
      epidural groups. We propose this new classification system for dural
      arteriovenous shunts and compare demographic, angiographic, and clinical
      characteristics of dural arteriovenous shunts that develop in these 3 different
      locations. METHODS: Three hundred consecutive cases (159 females, 141 males; mean
      age: 47 years; range, 0 to 87 years) were reviewed for patient demographics,
      clinical presentation, multiplicity, presence of cortical and spinal venous
      reflux, and outflow restrictions and classified into the 3 mentioned groups.
      RESULTS: The ventral epidural group (n=150) showed a female predominance, more
      benign clinical presentations, lower rate of cortical and spinal venous reflux,
      and no cortical and spinal venous reflux without restriction of the venous
      outflow. The dorsal epidural group (n=67) had a lower mean age and a higher rate
      of multiplicity. The lateral epidural group (n=63) presented later in life with a
      male predominance, more aggressive clinical presentations, and cortical and
      spinal venous reflux without evidence of venous outflow restriction. All
      differences were statistically significant (P<0.001). CONCLUSIONS: Dural
      arteriovenous shunts predictably drain either in pial veins or craniofugally
      depending on the compartment involved by the dural arteriovenous shunt.
      Associated conditions (outflow restrictions, high-flow shunts) may change that
      draining pattern. The significant differences between the groups of the new
      classification support the hypothesis of biological and/or developmental
      differences in each epidural region and suggest that dural arteriovenous shunts
      are a heterogeneous group of diseases.

PMID- 18635841
TI  - Effect of simultaneous botulinum toxin injections into several muscles on
      impairment, activity, participation, and quality of life among stroke patients
      presenting with a stiff knee gait.
AB  - BACKGROUND AND PURPOSE: Walking is an essential activity for daily life and
      social participation, and it is frequently limited after stroke. A lack of knee
      flexion during the swing phase (stiff knee) is one of the impairments that
      restrict walking ability among patients with hemiparetic spasticity. Our purpose
      was to study the effect of Botulinum toxin type A (BoNT A) injections in several
      spastic muscles on the impairment, activity, participation, and quality of life
      of patients with chronic stroke presenting with a stiff knee gait. METHODS:
      Twenty chronic hemiparetic poststroke patients with stiff knee gait and ability
      to walk on a treadmill were recruited. BoNT A was injected into several spastic
      muscles: the rectus femoris (200 U), semitendinosus (100 U) and triceps surae
      (200 U). Patients' neurological impairments (Ashworth scale, Duncan-Ely test,
      Stroke Impairment Assessment Set, and instrumented gait analysis), activity
      (ABILOCO and 10-m walking test), and participation (SATISPART-Stroke and 36-item
      Short-Form Health Survey) were assessed before and 2 months after the injection.
      RESULTS: BoNT A injection reduced the impairments. It improved Stroke Impairment
      Assessment Set (56.5 [48-63] to 56.5 [52.5 to 63]; P<0.001), reduced rectus
      femoris muscle tone (2 [1 to 2.5] to 0 [0 to 1]; P<0.001), and reduced
      semitendinosus muscle tone (1 [1 to 1.5] to 1 [0 to 1]; P<0.001). Gait analysis
      demonstrated increased knee flexion during the swing phase (22+/-19 degrees to
      27+/-16 degrees ; P=0.03), decreased external mechanical work (0.66+/-0.38 to
      0.59+/-0.25 J kg(-1) m(-1); P=0.04), and demonstrated a lower energy cost (5.8+/
      1.9 to 4.9+/-1.9 J kg(-1) m(-1); P=0.03). The patients' locomotion ability was
      improved (2.2+/-1.9 to 3.2+/-2.1 logits; P=0.03). The participation and quality
      of life remained unchanged. CONCLUSIONS: BoNT A injections in several muscles
      improved the stiff knee gait and the locomotion ability in adult stroke patients.

PMID- 18635842
TI  - Evidence for the efficacy of NXY-059 in experimental focal cerebral ischaemia is
      confounded by study quality.
AB  - BACKGROUND AND PURPOSE: The neutral results of the SAINT II trial have again
      highlighted difficulties translating neuroprotective efficacy from bench to
      bedside. Animal studies are susceptible to study quality biases, which may lead
      to overstatement of efficacy. We report the impact of study quality on published
      estimates of the efficacy of NXY-059 in animal models of stroke. METHODS: We
      conducted a systematic review and stratified meta-analysis of published studies
      describing the efficacy of NXY-059 in experimental focal cerebral ischemia.
      RESULTS: Overall, NXY-059 improved infarct volume by 43.3% (95% CI, 34.7 to
      52.8). Only 2 of 9 publications reported randomization, concealment of treatment
      allocation, and blinded outcome assessment. Studies not reporting these quality
      items gave substantially higher estimates of efficacy than did higher-quality
      studies. CONCLUSIONS: The reported efficacy of NXY-059 in animal models of stroke
      is confounded by low study quality. The failure of SAINT II highlights the need
      for substantial improvements in the design, conduct, and reporting of animal
      studies; journals can play an important role in this by adopting standards for
      animal studies similar to those agreed over 10 years ago for clinical trials.

PMID- 18635843
TI  - Protecting against cerebrovascular injury: contributions of 12/15-lipoxygenase to
      edema formation after transient focal ischemia.
AB  - BACKGROUND AND PURPOSE: The concept of the neurovascular unit suggests that
      effects on brain vasculature must be considered if neuroprotection is to be
      achieved in stroke. We previously reported that 12/15-lipoxygenase (12/15-LOX) is
      upregulated in the peri-infarct area after middle cerebral artery occlusion in
      mice, and 12/15-LOX contributes to brain damage after ischemia-reperfusion. The
      current study was designed to investigate 12/15-LOX involvement in vascular
      injury in the ischemic brain. METHODS: In cell culture, a human brain
      microvascular endothelial cell line was subjected to either hypoxia or H(2)O(2)
      induced oxidative stress with or without lipoxygenase inhibitors. For in vivo
      studies, mice were subjected to 90 minutes middle cerebral artery occlusion, and
      the effects of either 12/15-LOX gene knockout or treatment with lipoxygenase
      inhibitors were compared. Expression of 12/15-LOX and claudin-5 as well as
      extravasation of immunoglobulin G were detected by immunohistochemistry. Edema
      was measured as water content of brain hemispheres according to the wet-dry
      weight method. RESULTS: Brain endothelial cells were protected against hypoxia
      and H(2)O(2) by the lipoxygenase inhibitor baicalein. After focal ischemia, 12/15
      LOX was increased in neurons and endothelial cells. The vascular tight junction
      protein claudin-5 underwent extensive degradation in the peri-infarct area, which
      was partially prevented by the lipoxygenase inhibitor baicalein. Leakage of
      immunoglobulin G into the brain parenchyma was significantly reduced in 12/15-LOX
      knockout mice as well as wild-type mice treated with baicalein. Likewise, brain
      edema was significantly ameliorated. CONCLUSIONS: 12/15-LOX may contribute to
      ischemic brain damage not just by causing neuronal cell death, but also by
      detrimental effects on the brain microvasculature. 12/15-LOX inhibitors may thus
      be effective as both neuroprotectants and vasculoprotectants.

PMID- 18635844
TI  - Establishing final infarct volume: stroke lesion evolution past 30 days is
      insignificant.

PMID- 18635845
TI  - Management of stroke in infants and children: a scientific statement from a
      Special Writing Group of the American Heart Association Stroke Council and the
      Council on Cardiovascular Disease in the Young.
AB  - PURPOSE: The purpose of this statement is to review the literature on childhood
      stroke and to provide recommendations for optimal diagnosis and treatment. This
      statement is intended for physicians who are responsible for diagnosing and
      treating infants, children, and adolescents with cerebrovascular disease.
      METHODS: The Writing Group members were appointed by the American Heart
      Association Stroke Council's Scientific Statement Oversight Committee. The panel
      included members with several different areas of expertise. Each of the panel's
      recommendations was weighted by applying the American Heart Association Stroke
      Council's Levels of Evidence grading algorithm. After being reviewed by panel
      members, the manuscript was reviewed by 4 expert peer reviewers and by members of
      the Stroke Council Leadership Committee and was approved by the American Heart
      Association Science Advisory and Coordinating Committee. We anticipate that this
      statement will need to be updated in 4 years. RESULTS: Evidence-based
      recommendations are provided for the prevention of ischemic stroke caused by
      sickle cell disease, moyamoya disease, cervicocephalic arterial dissection, and
      cardiogenic embolism. Recommendations on the evaluation and management of
      hemorrhagic stroke also are provided. Protocols for dosing of heparin and
      warfarin in children are suggested. Also included are recommendations on the
      evaluation and management of perinatal stroke and cerebral sinovenous thrombosis
      in children.

PMID- 18635846
TI  - The stroke impact scale 3.0: evaluation of acceptability, reliability, and
      validity of the Brazilian version.
AB  - BACKGROUND AND PURPOSE: We sought to assess the psychometric attributes of the
      Brazilian version of the Stroke Impact Scale (SIS) 3.0 in stroke survivors.
      METHODS: Patients were evaluated by the National Institutes of Health Stroke
      Scale, Mini-Mental State Examination, Barthel Index, Lawton Instrumental
      Activities of Daily Living Scale, modified Rankin Scale, Geriatric Depression
      Scale, and Hospital Anxiety and Depression Scale. Health-related quality of life
      was evaluated with the MOS-Short Form 36 and SIS 3.0. RESULTS: One hundred
      seventy-four stroke survivors were assessed (mean age, 56.9 years; 55.2% male).
      Hand function had a prominent floor effect (45.9%), whereas a ceiling effect was
      observed in the communication domain (17.3%). The internal consistency of SIS
      (Cronbach's alpha=0.94) and SIS domains (item-dimension correlation, 0.17 to
      0.89) were satisfactory; only the emotion domain had poor internal consistency
      (Cronbach's alpha=0.49). Test-retest reliability was evaluated in 50 consecutive
      patients. Concerning the stability of the SIS, the weighted kappa values ranged
      from 0.33 (item 3a) to 0.94 (item 7e). Intraclass correlation coefficient values
      for the SIS domains ranged from 0.48 (emotion) to 0.94 (hand function). Standard
      error of measurement values for SIS domains ranged from 6.85 (mobility) to 9.63
      (social participation). Regarding convergent validity, a significant correlation
      (Spearman's correlation coefficient, P<0.0001) was found between the SIS
      composite physical domain and the National Institutes of Health Stroke Scale (
      0.69), modified Rankin Scale (-0.81), Barthel Index (0.87), Lawton Scale (0.76),
      and MOS-Short Form 36 physical component summary (0.61). SIS domain scores
      significantly decreased as modified Rankin Scale scores increased (discriminative
      validity; ANOVA, P<0.0001). CONCLUSIONS: The Brazilian version of SIS 3.0 has
      satisfactory psychometric properties and can be used in stroke survivors to
      assess health-related quality of life.

PMID- 18635847
TI  - Low vitamin d levels predict stroke in patients referred to coronary angiography.
AB  - BACKGROUND AND PURPOSE: Vitamin D deficiency is common among the elderly and may
      contribute to cerebrovascular diseases. We aimed to elucidate whether low vitamin
      D levels are predictive for fatal stroke. METHODS: The LUdwigshafen RIsk and
      Cardiovascular Health (LURIC) study includes 3316 patients who were referred to
      coronary angiography at baseline between 1997 and 2000. 25-Hydroxyvitamin D
      [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured in 3299 and 3315
      study participants, respectively. To account for the seasonal variation of
      vitamin D metabolites, we calculated z values for the 25(OH)D and 1,25(OH)2D
      concentrations within each month of blood draw. RESULTS: During a median follow
      up time of 7.75 years, 769 patients died, including 42 fatal (ischemic and
      hemorrhagic) strokes. When compared with survivors in binary logistic-regression
      analyses, the odds ratios (with 95% CIs) for fatal stroke were 0.58 (0.43 to
      0.78; P<0.001) per z value of 25(OH)D and 0.62 (0.47 to 0.81; P<0.001) per z
      value of 1,25(OH)2D. After adjustment for several possible confounders, these
      odds ratios remained significant for 25(OH)D at 0.67 (0.46 to 0.97; P=0.032) and
      for 1,25(OH)2D at 0.72 (0.52 to 0.99; P=0.047). Z values of 25(OH)D and
      1,25(OH)2D were also reduced in the 274 patients who had a history of previous
      cerebrovascular disease events at baseline. CONCLUSIONS: Low levels of 25(OH)D
      and 1,25(OH)2D are independently predictive for fatal strokes, suggesting that
      vitamin D supplementation is a promising approach in the prevention of strokes.

PMID- 18635848
TI  - Cathepsin B, K, and S are expressed in cerebral aneurysms and promote the
      progression of cerebral aneurysms.
AB  - BACKGROUND AND PURPOSE: A cerebral aneurysm (CA) causes catastrophic subarachnoid
      hemorrhage. Degradation of extracellular matrix in arterial walls is a prominent
      feature of cerebral aneurysms. We investigated the expression and role of
      cysteine cathepsins, collagen- and elastin- degrading proteinases, in CA
      progression. METHODS: CAs were induced in Sprague-Dawley rats with or without
      cysteine cathepsin inhibitor, NC-2300. Expression of cathepsin B, K, S, and
      cystatin C, an endogenous inhibitor of cysteine cathepsins, in aneurysmal walls
      was examined in quantitative RT-PCR and immunohistochemistry. The activity of
      cysteine cathepsins and collagenase I and IV in aneurysmal walls was also
      assessed. Finally, expression of cysteine cathepsins and cystatin C in human CAs
      was examined. RESULTS: Quantitative RT-PCR and immunohistochemistry revealed
      upregulated expression of cathepsin B, K, and S in the late stage of aneurysm
      progression. In contrast, cystatin C expression was reduced with aneurysm
      progression. Treatment with NC-2300 resulted in the decreased incidence of
      advanced CAs. The activity of cysteine cathepsins and collagenase I and IV in
      aneurysmal walls was reduced and elastin content was increased in the NC-2300
      treated group. Finally, immunohistochemistry for cysteine cathepsins and cystatin
      C expression in human CAs showed the same expression pattern as in the rat study.
      CONCLUSIONS: Data obtained by using NC-2300 revealed an important role of
      cysteine cathepsins in the progression of CAs. Our findings strongly suggest that
      an imbalance between cysteine cathepsins and their inhibitor may cause the
      excessive breakdown of extracellular matrix in the arterial walls leading to the
      progression and rupture of CAs.

PMID- 18635849
TI  - Progression of cerebral small vessel disease in relation to risk factors and
      cognitive consequences: Rotterdam Scan study.
AB  - BACKGROUND AND PURPOSE: Cerebral white matter lesions and lacunar infarcts are
      small vessel disease-related lesions, which are associated with cognitive decline
      and dementia. We aimed to assess the relationship between risk factors, effect
      modifiers, and progression of these lesions. Furthermore, we studied the
      cognitive consequences of lesion progression. METHODS: Six hundred sixty-eight
      people, aged 60 to 90 years, underwent repeated MRI scanning and
      neuropsychological testing within 3-year follow-up. We rated incident lacunar
      infarcts and change in periventricular and subcortical white matter lesion
      severity with a semiquantitative scale. We assessed the relationships between
      age, sex, baseline lesion load, risk factors, lesion progression, and change in
      cognitive function by multivariate regression analyses and additional stratified
      analyses. RESULTS: Baseline lesion load, higher age, high blood pressure, and
      current smoking were independently associated with progression of white matter
      lesions. Women had more marked progression of subcortical white matter lesions
      and incident lacunar infarcts compared with men. Carotid atherosclerosis was
      associated with incident lacunar infarcts. Higher blood pressure did not
      contribute to lesion progression in people with already severe lesions at
      baseline nor in the very old. Lesion progression was associated with a paralleled
      decline in general cognitive function and in particular with a decreased
      information processing speed. CONCLUSIONS: Higher age, female sex, cigarette
      smoking, elevated blood pressure, and baseline lesion load were associated with
      small vessel disease progression. Age and baseline lesion load influenced the
      risk relations with blood pressure. Progression of small vessel disease was
      related to a paralleled decline in cognitive function.

PMID- 18635850
TI  - Blood cell-derived RANTES mediates cerebral microvascular dysfunction,
      inflammation, and tissue injury after focal ischemia-reperfusion.
AB  - BACKGROUND AND PURPOSE: Although chemokines have been implicated in
      cardiovascular diseases, few studies have addressed the role of these
      inflammatory mediators in ischemic stroke. This study tested the hypothesis that
      RANTES (CCL5; regulated on activation, normal T-cell expressed and secreted)
      mediates the cerebral microvascular dysfunction, inflammation, and tissue injury
      induced by brain ischemia and reperfusion. METHODS: After 60-minute middle
      cerebral artery occlusion and reperfusion, the adhesion of leukocytes and
      platelets in cerebral venules, infarct volume, and blood-brain barrier
      permeability were measured in wild-type mice (WT), RANTES-deficient mice (RANTES(
      /-)), WT mice transplanted with RANTES(-/-) bone marrow (RANTES>WT), and control
      bone marrow chimeras (WT>WT). The concentration of RANTES and several cytokines
      was also measured by enzyme-linked immunosorbent assay and a cytometric bead
      array. RESULTS: The enhanced leukocyte and platelet adhesion, increased blood
      brain barrier permeability, and tissue infarction elicited in WT and WT>WT mice
      after middle cerebral artery occlusion and reperfusion were significantly blunted
      in RANTES(-/-) mice. Similar attenuation of the middle cerebral artery occlusion
      and reperfusion-induced responses were noted in RANTES>WT chimeras. Although
      RANTES deficiency did not alter the changes in tissue cytokine levels elicited by
      middle cerebral artery occlusion and reperfusion, plasma concentrations
      interleukin-6, interleukin-10, and interleukin-12 were all reduced. CONCLUSIONS:
      These findings implicate blood cell-derived RANTES in the microvascular,
      inflammatory, and tissue injury responses of the brain to ischemia and
      reperfusion.

PMID- 18635851
TI  - 'Hip-hop' stroke: a stroke educational program for elementary school children
      living in a high-risk community.
AB  - BACKGROUND AND PURPOSE: Public stroke recognition is poor and poses a barrier to
      acute stroke treatment. We describe a stroke literacy program that teaches
      elementary school children in high-risk communities to recognize stroke and form
      an urgent action plan; we then present results of an intervention study using the
      program. METHODS: "Hip-Hop" Stroke uses culturally and age-appropriate music and
      dance to enhance an interactive didactic curriculum including the FAST mnemonic
      (Facial droop, Arm weakness, Speech disturbance, Time to call 911). The program
      occurred in central Harlem, New York City, a community with high stroke risk.
      During the 2006 to 2007 school year, 582 fourth, fifth, and sixth graders (9 to
      11 years of age) participated in 1-hour sessions over 3 consecutive days. Stroke
      knowledge was tested before and after the program with a 94% group participant
      retention. RESULTS: Students learned and retained knowledge well for stroke
      localization (20% correct before intervention, 93% correct immediately afterward,
      and 86% correct after 3-month delay; P<0.001 both posttests versus baseline), the
      term "brain attack" (16% pretest, 95% immediate, 86% delayed; P<0.001), and to
      call 911 for stroke (78% pretest, 99.8% immediate, 98% delayed; P<0.001). FAST
      stroke symptoms (facial droop and slurred speech) were better retained than non
      FAST symptoms (headache and blurred vision) at 3 months (P<0.001). For stroke
      prevention measures, dietary change and exercise were better learned than
      concepts of diabetes, hypertension, and cholesterol. CONCLUSIONS: Elementary
      school children are educable about stroke, retain their knowledge well, and may
      be able to appropriately activate emergency services for acute stroke.
      Incorporating cultural elements such as hip-hop music may improve retention of
      stroke knowledge among the youth.

PMID- 18635852
TI  - In-hospital stroke treated with intravenous tissue plasminogen activator.
AB  - BACKGROUND AND PURPOSE: In-hospital strokes (IHSs) are potential candidates for
      thrombolysis. We analyzed the treatment procedures, safety, and efficacy of
      intravenous tissue plasminogen activator (IV-tPA) in IHSs compared with out-of
      hospital strokes (OHSs). METHODS: This study was based on a multicenter
      prospective registry of patients treated with IV-tPA divided into IHSs and OHSs.
      We recorded intrahospital delays and stroke outcomes. RESULTS: Among 367 patients
      treated with IV-tPA, 30 were IHSs. Baseline characteristics were similar except
      for a greater proportion of diabetes (36.7% vs 17.5%, P=0.01), cardiac failure
      (16.7% vs 5.3%, P=0.014), and atrial fibrillation (33.3% vs 17.5%, P=0.034) in
      IHSs than OHSs. In-hospital delays were significantly longer in IHSs for door-to
      computed tomography time (39.5+/-18.7 vs 22.6+/-19.7 minutes, P<0.0001) and
      computed tomography-to-treatment time (92.0+/-26.1 vs 65.4+/-25.8 minutes,
      P<0.0001). No differences were observed in safety or efficacy. CONCLUSIONS: In
      hospital procedures for thrombolysis proceed more slowly in IHSs than in OHSs.
      Thrombolysis is safe and efficient in IHS.

PMID- 18635853
TI  - Cerebral venous thrombosis: a descriptive multicenter study of patients in
      Pakistan and Middle East.
AB  - BACKGROUND AND PURPOSE: The natural history, causative factors, and outcomes of
      patients with cerebral venous thrombosis from Asia and Middle East have not been
      well described. This descriptive multicenter study describes the results for
      cerebral venous thrombosis patients in South Asia and the Middle East. METHODS:
      The retrospective and prospective data of patients with radiologically confirmed
      cerebral venous thrombosis were collected from 4 centers located in Pakistan and
      United Arab Emirates. The demographic, clinical, radiological, and outcome data
      were recorded and analyzed. Primary outcome was death or dependency (modified
      Rankin score >2) at the time of hospital discharge. RESULTS: This study included
      109 patients with cerebral venous thrombosis; the presenting features most
      commonly being observed were headache (81%), focal motor deficits (45%), seizures
      (39%), and mental status changes (37%). Important predisposing factors included
      systemic and central nervous system infection (18%), postpartum state (17%),
      hyperhomocystinemia (9%), genetic thrombophilia (5%), and oral contraceptive pill
      use (3%). Ninety-six (67%) patients received therapeutic anticoagulation. Seven
      patients died and 43 had poor outcome at discharge. Focal motor deficits (OR,
      2.93; 95% CI, 1.2-7.5; P=0.018) and hemorrhagic infarctions (OR, 2.81; 95% CI,
      1.04-7.85; P=0.041) were independent predictors of unfavorable outcome at
      discharge. Hemorrhagic infarction was the most significant factor of long-term
      unfavorable outcome (OR, 5.87; 95% CI, 1.49-23.02; P=0.011). CONCLUSIONS:
      Infections and postpartum state were the most common predisposing factors for
      cerebral venous thrombosis in this cohort. Most patients (67%) were treated with
      anticoagulation therapy. Almost 50% of patients were dead or disabled at
      discharge.

PMID- 18635854
TI  - Establishing final infarct volume: stroke lesion evolution past 30 days is
      insignificant.
AB  - BACKGROUND AND PURPOSE: Lesion volume measured on MRI has been used as an
      objective surrogate marker for outcome in clinical trials. However, lesion
      volumes vary over time because of edema and tissue loss. This study aims to
      determine if lesion volumes measured at 30 and 90 days after ictus significantly
      differ. METHODS: We performed a retrospective study of 18 patients who had acute
      (<24 hours) DWI and follow-up fluid-attenuated inversion recovery imaging at 5,
      30, and 90 days. Two expert readers segmented lesions and the mean volumes of
      both reads were used in all statistical analyses. RESULTS: Patient age was 65.8
      (SD, 13.7) years and median NIHSS at baseline was 11.5. Inter-rater variability
      for lesion volume measurements was 3.7 (5.8) mL. Acute DWI volume was 19.3 (17.3)
      mL. Fluid-attenuated inversion recovery volumes for 5, 30, and 90 days were 34.3
      (23.5), 18.6 (14.0), and 15.9 (13.8) mL, respectively. These volumes differed
      significantly (P<0.001). Linear regression revealed a strong correlation (r=0.96;
      P<0.001) between lesion volumes at 30 and 90 days with a slope that did not vary
      significantly from 1.0 (P=0.448). CONCLUSIONS: Lesions continue to evolve between
      5 and 90 days, but by 30 days lesion volume approaches final infarct volume.
      While clinical response is the most meaningful outcome measure, our findings
      suggest that lesion volumes measured at 30 days may provide a sufficient
      approximation for final infarct volume for use in early phase clinical trials.

PMID- 18635855
TI  - Dietary calcium intake and risks of stroke, its subtypes, and coronary heart
      disease in Japanese: the JPHC Study Cohort I.
AB  - BACKGROUND AND PURPOSE: Although it has been hypothesized that a high intake of
      dietary calcium may reduce the risk of cardiovascular disease (CVD), no
      prospective studies have been conducted to examine the specific association
      between calcium intake and incidence of stroke or coronary heart disease among
      Japanese with a low average calcium intake. METHODS: To investigate the
      association between calcium intake and risk of CVD, a total of 41 526 Japanese
      men and women age 40 to 59 years without a history of CVD or cancer and who had
      completed a food consumption frequency questionnaire were enrolled in this study.
      The subjects were followed up from 1990 to 1992 to 2003, and after 533 692 person
      years of follow-up, 1321 incident cases of stroke (664 ischemic, 425
      intraparenchymal hemorrhage, and 217 subarachnoid hemorrhage) and 322 of coronary
      heart disease were documented. RESULTS: Total calcium intake showed an inverse
      association with the risk of total stroke; the multivariable hazard ratio and 95%
      CIs for the highest versus the lowest quintile were 0.70 (95% CI, 0.56 to 0.88; P
      for trend=0.02). Dairy calcium intake was inversely associated with risks of
      total and ischemic stroke with respective multivariable hazard ratios (95% CIs)
      of 0.69 (0.56 to 0.85; P for trend=0.007) and 0.69 (0.52 to 0.93; P for
      trend=0.05). Dietary calcium intake was not significantly associated with risk of
      coronary heart disease. CONCLUSIONS: Dietary calcium intake, especially calcium
      from dairy products, was found to be associated with a reduced incidence of
      stroke among middle-aged Japanese.

PMID- 18635856
TI  - Reliability of clinical diagnosis of the symptomatic vascular territory in
      patients with recent transient ischemic attack or minor stroke.
AB  - BACKGROUND AND PURPOSE: Knowledge of the vascular territory of a recent transient
      ischemic attack or minor stroke determines appropriate investigations and the
      need for territory-specific interventions such as endarterectomy and stenting.
      However, there are few published data on the accuracy of clinical assessment of
      the vascular territory. METHODS: We studied agreement of clinical diagnosis of
      vascular territory in consecutive patients with transient ischemic attack or
      minor stroke with diffusion-weighted MRI who had an acute ischemic lesion(s) in a
      single vascular territory (determined by a neuroradiologist). Three independent
      neurologists (one had seen the patients, the others had a clinical summary)
      diagnosed the most likely vascular territory (carotid or vertebrobasilar) for
      each patient blind to brain imaging. RESULTS: One hundred thirty-three (28.0%) of
      476 patients had a high signal lesion on diffusion-weighted imaging of whom 115
      (86.5%) had a minor stroke and 18 (13.5%) a transient ischemic attack.
      Interobserver agreement (kappa statistic) on the territory ranged from 0.46 to
      0.60. The agreement with diffusion-weighted imaging was only moderate (observer
      1: kappa=0.54, 95% CI=0.36 to 0.72; observer 2: 0.48, 0.31 to 0.64; observer 3:
      0.48, 0.28 to 0.67). Only the presence of visual symptoms improved the accuracy
      of the vascular territory diagnosis (range of kappa: 0.63 to 0.77) but not the
      presence of motor, speech, or sensory symptoms. Sensitivity and specificity for
      the diagnosis of vertebrobasilar territory ranged between 54.2% and 70.8% and
      84.4% to 91.7%, respectively. CONCLUSIONS: The reliability of clinical diagnosis
      of the vascular territory is only moderate, highlighting the importance of
      sensitive brain imaging after transient ischemic attack or minor stroke. Further
      imaging-based research is required to determine the optimal clinical diagnostic
      criteria for classification of the vascular territory.

PMID- 18635857
TI  - Functional integration of newly generated neurons into striatum after cerebral
      ischemia in the adult rat brain.
AB  - BACKGROUND AND PURPOSE: Ischemic injury can induce neurogenesis in the striatum.
      Those newborn neurons can express glutamic acid decarboxylase and choline
      acetyltransferase, markers of GABAergic and cholinergic neurons, respectively.
      The present study investigated whether these GABAergic and cholinergic new
      neurons could differentiate into functional cells. METHODS: Retrovirus containing
      the EGFP gene was used to label dividing cells in striatal slices prepared from
      adult rat brains after middle cerebral artery occlusion. EGFP-targeted
      immunostaining and immunoelectron microscopy were performed to detect whether
      newborn neurons could anatomically form neuronal polarity and synapses with pre
      existent neurons. Patch clamp recording on acute striatal slices of brains at 6
      to 8 weeks after middle cerebral artery occlusion was used to determine whether
      the newborn neurons could display functional electrophysiological properties.
      RESULTS: EGFP-expressing (EGFP(+)) signals could be detected mainly in the cell
      body in the first 2 weeks. From the fourth to thirteenth weeks after their birth,
      EGFP(+) neurons gradually formed neuronal polarity and showed a time-dependent
      increase in dendrite length and branch formation. EGFP(+) cells were copositive
      for NeuN and glutamic acid decarboxylase (EGFP(+)-NeuN(+)-GAD(67)(+)), MAP-2, and
      choline acetyltransferase (EGFP(+)-MAP-2(+)-ChAT(+)). They also expressed
      phosphorylated synapsin I (EGFP(+)-p-SYN(+)) and showed typical synaptic
      structures comprising dendrites and spines. Both GABAergic and cholinergic
      newborn neurons could fire action potentials and received excitatory and
      inhibitory synaptic inputs because they displayed spontaneous postsynaptic
      currents in picrotoxin- and CNQX-inhibited manners. CONCLUSIONS: Ischemia-induced
      newly formed striatal GABAergic and cholinergic neurons could become functionally
      integrated into neural networks in the brain of adult rats after stroke.

PMID- 18635858
TI  - Superficial siderosis: a potential diagnostic marker of cerebral amyloid
      angiopathy in Alzheimer disease.
AB  - BACKGROUND AND PURPOSE: Superficial siderosis of the central nervous system
      results from chronic bleeding in the superficial layers of the cortex and spinal
      cord. In cerebral amyloid angiopathy (CAA), there is amyloid deposition in
      meningeal and meningo-cortical arteries and capillaries, predisposing them to
      rupture. CAA is frequently associated with Alzheimer disease (AD). METHODS: We
      report a series of 3 AD patients with MRI evidence of superficial siderosis. Two
      had neuropathological examination confirming superficial siderosis, AD, and CAA.
      CONCLUSIONS: Superficial siderosis should be recognized within the spectrum of AD
      with CAA and considered as a possible antemortem diagnostic feature.

PMID- 18635859
TI  - In vivo imaging of the inflammatory receptor CD40 after cerebral ischemia using a
      fluorescent antibody.
AB  - BACKGROUND AND PURPOSE: Brain inflammation is a hallmark of stroke, where it has
      been implicated in tissue damage as well as in repair. Imaging technologies that
      specifically visualize these processes are highly desirable. In this study, we
      explored whether the inflammatory receptor CD40 can be noninvasively and
      specifically visualized in mice after cerebral ischemia using a fluorescent
      monoclonal antibody, which we labeled with the near-infrared fluorescence dye
      Cy5.5 (Cy5.5-CD40MAb). METHODS: Wild-type and CD40-deficient mice were subjected
      to transient middle cerebral artery occlusion. Mice were either intravenously
      injected with Cy5.5-CD40MAb or control Cy5.5-IgGMAb. Noninvasive and ex vivo near
      infrared fluorescence imaging was performed after injection of the compounds.
      Probe distribution and specificity was further assessed with single-plane
      illumination microscopy, immunohistochemistry, and confocal microscopy. RESULTS:
      Significantly higher fluorescence intensities over the stroke-affected
      hemisphere, compared to the contralateral side, were only detected noninvasively
      in wild-type mice that received Cy5.5-CD40MAb, but not in CD40-deficient mice
      injected with Cy5.5-CD40MAb or in wild-type mice that were injected with Cy5.5
      IgGMAb. Ex vivo near-infrared fluorescence showed an intense fluorescence within
      the ischemic territory only in wild-type mice injected with Cy5.5-CD40MAb. In the
      brains of these mice, single-plane illumination microscopy demonstrated vascular
      and parenchymal distribution, and confocal microscopy revealed a partial
      colocalization of parenchymal fluorescence from the injected Cy5.5-CD40MAb with
      activated microglia and blood-derived cells in the ischemic region. CONCLUSIONS:
      The study demonstrates that a CD40-targeted fluorescent antibody enables specific
      noninvasive detection of the inflammatory receptor CD40 after cerebral ischemia
      using optical techniques.

PMID- 18635860
TI  - Racial/Ethnic differences in ischemic stroke rates and the efficacy of warfarin
      among patients with atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Warfarin reduces stroke risk in studies of predominantly
      white patients with atrial fibrillation (AF). Whether nonwhites also have lower
      rates of stroke while treated with warfarin is unclear. METHODS: A multiethnic
      stroke-free cohort hospitalized with nonrheumatic AF was identified in a large
      health maintenance organization. Stroke risk factors (advanced age, diabetes,
      hypertension, and heart failure), warfarin use, and anticoagulation intensity
      were assessed. Crude ischemic stroke rates were calculated by Poisson regression
      for each group while using and not using warfarin. Cox proportional hazard models
      were constructed to assess the independent effect of race/ethnicity on ischemic
      stroke. RESULTS: Between 1995 and 2000, we identified 18867 AF hospitalizations
      (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian). Over the course of 63204
      person-years follow-up (median, 3.3 years), 1226 ischemic strokes were
      identified. The percent-time on warfarin did not differ by race/ethnicity. The
      median percent-time on warfarin that international normalized ratio was 2 to 3
      was 54.5% overall, but it was lower in blacks at 47.8%, whereas the other groups
      had a rate of approximately 54%. The rate ratios (95% CI) of ischemic stroke with
      warfarin compared to without warfarin for whites, blacks, Hispanics, and Asians
      were 0.79 (0.68 to 0.90), 0.92 (0.65 to 1.30), 0.71 (0.48 to 1.05), and 0.65
      (0.34 to 1.23), respectively. CONCLUSIONS: In this cohort, we did not observe a
      statistically significant lower rate of stroke with warfarin therapy among
      nonwhites (in particular blacks) with previous AF hospitalizations. The
      relatively small numbers of nonwhites renders our estimates less than precise and
      should be interpreted with caution.

PMID- 18635861
TI  - The MRA-DWI mismatch identifies patients with stroke who are likely to benefit
      from reperfusion.
AB  - BACKGROUND AND PURPOSE: The aim of this exploratory analysis was to evaluate if a
      combination of MR angiography (MRA) and diffusion-weighted imaging (DWI)
      selection criteria can be used to identify patients with acute stroke who are
      likely to benefit from early reperfusion. METHODS: Data from DEFUSE, a study of
      74 patients with stroke who received intravenous tissue plasminogen activator in
      the 3- to 6-hour time window and underwent MRIs before and approximately 4 hours
      after treatment were analyzed. The MRA-DWI mismatch model was defined as (1) a
      DWI lesion volume less than 25 mL in patients with a proximal vessel occlusion;
      or (2) a DWI lesion volume less than 15 mL in patients with proximal vessel
      stenosis or an abnormal finding of a distal vessel. Favorable clinical response
      was defined as an improvement on the National Institutes of Health Stroke Scale
      score of at least 8 points between baseline and 30 days or a National Institutes
      of Health Stroke Scale score </=1 at 30 days. RESULTS: Twenty-seven of 62
      patients (44%) had an MRA-DWI mismatch. There was a differential response to
      early reperfusion based on MRA-DWI mismatch status. Reperfusion was associated
      with an increased rate of a favorable clinical response in patients with an MRA
      DWI mismatch (OR, 12.5; 95% CI, 1.8 to 83.9) and a lower rate in patients without
      mismatch (OR, 0.2; 95% CI, 0.0 to 0.8). CONCLUSIONS: The MRA-DWI mismatch model
      appears to identify patients with stroke who are likely to benefit from
      reperfusion therapy administered in the 3- to 6-hour time window after symptom
      onset. The criteria established for the MRA-DWI mismatch model in this study
      require validation in an independent cohort.

PMID- 18635862
TI  - Temporal MRI assessment of intracerebral hemorrhage in rats.
AB  - BACKGROUND AND PURPOSE: MRI was used to evaluate the effects of experimental
      intracerebral hemorrhage (ICH) on brain tissue injury and recovery. METHODS:
      Primary ICH was induced in rats (n=6) by direct infusion of autologous blood into
      the striatum. The evolution of ICH damage was assessed by MRI estimates of T(2)
      and T(1sat) relaxation times, cerebral blood flow, vascular permeability, and
      susceptibility-weighted imaging before surgery (baseline) and at 2 hours and 1,
      7, and 14 days post-ICH. Behavioral testing was done before and at 1, 7, and 14
      days post-ICH. Animals were euthanized for histology at 14 days. RESULTS: The MRI
      appearance of the hemorrhage and surrounding regions changed in a consistent
      manner over time. Two primary regions of interest were identified based on T(2)
      values. These included a core, corresponding to the bulk of the hemorrhage, and
      an adjacent rim; both varied with time. The core was associated with
      significantly lower cerebral blood flow values at all post-ICH time points,
      whereas cerebral blood flow varied in the rim. Increases in vascular permeability
      were noted at 1, 7, and 14 days. Changes in T(1sat) were similar to those of
      T(2). MRI and histological estimates of tissue loss were well correlated and
      showed approximately 9% hemispheric tissue loss. CONCLUSIONS: Although the
      cerebral blood flow changes observed with this ICH model may not exactly mimic
      the clinical situation, our results suggest that the evolution of ICH injury can
      be accurately characterized with MRI. These methods may be useful to evaluate
      therapeutic interventions after experimental ICH and eventually in humans.

PMID- 18635864
TI  - Optimizing stroke systems of care by enhancing transitions across care
      environments.
AB  - Stroke affects many aspects of the lives of stroke survivors and their family
      caregivers. Supporting long-term recovery and rehabilitation are necessary to
      help stroke survivors adapt to living with the effects of stroke and to help
      family members adapt to the caregiving role. During recovery and rehabilitation,
      many elements of the health care continuum are utilized, including emergency
      response, acute care, inpatient and outpatient rehabilitation, and community and
      long-term care. With the advent of thrombolytic therapy and the benefits of
      stroke units, stroke survival and outcomes are improving. As a result, the
      current emphasis of stroke system improvement is to implement stroke units
      throughout the developed world. To enhance the patient centeredness of stroke
      care delivery, an important next phase of stroke system improvement will center
      on the experiences of stroke survivors and their family caregivers as they move
      through diverse care environments. The objective of this article was to conduct a
      scoping review of the literature on stroke transitions to identify the current
      areas of research emphasis. This article highlights stroke survivors' and family
      caregivers' experiences with transitions across care environment and some
      potential strategies to improve those transitions.

PMID- 18635863
TI  - Stroke location and association with fatal cardiac outcomes: Northern Manhattan
      Study (NOMAS).
AB  - BACKGROUND AND PURPOSE: Cardiac mortality after stroke is common, and small
      studies have suggested an association of short-term cardiac mortality with
      insular location of cerebral infarction. Few population-based studies with long
      term follow-up have evaluated the effect of stroke location on the long-term risk
      of cardiac death or myocardial infarction (MI) after first ischemic stroke. We
      sought to determine the association between stroke location and cardiac death or
      MI in a multiethnic community-based cohort. METHODS: The Northern Manhattan Study
      is a population-based study designed to determine stroke incidence, risk factors,
      and prognosis in a multiethnic urban population. First ischemic stroke patients
      age 40 or older were prospectively followed up for cardiac death defined as fatal
      MI, fatal congestive heart failure, or sudden death/arrhythmia and for nonfatal
      MI. Primary brain anatomic site was determined by consensus of research
      neurologists. Hazard ratios (HRs) and 95% CIs were calculated by Cox proportional
      hazards models and adjusted for vascular risk factors (age, sex, history of
      coronary disease, hypertension, diabetes, cholesterol, and smoking), stroke
      severity, infarct size, and stroke etiology. RESULTS: The study population
      consisted of 655 patients whose mean age was 69.7+/-12.7 years; 44.6% were men
      and 51.3% were Hispanic. During a median follow-up of 4.0 years, 44 patients
      (6.7%) had fatal cardiac events. Of these, fatal MI occurred in 38.6%, fatal
      congestive heart failure in 18.2%, and sudden death in 43.2%. In multivariate
      models, clinical diagnosis of left parietal lobe infarction was associated with
      cardiac death (adjusted HR=4.45; 95% CI, 1.83 to 10.83) and cardiac death or MI
      (adjusted HR=3.30; 95% CI, 1.45 to 7.51). When analysis of anatomic location was
      restricted to neuroimaging (computed tomography, magnetic resonance imaging, or
      both [n=447]), left parietal lobe infarction was associated with cardiac death
      (adjusted HR=3.37; 95% CI, 1.26 to 8.97), and both left (adjusted HR=3.49; 95%
      CI, 1.38 to 8.80) and right (adjusted HR=3.13; 95% CI, 1.04 to 9.45) parietal
      lobe infarctions were associated with cardiac death or MI. We did not find an
      association between frontal, temporal, or insular stroke and fatal cardiac
      events, although the number of purely insular strokes was small. CONCLUSIONS:
      Parietal lobe infarction is an independent predictor of long-term cardiac death
      or MI in this population. Further studies are needed to confirm whether parietal
      lobe infarction is an independent predictor of cardiac events and death.
      Surveillance for cardiac disease and implementation of cardioprotective therapies
      may reduce cardiac mortality in patients with parietal stroke.

PMID- 18635865
TI  - Migration of neurotrophic factors-secreting mesenchymal stem cells toward a
      quinolinic acid lesion as viewed by magnetic resonance imaging.
AB  - Stem cell-based treatment is a promising frontier for neurodegenerative diseases.
      We propose a novel protocol for inducing the differentiation of rat mesenchymal
      stem cells (MSCs) toward neurotrophic factor (NTF)-secreting cells as a possible
      neuroprotective agent. One of the major caveats of stem cell transplantation is
      their fate post-transplantation. To test the viability of the cells, we tracked
      the transplanted cells in vivo by magnetic resonance imaging (MRI) scans and
      validated the results by histology. MSCs went through a two-step medium-based
      differentiation protocol, followed by in vitro characterization using
      immunocytochemistry and immunoblotting analysis of the cell media. We examined
      the migratory properties of the cells in the quinolinic acid (QA)-induced
      striatal lesion model for Huntington's disease. The induced cells were labeled
      and transplanted posterior to the lesion. Rats underwent serial MRI scans to
      detect cell migration in vivo. On the 19th day, animals were sacrificed, and
      their brains were removed for immunostaining. Rat MSCs postinduction exhibited
      both neuronal and astrocyte markers, as well as production and secretion of NTFs.
      High-resolution two-dimensional and three-dimensional magnetic resonance images
      revealed that the cells migrated along a distinct route toward the lesion. The in
      vivo MRI results were validated by the histological study, which demonstrated
      that phagocytosis had only partially occurred and that MRI could correctly depict
      the status of the migrating cells. The results show that these cells migrated
      toward a QA lesion and therefore survived for 19 days post-transplantation. This
      gives hope for future research harnessing these cells for treating
      neurodegenerative diseases. Disclosure of potential conflicts of interest is
      found at the end of this article.

PMID- 18635866
TI  - Directed evolution of motor neurons from genetically engineered neural
      precursors.
AB  - Stem cell-based therapies hold therapeutic promise for degenerative motor neuron
      diseases, such as amyotrophic lateral sclerosis, and for spinal cord injury.
      Fetal neural progenitors present less risk of tumor formation than embryonic stem
      cells but inefficiently differentiate into motor neurons, in line with their low
      expression of motor neuron-specific transcription factors and poor response to
      soluble external factors. To overcome this limitation, we genetically engineered
      fetal rat spinal cord neurospheres to express the transcription factors HB9,
      Nkx6.1, and Neurogenin2. Enforced expression of the three factors rendered neural
      precursors responsive to Sonic hedgehog and retinoic acid and directed their
      differentiation into cholinergic motor neurons that projected axons and formed
      contacts with cocultured myotubes. When transplanted in the injured adult rat
      spinal cord, a model of acute motor neuron degeneration, the engineered
      precursors transiently proliferated, colonized the ventral horn, expressed motor
      neuron-specific differentiation markers, and projected cholinergic axons in the
      ventral root. We conclude that genetic engineering can drive the differentiation
      of fetal neural precursors into motor neurons that efficiently engraft in the
      spinal cord. The strategy thus holds promise for cell replacement in motor neuron
      and related diseases. Disclosure of potential conflicts of interest is found at
      the end of this article.

PMID- 18635867
TI  - Reprogramming of neural progenitor cells into induced pluripotent stem cells in
      the absence of exogenous Sox2 expression.
AB  - Expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc in mesodermal
      and endodermal derivatives, including fibroblasts, lymphocytes, liver, stomach,
      and beta cells, generates induced pluripotent stem (iPS) cells. It remains
      unknown, however, whether cell types of the ectodermal lineage are equally
      amenable to reprogramming into iPS cells by the same combination of factors. To
      test this, we have isolated genetically marked neural progenitor cells (NPCs)
      from neonatal mouse brains and infected them with viral vectors expressing Oct4,
      Sox2, Klf4, and c-Myc. Infected NPCs gave rise to iPS cells that expressed
      markers of embryonic stem cells, showed demethylation of pluripotency genes,
      formed teratomas, and contributed to viable chimeras. In contrast to other
      somatic cell types, NPCs expressed high levels of endogenous Sox2 and thus did
      not require viral Sox2 expression for reprogramming into iPS cells. Our data show
      that in addition to mesoderm- and endoderm-derived cell types, neural progenitor
      cells of the ectodermal lineage can be reprogrammed into iPS cells, suggesting
      that in vitro reprogramming is a universal process. These results also imply that
      the combination of factors necessary for reprogramming is dependent on cellular
      context. Disclosure of potential conflicts of interest is found at the end of
      this article.

PMID- 18635868
TI  - Stem cell-derived therapeutic myelin repair requires 7% cell replacement.
AB  - Embryonic stem cells (ESCs) hold great potential for therapeutic regeneration and
      repair in many diseases. However, many challenges remain before this can be
      translated into effective therapy. A principal and significant limit for outcome
      evaluations of clinical trials is to define the minimal graft population
      necessary for functional repair. Here we used a preclinical model for
      quantitative analysis of stem cell grafts, with wild-type ESC grafted into myelin
      mutant shiverer hosts, to determine minimum graft levels for therapeutic benefit.
      Using a timed motor function test we identified three groups, including
      recipients indistinguishable from nongrafted shiverer controls (time [t] = 20.1
      +/- 1.1 seconds), mice with marginal improvement (t = 15.7 +/- 1 seconds), and
      mice with substantial phenotype rescue (t = 5.7 +/- 0.9 seconds). The motor
      function rescued chimeras also had a considerably extended life span (T(50) > 128
      days) relative to both shiverer (T(50) = 108 days) and the nonrescued chimeras.
      Retrospective genotype analysis identified a strong correlation (r(2) = 0.85)
      between motor function and ESC-derived chimerism, with > 7% chimerism required
      for rescue in this murine model of central nervous system myelin pathology. These
      results establish the minimal levels of engraftment to anticipate therapeutic
      repair of a cell-autonomous defect by cell transplant therapy.

PMID- 18635869
TI  - Adult germ line stem cells as a source of functional neurons and glia.
AB  - The derivation of autologous pluripotent cells has become a central goal in
      translational stem cell research. Although somatic cell nuclear transfer and
      transcription factor-based reprogramming enable the generation of pluripotent
      cells from adult tissue, both methodologies depend on complex epigenetic
      alterations. Recent data suggest that the adult germ line may represent an
      alternative and natural source of pluripotent stem cells. Multipotent adult germ
      line stem cells (maGSCs) with properties similar to those of embryonic stem cells
      have been derived from mouse spermatogonial stem cells. These cells exhibit
      extensive self-renewal, expression of pluripotency markers, and differentiation
      into derivatives of all three germ layers. Here we report the derivation of
      multipotent neural and glial precursors as well as adherently proliferating
      neural stem cells from maGSCs. Characterization of maGSC-derived neurons revealed
      segregation into GABAergic, glutamatergic, serotonergic, and tyrosine hydroxylase
      positive phenotypes. On a functional level, maGSC-derived neurons generate
      spontaneously active functional networks, which use both glutamatergic and
      GABAergic synaptic transmission and engage in synchronized oscillatory activity.
      maGSC-derived oligodendrocytes undergo full maturation and ensheathe host axons
      in myelin-deficient tissue. Our data suggest that neural stem and precursor cells
      derived from maGSCs could provide a versatile and potentially autologous source
      of functional neurons and glia.

PMID- 18635870
TI  - Mesenchymal stem cells alter migratory property of T and dendritic cells to delay
      the development of murine lethal acute graft-versus-host disease.
AB  - Due to the potent immunoregulatory capacity, mesenchymal stem cells (MSCs) have
      been used in clinical trials to treat acute graft-versus-host disease (aGvHD),
      although the detailed in vivo mechanisms remain elusive. In a murine lethal aGvHD
      model, MSCs delayed the development of the disease. Interestingly, we found that
      MSC infusion increased the number of T lymphocytes in the secondary lymphoid
      organs (SLOs). Since the expression of CD62L and CCR7 is prerequisite for
      lymphocyte migration into SLOs, the in vitro experiments revealed that in the
      presence of MSCs, T lymphocytes (including CD4(+)CD25(+) regulatory T cells)
      preferred to take the naive-like phenotype (CD62L(+)/CCR7(+)) in mixed lymphocyte
      reaction and maintained the migratory activity elicited by secondary lymphoid
      tissue chemokine (SLC). Dendritic cells (DCs) are the initiator of immune
      response. CCR7 expression is pivotal for their maturation and migration into
      SLOs. However, CCR7 expression and SLC-driven migratory activity of DCs were
      remarkably suppressed by MSC coculture. The processes above were realized mainly
      through secretory mechanism. Consistently, MSC infusion maintained T lymphocytes
      to take CD62L(+)/CCR7(+) phenotype and decreased the CCR7 expression and
      proportion of DCs in SLOs of aGvHD mice. In conclusion, the altered migratory
      properties of T cells and DCs might contribute to the immunosuppressive activity
      of transplanted MSCs in the setting of aGvHD. Disclosure of potential conflicts
      of interest is found at the end of this article.

PMID- 18635871
TI  - Effect of inflammatory cytokines on major histocompatibility complex expression
      and differentiation of human neural stem/progenitor cells.
AB  - To develop transplantation of neural stem/progenitor cells (NSPCs) as a
      successful treatment of neurodegenerative disorders, the possible induction of an
      inflammatory response following implantation needs to be taken into
      consideration. Inflammatory cytokines can upregulate major histocompatibility
      complex (MHC) expression on transplanted cells, thereby rendering them more
      susceptible to graft rejection. Furthermore, cytokines also have a profound
      effect on cell differentiation, migration, and proliferation, which can greatly
      affect the outcome of transplantation. Here we studied the effect of three
      inflammatory cytokines, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha
      (TNF-alpha), and interleukin-6 (IL-6), from three different species (human,
      monkey, rat) on expression of MHC molecules and differentiation of two human NSPC
      lines derived from striatum and hippocampus. Human and monkey IFN-gamma strongly
      upregulate MHC expression in both NSPC lines in a dose-dependent manner, whereas
      rat IFN-gamma has an effect on MHC expression only in hippocampal cells.
      Furthermore, TNF-alpha, but not IL-6, upregulates MHC expression in both NSPC
      lines. Differentiation of NSPCs in the presence of cytokines showed that IFN
      gamma increased the neuronal yield threefold in striatal NSPC cultures and
      increased the number of oligodendrocytes twofold in hippocampal NSPC cultures.
      Addition of TNF-alpha enhanced gliogenesis in both cell lines, whereas IL-6
      stimulated neurogenesis. Human NSPC lines' response to cytokines is therefore
      species specific and also dependent on the NSPCs' region of origin. The
      successful translation of different cell lines from animal models to clinical
      trials could be substantially influenced by the species-specific regulation of
      MHC and differentiation as reported here. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 18635872
TI  - The best medicine: exercise training normalizes chemosensitivity and
      sympathoexcitation in heart failure.

PMID- 18635873
TI  - TNF promoter polymorphisms associated with muscle phenotypes in humans.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent catabolic factor to skeletal
      muscle. Single-nucleotide polymorphisms (SNPs) in the promoter region of the TNF
      alpha coding gene, TNF, have been implicated in the interindividual variation in
      TNF-alpha production via transcriptional regulation. The present study
      investigated the association of muscle phenotypes with five TNF promoter SNPs,
      which potentially have biological significance. Female and male volunteers (n =
      1,050) from the Baltimore Longitudinal Study of Aging were genotyped, and their
      regional and total body muscle mass, and arm and leg muscle strength were
      measured. Results indicated that putative high-expression alleles at positions 
      1031 and -863, individually or in combination in the haplotype 1031C-863A-857C
      308G-238G, were associated with lower muscle mass in men. Specifically, carriers
      of -1031C, compared with noncarriers, exhibited lower arm muscle mass (6.4 +/-
      0.1 vs. 6.8 +/- 0.1 kg, P = 0.01) and appendicular skeletal muscle mass (ASM)
      (24.3 +/- 0.4 vs. 25.4 +/- 0.2 kg, P = 0.02), with leg muscle mass and the ASM
      index (ASMI; kg/m(2)) also tending to be lower (P = 0.06 and 0.07). Similarly, 
      863A allele carriers (linked with -1031), compared with noncarriers, exhibited
      lower arm muscle mass (6.4 +/- 0.1 vs. 6.8 +/- 0.1 kg, P = 0.04). Carriers of the
      haplotype 1031C-863A-857C-308G-238G, compared with noncarriers, exhibited lower
      arm muscle mass (6.3 +/- 0.2 vs. 6.8 +/- 0.1 kg, P < 0.01), trunk muscle mass
      (25.7 +/- 0.5 vs. 26.9 +/- 0.3 kg, P < 0.05), and ASM (24.1 +/- 0.5 vs. 25.3 +/-
      0.2 kg, P < 0.025), with tendencies for lower leg muscle mass and ASMI (P = 0.07
      and 0.08). Results indicate that genetic variation in the TNF locus may
      contribute to the interindividual variation in muscle phenotypes in men.

PMID- 18635874
TI  - Comparing the performance of three generations of ActiGraph accelerometers.
AB  - ActiGraph accelerometers are a useful tool for objective assessment of physical
      activity in clinical and epidemiological studies. Several generations of
      ActiGraph are being used; however, little work has been done to verify that
      measurements are consistent across generations. This study employed mechanical
      oscillations to characterize the dynamic response and intermonitor variability of
      three generations of ActiGraph monitors, from the oldest 7164 (n = 13), 71256 (n
      = 12), to the newest GT1M (n = 12). The response due to independent radius (22.1
      60.4 mm) and frequency (25-250 rpm) changes were measured, as well as
      intermonitor variability within each generation. The 7164 and 71256 have similar
      relationships between activity counts and radius (P = 0.229) but were
      significantly different from the GT1M (P < 0.001). The frequency responses were
      nonlinear in all three generations. Although the response curve shapes were
      similar, the differences between generations at various frequencies were
      significant (P < 0.017), especially in the extremes of the measurement range.
      Intermonitor variability was markedly reduced in the GT1M compared with the 7164
      and 71256. Other measurement differences between generations include decreased
      peak counts and decreased sensitivity in low-frequency detection in the GT1M. The
      results of this study revealed an improvement of the intermonitor variability by
      the GT1M monitor. However, the reduced sensitivity in low-count ranges in the
      GT1M may not be well suited for monitoring sedentary or light-intensity
      movements. Furthermore, the algorithms for energy expenditure predictions
      developed using older 7164 monitors may need to be modified for the GT1M.

PMID- 18635875
TI  - Limb venous tone and responsiveness in hypertensive humans.
AB  - Hypertensive (HTN) animal models demonstrate lower venous compliance as well as
      increased venous tone and responsiveness compared with normotensive (NTN)
      controls. However, the extent to which findings in experimental animals can be
      extended to humans is unknown. Forearm and calf venous compliance were quantified
      in 9 NTN (23 +/- 1 yr) and 9 HTN (24 +/- 1 yr) men at baseline, after
      administration of nitroglycerin (NTG), during a cold pressor test (CP), and post
      handgrip exercise ischemia (PEI). Individual pressure-volume relationships from a
      cuff deflation protocol (1 mmHg/s) were modeled with a quadratic regression.
      Regression parameters beta(1) and beta(2) were used to calculate compliance. A
      one-way ANOVA was used to compare the beta parameters and a repeated-measures
      ANOVA was used to compare volumes across all pressures (between groups at
      baseline and within groups during perturbations). Limb venous compliance was
      similar between groups (forearm: NTN beta(1) = 0.11 +/- 0.01 and beta(2) = 
      0.00097 +/- 0.0001, HTN beta(1) = 0.10 +/- 0.01 and beta(2) = -0.00088 +/-
      0.0001; calf: NTN beta(1) = 0.12 +/- 0.01 and beta(2) = -0.00102 +/- 0.0001, HTN
      beta(1) = 0.11 +/- 0.01 and beta(2) = -0.00090 +/- 0.0001). However, at baseline,
      volume across all pressures (i.e., capacitance) was lower in the forearm (P < or
      = 0.01) and tended to be lower in the calf (P = 0.08) in HTN subjects. Venous
      compliance was not altered by any perturbation in either group. Forearm volume
      was increased during NTG in HTN subjects only. While venous compliance was
      similar between NTN and HTN adults, HTN adults have lower forearm venous
      capacitance (volume) which is increased with NTG. These data suggest that young
      HTN adults may have augmented venous smooth muscle tone compared with NTN
      controls.

PMID- 18635876
TI  - Hindlimb unloading elicits anhedonia and sympathovagal imbalance.
AB  - The hindlimb-unloaded (HU) rat model elicits cardiovascular deconditioning and
      simulates the physiological adaptations to microgravity or prolonged bed rest in
      humans. Although psychological deficits have been documented following bed rest
      and spaceflight in humans, few studies have explored the psychological effects of
      cardiovascular deconditioning in animal models. Given the bidirectional link
      established between cardiac autonomic imbalance and psychological depression in
      both humans and in animal models, we hypothesized that hindlimb unloading would
      elicit an alteration in sympathovagal tone and behavioral indexes of
      psychological depression. Male, Sprague-Dawley rats confined to 14 days of HU
      displayed anhedonia (a core feature of human depression) compared with casted
      control (CC) animals evidenced by reduced sucrose preference (CC: 81 +/- 2.9%
      baseline vs. HU: 58 +/- 4.5% baseline) and reduced (rightward shift) operant
      responding for rewarding electrical brain stimulation (CC: 4.4 +/- 0.3 muA vs.
      7.3 +/- 1.0 muA). Cardiac autonomic blockade revealed elevated sympathetic [CC: 
      54 +/- 14.1 change in (Delta) beats/min vs. HU: -118 +/- 7.6 Delta beats/min] and
      reduced parasympathetic (CC: 45 +/- 11.8 Delta beats/min vs. HU: 8 +/- 7.3 Delta
      beats/min) cardiac tone in HU rats. Heart rate variability was reduced (CC: 10 +/
      1.4 ms vs. HU: 7 +/- 0.7 ms), and spectral analysis of blood pressure indicated
      loss of total, low-, and high-frequency power, consistent with attenuated
      baroreflex function. These data indicate that cardiovascular deconditioning
      results in sympathovagal imbalance and behavioral signs consistent with
      psychological depression. These findings further elucidate the pathophysiological
      link between cardiovascular diseases and affective disorders.

PMID- 18635877
TI  - Neuromuscular plasticity during and following 3 wk of human forearm cast
      immobilization.
AB  - Prolonged reductions in muscle activity results in alterations in neuromuscular
      properties; however, the time course of adaptations is not fully understood, and
      many of the specific adaptations have not been identified. This study evaluated
      the temporal evolution of adaptations in neuromuscular properties during and
      following 3 wk of immobilization. We utilized a combination of techniques
      involving nerve stimulation and transcranial magnetic stimulation to assess
      changes in central activation of muscle, along with spinal (H reflex) and
      corticospinal excitability [i.e., motor-evoked potential (MEP) amplitude, silent
      period (SP)] and contractile properties in 10 healthy humans undergoing 3 wk of
      forearm immobilization and 9 control subjects. Immobilization induced deficits in
      central activation (85 +/- 3 to 67 +/- 7% ) that returned to baseline levels 1 wk
      after cast removal. The flexor carpii radialis MEP amplitude increased greater
      than twofold after the first week of immobilization and remained elevated
      throughout immobilization and 1 wk after cast removal. Additionally, we observed
      a prolongation of the SP 1 wk after cast removal compared with baseline (78.5 +/-
      7.1 to 98.2 +/- 8.7 ms). The contractile properties were also altered, since the
      rate of evoked force relaxation was slower following immobilization (-14.5 +/-
      1.4 to -11.3 +/- 1.0% peak force/ms), and remained depressed 1 wk after cast
      removal (-10.5 +/- 0.8% peak force/ms). These observations detail the time course
      of adaptations in corticospinal and contractile properties associated with disuse
      and illustrate the profound effect of immobilization on the human neuromuscular
      system as evidenced by the alterations in corticospinal excitability persisting 1
      wk following cast removal.

PMID- 18635879
TI  - Origins of the inhibiting effects of nasal CPAP on nonnutritive swallowing in
      newborn lambs.
AB  - The present study investigated the mechanism by which continuous positive airway
      pressure (CPAP) suppresses nonnutritive swallowing (NNS) during quiet sleep (QS)
      in newborn lambs. Eighteen full-term lambs were chronically instrumented and
      evenly distributed into three separate groups to determine the extent to which
      modulation of NNS may be attributed to stimulation of upper airway and/or
      bronchopulmonary mechanoreceptors. Six lambs were tracheotomized, six other lambs
      underwent a two-step bilateral intrathoracic vagotomy, and the remaining six
      lambs underwent chronic laryngotracheal separation (isolated upper airway group).
      Forty-eight hours after surgery, each nonsedated lamb underwent polysomnographic
      recordings on three consecutive days. States of alertness, NNS and respiratory
      movements were recorded. Results demonstrate that a CPAP of 6 cmH(2)O inhibited
      NNS during QS while administered directly on the lower airways and that
      bivagotomy prevented this inhibition. However, application of CPAP on the upper
      airways only also inhibited NNS during QS. Finally, the application of a CPAP of
      6 cmH(2)O had no systematic effect on NNS-breathing coordination (assessed by the
      respiratory phase preceding and following NNS). In conclusion, our results
      suggest that bronchopulmonary receptors are implicated in the inhibiting effects
      of nasal CPAP of 6 cmH(2)O on NNS in all our experimental conditions, whereas
      upper airway receptors are only implicated in certain conditions.

PMID- 18635878
TI  - Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced
      hepatic injury.
AB  - Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory
      response and organ dysfunction, the mechanisms responsible for these alterations
      are not clear. Using a potent selective inducible nitric oxide (NO) synthase
      inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO
      synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated
      whether inducible NO synthase plays any role in producing hepatic injury,
      inflammation, and changes of protein expression following trauma-hemorrhage. To
      investigate this, male Sprague-Dawley rats were subjected to midline laparotomy
      and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min)
      followed by fluid resuscitation. Animals were treated with either vehicle (DMSO)
      or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before
      resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation
      induced a marked hypotension and increase in markers of hepatic injury (i.e.,
      plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and
      nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor
      1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced
      neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein
      levels were also markedly increased following trauma-hemorrhage/resuscitation.
      Administration of the iNOS inhibitor 1400W significantly attenuated hypotension
      and expression of these mediators of hepatic injury induced by trauma
      hemorrhage/resuscitation. However, administration of L-NAME could not attenuate
      hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it
      improved mean blood pressure as did 1400W. These results indicate that increased
      expression of iNOS following trauma-hemorrhage plays an important role in the
      induction of hepatic damage under such conditions.

PMID- 18635880
TI  - Altered metabolic and transporter characteristics of vastus lateralis in chronic
      obstructive pulmonary disease.
AB  - To investigate energy metabolic and transporter characteristics in resting muscle
      of patients with moderate to severe chronic obstructive pulmonary disease [COPD;
      forced expiratory volume in 1 s (FEV(1)) = 42 +/- 6.0% (mean +/- SE)], tissue was
      extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with
      that of 12 healthy control subjects (FEV(1) = 114 +/- 3.4%). Compared with
      controls, lower (P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 +/- 0.65
      vs. 17.8 +/- 0.69) and phosphocreatine (81.3 +/- 2.3 vs. 69.1 +/- 4.2) were
      observed in COPD, which occurred in the absence of differences in the total
      adenine nucleotide and total creatine pools. Higher concentrations were observed
      in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6
      phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was
      not affected by the disease (289 +/- 20 vs. 269 +/- 20 mmol glucosyl units/kg dry
      wt). Although no difference between groups was observed for the glucose
      transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate
      transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1.
      These results indicate that in resting VL, moderate to severe COPD results in a
      reduction in phosphorylation potential, an apparent elevation of glycolytic flux
      rate, and a potential defect in glucose and lactate transport as a result of
      reduced levels of the principal isoforms.

PMID- 18635882
TI  - Leg intravenous pressure during head-up tilt.
AB  - Leg vascular resistance is calculated as the arterial-venous pressure gradient
      divided by blood flow. During orthostatic challenges it is assumed that the
      hydrostatic pressure contributes equally to leg arterial, as well as to leg
      venous pressure. Because of venous valves, one may question whether, during
      orthostatic challenges, a continuous hydrostatic column is formed and if leg
      venous pressure is equal to the hydrostatic pressure. The purpose of this study
      was, therefore, to measure intravenous pressure in the great saphenous vein of 12
      healthy individuals during 30 degrees and 70 degrees head-up tilt and compare
      this with the calculated hydrostatic pressure. The height difference between the
      heart and the right medial malleolus level represented the hydrostatic column.
      The results demonstrate that there were no differences between the measured
      intravenous pressure and the calculated hydrostatic pressure during 30 degrees
      (47.2 +/- 1.0 and 46.9 +/- 1.5 mmHg, respectively) and 70 degrees head-up tilt
      (83.9 +/- 0.9 and 85.1 +/- 1.2 mmHg, respectively). Steady-state levels of
      intravenous pressure were reached after 95 +/- 12 s during 30 degrees and 161 +/-
      15 s during 70 degrees head-up tilt. In conclusion, the measured leg venous
      pressure is similar to the calculated hydrostatic pressure during orthostatic
      challenges. Therefore, the assumption that hydrostatic pressure contributes
      equally to leg arterial as well as to leg venous pressure during orthostatic
      challenges can be made.

PMID- 18635881
TI  - GFP-expressing locus ceruleus neurons from Prp57 transgenic mice exhibit CO2/H+
      responses in primary cell culture.
AB  - The locus ceruleus (LC) contains neurons that increase their firing rate (FR) in
      vitro when exposed to elevated CO(2)/H(+) and have been proposed to influence the
      respiratory network to make compensatory adjustments in ventilation. Prp57
      transgenic mice express green fluorescent protein (GFP) in the LC and were used
      to isolate, culture, and target LC neurons for electrophysiological recording. We
      hypothesized that GFP-LC neurons would exhibit CO(2)/H(+) chemosensitivity under
      primary culture conditions, evidenced as a change in FR. This is the first study
      to quantify CO(2)/H(+) responses in LC neuron FR in cell culture. Neurons were
      continuously bathed with solutions containing antagonists of glutamate and GABA
      receptors, and the acid-base status was changed from control (5% CO(2); pH
      approximately 7.4) to hypercapnic acidosis (9% CO(2); pH approximately 7.2) and
      hypocapnic alkalosis (3% CO(2); pH approximately 7.6). FR was quantified during
      perforated patch current clamp recordings. Approximately 86% of GFP-LC neurons
      were stimulated, and approximately 14% were insensitive to changes in CO(2)/H(+).
      The magnitude of the response of these neurons depended on the baseline FR,
      ranging from 155.9 +/- 6% when FR started at 2.95 +/- 0.49 Hz to 381 +/- 55.6%
      when FR started at 1.32 +/- 0.31 Hz. These results demonstrate that cultured LC
      neurons from Prp57 transgenic mice retain functional sensing molecules necessary
      for CO(2)/H(+) responses. Prp57 transgenic mice will serve as a valuable model to
      delineate mechanisms involved in CO(2)/H(+) responsiveness in catecholaminergic
      neurons.

PMID- 18635883
TI  - Impact of diaphragmatic contraction on the stiffness of the canine mediastinum.
AB  - To assess the coupling between a particular hemidiaphragm and the individual
      lungs, the left and right phrenic nerves were separately stimulated in
      anesthetized dogs, and the mean changes in pleural pressure over the two lungs
      were evaluated by measuring the changes in airway opening pressure (DeltaPao) in
      the two bronchial trees. Stimulation induced a fall in Pao in both lungs.
      However, DeltaPao in the contralateral lung was only 65% of that in the
      ipsilateral lung. Thus, although the canine ventral mediastinum is a delicate
      structure, it sustained a significant pressure gradient. The hypothesis was then
      considered that this gradient was allowed to develop through the stretching and
      stiffening of the mediastinum caused by the descent of the diaphragm, and it was
      tested by measuring DeltaPao in the two lungs during isolated, unilateral
      contraction of the inspiratory intercostal muscles. In this condition, DeltaPao
      in the contralateral lung was 92% of that in the ipsilateral lung. A model
      analysis of the respiratory system led to the estimate that mediastinal elastance
      was approximately 25 times greater during hemidiaphragmatic contraction than
      during unilateral intercostal contraction. These observations indicate that 1) a
      particular hemidiaphragm has an expanding action on both lungs and 2) during
      contraction, however, it makes the mediastinum stiffer so that the pressure
      transmission from the ipsilateral to the contralateral pleural cavity is reduced.
      These observations imply that the mediastinum may play a significant role in
      determining the pressure-generating ability of the diaphragm.

PMID- 18635884
TI  - Assessment of physical activity in youth.
AB  - Despite much progress with physical activity assessment, the limitations
      concerning the accurate measurement of physical activity are often amplified in
      young people due to the cognitive, physiological, and biomechanical changes that
      occur during natural growth as well as a more intermittent pattern of habitual
      physical activity in youth compared with adults. This mini-review describes and
      compares methods to assess habitual physical activity in youth and discusses main
      issues regarding the use and interpretation of data collected with these
      techniques. Self-report instruments and movement sensing are currently the most
      frequently used methods for the assessment of physical activity in
      epidemiological research; others include heart rate monitoring and multisensor
      systems. Habitual energy expenditure can be estimated from these input measures
      with varying degree of uncertainty. Nonlinear modeling techniques, using
      accelerometry perhaps in combination with physiological parameters like heart
      rate or temperature, have the greatest potential for increasing the prediction
      accuracy of habitual physical activity energy expenditure. Although multisensor
      systems may be more accurate, this must be balanced against feasibility, a
      balance that shifts with technological and scientific advances and should be
      considered at the beginning of every new study.

PMID- 18635885
TI  - Novel endo-alpha-N-acetylgalactosaminidases with broader substrate specificity.
AB  - In an effort to identify novel endo-alpha-N-acetylgalactosaminidases (endo-alpha
      GalNAcases), four potential genes were cloned. Three of the expressed proteins
      EngEF from Enterococcus faecalis, EngPA from Propionibacterium acnes, and EngCP
      from Clostridium perfringens were purified and characterized. Their substrate
      specificity was investigated and compared to the commercially available endo
      alpha-GalNAcases from Streptococcus pneumoniae (EngSP) and Alcaligenes sp.
      (EngAL). All enzymes were incubated with various synthetic substrates, and
      natural glycoproteins and the released sugars were detected by colorimetric assay
      and thin layer chromatography analysis. The Core 1 disaccharide Gal beta
      1,3GalNAc alpha 1pNP was the most rapidly hydrolyzed substrate by all enzymes
      tested. EngEF exhibited the highest k(cat) for this substrate. EngEF and EngPA
      were also able to fully hydrolyze the Core 3 disaccharide GlcNAc beta 1,3GalNAc
      alpha 1pNP. This is the first report of endo-alpha-GalNAcases EngEF and EngPA
      acting on Core 3 in addition to Core 1 O-glycans. Interestingly, there were no
      significant differences in transglycosylation activities when Gal beta 1,3GalNAc
      alpha 1pNP or GlcNAc beta 1,3GalNAc alpha 1pNP was incubated with various 1
      alkanols in the presence of the endo-alpha-GalNAcases tested in this work.

PMID- 18635886
TI  - Alterations of the arginine metabolome in asthma.
AB  - RATIONALE: As the sole nitrogen donor in nitric oxide (NO) synthesis and key
      intermediate in the urea cycle, arginine and its metabolic pathways are
      integrally linked to cellular respiration, metabolism, and inflammation.
      OBJECTIVES: We hypothesized that arginine (Arg) bioavailability would be
      associated with airflow abnormalities and inflammation in subjects with asthma,
      and would be informative for asthma severity. METHODS: Arg bioavailability was
      assessed in subjects with severe and nonsevere asthma and healthy control
      subjects by determination of plasma Arg relative to its metabolic products,
      ornithine and citrulline, and relative to methylarginine inhibitors of NO
      synthases, and by serum arginase activity. Inflammatory parameters, including
      fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens,
      bronchoalveolar lavage, and blood eosinophils, were also evaluated. MEASUREMENTS
      AND MAIN RESULTS: Subjects with asthma had greater Arg bioavailability, but also
      increased Arg catabolism compared with healthy control subjects, as evidenced by
      higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability
      was positively associated with Fe(NO) only in healthy control subjects; Arg
      bioavailability was unrelated to Fe(NO) or other inflammatory parameters in
      severe or nonsevere asthma. Inflammatory parameters were related to airflow
      obstruction and reactivity in nonsevere asthma, but not in severe asthma.
      Conversely, Arg bioavailability was related to airflow obstruction in severe
      asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg
      bioavailabilty predict airflow obstruction only in severe asthma. CONCLUSIONS:
      Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation;
      however, Arg bioavailability is strongly associated with airflow abnormalities in
      severe asthma.

PMID- 18635887
TI  - Surfactant protein D protects against acute hyperoxic lung injury.
AB  - RATIONALE: Surfactant protein D (SP-D) is a member of the collectin family of
      soluble, innate, host defense molecules with demonstrated immunomodulatory
      properties in vitro. Constitutive absence of SP-D in mice is associated with lung
      inflammation, alteration in surfactant lipid homeostasis, and increased oxidative
      nitrative stress. OBJECTIVES: To test the hypothesis that SP-D would protect
      against acute lung injury from hyperoxia in vivo. METHODS: Transgenic mice
      overexpressing rat SP-D constitutively (SP-D OE) or conditionally via regulation
      with doxycycline (SP-D Dox-on) were subjected to continuous hyperoxic challenge
      for up to 14 days. MEASUREMENTS AND MAIN RESULTS: Compared with littermate
      control mice (wild-type [WT]), SP-D OE mice exposed to 80% O(2) demonstrated
      substantially increased survival accompanied by significant reductions in wet to
      dry lung ratios and bronchoalveolar lavage (BAL) protein. Although SP-D OE and WT
      mice exhibited a twofold increase in total BAL cells and neutrophilia in response
      to hyperoxia, the SP-D OE group had lower levels of BAL proinflammatory cytokines
      and chemokines, including IL-6, tumor necrosis factor-alpha, and monocyte
      chemotactic protein-1; increased mRNA levels of the transcription factor NF-E2
      related factor-2 (NRF-2) and phase 2 antioxidants hemoxygenase-1 (HO-1),
      glutathione peroxidase-2 (GPx-2) and NAD(P)H quinone oxidoreductase-1 (Nqo-1);
      and decreases in lung tissue thiobarbituric acid-reactive substances. As proof of
      principle, the protective role of SP-D on hyperoxic injury was confirmed as SP-D
      Dox-on mice exposed to 85% O(2) demonstrated increased mortality upon withdrawal
      of doxycycline. CONCLUSIONS: Local expression of SP-D protects against hyperoxic
      lung injury through modulation of proinflammatory cytokines and antioxidant
      enzymatic scavenger systems.

PMID- 18635888
TI  - Telomere shortening in familial and sporadic pulmonary fibrosis.
AB  - RATIONALE: Heterozygous mutations in the coding regions of the telomerase genes,
      TERT and TERC, have been found in familial and sporadic cases of idiopathic
      interstitial pneumonia. All affected patients with mutations have short
      telomeres. OBJECTIVES: To test whether telomere shortening is a frequent
      mechanism underlying pulmonary fibrosis, we have characterized telomere lengths
      in subjects with familial or sporadic disease who do not have coding mutations in
      TERT or TERC. METHODS: Using a modified Southern blot assay, the telomerase
      restriction fragment length method, and a quantitative polymerase chain reaction
      assay we have measured telomere lengths of genomic DNA isolated from circulating
      leukocytes from normal control subjects and subjects with pulmonary fibrosis.
      MEASUREMENTS AND MAIN RESULTS: All affected patients with telomerase mutations,
      including case subjects heterozygous for newly reported mutations in TERT, have
      short telomere lengths. A significantly higher proportion of probands with
      familial pulmonary fibrosis (24%) and sporadic case subjects (23%) in which no
      coding mutation in TERT or TERC was found had telomere lengths less than the 10th
      percentile when compared with control subjects (P = 2.6 x 10(-8)). Pulmonary
      fibrosis affectation status was significantly associated with telomerase
      restriction fragment lengths, even after controlling for age, sex, and ethnicity
      (P = 6.1 x 10(-11)). Overall, 25% of sporadic cases and 37% of familial cases of
      pulmonary fibrosis had telomere lengths less than the 10th percentile.
      CONCLUSIONS: A significant fraction of individuals with pulmonary fibrosis have
      short telomere lengths that cannot be explained by coding mutations in
      telomerase. Telomere shortening of circulating leukocytes may be a marker for an
      increased predisposition toward the development of this age-associated disease.

PMID- 18635889
TI  - Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in
      sepsis.
AB  - RATIONALE: Polymorphisms affecting Toll-like receptor (TLR)-mediated responses
      could predispose to excessive inflammation during an infection and contribute to
      an increased risk for poor outcomes in patients with sepsis. OBJECTIVES: To
      identify hypermorphic polymorphisms causing elevated TLR-mediated innate immune
      cytokine and chemokine responses and to test whether these polymorphisms are
      associated with increased susceptibility to death, organ dysfunction, and
      infections in patients with sepsis. METHODS: We screened single-nucleotide
      polymorphisms (SNPs) in 43 TLR-related genes to identify variants affecting TLR
      mediated inflammatory responses in blood from healthy volunteers ex vivo. The SNP
      associated most strongly with hypermorphic responses was tested for associations
      with death, organ dysfunction, and type of infection in two studies: a nested
      case-control study in a cohort of intensive care unit patients with sepsis, and a
      case-control study using patients with sepsis, patients with sepsis-related acute
      lung injury, and healthy control subjects. MEASUREMENTS AND MAIN RESULTS: The SNP
      demonstrating the most hypermorphic effect was the G allele of TLR1(-7202A/G)
      (rs5743551), which associated with elevated TLR1-mediated cytokine production (P
      < 2 x 10(-20)). TLR1(-7202G) marked a coding SNP that causes higher TLR1-induced
      NF-kappaB activation and higher cell surface TLR1 expression. In the cohort of
      patients with sepsis TLR1(-7202G) predicted worse organ dysfunction and death
      (odds ratio, 1.82; 95% confidence interval, 1.07-3.09). In the case-control study
      TLR1(-7202G) was associated with sepsis-related acute lung injury (odds ratio,
      3.40; 95% confidence interval, 1.59-7.27). TLR1(-7202G) also associated with a
      higher prevalence of gram-positive cultures in both clinical studies.
      CONCLUSIONS: Hypermorphic genetic variation in TLR1 is associated with increased
      susceptibility to organ dysfunction, death, and gram-positive infection in
      sepsis.

PMID- 18635890
TI  - The Pittsburgh Lung Screening Study (PLuSS): outcomes within 3 years of a first
      computed tomography scan.
AB  - RATIONALE: The role of computed tomography (CT) screening for lung cancer is
      controversial, currently under study, and not yet fully elucidated. OBJECTIVES:
      To report findings from initial and 1-year repeat screening low-radiation-dose CT
      of the chest and 3-year outcomes for 50- to 79-year-old current and ex-smokers in
      the Pittsburgh Lung Screening Study (PLuSS). METHODS: Notified of findings on
      screening CT, subjects received diagnostic advice from both study and personal
      physicians. Tracking subjects for up to three years since initial screening, we
      obtained medical records to document diagnostic procedures, lung cancer
      diagnoses, and deaths. MEASUREMENTS AND MAIN RESULTS: 3,642 and 3,423 subjects
      had initial and repeat screening. A total of 1,477 (40.6% of 3,624) were told
      about noncalcified lung nodules on the initial screening and, before repeat
      screening, 821 (55.6% of 1,477, 22.5% of 3,642) obtained one or more subsequent
      diagnostic imaging studies (CT, positron emission tomography [PET], or PET-CT).
      Tracking identified 80 subjects with lung cancer, including 53 subjects with
      tumor seen at initial screening. In all, 36 subjects (1.0% of the 3,642
      screened), referred for abnormalities on either the initial or repeat screening,
      had a major thoracic surgical procedure (thoracotomy, video-assisted
      thoracoscopic surgery [VATS], median sternotomy, or mediastinoscopy) leading to a
      noncancer final diagnosis. Out of 82 subjects with thoracotomy or VATS to exclude
      malignancy in a lung nodule, 28 (34.1%) received a noncancer final diagnosis.
      Forty of 69 (58%) subjects with non-small cell lung cancer had stage I disease at
      diagnosis. CONCLUSIONS: Though leading to the discovery of early stage lung
      cancer, CT screening also led to many diagnostic follow-up procedures, including
      major thoracic surgical procedures with noncancer outcomes.

PMID- 18635892
TI  - Body mass and glucocorticoid response in asthma.
AB  - RATIONALE: Obesity may alter glucocorticoid response in asthma. OBJECTIVES: To
      evaluate the relationship between body mass index (BMI, kg/m(2)) and
      glucocorticoid response in subjects with and without asthma. METHODS: Nonsmoking
      adult subjects underwent characterization of lung function, BMI, and spirometric
      response to prednisone. Dexamethasone (DEX, 10(-6) M)-induced mitogen-activated
      protein kinase phosphatase-1 (MKP-1) and baseline tumor necrosis factor (TNF)
      alpha expression were evaluated by polymerase chain reaction in peripheral blood
      mononuclear cells (PBMCs) and bronchoalveolar lavage cells. The relationship
      between BMI and expression of MKP-1 and TNF-alpha was analyzed. MEASUREMENTS AND
      MAIN RESULTS: A total of 45 nonsmoking adults, 33 with asthma (mean [SD] FEV(1)%
      of 70.7 [9.8]%) and 12 without asthma were enrolled. DEX-induced PBMC MKP-1
      expression was reduced in overweight/obese versus lean patients with asthma, with
      mean (+/- SEM) fold-induction of 3.11 (+/-0.46) versus 5.27 (+/-0.66),
      respectively (P = 0.01). In patients with asthma, regression analysis revealed a 
      0.16 (+/-0.08)-fold decrease in DEX-induced MKP-1 per unit BMI increase (P =
      0.04). PBMC TNF-alpha expression increased as BMI increased in subjects with
      asthma, with a 0.27 unit increase in log (TNF-alpha [ng/ml]) per unit BMI
      increase (P = 0.01). The ratio of PBMC log (TNF-alpha):DEX-induced MKP-1 also
      increased as BMI increased in patients with asthma (+0.09 +/- 0.02; P = 0.004).
      In bronchoalveolar lavage cells, DEX-induced MKP-1 expression was also reduced in
      overweight/obese versus lean patients with asthma (1.36 +/- 0.09-fold vs. 1.76 +/
      0.15-fold induction; P = 0.05). Similar findings were not observed in control
      subjects without asthma. CONCLUSIONS: Elevated BMI is associated with blunted in
      vitro response to dexamethasone in overweight and obese patients with asthma.

PMID- 18635891
TI  - Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic
      pulmonary fibrosis.
AB  - RATIONALE: The molecular pathomechanisms underlying idiopathic pulmonary fibrosis
      (IPF) are elusive, but chronic epithelial injury has recently been suggested as
      key event. OBJECTIVES: We investigated the possible implication of endoplasmic
      reticulum (ER) stress-mediated apoptosis in sporadic IPF. METHODS: We analyzed
      peripheral explanted lung tissues from patients with sporadic IPF (n = 24),
      chronic obstructive pulmonary disease (COPD) (n = 9), and organ donors (n = 12)
      for expression of major ER stress mediators and apoptosis markers by means of
      immunoblotting, semiquantitative reverse transcription-polymerase chain reaction,
      immunohistochemistry, and the TUNEL method. MEASUREMENTS AND MAIN RESULTS:
      Compared with COPD and donor lungs, protein levels of ER stress mediators, such
      as processed p50 activating transcription factor (ATF)-6 and ATF-4 and the
      apoptosis-inductor CHOP (C/EBP-homologous protein), as well as transcript levels
      of spliced X-box binding protein (XBP)-1, were significantly elevated in lung
      homogenates and type II alveolar epithelial cells (AECIIs) of IPF lungs.
      Proapoptotic, oligomeric forms of Bax, which play a key role in ER stress
      mediated apoptosis downstream of CHOP induction, as well as caspase-3 cleavage,
      could be detected in IPF lungs. By means of immunohistochemistry, exclusive
      induction of active ATF-6, ATF-4, and CHOP in AECIIs was encountered in IPF but
      not in COPD or donor lungs. Immunoreactivity was most prominent in the epithelium
      near dense zones of fibrosis and fibroblast foci, where these ER stress markers
      colocalized with markers of apoptosis (TUNEL, cleaved caspase-3). CONCLUSIONS:
      Severe ER stress response in the AECIIs of patients with sporadic IPF may
      underlie the apoptosis of this cell type and development of fibrosis in this
      disease.

PMID- 18635893
TI  - Acoustic backscatter and effective scatterer size estimates using a 2D CMUT
      transducer.
AB  - Compared to conventional piezoelectric transducers, new capacitive
      microfabricated ultrasonic transducer (CMUT) technology is expected to offer a
      broader bandwidth, higher resolution and advanced 3D/4D imaging inherent in a 2D
      array. For ultrasound scatterer size imaging, a broader frequency range provides
      more information on frequency-dependent backscatter, and therefore, generally
      more accurate size estimates. Elevational compounding, which can significantly
      reduce the large statistical fluctuations associated with parametric imaging,
      becomes readily available with a 2D array. In this work, we show phantom and in
      vivo breast tumor scatterer size image results using a prototype 2D CMUT
      transducer (9 MHz center frequency) attached to a clinical scanner. A uniform
      phantom with two 1 cm diameter spherical inclusions of slightly smaller scatterer
      size was submerged in oil and scanned by both the 2D CMUT and a conventional
      piezoelectric linear array transducer. The attenuation and scatterer sizes of the
      sample were estimated using a reference phantom method. RF correlation analysis
      was performed using the data acquired by both transducers. The 2D CMUT results
      indicate that at a 2 cm depth (near the transmit focus for both transducers) the
      correlation coefficient reduced to less than 1/e for 0.2 mm lateral or 0.25 mm
      elevational separation between acoustic scanlines. For the conventional array
      this level of decorrelation requires a 0.3 mm lateral or 0.75 mm elevational
      translation. Angular and/or elevational compounding is used to reduce the
      variance of scatterer size estimates. The 2D array transducer acquired RF signals
      from 140 planes over a 2.8 cm elevational direction. If no elevational
      compounding is used, the fractional standard deviation of the size estimates is
      about 12% of the mean size estimate for both the spherical inclusion and the
      background. Elevational compounding of 11 adjacent planes reduces it to 7% for
      both media. Using an experimentally estimated attenuation of 0.6 dB cm(-1) MHz(
      1), scatterer size estimates for an in vivo breast tumor also demonstrate
      improvements using elevational compounding with data from the 2D CMUT transducer.

PMID- 18635894
TI  - Analysis of the measurement precision of an amorphous silicon EPID used for MLC
      leaf position quality control and the long-term calibration stability of an
      optically controlled MLC.
AB  - Electronic portal imaging devices (EPIDs) have been shown to be suitable for
      multileaf collimator (MLC) leaf positioning quality control (QC). In our centre,
      a continuous dataset is available of 2 years of film measurements followed by 3
      years of EPID measurements on five MLC-equipped linear accelerators of identical
      head design. The aim of this work was to analyse this unique dataset in order to
      determine the relative precision of film and EPID for MLC leaf positioning
      measurements and to determine the long-term stability of the MLC calibration. The
      QC dataset was examined and periods without MLC adjustments that contained at
      least four successive collimator position measurements (a minimum of 6 months)
      were identified. By calculating the standard deviations (SD) of these results,
      the reproducibility of the measurements can be determined. Comparison of the film
      and EPID results enables their relative measurement precision to be assessed; on
      average film gave an SD of 0.52 mm compared to 0.13 mm for EPIDs. The MLC and
      conventional collimator results were compared to assess MLC calibration
      stability; on average, for EPID measurements, the MLC gave an SD of 0.12 mm
      compared to 0.14 mm for a conventional collimator. The long-term relative
      individual leaf positions were compared and found to vary between 0.07 and 0.15
      mm implying that they are stable over long time periods. These results suggest
      that the calibration of an optically controlled MLC is inherently very stable
      between disturbances to the optical system which normally occur on service days.

PMID- 18635896
TI  - Noninvasive photoacoustic imaging of the developing vasculature during early
      tumor growth.
AB  - In this study, we monitor the progress of vasculature in early tumor growth using
      photoacoustic imaging over a 20 day period after subcutaneous inoculation of
      breast cancer tumor cells in a mouse. With 532 nm laser pulses employed as an
      irradiation source, the photoacoustic images were obtained through the
      photoacoustic signals received by a hydrophone in orthogonal mode. The
      morphological characteristics of vasculature in tumor region are clearly resolved
      in the photoacoustic images, and the change in structure as well as the increase
      in density can be identified. Moreover, the average photoacoustic signal strength
      of vasculature in tumor region, which is highly correlated with the total
      hemoglobin concentration of blood, is enhanced during early tumor growth. These
      results indicate the feasibility of detecting early stage tumor and monitoring
      the progress of anti-angiogenic therapy by photoacoustic imaging.

PMID- 18635895
TI  - Intensity-modulated x-ray (IMXT) versus proton (IMPT) therapy for theragnostic
      hypoxia-based dose painting.
AB  - In this work the abilities of intensity-modulated x-ray therapy (IMXT) and
      intensity-modulated proton therapy (IMPT) to deliver boosts based on theragnostic
      imaging were assessed. Theragnostic imaging is the use of functional or molecular
      imaging data for prescribing radiation dose distributions. Distal gradient
      tracking, an IMPT method designed for the delivery of non-uniform dose
      distributions, was assessed. Dose prescriptions for a hypoxic region in a head
      and neck squamous cell carcinoma patient were designed to either uniformly boost
      the region or redistribute the dose based on positron emission tomography (PET)
      images of the (61)Cu(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) ((61)Cu-ATSM)
      hypoxia surrogate. Treatment plans for the prescriptions were created for four
      different delivery methods: IMXT delivered with step-and-shoot and with helical
      tomotherapy, and IMPT delivered with spot scanning and distal gradient tracking.
      IMXT and IMPT delivered comparable dose distributions within the boost region for
      both uniform and redistributed theragnostic boosts. Normal tissue integral dose
      was lower by a factor of up to 3 for IMPT relative to the IMXT. For all delivery
      methods, the mean dose to the nearby organs at risk changed by less than 2 Gy for
      redistributed versus uniform boosts. The distal gradient tracking method resulted
      in comparable plans to the spot scanning method while reducing the number of
      proton beam spots by a factor of over 3.

PMID- 18635897
TI  - Quantitative assessment of the physical potential of proton beam range
      verification with PET/CT.
AB  - A recent clinical pilot study demonstrated the feasibility of offline PET/CT
      range verification for proton therapy treatments. In vivo PET measurements are
      challenged by blood perfusion, variations of tissue compositions, patient motion
      and image co-registration uncertainties. Besides these biological and treatment
      specific factors, the accuracy of the method is constrained by the underlying
      physical processes. This phantom study distinguishes physical factors from other
      factors, assessing the reproducibility, consistency and sensitivity of the PET/CT
      range verification method. A spread-out Bragg-peak (SOBP) proton field was
      delivered to a phantom consisting of poly-methyl methacrylate (PMMA), lung and
      bone equivalent material slabs. PET data were acquired in listmode at a
      commercial PET/CT scanner available within 10 min walking distance from the
      proton therapy unit. The measured PET activity distributions were compared to
      simulations of the PET signal based on Geant4 and FLUKA Monte Carlo (MC) codes.
      To test the reproducibility of the measured PET signal, data from two independent
      measurements at the same geometrical position in the phantom were compared.
      Furthermore, activation depth profiles within identical material arrangements but
      at different positions within the irradiation field were compared to test the
      consistency of the measured PET signal. Finally, activation depth profiles
      through air/lung, air/bone and lung/bone interfaces parallel as well as at 6
      degrees to the beam direction were studied to investigate the sensitivity of the
      PET/CT range verification method. The reproducibility and the consistency of the
      measured PET signal were found to be of the same order of magnitude. They
      determine the physical accuracy of the PET measurement to be about 1 mm. However,
      range discrepancies up to 2.6 mm between two measurements and range variations up
      to 2.6 mm within one measurement were found at the beam edge and at the edge of
      the field of view (FOV) of the PET scanner. PET/CT range verification was found
      to be able to detect small range modifications in the presence of complex tissue
      inhomogeneities. This study indicates the physical potential of the PET/CT
      verification method to detect the full-range characteristic of the delivered dose
      in the patient.

PMID- 18635898
TI  - Coherent normalization of finger strontium XRF measurements: feasibility and
      limitations.
AB  - A non-invasive in vivo x-ray fluorescence (XRF) method of measuring bone
      strontium concentrations has previously been reported as a potential diagnostic
      tool able to detect strontium concentration in the finger and ankle bones. The
      feasibility of coherent normalization for (125)I-source-based finger bone
      strontium x-ray fluorescence (XRF) measurements is assessed here by theoretical
      considerations and Monte Carlo simulations. Normalization would have several
      advantages, among which are the correction for the signal attenuation by the
      overlying soft tissue, and intersubject variability in the bone size and shape.
      The coherent normalization of bone strontium XRF measurements presents several
      challenges dictated by the behaviour of the coherent cross section and mass
      attenuation coefficient at the energies involved. It was found that the coherent
      normalization alone with either 22.1 keV or 35.5 keV photons was not successful
      in correcting for the overlying soft tissue attenuation. However, it was found
      that the coherent peak at 35.5 keV was able to correct effectively for
      variability in the finger bone size between people. Thus, it is suggested that,
      if the overlying soft tissue thickness can be obtained by means of an independent
      measurement, the 35.5 keV peak can be used to correct for the bone size, with an
      overall accuracy of the normalization process of better than 10%.

PMID- 18635899
TI  - Design and performance of a multi-pinhole collimation device for small animal
      imaging with clinical SPECT and SPECT-CT scanners.
AB  - A multi-pinhole collimation device is developed that uses the gamma camera
      detectors of a clinical SPECT or SPECT-CT scanner to produce high-resolution
      SPECT images. The device consists of a rotating cylindrical collimator having 22
      tungsten pinholes with 0.9 mm diameter apertures and an animal bed inside the
      collimator that moves linearly to provide helical or ordered-subsets axial
      sampling. CT images also may be acquired on a SPECT-CT scanner for purposes of
      image co-registration and SPECT attenuation correction. The device is placed on
      the patient table of the scanner without attaching to the detectors or scanner
      gantry. The system geometry is calibrated in-place from point source data and is
      then used during image reconstruction. The SPECT imaging performance of the
      device is evaluated with test phantom scans. Spatial resolution from
      reconstructed point source images is measured to be 0.6 mm full width at half
      maximum or better. Micro-Derenzo phantom images demonstrate the ability to
      resolve 0.7 mm diameter rod patterns. The axial slabs of a Micro-Defrise phantom
      are visualized well. Collimator efficiency exceeds 0.05% at the center of the
      field of view, and images of a uniform phantom show acceptable uniformity and
      minimal artifact. The overall simplicity and relatively good imaging performance
      of the device make it an interesting low-cost alternative to dedicated small
      animal scanners.

PMID- 18635900
TI  - Baseline cardiovascular risk factors and stroke mortality by municipality
      population size in a 19-year follow-up study-NIPPON DATA80.
AB  - The urban-rural difference in cardiovascular risk factors and stroke mortality
      throughout Japan was examined in a cohort by using hierarchical data structure.
      The subjects were 9,309 men and women aged > or = 30 years who were residents of
      294 areas in 211 municipalities of Japan in 1980; they were followed up until
      1999. The population sizes of the municipalities in which the aforementioned
      areas were located were used to distinguish between urban and rural areas. We
      applied multilevel modeling to take into account the hierarchical data structure
      of individuals (subjects) (level 1) nested within areas (level 2). Statistically
      significant differences were observed in the case of medium (30,000-300,000) and
      small (<30,000) municipality populations compared with large (> or =300,000)
      municipality populations with regard to the following parameters: body mass index
      in men, serum total cholesterol in both men and women, and daily alcohol drinking
      in women. The values or frequencies of these cardiovascular risk factors were
      significantly higher in large populations. Meanwhile, age-adjusted odds ratios
      for stroke mortality in the areas in the medium and small municipalities compared
      with those in the areas in the large municipalities were 1.31 (95% confidence
      interval (CI) 0.81-2.13) and 1.40 (95% CI 0.87-2.24) in men, and 1.32 (95% CI
      0.79-2.20) and 1.62 (95% CI 0.99-2.65) in women, respectively. The results of
      multivariate analyses adjusted for age, body mass index, total cholesterol,
      diabetes, hypertension, current smoking, and daily alcohol consumption did not
      change materially. In conclusion, stroke mortality tended to be higher in rural
      areas than in urban areas in Japan, especially among women.

PMID- 18635901
TI  - Epidemiologic features of Kawasaki disease in Japan: results from the nationwide
      survey in 2005-2006.
AB  - BACKGROUND: The most recent epidemiologic features of Kawasaki disease are
      unknown. METHODS: The 19th nationwide survey of the disease was conducted in
      2007, targeting patients who were affected by this disease in 2005 and 2006. All
      pediatric departments in hospitals with 100 or more beds and pediatric hospitals
      were asked to report all Kawasaki disease patients during the 2 survey years.
      RESULTS: From 1543 departments and hospitals, a total of 20475 patients (10041 in
      2005 and 10434 in 2006) were reported. There were 11892 male patients and 8583
      female patients. The average annual incidence rate was 184.6 per 100000 children
      aged 0-4 years. The number of patients and the incidence rate have increased
      significantly during the past 12 years. The age-specific incidence rate was
      distributed monomodally with a peak at 6-8 months of age. The prevalence of
      cardiac lesions in the acute phase of the disease and of cardiac sequelae were
      higher among infants and old patients. CONCLUSION: The number of patients with
      Kawasaki disease and its incidence rate in Japan are continuously increasing.

PMID- 18635902
TI  - Daily magnesium intake and serum magnesium concentration among Japanese people.
AB  - BACKGROUND: The vitamins and minerals that are deficient in the daily diet of a
      normal adult remain unknown. To answer this question, we conducted a population
      survey focusing on the relationship between dietary magnesium intake and serum
      magnesium level. METHODS: The subjects were 62 individuals from Fukui Prefecture
      who participated in the 1998 National Nutrition Survey. The survey investigated
      the physical status, nutritional status, and dietary data of the subjects.
      Holidays and special occasions were avoided, and a day when people are most
      likely to be on an ordinary diet was selected as the survey date. RESULTS: The
      mean (+/-standard deviation) daily magnesium intake was 322 (+/-132), 323 (+/
      163), and 322 (+/-147) mg/day for men, women, and the entire group, respectively.
      The mean (+/-standard deviation) serum magnesium concentration was 20.69 (+/
      2.83), 20.69 (+/-2.88), and 20.69 (+/-2.83) ppm for men, women, and the entire
      group, respectively. The distribution of serum magnesium concentration was
      normal. Dietary magnesium intake showed a log-normal distribution, which was then
      transformed by logarithmic conversion for examining the regression coefficients.
      The slope of the regression line between the serum magnesium concentration (Y
      ppm) and daily magnesium intake (X mg) was determined using the formula Y = 4.93
      (log(10)X) + 8.49. The coefficient of correlation (r) was 0.29. A regression line
      (Y = 14.65X + 19.31) was observed between the daily intake of magnesium (Y mg)
      and serum magnesium concentration (X ppm). The coefficient of correlation was
      0.28. CONCLUSION: The daily magnesium intake correlated with serum magnesium
      concentration, and a linear regression model between them was proposed.

PMID- 18635903
TI  - Gene identification and characterization of the pyridoxine degradative enzyme
      alpha-(N-acetylaminomethylene)succinic acid amidohydrolase from Mesorhizobium
      loti MAFF303099.
AB  - We have found for the first time that a chromosomal gene, mlr6787, in
      Mesorhizobium loti encodes the pyridoxine degradative enzyme alpha-(N
      acetylaminomethylene)succinic acid (AAMS) amidohydrolase. The recombinant enzyme
      expressed in Escherichia coli cells was homogeneously purified and characterized.
      The enzyme consisted of two subunits each with a molecular mass of 34,000+/-1,000
      Da, and exhibited Km and kcat values of 53.7+/-6 microM and 307.3+/-12 min(-1),
      respectively. The enzyme required no cofactor or metal ion. The primary structure
      of AAMS amidohydrolase was elucidated for the first time here. The primary
      structure of the enzyme protein showed no significant identity to those of known
      hydrolase proteins and low homology to those of fluoroacetate dehalogenase (PDB
      code, 1Y37), haloalkane dehalogenase (1K5P), and aryl esterase (1VA4).

PMID- 18635904
TI  - Royal jelly peptides inhibit lipid peroxidation in vitro and in vivo.
AB  - Royal jelly peptides (RJPx) isolated from hydrolysates of water-soluble royal
      jelly proteins prepared with protease P exhibited significantly stronger hydroxyl
      radical-scavenging activity (p<0.001), and antioxidant activity against lipid
      peroxidation (LPO, p<0.001), than did water-soluble royal jelly protein (WSRJP)
      in vitro. We also investigated the in vivo antioxidant activity of RJPx against
      ferric nitrilotriacetate (Fe-NTA)-induced LPO. Male Wistar rats were divided into
      a control group (Group C), an Fe-NTA group (Group Fe), and an Fe-NTA with RJPx
      group (Group Fe+R). Rats in Group Fe+R were fed RJPx (2 g/kg body weight) daily
      for 5 wk. Fe-NTA (8 mg Fe/kg body weight) was then intraperitoneally injected,
      and serum lipid levels were examined 2 h later. Serum total cholesterol (TC)
      levels were lower (p<0.05) while low-density lipoprotein (LDL) and LPO were
      significantly higher (p<0.01) in Group Fe than in Group C. TC (p<0.05) and LPO
      levels (p<0.01) were lower in Group Fe+R than in Group Fe. Our data suggest that
      RJPx may inhibit LPO both in vitro and in vivo.

PMID- 18635905
TI  - Myo-inositol treatment increases serum plasmalogens and decreases small dense
      LDL, particularly in hyperlipidemic subjects with metabolic syndrome.
AB  - BACKGROUND AND AIM: We have previously shown that serum plasmalogen levels
      positively correlate with HDL, and significantly decrease with aging, and may be
      related to LDL particle size. The objective of the present study was to
      investigate the effects of increased serum plasmalogens on lipidosis,
      particularly the appearance of atherogenic small dense LDL (sdLDL), of subjects
      with hyperlipidemia and metabolic syndrome (MetS). METHODS AND RESULTS: The
      effects of increased serum plasmalogen levels, induced by 2 wk of myo-inositol
      treatment, on several clinical and biochemical parameters were examined in 17
      hyperlipidemic subjects including some with MetS. After myo-inositol treatment,
      significant increases in plasmalogen-related parameters, particularly ChoPlas,
      and significant decreases in atherogenic cholesterols including sdLDL, were
      observed. Among the hyperlipidemic subjects treated with myo-inositol, compared
      to subjects without MetS, subjects with MetS had a significant increase in
      plasmalogens and a tendency towards reduced sdLDL, high sensitivity C-reactive
      protein (hsCRP), and blood glucose levels. Correlation analyses between the
      measured parameters showed that plasmalogens, as well as HDL, function as
      beneficial factors, and that sdLDL is a very important risk factor that shows
      positive correlations with many other risk factors. CONCLUSION: These results
      suggest that increased plasmalogen biosynthesis and/or serum levels are
      especially effective in improving MetS among hyperlipidemic subjects with MetS.

PMID- 18635906
TI  - Modulation of maltose preference by selection from dextrin, maltose and glucose
      diets in zinc-deficient rats.
AB  - This study examined whether the chain length of glucose in the diet could affect
      the selection of foods by Zn-adequate and Zn-deficient rats. Dextrin, maltose and
      glucose were used as sources of carbohydrate in the diet and the selection
      patterns of the rats were analyzed for 28 d by a 3-choice selection. Diets
      provided as a set of three either Zn-adequate or Zn-deficient diets were rotated
      daily. The Zn-adequate control rats selected widely from the three diets
      throughout the 28 d. In contrast, rats fed a Zn-deficient diet selected
      exclusively and continuously the dextrin diet or dextrin and glucose diets from
      the three diets over the experimental periods. The average daily total food
      intakes of rats fed a Zn-deficient diet were very significantly decreased. The
      selections of dextrin, maltose and glucose diets in the 3-choice methods of the
      control rats were 5.7+/-1.6(b), 5.8+/-2.0(b) and 2.7+/-0.9(a) g/d, respectively
      (p<0.05), and those of the Zn-deficient rats were 6.4+/-2.5(c), 0.8+/-1.3(a) and
      2.6+/-1.4(b) g/d, respectively (p<0.05). The ratios of the selected maltose-diet
      in the Zn-adequate control and the Zn-deficient rats were 40.8+/-13.8 and 9.0+/
      15.6%, respectively (p<0.01) and those of the dextrin-diet were 40.3+/-11.4 and
      63.0+/-22.3%, respectively (p<0.05). The decreased preference for the maltose
      diet in the Zn-deficient rats may reflect the increased selection of the dextrin
      diet.

PMID- 18635907
TI  - Comparison of effects of dietary unesterified and esterified plant sterols on
      cholesterol absorption in rats.
AB  - Effects of dietary unesterified plant sterols and plant sterol oleates and
      stearates on absorption and metabolism of cholesterol were compared in rats fed a
      cholesterol-supplemented diet. Fecal excretion of neutral steroids (cholesterol
      plus coprostanol) in rats fed unesterified plant sterols or plant sterol oleates
      was significantly higher than in those fed the control diet or plant sterol
      stearates. Deposition of cholesterol in the liver was significantly lower in rats
      fed unesterified plant sterols or plant sterol oleates than in those fed the
      control diet or plant sterol stearates. No significant difference was observed in
      fecal excretion of cholesterol plus coprostanol and hepatic cholesterol
      concentration between unesterified plant sterols and plant sterol oleates.
      Unesterified plant sterols were significantly more effective to reduce lymphatic
      recovery of radiolabeled cholesterol given to the stomach than plant sterol
      oleates. Although our observations suggest a possibility that unesterified plant
      sterols are potentially more effective to inhibit cholesterol absorption than
      plant sterol oleates in rats, difference in the activity is substantially small
      between these two forms of plant sterols.

PMID- 18635908
TI  - Preferential fat intake of pups nursed by dams fed low fat diet during pregnancy
      and lactation is higher than that of pups nursed by dams fed control diet and
      high fat diet.
AB  - To investigate the effect of dams' dietary fat type during pregnancy and
      lactation on fat choice of pups, three groups of dams were fed one of three
      diets: a low fat diet (LFD), a control diet (CTD) or a high fat diet (HFD). After
      weaning their pups were offered a self-selection regimen of both a fat protein
      diet (FPD) and a carbohydrate protein diet (CPD) for 3 wk. Although the ratio of
      FPD intake [FPD intake (g)/total intake (g)] by pups nursed by dams fed LFD
      during the self-selection period was higher than that by pups nursed by dams fed
      CTD and HFD, no significant difference in the ratio was observed between pups
      nursed by dams fed CTD and HFD. It was considered that pups nursed by dams fed
      CTD and HFD self-selected FPD and CPD in an adequate fat energy ratio (F ratio)
      compared to that of AIN-93G and AIN-93M. The ratio of FPD intake by pups of these
      three groups was 16-21% within the first week after weaning. Although pups nursed
      by dams fed CTD continued to consume the same ratio of FPD during the self
      selection period, the ratio of pups nursed by dams fed LFD increased and that of
      pups nursed by dams fed HFD decreased. These findings indicate that: [1] pups
      nursed by dams fed CTD and HFD have the ability to consume FPD and CPD in an
      adequate F ratio, and [2] preferential fat intake of pups nursed by dams fed LFD
      is stronger than that of pups nursed by dams fed CTD and HFD.

PMID- 18635909
TI  - Urinary water-soluble vitamins and their metabolite contents as nutritional
      markers for evaluating vitamin intakes in young Japanese women.
AB  - Little information is available to estimate water-soluble vitamin intakes from
      urinary vitamins and their metabolite contents as possible nutritional markers.
      Determination of the relationships between the oral dose and urinary excretion of
      water-soluble vitamins in human subjects contributes to finding valid nutrition
      markers of water-soluble vitamin intakes. Six female Japanese college students
      were given a standard Japanese diet in the first week, the same diet with a
      synthesized water-soluble vitamin mixture as a diet with approximately onefold
      vitamin mixture based on Dietary Reference Intakes (DRIs) for Japanese in the
      second week, with a threefold vitamin mixture in the third week, and a sixfold
      mixture in the fourth week. Water-soluble vitamins and their metabolites were
      measured in the 24-h urine collected each week. All urinary vitamins and their
      metabolite levels except vitamin B(12) increased linearly in a dose-dependent
      manner, and highly correlated with vitamin intake (r=0.959 for vitamin B(1),
      r=0.927 for vitamin B(2), r=0.965 for vitamin B(6), r=0.957 for niacin, r=0.934
      for pantothenic acid, r=0.907 for folic acid, r=0.962 for biotin, and r=0.952 for
      vitamin C). These results suggest that measuring urinary water-soluble vitamins
      and their metabolite levels can be used as good nutritional markers for assessing
      vitamin intakes.

PMID- 18635910
TI  - Effects of herring roe on plasma lipid, glucose, insulin and adiponectin levels,
      and hepatic lipid contents in mice.
AB  - We previously reported that lipids extracted from salted herring roe product
      (Kazunoko), which contains large amounts of cholesterol, phosphatidylcholine and
      n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA, 20:5n
      3) and docosahexaenoic acid (DHA, 22:6n-3), decreased plasma lipid and glucose
      concentrations in mice. The aim of this study was to evaluate the effects of
      Kazunoko containing large amounts of protein on lipid and glucose metabolism in
      mice. Male Crlj:CD-1 (ICR) mice were fed three experimental diets containing
      lyophilized Kazunoko for 12 wk. The experimental diets were as follows: without
      Kazunoko (control diet); 1% Kazunoko (1% Kazunoko diet); and 4% Kazunoko (4%
      Kazunoko diet). Plasma total cholesterol, phospholipid and glucose concentrations
      tended to be lower in the 1% and 4% Kazunoko diet groups than in the control diet
      group. There were significant differences in plasma glucose concentration between
      the control and 4% Kazunoko diet groups (p<0.05). Plasma adiponectin
      concentrations in mice fed the 4% Kazunoko diet were also significantly higher
      than in those fed the control diet (p<0.05), but there were no marked differences
      in plasma insulin concentration among the three dietary groups. Hepatic total
      cholesterol and phospholipid contents tended to be lower in the 4% Kazunoko diet
      group than in control diet group. Plasma and hepatic n-3/n-6 ratios in the 1%
      Kazunoko diet and 4% Kazunoko diet groups were significantly higher when compared
      with those of the control diet group (p<0.005 and p<0.0005, respectively). These
      results suggest that ingestion of Kazunoko influences lipid and glucose
      metabolism in mice fed the Kazunoko diets, as compared with animals fed the
      control diet.

PMID- 18635911
TI  - Role of low protein and low phosphorus diet in the progression of chronic kidney
      disease in uremic rats.
AB  - Restriction of dietary protein is useful for chronic kidney disease (CKD)
      patients to protect residual renal function. However, the mechanism by which a
      low protein diet confers a beneficial effect in CKD patients remains unknown. One
      possibility is that the benefit from a low protein diet is associated with
      phosphorus restriction. The aim of this study is to compare the effect of protein
      and phosphorus on the progression of renal insufficiency using irreversible Thy1
      rats, which histopathologically resemble IgA nephropathy. Irreversible Thy1 rats
      were fed six types of isocaloric diets consisting of three levels of protein
      (16.9, 12.6, and 8.4%) and two levels of phosphorus (0.5 and 0.3%) for 13 wk.
      Renal function was assessed biochemically and histopathologically. The low
      phosphorus (0.3%) diets showed protection of residual renal function regardless
      of dietary protein content in uremic rats. With the normal phosphorus (0.5%)
      diets, however, only the very low protein (8.4%) diet showed a beneficial effect,
      indicating that dietary phosphorus is a more important factor that affects the
      progression of renal insufficiency than dietary protein in this model.
      Furthermore, the low phosphorus diet also prevented an increase in serum
      parathyroid hormone, indicating that a low phosphorus diet might have beneficial
      effects not only for residual renal function but also for renal osteodystrophy, a
      typical complication of patients with CKD.

PMID- 18635912
TI  - Effect of the combination of ginseng, oriental bezoar and glycyrrhiza on
      autonomic nervous activity and immune system under mental arithmetic stress.
AB  - BACKGROUND: Stress reduces physical and mental tolerances (immune potential) of
      humans and it induces progression of existing illness or causes latent disorders
      to become active. Thus, the control and suppression of stress plays an important
      role in the improvement of quality of life and prevention of diseases. Ginseng,
      oriental bezoar and glycyrrhiza have been used for Kampo (herbal treatment) for
      thousand years and a number of pharmacological and clinical studies have reported
      their effects. However, it has not been previously described how the combination
      of these most commonly used herbs affect mental stress. OBJECTIVE: This is a
      randomized, double-blind, placebo-controlled experiment to examine the
      effectiveness of reducing stress response by taking Kampo. Ten healthy males
      (mean age 27+/-1) participated in the study. The effectiveness of stress
      reduction was assessed by measuring ECG, salivary chromogranin A (CgA), blood
      glucose, WBC, granulocytes, lymphocytes, NK cell activity, etc. Salivary and
      blood measurement values of pre- and post-mental arithmetic stress were compared.
      In addition, ECG measurement values of pre- and mid-mental arithmetic stress were
      compared. RESULTS: we observed a higher HF power and a lower SNS index, HR, CgA,
      WBC and granulocytes in the Kampo trial than those in the placebo trial. The HR,
      HF power and SNS index were changed significantly (p<0.05) and CgA, WBC and
      granulocytes tended to show some differences between the two trials (p<0.1).
      However, blood glucose, lymphocytes, and NK cell activity showed no significant
      differences between the Kampo and placebo trials. CONCLUSIONS: The result
      suggests that the Kampo should be useful in reducing mental stress.

PMID- 18635913
TI  - Bioactive substance from Grifola frondosa (maitake) mushroom inhibits CCAAT
      enhancer binding protein beta and delta expression on C3H10T1/2 B2C1 adipocyte
      cells.
AB  - Bioactive compound substances from Grifola frondosa (maitake) inhibited adipocyte
      differentiation of B(2)C(1) preadipocytes. This compound is not related to MAP
      kinase (ERK1 and ERK2) cascades or beta-catenin, which inhibit the expression of
      Glut4, PPARgamma and C/EBPalpha. The compound reduced the expression time of
      C/EBPbeta and C/EBPdelta. These results suggest that the inhibitory action of
      these bioactive compounds on adipocyte differentiation is exhibited through
      preadipocytes. They cannot induce the expression of PPARgamma or C/EBPalpha
      because of the reduced expression time of C/EBPbeta and C/EBPdelta.

PMID- 18635914
TI  - Enzymatic phosphatidylation of thiamin, pantothenic acid, and their derivatives.
AB  - Phospholipase D from Streptomyces sp. was found to catalyze the transfer reaction
      of the dipalmitoylphosphatidyl residue from 1,2-dipalmitoyl-3-sn
      phosphatidylcholine to thiamin, pantothenic acid, and their derivatives in a
      biphasic system. The following phosphatidylated compounds were synthesized: 1,2
      dipalmitoyl-3-sn-phosphatidylthiamin, 1,2-dipalmitoyl-3-sn-phosphatidylthiamin
      propyl disulfide, 1,2-dipalmitoyl-3-sn-phosphatidylthiamin tetrahydrofurfuryl
      disulfide, 1,2-dipalmitoyl-3-sn-phosphatidylpantothenic acid, and 1,2-dipalmitoyl
      3-sn-phosphatidyl-pantothenyl ethyl ether.

PMID- 18635915
TI  - Supplementing vitamin B6 to a low vitamin B6 diet exaggerates UVB-induced skin
      tumorigenesis in DMBA-treated hairless mice.
AB  - 7,12-Dimethylbenz[a]anthracene (DMBA)-treated hairless mice exposed to UVB
      radiation were used to examine the effect of graded levels of vitamin B(6) [1, 7
      or 35 mg pyridoxine (PN) HCl/kg] on skin tumorigenesis for 18 wk. Compared to the
      1 mg PN HCl/kg diet, the 35 mg PN HCl/kg diet significantly elevated the
      incidence and multiplicity of skin tumors, while there was no difference in skin
      tumorigenesis between the 7 and 35 mg PN HCl/kg diets. Skin levels of oxidative
      stress markers (lipid peroxides and protein carbonyls) were unaffected by dietary
      treatment. Compared to the 1 mg PN HCl/kg diet, the 7 and 35 mg PN HCl/kg diets
      significantly elevated serum pyridoxal 5'-phosphate (PLP) without affecting the
      skin level of PLP. The results suggest that dietary supplemental vitamin B(6)
      exaggerates UVB-induced skin tumorigenesis in hairless mice without affecting
      oxidative stress in the skin.

PMID- 18635916
TI  - Effect of corosolic acid on the hydrolysis of disaccharides.
AB  - The banaba leaf (Lagerstroemia speciosa L.) has been used in traditional Oriental
      medicine to treat diabetes in the Philippines. It contains corosolic acid (CA), a
      compound which has a hypoglycemic effect. We examined the effect of CA on blood
      glucose levels and the hydrolysis of disaccharides in the small intestine in
      mice. CA (10 mg/kg body weight) improved hyperglycemia after an oral
      administration of sucrose, and significantly reduced the hydrolysis of sucrose in
      the small intestine. These results suggest that the hypoglycemic activity of CA
      is derived, at least in part, due to the inhibition of the hydrolysis of sucrose.

PMID- 18635917
TI  - The electrophysiological properties of the mucosal barrier in the injured mouse
      jejunum in Ussing chambers.
AB  - We previously suggested in the in vitro mouse jejunum that when the primary
      epithelial barrier on the villi was largely disabled, a secondary mucosal barrier
      substitutes for the primary one. This study showed that the mucosal Ca(2+)
      removal did not further deteriorate the histology but increased transmural
      conductance and lucifer yellow flux, and decreased forskolin-induced potential
      difference. It is suggested that in this injury model the postulated secondary
      barrier is Ca(2+)-dependent and likely to be present on or immediately beneath
      the mucosal surface.

PMID- 18635918
TI  - Ranirestat (AS-3201), a potent aldose reductase inhibitor, reduces sorbitol
      levels and improves motor nerve conduction velocity in streptozotocin-diabetic
      rats.
AB  - Ranirestat (AS-3201) is a novel aldose reductase (AR) inhibitor with potentially
      beneficial effects on diabetic sensorimotor polyneuropathy. In this study, we
      performed a kinetic analysis to determine the mode of inhibition of ranirestat on
      AR and investigated the effects of ranirestat on sorbitol levels in the sciatic
      nerves and lens of streptozotocin (STZ)-diabetic rats. We also evaluated the
      effects on motor nerve conduction velocity (MNCV) in STZ-diabetic rats. Kinetic
      analyses revealed that the ranirestat inhibition of AR is uncompetitive and
      reversible. In the sciatic nerve and lens of STZ-diabetic rats, single oral
      administration of ranirestat slightly reduced sorbitol levels. However, repeated
      oral administration of ranirestat for 5, 21, or 60 days enhanced the reducing
      effect of the ranirestat on sorbitol levels in the sciatic nerves and lens of STZ
      diabetic rats with maximum effects after 21 days of treatment. Finally, repeated
      oral administration of ranirestat for 21 or 42 days dose-dependently improved the
      STZ-induced decrease in MNCV in STZ-diabetic rats. These findings demonstrate
      that repeated oral administration of ranirestat reduces sorbitol accumulation and
      improves MNCV in STZ-diabetic rats, indicating that ranirestat is an agent for
      the management of diabetic sensorimotor polyneuropathy.

PMID- 18635919
TI  - Inhibition of insulin-like growth factor 1 receptor signaling enhanced silibinin
      induced activation of death receptor and mitochondrial apoptotic pathways in
      human breast cancer MCF-7 cells.
AB  - Silibinin, which had been used as a hepatoprotectant, was shown to have
      anticancer activity. In this study we investigated the mechanisms of silibinin
      induced apoptosis in human breast cancer MCF-7 cells. Expressions of Fas ligand
      (FasL), Fas-associated death domain protein (FADD), and Bax were significantly up
      regulated in silibinin-treated cells, whilst silibinin induced a conspicuous
      translocation of Bax to mitochondria and release of cytochrome c to the cytosol.
      Therefore, both the extrinsic Fas death receptor and intrinsic mitochondrial
      death pathways played essential roles in silibinin-induced apoptosis. It was also
      found that silibinin markedly decreased protein expression of SIRT1, a mammalian
      homologue of yeast Sir2, which was proved to have a role in sequestering Bax away
      from mitochondria. Insulin-like growth factor 1 receptor (IGF-1R), a receptor
      tyrosine kinase with a crucial role in malignancy development, is expressed in
      most human primary breast carcinomas. Our results showed that silibinin-induced
      apoptosis was significantly reinforced by blocking IGF-1R signaling with
      tyrphostin AG1024, a specific inhibitor of IGF-1R autophosphorylation. Up
      regulation of FADD, down-regulation of SIRT1 expression, and activation of the
      mitochondrial death pathway were apparently enhanced by AG1024 in the silibinin
      treated MCF-7 cells.

PMID- 18635920
TI  - Bcl-2 family proteins were involved in pseudolaric acid B-induced autophagy in
      murine fibrosarcoma L929 cells.
AB  - Pseudolaric acid B (PAB) exerted cytostatic activity on murine fibrosarcoma L929
      cells. The cytostatic mechanism of PAB on L929 cells was investigated in this
      paper. At 36 h, after 80 microM PAB treatment, the inhibitory ratio was 65.37 +/-
      4.12%, and the MDC staining ratio was strongest in L929 cells. 3-Methyladenine (3
      MA), an inhibitor of autophagy, inhibited the generation of autolysosomes induced
      by PAB. The expression of autophagy-associated Beclin 1 protein was up-regulated,
      and microtubule-associated protein light chain 3 I (LC3 I) was cleaved into LC3
      II after 80 microM PAB treatment from 12 h. Therefore, it was concluded that PAB
      exerted a cytostatic effect on L929 cells through autophagy. However, 80 microM
      PAB treatment did not induce apoptotic body formation, but 3 mM 3-MA promoted
      apoptosis, so autophagy might inhibit apoptosis. PAB had no effect on
      mitochondrial membrane potential (MMP), but up-regulated the expressions of Bax
      and Bcl-2. Immunoprecipitation analysis showed that PAB inhibited Bcl-2 binding
      with Beclin 1. Additionally, PAB inhibited the localization of Bax in
      mitochondria, but Bcl-2 still was in the mitochondria to sustain MMP. Meanwhile
      PAB promoted the phosphorylation of cytoplasmic Bcl-2. Therefore the
      phosphorylation of Bcl-2 in the cytoplasm and the mitochondrial location of Bcl-2
      might be the reasons why PAB inhibited the binding of Bcl-2 and Beclin 1.

PMID- 18635921
TI  - N,N-Dimethyl-D-erythro-sphingosine inhibits store-operated Ca2+ entry in U937
      monocytes.
AB  - Calcium is a ubiquitous second messenger that controls a broad range of cellular
      functions, and store-operated calcium entry (SOCE) is the primary mechanism of
      regulated Ca(2+) entry in non-excitable immunocytes. In this study, we found that
      N,N-dimethyl-D-erythro-sphingosine (DMS) inhibited SOCE. In U937 cells, treatment
      with DMS for 2 h inhibited thapsigargin-induced SOCE by about 70%. DMS inhibited
      SOCE in a concentration-dependent manner when it was added to the cells after
      SOCE reached a plateau. DMS-induced SOCE inhibition was also confirmed by the
      Mn(2+)-quenching method, which monitors only Ca(2+) influx. Because sphingosine
      kinase inhibitors or protein kinase C (PKC) inhibitors could not mimic the SOCE
      inhibition, sphingosine kinase and PKC could be excluded as targets of DMS
      induced inhibition of SOCE. Furthermore, disruption of lipid rafts with methyl
      beta-cyclodextrin and bacterial sphingomyelinase did not influence DMS-induced
      inhibition of SOCE. DMS-induced inhibition of SOCE in U937 human monocytes is a
      unique observation and could serve as a basis to study modulation of
      intracellular Ca(2+) concentration by sphingolipids, although the precise
      mechanism should be elucidated in the future.

PMID- 18635922
TI  - Therapeutic effect of Siegesbeckia pubescens on cartilage protection in a rabbit
      collagenase-induced model of osteoarthritis.
AB  - Siegesbeckia pubescens (S. pubescens) was widely used to alleviate symptoms of
      osteoarthritis (OA) in traditional medicine. However, the mechanism of action of
      S. pubescens remains unresolved. In the present study, we determined the
      physiological relevance of S. pubescens on cartilage protection in collagenase
      induced osteoarthritis (CIA) in rabbits. The right knees of rabbits were injected
      intra-articularly with collagenase, and rabbits were orally administered with
      distilled water (vehicle), S. pubescens (100, 400 mg/kg) or celecoxib (100 mg/kg)
      once a day for 28 days after the initiation of the CIA. S. pubescens
      significantly suppressed the stiffness and global histological score including
      articular cartilage and synovial layer in CIA. Proteoglycan, aggrecan, and type
      II collagen expression was significantly increased in the rabbit knee joints of
      the S. pubescens-treated group. However, celecoxib had no effect on cartilage
      protection in CIA. The expression level of ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, and
      MMP-13 were dose-dependently decreased in the S. pubescens-treated group. In
      contrast, the level of TIMP-1 dose-dependently increased. The pro-inflammatory
      cytokines involved in cartilage destruction, such as IL-1beta, and inflammatory
      mediators containing PGE(2) and NO were also inhibited in the S. pubescens
      treated group. These results indicate that the cartilage protective effect of S.
      pubescens works through down-regulation of inflammatory mediators and
      aggrecanases and MMPs, while up-regulating TIMP-1 in the CIA rabbit model.

PMID- 18635923
TI  - Effects of cycloheximide on parthenogenetic development of pig oocytes activated
      by ultrasound treatment.
AB  - The present study was carried out to examine the parthenogenetic development of
      pig oocytes treated with different concentrations of cycloheximide for different
      durations following activation by ultrasound stimulation. When oocytes were
      treated with 10 microg/ml cycloheximide for different durations, the blastocyst
      formation rate of oocytes treated for 5 h was significantly (P<0.05) higher than
      those of oocytes treated for 0-2 h. The blastocyst formation rate of oocytes
      treated with 10 microg/ml cycloheximide for 5 h was significantly (P<0.05) higher
      than those of oocytes treated with 0-5 or 15-20 microg/ml cycloheximide for the
      same duration. When oocytes were treated with different concentrations of
      cycloheximide for 2 h, however, the blastocyst formation rate of oocytes treated
      with 40 microg/ml cycloheximide was significantly (P<0.05) higher than those of
      oocytes treated with 0-10 or 50 microg/ml cycloheximide. The blastocyst formation
      rate of oocytes treated with 10 microg/ml cycloheximide for 5 h was not
      significantly different from that of oocytes treated with 40 microg/ml
      cycloheximide for 2 h. These treatments did not affect the activation status of
      oocytes compared with controls that were not treated with cycloheximide. The
      results of the present study showed that cycloheximide improves the
      parthenogenetic development of pig oocytes activated by ultrasound stimulation.

PMID- 18635924
TI  - Interaction of estrogen and progesterone on kisspeptin-10-stimulated luteinizing
      hormone and growth hormone in ovariectomized cows.
AB  - BACKGROUND/AIMS: Growth hormone (GH) is necessary for optimal reproductive
      efficiency and its secretion is influenced by sex steroids. This study was
      designed to determine whether kisspeptin-10 (Kp10) could stimulate GH and if
      gonadal steroids enhance the GH response to Kp10 in cows. METHODS AND RESULTS:
      Intravenous injection of Kp10 at 100 or 200 pmol/kg body weight with or without
      treatment with estradiol cypionate and/or progesterone increased luteinizing
      hormone (p < 0.01) plasma concentrations. Plasma concentrations of GH were
      increased following Kp10 in cows treated with estradiol cypionate and/or
      progesterone (p < 0.05) but not in cows treated with Kp10 without gonadal
      steroids. CONCLUSIONS: These data suggest that reproductive steroids enhance the
      sensitivity of the somatotropic axis to physiologically relevant doses of Kp10,
      and support the possibility that Kp10 is an integrator of luteinizing hormone and
      GH release.

PMID- 18635925
TI  - Value of morning home blood pressure as a predictor of decline in renal function
      in patients with chronic kidney disease.
AB  - BACKGROUND: Although blood pressure (BP) control is significantly associated with
      progression of chronic kidney disease (CKD), the influence of BP control based on
      home BP (HBP) measurement on the change in renal function in CKD patients is not
      fully defined. METHODS: We recruited 137 patients with stage 3-5 CKD, who
      performed daily HBP measurements continuously. HBP was measured every morning and
      evening and data were obtained every 6 months in each patient with a follow-up of
      32 +/- 5 months. The associations between BP data, other clinical variables and
      the change in estimated glomerular filtration rate (eGFR) were examined. RESULTS:
      Mean morning BP, evening BP and clinic BP were 132.9/76.2, 128.5/72.5 and
      129.4/69.1 mm Hg, respectively. There were significant correlations between mean
      morning systolic BP (SBP), mean evening SBP, mean clinic SBP and the change in
      eGFR (r = -0.318, -0.215, -0.174, p < 0.0001, <0.05, <0.05). Stepwise
      multivariate regression analysis demonstrated mean morning SBP and mean urinary
      protein excretion as independent predictors of the change in eGFR. CONCLUSION:
      Morning SBP is a more significant predictor of decline in renal function than
      evening SBP or clinic SBP.

PMID- 18635926
TI  - Pulmonary hypertension in chronic renal failure patients.
AB  - BACKGROUND/AIMS: Pulmonary hypertension (PHT) has been reported to be high among
      end-stage renal disease (ESRD) patients. This study evaluated PHT in ESRD
      patients and the role of arteriovenous fistula (AVF), thromboxane B(2) (TXB(2))
      and pro-BNP in this complication. METHODS: 45 ESRD patients on regular
      hemodialysis (HD) (group 1) and 31 ESRD patients on conservative treatment (group
      2) underwent clinical and biochemical testing. Pulmonary artery pressure (PAP)
      was evaluated using Doppler echocardiography. Cardiac assessment by
      echocardiography and AVF flow measurement by Doppler ultrasound were done. Levels
      of TXB(2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in plasma were
      determined. RESULTS: PHT was found in 44.4% in group 1 and in 32.3% in group 2.
      Comparing the two groups shows a significant difference with regard to PAP,
      proBNP, and TXB(2). Patients with PHT have a significantly higher AVF blood flow,
      proBNP, and TXB(2). In patients with PHT, 76.7% have left ventricular diastolic
      dysfunction (LVDD). PAP correlates with AVF flow, proBNP, and TXB(2).
      CONCLUSIONS: Results show a high prevalence of PHT among patients with ESRD on
      chronic HD or on conservative treatment. PHT in such patients is related to AVF
      flow, TXB(2) and NT-proBNP level and LVDD. AVF flow is an important correctable
      cause of PHT.

PMID- 18635927
TI  - Renal parenchymal hypoxia, hypoxia response and the progression of chronic kidney
      disease.
AB  - Renal parenchymal hypoxia, documented under a variety of clinical conditions,
      conceivably contributes to the progression chronic kidney disease. In this
      review, normal physiologic medullary hypoxia and abnormal profiles of renal pO(2)
      in chronic kidney diseases are presented, and the mechanisms leading to anomalous
      renal tissue oxygenation are discussed. Direct measurements of pO(2) with oxygen
      electrodes, immunostaining with pimonidazole (which binds to regions with very
      low pO(2)), or the detection of hypoxia-inducible factor (HIF)-alpha (which
      accumulates in hypoxic regions, initiating hypoxia-adaptive responses), all serve
      to detect the distribution and extent of renal parenchymal hypoxia under
      experimental settings. The use of BOLD MRI as a noninvasive tool, detecting
      deoxygenated hemoglobin in hypoxic renal tissues, has evolved from experimental
      settings to human studies. All these modalities indicate that abnormal renal
      oxygenation develops under conditions such as chronic glomerular,
      tubulointerstitial or renovascular disease, in diabetes, hypertension, aging,
      renal hypertrophy, anemia or obstructive uropathy. Abnormal renal tissue hypoxia
      modifies the pattern of regional gene expression, evoking a host of adaptive and
      renoprotective pathways (such as HIF-mediated erythropoietin or heme-oxygenase
      1), in parallel with the induction of potentially harmful mediators that
      participate in the progression of chronic kidney injury. Slowing the progression
      of chronic kidney disease may be achieved by a better understanding of these
      parallel processes and the accomplishment of a selective control of such
      protective and maladaptive responses.

PMID- 18635928
TI  - Thalamic neurons in the pigeon compute distance-to-collision of an approaching
      surface.
AB  - The thalamofugal and tectofugal pathways in birds are two parallel visual
      pathways to the telencephalon and might be comparable to the geniculocortical and
      colliculo-pulvinar-cortical pathways in mammals, respectively. It is known that
      some tectal neurons in the tectofugal pathway can signal the time-to-collision of
      an approaching object. Here we show by single cell recording in the pigeon that a
      population of visual neurons in the nucleus opticus principalis thalami (nOPT) in
      the thalamofugal pathway is able to detect the distance-to-collision of a large
      surface approaching towards the animal. These neurons began response firing when
      the surface reached a threshold distance to the viewing eye and thereafter their
      firing rates increased exponentially until collision occurred at distance = zero.
      The response onset distance is nearly constant for a wide range of stimulus
      velocities and is equal to the product of velocity of approaching stimulus and
      response onset time of a nOPT cell. Furthermore, onset distance of looming
      responses in nOPT cells is close to that causing cardioacceleration in the pigeon
      viewing the approaching surface. It appears that nOPT and tectal neurons are
      dichotomized functionally to a large extent for detecting imminent dangers, and
      the pigeon's ability to compute the distance-to-collision of an approaching
      surface may benefit avoiding large obstacles during flight.

PMID- 18635930
TI  - Adenoviral gene therapy for pancreatic cancer: where do we stand?
AB  - BACKGROUND: The prognosis of patients with pancreatic cancer is poor. This is
      mainly caused by the late diagnosis, the aggressive biology and the lack of
      effective treatment modalities. Adenoviral gene therapy has the potential to
      selectively treat both primary tumor and (micro)metastatic tissue. METHODS: This
      review provides an overview of what has been achieved so far in the field of
      adenoviral gene therapy for pancreatic cancer. RESULTS: Transductional targeting
      allows decreased toxicity due to vector dissemination to non-target cells and
      permits delivery with a lower viral dose. It can evade or diminish the immune
      response, which remains a major problem. Transcriptional targeting evolves
      quickly but essential drawbacks such as the lack of an efficient animal model
      delay clinical application. Few clinical trials utilizing adenoviruses have been
      performed in patients with pancreatic cancer today. Worldwide, only seven phase
      III trials are being performed investigating adenoviral vectors in cancer
      patients. CONCLUSION: A clear therapeutic effect of adenoviral gene therapy in
      pancreatic cancer has not yet been achieved, because the step from bench to
      bedside has encountered drawbacks. Combinations of the different targeting
      strategies and techniques to evade the immune system harbor the future for
      adenoviral gene therapy in patients with pancreatic cancer.

PMID- 18635929
TI  - Characterization of the shark myelin Po protein.
AB  - Myelin, the insulating sheath made by extensive plasma membrane wrapping, is
      dependent on the presence of highly adhesive molecules that keep the two sides of
      the membrane in tight contact. The Po glycoprotein (Po) is the major component of
      the peripheral nervous system (PNS) myelin of mammals. The exact role that Po
      protein has played in the evolution of myelin is still unclear, but several
      phylogenetic observations suggest that it is a crucial component in the
      development of myelin as a multi-lamellar membrane structure. Sharks, which
      appeared in the fossil record about 400 million years ago, are the first fully
      myelinated organisms. In this study we investigated the expression pattern of
      shark myelin Po to suggest a way it might have played a role in the evolution of
      myelin in the central nervous system. We found that sharks have more than two
      isoforms (32, 28 and 25 kD), and that some of these might not be fully functional
      because they lack the domains known for Po homophilic adhesion.

PMID- 18635931
TI  - Malignant conjunctival tumors invading the orbit.
AB  - AIM: The aim of this study is to present the clinical and histopathological
      features as well as the treatment results of advanced conjunctival malignant
      tumors with orbital invasion, in the context of all secondary orbital tumors.
      METHODS: A total of 151 secondary orbital tumors were observed over a 10-year
      period; 21 (14%) out of 151 cases were detected to be of conjunctival origin, and
      the cases were reviewed retrospectively. The age, gender, duration of symptoms,
      clinical and histopathological features and the treatment results of patients
      were recorded. RESULTS: Four out of 21 patients had malignant melanoma (MM),
      while 17 had squamous cell carcinoma (SCC) of the conjunctiva. The mean duration
      of symptoms was 11.3 months in the MM and 18.5 months in the SCC group.
      Perineural invasion was detected in 1 of the MM and 3 of the SCC cases. The
      peritumorous inflammation score was higher in the SCC than the MM group (2.2 vs.
      1.5). Two patients underwent wide excision with control of the surgical margins
      and postoperative adjunctive topical chemotherapy. Nineteen patients needed
      exenteration. Two patients with regional metastasis were treated by radical neck
      dissection and radiation therapy to the neck. After a mean follow-up time of 35.6
      months, no tumor recurrence or tumor-related death was encountered. Seven
      patients died from non-tumor-related causes. CONCLUSION: Delay in presentation
      for treatment and previous unsuccessful surgery of conjunctival malignant lesions
      are likely to lead to orbital invasion and loss of the eye. Exenteration is
      generally needed but margin-controlled wide surgical excision and adjuvant
      chemotherapy may be curative in selected cases. Early diagnosis and effective
      treatment of lesions will minimize the mortality rate and morbidity related to
      the disease.

PMID- 18635932
TI  - Visual prognosis and risk factors for korean patients with behcet uveitis.
AB  - PURPOSE: Visual prognosis was evaluated in Korean Behcet uveitis patients. The
      study investigated factors associated with poor visual outcome, and the effect of
      various treatments on recurrence-free duration. METHODS: A retrospective analysis
      was undertaken on 99 consecutive Behcet uveitis patients (168 eyes). Visual
      prognosis was evaluated using Kaplan-Meier survival curves, and Cox's
      proportional hazard regression analysis was used to identify risk factors.
      RESULTS: Visual acuity at the first visit (<0.5), presence of vasculitis, male
      gender, and posterior/panuveitis type were associated with poor visual prognosis.
      Visual acuity at the first visit was found to be the most significant risk factor
      (hazard ratio = 7.392, p = 0.007). Analysis of 9 different treatment modalities
      showed patients treated with steroids had longer recurrence-free periods than
      those not treated with steroids (p = 0.0053, t test). CONCLUSION: Whilethe long
      term visual prognosis for Behcet uveitis may be affected by many factors, the
      initial visual acuity appears to be the most significant. Treatments involving
      steroids appear to decrease the frequency of uveitis recurrence.

PMID- 18635933
TI  - Correspondence between self-reported and parent-reported psychopathology in
      adolescents with eating disorders.
AB  - BACKGROUND: This study examined parent/youth self-report agreement on emotional
      and behavioral symptoms among adolescents with eating disorders (ED). SAMPLING
      AND METHODS: Eighty-three parent-adolescent pairs participated. All adolescents
      (age 11-18 years) were females and met diagnostic criteria according to the DSM
      IV for anorexia nervosa restricting type (n = 53) or bulimia nervosa (n = 30).
      Diagnoses were confirmed using the Structured Inventory for Anorectic and Bulimic
      Syndromes. Parents completed the Child Behaviour Checklist, and the adolescents
      completed the corresponding Youth Self-Report. RESULTS: Results of the interclass
      correlation provide very poor coefficients between parents and adolescents,
      especially for the internalizing subscale. Analyses of variance of repeated
      measures revealed significant differences in the total problem score and the
      internalizing subscore between parents and adolescents. Parents reported
      significantly more internalizing problems than adolescents. CONCLUSIONS:
      Agreement between parents and adolescents regarding the presence and severity of
      psychiatric symptoms in adolescents with ED is low. In contrast to previous
      studies in non-ED samples, adolescents with ED reported lower levels of
      internalizing problems than their parents. Denial and minimization may be
      underlying reasons for our findings and represent obstacles in the psychological
      assessment of adolescents with ED.

PMID- 18635934
TI  - Temperament and personality dimensions in suicidal and nonsuicidal psychiatric
      inpatients.
AB  - BACKGROUND: Suicide is a serious public health problem. In the international
      literature there is evidence to support the notion that certain temperaments and
      personality traits are often associated with suicidal behavior. SAMPLING AND
      METHODS: In this study, 150 psychiatric inpatients were investigated using the
      Temperament Evaluation of Memphis, Pisa, Paris and San Diego autoquestionnaire,
      the Minnesota Multiphasic Personality Inventory, 2nd edition (MMPI-2) and the
      Beck Hopelessness Scale and evaluated for suicide risk by means of the critical
      items of the Mini International Neuropsychiatric Interview. RESULTS: Statistical
      analysis, including logistic regression analysis and multiple regression
      analysis, showed that suicide risk contributed to the prediction of hopelessness.
      Among the temperaments, only the hyperthymic temperament, as a protective factor,
      and the dysthymic/cyclothymic/anxious temperament contributed significantly to
      the prediction of hopelessness. Irritable temperament and social introversion
      were predictive factors for suicidal risk. Hopelessness and depression were
      associated with higher suicidal behavior and ideation, but, unexpectedly,
      depression as measured by the MMPI did not contribute significantly to the
      multiple regressions. CONCLUSIONS: The present study indicated that, although
      suicidal psychiatric patients have MMPI-2 profiles in the pathological range,
      they exhibit several differences from nonsuicidal patients. Patients at risk of
      suicide have specific temperaments as well as personality and defense mechanism
      profiles. They are more socially introverted, depressed and psychasthenic, and
      use hysterical and schizoid mechanisms more often. Generalizability of the
      findings was limited by the small sample size and the mix of bipolar disorder I,
      bipolar disorder II, major depressive disorder and psychotic disorder patients.

PMID- 18635935
TI  - First-episode psychosis: diagnostic stability over one and two years.
AB  - BACKGROUND: Diagnostic stability is important for daily clinical work and
      planning of treatment. The aims of this study were to measure diagnostic
      stability in a clinical epidemiologic sample and to identify markers of change in
      diagnosis. SAMPLING AND METHODS: Diagnostic stability and change were measured in
      a sample of 301 patients with first-episode psychosis from four national health
      care sectors in Norway and Denmark at baseline, 1 and 2 years. RESULTS:
      Diagnostic stabilities were high for schizophrenia and schizoaffective disorder
      (85-99%), low for schizophreniform disorder (16-19%), and intermediate for other
      diagnoses. Diagnostic change from schizophreniform to schizophrenia was frequent
      in year 1 (72%). Characteristics discriminating schizophreniform patients keeping
      their diagnosis (i.e. having recovered within 6 months with no relapse) from
      those developing schizophrenia at 1 year were female gender, better childhood
      premorbid functioning, shorter duration of untreated psychosis and more severe
      general psychotic symptoms, especially excitation. CONCLUSIONS: Findings provide
      validation for the DSM-IV categories within the schizophrenic spectrum. The
      limitations of the study were: the raters were not blind to baseline assessments;
      patients with longer duration of untreated psychosis were more likely to refuse
      participation; not all patients were assessed at 1- and 2-year follow-up, but the
      attrition was rather low.

PMID- 18635936
TI  - Psychophysiological indicators of stress reactivity in adolescent psychiatric
      patients with dissociative symptomatology.
AB  - BACKGROUND: Thus far, possible neurobiological underpinnings of dissociative
      symptomatology have not been studied sufficiently. We studied the reactivity of
      the autonomous nervous system to a non-specific laboratory stressor in a clinical
      group of adolescents with dissociative symptomatology. SAMPLING AND METHODS: The
      effects of an attentional task, administered with and without noise, on heart
      rate, skin resistance and the level of subjective distress were studied in 2
      groups of 19 and 20 adolescent psychiatric patients with high and low degrees of
      self-reported dissociative symptoms as measured by the Adolescent Dissociative
      Experiences Scale, respectively. RESULTS: Patients with a high degree of
      dissociative symptoms demonstrated significantly larger changes in heart rate
      during the attentional task, while the noise had no effect on heart rate.
      Additional noise led to an increase in skin resistance levels and subjective
      distress in both groups. CONCLUSIONS: The results of the current study provide
      preliminary evidence that the intensity of the stress response represents a
      sensitivity to stress which may correlate with the exacerbation and fluctuation
      of dissociative symptomatology.

PMID- 18635937
TI  - Assessment of mood and affect by mental state examination in different cultural
      contexts.

PMID- 18635938
TI  - Nils Retterstol in memoriam (1924-2008).

PMID- 18635939
TI  - Adult precursor T-lymphoblastic leukemia/lymphoma with myeloid-associated antigen
      expression is associated with a lower complete remission rate following induction
      chemotherapy.
AB  - Prognostic studies of T-cell lymphoblastic leukemia/lymphoma (T-ALL) have been
      performed in small patient cohorts with conflicting results. We systematically
      reviewed 67 adult T-ALL patients diagnosed and treated at our institute to
      identify clinical and pathologic prognostic factors. The median initial WBC was
      21.3 x 10(9)/l. Blasts expressed at least one myeloid-associated antigen in 33%.
      Karyotypes were abnormal in 32% of the cases. Fifty-six of 64 patients (88%)
      achieved complete remission (CR). In univariate analysis, age, gender, initial
      WBC, CD10, CD34 and abnormal karyotype did not predict CR. Patients expressing at
      least one myeloid-associated antigen had a CR of 74% compared to 94% (p = 0.04)
      for those not expressing myeloid antigens. None of the above factors affected
      relapse-free or overall survival in this cohort. Our study indicates that
      expression of myeloid-associated antigens is associated with a lower CR rate in
      adult T-ALL and may be considered in risk stratification for induction
      chemotherapy.

PMID- 18635940
TI  - Asthma and gastroesophageal reflux: clinical evaluation of esophago-bronchial
      reflex and proximal reflux.
AB  - AIMS: To evaluate the prevalence of proximal reflux and esophago-bronchial reflex
      (EBR) in patients with asthma, and to compare the symptom spectrum, esophageal
      acid sensitivity, pH monitoring, and the endoscopic and manometric parameters of
      EBR-positive and -negative patients with asthma. PATIENTS AND METHODS: Forty
      three consecutive patients with recent diagnoses of asthma and 20 patients with
      chronic cough but without asthma were prospectively submitted to detailed reflux
      and respiratory symptom analysis, upper gastrointestinal endoscopy, esophageal
      manometry, Bernstein test and double-channel intra-esophageal pH monitoring. The
      presence of EBR was studied by combined esophageal acid (0.1 N HCl) perfusion and
      methacholine test. RESULTS: Patients with asthma had significantly more proximal
      acid reflux than controls. Patients with EBR positivity were more likely to have
      an acid-sensitive esophagus and had more acid reflux especially in the supine
      period at the distal measurement point. Other parameters were similar.
      CONCLUSIONS: Patients with asthma had significantly more proximal acid reflux
      than those with chronic cough. The combination of the methacholine test with
      esophageal acid perfusion is able to establish the presence of EBR, however
      prospective therapeutic trials are needed to confirm its clinical value. The
      increased amount of acid reflux during the supine period in patients with EBR may
      indicate a role for appropriate nighttime acid suppressive therapy.

PMID- 18635941
TI  - Time until institutionalization in incident dementia cases--results of the
      Leipzig Longitudinal Study of the Aged (LEILA 75+).
AB  - BACKGROUND: Information on the time until institutionalization and its predictors
      in demented subjects has so far been based on studies with selected samples or
      prevalent dementia cases. Thus, the aim of the study is to analyze the time until
      institutionalization and associated patient-related factors in incident dementia
      cases. METHODS: Data were derived from the Leipzig Longitudinal Study of the Aged
      (LEILA 75+), a population-based study of individuals aged 75 years and older.
      Kaplan-Meier survival analysis was used to determine the time until
      institutionalization. Factors associated with time until institutionalization
      were analyzed using Cox proportional hazards models. RESULTS: One hundred and
      nine subjects with incident dementia who resided in a private home setting at the
      time of the dementia diagnosis were identified. Fifty-two (47.7%) of these
      subjects had become residents of a nursing home by the end of the study. The
      median time until institutionalization was 1,005 days (95% CI = 808-1,202). Being
      widowed/divorced (compared to being married) was associated with a significantly
      shorter time until institutionalization (univariate model: HR = 4.50, 95% CI =
      1.09-18.57). CONCLUSION: Being without a spouse seems to be an important factor
      for a shorter time until institutionalization in incident dementia cases.
      Tailored interventions for these subjects at risk are required.

PMID- 18635942
TI  - Neurosignals. Editorial note.

PMID- 18635943
TI  - Imaging of molecular dynamics regulated by electrical activities in neural
      circuits and in synapses.
AB  - One of the major challenges in brain research is to unravel a network of
      molecules, neurons, circuits and systems that are responsible for dynamic and
      hierarchical brain functions. To understand molecular events that occur in
      synapses could be an important key to exploring the mechanism of information
      processing. A spatiotemporal recording method is required to observe neuronal
      activities in a particular local circuit and to resolve single synaptic potential
      with high resolution. As alternative methods, real-time imaging using fluorescent
      probes and optical recording methods are also a powerful approach for
      investigating the molecular dynamics of biological events in neurons in vitro and
      in vivo. Recently, optical imaging techniques have become of great importance to
      visualize the molecular dynamics in a micron-sized compartment of a single neuron
      such as neuronal synapse. In general, the presynaptic axon forms synapses at the
      postsynaptic site on the dendritic spines in the mammalian central nervous
      system. Subsets of the synapses undergo a series of enduring changes in spine
      shape and density as well as alterations in electrophysiological functions. Here
      we describe recent optical imaging studies conducted by elaborate methods and
      techniques that provide evidence for the link between neural activity and
      molecular dynamics.

PMID- 18635944
TI  - Neuron-astrocyte signaling in the development and plasticity of neural circuits.
AB  - Emerging evidence indicates that signaling between perisynaptic astrocytes and
      neurons at the tripartite synapse plays an important role during the critical
      period when neural circuits are formed and refined. Cross-talk between astrocytes
      and neurons during development mediates synaptogenesis, synapse elimination and
      structural plasticity through a variety of secreted and contact-dependent
      signals. Recent live imaging studies reveal a dynamic and cooperative interplay
      between astrocytes and neurons at synapses that is guided by a variety of
      molecular cues. A unifying theme from these recent findings is that astrocytes
      can promote the development and plasticity of synaptic circuits. Insight into the
      molecular mechanisms by which astrocytes regulate the wiring of the brain during
      development could lead to new therapeutic strategies to promote repair and
      rewiring of neural circuits in the mature brain following CNS injury and
      neurodegenerative disease.

PMID- 18635945
TI  - Targeted optical probing of neuronal circuit dynamics using fluorescent protein
      sensors.
AB  - Interest in non-invasive methods for optical probing of neuronal electrical
      activity has been ongoing for several decades and methods for imaging the
      activity of single or multiple individual neurons in networks composed of
      thousands of neurons have been developed. Most widely used are techniques that
      use organic chemistry-based dyes as indicators of calcium and membrane potential.
      More recently a new generation of probes, genetically encoded fluorescent protein
      sensors, have emerged for use by physiologists studying the operation of neuronal
      circuits. In this review we describe the advance of these emerging optical
      techniques and compare them with more conventional approaches.

PMID- 18635946
TI  - Systems biology perspectives on cerebellar long-term depression.
AB  - Long-term depression (LTD) at parallel fiber-Purkinje cell (PF-PC) synapses is
      thought to be the cellular correlate of cerebellar associative learning. The
      molecular processes are, in brief, phosphorylation of AMPA-type glutamate
      receptors (AMPARs) and their subsequent removal from the surface of the PF-PC
      synapse. In order to elucidate the fundamental mechanisms for cerebellar LTD and
      further the understanding of its computational role, we have investigated its
      systems biology and proposed the following hypotheses, some of which have already
      been experimentally verified: (1) due to the mitogen-activated protein kinase
      (MAPK)-protein kinase C (PKC) positive feedback loop, phosphorylation of AMPARs
      is an all-or-none event; (2) the inositol 1,4,5-triphosphate receptor detects
      concurrent PF and climbing fiber inputs, forming the cellular basis for
      associative learning, and (3) the local concentration of nitric oxide in the PC
      dendrite reflects the relevance of a given context, enabling context-dependent
      selection of learning modules within the cerebellum. In this review, we first
      introduce theoretical studies on cerebellar LTD, mainly focusing on our own
      published work, followed by a discussion of the effects of stochasticity,
      localization, diffusion, and scaffolding. Neurons embody two features that are
      apparently contradictory, yet necessary for synaptic memory: stability and
      plasticity. We will also present models for explaining how neurons solve this
      dilemma. In the final section, we propose a conceptual model in which a cascade
      of excitable dynamics with different time scales, i.e., Ca(2+)-induced Ca(2+)
      release, the MAPK-PKC positive feedback loop, and protein kinase Mzeta (PKMzeta)
      induced PKMzeta synthesis, provides a mechanism for stable memory that is still
      amenable to modifications.

PMID- 18635947
TI  - FKBP family proteins: immunophilins with versatile biological functions.
AB  - Immunophilins consist of a family of highly conserved proteins binding with
      immunosuppressive drugs such as FK506, rapamycin and cyclosporin A. FK506-binding
      protein (FKBP) is one of two major immunophilins and most of FKBP family members
      bind FK506 and show peptidylprolyl cis/trans isomerase (PPIase) activity. Small
      size FKBP family members contain only FK506-binding domain, while FKBPs with
      large molecular weights possess extra domains such as tetratricopeptide repeat
      domains, calmodulin binding and transmembrane motifs. FKBPs are involved in
      several biochemical processes including protein folding, receptor signaling,
      protein trafficking and transcription. FKBP family proteins play important
      functional roles in the T-cell activation, when complexed with their ligands. The
      roles of immunophilins in protein transportation and apoptosis through their
      molecular interactions with receptors or proteins have emerged recently.
      Moreover, therapeutic implications of immunophilin ligands in treating
      neurodegenerative disorders have been accumulating. FK506 and its derivatives
      with no immunosuppressive activities bind to the conserved active sites of the
      canonical FKBP members such as FKBP12, which shows PPIase activity. These
      immunophilin ligands show variable efficacy in animal models for Parkinson's
      disease, dementia, and spinal cord injury, where the canonical immunophilins
      function as chaperones and are associate with the protein folding and modulation
      of oxidative stress. On the other hand, in the noncanonical FKBP members such as
      FKBP38, FK506-binding site is not conserved and shows neither PPIase activity nor
      affinity to FK506. Interestingly, the small molecule-mediated inhibition of the
      noncanonical member of FKBP family appears to cause neuronal protection and
      induce proliferation of neuronal stem cells in a rat focal cerebral ischemia
      model. Currently, the mechanisms of actions remain unclear. This review focuses
      on molecular characteristics of the canonical and noncanonical FKBP family
      members and the biological functions of their ligands in performing
      neuroprotective and neurotrophic activities.

PMID- 18635948
TI  - Mucolipidosis type IV: the importance of functional lysosomes for efficient
      autophagy.
AB  - Mucolipidosis IV (MLIV) is a lysosomal storage disorder characterized by severe
      neurological and ophthalmologic abnormalities. In contrast with most lysosomal
      storage disorders, which are attributed to the absence of specific lysosomal
      hydrolases, accumulation of material in MLIV results from defects in membrane
      transport along the late endocytic pathway. Mutations in MCOLN1 are the cause of
      MLIV; however, how the lack of MCOLN1 function ultimately leads to
      neurodegeneration remains largely unknown. We found that MCOLN1 is required for
      efficient fusion of both late endosomes and autophagosomes with lysosomes.
      Impaired autophagosome degradation results in accumulation of autophagosomes in
      MLIV fibroblasts. In addition, we found increased levels and aggregation of p62,
      suggesting that abnormal accumulation of ubiquitinated protein inclusions may
      contribute to the neurodegenerative phenotype observed in MLIV patients. These
      findings corroborate recent evidence indicating that defects in autophagy may be
      a common feature of many neurodegenerative disorders.

PMID- 18635949
TI  - Insights into links between familial and sporadic Parkinson's disease: physical
      relationship between UCH-L1 variants and chaperone-mediated autophagy.
AB  - Ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed abundantly in neurons and
      has been reported to be a major target of oxidative/carbonyl damage associated
      with sporadic Parkinson's disease (PD). The I93M mutation in UCH-L1 is also
      associated with familial PD. We recently reported that UCH-L1 physically
      interacts with LAMP-2A, the lysosomal receptor for chaperone-mediated autophagy
      (CMA), and Hsc70 and Hsp90, both of which can function as components of the CMA
      pathway. We found that the levels of these interactions were aberrantly increased
      by the I93M mutation, and that expression of I93M UCH-L1 in cells induced the CMA
      inhibition-associated increase in the amount of alpha-synuclein, a risk factor
      for PD. The interactions of UCH-L1 with LAMP-2A, Hsc70 and Hsp90 were also
      abnormally enhanced by carbonyl modification of UCH-L1. We propose that aberrant
      interactions of UCH-L1 variants with CMA machinery, at least partly, underlie the
      pathogenesis of I93M UCH-L1-associated PD, and possibly of sporadic PD. Our
      findings may provide novel insights into the links between familial and sporadic
      PD.

PMID- 18635950
TI  - Perturbation of autophagic pathway by hepatitis C virus.
AB  - Autophagy removes long-lived proteins and damaged organelles and is important for
      maintaining cellular homeostasis. It can also serve in innate immunity to remove
      intracellular pathogens. As such, viruses have evolved different mechanisms to
      subvert this innate immune response. We have recently demonstrated that hepatitis
      C virus (HCV) can also suppress autophagic protein degradation by suppressing the
      fusion between autophagosomes and lysosomes. This suppression causes the
      accumulation of autophagosomes and enhances HCV RNA replication.(1) Our further
      analysis indicated that the induction of autophagosomes by HCV is dependent on
      the unfolded protein response (UPR). Our studies thus delineate a molecular
      pathway by which HCV induces autophagosomes. The prolonged perturbation of the
      autophagic pathway by HCV likely plays an important role in HCV pathogenesis.

PMID- 18635951
TI  - Targeting intercellular signals for bone regeneration from bone marrow
      mesenchymal progenitors.
AB  - There are tremendous unmet clinical needs for effective strategies to enhance
      bone regeneration in vivo. The sustained presence of multipotent mesenchymal
      progenitors in the bone marrow in aged and osteoporotic individuals offers the
      potential for therapeutic interventions to induce osteoblast production from the
      resident progenitors. Recent advances in understanding the intercellular signals
      governing osteogenic decisions may provide targets for developing novel bone
      enhancing therapeutics.

PMID- 18635952
TI  - Mitotic regulation of SREBP and ATF6 by separation of the Golgi and ER.
AB  - The highly organized structure of the Golgi apparatus becomes compromised during
      mitosis. The Golgi cisternae unstack and form vesicles, which are then
      partitioned into the daughter cells. Here, we analyzed the fate of the SREBP and
      ATF6, two key transcription factors of sterol biogenesis and the unfolded protein
      response, respectively. During interphase the precursors of both transcription
      factors are silent in the ER, but upon activation signals SREBP and ATF6 move to
      the Golgi where they are activated by proteolytic cleavage by S1P and S2P. Since
      the spatial separation between the ER and the Golgi is the basis for the
      regulated activation, we investigated whether mitosis is sufficient to trigger
      activation. We found that the strict compartmentalization of the ER and the Golgi
      is maintained during mitosis to inhibit the activation of SREBP and ATF6.

PMID- 18635953
TI  - Finding an "Achilles' heel" of cancer: the role of glucose and glutamine
      metabolism in the survival of transformed cells.
AB  - Multiple lines of evidence indicate that the process of tumorigenesis is often
      associated with altered metabolism of two major nutrients, glucose and glutamine.
      These two nutrients are engaged in multiple metabolic pathways that can be
      required for cell viability. The roles of glucose and glutamine in the survival
      of transformed cells both in vitro and in vivo have been separately evaluated in
      various cell systems, and glucose as the major cellular energy source has
      received most of the attention. At the same time, data suggests that the
      inclusion of glucose and glutamine into specific metabolic pathways and cellular
      sensitivity to the availability of either of these nutrients depends on the cell
      origin and the combination and nature of transforming events. Exploiting cell
      metabolism to develop selective cancer therapeutics requires consideration of
      these factors and evaluation of the requirement of glucose and glutamine
      metabolism for survival of different transformed cells. Here we discuss possible
      molecular mechanisms underlying oncogene-induced sensitivity to deprivation of
      these nutrients.

PMID- 18635954
TI  - A wide-ranging cellular response to UV damage of DNA.
AB  - The kinases ATM and ATR are central to proper function of the DNA damage
      response. These kinases phosphorylate proteins to coordinate cell cycle
      progression and DNA damage repair/bypass. We have recently reported a large-scale
      identification of ATM/ATR substrates phosphorylated in response to UV damage of
      DNA. Overall 231 sites of phosphorylation were induced by UV damage of DNA or
      dependent on proper function of ATR. The study expanded the number of
      phosphorylation sites from protein classes known to be involved in the DNA damage
      response. Further, many sites were identified from protein types not thought to
      have a role in damage signaling. This observation suggests that the DNA damage
      response affects a much wider range of cellular processes than was previously
      appreciated. This study has also extended the successful use of the PhosphoScan
      proteomic method from phospho-tyrosine to serine/threonine motifs, providing a
      general blueprint to use the method to study signaling pathways underlying a wide
      range of diseases.

PMID- 18635955
TI  - Cell cycle regulation in hair cell development and regeneration in the mouse
      cochlea.
AB  - Cell cycle inhibitors play important roles in the development of mammalian
      cochleae. Loss of function of those factors in mice at various developmental
      stages results in distinct phenotypes characterized by overproduction or loss of
      cochlear sensory cells. Our recent study showed that acute deletion of the
      retinoblastoma protein (Rb) induces rapid cell cycle reentry and subsequent loss
      of postnatal cochlear hair cells in mice. Clearly, these regulators play multiple
      roles in cell cycle exit and differentiation of hair cell and supporting cell
      progenitors. They are also crucial in maintenance of postmitotic states and
      survival of differentiated hair cells and supporting cells. In mammals, lost hair
      cells cannot be spontaneously replaced, leading to permanent deafness. However,
      lower vertebrates such as birds and fish can naturally regenerate damaged hair
      cells from the underlying supporting cells through proliferation and
      transdifferentiation. Thus, manipulating cell cycle inhibitors in mammalian
      cochleae could provide a new avenue to restore hearing in deaf people caused by a
      variety of genetic mutations and environmental insults.

PMID- 18635956
TI  - Systems biology of mammalian cell division.
AB  - High-throughput screening technologies allow the identification of genes and
      proteins essential for mammalian cell division. However, the underlying
      complexity and connectivity of different biological processes, such as signal
      transduction, transcription, translation and proteolysis make it difficult to
      understand the mammalian cell cycle based on the analysis of its individual
      components alone. The recent development of robust and precise assays to study
      the mammalian cell cycle, in combination with functional genomics and proteomics,
      together provide the necessary tools to address this critical issue. With the
      implementation of different "Omics" technologies for quantitative and high
      throughput data acquisition, the possibility of obtaining a more detailed view of
      the mammalian cell cycle is now realistic. Here, we review RNAi reagents, assays
      and validation strategies for the identification of genes functioning in the
      human cell cycle, and outline genomic, proteomic and microscopic approaches to
      further characterize their specific functions. While a fully integrated model of
      mammalian cell division remains a distant goal, a framework of a systems
      understanding of this medically relevant process is beginning to emerge.

PMID- 18635957
TI  - The XS domain of a plant specific SGS3 protein adopts a unique RNA recognition
      motif (RRM) fold.
AB  - RNA interference (RNAi) is a unique gene regulation mechanism in eukaryotic
      organisms. It is typically mediated by short interfering RNAs (siRNAs), microRNAs
      (miRNAs), and recently discovered PIWI-interacting RNAs (piRNAs). In plants, RNAi
      is also called post-transcriptional gene silencing (PTGS), in which diverse small
      RNAs are utilized to defend against viral or bacterial infection, and to modulate
      endogenous gene expression and chromatin structure. Many PTGS-related genes have
      been identified by genetic screens in plants, including suppressor of gene
      silencing 2 (SGS2, also called RDR6), SGS3, hua enhancer 1 (HEN1), dicer-like 4
      (DCL4), and argonaute 1 (AGO1). For most of these proteins, their potential
      functions have been uncovered through sequence similarity searches and protein
      domain examinations. For instance, SGS2 encodes a RNA-dependent RNA polymerase
      (RdRp); HEN1 is a RNA methyltransferase with a double-stranded RNA-binding motif;
      DCL4 is a Dicer for producing siRNAs; and AGO1 is a RNA slicer with PIWI and PAZ
      domains. Their retrieved homologs in other organisms including mammals,
      Drosophila and the nematode Caenorhabditis elegans have also been shown to be
      crucial in RNAi pathways, indicating an evolutionary conservation for RNAi
      mechanisms. However, one exception is the SGS3 protein, whose specific function
      remains unclear so far.

PMID- 18635958
TI  - Effects of anti-microtubule agents on microtubule organization in cells lacking
      the kinesin-13 MCAK.
AB  - Dynamic microtubules are necessary for proper mitotic spindle assembly and
      chromosome segregation during mitosis. Members of the kinesin superfamily of
      molecular motor proteins are important to spindle function. Of particular
      interest is the Kinesin-13 family member MCAK, which acts to regulate microtubule
      dynamics during spindle assembly and to ensure proper attachments of chromosomes
      to spindle microtubules. The unique ability of MCAK to regulate microtubule
      dynamics makes it a potential target for development of new drugs that alter
      spindle function. Here, we knocked down MCAK via RNAi in normal and malignant
      cell lines and found that the two tested malignant cell lines were acutely
      sensitive to MCAK knockdown, while the tested normal cells were less sensitive.
      In addition, we looked at the effect of combining MCAK knockdown and drug
      treatment with paclitaxel or vinblastine to identify spindle assembly defects. We
      found that MCAK knockdown increased the morphological defects of the microtubule
      cytoskeleton in HeLa cells caused by anti-microtubule drugs. Our studies support
      the idea that MCAK would be a good target for new chemotherapeutic development
      and may be particularly useful in combination therapies with currently available
      anti-microtubule agents.

PMID- 18635959
TI  - Akt and mRNA translation by interferons.
AB  - The important antiviral and antitumor properties of interferons (IFNs) in vitro
      and in vivo have triggered extensive investigations over the years to understand
      the signals that control such responses in normal and malignant cells. The
      discovery of IFN-regulated Jak-Stat pathways and various ancillary cascades has
      led to the definition and establishment of models by which early signals at the
      IFN receptor level ultimately induce transcription of IFN-controlled genes to
      generate antiviral and antitumor responses. An important outstanding issue in the
      field has been the identification of the mechanisms responsible for regulation of
      mRNA translation of IFN-sensitive genes. There is emerging evidence suggesting
      that mTOR and its effectors play key and essential roles in the generation of
      such responses. Moreover, recent studies point towards Akt as a common and
      central integrator for such responses in Type I and II IFN signaling, via its
      regulatory effects on mTOR. Here, we review the accumulating evidence on the
      importance of Akt in IFN-signaling, with particular emphasis on its role in mRNA
      translation of IFN-sensitive genes. The implications of such studies on the
      overall perception of the Akt pathway are also discussed.

PMID- 18635960
TI  - TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in
      metastasis and development.
AB  - Hypoxia is a microenvironmental factor which plays a critical role in development
      and tumor progression. The hypoxic response is mainly mediated by hypoxia
      inducible factor-1 (HIF-1) composed of HIF-1alpha and HIF-1beta, which becomes
      active under low oxygen condition. HIF-1 activates the transcription of hypoxia
      inducible genes which regulate diverse cellular functions including metabolism,
      angiogenesis and invasion. In cancer metastasis, HIF-1-regulated genes promote
      angiogenesis, invasion and epithelial-mesenchymal transition (EMT), a critical
      step of metastasis. TWIST is a master regulator of gastrulation and mesoderm
      specification and is recently implicated to be essential to mediate cancer
      metastasis. We recently showed that HIF-1 promotes EMT through direct regulation
      of TWIST expression. TWIST is critical for hypoxia mediated EMT and metastasis.
      TWIST plays a non-redundant role in relation to other EMT regulators (e.g.,
      Snail) under hypoxia. Co-expression of HIF-1alpha, TWIST and Snail could be used
      as a prognostic marker in cancer patients. These findings suggest that hypoxia
      and/or HIF-1 orchestrates EMT and metastasis through the coordinated regulation
      of different EMT regulators. Our results provide the important link between
      hypoxia and developmental processes regulated by TWIST. The implications of the
      roles of hypoxia and TWIST in early embryonic development are discussed.

PMID- 18635961
TI  - Polypyrimidine tract binding protein regulates IRES-mediated translation of p53
      isoforms.
AB  - The p53 tumor suppressor protein plays a key role in maintaining genomic
      integrity. Enhanced expression of p53 during genotoxic stress is due to both
      increased protein stability and translational upregulation. Previous reports have
      shown that p53 mRNA is translated from an alternative initiation codon to produce
      N-terminal truncated isoform (DeltaN-p53) besides full-length p53. We have
      demonstrated that two internal ribosome entry sites (IRESs) regulate the
      translation of p53 and DeltaN-p53 in a distinct cell cycle phase-dependent
      manner. Here, we report that polypyrimidine tract-binding protein (PTB) is a p53
      IRES interacting trans-acting factor. PTB protein binds specifically to both the
      p53 IRESs but with differential affinity. siRNA-mediated knockdown of PTB protein
      results in reduction of activity of both IRESs and also the levels of both the
      isoforms. It is well known that DNA-damaging agents such as doxorubicin enhance
      the expression of p53. Our results indicate that during doxorubicin treatment,
      PTB protein translocates from nucleus to the cytoplasm, probably to facilitate
      IRES mediated p53 translation. These observations suggest that the relative
      cytoplasmic abundance of PTB protein, under DNA-damaging conditions, might
      contribute to regulating the coordinated expression of the p53 isoforms, owing to
      the differential affinity of PTB binding to the two p53 IRESs.

PMID- 18635962
TI  - Telomere maintenance in Drosophila: rapid transposon evolution at chromosome
      ends.
AB  - The maintenance of terminal sequences is an important role of the telomere, since
      it prevents the loss of internal regions that encode essential genes. In most
      eukaryotes, this is accomplished by the telomerase. However, telomere length can
      also be maintained by other mechanisms, such as homologous recombination and
      transposition of telomeric retrotransposons to the chromosome ends. A remarkable
      situation is the case of Drosophila, where telomerase was lost, and thus
      telomeres managed to be maintained by occasional retrotransposition of telomeric
      elements to the receding ends. In the recent analysis of 12 Drosophila genomes,
      the multiplicity of autonomous and non-autonomous telomere-specific
      retrotransposons has revealed extensive and rapid evolution of telomeric DNA. The
      phylogenetic relationship among these telomeric retrotransposons is congruent
      with the species phylogeny, suggesting that they have been vertically transmitted
      from a common ancestor. In this review, we also suggest that the formation of a
      non-canonical DNA structure at Drosophila telomeres could be the way to protect
      the ends.

PMID- 18635963
TI  - Cyclin A-CDK activity during G1 phase impairs MCM chromatin loading and inhibits
      DNA synthesis in mammalian cells.
AB  - Progression through the mammalian cell division cycle is regulated by the
      sequential activation of cyclin-dependent kinases, CDKs, at specific phases of
      the cell cycle. Cyclin A-CDK2 and cyclin A-CDK1 phosphorylate nuclear substrates
      during S and G(2) phases, respectfully. However, the DNA helicase complex, MCM2
      7, is loaded onto the origin of replications in G(1), prior to the normally
      scheduled induction of cyclin A. It has previously been shown that cyclin A-CDKs
      phosphorylate MCM2 and MCM4 in vitro, thereby diminishing helicase activity.
      Thus, in this study we hypothesize that, in vivo, cyclin A-CDK activity during
      G(1) would result in an inhibition of progression into the S phase. To test this,
      we establish an in vivo method of inducing cyclin A-CDK activity in G(1) phase
      and observe that activation of cyclin A-CDK, but not cyclin E-CDK complexes,
      inhibit DNA synthesis without affecting other G(1) events such as cyclin D
      synthesis, E2F activation and cdc6 loading onto chromatin. We further report that
      the mechanism of this S phase inhibition occurs, at least in part, through
      impaired loading of MCM onto chromatin, presumably due to decreased levels of
      cdt1 and premature phosphorylation of MCM by cyclin A-CDK. In addition to
      providing in vivo confirmation of in vitro predictions regarding cyclin A-CDK
      phosphorylation of the MCM complex, our results provide insight into the cellular
      effects of unscheduled cyclin A-CDK activity in mammalian cells.

PMID- 18635964
TI  - Nurse cell of Trichinella spp. as a model of long-term cell cycle arrest.
AB  - Nurse cell (NC), formed from skeletal muscle cells upon infection with parasitic
      nematode trichina, presents a rare system of long-term suspension in the cell
      cycle. Signaling pathways and general biological functions of Trichinella
      spiralis NC, inferred from network analysis of competitive expression microarray
      data (NC vs. C2C12 myoblasts and myotubes), performed in Ingenuity Pathways
      Analysis (IPA) software and confirmed by Real-Time PCR, are presented. Assuming
      4N DNA content in NC nuclei, its cell cycle arrest is identified herein as a
      hypermitogenic of G(1)-like type, accompanied by induction of senescence,
      underpinned by increased expression of p15, p16 and p57 cell cycle inhibitors, as
      well as overexpression of senescence-associated, beta-galactosidase and numerous
      secretory factors. Growth factor signaling, with predominant role of EGF,
      cytokine signaling and G-protein-coupled receptor signaling, are suggested as
      dominant NC signal transduction pathways. Fos, FosB, STAT6, CREBL2, ID4 and
      retinoic acid dependent nuclear receptors appear to be the main factors
      determining NC specific gene transcription. Antigen presentation, complement
      signaling and beta-amyloid processing pathways are also identified as operating
      in NC. In general, NC pathology is found to pertain to cancer, as well as other,
      including immunological and neurological, disorders.

PMID- 18635965
TI  - Moderate variations in CDC25B protein levels modulate the response to DNA
      damaging agents.
AB  - CDC25B, one of the three members of the CDC25 dual-specificity phosphatase
      family, plays a critical role in the control of the cell cycle and in the
      checkpoint response to DNA damage. CDC25B is responsible for the initial
      dephosphorylation and activation of the cyclin-dependent kinases, thus initiating
      the train of events leading to entry into mitosis. The critical role played by
      CDC25B is illustrated by the fact that it is specifically required for checkpoint
      recovery and that unscheduled accumulation of CDC25B is responsible for
      illegitimate entry into mitosis. Here, we report that in p53(-/-) colon carcinoma
      cells, a moderate increase in the CDC25B level is sufficient to impair the DNA
      damage checkpoint, to increase spontaneous mutagenesis, and to sensitize cells to
      ionising radiation and genotoxic agents. Using a tumour cell spheroid assay as an
      alternative to animal studies, we demonstrate that the level of CDC25B expression
      modulates growth inhibition and apoptotic death. Since CDC25B overexpression has
      been observed in a significant number of human cancers, including colon
      carcinoma, and is often associated with high grade tumours and poor prognosis,
      our work suggests that the expression level of CDC25B might be a potential key
      parameter of the cellular response to cancer therapy.

PMID- 18635966
TI  - Transposon-based mutagenesis identifies short RIP1 as an activator of NFkappaB.
AB  - We used a vector based on the Sleeping Beauty transposon to search for
      constitutive activators of NFkappaB in cultured cells. Dominant mutations were
      produced by random insertion of a tetracycline-regulated promoter, which provided
      robust and exceptionally well-regulated expression of downstream genes. The
      ability to regulate the mutant phenotype was used to attribute the latter to the
      insertional event. In one such mutant, the promoter was inserted in the middle of
      the gene encoding receptor-interacting protein kinase 1 (RIP1). The protein
      encoded by the hybrid transcript lacks the putative kinase domain of RIP1, but
      potently stimulates NFkappaB, AP-1 and Ets-1 activity. Similarly to TNFalpha
      treatment, expression of the short RIP1 was toxic to cells that failed to
      upregulate NFkappaB. The effects of short RIP1 did not require endogenous RIP1 or
      cytokine treatment and coincided with reduced responsiveness to TNFalpha.
      Additional evidence indicates that a similar short RIP1 could be produced
      naturally from the ripk1 locus. Interestingly, elevated expression of short RIP1
      resulted in the loss of full length RIP1 from cells, pointing to a novel
      mechanism through which the abundance of RIP1 and the status of the related
      signaling cascades may be regulated.

PMID- 18635967
TI  - Differential regulation of centrosome integrity by DNA damage response proteins.
AB  - MDC1 and BRIT1 have been shown to function as key regulators in response to DNA
      damage. However, their roles in centrosomal regulation haven't been elucidated.
      In this study, we demonstrated the novel functions of these two molecules in
      regulating centrosome duplication and mitosis. We found that MDC1 and BRIT1 were
      integral components of the centrosome that colocalize with gamma-tubulin.
      Depletion of either protein led to centrosome amplification. However, the
      mechanisms that allow them to maintain centrosome integrity are different. MDC1
      depleted cells exhibited centrosome overduplication, leading to multipolar
      mitosis, chromosome missegregation, and aneuploidy, whereas BRIT1 depletion led
      to misaligned spindles and/or lagging chromosomes with defective spindle
      checkpoint activation that resulted in defective cytokinesis and polyploidy. We
      further illustrated that both MDC1 and BRIT1 were negative regulators of Aurora A
      and Plk1, two centrosomal kinases involved in centrosome maturation and spindle
      assembly. Moreover, the levels of MDC1 and BRIT1 inversely correlated with
      centrosome amplification, defective mitosis and cancer metastasis in human breast
      cancer. Together, MDC1 and BRIT1 may function as tumor-suppressor genes, at least
      in part by orchestrating proper centrosome duplication and mitotic spindle
      assembly.

PMID- 18635968
TI  - Modulation of integrin-linked kinase nucleo-cytoplasmic shuttling by ILKAP and
      CRM1.
AB  - Integrin-linked kinase (ILK) plays key roles in a variety of cell functions,
      including cell proliferation, adhesion and migration. Within the cell, ILK
      localizes to multiple sites, including the cytoplasm, focal adhesion complexes
      that mediate cell adhesion to extracellular substrates, as well as cell-cell
      junctions in epidermal keratinocytes. Central to understanding ILK function is
      the elucidation of the mechanisms that regulate its subcellular localization. We
      now demonstrate that ILK is imported into the nucleus through sequences in its N
      terminus, via active transport mechanisms that involve nuclear pore complexes. In
      addition, nuclear ILK can be rapidly exported into the cytoplasm through a CRM1
      dependent pathway, and its export is enhanced by the type 2C protein phosphatase
      ILKAP. Nuclear localization of ILK in epidermal keratinocytes is associated with
      increased DNA synthesis, which is sensitive to inhibition by ILKAP. Our studies
      demonstrate the importance for keratinocyte proliferation of ILK regulation
      through changes in its subcellular localization, and establish ILKAP and CRM1 as
      pivotal modulators of ILK subcellular distribution and activity in these cells.

PMID- 18635969
TI  - Signaling by dopamine regulates D2 receptors trafficking at the membrane.
AB  - sGi2 is a spliced variant of the GTP-binding protein G(alpha i2). By difference
      with G(alpha i2), which is mainly present at the plasma membrane, sGi2 is
      localized in intracellular compartments. The splicing event generates a novel C
      terminal region in sGi2, which is necessary for its intracellular localization.
      The role of sGi2 is presently unknown, although its intracellular localization
      might underlie a possible role in the regulation of trafficking of 7TM receptors.
      Here, we show that sGi2 complexes with dopamine D2 receptors (D2R) in striatal
      neurons. The sGi2-D2R complex is readily observed in immunoprecipitation studies
      using specific antibodies for both proteins on mouse striatal extracts, which
      identify D2-specific bands of >80 KDa suggesting sGi2 interactions with D2R
      dimers. Importantly, the sGi2-D2R complex in the absence of receptor stimulation
      is mostly found in intracellular perinuclear areas in primary neuronal cultures.
      Treatment of neurons with quinpirole, a D2-specific agonist, results into
      diffusion of D2R and sGi2 staining throughout the cell and into neurites and
      membranes. This suggests that dopamine could regulate availability of D2
      receptors at the cell surface. The formation of sGi2-D2R complex is mediated
      through the interaction of sGi2 with the third intracellular loop of D2Rs. As
      functional consequence of the D2R-sGi2 interaction, we observed a reduction of D2
      binding sites at the plasma membrane, when the two proteins are co-expressed in
      transfected cells. Altogether these studies identify sGi2 as a D2R interacting
      protein involved in the regulation of D2R at the membrane through a dopamine
      mediated mechanism.

PMID- 18635970
TI  - Distinct proliferative and transcriptional effects of the D-type cyclins in vivo.
AB  - The D-type cyclins (D1, D2 and D3) are components of the cell cycle machinery and
      govern progression through G(1) phase in response to extracellular signals.
      Although these proteins are highly homologous and conserved in evolution, they
      contain distinct structural motifs and are differentially regulated in various
      cell types. Cyclin D1 appears to play a role in many different types of cancer,
      whereas cyclins D2 and D3 are less frequently associated with malignancy. In this
      study, we transiently expressed cyclin D1, D2 or D3 in hepatocytes and analyzed
      transcriptional networks regulated by each. All three D-type cyclins promoted
      robust hepatocyte proliferation and marked liver growth, although cyclin D3
      stimulated less DNA synthesis than D1 or D2. Accordingly, the three D-type
      cyclins similarly activated genes associated with cell division. Cyclin D1
      regulated transcriptional pathways involved in the metabolism of carbohydrates,
      lipids, amino acids, and other substrates, whereas cyclin D2 did not regulate
      these pathways despite having an equivalent effect on proliferation. Comparison
      of transcriptional profiles following 70% partial hepatectomy and cyclin D1
      transduction revealed a highly significant overlap, suggesting that cyclin D1 may
      regulate diverse cellular processes in the regenerating liver. In summary, these
      studies provide the first comparative analysis of the transcriptional networks
      regulated by the D-type cyclins and provide insight into novel functions of these
      key cell cycle proteins. Further study of the unique targets of cyclin D1 should
      provide further insight into its prominent role in proliferation, growth and
      cancer.

PMID- 18635971
TI  - Caveolin-1 interacts with a lipid raft-associated population of fatty acid
      synthase.
AB  - Fatty Acid Synthase (FASN), a cytoplasmic biosynthetic enzyme, is the major
      source of long-chain fatty acids, particularly palmitate. Caveolin-1 (Cav-1) is a
      palmitoylated lipid raft protein that plays a key role in signal transduction and
      cholesterol transport. Both proteins have been implicated in prostate cancer
      (PCa) progression, and Cav-1 regulates FASN expression in a mouse model of
      aggressive PCa. We demonstrate that FASN and Cav-1 are coordinately upregulated
      in human prostate tumors in a hormone-insensitive manner. Levels of FASN and Cav
      1 protein expression discriminated between localized and metastatic cancers, and
      the two proteins exhibited analogous subcellular locations in a tumor subset.
      Endogenous FASN and Cav-1 were reciprocally co-immunoprecipitated from human and
      murine PCa cells, indicating that FASN forms a complex with Cav-1. FASN, a
      cytoplasmic enzyme, was induced to associate transiently with lipid raft
      membranes following alterations in signal transduction within the Src, Akt and
      EGFR pathways, suggesting that co-localization of FASN and Cav-1 is dependent on
      activation of upstream signaling mediators. A Cav-1 palmitoylation mutant, Cav
      1(C133/143/156S), that prevents phosphorylation by Src, did not interact with
      FASN. When overexpressed in Cav-1-negative PCa cells, Cav-1(C133/143/156S) caused
      a reduction of both Src and Akt levels, as well as of their active,
      phosphorylated forms, in comparison with wild type Cav-1. These findings suggest
      that FASN and Cav-1 physically and functionally interact in PCa cells. They also
      imply that palmitoylation within this complex is involved in tumor growth and
      survival.

PMID- 18635972
TI  - Assessment of the validation of blood pressure monitors: a statistical
      reappraisal.
AB  - Protocols to determine the accuracy of noninvasive blood pressure monitors have
      been published by the Association for the Advancement of Medical Instrumentation,
      the British Hypertension Society, and the European Society of Hypertension (ESH).
      We compared the statistical basis for each of these protocols. Although the
      Association for the Advancement of Medical Instrumentation and British
      Hypertension Society protocols require a minimum of 85 participants, the ESH
      protocol requires only 33 participants. The reduced sample size results in a
      reduction in statistical power from 98 to 70%, which brings into question the
      applicability of the ESH (International) protocol.

PMID- 18635973
TI  - Risk of atrial fibrillation in dipper and nondipper sustained hypertensive
      patients.
AB  - OBJECTIVE: The risk of atrial fibrillation (AF) in sustained hypertensive
      patients with different circadian blood pressure (BP) patterns is unknown. We
      investigated the risk of new onset AF in dipper and nondipper sustained
      hypertensive patients. METHODS: The occurrence of AF was evaluated in 1141
      patients aged > or = 40 years with sustained hypertension (clinic BP > or = 140
      and/or 90 mmHg and daytime BP > or = 135 and/or 85 mmHg). Among these patients,
      783 had night-time systolic BP fall > or = 10% (dippers) and 358 had night-time
      BP decline <10% (nondippers). RESULTS: During the follow-up (6.1+/-3.2, range 0.5
      12.9 years), AF occurred in 43 patients. The AF rate per 100 patient-years in
      dippers and nondippers was 0.38 and 1.13, respectively. AF free survival was
      significantly different between the groups (P=0.0002). After adjustment for other
      covariates, including left atrial enlargement or left ventricular hypertrophy
      (these variables were analyzed in separate models because of a strong association
      between them) and 24-h BP, Cox regression analysis showed that the risk of AF was
      significantly higher in nondippers than in dippers [nondippers vs. dippers,
      relative risk (RR) 2.02, 95% confidence interval (CI) 1.08-3.79, P=0.028 in the
      model including left atrial enlargement, and RR 1.97, 95% CI: 1.05-3.69, P=0.035
      in the model including left ventricular hypertrophy]. CONCLUSION: This study
      shows that nondipper sustained hypertensive patients have a two-fold greater risk
      of developing AF than dipper ones. This aspect could partly contribute to explain
      the higher cardiovascular risk previously observed in nondipper hypertensive
      patients.

PMID- 18635974
TI  - Comparison of a radial artery compression device with invasive radial artery
      blood pressure monitoring.
AB  - OBJECTIVE: The goal of this study was to validate the accuracy of the Primo
      radial artery compression device (RACD) according to the guidelines recommended
      by the American National Standards Institute/Association for the Advancement of
      Medical Instrumentation (AAMI) SP10-2002 Standards for Electronic or Automated
      Sphygmomanometers. METHODS: A prospective, nonblind, convenience sample trial at
      a level 1 trauma center (annual emergency department census 70,000) enrolled 17
      adult patients with preexisting radial artery line catheters (RAL). Each patient
      had 10 blood pressure measurements giving an n=170. This number is consistent
      with calculations on the basis of the American National Standards Institute/AAMI
      guidelines. RESULTS: The mean arterial pressures (MAPs), systolic blood pressures
      (SBPs), and diastolic blood pressures (DBPs) measured by both the RACD and the
      RAL were compared. The R for the RAL/RACD were 0.94, 0.96, and 0.85 for MAP, SBP,
      and DBP, respectively (P<0.05). The mean difference between the RAL MAP and the
      RACD MAP was +1.0 mmHg (95% confidence interval, -1.69 to -0.33). The mean SBP
      difference was -2.8 mmHg (SD 6.4 mmHg) and the mean DBP difference was +2.6 mmHg
      (SD 5.7 mmHg). CONCLUSION: The RACD meets the guidelines for automated blood
      pressure monitors set by the AAMI SP10-2002 Standards for Electronic or Automated
      Sphygmomanometers with an accuracy of +/- 5 mmHg and SD of 8 mmHg or less for
      both SBP and DBP measurements.

PMID- 18635975
TI  - Blood pressure abnormalities in children with chronic kidney disease.
AB  - OBJECTIVES: Disturbances of blood pressure (BP) rhythms have been demonstrated in
      patients with various degrees of renal impairment. The purpose of this study was
      to determine the prevalence of BP abnormalities in children with chronic kidney
      disease (CKD) and evaluate possible factors associated with nocturnal BP
      abnormalities. METHODS: 42 children between 2 and 19 years of age with CKD stages
      2-5 completed 24-h ambulatory BP monitoring. RESULTS: The percentage of patients
      with daytime hypertension was less than 10% but rates were higher at nighttime
      where 14% had systolic and 24% diastolic hypertension. A similar percentage of
      patients had a BP load >50%. BP abnormalities that were not evident in clinic BP
      readings were identified in 49% of the participants. The nocturnal BP dipping
      percentage tended to decrease as the estimated glomerular filtration rate
      decreased. Proteinuria was significantly associated with nocturnal BP nondipping.
      CONCLUSION: 24-h ambulatory BP monitoring may provide additional insight into
      hypertension in pediatric patients as early as CKD stage 2. Several BP
      abnormalities were identified that were not evident in casual BP measurements
      including nocturnal hypertension, elevated BP load, and nocturnal BP nondipping.

PMID- 18635976
TI  - Changes of blood pressure and heart rate during sexual activity in healthy
      adults.
AB  - OBJECTIVE: This study is to observe the changes of blood pressure (BP), heart
      rate (HR), double product (DP) and heart rate variability during sexual activity
      in healthy adults before we cover patients with chronic cardiovascular disease.
      METHODS: Forty-nine participants grouped by sex, 22 males, aged 40.6+/-7.8 years;
      27 females, aged 40.3+/-7.8 years, underwent simultaneous ambulatory monitoring
      of BP and HR for 24 h. During the monitoring period, sexual activity of the
      participants with man-on-top in their familiar environment was performed.
      Participants were requested to measure BP manually at the beginning of each
      sexual phase and three times after orgasm in every 10-min interval and 60 min
      after orgasm. For each individual, eight measuring values, respectively, about
      BP, HR, DP and heart rate variability were obtained from baseline to 1 h after
      orgasm. The data were statistically analyzed with paired t-test and the
      significant level was set at P<0.05. RESULTS: In both groups, the peak BP did not
      appear at orgasm, but at the beginning of plateau and dropped to baseline level
      at 10 min after orgasm (male 141.41+/-17.13/91.05+/-13.69 vs. 120.14+/
      11.07/72.86+/-7.78 mmHg, female 121.67+/-16.61/77.37+/-15.03 vs. 109.37+/
      10.54/67.19+/-9.41 mmHg). The peak HR occurred at the beginning of orgasm, and
      dropped to baseline level 10-20 min after orgasm (male 96.36+/-11.96 vs. 75.41+/
      9.02 bpm, female 90.19+/-10.38 vs. 71.44+/-5.68 bpm). DP of both groups elevated
      at the beginning of plateau and orgasm then decreased to baseline level 10 min
      after orgasm (male 12964.27+/-2659.17 vs. 9134.09+/-1469.58 mmHg bpm, female
      10044.48+/-1777.89 vs. 7841.30+/-1023.79 mmHg bpm). All the results showed that
      BP, HR and DP have mild to moderate changes during sexual activity in healthy
      adults. CONCLUSION: Using ambulatory technology to monitor BP and HR helps us to
      get the real data in participants during sexual activity. BP, HR and DP increase
      just slightly for a short time and recover to baseline level soon after sexual
      activity in healthy adults. The physical exhaustion during sexual activity is
      within the range of the daily-life workload.

PMID- 18635977
TI  - Using a home blood pressure monitor: do accompanying instructional materials meet
      low literacy guidelines?
AB  - To evaluate the readability and related features of English language Quick
      Reference Guides (QRGs) and User Manuals (UMs) accompanying home blood pressure
      monitors (HBPMs). We evaluated QRGs and UMs for 22 HBPMs [arm (n=12); wrist
      (n=10)]. Using established criteria, we evaluated reading grade level, language
      availability, dimensions, text point size, use of illustrations,
      layout/formatting characteristics, and emphasis of key points of English-language
      patient instructions accompanying HBPMs. Readability was calculated using
      McLaughlin's Simplified Measure of Gobbledygoop. Items from the Suitability of
      Materials Assessment and User-Friendliness Tool were used to assess various
      layout features. Simplified Measure of Gobbledygoop scores of both QRGs (mean+/
      SD=9.1+/-0.8) and UMs (9.3+/-0.8) ranged from 8th to 10th grade. QRGs and UMs
      presented steps in chronological order, used active voice throughout, avoided use
      of specialty fonts, focused on need to know, and used realistic illustrations.
      Seven sets of instructions included all seven key points related to proper HPBM
      use, whereas three sets of instructions included less than or equal to three key
      points (mean=4.8+/-1.9). Although most QRGs and UMs met at least some recommended
      low-literacy formatting guidelines, all instructional materials should be
      developed and tested to meet the needs of the patient population at large. Key
      points related to proper HBPM use should not only be included within these
      instructions, but highlighted to emphasize their importance.

PMID- 18635978
TI  - Omron HEM-711 DLX home Blood pressure monitor passes the European Society of
      Hypertension International Validation Protocol.
AB  - The Omron HEM-711 DLX home Blood pressure monitor was tested using the European
      Society of Hypertension International Protocol in 33 patients. The average error
      was 0.9+/-5.2 (SD) (range: -12 to 10 mmHg)/-0.8+/-5.6 (-19 to 8). It can be
      recommended for use by patients. With all automatic devices it is, however,
      important to validate its accuracy in each individual patient who uses it.

PMID- 18635979
TI  - The HoMedics BPA-200 and BPA-300 home blood pressure devices fail the European
      Society of Hypertension International Protocol and cannot be recommended for
      patient use.
AB  - We have tested two home blood pressure monitors made by the HoMedics, Inc., 300
      Pontiac Trail, Commerce Township, Michigan 48390, USA, using the European Society
      of Hypertension International Protocol. Both failed and we believe it is
      important to get this into the literature quickly to protect patients and
      practitioners.

PMID- 18635980
TI  - Automated device that complies with current guidelines for office blood pressure
      measurement: design and pilot application study of the Microlife WatchBP Office
      device.
AB  - OBJECTIVE: Current guidelines for office blood pressure (BP) measurement
      recommend mercury devices, both arms measurement in the initial assessment and at
      least duplicate measurements at follow-up visits. This study presents the design
      and a pilot application study of an automated device that fulfils American,
      European, and International guidelines for office BP measurement. DESIGN AND
      FUNCTIONS: The Microlife WatchBP Office is a professional electronic mercury-free
      device with three function modes designed for: (a) initial assessment: triplicate
      automated simultaneous oscillometric both arms measurement at 60-s intervals and
      when there is a consistent interarm difference more than 20 mmHg systolic and/or
      more than 10 mmHg diastolic, the arm with the higher BP is indicated. (b) Follow
      up assessment: triplicate automated oscillometric single arm measurements at 60-s
      intervals and their average is displayed. (c) Auscultatory measurement: by an
      observer using a stethoscope and a digital countdown BP display for patients with
      arrhythmias and other individuals in whom the oscillometric measurement is not
      accurate. PILOT APPLICATION STUDY: The 'initial assessment' mode was applied by
      three physicians in 63 patients (189 readings). Average interarm systolic BP
      difference was 0.04+/-5.1 mmHg and diastolic 0.4+/-3.2 mmHg. A value more than 10
      mmHg interarm difference in nine systolic BP readings (5%) and three (2%)
      diastolic. No patient had a consistent interarm difference more than 10 mmHg in
      all three or two of the three readings. CONCLUSION: The Microlife WatchBP Office
      professional device fulfils current international requirements for office BP
      measurement and seems to overcome several limitations of this method when applied
      in clinical practice.

PMID- 18635981
TI  - Problems with the AAMI study of the HoMedics BPA-300 recently published by
      Yarows.

PMID- 18635983
TI  - Context for WOC practice: larval debridement therapy, abdominal fistula pouch,
      hyperglycemia, and wound infections.

PMID- 18635984
TI  - Statistical and clinical significance: are they one and the same?

PMID- 18635985
TI  - Is larval (maggot) debridement effective for removal of necrotic tissue from
      chronic wounds?
AB  - BACKGROUND: Debridement is considered an essential component of wound bed
      preparation. Multiple techniques for removing necrotic tissue from wounds have
      been identified, but evidence concerning the efficacy and indications for each
      technique varies. OBJECTIVES: We sought to identify evidence related to the
      efficacy of maggot (larval) debridement for the removal of necrotic tissue and
      its impact on wound healing. SEARCH STRATEGY: A systematic review of electronic
      databases was undertaken using the following key words: (1) debridement, (2)
      maggot therapy, and (3) larval therapy. All prospective and retrospective studies
      published between January 1960 and February 2008 that compared maggot (larval)
      debridement therapy for pressure ulcers, leg ulcers, or burn wounds to autolytic
      debridement or other debridement techniques were included in the review. RESULTS:
      The evidence base for the efficacy of maggot debridement therapy (MDT) in the
      management of necrotic wounds is sparse. There is insufficient evidence to
      conclude that MDT is as effective as or more effective than other debridement
      methods, or that MDT promotes wound healing. IMPLICATIONS FOR PRACTICE: Even
      though clinical evidence supporting the use of MDT for debridement of wounds is
      lacking, clinical experience strongly suggests that this technique is an
      effective and safe method of debridement for selected patients. Expert clinicians
      with extensive experience using this technique usually advocate MDT as a last
      resort treatment when conservative means for wound bed preparation prove
      unsuccessful or when surgery is not feasible owing to comorbid conditions or
      other considerations.

PMID- 18635986
TI  - The WOC nurse and industry representatives: fostering a relationship.

PMID- 18635987
TI  - Retrospective versus prospective cohort study designs for evaluating treatment of
      pressure ulcers: a comparison of 2 studies.
AB  - The effect of interventions designed to help prevent or treat pressure ulcers can
      be assessed through a number of study designs including retrospective and
      prospective cohort studies. This article highlights the strengths and weaknesses
      of these 2 approaches to data collection and analysis. Retrospective studies
      provide for analysis of large amounts of data with less investment, while
      prospective cohorts may capture clinically relevant variables missing from
      retrospective data sets. Prospective studies may also gather data in a more
      consistent and accurate manner. However, ensuring comparability between the
      various study groups (patient groups managed with different products or
      interventions) remains a challenge for both prospective and retrospective cohort
      studies. In retrospective cohort studies, allocation may be based on arbitrary
      reimbursement decisions, while prospective cohort designs may mask unequal
      distribution of key risk factors.

PMID- 18635989
TI  - Impact of tight glucose control on postoperative infection rates and wound
      healing in cardiac surgery patients.
AB  - Approximately 1 of every 4 hospitalized patients has diabetes mellitus (DM). Type
      2 DM is commonly associated with cardiovascular disease, and many undergo
      cardiothoracic surgical procedures such as coronary artery bypass grafting.
      Persons with type 2 DM are at higher risk for postoperative infections due to a
      muted immune response, the effects of hyperglycemia on neutrophil function and
      pathogen proliferation, and the negative effects of diminished perfusion.
      Hyperglycemia resulting from insulin resistance is common in critically ill
      patients, including those who have not previously been diagnosed with diabetes.
      Factors contributing to postoperative hyperglycemia include increased levels of
      catecholamines, growth hormone, and corticosteroids. Higher glucose levels may
      also result from pharmacologic agents commonly used during and following surgery,
      such as heparin and beta-blockers. Tight glucose control has been shown to
      improve survival and reduce morbidity after cardiac surgery and lower the
      incidence of wound complications. In contrast, the traditional approach to
      glucose management, sliding-scale insulin administration, does not provide
      adequate control. Continuous insulin infusion protocols may significantly reduce
      postoperative morbidity and mortality in patients with type 2 DM and
      hyperglycemia associated with metabolic syndrome.

PMID- 18635991
TI  - Risk assessment for pressure ulcer: a hospital-based study.
AB  - AIM: To identify patients at risk for developing pressure ulcer among
      hospitalized patients and the prevalence of pressure ulcer in this group.
      PATIENTS AND METHOD: A prospective study included 100 patients from medical and
      surgical wards. Data were collected on admission, and subjects were followed up
      at regular intervals. The Waterlow pressure ulcer risk assessment tool was
      completed and patients were stratified "as not at risk," "at risk", "high risk",
      and "very high risk". Subjects were then monitored for 2 weeks and the actual
      incidence of pressure ulcer formation was analyzed in the various risk groups.
      RESULTS: Of 100 patients studied, 20% were at risk, 10% were assessed at high
      risk, and 7% were classified as at very high risk for developing a pressure
      ulcer. Necessary preventive measures were taken (posture change, specialized
      beds/mattresses, nursing care, nutritional input, etc) for those patients at risk
      of development of pressure ulcer. Four of 7 patients (57.1%) who were at very
      high-risk developed pressure ulcer as compared with 2 of 10 patients (20%)
      categorized in the high-risk category within a period of 2 weeks. No patient who
      was classified as not at risk on the Waterlow pressure ulcer risk assessment tool
      developed a pressure ulcer within the observation period. CONCLUSION: Pressure
      ulcers developed in identified risk groups despite adequate available preventive
      measure being taken to prevent their development. It is of extreme importance to
      identify patients at risk for the development of pressure ulcers so that
      preventive measures can be instituted to reduce the incidence of hospital
      acquired pressure ulcers.

PMID- 18635992
TI  - Maggot debridement therapy: serious bleeding can occur: report of a case.
AB  - Maggot debridement therapy is generally a safe therapy that is typically used as
      a last resort treatment for debriding wounds in patients with multiple
      comorbidities. We describe a case of serious bleeding in an 87-year-old woman
      treated in our wound care center for a mixed arterial-venous ulcer of the right
      leg. Daily home visits were completed by a wound care nurse, resulting in prompt
      recognition and management of the bleeding. The patient was transported to
      hospital via an ambulance, and rapidly stabilized with intravenous fluids and a
      blood transfusion. She subsequently returned to the home care setting for
      additional management of her lower extremity wound.

PMID- 18635993
TI  - Management of fistulae in the abdominal region.
AB  - OBJECTIVE: We evaluated a new fistula and wound management system; ostomy and
      wound care nurses were queried about willingness to use the product in future
      patients, product wear time and pouch leakage, perifistular skin condition,
      access for wound care, pouching time, patient mobility and comfort, odor
      management, pouch flexibility, adhesiveness, and erosion. A health economic
      assessment was also done. METHOD: Twenty-two patients (5 males and 17 females)
      with an abdominal fistula participated in the study. Participants tested 75
      pouches, representing an average of 3.4 pouches per subject. The investigator at
      each site who performed the pouch changes completed a questionnaire at baseline,
      during the test, and after testing the pouches. Participants also completed a set
      of questions after each test pouch was removed. RESULTS: In 21 of 22 cases, the
      nurses would consider using the new system on future patients. After each pouch
      removal, patients were asked whether they were able to move around while wearing
      the test pouch and they answered yes 95% of the time. The new system was found to
      have significantly longer wear time than traditional systems (P = .003), but the
      average time spent on changing the pouches was not significantly different (P =
      .07). Access for fistula and wound care was rated as excellent in the new
      pouching system, and comfort was rated as very good. CONCLUSION: The results of
      the study suggest that all of the key requests received from nurses for an
      improved system for fistula and wound management were met by the new system.

PMID- 18635994
TI  - Stoma surgery for colorectal cancer: a population-based study of patient
      concerns.
AB  - OBJECTIVE: The difficulties and concerns of colorectal cancer patients with an
      ostomy are not well documented. This study describes the difficulties experienced
      by colorectal cancer patients with a temporary or permanent ostomy over the 2
      year period following their diagnosis. Patients' satisfaction with the
      information provided to them by their healthcare providers was also assessed.
      METHODS: Colorectal cancer patients with an ostomy (N 5332) recruited through a
      cancer registry completed telephone interviews at approximately 5, 12, and 24
      months following diagnosis. RESULTS: Painful or irritated peristomal skin and
      odor and noise from the appliance were the most commonly reported stoma-related
      difficulties. The proportion of participants reporting these difficulties
      decreased over time. Provision of preoperative information was comprehensive, and
      satisfaction with preoperative information was high. However, 34% of patients
      said they were not seen by an ostomy nurse prior to surgery. CONCLUSIONS: The
      ostomy nurse may be ideally placed to initiate, develop, and implement
      survivorship care plans for colorectal cancer patients.

PMID- 18635995
TI  - Continence care.

PMID- 18635996
TI  - Pathways to WOC nurse certification.

PMID- 18635997
TI  - Maggot debridement therapy: a case study.
AB  - A 59-year-old woman arrived at Vancouver General Hospital after a motor vehicle
      accident in which she sustained massive degloving injuries to both lower
      extremities. Due to her faith (she is a Jehovah's Witness), traditional
      interventions such as surgical debridement and revision were not possible and
      consent to receive blood products was not provided. WOC nursing was consulted at
      the request of the family to utilize maggot debridement therapy (MDT) to treat
      her necrotic lower extremities. Initially, the use of the Lucilia sericata larvae
      (maggots) was viewed as a last effort to save the patient from septicemia while
      awaiting surgery. However, after MDT was applied once a week for a period of 6
      weeks, both legs were rendered free of necrotic tissue. The patient is now free
      of infection and awaiting surgery for placement of skin grafts over healthy
      granulation tissue achieved after MDT.

PMID- 18635999
TI  - Reduced systemic oxygen extraction does not prove muscle dysfunction in PAH.

PMID- 18636001
TI  - Intuition: believe it or not ... but place it in your toolbox.

PMID- 18636002
TI  - Best practices in telephonic case management.

PMID- 18636003
TI  - What can claims data tell the case manager?
AB  - PURPOSE OF STUDY: This article seeks to use claims data to evaluate provision of
      service in 4 diagnosis-related groups (DRGs) for a rural hospital in an effort to
      better understand an increasing length of stay (LOS) and a decreasing case mix
      index (CMI). The complexity of the patient drives the services delivered, but
      does it drive the DRG assignment? Reimbursement for inpatient medical services is
      driven by DRG assignment and has an associated expected LOS. LOS is a result of
      the combination of physician practice patterns, available services, and the
      medical complexity of the patient. Itemized hospital charges can provide
      sufficient information to examine service delivery in broad categories. When
      compared to the services delivered through a professional protocol, physician
      practice benchmarks can be created. Identifying those services that are
      consistent and inconsistent with the protocol can prove illuminating and point to
      under- and overutilization, inadequate documentation, as well as opportunities
      for physician education. PRIMARY PRACTICE SETTING(S): Although this study was
      undertaken using hospital inpatient claims, the study can be recreated in almost
      any practice setting where there is a consistent mechanism to capture the
      provision of services. In the broader scheme, as case management practice
      transitions from functional models to outcome models, the relevance of these
      issues becomes more profound. The information gleaned from such a study can not
      only benefit case management administrators but inform and impact those involved
      in case management at any level. Indeed, the information can illuminate practice
      patterns for those beyond the case management sector and can include financial
      administrators, physician practice managers, and physicians. METHODOLOGY AND
      SAMPLE: A combination of developmental and casual-comparative methodology was
      applied to this study. The results of this study will create baselines for
      current practice patterns from which improvement opportunities in both resource
      and quality management can be identified. Casual-comparative research identifies
      a consequence and attempts to trace it back to its origin. In this case, the
      discharge diagnosis, a function of documentation, is the consequence, and this
      study attempts to determine whether physician practice patterns are accurately
      reflected in that documentation. The sample consisted of the itemized claims data
      for all patients discharged from Putnam Community Medical Center (PCMC) between
      January 1 and June 30, 2006, with a discharge DRG of 127, 089, 088, or 143.
      Records that did not have sufficient charges to map provision of care were
      excluded. CONCLUSIONS: An analysis of the charges for the selected DRGs
      illustrates the actual care provided to the patient, rather than the resultant
      coding based on physician documentation. This finding leads to 1 of 3
      conclusions: physician documentation is inadequate to allow accurate coding of
      services delivered; the physician may be ordering unnecessary
      services/interventions; or medical record coding may be suboptimal. The scope of
      today's acute care case management department often includes social work,
      utilization review, discharge planning, and resource management. Within that
      scope is the accountability for certain aspects of the hospital's financial
      performance, not the least of which is LOS. A clear understanding of the payer
      mix and the effect upon financial performance is necessary. Management of DRG
      reimbursement-based contracts requires investigation of practice patterns that
      may increase LOS, and documentation that can affect medical coding decisions. The
      results of these activities can guide clinical practice guideline adoption or
      development and identify opportunities to fine-tune documentation to better
      reflect services provided and support utilization decisions. IMPLICATIONS FOR
      CASE MANAGEMENT PRACTICE: Case Management Society of America (CMSA) Standards of
      Practice charge the profession with engaging strategies whenever possible to
      improve outcomes. Performance indicators include advocacy, resource
      management/stewardship, and research utilization. Addressing physician practice
      patterns and reducing nonessential services are examples of advocacy at the
      service-delivery level. These activities are also examples of resource
      management/stewardship as they seek to "promote the most effective and efficient
      use of healthcare services and financial resources" (CMSA, 2002, p. 19). The
      standards of practice call for research utilization and encourage research
      activities that are appropriate to case management practice and the subsequent
      sharing of those findings. In this way, the profession is enriched and promotes
      cost-effective, quality care and case management practice.

PMID- 18636005
TI  - Case management implications of celiac disease.
AB  - PURPOSE OF STUDY: The purpose of this article is to educate case managers on an
      autoimmune disorder, celiac disease, that is seen with increased frequency due to
      recent improvements in diagnostic testing. After reading this article, case
      managers will PRIMARY PRACTICE SETTING(S): Outpatient case management, although
      patients with celiac disease may be encountered in any setting.
      FINDINGS/CONCLUSIONS: Celiac disease is a genetic autoimmune disease affecting up
      to 1% of the population. The majority of people with celiac disease do not know
      they have it. With new diagnostic tests available on the marketplace, increasing
      numbers of people are being diagnosed with celiac disease. Case managers are
      likely to encounter patients with celiac disease as either a primary or secondary
      diagnosis. Celiac disease may cause gastrointestinal symptoms such as gas,
      diarrhea, or bloating, and is also associated with osteoporosis, other autoimmune
      disorders, and certain types of cancer. For children, it is a common disorder
      underlying growth delays. Celiac disease is present in 3%-8% of persons with
      diabetes and may affect glycemic control in these patients. The only known
      treatment of celiac disease is a lifelong gluten-free diet. The increased number
      of individuals diagnosed with celiac disease has led to an increase in products
      available, as well as in research on treatment alternatives. IMPLICATIONS FOR
      CASE MANAGEMENT PRACTICE: People with celiac disease report challenges in
      adhering to the gluten-free diet. Case managers can assist patients in accessing
      appropriate therapy, including nutrition counseling and monitoring services. They
      may also advocate for testing of patients in high-risk groups such as persons
      with diabetes, and those with unexplained gastrointestinal symptoms. In working
      with celiac patients, case managers should address psychosocial issues as well as
      knowledge deficits. Patients may need particular support integrating the gluten
      free diet with other requirements, including heart healthy or diabetic diets.
      Case managers can help patients identify reliable sources of information and
      products. Case managers still have a role to play in educating patients and
      supporting adherence with this lifelong dietary regimen.

PMID- 18636007
TI  - The providers' coordination of care: a model for collaboration across the
      continuum of care.
AB  - OBJECTIVE: With guidance from Health Services Advisory Group, the Arizona
      Medicare Quality Improvement Organization, a Prescott, Arizona, workgroup
      consisting of a hospital, nursing home, and 2 home health agencies have come
      together to improve continuity of care as related to pressure ulcer prevention
      and treatment. METHODS: Weekly, then monthly, meetings were held to develop
      recommendations for practice standardization, a treatment grid for easy
      reference, an educational module with posttests, and standardized physicians'
      orders, which were developed and disseminated to the local provider community.
      RESULTS: More than 200 staff members were educated at Yavapai Regional Medical
      Center (YRMC), local skilled nursing facilities, and home health agencies. In
      addition, new employees and nursing students are now educated on the Providers'
      Coordination of Care Educational Module at YRMC. The Module has been placed on
      the hospital's Web site and offered free to all interested parties. IMPLICATIONS
      FOR CASE MANAGEMENT: With pressure being mounted by Centers for Medicare &
      Medicaid Services, the Office of the Inspector General (OIG), and the general
      public, the role of the case manager (in all practice settings) will increasingly
      become more crucial. Through development of a network of local venues of care,
      the case manager can facilitate care transitions throughout the healthcare system
      with the goal of improved outcomes for the patient regardless of setting.
      Providing the right care, in the right setting to improve patient care, can only
      benefit our aging and declining populations. CONCLUSIONS: Cross-setting work will
      become more essential as the Centers for Medicare & Medicaid Services goal of pay
      for-performance is realized across all care settings. As a national priority,
      pressure ulcer prevention and treatment needs to be embraced by all settings. It
      serves the patient, as well as the healthcare providers, to improve care
      regardless of setting or competition. Positive results can be accomplished if the
      best interests of the patient are kept at the forefront. To this end, obstacles
      of competition and individual facility possessiveness must be overcome to achieve
      the desired results. Having the right mix of professionals will enhance the
      results. The lessons learned here can be used in any across-the-settings
      initiative.

PMID- 18636008
TI  - The birth of InterQual: evidence-based decision support criteria that helped
      change healthcare.
AB  - PURPOSE/OBJECTIVES: InterQual evidence-based clinical decision support criteria
      are used by thousands of organizations in healthcare. What industry trends led to
      their creation, and what accounts for their longevity and widespread acceptance?
      PRIMARY PRACTICE SETTINGS(S): Hospitals, health systems, and managed care
      organizations. FINDINGS/CONCLUSIONS: Although the healthcare puzzle sometimes
      seems too complicated for anyone to solve, passionate people with good ideas have
      been able to effect substantive and relatively rapid change throughout healthcare
      history.

PMID- 18636011
TI  - Postacute levels of care for stroke survivors: a tool for referral.

PMID- 18636012
TI  - Workers' compensation & return to work: it is all about communication...

PMID- 18636013
TI  - Overcoming barriers for a successful return to work.

PMID- 18636014
TI  - The histopathology of BRAF-V600E-mutated lung adenocarcinoma.
AB  - BRAF mutations in lung adenocarcinoma are much less common than the more
      frequently reported and mutually exclusive mutations of KRAS and EGFR genes, and
      the clinical and histologic phenotype of BRAF adenocarcinomas has not been
      described. We analyzed 222 adenocarcinomas of lung lacking KRAS and EGFR
      mutations and identified 10 adenocarcinomas with BRAF-V600E mutation. All BRAF
      V600E mutations were heterozygous. There was a slight female predilection (6:4)
      in these elderly patients (average age 67 y) who were found to have a greater
      than expected incidence of intralobar satellite nodules and N2 node involvement.
      The adenocarcinomas were largely of mixed type with a high incidence of papillary
      (80%) and lepidic growth (50%). Adenocarcinomas with this clinicopathologic
      phenotype may be worthwhile investigating for BRAF-V600E mutation as more
      genetically oriented drug therapies emerge.

PMID- 18636015
TI  - Complications of endovascular polymers associated with vascular introducer
      sheaths and metallic coils in 3 patients, with literature review.
AB  - BACKGROUND: Hydrophilic coatings on arterial introducer sheaths reduce the
      frequency of spasm during cardiac catheterization. Moreover, during treatment of
      cerebral artery aneurysms, hydrophilic coatings on microcatheters ease their
      maneuverability, and polymers within embolization coils enhance neointimal
      fibrosis at the aneurysm neck. Foreign-body giant cell reactions can result when
      a polymer is stripped from its source. CASES 1 AND 2: A 51-year-old man and a 66
      year-old woman underwent coronary angiography via the radial artery, using
      hydrophilic-coated sheaths. They both developed tender lesions at the access site
      2 weeks later. Microscopy of resected lesions showed pieces of hydrophilic
      coating and granulomatous inflammation, as has been reported by others. CASE 3: A
      58-year-old woman underwent embolization of a ruptured distal right internal
      carotid artery aneurysm using polymer-containing coils. Nine months later, she
      began developing multiple right-sided cerebral ring-enhancing lesions. Biopsy
      revealed granulomas and microabscesses, in which polymer filaments were later
      identified. To our knowledge, this complication has not been described
      previously. CONCLUSIONS: Hydrophilic coating may dislodge and induce a prominent
      foreign-body granulomatous response or microabscesses. Although the culprit
      radial artery sheath is now rarely used, embolization coils containing polymers
      are commonly deployed in clinical practice and may be a source of recurrent
      inflammatory lesions.

PMID- 18636016
TI  - Lymphomas involving the breast: a study of 106 cases comparing localized and
      disseminated neoplasms.
AB  - Lymphomas involving the breast account for approximately 2% of extranodal and <1%
      of all non-Hodgkin lymphomas. Our aim in this study was to classify breast
      lymphomas using the World Health Organization classification and then compare
      this classification with clinical, histologic, and radiologic findings as well as
      survival. The study group included 106 patients with breast lymphoma (105 women
      and 1 man). The neoplasms were divided into 2 groups based on extent of disease
      at initial diagnosis: localized disease (n=50) and disseminated disease (n=56).
      The follow-up period ranged from 4 to 252 months (median, 49 mo). Almost all
      (97%) patients presented with a palpable breast mass or masses. In the localized
      group, diffuse large B-cell lymphoma (DLBCL) was most frequent (n=32, 64%). In
      the disseminated group, follicular lymphoma was most frequent and exclusive to
      this group (P=0.0004). Mucosa-associated lymphoid tissue lymphomas occurred in
      both groups without a significant difference in frequency. A variety of other
      types of B-cell and T-cell non-Hodgkin lymphomas and classical Hodgkin lymphoma
      involved the breast at much lower frequency; most of these neoplasms involved the
      breast as part of disseminated disease. The clinical presentation correlated with
      radiologic findings: localized lymphomas presented as solitary masses, whereas
      disseminated lymphomas commonly presented as multifocal masses. There was a
      significant difference in the disease-free survival between patients with
      localized and disseminated DLBCL (P=0.003). In the disseminated group, patients
      with DLBCL had a worse disease-free survival compared with patients with mucosa
      associated lymphoid tissue lymphoma or follicular lymphoma (P=0.01).

PMID- 18636017
TI  - Sox10: a pan-schwannian and melanocytic marker.
AB  - S100 protein is a sensitive marker for melanomas and peripheral nerve sheath
      tumors. It is, however, expressed by other mesenchymal and epithelial tumors.
      Despite its low specificity, S100 protein is valuable for the diagnosis of
      desmoplastic melanomas and peripheral nerve sheath tumors, for which no specific
      marker is available. Sox10 is a neural crest transcription factor crucial for
      specification, maturation, and maintenance of Schwann cells and melanocytes. Anti
      Sox10 antibody was applied to a variety of neural crest-derived tumors,
      mesenchymal and epithelial neoplasms, and normal tissues. Sox10 nuclear
      expression was found in 76 of 78 melanomas (97%) and 38 of 77 malignant
      peripheral nerve sheath tumors (49%) whereas S100 protein was expressed in 71
      melanomas (91%) and 23 malignant peripheral nerve sheath tumors (30%). Sox10 was
      diffusely expressed in schwannomas and neurofibromas. Sox10 reaction was seen
      only in sustentacular cells of pheochromocytomas/paragangliomas, and occasionally
      carcinoid tumors from various organs, but it was not seen in the tumor cells. In
      normal tissues, Sox10 was expressed in Schwann cells, melanocytes, and
      myoepithelial cells of salivary, bronchial, and mammary glands. Sox10 reaction
      was not identified in any other mesenchymal and epithelial tumors except for
      myoepitheliomas and diffuse astrocytomas. Sox10 was expressed by metastatic
      melanomas and nodal capsular nevus in sentinel lymph nodes, but not by other
      lymph node components such as dendritic cells. Our results indicate that Sox10
      will serve as a more sensitive and specific marker for the diagnosis of
      melanocytic and schwannian tumors than S100 protein.

PMID- 18636018
TI  - Luteinized thecomas (thecomatosis) of the type typically associated with
      sclerosing peritonitis: a clinical, histopathologic, and immunohistochemical
      analysis of 27 cases.
AB  - The nature of the distinctive ovarian lesion often associated with sclerosing
      peritonitis, initially considered a variant of luteinized thecoma in the paper
      describing this phenomenon, remains uncertain, as does its long-term prognosis.
      We describe the features of 27 cases, including immunohistochemical analysis of
      13 cases. Sclerosing peritonitis was documented in 25 cases. Patients ranged in
      age from 10 months to 85 years, and typically presented with abdominal distension
      and pain with ascites and sometimes bowel obstruction. The ovarian lesions,
      clinically bilateral in 24 cases, ranged from 2 to 31 cm and often had a striking
      cerebriform aspect. Microscopically, mitotically active spindle cells with weakly
      luteinized cells, variable edema, and entrapped follicles were typical. The
      spindle cells were focally positive with calretinin in 2 cases, CD56 in 2, AE1/3
      in 4, smooth muscle actin in 12, and desmin in 8 cases, and negative with alpha
      inhibin, epithelial membrane antigen, beta-catenin, CD34, and transforming growth
      factor-beta, with focal nuclear positivity for estrogen receptor in 5 and
      progesterone receptor in 11 cases. Luteinized cells were positive with alpha
      inhibin, calretinin, and/or CD56. The peritoneal lesions were strongly positive
      with AE1/3 and exhibited focal weak or moderate positivity with estrogen receptor
      or progesterone receptor in 4 of 8 cases each. Follow-up in 20 cases (mean: 5.9
      y) disclosed no evidence of spread of the ovarian lesion, but 3 patients died of
      sclerosing peritonitis. The findings fail to allow definitive classification of
      the ovarian lesions, and we prefer at present to retain their current designation
      as a subtype of luteinized thecoma, but to allow for the possibility of a non
      neoplastic nature, feel it reasonable to have the designation "thecomatosis" as a
      parenthetical alternative. We have documented for the first time that sclerosing
      peritonitis is not invariably associated with the distinctive ovarian pathology
      present in these cases.

PMID- 18636019
TI  - Speed of mental operations in fibromyalgia: a selective naming speed deficit.
AB  - OBJECTIVE: Abnormal processing of information in fibromyalgia may hold clues to
      brain abnormalities in this illness. The purpose of this study is to examine the
      speed of mental operations in people with the fibromyalgia syndrome (FMS) under
      the pressure of time. The central question addresses whether FMS is associated
      with processing speed deficits across a spectrum of speeded tasks. METHODS: Sixty
      seven patients with fibromyalgia with a history of memory complaints and 51
      controls presenting with complaints of memory loss completed 10 timed cognitive
      measures of processing speed. Controls were patients with memory complaints who
      did not have FMS. RESULTS: The majority of FMS patients (>70%) performed within 1
      standard deviation of the norm on 7 or more of 10 speeded measures. However, more
      than 49% of FMS patients tested as impaired (>1.67 SD below normative mean) on 2
      specific validated speed tasks (reading words and naming colors). Compared with
      controls, the number of FMS patients showing impairment was 2.0 times greater for
      reading speed, and 1.6 times greater for color naming speed. A mean time delay of
      203 milliseconds was recorded for reading words and 285 milliseconds for naming
      colors in the FMS impaired sample. A 203 milliseconds delay in reading words
      represents a 48% (203/417) time increase over the normal time for reading the
      same stimulus word. CONCLUSION: Abnormalities in naming speed are an
      unappreciated feature of FMS. Selective deficits in naming speed in association
      with otherwise well preserved global processing speed set patients with FMS apart
      from controls with memory complaints. Clinicians would be wise to specifically
      request adding a rapid naming test such as the Stroop Test to the cognitive
      battery; to document cognitive dysfunction in FMS patients who otherwise appear
      to test normally, despite often intense complaints of memory and concentration
      difficulties that can affect job performance and increase disability.

PMID- 18636020
TI  - Adherence to medications in systemic lupus erythematosus.
AB  - BACKGROUND: Lack of adherence is a ubiquitous problem which can be a hindrance in
      the treatment of chronic conditions like systemic lupus erythematosus (SLE).
      OBJECTIVES: A random sample of 63 SLE patients attending rheumatology clinics
      associated with University Medical Centers were surveyed to measure level of
      adherence to their SLE medications and to identify the risk factors that have
      been associated previously with nonadherence to these medications. METHODS:
      Information on traditional SLE outcomes was obtained by face-to-face interviews
      and medical record review. Various patient proposed strategies were identified to
      improve adherence to these medications. RESULTS: When considering adherence
      estimates of > or =80% as representing sufficient adherence for achieving a
      therapeutic response, adherence to medications was only modestly adherent, likely
      limiting the effectiveness of the prescribed medication regimens. Based on
      pharmacy refill information 61% of the patients were sufficiently adherent to
      prednisone, 49% to hydroxychloroquine, and 57% to other immunosuppressant
      medications. Significant risk factors of insufficient adherence included being
      single, low educational level, presence of other comorbidities, limited
      comprehension of physician explanations and instructions, and having to take the
      medication more than one daily. Based on subject reports, busy life styles were
      among the most important barriers to adherence whereas pillboxes were considered
      most helpful for helping with medication adherence. CONCLUSION: Although lack of
      sufficient adherence to medications appears to be a multifactorial problem,
      improved communication between the healthcare provider and the patient, and less
      complicated medication regimens, may be especially suitable interventions to
      improve adherence to medications.

PMID- 18636021
TI  - Protracted febrile myalgia mimicking polyarteritis nodosa.
AB  - An insidious onset of unexplained fever, weight loss, skin lesions, abdominal
      pain, and musculoskeletal pain should suggest the diagnosis of polyarteritis
      nodosa (PAN). However, familial Mediterranean fever (FMF) with protracted febrile
      myalgia (PFM) should be kept in mind in the differential diagnosis. In this
      report, 6 cases of PFM mimicking PAN are described. Patients presented with
      severe muscle and abdominal pain lasting longer than 4 weeks. Their common
      medical history included recurrent febrile abdominal pain or arthritis. Physical
      examination revealed hypertension together with severe muscle tenderness.
      Laboratory examination revealed high acute phase reactants, negative p-ANCA,
      normal creatine kinase, and complement levels. Duplex abdominal ultrasonography
      was normal. Four of 6 patients were hospitalized with initial diagnoses of PAN.
      Renal and mesenteric angiography performed in 1 patient was normal. Steroid
      therapy controlled all the severe symptoms including hypertension in all of the
      cases.FMF with PFM is important in the differential diagnosis of patients with
      suspected vasculitis especially when myalgia is present. Hypertension may be
      present as a result of sympathetic discharge because of severe myalgia. Because
      PFM rapidly responds to a short course of corticosteroids, a rapid diagnosis of
      PFM in FMF patients can reduce unnecessary workup and decrease the time patients
      have to suffer.

PMID- 18636022
TI  - Transacromial extra-articular Knowles pin fixation treatment of acute type V
      acromioclavicular joint injuries.
AB  - BACKGROUND: Type V acromioclavicular (AC) joint dislocations need surgical
      treatment. This report described a new transacromial extra-articular Knowles pin
      fixation method to treat this very unstable dislocations to analyze this
      treatment. The hypothesis is that the results would be improved. METHOD: Thirteen
      consecutive patients with type V AC joint dislocations within 9 days of injuries
      were treated by open reduction transacromial extra-articular Knowles fixation, AC
      ligament repair, coracoclavicular (CC) ligament repair, CC augmentation sutures.
      All of them received postoperative arm sling supports for 3 weeks. The
      radiographic and clinical follow-up was at least 23 months. A modified Constant
      Murley score was used for evaluation of bilateral shoulder functions. RESULTS:
      All AC ligaments were torn at the clavicle sides. All CC ligament were torn at
      the mid-substances. The anterior deltoid insertions and the superior-posterior
      trapezius insertions to the clavicles were torn. Radio-lucent zones around the
      pins 1 mm to 3 mm were noted in all patients before pin removal. Lateral pin
      migration 1 mm to 2 mm were noted in nine patients before pin removal. Nine
      patients had increase of CC distances 1 mm to 4 mm at follow-up. Six patients had
      CC space calcifications. The mean modified Constant-Murley score of the injured
      shoulders was 94.5 +/- 2.7, the mean score of the uninjured shoulders was 93.9 +/
      1.3, which was not statistically different. CONCLUSIONS: The transacromial extra
      artocular Knowles pin fixation method is a reliable method to treat acute type V
      AC joint dislocations.

PMID- 18636023
TI  - Preemptive antibiotic treatment based on gram staining reduced the incidence of
      ARDS in mechanically ventilated patients.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the major
      complications in the intensive care unit. VAP sometimes results in acute
      respiratory distress syndrome (ARDS), and the associated mortality is high. We
      hypothesized that preemptive antibiotic therapy based on results of bedside gram
      staining would reduce the incidence of VAP. METHODS: Patients who were
      endotracheally intubated in our intensive care unit for more than 72 hours were
      included. Patients younger than 16 years of age or patients died because of brain
      death were excluded. The study was divided into two periods. During the first
      period, we used antibiotics according to the American Thoracic Society
      guidelines. During the second period, antibiotics were given according to the
      results of bedside gram staining even before radiographic infiltrate appeared.
      RESULTS: One hundred twenty-eight patients and 133 patients were included in the
      first and second periods, respectively. The incidence of VAP was significantly
      decreased in the second period (first period, 22%; second period, 9%, p < 0.01).
      The incidence of ARDS was also decreased significantly in the second period
      (first period, 11%; second period, 3%, p < 0.01). The duration and total amount
      of antibiotics administered did not increase in the second period. VAP associated
      mortality was significantly lower in the second period (first period, 5%; second
      period, 0.8%, p < 0.05). CONCLUSION: Early diagnosis and treatment of respiratory
      infection based on results of gram staining significantly reduced the incidences
      of VAP and ARDS without an increase in the use of antibiotics.

PMID- 18636024
TI  - The differences between venous air embolism and fat embolism in routine
      intraoperative monitoring methods, transesophageal echocardiography, and fatal
      volume in pigs.
AB  - BACKGROUND: Venous air embolism (VAE) or fat embolism (FE) may occur in similar
      clinical settings such as after multiple injuries or total hip replacement. We
      designed this study to observe the differences between VAE and FE in routine
      intraoperative monitoring methods, transesophageal echocardiography (TEE), and
      fatal volume in pigs. METHODS: Sixteen domestic pigs were randomly assigned to
      either a fat group (n = 8) or an air group (n = 8). Each animal was injected with
      a series of volumes of air or fat. TEE and routine intraoperative monitoring were
      used during the experiment. The echogenic pattern of air or fat emboli were
      recorded and was graded (grade 0, no emboli; grade 1, a few fine emboli; grade 2,
      embolic masses less than 5 mm in diameter and the right atrium opacified with
      echogenic materials; grade 3, fine emboli mixed with large embolic masses greater
      than 5 mm in diameter or serpentine emboli). Precordial auscultation was
      performed before and after each injection of air or fat. The fatal volumes of air
      and fat were recorded. RESULTS: No echogenic pattern grade 3 on TEE in the fat
      group was observed even fatal volume of fat was injected, whereas echogenic
      pattern grade 3 was found in all pigs in the air group when > or = 0.5 mg/kg of
      air was injected (0/8 vs. 8/8, p < 0.01). Paradoxical embolism and cutaneous
      petechiae was more common in the fat group than in the air group (8/8 vs. 1/8,
      6/8 vs. 0/8, p < 0.05). "Bubble-like" sounds, "drum-like" murmurs, and "mill
      wheel" murmurs were only heard in the air group but not in the fat group (8/8 vs.
      0/8, p < 0.01). Fatal volume of air was much higher than that of fat (4 mL/kg +/-
      0.76 mL/kg vs. 0.24 mL/kg +/- 0.05 mL/kg, p < 0.01). CONCLUSIONS: Large extensive
      echogenic masses on TEE, "bubble-like" sounds, "drum-like" murmurs, and "mill
      wheel" murmurs were more likely associated with VAE. All of fat emboli were fine
      on TEE. Paradoxical embolism and cutaneous petechiae were more common in FE.
      Fatal volume of fat is lower than that of air.

PMID- 18636025
TI  - Tumor necrosis factor alpha can induce recruitment of inflammatory cells to the
      cochlea.
AB  - HYPOTHESIS: Leukocyte recruitment to the cochlea can be induced by tumor necrosis
      factor alpha (TNF-alpha) at concentrations that are not cytotoxic to sensory
      cells in the organ of Corti. BACKGROUND: Leukocytes participating in inflammation
      enter the inner ear via the spiral modiolar vein and its tributaries. Many of the
      infiltrated leukocytes express TNF-alpha 3 hours after cochlear antigen challenge
      of systemically antigen-sensitized animals. Competitive inhibition of TNF-alpha
      receptors reduces inflammation and hearing loss in experimentally induced
      labyrinthitis in guinea pigs and mice. However, TNF-alpha is also potentially
      cytotoxic, acting through the external apoptotic pathway and TNF-alpha
      transmembrane, cell surface receptors. It may therefore also participate in the
      sensory cell degeneration resulting from inflammation. METHODS: To test for
      recruitment potential, TNF-alpha or phosphate-buffered saline was infused into
      the guinea pig inner ear for 2 to 4 days through a cochleostomy using an osmotic
      pump (0.2 or 2.0 microg/mL; 1 microL/h) or a bolus injection (50 microg/mL; 10
      microL). Auditory evoked brainstem response thresholds were measured before and
      after challenge, and cochleas were evaluated for the presence of leukocytes. To
      test for toxicity, organ of Corti explants were subjected to 3 concentrations of
      TNF-alpha (0.1, 10, and 1,000 ng/mL) for 96 hours, and the number of hair cell
      places was counted. RESULTS: Tumor necrosis factor alpha infused into the guinea
      pig cochlear scala tympani resulted in infiltration of leukocytes around the
      venules and within scala tympani. There was no associated hearing loss as
      measured with a click stimulus. Tumor necrosis factor alpha applied directly to
      organ of Corti explants caused minimal hair cell death at concentrations used in
      the in vivo experiments. At higher concentrations, there was 15 to 20% loss of
      cells. CONCLUSION: Tumor necrosis factor alpha is sufficient to recruit
      inflammatory cells to the cochlea but is not likely to be directly responsible
      for the hearing loss that follows immune-mediated labyrinthitis.

PMID- 18636026
TI  - Illness perceptions, coping, and quality of life in vestibular schwannoma
      patients at diagnosis.
AB  - OBJECTIVE: To evaluate illness perceptions, coping behavior, and quality of life
      (QOL) in patients with vestibular schwannoma (VS) at diagnosis. STUDY DESIGN:
      Prospective patient analysis. SETTING: University Teaching Hospital, tertiary
      care clinic. PATIENTS: Consecutive patients with VS (n = 80) completed a set of
      questionnaires at diagnosis to assess psychological characteristics and QOL.
      INTERVENTION: Diagnostic and rehabilitative. MAIN OUTCOME MEASURES: Psychological
      characteristics and QOL, measured via questionnaires focusing on illness
      perceptions (Illness Perception Questionnaire Revised), coping (Utrecht Coping
      List), and QOL (Medical Outcomes Study 36-Item Short Form Health Survey), were
      compared with normative data for the general Dutch population and to data
      concerning patients with other illnesses. RESULTS: The 36-Item Short Form Health
      Survey scores of VS patients at diagnosis were significantly decreased when
      compared with healthy controls, patients with head and neck cancer, benign
      prostate hypertrophy, chronic obstructive pulmonary disease, and deaf patients.
      Scores for illness perceptions were in between those of patients with acute pain
      and chronic pain for most subscales except illness identity, emotional
      representations, and illness coherence. In their coping behavior, VS patients
      scored lower on the subscale active coping, sought less social support, and
      expressed their emotions less, but also showed less passive coping compared with
      reference values. CONCLUSION: Vestibular schwannoma patients experience impaired
      QOL compared with healthy controls and reference groups. Their illness
      perceptions are in between those of patients with acute and chronic pain, and
      their coping behavior is less active in general. This may have implications for
      clinical decision making and for optimizing interaction with patients. Changing
      illness perceptions and coping by means of an intervention and encouraging social
      support by means of patient support groups may improve QOL in VS patients.

PMID- 18636027
TI  - BAHA devices and magnetic resonance imaging scanners.
AB  - HYPOTHESIS: That an osteointegrated Bone-anchored Hearing Aid (BAHA System) will
      show movement or displacement when exposed to a 9.4-T magnetic resonance imaging
      (MRI) magnet and that any movement may have implications for patient safety and
      image quality. BACKGROUND: BAHA System implanted patients may require MRI scans
      for various pathologies. The possibility of BAHA fixture and abutment movement
      can be explored to help clarify patients' and physicians' decisions regarding
      safety issues. SETTING: University Medical Center (tertiary care center).
      METHODS: BAHA System assembled fixture with abutment of 3 and 4 mm were each
      placed inside of a Petri dish and mounted into human cadaver temporal bones, then
      exposed to a 9.4-T MRI magnet. The BAHA System external processor was entered
      into the MRI suite. Head MRI images and charts of 2 patients with BAHA System
      devices who had undergone MRI scanning at 1.5 and 3.0 T, respectively, were
      reviewed. RESULTS: The BAHA System fixture with abutment moved inside of the
      Petri dish. The temporal bone studies revealed no sign of motion or displacement.
      The external BAHA processor showed strong movement toward the magnet. MRI
      scannings of patients were without any adverse effects. Image MRI quality was
      affected only around the BAHA post. CONCLUSION: The bone-mounted fixture with
      abutment of 3 and 4 mm resisted any magnetic forces trying to displace them up to
      9.4 T. Two patients underwent scanning at 1.5 and 3.0 T with no adverse effects.
      MRI image quality was excellent starting at 1 cm from the fixture with abutment.
      The study findings lend strong evidence that patients can be safely scanned up to
      9.4 T without adverse effects.

PMID- 18636028
TI  - New macroscopic classification of stapedio-ovalar otosclerosis: a simplified
      rating for training in stapedotomy.
AB  - OBJECTIVE: To have a new macroscopic classification of otosclerosis based on
      appearance variations of the stapes footplate due to the disease and to determine
      if the color variations are correlated to a minor or major incidence of footplate
      complications. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: From
      January 2006 to December 2006, 106 patients affected by otosclerosis underwent
      surgery. Three revision procedures (1 primarily operated in our department and 2
      elsewhere) were excluded from the study. We finally considered 103 surgical
      procedures. In all patients, the appearance of stapes footplate before removing
      superstructure was assessed to determine a simplified rating of stapedial
      otosclerosis. We then excluded from the study group 7 patients in which the
      footplate was not visible (obliterative otosclerosis). Finally, we considered 96
      otosclerosis patients divided into 2 groups (Groups A and B) that differed only
      in footplate color. Group A included 74 otosclerosis patients with blue footplate
      (77%), and Group B included 22 otosclerosis patients with white footplate (23%).
      We planned a stapedotomy procedure for all patients of Groups A and B. The
      surgeon, anesthesia, approach, succession of surgical steps, and type of surgical
      instruments were the same in all patients. We estimated whether there is
      statistical correlation between the incidence of footplate complications
      (floating footplate and footplate fracture) and the color variations of the
      stapes footplate in Groups A and B. MAIN OUTCOME MEASURES: Color footplate,
      incidence of footplate complications (floating and fractures footplate). RESULTS:
      The visible portion of stapes footplate before removing superstructure preserves
      the natural blue color in all its points in 71.84% of patients (n = 74). In
      21.36% of patients (n = 22), the footplate appears white in all or in most of its
      extent. In 6.8% of patients (n = 7), the footplate was not visible because it was
      covered by massive otospongiotic tissue. Comparison of incidence of footplate
      complications between Groups A and B showed statistical significance. The
      incidence of footplate complications is higher in white otosclerosis than in blue
      otosclerosis. CONCLUSION: Based on the appearance and, furthermore, on the color
      of the visible portion of stapes footplate, before removing superstructure, the
      authors have formulated a new classification of otosclerosis: blue otosclerosis
      (blue footplate), white otosclerosis (white footplate), and obliterative
      otosclerosis (nonvisible footplate). The advantage of this classification is that
      it consents, before making any manipulation on the stapes, a rapid and simple
      identification of the different degrees of difficulty of surgery: I degree, blue
      otosclerosis; II degree, white otosclerosis; and III degree, obliterative
      otosclerosis.

PMID- 18636029
TI  - Imaging characteristics of metastatic lesions to the cerebellopontine angle.
AB  - OBJECTIVE: To describe characteristic features of metastatic lesion to the
      cerebellopontine angle (CPA) and internal auditory canal (IAC). STUDY DESIGN:
      Retrospective review. SETTING: Tertiary care medical center. PATIENTS: Patients
      with metastatic lesions to the CPA. INTERVENTION: Diagnostic. MAIN OUTCOME
      MEASUREMENTS: Clinical presentation and imaging characteristics on magnetic
      resonance imaging and computed tomography. RESULTS: A total of 25 cases were
      reviewed. The average patient age was 56 years, and almost all patients presented
      with palsy of the cranial VII and VIII nerves. There were 14 cases of metastases
      to the CPA, 16 cases to the IAC, 5 cases to the CPA and IAC, and 7 cases to the
      dura. There were several identifiable patterns of metastases to the CPA/IAC,
      including the flocculus (5), pia/arachnoid (12), dura (7), and choroid plexus
      (3). T1 magnetic resonance imaging was most commonly isointense to hypointense to
      brain, with enhancement on T1 imaging with contrast. Lesions tend to be eccentric
      to the IAC. T2 and fluid-attenuated inversion-recovery (FLAIR) imaging shows
      adjacent cerebellar and brainstem vasogenic edema. Characteristics that
      differentiate metastatic lesions from benign lesions of the CPA include vasogenic
      edema on T2 and FLAIR imaging and multiple central nervous system lesions and
      lesions that are eccentric to the IAC. CONCLUSION: Recognizing characteristic
      patterns of spread to the CPA and IAC can aid the clinician in the diagnosis of
      metastatic lesions to this area. Clinical history of rapidly progressive cranial
      nerve deficits, particularly facial paralysis in a patient with a history of
      malignancy, increases the level of suspicion. Imaging characteristics of
      metastatic lesions to the CPA include adjacent vasogenic edema observed on T2
      weighted imaging and FLAIR, eccentric location to the IAC, and multiple lesions
      observed on head and neck imaging.

PMID- 18636030
TI  - Malignant melanoma metastasis to temporal bone.

PMID- 18636031
TI  - The investigation of the recurrence rate of cholesteatoma using Kaplan-Meier
      survival analysis.
AB  - OBJECTIVES: To investigate the recurrence rate of cholesteatoma using Kaplan
      Meier survival analysis. STUDY DESIGN: Retrospective study. SETTING: Tertiary
      referral center. PATIENTS: Three hundred forty-five patients with middle ear
      cholesteatoma operated on by the same surgeon between 1987 and 2002. METHODS: The
      cumulative recurrence rate of cholesteatoma during a 5-year follow-up period was
      calculated using Kaplan-Meier survival analysis. RESULTS: The overall 5-year
      recurrence rate was 11.8%. The recurrence rate increased with the follow-up time.
      The 5-year recurrence rate was 3.9% in patients treated with canal wall down
      tympanoplasty (CWDT) and 16.7% in patients treated with intact canal wall
      tympanoplasty (ICWT) or canal wall reconstruction (CWR) after CWDT with a
      significant difference (p < 0.01). The 5-year recurrence rate was 26.0% in
      patients operated on between 1987 and 1996 and 0.7% in patients operated on
      between 1997 and 2002, again with a significant difference (p < 0.001).
      CONCLUSION: Kaplan-Meier survival analysis should be used for calculating the
      recurrence rate of cholesteatoma. Although this analytic method further
      demonstrates that CWDT is a more reliable surgical method than ICWT/CWR in
      reducing cholesteatoma recurrence, clinical judgment should be exercised, and we
      continue to recommend that a flexible approach should be adopted in deciding
      whether to perform CWDT or ICWT/CWR for individual cases.

PMID- 18636032
TI  - Risk factors of sensorineural hearing loss in patients with ischemic stroke.
AB  - OBJECTIVES: We investigated risk factors of sensorineural hearing loss (SHL) in
      patients with early stage of ischemic stroke (IS). METHODS: Our study consisted
      of 60 patients with IS who were treated at Department of Neurology, Medical
      University of Gdansk between 2006 and 2007. A multivariate stepwise linear
      regression was used to identify the risk factors that were related to SHL as
      measured by pure-tone average (0.5, 1, and 2 kHz), the high-tone average (4, 6,
      and 8 kHz), the pure-tone middle-tone average (0.5, 1, 2, and 4 kHz), and the
      overall average (0.5, 1, 2, 4, 6, and 8 kHz). The following factors were included
      in the analysis: age, sex, smoking habit, addiction to alcohol, presence of
      tinnitus and vestibular symptoms, arterial hypertension, cardiac ischemic
      disease, hyperlipidemia, diabetes, number of risk factors, neurologic state at
      the admission, localization of stroke, cause of stroke, number of ischemic
      focuses, the side and diameter of ischemic focuses, the result of directional
      hearing acuity angle test, results of certain laboratory tests, blood morphology
      parameters, and coagulogram. Values for p less than 0.05 were considered
      significant. RESULTS: Our analysis suggests the presence of the following risk
      factors of SHL in patients with IS: 1) older age (>60 yr); 2) male sex; 3)
      presence of tinnitus; 4) arterial hypertension; 5) lacunar type of stroke; 6)
      presence of multiple ischemic focuses; 7) presence of bilateral ischemic focuses;
      8) changes in blood cell count; and 9) disturbances of agglutination. CONCLUSION:
      The highest risk of hearing loss in the group of IS patients occurred at older
      people, particularly men with tinnitus, lacunar stroke, multiple, bilateral
      ischemic focuses, and arterial hypertension. A negative statistically significant
      influence of decreased level of red cells, platelets, and hematocrit value on
      hearing loss was found. Abnormally lowered levels of activated partial
      thromboplastin time, activated partial thromboplastin time ratio, prothrombin
      index, and abnormal lowered level of international normalized ratio statistically
      impaired hearing.

PMID- 18636034
TI  - Vestibular schwannoma: an understanding of growth should influence management
      decisions.
AB  - BACKGROUND: Treatments for vestibular schwannomas include surgical removal and
      radiotherapy. Observation is a reasonable alternative, given the slow growth of
      these tumors. The goal of this study was to determine the 5-year no-growth rate
      in patients managed initially by observation in attempts to define indications
      for treatment. STUDY DESIGN: Retrospective chart analysis of prospectively
      collected patient database. METHODS: Patients with unilateral vestibular
      schwannomas who presented in the last 10 years were reviewed. Those managed
      initially by observation were reviewed. At least 2 consecutive imaging studies
      were required. The following information was recorded from the charts: age, sex,
      tumor size at presentation and subsequent follow-up sessions, treatment in the
      event of growth, and time interval between presentation and last imaging
      available. The institutional ethics committee approved the study. RESULTS: One
      hundred ten patients were included. There were 65 male patients and 45 female
      patients. The mean age was 62.4 years (range, 32-91 yr). The mean follow-up was
      31.4 months (range, 6-156 mo). Twenty-three patients demonstrated evidence of
      growth, with an overall 5-year no-growth rate of 70.6%. Despite growth, the 5
      year no-intervention rate was 81.3%. Interestingly, 11 patients (10%)
      demonstrated tumor regression. Patients with intracanalicular tumors had a 5-year
      no-growth rate of 89.8% compared with 73.9% and 45.2% for Grade I and Grade II or
      larger tumors, respectively. The difference between intracanalicular and Grade II
      or larger tumors was statistically significant (p = 0.0196). CONCLUSION: Our data
      suggest that treatment can be delayed in a large proportion of vestibular
      schwannoma patients and that this is particularly true in patients with small
      tumors. Despite growth, only a small percentage of patients require intervention.
      Thus, we recommend a period of observation to determine the need for treatment in
      patients without indications for urgent intervention.

PMID- 18636035
TI  - Linearity and lever ratio of the normal and reconstructed cadaveric human middle
      ear.
AB  - HYPOTHESIS: The linearity and the level ratio are different in reconstructed
      ears. BACKGROUND: The linearity of the reconstructed human middle ear (ME) has
      not been previously explored. It is important to analyze if high sound pressure
      levels (SPLs) result in distortion due to nonlinearities particularly because
      hearing aids have high-output SPLs. The diseased ME is reconstructed with
      prostheses. These diseased ears frequently need additional amplification with
      hearing aids, and it is unclear if reconstruction itself leads to nonlinear ME
      responses. METHODS: Eight fresh human cadaveric temporal bones were used. Pure
      tones of 70, 90, and 110 dB SPL at 500, 1,000, and 3,000 Hz were presented to the
      ear canal. Umbo and stapes displacements were measured by means of a laser
      Doppler vibrometer. After removing the incus, the tympanic membrane assembly to
      the stapes head prosthesis was placed, and measurements were repeated. RESULTS:
      Stapes footplate vibrations in the reconstructed ears are 10 to 15 dB lower than
      those of the normal ears. In both normal and reconstructed ears, the footplate
      vibrations are linearly related to SPL at the tympanic membrane between 70 and
      110 dB SPL at the frequencies tested. For the lever ratio, intact ears are more
      efficient at transmission of umbo vibrations to the stapes compared with
      reconstructed ears. CONCLUSION: To within acceptable limits, the ME seems to be
      linear between 70 and 110 dB SPL input levels, across the speech frequencies, and
      this does not change with reconstruction. The reconstructed human ME seems to
      have a less efficient lever ratio than the intact ME.

PMID- 18636036
TI  - Prognostic value of initial electronystagmography findings in idiopathic sudden
      sensorineural hearing loss without vertigo.
AB  - OBJECTIVE: We used electronystagmography (ENG) to characterize recurrent hearing
      loss and its progression to definite Meniere's disease in patients with
      idiopathic sudden sensorineural hearing loss (SSHL) without subjective vertigo.
      METHODS: We reviewed medical records of 1,334 patients with unilateral hearing
      loss initially diagnosed with idiopathic SSHL between 1985 and 2003 at our
      university hospital. Of the 1,334 patients, we examined 127 (86 with low-tone and
      41 with high-tone SSHL) who underwent ENG within 30 days of the initial diagnosis
      and who could be followed up during the long term. RESULTS: Spontaneous nystagmus
      (SN) was observed in approximately half of the vertigo-unaccompanied group. Long
      term follow-up with a mean of 67 months revealed that the recurrence rate of
      hearing loss was 51.2% in low-tone SSHL patients with SN. The recurrence rate of
      hearing loss was 27.9% in low-tone SSHL patients without SN. Progression to
      Meniere's disease occurred in 14.0% of the low-tone-type and 12.5% of the high
      tone-type patients when SN was detected. In contrast, in both the low-tone-type
      and high-tone-type groups, none developed Meniere's disease when SN was absent.
      CONCLUSION: Our results suggest that the initial ENG findings could provide
      prognostic information for idiopathic SSHL patients, even those who have no
      vestibular symptoms at the first visit.

PMID- 18636038
TI  - A bird's eye view of enteric nervous system development: lessons from the avian
      embryo.
AB  - The avian embryo has been an important model system for studying enteric nervous
      system (ENS) development for over 50 y. Since the initial demonstration in chick
      embryos that the ENS is derived from the neural crest, investigators have used
      the avian model to reveal the cellular origins and migratory pathways of enteric
      neural crest-derived cells, with more recent work focusing on the molecular
      mechanisms regulating ENS development. Seminal contributions have been made in
      this field by researchers who have taken advantage of the strengths of the avian
      model system. These strengths include in vivo accessibility throughout
      development, ability to generate quail-chick chimeras, and the capacity to
      modulate gene expression in vivo in a spatially and temporally targeted manner.
      The recent availability of the chicken genome further enhances this model system,
      allowing investigators to combine classic embryologic methods with current
      genetic techniques. The strengths and versatility of the avian embryo continue to
      make it a valuable experimental system for studying the development of the ENS.

PMID- 18636037
TI  - The ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular
      schwannoma xenografts in nude mice: a preliminary study.
AB  - OBJECTIVE: To analyze the ability of ErbB inhibitors to reduce the growth of
      vestibular schwannoma (VS) xenografts. METHODS: Vestibular schwannoma xenografts
      were established in the interscapular fat pad in nude mice for 4 weeks.
      Initially, a small cohort of animals was treated with the ErbB2 inhibitor
      trastuzumab or saline for 2 weeks. Animals also received bromodeoxyuridine
      injections to label proliferating cells. In a longer-term experiment, animals
      were randomized to receive trastuzumab, erlotinib (an ErbB kinase inhibitor), or
      placebo for 12 weeks. Tumor growth was monitored by magnetic resonance imaging
      during the treatment period. Cell death was analyzed by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin end labeling of fragmented DNA. RESULTS: Tumors
      can be distinguished with T2-weighted magnetic resonance imaging sequences.
      Trastuzumab significantly reduced the proliferation of VS cells compared with
      control (p < 0.01) as analyzed by bromodeoxyuridine uptake. Control tumors
      demonstrated slight growth during the 12-week treatment period. Both trastuzumab
      and erlotinib significantly reduced the growth of VS xenografts (p < 0.05).
      Erlotinib, but not trastuzumab, resulted in a significant increase in the
      percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end
      labeling of fragmented DNA-positive VS cells (p < 0.01). CONCLUSION: In this
      preliminary study, the ErbB inhibitors trastuzumab and erlotinib decreased growth
      of VS xenografts in nude mice, raising the possibility of using ErbB inhibitors
      in the management of patients with schwannomas, particularly those with
      neurofibromatosis Type 2.

PMID- 18636039
TI  - The effect of hypoxia, reoxygenation, ischemia, and reperfusion on hydraulic
      permeability in rat mesenteric venules.
AB  - Little is known regarding the effects of I/R on hydraulic permeability (Lp). We
      sought to compare the individual influences of hypoxia, ischemia, reoxygenation,
      and reperfusion on Lp. We hypothesized that (1) hypoxia increases Lp; (2)
      reoxygenation further increases Lp; (3) ischemia results in greater increases in
      Lp compared with hypoxia; (4) reperfusion causes additional increases in Lp
      compared with hypoxia, ischemia, and reoxygenation; and (5) xanthine oxidase (XO)
      and white blood cell adherence play important roles in hypoxia, ischemia, and
      reperfusion. Hydraulic permeability was measured by an in vivo microcannulation
      technique during hypoxia, reoxygenation, ischemia, and reperfusion in rat
      mesenteric postcapillary venules. Additional rats were fed a Tungsten-enriched
      diet to inhibit XO activity, and the studies were repeated. White blood cell
      adherence was also documented. Hypoxia and ischemia both increased Lp 2-fold from
      baseline levels (P < 0.001). Reoxygenation did not alter Lp compared with 15 min
      of hypoxia alone (P > 0.07). Reperfusion after hypoxia increased Lp 6-fold (P <
      0.001). Reperfusion after ischemia also increased Lp 6-fold (P < 0.001).
      Inhibition of XO had no effect on the increase in Lp after both hypoxia and
      ischemia. However, inhibition of XO attenuated the 6-fold increase in Lp observed
      during reperfusion after both hypoxia and ischemia by approximately 50% (P <
      0.001). White blood cell adherence increased during reperfusion but not hypoxia
      or ischemia. The complexity of I/R injury makes it a difficult clinical scenario
      to model for research. We have demonstrated in an in vivo model that hypoxia and
      ischemia increase Lp similarly, and that reperfusion has a profound deleterious
      effect on Lp. These changes in Lp seem to be XO and white blood cell dependent.

PMID- 18636040
TI  - Inflammation-induced hepatotoxicity in humans.
AB  - Because severe sepsis is frequently complicated by multiple organ failure, it is
      of importance to monitor organ function. Unfortunately, conventional liver
      function markers are either relatively unspecific or have a long half-life, which
      make them poor predictors of acute liver injury. Glutathione S-transferase A1-1
      (GSTA1-1) has a relatively short half-life (1 h), is more specific, and is
      rapidly released into the blood after liver damage. In the present study, we
      measured plasma GSTA1-1 levels by enzyme-linked immunosorbent assay in seven
      healthy volunteers after repeated experimental endotoxemia induced by 2 ng kg
      Escherichia coli endotoxin per day (to investigate inflammation-induced hepatic
      injury) and in 21 patients within 12 h after the occurrence of severe
      sepsis/septic shock (to investigate its ability to predict an increase of
      transaminases on day 7). During repeated experimental endotoxemia in healthy
      volunteers, TNF-alpha and IL-6 levels increased from undetectable levels to 1,425
      (474-1,949) and 1,739 (989-2,047) pg mL, respectively, whereas GSTA1-1 levels did
      not exceed the normal range, indicating that no (sub)clinical liver injury occurs
      in this model of inflammation. In septic patients, GSTA1-1 levels had a
      specificity of 88%, resulting in a positive predictive value for liver injury of
      86% and a positive likelihood ratio of 6 to indicate an increase in transaminases
      on day 7. Furthermore, GSTA1-1 levels did not correlate with IL-6 levels but did
      with dobutamine infusion rate (Spearman r = 0.94; P = 0.02), suggesting that the
      extent of hemodynamic instability and not the degree of inflammation could be of
      importance for the occurrence of liver damage. In septic shock patients, GSTA1-1
      may represent a useful marker for early liver injury.

PMID- 18636041
TI  - Scoring systems for prediction of mortality in patients with intensive care unit
      acquired sepsis: a comparison of the Pitt bacteremia score and the Acute
      Physiology and Chronic Health Evaluation II scoring systems.
AB  - This study compares the effectiveness of the Pitt bacteremia score, the Charlson
      weighted index of comorbidity, and the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) scoring systems for the prediction of mortality in
      intensive care unit (ICU) patients with sepsis using the retrospective
      observational method on 134 patients with ICU-acquired sepsis. The statistical
      analyses show several important findings. First, Pitt bacteremia score is
      significantly correlated with the APACHE II scoring system (correlation
      coefficient = 0.738, P < 0.001). Second, the APACHE II scoring system, the Pitt
      bacteremia score, and the Charlson weighted index of comorbidity are
      independently correlated with mortality. Third, the Pitt bacteremia score and the
      APACHE II scores are positively related to mortality in patients with ICU
      acquired sepsis. As the result of the analyses, the mortality rate in patients
      with sepsis in the ICU is better predicted with the Pitt bacteremia score because
      it provides better estimation of sensitivity and specificity than the APACHE II
      scoring system and the Charlson weighted index of comorbidity.

PMID- 18636042
TI  - The effect of anticoagulants and the role of thrombin on neutrophil-endothelial
      cell interactions in septic shock.
AB  - To examine the effects of anticoagulants and the role of thrombin on neutrophil
      platelet-endothelial cell interactions in septic shock. Controlled experiments
      using phase-contrast microscopy to study neutrophil, platelet, and endothelial
      cell interactions in flowing cell suspensions under simulated physiologic
      conditions. University research laboratory. Adult patients with septic shock and
      normal volunteers. Microslides were coated with human umbilical vein endothelial
      cells. Neutrophils and platelets removed from control subjects were stimulated
      with plasma from patients in septic shock and perfused over endothelial cells.
      Heparin (H), argatroban (A), antithrombin III (ATIII), and recombinant human
      activated protein C (rhAPC) with and without thrombin were added to cells
      suspended in septic plasma and normal plasma. The number of neutrophils adherent
      to endothelial cells, neutrophil rolling velocity, and the number of neutrophils
      in aggregates were determined. Flow cytometric analysis of cells was used to
      identify cell activation and the formation of platelet-neutrophil aggregates.
      Heparin, A, ATIII, rhAPC all significantly decreased neutrophil adhesion and
      aggregation, and increased rolling velocity of neutrophils suspended in septic
      plasma. These results are similar to those observed with normal plasma but
      present greater absolute changes. Platelet-neutrophil aggregation, platelet
      activation, and neutrophil activation were significantly decreased by each of the
      anticoagulants. The addition of thrombin to cell suspensions containing
      anticoagulants reversed the effects of H, A, ATIII, rhAPC on neutrophil adhesion,
      adherence, and rolling velocity. In addition, thrombin attenuated the effects of
      each of these agents on platelet-neutrophil aggregation, platelet activation, and
      neutrophil activation. These data suggest that H, A, ATIII, and rhAPC decrease
      sepsis-induced neutrophil-endothelial cell interactions. The reversal of this
      effect by thrombin suggests that these agents alter neutrophil-endothelial
      interactions through their anticoagulant effects and the resulting decrease in
      thrombin activity.

PMID- 18636043
TI  - beta-Blockers in sepsis: reexamining the evidence.
AB  - Sepsis remains the leading cause for noncardiac intensive care unit deaths in the
      United States. Despite recent advances in the treatment of this devastating
      condition, mortality and morbidity remain unacceptably high. Sepsis is
      characterized by a multitude of pathophysiological changes that include
      inflammation, metabolic derangements, hemodynamic alterations, and multiorgan
      dysfunction. Unfortunately, several studies of treatment modalities aimed at
      correcting one or more of the underlying derangements have led to disappointing
      results. New treatment modalities are needed. beta-Receptor blockers have long
      been used for a variety of conditions such as coronary artery disease, congestive
      heart failure, and arterial hypertension. Recent data suggest that beta-blocker
      effects on metabolism, glucose homeostasis, cytokine expression, and myocardial
      function may be beneficial in the setting of sepsis. Although treating a
      potentially hypotensive condition with a drug with antihypertensive properties
      may initially seem counterintuitive, the metabolic and immunomodulatory
      properties of beta-blockers may be of benefit. It is the purpose of this review
      to discuss the effects of beta-blockers on the following: (1) metabolism, (2)
      glucose regulation, (3) the inflammatory response, (4) cardiac function, and (5)
      mortality in sepsis.

PMID- 18636044
TI  - Anti-apoptotic and anti-inflammatory effects of hydrogen sulfide in a rat model
      of regional myocardial I/R.
AB  - Hydrogen sulfide (H2S) is a novel gaseous mediator produced by cystathionine-beta
      synthase and cystathionine-gamma-lyase in the cardiovascular system, including
      the heart. Using a rat model of regional myocardial ischemia/reperfusion, we
      investigated the effects of an H2S donor (sodium hydrogen sulfide [NaHS]) on the
      infarct size and apoptosis caused by ischemia (25 min) and reperfusion (2 h).
      Furthermore, we investigated the potential mechanism(s) of the cardioprotective
      effect(s) afforded by NaHS. Specifically, we demonstrate that NaHS (1) attenuates
      the increase in caspase 9 activity observed in cardiac myocytes isolated from the
      area at risk (AAR) of hearts subjected in vivo to regional myocardial I/R and (2)
      ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat
      hearts subjected to regional myocardial I/R. The cardioprotective effects of NaHS
      were abolished by 5-hydroxydeconoate, a putative mitochondrial adenosine
      triphosphate-sensitive potassium channel blocker. Furthermore, NaHS attenuated
      the increase in the I/R-induced (1) phosphorylation of p38 mitogen-activated
      protein kinase and Jun N-terminal kinase, (2) translocation from the cytosol to
      the nucleus of the p65 subunit of nuclear factor-kappaB, (3) intercellular
      adhesion molecule 1 expression, (4) polymorphonuclear leukocyte accumulation, (5)
      myeloperoxidase activity, (6) malondialdehyde levels, and (7) nitrotyrosine
      staining determined in the AAR obtained from rat hearts subjected to regional
      myocardial I/R. In conclusion, we demonstrate that the cardioprotective effect of
      NaHS is secondary to a combination of antiapoptotic and anti-inflammatory
      effects. The antiapoptotic effect of NaHS may be in part due to the opening of
      the putative mitochondrial adenosine triphosphate-sensitive potassium channels.

PMID- 18636045
TI  - Polymerized bovine hemoglobin can improve small-volume resuscitation from
      hemorrhagic shock in hamsters.
AB  - Systemic and microvascular hemodynamic responses to hemorrhagic shock volume
      resuscitation with hypertonic saline followed by infusion of polymerized bovine
      hemoglobin (PBH) at different concentrations were studied in the hamster window
      chamber model to determine the role of plasma oxygen-carrying capacity and
      vasoactivity during resuscitation. Moderate hemorrhagic shock was induced by
      arterial controlled bleeding of 50% of blood volume (BV), and a hypovolemic state
      was maintained for 1 h. Volume was restituted by infusion of hypertonic saline
      (7.5% NaCl), 3.5% of BV, followed by 10% of BV of PBH at 2 different
      concentrations. Resuscitation was followed for 90 min and was carried out using
      13 gPBH/dL (PBH13), PBH diluted to 4 gPBH/dL in albumin solution at matching
      colloidal osmotic pressure (PBH4), and an albumin-only solution at matching
      colloidal osmotic pressure (PBH0). Systemic parameters, microvascular
      hemodynamics, and functional capillary density were determined during hemorrhage,
      hypovolemic shock, and resuscitation. The PBH13 caused higher arterial pressure
      without reverting vasoconstriction and hypoperfusion. The PBH4 and PBH0 had lower
      MAP and partially reverted vasoconstriction. Only treatment with PBH4 restored
      perfusion and functional capillary density when compared with PBH13 and PBH0.
      Blood gas parameters and acid-base balance recovered proportionally to
      microvascular perfusion. Tissue PO2 was significantly improved in the PBH4 group,
      showing that limited restoration of oxygen-carrying capacity is beneficial and
      compensates for the effects of vasoactivity, a characteristic of molecular
      hemoglobin solutions proposed as blood substitutes.

PMID- 18636046
TI  - Comparison of the effects of aging and IL-6 on the hepatic inflammatory response
      in two models of systemic injury: scald injury versus i.p. LPS administration.
AB  - Regardless of age, a marked elevation in circulating IL-6 levels correlates with
      increased mortality after injury or an inflammatory challenge. We previously
      reported that aged IL-6 knockout mice given LPS have improved survival and
      reduced inflammatory response than LPS-treated aged wild type (WT) mice. Herein,
      we analyzed the effects of aging and IL-6 on the hepatic inflammatory response in
      two models of systemic injury: dorsal scald (burn) injury versus intraperitoneal
      LPS administration. At 24 h after burn injury, circulating alanine
      aminotransferase and hepatic neutrophil accumulation were comparable regardless
      of age or IL-6 deficiency. However, at this same time point, these indicators of
      liver damage, in addition to hepatic levels of KC, a neutrophil chemoattractant,
      were increased in aged WT mice given LPS relative to young WT mice given LPS. The
      hepatic injury was drastically reduced in aged IL-6 knockout mice given LPS as
      compared with LPS-exposed aged WT mice. Our results suggest that the nature of
      the insult will determine the degree of remote injury in aged animals. In
      addition, the role of IL-6 as a contributing factor of tissue injury may be
      insult specific.

PMID- 18636048
TI  - Animal models for trauma research: what are the options?
AB  - Even if trauma patients initially avoid death after trauma (due to massive blood
      volume loss, primary severe brain injury), they are still at risk for multiple
      organ failure. Thus, it is crucial to elucidate the underlying pathophysiological
      mechanisms of trauma/hemorrhagic shock and the immune response involved. As of
      now, many hemorrhagic shock/trauma studies have used various types of animal
      models. Despite a large number of results from these efforts, some authors have
      argued that animal model results are difficult to translate directly into the
      clinical scenario. This review summarizes the advantages and the disadvantages of
      using animal models in trauma/hemorrhagic shock studies and discusses the
      relevance of various animal studies to the clinical scenario.

PMID- 18636047
TI  - Aging and animal models of systemic insult: trauma, burn, and sepsis.
AB  - In the acute-care setting, it is widely accepted that elderly patients have
      increased morbidity and mortality compared with young healthy patients. The
      reasons for this, however, are largely unknown. Although animal modeling has
      helped improve treatment strategies for young patients, there are a scarce number
      of studies attempting to understand the mechanisms of systemic insults such as
      trauma, burn, and sepsis in aged individuals. This review aims to highlight the
      relevance of using animals to study the pathogenesis of these insults in the aged
      and, despite the deficiency of information, to summarize what is currently known
      in this field.

PMID- 18636049
TI  - The role of surgery when endovascular treatment is considered the first choice
      therapy for ruptured intracranial aneurysms.
AB  - AIM: Nowadays endovascular therapy is more and more considered as first choice
      treatment for ruptured intracranial aneurysms. The aim of this study was to
      understand the impact that endovascular treatment (EVT), chosen as first
      therapeutic strategy, has had in the selection of ruptured intracranial aneurysms
      submitted to surgery at our Institution and what role neurosurgeons still play in
      this setting. METHODS: From 1998 to 2002, 272 consecutive patients were treated
      at the Hospital of Toulouse for ruptured intracranial aneurysms: 222 by
      embolization and 50 by surgery. The two groups were homogeneous for sex, age and
      aneurysms multiplicity. RESULTS: The patients of the surgical group had a worst
      clinical-radiological status at the treatment time than those treated by EVT.
      Clipping was performed for different reasons: 16% for failure of attempted EVT;
      32% for intracranial hematoma requiring surgical evacuation; 30% for aneurysm
      morphology unsuitable for EVT and 22% for absence of the endovascular operator.
      Aneurysms of the middle cerebral artery (MCA) represented the main surgical
      group. The aneurysms judged unsuitable for EVT and addressed to surgery had often
      a complex morphology representing a challenge also for surgery. Mid-term outcome
      is significantly better for patients treated by EVT. CONCLUSION: The results show
      that microsurgery continues to have a role in the treatment of ruptured
      intracranial aneurysms even when EVT is the first choice. The precarious clinical
      conditions of the patients submitted to surgery and the frequent complexity of
      their aneurysms explain their worst outcome. This would advise training dedicated
      vascular Neurosurgeons to guaranty a high level treatment when EVT is not
      possible.

PMID- 18636050
TI  - Sectioning of filum terminale externum using a rigid endoscope through the sacral
      hiatus. Cadaver study.
AB  - AIM: Tethered cord syndrome (TCS) is a stretch-induced functional disorder of the
      spinal cord, which is directly related to filum fixation. Classic surgical
      approaches to the filum involve open surgery and include varying amounts of
      spinal bone removal. In an effort to reduce the morbidity and mortality of these
      procedures, the authors explored a less invasive method. They evaluated the
      ability, safety and feasibility for endoscopic sectioning of the filum terminale
      externum by performing upward orientated navigation in the extradural sacral
      spinal canal through the sacral hiatus using a rigid endoscope. METHODS: Four
      adult, phenol-formalin embalmed cadavers were used for endoscopic section of the
      filum terminale externum at the tip of thecal sac. After preparing the anatomical
      area of sacral hiatus, a rigid endoscope (Storz, of 3.8 mm external diameter with
      two working channels, of 1 mm each, one for suction-irrigation and one as
      working) was inserted into the extradural sacral spinal canal and the filum
      terminale externum was identified and cut easily at the distal end of thecal sac
      at the level of S2. In all cases, it was possible to manipulate the rigid
      endoscope and inspect the full length of the extradural sacral spinal canal,
      especially at the S1-S2 level. RESULTS: The results indicate that the tested
      transhiatal approach for upward orientated extradural endoscopy represents a
      minimally invasive procedure that provides an appropriate and feasible route to
      the extradural sacral spinal canal. CONCLUSION: Such approach is an attractive
      alternative for filum terminale externum sectioning in cases where tethered cord
      syndrome is not accompanied by any other pathology. Moreover if filum terminale
      internum sectiong is indicated, it can be performed in second stage.

PMID- 18636051
TI  - Five-level one-piece laminoplasty for extensive tumors of the lumbar spine.
AB  - The authors describe the surgical method and results of nonexpansive one-piece
      multivel laminoplasty of the whole lumbar spine, for microsurgical resection of
      extensive spinal tumors. This technique allows a very comfortable approach to the
      dura and intradural content, as well as a perfect replacement of the posterior
      spinal arch with supporting elements and an optimal reconstruction of the spinal
      anatomy. A nonexpansive whole lumbar one-piece laminoplasty was performed for
      resection of extensive multilevel lumbar tumors. The authors report an
      illustrative case of a patient who initially presented with a three-year history
      of numbness on both legs and progressive difficulty in walking. Two months before
      admission, he complained of bilateral sciatica and rectourinary dysfunction. A
      spinal magnetic resonance imaging (MRI) documented an intradural tumor extending
      from L2 to S1. The patient underwent a nonexpansive whole lumbar one-piece
      laminoplasty and microsurgical removal of the intradural lesion. The
      postoperative course was uneventful, the sensory disturbances and bilateral
      sciatica early recovered while rectourinary disturbance gradually improved up to
      a complete resolution at one year follow-up. The authors believe that multilevel
      laminoplasty rather than laminectomy is the technique of choice as a posterior
      procedure for extensive lumbar spinal tumors. With this technique, it is possible
      to obtain a very confortable approach to the dura and intradural content, as well
      as a perfect replacement of the posterior spinal arch with supporting elements
      and an optimal reconstruction of the normal spine. Moreover, this method prevents
      postoperative instability and deformity and avoids the so called post-laminectomy
      epidural membrane.

PMID- 18636052
TI  - Endoscopic sinus surgery for a tension pneumocephalus after severe cranio-facial
      trauma.
AB  - Tension pneumocephalus is a rare form of pneumocephalus in which the air is under
      pressure; it is generally due to communication between the atmosphere and the
      intracranial cavity, and is an infrequent (0.88%) complication of cranial trauma.
      Tension pneumocephalus causes an increase in intracranial pressure with
      deterioration of the neurological situation and requires emergency treatment.
      Endoscopic surgery of the paranasal sinuses, which is generally applied in the
      diagnosis and treatment of fistulas with cerebrospinal fluid leakage, was here
      used to treat a case of pneumocephalus due to cranio-ethmoidal communication, in
      a patient we had treated previously for severe cranio-facial trauma.

PMID- 18636053
TI  - Multiple disc herniations in a type II diabetic patient: case report and review
      of the literature.
AB  - Disc herniation is a common pathology associated with physical trauma or
      degenerative diseases. The authors present the case of a patient with 8 disc
      herniations without known risk factors or other associated pathologies except for
      a long story of type II diabetes. Basing on studies reported in literature, it
      can be assumed that diabetes may be the reason of multiple disc herniations in
      this case.

PMID- 18636054
TI  - Concomitant localization of a myxopapillary ependymoma at the middle thoracic
      part of the spinal cord and at the distal part of the filum terminale. Case
      report.
AB  - Myxopapillary ependymomas represent the most frequent type of ependymomas found
      at the conus medullaris-cauda equina-terminal filum level. In this article the
      authors describe the clinical presentation, radiographic findings, operative
      details, and pathological features of a patient with a concomitant presentations
      of a thoracic spinal cord myxopapillary ependymoma and a filum terminale
      myxopapillary ependymoma. A 16-year-old man presented to the Neurosurgery
      Department of the S. Maria delle Grazie Hospital (Naples, Italy) with an
      increased weakness of both the legs with great difficulties with walking and with
      bowel and bladder dysfunction. In a few minutes he becomes paraplegic. Magnetic
      resonance (MR) imaging revealed two ependymomas: the first one was localized in
      the middle thoracic part of the spinal cord and, the second one was localized in
      the cauda at sacral level. Two operations were performed for gross total
      resection of the masses. The first operation was performed at thoracic level and
      the second one was performed at the sacral level after two months. The
      examination demonstrated in both cases a myxopapillary ependymoma. The patient
      experienced complete resolution of her preoperative symptoms. This article
      reports an unusual case of a concomitant presentations of a thoracic spinal cord
      myxopapillary ependymoma and a filum terminale myxopapillary ependymoma
      myxopapillary. To the best of the authors' knowledge, this association has not
      yet been reported. This raises the interesting question of a possible associative
      or causative relationship between these pathologies. The authors considered
      dissemination to be the spread of tumor along the neuraxis to a location separate
      from the primary site. They do not believe that the lesion at the cauda level was
      a drop metastase. As the entire spinal cord and the brain were imaged, and as the
      tumor in the thoracic spinal cord area was we well capsulated, a disseminated
      ependymoma was confidently excluded.

PMID- 18636055
TI  - Endoscopic approach to cubital tunnel syndrome.
AB  - The cubital tunnel syndrome is one of the most common entrapment neuropathy of
      the upper limb. The ulnar nerve can be compressed in the oteofibrous tunnel by
      the bone structures, the Osborne's ligament, the fascia of the ulnar flexor
      muscle of the carpus or of the aponeurosis of the deep flexor of the fingers.
      Pressure values in the cubital tunnel >50 mm Hg induce blocking of intraneural
      circulation with electrodiagnostic modifications, clinical signs and histological
      changes including demyelinazion of the nerve proximal to the cubital tunnel.
      Surgery becomes essential in case of failure of conservative and physical
      therapy. Various surgical techniques have been described in the literature for
      the treatment of the ulnar neuropathy at the elbow. In this paper the authors
      report a new endoscopic technique for the treatment of ulnar nerve entrapment at
      the elbow which requires respect of specific electrodiagnostic and clinical
      criteria of inclusion. The restored joint active motion following elbow
      arthroscopy in osteoarthritis can induce or get worse a ulnar nerve neuropathy;
      endoscopy neurolysis is essential to remove perineural adherences and reduces the
      nerve stress. Immediate well-being of the patient, lesser invasiveness and
      minimum vascular complications are clear advantages of the endoscopic approach,
      while the treatment of the pathologies proximal and distal to the Struther's
      arcade is a limit of the technique.

PMID- 18636056
TI  - Metabolic support of the critically ill: 2008 update.
AB  - Nutrition support in critically ill patients is not merely simple nutrition, but
      rather metabolic support. In the last few years, the pharmacological properties
      of nutrients have been specifically addressed in a new field called
      pharmaconutrition. This review will offer a deeper insight into this field,
      focusing on the properties of arginine, glutamine, antioxidants, and omega-3
      fatty acids as well as the level of blood glycemia which should be maintained in
      critically ill patients.

PMID- 18636057
TI  - Management to optimize organ procurement in brain dead donors.
AB  - The demand for donor organs continues to exceed the number of organs available
      for transplantation. Many reasons may account for this discrepancy, such as the
      lack of consent, the absence of an experienced coordinator team able to solve
      logistical problems, the use of strict donor criteria, and suboptimal,
      unstandardized critical care management of potential organ donors. This has
      resulted in efforts to improve the medical care delivered to potential organ
      donors, so as to reduce organ shortages, improve organ procurement, and promote
      graft survival. The physiological changes that follow brain death entail a high
      incidence of complications jeopardizing potentially transplantable organs.
      Adverse events include cardiovascular changes, endocrine and metabolic
      disturbances, and disruption of internal homeostasis. Brain death also
      upregulates the release of pro-inflammatory molecules. Recent findings support
      the hypothesis that a preclinical lung injury characterized by an enhanced
      inflammatory response is present in potential donors and may predispose
      recipients to an adverse clinical prognosis following lung transplantation. In
      clinical practice, hypotension, diabetes insipidus, relative hypothermia, and
      natremia are more common than disseminated intravascular coagulation, cardiac
      arrhythmias, pulmonary oedema, acute lung injury, and metabolic acidosis.
      Strategies for the management of organ donors exist and consist of the
      normalization of donor physiology. Management has been complicated by the recent
      use of ''marginal'' donors and donors of advanced age or with ''extended''
      criteria. Current guidelines suggest that the priority of critical care
      management for potential organ donors should be shifted from a ''cerebral
      protective'' strategy to a multimodal strategy aimed to preserve peripheral organ
      function.

PMID- 18636058
TI  - Advances in sedation for critically ill patients.
AB  - The use of sedation is required for the majority of mechanically ventilated
      patients in order to ensure comfort. For many years, deep sedation was the
      standard of care to avoid unpleasant memories and anxiety and provide comfort.
      Research over the past decade has shown the importance of using different tools
      to assess the level of sedation in order to guide appropriate dosing of sedatives
      and to measure the clinical response to sedation. Given the progress in recent
      trials in this area, the management of sedation in the Intensive Care Unit (ICU)
      can be improved using various approaches that have shown improved outcomes in the
      ICU. The most prominent of these interventions involves linking daily
      interruptions in sedation (i.e. spontaneous awakening trials, SATs) with
      ventilator weaning protocols that incorporate spontaneous breathing trials
      (SBTs). Intensivists should combine the goals of ensuring patient comfort and
      avoiding unpleasant memories with other important goals that can be achieved with
      these new strategies (i.e. SATs plus SBTs or the so-called ''wake up and breathe
      approach''), such as a three day reduction in time spent on the ventilator, a
      four day reduction in ICU and hospital stays and a 14% absolute reduction in
      death at one year. New choices for sedation, such as alpha-2 agonists and ultra
      short narcotics, are also being actively investigated, which may lead to
      complementary improvements in the future management of these critically ill,
      vulnerable patients.

PMID- 18636059
TI  - The educational process and training of pain clinicians.

PMID- 18636060
TI  - Diuretics in acute kidney injury.
AB  - BACKGROUND: In an acute care setting, diuretics are often prescribed to maintain
      or increase urine output in patients presenting with acute kidney injury (AKI).
      The rationale behind giving diuretics is that they may protect the kidney from
      ischemic injury by maintaining a nonoliguric state. There have been many studies
      both supporting and criticizing diuretic use in AKI for improving overall patient
      outcomes. METHODS: A systematic review of the literature was conducted to
      evaluate the role of diuretics including osmotics, loop diuretics, and nesiritide
      in modifying AKI. RESULTS: There was no evidence to suggest that the use of loop
      diuretics in AKI reduces mortality, the need for dialysis, the number of dialysis
      sessions, or length of Intensive Care Unit/hospital stay or that it increases the
      recovery of renal function. There is no benefit for the use of mannitol as an
      osmotic diuretic over hydration in rhabdomyolysis. In contrast, mannitol was
      found to cause more harm and to induce nephropathy. Nesiritide did not improve
      renal function in patients with decompensated heart failure and mild chronic
      renal insufficiency. Nesiritide may be effective in the prevention of AKI when
      applied in lower doses for a prolonged period of time in patients with mild to
      moderate renal insufficiency. CONCLUSIONS: Diuretics have been shown to be
      ineffective in the prevention of AKI or for improving outcomes once AKI occurs.
      At best, diuretics can help decrease symptoms of pulmonary edema secondary to
      volume overload.

PMID- 18636061
TI  - Stroke in critically ill patients.
AB  - Advances in critical care medicine have led to improved survival rates among
      patients admitted to the Intensive Care unit (ICU), but complications experienced
      during admittance in an ICU may influence long-term outcome and the
      neurocognitive state of these patients. Coagulation disorders, glucose
      intolerance, diabetes, pro-inflammatory state and underlying severe pathologies
      are common risk factors for stroke development in ICU patients. Stroke may result
      in very serious consequences like motor function impairment, neglect and aphasia,
      but in some cases, stroke may not result in any clinical sign in acute phase.
      Recently, more attention has been given to this condition called ''silent
      stroke.'' ''Silent stroke'' could be the foundation of the development of
      neurocognitive impairment and vascular dementia. In ICU survivors, approximately
      1/3 of patients or more will develop chronic neurocognitive impairment. With the
      advent of sensitive techniques for brain imaging, silent brain lesions, including
      brain infarct and white matter changes, have been frequently recognized. Until
      now, epidemiological studies in this field evaluating incidence and consequences
      of stroke in ICU setting are lacking, and prospective studies are required to
      evaluate the impact of this condition on the quality of life, neurocognitive
      outcome and mortality of ICU patients. We believe that when stroke occurs in
      critically ill patients, more attention is typically given to the underlying
      pathologies than stroke, and this may influence the long-term outcome. Guidelines
      for the early management of stroke, commonly used in Stroke Units, should be
      followed, even in critically ill patients in an ICU setting.

PMID- 18636062
TI  - Acute intestinal distress syndrome: the importance of intra-abdominal pressure.
AB  - This review article will focus primarily on the recent literature on abdominal
      compartment syndrome (ACS) as well as the definitions and recommendations
      published by the World Society for the Abdominal Compartment Syndrome (WSACS,
      www.wsacs.org). The risk factors for intra-abdominal hypertension (IAH) and the
      definitions regarding increased intra-abdominal pressure (IAP) will be listed,
      followed by a brief but comprehensive overview of the different mechanisms of end
      organ dysfunction associated with IAH. Measurement techniques for IAP will be
      discussed, as well as recommendations for organ function support in patients with
      IAH. Finally, noninvasive medical management options for IAH, surgical treatment
      for ACS and management of the open abdomen will be briefly discussed.

PMID- 18636063
TI  - State-specific prevalence of obesity among adults--United States, 2007.
AB  - Obesity is associated with reduced quality of life, development of serious
      chronic conditions such as heart disease and diabetes, increased medical care
      costs, and premature death. A Healthy People 2010 objective is to reduce to 15%
      the proportion of adults who are obese. In 2005, no state met this target, and
      (based on self-reported height and weight) 23.9% of adults in the United States
      were obese. To update 2005 estimates of the prevalence of obesity in adults, CDC
      analyzed data from the 2007 Behavioral Risk Factor Surveillance System (BRFSS)
      survey. The results of that analysis indicated that 25.6% of respondents overall
      in 2007 were obese; the prevalence of obesity among adults remained above 15% in
      all states and was above 30% in Alabama, Mississippi, and Tennessee. Enhanced
      collaborative efforts among national, state, and community groups are needed to
      establish, evaluate, and sustain effective programs and policies to reduce the
      prevalence of obesity in the United States.

PMID- 18636064
TI  - Balamuthia amebic encephalitis--California, 1999-2007.
AB  - Balamuthia mandrillaris is a free-living ameba that causes encephalitis in humans
      (both immunocompetent and immunocompromised), horses, dogs, sheep, and nonhuman
      primates. The ameba is present in soil and likely is transmitted by inhalation of
      airborne cysts or by direct contamination of a skin lesion. Approximately 150
      cases of balamuthiasis have been reported worldwide since recognition of the
      disease in 1990. Balamuthiasis is difficult to diagnose because 1) the clinical
      symptoms mimic those of several other types of encephalitis, 2) few laboratories
      perform appropriate diagnostic testing, and 3) many physicians are unaware of the
      disease. The lack of recognition and subsequent delay in diagnosis might be a
      factor in its high mortality. Since 1998, the California Encephalitis Project
      (CEP) has been testing encephalitis cases for both common and uncommon agents
      known to cause encephalitis, including Balamuthia. This report describes the 10
      balamuthiasis cases identified by CEP during 1999-2007. The preliminary diagnoses
      in these cases included neurotuberculosis, viral meningoencephalitis,
      neurocysticercosis, and acute disseminated encephalomyelitis. All but one patient
      died. These findings underscore the importance of increasing awareness among
      clinicians, epidemiologists, and public health officials for timely recognition
      and potential treatment of Balamuthia encephalitis.

PMID- 18636065
TI  - Silicosis-related years of potential life lost before age 65 years--United
      States, 1968-2005.
AB  - Occupational exposure to respirable crystalline silica occurs in construction,
      mining, manufacturing, and other industries and can result in silicosis and other
      lung diseases. Classic (chronic) silicosis results from exposure to relatively
      low concentrations of respirable crystalline silica for >/=years. Exposure to
      higher concentrations of silica for 5-10 years can cause accelerated silicosis,
      and symptoms of acute silicosis can sometimes develop within weeks of initial
      exposure to extreme concentrations of silica. Deaths in young adults from acute
      or accelerated silicosis generally reflect more recent and intense exposures.
      Silicosis is incurable, but preventable through effective control and elimination
      of exposure to respirable crystalline silica. To characterize recent trends in
      premature mortality attributed to silicosis in the United States, CDC analyzed
      annual mortality data from 1968-2005, the most recent years for which complete
      data were available. Years of potential life lost before age 65 years (YPLL) and
      mean YPLL were calculated using standard methodology. During 1968-2005, total
      annual YPLL attributed to silicosis (17,130) declined 90.2%, from 1,441 (mean per
      decedent: 7.7 YPLL) to 141 (mean per decedent: 11.8), with an annual average of
      8.6 YPLL per decedent for the period. However, the proportion of YPLL
      attributable to young silicosis decedents increased; an estimated 3,600-7,300 new
      silicosis cases occur annually. Hazard surveillance, workplace-specific
      interventions, and further silicosis prevention and elimination efforts,
      especially among young adults, are needed.

PMID- 18636066
TI  - Salmonella Litchfield outbreak associated with a hotel restaurant--Atlantic City,
      New Jersey, 2007.
AB  - On July 10, 2007, the Pennsylvania Department of Health notified the New Jersey
      Department of Health and Senior Services (NJDHSS) of three culture-confirmed
      cases of Salmonella Litchfield infection with matching pulsed-field gel
      electrophoresis (PFGE) patterns. Data from PulseNet, the national molecular
      subtyping network for foodborne disease surveillance, confirmed 11 cases
      (including the three from Pennsylvania) of this rarely identified Salmonella
      serotype in five states during a 5-week period; seven of the 11 patients had
      reported recent travel history to Atlantic City, New Jersey. This report
      describes the subsequent investigation led by NJDHSS and the Atlantic City Health
      Department (ACHD), which associated the outbreak with a hotel restaurant in
      Atlantic City. In all, 30 confirmed or probable cases of illness with S.
      Litchfield infection were identified among persons from eight states who had
      eaten at the hotel restaurant, including 10 restaurant food handlers.
      Investigators concluded that the outbreak most likely was associated with fruit
      salad, particularly the honeydew melon component, and that contamination likely
      resulted from an ill food handler. This investigation illustrates the potential
      for recurring food contamination by ill and asymptomatic food handlers and
      underscores the utility of PulseNet to link illnesses that might appear
      unrelated.

PMID- 18636067
TI  - Effect of ovariectomy on blood pressure and venous tone in female spontaneously
      hypertensive rats.
AB  - BACKGROUND: Venous capacitance plays an important role in circulatory
      homeostasis. A number of reports have suggested an effect of estrogen on venous
      function. This study tested the hypothesis that ovariectomy would increase venous
      tone in the female spontaneously hypertensive rat (SHR) via autonomic mechanisms.
      METHODS: Five-week-old female SHR were subjected to sham operation (Sham) or
      ovariectomy (OVX). At 10 weeks of age, the rats were instrumented for the
      measurement of arterial and venous pressure. A balloon catheter was advanced into
      the right atrium. Mean circulatory filling pressure (MCFP), an index of venous
      tone, was calculated. Mean arterial pressure (MAP), heart rate (HR), and MCFP
      were recorded from conscious rats. Postsynaptic adrenergic responsiveness was
      assessed by constructing cumulative dose-response curves to norepinephrine (NE).
      RESULTS: MAP was not significantly affected by ovariectomy (Sham 127 +/- 6 mm Hg
      vs. OVX 130 +/- 3 mm Hg). HR also was not different between groups (Sham 409 +/-
      11 bpm vs. OVX 399 +/- 12 bpm). Conversely, MCFP was significantly, but
      moderately, increased in OVX SHR (Sham 5.2 +/- 0.2 mm Hg vs. OVX 5.9 +/- 0.2 mm
      Hg). Ganglionic blockade produced marked decreases in MAP, HR, and MCFP in both
      groups; however, the responses were not different between groups. Infusion of NE
      caused dose-dependent increases in MAP and MCFP. There were no statistically
      significant differences in these responses between Sham and OVX SHR. CONCLUSION:
      Endogenous ovarian hormones effect a small reduction in MCFP. This effect does
      not appear to be mediated by adrenergic mechanisms.

PMID- 18636068
TI  - Development and validation of a clinical score to identify echocardiographic left
      ventricular hypertrophy in patients with cardiovascular disease.
AB  - BACKGROUND: Echocardiographic (echo) left ventricular hypertrophy (LVH) is an
      independent predictor of mortality. Despite this, screening for LVH in patients
      with overt cardiovascular diseases is not universally done. To help target echo
      screening for LVH in patient population, we developed and validated a simple
      clinical score to help identify those likely to have echo LVH. METHODS: We
      performed two studies. The development cohort consisted of 267 patients with
      angina. The validation cohort consisted of 227 patients with peripheral arterial
      disease. RESULTS: The prevalence of echo LVH in both patient cohorts was 50%. Six
      independent predictors of LVH were identified in the development cohort: age >65
      years (1 point), body mass index >30 kg/m2 (1 point), history of hypertension (1
      point), previous myocardial infarction (1 point), clinic blood pressure >130/80
      mm Hg (1 point) and bundle branch block (BBB) on electrocardiogram (4 points).
      Our clinical score was strongly associated with the presence of LVH in the
      validation cohort. It also showed a significant continuous positive relationship
      (P trend <0.001 in males and P trend = 0.006 in females) with increasing
      quartiles of LV mass in both cohorts. In those without BBB, a modified clinical
      score performed equally well. CONCLUSION: We have developed a simple clinical
      score which quantifies the chance that any patient with manifest cardiovascular
      disease has the added risk factor of LVH. This will help target precious echo
      resources toward individuals who are most likely to have this condition. This
      could potentially lead to better risk stratification in this patient population.

PMID- 18636069
TI  - Effects of the antioxidative beta-blocker celiprolol on endothelial progenitor
      cells in hypertensive rats.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) derived from bone marrow migrate
      to areas of endothelial damage and repair them. EPC function is impaired by
      oxidative stress. We examined the effects of an antioxidative beta1-adrenoceptor
      blocker on the number and function of EPCs in hypertensive rats. METHODS:
      Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were fed diets
      loaded with high salt. The SHRs were treated with celiprolol or atenolol for 2
      weeks. Peripheral blood mononuclear cells (MNCs) were separated, subjected to
      flow cytometric analysis to determine the number of circulating EPCs, and
      cultured to quantify EPC colony formation. EPC migration was evaluated in
      migration assay chambers. EPC senescence was evaluated using beta-galactosidase
      assay. Oxidative stress of EPCs was evaluated using thiobarbituric acid-reactive
      substance (TBARS) assay. The expression of nicotinamine adenine dinucleotide
      phosphate (NAD(P)H) oxidase component mRNAs in the renal cortex, aorta, and heart
      were evaluated by real-time PCR. RESULTS: The number, colony formation, and
      migration of EPCs in SHRs were significantly lower than those in WKY rats. TBARS
      scores in EPCs from SHRs were significantly higher than those from WKY rats.
      Celiprolol increased the number of circulating EPCs and stimulated EPC colony
      formation and migration, while decreasing EPC senescence. Celiprolol inhibited
      oxidation in EPCs from SHRs, and decreased the expression of NAD(P)H oxidase
      component mRNAs in the renal cortex, aorta, and heart. CONCLUSION: EPCs are
      impaired in SHRs in response to oxidative stress. Celiprolol decreases oxidative
      stress in hypertension in vivo and improves EPC numbers and function. It appears,
      therefore, that celiprolol may exert beneficial cardiovascular effects through
      its antioxidative properties.

PMID- 18636070
TI  - Dietary fiber intake in early pregnancy and risk of subsequent preeclampsia.
AB  - BACKGROUND: Substantial epidemiological evidence documents diverse health
      benefits, including reduced risks of hypertension, associated with diets high in
      fiber. Few studies, however, have investigated the extent to which dietary fiber
      intake in early pregnancy is associated with reductions in preeclampsia risk. We
      assessed the relationship between maternal dietary fiber intake in early
      pregnancy and risk of preeclampsia. We also evaluated cross-sectional
      associations of maternal early pregnancy plasma lipid and lipoprotein
      concentrations with fiber intake. METHODS: The study population comprised 1,538
      pregnant Washington State residents. A 121-item food frequency questionnaire
      (FFQ) was used to assess maternal dietary intake, 3 months before and during
      early pregnancy; and generalized linear regression procedures were used to derive
      relative risk (RR) and 95% confidence intervals (CIs). RESULTS: Dietary total
      fiber intake was associated with reduced preeclampsia risk. After adjusting for
      confounders, the RR of preeclampsia for women in the highest (> or =21.2 g/day)
      vs. the lowest quartile (<11.9 g/day) was 0.28 (95% CI = 0.11-0.75). We observed
      associations of similar magnitude when the highest vs. the lowest quartiles of
      water-soluble fiber (RR = 0.30; 95% CI = 0.11-0.86) and insoluble fiber (RR =
      0.35; 95% CI = 0.14-0.87) were evaluated. Mean triglyceride concentrations were
      lower (-11.9 mg/dl, P = 0.02) and high-density lipoprotein cholesterol
      concentrations were higher (+2.63 mg/dl, P = 0.09) for women in the highest
      quartile vs. those in the lowest quartile. CONCLUSIONS: These findings of reduced
      preeclampsia risk with higher total fiber intake corroborate an earlier report;
      and expand the literature by providing evidence, which suggests that dietary
      fiber may attenuate pregnancy-associated dyslipidemia, an important clinical
      characteristic of preeclampsia.

PMID- 18636071
TI  - Pseudoreceptor models in drug design: bridging ligand- and receptor-based virtual
      screening.
AB  - Rational drug design is based on explicit or implicit structure-activity
      relationship models. Typically, receptor-based or ligand-based strategies are
      pursued, depending on the information available about known ligands and the
      receptor structure. Pseudoreceptor models combine the advantages of these two
      strategies and represent a unifying concept for both receptor mapping and ligand
      matching. They can provide an entry point for structure-based modelling in drug
      discovery projects that lack a high-resolution structure of the target. Here, we
      review the field of pseudoreceptor modelling techniques along with recent hit and
      lead finding applications, and critically discuss prerequisites, advantages and
      limitations of the various approaches.

PMID- 18636072
TI  - The genetics of vertebrate myogenesis.
AB  - The molecular, genetic and cellular bases for skeletal muscle growth and
      regeneration have been recently documented in a number of vertebrate species.
      These studies highlight the role of transient subcompartments of the early somite
      as a source of distinct waves of myogenic precursors. Individual myogenic
      progenitor populations undergo a complex series of cell rearrangements and
      specification events in different regions of the body, all of which are
      controlled by distinct gene regulatory networks. Collectively, these studies have
      opened a window into the morphogenetic and molecular bases of the different
      phases of vertebrate myogenesis, from embryo to adult.

PMID- 18636073
TI  - Autophagy in CD4+ T-cell immunity and tolerance.
AB  - Autophagy is a homeostatic process that enables eukaryotic cells to deliver
      cytoplasmic constituents for lysosomal degradation, to recycle nutrients and to
      survive during starvation. In addition to these primordial functions, autophagy
      has emerged as a key mechanism in orchestrating innate and adaptive immune
      responses to intracellular pathogens. Autophagy restricts viral infections as
      well as replication of intracellular bacteria and parasites and delivers
      pathogenic determinants for TLR stimulation and for MHC class II presentation to
      the adaptive immune system. Apart from its role in defense against pathogens,
      autophagy-mediated presentation of self-antigens in the steady state could have a
      crucial role in the induction and maintenance of CD4(+) T-cell tolerance. This
      review describes the mechanisms by which the immune system utilizes autophagic
      degradation of cytoplasmic material to regulate adaptive immune responses.

PMID- 18636074
TI  - Cbfa1-dependent expression of an interferon-inducible p204 protein is required
      for chondrocyte differentiation.
AB  - We reported earlier that an interferon-inducible p204 protein serves as a
      cofactor of Cbfa1 and promotes osteogenesis. Here we establish that p204
      demonstrates prominent expression in growth plate chondrocytes. It is
      differentially expressed in the course of bone morphogenetic protein-2-triggered
      chondrocyte differentiation of pluripotent C3H10T1/2 cells. This expression is
      probably due to the activation of p204 gene by Cbfa1 and repression by Sox5
      transcription factor. Cbfa1 and Sox5 bind to the 5'-flanking regulatory region of
      p204 gene at their consensus binding elements. Overexpression of p204 accelerates
      chondrocyte hypertrophy, as revealed by enhanced expression of type X Collagen
      and matrix metalloproteinase-13; however, knockdown of p204 via an siRNA approach
      abolishes hypertrophic chondrocyte differentiation. p204 acts as a cofactor of
      Cbfa1 in chondrocyte hypertrophy: (1) overexpression of p204 augments, whereas
      suppression of p204 decreases, the Cbfa1-dependent transactivation of a Collagen
      X-specific reporter gene; (2) p204 enhances Cbfa1-mediated chondrocyte
      hypertrophy; and (3) p204 associates with Cbfa1 in chondrocyte differentiation.
      In addition, altered expression of p204 in chondrocyte hypertrophy was
      accompanied by altered levels of Indian hedgehog (IHH) and parathyroid
      hormone/parathyroid hormone-related peptide receptor-1 (PTHR1). Collectively,
      p204 is a novel regulator of chondrocyte differentiation by (1) acting as a
      coactivator of Cbfa1 and (2) affecting IHH/PTPrP signaling.

PMID- 18636075
TI  - Cleavage of phospholipase D1 by caspase promotes apoptosis via modulation of the
      p53-dependent cell death pathway.
AB  - The enzymatic activity of phospholipase D (PLD) is known to be essential for cell
      survival and protection from apoptosis. However, the mechanisms regulating PLD
      activity during apoptosis remain unknown. Here we report that cleavage of PLD1 by
      caspases facilitates p53-mediated apoptosis. Cleavage of PLD1 into an N-terminal
      fragment (NF-PLD1) and a C-terminal fragment at the amino-acid sequence,
      DDVD(545), led to a reduction in PLD1 activity. However, a caspase-resistant
      mutant form of PLD1 retained significant levels of enzymatic activity and
      apoptotic function as compared to wild-type PLD1. Exogenous NF-PLD1 expression
      induced apoptosis through a dominant-negative effect on the activity of
      endogenous PLD1. During apoptosis, a small fraction of PLD1 is cleaved by
      caspases in a p53-independent manner and NF-PLD1 amplifies apoptotic signaling
      through inhibition of the remaining PLD1 activity. As PLD1 suppresses the ATM
      Chk2-p53 pathway, elimination of PLD1 activity through NF-PLD1 or si-RNA against
      PLD1 increases apoptosis in a p53-dependent manner. Taken together, our results
      reveal that cleavage of PLD1 by caspases promotes apoptosis via modulation of the
      p53-dependent cell death pathway.

PMID- 18636076
TI  - Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of
      polyglutamine-expanded huntingtin and related proteinopathies.
AB  - The formation of intra-neuronal mutant protein aggregates is a characteristic of
      several human neurodegenerative disorders, like Alzheimer's disease, Parkinson's
      disease (PD) and polyglutamine disorders, including Huntington's disease (HD).
      Autophagy is a major clearance pathway for the removal of mutant huntingtin
      associated with HD, and many other disease-causing, cytoplasmic, aggregate-prone
      proteins. Autophagy is negatively regulated by the mammalian target of rapamycin
      (mTOR) and can be induced in all mammalian cell types by the mTOR inhibitor
      rapamycin. It can also be induced by a recently described cyclical mTOR
      independent pathway, which has multiple drug targets, involving links between
      Ca(2+)-calpain-G(salpha) and cAMP-Epac-PLC-epsilon-IP(3) signalling. Both
      pathways enhance the clearance of mutant huntingtin fragments and attenuate
      polyglutamine toxicity in cell and animal models. The protective effects of
      rapamycin in vivo are autophagy-dependent. In Drosophila models of various
      diseases, the benefits of rapamycin are lost when the expression of different
      autophagy genes is reduced, implicating that its effects are not mediated by
      autophagy-independent processes (like mild translation suppression). Also, the
      mTOR-independent autophagy enhancers have no effects on mutant protein clearance
      in autophagy-deficient cells. In this review, we describe various drugs and
      pathways inducing autophagy, which may be potential therapeutic approaches for HD
      and related conditions.

PMID- 18636077
TI  - The intestinal epithelium compensates for p53-mediated cell death and guarantees
      organismal survival.
AB  - Mdm2 is the major inhibitor of the p53 tumor suppressor. Loss of Mdm2 in mice or
      in specific tissues of the mouse always yields p53-dependent lethal phenotypes.
      However, the role of Mdm2 in tissues with high turnover capacity is unknown. We
      have engineered mice lacking Mdm2 in the intestinal epithelium using the Cre/LoxP
      system. Loss of Mdm2 (Mdm2(intDelta)) results in viable animals, but neonates
      display multiple intestinal abnormalities such as hyperplasia, enterocyte
      vacuolization, and inflammation. These defects correlate with a drastic increase
      in p53-dependent apoptosis in highly proliferative and differentiated cells.
      Unexpectedly, the observed phenotypes disappear with age. The tissue selects
      against Mdm2-null cells and increases its proliferative capacity. Additionally,
      the intestinal stem and progenitor cell populations are enriched leading to an
      increase in crypt fission events. Enhanced proliferation is achieved by
      activation of the canonical Wnt and EGFR-mediated Ras/MAPK pathways. While Mdm2
      is a critical inhibitor of p53 in the intestinal epithelium, the tissue employs a
      series of processes that compensate for cell death.

PMID- 18636078
TI  - C/EBPbeta represses p53 to promote cell survival downstream of DNA damage
      independent of oncogenic Ras and p19(Arf).
AB  - CCAAT/enhancer-binding protein-beta (C/EBPbeta) is a mediator of cell survival
      and tumorigenesis. When C/EBPbeta(-/-) mice are treated with carcinogens that
      produce oncogenic Ras mutations in keratinocytes, they respond with abnormally
      elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this
      aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53,
      it is not known whether upregulated p53 results from oncogenic Ras and its
      ability to induce p19(Arf) and/or activate DNA-damage response pathways or from
      direct carcinogen-induced DNA damage. We report that p19(Arf) is dramatically
      elevated in C/EBPbeta(-/-) epidermis and that C/EBPbeta represses a p19(Arf)
      promoter reporter. To determine whether p19(Arf) is responsible for the
      proapoptotic phenotype in C/EBPbeta(-/-) mice, C/EBPbeta(-/-);p19(Arf-/-) mice
      were generated. C/EBPbeta(-/-);p19(Arf-/-) mice responded to carcinogen treatment
      with increased p53 and apoptosis, indicating p19(Arf) is not essential. To
      ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in
      C/EBPbeta(-/-) epidermis, we generated K14-ER:Ras;C/EBPbeta(-/-) mice. Oncogenic
      Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or
      apoptosis. Finally, when C/EBPbeta(-/-) mice were treated with differing types of
      DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed
      aberrant levels of p53 and apoptosis. These results indicate that C/EBPbeta
      represses p53 to promote cell survival downstream of DNA damage and suggest that
      inhibition of C/EBPbeta may be a target for cancer cotherapy to increase the
      efficacy of alkylating chemotherapeutic agents.

PMID- 18636079
TI  - Bilateral hypopyon and vitritis associated with rifabutin therapy in an
      immunocompetent patient taking itraconazole.

PMID- 18636080
TI  - Retinal folds and retinoschisis in accidental and non-accidental head injury.
AB  - AIMS: To report the similarity of retinal findings in an infant who sustained an
      accidental head injury and an infant with non-accidental head trauma. METHODS:
      Two male infants sustained head injuries with skull fractures. Case 1 was an
      accidental head injury and case 2 was a non-accidental head injury. RESULTS: On
      examination, in case 1, there were four superficial retinal haemorrhages in the
      right fundus. The left eye had a haemorrhagic optic disc oedema with extensive
      retinal haemorrhages, retinal folds, and schitic cavities within the retina at
      the posterior pole. In case 2, the right fundus had a single blot haemorrhage at
      the posterior pole. The left fundus revealed optic disc haemorrhage and oedema
      with extensive retinal haemorrhages. There was a haemorrhagic retinoschisis with
      a retinal fold. CONCLUSIONS: The two cases, one with accidental and the other
      with non-accidental injury, demonstrate very similar ophthalmic findings. This
      supports the argument that there may be no retinal signs seen exclusively in non
      accidental head injury.

PMID- 18636081
TI  - Modelling lifetime cost consequences of ReSTOR for presbyopia in four European
      countries.
AB  - AIMS: To compare the lifetime cost consequences, in France, Italy, Germany and
      Spain, of liberating presbyopic patients from spectacles by implanting the
      multifocal intraocular lens ReSTOR. METHODS: A Markov model was created to
      compare a patient cohort implanted with ReSTOR at age 45 years, with a cohort
      using spectacles, until death or age 100 years. Prevalence rates of patients not
      requiring spectacles after surgery were obtained from clinical trials. Resource
      utilisation included implant surgery, spectacles, visits to ophthalmologists and
      optic centres, transport and time lost by patients. Economic perspectives were
      those of society and sickness funds. Mortality rates were introduced into the
      model. Cataract surgery was allowed just for the spectacles-only cohort. RESULTS:
      Rate of spectacle independence was fixed at 80% for ReSTOR. When time spent to
      care for refraction was not taken into account, lifelong ReSTOR cost was higher
      than spectacles in all countries (293 euro; 1013 euro), according to the societal
      perspective. When time was included, cost saving was observed in Italy (136 euro)
      and the incremental cost to be free of spectacles comprised between ?[euro]11 and
      ?[euro]816. According to the NHS perspective, ReSTOR is a cost saving strategy (
      274 euro; -605 euro). CONCLUSIONS: At a 3% discount rate, savings achieved by
      liberating patients from spectacles counterbalanced partially the initially
      higher cost of ReSTOR according to the society perspective. ReSTOR could be
      considered as cost-effective in the four countries provided that the willingness
      to pay of patients to be free of spectacles would be lower than 23.65 euro/year.

PMID- 18636082
TI  - Pupil abnormalities in 131 cases of genetically defined inherited peripheral
      neuropathy.
AB  - AIM: To investigate and correlate the frequency and types of pupil abnormalities
      that are associated with hereditary peripheral neuropathy in a large cohort of
      patients prospectively examined. METHODS: A prospective study between 1998 and
      2007. Patients were enrolled and examined after being seen in the neurology
      clinic. Data were collected on demographics, family and medical history. Patients
      had eye and pupillography testing carried out as well as being neurologically and
      genetically investigated. RESULTS: A consecutive series of 131 cases of inherited
      peripheral neuropathy were seen and categorized into five groups: familial
      amyloid polyneuropathy (FAP), Charcot Marie Tooth disease (CMT), hereditary
      neuropathywith liability to pressure palsies (HNPP), Refsum's disease, and
      hereditary sensory and autonomic neuropathy. A number of unreported mutations
      were identified in these patient groups. Pupil abnormalities were common in the
      Refsum's group, with frequent abnormally small pupils. The inherited neuropathies
      commonly associated with autonomic abnormalities were frequently found to have
      developed bilateral Horner's syndrome, which was particularly prevalent in our
      FAP series. Abnormalities were rare in HNPP and CMT type 1, but CMT type 2 showed
      frequent and varied pupil defects. The results describe the pupil abnormalities
      that were frequently associated with the particular group of inherited neuropathy
      patients, but we could not predict the genetic defect or the neuropathy severity.
      CONCLUSIONS: This is the first study of the pupil abnormalities found in the
      inherited neuropathies and provides an overview of the frequency and type of
      defects seen in a large number of cases. This series along with the detailed
      tables will act as an important diagnostic aid in assessing these patients.

PMID- 18636083
TI  - Pegaptanib sodium for occult choroidal neovascularization in neovascular age
      related macular degeneration: a prospective case series.
AB  - PURPOSE: To assess the effects of pegaptanib in the treatment of subfoveal occult
      choroidal neovascularisation (CNV) associated with neovascular age-related
      macular degeneration (NV-AMD) in a compassionate use program in France. METHODS:
      Pegaptanib was authorized for patients with CNV-associated visual impairment and
      in whom usual care (thermal laser photocoagulation or photodynamic therapy with
      verteporfin) was not appropriate. Patients with occult CNV lesions received
      intravitreous pegaptanib (0.3 mg every 6 weeks) and were followed with repeated
      fluorescein angiography, scanning laser ophthalmoscopy-infracyanine green
      angiography, and ocular coherence tomography through 52 weeks. RESULTS: Of 56
      patients (predominantly occult, N=22; purely occult, N=8; occult with
      chorioretinal anastomosis, N=12; occult with pigment epithelial detachment,
      N=14), 30% had earlier treatment. All received eight pegaptanib injections. At
      week 52, 79% were responders (lost <15 letters of visual acuity), 43% gained
      >or=0 letters, and 9% gained >or=15 letters. The best functional results were
      obtained in the predominantly and pure occult subgroups (responders, 86 and 75%;
      gained >or=0 letters, 50 and 50%). Maximum visual outcomes that correlated with
      morphologic improvements on each diagnostic imaging tool were seen after at least
      three injections. No significant ocular or systemic adverse events occurred.
      CONCLUSION: Treatment with pegaptanib was associated with objective functional
      improvements that can be correlated with objective clinical improvements on
      routine diagnostic imaging tools in patients with occult NV-AMD. Optimum
      treatment results appear after at least 4 months of therapy in the majority of
      cases.

PMID- 18636084
TI  - 'Finitics'. A plea for biological realism.

PMID- 18636085
TI  - When flies and mice develop cancer. Meeting on development and cancer.

PMID- 18636087
TI  - A ferry between cultures. Crafting a new profession at the intersection of
      science and society.

PMID- 18636086
TI  - The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral
      response.
AB  - On detecting viral RNAs, the RNA helicase retinoic acid-inducible gene I (RIG-I)
      activates the interferon regulatory factor 3 (IRF3) signalling pathway to induce
      type I interferon (IFN) gene transcription. How this antiviral signalling pathway
      might be negatively regulated is poorly understood. Microarray and bioinformatic
      analysis indicated that the expression of RIG-I and that of the tumour suppressor
      CYLD (cylindromatosis), a deubiquitinating enzyme that removes Lys 63-linked
      polyubiquitin chains, are closely correlated, suggesting a functional association
      between the two molecules. Ectopic expression of CYLD inhibits the IRF3
      signalling pathway and IFN production triggered by RIG-I; conversely, CYLD
      knockdown enhances the response. CYLD removes polyubiquitin chains from RIG-I as
      well as from TANK binding kinase 1 (TBK1), the kinase that phosphorylates IRF3,
      coincident with an inhibition of the IRF3 signalling pathway. Furthermore, CYLD
      protein level is reduced in the presence of tumour necrosis factor and viral
      infection, concomitant with enhanced IFN production. These findings show that
      CYLD is a negative regulator of RIG-I-mediated innate antiviral response.

PMID- 18636088
TI  - Virus meets RNAi. Symposium on antiviral applications of RNA interference.

PMID- 18636089
TI  - The juxtaposition of a promoter with a locus control region transcriptional
      domain activates gene expression.
AB  - Nonlinear chromatin configurations can juxtapose widely separated elements within
      a genomic locus; however, it remains unclear how these structures are established
      and contribute to transcriptional control. A 5'-remote locus control region (LCR)
      regulates the human growth hormone (hGH-N) gene. HSI, a pituitary-specific
      component of the hGH LCR, establishes a domain of polymerase II (PolII)
      transcription 5' to hGH-N. Repression of this transcriptional domain by HSI
      deletion or PolII blockade decreases hGH-N expression. Here, we show that hGH-N
      activation is accompanied by positioning of the hGH-N promoter to this LCR
      transcriptional domain. Selectively blocking LCR transcription inhibits the
      formation of this active 'looped' conformation. Thus, HSI is crucial for
      establishing a domain of noncoding PolII transcription, and this domain is
      intimately linked with chromatin organization of the active hGH-N locus. This
      integration of LCR transcription with chromatin reconfiguration constitutes a
      robust pathway for long-range gene activation.

PMID- 18636090
TI  - Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon
      mediated IRF activation.
AB  - Viruses are detected by different classes of pattern recognition receptors
      (PRRs), such as Toll-like receptors and RIG-like helicases. Engagement of PRRs
      leads to activation of interferon (IFN)-regulatory factor 3 (IRF3) and IRF7
      through IKKepsilon and TBK1 and consequently IFN-beta induction. Vaccinia virus
      (VACV) encodes proteins that manipulate host signalling, sometimes by targeting
      uncharacterised proteins. Here, we describe a novel VACV protein, K7, which can
      inhibit PRR-induced IFN-beta induction by preventing TBK1/IKKepsilon-mediated IRF
      activation. We identified DEAD box protein 3 (DDX3) as a host target of K7.
      Expression of DDX3 enhanced Ifnb promoter induction by TBK1/IKKepsilon, whereas
      knockdown of DDX3 inhibited this, and virus- or dsRNA-induced IRF3 activation.
      Further, dominant-negative DDX3 inhibited virus-, dsRNA- and cytosolic DNA
      stimulated Ccl5 promoter induction, which is also TBK1/IKKepsilon dependent. Both
      K7 binding and enhancement of Ifnb induction mapped to the N-terminus of DDX3.
      Furthermore, virus infection induced an association between DDX3 and IKKepsilon.
      Therefore, this study shows for the first time the involvement of a DEAD box
      helicase in TBK1/IKKepsilon-mediated IRF activation and Ifnb promoter induction.

PMID- 18636091
TI  - Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors.
AB  - NR3 subtype glutamate receptors have a unique developmental expression profile,
      but are the least well-characterized members of the NMDA receptor gene family,
      which have key roles in synaptic plasticity and brain development. Using ligand
      binding assays, crystallographic analysis, and all atom MD simulations, we
      investigate mechanisms underlying the binding by NR3A and NR3B of glycine and D
      serine, which are candidate neurotransmitters for NMDA receptors containing NR3
      subunits. The ligand binding domains of both NR3 subunits adopt a similar extent
      of domain closure as found in the corresponding NR1 complexes, but have a unique
      loop 1 structure distinct from that in all other glutamate receptor ion channels.
      Within their ligand binding pockets, NR3A and NR3B have strikingly different
      hydrogen bonding networks and solvent structures from those found in NR1, and
      fail to undergo a conformational rearrangement observed in NR1 upon binding the
      partial agonist ACPC. MD simulations revealed numerous interdomain contacts,
      which stabilize the agonist-bound closed-cleft conformation, and a novel twisting
      motion for the loop 1 helix that is unique in NR3 subunits.

PMID- 18636092
TI  - Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory
      connexin43-binding sites.
AB  - PDZ domain scaffold proteins are capable of assembling macromolecular protein
      complexes in diverse cellular processes through PDZ-mediated binding to a short
      peptide fragment at the carboxyl tail of target proteins. How each PDZ domain
      specifically recognizes its target protein(s) remains a major conceptual
      question, as at least a few out of the several hundred PDZ domains in each
      eukaryotic genome share overlapping binding properties with any given target
      protein. Here, we show that the domain-swapped dimerization of zonula occludens-1
      PDZ2 generates a distinct interface that functions together with the well
      separated canonical carboxyl tail-binding pocket in each PDZ unit in binding to
      connexin43 (Cx43). We further demonstrate that the charge-charge interaction
      network formed by residues in the PDZ dimer interface and upstream residues of
      the Cx43 peptide not only provides the unprecedented interaction specificity for
      the complex but may also function as a phosphorylation-mediated regulatory switch
      for the dynamics of the Cx43 gap junctions. Finally, we provide evidence that
      such domain-swapped dimer assembly also occurs in other PDZ domain scaffold
      proteins. Therefore, our findings present a new paradigm for understanding how
      some PDZ domain proteins specifically bind to and regulate the functions of their
      target proteins.

PMID- 18636093
TI  - Crystal structures of the OmpF porin: function in a colicin translocon.
AB  - The OmpF porin in the Escherichia coli outer membrane (OM) is required for the
      cytotoxic action of group A colicins, which are proposed to insert their
      translocation and active domains through OmpF pores. A crystal structure was
      sought of OmpF with an inserted colicin segment. A 1.6 A OmpF structure, obtained
      from crystals formed in 1 M Mg2+, has one Mg2+ bound in the selectivity filter
      between Asp113 and Glu117 of loop 3. Co-crystallization of OmpF with the unfolded
      83 residue glycine-rich N-terminal segment of colicin E3 (T83) that occludes OmpF
      ion channels yielded a 3.0 A structure with inserted T83, which was obtained
      without Mg2+ as was T83 binding to OmpF. The incremental electron density could
      be modelled as an extended poly-glycine peptide of at least seven residues. It
      overlapped the Mg2+ binding site obtained without T83, explaining the absence of
      peptide binding in the presence of Mg2+. Involvement of OmpF in colicin passage
      through the OM was further documented by immuno-extraction of an OM complex, the
      colicin translocon, consisting of colicin E3, BtuB and OmpF.

PMID- 18636094
TI  - Extracellular Alix regulates integrin-mediated cell adhesions and extracellular
      matrix assembly.
AB  - Alix (ALG-2-interacting protein X), a cytoplasmic adaptor protein involved in
      endosomal sorting and actin cytoskeleton assembly, is required for the
      maintenance of fibroblast morphology. As Alix has sequence similarity to adhesin
      in Entamoeba histolytica, and we observed that Alix is secreted, we determined
      whether extracellular Alix affects fibroblast morphology. Here, we demonstrate
      that secreted Alix is deposited on the substratum of non-immortalized WI38
      fibroblasts. Antibody binding to extracellular Alix retards WI38 cell adhesion
      and spreading on fibronectin and vitronectin. Alix knockdown in WI38 cells
      reduces spreading and fibronectin assembly, and the effect is partially
      complemented by coating recombinant Alix on the cell substratum. Immortalized
      NIH/3T3 fibroblasts deposit less Alix on the substratum and have defects in
      alpha5beta1-integrin functions. Coating recombinant Alix on the culture
      substratum for NIH/3T3 cells promotes alpha5beta1-integrin-mediated cell
      adhesions and fibronectin assembly, and these effects require the aa 605-709
      region of Alix. These findings demonstrate that a sub-population of Alix
      localizes extracellularly and regulates integrin-mediated cell adhesions and
      fibronectin matrix assembly.

PMID- 18636095
TI  - Regulation of contractile vacuole formation and activity in Dictyostelium.
AB  - The contractile vacuole (CV) system is the osmoregulatory organelle required for
      survival for many free-living cells under hypotonic conditions. We identified a
      new CV regulator, Disgorgin, a TBC-domain-containing protein, which translocates
      to the CV membrane at the late stage of CV charging and regulates CV-plasma
      membrane fusion and discharging. disgorgin(-) cells produce large CVs due to
      impaired CV-plasma membrane fusion. Disgorgin is a specific GAP for Rab8A-GTP,
      which also localizes to the CV and whose hydrolysis is required for discharging.
      We demonstrate that Drainin, a previously identified TBC-domain-containing
      protein, lies upstream from Disgorgin in this pathway. Unlike Disgorgin, Drainin
      lacks GAP activity but functions as a Rab11A effector. The BEACH family proteins
      LvsA and LvsD were identified in a suppressor/enhancer screen of the disgorgin(-)
      large CV phenotype and demonstrated to have distinct functions in regulating CV
      formation. Our studies help define the pathways controlling CV function.

PMID- 18636096
TI  - Dynamics of immune escape during HIV/SIV infection.
AB  - Several studies have shown that cytotoxic T lymphocytes (CTLs) play an important
      role in controlling HIV/SIV infection. Notably, the observation of escape mutants
      suggests a selective pressure induced by the CTL response. However, it remains
      difficult to assess the definite role of the cellular immune response. We devise
      a computational model of HIV/SIV infection having a broad cellular immune
      response targeting different viral epitopes. The CTL clones are stimulated by
      viral antigen and interact with the virus population through cytotoxic killing of
      infected cells. Consequently, the virus population reacts through the acquisition
      of CTL escape mutations. Our model provides realistic virus dynamics and
      describes several experimental observations. We postulate that inter-clonal
      competition and immunodominance may be critical factors determining the
      sequential emergence of escapes. We show that even though the total killing
      induced by the CTL response can be high, escape rates against a single CTL clone
      are often slow and difficult to estimate from infrequent sequence measurements.
      Finally, our simulations show that a higher degree of immunodominance leads to
      more frequent escape with a reduced control of viral replication but a
      substantially impaired replicative capacity of the virus. This result suggests
      two strategies for vaccine design: Vaccines inducing a broad CTL response should
      decrease the viral load, whereas vaccines stimulating a narrow but dominant CTL
      response are likely to induce escape but may dramatically reduce the replicative
      capacity of the virus.

PMID- 18636097
TI  - The ascent of the abundant: how mutational networks constrain evolution.
AB  - Evolution by natural selection is fundamentally shaped by the fitness landscapes
      in which it occurs. Yet fitness landscapes are vast and complex, and thus we know
      relatively little about the long-range constraints they impose on evolutionary
      dynamics. Here, we exhaustively survey the structural landscapes of RNA molecules
      of lengths 12 to 18 nucleotides, and develop a network model to describe the
      relationship between sequence and structure. We find that phenotype abundance-
      the number of genotypes producing a particular phenotype--varies in a predictable
      manner and critically influences evolutionary dynamics. A study of naturally
      occurring functional RNA molecules using a new structural statistic suggests that
      these molecules are biased toward abundant phenotypes. This supports an "ascent
      of the abundant" hypothesis, in which evolution yields abundant phenotypes even
      when they are not the most fit.

PMID- 18636098
TI  - Emergent synchronous bursting of oxytocin neuronal network.
AB  - When young suckle, they are rewarded intermittently with a let-down of milk that
      results from reflex secretion of the hormone oxytocin; without oxytocin, newly
      born young will die unless they are fostered. Oxytocin is made by magnocellular
      hypothalamic neurons, and is secreted from their nerve endings in the pituitary
      in response to action potentials (spikes) that are generated in the cell bodies
      and which are propagated down their axons to the nerve endings. Normally,
      oxytocin cells discharge asynchronously at 1-3 spikes/s, but during suckling,
      every 5 min or so, each discharges a brief, intense burst of spikes that release
      a pulse of oxytocin into the circulation. This reflex was the first, and is
      perhaps the best, example of a physiological role for peptide-mediated
      communication within the brain: it is coordinated by the release of oxytocin from
      the dendrites of oxytocin cells; it can be facilitated by injection of tiny
      amounts of oxytocin into the hypothalamus, and it can be blocked by injection of
      tiny amounts of oxytocin antagonist. Here we show how synchronized bursting can
      arise in a neuronal network model that incorporates basic observations of the
      physiology of oxytocin cells. In our model, bursting is an emergent behaviour of
      a complex system, involving both positive and negative feedbacks, between many
      sparsely connected cells. The oxytocin cells are regulated by independent
      afferent inputs, but they interact by local release of oxytocin and
      endocannabinoids. Oxytocin released from the dendrites of these cells has a
      positive-feedback effect, while endocannabinoids have an inhibitory effect by
      suppressing the afferent input to the cells.

PMID- 18636099
TI  - Memory switches in chemical reaction space.
AB  - Just as complex electronic circuits are built from simple Boolean gates, diverse
      biological functions, including signal transduction, differentiation, and stress
      response, frequently use biochemical switches as a functional module. A
      relatively small number of such switches have been described in the literature,
      and these exhibit considerable diversity in chemical topology. We asked if
      biochemical switches are indeed rare and if there are common chemical motifs and
      family relationships among such switches. We performed a systematic exploration
      of chemical reaction space by generating all possible stoichiometrically valid
      chemical configurations up to 3 molecules and 6 reactions and up to 4 molecules
      and 3 reactions. We used Monte Carlo sampling of parameter space for each such
      configuration to generate specific models and checked each model for switching
      properties. We found nearly 4,500 reaction topologies, or about 10% of our tested
      configurations, that demonstrate switching behavior. Commonly accepted
      topological features such as feedback were poor predictors of bistability, and we
      identified new reaction motifs that were likely to be found in switches.
      Furthermore, the discovered switches were related in that most of the larger
      configurations were derived from smaller ones by addition of one or more
      reactions. To explore even larger configurations, we developed two tools: the
      "bistabilizer," which converts almost-bistable systems into bistable ones, and
      frequent motif mining, which helps rank untested configurations. Both of these
      tools increased the coverage of our library of bistable systems. Thus, our
      systematic exploration of chemical reaction space has produced a valuable
      resource for investigating the key signaling motif of bistability.

PMID- 18636100
TI  - Intrinsic gain modulation and adaptive neural coding.
AB  - In many cases, the computation of a neural system can be reduced to a receptive
      field, or a set of linear filters, and a thresholding function, or gain curve,
      which determines the firing probability; this is known as a linear/nonlinear
      model. In some forms of sensory adaptation, these linear filters and gain curve
      adjust very rapidly to changes in the variance of a randomly varying driving
      input. An apparently similar but previously unrelated issue is the observation of
      gain control by background noise in cortical neurons: the slope of the firing
      rate versus current (f-I) curve changes with the variance of background random
      input. Here, we show a direct correspondence between these two observations by
      relating variance-dependent changes in the gain of f-I curves to characteristics
      of the changing empirical linear/nonlinear model obtained by sampling. In the
      case that the underlying system is fixed, we derive relationships relating the
      change of the gain with respect to both mean and variance with the receptive
      fields derived from reverse correlation on a white noise stimulus. Using two
      conductance-based model neurons that display distinct gain modulation properties
      through a simple change in parameters, we show that coding properties of both
      these models quantitatively satisfy the predicted relationships. Our results
      describe how both variance-dependent gain modulation and adaptive neural
      computation result from intrinsic nonlinearity.

PMID- 18636101
TI  - Genome-wide expression patterns and the genetic architecture of a fundamental
      social trait.
AB  - Explaining how interactions between genes and the environment influence social
      behavior is a fundamental research goal, yet there is limited relevant
      information for species exhibiting natural variation in social organization. The
      fire ant Solenopsis invicta is characterized by a remarkable form of social
      polymorphism, with the presence of one or several queens per colony and the
      expression of other phenotypic and behavioral differences being completely
      associated with allelic variation at a single Mendelian factor marked by the gene
      Gp-9. Microarray analyses of adult workers revealed that differences in the Gp-9
      genotype are associated with the differential expression of an unexpectedly small
      number of genes, many of which have predicted functions, implying a role in
      chemical communication relevant to the regulation of colony queen number. Even
      more surprisingly, worker gene expression profiles are more strongly influenced
      by indirect effects associated with the Gp-9 genotypic composition within their
      colony than by the direct effect of their own Gp-9 genotype. This constitutes an
      unusual example of an "extended phenotype" and suggests a complex genetic
      architecture with a single Mendelian factor, directly and indirectly influencing
      the individual behaviors that, in aggregate, produce an emergent colony-level
      phenotype.

PMID- 18636102
TI  - NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
AB  - Immunity to the murine cytomegalovirus (MCMV) is critically dependent on the
      innate response for initial containment of viral replication, resolution of
      active infection, and proper induction of the adaptive phase of the anti-viral
      response. In contrast to NK cells, the Valpha14 invariant natural killer T cell
      response to MCMV has not been examined. We found that Valpha14i NK T cells become
      activated and produce significant levels of IFN-gamma, but do not proliferate or
      produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb
      and adoptive transfer of Valpha14i NK T cells into MCMV-infected CD1d(-/-) mice
      demonstrate that CD1d is dispensable for Valpha14i NK T cell activation. In
      contrast, both IFN-alpha/beta and IL-12 are required for optimal activation.
      Valpha14i NK T cell-derived IFN-gamma is partially dependent on IFN-alpha/beta
      but highly dependent on IL-12. Valpha14i NK T cells contribute to the immune
      response to MCMV and amplify NK cell-derived IFN-gamma. Importantly, mortality is
      increased in CD1d(-/-) mice in response to high dose MCMV infection when compared
      to heterozygote littermate controls. Collectively, these findings illustrate the
      plasticity of Valpha14i NK T cells that act as effector T cells during bacterial
      infection, but have NK cell-like behavior during the innate immune response to
      MCMV infection.

PMID- 18636103
TI  - MDA-5 recognition of a murine norovirus.
AB  - Noroviruses are important human pathogens responsible for most cases of viral
      epidemic gastroenteritis worldwide. Murine norovirus-1 (MNV-1) is one of several
      murine noroviruses isolated from research mouse facilities and has been used as a
      model of human norovirus infection. MNV-1 infection has been shown to require
      components of innate and adaptive immunity for clearance; however, the initial
      host protein that recognizes MNV-1 infection is unknown. Because noroviruses are
      RNA viruses, we investigated whether MDA5 and TLR3, cellular sensors that
      recognize dsRNA, are important for the host response to MNV-1. We demonstrate
      that MDA5-/- dendritic cells(DC) have a defect in cytokine response to MNV-1. In
      addition, MNV-1 replicates to higher levels in MDA5-/- DCs as well as in MDA5-/-
      mice in vivo. Interestingly, TLR3-/- DCs do not have a defect in vitro, but TLR3
      /- mice have a slight increase in viral titers. This is the first demonstration
      of an innate immune sensor for norovirus and shows that MDA5 is required for the
      control of MNV-1 infection. Knowledge of the host response to MNV-1 may provide
      keys for prevention and treatment of the human disease.

PMID- 18636105
TI  - Computational biology resources lack persistence and usability.

PMID- 18636104
TI  - E1 ubiquitin-activating enzyme UBA-1 plays multiple roles throughout C. elegans
      development.
AB  - Poly-ubiquitination of target proteins typically marks them for destruction via
      the proteasome and provides an essential mechanism for the dynamic control of
      protein levels. The E1 ubiquitin-activating enzyme lies at the apex of the
      ubiquitination cascade, and its activity is necessary for all subsequent steps in
      the reaction. We have isolated a temperature-sensitive mutation in the
      Caenorhabditis elegans uba-1 gene, which encodes the sole E1 enzyme in this
      organism. Manipulation of UBA-1 activity at different developmental stages
      reveals a variety of functions for ubiquitination, including novel roles in sperm
      fertility, control of body size, and sex-specific development. Levels of
      ubiquitin conjugates are substantially reduced in the mutant, consistent with
      reduced E1 activity. The uba-1 mutation causes delays in meiotic progression in
      the early embryo, a process that is known to be regulated by ubiquitin-mediated
      proteolysis. The uba-1 mutation also demonstrates synthetic lethal interactions
      with alleles of the anaphase-promoting complex, an E3 ubiquitin ligase. The uba-1
      mutation provides a sensitized genetic background for identifying new in vivo
      functions for downstream components of the ubiquitin enzyme cascade, and it is
      one of the first conditional mutations reported for the essential E1 enzyme in a
      metazoan animal model.

PMID- 18636106
TI  - Inefficient Nef-mediated downmodulation of CD3 and MHC-I correlates with loss of
      CD4+T cells in natural SIV infection.
AB  - Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect
      SIVsmm-infected sooty mangabeys (SMs) against the loss of CD4+ T cells. However,
      the mechanisms underlying this protective effect remain unclear. To further
      assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from
      11 SIVsmm-infected SMs with high (>500) and 15 animals with low (<500) CD4+ T
      cells/microl in bulk into proviral HIV-1 IRES/eGFP constructs and analyzed their
      effects on the phenotype, activation, and apoptosis of primary T cells. We found
      that not only efficient Nef-mediated downmodulation of TCR-CD3 but also of MHC-I
      correlated with preserved CD4+ T cell counts, as well as with high numbers of
      Ki67+CD4+ and CD8+CD28+ T cells and reduced CD95 expression by CD4+ T cells.
      Moreover, effective MHC-I downregulation correlated with low proportions of
      effector and high percentages of naive and memory CD8+ T cells. We found that T
      cells infected with viruses expressing Nef alleles from the CD4low SM group
      expressed significantly higher levels of the CD69, interleukin (IL)-2 and
      programmed death (PD)-1 receptors than those expressing Nefs from the CD4high
      group. SIVsmm Nef alleles that were less active in downmodulating TCR-CD3 were
      also less potent in suppressing the activation of virally infected T cells and
      subsequent cell death. However, only nef alleles from a single animal with very
      low CD4+ T cell counts rendered T cells hyper-responsive to activation, similar
      to those of HIV-1. Our data suggest that Nef may protect the natural hosts of SIV
      against the loss of CD4+ T cells by at least two mechanisms: (i) downmodulation
      of TCR-CD3 to prevent activation-induced cell death and to suppress the induction
      of PD-1 that may impair T cell function and survival, and (ii) downmodulation of
      MHC-I to reduce CTL lysis of virally infected CD4+ T cells and/or bystander CD8+
      T cell activation.

PMID- 18636107
TI  - A precisely regulated gene expression cassette potently modulates metastasis and
      survival in multiple solid cancers.
AB  - Successful tumor development and progression involves the complex interplay of
      both pro- and anti-oncogenic signaling pathways. Genetic components balancing
      these opposing activities are likely to require tight regulation, because even
      subtle alterations in their expression may disrupt this balance with major
      consequences for various cancer-associated phenotypes. Here, we describe a
      cassette of cancer-specific genes exhibiting precise transcriptional control in
      solid tumors. Mining a database of tumor gene expression profiles from six
      different tissues, we identified 48 genes exhibiting highly restricted levels of
      gene expression variation in tumors (n = 270) compared to nonmalignant tissues (n
      = 71). Comprising genes linked to multiple cancer-related pathways, the
      restricted expression of this "Poised Gene Cassette" (PGC) was robustly validated
      across 11 independent cohorts of approximately 1,300 samples from multiple cancer
      types. In three separate experimental models, subtle alterations in PGC
      expression were consistently associated with significant differences in
      metastatic and invasive potential. We functionally confirmed this association in
      siRNA knockdown experiments of five PGC genes (p53CSV, MAP3K11, MTCH2, CPSF6, and
      SKIP), which either directly enhanced the invasive capacities or inhibited the
      proliferation of AGS cancer cells. In primary tumors, similar subtle alterations
      in PGC expression were also repeatedly associated with clinical outcome in
      multiple cohorts. Taken collectively, these findings support the existence of a
      common set of precisely controlled genes in solid tumors. Since inducing small
      activity changes in these genes may prove sufficient to potently influence
      various tumor phenotypes such as metastasis, targeting such precisely regulated
      genes may represent a promising avenue for novel anti-cancer therapies.

PMID- 18636108
TI  - Myc oncogene-induced genomic instability: DNA palindromes in bursal
      lymphomagenesis.
AB  - Genetic instability plays a key role in the formation of naturally occurring
      cancer. The formation of long DNA palindromes is a rate-limiting step in gene
      amplification, a common form of tumor-associated genetic instability. Genome-wide
      analysis of palindrome formation (GAPF) has detected both extensive palindrome
      formation and gene amplification, beginning early in tumorigenesis, in an
      experimental Myc-induced model tumor system in the chicken bursa of Fabricius. We
      determined that GAPF-detected palindromes are abundant and distributed
      nonrandomly throughout the genome of bursal lymphoma cells, frequently at
      preexisting short inverted repeats. By combining GAPF with chromatin
      immunoprecipitation (ChIP), we found a significant association between occupancy
      of gene-proximal Myc binding sites and the formation of palindromes. Numbers of
      palindromic loci correlate with increases in both levels of Myc over-expression
      and ChIP-detected occupancy of Myc binding sites in bursal cells. However, clonal
      analysis of chick DF-1 fibroblasts suggests that palindrome formation is a
      stochastic process occurring in individual cells at a small number of loci
      relative to much larger numbers of susceptible loci in the cell population and
      that the induction of palindromes is not involved in Myc-induced acute fibroblast
      transformation. GAPF-detected palindromes at the highly oncogenic bic/miR-155
      locus in all of our preneoplastic and neoplastic bursal samples, but not in DNA
      from normal and other transformed cell types. This finding indicates very strong
      selection during bursal lymphomagenesis. Therefore, in addition to providing a
      platform for gene copy number change, palindromes may alter microRNA genes in a
      fashion that can contribute to cancer development.

PMID- 18636109
TI  - Pituitary changes in Prop1 transgenic mice: hormone producing tumors and signet
      ring type gonadotropes.
AB  - Prophet of Pit-1 (Prop1) is an early transcription factor that delays the
      appearance of gonadotropin in the developing pituitaries. Prop1 transgenic (Tg)
      mice have been shown to generate pituitary tumors that either produce TSH or are
      non-hormone producing. In our series of Prop1 Tg mice, only 5 out of 9 female
      mice produced pituitary adenomas, and the adenomas were only GH, PRL, GH and PRL,
      PRL and gonadotropin or TSH producing. The pituitary cells that surrounded these
      adenomas showed hyperplasia of the corresponding hormone producing cells; i.e.
      the GH cells were increased in the pituitary that contained GH producing adenoma.
      In addition, although the adenomas lacked the expression of Prop1, the non
      neoplastic pituitary cells showed expression of Prop1. The Prop1 Tg mice also
      showed vacuolated cells with eccentric nuclei, which are characteristic of
      "signet-ring hypertrophic cells". Using immunohistochemistry, these signet ring
      hypertrophic cells were found to be positive for gonadotropin.Taken together, our
      results suggest a (1) tumorigenic effect of Prop1 in the pituitaries, and (2)
      causative effects of signet ring-type gonadotropes.

PMID- 18636110
TI  - Homeostatic mass control in gastric non-neoplastic epithelia under infection of
      Helicobacter pylori: an immunohistochemical analysis of cell growth, stem cells
      and programmed cell death.
AB  - We evaluated homeostatic mass control in non-neoplastic gastric epithelia under
      Helicobacter pylori (HP) infection in the macroscopically normal-appearing mucosa
      resected from the stomach with gastric cancer, immunohistochemically analyzing
      the proliferation, kinetics of stem cells and programmed cell death occurring in
      them. Ki67 antigen-positive proliferating cells were found dominantly in the
      elongated neck portion, sparsely in the fundic areas and sporadically in the
      stroma with chronic infiltrates. CD117 could monitor the kinetics of gastric stem
      cells and showed its expression in two stages of gastric epithelial
      differentiation, namely, in transient cells from the gastric epithelial stem
      cells to the foveolar and glandular cells in the neck portion and in what are
      apparently progenitor cells from the gastric stem cells in the stroma among the
      infiltrates. Most of the nuclei were positive for ssDNA in the almost normal
      mucosa, suggesting DNA damage. Cleaved caspase-3-positive foveolar cells were
      noted under the surface, suggesting the suppression of apoptosis in the surface
      foveolar cells. Besides such apoptosis of the foveolar cells, in the severely
      inflamed mucosa apoptotic cells were found in the neck portion where most of the
      cells were Ki67 antigen-positive proliferating cells. Beclin-1 was recognized in
      the cytoplasm and in a few nuclei of the fundic glandular cells, suggesting their
      autophagic cell death and mutated beclin-1 in the nuclei. Taken together, the
      direct and indirect effects of HP infection on the gastric epithelial
      proliferation, differentiation and programmed cell death suggested the in-situ
      occurrence of gastric cancer under HP infection.

PMID- 18636111
TI  - Thymidylate synthase, thymidine phosphorylase and orotate phosphoribosyl
      transferase levels as predictive factors of chemotherapy in oral squamous cell
      carcinoma.
AB  - We conducted a clinicopathologic study on protein and mRNA levels of thymidylate
      synthase (TS), thymidine phosphorylase (TP) and orotate phosphoribosyl
      transferase (OPRT) using biopsy tissue specimens before treatment. The mRNA
      levels have been measured in tumor cells microdissected from paraffin-embedded
      specimens (Danenberg Tumor Profile method: DTP method). We studied the mRNA and
      protein expression as effect predictive factors in chemotherapy. The subjects
      consisted of 20 cases of untreated oral squamous cell carcinoma who had undergone
      chemotherapy with TS-1 (16 males and 4 females, tongue in 8 cases, upper gingiva
      in 3 cases, lower gingiva in 3 cases, buccal mucosa in 5 cases and floor of the
      mouth in 1 case). TS gene expressions of the responders were lower than those for
      the nonresponders. Furthermore, regarding males who were less than 70 years of
      age, stage I and II, well differentiated type and tongue, TS mRNA expression of
      the responders were lower than that for the nonresponders. The mRNA expression of
      OPRT for the male responders was lower than that for the nonresponders. No
      remarkable difference was observed by immunohistochemistry. In this study, the
      measurement of the TS levels using the DTP method may potentially act as a
      predictive factor of antitumor effectiveness.

PMID- 18636112
TI  - Comparison of chromogenic in situ hybridisation with fluorescence in situ
      hybridisation and immunohistochemistry for the assessment of her-2/neu oncogene
      in archival material of breast carcinoma.
AB  - The successful treatment of breast cancer is dependent upon a number of complex
      factors. Her-2/neu gene amplification is known to be one of the most common
      genetic alterations associated with breast cancer and its accurate determination
      has become necessary for the selection of patients for trastuzumab therapy. The
      aim of this study was to prove the consistency of chromogenic in situ
      hybridisation (CISH) technique after analyzing the overexpression of the Her
      2/neu proto-oncogene in 100 invasive breast carcinomas and by comparing CISH
      results with immunohistochemistry (IHC) and fluorescence in situ hybridisation
      (FISH). Moreover, it was done to evaluate the possible correlation of estrogen
      (ERs) and progesterone receptors (PRs), the proliferation marker Ki67 and the
      tumour suppressor gene p53 with HER-2/neu status of these breast carcinomas. Of
      the 100 breast carcinomas that were analysed, 22 cases showed HER-2/neu
      amplification, 66 cases showed no amplification, whereas 12 cases were non
      interpretable in both assays (FISH and CISH). Consequently, the overall
      concordance between FISH and CISH was 100%. Additionally, it was observed that
      when HER-2/neu gene was overexpressed, there was an association with negative PRs
      and ERs status, negative p53 protein expression and high Ki67 labelling index. It
      is concluded that patients with tumours scoring 2+ with the CBE356 antibody
      (borderline immunohistochemistry-tested cases) would also benefit from CISH as it
      is shown to be highly accurate, practical and can be easily integrated into
      routine testing in any histopathology laboratory. Finally, CISH represents an
      important addition to the HER2 testing algorithm.

PMID- 18636114
TI  - Similarity queries for temporal toxicogenomic expression profiles.
AB  - We present an approach for answering similarity queries about gene expression
      time series that is motivated by the task of characterizing the potential
      toxicity of various chemicals. Our approach involves two key aspects. First, our
      method employs a novel alignment algorithm based on time warping. Our time
      warping algorithm has several advantages over previous approaches. It allows the
      user to impose fairly strong biases on the form that the alignments can take, and
      it permits a type of local alignment in which the entirety of only one series has
      to be aligned. Second, our method employs a relaxed spline interpolation to
      predict expression responses for unmeasured time points, such that the spline
      does not necessarily exactly fit every observed point. We evaluate our approach
      using expression time series from the Edge toxicology database. Our experiments
      show the value of using spline representations for sparse time series. More
      significantly, they show that our time warping method provides more accurate
      alignments and classifications than previous standard alignment methods for time
      series.

PMID- 18636113
TI  - Anti-fungal innate immunity in C. elegans is enhanced by evolutionary
      diversification of antimicrobial peptides.
AB  - Encounters with pathogens provoke changes in gene transcription that are an
      integral part of host innate immune responses. In recent years, studies with
      invertebrate model organisms have given insights into the origin, function, and
      evolution of innate immunity. Here, we use genome-wide transcriptome analysis to
      characterize the consequence of natural fungal infection in Caenorhabditis
      elegans. We identify several families of genes encoding putative antimicrobial
      peptides (AMPs) and proteins that are transcriptionally up-regulated upon
      infection. Many are located in small genomic clusters. We focus on the nlp-29
      cluster of six AMP genes and show that it enhances pathogen resistance in vivo.
      The same cluster has a different structure in two other Caenorhabditis species. A
      phylogenetic analysis indicates that the evolutionary diversification of this
      cluster, especially in cases of intra-genomic gene duplications, is driven by
      natural selection. We further show that upon osmotic stress, two genes of the nlp
      29 cluster are strongly induced. In contrast to fungus-induced nlp expression,
      this response is independent of the p38 MAP kinase cascade. At the same time,
      both involve the epidermal GATA factor ELT-3. Our results suggest that selective
      pressure from pathogens influences intra-genomic diversification of AMPs and
      reveal an unexpected complexity in AMP regulation as part of the invertebrate
      innate immune response.

PMID- 18636115
TI  - Lysyl oxidase-like 1 gene polymorphisms in Japanese patients with primary open
      angle glaucoma and exfoliation syndrome.
AB  - PURPOSE: To assess whether lysyl oxidase-like 1 (LOXL1) polymorphisms are
      associated with primary open-angle glaucoma (POAG) and exfoliation syndrome
      (XFS). METHODS: Japanese patients with POAG (n=213) or XFS (n=89) and 191 control
      subjects were analyzed for LOXL1 polymorphisms (rs1048661: 758G/T, Arg141Leu and
      rs3825942: 794G/A, Gly153Asp). Demographic and clinical features of POAG patients
      and control subjects were compared in terms of the TT/GG compound genotype of
      rs1048661 and rs3825942. RESULTS: There was a significant difference in the
      genotype frequencies between XFS patients and control subjects (p<0.0001).
      Frequencies of the T allele of rs1048661 and the G allele of rs3825942 were
      significantly higher in XFS patients than in control subjects (rs1048661: 99.4%
      versus 55.0%; rs3825942: 99.4% versus 85.3%; p<0.0001). Except for one who had
      the TG/AG compound genotype, all XFS patients had the TT/GG compound genotype. An
      almost 250 fold increase in the risk of XFS (p<0.0001; odds ratio: 252.2; 95%
      confidence interval: 32.7 to more than 1000) was found in patients with the TT/GG
      compound genotype compared to those without the genotype. There were no
      significant differences in the genotype and allele frequencies between POAG
      patients and control subjects. Furthermore, no significant differences were noted
      in the demographic and clinical features of POAG patients as well as control
      subjects with and without the TT/GG high-risk compound genotype. CONCLUSIONS:
      LOXL1 polymorphisms were associated with XFS. However, the frequencies of the
      polymorphisms differed between Japanese and Caucasian XFS patients. These
      polymorphisms had no influence on the phenotypic features of POAG patients.

PMID- 18636117
TI  - CNGA3 mutations in two United Arab Emirates families with achromatopsia.
AB  - PURPOSE: ACHROMATOPSIA RESULTS FROM MUTATIONS IN ONE OF THREE GENES: cyclic
      nucleotide-gated channel, alpha-3 (CNGA3); cyclic nucleotide-gated channel, beta
      3 (CNGB3); and guanine nucleotide-binding protein, alpha-transducing activity
      polypeptide 2 (GNAT2). We report the responsible mutations in two United Arab
      Emirates families who have this autosomal recessive disease. METHODS: Clinical
      examinations were performed in seven patients from three nuclear families.
      Molecular genetic testing for common CNGA3 and CNGB3 mutations was undertaken
      using standard protocols. RESULTS: All patients were extremely light sensitive
      and had reduced visual acuity and no color perception. Fundus examinations did
      not show any visible abnormalities. After further pedigree analysis, two of the
      families were found to be linked through the paternal line. Two mutations in
      CNGA3 were identified: Arg283Trp and Gly397Val. Family A, the larger pedigree,
      had one branch in which two sisters and one brother were homozygous for the
      Gly397Val mutation and another branch in which a brother and sister were compound
      heterozygous for both aforenamed mutations. Family B, however, only had two
      brothers who were homozygous for the Arg283Trp mutation. CONCLUSIONS:
      Achromatopsia in these two United Arab Emirates families results from two
      different mutations in CNGA3. Two branches of the same pedigree had individuals
      with both homozygous and compound heterozygous disease, demonstrating a complex
      molecular pathology in this large family.

PMID- 18636116
TI  - Evaluation of EGR1 as a candidate gene for high myopia.
AB  - PURPOSE: EGR1 (OMIM 128990) is an early growth response gene that has been shown
      to be related to myopia by upregulation and down-regulation of axial eye growth
      in experimentally induced chicken myopia and knockout mice. The purpose of this
      study was to test whether variations in the human EGR1 gene are related to high
      myopia. METHODS: Genomic DNA was prepared from leukocytes of peripheral blood.
      Cycle sequencing was used to detect sequence variations in EGR1. RESULTS: No
      pathological mutations were detected upon sequencing of the coding regions and
      the adjacent intronic regions of EGR1 in 96 unrelated Chinese subjects with high
      myopia. Only one silent variation, c.1026G>A (p.V342V), was detected in one
      patients with high myopia, which would not affect the encoded protein. For all 96
      subjects, only one allele was detected in each of the three known single
      nucleotide polymorphisms (SNPs) in EGR1. CONCLUSIONS: We found no evidence that
      EGR1 is responsible for high myopia in these patients.

PMID- 18636118
TI  - Host-derived oxidized phospholipids and HDL regulate innate immunity in human
      leprosy.
AB  - Intracellular pathogens survive by evading the host immune system and accessing
      host metabolic pathways to obtain nutrients for their growth. Mycobacterium
      leprae, the causative agent of leprosy, is thought to be the mycobacterium most
      dependent on host metabolic pathways, including host-derived lipids. Although
      fatty acids and phospholipids accumulate in the lesions of individuals with the
      lepromatous (also known as disseminated) form of human leprosy (L-lep), the
      origin and significance of these lipids remains unclear. Here we show that in
      human L-lep lesions, there was preferential expression of host lipid metabolism
      genes, including a group of phospholipases, and that these genes were virtually
      absent from the mycobacterial genome. Host-derived oxidized phospholipids were
      detected in macrophages within L-lep lesions, and 1 specific oxidized
      phospholipid, 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3
      phosphorylcholine (PEIPC), accumulated in macrophages infected with live
      mycobacteria. Mycobacterial infection and host-derived oxidized phospholipids
      both inhibited innate immune responses, and this inhibition was reversed by the
      addition of normal HDL, a scavenger of oxidized phospholipids, but not by HDL
      from patients with L-lep. The accumulation of host-derived oxidized phospholipids
      in L-lep lesions is strikingly similar to observations in atherosclerosis, which
      suggests that the link between host lipid metabolism and innate immunity
      contributes to the pathogenesis of both microbial infection and metabolic
      disease.

PMID- 18636119
TI  - Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node
      function and connexin 45 localization in the murine heart.
AB  - The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that
      belongs to the family of adhesion molecules. In the postnatal heart, it is
      localized predominantly at the intercalated disc, where its function is not
      known. Here, we demonstrate that a first degree or complete block of
      atrioventricular (AV) conduction developed in the absence of CAR in the adult
      mouse heart and that prolongation of AV conduction occurred in the embryonic
      heart of the global CAR-KO mouse. In the cardiac-specific CAR-KO (CAR-cKO) mouse,
      we observed the loss of connexin 45 localization to the cell-cell junctions of
      the AV node but preservation of connexin 40 and 43 in contracting myocardial
      cells and connexin 30.2 in the AV node. There was also a marked decrease in beta
      catenin and zonula occludens-1 (ZO-1) localization to the intercalated discs of
      CAR-cKO mouse hearts at 8 weeks before the mice developed cardiomyopathy at 21
      weeks of age. We also found that CAR formed a complex with connexin 45 via its
      PSD-95/DigA/ZO-1-binding (PDZ-binding) motifs. We conclude that CAR expression is
      required for normal AV-node conduction and cardiac function. Furthermore,
      localization of connexin 45 at the AV-node cell-cell junction and of beta-catenin
      and ZO-1 at the ventricular intercalated disc are dependent on CAR.

PMID- 18636120
TI  - Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling
      pathways and controls human and rat SMC proliferation.
AB  - The second messengers cAMP and cGMP can be degraded by specific members of the
      phosphodiesterase superfamily or by active efflux transporters, namely the
      multidrug resistance-associated proteins (MRPs) MRP4 and MRP5. To determine the
      role of MRP4 and MRP5 in cell signaling, we studied arterial SMCs, in which the
      effects of cyclic nucleotide levels on SMC proliferation have been well
      established. We found that MRP4, but not MRP5, was upregulated during
      proliferation of isolated human coronary artery SMCs and following injury of rat
      carotid arteries in vivo. MRP4 inhibition significantly increased intracellular
      cAMP and cGMP levels and was sufficient to block proliferation and to prevent
      neointimal growth in injured rat carotid arteries. The antiproliferative effect
      of MRP4 inhibition was related to PKA/CREB pathway activation. Here we provide
      what we believe to be the first evidence that MRP4 acts as an independent
      endogenous regulator of intracellular cyclic nucleotide levels and as a mediator
      of cAMP-dependent signal transduction to the nucleus. We also identify MRP4
      inhibition as a potentially new way of preventing abnormal VSMC proliferation.

PMID- 18636121
TI  - Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and
      brainstem development in mice.
AB  - Joubert syndrome is an autosomal recessive disorder characterized by congenital
      malformation of the cerebellum and brainstem, with abnormal decussation in the
      brain. Mutations in the Abelson helper integration site 1 gene, which encodes the
      protein AHI1, have been shown to cause Joubert syndrome. In this study, we found
      that mouse Ahi1 formed a stable complex with huntingtin-associated protein 1
      (Hap1), which is critical for neonatal development and involved in intracellular
      trafficking. Hap1-knockout mice showed significantly reduced Ahi1 levels,
      defective cerebellar development, and abnormal axonal decussation. Suppression of
      Ahi1 also decreased the level of Hap1; and truncated Ahi1, which corresponds to
      the mutations in Joubert syndrome, inhibited neurite outgrowth in neuronal
      culture. Reducing Hap1 expression suppressed the level and internalization of
      TrkB, a neurotrophic factor receptor that mediates neurogenesis and neuronal
      differentiation, which led to decreased TrkB signaling. These findings provide
      insight into the pathogenesis of Joubert syndrome and demonstrate the critical
      role of the Ahi1-Hap1 complex in early brain development.

PMID- 18636122
TI  - B cell receptor revision diminishes the autoreactive B cell response after
      antigen activation in mice.
AB  - Autoreactive B cells are regulated in the BM during development through
      mechanisms, including editing of the B cell receptor (BCR), clonal deletion, and
      anergy. Peripheral B cell tolerance is also important for protection from
      autoimmune damage, although the mechanisms are less well defined. Here we
      demonstrated, using a mouse model of SLE-like serology, that during an autoimmune
      response, RAG was reinduced in antigen-activated early memory or preplasma B
      cells. Expression of RAG was specific to antigen-reactive B cells, required the
      function of the IL-7 receptor (IL-7R), and contributed to maintenance of humoral
      tolerance. We also showed that soluble antigen could diminish a non-autoreactive
      antibody response through induction of BCR revision. These data suggest that
      tolerance induction operates in B cells at a postactivation checkpoint and that
      BCR revision helps regulate autoreactivity generated during an ongoing immune
      response.

PMID- 18636123
TI  - An atypical phenotype of Reis-Bucklers corneal dystrophy caused by the G623D
      mutation in TGFBI.
AB  - PURPOSE: To characterize the molecular defects in the TGFBI gene in a Chinese
      family with an unusual phenotype of Reis-Bucklers corneal dystrophy (RBCD).
      METHODS: Three generations of the family with RBCD were enrolled in the present
      study. In addition to ophthalmologic examinations, polymerase chain reaction
      (PCR) amplification and nucleotide sequencing of exons of TGFBI were performed.
      Exon 14 was also sequenced in 100 healthy controls unrelated to the family for
      comparison. RESULTS: The clinical features of the disease were characterized by
      geographic opacities in the anterior to mid stroma of the cornea. Molecular
      genetic analysis revealed a heterozygous point mutation at exon 14 (c.1915 G>A)
      in all affected members of the family. The unusual opacities involving the
      anterior to mid-cornea stroma were different from the phenotypic features of
      families previously reported to have the same genetic change. CONCLUSIONS: We
      speculate that this disorder is a variant of RBCD. This finding may expand our
      knowledge about RBCD and facilitate diagnosis of corneal dystrophies associated
      with atypical clinical features.

PMID- 18636125
TI  - [Professional education and pediatrics practice].

PMID- 18636124
TI  - Polymorphisms in the estrogen receptor 1 and vitamin C and matrix
      metalloproteinase gene families are associated with susceptibility to lymphoma.
AB  - BACKGROUND: Non-Hodgkin lymphoma (NHL) is the fifth most common cancer in the
      U.S. and few causes have been identified. Genetic association studies may help
      identify environmental risk factors and enhance our understanding of disease
      mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: 768 coding and haplotype tagging SNPs
      in 146 genes were examined using Illumina GoldenGate technology in a large
      population-based case-control study of NHL in the San Francisco Bay Area (1,292
      cases 1,375 controls are included here). Statistical analyses were restricted to
      HIV- participants of white non-Hispanic origin. Genes involved in
      steroidogenesis, immune function, cell signaling, sunlight exposure, xenobiotic
      metabolism/oxidative stress, energy balance, and uptake and metabolism of
      cholesterol, folate and vitamin C were investigated. Sixteen SNPs in eight
      pathways and nine haplotypes were associated with NHL after correction for
      multiple testing at the adjusted q<0.10 level. Eight SNPs were tested in an
      independent case-control study of lymphoma in Germany (494 NHL cases and 494
      matched controls). Novel associations with common variants in estrogen receptor 1
      (ESR1) and in the vitamin C receptor and matrix metalloproteinase gene families
      were observed. Four ESR1 SNPs were associated with follicular lymphoma (FL) in
      the U.S. study, with rs3020314 remaining associated with reduced risk of FL after
      multiple testing adjustments [odds ratio (OR) = 0.42, 95% confidence interval
      (CI) = 0.23-0.77) and replication in the German study (OR = 0.24, 95% CI = 0.06
      0.94). Several SNPs and haplotypes in the matrix metalloproteinase-3 (MMP3) and
      MMP9 genes and in the vitamin C receptor genes, solute carrier family 23 member 1
      (SLC23A1) and SLC23A2, showed associations with NHL risk.
      CONCLUSIONS/SIGNIFICANCE: Our findings suggest a role for estrogen, vitamin C and
      matrix metalloproteinases in the pathogenesis of NHL that will require further
      validation.

PMID- 18636126
TI  - [Mycoplasma pneumoniae: what is still out of our knowledge].

PMID- 18636127
TI  - [Seroprevalence of Mycoplasma pneumoniae in children aged under 12 years].
AB  - INTRODUCTION: Although Mycoplasma pneumoniae is usually assumed as an infection
      mainly prevalent in school aged children and adolescents, there is evidence
      supporting that it may occur at younger ages. This could be related to social
      conditions, like crowding and day care center/school attendance more frequently
      and at younger ages than two decades ago. We estimated the prevalence of
      antibodies anti- Mycoplasma pneumoniae in children aged under 12 years. We also
      evaluated its association with age, day care center/school attendance, crowding
      or other children in the household. POPULATION AND METHODS: This cross-sectional
      study included children aged under 12 years that required blood sampling for
      surgery. Those with acute infections, chronic diseases or known immunological
      disorders were excluded. In all cases predictors were recorded, and IgG anti
      Mycoplasma pneumoniae determined by enzimoimmunoassay. Association between
      predictors and seropositivity was evaluated by logistic regression. RESULTS: We
      included 355 children, aged 4.8 +/- 3.1 years. 57.6% attended to day care
      center/school, crowding was present in 27.3% and 70.1% had other children in the
      household. IgG antibodies anti-Mycoplasma pneumoniae were present in 12.4%.
      Seropositives were older than seronegatives (7.1 +/- 3.15 years vs. 4.4 +/- 3.06
      years, p < 0.0001). After controlling by confounders, age remains as an
      independent predictor of seropositivity (OR: 1.19, CI 95%: 1.043-1.362).
      CONCLUSIONS: Seroprevalence of Mycoplasma pneumoniae IgG antibodies in children
      aged under 12 years was 12.4%. Age is an independent predictor of seropositivity.

PMID- 18636128
TI  - [Children and adolescent's drawing for the diagnosis of migraine].
AB  - INTRODUCTION: Migraine is frequent in children. Children's drawings of their
      symptoms can help to identify it. OBJECTIVE: To evaluate the accuracy of
      children's drawings to identify migraine in those who suffer from headache.
      POPULATION, MATERIALS AND METHODS: We evaluated 48 patients aged 5 to 19 years,
      assisted for headache. In all cases they were asked to draw what happened to them
      before and during the episode, and then the drawing was analyzed by a pediatric
      neurologist ("artistic diagnosis"). Afterwards, all were evaluated by another
      pediatric neurologist ("clinical diagnosis"). Sensitivity (Se), specificity (Sp),
      negative (NPV) and positive (PPV) predictive values of the "artistic diagnosis"
      to predict "clinical diagnosis" were calculated. Possible interaction of age,
      Intellectual Standard Score (ISS), maternal education and previous contact with a
      neurologist was evaluated by logistic regression. RESULTS: After controlling by
      those factors, the "artistic diagnosis" was found to be an independent predictor
      of the "clinical diagnosis" of migraine (p < 0.01, OR: 23), achieving Se: 69,6%,
      Sp: 88%, PPV: 84,2% and NPV: 75,9. The performance was still better when only
      subjects with ISS >/= 70 were considered. CONCLUSION: Children tend to
      communicate their symptoms more effectively through drawings than verbally. The
      "artistic diagnosis" was accurate to predict the "clinical diagnosis" of
      migraine.

PMID- 18636129
TI  - [Flexible bronchoscopy in a pediatric pulmonology service].
AB  - INTRODUCTION: Flexible bronchoscopy is a valuable diagnostic and therapeutic
      tool. The objective of the study is to describe the experience with flexible
      bronchoscopy in a Pulmonology Section of a Pediatric tertiary care hospital
      associated to the university. POPULATION AND METHODS: Studies performed between
      01/2002 and 12/2005 were reviewed. Olympus(R) bronchoscopes (external diameters
      2.8 and 4.8 mm) were used. Bronchoalveolar lavage was performed with 3 aliquots
      of 1 ml/kg of warmed sterile saline solution. RESULTS: One hundred and two
      fiberoptic bronchoscopies (49 males, 42 outpatients) and 77 bronchoalveolar
      lavage were performed. Patient's age ranged from 2 months to 18 years. Fifty one
      studies were done in an endoscopy suite, 47 in the operating room and 4 in the
      intensive care unit. Patient's diagnosis were: chronic lung disease (recurrent/
      persistent pneumonia, bronchiectasis, primary ciliary dyskinesia) 65% (n: 66);
      immune deficiencies 18% (n: 18); cystic fibrosis 7% (n: 7), difficult airway 5%
      (n: 6) and noisy breathing 5% (n: 5). Ten patients developed mild complications
      (7 hypoxemia, 2 upper airway obstruction, 1 cardiac arrhythmia), and 1 patient a
      severe one (severe bronchial obstruction). Eighty five (65/77) bronchoalveolar
      lavage samples, 100% (12/12) bronchial brushing and 100% (6/6) endobronchial
      biopsies were representative. Procedures helped the decision-making process in
      75% (76/102) of the patients studied. CONCLUSIONS: In this carefully selected
      population, flexible bronchoscopy and bronchoalveolar lavage were useful for
      their diagnosis and treatment.

PMID- 18636130
TI  - [Therapeutic monitoring of vancomycin in critical care pediatric patients].
AB  - INTRODUCTION: Vancomycin is used in pediatric patients usually at 40 mg/kg/day
      four times daily. Recent data demonstrated the need of large doses to reach
      therapeutic concentrations in critical patients. OBJECTIVE: Describe dosage
      regime of vancomycin in patients from a pediatric intensive care unit, register
      values of plasmatic concentrations and determine the regimes necessary to reach
      therapeutic troughs. POPULATION, MATERIALS AND METHODS: We made an observational,
      retrospective study. Patients who received vancomycin by more than two days where
      studied. Patients who didn't register vancomycin troughs (minimum values) and/or
      with elevated serum creatinine were excluded. The age, grouping in younger than
      (<) 2 years and older than (>) 2 years and troughs of vancomycin were registered.
      Volume of distribution (Vd) and half-life (t 1/2) were obtained. Results. We
      studied 97 patients. Patients with undetectable plasmatic concentrations younger
      than two years were 14 and the older ones were 9, this difference was not
      statistically significant (p= 0.063). Mediam of the regime of administration for
      the younger group was 50 mg/kg/day each 6 h and for the older 40 mg/kg/day four
      times a day. Mediam (range) of Vd and half-life (t 1/2) for the group of < 2
      years and >2 years were 0.682 (0.504-1.06) L/kg, 6.12 (2.66-17.49) h; 0.685
      (0.389-1.198) L/kg, 4.88 (3.59-15.4) h, without significant differences.
      CONCLUSIONS: Dosage regime required an increase in frequency, in addition there
      were no significant differences between pharmacokinetic parameters and final
      administration regime for both groups, being able to suppose that equal schemes
      of administration could be implemented more frequently.

PMID- 18636131
TI  - [Videothoracoscopic sympathicolysis procedure for primary palmar hyperhidrosis in
      children and adolescents].
AB  - INTRODUCTION: The endoscopic thoracic sympathicolysis procedure is a chirurgical
      technique used in the treatment of the primary palmar hyperhidrosis. POPULATION,
      MATERIAL AND METHODS: Descriptive and retrospective study of 25 patients with
      diagnosis of palm and palm-axilar hyperhidrosis surgically intervened in a period
      of 4 years in three private institutions of Gran Buenos Aires. The age ranged
      between 8-18 years. In all of the cases the surgery consisted in the endoscopic
      thoracic sympathicolysis of the T2-T3 ganglion. The operation was made in both
      sides and in one surgical time. There were considered for this study the age,
      sex, intra- and post-surgical complications, side effects, efficacy of the
      procedure and the grade of patients satisfaction. RESULTS: Hyperhidrosis
      disappeared in 98% of the patients. Besides the improvement of palmar excessive
      sweating, diminution of axilar perspiration was found in 16 patients, and in the
      feet in 6 patients. The rate of post-operating complications was 20% and all were
      transitory. Three patients showed a subcutaneous emphysema that resolved in 24-48
      hours. One patient referred important pain 24 hours and one patient referred pain
      in the puncture zone that improved with common analgesic until it disappeared in
      three months. About the satisfaction with the procedure, 22 patients declared to
      be very satisfied, two were satisfied and one moderately satisfied. CONCLUSIONS:
      The primary palmar hyperhidrosis is a pathology that entails an important
      reduction in the quality of life of those who suffer it. The results obtained
      with this technique allow recommending the endoscopic thoracic sympathicolysis
      procedure for the treatment of this pathology in pediatrics.

PMID- 18636132
TI  - [The infant of diabetes mother dilemma: Changes, past, present and future].

PMID- 18636133
TI  - [SUNCT syndrome (short-lasting unilateral neuralgiform headache with conjuntival
      injection and tearing): a rare case in a paediatric patient with favourable
      response to topiramate].
AB  - SUNCT Syndrome (short-lasting unilateral neuralgiform headache with conjuntival
      injection and tearing) combines neuralgic, migraineus and autonomic headaches,
      three of four primary ones described in the International Classification of the
      IHS (International Headache Society). This work describes a paediatric case
      evaluated under MIDAS score in which a new therapeutic approach with topiramate
      (TPM) was used.

PMID- 18636134
TI  - [Dermatopathy associated with levamisole-induced reversible posterior
      leukoencephalopathy].
AB  - Levamisole is an antihelmintic drug that stimulates antibodies formation
      increasing both T response, and neutrophilic response, and quimiotaxis. It is
      used in dermatology for the treatment of plane warts, erythema multiforme,
      aphtous ulcers and, with prednisone, in lichen planus. With prolonged use this
      drug has been implicated in adverse dermatological reactions as lichenoid
      eruptions, ulcers and vasculitis. We present a 9-years old girl who developed a
      cutaneous eruption and a reverse leucoencephalopathy with a short treatment but
      high doses of the drug.

PMID- 18636135
TI  - [Munchausen syndrome by proxy and presumed apparent life-threatening event
      manifestations].

PMID- 18636136
TI  - [Exanthema, fever and adenopathies: make your diagnosis].

PMID- 18636137
TI  - [The commitment of medical societies with social events].

PMID- 18636139
TI  - [Recommendation for the use of umbilical cord blood: Intended for perinatal care
      teams].

PMID- 18636138
TI  - [Consensus on Bronchial Asthma. 2007: 1st. part].

PMID- 18636140
TI  - [Recommendations for Retinopathy of Prematurity screening in at-risk
      populations].

PMID- 18636142
TI  - Cancer genomics and genetics of FGFR2 (Review).
AB  - FGFR2 gene encodes FGFR2b in epithelial cells, and FGFR2c in mesenchymal cells.
      FGFR2b is a high affinity receptor for FGF1, FGF3, FGF7, FGF10 and FGF22, while
      FGFR2c for FGF1, FGF2, FGF4, FGF6, FGF9, FGF16 and FGF20. Here genomics and
      genetics of FGFR2, and therapeutics targeted to FGFR2 will be reviewed. Single
      nucleotide polymorphisms (SNPs) of FGFR2 are associated with increased risk of
      breast cancer. Gene amplification or missense mutation of FGFR2 occurs in gastric
      cancer, lung cancer, breast cancer, ovarian cancer, and endometrial cancer.
      Genetic alterations of FGFR2 induce aberrant FGFR2 signaling activation due to
      release of FGFR2 from autoinhibition, or creation of FGF signaling autocrine
      loop. Class switch of FGFR2b to FGFR2c is associated with more malignant
      phenotype. FGF and canonical WNT signals synergize during mammary carcinogenesis,
      but counteract during osteogenesis and adipogenesis. Among PD173074, SU5402, and
      AZD2171 functioning as FGFR inhibitors, AZD2171 is the most promising anti-cancer
      drug. Cancer genomics and genetics are utilized to predict cancer-driving pathway
      for therapeutic optimization. FGFR2ome is defined as a complete data set of SNP,
      copy number variation (CNV), missense mutation, gene amplification, and
      predominant isoform of FGFR2. FGFR2ome analyses in patients with several tumor
      types among various populations should be carried out to establish integrative
      database of FGFR2 for the rational clinical application of FGFR2-targeted cancer
      therapy.

PMID- 18636144
TI  - Minichromosome maintenance protein 7 in colorectal cancer: implication of
      prognostic significance.
AB  - Minichromosome maintenance (MCM) proteins are essential components for DNA
      replication, and also prognostic markers for various human tumors. MCM-positive
      but Ki67-negative cells (e.g. primary oocytes) are thought to be licensed non
      proliferating populations, and are significantly correlated with the
      clinicopathological profiles of some human tumors. In the present study, we
      evaluated the expression levels of MCM7, MCM2 and Ki67 in colorectal cancer to
      clarify their pathobiological significance. We carried out Western blot analyses
      of 5 human colorectal cancer cell lines and performed immunohistochemistry on 202
      surgically removed colorectal cancers of Dukes' B and C stages. Double-labeling
      immunofluorescence was also carried out on the cancer specimens to identify MCM
      positive but Ki67-negative tumor cells. MCM proteins were detected in all the 5
      cell lines examined. MCM7 and MCM2 were coexpressed in almost the same
      populations of tumor cells, whereas MCM7-negative but Ki67-positive tumor cells
      were absent in the double-labeled specimens, except for mitotic cells. The mean
      positive tumor labeling indexes (LIs) for MCM7, MCM2 and Ki67 were 58.1, 57.1 and
      40.6%, respectively. The mean LI for MCM7-positive but Ki67-negative tumor cells
      was 17.6%, and significantly correlated with the N status (P=0.01), distant
      metastasis (P=0.01) and UICC stage (P=0.02). The high LI of >58.1% for MCM7 were
      independent prognostic factors in multivariate Cox regression analysis (relative
      risk = 2.12; P=0.02). Our results indicate that MCM7 expression is an independent
      prognostic factor for human colorectal cancer, and MCM7-positive but Ki67
      negative tumor cells are correlated with tumor metastases.

PMID- 18636145
TI  - VEGF blockade decelerates the growth of a murine experimental osteosarcoma.
AB  - Retrovirus-mediated sFlt-1 gene modification was performed to examine the
      influence of VEGF in controlling the growth of an experimental osteosarcoma in
      mice. Human osteosarcoma G-292 cells were in vitro infected with retroviral
      vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal
      tibiae of immune deficient SCID mice to establish experimental orthotopic
      osteosarcoma. Daily observation and biweekly microCT were performed to monitor
      tumor development and progression till sacrifice at 8 weeks after tumor cell
      inoculation for histological and molecular analyses. Successful transgene
      expression was confirmed in the culture media of sFlt-1 transduced G-292 cells
      using ELISA, and with positive X-gal staining of the LacZ transduced cells.
      Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell
      inoculation, with clear detection on microCT images starting 2 weeks after
      inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292
      cells were distinctively smaller in size when compared to the ones from wide-type
      G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics
      including severe cellular pleomorphism, bone erosions, and neo-vascularization.
      Real-time polymerase chain reaction indicated significantly higher sFlt-1
      expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ-treated
      groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along
      with the expression of VEGF in the primary tumor tissue. Overall, data suggest
      that retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma
      tumor growth in this murine model.

PMID- 18636143
TI  - Central review of cytogenetics is necessary for cooperative group correlative and
      clinical studies of adult acute leukemia: the Cancer and Leukemia Group B
      experience.
AB  - The Cancer and Leukemia Group B has performed central review of karyotypes
      submitted by institutional cytogenetics laboratories from patients with acute
      myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the
      role of central karyotype review in maintaining accurate, high quality
      cytogenetic data for clinical and translational studies using two criteria: the
      proportion of karyotypes rejected (i.e. inadequate), and, among accepted (i.e.
      adequate) cases, the proportion of karyotypes whose interpretation was changed on
      central karyotype review. We compared the first four years during which central
      karyotype review was performed with a recent 4-year period and found that the
      proportion of rejected samples decreased significantly for both AML and ALL.
      However, during the latter period, central karyotype reviews still found 8% of
      AML and 16% of ALL karyotypes inadequate. Among adequate cases, the karyotype was
      revised in 26% of both AML and ALL samples. Some revisions resulted in changing
      the patients' assignment to particular World Health Organization diagnostic
      categories and/or moving patients from one prognostic group to another. Overall,
      when both data on rejection rates and data on karyotype revisions made in
      accepted cases were considered together, 32% of AML and 38% of ALL samples
      submitted were either rejected or revised on central karyotype review during the
      recent 4-year period. These data underscore the necessity of continued central
      karyotype review in multi-institutional cooperative group studies.

PMID- 18636146
TI  - Identification of novel deletion polymorphisms in breast cancer.
AB  - Breast cancer is the most frequent cancer in females worldwide and it has long
      been known that multiple genetic rearrangements correlate with complex biology
      and clinical behavior. In addition, copy number variations (CNVs) of DNA
      sequences account for a significant proportion of normal phenotypic variation and
      may have an important role in human pathological variation. In this study, we
      carried out a high-density oligonucleotide array comparative genomic
      hybridization (CGH) analyses in a series of breast cancer cell lines to identify
      novel homozygous deletion loci. The results were confirmed by quantitative PCR (Q
      PCR) and 4 genes, the REV1L, ZNF14, NPAS1 and APOBEC3B genes, were selected.
      Analyses of 30 microdissected human breast tumors and paired normal mammary
      tissue samples indicated that these homozygous deletions are small-scale deletion
      polymorphisms. The variation in copy number at the loci of the 4 genes in blood
      derived DNA demonstrated the frequency of deletions including homozygous
      deletions and single copy variants to be higher in breast cancer patients than
      healthy females. Notably, the homozygous deletion of APOBEC3B involved part of
      exon 5 and seemed to be cancer-specific in some patients, indicating that this is
      a functionally important structural variant. These copy number changes may play
      an important role in breast cancer and array-CGH analyses can thus be expected to
      provide new insight into the genetic background of breast cancer.

PMID- 18636147
TI  - Germline and somatic c-met mutations in multifocal/bilateral and sporadic
      papillary renal carcinomas of selected patients.
AB  - Papillary renal carcinoma (PRC) comprises about 10% of all kidney epithelial
      tumors. Familiar/hereditary papillary renal carcinomas (HPRCs) have been
      described, but the majority of cases seem to be sporadic. HPRC is characterized
      by the predisposition to develop bilateral, multifocal renal tumors. Activating
      mutations in the tyrosine kinase domain (TK) of the hepatocyte growth factor
      (HGF) receptor, c-met, have been identified in both hereditary and sporadic PRC.
      The main aim of this study was to examine a family with no history of PRC in
      which the proband was a female patient affected by multiple and bilateral PRC at
      early onset. DNA mutation analysis has been performed by direct sequencing of
      exons 14-21 of c-met gene which include the TK domain. The proband displayed the
      germline c-met missense mutation g.3522G--> A in exon 16. Two other family
      members were found to carry the same mutation. The mutation analysis extended to
      15 selected patients, allowed to identify the first case of an Italian patient
      affected by PRC displaying the somatic missense mutation g.3997 T-->C curved
      arrow C located in exon 19 of c-met. The mutation frequency of the selected-based
      population of PRC patients in this report was 12.5%. Furthermore, the
      phosphorylated c-met expression detected by immunohistochemistry in PRCs with
      germline/somatic or no c-met mutation, supports the concept that c-met activation
      may occur in PRC oncogenesis by c-met mutations and/or c-met over-expression.

PMID- 18636148
TI  - Evaluation of the potential anti-cancer activity of the antidepressant sertraline
      in human colon cancer cell lines and in colorectal cancer-xenografted mice.
AB  - Evidence has been provided of the anti-proliferative activity of certain
      antidepressants, mainly the selective serotonin reuptake inhibitors (SSRIs). We
      tested the effect of different antidepressants on cell viability and
      proliferation of human colorectal carcinoma cell lines HT29 and the multi-drug
      resistant (MDR) LS1034. The SSRIs, paroxetine and sertraline, induced a dose
      dependent inhibition of cell viability and proliferation in the two cell lines
      (IC50 8-15 micro M). When compared to cytotoxic agents e.g. doxorubicin,
      vincristine and 5-fluorouracil, the SSRIs showed comparable activity (HT29) or a
      superior effect (LS1034). Using flow cytometry analysis, we found that the two
      SSRIs arrested cells at the G0/G1 stage and stimulated DNA fragmentation in a
      dose-dependent manner. The SSRIs (10 and 20 microM) increased caspase-3
      activation. Western blot analysis showed an increase after 24 h in c-Jun and a
      decrease in the expression of the anti-apoptotic protein Bcl-2. The results
      suggest a proapoptotic activity for the active SSRIs accompanied by mitogen
      activated protein kinase cascade activation and Bcl-2 inhibition. In vivo, we
      used CD1 nude mice xenografted subcutaneously with HT29 cells. On day 8, after
      cell inoculation sertraline or paroxetine (15 mg/kg x3/week i.p.) were
      administered to animals (6/group), which were monitored weekly (for 5 weeks) for
      tumor volume and body weight. At 5 weeks, the animals survived, with no
      significant difference in body weight. Sertraline, though not paroxetine,
      significantly inhibited tumor growth. Collectively, our results suggest that the
      widely-used antidepressant, sertraline, possesses a potential anti-tumor
      activity, which circumvents the MDR mechanism. Since SSRI therapy is frequently
      indicated in cancer patients, the use of sertraline in colon cancer patients with
      co-morbidity of depression seems attractive.

PMID- 18636149
TI  - The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular
      carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction
      pathways.
AB  - The A3 adenosine receptor (A(3)AR) is highly expressed in tumors and was
      suggested as a target for cancer treatment. In this study, we show that A(3)AR is
      highly expressed in tumor tissues and in peripheral blood mononuclear cells
      (PBMCs) derived from patients with HCC, as well as from HCC tumor-bearing rats.
      The high expression level of the receptor was directly correlated to
      overexpression of NF-kappaB, known as a transcription factor of A(3)AR. CF102, a
      synthetic highly selective agonist to A(3)AR induced a marked dose response
      inhibition of tumor growth in N1S1 HCC tumor rats, via de-regulation of the NF
      kappaB and the Wnt signal transduction pathways, resulting in apoptosis of tumor
      cells. Taken together, A(3)AR is highly expressed in tumors and PBMCs of HCC
      patients and tumor-bearing rats. CF102 induced apoptosis and tumor growth
      inhibition. These data suggest A(3)AR as a novel targeted therapy to treat HCC.

PMID- 18636150
TI  - Expression and potential function of the CXC chemokine CXCL16 in pancreatic
      ductal adenocarcinoma.
AB  - CXC chemokines have a major influence on the angiogenesis, growth and metastatic
      potential of pancreatic ductal adenocarcinoma. CXCL16 is a unique transmembrane
      CXC chemokine, which is shed by members of the disintegrins and metalloproteases
      (ADAMs), in particular by ADAM10 and ADAM17. In our study, we evaluated
      expression and potential function of CXCL16 and its receptor CXCR6. CXCL16 and
      the receptor CXCR6 are upregulated in pancreatic ductal adenocarcinoma (PDAC) and
      chronic pancreatitis tissues in contrast to normal pancreatic tissues at the mRNA
      and protein levels. In 85 and 100% of the investigated samples, tumor cells
      showed positive immuno-staining for CXCL16 and CXCR6, respectively; furthermore,
      tubular complexes of chronic pancreatitis and the invasive front of PDAC were
      immunopositive for CXCL16 and CXCR6. Stimulation of PDAC cells with
      proinflammatory cytokines increased CXCL16 protein levels, whereas silencing of
      ADAM10 with siRNA transfection led to a decrease in CXCL16 protein levels in cell
      culture supernatants. No effects on cell viability were notable after incubation
      of cancer cells with CXCL16. However, CXCL16 markedly increased invasiveness of
      PDAC cells. Clinically, 82.5% of PDAC patients had higher CXCL16 serum values
      than the highest value seen in healthy donors. SELDI-TOF-MS analysis confirmed
      the upregulation of CXCL16 in sera of PDAC patients. In conclusion, CXCL16 in
      both transmembrane and soluble forms, and its receptor CXCR6, seem to play an
      important role in the pathobiology of pancreatic cancer and might be potential
      markers for pancreatic cancer diagnosis and a target for multimodal therapy
      concepts in the future.

PMID- 18636151
TI  - Cell motility affects the intensity of gap junctional coupling in prostate
      carcinoma and melanoma cell populations.
AB  - Connexins and gap junctions play a crucial role during carcinogenesis. While
      diverse regulatory systems have been shown to modulate their function, the
      influence of cell motility on the intensity of gap junctional intercellular
      coupling has yet to be systematically addressed. Since cancer cell motility and
      intercellular coupling determine cancer development, we aimed at elucidating how
      mutual cell translocation modulates the intensity of gap junctional coupling in
      cell populations. Time-lapse analyses of the motility of connexin43 (Cx43)
      coupled rat prostate carcinoma (MAT-LyLu) and mouse melanoma (B16) cells cultured
      on hyper-adhesive substrata revealed a reduced intensity of intercellular
      translocations in the two cell populations compared to the control conditions.
      While no detectable effects on the architecture of the actin cytoskeleton and
      Cx43 expression and phosphorylation were observed, the inhibition of cell
      motility was paralleled by an increase in the abundance of Cx43-positive plaques
      in cell-to-cell contacts and an enhancement of gap junctional coupling in cell
      populations cultured on hyper-adhesive substrata. Thus, a direct correlation
      between two cellular parameters crucial for carcinogenesis, i.e. cell motility
      and gap junctional coupling intensity exists in cancer cell populations.

PMID- 18636152
TI  - Prevention and delay in progression of human pancreatic cancer by stable
      overexpression of the opioid growth factor receptor.
AB  - This study examined overexpression of the opioid growth factor receptor (OGFr) in
      pancreatic cancer cells and phenotypic changes in tumorigenicity. Tumors of MIA
      PaCa-2 cells transfected with OGFr cDNA (OGFr-1) had 3.3 times more OGFr than
      empty vector (EV) neoplasias, and 4.3 times more OGFr than tumors from wild-type
      (WT) mice. No differences in OGFr binding were detected between tumors of EV and
      WT animals. Tumor incidence in OGFr-1 animals was reduced by up to 50% from EV
      mice. Latency times for OGFr-1 tumor expression were increased 30%, tumor volume
      was decreased 70%, and DNA synthesis was reduced 24% relative to EV mice.
      Exogenous OGF reduced OGFr-1 tumor volume up to 55% compared to OGFr-1 mice given
      vehicle. These data support OGFr gene function as a regulator of cell
      proliferation that impacts on tumorigenic expression, and suggest that molecular
      and pharmacological manipulation of OGFr may prevent or delay human pancreatic
      cancer.

PMID- 18636153
TI  - The role of oxidative stress in apoptosis induced by the histone deacetylase
      inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29
      cells.
AB  - Histone deacetylase inhibitors (HDACIs) activate genes that promote cell cycle
      arrest and apoptosis in a number of tumor cells. This study showed that
      suberoylanilide hydroxamic acid (SAHA), a potent and commonly used HDACI, induced
      apoptosis in human colon adenocarcinoma HT-29 cells in a time- and dose-dependent
      manner. This effect was accompanied by the induction of oxidative stress,
      dissipation of mitochondrial transmembrane potential and activation of
      executioner caspases. Moreover, SAHA increased the levels of phosphorylated
      active forms of p38 and JNK. The addition of either the antioxidant N
      acetylcysteine or the specific inhibitor of NADPH oxidase diphenylene iodonium
      chloride reduced the cytotoxic effects of SAHA in HT-29 cells, suggesting that
      the induction of oxidative stress represents a crucial event in the apoptotic
      mechanism. In addition, SAHA up-regulated the death receptor DR5, inducing the
      activation of caspase-8 with the consequent cleavage of Bid. Furthermore, SAHA
      down-regulated FLIPL and Akt, two proteins which exert an inhibitory role in
      apoptosis.

PMID- 18636154
TI  - Role of menin in the regulation of telomerase activity in normal and cancer
      cells.
AB  - Transcriptional activation of human telomerase reverse transcriptase (hTERT) is
      critical for telomerase expression, a major step for cellular immortality and
      carcinogenesis. Although several transcriptional activators have been identified,
      factors responsible for repressing the hTERT promoter are largely unknown. Gene
      screening that employed enhanced retroviral mutagenesis has identified potential
      hTERT repressors. Among these, menin, which is a tumor suppressor and a gene
      product of MEN1, has been reported to play a critical role. In the present study,
      we further analyzed menin's role in the transcriptional regulation of hTERT in
      normal and cancer cells. Luciferase reporter assays that use the hTERT promoter
      have demonstrated that an overexpression of menin decreases the transcriptional
      activity of the hTERT gene in a cell-type specific manner. Mutation and deletion
      analyses of the hTERT promoter demonstrated that there was no specific site on
      the promoter that was responsible for the menin-mediated transcriptional
      inhibition. An electrophoretic mobility shift assay using recombinant menin
      protein generated the binding complexes with the hTERT promoter, which was
      completely diminished by the addition of poly-dI-dC. This indicates that there is
      a sequence-independent binding of menin. RT-PCR assays have revealed that
      overexpression of menin inhibits hTERT mRNA expression in some cell types,
      although this inhibition does not lead to a significant down-regulation of
      telomerase activity. In cancer cell lines and in normal cells, the siRNA-based
      inhibition of MEN1 does not lead to the up-regulation of hTERT mRNA expression.
      No significant correlation has been found between menin and hTERT mRNA
      expressions in a variety of cancer cell lines and clinical tissue samples. Thus,
      while menin appears to have some inhibitory effects on the hTERT promoter,
      possibly via the sequence-independent binding to the promoter, the present study
      does not support the hypothesis that menin has a crucial role in the
      determination of telomerase activity in normal and cancer cells.

PMID- 18636155
TI  - Effects of radiation on growth of two human tumour cell lines surviving a
      previous high dose, low dose-rate, radionuclide exposure.
AB  - Effects of radiation on growth of two human tumour cell lines that survived a
      previous high dose, low dose-rate radionuclide exposure simulating intensive
      radionuclide therapy, were analyzed. The purpose was to investigate whether the
      survivors gained therapy induced changes in growth and radiation response. The
      U118MG, ParRes (parental resistant), and U373MG, ParSen (parental sensitive),
      glioma cells were used because they are known to be low dose-rate radiation
      resistant and sensitive, respectively. These cells were initially exposed to high
      dose, low dose-rate radiation for 24 h and surviving U118MG and U373MG cells
      formed new cultures called SurRes (surviving resistant) and SurSen (surviving
      sensitive), respectively. All four cell types were then exposed to graded acute
      radiation doses, 0-8 Gy, and analyzed for radiation induced growth disturbances.
      They were also analyzed regarding DNA-content and cell cycle distributions. The
      SurRes cells regained in most cases the same growth rate, had the same growth
      delays and showed generally a similar response as the original ParRes cells to
      the 0-8 Gy exposures. In contrast, the SurSen cells had in all cases slower
      growth rate and longer growth delays than the original ParSen cells after the 0-8
      Gy exposures. There were no signs of radiation-induced radioresistance. The slow
      growing SurSen cells contained about 80% more DNA and had more cells in G1 and
      fewer in G2 than the ParSen cells. The conclusion is that tumour cells surviving
      high dose, low dose-rate, radionuclide therapy, afterwards can react differently
      to a new radiation exposure.

PMID- 18636156
TI  - Changes in expression of imprinted genes following treatment of human cancer cell
      lines with non-mutagenic or mutagenic carcinogens.
AB  - It remains possible that chemicals that act by mutagenic mechanisms as well as
      chemicals that do not induce gene mutations may affect epigenetic gene
      expression. To test the possibility, we investigated the ability of both types of
      chemicals to alter the expression of five imprinted genes, PEG3, SNRPN, NDN, ZAC
      and H19, using two human colon cancer cell lines and a human breast cancer cell
      line. The expression of imprinted genes was changed by some non-mutagenic and
      mutagenic carcinogens independent of their mutagenic activity. The genes most
      commonly exhibiting the changes in expression were SNRPN and PEG3. Alterations of
      the expression of NDN and ZAC were also observed in some conditions. Methylation
      specific PCR and chromatin immunoprecipitation assays suggest the possibility
      that changes in the expression of SNRPN may be associated with DNA
      hypomethylation and histone acetylation of the promoters and euchromatinization
      of the heterochromatic domains of the promoters. Changes in expression of the
      imprinted genes, PEG3 and NDN, were also observed in cells immortalized by
      treatment of normal human fibroblasts with 4-nitroquinoline 1-oxide or aflatoxin
      B1. We previously demonstrated that expression of the cancer-related gene, INK4a,
      in these immortal cells was lost via epigenetic mechanisms. The results prove
      that, in cancer cells, some mutagenic or non-mutagenic carcinogens can
      epigenetically influence the transcription levels of imprinted genes and also
      suggest the possibility that some chemical carcinogens may have epigenetic
      carcinogenic effects in human cells.

PMID- 18636157
TI  - Proteomic analysis of the basic proteins in 5-fluorouracil resistance of human
      colon cancer cell line using the radical-free and highly reducing method of two
      dimensional polyacrylamide gel electrophoresis.
AB  - 5-Fluorouracil (5-FU) is widely used for the treatment of patients with advanced
      colon cancers and it is the mainstay of chemotherapy. However, the acquisition of
      resistance to 5-FU is one of the most prominent obstacles to successful
      chemotherapy. The purpose of this study was to identify the novel biological
      basis of 5-FU resistance in colon cancer cells. This study is the first
      comparative proteomic analysis of basic proteins between the DLD-1 human colon
      cancer cell line and DLD-1/5-FU its 5-FU resistant sub-line using the radical
      free and highly reducing method of two-dimensional polyacrylamide gel
      electrophoresis, which has a superior ability in the separation of basic proteins
      and the quantification of post-translational modification. A densitometric
      analysis was performed to quantify the modulated proteins, and protein spots
      showing significant changes were identified by matrix-assisted laser
      desorption/ionization time-of-flight/time-of-flight mass spectrometry. Six basic
      proteins significantly modulated between DLD-1 and DLD-1/5-FU were identified.
      All of them showed up-regulated expression in DLD-1/5-FU in comparison to DLD-1.
      The six identified spots, corresponding to five different proteins included
      heterogeneous nuclear ribonucleoprotein G, mitochondrial transcription factor A,
      histone H2B, histone H4 and ribosomal protein L3. Among the 5 basic proteins,
      several proteins are potentially related to 5-FU resistance by protecting the
      cells from DNA damage.

PMID- 18636158
TI  - Aberrant expression of B203.13 antigen in acute lymphoid leukemia of B-cell
      origin.
AB  - The B203.13 monoclonal antibody was developed by immunizing mice with the
      B/monocyte biphenotypic cell line B1b. During normal hematopoiesis B203.13 is
      expressed on a fraction of CD34+ cells, while on mature cells it is only present
      on B-lymphocytes. We tested this antibody as a marker of childhood B-acute
      lymphoblastic leukemia (B-ALL). Bone marrow aspirates from 139 cases of early B
      ALL and 25 controls were studied. About 40% of the B-ALL patients expressed
      B203.13. In these patients, B203.13 was constantly co-expressed with CD10, but
      never co-expressed with CD20, contrary to the controls. The CD10(+)/B203.13(+)
      phenotype was specific to B-ALL, since CD10(+)/CD20(+) cells from common acute
      lymphoblastic leukemia (c-ALL) did not express B203.13. We concluded that the use
      of B203.13 in association with CD10 and CD20 provides meaningful information for
      distinguishing normal residual B-cells from leukemic B-lymphoblasts and that
      recurrence of a CD10(+)/B203.13(+) phenotype after transplantation may be a very
      early relapse indicator of early B-acute lymphoblastic leukemia.

PMID- 18636160
TI  - Downmodulation of dimethyl transferase activity enhances tumor necrosis factor
      related apoptosis-inducing ligand-induced apoptosis in prostate cancer cells.
AB  - One of the major obstacles in curing prostate cancer is the development of drug
      resistance. It is not only imperative to discover the molecular basis of
      resistance but also to find therapeutic agents that can disrupt the resistant
      pathways. Tumor necrosis factor TNF-related apoptosis-inducing ligand TRAIL-like
      ligands or agonist TRAIL-receptor monoclonal antibodies have entered phase I and
      II clinical trials with a very limited cytotoxic profile when used systemically
      in a variety of cancers. Therefore, TRAIL-receptor agonists are new proapoptotic
      pharmaceutical agents with great potential as new cancer therapeutic agents.
      Although many cancer cells undergo TRAIL-mediated apoptosis, some are resistant
      to TRAIL. Therefore, we have been investigating mechanisms to overcome TRAIL
      resistance in cancer cells so that TRAIL-associated compounds can be used
      effectively in clinical trials. Epigenetic inactivation of proapoptotic genes, or
      activation of survival signaling, can cause cross-resistance to several anti
      tumor therapies and to immune cytotoxic lymphocytes. We hypothesize that 5-aza-2
      deoxycytidine aza-dCR, decitabine may render TRAIL-resistant prostate cancer
      cells sensitive to caspase-8-mediated apoptosis and may, therefore, be
      therapeutically efficient. We evaluated the antiproliferative effects of
      decitabine on the following four prostate cancer cell lines: well-differentiated
      AR positive LnCaP p53(+), PTEN- and 22rv1 p53(+) and PTEN(+)]; poorly
      differentiated AR negative PC3 p53-, PTEN- and DU145 p53 mutant, PTEN(+). Here,
      we provide evidence that treatment with sub-optimal concentrations of decitabine
      are additive to TRAIL effects in well-differentiated PCa cells whereas the same
      treatment shows synergistic effects in poorly-differentiated PCa cells through
      increased caspase-8 expression, down-modulation of Akt activation and through the
      expression of certain anti-apoptotic molecules including FLIP, PED/PEA-15,
      survivin and c-IAP-1. Our findings demonstrate that decitabine at relatively low
      concentrations restores caspase-8 expression and sensitises resistant PCa cells
      to TRAIL-induced apoptosis leading to important implications in novel therapeutic
      strategies targeting defective apoptosis pathways in advanced prostate tumors.

PMID- 18636159
TI  - De-repression of the p21 promoter in prostate cancer cells by an isothiocyanate
      via inhibition of HDACs and c-Myc.
AB  - Natural isothiocyanates from cruciferous vegetables have been described as
      important dietary factors for prostate cancer prevention. Phenethyl
      isothiocyanate (PEITC), found rich in watercress, induces growth arrest and
      apoptosis in prostate cancer cells, and also inhibits the testosterone-mediated
      growth of prostates by regulating the androgen receptor and cell cycle
      progression in rats. PEITC has been recently identified as an inhibitor of
      histone deacetylases (HDACs). Herein we describe the mechanism of PEITC-mediated
      growth attenuation in relation to HDAC inhibition in human prostate cancer cells.
      Exposure of androgen-dependent prostate cancer cells LNCaP to PEITC resulted in
      cell cycle arrest and a p53-independent up-regulation of the inhibitors of cyclin
      dependent kinases, including p21WAF1 and p27. The mechanism of p21 activation was
      investigated. PEITC significantly enhanced histone acetylation and induced
      selective modification of histone methylation for chromatin remodeling. Chromatin
      immunoprecipitation revealed that the p21 gene was associated with the PEITC
      induced hyperacetylated histones. As a result, the chromatin unfolding permitted
      the transcription activation of the p21 gene. PEITC also significantly reduced
      the expression of c-Myc which represses p21. Pull-down assays using Sp1 affinity
      oligo beads of the p21 promoter, showed decreased c-Myc binding to the Sp1
      transcriptional complexes in the p21 promoter, resulting in reduced p21
      repression. The quantity of PEITC (0.5-1 micro M) effective to mediate cell cycle
      arrest was less than that for inhibiting c-Myc (2-5 micro M), suggesting that the
      inhibition of HDACs may be the primary mechanism for p21 activation. The PEITC
      mediated growth attenuation of prostate cancer cells includes an interactive
      mechanism involving HDAC and c-Myc inhibition.

PMID- 18636161
TI  - The association of deamidation of Bcl-xL and translocation of Bax to the
      mitochondria through activation of JNK in the induction of apoptosis by treatment
      with GSH-conjugated DXR.
AB  - We investigated the induction of apoptosis via deamidation of Bcl-xL and
      translocation of Bax to the mitochondria by treatment with GSH-DXR. GSH-DXR
      treatment of HepG2 cells, which did not express GST P1-1, exhibited deamidation
      of Bcl-xL, and the degree of deamidation was related to the activation of caspase
      3. Overexpression of GST P1-1 in HepG2 cells decreased both the Bcl-xL
      deamidation and caspase-3 activation induced by treatment with GSH-DXR. Bcl-xL
      deamidation and caspase-3 activation were also suppressed by co-treatment with
      SP600125, a specific inhibitor of JNK activity. Overexpression of wild-type Bcl
      xL in HepG2 decreased GSH-DXR-induced apoptosis although deamidation was
      observed. However, expression of the deamidated mutant of Bcl-xL, in which
      aspartic acid was substituted for both arginine 52 and 66 (N52,66D-Bcl-xL),
      exhibited high sensitivity for the induction of apoptosis. Expression of the Bcl
      xL mutant, in which alanine was substituted for both arginine 52 and 66 (N52,66A
      Bcl-xL), suppressed deamidation and showed resistance to the induction of
      apoptosis by treatment with GSH-DXR. On the other hand, endogenous Bax and
      overexpressed Flag-Bax were localized in the cytosolic fraction of HepG2 cells.
      Treatment of the cells with GSH-DXR caused translocation of Flag-Bax to the
      mitochondrial fraction following the induction of apoptosis. The induced
      apoptosis was enhanced by the expression of Flag-Bax. Moreover, Flag-Bax was
      partly located in the mitochondrial fraction in N52,66D-Bcl-xL-expressed cells
      without the induction of apoptosis. Therefore, the induction of apoptosis by
      treatment of HepG2 with GSH-DXR was enhanced, thereby facilitating the release of
      cytochrome c by both deamidated inactivation of Bcl-xL and functional
      translocation of Bax to the mitochondria via JNK activation. Deamidation of Bcl
      xL might be induced in order to translocate Bax to the mitochondria.

PMID- 18636163
TI  - Gonadotropin-releasing hormone agonists suppress melanoma cell motility and
      invasiveness through the inhibition of alpha3 integrin and MMP-2 expression and
      activity.
AB  - Cutaneous melanoma represents the leading cause of skin cancer deaths. The
      prognosis of highly aggressive, metastatic melanoma is still very poor, due to
      the resistance of the disseminated tumor to existing therapies. The clarification
      of the molecular mechanisms regulating melanoma growth and progression might help
      identify novel molecular targets for the development of new therapeutic
      interventions. We previously showed that gonadotropin-releasing hormone (GnRH)
      receptors are expressed in melanoma cells; activation of these receptors by means
      of GnRH agonists significantly reduces cell proliferation. In the current study,
      we first showed that GnRH agonists significantly reduced the metastatic behavior
      of melanoma cells in terms of both cell motility (haptotactic assay using laminin
      as the chemoattractant) and invasiveness (cell invasion assay evaluating the
      capacity of the cells to invade a reconstituted extracellular matrix barrier). On
      the basis of this observation, we then investigated the molecular mechanisms
      underlying the antimetastatic activity of GnRH agonists. We found that, in
      melanoma cells, a) the activity of the alpha3 integrin subunit is crucial for the
      migratory behavior of the cells; b) GnRH agonists significantly reduced alpha3
      integrin expression (Western blotting and immunofluorescence studies); c) GnRH
      agonists significantly reduced MMP-2 expression (comparative RT-PCR) and activity
      (zymographic analysis performed on cell culture media). These data indicate that
      GnRH agonists, in addition to the previously reported antiproliferative effect,
      elicit a strong inhibitory activity on the migratory/invasive behavior of
      melanoma cells expressing GnRH receptors. These compounds reduce the metastatic
      potential of melanoma cells by interfering with the expression/activity of cell
      adhesion molecules (alpha3 integrin) and matrix metalloproteinase (MMP-2).

PMID- 18636162
TI  - G0S2 is an all-trans-retinoic acid target gene.
AB  - All-trans-retinoic acid (RA) treatment of acute promyelocytic leukemia (APL)
      cases expressing the t(15;17) product, PML/RARalpha, is a successful example of
      differentiation therapy. Uncovering RA target genes is of considerable interest
      in APL. This study comprehensively examines in APL cells transcriptional and post
      transcriptional regulation of the novel candidate RA target gene, G0S2, the G0/G1
      switch gene. Reverse transcription (RT)-polymerase chain reaction (PCR) and
      heteronuclear PCR assays performed +/- treatment with the protein synthesis
      inhibitor cycloheximide (CHX) revealed G0S2 induction within 3 h of RA-treatment.
      Treatment with the RNA synthesis inhibitor actinomycin D did not implicate G0S2
      transcript stabilization in the RA-mediated increase of G0S2 mRNA expression.
      Promoter elements of G0S2 were cloned into a reporter plasmid and retinoic acid
      receptor (RAR) co-transfection assays confirmed transcriptional activation after
      RA-treatment. Consistent with G0S2 being a direct RA target gene, retinoic acid
      response element (RARE) half-sites were found in this promoter. Mutation of these
      sites blocked RA-transcriptional activation of G0S2. To extend analyses to the
      protein expression level, a polyclonal anti-G0S2 antibody was derived and
      detected murine and human G0S2 species. G0S2 protein was rapidly induced in
      cultured NB4-S1 human APL cells and in APL transgenic mice treated with RA. An
      RAR pan-antagonist confirmed dependence on RARs for this induction. That these
      findings are clinically relevant was shown by analyses of APL cells derived
      directly from patients. These leukemic cells induced both a prominent increase in
      the cellular differentiation marker nitrotetrazolium blue (NBT) staining and
      marked increase in G0S2 expression. Taken together, these findings indicate G0S2
      is an RA target gene. The functional role of G0S2 in retinoid response of APL
      warrants further study.

PMID- 18636164
TI  - Stress-associated hormone, norepinephrine, increases proliferation and IL-6
      levels of human pancreatic duct epithelial cells and can be inhibited by the
      dietary agent, sulforaphane.
AB  - In current literature there is evidence that psychological factors can affect the
      incidence and progression of some cancers. Data obtained from animal models
      support the hypothesis that stress can be a cofactor. The underlying mechanisms
      for the association between psychological factors and pancreatic cancer are very
      poorly understood. In this study, we examined the possible growth promoting
      effects of the stress-associated hormone, norepinephrine, on immortalized human
      pancreatic duct epithelial cells. Our results suggest that norepinephrine can
      increase cell proliferation of human pancreatic duct epithelial cells. We also
      evaluated the ability of norepinephrine to induce interleukin-6 (IL-6),
      interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). All of
      which may promote oncogenesis of immortalized human pancreatic duct epithelial
      cells. We found that norepinephrine can increase the IL-6 and VEGF but not IL-10
      levels secreted by human pancreatic duct epithelial cells. Since norepinephrine
      can increase cell proliferation of human pancreatic duct epithelial cells, we
      performed further testing to see if dietary agents, sulforaphane and resveratrol,
      can inhibit norepinephrine-mediated increases in cell proliferation in human
      pancreatic duct epithelial cells. Interestingly, our results demonstrated that
      sulforaphane but not resveratrol inhibits norepinephrine-mediated increases in
      cell viability in human pancreatic duct epithelial cells. Furthermore,
      sulforaphane also inhibits norepinephrine-mediated increase of the IL-6 levels
      but not VEGF levels. Our study is the first to demonstrate that stress-associated
      hormone, norepinephrine, can increase the cell proliferation and IL-6 levels of
      human pancreatic duct epithelial cells, which can be inhibited by sulforaphane, a
      chemopreventive agent and a natural compound from the Cruciferous vegetables.

PMID- 18636165
TI  - Efficacy of reovirus therapy combined with cyclophosphamide and gene-modified
      cell vaccines on tumors induced in mice by HPV16-transformed cells.
AB  - Oncolytic virotherapy is a novel approach to cancer treatment. In the present
      study we tested the ability of reovirus type 3, strain Dearing, to suppress the
      growth of tumors induced in mice by HPV16-transformed TC-1 cells. In vitro, these
      cells are highly susceptible to the virus. In repeated in vivo tests the
      intratumoral inoculation of the virus resulted in only a minor slow-down of tumor
      growth, never in a complete cure. The effect of the treatment was not enhanced by
      the simultaneous administration of non-oncogenic, genetically modified TC-1 cells
      expressing either IL-2, IL-12 or GM-CSF, and, in fact, the oncolytic effect of
      the virus was even less expressed in some instances. When cyclophosphamide was
      used in combination with the viral treatment, a synergistic effect resulting in
      tumor suppression was observed. In most instances the tumor regression was
      transitory, however, and was followed by tumor progression. The outcome of these
      experiments was dependent on the timing of the two treatments.

PMID- 18636166
TI  - In silico study of a novel gene evolved from an ancestral SVIP gene and highly
      expressed in the adult mouse testes.
AB  - We found that a cDNA clone isolated from a mouse testis cDNA library, 1700015G11
      (Mmu_15G11), corresponded to the most highly expressed testis-specific mRNA in
      the adult mouse. Although the Mmu_15G11 cDNA is predicted to encode a small
      protein consisting of 67 amino acid residues, it has not yet been functionally
      annotated and has been designated as an unclassifiable clone. Since the Mmu_15G11
      protein possibly has a pivotal role in spermatogenesis, we initiated an in silico
      study of this clone, and revealed that an ancestral gene of 15G11 genes evolved
      from an ancestral gene for mammalian small valosin-containing protein-interacting
      protein (SVIP) genes by gene duplication. Although SVIP protein reportedly
      participates in endoplasmic reticulum-related protein degradation, 15G11 protein
      is predicted to be a nuclear protein and possibly participates in the interaction
      between proteins and nuclear DNA.

PMID- 18636167
TI  - Circadian rhythm disorder of thrombosis and thrombolysis-related gene expression
      in apolipoprotein E knock-out mice.
AB  - Plaque rupture and subsequent embolism as well as thrombosis are major causes of
      acute myocardial infarction and stroke secondary to atherosclerosis. Pai-1, t-PA,
      TF and ET-1 are thrombosis- and thrombolysis-related factors which play important
      roles in thrombosis formation and plaque rupture. Since acute myocardial
      infarction and stroke are more likely to occur between 6 a.m. and 12 p.m. than at
      another time of the day, we studied the relationship between circadian rhythm and
      Pai-1, t-PA, TF and ET-1 in normal and atherosclerotic mice. Atherosclerosis was
      developed in apoE-/- mice fed a normal diet or a high cholesterol diet. The
      expression of Pai-1, t-PA, TF and ET-1 in the hearts of control C57BL/6J mice and
      atherosclerotic mice was measured by real-time RT-PCR at different Zeitgeber
      times (ZT) including ZT0, ZT4, ZT8, ZT10, ZT12, ZT14, ZT16 and ZT20. The
      expression of Pai-1, t-PA, TF and ET-1 peaked between ZT14 and ZT16 and bottomed
      at ZT10 in C57BL/6J mice. Their expression in apoE-/- mice fed a normal diet lost
      circadian rhythm. Their expression in apoE-/- mice fed a high cholesterol diet
      peaked at ZT4, indicating a reverse circadian rhythm. Our result indicates that
      circadian changes in the expression of Pai-1, t-PA, TF and ET-1 may be involved
      in the onset of myocardial infarction and stroke.

PMID- 18636168
TI  - Inflammatory cytokine signaling in insulin producing beta-cells enhances the
      colocalization correlation coefficient between L-type voltage-dependent calcium
      channel and calcium-sensing receptor.
AB  - The immunological processes in type 1 diabetes and metabolic/inflammatory
      disorder in type 2 diabetes converge on common signaling pathway(s) leading to
      beta-cell death in these two diseases. The cytokine-mediated beta-cell death
      seems to be dependent on voltage-dependent calcium channel (VDCC)-mediated Ca2+
      entry. The Ca2+ handling molecular networks control the homeostasis of [Ca2+]i in
      the beta-cell. The activity and membrane density of VDCC are regulated by several
      mechanisms including G protein-coupled receptors (GPCRs). CaR is a 123-kDa seven
      transmembrane extracellular Ca2+ sensing protein that belongs to GPCR family C.
      Tumor necrosis factor-alpha (TNF-alpha), is a cytokine widely known to activate
      nuclear factor-kappaB (NF-kappaB) transcription in beta-cells. To obtain a better
      understanding of TNF-alpha-induced molecular interactions between CaR and VDCC,
      confocal fluorescence measurements were performed on insulin-producing beta-cells
      exposed to varying concentrations of TNF-alpha and the results are discussed in
      the light of increased colocalization correlation coefficient. The insulin
      producing beta-cells were exposed to 5, 10, 20, 30, and 50 ng/ml TNF-alpha for 24
      h at 37 degrees . The cells were then immunolabelled with antibodies directed
      against CaR, VDCC, and NF-kappaB. The confocal fluorescence imaging data showed
      enhancement in the colocalization correlation coefficient between CaR and VDCC in
      beta-cells exposed to TNF-alpha thereby indicating increased membrane delimited
      spatial interactions between these two membrane proteins. TNF-alpha-induced
      colocalization of VDCC with CaR was inhibited by nimodipine, an inhibitor of L
      type VDCC thereby suggesting that VDCC activity is required for spatial
      interactions with CaR. The 3-D confocal fluorescence imaging data also
      demonstrated that addition of TNF-alpha to RIN cells led to the translocation of
      NF-kappaB from the cytoplasm to the nucleus. Such molecular interactions between
      CaR and VDCC in tissues possibly provide control over Ca2+ channel activity via
      direct protein-protein contact.

PMID- 18636169
TI  - Common polymorphisms in the cannabinoid CB2 receptor gene (CNR2) are not
      associated with myocardial infarction and cardiovascular risk factors.
AB  - Myocardial infarction (MI) is a complex disease. Multiple genes and their
      interaction with various environmental factors influence the pathogenesis of MI
      that is thought to be tightly regulated by inflammatory pathways. Recent progress
      in genetic analysis includes the use of large-scale genome-wide association
      studies that have proven to be powerful tools even in the analysis of
      multifactorial phenotypes. However, certain genes are only sparsely represented
      on the available gene chips and additional candidate gene approaches are
      necessary. One such example is the CNR2 gene, encoding the cannabinoid receptor 2
      (CB2), which has been implicated in mediating anti-inflammatory and anti
      atherosclerotic effects in vivo. We therefore hypothesized that genetic
      variations within the CNR2 gene are associated with the development of MI or
      classic cardiovascular risk factors. In a large case-control study, 1,968
      individuals from the German MI family study were examined with 13 single
      nucleotide polymorphisms (SNPs) covering CNR2 and the adjacent genes. The
      association of these SNPs with MI or cardiovascular risk factors, such as
      arterial hypertension, obesity, hypercholesterolemia and diabetes mellitus, was
      determined. In allelic and genotypic models, none of the SNPs showed a
      significant association with MI. Separate analyses for men and women revealed no
      gender-specific relationship between common genetic variations within the CNR2
      gene and MI. Moreover, no significant association between CNR2 gene variants and
      common cardiovascular risk factors was observed. We therefore provide evidence in
      a large German population that common polymorphisms within the CNR2 gene confer
      no susceptibility to MI or to cardiovascular risk factors.

PMID- 18636170
TI  - Molecular analysis of mitochondrial gene mutations in Korean patients with
      nonsyndromic hearing loss.
AB  - Mutations in mitochondrial DNA (mtDNA) are a major cause of hearing loss. In this
      study, we performed a systematic mutational screening of the 12S rRNA, tRNA
      Ser(UCN), tRNA Lys and tRNA Leu(UUR) genes in 227 unrelated patients with
      nonsyndromic hearing impairment for the first time in a Korean population. We
      found two individuals with an A1555G mutation, which is a frequency (0.9%) lower
      than that of other East Asians. Furthermore, two novel variants (C895T and 961-CC
      insertion) in the 12S rRNA gene were identified in the affected individuals, but
      were absent in 217 controls, indicating that they may play a role in the
      pathogenesis of hearing loss. Notably, 961delT and T1005C mutations were
      identified at similar frequencies in both patients and control subjects. Our data
      suggest that these variants seem to be polymorphisms rather than causes of
      disease. On the other hand, we did not find any of the known deafness-associated
      mutations in these tRNA genes. These data suggest that the 12S rRNA gene may be a
      hot spot for mitochondrial mutations causing hearing loss in the Korean
      population.

PMID- 18636171
TI  - Bifidobacterium infantis suppresses proinflammatory interleukin-17 production in
      murine splenocytes and dextran sodium sulfate-induced intestinal inflammation.
AB  - Interleukin (IL)-17 acts as a potent inflammatory cytokine, and IL-17-producing
      cells (Th17 cells) have received much attention. However, the involvement of
      commensal and/or probiotic bacteria in IL-17 production has not been evaluated.
      In this study, we examined the suppressive effects of five bacteria species on IL
      17 production in vitro and ex vivo. Among the five species studied,
      Bifidobacterium infantis inhibited IL-17 production but enhanced IL-27 production
      most potently in TGF-beta plus IL-6-stimulated murine splenocytes. B. infantis
      also inhibited IL-17 and eotaxin production from a dextran sodium sulfate-treated
      colon organ culture. The induction of IL-10 by B. infantis was observed both in
      the splenocytes and in the colon culture and was assumed, to a certain extent, to
      be important for suppressing IL-17 production. These findings suggest a novel
      immunomodulatory function of commensal bifidobacteria and further imply that
      these bacteria may be useful in the treatment of Th17-mediated diseases.

PMID- 18636172
TI  - Evaluation of PRL-3 expression, and its correlation with angiogenesis and
      invasion in hepatocellular carcinoma.
AB  - Protein phosphatase of regenerating liver 3 (PRL-3) is a metastasis-associated
      phosphatase. Studies have shown that its overexpression increases cell motility
      and invasiveness. In this study, we aimed to investigate the expression of PRL-3
      in hepatocellular carcinoma (HCC) tumor tissues and determine its correlations
      with matrix metalloproteinases (MMP-2, MMP-9) and E-cadherin in HCC. Paired
      cancerous and non-cancerous tissues were freshly collected from 42 primary HCC
      patients. PRL-3 expression at both mRNA and protein level was evaluated by real
      time PCR, Western blot analysis and immunohistochemistry. The microvessel density
      (MVD) in HCC was detected with immunohistochemistry. The mRNA expression of MMP
      2, MMP-9 and E-cadherin was analyzed by real-time PCR in search of correlations
      with PRL-3. We found that PRL-3 was significantly up-regulated in the HCC tumor
      tissues compared with corresponding noncancerous liver tissues (0.664+/-0.053 vs.
      0.024+/-0.003, P<0.001). The mRNA level of PRL-3 in tissues was correlated with
      serum alpha-fetoprotein level, vascular invasion and metastasis (P<0.001). PRL-3
      expression was closely related to MVD. Furthermore, we found a significant
      correlation between PRL-3 mRNA expression and MMP-2, MMP-9 and E-cadherin. Our
      results demonstrated that PRL-3 is up-regulated in HCC. It is strongly suggested
      that PRL-3 plays a key role in the angiogenesis and invasion of HCC. MMP-2, MMP-9
      and E-cadherin might be involved in PRL-3 functions in HCC.

PMID- 18636173
TI  - Melagenine modulates proliferation and differentiation of melanoblasts.
AB  - Melagenine, extracted from human placenta, has been shown to be effective in
      treating patients with vitiligo, yet the mechanisms of melagenine in inducing the
      repigmentation of vitiligo patients have not been fully investigated. Recent
      studies have suggested that melagenine stimulates melanocyte proliferation and
      melanogenesis. In this study, we utilized the NCCmelb4M5 melanoblast cell line to
      investigate the effects of melagenine on proliferation and differentiation of
      immature melanocytes or melanoblasts. NCCmelb4M5 cells were treated with
      different concentrations of melagenine (50-400 microg/ml), and MTT assay was
      performed to evaluate the effects of melagenine on proliferation of melanoblasts.
      RT-PCR and Western blotting were used to determine the expression of c-KIT and
      tyrosinase (TYR). Our results show that melagenine stimulates proliferation of
      NCCmelb4M5 cells in a dose-dependent manner with an optimal concentration of 100
      microg/ml. Multipolar and highly branched dendritic network, as well as cluster
      like growing cell assembly were visible in melagenine-treated NCCmelb4M5 cells.
      Melagenine induced expression of c-KIT, TYR and MITF. Our results provide
      insights into the molecular mechanism of the beneficial effect of melagenine in
      the treatment of vitiligo.

PMID- 18636174
TI  - M-RIP, a novel target of JNK signaling and a requirement for human cancer cell
      invasion.
AB  - Cell motility is involved in physiological and pathological processes such as the
      invasion and migration of cells. c-Jun N-terminal kinase (JNK) cascades are
      involved in the invasion and metastasis of cancer cells. However, little is known
      about the downstream signaling of JNK. In the present study, we used small
      interfering RNA (siRNA) directed against JNK1 to reduce its expression. We used
      microarray techniques to compare the gene expression profiles of epidermal growth
      factor (EGF)-stimulated HeLa cells with and without JNK1 siRNA treatment. We
      identified a JNK1 target gene, myosin phosphatase-Rho interacting protein (M
      RIP). RNA interference-mediated inhibition of JNK1 strongly inhibited M-RIP mRNA
      expression induced by EGF, as well as the invasion of HeLa cells. In addition, M
      RIP siRNA-treated cells showed significantly reduced invasive activity. Thus, a
      functional analysis of JNK1 and M-RIP with RNA interference reveals a critical
      role for this cascade in the invasive behavior of cancer cells.

PMID- 18636175
TI  - Glucosamine suppresses interleukin-8 production and ICAM-1 expression by TNF
      alpha-stimulated human colonic epithelial HT-29 cells.
AB  - Intestinal epithelial cells play an important role in the mucosal immune reaction
      in inflammatory bowel diseases via the production and expression of chemokines
      and adhesion molecules, such as interleukin-8 (IL-8) and intercellular adhesion
      molecule-1 (ICAM-1), which are involved in the neutrophil infiltration and tissue
      damage in the inflamed colon. Notably, glucosamine, a naturally-occurring amino
      monosaccharide, has been shown to exhibit an anti-inflammatory action by
      inhibiting neutrophil functions. In the present study, to evaluate the anti
      inflammatory action of glucosamine on intestinal epithelial cells, we examined
      the effects of glucosamine on the activation of a human colonic epithelial cell
      line HT-29. The results revealed that glucosamine suppressed the IL-8 production
      and ICAM-1 expression by TNF-alpha-activated HT-29 cells. Furthermore,
      glucosamine inhibited the TNF-alpha-induced phosphorylation of p38MAPK and NF
      kappaB p65, and the nuclear translocation of NF-kappaB in the cells. Thus,
      glucosamine demonstrates inhibitory actions on the inflammatory and signaling
      molecules (IL-8, ICAM-1, p38MAPK and NF-kappaB) in intestinal epithelial cells.
      However, glucosamine did not essentially affect the binding of TNF-alpha to its
      receptor on HT-29 cells. Together, these observations suggest that glucosamine
      may have the potential to exhibit an anti-inflammatory action on intestinal
      epithelial cells, by possibly interfering with the activation signaling
      downstream of the ligand/receptor binding.

PMID- 18636176
TI  - Cytotoxicity and stress gene microarray analysis in cadmium-exposed CRL-1439
      normal rat liver cells.
AB  - Cadmium is a biologically non-essential divalent hazardous metal. Previous
      studies demonstrated that cadmium toxic effect was caused by reactive oxygen
      species. Since gene expression is influenced by the presence of these reactive
      oxygen species, the association between metal intoxication and gene expression
      has recently become a major focus of research. We examined the effect of cadmium
      chloride on cell viability at 4, 8 and 24 h. Our results indicate that cadmium
      chloride did not alter cell viability at 4 or 8 h, but decreased the viability in
      a dose-dependent manner (p>0.01) at 24 h. Using DNA microarray, we studied the
      profile of stress gene expression in rat primary hepatocytes treated with cadmium
      for different time periods using a 100 microM cadmium chloride concentration.
      Microarray analysis indicated that cadmium treatment caused different patterns of
      gene expression profiles at each time point of incubation. Of the 207 stress
      genes on the microarray, only 32 genes were regulated. Since microarrays were
      hybridized by radioactive cDNA which was less sensitive than fluorescent-labeled
      cDNA, an experimental/control ratio >1.3 or <0.7 (30% increase or decrease) was
      taken as significant up- or down-regulation. Exposure of cells to cadmium for 4 h
      resulted in the expression of three up-regulated genes and six down-regulated
      genes. Longer exposure to cadmium for 8 h resulted in an increase in up-regulated
      genes to six and down-regulated genes to 14. After 24 h of cadmium exposure, 15
      genes were down-regulated and six genes were up-regulated. Our findings suggest
      that the cells maintained complete viability up to 8 h with cadmium due to
      expression of various heat shock proteins and stress response proteins like heme
      oxygenase. Longer exposure periods, due to the down-regulation of the basic cell
      function proteins and cell-cycle regulating proteins, led to toxicity in cells
      and eventually to cell death.

PMID- 18636177
TI  - Combination of beta-cryptoxanthin and zinc has potent effects on apoptotic cell
      death and suppression of bone resorption-related gene expression in osteoclastic
      cells.
AB  - We investigated whether the effect of beta-cryptoxanthin (CRP) on osteoclastic
      cells formed in the mouse marrow culture system in vitro is enhanced by culture
      with zinc. Bone marrow cells were isolated from mice. The macrophage colony
      stimulating factor (M-CSF)-dependent bone marrow macrophages were cultured in the
      presence of M-CSF (10 ng/ml) and receptor activator of nuclear factor-kappaB (NF
      kappaB) ligand (RANKL; 50 ng/ml) for 96 h. The osteoclastic cells formed were
      further cultured for 24 or 72 h in a medium containing either vehicle, CRP, zinc
      sulfate (zinc), or CRP plus zinc with or without M-CSF (10 ng/ml) and RANKL (50
      ng/ml). The number of osteoclastic cells was significantly decreased after
      culture with the combination of CRP (10(-7) M) and zinc (10(-5) M) in the
      presence or absence of M-CSF and RANKL for 24 or 72 h as compared with the value
      for CRP or zinc alone. Agarose gel electrophoresis showed the presence of low
      molecular weight deoxyribonucleic acid (DNA) fragments of adherent cells cultured
      with CRP (10(-7) M) plus zinc (10(-5) M) for 24 or 72 h in the presence of M-CSF
      and RANKL, indicating that the combination of the two chemicals induces apoptotic
      cell death. CRP plus zinc-induced decrease in osteoclastic cells was
      significantly inhibited in the presence of caspase-3 inhibitor (10(-8) or 10(-7)
      M). Culture with CRP (10(-7) M) plus zinc ((10(-5) M) for 24 or 72 h caused a
      significant increase in caspase-3 mRNA expression in the presence or absence of M
      CSF and RANKL as compared with the value for each chemical alone. CRP plus zinc
      induced increase in caspase-3 mRNA expression was completely inhibited in the
      presence of cycloheximide (10(-7) M), an inhibitor of protein synthesis, or 5,6
      dichloro-1-beta-D-ribofuranosylbenzimidazole (DBR; 10(-6) M), an inhibitor of
      transcription activity. The mRNA expression of tartrate-resistant acid
      phosphatase (TRACP) and cathepsin K was significantly decreased after culture
      with CRP plus zinc in the presence or absence of M-CSF and RANKL for 72 h as
      compared with CRP or zinc alone. Nuclear factor of activated T cells c1 (NFATc1)
      mRNA expression was significantly decreased after culture with CRP plus zinc in
      the presence or absence of M-CSF and RANKL for 72 h as compared with each
      chemical alone, while NF-kappaB mRNA expression was not significantly changed.
      This study demonstrated that the combination of CRP and zinc has potent
      suppressive effects on osteoclastic cells in vitro.

PMID- 18636178
TI  - Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid
      through inhibition of EGFR/ERK in cultured human skin keratinocytes.
AB  - The most common adverse effects that are related to all-trans retinoic acid
      (atRA) treatment are irritation and dryness of the skin. atRA therapy is reported
      to impair barrier function as achieved by trans-epidermal water loss (TEWL).
      Treatment with nicotinamide prior to initiation of atRA therapy provides
      additional barrier protection and thus reduces susceptibility of retinoic acid.
      Our previous studies showed that atRA upregulates aquaporin 3 (AQP3) in cultured
      human skin keratinocytes and fibroblasts. Others have demonstrated that in atopic
      dermatitis, overexpression of AQP3 is linked to elevated TEWL and that
      nicotinamide treatment reduces skin TEWL. In this study, we observed that while
      atRA upregulates AQP3 expression in cultured human skin keratinocytes (HaCaT
      cells), nicotinamide attenuates the effect of atRA in a concentration-dependent
      manner. atRA treatment induces EGFR and ERK activation. PD153035, an EGFR
      inhibitor, and U0126, an ERK inhibitor, inhibit atRA-induced upregulation of
      AQP3. Nicotinamide also inhibits atRA-induced activation of EGFR/ERK signal
      transduction and decreases water permeability by downregulating AQP3 expression.
      Collectively, our results indicate that the effect of atRA on AQP3 expression is
      at least partly mediated by EGFR/ERK signaling in cultured human skin
      keratinocytes. Nicotinamide attenuates atRA-induced AQP3 expression through
      inhibition of EGFR/ERK signal transduction and eventually decreases water
      permeability and water loss. Our study provides insights into the molecular
      mechanism through which nicotinamide reverses the side effects of dryness in
      human skin after treatment with atRA.

PMID- 18636179
TI  - Rhodamine 123 efflux in human subpopulations of hematopoietic stem cells:
      comparison between bone marrow, umbilical cord blood and mobilized peripheral
      blood CD34+ cells.
AB  - Hematopoietic stem cells (HSC) can be identified by the expression of the CD34
      molecule. CD34+ cells are found in bone marrow (BM), umbilical cord blood (UCB)
      and in mobilized peripheral blood (PB). CD34+ cells express P-glycoprotein (Pgp),
      a product of the multidrug resistance (MDR) gene. Pgp activity can be measured by
      the efflux of the dye Rhodamine 123 (Rho 123) and can be blocked by verapamil.
      Transport activity in HSC suggests that Pgp could have a functional role in stem
      cell differentiation. This study compared the number of CD34+ cells with Pgp
      activity measured by efflux of Rho 123 in the hematopoietic population obtained
      from different sources. Samples were analysed for their content of CD34+ cells,
      and BM had a significantly higher amount of CD34+ cells compared to UCB,
      mobilized PB and normal PB. When the frequency of Rholow cells was studied among
      the CD34+ population, an enrichment of cells with Pgp activity was observed. The
      frequency in BM was significantly lower than that in UCB and mobilized PB. The
      low retention of Rho 123 could be modified by verapamil, indicating that the
      measurements reflected dye efflux due to Pgp activity. Although UCB and mobilized
      PB had a lower number of CD34+ cells compared to BM, the total number of CD34+
      cells with Pgp activity was similar in the three tissues. The different profiles
      may indicate the existence of subpopulations of stem cells or different stages of
      cellular differentiation detected by the extrusion of the dye Rho 123.

PMID- 18636180
TI  - Stimulatory effect of Shoyu polysaccharides from soy sauce on the intestinal
      immune system.
AB  - Soy sauce (Shoyu) is a traditional Japanese fermented seasoning and is available
      worldwide. We investigated the effect of Shoyu polysaccharides (SPS) prepared
      from soy sauce on the intestinal immune system of mice. SPS enhanced the
      production of immunoglobulin A (IgA) from Peyer's patch cells in vitro, and its
      oral administration to 7-week-old male BALB/c mice for 2 weeks at a dose of 1.5
      mg per day significantly (p<0.01) increased the concentration of IgA in the
      intestine as compared to control mice. Furthermore, experiments on the intestinal
      transport of SPS in vitro using the human intestinal epithelial cell line Caco-2
      confirmed the permeation of uronic acid to be time-dependent. In conclusion, SPS
      of soy sauce enhanced the production of IgA in vitro and in vivo, and the
      digested SPS might cross the enterocytic monolayer. Thus, soy sauce is a
      potentially promising food for enhancing host defenses.

PMID- 18636181
TI  - Association study for single nucleotide polymorphisms in the CYP17A1 gene and
      polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) are characterized by excess androgen
      secretion and anovulatory infertility as a cause of follicular maturation arrest,
      and they are also associated with insulin resistance and obesity. Recently, it
      was suggested that one of the etiologies for PCOS is an abnormality of steroid
      hormones, and excessive secretion of androgen. The endoplasmic reticular
      cytochrome P450, 17alpha-hydroxylase (CYP17A), plays a key role in the mechanism
      of steroid hormones such as adrenal and gonadal steroid biosynthesis. Therefore,
      we studied the association between single nucleotide polymorphisms (SNPs) of the
      A1 allelic variant of the CYP17 gene and PCOS in a Korean population. The study
      recruited 134 Korean women with PCOS and 100 healthy women as controls. Using the
      HapAnalyzer, the genotype of the CYP17A1 polymorphism in PCOS and control
      patients were analyzed. We considered a p-value lower than 0.05 to be
      statistically significant. After genotypic analysis, we found seven SNPs of the
      CYP17A1 gene in a large population of subjects. The frequency of seven SNPs had
      no significant association with PCOS. However, one haplotype (ht3) had a p-value
      of p=0.001, suggesting that it may be associated with the pathogenesis of PCOS in
      a Korean population.

PMID- 18636182
TI  - Correlation between liver and plasma fatty acid profile of phospholipids and
      triglycerides in rats.
AB  - Considering the changes in the fatty acid profile of liver lipids related to age,
      gender and nutritional status or occurring in pathological situations, this study
      aimed at investigating whether such changes could be judged from measurements
      conducted in plasma lipids. The fatty acid profile of both liver and plasma
      phospholipids and triglycerides was measured in 16 control animals and 26 rats
      depleted in long-chain polyunsaturated (n-3) fatty acids. Within each group of
      rats, significant correlations prevailed between the percentage of each fatty
      acid in liver versus plasma phospholipids or triglycerides. However, the
      plasma/liver ratio for the relative content of C20:5(n-3), C22:5(n-3) and C22:6(n
      3) in triglycerides displayed abnormally high values in 2 control animals. The
      fatty acid profile of liver phospholipids and triglycerides can, as a rule, be
      judged from measurements made in the corresponding plasma lipids. For instance,
      measurements in plasma phospholipids could help to identify subjects deficient in
      (n-3) fatty acids and to assess the dietary correction of this defect.

PMID- 18636183
TI  - Pyrogallol inhibits the growth of gastric cancer SNU-484 cells via induction of
      apoptosis.
AB  - Pyrogallol (PG) is a polyphenol compound and is known to be an O2*- generator. We
      evaluated the effects of PG on the growth of human gastric cancer SNU-484 cells
      in relation to the cell cycle and apoptosis. Dose-dependent inhibition of cell
      growth was observed in SNU-484 cells with an IC50 of approximately 50 microM
      following treatment with PG for 72 h. DNA flow cytometric analysis indicated that
      treatment with PG generally did not induce the specific cell cycle phase arrest.
      Treatment with 50 microM PG induced apoptosis approximately 20%, as evidenced by
      sub-G1 cells and annexin V-staining cells. Treatment with PG also induced the
      loss of mitochondrial membrane potential (Delta psi m) in SNU-484 cells. The
      intracellular reactive oxygen species (ROS) levels including O2*- were
      significantly increased in PG-treated cells. Furthermore, the depletion of the
      intracellular glutathione (GSH) content was observed in cells treated with 50 or
      80 microM PG. In conclusion, PG inhibited the growth of human gastric cancer SNU
      484 cells by inducing cell cycle arrest as well as triggering apoptosis. The
      changes in ROS and GSH by PG were closely related to apoptosis in SNU-484 cells.

PMID- 18636184
TI  - Pathological complete response induced by the combination therapy of S-1 and 24-h
      infusion of cisplatin in two cases initially diagnosed as inoperable advanced
      gastric cancer.
AB  - We report on two patients, successfully treated by the combination therapy of S-1
      and 24-h infusion of cisplatin (CDDP), who were initially diagnosed with
      unresectable stage 4 advanced gastric cancer. Each patient had a very good
      clinical response and underwent curative gastrectomy after completion of 14 and
      10 courses of S-1/CDDP chemotherapy, respectively. A microscopically detailed
      examination of surgically obtained specimens showed the complete disappearance of
      malignant cells in the two cases. S-1/CDDP combination therapy can, therefore, be
      highly active in incurable advanced gastric carcinoma.

PMID- 18636185
TI  - Expression of copper-transporting P-type adenosine triphosphatase (ATP7B)
      correlates with cisplatin resistance in human non-small cell lung cancer
      xenografts.
AB  - Copper-transporting P-type adenosine triphosphatase (ATP7B) is reportedly
      associated with platinum drug resistance in various solid carcinomas. However,
      the impact of ATP7B on platinum drug resistance in non-small cell lung cancer
      (NSCLC) remains unknown. We investigated ATP7B expression in nine human NSCLC
      xenografts using real-time polymerase chain reaction (PCR) and
      immunohistochemistry, and examined the relationship between the expression level
      of ATP7B and in vivo cisplatin (CDDP) sensitivity. ATP7B mRNA expression was
      significantly correlated with in vivo cisplatin sensitivity [coefficient of
      determination (R(2))=0.949, p=0.005]. ATP7B protein was detected in the nine
      xenografts. The ATP7B protein expression level was comparable to that of ATP7B
      mRNA. ATP7B mRNA and protein expression levels in the CDDP-resistant xenografts
      were significantly higher than those in the CDDP-sensitive xenografts (p=0.0389
      and p=0.0357, respectively, Mann-Whitney U test). These results suggest that
      ATP7B is a CDDP-resistance marker in human NSCLC xenografts in vivo.

PMID- 18636186
TI  - Combinations of apoptosis and cell-cycle control biomarkers predict the outcome
      of human melanoma.
AB  - The deregulation of apoptosis is characteristic of human carcinogenesis.
      Survivin, an inhibitor of apoptosis, p53 and p16, two tumour suppressor proteins
      involved in cell cycle control, play a central role in apoptosis. The aim of this
      study was to investigate, in primary cutaneous melanoma from 68 patients, the
      expression of survivin with respect to p53 or p16; the association of these
      proteins, alone or in combination with clinicopathological features; and, most
      importantly, to elucidate the role of these markers in predicting survival. The
      level of survivin expression was significantly higher in the p53 positive group
      of melanomas compared with the p53 negative one, suggesting a cooperative effect
      in favouring the progression of melanoma, while no correlation was found between
      survivin and p16. Moreover, the altered expression of nuclear survivin, p53 and
      p16 were all associated with poor survival, as demonstrated by univariate
      analysis. However, these biomarkers have been shown to have superior predictive
      value when studied in combination (P<0.0001) rather than alone, while the risk of
      mortality grew progressively with increasing the number of altered biomarkers.
      These data suggest that the assessment of the combined marker status and number
      of altered markers in patients with melanoma provides important additional
      prognostic information that may help in patient selection for adjuvant therapies.

PMID- 18636187
TI  - Ribonucleotide reductase subunit M1 is a possible chemoresistance marker to
      gemcitabine in biliary tract carcinoma.
AB  - Biliary tract carcinoma is a relatively rare tumor with a poor prognosis.
      Surgical resection is the only potential cure. However, the efficacy of
      chemotherapeutic agents is disappointing in advanced or recurrent cases.
      Gemcitabine (GEM) appears to be one of the most promising chemotherapeutic agents
      in biliary tract carcinoma, and ribonucleotide reductase subunit M1 (RRM1) plays
      an important role in GEM resistance. The aim of this study was to evaluate the
      correlation between the expression of RRM1 and the response to GEM in biliary
      tract carcinoma in vitro and in vivo. The drug sensitivity to GEM was assessed by
      MTT assay. The expression of RRM1 was evaluated by quantitative RT-PCR, a Western
      blot analysis and immunohistochemistry. RNAi assay was used to investigate the
      down-regulation of the expression of RRM1. After the RRM1-specific RNAi
      transfection, a cell growth assay was performed to evaluate the drug sensitivity
      to GEM, and flow cytometry and TUNEL assay were performed to evaluate apoptosis.
      The results showed that in 6 biliary tract carcinoma cell lines, a tendency for a
      positive correlation between the expression of RRM1 and IC50 for GEM exists
      (R=0.620, p=0.19). The transfection of the RRM1-specific RNAi suppressed the
      expression level of RRM1 in a dose-dependent manner. After the transfection of
      RRM1-specific RNAi into G-415, the drug sensitivity to GEM markedly increased
      (p<0.001), and apoptosis was highly induced according to flow cytometry and the
      TUNEL assay. In an analysis of cancer tissue specimens obtained from the 12
      patients treated with GEM for biliary tract cancer, RRM1 immunostaining was
      strongly positive in all of the PD cases (3/3), while weakly positive in all of
      the PR cases except for one (4/5). In conclusion, RRM1 may be one of the key
      marker molecules for GEM chemotherapy that overcomes advanced and recurrent
      biliary tract carcinoma.

PMID- 18636188
TI  - Gene expression profiling of oral submucous fibrosis using oligonucleotide
      microarray.
AB  - Although oral submucous fibrosis (OSF) is the most common precancerous lesion of
      the oral cavity in Southeast Asia where the habit of betel quid (BQ) chewing is
      popular, its molecular biological properties are largely unknown. The aim of this
      study was to identify the genes responsible for its pathogenesis and malignant
      transformation using oligonucleotide microarray. The expression profiles of
      14,500 genes in human oral submucous fibrosis and normal control were analyzed
      using Affymetrix U133A 2.0 GeneChip arrays. The results revealed that 716 genes
      were upregulated and 149 genes were downregulated in OSF. Hierarchical clustering
      revealed that the gene expression profiles of normal and OSF were clearly
      distinct by these different expression genes. Gene Ontology (GO) and relevant
      bioinformatics tools identified a list of significant differentially expressed
      genes involved in immune response, inflammatory response and epithelial
      mesenchymal transition (EMT) induced by TGF-beta signaling pathway. Five EMT
      related genes including SFRP4, THBS1, MMP2, ZO-1, and CK18 were validated with RT
      PCR. Our data suggested that gene abnormalities in immune response, inflammatory
      response and EMT induced by TGF-beta might play an important role in the
      pathogenesis and malignant transformation of OSF.

PMID- 18636189
TI  - Telmisartan is a potent target for prevention and treatment in human prostate
      cancer.
AB  - Angiotensin II receptor blockers (ARBs) are widely used as hypertensive
      therapeutic agent. Recent studies have reported that ARBs have the potential to
      inhibit the growth of prostate cancer (PC) cells. Moreover, it was recently
      reported that Telmisartan (a kind of ARB) has peroxisome proliferator-activated
      receptor (PPAR)-gamma activation. We previously reported that PPAR-gamma ligand
      induces growth arrest of PC cells through apoptosis. In this study, we evaluated
      the effects of the Telmisartan and other ARBs on cell proliferation in several PC
      cell lines. We used normal prostate stromal cell (NPC), human hormone-refractory
      PC (PC3), androgen-independent PC (DU-145) and androgen-dependent PC (LNCaP) cell
      lines. Effects of Telmisartan and other ARBs (Candesartan, Valsartan, Irbesartan
      and Losartan) on PC cell growth were examined by MTT assay. Flow cytometry and
      Hoechst staining were used to determine whether or not ARBs induce apoptosis.
      Telmisartan caused marked inhibition of PC cells in concentration-dependent and
      time-dependent manner. PC cells with treatment of 100 microM Telmisartan induced
      early apoptosis and DNA fragmentation. However, NPC with treatment of 100 microM
      Telmisartan did not induce apoptosis or DNA fragmentation. Furthermore, other
      ARBs had no effect on cell proliferation in the PC cells and NPC. Telmisartan may
      mediate potent antiproliferative effects against PC cells through PPAR-gamma.
      Thus, Telmisartan is a potent target for prevention and treatment in PC.

PMID- 18636190
TI  - Expression analysis of the autosomal recessive primary microcephaly genes MCPH1
      (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated)
      in human malignant gliomas.
AB  - Patients with autosomal recessive primary microcephaly have a small but
      architecturally normal brain containing a reduced number of neurons.
      Microcephalin and ASPM are two of the genes causing this disease. Both are
      centrosomal proteins involved in cell cycle regulation. Whereas microcephalin is
      a component of the DNA damage response and a repressor of telomerase function,
      ASPM is required for the proper formation of a central mitotic spindle and
      ensures symmetric, proliferative divisions of neuro-epithelial cells. Both
      proteins are also involved in the regulation of tumor growth. Microcephalin
      expression is reduced in breast cancer cell lines and human tumors of the ovary
      and prostate. Reduction in microcephalin mRNA expression correlates with
      increased chromosomal instability. ASPM mRNA is overexpressed in transformed
      human cell lines and tumors, and its increased expression is positively
      associated with proliferation of glioblastoma cells. Glioblastomas are the most
      prevalent malignant brain tumors in adults, characterized by increased
      invasiveness, an aggressive local growth pattern and short survival periods of
      patients. In this study, we analysed the expression of microcephalin mRNA and
      ASPM mRNA and protein in a panel of 15 glioblastomas and 15 astrocytoma WHO grade
      II by semi-quantitative RT-PCR, Western blotting and immunohistochemistry.
      Whereas microcephalin expression did not seem to be altered during glioma
      development, there was a clear increase in ASPM mRNA and protein expression that
      corresponded with the WHO grade of the tumor. Our findings are significant as the
      expression of ASPM may be used as a marker for glioma malignancy and represents a
      potential therapeutic target.

PMID- 18636191
TI  - The role of tumor vascularisation in benign and malignant cardiovascular
      neoplasms: a comparison of cardiac myxoma and sarcomas of the pulmonary artery.
AB  - Neoangiogenesis is involved in the development and progression of malignant
      tumors. Vascular endothelial growth factor (VEGF) and its receptors have been
      designated a central part in this process. Since the significance of the
      assessment of angiogenesis in soft tissue tumors is still a matter of debate, we
      investigated the vascularisation of cardiac myxomas and compared it with
      pulmonary artery sarcomas (PAS). Angiogenesis in 18 PAS and 20 myxomas was
      assessed by morphometry. An immunohistochemical analysis of growth factors and
      their receptors, HIF-1alpha and tumor-associated macrophages (TAM) was performed.
      Results showed that microvessel density (MVD) in PAS was significantly higher at
      the border of necrosis versus the areas without necrosis but no difference was
      observed between PAS and myxomas. Vascular surface area (VSA) and intervascular
      distances showed a higher vascularisation at the border of necrosis compared to
      myxomas, which was not significant. VEGF expression was higher in PAS compared to
      myxomas and was prominent at the sites of necrosis. HIF-1alpha expression was
      marked at the border of necrosis in PAS but was absent in myxomas. Infiltration
      of the macrophages was significantly higher in myxomas compared to the sarcomas.
      VEGFR-2 expression was detected in a subset of tumor cells and in blood vessels
      mainly at the tumor periphery, whereas VEGFR-1 was weakly expressed in the tumors
      but prominent in the macrophages in cardiac myxomas. PDGF receptors and their
      ligands are strongly present in myxomas and to a lesser extent in the sarcomas.
      In conclusion, benign and malignant cardiovascular tumors with a different
      pathophysiology develop a comparable vascularisation. Hypoxia appears to be the
      strongest inducer of neoangiogenesis in the sarcomas. The expression of receptor
      tyrosine kinases of the VEGF family provides a basis for an adjuvant therapy.

PMID- 18636192
TI  - Diallyl sulfide inhibits PhIP-induced cell death via the inhibition of DNA strand
      breaks in normal human breast epithelial cells.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is associated with mammary
      carcinomas in animals and humans. PhIP is metabolized by CYP 1A1/1A2 and
      cytochrome b5 reductase, producing free radicals causing DNA strand breaks.
      Diallyl sulfide (DAS) prevents cancer in animals. We hypothesized that DAS will
      attenuate PhIP-induced DNA strand breaks and cell death. To test this hypothesis,
      we treated MCF-10A cells with PhIP, DAS and PhIP/DAS for 24, 48 and 72 h. DAS
      inhibited the PhIP-induced DNA strand breaks by 22% after 48 h and the strand
      breaks were completely inhibited at 72 h. PhIP reduced cell viability at each
      time point. However, DAS only attenuated this reduction in cell viability by 56%
      at 72 h. N-OH PhIP inhibited cell viability by 26% at 72 h. DAS completely
      attenuated this reduction in cell viability and may prevent PhIP-induced breast
      cancer via alterations in DNA damage and cell viability.

PMID- 18636193
TI  - S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3.
AB  - S100P is a member of the S100 family of calcium-binding proteins. Our previous
      studies have demonstrated its significant downregulation in oxaliplatin-resistant
      colon cancer cell line. The present study investigated whether it plays a role in
      the regulation of chemosensitivity to anticancer drugs using human ovarian cancer
      cell line OVCAR3. We firstly overexpressed S100P in the OVCAR3 cell line, and
      evaluated the expression level of S100P by semiquantitative RT-PCR, Western
      blotting and immunofluorescence assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium (MTT) assay indicated that overexpression of S100P sensitized
      OVCAR3 cells for chemotherapeutic drugs (paclitaxel, oxaliplatin, 5-fluorouracil,
      etoposide and epirubicin) induced cytotoxicity more than vector-only controls.
      Further studies showed that downregulation of S100P by RNA interference in OVCAR3
      cells led to a significant increase of resistance to each of these anticancer
      drugs. Taken together, our results suggest that S100P plays an important role in
      regulation of chemosensitivity to anticancer drugs in ovarian cancer cells. Using
      S100P as a molecular biomarker may increase our ability to predict tumor drug
      response in ovarian cancer.

PMID- 18636194
TI  - Human papillomavirus type 16 and 18 infection is associated with lung cancer
      patients from the central part of China.
AB  - Infection with specific high-risk human papillomavirus (HPV) types 16 and 18 have
      been strongly associated with the genesis of various neoplasms in humans, though
      such study in lung cancer is limited and the results are controversial. In the
      present study, we collected and explored 313 fresh lung tumor specimens for the
      presence of HPV with polymerase chain reaction and non-isotopic in situ
      hybridization. We found that 44.1% of (138/313) non-small cell lung carcinoma
      (NSCLC) samples were positive for HPV detection, while 4.2% (4/96) of lung benign
      controls were positive for HPV 16 and 18 DNA. HPV infection was significant
      between lung squamous cell carcinoma and adenocarcinoma as well as smoking and
      non-smoking patients. In HPV-positive lung cancer tissues, abnormal p53 protein
      accumulation was seen in 97 of the 138 carcinomas (70.3%) and expression of pRb
      in 54 of the 138 carcinomas (39.1%). There was an obvious relationship between
      the presence of papilloma viral DNA and abnormal p53 protein accumulation and pRb
      depletion. Cell proliferation and apoptosis were correlated with HPV infection in
      NSCLC samples. Our data confirm the high prevalence of HPV in lung carcinomas in
      the central part of China and suggest the possible mechanism of the carcinogenic
      role of HPV in these carcinomas.

PMID- 18636195
TI  - Transfection of the DAAO gene and subsequent induction of cytotoxic oxidative
      stress by D-alanine in 9L cells.
AB  - D-amino acid oxidase (DAAO) can catalyze the dehydrogenation of D-amino acids,
      such as D-alanine, to the corresponding amino acids and is then reoxidized by
      molecular oxygen to yield hydrogen peroxide, a reactive oxygen species, which
      reacts with DNA, lipids and protein, inducing cell death. This study investigated
      whether rat glioma 9L cells infected with the recombinant retrovirus containing
      the DAAO cDNA fragment can be induced in order to undergo cytotoxic oxidative
      stress by D-alanine. The recombinant retroviral vector, plzrus-DAAO-FLAG-GFP (pl
      Dfg), was constructed and used to transfect packaged phoenix cells. The
      supernatant containing recombinant retroviral particles from the transfected
      phoenix cells was harvested and utilized to infect target 9L cells. The cytotoxic
      oxidative stress of infected 9L cells was induced by the DAAO substrate, D
      alanine. The plasmid pl-Dfg was successfully constructed. The high titer
      retroviral supernatant was obtained from the transfected phoenix cells. Infected
      9L cells were less viable after exposure to D-alanine compared to the control
      group. Anti-apoptotic proteins significantly inhibited cell death. The DAAO/D
      alanine system has a potential utility for gene therapy and may be an effective
      strategy for the treatment of brain cancer and other malignant tumors.

PMID- 18636196
TI  - Hedgehog-Patched pathway aberrations in a malignant triton tumor case study.
AB  - Transition from malignant schwannoma to malignant triton tumor is analyzed in a
      case report on a patient with recurring cancers and suspected familial
      predisposition. It is hypothesized that rhabdomyoblastic differentiation, which
      distinguishes triton from schwannoma, might be attributable to Hedgehog-Patched
      pathway malfunctioning. Loss of one Patched gene allele was found in the tissue
      of advanced triton, but the retained allele had no exon or promoter mutations.
      Protein levels at early cancer stages indicated possible Patched response to the
      pathway activation in the first occurrence of triton tumor. Later, in the
      recurring triton, Patched expression was several times lower than in the control
      tissue, suggesting that haploinsufficiency was aided by silencing of the
      remaining allele, although its promoter was not hypermethylated. These findings
      may justify further investigation of the Hedgehog-Patched pathway role in triton
      malignancies, especially because of the recent research on the therapeutical
      potential of the pathway.

PMID- 18636197
TI  - Significance of trans-hepatic arterial chemotherapy for advanced hepatocellular
      carcinoma with portal vein tumor thrombus.
AB  - Portal vein tumor thrombus (PVTT) is observed in a considerable number of
      hepatocellular carcinoma (HCC) cases. It is an exacerbating factor for patients
      afflicted with HCC. The sequelae of PVTT are considered to be a contraindication
      for the treatment of HCC in such patients. The survival of 10 HCC patients with
      PVTT treated with trans-hepatic arterial continuous injection chemotherapy was
      compared to 13 HCC patients with PVTT, who received best supportive care only, as
      a control to validate the efficacy of continuous trans-hepatic arterial injection
      chemotherapy using an implanted catheter for HCC with PVTT. There were no
      differences in the liver function and HCC stage between the two groups. The
      survival was significantly different between the two groups (P=0.01 by the log
      rank test). The median survival time was 106 days in the treatment patients,
      whereas it was 65 days in the control patients. Multivariate analyses showed the
      therapy to be the only predictor for survival (risk ratio 0.144, P=0.016). The
      therapy was strongly associated with the PVTT prognosis. In conclusion, the
      importance of trans-arterial chemotherapy was demonstrated even in advanced
      dysfunctional cirrhotic HCC patients with PVTT. It is therefore necessary to
      develop a basic protocol to treat HCC with PVTT.

PMID- 18636198
TI  - Clinicopathological significance of the gene expression of matrix
      metalloproteinase-7, insulin-like growth factor-1, insulin-like growth factor-2
      and insulin-like growth factor-1 receptor in patients with colorectal cancer:
      insulin-like growth factor-1 receptor gene expression is a useful predictor of
      liver metastasis from colorectal cancer.
AB  - Matrix metalloproteinase-7 (MMP-7), secreted by cancer cells, has been implicated
      classically in the basement membrane destruction associated with tumor cell
      invasion and metastasis. Epidemiological studies have established a correlation
      between high levels of circulating insulin-like growth factor-1 (IGF-1) and the
      relative risk of colorectal cancer, which is known to produce MMP-7. We examined
      the clinicopathological significance of the relative expression of MMP-7, IGF-1,
      IGF-2 and IGF-1 receptor genes in patients with colorectal cancer, especially
      with regard to metastasis. We studied surgical specimens of cancer tissue and
      adjacent normal mucosa obtained from 205 patients with untreated colorectal
      carcinoma. MMP-7, IGF-1, IGF-2, IGF-1R and beta-actin mRNA in cancer tissue and
      adjacent normal mucosa were measured by quantitative real-time reverse
      transcriptase polymerase chain reaction. MMP-7 and IGF-1R gene expression levels
      were higher in cancer tissue than in adjacent normal mucosa. In contrast, IGF-1
      gene expression was lower in cancer tissue than in adjacent normal mucosa. As for
      the relationship of gene expression to clinicopathological factors, IGF-1R
      expression correlated with venous invasion and liver metastasis. IGF-1R gene
      expression is thus considered a useful predictor of liver metastasis from
      colorectal cancer.

PMID- 18636199
TI  - Efficacy of doxorubicin thermosensitive liposomes (40 degrees C) and local
      hyperthermia on rat rhabdomyosarcoma.
AB  - The efficacy of novel thermosensitive liposomes (40 degrees C) containing
      doxorubicin (Dox-Lip) together with local hyperthermia (HT) was studied on solid
      growing rat rhabdomyosarcomas. Tumor response and systemic toxicity were
      evaluated by comparing to free doxorubicin (Free Dox) with or without
      hyperthermia. Tumors were heated with infrared-A-radiation and drugs were infused
      intravenously after preheating the tumors followed by a further 60 min of heating
      at 42.5 degrees C. Recorded temperatures at various locations in the tumors
      indicated that all intratumoral temperatures, especially at the back rim, were
      definitely >40 degrees C. After single doses, tumor growth was further inhibited
      by Dox-Lip+HT compared to Free Dox+HT or Free Dox alone. Repeated treatments with
      Dox-Lip+HT (2x2.5 mg/kg+HT/2 weeks) resulted in a statistically significant tumor
      growth delay and was associated with a much lower systemic toxicity. Uptake
      studies of drugs in blood, tumor and normal tissues showed that Dox-liposomes (40
      degrees C) are long circulating liposomes in the blood. However, the enhanced
      tumor response did not correlate with an increased uptake of Dox-Lip+HT in the
      tumor. The findings suggest that repeated applications of thermosensitive
      liposomal doxorubicin (40 degrees C) and local hyperthermia can control primary
      rat rhabdomyosarcomas while reducing the systemic toxicity of free doxorubicin.

PMID- 18636200
TI  - Antitumor effect of gefitinib on head and neck squamous cell carcinoma enhanced
      by trastuzumab.
AB  - The overexpression of EGFR and/or HER-2 is associated with tumor cell resistance
      to chemotherapy, radiotherapy, disease progression and poor prognosis in patients
      with a variety of malignant tumors. Treatment combining the EGFR-targeting drug,
      gefitinib (ZD1839, Iressa) with the HER-2-targeting drug, trastuzumab (Herceptin)
      has been reported to improve therapeutic efficacy in patients with breast cancer.
      The purpose of this study was to examine the antitumor effect of this combination
      on head and neck squamous cell carcinoma (HNSCC) in vitro. Cell proliferation was
      inhibited significantly in two cell lines. Although IC50 of gefitinib alone
      against some cell lines was not reached, it was achieved after being combined
      with trastuzumab. Furthermore, IC50 was lower for the combination than for
      gefitinib alone in several cell lines. These results suggest that the combination
      may improve efficacy against HNSCC.

PMID- 18636201
TI  - Combination treatment with arsenic trioxide and sulindac enhances apoptotic cell
      death in lung cancer cells via activation of oxidative stress and mitogen
      activated protein kinases.
AB  - Arsenic trioxide (As2O3) has been introduced to the treatment of acute
      promyelocytic leukemia (APL), and has also been shown to induce apoptosis in a
      variety of solid tumor cell lines, including non-small cell lung cancer. However,
      the prohibitively high concentration required for the induction of apoptotic cell
      death in many solid tumor cells is unacceptable for clinical utilization due to
      the excessive toxicity associated with this dose. Sulindac is known to enhance
      the cellular responsiveness of tumors toward chemotherapeutic drugs. Herein, we
      demonstrated that combination treatment with As2O3 and sulindac resulted in a
      synergistic augmentation of cytotoxicity in H157 lung cancer cells, which was
      revealed by apoptotic induction as demonstrated by an increase in the sub-G0/G1
      fraction. In addition, combination treatment with As2O3 and sulindac increased
      reactive oxygen species (ROS) and oxidative stress, as evidenced by the heme
      oxygenase-1 (HO-1) expression and mitogen-activated protein kinase (MAPK)
      phosphorylation. MAPK inhibitors blocked the induction of HO-1 by combination
      treatment. Inhibitors of p38 and JNK partially inhibited the augmented cell death
      whereas the ERK inhibitor showed poor inhibition. Combination treatment with
      As2O3 and sulindac induced oxidative DNA damage in a time-dependent fashion,
      which was evaluated by H2AX phosphorylation along with HO-1 induction.

PMID- 18636202
TI  - Vascular endothelial growth factor monitoring in advanced hepatocellular
      carcinoma patients treated with radiofrequency ablation plus octreotide: a single
      center experience.
AB  - Local therapies such as radiofrequency ablation (RFA) represent a valuable choice
      in limited hepatocellular carcinoma (HCC) and are increasingly used also in
      advanced tumors. Medical treatments generally gave frustrating results in
      advanced HCC especially if comorbidities exist. Several biologic non
      chemotherapeutic drugs are currently tested in HCC and, among them, octreotide
      was evaluated in single series of HCC patients reporting conflicting results. We
      have treated a series of 35 patients affected by advanced HCC (26 M and 9 F; age
      range: 55-85 years, median: 73 years) with RFA followed by octreotide to
      primarily evaluate the safety of combined treatment and to give preliminary
      evaluation on its activity. We have also evaluated serum VEGF changes during the
      study. Child A and Child B represented 60% and about 34% of the cases,
      respectively. Only two patients with Child C compensated cirrhosis were included
      in this study. All patients have multiple liver HCC nodules and one had bone
      metastases. Two complete responses, 3 partial responses and 23 disease
      stabilization for at least three months were obtained (overall response rate,
      14,2%; clinical benefit, 80%). Mean overall survival was 31.4 months. The
      combined treatment was well tolerated. Statistically significant correlation was
      found between serum VEGF and tumor progression. In conclusion, the combination of
      RFA and octreotide was active in advanced HCC, however, confirmation in a larger
      series is required.

PMID- 18636203
TI  - Key promoter elements involved in transcriptional activation of the cancer
      related gene coding for S100P calcium-binding protein.
AB  - S100P gene encodes a calcium-binding protein expressed in different tumor tissues
      and is functionally implicated in malignant phenotype. Despite consistent
      relationship to cancer, regulation of S100P gene expression has remained
      unexplored. Here we determined the transcription start and defined the S100P core
      promoter. Using a series of the promoter constructs analyzed by dual luciferase
      reporter assay, we identified SMAD, STAT/CREB and SP/KLF binding sites as
      critical cis-elements required for S100P expression in cancer cells. We also
      demonstrated in EMSA that these elements bind nuclear factors, and showed their
      functional significance by promoter deletion analysis. This study represents the
      first coherent contribution to understanding of factors and pathways responsible
      for S100P gene activation in cancer.

PMID- 18636204
TI  - Enhancement of sodium butyrate-induced cell death and apoptosis by X-irradiation
      in the human colorectal cancer cell line HCT 116.
AB  - In this study, we aimed at evaluating the possible enhancing effect exerted by
      the combined use of sodium butyrate (SB) and X-rays on eradicating the human
      colorectal cancer cell line HCT 116 containing wild-type p53. We assessed the
      effect of this combination on the molecular pathways leading to cell death. HCT
      116 cells were subjected to SB (1 mM) treatment followed by X-irradiation (5 Gy),
      and the effects on cell death, cell proliferation and cell cycle were examined.
      We also analyzed the apoptosis-indicating protein expression, mitochondrial
      membrane potential and intracellular superoxide formation. Treatment with SB
      alone significantly induced cell cycle arrest and apoptosis, whereas X
      irradiation showed no effect on cell death despite its ability to block cell
      proliferation. Growth arrest and cell death were enhanced in the combined
      treatment groups. A marked reduction in the growth rate of the combined-treatment
      group was observed compared to that of the single-treatment groups. The apoptotic
      mitochondrial pathway was significantly enhanced with the combined use of the two
      agents. It was observed to be involved in the increased expression levels of p53
      and p21, as well as in the release of cytochrome c and the alteration of the
      balance of anti- and pro-apoptotic Bcl-2 family proteins. Enhanced superoxide
      formation was also observed. However, the death receptor pathway was found to
      play no role in this phenomenon. These results suggest that X-irradiation
      promotes cell killing in synergy with SB treatment. Thus, the combined treatment
      led to a mutual potentiation of the killing effects of each agent.

PMID- 18636205
TI  - Analysis of the methylation status of genes up-regulated by the demethylating
      agent, 5-aza-2'-deoxycytidine, in esophageal squamous cell carcinoma.
AB  - To determine the clinical significance of gene promoter methylation in esophageal
      squamous cell carcinoma (ESCC), we examined the promoter methylation status of
      genes showing elevated expression, as determined by DNA microarray-based
      transcriptomic analysis, in three ESCC cell lines (TE-1, TE-2, TE-10) after 5-aza
      2'-deoxycytidine (DAC) treatment. We observed a high degree of DNA methylation
      within the promoter regions of three genes, namely cathepsin L2 (CTSL2), normal
      mucosa of esophagus specific 1 (NMES1), and fatty acid binding protein 5 (FABP5).
      Overexpression of NMES1 in ESCC cell lines increased cell motility. Down
      regulation of NMES1 might play an important role in the cell motility of ESCC or
      be a potent marker of malignancy.

PMID- 18636206
TI  - Rapid detection of the hypoxia-regulated CA-IX and NDRG1 gene expression in
      different glioblastoma cells in vitro.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a key regulator of tumor cell hypoxia. It
      regulates the expression of several genes related to oxygen homeostasis in
      response to hypoxic stress. Carbonic anhydrase IX (Ca-IX) has been found to be a
      stable marker of acute or chronic hypoxia. N-Myc down-regulated gene 1 (NDRG1)
      has been shown to possess more specific characteristics for clinical analysis and
      identification purposes. HIF-1 activates gene expression of the two genes and
      promotes tumor cell survival under hypoxic conditions. Herein, we modified a flow
      cytometry protocol to separate NDRG1- and CA-IX-negative and -positive cells in
      vitro to sort chronically hypoxic cells from glioblastoma tumors. The FITC-anti
      CA-IX fluorescence differed between positive and negative cells by a factor of 60
      160 in U373, U87-MG, U251 and GaMG, respectively. A clear effect of the O2
      concentration on CA-IX expression was visible in GaMG and U251 cell lines whereas
      U373 showed a less differentiated pattern. NDRG1 expression was present in U373,
      U251 and GaMG with the lowest expression rate in GaMG. It was stable over 48 h of
      reoxygenation after 24 h of extreme hypoxia (0.1% O2). During reoxygenation NDRG1
      was relatively stable in the four tumor cell lines with the lowest expression in
      GaMG. An oxygen- and time-dependent elevation of nuclear HIF-1alpha binding on
      HRE was displayed. FACS analysis of CA-IX and NDRG1 expression may be a new
      approach to determining the hypoxic state of tumor cells. However, an extensive
      analysis of other hypoxia-regulated genes in different tumors is required to
      identify additional markers for the detection of the oxygenation state in human
      tumors in order to tailor effective tumor-specific therapeutic strategies.

PMID- 18636207
TI  - Expression of TMEM87B interacting with the human papillomavirus type 18 E6
      oncogene in the Hela cDNA library by a yeast two-hybrid system.
AB  - The high-risk human papillomavirus oncoprotein 18 E6 (HPV18 E6) is associated
      with cervix cancer. This study was conducted in order to identify the
      transmembrane protein 87B (TMEM87B) as a novel binding protein interacting with
      the HPV18 E6 oncoprotein and to perform an initial bioinformatics analysis. The
      yeast strain AH109 was transformed with pGBKT7-HPV18 E6 and the yeast mating
      assay was utilized to identify the interaction between TMEM87B and HPV18 E6 in
      the human Hela cDNA library. TMEM87B mRNA was detected in Hela cells by using RT
      PCR. The TMEM87B gene structure, genomic localization, physical and chemical
      characteristics, subcellular localization and functional domain were predicted,
      as well as the systematic evolution analysis on similar proteins among several
      species. In the yeast two-hybrid assay, HPV18 E6 mRNA was expressed and there was
      no self-activation and toxicity in the AH109 strain. The special TMEM87B mRNA
      expression was detected in Hela cells and the blue clones were validated by the
      yeast mating assay. An efficient bioinformatics analysis fundamentally identified
      that TMEM87B is a secretary protein, containing many phosphorylation sites and
      functional motifs and possibly involved in signal transduction and
      transcriptional control in carcinogenesis. It was indicated that the yeast two
      hybrid system is efficient for screening interacting proteins. The novel gene
      TMEM87B may interact with HPV18 E6 and may be a potential oncogenesis target
      according to the bioinformatics analysis.

PMID- 18636208
TI  - High corn oil and high extra virgin olive oil diets have different effects on the
      expression of differentiation-related genes in experimental mammary tumors.
AB  - Dietary lipids can modify the clinical behavior and morphological features of
      experimental breast tumors. We previously demonstrated that a high corn oil diet
      has a tumor-enhancing effect in 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced
      rat mammary adenocarcinomas, whereas a high olive oil diet acts as a negative
      modulator of carcinogenesis. In this study, we investigated whether these high
      fat diets modulate the expression of genes related to differentiation. Rats were
      induced with DMBA and fed a low fat diet, a high corn oil diet, a high olive oil
      diet, or both high fat diets. The expression levels of the mammary
      differentiation biomarkers alpha-casein, beta-casein and transferrin and of beta
      actin and its transporter zipcode binding protein 1 (ZBP1) were analyzed by
      Northern and/or Western blot in the mammary adenocarcinomas. The high fat diets
      did not induce changes in the expression of caseins, while transferrin expression
      was increased as a result of the high olive oil diet. beta-actin mRNA levels were
      higher in the high fat diet groups, though no changes in the protein levels were
      observed. The expression of ZBP1, a protein reported as having a role in
      carcinogenesis, was significantly increased by the high corn oil diet. These
      results suggest that in this model caseins are not good biomarkers of the changes
      in tumor morphological differentiation conferred by the high fat diets. The
      modulation of transferrin and ZBP1 expression by the high olive oil and the high
      corn oil diets could be one of the mechanisms by which such diets have a
      different influence on mammary carcinogenesis.

PMID- 18636209
TI  - mda-7/IL-24 induces apoptosis in human HepG2 hepatoma cells by endoplasmic
      reticulum stress.
AB  - mda-7/IL-24 shows tumor-suppressor activity in a broad spectrum of human cancer
      cells. However, the molecular mechanism by which mda-7/IL-24 induces apoptosis is
      not well understood and most likely involves different pathways depending on the
      tumor. We examined the apoptotic effect of the adenovirus-mediated mda-7/IL-24
      (Ad.mda-7) on human HepG2 hepatoma cells. We found that blocking the endoplasmic
      reticulum (ER) stress inhibited apoptosis induced by Ad.mda-7 and down-regulated
      the expression of caspase-12, Bax and caspase-3. The treatment of subcutaneous
      tumor xenografts of HepG2 cells with Ad.mda-7 inhibited tumor growth and
      angiogenesis. As in the in vitro studies, we found that blocking ER stress
      prevented Ad.mda-7 from inducing apoptosis in liver cancer cells in vivo. Our
      studies suggest that Ad.mda-7 induces apoptosis of HepG2 cells mainly through
      activation of the ER stress pathway.

PMID- 18636210
TI  - Immunotherapy with irradiated autologous leukemic cells in patients with B-CLL in
      early stages.
AB  - In this study 10(7) peripheral blood mononuclear cells including on average
      78.56% CD19+/CD5+ lymphocytes were irradiated, and then administered
      intradermally as an anti-cancer vaccine to seventeen patients with B-cell chronic
      lymphocytic leukemia (B-CLL) at early stages (twelve injections, four at a weekly
      interval followed by eight vaccines given every two weeks). In eight out of
      seventeen patients, in the first two injections, irradiated leukemic cells were
      mixed with bacillus Calmette-Guerin (BCG) to improve the efficacy of therapy by
      additional induction of innate immunity. A hematological improvement (as defined
      by a >25% reduction of leukocyte count) to autologous leukemic cell vaccines was
      observed in 5/17 patients, stabilisation of disease in 5/17 patients and in 7/17
      patients there was no response to immunotherapy. In seven patients significant
      increase of the lymphocyte doubling time was noted (p=0.02). There was no impact
      of BCG for immune responses or clinical outcome of vaccinated patients, but there
      was a significant increase of the absolute counts of CD3+ as well as of CD3+/CD4+
      and CD3+/CD8+ T cells during the vaccination period. We observed a significant
      improvement of the phagocytic function of autologous dendritic cells generated
      from peripheral blood monocytes obtained from patients with B-CLL after the end
      of immunotherapy (p=0.006). An association between the clinical outcome and the
      percentage of leukemic cells positive for expression of ZAP-70 and CD38 was
      noted. In conclusion, our results demonstrated the feasibility and safety of
      autologous irradiated leukemic cell immunotherapy in patients with B-CLL. As we
      noted immunological, and to some extent, clinical responses, this approach merits
      further investigation, including the use of adjuvants other than BCG.

PMID- 18636211
TI  - Number of negative points: a novel method for predicting radiosensitivity in head
      and neck tumor cell lines.
AB  - The present study was aimed at establishing a method that combines multiple
      factors of protein and genetic changes that enables prediction of
      radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines.
      In nine HNSCC cell lines, the quantity of protein expression and the type of
      genetic alterations were translated into a point system, called the Number of
      Negative Points. The expression of 14 proteins involved in growth control and/or
      apoptosis was quantified using a densitometric assessment of Western blots. The
      blots were adjusted to actin and standardised to normal oral keratinocytes
      classifying them into four groups depending on the amount of protein expressed (0
      3 points). Mutations of the p53 gene were classified into three groups and each
      mutation was given one point. Since the cell lines each had a known intrinsic
      radiosensitivity, a multivariate statistical calculation could then be performed
      to select for the combination of factors having the strongest correlation to
      radiosensitivity. The strongest correlation of the investigated factors was the
      combination of epidermal growth factor receptor, survivin and splice
      site/missense p53 mutations (R=0.990 and P<0.0001). No single factor had a
      significant correlation to the intrinsic radiosensitivity. Since a significant
      correlation to the intrinsic radiosensitivity was achieved only when two or more
      factors were combined, we conclude that a method such as the Number of Negative
      Points is necessary for prediction of treatment response. We present a novel
      method to combine factors which enables the prediction of radiosensitivity of
      HNSCC cell lines.

PMID- 18636212
TI  - Outcome of relapses of nephroblastoma in patients registered in the SIOP/GPOH
      trials and studies.
AB  - We registered 170 relapses in 1392 children with nephroblastoma in the SIOP/GPOH
      trials. The study aimed to evaluate prognostic factors for outcome in relapsed
      patients. Age, gender, initial stage, metastatic disease, local stage, histology,
      time to relapse and tumour volume were analysed for their prognostic relevance.
      Overall survival after relapse was 48% (median follow-up 5 years). Relapses were
      local in 28%, metastatic in 57% and combined in 15%. The median age of the cohort
      was 4.5 years whereas patients in complete continuous remission were
      significantly younger (3.1 years, p=0.001). Patients with initial stage I and II
      showed a significantly better prognosis than children with stage III (57 vs. 31%,
      p=0.008). Patients with high-risk tumours had a much poorer prognosis than those
      with intermediate and low-risk tumours (58 vs. 31%, p=0.003). Children with
      recurrence within 6 months after diagnosis had a poorer outcome than children
      relapsing later on (54 vs. 22%, p=0.0001). The tumour volume initially and after
      preoperative chemotherapy did not have any influence on outcome. Patients with
      isolated distant metastasis had a significantly better outcome than those with
      local and combined relapses (p=0.001). In conclusion, factors for poor prognosis
      after relapse are early relapse, local stage III, high-risk histology and
      combined relapse.

PMID- 18636213
TI  - Activation of the hTERT expression in squamous cell cervical carcinoma is not
      associated with gene amplification.
AB  - The hTERT gene encodes the telomerase catalytic subunit that plays a key role in
      cancer cell immortalization. Earlier, hTERT amplification was detected in
      squamous cell cervical carcinomas (SCC), however possible relations between
      elevated hTERT mRNA level and gene amplification was not studied. Here, we
      compared the hTERT expression and copy number in the same tumors by quantitative
      real-time PCR. The hTERT DNA copy number was virtually unchanged in all 33
      studied tumors, when compared to normal tissues. This result was confirmed using
      two reference genes beta-actin and beta-D-glucuronidase. Nevertheless, the
      activation of hTERT expression was found in 80% of cases (37/46, p<0.001). There
      was no correlation between the degree of mRNA increase and the tumor size and/or
      presence of metastases. No hTERT gene expression was observed in 20% of cases
      (9/46), while the control GADPH expression was unchanged. The detected elevation
      of the hTERT mRNA level was found using primers specific to functionally active
      full-length isoform of mRNA. Similar results were obtained with SCC cell lines
      carrying human papilloma virus (HPV) genomes. We conclude that frequent
      activation of hTERT expression in SCC is not associated with gene amplification.

PMID- 18636214
TI  - Elevated concentrations of ethinylestradiol, 17beta-estradiol, and
      medroxyprogesterone have little effect on reproduction and survival of
      Ceriodaphnia dubia.
AB  - Wastewater effluent contains synthetic and natural hormones, often in complex
      mixtures, that may be associated with reproductive abnormalities in fish and
      other aquatic biota. We exposed the sentinel invertebrate Ceriodaphnia dubia to
      the natural estrogen 17beta-estradiol (E(2)), a synthetic estrogen,
      ethinylestradiol (EE(2)), and a synthetic progestin, medroxyprogesterone in a 7
      day test. These compounds had no significant effect on reproduction or survival
      even at 10(6) times the concentrations at which reproductive effects have been
      documented in several fish species. C. dubia is routinely used for screening the
      toxicity of wastewater effluent. However, in the standard chronic 7-day exposure
      the endpoints of survival and reproduction were insensitive to several synthetic
      and natural vertebrate hormones. The C. dubia 7-day chronic toxicity test is
      probably not a useful monitoring tool for vertebrate hormones and their
      pharmaceutical analogs unless other sensitive endpoints such as maturation rates,
      molt frequency, and offspring sex ratios are incorporated in a practical manner.

PMID- 18636216
TI  - Intervariability among serum intact parathyroid hormone assays: a need for
      standardization.

PMID- 18636217
TI  - Geographical variations in hip fracture risk for women: strong effects hidden in
      standardised ratios.
AB  - There was 75% variation in the trend in hip fracture incidence with age in women
      aged 50 to 85 in France. In southwest France, the women are at higher risk of hip
      fracture at younger ages. This finding should be taken into account when
      examining risk factors. INTRODUCTION: Few studies have analysed the geographical
      variations in the relationship between age and hip fracture incidence. Our goal
      was to assess these variations among women under 85 within the same country.
      METHODS: The study population included women aged 50 to 85 who were living in
      France in 2004. Hip fracture cases were identified in the French Diagnosis
      Related Groups (DRG)-like database using the diagnosis code for closed hip
      fractures and procedural codes for treatment. The Moran index and a spatial model
      using latitude and longitude were used to assess the geographical heterogeneities
      of cumulative incidence risk (CIR) and age effect. RESULTS: A total of 29,218 hip
      fracture cases were identified. A south-to-north CIR gradient ranging from 7 to
      16% was observed. The variation in the number of years until double hip fracture
      incidence was 75% (i.e. 1.49 to 2.57 years). In the south, and more markedly in
      southwest France, the women are at higher risk of hip fracture at a younger age.
      CONCLUSION: The risk of fracture may be different between women of the same age.
      This may be hidden in a comparison of standardised ratios. This finding should be
      considered when examining risk factors and implementing public health
      interventions.

PMID- 18636218
TI  - Recollapse of previous vertebral compression fracture after percutaneous
      vertebroplasty.
AB  - This study was undertaken to investigate the incidence rate, characteristics, and
      predisposing factors associated with recollapse of the same vertebrae after
      percutaneous vertebroplasty (PVP). Recollapse of the same vertebra after PVP is
      the one of the complications of the procedure, and the incidence rate in our
      study was 3.21%. The most important predisposing factor was pre-operative
      osteonecrosis. Recollapse was not related to trauma. INTRODUCTION: PVP using
      polymethylmethacrylate has become a popular treatment for osteoporotic vertebral
      compression fracture. Recollapse of the same vertebrae after PVP has rarely been
      reported. This study was undertaken to investigate the incidence,
      characteristics, and predisposing factors associated with recollapse of the same
      vertebrae after PVP. METHODS: Eleven patients (seven females and four males; mean
      age, 69.91 +/- 5.49 years), out of a total of 343 patients, developed recollapse
      of the same vertebra after PVP. The 11 patients who developed recollapse
      comprised the "recollapse group", while the remaining 332 patients comprised the
      "well-maintained group". RESULTS: Pre-operative magnetic resonance imaging
      revealed that the incidence of osteonecrosis was significantly higher in the
      recollapse group than the well-maintained group (p < 0.05). The degree of re
      expansion of the compressed vertebral body after PVP was significantly higher in
      the recollapse group than in the well-maintained group (p < 0.05). CONCLUSIONS:
      The most important predisposing factor for recollapse was pre-operative
      osteonecrosis. Recollapse was not related to trauma. Osteoporotic vertebral
      compression fracture with osteonecrosis or pseudoarthrosis has been regarded as a
      relative indication for PVP; however, the findings of this study suggest that
      this disease category may be a relative contraindication for PVP.

PMID- 18636220
TI  - Molecular phylogenetic analysis of Barley yellow mosaic virus.
AB  - Complete nucleotide sequences of three strains (I, III, and IV) of Barley yellow
      mosaic virus (BaYMV) isolated in Japan were determined. The length of the genome
      was the same among the three strains; RNA1 was 7,642 nt and RNA2 was 3,585 nt.
      The molecular phylogenetic analysis showed that strain I was most closely related
      to the Chinese isolate, and these two strains formed one cluster with European
      isolates. Strains II, III, and IV, and the Korean isolate formed another cluster.
      Amino acid sequences of each viral gene product were compared among strains. The
      sequences of the VPg protein showed less identity among almost strains (less than
      92%) than the sequences of other proteins (more than 93%). VPg is thought to be
      involved in interactions with host factors, especially initiation factor 4E
      (eIF4E) or eIF(iso)4E, and infection. Therefore, the relationship between amino
      acid substitutions and infection of host plants is analyzed.

PMID- 18636219
TI  - Intervention with cloudy apple juice results in altered biological activities of
      ileostomy samples collected from individual volunteers.
AB  - BACKGROUND: Apple juice is considered to be an important component of the healthy
      diet, with anticancer activities in colon cancer animal models and key
      ingredients have numerous chemoprotective activities in human colon cells in
      vitro. AIM OF THE STUDY: Since only little is known on comparable activities in
      the human colon in vivo, here a pilot study was performed to assess related
      mechanisms caused by ileostomy samples from volunteers that had consumed apple
      juice. METHODS: Ileostomy samples were collected after intervention (0-8 h) with
      cloudy apple juice (1 l). They were characterized analytically for major apple
      polyphenols and biologically in HT29 colon cells for their potential to cause
      genotoxic damage, protect from the genotoxic insult by hydrogen peroxide
      (H(2)O(2)) and modulate the expression of GSTT2, an enzyme related to
      antioxidative defence against different peroxides. RESULTS: The analytical
      determination of polyphenols in the ileostomy samples revealed that the majority
      of the compounds were recovered in the samples collected 2 h after intervention.
      The comparison of genotoxic effects of samples before intervention and 2 h after
      intervention revealed a considerable variation of genotoxic response, but there
      was a trend for reduced genotoxicity in three of eight persons (P) after
      intervention. Samples collected at 2 h protected HT29 cells from genotoxic damage
      by H(2)O(2) (for 4 of 8 persons), resulted in an increased GSTT2 expression (for
      2 of 6 persons) and of GSTT2 promotor activity (2 of 6 persons). CONCLUSIONS: The
      intervention with apple juice results in bioavailable concentrations of related
      polyphenols in the gut lumen, which could contribute to reduced genotoxicity,
      enhanced antigenotoxicity and favorable modulation of GSTT2 gene expression in
      some individuals. The pilot study for the first time used this combination of
      faecal biomarkers which in larger cohorts may either reveal overall significant
      alterations of chemoprotection or may be used to identify individuals which could
      particularly benefit from a personalized nutrition.

PMID- 18636221
TI  - Synthesis and bioactivity of chemotactic tetrapeptides: fMLF-OMe analogues
      incorporating spacer aminoacids at the lateral positions.
AB  - A small library of N-For and N-Boc tetrapeptidic analogues of the chemotactic
      tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe), obtained by incorporating three
      different spacer aminoacids (Gly, betaAla and Pro) between the native residues of
      Met and Leu (N-For- and N-Boc-Met-Xaa-Leu-Phe-OMe; Xaa2 series) and Leu and Phe
      (N-For- and N-Boc-Met-Leu-Xaa-Phe-OMe; Xaa3 series), have been synthesized and
      examined for their biological activity as agonists and antagonists. Chemotaxis,
      lysozyme release and superoxide anion production have been measured. All the N
      For analogues maintain good to moderate chemotactic activity with the betaAla3 15
      model reaching the maximum value. All the N-Boc tetrapeptides are efficient
      chemotactic antagonists. Conversely, with the exception of the moderate
      antagonistic activity exhibited by the N-Boc Xaa2 models against lysozyme
      release, all the other N-Boc analogues do not show significant activity against
      both superoxide anion and lysozyme release.

PMID- 18636222
TI  - Inguinal hernia and occurrence on the other side: a prospective analysis in Iran.
AB  - BACKGROUND: Indirect inguinal hernia (IH) is the most common type of hernia.
      Routine contralateral inguinal exploration, without clinical evidence of a hernia
      is still controversial especially in children. The purpose of our study was to
      determine incidence of contralateral IH. METHODS: This is a prospective study of
      301 patients during a one-year period. History of groin mass, positive findings,
      demonstrable hernia, or communicating hydrocele were our criteria for diagnosis.
      RESULTS: Our study includes 301 infants and children, 270 (89.7%) males and 31
      (10.3%) females with mean age of two years and 40.9% under six months. In the
      follow-up period, we found 33 new IH in our patients. 23 (12%) of 196 patients
      less than two years old underwent contralateral herniorrhaphy in the follow-up
      period (P = 0.02). Six patients of 30 premature children underwent contralateral
      herniorrhaphy (P = 0.03). CONCLUSION: The incidence of contralateral hernia is
      approximately 10% and in our study it is approximately 1.7%. There is a
      significant difference between the occurrence of contralateral hernia in preterm
      compared with term infants (P = 0.03). We think that the incidence is still too
      low to recommend routine contralateral exploration.

PMID- 18636223
TI  - Obturator hernia: a diagnostic challenge.
AB  - We describe a case of an 82-year-old lady with groin pain secondary to an
      obturator hernia. She was a diagnostic challenge, and 6 years passed before the
      obturator hernia was discovered. She presented to hospital with symptoms of bowel
      obstruction, and a computer tomography (CT) scan of her pelvis revealed an
      incarcerated obturator hernia. Her surgical management included reinforcement of
      the obturator foramen with sutures. A recurrence of the obturator hernia 2 years
      later required an extra-peritoneal mesh repair of the defect in the obturator
      foramen with a good outcome.

PMID- 18636224
TI  - The relationships between titers of anti-Ro or anti-La as measured by ELISA and
      salivary production rate with age correction.
AB  - The objective of this work was to clarify the clinical significance of titers of
      anti-Ro and anti-La, the relationships between titers of either anti-Ro or anti
      La, and salivary production rate (SPR). These autoantibodies were titrated using
      enzyme-linked immunosorbent assay. The Saxon test was performed to measure SPR.
      Fifty-one females who had anti-Ro but not anticentromere antibodies or anti-U1RNP
      were enrolled. SPR decreased significantly with age. In order to exclude the
      effect of aging on SPR, we calculated the "SPR with age correction." According to
      the results of a multiple regression analysis, only the anti-La titer was
      significantly associated with SPR with age correction. The distribution pattern
      of the anti-La titers consisted of two subgroups (with a titer index cutoff of
      100.0): a negative anti-La titer (anti-La<25.0) and low anti-La titer
      (25.0<or=anti-La<100.0) group, and a high anti-La titer group (anti-La>or=100.0).
      The concentration of serum IgG and the frequency of Sjogren's syndrome in the
      high anti-La titer group were significantly higher than those in the negative
      anti-La and low anti-La titer group. Several new aspects of the clinical
      significance of titrating anti-Ro and anti-La in comparison with SPR have been
      revealed.

PMID- 18636225
TI  - Telomeric nucleosomes: forgotten players at chromosome ends.
AB  - Telomeres are the special nucleoprotein structures that protect chromosome ends
      from both recombination and degradation. In most organisms, telomeric DNA
      consists of short sequences repeated in tandem ending in single-stranded G-rich
      overhangs. In higher eukaryotes, about 80% of telomeric DNA is organized in
      tightly packed nucleosomes separated by 10-20 bp of linker DNA. Several specific
      proteins contribute to telomeric structure. At the moment, a satisfactory
      description of telomere organization is still lacking. Whereas the role played by
      telomeric proteins in telomere function and regulation has been widely
      investigated, little is known about the contribution of nucleosomes to the
      protection of chromosome ends. In this review we present an overview on the
      chromatin organization in lower and higher eukaryotes, and discuss the recent
      results on the peculiar features of telomeric nucleosomes and on the epigenetic
      status of mammalian telomeres.

PMID- 18636226
TI  - Post-translational regulation of the tumor suppressor p27(KIP1).
AB  - Mitogenic signals stimulate cell division by activating cyclin/cyclin-dependent
      kinase (CDK) complexes. Their timely regulation ensures proper cell cycle
      progression. It is therefore not surprising that cyclin/CDK complexes are
      integrators of multiple signals from both the extracellular environment and
      intracellular cues. Important regulators of cyclin/CDKs are the CDK inhibitors
      that have attracted attention due to their association with disease. p27(KIP1) is
      a CDK inhibitor that controls CDK activity throughout the cell cycle. As a CDK
      inhibitor, p27(KIP1) has tumor suppressor activity. Besides CDKs, p27(KIP1)
      regulates additional cellular processes, including cell motility, some of which
      seem to mediate oncogenic activities of p27(KIP1). These activities of p27(KIP1)
      are regulated through multiple phosphorylation sites, targeted by several signal
      transduction pathways. Understanding functions and regulation of p27(KIP1) will
      be important to determine which isoform of p27(KIP1) has anti- or pro-tumorigenic
      activities. Such knowledge might be of prognostic value and may offer novel
      therapeutic windows.

PMID- 18636227
TI  - Primary percutaneous coronary intervention for ST-elevation myocardial infarction
      using an intravenous and subcutaneous enoxaparin low molecular weight heparin
      regimen.
AB  - BACKGROUND: Enoxaparin use in PCI has been investigated, however its role in
      primary PCI is less known. OBJECTIVE: To evaluate the role of combination IV + SC
      enoxaparin in primary PCI in STEMI. METHODS: 83 consecutive patients with STEMI
      who underwent primary PCI between January 1, 2005 and January 15, 2008 were
      included. Anticoagulation was based on our institution's STEMI protocol; either
      IV + SC enoxaparin, or IV unfractionated heparin (UFH). Clinical endpoints
      included MACE, bleeding and net adverse cardiac events (NACE). RESULTS: 45
      patients received UFH and 37 received IV + SC enoxaparin. There was no difference
      in the rate of mortality, MACE, or NACE. There was a trend toward more TIMI major
      and GUSTO moderate and severe bleeding in the UFH group. CONCLUSIONS: Application
      of IV + SC enoxaparin strategy for primary PCI in STEMI appears both safe and
      efficacious. A prospective randomized trial will be necessary to evaluate the
      safety and efficacy more thoroughly.

PMID- 18636228
TI  - Anticoagulation: where we are and where we need to go.
AB  - Although a commonly prescribed medication, warfarin has unique pharmacologic
      properties that make dosing challenging for many primary care physicians. When a
      patient's international normalized ratio (INR) is out of the therapeutic range,
      they are at increased risk for thrombotic or hemorrhagic complications. We have
      reviewed the current literature for quality improvement techniques to minimize
      adverse outcomes and improve anticoagulation care. The use of anticoagulation
      clinics, computer-guided dosing and patient self-monitoring have been
      demonstrated to reduce adverse events or improve patient and provider
      satisfaction. Additional techniques, including genetic-based dosing, concurrent
      vitamin K administration and development of risk-assessment tools, have been
      discussed, but not fully developed or assessed in the literature. We identify
      tools that can be implemented today as well as those currently under development
      for the improvement in anticoagulation care.

PMID- 18636229
TI  - Effects of rosuvastatin on platelet inhibition by clopidogrel in cardiovascular
      patients.
AB  - Statin interference has been suggested among the mechanisms of reduction of the
      antiplatelet effect of clopidogrel. We thus sought to assess the influence of
      rosuvastatin on clopidogrel antiplatelet action in high-risk (HR) cardiovascular
      patients. To set the level of platelet inhibition by combined antithrombotic
      treatments we retrospectively studied two populations of HR patients, one under
      aspirin alone, the other under aspirin plus rosuvastatin, before and after
      addition of clopidogrel. The effects of rosuvastatin compared with atorvastatin
      were then prospectively investigated in patients who underwent percutaneous
      coronary intervention (PCI), under clopidogrel and aspirin treatment. Light
      transmission platelet aggregation (LTA) was studied in response to adenosine
      diphosphate (ADP) (5 microM) or arachidonic acid (0.5 mM). The inhibitory effect
      of clopidogrel in reducing ADP-induced LTA was similar in the two HR groups of
      patients. No difference in ADP-induced platelet aggregation was observed in the
      two PCI groups of patients with either atorvastatin or rosuvastatin. In
      conclusion, rosuvastatin does not interfere with the antiplatelet effect of
      clopidogrel in patients with cardiovascular disease.

PMID- 18636230
TI  - Nucleotide polymorphism in the drought responsive gene Asr2 in wild populations
      of tomato.
AB  - The Asr gene family (named after abscicic acid [ABA], stress, ripening),
      exclusively present in plant genomes, is involved in transcriptional regulation.
      Its members are up-regulated in roots and leaves of water- or salt-stressed
      plants. In previous work, evidence of adaptive evolution (as inferred from
      synonymous and nonsynonymous divergence rates) has been reported for Asr2 in
      Solanum chilense and S. arcanum, two species dwelling in habitats with different
      precipitation regimes. In this paper we investigate patterns of intraspecific
      nucleotide variation in Asr2 and the unlinked locus CT114 in S. chilense and S.
      arcanum. The extent of nucleotide diversity in Asr2 differed between species in
      more than one order of magnitude. In both species we detected evidence of non
      neutral evolution, which may be ascribed to different selective regimes,
      potentially associated to unique climatic features, or, alternatively, to
      demographic events. The results are discussed in the light of demographic and
      selective hypotheses.

PMID- 18636231
TI  - Correlation of toxicity with lead content in root tip cells (Allium cepa L.).
AB  - The present study determines lead content in onion root tip cells (Allium cepa
      L.), correlating it with its toxicity. The treatment was carried at 25 +/- 0.5
      degrees C using aqueous solutions of lead chloride at 0.1, 0.25, 0.50, 0.75, and
      1 ppm for 12, 24, 48, and 72 h. For each treatment, a control where the lead
      solution was substituted by distilled water was included. After treatment, the
      meristems were fixed with a mixture of alcohol-acetic acid (3:1) and colored
      according to the technique of Feulgen. Lead content was quantified by graphite
      furnace absorption atomic spectrometry. The lead content in the roots ranged from
      3.25 to 244.72 microg/g dry weight, with a direct relation with the concentration
      and time of exposure. A significant negative correlation was presented (r = 
      0.3629; p < 0.01) among lead content and root growth increment, and a positive
      correlation (r = 0.7750; p < 0.01) with the induction of chromosomic aberrations.
      In conclusion, lead is able to induce a toxic effect in the exposed roots,
      correlated with its content.

PMID- 18636232
TI  - How does blood glucose control with metformin influence intensive insulin
      protocols? Evidence for involvement of oxidative stress and inflammatory
      cytokines.
AB  - INTRODUCTION: Recent investigations have revealed that control of hyperglycaemia
      with insulin improves outcomes. The cornerstone of hyperglycaemia in critically
      ill patients is insulin resistance and it remains refractory to intensive insulin
      protocols. We designed this study to evaluate the efficacy and safety of a new
      intensive insulin therapy (IIT) protocol combined with metformin. METHODS: Twenty
      one patients with systemic inflammatory response syndrome and a blood glucose
      level of >120 mg/dl admitted to an intensive care unit (ICU) were randomised to
      receive either intravenous infusion of IIT alone (n=11) or combined with
      metformin (IIT+MET; n=10) to maintain a blood glucose level (BGL) of 80-120
      mg/dl. Blood samples were obtained at baseline and at 48 hours, 96 hours and 7
      days after initiation of the study. Samples were analysed for interleukin-6 (IL
      6), tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO) as
      inflammatory mediators; plasminogen activation inhibitor-1 (PAI-1) as a
      coagulation mediator; and thiobarbituric reactive substances (TBARS), total
      antioxidant power (TAP) and total thiol molecules (TTM) as oxidative stress
      parameters. RESULTS: The addition of metformin to the IIT protocol decreased
      insulin requirement and concentration of insulin and C-peptide. With both
      treatments at most time points, the mean plasma levels of IL-6, TNF-alpha, NO,
      PAI-1 and TBARS were found to be significantly lower compared with baseline.
      Antioxidant activity was increased in both arms with increasing TAP and TTM
      (P<0.05). There was no significant difference between the two groups regarding
      reported beneficial effects on these parameters. Therapeutic Intervention Scoring
      System-28 (TISS-28) score, an index of nursing workload and number of therapeutic
      interventions, decreased in the IIT+MET group (P<0.01). We did not observe any
      occurrence of hyperlactataemia or acidosis in the IIT+MET group. CONCLUSION:
      Metformin plus insulin appears to lower the incidence of insulin resistance,
      lower insulin requirement while maintaining blood glucose level control, and
      consequently lower the incidence of adverse effects related to high-dose insulin
      therapy, particularly hypoglycaemia, and also declined nursing workload. Both
      treatment protocols showed improvements in inflammatory cytokine levels. Further
      studies with larger sample sizes are warranted to determine the undiscovered
      facts of insulin-sensitising agents in critically ill patients.

PMID- 18636233
TI  - Oxcarbazepine for the treatment of binge eating disorder: a case series.
AB  - We present a case series of nine obese outpatients with a diagnosis of binge
      eating disorder who were treated with a flexible dose of the anticonvulsant
      oxcarbazepine. The drug has not previously been used to treat this disorder. Five
      patients dropped out at various points of the study, giving only fragmented data.
      Where data were available, all patients reported side effects (n=7) and some
      showed a reduction (n=4) or no change (n=3) in binge episode frequency. Some
      patients lost weight over the study period (n=3; range, 3-5 kg); others showed no
      change (n=2) or an increase in weight (n=3; range, 1.8-2.9 kg). Our results were
      inconsistent, but the drug was effective for some patients who showed marked
      impulsivity in eating behaviours and depressive symptoms.

PMID- 18636234
TI  - The H-Wave device is an effective and safe non-pharmacological analgesic for
      chronic pain: a meta-analysis.
AB  - INTRODUCTION: This meta-analysis was conducted to systematically review the
      efficacy and safety of the H-Wave (Electronic Waveform Lab, Inc, Huntington
      Beach, CA, USA) device and programme as a non-pharmacological analgesic treatment
      in chronic soft tissue inflammation and neuropathic pain. METHODS: Five studies
      related to pain relief, reduction in pain medication and increased functionality
      obtained with the H-Wave device were included in the analysis. Data were analysed
      using the random effects model, including adjustment to evaluate variability,
      size of study and bias in effect size. A total of 6535 participants were included
      in the meta-analysis; there were 8065 participants' outcomes measured due to
      multiple measurements per participant. RESULTS: The H-Wave device decreased pain
      ratings across various chronic soft tissue inflammation and neuropathic pain
      conditions. The mean weighted effect size was 0.59, and the estimated effect size
      variance was 0.00003 (95% confidence intervals [CI]: 0.580, 0.600). The H-Wave
      device also decreased the intake of pain medication in patients with various
      chronic soft tissue inflammation and neuropathic pain conditions. The mean
      weighted effect size was 0.56, and the estimated effect size variance was
      0.000013 (95% CI: 0.553, 0.567). Patient functionality was also improved with use
      of the H-Wave device. The mean weighted effect size was 0.70, and the estimated
      effect size variance was 0.00002 (95% CI: 0.691, 0.709). A chi-square test for
      homogeneous effect sizes found highly significant (P<0.00001) variability,
      indicating a robust significant effect size for increased functionality relative
      to both pain relief and reduction in pain medication. There was little to no
      evidence of any adverse effects associated with the use of the H-Wave device.
      CONCLUSION: The findings indicate a moderate to strong effect of the H-Wave
      device in providing pain relief, reducing the requirement for pain medication and
      increasing functionality. The most robust effect was observed for improved
      functionality, suggesting that the H-Wave device may facilitate a quicker return
      to work and other related daily activities.

PMID- 18636235
TI  - Silencing GIRK4 expression in human atrial myocytes by adenovirus-delivered small
      hairpin RNA.
AB  - GIRK4 has been shown to be a subunit of I(KACh), and the use of GIRK4 in human
      atrial myocytes to treat arrhythmia remains an important research pursuit.
      Adenovirus-delivered small hairpin RNA (shRNA) has been used to mediate gene
      knockdown in mouse cardiocytes, yet there is no information on the successful
      application of this technique in human cardiocytes. In the current study, we used
      a siRNA validation system to select the most efficient sequence for silencing
      GIRK4. To this end, adenovirus-delivered shRNA, which expresses this sequence,
      was used to silence GIRK4 expression in human atrial myocytes. Finally, the
      feasibility, challenges, and results of silencing GIRK4 expression were evaluated
      by RT-PCR, western blotting, and the voltage-clamp technique. The levels of mRNA
      and protein were depressed significantly in cells infected by adenovirus
      delivered shRNA against GIRK4, approximately 86.3% and 51.1% lower than those
      cells infected by adenovirus-delivered nonsense shRNA, respectively. At the same
      time, I(KACh) densities were decreased 53% by adenovirus-delivered shRNA against
      GIRK4. In summary, adenovirus-delivered shRNA against GIRK4 mediated efficient
      GIRK4 knockdown in human atrial myocytes and decreased I(KACh) densities. As
      such, these data indicated that adenovirus-delivered shRNA against GIRK4 is a
      potential tool for treating arrhythmia.

PMID- 18636237
TI  - [Methicillin-resistant Staphylococcus aureus (MRSA). Relevance in dermatology].
AB  - Because of the increasing incidence of resistance to beta-lactam antibiotics,
      dermatologists will be increasingly confronted with methicillin-resistant S.
      aureus (MRSA) strains which display a great variability of their virulence
      factors. In view of the high mortality of systemic MRSA infections (estimated 700
      1.500 deaths per year in Germany), dermatologists should be well aware of the
      various aspects of diagnosis, therapy and prevention of this problem bacteria.
      Adequate screening measures must be in place to identify high-risk patients and
      institute appropriate prophylactic measures and therapy. If only colonization is
      present, topical antiseptic measures are sufficient. If an infection is present,
      either systemic or topical therapeutic approaches may be indicated. We review the
      role of MRSA infection and colonization in skin diseases.

PMID- 18636236
TI  - Molecular characterization of Pegarn: a Drosophila homolog of UNC-51 kinase.
AB  - We have isolated and characterized the gene encoding a Drosophila melanogaster
      homolog of Caenorhabditis elegans UNC-51 (uncoordinated movement-51): Pegarn.
      Developmental Northern blot shows the Pegarn gene is expressed at all stages of
      development. The protein is detected throughout the Drosophila third instar
      larval central nervous system (CNS) in axons projecting out from the ventral
      ganglion and in the optic anlagen of the optic lobe. Heterozygous Pegarn mutant
      embryos show defects in larval axonal neuronal patterning, but survive to
      adulthood. Homozygous mutants have an even more deformed pattern of neuronal
      development and do not survive through the larval stages. The data from this
      research suggest the critical roles of Pegarn in CNS and PNS axonal formation in
      Drosophila melanogaster and indicates its similar role in other multicellular
      species.

PMID- 18636238
TI  - A copper(II)-selective chelator ameliorates diabetes-evoked renal fibrosis and
      albuminuria, and suppresses pathogenic TGF-beta activation in the kidneys of rats
      used as a model of diabetes.
AB  - AIMS/HYPOTHESIS: The selective Cu(II) chelator triethylenetetramine (TETA)
      extracts systemic Cu(II) into the urine of diabetic humans and rats as a model of
      diabetes, and in the process also normalises hallmarks of diabetic heart disease.
      However, the role of Cu and its response to TETA in animals with diabetic
      nephropathy were previously unknown. Here, we report the effects of TETA
      treatment on Cu and other essential elements, as well as on indices of renal
      injury and known pathogenic molecular processes, in kidneys from a rat model of
      diabetes. METHODS: Rats at 8 weeks after streptozotocin-induction of diabetes
      were treated with oral TETA (34 mg/day in drinking water) for a further 8 weeks
      and then compared with untreated diabetic control animals. RESULTS: Renal tissue
      Cu was substantively elevated by diabetes and normalised by TETA, which also
      suppressed whole-kidney and glomerular hypertrophy without lowering blood
      glucose. The urinary albumin: creatinine ratio was significantly elevated in the
      rat model of diabetes but lowered by TETA. Total collagen was also elevated in
      diabetic kidneys and significantly improved by TETA. Furthermore, renal cortex
      levels of TGF-beta1, MAD homologue (SMAD) 4, phosphorylated SMAD2, fibronectin-1,
      collagen-III, collagen-IV, plasminogen activator inhibitor-1 and semicarbazide
      sensitive amine oxidase all tended to be elevated in diabetes and normalised by
      TETA. CONCLUSIONS/INTERPRETATION: Dysregulation of renal Cu homeostasis may be a
      key event eliciting development of diabetic nephropathy. Selective Cu(II)
      chelation can protect against pathogenic mechanisms that lead to or cause
      diabetic nephropathy and might be clinically useful in the treatment of early
      stage diabetic kidney disease.

PMID- 18636240
TI  - Comment on "impact of recent intravenous chemotherapy on outcome in severe sepsis
      and septic shock patients with haematological malignancies" by Vandijck et al.

PMID- 18636241
TI  - Arsenic-induced suicidal erythrocyte death.
AB  - Environmental exposure to arsenic has been associated with anemia, which could
      result from suicidal erythrocyte death or eryptosis, characterized by cell
      shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptosis
      is triggered by increase in cytosolic Ca2+ concentration, ceramide and energy
      depletion. The present experiments explored, whether arsenic stimulates
      eryptosis. According to annexin V-binding, arsenic trioxide (7 microM) within 48
      h significantly increased phosphatidylserine exposure of human erythrocytes
      without inducing hemolysis. According to forward scatter, arsenic trioxide (7
      microM) significantly decreased cell volume. Moreover, Fluo3-fluorescence showed
      that arsenic (10 microM) significantly increased cytosolic Ca2+ concentration.
      According to binding of respective fluorescent antibodies, arsenic trioxide (10
      microM) significantly increased ceramide formation. Arsenic (10 microM) further
      lowered the intracellular ATP concentration. Removal of extracellular Ca2+ or
      inhibition of the Ca2+-permeable cation channels with amiloride blunted the
      effects of arsenic on annexin V-binding and cell shrinkage. In conclusion,
      arsenic triggers suicidal erythrocyte death by increasing cytosolic Ca2+
      concentration, by stimulating the formation of ceramide and by decreasing ATP
      availability.

PMID- 18636242
TI  - Distinct subtypes of urinary bladder epithelial cells with inducible and non
      inducible cytochrome P450 1A1.
AB  - Cultured primary porcine urinary bladder epithelial cells (PUBEC) represent an
      adequate and easy to handle in vitro system for studies of urothelial toxicity.
      PUBEC maintain in vivo-like metabolic activities and physiological functions.
      They express inducible cytochrome P4501A isoenzymes, which are of particular
      relevance, since they contribute to activation of bladder carcinogens. A possible
      drawback of PUBEC is their isolation from common domestic pigs that do not
      represent an inbred strain. In order to further establish PUBEC as a standard in
      vitro toxicity test system we analysed possible interindividual differences in
      CYP1A1 inducibility. Interestingly, we observed by flow cytometry that PUBEC
      obtained from individual pigs consist of two distinct subpopulations with
      inducible and non-inducible cells. A strong, concentration-dependent CYP1A1
      induction was observed in the responsive subpopulation when incubated with
      benzo[a]pyrene (B[a]P) in a concentration range between 1 and 10 muM. In
      contrast, no CYP1A1 induction was obtained in the non-responsive subpopulation up
      to the highest tested concentrations of 100 muM. The fraction of responsive cells
      showed large interindividual differences ranging from 10 to 65% of the total cell
      number. For practical purposes it might be reasonable to analyse pools of PUBEC
      from five pigs which substantially reduce batch to batch variability. In
      conclusion, we have identified two functionally distinct subpopulations of
      urinary bladder epithelial cells. It will be interesting to study whether the
      CYP1A inducible subtype is more susceptible to bladder carcinogens.

PMID- 18636243
TI  - Some effects of dopamine transporter and receptor ligands on discriminative
      stimulus, physiologic, and directly observable indices of opioid withdrawal in
      rhesus monkeys.
AB  - RATIONALE: Some monoamine uptake inhibitors (e.g., cocaine) attenuate the
      subjective and discriminative stimulus effects of opioid withdrawal. OBJECTIVE:
      This study examined a role for dopamine transporters and receptors as targets for
      drugs to modify the discriminative stimulus effects of opioid withdrawal and
      further examined a subset of these drugs for their capacity to modify some
      directly observable and physiologic indices of withdrawal. MATERIALS AND METHODS:
      Rhesus monkeys receiving 2 mg/kg/day of L: -alpha-acetylmethadol discriminated
      the opioid antagonist naltrexone (0.0178 mg/kg s.c.). RESULTS: The naltrexone
      discriminative stimulus was attenuated not only by the mu agonist morphine but
      also by the dopamine D(2)-like receptor agonists bromocryptine and quinpirole. In
      contrast, the naltrexone discriminative stimulus was not consistently modified by
      the non-selective, D(1)- and D(2)-like agonist apomorphine or by uptake
      inhibitors with high selectivity for dopamine transporters (GBR 12909, RTI 113,
      and RTI 177). In the same monkeys, naltrexone dose dependently decreased body
      temperature, increased breathing frequency, and induced directly observable signs
      (grimacing, salivation, and unusual posture). Hypothermia, hyperventilation, and
      signs of withdrawal were significantly attenuated by morphine and not by
      quinpirole. CONCLUSIONS: Attenuation of opioid withdrawal by D(2)-like receptor
      agonists that have lower efficacy than dopamine, and not by uptake inhibitors
      with selectivity for dopamine transporters, suggests that magnitude of receptor
      stimulation (e.g., efficacy) and selectivity at dopamine receptors are important
      factors in the modulation of opioid withdrawal. Attenuation of the naltrexone
      discriminative stimulus by drugs that inhibit both dopamine and serotonin uptake
      (e.g., cocaine) could result from an inhibitory effect of serotonin on dopamine.
      The role of dopamine in opioid withdrawal appears to be restricted to subjective
      (i.e., not somatic) indices [corrected]

PMID- 18636244
TI  - Conductive polymer as a controlled microenvironment for the potentiometric high
      throughput evaluation of ionic liquid cell toxicity.
AB  - This paper presents both biological and potentiometric evaluations of the cell
      toxicity of a widely used ionic liquid, 1-butyl-3-methylimidazolium
      tetrafluoroborate ([bmim]BF(4)), to Chinese hamster lung fibroblast cells (V79
      cell line). The innovative potentiometric study takes advantage of the unique
      properties of conductive polymer polypyrrole (PPY) for the potentiometric
      evaluation of cell toxicity of [bmim]BF(4) to the V79 cells in a real-time,
      noninvasive and high-throughput manner. The conductive polymer PPY provides a
      controlled microenvironment that allows the quantitative release of the anions of
      the ionic liquids into the cells being monitored in real time and noninvasively.
      Parallel biological assay results showed that V79 cells exposed to [bmim]BF(4)
      usually grew in clusters, and that many small vacuoles could be seen in the
      cytoplasm. At the 24th hour after the V79 cells had been exposed to the ionic
      liquid (IL), the half inhibition concentration (EC(50)) of [bmim]BF(4) was around
      5 mM. From a cell cycle study performed using a FACScan flow cytometer, it was
      found that the V79 cells could be partially locked to the G(1) phase by
      [bmim]BF(4), which extended the doubling time for cell growth. Comparing with the
      EC(50) values of cadmium chloride and mercury chloride, [bmim]BF(4) is not very
      toxic, but it may have a long-term toxic effect on mammalian cells. Compared to
      traditional biological in vitro assays, the use of a conductive polymer substrate
      in combination with a potentiometric sensor array is much more sensitive, faster,
      and enables a simpler evaluation of chemical cell toxicity. Additionally, it
      simplifies the study of the reversibility of cell toxicity, i.e., cell recovery,
      because there is no need to refresh the culture medium since a finite amount of
      chemicals can be doped and released. We found that the cytotoxicity of
      [bmim]BF(4) at a concentration of less than 6 mM was reversible for the V79 cell
      line, because cell morphology and proliferation rate returned to normal after the
      removal of the IL from the culture medium. This finding suggests that the IL
      [bmim]BF(4) could be used as a tool to control mammalian cell proliferation rate.

PMID- 18636246
TI  - FT-IR spectral imaging of blood vessels reveals protein secondary structure
      deviations induced by tumor growth.
AB  - Vascular basement membrane remodeling is involved in tumor angiogenesis to enable
      tumor invasion and growth. FT-IR spectral imaging was used to determine changes
      in tumor blood vessels to reveal protein secondary structure in Rag-gamma immuno
      deficient mice sacrificed 14 and 21 days after subcutaneous glioma implantation.
      For the oldest blood capillaries (diameter >20 microns), tumor growth induced a
      decrease in triple-helix content (1638 cm(-1); -7.3%; P < 0.05) and an increase
      in beta turns (1666 and 1615 cm(-1); +4%; P < 0.01). These protein-structure
      alterations, mainly from type IV collagen, reflected the high angiogenic stress
      of growing tumors. We propose to use these molecular markers of vascular basement
      membrane protein alterations for gradation of solid tumors by FT-IR spectral
      imaging.

PMID- 18636247
TI  - Association of MDR1, CYP3A4*18B, and CYP3A5*3 polymorphisms with cyclosporine
      pharmacokinetics in Chinese renal transplant recipients.
AB  - OBJECTIVE: The objective of this study was to retrospectively evaluate the
      effects of MDR1, CYP3A4*18B, and CYP3A5*3 genetic polymorphisms on cyclosporine A
      (CsA) pharmacokinetics in Chinese renal transplant patients during the first
      month after transplantation. METHODS: A total of 103 renal transplant recipients
      receiving CsA were genotyped for MDR1 (C1236T, G2677T/A, and C3435T), CYP3A4*18B,
      and CYP3A5*3. The predose and 2-h postdose concentrations of CsA (C(0) and C(2),
      respectively) were determined by fluorescence polarization immunoassay, and their
      relationships with corresponding genotypes and haplotypes were investigated.
      RESULTS: Patients with a CYP3A4*1/*1 genotype were found to have a higher dose
      adjusted concentration compared with those with CYP3A4*18B/*18B, as follows: for
      C(2), 19.3% (P = 0.008) during days 8-15, 35.2% (P = 0.008) during days 16-30,
      and for C(0), 39.7% (P = 0.012) during days 16-30. The dose-adjusted C(0) was
      higher in patients with MDR1 1236CC compared with those with 1236TT in the first
      month postoperation. The dose-adjusted C(0) in patients with the CYP3A5*3/*3
      genotype was 25.5% and 30.7% higher than those with the wild-type genotype during
      days 8-15 (P = 0.011) and days 16-30 (P = 0.015), respectively. Haplotype
      analysis revealed that the dose-adjusted C(0) was higher in the first month
      following surgery in carriers of haplotype MDR1 CAC than in noncarriers.
      Polymorphisms of MDR1 and CYP3A5*3 did not affect dose-adjusted C(2.) CONCLUSION:
      The data suggests that the CYP3A4*18B genotype affects CsA pharmacokinetics
      during the first month following surgery in Chinese renal transplant recipients.
      Patients with CYP3A4*18B alleles may require higher doses of CsA to reach the
      target levels. Large prospective studies may be needed to further explore the
      impact of MDR1 and CYP3A5*3 polymorphisms on CsA pharmacokinetics in renal
      transplant recipients.

PMID- 18636248
TI  - The anterior medullary-anterior pontomesencephalic venous system and its bridging
      veins communicating to the dural sinuses: normal anatomy and drainage routes from
      dural arteriovenous fistulas.
AB  - INTRODUCTION: We evaluated the normal venous anatomy of the anterior
      medullary/anterior pontomesencephalic venous (AMV/APMV) system and bridging veins
      connected to the dural sinuses using magnetic resonance (MR) imaging and
      demonstrated cases of dural arteriovenous fistulas (DAVFs) with bridging venous
      drainage. MATERIALS AND METHODS: MR images obtained using a 3D gradient echo
      sequence in 70 patients without lesions affecting the deep or posterior venous
      channels were reviewed to evaluate the normal anatomy of the AMV/APMV system and
      bridging veins. MR images and digital subtraction angiography in 80 cases with
      intracranial or craniocervical junction DAVFs were reviewed to evaluate the
      bridging venous drainage from DAVFs. RESULTS: MR images clearly revealed AMV/APMV
      in 35 cases. Fifteen cases showed a direct connection between AMV and APMV, while
      15 cases showed an indirect communication via the transverse pontine vein or the
      bridging vein. In the five remaining cases, the AMV and APMV end separately to
      the bridging vein or the transverse pontine vein. Bridging veins were identified
      in 34 cases, connecting to the cavernous sinus in 33, to the suboccipital
      cavernous sinus in 11, and the inferior petrosal sinus in five cases. In 80 DAVF
      cases, seven of 40 cavernous sinus DAVFs, two craniocervical junction DAVFs, and
      one inferior petrosal sinus DAVF drained via bridging veins to the brain stem.
      CONCLUSION: The AMV/APMV and bridging veins showed various anatomies and
      frequently showed a connection to the cavernous sinus. Knowledge of the venous
      anatomy is helpful for the diagnosis and intravascular treatment of DAVFs.

PMID- 18636249
TI  - MRA artefacts with Nexus coils.

PMID- 18636250
TI  - Methylmalonic acidemia: brain imaging findings in 52 children and a review of the
      literature.
AB  - BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal-recessive inborn error
      of metabolism. OBJECTIVE: To recognize the CT and MR brain sectional imaging
      findings in children with MMA. MATERIALS AND METHODS: Brain imaging studies (47
      MR and 5 CT studies) from 52 children were reviewed and reported by a
      neuroradiologist. The clinical data were collected for each patient. RESULTS: The
      most common findings were ventricular dilation (17 studies), cortical atrophy
      (15), periventricular white matter abnormality (12), thinning of the corpus
      callosum (8), subcortical white matter abnormality (6), cerebellar atrophy (4),
      basal ganglionic calcification (3), and myelination delay (3). The brain images
      in 14 patients were normal. CONCLUSION: Radiological findings of MMA are
      nonspecific. A constellation of common clinical and radiological findings should
      raise the suspicion of MMA.

PMID- 18636251
TI  - Whole-body MR imaging with the use of parallel imaging for detection of skeletal
      metastases in pediatric patients with small-cell neoplasms: comparison with
      skeletal scintigraphy and FDG PET/CT.
AB  - BACKGROUND: In pediatric patients with small-cell tumors, there is an increasing
      demand for accurate and early detection of skeletal, especially bone marrow,
      metastases as new treatment protocols are introduced. Whole-body MR imaging (WB
      MR) and (18)F-fluorodeoxyglucose PET/CT (FDG PET/CT) are new promising imaging
      methods that can detect metastases before osteoblastic host response occurs,
      which is the basis for detection of metastases by skeletal scintigraphy (SSC).
      OBJECTIVE: To assess the ability of WB-MR to detect marrow metastases in children
      with small-cell neoplasms and compare its performance with that of FDG PET/CT and
      SSC. MATERIALS AND METHODS: During a 16-month period, 26 children and adolescents
      with histopathologically proven small-cell neoplasms underwent WB-MR, FDG PET/CT
      and Tc-phosphonate-based SSC in a random order within a 25-day period. Metastases
      were localized in relation to eight regions of the body. RESULTS: WB-MR revealed
      metastases in 39 out of a total of 208 regions in 26 patients (sensitivity 97.5%,
      specificity 99.4%, positive predictive value 97.5%, negative predictive value
      99.4%), SSC in 12 regions (sensitivity 30%, specificity 99.4%, PPV 92.3%, NPV
      85.6%) and FDG PET/CT in 36 regions (sensitivity 90.0%, specificity 100%, PPV
      100%, NPV 97.7%). Both WB-MR and FDG PET/CT showed excellent agreement (kappa)
      with the final diagnosis (96.9% and 93.6% respectively), whereas SSC showed only
      moderate agreement (39.6%). CONCLUSION: Our results suggest that WB-MR and FDG
      PET/CT studies are robust imaging modalities for screening for skeletal
      metastases, and are far more accurate than SSC. The lack of radiation is an
      additional advantage of WB-MR, especially in the pediatric population.

PMID- 18636252
TI  - Identification of novel major histocompatibility complex class I sequences in a
      marsupial, the brushtail possum (Trichosurus vulpecula).
AB  - The major histocompatibility complex (MHC) is an essential part of the vertebrate
      immune response. MHC genes may be classified as classical, non-classical or non
      functional pseudogenes. We have investigated the diversity of class I MHC genes
      in the brushtail possum, a marsupial native to Australia and an introduced pest
      in New Zealand. The MHC of marsupials is poorly characterised compared to
      eutherian mammal species. Comparisons between marsupials and eutherians may
      enhance understanding of the evolution and functions of this important genetic
      region. We found a high level of diversity in possum class I MHC genes. Twenty
      novel sequences were identified using polymerase chain reaction (PCR) primers
      designed from existing marsupial class I MHC genes. Eleven of these sequences
      shared a high level of homology with the only previously identified possum MHC
      class I gene TrvuUB and appear to be alleles at a single locus. Another seven
      sequences are also similar to TrvuUB but have frame-shift mutations or stop
      codons early in their sequence, suggesting they are non-functional alleles of a
      pseudogene locus. The remaining sequences are highly divergent from other possum
      sequences and clusters with American marsupials in phylogenetic analysis,
      indicating they may have changed little since the separation of Australian and
      American marsupials.

PMID- 18636253
TI  - Accumulation of prenyl alcohols by terpenoid biosynthesis inhibitors in various
      microorganisms.
AB  - Squalene synthase inhibitors significantly accelerate the production of farnesol
      by various microorganisms. However, farnesol production by Saccharomyces
      cerevisiae ATCC 64031, in which the squalene synthase gene is deleted, was not
      affected by the inhibitors, indicating that farnesol accumulation is enhanced in
      the absence of squalene synthase activity. The combination of diphenylamine as an
      inhibitor of carotenoid biosynthesis and a squalene synthase inhibitor increases
      geranylgeraniol production by a yeast, Rhodotorula rubra NBRC 0870. An ent-kauren
      synthase inhibitor also enhances the production of farnesol and geranylgeraniol
      by a filamentous fungus, Gibberella fujikuroi NBRC 30336. These results indicate
      that the inhibition of downstream enzymes from prenyl diphosphate synthase leads
      to the production of farnesol and geranylgeraniol.

PMID- 18636254
TI  - Identification of immunogenic polypeptides from a Mycoplasma hyopneumoniae genome
      library by phage display.
AB  - The identification of immunogenic polypeptides of pathogens is helpful for the
      development of diagnostic assays and therapeutic applications like vaccines.
      Routinely, these proteins are identified by two-dimensional polyacrylamide gel
      electrophoresis and Western blot using convalescent serum, followed by mass
      spectrometry. This technology, however, is limited, because low or differentially
      expressed proteins, e.g. dependent on pathogen-host interaction, cannot be
      identified. In this work, we developed and improved a M13 genomic phage display
      based method for the selection of immunogenic polypeptides of Mycoplasma
      hyopneumoniae, a pathogen causing porcine enzootic pneumonia. The fragmented
      genome of M. hyopneumoniae was cloned into a phage display vector, and the
      genomic library was packaged using the helperphage Hyperphage to enrich open
      reading frames (ORFs). Afterwards, the phage display library was screened by
      panning using convalescent serum. The analysis of individual phage clones
      resulted in the identification of five genes encoding immunogenic proteins, only
      two of which had been previously identified and described as immunogenic. This
      M13 genomic phage display, directly combining ORF enrichment and the presentation
      of the corresponding polypeptide on the phage surface, complements proteome-based
      methods for the identification of immunogenic polypeptides and is particularly
      well suited for the use in mycoplasma species.

PMID- 18636255
TI  - Deep-sea thermophilic Geobacillus bacteriophage GVE2 transcriptional profile and
      proteomic characterization of virions.
AB  - Thermophilic bacteria and viruses represent novel sources of genetic materials
      and enzymes with great potential for use in industry and biotechnology. In this
      study, GVE2, a virulent tailed Siphoviridae bacteriophage infecting deep-sea
      thermophilic Geobacillus sp. E263, was characterized. The bacteriophage contained
      a 40,863-bp linear double-stranded genomic deoxyribonucleic acid (DNA) with 62
      presumptive open reading frames (ORFs). A viral DNA microarray was developed to
      monitor the viral gene transcription program. Microarray analysis indicated that
      74.2% of the presumptive ORFs were expressed. The structural proteins of purified
      GVE2 virions were identified by mass spectrometric analysis. The purified virions
      contained six protein bands. Of the newly retrieved proteins, VP371 was further
      characterized. The immuno-electron microscopy indicated that the VP371 protein
      was a component of the viral capsid. Transcriptional analyses and proteomic
      characterization of GVE2 would be helpful to understand the complex host-virus
      interaction during virus infection.

PMID- 18636256
TI  - Fungal secretomes--nature's toolbox for white biotechnology.
AB  - Adapting their metabolism to varying carbon and nitrogen sources, saprophytic
      fungi produce an arsenal of extracellular enzymes, the secretome, which allows
      for an efficient degradation of lignocelluloses and further biopolymers. Based on
      fundamental advances in electrophoretic, chromatographic, and mass spectrometric
      techniques on the one hand and the availability of annotated fungal genomes and
      sophisticated bioinformatic software tools on the other hand, a detailed analysis
      of fungal secretomes has become feasible. While a number of reports on
      ascomycetous secretomes of, e.g., Aspergillus, Trichoderma, and Fusarium species
      are already available, studies on basidiomycetes have been mainly focused on the
      two model organisms Phanerochaete chrysosporium and Coprinopsis cinerea so far.
      Though an impressive number and diversity of fungal biocatalysts has been
      revealed by secretome analyses, the identity and function of many extracellular
      proteins still remains to be elucidated. A comprehensive understanding of the
      qualitative and quantitative composition of fungal secretomes, together with
      their synergistic actions and kinetic expression profiles, will allow for the
      development of optimized enzyme cocktails for white biotechnology.

PMID- 18636257
TI  - Myoelectric hand prostheses in very young children.
AB  - Myoelectric prostheses have generally been provided for adolescent or adult
      patients. The availability of smaller-sized electric hands has enabled the
      introduction of myoelectric prostheses to preschool children, mainly in the
      Scandinavian countries. This study evaluates the acceptance of myoelectric
      prostheses in 41 children with unilateral upper limb deficiency between the ages
      of two and five years. The prosthesis was used for an average time of 5.8 hours
      per day. The level of amputation was found to influence the acceptance rate.
      Furthermore, prosthetic use training by an occupational therapist is related to
      successful use of the prosthesis. The general drop-out rate in preschool children
      is very low compared to adults. Therefore, infants can profit from myoelectric
      hand prostheses. Since a correct indication and an intense training program
      significantly influence the acceptance rate, introduction of myoelectric
      prostheses to preschool children should take place at specialised centres with an
      interdisciplinary team.

PMID- 18636258
TI  - Hemilaminoplasty for the treatment of lumbar disc herniation.
AB  - The aim of this study was to evaluate the clinical outcome of the
      hemilaminoplasty technique for the treatment of lumbar disc herniation (LDH).
      Forty-three cases of single-level LDH underwent a discectomy and hemilaminoplasty
      procedure. The preoperative JOA score and VAS of lower back and leg pain were
      10.4+/-1.3, 7.8+/-2.1, and 8.6+/-1.7, respectively. The Cobb angle of lumbar
      sagittal alignment was 10.1+/-2.0. Twenty-five patients who agreed to lumbar
      discectomy through fenestration were enrolled as the control group. The
      postoperative JOA score and VAS of low back and leg pain of the hemilaminoplasty
      group were 19.4+/-1.3, 1.4+/-0.4, and 2.1+/-0.5, respectively. The Cobb angle was
      29.2+/-1.9 degrees. There was no epidural scar observed in any of the patients.
      The Cobb angle of the hemilaminoplasty group was higher than that of the control
      group (p < 0.05), while the VAS was significantly lower (p < 0.05).
      Hemilaminoplasty is a useful method to improve clinical outcome, prevent epidural
      scar, and preserve the normal alignment of lumbar spine.

PMID- 18636259
TI  - Commercial LightCycler-based quantitative real-time PCR compared to nested PCR
      for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma.
AB  - Translocation of chromosomes 14 and 18 [t(14;18)] for detection of minimal
      residual disease in follicular lymphoma patients can be analyzed by nested
      polymerase chain reaction (PCR) or by quantitative PCR like LightCycler-based
      assays. We have compared both methods in blood and bone marrow samples of 28
      patients enrolled in a clinical study on immunochemotherapy. In 42% of samples,
      the bcl2-IgH rearrangement was detectable by nested PCR, but not by LightCycler
      PCR. Nested PCR was able to reveal a significant drop in positive bone marrow or
      peripheral blood samples after therapy. In contrast, with LightCycler PCR, the
      detected drop in t(14;18)-positive cells did not reach statistical significance.
      The majority of patients showed positive results with nested PCR of peripheral
      blood or bone marrow without any associations to presence or absence of
      histological bone marrow (BM) infiltration by lymphoma cells. With LightCycler
      PCR, the numbers of positive cells were higher in samples from patients with BM
      infiltration of lymphoma cells (1.9 x 10(-2)) compared to samples from patients
      without involvement (4.08 x 10(-5)). A similar trend was seen in samples derived
      from the peripheral blood. Positivity for t(14;18) after therapy in two patients
      correlated with clinical relapse 6 months later. The data shown here demonstrate
      a lower sensitivity of LightCycler vs. nested PCR for detection of t(14;18). The
      usefulness of nested PCR for t(14;18) for risk stratification after primary
      therapy has to be validated in larger trials.

PMID- 18636260
TI  - Influence of conditioning regimens and stem cell sources on donor-type chimerism
      early after stem cell transplantation.
AB  - We retrospectively analyzed very early chimerism before and ongoing neutrophil
      engraftment (days 7, 14, 21, 28) and investigated the influence of conditioning
      regimens and stem cell sources on donor-type chimerism in 59 Japanese patients
      who had received allogeneic hematopoietic stem cell transplantation. The
      percentage of donor-type chimerism increased before engraftment in all patients
      who achieved engraftment. The average percentage of donor-type chimerism in
      patients who had received reduced-intensity stem cell transplantation (RIST) with
      total body irradiation (TBI) was significantly higher than that in patients who
      had received RIST without TBI (98.8% vs 87.5% on day 21, P<0.01; 99.3% vs 84.3%
      on day 28, P<0.01). The average percentage of donor-type chimerism after
      peripheral blood stem cell transplantation was significantly higher than that
      after bone marrow transplantation on day 7 (81.5% vs 43.1%, P<0.01), and the
      average percentage of donor-type chimerism after cord blood transplantation was
      significantly lower on day 14 (55.8% vs 84.8%, P<0.05). Compared with the average
      percentage of donor-type chimerism in patients who achieved engraftment with each
      stem cell source, a notable decrease in donor-type chimerism was observed in
      patients who failed to achieve engraftment. This study suggests that differences
      in conditioning regimens and stem cell sources should be taken into account when
      considering donor-type chimerism.

PMID- 18636261
TI  - Efficiency of antiviral therapy plus IVIG in a case of primary EBV infection
      associated PTLD refractory to rituximab, chemotherapy, and antiviral therapy
      alone.

PMID- 18636262
TI  - Activity of the 5' regulatory regions of the rice polyubiquitin rubi3 gene in
      transgenic rice plants as analyzed by both GUS and GFP reporter genes.
AB  - Ubiquitin is an abundant protein involved in protein degradation and cell cycle
      control in plants and rubi3 is a polyubiquitin gene isolated from rice (Oryza
      sativa L.). Using both GFP and GUS as reporter genes, we analyzed the expression
      pattern of the rubi3 promoter as well as the effects of the rubi3 5'-UTR (5'
      untranslated region) intron and the 5' terminal 27 bp of the rubi3 coding
      sequence on the activity of the promoter in transgenic rice plants. The rubi3
      promoter with the 5'-UTR intron was active in all the tissue and cell types
      examined and supported more constitutive expression of reporter genes than the
      maize Ubi-1 promoter. The rubi3 5'-UTR intron mediated enhancement on the
      activity of its promoter in a tissue-specific manner but did not alter its
      overall expression pattern. The enhancement was particularly intense in roots,
      pollen grains, inner tissue of ovaries, and embryos and aleurone layers in
      maturing seeds. The translational fusion of the first 27 bp of the rubi3 coding
      sequence to GUS gene further enhanced GUS expression directed by the rubi3
      promoter in all the tissues examined. The rubi3 promoter should be an important
      addition to the arsenal of strong and constitutive promoters for monocot
      transformation and biotechnology.

PMID- 18636263
TI  - Penile preserving surgery and surgical strategies to maximize penile form and
      function in penile cancer: recommendations from the United Kingdom experience.
AB  - OBJECTIVES: The diagnosis of penile cancer can be devastating for a man and his
      partner. The fear of cancer is heightened by the prospect of penile amputation.
      While conventional radical surgery continues to be an effective approach to
      management, the emasculating nature of this treatment has serious psychological
      and sexual morbidity. Recent studies have challenged the traditional belief that
      a 2 cm margin was required for adequate oncological control. METHODS: We review
      the current options and status of such penile preserving techniques in the modern
      day management of penile cancer, and assess the use of the different techniques
      according to the stage and grade of disease based upon the combined experience of
      two superregional centres in the United Kingdom. RESULTS: A range of organ
      preserving procedures matches the clinical spectrum of patients presenting with
      penile cancer. These demonstrate excellent oncological control whilst maximizing
      penile function and form. CONCLUSION: Innovative surgical techniques can now
      preserve as much penile tissue and functional integrity as possible, without
      compromising oncological control. This minimizes the impact of disease and its
      treatment on the quality of life of the patient.

PMID- 18636264
TI  - Radiation therapy in the management of the primary penile tumor: an update.
AB  - OBJECTIVES: Squamous carcinoma of the penis is rare but psychologically
      devastating and potentially fatal. Radiotherapy offers a penile-conserving
      treatment option without jeopardizing cure. We have used primary penile
      brachytherapy as the treatment of choice for T1, T2 and selected T3 patients
      since 1989 and present updated results for 67 patients. METHODS: Mean age was 60
      years (range 22-93). Stage was T1 in 56%, T2: 33%, T3: 8%, and Tx: 3%. Grade was
      moderate or poorly differentiated in 48%. In Toronto after-loading pulse dose
      rate (PDR) brachytherapy (n = 41) was used for all treatments while Ottawa used
      manually loaded Iridium(192) (n = 26). Two or three parallel planes of needles
      (median 6) were inserted using pre-drilled lucite templates for guidance and
      fixation; 60 Gy was delivered over 4-5 days. RESULTS: Median follow-up is 4 years
      (range 0.2-16.2). At 10 years, actuarial overall survival is 59%, cause specific
      survival 83.6%. Nine men died of penile cancer and eight of other causes with no
      evidence of recurrence. Penectomy was required for eight local failures and two
      necroses, for an actuarial penile preservation rate at 5 years of 88% and 10
      years of 67%. The soft tissue necrosis rate is 12% and the urethral stenosis rate
      9%. Six of 11 regional failures were salvaged by lymph node dissection +/-
      external radiation. The other five all had concurrent distant failure and died of
      disease. CONCLUSIONS: Brachytherapy is an effective treatment for T1, T2 and
      selected T3 SCC of the penis. Close follow-up is mandatory as local failures and
      many regional failures can be salvaged by surgery.

PMID- 18636265
TI  - [OCT-based re-injections for anti-VEGF-treatment for neovascular ARMD].
AB  - BACKGROUND: We present an optical coherence tomography (OCT)-based individual
      reinjection procedure for bevacizumab treatment in neovascular age-related
      macular degeneration (ARMD). METHODS: Thirty-two patients with active subfoveal
      occult choroidal neovascularisation in ARMD received a single intravitreal
      injection of 1.25 mg bevacizumab and were reinjected based on new or persisting
      subretinal or intraretinal fluid on OCT. Patient visits were every 6-8 weeks.
      RESULTS: After a single injection, 74% of patients demonstrated complete retinal
      fluid absorption, with 44% of patients showing no relapse during a follow-up of
      30+/-13 weeks. Fifty-six percent of patients required a second injection after a
      mean of 19+/-8 weeks, with 82% of patients showing absorption of macular fluid
      thereafter with regain of their previous achieved best-corrected visual acuity.
      Thirty-two percent did not require any further injection (follow-up 32+/-12
      weeks). Of those patients not showing retinal fluid absorption after the first
      injection (26%), 44% demonstrated retinal fluid absorption after the second
      injection. All patients achieved stabilisation of visual acuity during follow-up,
      with 30% of patients showing a significant gain of >or=3 lines. CONCLUSIONS: OCT
      based reinjections of bevacizumab in neovascular ARMD reduce the number of
      injections and lead to anatomic and functional retinal stabilisation.

PMID- 18636266
TI  - [Densiron-68 heavy silicone oil in cases of PVR. Anatomic and functional
      outcomes].
AB  - PURPOSE: To evaluate the safety and efficacy of Densiron-68 heavy silicone oil in
      the clinical management of complex retinal detachments with proliferative
      vitreoretinopathy (PVR). METHODS: We present a prospective, interventional
      noncomparative case series of 80 eyes of 79 consecutive patients. The primary end
      point was anatomical reattachment of the retina, defined as retinal reattachment
      in the absence of any tamponade agent. The secondary end point was to record the
      visual function and surgical complications. Inclusion criteria were PVR stages B
      CA4, including posterior or inferior retinal breaks and the patient's inability
      to posture. RESULTS: Patients were 59.1 (+/-18.1) years old, male:female =48:32,
      R:L=40:40. Fifty-six patients (70%) had previous unsuccessful retinal surgery,
      and 24 (30%) received heavy silicone oil at their first procedure. The extent of
      the detachments was 2.46 quadrants (+/-0.83) with macular involvement in 49 cases
      (61%). Fifty-six (67.5%) patients achieved retinal reattachment with one retinal
      operation and no tamponade, 64 (80%) achieved retinal reattachment with more than
      one operation and no tamponade, and 72 (90%) achieved a flat retina with
      tamponade in situ. Visual acuity rose from 1.48 LogMar (+/-0.91) to 1.12 (+/
      0.82; p=0.009). Densiron was removed after 126 days (+/-55.1). CONCLUSION: The
      treatment of PVR remains challenging. No tamponade agent can provide simultaneous
      support for the superior as well as the inferior retina; therefore, a tamponade
      agent that "sinks" is a welcome new tool for the surgeon. We regard the use of
      heavy as well as conventional silicone oil as complementary to each other.

PMID- 18636268
TI  - Preliminary results in cochlear implant surgery without antromastoidectomy and
      with atraumatic electrode insertion: the endomeatal approach.
AB  - A surgical approach using the external auditory canal and the round window as a
      natural access pathway for cochlear implant positioning, the endomeatal approach,
      is described. This approach avoids performing an antromastoidectomy, the
      subsequent posterior tympanotomy and the promontorial cochleostomy. The
      endomeatal approach also allows an optimal insertion plane for electrode array
      atraumatic insertion through the round window.The technique was developed and
      practiced in 35 fresh temporal bones and then it was applied in ten patients.
      This surgery has an endomeatal first stage, which begins with a stapedectomy-like
      tympanomeatal flap. This flap allows an easy access to scala tympani via round
      window niche. The internal part of a groove is drilled on the posterior wall of
      the EAC. The groove is parallel to the EAC axis and starts in its inner border.
      Once the endomeatal stage is completed, a standard retroauricular approach is
      performed, in order to make the receptor-stimulator well and to complete the
      groove externally, until it connects the middle ear with the external mastoid
      surface. A flat second well is drilled in front of the first one to lodge the
      remaining electrode lead. In small children this well is deepened. The electrode
      array is introduced in the scala tympani through the RW and located into the
      groove. The electrode is covered and fixed inside the groove with bone pate. The
      extra length of the electrode lead is located in the second well and the receptor
      stimulator is fixed in its well. The ground electrode is placed under the
      periosteum, the retroauricular incision is sutured, the tympanomeatal flap is
      restored and a dressing is placed into the EAC. Surgical time was significantly
      shorter than in standard approach. There were neither surgical nor healing
      complications. Electrode insertion was easy and complete and functional results
      were adequate. The goal of this approach is to avoid antromastoidectomy and
      posterior tympanotomy, which are replaced by the EAC groove. It is faster and
      safer, eliminating the risk of facial nerve injury. It also allows a better
      access to the round window, with a less traumatic electrode insertion, suitable
      for "soft surgery" performing. It may advantageously replace the classical
      transmastoideal approach.

PMID- 18636269
TI  - The interplay between propelling efficiency, hydrodynamic position and energy
      cost of front crawl in 8 to 19-year-old swimmers.
AB  - The aim of this study was to investigate the interplay between the arm stroke
      efficiency (an index of propelling efficiency, eta (P)) and the static and
      dynamic position in water (indexes of hydrodynamic resistance, W (d)) in
      determining the energy cost of front crawl (C) during a swimmer's growth. These
      three parameters are indeed related by the following equation:
      C=W(d)/(eta(P).eta(o)) where eta (o) is the overall efficiency of swimming. The
      experiments were carried out on 72 swimmers (38 M and 34 F; 8-19 years) who were
      asked to swim at 1 m s(-1). The static position in water was assessed by
      measuring the underwater torque (T'); the dynamic position in water by measuring
      the projected frontal area (A (eff)). The ratio between the average values of the
      eldest to youngest class of age was 3.84 and 2.27 for T', 2.13 and 1.68 for A
      (eff), and 1.13 and 1.24 for eta (P) (in M and F, respectively). The increase in
      T' and in A (eff) was larger than the increase in efficiency suggesting that, in
      this age range, C should increase, the more so in M than F. Indeed, C increased
      by 1.58 in male and 1.17 in female swimmers. Based on the values of C and eta (P)
      (and assuming a constant value of eta (o)) it is possible to estimate that, in
      this age range, W (d) increases by about 1.97 in male and 1.32 in female
      swimmers, an increase which is proportional to the observed increase in A (eff).

PMID- 18636270
TI  - Immunomodulation of gibberellin biosynthesis using an anti-precursor gibberellin
      antibody confers gibberellin-deficient phenotypes.
AB  - Immunomodulation is a means to modulate an organism's function by antibody
      production to capture either endogenous or exogenous antigens. We have recently
      succeeded in obtaining gibberellin (GA)-deficient phenotypes in Arabidopsis
      thaliana by using anti-bioactive GA antibodies. In this study, a single-chain
      antibody (scFv) against GA(24), a precursor GA, was utilized to repress the
      biosynthesis of bioactive gibberellins. Stable accumulation of the scFv in
      endoplasmic reticulum (ER) was achieved by being produced as a fusion with GFP as
      well as KDEL ER-retention signal. The transgenic plants showed GFP fluorescence
      in the reticulate cortical ER network in epidermal cells. The GFP-scFv fusion
      produced in plants maintained its binding activity. The transgenic plants showed
      GA-deficient phenotypes, including reduced rosette leaf development, delayed
      flower induction and reduced stem elongation of the main culm, especially in the
      early stage of inflorescence growth. Contrarily, stem elongation of the main culm
      at a later stage, or that of lateral shoots was much less affected by scFv
      production. These phenotypes were different from anti-bioactive GA scFv-producing
      lines, whose stem elongation was continuously repressed throughout the
      inflorescence development. The GA-deficient phenotypes were recovered by
      treatment with GA(24) and bioactive GA(4), the latter being more effective. The
      transgenic lines contained conspicuously higher endogenous GA(24) and clearly
      less GA(4) than wild-type plants. The expression of GA 20-oxidase and GA 3
      oxidase genes, which are feedback-regulated by GA signaling, were up-regulated in
      those plants. These results demonstrate that the scFv trapped GA(24) in ER and
      inhibited metabolism of GA(24) to bioactive GA(4).

PMID- 18636271
TI  - Differential effects of severe water stress on linear and cyclic electron fluxes
      through Photosystem I in spinach leaf discs in CO(2)-enriched air.
AB  - Linear and cyclic electron fluxes through Photosystem I in 1% CO(2) were
      quantified in spinach leaf tissue under severe water stress. Using actinic light
      with a peak at 697 nm for preferential light absorption by Photosystem I while
      also stimulating Photosystem II to improve redox poising, the cyclic electron
      flux after 60 s of illumination was a substantial proportion (33-44%) of the
      total electron flux through PSI at irradiances up to ~1,070 micromol photons m(
      2) s(-1). At the maximum irradiance, the cyclic electron flux changed little with
      the progressive water loss from leaf tissue up to ~60%; by contrast, the linear
      electron flux was approximately halved. A reason for this differential effect of
      water stress on the capacity for cyclic and linear electron flow could be the
      increased crowding of soluble proteins in the stroma due to chloroplast
      shrinkage. Indeed the confinement of soluble proteins to a smaller chloroplast
      volume was indicated by cryo-scanning electron microscopy. It is known that the
      diffusion coefficient of large proteins is decreased when the background
      concentration of small proteins is raised; by contrast, the diffusion coefficient
      of small proteins is not affected by increasing the concentration of a large
      protein (Muramatsu and Minton in Proc Natl Acad Sci USA 85:2984-2988, 1988).
      Therefore, we suggest that linear electron flow, being coupled to the Calvin
      Benson cycle, is limited by the diffusion of large macromolecules, especially the
      ribulose 1, 5-bisphosphate carboxylase/oxygenase complex. By contrast, cyclic
      electron flow, involving relatively small macromolecules such as ferredoxin, is
      less susceptible to inhibition by crowding in the stroma.

PMID- 18636272
TI  - Emotional Stroop task: effect of word arousal and subject anxiety on emotional
      interference.
AB  - Inconsistent findings regarding the emotional Stroop effect in healthy subjects
      may be explained by confounding effects of stimulus valence and arousal, as well
      as individual differences in anxiety. We examined reaction time data in a healthy
      sample using the emotional Stroop task while carefully matching arousal level of
      positive and negative words. Independent of valence, emotional relative to
      neutral words elicited emotional interference, indicating that arousal determines
      emotional interference. Independent of valence, emotional words were better re
      called and recognized than neutral words. Individual differences in state anxiety
      were associated with emotional interference, that is, emotional interference was
      enhanced in subjects with high state anxiety. There was no influence of trait
      anxiety. These findings indicate that word arousal produces emotional
      interference independent of valence. State anxiety exacerbates interference of
      emotional words by further biasing attention towards emotionally salient stimuli.

PMID- 18636273
TI  - Systemic EBV+ T-cell lymphoma in elderly patients: comparison with children and
      young adult patients.
AB  - Fulminant Epstein-Barr virus (EBV+) T-cell lymphoma in immunocompetent elderly
      patients is rare and its character has not been well defined. This study analyzed
      the clinicopathological features of five elderly patients (group A: 50-84 years)
      and compared them with those of eight children and young adult patients with
      systemic T-cell lymphomas (group B: 10-34 years). Group A more commonly presented
      with generalized lymphadenopathy (n = 3) than did group B (n = 1). Chronic active
      EBV infection (n = 3) and hydroa vacciniforme-like eruptions (n = 1) were seen in
      group B, while group A showed no evidence of chronic EBV infection, but did show
      chronic hepatitis B or C virus infections (n = 3). The histological and
      immunophenotypical findings were similar. All patients died within 1 to 14 months
      of diagnosis. These findings suggest that EBV+ T-cell lymphoma in elderly
      patients is a unique disease with an underlying derangement of T-cell immunity
      and failure to eradicate infected virus. Additional factors related to senility
      may play a role in the disruption of homeostasis between the virus and the host's
      immune system.

PMID- 18636274
TI  - Environmental factors affecting children's respiratory health in the first years
      of life: a review of the scientific literature.
AB  - The aim of this paper is to quantitatively summarize the original articles on the
      relationship between environmental hazards and respiratory health in young
      children. A search was carried out in the main biomedical bibliographical sources
      in December 2006 and then the results were updated in June 2007. The study period
      covered 11 years (1996-2006). The information was assessed by reviewing the
      abstracts. Six hundred and forty documents were recovered. Documents from the
      United States accounted for 23.5% of articles. The production tended to increase
      over the study period. The factor most widely studied was air pollution, with
      outdoor air pollution being studied more (just over 50% of articles) than indoor
      air pollution (40%). Asthma was the most often studied condition (75% of
      articles). In a third of the cases, the information was obtained from hospital or
      health center records, and in 20% from questionnaires. The main diagnostic
      criterion was clinical. Infection of the inferior respiratory tracts predominated
      in children less than 3 years of age. An awareness of the role played by
      pollution and environmental hazards is fundamental in the management and
      prevention of respiratory problems in childhood, and this is reflected in the
      literature reviewed. However, very few synthesis studies have been carried out on
      this matter.

PMID- 18636275
TI  - Expression of Indian Hedgehog signaling molecules in breast cancer.
AB  - PURPOSE: To investigate the clinicopathological significance and expression
      pattern of Hedgehog (Hh) signaling molecules in breast normal glands and invasive
      ductal carcinoma. MATERIALS AND METHODS: A total of 142 cases, including 21 of
      normal breast and 121 of invasive ductal carcinoma of the breast, were
      immunohistochemically analyzed for Ihh, Ptch, Smo, Gli-1, Gli-2, and Gli-3
      protein expression. RESULTS: All of Hh signaling molecules were greatly enhanced
      in invasive ductal carcinoma compared with the normal breast epithelia. The
      expressions of Ihh, Smo, and Gli-2 were increased in PR negative cases, and the
      expressions of Ihh, Ptch, and Gli-1/2/3 were statistically correlated with
      increased proliferating index of Ki-67 in invasive ductal carcinoma. Ihh and Gli
      1/2/3 expressions were correlated with node metastasis. Additionally, the protein
      expressions of Ihh, Ptch, and Gli-2 were correlated with the clinical stage of
      breast cancer. CONCLUSIONS: Hedgehog signaling molecules play an important role
      in the progression of invasive ductal carcinoma of breast.

PMID- 18636276
TI  - Diversity of LTR-retrotransposons and Enhancer/Suppressor Mutator-like
      transposons in cassava (Manihot esculenta Crantz).
AB  - Cassava (Manihot esculenta Crantz), though a major world crop with enormous
      potential, is very under studied. Little is known about its genome structure and
      organisation. Transposable elements have a key role in the evolution of genome
      structure, and can be used as important tools in applied genetics. This paper
      sets out to survey the diversity of members of three major classes of
      transposable element within the cassava genome and in relation to similar
      elements in other plants. Members of two classes of LTR-retrotransposons,
      Ty1/copia-like and Ty3/gypsy-like, and of Enhancer/Suppressor Mutator (En/Spm)
      like transposons were isolated and characterised. Analyses revealed 59 families
      of Ty1/copia, 26 families of Ty3/gypsy retrotransposons, and 40 families of
      En/Spm in the cassava genome. In the comparative analyses, the predicted amino
      acid sequences for these transposon classes were compared with those of related
      elements from other plant species. These revealed that there were multiple
      lineages of Ty1/copia-like retrotransposons in the genome of cassava and
      suggested that vertical and horizontal transmission as the source of cassava
      Mecops may not be mutually exclusive. For the Ty3/gypsy elements network, two
      groups of cassava Megyps were evident including the Arabidopsis Athila lineage.
      However, cassava En/Spm-like elements (Meens) constituted a single group within a
      network of plant En/Spm-like elements. Hybridisation analysis supported the
      presence of transposons in the genome of cassava in medium (Ty3/gypsy and En/Spm)
      to high (Ty1/copia) copy numbers. Thus the cassava genome was shown to contain
      diverse members of three major classes of transposable element; however, the
      different classes exhibited contrasting evolutionary histories.

PMID- 18636277
TI  - Trophic cascades initiated by fungal plant endosymbionts impair reproductive
      performance of parasitoids in the second generation.
AB  - Variation in plant quality can transmit up the food chain and may affect
      herbivores and their antagonists in the same direction. Fungal endosymbionts of
      grasses change the resource quality by producing toxins. We used an aphid
      parasitoid model system to explore how endophyte effects cascade up the food
      chain and influence individual parasitoid performance. We show that the presence
      of an endophyte in the grass Lolium perenne has a much stronger negative impact
      on the performance of the parasitoid Aphidius ervi than on its aphid host
      Metopolophium festucae. Although the presence of endophytes did not influence the
      parasitism rate of endophyte-naive parasitoids or their offspring's survival to
      adulthood, most parasitoids developing within aphids from endophyte-infected
      plants did not reproduce at all. This indicates a delayed but very strong effect
      of endophytes on parasitoid performance, which should ultimately affect plant
      performance negatively by releasing endophyte-tolerant herbivores from top-down
      limitations.

PMID- 18636278
TI  - Peritoneal membrane recruitment in rats: a micro-computerized tomography (muCT)
      study.
AB  - The peritoneal contact surface area (PCSA), which represents the area parameter
      in the mass transfer area coefficient (MTAC), is a crucial marker in the
      evaluation of peritoneal dialysis effectiveness. However, the capacity to recruit
      a larger PCSA has only been rarely demonstrated in vivo and, in most cases,
      changes in MTAC are interpreted as permeability changes and not as surface area
      variations. Here, we report the use of micro-computerized tomography (muCT) for
      the measurement of PCSA changes to various fill volumes. Using this three
      dimensional imaging method, PCSA was measured in vivo in 26 healthy Wistar rats
      receiving intraperitoneally increasing fill volumes of peritoneal dialysis
      solutions: 5 mL (group 1, n = 8), 10 mL (group 2, n = 8) and 15 mL (group 3, n =
      10) per 100 g of body weight. A non-ionic iodinated contrast agent was added to
      the dialysis solution in order to distinguish the intraperitoneal dialysis
      solutions from soft tissues. The normalized PCSA/weight ratio (cm(2)/g) increased
      with fill volume: 1.12 +/- 0.10 cm(2)/g (range 0.98-1.25) in group 1; 1.74 +/-
      0.08 cm(2)/g (range 1.64-1.87) in group 2; 2.13 +/- 0.09 cm(2)/g(range 1.90-2.30)
      in group 3. With this muCT method, PCSA recruited in vivo with a 10 mL/100 g fill
      volume was in the range 94-107%) of ex vivo total peritoneal surface area
      (evPSA), as calculated with the Kuzlan's formula. With a 15 mL/100 g fill volume,
      the in vivo-measured PCSA, the exchange surface area, surpassed the evPSA (range
      113-139%).

PMID- 18636279
TI  - [Peridural application of ropivacaine and clonidine for pain therapy after
      prostatectomy].
AB  - OBJECTIVE: The aim of this study was to find out if ropivacaine with clonidine
      can be successfully used after radical retropubic prostatectomy. MATERIAL AND
      METHODS: A total of 86 patients were randomized into two groups each consisting
      of 43 patients. Patients in group 1 received epidural
      bupivacaine/morphine/clonidine and those in group 2 ropivacaine and clonidine. If
      necessary analgesic, antiemetic or antihistamine drugs were administered. Pain on
      a visual analogue scale (VAS), motoric and sensoric disturbances, sedation,
      itching, nausea and vomiting, hypotension, need of antihistamines, naloxon,
      antiemetics, ephedrine, and analgesics were also documented. RESULTS: Differences
      in sedation, itching, nausea and vomiting, motoric and sensoric disturbances,
      need of antihistamines, antiemetics, and ketoprofen were significant, the other
      parameters did not show any significant differences. CONCLUSIONS: We recommend
      the use of ropivacaine with clonidine in the postoperative pain management after
      radical retropubic prostatectomy.

PMID- 18636280
TI  - Cost-effectiveness of percutaneous vertebroplasty in osteoporotic vertebral
      fractures.
AB  - A retrospective study was conducted in 179 consecutive patients (48 males, 131
      females; mean age: 72.0 +/- 8.59 years; range: 51-93) with single symptomatic
      acute amyelic osteoporotic vertebral fracture presenting between September 2004
      and September 2005 to the Santa Lucia Foundation in Rome, Italy. Vertebral
      fractures usually become manifest due to pain which can be debilitating.
      Treatment depends on the presence or absence of spinal cord involvement. In the
      first case, surgical stabilization is mandatory. In the second case, treatment
      may be performed either by conservative medical therapy (CMT) or percutaneous
      vertebroplasty (PVT). The aim of this study was to evaluate the effectiveness,
      costs and cost-effectiveness of percutaneous vertebroplasty. After 2 weeks of
      analgesic therapy, 153 patients presented refractory pain and were offered
      treatment by PVT. A total of 58 patients accepted and underwent PVT (PVT group),
      while 95 refused and underwent conservative medical therapy (CMT group). Follow
      up was performed by specialist consults, spine radiography and MRI and a self
      assessment questionnaire evaluating pain using a Visual Analogue Scale (VAS) and
      function using an ambulation and an Activities of Daily Living (ADL) scale. A 12
      month follow-up was obtained in 86 of 95 (90.5%) CMT group patients and 54 of 58
      (93.1%) PVT group patients. Significant reduction of VAS and improvement of
      ambulation and ADL was observed in both groups at 1 week and 3 and 12 months (P <
      0.05; Wilcoxon signed rank test), however, these results were significantly
      superior in the PVT group at 1 week and 3 months (P < 0.05; Mann-Whitney U test).
      Average cost per patient at 1 week and 3 and 12 months were respectively 755.49
      +/- 661.96, 3791.95 +/- 3341.97 and 4299.55 +/- 3211.53 euros (CMT group) and
      3311.35 +/- 0.32, 3745.30 +/- 3.59 and 4101.05 +/- 755.41 euros (PVT group). PVT
      resulted significantly more cost-effective than CMT with regards to the three
      scales at 1 week (P < 0.05; Mann-Whitney U test). At 3 months PVT was more cost
      effective than CMT with regards to the three scales, however, the difference was
      significant only with regards to ambulation. No significant differences in cost
      effectiveness where found between the two groups at 12 months. PVT should be
      considered the treatment of first choice in symptomatic acute amyelic
      osteoporotic vertebral fractures with refractory pain after a short period of
      analgesic therapy.

PMID- 18636281
TI  - Three-dimensional reconstruction after removal of zygomatic intraosseous
      hemangioma.
AB  - INTRODUCTION: Intraosseous hemangioma, especially in the zygomatic area, is a
      very rare pathologic condition among the osseous tumors of the head and neck
      area. Clinical presentation includes a painless mass with progressive growth and
      hard consistence. Diagnosis is performed by means of computed tomography (CT).
      Treatment includes radical en bloc surgical excision with healthy bone margins in
      order to avoid blood loss. Previous embolization is not necessary. Bony defect
      reconstruction must be performed to avoid secondary deformities. CASE REPORT: We
      present a case report of a 30-year-old female presenting a progressive painless
      swelling in the malar and zygomatic regions. CT scan demonstrated a right
      zygomatic lesion that extended into the orbital floor and lateral orbital wall,
      affecting also the zygomatic arch. The biopsy revealed an intraosseous
      hemangioma. Treatment was performed including an en bloc resection with healthy
      bony margins and primary reconstruction with calvarian bone graft in association
      with galea-pericranium flap.

PMID- 18636282
TI  - Mule cognition: a case of hybrid vigour?
AB  - This study compares the behaviour of the mule (Equus asinus x Equus caballus)
      with that of its parent species to assess the effects of hybridization on
      cognition. Six mules, six ponies (E. caballus) and six donkeys (E. asinus) were
      given a two choice visual discrimination learning task. Each session consisted of
      12 trials and pass level was reached when subjects chose the correct stimulus for
      at least 9 out of the 12 trials in three consecutive sessions. A record was made
      of how many pairs each subject learnt over 25 sessions. The mules' performance
      was significantly better than that of either of the parent species (Kruskal
      Wallis: H(x) = 8.11, P = 0.017). They were also the only group to learn enough
      pairs to be able to show a successive reduction in the number of sessions
      required to reach criterion level. This study provides the first empirical
      evidence that the improved characteristics of mules may be extended from physical
      attributes to cognitive function.

PMID- 18636286
TI  - Size-dependent denaturing kinetics of bovine serum albumin adsorbed onto gold
      nanospheres.
AB  - We have used localized surface plasmon resonance (LSPR) to monitor the kinetics
      of thermal denaturing of bovine serum albumin (BSA) adsorbed onto gold
      nanospheres of size 5 nm-100 nm. The effect of the protein on the LSPR was
      monitored by visible extinction spectroscopy. The wavelength of the peak
      extinction (resonance) is affected by the conformation of the adsorbed protein
      layer, and as such can be used as a very sensitive probe of thermal denaturing
      that is specific to the adsorbed (as opposed to free) protein. The time
      dependence of the denaturing is measured in the temperature range 60 degrees C-70
      degrees C, and the lifetimes are used to calculate an activation barrier for
      thermal denaturing. The results show that thermally activated denaturing of
      proteins adsorbed onto nanoparticles has a nanoparticle-size-dependent activation
      barrier, and this barrier increases for decreasing particle size. This may have
      important implications for other protein-nanoparticle interactions.

PMID- 18636287
TI  - An improved method for separating cardiolipin by HPLC.
AB  - Herein we report an improved method to separate cardiolipin (Ptd(2)Gro) from
      tissue total lipid extracts using a biphasic solvent system combined with high
      performance liquid chromatography. This method uses a normal phase silica column
      and two mobile phases: mobile phase A that was n-hexane:2-propanol (3:2 by vol)
      and mobile phase B that was n-hexane:2-propanol:water (56.7:37.8:5.5 by vol). The
      initial solvent conditions were 95% A and 5% B, with a flow rate of 1.5 mL/min.
      The samples were from non-derivatized aliquots of liver, heart, or brain lipid
      extracts. The peak corresponding to Ptd(2)Gro appeared at 31 min, was well
      defined and did not overlap with neighboring peaks. The adjacent peak
      corresponded to ethanolamine glycerophospholipids and the remaining phospholipids
      were eluted in a single peak. The identity of the phospholipids separated by this
      method was verified by thin layer chromatography (TLC) and fatty acid analysis,
      which confirmed that the Ptd(2)Gro was well resolved from other phospholipids.
      This method is useful to separate and quantify Ptd(2)Gro from small tissue
      samples thereby avoiding the variability associated with TLC methods.

PMID- 18636289
TI  - Dialysis shunt-associated steal syndrome with autogenous hemodialysis accesses:
      proposal for a new classification based on clinical results.
AB  - BACKGROUND: Dialysis-associated steal syndrome (DASS) is a multifactorial
      complication. There are several therapeutic options, although because of the lack
      of research decisions for certain procedures are often made individually. The aim
      of this retrospective survey was to propose a new classification for DASS,
      including therapeutic recommendations, to make standardized procedures easier.
      METHODS: A total of 63 patients (2001-2006) treated for DASS following
      autogenuous hemodialysis access (HA) were included in this survey. In 55 (87%) of
      these patients, surgery was performed. The courses of disease of the patients
      were evaluated according to clinical symptoms, HA-specific features, and
      therapeutic results. Statistical evaluation was performed by SSPS software.
      RESULTS: Eight patients with mild symptoms were treated successfully using
      conservative therapy. In 17 patients with pain during exercise or acute
      neurologic deficiencies, HA banding led to good results. In the case of acral
      lesions, however, banding was unsuccessful, although interruption of the
      retrograde flow was sufficient therapy in 94% of cases. Preservation of the HA
      was unsuccessful in all patients with extended tissue loss (n = 10). Statistical
      evaluation showed that tissue loss was generally associated with diabetes (p <
      0.001) and peripheral arterial occlusive disease (p = 0.001). CONCLUSION: In
      addition to steal phenomenon (stage I), which can be treated conservatively,
      there are three stages of DASS following autogenuous HA that require surgical
      intervention (stage II, no acral lesions; stage III, small acral lesions; stage
      IV, extended acral lesions). HA banding leads to good results in stage II; in
      patients with stage III, interruption of the retrograde flow is indicated.
      However, in patients with extensive tissue loss (stage IV), closure of the HA
      should be considered.

PMID- 18636290
TI  - Cancer-associated genomic regions (CAGRs) and noncoding RNAs: bioinformatics and
      therapeutic implications.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs, RNAs that do not code for
      proteins) that regulate the expression of target genes at the posttranscriptional
      or posttranslational level. Many miRNAs have conserved sequences between
      distantly related organisms, suggesting that these molecules participate in
      essential developmental and physiologic processes. miRNAs can act as tumor
      suppressor genes or oncogenes in human cancers. Mutations, deletions, or
      amplifications have been found in human cancers and shown to alter expression
      levels of mature and/or precursor miRNA transcripts. Moreover, a large fraction
      of genomic ultraconserved regions (UCRs) encode a particular set of ncRNAs whose
      expression is altered in human cancers. Both miRNAs and UCRs are frequently
      located at fragile sites and genomic regions affected in various cancers, named
      cancer-associated genomic regions (CAGRs). Bioinformatics studies are emerging as
      important tools to identify associations and/or correlations between
      miRNAs/ncRNAs and CAGRs. ncRNA profiling has allowed the identification of
      specific signatures associated with diagnosis, prognosis, and response to
      treatment of human tumors. Several abnormalities could contribute to the
      alteration of miRNA expression profiles in each kind of tumor and in each kind of
      tissue. This review is focused on the miRNAs and ncRNAs as genes affecting cancer
      risk, and we provided an updated catalog of miRNAs and UCRs located at fragile
      sites or at cancer susceptibility loci. These types of studies are the first step
      toward discoveries leading to novel approaches for cancer therapies.

PMID- 18636291
TI  - Natural orifice transesophageal mediastinoscopy and thoracoscopy: a survival
      series in swine.
AB  - INTRODUCTION: Transesophageal endoscopic mediastinoscopy (MX) and thoracoscopy
      (TX) could reduce pain, eliminate intercostal neuralgia, provide better access to
      the posterior mediastinal compartment and pulmonary hilum, and improve cosmesis.
      The purpose of this study was to demonstrate the feasibility of transesophageal
      natural orifice translumenal endoscopic surgery (NOTES) and to determine the
      complications that might be seen in surviving animals. METHODS: Using cap
      endoscopic mucosal resection and blunt dissection, a 15-20 cm submucosal tunnel
      was created in the esophagus and an endoscope passed through the tunnel into the
      mediastinum. One swine underwent MX; three swine underwent both MX and TX. The
      mediastinal compartment, hilar lymph nodes, pleura, lung, and esophagus were
      identified. Esophageal closure was obtained via submucosal tunnel flap-valve
      alone (two swine) or reinforcement with mucosal clips (two swine). The esophagus,
      mediastinum, and thorax were examined at necropsy. The esophagus was excised and
      sent for pathological examination. RESULTS: NOTES MX and TX provided excellent
      visualization of mediastinal and thoracic structures. Pleural biopsy was easily
      accomplished. All animals survived the procedure, ate well, and showed no ill
      effects. Swine were sacrificed at either 8 or 12 days postoperatively. At
      necropsy, mild atelectasis was noted in each animal. One animal (mucosal clip
      closure) developed a fluid collection in the submucosal tunnel. There was no
      evidence of mediastinitis or thoracic contamination in any animals. CONCLUSIONS:
      Transesophageal endoscopic mediastinoscopy and thoracoscopy provide excellent
      visualization of mediastinal and intrathoracic structures. Pleural biopsy can be
      easily obtained under direct visualization. Structures that are difficult to
      visualize via traditional cervical mediastinoscopy and thoracoscopy are seen well
      with this approach. The submucosal tunnel creates a flap-valve that, alone, may
      be sufficient for preventing esophageal leak. These procedures can be performed
      safely in swine with short-term survival. Further study with a larger sample size
      and longer survival is warranted.

PMID- 18636292
TI  - Requirements for the design and implementation of checklists for surgical
      processes.
AB  - BACKGROUND: The use of checklists is a promising strategy for improving patient
      safety in all types of surgical processes inside and outside the operating room.
      This article aims to provide requirements and implementation of checklists for
      surgical processes. METHODS: The literature on checklist use in the operating
      room was reviewed based on research using Medline, Pubmed, and Google Scholar.
      Although all the studies showed positive effects and important benefits such as
      improved team cohesion, improved awareness of safety issues, and reduction of
      errors, their number still is limited. The motivation of team members is
      considered essential for compliance. Currently, no general guidelines exist for
      checklist design in the surgical field. Based on the authors' experiences and on
      guidelines used in the aviation industry, requirements for the checklist design
      are proposed. The design depends on the checklist purpose, philosophy, and method
      chosen. The methods consist of the "call-do-response" approach," the "do-verify"
      approach, or a combination of both. The advantages and disadvantages of paper
      versus electronic solutions are discussed. Furthermore, a step-by-step strategy
      of how to implement a checklist in the clinical situation is suggested.
      CONCLUSIONS: The use of structured checklists in surgical processes is most
      likely to be effective because it standardizes human performance and ensures that
      procedures are followed correctly instead of relying on human memory alone.
      Several studies present promising and positive first results, providing a solid
      basis for further investigation. Future research should focus on the effect of
      various checklist designs and strategies to ensure maximal compliance.

PMID- 18636293
TI  - Technical enhancements to breast ductal lavage.
AB  - BACKGROUND: Ductal lavage is a technique that samples the contents of breast
      ducts for research into the biology of breast cancer. Enthusiasm for this method
      has declined because of technical challenges associated with the procedure. These
      include: difficulty in duct cannulation, high levels of subject discomfort, and
      an inability to confirm perforation. METHODS: As part of a larger institutional
      review board (IRB)-approved study, consenting healthy women underwent ductal
      lavage of 3-4 ducts in one breast. Intranipple lidocaine was administered before
      duct cannulation. Ductoscopy was performed prior to catheterization and high
      definition ultrasound was used for imaging during the lavage procedure. Pain
      scores were recorded at 24 hours and 2 weeks. Subjects were asked to return in 6
      months for a repeat of the procedure. RESULTS: Ductoscopy was performed prior to
      lavage under real-time ultrasound 308 times in 107 subjects. There were 280
      confirmed ducts (90.9%) and 21 perforations (6.8%), while seven (2.3%) were
      indeterminate. Subjects reported minimal discomfort, and 91% reported a 0 (0-10
      range) pain score 2 weeks after the procedure. The retention rate was 90% at 6
      months. CONCLUSION: The injection of lidocaine directly into the nipple greatly
      increases the feasibility of duct cannulation and improves subject comfort.
      Confirmation of duct cannulation and lavage can be documented with ductoscopy and
      ultrasound imaging. These procedures can be added to ductal lavage to facilitate
      its use as a research tool.

PMID- 18636294
TI  - Lymph node status influences follow-up thyroglobulin levels in papillary thyroid
      cancer.
AB  - BACKGROUND: Elevated thyroglobulin (Tg) levels post surgery are associated with
      disease recurrence in papillary thyroid carcinoma (PTC). The aim of this study is
      to determine which clinicopathological factors influence Tg elevation following
      surgery and radio-iodine ablation (RAI) for PTC. METHODS: A retrospective study
      of consecutive patients undergoing total thyroidectomy and RAI for PTC was
      carried out. Prophylactic central neck dissection (CND) was performed if the
      diagnosis of PTC was made preoperatively. Lateral neck dissection (LND) was
      guided by ultrasound findings. RAI was administered 6 weeks postoperatively.
      Stimulated Tg levels were measured at 12 months. RESULTS: One hundred patients
      with PTC were studied. Forty patients had routine CND. The median tumour size was
      15 mm. Median stimulated Tg level at 12 months was 0.3 mug/L. On multivariate
      analysis the number of metastatic lymph nodes removed had a significant positive
      association with serum Tg levels (P = 0.003). The total number of lymph nodes
      resected had a significant inverse relationship with serum Tg levels (P = 0.04).
      Tumour size, multifocality, vascular and capsular invasion did not appear to have
      significant correlation with Tg levels. CONCLUSION: Lymph node metastases are
      associated with increased postablative Tg levels in PTC. More complete
      lymphadenectomy is associated with lowering of Tg levels.

PMID- 18636295
TI  - Use of Gliadel (BCNU) wafer in the surgical treatment of malignant glioma: a 10
      year institutional experience.
AB  - BACKGROUND: Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly
      used for local delivery of BCNU to high-grade gliomas after resection and is
      associated with increased survival. Various complications of Gliadel wafers have
      been reported but not consistently reproduced. We set out to characterize Gliadel
      associated morbidity in our 10-year experience with Gliadel wafers for treatment
      of malignant glioma. METHODS: We retrospectively reviewed records of 1013
      patients undergoing craniotomy for resection of malignant brain astrocytoma
      (World Health Organization grade III/IV disease). Perioperative morbidity
      occurring within 3 months of surgery was assessed for patients and compared
      between patients receiving versus not receiving Gliadel wafer. Overall survival
      was assessed for all patients. RESULTS: A total of 1013 craniotomies were
      performed for malignant brain astrocytoma. A total of 288 (28%) received Gliadel
      wafer (250 glioblastoma multiforme (GBM), 38 anaplastic astrocytoma/anaplastic
      oligodendroglioma (AA/AO), 166 primary resection, 122 revision resection).
      Compared with the non-Gliadel cohort, patients receiving Gliadel were older (55
      +/- 14 vs. 50 +/- 17, P = .001) and more frequently underwent gross total
      resection (75% vs 36%, P < .01) but otherwise similar. Patients in Gliadel versus
      non-Gliadel cohorts had similar incidences of perioperative surgical site
      infection (2.8% vs. 1.8%, P = .33), cerebrospinal fluid leak (2.8% vs. 1.8%, P =
      .33), meninigitis (.3% vs. .3%, P = 1.00), incisional wound healing difficulty
      (.7% vs. .4%, P = .63), symptomatic malignant edema (2.1% vs. 2.3%, P = 1.00), 3
      month seizure incidence (14.6% vs. 15.7%, P = .65), deep-vein thrombosis (6.3%
      vs. 5.2%, P = .53), and pulmonary embolism (PE) (4.9% vs. 3.7%, P = .41). For
      patients receiving Gliadel for GBM, median survival was 13.5 months after primary
      resection (20% alive at 2 years) and 11.3 months after revision resection (13%
      alive at 2 years). For patients receiving Gliadel for AA/AO, median survival was
      57 months after primary resection (66% alive at 2 years) and 23.6 months after
      revision resection (47% alive at 2 years). CONCLUSION: In our experience, use of
      Gliadel wafer was not associated with an increase in perioperative morbidity
      after surgical treatment of malignant astrocytoma.

PMID- 18636296
TI  - Chemotherapy with bevacizumab does not affect liver regeneration after portal
      vein embolization in the treatment of colorectal liver metastases.
AB  - BACKGROUND: Blockage of vascular endothelial growth factor (VEGF) in murine
      models has been shown to impair liver regeneration after partial hepatectomy. The
      aim of this study was to evaluate the effects of chemotherapy with or without
      bevacizumab (monoclonal antibody anti-VEGF) on liver regeneration after portal
      vein embolization (PVE) in the treatment of colorectal liver metastases and its
      possible effect on postoperative outcome after major liver resection. METHODS:
      Records of 65 consecutive patients treated with or without preoperative
      chemotherapy (with or without bevacizumab) and PVE for colorectal liver
      metastases from September 1995 to February 2007 were reviewed from a prospective
      database. Future liver remnant (FLR) volume, degree of FLR hypertrophy after PVE,
      morbidity, mortality, and survival were analyzed. RESULTS: Preoperative PVE was
      performed after chemotherapy in 43 patients and without chemotherapy in 22
      patients. Among the 43 patients treated with chemotherapy, 26 received concurrent
      bevacizumab. After a median of 4 weeks after PVE, there was no difference in FLR
      volume increase among patients treated with or without chemotherapy. Similarly,
      there was no statistically significant difference in degree of FLR hypertrophy
      among patients treated without (mean, 10.1%) or with chemotherapy, with or
      without bevacizumab (8.8% and 6.8%) (P = .11). Forty-eight (74%) of 65 patients
      underwent extended right or right hepatectomy after PVE. No differences in
      morbidity and mortality were observed among patients treated with or without
      preoperative chemotherapy (with or without bevacizumab). CONCLUSION: Preoperative
      chemotherapy with bevacizumab does not impair liver regeneration after PVE. Liver
      resection can be performed safely in patients treated with bevacizumab before
      PVE.

PMID- 18636297
TI  - A single question may be useful for detecting patients with inadequate health
      literacy.

PMID- 18636298
TI  - Timing of cholecystectomy for biliary pancreatitis: do the data support current
      guidelines?
AB  - BACKGROUND: Current guidelines suggest that cholecystectomy be performed within 2
      weeks after discharge following an episode of biliary pancreatitis. We
      hypothesized that a high incidence of gallstone-related events is present within
      2 weeks after discharge prior to cholecystectomy. METHODS: Two hundred eighty-one
      patients who underwent cholecystectomy for biliary pancreatitis (January 1999
      December 2005) were categorized into one of two groups: group A patients
      underwent cholecystectomy during index admission (n = 162), and group B patients
      underwent cholecystectomy following discharge from index admission (n = 119).
      RESULTS: Groups were comparable in demographics, comorbidities, and disease
      severity. Thirty-nine (32.8%) group B patients experienced pre-cholecystectomy
      gallstone-related events (including 16 cases of recurrent pancreatitis) after
      discharge. Recurrences (31.3%) occurred within 2 weeks after discharge.
      Endoscopic sphincterotomy protected against preoperative recurrent pancreatitis
      but was associated with a higher incidence of other gallstone-related events.
      Median total length of hospital stay was greater for group B than for group A [7
      (range, 2-37) days vs. 5 (1-45) days, respectively, p = 0.00]. CONCLUSION:
      Current guidelines suggesting the appropriateness of waiting up to 2 weeks for
      cholecystectomy for biliary pancreatitis may place patients at unacceptably high
      risk for recurrence. Endoscopic sphincterotomy does not eliminate the risk of
      gallstone-related events.

PMID- 18636299
TI  - Surgical treatment concepts for acute lower gastrointestinal bleeding.
AB  - BACKGROUND AND PURPOSE: To this day, the diagnostic and therapeutic strategy for
      acute lower gastrointestinal hemorrhage requiring transfusion varies among
      different hospitals. The purpose of this paper was to evaluate our own data on
      the group of patients presented and to outline our diagnostic and therapeutic
      regime taking into account the literature of the past 30 years. METHODS:
      Following prospective data collection on 63 patients of a university hospital (40
      male, 23 female patients) who received surgical intervention for acute lower
      intestinal hemorrhage requiring transfusion, we retrospectively analyzed the
      data. After a medical history had been taken, all patients underwent clinical
      examination, including digital palpation; 62 patients underwent procto
      rectoscopy, 38 gastroscopy and colonoscopy, 52 patients colonoscopy only, and 45
      patients gastroscopy only. Angiography was applied in 14 cases and scintigraphy
      in 20 cases. RESULTS: Diagnostic procedures to localize hemorrhage were
      successful in 61 cases, 41 of which through endoscopy, 12 through angiography,
      and eight through scintigraphy. Of our group of patients, 32 suffered from a
      bleeding colonic diverticulum, eight from angiodysplasia, and five from bleeding
      small bowel diverticula. Five patients had inflammatory bowel disease and three
      neoplasia. Among the surgical interventions, segmental resections were performed
      most frequently (15 sigmoidectomies, 11 small bowel segmental resections, 11 left
      hemicolectomies, seven right hemicolectomies, one proctectomy). Subtotal
      colectomies were carried out in ten cases. The complication rate for this group
      of critically ill, negatively selected patients was 60.3% and the mortality rate
      was 15.9%. CONCLUSIONS: Examination and stabilization of the patient is directly
      followed by diagnostic localization. Today, we primarily rely on nonsurgical
      control of hemorrhage by endoscopy or angiography; the indication for surgery is
      mainly limited to peracute, uncontrollable, and recurrent forms. In the case of
      surgery, intestinal segmental resection is recommended after identification of
      the lesion; if the localization of colonic hemorrhage is uncertain, subtotal
      resection is the method of choice. For stable patients with unverifiable small
      bowel hemorrhage we recommend regular re-evaluation.

PMID- 18636300
TI  - How can we control intraoperative bacterial contamination and surgical-site
      infection during an anterior resection or Hartmann's/Miles' operation?
AB  - PURPOSE: Intraoperative bacterial contamination (IBC) is a major cause of
      surgical-site infection (SSI). Therefore, we investigated whether the ingenuity
      of surgical procedures could reduce the incidence of IBC/SSI. METHODS: Sixty
      patients who were surgically treated for recto-sigmoid cancer were investigated.
      Among these patients, the colon was transected during the early perioperative
      period (ET) in 29 patients and during the late period (LT) in 31 patients. Three
      samples for IBC were obtained from the irrigation fluid before abdominal closure
      (LAVAGE), the remaining cut sutures after peritoneal closure (SUTURE), and a
      subcutaneous swab of the wound (SUBCUT). RESULTS: The overall SSI and IBC rates
      were 25% and 55.2%, respectively. Patients who developed SSI had an extremely
      high IBC rate (85%), and IBC patients also had a high SSI rate (68%). IBC was
      highest in the LAVAGE (26%) followed by the SUBCUT (26%), and the SUTURE (12%).
      The incidence of IBC in the LT was significantly lower than that in the ET (19%
      vs. 55%, p < 0.01), although the incidence of SSI was similar in both IBC groups.
      CONCLUSION: Shortening the exposure of the colonic mucosa decreased the incidence
      of IBC/SSI; thus, careful operations to minimize IBC are recommended.

PMID- 18636301
TI  - Distal esophageal erosion after laparoscopic adjustable gastric band placement
      with nissen fundoplication takedown.
AB  - Although primary band placement is proven to be safe, gastric band placement
      after previous operations in the area of the gastroesophageal junction remains
      controversial. Erosion into the stomach has been described after failed vertical
      banded gastroplasty conversion to laparoscopic gastric banding (LAGB), but no
      reports in the English literature are available on erosion of an adjustable
      gastric band into the esophagus after conversion operations. To our knowledge,
      this is the first case report of distal esophageal erosion after LAGB placement
      with Nissen fundoplication takedown.

PMID- 18636302
TI  - Intra-gastric band erosion from an un-inflated Lap-Band: a case report.
AB  - The increasing prevalence of morbid obesity is of public health concern
      throughout the world, and surgical intervention seems to offer the only long-term
      solution to the problem. Gastric banding is one of the available options in the
      bariatric armamentarium. As more Lap-Bands are being inserted, intragastric
      erosion is increasingly being encountered as a major complication. The case of a
      40-year-old man with intra-gastric band erosion is presented with the band never
      having been inflated, suggesting that additional factors may play a role in the
      development of erosions. The presentation, diagnostic modalities, and
      pathognomomic findings are discussed.

PMID- 18636303
TI  - A simple grafting method to repair irreparable distal biceps tendon.
AB  - Irreparable distal biceps tendon tears typically are treated using a free tendon
      graft. We asked whether our new method to fix the graft--using two suture anchors
      -yields similar results to our previous bone canal method. We compared the two
      methods for strength, endurance, and clinical findings. There were two groups,
      the suture anchor group (Group A, seven patients) and the bone canal group
      operated on before suture anchors (Group B, seven patients). The patients were
      males with a mean age at surgery of 44.9 years. The operative delay from primary
      trauma to index surgery averaged 5.9 months. The minimum followup was 2 years
      (mean, 11.1 years; range, 2-23 years). The mean arc of elbow motion was 0 degrees
      to 132 degrees, pronation 83 degrees, and supination 80 degrees. Compared with
      the contralateral side, the maximal peak torque was 84% in supination and 91% in
      pronation, and the maximal static elbow flexion strength was 94%. The Mayo elbow
      score averaged 99 in Group A and 100 in Group B. There were no major differences
      between the two groups. Our novel modification to fix a tendon graft yields equal
      clinical outcomes compared with the bone canal method for treatment of
      irreparable distal biceps tendon injuries. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18636304
TI  - Influence of silicone sheets on microvascular anastomosis.
AB  - The use of silicone products combined with free flap transfer is well established
      in reconstructive surgery. We determined the risk of thrombosis as a result of
      direct contact between the silicone sheet and the point of microanastomosis. We
      performed microvascular surgery in 24 female Chinchilla Bastard rabbits weighing
      3500 to 4000 g using two groups: Group 1 (n = 12), microanastomosis directly in
      contact with silicone sheets; and Group 2 (n = 12), microanastomosis protected by
      a 2 x 3 x 1-cm muscle cuff before being placed in contact with the silicone. We
      assessed flow-through of the microanastomosis by selective microangiography and
      histology at 1 and 3 weeks. All microanastomoses in Group 1 were occluded by
      postoperative thromboses, whereas all microanastomoses in Group 2 had adequate
      flow-through. Histologic analysis revealed thromboses in Group 1 formed from
      collagenous bundles of fiber securely attached to the intraluminal wall of the
      vessel. Three weeks after the procedure, these thromboses were canalized by
      varying small vessels. In Group 2, a slight luminal stenosis with evidence of
      infiltration of inflammatory cells at the microanastomosis line was observed
      histologically in all cases. Prefabricated flaps using silicone sheets and
      muscular cuffs placed around the anastomoses appear to reduce the risk of
      thrombosis and enhance neovascularization.

PMID- 18636305
TI  - Evidence of educational inadequacies in region-specific musculoskeletal medicine.
AB  - Recent studies suggest US medical schools are not effectively addressing
      musculoskeletal medicine in their curricula. We examined if there were specific
      areas of weakness by analyzing students' knowledge of and confidence in examining
      specific anatomic regions. A cross-sectional survey study of third- and fourth
      year students at Harvard Medical School was conducted during the 2005 to 2006
      academic year. One hundred sixty-two third-year students (88% response) and 87
      fourth-year students (57% response) completed the Freedman and Bernstein
      cognitive mastery examination in musculoskeletal medicine and a survey eliciting
      their clinical confidence in examining the shoulder, elbow, hand, back, hip,
      knee, and foot on a one to five Likert scale. We specifically analyzed
      examination questions dealing with the upper extremity, lower extremity, back,
      and others, which included more systemic conditions such as arthritis, metabolic
      bone diseases, and cancer. Students failed to meet the established passing
      benchmark of 70% in all subgroups except for the others category. Confidence
      scores in performing a physical examination and in generating a differential
      diagnosis indicated students felt below adequate confidence (3.0 of 5) in five of
      the seven anatomic regions. Our study provides evidence that region-specific
      musculoskeletal medicine is a potential learning gap that may need to be
      addressed in the undergraduate musculoskeletal curriculum.

PMID- 18636306
TI  - Disability and psychologic distress in patients with nonspecific and specific arm
      pain.
AB  - Psychological illness influences the experience and expression of pain and
      disability. We tested three null hypotheses: (1) patients with nonspecific pain
      (medically unexplained and idiopathic) and patients with specific pain (discrete
      and verifiable) are equally likely to screen for psychiatric illnesses based on a
      validated screening questionnaire; (2) the presence of psychiatric illness (from
      a screening questionnaire) will not predict whether patients have specific or
      nonspecific pain type; and (3) across all patients and regardless of whether they
      have specific or nonspecific pain, psychiatric illness will not predict
      disability as measured by the Disabilities of the Arm Shoulder and Hand (DASH)
      questionnaire. We rejected all null hypotheses. The 41 patients with nonspecific
      arm pain were more likely than the 40 patients with specific arm pain to screen
      for a somatoform disorder (34% versus 7.5%), posttraumatic stress disorder (24%
      versus 7.5%), and panic disorder (12.2% versus 5%). The presence of anxiety and
      somatoform disorders predicted pain type (nonspecific versus specific) and arm
      specific disability (DASH). Somatoform disorder was the strongest predictor of
      pain type and DASH scores. Based on a screening questionnaire, a comorbid
      psychiatric illness, a somatoform disorder in particular, is associated with
      nonspecific arm pain and arm-specific disability. LEVEL OF EVIDENCE: Level II,
      diagnostic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18636307
TI  - Evaluation of nitric oxide synthase activity, nitric oxide, and homocysteine
      levels in patients with active Behcet's disease.
AB  - Behcet's disease (BD) is a chronic, progressive disorder that affects many
      systems of the body including the eye. The aim of this study was to examine the
      effects of nitric oxide synthase activity (NOS), nitric oxide (NO*), and
      homocysteine (Hcy) levels in patients with active BD. Included in this study were
      18 male BD patients and 16 male healthy volunteers as controls. Erythrocyte NOS
      activity, (NO*) erythrocyte sedimentation rate, serum C-reactive protein, and
      plasma Hcy values in the patients with BD were significantly higher than those of
      the control group. Our results show that these parameters play a major role in
      the inflammatory reactions observed in BD.

PMID- 18636308
TI  - Limited results of group self-management education for rheumatoid arthritis
      patients and their partners: explanations from the patient perspective.
AB  - This study aimed to identify the reasons for limited results of group self
      management for RA patients and their partners from the patient perspective. Semi
      structured interviews with ten male and ten female patients who had participated
      in group self-management with or without their partner were content analyzed with
      respect to motivation to participate and the effects of the program on them. The
      limited effects of the self-management program appear to be linked with low
      motivation to participate and to change health behavior. The data show that a
      decline in health and also stressful life events might be associated with the
      disappointing effects of the program. Three strategies were proposed for
      improving the program's effects: (a) provide information about the program in
      advance to ensure that patients have appropriate expectations. (b) Enhance
      intrinsic motivation to change health behavior by counseling techniques. (c)
      Tailoring with respect to motivation and current concerns could help to form more
      homogeneous groups or could be the basis for a tailored online intervention.

PMID- 18636309
TI  - What is new in the management of Helicobacter pylori?
AB  - Since the discovery of Helicobacter pylori in the early 1980s several treatment
      regimens have been developed to effectively treat this infection. International
      guidelines have allowed consensus on the best management and improved eradication
      rates. In recent years increasing antimicrobial resistance and falling
      eradication rates highlight the need for updated guidelines. In this article we
      review the most recent European management guidelines and in view of the
      unavailability of some drugs consider new treatment regimens for the management
      of H. pylori in Ireland.

PMID- 18636310
TI  - Unique ethylene-regulated touch responses of Arabidopsis thaliana roots to
      physical hardness.
AB  - Although touch responses of plant roots are an important adaptive behavior, the
      molecular mechanism remains unclear. We have developed a bioassay for measuring
      root-bending responses to physical hardness in Arabidopsis thaliana seedlings.
      Our test requires a two-layer solid medium. Primary roots growing downward
      through an upper layer of 0.3% phytagel either penetrate the lower layer or bend
      along an interface between the upper and lower layers with different
      concentrations (0.2-0.5%, corresponding to 1.57-6.79 gw mm(-2) in hardness). In
      proportion to increasing hardness of the lower layer, we found that the
      percentage of bending roots increased and ethylene production decreased,
      suggesting an inverse relationship between the root-bending response and ethylene
      production. Studies with ethylene biosynthesis modulators and mutants also
      suggested that bending and non-bending responses of roots to medium hardness
      depend, respectively, on decreased and increased ethylene biosynthesis. In
      addition, the degrees of root-tip softening and differential root-cell growth,
      both possible factors determining root-bending response, were enhanced and
      attenuated by decreased and increased amounts of ethylene, respectively--also in
      bending roots and non-bending roots. Our findings indicate that ethylene
      regulates root touch responses, probably through a combination of root-tip
      softening (or hardening) and differential root-cell growth.

PMID- 18636311
TI  - Inhibitory effect of oxycoumarins isolated from the Thai medicinal plant Clausena
      guillauminii on the inflammation mediators, iNOS, TNF-alpha, and COX-2 expression
      in mouse macrophage RAW 264.7.
AB  - In the present study, we investigated the inhibitory effect of the known
      oxycoumarins poncitrin (3), osthol (4), and xanthoxyletin (5), newly isolated
      from Clausena guillauminii (Rutaceae), together with the known carbazoles
      heptaphylline (1) and 7-methoxyheptaphylline (2) on inducible-nitric oxide
      synthase (iNOS) expression induced by lipopolysaccharide (LPS) and the NO
      generation in RAW 264.7 mouse macrophages. Isolation of active oxycoumarins was
      guided by Western blot analysis of iNOS protein expression. These oxycoumarins
      showed an inhibitory effect on iNOS protein expression at 10 microM. Further
      examination of the inhibitory effects of these compounds on inflammation
      mediators revealed that the synthesis of nitric oxide (NO) and the protein
      expression of tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2 (COX
      2) were inhibited by 5. It was expected that these compounds show anti
      inflammatory activities.

PMID- 18636312
TI  - Rapid identification of triterpenoid saponins in the roots of Codonopsis
      lanceolata by liquid chromatography-mass spectrometry.
AB  - Liquid chromatography coupled with sequential mass spectrometry (LC-MS(n)) has
      been used to identify 3,28-bidesmosidic triterpenoid saponins, lancemaside A (1),
      foetidissimoside A (2), aster saponin Hb (3), lancemaside E (4), lancemaside B
      (5), lancemaside F (6), lancemaside G (7), lancemaside C (8), and lancemaside D
      (9) in the roots of Codonopsis lanceolata. Structural information about both the
      aglycone and the sugar moiety at the C-3 position of saponins was obtained in the
      negative-ion mode. On the other hand, positive-ion spectra mainly provide
      structural information about the sugar chains of saponins, especially the
      oligosaccharide moiety at the C-28 position. During subsequent fragmentation of
      the product ions derived from the oligosaccharide moiety at the C-28 position,
      fragments produced by sequential loss of a monosaccharide unit were observed.
      Furthermore, the structural features of two unknown saponins in the roots of C.
      lanceolata were assigned on the basis of the fragmentation patterns of the known
      saponins. These studies demonstrate that LC-MS(n) analysis has great potential
      for the identification and characterization of triterpenoid saponins in plant
      extracts.

PMID- 18636313
TI  - Thrombotic microangiopathy after treatment with bortezomib and dexamethasone in a
      patient with multiple myeloma.

PMID- 18636314
TI  - Angiotensin metabolites can stimulate receptors of the Mas-related genes family.
AB  - The Mas protooncogene encodes a G protein-coupled receptor, we identified, also
      by using the specific angiotensin-(1-7) antagonist A-779, to be associated with
      intracellular signaling of the angiotensin (Ang) II metabolite Ang-(1-7).
      Recently, Mas-related genes (Mrg) have been identified coding for the Mrg
      receptor family. All family members share high sequence homology to Mas. Most of
      them are orphan receptors. To proof whether structure similarities of the Mrg
      receptors with Mas turn them into potential receptors for Ang-(1-7) or other Ang
      metabolites, we transfected COS or HEK293 cells with an assortment of Mrg
      receptors and investigated arachidonic acid (AA) release and transcriptional
      activation by recording serum response factor (SRF) activation after stimulation
      with Ang II, Ang III, Ang IV, and Ang-(1-7). None of the investigated receptors
      activated transcription via SRF. Ang-(1-7) stimulated AA release already in
      control vector-transfected COS cells, indicating the existence of an endogenous
      receptor (A-779 sensitive). Though less pronounced than for Mas, two of the six
      studied receptors (MrgD, MRG) initiated significant AA release after stimulation
      with Ang-(1-7). Interestingly, Mas, MrgD, and MRG mediated Ang IV-stimulated AA
      release that was highest for Mas. While Ang III activated Mas and MrgX2, Ang II
      stimulated AA release via Mas and MRG. Thus, we identified other receptors of the
      Mrg family to respond on Ang-(1-7) stimulation. Furthermore, we describe first an
      AT(1)-independent direct Ang IV signaling and show that Ang II and Ang III
      mediate signaling independent of their specific receptors AT(1) and AT(2),
      whereby the receptor specificity differs.

PMID- 18636315
TI  - The role of ecto-5'-nucleotidase/CD73 in glioma cell line proliferation.
AB  - Malignant gliomas are the most common and devastating primary tumors in the brain
      and, despite treatment, patients with these tumors have a poor prognosis. The
      participation of ecto-5'-NT/CD73 per se as a proliferative factor, being involved
      in the control of cell growth, differentiation, invasion, migration and
      metastasis processes has been previously proposed. In the present study, we
      evaluated the activity and functions of ecto-5'-NT/CD73 during the proliferation
      process of rat C6 and human U138MG glioma cell lines. Increasing confluences and
      culture times led to an increase in ecto-5'-NT/CD73 activity in both C6 and
      U138MG glioma cells. RT-PCR analysis and flow cytometry analysis showed a
      significant increase in ecto-5'-NT/CD73 mRNA and protein levels, respectively,
      comparing confluent with sub-confluent cultures in human U138MG glioma cells.
      Ecto-5'-nucleotidase/CD73 may regulate the extracellular adenosine 5'
      monophosphate (AMP) and adenosine levels. Treatment with 1 microM APCP, a
      competitive ecto-5'-NT/CD73 inhibitor, caused a significant reduction of 30% in
      glioma cell proliferation. In addition, 100 microM adenosine increases cell
      proliferation by 36%, and the treatment with adenosine plus NBTI and
      dipyridamole, produced an additional and significant increase of on cell
      proliferation. The inhibitory effect on cell proliferation caused by APCP was
      reverted by co-treatment with NBTI and dipyridamole. AMP (1 mM and 3 mM)
      decreased U138MG glioma cell proliferation by 29% and 42%, respectively. Taken
      together, these results suggest the participation of ecto-5'-NT/CD73 in cell
      proliferation and that this process is dependent upon the enzyme's production of
      adenosine, a proliferative factor, and removal of AMP, a toxic molecule for
      gliomas.

PMID- 18636316
TI  - Hypoxic remodelling of Ca(2+) signalling in proliferating human arterial smooth
      muscle.
AB  - Ca(2+) homeostasis in proliferating smooth muscle (SM) cells strongly influences
      neointima formation, which can cause failure of coronary artery bypass surgery.
      During surgical procedures and subsequent revascularization, SM cells are also
      exposed to a period of hypoxia. Problems with bypass surgery in general involve
      neointima formation which is in turn dependent on SM proliferation and migration.
      Here, we have directly monitored [Ca(2+)](i) fluorimetrically in proliferating
      internal mammary artery (IMA) SM cells, and investigated how this is modulated by
      chronic hypoxia (CH; 24 h, 2.5% O(2)). IMA is the most successful replacement
      conduit vessel in bypass grafts. Basal [Ca(2+)](i) was unaffected by CH, but
      removal of extracellular Ca(2+) evoked far smaller reductions in [Ca(2+)](i) than
      were seen in normoxic cells. Voltage-gated Ca(2+) entry was suppressed in CH
      cells, and this was attributable to activation of the transcriptional regulator,
      hypoxia inducible factor. Furthermore, the relative contributions to voltage
      gated Ca(2+) entry of L- and T-type Ca(2+) channels was markedly altered, with T
      type channels becoming functionally more important in CH cells. Agonist-evoked
      mobilization of Ca(2+) from intracellular stores was not affected by CH, whilst
      subsequent capacitative Ca(2+) entry was modestly suppressed. Our data provide
      novel observations of the remodelling of Ca(2+) homeostasis by CH in IMASM cells
      which may contribute to their superior patency as coronary bypass grafts.

PMID- 18636318
TI  - Sustained release of antibiotic from polyurethane coated implant materials.
AB  - Implant associated infections are of increasing importance. To minimize the risks
      of implant-associated infections recent biomedical strategies have led to the
      modification of the medical device surfaces. The modifications are in the terms
      of increasing surface biocompatibility and decreasing bacterial adherence, which
      can be achieved by applying a coating of biocompatible polymer onto the said
      surfaces. Entrapping anti-infective agents in a polymer matrix provides an
      approach to kill bacteria and combat the possibility of any residual infection.
      We have prepared a biodegradable polyester urethane coat for implant materials,
      which have the property to accommodate antibiotics within itself. These
      polyurethane coating materials were characterized by FTIR spectroscopy, swelling
      property in SBF, gravimetric analysis, drug release, and biocompatibility study.
      Drug release rates, bacterial colonization and morphological features were also
      evaluated to predict and understand the antimicrobial activity of these delivery
      systems. Drug release characteristics were investigated and the physico-chemical
      mechanisms of the delivery were discussed. Results suggest that the polyester
      urethane can be used as an implant coating material and can be used as a matrix
      for the sustained delivery of anti-infective agent.

PMID- 18636317
TI  - Nutrigenomic basis of beneficial effects of chromium(III) on obesity and
      diabetes.
AB  - Insulin resistance has been shown to be the major contributing factor to the
      metabolic syndrome, which comprises a cluster of risk factors for metabolic
      aberrations such as obesity, dyslipidemia, hypertension, and hyperglycemia.
      Additionally, insulin resistance has been associated with the occurrence of
      cardiovascular disease and type 2 diabetes. Epidemiological studies indicate that
      obesity and diabetes have become alarmingly prevalent in recent years.
      Substantial evidence suggests that dietary interventions and regular exercise
      greatly improve body mass index and lipid profile as well as alleviate insulin
      resistance. Therefore, dietary supplements such as insulin-sensitizing agents may
      be beneficial in the prevention and treatment of obesity and type 2 diabetes.
      Numerous in vitro and in vivo studies suggest that chromium supplements,
      particularly niacin-bound chromium or chromium-nicotinate, may be effective in
      attenuating insulin resistance and lowering plasma cholesterol levels. Utilizing
      the powerful technology of nutrigenomics to identify the genes regulated by
      chromium supplementation may shed some light on the underlying mechanisms of
      chromium-gene interactions, and thus provide strategies to mitigate and prevent
      insulin-resistance-related disorders.

PMID- 18636319
TI  - Investigation of the drug-drug interaction between alpha-lipoic acid and
      valproate via mitochondrial beta-oxidation.
AB  - PURPOSE: To investigate the potential drug-drug interaction (DDI) between lipoic
      acid (LA) and valproate (VA) via the mitochondrial beta-oxidation pathway in
      rats. METHODS: In vitro mitochondrial assays were performed to compare the
      biotransformation of VA to valproyl-CoA (VA-CoA), in the absence and presence of
      LA. In vitro microsomal and protein binding assays were performed to elucidate
      their potential DDI at the microsomal metabolism and distribution levels. A
      pharmacokinetic study was conducted in Lister Hooded rats to ascertain the in
      vivo DDI between LA and VA. RESULTS: LA was shown to decrease significantly (p <
      0.05) the in vitro formation of VA-CoA in a concentration-dependent manner. Our
      in vitro assay results confirmed that there was minimal interaction between LA
      and VA in microsomal metabolism and protein binding. Based on the pharmacokinetic
      data, the absolute bioavailability of VA was determined to be 1.3 in the presence
      of LA. CONCLUSIONS: Our study demonstrated for the first time that there is a
      potential DDI between LA and VA at the mitochondrial beta-oxidation level. While
      further clinical study is essential, our preliminary finding suggested that
      medical practitioners need to be prudent when managing epileptic patients who are
      co-administered with both VA and LA.

PMID- 18636320
TI  - Including information on the therapeutic window in bioequivalence acceptance.
AB  - PURPOSE: A novel bioequivalence limit is proposed taking into account the
      therapeutic window. METHODS: The therapeutic range is introduced as the ratios
      maximum tolerated dose/therapeutic dose (MTD/D) and the therapeutic dose/lowest
      effective dose. The performance of the new acceptance range was compared with the
      methods of Schuirmann and Karalis. The method was retrospectively applied to data
      of three drugs with a narrow therapeutic window (phenytoin, theophylline and
      digoxin). RESULTS: Simulations and examples show that the resulting
      bioequivalence limits are (1) narrow for narrow-index drugs, (2) expanded for
      highly variable drugs with a wide therapeutic window and (3) similar to the
      classical limits for less variable drugs with a wide therapeutic range.
      CONCLUSIONS: The approach has the desirable property of resulting in a more
      narrow acceptance range for doses near the boundaries of the therapeutic window
      and a wider acceptance range for products with a broad therapeutic window.

PMID- 18636322
TI  - Including injured workers without compensated time loss in Cox regression models:
      analyzing time loss using all available data.
AB  - INTRODUCTION: Cox proportional hazards regression is commonly used to analyze
      time loss duration, but statistical packages conventionally exclude cases with no
      recorded follow-up time. For this and other substantive reasons, many researchers
      limit time loss analyses to the subset of workers who received time loss
      compensation. This can exclude both injured workers who missed no work days and
      those missing up to a week of work. For some research questions, excluding cases
      where injury is reported but no time loss is recorded may result in significant
      ascertainment bias. We present a novel technique based on standard survival
      analysis methods to allow for the inclusion of all cases when appropriate.
      METHODS: A simple technique to allow standard statistical software to include
      both medical-only and time loss claims in Cox regression is illustrated by
      example and compared with a two-part model using a time-varying step function to
      allow regression effects to change over time. RESULTS: We showed that a pooled
      analysis is obtained by simply adding a small constant to the time loss duration
      variable. This technique produced appropriate estimates while accounting for
      censoring when a suitable method was used for tied event times. Using a formal
      statistical framework, the combined model was justified as a special case of the
      more standard two-part model approach. CONCLUSIONS: When it is desirable to have
      a single pooled outcome estimate for injured workers with both medical-only and
      time loss claims, all claims can be combined into one statistical model. This may
      have particular utility for research questions where the risk factor or
      intervention of interest would be expected to affect time loss duration beginning
      upstream of claim filing or statutory compensation waiting periods. This novel
      alternative modeling strategy expands the tool kit available for analyzing time
      loss data.

PMID- 18636321
TI  - Multifunctional polymeric micelles for enhanced intracellular delivery of
      doxorubicin to metastatic cancer cells.
AB  - PURPOSES: To develop multifunctional RGD-decorated poly(ethylene oxide)-b
      poly(ester) based micelles and assess their pH-triggered core degradation and
      targeted drug release in tumor cells that overexpress RGD receptors. METHODS:
      Novel poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) based
      copolymers modified with RGD ligands on PEO and pendent functional groups on PCL,
      i.e., GRGDS-PEO-b-poly(alpha-benzylcarboxylate-epsilon-caprolactone) (GRGDS-PEO-b
      PBCL) and GRGDS-PEO-b-poly(alpha-carboxyl-epsilon-caprolactone) (GRGDS-PEO-b
      PCCL), were synthesized. Chemical conjugation of doxorubicin (DOX) to PCCL core
      produced GRGDS-PEO-b-P(CL-DOX) micellar conjugates, while GRGDS-PEO-b-PBCL were
      used to physically encapsulate DOX. For both systems, micellar core degradation,
      drug release, intracellular drug uptake/disposition, and cytotoxicity against
      B16F10 metastatic cells were investigated. RESULTS: The PBCL and P(CL-DOX) cores
      were found resistant to degradation in pH 7.2, but showed 10% and 40% loss in
      core molecular weight in pH 5.0 within 144 h, respectively. Preferential release
      of DOX and DOX derivatives from PBCL and P(CL-DOX) cores was noted in pH 5.0,
      respectively. The GRGDS-modified micelles showed enhanced cellular
      internalization through endocytosis, increased intracellular DOX release, nuclear
      localization, and improved cytotoxicity against metastatic B16F10 cells compared
      to their unmodified counterparts. CONCLUSIONS: The results clearly suggest a
      promise for the development of multifunctional polymeric micelles with RGD ligand
      decorated shell and endosomal pH-triggered degradable core for selective DOX
      delivery to metastatic cancer cells.

PMID- 18636323
TI  - Acculturation and depressive symptoms among pregnant and postpartum Latinas.
AB  - OBJECTIVES: Among childbearing Latinas, higher acculturation has been found to be
      significantly associated with increased risk for mental health problems, although
      these findings have been inconsistent. The aims of this study are to assess and
      compare the prevalence of elevated depressive symptoms among pregnant and
      postpartum U.S.- and Mexican-born Latinas, and to describe the relation of
      elevated depressive symptoms and acculturation indicators. METHODS: A convenience
      sample of 439 pregnant and postpartum Latinas attending Public Health Clinics in
      San Antonio, Texas was screened for depressive symptoms using the Center for
      Epidemiologic Studies Depression (CES-D) Scale. Women with a score of 21 or
      greater were classified as having elevated depressive symptoms. Sociodemographic
      data, including birth country and language of interview, were collected as
      indicators of acculturation. RESULTS: 21% of the sample had moderate depressive
      symptoms; 15% met the threshold for high depressive symptoms. Bivariate analysis
      showed Latinas who were U.S.-born, single, preferred English or were pregnant
      were more likely to express elevated levels of depressive symptoms. Being U.S.
      born, pregnant and single was significantly associated with moderate levels of
      depressive symptoms in logistic regression analyses controlling for other
      variables in the model. Controlling for other variables, being pregnant and
      single was significantly associated with high levels of depressive symptoms.
      CONCLUSIONS: Higher acculturation, pregnancy and single status were positively
      associated with elevated depressive symptoms. Screening for depression during
      pregnancy is important for this population group, given Latinas' high rates of
      fertility and births to single women, particularly among more acculturated, U.S.
      born Latinas.

PMID- 18636324
TI  - Psychosocial and behavioral predictors of partner notification after HIV and STI
      exposure and infection among MSM.
AB  - Partner notification (PN) is an essential element of local and state-level
      HIV/STI prevention and control programs. The current study quantitatively
      assessed the psychosocial and behavioral predictors of PN use among men who have
      sex with men (MSM) (n = 189) using multivariable logistic regression procedures.
      STI history or being HIV-infected were significant predictors of having notified
      past sexual partners of HIV/STI exposure; engaging in unprotected insertive anal
      sex and using poppers during sex in the 12 months prior to enrollment resulted in
      greater odds of PN. Symptoms of social anxiety and having a drinking problem were
      significant predictors of future willingness to use state department of public
      health PN services. Efforts to increase PN acceptability should focus on HIV
      uninfected MSM, particularly those with STI history. Results suggest how to
      increase acceptability and use of PN as a public health strategy and underscore
      the need for counseling as part of the notification process.

PMID- 18636325
TI  - Reducing HIV and partner violence risk among women with criminal justice system
      involvement: a randomized controlled trial of two motivational interviewing-based
      interventions.
AB  - Women with histories of incarceration show high levels of risk for HIV and
      intimate partner violence (IPV). This randomized controlled trial with women at
      risk for HIV who had recent criminal justice system involvement (n = 530)
      evaluated two interventions based on Motivational Interviewing to reduce either
      HIV risk or HIV and IPV risk. Baseline and 3, 6, and 9-month follow-up
      assessments measured unprotected intercourse, needle sharing, and IPV.
      Generalized estimating equations revealed that the intervention groups had
      significant decreases in unprotected intercourse and needle sharing, and
      significantly greater reductions in the odds and incidence rates of unprotected
      intercourse compared to the control group. No significant differences were found
      in changes in IPV over time between the HIV and IPV group and the control group.
      Motivational Interviewing-based HIV prevention interventions delivered by county
      health department staff appear helpful in reducing HIV risk behavior for this
      population.

PMID- 18636327
TI  - Terpenoids and breast cancer chemoprevention.
AB  - Cancer chemoprevention is defined as the use of natural or synthetic agents that
      reverse, suppress or arrest carcinogenic and/or malignant phenotype progression
      towards invasive cancer. Phytochemicals obtained from vegetables, fruits, spices,
      herbs and medicinal plants, such as terpenoids, carotenoids, flavanoids, phenolic
      compounds, and other groups of compounds have shown promise in suppressing
      experimental carcinogenesis in various organs. Recent studies have indicated that
      mechanisms underlying chemopreventive action may include combinations of anti
      oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects. Further,
      modification of drug-metabolizing enzymes, and influences on cell cycling and
      differentiation, induction of apoptosis, and suppression of proliferation and
      angiogenesis that play a role in the initiation and secondary modification of
      neoplastic development, have also been under investigation as possible
      mechanisms. This review will highlight the biological effects of terpenoids as
      chemopreventive agents on breast epithelial carcinogenesis, and the utility of
      intermediate biomarkers as indicators of premalignancy. Selected breast
      chemoprevention trials are discussed with a focus on strategies for trial design,
      and clinical outcomes. Future directions in the field of chemoprevention are
      proposed based on recently acquired mechanistic insights into breast
      carcinogenesis.

PMID- 18636328
TI  - The epidemiology of obesity and gastrointestinal and other diseases: an overview.
AB  - The worldwide prevalence of obesity continues to increase, with devastating
      implications for overall health. Epidemiological trends indicate the primary
      contributors are environmental (e.g., increased caloric intake, lack of
      exercise), although the evidence is surprisingly equivocal. Increased body mass
      index (BMI) is associated with an increase in all-cause mortality and in diseases
      related to this increasing mortality rate, such as diabetes mellitus,
      cardiovascular disease, and cancer, including those of the gastrointestinal
      system. Some of these associations are even more pronounced when obesity is
      measured by waist-to-hip ratio, a marker of visceral adipose tissue, versus BMI.
      Higher BMI is related to increased risk of developing gall stones, and obese
      patients experience GI symptoms, such as vomiting and diarrhea, more often
      compared with those of normal body mass. Although the exact cause remains
      uncertain, these symptoms may be connected to eating habits or to changes in
      gastrointestinal motility.

PMID- 18636329
TI  - Over-expression of alpha-actinin with a GFP fusion protein is sufficient to
      increase whole-cell stiffness in human osteoblasts.
AB  - Osteoblasts respond to shear stress by simultaneously increasing their whole-cell
      stiffness and up-regulating the cytoskeletal crosslinking protein alpha-actinin.
      The stiffness of reconstituted cytoskeletal networks increases following the
      addition of alpha-actinin, but the effect of alpha-actinin on whole-cell
      mechanical behavior has not been investigated. The hypothesis of this study was
      that increasing alpha-actinin in the cytoskeleton would be sufficient to increase
      whole-cell stiffness. hFOB osteoblasts were transfected with a plasmid for GFP
      tagged alpha-actinin, resulting in a 150% increase in the amount of alpha
      actinin. The GFP-alpha-actinin fusion protein co-fractionated with the
      cytoskeleton and co-localized to the same regions of the cytoskeleton as
      endogenous alpha-actinin. Whole-cell mechanical behavior was measured by atomic
      force microscopy using a 25 mum diameter microsphere as an indenter. The whole
      cell stiffness of cells over-expressing GFP-alpha-actinin was 60% higher than
      cells expressing only endogenous alpha-actinin (p < 0.002), which was within the
      range of mechanical behavior observed in osteoblastic cells exposed to 1 and 2 Pa
      of fluid shear. These results indicate that the up-regulation of alpha-actinin
      synthesis in osteoblasts is sufficient to alter the whole-cell mechanical
      behavior and highlights the potential role of alpha-actinin to reinforce cells
      against mechanical loads.

PMID- 18636330
TI  - Craniopharyngioma surgery.
AB  - Ideal surgical treatment of craniopharyngiomas remains a major challenge for
      neurosurgeons. Craniopharyngiomas grow in the deep-seated hypothalamic area that
      is paramount for vegetative, emotional and endocrine function, and for
      maintaining worthwhile life. The benign histological nature of craniopharyngiomas
      belies their biological behavior and the propensity to recur is a major threat.
      Surgical treatment has to weigh the risk of hypothalamic damage against the risk
      of tumor recurrence or progression. Both aggressive surgery and conservative
      minor surgery followed by radiotherapy has been proclaimed by the proponents of
      different schools. During the past decade, the pendulum has swung back to surgery
      with the attempt at radical removal. Refined neurosurgical techniques and
      innovative approaches yielded improved surgical results. The contemporary
      neurosurgical strategy of treating craniopharyngiomas with early and late outcome
      data is presented. Neurosurgical therapy is only beneficial in the context of an
      interdisciplinary treatment concept as discussed here.

PMID- 18636331
TI  - Mechanisms of action of ligands of potential-dependent sodium channels.
AB  - Potential-dependent sodium channels play a leading role in generating action
      potentials in excitable cells. Sodium channels are the site of action of a
      variety of modulator ligands. Despite numerous studies, the mechanisms of action
      of many modulators remain incompletely understood. The main reason that many
      important questions cannot be resolved is that there is a lack of precise data on
      the structures of the channels themselves. Structurally, potential-dependent
      sodium channels are members of the P-loop channel superfamily, which also include
      potassium and calcium channels and glutamate receptor channels. Crystallization
      of a series of potassium channels showed that it was possible to analyze the
      structures of different members of the superfamily using the "homologous
      modeling" method. The present study addresses model investigations of the actions
      of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well
      as local anesthetics. Comparison of experimental data on sodium channel ligands
      with x-ray analysis data allowed us to reach a new level of understanding of the
      mechanisms of channel modulation and to propose a series of experimentally
      verifiable hypotheses.

PMID- 18636333
TI  - Predicting improvement of transitioning young people in the partnerships for
      youth transition initiative: findings from a multisite demonstration.
AB  - Prior research has indicated that young people with serious mental health
      conditions show poorer progress and greater challenges in the transition to
      adulthood, as reflected by lower rates of employment and postsecondary education,
      higher rates of criminal justice involvement, and greater interference in daily
      activities from mental health and substance use disorders. Little knowledge
      exists, however, regarding improvement on these indicators among young people
      enrolled in community-based transition support programs and individual
      characteristics that might moderate this improvement. This study describes rates
      of improvement on indicators of transition progress and challenges among young
      people enrolled in a multisite demonstration of transition support programs.
      Young people in the study showed increased rates of progress and decreased rates
      of challenges over four quarters of enrollment. Moderation of these changes by
      individual characteristics including demographic, historical, and diagnostic
      variables suggested ways of improving transition support programs and avenues for
      future research.

PMID- 18636332
TI  - Trauma and psychosocial predictors of substance abuse in women impacted by
      HIV/AIDS.
AB  - The purpose of this study was to estimate the relative contributions of trauma,
      chronic stress burden, depression, anxiety, social support, and social
      undermining in predicting alcohol and drug abuse, and whether ethnicity moderated
      these relationships. A multi-ethnic sample of 288 HIV-positive and HIV-negative
      women was recruited. Multiple group path analysis indicated that greater drug
      dependence was associated with being HIV+, more depression, and higher chronic
      burden. Trauma was related only to anxiety. Also, greater alcohol dependence was
      associated with more depression and more social undermining, and these effects
      were moderated by ethnicity. African American and Latina women evidenced
      different relationships between depression, social support and social
      undermining. Depression, social support and social undermining served as
      intervening variables in influencing the relationships between the other
      psychosocial variables and drug and alcohol dependence. The implications of these
      findings for alcohol and drug abuse research and services are discussed.

PMID- 18636334
TI  - Effect of charged and non-ionic membrane additives on physicochemical properties
      and stability of niosomes.
AB  - The aim of this study was to investigate an influence of different types of
      membrane additives including negative charge (dicetylphosphate, DCP), positive
      charge (stearylamine, STR) and non-ionic molecule (cholesteryl poly-24
      oxyethylene ether, SC24) on the physicochemical properties of drug-free and drug
      loaded niosomes. Salicylic acid having different proportions of ionized and
      unionized species at different pH was selected as a model drug. The niosomes were
      composed of 1:1 mole ratio of Span 60: cholesterol as vesicle forming agents. The
      results show that incorporation of salicylic acid to the niosomes did not affect
      zeta potential values; however, addition of the membrane additives changed the
      zeta potential depending on the type of the additives. Transmission electron
      microscopy revealed that niosomes had unilamellar structure. The particle sizes
      of all developed niosomes were between 217 to 360 nm. The entrapment efficiency
      (%E.E.) of all salicylic acid niosomes at pH 3 was higher than that of niosomes
      at pH 5, indicating that salicylic acid in unionized form was preferably
      incorporated in niosomes. Furthermore, the positively charged niosomes showed the
      highest %E.E. of salicylic acid owing to electrostatic attraction between STR and
      salicylic acid. After 3 months of storage at 4 degrees C, the particle size of
      the niosomes remained in the nanosize range except for DCP salicylic acid
      niosomes at pH 3 whose size increased due to an instability of DCP at low pH. In
      addition, all niosomes showed no leakage of the salicylic acid after 3 months of
      storage indicating the good stability.

PMID- 18636335
TI  - Small-angle X-ray diffraction studies of a molluscan smooth muscle in the catch
      state.
AB  - Small-angle X-ray diffraction patterns from the anterior byssus retractor muscle
      of Mytilus edulis in the resting, active, and catch states were examined closely
      to elucidate the structural features of catch. The specimens were isometrically
      contracted by stimulation with acetylcholine. The specimens that produced strong
      tensions in both the active and catch states showed noticeable structural change
      in the thick filaments. Although the tension was weaker in the catch state than
      in the active state, the axial spacings of the 14.5 nm meridional reflection and
      its higher order reflections from the thick filaments were more elongated in the
      catch state than in the active state. This means that the thick filaments were
      stretched more strongly in the catch state than in the active state.

PMID- 18636337
TI  - A comparison of techniques to sample salamander assemblages along highland
      streams of Maryland.
AB  - Amphibians may be useful indicators of biological condition in small streams so
      determining which sampling technique maximizes encounters at the least cost and
      at the optimal time of year is important. Area constrained surveys (ACS), used by
      the Maryland Biological Stream Survey, were tested against cover board surveys,
      drift fences with pitfall and funnel traps, quadrat leaf litter searches, and
      leaf litter bags. Sixteen, 100 m-long sites were established in headwater streams
      in the Savage River State Forest in Garrett County, Maryland. Each technique was
      randomly assigned to a 25 m stream section within each overall sampling site, and
      sites were sampled once each month from May to October (2005) with additional
      sampling in March and April (2006). Area constrained surveys yielded means of 2.7
      taxa and 14.9 total individuals per sampling visit, which was significantly
      higher than the yield of all other methods in all months except October and
      March, when yields were low for all techniques. Area constrained surveys were
      also significantly more cost-effective per taxon and per individual compared to
      all other methods. September produced the most taxa and individuals, October and
      March produced the least, and yields for April through August were similar to
      September. We employed removal sampling at four sites in April 2006, but
      abundance could not be estimated because a significant linear decrease in the
      accumulated catch versus catch per unit effort did not occur for three of the
      sites.

PMID- 18636336
TI  - Effect of the behavior and availability of heavy metals on the characteristics of
      the coastal soils developed from alluvial deposits.
AB  - An investigation of the behavior and availability of heavy metals (HMs), i.e.,
      Cu, Zn, Ni, Pb, Cr, and Cd, based on the analysis of correlation between HMs and
      physical and chemical properties of coastal soils developed from alluvial
      deposits in Shanghai, China, has been conducted, in order to reveal the effect of
      the soil formation and development and the unsuited human activities on the
      activities and mobility of HMs in agricultural soils. The results showed that (1)
      the soils still meet the needs of plant growth due to the moderate fertility with
      a soil texture of silty loam although the content of organic matters is lower,
      (2) total heavy metal content had a increase trend from the inland area to the
      coastal area, indicating the impact of alluvial deposits related to the soil
      formation on the distribution of HMs; (3) a significant positive correlation was
      found between HMs and some soil properties (i.e., clay content, cation exchange
      capacity, organic matters, total Phosphorous content, etc.), indicating that the
      regulation of these properties could give some great effect on the behavior and
      availability of HMs; (4) the positive correlation among Cu, Zn, Ni, and Cd, and
      between Pb and Cr is very significant, suggesting the most similar, if not the
      same, origins of HMs; These findings are helpful to the soil remediation,
      fertility adjustment, and plant cultivation.

PMID- 18636338
TI  - Changes in structural attributes of plant communities along disturbance gradients
      in a dry deciduous forest of Western Ghats, India.
AB  - Changes in tree and understory plant diversity and community composition in two
      sites at different disturbance levels were studied on the Anaikatty hills,
      Western Ghats. Systematic sampling using small scale permanent quadrates (50 x 20
      m for trees, 5 x 5 m for shrubs/saplings, 1 x 1 m for herbs/seedlings) enumerated
      3,376 individuals of trees (106 species), 8,599 of individuals shrubs (122
      species) and 16,659 individuals of herbs (145 species). Among the two sites,
      species richness and diversity were highest for low disturbed stand (98 and 3.9,
      respectively) compared to high disturbed site (45 and 2.71, respectively). Result
      of cluster analysis showed that two distinct clusters were formed on the basis of
      disturbance of the area in concordance with our field observation. A total of 37
      species were common to both sites, sixty one species exclusively found in low
      disturbed site and eight species were pertained to highly disturbed site. Mann
      Whitney test based on Monte Carlo approximation at 95% confidence levels
      indicated that both populations were not entirely different. The clear difference
      was only observed for average basal area of trees, density of seedlings, number
      of species, density and diversity for shrubs and number of species and diversity
      for herb. The species composition were different in two stand i.e., Nothopegia
      racemosa-Albizia amara-Maba neilghrrensis in low disturbed stand and Albizia
      amara-Pleiospermium alatum-Bauhinia racemosa in high disturbed stand. The major
      disturbance factors identification using spearman rank correlation indicated that
      the disturbance in low disturbed habitats were mostly from past logging followed
      by cutting and illicit felling and grazing, while in high disturbed habitats, it
      was human presence, past logging and lopping and fuel wood collection.

PMID- 18636339
TI  - Novel multicomponent reactions involving isoquinoline or phenanthridine and
      activated acetylenic ester in the presence of heterocyclic NH or 1,3-dicarbonyl
      compounds.
AB  - Multicomponent reactions involving azines (phenanthridine or isoquinoline) and
      dimethyl acetylenedicarboxylate were undertaken in the presence of heterocyclic
      NH compounds (indole, 2-methyl indole, 3-methyl indole, carbazole and 3,6
      dibromocarbazole) or 1,3-dicarbonyl compounds such as N,N'-dimethylbarbituric
      acid, 1,3-diethyl-2-thiobarbituric acid, acetylacetone, 1,3-diphenyl-1,3
      propandione and cyclopentan-1,3-dione to generate enaminoesters in good yields.

PMID- 18636340
TI  - Compositional inheritance: comparison of self-assembly and catalysis.
AB  - Genetic inheritance in modern cells is due to template-directed replication of
      nucleic acids. However, the difficulty of prebiotic synthesis of long information
      carrying polymers like RNA raises the question of whether some other form of
      heredity is possible without polymers. As an alternative, the lipid world theory
      has been proposed, which considers non-covalent assemblies of lipids, such as
      micelles and vesicles. Assemblies store information in the form of a non-random
      molecular composition, and this information is passed on when the assemblies
      divide, i.e. the assemblies show compositional inheritance. Here, we vary several
      important assumptions of previous lipid world models and show that compositional
      inheritance is relevant more generally than the context in which it was
      originally proposed. Our models assume that interaction occurs between nearest
      neighbour molecules only, and account for spatial segregation of molecules of
      different types within the assembly. We also draw a distinction between a self
      assembly model, in which the composition is determined by mutually favourable
      interaction energies between the molecules, and a catalytic model, in which the
      composition is determined by mutually favourable catalysis. We show that
      compositional inheritance occurs in both models, although the self-assembly case
      seems more relevant if the molecules are simple lipids. In the case where the
      assemblies are composed of just two types of molecules, there is a strong analogy
      with the classic two-allele Moran model from population genetics. This highlights
      the parallel between compositional inheritance and genetic inheritance.

PMID- 18636341
TI  - Is E/E' reliable in patients with regional wall motion abnormalities to estimate
      left ventricular filling pressure?
AB  - BACKGROUND: There is limited data on the diagnostic utility of the transmitral to
      mitral annular velocity (E/E') by tissue Doppler imaging (TDI) in the presence of
      regional wall motion abnormalities (RWMA). We aimed to investigate whether the
      E/E' is reliable in estimating left ventricular filling pressure (LVFP) despite
      RWMA. METHODS: One hundred thirty consecutive patients with myocardial infarction
      (MI) and subsequent RWMA referred for cardiac catheterization and
      echocardiography to measure LV pre-A pressure (LVP(PRE-A)) and Doppler signals
      from the mitral inflow with tissue Doppler imaging (TDI) of the mitral annulus.
      All patients were classified into three groups according to RWMA of the segment
      adjacent to the E'-measuring point using TDI: 83 patients with normal wall
      motions of the basal septal and basal lateral segments (group A); 28 patients
      with RWMA of the basal septum (group B); and 19 patients with RWMA of the basal
      lateral segment (group C). RESULTS: Septal E/E' correlated with LVP(PRE-A) in
      groups A and C (r = 0.383, P < 0.001; r = 0.482, P = 0.037, respectively).
      Lateral E/E' and LVP(PRE-A) showed good correlation in groups A, B and C (r =
      0.470, P < 0.001; r = 0.416, P = 0.028; r = 0.727, P < 0.001, respectively). The
      largest area under the receiver operating curve was obtained by the lateral E/E'
      for the prediction of a high LVFP, irrespective of the location of RWMA.
      CONCLUSIONS: In selected patients with abnormal wall motion of the basal septum,
      E/E' measured at the septum was not representative for LVFP. Lateral E/E' is
      reliable for the prediction of high LVFP, regardless of the site of RWMA.

PMID- 18636342
TI  - Occurrence of fumonisin B(1) in corn from the main corn-producing areas of China.
AB  - Fumonisin B(1) (FB(1)) is the most abundant of the fumonisin mycotoxins, mainly
      produced in maize by F. verticillioides and F. proliferatum. A total of 282 corn
      samples harvested in 2005 from six provinces, the main corn-producing areas of
      China, were analyzed for FB(1) using high-performance liquid chromatography. All
      samples except one were (99.6%) positive for FB(1) at levels varying from 3 to
      71,121 ng/g with mean and median levels for all samples of 6,662 and 1,569 ng/g,
      respectively. During an analysis of the distribution pattern for FB(1), it became
      apparent that 43.6% of tested samples had FB(1) concentrations below 1,000 ng/g,
      while 25.2% contained in excess of 5,000 ng/g. The average exposure to FB(1) (1.1
      microg/kg body weight/day) is within the provisional maximum tolerable daily
      intake of 2 microg/kg body weight/day set by the Joint FAO/WHO Expert Committee
      on Food Additives.

PMID- 18636343
TI  - Sociology and bioethics.

PMID- 18636344
TI  - Regulating trust in pediatric clinical trials.
AB  - The participation of minors in clinical trials is essential to provide safe and
      effective medical care to children. Because few drugs have been tested in
      children, pediatricians are forced to prescribe medications off-label with
      uncertain efficacy and safety. In this article, we analyze how the enrollment of
      minors in clinical trials is negotiated within relationships of mutual trust
      between clinicians, minors, and their parents. After a brief description of the
      problems associated with involving minors in clinical research, we consider how
      existing "relationships of trust" can be used as a place where the concerns of
      research subjects can be more fully discussed and addressed. Building on the
      tacit recognition of trust found in The European Clinical Trials Directive we
      make policy recommendations that allow for clearer, more ethically informed
      guidelines for enrolling minors in clinical research.

PMID- 18636345
TI  - Plasticity of the Hsp90 chaperone machine in divergent eukaryotic organisms.
AB  - Hsp90 is critical for the regulation and activation of numerous client proteins
      critical for diverse functions such as cell growth, differentiation, and
      reproduction. Cytosolic Hsp90 function is dependent on a battery of co-chaperone
      proteins that regulate the ATPase activity of Hsp90 function or direct Hsp90 to
      interact with specific client proteins. Little is known about how Hsp90 complexes
      vary between different organisms and how this affects the scope of clients that
      are activated by Hsp90. This study determined whether ten distinct Hsp90 co
      chaperones were encoded by genes in 19 disparate eukaryotic organisms.
      Surprisingly, none of the co-chaperones were present in all organisms. The co
      chaperone Hop/Sti1 was most widely dispersed (18 out of 19 species), while
      orthologs of Cdc37, which is critical for the stability and activation of diverse
      protein kinases in yeast and mammals, were identified in only nine out of 19
      species examined. The organism with the smallest proteome, Encephalitozoon
      cuniculi, contained only three of these co-chaperones, suggesting a correlation
      between client diversity and the complexity of the Hsp90 co-chaperone machine.
      Our results suggest co-chaperones are critical for cytosolic Hsp90 function in
      vivo, but that the composition of Hsp90 complexes varies depending on the
      specialized protein folding requirements of divergent species.

PMID- 18636346
TI  - A novel method for analyzing mitochondrial movement: inhibition by paclitaxel in
      a pheochromocytoma cell model.
AB  - A method was developed to assess mitochondrial movement in the living cell that
      is dependent, in part, on microtubule and/or associating protein interactions.
      The leader sequence from cytochrome-c was used to drive DsRed2 fluorescent
      proteins to accumulate in the mitochondria, thus enabling to follow mitochondrial
      (cytochrome-c's) movement. For calculating the percentage of mitochondrial
      movement, an image-processing program was used (ImageJ). Paclitaxel, an antitumor
      agent, is a potent microtubule-stabilizing agent that increases the stability of
      tubulin polymers, inhibiting mitosis and mitochondrial activity in dividing
      cells. Here, we tested whether paclitaxel inhibits mitochondrial movement in
      pheochromocytoma cells (a neuronal model, when tested in a differentiated state).
      While a 2-day exposure to paclitaxel resulted in cellular toxicity (measured as
      inhibition of mitochondrial activity), 2-3 h exposure to paclitaxel were
      sufficient to inhibit mitochondrial movement as assessed in 10-20-s imaging
      sessions in living cells. Mitotracker deep-red staining validated the staining
      obtained with DsRed2-cytochrome-c and identified intact mitochondria. Results
      showed a significant paclitaxel dose-dependent inhibition of mitochondrial
      movement. This new method should enable further assessment of microtubule
      interacting drugs and other cytoskeletal components for their potential influence
      of mitochondrial movement as a test for activity and side effects.

PMID- 18636347
TI  - Identification of allelic polymorphism in the ovine leptin gene.
AB  - Leptin is an adipocyte-derived hormone/cytokine that influences the physiological
      control of numerous biological functions and links nutritional status with both
      neuroendocrine and immune functions. In livestock, variation in the leptin (LEP)
      gene has been characterized in cattle and pig, but it has not been reported in
      sheep. In this study, variation in the exon 3 coding sequence of the ovine LEP
      gene was investigated by polymerase chain reaction-single-strand conformational
      polymorphism (PCR-SSCP) analysis and DNA sequencing. Five novel SSCP patterns,
      representing five different sequences, were identified under a combination of two
      different electrophoresis conditions. Either one or two different sequences were
      detected in individual sheep and all the sequences identified shared high
      homology with the LEP sequences from a variety of species, suggesting that these
      sequences represent alleles of the ovine LEP gene. Four single nucleotide
      polymorphisms (SNPs) were detected, and three of these resulted in amino acid
      changes. Variation detected here might have an impact on leptin activity and
      function.

PMID- 18636348
TI  - [Understanding the planes of total mesorectal excision through surgical anatomy
      of pelvic fascia].
AB  - OBJECTIVE: To study the relationship of mesorectum with fasciae and nerves in the
      pelvic cavity and to specify the proper planes of dissection in total mesorectal
      excision. METHODS: Twenty-four pelvises (12 males and 12 females) harvested from
      cadavers were studied by dissection. RESULTS: There were three planes surrounding
      the rectum as the visceral fascia, vesicohypogastric fascia and parietal fascia.
      The pelvic plexus and its branches situated between the visceral fascia and the
      vesicohypogastric fascia. Pelvic splanchnic nerves and hypogastric nerves were
      observed between the visceral fascia and the parietal fascia. CONCLUSIONS: The
      posterior plane of total mesorectal excision lies between the visceral fascia and
      the parietal fascia. The lateral dissection should be conducted in a plane
      between the visceral fascia and the vesicohypogastric fascia. The proper planes
      for posterior and lateral resection can be identified by the hypogastric nerve
      and the pelvic plexus respectively.

PMID- 18636349
TI  - [Diagnosis and surgical treatment of colorectal cavernous hemangioma: a report of
      4 cases and review of Chinese literatures].
AB  - OBJECTIVE: To summarize the clinical features and surgical methods for colorectal
      cavernous hemangioma in China. METHODS: Data of 4 cases in Peking Union Medical
      College Hospital and 54 cases with colorectal cavernous hemangioma from 1979 to
      2006 reported in Chinese literatures were analyzed retrospectively, including
      clinic manifestations and surgery treatment. RESULTS: The incidence of male to
      female was 1.0:1.0, and 43.1% of the patients had their first onset of recurrent
      rectal bleeding in early childhood. Colonoscopy, rectal CT scan and MRI were the
      accurate methods for the diagnosis (100%). 91.4% of the patients had diffuse
      infiltrative lesions and 8.6% of the patients had localized lesions. 82.8% of the
      patients underwent surgical treatment while 3.5% of the patient did not received
      treatment. CONCLUSIONS: Colonoscopy is the first choice for the diagnosis of
      colorectal cavernous hemangioma. Local resection should be performed for the
      localized cavernous hemangioma. Sigmoid colon and rectum resection with coloanal
      anastomosis is suitable for the diffuse and infiltrative colorectal cavernous
      hemangioma.

PMID- 18636350
TI  - [Clinical value of screening hereditary nonpolyposis colorectal cancer in China
      with protocol recommended by NCCN guidelines].
AB  - OBJECTIVE: To investigate the effect of the protocol recommended by NCCN-2007 on
      the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) in China.
      METHODS: NCCN protocol consists of identifying HNPCC characteristics according to
      the revised Bethesda Guidelines,genetic counseling with immunohistochemistry and
      finally genetic testing. Four hundred and nineteen patients diagnosed as
      colorectal cancer from January 2002 to February 2006 were selected. The hMLH1 and
      hMSH2 immunostaining were implemented for 90 patients who fulfilled the revised
      Bethesda Guidelines, in whom 8 patients fulfilling the Amsterdam II (Criteria
      were classified as group A and the other 82 patients as group B. The frozen
      tissues were collected from patients who showed loss of hMLH1 or hMSH2 protein
      expression, then RNA was extracted, and RT-PCR and cDNA sequencing were adopted
      to detect the germline mutations of hMLH1 and hMSH2. RESULTS: Tumor tissues from
      18 patients showed loss of hMLH1 or hMSH2 protein expression (5 patients in group
      A and 13 in group B). Finally, 21 patients(8 in group A and 13 in group B showed
      loss expression of MMR protein) were diagnosed as HNPCC, including 2 cases of
      hMLH1 and 1 case of hMSH2 mutations. These 3 cases with cDNA mutations did not
      fulfill the Amsterdam II( Criteria, and were finally diagnosed as HNPCC.
      CONCLUSION: The protocol recommended by NCCN-2007 offers a useful approach to
      identify HNPCC patients,and reduces the possibility of missed diagnosis of HNPCC.

PMID- 18636351
TI  - [Evaluation of risk factors associated with local recurrence after radical
      resection of rectal carcinoma].
AB  - OBJECTIVE: To investigate the risk factors of local recurrence after radical
      resection of rectal carcinoma. METHODS: Clinical and follow-up data of 535
      patients with rectal carcinoma, received radical resection between August 1994
      and July 2004 in our department, were reviewed retrospectively. The association
      of clinicopathological factors and local recurrence was analyzed using Log-rank
      test. Cox multiple variate analysis was conducted to determine the independent
      risk factors. RESULTS: All the 535 rectal carcinoma patients underwent radical
      resections. Local recurrence occurred in 53 cases (9.9%), and distant metastasis
      co-occurred in 39 cases (7.3%). The time from the first operation to the
      recurrence was 4-54 months with a median of 12 months. The Log-rank test showed
      that the primary tumor site (P<0.01), differentiation(P<0.01), histological
      type(P=0.038), lymph node metastasis(P=0.023), Dukes staging(P=0.045), blood
      transfusion(P=0.001), and total mesorectum excision (TME)(P<0.001) were
      associated with the recurrence, but the operative style(P=0.908), invasive depth
      of primary tumor(P=0.735), massive pathological type(P=0.562), degree of
      surgeon(P=0.171) and post-operative chemotherapy (P=0.772) were not associated
      with the recurrence. Cox multiple variate analysis revealed that blood
      transfusion, primary tumor site, differentiation, lymph node metastasis, and TME
      principle were independent prognostic factors affecting local recurrence after
      radical resection of rectal cancer. CONCLUSIONS: Blood transfusion, low position
      of tumor, poor differentiation, lymph node metastasis are the risk factors
      associated with local recurrence in rectal cancer. Application of TME principle
      is the key point to decrease the local recurrence rate.

PMID- 18636352
TI  - [Clinical analysis of 98 cases of primary gastric lymphoma].
AB  - OBJECTIVE: To explore the clinical characteristics, diagnosis and treatment
      regimens for the primary gastric lymphoma (PGL). METHODS: The data of 98 PGL
      patients treated from January 1994 to December 2006 were collected and analyzed
      retrospectively. RESULTS: Abdominal pain was the common symptom of PGL. All the
      patients were at stage I or stage II, and the preoperative diagnosis rate was
      56.5%. The overall 1-, 3- and 5-year survival rates were 95.1%, 86.0% and 73.0%
      respectively. The 5-year survival rates of stage I and stage II patients were
      89.5% and 66.7% respectively, and the difference was significant. The 5-year
      survival rate of patients received operations was 77.2% and that without
      operation was 75.0%, the difference was not significant. CONCLUSIONS: The therapy
      based on chemotherapy is preferred for the treatment of PGL. In the cases of
      serious gastrointestinal complications, indefinite pathological diagnosis or non
      effective chemotherapy, operations should be considered.

PMID- 18636353
TI  - [Endoscopic self-expanded metal stent for gastric outlet obstruction:a ten-year
      experience].
AB  - OBJECTIVE: To evaluate the efficacy of endoscopic self-expanded metal stent for
      the treatment of gastric outlet obstruction. METHODS: Fifty-six cases of gastric
      outlet obstruction, collected from March 1999 to January 2008, were treated by
      endoscopic self-expanded metal stents. The success rate, complication rate and
      survival were evaluated. RESULTS: Among the 56 cases, the male to female ratio
      was 33 to 23, and the average age was [65+/-14 (24-86)] years. Seventeen cases
      were gastric cancer, 4 duodenal carcinoma, 7 peri-ampulla carcinoma, 13
      metastasis cancer and 15 presented recurrence after operations. The success rate
      of stent implantation was 98.2% (55/56). Forty-nine cases (87.5%) could eat
      liquid food 1-3 days after operations and eat semifluid food 4-9 days later.
      Forty-two cases (76.4%)could eat normal food after 10-16 days. The main
      complications included 14.5% of cases with pain, 1.8% with stent shift, 25.5%
      with bleeding and no one with perforation. Until January 20, 2008, 53 cases
      (96.4%) had been followed up. The mean survival time was [139+/-15 (14-332)]
      days, and the median survival time was 135 days. The re-stenosis rate was 5.7%,
      including 3 cases, happened in 143, 158 and 190 days after the operations
      respectively, and was successfully treated by second stent implantation.
      CONCLUSION: Endoscopic implantation of self-expanded metal stent is a micro
      invasive, safe, effective method for the treatment of gastric outlet obstruction.

PMID- 18636354
TI  - [Application of somatostatin combined with oral vancomycin in the treatment of
      intestinal obstruction after liver transplantation].
AB  - OBJECTIVE: To investigate the effect of somatostatin combined with oral
      vancomycin in the treatment of intestinal obstruction after liver
      transplantation. METHODS: Fifty-eight cases of intestinal obstruction after liver
      transplantation from Jan. 2005 to Dec. 2006 were divided into two groups: Group A
      (from Jan. 2005 to Dec. 2005) received traditional treatment, including
      fasting,gastrointestinal decompression, maintaining electrolyte and acid-base
      balance, enteral and parenteral nutrition support and antibiotics; Group B (from
      Jan. 2006 to Dec. 2006) received somatostatin combined oral vancomycin in
      addition to the above mentioned traditional treatment. RESULTS: Fifty-eight cases
      out of 441 patients (13%) suffered from intestinal obstruction after liver
      transplantation. Group B had a better outcome as compared with Group A, including
      a quick recovery of flatus and stool, [(7.1+/-2.0) d and (8.4+/-2.4) d vs (9.1+/
      3.0) d and (10.8+/-3.4) d] (P<0.05), less amount of gastric drainage [(298+/-58)
      ml/d vs (485+/-106) ml/d](P<0.05). The rate of intestinal flora imbalance in
      Group B was 55%, which was significantly less than the 77% in Group A(P<0.05).
      CONCLUSION: The application of somatostatin combined with oral vancomycin can
      improve the symptoms of intestinal obstruction after liver transplantation and
      decrease the rate of intestinal flora imbalance.

PMID- 18636355
TI  - [Application of magnetic resonance imaging in the diagnosis of complex anal
      fistula].
AB  - OBJECTIVE: To evaluate the value of magnetic resonance imaging (MRI) in the
      diagnosis of complex anal fistula. METHODS: The preoperative digital examination
      and MRI with the phased-array coil were implemented for 28 patients who were
      clinically suspected with complex anal fistula. The final diagnosis were based on
      surgical findings. Outcomes of MRI and digital examination were compared with
      surgical results. RESULTS: Twenty-five patients were diagnosed as complex anal
      fistula, 1 presacral cyst and 2 chronic anorectal fistula combined with perianal
      mucinous adenocarcinoma. All the patients were correctly diagnosed by MRI,while
      the patients with presacral cyst and perianal mucinous adenocarcinoma could not
      be diagnosed correctly by digital examination. According to the Parks
      classification, 3 patients were suffered from trans-sphincteric fistula, 10
      intersphincteric, 5 supra- sphincteric and 7 extra-sphincteric. The diagnosis
      rates of the internal opening with digital examination and MRI were 48% and 84%,
      the rates of the primary tract were 76% and 100%, and the rates of the secondary
      extensions were 57.9% and 94.7% respectively. The differences in detection of
      internal opening, primary tract and secondary extensions between MRI and digital
      examination were significant (P<0.01). CONCLUSION: MRI with the phased-array coil
      can correctly orient the internal opening and direction of the complex anal
      fistula, and find the relationship between anorectal sphincters and the complex
      fistula.

PMID- 18636356
TI  - [Study of enteral nutrients transport in intestinal hypoperfused rat model].
AB  - OBJECTIVE: To study the transport of glutamine and glucose, expression of their
      transporters and tissue morphology in intestinal hypoperfusion. METHODS: Sprague
      Dawley rats were randomized to receive 60 min of intestinal hypoperfusion
      (superior mesenteric artery clamp) or serve as normoxic controls (celiotomy
      only). At the same time, jejunal loops were randomized to receive in situ
      perfusion of mannitol,glucose,or glutamine.Intestinal brush border membrane
      vesicles (BBMV) were prepared by calcium precipitation. Sodium-dependent uptake
      of glucose and glutamine into BBMV were quantitated by rapid mixing and
      filtration. Histologic examination and immunohistochemistry were performed by
      pathologists blinded to the groups. RESULTS: When compared with the control
      group, tissue lactate concentration of the hypoperfused group increased
      significantly (4.9+/-0.3 vs 3.1+/-0.2), especially in the glucose perfused groups
      (P<0.01). Transport and transporters of glucose in brush border, but not
      glutamine, decreased during hypoperfusion [(76+/-10) pmol d mg(-1) d 10 s(-1) vs
      (290+/-13)pmol d mg(-1) d 10 s(-1)]. Tissue structural damage was most severe in
      glucose perfused groups during hypoperfusion. CONCLUSION: Transport and
      expression of transporters of glucose and glutamine in enteral nutrition are
      differently regulated under conditions of trauma and stress.

PMID- 18636357
TI  - [Establishment of nude mice liver metastatic model of human primary malignant
      melanoma of the small intestine].
AB  - OBJECTIVE: To provide ideal animal models for exploring pathogenesis and
      experimental therapy of primary malignant melanoma of the small intestine.
      METHODS: The histologically intact primary and liver metastatic fragments derived
      from surgical specimens of one patient with metastatic malignant melanoma of the
      small intestine were orthotopically implanted in the small intestinal mucous
      layer of nude mice. The take rate, invasion and liver metastasis were observed.
      Morphology (light microscopy, electron microscopy), immunophenotype analysis,
      flow cytometry and karyotype analysis were applied for the original human tumors
      and the transplanted tumors. RESULTS: The primary and liver metastatic fragments
      of malignant melanoma of the small intestine were successfully implanted in nude
      mice. After continuous passages in nude mice,an orthotopic model of human primary
      malignant melanoma of the small intestine(from the primary focus)in nude mice
      (termed HSIM-0501) and a liver metastatic model of human primary malignant
      melanoma of the small intestine (from the liver metastatic focus) in nude mice
      (termed HSIM-0502) were established. Histological examination of transplanted
      tumors revealed high-grade melanoma. S-100 protein and HMB45 were positive.
      Massive melanin granules and melanin complex were seen in cytoplasm of tumor
      cells.Chromosomal modal number was between 55 and 59. DNA index (DI) was 1.49
      1.61, representing heteroploid. HSIM-0501 and HSIM-0502 were maintained for 25
      and 27 passages in nude mice respectively. Three hundred and seventeen nude mice
      were used for transplantation. Both the take rate after transplantation and
      resuscitation rate of liquid nitrogen cryopreservation were 100%. HSIM-0501
      exhibited 46.2% liver metastasis and 36.7% lymph node metastases. In HSIM-0502,
      both liver and lymph node metastases were 100%.The transplanted tumors
      autonomically and invasively grew in the small intestines of nude mice and
      hematogenous metastasis, lymph node metastasis and celiac planting metastasis
      occurred. CONCLUSION: Two nude mice liver metastatic models of human primary
      malignant melanoma of the small intestine are successfully established, which
      provide ideal animal models for the research of pathogenesis,metastasis biology
      and anti-metastatic experimental therapy of primary malignant melanoma of the
      small intestine.

PMID- 18636358
TI  - [Expression of candidate tumor suppressor gene N-Myc downstream-regulated gene 2
      in colon cancer].
AB  - OBJECTIVE: To analyze the expression level of candidate tumor suppressor gene N
      Myc downstream-regulated gene 2 (NDRG2) in human colon cancer. METHODS: Thirty
      samples of colon cancer tissues with matched normal colon tissues were collected.
      The NDRG2 mRNA level was detected by semi-quantitive RT-PCR and the NDRG2 protein
      level was examined by Western blot and immunohistochemistry. RESULTS: Twelve
      samples of colon cancer tissues had low NDRG2 mRNA level and low protein level.
      The positive rates of NDRG2 in normal tissues and the tumorous colon tissues were
      90.0%(27/30) and 53.3%(16/30) by immunohistochemistry respectively. There was a
      significant difference between two groups (P<0.05). The NDRG2 expression was not
      correlated with age, sex, metastasis of lymph node, depth of infiltration, as
      well as the Dukes staging(P>0.05), while it was correlated to the histology
      grading. The positive rate of NDRG2 in the well- and moderate-differentiation
      group was higher than that in the poor-differentiation group(P<0.05). CONCLUSION:
      The expression of NDRG2 is low in some colon cancer tissues, which indicates that
      the low level of NDRG2 expression may be engaged in the development of colon
      cancer.

PMID- 18636359
TI  - [Study of germline mutation of hMSH2, hMSH6 and hMLH1 and methylation of hMLH1 in
      microsatellite instability colorectal cancer].
AB  - OBJECTIVE: To study the characteristics of germline mutations of hMLH1, hMSH2 and
      hMSH6 and promoter methylation status of MLH1 in patients with MSI colorectal
      cancer. METHODS: Sequence analysis of germline mutation and promoter methylation
      of MLH1 in 34 prospective collected patients with MSI colorectal cancer were
      performed. RESULTS: Nineteen out of 34 patients with MSI colorectal cancer were
      detected with hypermethylation of MLH1,which accounted for 55.9%. 73.7% MSI-H
      colorectal cancer cases and 33.3% MSI-L colorectal cancer cases were detected
      with hypermethylation of MLH1 and the difference was significant. Eight germline
      mutations were found, including 3 MSH6 mutations and 5 MSH2 mutations.
      CONCLUSION: There are some different characteristics of the germline mutations of
      hMLH1, hMSH2 and hMSH6 and promoter methylation of MLH1 in Chinese MSI colorectal
      patients.

PMID- 18636360
TI  - [Vascular endothelial growth factor D promoting the growth of lymphatic vessel in
      gastric carcinoma].
AB  - OBJECTIVE: To investigate the relationship between vascular endothelial growth
      factor D (VEGF-D) and metastasis of lymphatic vessel in gastric carcinoma.
      METHODS: The human VEGF-D cDNA was amplified from total RNA isolated from human
      normal gastric tissue, then it was inserted into T-A clone plasmid and subcloned
      into pEGFP eukaryotic expression vector. After the full-length sequence expected
      was confirmed by enzymatic digestion and sequencing,the human gastric carcinoma
      cell line SGC7901, which expressed a low level of VEGF-D, was transfected with
      the pEGFP/VEGF-D expression vector. Stable SGC7901 clones with high expression of
      VEGF-D were selected in vitro with G418, which were then combined and
      subcutaneously injected into nude mice to observe the density and morphology of
      lymphatic vessel. The outcomes were later compared with those of SGC7901 cells
      transfected with null vector(pEGFP) by immunostaining with a specific antibody
      LYVE-1. RESULTS: The average weight of tumors in the pEGFP group (1.13+/-0.40) g
      at day 35, was significantly lower than that in the pEGFP/VEGF-D group (2.24+/
      0.82)g (P<0.05). The lymphatic vessel density (LVD) in the pEGFP group (2.89+/
      1.32) was significantly lower than that in the pEGFP/VEGF-D group (5.74+/
      1.30)(P<0.01). There were dilated functional lymphatic vessels around the tumor
      margin. CONCLUSION: VEGF-D may promote the growth and metastasis of tumor in
      gastric carcinoma by increasing the growth of lymphatic vessels.

PMID- 18636361
TI  - [Correlation of vascular endothelial growth factor D, microlymphatic density and
      microvessel density with development and metastasis of rectal cancer].
AB  - OBJECTIVE: To investigate the correlation of vascular endothelial growth factor D
      (VEGF-D) expression, microlymphatic density (MLD) and microvessel density (MVD)
      levels with the development and metastasis of rectal cancer. METHODS: Eighty
      specimens from resected middle-lower rectal cancer diagnosed by pathology were
      examined by immunohistochemistry for VEGF-D,MLD and MVD. Simultaneously, 40
      biopsy specimens from rectal polyps and 80 specimens from normal rectal tissue
      were examined as controls. Correlation between the expression of above three
      factors and the tumor size, gross morphology, histological type, metastasis,
      differentiation grade, infiltration depth, Dukes stage, lymph node metastasis and
      long-distance metastasis before operation were investigated with Spearman method.
      RESULTS: (1) Positive expression rate of VEGF-D was 55 % (44/80) in rectal
      cancer, and zero in rectal polyps and normal rectal tissues. The expression of
      VEGF-D in rectal cancer was significantly higher than that in rectal polyps and
      normal rectal tissues(P<0.05). MLD was significantly higher in rectal cancer
      (2.80+/-1.31) than that in rectal polyps (0.50+/-0.72) and normal rectal
      tissues(0.25+/-0.44)(P<0.05).Meanwhile MVD was significantly higher in rectal
      cancer (80.10+/-23.18) than that in rectal polyps (27.00+/-11.01) and normal
      rectal tissues (10.45+/-5.34) (P<0.05). (2) VEGF-D, MLD and MVD were positively
      correlated with lymph node metastasis and long-distance metastasis before
      operation (P<0.05). (3) VEGF-D was positively correlated with MLD (P<0.05) and
      MLD was positively correlated with MVD as well(P<0.05). CONCLUSIONS:
      Lymphangiogenesis exists in rectal cancer tissues. VEGF-D and MLD can be used as
      good predictors of lymphangiogenesis and they are the important factors affecting
      biological behavior of rectal cancer. Lymphangiogenesis and angiogenesis may have
      a cooperative function in the development of rectal cancer.

PMID- 18636362
TI  - [Status and clinical analysis of c-kit and PDGFRA mutations in the
      gastrointestinal stromal tumors].
AB  - OBJECTIVE: To investigate the status of c-kit and PDGFRA mutations in the
      gastrointestinal stromal tumors (GIST) and explore the relationship between the
      mutations and the clinical features. METHODS: One hundred and forty-one cases
      were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9,11,13, 17
      of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct
      sequencing. The relations of clinical features and mutational status were
      analyzed with statistical tools in this study. RESULTS: Among the 141 GISTs, c
      kit mutations were identified in 76.6% (108/141): 70.2% (99/141) involving exon
      11, 5.7% (8/141) involving exon 9, 0.7% (1/141) involving exon 13 and no mutation
      detected in exon 17. The gene mutations were mostly heterogeneous. The c-kit exon
      11 mutational format included deletion (65.7%), point mutation (24.2%) and insert
      duplications(10.1%).The mutations clustered in the classic "hot spot" at the 5'
      end of the exon mostly heterogeneous and the second "hot spot" were internal
      tandem duplications (ITD) at the 3' end of the exon. PDGFRA mutations were
      totally identified in 12.1%(4/33) of no-c-kit-mutation GISTs and 40%(4/10) of
      CD117-negative GISTs: all involving exon 18 with the mutations D842V. With the
      analysis between clinical features and mutation status, the significant
      difference of gene mutation rate in the different primary tumor organs
      (chi(2)=7.229, P=0.027, chi(2)=7.000,P=0.03) and no significant differences
      between the groups of age,gender,tumor size,mitotic rate,grade of malignant
      potential were found. CONCLUSION: Most GISTs have the c-kit or PDGFRA gene
      mutation. There are significant difference between mutation and primary tumor
      organ.

PMID- 18636363
TI  - [Effect of Endostatin and SU6668 combined with 5-FU on human colon cancer
      xenograft in nude mice].
AB  - OBJECTIVE: To investigate the effect of Endostatin and SU6668 combined with 5-FU
      on the growth and metastasis of human colon cancer in vivo and its mechanism.
      METHODS: Metastatic model of human colon cancer was established by orthotopic
      implantation of human tumor tissue into colon wall of nude mice. Twelve days
      later, mice were randomly divided into saline water control, Endostatin, SU6668,
      Endostatin plus SU6668, and Endostatin plus SU6668 and 5-FU groups,
      intraperitoneal injected respectively every day for four weeks. Six weeks after
      implication, the tumor weight, inhibition rates, intratumoral microvessel density
      (MVD) and metastasis were evaluated after the mice were sacrificed. RESULTS:
      Compared with the control, tumor growth was significantly inhibited in mice
      treated respectively with Endostatin, SU6668, Endostatin plus SU6668 and
      Endostatin plus SU6668 and 5-FU with an inhibition rate of 0, 64.9%, 63.5%, 76.4%
      and 88.2% respectively,and MVD decreased significantly in treated groups
      [(18.10+/-5.65) vs (2.75+/-0.75), (3.17+/-0.58), (0.94+/-0.42) and (0.36+/
      0.45)]. The incidences of peritoneal and region lymph node metastases were
      significantly inhibited in Endostatin, SU6668, Endostatin plus SU6668 and
      Endostatin plus SU6668 and 5-FU (90% vs 16.7%, 25%, 0 and 0; 90% vs 0, 0, 0 and
      0). The growth and metastasis of human colon cancer implanted in nude mice were
      significantly inhibited in Endostatin, SU6668, Endostatin plus SU6668, and
      Endostatin plus SU6668 and 5-FU, and the effect of Endostatin plus SU6668 and 5
      FU was the most obviously. CONCLUSION: Endostatin plus SU6668 and 5-FU has strong
      inhibitory effect both on tumor growth and metastasis of human colon cancer.

PMID- 18636364
TI  - [Promoter methylation and expression of Runx3 gene in gastric cancer].
AB  - OBJECTIVE: To analyze the relationships among the aberrant methylation of Runx3
      gene promoter, the Runx3 protein expression and clinicopathological features in
      gastric cancer. METHODS: Methylation specific PCR was used to measure the
      promoter methylation status of Runx3 gene in tumor and the adjacent normal
      mucosal tissues from 40 patients with gastric cancer. Protein expression of Runx3
      was measured by immunohistochemistry. RESULTS: The frequency of promoter
      methylation of Runx3 gene in gastric cancer tissue(55.0%) was significantly
      higher compared to the adjacent normal tissues (12.5%)(P<0.01). The positive rate
      of protein expression of Runx3 in gastric cancer tissue(37.5%) was significantly
      lower compared to the adjacent normal tissues (100%). There was marked
      association between hypermethylation and negative protein expression (P<0.05).
      The frequency of Runx3 promoter methylation was associated with histological
      type, N grade, and tumor stage. CONCLUSION: The promoter hypermethylation is a
      main mechanism of reduced or loss expression of Runx3 gene, which may provide
      molecular diagnosis and stage evaluation of gastric cancer.

PMID- 18636365
TI  - Organophosphorus pesticide residues in Greek virgin olive oil: levels, dietary
      intake and risk assessment.
AB  - The occurrence of organophosphorus pesticide (OPs) and their metabolite residues
      was investigated in 167 samples of Greek virgin olive oil during a 2-year (2004
      2005) sampling campaign. A total of 30.5% of samples contained detectable
      residues, although only one sample contained dimethoate residues above the
      maximum residue limit. Among the seven detected OPs, fenthion and fenthion
      sulfoxide residues were detected in 10.8 and 14.4% of the samples, respectively,
      at levels of 0.003-0.61 mg kg(-1). Dimethoate was detected in 10.2% of the
      samples at 0.003-0.057 mg kg(-1). The acute dietary risk assessment was
      undertaken by determining the national estimated short-term intake (NESTI); for
      chronic dietary risk assessment, the national theoretical maximum daily intake
      (NTMDI) and national estimated daily intake (NEDI) were calculated. The estimated
      intakes (NESTI and NEDI) of each pesticide were <7 and <0.86% of the
      corresponding acute reference doses (ARfDs) and acceptable daily intakes (ADIs),
      respectively. A cumulative risk assessment was performed using the hazard index
      (HI) and toxicity equivalence factor (TEF), taking into account that OPs share
      the same toxicological mechanism. The determined HI and TEF values were found to
      represent only a small portion of the respective ADIs or ARfDs. These results
      indicate that there is neither acute nor chronic risk for the Greek population
      through olive oil consumption.

PMID- 18636366
TI  - Angiotensin-converting enzyme inhibition and free-radical scavenging properties
      of cationic peptides derived from soybean protein hydrolysates.
AB  - Soybean protein isolate was hydrolyzed consecutively with pepsin and pancreatin
      followed by separation of the digest on a SP-Sepharose column to obtain
      angiotensin-converting enzyme (ACE)-inhibitory fractions. Three of the five
      fractions obtained inhibited ACE activity, with values of the concentration of
      hydrolysate fraction that inhibited 50% of ACE activity of 1.09, 0.42, and 0.25
      mg/ml for fractions 2, 3, and 4, respectively. Kinetic analysis showed that
      fractions 2, 3, and 4 are non-competitive, competitive and mixed inhibitors of
      ACE, respectively. Fluorescence emission of ACE was quenched along with a red
      shift in wavelength of emission maxima in the presence of the protein hydrolysate
      fractions. Fraction 3 was the most potent free-radical scavenger, while fraction
      4 had almost no scavenging effect. We concluded that fraction 3 had the most
      potential to be used as a bioactive ingredient because of its strong ACE
      inhibitory and free-radical scavenging properties.

PMID- 18636367
TI  - An investigation into the bioaccessibility of potassium in unprocessed fruits and
      vegetables.
AB  - Epidemiological studies and clinical trials have consistently shown an inverse
      association between potassium intake and blood pressure. As a means of raising
      potassium intake within the UK population, an increase in the consumption of
      fruits and vegetables is strongly advocated. The aim of this study was to
      determine the bioaccessibility of potassium in these foods. A 10-day crossover
      feeding trial was performed on 11 healthy volunteers. For 5 days a diet providing
      most of the potassium in the form of unprocessed fruits and vegetables was
      followed by a diet in which the potassium was believed to be almost wholly
      bioaccessible, being derived from animal foods and fruit juices. The potassium
      and sodium of the diets and the urine were determined by chemical analysis: 96.3%
      of the potassium in the 'high bioaccessible diet' was recovered in the urine,
      compared with 76.8% from the diet rich in fruits and vegetables. This difference
      is attributed to the cellular structure of plant foods. The relatively poor
      bioaccessibility of potassium diminishes the perceived nutritive value of these
      foods with regard to potassium intake.

PMID- 18636368
TI  - Trocheliophorin: a novel rearranged sesquiterpenoid from the Indian Ocean soft
      coral Sarcophyton trocheliophorum.
AB  - A novel rearranged sesquiterpenoid, trocheliophorin (1) has been isolated from
      the soft coral Sarcophyton trocheliophorum besides the known compounds,
      sarcophytin, methyl arachidonate, and two polyhydroxy steroids (24S)-24
      methylcholestane-3beta,5alpha,6beta,25-tetrol-25-monoacetate and (24S)-24
      methylcholestane-3beta,5alpha,6beta,25-tetrol. The structure of the new
      sesquiterpenoid was elucidated by a study of its spectral data.

PMID- 18636369
TI  - Two new alkyl glycosides from Clerodendranthus spicatus.
AB  - Two new alkyl glycosides, 3-O-beta-D-apifuranosyl-(1 --> 6)-O-beta-D
      glucopyranosyl-(3S)-oct-1-en-3-ol (1, clerspide A) and 3-O-beta-D-apifuranosyl-(1
      --> 6)-[beta-D-xylopyranosyl-(1 --> 2)]-O-beta-D-glucopyranosyl-(3S)-oct-1-en-3
      ol (2, clerspide B), have been isolated from the whole plants of Clerodendranthus
      spicatus (Labiatae). Their structures were established on the basis of
      spectroscopic analyses and chemical method.

PMID- 18636370
TI  - A new hTopo I isomerase inhibitor produced by a mangrove endophytic fungus no.
      2240.
AB  - A new hTopo I isomerase inhibitor, (+)-3,3',7,7',8,8'-hexahydroxy-5,5'
      dimethylbianthraquinone (2240A), was isolated from the mangrove endophytic fungus
      no. 2240 collected from an estuarine mangrove at the South China Sea coast. Its
      structure was elucidated by spectral analyses including two-dimensional NMR, HR
      EI-MS, IR, and UV. The hTopo I isomerase inhibition experiment showed that 2240A
      (1) possessed strong inhibiting activity. When its inhibition concentration was
      4.65 micromol/l, its percent inhibition rate was 59.1%, while the lowest
      inhibition concentration of the positive control camptothecin was 1.00 x 10(3)
      micromol/l.

PMID- 18636371
TI  - Flavonoids from Galium verum L.
AB  - Two new flavonoids, compounds 1 and 2, together with seven known flavonoids, were
      isolated from Galium verum L. Their structures were elucidated as diosmetin 7-O
      alpha-l-rhamnopyranosyl-(1-2)-[beta-d-xylopyranosyl-(1-6)]-beta-d-glucopyranoside
      (1) and 3,5,7,3',4',3'',5'',7'',3''',4'''-decahydroxyl-[8-CH(2)-8'']-biflavone
      (2) by chemical methods and spectroscopic analyses. Compounds 3 and 4 were
      isolated from the genus Galium for the first time.

PMID- 18636372
TI  - A study on the chemical constituents of Veratrum nigrum L. processed by rice
      vinegar.
AB  - One new steroid alkaloid, 12beta-hydroxylveratroylzygadenine (1) and four known
      compounds, verdine (2), jervine (3), veramarine (4), and veratroylzygadenine (5),
      have been isolated from the roots and rhizomes of Veratrum nigrum L. processed by
      rice vinegar. Their structures were established through a combined analysis of
      physicochemical properties and spectroscopic evidence. The assay results revealed
      that compounds 1, 4, and 5 exhibited cell toxicity against human HL-60 cells with
      IC50 values 52.67, 52.90, and 56.51 micromol/l, respectively.

PMID- 18636373
TI  - Two new metabolites from the mangrove endophytic fungus no. 2106.
AB  - Two new metabolites, named no. 2106 A (1) and cyclo-(N-MeVal-N-MeAla) (2), have
      been produced by the endophytic fungus no. 2106 isolated from the seeds of the
      mangrove Avicennia marina in Hong Kong. The structures were elucidated by 2D NMR,
      HR-MS, and X-ray diffraction analyses.

PMID- 18636374
TI  - Preparation and antitussive, expectorant, and antiasthmatic activities of
      verticinone's derivatives.
AB  - To prepare verticinone derivatives with significant antitussive, expectorant, and
      antiasthmatic activities, the compounds 3beta-acetylverticinone (1), 3
      ketoverticinone (2), 3beta-benzoylverticinone (3), 3beta-propionylverticinone
      (4), 3beta-butyrylverticinone (5), and 3beta-butoxycarbonylverticinone (6) have
      been prepared. All of these are new compounds. Among them, 1-6 exhibited potent
      antitussive and expectorant activities; 1 and 3-6 displayed various antiasthmatic
      activities. The antitussive activity of 1-6, the expectorant activity of 1-2 and
      4-6, and the antiasthmatic activity of 1 are higher than those of verticinone.
      The results demonstrated that 1 had dominant biological activities, suggesting
      that it would be a potential antitussive, expectorant, and antiasthmatic agent.

PMID- 18636375
TI  - Antifungal stilbenoids from Stemona japonica.
AB  - Three new dihydrostilbenes, stilbostemins P-R (1-3), and a new
      dihydrophenanthrene, stemanthrene G (4), were isolated from the roots of Stemona
      japonica together with three known bibenzyls, 3,5-dihydroxy-2'-methoxy bibenzyl
      (5), 3,3'-dihydroxy-2,5'-dimethoxy bibenzyl (6), and 3,5,2'-trihydroxy-4-methyl
      bibenzyl (7). Their structures were elucidated by spectroscopic analyses.
      Compounds 5 and 6 exhibited strong antifungal activities against Candida
      albicans.

PMID- 18636376
TI  - Poriacosones A and B: two new lanostane triterpenoids from Poria cocos.
AB  - Two new lanostane triterpenoids, poriacosones A (8) and B (9), together with
      eight known compounds were isolated from the sclerotia of Poria cocos (Schw.)
      Wolf (Polyporaceae), and identified by spectroscopic analysis, including IR, UV,
      CD, ESI-TOF-MS, HR-SIMS, 1D-, and 2D-NMR spectra. The structures of the new
      compounds were established as 3alpha,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien
      21-oic acid (8) and 3beta,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid
      (9).

PMID- 18636377
TI  - Two novel bibenzyls from Dendrobium trigonopus.
AB  - Two novel bibenzyl trigonopols A (1) and B (2), together with seven known
      compounds, gigantol (3), tristin (4), moscatin (5), hircinol (6), naringenin (7),
      3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-ol (8), and ( - )-syringaresinol (9),
      have been isolated from the stems of Dendrobium trigonopus, of which compounds 6,
      8, and 9 were isolated for the first time from this species. The structures of
      two new compounds were elucidated as threo-22-(17-hydroxyl-9-(3-hydroxyl-4
      methoxy-phenethyl)-13,16,18-trimethoxy-21H-benzo[c]chromen-21-yl)ethane-22, 23
      diol (1) and 9-(4-hydroxyl-3-methoxy-phenethyl)-17-(21-hydroxyl-20-methoxy
      phenyl)chroman-11, 16-diol (2) on the basis of spectroscopic methods. Trigonopol
      A was found to exhibit antiplatelet aggregation activity in vitro with 67.55%
      inhibitory ration at 1.4337 x 10(- 3) M.

PMID- 18636378
TI  - Chemical constituents from Clerodendron serratum.
AB  - A new compound, serratin, was isolated from the essential oil of Clerodendron
      serratum along with lupeol. The structure of the compound has been elucidated on
      the basis of chemical analysis and spectroscopic methods including IR, MS, and
      NMR techniques.

PMID- 18636379
TI  - Four new alkaloids from Polyalthia nemoralis (Annonaceae).
AB  - Four new alkaloids, polynemoralines A (1), B (2), C (3), and D (4), were isolated
      from the branches and leaves of Polyalthia nemoralis A DC. The structures of 1-4
      were elucidated mainly on the basis of spectroscopic methods. The structure of 4
      was confirmed by X-ray diffraction analysis.

PMID- 18636380
TI  - Xanthone glycosides from herbs of Polygala hongkongensis Hemsl and their
      antioxidant activities.
AB  - Two new xanthone O-glycosides, polyhongkongenosides A (1) and B (2), together
      with four known xanthone glycosides, were isolated from the herbs of Polygala
      hongkongensis Hemsl. Their structures were elucidated on the basis of UV, IR,
      NMR, and MS spectral data. The antioxidant in vitro activities of 1-6 were
      determined by the scavenging activities against 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radicals and hydroxyl radicals and their reductive activities to Fe3+.
      Mangiferin, one of the four known xanthone glycosides, showed potential
      scavenging effect on DPPH and hydroxy radicals and reductive activity to Fe3+
      with IC50 values of 4.7, 13.9, 23.7 microM, respectively.

PMID- 18636381
TI  - Two new C21 steroidal glycosides from Cynanchum wallichii Wight.
AB  - Two new C21 steroidal glycosides, characterized with caudatin as the aglycone
      moiety and 2,6-dideoxy-pyranoses as component sugars, have been isolated from the
      roots of Cynanchum wallichii Wight. Their structures were elucidated as caudatin
      3-O-beta-D-cymaropyranosyl-(1 --> 4)-beta-d-digitoxopyranoside (1) and caudatin-3
      O-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranoside (2) by spectroscopic
      evidence.

PMID- 18636382
TI  - Terpenoids from the tuber of Cremastra appendiculata.
AB  - Two new terpenoids including a cadinane sesquiterpene (1), and an ent-kaurane
      diterpene diglycoside (2), together with a known triterpene containing 32 carbons
      (3), have been isolated from the ethanolic extract of Cremastra appendiculata.
      Their structures were established by the spectroscopic methods including the IR,
      MS, 1D-, and 2D-NMR experiments as ( - )-cadin-4,10(15)-dien-11-oic acid (1), ( -
      )-ent-12beta-hydroxykaur-16-en-19-oic acid, 19-O-beta-D-xylopyranosyl-(1 --> 6)-O
      beta-D-glucopyranoside (2), and (+)-24,24-dimethyl-25,32-cyclo-5alpha-lanosta
      9(11)-en-3beta-ol (3). Compounds 1-3 were evaluated against several human cancer
      cell lines. Compound 3 showed in vitro-selective cytotoxicity against human
      breast cancer cell lines (MCF-7) with an IC50 of 3.18 microM, but 1 and 2 were
      inactive (IC50>10 microg/ml).

PMID- 18636383
TI  - Three new triterpenes from the roots of Rhus javanica L. var. roxburghiana.
AB  - Three new triterpenes, lantabetulal (1), lantanolal (2), and lantanolol (3) along
      with lantabetulic acid (4) and lantanolic acid (5) were isolated from the roots
      of Rhus javanica L. var. roxburghiana. The structural assignments of all these
      compounds were carried out by their spectroscopic analysis.

PMID- 18636384
TI  - Chemical constituents from Abutilon indicum.
AB  - The investigation on the chemical constituents of the whole plant of Abutilon
      indicum has resulted in the isolation of two new compounds, abutilin A (1) and
      (R)-N-(1'-methoxycarbonyl-2'-phenylethyl)-4-hydroxybenzamide (2), as well as 28
      known compounds. The structures of the two new compounds were established on the
      basis of the spectroscopic analysis, and the known compounds were identified by
      comparison of their spectroscopic and physical data with those reported in the
      literature.

PMID- 18636387
TI  - Research issues underlying the four-lab study: integrated disinfection by
      products mixtures research.
AB  - Chemical disinfection of drinking water is a major public health triumph of the
      20th century, resulting in significant decreases in morbidity and mortality from
      waterborne diseases. Disinfection by-products (DBP) are chemicals formed by the
      reaction of oxidizing disinfectants with inorganic and organic materials in the
      source water. To address potential health concerns that cannot be answered
      directly by toxicological research on individual DBPs or defined DBP mixtures,
      scientists residing within the various organizations of the U.S. Environmental
      Protection Agency's Office of Research and Development (the National Health and
      Environmental Effects Research Laboratory, the National Risk Management Research
      Laboratory, the National Exposure Research Laboratory, and the National Center
      for Environmental Assessment) engaged in joint investigation of environmentally
      realistic complex mixtures of DBP. Research on complex mixtures of DBP is
      motivated by three factors: (a) DBP exposure is ubiquitous to all segments of the
      population; (b) some positive epidemiologic studies are suggestive of potential
      developmental, reproductive, or carcinogenic health effects in humans exposed to
      DBP; and (c) significant amounts of the material that makes up the total organic
      halide portion of the DBP have not been identified. The goal of the Integrated
      Disinfection Byproducts Mixtures Research Project (the 4Lab Study) is provision
      of sound, defensible, experimental data on environmentally relevant mixtures of
      DBP and an improved estimation of the potential health risks associated with
      exposure to the mixtures of DBP formed during disinfection of drinking water. A
      phased research plan was developed and implemented. The present series of
      articles provides the results from the first series of experiments.

PMID- 18636388
TI  - Integrated disinfection by-products mixtures research: disinfection of drinking
      waters by chlorination and ozonation/postchlorination treatment scenarios.
AB  - This article describes disinfection of the same source water by two commonly used
      disinfection treatment scenarios for purposes of subsequent concentration,
      chemical analysis, and toxicological evaluation. Accompanying articles in this
      issue of the Journal of Toxicology and Environmental Health describe
      concentration of these finished waters by reverse osmosis techniques, chemical
      characterization of the resulting disinfection by-product (DBP) concentrates, in
      vivo and in vitro toxicological results, and risk assessment methods developed to
      analyze data from this project. This project, called the "Four Lab Study,"
      involved participation of scientists from four laboratories/centers of the U.S.
      Environmental Protection Agency Office of Research and Development as well as
      extramural collaborators from the water industry and academia. One of the two
      finished waters was prepared by conventional treatment and disinfected by
      chlorination. The other finished water was also prepared by conventional
      treatment and disinfected by ozonation followed by chlorination
      (ozonation/postchlorination). Chlorination conditions of dose, time and
      temperature were similar for both treatment scenarios, allowing for a comparison.
      Both finished waters had acceptably low levels of particulates and bacteria,
      representative pH and chlorine levels, and contained numerous DBP. Known effects
      of ozonation were observed in that, relative to the water that was chlorinated
      only, the ozonated/postchlorinated water had lower concentrations of total
      organic halogen, trihalomethanes (THM), haloacetic acids (HAA), and higher
      concentrations of bromate, and aldehydes.

PMID- 18636389
TI  - Integrated disinfection by-products mixtures research: concentration by reverse
      osmosis membrane techniques of disinfection by-products from water disinfected by
      chlorination and ozonation/postchlorination.
AB  - To conduct the health-effect studies described in subsequent articles in this
      series, concentrated aqueous mixtures of disinfection by-products were required
      for the two water treatment trains described in the preceding article (Miltner et
      al., 2008). To accomplish this, the finished drinking waters from each treatment
      train were sent through cation-exchange resin columns to remove hardness and free
      chlorine. Reverse osmosis membranes were then used to concentrate approximately
      2400 L of each finished water down to approximately 18 L. The resulting
      volumetric concentration factors for the chlorinated and ozonated/postchlorinated
      waters were 136- and 124-fold, respectively. The concentrates were spiked with
      select disinfection by-products (DBPs) that were lost during the concentration
      effort. The results, along with the rationale for choosing the method of
      concentration, are presented. After reintroduction of a select list of lost DBPs,
      the concentration methodology used herein was able to produce concentrates that
      retained large percentages of the DBPs that were in the initial finished drinking
      waters. Further, the distributions of the DBPs in the concentrates matched those
      found in the finished drinking waters.

PMID- 18636390
TI  - Integrated disinfection by-products mixtures research: comprehensive
      characterization of water concentrates prepared from chlorinated and
      ozonated/postchlorinated drinking water.
AB  - This article describes the disinfection by-product (DBP) characterization portion
      of a series of experiments designed for comprehensive chemical and toxicological
      evaluation of two drinking-water concentrates containing highly complex mixtures
      of DBPs. This project, called the Four Lab Study, involved the participation of
      scientists from four laboratories and centers of the U.S. Environmental
      Protection Agency (EPA) Office of Research and Development, along with
      collaborators from the water industry and academia, and addressed toxicologic
      effects of complex DBP mixtures, with an emphasis on reproductive and
      developmental effects that are associated with DBP exposures in epidemiologic
      studies. Complex mixtures of DBPs from two different disinfection schemes
      (chlorination and ozonation/postchlorination) were concentrated successfully,
      while maintaining a water matrix suitable for animal studies. An array of
      chlorinated/brominated/iodinated DBPs was created. The DBPs were relatively
      stable over the course of the animal experiments, and a significant portion of
      the halogenated DBPs formed in the drinking water was accounted for through a
      comprehensive qualitative and quantitative identification approach. DBPs
      quantified included priority DBPs that are not regulated but have been predicted
      to produce adverse health effects, as well as those currently regulated in the
      United States and those targeted during implementation of the Information
      Collection Rule. New by-products were also reported for the first time. These
      included previously undetected and unreported bromo- and chloroacids, iodinated
      compounds, bromo- and iodophenols, and bromoalkyltins.

PMID- 18636391
TI  - Integrated disinfection by-products research: salmonella mutagenicity of water
      concentrates disinfected by chlorination and ozonation/postchlorination.
AB  - Although chemical disinfection of drinking water is a highly protective public
      health practice, the disinfection process is known to produce toxic contaminants.
      Epidemiological studies associate chlorinated drinking water with quantitatively
      increased risks of rectal, kidney, and bladder cancer. One study found a
      significant exposure-response association between water mutagenicity and relative
      risk for bladder and kidney cancer. A number of studies found that several types
      of disinfection processes increase the level of mutagens detected by the
      Salmonella assay. As part of a comprehensive study to examine chlorinated and
      ozonated/postchlorinated drinking water for toxicological contaminants, the
      Salmonella mutagenicity assay was used to screen both volatile and nonvolatile
      organic components. The assay also compared the use of reverse osmosis and XAD
      resin procedures for concentrating the nonvolatile components. Companion papers
      provide the results from other toxicological assays and chemical analysis of the
      drinking water samples. The volatile components of the ozonated/postchlorinated
      and chlorinated water samples and a trihalomethane mixture were mutagenic to a
      Salmonella tester strain transfected with a rat theta-class glutathione S
      transferase and predominantly nonmutagenic in the control strain. In this study,
      the nonvolatile XAD concentrate of the untreated water possessed a low level of
      mutagenic activity. However, compared to the levels of mutagenicity in the
      finished water XAD concentrates, the contribution from the settled source water
      was minimal. The mutagenicity seen in the reverse osmosis concentrates was < 50%
      of that seen in the XAD concentrates. Overall, mutagenic responses were similar
      to those observed in other North American studies and provide evidence that the
      pilot plant produced disinfection by-products similar to that seen in other
      studies.

PMID- 18636392
TI  - Integrated disinfection by-products (DBP) mixtures research: gene expression
      alterations in primary rat hepatocyte cultures exposed to DBP mixtures formed by
      chlorination and ozonation/postchlorination.
AB  - Large-scale differential gene expression analysis was used to examine the
      biological effects of disinfected surface waters on cultured rat hepatocytes.
      Source water from East Fork Lake (Harsha Lake), a reservoir on the Little Miami
      River in Ohio, was spiked with iodide and bromide and disinfected by chlorination
      or ozonation/postchlorination. The chlorinated and ozonated/postchlorinated
      waters were concentrated, respectively, 136- and 124-fold (full strength) by
      reverse-osmosis membrane techniques. Volatile disinfection by-products (DBP) lost
      during concentration were restored to the extent possible. Primary rat
      hepatocytes were exposed to either full-strength or 1:10 or 1:20 dilutions of the
      concentrates for 24 h and assayed for cytotoxicity and gene expression
      alterations. The full-strength concentrates were cytotoxic, whereas the diluted
      samples exhibited no detectable cytotoxicity. Differential gene expression
      analysis provided evidence for the underlying causes of the severe cytotoxicity
      observed in rat hepatocytes treated with the full-strength
      ozonation/postchlorination concentrate (e.g., cell cycle arrest, metabolic
      stasis, oxidative stress). Many gene expression responses were shared among the
      hepatocyte cultures treated with dilutions of the ozonation/ postchlorination and
      chlorination concentrates. The shift in the character of the response between the
      full-strength concentrates and the diluted samples indicated a threshold for
      toxicity. A small subset of gene expression changes was identified that was
      observed in the response of hepatocytes to peroxisome proliferators, phthalate
      esters, and haloacetic acids, suggesting a peroxisome proliferative response.

PMID- 18636393
TI  - Integrated disinfection by-products mixtures research: assessment of
      developmental toxicity in Sprague-Dawley rats exposed to concentrates of water
      disinfected by chlorination and ozonation/postchlorination.
AB  - Epidemiological and animal toxicity studies have raised concerns regarding
      possible adverse health effects of disinfection by-products (DBPs) found in
      drinking water. The classes and concentrations of DBPs are influenced by the
      choice of disinfection process (e.g., chlorination, ozonation) as well as source
      water characteristics (e.g., pH, total organic carbon, bromide content).
      Disinfected waters were found to contain more than 500 compounds, many of which
      remain unidentified. Therefore, a "whole-mixture" approach was used to evaluate
      the toxic potential of alternative disinfection scenarios. An in vivo
      developmental toxicity screen was used to evaluate the adverse developmental
      effects of the complex mixtures produced by two different disinfection processes.
      Water was obtained from East Fork Lake, Ohio; spiked with iodide and bromide; and
      disinfected either by chlorination or by ozonation/postchlorination, producing
      finished drinking water suitable for human consumption. These waters were
      concentrated approximately 130-fold by reverse osmosis membrane techniques. To
      the extent possible, volatile DBPs lost in the concentration process were spiked
      back into the concentrates. These concentrates were then provided as drinking
      water to Sprague-Dawley rats on gestation days 6-16; controls received boiled,
      distilled, deionized water. The dams (19-20 per group) were allowed to deliver
      and their litters were examined on postnatal days (PD) 1 and 6. All dams
      delivered normally, with parturition occurring significantly earlier in the
      ozonation/postchlorination group. However, no effects on prenatal survival,
      postnatal survival, or pup weight were evident. Skeletal examination of the PD-6
      pups also revealed no treatment effects. Thus, approximately 130-fold higher
      concentrates of both ozonated/postchlorinated and chlorinated water appeared to
      exert no adverse developmental effects in this study.

PMID- 18636394
TI  - Integrated disinfection by-products research: assessing reproductive and
      developmental risks posed by complex disinfection by-product mixtures.
AB  - This article presents a toxicologically-based risk assessment strategy for
      identifying the individual components or fractions of a complex mixture that are
      associated with its toxicity. The strategy relies on conventional component-based
      mixtures risk approaches such as dose addition, response addition, and analyses
      of interactions. Developmental toxicity data from two drinking-water concentrates
      containing disinfection by-products (DBP) mixtures were used to illustrate the
      strategy. The results of this study showed that future studies of DBP
      concentrates using the Chernoff-Kavlock bioassay need to consider evaluating DBP
      that are concentrated more than 130-fold and using a rat strain that is more
      sensitive to chemically-induced pregnancy loss than Sprague-Dawley rats. The
      results support the planned experimental design of a multigeneration reproductive
      and developmental study of DBP concentrates. Finally, this article discusses the
      need for a systematic evaluation of DBP concentrates obtained from multiple
      source waters and treatment types. The development of such a database could be
      useful in evaluating whether a specific DBP concentrate is sufficiently similar
      to tested combinations of source waters and treatment alternatives so that health
      risks for the former may be estimated using data on the latter.

PMID- 18636395
TI  - Primary vocal cord aspergillosis caused by Aspergillus fumigatus and molecular
      identification of the isolate.
AB  - This is a case of vocal cord aspergillosis in a 36-year-old woman whose chief
      complaint was progressive hoarseness and vocal fatigue of one month duration.
      These symptoms followed the use of systemic administration of penicillin,
      cefotaxime natrium and dexamethasone to treat her rhinitis and asthma. Fiberoptic
      laryngoscopy revealed whitish plaques involving both vocal cords. Microscopic
      examination of KOH preparations and histopathology studies of tissue revealed
      dichotomously branching, hyaline, septate hyphae. Morphological and molecular
      biological identification of the fungal growth in cultures inoculated with
      clinical specimens from the patient indicated that the etiologic agent was
      Aspergillus fumigatus. The patient was cured with oral itraconazole without any
      side effects.

PMID- 18636396
TI  - [Eccrine porocarcinoma of the cheek skin with parotid gland infiltration].
AB  - BACKGROUND: Eccrine porocarcinoma is a rare malignant tumor, arising from the
      intraepithelial ductal parts of the sweat glands. Although the clinical
      appearance is variable, some tumors present with a diameter of 10 cm or more. In
      most cases the tumor presents as a slowly growing painless mass. PATIENTS AND
      METHODS: A case of a 61 year old male patient is presented, who was admitted
      because of a peripheral facial nerve palsy. The patient reported about a sting in
      this area some ten years ago with a persistent swelling. Four years ago this
      lesion began to grow slowly. RESULTS: Clinically a huge mass in the left cheek
      extended to the parotid gland was obvious. The patient underwent radical tumor
      excision with histologically clear margins. The defect was reconstructed by a
      microvascular forearmflap, the facial nerve was reconstructed using either a
      graft from the suralis nerve (for the upper part of the facial nerve) along with
      a hypoglossal facial nerve anastomosis for the lower part of the facial nerve.
      Postoperative radiation therapy was added. Histologically an eccrine
      porocarcinoma was confirmed with an infiltration of the facial nerve and the
      parotid gland. Lymph nodes in the neck were negative. DNA image cytometry
      achieved a DNA malignancy grade of 0.73, the immunohistochemical assessment using
      a monoclonal antibody against the proliferation antigen MIB-1 achieved a
      proliferation rate of < 10 %. CONCLUSIONS: Although very rare eccrine
      porocarcinoma should be considered in the differential diagnosis of slowly
      growing skin masses in the face. Therapeutically a radical resection with
      histological clear margins is recommended, in case of lymph node metastases with
      additional postoperative radiotherapy.

PMID- 18636397
TI  - Tumorous calcification causing carpal tunnel syndrome.
AB  - PURPOSE: There is little information on solitary tumorous calcification causing
      carpal tunnel syndrome in the literature. This study describes our experience
      with surgically treated cases of solitary tumorous calcification causing carpal
      tunnel syndrome. METHODS: Seven patients with symptomatic carpal tunnel syndrome
      who had tumorous calcification in the carpal tunnel confirmed by radiographical
      examinations and had then undergone open incisional carpal tunnel release were
      reviewed. The precise location and the appearance of the calcified mass were
      confirmed with the preoperative radiographic examinations and the operative
      records. The additional histology and the composition analysis of the calcified
      mass were also reviewed in five removed calcifications. RESULTS: Radiographs of
      each hand revealed a mass of calcification lying anterior to the capitate bone in
      the carpal tunnel. Intraoperatively, an oval calcified nodule, measuring 10 x 10
      x 10 - 18 mm, was observed overlying the capitate, attached firmly to the palmar
      radiocarpal extrinsic ligament. A composition with an average of 60 % basic
      calcium phosphate was revealed by infrared absorption spectrometry. Histological
      sections showed a calcified deposit surrounded by fibrocartilagenous tissue in
      three cases. CONCLUSION: These facts suggest that the pathogenesis of tumorous
      calcification causing carpal tunnel syndrome is comparable with that of
      calcifying tendinitis of the rotator cuff in which a cell-mediated reactive
      process plays an important role at the tendon insertion.

PMID- 18636398
TI  - Identifying students feigning dyslexia: preliminary findings and strategies for
      detection.
AB  - When conducting psychological evaluations, clinicians typically assume that
      individuals being evaluated are putting forth maximal effort and are not
      exaggerating or magnifying symptom complaints. Recent research, however, suggests
      that students undergoing post-secondary-level assessments to document learning
      difficulties may not always put forth their best effort, and may even be
      motivated to exaggerate or magnify symptoms. This paper presents evidence
      indicating that symptom exaggeration in this context is not only possible, but is
      indistinguishable from valid symptomatology when it occurs. We argue that symptom
      validity assessment should be included in all higher-education assessments for
      dyslexia and other specific learning disorders, and suggest some preliminary
      strategies for detection.

PMID- 18636399
TI  - In vitro evaluation of the chemoprotective action mechanisms of leontopodic acid
      against aflatoxin B1 and deoxynivalenol-induced cell damage.
AB  - Several in vitro studies showed that free radical scavengers possess
      chemopreventive properties against mycotoxin-induced cell damage which are at
      least partially associated with the induction of phase II detoxifying enzymes and
      antioxidant enzymes like glutathione S-transferase (GST) and glutathione
      peroxidase (GPx). The aim of this project was to study the chemopreventive
      effects of leontopodic acid (LA), a potent natural occurring free radical
      scavenger isolated from the aerial parts of Leontopodium alpinum. Different
      mycotoxins were evaluated in two different cell lines on the basis of their
      specific toxicity: aflatoxin B1 (AFB1) on HepG2 cells and deoxynivalenol (DON) on
      U937 cells. Cell viability and reactive oxygen species concentration were
      determined, and the effects of pre-treatment with LA on these parameters were
      investigated together with the GST and GPx activity as well as the concentration
      of reduced glutathione. The results show that LA protects U937 cells from DON
      induced cell damage but not HepG2 cells from AFB1. Moreover LA is able to enhance
      GPx activity in U937, but not GST activity in HepG2. We hypothesize that the
      increase in detoxifying enzymes is probably the main mechanism of antioxidant
      mediated chemoprevention.

PMID- 18636400
TI  - DNA damage in workers occupationally exposed to pesticide mixtures.
AB  - Pesticides are used in agriculture to protect crops but represent at the same
      time a potential risk to farmers and environment. The aim of this work is the
      evaluation of 54 subjects occupationally exposed to pesticides and 30 subjects as
      a control group using the quantification of DNA damage level by means of the
      alkaline Comet assay and the evaluation of repair processes. Damage index Comet
      assay (DICA) and damage index repair assay (DIRA) were studied in 27 pesticide
      applicator workers, 27 non-pesticide applicators and controls. Our results show
      that both exposed groups revealed significant increase in DICA when compared with
      controls (P < 0.0001), as well as in DIRA (P < 0.0001). However, the spraying
      group exhibited a marginally significant difference in DICA (P = 0.05) when years
      of exposure are considered and a significant difference (P < 0.05) when the
      personal protective equipment used by individuals was taken as a comparison
      factor. The influence of confounding factors on the genotoxic effects of
      occupational exposure to pesticides was investigated and no significant
      differences were observed considering age, gender, smoking and alcohol
      consumption in relation to DICA and DIRA. Since DNA damage is an important step
      in events leading from carcinogen exposure to cancer disease, our study
      highlights the potential health risk associated with agrochemical exposure in
      developing countries with vast cultivated areas, such as Argentina.

PMID- 18636401
TI  - Switching from the unfolded to the folded state of the helix-loop-helix domain of
      the Id proteins based on the O-acyl isopeptide method.
AB  - The inhibitors of DNA binding and cell differentiation Id1-4 are helix-loop-helix
      (HLH) proteins that negatively regulate DNA transcription by forming inactive
      dimers with ubiquitous and tissue-specific bHLH proteins, including E47 and MyoD,
      respectively. Their highly conserved HLH domains are essential for
      heterodimerization, but can also self-associate to highly stable, alpha-helix
      rich structures at low micromolar peptide concentrations. Here, we show that the
      introduction of an O-acyl isodipeptide unit involving the putative N-cap serine
      residue of the C-terminal helix completely abrogates the propensity of the Id HLH
      analogue for any secondary and tertiary structure, resulting in a random coil, as
      shown by CD measurements in nonbuffered aqueous solutions. However, the HLH fold
      reappears as soon as an O-->N intramolecular acyl migration, which occurs
      spontaneously under physiological conditions, restores the native N-cap serine
      residue. These results show that changes addressing the N-terminus of the C
      terminal helix can dramatically influence the HLH structure, and suggest that
      local interactions at the junction between the loop and the C-terminal helix
      might be crucial during the HLH folding process. Furthermore, the present study
      contributes to the evaluation of the O-acyl isodipeptide unit as a powerful tool
      to introduce a conformational switch into peptides.

PMID- 18636402
TI  - Discovery of myopodin methylation in bladder cancer.
AB  - Myopodin is an actin-binding protein that shuttles between the nucleus and the
      cytoplasm. After identifying an enriched CpG island encompassing the
      transcription site of myopodin, we aimed at evaluating the potential relevance of
      myopodin methylation in bladder cancer. The epigenetic silencing of myopodin by
      hypermethylation was tested in bladder cancer cells (n=12) before and after
      azacytidine treatment. Myopodin hypermethylation was associated with gene
      expression, being increased in vitro by this demethylating agent. The methylation
      status of myopodin promoter was then evaluated by methylation-specific polymerase
      chain reaction (MS-PCR) analyses. Myopodin was revealed to be frequently
      methylated in a large series of 466 bladder tumours (68.7%). Myopodin methylation
      was significantly associated with tumour stage (p<0.0005) and tumour grade
      (p=0.037). Myopodin expression patterns were analysed by immunohistochemistry on
      tissue arrays containing bladder tumours for which myopodin methylation was
      assessed (n=177). The presence of low nuclear myopodin expression alone (p =
      0.031) or combined with myopodin methylation (p=0.008) was associated with poor
      survival. Moreover, myopodin methylation in 164 urinary specimens distinguished
      patients with bladder cancer from controls with a sensitivity of 65.0%, a
      specificity of 79.8%, and a global accuracy of 75.3%. Thus, myopodin was
      identified to be epigenetically modified in bladder cancer. The association of
      myopodin methylation and nuclear expression patterns with cancer progression and
      clinical outcome, together with its ability to detect bladder cancer patients
      using urinary specimens, suggests the utility of incorporating myopodin
      methylation assessment in the clinical management of patients affected by
      uroepithelial neoplasias.

PMID- 18636403
TI  - Dyslexia and developmental co-ordination disorder in further and higher education
      similarities and differences. Does the 'label' influence the support given?
AB  - Developmental co-ordination disorder (DCD) is a developmental disorder affecting
      motor co-ordination. The Diagnostics Statistics Manual-IV classification for DCD
      describes difficulties across a range of activities of daily living, impacting on
      everyday skills and academic performance in school. Recent evidence has shown
      that difficulties persist into adulthood. As a consequence, increasing numbers of
      students are arriving at university and colleges in the UK with a diagnosis of
      DCD and requesting Disabled Students' Allowance (DSA) to gain support. This
      preliminary study examined a cohort of 115 students currently in further or
      higher education in order to compare and contrast similarities and differences in
      three subgroups: those with a diagnosis of DCD, a second group with DCD and
      dyslexia and a third group with dyslexia only. It examines how students were
      supported in the past and now as students. Additionally it identifies differences
      in reported strengths and difficulties. A higher percentage of those with
      dyslexia receive DSA. All students have similar types of support not dependent on
      their diagnosis. The DCD only group lives at home with parents more and has a
      significantly greater reported motor and executive functioning difficulty than
      the other two groups.

PMID- 18636404
TI  - Complexes of cationic block copolymer micelles with DNA: histone/DNA complex
      mimetics.
AB  - The formation of complexes between cationic polymeric micelles of PS-b-PQ2VP
      amphiphilic block copolymers and DNA molecules in aqueous solutions is
      investigated at pH = 7. The physicochemical characteristics of the "polyplexes"
      at different DNA/polymer ratios were characterized in terms of mass, size and
      charge using static, dynamic and electrophoretic light scattering and AFM. The
      complexes are spherical and assume their maximum size and mass around the charge
      stoichiometric ratio. After addition of increased amounts of salt in the
      solutions, partial dissociation of the systems was observed. The present systems
      can be considered as mimetics of histone/DNA complexes formed under physiological
      conditions in living cells.

PMID- 18636405
TI  - Synthesis, shape control, and optical properties of hybrid Au/Fe3O(4)
      "nanoflowers".

PMID- 18636406
TI  - Protein denaturation by combined effect of shear and air-liquid interface.
AB  - The effect of shear alone on the aggregation of recombinant human growth hormone
      (rhGH) and recombinant human deoxyribonuclease (rhDNase) has been found to be
      insignificant. This study focused on the synergetic effect of shear and gas
      liquid interface on these two model proteins. Two shearing systems, the
      concentric-cylinder shear device (CCSD) and the rotor/stator homogenizer, were
      used to generate high shear (> 10(6)) in aqueous solutions in the presence of
      air. High shear in the presence of an air-liquid interface had no major effect on
      rhDNase but caused rhGH to form noncovalent aggregates. rhGH aggregation was
      induced by the air-liquid interface and was found to increase with increasing
      protein concentration and the air-liquid interfacial area. The aggregation was
      irreversible and exhibited a first-order kinetics with respect to the protein
      concentration and air-liquid interfacial area. Shear and shear rate enhanced the
      interaction because of its continuous generation of new air-liquid interfaces. In
      the presence of a surfactant, aggregation could be delayed or prevented depending
      upon the type and the concentration of the surfactant. The effect of air-liquid
      interface on proteins at low shear was examined using a nitrogen bubbling method.
      We found that foaming is very detrimental to rhGH even though the shear involved
      is low. The use of anti-foaming materials could prevent rhGH aggregation during
      bubbling. The superior stability exhibited by rhDNase may be linked to the higher
      surface tension and lower foaming tendency of its aqueous solution. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 54: 503-512, 1997.

PMID- 18636407
TI  - Biodegradation and plant protection from the herbicide 2,4-D by plant-microbial
      associations in cotton production systems.
AB  - A significant "biosafening" protection of plants from the effect of 2,4-D in
      plant-microbial associations has been demonstrated in this study. The 2,4-D
      degrading plasmid, pJP4 was transferred into Rhizobium sp. CB1024, which
      nodulates Dolichos lablab, and Azospirillum brasilense Sp7 carrying a nifA-lacZ
      gene marker, which can colonize cotton roots. Both transconjugants degraded 2,4-D
      in pure culture via cometabolism up to 50 microg mL(-1). When the transconjugants
      were inoculated onto Dolichos lablab and cotton, respectively, such plants were
      resistant to this herbicide when the nutrient solution was treated with 2,4-D up
      to 10 microg mL(-1) for Dolichos lablab and 0.5 microg mL(-1) for cotton. Plants
      inoculated with wild-type strains were dead (Dolichos lablab) or dying (cotton).
      Because cotton is more sensitive to herbicides, only incomplete protection of
      plants was achieved with the transconjugant. Improving the effect of colonization
      of Azospirillum on cotton roots may be critical for a complete degradation and
      plant protection. The transconjugant of Rhizobium sp. CB1024 was still able to
      nodulate Dolichos lablab, N(2)-fixing activity was only slightly affected. Other
      pesticide-degrading capacities may also be inserted into those plant-associated
      bacterial strains for the degradation of these chemicals by plant-microbial
      associations. Whether such systems will be successful when applied in the field
      with competition from other bacteria is being examined. (c) 1997 John Wiley &
      Sons, Inc. Biotechnol Bioeng 53: 513-519, 1997.

PMID- 18636408
TI  - Cometabolism of chlorinated solvents by nitrifying bacteria: kinetics, substrate
      interactions, toxicity effects, and bacterial response.
AB  - Pure cultures of ammonia-oxidizing bacteria, Nitrosomonas europaea, were exposed
      to trichloroethylene (TCE), 1,1-dichloroethylene (1,1-DCE), chloroform (CF), 1,2
      dichloroethane (1,2-DCA), or carbon tetrachloride (CT), in the presence of
      ammonia, in a quasi-steady-state bioreactor. Estimates of enzyme kinetics
      constants, solvent inactivation constants, and culture recovery constants were
      obtained by simultaneously fitting three model curves to experimental data using
      nonlinear optimization techniques and an enzyme kinetics model, referred to as
      the inhibition, inactivation, and recovery (IIR) model, that accounts for
      inhibition of ammonia oxidation by the solvent, enzyme inactivation by solvent
      product toxicity, and respondent synthesis of new enzyme (recovery). Results
      showed relative enzyme affinities for ammonia monooxygenase (AMO) of 1,1-DCE
      approximately TCE > CT > NH(3) > CF > 1,2-DCA. Relative maximum specific
      substrate transformation rates were NH(3) > 1,2-DCA > CF > TCE approximately 1,1
      DCE > CT (=0). The TCE, CF, and 1,1-DCE inactivated the cells, with 1,1-DCE being
      about three times more potent than TCE or CF. Under the conditions of these
      experiments, inactivating injuries caused by TCE and 1,1-DCE appeared limited
      primarily to the AMO enzyme, but injuries caused by CF appeared to be more
      generalized. The CT was not oxidized by N. europaea while 1,2-DCA was oxidized
      quite readily and showed no inactivation effects. Recovery capabilities were
      demonstrated with all solvents except CF. A method for estimating protein yield,
      the relationship between the transformation capacity model and the IIR model, and
      a condition necessary for sustainable cometabolic treatment of inactivating
      substrates are presented. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54:
      520-534, 1997.

PMID- 18636409
TI  - Construction and performance of plug-in membrane inlet mass spectrometer for
      fermentor monitoring.
AB  - An in situ sterilizable plug-in membrane inlet mass spectrometer for monitoring
      dissolved gases and volatiles in fermentors was constructed and tested. The
      design ensured a minimal distance to be traveled by analyte molecules from the
      bulk of the fermentation broth to the ionization chamber of the mass
      spectrometer. Apart from the specific cross talk due to overlapping mass peaks
      from different compounds, we found that carbon dioxide interfered unspecifically
      with all the mass peaks of other substances, changing them by the same factor.
      The interference changed slowly with time and could be positive or negative
      depending on the history of the mass spectrometer. Also, the general sensitivity
      of the instrument changed slowly with time. These effects can be neglected or
      corrected for empirically in short-term measurements. When the fermentor was
      aerated with a three-component gas mixture including carbon dioxide, a rapid
      change in the partial pressure of carbon dioxide in the gas mixture gave rise to
      a transient in the signal of a gas whose partial pressure was kept constant. This
      effect revealed a transient change in the composition of the gas mixture in the
      bubbles caused by net import or export of carbon dioxide during equilibration
      with the new gas mixture. An experimental method to determine the effective
      partial pressures of gases in the bubbles during steady-state transport of carbon
      dioxide was designed. The plug-in membrane inlet mass spectrometer was tried as a
      probe for oxygen and ethanol in an oxystatic culture of the yeast Pichia
      stipitis. We found that it was possible to keep a steady-state concentration of
      as little as 0.5 microM throughout the lifetime of the culture. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 54: 535-542, 1997.

PMID- 18636410
TI  - A simple model describing nitrate and nitrite reduction in fluidized bed
      biological reactors.
AB  - A uniquely simple model is developed to describe the NO(3) (-) and NO(2) (-)
      concentration profiles within a dentrification fluidized bed biological reactor.
      This simple model is compared to experimental data, and to a more complex model
      similar to those previously proposed in the literature. The simple model fits the
      experimental data at least as well as the more complex model. (c) 1997 John Wiley
      & Sons, Inc. Biotechnol Bioeng 54: 543-548, 1997.

PMID- 18636411
TI  - An efficient model development strategy for bioprocesses based on neural networks
      in macroscopic balances.
AB  - In the serial gray box modeling strategy, generally available knowledge,
      represented in the macroscopic balance, is combined naturally with neural
      networks, which are powerful and convenient tools to model the inaccurately known
      terms in the macroscopic balance. This article shows, for a typical biochemical
      conversion, that in the serial gray box modeling strategy the identification data
      only have to cover the input-output space of the inaccurately known term in the
      macroscopic balances and that the accurately known terms can be used to achieve
      reliable extrapolation. The strategy is demonstrated successfully on the modeling
      of the enzymatic (repeated) batch conversion of penicillin G, for which real-time
      results are presented. Compared with a more data-driven black box strategy, the
      serial gray box strategy leads to models with reliable extrapolation properties,
      so that with the same number of identification experiments the model can be
      applied to a much wider range of different conditions. Compared to a more
      knowledge-driven white box strategy, the serial gray box model structure is only
      based on readily available or easily obtainable knowledge, so that the
      development time of serial gray box models still may be short in a situation
      where there is no detailed knowledge of the system available. (c) 1997 John Wiley
      & Sons, Inc. Biotechnol Bioeng 53: 549-566, 1997.

PMID- 18636412
TI  - Inhibition kinetics of phenol degradation from unstable steady-state data.
AB  - Multiplicity of steady states of a continuous culture with an inhibitory
      substrate was used to estimate kinetic parameters under steady-state conditions.
      A continuous culture of Pseudomonas cepacia G4, using phenol as the sole source
      of carbon and energy, was overloaded by increasing the dilution rate above the
      critical dilution rate. The culture was then stabilized in the inhibitory branch
      by a proportional controller using the carbon dioxide concentration in the
      reactor exhaust gas as the controlled variable and the dilution rate as the
      manipulated variable. By variation of the set point, several unstable steady
      states in the inhibitory branch were investigated and the specific phenol
      conversion rates calculated. In addition, phenol degradation was investigated
      under substrate limitation (chemostat operation).The results show that the phenol
      degradation by P. cepacia can be described by the same set of inhibition
      parameters under substrate limitation and under high substrate concentrations in
      the inhibitory branch. Biomass yield and maintenance coefficients were identical.
      Fitting of the data to various inhibition models resulted in the best fit for the
      Yano and Koga equation. The well-known Haldane model, which is most often used to
      describe substrate inhibition by phenol, gave the poorest fit. The described
      method allows a precise data estimation under steady-state conditions from the
      maximum of the biological reaction rate up to high substrate concentrations in
      the inhibitory branch. Inhibition parameter estimation by controlling unstable
      steady states may thus be useful in avoiding discrepancies between data generated
      by batch runs and their application to continuous cultures which have been often
      described in the literature. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng
      54: 567-576, 1997.

PMID- 18636413
TI  - Production of actinorhodin by Streptomyces coelicolor A3(2) grown in chemostat
      culture.
AB  - Streptomyces coelicolor was grown in variously limited chemostat cultures and the
      specific rate of extracellular actinorhodin production (q(actinorhodin)) was
      measured. The highest q(actinorhodin) values were observed in glucose- or ammonia
      limited cultures, whereas almost no actinorhodin was produced in sulfate-,
      phosphate-, potassium-, or magnesium-limited cultures. The effect of the dilution
      rate on actinorhodin production was studied in glucose-limited cultures. It was
      found that q(actinorhodin) was highest at D = 0.06h(-1), which was well below the
      maximal D value tested (0.14 h(-1)). This explains why, in batch cultures,
      actinorhodin production starts at the onset of the stationary phase. It was also
      found that the use of nitrilotriacetate instead of citrate as a chelating agent
      had a negative effect on actinorhodin production. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 53: 577-582, 1997.

PMID- 18636414
TI  - Gas treatment in trickle-bed biofilters: biomass, how much is enough?
AB  - The objective of this article is to define and validate a mathematical model that
      desribes the physical and biological processes occurring in a trickle-bed air
      biofilter for waste gas treatment. This model considers a two-phase system, quasi
      steady-state processes, uniform bacterial population, and one limiting substrate.
      The variation of the specific surface area with bacterial growth is included in
      the model, and its effect on the biofilter performance is analyzed. This analysis
      leads to the conclusion that excessive accumulation of biomass in the reactor has
      a negative effect on contaminant removal efficiency. To solve this problem,
      excess biomass is removed via full media fluidization and backwashing of the
      biofilter. The backwashing technique is also incorporated in the model as a
      process variable. Experimental data from the biodegradation of toluene in a pilot
      system with four packed-bed reactors are used to validate the model. Once the
      model is calibrated with the estimation of the unknown parameters of the system,
      it is used to simulate the biofilter performance for different operating
      conditions. Model predictions are found to be in agreement with experimental
      data. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 583-594, 1997.

PMID- 18636415
TI  - Antioxidant status and lipid peroxidation in the blood of breast cancer patients
      of different ages.
AB  - Oxidative stress is considered to be implicated in the pathophysiology of breast
      cancers. In this study we investigated the level of oxidative stress and
      antioxidant (AO) status in the blood of breast cancer patients of different ages.
      The level of lipid hydroperoxides (LP) was measured in blood plasma and the
      activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT),
      glutathione peroxidase (GPx), and glutathione reductase (GR) enzymes, as well as
      the level of total glutathione (GSH) and CuZnSOD protein were measured in blood
      cells of breast cancer patients and age-matched healthy subjects. Our results
      showed that breast carcinoma is related to increase of lipid peroxidation in
      plasma with concomitant decrease of AO defense capacity in blood cells, which
      becomes more pronounced during aging of the patients. Suppression of CuZnSOD
      activity related to breast cancer is most likely caused by decreased de novo
      synthesis of this enzyme. Similar patterns of suppression in CuZnSOD and CAT
      activities related to aging were recorded both in controls and patients. Age
      related decrease in CuZnSOD activity seems not to be caused by altered protein
      levels of this enzyme. Suppression of AO enzymes associated with breast cancer
      and aging is most likely the cause of increased levels of reactive oxygen species
      (ROS). Our results indicate significant role of oxidative-induced injury in the
      breast carcinogenesis, particularly during the later stages of aging. Overall,
      our data support the importance of endogenous AOs in the etiology of breast
      cancer across all levels of predicted risk.

PMID- 18636416
TI  - MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma.
AB  - Chronic pancreatitis and pancreatic adenocarcinoma are extensively studied as
      common and potentially lethal disorders. However, their causes and genetic
      background in most cases remain unclear. The C677T polymorphism in 5',10'
      methylenetetrahydrofolate reductase (MTHFR) gene may modulate the risk of
      pancreatic disorders. In this study, we tested whether MTHFR C677T polymorphism
      is associated with chronic pancreatitis and pancreatic adenocarcinoma in the
      Serbian population. DNA was extracted from blood samples of 51 chronic
      pancreatitis patients, 21 pancreatic adenocarcinoma patients, and a control group
      consisting of 50 healthy smokers. The MTHFR C677T polymorphism was analyzed by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      technique. Although, no statistically significant differences were observed in
      the distribution of MTHFR genotype or allele frequencies between patients and
      control groups, the results showed an increased frequency of homozygotes for
      MTHFR C677T polymorphism in chronic pancreatitis patients (14%) and a decreased
      frequency in pancreatic adenocarcinoma patients (5%) in comparison to the control
      group (8%). We speculate that the MTHFR C677T polymorphism could act as a
      possible risk factor for chronic pancreatitis and a possible protective factor in
      pancreatic adenocarcinoma. This observation needs further investigation in
      prospective studies on a larger number of patients, in which the effect of other
      genetic and environmental factors should also be taken into consideration.

PMID- 18636417
TI  - Neurite outgrowth of NG108-15 cells induced by heat shock protein 90 inhibitors.
AB  - We previously reported that radicicol (Rad) and geldanamycin (Geld), heat shock
      protein 90 (Hsp90) inhibitors, potentiate neurite growth of cultured sensory
      neurons from chick embryo. We now show that the antibiotics induce neurite growth
      in NG108-15 cells. Treatment of the cells with these drugs caused transient
      decrease in protein levels of Raf1, ERK1/2, phosphorylated ERK1/2, Akt1, and
      CDK4. The neurite growth of NG108-15 induced by the inhibitors was blocked by
      actynomycin D, but the neurite growth stimulated by dbcAMP in the cells was not
      affected. The neurite growth could be due to a change in the synthesis of some
      specific protein(s) and is speculated to be due to the transient downregulation
      of particular-signaling molecules stabilized by Hsp90.

PMID- 18636418
TI  - Identifying patterns of adverse event reporting for four members of the
      angiotensin II receptor blockers class of drugs: revisiting the Weber effect.
AB  - PURPOSE: To evaluate the evidence for temporal reporting patterns, such as the
      Weber effect, in spontaneous post-marketing adverse event (AE) reports submitted
      to the Food and Drug Administration (FDA), for four members of the angiotensin II
      receptor blockers drug class (ARBs). METHODS: For losartan, valsartan,
      irbesartan, and candesartan, we evaluated temporal trends in reporting for the
      total number of AE reports, serious AE reports, and direct reports from consumers
      or health care providers (direct reports) to FDA. Reporting patterns were
      considered consistent with the Weber effect when the peak occurred 2 years after
      US marketing and the number of reports declined thereafter. We tabulated the
      number of reports by year since the first report. We adjusted the total number of
      reports, number of serious AE reports, and number of direct reports by the number
      of US dispensed prescriptions. RESULTS: There were no clear temporal reporting
      patterns for the total number of reports, direct reports, or serious AE reports.
      We observed a consistent trend for the adjusted number of direct and serious AE
      reports. The adjusted number was highest in the first year and continually
      decreased over time for all four ARBs. For the adjusted total number of reports,
      the decline was not constant over time. CONCLUSION: A characteristic temporal
      pattern in the adjusted number of reports, in which the adjusted number was
      highest in the first year and declined thereafter, was identified. However, we
      did not observe a pattern consistent with the Weber effect for these four ARBs.

PMID- 18636419
TI  - Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress
      parameters in acute dichlorvos poisoning in rats.
AB  - This study examined the effects of Y-27632, a selective Rho-kinase inhibitor, on
      organophosphate-induced acute toxicity in rats. Rats were randomly divided into
      four groups as control (corn oil), dichlorvos (30 mg kg(-1) i.p.), 1 and 10 mg
      kg(-1) Y-27632 + dichlorvos groups. Cholinergic signs (fatigue, tremor, cyanosis,
      hyper-secretion, fasciculations) were observed in all the rats in the dichlorvos
      group and the mortality rate was 50%. No cholinergic findings and deaths were
      observed in the control and Y-27632 groups. Plasma cholinesterase activities were
      suppressed with dichlorvos and these reductions were attenuated with Y-27632
      pretreatment. There was a marked increase in plasma malondialdehyde level in the
      dichlorvos group, but Y-27632 pretreatment abolished this elevation. Dichlorvos
      markedly depressed cardiac paraoxonase activity, but these changes were not
      markedly modified with Y-27632. Total antioxidant capacities, total oxidant
      status, oxidative stress index, total free sulfhydryl groups and catalase
      activities in plasma and cardiac tissues were not markedly different between the
      groups. No significant changes were observed with cardiac myeloperoxidase
      activities or plasma arylesterase and ceruloplasmin activities. In conclusion,
      our results suggest that Rho-kinase pathway is involved in organophosphate
      intoxication, and a decrease in cardiac paraoxonase activities may play a role in
      the pathogenesis of acute organophosphate poisoning in rats.

PMID- 18636421
TI  - Microsynthesis and gas chromatography/electron ionization mass spectrometric and
      tandem mass spectrometric analysis of cyclic alkylphosphonates for verification
      of the Chemical Weapons Convention.
AB  - We describe the microsynthesis and gas chromatography/mass spectrometric (GC/MS)
      analysis of cyclic alkylphosphonates (CAPs), which are included in schedule 2B4
      chemicals in the Chemical Weapons Convention (CWC). The reported microsynthesis
      is efficient in comparison with traditional synthesis. GC/MS and GC/tandem mass
      spectrometric (MS/MS) analysis of a variety of CAPs revealed that their
      fragmentations were dominated by alpha-cleavages, alkene eliminations and
      hydrogen rearrangements. Based on the obtained mass spectra and precursor and
      product ion analysis of five-, six- and seven-membered cyclic alkylphosphonates,
      the proposed fragmentation routes rationalize most of the characteristic ions.

PMID- 18636420
TI  - Cognitive and mood changes in men undergoing intermittent combined androgen
      blockade for non-metastatic prostate cancer.
AB  - PURPOSE: Men with prostate-specific antigen (PSA)-only relapse of prostate cancer
      after primary therapy are generally fully functional and asymptomatic with a life
      expectancy of up to 10 or more years. Androgen deprivation therapy (ADT) is a
      common treatment option. This study examined mood and cognitive changes in
      otherwise healthy men with prostate cancer prior to, during and after ADT.
      EXPERIMENTAL DESIGN: Twenty hormone naive, eugonadal prostate cancer patients
      without evidence of metastases and with a rising PSA were treated with
      intermittent ADT consisting of 9 months of complete androgen blockade (CAB)
      achieved with combined leuprolide and flutamide followed by an 'off treatment'
      period. Cognitive function tests and mood measures were administered at baseline,
      after 3 and 9 months of ADT and after 3 months of no treatment. Twenty healthy
      control patients without prostate cancer range matched for age and education were
      tested at the same time intervals. RESULTS: ADT patients evidenced a significant
      decline in spatial reasoning, spatial abilities and working memory during
      treatment compared with baseline. No changes were noted for measures of verbal or
      spatial memory, selective attention or language. Significant changes in self
      rated mood such as increased depression, tension, anxiety, fatigue and
      irritability were evident during treatment compared with baseline for ADT
      patients. No significant changes in either cognitive tests or mood measures were
      noted for the healthy control group. CONCLUSIONS: These findings, suggest that 9
      months of combined androgen blockade may result in some adverse changes in
      cognition and mood. However, many but not all of these changes can return to
      baseline after cessation of ADT.

PMID- 18636422
TI  - Model for ion injection into a quadrupole ion trap to assess the distribution of
      initial conditions of confinement.
AB  - A pulsed ion-injection mode for a quadrupole ion trap is described. Switched
      direct current (d.c.) potentials are applied to the source and trap electrodes to
      inject the ions into the trap and slow them down. The injection time is
      sufficient to ensure a steady distribution of the injected ions at the beginning
      of the confinement. An elementary uni-dimensional model is detailed giving the
      axial positions and velocities of the ions injected into the trap. The ion
      distribution in phase space, the number of injected ions and the number of
      injected ions that will be trapped are also given. These expressions depend on
      ion position and velocity at the creation, applied potentials and spatial
      location of the source and trap electrodes. This model is validated by comparing
      simulation and experimental results. For this purpose the number of confined ions
      is plotted versus the slowing-down potentials applied on the ring and the upper
      end-cap of the trap. The size of the area of removable ions in the source is
      deduced from these results.

PMID- 18636423
TI  - Support needs and acceptability of psychological and peer consultation: attitudes
      of 108 women who had undergone or were considering prophylactic mastectomy.
AB  - OBJECTIVE: Prophylactic mastectomy (PM) offers 90% or greater reduction in risk
      of breast cancer to women at increased hereditary risk. Nonetheless, acceptance
      in North America is low (0-27%) and 25-50% of women electing surgery report
      psychological distress and/or difficulty adapting following PM. Most women also
      report reduced cancer worry postoperatively. Psychological consultation to aid
      decision-making and post-surgical coping is not routinely offered. This
      retrospective, cross-sectional study explored interest in and acceptability of
      psychological consultation for issues related to PM among 108 women who had
      undergone or were considering surgery. METHOD: Qualitative interviews were
      conducted with 26 healthy women who had undergone prophylactic mastectomy of both
      (bilateral) breasts (BPM), 45 women who had undergone prophylactic mastectomy of
      one breast (unilateral contralateral) (UPM) after diagnosis of invasive breast
      cancer in the other breast or ductal carcinoma in situ (DCIS), and 37 women who
      were considering having PM surgery. RESULTS: Of the women who had undergone PM,
      more than half felt pre-surgical psychological consultation was advisable; nearly
      2/3 thought post-surgical psychological consultation would be helpful. All women
      currently considering PM believed psychological consultation would aid decision
      making and preparation for surgery. Strong support was reported in all groups for
      the emotional and informational value of speaking with a woman who had previously
      undergone PM. CONCLUSIONS: Narratives illustrate the nature and intensity of the
      need for psychological support and describe preferences for the role of the
      psychologist. Suggestions are offered for integration of psychological services
      for women deciding about or adapting to PM.

PMID- 18636424
TI  - Mutations of the ALS gene endowing resistance to ALS-inhibiting herbicides in
      Lolium rigidum populations.
AB  - BACKGROUND: In the important grass weed Lolium rigidum (Gaud.), resistance to ALS
      inhibiting herbicides has evolved widely in Australia. The authors have
      previously characterised the biochemical basis of ALS herbicide resistance in a
      number of L. rigidum biotypes and established that resistance can be due to a
      resistant ALS and/or enhanced herbicide metabolism. The purpose of this study was
      to identify specific resistance-endowing ALS gene mutation(s) in four resistant
      populations and to develop PCR-based molecular markers. RESULTS: Six resistance
      conferring ALS mutations were identified: Pro-197-Ala, Pro-197-Arg, Pro-197-Gln,
      Pro-197-Leu, Pro-197-Ser and Trp-574-Leu. All six mutations were found in one
      population (WLR1). Each Pro-197 mutation conferred resistance to the sulfonylurea
      (SU) herbicide sulfometuron, whereas the Trp-574-Leu mutation conferred
      resistance to both sulfometuron and the imidazolinone (IMS) herbicide imazapyr. A
      derived cleaved amplified polymorphic sequences (dCAPS) marker was developed for
      detecting resistance mutations at Pro-197. Furthermore, cleaved amplified
      polymorphic sequences (CAPS) markers were developed for detecting each of the six
      mutant resistant alleles. Using these markers, the authors revealed diverse ALS
      resistant alleles and genotypes in these populations and related them directly to
      phenotypic resistance to ALS-inhibiting herbicides. CONCLUSION: This study
      established the existence of a diversity of ALS gene mutations endowing
      resistance in L. rigidum populations: 1-6 different mutations were found within
      single populations. At field herbicide rates, resistance profiles were determined
      more by the specific mutation than by whether plants were homo- or heterozygous
      for the mutation.

PMID- 18636425
TI  - Granular formulation of Fusarium oxysporum for biological control of faba bean
      and tomato Orobanche.
AB  - BACKGROUND: Orobanche spp. represent a serious threat to a wide range of crops.
      They are difficult targets for herbicides, and biological control could provide a
      possible solution. This work therefore aimed to formulate mycoherbicides of
      Fusarium with adequate shelf life and virulence against Orobanche but safe to
      faba bean and tomato. RESULTS: Only two isolates of Fusarium oxysporum Schlecht.
      (Foxy I and Foxy II) obtained from diseased Orobanche shoots were found to be
      pathogenic to Orobanche crenata Forsk. and Orobanche ramosa L. Conidial
      suspension of both isolates significantly decreased germination, attachments and
      tubercles of Orobanche. Microconidia and chlamydospores of both isolates were
      formulated as mycoherbicides encapsulated in a wheat flour-kaolin matrix (four
      different formulations). All formulations greatly diminished Orobanche emerged
      shoots, total shoot number, shoot height, attachment of emerged shoots, the
      germinated seeds that succeeded in emerging above the soil surface and dry
      weight. Meanwhile, disease incidence and disease severity of emerged shoots were
      enhanced. The shelf life was adequate, particularly for coarse, freshly prepared,
      low-temperature-stored, microconidia-rich formulations. The induced growth
      reduction of Orobanche-infected host plants seemed to be nullified by
      formulations, particularly at the highest dose. CONCLUSION: These formulations
      seemed to destroy Orobanche but appeared harmless to host plants. Hence, they
      could be efficiently used as mycoherbicides for biological control of Orobanche
      in faba bean and tomato.

PMID- 18636426
TI  - The characterization of selected drugs with infrared laser desorption/tunable
      synchrotron vacuum ultraviolet photoionization mass spectrometry.
AB  - Some selected drugs including captopril, fudosteine and racecadotril have been
      analyzed by infrared (IR) laser desorption/tunable synchrotron vacuum ultraviolet
      (VUV) photoionization mass spectrometry (PIMS). The molecular ions of captopril
      and racecadotril are exclusively observed without any fragments at near threshold
      single-photon ionization (SPI). However, fudosteine easily forms fragments even
      at a photon energy near the ionization threshold, indicating the instability of
      its molecular ion. For these drugs, a number of fragments are yielded with the
      increase of photon energy. The structures of such fragments proposed by IR LD/VUV
      PIMS are supported by electron ionization time-of-flight mass spectrometry (EI
      TOFMS) results. Fragmentation pathways are discussed in detail.

PMID- 18636427
TI  - Isotope fractionation of molecular oxygen during adsorption/desorption by
      molecular sieve zeolite.
AB  - The isotope fractionation of O(2) gas during adsorption onto, and desorption
      from, molecular sieve zeolite (MSZ) has been confirmed. It has been found that
      the magnitude of fractionation during gas adsorption for the determination of
      isotope ratio measurements by dual inlet mass spectrometry is significant during
      desorption but not during adsorption. The isotope shift will take place during
      insufficient desorption from MSZ and its magnitude varies with the amount of MSZ
      and its identity. In order to obtain complete desorption and to remove isotope
      shifts, the use of the minimum amount of 5A MSZ and additional heating at a
      temperature of 60 degrees C for a period of 10 min just before gas admission into
      the mass spectrometer are recommended.

PMID- 18636428
TI  - Gas chromatography flow rates for determining deuterium/hydrogen ratios of
      natural gas by gas chromatography/high-temperature conversion/isotope ratio mass
      spectrometry.
AB  - The effects of the gas chromatography flow rate on the determination of the
      deuterium/hydrogen (D/H) ratios of natural gas utilising gas chromatography/high
      temperature conversion/isotope ratio mass spectrometry (GC/TC/IRMS) have been
      evaluated. In general, the measured deltaD values of methane, ethane and propane
      decrease with increase in column flow rate. When the column flow rate is 1 mL/min
      or higher, which is commonly used for the determination of D/H ratios of natural
      gas, the organic H in gas compounds may not be completely converted into hydrogen
      gas. Based on the results of experiments conducted on a GC column with an i.d. of
      0.32 mm, a GC flow rate of 0.6 mL/min is proposed for determining the D/H ratios
      of natural gas by GC/TC/IRMS. Although this value may be dependent on the
      instrument conditions used in this work, we believe that correct deltaD values of
      organic compounds with a few carbon atoms are obtained only when relatively low
      GC flow rates are used for D/H analysis by GC/TC/IRMS. Moreover, as the presence
      of trace water could significantly affect the determination of D/H ratios, a
      newly designed inlet liner was used to remove trace water contained in some gas
      samples.

PMID- 18636429
TI  - A laboratory comparison of two methods used to estimate the isotopic composition
      of soil delta13CO2 efflux at steady state.
AB  - The stable isotopic composition of soil (13)CO(2) flux is important for
      monitoring soil biological and physical processes. While several methods exist to
      measure the isotopic composition of soil flux, we do not know how effective each
      method is at achieving this goal. To provide clear evidence of the accuracy of
      current measurement techniques we created a column filled with quartz sand
      through which a gas of known isotopic composition (-34.2 per thousand) and
      concentration (3,000 ppm) diffused for 7 h. We used a static chamber at
      equilibrium and a soil probe technique to test whether they could identify the
      isotopic signature of the known gas source. The static chamber is designed to
      identify the source gas isotopic composition when in equilibrium with the soil
      gas, and the soil probe method relies on a mixing model of samples withdrawn from
      three gas wells at different depths to identify the gas source. We sampled from
      ports installed along the side of the sand column to describe the isotopic and
      concentration gradient as well as to serve as a control for the soil probe. The
      soil probe produced similar isotopic and concentration values as the control
      ports, as well as Keeling intercepts. The static chamber at equilibrium did not
      identify the source gas but, when applied in a two end-member mixing model, did
      produce a similar Keeling intercept produced from the control ports. Neither of
      the methods was able to identify the source gas via the Keeling plot method
      probably because CO(2) profiles did not reach isotopic steady state. Our results
      showed that the static chamber at equilibrium should be used only with a Keeling
      plot approach and that the soil probe is able to provide estimates of uncertainty
      for the isotopic composition of soil gas as well as information pertinent to the
      soil profile.

PMID- 18636430
TI  - Infant mortality and child nutrition in Bangladesh.
AB  - The excess female infant mortality observed in South Asia has typically been
      attributed to gender discrimination in the intra-household allocation of food and
      medical care. However, studies on child nutrition find no evidence of gender
      differences. A natural explanation could be that in environments of high infant
      mortality of females, the surviving children are healthier, so that child
      nutrition cannot be studied independently of mortality. In this paper, we use
      data from the 2004 Bangladesh Demographic Health Survey to investigate if there
      are any gender differences in survival probabilities and whether this leads to
      differences in child nutrition. We argue the importance of establishing whether
      or not there exists a dependence relationship between the two random variables-
      infant mortality and child nutrition--and in order to detect this we employ a
      copula approach to model specification. The results suggest, for example, that
      while male children have a significantly lower likelihood of surviving their
      first year relative to female children, should they survive they have
      significantly better height-for-age Z-scores. From a policy perspective,
      household wealth and public health interventions such as vaccinations are found
      to be important predictors of better nutritional outcomes.

PMID- 18636431
TI  - Hydrocephalus as a possible additional contributor to cognitive outcome in
      survivors of pediatric medulloblastoma.
AB  - OBJECTIVES: The purpose of the study was to assess the relationship between
      shunted hydrocephalus and intellectual, memory and academic functioning in a
      group of survivors of pediatric medulloblastoma. METHODS: Data from measures of
      cognitive, memory, academic and visual-motor functioning were gathered
      retrospectively from 35 survivors. Of these survivors, 10 (28.6%) required
      ventriculoperitoneal-shunt placement for hydrocephalus posttumor resection.
      RESULTS: Results revealed that participants with shunted hydrocephalus
      demonstrated significantly lower IQs, lower nonverbal intellectual functioning,
      lower academic skills in writing and math, and impairments in visual-motor
      abilities when compared with those without shunt. CONCLUSIONS: These results
      highlight the need to explore other variables--in addition to radiation and
      chemotherapy--as risk factors for neurocognitive impairments in survivors.
      Furthermore, identification of physiological substrates underlying these deficits
      is needed.

PMID- 18636432
TI  - Evaluation of peripheral and autonomic neuropathy among patients with newly
      diagnosed impaired glucose tolerance.
AB  - BACKGROUND: We have aimed to investigate the presence of peripheral and autonomic
      neuropathy in individuals who had been diagnosed with impaired glucose tolerance
      (IGT) on the basis of an oral glucose tolerance test, by comparing with age
      matched healthy subjects with an oral glucose tolerance test (OGTT) in
      normoglycemic ranges. MATERIAL AND METHODS: Conventional nerve conduction
      studies, heart rate variation variability, heart rate response to deep breathing,
      heart rate response to valsalva maneuvre, blood pressure response to standing up
      quickly, hand grip test and sympathetic skin response tests were used to evaluate
      the IGT and the control subjects. RESULTS: No obvious statistical difference
      indicating peripheral neuropathy and/or cardiac autonomic neuropathy was detected
      between patient group and controls. Amplitudes of sympathetic skin response of
      two limbs (right upper and lower extremities) were lower in the IGT patient group
      when compared to healthy controls (p < 0.05) indicating the presence of sudomotor
      autonomic neuropathy. CONCLUSION: Complaints and neurological examinations of
      patients with IGT were thought to be consistent with small-fiber neuropathy in
      the early phase of glucose intolerance. Not detecting any neuropathic findings in
      conventional electroneurography should be attributed to insufficient time allowed
      for settling down of large-fiber neuropathy. Obtaining no response in some of the
      patients in addition to general decrease in the amplitudes of sympathetic skin
      responses indicates that sudomotor fibers tend to be affected earlier in
      autonomic neuropathy in the group with IGT when compared with healthy controls.
      Newly diagnosed IGT patients take receive priority in primary protection since
      the time for settling down of cardiac autonomic neuropathy was short.

PMID- 18636434
TI  - Effect of endurance training upon lipid metabolism in the liver of cachectic
      tumour-bearing rats.
AB  - The syndrome of cancer cachexia is accompanied by several alterations in lipid
      metabolism, and the liver is markedly affected. Previous studies showed that
      moderate exercise training may prevent liver fat accumulation through diminished
      delivery of lipids to the liver, increased hepatic oxidation and increased
      incorporation of triacylglycerol (TAG) into very low density lipoprotein (VLDL).
      Our aim was to examine the influence of moderate intensity training (8 weeks)
      upon TAG content, VLDL assembly and secretion, apolipoprotein B (apoB) and
      microsomal transfer protein (MTP) gene expression in the liver of cachectic
      tumour-bearing rats. Animals were randomly assigned to a sedentary control (SC),
      sedentary tumour-bearing (ST) or exercise-trained control (EC) or to an exercise
      trained tumour-bearing (ET) group. Trained rats ran on a treadmill (60% VO(2max))
      for 60 min day(-1), 5 day week(-1), for 8 weeks. TAG content and the rate of VLDL
      secretion (followed for 3 h), as well as mRNA expression of apoB and MTP, and
      total cholesterol, VLDL-TAG, VLDL-cholesterol, high density lipoprotein
      cholesterol (HDL-cholesterol) and tumour weight were evaluated. VLDL-cholesterol
      showed a decrease in ST (p < 0.05) in relation to SC. Serum TAG, VLDL-TAG and
      tissue TAG content were all increased in ST (p < 0.01), when compared with SC. ST
      showed a lower rate of VLDL secretion (p < 0.05) and reduced expression of apoB
      (p < 0.001) and MTP (p < 0.001), when compared with SC. These parameters were
      restored to control values (p < 0.05) when the animals were submitted to the
      exercise training protocol. Tumour weight decreased 10-fold after training (p <
      0.001). It is possible to affirm, therefore, that endurance training promoted the
      re-establishment of lipid metabolism in cachectic tumour-bearing animals,
      especially in relation to VLDL secretion and assembly.

PMID- 18636433
TI  - TGF-alpha induces upregulation and nuclear translocation of Hes1 in glioma cell.
AB  - Both the Notch-signaling pathway and extracellular signal regulated kinase (ERK)
      cascade are involved in a wide variety of biological processes, such as
      proliferation, differentiation, survival, and tumorigenesis. Their dysregulation
      in recent studies have been shown to be associated with glioma formation. Here,
      we show that transforming growth factor-alpha (TGF-alpha) stimulated glioma cell
      line U251 growth and can partly compensate for the inhibitory effect of Notch
      signaling inhibitor DAPT. The effect of TGF-alpha on ERK1/2 phosphorylation was
      prompt and transient and could be inhibited by mitogen-activated/extracellular
      signal-regulated kinase kinase 1/2 (MEK1/2) specific inhibitor PD98059. Moreover,
      TGF-alpha was capable of up-regulating Hairy-enhancer of split1 (Hes1) expression
      which was independent of Notch1 activation, and of introducing Hes1 nuclear
      import in the presence of ERK1/2 activation. Collectively, our data suggest a
      potential linkage between ERK activation and the Notch-signaling pathway.

PMID- 18636435
TI  - Advanced glycation end products serve as ligands for lectin-like oxidized low
      density lipoprotein receptor-1(LOX-1): biochemical and binding characterizations
      assay.
AB  - Advanced glycation end products (AGEs) are a class of complex heterogeneous
      compounds which accumulate with age and is known to be involved in the
      pathogenesis of several diseases from diabetes to atherosclerosis. AGEs serve as
      ligands for multiple receptors including scavenger receptor (SR-A), CD36, and SR
      BIota. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an
      important role in both atherosclerosis and is found to be an endothelial cell
      receptor for AGEs. To explore the binding characterization of AGEs to LOX-1, AGEs
      were prepared by three different reducing sugars (d-glucose, d-fructose, and d
      ribose) and the biochemical characterization including, free amino groups, free
      amine content, fructosamine residues, carbonyl content, fluorescence, and
      absorbance were determined. The binding activity was determined by FITC labeled
      AGEs using Chinese hamster ovary-K1 cells stably transfected with human LOX-1
      gene. The obtained AGEs showed significant differences in the extent of side
      chain modifications, carbonyl content, fluorescence, and absorption models. All
      of the AGEs showed specific and saturable binding to hLOX-1-CHO-K1 cells.
      Furthermore, dose-dependent binding processes were observed. However, the maximal
      cellular binding of AGEs differs between the sugars (glucose > ribose >
      fructose). In addition, oxidized low-density lipoprotein (ox-LDL) could
      significantly inhibit the binding of AGEs to LOX-1 with different inhibitory
      efficiency. LOX-1 serves as receptor for AGEs which may give some insight into
      the role of LOX-1 in the pathogenesis of diabetes and related disorders.

PMID- 18636436
TI  - Cognitive rehabilitation in patients with mild cognitive impairment.
AB  - OBJECTIVE: To explore the benefits of a multi-component cognitive rehabilitation
      programme in patients with mild cognitive impairment (MCI). METHODS: Patients
      with MCI (n = 18) and patients with mild dementia in Alzheimer's disease (n = 10)
      participated in a 4-week cognitive rehabilitation programme in a day clinic
      setting. The intervention was provided in group format and included activity
      planning, self-assertiveness training, relaxation techniques, stress management,
      use of external memory aids, memory training, and motor exercise. RESULTS: After
      4 weeks, MCI patients showed significant improvements on activities of daily
      living, mood, verbal and nonverbal episodic memory. In contrast, patients with
      mild dementia exhibited a non-significant increase in verbal memory but no other
      changes. MCI subjects allocated to the waiting list control condition (n = 12)
      showed a significant re-test effect on verbal episodic memory, but no improvement
      of everyday activities or mood. CONCLUSIONS: The study demonstrates that patients
      with MCI benefit from a multi-component cognitive rehabilitation programme with
      regard to activities of daily living, mood, and memory performance.

PMID- 18636438
TI  - Characterization of acetone-washed yeast biomass functional groups involved in
      lead biosorption.
AB  - The mechanism of lead cation biosorption by acetone-washed biomass of
      Saccharomyces uvarum was investigated by chemical modifications and spectroscopic
      monitoring of the cell components. Reacting the carboxyl groups with propylamine,
      which neutralizes these anions, considerably decreased the metallic ion uptake,
      indicating that negatively charged carboxyl groups play an important role in lead
      bisorption due to electrostatic attraction. After lead biosorption the
      photoacoustic Fourier transform infrared spectroscopy showed a change in the
      symmetrical stretch of the carboxylate groups of the acetone-washed yeast
      biomass, and the X-ray photoelectron spectroscopy oxygen peak was also found to
      be shifted. These findings support the hypothesis that lead uptake occurs mainly
      through binding to the carboxyl group. In X-ray photoelectron spectroscopy the
      nitrogen peak decreased after the biosorption of lead, suggesting that nitrogen
      containing groups are also involved in the biosorption process. Acylation of
      amino groups was shown to increase the lead biosorption capacity. The acylation
      reaction converts the positively charged amino group to an amide capable of
      coordination to lead cations. Deproteination by boiling the biosorbent with NaOH
      increased the lead uptake. The acetone-washed biomass uptake of lead from an
      aqueous solution at ph 5.5 was 48.9 mg/g dry weight. Pure chitin adsorbed 48.8 mg
      lead/g dry weight. Mannan isolated from S. uvarum did not adsorb lead at all.
      Electrostatic attraction of the carboxyl groups and other anions present in the
      acetone-washed biomass, and complexation with nitrogen atoms, especially in
      chitin, appear to be the main mechanisms involved in lead cation biosorption.

PMID- 18636437
TI  - Adult daughters' reports of breast cancer risk reduction and early detection
      advice received from their mothers: an exploratory study.
AB  - OBJECTIVE: Awareness of cancer family history is dependent upon communication
      between family members. Communication of this information and related decision
      making could be important factors influencing breast cancer risk reduction and
      early detection behaviors. Using survey data from 2328 women (mean age 62.5
      years) from 372 families enrolled in the Minnesota breast cancer family study, we
      explored adult daughter's reports of breast cancer risk reduction advice received
      from their mothers. METHODS AND RESULTS: Approximately 212 (9%) of respondents
      reported receiving breast cancer risk reduction advice from their mothers and 130
      (89%) reported acting upon such advice. Having a mother or first degree relative
      (FDR) with a history of breast cancer was significantly correlated with following
      advice to a higher degree as compared with those not having such family history
      (p=0.003). Most frequently reported types of advice were to have mammograms (36%)
      and to have clinical breast exams (35%). Using multivariable logistic regression
      and after accounting for non-independence of the sample, significant independent
      correlates of receiving advice included younger age, having an affected mother,
      and having a higher perceived breast cancer risk. Receiving advice was also
      correlated with engaging in a higher number of health promoting behaviors and
      ever having received a mammogram. CONCLUSIONS: Our preliminary findings are
      consistent with social influence theory and suggest that mother-daughter
      communication about reducing risk, especially among those having a FDR with
      breast cancer, could be a potential pathway through which breast cancer family
      history is associated with the adoption of breast cancer screening and risk
      reduction behaviors.

PMID- 18636439
TI  - Simultaneous measurement of glucose and glutamine in insect cell culture media by
      near infrared spectroscopy.
AB  - The purpose of this study was to develop non-invasive techniques to monitor the
      composition of cell culture media in insect cell bioreactors. Such a monitor
      could be used in conjunction with a fed-batch feeding scheme to ensure that cells
      are maintained in an optimal environment for growth and protein production.
      Glucose and glutamine concentrations in an insect cell culture bioreactor were
      determined off-line with near-infrared (NIR) absorption spectroscopy. Spectra
      were collected from 5000 to 4000 cm(-1) with a 1.5-mm optical path length.
      Partial least squares (PLS) regression was applied to correlate the collected
      spectra with the concentration of the desired analytes. Under the culture
      conditions evaluated here, glucose and glutamine concentrations ranged from 38 to
      55 mM and from 3 to 13 mM, respectively. Accurate measurements of glucose and
      glutamine in insect cell culture samples were possible over these entire ranges.
      The standard error of prediction (SEP) and mean percent error (MPE) for glutamine
      were 0.52 mM and 5.3%, respectively. Glucose could be measured with an SEP of
      1.30 mM and an MPE of 2.3%. These levels of error are quite low considering the
      changing complexity of the growth media due to the shifting levels of amino
      acids, carbohydrates, yeastolate, proteins, and cell debris. This study
      represents an important step in the development of noninvasive on-line monitoring
      devices for cell culture bioreactors.

PMID- 18636440
TI  - Mechanism of aluminum interference on uranium biosorption by Rhizopus arrhizus.
AB  - Uranium competitive uptake experiments by Rhizopus arrhizus were carried out at
      three different solution pH levels and in the presence of different
      concentrations of competing aluminum ions in order to examine the competing ion
      effect. The coion effect became more pronounced as the coion concentration in
      solution and pH level increased. A preliminary examination of the effect of
      aluminum on the rate of uranium uptake was also completed. Results showed that
      the presence of aluminum does not interfere with the kinetics of uranium uptake
      by R. arrhizus. Electron microscopic and energy dispersive X-ray analyses were
      also performed on samples of the biomass. The combination of spectral data and
      the information from the equilibrium studies and the kinetic studies suggested
      that aluminum interferes with the uranium biosorptive uptake capacity of R.
      arrhizus by the precipitation of a metastable amorphous hydroxy polymeric
      precipitate through a mechanism we refer to as steric competition.

PMID- 18636441
TI  - Production of poly(3-hydroxybutyrate) by high cell density fed-batch culture of
      Alcaligenes eutrophus with phospate limitation.
AB  - High cell density fed-batch fermentation of Alcaligenes eutrophus was carried out
      for the production of poly(3-hydroxybutyrate) (PHB) in a 60-L fermentor. During
      the fermentation, pH was controlled with NH(4)OH solution and PHB accumulation
      was induced by phosphate limitation instead of nitrogen limitation. The glucose
      feeding was controlled by monitoring dissolved oxygen (DO) concentration and
      glucose concentration in the culture broth. The glucose concentration fluctuated
      within the range of 0-20 g/L. We have investigated the effect of initial
      phosphate concentration on the PHB production when the initial volume was fixed.
      Using an initial phosphate concentration of 5.5 g/L, the fed-batch fermentation
      resulted in a final cell concentration of 281 g/L, a PHB concentration of 232
      g/L, and a PHB productivity of 3.14 g/L . h, which are the highest values ever
      reported to date. In this case, PHB content, cell yield from glucose, and PHB
      yield from glucose were 80, 0.46, and 0.38% (w/w), respectively.

PMID- 18636442
TI  - Monitoring toxicity in anaerobic digesters by the rantox biosensor: theoretical
      background.
AB  - Process control of anaerobic reactors is difficult due to the complexity of the
      methabolic pathways in the microbial consortium and to the difficulty of
      detecting and monitoring process instability in short time, before the biomass is
      poisoned by incoming toxicants. Process control based on the Rantox biosensor is
      based on the following principle: the wastewater that can potentially induce an
      overload or contains a toxicant is first tested on a small "upstream" digester
      (the Rantox). This reactor makes possible to detect the potential instability
      and, if necessary, to divert the concentrated and/or contaminated wastewater to a
      buffer tank and consequently to protect the active biomass of the full-scale
      reactor. It is generally accepted that methanogens are the most sensitive
      microorganisms in anaerobic digestion. Among these bacteria, the acetoclastic
      methanogens are of primary importance because some 70% of the converted chemical
      oxyen demand (COD) mass flow passes through acetic acid. Therefore the first
      objective in the development of the Rantox biosensor has been to monitor the
      metabolism of acetoclastic methanogens in the presence of toxicants. This article
      presents the theoretical background required to evaluate the toxicity effects by
      determining the kinetic constants of the considered microorganisms from
      experimental data. The results of two series of calibration tests, performed in
      order to obtain a preliminary evaluation of the biosensor response to overload
      and toxicity conditions, are reported. In a second article, calibration tests
      will be described which refer to two prototypes of the biosensor tested in
      different operating conditions. The crucial point related to the Rantox, i.e.,
      its comparison with a "normal" laboratory-scale digester to simulate a full-scale
      plant, will be the subject of the third (and last) article, which is planned to
      describe the development of this instrument.

PMID- 18636443
TI  - Expression of cell surface GPI-anchored human p97 in baculovirus-infected insect
      cells.
AB  - The baculovirus/insect cell system (Autographa californica multiple nuclear
      polyhedrosis virus/Spodoptera frugiperda Sf9 cells) was used to express the GPI
      anchored human melanoma tumor antigen, melanotransferrin or p97. This system
      served to study the expression and productivity of recombinant GPI-anchored p97
      by insect cells. The Sf9 cells expressed a cell surface GPI-anchored form of p97
      as well as a soluble form of p97 that did not appear to be derived from the GPI
      anchored form of p97. Both recombinant forms, although Endo H resistant, migrated
      slightly faster ( approximately 88 kDa) than the native p97 ( approximately 95-97
      kDa). The insect GPI-anchored p97 was sensitive to PI-PLC, which exposed a
      detectable cross-reacting determinant. The Sf9 cell surface p97 expression was
      similar to that of human melanoma (SK-MEL-28) cells, whereas the Sf9 cell
      specific secretion rate was 10-fold higher. Also Sf9 cells retained considerably
      higher levels of p97 within the cell. The Sf9 cell surface expression of p97
      varied with time after infection, with the maximum expression, which appeared
      independent of multiplicities of infection greater than 1, occurring at 48 h.
      After 48 h, levels of cell surface and secreted p97 fell whereas p97 retained
      within the cell increased, which possibly reflected the lytic nature of the
      expression system. The successful expression of GPI-anchored human p97 by the
      baculovirus/insect cell system not only provides a source of p97 for further
      research but also is the basis of an alternative method for the commercial
      production of GPI-anchored proteins.

PMID- 18636444
TI  - The influence of particle size distribution and operating conditions on the
      adsorption performance in fluidized beds.
AB  - The influence of matrix properties and operating conditions on the performance in
      fluidized-bed adsorption has been studied using Streamline diethyl-aminoethyl
      (DEAE), an ion exchange matrix based on quartz-weighted agarose, and bovine serum
      albumin (BSA) as a model protein. Three different particle size fractions (120
      160 microm, 120-300 microm, and 250-300 microm) were investigated. Dispersion in
      the liquid phase was reduced when particles with a wide size distribution were
      fluidized compared to narrow particle size distributions. When the mean particle
      diameter was reduced, the breakthrough capacities during frontal adsorption were
      enlarged due to a shorter diffusion path length within the matrix. At small
      particle diameters the effect of film mass transfer became more relevant to the
      adsorption performance in comparison to larger particles. Therefore matrices
      designed for fluidized-bed adsorption should have small particle diameter and
      increased mean particle density to ensure small diffusion path length in the
      particle and a high interstitial velocity to improve film mass transfer. Studies
      on the influence of sedimented matrix height on axial mixing showed an increased
      Bodenstein number with increasing bed length. Higher breakthrough capacities were
      also found for longer adsorbent beds due to reduced dispersion and improved fluid
      and particle side mass transfer. With increasing bed height the influence of flow
      rate on breakthrough capacity was reduced. For a settled bed height of 50 cm
      breakthrough capacities of 80% of the equilibrium capacity for flow rates varying
      from 3 to 9 cm/min could be achieved.

PMID- 18636445
TI  - An activity coefficient model for proteins.
AB  - Modeling of the properties of biochemical components is gaining increasing
      interest due to its potential for further application within the area of
      biochemical process development. Generally protein solution properties such as
      protein solubility are expressed through component activity coefficients which
      are studied here. The original UNIQUAC model is chosen for the representation of
      protein activity coefficients and, to the best of our knowledge, this is the
      first time it has been directly applied to protein solutions. Ten different
      protein-salt-water systems with four different proteins, serum albumin,
      alphacymotrypsin, beta-lactoglobulin and ovalbumin, are investigated. A root-mean
      squared deviation of 0.54% is obtained for the model by comparing calculated
      protein activity coefficients and protein activity coefficients deduced from
      osmotic measurements through virial expansion. Model predictions are used to
      analyze the effect of salt concentrations, pH, salt types, and temperature on
      protein activity coefficients and also on protein solubility and demonstrate
      consistency with results from other references.

PMID- 18636446
TI  - Targeted antisense modulation of inflammatory cytokine receptors.
AB  - Antisense technology is potentially a powerful means by which to selectively
      control gene expression. We have used antisense oligonucleotides to modulate the
      response of the hepatoma cell line, HepG2, to the inflammatory cytokine, IL-6, by
      inhibiting the expression of its multifunctional signal transducer, gp130. HepG2
      cells respond to IL-6 by upregulating acute phase proteins, such as haptoglobin,
      by five- to tenfold. Gp130 is central to this response, as the upregulation of
      haptoglobin is almost completely blocked by the addition of high concentrations (
      approximately 100 microg/ml) of a monoclonal antibody to gp 130. Antisense
      oligodeoxynucleotides complementary to the mRNA encoding gp 130 inhibited the
      upregulation of haptoglobin by IL-6-stimulated HepG2 cells by about 50%. However,
      a nonsense sequence also inhibited haptoglobin secretion by about 20%. To improve
      the specificity and efficiency of action, we targeted the antisense
      oligonucleotides to HepG2 cells using a conjugate of asialoglycoprotein-poly-L
      lysine. The targeted antisense reduced the binding of IL-6 to HepG2 cells,
      virtually eliminating high affinity binding. In addition, it inhibited
      haptoglobin upregulation by over 70%. Furthermore, the dose of targeted antisense
      required for biological effect was reduced by about an order of magnitude as
      compared with unconjugated antisense. These results demonstrate the potential of
      antisense oligonucleotides as a means to control the acute phase response as well
      as the need for a greater understanding of the mechanism and dynamics of
      antisense molecules as they are developed toward therapeutic application.

PMID- 18636447
TI  - Kinetics of toluene degradation by a nitrate-reducing bacterium isolated from a
      groundwater aquifer.
AB  - Groundwater from a xylene-contaminated acquifer was enriched in the laboratory in
      the presence of toluene, xylenes, ethylbenzene, and benzene. A pure culture that
      degrades toluene and m-xylene under nitrate-reducing conditions was isolated.
      Fatty acid analysis, 16S rRNA sequencing, and morphological traits indicate that
      the isolate was a strain of Azoarcus tolulyticus. The kinetics of toluene
      degradation under nitrate-reducing conditions by this isolate was determined.
      Nitrate reduction does not proceed beyond nitrite. Nitrate and toluene are
      substrate limiting at low concentrations, whereas toluene, nitrate, and nitrite
      are inhibitory at high concentrations. Several inhibition models were compared to
      experimental data to represent inhibition by these substrates. A kinetic model
      for toluene and nitrate degradation as well as for cell growth and nitrite
      production was developed and compared to experimental data. The results of this
      work may find important application in the remediation of groundwater aquifers
      contaminated with aromatic hydrocarbons.

PMID- 18636448
TI  - Protein fouling during microfiltration: comparative behavior of different model
      proteins.
AB  - Recent studies of protein fouling have provided considerable insight into both
      the underlying fouling mechanisms and the mathematical description of the flux
      decline. However, most of the data have been obtained with a single model
      protein, making it difficult to generalize the results to commercially relevant
      process streams. Experiments were thus performed using a range of proteins with
      different physicochemical characteristics to determine the relationship between
      the protein structure and fouling behavior. Fouling in these systems occurred by
      two distinct mechanisms: deposition of large protein aggregates and chemical
      attachment of native proteins to the growing deposit. The chemical attachment
      generally occurred via the formation of intermolecular disulfide linkages
      involving a free sulfhydryl group in the native protein. Proteins without a free
      sulfhydryl group were typically unable to form these intermolecular linkages. The
      quasi-steady flux for the different proteins was proportional to the square of
      the protein surface charge density, consistent with a model in which protein
      deposition occurs when the drag force on the proteins associated with the
      convective filtrate flow is sufficient to overcome electrostatic repulsive
      interactions. These results clearly demonstrate the importance of the protein
      structure, charge, and reactivity in determining the rate and extent of protein
      fouling during microfiltration.

PMID- 18636449
TI  - Bidirectional reaction steps in metabolic networks: I. Modeling and simulation of
      carbon isotope labeling experiments.
AB  - The extension of metabolite balancing with carbon labeling experiments, as
      described by Marx et al. (Biotechnol. Bioeng. 49: 11-29), results in a much more
      detailed stationary metabolic flux analysis. As opposed to basic metabolite flux
      balancing alone, this method enables both flux directions of bidirectional
      reaction steps to be quantitated. However, the mathematical treatment of carbon
      labeling systems is much more complicated, because it requires the solution of
      numerous balance equations that are bilinear with respect to fluxes and
      fractional labeling. In this study, a universal modeling framework is presented
      for describing the metabolite and carbon atom flux in a metabolic network.
      Bidirectional reaction steps are extensively treated and their impact on the
      system's labeling state is investigated. Various kinds of modeling assumptions,
      as usually made for metabolic fluxes, are expressed by linear constraint
      equations. A numerical algorithm for the solution of the resulting linear
      constrained set of nonlinear equations is developed. The numerical stability
      problems caused by large bidirectional fluxes are solved by a specially developed
      transformation method. Finally, the simulation of carbon labeling experiments is
      facilitated by a flexible software tool for network synthesis. An illustrative
      simulation study on flux identifiability from available flux and labeling
      measurements in the cyclic pentose phosphate pathway of a recombinant strain of
      Zymomonas mobilis concludes this contribution.

PMID- 18636450
TI  - Bidirectional reaction steps in metabolic networks: II. Flux estimation and
      statistical analysis.
AB  - Metabolic carbon labelling experiments enable a large amount of extracellular
      fluxes and intracellular carbon isotope enrichments to be measured. Since the
      relation between the measured quantities and the unknown intracellular metabolic
      fluxes is given by bilinear balance equations, flux determination from this data
      set requires the numerical solution of a nonlinear inverse problem. To this end,
      a general algorithm for flux estimation from metabolic carbon labelling
      experiments based on the least squares approach is developed in this contribution
      and complemented by appropriate tools for statistical analysis. The linearization
      technique usually applied for the computation of nonlinear confidence regions is
      shown to be inappropriate in the case of large exchange fluxes. For this reason a
      sophisticated compactification transformation technique for nonlinear statistical
      analysis is developed. Statistical analysis is then performed by computing
      appropriate statistical quality measures like output sensitivities, parameter
      sensitivities and the parameter covariance matrix. This allows one to determine
      the order of magnitude of exchange fluxes in most practical situations. An
      application study with a large data set from lysine-producing Corynebacterium
      glutamicum demonstrates the power and limitations of the carbon-labelling
      technique. It is shown that all intracellular fluxes in central metabolism can be
      quantitated without assumptions on intracellular energy yields. At the same time
      several exchange fluxes are determined which is invaluable information for
      metabolic engineering.

PMID- 18636451
TI  - Increasing GPI-anchored protein harvest concentrations from suspension and porous
      microcarrier CHO cell cultures.
AB  - Chinese hamster ovary (CHO) cells expressing the human melanoma tumour antigen,
      p97, were used to develop a controlled release process for the production of
      recombinant glycosyl-phosphatidylinositol (GPI) anchored proteins. The cells were
      cultured either in suspension or immobilized on porous microcarriers and p97 was
      selectively cleaved from the cell surface by the bacterial enzyme,
      phosphatidylinositol-phospholipase C (PI-PLC). The kinetics of p97 cleavage from
      the cell surface by PI-PLC was shown to be approximated by Michaelis-Menten
      kinetics. The recovered p97 concentrations were increased by reusing the PI-PLC
      enzyme solution to harvest multiple batches of cells. A convenient PI-PLC assay
      was developed to monitor the harvesting process and to determine the stability of
      PI-PLC under harvesting conditions. Although the Pl-PLC was stable under
      harvesting conditions, it rapidly adsorbed to the cell surface and was depleted
      from the reused enzyme solution. In order to maintain PI-PLC activity, it was
      necessary to add fresh PI-PLC to the reused enzyme solution before harvesting a
      fresh batch of cells. The maximum p97 concentration that could be obtained from
      harvesting CHO cells cultured on porous microcarriers was limited by the dilution
      effects of sample removal, adding fresh PI-PLC and liquid associated with settled
      microcarriers. A model was developed that adequately predicted the p97
      concentration after each harvest and the maximum p97 concentration that could be
      achieved by this harvesting method. The dilution effects were minimized by
      harvesting from centrifuged suspension culture cells and the harvested p97
      concentration was increased by over sixfold to 0.64 mg/mL.

PMID- 18636452
TI  - Application of numerical modeling for the development of optimized complex medium
      for D-hydantoinase production from Agrobacterium radiobacter NRRL B 11291.
AB  - D-Hydantoinases (E.C.3.5.2.2) are commercially valuable enzymes involved in the
      production of D-amino acids. However, commercial exploitation of the biological
      process is rare, mainly because sufficient details are not available on the
      efficient production of these enzymes by microorganisms. In the present study,
      Agrobacterium radiobacter was used as the source of D-hydantoinase and its
      production was optimized with inexpensive carbon and nitrogen sources. The four
      media components selected to study their effect on biomass and/or enzyme
      activities were molasses, ammonium nitrate, sodium di-hydrogen orthophosphate,
      and manganese chloride. With the use of an empirical modeling technique (response
      surface method), we have optimized both biomass and enzyme production in this
      organism, with a minimal number of batches. Experiments were performed with
      optimized media components to validate the model. The maximum level of enzyme and
      biomass obtained was 35 U/mL and 1.69 mg/mL, respectively.

PMID- 18636453
TI  - Biodegradation of phenol at high initial concentrations in two-phase partitioning
      batch and fed-batch bioreactors.
AB  - A two-phase organic-aqueous system was used to degrade phenol in both batch and
      fed-batch culture. The solvent, which contained the phenol and partitioned it
      into the aqueous phase, was systematically selected based on volatility,
      solubility in the aqueous phase, partition coefficient for phenol,
      biocompatibility, and cost. The two-phase partitioning bioreactor used 500 mL of
      2-undecanone loaded with high concentrations of phenol to deliver the xenobiotic
      to Pseudomonas putida ATCC 11172 in the 1-L aqueous phase, at subinhibitory
      levels. The initial concentrations of phenol selected for the aqueous phase were
      predicted using the experimentally determined partition coefficient for this
      ternary system of 47.6. This system was initially observed to degrade 4 g of
      phenol in just over 48 h in batch culture. Further loading of the organic phase
      in subsequent experiments demonstrated that the system was capable of degrading
      10 g of phenol to completion in approximately 72 h. The higher levels of phenol
      in the system caused a modest increase in the duration of the lag phase, but did
      not lead to complete inhibition or cell death. The use of a fed-batch approach
      allowed the system to ultimately consume 28 g of phenol in approximately 165 h,
      without experiencing substrate toxicity. In this system, phenol delivery to the
      aqueous phase is demand based, and is directly related to the metabolic activity
      of the cells. This system permits high loading of phenol without the
      corresponding substrate inhibition commonly seen in conventional bioreactors.

PMID- 18636454
TI  - Biodegradation of paint stripper solvents in a modified gas lift loop bioreactor.
AB  - Paint stripping wastes generated during the decontamination and decommissioning
      of former nuclear facilities contain paint stripping organics (dichloromethane, 2
      propanol, and methanol) and bulk materials containing paint pigments. It is
      desirable to degrade the organic residues as part of an integrated chemical
      biological treatment system. We have developed a modified gas lift loop
      bioreactor employing a defined consortium of Rhodococcus rhodochrous strain OFS
      and Hyphomicrobium sp. DM-2 that degrades paint stripper organics. Mass transfer
      coefficients and kinetic constants for biodegradation in the system were
      determined. It was found that transfer of organic substrates from surrogate waste
      into the air and further into the liquid medium in the bioreactor were rapid
      processes, occurring within minutes. Monod kinetics was employed to model the
      biodegradation of paint stripping organics. Analysis of the bioreactor process
      was accomplished with BIOLAB, a mathematical code that simulates coupled mass
      transfer and biodegradation processes. This code was used to fit experimental
      data to Monod kinetics and to determine kinetic parameters. The BIOLAB code was
      also employed to compare activities in the bioreactor of individual microbial
      cultures to the activities of combined cultures in the bioreactor. This code is
      of benefit for further optimization and scale-up of the bioreactor for treatment
      of paint stripping and other volatile organic wastes in bulk materials.

PMID- 18636455
TI  - An on-line physiological state recognition system for the lysine fermentation
      process based on a metabolic reaction model.
AB  - A metabolic reaction model was developed for the lysine fermentation process by
      Corynebacterium glutamicum AJ-3462 to estimate the physiological state of the
      cells-that is, the growth and production activity, and the flux distribution of
      metabolites-from on-line measurable rates only. First, the extended Kalman filter
      was applied to eliminate noise in the measured rates. Then, using the metabolic
      reaction model, the lysine production rate and flux distribution were calculated.
      The estimation results allowed the physiological state of lysine production to be
      recognized, and an appropriate measure corresponding to the estimated state, such
      as intermittent addition of glucose and/or leucine, to be taken to maintain a
      high level of lysine productivity in batch culture. Finally, application of the
      recognition system enabled lysine to be produced from glucose at a higher yield
      than that from glucose- or leucine-limited exponential fed-batch cultures.

PMID- 18636456
TI  - Reductive dechlorination of PCB-contaminated raisin river sediments by anaerobic
      microbial granules.
AB  - A polychlorinated biphenyl (PCB)-dechlorinating anaerobic microbial consortium,
      developed in a granular form, demonstrated extensive dechlorination of PCBs
      present in Raisin River sediments at room (20 degrees to 22 degrees C) and at a
      relatively low (12 degrees C) temperature. Highly chlorinated PCB congeners were
      dechlorinated and less chlorinated compounds were produced. The homolog
      comparison showed that tri-, tetra-, penta-, hexa-, and heptachlorobiphenyl
      compounds decreased significantly, and mono- and dichlorobiphenyl compounds
      increased. After 32 weeks of incubation at 12 degrees C, the predominant less
      chlorinated products included 2-, 4-, 2-2/26-, 24-, 2-4-, 24-2-, 26-2-, and 26-4
      CB. Among these, 24- and 24-2-CB did not accumulate at room temperature,
      suggesting a further dechlorination of these congeners. Predominantly meta
      dechlorination (i.e., pattern M) was catalyzed by the microbial consortium in the
      granules. Dechlorination in the control studies without granules was not
      extensive. This study is the first demonstration of enhanced reductive
      dechlorination of sediment PCBs by an exogenous anaerobic microbial consortium.

PMID- 18636457
TI  - Modeling microbial chemotaxis in a diffusion gradient chamber.
AB  - The diffusion gradient chamber (DGC) has proven to be a useful experimental tool
      for studying population-level microbial growth and chemotaxis. A mathematical
      model capable of reproducing the population-level patterns formed as a result of
      cellular growth and chemotaxis in the DGC has been developed. The model consists
      of coupled partial differential balance equations for cells, chemoattractants,
      and a nutrient, which are solved simultaneously by the alternating direction
      implicit method. Modeling simulation results were compared with population-level
      migration patterns of Escherichia coli growing on glycerol and responding to a
      gradient of the chemoattractant aspartate for two different initial conditions.
      To accurately reproduce the experimental results, a second chemoattractant
      equation was necessary. The second chemoattractant has been identified as oxygen
      by directly measuring oxygen gradients in the DGC. Important trends observed
      experimentally and reproduced by the model include the formation of a chemotactic
      wave, a reduction in the wave velocity as it encounters higher chemoattractant
      concentrations, and chemotaxis in response to two different chemoattractants
      simultaneously. The model was also used to study the relative magnitude of cell
      fluxes due to random motility and chemotaxis, and the suppression of chemotaxis
      due to receptor saturation.

PMID- 18636458
TI  - Abrasion of suspended biofilm pellets in airlift reactors: effect of particle
      size.
AB  - The detachment of biomass from suspended biofilm pellets in three-phase internal
      loop airlift reactors was investigated under non-growth conditions, and in the
      presence of bare carrier particles. In the experiments the size of biofilm
      pellets and bare carrier particles was varied. Results show that an increase in
      particle size drastically increases the abrasion rate caused by particle
      collisions. This increase is larger than predicted by conventional collision
      theory, which accounts for changes in collision frequency and collision impact.
      However, collision theory was formulated for neutrally buoyant particles which
      follow the liquid flow. This condition does not hold for biofilm pellets and
      carrier particles. The difference might therefore be caused by differences in
      particle responses to flow fluctuations. An empirical relationship, including
      this flow response, was formulated. The collision impact is also strongly
      affected by the roughness of a bare carrier particle: sharp and edgy particles
      cause much more damage than smoother ones.

PMID- 18636459
TI  - Recombinant microorganisms for industrial production of antibiotics.
AB  - The enhancement of industrial antibiotic yield has been achieved through
      technological innovations and traditional strain improvement programs based on
      random mutation and screening. The development of recombinant DNA techniques and
      their application to antibiotic producing microorganisms has allowed yield
      increments and the design of biosynthetic pathways giving rise to new
      antibiotics. Genetic manipulations of the cephalosporin producing fungus
      Cephalosporium acremonium have included yield improvements, accomplished
      increasing biosynthetic gene dosage or enhancing oxygen uptake, and new
      biosynthetic capacities as 7-aminocephalosporanic acid (7-ACA) or penicillin G
      production. Similarly, in Penicillium chrysogenum, the industrial penicillin
      producing fungus, heterologous expression of cephalosporin biosynthetic genes has
      led to the biosynthesis of adipyl-7-aminodeacetoxycephalosporanic acid (adipyl-7
      ADCA) and adipyl-7-ACA, compounds that can be transformed into the economically
      relevant 7-ADCA and 7-ACA intermediates. Escherichia coli expression of the genes
      encoding D-amino acid oxidase and cephalosporin acylase activities has simplified
      the bioconversion of cephalosporin C into 7-ACA, eliminating the use of organic
      solvents. The genetic manipulation of antibiotic producing actinomycetes has
      allowed productivity increments and the development of new hybrid antibiotics. A
      legal framework has been developed for the confined manipulation of genetically
      modified organisms.

PMID- 18636460
TI  - Biocatalytic polyester synthesis: analysis of the evolution of molecular weight
      and end group functionality.
AB  - The enzymatic synthesis of polyesters from activated diesters and diols has been
      investigated. Differences between enzymatic synthesis and traditional chemical
      condensation processes are discussed. The disappearance of monomers during the
      initial phase of reaction indicates that enzyme has a higher specificity for
      transesterification of ester-terminated oligomers. During the intermediate phase,
      enzymatic polymerization involves a competition between diol and enzyme-bound
      water for the nucleophilic attack of the acyl enzyme intermediate. Competition
      between enzymatic transesterification and hydrolysis at different stages of
      polymerization in nonaqueous media is responsible for termination of polyesters
      with acid end-groups and also for limiting the polymer molecular weight. The
      resulting oligoester consists of chains that are either terminated with - OH
      groups and/or - COOH groups. We have used Matrix Assisted Laser
      Desorption/Ionization - Time of Flight Mass spectroscopy (MALDI-TOF) along with
      colorimetric titration techniques to determine the acidity of enzyme-synthesized
      polyesters. This paper addresses how the enzymatic polymerization proceeds, and
      compares our results to the growing literature in this field.

PMID- 18636461
TI  - Adipose-derived stem cell: a better stem cell than BMSC.
AB  - To further study the proliferation and multi-differentiation potentials of
      adipose-derived stem cells (ADSCs), the cells were isolated with improved methods
      and their growth curves were achieved with cck-8. Surface protein expression was
      analyzed by flow cytometry to characterize the cell phenotype. The multi-lineage
      potential of ADSCs was testified by differentiating cells with adipogenic,
      chondrogenic, osteogenic, and myogenic inducers. The results showed that about 5
      x 10(5) stem cells could be obtained from 400 to 600 mg adipose tissue. The ADSCs
      can be continuously cultured in vitro for up to 1 month without passage and they
      have several logarithmic growth phases during the culture period. Also, the flow
      cytometry analysis showed that ADSCs expressed high levels of stem cell-related
      antigens (CD13, CD29, CD44, CD105, and CD166), while did not express
      hematopoiesis-related antigens CD34 and CD45, and human leukocyte antigen HLA-DR
      was also negative. Moreover, stem cell-related transcription factors, Nanog, Oct
      4, Sox-2, and Rex-1 were positively expressed in ADSCs. The expression of
      alkaline phosphatase (ALP) was detected in the early osteogenic induction and the
      calcified nodules were observed by von Kossa staining. Intracellular lipid
      droplets could be observed by Oil Red staining. Differentiated cardiomyocytes
      were observed by connexin43 fluorescent staining. In order to obtain more stem
      cells, we can subculture ADSCs every 14 days instead of the normal 5 days. ADSCs
      still keep strong proliferation ability, maintain their phenotypes, and have
      stronger multi-differentiation potential after 25 passages.

PMID- 18636462
TI  - Developing anticancer chemotherapy services in a developing country: Hodgkin
      lymphoma experience.
AB  - BACKGROUND AND OBJECTIVE: Reporting on how the cancer treatment facilities were
      developed at a medical college hospital in India and the profile and outcome of
      patients with Hodgkin lymphoma (HL) at this new center were the objectives of the
      study. METHODS: Patients under 18 years with a diagnosis of HL were evaluated
      using abdominal ultrasonography, CT scan examination of chest, abdomen and pelvis
      and bone marrow examination. Most patients were treated with combination
      chemotherapy. Departments of Radiodiagnosis and Pathology were involved for
      evaluation. Radiotherapy when required was made available at a nearby hospital.
      RESULTS: Thirty-five patients between 1.2 and 18 years (median age 7 years) were
      diagnosed as HL during the study period. Advanced disease (Stage IIb or more) was
      present in 83% cases. Mixed cellularity was the commonest histological subtype
      (50.5%). Primary therapy used was COPP in 29 (83%) cases. Of the 34 patients who
      received treatment 30 showed initial good response to therapy. One patient
      responded to ABVD after having progression on COPP. Of 31 responders, 4 relapsed.
      Twenty-seven patients (80%) are surviving free of disease for a median follow up
      of 4.5 years (range 1.5-18 years). Chemotherapy was well tolerated. Febrile
      neutropenia occurred in four cases. CONCLUSIONS: Pediatric HL in India was
      characterized by advanced disease at presentation. Mixed-cellularity was the
      predominant histological subtype. An effective program was developed with initial
      attention to patients with HL.

PMID- 18636463
TI  - Nutritional status at diagnosis of children with malignancies in Casablanca.
AB  - INTRODUCTION: Nutritional assessment is an essential component of the initial
      assessment of children with cancer. Malnutrition may be present at diagnosis due
      to the effects of the malignancy or, in low income countries (LIC), due to
      poverty and an inadequate diet. PURPOSE: The aim of this study is to evaluate the
      prevalence of malnutrition at diagnosis in children with cancer in Morocco.
      PROCEDURE: Nutritional status of 100 children aged less than 18 years with newly
      diagnosed malignancy between January 2005 and January 2006 was evaluated by
      anthropometric and biochemical parameters before initiating therapy. We measured
      weight, height, weight-for-height using z-scores index for children and body mass
      index for adolescents, triceps skinfold thickness and mid-upper arm
      circumference, and serum albumin. RESULTS: A total of 100 patients were included.
      The mean age was 7 years (range 1 to 18 years). Sixty percent were boys. The
      diagnosis was: Burkitt lymphoma (n = 19), acute myeloblastic leukaemia (n = 18),
      acute lymphoblastic leukaemia (n = 14), rhabdomyosarcoma (n = 13), Ewing sarcoma
      (n = 7), nephroblastoma (n = 6), Hodgkin disease (n = 5), osteosarcoma (n = 5),
      retinoblastoma (n = 4), neuroblastoma (n = 3), germ cell tumor (n = 3), orbital
      lymphoma (n = 1), cerebral lymphoma (n = 1), ependymoma (n = 1). Incidence of
      malnutrition ranged from 20 to 50%, depending upon the measurement used.
      CONCLUSION: The prevalence of malnutrition in this study was high, so
      interventions are being implemented to improve the nutritional status of these
      patients.

PMID- 18636464
TI  - Three single nucleotide polymorphisms leading to non-synonymous amino acid
      substitution in the human ribonuclease 2 and angiogenin genes exhibit markedly
      less genetic heterogeneity in six populations.
AB  - Angiogenin and ribonuclease 2 (RNase 2) are members of the human RNase
      superfamily. Although three potential single nucleotide polymorphisms (SNPs) in
      these genes, which could give rise to an amino acid substitution in the protein,
      have been identified, relevant population data are not available, and accordingly
      they have not been applied to clinical-genetic analysis. For this purpose, a
      novel genotyping method for each SNP using the mismatched PCR-restriction
      fragment length polymorphism technique has been developed. Using this method, the
      genotype distribution of each SNP was investigated in six populations: Japanese
      (n = 167), Korean (n = 90), Mongolian (n = 92), Ovambos (n = 86), Turkish (n =
      87), and German (n = 70). In all the populations, only one genotype was found in
      each SNP. Irrespective of differences in ethnic groups, the angiogenin and RNase
      2 genes appear to exhibit markedly less genetic heterogeneity with regard to
      these SNPs.

PMID- 18636465
TI  - iHEA student competition "Young Researchers In Health Economics".

PMID- 18636466
TI  - Sieve-based device for MALDI sample preparation. I. Influence of sample
      deposition conditions in oligonucleotide analysis to achieve significant
      increases in both sensitivity and resolution.
AB  - Spraying of oligonucleotide-matrix solutions through a stainless steel (ss) sieve
      (38 microm, 450 mesh) leads to the formation, on the matrix-assisted laser
      desorption/ionization (MALDI) sample holder, of uniformly distributed
      microcrystals, well separated from each other. When the resulting sample holder
      surface is irradiated by laser, abundant molecular species form, with a clear
      increase in both intensity and resolution with respect to values obtained by
      'Dried Droplet', 'Double Layer', and 'Sandwich' deposition methods. In addition,
      unlike the usual situation, the sample is perfectly homogeneous, and identical
      spectra are obtained by irradiating different areas. On one hand, the data
      indicate that this method is highly effective for oligonucleotide MALDI analysis,
      and on the other, that it can be validly employed for fully automated MALDI
      procedures.

PMID- 18636467
TI  - Experimental measurements and theoretical calculations of the chemical shifts and
      coupling constants of three azines (benzalazine, acetophenoneazine and
      cinnamaldazine).
AB  - Three azines, two of them doubly labeled with (15)N, have been studied by
      multinuclear magnetic resonance in solution and in the solid state. The spectral
      parameters obtained by iterative analyses have been compared with DFT/B3LYP
      calculated values (absolute shieldings and coupling constants). The agreement is
      generally good. Some anomalies have been discussed in relation to the structure
      of these compounds.

PMID- 18636468
TI  - Z,E-isomerization mechanism for N-arylthio-1,4-benzoquinonimines: DNMR and DFT
      investigations.
AB  - Z,E-isomerization has been investigated for the series of the N-arylthio-1,4
      benzoquinonimines using a line shape analysis in the (1)H NMR spectra.
      Thermodynamic parameters and substituent effects have been analyzed for the
      isomerization process. It has been shown based on the DFT (B3LYP) calculations
      that the dynamic transformation for N-arylthio-1,4-benzoquinonimines should be
      considered as a combination of the two different processes, a rotation about the
      N-S bond and an inversion at nitrogen via the transition state with the linear
      C=N-S moiety. The free energies of activation for the isomerization (DeltaG(298
      K)) measured experimentally depend on the substitution in the quinonimine moiety
      and phenyl ring and can be referred either to the inversion of the nitrogen atom
      or to the hindered rotation about the N-S bond.

PMID- 18636469
TI  - Photoionization studies on various quinones by an infrared laser
      desorption/tunable VUV photoionization TOF mass spectrometry.
AB  - Photoionization and dissociative photoionization characters of six quinones,
      including 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), 9,10
      phenanthroquinone (PQ), 9,10-anthraquinone (AQ), benz[a]- anthracene-7,12-dione
      (BAD) and 1,2-acenaphthylenedione (AND) have been studied with an infrared laser
      desorption/tunable synchrotron vacuum ultraviolet (VUV) photoionization mass
      spectrometry (IR LD/VUV PIMS) technique. Mass spectra of these compounds are
      obtained at different VUV photon energies. Consecutive losses of two carbon
      monoxide (CO) groups are found to be the main fragmentation pathways for all the
      quinones. Detailed dissociation processes are discussed with the help of ab
      initio B3LYP calculations. Ionization energies (IEs) of these quinones and
      appearance energies (AEs) of major fragments are obtained by measuring the
      photoionization efficiency (PIE) spectra. The experimental results are in good
      agreement with the theoretical data.

PMID- 18636470
TI  - Expanding the understanding of the treatment of chronic angina: a 21st century
      approach-part II.
AB  - Three randomized, clinical trials of the drug ranolazine relate to patients with
      symptomatic myocardial ischemia. A fourth randomized, controlled, clinical trial
      compares optimal medical therapy with percutaneous coronary intervention (PCI)
      plus medical therapy.

PMID- 18636471
TI  - The evolution of brachiation in ateline primates, ancestral character states and
      history.
AB  - This study examines how brachiation locomotion evolved in ateline primates using
      recently-developed molecular phylogenies and character reconstruction algorithms,
      and a newly-collected dataset including the fossils Protopithecus, Caipora, and
      Cebupithecia. Fossils are added to two platyrrhine molecular phylogenies to
      create several phylogenetic scenarios. A generalized least squares algorithm
      reconstructs ateline and atelin ancestral character states for 17 characters that
      differentiate between ateline brachiators and nonbrachiators. Histories of these
      characters are mapped out on these phylogenies, producing two scenarios of
      ateline brachiation evolution that have four commonalities: First, many
      characters change towards the Ateles condition on the ateline stem lineage before
      Alouatta splits off from the atelins, suggesting that an ateline energy
      maximizing strategy began before the atelines diversified. Second, the ateline
      last common ancestor is always reconstructed as an agile quadruped, usually with
      suspensory abilities. It is never exactly like Alouatta and many characters
      reverse and change towards the Alouatta condition after Alouatta separates from
      the atelins. Third, most characters undergo homoplastic change in all ateline
      lineages, especially on the Ateles and Brachyteles terminal branches. Fourth,
      ateline character evolution probably went through a hindlimb suspension with tail
      bracing phase. The atelines most likely diversified via a quick adaptive
      radiation, with bursts of punctuated change occurring in their postcranial
      skeletons, due to changing climatic conditions, which may have caused competition
      among the atelines and between atelines and pitheciines.

PMID- 18636472
TI  - FATT-CTL assay for detection of antigen-specific cell-mediated cytotoxicity.
AB  - Here we describe a flowcytometric assay that measures the defining function of
      virus-specific cytotoxic T lymphocytes (CTL), i.e., killing viral protein
      expressing cells. The fluorescent antigen-transfected target cell (FATT)-CTL
      assay requires no viruses, recombinant viral vectors, or radioactive isotopes to
      generate CTL target cells that present naturally processed epitopes. It
      facilitates developing standardized applications in clinical trial settings.
      Plasmid vectors encoding antigen-green fluorescent protein (GFP) fusion proteins
      were used directly to nucleofect immortalized B cells or peripheral blood
      mononuclear cells (PBMCs). Elimination of antigen-GFP expressing cells by cloned
      CTL, in vitro sensitized PBMC, or ex vivo PBMC was quantified following a 4-18-h
      coculture period by flowcytometry. This technology successfully detected cell
      mediated cytotoxicity in studies involving human PBMC and various viral antigens,
      including structural proteins of influenza A virus, and structural and
      nonstructural HIV proteins. Standardized protocols are currently being developed
      in the framework of a clinical immunotherapy trial in HIV-infected individuals.
      The FATT-CTL assay principles facilitate standardized flowcytometric detection of
      antigenic protein-specific cell-mediated cytotoxicity in many different basic
      research and clinical trial settings. By measuring their defining function, the
      FATT-CTL assay contributes to a more complete assessment of antigen-specific CTL
      responses to infection and vaccination.

PMID- 18636473
TI  - Comparing flow cytometry and fluorescence microscopy for analyzing human sperm
      DNA fragmentation by TUNEL labeling.
AB  - Conflicting results are reported by recent studies comparing flow cytometry (FCM)
      and fluorescence microscopy (FM) for detecting sperm DNA fragmentation by TUNEL
      assay. Each of the two technologies has specific peculiarities and limitations,
      but whereas the limitations of FM observation are well known, the biases due to
      the inability of FCM to recognize morphologically analyzed cells are less
      explored. In particular, so far, FCM analysis of sperm DNA fragmentation have
      included in the analyses M540 bodies, round semen structures exhibiting FSC/SSC
      properties similar to sperm. Semen M540 bodies, altogether with the occurrence of
      two sperm populations with different nuclear staining, concur to an
      underestimation of values of sperm DNA fragmentation by FCM. However, even
      considering such bias, the observed discrepancies between the performance of FM
      and FCM are not fully explained. We discuss here the possible variables that may
      affect the results of each of the two technologies and the necessary efforts to
      be taken to address this issue.

PMID- 18636474
TI  - Permeation of water through the KcsA K+ channel.
AB  - Previous studies have reported that the KcsA potassium channel has an osmotic
      permeability coefficient of 4.8 x 10(-12) cm3/s, giving it a significantly higher
      osmotic permeability coefficient than that of some membrane channels specialized
      in water transport. This high osmotic permeability is proposed to occur when the
      channel is depleted of potassium ions, the presence of which slow down the water
      permeation process. The atomic structure of the potassium-depleted KcsA channel
      and the mechanisms of water permeation have not been well characterized so far.
      Here, all-atom molecular dynamics simulations, in conjunction with an umbrella
      sampling strategy and a nonequilibrium approach to simulate pressure gradients
      are employed to illustrate the permeation of water in the absence of ions through
      the KcsA K+ channel. Equilibrium molecular dynamics simulations (95 ns combined
      total length) identified a possible structure of the potassium-depleted KcsA
      channel, and umbrella sampling calculations (160 ns combined total length)
      revealed that this structure is not permeable by water molecules moving along the
      channel axis. The simulation of a pressure gradient across the channel (30 ns
      combined total length) identified an alternative permeation pathway with a
      computed osmotic permeability of approximately (2.7 +/- 0.9) x 10(-13) cm3/s.
      Water fluxes along this pathway did not proceed through collective water motions
      or transitions to vapor state. All of the major results of this study were robust
      against variations in a wide set of simulation parameters (force field, water
      model, membrane model, and channel conformation).

PMID- 18636475
TI  - Measurement of left ventricular mass by contrast ventriculography.
AB  - BACKGROUND: Elevated left ventricular mass (LVM) has been shown to be an
      important predictor of adverse cardiac events. Calculation of LVM using contrast
      ventriculography, as described by Rackley, involves measuring left ventricular
      wall thickness in a single plane, with assumptions made about ventricular
      geometry. HYPOTHESIS: We hypothesized that a modification of the Rackley method,
      involving multiple measurements of left ventricular (LV) wall thickness in 2
      orthogonal planes, may add value in the determination of LVM in patients with LV
      remodeling and dysfunction. METHODS: The LVM was determined in 24 patients with
      LV dysfunction who had undergone both cardiac magnetic resonance imaging (CMRI)
      and contrast left ventriculography. Right anterior oblique (RAO) and left
      anterior oblique (LAO) still frames in diastole were used to measure LV length,
      chamber area, and wall thickness. From these variables, LV volume, myocardial
      volume, and LVM were calculated. The LVM calculations using an average wall
      thickness from the LAO and RAO projections were compared with LVM measured by
      CMRI. RESULTS: Eighty eight percent of patients had hypertension, 100% had
      coronary artery disease, and mean left ventricular ejection fraction by contrast
      left ventriculography was 41 +/- 14%. Averaging left ventricular wall thickness
      from RAO and LAO projections using biplane ventriculography for LVM calculation
      yielded a strong correlation (r = 0.77, p < 0.01) with LVM calculated from CMR.
      CONCLUSIONS: In patients with left ventricular dysfunction, biplane left
      ventricular wall thickness measurements for contrast ventriculography LVM
      calculations render a strong correlation with LVM calculated by CMRI.

PMID- 18636476
TI  - Genome-wide enzyme annotation with precision control: catalytic families (CatFam)
      databases.
AB  - In this article, we present a new method termed CatFam (Catalytic Families) to
      automatically infer the functions of catalytic proteins, which account for 20-40%
      of all proteins in living organisms and play a critical role in a variety of
      biological processes. CatFam is a sequence-based method that generates sequence
      profiles to represent and infer protein catalytic functions. CatFam generates
      profiles through a stepwise procedure that carefully controls profile quality and
      employs nonenzymes as negative samples to establish profile-specific thresholds
      associated with a predefined nominal false-positive rate (FPR) of predictions.
      The adjustable FPR allows for fine precision control of each profile and enables
      the generation of profile databases that meet different needs: function
      annotation with high precision and hypothesis generation with moderate precision
      but better recall. Multiple tests of CatFam databases (generated with distinct
      nominal FPRs) against enzyme and nonenzyme datasets show that the method's
      predictions have consistently high precision and recall. For example, a 1% FPR
      database predicts protein catalytic functions for a dataset of enzymes and
      nonenzymes with 98.6% precision and 95.0% recall. Comparisons of CatFam databases
      against other established profile-based methods for the functional annotation of
      13 bacterial genomes indicate that CatFam consistently achieves higher precision
      and (in most cases) higher recall, and that (on average) CatFam provides 21.9%
      additional catalytic functions not inferred by the other similarly reliable
      methods. These results strongly suggest that the proposed method provides a
      valuable contribution to the automated prediction of protein catalytic functions.
      The CatFam databases and the database search program are freely available at
      http://www.bhsai.org/downloads/catfam.tar.gz.

PMID- 18636477
TI  - Coronary vasospasm produces reversible perfusion defects observed during
      adenosine triphosphate stress myocardial single-photon emission computed
      tomography.
AB  - BACKGROUND: Adenosine triphosphate stress thallium-201 single-photon emission
      computed tomography (ATP-SPECT) is useful for diagnosing coronary artery disease
      (CAD), although sometimes false positive results are observed. It has not been
      established whether a coronary spasm is responsible for the false positive
      findings during ATP-SPECT. HYPOTHESIS: We investigated whether coronary spasm is
      one of the factors which produces reversible defects on ATP-SPECT. METHODS:
      Eighty-six patients (mean age: 62 y; 58 men) who underwent both spasm-provocation
      testing by coronary angiography and ATP-SPECT, were selected for the study.
      Patients with coronary narrowing (>30%), myocardial infarction, or heart failure
      were excluded. Patients were divided into 2 groups based on whether the spasm
      provocation test result was positive (vasospastic angina [VSA] group, n = 46) or
      negative (non-VSA group, n = 39). RESULTS: The body mass index was lower in the
      VSA group than in the non-VSA group (p = 0.005). On ATP-SPECT imaging, any type
      of reversible defect was observed more frequently in the VSA group (68%) than in
      the non-VSA group (36%, p = 0.0027). Logistic regression analysis demonstrated
      that the presence of reversible defects was one of the factors accounting for the
      presence of coronary vasospasm (p = 0.0022, R2 = 0.172). CONCLUSIONS: The
      findings suggest that reversible defects on ATP-SPECT imaging are frequently
      present in patients with coronary vasospasm. Coronary spasm may be considered as
      1 of the factors, which produce reversible defects on ATP-SPECT, observed in
      patients with chest symptoms and angiographically normal coronary arteries.

PMID- 18636478
TI  - Two-stage analysis for gene-environment interaction utilizing both case-only and
      family-based analysis.
AB  - The case-only study and family-based study are two popular study designs for
      detecting gene-environment interactions. It is well known that the case-only
      analysis is efficient, but its validity relies crucially on the assumption of
      gene-environment independence in the study population. In contrast, the family
      based analysis is robust to the violation of such an assumption, but is less
      efficient. We propose a two-stage study design for detecting gene-environment
      interactions, where a case-only study is performed at the first stage, and a case
      parent/case-sibling study is performed at the second stage on a random subsample
      of the first-stage case sample as well as their parents/unaffected siblings.
      Statistical inference procedures are developed for the proposed two-stage study
      designs, which not only preserve the robustness property of the family-based
      analysis, but also utilize information from the case-only analysis to enhance
      estimation efficiency and testing power. Simulation results reveal both the
      robustness and efficiency of the proposed strategies.

PMID- 18636481
TI  - Comparative study of simple versus complex stenting of coronary artery
      bifurcation lesions in daily practice in Chinese patients.
AB  - BACKGROUND: Recently, several randomized and controlled trials have demonstrated
      great advantages of a drug-eluting stent (DES) with respect to significant
      reduction in restenosis and recurrence of symptoms, and improvement in clinical
      outcomes after percutaneous coronary intervention (PCI). Little is known about
      the comparative effects of the 1-DES plus the kissing balloon technique with the
      2-DES for bifurcation angioplasty in a Chinese population. METHODS: From April
      2004 to June 2006, 566 consecutive Chinese patients underwent DES implantation
      for true bifurcation lesions, including 346 1-DES with the kissing balloon
      technique (300 male, 57.7 +/- 11.5 y old) and 220 2-DES (183 male, 58.1 +/- 10.7
      y old) were analyzed. Clinical and angiographic follow-up was performed after 7
      mo. RESULTS: The major adverse cardiac event (MACE) rates were higher in the 2
      DES group than in the 1-DES group (5.5% versus 2.0%; p = 0.032), which was mainly
      contributed to by acute myocardial infarction (AMI) (4.5% versus 1.4%; p =
      0.032), rather than death and target lesion revascularization (TLR) (0% versus
      0.5%; p = 0.389, 1.4% versus 2.7%; p = 0.352). Stent thrombosis rates were higher
      in the 2-DES group than in the 1-DES group (0.6% versus 2.7%; p = 0.042), except
      for 1 late-stent thrombosis in the 2-DES group, and all of them were subacute
      stent thrombosis (2 in the 1-DES group and 5 in the 2-DES group). The 7 mo
      angiographic follow-up rate was 36.4%. In the main branch there was no difference
      in restenosis rate in the 1-DES group compared with the 2-DES group (9.8% versus
      11.9%; p = 0.652), but in the side branch the restenosis rate was higher in the 1
      DES group (33.6% versus 15.5%; p = 0.004). However, there was no difference in in
      segment late loss between the 2 groups, either in the main or side branch.
      CONCLUSION: Compared with the 2-DES strategy, if a final kissing balloon could be
      achieved, the 1-DES strategy may be more efficient and safe.

PMID- 18636479
TI  - Common genetic influences underlie comorbidity of migraine and endometriosis.
AB  - We examined the co-occurrence of migraine and endometriosis within the largest
      known collection of families containing multiple women with surgically confirmed
      endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic
      female twin pairs. Within the endometriosis families, a significantly increased
      risk of migrainous headache was observed in women with endometriosis compared to
      women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]:
      1.12-2.21, P=0.009). Bivariate heritability analyses indicated no evidence for
      common environmental factors influencing either migraine or endometriosis but
      significant genetic components for both traits, with heritability estimates of 69
      and 49%, respectively. Importantly, a significant additive genetic correlation
      (r(G) = 0.27, 95% CI: 0.06-0.47) and bivariate heritability (h(2)=0.17, 95% CI:
      0.08-0.27) was observed between migraine and endometriosis. Controlling for the
      personality trait neuroticism made little impact on this association. These
      results confirm the previously reported comorbidity between migraine and
      endometriosis and indicate common genetic influences completely explain their co
      occurrence within individuals. Given pharmacological treatments for endometriosis
      typically target hormonal pathways and a number of findings provide support for a
      relationship between hormonal variations and migraine, hormone-related genes and
      pathways are highly plausible candidates for both migraine and endometriosis.
      Therefore, taking into account the status of both migraine and endometriosis may
      provide a novel opportunity to identify the genes underlying them. Finally, we
      propose that the analysis of such genetically correlated comorbid traits can
      increase power to detect genetic risk loci through the use of more specific,
      homogenous and heritable phenotypes.

PMID- 18636482
TI  - Protein production using recombinant yeast in an immobilized-cell-film airlift
      bioreactor.
AB  - A recombinant Saccharomyces cerevisiae C468/pGAC9 (ATCC 20690), which expresses
      Aspergillus awamori glucoamylase gene under the control of the yeast enolase I
      (ENO1) promoter and secretes glucoamylase into the extracellular medium, was used
      as a model system to investigate the effect of cell immobilization on bioreactor
      culture performance. Free suspension cultures in stirred-tank and airlift
      bioreactors confirmed inherent genetic instability of the recombinant yeast. An
      immobilized-cell-film airlift bioreactor was developed by employing cotton cloth
      sheets to immobilize the yeast cells by attachment. Enhanced enzyme productivity
      and production stability in the immobilized-cell system were observed.
      Experimental data indicated that the immobilized cells maintained a higher
      proportion of plasmid-bearing cells for longer periods under continuous
      operation. The higher plasmid maintenance with immobilized cells is possibly due
      to reduced specific growth rate and increased plasmid copy number. Double
      selection pressure was used to select and maintain the recombinant yeast. The
      selected strain showed better production performance than the original strain.
      (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 241-251, 1997.

PMID- 18636480
TI  - Geometric constraints for porphyrin binding in helical protein binding sites.
AB  - Helical bundles which bind heme and porphyrin cofactors have been popular targets
      for cofactor-containing de novo protein design. By analyzing a highly
      nonredundant subset of the protein databank we have determined a rotamer
      distribution for helical histidines bound to heme cofactors. Analysis of the
      entire nonredundant database for helical sequence preferences near the ligand
      histidine demonstrated little preference for amino acid side chain identity,
      size, or charge. Analysis of the database subdivided by ligand histidine rotamer,
      however, reveals strong preferences in each case, and computational modeling
      illuminates the structural basis for some of these findings. The majority of the
      rotamer distribution matches that predicted by molecular simulation of a single
      porphyrin-bound histidine residue placed in the center of an all-alanine helix,
      and the deviations explain two prominent features of natural heme protein binding
      sites: heme distortion in the case of the cytochromes C in the m166 histidine
      rotamer, and a highly prevalent glycine residue in the t73 histidine rotamer.
      These preferences permit derivation of helical consensus sequence templates which
      predict optimal side chain-cofactor packing interactions for each rotamer. These
      findings thus promise to guide future design endeavors not only in the creation
      of higher affinity heme and porphyrin binding sites, but also in the direction of
      bound cofactor geometry.

PMID- 18636483
TI  - Influence of the nature of modifier in the enzymatic activity of chemical
      modified semipurified lipase from Candida rugosa.
AB  - Semipurified lipase of Candida rugosa (CRSL) was subjected to chemical
      modification, and the activities of the modified lipase, in hydrolysis and
      esterification reactions, were examined. The esterification reactions were
      carried out in the absence and presence of isooctane. When the enzyme was
      modified with polyethylene glycol (PEG), two methodologies were studied. The
      activation of PEG with p-NO(2)-phenylchloroformate gives better biocatalysts than
      those obtained with cyanuric chloride-PEG. The chemical modification with PEG
      increases the stability of pure lipases in isooctane at 50 degrees C (extreme
      conditions). The chemically modified enzymes are useful for biotransformations in
      organic solvents. In addition the nitration of tyrosines with tetranitromethane
      was also studied. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 252-260,
      1997.

PMID- 18636484
TI  - Surfactant as modulating agent of enzyme-loaded liposome activity.
AB  - Large phosphatydilcholine unilamellar vesicles appear to be suitable controlled
      and protective delivery systems of beta-galactosidase. Kinetic measurements
      carried out on intact loaded liposomes show that most of the enzyme is entrapped
      inside the liposomes and its activity is latent. Nevertheless, intact liposomes
      also show significant activity, which can be controlled by addition of detergent.
      At sublytic detergent concentrations, liposome enzymatic activity reaches values
      two or three times greater than those of intact liposomes. This increase seems to
      be due to membrane structure modification that also enhances the substrate
      permeability across the bilayer. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 55: 261-266, 1997.

PMID- 18636485
TI  - Enzyme-polyelectrolyte complexes in water-ethanol mixtures: negatively charged
      groups artificially introduced into alpha-chymotrypsin provide additional
      activation and stabilization effects.
AB  - Formation of noncovalent complexes between alpha-chymotrypsin (CT) and a
      polyelectrolyte, polybrene (PB), has been shown to produce two major effects on
      enzymatic reactions in binary mixtures of polar organic cosolvents with water.
      (i) At moderate concentrations of organic cosolvents (10% to 30% v/v), enzymatic
      activity of CT is higher than in aqueous solutions, and this activation effect is
      more significant for CT in complex with PB (5- to 7-fold) than for free enzyme
      (1.5- to 2.5-fold). (ii) The range of cosolvent concentrations that the enzyme
      tolerates without complete loss of catalytic activity is much broader. For
      enhancement of enzyme stability in the complex with the polycation, the number of
      negatively charged groups in the protein has been artificially increased by using
      chemical modification with pyromellitic and succinic anhydrides. Additional
      activation effect at moderate concentrations of ethanol and enhanced resistance
      of the enzyme toward inactivation at high concentrations of the organic solvent
      have been observed for the modified preparations of CT in the complex with PB as
      compared with an analogous complex of the native enzyme. Structural changes
      behind alterations in enzyme activity in water-ethanol mixtures have been studied
      by the method of circular dichroism (CD). Protein conformation of all CT
      preparations has not changed significantly up to 30% v/v of ethanol where
      activation effects in enzymatic catalysis were most pronounced. At higher
      concentrations of ethanol, structural changes in the protein have been observed
      for different forms of CT that were well correlated with a decrease in enzymatic
      activity. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 267-277, 1997.

PMID- 18636486
TI  - Functionalized dendritic polybenzylethers as acid/base buffers for biocatalysis
      in nonpolar solvents.
AB  - A carboxylic acid functionalized dendritic polybenzyl ether has been synthesized
      and used with its sodium salt to generate a novel acid/base buffer soluble in
      nonpolar organic solvents. The effect of different ratios of the two buffer forms
      on the catalytic activity of subtilisin Carlsberg and chymotrypsin was
      investigated in toluene. It was found that reproducible transesterification rates
      were obtained at each molar ratio consistent with a buffering effect. As the
      molar ratio of the sodium salt to acid was increased there was a corresponding
      increase in the catalytic activity of both enzymes although their profiles were
      not identical. This is consistent with a requirement for deprotonation of a
      residue at active site of the enzyme as observed in aqueous solution. The ability
      to alter and precisely control the ionization state of biocatalysts in nonpolar
      solvents may find useful applications for both fundamental studies and in
      syntheses where reactants or products have acid/base properties. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 55: 278-282, 1997.

PMID- 18636487
TI  - Improvement of the total turnover number and space-time yield for
      chloroperoxidase catalyzed oxidation.
AB  - Chloroperoxidase from Caldariomyces fumago was applied for the oxidation of
      indole to oxindole using hydrogen peroxide as the oxidant in aqueous t-butyl
      alcohol medium. Different ways of adding the oxidant, various reactor types, and
      the use of a hydrogen peroxide-stat were compared, resulting in a 20-fold
      increase of the total turnover number (ttn) and space-time yield (sty). The
      highest ttn of >860,000 was obtained in a fed-batch reactor, whereas the highest
      sty of 120 g/(L . d) was reached in a continuously operated enzyme membrane
      reactor. The results were compared to other enzyme systems already established
      for the synthesis of amino acids and carbohydrates. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 55: 283-288, 1997.

PMID- 18636488
TI  - Biomass measurement by inductive permittivity.
AB  - An electrodeless, inductive permittivity probe is shown to reliably indicate
      fermentation biomass. By designing the probe based on electromagnetic induction,
      the electrode polarization artifact-common to electrode-based permittivity
      measurements of conductive solutions-is eliminated. The measurement of viable
      biomass concentration (X(V)) is precise and linear, with negligible interference,
      as shown for two bacteria, two yeasts, and two mammalian cells. The permittivity
      spectra often can be described by the three parameters of the Cole-Cole equation:
      the maximum (low-frequency) permittivity, the characteristic frequency (f(C)),
      and the Cole-Cole alpha. The f(C) and alpha have potential as relative indicators
      of cell size and morphology, respectively. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 289-304, 1997.

PMID- 18636489
TI  - In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae : I.
      Experimental observations.
AB  - The goal of this work was to obtain rapid sampling technique to measure transient
      metabolites in vivo. First, a pulse of glucose was added to a culture of the
      yeast Saccharomyces cerevisiae growing aerobically under glucose limitation.
      Next, samples were removed at 2 to 5 s intervals and quenched using methods that
      depend on the metabolite measured. Extracellular glucose, excreted products, as
      well as glycolytic intermediates (G6P, F6P, FBP, GAP, 3-PG, PEP, Pyr) and
      cometabolites (ATP, ADP, AMP, NAD(+), NADH) were measured using enzymatic or HPLC
      methods. Significant differences between the adenine nucleotide concentrations in
      the cytoplasm and mitochondria indicated the importance of compartmentation for
      the regulation of the glycolysis. Changes in the intra- and extracellular levels
      of metabolites confirmed that glycolysis is regulated on a time scale of seconds.
      (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 305-316, 1997.

PMID- 18636490
TI  - Experimental optimization of a real time fed-batch fermentation process using
      Markov decision process.
AB  - This article describes a methodology that implements a Markov decision process
      (MDP) optimization technique in a real time fed-batch experiment. Biological
      systems can be better modeled under the stochastic framework and MDP is shown to
      be a suitable technique for their optimization. A nonlinear input/output model is
      used to calculate the probability transitions. All elements of the MDP are
      identified according to physical parameters. Finally, this study compares the
      results obtained when optimizing ethanol production using the infinite horizon
      problem, with total expected discount policy, to previous experimental results
      aimed at optimizing ethanol production using a recombinant Escherichia coli fed
      batch cultivation. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 317
      327, 1997.

PMID- 18636491
TI  - Fermentor temperature as a tool for control of high-density perfusion cultures of
      mammalian cells.
AB  - Temperature is a key environmental variable whose potential in animal cell
      fermentor optimization is not yet fully utilized. The scarce literature data
      suggests that reduced fermentor temperature results in an improved viability and
      shear resistance, higher cell density and titer in batch cultures, and reduction
      in glucose/lactate metabolism. Due to the arrest of the cells in the G1 phase,
      the specific growth rate was found to decrease at temperatures below 37.0 degrees
      C. The response of the specific production rate was cell line dependent: in some
      cases it increased 2-to-3-fold, but decreased in other cases. The controlable
      slowdown of cell metabolism at lower temperature can be used in optimization of
      perfusion mammalian cell cultures with several potential advantages, including
      higher cell density in oxygen limited reactors, lower perfusion rate, improved
      product quality, simplified pH control, and others. To evaluate this strategy, a
      series of long-term experiments in 15 L perfusion bioreactors culturing
      recombinant hamster cells at 20.0 x 10(6) cells/mL were conducted. The
      temperature was changed over a range of set points, and maintained at each of
      these for a long period of time. Steady state process data was collected and
      analyzed. The effect of temperature on the following characteristics of the
      perfusion process was studied: cell growth, glucose/lactate metabolism,
      glutamine/ammonia metabolism, cell respiration, cell density at constant oxygen
      transfer rate, proteolytic activity, and product quality (glycosylation and
      molecule fragmentation). The results suggest that temperature is a variable with
      a significant potential in optimization of perfusion cultures. Properly selected
      temperature set point will contribute to the overall improvement of process
      performance. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 328-338,
      1997.

PMID- 18636492
TI  - Pilot scale processing of detergent-based aqueous two-phase systems.
AB  - Detergent based aqueous two-phase systems have several specific properties, e.g.,
      extreme small density differences between the two liquid phases (0.003-0.005
      g/cm(3)), low interfacial tensions (5-10 microN/m) and complex rheological
      behavior of the product containing detergent-rich phase, which make processing
      difficult. We describe the successful separation of these aqueous two-phase
      systems in the pilot scale (1-20 kg) in the presence and absence of microbial
      cells, either by settling under gravity or in centrifugal separators. The
      performance of self-desludging liquid-liquid separators and of a nozzle separator
      was analyzed in detail to judge large scale application. With a feed rate of 16
      L/h, stable operation was possible in the desludging machine. Up to 56 L/h could
      be processed with very close control of the hydrodynamic balance. In a small
      nozzle separator, feed rates of 90 L/h could be realized, but the purity of the
      separated phases and the yield of the top phase was slightly lower than in the
      liquid-liquid separator. The presence of surface-active components in the feed
      may alter the separation characteristics of the phase systems significantly. (c)
      1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 339-347, 1997.

PMID- 18636493
TI  - Kinetic resolution of alpha-methylbenzylamine with omicron-transaminase screened
      from soil microorganisms: application of a biphasic system to overcome product
      inhibition.
AB  - Two microorganisms showing high omicron-transaminase activity (Klebsiella
      pneumoniae JS2F and Bacillus thuringiensis JS64) were screened by the enrichment
      method using (S)-alpha-methylbenzylamine (alpha-MBA) as a sole nitrogen source.
      Optimal carbon and nitrogen sources for enzyme induction and the properties of
      omicron-transaminases were investigated. omicron-Transaminase from B.
      thuringiensis JS64 was highly enantioselective (E = 75.3) for (S)-enantiomer of
      alpha-MBA and showed remarkable stability. However, omicron-transaminase showed
      severe product inhibition by acetophenone. An aqueous/organic two-phase system
      was introduced to overcome this problem. Through solvent screening, cyclohexanone
      and ethyl acetate were selected as the best organic phases. The acetophenone
      extracting capacity of the solvent and the biocompatibility of the solvent to the
      cell were important determinants in the reaction rate at high concentrations of
      alpha-MBA. The reaction rate of omicron-transamination was strongly influenced by
      the volume ratio of organic phase to aqueous phase as well as agitation speed in
      the biphasic mixture. Using the optimal volume ratio (Vorg:Vaq = 1:4) in the
      biphasic system with cyclohexanone, the reaction rate of omicron-transaminase
      under vigorous mixing conditions increased ninefold compared with that in the
      monophasic aqueous system. At the same optimal conditions, using whole cells, 500
      mM alpha-MBA could be resolved successfully to above 95% enantiomeric excess of
      (R)-alpha-MBA with ca. 51% conversion. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 348-358, 1997.

PMID- 18636494
TI  - Polymerase chain reaction engineering.
AB  - A mathematical model for polymerase chain reaction (PCR) is developed, taking
      into account the three steps in this process: melting of DNA; primer annealing;
      and DNA synthesis (polymerization). Activity and deactivation of the polymerase
      enzyme as a function of temperature is incorporated in the kinetic model to get a
      better understanding of the amplification of DNA. Computer simulation of the
      model is carried out to determine the effects of various parameters, such as the
      cycle number, initial DNA concentration (copynumber), initial enzyme
      concentration, extension time, temperature ramp, and enzyme deactivation on the
      DNA generation. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 359-366,
      1997.

PMID- 18636495
TI  - Selection of salt hydrate pairs for use in water control in enzyme catalysis in
      organic solvents.
AB  - The water activities (a(w)) of 13 salt hydrate pairs were determined from vapor
      pressure measurements; a(w) values for a subset were also estimated from a study
      of water transfer to isopropylether. The application of salt hydrates as water
      buffers was investigated in two models: (i) effect of hydration on the initial
      rate of subtilisincatalyzed transesterification of the nitrophenol ester of CBZ
      alanine with butanol; and (ii) effect of hydrates on the equilibrium
      concentrations of reactants in the esterification of dodecanol and decanoic acid,
      catalyzed by lipase. Transfer of ions from salt to enzyme particles was also
      demonstrated. The implications of the results for the successful use of salt
      hydrates as water buffers are discussed. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 367-374, 1997.

PMID- 18636496
TI  - Intracellular kinetics of a growing virus: a genetically structured simulation
      for bacteriophage T7.
AB  - Viruses have evolved to efficiently direct the resources of their hosts toward
      their own reproduction. A quantitative understanding of viral growth will help
      researchers develop antiviral strategies, design metabolic pathways, construct
      vectors for gene therapy, and engineer molecular systems that self-assemble. As a
      model system we examine here the growth of bacteriophage T7 in Escherichia coli
      using a chemical-kinetic framework. Data published over the last three decades on
      the genetics, physiology, and biophysics of phage T7 are incorporated into a
      genetically structured simulation that accounts for entry of the T7 genome into
      its host, expression of T7 genes, replication of T7 DNA, assembly of T7
      procapsids, and packaging of T7 DNA to finally produce intact T7 progeny. Good
      agreement is found between the simulated behavior and experimental observations
      for the shift in transcription capacity from the host to the phage, the
      initiation times of phage protein synthesis, and the intracellular assembly of
      both wild-type phage and a fast-growing deletion mutant. The simulation is
      utilized to predict the effect of antisense molecules targeted to different T7
      mRNA. Further, a postulated mechanism for the down regulation of T7 transcription
      in vivo is quantitatively examined and shown to agree with available data. The
      simulation is found to be a useful tool for exploring and understanding the
      dynamics of virus growth at the molecular level. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 375-389, 1997.

PMID- 18636497
TI  - Site- and branch-specific sialylation of recombinant human interferon-gamma in
      Chinese hamster ovary cell culture.
AB  - Since sialic acid content is known to be a critical determinant of the biological
      properties of glycoproteins, it is essential to characterize and monitor
      sialylation patterns of recombinant glycoproteins intended for therapeutic use.
      This study reports site- and branch-specific differences in sialylation of human
      interferon-gamma (IFN-gamma) derived from Chinese hamster ovary (CHO) cell
      culture. Sialylation profiles were quantitated by reversed-phase HPLC separations
      of the site-specific pools of tryptic glycopeptides representing IFN-gamma's two
      potential N-linked glycosylation sites (i.e., Asn(25) and Asn(97)). Although
      sialylation at each glycosylation site was found to be incomplete, glycans of
      Asn(25) were more heavily sialylated than those of Asn(97). Furthermore,
      Man(alpha1-3) arms of the predominant complex biantennary structures were more
      favorably sialylated than Man(alpha1-6) branches at each glycosylation site. When
      the sialylation profile was analyzed throughout a suspension batch culture,
      sialic acid content at each site and branch was found to be relatively constant
      until a steady decrease in sialylation was observed coincident with loss of cell
      viability. The introduction of a competitive inhibitor of sialidase into the
      culture supernatant prevented the loss of sialic acid after the onset of cell
      death but did not affect sialylation prior to cell death. This finding indicated
      that incomplete sialylation prior to loss of cell viability could be attributed
      to incomplete intracellular sialylation while the reduction in sialylation
      following loss of cell viability was due to extracellular sialidase activity
      resulting from cell lysis. Thus, both intracellular and extracellular processes
      defined the sialic acid content of the final product. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 55: 390-398, 1977.

PMID- 18636498
TI  - Lipase kinetics in organic-water solvent with amphipathic substrate for chiral
      reaction.
AB  - Lipase from Pseudomonas cepacia was used for asymmetric hydrolysis of the
      substrate (+/-)1-chloro-2-acetoxy-3-(1-naphthyloxy)-propane, which is a precursor
      for (S)-(-)-beta-blocker synthesis. Because this substrate is insoluble in water
      and partially soluble in hydrophobic solvents such as hexane and octane, a
      mixture of hydrophilic organic solvents and aqueous buffer was used to study the
      initial reaction rates. Because of the amphipathic nature of the substrate, it
      can remain in three different forms: (1) monomeric (solution); (2) micellar; and
      (3) emulsion, depending on the acetone and substrate concentrations in the
      medium. This behavior is presented in a phase diagram. The enzyme was found to be
      active with micelle as well as emulsion form of the substrate, whereas it showed
      negligible activity with the monomeric form. Michaelis-Menten constants were
      determined experimentally for the emulsion and micellar part of the substrate.
      The initial rate of hydrolysis (v(0)) goes through a maximum with respect to the
      acetone content of the mixture. It is due to the combined effect of various
      factors occurring simultaneously with the increase in acetone content in the
      solvent. These phenomena are discussed based on the interfacial activation of
      lipase, deactivation of the enzyme at very high acetone concentration, and
      increase in critical micelle concentration (CMC) and critical emulsion
      concentration (CEC) with the increase in acetone content in the solvent. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 55: 399-407, 1997.

PMID- 18636499
TI  - Accumulation of lead by Anabaena cylindrica : mathematical modeling and an energy
      dispersive X-ray study.
AB  - The ability of microorganisms to selectively adsorb various heavy metal ions has
      been recognized for over a decade. We have investigated the biosorption of lead
      by an active culture of the cyanobacterium Anabaena cylindrica. Energy dispersive
      X-ray microanalysis was used to evaluate the different uptake mechanisms in the
      various subcellular regions. Three were identified: a very fast adsorption
      mechanism in the cell envelope; a time-dependent deposition reaction on the cell
      surface; and an adsorption mechanism, also time dependent, on the polyphosphate
      body inside the cell. Atomic absorption spectrometry was then used to quantify
      the changes with time of bulk fluid concentrations of lead solutions exposed to
      cyanobacteria. A mass transfer kinetic model was developed which quantitatively
      predicts the concentration of lead in cells of Anabaena cylindrica as a function
      of spatial dimensions and time. The model predictions are consistent with a
      pattern, documented in literature and confirmed by our own experimental evidence,
      of a very fast uptake in the cell envelope and then a longer uptake period inside
      the cell. Our experimental evidence also revealed a time-dependent uptake
      mechanism on the surface of the cells, which is included in the model. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 55: 408-418, 1997.

PMID- 18636500
TI  - Design of expression systems for metabolic engineering: coordinated synthesis and
      degradation of glycogen.
AB  - In metabolic engineering, systems which allow coordinated control of two
      metabolic pathways can be useful. We designed two expression systems and
      demonstrated their application by coordinating glycogen synthesis and
      degradation. The first expression vector pMSW2 expressed the glycogen synthesis
      genes in one operon and the glycogen degradation gene in a separate, coordinately
      regulated operon. The plasmid was designed to switch off expression of the first
      operon and activate expression of the second operon on addition of IPTG. As an
      alternative means to control glycogen synthesis and degradation pathways, we
      constructed expression vector pGTSD100, which contains the native Escherichia
      coli glycogen synthesis and degradation operon under control of the tac promoter.
      Both expression vectors work successfully to control the net synthesis and
      degradation of glycogen. In cultures of the E. coli strain TA3476 carrying the
      plasmid pMSW2, before the addition of IPTG, glycogen continued to accumulate in
      the culture. About three hours after IPTG was added, glycogen levels began to
      decrease. When no IPTG was added to cultures of TA3476:pMSW2, glycogen
      accumulated in the cells as before but the rate of degradation of glycogen was
      much lower. When IPTG was added to TA3476:pMSW2, the total cell protein at the
      end of batch cultivation was approximately 15% higher compared to cultures
      without IPTG addition. The extra biomass was formed during the glycogen
      degradation phase. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 419
      426, 1997.

PMID- 18636501
TI  - Sensor fusion with on-line gas emission multisensor arrays and standard process
      measuring devices in baker's yeast manufacturing process.
AB  - The use of a multisensor array for measuring the emission from a production-scale
      baker's yeast manufacturing process is reported. The sensor array, containing 14
      different gas-sensitive semiconductor devices and an infrared gas sensor, was
      used to monitor the gas emission from a yeast culture bioreactor during fed-batch
      operation. The signal pattern from the sensors was evaluated in relation to two
      key process variables, the cell mass and the ethanol concentrations. Fusion with
      the on-line sensor signals for reactor weight and aeration rate made it possible
      to estimate cell mass and ethanol concentration using computation with
      backpropagating artificial neural nets. Identification of process states with the
      same fusion of sensor signals was realized using principal component analysis.
      (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 427-438, 1997.

PMID- 18636502
TI  - Extension of Sp2/0 hybridoma cell viability through interleukin-6
      supplementation.
AB  - Sp2/0 hybridoma cells die principally by apoptosis in batch culture. We have
      found that cultures of the Sp2/0 hybridoma exhibit increased viability in
      response to interleukin 6 (IL-6) supplementation relative to control cultures
      during serum shiftdown experiments. When shifted from a medium containing 10%
      fetal bovine serum (FBS) to a medium with 1% FBS, IL-6 supplemented cultures
      displayed viabilities and viable cell densities similar to control cultures
      containing 10% FBS. The degree of the survival response induced varied in
      accordance with the severity of the shiftdown, as cells resuspended in a high
      serum medium showed little observable enhancement in viability. The extension in
      culture viability was not accompanied by an observable decrease in growth
      relative to control cultures, indicating that the effect was not a consequence of
      growth inhibition. These results suggest the existence of serum components with
      behavior functionally similar to IL-6, with respect to enhancing cell survival,
      and that under certain experimental conditions IL-6 serves as a survival factor.
      In contrast to the extended viability displayed by cultures supplemented with IL
      6, Sp2/0 cultures transfected with IL-6 cDNA expression vectors displayed a
      growth inhibitory response relative to control cultures. This inhibitory response
      was characterized by an extended lag phase following inoculation, and a decrease
      in batch culture cell yield. The depression in cell yield varied with serum
      concentration, with the largest depression occurring at high serum
      concentrations. We conclude that interactions between components in serum,
      presumably growth factors, and cytokines play an important role in altering the
      behavior of industrially relevant cell lines in culture. (c) 1997 John Wiley &
      Sons, Inc. Biotechnol Bioeng 55: 439-446, 1997.

PMID- 18636503
TI  - Modeling the growth and proteinase A production in continuous cultures of
      recombinant Saccharomyces cerevisiae.
AB  - Overexpression of the homologous protein proteinase A (PrA) in Saccharomyces
      cerevisiae has been achieved by inserting the PrA gene (PEP4) with its own
      promoter on a 2mu multicopy plasmid. With this system the specific PrA production
      rate was found to be described well by a linear function of the oxidative glucose
      metabolism, the reductive glucose metabolism, and the oxidative ethanol
      metabolism, with a significant lower yield resulting from the reductive glucose
      metabolism compared with the oxidative glucose metabolism. To describe the
      experimental data, a simple mathematical model has been set up. The model is
      based on an assumption of a limited respiratory capacity as suggested by
      Sonnleitner and Kappeli but extended to describe production of an extracellular
      protein. The model predicts correctly the critical dilution rate to be between
      0.15 and 0.16 h(-1), the decrease in the biomass yield above the critical
      dilution rate, and the production of proteinase A at different dilution rates.
      Both the experimental data and model simulations suggest that the optimum
      operating conditions for protein production is just at the critical dilution
      rate. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 447-454, 1997.

PMID- 18636504
TI  - Novel preparation method for surfactant-lipase complexes utilizing water in oil
      emulsions.
AB  - A novel preparation method for surfactant-lipase complexes has been developed
      utilizing water in oil emulsions. In order to optimize the preparation
      conditions, we have investigated the effects of several operational parameters on
      the enzymatic activity of the surfactant-lipase complexes in organic media. When
      a nonionic surfactant was employed under optimal preparation conditions [alkaline
      pH 8-10, organic/aqueous = 90/10 (v/v), concentration of surfactant, 10 mM[, the
      surfactant-lipase complex efficiently catalyzed the esterification of benzyl
      alcohol with lauric acid in organic media. The esterification rate of the
      surfactant-lipase complex was increased over 16-fold relative to the native
      powder lipase. Furthermore, the lipase complex showed high storage stability. (c)
      1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 455-460, 1997.

PMID- 18636505
TI  - Improving accuracy and efficiency of blind protein-ligand docking by focusing on
      predicted binding sites.
AB  - The use of predicted binding sites (binding sites calculated from the protein
      structure alone) is evaluated here as a tool to focus the docking of small
      molecule ligands into protein structures, simulating cases where the real binding
      sites are unknown. The resulting approach consists of a few independent docking
      runs carried out on small boxes, centered on the predicted binding sites, as
      opposed to one larger blind docking run that covers the complete protein
      structure. The focused and blind approaches were compared using a set of 77 known
      protein-ligand complexes and 19 ligand-free structures. The focused approach is
      shown to: (1) identify the correct binding site more frequently than blind
      docking; (2) produce more accurate docking poses for the ligand; (3) require less
      computational time. Additionally, the results show that very few real binding
      sites are missed in spite of focusing on only three predicted binding sites per
      target protein. Overall the results indicate that, by improving the sampling in
      regions that are likely to correspond to binding sites, the focused docking
      approach increases accuracy and efficiency of protein ligand docking for those
      cases where the ligand-binding site is unknown. This is especially relevant in
      applications such as reverse virtual screening and structure-based functional
      annotation of proteins.

PMID- 18636506
TI  - Living history-biography: from Boston to Halifax via Ann Arbor, Minneapolis, and
      Seattle.

PMID- 18636507
TI  - Thioredoxin and thioredoxin binding protein 2 in the liver.
AB  - Thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active
      site -Cys-Gly-Pro-Cys- and constitutes a major thiol reducing system. TRX
      protects cells from stress-induced damage through antioxidative, antiapoptotic,
      and anti-inflammatory effect. In animal models, thioacetamide (TAA)-induced acute
      hepatitis and TAA-induced liver fibrosis was attenuated in TRX transgenic (TRXTG)
      mice. Plasma level of TRX is a good marker for hepatitis and nonalcoholic
      steatohepatitis (NASH) in human patients. Recently, we identified TRX binding
      protein 2 (TBP2) in a yeast two-hybrid screening. TBP2 regulates both the
      expression and reducing activity of TRX as well as cell growth. TBP2 knockout
      (TBP2KO) mice showed disorder in lipid metabolism. TBP2 plays a multiple role on
      cell growth and lipid and glucose metabolism. Thus, TRX and TBP2 play important
      roles in the pathophysiology of liver diseases, including NASH, indicating that
      ratio of TRX and TBP2 expression could be a novel marker of liver diseases like
      NASH.

PMID- 18636508
TI  - The mechanism of amyloid-fibril formation by stefin B: temperature and protein
      concentration dependence of the rates.
AB  - Cystatins, a family of structurally related cysteine proteinase inhibitors, have
      proved to be useful model system to study amyloidogenesis. We have extended
      previous studies of the kinetics of amyloid-fibril formation by human stefin B
      (cystatin B) and some of its mutants, and proposed an improved model for the
      reaction. Overall, the observed kinetics follow the nucleation and growth
      behavior observed for many other amyloidogenic proteins. The minimal kinetic
      scheme that best fits measurements of changes in CD and thioflavin T fluorescence
      as a function of protein concentration and temperature includes nucleation
      (modeled as N(I) irreversible transitions with equivalent rates (k(I)), which
      fitted with N(I) = 64), fibril growth and nonproductive oligomerization, best
      explained by an off-pathway state with a rate-limiting escape rate. Three
      energies of activation were derived from global fitting to the minimal kinetic
      scheme, and independently through the fitting of the individual component rates.
      Nucleation was found to be a first-order process within an oligomeric species
      with an enthalpy of activation of 55 +/- 4 kcal mol(-1). Fibril growth was a
      second-order process with an enthalpy of activation (27 +/- 5 kcal mol(-1)),
      which is indistinguishable from that of tetramer formation by cystatins, which
      involves limited conformational changes including proline trans to cis
      isomerization. The highest enthalpy of activation (95 +/- 5 kcal mol(-1) at 35
      degrees C), characteristic of a substantial degree of unfolding as observed prior
      to domain-swapping reactions, equated with the escape rate of the off-pathway
      oligomeric state.

PMID- 18636509
TI  - Embryotoxicity of artesunate in animal species related to drug tissue
      distribution and toxicokinetic profiles.
AB  - BACKGROUND: Injectable artesunate (AS) can cause fetal death and teratogenic
      effects in animals at levels below the human therapeutic dose. Similar toxicity
      has also been found for oral artemisinins in various animal species, but has not
      been found in humans. METHODS: Studies on tissue distribution (5 mg/kg) and
      toxicokinetics (TK, 30 mg/kg x 3) were conducted in pregnant (GD11-13) and non
      pregnant rats. RESULTS: TK profiles of AS showed that the two groups of rats were
      similar after a single AS dose but were significantly different after multiple
      doses. Following a daily dose for 3 days, no change in AS concentration was found
      in the pregnant animals, but a significant concentration decline was seen in the
      non-pregnant rats on day 3. In addition, a higher conversion rate of AS to
      dihydroartemisinin (DHA) was detected in the pregnant rats after either single or
      multiple doses compared to non-pregnant controls. The ratios of AUC(DHA)/AUC(AS)
      were 0.99-1.02 for the pregnant rats and 0.42-0.48 for non-pregnant animals,
      resulting in a total AUC(DHA D1-3) that was about 3.7-fold higher in pregnant
      rats (15,049 ng.h/ml) than in non-pregnant rats (4,015 ng.h/ml). Furthermore, the
      tissue/blood partition coefficients demonstrated that the level of radiolabeled
      AS that was distributed into uterus, placenta, and ovary was 2-4-fold higher than
      in blood. CONCLUSIONS: TK data showed that unchanged AS and DHA in the blood of
      pregnant rats were 1.53- and 3.74-fold, respectively, higher than those of non
      pregnant animals, which all likely relate to the severe embryotoxicity of AS,
      even with a low-dosage regimen in pregnant animals.

PMID- 18636510
TI  - The proteasome and its role in the degradation of oxidized proteins.
AB  - The generation of free radicals and the resulting oxidative modification of cell
      structures are omnipresent in mammalian cells. This includes the permanent
      oxidation of proteins leading to the disruption of the protein structure and an
      impaired functionality. In consequence, these oxidized proteins have to be
      removed in order to prevent serious metabolic disturbances. The most important
      cellular proteolytic system responsible for the removal of oxidized proteins is
      the proteasomal system. For normal functioning, the proteasomal system needs the
      coordinated interaction of numerous components. This review describes the
      fundamental functions of the 20S "core" proteasome, its regulators, and the roles
      of the proteasomal system beyond the removal of oxidized proteins in mammalian
      cells.

PMID- 18636511
TI  - Enhancement of L+-lactic acid production using mycelial flocs of Rhizopus oryzae.
AB  - L(+)-Lactic acid production was enhanced in the culture of Rhizopus oryzae using
      mycelial flocs formed by addition of 3 g/L mineral support and 5 ppm polyethylene
      oxide. By addition of the mineral support, an electrostatic repulsion between
      mycelia increased by 3.5-fold compared to that of mycelia, which allowed a
      dispersed growth of R. oryzae in the early growth phase. In conventional culture
      the morphology of R. oryzae is that of a pellet-like cake, however, when support
      and polyethylene oxide are added to the culture, the morphology of R. oryzae
      takes on a cotton-like appearance. The formation of these cotton-like mycelial
      flocs was induced by the addition of 5 ppm polyethylene oxide into a 14 h culture
      containing the mineral support before the formation of the conventional pellet
      morphology. The cotton-like flocs were also formed in cultures grown in a
      fermentor. This morphology allowed effective mass transfer inside the flocs and
      effective fluidity of culture broth in the reactor. L(+)-Lactic acid
      concentration produced by mycelial flocs in fermentor, with the support and
      polyethylene oxide, was 103.6 g/L with the yield of 0.86 using 120 g/L of glucose
      as the substrate for this cultures without both, the concentration was 65.2 g/L.
      It demonstrates that cotton-like mycelial flocs are the optimal morphology in the
      culture of R. oryzae.

PMID- 18636512
TI  - Unusual salt and solvent dependence of a protease from an extreme halophile.
AB  - An extracellular protease has been purified from the extreme halophile,
      Halobacterium halobium. The irreversible inactivation kinetics of this halophilic
      protease in salt concentrations below 4M consists of autolytic and nonautolytic
      (steady-state denaturation) components. Addition of organic solvents has a
      dramatic effect on enzyme stability in low salt media. For example, in 0.36M
      NaCl, the inactivation rate constant for the nonautolytic component in 20% (v/v)
      ethylene glycol is ca. 3 orders of magnitude lower than in 20% (v/v)
      tetrahydrofuran. Enzyme stability in different aqueous/organic solvent mixtures
      correlates strongly to the salting-out capacity of the solvent. Solvents that act
      to increase the apparent hydrophobicity of the enzyme's core stabilize the enzyme
      in much the same way as salting-out salts. This mechanism is not important for
      the nonhalophilic protease, subtilisin Carlsberg, and demonstrates that
      halophilic enzymes have evolved highly specialized reaction medium requirements.
      Moreover, through the use of organic solvents, it is shown that high
      concentrations of salts are not absolutely necessary for high enzyme stability,
      and this may have important process considerations.

PMID- 18636513
TI  - Adsorption and desorption of pentachlorophenol on cells of Mycobacterium
      chlorophenolicum PCP-1.
AB  - The sorption behavior of pentachlorophenol (PCP) by the Gram-positive bacterium
      Mycobacterium chlorophenolicum PCP-1 was quantitatively characterized in this
      work, with emphasis on the effects of biomass and pH and on the reversibility of
      PCP adsorption. Both the adsorption and desorption of PCP showed a fast kinetic,
      reaching an equilibrium in less than 1.5-min mixing under the experimental
      conditions. For PCP concentrations up to 600 micromol/L no saturation of the
      adsorption was observed and the adsorption isotherms can be adequately described
      by the Freundlich equation. The adsorption capacity (q(ads)) of M.
      chlorophenolicum PCP-1 increased significantly with decreasing biomass in the low
      concentration range (below 0.5 g/L). The biomass concentration merely affected
      the capacity constant K of the Freundlich model while the intensity parameter n
      remained constant. The q(ads) also increased with decreasing pH, particularly at
      acidic pH values. Again, the pH effect was mainly reflected by the change of K.
      Based on these results a correlation for q(ads), in which K is a function of both
      biomass concentration and pH, was obtained to describe the adsorption isotherms
      at different biomass concentrations and pH values. The desorption of PCP was also
      found to be strongly affected by pH. At pH 5.4 the adsorption was almost
      completely irreversible, while a nearly complete desorption was obtained at pH 7.
      The effect of pH on the sorption behavior was found to be related to the
      ionization of PCP. The irreversibly adsorbed PCP is a strict function of
      concentration of undissociated PCP, while the reversibly adsorbed PCP correlates
      well with the concentration of ionic PCP. The irreversible adsorption has a much
      higher adsorption capacity than the reversible adsorption. These findings led to
      the derivation of a semimechanistic model that satisfactorily describes the
      sorption of PCP by M. chlorophenolicum. The results obtained also give clues to
      the patterns and mechanism(s) of PCP adsorption by microbial cells.

PMID- 18636514
TI  - Kinetics of U(VI) reduction by a dissimilatory Fe(III)-reducing bacterium under
      non-growth conditions.
AB  - Dissimilatory metal-reducing microorganisms may be useful in processes designed
      for selective removal of uranium from aqueous streams. These bacteria can use
      U(VI) as an electron acceptor and thereby reduce soluble U(VI) to insoluble
      U(IV). While significant research has been devoted to demonstrating and
      describing the mechanism of dissimilatory metal reduction, the reaction kinetics
      necessary to apply this for remediation processes have not been adequately
      defined. In this study, pure culture Shewanella alga strain BrY reduced U(VI)
      under non-growth conditions in the presence of excess lactate as the electron
      donor. Initial U(VI) concentrations ranged from 13 to 1680 microM. A maximum
      specific U(VI) reduction rate of 2.37 micromole-U(VI)/(mg-biomass h) and Monod
      half-saturation coefficient of 132 microM-U(VI) were calculated from measured
      U(VI) reduction rates. U(VI) reduction activity was sustained at 60% of this rate
      for at least 80 h. The initial presence of oxygen at a concentration equal to
      atmospheric saturation at 22 degrees C delays but does not prevent U(VI)
      reduction. The rate of U(VI) reduction by BrY is comparable or better than rates
      reported for other metal reducing species. BrY reduces U(VI) at a rate that is
      30% of its Fe(III) reduction rate.

PMID- 18636515
TI  - On-line monitoring of glucose in mammalian cell culture using a flow injection
      analysis (FIA) mediated biosensor.
AB  - A flow injection analysis (FIA) biosensor system has been developed for on-line
      determination of glucose during mammalian cell cultivation. The culture sample
      was peristaltically withdrawn from the bioreactor and after cell separation by a
      steam sterilizable ceramic microfilter, the filtrate was continuously fed to the
      FIA mediated-biosensor system at 4 mLh(-1), whereas the cell-containing retentate
      was recirculated to the bioreactor. In the amperometric biosensor system, glucose
      oxidase was covalently immobilized onto a preactivated nylon membrane and
      attached to the sensing area of a platinum working electrode. The enzyme reaction
      was coupled with the mediator 1,1'-dimethylferricinium (DMFe(+))-cyclodextrin
      inclusion complex to recycle the reduced glucose oxidase to its original active
      state. 1,1'-Dimethylferrocene (DMFe) was then reoxidized to DMFe(+) at the
      surface of the platinum electrode poised at + 0.15 V vs silver/silver chloride.
      The FIA mediated-biosensor was linear up to 6 mM glucose, with a detection limit
      of 0.1 mM, and possessed excellent reproducibility (+/- 0.4 %, 95 % confidence
      interval) over 123 repeated analyses during a 62 h continuous operation. The
      immobilized glucose oxidase was stable for up to 7 days when applied to glucose
      measurement during 5-10 day fed-batch cultivation of 293S mammalian cells. The
      results obtained from the mediated-biosensor system compared well with the
      hexokinase and HPLC data.

PMID- 18636516
TI  - Tc(VII) reduction and accumulation by immobilized cells of Escherichia coli.
AB  - Resting cells of Escherichia coli, immobilized in a flow-through bioreactor,
      coupled the oxidation of formate or hydrogen to Tc(VII) reduction and removal
      from solution. Cells, pregrown anaerobically in a hollow-fiber membrane
      bioreactor, were challenged with 50 microM Tc(VII) in a carrier solution of
      phosphate-buffered saline. The radionuclide accumulated within the membrane
      component of the reactor, corresponding to the localization of the cells.
      Negligible Tc removal was noted in a reactor containing a mutant deficient in
      active Tc(VII) reductase, when supplied with formate as an electron donor.
      Formate or hydrogen was supplied as the electron donor for Tc(VII) reduction to
      cells immobilized in reactors operated in transverse (crossflow) and direct (dead
      end filtration) modes, respectively. Flow-rate activity relationships were used
      to compare the performance of the reactors. A flow rate of 2.4 mL h(-1) supported
      the removal of 50% of the Tc from solution in a reactor operated in transverse
      mode with formate as an electron donor. In contrast, a flow rate of 0.7 mL h(-1),
      supported comparable Tc removal when hydrogen was introduced to a reactor
      operated in direct mode. The reduced reactor efficiency, when hydrogen was used
      as an electron donor, could be attributed, in part, to poor delivery of the gas
      to the cells. The biocatalyst was highly stable in the reactor; no loss in
      activity was noted over 200 h of continuous use.

PMID- 18636517
TI  - Kinetic characterization of mass transfer limited biodegradation of a low water
      soluble gas in batch experiments--necessity for multiresponse fitting.
AB  - A method was developed to characterize the kinetics of biodegradation of low
      water soluble gaseous compounds in batch experiments. The degradation of ethene
      by resting Mycobacterium E3 cells was used as a model system. The batch
      degradation data were recorded as the progress curve (i.e., the time course of
      the ethene concentration in the headspace of the batch vessel). The recorded
      progress curves, however, suffered gas:liquid mass transfer limitation. A new
      multiresponse fitting method had to be developed to allow unequivocal
      identification of both the affinity coefficient, K(aff), and the gas:liquid mass
      transfer coefficient, K(l)a, in the batch vessel from the mass transfer limited
      data. Simulation showed that the K(aff) estimate obtained is influenced by the
      dimensionless (volumetric basis) ethene gas:liquid partitioning coefficient (H).
      In the fitting procedure, Monod, Teissier, and Blackman biokinetics were
      evaluated for characterization of the ethene biodegradation process. The fits
      obtained reflected the superiority of the Blackman biokinetic function. Overall,
      it appears that resting Mycobacterium E3 cells metabolizing ethene at 24 degrees
      C have, using Blackman biokinetics, a maximum specific degradation rate, v(max),
      of 10.2 nmol C(2)H(4) mg(-1) CDW min(-1), and an affinity coefficient, K(aff.g),
      expressed in equilibrium gas concentration units, of 61.9 ppm, when H is assumed
      equal to 8.309.

PMID- 18636518
TI  - The extent to which external oxygen transfer limits growth in shake flask culture
      of hairy roots.
AB  - This study demonstrates the effects of oxygen limitations on growth of Atropa
      belladonna hairy roots in 250-mL shake flasks. Exponential growth was observed
      only for the first 6-8 d culture; after this time, growth continued with
      declining specific rate. Increasing the shaking speed and decreasing the medium
      volume improved biomass production and, to some extent, the specific growth rate
      of the roots. Direct enhancement of oxygen delivery, either by periodic exposure
      of the roots to air or oxygen enrichment of the atmosphere, also increased growth
      rates and/or final biomass levels. These results show that oxygen limitations are
      likely to affect biomass production and kinetic measurements in shake flask
      cultures of hairy roots.

PMID- 18636519
TI  - Transient studies of nutrient uptake, growth, and indole alkaloid accumulation in
      heterotrophic cultures of hairy roots of Catharanthus roseus.
AB  - The kinetics of growth, the uptake of macronutrients, and the accumulation of
      indole alkaloids were investigated in long-term, heterotrophically cultured
      transgenic ("hairy") roots of Catharanthus roseus.Tabersonine, ajmalicine, and
      serpentine were monitored over a 70-day period. The doubling time [dry-weight
      (DW) basis] of C. roseus hairy roots in B5/2 nutrients supplemented with 3%
      sucrose was 3.6 days. NH(4)(+), NO(3),(-) and P(i) were depleted sequentially
      from culture medium by hairy roots, while sugars remained undepleted. The growth
      limiting nutrient was inorganic nitrogen, NH(4)(+) and NO(3)(-), with exponential
      phase overall biomass yields of 34.1 and 5.0 g DW/g nutrient, respectively.
      Extracellular pH decreased to 4.8 in early exponential phase of culture growth
      from the initially adjusted value of 5.7, increased subsequently to a maximum of
      7.7 in late exponential phase of growth coincident with the maximum of fresh
      weight (FW)/DW ratio, before decreasing to 5.5-5.0. The organic acids, pyruvate,
      formate, lactate, and succinate were excreted by hairy roots starting in late
      phase of exponential growth, possibly resulting in the late-culture pH decrease.
      Tabersonine accumulation was distinctly growth associated with maximum specific
      and total yields of 1.15 mg/g DW and 5.6 mg/L, respectively, in late-exponential
      phase of growth. Serpentine accumulation was non growth associated with
      increasing specific and total levels in stationary growth phase: 1.3 mg/g DW and
      10.5 mg/L, respectively. The accumulation of ajmalicine also appeared growth
      associated.

PMID- 18636520
TI  - Kinetic studies on hybridoma cells immobilized in fixed bed reactors.
AB  - Cultures with immobilized hybridoma cells were performed in fixed bed systems.
      "Steady state" values for volume-specific substrate uptake and metabolite
      production rates were determined at various perfusion rates and superficial flow
      velocities of the medium within the carrier matrix. Data from fixed bed volumes
      between 50 and 600 ml did not show any difference. The volume-specific glutamine
      and glucose uptake rate turned out to be independent of the superficial flow
      velocity, but decreased with decreasing glutamine and glucose concentration. The
      volume-specific oxygen uptake rate increased with increasing superficial flow
      velocity and substrate concentration, respectively. A similar behavior was
      observed for the ratio between oxygen and glucose uptake rate. The production
      rate for monoclonal antibodies was neither affected by the substrate
      concentration nor by the superficial flow velocity. The metabolic parameters of
      the immobilized cells were put into kinetic equations and compared to those of
      suspended cells. It could be concluded that the metabolism of the immobilized
      cells is determined by the oxygen supply within the macroporous carriers.

PMID- 18636521
TI  - Antiserum inhibition of propagating viruses.
AB  - The design and implementation of controlled environments to continuously culture
      and evolve viruses provides a means to track how their populations respond to
      natural and designed anti-viral agents. We have previously demonstrated how the
      growth of viruses in spreading plaques enables detection and characterization of
      their evolutionary dynamics. Using plaques of phage T7 growing on E. coli as a
      model system, we observe here that velocities of propagation can be readily
      controlled by the level of anti-viral antiserum incorporated into the propagation
      medium. Further, we develop a simple analytic expression for the radial velocity
      of propagation in terms of the microscopic rates of viral amplification, Fickian
      diffusion of the virions and their neutralization by antiserum. Our analysis
      captures the essential dependence of propagation velocity on antiserum
      concentration. This study provides an ex vivo foundation for exploring how
      medically relevant viruses escape suppression by the immune system.

PMID- 18636522
TI  - Production of recombinant bacterial endoglucanase as a co-product with ethanol
      during fermentation using derivatives of Escherichia coli KO11.
AB  - This study demonstrates a new approach to reduce the amount of fungal cellulase
      required for the conversion of cellulose into ethanol. Escherichia coli KO11, a
      biocatalyst developed for the fermentation of hemicellulose syrups, was used to
      produce recombinant endoglucanase as a co-product with ethanol. Seven different
      bacterial genes were expressed from plasmids in KO11. All produced cell
      associated endoglucanase activity. KO11(pLOI1620) containing Erwinia chrysanthemi
      celZ (EGZ) produced the highest activity, 3,200 IU endoglucanase/L fermentation
      broth (assayed at pH 5.2 and 35 degrees C). Recombinant EGZ was solubilized from
      harvested cells by treatment with dilute sodium dodecyl sulfate (12.5 mg/ml, 10
      min, 50 degrees C) and tested in fermentation experiments with commercial fungal
      cellulase (5 filter paper units/g cellulose) and purified cellulose (100 g/L).
      Using Klebsiella oxytoca P2 as the biocatalyst, fermentations supplemented with
      EGZ as a detergent-lysate of KO11(pLOI1620) produced 14%-24% more ethanol than
      control fermentations supplemented with a detergent-lysate of KO11(pUC18). These
      results demonstrate that recombinant bacterial endoglucanase can function with
      fungal cellulase to increase ethanol yield during the simultaneous
      saccharification and fermentation of cellulose.

PMID- 18636523
TI  - Cumulative sedimentation analysis of Escherichia coli debris size.
AB  - A new method to measure Escherichia coli cell debris size after homogenization is
      presented. It is based on cumulative sedimentation analysis under centrifugal
      force, coupled with Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis
      (SDS-PAGE) analysis of sedimented proteins. The effects that fermentation and
      homogenization conditions have on the resulting debris distributions were
      investigated using this method. Median debris size decreased significantly from
      approximately 0.5 microm to 0.3 microm as the number of homogenization passes
      increased from 2 to 10. Under identical homogenization conditions, uninduced host
      cells in stationary phase had a larger debris size than exponential cells after 5
      homogenizer passes. This difference was not evident after 2 or 10 passes,
      possibly because of confounding intact cells and the existence of a minimum
      debris size for the conditions investigated. Recombinant cells containing protein
      inclusion bodies had the smallest debris size following homogenization. The
      method was also used to measure the size distribution of inclusion bodies. This
      result compared extremely well with an independent determination using
      centrifugal disc photosedimentation (CDS), thus validating the method. This is
      the first method that provides accurate size distributions of E. coli debris
      without the need for sample pretreatment, theoretical approximations (e.g.
      extinction coefficients), or the separation of debris and inclusion bodies prior
      to analysis.

PMID- 18636524
TI  - Effect of hypoosmotic stress on hybridoma cell growth and antibody production.
AB  - To investigate the response of hybridoma cells to hypoosmotic stress,
      S3H5/gamma2bA2 and DB9G8 hybridomas were cultivated in the hypoosmolar medium
      [Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% serum] resulting
      from sodium chloride subtraction. Both hybridomas showed similar responses to
      hypoosmotic stress in regard to cell growth and antibody production. The cell
      growth and antibody production at 276 mOsm/kg were comparable to those at 329
      mOsm/kg (standard DMEM). Both cells grew well at 219 mOsm/kg, though their growth
      and antibody production were slightly decreased. When the osmolality was further
      decreased to 168 mOsm/kg, the cell growth did not occur. When subjected to
      hyperosmotic stress, both cells displayed significantly enhanced specific
      antibody productivity (q(Ab)). However, the cells subjected to hypoosmotic stress
      did not display enhanced q(Ab). Taken together, both hyperosmotic and hypoosmotic
      stresses depressed the growth of S3H5/gamma2bA2 and DB9G8 hybridomas. However,
      their response to hypoosmotic stress in regard to q(Ab) was different from that
      to hyperosmotic stress.

PMID- 18636525
TI  - Model of energy uncoupling for substrate-sufficient culture.
AB  - The growth yields (Y(obs)) are greater under substrate-limited conditions than
      those under substrate-sufficient conditions in continuous cultures. This
      indicates that the excess substrate should cause uncoupling between anabolism and
      catabolism, which leads to energy spilling. Although the uncoupling between
      anabolism and catabolism has already been recognized in the microbiology
      literature, how to quantitatively describe such uncoupling remains unclear. Based
      on a balance on substrate reaction, a growth yield model was developed in
      relation to residual substrate concentration for substrate-sufficient continuous
      cultures. On the basis of that yield model, the concept of an uncoupling
      coefficient between anabolism and catabolism is defined in this work. A model
      describing the effect of the residual substrate concentration on the uncoupling
      coefficient of anabolism to catabolism is proposed. This model agrees very well
      with literature data.

PMID- 18636526
TI  - Engineering mRNA stability in E. coli by the addition of synthetic hairpins using
      a 5' cassette system.
AB  - An expression system has been developed for the introduction of DNA cassettes
      into the region between the transcription and translation start sites of a gene
      of interest. This cassette system was used to engineer mRNA stability through the
      introduction of hairpins at the 5' end. A synthetic DNA cassette was designed so
      that the resulting mRNA hairpin would be positioned one nucleotide from the 5'
      mRNA end. The hairpin-containing mRNA exhibited a half-life 3 times that of the
      mRNA with no hairpin, resulting in increases in both mRNA and protein levels.
      These results indicate that it is possible to engineer mRNA stability as an
      additional means of controlling gene expression.

PMID- 18636527
TI  - Mass and lifetime measurements of exotic nuclei in storage rings.
AB  - Mass and lifetime measurements lead to the discovery and understanding of basic
      properties of matter. The isotopic nature of the chemical elements, nuclear
      binding, and the location and strength of nuclear shells are the most outstanding
      examples leading to the development of the first nuclear models. More recent are
      the discoveries of new structures of nuclides far from the valley of stability. A
      new generation of direct mass measurements which allows the exploration of
      extended areas of the nuclear mass surface with high accuracy has been opened up
      with the combination of the Experimental Storage Ring ESR and the FRragment
      Separator FRS at GSI Darmstadt. In-flight separated nuclei are stored in the
      ring. Their masses are directly determined from the revolution frequency.
      Dependent on the half-life two complementary methods are applied. Schottky Mass
      Spectrometry SMS relies on the measurement of the revolution frequency of
      electron cooled stored ions. The cooling time determines the lower half-life
      limit to the order of seconds. For Isochronous Mass Spectrometry IMS the ring is
      operated in an isochronous ion-optical mode. The revolution frequency of the
      individual ions coasting in the ring is measured using a time-of-flight method.
      Nuclides with lifetimes down to microseconds become accessible. With SMS masses
      of several hundreds nuclides have been measured simultaneously with an accuracy
      in the 2 x 10(-7)-range. This high accuracy and the ability to study large areas
      of the mass surface are ideal tools to discover new nuclear structure properties
      and to guide improvements for theoretical mass models. In addition, nuclear half
      lives of stored bare and highly charged ions have been measured. This new
      experimental development is a significant progress since nuclear decay
      characteristics are mostly known for neutral atoms. For bare and highly charged
      ions new nuclear decay modes become possible, such as bound-state beta decay.
      Dramatic changes in the nuclear lifetime have been observed in highly charged
      ions compared to neutral atoms due to blocking of nuclear decay channels caused
      by the modified atomic interaction. High ionization degrees prevail in hot
      stellar matter and thus these experiments have great relevance for the
      understanding of the synthesis of elements in the universe and astrophysical
      scenarios in general.

PMID- 18636528
TI  - Combined haplotype relative risk (CHRR): a general and simple genetic association
      test that combines trios and unrelated case-controls.
AB  - In some genetic association studies, samples contain both parental and unrelated
      controls. Under such scenarios, instead of analyzing only trios using family
      based association tests or only unrelated subjects using a case-control study
      design, Nagelkerke et al. ([2004] Eur. J. Hum. Genet. 12:964-970) and Epstein et
      al. ([2005] Am. J. Hum. Genet. 76:592-608) proposed methods that implemented a
      likelihood ratio test to combine the two different types of data. In this
      article, we put forward a more powerful and simplified strategy to combine trios
      with unrelated subjects based on the haplotype relative risk (HRR) (Falk and
      Rubinstein [1987] Ann. Hum. Genet. 51:227-233). The HRR compares parental marker
      alleles transmitted to an affected offspring to those not transmitted as a test
      for association, a strategy that is similar to a case-control study that compares
      allele frequencies in diseased cases to those of unrelated controls. We prove
      that affected offspring can be pooled with diseased cases and that parental
      controls can be treated as unrelated controls when the trios and unrelated
      subjects are randomly sampled from the same population. Therefore, unrelated
      subjects can be incorporated into the HRR intuitively and effortlessly. For trios
      without complete parental genotypes, we adopted the strategy proposed by (Guo et
      al. [2005a] BMC Genet. 6:S90; [2005b] Hum. Hered. 59: 125-135), which is more
      feasible than the one proposed by Weinberg ([1999] Am. J. Hum. Genet. 64:1186
      1193). In addition, simulation results suggest that the combined haplotype
      relative risk is more powerful than Epstein et al.'s method regardless of the
      disease prevalence in a homogeneous population.

PMID- 18636530
TI  - Small heart syndrome in patients with chronic fatigue syndrome.
AB  - BACKGROUND: Small heart syndrome has previously been reported as neurocirculatory
      asthenia, associated with a small heart shadow on a chest roentgenogram. This is
      characterized as weakness or fatigue even after ordinary exertion, palpitation,
      dyspnea, and fainting, resembling patients with chronic fatigue syndrome (CFS).
      HYPOTHESIS: Small heart syndrome may be prevalent in patients with CFS. METHODS:
      The study population consisted of 56 patients (<50 y of age) with CFS, and 38
      control subjects. Chest roentgenographic, echocardiographic, and physical
      examinations were performed. RESULTS: Small heart syndrome (cardiothoracic ratio
      <or= 42%) was significantly more prevalent in the CFS group (61%) than in the
      control group (24%) (p < 0.01). In CFS patients with a small heart (n = 34),
      narrow chest (88%), orthostatic dizziness (44%), foot coldness (41%), pretibial
      pitting edema (32%), r-kidney palpability (47%), and mitral valve prolapse (29%),
      were all significantly more prevalent than in the control group, and also in the
      CFS patients without small heart syndrome. Echocardiographic examination
      demonstrated significantly smaller values of both the left ventricular (LV) end
      diastolic dimensions and end-systolic, and stroke volume and cardiac indexes in
      CFS with a small heart, as compared with control subjects with a normal heart
      size (42% < cardiothoracic ratio < 50%). CONCLUSIONS: A considerable number of
      CFS patients have a small heart. Small heart syndrome may contribute to the
      development of CFS as a constitutional factor predisposing to fatigue, and may be
      included in the genesis of CFS.

PMID- 18636529
TI  - Haplotype associations with quantitative traits in the presence of complex
      multilocus and heterogeneous effects.
AB  - In genetic mapping of complex traits, scored haplotypes are likely to represent
      only a subset of all causal polymorphisms. At the extreme of this scenario,
      observed polymorphisms are not themselves functional, and only linked to causal
      ones via linkage disequilibrium (LD). We will demonstrate that due to such
      incomplete knowledge regarding the underlying genetic mechanism, the variance of
      a trait may become different between the scored haplotypes. Thus, unequal
      variances between haplotypes may be indicative of additional functional
      polymorphisms affecting the trait. Methods accounting for such haplotype-specific
      variance may also provide an increased power to detect complex associations. We
      suggest ways to estimate and test these haplotypic variance contrasts, and
      incorporate them into the haplotypic tests for association. We further extend
      this approach to data with unknown gametic phase via likelihood-based
      simultaneous estimation of haplotypic effects and their frequencies. We find our
      approach to provide additional power, especially under the following types of
      models: (a) where scored and unobserved variants are epistatically interacting
      with each other; and (b) under heterogeneity models, where multiple unobserved
      mutations are linked to non-functional observed polymorphisms via LD. An
      illustrative example of usefulness of the method is discussed, utilizing analysis
      of multilocus effects within the catechol-O-methyltransferase gene.

PMID- 18636531
TI  - Using virtual patients to improve cardiac examination competency in medical
      students.
AB  - BACKGROUND: Cardiac examination (CE) skills are in decline. Most prior studies
      employed audio recordings, evaluating only one aspect of CE (i.e., auscultation)
      that precluded correlation with visible observations. To address these
      deficiencies, we developed a curriculum using virtual patient examinations
      (VPEs); bedside recordings of patients with visible and audible cardiovascular
      findings presented as interactive multimedia. HYPOTHESIS: The purpose of this
      study was to evaluate whether VPEs improve CE skills, and whether any
      improvements are retained. We assessed CE competency overall and in 4 categories:
      inspection, auscultation, knowledge, and integration of audio and visual skills.
      METHODS: Students (n = 24) undergoing the 8-wk Internal Medicine (IM) clerkship
      rotation and receiving supervised instruction with VPEs (intervention group) were
      compared with students (n = 58) undergoing IM clerkship rotation without
      supplemental CE instruction (control group). The groups were tested at the
      beginning and the end of their rotations. RESULTS: The Intervention group
      improved significantly in overall mean scores: from 58.7 to 73.5 (p = 0.0001).
      The Control group did not improve: from 60.1 to 59.5 (p = 0.788). The
      Intervention group improved inspection, auscultation, and knowledge (all p
      <or=0.02); control group showed no improvement. Fourteen months after the study,
      8 students from the intervention group were re-tested and mean scores improved
      further to 83.6 without additional intervention (p = 0.004); controls showed
      improvement on re-testing, but it was not significant: 65.0 (p = 0.464).
      CONCLUSIONS: Cardiac examination inspection, auscultation, and knowledge improved
      by using VPEs to the level of cardiology fellows. These skills were retained 1 y
      later. The teaching and testing tools emphasizing the bedside use of both sight
      and sound, identify which CE skills needed improvement and additional training.

PMID- 18636532
TI  - Walter Holbrook Gaskell.

PMID- 18636533
TI  - Homer proteins shape Xenopus optic tectal cell dendritic arbor development in
      vivo.
AB  - Considerable evidence suggests that the Homer family of scaffolding proteins
      contributes to synaptic organization and function. We investigated the role of
      both Homer 1b, the constitutively expressed, and developmentally regulated form
      of Homer, and Homer 1a, the activity-induced immediate early gene, in dendritic
      arbor elaboration and synaptic function of developing Xenopus optic tectal
      neurons. We expressed exogenous Homer 1a or Homer 1b in developing Xenopus tectal
      neurons. By collecting in vivo time lapse images of individual, EGFP-labeled and
      Homer-expressing neurons over 3 days, we found that Homer 1b leads to a
      significant decrease in dendritic arbor growth rate and arbor size. Synaptic
      transmission was also altered in developing neurons transfected with Homer 1b.
      Cells expressing exogenous Homer 1b over 3 days had a significantly greater AMPA
      to NMDA ratios, and increased AMPA mEPSC frequency. These data suggest that
      increasing Homer 1b expression increases excitatory synaptic inputs, increases
      synaptic maturation, and slows dendritic arbor growth rate. Exogenous Homer 1a
      expression increases AMPA mEPSC frequency, but did not significantly affect
      tectal cell dendritic arbor development. Changes in the ratio of Homer 1a to
      Homer 1b may signal the neuron that overall activity levels in the cell have
      changed, and this in turn could affect protein interactions at the synapse,
      synaptic transmission, and structural development of the dendritic arbor.

PMID- 18636534
TI  - Pregnancy in severe anorexia nervosa.
AB  - OBJECTIVE: Anorexia nervosa among Arabian girls seems to be rare and pregnancy in
      condition of extreme underweight seems to be rare as well. METHOD: We report the
      case of a 19-year-old Arabian girl living in Italy who referred to an Eating
      Disorder Unit for her anorexic condition. RESULTS: She arrived for a consultation
      when she was at her 33rd week of pregnancy at a Body Mass Index lower than 14.
      CONCLUSION: The present case aims to underline the need of medical and
      psychological attention to pregnancy in anorexia nervosa cases.

PMID- 18636535
TI  - Histological and ultrastructural investigation of early gonad development and sex
      differentiation in Adriatic sturgeon (Acipenser naccarii, Acipenseriformes,
      Chondrostei).
AB  - Gonad development and sex differentiation from embryos to 594-day-old individuals
      were investigated in farmed Acipenser naccarii using light and transmission
      electron microscopy. The migrating primordial germ cells first appear along the
      dorsal wall of the body cavity in embryos 1.5 days before hatching. The gonadal
      ridge, containing a few primary primordial germ cells (PGC-1) surrounded by
      enveloping cells, appears in 16-day-old larvae. At 60 days, the undifferentiated
      gonad is lamellar and PGC-1 multiply, producing PGC-2. In 105-day-old juveniles,
      a distinct germinal area with advanced PGC-2 appears on the lateral side near the
      mesogonium and the first blood vessels are visible. At 180 days, putative ovaries
      with a notched gonadal epithelium and putative testes with a smooth one appear,
      together with adipose tissue on the distal side. In 210-day-old juveniles, active
      proliferation of germ cells begins in the putative ovaries, whereas putative
      testes still contain only a few germ cells. The onset of meiosis and
      reorganization of stromal tissue occurs in ovaries of 292-day-old individuals.
      Ovaries with developed lamellae enclosing early oocyte clusters and follicles
      with perinucleolar oocytes occur at 594 days. Meiotic stages are never found,
      even in anastomozing tubular testes of 594-day-old individuals. Steroid producing
      cells are detected in the undifferentiated gonad and in the differentiated ones
      of both sexes. Anatomical differentiation of the gonad precedes cytological
      differentiation and female differentiation largely precedes that of the male.
      Gonad development and differentiation are also associated with structural changes
      of connective tissue, viz. collagen-rich areas are massive in developing testes
      and reduced in ovaries.

PMID- 18636536
TI  - Femtosecond laser ablation inductively coupled plasma mass spectrometry:
      fundamentals and capabilities for depth profiling analysis.
AB  - Laser ablation coupled to inductively coupled plasma mass spectrometry has become
      a versatile and powerful analytical method for direct solid analysis. The
      applicability has been demonstrated on a wide variety of samples, where major,
      minor, and trace element concentrations or isotope ratio determinations have been
      of interest. The pros and cons of UV-nsec laser ablation have been studied in
      detail, and indicate that aerosol generation, aerosol transport, and aerosol
      excitation-ionization within the ICP contribute to fractionation effects, which
      prevent this method from a more universal application to all matrices and all
      elements. Recent progresses in IR-fs and UV-fs laser ablation coupled to ICP-MS
      have been reported, which increase the inter-matrix and multi-element
      quantification capabilities of this method. These fundamental improvements in LA
      ICP-MS are of significant importance for entering new applications in material
      science and related research fields. In particular, because coatings (conducting
      and non-conducting) consist of single or multilayers of various elemental
      composition and of different thickness (nm-mm range), significant progress in the
      field of depth profiling with fs-laser ablation can be expected. Therefore, in
      depth profile analysis of polymers, semiconductors, and metal sample
      investigations, using ultra-fast laser ablation for sampling and the currently
      achievable figures of merit, are discussed. In this review manuscript, the
      enhanced capabilities of fs-LA-ICP-MS for direct solid sampling are highlighted,
      and it is discussed about current methods used for quantitative analysis and
      depth profiling, the ablation process of UV-ns and UV-fs, the influence of the
      laser beam profile, aerosol structure and transport efficiency, as well as the
      influence of the ICP-MS (e.g., vaporization and ionization efficiency in the
      plasma, and type of mass analyzer).

PMID- 18636537
TI  - Blockage of NF-kappaB by IKKbeta- or RelA-siRNA rather than the NF-kappaB super
      suppressor IkappaBalpha mutant potentiates adriamycin-induced cytotoxicity in
      lung cancer cells.
AB  - Ambiguous roles of genotoxic anticancer therapeutic-induced NF-kappaB activation
      in regulating gene expression (activation or suppression) and apoptosis (anti- or
      pro-apoptosis) have recently been suggested. In order to clarify this controversy
      and determine the usefulness of NF-kappaB blockage for sensitizing anticancer
      therapy, we have systematically investigated the effect of distinct NF-kappaB
      blocking approaches on lung cancer cells' responses to Adriamycin-induced
      cytotoxicity. The results show that Adriamycin-induced NF-kappaB activation
      functions as a transcriptional activator triggering the expression of anti
      apoptotic genes. Blocking NF-kappaB with IKKbeta- or RelA siRNA substantially
      sensitized Adriamycin-induced cytotoxicity, suggesting that the NF-kappaB pathway
      could be a target for sensitizing lung cancer cells to Adriamycin's anticancer
      effect. Surprisingly, although it effectively blocks NF-kappaB activation, the
      IkappaBalpha super-suppressor (IkappaBalphaAA) antagonized Adriamycin-induced
      cell death. Additionally, the induction of death receptor 5 (DR5), which
      contributes to Adriamycin-induced cytotoxicity, was not affected by NF-kappaB
      blockage. Thus, our results suggest that Adriamycin-induced NF-kappaB is a
      transcriptional activator that protects lung cancer cells against apoptosis, and
      IKKbeta- or RelA siRNA rather than IkappaBalphaAA is an appropriate NF-kappaB
      blocking approach for sensitizing lung cancer cells to Adriamycin-induced
      cytotoxicity.

PMID- 18636539
TI  - Cerebral palsy and anorexia nervosa.
AB  - OBJECTIVE: To describe the management of a woman with cerebral palsy and anorexia
      nervosa. METHOD: We carried out a literature search and gained consent and a
      history from the patient. We explored the etiological and ethical issues raised
      in this case. RESULTS: Etiological issues are raised, looking at the interaction
      between physical disability and self-image. Clinical and practical difficulties
      of caring for a patient with physical disability properly on an eating disorder
      unit are discussed, as well as ethical issues concerning mental capacity and the
      use of the mental health act in anorexia nervosa. CONCLUSION: This case reminds
      us again that we can learn much from listening to patients. In this instance,
      service and operational policies on managing disabilities on the unit, were
      shaped by her input.

PMID- 18636538
TI  - Maternal behaviors and restrained eating and body dissatisfaction in young
      children.
AB  - OBJECTIVE: The present study aimed at testing the relations between maternal
      weight concern and maternal encouragement to be thin as perceived by the child,
      and restraint and body dissatisfaction in young children. METHOD: Cross-sectional
      data were collected among 501 children (aged 7-10), using self-reports on
      maternal behaviors, body dissatisfaction, and restraint. Height and weight were
      objectively measured. Model testing was conducted with M+, and multigroup tests
      were conducted to test differences between the sexes, and between younger and
      older children. RESULTS: Associations between the child's perception of maternal
      encouragement to be thin and child body dissatisfaction and restrained eating
      were found, whereas the child's perception of maternal weight concern was
      primarily related to child restrained eating. No sex differences were found, but
      the relations were stronger for the older children. CONCLUSION: Not only in
      girls, but in boys as well the child's perception of maternal behaviors plays a
      role. At primary school age children may become more vulnerable to possible
      maternal influences.

PMID- 18636540
TI  - Factors associated with improvements in readiness for change: low vs. normal BMI
      eating disorders.
AB  - OBJECTIVE: To examine factors associated with improvements in readiness for
      change as a function of body mass index (BMI) in individuals assessed for eating
      disorders treatment. METHOD: Participants (n = 128) completed the Readiness and
      Motivation Interview (RMI) and measures of psychiatric and eating disorder
      symptoms, quality of life, and self-esteem at baseline and at 5-month follow-up.
      RESULTS: Participants whose readiness for change showed improvements in
      psychiatric symptom severity, global self-esteem, and in the importance of
      friendships as a determinant of self-esteem. Only those with a normal baseline
      BMI (20 kg/m(2) or greater) improved in eating disorder symptoms and quality of
      life, and reported increased importance of personal development and decreased
      importance of shape and weight as determinants of self-esteem. CONCLUSION:
      Correlates of readiness differed between low and normal BMI participants,
      suggesting that weight status may be an important variable to consider in
      preparing highly ambivalent individuals for treatment.

PMID- 18636541
TI  - Activity-based anorexia during adolescence does not promote binge eating during
      adulthood in female rats.
AB  - OBJECTIVE: Given the frequency of transition from anorexia nervosa to bulimia
      nervosa, this study investigated whether a history of activity-based anorexia
      (ABA) during adolescence would promote binge eating during adulthood in female
      rats. METHOD: Adolescent rats were given 1-h unlimited access to chow and ad
      libitum access to a running wheel until body weight reached <80%, indicating the
      development of ABA. During adulthood, all groups were given 21 days of access to
      a palatable food for 2 h/day and ad libitum access to chow. RESULTS: During
      adolescence, rats in the ABA paradigm developed increased wheel running and
      decreased food intake, reaching <80% of body weight after 3 days. However, there
      were no significant differences between groups in the amount of binge food
      consumed during adulthood. CONCLUSION: A brief episode of ABA during adolescence
      did not lead to increased binge eating later in life. Longer-term models are
      needed to determine whether a propensity toward binge eating may result from more
      sustained ABA during adolescence.

PMID- 18636542
TI  - Psychological correlates of purging disorder as compared with other eating
      disorders: an exploratory investigation.
AB  - OBJECTIVE: Keel et al. introduced the diagnostic category of purging disorder
      (PD), an eating disorder characterized by recurring purging behaviors in the
      absence of objective binges. The current study sought to investigate
      psychological correlates among individuals with a lifetime diagnosis of PD as
      compared to those with other eating disorders, and those with no eating disorder.
      METHOD: The current sample included 294 ethnically diverse undergraduate women.
      Subjects diagnosed with different types of eating disorders [i.e., anorexia
      nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging
      disorder (PD)] were compared to one another, as well as to individuals with no
      eating disorder on a variety of indices. RESULTS: Women with PD displayed similar
      levels of drive for thinness as women with AN and BED. Individuals with BN and
      BED exhibited anxiety levels significantly higher than those with PD. Those with
      PD displayed levels of impulsivity that were significantly higher than those of
      individuals with AN or BED, but significantly lower than those of individuals
      with BN. They also displayed similar levels of bulimic symptoms as those with AN
      and BED; however, analysis of item 53 on the EDI revealed that those with PD had
      similar levels of purging ideation as those with BN. Women with any eating
      disorder diagnosis were more likely to have a comorbid Axis I disorder than women
      in the non-eating disorder group. CONCLUSION: Our data replicated and extended
      the findings of Keel et al. and gave further support to the validity and
      distinctiveness of PD.

PMID- 18636543
TI  - Food volume effects on intake and appetite in women with binge-eating disorder
      and weight-matched controls.
AB  - OBJECTIVE: Our study examined the effect of food volume on later intake and
      appetite ratings in 15 women with binge eating disorder (BED) and 15 healthy
      control women. METHOD: On nonconsecutive days, lower-volume (250 ml/171 kcal) and
      higher-volume milk-based preloads (500 ml/171 kcal) were served in
      counterbalanced order. Thirty minutes later, appetite ratings and intake at a
      buffet-style test-lunch were assessed. RESULTS: Higher-volume preloads decreased
      hunger, desire to eat, excitement about eating, desire for dessert, and loss of
      control over eating at test meals, relative to lower-volume preloads. Test-meal
      intake was greater among BED participants than controls; intake did not differ by
      preload volume. BED participants' desire to eat, prospective consumption,
      excitement about eating, and desire for meals and desserts were higher than
      controls' ratings. CONCLUSION: Higher-volume foods decreased hunger and related
      appetite ratings. Differences in food intake and appetite between BED and control
      participants provide further evidence for the validity of test meals to assess
      binge eating.

PMID- 18636544
TI  - Chronic anorexia nervosa: a Delphi study to explore practitioners' views.
AB  - OBJECTIVE: Anorexia nervosa (AN) can be an enduring condition. Increasing
      interest in the treatment of long-term cases has occurred over the recent years.
      This study explored healthcare practitioners' views of what constitutes a case of
      chronic AN and their opinions of its treatment. METHOD: A Delphi study was
      conducted, involving members of specialist groups for professionals with an
      interest in eating disorders and delegates from a conference about enduring AN.
      RESULTS: Participants reached agreement and consensus on factors relating to
      weight, behaviors, and cognitions in cases of chronic AN, but did not for the
      importance of duration and number of treatment attempts. Adopting a supportive,
      co-ordinated, and eclectic approach was considered important in the care of these
      patients. CONCLUSION: Results suggest that chronic AN is not an easy term to
      define and that a rehabilitative model for working with this patient group may be
      required.

PMID- 18636545
TI  - Mass spectrometry in systems biology: an overview.
AB  - As an emerging field, systems biology is currently the talk of the town, which
      challenges our philosophy in comprehending biology. Instead of the reduction
      approach advocated in molecular biology, systems biology aims at systems-level
      understanding of correlations among molecular components. Such comprehensive
      investigation requires massive information from the "omics" cascade demanding
      high-throughput screening techniques. Being one of the most versatile analytical
      methods, mass spectrometry has already been playing a significant role at this
      early stage of systems biology. In this review, we documented the advances in
      modern mass spectrometry technologies as well as nascent inventions. Recent
      applications of mass spectrometry-based techniques and methodologies in genomics,
      proteomics, transcriptomics and metabolomics will be further elaborated
      individually. Undoubtedly, more applications of mass spectrometry in systems
      biology can be expected in the near future.

PMID- 18636546
TI  - Relationship between the methylation status of dietary flavonoids and their
      growth-inhibitory and apoptosis-inducing activities in human cancer cells.
AB  - Flavonoids are polyphenolic compounds widely distributed in the plant kingdom.
      Compelling research indicates that flavonoids have important roles in cancer
      chemoprevention and chemotherapy possibly due to biological activities that
      include action through anti-inflammation, free radical scavenging, modulation of
      survival/proliferation pathways, and inhibition of the ubiquitin-proteasome
      pathway. Plant polyphenols including the green tea polyphenol (-)
      epigallocatechin gallate or (-)-EGCG, and the flavonoids apigenin, luteolin,
      quercetin, and chrysin have been shown to inhibit proteasome activity and induce
      apoptosis in human leukemia cells. However, biotransformation reactions to the
      reactive hydroxyl groups on polyphenols could reduce their biological activities.
      Although methylated polyphenols have been suggested to be metabolically more
      stable than unmethylated polyphenols, the practical use of methylated polyphenols
      as cancer preventative agents warrants further investigation. In the current
      study, methylated and unmethylated flavonoids were studied for their proteasome
      inhibitory and apoptosis-inducing abilities in human leukemia HL60 cells.
      Methylated flavonoids displayed sustained bioavailability and inhibited cellular
      proliferation by arresting cells in the G(1) phase. However, they did not act as
      proteasome inhibitors in either an in vitro system or an in silico model and only
      weakly induced apoptosis. In contrast, unmethylated flavonoids exhibited
      inhibition of the proteasomal activity in intact HL60 cells, accumulating
      proteasome target proteins and inducing caspase activation and poly(ADP-ribose)
      polymerase cleavage. We conclude that methylated flavonoids lack potent
      cytotoxicity against human leukemia cells and most likely have limited ability as
      chemopreventive agents.

PMID- 18636547
TI  - Regulation of Wnt/beta-catenin pathway by cPLA2alpha and PPARdelta.
AB  - Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) is a rate-limiting key enzyme
      that releases arachidonic acid (AA) from membrane phospholipid for the production
      of biologically active lipid mediators including prostaglandins, leukotrienes and
      platelet-activating factor. cPLA(2)alpha is translocated to nuclear envelope in
      response to intracellular calcium increase and the enzyme is also present inside
      the cell nucleus; however, the biological function of cPLA(2)alpha in the nucleus
      remains unknown. Here we show a novel role of cPLA(2)alpha for activation of
      peroxisome proliferator-activated receptor-delta (PPARdelta) and beta-catenin in
      the nuclei. Overexpression of cPLA(2)alpha in human cholangiocarcinoma cells
      induced the binding of PPARdelta to beta-catenin and increased their association
      with the TCF/LEF response element. These effects are inhibited by the
      cPLA(2)alpha siRNA and inhibitors as well as by siRNA knockdown of PPARdelta.
      Overexpression of PPARdelta or treatment with the selective PPARdelta ligand,
      GW501516, also increased beta-catenin binding to TCF/LEF response element and
      increased its reporter activity. Addition of AA and GW501516 to nuclear extracts
      induced a comparable degree of beta-catenin binding to TCF/LEF response element.
      Furthermore, cPLA(2)alpha protein is present in the PPARdelta and beta-catenin
      binding complex. Thus the close proximity between cPLA(2)alpha and PPARdelta
      provides a unique advantage for their efficient functional coupling in the
      nucleus, where AA produced by cPLA(2)alpha becomes immediately available for
      PPARdelta binding and subsequent beta-catenin activation. These results depict a
      novel interaction linking cPLA(2)alpha, PPARdelta and Wnt/beta-catenin signaling
      pathways and provide insight for further understanding the roles of these key
      molecules in human cells and diseases.

PMID- 18636548
TI  - Hypoxia-induced modifications in plasma membranes and lipid microdomains in A549
      cells and primary human alveolar cells.
AB  - We evaluated the response to mild hypoxia exposure of A549 alveolar human cells
      and of a continuous alveolar cell line from human excised lungs (A30) exposed to
      5% O(2) for 5 and 24 h. No signs of increased peroxidation and of early apoptosis
      were detected. After 24 h of hypoxia total cell proteins/DNA ratio decreased
      significantly by about 20%. Similarly, we found a decrease in membrane
      phospholipid and cholesterol content. The membrane fluidity assessed by
      fluorescence anisotropy measurements was unchanged. We also prepared the
      detergent resistant membrane fraction (DRM) to analyze the distribution of the
      two types of lipid microdomains, caveolae and lipid rafts. The DRM content of Cav
      1, marker of caveolae, was decreased, while CD55, marker of lipid rafts,
      increased in both cell lines. Total content of these markers in the membranes was
      unchanged indicating remodelling of their distribution between detergent
      resistant and detergent-soluble fraction of the cellular membrane. The changes in
      protein markers distribution did not imply changes in the corresponding mRNA,
      except in the case of Cav-1 for A30 line. In the latter case we found a parallel
      decrease in Cav-1 and in the corresponding mRNA. We conclude that an exposure to
      a mild degree of hypoxia triggers a significant remodelling of the lipid
      microdomains expression, confirming that they are highly dynamic structures
      providing a prompt signalling platform to changes of the pericellular
      microenvironment.

PMID- 18636549
TI  - Quantification of head motion in children during various fMRI language tasks.
AB  - PURPOSE: Head motion during functional MRI scanning can lead to signal artifact,
      a problem often more severe with children. However, the documentation for the
      characteristics of head motion in children during various language functional
      tasks is very limited in the current literature. This report characterizes head
      motion in children during fMRI as a function of age, sex, and task. METHODS: Head
      motion during four different fMRI language tasks was investigated in a group of
      323 healthy children between the age of 5 and 18 years. A repeated measures ANOVA
      analysis was used to study the impact of age, sex, task, and the interaction of
      these factors on the motion. RESULTS: Pediatric subjects demonstrated
      significantly different amounts of head motion during fMRI when different
      language tasks were used. Word-Picture Matching, the only task that involved
      visual engagement, suffered the least amount of motion, which was significantly
      less than in any of the other three tasks; the latter were not significantly
      different from each other. Further examination revealed that the main effect of
      language task on motion was significantly affected by age, sex, and their
      interaction. CONCLUSION: Our results suggest that age, sex, and task are all
      associated with the degree of head motion in children during fMRI experiments.
      Investigators working with pediatric patients may increase their success by using
      task components associated with less motion (e.g., visual stimuli), or by using
      this large scale dataset to estimate the effects of sex and age on motion for
      planning purposes.

PMID- 18636550
TI  - Expression of mitochondrial transcription factor A (TFAM) during porcine
      gametogenesis and preimplantation embryo development.
AB  - Mitochondrial transcription factor A (TFAM) is responsible for stability,
      maintenance, and transcriptional control of mitochondrial DNA (mtDNA). We have
      studied the expression and distribution of TFAM in the gametes and
      preimplantation embryos of the domestic pig (Sus scrofa). We hypothesized that
      TFAM is not present in the boar sperm mitochondria to reduce the possibility of
      paternal mtDNA propagation in the progeny. In contrast, we anticipated that Tfam
      gene is expressed in a developmental stage-dependent manner in porcine oocytes
      and embryos. The appropriate TFAM band of 25 kDa was detected by Western blotting
      in ejaculated boar spermatozoa, as well as in porcine oocytes and zygotes. Boar
      sperm extracts also displayed several bands >25 kDa suggestive of post
      translational modification by ubiquitination, confirmed by affinity purification
      of ubiquitinated proteins. TFAM immunoreactivity was relegated to the sperm tail
      principal piece and sperm head in fully differentiated spermatozoa. The content
      of Tfam mRNA increased considerably from the germinal vesicle to blastocyst stage
      and also between in vitro fertilized and cultured blastocysts compared to in vivo
      derived blastocysts. TFAM protein accumulated in the oocytes during maturation
      and was reduced by proteolysis after fertilization. This pattern was not mirrored
      in parthenogenetically activated oocytes and zygotes reconstructed by SCNT,
      suggesting deviant processing of TFAM protein and transcript after oocyte/embryo
      manipulation. Thus, TFAM may exert a critical role in porcine gametogenesis and
      preimplantation embryo development. Altogether, our data on the role of TFAM in
      mitochondrial function and inheritance have broad implications for cell
      physiology and evolutionary biology.

PMID- 18636551
TI  - Analysis of lesions in patients with unilateral tactile agnosia using
      cytoarchitectonic probabilistic maps.
AB  - We propose a novel methodical approach to lesion analyses involving high
      resolution MR images in combination with probabilistic cytoarchitectonic maps. 3D
      MR images of the whole brain and the manually segmented lesion mask are spatially
      normalized to the reference brain of a stereotaxic probabilistic
      cytoarchitectonic atlas using a multiscale registration algorithm based on an
      elastic model. The procedure is demonstrated in three patients suffering from
      aperceptive tactile agnosia of the right hand due to chronic infarction of the
      left parietal cortex. Patient 1 presents a lesion in areas of the postcentral
      sulcus, Patient 3 in areas of the superior parietal lobule and adjacent
      intraparietal sulcus, and Patient 2 lesions in both regions. On the basis of
      neurobehavioral data, we conjectured degradation of sequential elementary sensory
      information processing within the postcentral gyrus, impeding texture recognition
      in Patients 1 and 2, and disturbed kinaesthetic information processing in the
      posterior parietal lobe, causing degraded shape recognition in the patients 2 and
      3. The involvement of Brodmann areas 4a, 4p, 3a, 3b, 1, 2, and areas IP1 and IP2
      of the intraparietal sulcus was assessed in terms of the voxel overlap between
      the spatially transformed lesion masks and the 50%-isocontours of the
      cytoarchitectonic maps. The disruption of the critical cytoarchitectonic areas
      and the impaired subfunctions, texture and shape recognition, relate as
      conjectured above. We conclude that the proposed method represents a promising
      approach to hypothesis-driven lesion analyses, yielding lesion-function
      correlates based on a cytoarchitectonic model. Finally, the lesion-function
      correlates are validated by functional imaging reference data.

PMID- 18636552
TI  - Role of the hemopexin domain of matrix metalloproteinases in cell migration.
AB  - The biological functions of matrix metalloproteinases (MMPs) extend beyond
      extracellular matrix degradation. Non-proteolytic activities of MMPs are just
      beginning to be understood. Herein, we evaluated the role of proMMPs in cell
      migration. Employing a Transwell chamber migration assay, we demonstrated that
      transfection of COS-1 cells with various proMMP cDNAs resulted in enhancement of
      cell migration. Latent MMP-2 and MMP-9 enhanced cell migration to a greater
      extent than latent MMP-1, -3, -11 and -28. To examine if proteolytic activity is
      required for MMP-enhanced cell migration, three experimental approaches,
      including fluorogenic substrate degradation assay, transfection of cells with
      catalytically inactive mutant MMP cDNAs, and addition of hydroxamic acid-derived
      MMP inhibitors, were employed. We demonstrated that the proteolytic activities of
      MMPs are not required for MMP-induced cell migration. To explore the mechanism
      underlying MMP-enhanced cell migration, structure-function relationship of MMP-9
      on cell migration was evaluated. By using a domain swapping approach, we
      demonstrated that the hemopexin domain of proMMP-9 plays an important role in
      cell migration when examined by a transwell chamber assay and by a phagokinetic
      migration assay. TIMP-1, which interacts with the hemopexin domain of proMMP-9,
      inhibited cell migration, whereas TIMP-2 had no effect. Employing small molecular
      inhibitors, MAPK and PI3K pathways were found to be involved in MMP-9-mediated
      cell migration. In conclusion, we demonstrated that MMPs utilize a non
      proteolytic mechanism to enhance epithelial cell migration. We propose that
      hemopexin homodimer formation is required for the full cell migratory function of
      proMMP-9.

PMID- 18636553
TI  - Shear stress-induced Ets-1 modulates protease inhibitor expression in
      microvascular endothelial cells.
AB  - Elevated shear stress within the skeletal muscle microvasculature is implicated
      in the induction of a longitudinal splitting form of angiogenesis, which is
      characterized by the lack of basement membrane breakage. We investigated whether
      the transcriptional regulator, Ets-1, is responsive to changes in hemodynamic
      forces and if so, whether Ets-1 controls microvascular endothelial cell integrity
      by inducing the expression of inhibitors of matrix degrading proteases. Rats were
      treated with prazosin for 2, 4, and 7 days to increase in microvascular shear
      stress in hindlimb skeletal muscles. In complimentary in vitro experiments, rat
      microvascular skeletal muscle endothelial cells were exposed to laminar shear
      stress (15 dyne/cm(2)) for 0.5, 2, and 24 h. TaqMan PCR analysis of laser
      microdissected capillaries isolated from EDL muscles demonstrated transient
      (after 2 days) induction of Ets-1 gene expression. In cultured cells, a transient
      up-regulation of Ets-1 mRNA was observed after 2 h shear stimulation, accompanied
      by increased phosphorylation of Ets-1 and enhanced Ets-1 DNA binding activity.
      This response was modulated by ERK1/2 and p38 MAP kinases, but was not dependent
      on NOS or COX-2 activity. PAI-1, TIMP-1 and TIMP-3 mRNA were elevated
      significantly in prazosin treated EDL, and in response to shear stimulation in
      vitro. In cultured endothelial cells, Ets-1 RNA interference abolished the shear
      induced increases in Ets-1, PAI-1, TIMP-1, and TIMP-3 mRNA expression. These
      results suggest that enhanced laminar shear stress may act to preserve the
      integrity of microvascular walls in part through Ets-1-dependent induction of
      protease inhibitors.

PMID- 18636554
TI  - Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and
      growth of prostate cancer.
AB  - One of the most life-threatening complications of prostate cancer is skeletal
      metastasis. In order to develop treatment for metastasis, it is important to
      understand its molecular mechanisms. Our work in this field has drawn parallels
      between hematopoietic stem cell and prostate cancer homing to the marrow. Our
      recent work demonstrated that annexin II expressed by osteoblasts and endothelial
      cells plays a critical role in niche selection. In this study, we demonstrate
      that annexin II and its receptor play a crucial role in establishing metastasis
      of prostate cancer. Prostate cancer cell lines migrate toward annexin II and the
      adhesion of prostate cancer to osteoblasts and endothelial cells was inhibited by
      annexin II. By blocking annexin II or its receptor in animal models, short-term
      and long-term localization of prostate cancers are limited. Annexin II may also
      facilitate the growth of prostate cancer in vitro and in vivo by the MAPK
      pathway. These data strongly suggest that annexin II and its receptor axis plays
      a central role in prostate cancer metastasis, and that prostate cancer utilize
      the hematopoietic stem cell homing mechanisms to gain access to the niche.

PMID- 18636555
TI  - Expression of Runx2 transcription factor in non-skeletal tissues, sperm and
      brain.
AB  - Runx2 is a master transcription factor for chondrocyte and osteoblast
      differentiation and bone formation. However expression of Runx2 (by RT-PCR), has
      been reported in non-skeletal tissues such as breast, T cells and testis. To
      better define Runx2 activity in non-skeletal tissues, we examined transgenic (Tg)
      mice expressing LacZ gene under control of 3.0 kb (3 kb Tg) or 1.0 kb (1 kb Tg)
      of the Runx2 distal (P1) promoter, Runx2 LacZ knock-in (Runx2(+/LacZ)) and
      Runx2/P1 LacZ knock-in (Runx2/P1(+/LacZ)). In the Runx2 3 kb Tg mouse, beta
      galactosidase (beta-gal) expression appeared in various non-skeletal tissues
      including testis, skin, adrenal gland and brain. beta-gal expression from both 3
      kb and 1 kb Tg, reflecting activity of the Runx2 promoter, was readily detectable
      in seminiferous tubules of the testis and the epididymis. At the single cell
      level, beta-gal was detected in spermatids and mature sperms not in sertoli or
      Leydig cells. We also detected a positive signal from the Runx2(+/LacZ) and
      Runx2/P1(+/LacZ) mice. Indeed, Runx2 expression was observed in isolated mature
      sperms, which was confirmed by RT-PCR and Western blot analysis. Runx2, however,
      was not related to sex determination and sperm motility. Runx2 mediated beta-gal
      activity is also found robustly in the hippocampus and frontal lobe of the brain
      in Runx2(+/LacZ). Collectively, these results indicate that Runx2 is expressed in
      several non-skeletal tissues particularly sperms of testis and hippocampus of
      brain. It suggests that Runx2 may play an important role in male reproductive
      organ testis and brain.

PMID- 18636556
TI  - PML/RARalpha fusion protein mediates the unique sensitivity to arsenic
      cytotoxicity in acute promyelocytic leukemia cells: Mechanisms involve the
      impairment of cAMP signaling and the aberrant regulation of NADPH oxidase.
AB  - Acute promyelocytic leukemia (APL) cells are characterized by PML/RARalpha fusion
      protein, high responsiveness to arsenic trioxide (ATO)-induced cytotoxicity and
      an abundant generation of reactive oxygen species (ROS). In this study we
      investigated the association among these three features in APL-derived NB4 cells.
      We found that NADPH oxidase-derived ROS generation was more abundant in NB4 cells
      compared with monocytic leukemia U937 cells. By using PR9, a sub-line of U937
      stably transduced with the inducible PML/RARalpha expression vectors, we
      attributed disparities on ROS generation and ATO sensitivity to the occurrence of
      PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher
      NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. On the
      other hand, the basal intensity of cAMP signaling pathway was compared between
      NB4 and U937 as well as between PR9 cells with or without PML/RARalpha,
      demonstrating that PML/RARalpha-expressing cells had an impaired cAMP signaling
      pathway which relieved its inhibitory effect on NADPH oxidase derived ROS
      generation. In summary, the present study demonstrated the correlation of
      PML/RARalpha with cAMP signaling pathway, NADPH oxidase and ROS generation in APL
      cells. PML/RARalpha that bestows NB4 cells various pathological features,
      paradoxically also endows these cells with the basis for susceptibility to ATO
      induced cytotoxcity.

PMID- 18636557
TI  - Insights into functional modulation of catalytic RNA activity.
AB  - RNA molecules play critical roles in cell biology, and novel findings
      continuously broaden their functional repertoires. Apart from their well
      documented participation in protein synthesis, it is now apparent that several
      noncoding RNAs (i.e., micro-RNAs and riboswitches) also participate in the
      regulation of gene expression. The discovery of catalytic RNAs had profound
      implications on our views concerning the evolution of life on our planet at a
      molecular level. A characteristic attribute of RNA, probably traced back to its
      ancestral origin, is the ability to interact with and be modulated by several
      ions and molecules of different sizes. The inhibition of ribosome activity by
      antibiotics has been extensively used as a therapeutical approach, while
      activation and substrate-specificity alteration have the potential to enhance the
      versatility of ribozyme-based tools in translational research. In this review, we
      will describe some representative examples of such modulators to illustrate the
      potential of catalytic RNAs as tools and targets in research and clinical
      approaches.

PMID- 18636561
TI  - Journal of Computational Chemistry. Foreword.

PMID- 18636559
TI  - Molecular dynamics/order parameter extrapolation for bionanosystem simulations.
AB  - A multiscale approach, molecular dynamics/order parameter extrapolation (MD/OPX),
      to the all-atom simulation of large bionanosystems is presented. The approach
      starts with the introduction of a set of order parameters (OPs) automatically
      generated with orthogonal polynomials to characterize the nanoscale features of
      bionanosystems. The OPs are shown to evolve slowly via Newton's equations, and
      the all-atom multiscale analysis (AMA) developed earlier (Miao and Ortoleva, J
      Chem Phys 2006, 125, 44901) demonstrates the existence of their stochastic
      dynamics, which serve as the justification for our MD/OPX approach. In MD/OPX, a
      short MD run estimates the rate of change of the OPs, which is then used to
      extrapolate the state of the system over time that is much longer than the 10(
      14) second timescale of fast atomic vibrations and collisions. The approach is
      implemented in NAMD and demonstrated on cowpea chlorotic mottle virus (CCMV)
      capsid structural transitions (STs). It greatly accelerates the MD code and its
      underlying all-atom description of the nanosystems enables the use of a universal
      interatomic force field, avoiding recalibration with each new application as
      needed for coarse-grained models. The source code of MD/OPX is distributed free
      of charge at https://simtk.org/home/mdopx and a web portal will be available via
      http://sysbio.indiana.edu/virusx.

PMID- 18636562
TI  - The new tumor suppressor genes ING: genomic structure and status in cancer.
AB  - The Inhibitor of Growth 1 (ING1) gene has been identified and characterized as a
      Type-II tumor suppressor gene (TSG). Subsequently, 4 additional members of the
      family were identified by homology search. ING proteins contain a nuclear
      localization sequence (NLS) and a plant homeo domain (PHD) finger motif in their
      C-terminus. These proteins are involved in numerous signaling pathways especially
      in 2 tumor suppressor pathways: apoptosis and senescence. In human tumors,
      several studies have shown that the expression of ING1 is frequently lost or
      downregulated. It occurs most frequently at the RNA level, and thus epigenetics
      mechanism could be involved. We summarize the current knowledge on ING proteins
      functions and their involvement in various signaling pathways. We also review the
      studies that have investigated the ING protein status in human tumors. The
      interest of ING proteins as biomarkers and their role in tumor initiation and
      progression is discussed.

PMID- 18636563
TI  - The predicted impact of vaccination on human papillomavirus infections in
      Australia.
AB  - Vaccines based on human papillomavirus (HPV) 16 and 18 virus-like particles have
      the potential to prevent approximately 70% of cervical cancers. In Australia,
      public vaccination against HPV commenced in April 2007, and includes routine
      vaccination of females aged 12-13 years, and a 2-year school and GP-based catch
      up in females aged 12-26 years. The objectives of this study were to estimate
      initial vaccination coverage rates, to describe current patterns of sexual
      behavior in young females, and to predict the impact of vaccination on HPV16
      infections. We reviewed early coverage data, estimating that coverage in
      2007/2008 will reach 86% (feasible range 67-90%) for 12- to 13-year-old girls,
      with lower rates attained in older females. A review of survey data found that
      the median age of first intercourse in Australian females is 16 years, with
      approximately 90% of women sexually active at 22 years. Using these data, we
      performed an analysis of HPV transmission to predict the impact of vaccination on
      HPV infection rates. The public program is predicted to result in a reduction in
      the age-standardized incidence of HPV16 infections of 56% by 2010 (feasible range
      48-61%), and 92% by 2050 (feasible range 76-95%). Elective vaccination of older
      women and vaccination of males may provide some incremental gains, but the
      benefits to women of vaccinating males will be less if coverage of females
      remains high. In conclusion, the current vaccination program is expected to
      result in a substantial and rapid reduction in the incidence of HPV16 in
      Australia.

PMID- 18636564
TI  - Do both heterocyclic amines and omega-6 polyunsaturated fatty acids contribute to
      the incidence of breast cancer in postmenopausal women of the Malmo diet and
      cancer cohort?
AB  - Heterocyclic amines (HAs), formed when meat and fish are cooked at high
      temperatures, have been linked to mammary gland cancer in rats, and some
      epidemiological studies indicate increased breast cancer risk by consumption of
      well-done meat. The epidemiological evidence linking HAs per se to breast cancer
      is however sparse, especially from prospective studies. Moreover, high-fat diets
      rich in omega-6 polyunsaturated fatty acids (PUFAs) have produced higher
      frequencies of HA-induced mammary gland tumors in rats compared to those fed low
      fat diets. The aim was to evaluate prospectively if intake of HAs is associated
      with breast cancer incidence, and if the association is independent of omega-6
      PUFA intakes. Among women 50 years or older at baseline from the population-based
      prospective Malmo Diet and Cancer cohort (n = 11,699), 430 women were diagnosed
      with incident invasive breast cancer during a mean follow-up of 10.4 years.
      Information on dietary habits was collected by a modified diet history method.
      Cox proportional hazards regression estimated hazard ratios (HRs) and 95%
      confidence intervals (CIs) of breast cancer associated with energy-adjusted
      intakes of HAs and omega-6 PUFA. Intakes of HAs were not associated with breast
      cancer incidence (HR, 0.94; 95% CI, 0.69-1.28, for highest compared to lowest
      quintile). In individuals with low HA intakes, a significant increased risk was
      observed among those with high intakes of omega-6 PUFAs. In conclusion, intakes
      of HAs are not associated with breast cancer incidence in this Swedish cohort,
      but dietary patterns very high in omega-6 PUFA may promote breast cancer
      development.

PMID- 18636565
TI  - Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2)
      mutations.
AB  - Monocarboxylate transporter 8 (MCT8; approved symbol SLC16A2) facilitates
      cellular uptake and efflux of 3,3',5-triiodothyronine (T3). Mutations in MCT8 are
      associated with severe psychomotor retardation, high serum T3 and low 3,3',5'
      triiodothyronine (rT3) levels. Here we report three novel MCT8 mutations. Two
      subjects with the F501del mutation have mild psychomotor retardation with
      slightly elevated T3 and normal rT3 levels. T3 uptake was mildly affected in
      F501del fibroblasts and strongly decreased in fibroblasts from other MCT8
      patients, while T3 efflux was always strongly reduced. Moreover, type 3
      deiodinase activity was highly elevated in F501del fibroblasts, whereas it was
      reduced in fibroblasts from other MCT8 patients, probably reflecting parallel
      variation in cellular T3 content. Additionally, T3-responsive genes were markedly
      upregulated by T3 treatment in F501del fibroblasts but not in fibroblasts with
      other MCT8 mutations. In conclusion, mutations in MCT8 result in a decreased T3
      uptake in skin fibroblasts. The much milder clinical phenotype of patients with
      the F501del mutation may be correlated with the relatively small decrease in T3
      uptake combined with an even greater decrease in T3 efflux. If fibroblasts are
      representative of central neurons, abnormal brain development associated with
      MCT8 mutations may be the consequence of either decreased or increased
      intracellular T3 concentrations.

PMID- 18636566
TI  - Toward automation of flow data analysis.

PMID- 18636568
TI  - Dissecting interacting molecular populations by FRET.

PMID- 18636569
TI  - Application of membrane-based preferential transport to whole broth processing.
AB  - Preferential transport in adsorptive membranes can be used to selectively remove
      biochemicals directly from fermentation broths. During preferential transport, an
      adsorbing solute is selectively transported across the membrane while
      nonadsorbing solutes and cells are retained by the membrane. This technique was
      used to separate lysozyme directly from a feed containing lysozyme, myoglobin,
      and yeast cells. We found that because the oscillatory flows used in preferential
      transport involve strokes that are close to symmetric, they are very efficient in
      alleviating cake formation due to cell deposition on the membrane surface.
      Theoretical results suggest that, by optimizing process variables, preferential
      transport can lead to a continuous concentrated stream of the adsorbing protein.
      (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 581-591, 1997.

PMID- 18636570
TI  - In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: II.
      Mathematical model.
AB  - A mathematical model of glycolysis in Saccharomyces cerevisiae is presented. The
      model is based on rate equations for the individual reactions and aims to predict
      changes in the levels of intra- and extracellular metabolites after a glucose
      pulse, as described in part I of this study. Kinetic analysis focuses on a time
      scale of seconds, thereby neglecting biosynthesis of new enzymes. The model
      structure and experimental observations are related to the aerobic growth of the
      yeast. The model is based on material balance equations of the key metabolites in
      the extracellular environment, the cytoplasm and the mitochondria, and includes
      mechanistically based, experimentally matched rate equations for the individual
      enzymes. The model includes removal of metabolites from glycolysis and TCC for
      biosynthesis, and also compartmentation and translocation of adenine nucleotides.
      The model was verified by in vivo diagnosis of intracellular enzymes, which
      includes the decomposition of the network of reactions to reduce the number of
      parameters to be estimated simultaneously. Additionally, sensitivity analysis
      guarantees that only those parameters are estimated that contribute to systems
      trajectory with reasonable sensitivity. The model predictions and experimental
      observations agree reasonably well for most of the metabolites, except for
      pyruvate and adenine nucleotides. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 55: 592-608, 1997.

PMID- 18636571
TI  - A novel membrane reactor design for controlled studies of interacting populations
      (simulation of the interaction between microorganism and plant suspension
      cultures).
AB  - The design of a reactor in which two interacting cell populations (microorganisms
      and plants) could grow under controlled conditions was considered. In this
      reactor, the cell populations are separated by a membrane which permits semi-in
      vivo study of induced interaction-specific changes in metabolism. In this paper,
      the interaction of suspension culture of Nicotiana tabacum (tobacco) and the
      Oomycete, Phytophthora nicotiana was simulated. The results of the computer
      simulation show the induced metabolic changes as a consequence of the biological
      interaction. The paper introduces a novel approach in the strategy for the study
      of interacting population in suspension cultures. This type of system has
      potential applications in studies of the regulation of secondary metabolism and
      for the production of high values pharmaceuticals. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 55: 609-615, 1997.

PMID- 18636572
TI  - Application of fluid mechanic and kinetic models to characterize mammalian cell
      detachment in a radial-flow chamber.
AB  - The strength of adhesion and dynamics of detachment of murine 3T3 fibroblasts
      from self-assembled monolayers were measured in a radial-flow chamber (RFC) by
      applying models for fluid mechanics, adhesion strength probability distributions,
      and detachment kinetics. Four models for predicting fluid mechanics in a RFC were
      compared to evaluate the accuracy of each model and the significance of inlet
      effects. Analysis of these models indicated an outer region at large radial
      positions consistent with creeping flow, an intermediate region influenced by
      inertial dampening, and an inner region dominated by entrance effects from the
      axially-oriented inlet. In accompanying experiments patterns of the fraction of
      cells resisting detachment were constructed for individual surfaces as a function
      of the applied shear stress and evaluated by comparison with integrals of both a
      normal and a log-normal distribution function. The two functions were equally
      appropriate, yielding similar estimates of the mean strength of adhesion.
      Further, varying the Reynolds number in the inlet, Re(d), between 630 and 1480
      (corresponding to volumetric flow rates between 0.9 and 2.1 mL/s) did not affect
      the mean strength of adhesion. For these same experiments, analysis of the
      dynamics of detachment revealed three temporal phases: 1) rapid detachment of
      cells at the onset of flow, consistent with a first-order homogeneous kinetic
      model; 2) time-dependent rate of detachment during the first 30 sec. of exposure
      to hydrodynamic shear, consistent with the first-order heterogeneous kinetic
      model proposed by Dickinson and Cooper (1995); and 3) negligible detachment,
      indicative of pseudo-steady state after 60 sec. of flow. Our results provide
      rigorous guidelines for the measurement of adhesive interactions between
      mammalian cells and prospective biomaterial surfaces using a RFC. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 55: 616-629, 1997.

PMID- 18636573
TI  - Dynamics of artificially immobilized Nitrosomonas europaea: Effect of biomass
      decay.
AB  - The dynamics of growth and death of immobilized Nitrosomonas europaea were
      studied. For this, the death rate of suspended cells was determined in the
      absence of ammonium or oxygen by following the loss of respiration activity and
      by fluorescein-diacetate (FDA)/lissamine-green staining techniques. The death
      rates obtained (1.06 x 10(-6) s(-1) or 4.97 x 10(-6) s(-1) in the absence of
      oxygen or ammonium, respectively) were incorporated in a dynamic growth model and
      the effects on the performance of the immobilized-cell process illustrated by
      model simulations.These model simulations and experimental validation show that
      if decay of biomass occurs the biomass concentration in the center of the bead
      decreases. As a result, the systems react slower to changes in substrate
      concentrations than if all cells remain viable.To show that cells in the center
      of the bead died, the FDA and lissamine-green staining techniques were adapted
      for immobilized cells. It was shown that biomass decay occurred, especially in
      the center of the bead; the amount of cells decreased there, and the remaining
      cells were all stained with lissamine green indicating cell death. After the
      substrate availability was decreased, also cells near the surface of the bead
      lost their viability. The number of viable cells increased again after increasing
      the substrate concentration as the result of cell multiplication. At low
      substrate concentrations and low hydraulic retention times, as for example in the
      treatment of domestic wastewater, the death rate of cells is thus an important
      parameter for the performance of the immobilized-cell system. (c) 1997 John Wiley
      & Sons, Inc. Biotechnol Bioeng 55: 630-641, 1997.

PMID- 18636574
TI  - High pressure disruption of yeast cells: The use of scale down operations for the
      prediction of protein release and cell debris size distribution.
AB  - Experiments were carried out aimed at establishing the effects of equipment scale
      down on the disruption of Baker's yeast cells in high pressure homogenisers. Data
      are reported on the cell debris particle size distribution (PSD) and on total
      protein release as a function of the applied pressure for two valve geometries
      and three scales of operation covering flow rates of 28, 60 and 280 L/h. A
      comparison of the results from the experiments indicates that over the range of
      parameters investigated both the total protein release and the cell debris PSDs
      are independent of valve geometry and flow rate through the homogeniser. These
      observations are discussed in the light of relevant previous publications. The
      cell debris PSDs have been simulated by using a recently published model and the
      total protein release data are described by the well-established Hetherington
      expression (Hetherington et al., 1971). (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 642-649, 1997.

PMID- 18636575
TI  - Laboratory evaluation of a two-stage treatment system for TCE cometabolism by a
      methane-oxidizing mixed culture.
AB  - The objective of this research was to evaluate several factors affecting the
      performance of a two-stage treatment system employing methane-oxidizing bacteria
      for trichloroethylene (TCE) biodegradation. The system consists of a completely
      mixed growth reactor and a plug-flow transformation reactor in which the TCE is
      cometabolized. Laboratory studies were conducted with continuous growth reactors
      and batch experiments simulating transformation reactor conditions. Performance
      was characterized in terms of TCE transformation capacity (T(C), g TCE/g cells),
      transformation yield (T(Y), g TCE/g CH(4)), and the rate coefficient ratio
      k(TCE)/K(S,TCE) (L/mg-d). The growth reactor variables studied were solids
      retention time (SRT) and nutrient nitrogen (N) concentration. Formate and methane
      were evaluated as potential transformation reactor amendments. Comparison of
      cultures from 2- and 8-day SRT (nitrogen-limited) growth reactors indicated that
      there was no significant effect of growth reactor SRT or nitrogen availability on
      T(C) or T(Y), but N-limited conditions yielded higher k(TCE)/K(S,TCE). The TCE
      cometabolic activity of the 8-day SRT, N-limited growth reactor culture varied
      significantly during a 7-year period of operation. The T(C) and T(Y) of the
      resting cells increased gradually to levels a factor of 2 higher than the initial
      values. The reasons for this increase are unknown. Formate addition to the
      transformation reactor gave higher T(C) and T(Y) for 2-day SRT growth reactor
      conditions and significantly lower T(C), T(Y), and k(TCE)/K(S,TCE) for 8-day SRT
      N-limited conditions. Methane addition to the transformation reactor inhibited
      TCE cometabolism at low TCE concentrations and enhanced TCE cometabolism at high
      TCE concentrations, indicating that the TCE cometabolism in the presence of
      methane does not follow simple competitive inhibition kinetics. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 55: 650-659, 1997.

PMID- 18636576
TI  - Specific ATP and specific oxygen uptake rate in immobilized cell aggregates:
      Experimental results and theoretical analysis using a structured model of
      immobilized cell growth.
AB  - In this work the quality and activity of immobilized Beneckea natriegens have
      been measured using Specific ATP (SATP) [mg (ATP) g(-1) (dry biomass)] and
      Specific Oxygen Uptake Rate (SOUR) [mg O(2) g(-1) (dry biomass) h(-1)]. The cells
      were grown in a 3 L Three Phase Air Lift Bioreactor (TPALB) and were immobilized
      on diatomaceous earth (silica) support particles; sterile conditions were
      employed during the experiment, with n-propanol as the sole carbon source. Two
      sets of experiments were performed, one with varying dilution rate and the other
      with varying inlet substrate concentration. The average SATP and SOUR of the
      immobilized biomass was 3-4 times lower than the values obtained for suspended
      Beneckea natriegens growing at its maximum growth rate. The suspended biomass
      present in the TPALB was generated primarily through attrition from the outer
      layer of the biofilm, and maintained higher levels of SATP and SOUR than the
      immobilized biomass. This result indicates that the immobilized biomass
      quality/activity is higher at the external layer of the biofilm. A structured
      model in which biomass is divided into two compartments, active and inert, was
      used to describe the experimental results. This model predicts the biomass
      quality/activity and substrate concentration distributions in the biofilm. These
      distributions were integrated to give overall values of SATP and SOUR for the
      immobilized biomass which compared favorably with experimental data. The primary
      implication of the results is that the location of immobilized biomass in the
      biofilm affects its biocatalytic activity, and should be taken into account when
      modeling immobilized biomass bioreactors. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 660-673, 1997.

PMID- 18636577
TI  - Trichloroethylene mineralization in a fixed-film bioreactor using a pure culture
      expressing constitutively toluene ortho -monooxygenase.
AB  - An aerobic, single-pass, fixed-film bioreactor was designed for the continuous
      degradation and mineralization of gas-phase trichloroethylene (TCE). A pure
      culture of Burkholderia cepacia PR1(23)(TOM(23C)), a Tn5transposon mutant of B.
      cepacia G4 that constitutively expresses the TCE-degrading enzyme, toluene ortho
      monooxygenase (TOM), was immobilized on sintered glass (SIRANtrade mark carriers)
      and activated carbon. The inert open-pore structures of the sintered glass and
      the strongly, TCE-absorbing activated carbon provide a large surface area for
      biofilm development (2-8 mg total cellular protein/mL carrier with glucose
      minimal medium that lacks chloride ions). At gas-phase TCE concentrations ranging
      from 0.04 to 2.42 mg/L of air and 0.1 L/min of air flow, initial maximum TCE
      degradation rates of 0.007-0.715 nmol/(min mg protein) (equivalent to 8.6-392.3
      mg TCE/L of reactor/day) were obtained. Using chloride ion generation as the
      indicator of TCE mineralization, the bioreactor with activated carbon mineralized
      an average of 6.9-10.3 mg TCE/L of reactor/day at 0.242 mg/L TCE concentration
      with 0.1 L/min of air flow for 38-40 days. Although these rates of TCE
      degradation and mineralization are two- to 200-fold higher than reported values,
      TOM was inactivated in the sintered-glass bioreactor at a rate that increased
      with increasing TCE concentration (e.g., in approximately 2 days at 0.242 mg/L
      and <1 day at 2.42 mg/L), although the biofilter could be operated for longer
      periods at lower TCE concentrations. Using an oxygen probe and phenol as the
      substrate, the activity of TOM in the effluent cells of the bioreactor was
      monitored; the loss of TOM activity of the effluent cells corroborated the
      decrease in the TCE degradation and mineralization rates in the bioreactor.
      Repeated starving of the cells was found to restore TOM activity in the
      bioreactor with activated carbon and extended TCE mineralization by approximately
      34%. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 674-685, 1997.

PMID- 18636578
TI  - Controlled biomass formation and kinetics of toluene degradation in a bioscrubber
      and in a reactor with a periodically moved trickle-bed.
AB  - The kinetics of degradation of toluene from a model waste gas and of biomass
      formation were examined in a bioscrubber operated under different nutrient
      limitations with a mixed culture. The applicability of the kinetics of continuous
      cultivation of the mixed culture was examined for a special trickle-bed reactor
      with a periodically moved filter bed. The efficiency of toluene elimination of
      the bioscrubber was 50 to 57% and depended on the toluene mass transfer as
      evident from a constant productivity of 0.026 g dry cell weight/L . h over the
      dilution rate. Under potassium limitation the biomass productivity was reduced by
      60% to 0.011 g dry cell weight/L . h at a dilution rate of 0.013/h. Conversely,
      at low dilution rates the specific toluene degradation rates increased. Excess
      biomass in a trickle-bed reactor causes reduction of interfacial area and mass
      transfer, and increase in pressure drop. To avoid these disadvantages, the
      trickle-bed was moved periodically and biomass was removed with outflowing
      medium. The concentration of steady state biomass fixed on polyamide beads
      decreased hyperbolically with the dilution rate. Also, the efficiency of toluene
      degradation decreased from 72 to 56% with increasing dilution rate while the
      productivity increased. Potassium limitation generally caused a reduction in
      biomass, productivity, and yield while the specific degradation increased with
      dilution rate. This allowed the application of the principles of the chemostat to
      the trickle-bed reactor described here, for toluene degradation from waste gases.
      (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 686-692, 1997.

PMID- 18636579
TI  - Real-time method for determining the colony-forming cell content of human
      hematopoietic cell cultures.
AB  - Glucose and lactate metabolic rates were evaluated for cultures of cord blood
      (CB) mononuclear cell (MNC), peripheral blood (PB) MNC, and PB CD34(+) cell
      cultures carried out in spinner flasks and in T-flasks in both serum-containing
      and serum-free media. Specific glucose uptake rates (q(gluc), in micromoles per
      cell per hour) and lactate generation rates (q(lac)) correlated with the
      percentage of colony-forming cells (CFC) present in the culture for a broad range
      of culture conditions. Specifically, the time of maximum CFC percentage in each
      culture coincided with the time of maximum q(gluc) and q(lac) in cultures with
      different seeding densities and cytokine combinations. A two-population model
      (Q(lac) = alpha[CFC] + beta([TC] - [CFC ]), where [TC] is total cell
      concentration; Q(lac) is volumetric lactate production rate in micromoles per
      milliliter per hour; alpha is q(lac) for an average CFC; and beta is q(lac) for
      an average non-CFC) was developed to describe lactate production. The model
      described lactate production well for cultures carried out in both T-flasks and
      spinner flasks and inoculated with either PB or CB MNC or PB CD34(+) cells. The
      values for alpha and beta that were derived from the model varied with both the
      inoculum density and the cytokine combination. However, preliminary results
      indicate that cultures carried out under the same conditions from different
      samples with similar initial CD34(+) cell content have similar values for beta
      and beta. These findings suggest that it should be possible to use lactate
      production data to predict the harvest time that corresponds to the maximum
      number of CFC in culture. The ability to harvest ex vivo hematopoietic cultures
      for transplantation when CFC are at a maximum has the potential to speed the rate
      at which immunocompromised patients recover. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 693-700, 1997.

PMID- 18636581
TI  - A model for light distribution and average solar irradiance inside outdoor
      tubular photobioreactors for the microalgal mass culture.
AB  - A mathematical model to estimate the solar irradiance profile and average light
      intensity inside a tubular photobioreactor under outdoor conditions is proposed,
      requiring only geographic, geometric, and solar position parameters. First, the
      length of the path into the culture traveled by any direct or disperse ray of
      light was calculated as the function of three variables: day of year, solar hour,
      and geographic latitude. Then, the phenomenon of light attenuation by biomass was
      studied considering Lambert-Beer's law (only considering absorption) and the
      monodimensional model of Cornet et al. (1900) (considering absorption and
      scattering phenomena). Due to the existence of differential wavelength
      absorption, none of the literature models are useful for explaining light
      attenuation by the biomass. Therefore, an empirical hyperbolic expression is
      proposed. The equations to calculate light path length were substituted in the
      proposed hyperbolic expression, reproducing light intensity data obtained in the
      center of the loop tubes. The proposed model was also likely to estimate the
      irradiance accurately at any point inside the culture. Calculation of the local
      intensity was thus extended to the full culture volume in order to obtain the
      average irradiance, showing how the higher biomass productivities in a
      Phaeodactylum tricornutum UTEX 640 outdoor chemostat culture could be maintained
      by delaying light limitation. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng
      55: 701-714, 1997.

PMID- 18636582
TI  - Effect of agitation intensities on fungal morphology of submerged fermentation.
AB  - Both parallel fermentations with Aspergillus awamori (CBS 115.52) and a
      literature study on several fungi have been carried out to determine a relation
      between fungal morphology and agitation intensity. The studied parameters include
      hyphal length, pellet size, surface structure or so-called hairy length of
      pellets, and dry mass per-wet-pellet volume at different specific energy
      dissipation rates. The literature data from different strains, different
      fermenters, and different cultivation conditions can be summarized to say that
      the main mean hyphal length is proportional to the specific energy dissipation
      rate according to a power function with an exponent of -0.25 +/- 0.08.
      Fermentations with identical inocula showed that pellet size was also a function
      of the specific energy dissipation rate and proportional to the specific energy
      dissipation rate to an exponent of -0.16 +/- 0.03. Based on the experimental
      observations, we propose the following mechanism of pellet damage during
      submerged cultivation in stirred fermenters. Interaction between mechanical
      forces and pellets results in the hyphal chip-off from the pellet outer zone
      instead of the breakup of pellets. By this mechanism, the extension of the hyphae
      or hair from pellets is restricted so that the size of pellets is related to the
      specific energy dissipation rate. Hyphae chipped off from pellets contribute free
      filamentous mycelia and reseed their growth. So the fraction of filamentous
      mycelial mass in the total biomass is related to the specific energy dissipation
      rate as well.To describe the surface morphology of pellets, the hyphal length in
      the outer zone of pellets or the so-called hairy length was measured in this
      study. A theoretical relation of the hairy length with the specific energy
      dissipation rate was derived. This relation matched the measured data well. It
      was found that the porosity of pellets showed an inverse relationship with the
      specific energy dissipation rate and that the dry biomass per-wet-pellet volume
      increased with the specific energy dissipation rates. This means that the tensile
      strength of pellets increased with the increase of specific energy dissipation
      rate. The assumption of a constant tensile strength, which is often used in
      literature, is then not valid for the derivation of the relation between pellet
      size and specific energy dissipation rate. The fraction of free filamentous
      mycelia in the total biomass appeared to be a function of the specific energy
      dissipation in stirred bioreactors. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 55: 715-726, 1997.

PMID- 18636583
TI  - Toxicity and biodegradation of formaldehyde in anaerobic methanogenic culture.
AB  - Formaldehyde is present in several industrial wastewaters including petrochemical
      wastes. In this study, the toxicity and degradability of formaldehyde in
      anaerobic systems were investigated. Formaldehyde showed severe toxicity to an
      acetate enrichment methanogenic culture. As low as 10 mg/L (0.33 mM) of
      formaldehyde in the reactor completely inhibited acetate utilization.
      Formaldehyde, however, was degraded while acetate utilization was inhibited.
      Degradation of formaldehyde (Initial concentration < or =30 mg/L) followed Monod
      model with a rate constant, k, of 0.35-0.46 d(-1). At higher initial
      concentrations (> or =60 mg/L), formaldehyde degradation was inhibited and
      partial degradation was possible. The initial formaldehyde to biomass ratio,
      S(0)/X(0), was useful to predict the degradation potential of high formaldehyde
      concentrations in batch systems. When S(0)/X(0) < or = 0.1, formaldehyde was
      completely degraded with initial concentration of up to 95 mg/L; when S(0)/X(0) >
      or = 0.29, formaldehyde at higher than 60 mg/L was only partially degraded. The
      inhibition of formaldehyde degradation in batch systems could be avoided by
      repeated additions of low concentrations of formaldehyde (up to 30 mg/L).
      Chemostats (14-day retention time) showed degradation of 74 mg/L-d (1110 mg/L) of
      influent formaldehyde with a removal capacity of 164 mg/g VSS-day. A spike of 30
      mg/L (final concentration in the chemostat) formaldehyde to the chemostat caused
      only a small increase in effluent acetate concentration for 3 days. But a spike
      of 60 mg/L (final concentration in the chemostat) formaldehyde to the chemostat
      resulted in a dramatic increase in acetate concentration in the effluent. The
      results also showed that the acetate enrichment culture was not acclimated to
      formaldehyde even after 226 days. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 55: 727-736, 1997.

PMID- 18636584
TI  - Linear scale ultrafiltration.
AB  - Tangential flow filtration has traditionally been scaled up by maintaining
      constant the filtrate volume to membrane surface area ratio, membrane material
      and pore size, channel height, flow path geometry and retentate and filtrate
      pressures. Channel width and the number of channels have been increased to
      provide increased membrane area. Several other parameters, however, have not been
      maintained constant. A new comprehensive methodology for implementation of linear
      scale up and scale down of tangential flow filtration processes has been
      developed. Predictable scale up can only be achieved by maintaining fluid dynamic
      parameters which are independent of scale. Fluid dynamics are controlled by
      operating parameters (feed flow rate, retentate pressure, fed batch ratio and
      temperature), geometry (channel length, height, turbulence promoter and
      entrance/exit design), materials (membrane, turbulence promoter, and encapsulant
      compression), and system geometry (flow distribution). Cassette manufacturing
      procedures and tolerances also play a significant role in achieving scale
      independent performance. Extensive development work in the aforementioned areas
      has resulted in the successful implementation of linear scale up of
      ultrafiltration processes for recovery of human recombinant DNA derived
      pharmaceuticals. A 400-fold linear scale up has been achieved without
      intermediate pilot scale tests. Scale independent performance has a direct impact
      on process yield, protein quality and product economics and is therefore
      particularly important in the biotechnology industry. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 55: 737-746, 1997.

PMID- 18636585
TI  - New patterns of mixed-substrate utilization during batch growth of Escherichia
      coli K12.
AB  - Microbial growth on mixtures of substrates is of considerable engineering and
      biological interest. Most of the work until now has dealt with microbial growth
      on binary mixtures of sugars or polyols. In these cases, it is often found that
      no matter how the inoculum is precultured, only one of the two substrates is
      consumed in the first growth phase, leading to the diauxic growth pattern. The
      goal of the experiments reported here is to investigate growth on mixtures
      containing at least one organic acid. These experiments show that the substrate
      utilization patterns in such mixtures are qualitatively different from the
      diauxic growth pattern. For instance, during growth of Escherichia coli K12 on
      certain binary mixtures of organic acids, the two substrates are utilized
      simultaneously, and the mixed-substrate maximum specific growth rate exceeds the
      single-substrate maximum specific growth rate on either one of the two
      constituent substrates. Furthermore, the very same mixed-substrate maximum
      specific growth and substrate uptake rates are observed no matter how the
      inoculum is precultured. On the other hand, in a mixture of glucose and pyruvate,
      the maximum specific growth rate seems to depend on the preculturing conditions,
      thus suggesting the existence of multiple physiological quasi-steady states. (c)
      1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 747-757, 1997.

PMID- 18636586
TI  - An indirect optimization method for biochemical systems: description of method
      and application to the maximization of the rate of ethanol, glycerol, and
      carbohydrate production in Saccharomyces cerevisiae.
AB  - Three metabolic models for the production of ethanol, glycerol, and carbohydrates
      in yeast are optimized with respect to different production rates. While
      originally nonlinear, all three optimization problems are reduced in such a way
      that methods of linear programming can be used. The optimizations lead to
      profiles of enzyme activities that are compatible with the physiology of the
      cells, which guarantees their viability and fitness, and yield higher rates of
      the desired final end products than the original systems. In order to increase
      ethanol rate production at least three times, six enzymes must be modulated. By
      contrast, when the production of glycerol or carbohydrates is optimized,
      modulation of just one enzyme (in the case of glycerol) or two enzymes (in the
      case of carbohydrates) is necessary to yield significant increases in product
      flux rate. Comparisons of our results with those obtained from other methods show
      great similarities and demonstrate that both are valid methods. The choice of one
      or the other method depends on the question of interest. (c) 1997 John Wiley &
      Sons, Inc. Biotechnol Bioeng 55: 758-772, 1997.

PMID- 18636587
TI  - Kinetic modeling of poly(beta-hydroxybutyrate) production and consumption by
      Paracoccus pantotrophus under dynamic substrate supply.
AB  - The objective of the research was to obtain insights into the behavior of
      microorganisms under feast/famine conditions as often occur in wastewater
      treatment processes. The response of microorganisms to such conditions is the
      accumulation of storage polymers like poly(beta-hydroxybutyrate). The research
      was performed using a pure culture of Paracoccus pantotrophus LMD 94.21. A steady
      state C-limited chemostat culture was switched to batch mode and a pulse of
      acetate was added. As long as external substrate (acetic acid) was present, the
      organism grew and accumulated poly(beta-hydroxybutyrate). After depletion of the
      external substrate, the stored poly(beta-hydroxybutyrate) was used as growth
      substrate. Poly(beta-hydroxybutyrate) accumulation was found to be strongly
      dependent on the growth rate of the organism before the pulse addition of
      acetate. Poly(beta-hydroxybutyrate) accumulation was correlated to the difference
      in maximum acetate uptake rate and the acetate required for growth. Based on the
      interpretation of the experimental results, a metabolically structured model has
      been set up. This model adequately describes the observed kinetics of the
      poly(beta-hydroxybutyrate) formation and consumption. (c) 1997 John Wiley & Sons,
      Inc. Biotechnol Bioeng 55: 773-782, 1997.

PMID- 18636588
TI  - Fed-batch culture of recombinant NS0 myeloma cells with high monoclonal antibody
      production.
AB  - An amplified NS0 cell line transfected with a vector expressing a humanized
      monoclonal antibody (MAb) against CD-18 and glutamine synthetase (GS) was
      cultivated in a 1.5 L fed-batch culture using a serum-free, glutamine-free
      medium. Concentrated solutions of key nutrient components were fed periodically
      using a simple feeding control strategy. Feeding amounts were adjusted daily
      based on the integral of viable cell concentration over time (IVC) and assumed
      constant specific nutrient consumption rates or yields to maintain concentrations
      of the key nutrient components around their initial levels. On-line oxygen uptake
      rate (OUR) measurement was used to aid empirically the adjustment of the feeding
      time points and amounts by inferring time points of nutrient depletion. Through
      effective nutritional control, both cell growth phase and culture lifetime were
      prolonged significantly, resulting in a maximal viable cell concentration of 6.6
      x 10(9) cells/L and a final IVC of 1.6 x 10(12) cells-h/L at 672 h. The final MAb
      concentration reached more than 2.7 g/L. In this fed-batch culture, cellular
      metabolism shifts were repeatedly observed. Accompanying the culture phase
      transition from the exponential growth to the stationary phase, lactate, which
      was produced in the exponential growth phase, became consumed. The time point at
      which this metabolism shift occurred corresponded to that of rapid decrease of
      OUR, which most likely was caused by nutrient depletion. This transition
      coincided with the onset of ammonia, glutamate and glutamine accumulation. With
      removal of the nutrient depletion by increasing the daily nutrient feeding
      amount, OUR recovered and viable cell concentration increased, while cell
      metabolism shifted again. Instead of consumption, lactate became produced again.
      These results suggest close relationships among nutrient depletion, cell
      metabolism transition, and cell death. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 55: 783-792, 1997.

PMID- 18636589
TI  - Cell size distribution as a parameter for the predetermination of exponential
      growth during repeated batch cultivation of CHO cells.
AB  - The routine measurement of the cell size distribution of a Chinese hamster ovary
      (CHO) cell population during a repeated batch process enables the
      predetermination of exponential growth even 24 h before the population enters the
      log phase, due to a short but significantly increased cell size during the lag
      phase. A prolongation of the stationary phase causes to progressive limitation in
      asparagine, serine, and ethanolamine. Such extended limitation influences the
      duration of the following lag phase and obviously induces a synchronization of
      the cell population that can be monitored easily by a fast cell size analyzing
      technique. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 793-797, 1997.

PMID- 18636590
TI  - Water activity and substrate concentration effects on lipase activity.
AB  - Catalytic activity of lipases (from Rhizopus arrhizus, Canadida rugosa, and
      Pseudomonas sp. was studied in organic media, mainly diisopropyl ether. The
      effect of water activity (a(w)) on V(max) showed that the enzyme activity in
      general increased with increasing amounts of water for the three enzymes. This
      was shown both for esterification and hydrolysis reactions catalyzed by R.
      arrhizus lipase. In the esterification reaction the K(m) for the acid substrate
      showed a slight increase with increasing water activities. On the other hand, the
      K(m) for the alcohol substrate increased 10-20-fold with increasing water
      activity. The relative changes in K(m) were shown to be independent of the enzyme
      studied and solvent used. The effect was attributed to the increasing competition
      of water as a nucleophile for the acyl-enzyme at higher water activities. In a
      hydrolysis reaction the K(m) for the ester was also shown to increase as the
      water activity increased. The effect of water in this case was due to the fact
      that increased concentration of one substrate (water), and thereby increased
      saturation of the enzyme, will increase the apparent K(m) of the substrate
      (ester) to be determined. This explained why the hydrolysis rate decreased with
      increasing water activity at a fixed, low ester concentration. The apparent
      V(max) for R. arrhizus lipase was similar in four of six different solvents that
      were tested; exceptions were toulene and trichloroethylene, which showed lower
      values. The apparent K(m) for the alcohol in the solvents correlated with the
      hydrophobicity of the solvent, hydrophobic solvents giving lower apparent K(m).
      (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 798-806, 1997.

PMID- 18636591
TI  - Thermophilic sulphate and sulphite reduction in lab-scale gas-lift reactors using
      H(2) and CO(2) as energy and carbon source.
AB  - Feasibility of thermophilic (55 degrees C) sulphate and sulphite reduction with
      H(2) and CO(2) gas-mixtures was studied in gas-lift reactors, which contained
      pumice particles as carrier material. Particular attention was paid to biomass
      retention and the competition between hydrogenotrophic sulphate-reducers and
      other hydrogenotrophic thermophiles. A model medium with defined mineral
      nutrients was used.The results of the experiments clearly demonstrate that
      sulphate conversion rates up to 7.5 g SO(4) (2-)/L per day can be achieved. With
      sulphite, a reduction rate of 3.7 g S/L per day was obtained, which equals a
      sulphate conversion rate of 11.1 g SO(4) (2-)/L per day. Under the applied
      conditions, a strong competition for hydrogen between hydrogenotrophic sulphate
      reducers, tentatively designated as Desulfotomaculum sp., and hydrogenotrophic
      methanogens was observed. The outcome of the competition could not be predicted.
      Growth of the mixed culture was totally inhibited at an H(2)S concentration of
      250 mg/L. Poor attachment of sulphate-reducing bacteria was observed in all
      experiments. The biomass concentration did not exceed 1.2 g/L, despite the
      presence of 50 g/L of pumice. The reason for this phenomenon remains to be
      understood. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 807-814, 1997.

PMID- 18636592
TI  - Application of self-cycling fermentation technique to the production of poly-beta
      hydroxybutyrate.
AB  - The production of poly-beta-hydroxybutyrate (PHB) by Alcaligenes eutrophus DSM
      545 in a cyclone bioreactor was compared using various culture methods: batch,
      fed-batch, and self-cycling fermentation (SCF) with and without extended periods
      of nutrient deprivation. SCF is a semi-continuous method that results in a
      nutrient limitation for every successive generation of cells and, therefore, may
      have advantages for products whose formation follow secondary metabolite
      kinetics. Use of the SCF technique without extended nutrient deprivation produced
      a PHB concentration of 1.2 g L(-1) as 40% of the biomass dry weight. With
      nitrogen deprivation for 4 or 6 h, the concentration of PHB decreased when
      compared to the standard SCF technique. However, nitrogen deprivation periods of
      8 h resulted in an increase in PHB concentration to 2.7 g L(-1) or 59% of the
      biomass dry weight. The nutrient cycling may act to repress PHB accumulation
      during periods of nitrogen deprivation, unless a time threshold has been reached,
      after which PHB accumulation occurs as in normal batch culture. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 55: 815-820, 1997.

PMID- 18636593
TI  - Effect of substrate concentration and nitrate inhibition on product release and
      heavy metal removal by a Citrobacter sp.
AB  - A Citrobacter sp. accumulates heavy metals as cell-bound metal phosphates,
      utilizing phosphate released by the enzymatic cleavage of a phosphomonoester
      substrate. The effect of increased substrate (glycerol 2-phosphate, G2P)
      concentration on phosphate release and heavy metal accumulation was evaluated
      using a stirred tank reactor (STR) and a plug flow reactor (PFR). A significant
      improvement in metal removal was achieved with increased substrate concentration
      using immobilized Citrobacter cells in the PFR, which was not observed using free
      cells in the STR. Nitrate is an inhibitor of the Citrobacter phosphatase. This
      inhibition was concentration dependent and reversible. The rate of product
      release was restored by increasing the concentration of substrate (G2P). The
      ratio of rates of phosphate release under two different conditions (different
      nitrate and G2P concentrations) can be described by a equation developed from
      Michaelis-Menten kinetics. The concentration of substrate required for
      restoration of maximum velocity, V(max), in a batch and continuous-flow system
      can be predicted by substitution and calculation; this was confirmed by an
      experiment in model systems using cell suspensions and polyacrylamide gel
      immobilized cells in a flow-though column. For use in industrial situations it
      may be uneconomical or infeasible to supply additional substrate. Bioreactor
      activity was also restored by increasing the flow residence time, in accordance
      with a Michaelis-Menten-based model to describe removal of lanthanum from nitrate
      supplemented flow in a PFR.

PMID- 18636594
TI  - Modeling isotopomer distributions in biochemical networks using isotopomer
      mapping matrices.
AB  - Within the last decades NMR spectroscopy has undergone tremendous development and
      has become a powerful analytical tool for the investigation of intracellular flux
      distributions in biochemical networks using (13)C-labeled substrates. Not only
      are the experiments much easier to conduct than experiments employing radioactive
      tracer elements, but NMR spectroscopy also provides additional information on the
      labeling pattern of the metabolites. Whereas the maximum amount of information
      obtainable with (14)C-labeled substrates is the fractional enrichment in the
      individual carbon atom positions, NMR spectroscopy can also provide information
      on the degree of labeling at neighboring carbon atom positions by analyzing
      multiplet patterns in NMR spectra or using 2-dimensional NMR spectra. It is
      possible to quantify the mole fractions of molecules that show a specific
      labeling pattern, i.e., information of the isotopomer distribution in metabolite
      pools can be obtained. The isotopomer distribution is the maximum amount of
      information that in theory can be obtained from (13)C-tracer studies. The wealth
      of information contained in NMR spectra frequently leads to overdetermined
      algebraic systems. Consequently, fluxes must be estimated by nonlinear least
      squares analysis, in which experimental labeling data is compared with simulated
      steady state isotopomer distributions. Hence, mathematical models are required to
      compute the steady state isotopomer distribution as a function of a given set of
      steady state fluxes. Because 2(n) possible labeling patterns exist in a molecule
      of n carbon atoms, and each pattern corresponds to a separate state in the
      isotopomer model, these models are inherently complex. Model complexity, so far,
      has restricted usage of isotopomer information to relatively small metabolic
      networks. A general methodology for the formulation of isotopomer models is
      described. The model complexity of isotopomer models is reduced to that of
      classical metabolic models by expressing the 2(n) isotopomer mass balances of a
      metabolite pool in a single matrix equation. Using this approach an isotopomer
      model has been implemented that describes label distribution in primary carbon
      metabolism, i.e., in a metabolic network including the Embden-Meyerhof-Parnas and
      pentose phosphate pathway, the tricarboxylic acid cycle, and selected anaplerotic
      reaction sequences. The model calculates the steady state label distribution in
      all metabolite pools as a function of the steady state fluxes and is applied to
      demonstrate the effect of selected anaplerotic fluxes on the labeling pattern of
      the pathway intermediates.

PMID- 18636595
TI  - Lactic acid fermentation in a recycle batch reactor using immobilized
      Lactobacillus casei.
AB  - Lactic acid production by recycle batch fermentation using immobilized cells of
      Lactobacillus casei subsp. rhamnosus was studied. The culture medium was composed
      of whey treated with an endoprotease, and supplemented with 2.5 g/L of yeast
      extract and 0.18 mM Mn(2+) ions. The fermentation set-up comprised of a column
      packed with polyethyleneimine-coated foam glass particles, Pora-bact A, and
      connected with recirculation to a stirred tank reactor vessel for pH control. The
      immobilization of L. casei was performed simply by circulating the culture medium
      inoculated with the organism over the beads. At this stage, a long lag period
      preceded the cell growth and lactic acid production. Subsequently, for recycle
      batch fermentations using the immobilized cells, the reducing sugar concentration
      of the medium was increased to 100 g/L by addition of glucose. The lactic acid
      production started immediately after onset of fermentation and the average
      reactor productivity during repeated cycles was about 4.3 to 4.6 g/L . h, with
      complete substrate utilization and more than 90% product yield. Sugar consumption
      and lactate yield were maintained at the same level with increase in medium
      volume up to at least 10 times that of the immobilized biocatalyst. The
      liberation of significant amounts of cells into the medium limited the number of
      fermentation cycles possible in a recycle batch mode. Use of lower yeast extract
      concentration reduced the amount of suspended biomass without significant change
      in productivity, thereby also increasing the number of fermentation cycles, and
      even maintained the D-lactate amount at low levels. The product was recovered
      from the clarified and decolorized broth by ion-exchange adsorption.

PMID- 18636596
TI  - Very high-level production and export in Escherichia coli of a cellulose binding
      domain for use in a generic secretion-affinity fusion system.
AB  - A novel expression vector pTugA, previously constructed in our laboratory, was
      modified to provide kanamycin resistance (pTugK) and used to direct the synthesis
      of polypeptides as fusions with the C- or N-terminus of a cellulose binding
      domain which serves as the affinity tag in a novel secretion-affinity fusion
      system. Fed-batch fermentation strategies were applied to production in
      recombinant E. coli TOPP5 of the cellulose binding domain (CBD) from the
      Cellulomonas fimi cellulase Cex. The pTugK expression vector, which codes for the
      Cex leader sequence that directs the recombinant protein to the periplasm of E.
      coli, was shown to remain stable at very high-cell densities. Recombinant cell
      densities in excess of 90 g (dry cell weight)/L were achieved using media and
      feed solutions optimized using a 2(n) factorial design. Optimization of inducer
      (isophenyl-thio-beta-D-galactopyranoside) concentration and the time of induction
      led to soluble, fully active CBD(Cex) production levels in excess of 8 g/L.

PMID- 18636597
TI  - Metabolic and physiological studies of Corynebacterium glutamicum mutants.
AB  - The physiology and central carbon metabolism of Corynebacterium glutamicum was
      investigated through the study of specific disruption mutants. Mutants deficient
      in phosphoenolpyruvate carboxylase (PPC) and/or pyruvate kinase (PK) activity
      were constructed by disrupting the corresponding gene(s) via transconjugation.
      Standard batch fermentations were carried out with these mutants and results were
      evaluated in the context of intracellular flux analysis. The following were
      determined. (a) There is a significant reduction in the glycolytic pathway flux
      in the pyruvate kinase deficient mutants during growth on glucose, also evidenced
      by secretion of dihydroxyacetone and glyceraldehyde. The resulting metabolic
      overflow is accommodated by the pentose phosphate pathway (PPP) acting as
      mechanism for dissimilating, in the form of CO(2), large amounts of accumulated
      intermediates. (b) The high activity through the PPP causes an overproduction of
      reducing power in the form of NADPH. The overproduction of biosynthetic reducing
      power, as well as the shortage of NADPH produced via the tricarboxylic acid cycle
      (as evidenced by a reduced citrate synthase flux), are compensated by an
      increased activity of the transhydrogenase (THD) enzyme catalyzing the reaction
      NADPH + NAD(+)<-->NADP(+) + NADH. The presence of active THD was also confirmed
      directly by enzymatic assays. (c) Specific glucose uptake rates declined during
      the course of fermentation and this decline was more pronounced in the case of a
      double mutant strain deficient in both PPC and PK. Specific ATP consumption rates
      similarly declined during the course of the batch. However, they were
      approximately the same for all strains, indicating that energetic requirements
      for biosynthesis and maintenance are independent of the specific genetic
      background of a strain. The above results underline the importance of
      intracellular flux analysis, not only for producing a static set of intracellular
      flux estimates, but also for uncovering changes occurring in the course of a
      batch fermentation or as result of specific genetic modifications.

PMID- 18636598
TI  - Adhesion and biofilm development on suspended carriers in airlift reactors:
      hydrodynamic conditions versus surface characteristics.
AB  - Adhesion and biofilm formation by Pseudomonas putida was studied using suspended
      carriers in laboratory airlift reactors. Standard, roughened, hydrophobic, and
      positively charged glass beads, sand, and basalt grains were used as carriers.
      The results clearly show that in airlift reactors hydrodynamic conditions and
      particle collisions control biofilm formation. In the reactors, on surfaces
      subjected to different shear levels, biofilm formation differed considerably.
      This could be described by a simple growth and detachment model. Increased
      surface roughness promoted biofilm accumulation on suspended carriers. The
      physicochemical surface characteristics of the carrier surface proved to be less
      important due to the turbulent conditions in the airlift reactors. Adhesion of P.
      putida to glass beads was poor, and results of an adhesion test under quiescent
      conditions were not predictive for adhesion and subsequent biofilm formation
      under reactor conditions.

PMID- 18636599
TI  - A mathematical model of N-linked glycoform biosynthesis.
AB  - Metabolic engineering of N-linked oligosaccharide biosynthesis to produce novel
      glycoforms or glycoform distributions of a recombinant glycoprotein can
      potentially lead to an improved therapeutic performance of the glycoprotein
      product. Effective engineering of this pathway to maximize the fractions of
      beneficial glycoforms within the glycoform population of a target glycoprotein
      can be aided by a mathematical model of the N-linked glycosylation process. A
      mathematical model is presented here, whose main function is to calculate the
      expected qualitative trends in the N-linked oligosaccharide distribution
      resulting from changes in the levels of one or more enzymes involved in the
      network of enzyme-catalyzed reactions that accomplish N-linked oligosaccharide
      biosynthesis. It consists of mass balances for 33 different oligosaccharide
      species N-linked to a specified protein that is being transported through the
      different compartments of the Golgi complex. Values of the model parameters
      describing Chinese hamster ovary (CHO) cells were estimated from literature
      information. A basal set of kinetic parameters for the enzyme-catalyzed reactions
      acting on free oligosaccharide substrates was also obtained from the literature.
      The solution of the system for this basal set of parameters gave a glycoform
      distribution consisting mainly of complex-galactosylated oligosaccharides
      distributed in structures with different numbers of antennae in a fashion similar
      to that observed for various recombinant proteins produced in CHO cells. Other
      simulations indicate that changes in the oligosaccharide distribution could
      easily result from alteration in glycoprotein productivity within the range
      currently attainable in industry. The overexpression of N
      acetylglucosaminyltransferase III in CHO cells was simulated under different
      conditions to test the main function of the model. These simulations allow a
      comparison of different strategies, such as simultaneous overexpression of
      several enzymes or spatial relocation of enzymes, when trying to optimize a
      particular glycoform distribution.

PMID- 18636600
TI  - Comparison of Trichoplusia ni BTI-Tn-5B1-4 (high five) and Spodoptera frugiperda
      Sf-9 insect cell line metabolism in suspension cultures.
AB  - Nutrient utilization and byproduct accumulation were monitored in Spodoptera
      frugiperda Sf-9 and Trichoplusia ni BTI-Tn-5B1-4 (High Five) cell lines during
      growth and following viral infection in suspension cultures in order to develop a
      better understanding of cell metabolism and to acquire information relevant to
      large scale fed-batch bioreactors. The utilization of glucose, dissolved oxygen,
      and amino acids were monitored in Sf-9 cell cultures grown in Sf-900 II serum
      free medium (SFM) and in High Five cell cultures grown in both Sf-900 II and
      Express Five SFM. Using the optimal medium for each cell line, i.e., Sf-900 II
      SFM for Sf-9 cells and Express Five SFM for High Five cells, the cell growth
      rate, maximum cell density, specific glucose and glutamine utilization rates, and
      specific alanine production rate were comparable during cell growth. In addition,
      the expression level of recombinant human tissue plasminogen activator was
      comparable in the two cell lines on a per cell basis. It was found, however, that
      lactate and ammonia accumulated in High Five cell cultures, but not in Sf-9 cell
      cultures. In addition, High Five cells utilized asparagine more rapidly than
      glutamine, whereas Sf-9 cells consumed only minimal asparagine, and the oxygen
      utilization rate was significantly higher in High Five cell cultures. It was also
      found that the medium had a significant effect on High Five cell metabolism,
      e.g., the specific glucose utilization rate and the specific lactate and alanine
      production rates were significantly higher in Sf-900 II SFM than in Express Five
      SFM. In addition, the maximum cell density and specific asparagine utilization
      rate were significantly higher in Express Five SFM.

PMID- 18636601
TI  - On-line green fluorescent protein sensor with LED excitation.
AB  - We present an intensity based sensor designed for on-line monitoring of green
      fluorescent protein, a revolutionary marker of protein expression. The device
      consisted of a blue light emitting diode as the excitation source. A band pass
      excitation filter cut off light longer than 490 nm. The light was directed into a
      bifurcated optical fiber bundle with the common end inserted into a stainless
      steel housing equipped with a quartz window. The fiber bundle and stainless steel
      housing are steam sterilizable. The emission radiation was collected through a
      long wave pass filter to reject the excitation light shorter than 505 nm and was
      detected by a photomultiplier tube. The signal was amplified and sent to a
      computer for recording time course data. The sensor was tested in an Escherichia
      coli fermentation of JM105 transformed with pBAD-GFP. The on-line signal was
      compared to off-line fluorescence spectrophotometer measurements. The on-line
      profile closely followed the off-line. Western blot data showed that with a time
      shift, the sensor was able to both continuously and quantitatively monitor
      expression of green fluorescent protein on-line in real time.

PMID- 18636602
TI  - A novel cytostatic process enhances the productivity of Chinese hamster ovary
      cells.
AB  - We have established a novel production process which allows up to fourfold higher
      production of a model secreted protein, the human secreted alkaline phosphatase
      (SEAP), in Chinese hamster ovary (CHO) cells. A cytostatic production phase is
      established in which cell proliferation is inhibited or completely abolished.
      Such a cytostatic production phase is established by overexpression of the tumor
      suppressor genes p21, p27, or p53175P (a p53 mutant showing specific loss of
      apoptotic function) under transcriptional control of a tetracycline-repressible
      promoter (P(hCMV*-1)). In order to minimize complications due to possible clonal
      variation of selected, stable cell lines, our investigations are based on
      transiently transfected subpopulations, that have become a useful tool in
      industrial R&D. These subpopulations have been selected by flow cytometry for the
      expression of genes encoded on a dicistronic expression vector. These vectors
      contain a dicistronic expression unit consisting of the genes encoding the green
      fluorescent protein (GFP) or SEAP, followed by one of the cytostatic genes p21,
      p27 or p53175P encoded by the second cistron. p21, p27 as well as p53175P block
      the cell cycle of CHO cells in the G1-phase for a prolonged period. However,
      these G1-arrested cells remain viable and proliferation proficient upon
      repression of expression of the cytostatic gene. All three of the cytostatic
      genes studied provided similar regulation of proliferation, and also similar
      enhancements in SEAP production, suggesting that higher productivity may be a
      general and intrinsic feature of G1-phase arrested CHO cells. Overall
      productivity is most likely enhanced because growth-arrested cells do not need to
      devote cellular resources to biomass production.

PMID- 18636604
TI  - Kinetic studies of fusarium solani pisi cutinase used in a gas/solid system:
      transesterification and hydrolysis reactions.
AB  - Fusarium solani cutinase supported onto Chromosorb P was used to catalyze
      transesterification (alcoholysis) and hydrolysis on short volatile alcohols and
      esters in a continuous gas/solid bioreactor. In this system, a solid phase
      composed of a packed enzymatic preparation was continuously percolated with
      carrier gas which fed substrates and removed reaction products simultaneously. A
      kinetic study was performed under differential operating conditions in order to
      get initial reaction rates. The effect of the hydration state of the biocatalyst
      on the kinetics was studied for 3 conditions of hydration (a(w) = 0.2, a(w) = 0.4
      and a(w) = 0.6), the alcoholysis of propionic acid methyl ester with n-propanol,
      and for 5 hydration levels (from a(w) = 0.2 to a(w) = 0.6) for the hydrolysis of
      propionic acid methyl, ethyl or propyl esters. F. solani cutinase was found to
      have an unusual kinetic behavior. A sigmoid relationship between the rate of
      transesterification and the activity of methyl propionate was observed,
      suggesting some form of cooperative activation of the enzyme by one of its
      substrate. For the hydrolysis of short volatile propionic acid alkyl esters,
      threshold effects on the reaction rate, highly depending on the water activity
      and the substrate polarity, are reported.

PMID- 18636605
TI  - Kinetics and equilibria of condensation reactions between monosaccharide pairs
      catalyzed by Aspergillus niger glucoamylase.
AB  - Arabinose, fructose, galactose, myo-inositol, lyxose, mannose, ribose, and xylose
      were incubated individually and with glucose in the presence of Aspergillus niger
      glucoamylase at pH 4.5 and 45 degrees C. Glucoamylase condenses galactose,
      glucose, and mannose individually into disaccharides. It also produces mixed
      disaccharides when each of the eight carbohydrates is incubated with glucose.
      Many products were identified by gas chromatography of the derivatized reaction
      mixtures followed by mass spectroscopy of the individual chromatographic peaks.
      Galacto-, gluco-, or mannopyranosyl rings appear to be present at the nonreducing
      ends of all the disaccharides produced. Molecules linked through primary hydroxyl
      groups have the highest equilibrium constants of all products formed, since these
      bonds are thermodynamically favored. However, glucoamylase is capable of forming
      bonds with many available hydroxyl groups, as previously demonstrated when it was
      incubated with glucose alone. Formation rates of different bonds linking
      different residues vary widely. These results demonstrate that glucoamylase has a
      wide selectivity toward residues it will condense into disaccharides and toward
      bonds it will form between them.

PMID- 18636606
TI  - A novel feeding strategy for enhanced plasmid stability and protein production in
      recombinant yeast fedbatch fermentation.
AB  - A novel feeding strategy in fedbatch recombinant yeast fermentation was developed
      to achieve high plasmid stability and protein productivity for fermentation using
      low-cost rich (non-selective) media. In batch fermentations with a recombinant
      yeast, Saccharomyces cerevisiae, which carried the plasmid pSXR125 for the
      production of beta-galactosidase, it was found that the fraction of plasmid
      carrying cells decreased during the exponential growth phase but increased during
      the stationary phase. This fraction increase in the stationary phase was
      attributed to the death rate difference between the plasmid-free and plasmid
      carrying cells caused by glucose starvation in the stationary phase. Plasmid-free
      cells grew faster than plasmid-carrying cells when there were plenty of growth
      substrate, but they also lysed or died faster upon the depletion of the growth
      substrate. Thus, pulse additions of the growth substrate (glucose) at appropriate
      time intervals allowing for significant starvation period between two consecutive
      feedings during fedbatch fermentation should have positive effects on stabilizing
      plasmid and enhancing protein production. A selective medium was used to grow
      cells in the initial batch fermentation, which was then followed with pulse
      feeding of concentrated non-selective media in fedbatch fermentation. Both
      experimental data and model simulation show that the periodic glucose starvation
      feeding strategy can maintain a stable plasmid-carrying cell fraction and a
      stable specific productivity of the recombinant protein, even with a non
      selective medium feed for a long operation period. On the contrary, without
      glucose starvation, the fraction of plasmid-carrying cells and the specific
      productivity continue to drop during the fedbatch fermentation, which would
      greatly reduce the product yield and limit the duration that the fermentation can
      be effectively operated. The new feeding strategy would allow the economic use of
      a rich, non-selective medium in high cell density recombinant fedbatch
      fermentation. This new feeding strategy can be easily implemented with a simple
      IBM-PC based control system, which monitors either glucose or cell concentration
      in the fermentation broth.

PMID- 18636607
TI  - Substrate limitation in the baculovirus expression vector system.
AB  - The inability to infect insect cell cultures at the highest achievable cell
      densities has imposed major limitations to both the fundamental understanding of
      the Baculovirus Expression Vector System (BEVS) as well as full exploitation of
      its potential productive capacity for recombinant (beta-galAcNPV) products. The
      current literature does not characterize and identify the exact nature of the
      observed limitations, which therefore has become the major objective and
      contribution of the following study. Critical densities for infection of
      Spodoptera frugiperda (Sf9) cells with nuclear polyhedrosis virus expressing beta
      galactosidase (Autographa californica) grown in media both containing fetal calf
      serum (FCS) and free of serum were found to be at 2 x 10(6) and 5 x 10(6)
      cells/ml respectively. Medium exchange was found to completely reverse the effect
      if renewed up to 24 hours post-infection (HPI). The inevitable arrest of
      uninfected cell growth and decreased production of recombinant products at high
      cell densities of infection were both correlated to nutrient depletion. Cystine
      was found to be depleted in uninfected insect cell cultures at the onset of the
      stationary phase and in serum-free insect cell cultures infected with baculovirus
      above a cell density of 5 x 10(6) cells/ml. Neither glucose depletion nor
      accumulation of possible inhibitory metabolites such as alanine, ammonia, or
      lactate could be correlated to growth arrest or decreased recombinant product
      yields.

PMID- 18636608
TI  - One step purification of chymosin by mixed mode chromatography.
AB  - Mixed mode Sepharose and Perloza bead cellulose matrices were prepared using
      various chemistries. These matrices contained hydrophobic (aliphatic and/or
      aromatic) and ionic (carboxylate or alkylamine) groups. Hydrophobic amine ligands
      were attached to epichlorohydrin activated Sepharose (mixed mode amine matrices).
      Hexylamine, aminophenylpropanediol and phenylethylamine were the preferred
      ligands, on the basis of cost and performance. Other mixed mode matrices were
      produced by incomplete attachment (0-80%) of the same amine ligands to
      carboxylate matrices. The best results were obtained using unmodified or
      partially ligand-modified aminocaproic acid Sepharose and Perloza. High ligand
      densities were used, resulting in high capacity. Furthermore, chymosin was
      adsorbed at high and low ionic strengths, which reduced sample preparation
      requirements. Chymosin, essentially homogeneous by electrophoresis, was recovered
      by a small pH change. The methods described were simple, efficient, inexpensive
      and provided very good resolution of chymosin from a crude recombinant source.
      The carboxylate matrices had the best combination of capacity and regeneration
      properties. The performance of Sepharose and Perloza carboxylate matrices was
      similar, but higher capacities were found for the latter. Because it is cheaper
      and can be used at higher flow rates, Perloza should be better suited to large
      scale application. High capacity chymosin adsorption was found with carboxymethyl
      ion exchange matrices, but low ionic strength was essential for adsorption and
      the purity was inferior to that of the mixed mode matrices.

PMID- 18636609
TI  - Mapping of oxygen tension and cell distribution in a hollow-fiber bioreactor
      using magnetic resonance imaging.
AB  - We mapped the distribution of dissolved oxygen and mammalian cells in a hollow
      fiber bioreactor (HFBR) using (19)F NMR T(1) relaxation time imaging measurements
      on an infused perfluorocarbon probe molecule and diffusion-weighted (1)H NMR
      imaging of water. This study shows how cell density influences dissolved oxygen
      concentration in the reactor and demonstrates that NMR can play an important role
      in defining the biochemical engineering parameters required for optimization of
      HFBR design and operation.

PMID- 18636610
TI  - Determination of cells' water membrane permeability: unexpected high osmotic
      permeability of Saccharomyces cerevisiae.
AB  - Water permeability (Lp), calculated from the volume variations of cells subjected
      to an osmotic shock, is classically used to characterize cell membrane
      properties. In this work, we have shown the importance of the kind of mixing
      reactor used to measure the Lp parameter. A mathematical model including the
      mixing time constant has been proposed allowing an accurate Lp estimation even
      though the mixing time constant is higher than the cell time constant obtained in
      response to a perfect shock. The estimated Lp values of human leukemia K562 cells
      were found to be the same whatever the mixing time constant. The Lp value of
      Saccharomyces cerevisiae could not be exactly estimated. However, S. cerevisiae
      has unexpectedly high water permeability, implying that this yeast may contain
      water channels in the membrane.

PMID- 18636611
TI  - High performance tangential flow filtration.
AB  - Conventional tangential flow filtration (TFF) has traditionally been limited to
      separation of solutes that differ by about ten-fold in size. Wide pore-size
      distributions, membrane fouling, and concentration polarization phenomena have
      commonly been cited as reasons for this limitation. The use of TFF in the
      biotechnology industry has therefore been restricted to cell-protein, virus
      protein, and protein-buffer separations. A multi-disciplinary team with
      industrial and academic members was formed to overcome these limitations and
      enable protein-protein separations using High Performance TFF (HPTFF) systems.
      Pore-size distributions have been improved with the development of new membrane
      formulation and casting techniques. Membrane fouling has been controlled by
      operating in the transmembrane pressure-dependent regime of the filtrate flux
      curve and by carefully controlling fluid dynamic start-up conditions.
      Concentration polarization was exploited to enhance, rather than limit, the
      resolution of solutes. Concentration polarization has also been controlled by
      operating a co-current filtrate stream that maintains transmembrane pressure
      constant along the length of the TFF module. High yields and purification factors
      were obtained even with small differences in protein sieving. IgG-BSA and BSA
      monomer-oligomer mixtures have successfully been separated with these systems.
      HPTFF technology provides a competitive purification tool to complement
      chromatographic processing of proteins.

PMID- 18636612
TI  - Optimization and scale-up of solvent extraction in purification of hepatitis A
      virus (VAQTA).
AB  - Solvent extraction is a very powerful purification step in the preparation of
      VAQTA, a highly purified, inactivated hepatitis A vaccine. Extraction of an
      aqueous product-containing protein solution with chloroform through vigorous
      shaking causes irreversible denaturation of contaminant proteins at the
      interface. However, the hepatitis A virus (HAV) remains viable and soluble in the
      aqueous phase. Because three phases (air, aqueous, and organic) are involved, and
      the mixing is carried out in individual bottles, there is very little theory
      available to characterize this process, so it must be studied experimentally.
      This extraction step was characterized by following the removal of a specific
      impurity from the aqueous phase as a representative marker for the degree of
      protein precipitation. These experiments led to the identification and
      optimization of the important variables controlling the extraction step. They
      were found to be mixing time and size of vessel, with longer mixing times
      resulting in higher purity and larger bottle size leading to faster kinetics of
      impurity removal. These parameters are most likely related to solvent/aqueous
      interfacial area and the resulting shear due to shaking. We conclude that, to
      scale up this type of mixing, the kinetics of impurity removal need to be
      determined experimentally for the systems and equipment under consideration.

PMID- 18636613
TI  - Fouling of microfiltration membranes by broth-free antifoam agents.
AB  - The fouling tendencies of seven commercial antifoam agents used with
      microfiltration membranes were investigated in a stirred cell. Parameters such as
      viscosity, oil droplet size distribution, contact angle, work of adhesion (W(a)),
      membrane type, operating pressure, and feed concentration were examined. The
      results show that a silicone-based antifoam, G832, gave a significantly lower
      flux (<or=100 L h(-1) m(-2)) than the polypropylene glycol antifoam PPG2000 (1500
      2500 L h(-1) m(-2)) over the concentrations from 0.5 to 4.0 mL L(-1) at 50 kPa,
      700 rpm, and 25 degrees C. The significantly lower flux attained by the antifoam
      G832 was attributed to a number of factors, such as its greater viscosity (1.25 x
      10(-3) kg m(-1) s(-1) compared with 1.05 x 10(-3) kg m(-1) s(-1) for PPG2000), a
      smaller average oil droplet size (0.28 vs. 0.65 microm) comparable to the
      membrane pore size distribution (0.26-0.62 microm), a higher contact angle (98
      vs. 51 degrees ); and a significantly larger value of work of adhesion (26.0 vs.
      0.81 mN m(-1)). The different magnitudes of membrane adsorption by these antifoam
      agents, as reflected by their values of work of adhesion, were also observed in
      the field emission scanning electronic microscopy photographs. In terms of
      membrane type, the inorganic Anopore alumina membrane was found to offer a higher
      PPG flux than the organic Millipore polyvinyl difluoride (PVDF) membranes (both
      hydrophilic and hydrophobic). Furthermore, the mixed-type antifoams (B5600, B426,
      and G832) were found to give an increased hydraulic resistance and fouling
      percentage with an increase in pressure or feed concentration. Conversely for
      PPG2000, a reduction of the hydraulic resistance and fouling percentage was
      observed with increases of these two parameters.

PMID- 18636614
TI  - Experimental investigation and modeling of oscillatory behavior in the continuous
      culture of Zymomonas mobilis.
AB  - The mechanism causing oscillation in continuous ethanol fermentation by Zymomonas
      mobilis under certain operating conditions has been examined. A new term,
      "dynamic specific growth rate," which considers inhibitory culture conditions in
      the recent past affecting subsequent cell behavior, is proposed in this article.
      Based on this concept, a model was formulated to simulate the oscillatory
      behavior in continuous fermentation of Zymomonas mobilis. Forced oscillation
      fermentation experiments, in which exogenous ethanol was added at a controlled
      rate to generate oscillatory behavior, were performed in order to obtain
      estimates for the model parameters and to validate the proposed model. In
      addition, data from a literature example of a sustained oscillation were analyzed
      by means of the model, and excellent agreement between the model simulation and
      experimental results was obtained. The lag in the cells' response to a changing
      environment, i.e., ethanol concentration change rate experienced by the cells,
      was shown to be the major factor contributing to the oscillatory behavior in
      continuous fermentation of Zymomonas mobilis under certain operating conditions.

PMID- 18636615
TI  - Modeling assembly, aggregation, and chaperoning of immunoglobulin G production in
      insect cells.
AB  - A model for immunoglobulin G (IgG) production in the baculovirus-insect cell
      system was developed that incorporates polypeptide synthesis, oligomer assembly,
      protein aggregation, and protein secretion. In addition, the capacity of a
      chaperone to protect heavy and light chain polypeptides from protein aggregation
      was considered by including in vitro chaperone-peptide binding and dissociation
      kinetic constants from the literature. Model predictions were then compared to
      experiments in which the chaperone immunoglobulin heavy chain binding protein,
      BiP, was coexpressed by coinfecting insect cells with BiP-containing baculovirus.
      The model predicted a nearly twofold increase in intracellular and secreted IgG
      that was similar to the behavior observed experimentally after approximately 3
      days of coexpressing heterologous IgG and BiP. However, immunoglobulin
      aggregation was still significant in both the model simulation and experiments,
      so the model was then used to predict the effect of strategies for improving IgG
      production even further. Increasing expression of the chaperone BiP by 10-fold
      over current experimental levels provided a 2.5-fold increase in secreted IgG
      production over IgG assembly without BiP. Alternatively, the expression of BiP
      earlier in the baculovirus infection cycle achieved a twofold increase in protein
      secretion without requiring excessive BiP production. The potential effect of
      cochaperones on BiP activity was considered by varying the BiP binding and
      release constants. The utilization of lower binding and release kinetic constants
      led to a severalfold increase in IgG secretion because the polypeptides were
      protected from aggregation for greater periods. An optimized strategy for
      chaperone action would include the rapid peptide binding of a BiP-ATP
      conformation along with the slow peptide release of a BiP-ligand conformation.
      However, even with an optimized chaperoning system, limitations in the secretion
      kinetics can result in the accumulation of intracellular IgG. Thus, the entire
      secretory pathway must be considered when enhanced secretion of heterologous
      proteins is desired.

PMID- 18636616
TI  - Imaging of gynecological disease (4): clinical and ultrasound characteristics of
      struma ovarii.
AB  - OBJECTIVES: To describe the clinical history and ultrasound findings in women
      with struma ovarii. METHODS: Women with a histological diagnosis of struma ovarii
      who had undergone preoperative ultrasound examination were identified from the
      databases of five ultrasound centers. The tumors were characterized on the basis
      of ultrasound images, ultrasound reports and research protocols (when applicable)
      using the terms and definitions of the International Ovarian Tumor Analysis
      (IOTA) group. In addition, four authors reviewed all ultrasound images and
      described them using pattern recognition. RESULTS: Of 31 patients identified, 16
      had pure struma ovarii (one malignant), whereas in 15 patients the struma ovarii
      were 'impure', constituting the major part of a dermoid cyst (all benign,
      bilateral in one case). Median age was 40 (range, 18-80) years and 22 (71%)
      patients were of fertile age. Thirteen patients (42%) were asymptomatic, nine
      (29%) presented with pain, six (19%) with bloating, two (6%) with irregular
      bleeding and one (3%) with thyreotoxicosis. Most pure struma ovarii (11/16 cases,
      69%) contained solid components, but cystic components were always present. The
      color content at Doppler examination varied from none to abundant. Four patients
      had ascites. Using pattern recognition the most specific feature of pure struma
      ovarii was the 'struma pearl', i.e. a smooth roundish solid area, similar, but
      not identical, to the 'round white ball' seen in dermoid cysts. 'Struma pearls'
      were present in six cases of pure struma ovarii. Most (10/16, 63%) cases of
      impure struma ovarii manifested ultrasound features compatible with a dermoid
      cyst, but six manifested ultrasound features similar to those of pure struma
      ovarii, 'struma pearls' being seen in three of these. CONCLUSIONS: The
      sonographic features of struma ovarii vary. Struma ovarii may be suspected when a
      'struma pearl' is seen. Whether 'struma pearls' are indeed a specific
      ultrasonographic feature of struma ovarii needs to be determined in a prospective
      study.

PMID- 18636617
TI  - Selective displacement chromatography of proteins.
AB  - In contrast to high molecular weight polyelectrolyte displacers, the efficacy of
      low molecular weight displacers are dependent on both mobile phase salt and
      displacer concentration. This sensitivity to the operating conditions opens up
      the possibility of carrying out selective displacement where the product(s) of
      interest can be selectively displaced while the low affinity impurities can be
      desorbed in the induced salt gradient ahead of the displacement train, and the
      high affinity impurities either retained or desorbed in the displacer zone. This
      type of displacement combines the operational advantages of step gradient and the
      high resolution inherent in a true displacement process, in a single operation.
      Theoretical expressions are presented for establishing selective displacement
      operating conditions (initial salt concentration, displacer concentration) based
      on the Steric Mass Action parameters of the displacer and the linear Steric Mass
      Action parameters of the feed proteins. Experimental results are presented to
      elucidate the concept of selective displacement in both cation and anion exchange
      systems. A mixture of alpha-lactalbumin and beta-lactoglobulin A and B has been
      used for anion-exchange systems; a four-protein mixture consisting of
      ribonuclease B, bovine and horse heart cytochrome c, and lysozyme has been
      employed in cation exchange systems. This article also demonstrates that on-line
      monitoring can be readily employed for the selective displacement process, thus
      facilitating the scale-up and control of the process. This work sets the stage
      for the development of robust large scale high resolution separations using
      selective displacement chromatography. (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 56: 119-129, 1997.

PMID- 18636618
TI  - Continuous production of manganese peroxidase by Phanerochaete chrysosporium
      immobilized on polyurethane foam in a pulsed packed-bed bioreactor.
AB  - The bottleneck of the application of manganese peroxidase (MnP) on an industrial
      scale in pulp biobleaching or in degradation of hazardous compounds is the lack
      of an efficient production system. Three main problems arise for the continuous
      production of MnP during secondary metabolism of Phanerochaete chrysosporium:
      enzyme production occurs only under specific physiological conditions
      corresponding to C or N limitation, high O(2) tension, and adequate Mn(+2)
      concentration; the enzyme that is produced is destabilized by extracellular
      proteases; and excessive growth of the mycelium blocks effective oxygen transfer.
      To overcome these drawbacks, continuous production of MnP was optimized by
      selecting a suitable bioreactor configuration and the environmental and operating
      conditions affecting both enzyme production and stability. The combination
      between a proper feed rate and the application of a pulsation in a packed-bed
      bioreactor permitted the maintenance of continuous secretion of MnP while
      limiting mycelial growth and avoiding bed clogging. Environmental factors as an
      Mn(+2) concentration of 5000 microM and high oxygen tension enhanced MnP
      production. The hydraulics of the bioreactor corresponding to a plug flow model
      with partial mixing and an operating hydraulic rentention time of 24 h were
      optimal to achieve stable operating conditions. This policy allowed long
      operation periods, obtaining higher productivities than the best reported in the
      literature. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 130-137, 1997.

PMID- 18636619
TI  - Elevated Fis expression enhances recombinant protein production in Escherichia
      coli.
AB  - A genetic strategy to enhance recombinant protein production is discussed. A
      small DNA bending protein, Fis, which has been shown to activate rRNA synthesis
      upon a nutrient upshift, was overexpressed in E. coli strain W3110 carrying
      vector pUCR1. Overexpression of Fis during exponential growth was shown to
      activate rrn promoters to different extents. A 5-fold improvement in
      chloramphenicol acetyltransferase (CAT) production in cultures with elevated Fis
      level was observed in shake-flask cultivations. A similar improvement in the
      culture performance was also observed during fed-batch fermentation; the specific
      CAT activity increased by more than 50% during the fed-batch phase for cultures
      with elevated Fis expression. In contrast, no increase in specific CAT activity
      was detected for cultures carrying pUCR2, expressing a frame-shift Fis mutant.
      Expression of Fis from a complementary vector, pKFIS, restored CAT production
      from W3110:pUCR2 to approximately the same level as cultures carrying pUCR1,
      indicating that the enhancement in CAT production was indeed Fis-dependent. The
      framework presented here suggests that differential activation in recombinant
      protein production may be achieved with differential Fis overexpression. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 56: 138-144, 1997.

PMID- 18636620
TI  - Quantitative assessment of uncertainty in the optimization of metabolic pathways.
AB  - The S-System formalism provides a popular, versatile and mathematically tractable
      representation of metabolic pathways. At steady-state, after a logarithmic
      transformation, the S-System representation reduces into a system of linear
      equations. Thus, the maximization of a particular metabolite concentration or a
      flux subject to physiological constraints can be expressed as a linear
      programming (LP) problem which can be solved explicitly and exactly for the
      optimum enzyme activities. So far, the quantitative effect of
      parametric/experimental uncertainty on the S-model predictions has been largely
      ignored. In this work, for the first time, the systematic quantitative
      description of modeling/experimental uncertainty is attempted by utilizing
      probability density distributions to model the uncertainty in assigning a unique
      value to system parameters. This probabilistic description of uncertainty renders
      both objective and physiological constraints stochastic, demanding a
      probabilistic description for the optimization of metabolic pathways. Based on
      notions from chance-constrained programming and statistics, a novel approach is
      introduced for transforming the original stochastic formulation into a
      deterministic one which can be solved with existing optimization algorithms. The
      proposed framework is applied to two metabolic pathways characterized with
      experimental and modeling uncertainty in the kinetic orders. The computational
      results indicate the tractability of the method and the significant role that
      modeling and experimental uncertainty may play in the optimization of networks of
      metabolic reactions. While optimization results ignoring uncertainty sometimes
      violate physiological constraints and may fail to correctly assess objective
      targets, the proposed framework provides quantitative answers to questions
      regarding how likely it is to achieve a particular metabolic objective without
      exceeding a prespecified probability of violating the physiological constraints.
      Trade-off curves between metabolic objectives, probabilities of meeting these
      objectives, and chances of satisfying the physiological constraints, provide a
      concise and systematic way to guide enzyme activity alterations to meet an
      objective in the face of modeling and experimental uncertainty. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 56: 145-161, 1997.

PMID- 18636621
TI  - Integration of charged membrane into perstraction system for separation of amino
      acid derivatives.
AB  - The integration of a charged membrane into a perstraction system for high
      selective separation is reported. A mixture of N-(benzyloxycarbonyl)-L-aspartic
      acid (ZA), L-phenylalanine methyl ester (PM), and N-(benzyloxycarbonyl)-L
      aspartyl-L-phenylalanine methyl ester (ZAPM) was used as the model solution. The
      aqueous phase containing ZA, PM, and ZAPM was adjusted to pH 6 and was contacted
      with tert-amyl alcohol through a charged membrane. Seven different ion-exchange
      membranes and two different microfiltration membranes were tested for the
      separation system. Only ZAPM could permeate into the organic phase through
      SELEMION AMV and ASV. The separations between ZA and ZAPM and between PM and ZAPM
      were performed by biphasic extraction and electrostatic rejection, respectively.
      The permeabilities of ZAPM were higher than those of PM for all experiments using
      the ion-exchange membranes, although the molecular weight of ZAPM is larger than
      that of PM. The membrane that had a smaller pore size showed higher ZAPM
      selectivity. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 162-167,
      1997.

PMID- 18636622
TI  - Response of the central metabolism of Corynebacterium glutamicum to different
      flux burdens.
AB  - To evaluate the importance of reactions within the central metabolism under
      different flux burdens the fluxes within the pentose phosphate pathway (PPP), as
      well as the other reactions of the central metabolism, were intensively analyzed
      and quantitated. For this purpose, Corynebacterium glutamicum was grown with [1
      (13)C]glucose to metabolic and isotopic steady state and the fractional
      enrichments in precursor metabolites (e.g., pentose 5-phosphate) were quantified.
      Matrix calculus was used to express these data together with metabolite mass
      data. The detailed analysis of the dependence of (13)C enrichments on exchange
      fluxes enabled the transketolase-catalyzed exchange rate (2 pentose 5-phosphate <
      -> sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate) to be quantified as
      74.3% (molar metabolite flux) at a net flux of 10.3% and the exchange rate
      (pentose 5-phosphate + erythrose 4-phosphate <--> fructose 6-phosphate +
      glyceraldehyde 3-phosphate) to be quantified as 5.6% at a net flux of 8.1%. The
      flux entering the tricarboxylic acid cycle was 93.3%. The same comprehensive flux
      analysis as performed for the nonexcreting condition was done with the identical
      strain that had been forced to excrete L-glutamate. Because we had already
      quantified the fluxes for L-lysine excretion with an isogenic strain, three
      directly comparable flux situations are thus available. Consequently, this
      comparison permits a direct cause-and-effect relationship to be specified. In
      response to the different flux burdens of the cell, the PPP flux decreased from a
      maximum of 67% to 26%, with the glycolytic flux increasing accordingly. The
      carbon flux through isocitrate dehydrogenase increased from 20% to 36%. The
      bidirectional carbon flux between pyruvate and oxaloacetate decreased from 36% to
      9%. Since the cause of the three different flux states was the allelic exchange
      in the final L-lysine assembling pathway or the glutamate export activity,
      respectively, the flexible response is the effect. This shows conclusively the
      enormous flexibility within the central metabolism of C. glutamicum to supply
      precursors upon their withdrawal for the synthesis of amino acids. (c) 1997 John
      Wiley & Sons, Inc. Biotechnol Bioeng 56: 168-180, 1997.

PMID- 18636623
TI  - Properties of free and immobilized lipase from Pseudomonas cepacia.
AB  - The purified lipase from Pseudomonas cepacia (PS, Amano) was immobilized on a
      commercially available microporous polypropylene support. The enzyme was rapidly
      and completely adsorbed on the support. Special attention was devoted to the
      demonstration of the lack of diffusional limitations, either internal or
      external, when a soluble substrate (p-nitrophenylacetate, pNPA) was used. The
      activity yield was high (100%) with pNPA and very low (0.4%) with p
      nitrophenylpalmitate (pNPP). These values clearly showed that the immobilized
      enzyme was fully active as soon as activity was assayed on a soluble substrate
      rather than an insoluble one. With the latter one, the low activity was due
      mainly to a slow rate of substrate diffusion inside the porous support. The same
      diffusional phenomenon could explain the complete change of fatty acid
      specificity of the immobilized lipase. After immobilization, the lipase was
      mainly specific for short chain fatty acid esters, whereas the free enzyme was
      mainly specific for long chain esters. The activity-versus-temperature profiles
      were not greatly affected by immobilization with maximal reaction rates in the
      range 45 degrees to 50 degrees C for both enzyme preparations. However,
      immobilization increased enzyme stability mainly by decreasing the sensitivity to
      temperature of the inactivation reaction. Half-lives at 80 degrees C were 11 and
      4 min for the immobilized and free enzymes, respectively. (c) 1997 John Wiley &
      Sons, Inc. Biotechnol Bioeng 56: 181-189, 1997.

PMID- 18636624
TI  - Quantification of brewers' yeast flocculation in a stirred tank: effect of
      physical parameters on flocculation.
AB  - Quantification of yeast flocculation under defined conditions will help to
      understand the physical mechanisms of the flocculation process used in beer
      fermentation. Flocculation was quantified by measuring the size of yeast flocs
      and the number of single cells. For this purpose, a method to measure floc size
      and number of single cells in situ was developed. In this way, it was possible to
      quantify the actual flocculation during fermentation, without influencing
      flocculation. The effects of three physical parameters, floc strength, fluid
      shear, and yeast cell concentration, on flocculation during beer fermentation,
      were examined. Increasing floc strength results in larger flocs and lower numbers
      of single cells. If the fluid shear is increased, the size of the flocs
      decreases, and the number of single cells remains constant at approximately 10%
      of the total cells present. The cell concentration also influences flocculation,
      a reduction of 50% in cell concentration leads to a decrease of about 25% in floc
      size. The number of single cells decreases in linear proportion to the cell
      concentration. This means that, during yeast settling at full scale, the number
      of single cells decreases. The results of this study are used in a model for
      yeast flocculation. With respect to full scale fermentation the effect of cell
      concentration will play an important role, for flocculation and sedimentation
      will occur simultaneously leading to a quasi steady state between these
      phenomena. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 190-200, 1997.

PMID- 18636625
TI  - Evidence of bacterial adaptation to monochloramine in Pseudomonas aeruginosa
      biofilms and evaluation of biocide action model.
AB  - A mathematical model of biocide action against microbial biofilm was tested
      experimentally by measuring the response of Pseudomonas aeruginosa biofilm to
      various doses of monochloramine. Pure culture biofilm was developed in continuous
      flow annular reactors for 7 days, then treated with a 2-, 4-, or 8-h dose of 2 or
      4 mg L(-1) monochloramine. Some experiments investigated repeated treatment.
      Disinfection and regrowth of the biofilm were observed by sampling the biofilm
      for viable and total cell areal densities for up to 100 h following the biocide
      treatment. A phenomenological mathematical model was fitted to experimental data
      sets and captured overall trends, but it could not simulate certain
      experimentally observed features. The model did simulate rapid disinfection
      followed by steady regrowth. It correctly predicted a much greater decrease in
      viable than in total cell densities and also correctly captured the shapes of
      these trajectories. Discrepancies between the model and data included the
      following: the model predicted faster regrowth than was experimentally observed,
      the model predicted that a second dose would be more effective than the first
      dose but the opposite was observed in the experiments, and parameters estimated
      by fitting one dose concentration could not be used to predict the results of a
      different dose concentration or a second dose. Discrepancies between model and
      the experiment were hypothesized to be due to an adaptive stress response by the
      bacteria, a process not included in the model. A practical implication of this
      work is that it is more effective to deliver monochloramine in a short
      concentrated dose as opposed to a longer dose of lower concentration. (c) 1997
      John Wiley & Sons, Inc. Biotechnol Bioeng 56: 201-209, 1997.

PMID- 18636626
TI  - Modeling and optimization of a batch process for in vitro RNA production.
AB  - RNA molecules are commonly produced in vitro by transcription, utilizing a DNA
      template, an RNA polymerase enzyme, and nucleoside triphosphate substrates
      (NTPs). In addition to the full-length RNA molecule coded for by the DNA
      template, significant amounts of shorter RNA molecules are produced. A simplified
      model of this complex transcription process is presented, with the shorter RNA
      molecules lumped into a single pool. The rate equations do not depend on the
      stoichiometry of the RNA molecule of interest, which facilitates application of
      the model to other RNA molecules. Optimal initial conditions for batch in vitro
      RNA transcription to produce a dodecamer RNA containing three different
      nucleotides have been predicted using the model. The predicted optimal values for
      equimolar NTPs are 10 to 15 mM initial concentration for each NTP and 50 to 60 mM
      for magnesium acetate, yielding a maximum final dodecamer concentration of 0.8 +/
      0.1 mM at the 90% confidence interval. Experimental data agree well with the
      model results. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 210-220,
      1997.

PMID- 18636627
TI  - Performance characteristics of a reversible immunosensor with a
      heterobifunctional enzyme conjugate as signal generator.
AB  - Factors that control the performance of a reversible immunosensor with an analyte
      (progesterone)-enzyme (horseradish peroxidase) conjugate as signal generator have
      been investigated. The conjugate is used in conjunction with two antibodies,
      which are specific to progesterone and to horseradish peroxidase, immobilized on
      two spatially separated polypropylene mesh discs. The conjugate and two
      antibodies are confined to an internal compartment of a microdialyzer by a
      semipermeable membrane. The small analyte from an external medium permeates
      across the membrane into the internal compartment where the analyte concentration
      determines the relative amounts of the bound conjugate on the two solid surfaces.
      By measuring two signals from the conjugate bound at two separate sites, we
      experimentally obtained time-response curves to a concentration pulse of the
      external analyte. A mathematical (kinetic) model describing the sensor system was
      developed and used for the determination of rate-limiting factors. In
      semicontinuous monitoring of the analyte concentrations, operation of the
      immunosensor with the enzyme conjugate as signal generator required special
      attention to (a) enzyme stability, (b) analyte permeation (dependence on medium
      components), and (c) kinetics related to the different accessibility to the same
      antibody of the small analyte (to be measured) vs. the larger counterpart on the
      enzyme conjugate (for signal generation). (c) 1997 John Wiley & Sons, Inc.
      Biotechnol Bioeng 56: 221-231, 1997.

PMID- 18636628
TI  - Continuous operation of lipase-catalyzed reactions in nonaqueous solvents:
      Influence of the production of hydrophilic compounds.
AB  - In the field of biocatalysis in nonaqueous media, water has been identified as a
      crucial parameter which has to be carefully controlled. This article studies the
      continuous operation of a water-producing enzymatic reaction, here the
      esterification of oleic acid by ethanol in n-hexane catalyzed by Lipozyme(TM).
      The conversion decreased significantly over time, eventually coming to a lower
      steady-state level. This would be due to the accumulation of the produced water
      into the enzyme fixed-bed reactor, n-hexane being unable to evacuate this water
      out of the reaction vessel, because of the low polarity of this solvent.
      Therefore the conversion decreased until the produced water could be eliminated
      by the solvent achieving a steady state with a lower conversion. In supercritical
      carbon dioxide, a more hydrophilic solvent, steady state is at once obtained.
      This approach has been extended to reaction producing a hydrophilic compound,
      here glycerol during the transesterification between triolein and ethanol, and
      similar conclusions can be made. (c) 1997 John Wiley & Sons, Inc. Biotechnol
      Bioeng 56: 232-237, 1997.

PMID- 18636630
TI  - Introduction: advances in research on velo-cardio-facial syndrome/22q11.2
      deletion syndrome.

PMID- 18636631
TI  - Velo-cardio-facial syndrome: 30 Years of study.
AB  - Velo-cardio-facial syndrome is one of the names that has been attached to one of
      the most common multiple anomaly syndromes in humans. The labels DiGeorge
      sequence, 22q11 deletion syndrome, conotruncal anomalies face syndrome, CATCH 22,
      and Sedlackova syndrome have all been attached to the same disorder. Velo-cardio
      facial syndrome has an expansive phenotype with more than 180 clinical features
      described that involve essentially every organ and system. The syndrome has drawn
      considerable attention because a number of common psychiatric illnesses are
      phenotypic features including attention deficit disorder, schizophrenia, and
      bipolar disorder. The expression is highly variable with some individuals being
      essentially normal at the mildest end of the spectrum, and the most severe cases
      having life-threatening and life-impairing problems. The syndrome is caused by a
      microdeletion from chromosome 22 at the q11.2 band. Although the large majority
      of affected individuals have identical 3 megabase deletions, less than 10% of
      cases have smaller deletions of 1.5 or 2.0 megabases. The 3 megabase deletion
      encompasses a region containing 40 genes. The syndrome has a population
      prevalence of approximately 1:2,000 in the United States, although incidence is
      higher. Although initially a clinical diagnosis, today velo-cardio-facial
      syndrome can be diagnosed with extremely high accuracy by fluorescence in situ
      hybridization and several other laboratory techniques. Clinical management is age
      dependent with acute medical problems such as congenital heart disease, immune
      disorders, feeding problems, cleft palate, and developmental disorders occupying
      management in infancy and preschool years. Management shifts to cognitive,
      behavioral, and learning disorders during school years, and then to the potential
      for psychiatric disorders including psychosis in late adolescence and adult
      years. Although the majority of people with velo-cardio-facial syndrome do not
      develop psychosis, the risk for severe psychiatric illness is 25 times higher for
      people affected with velo-cardio-facial syndrome than that of the general
      population. Therefore, interest in understanding the nature of psychiatric
      illness in the syndrome remains strong.

PMID- 18636632
TI  - Molecular mechanisms and diagnosis of chromosome 22q11.2 rearrangements.
AB  - Several recurrent, constitutional genomic disorders are present on chromosome
      22q. These include the translocations and deletions associated with DiGeorge and
      velocardiofacial syndrome and the translocations that give rise to the recurrent
      t(11;22) supernumerary der(22) syndrome (Emanuel syndrome). The rearrangement
      breakpoints on 22q cluster around the chromosome-specific segmental duplications
      of proximal 22q11, which are involved in the etiology of these disorders. While
      the deletions are the result of nonallelic homologous recombination (NAHR)
      between low copy repeats or segmental duplications within 22q11, the t(11;22) is
      the result of rearrangement between palindromic AT-rich repeats on 11q and 22q.
      Here we describe the mechanisms responsible for these recurrent rearrangements,
      discuss the recurrent deletion endpoints that are the result of NAHR between
      chromosome 22q specific low copy repeats as well as present current diagnostic
      approaches to deletion detection.

PMID- 18636633
TI  - Genetic modifiers of the physical malformations in velo-cardio-facial
      syndrome/DiGeorge syndrome.
AB  - Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro
      deletion disorder in humans, is characterized by craniofacial, parathyroid, and
      thymic defects as well as cardiac outflow tract malformations. Most patients have
      a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse
      have shown that Tbx1, a T-box containing transcription factor present on the
      deleted region, is likely responsible for the etiology of the syndrome.
      Furthermore, mutations in TBX1 have been found in rare non-deleted patients.
      Despite having the same sized deletion, most VCFS/DGS patients exhibit
      significant clinical variability. Stochastic, environmental and genetic factors
      likely modify the phenotype of patients with the disorder. Here, we review mouse
      genetics studies, which may help identify possible genetic modifiers for the
      physical malformations in VCFS/DGS.

PMID- 18636634
TI  - Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome.
AB  - There is an overwhelming evidence that children and adults with 22q11.2 deletion
      syndrome (22q11.2DS) have a characteristic behavioral phenotype. In particular,
      there is a growing body of evidence that indicates an unequivocal association
      between 22q11.2DS and schizophrenia, especially in adulthood. Deletion of 22q11.2
      is the third highest risk for the development of schizophrenia, with only a
      greater risk conferred by being the child of two parents with schizophrenia or
      the monozygotic co-twin of an affected individual. Both linkage and association
      studies of people with schizophrenia have implicated several susceptibility
      genes, of which three are in the 22q11.2 region; catechol-o-methyltransferase
      (COMT), proline dehydrogenase (PRODH), and Gnb1L. In addition, variation in Gnb1L
      is associated with the presence of psychosis in males with 22q11.2DS. In mouse
      models of 22q11.2DS, haploinsufficiency of Tbx1 and Gnb1L is associated with
      reduced prepulse inhibition, a schizophrenia endophenotype. The study of
      22q11.2DS provides an attractive model to increase our understanding of the
      development and pathogenesis of schizophrenia and other psychiatric disorders in
      22q11.2DS and in wider population.

PMID- 18636635
TI  - Cardiac defects and results of cardiac surgery in 22q11.2 deletion syndrome.
AB  - Specific types and subtypes of cardiac defects have been described in children
      with 22q11.2 deletion syndrome as well as in other genetic syndromes. The
      conotruncal heart defects occurring in patients with 22q11.2 deletion syndrome
      include tetralogy of Fallot, pulmonary atresia with ventricular septal defect,
      truncus arteriosus, interrupted aortic arch, isolated anomalies of the aortic
      arch, and ventricular septal defect. These conotruncal heart defects are
      frequently associated in this syndrome with additional cardiovascular anomalies
      of the aortic arch, pulmonary arteries, infundibular septum, and semilunar valves
      complicating cardiac anatomy and surgical treatment. In this review we describe
      the surgical anatomy, the operative treatment, and the prognostic results of the
      cardiac defects associated with 22q11.2 deletion syndrome. According to the
      current literature, in patients with tetralogy of Fallot with/without pulmonary
      atresia and truncus arteriosus, in spite of the complex cardiac anatomy, the
      presence of 22q11.2 deletion syndrome does not worsen the surgical prognosis. On
      the contrary in children with pulmonary atresia with ventricular septal defect
      and probably in those with interrupted aortic arch the association with 22q11.2
      deletion syndrome is probably a risk factor for the operative treatment. The
      complex cardiovascular anatomy in association with depressed immunological
      status, pulmonary vascular reactivity, neonatal hypocalcemia, bronchomalacia and
      broncospasm, laryngeal web, and tendency to airway bleeding must be considered at
      the time of diagnosis and surgical procedure. Specific diagnostic, surgical, and
      perioperative protocols should be applied in order to provide appropriate
      treatment and to reduce surgical mortality and morbidity.

PMID- 18636636
TI  - The neurocognitive phenotype in velo-cardio-facial syndrome: a developmental
      perspective.
AB  - Although research has focused primarily on the wide range of variability in the
      cognitive phenotype between individuals with velo-cardio-facial syndrome (VCFS),
      we know relatively little about the extent to which within-individual expressions
      of the cognitive phenotype remain stable throughout development. General
      cognitive functioning in the low borderline range is the most consistent
      cognitive finding. Stronger reading decoding and spelling skills as well as
      auditory/verbal rote memory skills have been reported to be areas of relative
      strength. Conversely, significant visuospatial dysfunction, diminished math
      attainment, and executive dysfunction have all been reported as phenotypic. We
      propose several considerations that could advance our knowledge of developmental
      changes in the VCFS cognitive phenotype. The most salient of these is the need
      for more longitudinal designs with carefully matched control participants.

PMID- 18636638
TI  - Genetic counseling for the 22q11.2 deletion.
AB  - Because of advances in palliative medical care, children with the 22q11.2
      deletion syndrome are surviving into adulthood. An increase in reproductive
      fitness will likely follow necessitating enhanced access to genetic counseling
      for these patients and their families. Primary care physicians/obstetric
      practitioners are in a unique position to identify previously undiagnosed
      patients as they reach reproductive age and to refer them for genetic counseling.
      To date, most deletions are de novo, secondary to homologous recombination
      between low-copy repeat sequences located within 22q11.2. Nonetheless, both
      somatic and germ line mosaicism has been observed giving unaffected parents a
      small risk of recurrence. Once present though there is a 50% chance for a person
      with this contiguous deletion to have an affected child. With this in mind, a
      variety of prenatal monitoring techniques, as well as, preimplantation genetic
      diagnosis are available depending on the specific level of risk.

PMID- 18636637
TI  - Genes, brain development and psychiatric phenotypes in velo-cardio-facial
      syndrome.
AB  - Velo-cardio-facial syndrome (VCFS) has been in the focus of intensive research
      over the last 15 years. The syndrome represents a homogeneous model for studying
      the effect of a decreased dosage of genes on the development of brain structure
      and function and, consequently, on the emergence of schizophrenia-like psychotic
      disorder. In this review, we describe the psychiatric phenotype of children,
      adolescents, and young adults with VCFS. We redefine the concept of "behavioral
      phenotype" and suggest that psychosis fulfills the criteria of a behavioral
      phenotype of the syndrome. Identifying the risk factors for the emergence of
      psychosis in VCFS is a major goal of several large-scale longitudinal studies
      that are currently underway. We review the knowledge gained so far about risk
      factors for psychosis in VCFS, including early neuropsychiatric symptoms,
      development of brain structure and function, and the effect of a reduced dosage
      of genes from the 22q11 deletion region. Although the brain structure in subjects
      with VCFS is not drastically different from typically developing controls, newer
      imaging modalities that measure white matter tracts, cortical thickness, and
      cortical gyrification are likely to identify more subtle and specific
      neuroanatomical substrates of the syndrome. Among the 24 genes within the
      deletion region, the role of catechol-O-methyltransferase (COMT) on the VCFS
      phenotype has been investigated in depth. The findings suggest that because of
      haploinsufficiency of the COMT gene individuals with VCFS are exposed to a high
      level of prefrontal dopamine, and this interferes with their prefrontal cognitive
      functioning and may contribute to their high rate of psychosis and other
      psychiatric disorders. The other genes and environmental factors that shape the
      unique neuropsychiatric phenotype of VCFS are yet to be discovered.

PMID- 18636639
TI  - Expression of green fluorescent protein in insect larvae and its application for
      heterologous protein production.
AB  - Many eukaryotic proteins have been successfully expressed in insect cells
      infected with a recombinant baculovirus derived from the Autographa californica
      nuclear polyhedrosis virus (AcNPV). There are, however, disadvantages with this
      cell-based system when carried out in suspension cultures at high bioreactor
      volume (e.g., limited oxygen transfer, susceptibility to contamination, high
      cost). These problems can be avoided by using whole larvae as the "reactors."
      There are, however, other problems encountered with larvae, one being their
      inaccessibility for product sampling. To combat this problem, we have
      investigated the expression of green fluorescent protein (GFP) as a reporter
      molecule in Trichoplusia ni insect larvae. A high production level of GFPuv (1.58
      mg per larva, 26% of total protein) was obtained, enabling the rapid and non
      invasive monitoring of GFP. Bright green light was emitted directly from the
      large opaque carcasses ( approximately 30mm) after illumination with UV light.
      Based on the green light intensity and a correlation between intensity and GFP
      mass, we determined the optimal harvest time (c.a. approximately 3 days post
      infection). In parallel experiments, we expressed human interleukin-2 (IL-2) from
      another recombinant baculovirus with an almost identical expression profile.
      Since both GFP and IL-2 were rapidly degraded by protease activity during the
      fourth day post-infection (another disadvantage with larvae), we found an
      accurate determination of harvest time was critical. Correspondingly, our results
      demonstrated that GFP was an effective on-line marker for expression of
      heterologous protein in insect larvae.

PMID- 18636640
TI  - Predicting the partition coefficients of a recombinant cutinase in polyethylene
      glycol/phosphate aqueous two-phase systems.
AB  - A model for the prediction of protein partition coefficients in aqueous two-phase
      systems has been developed. This model accounts for both charge-independent and
      electrostatic effects. The determination of nonelectrostatic effects was based on
      the model of Eiteman and Gainer for uncharged solutes while the electrostatic
      contribution was computed using TITRA, a program that uses a continuum
      electrostatic model to treat charge interactions in proteins and considers the
      effect of pH and ionic strength. The partition coefficients of Fusarium solani
      pisi recombinant cutinase have been satisfactorily predicted in polyethylene
      glycol (PEG) 1000 and phosphate aqueous two-phase systems at a pH range of 6.0
      9.0. The model failed to predict the enzyme partitioning behavior at pH 4.5.

PMID- 18636641
TI  - Biological breakdown of RDX in slurry reactors proceeds with multiple kinetically
      distinguishable paths.
AB  - Biotransformation of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) in slurry
      reactors was studied to determine the importance of supplementation of known
      biodegraders and the type of nutrient source required. Although addition of
      bacteria to the system increased the biotransformation rates, the increase may
      not justify the additional work and cost needed to grow the organisms in a
      laboratory and mix them into the soil. An inexpensive, rich nutrient source, corn
      steep liquor, was shown to provide sufficient nutrients to allow for the
      cometabolic biotransformation of RDX. The rate of RDX transformation was not
      constant throughout the course of the experiment due to the heterogeneous
      microbial population. Three kinetically distinct phases were observed. Regardless
      of the process, RDX biotransformation in slurry reactors was reaction rate
      limited under the test conditions. Model simulations based on experimental
      results demonstrate that, at cell densities of 5 g/L, bioremediation of RDX
      contaminated soil is an attractive clean-up alternative.

PMID- 18636642
TI  - Hydrogen transfer between methanogens and fermentative heterotrophs in
      hyperthermophilic cocultures.
AB  - Interactions involving hydrogen transfer were studied in a coculture of two
      hyperthermophilic microorganisms: Thermotoga maritima, an anaerobic heterotroph,
      and Methanococcus jannaschii, a hydrogenotrophic methanogen. Cell densities of T.
      maritima increased 10-fold when cocultured with M. jannaschii at 85 degrees C,
      and the methanogen was able to grow in the absence of externally supplied H(2)
      and CO(2). The coculture could not be established if the two organisms were
      physically separated by a dialysis membrane, suggesting the importance of spatial
      proximity. The significance of spatial proximity was also supported by cell
      cytometry, where the methanogen was only found in cell sorts at or above 4.5
      microm in samples of the coculture in exponential phase. An unstructured
      mathematical model was used to compare the influence of hydrogen transport and
      metabolic properties on mesophilic and hyperthermophilic cocultures. Calculations
      suggest the increases in methanogenesis rates with temperature result from
      greater interactions between the methanogenic and fermentative organisms, as
      evidenced by the sharp decline in H(2) concentration in the proximity of a
      hyperthermophilic methanogen. The experimental and modeling results presented
      here illustrate the need to consider the interactions within hyperthermophilic
      consortia when choosing isolation strategies and evaluating biotransformations at
      elevated temperatures.

PMID- 18636643
TI  - On-line monitoring and control of methanol concentration in shake-flask cultures
      of Pichia pastoris.
AB  - The methylotrophic yeast Pichia pastoris can be used to express recombinant genes
      at high levels under the control of the methanol-inducible alcohol oxidase 1
      (AOX1) promoter. Accurate regulation of the methanol concentration in P. pastoris
      cultures is necessary to maintain induction, while preventing accumulation of
      methanol to cytotoxic levels. We developed an inexpensive methanol sensor that
      uses a gas-permeable silicone rubber tube immersed in the culture medium and an
      organic solvent vapor detector. The sensor was used to monitor methanol
      concentration continuously throughout a fed-batch shake-flask culture of a P.
      pastoris clone producing the N-lobe of human transferrin. The sensor calibration
      was stable for the duration of the culture and the output signal accurately
      reflected the methanol concentration determined off-line by HPLC. A closed-loop
      control system utilizing this sensor was developed and used to maintain a 0.3%
      (v/v) methanol concentration in the culture. Use of this system resulted in a
      fivefold increase in volumetric protein productivity over levels obtained using
      the conventional fed-batch protocol.

PMID- 18636644
TI  - Morphometric evaluation of the specific growth rate of Aspergillus niger grown in
      agar plates at high glucose levels.
AB  - Development of surface grown cultures of Aspergillus niger no. 10 was studied at
      two experimental levels: (a) following the time course of the biomass density (X
      [=] mg cm(-2)) and fitting the data by the logistic expression, which yielded a
      macroscopic specific growth rate expressed as micro(obs) = (dX/Xdt)[1
      (X/X(max))](-1); and (b) measuring morphometric parameters like the specific
      elongation rate (k) of the germ tubes and their diameters (D(h)), the colony rate
      of radial extension (u(r)), and the mean length of distal hyphae (L(av)) to
      estimate the specific growth rate with the following proposed expression:
      micro(calc) = u(r)ln2[L(av)ln(L(av)/D(h))](-1). Increases in the initial glucose
      concentration (10, 40, 70, 120, 200, and 300 g L(-1)) caused reductions in the
      specific growth rates, the elongation kinetics of the germ tubes, and the hyphal
      diameter, nevertheless, u(r) and X(max) presented parabolic behavior, showing
      their maxima in the interval of 90 to 120 g L(-1) of glucose. The overall
      macroscopic effect of the tested concentrations of glucose on surface grown
      cultures of A. niger was to produce densely packed and slowly extending colonies,
      where changes in hyphal lengths and diameters were significant. There was good
      agreement between micro(obs) and micro(calc) values. Hence, this work validates a
      kinetic model based on morphometric data to estimate the specific growth rate of
      molds, obtained from dry weight data, using mold cultures grown in the same solid
      medium i.e., agar plates.

PMID- 18636645
TI  - Performance of three phase fluidized bed reactor for quinoline degradation on
      various supports at steady state and dynamic conditions.
AB  - Quinoline degradation by Comamonas acidovorans was investigated in a three phase
      fluidized bed reactor at dilution rates below and above the critical value
      (micro(max) = 0.42 h(-1)). Quinoline was used as the sole source of carbon,
      nitrogen, and energy. Two attachment carriers, polyurethane foam (Bayvitec) and
      modified cellulose (Aquacel), and a gel entrapment carrier (polyvinyl alcohol)
      were studied and compared with regard to their effectiveness to immobilize cells.
      Attachment and biofilm formation was best at higher dilution rates, regardless of
      carrier type used. Except for the maximum biomass concentration on the carrier,
      Y(V) (biomass per volume of solid particles), there was no significant difference
      in reactor performance between the investigated carriers under stationary
      conditions. The highest value for Y(V) was found for the gel entrapment carrier
      (Y(V) = 35 g L(-1)). In a long-term run (66 days), the gel entrapment carrier
      established a permanent biofilm on the surface of the gel beads after 900 h of
      cultivation time. Complete quinoline mineralization was achieved at a dilution
      rate of 2.0 h(-1), which is 4.7 times higher than the critical dilution rate.
      Identical substrate overloads were applied to the gel entrapment and the
      cellulose carrier by a step increase of the quinoline feed concentration at a
      dilution rate of 0.8 h(-1) (D approximately 2micro(max)). The cells survived the
      overload, but the accumulation of quinoline and quinoline degradation products
      and the degradation efficiency were different for the two systems during the
      overload, showing the influence of the carrier type on the dynamic performance
      and stability of the process.

PMID- 18636646
TI  - Crossflow microfiltration of recombinant Escherichia coli lysates after high
      pressure homogenization.
AB  - Crossflow membrane filtration was used to process recombinant Escherichia coli
      cell lysates containing protein inclusion bodies after high pressure
      homogenization. The number of passes through the high pressure homogenizer
      changed the viscosities and average particle sizes of the cell lysates. The
      different cell lysates were processed with a hollow fiber unit containing
      microfiltration membranes and a plate and frame unit with either ultrafiltration
      or microfiltration membranes. There were differences in permeate flux and protein
      transmission for the various membranes with the best performing membranes giving
      permeate fluxes greater than 60 L m(-2) h(-1) and protein transmissions greater
      than 90%. For a given membrane, no differences were observed between the cell
      lysates following homogenization with one, two, and three passes at 83 MPa. The
      lack of a difference between the three lysates is due to their similarities with
      respect to the released macromolecules and the presence of small (<0.1 microm)
      cell debris.

PMID- 18636647
TI  - Polymer-induced phase separation in aqueous micellar solutions of octyl-beta-D
      thioglucoside for extraction of membrane proteins.
AB  - A water-soluble polymer such as polyethylene glycol (PEG), Dextran T-500 (Dx), or
      diethylaminoethyl-Dextran (DEAE-Dx) induced aqueous micellar solutions of octyl
      beta-D-thioglucoside (OTG) to phase separation at 0 degrees C. One of the two
      phases thus formed is a surfactant-depleted aqueous solution (aqueous phase) of a
      water-soluble polymer and the other a concentrated OTG solution (surfactant-rich
      phase). In a combination of OTG with PEG or Dx, cytochrome P450 (P450) and
      cytochrome b(5) (b(5)) were well extracted into the surfactant-rich phase. The
      extraction yield of P450 was slightly greater than that of b(5). In contrast to
      PEG and Dx, DEAE-Dx markedly reduced the extraction of b(5), while that of P450
      remained almost unchanged. DEAE-Dx served the dual functions of inducing the
      phase separation and preventing the extraction of b(5) into the surfactant-rich
      phase. This depressed extraction of b(5) was reversed by the addition of
      potassium phosphate. DEAE-Dx and potassium phosphate proved effective in
      controlling the extractability of b(5). The polymer-induced phase separation
      provides a new basis for highly efficient extraction of membrane proteins under
      mild conditions that should be acceptable for thermolabile membrane proteins
      under physiological conditions.

PMID- 18636648
TI  - Prediction of average biofilm density and performance of a spherical bioparticle
      under substrate inhibition.
AB  - In this article, a model was proposed to predict the average performance and
      biofilm density of a spherical bioparticle under substrate inhibition in a
      fluidized bed system. The average biofilm density and substrate consumption rates
      were predicted for a definite biofilm thickness and limiting substrate
      concentrations. A diffusion and reaction model was developed over the bioparticle
      with biofilm-density dependent effective diffusion coefficients for maximum
      substrate consumption theory. This theory predicts the optimum density of a
      biofilm to yield a maximum substrate consumption rate within the biofilm,
      developed for the first time with this study and experimentally verified. A good
      correlation was observed between the model prediction and experimental results
      for biofilm density and substrate consumption rates.

PMID- 18636649
TI  - Shift from growth to nutrient-limited maintenance kinetics during biofilter
      acclimation.
AB  - During long-term operation of a biofilter, the mandatory absence of net cell
      growth forces the cells into maintenance metabolism, which is of relatively low
      rate compared to substrate consumption during the active growth of the
      acclimation phase. A model based on this shift in metabolism can explain the
      postacclimation decrease in activity sometimes reported for biofilters. The
      cessation of growth can be caused by nutrient depletion in the bed.
      Postacclimation nutrient addition increases activity primarily by allowing a
      return to the high substrate consumption rate of active growth, and only
      secondarily helps raise bed activity because of the ultimately higher amount of
      biomass in the bed. Simulations incorporating the acclimation period and the role
      of maintenance metabolism predict about 4 logarithms of growth during acclimation
      of a hexane biofilter, which was confirmed experimentally. Changes in a
      biofilter's biomass during the acclimation phase can be estimated from substrate
      conversion data using two approximate methods. The first follows the cumulative
      amount of substrate converted and uses the estimated yield of cells from
      substrate during active growth to estimate the total biomass created. The second
      method follows a rate constant for conversion of substrate in the bed.

PMID- 18636650
TI  - Thermodynamic analysis of solvent effect on substrate specificity of lyophilized
      enzymes suspended in organic media.
AB  - A simple methodology has been successfully employed to explain the solvent
      dependence of the substrate specificity of enzymes in organic media. This
      methodology, which does not require the knowledge of the enzyme structure and is
      thus applicable to lyophilized and other noncrystalline enzyme preparations,
      predicts that the k(cat)/K(M) ratio for two substrates should be proportional to
      their Raoult's law activity coefficients. This approach has been validated for
      two enzymes, subtilisin Carlsberg and alpha-chymotrypsin, catalyzing the
      propanolysis of unnatural (in addition to natural) ester substrates in a variety
      of anhydrous solvents.

PMID- 18636651
TI  - Boron based separations for in situ recovery of L-erythrulose from transketolase
      catalyzed condensation.
AB  - In this article we report on the application of in situ product removal (ISPR)
      (the concurrent recovery of a product during the product formation process) as a
      means of improving the productivity of bioconversions. The Escherichia coli
      transketolase-catalyzed condensation of glycolaldehyde with beta-hydroxypyruvate
      to yield L-erythrulose (and carbon dioxide) was chosen as a model system. Those
      ISPR methods based on phenylboronate-diol interactions showed greatest potential
      for use as a selective means of removing L-erythrulose from the reaction medium.
      Soluble, insoluble, and immobilized boronates were investigated. Concentrations
      of free phenylboric acid of 100 mM and above were toxic to transketolase, thus
      rendering the use of these methods unsuitable for ISPR. However, one of the
      immobilized phenylboronate resins (Affi-Gel 601) was not toxic to the enzyme,
      although significant levels of nonspecific binding of both substrates were
      observed. When ISPR was performed on the model reaction using this resin with
      substrate feeding, it proceeded to completion.

PMID- 18636652
TI  - Mechanisms of heme iron absorption: current questions and controversies.
AB  - Iron is a critical micronutrient, and iron derived from heme contributes a large
      proportion of the total iron absorbed in a typical Western diet. Heme iron is
      absorbed by different mechanisms than non-heme iron, but despite considerable
      study over many years these mechanisms remain poorly understood. This review
      provides an overview of the importance of heme iron in the diet and discusses the
      two prevailing hypotheses of heme absorption; namely receptor mediated
      endocytosis of heme, and direct transport into the intestinal enterocyte by
      recently discovered heme transporters. A specific emphasis is placed on the
      questions surrounding the site of heme catabolism and the identity of the enzyme
      that performs this task. Additionally, we present the hypothesis that a non-heme
      iron transport protein may be required for heme iron absorption and discuss the
      experiences of our laboratory in examining this hypothesis.

PMID- 18636653
TI  - Liver in systemic disease.
AB  - Potential causes of abnormal liver function tests include viral hepatitis,
      alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases,
      hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug
      induced liver injury. Moreover, the liver may be involved in systemic diseases
      that mainly affect other organs. Therefore, in patients without etiology of liver
      injury by screening serology and diagnostic imaging, but who have systemic
      diseases, the abnormal liver function test results might be caused by the
      systemic disease. In most of these patients, the systemic disease should be
      treated primarily. However, some patients with systemic disease and severe liver
      injury or fulminant hepatic failure require intensive treatments of the liver.

PMID- 18636654
TI  - Hepatic steatosis: a benign disease or a silent killer.
AB  - Steatosis is a common feature of many liver diseases, namely non-alcoholic
      steatohepatitis (NASH) and hepatitis C virus (HCV) infection, but the pathogenic
      mechanisms differ. Insulin resistance (IR), a key feature of metabolic syndrome,
      is crucial for NASH development, associated with many underlying genetically
      determined or acquired mitochondrial and metabolic defects and culminates to
      inflammation and progression to fibrosis. This may have potential implications
      for new drug therapy. In HCV-related disease, steatosis impacts both fibrosis
      progression and response to treatment. Steatosis in HCV-related disease relates
      to both viral factors (HCV genotype 3), and host factors (alcohol consumption,
      overweight, hyperlipidemia, diabetes). Among others, IR is a recognized factor.
      Hepatic steatosis is reported to be associated with disturbance in the signaling
      cascade of interferon and downregulation of its receptors. Thus, hepatic
      steatosis should not be considered a benign feature, but rather a silent killer.

PMID- 18636655
TI  - Use of the Crohn's disease activity index in clinical trials of biological
      agents.
AB  - The Crohn's disease activity index (CDAI) has been commonly used to assess the
      effects of treatment with different agents in Crohn's disease (CD). However,
      these studies may be compromised, if the results compared to a placebo or
      standard therapy group (in the absence of a placebo) substantially differ from
      the expected response. In addition, significant concerns have been raised
      regarding the reliability and validity of the CDAI. Reproducibility of the CDAI
      may be limited as significant inter-observer error has been recorded, even if
      measurements are done by experienced clinicians with expertise in the diagnosis
      and treatment of CD. Finally, many CDAI endpoints are open to subjective
      interpretation and have the potential for manipulation. This is worrisome as
      there is the potential for significant financial gain, if the results of a
      clinical trial appear to provide a positive result. Physicians caring for
      patients should be concerned about the positive results in clinical trials that
      are sponsored by industry, even if the trials involve respected centers and the
      results appear in highly ranked medical journals.

PMID- 18636656
TI  - Diagnostic approaches for cholangiocarcinoma.
AB  - Cholangiocarcinomas arise from the epithelial cells of the bile ducts and are
      associated with poor prognosis. Despite new diagnostic approaches, the definite
      diagnosis of this malignancy continues to be challenging. Cholangiocarcinomas
      often grow longitudinally along the bile duct rather than in a radial direction.
      Thus, large tumor masses are frequently absent and imaging techniques, including
      ultrasound, CT, and MRI have only limited sensitivity. Tissue collection during
      endoscopic (ERCP) and/or percutaneous transhepatic (PTC) procedures are usually
      used to confirm a definitive diagnosis of cholangiocarcinoma. However, forceps
      biopsy and brush cytology provide positive results for malignancy in about only
      50% of patients. Percutaneous and peroral cholangioscopy using fiber-optic
      techniques were therefore developed for direct visualization of the biliary tree,
      yielding additional information about endoscopic appearance and tumor extension,
      as well as a guided biopsy acquistion. Finally, endoscopic ultrasonography (EUS)
      complements endoscopic and percutaneous approaches and may provide a tissue
      diagnosis of tumors in the biliary region through fine-needle aspiration. In the
      future, new techniques allowing for early detection, including molecular markers,
      should be developed to improve the diagnostic sensitivity in this increasing
      tumor entity.

PMID- 18636657
TI  - Expanding role of capsule endoscopy in inflammatory bowel disease.
AB  - Capsule endoscopy has been shown to detect small bowel inflammatory changes
      better than any other imaging modality. Selection criteria have been optimized to
      increase the yield of capsule endoscopy in patients suspected to have Crohn's
      disease. Capsule endoscopy allows for earlier diagnosis of Crohn's disease of the
      small bowel and improved diagnosis of colitis in patients where it is unclear if
      they suffer from Crohn's or ulcerative colitis. A test capsule is available to
      assess for small bowel strictures and thus avoid capsule retention. A common
      language has been developed and a new scoring index will be added to capsule
      software. It is envisioned that the manner in which we treat Crohn's disease in
      the future will change, based on earlier diagnosis and treatment aimed at mucosal
      healing rather than symptom improvement.

PMID- 18636658
TI  - The future of wireless capsule endoscopy.
AB  - We outline probable and possible developments with wireless capsule endoscopy. It
      seems likely that capsule endoscopy will become increasingly effective in
      diagnostic gastrointestinal endoscopy. This will be attractive to patients
      especially for cancer or varices detection because capsule endoscopy is painless
      and is likely to have a higher take up rate compared to conventional colonoscopy
      and gastroscopy. Double imager capsules with increased frame rates have been used
      to image the esophagus for Barrett's and esophageal varices. The image quality is
      not bad but needs to be improved if it is to become a realistic substitute for
      flexible upper and lower gastrointestinal endoscopy. An increase in the frame
      rate, angle of view, depth of field, image numbers, duration of the procedure and
      improvements in illumination seem likely. Colonic, esophageal and gastric
      capsules will improve in quality, eroding the supremacy of flexible endoscopy,
      and become embedded into screening programs. Therapeutic capsules will emerge
      with brushing, cytology, fluid aspiration, biopsy and drug delivery capabilities.
      Electrocautery may also become possible. Diagnostic capsules will integrate
      physiological measurements with imaging and optical biopsy, and immunologic
      cancer recognition. Remote control movement will improve with the use of magnets
      and/or electrostimulation and perhaps electromechanical methods. External
      wireless commands will influence capsule diagnosis and therapy and will
      increasingly entail the use of real-time imaging. However, it should be noted
      that speculations about the future of technology in any detail are almost always
      wrong.

PMID- 18636659
TI  - Capsule endoscopy in celiac disease.
AB  - Video capsule endoscopy is an attractive and patient-friendly tool that provides
      high quality images of the small bowel. Obscure gastrointestinal bleeding is the
      primary and most evaluated indication to capsule endoscopy; however, indications
      are expanding and a small number of preliminary reports have been presented
      concerning the role of video capsule endoscopy in the diagnosis of celiac
      disease. The purpose of this review is to update the current knowledge and to
      hypothesize on future perspectives of the use of video capsule endoscopy in
      patients with celiac disease.

PMID- 18636660
TI  - Capsule endoscopy in pediatric patients.
AB  - Wireless capsule endoscope (WCE) for the investigation of the small bowel is an
      approved technique both in adults and children (more than 10 years old). The
      present review provides data on the indications, diagnostic yield, adverse events
      and limitations of the WCE technique in children and tries to predict the future
      of WCE usage in this population of patients.

PMID- 18636661
TI  - VEGF-D expression correlates with colorectal cancer aggressiveness and is
      downregulated by cetuximab.
AB  - AIM: To gain mechanistic insights into the role played by epidermal growth factor
      receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs)
      in colorectal cancer (CRC). METHODS: The impact of high-level expression of the
      growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands
      VEGF-C and VEGF-D on disease progression and prognosis in human CRC was
      investigated in 108 patients using immunohistochemistry. Furthermore, the
      expression of the lymphangiogenic factors in response to the modulation of EGFR
      signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at
      the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse
      xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF
      C and VEGF-D expression with varying intensities. VEGF-C expression was
      associated with histological grade. Strong expression of VEGF-D was significantly
      associated with lymph node metastases and linked to a trend for decreased
      survival in lymph node-positive patients. EGFR blockade with cetuximab resulted
      in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:
      In conclusion, the expression of VEGF-D in colorectal tumours is significantly
      associated with lymphatic involvement in CRC patients and such expression might
      be blocked effectively by cetuximab.

PMID- 18636662
TI  - Evaluation of mannitol effect in patients with acute hepatic failure and acute-on
      chronic liver failure using conventional MRI, diffusion tensor imaging and in
      vivo proton MR spectroscopy.
AB  - AIM: To evaluate the effect of an intravenous bolus of mannitol in altering brain
      metabolites, brain water content, brain parenchyma volume, cerebrospinal fluid
      (CSF) volume and clinical signs in controls and in patients with acute liver
      failure (ALF) and acute-on-chronic liver failure (ACLF), by comparing changes in
      conventional magnetic resonance imaging (MRI), in vivo proton magnetic resonance
      spectroscopy (PMRS) and diffusion tensor imaging (DTI) before and after its
      infusion. METHODS: Five patients each with ALF and ACLF in grade 3 or 4 hepatic
      encephalopathy and with clinical signs of raised intracranial pressure were
      studied along with five healthy volunteers. After baseline MRI, an intravenous
      bolus of 20% mannitol solution was given over 10 min in controls as well as in
      patients with ALF and ACLF. Repeat MRI for the same position was acquired 30 min
      after completing the mannitol injection. RESULTS: No statistically significant
      difference was observed between controls and patients with ALF and ACLF in
      metabolite ratios, DTI metrics and brain volume or CSF volume following 45 min of
      mannitol infusion. There was no change in clinical status at the end of post
      mannitol imaging. CONCLUSION: The osmotic effect of mannitol did not result in
      significant reduction of brain water content, alteration in metabolite ratios or
      any change in the clinical status of these patients during or within 45 min of
      mannitol infusion.

PMID- 18636663
TI  - Immunohistochemical localization of glutathione S-transferase-pi in human
      colorectal polyps.
AB  - AIM: To investigate the distribution of the placental form of glutathione-S
      transferase (GST) in colon polyps in order to evaluate the role of GST-pi in
      these tissues. METHODS: Sixteen polyp tissues removed at colonoscopy were
      examined. Tissues were investigated histologically and ultrastructurally. GST-pi
      expression was also analysed immunohistochemically, using peroxidase anti
      peroxidase (PAP) method and immunogold labelling method, for light and electron
      microscope respectively. RESULTS: All polyp tissues examined were adenoma of low,
      mild and high- grade dysplasia as shown in the histopathological reports.
      Nevertheless, the examination of the above specimens with electron microscope
      revealed that 3 of 9 adenoma of mild dysplasia had ultrastuctural features
      similar to high-grade dysplasia adenoma. GST-pi was variably expressed in
      adenoma, with the lowest relative levels occurring in low-grade adenoma and the
      highest levels found in high-grade adenoma. GST-pi was located mainly in
      undifferentiated epithelial cells. GST-pi positive particles were found in the
      cytoplasm and especially in the nucleus adjacent to the nuclear membrane of these
      cells. CONCLUSION: The overexpression of GST-pi in mild-grade adenomas with
      significant subcellular changes and in the majority of high-grade dysplasia
      adenoma suggests that this might be related to the carcinogenetic proceeding.
      Immunohistochemical localization of GST-pi in combination with ultrastructural
      changes indicate that GST-pi might be a sensitive agent for the detection of
      preneoplastic transformations in adenoma.

PMID- 18636664
TI  - Endoscopic treatment of biliary complications after liver transplantation.
AB  - AIM: To evaluate the efficacy of endoscopic treatment in patients who undergo
      OLTx or LRLTx and develop biliary complications. METHODS: This is a prospective,
      observational study of patients who developed biliary complications, after OLTx
      and LRLTx, with duct-to-duct anastomosis performed between June 2003 and June
      2007. Endoscopic Retrograde Cholangiopancreatography (ERCP) was considered
      unsuccessful when there was evidence of continuous bile leakage despite
      endoscopic stent placement, or persistence of stenosis after 1 year, despite
      multiple dilatation and stent placement. When the ERCP failed, a percutaneous
      trans-hepatic approach (PTC) or surgery was adopted. RESULTS: From June 2003 to
      June 2007, 261 adult patients were transplanted in our institute, 68 from living
      donors and 193 from cadaveric donors. In the OLTx group the rate of complications
      was 37.3%, while in the LRLTx group was 64.7%. The rate of ERCP failure was 19.4%
      in the OLTx group and 38.6% in LRLTx group. In OLTx group, 1 patient was re
      transplanted and 8 patients died. In the LRLTx group, 2 patients underwent OLTx
      and 8 patients died. The follow-up was 23.3 +/- 13.13 mo and 21.02 +/- 14.10 mo,
      respectively. CONCLUSION: Although ERCP is quite an effective mode of managing
      post-transplant bile duct complications, a significant number of patients need
      other types of approach. Further prospective studies are necessary in order to
      establish whether other endoscopic protocols or new devices, could improve the
      current results.

PMID- 18636665
TI  - Pituitary hormone circadian rhythm alterations in cirrhosis patients with
      subclinical hepatic encephalopathy.
AB  - AIM: To analyze pituitary hormone and melatonin circadian rhythms, and to
      correlate hormonal alterations with clinical performance, hepatic disease
      severity and diagnostic tests used for the detection of hepatic encephalopathy in
      cirrhosis. METHODS: Twenty-six patients with cirrhosis were enrolled in the
      study. Thirteen patients hospitalized for systemic diseases not affecting the
      liver were included as controls. Liver disease severity was assessed by the Child
      Pugh score. All patients underwent detailed neurological assessment,
      electroencephalogram (EEG), brain magnetic resonance imaging (MRI), assays of
      pituitary hormone, cortisol and melatonin, and complete blood chemistry
      evaluation. RESULTS: Pituitary hormone and melatonin circadian patterns were
      altered in cirrhosis patients without clinical encephalopathy. Circadian hormone
      alterations were different in cirrhosis patients compared with controls. Although
      cortisol secretion was not altered in any patient with cirrhosis, the basal
      cortisol levels were low and correlated with EEG and brain MRI abnormalities.
      Melatonin was the only hormone associated with the severity of liver
      insufficiency. CONCLUSION: Abnormal pituitary hormone and melatonin circadian
      patterns are present in cirrhosis before the development of hepatic
      encephalopathy. These abnormalities may be early indicators of impending hepatic
      encephalopathy. Factors affecting the human biologic clock at the early stages of
      liver insufficiency require further study.

PMID- 18636666
TI  - Tongue-like Barrett's esophagus is associated with gastroesophageal reflux
      disease.
AB  - AIM: To test this hypothesis of barrett esophagus (BE) classified into two types
      and to further determine if there was any correlation between the shape of
      endoscopically suspected esophageal metaplasia (ESEM), prevalence of reflux
      esophagitis (RE) and heartburn. METHODS: A total of 6504 Japanese who underwent
      endoscopy for their annual stomach check-up were enrolled in this study. BE was
      detected without histological confirmation that is ESEM. We originally classified
      cases of ESEM into 3 types based on its shape: Tongue-like (T type), Dome-like (D
      type) and Wave-like (W type) ESEM. The respective subjects were prospectively
      asked to complete questionnaires concerning the symptoms of heartburn, dysphagia,
      and abdominal pain for a one-month period. RESULTS: ESEM was observed in 10.3% of
      6504 subjects (ESEM < 1 cm, 9.4%; 1 cm < or = ESEM < 3 cm, 1.7%; ESEM > or = 3
      cm, 0.5%). The frequency of ESEM was significantly higher in males compared with
      female subjects. Statistical analysis showed that the prevalence of heartburn and
      RE were significantly higher in the T type ESEM than in the W type ESEM (P <
      0.05). CONCLUSION: The T type ESEM was strongly asso-ciated with reflux symptoms
      and RE whereas the W type ESEM was not associated with GERD.

PMID- 18636667
TI  - Prevalence and clinical significance of SEN virus infection in patients with non
      A-E hepatitis and volunteer blood donors in Shanghai.
AB  - AIM: To explore the prevalence of SEN virus (SENV) in patients with non A-E
      hepatitis and volunteer blood donors in Shanghai. METHODS: According to the
      published gene sequences, primers from the conserved region were designed. Then,
      the prevalence of SEN virus in 30 samples from healthy voluntary blood donors and
      30 samples from patients with non A-E hepatitis were detected by nested-PCR of
      SENV-D/H. Some PCR products were cloned and sequenced. RESULTS: The specificity
      of genotype-specific PCR was confirmed by sequencing, the SENV DNA was detected
      in 53.3% of the patients with non A-E hepatitis and 10% of the blood donors. The
      prevalence of SENV-D/H viremia was significantly higher in patients with non A-E
      hepatitis than in blood donors (P = 0.0002). SENV-H subtype and SENV-D subtype
      were found in 2 and 1 samples, respectively from blood donors. SENV-H subtype,
      SENV D subtype, mixed SENV-D and SENV-H subtype were found in 8, 6 and 2 samples,
      respectively, from patients with non A-E hepatitis. CONCLUSION: The gene type of
      SENV in patients with non A-E hepatitis and blood donors in shanghai is D or H
      subtype, and transfusion is not the only transmitting form of SENV.

PMID- 18636668
TI  - Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal
      administration of chitosan nanoparticles containing human insulin gene.
AB  - AIM: To study the expression of human insulin gene in gastrointestinal tracts of
      diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin
      gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats
      through lavage and coloclysis, respectively. Fasting blood glucose and plasma
      insulin levels were measured for 7 d. Reverse transcription polymerase chain
      reaction (RT-PCR) analysis and Western blot analysis were performed to confirm
      the expression of human insulin gene. RESULTS: Compared with the control group,
      the fasting blood glucose levels in the lavage and coloclysis groups were
      decreased significantly in 4 d (5.63 +/- 0.48 mmol/L and 5.07 +/- 0.37 mmol/L vs
      22.12 +/- 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels
      were much higher (32.26 +/- 1.81 microIU/mL and 32.79 +/- 1.84 microIU/mL vs
      14.23 +/- 1.38 microIU/mL, respectively, P < 0.01). The human insulin gene mRNA
      and human insulin were only detected in the lavage and coloclysis groups.
      CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be
      successfully transfected to rats through gastrointestinal tract, indicating that
      chitosan is a promising non-viral vector.

PMID- 18636669
TI  - Effect of lymphadenectomy extent on advanced gastric cancer located in the cardia
      and fundus.
AB  - AIM: To analyze the prognostic impact of lymphade-nectomy extent in advanced
      gastric cancer located in the cardia and fundus. METHODS: Two hundred and thirty
      six patients with advanced gastric cancer located in the cardia and fundus who
      underwent D2 curative resection were analyzed retrospectively. Relationships
      between the numbers of lymph nodes (LNs) dissected and survival was analyzed
      among different clinical stage subgroups. RESULTS: The 5-year overall survival
      rate of the entire cohort was 37.5%. Multivariate prognostic variables were total
      LNs dissected (P < 0.0001; or number of negative LNs examined, P < 0.0001),
      number of positive LNs (P < 0.0001), T category (P < 0.0001) and tumor size (P =
      0.015). The greatest survival differences were observed at cutoff values of 20
      LNs resected for stage II (P = 0.0136), 25 for stage III(P < 0.0001), 30 for
      stage IV (P = 0.0002), and 15 for all patients (P = 0.0024). Based on the
      statistically assumed linearity as best fit, linear regression showed a
      significant survival enhancement based on increasing negative LNs for patients of
      stages III (P = 0.013) and IV (P = 0.035). CONCLUSION: To improve the long-term
      survival of patients with advanced gastric cancer located in the cardia and
      fundus, removing at least 20 LNs for stage II, 25 LNs for stage III, and 30 LNs
      for stage IV patients during D2 radical dissection is recommended.

PMID- 18636670
TI  - Predictive factors for lymph node metastasis in poorly differentiated early
      gastric cancer and their impact on the surgical strategy.
AB  - AIM: To identify the predictive clinicopathological factors for lymph node
      metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to
      further expand the possibility of using endoscopic mucosal resection (EMR) for
      the treatment of poorly differentiated EGC. METHODS: Data were collected from 85
      poorly-differentiated EGC patients who were surgically treated. Association
      between the clinicopathological factors and the presence of LNM was
      retrospectively analyzed by univariate and multivariate logistic regression
      analyses. RESULTS: Univariate analysis showed that tumor size (OR= 5.814, 95% CI
      = 1.050 - 32.172, P = 0.044), depth of invasion (OR=10.763, 95% CI=1.259 -
      92.026, P = 0.030) and lymphatic vessel involvement (OR= 61.697, 95% CI= 2.144 -
      175.485, P = 0.007) were the significant and independent risk factors for LNM.
      The LNM rate was 5.4%, 42.9% and 50%, respectively, in poorly differentiated EGC
      patients with one, two and three of the risk factors, respectively. No LNM was
      found in 25 patients without the three risk factors. Forty-four lymph nodes were
      found to have metastasis, 29 (65.9%) and 15 (34.1%) of the lymph nodes involved
      were within N1 and beyond N1, respectively, in 12 patients with LNM. CONCLUSION:
      Endoscopic mucosal resection alone may be sufficient to treat poorly
      differentiated intramucosal EGC (< or = 2.0 cm in diameter) with no
      histologically-confirmed lymphatic vessel involvement. When lymphatic vessels are
      involved, lymph node dissection beyond limited (D1) dissection or D1+ lymph node
      dissection should be performed depending on the tumor location.

PMID- 18636671
TI  - Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction
      of cyclooxygenase-2 negative colon cancer cell line SW480.
AB  - AIM: To investigate the effects of aspirin (acetylsalicylic acid) on
      proliferation and apoptosis of colorectal cancer cell line SW480 and its
      mechanism. METHODS: Cyclooxygenase (COX)-2 negative colorectal cancer cell line
      SW480 was treated with aspirin at concentrations of 2.5 mmol/L, 5.0 mmol/L, 10.0
      mmol/L for different periods in vitro. Anti-proliferation effect of aspirin on
      SW480 was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Cell cycle and apoptosis were observed by flow cytometry
      (FCM). Transmission electron microscope (TEM) was used for morphological study.
      Apoptosis-associated genes were detected by immunohistochemical staining and
      Western blotting. RESULTS: Aspirin inhibited SW480 proliferation and induced
      apoptosis in a dose- and time-dependent manner. Treatment with different
      concentrations of aspirin significantly increased the proportions of cells at the
      G(0)/G(1)phase and decreased the proportions of cells at the S- and G(2)/M phases
      in a concentration-dependent manner. Aspirin not only induced apoptosis but also
      caused cell necrosis at a high concentration as well. After treatment with
      aspirin, SW480 cells displayed typically morphological features of apoptosis and
      necrosis under TEM, and increased the Bcl-2 expression in cells, but the
      expression of Bax was down regulated. CONCLUSION: Aspirin inhibits proliferation
      and induces apoptosis of SW480 cells. Its anti-tumor mechanism may arrest cell
      cycle and shift Bax/Bcl-2 balance in cells.

PMID- 18636672
TI  - Successful photodynamic therapy for biliary papillomatosis: a case report.
AB  - Papillomatosis of the bile duct is a rare disease with a high risk of malignant
      transformation. Therapeutical options include partial hepatectomy and liver
      transplantation. A previously healthy 65-years old male developed jaundice and
      right upper abdominal quadrant pain in 1996. A villous adenoma of the distal bile
      duct was diagnosed. A Whipple procedure was performed. In 2002 the patient turned
      symptomatic again. Another adenoma was found in the right hepatic duct resulting
      in a right hepatectomy. Two years later the patient again developed cholestasis.
      After drainage of the left hepatic duct with a percutaneous transhepatic
      cholangial drainage (PTCD) catheter, a recurrent biliary adenomatosis was
      diagnosed by cholangioscopy. As there was no surgical option left, the patient
      received photodynamic therapy (PDT) for the recurrent biliary papillomatosis.
      Three mo after he received further photodynamic therapies, the bile duct
      epithelium appeared normal and the patient had no signs of adenomatosis, both
      macroscopically and histologically. The follow-up cholangioscopy in late 2005
      revealed only a small papilloma without the need for intervention. In early 2006,
      the patient died of multi organ failure without signs of extrahepatic cholestasis
      or cholangitis at the age of 75, 10 years after the diagnosis of biliary
      papillomatosis was established. The patient exceeded the average life expectancy
      of patients with biliary papillomatosis by far. Thus, PDT might be a sufficient
      therapeutic option for recurrent papillomatosis patients with no significant side
      effects.

PMID- 18636673
TI  - Chronic hepatitis C infection in a patient with bone marrow hypoplasia.
AB  - Chronic hepatitis C virus (HCV) infection is associated with multifarious extra
      hepatic manifestations; the most described and discussed being mixed
      cryoglobulinemia which is strongly related to B-cell lymphoproliferative
      disorders (LPDs). We present a case of chronic HCV infection and mixed
      cryoglobulinemia, with minimal liver involvement. The case is a 53-year-old
      patient who was diagnosed as having bone marrow hypoplasia at the age of three.
      She received several blood transfusions to normalize her haemoglobin. At the age
      of 31, she was diagnosed with rheumatoid arthritis on account of her diffuse
      joint pain and inflammation, elevated rheumatoid factor (RF) and Raynaud's
      phenomenon. Twenty years later, monoclonal gammopathy of IgG Lambda (one year
      later, changed to IgM Kappa) was detected during a routine examination. A bone
      marrow biopsy showed hypoplasia, Kappa positive B-lymphocytes and low-grade
      malignant lymphoma cells. PCR of the bone marrow aspirate was not contributory.
      No treatment was initiated owing to her poor bone marrow function and she is
      under regular follow-up.

PMID- 18636674
TI  - Hemobilia as the initial manifestation of cholangiocarcinoma in a hemophilia B
      patient.
AB  - Hemobilia is a rare manifestation of hemophilia and is usually iatrogenic
      following liver biopsy. There are only few reports of spontaneous hemobilia in
      hemophilia patients. Cholangiocarcinoma is a well-established cause of hemobilia.
      We describe a case of a 70-year-old male, with known haemophilia B and a past
      history of papillotomy, who presented with classical symptoms of hemobilia. The
      initial diagnostic work-up failed to demonstrate a potential cause of bleeding
      other than the coagulopathy. Three months later, he was readmitted to our
      hospital with a second episode of hemobilia. During the second work-up, a
      cholangiocarcinoma was diagnosed both by imaging studies and by a significant
      elevation of cancer antigen 19-9. Although hemobilia could be attributed to
      hemophilia, especially in a patient with previous papillotomy, an underlying
      malignancy of the biliary tree should be suspected.

PMID- 18636675
TI  - Successful laparoscopic splenectomy after living-donor liver transplantation for
      thrombocytopenia caused by antiviral therapy.
AB  - Although interferon (IFN) based therapy for recurrent hepatitis C virus (HCV)
      infection after liver transplantation has been widely accepted, it induces
      various adverse effects such as thrombocytopenia, resulting in its interruption.
      Recently, concomitant splenectomy at the time of living donor liver
      transplantation (LDLT) has been tried to overcome this problem, but this
      procedure leads to several complications such as excessive intraoperative
      bleeding and serious infection. A 60-year-old female received LDLT using a left
      lobe graft from her second son for liver failure caused by hepatitis C-related
      cirrhosis. Six months after LDLT, she was diagnosed as recurrent HCV infection by
      liver biopsy. IFN monotherapy was started from 7 mo after LDLT and her platelet
      count decreased to less than 50,000/microL, which thus made it necessary to
      discontinue the treatment. We decided to attempt laparoscopic splenectomy (LS)
      under general anesthesia. Since intra-abdominal findings did not show any
      adhesion formations around the spleen, LS could be successfully performed. After
      LS, since her platelet count immediately increased to 225,000/microL 14 d after
      operation, IFN therapy was restarted and we could convert the combination therapy
      of IFN and ribavirin, resulting in no detectable viral marker. In conclusion, LS
      can be performed safely even after LDLT, and LS after LDLT is a feasible and less
      invasive modality for thrombocytopenia caused by antiviral therapy.

PMID- 18636676
TI  - Ischemic colitis secondary to inferior mesenteric arteriovenous fistula and
      portal vein stenosis in a liver transplant recipient.
AB  - Arteriovenous fistula (AVF) involving the inferior mesenteric vessels is rare,
      and the affected patients usually present with abdominal pain, mass, or features
      of established portal hypertension. Colonic ischemia is a less common and more
      serious manifestation of AVF. We report a case of ischemic colitis secondary to
      inferior mesenteric AVF in a patient who underwent a previous liver
      transplantation, subsequently developed portal vein stenosis, and then presented
      with acute lower gastrointestinal bleeding. He underwent percutaneous
      transhepatic placement of a portal vein stent and left colectomy.

PMID- 18636677
TI  - Coexistence of esophageal blue nevus, hair follicles and basaloid sqamous
      carcinoma: a case report.
AB  - We present the case of a 57-year-old man who underwent esophagectomy for
      esophageal carcinoma found at barium meal and gastroscopic examination. He was
      diagnosed as esophageal basaloid squamous carcinoma (BSC) and gastric stromal
      tumor, which were associated with focal proliferation of
      melanocytes/pigmentophages and hair follicles in esophageal mucosa. Melanocytic
      hyperplasia (melanocytosis) has previously been recognized as an occasional
      reactive lesion, which can accompany esophageal inflammation and invasive
      squamous carcinoma. The present case is unusual because of its hyperplasia of not
      only melanocytes but also hair follicles. To our knowledge, this is the first
      report of esophageal blue nevus and hair follicle coexisting with BSC.

PMID- 18636678
TI  - Laparoscopic fenestration of multiple giant biliary mucinous cystadenomas of the
      liver.
AB  - Biliary cystadenomas of the liver are rare, cystic neoplasms of the biliary
      ductal system usually occur in middle aged women. We report a case of synchronous
      multiple huge biliary mucinous cystadenomas with unique features. This is,
      according to our knowledge, the first report in the literature about three
      synchronously occurring hepatobiliary cystadenomas. Cystadenomas have a strong
      tendency to recur, particularly following incomplete excision, and a potential of
      malignant transformation. A therapeutic re-evaluation may be necessary when the
      diagnosis of hepatobiliary cystadenoma is made after the operation and an open
      liver resection should be considered.

PMID- 18636679
TI  - Migration of bisphenol A from polycarbonate baby and water bottles into water
      under severe conditions.
AB  - The isotope dilution headspace solid-phase microextraction and gas chromatography
      mass spectrometry method for bisphenol A (BPA) developed previously was used
      successfully in a BPA migration study at 70 degrees C of polycarbonate baby and
      reusable water bottles recently sold in Canada by using the whole bottles instead
      of pieces cut from the bottles. Migration of BPA from the PC bottles heated at 70
      degrees C was found to increase over the time in the quadratic equations.
      Migration levels of BPA in water varied from 228 to 521 microg L (-1) or from
      0.26 to 0.90 microg cm (-2) after being heated at 70 degrees C for 6 days. The
      average migration rates of BPA from the PC bottles into water at 70 degrees C
      ranged from 1.84 to 4.83 ng cm (-2) h (-1).

PMID- 18636680
TI  - Optimization of solid-liquid extraction of resveratrol and other phenolic
      compounds from milled grape canes (Vitis vinifera).
AB  - Optimization of the solid-liquid extraction conditions for trans-resveratrol,
      trans--viniferin, ferulic acid, and total phenolics from milled grape canes has
      been investigated. The temperature and ethanol concentration were found to be
      major process variables for all responses, whereas the solvent to solid ratio was
      found not to be significant for any of the responses studied. The yields of trans
      resveratrol, trans--viniferin, and total phenolics increased with increasing
      temperature. Maximum yields of trans-resveratrol (4.25 mg/g dw), trans--viniferin
      (2.03 mg/g), and total phenolics (9.28 mg/g dw) were predicted from the
      combination of a moderate ethanol concentration (50-70%) and the highest
      temperature (83.6 degrees C), whereas an ethanol concentration of 35% at the
      lowest temperature studied (16.4 degrees C) was optimal for the extraction of
      ferulic acid (1.05 mg/g dw). Effective diffusivity values of resveratrol in the
      solid phase, D eff for different extraction conditions, were calculated by
      fitting the experimental results to a model derived from the Fick's second law.
      Effective diffusivity of resveratrol in the solid phase varied from 3.1 x 10 (
      13) to 26.6 x 10 (-13) m (2) s (-1) with changing extraction conditions. The
      increase in effective diffusivity of resveratrol was observed with increasing
      temperature, and the highest predicted level was obtained when using 54%
      ethanol/water mixture at 83.6 degrees C. The increase in ethanol concentration
      exhibited the favorable effect up to 50-55%, thereafter effective diffusivity
      decreased with a further increase in concentration.

PMID- 18636681
TI  - Phenolic antioxidants from green tea produced from Camellia taliensis.
AB  - The chemical constituents of green tea prepared from the leaves of Camellia
      taliensis (W. W. Smith) Melchior (Theaceae) were investigated for the first time.
      Of these, 19 phenolic compounds including 8 hydrolyzable tannins (1-8), 6
      catechin derivatives (9-14), 3 quinic acid aromatic esters (15-17), and 2 simple
      phenolics (18, 19) were identified, along with caffeine (20). Their antioxidant
      activities were evaluated by DPPH radical scavenging and tyrosinase inhibitory
      assays. Moreover, the chemical composition was compared with that in the
      cultivated tea plant, C. sinensis var. assamica, by HPLC analysis. It was noted
      that C. taliensis has similar chemical features with the cultivated tea plant;
      that is, both of them contain rich flavan-3-ols and caffeine. In addition, there
      are abundant hydrolyzable tannins as specific characteristic constituents
      contained in the leaves of C. taliensis. Therein, 1,2-di-O-galloyl-4,6-O-(S)
      hexahydroxydiphenoyl-beta-D-glucopyranose (8), as a major compound in C.
      taliensis, showed remarkable antioxidant activity. The results suggested that C.
      taliensis could be a valuable plant resource for the production of tea.

PMID- 18636682
TI  - Compositional and tissue modifications induced by the natural fermentation
      process in table olives.
AB  - Olive fruits contain high concentrations of phenols that include phenolic acids,
      phenolic alcohols, flavonoids, and secoiridoids. The final concentration of
      phenols is strongly affected by brine conditions. The factors involved in
      modification by brine are still partially unknown and can include hydrolysis of
      secoiridoid glucosides and the release of hydrolyzed products. In this study
      olives from various Italian cultivars were processed by natural fermentation
      (e.g., without a preliminary treatment of olives with NaOH) using a selected
      Lactobacillus strain. Processed olives are characterized by a low phenolic
      concentration of phenols, consisting mainly of phenyl alcohols, verbascoside, and
      the dialdehydic form of decarboxymethylelenolic acid linked to (3,4
      dihydroxyphenyl)ethanol (3,4-DHPEA-EDA), whereas a high level of phenols occurs
      in olive brine from all the cultivars studied. Olives of the Coratina cultivar,
      control and with fermentation by Lactobacillus pentosus 1MO, were analyzed in a
      frozen hydrated state by cryo scanning electron microscopy and energy-dispersive
      X-ray microanalysis, on both surface and transversal freeze-fracture planes.
      Structural modifications, found in olives after fermentation, may explain the
      phenol release in brine.

PMID- 18636683
TI  - Antioxidant and free radical scavenging properties of marennine, a blue-green
      polyphenolic pigment from the diatom Haslea ostrearia (Gaillon/Bory) Simonsen
      responsible for the natural greening of cultured oysters.
AB  - Among microalgae, the marine diatom Haslea ostrearia has the distinctive feature
      of synthesizing and releasing, into the surrounding environment, a blue-green
      polyphenolic pigment called marennine. The oyster-breeding industry commonly
      makes use of this natural phenomenon for the greening of oysters grown in the
      ponds of the French Atlantic coast. This article reports the in vitro antioxidant
      properties of pure marennine. Two kinds of evaluation systems were adopted to
      test the antioxidative activity of marennine: antioxidant capacity assays (beta
      carotene and thymidine protection assays and iron reducing power assay) and free
      radical scavenging assays (DPPH*, O2*-, and HO*). In almost all cases, marennine
      exhibited significantly higher antioxidative and free radical scavenging
      activities than natural and synthetic antioxidants commonly used in food, as
      shown by comparing median effective concentration (EC 50) values, for each test
      independently. This medium molecular weight polyphenol (around 10 kDa) from
      microalgae is thus a potentially useful natural antioxidant. Because of its blue
      coloring property and water solubility, it could also be used as a natural food
      coloring additive.

PMID- 18636685
TI  - Detection of genetically modified canola using multiplex PCR coupled with
      oligonucleotide microarray hybridization.
AB  - A rapid method was developed for concurrent screening of transgenic elements in
      GM canola. This method utilizes a single multiplex PCR coupled with an
      oligonucleotide DNA array capable of simultaneously detecting the 12 approved GM
      canola lines in Canada. The assay includes construct-specific elements for
      identification of approved lines, common elements (e.g., CaMV 35S promoter,
      Agrobacterium tumefaciens nos terminator, or nptII gene) for screening of
      approved or unapproved lines, a canola-specific endogenous gene, and endogenous
      genes from heterologous crops to serve as additional controls. Oligonucleotide
      probes were validated individually for functionality and specificity by
      amplification of specific transgene sequences from appropriate GM canola lines
      corresponding to each probe sequence, and hybridization of amplicons to the
      array. Each target sequence hybridized to its corresponding oligonucleotide probe
      and no significant cross-hybridization was observed. The limit of detection was
      examined for the GM lines GT73, T45, and MS8/RF3, and was determined to be 0.1%,
      0.1%, and 0.5%, respectively, well within the European food and feed labeling
      threshold level of 0.9% for approved GM product. Practically, the method was
      demonstrated to be effective for the detection of GM canola in several types of
      animal feed, as well as in commercial canola meal.

PMID- 18636684
TI  - Improving digestibility of soy flour by reducing disulfide bonds with
      thioredoxin.
AB  - The Kunitz trypsin inhibitor (KTI) and the Bowman-Birk inhibitor (BBI) of trypsin
      and chymotrypsin contain disulfide bonds. Glycinin, the major storage protein in
      soybeans also contains disulfide bonds. Treatment of soy white flour with a NADP
      thioredoxin system (NTS) effectively reduced disulfide bonds in soy flour and
      increased protein digestibility by trypsin and pancreatin as measured by the pH
      stat method. Treatment of soy flour with NTS increased the digestibility compared
      to soy white flour by 29.3 and 60.6% for trypsin and pancreatin, respectively.
      NTS-treated soy flour had similar digestibility by trypsin to autoclaved soy
      flour and casein, but digestibility by pancreatin was less than autoclaved soy
      flour and casein. The degree of reduction by NTS was highly correlated to the
      degree of hydrolysis (DH) by trypsin (R(2) = 0.93) and pancreatin (R(2) = 0.99).
      The DH of NTS-treated soy flour by trypsin is reflective of both inactivation of
      trypsin inhibitors and overall protein digestibility while pancreatin hydrolysis
      is reflective of only overall protein digestibility.

PMID- 18636686
TI  - Determination of free flavan-3-ol content in barley (Hordeum vulgare L.) air
      classified flours: comparative study of HPLC-DAD/MS and spectrophotometric
      determinations.
AB  - The determination of free flavan-3-ol compounds in barley flours (cv. Gotic) and
      two resulting milling fractions (fine fraction 57% and coarse fraction 43%, w/w)
      obtained by air classification of dehulled grain is herein described. The
      determinations were carried out using reversed phase high-performance liquid
      chromatography coupled with both diode array detection and ESI-MS compared with
      conventional spectrophotometric determinations (total phenolic compounds by the
      Folin-Ciocalteu method and free radical scavenging activity with the DPPH assay).
      Significant correlations among the HPLC quantification, the spectrophotometric
      data, and the antioxidant capacity of extracts were revealed by Pearson's
      analysis. Nine flavan-3-ols were identified by HPLC-MS. Catechins and their
      derivatives were found to make a substantial contribution to the antioxidant
      power of extracts. The coarse fraction showed larger concentrations of flavan-3
      ols (221%) with respect to the fine fraction. This was confirmed by the
      antioxidant activity of the analyzed flours. The coarse fraction showed the
      greatest antioxidant activity (1200.1 +/- 66.2 micromol of Trolox equiv/100 g of
      flour) with respect to whole meal and fine fraction (1025.9 +/- 18.3 and 761.7 +/
      55.3 micromol of Trolox equiv/100 g of flour, respectively).

PMID- 18636687
TI  - Antioxidant and chemopreventive properties of polyphenolic compounds derived from
      Greek legume plant extracts.
AB  - Recently, phytochemical compounds present in legumes have gained a lot of
      interest because they are considered to be possible chemopreventive agents. In
      the present study, 14 polyphenolic compounds were extracted and identified from
      two unique varieties of Leguminosae family plants cultivated in Greece and
      screened for their antioxidant and chemopreventive properties. Ten polyphenolic
      fractions, which are mainly mixtures of two compounds and five pure flavonoids,
      were isolated from the methanolic extracts of aerial plant parts of Vicia faba
      and Lotus edulis (Leguminosae), respectively. All of these fractions exhibited
      significant DPPH(*) radical scavenging capacity. Furthermore, they exerted
      significant protective activity against free radical-induced DNA damage. This
      activity was more potent against ROO(*) radical-induced DNA damage than against
      that induced by OH(*) radicals. Finally, they exhibited significant ability to
      inhibit the activity of the topoisomerase I enzyme. These results imply that the
      polyphenolic compounds identified in the fractions were responsible of the
      observed properties of the fractions and the initial extracts and indicate
      different mechanisms by which these phenolic compounds may act as chemopreventive
      agents.

PMID- 18636688
TI  - Baking performance of synthetic glycolipids in comparison to commercial
      surfactants.
AB  - To gain insight into structure-activity relationships of glycolipids in
      breadmaking monogalactosyl dilinoleylglycerol ( 8) and monogalactosyl
      monolinoleylglycerol ( 6) were synthesized. Then their functional properties in
      dough and breadmaking were compared to those of commercial surfactants such as
      lecithins (from soybean, rapeseed, and sunflower), diacetyltartaric acid esters
      of monoglycerides (DATEM), monoglycerides, and sodium stearoyl-2-lactylate.
      Chemical synthesis of the galactolipids consisted of a four-step reaction
      pathway, yielding amounts of 1-1.5 g suitable for the determination of the
      functional properties. Variation of the acylation time in the third step provided
      either the monoacyl ( 6) or the diacyl compound ( 8). The functional properties
      were determined by means of rheological and baking tests on a microscale (10 g of
      flour). The synthetic galactolipids both displayed an excellent baking
      performance, with 6 having by far the best baking activity of all examined
      surfactants. The baking activities of 8, DATEM, and the monoglycerides were in
      the same range, whereas sodium stearoyl-2-lactylate was less active. Although the
      lecithins gained similar maxima in bread volume increases as the synthetic
      surfactants did, considerably higher concentrations were required to do so. An
      antistaling effect was found for only 6 and not for 8. However, this effect was
      weaker than for sodium stearoyl-2-lactylate and the monoglycerides.

PMID- 18636689
TI  - Facile immobilization of evolved agrobacterium radiobacter carbamoylase with high
      thermal and oxidative stability.
AB  - Optically pure amino acids have been widely used as intermediates in the
      synthesis of antibiotics, antifungal agents, pesticides, and sweeteners. Of
      particular importance, d- p-hydroxyphenylglycine (D-HPG) can be produced from d,
      l-hydroxyphenly hydantoin (D,L-HPH) in a two-step reaction mediated by d
      hydantoinase and N-carbamoyl- d-amino acid amidohydrolase (or carbamoylase). To
      make this production more industrially appealing, the carbamoylase gene from
      Agrobacterium radiobacter NRRL B11291 cloned in an Escherichia coli strain was
      intensively mutated to improve the thermal stability of carbamoylase by three
      rounds of DNA shuffling. After an extensive screening of the mutant library, the
      mutant E. coli strain M303 was obtained to produce variant carbamoylase, CBL303,
      with three critical mutated residues, including V40A, G75S, and V237A. Further
      characterization showed that in comparison with the wild-type counterpart the
      evolved carbamoylase exhibited more than 20-fold tolerance to heat and, in
      addition, hydrogen peroxide as a result of the synergistic effect caused by the
      three mutations. Moreover, with the fusion of the chitin-binding domain (ChBD) of
      Chitinase A1, the evolved carbamoylase CBL303 was specifically adsorbed on chitin
      beads. Subsequent analysis indicated that the linkage between the enzyme and the
      affinity matrix was substantially stable. The half-life of the immobilized
      carbamolyase CBL303 could reach 210 h at 45 degrees C, whereas its free form had
      that of 17 h. In particular, when applied to D-HPG production, the immobilized
      enzyme could be recycled 16 times with the achievement of 100% conversion yield.
      Along with the previous illustration of d-hydantoinase immobilization, the
      success achieved by immobilization of the evolved carbamoylase in this work
      apparently offers a promising way for the efficient production of D-HPG from D,L
      HPH.

PMID- 18636690
TI  - Structural basis for the potent calpain inhibitory activity of peptidyl alpha
      ketoacids.
AB  - A series of peptidyl alpha-ketoacids and alpha-ketoesters was synthesized and
      studied as mu-calpain inhibitors. Docking studies revealed that the mu-calpain
      inhibitory activity of the compounds is influenced by hydrogen bonding
      interactions and the potential for ionic interaction with active site residues as
      well as placement of a planar N-terminal capping group into the S 3 pocket of the
      enzyme.

PMID- 18636691
TI  - Ground- and excited-state aromaticity and antiaromaticity in benzene and
      cyclobutadiene.
AB  - The aromaticity and antiaromaticity of the ground state (S 0), lowest triplet
      state (T 1), and first singlet excited state (S 1) of benzene, and the ground
      states (S 0), lowest triplet states (T 1), and the first and second singlet
      excited states (S 1 and S 2) of square and rectangular cyclobutadiene are
      assessed using various magnetic criteria including nucleus-independent chemical
      shifts (NICS), proton shieldings, and magnetic susceptibilities calculated using
      complete-active-space self-consistent field (CASSCF) wave functions constructed
      from gauge-including atomic orbitals (GIAOs). These magnetic criteria strongly
      suggest that, in contrast to the well-known aromaticity of the S 0 state of
      benzene, the T 1 and S 1 states of this molecule are antiaromatic. In square
      cyclobutadiene, which is shown to be considerably more antiaromatic than
      rectangular cyclobutadiene, the magnetic properties of the T 1 and S 1 states
      allow these to be classified as aromatic. According to the computed magnetic
      criteria, the T 1 state of rectangular cyclobutadiene is still aromatic, but the
      S 1 state is antiaromatic, just as the S 2 state of square cyclobutadiene; the S
      2 state of rectangular cyclobutadiene is nonaromatic. The results demonstrate
      that the well-known "triplet aromaticity" of cyclic conjugated hydrocarbons
      represents a particular case of a broader concept of excited-state aromaticity
      and antiaromaticity. It is shown that while electronic excitation may lead to
      increased nuclear shieldings in certain low-lying electronic states, in general
      its main effect can be expected to be nuclear deshielding, which can be
      substantial for heavier nuclei.

PMID- 18636692
TI  - Neutral and charged excited states in polar organic films: origin of unusual
      electroluminescence in tri-p-tolylamine-based hole conductors.
AB  - The photoluminescence (PL) and electroluminescence (EL) of thin films of 1,1
      bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC) are remarkably different. Similar
      PL and EL are instead observed in films of the closely related donors tri- p
      tolylamine (TTA) and N, N'-diphenyl- N, N'-bis(3-methylphenyl)-(1,1'-biphenyl)
      4,4'-diamine (TPD). Such films show a wide range of hole transport that depends
      on the morphology and on external parameters such as temperature and electric
      field. Restricted configuration-interaction calculations performed on TTA, TAPC,
      TPD, and radical ions of TTA indicate that the unusual EL of TAPC films is due to
      direct recombination from a low-lying charge-transfer (CT) state. The CT state is
      strongly stabilized by electrostatic interactions with the polar environment.
      Theory confirms that TAPC can be considered a dimer of TTA. The charge
      distributions of TTA (+) and TTA (-) indicate charge localization in the anion
      that rationalizes low electron mobility as well as a strong charge-induced-dipole
      stabilization of the CT state.

PMID- 18636693
TI  - Searching for conical intersections of potential energy surfaces with the ONIOM
      method: application to previtamin D.
AB  - We demonstrate that the ONIOM method can be used to optimize a conical
      intersection between the ground and first excited-state potential energy surfaces
      of previtamin D (precalciferol), with excitation localized in a small part of the
      molecule: the hexatriene chromophore. These calculations were up to 100 times
      faster with little loss of accuracy compared to a full non-ONIOM Target
      calculation. The most accurate ONIOM method combination was CASSCF/4
      31G//ROHF/STO-3G(Triplet): in comparison to the Target (CASSCF/4-31G), bond
      lengths and angles in the hexatriene model region were calculated to within 0.02
      A and 0.7 degrees , respectively, and the energy difference between the conical
      intersection and nearest associated S 1 minimum to within 0.5 kcal x mol (-1).
      All of the low-level methods selected produced accurate geometries, including the
      UFF molecular mechanics and AM1 semiempirical methods, suggesting a cheap and
      efficient way of initially optimizing conical intersections geometries.
      Furthermore, ONIOM allows for an assessment of the localization of excited
      states, providing some fundamental insight into the physical processes involved.

PMID- 18636694
TI  - Experimental and ab initio dynamical investigations of the kinetics and
      intramolecular energy transfer mechanisms for the OH + 1,3-butadiene reaction
      between 263 and 423 K at low pressure.
AB  - The rate constants for the reaction of the OH radical with 1,3-butadiene and its
      deuterated isotopomer has been measured at 1-6 Torr total pressure over the
      temperature range of 263-423 K using the discharge flow system coupled with
      resonance fluorescence/laser-induced fluorescence detection of OH. The measured
      rate constants for the OH + 1,3-butadiene and OH + 1,3-butadiene- d 6 reactions
      at room temperature were found to be (6.98 +/- 0.28) x 10 (-11) and (6.94 +/-
      0.38) x 10 (-11) cm (3) molecule (-1) s (-1), respectively, in good agreement
      with previous measurements at higher pressures. An Arrhenius expression for this
      reaction was determined to be k 1 (II)( T) = (7.23 +/- 1.2) x10 (-11)exp[(664 +/-
      49)/ T] cm (3) molecule (-1) s (-1) at 263-423 K. The reaction was found to be
      independent of pressure between 1 and 6 Torr and over the temperature range of
      262- 423 K, in contrast to previous results for the OH + isoprene reaction under
      similar conditions. To help interpret these results, ab initio molecular dynamics
      results are presented where the intramolecular energy redistribution is analyzed
      for the product adducts formed in the OH + isoprene and OH + butadiene reactions.

PMID- 18636695
TI  - Anomalously large difference in dipole moment of isomers with nearly identical
      thermodynamic stability.
AB  - Sulfuric acid is a primary atmospheric nucleation precursor, with the ability to
      form stable aqueous hydrogen-bonded clusters/complexes. The electrical dipole
      moment of such clusters/complexes is important for ion-induced nucleation,
      largely controlled by dipole-charge interaction of airborne ions with vapor
      monomers and pre-existing clusters. Although experiments typically trace a single
      lowest energy conformer at low temperatures, the present study shows that the
      immediate vicinity (<1 kcal mol (-1)) of the global minima may be populated with
      a number of isomers of nearly identical spectral characteristics and drastically
      different dipole moments. The difference in the dipole moment of mono-, di-, and
      trihydrates of the sulfuric acid exceeds 1.3-1.5 Debyes ( approximately 50-60%),
      1.4-2.6 Debyes ( approximately 50-90%), and 3.8-4.2 Debyes ( approximately 370
      550%), respectively. Being driven by the temperature dependence of the Boltzmann
      distribution, the difference between the Boltzmann-Gibbs average dipole moment
      and the dipole moment of the most stable isomer increases with the ambient
      temperature, leading to large variations in the dipole-ion interaction strength,
      which may have important implications for the ion-mediated production of
      ultrafine aerosol particles associated with various climatic and health impacts.

PMID- 18636696
TI  - Spectroscopic investigations of high-power laser-induced dielectric breakdown in
      gas mixtures containing carbon monoxide.
AB  - Large-scale plasma was created in gas mixtures containing carbon monoxide by high
      power laser-induced dielectric breakdown (LIDB). The composition of the mixtures
      used corresponded to a cometary and/or meteoritic impact into the Earth's early
      atmosphere. A multiple-centimeter-sized fireball was created by focusing a single
      85 J, 450 ps near-infrared laser pulse into the center of a 15 L gas cell. The
      excited reaction intermediates that formed in various stages of the LIDB plasma
      chemical evolution were investigated by optical emission spectroscopy (OES) with
      temporal resolution. Special attention was paid to any OES signs of molecular
      ions. However, carbon monoxide cations were registered only if their production
      was enhanced by Penning ionization, i.e., excess He was added to the CO. The
      chemical consequences of laser-produced plasma generation in a CO-N 2-H 2O
      mixture were investigated using high resolution Fourier-transform infrared
      absorption spectroscopy (FTIR) and gas chromatography (GC). Several simple
      inorganic and organic compounds were identified in the reaction mixture exposed
      to ten laser sparks. H 2 (18)O was used to avoid possible contamination. The
      large laser spark triggered more complex reactivity originating in carbon
      monoxide than expected, when taking into account the strong triple bond of carbon
      monoxide causing typically inefficient dissociation of this molecule in
      electrical discharges.

PMID- 18636697
TI  - Parallel and coupled perpendicular transitions of RbCs 640 nm system: mass
      resolved resonance enhanced two-photon ionization in a cold molecular beam.
AB  - We have investigated the RbCs 640 nm system by mass-resolved resonance enhanced
      two-photon ionization in a cold molecular beam. Very complex vibronic structures
      were observed between 15420 and 15990 cm (-1). The parallel transitions of 2
      (3)Pi 0 v' = 4-20 <-- X (1)Sigma (+) v'' = 0 were identified by rotationally
      resolved spectra. Molecular constants and a Rydberg-Klein-Rees potential energy
      curve of the 2 (3)Pi 0 state were determined. The regular vibrational spacing of
      the parallel transition indicated that the 2 (3)Pi 0 state is not significantly
      perturbed by nearby excited electronic states. The complexity of the observed
      vibronic structures has been attributed to the coupled perpendicular transitions
      of 2 (1)Pi, 2 (3)Pi 1, and 3 (3)Sigma 1 (+) <-- X (1)Sigma (+) v'' = 0. For the
      perpendicular bands observed in the lower-energy spectral region between 15420
      and 15630 cm (-1) where the onsets of the 2 (3)Pi 1 and 3 (3)Sigma 1 (+) <-- X
      (1)Sigma (+) transitions are located, the upper electronic states and the
      vibrational quantum numbers were assigned. Perturbations of 2 (3)Pi 1-3 (3)Sigma
      1 (+) and 2 (1)Pi-3 (3)Sigma 1 (+) have been identified by the observed level
      shifts.

PMID- 18636698
TI  - Conformational behavior of cinchonidine revisited: a combined theoretical and
      experimental study.
AB  - Conformational space of cinchonidine has been explored by means of ab initio
      potential and free energy surfaces, and the temperature-induced changes of
      conformational populations were studied by a combined NOESY-DFT analysis. The DFT
      derived potential energy surface investigation identified four new conformers.
      Among them, Closed(7) is substantially relevant to fully understand the
      conformational behavior. The energy surfaces gave access to the favored
      transformation pathways at different temperatures (280-320 K). They also revealed
      the reasons for the negligible presence of energetically stable conformers and
      explained the experimentally observed temperature dependence of the populations.

PMID- 18636699
TI  - Infrared spectra of the sulfenic ester CH3SOCH3 and its photodissociation
      products in solid argon.
AB  - UV light irradiation of dimethyl sulfoxide (DMSO) in low temperature solid argon
      matrix produces sulfenic ester, CH 3SOCH 3, a high energy structural isomer of
      DMSO. The sulfenic ester molecule further dissociates to the CH 2O-CH 3SH complex
      under 266 nm laser irradiation. The CH 2S-CH 3OH complex is also formed upon UV
      light irradiation. The infrared spectra of the aforementioned species are
      assigned on the basis of isotopic substitutions ( (13)C and deuterium) as well as
      density functional frequency calculations.

PMID- 18636700
TI  - Metal speciation dynamics in monodisperse soft colloidal ligand suspensions.
AB  - A comprehensive theory is presented for the dynamics of metal speciation in
      monodisperse suspensions of soft spherical particles characterized by a hard core
      and an ion-permeable shell layer where ligands L are localized. The heterogeneity
      in the binding site distribution leads to complex formation/dissociation rate
      constants (denoted as k a (*) and k d (*), respectively) that may substantially
      differ from their homogeneous solution counterparts (k a and k d). The
      peculiarities of metal speciation dynamics in soft colloidal ligand dispersions
      result from the coupling between diffusive transport of free-metal ions M within
      and around the soft surface layer and the kinetics of ML complex
      formation/dissociation within the shell component of the particle. The
      relationship between k a,d (*) and k a,d is derived from the numerical evaluation
      of the spatial, time-dependent distributions of free and bound metal. For that
      purpose, the corresponding diffusion equations corrected by the appropriate
      chemical source term are solved in spherical geometry using a Kuwabara-cell-type
      representation where the intercellular distance is determined by the volume
      fraction of soft particles. The numerical study is supported by analytical
      approaches valid in the short time domain. For dilute dispersions of soft ligand
      particles, it is shown that the balance between free-metal diffusion within and
      outside of the shell and the kinetic conversion of M into ML within the
      particular soft surface layer rapidly establishes a quasi-steady-state regime.
      For sufficiently long time, chemical equilibrium between the free and bound metal
      is reached within the reactive particle layer, which corresponds to the true
      steady-state regime for the system investigated. The analysis reported covers the
      limiting cases of rigid particles where binding sites are located at the very
      surface of the particle core (e.g., functionalized latex colloids) and polymeric
      particles that are devoid of a hard core (e.g., polysaccharide macromolecules,
      gel particles). For both the transient and quasi-steady-state regimes, the
      dependence of k a,d (*) on the thickness of the soft surface layer, the radius of
      the hard core of the particle, and the kinetic rate constants k a,d for
      homogeneous ligand solutions is thoroughly discussed within the context of
      dynamic features for colloidal complex systems.

PMID- 18636701
TI  - Gaseous rust: thermochemistry of neutral and ionic iron oxides and hydroxides in
      the gas phase.
AB  - The experimental and theoretical thermochemistry of the gaseous neutral and ionic
      iron oxides and hydroxides FeO, FeOH, FeO(2), OFeOH, and Fe(OH)(2) and of the
      related cationic water complexes Fe(H(2)O)(+), (H(2)O)FeOH(+), and
      Fe(H(2)O)(2)(+) is analyzed comprehensively. A combination of data for the
      neutral species with those of the gaseous ions in conjunction with some
      additional measurements provides a refined and internally consistent compilation
      of thermochemical data for the neutral and ionic species. In terms of heats of
      formation at 0 K, the best estimates for the gaseous, mononuclear FeO(m)H(n)(
      /0/+/2+) species with m = 1, 2 and n = 0-4 are Delta(f)H(FeO(-)) = (108 +/- 6)
      kJ/mol, Delta(f)H(FeO) = (252 +/- 6) kJ/mol, Delta(f)H(FeO(+)) = (1088 +/- 6)
      kJ/mol, Delta(f)H(FeOH) = (129 +/- 15) kJ/mol, Delta(f)H(FeOH(+)) = (870 +/- 15)
      kJ/mol, Delta(f)H(FeO(2)(-)) = (-161 +/- 13) kJ/mol, Delta(f)H(FeO(2)) = (67 +/-
      12) kJ/mol, Delta(f)H(FeO(2)(+)) = (1062 +/- 25) kJ/mol, Delta(f)H(OFeOH) = (-84
      +/- 17) kJ/mol, Delta(f)H(OFeOH(+)) = (852 +/- 23) kJ/mol, Delta(f)H(Fe(OH)(2)(
      )) = -431 kJ/mol, Delta(f)H(Fe(OH)(2)) = (-322 +/- 2) kJ/mol, and
      Delta(f)H(Fe(OH)(2)(+)) = (561 +/- 10) kJ/mol for the iron oxides and hydroxides
      as well as Delta(f)H(Fe(H(2)O)(+)) = (809 +/- 5) kJ/mol,
      Delta(f)H((H(2)O)FeOH(+)) = 405 kJ/mol, and Delta(f)H(Fe(H(2)O)(2)(+)) = (406 +/-
      6) kJ/mol for the cationic water complexes. In addition, charge-stripping data
      for several of several-iron-containing cations are re-evaluated due to changes in
      the calibration scheme which lead to Delta(f)H(FeO(2+)) = (2795 +/- 28) kJ/mol,
      Delta(f)H(FeOH(2+)) = (2447 +/- 30) kJ/mol, Delta(f)H(Fe(H(2)O)(2+)) = (2129 +/-
      29) kJ/mol, Delta(f)H((H(2)O)FeOH(2+)) = 1864 kJ/mol, and
      Delta(f)H(Fe(H(2)O)(2)(2+)) = (1570 +/- 29) kJ/mol, respectively. The present
      compilation thus provides an almost complete picture of the redox chemistry of
      mononuclear iron oxides and hydroxides in the gas phase, which serves as a
      foundation for further experimental studies and may be used as a benchmark
      database for theoretical studies.

PMID- 18636702
TI  - Classical trajectory study of the dynamics of the reaction of Cl atoms with
      ethane.
AB  - We present an electronic-structure and dynamics study of the Cl + C2H6 --> HCl +
      C2H5 reaction. The stationary points of the ground-state potential energy surface
      have been characterized using various electronic-structure methods and basis
      sets. Our best calculations, CCSD(T) extrapolated to the complete basis limit,
      using geometries and harmonic frequencies obtained at the MP2/aug-cc-pVTZ level,
      are in agreement with the experimental reaction energy. Ab initio information has
      been used to reparameterize a semiempirical Hamiltonian so that the predictions
      of the improved Hamiltonian agree with the higher-level calculations in key
      regions of the potential energy surface. The improved semiempirical Hamiltonian
      is then used to propagate quasiclassical trajectories. Computed kinetic energy
      release and scattering angle distributions at a collision energy of approximately
      5.5 kcal mol(-1) are in reasonable agreement with experiments, but no evidence
      was found for the low translational energy HCl products scattered in the backward
      hemisphere reported in recent experiments.

PMID- 18636704
TI  - Theoretical insights on the electronic properties of eosin Y, an organic dye for
      photovoltaic applications.
AB  - A theoretical analysis, based on density functional theory, has been carried out
      on the electronic properties of eosin yellowish (2',4',5',7'
      tetrabromofluorescein), a dye used for photovoltaic applications. In particular
      different oxidation states of the bare molecule as well as its complexes with a
      Zn dication have been considered, with the aim to gain some insights on its
      electro- and photochemical behavior. The calculations have been carried out both
      in the gas phase and in solution, this last modeled by a continuum model. Besides
      the agreement with the experimental data, our results allow for a better
      interpretation of the spectroscopic properties of this dye and their tuning by
      interaction with the solvent or metal atom in aqueous solution.

PMID- 18636703
TI  - Collisional deactivation of Ba 5d7p (3)D1 by noble gases.
AB  - Collisional deactivation of the 5d7p (3)D1 state of Ba by noble gases is studied
      by time- and wavelength-resolved fluorescence techniques. A pulsed, frequency
      doubled dye laser at 273.9 nm excites the 5d7p (3)D1 level from the ground state,
      and fluorescence at 364.1 and 366.6 nm from the 5d7p (3)D1 --> 6s5d (3)D1 and
      5d7p (3)D1 --> 6s5d (3)D2 transitions, respectively, is monitored in real time to
      obtain the deactivation rate constants. At 835 K these rate constants are as
      follows: He, (1.69 +/- 0.08) x 10(-9) cm(3) s(-1); Ne, (3.93 +/- 0.14) x 10(-10)
      cm(3) s(-1); Ar, (4.53 +/- 0.15) x 10(-10) cm(3) s(-1); Kr, (4.64 +/- 0.13) x 10(
      10) cm(3) s(-1); Xe, (5.59 +/- 0.22) x 10(-10) cm(3) s(-1). From time-resolved
      5d7p (3)D1 emission in the absence of noble gas and from the intercepts of the
      quenching plots, the lifetime of this state is determined to be 100 +/- 1 ns.
      Using time- and wavelength-resolved Ba emission with a low background pressure of
      noble gas, radiative lifetimes of several near-resonant states are determined
      from the exponential rise of the fluorescence signals. These results are as
      follows: 5d6d (3)D3, 28 +/- 3 ns; 5d7p (3)P1, 46 +/- 2 ns; 5d6d (3)G3, 21.5 +/-
      0.8 ns; 5d7p (3)F3, 48 +/- 1 ns. Integrated fluorescence signals are used to
      infer the relative rate constants for population transfer from the 5d7p (3)D1
      state to eleven near-resonant fine structure states.

PMID- 18636705
TI  - Conformationally specific vacuum ultraviolet mass-analyzed threshold ionization
      spectroscopy of alkanethiols: structure and ionization of conformational isomers
      of ethanethiol, isopropanethiol, 1-propanethiol, tert-butanethiol, and 1
      butanethiol.
AB  - Conformational isomers of alkanethiols are isolated in the molecular beam, and
      the conformer-specific ionization dynamics have been investigated using vacuum
      ultraviolet mass-analyzed threshold ionization (MATI) spectroscopy. Only a single
      conformer of ethanethiol is observed to give the adiabatic ionization potential
      (IP) of 9.2922 +/- 0.0007 eV for the gauche conformer. For isopropanethiol, IP is
      found to be 9.1426 +/- 0.0006 for the trans conformer and 9.1559 +/- 0.0006 eV
      for the gauche conformer. Only two major conformational isomers are identified
      for 1-propanethiol, giving an IP of 9.1952 +/- 0.0006 for the trans-gauche
      conformer and 9.2008 +/- 0.0006 eV for the gauche-gauche conformer. The tert
      butanethiol, as expected, has a single conformer with an IP of 9.0294 +/- 0.0006
      eV. For 1-butanethiol, there are a number of conformers, and the assignment of
      the MATI bands to each conformer turns out to be nontrivial. The spectral
      simulation using the Franck-Condon analysis based on the density functional
      theory (DFT) calculations has been used for the identification of each
      conformational isomer in the MATI spectrum. Each conformer undergoes its unique
      structural change upon ionization, as revealed in the vibration resolved MATI
      spectrum, providing the powerful method for the spectral identification of a
      specific conformational isomer. The conformer specificity in the ionization
      driven structural change reflects the role of the electron of the highest
      occupied molecular orbital (HOMO) in the conformational preference.

PMID- 18636706
TI  - How close can you get? Studies of ultrafast light-induced processes in ruthenium
      [60] fullerene dyads with short pyrazolino and pyrrolidino links.
AB  - Two pyrazoline- and one pyrrolidine-bridged Ru(II)bipyridine-[60]fullerene dyads
      have been prepared and studied by ultrafast time-resolved spectroscopy. A silver
      assisted synthesis route, in which Ag(I) removes the chlorides from the precursor
      complex Ru(bpy) 2Cl 2 facilitates successful coordination of the [60]fullerene
      substituted third ligand. Upon light excitation of the ruthenium moiety, the
      emission was strongly quenched by the fullerene. The main quenching mechanism is
      an exceptionally fast direct energy transfer ( k obs > 1 x 10 (12) s (-1) in the
      pyrazoline-bridged dyads), resulting in population of the lowest excited triplet
      state of fullerene. No evidence for electron transfer was found, despite the
      extraordinarily short donor-acceptor distance that could kinetically favor that
      process. The observations have implications on the ongoing development of devices
      built from Ru-polypyridyl complexes and nanostructured carbon, such as C 60 or
      nanotubes.

PMID- 18636707
TI  - 3D framework containing Cu4Br4 cubane as connecting node with strong
      ferroelectricity.
AB  - The methanolothermal reaction of (S)-1,4-diallyl-2-methylpiperazine (DAMP) with
      an excess CuBr affords a novel homochiral 3D framework (DAMP)3(Cu4Br4)2(H2O)3 (1)
      in which Cu4Br4 cubane acts as a connecting node to mimic the pure inorganic role
      in the ferroelectricity to enhance the remnant polarization value which is
      comparable to that of BaTiO3 synthesized by peptide-assisted synthesis.

PMID- 18636708
TI  - Direct oxidative cyanation based on the concept of site isolation.
AB  - On the basis of the concept of site isolation, we have successfully demonstrated
      direct oxidative cyanation of various organic compounds, which even have higher
      oxidation potentials compared to that of cyanide, by using a polystyrene
      supported quaternary ammonium cyanide.

PMID- 18636709
TI  - MHz unidirectional rotation of molecular rotary motors.
AB  - A combination of cryogenic UV-vis and CD spectroscopy and transient absorption
      spectroscopy at ambient temperature is used to study a new class of
      unidirectional rotary molecular motors. Stabilization of unstable intermediates
      is achieved below 95 K in propane solution for the structure with the fastest
      rotation rate, and below this temperature measurements on the rate limiting step
      in the rotation cycle can be performed to obtain activation parameters. The
      results are compared to measurements at ambient temperature using transient
      absorption spectroscopy, which show that behavior of these motors is similar over
      the full temperature range investigated, thereby allowing a maximum rotation rate
      of 3 MHz at room temperature under suitable irradiation conditions.

PMID- 18636710
TI  - Guest-dependent high pressure phenomena in a nanoporous metal-organic framework
      material.
AB  - The nanoporous metal-organic framework material Cu3(1,3,5
      benzenetricarboxylate)2(H2O)3.{guest} exhibits anomalous compression under
      applied pressure that is associated with the hyper-filling of the pore network.
      This behavior involves a dramatic transition between a "hard" regime (bulk
      modulus, Khard approximately 118 GPa), where the pressure-transmitting fluid
      penetrates the framework cavities, and a "soft" regime (Ksoft approximately 30
      GPa), where the guest-framework system compresses concertedly. Not only is the
      duality in compressibility triggered by the availability of potential guests but
      the size/penetrability of the guest molecules determines the pressure at which
      the hard-soft transition occurs. Specifically, the observed compression behavior
      depends on the size of the pressure-transmitting fluid molecules, the sample
      particle size (i.e., the extent of the pore network), and the rate at which the
      pressure is increased. The unprecedented pressure-induced phenomena documented
      here, illustrates the exotic high-pressure behaviors possible in this versatile
      class of advanced functional materials with broad implications for their
      structure-function relationships and accordingly their practical application.

PMID- 18636711
TI  - N-C bond formation of NO ligands on ruthenium complexes with concurrent vinylic C
      H activation and subsequent proton-induced reactivities of the resulting
      nitrosovinyl species.
AB  - The N-C coupling of ligating NO with 2-vinylpyridines, affording nitrosovinyl
      complexes, was found. This is of significance since the reaction process involves
      a C-H activation of the vinyl moiety and subsequent C-N bond formation.
      Furthermore, we show that the resulting nitrosovinyl complexes are chemically
      versatile and potentially valuable species. Protonation of the resulting
      nitrosovinyl complexes in refluxing alcohol afforded the alcohol-incorporated
      complexes, as well as the ketoimine species. It is interesting to note that a
      proton-induced reaction with PPh3 trapped their intermediates, leading to the
      explication of these reaction mechanisms.

PMID- 18636712
TI  - Controllable synthesis of Cu2S nanocrystals and their assembly into a
      superlattice.
AB  - Highly uniform Cu2S nanocrystals with controllable sizes and shapes (circular and
      elongated) have been synthesized through a novel water-oil interface confined
      reaction. They can self-assemble into highly ordered multilayer superlattices. By
      controlling the size and shape of building block nanocrystals, the packing
      symmetry of the superlattice can be engineered. For circular nanocrystals, both
      fcc and hcp multilayer superlattices are found in the sample. For elongated
      nanocrystals, they can also generate a close-packed layer and further stack into
      a multilayer superlattice. The dipole moment of the inner nanocrystals is useful
      for their stacking. This work provides a simple bottom-up approach to integrate
      nanocrystals, as well as to adjust the packing symmetry of the final
      superlattice, which may have potential applications for nanomaterials and
      nanodevices in the future.

PMID- 18636713
TI  - The helical structure of surfactant peptide KL4 when bound to POPC: POPG lipid
      vesicles.
AB  - KL 4 is a 21-residue peptide employed as a functional mimic of lung surfactant
      protein B, which successfully lowers surface tension in the alveoli. A
      mechanistic understanding of how KL 4 affects lipid properties has proven elusive
      as the secondary structure of KL 4 in lipid preparations has not been determined
      at high resolution. The sequence of KL 4 is based on the C-terminus of SP-B, a
      naturally occurring helical protein that binds to lipid interfaces. The spacing
      of the lysine residues in KL 4 precludes the formation of a canonical amphipathic
      alpha-helix; qualitative measurements using Raman, CD, and FTIR spectroscopies
      have given conflicting results as to the secondary structure of the peptide as
      well as its orientation in the lipid environment. Here, we present a structural
      model of KL 4 bound to lipid bilayers based on solid state NMR data. Double
      quantum correlation experiments employing (13)C-enriched peptides were used to
      quantitatively determine the backbone torsion angles in KL 4 at several
      positions. These measurements, coupled with CD experiments, verify the helical
      nature of KL 4 when bound to lipids, with (phi, psi) angles that differ
      substantially from common values for alpha-helices of (-60, -45). The average
      torsion angles found for KL 4 bound to POPC:POPG lipid vesicles are (-105, -30);
      this deviation from ideal alpha-helical structure allows KL 4 to form an
      amphipathic helix at the lipid interface.

PMID- 18636715
TI  - Dissecting the membrane binding and insertion kinetics of a pHLIP peptide.
AB  - When it is bound to lipid bilayers, the conformation and location of the membrane
      pH (low) insertion peptide (pHLIP) depend on pH. This unique feature allows us to
      explicitly measure the kinetics leading to different membrane-bound states of
      pHLIP using a model membrane and stopped-flow technique. Our results show that
      the membrane association kinetics of pHLIP are multiexponential and are
      consistent with a parallel membrane interaction mechanism. Interestingly, our
      results also show that the overall rate at which the membrane-inserted state is
      formed is almost identical to that of formation of the surface-bound state, while
      prebinding slows the rate of peptide insertion.

PMID- 18636716
TI  - N-methylation of peptides: a new perspective in medicinal chemistry.
AB  - The potential of peptides as drug candidates is limited by their poor
      pharmacokinetic properties. Many peptides have a short half-life in vivo and a
      lack of oral availability. Inspired by the excellent pharmacokinetic profile of
      cyclosporine, a natural, multiply N-methylated cyclic peptide, we envisioned
      multiple N-methylation as a promising way to rationally improve key
      pharmacokinetic characteristics. In this Account, we summarize our efforts toward
      modulating the properties of peptides by multiple N-methylation. As a first step,
      we simplified the synthesis of N-methylated amino acids in solution, by employing
      very mild conditions that could be tolerated by the diverse protecting groups
      required when working with naturally occurring amino acids. We also report the
      rapid and inexpensive syntheses of N-methylated peptides on a solid support; this
      facilitated the N-methyl scanning of bioactive peptides. Because of a lack of
      information regarding the conformational behavior of multiply N-methylated
      peptides, a complete library of N-methylated cyclic alanine pentapeptides was
      synthesized. The library provided valuable insight into the conformational
      modulation of cyclic peptides by N-methylation. This information is extremely
      valuable for the design of bioactive peptides and spatial screening of cyclic N
      methylated peptides. To demonstrate the applicability of N-methylation to highly
      active but poorly bioavailable peptides, we performed a full N-methyl scan of the
      cyclopeptidic somatostatin analog cyclo(-PFwKTF-), known as the Veber-Hirschmann
      peptide. We show here for the first time that the simple approach of multiple N
      methylation can drastically improve the metabolic stability and intestinal
      permeability of peptides, for example, resulting in 10% oral bioavailability for
      a tri-N-methylated Veber-Hirschmann peptide analog. In addition, we also describe
      a designed approach to N-methylated peptide library synthesis, which can
      accelerate the screening of N-methylated bioactive peptides. Finally, we find
      that multiple N-methylation of a cyclic hexapeptide integrin antagonist of GPIIb
      IIIa (alphaIIb beta3 integrin), cyclo(-GRGDfL-), increases the selectivity of
      this peptide toward different integrin subtypes. This result demonstrates the
      utility of multiple N-methylation in elucidating the bioactive conformation of
      peptides.

PMID- 18636717
TI  - Gas-surface reactions between pentakis(dimethylamido)tantalum and surface grown
      hyperbranched polyglycidol films.
AB  - We have investigated the growth of hyperbranched polyglycidol films, and their
      subsequent reaction with a transition metal coordination complex,
      pentakis(dimethylamido)tantalum, Ta[N(CH 3) 2] 5 using ellipsometry, contact
      angle measurements, atomic force microscopy and X-ray photoelectron spectroscopy
      (XPS). Up to thicknesses of approximately 150 A, the growth of polyglycidol is
      approximately linear with reaction time for growth activated using either sodium
      methoxide or an organic superbase. The reaction of Ta[N(CH 3) 2] 5 at room
      temperature with these layers depends strongly on their thickness--the amount of
      uptake of Ta by the surface increases with the thickness of the organic layer,
      and thicker films also lead to more extensive ligand exchange reactions (with the
      R-OH groups), with as many as 4 ligands being lost on the thicker organic films.
      Ta penetrates the surface of all films examined (thicknesses 30-84 A), but the
      average depth of the penetration is nearly independent of the thickness of the
      organic film, and it is approximately 15-25 A. Modification of the polyglycidol
      with an aminoalkoxysilane introduces a significant fraction of -NH 2 termination
      in the organic layer. Reactions of this layer with the Ta complex are quite
      different than those on an unmodified layer--now on average only a single ligand
      exchange reaction occurs, while on the unmodified surface as many as four ligands
      are exchanged.

PMID- 18636718
TI  - Topological and orbital-based mechanisms of the electronic stabilization of
      bis(diisopropylamino)cyclopropenylidene.
AB  - Previous analysis of the topology of the electron density of
      bis(dimethylamino)cyclopropenylidene as a model of the stable
      bis(diisopropylamino)cyclopropenylidene revealed mechanisms of induction/back
      polarization, sigma-aromaticity, and sigma-pi polarization to be responsible for
      the electronic stabilization of the divalent carbon C2 upon amino substitution on
      the 3MR. This work presents new data from molecular orbital calculations and a
      full analysis of the operative natural bond orbitals and their interactions. The
      discrepancies between these orbital-based stabilization mechanisms and the
      physical stabilization based upon the quantum theory of atoms in molecules are
      uncovered through the separation of electron localization and delocalization
      indices into contributions from orbitals of sigma- and pi-symmetry, as well as
      calculated nucleus-independent chemical shifts that determine the degree of sigma
      and pi-delocalization/aromaticity. Graphical representations of functions of the
      electron density mapped onto various pi-orbital isosurfaces serve to better
      visualize the underlying differences between mathematical orbital space and the
      real space of the electron density. This work also provides new insight into the
      topological-based mechanism through investigation of the changes in the virial of
      the electronic forces acting on the interatomic surfaces--forces that govern the
      bonding and stabilization within a molecule.

PMID- 18636719
TI  - Calculated band profiles of the OH-stretching transitions in water dimer.
AB  - We have calculated the band profiles of the OH-stretching fundamental and
      overtone transitions in the proton donor unit of the water dimer complex. We have
      used a local mode Hamiltonian that includes both OH-stretching and OO-stretching
      motion but separates these adiabatically. The variation of OH-stretching
      frequency and anharmonicity with OO displacement from equilibrium contributes to
      the effective OO-stretching potentials for each OH-stretching state. The
      resulting OO-stretching energy levels and wave functions are used to simulate the
      vibrational profile of each OH-stretching transition. The coupled cluster with
      singles, doubles, and perturbative triples ab initio method with an augmented
      triple-zeta correlation consistent basis set has been used to obtain the
      necessary parameters, potentials, and dipole moment functions. We find that the
      OO-stretching transitions associated with a given hydrogen bonded OH-stretching
      transition are spread significantly and this spread increases with overtone. The
      spread is minor for the free OH-stretching transition. The inclusion of the OO
      stretching mode has a limited effect on the overall OH-stretching band intensity.

PMID- 18636720
TI  - Relationship between the broad OH stretching band of methanol and hydrogen
      bonding patterns in the liquid phase.
AB  - The OH stretching (nu(OH)) band of methanol observed in condensed phase has been
      analyzed in terms of hydrogen-bonding patterns. Quantum chemical calculations for
      methanol clusters have revealed that broadening of the nu(OH) envelope is
      reasonably reproduced by considering nearest and next-nearest neighbor
      interactions through hydrogen bonding. Because the hydrogen bond formed between
      donor (D) and acceptor (A) is cooperatively strengthened or weakened by a newly
      formed hydrogen bond at D or A, we have proposed the following notation for
      hydrogen-bonding patterns of monohydric alcohols: a(D)DAd(A)a(A), where a is the
      number of protons accepted by D (a(D)) or A (a(A)), and d(A) is the number of
      protons donated by A. The indicator of the hydrogen-bond strength, which is given
      by M(OH) = a(D) + d(A) - a(A), is correlated well with the nu(OH) wavenumber of
      the methanol molecule D participating in the a(D)DAd(A)a(A) pattern. The
      correlation between M(OH) and the hydrogen-bonding energy of the a(D)DAd(A)a(A)
      pattern has also been deduced from the calculation results for the clusters. The
      nu(OH) bands of methanol measured in the CCl4 solution and pure liquid have been
      successfully analyzed by the method proposed here.

PMID- 18636721
TI  - Control of the coordination structure of organometallic palladium complexes in an
      apo-ferritin cage.
AB  - We report the preparation of organometallic Pd(allyl) dinuclear complexes in
      protein cages of apo-Fr by reactions with [Pd(allyl)Cl]2 (allyl = eta3-C3H5). One
      of the dinuclear complexes is converted to a trinuclear complex by replacing a Pd
      coordinated His residue to an Ala residue. These results suggest that
      multinuclear metal complexes with various coordination structures could be
      prepared by the deletion or introduction of His, Cys, and Glu at appropriate
      positions on protein surface.

PMID- 18636722
TI  - Luminescent and Raman active silver nanoparticles with polycrystalline structure.
AB  - We report the synthesis of silver nanoparticles with grain sizes down to electron
      Fermi wavelength. These nanoparticles exhibit bright luminescence and large Raman
      enhancement effect. The number of photons emitted from these nanoparticles
      exceeded that from quantum dots or dye molecules by approximately 2 or 5 orders
      of magnitude, respectively.

PMID- 18636724
TI  - Formation and bonding of alane clusters on Al(111) surfaces studied by infrared
      absorption spectroscopy and theoretical modeling.
AB  - Alanes are believed to be the mass transport intermediate in many hydrogen
      storage reactions and thus important for understanding rehydrogenation kinetics
      for alanates and AlH3. Combining density functional theory (DFT) and surface
      infrared (IR) spectroscopy, we provide atomistic details about the formation of
      alanes on the Al(111) surface, a model environment for the rehydrogenation
      reactions. At low coverage, DFT predicts a 2-fold bridge site adsorption for
      atomic hydrogen at 1150 cm(-1), which is too weak to be detected by IR but was
      previously observed in electron energy loss spectroscopy. At higher coverage,
      steps are the most favorable adsorption sites for atomic H adsorption, and it is
      likely that the AlH3 molecules form (initially strongly bound to steps) at
      saturation. With increasing exposures AlH3 is extracted from the step edge and
      becomes highly mobile on the terraces in a weakly bound state, accounting for
      step etching observed in previous STM studies. The mobility of these weakly bound
      AlH3 molecules is the key factor leading to the growth of larger alanes through
      AlH3 oligomerization. The subsequent decomposition and desorption of alanes is
      also investigated and compared to previous temperature programmed desorption
      studies.

PMID- 18636723
TI  - Synthesis and characterization of amino derivatives of persistent trityl radicals
      as dual function pH and oxygen paramagnetic probes.
AB  - Triarylmethyl radicals, TAMs, are useful soluble paramagnetic probes for EPR
      spectroscopic and imaging applications because of their extraordinary stability
      in living tissues, narrow line width, high analytical resolution at micromolar
      concentrations and enhanced sensitivity to molecular oxygen. Recently we proposed
      the concept of dual function pH and oxygen TAM probes based on the incorporation
      of ionizable groups into the TAM structure (J. Am. Chem. Soc. 2007, 129 (23),
      7240-7241). In this paper we report the synthesis of TAM derivatives containing
      amino groups. The synthesized TAMs combine stability with oxygen and pH
      sensitivity, in the range of pH from 6.8 to 9.0. To decrease the number of
      spectral components and improve probe solubility at physiological pH, asymmetric
      TAM derivatives containing both carboxyl and amino functions were synthesized.
      The presence of nitrogen and hydrogen atoms in direct proximity to protonatable
      amino groups resulted in strong pH-induced changes to the corresponding hyperfine
      splittings, Delta hfs approximately (300-1000) mG, comparable to the values of
      hfs themselves. Large pH-dependent line shifts of individual spectral components,
      with narrow linewidths of (160-280) mG, allow for easy discrimination between the
      pH effect and the observed oxygen-dependent line broadening of about (6 +/- 0.5)
      mG per % oxygen. The synthesized TAM derivatives represent the first dual
      function pH and oxygen paramagnetic probes with reasonably valuable properties
      for biomedical research.

PMID- 18636725
TI  - Observation of a hidden intermediate in the Stille reaction. Study of the
      reversal of the transmetalation step.
AB  - A study of the reaction of cis-[PdRf2(AsPh3)2] (Rf = 3,5-C6Cl2F3) with ISnBu3
      (that is the reversal of the natural Stille reaction of [PdRfI(AsPh3)2] with
      RfSnBu3) allows for the observation of cis-[PdRf2(AsPh3)(ISnBu3)], the expected
      intermediate from a cyclic transmetalation in the direct Stille reaction, thus
      providing experimental support to the operation of cyclic transmetalation
      pathways.

PMID- 18636726
TI  - A 64-nuclear cubic cage incorporating propeller-like Fe(III)8 apices and HCOO-
      edges.
AB  - A 64-nuclear cubic cage with corners of a propeller-like FeIII8 cluster and anti
      anti HCOO- edges displays strong antiferromagnetism resulting in a zero spin
      ground state.

PMID- 18636728
TI  - Orientational dependence of linear dichroism exemplified by dyed spherulites.
AB  - D-sorbitol forms so-called spherulites from under-cooled melts. These
      polycrystalline formations have optically uniaxial radii. Melts pressed between
      glasses crystallize as plane sections of spheres. Dyes that are soluble in molten
      sorbitol become oriented as the crystallization front passes through the melt so
      as to form disks with large linear dichroism in the absorption bands of the dyes.
      The dyeing of spherulites is thus a general method of solute alignment. The
      linear optical properties of sorbitol spherulites containing the azo dye amaranth
      were analyzed in detail so as to correct a persistent confusion in the literature
      regarding the orientational dependence of linear dichroism. In cases involving
      thin film dichroism of multilayered samples requiring many corrections of
      intensity data in non-normal incidence, some authors have taken transmittance and
      others absorbance as having a cosine-squared angular dependence on the plane of
      the electric vector of linearly polarized light. Plane sections of doped
      spherulites present all orientations of an electric dipole oscillator in
      spatially localized region in normal incidence. As such, the samples described
      herein are ideally suited to resolving this confusion. Images of transmittance of
      dyed spherulites in polarized light were recorded with a CCD camera and simulated
      under the assumption that both absorbance and transmittance show a cosine-squared
      angular dependence but with respect to different angles. Transmittance with a
      cosine-squared dependence follows azimuthal rotations of the spherulite radii
      around the wave vector, while absorbance with a cosine-squared dependence follows
      rotations about axes perpendicular to the wave vector, natural consequences of
      the properties of the optical indicatrix that are often overlooked. Spherulites
      obviate the substantial experimental complexities that are engendered in non
      normal incidence by sample reorientation. Thus, the principles of anisotropic
      absorption are given in a complete and intuitive fashion.

PMID- 18636729
TI  - Order-disorder antiferroelectric phase transition in a hybrid inorganic-organic
      framework with the perovskite architecture.
AB  - [(CH3)2NH2]Zn(HCOO)3, 1, adopts a structure that is analogous to that of a
      traditional perovskite, ABX3, with A = [(CH3)2NH2], B = Zn, and X = HCOO. The
      hydrogen atoms of the dimethyl ammonium cation, which hydrogen bond to oxygen
      atoms of the formate framework, are disordered at room temperature. X-ray powder
      diffraction, dielectric constant, and specific heat data show that 1 undergoes an
      order-disorder phase transition on cooling below 156 K. We present evidence that
      this is a classical paraelectric to antiferroelectric phase transition that is
      driven by ordering of the hydrogen atoms. This sort of electrical ordering
      associated with order-disorder phase transition is unprecedented in hybrid
      frameworks and opens up an exciting new direction in rational synthetic
      strategies to create extended hybrid networks for applications in ferroic-related
      fields.

PMID- 18636730
TI  - Kinetic investigation of porphyrin interaction with chiral templates reveals
      unexpected features of the induction and self-propagation mechanism of chiral
      memory.
AB  - Kinetics of the porphyrin aggregation leading to a chiral memory system shows a
      remarkable "catalytic" effect of the noncovalent templates explaining their self
      replication ability.

PMID- 18636731
TI  - Direct acylation of aryl bromides with aldehydes by palladium catalysis.
AB  - A new protocol for the direct acylation of aryl bromides with aldehydes is
      established. It appears to involve palladium-amine cooperative catalysis,
      affording synthetically important alkyl aryl ketones in moderate to excellent
      yields in a straightforward manner, and broadening the scope of metal-catalyzed
      coupling reactions.

PMID- 18636732
TI  - Bioavailability and tissue distribution of sesamol in rat.
AB  - Sesamol, generally regarded as the main antioxidative component in sesame oil,
      can be generated from sesamolin by roasting sesame seed or bleaching sesame oil.
      This paper reports the bioavailability of sesamol in Sprague-Dawley (SD) rats.
      Biological fluid was sampled following a dose of sesamol of 50 mg/kg by gastric
      gavage (p.o.) or by intravenous injection. The pharmacokinetic data of sesamol
      were calculated by noncompartmental model. The tissue distribution of sesamol
      (p.o., 100 mg/kg) in SD rats was also investigated. The concentration changes of
      sesamol were determined in various tissues and plasma within a 24 h period after
      oral administration of sesamol. The results showed that the oral bioavailability
      of sesamol was 35.5 +/- 8.5%. Sesamol was found to be able to penetrate the blood
      brain barrier and go through hepatobiliary excretion. Sesamol conjugated
      metabolites were widely distributed in SD rat tissues, with the highest
      concentrations in the liver and kidneys and the lowest in the brain. It is
      postulated that sesamol is incorporated into the liver first and then transported
      to the other tissues (lung, kidneys, and brain). The major metabolites of sesamol
      distributed in the lung and kidney were glucuronide and sulfate.

PMID- 18636733
TI  - Determination of adulteration in apple juice by HPLC with novel optical rotation
      detector.
AB  - A simple HPLC method for the determination of adulteration in apple juice was
      developed. The method is based on the detection of D-malate, derived from racemic
      malic acid, which is added as an acidulant. A variable-wavelength optical
      rotation detector was used to determine the enantiomeric excess (ee). Using anion
      exchange chromatography with a phosphate buffer eluent and UV (210 nm) detection,
      the limit of detection for L-malate was 2 microg. With an injection of 13.4
      microg of malate, the standard deviation of the ee calibration curve was 2.5%.
      Several apple juice samples were analyzed according to the proposed procedure,
      and the results agreed with those obtained using enzymatic kits for food
      analysis.

PMID- 18636734
TI  - Transcriptome response to glyphosate in sensitive and resistant soybean.
AB  - The majority of soybeans planted in the United States are resistant to glyphosate
      due to introduction of a gene encoding for a glyphosate-insensitive 5
      enolypyruvylshikimate-3-phosphate synthase. Gene expression profiling was
      conducted using cDNA microarrays to address questions related to potential
      secondary effects of glyphosate. When glyphosate-sensitive plants were treated
      with glyphosate, 3, 170, and 311 genes were identified as having different
      transcript levels at 1, 4, and 24 h post-treatment (hpt), respectively.
      Differentially expressed genes were classified into functional categories, and
      their possible roles in response to glyphosate are briefly discussed. Gene
      expression profiling of glyphosate-resistant plants treated with glyphosate
      indicated that the plants were marginally affected at 1 hpt and then quickly
      adjusted to glyphosate treatment. Ten, four, and four genes were identified as
      differentially expressed at 1, 4, and 24 hpt. When gene expression profiles of
      cotyledons from developing seed were compared between the near-isogenic resistant
      and sensitive lines, two genes were identified as significantly differentially
      expressed out of 27000, which was less than the empirical false-discovery rate
      determined from a control experiment. Quantitative real-time reverse-transcribed
      Polymerase Chain Reaction was conducted on selected genes and yielded results
      consistent with those from the microarrays. Collectively, these data indicate
      that there are no major transcriptomic changes associated with currently used
      glyphosate-resistant soybean.

PMID- 18636735
TI  - Isolation and characterization of immunostimulatory polysaccharide from an herb
      tea, Gynostemma pentaphyllum Makino.
AB  - Water-soluble polysaccharide from Gynostemma pentaphyllum herb tea (PSGP) was
      isolated by hot-water extraction and ethanol precipitation. The chemical
      components and preliminary immunomodulating activity of PSGP were investigated
      both in vitro and in vivo. Capillary zone electrophoresis analysis showed that
      PSGP was a typical nonstarch heteropolysaccharide, with glucose being the main
      component monosaccharide (23.2%), followed by galactose (18.9%), arabinose
      (10.5%), rhamnose (7.7%), galacturonic acid (4.7%), xylose (3.9%), mannose
      (3.1%), and glucuronic acid (1.2%). PSGP could significantly stimulate peritoneal
      macrophages to release nitric oxide, reactive oxygen species, and tumor necrosis
      factor-alpha in a dose-dependent manner. This immunostimulating activity of PSGP
      was further demonstrated by its inhibition on the proliferation of human colon
      carcinoma HT-29 and SW-116 cells incubated with the supernatant of PSGP
      stimulated macrophage culture. It is evident that PSGP is a very important
      ingredient responsible for at least in part the immunomodulating activity of G.
      pentaphyllum herb tea.

PMID- 18636736
TI  - Chemistry and physical properties of melt-processed and solution-cross-linked
      corn zein.
AB  - Corn zein was cross-linked with glutaraldehyde (GDA) using glacial acetic acid
      (HAc) as catalyst. The objectives are to evaluate the swelling characteristics of
      GDA cross-linked zein gels in water, ethanol, and their combinations. Similar
      formulations, upon solvent evaporation, form films. The mechanical properties of
      the films are compared to compression molded tensile bars from GDA melt-processed
      zein as a second objective. Chemistry of the cross-linking reaction was based on
      the aldehyde binding characteristics defined by use of fluorescence spectroscopy;
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to
      demonstrate the cross-linking reaction; FTIR to observe absorption differences of
      the cross-linked product; differential scanning calorimetry, dynamic mechanical
      analysis and thermogravimetric analysis to assess thermal properties; and the use
      of Instron Universal Testing Machine to evaluate mechanical properties. A
      reaction mechanism for acid catalyzed GDA cross-linking of zein is proposed.
      Thermal and mechanical properties of tensile bars cut from either film or formed
      by compression molding were similar, where both showed increased tensile
      strengths, ductility and stiffness when compared with unmodified controls.
      Samples that were reacted with 8% GDA by weight based on weight of zein from
      either process retained their integrity when tensile bars from each were
      subjected to boiling water for 10 min or soaking in either water or HAc for 24 h.
      The melt-processed, cross-linked zein is a more environmentally friendly method
      that would eliminate the need for HAc recovery.

PMID- 18636737
TI  - Antioxidant activity of oregano, parsley, and olive mill wastewaters in bulk oils
      and oil-in-water emulsions enriched in fish oil.
AB  - The antioxidant activity of oregano, parsley, olive mill wastewaters (OMWW),
      Trolox, and ethylenediaminetetraacetic acid (EDTA) was evaluated in bulk oils and
      oil-in-water (o/w) emulsions enriched with 5% tuna oil by monitoring the
      formation of hydroperoxides, hexanal, and t-t-2,4-heptadienal in samples stored
      at 37 degrees C for 14 days. In bulk oil, the order of antioxidant activity was,
      in decreasing order (p < 0.05), OMWW > oregano > parsley > EDTA > Trolox. The
      antioxidant activity in o/w emulsion followed the same order except that EDTA was
      as efficient an antioxidant as OMWW. In addition, the total phenolic content, the
      radical scavenging properties, the reducing capacity, and the iron chelating
      activity of OMWW, parsley, and oregano extracts were determined by the Folin
      Ciocalteau, oxygen radical absorbance capacity, ferric reducing antioxidant
      power, and iron(II) chelating activity assays, respectively. The antioxidant
      activity of OMWW, parsley, and oregano in food systems was related to their total
      phenolic content and radical scavenging capacity but not to their ability to
      chelate iron in vitro. OMWW was identified as a promising source of antioxidants
      to retard lipid oxidation in fish oil-enriched food products.

PMID- 18636738
TI  - Proanthocyanidins: target compounds as antibacterial agents.
AB  - Grape seeds accumulate in huge quantities as byproduct during wine production and
      are therefore a cheap source for pharmacologically active agents. However,
      studies prove poor antibacterial activity, and results of analyses are sometimes
      contradictory. The aim of this study was, thus, to determine the antibacterial
      activity of grape seed extracts with special focus on the chromatographic
      characterization of active fractions. In the course of these investigations,
      extraction protocols were optimized so that microwave-assisted extraction (MAE)
      guaranteed highest preconcentration efficiency. Proanthocyanidins, monomeric
      flavonoid aglycones, as well as some of their glycosides could be identified
      within yielded extracts via high-performance liquid chromatography-mass
      spectrometry (HPLC-MS). By that means the coherence number of possible isomers of
      procyanidins was approximated by a newly developed equation. As far as
      antibacterial activity determined via screening tests is concerned, the extracts
      generally have been found to be positively responsive toward 10 different gram
      positive and gram-negative bacteria strains. After fractionation of the raw
      extracts, proanthocyanidins P2, P3, P4 and gallate esters P2G and P3G (P =
      proanthocyanidin consisting of catechin and epicatechin units, n =
      oligomerization degree, G = gallate ester) were determined as active
      antibacterial agents toward 10 different pathogens. Only moderate activity was
      found for monomeric flavonoid fractions.

PMID- 18636739
TI  - Health-promoting effects of a dietary fiber concentrate from the soybean
      byproduct okara in rats.
AB  - Okara (a byproduct of the soy milk industry) is rich in proteins (24.5-37.5 g/100
      g of dry matter (dm)), lipids (9.3-22.3 g/100 g of dm), and dietary fiber (DF)
      (14.5-55.4 g/100 g of dm). It also contains isoflavones (0.14 g/100 g of dm). In
      the present study we fed female healthy Wistar rats either a standard rat diet or
      a supplemented 10% DF-rich okara (DFRO) diet for 4 weeks, and then we assessed
      several health parameters in the serum and the cecum compartments. In comparison
      to the control group, rats fed DFRO showed a significant decrease in weight gain
      (5.00 +/- 1.22 g vs 2.00 +/- 1.46 g, P < 0.03, during week 4) and in total
      cholesterol (65 +/- 8 mg/dL vs 51 +/- 5 mg/dL, P < 0.05) and a significantly
      increased antioxidant status (36.71 +/- 15.31 micromol of Trolox equivalents
      (TEs)/g vs 69.75 +/- 16.11 micromol of TEs/g, P < 0.0003) and butyrogenic effect
      (39.37%, P < 0.003) in the cecum. In addition, a significant enhancement in the
      apparent absorption (41.89 +/- 1.64% vs 47.02 +/- 2.51%, P < 0.004) and in the
      true retention (41.62 +/- 1.60% vs 46.68 +/- 2.55%, P < 0.005) of calcium was
      appreciated. In summary, these findings show for the first time that a
      concentrate DF from a soybean byproduct protects the gut environment in terms of
      antioxidant status and prebiotic effect. These results may highlight the
      development of an innovative soybean byproduct rich in DF which could be useful
      as a functional ingredient with health-promoting attributes.

PMID- 18636740
TI  - Synthesis of carbasugar C-1 phosphates via Pd-catalyzed cyclopropanol ring
      opening.
AB  - The stereoselective syntheses of 2,3-dideoxy-4-oxo-5a-carba-alpha- d
      rhamnopyanose 1-phosphate, 2,3-dideoxy-5a-carba-alpha- d-rhamnopyranose 1
      phosphate, 5a-carba-alpha- d-rhamnopyranose 1-phosphate, 5a-carba-beta- d
      digitoxopyranose 1-phosphate, and 5a-carba-alpha- l-rhamnopyranose 1-phosphate
      have been achieved from d-quinic acid. The routes rely upon a Simmons-Smith
      cyclopropanation and diastereospecific ring opening of cyclopropanol under Pd/C
      hydrogenation condition to set up the alpha-methyl ketone. A sequence of
      diastereoselective reduction, dihydroxylation, and/or Myers' reductive 1,3
      rearrangement were used to install the desired stereochemistry.

PMID- 18636741
TI  - Flexible strategy for the synthesis of pyrrolizidine alkaloids.
AB  - A general strategy for the production of pyrrolizidine alkaloids is described,
      starting from intermediate (+)-9. The key features are diastereoselective
      dihydroxylation, inversion at the ring junction by hydroboration of an enamine,
      and ring closure to form the bicyclo ring system. This route is attractive
      because of its brevity and versatility; four natural products were prepared with
      differing stereochemistry and substitution patterns. Finally, this work allowed
      assignment of the absolute stereochemistry of 2,3,7-triepiaustraline and
      hyacinthacine A 7.

PMID- 18636742
TI  - Convergent and rapid assembly of substituted 2-pyridones through formation of N
      alkenyl alkynylamides followed by gold-catalyzed cycloisomerization.
AB  - A new method for the convergent and rapid assembly of substituted 2-pyridones was
      developed through the formation of N-alkenyl alkynylamides (amide-linked 1,5
      enynes) by N-acylation of imines with alkynoyl chlorides and the subsequent
      cationic Au(I)/PPh 3-catalyzed cycloisomerization.

PMID- 18636743
TI  - Interaction between the bound Mg.ATP and the Walker A serine residue in NBD2 of
      multidrug resistance-associated protein MRP1 plays a crucial role for the ATP
      dependent leukotriene C4 transport.
AB  - Structural analysis of human MRP1-NBD1 revealed that the Walker A S685 forms a
      hydrogen bond with the Walker B D792 and interacts with the Mg (2+) cofactor and
      the beta-phosphate of the bound Mg.ATP. We have found that substitution of the
      S685 with an amino acid that potentially prevents the formation of the hydrogen
      bond resulted in misfolding of the protein and significantly affect the ATP
      dependent leukotriene C4 (LTC4) transport. In this report we tested whether the
      corresponding substitution in NBD2 would also result in misfolding of the
      protein. In contrast to the NBD1 mutations, none of the mutations in NBD2,
      including S1334A, S1334C, S1334D, S1334H, S1334N, and S1334T, caused misfolding
      of the protein. However, elimination of the hydroxyl group at S1334 in mutations
      including S1334A, S1334C, S1334D, S1334H, and S1334N drastically reduced the ATP
      binding and the ATP-enhanced ADP trapping at the mutated NBD2. Due to this low
      efficient ATP binding at the mutated NBD2, the inhibitory effect of ATP on the
      LTC4 binding is significantly decreased. Furthermore, ATP bound to the mutated
      NBD2 cannot be efficiently hydrolyzed, leading to almost completely abolishing
      the ATP-dependent LTC4 transport. In contrast, S1334T mutation, which retained
      the hydroxyl group at this position, exerts higher LTC4 transport activity than
      the wild-type MRP1, indicating that the hydroxyl group at this position plays a
      crucial role for ATP binding/hydrolysis and ATP-dependent solute transport.

PMID- 18636745
TI  - Amino acid residues involved in membrane insertion and pore formation of
      Clostridium botulinum C2 toxin.
AB  - The actin-ADP-ribosylating Clostridium botulinum C2 toxin consists of the
      enzymatic component C2I and the binding component C2II. C2II forms heptameric
      channels involved in translocation of the enzymatic component into the target
      cell. On the basis of the heptameric toxin channel, we studied functional
      consequences of mutagenesis of amino acid residues probably lining the lumen of
      the toxin channel. Substitution of glutamate-399 of C2II with alanine blocked
      channel formation and cytotoxicity of the holotoxin. Although cytotoxicity and
      rounding up of cells by C2I were completely blocked by exchange of phenylalanine
      428 with alanine, the mutation increased potassium conductance caused by C2II in
      artificial membranes by about 2-3-fold over that of wild-type toxin. In contrast
      to its effects on single-channel potassium conductance in artificial membranes,
      the F428A mutation delayed the kinetics of pore formation in lipid vesicles and
      inhibited the activity of C2II in promoting (86)Rb (+) release from preloaded
      intact cells after pH shift of the medium. Moreover, F428A C2II exhibited delayed
      and diminished formation of C2II aggregates at low pH, indicating major changes
      of the biophysical properties of the toxin. The data indicate that phenylalanine
      428 of C2II plays a major role in conformational changes occurring during pore
      formation of the binding component of C2II.

PMID- 18636744
TI  - Identification of tyrosine 972 as a novel site of Jak2 tyrosine kinase
      phosphorylation and its role in Jak2 activation.
AB  - Jak2 is a 130 kDa tyrosine kinase that is important in a number of cellular
      signaling pathways. Its function is intrinsically regulated by the
      phosphorylation of a handful of its 49 tyrosines. Here, we report that tyrosine
      972 (Y972) is a novel site of Jak2 phosphorylation and, hence, autoregulation.
      Specifically, we found that Y972 is phosphorylated and confirmed that this
      residue resides on the surface of the protein. Using expression plasmids that
      expressed either wild-type Jak2 or a full-length Jak2 cDNA containing a single
      Y972F substitution mutation, we investigated the consequences of losing Y972
      phosphorylation on Jak2 function. We determined that the loss of Y972
      phosphorylation significantly reduced the levels of both Jak2 total tyrosine
      phosphorylation and phosphorylation of Y1007/Y1008. Additionally, Y972
      phosphorylation was shown to be important for maximal kinase function.
      Interestingly, in response to classical cytokine activation, the Jak2 Y972F
      mutant exhibited a moderately impaired level of activation when compared to the
      wild-type protein. However, when Jak2 was activated via a GPCR ligand, the
      ability of the Y972F mutant to be activated was completely lost, therefore
      suggesting a differential role of Y972 in Jak2 activation. Finally, we found that
      phosphorylation of Y972 enhances Jak2 kinase function via a mechanism that
      appears to stabilize the active conformation of the protein. Collectively, our
      results suggest that Y972 is a novel site of Jak2 phosphorylation and plays an
      important differential role in ligand-dependent Jak2 activation via a mechanism
      that involves stabilization of the Jak2 active conformation.

PMID- 18636746
TI  - The regulatory beta subunit of protein kinase CK2 contributes to the recognition
      of the substrate consensus sequence. A study with an eIF2 beta-derived peptide.
AB  - CK2 is a ubiquitous and pleiotropic Ser/Thr-specific protein kinase that
      phosphorylates more than 300 protein substrates at sites specified by an acidic
      consensus sequence in which positions n + 3 and n + 1 are particularly important.
      Recognition of substrates by CK2 is known to rely on basic residues located in
      the catalytic site of the alpha subunit which make electrostatic contacts with
      the negative charges in the substrate consensus sequence, thereby assuring
      optimal binding; the regulatory beta subunit is believed to play a protective and
      stabilizing role. We describe a biochemical and structural analysis of CK2
      mediated phosphorylation of a 22-mer synthetic peptide corresponding to the N
      terminal tail of the eukaryotic translation initiation factor eIF2beta. Results
      demonstrate that this peptide still displays phosphorylation features similar to
      full-length eIF2beta and the CK2 beta subunit also contributes to recognition of
      the protein substrate by establishing both polar and hydrophobic interactions
      with specificity determinants located downstream from the phosphoacceptor site.
      In particular, the N-terminal domain of the beta subunit appears to be of crucial
      importance for optimizing high-affinity phosphorylation of the eIF2beta peptide.
      This domain includes an acidic cluster whose electrostatic contacts with basic
      residues of the substrate attenuate intrasteric pseudosubstrate inhibition while
      strengthening substrate-kinase binding.

PMID- 18636747
TI  - Interacting targets of the farnesyl of transducin gamma-subunit.
AB  - G protein gamma-subunits are isoprenylated and carboxyl methylated at the C
      terminal cysteine residue, and the set of the posttranslational modifications is
      indispensable for the function of the photoreceptor G protein transducin
      (Talpha/Tbetagamma). To explore farnesyl-mediated molecular interactions, we
      investigated molecular targets of a Tbetagamma analogue that was engineered to
      have a photoreactive farnesyl analogue, (3-azidophenoxy)geranyl (POG), covalently
      bound to the C-terminal cysteine of Tgamma. POG-modified Tbetagamma was further
      subjected to modification by methylation at the C-terminal carboxyl group, which
      copies a complete set of the known posttranscriptional modifications of
      Tbetagamma. Photoaffinity labeling experiment with the photoreactive Tbetagamma
      analogue in its free form indicated that the POG moiety of Tgamma interacted with
      Tbeta. In the trimeric Talpha/Tbetagamma complex, the POG moiety was cross-linked
      with Talpha in addition to concurrent affinity labeling of Tbeta. When
      photoreactive Tbetagamma was reconstituted with Talpha and light-activated
      rhodopsin (Rh*) in rod outer segment (ROS) membranes, the POG moiety interacted
      with not only Talpha and Tbeta but also Rh* and membrane phospholipids. The cross
      linked phospholipid species was analyzed by ELISA employing a variety of lipid
      binding probes, which revealed phosphatidylethanolamine (PE) and
      phosphatidylserine (PS) as selective phospholipids for POG interaction in the ROS
      membranes. These results demonstrate that the modifying group of Tgamma plays an
      active role in protein-protein and protein-membrane interactions and suggest that
      the farnesyl-PE/PS interaction may support the efficient formation of the
      signaling ternary complex between transducin and Rh*.

PMID- 18636748
TI  - X-ray structure of papaya chitinase reveals the substrate binding mode of
      glycosyl hydrolase family 19 chitinases.
AB  - The crystal structure of a chitinase from Carica papaya has been solved by the
      molecular replacement method and is reported to a resolution of 1.5 A. This
      enzyme belongs to family 19 of the glycosyl hydrolases. Crystals have been
      obtained in the presence of N-acetyl- d-glucosamine (GlcNAc) in the
      crystallization solution and two well-defined GlcNAc molecules have been
      identified in the catalytic cleft of the enzyme, at subsites -2 and +1. These
      GlcNAc moieties bind to the protein via an extensive network of interactions
      which also involves many hydrogen bonds mediated by water molecules, underlying
      their role in the catalytic mechanism. A complex of the enzyme with a tetra
      GlcNAc molecule has been elaborated, using the experimental interactions observed
      for the bound GlcNAc saccharides. This model allows to define four major
      substrate interacting regions in the enzyme, comprising residues located around
      the catalytic Glu67 (His66 and Thr69), the short segment E89-R90 containing the
      second catalytic residue Glu89, the region 120-124 (residues Ser120, Trp121,
      Tyr123, and Asn124), and the alpha-helical segment 198-202 (residues Ile198,
      Asn199, Gly201, and Leu202). Water molecules from the crystal structure were
      introduced during the modeling procedure, allowing to pinpoint several additional
      residues involved in ligand binding that were not previously reported in studies
      of poly-GlcNAc/family 19 chitinase complexes. This work underlines the role
      played by water-mediated hydrogen bonding in substrate binding as well as in the
      catalytic mechanism of the GH family 19 chitinases. Finally, a new sequence motif
      for family 19 chitinases has been identified between residues Tyr111 and Tyr125.

PMID- 18636749
TI  - A small region in the angiotensin-converting enzyme distal ectodomain is required
      for cleavage-secretion of the protein at the plasma membrane.
AB  - Both germinal and somatic isoforms of ACE are type I ectoproteins expressed on
      the cell surface from where the enzymatically active ectodomains are released to
      circulation by a regulated cleavage-secretion process. Our previous studies have
      shown that ACE-secretase activity is regulated by the ACE distal ectodomain and
      not by sequences at or around the cleavage site. In the current study we have
      identified that the ACE residues encompassing 343 to 655 of the germinal form are
      needed for its cleavage-secretion. To narrow down this region further, we have
      examined the cleavage-secretion of ACE-CD4 chimeric proteins in mammalian cells
      and Pichia pastoris. These experiments identified five residues (HGEKL) in the
      ACE region of the chimeric proteins that were essential for their cleavage
      secretion. When the corresponding residues were substituted by alanine in native
      germinal and somatic ACE, the mutant proteins were not cleaved, although they
      were displayed on the cell surface and enzymatically active. These results
      demonstrated that a small region in the ectodomain of ACE is required for its
      cleavage at the juxtamembrane domain. This conclusion was further supported by
      our observation that secreted ACE inhibited cell-bound ACE cleavage-secretion,
      although the secreted form did not contain the cleavage site.

PMID- 18636750
TI  - Formation of the full SNARE complex eliminates interactions of its individual
      protein components with the Kv2.1 channel.
AB  - Previously, we have demonstrated physical and functional interactions of the
      voltage-gated potassium channel Kv2.1 with the plasma membrane protein components
      of the exocytotic SNARE complex, syntaxin 1A, and the t-SNARE, syntaxin 1A/SNAP
      25, complex. Importantly, the physical interaction of Kv2.1 with syntaxin was
      shown to be involved in the facilitation of secretion from PC12 cells, which was
      independent of potassium currents. Recently, we showed that also VAMP2, the
      vesicular SNARE, interacts physically and functionally with Kv2.1. Here, we first
      set out to test the interaction of the full SNARE, syntaxin/SNAP-25/VAMP2,
      complex with the channel. Using the interaction of VAMP2 with Kv2.1 in Xenopus
      oocytes as a probe, we showed that coexpression of the t-SNARE complex with VAMP2
      abolished the VAMP2 effect on channel inactivation and reduced the amount of
      VAMP2 that coprecipitated with Kv2.1. Further, in vitro pull down assays showed
      that the full SNARE complex failed to interact with Kv2.1 N- and C-termini in
      tandem, in contrast to the individual SNARE components. This suggests that the
      interactions of the SNARE components with Kv2.1 are abolished upon their
      recruitment into a full SNARE complex, which does not interact with the channel.
      Other important findings arising from the in vitro study are that the t-SNARE
      complex, in addition to syntaxin, interacts with a specific C-terminal channel
      domain, C1a, shown to mediate the facilitation of release by Kv2.1 and that the
      presence of Kv2.1 N-terminus has crucial contribution to these interactions.
      These findings provide important insights into the understanding of the complex
      molecular events involved in the novel phenomenon of secretion facilitation in
      neuroendocrine cells by Kv2.1.

PMID- 18636751
TI  - Kinetic studies of Cdk5/p25 kinase: phosphorylation of tau and complex inhibition
      by two prototype inhibitors.
AB  - Cdk5/p25 is a member of the family of cyclin-dependent, Ser/Thr kinases and is
      thought to play a causal role in Alzheimer's disease (AD) due to its ability to
      phosphorylate the protein tau, and thus promote the latter's aggregation into
      intraneuronal tangles. Given this, we and others are seeking inhibitors of
      cdk5/p25 as possible disease-modifying therapeutics for AD. In this paper, we
      first report the kinetic mechanism for the cdk5/p25-catalyzed phosphorylation of
      tau and histone H-1-derived peptide (H1P). These studies served as a necessary
      kinetic backdrop for investigations of the mechanism of inhibition by prototype
      inhibitors N4-(6-aminopyrimidin-4-yl)-sulfanilamide (APS) and 1-(5-cyclobutyl
      thiazol-2-yl)-3-isoquinolin-5-yl-urea (CTIU). We found that the cdk5/p25
      catalyzed phosphorylation of tau follows a rapid equilibrium, random kinetic
      mechanism, as evidenced by initial velocity analysis indicating sequential
      addition of tau and ATP, and studies of the mechanism of inhibition by substrate
      analogue AMP, product ADP, and analogues of peptide substrate H1P. Identical
      mechanistic conclusions were drawn when H1P was the phosphoryl acceptor.
      Subsequent studies of inhibition by APS and CTIU revealed that both compounds can
      bind to all four steady-state forms of the enzyme, to form the complexes E:I,
      E:I:tau, E:I:ATP, and E:I:tau:ATP. These results contrast with reported claims
      that APS and CTIU are competitive inhibitors of the binding of ATP.

PMID- 18636752
TI  - Contribution of individual amino acids to the 5S RNA binding activity of the
      Xenopus zinc finger protein p43.
AB  - Xenopus zinc finger protein p43 binds to 5S RNA in immature oocytes to form a 42S
      ribonucleoprotein storage particle. To determine the role of individual zinc
      fingers of the protein in this RNA binding activity, a series of deletion and
      substitution mutants of p43 were constructed. The effects of the various
      mutations on the RNA binding activity of p43 were determined using a quantitative
      equilibrium binding assay. The results indicate that zinc fingers 1 and 4 of p43
      are essential for the binding of the protein to 5S RNA. In the case of finger 1,
      four amino acids key to RNA binding are found on the same face of the alpha
      helix, while in the case of finger 4, two key residues are clustered at the start
      of the alpha-helix. The similarities and differences in the mechanisms by which
      fingers 1 and 4 of p43 interact with 5S RNA are compared to the interaction of
      the zinc fingers of Xenopus transcription factor IIIA with 5S RNA.

PMID- 18636753
TI  - Methylation of Xilf3 by Xprmt1b alters its DNA, but not RNA, binding activity.
AB  - Modification of proteins by methylation has emerged as a key regulatory mechanism
      in many cellular processes, including gene control. Eighty to ninety percent of
      the arginine methylation in the cell is performed by the protein arginine methyl
      transferase PRMT1. ILF3, a protein involved in gene regulation at several levels,
      has been shown to be a substrate and regulator of PRMT1 in mammals. Here we show
      that the Xenopus orthologue of ILF3 (Xilf3) is methylated in vivo, and, at least
      in vitro, this methylation is carried out by Xprmt1b. The in vitro methylation of
      Xilf3 inhibits its ability to bind to DNA while leaving RNA binding activity
      unaltered. Consistent with these activities having a role in vivo, the DNA
      binding activity of the Xilf3-containing CBTF complex and the transcription of
      its target gene, Xgata2, are both decreased by overexpression of Xprmt1b in
      embryos. However, in contrast to other RNA binding proteins, a changing degree of
      methylation does not alter the subcellular localization of Xilf3. Several other
      proteins involved in gene regulation can bind both RNA and DNA; these data
      demonstrate a mechanism by which such binding activities may be controlled
      independently.

PMID- 18636754
TI  - Functional and biophysical analysis of the C-terminus of the CGRP-receptor; a
      family B GPCR.
AB  - G-protein coupled receptors (GPCRs) typically have a functionally important C
      terminus which, in the largest subfamily (family A), includes a membrane-parallel
      eighth helix. Mutations of this region are associated with several diseases.
      There are few C-terminal studies on the family B GPCRs and no data supporting the
      existence of a similar eighth helix in this second major subfamily, which has
      little or no sequence homology to family A GPCRs. Here we show that the C
      terminus of a family B GPCR (CLR) has a disparate region from N400 to C436
      required for CGRP-mediated internalization, and a proximal region of twelve
      residues (from G388 to W399), in a similar position to the family A eighth helix,
      required for receptor localization at the cell surface. A combination of circular
      and linear dichroism, fluorescence and modified waterLOGSY NMR spectroscopy
      (SALMON) demonstrated that a peptide mimetic of this domain readily forms a
      membrane-parallel helix anchored to the liposome by an interfacial tryptophan
      residue. The study reveals two key functions held within the C-terminus of a
      family B GPCR and presents support for an eighth helical region with striking
      topological similarity to the nonhomologous family A receptor. This helix
      structure appears to be found in most other family B GPCRs.

PMID- 18636755
TI  - Structural defects play a major role in the acute lung toxicity of multiwall
      carbon nanotubes: physicochemical aspects.
AB  - Carbon nanotubes (CNT) have been reported to elicit toxic responses in vitro and
      in vivo, ascribed so far to metal contamination, CNT length, degree of oxidation,
      or extent of hydrophilicity. To examine how structural properties may modulate
      the toxicity of CNT, one preparation of multiwall CNT has been modified (i) by
      grinding (introducing structural defects) and subsequently heating either in a
      vacuum at 600 degrees C (causing reduction of oxygenated carbon functionalities
      and reduction of metallic oxides) or in an inert atmosphere at 2400 degrees C
      (causing elimination of metals and annealing of defects) and (ii) by heating at
      2400 degrees C in an inert atmosphere and subsequently grinding the thermally
      treated CNT (introducing defects in a metal-deprived carbon framework). The
      presence of framework and surface defects, metals, and oxygenated functionalities
      was monitored by means of a set of techniques, including micro-Raman
      spectroscopy, adsorption calorimetry, X-ray photoelectron spectroscopy,
      inductively coupled plasma mass spectrometry, and atomic emission spectroscopy.
      Contrary to traditional toxicants, such as asbestos, CNT may quench rather than
      generate oxygenated free radicals. The potential of the modified CNT to scavenge
      hydroxyl radicals was thus evaluated by means of electron spin resonance
      spectroscopy (spin trapping). The original ground material exhibited a scavenging
      activity toward hydroxyl radicals, which was eliminated by heating at 2400
      degrees C but restored upon grinding. This scavenging activity, related to the
      presence of defects, appears to go paired with the genotoxic and inflammatory
      potential of CNT reported in the companion paper. Thus, defects may be one of the
      major factors governing the toxic potential of CNT.

PMID- 18636756
TI  - Structural defects play a major role in the acute lung toxicity of multiwall
      carbon nanotubes: toxicological aspects.
AB  - Experimental studies indicate that carbon nanotubes (CNTs) have the potential to
      induce adverse pulmonary effects, including alveolitis, fibrosis, and
      genotoxicity in epithelial cells. Here, we explored the physicochemical
      determinants of these toxic responses with progressively and selectively modified
      CNTs: ground multiwall CNTs modified by heating at 600 degrees C (loss of
      oxygenated carbon functionalities and reduction of oxidized metals) or at 2400
      degrees C (annealing of structural defects and elimination of metals) and by
      grinding the material that had been heated at 2400 degrees C before (introduction
      of structural defects in a metal-deprived framework). The CNTs were administered
      intratracheally (2 mg/rat) to Wistar rats to evaluate the short-term response (3
      days) in bronchoalveolar lavage fluid (LDH, proteins, cellular infiltration, IL
      1beta, and TNF-alpha). The long-term (60 days) lung response was assessed
      biochemically by measuring the lung hydroxyproline content and histologically. In
      vitro experiments were also performed on rat lung epithelial cells to assess the
      genotoxic potential of the modified CNTs with the cytokinesis block micronucleus
      assay. The results show that the acute pulmonary toxicity and the genotoxicity of
      CNT were reduced upon heating but restored upon grinding, indicating that the
      intrinsic toxicity of CNT is mainly mediated by the presence of defective sites
      in their carbon framework.

PMID- 18636757
TI  - Rapid assembly of photosystem I monolayers on gold electrodes.
AB  - Photosystem I (PSI) has drawn widespread interest for use in biomimetically
      inspired energy conversion devices upon extracting it from plants or
      cyanobacteria and assembling it at surfaces. Here, we demonstrate that a
      critically dense monolayer of spinach-derived PSI must be formed on an electrode
      surface to achieve optimal photocurrents, and we introduce a new method for
      preparing these dense PSI monolayers that reduces the time required for assembly
      by approximately 80-fold in comparison to that for adsorption from solution. This
      method consists of applying a vacuum above the aqueous PSI solution during
      assembly to concentrate PSI and precipitate it into a thick layer onto the
      surface of various self-assembled monolayers or directly onto the electrode
      surface. Rinsing with water yields a dense monolayer of PSI that draws
      approximately 100 nA/cm2 of light-induced current from the gold electrode in the
      presence of appropriate mediators.

PMID- 18636758
TI  - Reductive glutaraldehydation of amine groups for identification of protein N
      termini.
AB  - In the present work, reductive alkylation of proteins and peptides with
      glutaraldehyde (reductive glutaraldehydation) is reported. The reaction is highly
      efficient and forms piperidine at the N-terminus as well as the side chain of
      lysine residues. The complete modification of protein amines was achieved by
      reductive glutaraldehydation in solution or in the gel in less than 15 min. The
      glutaraldehyde-modified peptides display an enhanced intensity in mass spectra
      and show higher retention time in reversed phase chromatography in comparison to
      unmodified peptides. Fragmentation of glutaraldehyde-modified proteins and
      peptides generates a1 fragment ions with enhanced intensity in MS/MS spectra.
      Thus, a method based on reductive glutaraldehydation and LC-MS/MS analysis has
      been developed to determine the N-terminal residue of proteins with free N
      termini.

PMID- 18636759
TI  - Simulating equilibrium surface forces in polymer solutions using a canonical grid
      method.
AB  - A new simulation method for nonuniform polymer solutions between planar surfaces
      at full chemical equilibrium is described. The technique uses a grid of points in
      a two-dimensional thermodynamic space, labeled by surface area and surface
      separations. Free energy differences between these points are determined via
      Bennett's optimized rates method in the canonical ensemble. Subsequently, loci of
      constant chemical potential are determined within the grid via simple numerical
      interpolation. In this way, a series of free energy versus separation curves are
      determined for a number of different chemical potentials. The method is applied
      to the case of hard sphere polymers between attractive surfaces, and its veracity
      is confirmed via comparisons with established alternative simulation techniques,
      namely, the grand canonical ensemble and isotension ensemble methods. The former
      method is shown to fail when the degree of polymerization is too large. An
      interesting interplay between repulsive steric interactions and attractive
      bridging forces occurs as the surface attraction and bulk monomer density are
      varied. This behavior is further explored using polymer density functional
      theory, which is shown to be in good agreement with the simulations. Our results
      are also discussed in light of recent self-consistent field calculations which
      correct the original deGennes results for infinitely long polymers. In
      particular, we look at the role of chain ends by investigating the behavior of
      ring polymers.

PMID- 18636760
TI  - Porphyrin J-aggregates stabilized by ferric myoglobin in neutral aqueous
      solution.
AB  - J-aggregates of a diacid form (H4TPPS2-) of 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphyrin (H2TPPS4-) were stabilized by binding with ferric
      myoglobin (metMb) in aqueous solution at neutral pH. The J-aggregates gradually
      dissociated to monomeric H2TPPS(4-). The average half-lifetime (t1/2) of the J
      aggregates in the presence of sufficient amounts of metMb was ca. 3 h in
      phosphate buffer at pH 7.0 and 25 degrees C. The stabilization of the J-aggregate
      by metMb is ascribed to encapsulation and fixation of an edge-to-edge structure
      of the J-aggregate by the relatively rigid protein molecules. The secondary
      structure of metMb was altered in some extent in the presence of an excess amount
      of the J-aggregates while no effect on denaturation of metMb was observed with
      the H2TPPS(4-) monomer or polyacrylate. The hydrophobic nature of the J-aggregate
      seems to play an important role for denaturation of metMb. The ability of
      denatured metMb to bind the azide anion was higher than that of natural metMb.
      The denaturation of metMb by the J-aggregates seems to induce surfacing of hemin
      leading to an entropy gain in coordination of the N3(-) anion to the iron(III)
      center.

PMID- 18636761
TI  - The binding orientation of a norindenoisoquinoline in the topoisomerase I-DNA
      cleavage complex is primarily governed by pi-pi stacking interactions.
AB  - High level ab initio quantum chemical studies have shown that the binding
      orientations of topoisomerase I (top1) inhibitors such as camptothecins and
      indenoisoquinolines are primarily governed by pi-pi stacking. However, a recently
      discovered norindenoisoquinoline antitumor compound was observed by X-ray
      crystallography to adopt a "flipped" orientation (relative to
      indenoisoquinolines), which facilitates the formation of a characteristic
      hydrogen bond with the Arg364 of top1 in its binding with the top1-DNA complex.
      This observation raises the possibility that hydrogen bonding between the
      norindenoisoquinoline nitrogen and the Arg364 side chain of top1 might be
      responsible for the "flip". It also brings into question whether pi-pi stacking,
      as opposed to hydrogen bonding, is primarily responsible for the binding
      orientations of indenoisoquinolines and norindenoisoquinolines. In this study,
      the forces responsible for the binding orientation of a norindenoisoquinoline in
      the DNA cleavage site were systematically investigated using MP2 methods. The
      theoretical calculation of the preferred binding orientation based solely on pi
      pi stacking was completely consistent with the actual orientation observed by X
      ray crystallography, indicating that the binding of the norindenoisoquinoline in
      the top1-DNA complex is mainly governed by pi-pi stacking forces and that the
      "flip" can occur independently from hydrogen bonding.

PMID- 18636762
TI  - Polymorphic packing and dynamics of biodegradable poly(3-hydroxypropionate).
AB  - The packing and dynamics of the beta-, gamma-, and delta-forms of poly(3
      hydroxypropionate) (P3HP), which represents the basic skeleton of bacterial
      poly(3-hydroxyalkanoate)s, were investigated by the variable-temperature FTIR and
      (13)C solid-state NMR measurements (SNMR). Under cooling, most of IR bands in the
      1500-750 cm(-1) region were noted to be distinctively blueshifted and enhanced,
      which should reflect the increased intermolecular interaction and depend on the
      chain packing of each crystal form. Furthermore, the temperature-dependent
      splitting of vibration were found to occur at the CH2 bending and rocking for the
      gamma-form, and at the CH2 bending and C-O-C stretching for the delta-form, while
      be absent for the beta-form. All the FTIR results indicate that the gamma-form
      has a stronger intermolecular interaction than the beta-form, although both adopt
      the all-trans conformation. The IR evidence measured during heating further
      reveal that the melting of the tightly packed gamma-form would pass through some
      mesophase, which lacks the regular packing but hold the long-range order along
      the chains. The delta-form was also found to be tightly packed, and contain at
      least and most possibly two chains in one unit cell. The CP/MAS (13)C SNMR
      spectrum of the delta-form was compared with those of the beta- and gamma-forms,
      and was well explained by combining the gamma-gauche and gamma-eclipsed effects.
      With considering possible differences in the magnetic dipole-dipole interaction
      among three crystal forms, the molecular mobilities of crystalline phases were
      estimated by the values of (13)C spin-lattice relaxation time to rank as delta <<
      gamma << beta. The diversified mobilities of three polymorphic crystalline
      phases, which is the key to crystalline-structure dependent biodegradability of
      P3HP, were discussed with considering the packing and conformation.

PMID- 18636763
TI  - Structural transformation of LiVOPO4 to Li3V2(PO4)3 with enhanced capacity.
AB  - In the present investigation, we report the transformation of alpha-LiVOPO 4 to
      alpha-Li 3V 2(PO 4) 3, leading to an enhancement of capacity. The alpha-LiVOPO 4
      sample was synthesized by a sol-gel method, followed by sintering at 550-650
      degrees C in a flow of 5% H 2/Ar. The structural transformation of a triclinic
      alpha-LiVOPO 4 structure to a monoclinic alpha-Li 3V 2(PO 4) 3 structure was
      observed at higher sintering temperatures (700-800 degrees C in a flow of 5% H
      2/Ar). The alpha-Li 3V 2(PO 4) 3 phase was characterized by X-ray diffraction,
      scanning electron microscopy, transmission electron microscopy, thermal
      gravimetric analysis, and X-ray absorption near edge spectrum (XANES) techniques.
      The valence shift of vanadium ions from +4 to +3 states was observed using in
      situ XANES experiments at V K-edge. The structural transformation is ascertained
      by the shape changes in pre-edge and near edge area of X-ray absorption spectrum.
      It was observed that the capacity was enhanced from 140 mAh/g to 164 mAh/g via
      structural transformation process of LiVOPO 4 to Li 3V 2(PO 4) 3.

PMID- 18636764
TI  - Assessing atomistic and coarse-grained force fields for protein-lipid
      interactions: the formidable challenge of an ionizable side chain in a membrane.
AB  - Ionizable amino acid side chains play important roles in membrane protein
      structure and function, including the activation of voltage-gated ion channels,
      where it has been previously suggested that charged side chains may move through
      the hydrocarbon core of the membrane. However, all-atom molecular dynamics
      simulations have demonstrated large free energy barriers for such lipid-exposed
      motions. These simulations have also revealed that the membrane will deform due
      to the presence of a charged side chain, leading to a complex solvation
      microenvironment for which empirical force fields were not specifically
      parametrized. We have tested the ability of the all-atom CHARMM, Drude
      polarizable CHARMM, and a recent implementation of a coarse-grained force field
      to measure the thermodynamics of arginine-membrane interactions as a function of
      protonation state. We have employed model systems to attempt to match
      experimental bulk partitioning and quantum mechanical interactions within the
      membrane and found that free energy profiles from nonpolarizable and polarizable
      CHARMM simulations are accurate to within 1-2 kcal/mol. In contrast, the coarse
      grained simulations failed to reproduce the same membrane deformations, exhibit
      interactions that are an order of magnitude too small, and thus, have incorrect
      free energy profiles. These results illustrate the need for careful
      parametrization of coarse-grained force fields and demonstrate the utility of
      atomistic molecular dynamics for providing quantitative thermodynamic and
      mechanistic analysis of protein-lipid interactions.

PMID- 18636765
TI  - Potential of mean force and pKa profile calculation for a lipid membrane-exposed
      arginine side chain.
AB  - The issue of ionizable protein side chains interacting with lipid membranes has
      been the focus of much attention since the proposal of the paddle model of
      voltage-gated ion channels, which suggested multiple arginine (Arg) side chains
      may move through the hydrocarbon core of a lipid membrane. Recent cell biology
      experiments have also been interpreted to suggest that these side chains would
      face only small free energy penalties to cross membranes, challenging a long
      standing view in membrane biophysics. Here, we employ side chain analog and
      transmembrane helix models to determine the free energy of an Arg side chain, as
      a function of protonation state, across a membrane. We observe high free energy
      barriers for both the charged and neutral states that would prohibit lipid
      exposed movement. The mechanisms for charged and neutral Arg transport are,
      however, very different, with the neutral state experiencing simple dehydration,
      whereas the charged state experiences a complex mechanism involving connections
      to the bilayer interfaces that deform the local membrane structure. We employ
      special methods to ensure sampling of these interfacial connections and decompose
      the free energy to shed light on the mechanisms. These deformations are found to
      preferentially stabilize the protonated form, such that the Arg side chain
      remains almost exclusively charged inside the membrane, with a pKa shift of
      <or=4.5 units. In contrast, the analog models are found to exaggerate the
      variations in energetics across the membrane and have larger pKa shifts. These
      results have implications for models of voltage gated ion channels, suggesting
      that although Arg side chains are ideally suited for carrying charge, the
      thermodynamics dictate that they must remain sequestered from the lipid bilayer
      environment.

PMID- 18636766
TI  - How electron localization function quantifies and pictures chemical changes in a
      solid: the B3-->B1 pressure induced phase transition in BeO.
AB  - Advantages of the analysis of the topology of the electron localization function
      (ELF) in the characterization of the chemical bonding in solids are illustrated
      in the study of the zinc blende --> rock salt transformation in BeO. The 4-fold
      to 6-fold coordination change is described as a two-step process: first, a
      catastrophic-like emergence of two new Be-O bonds reveals the onset of the rock
      salt structure, and second, the new interactions gradationally evolve to achieve
      the bonding network of the high-pressure phase. The increase in coordination, the
      volume collapse and the enhancement in the bulk modulus across the transition
      pathway are qualitatively and quantitatively traced back to the oxygen's valence
      shell. Although several ELF indexes point toward the expected greater bond
      polarity in the B3 than in the B1 structure, it can be concluded that there is no
      substantial modification in the nature of the crystal interactions induced by the
      phase transformation.

PMID- 18636767
TI  - Energetics and kinetics of primary charge separation in bacterial photosynthesis.
AB  - We report the results of molecular dynamics (MD) simulations and formal modeling
      of the free-energy surfaces and reaction rates of primary charge separation in
      the reaction center of Rhodobacter sphaeroides. Two simulation protocols were
      used to produce MD trajectories. Standard force-field potentials were employed in
      the first protocol. In the second protocol, the special pair was made polarizable
      to reproduce a high polarizability of its photoexcited state observed by Stark
      spectroscopy. The charge distribution between covalent and charge-transfer states
      of the special pair was dynamically adjusted during the simulation run. We found
      from both protocols that the breadth of electrostatic fluctuations of the
      protein/water environment far exceeds previous estimates, resulting in about 1.6
      eV reorganization energy of electron transfer in the first protocol and 2.5 eV in
      the second protocol. Most of these electrostatic fluctuations become dynamically
      frozen on the time scale of primary charge separation, resulting in much smaller
      solvation contributions to the activation barrier. While water dominates
      solvation thermodynamics on long observation times, protein emerges as the major
      thermal bath coupled to electron transfer on the picosecond time of the reaction.
      Marcus parabolas were obtained for the free-energy surfaces of electron transfer
      by using the first protocol, while a highly asymmetric surface was obtained in
      the second protocol. A nonergodic formulation of the diffusion-reaction electron
      transfer kinetics has allowed us to reproduce the experimental results for both
      the temperature dependence of the rate and the nonexponential decay of the
      population of the photoexcited special pair.

PMID- 18636768
TI  - Confinement-dependent below-gap state in PbS quantum dot films probed by
      continuous-wave photoinduced absorption.
AB  - We have measured continuous-wave (cw) photoinduced absorption (PA) spectra of PbS
      quantum dot (QD) films with four different sizes over a spectral range of 0.25
      0.5 eV at T=10 K. The PA spectrum shows a strong asymmetric IR absorption peak
      (IR-PA). Both the peak position and shape of this IR-PA indicate distinct
      confinement dependence. Combining with results of interband transitions and
      Stokes shift, we assign this IR-PA to a transition from a well-defined below-gap
      state to the second excitonic level (1P). By measuring the frequency dependence
      of this IR-PA, we estimate the lifetime of this below-gap state to be around
      several microseconds. Possible interpretations of the origin of this below-gap
      state are given. This transition could potentially be used to monitor
      photogenerated charge transfer in such QD systems.

PMID- 18636769
TI  - Understanding correlation effects for ion conduction in polymer electrolytes.
AB  - Polymer electrolytes typically exhibit diminished ionic conductivity due to the
      presence of correlation effects between the cations and anions. Microscopically,
      transient ionic aggregates, e.g., ion-pairs, ion-triplets, or higher order ionic
      clusters, engender ionic correlations. Employing all-atom simulation of a model
      polymer electrolyte comprising of poly(ethylene oxide) and lithium iodide, the
      ionic correlations are explored through construction of elementary functions
      between pairs of the ionic species that qualitatively explains the spatio
      temporal nature of these correlations. Furthermore, commencing from the exact
      Einstein-like equation describing the collective diffusivity of the ions in terms
      of the average diffusivity of the ions (i.e., the self-terms) and the
      correlations from distinct pairs of ions, several phenomenological parameters are
      introduced to keep track of the simplification procedure that finally boils down
      to the recently proposed phenomenological model by Stolwijk and Obeidi (SO)
      [Stolwijk, N. A.; Obeidi, S. Phys. Rev. Lett. 2004, 93, 125901]. The
      approximation parameters, which can be retrieved from simulations, point to the
      necessity of additional information in order to fully describe the correlation
      effects apart from the mere fraction of ion-pairs that apparently accounts for
      the correlations originating from only the nearest neighbor structural
      correlations. These parameters are close to, but are not exactly unity, as
      assumed in the SO model. Finally, as an application of the extended SO model, one
      is able to estimate the dynamics of the free and non-free ions as well as their
      fractions from the knowledge of the single particle diffusivities and the
      collective diffusivity of the ions.

PMID- 18636770
TI  - Modeling self-assembly processes driven by nonbonded interactions in soft
      materials.
AB  - This Centennial Feature Article provides an overview of research in the general
      area of self-assembly modeling, with particular emphasis on the self-assembly of
      molecules into soft nanoscale structures where the driving force for assembly is
      provided by nonbonded interactions (hydrogen bonds and electrostatics). The
      models have been developed at many different levels of theory, going all the way
      from simple analytical models of packing effects to atomistic descriptions using
      molecular dynamics methods. In between these limits are mean-field and coarse
      grained models, including models for DNA, peptides, and lipids that can be used
      to describe the assembly of hybrid (amphiphilic) materials. Several recent
      applications to specific systems are discussed, including the description of
      peptide amphiphile assembly to make cylindrical micelles, the assembly and
      melting of DNA hairpins, the use of DNA tethers to assemble nanoparticles into
      aggregates and crystalline structures, and the use of coarse-grained lipid models
      to make lamellar and high-curvature phases. These examples demonstrate the
      difficulties associated with brute force atomistic methods, and they also show
      the opportunities (but uncertainties and ambiguities) associated with simpler
      models such as coarse-grained models. The examples also demonstrate the
      usefulness of successful modeling methods in the design of new materials,
      including an understanding of the relationship between structure and function.

PMID- 18636771
TI  - Quaternary ammonium room-temperature ionic liquid including an oxygen atom in
      side chain/lithium salt binary electrolytes: ab initio molecular orbital
      calculations of interactions between ions.
AB  - Interactions of the lithium bis(trifluoromethylsulfonyl)amide (LiTFSA) complex
      with N, N-diethyl-N-methyl-N-(2-methoxyethyl) ammonium (DEME), 1-ethyl-3
      methylimidazolium (EMIM) cations, neutral diethylether (DEE), and the DEMETFSA
      complex were studied by ab initio molecular orbital calculations. An interaction
      energy potential calculated for the DEME cation with the LiTFSA complex has a
      minimum when the Li atom has contact with the oxygen atom of DEME cation, while
      potentials for the EMIM cation with the LiTFSA complex are always repulsive. The
      MP2/6-311G**//HF/6-311G** level interaction energy calculated for the DEME cation
      with the LiTFSA complex was -18.4 kcal/mol. The interaction energy for the
      neutral DEE with the LiTFSA complex was larger (-21.1 kcal/mol). The interaction
      energy for the DEMETFSA complex with LiTFSA complex is greater (-23.2 kcal/mol).
      The electrostatic and induction interactions are the major source of the
      attraction in the two systems. The substantial attraction between the DEME cation
      and the LiTFSA complex suggests that the interaction between the Li cation and
      the oxygen atom of DEME cation plays important roles in determining the mobility
      of the Li cation in DEME-based room temperature ionic liquids.

PMID- 18636772
TI  - Starmaker exhibits properties of an intrinsically disordered protein.
AB  - Fish otoliths composed of calcium carbonate and an organic matrix play a primary
      role in gravity sensing and the perception of sound. Starmaker (Stm) was the
      first protein found to be capable of influencing the process of biomineralization
      of otoliths. Stm dictates the shape, size, and selection of calcium carbonate
      polymorphs in a concentration-dependent manner. To facilitate exploration of the
      molecular basis of Stm function, we have developed and optimized a protocol for
      efficient expression and purification of the homogeneous nontagged Stm. The
      homogeneous nontagged Stm corresponds to its functional form, which is devoid of
      a signal peptide. A comprehensive biochemical and biophysical analysis of
      recombinant Stm, along with in silico examinations, indicate for the first time
      that Stm exhibits the properties of intrinsically disordered proteins. The
      functional significance of Stm having intrinsically disordered protein properties
      and its possible role in controlling the formation of otoliths is discussed.

PMID- 18636773
TI  - In situ FT-IR microscopic study on enzymatic treatment of poplar wood cross
      sections.
AB  - The feasibility of Fourier transform infrared (FT-IR) microscopy to monitor in
      situ the enzymatic degradation of wood was investigated. Cross-sections of poplar
      wood were treated with cellulase Onozuka RS within a custom-built fluidic cell.
      Light-optical micrographs and FT-IR spectra were acquired in situ from normal and
      tension wood fibers. Light-optical micrographs showed almost complete removal of
      the gelatinous (G) layer in tension wood. No structural and spectral changes were
      observed in the lignified cell walls. The accessibility of cellulose within the
      lignified cell wall was found to be the main limiting factor, whereas the
      depletion of the enzyme due to lignin adsorption could be ruled out. The fast,
      selective hydrolysis of the crystalline cellulose in the G-layer, even at room
      temperature, might be explained by the gel-like structure and the highly porous
      surface. Young plantation grown hardwood trees with a high proportion of G-fibers
      thus represent an interesting resource for bioconversion to fermentable sugars in
      the process to bioethanol.

PMID- 18636774
TI  - Enzymatic degradation of monolayer for poly(lactide) revealed by real-time atomic
      force microscopy: effects of stereochemical structure, molecular weight, and
      molecular branches on hydrolysis rates.
AB  - The influences of the stereochemical structure, the molecular weight, and the
      number of molecular branches for poly(lactide) (PLA) on enzymatic hydrolysis
      rates of PLA monolayers were studied by atomic force microscopy (AFM) and the
      Langmuir-Blodgett (LB) technique. Monolayers of six kinds of PLA with different
      molecular weights, stereochemical structure, and numbers of molecular branches
      were prepared by LB techniques and then characterized by AFM in air. The PLA
      molecules covered homogeneously with a silicon substrate and did not form
      lamellar crystals in the monolayer. We determined the initial hydrolysis rate of
      PLA monolayers in presence of proteinase K by volumetric analysis from the
      continuous AFM height images. The presence of D-lactyl unit reduced the
      hydrolysis rate of the monolayer. The hydrolysis rate for the linear PLLA samples
      increased with a decrease in the molecular weight. In contrast, the rates of
      erosion for branched PLLA monolayers were independent of the molecular weight of
      samples. The erosion rate of branched PLLA monolayers was found to be dependent
      on the average molecular weight of PLLA segment in branched molecules, not on the
      overall molecular weight of samples. From these results, furthermore, the
      hydrolysis mode of PLAs by proteinase K is discussed.

PMID- 18636775
TI  - Intelligent dual-responsive cellulose surfaces via surface-initiated ATRP.
AB  - Novel thermo-responsive cellulose (filter paper) surfaces of N
      isopropylacrylamide (NIPAAm) and pH-responsive cellulose surfaces of 4
      vinylpyridine (4VP) have been achieved via surface-initiated ATRP. Dual
      responsive (pH and temperature) cellulose surfaces were also obtained through the
      synthesis of block-copolymer brushes of PNIPAAm and P4VP. With changes in pH and
      temperature, these "intelligent" surfaces showed a reversible response to both
      individual triggers, as indicated by the changes in wettability from highly
      hydrophilic to highly hydrophobic observed by water contact angle measurements.
      Adjusting the composition of the grafted block-copolymer brushes allowed for
      further tuning of the wettability of these "intelligent" cellulose surfaces.

PMID- 18636776
TI  - Asymmetric synthesis of tetracyclic benzo[a]quinolizidine targets.
AB  - We report a novel, facile, and asymmetric approach for the synthesis of
      polycyclic benzo[ a]quinolizidine targets. In the formation of more
      functionalized derivatives, we have observed the generation of an iminium ether
      salt intermediate, formed during an unprecedented retro-Diels-Alder/ N
      acyliminium cyclization cascade. The iminium ether intermediate was isolated in
      good yield, characterized by X-ray crystallography, and subsequently applied as a
      synthetic building block.

PMID- 18636777
TI  - Characterization of polyketide metabolites from foliar endophytes of Picea
      glauca.
AB  - A collection of 250 foliar endophytes of Picea glauca (white spruce) yielded
      several isolates that produced metabolites toxic to Choristoneura fumiferana
      (spruce budworm). Three of these strains were selected for further study based on
      their ability to be cultured and produce secondary metabolites under laboratory
      conditions. The culture filtrate of each was extracted and analyzed by LC-MS and
      LC-NMR, and the major metabolites were isolated and characterized. Structures
      were elucidated by spectroscopic analyses including 2D NMR and HRMS and by
      comparison to literature data. In some cases the extract was methylated in order
      to facilitate separation, but the original natural structure was determined by
      comparing the NMR data of the isolated methylated product with that of the stop
      flow NMR of the underivatized extract (i.e., 2a, 2b, and 4). Two of these
      metabolites, 1 and 2a, are new structures, 3 and 4 are reported here for the
      first time as fungal metabolites, and 5- 10 as known fungal metabolites from
      other species. Tyrosol (10) was the only common metabolite found in all three
      extracts but did not account for the observed toxicity to C. fumiferana.

PMID- 18636778
TI  - Gold-catalyzed cycloisomerizations of enynes: a mechanistic perspective.

PMID- 18636779
TI  - Comparing guiding track requirements for myosin- and kinesin-powered molecular
      shuttles.
AB  - The design of nanoscale transport systems utilizing motor proteins as engines has
      advanced rapidly. Here, actin/myosin- and microtubule/kinesin-based molecular
      shuttles are compared with respect to their requirements for track designs. To
      this end, the trajectory persistence length of actin filaments gliding on myosin
      coated surfaces has been experimentally determined to be equal to 8.8 +/- 2
      microm. This measurement complements an earlier determination of the trajectory
      persistence length of microtubules gliding on kinesin-coated surfaces and enables
      a comparison of the accessible track designs for kinesin and myosin motor-powered
      systems. Despite the 200-fold smaller stiffness of actin filaments compared to
      that of microtubules, the dimensions of myosin tracks for actin filaments have to
      be quite similar to the dimensions of kinesin tracks for microtubules (radii
      larger than 200 nm and widths smaller than 0.9 microm compared to 600 nm and 19
      microm). The difference in gliding speed is shown to require additional
      consideration in the design of track modules.

PMID- 18636780
TI  - Ultralow loading Pt nanocatalysts prepared by atomic layer deposition on carbon
      aerogels.
AB  - Using atomic layer deposition (ALD), we show that Pt nanoparticles can be
      deposited on the inner surfaces of carbon aerogels (CA). The resultant Pt-loaded
      materials exhibit high catalytic activity for the oxidation of CO even at loading
      levels as low as approximately 0.05 mg Pt/cm2. We observe a conversion efficiency
      of nearly 100% in the 150-250 degrees C temperatures range, and the total
      conversion rate seems to be limited only by the thermal stability of the CA
      support in ambient oxygen. The ALD approach described here is universal in
      nature, and can be applied to the design of new catalytic materials for a variety
      of applications, including fuel cells, hydrogen storage, pollution control, green
      chemistry, and liquid fuel production.

PMID- 18636781
TI  - Theory and application of chain formation in break junctions.
AB  - We introduce a generic model of chain formation in break junctions by formulating
      criteria for the stability and producibility of suspended monatomic chains based
      on total energy arguments. Using ab initio calculations including spin
      polarization and spin-orbit coupling, we apply our model to the formation of
      monatomic 4d and 5d transition metal (TM) chains. We explain the physical origin
      of the experimentally observed general trend of increasing probability for the
      creation of long chains for late 5d TMs and suppressed chain formation for 4d
      TMs. We also clarify why the probability of chain elongation can be greatly
      enhanced by the presence of adsorbates in experiments.

PMID- 18636782
TI  - Compatibility assessment of CVD growth of carbon nanofibers on bulk CMOS devices.
AB  - We compare the level of deterioration in the basic functionality of individual
      transistors on ASIC chips fabricated in standard 130 nm bulk CMOS technology when
      subjected to three disparate CVD techniques with relatively low processing
      temperature to grow carbon nanostructures. We report that the growth technique
      with the lowest temperature has the least impact on the transistor behavior.

PMID- 18636783
TI  - Is the principle of a stable Heinrich ratio a myth? A multimethod analysis.
AB  - BACKGROUND: Safety improvements are sometimes based on the premise that
      introducing measures to combat minor or no-harm incidents proportionately reduces
      the incidence of major incidents involving harm. This is in line with the
      principle of the Heinrich ratio, which asserts that there is a relatively fixed
      ratio between the incidence of no-harm incidents, minor incidents and major
      incidents. This principle has been advocated as a means of targeting and
      evaluating new safety initiatives. RESEARCH METHODOLOGY: Both thought
      experimentation and analysis of empirical data were used to examine the
      plausibility of this principle. A descriptive statistical analysis was carried
      out using triangle plots to display the relative frequencies of the occurrence of
      safety incidents classified as minor, moderate or severe. FINDINGS: Thought
      experiments indicated that the principle of a fixed Heinrich ratio has a dubious
      logical foundation. Analysis of emergency department attendance and studies of
      medication errors demonstrated marked variation in the relative ratios of
      different outcomes. Triangle plots of UK road traffic accident data revealed a
      hitherto unrecognized systematic pattern of change that contradicts the principle
      of the Heinrich ratio. INTERPRETATION: This study of the principle of a fixed
      Heinrich ratio invalidates it: introducing measures to reduce the incidence of
      minor incidents will not inevitably reduce the incidence of major incidents pro
      rata. Any safety policies based on the assumption that the Heinrich ratio is true
      need to be rethought.

PMID- 18636785
TI  - Effects of stratification on data mining in the US Vaccine Adverse Event
      Reporting System (VAERS).
AB  - BACKGROUND: Vaccines are administered differentially according to age and sex,
      and disease patterns also vary among people of different age and sex groups.
      Estimates of disproportionality should be calculated based on comparisons of
      groups that have a similar likelihood of receiving similar vaccines and
      experiencing similar adverse events, to prevent false disproportionality from
      occurring. Stratified empirical Bayesian (EB) methods have been compared with
      crude, but not stratified, proportional reporting ratios (PRRs) in their
      performance on adverse event data. OBJECTIVES: (i) to implement stratification of
      PRR; (ii) to quantify and compare vaccine-event pairs that are highlighted by PRR
      and EB05 (the lower bound of the 90% CI of the EB geometric mean), for both crude
      and stratified; and (iii) to evaluate the effects of stratification by age and
      sex, in identifying adverse events that are accepted to be caused by vaccines.
      METHODS: We applied EB and PRR data mining methods to data from the US Vaccine
      Adverse Event Reporting System (VAERS). We stratified PRR and EB05 by age and
      sex. To study the effects of stratification, we compared the crude PRR and
      stratified PRR. We also assessed the crude EB05 and stratified EB05, and then
      compared the effects of stratification on EB05 and PRR. RESULTS: Stratification
      not only changed the number of vaccine-event pairs that were highlighted, but
      also changed which pairs were highlighted. There were 283 vaccine-event pairs
      that were highlighted by the crude EB05, but not the stratified; 12 that were
      highlighted by the stratified EB05, but not the crude; and 162 that were
      highlighted by both. Similarly, there were 701 vaccine-event pairs that were
      highlighted by the crude PRR, but not the stratified; 139 that were highlighted
      by the stratified PRR, but not the crude; and 895 that were highlighted by both.
      There were 1466 vaccine-event pairs in which the effect of stratification was
      different for EB05 and PRR. CONCLUSION: To our knowledge, this is the first
      published analysis using stratified PRRs. In this analysis of passive
      surveillance data, stratification revealed and reduced confounding in EB and PRR,
      and also unmasked some vaccine-event pairs that the crude values did not
      highlight. Stratification should be applied if confounding is suspected. By
      decreasing the total number of highlighted vaccine-event pairs, stratification is
      likely to increase efficiency and therefore might reduce workload.

PMID- 18636784
TI  - A benefit-risk assessment of benzbromarone in the treatment of gout. Was its
      withdrawal from the market in the best interest of patients?
AB  - Benzbromarone, a potent uricosuric drug, was introduced in the 1970s and was
      viewed as having few associated serious adverse reactions. It was registered in
      about 20 countries throughout Asia, South America and Europe. In 2003, the drug
      was withdrawn by Sanofi-Synthelabo, after reports of serious hepatotoxicity,
      although it is still marketed in several countries by other drug companies. The
      withdrawal has greatly limited its availability around the world, and increased
      difficulty in accessing it in other countries where it has never been
      available.The overall aim of this paper is to determine if the withdrawal of
      benzbromarone was in the best interests of gouty patients and to present a
      benefit-risk assessment of benzbromarone. To determine this, we examined (i) the
      clinical benefits associated with benzbromarone treatment and compared them with
      the success of alternative therapies such as allopurinol and probenecid,
      particularly in patients with renal impairment; (ii) the attribution of the
      reported cases of hepatotoxicity to treatment with benzbromarone; (iii) the
      incidence of hepatotoxicity possibly due to benzbromarone; (iv) adverse reactions
      to allopurinol and probenecid. From these analyses, we present recommendations on
      the use of benzbromarone.Large reductions in plasma urate concentrations in
      patients with hyperuricaemia are achieved with benzbromarone and most patients
      normalize their plasma urate. The half-life of benzbromarone is generally short
      (about 3 hours); however, a uricosuric metabolite, 6-hydroxybenzbromarone, has a
      much longer half-life (up to 30 hours) and is the major species responsible for
      the uricosuric activity of benzbromarone, although its metabolism by cytochrome
      P450 (CYP) 2C9 in the liver may vary between patients as a result of
      polymorphisms in this enzyme. It is effective in patients with moderate renal
      impairment. Standard dosages of benzbromarone (100 mg/day) tend to produce
      greater hypouricaemic effects than standard doses of allopourinol (300 mg/day) or
      probenecid (1000 mg/day).Adverse effects associated with benzbromarone are
      relatively infrequent, but potentially severe. Four cases of benzbromarone
      induced hepatotoxicity were identified from the literature. Eleven cases have
      been reported by Sanofi-Synthelabo, but details are not available in the public
      domain. Only one of the four published cases demonstrated a clear relationship
      between the drug and liver injury as demonstrated by rechallenge. The other three
      cases lacked incontrovertible evidence to support a diagnosis of benzbromarone
      induced hepatotoxicity. If all the reported cases are assumed to be due to
      benzbromarone, the estimated risk of hepatotoxicity in Europe was approximately 1
      in 17 000 patients but may be higher in Japan.Benzbromarone is also an inhibitor
      of CYP2C9 and so may be involved in drug interactions with drugs dependent on
      this enzyme for clearance, such as warfarin. Alternative drugs to benzbromarone
      have significant adverse reactions. Allopurinol is associated with rare life
      threatening hypersensitivity syndromes; the risk of these reactions is
      approximately 1 in 56 000. Rash occurs in approximately 2% of patients taking
      allopurinol and usually leads to cessation of prescription of the drug.
      Probenecid has also been associated with life-threatening reactions in a very
      small number of case reports, but it frequently interacts with many renally
      excreted drugs. Febuxostat is a new xanthine oxidoreductase inhibitor, which is
      still in clinical trials, but abnormal liver function is the most commonly
      reported adverse reaction.Even assuming a causal relationship between
      benzbromarone and hepatotoxicity in the identified cases, benefit-risk assessment
      based on total exposure to the drug does not support the decision by the drug
      company to withdraw benzbromarone from the market given the paucity of
      alternative options. It is likely that the risks of hepatotoxicity could be
      ameliorated by employing a graded dosage increase, together with regular
      monitoring of liver function. Determination of CYP2C9 status and consideration of
      potential interactions through inhibition of this enzyme should be considered.
      The case for wider and easier availability of benzbromarone for treating selected
      cases of gout is compelling, particularly for patients in whom allopurinol
      produces insufficient response or toxicity.We conclude that the withdrawal of
      benzbromarone was not in the best interest of patients with gout.

PMID- 18636786
TI  - Association between use of acid-suppressive drugs and risk of gastric cancer. A
      nested case-control study.
AB  - BACKGROUND: The risk of gastric cancer could be influenced by acid-related
      diseases or by the use of acid-suppressive drugs, such as histamine H(2) receptor
      antagonists and proton pump inhibitors (PPIs). OBJECTIVE: To assess the
      association between exposure to acid-suppressive drugs and the risk of gastric
      cancer. METHODS: A nested case-control study was conducted among people
      registered in the Quebec health insurance plan (Canada). Cases represented a
      random sample of subjects diagnosed with gastric cancer between 1995 and 2003 who
      were matched on age and sex to at least four controls (using incidence density
      sampling). The index date was the date of cancer diagnosis for the cases, which
      was the index date for the matched controls. The exposure definition in the 5
      years preceding the index date was based on the defined daily doses of acid
      suppressive drugs and categorized into quartiles. RESULTS: The study included
      1598 gastric cancer cases and 12 991 controls. The adjusted odds ratios for the
      association between exposure to acid-suppressive drugs and risk of gastric cancer
      were 1.47 (95% CI 1.23, 1.76), 1.32 (95% CI 1.10, 1.58), 1.48 (95% CI 1.24, 1.77)
      and 1.18 (95% CI 0.97, 1.44) for the first, second, third and fourth exposure
      quartiles, respectively. Similar results were obtained when use of H(2) receptor
      antagonists and PPIs were assessed separately (odds ratios for the association
      between PPIs and the risk of gastric cancer were slightly higher compared with
      H(2) receptor antagonists and risk of gastric cancer). CONCLUSIONS: A minor
      increase in the risk of gastric cancer was observed if exposure to either H(2)
      receptor antagonists or PPIs occurred within the past 5 years. However, this
      association is probably not causal since it is most likely due to confounding by
      indication.

PMID- 18636787
TI  - Associations between venous thromboembolism and antipsychotics. A study of the
      WHO database of adverse drug reactions.
AB  - BACKGROUND: Concern has been raised about the occurrence of venous
      thromboembolism (VTE) during treatment with antipsychotics. However, to date,
      clozapine is the only antipsychotic agent for which recurring evidence supports
      an association with VTE. Therefore, the aim of this study was to investigate the
      association between antipsychotic drugs, including clozapine and VTE. STUDY
      DESIGN AND METHODS: Data mining of the WHO database of adverse drug reactions
      (ADRs) using Bayesian statistics is in routine use for early alerting to possible
      ADRs. An information component measure was used to investigate the association
      between antipsychotic drugs and VTE reactions in the database. RESULTS: A total
      of 754 suspected cases of VTE related to treatment with antipsychotics had been
      reported. After excluding cases related to clozapine, 379 cases remained. A
      robust association was found for the second-generation antipsychotics group but
      not for the high-potency, first-generation antipsychotics group or the low
      potency first-generation antipsychotics group. The individual compounds with
      statistically significant associations were olanzapine, sertindole and
      zuclopenthixol. A time-dependent analysis showed that the associations were
      positive for these drugs in 2002, 2001 and 2003, respectively. Case analyses were
      undertaken after excluding ten suspected duplicate reports. Of the remaining 369
      cases, 91 cases were associated with olanzapine, 9 with zuclopenthixol and 6 with
      sertindole. CONCLUSIONS: VTE was more often reported with the antipsychotic drugs
      olanzapine, sertindole and zuclopenthixol than with other drugs in the WHO
      database. Further studies are warranted to explain this disproportional
      reporting. Since the associations found were based on incomplete clinical data,
      the results should be considered as preliminary and interpreted cautiously.

PMID- 18636788
TI  - Influence of chemical structure on hypersensitivity reactions induced by
      antiepileptic drugs: the role of the aromatic ring.
AB  - OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic'
      hypersensitivity reactions, i.e. the mechanism by which AEDs induce
      hypersensitivity is unknown. The aim of this study was to assess whether the
      presence of an aromatic ring as a commonality in chemical structures of AEDs can
      explain symptoms of hypersensitivity. METHODS: Between January 1985 and January
      2007, all adverse drug reactions (ADRs) reported to the Netherlands
      Pharmacovigilance Centre Lareb related to AEDs as suspected drugs were included
      in this study. ADRs were analysed using a case/non-case design. Cases were
      defined as those patients with ADRs involving symptoms of hypersensitivity. Non
      cases were patients with all other ADR reports. Symptoms of hypersensitivity were
      classified according to the Gell and Coombs classification (type I-IV) and the
      organ involved (e.g. cutaneous, hepatic). AEDs were classified as aromatic
      anticonvulsant if their chemical structure contained at least one aromatic ring.
      All other AEDs were classified as non-aromatic. We assessed the strength of the
      association between aromatic AEDs versus non-aromatic AEDs and reported
      hypersensitivity reactions with logistic regression analysis and expressed these
      as reporting odds ratios (RORs). RESULTS: In total, 303 cases of hypersensitivity
      associated with the use of AEDs were reported. Aromatic AEDs were suspected in
      64.4% of these reports versus 41.3% (574/1389) of the non-hypersensitivity
      reports. A significant ROR of 2.15 (95% CI 1.63, 2.82) was found for aromatic
      AEDs and all hypersensitivity reactions. Aromatic AEDs were significantly
      associated with immunoglobin E-mediated type I hypersensitivity reactions (ROR
      2.15; 95% CI 1.23, 3.78) and T-cell-mediated type IV reactions (ROR 6.06; 95% CI
      3.41, 10.75). Type II and III reactions did not show an association. Cutaneous
      symptoms represented 39.9% of the hypersensitivity-related ADRs. Aromatic AEDs
      were significantly associated with cutaneous hypersensitivity reactions (ROR
      5.81; 95% CI 3.38, 9.99). CONCLUSION: This study confirms that the presence of an
      aromatic ring as a common feature in chemical structures of AEDs partly explains
      apparent 'idiosyncratic' hypersensitivity reactions. Symptoms of hypersensitivity
      were reported twice as frequently with aromatic AEDs than with non-aromatic AEDs.
      Strong associations for aromatic AEDs versus non-aromatic AEDs were found for T
      cell-mediated (type IV) reactions, as well as for cutaneous reactions.

PMID- 18636789
TI  - Drug-related deaths: an analysis of the Italian spontaneous reporting database.
AB  - BACKGROUND: Adverse drug reactions (ADRs) represent a major public health
      concern, with death as the ultimate adverse drug outcome. Despite the relevance
      of this, the frequency of fatal ADRs (FADRs) is to a large extent unknown.
      Although spontaneous reporting data cannot give an exact estimate of the
      magnitude of drug-related mortality, it may highlight the importance and large
      dimensions of this public health problem. OBJECTIVE: To describe the types and
      pattern of reported FADRs by analysing data from the national spontaneous
      reporting system in Italy. METHODS: The Italian Medicines Agency (AIFA) runs a
      pharmacovigilance database where all the individual case safety reports (since
      January 2001) are stored. We selected and then analysed in detail all the case
      reports (to the end of December 2006) in which death was reported as the outcome.
      We included in the study only FADR case reports with a probable or possible
      causality assessment, according to the criteria established by the WHO. In line
      with the Italian reporting form, we divided FADR reports into two groups: (i)
      suspected ADRs that caused death; and (ii) suspected ADRs that contributed to
      death. RESULTS: In the AIFA database 38 507 suspected ADR case reports were
      collected, of which 641 (1.66%) had a fatal outcome. We analysed 450 case reports
      (1.17% of total reports), 159 (35.33%) of them causing the patient's death and
      291 (64.67%) contributing to death. The annual percentage of FADR reports
      followed a constant trend during the 6-year period. The majority of fatal reports
      (79%) were sent by hospital doctors. In total, 222 different drugs were suspected
      as causes of FADRs. 'Systemic anti-infective drugs' was the drug category
      associated with the highest percentage of FADRs (21.9%), followed by
      antineoplastic and immunomodulating agents (18.8%), and then by nervous system
      drugs (14.8%). Other drug categories involved in the fatal case reports were
      antithrombotic agents, NSAIDs and contrast media. CONCLUSIONS: The drugs most
      frequently involved in FADRs were drugs of wide usage with a narrow therapeutic
      range or those that caused serious skin or systemic allergic reactions.
      Ceftriaxone, ticlopidine and nimesulide were associated with the highest number
      of fatal case reports; the related FADRs were already known and recognized for
      each of these drugs. We highlight some cases reflecting probable inappropriate
      drug use by Italian physicians. This suggests a need for continued clinical
      pharmacology training and that many FADRs might be preventable through better
      medical and prescribing practice.

PMID- 18636790
TI  - Safety of efalizumab therapy in patients with moderate to severe psoriasis: an
      open-label extension of a phase IIIb trial.
AB  - BACKGROUND: Psoriasis is a chronic autoimmune disease characterized by
      infiltration of the dermis and epidermis by activated T cells and the
      hyperproliferation and abnormal differentiation of keratinocytes. It is a life
      long disease with alternating periods of remission and recurrence. Efalizumab is
      a humanized, recombinant, T-cell targeting monoclonal antibody, approved for use
      in adults with chronic moderate to severe plaque psoriasis. OBJECTIVE: To assess
      the safety of continued or newly initiated treatment with efalizumab for up to 48
      weeks in patients with psoriasis who were treated previously with efalizumab or
      placebo. METHODS: This study was an open-label, 48-week extension of a previously
      published 12-week, randomized, double-blind, parallel-group, placebo-controlled,
      multicentre, phase IIIb study, carried out in the US and Canada between 24
      October 2002 and 2 July 2004. Patients were followed and treated at the study
      clinic in an outpatient setting and also were trained to self-administer the drug
      at home. Patients comprising individuals with chronic moderate to severe plaque
      psoriasis who had completed the 12-week, placebo-controlled segment of the study
      were eligible for enrolment in the extension phase. Of the 686 patients enrolled
      in the study, 636 (92.7%) enrolled in the open-label extension of the study, 418
      of whom had received 12 weeks of efalizumab therapy and 218 of whom had received
      12 weeks of placebo. All patients entering the open-label phase of the study
      received efalizumab 1 mg/kg/wk for an additional 48 weeks, for a maximum exposure
      of up to 60 weeks. Safety was evaluated by an assessment of adverse events,
      including infections and serious adverse events. RESULTS: The rate of withdrawal
      due to adverse events remained low throughout the trial, ranging from 1.2% to
      6.6% during the 12-week segments of the open-label extension phase of the trial.
      The incidence of adverse events decreased with increased exposure to efalizumab;
      the incidence during the initial 12 weeks of exposure to efalizumab was 79.0%
      compared with 72.9% for patients exposed to placebo. Patients treated with
      efalizumab for 13-24 weeks, 25-36 weeks, 37-48 weeks and 49-60 weeks experienced
      adverse events at an incidence of 66.8%, 54.3%, 49.6% and 48.5%, respectively.
      The incidence of serious adverse events ranged from 1.6% to 3.5% during the 12
      week segments of efalizumab therapy, compared with an incidence of 3.4% for
      placebo-treated patients. The incidence of infection ranged from 9.9% to 14.7%
      during the 12-week segments of efalizumab therapy, compared with an incidence of
      19.1% for placebo-treated patients. Malignancies were reported with an incidence
      of </=1.0% for efalizumab-treated patients during any 12-week segment compared
      with 0.4% for the 12-week placebo-treated patients. Of the 15 malignancies
      reported for efalizumab-treated patients, 13 were basal cell (n = 4) or squamous
      cell (n = 9) carcinomas. CONCLUSIONS: These results support the short-term safety
      profile demonstrated for efalizumab over a longer-term therapy period of up to 60
      weeks.

PMID- 18636792
TI  - Assessing the risks of persistent organic pollutants to top predators: a review
      of approaches.
AB  - Accurate risk assessment of secondary poisoning by persistent organic pollutants
      (POPs) in top predators is possible but requires multidisciplinary input from
      wildlife ecology, ecotoxicology, and analytical chemistry. Because of the
      transfer of POPs up the food chain, traditional approaches to exposure assessment
      based on POPs in abiotic compartments or organisms low in the food chain can make
      the assessment of risk to top predators complicated. For more direct, accurate,
      and site-specific methods of assessing the risks of secondary poisoning of top
      predator by POPs, we classify 2 main approaches: diet based and tissue based.
      Exposure assessment via the diet-based approach requires samples of the
      predator's diet and measured concentrations in the prey items, realistic
      estimates of dietary composition, and ingestion rates. The even more direct,
      tissue-based approach uses measured POP concentrations in tissues of top
      predators to determine internal exposure coupled with tissue-based effect
      concentrations (or biological responses measured via biomarkers) to determine
      risk. The advantage of these methods is that uncertain estimates of POPs transfer
      to top predators from lower trophic levels are avoided. In practice, the
      availability of dose-response data and internal exposure-response relationships
      for POPs in top predators is limited, so these may have to be extrapolated from
      surrogate species. In this paper we illustrate and evaluate the potential of diet
      based and tissue-based risk assessment approaches with case studies and
      demonstrate that appropriate methodologies significantly reduce the uncertainty
      in risk assessments of POPs.

PMID- 18636793
TI  - Allantoin as a marker of oxidative stress in human erythrocytes.
AB  - BACKGROUND: Uric acid is the final product of purine metabolism in humans. It was
      determined that this compound has important antioxidative properties and it may
      be oxidized to allantoin by various reactive oxygen species. Therefore, the
      measurement of allantoin may be useful for the determination of oxidative stress
      in humans. METHODS: We measured allantoin and uric acid in human plasma and
      erythrocytes obtained from patients with chronic renal failure before
      hemodialysis (n=30) and blood donors (n=30). We used a method based on selective
      isolation of allantoin from deproteinized plasma and erythrocyte lysate samples
      on AG 1-X8 resin and its derivatization to glyoxylate-2, 4
      dinitrophenylhydrazone. Separation of glyoxylate-2, 4-dinitrophenylhydrazone from
      interfering substances was achieved on reversed phase HPLC with gradient elution
      and UV/VIS detection at 360 nm. Uric acid was determined by reversed phase HPLC
      with UV/VIS detection at 292 nm. RESULTS: We found significant differences in
      allantoin and uric acid concentration between the patients with chronic renal
      failure and the control group both in plasma (20.5+/-6.5 micromol/L and 323.9+/
      62.9 micromol/L vs. 2.1+/-1.1 micromol/L and 270.1+/-62.3 micromol/L, p<0.05) and
      erythrocytes [82.8+/-39.1 nmol/g hemoglobin (Hb) and 110.7+/-28.8 nmol/g Hb vs.
      20.1+/-6.1 nmol/g Hb and 82.1+/-23.7 nmol/g Hb, p<0.05]. CONCLUSIONS: Significant
      higher levels of allantoin in both plasma and erythrocytes of patients with
      chronic renal failure indicate that allantoin may be used as a good marker of
      oxidative stress.

PMID- 18636794
TI  - Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian
      women.
AB  - BACKGROUND: Hyperhomocysteinemia and B-vitamin deficiency are associated with
      recurrent abortion. Recent studies have not investigated functional markers of
      vitamin B12 deficiency, such as methylmalonic acid. METHODS: A total of 43
      consecutive Syrian women with unexplained recurrent abortion and 32 pregnant
      controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic
      acid and plasma homocysteine were determined. RESULTS: Vitamin B12 was
      significantly decreased in patients with recurrent abortion compared to controls
      (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin
      B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in
      aborters in comparison to controls (8.3 vs. 7.1 micromol/L, p=0.093). Folate and
      methylmalonic acid did not differ significantly between the study groups. A
      highly significant correlation between homocysteine and methylmalonic acid and
      vitamin B12 was observed only in patients but not in controls (p<0.001 and
      p=0.002, respectively). In the logistic regression model, only serum vitamin B12
      emerged with a significant odds ratio. CONCLUSIONS: The results confirm low serum
      vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not
      support that functional vitamin B12 plays a role in this group. This unexpected
      result might be due to a decrease of the metabolically inert vitamin B12 fraction
      (holohaptocorrin) or confounding factors. Further studies are necessary to
      investigate the role of vitamin B12 deficiency in recurrent abortion.

PMID- 18636795
TI  - Influence of acute physical exercise on emerging muscular biomarkers.
AB  - BACKGROUND: Although there is comprehensive information on traditional biomarkers
      of muscle and cardiac damage following exercise, less is known on the kinetics of
      innovative markers, including ischemia modified albumin (IMA), glycogen
      phosphorylase isoenzyme BB (GPBB), carbonic anhydrase III (CAIII) and heart-type
      fatty acid-binding protein (H-FABP) in athletes performing a sub-maximal
      exercise. METHODS: A total of 10 healthy trained Caucasian males performed a 21
      km run. Blood samples were collected before the run, immediately after (post), 3,
      6 and 24 h thereafter. Cardiac troponin I (cTnI), myoglobin, creatine kinase
      isoenzyme MB (CK-MB), GPBB, CAIII and H-FABP were assayed using a new diagnostic
      system based on protein biochip array technology. IMA was measured by a
      commercial colorimetric assay on a Roche Modular system P. RESULTS: Significant
      variations by one-way analysis of variance were observed for CK-MB (p=0.013),
      myoglobin (p<0.001), GPBB (p=0.029), H-FABP (p<0.001), CAIII (p=0.006), but not
      for cTnI (p=1.00) and IMA (p=0.881). In particular, values of all the biomarkers
      tested, but cTnI and IMA, increased significantly immediately after the run. GPBB
      and H-FABP values returned to baseline 6 and 3 h thereafter, those of CAIII, CK
      MB and myoglobin remained significantly elevated from the pre-run value up to 24
      h after the run. The major variation over pre-run values was recorded for
      myoglobin (nearly 4-fold increment), whereas CAIII, CK-MB, GPBB and H-FABP
      increased by 2.9-, 1.8-, 1.4- and 1.2-fold, respectively. CONCLUSIONS: We
      conclude that a sub-maximal aerobic exercise influences the concentration of
      several markers of muscle damage. Except for IMA, not one of the emerging
      biomarkers tested can be safely used to rule out myocardial damage as well as
      cardiospecific troponins in patients who had undergone recent physical activity.

PMID- 18636796
TI  - Cementum and periodontal ligament-like tissue formation induced using
      bioengineered dentin.
AB  - Stem cell-mediated root regeneration offers opportunities to regenerate a bio
      root and its associated periodontal tissues to restore tooth loss. Periodontal
      ligament (PDL) and cementum complex and dentin pulp complex have been tissue
      engineered using human dental pulp stem cells and PDL stem cells, respectively.
      The aim of this study was to explore whether dentin formation could be induced
      using an inductive substrate and whether bioengineered dentin could induce
      cementum and PDL formation. First, dentin was bioengineered from tooth papillae
      of Sprague-Dawley (SD) rats with an inductive substrate, and its phenotype was
      characterized; then primarily cultured human PDL cells were seeded on the surface
      of dentin and transplanted under the skin of immunocompromised mice.
      Histological, immunohistochemical, and scanning electronic microscopy
      examinations results showed that bioengineered dentin could induce cementogenesis
      and PDL formation, and condense PDL arranged perpendicularly on the dentin
      surface via a layer of cementum-like tissue. The results indicated that tissue
      engineered dentin could be induced using an inductive substrate and could be used
      as a further substrate for cementum and PDL tissue engineering.

PMID- 18636940
TI  - Interstitial fluid flow intensity modulates endothelial sprouting in restricted
      Src-activated cell clusters during capillary morphogenesis.
AB  - Development of tissues in vitro with dimensions larger than 150 to 200 microm
      requires the presence of a functional vascular network. Therefore, we have
      studied capillary morphogenesis under controlled biological and biophysical
      conditions with the aim of promoting vascular structures in tissue constructs. We
      and others have previously demonstrated that physiological values of interstitial
      fluid flow normal to an endothelial monolayer in combination with vascular
      endothelial growth factor play a critical role during capillary morphogenesis by
      promoting cell sprouting. In the present work, we studied the effect that a range
      of interstitial flow velocities (0-50 microm/min) has in promoting the amount,
      length, and branching of developing sprouts during capillary morphogenesis. The
      number of capillary-like structures developed from human umbilical vein
      endothelial cell monolayers across the interstitial flow values tested was not
      significantly affected. Instead, the length and branching degree of the sprouts
      presented a significant maximum at flow velocities of 10 to 20 microm/min. More
      over, at these same flow values, the phosphorylation level of Src also showed its
      peak. We discovered that capillary morphogenesis is restricted to patches of Src
      activated cells (phosphorylated Src (pSrc)) at the monolayer, suggesting that the
      transduction pathway in charge of sensing the mechanical stimulus induced by flow
      is promoting predetermined mechanically sensitive areas (pSrc) to undergo
      capillary morphogenesis

PMID- 18636941
TI  - Distinct intervertebral disc cell populations adopt similar phenotypes in three
      dimensional culture.
AB  - Tissue engineering strategies have the potential to improve upon current
      techniques for intervertebral disc repair. However, determining a suitable
      biomaterial scaffold for disc regeneration is difficult due to the complex
      fibrocartilaginous structure of the tissue. In this study, cells isolated from
      three distinct regions of the intervertebral disc, the outer and inner annulus
      fibrosus and nucleus pulposus, were expanded and seeded on resorbable polyester
      fiber meshes and encapsulated in calcium crosslinked alginate hydrogels, both
      chosen to approximate the native tissue architecture. Three-dimensional (3D)
      constructs were cultured for 14 days in vitro and evaluated histologically and
      quantitatively for gene expression and production of types I and II collagen and
      proteoglycans. During monolayer expansion, the cell populations maintained their
      distinct phenotypic morphology and gene expression profiles. However, after 14
      days in 3D culture, there were no significant differences in morphology, gene
      expression, or protein production between all three cell populations grown in
      either alginate or polyester fiber meshes. The results of this study indicate
      that the culture environment may have a greater impact on cellular behavior than
      the intrinsic origin of the cells, and suggest that only a single-cell type may
      be required for intervertebral disc regenerative therapies.

PMID- 18636942
TI  - A novel copolymer poly(lactide-co-beta-malic acid) with extended carboxyl arms
      offering better cell affinity and hemacompatibility for blood vessel engineering.
AB  - Despite their increasing uses for cardiovascular and cerebrovascular tissue
      engineering, synthetic polymeric conduits still have their limitations in
      clinical applications, particularly in small vessels, mainly due to the thrombus
      formation. Seeding the synthetic scaffolds with endothelial cells (ECs) will
      potentially solve this problem, but this endothelialization approach demands
      synthetic materials with better hemacompatibility and cell affinity. To improve
      the currently used materials and screen for better surface properties, we
      synthesized copolymer of poly(lactide-co-beta-malic acid) (PLMA), and its
      derivatives with pendant hydroxyl arms (PLMAHE) or extended carboxyl arms (PLMA
      ECA). We analyzed their physical and chemical properties, their hydrophilicity,
      and their degradation in physiological conditions. More importantly, their blood
      compatibility was investigated by the measurements of prothrombin time, activated
      partial thromboplastin time, and interaction with platelets; their cell affinity
      and cell growth potentials were observed using the human umbilical vein EC
      cultures. Results from these experiments showed that the copolymer with the
      carboxyl arms attracted little platelets, and exhibited better cell affinity and
      supported the cell proliferation, thus demonstrating the potential usefulness of
      PLMA-ECA for tissue engineering. We speculate that this novel material will offer
      new opportunities for the design of better vascular-engineered scaffolds owing to
      its improved biological and chemical properties.

PMID- 18636943
TI  - Maxillofacial-derived stem cells regenerate critical mandibular bone defect.
AB  - Stem cell-based bone tissue regeneration in the maxillofacial complex is a
      clinical necessity. Genetic engineering of mesenchymal stem cells (MSCs) to
      follow specific differentiation pathways may enhance the ability of these cells
      to regenerate and increase their clinical relevance. MSCs isolated from
      maxillofacial bone marrow (BM) are good candidates for tissue regeneration at
      sites of damage to the maxillofacial complex. In this study, we hypothesized that
      MSCs isolated from the maxillofacial complex can be engineered to overexpress the
      bone morphogenetic protein-2 gene and induce bone tissue regeneration in vivo. To
      demonstrate that the cells isolated from the maxillofacial complex were indeed
      MSCs, we performed a flow cytometry analysis, which revealed a high expression of
      mesenchyme-related markers and an absence of non-mesenchyme-related markers. In
      vitro, the MSCs were able to differentiate into osteogenic, chondrogenic, and
      adipogenic lineages. Gene delivery of the osteogenic gene BMP2 via an adenoviral
      vector revealed high expression levels of BMP2 protein that induced osteogenic
      differentiation of these cells in vitro and induced bone formation in an ectopic
      site in vivo. In addition, implantation of genetically engineered maxillofacial
      BM-derived MSCs into a mandibular defect led to regeneration of tissue at the
      site of the defect; this was confirmed by performing micro-computed tomography
      analysis. Histological analysis of the mandibles revealed osteogenic
      differentiation of implanted cells as well as bone tissue regeneration. We
      conclude that maxillofacial BM-derived MSCs can be genetically engineered to
      induce bone tissue regeneration in the maxillofacial complex and that this
      finding may be clinically relevant.

PMID- 18636944
TI  - In vitro generation of a scaffold-free tissue-engineered construct (TEC) derived
      from human synovial mesenchymal stem cells: biological and mechanical properties
      and further chondrogenic potential.
AB  - The purpose of this study was to characterize a tissue-engineered construct (TEC)
      generated with human synovial mesenchymal stem cells (MSCs). MSCs were cultured
      in medium with ascorbic acid 2-phosphate (Asc-2P) and were subsequently detached
      from the substratum. The detached cell/matrix complex spontaneously contracted to
      develop a basic TEC. The volume of the TEC assessed by varying initial cell
      density showed that it was proportional to initial cell densities up to 4 x 10(5)
      cells/cm(2). Assessment of the mechanical properties of TEC using a custom device
      showed that the load at failure and stiffness of the constructs significantly
      increased with time of culture in the presence of Asc-2P, while in the absence of
      Asc-2P, the constructs were mechanically weak. Thus, the basic TEC possesses
      sufficiently self-supporting mechanical properties in spite of not containing
      artificial scaffolding. TEC further cultured in chondrogenic media exhibited
      positive alcian blue staining with elevated expression of chondrogenic marker
      genes. Based on these findings, such human TEC may be a promising method to
      promote cartilage repair for future clinical application.

PMID- 18636945
TI  - Perfusion cell seeding and cultivation induce the assembly of thick and
      functional hepatocellular tissue-like construct.
AB  - Developing advanced technologies for encouraging the ex vivo assembly of
      functional hepatic tissue for implantation into the human body or for in vitro
      drug testing is one of the challenging tasks facing tissue engineers. In the
      present study, we utilized a perfusion bioreactor system equipped with a novel
      flow-distributing mesh for online cell seeding into macroporous alginate
      scaffolds and cultivation of multiple constructs of the C3A human hepatocyte cell
      line. Optimization of the medium flow rate (100 mL/min) and perfusion duration
      (12 h) yielded cell constructs with high cell seeding efficiency (98% of the
      input cells) and cell distribution throughout the entire scaffold. Further, we
      show that interstitial medium flow enabled uniform cell delivery into 35
      constructs lined across the bioreactor cross section. Perfusion-cultivated cell
      constructs revealed much greater rates of cell proliferation, albumin-specific
      secretion, and gene expression of the phase I enzyme, CYP3A4, and phase II
      enzyme, UGT2B7, than did static-cultivated constructs. Most impressive was the 50
      fold increase in CYP3A4 expression of the perfused cell constructs as compared to
      the level in static-cultivated cell constructs. We thus believe that the hepatic
      tissue constructs developed herein may be used in drug discovery programs for
      elucidating drug metabolism and toxicity profiles and for treating failing
      livers.

PMID- 18636946
TI  - Fetal abdominal wall repair with a collagen biomatrix in an experimental sheep
      model for gastroschisis.
AB  - We evaluated the regeneration of the abdominal wall using a dual-layer collagen
      biomatrix, and the protective effect on the bowel of fetal abdominal wall repair
      in a fetal sheep model for gastroschisis. In 14 fetal lambs, the abdominal wall
      was opened at 79 days' gestation, creating a gastroschisis. In group 1, the
      gastroschisis was left uncovered. In group 2, the bowel was repositioned, and the
      defect was closed by suturing a collagen biomatrix into the abdominal wall. A
      cesarean section was performed at 140 days' gestation, and macroscopic and
      histological evaluation was performed. In the five lambs with a gastroschisis,
      the eviscerated part of the bowel was coalescent, showed extensive adhesions, and
      was covered by fibrous peel. In group 2, the abdominal wall had closed, with a
      firm connection to the native abdominal wall. The biomatrix was largely degraded
      and replaced by connective tissue with collagen and fibroblasts,
      neovascularisation, and scattered muscle cells. Minor or no adhesions of the
      bowel and no peel formation were observed. Abdominal wall tissue replacement
      using a collagen biomatrix was feasible in fetal lambs, resulting in a closed
      abdominal wall at birth. Immediate closure of the gastroschisis strongly
      diminished or prevented bowel adhesions and peel formation.

PMID- 18636947
TI  - Persistence of collagen type II synthesis and secretion in rapidly proliferating
      human articular chondrocytes in vitro.
AB  - Articular chondrocytes (AC) expanded in vitro for tissue engineering rapidly turn
      off collagen type II (COL2) synthesis. We wanted to inhibit this process
      sufficiently to obtain therapeutically useful numbers of AC without losing COL2
      synthesis. To this end, AC were expanded on their own extracellular matrix (ECM)
      in structures designated chondrocytes in autologous ECM (CA-ECM). Here, AC
      maintained a rounded shape and proliferated rapidly. After 13-15 days in culture,
      40 x 10(6) cells (median) could be obtained from a cartilage biopsy. Real-time RT
      PCR showed a reduced, but persistent, production of COL2A1 mRNA at this time.
      Flow cytometry showed high levels of intracellular COL2, and immunogold electron
      microscopy showed high density of well-organized COL2 fibrils in newly
      synthesized ECM. Interestingly, high levels of COL1A1 mRNA and intracellular
      protein were detected, but no COL1 was found in the ECM. The slow loss of COL2A1
      mRNA was paralleled by a loss of the COL2 regulating transcription factor SOX9
      mRNA. Chromatin immunoprecipitation assays could not identify epigenetic histone
      modifications that would explain the observed changes in COL2 synthesis. Thus,
      the CA-ECM strategy allows AC to proliferate to clinically useful numbers while
      maintaining COL2 synthesis and secretion. This strategy may improve tissue
      engineering of joint surfaces.

PMID- 18636948
TI  - Delivery of basic fibroblast growth factor from gelatin microsphere scaffold for
      the growth of human umbilical vein endothelial cells.
AB  - One of the major obstacles for engineering large tissue or organs such as the
      liver in vitro is the insufficient supply of nutrients and oxygen to the cells
      growing inside the scaffold, which reduces cell viability significantly.
      Therefore, vascularization of the scaffolding system is necessary for successful
      engineering of such tissues. In this study, we investigated the use of gelatin
      microsphere as scaffold to culture human umbilical vein endothelial cells, which
      is considered to be the basis and premise for the formation of blood vessels. The
      gelatin microspheres were crosslinked with different concentrations of
      glutaraldehyde to study the effects of crosslinking extent on the growth of
      endothelial cells. The swelling ratios of the gelatin microspheres decreased from
      5.9 +/- 0.8 to 3.9 +/- 0.6 with the increase of the crosslinking extent. Basic
      fibroblast growth factors (bFGFs), which can improve endothelial cell
      proliferation as well as stimulate the formation of capillary vessels, were
      incorporated into the gelatin microspheres through ionic complexation. Sustained
      delivery of the growth factors was achieved for at least 2 weeks. The
      proliferation of the cells cultured on the bFGF-encapsulated microspheres was
      improved by about two times as compared to control and about 1.3 times as
      compared to blank microspheres, which indicated that the bioactivity of bFGF was
      well maintained, and the delivery of the growth factors directly to the cells
      significantly improved the success of this tissue engineering system.

PMID- 18636949
TI  - Self-assembling peptide amphiphile nanofibers as a scaffold for dental stem
      cells.
AB  - Dental caries remains one of the most prevalent infectious diseases in the world.
      So far, available treatment methods rely on the replacement of decayed soft and
      mineralized tissue with inert biomaterials alone. As an approach to develop novel
      regenerative strategies and engineer dental tissues, two dental stem cell lines
      were combined with peptide-amphiphile (PA) hydrogel scaffolds. PAs self-assemble
      into three-dimensional networks of nanofibers, and living cells can be
      encapsulated. Cell-matrix interactions were tailored by incorporation of the cell
      adhesion sequence RGD and an enzyme-cleavable site. SHED (stem cells from human
      exfoliated deciduous teeth) and DPSC (dental pulp stem cells) were cultured in PA
      hydrogels for 4 weeks using different osteogenic supplements. Both cell lines
      proliferate and differentiate within the hydrogels. Histologic analysis shows
      degradation of the gels and extracellular matrix production. However, distinct
      differences between the two cell lines can be observed. SHED show a spindle
      shaped morphology, high proliferation rates, and collagen production, resulting
      in soft tissue formation. In contrast, DPSC reduce proliferation, but exhibit an
      osteoblast-like phenotype, express osteoblast marker genes, and deposit mineral.
      Since the hydrogels are easy to handle and can be introduced into small defects,
      this novel system might be suitable for engineering both soft and mineralized
      matrices for dental tissue regeneration.

PMID- 18636950
TI  - Impact of hydrogen peroxide vapor room decontamination on Clostridium difficile
      environmental contamination and transmission in a healthcare setting.
AB  - OBJECTIVE: To determine whether hydrogen peroxide vapor (HPV) decontamination can
      reduce environmental contamination with and nosocomial transmission of
      Clostridium difficile. DESIGN: A prospective before-after intervention study.
      SETTING: A hospital affected by an epidemic strain of C. difficile. INTERVENTION:
      Intensive HPV decontamination of 5 high-incidence wards followed by hospital-wide
      decontamination of rooms vacated by patients with C. difficile-associated disease
      (CDAD). The preintervention period was June 2004 through March 2005, and the
      intervention period was June 2005 through March 2006. RESULTS: Eleven (25.6%) of
      43 cultures of samples collected by sponge from surfaces before HPV
      decontamination yielded C. difficile, compared with 0 of 37 cultures of samples
      obtained after HPV decontamination (P < .001). On 5 high-incidence wards, the
      incidence of nosocomial CDAD was significantly lower during the intervention
      period than during the preintervention period (1.28 vs 2.28 cases per 1,000
      patient-days; P = .047). The hospital-wide CDAD incidence was lower during the
      intervention period than during the preintervention period (0.84 vs 1.36 cases
      per 1,000 patient-days; P = .26). In an analysis limited to months in which the
      epidemic strain was present during both the preintervention and the intervention
      periods, CDAD incidence was significantly lower during the intervention period
      than during the preintervention period (0.88 vs 1.89 cases per 1,000 patient
      days; P = .047). CONCLUSIONS: HPV decontamination was efficacious in eradicating
      C. difficile from contaminated surfaces. Further studies of the impact of HPV
      decontamination on nosocomial transmission of C. difficile are warranted.

PMID- 18636953
TI  - Mucosal immunity in healthy adults after parenteral vaccination with outer
      membrane vesicles from Neisseria meningitidis serogroup B.
AB  - BACKGROUND: Nasopharyngeal carriage of meningococcus or related species leads to
      protective immunity in adolescence or early adulthood. This natural immunity is
      associated with mucosal and systemic T cell memory. Whether parenteral Neisseria
      meningitidis serogroup B (MenB) vaccination influences natural mucosal immunity
      is unknown. OBJECTIVES: To determine whether parenteral MenB vaccination affects
      mucosal immunity in young adults and whether this immunity differs from that
      induced in the blood. METHODS: Otherwise healthy volunteers were immunized with
      MenB outer membrane vesicle vaccine before and after routine tonsillectomy.
      Mucosal and systemic immunity were assessed in 9 vaccinees and 12 unvaccinated
      control subjects by measuring mononuclear cell proliferation, cytokine
      production, Th1/Th2 surface marker expression, and antibody to MenB antigens.
      RESULTS: Parenteral vaccination induced a marked increase in systemic T cell
      immunity against MenB and a Th1 bias. In contrast, although mucosal T cell
      proliferation in response to MenB neither increased nor decreased following
      vaccination, mononuclear cell interferon gamma, interleukin (IL)-5, and IL-10
      production increased, and the Th1/Th2 profile lost its Th1 bias. CONCLUSIONS:
      Parenteral MenB vaccination selectively reprograms preexisting naturally acquired
      mucosal immunity. As new-generation protein-based MenB vaccine candidates undergo
      evaluation, the impact of these vaccines on mucosal immunity in both adults and
      children will need to be addressed.

PMID- 18636955
TI  - Cost-effectiveness analysis of introduction of rapid, alternative methods to
      identify multidrug-resistant tuberculosis in middle-income countries.
AB  - BACKGROUND: Resistance to commonly used antituberculosis drugs is emerging
      worldwide. Conventional drug-susceptibility testing (DST) methods are slow and
      demanding. Alternative, rapid DST methods would permit the early detection of
      drug resistance and, in turn, arrest tuberculosis transmission. METHODS: A cost
      effectiveness analysis of 5 DST methods was performed in the context of a
      clinical trial that compared rapid with conventional DST methods. The methods
      under investigation were direct phage-replication assay (FASTPlaque-Response;
      Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO
      LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay
      (MTT; ICN Biomedicals), and direct proportion method on Lowenstein-Jensen medium.
      These were compared with the widely used indirect proportion method on Lowenstein
      Jensen medium. RESULTS: All alternative DST methods were found to be cost
      effective, compared with other health care interventions. DST methods also
      generate substantial cost savings in settings of high prevalence of multidrug
      resistant tuberculosis. Excluding the effects of transmission, the direct
      proportion method on Lowenstein-Jensen medium was the most cost-effective
      alternative DST method for patient groups with prevalences of multidrug-resistant
      tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per
      disability-adjusted life year, respectively). CONCLUSION: Alternative, rapid
      methods for DST are cost-effective and should be considered for use by national
      tuberculosis programs in middle-income countries.

PMID- 18636956
TI  - Mannose-binding lectin: ancient molecule, interesting future.

PMID- 18636957
TI  - Cauliflower mass obstructing the left main-stem bronchus.

PMID- 18636961
TI  - Let us keep the medical literature free of perjorative language and political
      bias.

PMID- 18636958
TI  - No impairment of endothelial function or insulin sensitivity with 4 weeks of the
      HIV protease inhibitors atazanavir or lopinavir-ritonavir in healthy subjects
      without HIV infection: a placebo-controlled trial.
AB  - BACKGROUND: Dyslipidemia alone does not fully explain the increase in
      cardiovascular events among patients receiving protease inhibitor (PI)-based
      treatment for human immunodeficiency virus infection. Some PIs, such as
      indinavir, directly induce endothelial dysfunction, an effect that may mediate
      that portion of the increase in cardiovascular events that is not attributable to
      dyslipidemia. METHODS: Endothelium-dependent vasodilation, insulin-mediated
      vasodilation, and whole-body and leg glucose uptake during use of a 1-h
      euglycemic hyperinsulinemic clamp (insulin infusion, 40 mU/m(2)/min) were
      measured in healthy men before and after 4 weeks of treatment with placebo (12
      men), with 400 mg atazanavir per day (9 men), or with 400 mg lopinavir and 100 mg
      ritonavir twice per day (9 men). RESULTS: Median age (36 years) and mean body
      mass index SD (23.4+/-2.6; calculated as weight in kilograms divided by the
      square of height in meters) did not differ between groups. Endothelium-dependent
      vasodilation, expressed as the percentage change in the leg blood flow response
      to intrafemoral artery infusion of 15 microg/min of the endothelium-dependent
      vasodilator methacholine, did not change after 4 weeks of treatment in any
      group:mean percentage change +/- SD, 154+/-102 from baseline and 242+/-254 at
      week 4 with atazanavir (P=.36), 76+/-62 and 86+/-79, respectively, with lopinavir
      ritonavir (P=.68), and 111+/-86 and 127+/-153, respectively,with placebo (P=.63;
      for between-group differences, P=.55). The response to the endothelium
      independent vasodilator nitroprusside was not different at week 4 for any group,
      nor was insulin-mediated vasodilation or leg or whole-body insulin-mediated
      glucose uptake (all within-group P values were 1.1). CONCLUSIONS: Unlike the
      dramatic impairment seen with indinavir, the newer PIs atazanavir and lopinavir
      ritonavir do not induce endothelial dysfunction in healthy subjects. Thus,
      endothelial dysfunction does not appear to be a PI drug class effect. The cause
      of the non-lipid-mediated increase in cardiovascular events that are reported
      with PIs remains unclear.

PMID- 18636962
TI  - Military "misadventure".

PMID- 18636963
TI  - Open-access world wide web resources on sepsis.

PMID- 18636964
TI  - Successful treatment of methicillin-resistant staphylococcus aureus meningitis
      with daptomycin.

PMID- 18636965
TI  - PKC isoenzymes differentially modulate the effect of thrombin on MAPK-dependent
      RPE proliferation.
AB  - Thrombin signalling through PAR (protease-activated receptor)-1 is involved in
      cellular processes, such as proliferation, differentiation and cell survival.
      Following traumatic injury to the eye, thrombin signalling may participate in
      disorders, such as PVR (proliferative vitreoretinopathy), a human eye disease
      characterized by the uncontrolled proliferation, transdifferentiation and
      migration of otherwise quiescent RPE (retinal pigment epithelium) cells. PARs
      activate the Ras/Raf/MEK/ERK MAPK pathway (where ERK is extracellular-signal
      regulated kinase, MAPK is mitogen-activated protein kinase and MEK is MAPK/ERK
      kinase) through the activation of G(alpha) and G(betagamma) heterotrimeric G
      proteins, and the downstream stimulation of the PLC (phospholipase C)-beta/PKC
      (protein kinase C) and PI3K (phosphoinositide 3-kinase) signalling axis. In the
      present study, we examined the molecular signalling involved in thrombin-induced
      RPE cell proliferation, using rat RPE cells in culture as a model system for PVR
      pathogenesis. Our results showed that thrombin activation of PAR-1 induces RPE
      cell proliferation through Ras-independent activation of the Raf/MEK/ERK1/2 MAPK
      signalling cascade. Pharmacological analysis revealed that the activation of
      'conventional' PKC isoforms is essential for proliferation, although thrombin
      induced phosphorylation of ERK1/2 requires the activation of atypical PKCzeta by
      PI3K. Consistently, thrombin-induced ERK1/2 activation and RPE cell proliferation
      were prevented completely by PI3K or PKCzeta inhibition. These results suggest
      that thrombin induces RPE cell proliferation by joint activation of PLC-dependent
      and atypical PKC isoforms and the Ras-independent downstream stimulation of the
      Raf/MEK/ERK1/2 MAPK cascade. The present study is the first report demonstrating
      directly thrombin-induced ERK phosphorylation in the RPE, and the involvement of
      atypical PKCzeta in this process.

PMID- 18636966
TI  - The mitochondrial pool of free amino acids reflects the composition of
      mitochondrial DNA-encoded proteins: indication of a post- translational quality
      control for protein synthesis.
AB  - Mitochondria can synthesize a limited number of proteins encoded by mtDNA
      (mitochondrial DNA) by using their own biosynthetic machinery, whereas most of
      the proteins in mitochondria are imported from the cytosol. It could be
      hypothesized that the mitochondrial pool of amino acids follows the frequency of
      amino acids in mtDNA-encoded proteins or, alternatively, that the profile is the
      result of the participation of amino acids in pathways other than protein
      synthesis (e.g. haem biosynthesis and aminotransferase reactions). These
      hypotheses were tested by evaluating the pool of free amino acids and derivatives
      in highly-coupled purified liver mitochondria obtained from rats fed on a
      nutritionally adequate diet for growth. Our results indicated that the pool
      mainly reflects the amino acid composition of mtDNA-encoded proteins, suggesting
      that there is a post-translational control of protein synthesis. This conclusion
      was supported by the following findings: (i) correlation between the
      concentration of free amino acids in the matrix and the frequency of abundance of
      amino acids in mtDNA-encoded proteins; (ii) the similar ratios of essential-to
      non-essential amino acids in mtDNA-encoded proteins and the mitochondrial pool of
      amino acids; and (iii), lack of a correlation between codon usage or tRNA levels
      and amino-acid concentrations. Quantitative information on the mammalian
      mitochondrial content of amino acids, such as that presented in the present
      study, along with functional studies, will help us to better understand the
      pathogenesis of mitochondrial diseases or the biochemical implications in
      mitochondrial metabolism.

PMID- 18636967
TI  - Tyrosine modification enhances metal-ion binding.
AB  - Tyrosine sulfation is a common modification of many proteins, and the ability to
      phosphorylate tyrosine residues is an intrinsic property of many growth-factor
      receptors. In the present study, we have utilized the peptide hormone CCK(8)
      (cholecystokinin), which occurs naturally in both sulfated and unsulfated forms,
      as a model to investigate the effect of tyrosine modification on metal-ion
      binding. The changes in absorbance and fluorescence emission on Fe(3+) binding
      indicated that tyrosine sulfation or phosphorylation increased the stoichiometry
      from 1 to 2, without greatly affecting the affinity (0.6-2.8 microM at pH 6.5).
      Measurement of Ca(2+) binding with a Ca(2+)-selective electrode revealed that
      phosphorylated CCK(8) bound two Ca(2+) ions. CCK(8) and sulfated CCK(8) each
      bound only one Ca(2+) ion with lower affinity. Binding of Ca(2+), Zn(2+) or
      Bi(3+) to phosphorylated CCK(8) did not cause any change in absorbance, but
      substantially increased the change in absorbance on subsequent addition of
      Fe(3+). The results of the present study demonstrate that tyrosine modification
      may increase the affinity of metal-ion binding to peptides, and imply that metal
      ions may directly regulate many signalling pathways.

PMID- 18636968
TI  - Dengue-4 envelope domain III fused twice within the meningococcal P64k protein
      carrier induces partial protection in mice.
AB  - A vaccine against dengue virus must be able to induce an effective and equivalent
      immune response to the four viral serotypes; however, some studies have revealed
      that DEN4 (dengue-virus serotype 4) induces a weaker immune response than the
      others in quadrivalent (tetravalent') formulations. We have previously reported
      the protective capacity, in a viral encephalitis murine model, of fusion protein
      P64k-envelope domain III of DEN1, DEN2 and DEN3. We also reported that the P64k
      protein can be used as a carrier in two different positions: the insertion
      following the first 45 amino acids and the fusion at the C-terminus. Considering
      the low immunogenicity described for DEN4, in the present study we obtained a
      novel chimaeric protein by inserting two dengue-4 envelope domains III in both
      sites of P64k (PD24), and hence increasing the presence of the virus in the final
      construct. After expression in Escherichia coli and semipurification, the protein
      exhibited a pattern of high molecular mass and was well recognized by human and
      murine polyclonal antibodies. The protein was finally evaluated in mice,
      Al(OH)(3) being employed as the adjuvant. Even though the animals exhibited low
      levels of antiviral antibodies, the recombinant protein induced significant
      protection against lethal challenge with dengue-4 virus.

PMID- 18636970
TI  - The Drosophila p21-activated kinase Mbt modulates DE-cadherin-mediated cell
      adhesion by phosphorylation of Armadillo.
AB  - Phosphorylation by tyrosine and serine/threonine kinases regulate the
      interactions between components of the cadherin-catenin cell-adhesion complex and
      thus can influence the dynamic modulation of cell adhesion under normal and
      disease conditions. Previous mutational analysis and localization experiments
      suggested an involvement of single members of the family of PAKs (p21-activated
      kinases) in the regulation of cadherin-mediated cell adhesion, but the molecular
      mechanism remained elusive. In the present study, we address this question using
      the Drosophila PAK protein Mbt, which is most similar to vertebrate PAK4.
      Previous phenotypic analysis showed that Mbt has a function to maintain adherens
      junctions during eye development and indicated a requirement of the protein in
      regulation of the actin cytoskeleton and the cadherin-catenin complex. Here we
      show that activation of Mbt leads to destabilization of the interaction of the
      Drosophila beta-catenin homologue Armadillo with DE-cadherin resulting in a
      decrease in DE-cadherin-mediated adhesion. Two conserved phosphorylation sites in
      Armadillo were identified that mediate this effect. The findings of the present
      study support the previous observation that activation of the human Mbt homologue
      PAK4 leads to anchorage-independent growth and provide a functional link between
      a PAK protein and the cadherin-catenin complex.

PMID- 18636969
TI  - C-terminal residues of mature human T-lymphotropic virus type 1 protease are
      critical for dimerization and catalytic activity.
AB  - HTLV-1 [HTLV (human T-cell lymphotrophic virus) type 1] is associated with a
      number of human diseases. HTLV-1 protease is essential for virus replication, and
      similarly to HIV-1 protease, it is a potential target for chemotherapy. The
      primary sequence of HTLV-1 protease is substantially longer compared with that of
      HIV-1 protease, and the role of the ten C-terminal residues is controversial. We
      have expressed C-terminally-truncated forms of HTLV-1 protease with and without N
      terminal His tags. Removal of five of the C-terminal residues caused a 4-40-fold
      decrease in specificity constants, whereas the removal of an additional five C
      terminal residues rendered the protease completely inactive. The addition of the
      N-terminal His tag dramatically decreased the activity of HTLV-1 protease forms.
      Pull-down experiments carried out with His-tagged forms, gel-filtration
      experiments and dimerization assays provided the first unequivocal experimental
      results for the role of the C-terminal residues in dimerization of the enzyme.
      There is a hydrophobic tunnel on the surface of HTLV-1 protease close to the C
      terminal ends that is absent in the HIV-1 protease. This hydrophobic tunnel can
      accommodate the extra C-terminal residues of HTLV-1 protease, which was predicted
      to stabilize the dimer of the full-length enzyme and provides an alternative
      target site for protease inhibition.

PMID- 18636971
TI  - Architectural factor HMGA induces promoter bending and recruits C/EBP and GATA
      during silkmoth chorion gene regulation.
AB  - A protein displaying significant similarity to mammalian HMGA (high-mobility
      group A) proteins, but also bearing unique structural features, was isolated from
      silkmoth (Bombyx mori) follicular cells. This factor, named BmHMGA, exhibits
      specific binding preference for chorion gene promoter elements and induces DNA
      bending thereon. BmHMGA deploys temporal-specific interaction with transcription
      factors BmC/EBP (C/EBP is CCAAT/enhancer-binding protein) and BmGATAbeta during
      follicle maturation. The respective protein complexes can be detected on chorion
      gene promoters in vivo, with different developmental profiles each time.
      Analogous interaction takes place on the putative promoter of the BmC/EBP gene,
      hinting towards a transcriptional circuit that is responsible for the progress of
      choriogenesis as a whole. Finally, transient suppression of BmHMGA expression led
      to down-regulation of chorion genes and the BmC/EBP gene, and revealed
      recruitment of BmC/EBP, BmGATAbeta and TFIID (transcription factor IID)/TBP (TATA
      box-binding protein) by BmHMGA. A revised model for chorion gene regulation is
      discussed in view of these findings.

PMID- 18636972
TI  - Regulation of microtubule nucleation from membranes by complexes of membrane
      bound gamma-tubulin with Fyn kinase and phosphoinositide 3-kinase.
AB  - The molecular mechanisms controlling microtubule formation in cells with non
      centrosomal microtubular arrays are not yet fully understood. The key component
      of microtubule nucleation is gamma-tubulin. Although previous results suggested
      that tyrosine kinases might serve as regulators of gamma-tubulin function, their
      exact roles remain enigmatic. In the present study, we show that a pool of gamma
      tubulin associates with detergent-resistant membranes in differentiating P19
      embryonal carcinoma cells, which exhibit elevated expression of the Src family
      kinase Fyn (protein tyrosine kinase p59(Fyn)). Microtubule-assembly assays
      demonstrated that membrane-associated gamma-tubulin complexes are capable of
      initiating the formation of microtubules. Pretreatment of the cells with Src
      family kinase inhibitors or wortmannin blocked the nucleation activity of the
      gamma-tubulin complexes. Immunoprecipitation experiments revealed that membrane
      associated gamma-tubulin forms complexes with Fyn and PI3K (phosphoinositide 3
      kinase). Furthermore, in vitro kinase assays showed that p85alpha (regulatory
      p85alpha subunit of PI3K) serves as a Fyn substrate. Direct interaction of gamma
      tubulin with the C-terminal Src homology 2 domain of p85alpha was determined by
      pull-down experiments and immunoprecipitation experiments with cells expressing
      truncated forms of p85alpha. The combined results suggest that Fyn and PI3K might
      take part in the modulation of membrane-associated gamma-tubulin activities.

PMID- 18636973
TI  - Spatial and temporal variability in VOC levels within a commercial retail
      building.
AB  - A study was performed to characterize the concentration of dozens of volatile
      organic compounds (VOCs) at 10 locations within a single large building and track
      these concentrations over a 2-year period. The study was performed at a shopping
      center (strip mall) in New Jersey. A total of 130 indoor air samples were
      collected from 10 retail stores within the shopping center and analyzed for 60
      VOCs by US EPA Method TO-15. Indoor concentrations of up to 55,100 microg/m(3)
      were measured for individual VOCs. The indoor/outdoor ratio (I/O) was as high as
      1500 for acetone and exceeded 100 at times for various compounds, indicating that
      significant indoor air sources were present. A large degree of spatial
      variability was observed between stores within the building, with concentrations
      varying by three to four orders of magnitude for some compounds. The spatial
      variability was dependent on the proximity of the sampling locations to the
      indoor sources. A large degree of temporal variability also was observed for
      compounds emitted from indoor sources, but the temporal variability generally did
      not exceed two standard deviations (sigma). For compounds not emitted from indoor
      sources at significant rates, both the spatial and temporal variability tended to
      range within an order of magnitude at each location. PRACTICAL IMPLICATIONS: Many
      cross-sectional studies have been published where the levels of volatile organic
      compounds (VOCs) were measured in indoor air at one or two locations for houses
      or offices. This study provides longitudinal data for a commercial retail
      building and also addresses spatial variability within the building. The data
      suggest that spatial and temporal variability are important considerations for
      compounds emitted from indoor sources. Elevated concentrations were found in
      retail spaces with no apparent emission sources due to their proximity to other
      retail spaces with emission sources.

PMID- 18636974
TI  - Frequency of independent origins of viviparity among caecilians (Gymnophiona):
      evidence from the first 'live-bearing' Asian amphibian.
AB  - Viviparity is reported for Gegeneophis seshachari (Gymnophiona: Caeciliidae) from
      a gravid female containing four oviductal foetuses. The oviducts are highly
      vascularized and contain patches of thickened, layered tissue similar to foetal
      gut contents. Gegeneophis seshachari probably resemble other viviparous
      caecilians in having foetuses that ingest thickened oviduct lining using
      specialized deciduous teeth. This is the first report of viviparity in Asian
      amphibians and Indo-Seychellean caeciliids. Gegeneophis is the only caecilian
      genus known to include oviparous and viviparous species, and G. seshachari is the
      smallest known viviparous caecilian. Phylogenetic analysis of mitochondrial DNA
      sequences supports assignment of G. seshachari to a monophyletic Gegeneophis.
      Character optimization indicates that viviparity has evolved independently at
      least four times within Gymnophiona--a rate of incidence relative to the number
      of extant species that is higher than for other vertebrate groups except squamate
      reptiles. Our findings strengthen the proposal that caecilian reproduction
      demands further attention.

PMID- 18636975
TI  - Low migration decreases interference competition among parasites and increases
      virulence.
AB  - Competition among different parasite genotypes within a host is predicted to
      affect virulence. The direction of this effect, however, depends critically on
      the mechanisms that parasites use to compete or to cooperate with each other. One
      mechanism that bacteria use to compete with each other is via the production of
      bacteria-killing toxins, called bacteriocins. This warfare among parasites within
      a host is predicted to reduce the rate of host exploitation, resulting in lower
      virulence. By contrast, if parasites within a host are highly related, there
      could be a reduction in within-host conflict, increasing virulence. We examined
      this idea by allowing an insect-parasitic nematode (Steinernema carpocapsae) and
      its symbiotic bacteria (Xenorhabdus nematophila) to evolve for 20 passages under
      two different migration treatments (low and high). We found that host mortality
      rates were higher in the low-migration treatment when compared with the high
      migration treatment. In addition, bacteria isolated from the same insect host
      inhibited each other's growth, but only in the high-migration treatment. These
      results show that population structure and interactions among parasites within
      hosts can be critical to understanding virulence.

PMID- 18636976
TI  - Sexual selection, sexual size dimorphism and Rensch's rule in Odonata.
AB  - Odonata (dragonflies and damselflies) exhibit a range of sexual size dimorphism
      (SSD) that includes species with male-biased (males > females) or female-biased
      SSD (males < females) and species exhibiting nonterritorial or territorial mating
      strategies. Here, we use phylogenetic comparative analyses to investigate the
      influence of sexual selection on SSD in both suborders: dragonflies (Anisoptera)
      and damselflies (Zygoptera). First, we show that damselflies have male-biased
      SSD, and exhibit an allometric relationship between body size and SSD, that is
      consistent with Rensch's rule. Second, SSD of dragonflies is not different from
      unit, and this suborder does not exhibit Rensch's rule. Third, we test the
      influence of sexual selection on SSD using proxy variables of territorial mating
      strategy and male agility. Using generalized least squares to account for
      phylogenetic relationships between species, we show that male-biased SSD
      increases with territoriality in damselflies, but not in dragonflies. Finally, we
      show that nonagile territorial odonates exhibit male-biased SSD, whereas male
      agility is not related to SSD in nonterritorial odonates. These results suggest
      that sexual selection acting on male sizes influences SSD in Odonata. Taken
      together, our results, along with avian studies (bustards and shorebirds),
      suggest that male agility influences SSD, although this influence is modulated by
      territorial mating strategy and thus the likely advantage of being large. Other
      evolutionary processes, such as fecundity selection and viability selection,
      however, need further investigation.

PMID- 18636977
TI  - Stature reconstruction using fragmentary femora in South Africans of European
      descent.
AB  - It is well documented that the intact femur has the highest correlation with
      stature and as such has been widely used in the derivation of regression
      equations for stature estimation. As intact femur is not always present for
      analyses in forensic cases, it has become necessary to derive regression
      equations for the estimation of stature from fragments of this bone. Few studies
      have presented regression equations for stature estimation from fragments of the
      femur. Because these equations are population specific, it was the aim of this
      study to derive similar equations for estimation of stature and maximum length of
      femur from measurements of the femur of South Africans of European descent. A
      sample of 50 male and 50 female complete skeletons were obtained from the Raymond
      A. Dart Collection of Human Skeletons. Total skeletal height for each of the
      skeletons was calculated using the Fully's method. Six variables were measured on
      each femur which included the vertical neck diameter, upper breadth of femur,
      epicondylar breadth, bicondylar breadth, lateral condyle length, and medial
      condyle length. Regression equations for the estimation of stature are presented.
      The range of standard error of estimate for these equations (3.71-5.31) was
      slightly higher than those obtained for intact long bones (2.13-3.79). It is
      therefore suggested that in the absence of intact femur, regression equations
      derived from the present study can provide a reliable estimate of adult stature.

PMID- 18636978
TI  - Gait analysis in forensic medicine*.
AB  - Recordings from video surveillance systems are used as evidence from crime
      scenes. It would be useful to perform comparisons between disguised perpetrators
      and suspects based on their gait. We applied functional anatomical and
      biomechanical knowledge to analyze the gait of perpetrators, as recorded on
      surveillance video. Using a structured checklist, which addresses the single body
      segments during gait, we were able to give a statement concerning the gait
      patterns. Characteristic parameters were, e.g., varus instability in the knee at
      heel strike, and larger lateral flexion of the spinal column to one side than the
      other. Based on these characteristic features, we are able to state with
      reasonable certainty whether the suspect could be the perpetrator, but it is not
      possible to identify the perpetrator positively. Nevertheless, we have been
      involved in several cases where the court has found that this type of gait
      analysis was a valuable tool.

PMID- 18636979
TI  - A D19S433 primer binding site mutation and the frequency in Japanese of the
      silent allele it causes.
AB  - Short tandem repeat studies are powerful tools for parentage analysis and for
      identification of missing persons, victims of murder, and victims of mass
      fatalities when reference samples are unavailable. The primer in the Identifiler
      kit failed to amplify an allele at the D19S433 locus, producing a silent ("null")
      allele. The causal mutation is a base change (G>A) 32 nucleotides downstream from
      the 3' end of the AAGG repeats. The silent alleles are problematical in parentage
      analysis because when transmitted, they can cause a parent-child inconsistency
      that is unrelated to Mendelian genetics. The inconsistency is sometimes termed an
      "apparent opposite homozygosity" and it produces false evidence of nonparentage.
      Alternative primers were designed to amplify the D19S433 locus alleles and they
      detect the silent allele. Frequencies of the (no longer) silent allele were
      determined to be 0.0114 in 176 people from Shizuoka (Honshu) and 0.0128 in 156
      people from Okinawa.

PMID- 18636980
TI  - A middle-aged female serial killer.
AB  - The case of a 48-year-old woman accused of killing at least 12 elderly women and
      attempting to kill another one during the last 3 years is presented. Extensive
      neuropsychological, electrophysiological, and neuropsychiatric testing showed no
      evidence of a DSM-IV-TR Axis I diagnosis, but a decrease in executive functions
      and abnormalities in the processing of affective stimuli were found. Behavioral
      and psychophysiological studies revealed dissociation between knowing how to
      behave and actually behaving in socially acceptable ways. According to the woman,
      killing was just her response to "humiliating situations." Two potentially
      significant conditions in her past history are found: (i) childhood abuse; and
      (ii) multiple head injuries. It is conjectured that the nature of her crimes,
      paranoid and personality traits, a probable frontal brain dysfunction, as well as
      a specific demographic and social context represent unusual factors accounting
      for her violent behavior.

PMID- 18636981
TI  - Palynology: its position in the field of forensic science.
AB  - Here we examine the current state of palynology in the field of forensic science.
      Forensic palynology is discussed with reference to other forensic disciplines to
      help understand what is required for its progress. Emerging developments are also
      discussed. Palynomorphs potentially deliver excellent trace evidence, fulfilling
      the requirements relating to the transfer, persistence, and detection of such
      evidence. Palynological evidence can provide very powerful investigative and
      associative evidence. Despite this, the application of palynology to forensic
      science has had mixed success. There are many anecdotal stories where pollen
      evidence has had spectacular successes. But it is extremely underutilized in most
      countries because it is labor-intensive and requires considerable expertise and
      experience, there is a lack of control over sample collection and inadequate
      resourcing and funding, and its crime-solving power is not well known. Palynology
      has been applied to forensic problems in an unstructured way, resulting in a lack
      of formalized discussion of the underlying principles. As there is renewed
      questioning of the acceptability of most evidence types in the current legal
      environment, there is a need for the establishment of palynological evidence
      through validation-type studies and experimentation, and the implementation of
      independent proficiency testing.

PMID- 18636982
TI  - JAK/STAT3 pathway is activated in spinal cord microglia after peripheral nerve
      injury and contributes to neuropathic pain development in rat.
AB  - Peripheral nerve lesion leads to the production of interleukin 6 (IL-6)-related
      neuropoietic cytokines involved in nerve protection and regeneration. This family
      of cytokines mainly signal through the signal transducer and activator of
      transcription (STAT) pathway that is locally activated in injured nerves. IL-6 is
      also involved in pain that frequently arises from peripheral nerve lesion. We
      investigated the possible activation of this major IL-6 signaling system in the
      spinal cord after peripheral nerve injury and its role in neuropathic pain.
      Ligation of L5-L6 spinal nerves (SNL) evoked an accumulation of active,
      phosphorylated form of STAT3 in microglial cells of dorsal spinal cord mostly in
      projection areas of injured nerves. SNL resulted also in a massive induction of
      IL-6 mRNA expression in dorsal root ganglia and increased concentration of IL-6
      in dorsal spinal cord. Intrathecal injection of anti-rat IL-6 antibodies
      prevented the SNL-induced accumulation of phospho-STAT3 in the spinal cord. STAT3
      pathway blockade with Janus kinase 2 inhibitor AG490 attenuated both mechanical
      allodynia and thermal hyperalgesia in SNL rats. These data show that in response
      to SNL injury Janus kinase/STAT3 system is activated mainly through IL-6
      signaling in spinal microglia and that this transduction pathway participates in
      development of pain associated with nerve alteration.

PMID- 18636983
TI  - A phase advance of the light-dark cycle stimulates production of BDNF, but not of
      other neurotrophins, in the adult rat cerebral cortex: association with the
      activation of CREB.
AB  - Circadian variation in the expression of brain-derived neurotrophic factor (BDNF)
      indicates that BDNF is involved in the regulation of diurnal rhythms in a variety
      of biological processes. However, it is still unclear which brain regions alter
      their BDNF levels in response to external light input. Therefore, in selected
      brain regions of adult male rats, we investigated diurnal variation, as well as
      the effects of a single eight-hour phase advance of the light-dark cycle, on the
      levels of BDNF and of other neurotrophins. The cerebellum, hippocampus and
      cerebral cortex containing visual cortex (VCX) showed diurnal variation in BDNF
      protein levels and the VCX also in NT-3 levels. In the VCX and the region
      containing the entorhinal cortex and amygdala (ECX), BDNF protein levels were
      increased 12 h after the phase advance, while BDNF mRNA levels were increased
      significantly in the VCX and slightly in the ECX after 4 h. After one week,
      however, BDNF protein levels were reduced in eight brain regions out of 13
      examined. BDNF levels in the ECX and VCX were significantly different between
      light rearing and dark rearing, while a hypothyroid status did not produce an
      effect. Cyclic AMP responsive element-binding protein (CREB), a transcription
      factor for BDNF, was greatly activated by the phase advance in the ECX and VCX,
      suggesting the existence of CREB-mediated pathways of BDNF synthesis that are
      responsive to external light input.

PMID- 18636984
TI  - Histone deacetylase 6 interacts with the microtubule-associated protein tau.
AB  - Histone deacetylase 6 (HDAC6), a unique cytoplasmic deacetylase, likely plays a
      role in neurodegeneration by coordinating cell responses to abnormal protein
      aggregation. Here, we provide in vitro and in vivo evidence that HDAC6 interacts
      with tau, a microtubule-associated protein that forms neurofibrillary tangles in
      Alzheimer's disease. This interaction is mediated by the microtubule-binding
      domain on tau and the Ser/Glu tetradecapeptide domain on HDAC6. Treatment with
      tubacin, a selective inhibitor of tubulin deacetylation activity of HDAC6, did
      not disrupt HDAC6-tau interaction. Nonetheless tubacin treatment attenuated site
      specific tau phosphorylation, as did shRNA-mediated knockdown of HDAC6.
      Proteasome inhibition potentiated HDAC6-tau interactions and facilitated the
      concentration and co-localization of HDAC6 and tau in a perinuclear aggresome
      like compartment, independent of HDAC6 tubulin deacetylase activity. Furthermore,
      we observed that in Alzheimer's disease brains the protein level of HDAC6 was
      significantly increased. These findings establish HDAC6 as a tau-interacting
      protein and as a potential modulator of tau phosphorylation and accumulation.

PMID- 18636985
TI  - Changes in carbohydrates, ABA and bark proteins during seasonal cold acclimation
      and deacclimation in Hydrangea species differing in cold hardiness.
AB  - Cold injury is frequently seen in the commercially important shrub Hydrangea
      macrophylla but not in Hydrangea paniculata. Cold acclimation and deacclimation
      and associated physiological adaptations were investigated from late September
      2006 to early May 2007 in stems of field-grown H. macrophylla ssp. macrophylla
      (Thunb.) Ser. cv. Blaumeise and H. paniculata Sieb. cv. Kyushu. Acclimation and
      deacclimation appeared approximately synchronized in the two species, but they
      differed significantly in levels of mid-winter cold hardiness, rates of
      acclimation and deacclimation and physiological traits conferring tolerance to
      freezing conditions. Accumulation patterns of sucrose and raffinose in stems
      paralleled fluctuations in cold hardiness in both species, but H. macrophylla
      additionally accumulated glucose and fructose during winter, indicating species
      specific differences in carbohydrate metabolism. Protein profiles differed
      between H. macrophylla and H. paniculata, but distinct seasonal patterns
      associated with winter acclimation were observed in both species. In H.
      paniculata concurrent increases in xylem sap abscisic acid (ABA) concentrations
      ([ABA](xylem)) and freezing tolerance suggests an involvement of ABA in cold
      acclimation. In contrast, ABA from the root system was seemingly not involved in
      cold acclimation in H. macrophylla, suggesting that species-specific differences
      in cold hardiness may be related to differences in [ABA](xylem). In both species
      a significant increase in stem freezing tolerance appeared long after growth
      ceased, suggesting that cold acclimation is more regulated by temperature than by
      photoperiod.

PMID- 18636986
TI  - Biomass reallocation and the mobilization of leaf resources support dune plant
      growth after sand burial.
AB  - The stimulation of dune plant growth in response to burial is a vital attribute
      allowing survival in areas of mobile sand. Numerous resource-related and
      physiological mechanisms of growth stimulation have been suggested in the past,
      but few have been tested comparatively. Manipulation experiments using Scaevola
      plumieri, an important subtropical coastal dune forming species, demonstrated
      that physiological shifts were of great importance in determining the nature of
      the stimulation response to burial. The production of stem length and replacement
      of leaf area were stimulated by burial, whereas net mass production was similar
      between buried and unburied treatments. Remobilization of buried leaf resources,
      seasonal effects, and a shift in biomass allocation to stem production played the
      greatest role in the compensatory growth response. Other factors, such as
      increased soil nutrients, changes in photosynthesis, and changes in the costs of
      producing tissue were of less importance. Thus, the stimulated growth of species
      adapted to live on mobile dunes is explained by a number of resource-related and
      physiological mechanisms acting in concert.

PMID- 18636988
TI  - The herbicide flumioxazin stimulates pathogenesis-related gene expression and
      enzyme activities in Vitis vinifera.
AB  - In this work, the capacity of the soil-applied herbicide flumioxazin (fmx) to
      trigger defence mechanisms was assessed using 6-week-old in vitro grown Vitis
      vinifera L. plantlets. Time-course studies demonstrated that the herbicide
      induced the expression of basic beta-1,3-glucanase (Vvglu), basic chitinase
      (Vvchit1b) and PR10 (VvPR10.3) genes encoding three pathogenesis-related (PR)
      proteins involved in grapevine defence against pathogens. Thus, all transcripts
      accumulated in grapevine tissues to reach maximum values after 24-72 h of
      herbicide exposure, except for VvPR10.3 gene expression, which was induced in
      roots and stems but not in leaves. Induction of PR genes was observed to a
      greater extent in roots and leaves, and its intensity diminished in the stems
      although still remained noteworthy. The activities of beta-1,3-glucanase and
      chitinase enzymes significantly increased in the whole plant after herbicide
      exposure and were still stimulated 21 days after the beginning of treatments.
      Similarly, the most remarkable effect occurred in roots. However, all enzyme
      activities tested were stimulated in the upper aerial tissues as well, indicating
      that fmx or a derived product acts systemically, likely via root uptake.

PMID- 18636987
TI  - Overexpression of the apple alcohol acyltransferase gene alters the profile of
      volatile blends in transgenic tobacco leaves.
AB  - Alcohol acyltransferases (AATs) are key enzymes in ester biosynthesis. Previous
      studies have found that AAT may be a stress-related gene. To investigate further
      the function of the apple alcohol acyltransferase gene (MdAAT2), transgenic
      tobacco plants overexpressing MdAAT2 were generated. Gas chromatography-mass
      spectroscopy analysis showed that the volatile blends were altered in these
      transgenic tobacco leaves. Although no apple-fruity volatile esters were detected
      in transgenic tobacco leaves, methyl caprylate, methyl caprate, and methyl
      dodecanoate were newly generated, and the concentrations of methyl benzoate and
      methyl tetradecanoate were significantly increased, suggesting that MdAAT2 may
      use medium-chain fatty acyl CoA and benzoyl-CoA as acyl donors together with
      methanol acceptors as substrates. Surprisingly, the concentrations of linalool
      were significantly increased in transgenic tobacco leaves, which may mediate the
      repellent effect on Myzus persicae (Sulzer) aphids. Using methyl jasmonate (MeJA)
      and wounding treatments, we found that MdAAT2 may substitute for the partial
      ability of MeJA to induce the production of linalool in transgenic plants. These
      data suggest that MdAAT2 may be involved in the response to the MeJA signal and
      may play a role in the response to biotic and abiotic stress.

PMID- 18636989
TI  - Photosynthetic activity during olive (Olea europaea) leaf development correlates
      with plastid biogenesis and Rubisco levels.
AB  - Olive leaves are known to mature slowly, reaching their maximum photosynthetic
      activity only after full leaf expansion. Poor assimilation rates, typical to
      young olive leaves, were previously associated with low stomata conductance. Yet,
      very little is known about chloroplast biogenesis throughout olive leaf
      development. Here, the photosynthetic activity and plastids development
      throughout leaf maturation is characterized by biochemical and ultrastructural
      analyses. Although demonstrated only low photosynthetic activity, the plastids
      found in young leaves accumulated both photosynthetic pigments and proteins
      required for photophosphorylation and carbon fixation. However, Rubisco (ribulose
      1,5-bisphosphate carboxylase-oxygenase), which catalyzes the first major step of
      carbon fixation and one of the most abundant proteins in plants, could not be
      detected in the young leaves and only slowly accumulated throughout development.
      In fact, Rubisco levels seemed tightly correlated with the observed
      photosynthetic activities. Unlike Rubisco, numerous proteins accumulated in the
      young olive leaves. These included the early light induced proteins, which may be
      required to reduce the risk of photodamage, because of light absorption by
      photosynthetic pigments. Also, high levels of ribosomal L11 subunit,
      transcription factor elF-5A, Histones H2B and H4 were observed in the apical
      leaves, and in particular a plastidic-like aldolase, which accounted for
      approximately 30% of the total proteins. These proteins may upregulate in their
      levels to accommodate the high demand for metabolic energy in the young
      developing plant tissue, further demonstrating the complex sink-to-source
      relationship between young and photosynthetically active mature leaves.

PMID- 18636990
TI  - Dynamics of lipid transfer by phosphatidylinositol transfer proteins in cells.
AB  - Of many lipid transfer proteins identified, all have been implicated in essential
      cellular processes, but the activity of none has been demonstrated in intact
      cells. Among these, phosphatidylinositol transfer proteins (PITP) are of
      particular interest as they can bind to and transfer phosphatidylinositol
      (PtdIns)--the precursor of important signalling molecules, phosphoinositides--and
      because they have essential functions in neuronal development (PITPalpha) and
      cytokinesis (PITPbeta). Structural analysis indicates that, in the cytosol, PITPs
      are in a 'closed' conformation completely shielding the lipid within them. But
      during lipid exchange at the membrane, they must transiently 'open'. To study
      PITP dynamics in intact cells, we chemically targeted their C95 residue that,
      although non-essential for lipid transfer, is buried within the phospholipid
      binding cavity, and so, its chemical modification prevents PtdIns binding because
      of steric hindrance. This treatment resulted in entrapment of open conformation
      PITPs at the membrane and inactivation of the cytosolic pool of PITPs within few
      minutes. PITP isoforms were differentially inactivated with the dynamics of
      PITPbeta faster than PITPalpha. We identify two tryptophan residues essential for
      membrane docking of PITPs.

PMID- 18636991
TI  - Reduced risk of cancer in schizophrenia: a role for obstetric complications?

PMID- 18636993
TI  - Alpha rhythm and hypofrontality in schizophrenia.
AB  - OBJECTIVE: To reveal the EEG correlates of resting hypofrontality in
      schizophrenia (SZ). METHOD: We analyzed the whole-head EEG topography in 14
      patients compared to 14 matched controls by applying a new parameterization of
      the multichannel EEG. We used a combination of power measures tuned for regional
      surface mapping with power measures that allow evaluation of global effects.
      RESULTS: The SZ-related EEG abnormalities include i) a global decrease in
      absolute EEG power robustly manifested in the alpha and beta frequency bands, and
      ii) a relative increase in the alpha power over the prefrontal brain regions
      against its reduction over the posterior regions. In the alpha band both effects
      are linked to the SZ symptoms measured with Positive and Negative Symptom Scales
      and to chronicity. CONCLUSION: As alpha activity is related to regional
      deactivation, our findings support the concept of hypofrontality in SZ and expose
      the alpha rhythm as a sensitive indicator of it.

PMID- 18636994
TI  - Positive and useful auditory vocal hallucinations: prevalence, characteristics,
      attributions, and implications for treatment.
AB  - OBJECTIVE: Auditory hallucinations that are viewed by patients as positive and
      useful may be barriers to treatment-seeking. The aim was to assess prevalence,
      impact, and course of, and attributions to, these voices in psychotic and non
      psychotic patients. METHOD: One hundred thirty-one patients of a Voices Clinic
      and 65 members of the Dutch Resonance Foundation were assessed with the Positive
      and Useful Voices Inquiry. Data were analyzed using Pearson's chi-square, one-way
      anova, and Crohnbach's alpha statistics. RESULTS: First voices are most often
      reported as negative. Positive voices occur more among non-psychotic subjects,
      but the specific characteristics and diagnosis are not significantly associated.
      Lifetime prevalence of positive and useful voices ranged between 40% and 60%,
      with varied prevalence rates over time. Positive voices are experienced by
      subjects as direct addresses in the third person. Perceived control of voices is
      significantly associated with the wish to preserve them. Attribution of
      protective power to positive voices has the strongest association with positive
      experience. CONCLUSION: Many patients express a desire to preserve these voices.
      Voice characteristics do not allow for validly discriminating psychotic from non
      psychotic disorders.

PMID- 18636995
TI  - Relationship between white matter volume and cognitive performance during
      adolescence: effects of age, sex and risk for drug use.
AB  - AIM: Familial drug abuse history has been shown to have an impact on cognitive
      development during adolescence. The present study examined the relationship
      between white matter volume and cognitive processing speed in adolescents with
      and without a familial substance abuse history. PARTICIPANTS: The sample
      comprised 33 female and male adolescents stratified by risk (family history
      positive, FH+) and low-risk (FH-) groups. MEASUREMENTS: Gray and white matter
      volumes were measured by segmenting magnetic resonance imaging (MRI) data. The
      neurocognitive test battery included tests that assessed processing speed, verbal
      ability and mental flexibility. FINDINGS: Age-related differences in
      neuropsychological functioning were seen but did not differ by risk group status,
      although there was some evidence for an age x gender effect. Information
      processing speed (digit symbol and Stroop word color naming) was correlated
      significantly with white matter volume; however, this pattern was observed only
      in FH- females. Cognitive performance and tissue volumes did not differ
      significantly between risk groups. CONCLUSIONS: Age-related differences in
      neuropsychological functioning were seen that might, in larger samples, prove to
      be related to risk for substance abuse in adolescents who have not yet initiated
      drug use.

PMID- 18636996
TI  - Drug withdrawal, cocaine and sedative use disorders increase the need for
      mechanical ventilation in medical patients.
AB  - AIMS: Alcohol use disorders increase the need for mechanical ventilation (MV) in
      critically ill medical, surgical and trauma patients. Studies examining other
      drug use disorders (DUD) in trauma patients have not demonstrated heightened
      rates of intensive care unit (ICU) complications. Patients with asthma and
      concurrent cocaine or heroin use disorders have an increased need for MV. The
      objective of this study is to determine if the presence of DUD and drug
      withdrawal syndromes are associated with increased need for MV in medical
      patients. DESIGN: Analysis of a national database. SETTING: The Nationwide
      Inpatient Sample, the largest all-payer in-patient database was utilized for the
      years 2002-2004. PARTICIPANTS: Adult patients with one of the six common
      diagnoses associated with medical ICU admission were included. INTERVENTION:
      None. MEASUREMENTS: Univariate analysis and multivariate logistic regression were
      performed to determine if DUD and drug withdrawal were associated independently
      with the use of MV. FINDINGS: A total 1 218 875 patients fulfilled one of the six
      diagnoses; 22 827 (1.9%) had DUD, and 102 841 (8.4%) underwent MV. Independent of
      the medical diagnosis, DUD was associated with an increased risk for requiring MV
      by univariate analysis (relative risk = 1.50, P < 0.0001). By multivariate
      analyses, sedative and cocaine use disorders remained associated with increased
      need for MV. Independent of medical diagnosis and substance, drug withdrawal was
      associated with increased odds of MV by both univariate and multivariate analysis
      (odds ratio = 2.94, P < 0.0001). CONCLUSIONS: DUD are associated with increased
      need for MV in medical patients. This study demonstrates the importance of
      screening all medical patients for DUD.

PMID- 18636997
TI  - Venlafaxine dependence in a patient with a history of alcohol and amineptine
      misuse.
AB  - BACKGROUND: Venlafaxine is an inhibitor of neuronal serotonin and noradrenaline
      re-uptake and a weak inhibitor of dopamine re-uptake. There was no indication of
      problems of abuse/dependence during the clinical trials. CASE DESCRIPTION: A 53
      year-old client with a history of alcohol and amineptine misuse and a long
      history of recurrent depression, for which he was prescribed venlafaxine tablets.
      Over time, he increased the dosage to 50 tablets daily (3750 mg). Large
      venlafaxine dosages produced amphetamine-like effects, due possibly to the
      related increase in dopamine turnover. Once hospitalized for detoxification, the
      patient had a symptomatology which was consistent with a serotonergic
      discontinuation syndrome. CONCLUSIONS: Physicians should be aware that patients
      with a history of drug and alcohol abuse might develop venlafaxine dependence.

PMID- 18636998
TI  - Mitigating risky sexual behaviors among Russian narcology hospital patients: the
      PREVENT (Partnership to Reduce the Epidemic Via Engagement in Narcology
      Treatment) randomized controlled trial.
AB  - AIM: To assess the effectiveness of a sexual risk reduction intervention in the
      Russian narcology hospital setting. DESIGN, SETTING AND PARTICIPANTS: This was a
      randomized controlled trial from October 2004 to December 2005 among patients
      with alcohol and/or heroin dependence from two narcology hospitals in St
      Petersburg, Russia. INTERVENTION: Intervention subjects received two personalized
      sexual behavior counseling sessions plus three telephone booster sessions.
      Control subjects received usual addiction treatment, which did not include sexual
      behavior counseling. All received a research assessment and condoms at baseline.
      MEASUREMENTS: Primary outcomes were percentage of safe sex episodes (number of
      times condoms were used / by number of sexual episodes) and no unprotected sex
      (100% condom use or abstinence) during the previous 3 months, assessed at 6
      months. FINDINGS: Intervention subjects reported higher median percentage of safe
      sex episodes (unadjusted median difference 12.7%; P = 0.01; adjusted median
      difference 23%, P = 0.07); a significant difference was not detected for the
      outcome no unprotected sex in the past 3 months [unadjusted odds ratio (OR) 1.6,
      95% confidence interval (CI) 0.8-3.1; adjusted OR 1.5, 95% CI 0.7-3.3].
      CONCLUSIONS: Among Russian substance-dependent individuals, sexual behavior
      counseling during addiction treatment should be considered as one potential
      component of efforts to decrease risky sexual behaviors in this HIV at-risk
      population.

PMID- 18636999
TI  - Key findings from the WHO collaborative study on substitution therapy for opioid
      dependence and HIV/AIDS.
AB  - AIMS: Opioid substitution treatment has been studied extensively in
      industrialized countries, but there are relatively few studies in
      developing/transitional countries. The aim of this study was to examine the
      effectiveness of opioid substitution treatment (OST) in less resourced countries.
      DESIGN: Longitudinal cohort study. SETTING: Purposively selected OST sites in
      Asia (China, Indonesia, Thailand), Eastern Europe (Lithuania, Poland, Ukraine),
      the Middle East (Iran) and Australia. PARTICIPANTS: Seven hundred and twenty-six
      OST entrants. MEASUREMENTS: Participants were interviewed at treatment entry, 3
      and 6 months. Standardized instruments assessed drug use, treatment history,
      physical and psychological health, quality of life, criminal involvement, blood
      borne virus (BBV) risk behaviours and prevalence of human immunodeficiency virus
      (HIV) and hepatitis C. FINDINGS: Participants were predominantly male, aged in
      their early 30s and had attained similar levels of education. Seroprevalence
      rates for HIV were highest in Thailand (52%), followed by Indonesia (28%) and
      Iran (26%), and lowest in Australia (2.6%). Treatment retention at 6 months was
      uniformly high, averaging approximately 70%. All countries demonstrated
      significant and marked reductions in reported heroin and other illicit opioid
      use; HIV (and other BBV) exposure risk behaviours associated with injection drug
      users (IDU) and criminal activity, and demonstrated substantial improvement in
      their physical and mental health and general wellbeing over the course of the
      study. CONCLUSIONS: OST can achieve similar outcomes consistently in a culturally
      diverse range of settings in low- and middle-income countries to those reported
      widely in high-income countries. It is associated with a substantial reduction in
      HIV exposure risk associated with IDU across nearly all the countries. Results
      support the expansion of opioid substitution treatment.

PMID- 18637003
TI  - Meta-analysis: narrow band imaging for lesion characterization in the colon,
      oesophagus, duodenal ampulla and lung.
AB  - BACKGROUND: Narrow band imaging is a new endoscopic technology that highlights
      mucosal surface structures and microcapillaries, which may be indicative of
      neoplastic change. AIM: To assess the diagnostic precision of narrow band imaging
      for the diagnosis of epithelial neoplasia compared to conventional histology both
      overall and in specific organs. METHODS: We performed a meta-analysis of studies
      which compared narow band imaging-based diagnosis of neoplasia with
      histopathology as the gold standard. Search terms: 'endoscopy' and 'narrow band
      imaging'. RESULTS: Five hundred and eighty-two patients and 1108 lesions in 11
      studies were included. Overall, sensitivity was 0.94 (95% confidence interval
      0.92-0.95), specificity 0.83 (0.80-0.86); weighted area under the curve was 0.96
      (standard error 0.02), diagnostic odds ratio (DOR) 72.74 (34.11-155.15). DORs
      were 66.65 (25.84-171.90), 61.19 (7.09-527.97), 69.74 (8.04-605.24) for colon,
      oesophagus and lung respectively. Studies with more than 50 patients had higher
      diagnostic precision, relative DOR 4.96 (1.28-19.27), P = 0.022. There was no
      difference in accuracy between microvessel and mucosal (pit) pattern based
      measures, relative DOR 1.29 (0.05-35.16), P = 0.87. There was significant
      heterogeneity overall between studies, Q = 31.2, P = 0.003. CONCLUSION: Narrow
      band imaging is accurate with high diagnostic precision for in vivo diagnosis of
      neoplasia across a range of organs, using simple microvessel-based measures.

PMID- 18637000
TI  - The impact of alcohol use on depressive symptoms in human immunodeficiency virus
      infected patients.
AB  - AIMS: To examine the impact of alcohol use on depressive symptoms in human
      immunodeficiency virus (HIV)-infected patients. DESIGN: Data were collected at 6
      month intervals and analyzed to evaluate the association between alcohol
      dependence and consumption on depressive symptoms using longitudinal mixed
      effects regression models controlling for specified covariates. MEASUREMENTS: The
      two independent variables were current alcohol dependence assessed using the
      Composite International Diagnostic Interview (CIDI) and past month consumption
      (heavy versus not heavy drinking) using a validated calendar-based method. The
      primary outcome was depressive symptoms as measured by the Center for
      Epidemiologic Studies Depression Scale (CES-D). PARTICIPANTS: HIV-infected adults
      with current or past alcohol problems. FINDINGS: Alcohol dependence and heavy
      alcohol use were significantly associated with higher CES-D scores in unadjusted
      models. In adjusted analyses, the association of current alcohol dependence
      persisted [mean difference in CES-D was 3.49 for dependence versus non
      dependence; 95% confidence interval (CI): 1.76-5.22]; however, the effect of
      heavy drinking was no longer statistically significant (mean difference in CES-D
      was 1.04 for heavy versus not heavy drinking; 95% CI: -0.24-2.32). CONCLUSIONS:
      Alcohol use is associated with more depressive symptoms in HIV-infected patients
      with alcohol problems. This association remains significant after adjusting for
      potential confounders only when alcohol use meets the criteria for alcohol
      dependence.

PMID- 18637004
TI  - Review article: the psychoneuroimmunology of irritable bowel syndrome--an
      exploration of interactions between psychological, neurological and immunological
      observations.
AB  - BACKGROUND: The pathogenesis of irritable bowel syndrome (IBS) is founded on
      interactive mechanisms. Disentangling these processes is a prerequisite for the
      development of effective drug therapy. AIM: To identify the interaction between
      the various factors implicated in IBS. METHODS: Articles pertaining to IBS
      pathogenesis focusing on psychoneuroimmunology were identified using following
      search terms: IBS, animal models, microbiota, probiotics, immunology, visceral
      hypersensitivity, imaging, psychology and visceral pain. RESULTS: Cerebral
      imaging using MRI and proton emission tomography scanning has revealed
      differential regional cerebral activation, whereas stimuli induced activation has
      been captured by both MRI and cortical evoked potentials. At the peripheral
      neurological level, the concept of visceral hypersensitivity has been challenged
      as perhaps representing psychological traits with symptom over-reporting or hyper
      vigilance. Gut mucosal immunology is thought to be relevant with immunological
      changes reflected as peripheral blood cytokine level changes. Molecular
      technology advances suggest a role for microbiota by activating the gut
      immunological system. These interactions have been examined in IBS animal models.
      CONCLUSIONS: Translation of animal model findings to humans is needed to link the
      various psychological, neurological and immunological changes noted in IBS. This
      analysis may identify patient sub-groups, which will ultimately be critical for
      drug testing to be focused accordingly.

PMID- 18637005
TI  - Chromosomal integration of human herpesvirus 6 DNA in anticonvulsant
      hypersensitivity syndrome: a unique opportunity for the understanding of their
      relation.

PMID- 18637006
TI  - BAFF is elevated in serum of patients with psoriasis: association with disease
      activity.

PMID- 18637007
TI  - Congenital peristernal dermal sinuses: a new entity?

PMID- 18637008
TI  - Loss-of-function polymorphisms in the filaggrin gene are associated with an
      increased susceptibility to chronic irritant contact dermatitis: a case-control
      study.
AB  - BACKGROUND: Polymorphisms in the filaggrin (FLG) gene, which result in loss of
      filaggrin production, may alter the skin barrier and are a well-known
      predisposing factor for atopic dermatitis. OBJECTIVES: As a compromised skin
      barrier and atopic dermatitis are risk factors for chronic irritant contact
      dermatitis (CICD), our objective was to determine whether polymorphisms in the
      FLG gene contribute towards susceptibility to occupational CICD. METHODS: In a
      case-control study, the FLG polymorphisms R501X and 2282del4 were determined in
      296 patients with CICD. Two hundred and seventeen apprentices in vocational
      training for high-risk occupations for CICD were chosen as controls. Data on skin
      diseases and conditions were collected by dermatologists from patients and by
      means of questionnaires from controls. RESULTS: Heterozygotes for R501X and
      2282del4, FLG null alleles, were more frequent among patients with CICD (12.5%)
      compared with controls (6.9%), resulting in an odds ratio of 1.91 (95% confidence
      interval 1.02-3.59). Among patients who were carriers of a FLG null allele, we
      found a higher lifetime prevalence of flexural eczema (62% vs. 46%; P = 0.04) and
      a higher atopy score (13 vs. 10 points; P = 0.05) compared with noncarriers. In
      the apprentice group, signs of dermatitis before the start of the vocational
      training were four times more prevalent in carriers (43%) than in noncarriers
      (10%; P < 0.001). CONCLUSIONS: Our study shows that FLG null alleles are
      associated with increased susceptibility to CICD; whether or not the FLG null
      allele is an independent risk factor needs further study.

PMID- 18637009
TI  - Termination of pregnancy by telemedicine: an ethicist's viewpoint.

PMID- 18637010
TI  - Using telemedicine for termination of pregnancy with mifepristone and misoprostol
      in settings where there is no access to safe services.
AB  - Women on Web is a service that uses telemedicine to help women access
      mifepristone and misoprostol in countries with no safe care for termination of
      pregnancy (TOP). This study reviews the telemedicine service. After an online
      consultation, women with an unwanted pregnancy of up to 9 weeks are referred to a
      doctor. If there are no contraindications, a medical TOP is conducted by mail.
      After maximising the follow up from 54.8 to 77.6%, 12.6% decided not to do the
      TOP and 6.8% of the women who did the medical TOP at home needed a vacuum
      aspiration. Telemedicine can provide an alternative to unsafe TOP. Outcomes of
      care are in the same range as TOP provided in outpatient settings.

PMID- 18637011
TI  - Spontaneous in vitro transformation of adult neural precursors into stem-like
      cancer cells.
AB  - Recent studies have found that cellular self-renewal capacity in brain cancer is
      heterogeneous, with only stem-like cells having this property. A link between
      adult stem cells and cancer stem cells remains, however, to be shown. Here, we
      describe the emergence of cancer stem-like cells from in vitro cultured brain
      stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into
      tumorigenic cell lines after expansion in vitro. These cell lines maintained
      characteristic features of stem-like cells expressing Nestin, Musashi-1 and
      CD133, but continued to proliferate upon differentiation induction. Karyotyping
      detected multiple acquired chromosomal aberrations, and syngeneic transplantation
      into the brain of adult rats resulted in malignant tumor formation. Tumors
      revealed streak necrosis and displayed a neural as well as an undifferentiated
      phenotype. Deficient downregulation of platelet-derived growth factor (PDGF)
      receptor alpha was identified as candidate mechanism for tumor cell
      proliferation, and its knockdown by siRNA resulted in a reduction of cell growth.
      Our data point to adult brain precursor cells to be transformed in malignancies.
      Furthermore, in vitro expansion of adult neural stem cells, which will be
      mandatory for therapeutic strategies in neurological disorders, also harbors the
      risk for amplifying precursor cells with acquired genetic abnormalities and
      induction of malignant tumors after transplantation.

PMID- 18637012
TI  - Monocyte chemoattractant protein-1 plays a dominant role in the chronic
      inflammation observed in Alzheimer's disease.
AB  - Chronic neuroinflammation correlates with cognitive decline and brain atrophy in
      Alzheimer's disease (AD), and cytokines and chemokines mediate the inflammatory
      response. However, quantitation of cytokines and chemokines in AD brain tissue
      has only been carried out for a small number of mediators with variable results.
      We simultaneously quantified 17 cytokines and chemokines in brain tissue extracts
      from controls (n = 10) and from patients with and without genetic forms of AD (n
      = 12). Group comparisons accounting for multiple testing revealed that monocyte
      chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8)
      were consistently upregulated in AD brain tissue. Immunohistochemistry for MCP-1,
      IL-6 and IL-8 confirmed this increase and determined localization of these
      factors in neurons (MCP-1, IL-6, IL-8), astrocytes (MCP-1, IL-6) and plaque
      pathology (MCP-1, IL-8). Logistic linear regression modeling determined that MCP
      1 was the most reliable predictor of disease. Our data support previous work on
      significant increases in IL-6 and IL-8 in AD but indicate that MCP-1 may play a
      more dominant role in chronic inflammation in AD.

PMID- 18637013
TI  - Azaspirene, a fungal product, inhibits angiogenesis by blocking Raf-1 activation.
AB  - Angiogenesis is an inevitable event in tumor progression and metastasis, and thus
      has been a compelling target for cancer therapy in recent years. Effective
      inhibition of tumor progression and metastasis could become a promising way to
      treat tumor-induced angiogenesis. We discovered that a fungus, Neosartorya sp.,
      isolated from a soil sample, produced a new angiogenesis inhibitor, which we
      designated azaspirene. Azaspirene was previously shown to inhibit human umbilical
      vein endothelial cell (HUVEC) migration induced by vascular endothelial growth
      factor (VEGF) at an effective dose, 100% of 27 micromol/L without significant
      cell toxicity. In the present study, we investigated the antiangiogenic activity
      of azaspirene in vivo. Azaspirene treatment reduced the number of tumor-induced
      blood vessels. Administration of azaspirene at 30 microg/egg resulted in
      inhibition of angiogenesis (23.6-45.3% maximum inhibition relative to the
      controls) in a chicken chorioallantoic membrane assay. Next, we elucidated the
      molecular mechanism of antiangiogenesis of azaspirene. We investigated the
      effects of azaspirene on VEGF-induced activation of the mitogen-activated protein
      kinase signaling pathway in HUVEC. In vitro experiments indicated that azaspirene
      suppressed Raf-1 activation induced by VEGF without affecting the activation of
      kinase insert domain-containing receptor/fetal liver kinase 1 (VEGF receptor 2).
      Additionally, azaspirene preferentially inhibited the growth of HUVEC but not
      that of the non-vascular endothelial cells NIH3T3, HeLa, MSS31, and MCF-7. Taken
      together, these results demonstrate that azaspirene is a novel inhibitor of
      angiogenesis and Raf-1 activation that contains a unique carbon skeleton in its
      molecular structure.

PMID- 18637014
TI  - Na+/Ca2+ exchanger inhibitor ameliorates impaired endothelium-dependent Na+
      relaxation induced by high glucose in rat aorta.
AB  - The present study was designed to investigate the effects of KB-R7943, an
      inhibitor of the Na+/Ca2+ exchanger, on impaired endothelium-dependent relaxation
      (EDR) induced by high glucose in rat isolated aorta. Both acetylcholine (ACh)
      induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent
      relaxation (EIR) were measured after aortic rings had been exposed to high
      glucose in the absence and presence of KB-R7943. Coincubation of aortic rings
      with high glucose (25 mmol/L) for 24 h resulted in a significant inhibition of
      EDR, but had no effect on EIR. After incubation of aortic rings in the presence
      of both KB-R7943 (0.1-10 micromol/L) and high glucose for 24 h, significantly
      attenuation of impaired EDR was observed. This protective effect of KB-R7943 (10
      micromol/L) was abolished by superoxide dismutase (SOD; 200 U/mL) and l-arginine
      (3 mmol/L), whereas d-arginine (3 mmol/L) had no effect. Similarly, high glucose
      decreased SOD activity and the release of nitric oxide (NO) and increased
      superoxide anion (O2(-)) production in aortic tissue. KB-R7943 significantly
      decreased O2(-) production and increased SOD activity and NO release. These
      results suggest that KB-R7943 can restore impaired EDR induced by high glucose in
      rat isolated aorta, which may be related to the scavenging of oxygen free
      radicals and enhanced NO production.

PMID- 18637015
TI  - Evidence that inhibition of spinal nitric oxide production contributes to the
      antinociceptive effects of emulsified isoflurane on formalin-induced pain in
      rats.
AB  - The aim of the present study was to investigate the contribution of spinal nitric
      oxide (NO) to the antinociceptive effects of emulsified isofluane in rats. The
      formalin test was used to assess nociceptive responses. Immunocytochemistry and
      histochemistry were performed to determine the effects of emulsified isoflurane
      on formalin-induced changes in Fos-like immunoreactive (Fos-LI)- and nicotinamide
      adenine dinucleotide phosphatediaphorase (NADPH-d)-positive neurons,
      respectively. The results showed that emulsified isofluane, administered
      intraperitoneally, significantly decreased the formalin-induced paw licking time
      and that this was attenuated by pretreatment with intrathecal injection of the NO
      precursor L-arginine. Furthermore, Fos-LI- and NADPH-d-positive neurons were
      mainly found in the ipsilateral dorsal horn after injection of formalin, some of
      which were Fos-LI/NADPH-d double-labelled neurons. Administration of emulsified
      isofluane significantly decreased Fos-LI- and NADPH-d-positive, as well as Fos
      LI/NADPH-d double-labelled, neurons. Finally, emulsified isofluane produced a
      significant reduction of NOS activity and a decrease of NO production in the
      spinal cord of formalin-treated rats. In conclusion, the results suggest that
      inhibition of spinal NO production contributes to the antinociceptive effects of
      emulsified isofluane on formalin-induced pain in rats.

PMID- 18637016
TI  - Effects of melatonin on blood pressure in stress-induced hypertension in rats.
AB  - Melatonin, acting through its receptors, is involved in numerous physiological
      processes, including blood pressure (BP) regulation. In present study, the effect
      of melatonin inhibition on stress-induced hypertension was investigated. The
      hypertensive model consisted of male Sprague-Dawley rats subjected to electrical
      foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L)
      into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive
      rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a
      competitive antagonist of melatonin MT1 and MT2 receptors, almost completely
      abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist
      4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately
      60%) the depressor effect of melatonin, whereas the MT3 receptor-selective
      antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin.
      Brain microdialysis was performed in the AHA and the rostral ventrolateral
      medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were
      detected by high-performance liquid chromatography combined with fluorescence
      detection. The results indicated that melatonin concentrations in the AHA were
      reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate
      release and increased GABA and taurine release in the RVLM, which were paralleled
      by a decrease in arterial pressure. The mRNA expression of MT2 in the AHA of SIHR
      was higher than that in normotensive control rats, whereas there was no
      significant difference in MT1 mRNA expressin between the two groups. The results
      of the present study suggest that both a decrease of melatonin and an increase in
      the MT2 receptor in the AHA are involved in the manifestation of stress-induced
      hypertension. Both MT1 and MT2 receptors participated in the antihypertensive
      effect of melatonin in the AHA. The antihypertensive effect of melatonin was
      related to the decreases in the excitatory amino acid glutamate and increases in
      the inhibitory amino acids taurine and GABA in the RVLM.

PMID- 18637017
TI  - An S296R mutation in the human androgen receptor causes activation of the
      receptor by non-androgenic steroids and stronger inhibition by the nuclear
      receptor corepressor N-coR.
AB  - Mutation of the androgen receptor (AR) is believed to contribute to androgen
      independent growth of prostate cancer. In the present study, we examined the
      functional changes associated with the novel somatic mutation S296R in the N
      terminal domain of the AR identified from one recurrent prostate cancer sample.
      The results indicate that the S296R mutation does not differ obviously from the
      wild-type AR in its ability to bind the synthetic androgen methyltrienolone, or
      in its transcriptional activity induced by dihydrotestosterone (DHT) in the
      absence or presence of the overexpression of coactivators (steroid receptor
      coactivator-1, transcription intermediary factor-2, cAMP response element-binding
      protein-binding protein and p300). However, S296R was found to differ from wild
      type AR in that its transcriptional activity could be activated by high
      concentrations (1 micromol/L) of 17beta-oestradiol and progesterone and its
      transactivity induced by DHT was more obviously inhibited by overexpression of
      the nuclear receptor corepressor N-coR in CV-1 cells. These findings indicate
      that a point mutation (S296R) in the N-terminal domain of the AR can decrease the
      ligand specificity of the AR and alter the interaction between S296R and the
      corepressor N-coR.

PMID- 18637018
TI  - Dynamic effects of respiration on aortic blood flow and its autonomic control in
      rats.
AB  - 1. Respiratory related arterial pressure variability may reflect body fluid
      status and/or cardiac sympathetic function. The underlying mechanism is not
      clear. 2. In the present study, we used an electromagnetic blood flow meter to
      measure ascending aortic blood flow, from which stroke volume was integrated, to
      study respiration-stroke volume coupling and its underlying neural regulation.
      Experiments were performed on male Sprague-Dawley rats that were anaesthetized
      with pentobarbital sodium, paralysed with pancuronium and under mechanical
      ventilation. 3. Programmed irregular ventilation evoked significant variability
      in arterial pressure, aortic flow and stroke volume signals. Good coupling was
      noted between lung volume and aortic flow, as well as between lung volume and
      stroke volume; this coupling persisted under all experimental conditions. The
      aortic flow power and stroke volume variability and the transfer magnitude of the
      lung volume-aortic flow and lung volume-stroke volume couplings were suppressed
      by 1 mg/kg propranolol, but not by 0.3 mg/kg atropine or a combination of 0.3
      mg/kg atropine and 2.5 mg/kg phentolamine. 4. These results suggest that
      respiratory related variability in aortic flow and stroke volume, which
      ultimately contributes to arterial pressure variability, is primarily under
      cardiac sympathetic control via beta-adrenoceptors in anaesthetized and
      mechanically ventilated rats.

PMID- 18637019
TI  - Panax notoginseng saponins attenuate atherosclerosis in rats by regulating the
      blood lipid profile and an anti-inflammatory action.
AB  - Previous studies have reported on the anti-atherosclerotic effects of Panax
      notoginseng saponins (PNS). The aim of the present study was to explore the
      molecular mechanisms responsible for the anti-atherosclerotic effects of PNS and
      the inflammatory response. Thirty rats were randomly divided into three groups,
      namely a control group, a group, in which zymosan A was used to induce
      inflammation (Zym group) and a PNS-treated group. Rats in the three groups were
      administered liquid paraffin (i.p.), zymosan A (20 mg/kg, i.p., once every 3
      days) or zymosan A and PNS (100 mg/kg, i.p., once daily), respectively. All
      animals were fed a high-fat diet for 9 weeks. At scheduled times, rats were
      killed, blood was collected and the aorta was removed. Pathological changes in
      aortas were observed using Sudan IV staining and transmission electron
      microscopy. Serum lipids were measured enzymatically. Whole-blood viscosity was
      observed at different shear rates. The expression of cardiovascular disease
      specific genes was determined using GEArray (SuperArray, Frederick, MA, USA).
      Western blotting was used to evaluate the expression levels of nuclear factor
      (NF)-kappaB/p65 and its inhibitor IkappaBalpha in the aortic wall. In the present
      study, typical pathological changes associated with atherosclerosis in rats
      following induction by zymosan A were alleviated by PNS treatment. In the PNS
      treated group, there was a marked reduction in total serum cholesterol,
      triglycerides and blood viscosity. In addition, PNS treatment significantly
      decreased the gene expression of some inflammatory factors, such as integrins,
      interleukin (IL)-18, IL-1beta and matrix metalloproteinases 2 and 9. The
      expression of NF-kappaB/p65 was attenuated, whereas the expression of
      IkappaBalpha was significantly increased, after treatment with PNS. In
      conclusion, it appears that PNS exerts its therapeutic effects on atherosclerosis
      through an anti-inflammatory action and regulation of the blood lipid profile and
      that an NF-kappaB signalling pathway is involved.

PMID- 18637020
TI  - cAMP produced by pituitary adenylate cyclase-activating polypeptide 27 inhibits
      atrial natriuretic peptide secretion in rabbit beating atria.
AB  - The aim of the present study was to determine the effects of increased cAMP
      levels in response to pituitary adenylate cyclase-activating polypeptide 27
      (PACAP27) on atrial atrial natriuretic peptide (ANP) secretion in rabbit atria. A
      perfused beating atrial model was used in the present study and cAMP efflux and
      ANP levels in atrial perfusates were measured by radioimmnoassay. At 100 nmol/L,
      PACAP27 increased cAMP production, which resulted in subsequent inhibition of ANP
      secretion. Nicardipine (1.0 micromol/L), an L-type Ca2+ channel blocker,
      attenuated inhibition of ANP secretion by PACAP27. Staurosporine (1.0
      micromol/L), a non-specific protein kinase inhibitor, and H-89 (1.0 micromol/L),
      a cAMP-dependent protein kinase A (PKA) inhibitor, completely blocked the
      inhibition of ANP secretion in response to PACAP27 but had no effect on PACAP27
      induced increases in cAMP. In conclusion, the results suggest that increased cAMP
      levels in response to PACAP27 negatively regulate ANP secretion via the adenylate
      cyclase-cAMP-PKA signalling pathway in rabbit atria and that L-type Ca2+ channels
      may be involved, in part, in the regulation of ANP secretion by cAMP.

PMID- 18637021
TI  - Galectin-1 on cervical epithelial cells is a receptor for the sexually
      transmitted human parasite Trichomonas vaginalis.
AB  - The extracellular protozoan parasite Trichomonas vaginalis causes the most
      prevalent non-viral sexually transmitted human infection, yet the pathogenesis of
      infection is poorly understood, and host cell receptors have not been described.
      The surface of T. vaginalis is covered with a glycoconjugate called
      lipophosphoglycan (LPG), which plays a role in the adherence and cytotoxicity of
      parasites to human cells. T. vaginalis LPG contains high amounts of galactose,
      making this polysaccharide a candidate for recognition by the galactose-binding
      galectin family of lectins. Here we show that galectin-1 (gal-1) is expressed by
      human cervical epithelial cells and binds T. vaginalis LPG. Gal-1 binds to
      parasites in a carbohydrate-dependent manner that is inhibited in the presence of
      T. vaginalis LPG. Addition of purified gal-1 to cervical epithelial cells also
      enhances parasite binding, while a decrease in gal-1 expression by small
      interfering RNA (siRNA) transfection decreases parasite binding. In contrast, the
      related galectin-7 (gal-7) does not bind T. vaginalis in a carbohydrate-dependent
      manner, and is unable to mediate attachment of parasites to host cells. Our data
      are consistent with the presence of multiple host cell receptors for T. vaginalis
      of which gal-1 is the first to be identified and highlight the importance of
      glycoconjugates in host-pathogen interactions.

PMID- 18637022
TI  - Transcriptional control and gene silencing in Plasmodium falciparum.
AB  - Infection with the apicomplexan parasite Plasmodium falciparum is associated with
      a high burden of morbidity and mortality across the developing world, yet the
      mechanisms of transcriptional control in this organism are poorly understood.
      While P. falciparum possesses many of the characteristics common to eukaryotic
      transcription, including much of the canonical machinery, it also demonstrates
      unique patterns of gene expression and possesses unusually AT-rich intergenic
      sequences. Importantly, several biological processes that are critical to
      parasite virulence involve highly regulated patterns of gene expression and
      silencing. The relative scarcity of transcription-associated proteins and
      specific cis-regulatory motifs recognized in the P. falciparum genome have been
      thought to reflect a reduced role for transcription factors in transcriptional
      control in these parasites. New approaches and technologies, however, have led to
      the discovery of many more of these elements, including an expanded family of DNA
      binding proteins, and a re-assessment of this hypothesis is required. We review
      the current understanding of transcriptional control in P. falciparum,
      specifically highlighting promoter-driven and epigenetic mechanisms involved in
      the control of transcription initiation.

PMID- 18637023
TI  - Detection and identification of bacteria intimately associated with fungi of the
      order Sebacinales.
AB  - Because of their beneficial impact on plants, the highly diverse mycorrhizal
      fungi grouped in the order Sebacinales lay claim to high ecological and
      agricultural significance. Here, we describe for the first time associations of
      Sebacinoid members with bacteria. Using quantitative PCR, denaturating gradient
      gel electrophoresis and fluorescence in situ hybridization, we detected an
      intimate association between Piriformospora indica and Rhizobium radiobacter, an
      alpha-Proteobacterium. The stability of the association, vertical transmission of
      the bacteria during asexual fungal reproduction and fungal plant colonization was
      monitored using R. radiobacter-specific primers. Treatment of mycelium or fungal
      protoplasts with antibiotics highly efficient against the free bacteria failed to
      cure the fungus. Barley seedlings dip-inoculated with R. radiobacter showed
      growth promotion and systemic resistance to the powdery mildew fungus Blumeria
      graminis comparable to P. indica inoculation. By screening additional isolates of
      the Sebacina vermifera complex, three species-specific associations with bacteria
      from the genera Paenibacillus, Acinetobacter and Rhodococcus were found. These
      findings suggest that Sebacinales species regularly undergo complex interactions
      involving host plants and bacteria reminiscent of other ectomycorrhizal and
      endomycorrhizal associations.

PMID- 18637024
TI  - Synovium-derived stem cell-based chondrogenesis.
AB  - Synovium is considered a candidate source of cells for cartilage tissue
      engineering. Compared with mesenchymal stem cells (MSCs) from other sources,
      synovium-derived stem cells (SDSCs) have a higher capacity for chondrogenic
      differentiation. Our objective was to define cocktails of growth factors that
      support the growth and chondrogenic differentiation of SDSCs in chemically
      defined medium. We established a fast and highly selective technique of negative
      isolation of SDSC populations. The individual and combined effects of three
      growth factors-transforming growth factor-beta1 (TGF-beta1), insulin-like growth
      factor I (IGF-I), and basic fibroblast growth factor (FGF-2)-were evaluated in
      serum-free pellet cultures of SDSCs for the chondrogenesis of SDSCs using
      histology, biochemical analysis, and real-time RT-PCR. In vitro studies
      identified TGF-beta1 as the key factor for both the growth and chondrogenesis of
      SDSCs. The highest rates of SDSC growth were observed with the synergistic
      interaction of all three factors. With respect to chondrogenic differentiation of
      SDSCs, the interaction of TGF-beta1 and IGF-I applied simultaneously was superior
      to the sequential application of these two factors or any other combination of
      growth factors studied. Based on these findings, we propose a two-step protocol
      for the derivation of chondrogenic SDSCs: a cocktail of TGF-beta1, IGF-I, and FGF
      2 is applied first to induce cell growth followed by a cocktail of TGF-beta1 and
      IGF-I applied to induce chondrogenesis.

PMID- 18637025
TI  - MUC16 expression during embryogenesis, in adult tissues, and ovarian cancer in
      the mouse.
AB  - Cancer antigen 125 (CA125) is an antigen that is elevated in the serum of women
      with ovarian carcinoma, but can also be detected in serum from healthy women.
      CA125 is expressed in 80% of human ovarian cancers, as well as in normal adult
      endometrium, lung, and amnion. The gene encoding human CA125 was identified as
      MUCIN16 (MUC16). A database search identified the orthologous mouse gene, Muc16.
      Reverse transcription-polymerase chain reaction and RNA in situ hybridization
      detected Muc16 transcripts in the surface epithelia of the upper respiratory
      tract, the mesothelia lining body cavities and the internal organs, as well as
      male and female reproductive organs, and the amnion. Antibodies raised against
      human MUC16 do not recognize mouse MUC16. Therefore, a rabbit anti-mouse
      polyclonal antibody against recombinant mouse MUC16 was generated.
      Immunohistochemistry using this anti-mouse MUC16 antibody revealed expression in
      the luminal epithelia of the trachea, the epithelia of the secretory glands in
      the oral cavity, the surface of the olfactory epithelia, as well as mesothelial
      cells lining body cavities (i.e., pleural, peritoneal, and pelvic cavities), and
      male and female reproductive organs. In addition, MUC16 protein was detected in
      other cell types, such as the surface epithelia of the cochlear duct and chief
      cells of the stomach, suggesting multiple roles for MUC16. In mouse serous
      epithelial ovarian cancer, MUC16 protein was detected at the apical surface of
      well-differentiated tumors, but not poorly differentiated tumors. These findings
      document the presence of MUC16 in murine ovarian cancer and in normal tissues and
      provide a foundation for future functional studies.

PMID- 18637026
TI  - Retinoic acid maintains self-renewal of murine embryonic stem cells via a
      feedback mechanism.
AB  - Embryonic stem cells (ESCs) are pluripotent cells derived from the inner cell
      mass (ICM) that are able to self-renew or undergo differentiation depending on a
      complex interplay of extracellular signals and intracellular factors. However,
      the feedback regulation of differentiation-dependent ESC self-renewal is poorly
      understood. Retinoic acid (RA), a derivative of vitamin A, plays a critical role
      in ESC differentiation and embryogenesis. In the present study, we demonstrate
      that short-term treatment of murine (m) ESCs with RA during the early
      differentiation stage prevented spontaneous differentiation of mESCs. The RA
      treated cells maintained self-renewal capacity and could differentiate into
      neuronal cells, cardiomyocytes, and visceral endoderm cells derived from three
      germ layers. The differentiation-inhibitory effect of RA was mimicked by
      conditioned medium from RA-treated ESCs and was accompanied with up-regulated
      expression of leukemia inhibitory factor (LIF), Wnt3a, Wnt5a, and Wnt6. Such RA
      induced prevention of ESC differentiation was attenuated by a neutralizing
      antibody against LIF or by a specific Wnt antagonist Fz8-Fc and was totally
      reversed in the presence of both of them. Furthermore, knock-down of beta
      catenin, a component of the Wnt signaling pathway, by small interfering RNA
      counteracted the effect of RA. In addition, RA treatment enhanced expression of
      endodermal markers GATA4 and AFP but inhibited expression of primitive ectodermal
      marker Fgf-5 and mesodermal marker Brachyury. These findings reveal a novel role
      of RA in ESC self-renewal and provide new insight into the regulatory mechanism
      of differentiation-dependent self-renewal of ESCs, in which Wnt proteins and LIF
      induced by RA have the synergistic action. The short-term treatment of ESCs with
      RA also offers a unique model system for study of the regulatory mechanism that
      controls self-renewal and specific germ-layer differentiation of ESCs.

PMID- 18637027
TI  - Structural requirements for antimicrobial versus chemoattractant activities for
      dermaseptin S9.
AB  - Dermaseptin S9 (Drs S9), GLRSKIWLWVLLMIWQESNKFKKM, isolated from frog skin, does
      not resemble any of the cationic and amphipathic antimicrobial peptides
      identified to date, having a highly hydrophobic core sequence flanked at either
      side by cationic termini. Previous studies [Lequin O, Ladram A, Chabbert A,
      Bruston F, Convert O, Vanhoye D, Chassaing G, Nicolas P & Amiche M (2006)
      Biochemistry45, 468-480] demonstrated that this peptide adopted a non-amphipathic
      alpha-helical conformation in trifluoroethanol/water mixtures, but was highly
      aggregated in aqueous solutions and in the presence of sodium dodecyl sulfate
      micelles. Circular dichroism, FTIR and attenuated total reflectance FTIR
      spectroscopies, combined with a surface plasmon resonance study, show that Drs S9
      forms stable and ordered beta-sheet aggregates in aqueous buffers or when bound
      to anionic or zwitterionic phospholipid vesicles. These structures slowly
      assembled into amyloid-like fibrils in aqueous environments via spherical
      intermediates, as revealed by electron microscopy and Congo red staining. Drs S9
      induced the directional migration of neutrophils, T lymphocytes and monocytes.
      Interestingly, the antimicrobial and chemotactic activities of Drs S9 are
      modulated by its amyloid-like properties. Whereas spherical oligomers of Drs S9
      exhibit antimicrobial activity, the soluble, weakly self-associated forms of Drs
      S9 act on human leukocytes to promote chemotaxis and/or immunological response
      activation in the same range of concentration as amyloidogenic peptides Abeta(1
      42), the most fibrillogenic isoform of amyloid beta peptides, and the prion
      peptide PrP(106-126).

PMID- 18637028
TI  - Peripheral blood smear in a case of intravascular lymphoma.

PMID- 18637029
TI  - Is International Prognostic Scoring System (IPSS) still standard in predicting
      prognosis in patients with myelodysplastic syndrome? External validation of the
      WHO Classification-Based Prognostic Scoring System (WPSS) and comparison with
      IPSS.
AB  - BACKGROUND: This study was undertaken to evaluate the prognostic value of the WHO
      Classification-Based Prognostic Scoring System (WPSS) and to compare it with that
      of the International Prognostic Scoring System (IPSS). PATIENTS AND METHODS: 149
      patients de novo diagnosed as having myelodysplastic syndrome between December
      1994 and February 2007, were evaluated retrospectively. RESULTS: WPSS presented
      an excellent method for risk-stratifying patients into five subgroups, with
      different risks of death and leukaemic evolution. On univariate analysis, three
      components of WPSS - cytogenetic risk, WHO category and transfusion dependency -
      had good correlations with overall survival (OS) and time to leukaemic evolution
      (TTL). However, one component of IPSS - number of peripheral cytopenias - did not
      correlate with OS or TTL. WPSS could distinguish the truly low-risk patients
      (very low) who had an excellent long-term survival with rare leukaemic evolution,
      while IPSS could not. These patients should be managed with clinical observation
      and delayed treatment strategies. Furthermore, on multivariate analysis for OS,
      WPSS was found to be an independent prognostic factor for survival along with age
      [P = 0.04; hazard ratio (HR) = 1.71; 95% confidence interval (CI) 1.02-2.85] and
      lactate dehydrogenase (LDH) (P = 0.002; HR = 2.47; 95% CI 1.41-4.31). On the
      other hand, the prognostic significance of IPSS was not confirmed. CONCLUSION:
      These results suggest that the WPSS might be a more powerful predictor of
      prognosis than IPSS and that independent validation of several other, larger data
      sets should be necessary.

PMID- 18637030
TI  - Incidence of bacterial and fungal infections in newly diagnosed acute myeloid
      leukaemia patients younger than 65 yr treated with induction regimens including
      fludarabine: retrospective analysis of 224 cases.
AB  - OBJECTIVES: Infections are the major cause of morbidity and mortality in patients
      with acute myeloid leukaemia (AML). They primarily occur during the first course
      of induction chemotherapy and may increase the risk of leukaemia relapse, due to
      a significant delay in consolidation therapy. The intensification of induction
      chemotherapy and the use of non-conventional drugs such as fludarabine are
      considered responsible for the increased risk of infections. METHODS: In this
      study, we retrospectively analysed the infections occurred in 224 newly diagnosed
      AML patients </=65 yr, consecutively treated between 1997 and 2002 with an
      induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with
      or without etoposide (FLAI/FLAIE), in the context of three multicentric
      prospective trials (AML97, AML99, AML02). RESULTS: During the induction phase,
      146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and
      47 (21%) patients had Gram-negative and positive bacteremias, respectively, and
      10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The
      fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven
      IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had
      FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias,
      respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality
      rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was
      14%, 5% and 80% respectively. Interestingly, the overall incidence of
      microbiologically documented infections during induction was 38% and the
      incidence of probable/proven IFIs during the induction/consolidation programme
      was 7%. No infections caused by viruses or opportunistic pathogens were observed
      neither during induction, nor during consolidation. CONCLUSIONS: These data,
      although retrospectively collected, suggest that fludarabine-based chemotherapy
      is not associated with an increased incidence of infections, in particular IFIs,
      compared to conventional regimens commonly used for AML induction.

PMID- 18637031
TI  - A systematic review of phase II trials of thalidomide/dexamethasone combination
      therapy in patients with relapsed or refractory multiple myeloma.
AB  - Thalidomide monotherapy in relapsed/refractory multiple myeloma (MM) has a
      response rate of 30%. The combination of thalidomide with dexamethasone
      (Thal/Dex) is expected to improve responses, but it is unknown if the combination
      increases the rate of adverse events. Here, we conducted a systematic review of
      studies evaluating Thal/Dex in relapsed/refractory MM. Twelve studies were
      included, comprising 451 patients. The response rate (CR and PR) was 46% (95% CI
      42-51%). Therapy-related toxicity was comparable to thalidomide monotherapy and
      included somnolence (26%, 95% CI 22-31%), constipation (37%, 95% CI 32-42%) and
      peripheral neuropathy (27%, 95% CI 23-32%). Only venous thromboembolism appeared
      to occur more often with Thal/Dex (5%, 95% CI 3-8%). Thus, using Thal/Dex results
      in an improved response rate in relapsed/refractory MM, with a toxicity rate
      comparable to thalidomide monotherapy.

PMID- 18637032
TI  - Significant cytotoxic activity in vitro of the EGFR tyrosine kinase inhibitor
      gefitinib in acute myeloblastic leukaemia.
AB  - OBJECTIVES: Gefitinib inhibits epidermal growth factor receptor (EGFR)
      signalling, but may also act by non-EGFR dependent mechanisms. We have
      investigated the activity of gefitinib in haematological tumour cells, in
      particular acute myeloblastic leukaemia (AML). METHODS: Cytotoxic activity of
      gefitinib, alone or in combination with standard anti-leukaemic drugs, was
      assessed by the short-term fluorometric microculture cytotoxicity assay in tumour
      cells from 117 patients representing five haematological and five non
      haematological malignancies. In AML, the EGFR status was analysed by
      immunochemistry. Gefitinib-induced apoptosis was investigated in a subset of AML
      samples, as well as in the leukaemia cell line MV-4-11, using a multiparametric
      high content screening assay. To confirm activation of caspase-3 in cells treated
      with gefitinib, a blocking test was carried out in which MV4-11 cells were
      pretreated with the specific caspase inhibitor DEVD-FMK. RESULTS: Gefitinib
      showed highest cytotoxic activity in AML (n = 19) with many samples being
      sensitive at concentrations achievable in clinical practice (<10 microM), and no
      difference between previously untreated and relapsed patients. No correlation
      between the activity of gefitinib and standard antileukaemic drugs (cytarabine,
      doxorubicin, etoposide) was observed. Combining gefitinib with these drugs
      resulted in mainly additive or synergistic (etoposide) effects, with no evidence
      of sequence dependency. The AML cells did not express the EGFR. Gefitinib induced
      apoptosis, which was at least partly mediated by activation of the caspase-3
      pathway. CONCLUSION: In vitro, gefitinib has significant cytotoxic activity in
      AML by inducing apoptosis through non-EGFR dependent pathways.

PMID- 18637033
TI  - Case-control study of patients with essential tremor in Latvia.
AB  - BACKGROUND: Essential tremor (ET) is the most prevalent inherited movement
      disorder. ET has been mapped on chromosomes 2 and 3, but causative genes are not
      known. METHODS: We genotyped 16 microsatellite markers in a case-control cohort
      consisting of 104 patients and 116 controls. RESULTS: No significant difference
      between allele frequencies was found. The highest difference of frequencies was
      found in allele 171 of the marker D2S220 (OR 0.13, 95% CI 0.02-1.03, P = 0.05).
      In addition, we investigated the distribution of suspected disease gene DRD3
      Ser9Gly polymorphism in the same patients and controls. CONCLUSION: There was not
      a significant difference in genotypic distribution between disease group and
      control subjects (chi2 =2.8, P = 0.25).

PMID- 18637034
TI  - Proxy ratings from multiple sources: disagreement on the impact of multiple
      sclerosis on daily life.
AB  - BACKGROUND AND PURPOSE: The use of self-report measurements may be problematic in
      patients with limitations that interfere with reliable self-assessment like
      cognitive impairment, as may be the case in multiple sclerosis (MS). In these
      situations proxy respondents, such as close relatives or healthcare providers,
      may provide valuable information. To examine the accuracy and value of healthcare
      providers and close relatives to assess disease impact of MS. METHODS: MS
      patients, close relatives and healthcare providers completed the Multiple
      Sclerosis Impact Scale (MSIS-29) before and after a rehabilitation program.
      Agreement between outcomes was assessed by calculating mean absolute and
      directional differences and intraclass correlation coefficients. RESULTS:
      Comparison of ratings between patients and proxy respondents revealed low levels
      of agreement. Close relatives appeared to significantly overestimate the disease
      impact of MS whereas healthcare providers tended to underestimate the disease
      impact of MS. CONCLUSION: Caution is advised when incorporating close relatives
      and healthcare providers as proxy respondents in a rehabilitation setting.
      However, when close relatives are consulted, one should expect a certain level of
      overestimation of disease impact. When consulting healthcare providers, one
      should expect a certain level of underestimation of disease impact.

PMID- 18637035
TI  - No evidence of association between frontotemporal dementia and major European
      mtDNA haplogroups.
AB  - BACKGROUND AND PURPOSE: Mitochondrial DNA (mtDNA) inherited variability
      (haplogroup/sub-haplogroup) is currently emerging as not being neutral with
      respect to several complex traits like neurodegenerative diseases. Here we
      investigated the association of European mtDNA haplogroups/sub-haplogroups with
      frontotemporal dementia (FTD). METHOD AND RESULTS: A case-control study was
      carried out on 114 patients with FTD (68 sporadic and 46 familial) and 180
      controls, matched for age, gender and ethnicity. No association was found.
      CONCLUSIONS: European mtDNA haplogroups/sub-haplogroups are unlikely to play a
      major role in the risk of developing the disease.

PMID- 18637036
TI  - GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and
      persistence.
AB  - BACKGROUND AND PURPOSE: Persistent intrathecal production of IgG autoantibodies
      against glutamic acid decarboxylase 65 (GAD65 IgG) and oligoclonal IgG of
      undetermined specificity has been reported in stiff person syndrome (SPS).
      METHODS: To chart the avidity and clonal patterns of GAD65 IgG, we performed
      scatchard plot of binding characteristics and isoelectric focusing-immunoblot of
      cerebrospinal fluid (CSF) and serum from five SPS patients. RESULTS: Oligoclonal
      GAD65 IgG bands, predominantly restricted to the IgG1 subclass, were detected in
      CSF and serum in all patients. The distribution of GAD65-specific IgG bands in
      serum and CSF revealed intrathecal synthesis of oligoclonal GAD65 IgG in all five
      patients, whilst radioimmunoassay demonstrated intrathecal synthesis of GAD65 IgG
      in four. The binding avidity of GAD65 IgG from CSF was more than 10 times higher
      than in serum in two of the patients but did not differ substantially in the
      remaining three. These differences were not related to symptom severity. The
      pattern of oligoclonal GAD65 IgG bands in CSF and serum in three patients
      examined remained unchanged for up to 7 years after symptom debut. CONCLUSION:
      This study confirms the persistent systemic and intrathecal production of GAD65
      specific IgG in SPS, and further shows that this immune response is oligoclonal
      and mediated by a stable population of affinity maturated B cell clones.

PMID- 18637037
TI  - Consistency of the Babinski reflex and its variants.
AB  - BACKGROUND AND PURPOSE: The Babinski Reflex, first described in 1896, is still an
      integral part of the neurological examination. Many have studied the consistency
      of this reflex, but none have compared the inter- and intra-observer consistency
      of the Babinski reflex and its variants. METHODS: Thirty-four subjects were
      examined by six neurologists. The Babinski, Gordon, Chaddock, and Oppenheim
      reflexes were tested, and each neurologist concluded if the plantar response was
      flexor or extensor. Six subjects were re-tested 1 week later to determine intra
      observer consistency. RESULTS: The Babinski reflex had the highest interobserver
      consistency with a kappa value of 0.5491. The Chaddock, Oppenheim, and Gordon
      reflexes had kappa values of 0.4065, 0.3739, and 0.3515, respectively. For intra
      observer consistency, Gordon was the most consistent with a kappa value of
      0.6731. When reflexes were combined in pairs, the Babinski and Chaddock reflexes
      together were the most reliable. CONCLUSIONS: The Babinski reflex was shown to be
      the most consistent between examiners. The Gordon reflex had the highest intra
      observer consistency; however, the small sample size should limit conclusions
      drawn from this calculation. Clinicians often utilize more than one reflex to
      examine the plantar response; the combination of the Babinski and Chaddock
      reflexes was the most reliable.

PMID- 18637038
TI  - Efficacy and safety of felbamate in children under 4 years of age: a
      retrospective chart review.
AB  - BACKGROUND AND PURPOSE: To review our experience of the efficacy and tolerability
      of felbamate in children younger than 4 years. METHODS: We used a retrospective
      chart review to identify 53 children with seizures who were younger than 4 years.
      Efficacy was evaluated based on the occurrence of responsiveness, defined as
      seizure frequency reduction of more than 50% for a minimum period of 4 months.
      Tolerability was based on parent-reported side effects. RESULTS: Twenty-two (41%)
      patients resulted to be responders and 31 (59%) did not. By univariate analysis,
      those achieving seizure remission were probably much older, to have a shorter
      history of epilepsy and a lower frequency of seizures before felbamate therapy.
      The number of antiepileptic drugs (AEDs) used before felbamate therapy was the
      only significant predictor of the duration of response to felbamate, with a
      longer responsiveness to the drug seen in those who were placed under fewer than
      three AEDs before felbamate compared with those who had taken more than three
      (median, 16 months vs. 7 months; P < 0.0084). Side effects occurred in 30% of the
      subjects, but these did not require discontinuation of the drug. DISCUSSION:
      Felbamate is an effective medication for a wide range of epilepsy syndromes in
      children younger than 4 years. Although caution is necessary when the drug is
      used in children, felbamate might represent a possible option for the treatment
      of epilepsy in this age group.

PMID- 18637039
TI  - Effects of extracellular calcium on the growth-differentiation switch in
      immortalized keratinocyte HaCaT cells compared with normal human keratinocytes.
AB  - The keratinocyte growth and differentiation switch, tightly regulated by several
      mechanisms, is generally associated with decreased proliferation, cell cycle
      arrest in G0/G1 phase and expression of epidermal differentiation markers, such
      as keratin 1 (K1), keratin 10 (K10) and involucrin. In vitro, the spontaneously
      immortalized human keratinocyte cell line HaCaT is often used as a model to study
      keratinocyte functions. Comparative differentiation studies between HaCaT cells
      and normal human keratinocytes (NHK) over an extended time-period have rarely
      been reported. Therefore, we studied their switch from a proliferating to a
      differentiated state over 13 days. As culture conditions involved changes in
      cellular responses, cells were cultured in a specific medium for keratinocyte
      growth and differentiation was induced by increasing extracellular calcium
      concentration from 0.09 to 1.2 mm. In NHK, addition of calcium-induced
      morphological changes and concomitant decreased proliferation. For HaCaT cells,
      calcium addition resulted in morphological changes, but in an unexpected manner,
      cells were more proliferative than when cultured at low calcium levels. HaCaT
      cell hyperproliferation correlated with cell cycle analysis, showing an
      accumulation in S/G2-M phases. Furthermore, RT-PCR and western blot analysis
      revealed a delay in the expression of the differentiation markers K1, K10 and
      involucrin in HaCaT cells compared with NHK. In conclusion, even though calcium
      induced differentiation was not associated with a decreased cell proliferation,
      HaCaT cells conserved properties characteristic of differentiation.

PMID- 18637040
TI  - Molecular characterization of bacterial communities mineralizing benzene under
      sulfate-reducing conditions.
AB  - The microbial communities of in situ reactor columns degrading benzene with
      sulfate as an electron acceptor were analyzed based on clone libraries and
      terminal restriction fragment length polymorphism fingerprinting of PCR-amplified
      16S rRNA genes. The columns were filled with either lava granules or sand
      particles and percolated with groundwater from a benzene-contaminated aquifer.
      The predominant organisms colonizing the lava granules were related to
      Magnetobacterium sp., followed by a phylotype affiliated to the genera
      Cryptanaerobacter/Pelotomaculum and several Deltaproteobacteria. From the sand
      filled columns, a stable benzene-degrading consortium was established in sand
      filled laboratory microcosms under sulfate-reducing conditions. It was composed
      of Delta- and Epsilonproteobacteria, Clostridia, Chloroflexi, Actinobacteria and
      Bacteroidetes. The most prominent phylotype of the consortium was related to the
      genus Sulfurovum, followed by Desulfovibrio sp. and the
      Cryptanaerobacter/Pelotomaculum phylotype. The proportion of the latter was
      similar in both communities and significantly increased after repeated benzene
      spiking. During cultivation on aromatic substrates other than benzene, the
      Cryptanaerobacter/Pelotomaculum phylotype was outcompeted by other community
      members. Hence, this organism appears to be specific for benzene as a growth
      substrate and might play a key role in benzene degradation in both communities.
      Based on the possible functions of the community members and thermodynamic
      calculations, a functional model for syntrophic benzene degradation under sulfate
      reducing conditions is proposed.

PMID- 18637041
TI  - Reporter genes for real-time in vive monitoring of Ochrobactrum anthropi
      infection.
AB  - Despite the increasing interest in Ochrobactrum anthropi as an emerging
      nosocomial pathogen resistant to most commonly used antimicrobials, relatively
      little is known about the pathogenesis and factors contributing to its virulence.
      Also, many aspects of interaction between Ochrobactrum spp. and their hosts
      remain unclear. The ability to monitor O. anthropi infection in the host will
      facilitate our understanding of the pathogenic mechanisms and will lead to better
      choices of antimicrobial or additional therapeutic strategies. We have
      demonstrated the ability to stably express three reporter genes (green
      fluorescence protein GFP, red fluorescence protein RFP and luciferase Lux) and
      track the infection in a J774A.1 murine macrophage cell line as well as in the
      BALB/c mouse. Our results suggest that these reporter genes should improve
      genetic studies in O. anthropi, particularly those aimed at understanding
      pathogenesis, virulence factors and host interaction.

PMID- 18637042
TI  - Lipid biomarkers, pigments and cyanobacterial diversity of microbial mats across
      intertidal flats of the arid coast of the Arabian Gulf (Abu Dhabi, UAE).
AB  - Variations in morphology, fatty acids, pigments and cyanobacterial community
      composition were studied in microbial mats across intertidal flats of the arid
      Arabian Gulf coast. These mats experience combined extreme conditions of
      salinity, temperature, UV radiation and desiccation depending on their tidal
      position. Different mat forms were observed depending on the topology of the
      coast and location. The mats contained 63 fatty acids in different proportions.
      The increased amounts of unsaturated fatty acids (12-39%) and the trans/cis ratio
      (0.6-1.6%) of the cyanobacterial fatty acid n-18:1omega9 in the higher tidal mats
      suggested an adaptation of the mat microorganisms to environmental stress.
      Chlorophyll a concentrations suggested lower cyanobacterial abundance in the
      higher than in the lower intertidal mats. Scytonemin concentrations were
      dependent on the increase in solar irradiation, salinity and desiccation. The
      mats showed richness in cyanobacterial species, with Microcoleus chthonoplastes
      and Lyngbya aestuarii morphotypes as the dominant cyanobacteria. Denaturing
      gradient gel electrophoresis patterns suggested shifts in the cyanobacterial
      community dependent on drainage efficiency and salinity from lower to higher
      tidal zones. We conclude that the topology of the coast and the variable extreme
      environmental conditions across the tidal flat determine the distribution of
      microbial mats as well as the presence or absence of different microorganisms.

PMID- 18637043
TI  - The effect of sugar concentration and temperature on growth and volatile phenol
      production by Dekkera bruxellensis in wine.
AB  - The wine spoilage yeast Dekkera bruxellensis was evaluated for the production of
      4-ethylphenol under low concentrations (0.02-20 g L(-1)) of glucose and fructose
      in synthetic media. Measurable amounts of 4-ethylphenol were produced over 0.2 g
      L(-1) of each sugar. The yeast growth rate and amount of biomass formed increased
      from 0.2 to 20 g L(-1) of glucose or fructose, being accompanied by increasing
      production of 4-ethylphenol. In red wines, the production of 4-ethylphenol was
      only observed in the presence of growing populations of indigenous or inoculated
      strains of D. bruxellensis. The production rate of 4-ethylphenol varied between
      22 and 93 mug day(-1) either with inoculated strains or wild populations in
      bottled wines. The production rate of 4-ethylphenol as a function of the increase
      in the number of cells varied from 349 to 1882 mug L(-1) per one log CFU mL(-1).
      The effect of temperature on cellular viability and 4-ethylphenol production was
      tested in red wines with indigenous or inoculated strains of D. bruxellensis.
      Incubation temperatures of 15, 20 and 25 degrees C allowed cellular growth and
      volatile phenol production. Increasing incubation temperatures to 36 degrees C
      induced full viability loss of 10 strains of D. bruxellensis within <12 h.

PMID- 18637044
TI  - Intraoral condition in children with juvenile idiopathic arthritis compared to
      controls.
AB  - AIMS: The aims of this study were to compare the periodontal conditions in
      children and adolescents with juvenile idiopathic arthritis (JIA) in comparison
      to age-matched healthy individuals, and to describe intraoral health in relation
      to medical assessments. DESIGN: Forty-one JIA patients, 10-19 years old, were
      compared to 41 controls. Plaque, calculus, probing depth, bleeding on probing,
      clinical attachment loss, as well as mucosal lesions were registered. Marginal
      bone level was recorded on radiographs. A questionnaire was included. Data were
      analysed with chi-squared test, Fisher's exact test, and Mann-Whitney U-test (P <
      0.05). RESULTS: The JIA patients reported pain from jaws (P = 0.001), hands (P =
      0.001), and oral ulcers (P = 0.015) more often than controls. They avoided
      certain types of food because of oral ulcers (P = 0.037). The frequencies of
      sites with plaque (32% vs. 19%, P = 0.013), calculus (11% vs. 5%, 5 = 0.034),
      bleeding on probing (26% vs. 14%, P < 0.01), and probing depth 2 mm (32% vs. 2%,
      P < 0.001) were higher among JIA patients. No sites with attachment loss or
      reduced marginal bone level were observed. CONCLUSIONS: These obtained results
      are probably because of joint pain, making it difficult to perform oral hygiene
      as well as the use of medication and general disease activity.

PMID- 18637045
TI  - Risk factors for injuries to maxillary permanent incisors and upper lip among
      schoolchildren in Dar es Salaam, Tanzania.
AB  - BACKGROUND: Dental trauma is common among children, and the maxillary permanent
      central incisors are the most often affected teeth. AIM: This study aimed to
      investigate the risk factors for injury to maxillary permanent incisors and the
      upper lip among Tanzanian schoolchildren aged 8-14 years. DESIGN: A cross
      sectional study involving 1119 children. The risk variables investigated included
      age, gender, lip competence, and overjet. The corresponding proportions of
      injuries and the relative risk (with 95% confidence interval) were calculated and
      tested by Fisher's exact test. Logistic regression was applied to ascertain the
      strength and direction of the association of the risk variables to injuries, and
      backward selection was used to test significant risk factors. RESULTS: About 24%
      of the children had trauma to maxillary incisors, 45% had incompetent lip whereas
      31% had increased overjet. Age, gender, overjet, and lip competence showed
      significant association with injuries to upper lip and maxillary incisors. Boys
      had sustained more injuries than girls, with a higher relative risk for luxation
      injuries. Enamel fracture was associated with overjet combined with lip
      competence, whereas enamel dentine fracture without pulp involvement was related
      to gender. Luxation injuries were associated with gender, tooth avulsion with
      overjet, and lip competence. Injury to the upper lip was associated with age.
      CONCLUSION: Male gender, increased overjet, and lip incompetence were the main
      risk factors of getting trauma to maxillary incisors, whereas age was the risk
      factor for injury to the upper lip.

PMID- 18637046
TI  - Caries prevalence and background factors in Swedish 4-year-old children - a 40
      year perspective.
AB  - BACKGROUND: Periodic and well-controlled studies of caries and background factors
      are important for organizing dental care and how prevention should be addressed.
      AIMS: The aims of this study were to compare data on caries prevalence and
      background factors in 4-year-old children from 2007 with data collected
      periodically between 1967 and 2002 with the same methods and criteria, and to
      compare immigrant and non-immigrant children concerning caries prevalence and
      background factors. DESIGN: A cross-sectional study in 4-year-old children living
      in Umea, northern Sweden (n = 218), was performed. Caries recordings included
      both cavitated and non-cavitated caries lesion, and bite-wing radiographs were
      used on indications. Data on oral hygiene, use of fluorides, general health, and
      medication and sugar consumption were collected using the same questions and
      questionnaire as in the previous studies. RESULTS: In 2007, 38% of the children
      displayed caries compared to 46% in 2002. The distribution of decayed, missing,
      or filled surfaces-primary teeth values was statistically significantly different
      in 2007 compared to 2002 (P < 0.05). The intake frequency of sugary between-meal
      products was generally lower, and toothbrushing frequency was higher in 2007
      compared with data from the 2002 study. In children with immigrant background,
      the frequency of toothbrushing was statistically significantly lower, and
      snacking was more common (P < 0.05). Sixteen per cent had immigrant background
      and 59% had caries compared to 32% in the rest of the cohort (P < 0.01).
      CONCLUSION: Important changes in caries prevalence of 4-year-old children have
      taken place since 2002 concurrently with a decreased intake of sugary between
      meal products and increased toothbrushing frequency. Immigrant background had a
      significant association with caries prevalence in 2007.

PMID- 18637047
TI  - Morphological aspects of dental hard tissues in primary teeth from preterm
      infants.
AB  - BACKGROUND: Preterm children with very low birth weight suffer from several
      neonatal and post-natal complications that may affect the mineralization of the
      teeth. Clinical studies have shown enamel aberrations in both dentitions. AIMS:
      The aims of this study were to describe enamel histo-morphology in primary teeth,
      and investigate the relationship between medical history and morphological
      appearance. DESIGN: Dental enamels in 44 exfoliated primary teeth, from 14
      children with a gestational age below 29 weeks and with a very low birth weight,
      were investigated, using polarized light microscopy (POLMI) and under a scanning
      electron microscope (SEM). RESULTS: The neonatal line was found in 1/3 of the
      sections located coronally of the crown. In the post-natal enamel, 31 teeth
      showed a degree of porosity higher than 5% with a varying extension. More than
      half of the teeth showed one or more increment lines. The SEM analysis confirmed
      the POLMI findings with irregular prisms covered with a structure-less film.
      CONCLUSIONS: Enamel from primary teeth of preterm children was found to have a
      high frequency of mineralization disturbances found in POLMI and SEM. The
      morphological features of the enamel from preterm children do not reflect the
      disturbances on general growth and development occurred during the neonatal
      period.

PMID- 18637048
TI  - Molar incisor hypomineralization in Hong Kong Chinese children.
AB  - BACKGROUND: Most prevalence studies on molar incisor hypomineralization (MIH)
      were carried out in European countries, and data from the East-Asian populations
      were lacking. AIM: This study aimed to investigate the prevalence of MIH in Hong
      Kong Chinese children. DESIGN: Since 2006, charting of teeth with MIH was
      included into the routine dental examination in a school dental clinic. The
      dental records of grade 6 primary school children who attended annual check-up in
      this clinic in 2006 were subsequently reviewed retrospectively. The records were
      selected for this study if the charting indicated that the children were affected
      by MIH. RESULTS: A total of 2635 records were reviewed and 73 cases of MIH were
      identified. The prevalence of MIH in this group of children was 2.8%. Their mean
      age was 12, and the male-to-female ratio was 1 : 1.2. The mean decayed, missing,
      or filled permanent teeth value of those affected was 1.5, which was higher than
      that of the general Hong Kong Chinese children aged 12 years old (0.8). A total
      of 192 teeth were affected. The most commonly affected teeth were permanent
      maxillary first molars, followed by mandibular first molars and maxillary central
      incisors. Dental fillings and fissure sealants were found in 52 (38%) and 65
      (47%) permanent first molars with hypomineralization, respectively. Medical
      histories were unremarkable in 60 children, whereas early childhood diseases were
      reported in 13 cases. CONCLUSIONS: The prevalence of MIH in the permanent
      dentition of Hong Kong Chinese children was 2.8%. Children with MIH showed higher
      caries experience in the permanent dentition than the general population of
      similar age.

PMID- 18637049
TI  - Microhabitat heterogeneity influences offspring sex allocation and spatial kin
      structure in possums.
AB  - 1. Sex allocation theory predicts that where dispersal is sex biased, the fitness
      consequences of producing male or female offspring are mediated by resource
      availability and maternal competitive ability. Females in poorer condition are
      expected to favour dispersing offspring to minimize resource competition with
      kin. Environmental heterogeneity may drive spatial variation in sex allocation
      through resource competition-related benefits to females and territory quality
      benefits to dispersing or philopatric offspring. 2. Here, we demonstrate that
      microhabitat heterogeneity can drive extremely fine-scale spatial heterogeneity
      in offspring sex allocation. Female bobucks (Trichosurus cunninghami) in
      temperate rainforest were more likely to produce male offspring than those in
      surrounding Eucalyptus forest. 3. A maternal physiological effect was identified,
      in that females of lower body mass were more likely to produce male offspring.
      This finding is consistent with resource competition predictions, in that smaller
      females are expected to have poorer competitive ability. 4. Genetic spatial
      autocorrelation analysis identified males as the more dispersing sex.
      Furthermore, overproduction of males by mothers in the rainforest habitat was
      geographically concordant with reduced philopatry, as inferred from spatial
      genetic analysis. This provides empirical validation of dispersal-related
      explanations of offspring sex allocation: that production of offspring of the
      dispersing sex minimizes the potential for resource competition with kin. 5.
      Spatial variation in dispersal via sex allocation responses to environmental
      heterogeneity can potentially contribute to spatial patterns in population
      dynamics.

PMID- 18637050
TI  - Striate palmoplantar keratoderma in a patient with Rubinstein-Taybi syndrome.

PMID- 18637051
TI  - Quality assessment of perinatal and infant postmortem examinations in Turkey.
AB  - An autopsy examination is important in identifying the cause of death and as a
      means of auditing clinical and forensic practice; however, especially in
      perinatal and infantile age groups determining the cause of death leads to some
      difficulties in autopsy practice. In this study, 15,640 autopsies recorded during
      the years 2000-2004 in the Mortuary Department of the Council of Forensic
      Medicine were reviewed. Autopsy findings of 510 cases between 20 completed weeks
      of gestation and 1 year of age were analyzed retrospectively. The quality of each
      necropsy report was assessed using a modification of the system gestational age
      assessment described by Rushton, which objectively scores aspects identified by
      the Royal College of Pathologists as being part of a necropsy. According to their
      ages, the cases were subdivided into three groups. Intrauterine deaths were 31%
      (158 cases), neonatal deaths were 24% (123 cases), and infantile deaths were 45%
      (229 cases) of all cases. Scores for the quality of the necropsy report were
      above the minimum acceptable score with 44% in intrauterine, 88% in neonatal and
      infantile deaths.

PMID- 18637052
TI  - Potential for cost-savings in the care of hospitalized low-risk community
      acquired pneumonia patients in China.
AB  - BACKGROUND: The cost of treating community-acquired pneumonia (CAP) in China is a
      heavy economic burden for the society. OBJECTIVE: To investigate the costs of
      hospitalization of low-risk CAP patients and how hospitalization costs can be
      reduced through proper usage of hospital resources. METHODS: Two hundred thirty
      six patients with low-risk CAP who were hospitalized between January 2000 and
      December 2005 in a 1161-bed tertiary care teaching hospital were included in a
      retrospective cohort study. Their hospitalization costs and antibiotic therapy
      were analyzed. General linear model was utilized to determine correlative
      variables associated with total hospital costs. RESULTS: The median length of
      hospital stay was 12 days and the median duration of intravenous (IV) antibiotic
      therapy was 10 days, they were correlated significantly (P = 0.000, r = 0.81).
      The median total hospital cost was $556.50 (mean $705.60), of which 48.9% was for
      drugs, 21.9% for laboratory tests, 8.6% for radiology, 6.5% for medical staff,
      6.3% for hospital beds, and 5.3% for examination. General linear model analysis
      determined that duration of IV antibiotic therapy, Pneumonia Severity Index
      class, age, and initial empirical antibiotic therapy failure were correlative
      factors of total hospital costs. Pathogens were identified in 106 patients
      (44.9%), Mycoplasma pneumoniae was the most common pathogen (19.9%), followed by
      Streptococcus pneumoniae (8.5%), and Haemophilus influenza (5.5%). The majority
      of patients accepted initial empirical beta-lactam (37.3%) or fluoroquinolone
      (30.9%) monotherapy, the empirical treatment failure rates were 20.5% and 5.5%,
      respectively. CONCLUSIONS: Efforts to reduce duration of IV antibiotic therapy
      will have the most profound effect on reducing total hospital costs of low-risk
      CAP. The atypical pathogens should be considered for initial empirical
      antibiotics in low-risk CAP therapy in China.

PMID- 18637053
TI  - Prediction value of model for end-stage liver disease scoring system on prognosis
      in patients with acute-on-chronic hepatitis B liver failure after plasma exchange
      and lamivudine treatment.
AB  - BACKGROUND AND AIM: We used the model for end-stage liver disease (MELD) scoring
      system to predict the 3-month prognosis of patients with acute-on-chronic liver
      failure (ACLF) after plasma exchange (PE) and lamivudine treatment, and studied
      the predictive factors on the prognosis of patients. METHODS: A total of 280
      patients treated with lamivudine were randomly divided into PE and control
      groups. The relationship between mortality and influential factors of patients
      was studied by univariate and multivariate analysis. RESULTS: The mortality
      (49.4%) of patients in the PE group with a MELD score from 30 to 40 was lower
      than that (86.1%) of the control group (chi(2) = 24.546, P < 0.01). The total
      bilirubin (TBIL) rebound rate of the dead group was significantly higher than
      that of the survival group (P < 0.01). Univariate analysis showed that mortality
      was significantly related to age (P = 0.003), treatment method (P = 0.000), TBIL
      (P = 0.010), MELD score (P = 0.001), international normalised ratio (P = 0.014),
      pretreatment HBV-DNA load (P = 0.000), decline of hepatitis B virus (HBV)-DNA
      load during therapy (P = 0.013), encephalopathy (P = 0.019), and hepatorenal
      syndrome (P = 0.026). In multivariate analysis, MELD scores of 30-40, treatment
      method (P = 0.003), pretreatment HBV-DNA load (P = 0.009), decline of HBV-DNA
      load during therapy (P = 0.016), and encephalopathy (P = 0.015) were independent
      predictors of mortality; for MELD scores above 40, only the MELD score (P =
      0.012) was an independent predictive. CONCLUSIONS: PE significantly decreased the
      mortality of patients with a MELD score of 30-40. For ACLF patients with a MELD
      score of 30-40, a low viral load pretreatment and quick decline of HBV-DNA load
      are good predictors for the survival with PE and lamivudine treatment.

PMID- 18637054
TI  - Evaluation of the prognostic powers of various tumor status grading scales in
      patients with hepatocellular carcinoma.
AB  - BACKGROUNDS AND AIM: Several tumor status grading scales are available for
      patients with hepatocellular carcinoma (HCC), which include several tumor-node
      metastasis (TNM) systems and clinical staging systems, such as Cancer of the
      Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC). This study
      was performed to analyze the prognostic powers of these tumor status grading
      systems in HCC. METHODS: A retrospective cohort of 499 consecutive patients with
      HCC was included. The tumor statuses of all patients were classified according to
      several TNM systems (sixth version of the American Joint Committee on Cancer,
      fourth version of the Liver Cancer Study Group of Japan [LCSGJ], and the United
      Network for Organ Sharing UNOS system) and according to the tumor status grading
      scales of the BCLC (TBCLC) and CLIP (TCLIP) systems. Prognostic powers were
      quantified using a linear trend chi(2)-test, c-index, and the likelihood ratio
      (LHR) chi(2)-test, and correlated using Cox's regression model adjusted using the
      Akaike information criterion (AIC). RESULTS: Of the TNM systems, the fourth LCSGJ
      system had the highest prognostic power (LHR chi(2) = 7.20, AIC = 4803.02).
      However, when TBCLC and TCLIP were included in the analysis, TCLIP showed the
      best predictive power (LHR chi(2) = 29.52, AIC = 4799.82). CONCLUSION: TCLIP had
      best predictive power in HCC patients of the various tumor staging systems
      examined. To improve prognostic power, factors other than tumor burden, such as
      tumor behavior, should be included in the tumor status grading system for HCC.

PMID- 18637055
TI  - Mechanism for gastric cancer development by Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) infection plays a crucial role in the development
      of gastric cancer. There are two major pathways for the development of gastric
      cancer by H. pylori infection: the indirect action of H. pylori on gastric
      epithelial cells through inflammation, and the direct action of the bacteria on
      epithelial cells through the induction of protein modulation and gene mutation.
      Both pathways work together to promote gastric carcinogenesis.

PMID- 18637056
TI  - Does hyaluronic acid stimulate tumor growth after endoscopic mucosal resection?
AB  - BACKGROUND AND AIM: A submucosal injection of sodium hyaluronate is widely used
      for mucosal elevation in endoscopic mucosal resection (EMR) or endoscopic
      submucosal dissection procedures; however, the oncologic safety of sodium
      hyaluronate remains unknown. Hyaluronate is the main ligand for CD44 and this
      interaction was reported to promote tumor progression in in vitro or animal
      studies. This study aimed to evaluate the effects of sodium hyaluronate on tumor
      growth after EMR for gastrointestinal cancers. METHODS: The study included 18
      consecutive patients who underwent surgery for locally-recurrent or remnant
      gastrointestinal cancers after EMR from January 2001 to December 2006. The
      immunohistochemical expression levels of Ki-67, CD44, ErbB2, and epidermal growth
      factor receptor (EGFR) were evaluated in the primary tumor tissue and the
      recurrent tumor. The protein expression in recurrent or remnant lesions was also
      compared between the sodium hyaluronate group and non-sodium hyaluronate group.
      RESULTS: Sodium hyaluronate was used in nine of 14 cases with EMR for gastric
      cancers and in one of four cases for colon cancers. The time to operation after
      EMR was 133 days (5-687 days). An analysis of the immunohistochemical expression
      levels between primary and recurrent or remnant tumors showed no significant
      differences in the expression levels of Ki-67, CD44, ErbB2, and EGFR with or
      without sodium hyaluronate. CONCLUSIONS: We found no evidence that sodium
      hyaluronate stimulates the growth of remnant tumors after EMR.

PMID- 18637057
TI  - Model consisting of ultrasonographic and simple blood indexes accurately identify
      compensated hepatitis B cirrhosis.
AB  - BACKGROUND AND AIM: Several models for significant fibrosis or cirrhosis have
      been introduced for hepatitis C, but are seldom for hepatitis B. The present
      study retrospectively evaluates the relationship between ultrasonography, blood
      tests, and fibrosis stage, and constructs a model for predicting compensated
      cirrhosis. METHODS: A total of 653 patients with chronic hepatitis B who
      underwent liver biopsies, ultrasonographic scanning, and routine blood tests were
      retrospectively analyzed. The patients were divided into the model set and
      validation set. Blood tests and ultrasonographic indexes were analyzed
      statistically. An ultrasonographic scoring system consisting of liver parenchyma,
      gallbladder, hepatic vessel, and splenomegaly was introduced. RESULTS: There were
      significant differences between cirrhosis and other fibrosis stages in
      ultrasonographic indexes of liver parenchyma, gallbladder, hepatic vessel, and
      splenomegaly. Ultrasonographic scores were significantly different between F4 and
      other fibrosis, and significantly correlated with fibrosis stage. Apart from
      alanine aminotransferase and alkaline phosphatase, blood tests and patients' age
      were correlated with fibrosis, and were significantly different between patients
      with and without cirrhosis. The model for cirrhosis indexes consisting of
      ultrasonographic score, patient's age, and variables, including platelet,
      albumin, and bilirubin predicted cirrhosis with area under receiver-operator
      curve of 0.907 in the model set and 0.849 in the validation set. Using proper cut
      off values, nearly 81% patients could be accurately assessed for the absence or
      presence of cirrhosis. CONCLUSION: The model consisting of ultrasonographic
      score, patients' age, blood variables of platelet, albumin, and bilirubin can
      identify hepatitis B cirrhosis with a high degree of accuracy. The application of
      this model would greatly reduce the number of biopsies.

PMID- 18637058
TI  - Ruggero Oddi: 120 years after the description of the eponymous sphincter: a story
      to be remembered.
AB  - This article presents a short account of theories, methods, and experimental data
      formulated and carried out 120 years ago, by Ruggero Oddi, then a 4th-year
      student in medicine, about the identification of the common bile duct sphincter.
      A historical picture emerges which leads us to think that Oddi not only
      discovered the bile duct sphincter, but also described bile duct dilation after
      cholecystectomy and performed biliary manometry for the first time. The role of
      serendipity and the almost unknown contribution of Arturo Marcacci, Oddi's
      "maestro" are also mentioned.

PMID- 18637059
TI  - Etiology and outcome of acute liver failure: retrospective analysis of 50
      patients treated at a single center.
AB  - BACKGROUND AND AIM: Acute liver failure (ALF) remains a devastating disease
      carrying considerable mortality. Since deceased donor liver transplantation is
      rarely performed in Japan, the artificial liver support system (ALS) and living
      donor liver transplantation (LDLT) are the main modalities used for treatment of
      ALF. The aim of this study was to analyze the outcome of ALF patients and to
      evaluate therapies for ALF according to etiology. METHODS: Fifty consecutive
      patients with ALF were treated between January 1990 and December 2006. Prior to
      1997, patients received ALS only. After 1997, ALS and/or LDLT were applied. LDLT
      was performed in 10 patients. RESULTS: Four of 15 (27%) pre-1997 ALF patients
      survived, and 16 of 35 (46%) post-1997 ALF patients survived, including eight who
      underwent LDLT. The causes of ALF were acute hepatitis B virus (HBV) infection in
      18%, severe acute exacerbation (SAE) of chronic HBV infection in 18%, autoimmune
      hepatitis (AIH) in 8%, and cryptogenic hepatitis in 44%. In total, 67% of the
      patients with ALF caused by acute HBV infection and AIH were cured without LDLT;
      only 11% of patients with ALF caused by SAE of HBV and 24% of cryptogenic
      hepatitis were successfully treated without LDLT. Notably, 80% of patients with
      cryptogenic hepatitis who underwent LDLT survived. CONCLUSION: Since 1997, the
      survival rate of ALF patients has increased, mainly due to the introduction of
      LDLT. Liver transplantation should be performed especially in patients with ALF
      caused by SAE of HBV and cryptogenic hepatitis.

PMID- 18637060
TI  - New paradigms for the treatment of chronic hepatitis B.
AB  - The main goals of chronic hepatitis B treatment should be the long-term
      suppression of viral replication to minimize disease progression and the risk for
      the development of hepatocellular carcinoma. Treatment end-points, depending on
      surrogate markers alone, in particular hepatitis B e-antigen seroconversion, may
      not be ideal for patients who acquire the disease early in life. Currently
      available drugs include interferons and oral nucleoside/nucleotide analogs.
      Although interferon therapy provides a finite treatment period, a significant
      proportion of patients may not respond, and long-term outcome is inconclusive.
      Long-term efficacy has been demonstrated for both lamivudine and adefovir.
      However, prolonged nucleoside/nucleotide analog therapy is associated with the
      emergence of drug-resistant mutations. Therefore, nucleoside/nucleotide analogs
      with a high genetic barrier and potent antiviral activity, such as entecavir,
      should be used to reduce the chance of developing drug-resistant mutations. Drugs
      with a low genetic barrier, including lamivudine and telbivudine, should be used
      in conjunction with early testing for antiviral response. This can predict
      favorable outcomes in the long term. The early detection of drug-resistant
      mutations should prompt clinicians to either add or switch to another agent with
      a different drug-resistance profile. There are currently no treatment models in
      the use of combination or sequential therapy in treatment-naive patients. To
      date, long-term treatment appears to be the most effective option. Despite recent
      advances made with better understanding on the natural history of chronic
      hepatitis B infection and with newer antiviral drugs available, challenges remain
      with respect to treatment criteria, treatment end-points, and duration of
      treatment.

PMID- 18637061
TI  - Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori
      infection by 7-day triple therapy with regular proton pump inhibitor dosage.
AB  - BACKGROUND AND AIM: Proton pump inhibitors (PPI) are mainly metabolized by
      cytochrome P450 2C19 (CYP2C19) in the liver. We investigated whether the CYP2C19
      genotype plays a role in the eradication rate of Helicobacter pylori (H. pylori)
      infection in patients receiving pantoprazole- or esomeprazole-based triple
      therapy. METHODS: A total of 327 patients infected with H. pylori were treated
      with either pantoprazole or esomeprazole, plus amoxicillin and clarithromycin for
      7 days. The presence of the CYP2C19 genotype was determined by pyrosequencing.
      RESULTS: The overall H. pylori eradication rate was 85%; 82.6% for the PAC
      regimen, and 88.3% for the EAC regimen; the differences were not statistically
      significant. The overall eradication rate in the poor metabolizer groups (PM) was
      significantly higher than in the extensive metabolizer groups (EM) (97.4% vs
      83.3%; P = 0.016). The eradication rates in the EM and PM groups were 80.8% and
      95.7% for the PAC regimen and 86.8% and 100% for the EAC regimen, respectively.
      CONCLUSION: The results of this study suggest that the CYP2C19 genotype status
      may play a role in the H. pylori eradication rate in patients receiving
      pantoprazole or esomeprazole-based triple therapy.

PMID- 18637062
TI  - Behaviour problems and adults with Down syndrome: childhood risk factors.
AB  - BACKGROUND: Studies of people with intellectual disability suggest that several
      individual characteristics and environmental factors are associated with
      behaviour disorder. To date there are few studies looking at risk factors within
      specific syndromes and the relationship between early risk markers and later
      behaviour disorder. The key aim of the study was to determine if childhood risk
      factors were predictors of severe behaviour disorder in young adults with Down
      syndrome. MATERIALS AND METHODS: A longitudinal cohort study of 50 people with
      Down syndrome was assessed with the same behavioural measure used in both
      childhood and adult life. The early risk factors which were assessed included
      childhood functioning, childhood psychopathology and early family environment as
      determined by measures of parental mental health, quality of parental marriage
      and social background. RESULTS: Childhood psychopathology and functioning were
      associated with severe behaviour disorder in adult life whereas childhood family
      environment was not. CONCLUSIONS: Children with Down syndrome at risk for severe
      behaviour disorder in adult life may be identified in childhood and appropriate
      interventions offered to reduce their risk.

PMID- 18637063
TI  - Pretreatment alanine transaminase level may not be the most important predictor
      of HBeAg loss in the older patient.
AB  - BACKGROUND: Elevated pretreatment alanine aminotransferase (ALT) over two times
      the upper limit of normal reference range has been accepted as a marker for
      predicting HBeAg loss and an indicator for initiating antiviral therapy.
      Recently, several opinions argued that in patients aged over 40 years, the
      treatment should be started if they have elevated serum hepatitis B virus (HBV)
      DNA without elevated ALT. However, initiating treatment in these patients might
      be argued against by the concept that the rate of HBeAg loss depends on the
      pretreatment ALT. AIM: This study was conducted to investigate the usefulness of
      pretreatment ALT in predicting HBeAg loss in patients aged over 40 years under
      lamivudine treatment. METHODS: We retrospectively analyzed 820 HBeAg-positive
      patients treated with lamivudine. The patients with hepatocellular carcinoma at
      or after initiating the lamivudine treatment and patients with evident liver
      cirrhosis were excluded. Three hundred fifty-five patients met the criteria and
      were divided into two groups: </=40 years of age (Group 1) and >40 years of age
      (Group 2). RESULTS: Analysis using the Kaplan-Meier method and the log rank test
      showed that the cumulative rate of HBeAg loss was not different in the two
      groups. Multivariate modelling indicated that an elevated pretreatment ALT level
      was a predictor of HBeAg loss in Group 1 (P<0.05), whereas it failed to act as a
      predictor in Group 2. CONCLUSION: Antiviral therapy might not need to be deferred
      until the ALT level increases in order to enhance the chance of HbeAg loss in HBV
      DNA-(+) patients aged over 40 years.

PMID- 18637064
TI  - Non-invasive assessment of liver fibrosis by stiffness measurement in patients
      with chronic hepatitis B.
AB  - BACKGROUND: The need for new non-invasive tools to assess liver fibrosis in
      chronic liver diseases has been largely advocated. Liver stiffness measurement
      (LSM) using transient elastography (FibroScan), Echosens) has been shown to be
      correlated to liver fibrosis in various chronic liver diseases. This study aims
      to assess its diagnosis accuracy in patients with chronic hepatitis B. PATIENTS
      AND METHODS: We prospectively enrolled 202 patients with chronic hepatitis B in a
      multicentre study. Patients underwent liver biopsy (LB) and LSM. METAVIR and
      Ishak liver fibrosis stages were assessed by two pathologists. RESULTS: LSM or LB
      was considered unreliable in 29 patients. Statistical analysis was conducted in
      173 patients. LSM was significantly (P<0.001) correlated with METAVIR (r=0.65)
      and Ishak fibrosis stage (0.65). The area under receiver-operating characteristic
      curves were 0.81 (95% confidence intervals, 0.73-0.86) for F>/=2, 0.93 (0.88
      0.96) for F>/=3 and 0.93 (0.82-0.98) for F=4. Optimal LSM cut-off values were 7.2
      and 11.0 kPa for F>/=2 and F=4, respectively, by maximizing the sum D of
      sensitivity and specificity, and 7.2 and 18.2 kPa by maximizing the diagnosis
      accuracy. CONCLUSION: In conclusion, LSM appears to be reliable for detection of
      significant fibrosis or cirrhosis in HBV patients and cut-off values are only
      slightly different from those observed in HCV patients.

PMID- 18637065
TI  - A 1H nuclear magnetic resonance-based metabonomic approach for grading hepatic
      encephalopathy and monitoring the effects of therapeutic hypothermia in rats.
AB  - BACKGROUND: There are no good biomarkers for grading hepatic encephalopathy (HE)
      and monitoring the effectiveness of therapeutic measures. METHODS: We applied
      (1)H nuclear magnetic resonance (NMR)-based metabonomics of brain samples
      obtained from acute liver failure rats sacrificed after ligation of the hepatic
      artery (at 6 h, precoma and coma stages), sham-operated controls and mild
      hypothermia (35 degrees C) for 6 or 15 h as a therapeutic measure. RESULTS:
      Partial least square discriminant analysis established a classification model
      that scored the severity of encephalopathy. Animals treated with hypothermia did
      not develop manifestations of encephalopathy and were graded accordingly using
      the NMR-based metabonomic approach. Hypothermic animals showed lower levels of
      alanine and lactate as well as higher levels of N-acetylaspartate and myo
      inositol compared with normothermic animals. The course of metabolic
      deterioration was more rapid in the brainstem than in the cortex. CONCLUSION:
      Metabonomic analysis is capable of grading HE, detecting regional differences and
      monitoring the protective effects of hypothermia. This approach elucidates
      differences of brain energetic metabolism and compensatory osmotic response to
      explain the effects of hypothermia.

PMID- 18637066
TI  - Optimal co-allocation of carbon and nitrogen in a forest stand at steady state.
AB  - Nitrogen (N) is essential for plant production, but N uptake imposes carbon (C)
      costs through maintenance respiration and fine-root construction, suggesting that
      an optimal C:N balance can be found. Previous studies have elaborated this
      optimum under exponential growth; work on closed canopies has focused on foliage
      only. Here, the optimal co-allocation of C and N to foliage, fine roots and live
      wood is examined in a closed forest stand. Optimal co-allocation maximizes net
      primary productivity (NPP) as constrained by stand-level C and N balances and the
      pipe model. Photosynthesis and maintenance respiration increase with foliar
      nitrogen concentration ([N]), and stand-level photosynthesis and N uptake
      saturate at high foliage and fine-root density. Optimal NPP increases almost
      linearly from low to moderate N availability, saturating at high N. Where N
      availability is very low or very high, the system resembles a functional balance
      with a steady foliage [N]; in between, [N] increases with N availability. Carbon
      allocation to fine roots decreases, allocation to wood increases, and allocation
      to foliage remains stable with increasing N availability. The predicted
      relationships between biomass density and foliage [N] are in reasonable agreement
      with data from coniferous stands across Finland. All predictions agree with our
      qualitative understanding of N effects on growth.

PMID- 18637067
TI  - Leaf hydraulic conductivity and photosynthesis are genetically correlated in an
      annual grass.
AB  - Comparative studies suggest that a positive correlation between xylem water
      transport and photosynthesis is adaptive. A requirement for the adaptive
      evolution of coordination between xylem and photosynthetic functions is the
      presence of genetic variation and covariation for these traits within
      populations. Here it was determined whether there was genetic variation and
      covariation for leaf blade hydraulic conductivity (K(W)), photosynthetic rate
      (A), stomatal conductance (g(s)), and time to flowering in a population of
      recombinant inbred lines of Avena barbata, a Mediterranean annual grass.
      Significant (P < 0.05) broad-sense heritabilities (H(2)) were detected for K(W)
      (H(2) = 0.33), A (H(2) = 0.23) and flowering time (H(2) = 0.62), but not for
      g(s). Significant positive genetic covariation between A and K(W) was also
      observed. There was no other genetic covariation among traits. The first evidence
      of genetic variation for K(W) within a species was obtained. These results also
      indicate that there is a genetic basis for the positive association between xylem
      water transport and photosynthesis. The presence of significant genetic variation
      and covariation for these traits in natural populations would facilitate
      correlated evolution between xylem and leaf functions.

PMID- 18637068
TI  - Monocyte-derived dendritic cells from HCV-infected patients transduced with an
      adenovirus expressing NS3 are functional when stimulated with the TLR3 ligand
      poly(I:C).
AB  - Dendritic cells (DC) transfected with an adenovirus encoding hepatitis C virus
      (HCV) NS3 protein (AdNS3) induce potent antiviral immune responses when used to
      immunize mice. However, in HCV infected patients, controversial results have been
      reported regarding the functional properties of monocyte-derived DC (MoDC), a
      cell population commonly used in DC vaccination protocols. Thus, with the aim of
      future vaccination studies we decided to characterize MoDC from HCV patients
      transfected with AdNS3 and stimulated with the TLR3 ligand poly(I:C). Phenotypic
      and functional properties of these cells were compared with those from MoDC
      obtained from uninfected individuals. PCR analysis showed that HCV RNA was
      negative in MoDC from patients after the culture period. Also, phenotypic
      analysis of these cells showed lower expression of CD80, CD86, and CD40, but
      similar expression of HLA-DR molecules as compared to MoDC from uninfected
      individuals. Functional assays of MoDC obtained from patients and controls showed
      a similar ability to activate allogeneic lymphocytes or to produce IL-12 and IL
      10, although lower IFN-alpha levels were produced by cells from HCV patients
      after poly(I:C) stimulation. Moreover, both groups of MoDC induced similar
      profiles of IFN-gamma and IL-5 after stimulation of allogeneic T-cells. Finally,
      migration assays did not reveal any difference in their ability to respond to
      CCL21 chemokine. In conclusion, MoDC from HCV patients are functional after
      transduction with AdNS3 and stimulation with poly(I:C). These findings suggest
      that these cells may be useful for therapeutic vaccination in chronic HCV
      infection.

PMID- 18637069
TI  - Optimal dose of peginterferon and ribavirin for treatment of chronic hepatitis C.
AB  - Chronic hepatitis C affects 170 million people worldwide, including up to 4
      million people in the United States. The current standard of care therapy with
      pegylated interferon (PEG-IFN) and ribavirin (RBV) while highly successful in
      patients with genotype 2 and 3 infection, allows for sustained virologic response
      in 42-46% of treatment-naive genotype 1 patients, comprising about 70% of cases
      of chronic hepatitis C in the USA. While awaiting approval of Specifically
      Targeted Antiviral Therapy for HCV (STAT-C) agents, which will require the
      completion of additional clinical trials, it is important to optimize the dose
      and duration of currently available treatment modalities, namely PEG-IFN and RBV,
      for treatment of CHC. Results of several recent trials evaluating optimal dosing
      of RBV and higher than standard dosing of PEG-IFN in treatment-naive genotype 1
      patients, as well as data from retreatment trials with "induction" doses of PEG
      IFN or high-dose RBV in prior non-responders to IFN-based therapy will be
      reviewed here. The possibility of shorter duration of therapy for genotype 2 and
      3 patients based on recent publications and presentations will be discussed as
      well.

PMID- 18637070
TI  - Response to pegylated interferon plus ribavirin in HIV-infected patients with
      chronic hepatitis C due to genotype 4.
AB  - SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated
      interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies
      merge these two genotypes when assessing virological response. However, in most
      trials the HCV genotype 4 population is rather small, and conclusions are mainly
      derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with
      HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and
      ROMANCE, conducted respectively in Spain and Italy, were retrospectively
      analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU /
      mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week
      12 (early virological response, EVR) were all assessed as predictors of sustained
      virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median
      age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA
      <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver
      fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid
      virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using
      intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75
      (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate
      analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01
      0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently
      associated with SVR. This is the largest series of HIV-infected patients with
      chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and
      the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients
      should be considered as difficult to treat population. Baseline serum HCV-RNA and
      EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

PMID- 18637071
TI  - Natural killer cells suppress full cycle HCV infection of human hepatocytes.
AB  - The role of natural killer (NK) cells in controlling hepatitis C virus (HCV)
      infection and replication has not been fully delineated. We examined NK cell
      mediated noncytolytic effect on full cycle HCV infection of human hepatocytes.
      Human hepatocytes (Huh7.5.1 cells) co-cultured with NK cells or treated with
      supernatants (SN) from NK cells cultures had significantly lower levels of HCV
      RNA and protein than control cells. This NK cell-mediated anti-HCV activity could
      be largely abolished by antibody to interferon-gamma (IFN-gamma). The
      investigation of the mechanisms for NK cell-mediated anti-HCV activity showed
      that NK SN-treated hepatocytes expressed higher levels of IFN-alpha/beta than the
      control cells. NK SN also enhanced IFN regulatory factor-3 and 7 expression in
      the hepatocytes. In addition, NK SN enhanced the expression of signal transducer
      and activator of transcription 1 and 2, the nuclear factors that are essential
      for the activation of IFN-mediated antiviral pathways. These data provide direct
      evidence at cellular and molecular levels that NK cells have a key role in
      suppressing HCV infection of and replication in human hepatocytes.

PMID- 18637072
TI  - Active intravenous drug use during chronic hepatitis C therapy does not reduce
      sustained virological response rates in adherent patients.
AB  - SUMMARY: Reluctance has been expressed about treating chronic hepatitis C in
      active intravenous (IV) drug users (IDUs), and this is found in both
      international guidelines and routine clinical practice. However, the medical
      literature provides no evidence for an unequivocal treatment deferral of this
      risk group. We retrospectively analyzed the direct effect of IV drug use on
      treatment outcome in 500 chronic hepatitis C patients enrolled in the Swiss
      Hepatitis C Cohort Study. Patients were eligible for the study if they had their
      serum hepatitis C virus (HCV) RNA tested 6 months after the end of treatment and
      at least one visit during the antiviral therapy, documenting the drug use status.
      Five hundred patients fulfilled the inclusion criteria (199 were IDU and 301
      controls). A minimum exposure to 80% of the scheduled cumulative dose of
      antivirals was reached in 66.0% of IDU and 60.5% of controls (P = NS). The
      overall sustained virological response (SVR) rate was 63.6%. Active IDU reached a
      SVR of 69.3%, statistically not significantly different from controls (59.8%). A
      multivariate analysis for treatment success showed no significant negative
      influence of active IV drug use. In conclusion, our study shows no relevant
      direct influence of IV drugs on the efficacy of anti-HCV therapy among adherent
      patients.

PMID- 18637073
TI  - Diagnosis of acute hepatitis C virus infection and estimated incidence in low-
      and high-risk English populations.
AB  - The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward;
      few people exhibit clinical symptoms and genome/antigen detection techniques do
      not indicate when infection had occurred. Here, a strategy to detect HCV RNA in
      the absence of antibody ('window-period') for diagnosis of acute infection is
      assessed. The sentinel surveillance of hepatitis testing study was used to
      retrospectively identify anti-HCV negative samples from high-risk individuals
      (2002-2003), for testing singly for HCV RNA. Additional samples were identified
      prospectively (2005) and tested in pools for HCV RNA. Positive samples were
      genotyped. Incidence and costs of adopting the pooling strategy were estimated.
      In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive,
      anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five
      positive pools identified four confirmed HCV RNA positive patients (one false
      positive). Estimated incidence was 12.9 per 100 person-years in injecting drug
      users (IDUs) (retrospective study) and 3.7 per 100 person-years among
      drug/alcohol services and prison attendees (prospective study). Estimated costs
      were pound 850 per positive sample, in areas of higher risk. The yield from a
      window-period strategy depends upon the population tested. Pooled HCV RNA testing
      of anti-HCV negative samples from the current IDUs is realistic and relatively
      inexpensive to identify recently infected individuals.

PMID- 18637074
TI  - The cost-effectiveness of screening and treatment for hepatitis C in prisons in
      England and Wales: a cost-utility analysis.
AB  - Prisoners have a high prevalence of hepatitis C virus (HCV) infection compared
      with the general population in England and Wales and in many locations throughout
      the world. This is because of large numbers of injecting drug users that engage
      in behaviours likely to transmit HCV being present within prison populations. It
      is, therefore, suggested that prison may be an appropriate location for HCV
      screening and treatment to be administered. Using cost-utility analysis, this
      study considers the costs and benefits of administering a single round of
      screening on reception into prison to all individuals followed by possible later
      screening in the community and comparing this to individuals who may only be
      tested and treated in the community at a later date. The cost/QALY of one round
      of prison testing and treatment was found to be 54,852 pounds sterling, although
      probabilistic sensitivity analysis showed extensive uncertainty about this
      estimate. One-way sensitivity analysis revealed the importance of the parameters
      describing the progression of chronic HCV and the discount rates. While the
      results presented here at baseline would suggest that screening and treatment for
      HCV in prisons is not cost-effective, these results are subject to much
      uncertainty. The importance of the rates describing the progression of chronic
      HCV on the cost-effectiveness of this intervention has been demonstrated and this
      suggests that future work should be undertaken to gain further insight into the
      rates that individuals progress to the later stages of chronic HCV infection.

PMID- 18637075
TI  - Hepatocellular carcinoma in long-term sustained virological responders following
      antiviral combination therapy for chronic hepatitis C.
AB  - Antiviral treatment results in a sustained virologic response (SVR) in 50-75% of
      patients with chronic hepatitis C. Long-term follow up studies have observed
      ongoing SVR in the overwhelming majority of them. Thus chronic hepatitis C is
      considered 'cured' if an SVR is achieved. Consequently, it is expected that in
      sustained virologic responders long-term complications of hepatatic C virus (HCV)
      related chronic liver disease including hepatocellular carcinoma are eliminated
      or have a decreased incidence. We report on five patients (three from Austria,
      two from USA) who developed hepatocellular carcinoma during follow up (3-6 years)
      after achieving SVR. During follow up and at diagnosis all were HCV-RNA neg. None
      of the patients had other liver diseases. One patient presented with bilateral
      adrenal metastasis, the remaining four with large hepatic tumours. Three patients
      were noncirrhotic at the start of treatment at the time of tumour diagnosis.
      Successful antiviral treatment in HCV patients does not prevent development of
      hepatocellular carcinoma even in non-cirrhotic livers. Long-term follow up of
      patients with SVR is mandatory and should include surveillance for hepatocellular
      carcinoma.

PMID- 18637076
TI  - Correlation of serum ribavirin concentration with pretreatment renal function
      estimates in patients with chronic hepatitis C receiving combination antiviral
      therapy with peginterferon and ribavirin.
AB  - Serum ribavirin concentration is an important factor in antiviral therapy in
      combination with peginterferon (PEG-IFN) and ribavirin for patients with chronic
      hepatitis C in terms of both beneficial and adverse effects. We evaluated whether
      the serum ribavirin concentration can be predicted on the basis of renal function
      estimates. Serum creatinine and cystatin C concentrations were measured at the
      start of treatment in a total of 148 patients with chronic hepatitis C who
      underwent combination PEG-IFN and ribavirin therapy. Creatinine clearance (CrCl)
      and total clearance of ribavirin (CL/F) were calculated on the basis of the serum
      creatinine level. The glomerular filtration rate was calculated with two
      different formulae on the basis of the serum cystatin C level. These values were
      compared with serum ribavirin concentrations 4 weeks after the start of therapy.
      The cystatin C level increased with the progression of liver fibrosis, whereas
      the creatinine level was constant regardless of the degree of liver fibrosis.
      Significant correlation was not observed between the serum ribavirin
      concentration and serum creatinine level, cystatin C level, or calculated renal
      function estimates. However, significant correlation was found between the serum
      ribavirin concentration and CrCl and CL/F in patients who were given ribavirin
      >800 mg/day. Overall, renal function estimates do not correlate with the serum
      ribavirin concentration in Japanese patients with chronic hepatitis C who undergo
      combination PEG-IFN and ribavirin therapy. Serum creatinine-based renal function
      estimates might be predictive for the serum ribavirin concentration only in
      patients with a daily ribavirin intake of 800 mg or more.

PMID- 18637077
TI  - Human dendritic cells pulsed with specific lipopeptides stimulate autologous
      antigen-specific T cells without the addition of exogenous maturation factors.
AB  - SUMMARY: Serum-free culture conditions to generate immature human monocyte
      derived DC (Mo-DC) were optimized, and the parameters that influence their
      maturation after exposure to lipopeptides containing CD4(+) and CD8(+) T-cell
      epitopes were examined. The lipopeptides contained a single CD4(+) helper T-cell
      epitopes, one of a number of human leucocyte antigen (HLA)-A2-restricted
      cytotoxic T-cell epitope and the lipid Pam2Cys. To ensure complete maturation of
      the Mo-DC, we examined (i) the optimal lipopeptide concentration, (ii) the
      optimal Mo-DC density and (iii) the appropriate period of exposure of the Mo-DC
      to the lipopeptides. The results showed that a high dose of lipopeptide (30
      microm) was no more efficient at upregulating maturation markers on Mo-DC than a
      low dose (6 microm). There was an inverse relationship between Mo-DC
      concentration and the mean fluorescence intensity of maturation markers. In
      addition, at the higher cell concentrations, the chemotactic capacity of the Mo
      DC towards a cognate ligand, CCL21, was reduced. Thus, high cell concentrations
      during lipopeptide exposure were detrimental to Mo-DC maturation and function.
      The duration of exposure of Mo-DC to the lipopeptides had little effect on
      phenotype, although Mo-DC exposed to lipopeptides for 48 rather than 4 h showed
      an increased ability to stimulate autologous peripheral blood mononuclear cells
      to release interferon-gamma in the absence of exogenous maturation factors. These
      findings reveal conditions for generating mature antigen-loaded DC suitable for
      targeted immunotherapy.

PMID- 18637078
TI  - Where are people being tested for anti-HCV in England? Results from sentinel
      laboratory surveillance.
AB  - SUMMARY: Many people infected with hepatitis C virus (HCV) are unaware of their
      infection and are, therefore. potentially infectious to others. To enable
      effective case-finding policies to be developed, an understanding of where
      people, and injecting drug users (IDUs) in particular, are accessing HCV antibody
      testing is needed. HCV antibody testing data were collected electronically from
      21 sentinel laboratories in England between 2002 and 2006 in this cross-sectional
      study. Service types of the physician requesting the HCV test were identified and
      classified. Differences in people being tested in each service type and over time
      were investigated. Over half a million people were tested in 5 years. Whilst most
      testing took place in hospital, a large proportion of people were tested in
      community care, particularly in general practice surgeries and genito-urinary
      medicine clinics. Younger people were more likely to be tested in community care,
      and there was evidence that testing differed according to ethnic status. IDUs
      were tested in all parts of the health services, although the highest proportion
      positive were from prisons and specialist services for drug users. Testing
      increased between 2002 and 2005 whilst the proportion of people testing positive
      declined. Routine laboratory data can provide valuable information on where
      people are being tested for HCV. Risk exposures should be investigated and
      testing targeted to people at higher risk for infection. Local laboratories
      should review data on testing locations and proportion positive to inform local
      initiatives to improve testing and yield.

PMID- 18637079
TI  - CD43 controls the intracellular growth of Mycobacterium tuberculosis through the
      induction of TNF-alpha-mediated apoptosis.
AB  - Establishment of Tuberculosis infection begins with the successful entry and
      survival of the pathogen within macrophages. We previously showed that macrophage
      CD43 is required for optimal uptake and growth inhibition of Mycobacterium
      tuberculosis both in vitro and in vivo. Here, we explore the mechanisms by which
      CD43 restricts mycobacterial growth in murine macrophages. We found that although
      M. tuberculosis grows more readily in resting CD43-/- macrophages, priming of
      cells with IFN-gamma returns the bacterial growth rate to that seen in CD43+/+
      cells. To discern the mechanisms by which M. tuberculosis exhibits enhanced
      growth within resting CD43-/- macrophages, we assessed the induction of
      inflammatory mediators in response to infection. We found that absence of CD43
      resulted in reduced production of TNF-alpha, IL-12 and IL-6 by M. tuberculosis
      infected macrophages. We also found that infected resting, but not activated CD43
      /- macrophages, showed decreased apoptosis and increased necrosis. Exogenous
      addition of the pro-inflammatory cytokine TNF-alpha restored control of M.
      tuberculosis growth and induction of apoptosis to CD43+/+ levels. We propose that
      CD43 is involved in the inflammatory response to M. tuberculosis and, through the
      induction of pro-inflammatory mediators, can regulate apoptosis to control
      intracellular growth of the bacterium.

PMID- 18637080
TI  - A double-blind randomized clinical trial evaluating the analgesic efficacy of
      ketorolac versus butorphanol for patients with suspected biliary colic in the
      emergency department.
AB  - OBJECTIVES: Patients presenting to the emergency department (ED) with suspected
      biliary colic often require intravenous (IV) analgesia. The choice of IV
      analgesia typically includes opioids and ketorolac. Although ultrasound (US) is
      the initial diagnostic study in these patients, nondiagnostic scans and a high
      clinical suspicion may require the patient to undergo hepatobiliary scintigraphy
      (HIDA). Opioids such as morphine interfere with the HIDA scan and thus may limit
      its value as an analgesic in the ED for these patients. Analgesics that do not
      interfere with HIDA scanning include ketorolac and butorphanol, an opioid agonist
      antagonist. This study evaluates the efficacy of IV ketorolac compared to
      butorphanol for the treatment of biliary colic pain in the ED. METHODS: Between
      June 2005 and February 2007, a convenience sample of patients presenting to the
      ED with abdominal pain suspected to be biliary colic were randomized to receive
      either 30 mg of IV ketorolac or 1 mg of IV butorphanol. Pain level was assessed
      using a 1 to 10 "faces" visual analog pain scale initially, as well as 15 and 30
      minutes after medication infusion. Side effect profiles and the need for rescue
      analgesia were also assessed. Patients and clinicians were blinded to the study
      drug given. RESULTS: Forty-six patients were enrolled in the study. Both groups
      had similar demographics and baseline pain scores. The mean (+/-standard
      deviation [SD]) pain score in the butorphanol group decreased from 7.1 (+/-1.7)
      to 2.1 (+/-2.2) after 30 minutes. The mean (+/-SD) pain score in the ketorolac
      group decreased from 7.4 (+/-2.0) to 3.1 (+/-3.3) after 30 minutes. Both groups
      had similar needs for rescue analgesia. Side effects included dizziness and
      sedation with butorphanol and nausea with ketorolac. CONCLUSIONS: Although
      limited by small sample size and convenience sample, this study demonstrates that
      both ketorolac and butorphanol provide pain relief in biliary colic. Both agents
      should be considered reasonable options in the ED treatment of biliary colic,
      especially in patients that may undergo HIDA.

PMID- 18637081
TI  - Triage presenting complaint descriptions bias emergency department waiting times.
AB  - OBJECTIVES: The authors aimed to determine whether certain emergency department
      (ED) triage "presenting complaint" descriptions are associated with shorter or
      longer waiting times, when compared with matched controls. METHODS: This was a
      retrospective, analytical study in three tertiary referral EDs. Data relating to
      adult patients with Australasian National Triage Scale (NTS) Category 3-5
      complaints, who presented over 1 year, were accessed. A pilot study of 25
      emergency physicians (EPs) identified five most liked and five most disliked
      presenting complaints. For each liked or disliked complaint, "cases" were
      identified using key words and phrases in the triage presentation description.
      For each case, the previous presentation at that institution with the same NTS
      category was used as a "control." Cases and controls were compared for waiting
      time and proportions seen within the Australasian College for Emergency Medicine
      (ACEM)-recommended waiting times. RESULTS: Data on 28,566 case-control pairs were
      examined. Compared to their controls, three of the five most liked complaints
      (dislocations, fractures, and palpitations) had significantly shorter waiting
      times, and significantly more were seen within the recommended waiting times (p <
      0.05). In contrast, three of the five most disliked complaints (dizziness,
      constipation, and back pain) had significantly longer waiting times, and
      significantly fewer were seen within the recommended waiting times (p < 0.05).
      Other presenting complaints showed similar, although nonsignificant, trends.
      CONCLUSIONS: Waiting times for patients with certain presenting complaints are
      significantly associated with triage presenting complaint descriptions. It is
      likely that these descriptions allow EPs to selectively seek or avoid patients
      with liked or disliked complaints, respectively. The impact of this for patients
      and ED flow needs investigation.

PMID- 18637082
TI  - Relapse after emergency department discharge for acute asthma.
AB  - OBJECTIVES: The objectives were to determine patient and treatment-response
      factors associated with relapse after emergency department (ED) treatment for
      acute asthma. METHODS: Subjects aged 18-55 years who were treated for acute
      asthma in 20 Canadian EDs prospectively underwent a structured ED interview and
      telephone contact 2 weeks later. RESULTS: Of 695 enrolled patients, 604 (86.9%)
      were discharged from the ED; follow-up was available in 529 (87.5%); 63% were
      female and the median age was 29 years. Most patients were discharged on oral
      (70.8%) and inhaled (60.1%) corticosteroids (CS); 2-week treatment adherences
      were 93.3 and 80.9%, respectively. Relapse occurred in 9.2% at 1 week (95%
      confidence interval [CI] = 7.1% to 12.0%) and 13.9% (95% CI = 11% to 17%) at 2
      weeks. In multivariable modeling, factors associated with relapse were ethnicity
      (risk ratio [RR] white = 0.66; 95% CI = 0.52 to 0.83); female gender (RR = 1.57;
      95% CI = 1.14 to 2.09); any ED visits in the past 2 years (RR = 1.47; 95% CI =
      1.18 to 1.80); ever admitted for asthma treatment (RR = 1.83; 95% CI = 1.09 to
      2.84); use of combined inhaled CS plus long-acting beta(2)-agonists (RR = 1.39;
      95% CI = 1.07 to 1.78) and of oral CS (RR = 1.35; 95% CI = 1.12 to 1.59) at the
      time of ED presentation. CONCLUSIONS: Ethnicity (white), female gender, prior ED
      visits and admissions for asthma, and recent treatments (especially oral CS) were
      associated with asthma relapse, which remains relatively common. Future research
      is required to target this high-risk group.

PMID- 18637083
TI  - Bedside detection of urine beta-hydroxybutyrate in diagnosing metabolic acidosis.
AB  - OBJECTIVES: While critically important, the rapid identification of the etiology
      of metabolic acidosis (MA) may be labor-intensive and time-consuming. Alcoholic,
      starvation, and severe diabetic ketoacidosis (AKA, SKA, and DKA, respectively)
      may produce beta-hydroxybutyrate (BOHB) in marked excess of acetone (ACET) and
      acetoacetate (AcAc). Unfortunately, current urine dipstick technology poorly
      detects ACET and cannot measure BOHB. The inability to detect BOHB might delay
      therapy for ketoacidoses or provoke unnecessary evaluation or empiric treatment
      of other causes of MA, such as toxic alcohol poisoning. The authors tested the
      previous assertion that commonly available hydrogen peroxide (H(2)O(2)) would
      improve BOHB detection. The effectiveness of alkalinization and use of a silver
      nitrate (AgNO(3)) catalyst was also assessed. METHODS: Control and urine test
      specimens containing from 0.5 to 800 mmol/L ACET, AcAc, and BOHB were prepared.
      Urine specimens were oxidized with H(2)O(2) (3%) 1:9 (H(2)O(2):urine),
      alkalinized with potassium hydroxide (KOH; 10%), exposed to AgNO(3) sticks, or
      altered with a combination of these methods in a random fashion. Three emergency
      physicians (EPs) blinded to the preparation technique evaluated urine dipsticks
      (Multistix, Bayer Corp.) placed in the specimens for "ketones." RESULTS:
      Multistix detected AcAc appropriately; ACET was detected only at high
      concentrations of >or=600 mmol/L. Multistix failed to measure BOHB at all
      concentrations tested. H(2)O(2) improved urinary BOHB detection, although not to
      clinically relevant levels (40 mmol/L). Alkalinization and AgNO(3) sticks did not
      improve BOHB detection beyond this threshold. CONCLUSIONS: Addition of H(2)O(2)
      (3%), alkalinization, or AgNO(3) sticks did not improve clinically meaningful
      urine BOHB detection. Clinicians should use direct methods to detect BOHB when
      suspected.

PMID- 18637084
TI  - Success of ultrasound-guided peripheral intravenous access with skin marking.
AB  - OBJECTIVES: The most effective technique for ultrasound-guided peripheral
      intravenous access (USGPIVA) is unknown. In the traditional short-axis technique
      (locate, align, puncture [LAP]), the target vessel is aligned in short axis with
      the center of the transducer. The needle is then directed toward the target under
      real-time ultrasound (US) guidance. Locate, align, mark, puncture (LAMP) requires
      the extra step of marking the skin at two points over the path of the vein and
      proceeding with direct visualization as in LAP. The difference in success between
      these two techniques was compared among variably experienced emergency physician
      and emergency nurse operators. METHODS: Subjects in an urban academic emergency
      department (ED) were randomized to obtain intravenous (IV) access using either
      LAP or LAMP after two failed blind attempts. Primary outcomes were success of the
      procedure and time to complete the procedure in variably experienced operators.
      RESULTS: A total of 101 patients were enrolled. There was no difference in
      success between LAP and LAMP, even among the least experienced operators. Of
      successful attempts, LAMP took longer than LAP (median 4 minutes, interquartile
      range [IQR] 4-10.5 vs. median 2.9 minutes, IQR 1.6-7; p = 0.004). Only the most
      experienced operators were associated with higher levels of success (first
      attempt odds ratio [OR] 6.64; 95% confidence interval [CI] = 2 to 22). Overall
      success with up to two attempts was 73%. Complications included a 2.8% arterial
      puncture rate and 12% infiltration rate. CONCLUSIONS: LAMP did not improve
      success of USGPIVA in variably experienced operators. Experience was associated
      with higher rates of success for USGPIVA.

PMID- 18637085
TI  - Emergent airway adjuncts: the tracheal tube introducer.

PMID- 18637086
TI  - Utilizing intraluminal pressure gradients to predict esophageal clearance: a
      validation study.
AB  - BACKGROUND: Esophageal bolus clearance requires a preferential esophagogastric
      pressure gradient sustained for a sufficient period. We aimed to validate a high
      resolution manometry (HRM) paradigm for predicting bolus clearance. METHODS:
      Twenty volunteers and 30 patients were studied with HRM during barium swallows
      with concurrent fluoroscopy. Simultaneous bolus domain pressure and
      esophagogastric junction (EGJ) obstruction pressure were plotted and flow
      permissive time was tallied during which the bolus domain pressure exceeded the
      EGJ obstruction pressure. Distal peristaltic integrity was assessed at
      incrementally increasing pressure isobaric contour thresholds from 15-40 mmHg.
      ROC analysis was performed to assess the sensitivity and specificity of cutoff
      values for flow permissive time and peristaltic amplitude for predicting
      incomplete clearance as verified fluoroscopically. RESULTS: Flow permissive time
      < or =2.5 s had a sensitivity of 86% and specificity of 92% for predicting
      incomplete clearance. In contrast, a 30-mmHg peristaltic amplitude had a
      sensitivity of only 48% and specificity of 88%. Incomplete clearance was variably
      attributable to functional EGJ obstruction, hiatus hernia, or impaired
      peristalsis. CONCLUSIONS: A detailed analysis of intraluminal pressure gradients
      in the distal esophagus and across the EGJ in the postdeglutitive period predicts
      esophageal bolus clearance with far greater accuracy than any threshold value of
      peristaltic amplitude.

PMID- 18637087
TI  - Lack of correlation between serum anti-HBcore detectability and hepatocellular
      carcinoma in patients with HCV-related cirrhosis.
AB  - BACKGROUND: While the likelihood of developing hepatocellular carcinoma (HCC) in
      patients coinfected with both HBV and HCV is increased, the role of previous
      exposure to HBV as a risk factor associated with tumor occurrence in subjects
      with HCV-related cirrhosis has not been fully investigated. AIM: To assess
      whether serum anti-HBc positivity, as a marker of previous HBV exposure, is
      associated with HCC development in HCV-related positive, hepatitis B surface
      antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon
      (IFN) monotherapy. PATIENTS AND: A database including 883 consecutive patients
      (557 men, mean age 54.7 yr) with histologically METHODS: proven cirrhosis treated
      with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled
      every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox
      multiple regression analysis. RESULTS: Mean follow-up was 96.1 months. Anti-HBc
      testing was available in 693 cases and, among them, 303 patients (43.7%) were
      anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0%vs
      58.7%, P= 0.03), had lower transaminase levels (3.3 +/- 2.0 vs 3.8 +/- 2.5
      u.l.n., P= 0.004), and had higher rate of alcohol intake (38.3%vs 22.5%, P <
      0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per
      100 person-years were 1.84 (95% CI 1.34-2.47) in the anti-HBc positive patients
      and 1.86 (95% CI 1.41-2.42) in anti-HBc negative ones. By Cox multiple
      regression, there was no association of serum anti-HBc with HCC development (HR
      1.03, 95% CI 0.69-1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76
      1.95). CONCLUSIONS: In comparison with anti-HBc negative subjects, serum anti-HBc
      positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN
      monotherapy did not show a greater risk of HCC.

PMID- 18637088
TI  - Biomarkers in gastrointestinal cancers.

PMID- 18637089
TI  - Predictors of patient-assessed illness severity in irritable bowel syndrome.
AB  - BACKGROUND: Conceptual models suggest that "irritable bowel syndrome (IBS)
      severity" is a multidimensional outcome that is related to, yet distinct from,
      health-related quality of life (HRQOL). Existing severity questionnaires are
      largely based on physician rather than patient-based ratings. Since severity is a
      patient-centered outcome, it is essential that future instruments are based on
      patients' self-perceptions of severity. We measured patient-derived predictors of
      severity in a large cohort of IBS patients. METHODS: We performed a cross
      sectional analysis in 755 IBS patients recruited at a university-based center.
      Subjects completed a bowel symptom questionnaire, SCL-90, and SF-36. The main
      outcome was patient-assessed "overall severity of gastrointestinal symptoms," as
      measured on a 0-20 scale (20 = most severe). We first developed a conceptual
      model of IBS, and then performed bivariate analyses to identify biopsychosocial
      predictors of severity. We then entered significant predictors into a
      multivariable model to measure the independent association of each predictor with
      severity. RESULTS: Six factors predicted severity: (a) abdominal pain rating (P <
      0.001); (b) belief that "something serious is wrong with body" (P < 0.001); (c)
      straining with defecation (P= 0.001); (d) myalgias (P= 0.02); (e) urgency with
      defecation (P= 0.03); and (f) bloating (P= 0.05). Severity correlated highly with
      HRQOL in bivariate, but not multivariate, analysis. CONCLUSION: Patient-derived
      severity in IBS is related to, yet distinct from, generic HRQOL. IBS severity is
      predicted by abdominal pain, bloating, straining, urgency, myalgias, and disease
      related concern. These symptoms fall along both poles of the "brain-gut axis,"
      indicating that a full assessment of patient severity must include a balanced
      biopsychosocial history.

PMID- 18637090
TI  - Reappraisal of the characteristics of glucose abnormalities in patients with
      chronic hepatitis C infection.
AB  - OBJECTIVES: There is growing evidence suggesting the mutual link between type 2
      diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the
      impact of HCV infection on the suite of glucose abnormalities has rarely been
      investigated. The study aimed to determine the difference regarding the
      prevalence and the characteristics of glucose abnormalities between chronic
      hepatitis C (CHC) patients and community-based controls. It also aimed to
      investigate the related clinical, virological, and histological features of
      glucose abnormalities in HCV infection. METHODS: Six hundred eighty-three CHC
      patients and 515 sex-/age-matched controls were included. Oral glucose tolerance
      test (OGTT) was performed in 522 CHC patients and 447 controls without known
      T2DM. Clinical data were assessed upon the different stages of glucose
      abnormalities based on OGTT results. RESULTS: The prevalence of normoglycemia,
      IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively.
      There was a significant linear trend from normoglycemia to T2DM in terms of age,
      family history of T2DM, and advanced liver fibrosis in CHC patients. For those
      CHC patients without fibrosis, the prevalence of glucose abnormalities reached
      67.9% high. All CHC patients carried a significantly higher prevalence than
      controls regarding those aged <65 yr. For those without known DM, there was a 3.5
      fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients
      in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70-4.56, P < 0.001).
      CONCLUSIONS: CHC patients carried a high prevalence of glucose abnormalities.
      Determination of glucose abnormalities by OGTT may be suggested.

PMID- 18637091
TI  - Efficacy of esomeprazole (20 mg once daily) for reducing the risk of
      gastroduodenal ulcers associated with continuous use of low-dose aspirin.
AB  - OBJECTIVES: Low-dose aspirin is standard treatment for prevention of
      cardiovascular events in at-risk patients. However, long-term administration of
      low-dose aspirin is associated with a greater risk of adverse events, including
      gastroduodenal ulcers. This study determined the efficacy of esomeprazole for
      reducing the risk of gastric and/or duodenal ulcers and dyspeptic symptoms in
      patients receiving continuous, low-dose aspirin therapy. METHODS: Patients aged >
      or =60 yr, without baseline gastroduodenal ulcer at endoscopy, who were receiving
      aspirin 75-325 mg once daily, were randomized to esomeprazole 20 mg once daily or
      placebo for 26 wk. The presence of endoscopic gastric and/or duodenal ulcers and
      esophageal lesions was assessed at weeks 8 and 26. Upper gastrointestinal
      symptoms were assessed at weeks 8, 16, and 26. RESULTS: The intention-to-treat
      population comprised 991 patients (esomeprazole, N = 493; placebo, N = 498).
      Twenty-seven patients (5.4%) in the placebo group developed a gastric or duodenal
      ulcer during 26 weeks' treatment compared with eight patients (1.6%) in the
      esomeprazole group (life-table estimates: 6.2%vs 1.8%; P= 0.0007). At 26 wk, the
      cumulative proportion of patients with erosive esophagitis was significantly
      lower for esomeprazole versus placebo (4.4% and 18.3%, respectively; P < 0.0001).
      At 26 wk, esomeprazole-treated patients were more likely to experience resolution
      of heartburn, acid regurgitation, and epigastric pain (P < 0.05). CONCLUSIONS:
      Esomeprazole 20 mg once daily reduces the risk of developing gastric and/or
      duodenal ulcers and symptoms associated with the continuous use of low-dose
      aspirin in patients aged > or =60 yr without preexisting gastroduodenal ulcers.

PMID- 18637092
TI  - Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells
      into patients with alcoholic liver cirrhosis.
AB  - OBJECTIVES: Recent advances in regenerative medicine, including hematopoietic
      stem cell (HSC) transplantation, have brought hope for patients with severe
      alcoholic liver cirrhosis (ALC). The aim of this study was to assess the safety
      and efficacy of administering autologous expanded mobilized adult progenitor
      CD34+ cells into the hepatic artery of ALC patients and the potential improvement
      in the liver function. METHODS: Nine patients with biopsy-proven ALC, who had
      abstained from alcohol for at least 6 months, were recruited into the study.
      Following granulocyte colony-stimulating factor (G-CSF) mobilization and
      leukapheresis, the autologous CD34+ cells were expanded in vitro and injected
      into the hepatic artery. All patients were monitored for side effects,
      toxicities, and changes in the clinical, hematological, and biochemical
      parameters. RESULTS: On average, a five-fold expansion in cell number was
      achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 x 10(8)
      pre infusion. All patients tolerated the procedure well, and there were no
      treatment-related side effects or toxicities observed. There were significant
      decreases in serum bilirubin (P < 0.05) 4, 8, and 12 wk post infusion. The levels
      of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement
      through the study period and were significant (P < 0.05) 1 wk post infusion. The
      Child-Pugh score improved in 7 out of 9 patients, while 5 patients had
      improvement in ascites on imaging. CONCLUSION: It is safe to mobilize, expand,
      and reinfuse autologous CD34+ cells in patients with ALC. The clinical and
      biochemical improvement in the study group is encouraging and warrants further
      clinical trials.

PMID- 18637093
TI  - 3-yr-follow-up of topical corticosteroid treatment for eosinophilic esophagitis
      in adults.
AB  - BACKGROUND: Eosinophilic esophagitis (EE) is a clinicopathologic syndrome
      comprising isolated eosinophilic inflammation of the esophagus, with symptoms of
      dysphagia, and possibly, reflux. It was initially described in children, and in
      recent years, there is a heightened awareness in adults. The etiology is not
      completely understood. The treatments include dietary manipulation, topical
      corticosteroids, systemic corticosteroids, Montelukast, and endoscopic dilation.
      In adults, there are no randomized trials demonstrating the efficacy of any
      particular treatment, and no prospective studies describing the natural history
      of the disease following treatment. METHODS: We performed an interval follow-up
      of patients treated with a swallowed corticosteroid inhaler. We contacted 51
      adult patients who were diagnosed with EE and treated with a swallowed
      corticosteroid inhaler between September 1, 1999, and May 31, 2003. All patients
      had received 6 wk of treatment with fluticasone 220 mEq/puff, four puffs
      swallowed twice daily for 6 wk. RESULTS: Thirty-two patients replied (63%) with a
      mean follow-up duration of 3.3 yr. Ninety-one percent of patients reported
      recurrent symptoms; a mean of 8.8 months after treatment was completed. Sixty
      nine percent of patients repeated treatment with the steroid inhaler at least
      once. CONCLUSIONS: It appears that EE is a chronic remitting disorder that
      requires more than one topical steroid treatment course.

PMID- 18637095
TI  - Natural course of chronic HCV and HBV infection and role of alcohol in the
      general population: the Dionysos Study.
AB  - BACKGROUND: Population-based studies of the natural course of chronic viral liver
      disease that consider comorbidity factors are lacking. Using data from the
      Dionysos Study, we quantified the burden of chronic viral liver disease and the
      role of alcohol intake to morbidity and mortality in a representative sample of
      subjects from the general population of two communities of Northern Italy.
      METHODS AND FINDINGS: We followed up 139 subjects with chronic hepatitis C virus
      (HCV) infection and 61 with chronic hepatitis B virus (HBV) infection for a
      median (IQR) time of 8.4 (1.0) and 8.3 (0.9) yr, respectively. Ethanol intake was
      evaluated using a food-frequency questionnaire, fatty liver (FL) was diagnosed by
      ultrasonography, and liver cirrhosis (LC) and hepatocarcinoma (HCC) were
      diagnosed by liver biopsy. Exact multivariable Poisson regression was performed
      to identify predictors of death. The incidence and remission rates of FL were 9.0
      and 29.7 in the HCV cohort and 4.0 and 30.4 per 1,000 person-years (PY) in the
      HBV cohort. Progression to LC and HCC was more common in the HCV than in the HBV
      cohort (4.5 vs 2.0 and 2.7 vs 2.0 per 1,000 PY, respectively). Ethanol intake was
      an independent predictor of LC in the HCV cohort [rate ratio (RR) = 4.15 (95% CI
      1.02-41.2) for every increase of 30 g/day of ethanol intake at baseline] and of
      death rate in both cohorts [RR = 8.53 (95% CI 1.40-24.61) and 3.56 (1.34 to
      26.50) for every increase of 30 g/day of ethanol intake at baseline].
      CONCLUSIONS: The morbidity and mortality rate of HBV and HCV infection in the
      general population is lower than that reported in secondary-care populations,
      blood donors, or clinical series. Ethanol intake is an independent predictor of
      LC in subjects with chronic HCV infection and an independent predictor of death
      in subjects with either HCV or HBV infection.

PMID- 18637097
TI  - Systematic review: persistence and severity in gastro-oesophageal reflux disease.
AB  - BACKGROUND: Management strategies for gastro-oesophageal reflux disease (GERD)
      are often inconsistent with the proposition that it is a persistent or chronic
      disease. AIM: To determine the persistence of reflux symptoms and complications
      associated with GERD. METHODS: Systematic searches of Medline and EMBASE.
      RESULTS: In longitudinal studies, 65% (95% CI 54-75%) of patients with
      complicated GERD and 70% (95% CI 57-83%) of patients with 'defined' GERD had
      persistent disease at follow-up, whereas 34% (95% CI 27-40%) with infrequent or
      mild reflux symptoms at baseline had persistent symptoms. Clinical trials of
      maintenance treatment for at least 6 months after healing of oesophagitis
      reported mean relapse rates of 75% (95% CI 68-82%) in patients taking placebo and
      28% (95% CI 21-35%) in those taking proton pump inhibitors. Retrospective studies
      reported that 34-41% of individuals with GERD recalled experiencing their
      symptoms for >10 years. The prevalence of GERD is high (10-20%), whereas the
      incidence is low (4.5-19.6 cases per 1000 person-years), suggesting that GERD is
      likely to persist for at least 18 years. CONCLUSIONS: Individuals with GERD have
      persistent reflux symptoms that merit management as a chronic disease; infrequent
      reflux symptoms are less likely to be chronic and may respond to different
      management strategies.

PMID- 18637096
TI  - Independent effects of cardiorespiratory fitness, vigorous physical activity, and
      body mass index on clinical gallbladder disease risk.
AB  - BACKGROUND AND AIMS: Incident self-reported physician-diagnosed clinical
      gallbladder disease was compared to BMI, body dimensions, physical activity
      (km/day run) and cardiorespiratory fitness (10 km race speed, meters per second
      [m/s]) in 29,110 male and 11,953 female runners. METHODS: Physician-diagnosed
      gallbladder disease was reported by 166 men (0.57%) and 112 women (0.94%) during
      (mean +/- SD) 7.74 +/- 1.84 and 7.42 +/- 2.10 years of follow-up, respectively.
      RESULTS: There was a progressive increase in age-adjusted risk with increasing
      BMI that accelerated sharply above 27.5 kg/m(2). Even among ostensibly healthy
      weight women, the age-adjusted risk was significantly greater above 22.5 kg/m(2)
      vis-a-vis the leanest women (P= 0.04). Age-adjusted risk declined with increasing
      fitness in both sexes. Compared to the least fit men and women, men who ran
      faster than 4.75 m/s had 83% lower risk (75% lower when adjusted for km/day and
      BMI) and women who ran faster than 4 m/s had 93% lower risk (85% lower adjusted
      for km/day and BMI). The fittest men (> or =4.75 m/s) were at significantly less
      risk than men who ran <3.25 m/s (P < 0.003) and between 3.25 and 3.75 m/s (P=
      0.03), and the fittest women (> or =4 m/s) were at significantly less risk than
      those who ran <2.8 m/s (P < 0.0001), between 2.8 and 3.2 (P= 0.0004), 3.2 and 3.6
      (P= 0.002), and 3.6 and 4.0 m/s (P= 0.005). Adjustment for BMI accounted for more
      of the risk reduction associated with fitness in women than men. The risk for
      clinical gallbladder disease was also significantly related to usual running
      distance (men: P= 0.01; females: P= 0.008), which was attributable to the
      leanness of the longer-distance runners. CONCLUSION: Clinical gallbladder disease
      risk was (a) concordantly related to BMI, (b) inversely related to usual running
      distance, and (c) inversely related to cardiorespiratory fitness independent of
      physical activity levels.

PMID- 18637098
TI  - Antipsychotic drugs and short-term mortality after peptic ulcer perforation: a
      population-based cohort study.
AB  - BACKGROUND: Peptic ulcer perforation is a serious surgical emergency with a
      substantial short-term mortality, but the influence of antipsychotic drug use on
      the prognosis remains unknown. AIM: To examine the association between
      antipsychotic drug use and 30-day mortality following peptic ulcer perforation.
      METHODS: This cohort study comprised 2033 patients with a first-time
      hospitalization with peptic ulcer perforation, in Northern Denmark, between 1991
      and 2004. Data on preadmission use of antipsychotics and other medications,
      psychiatric disease, other comorbidities and mortality were obtained through
      population-based medical databases. We used Cox regression analyses to compute
      adjusted mortality rate ratios (MRRs). RESULTS: One hundred and sixteen (5.7%)
      patients with peptic ulcer perforation were current users of antipsychotic drugs
      at the time of hospital admission and 205 (10.1%) were former users. The overall
      30-day mortality was 27%. Among current users of antipsychotics 30-day mortality
      was 39%. The adjusted 30-day MRR for current users of antipsychotic drugs
      compared with non-users was 1.7 (95% CI: 1.2-2.3). Former use was not a predictor
      of mortality. The increase in mortality was equal in users of conventional and
      atypical antipsychotics. CONCLUSION: Use of antipsychotic drugs is associated
      with substantially increased mortality following peptic ulcer perforation.

PMID- 18637099
TI  - Staged or simultaneous resection of synchronous liver metastases from colorectal
      cancer--a systematic review.
AB  - OBJECTIVE: A systematic review of the literature was undertaken to estimate the
      differences in length of hospital stay, morbidity, mortality and long-term
      survival between staged and simultaneous resection of synchronous liver
      metastases from colorectal cancer to determine the level of evidence for
      recommendations of a treatment strategy. METHOD: A Pub-med search was undertaken
      for studies comparing patients with synchronous liver metastases, who either had
      a combined or staged resection of metastases. Twenty-six were considered and 16
      were included based on Newcastle Ottawa Quality Assessment Scale. All studies
      were retrospective and had a general bias, because the staged procedure was
      significantly more often undertaken in patients with left-sided primary tumours
      and larger, more numerous and bi-lobar metastases. Analyses of primary outcomes
      were performed using the random effects model. RESULTS: For the reason of the
      heterogeneity of the observational studies, no odds ratios were calculated. In 11
      studies, there was a tendency towards a shorter hospital stay in the synchronous
      resection group. Fourteen studies compared total perioperative morbidity and
      lower morbidity was observed in favour of a combined resection. Fifteen studies
      compared perioperative mortality, which seemed to be lower with the staged
      approach. Eleven studies compared 5-year survival, which seemed to be similar in
      the two groups. CONCLUSION: No randomized controlled trials were identified, and
      hence a meta-analysis was not performed. The evidence level is II to III with
      grade C recommendations. Synchronous resections can be undertaken in selected
      patients, provided that surgeons specialized in colorectal and hepatobiliary
      surgery are available.

PMID- 18637100
TI  - Are topical oestrogens useful in faecal incontinence? Double-blind randomized
      trial.
AB  - BACKGROUND: Histopathological studies have shown the presence of oestrogenic
      receptors in the anal sphincter, which presumes a role in muscular trophism for
      circulating oestrogens. This could explain the increase in faecal incontinence
      (FI) in postmenopausal women. OBJECTIVE: To evaluate the effect of topical
      oestrogens (TE) in controlling symptoms of FI in postmenopausal women. Hypothesis
      The application of TE in postmenopausal women with FI improves continence.
      METHOD: We performed a prospective double-blind randomized trial applying TE to
      the anal mucosa in postmenopausal women with FI. STUDY PERIOD: 2005-2006. The
      patients were randomized into two groups: I--topical estriol, II--placebo. In
      both groups, the ointment was applied three times daily for a period of 6 weeks.
      We compared Wexner's FI score and the FI quality of life scale, before commencing
      and after 6 weeks of application. RESULTS: In this period we evaluated 36
      patients. Average age: 67 years (48-84). Group I: 18 patients and group II: 18
      patients, one patient was excluded. Wexner's FI score in group I was 11 (5-18)
      and 7 (0-19) with pre- and postapplication respectively (P = 0.002). Wexner's FI
      score in group II was 12 and 9 with pre- and postapplication respectively (P =
      0.013). When we compared the results between both groups, this was not
      statistically significant (P = 0.521). CONCLUSION: There is improvement of
      continence in both groups that had the ointment applied; nonetheless this study
      could not show that TE improves FI more than a placebo does.

PMID- 18637101
TI  - Influx of recent thymic emigrants into autoimmune thyroid disease glands in
      humans.
AB  - Autoimmune thyroid diseases (AITD) are considered as prototypic organ-specific
      autoimmune diseases, yet their underlying aetiology remains poorly understood.
      Among the various pathophysiological mechanisms considered, a failure of central
      tolerance has received little attention. Here we present evidence in favour of
      dysregulated thymic function playing a role in AITD. Flow-cytometric analyses
      conducted in peripheral blood lymphocytes from 58 AITD patients and 48 age- and
      sex-matched controls showed that AITD patients have significantly higher blood
      levels of CD4(+)CD45RA(+), CD4(+)CD31(+) and CD4/CD8 double-positive T
      lymphocytes, all markers of recent thymic emigrants (RTE). In addition, the alpha
      signal joint T cell receptor excision circles (TRECs) content (a molecular marker
      of RTEs) was higher in the group of AITD patients older than 35 years than in age
      matched controls. This was independent from peripheral T cell expansion as
      assessed by relative telomere length. Comparisons of TREC levels in peripheral
      blood lymphocytes and intrathyroidal lymphocytes in paired samples showed higher
      levels within the thyroid during the initial 30 months of the disease, indicating
      an influx of RTE into the thyroid during the initial stages of AITD.
      Additionally, a lack of correlation between TREC levels and forkhead box P3
      expression suggests that the intrathyroidal RTE are not natural regulatory T
      cells. These results uncover a hitherto unknown correlation between altered
      thymic T cell export, the composition of intrathyroidal T cells and autoimmune
      pathology.

PMID- 18637102
TI  - T cell cytokine polarity as a determinant of immunoglobulin A (IgA) glycosylation
      and the severity of experimental IgA nephropathy.
AB  - Immunoglobulin A (IgA) glycosylation, recognized as an important pathogenic
      factor in IgA nephropathy (IgAN), is apparently controlled by the polarity of T
      helper (Th) cytokine responses. To examine the role of cytokine polarity in IgAN,
      inbred mice were immunized by intraperitoneal priming with inactivated Sendai
      virus (SeV) emulsified in either complete Freund's adjuvant (CFA) or incomplete
      Freund's adjuvant (IFA), which promote Th1- or Th2-immune response, respectively,
      and then boosted identically twice orally with aqueous suspensions of inactivated
      virus. Next, some mice were challenged intranasally with infectious SeV. Mice
      primed with CFA or IFA had equal reductions in nasal viral titre relative to non
      immune controls, and equally increased serum levels of SeV-specific IgA antibody.
      Mice primed with CFA showed higher SeV-specific IgG than those with IFA.
      Splenocytes from mice primed with IFA produced copious amounts of interleukin
      (IL)-4 and IL-5, but little interferon-gamma and IL-2; those primed with CFA had
      reciprocal cytokine recall responses. Total serum IgA and especially SeV-specific
      IgA from mice primed with IFA showed a selective defect in sialylation and
      galactosylation. Although the frequency and intensity of glomerular deposits and
      haematuria did not differ, glomerulonephritis in mice primed with IFA and
      challenged with infectious virus was more severe than in those given CFA, as
      judged by serum creatinine level. We conclude that the polarity of T cell
      cytokines controls the pattern of IgA glycosylation and exerts direct or indirect
      effects on functional glomerular responses to immune complex deposition.

PMID- 18637103
TI  - Anti-calreticulin immunoglobulin A (IgA) antibodies in refractory coeliac
      disease.
AB  - Refractory coeliac disease (RCD) is a very rare and dangerous form of CD, in
      which gluten-free diet loses its therapeutic effect and the damage of intestinal
      mucosa persists. Because of the adherence to the diet, serological markers of CD
      [immunoglobulin A (IgA) antibodies against gliadin, tissue transglutaminase (tTG)
      and endomysium] are often missing in RCD patients. We found substantially
      elevated levels of IgA anti-calreticulin (CRT) antibodies in the sera of almost
      all RCD patients tested. These sera were negative for IgA antibodies to gliadin
      and tTG and only some of them showed IgA antibodies to enterocytes. Analysis of
      patients' IgA reactivity to CRT fragments (quarters and halves) by Western
      blotting revealed differences in the specificity of IgA antibodies between RCD
      and CD patients. We therefore used the Pepscan technique with synthetic
      overlapping decapeptides of CRT to characterize antigenic epitopes recognized by
      serum IgA antibodies of RCD patients. Employing this method we demonstrated
      several dominant antigenic epitopes recognized by IgA antibodies of RCD patients
      on the CRT molecule. Epitope GVTKAAEKQMKD was recognized predominantly by serum
      IgA of RCD patients. Our results suggest that testing for serum IgA antibodies
      against CRT and its selected peptide could be a very useful tool in RCD
      differential diagnosis.

PMID- 18637105
TI  - Inhibitors of vascular endothelial growth factor (VEGF) in the management of
      neovascular age-related macular degeneration: a review of current practice.
AB  - We review the fundamental changes that are now occurring to the management of
      neovascular (wet) age-related macular degeneration (AMD). An improved
      understanding of the role of vascular endothelial growth factor (VEGF) in the
      genesis of choroidal neovascular membranes has led to the creation and use of
      intravitreous anti-VEGF antibodies (bevacizumab and ranubizumab) and an aptamer
      (pegaptanib) in the treatment of these lesions. These new intravitreous
      injections for AMD have supplanted previous treatments in both efficacy and
      safety and are now the standard of care for neovascular AMD. We discuss the
      biochemistry of the anti-VEGF pathway. While there is substantial evidence for
      the use of ranubizumab and pegaptanib, the intravitreous administration of
      bevacizumab has not been tested in randomised controlled clinical trials. We
      review the evidence base for all three agents and the patho-physiological basis
      for adverse reactions to intravitreous VEGF blockade.

PMID- 18637104
TI  - Mannose-binding lectin gene polymorphic variants predispose to the development of
      bronchopulmonary complications but have no influence on other clinical and
      laboratory symptoms or signs of common variable immunodeficiency.
AB  - Mannose-binding lectin (MBL), activating protein of the lectin pathway of the
      complement system, is an important component of the non-specific immune response.
      MBL2 gene polymorphisms, both in the coding and promoter regions, lead to low or
      deficient serum MBL levels. Low serum MBL levels were shown to be associated with
      serious infectious complications, mainly in patients in whom other non-specific
      immune system barriers were disturbed (granulocytopenia, cystic fibrosis). We
      have analysed two promoter (-550 and -221) and three exon (codons 52, 54 and 57)
      MBL2 polymorphisms in a total of 94 patients with common variable
      immunodeficiency (CVID) from two immunodeficiency centres. Low-producing
      genotypes were associated with the presence of bronchiectasis (P = 0.009), lung
      fibrosis (P = 0.037) and also with respiratory insufficiency (P = 0.029). We
      could not demonstrate any association of MBL deficiency with age at onset of
      clinical symptoms, age at diagnosis, the number of pneumonias before diagnosis or
      serum immunoglobulin (Ig)G, IgA and IgM levels before initiation of Ig treatment.
      No association with emphysema development was observed, such as with lung
      function test abnormalities. No effect of MBL2 genotypes on the presence of
      diarrhoea, granuloma formation, lymphadenopathy, splenomegaly, frequency of
      respiratory tract infection or the number of antibiotic courses of the patients
      was observed. Our study suggests that low MBL-producing genotypes predispose to
      bronchiectasis formation, and also fibrosis and respiratory insufficiency
      development, but have no effect on other complications in CVID patients.

PMID- 18637106
TI  - Effects of gaze strategy on standing postural stability in older multifocal
      wearers.
AB  - BACKGROUND: Postural instability in older people is associated with an increased
      risk of falling. This experiment investigated the effects of different gaze
      strategies on postural stability in older people, when using distance single
      vision compared with multifocal (progressive addition lens and bifocal)
      spectacles. METHODS: Eighteen healthy older habitual multifocal spectacle-wearers
      (mean age 72.1 +/- 4.0 years) participated in a randomised, cross-over study.
      Postural stability during quiet standing was assessed as the root mean square
      excursion in the centre of pressure (RMS-COP) in the antero-posterior direction.
      Ground reaction force data were collected (for 30 seconds), while subjects viewed
      one of two visual targets (one square metre) of different spatial frequencies and
      contrasts, while wearing either distance single-vision or multifocal (progressive
      addition and bifocal) spectacles. The visual targets were positioned either ahead
      at eye-level or on the ground (viewing distance 2.06 metres) and viewed under the
      following head-gaze conditions; 'head neutral-gaze forward', 'head flexed-gaze
      down' and 'head neutral-gaze down'. RESULTS: The type of spectacles worn or the
      target viewed had no significant effect on postural stability but postural
      stability deteriorated (antero-posterior RMS-COP excursion increased) in the
      'head neutral-gaze down' compared with the 'head flexed-gaze down' and 'head
      neutral-gaze forward' conditions (5.9, 5.5 and 5.0 mm respectively, p < 0.001).
      CONCLUSIONS: Multifocal use had no effect on standing postural stability.
      Irrespective of spectacles worn, when fixating a visual target positioned at
      ground level, postural stability was better in the 'head flexed-gaze down'
      condition compared with the 'head neutral-gaze down' condition. A useful strategy
      to reduce falling in the older person might be to advise multifocal and distance
      single-vision spectacle-wearers to flex their heads rather than just lower their
      eyes when looking downwards.

PMID- 18637107
TI  - Effect of corneal thickness on intraocular pressure measurements with the Pascal
      dynamic contour, Canon TX-10 non-contact and Goldmann applanation tonometers in
      healthy subjects.
AB  - PURPOSE: To investigate the effects of central corneal thickness (CCT) on
      intraocular pressure (IOP) measurements of the Pascal dynamic contour tonometry
      (DCT), Canon TX-10 non-contact tonometry (NCT) and Goldmann applanation tonometry
      measurements (GAT) in healthy subjects. METHODS: IOP values of 135 eyes with
      normal corneas of 135 healthy volunteers were determined by DCT, NCT and by GAT.
      The CCT was measured using an ultrasonic pachymeter after all IOP determinations
      had been made. RESULTS: When DCT measurements were compared (IOP = 17.52 +/- 2.0
      mmHg) with NCT measurements (IOP = 16.54 +/- 2.77 mmHg) and GAT measurements (IOP
      = 15.07 +/- 2.35 mmHg), DCT measurements were significantly higher than NCT and
      GAT (p < 0.001). There was a significant correlation between CCT with both NCT (r
      = 0.260, p = 0.003) and GAT measurements (r = 0.257, p = 0.005). There was a weak
      correlation that was not statistically significant between CCT and DCT (r =
      0.160, p = 0.079). CONCLUSION: The IOP measurements with DCT seem to be less
      dependent on CCT. NCT appears to be more affected by variation in CCT than GAT.

PMID- 18637108
TI  - Fixation stability during Rarebit Fovea Test.
AB  - BACKGROUND: Unstable fixation has been reported to be a common cause of
      unreliable results in perimetry. The Rarebit Fovea Test (RFT) is a computerised
      foveal function test that evaluates the 4 x 3 degrees central visual field, using
      very small test stimuli. To minimise the test time, no fixation control is used.
      Instead, stable fixation is facilitated by the use of a dynamic fixation target.
      The aim of the current study was to evaluate fixation stability during a RFT
      examination by continuous recording of the eye movements. METHOD: Twelve healthy
      subjects were enrolled in the study together with two amblyopic subjects. A three
      dimensional eye tracker was used to measure eye movements during two test
      sessions. All subjects went through one session of fixation measurement with
      stimulus presentation and one session without stimulus presentation. Both
      sessions lasted approximately 90 seconds. RESULTS: Mean hit rate (MHR) in the
      whole group was 89.7 per cent. Five out of 14 subjects had abnormal RFT results.
      There was no significant difference in fixation stability either between the test
      sessions with and without stimulus presentations (p = 0.79) or between the
      subjects with abnormal (n = 5) and normal (n = 11) MHR, (p = 0.55). CONCLUSION:
      Fixation seems stable during RFT testing, thus the test design and fixation
      target used in the RFT could be considered adequate, at least in subjects with
      normal or near normal visual function. Further studies are needed to evaluate how
      different visual abnormalities will affect fixation stability during RFT testing.

PMID- 18637109
TI  - Monocular nystagmus with sectoral optic nerve hypoplasia in a patient with septo
      optic dysplasia.
AB  - This case depicts an unusual presentation of septo-optic dysplasia. A four-year
      old female presented with monocular nystagmus and temporal optic disc pallor in
      her left eye. Despite a normal sized optic nerve head, magnetic resonance imaging
      (MRI) showed a hypoplastic intraorbital and intracranial left optic nerve in the
      absence of a septum pellucidum. She was subsequently diagnosed with septo-optic
      dysplasia with sectoral optic nerve head hypoplasia.

PMID- 18637110
TI  - Orienteers with poor colour vision require more than cunning running.
AB  - BACKGROUND: Highly detailed colour coded maps are used in the sport of
      orienteering to enable competitors to navigate from one check point to another
      and to provide guidance on the nature of the terrain to be traversed. The colours
      are defined by the International Orienteering Foundation (IOF) and are said to
      have been chosen so they will not be confused by competitors who have abnormal
      colour vision. However, there are anecdotal reports that individuals with colour
      vision defects do have problems with the colour coding. METHOD: A Minolta
      Spectrophotometer CM-503i was used to measure the CIE x,y chromaticity co
      ordinates and the reflectances of the standard colours recommended by the IOF for
      the colour coding of orienteering maps, as well as the colours on two maps used
      in orienteering events. RESULTS: Four pairs of IOF standard colours are likely to
      be confused by protan observers and four pairs by deutan observers. There were
      three pairs of colours likely to be confused by both deutan and protan observers
      on one of the competition maps and one pair likely to be confused by protan
      observers on the other map. Some of the colours on the actual competition maps
      differed noticeably from the standard IOF colours. DISCUSSION: Orienteers with
      more severe forms of abnormal colour vision are likely to be disadvantaged by
      their inability to differentiate some colours used on orienteering maps. The IOF
      should choose different colours that are less likely to be confused or should
      employ a redundant code (such as a pattern or texture). There is need for better
      quality control of the colours of competition maps to ensure they do conform to
      the IOF standard colours.

PMID- 18637111
TI  - Thyroid disease induced diplopia.
AB  - This report describes a patient who was suffering from incomitant vertical
      diplopia due to Graves' ophthalmopathy. Previous optical treatment was a
      diffusing lens for the left eye resulting in monocular vision only. We proceeded
      to measure the amount of diplopia and prescribed a vertical Fresnel prism to be
      placed on the left spectacle lens to alleviate his diplopia and resolve his
      mobility problems. The amount of prism was further reduced by five prism dioptres
      after extraocular muscle surgery.

PMID- 18637112
TI  - The use of complementary therapy by men with prostate cancer in the UK.
AB  - The study aims were to determine the use of complementary therapies (CT) by men
      with prostate cancer, and to explore factors influencing CT use and attitudes
      toward CT use. A cross-sectional survey design was used in which a postal
      questionnaire was mailed to an eligible sample of 405 patients with prostate
      cancer receiving outpatient treatment in a London teaching hospital. The primary
      outcomes were the prevalence of CT use and the relationship between CT use and
      mental health status. Two hundred and ninety-four patients (73%) responded, of
      whom 25% were using CT. The most frequently used CTs were vitamins, low-fat
      diets, lycopene and green tea. Multivariate analyses revealed no differences in
      mental health scores between CT users and non-users. CT users were younger (OR
      0.93, 95% CI 0.89-0.97) and were more likely to be receiving conservative
      management in the form of 'active surveillance' (OR 5.23, 95% CI 1.78-15.41)
      compared with non-users. Over half of the participants (55%) wanted to learn more
      about CT. Forty-three per cent of CT users had not informed any doctor about
      their CT use. Clinicians need to be aware of the prevalence of CT use amongst
      patients with prostate cancer, considering the potential harm that could be
      caused by interactions with conventional treatments.

PMID- 18637113
TI  - A retrospective audit exploring the use of relaxation as an intervention in
      oncology and palliative care.
AB  - The benefits of relaxation in cancer care have been well documented within the
      literature, with the majority of research being undertaken by nursing
      professionals. However, evidence of the effectiveness of relaxation interventions
      by occupational therapists is lacking. Occupational therapists are in an ideal
      situation to provide information and practical relaxation sessions. Although in
      numerical terms, the outcome of relaxation interventions is small, functional
      outcome related to quality of life and independence in activities of daily living
      is immeasurable. This article reports the findings of a retrospective audit
      exploring relaxation-specific referrals to occupational therapy, and identifies
      effectiveness of a variety of different techniques currently employed within this
      specific programme. Patients with a primary diagnosis of breast cancer were the
      most frequently seen, and this prevalence is reflected in current national
      statistics. Similarly, those between 50 and 59 years of age comprised the largest
      group. Guided visualization was the most commonly used technique, although there
      appeared to be very little change in perceived tension between all the
      techniques. Further study of the impact relaxation has on occupational
      performance would be worthwhile.

PMID- 18637114
TI  - Effects of complex decongestive physiotherapy on the oedema and the quality of
      life of lower unilateral lymphoedema following treatment for gynecological
      cancer.
AB  - There is increasing interest in the health-related quality of life (QOL) of
      patients with chronic lymphoedema. The purpose of the present study was to
      ascertain whether or not complex decongestive physiotherapy (CDP) for 57
      gynecological cancer patients with unilateral lymphedema results in a measurable
      change in the oedema and QOL, and % excess volume correlated with change in QOL.
      % excess volume was significantly (P<0.05) decreased after CDP. The QOL scores
      were significantly (P<0.05) higher than the scores at baseline, indicating an
      improvement in the QOL. The change in % excess volume was associated with a
      change in physical functioning, social functioning, role-physical, bodily pain
      and general health at baseline and 1 month (P<0.05). This study suggests that
      significant improvements are made in the QOL of gynecological cancer patients
      with unilateral lymphoedema after CDP, which is necessarily correlated with limb
      reduction.

PMID- 18637115
TI  - Serum levels of tumour necrosis factor-alpha and interleukin-6 and their
      correlation with body mass index, weight loss, appetite and survival rate-
      preliminary data of Viennese outpatients with metastatic cancer during palliative
      chemotherapy.
AB  - The serum cytokine levels (in particular interleukine-6 (IL-6) and tumour
      necrosis factor-alpha (TNF-alpha)) of 61 advanced stage cancer patients receiving
      palliative chemotherapy as outpatients were determined with quantikine
      immunoassays. The values were correlated with body mass index (BMI), weight loss
      and appetite. Furthermore cytokine levels of patients who have died within one
      year were compared with those of patients who have survived more than a year.
      Serum levels of IL-6 (median: 1.93 pg/ml, range: 0.32-42.87) and of TNF-alpha
      (median: 2.55 pg/ml, range: 1.03-34.06) did not correlate with BMI, weight loss
      and appetite. Serum IL-6 levels of patients with survival time less than one year
      were significantly higher than the levels of patients who survived more than one
      year, no significant differences in TNF-alpha serum levels were evident. The data
      of this observation are consistent with current literature. Due to changes in
      serum levels of proinflammatory cytokines in response to chemotherapy and
      additional therapy, it is unlikely that IL-6 and TNF-alpha can be used as
      independent indicators for weight loss and appetite. Nevertheless, high serum
      levels of IL-6 correlate with short-time mortality.

PMID- 18637116
TI  - Understanding the concept of chemotherapy-related nausea: the patient experience.
AB  - The aim of this study was to explore the experience of chemotherapy-related
      nausea in patients with cancer. A qualitative study was carried out with 17
      patients who had experienced nausea during their chemotherapy in the UK and USA.
      Nausea was described as distressing and complex symptom. Patients attempted to
      construct an understanding of nausea using cognitive processes such as analysing
      their experience of nausea and related symptoms, attributing causation to nausea
      and comparing their experiences not only to their own expectations, but also to
      others' symptom experiences. A number of concurrent and associated symptoms
      linked with nausea were identified. Preliminary evidence emerged for nausea as
      part of a cluster of symptoms. Anti-emetic medication, provider-directed
      management strategies and self-management strategies were used by patients to
      minimize the effects of nausea. Self-management techniques, such as dietary
      strategies, were rooted in participants' understanding of nausea and their
      beliefs about what caused nausea, and there was little evidence of guidance from
      professionals beyond advice about medication management. This study reveals some
      of the complexities behind chemotherapy-induced nausea, including a potential
      symptom cluster, and contributes towards a clearer understanding of this symptom
      and its effects on patients' lives.

PMID- 18637117
TI  - Truncated P-cadherin is produced in oral squamous cell carcinoma.
AB  - Cadherins belong to a family of homophilic cell-cell adhesion proteins that are
      responsible for the establishment of a precise cell architecture and tissue
      integrity. Moreover, experimental data suggest that loss of intercellular
      adhesion is inversely correlated with cellular differentiation. Furthermore,
      dedifferentiation is closely linked to tumor progression. Recently, we have shown
      that a secreted 50 kDa N-terminal fragment of P-cadherin plays a role in the
      progression of malignant melanoma. In this study, we have detected both the full
      length and the truncated versions of P-cadherin in cell lysates of differentiated
      head and neck oral squamous cell carcinoma cell lines, whereas in cell lysates of
      dedifferentiated cell lines, we detected only the truncated 50 kDa version of P
      cadherin. Treatment of the cell lines with a recombinantly expressed
      biotinylated, soluble 50 kDa form of the N-terminal part of P-cadherin revealed a
      major effect on cell aggregation and migration of oral squamous cell carcinoma
      cells. However, the 50 kDa N-terminal fragment of P-cadherin did not show any
      influence on cell proliferation in 2D and 3D cell culture. These results suggest
      that generation of truncated P-cadherin during the progression of oral squamous
      carcinoma attenuates tissue integrity, facilitates cellular separation, and leads
      to the acquisition of a more migratory phenotype.

PMID- 18637118
TI  - Hepatitis C virus internal ribosome entry site-mediated translation is stimulated
      by cis-acting RNA elements and trans-acting viral factors.
AB  - Translation initiation of hepatitis C virus (HCV) occurs through an internal
      ribosome entry site (IRES) located at its 5'-end. As a positive-stranded RNA
      virus, HCV uses its genome as a common template for translation and replication,
      but the coordination between these two processes remains poorly characterized.
      Moreover, although genetic evidence of RNA-protein interactions for viral
      replication is accumulating because of subgenomic replicons and a recent culture
      system for HCV, such interactions are still contentious in the regulation of
      translation. To gain insight into such mechanisms, we addressed the involvement
      of cis and trans viral factors in HCV IRES activity by using a cell-based RNA
      reporter system. We found that the HCV 3' noncoding region (NCR) strongly
      stimulates IRES efficiency in cis, depending on the genotype and the cell line.
      Moreover, we confirmed the role of the core protein in viral gene expression as
      previously reported in vitro. Surprisingly, we observed a similar effect, i.e. a
      twofold increase under low amounts of NS5B RNA polymerase, followed by a decrease
      at higher concentrations. However, no contribution of NS5A to HCV IRES-mediated
      translation was noted and no cooperative effect could be detected between 3' NCR
      and viral proteins or between proteins. Collectively, these results suggest that
      HCV RNA translation is regulated, and that the switch from translation to
      replication might involve a sequential requirement for both cis and trans viral
      factors, because of their apparent lack of synergy, probably with the aid of host
      factors.

PMID- 18637119
TI  - Protein kinase Cepsilon: the mitochondria-mediated signaling pathway.
AB  - Mitochondria, which are the cellular energy plants, also act as the integration
      center of cellular signaling pathways. Apoptosis is a well-known pathway in which
      mitochondria are involved. Protein kinase Cepsilon has been classified as a novel
      type of protein kinase C and is involved in many cellular events regulating
      mitochondrial function. Much evidence has accumulated regarding the relationships
      between mitochondria-mediated apoptosis and protein kinase Cepsilon. Therefore,
      by focusing on these relationships, in particular the anti-apoptotic effects of
      protein kinase Cepsilon on mitochondrial function, we highlight the importance
      and significance of protein kinase Cepsilon in cell survival and death.

PMID- 18637120
TI  - Protein kinase Cepsilon: multiple roles in the function of, and signaling
      mediated by, the cytoskeleton.
AB  - Recent studies have established essential roles of protein kinase Cepsilon in
      signaling pathways controlling various functions of microfilaments and
      intermediate filaments by modulating multiple cytoskeletal proteins. This review
      summarizes recent progress in our understanding of the roles of protein kinase
      Cepsilon in the functions and signaling of microfilaments and intermediate
      filaments, with a focus mainly on cell-matrix and cell-cell interactions,
      migrations and contraction, in addition to its relevance in the development of
      several diseases, such as malignant tumors or cardiac disease.

PMID- 18637121
TI  - Protein kinase Cepsilon: function in neurons.
AB  - Protein kinase Cepsilon is expressed at higher levels in the brain compared to
      other tissues such as the heart and kidney, suggesting that it plays an important
      role in the nervous system. Several neural functions of PKCepsilon, including
      neurotransmitter release and ion channel regulation, have been identified using
      PKCepsilon knockout mice. In this review, we focus on the involvement of protein
      kinase Cepsilon in neurite outgrowth, presynaptic regulation, alcohol actions,
      ischemic preconditioning and pain.

PMID- 18637122
TI  - Protein kinase Cepsilon: novel aspects of its multiple functions in cellular
      signaling.

PMID- 18637123
TI  - Multiple myeloma--an update on diagnosis and treatment.
AB  - Multiple myeloma is a plasma cell (PC) malignancy characterized by the
      accumulation of monoclonal PCs in the bone marrow and the production of large
      amounts of a monoclonal immunoglobulin or paraprotein. In the past years, new
      approaches in the diagnosis and treatment were introduced aiming to identify high
      risk patients who need proper anti-myeloma treatment. Intensive therapy including
      autologous hematopoietic stem cell transplantation and the new agents bortezomib,
      thalidomide, and lenalidomide have improved patients' responses. Further
      optimalization of the different treatment schedules in well-defined patient
      groups may prolong their survival. Patient stratification is currently based on
      patient characteristics, extent of myeloma disease, and associated cytogenetic
      and laboratory anomalies. More and more gene expression studies are introduced to
      stratify patients and to individualize therapy.

PMID- 18637124
TI  - Psychosocial QOL is an independent predictor of overall survival in newly
      diagnosed patients with multiple myeloma.
AB  - Only few studies have analyzed quality of life (QOL) and its association with
      prognosis in patients with multiple myeloma. We studied QOL at start of
      conventional treatment to evaluate the impact of symptomatic myeloma on QOL and
      to determine the prognostic significance of various dimensions of QOL. Our study
      provided further evidence of the significant impairment of QOL in patients with
      multiple myeloma at onset of therapy. Furthermore, our data showed a closer
      correlation between the more physical QOL scales such as pain, fatigue, physical
      functioning and global QOL with the activity of the disease than between
      psychosocial dimensions such as role, emotional, social, and cognitive
      functioning and the status of the disease. Multivariate analyses including each a
      QOL scale and known prognostic parameters (response to therapy, creatinine level,
      calcium, LDH, Hb, beta2-microglobulin, and albumin) revealed a marked difference
      in the prognostic significance between psychosocial and other QOL scales. All
      psychosocial dimensions of QOL were found to be independent prognostic factors,
      while physical QOL and global QOL were eliminated by disease-associated
      prognosticators. Taken together, QOL was found to be significantly impaired in
      myeloma patients at start of therapy. Psychosocial, but not physical dimensions
      of QOL were found to be independent prognostic factors.

PMID- 18637126
TI  - Characterization of the structural and molecular defects in fibres and follicles
      of the Merino felting lustre mutant.
AB  - The felting lustre (FL) mutation found in Merino sheep results in a fleece that
      has a lustrous appearance and readily felts. This phenotype was described 50
      years ago to result from the mutation of a single gene, but the molecular and
      cellular changes in the wool are not well understood. In this study, follicle and
      fibre material of FL mutant (n = 3) and normal control (n = 5) Merino ewes was
      compared using histological analysis, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), real-time polymerase chain reaction (qPCR) and
      electron microscopy [scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM)]. Histological examination suggested that follicle structure in
      FL mutants is essentially normal, while SDS-PAGE analysis found that some low
      molecular weight keratin-associated proteins (KAP) were present at much lower
      levels in FL wool. Examination of transcript prevalence revealed that the KAP6.1,
      KAP7 and KAP8 genes in FL mutant follicles are downregulated, while the KAP2.12
      and KAP4.2 genes are upregulated. TEM analysis indicated that there is only one
      type of cortical cell, the paracortical cell, in the fibre of FL mutants, while
      there are paracortical and orthocortical cells in fibres of normal Merino sheep.
      In contrast, SEM suggested the surface topography of FL wool fibres is normal.
      The evidence presented here strongly suggests that the properties of FL wool can
      be ascribed, at least in part, to the lower content of high glycine/tyrosine
      proteins and the reduction in orthocortical cells in mutant wool fibres.

PMID- 18637125
TI  - N1421K mutation in the glycoprotein Ib binding domain impairs ristocetin- and
      botrocetin-mediated binding of von Willebrand factor to platelets.
AB  - von Willebrand disease (VWD) is a common inheritable bleeding disorder caused by
      deficiency of von Willebrand Factor (VWF), which is involved in platelet adhesion
      and aggregation. We report a family consisting of three patients with VWD
      characterized by an apparently normal multimeric pattern, moderately decreased
      plasma factor VIII (FVIII) and VWF levels, and disproportionately low-plasma
      VWF:RCo levels. The patients were found to be heterozygous for the novel N1421K
      mutation, caused by a 4263C > G transversion in exon 28 of the VWF gene coding
      for the A1 domain. Botrocetin- and ristocetin-mediated binding of plasma VWF to
      GPIb were reduced in the patients. In vitro mutagenesis and expression in COS-7
      cells confirmed the impairment of the mutant in botrocetin- and ristocetin
      mediated VWF binding to GPIb. VWF collagen binding capacity was unaffected in
      plasma from the heterozygous individuals as well as in medium from transfected
      COS-7 cells. Our findings indicate that the N1421K substitution in the VWF
      affects the GPIb binding site or a recognition element by a conformational change
      of the A1 domain.

PMID- 18637127
TI  - Partial purification and characterization of RNase P from human peripheral
      lymphocytes.
AB  - Ribonuclease P (RNase P) is ubiquitous and essential Mg(2+)-dependent
      endoribonuclease that catalyzes the 5'-maturation of transfer RNAs. RNase P and
      the ribosome are so far the only ribozymes known to be conserved in all kingdoms
      of life. Eukaryotic RNase P activity has been detected in nuclei, mitochondria
      and chloroplasts and demonstrates great variability in sequence and subunit
      composition. In the last few years we have developed methodologies and pursued
      projects addressing the occurrence, distribution and the potential physiological
      role of RNase P in human epidermal keratinocytes. In view of the vital importance
      of lymphocytes for an effective immune system and their successful application
      after transfection with RNase P-associated external guide sequences in gene
      therapy, we concerned ourselves with the isolation and characterization of RNase
      P of peripheral human lymphocytes. We developed a method described herein, that
      will enable the study of the possible involvement of this ribozyme in the
      pathogenetic mechanisms of diverse autoimmune, inflammatory and neoplastic
      cutaneous disorders and may facilitate the further development of RNase P-based
      technology for gene therapy of infectious and neoplastic dermatoses.

PMID- 18637128
TI  - Protein kinase C isoenzymes differentially regulate the differentiation-dependent
      expression of adhesion molecules in human epidermal keratinocytes.
AB  - Epidermal expression of adhesion molecules such as desmogleins (Dsg) and
      cadherins is strongly affected by the differentiation status of keratinocytes. We
      have previously shown that certain protein kinase C (PKC) isoforms differentially
      alter the growth and differentiation of human epidermal HaCaT keratinocytes. In
      this paper, using recombinant overexpression and RNA interference, we define the
      specific roles of the different PKC isoenzymes in modulation of expression of
      adhesion molecules in HaCaT keratinocytes. The level of Dsg1, a marker of
      differentiating keratinocytes, was antagonistically regulated by two Ca
      independent 'novel' nPKC isoforms; i.e. it increased by the differentiation
      promoting nPKCdelta and decreased by the growth-promoting nPKCepsilon. The
      expression of Dsg3 (highly expressed in proliferating epidermal layers) was
      conversely regulated by these isoenzymes, and was also inhibited by the
      differentiation inducer Ca-dependent 'conventional' cPKCalpha. Finally, the
      expression of P-cadherin (a marker of proliferating keratinocytes) was regulated
      by all of the examined PKCs, also in an antagonistic manner (inhibited by
      cPKCalpha/nPKCdelta and stimulated by cPKCbeta/nPKCepsilon). Collectively, the
      presented results strongly argue for the marked, differential, and in some
      instances antagonistic roles of individual Ca-dependent and Ca-independent PKC
      isoforms in the regulation of expression of adhesion molecules of desmosomes and
      adherent junctions in human epidermal keratinocytes.

PMID- 18637129
TI  - Strict sun protection results in minimal skin changes in a patient with xeroderma
      pigmentosum and a novel c.2009delG mutation in XPD (ERCC2).
AB  - We examined the clinical, molecular and genetic features of a 16-year-old boy
      (XP2GO) with xeroderma pigmentosum (XP) and progressive neurological symptoms.
      The parents are not consanguineous. Increased sun sensitivity led to the
      diagnosis of XP at 2 years of age and a strict UV protection scheme was
      implemented. Besides recurrent conjunctivitis and bilateral pterygium, only mild
      freckling was present on his lips. He shows absent deep tendon reflexes,
      progressive sensorineural deafness and progressive mental retardation. MRI shows
      diffuse frontal cerebral atrophy and dilated ventricles. Symptoms of
      trichothiodystrophy (brittle hair with a tiger-tail banding pattern on polarized
      microscopy) or Cockayne syndrome (cachectic dwarfism, cataracts, pigmentary
      retinopathy and spasticity) were absent. XP2GO fibroblasts showed reduced post-UV
      cell survival (D(37) = 3.8 J/m(2)), reduced nucleotide excision repair, reduced
      expression of XPD mRNA and an undetectable level of XPD protein. Mutational
      analysis of the XPD gene in XP2GO revealed two different mutations: a common
      p.Arg683Trp amino acid change (c.2047C>T) known to be associated with XP and a
      novel frameshift mutation c.2009delG (p.Gly670Alafs*39). The latter mutation
      potentially behaves as a null allele. While not preventing neurological
      degeneration, early diagnosis and rigorous sun protection can result in minimal
      skin disease without cancer in XP patients.

PMID- 18637130
TI  - Role of protein kinase C delta in X-ray-induced apoptosis of keratinocyte.
AB  - In this study, we investigated the process of X-ray-induced apoptosis of skin
      keratinocyte, and the functional role of protein kinase C delta (PKCdelta) and
      downstream signalling cascade. High-dose X-ray irradiation (10 Gy) led to the
      apoptosis of HaCaT keratinocyte, accompanied by PKCdelta cleavage. Treatment with
      PKCdelta inhibitor and adenoviral transduction of dominant-negative PKCdelta
      clearly inhibited the X-ray-induced apoptosis of keratinocyte. In addition, X-ray
      induced the phosphorylation of extracellular signal-regulated kinases 1/2
      (ERK1/2) and inhibition by ERK1/2 inhibitor abrogated the X-ray-induced
      apoptosis. Interestingly, overexpression of dominant-negative PKCdelta markedly
      blocked the X-ray-induced phosphorylation of ERK1/2, suggesting that ERK1/2 is
      the functional downstream effector of PKCdelta. Next, we investigated the
      difference between UVB and X-ray response. UVB induced the apoptosis of
      keratinocyte in a PKCdelta-dependent manner, similar to X-ray response. However,
      UVB irradiation induced the phosphorylation of c-jun N-terminal kinases (JNK) and
      inhibition of JNK significantly protected the UVB-induced apoptosis. These
      results demonstrate that PKCdelta is a key regulator in X-ray-induced apoptosis
      of keratinocyte and suggest that there is subtle difference in downstream
      signalling cascade between UVB and X-ray response of keratinocyte.

PMID- 18637131
TI  - The contribution of melanocortin 1 receptor gene polymorphisms and the agouti
      signalling protein gene 8818A>G polymorphism to cutaneous melanoma and basal cell
      carcinoma in a Polish population.
AB  - In this study, we assessed the role of melanocortin-1 receptor (MC1R) and agouti
      signalling protein (ASIP) polymorphisms in cutaneous melanoma and basal cell
      carcinoma (BCC) development in a Polish population. We enrolled 108 patients with
      skin malignant melanoma (MM) and 102 patients with BCC. The control group
      consisted of 93 non-red haired patients, without history of skin cancers and 30
      healthy individuals with red hair colour (RHC) phenotype. The complete MC1R exon
      was sequenced and the A8818G polymorphism of the ASIP gene was analysed using the
      SnaPshot protocol. Selected MC1R mutations were additionally examined using a
      convenient minisequencing assay. The study confirmed the important role of MC1R R
      variants in determining physiological variation in hair and skin colour. Our data
      show that individuals with R mutations had a 3.7-fold increase in melanoma risk
      and a 3.3-fold increase in BCC risk. Especially, variant R151C significantly
      increased the risk of both MM and BCC. The studied ASIP polymorphism was found
      not to be associated with MM or BCC. Stratified analysis showed that the
      association between MC1R mutations and the risk of MM and BCC was not
      significantly influenced by subjects' pigmentation characteristics or the 8818G
      ASIP variant. Further research is necessary, especially involving analysis of
      interactions between variation in MC1R and other genes, to find out if analysis
      of MC1R polymorphisms could be of any importance for skin cancer prevention.

PMID- 18637132
TI  - A study of a single variant allele (rs1426654) of the pigmentation-related gene
      SLC24A5 in Greek subjects.
AB  - The SLC24A5 gene, the human orthologue of the zebrafish golden gene, has been
      shown to play a key role in human pigmentation. In this study, we investigate the
      prevalence of the variant allele rs1426654 in a selected sample of Greek
      subjects. Allele-specific polymerase chain reaction was performed in peripheral
      blood samples from 158 attendants of a dermatology outpatient service. The
      results were correlated with pigmentary traits and MC1R genotype. The vast
      majority of subjects (99%) were homozygous for the Thr(111) allele. Only two
      subjects from the control group (1.26%) were heterozygous for the alanine and
      threonine allele. Both of these Thr(111)/Ala(111) heterozygotes carried a single
      polymorphism of MC1R (one with the V92M variant and another with the V60L
      variant). Following reports of the rs1426654 polymorphism reaching fixation in
      the European population, our study of Greek subjects showed a prevalence of the
      Thr(111) allele, even among subjects with darker skin pigmentation or phototype.

PMID- 18637133
TI  - Skin physiological parameters confirm the therapeutic efficacy of pimecrolimus
      cream 1% in patients with mild-to-moderate atopic dermatitis.
AB  - In this double-blind, within-patient vehicle-controlled study, patients with mild
      to-moderate atopic dermatitis (AD) were treated for 3 weeks twice daily with
      pimecrolimus cream 1% on one forearm and with vehicle cream on the other forearm.
      Efficacy of treatment was assessed clinically using the Atopic Dermatitis
      Severity Index (ADSI), the Investigators Global Assessment (IGA) and the pruritus
      visual analogue scale. In parallel, blood microcirculation in the skin was
      measured as an objective parameter for skin inflammation. Skin hydration and
      transepidermal water loss (TEWL) were monitored as parameter relevant for the
      barrier function. Treatment with pimecrolimus cream 1% resulted in a quick and
      marked improvement of signs and symptoms of AD and a significant reduction of
      microcirculation from 33.90 to 15.55 AU (P < 0.0001). Skin hydration increased
      continually from 42.86 to 52.69 AU (P = 0.002) and TEWL decreased from 35.30 to
      21.50 g/m(2)/h (P = 0.001), indicating restoration of skin barrier. At vehicle
      treated sites changes of skin physiological parameters were less pronounced and
      observed only initially with later plateau or even reversal. At the end of the
      study, there were significant differences for all measured skin physiological
      parameters between pimecrolimus cream 1% and vehicle: microcirculation 12.15 AU
      (P = 0.004), skin hydration 7.12 AU (P = 0.002), TEWL 11.38 g/m(2)/h (P = 0.004).
      Non-invasive evaluation of microcirculation and barrier functionality thus
      represent a valuable tool for the objective assessment of treatment response to
      pimecrolimus cream 1%.

PMID- 18637134
TI  - Computer-aided skin prick test.
AB  - The interpretation of the skin prick test is subject to inter-observer variation.
      To remove this variation, a computerized procedure for the skin prick test is
      suggested. Instead of manually measuring the emerging wheals, a series of
      photographs is automatically taken of the forearm. The photographs thus taken are
      then analyzed with a digital image processing algorithm to give the measurement
      results. The computerized test has the added benefit of being able to produce a
      time series for the wheal size. This makes it possible to see the onset time of
      the reaction in addition to the size of the wheal. Preliminary feasibility test
      suggests that the simple setup described in this letter is able to perform the
      skin prick test automatically and to show the kinetic behaviour of the wheal. The
      main challenges with the test setup are related to illumination and wheal
      detection algorithms.

PMID- 18637135
TI  - Predicting possible zonisamide hypersensitivity syndrome.
AB  - Zonisamide (ZNS) is an anticonvulsant (AC) that contains a sulpha moiety
      potentially triggering hypersensitivity syndrome reactions (HSR). The lymphocyte
      toxicity assay (LTA) is an in vitro drug rechallenge test, which is believed to
      reflect a decreased capacity of the individual to detoxify reactive metabolites.
      The study examined whether cross-reactivity is present between ZNS and other AC
      and/or sulphonamides and if this HSR may be predicted using the LTA. The second
      aim was to determine age-related differences in ZNS-induced HSR. LTA was
      previously validated in patients who received sulphamethoxazole (SMX) or AC.
      METHODS: Forty adult patients who displayed clinical HSR to SMX (20) or AC (20)
      participated in the study. Each group was represented with an equal number of
      individuals above and below the age of 60. LTA-SMX, LTA-AC and LTA-ZNS from 20
      patients who previously presented a clinical reaction to one of the drugs and who
      had a positive LTA result to the specific drug were compared with 20 individuals
      who received the same drugs but did not present reactions. Binary logistic
      regression was used to evaluate the statistical significance. RESULTS: In vitro
      results correlated with the clinical diagnosis. LTA presented a significant
      difference (P < 0.0001) between control and hypersensitive patients. In each age
      group, only a single patient had a severe clinical manifestation of SMX-HSR.
      These individuals tested positive to both SMX and ZNS. CONCLUSIONS:
      Sulphamethoxazole-HSR but not AC-HSR patients may present a cross-reactivity to
      ZNS-HSR. The use of LTA to predict a possible ZNS reaction is recommended for SMX
      sensitive individuals who prescribed ZNS.

PMID- 18637136
TI  - Molecular diagnosis of leishmaniosis in the Parana state of southern Brazil.
AB  - The objective of the present study was to establish a polymerase chain reaction
      (PCR) technique for the diagnosis of cutaneous and mucocutaneous leishmaniosis
      from autochthonous cases in the state of Parana in southern Brazil as well as
      imported cases. We sought to determine its utility and accuracy compared with
      smears and present culture methods. To standardize PCR samples, skin and mucosal
      punch biopsies from human lesions were performed on patients living in different
      regions of the Parana state (76 cases) and other endemic areas of Brazil and
      Argentina (7 cases). For PCR standardization, two pairs of primers (MP1L/MP3H and
      B1/B2) were utilized for amplification of the conserved sequences in the
      minicircle of kinetoplast DNA (kDNA) for the Leishmania braziliensis complex. Two
      other primer pairs (b1/b2 and a1/a2) were species-specific for L. (V.)
      braziliensis and L. (V.) amazonensis, respectively. After differential diagnosis,
      eight patients had clinical diagnosis of the cutaneous ulcer changed to others
      pathologies such as syphilis, baso-cellular carcinoma, varicose ulcer, ecthyma
      and paracoccidioidomycosis. Of the 75 patients with cutaneous (CL) and
      mucocutaneous (MCL) lesions who provided samples, 47 (46 CL + 1 MCL) were
      diagnosed with leishmaniosis by smear and 57 (52 LC + 5 MCL) were diagnosed by
      culture methods. In contrast, our PCR technique presented higher accuracy when
      compared to the direct examination and culture of parasites. PCR is applicable
      both for CL where all 61 lesions were diagnosed, and MCL where 12 of 14 lesions
      were diagnosed. This molecular biology technique is also a faster and more
      specific diagnostic method compared with present parasitological procedures.

PMID- 18637137
TI  - Production of fermentation aroma compounds by Saccharomyces cerevisiae wine
      yeasts: effects of yeast assimilable nitrogen on two model strains.
AB  - The contribution of yeast fermentation metabolites to the aromatic profile of
      wine is well documented; however, the biotechnological application of this
      knowledge, apart from strain selection, is still rather limited and often
      contradictory. Understanding and modeling the relationship between nutrient
      availability and the production of desirable aroma compounds by different strains
      must be one of the main objectives in the selection of industrial yeasts for the
      beverage and food industry. In order to overcome the variability in the
      composition of grape juices, we have used a chemically defined model medium for
      studying yeast physiological behavior and metabolite production in response to
      nitrogen supplementation so as to identify an appropriate yeast assimilable
      nitrogen level for strain differentiation. At low initial nitrogen
      concentrations, strain KU1 produced higher quantities of esters and fatty acids
      whereas M522 produced higher concentrations of isoacids, gamma-butyrolactone,
      higher alcohols and 3-methylthio-1-propanol. We propose that although strains KU1
      and M522 have a similar nitrogen consumption profile, they represent useful
      models for the chemical characterization of wine strains in relation to wine
      quality. The differential production of aroma compounds by the two strains is
      discussed in relation to their capacity for nitrogen usage and their impact on
      winemaking. The results obtained here will help to develop targeted metabolic
      footprinting methods for the discrimination of industrial yeasts.

PMID- 18637138
TI  - Posttransformational vector amplification in the yeast Pichia pastoris.
AB  - Generating a high yield of recombinant protein is a major goal when expressing a
      foreign gene in any expression system. In the methylotrophic yeast Pichia
      pastoris, a common means of achieving this end is to select for transformants
      containing multiple integrated copies of an expression vector by plating them on
      high levels of a selectable marker drug followed by screening for rare colonies
      with multiple copies. We describe a more convenient method to select for such
      clones. Using Zeocin-resistance-based vectors, we demonstrate that strains
      transformed with only one or a few vector copies can, long after transformation,
      be subjected to further selection at high levels of drug. This resulted in the
      frequent selection of clones containing increased copy numbers of the vector.
      This posttransformational vector amplification (PTVA) process resulted in strains
      containing multiple head-to-tail copies of the entire vector integrated at a
      single locus in the genome. Of our PTVA selected clones, 40% showed a three- to
      fivefold increase in vector copy number. So-called 'jackpot' clones with >10
      copies of the expression vector represented 5-6% of selected clones and had a
      proportional increase in recombinant protein.

PMID- 18637139
TI  - Evaluation of an internet-based disease trajectory decision tool for prostate
      cancer screening.
AB  - OBJECTIVE: To evaluate the application of a chronic disease model (CDM) for
      prostate cancer to visual analog scale (VAS) and time trade-off (TTO) decision
      tools. METHODS: A total of 138 men (mean age 58 years) viewed a CDM module for
      prostate cancer with and without prostate specific antigen (PSA) screening.
      Participants rated their hypothetical quality of life with potential prostate
      cancer treatment complications using a CDM-based VAS decision tool. They were
      then asked to estimate how many years they would be willing to trade to be free
      of treatment complications using a CDM-based TTO decision tool. The consistency
      between VAS and TTO scores and the relationship between scores and preferences
      for PSA screening test and hypothetical treatment choice for prostate cancer were
      then evaluated. RESULTS: There was a significant relationship between the VAS and
      TTO ratings (regression P < 0.001). The TTO tool was sensitive to age. Mean
      scores with standard deviations for those less than 58 years compared to those 58
      years and more were 7.78 (1.75) and 8.41 (1.52), respectively (P = 0.04). Using
      the VAS tool, men who chose PSA screening had higher quality of life ratings
      compared to men who did not choose PSA screening: 7.73 (1.78) and 6.59 (2.39),
      respectively (P = 0.01). Similar results were found with the TTO decision tool:
      8.33 (1.45) and 7.04 (2.00), respectively (P = 0.005). Men who would
      hypothetically prefer treatment for moderately differentiated prostate cancer
      also had higher TTO scores compared to men who preferred watchful waiting: 8.54
      (1.39) and 7.85 (1.73), respectively (P = 0.04). CONCLUSION: CDM-based for
      prostate cancer, VAS and TTO ratings were consistent and were concordant with
      patient preferences for screening; TTO ratings were also concordant with
      treatment choice. The use of the CDM-based TTO ratings to adjust for quality of
      life in decision analytic modeling needs to be explored.

PMID- 18637140
TI  - Mapping the EORTC QLQ C-30 onto the EQ-5D instrument: the potential to estimate
      QALYs without generic preference data.
AB  - OBJECTIVES: The aim of this article is to map the European Organization for
      Research and Treatment of Cancer (EORTC) QLQ C-30 onto the EQ-5D measure to
      enable the estimation of health state values based on the EORTC QLQ C-30 data.
      The EORTC QLQ C-30 is of interest because it is the most commonly used instrument
      to measure the quality of life of cancer patients. METHODS: Regression analysis
      is used to establish the relationship between the two instruments. The
      performance of the model is assessed in terms of how well the responses to the
      EORTC QLQ C-30 predict the EQ-5D responses for a separate data set. RESULTS: The
      results showed that the model explaining EQ-5D values predicted well. All of the
      actual values were within the 95% confidence intervals of the predicted values.
      More importantly, predicted difference in quality-adjusted life-years (QALYs)
      between the arms of the trial was almost identical to the actual difference.
      CONCLUSION: There is potential to estimate EQ-5D values using responses to the
      disease-specific EORTC QLQ C-30 measure of quality of life. Such potential
      implies that in studies that do not include disease-specific measures, it might
      still be possible to estimate QALYs.

PMID- 18637141
TI  - Budgetary impact of varenicline in smoking cessation in the United Kingdom.
AB  - OBJECTIVES: To estimate the budgetary impact of varenicline in the United Kingdom
      (UK) in the first 5 years after its introduction to the smoking-cessation aid
      market, from the National Health Service (NHS) pharmacy perspective. METHODS: The
      economic impact of varenicline to the national health budget is estimated in a
      population of current, former, and new smokers. The analyses are based on data
      from a variety of secondary sources including national health data, clinical
      trials, and meta-analyses of smoking-cessation aids. The number of patients
      seeking aid and the treatment patterns are estimated using 2004 national health
      surveys, costs for medications from national prescription drug pricing tariffs,
      and efficacy of the various smoking-cessation aids from clinical trial data.
      Sensitivity analyses were performed to evaluate the impact of varying the patient
      parameters and costs. RESULTS: Model estimates suggest that the budgetary impact
      of varenicline would be 3.6 million pound in the second year after its
      introduction, with a 95% confidence interval of 0.63 to 7.2 million pound, and a
      resultant increase of 0.05% to the total NHS pharmacy budget. The model predicts
      that the addition of varenicline to the market would result in an additional
      162,000 successful smoking-cessation attempts and 103,000 fewer smokers over 5
      years, when compared to the world without varenicline. CONCLUSION: The
      introduction of varenicline is likely to result in greater numbers of individuals
      succeeding at smoking cessation, with an approximately 3.6 million pound (0.05%)
      increase in the NHS pharmacy budget.

PMID- 18637142
TI  - Satisfaction and adherence in patients with iron overload receiving iron
      chelation therapy as assessed by a newly developed patient instrument.
AB  - OBJECTIVES: This study assesses satisfaction with iron chelation therapy (ICT)
      based on a reliable and valid instrument, and explores the relationship between
      satisfaction and adherence to ICT. METHODS: Patients in the USA and UK completed
      a new "Satisfaction with ICT" (SICT) instrument consisting of 28 items, three
      pertaining to adherence. Simple and multivariate regression analyses assessed the
      relationship between satisfaction with different aspects of ICT and adherence.
      RESULTS: First assessments of the SICT instrument indicate its validity and
      reliability. Recommended thresholds for internal consistency, convergent
      validity, discriminant validity, and floor and ceiling effects were met. A number
      of variables were identified in the simple linear regression analyses as
      significant predictors of "never thinking about stopping ICT," a proxy for
      adherence. These significant variables were entered into the multivariate model
      to assess the combined factor effects, explaining 42% of the total variance of
      "never thinking about stopping ICT." A significant and positive relationship was
      demonstrated between "never thinking about stopping ICT" and age (P = 0.04),
      Perceived Effectiveness of ICT (P = 0.003), low Burden of ICT (P = 0.002), and
      low Side Effects of ICT (P = 0.01). CONCLUSIONS: The SICT is a reliable and valid
      instrument which will be useful in ICT clinical trials. Furthermore, the
      administration of ICT by slow subcutaneous infusion negatively impacts on
      satisfaction with ICT which was shown to be a determinant of adherence. This
      points to the need for new more convenient and less burdensome oral iron
      chelators to increase adherence, and ultimately to improve patient outcomes.

PMID- 18637143
TI  - Hepatocyte growth factor gene transfer with naked plasmid DNA ameliorates
      dimethylnitrosamine-induced liver fibrosis in rats.
AB  - AIM: Hepatocyte growth factor (HGF) has various biological properties, including
      antifibrogenic activity. In the present study, we tested the efficacy of HGF gene
      therapy using naked plasmid DNA in dimethylnitrosamine (DMN)-induced liver
      fibrosis in a rat model. METHODS: Naked plasmid DNA encoding human HGF was
      injected once, together with a hypertonic solution, into the hepatic artery after
      DMN treatment on three consecutive days per week for 3 weeks. Naked plasmid DNA
      encoding beta-galactosidase was injected similarly in the DMN-treated control
      rats. DMN treatment was continued once weekly after gene transfer for additional
      3 weeks. RESULTS: The human HGF protein expression was detected in livers
      transfected with human HGF naked plasmid DNA, gradually decreasing by day 21. The
      expression of the endogenous rat HGF protein was also upregulated after human HGF
      gene transfer. Phosphorylation of c-Met, a HGF receptor, was detected only in
      livers transfected with human HGF plasmid DNA. Fibrosis was attenuated
      significantly in livers transfected with the human HGF plasmid. Attenuation
      wasaccompanied by decreased expression of alpha-smooth muscle actin. Increased
      portal vein pressure after treatment with DMN was suppressed significantly by HGF
      gene transfer. The upregulated hepatic protein expression of transforming growth
      factor-beta (TGF-beta) in response to DMN was markedly attenuated by HGF gene
      transfer accompanied by the increased protein expression for matrix
      metalloproteinases (MMP)-3 and -13. CONCLUSION: The hepatic arterial injection of
      human naked plasmid HGF DNA was effective in suppressing liver fibrosis induced
      in rats by DMN. The mechanisms by which HGF expression attenuated liver fibrosis
      may include the suppression of hepatic TGF-beta expression and the induction of
      MMP expression.

PMID- 18637144
TI  - Recent status of drug-induced liver injury.
AB  - Drug-induced liver injury is an major cause of acute liver injury and the
      incidence of drug-induced liver injury seems to be increasing with an increase in
      the number of new drugs available. The diagnostic scale of drug-induced liver
      injury was been modified by the International Consensus Meeting during Digestive
      Disease Week, Japan 2004, which includes the score of the drug-lymphocyte
      stimulation test and eosinophilia. Although the modified diagnostic scale is
      useful, and widely used in Japan, there will be many issues to be investigated in
      the future. According to a recent survey of drug-induced liver injury cases in
      Japan, drug-induced liver injury from dietary supplements are increasing, as has
      been observed in foreign countries. More research is needed to elucidate the
      mechanisms of drug metabolism and the pathophysiology of liver injury by various
      drugs to prevent drug-induced liver injury.

PMID- 18637145
TI  - Gene expression profiling of non-alcoholic steatohepatitis using gene set
      enrichment analysis.
AB  - AIM: Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty
      liver disease (NAFLD) and sometimes progresses to cirrhosis and liver failure. In
      this study we analyzed the expression profile of genes and biological pathways
      involved in NASH in comparison with non-NASH by gene set enrichment analysis
      (GSEA) employing a DNA microarray technique. METHODS: mRNA from liver biopsy
      specimens was collected from a group of NASH patients and a group of non-NASH
      patients. We analyzed the relative abundance of mRNA using high-density
      oligonucleotide microarrays containing probes for 54 675 known genes, and
      investigated the pathogenetic mechanisms of NASH by means of a powerful technique
      for analyzing molecular profiling data, GSEA. RESULTS: The results showed that
      the level of expression of 27 gene sets was significantly higher and the level of
      expression of 25 gene sets was significantly lower in the NASH samples than in
      the non-NASH samples. Based on these results we created an online, publicly
      available, searchable database containing the data for the gene expression
      profiles of the NASH patients (http://www2.genome.rcast.u
      tokyo.ac.jp/___/NASH/NASH_GSEA2/). CONCLUSION: Our data revealed differences in
      expression of many gene sets that are involved in the pathogenesis of NASH.

PMID- 18637146
TI  - Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout
      mice.
AB  - AIM: Nonalcoholic fatty liver disease (NAFLD) represents a growing health concern
      due to its rapidly increasing prevalence worldwide. Nonalcoholic steatohepatitis
      (NASH) is a progressing form of NAFLD, and recently many studies have reported
      that it could eventually develop into hepatocellular carcinoma (HCC). We
      previously reported that 6-month-old male galectin-3 knockout (gal3(-/-)) mice
      developed clinicopathological features similar to those of NAFLD in humans. Our
      aim was to investigate the changes in liver histology in gal3(-/-) mice by long
      term observation. METHODS: We initially investigated three 15-month-old gal3(-/-)
      mice, of which two developed multiple liver nodules with dysplastic changes.
      Then, we histopathologically examined the liver specimens of the 15-, 20- and 25
      month-old gal3(-/-) mice and attempted to evaluate the liver morphology by
      contrast enhanced computed tomography (CT) before sacrifice. RESULTS: At the age
      of 15 months or later, gal3(-/-) mice developed liver nodules with varying
      degrees of architectural and nuclear atypia based on mild to moderate delicate
      zone 3 fibrosis. In addition, we successfully confirmed the presence of some of
      the liver nodules by CT. We report herein that gal3(-/-) mice develop dysplastic
      liver nodules and HCC. CONCLUSIONS: We believe that it would be interesting to
      use this murine model to investigate liver carcinogenesis based on a natural
      history of NAFLD. Furthermore, CT scanning might be a useful tool for
      longitudinal evaluation of morphological changes in vivo.

PMID- 18637147
TI  - Cell survival, activation and apoptosis of hepatic stellate cells: modulation by
      extracellular matrix proteins.
AB  - AIM: Cytokines and growth factors released by various hepatic cells exert both
      paracrine and autocrine effects on hepatic stellate cell (HSC) activation during
      liver injury. The aim of the present study was to examine whether the surrounding
      extracellular matrix (ECM) influences the activation, transdifferentiation and
      survival of HSCs. METHODS: An in vitro model system of isolated HSCs maintained
      in culture on different matrix protein substrata was employed. RESULTS: The rate
      of loss of HSC-specific retinol uptake activity and gain of myofibroblast-like
      activity such as (35)[S] proteoglycan synthesis varied in cells maintained on
      different matrix proteins and was in the order collagen I > collagen IV >/=
      laminin. (3)[H]-thymidine incorporation by HSCs maintained on different matrix
      proteins varied and was in the order collagen I > collagen IV > laminin. MTT
      assay revealed that the growth inhibition in response to curcumin was
      significantly low in cells maintained on collagen I. Apoptotic marker activities
      such as DNA fragmentation, 4',6'-diamidino-2-phenylindole dihydrochloride (DAPI)
      staining, annexin staining and caspase-3 activities showed that cells maintained
      on collagen I showed minimal apoptosis than those maintained on collagen IV,
      laminin and polylysine, showing the influence of ECM on HSC apoptosis.
      Experiments using blocking antibodies showed that the collagen I effect was
      mediated through alpha(2)beta(1) integrin. CONCLUSIONS: These results indicate
      that ECM influences activation, transdifferentiation and survival of HSCs, and
      suggest that apart from diffusible factors, the surrounding ECM also influences
      HSC behavior critical in both the progression of the fibrosis and the restitution
      of the liver during recovery after hepatic injury.

PMID- 18637148
TI  - Recent developments in vulvovaginal pathology.
AB  - This review discusses recent developments in vulvovaginal pathology. A variety of
      morphologically bland mesenchymal lesions occur at this site with considerable
      histological and immunohistochemical overlap. Aggressive angiomyxoma exhibits
      HMGA2 immunoreactivity in approximately 50% of cases, and this nuclear
      transcription factor is emerging as a useful and relatively specific marker for
      aggressive angiomyxoma, although occasional vulvovaginal smooth muscle neoplasms
      are positive. HMGA2 is useful in the diagnosis of aggressive angiomyxoma and its
      distinction from mimics, in the evaluation of resection margins and in the
      assessment of the presence or absence of residual disease in re-excisions.
      Aggressive angiomyxoma is almost invariably positive with oestrogen and
      progesterone receptors, and there have been several reports of a dramatic
      reduction in size following gonadotropin releasing hormone agonist therapy.
      Recent series of the relatively newly described entities cellular angiofibroma
      and superficial myofibroblastoma of the lower female genital tract have expanded
      upon the morphological spectrum of these neoplasms. Recently described
      mesenchymal lesions at this site include massive oedema and prepubertal vulval
      fibroma. Gastrointestinal stromal tumours have been described as primary
      neoplasms in the vagina, and rectovaginal septum and extragastrointestinal
      stromal tumour should be added to the differential diagnosis of a vulvovaginal
      mesenchymal lesion. Many mesenchymal lesions in the vulvovaginal region exhibit
      immunoreactivity with both CD34 and desmin, a somewhat unusual immunophenotype in
      mesenchymal lesions at other sites. It is now established that there are two
      distinct types of vulval intraepithelial neoplasia (VIN), most commonly termed
      classic and differentiated VIN, the former associated with human papillomavirus
      (HPV) infection. There are two corresponding types of vulval squamous carcinoma
      with HPV-associated and non-HPV-associated variants, the latter often arising in
      a vulval dystrophy and associated with p53 mutation. However, in some cases there
      is clinicopathological overlap between HPV-associated and non-HPV-associated
      squamous carcinomas, and immunohistochemistry with p16 is more reliable than
      morphology in predicting the presence of HPV. There have been new developments
      regarding Paget's disease of the vulva with the identification of markers that
      are useful in diagnosis and evidence that the neoplastic cells represent a
      proliferation of adnexal stem cells residing in sebaceous units. The newly
      described entity vaginal tubulo-squamous polyp typically exhibits
      immunopositivity with prostatic markers, possibly indicating derivation from
      displaced periurethral Skene's glands.

PMID- 18637149
TI  - Lesions of the jaws.
AB  - The jaws differ in various aspects from all other bones in the skeleton.
      Embryologically, they are for the major part derived from migrating cells of the
      cranial neural crest, the so-called ectomesenchyme, and not merely from mesoderm,
      and they contain teeth. This latter point, especially, results in the presence of
      lesions that are not found in other bones, a broad variety of odontogenic cysts
      and tumours. They will be the major topic of this review. Other lesions, not
      strictly odontogenic but also mainly confined to the jaw bones, are giant cell
      lesions, fibro-osseous lesions, and the melanotic neuro-ectodermal tumour of
      infancy. They also will be included in this overview.

PMID- 18637150
TI  - Is hypospadias a genetic, endocrine or environmental disease, or still an
      unexplained malformation?
AB  - Hypospadias is one of the most frequent genital malformations in the male newborn
      and results from an abnormal penile and urethral development. This process
      requires a correct genetic programme, time- and space-adapted cellular
      differentiation, complex tissue interactions, and hormonal mediation through
      enzymatic activities and hormonal transduction signals. Any disturbance in these
      regulations may induce a defect in the virilization of the external genitalia and
      hypospadias. This malformation thus appears to be at the crossroads of various
      mechanisms implicating genetic and environmental factors. The genes of penile
      development (HOX, FGF, Shh) and testicular determination (WT1, SRY) and those
      regulating the synthesis [luteinizing hormone (LH) receptor] and action of
      androgen (5alpha reductase, androgen receptor) can cause hypospadias if altered.
      Several chromosomal abnormalities and malformative syndromes include hypospadias,
      from anterior to penoscrotal forms. More recently, CXorf6 and ATF3 have been
      reported to be involved. Besides these genomic and hormonal factors, multiple
      substances found in the environment can also potentially interfere with male
      genital development because of their similarity to hormones. The proportion of
      hypospadias cases for which an aetiology is detected varies with the authors but
      it nevertheless remains low, especially for less severe cases. An interaction
      between genetic background and environment is likely.

PMID- 18637151
TI  - A Rotterdam controversy: the aetiology of the cryptorchid hypothalamo-pituitary
      testicular axis.

PMID- 18637152
TI  - Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and
      prostate carcinoma.
AB  - 7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than
      testosterone (T) and cannot be reduced at 5-alpha position. No important effects
      of MENT on prostate growth have been reported. However, little is known about the
      effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP).
      We evaluate the effect of MENT, T and dihydrotestosterone (DHT) on secretion,
      proliferation and gene expression of primary cell cultures from human BPH and
      CaP. Moreover, the effect of these androgens was examined in the presence of
      finasteride to determine the influence of the 5-alpha reductase (5-AR) activity
      on the androgenic potency. BPH and CaP primary cultures were treated with 0, 1,
      10 and 100 nM of T, MENT or DHT during 24 and 48 h. Prostate-specific antigen
      (PSA) was measured by micro particles immunoassay and proliferation rate by
      spectrophotometric assay (MTT) and by the immunochemical detection of the
      proliferation marker Ki-67. Gene expression of FGF8b (androgen sensitive gene)
      was evaluated by semi-quantitative RT-PCR. Results showed that MENT treatments
      increased PSA secretion and proliferation rate with a potency ranged between T
      and DHT. Similar effects of MENT were observed in both BPH and CaP cultures. The
      studies with finasteride showed that in BPH and CaP cells, the conversion of T
      into DHT significantly contributes to its effect on the proliferation and PSA
      secretion, and corroborated the resistance of MENT to the 5-AR. The effect of
      MENT on the gene expression of FGF8b in CaP cells was similar to T and lower than
      DHT. It is concluded that MENT increases proliferative and secretory activities
      and gene expression on pathological prostate cells although in less extent than
      the active metabolite DHT. Furthermore, the fall of endogenous concentration of T
      during MENT treatment anticipates that this androgen will be of low impact for
      the prostate.

PMID- 18637153
TI  - Epigenetic regulation and downstream targets of the Rhox5 homeobox gene.
AB  - The discovery of the Rhox homeobox gene cluster on the X chromosome opens up new
      vistas in the regulation of reproductive processes in mammals. In mice, this
      cluster comprises more than 30 genes that are selectively expressed in
      reproductive tissues. A subset of Rhox genes are androgen and AR regulated in
      postnatal and adult Sertoli cells, making them candidates to mediate androgen
      dependent steps during spermatogenesis. The best characterized of these
      androgen/AR-regulated genes is Rhox5 (Pem), the founding member of the Rhox gene
      cluster. Targeted deletion of Rhox5 in mice causes male subfertility marked by
      increased germ-cell apoptosis and decreased sperm count and motility. Microarray
      analyses identified a wide variety of genes regulated by Rhox5 in Sertoli cells.
      One of them is the tumour suppressor UNC5C, a pro-apoptotic molecule previously
      only known to be involved in brain development. Targeted deletion of Unc5c causes
      decreased germ-cell apoptosis in postnatal and adult testes, indicating that it
      also has a role in spermatogenesis and supporting a model in which Rhox5 promotes
      germ-cell survival by downregulating Unc5c. Rhox5 has two independently regulated
      promoters that have distinct expression patterns. The unique tissue-specific and
      developmentally regulated transcription pattern of these two promoters appear to
      be controlled by DNA methylation. Both promoters are methylated in tissues in
      which they are not expressed, suggesting that DNA methylation serves to repress
      Rhox5 expression in inappropriate cell types and tissues. In summary, the Rhox
      gene cluster is an epigenetically regulated set of genes encoding a large number
      of transcription factors that are strong candidates to regulate gametogenesis and
      other aspects of reproduction.

PMID- 18637154
TI  - The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on foetal male rat
      steroidogenesis.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic and widely
      investigated dioxin congener. In utero and lactational exposure to TCDD results
      in developmental and reproductive defects that are the most sensitive endpoints
      for TCDD toxicity. TCDD has a potential to interfere with steroid metabolism, but
      the mechanisms by which this occurs are not well understood. In this study, we
      investigated the effects of TCDD on prenatal rat steroidogenesis. Pregnant
      Sprague-Dawley female rats were treated once with TCDD (0, 0.3 or 1 microg/kg) by
      gavage on embryonic day (ED) 11 and the expression levels of androgen (AR) and
      estrogen receptors (ER), steroidogenic enzymes (P450scc and 3beta-HSD) and four
      regulatory factors (StAR, SF-1, GATA-4 and Insl-3) involved in foetal Leydig cell
      and adrenal function were analysed on ED 19.5. Hormonal status of male foetuses
      was determined by measuring testicular testosterone (T) levels, plasma
      luteinizing hormone (LH) and corticosterone concentrations. In utero exposure to
      TCDD reduced intratesticular T of foetal males (significant at 0.3 microg/kg
      TCDD) and tended to reduce the protein expression of ERalpha and AR of foetal
      male rat testis. Foetal male rat plasma LH levels were significantly reduced at
      the dose of 1 microg/kg TCDD, while corticosterone levels tended to be increased
      possibly because of the TCDD-induced stress. Only minor alterations in
      steroidogenesis were observed in rat adrenal. mRNA expression of developmental
      regulatory factors was not influenced by foetal TCDD exposure, except for
      significantly reduced adrenal SF-1. The results demonstrate that maternal
      exposure to TCDD suppressed testicular steroidogenesis of 19.5-day-old foetal
      male Sprague-Dawley rat. The highest dose of TCDD (1 microg/kg) had also an
      effect on pituitary LH secretion. Our data implicate that TCDD has direct
      testicular and pituitary effects on foetal male rat but with different dose
      responses. These changes can lead to impaired steroidogenesis and it may result
      in the maldevelopment of the testis and weaken masculinization.

PMID- 18637155
TI  - Carbamazepine damage to rat spermatogenesis in different sexual developmental
      phases.
AB  - Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also
      utilized for treatment of psychiatric disorders and neuropathic pain. The
      utilization of CBZ has been associated with damage to male reproduction including
      hormonal alterations, sexual dysfunction and reduction of sperm quality. Wide and
      long-term use of CBZ has been a common schedule for children and adolescents,
      despite the fact it alters the testosterone level in adult rats and humans. In
      addition, hypothalamic-pituitary-gonadal (HPG) axis during pre-puberty and
      puberty is more susceptible to toxic agents than in adult phase. The objective of
      this work was to evaluate the side effects of CBZ on the spermatogenic process of
      rats from pre-puberty to puberty and sexual maturation. Damage on the
      seminiferous epithelium, testicular interstitial oedema, reductions of
      testosterone levels and an increase in oestradiol levels were observed in rats,
      which were CBZ-treated since the weaning. The results suggest that CBZ, when
      administered from pre-puberty, provokes specific side effects on rat testes,
      resulting in more severe damage in the adult phase.

PMID- 18637156
TI  - A randomized, double-blind, placebo-controlled phase II dose-finding study of the
      novel anti-muscarinic agent imidafenacin in Japanese patients with overactive
      bladder.
AB  - OBJECTIVES: To evaluate the efficacy, safety/tolerability, and dose-response
      relationship of imidafenacin in Japanese patients with overactive bladder.
      METHODS: Men and women who had overactive bladder symptoms were randomized
      equally to double-blind treatment with 0.05, 0.1, or 0.25 mg of imidafenacin
      twice daily or a placebo for 12 weeks, and assessed for efficacy and safety.
      RESULTS: Overall, 401 patients were enrolled and randomized for treatment with
      0.1 mg of imidafenacin/day (99 patients), 0.2 mg of imidafenacin/day (100), 0.5
      mg of imidafenacin/day (101), or a placebo (101). After 12 weeks of treatment,
      the number of incontinence episodes was reduced in a dose-dependent manner, and a
      significant difference between the imidafenacin treatment and the placebo was
      observed (P < 0.0001). Compared with the placebo, imidafenacin caused significant
      reductions in urgency incontinence, voiding frequency, and urinary urgency, and a
      significant increase in the urine volume voided per micturition. Imidafenacin was
      also well tolerated. The incidence of dry mouth in the imidafenacin groups
      increased dose-dependently. Even though the percentage of patients receiving 0.5
      mg/day who discontinued treatment due to dry mouth was high (8.9%), the
      percentages in the 0.1 mg/day and 0.2 mg/day groups (1.0% and 0.0%, respectively)
      were comparable with that in the placebo group (0.0%). CONCLUSIONS: Considering
      the balance between efficacy and safety, 0.1 mg of imidafenacin twice daily
      appeared to be a clinically appropriate dose for treating overactive bladder.
      This dose was therefore selected for further evaluation in large-scale phase III
      studies.

PMID- 18637157
TI  - Epidemiology of urogenital tuberculosis worldwide.
AB  - OBJECTIVES: To characterize the epidemiology of urogenital tuberculosis worldwide
      and to compare the features of patients from developing countries to those from
      developed countries. METHODS: A comprehensive search of articles published up to
      April 2008 using a combination of the terms 'tuberculosis', 'genitourinary',
      'renal' and 'urogenital' was performed. RESULTS: Urogenital tuberculosis affects
      more men than women (2:1), with a mean age of 40.7 years (range 5-90). In 26.9%
      of cases there is a non-functioning unilateral kidney and in 7.4%, renal failure.
      Patients from developing countries are more likely to have a delayed diagnosis
      with a higher frequency of renal failure, unilateral non-functioning kidney,
      ablative surgery and contracted bladder. CONCLUSIONS: Urogenital tuberculosis is
      a worldwide disease with more destructive behavior in developing countries where
      urgent strategies for early detection are particularly warranted.

PMID- 18637158
TI  - Influence of hospital and surgeon volumes on operative time, blood loss and
      perioperative complications in radical nephrectomy.
AB  - OBJECTIVES: We conducted a nationwide multi-center survey using medical record
      based data to investigate the relationship between hospital/surgeon volumes and
      various outcomes, including operative time, volume of blood loss, and incidence
      of perioperative complications, in radical nephrectomy for renal cell carcinoma.
      METHODS: We investigated a total of 1704 patients who underwent radical
      nephrectomy at 461 hospitals in Japan between November 2006 and February 2007.
      The association between hospital/surgeon volumes and operative time, volume of
      blood loss, and incidence of perioperative complications were independently
      analyzed using multivariate regression analysis against age, gender, operation
      site, cancer stage, serum creatinine levels, comorbid conditions, and surgical
      technique (open surgery or minimally invasive surgery). RESULTS: Neither hospital
      volume nor surgeon volume was a significant predictor of operative time or volume
      of blood loss. We did not identify any association between hospital volume and
      perioperative complications. High-volume (> 100) surgeons were unlikely to have
      perioperative complications compared to low-volume (< 20) surgeons, but the
      relation was not significant (odds ratio, 0.50; 95% confidence intervals, 0.14
      1.87; P = 0.30). CONCLUSIONS: Volume-outcome relationships were not confirmed for
      radical nephrectomy. According to our study, the justification of regionalizing
      radical nephrectomy to centers of excellence is not yet clear.

PMID- 18637159
TI  - Changes of bladder activity and glycine levels in the lumbosacral cord after
      partial bladder outlet obstruction in rats.
AB  - OBJECTIVES: We investigated the time course of changes in bladder activity as
      well as in spinal and serum levels of glutamate and glycine after partial bladder
      outlet obstruction (BOO) in rats. METHODS: A total of 36 female rats were divided
      into six groups: sham operation (control); 3 days, 14 days, and 28 days after
      BOO; 3 days and 28 days after relief of BOO. Under urethane anesthesia,
      isovolumetric cystometry was carried out in each group. Then, spinal and serum
      levels of glutamate and glycine were measured. RESULTS: The interval between
      bladder contractions was shorter in all of the groups compared with the control
      group. The amplitude and duration of bladder contractions was decreased at 3
      days, 14 days, and 28 days after BOO, and at 3 days after relief of BOO. Spinal
      and serum glutamate levels showed no changes. However, the spinal glycine level
      was decreased at 14 days and 28 days after BOO, and at 28 days after relief of
      BOO. Serum glycine level was also decreased at 28 days after BOO and 28 days
      after relief of BOO. CONCLUSIONS: Detrusor overactivity during the chronic phase
      of partial BOO is partly caused by a decrease of glycinergic neuronal activity in
      the lumbosacral cord. A 3-day period of BOO produces detrusor overactivity, which
      might be due to an irreversible decrease of spinal glycinergic neuronal activity.

PMID- 18637160
TI  - Molecular characterisation of Mycobacterium bovis isolated from cattle
      slaughtered at the Bamako abattoir in Mali.
AB  - BACKGROUND: Mali is one of the most important livestock producers of the Sahel
      region of Africa. A high frequency of bovine tuberculosis (BTB) has been reported
      but surveillance and control schemes are restricted to abattoir inspections only.
      The objective of this study was to conduct, for the first time, molecular
      characterisation of Mycobacterium bovis strains isolated from cattle slaughtered
      at the Bamako abattoir. Of 3330 animals screened only 60 exhibited gross visible
      lesions. From these animals, twenty strains of M. bovis were isolated and
      characterised by spoligotyping. RESULTS: Organ lesions typical of BTB were most
      often detected in the liver, followed by the lung and the peritoneum. M. bovis
      was isolated from 20 animals and 7 different spoligotypes were observed among
      these 20 strains; three of the patterns had not been previously reported.
      Spoligotype patterns from thirteen of the strains lacked spacer 30, a
      characteristic common in strains of M. bovis found in Chad, Cameroon and Nigeria.
      However, unlike the other three Central African countries, the majority of
      spoligotype patterns observed in Mali also lacked spacer 6. Of the remaining
      seven strains, six had spoligotype patterns identical to strains commonly
      isolated in France and Spain. CONCLUSION: Two groups of M. bovis were detected in
      cattle slaughtered at the Bamako abattoir. The spoligotype pattern of the first
      group has similarities to strains previously observed in Chad, Cameroon and
      Nigeria. The additional absence of spacer 6 in the majority of these strains
      suggests a Mali specific clone. The spoligotype patterns of the remaining strains
      suggest that they may have been of European origin.

PMID- 18637161
TI  - WildSilkbase: an EST database of wild silkmoths.
AB  - BACKGROUND: Functional genomics has particular promise in silkworm biology for
      identifying genes involved in a variety of biological functions that include:
      synthesis and secretion of silk, sex determination pathways, insect-pathogen
      interactions, chorionogenesis, molecular clocks. Wild silkmoths have hardly been
      the subject of detailed scientific investigations, owing largely to non
      availability of molecular and genetic data on these species. As a first step, in
      the present study we generated large scale expressed sequence tags (EST) in three
      economically important species of wild silkmoths. In order to make these
      resources available for the use of global scientific community, an EST database
      called 'WildSilkbase' was developed. DESCRIPTION: WildSilkbase is a catalogue of
      ESTs generated from several tissues at different developmental stages of 3
      economically important saturniid silkmoths, an Indian golden silkmoth, Antheraea
      assama, an Indian tropical tasar silkmoth, A. mylitta and eri silkmoth, Samia
      cynthia ricini. Currently the database is provided with 57,113 ESTs which are
      clustered and assembled into 4,019 contigs and 10,019 singletons. Data can be
      browsed and downloaded using a standard web browser. Users can search the
      database either by BLAST query, keywords or Gene Ontology query. There are
      options to carry out searches for species, tissue and developmental stage
      specific ESTs in BLAST page. Other features of the WildSilkbase include cSNP
      discovery, GO viewer, homologue finder, SSR finder and links to all other related
      databases. The WildSilkbase is freely available from
      http://www.cdfd.org.in/wildsilkbase/. CONCLUSION: A total of 14,038 putative
      unigenes was identified in 3 species of wild silkmoths. These genes provide
      important resources to gain insight into the functional and evolutionary study of
      wild silkmoths. We believe that WildSilkbase will be extremely useful for all
      those researchers working in the areas of comparative genomics, functional
      genomics and molecular evolution in general, and gene discovery, gene
      organization, transposable elements and genome variability of insect species in
      particular.

PMID- 18637162
TI  - Regional variations in Paneth cell antimicrobial peptide expression along the
      mouse intestinal tract.
AB  - BACKGROUND: Enteric antimicrobial peptides secreted from Paneth cells, including
      alpha-defensins (in mice named cryptdins), are key effector molecules of innate
      immunity in the small intestine. The importance of Paneth cells alpha-defensins
      emerged from studies of enteric bacterial infection in genetically modified mice,
      as well as from recent studies linking reduced levels of these alpha-defensins to
      Crohn's disease localized to the ileum. However, analysis of expression of Paneth
      cell alpha-defensins is incomplete. We therefore performed a comprehensive
      evaluation of the distribution of antimicrobial molecules along the mouse small
      intestinal tract to identify potential variations in regional expression.
      RESULTS: In conventionally reared mice, the repertoire of Paneth cell
      antimicrobials differs between duodenum and ileum. In contrast to the uniform
      expression of most Paneth cell antimicrobials, both cryptdin 4 and cryptdin
      related sequences (CRS) 4C peptides were expressed at progressively increasing
      amounts (101- and 104-fold, respectively) comparing duodenum and ileum. In
      tissues other than the small intestine, expression of CRS peptides was noted in
      thymus and caecum. Most Paneth cell products were also produced in the small
      intestine of germ-free mice at levels similar to those in controls, however CRS4C
      and RegIIIgamma had reduced levels in the former (3- and 8-fold, respectively).
      No significant changes in expression levels of Paneth cell antimicrobial peptides
      was observed after oral challenge with either Salmonella enterica serovar
      typhimurium or Listeria monocytogenes, supporting current notions on the
      constitutive nature of this defensive system. CONCLUSION: The repertoire of
      antimicrobial peptides changes along the small intestinal tract, and a subset of
      these molecules are up-regulated upon colonization, but not in response to
      enteric bacterial pathogens. The changes detected upon colonization suggest that
      Paneth cell antimicrobial peptides may play an important role in commensal
      microbial homeostasis, in addition to their proposed role in protection against
      infection. In addition, the differential expression of CRS4C along the small
      intestine suggests mechanisms of regulation that are distinct from other Paneth
      cell derived antimicrobial peptides.

PMID- 18637164
TI  - Study of the collagen structure in the superficial zone and physiological state
      of articular cartilage using a 3D confocal imaging technique.
AB  - INTRODUCTION: The collagen structure in the superficial zone of articular
      cartilage is critical to the tissue's durability. Early osteoarthritis is often
      characterized with fissures on the articular surface. This is closely related to
      the disruption of the collagen network. However, the traditional histology can
      not offer visualization of the collagen structure in articular cartilage because
      it uses conventional optical microscopy that does not have insufficient imaging
      resolution to resolve collagen from proteoglycans in hyaline articular cartilage.
      This study examines the 3D collagen network of articular cartilage scored from 0
      to 2 in the scoring system of International Cartilage Repair Society, and aims to
      develop a 3D histology for assessing early osteoarthritis. METHODS: Articular
      cartilage was visually classified into five physiological groups: normal
      cartilage, aged cartilage, cartilage with artificial and natural surface
      disruption, and fibrillated. The 3D collagen matrix of the cartilage was acquired
      using a 3D imaging technique developed previously. Traditional histology was
      followed to grade the physiological status of the cartilage in the scoring system
      of International Cartilage Repair Society. RESULTS: Normal articular cartilage
      contains interwoven collagen bundles near the articular surface, approximately
      within the lamina splendens. However, its collagen fibres in the superficial zone
      orient predominantly in a direction spatially oblique to the articular surface.
      With age and disruption of the articular surface, the interwoven collagen bundles
      are gradually disappeared, and obliquely oriented collagen fibres change to align
      predominantly in a direction spatially perpendicular to the articular surface.
      Disruption of the articular surface is well related to the disappearance of the
      interwoven collagen bundles. CONCLUSION: A 3D histology has been developed to
      supplement the traditional histology and study the subtle changes in the collagen
      network in the superficial zone during early physiological alteration of
      articular cartilage. The fibre confocal imaging technology used in this study has
      allowed developing confocal arthroscopy for in vivo studying the chondrocytes in
      different depth of articular cartilage. Therefore, the current study has
      potential to develop an in vivo 3D histology for diagnosis of early
      osteoarthritis.

PMID- 18637163
TI  - Quantitative analysis of changes in actin microfilament contribution to cell
      plate development in plant cytokinesis.
AB  - BACKGROUND: Plant cells divide by the formation of new cross walls, known as cell
      plates, from the center to periphery of each dividing cell. Formation of the cell
      plate occurs in the phragmoplast, a complex structure composed of membranes,
      microtubules (MTs) and actin microfilaments (MFs). Disruption of phragmoplast MTs
      was previously found to completely inhibit cell plate formation and expansion,
      indicative of their crucial role in the transport of cell plate membranes and
      materials. In contrast, disruption of MFs only delays cell plate expansion but
      does not completely inhibit cell plate formation. Despite such findings, the
      significance and molecular mechanisms of MTs and MFs remain largely unknown.
      RESULTS: Time-sequential changes in MF-distribution were monitored by live
      imaging of tobacco BY-2 cells stably expressing the GFP-actin binding domain 2
      (GFP-ABD2) fusion protein, which vitally co-stained with the endocytic tracer,
      FM4-64, that labels the cell plate. During cytokinesis, MFs accumulated near the
      newly-separated daughter nuclei towards the emerging cell plate, and subsequently
      approached the expanding cell plate edges. Treatment with an actin polymerization
      inhibitor caused a decrease in the cell plate expansion rate, which was
      quantified using time-lapse imaging and regression analysis. Our results
      demonstrated time-sequential changes in the contribution of MFs to cell plate
      expansion; MF-disruption caused about a 10% decrease in the cell plate expansion
      rate at the early phase of cytokinesis, but about 25% at the late phase. MF
      disruption also caused malformation of the emerging cell plate at the early
      phase, indicative of MF involvement in early cell plate formation and expansion.
      The dynamic movement of endosomes around the cell plate was also inhibited by
      treatment with an actin polymerization inhibitor and a myosin ATPase inhibitor,
      respectively. Furthermore, time-lapse imaging of the endoplasmic reticulum (ER)
      revealed that MFs were involved in ER accumulation in the phragmoplast at the
      late phase. CONCLUSION: By expression of GFP-ABD2 and vital staining with FM4-64,
      the dynamics of MFs and the cell plate could be followed throughout plant
      cytokinesis in living cells. Pharmacological treatment and live imaging analysis
      also allowed us to quantify MF contribution to cell plate expansion during
      cytokinesis. Our results suggest that MFs play significant roles in cell plate
      formation and expansion via regulation of endomembrane dynamics.

PMID- 18637165
TI  - Factor structure of the Shoulder Pain and Disability Index in patients with
      adhesive capsulitis.
AB  - BACKGROUND: The Shoulder Pain and Disability Index (SPADI) is a self-administered
      questionnaire that aims to measure pain and disability associated with shoulder
      disease. It consists of a pain section and a disability section with 13 items
      being responded to on visual analogue scales. Few researchers have investigated
      SPADI validity in specified diagnostic groups, although the selection of an
      evaluative instrument should be based on evidence of validity in the target
      patient group. The aim of the present study was to investigate factor structure
      of the SPADI in a study population of patients with adhesive capsulitis. METHODS:
      The questionnaire was administered to 191 patients with adhesive capsulitis.
      Descriptive statistics for items and a comparison of scores for the two subscales
      were produced. Internal consistency was analyzed by use of the Cronbach alpha and
      a principal components analysis with varimax rotation was conducted. Study design
      was cross-sectional. RESULTS: Two factors were extracted, but the factor
      structure failed to support the original division of items into separate pain and
      disability sections. CONCLUSION: We found minimal evidence to justify the use of
      separate subscales for pain and disability. It is our impression that the SPADI
      should be viewed as essentially unidimensional in patients with adhesive
      capsulitis.

PMID- 18637166
TI  - Cardiac lipoma in a patient with a history of malignant tumours: a case report.
AB  - Cardiac tumours are relatively rare. Most of them do not cause clinical symptoms
      so that prior to the introduction of modern methods of investigation they were
      predominately incidental findings during autopsies or open heart surgery.We
      present the case of a 63-year-old German man with a past history of malignant
      melanoma and renal cell carcinoma who presented with a right atrial lipoma and a
      suspicious lesion in the right lower lobe of the lung. Surgical excision of the
      cardiac lipoma was performed and a biopsy of the lung mass was done which
      diagnosed a moderately differentiated adenocarcinoma.

PMID- 18637167
TI  - Selection of housekeeping genes for gene expression studies in the adult rat
      submandibular gland under normal, inflamed, atrophic and regenerative states.
AB  - BACKGROUND: Real-time PCR is a reliable tool with which to measure mRNA
      transcripts, and provides valuable information on gene expression profiles.
      Endogenous controls such as housekeeping genes are used to normalise mRNA levels
      between samples for sensitive comparisons of mRNA transcription. Selection of the
      most stable control gene(s) is therefore critical for the reliable interpretation
      of gene expression data. For the purpose of this study, 7 commonly used
      housekeeping genes were investigated in salivary submandibular glands under
      normal, inflamed, atrophic and regenerative states. RESULTS: The program
      NormFinder identified the suitability of HPRT to use as a single gene for
      normalisation within the normal, inflamed and regenerative states, and GAPDH in
      the atrophic state. For normalisation to multiple housekeeping genes, for each
      individual state, the optimal number of housekeeping genes as given by geNorm
      was: ACTB/UBC in the normal, ACTB/YWHAZ in the inflamed, ACTB/HPRT in the
      atrophic and ACTB/GAPDH in the regenerative state. The most stable housekeeping
      gene identified between states (compared to normal) was UBC. However, ACTB,
      identified as one of the most stably expressed genes within states, was found to
      be one of the most variable between states. Furthermore we demonstrated that
      normalising between states to ACTB, rather than UBC, introduced an approximately
      3 fold magnitude of error. CONCLUSION: Using NormFinder, our studies demonstrated
      the suitability of HPRT to use as a single gene for normalisation within the
      normal, inflamed and regenerative groups and GAPDH in the atrophic group.
      However, if normalising to multiple housekeeping genes, we recommend normalising
      to those identified by geNorm. For normalisation across the physiological states,
      we recommend the use of UBC.

PMID- 18637168
TI  - The impact of individualised cardiovascular disease (CVD) risk estimates and
      lifestyle advice on physical activity in individuals at high risk of CVD: a pilot
      2 x 2 factorial understanding risk trial.
AB  - BACKGROUND: There is currently much interest in encouraging individuals to
      increase physical activity in order to reduce CVD risk. This study has been
      designed to determine if personalised CVD risk appreciation can increase physical
      activity in adults at high risk of CVD. METHODS/DESIGN: In a 2 x 2 factorial
      design participants are allocated at random to a personalised 10-year CVD risk
      estimate or numerical CVD risk factor values (systolic blood pressure, LDL
      cholesterol and fasting glucose) and, simultaneously, to receive a brief
      lifestyle advice intervention targeting physical activity, diet and smoking
      cessation or not. We aim to recruit 200 participants from Oxfordshire primary
      care practices. Eligibility criteria include adults age 40-70 years, estimated 10
      year CVD risk > or =20%, ability to read and write English, no known CVD and no
      physical disability or other condition reducing the ability to walk. Primary
      outcome is physical activity measured by ActiGraph accelerometer with
      biochemical, anthropometrical and psychological measures as additional outcomes.
      Primary analysis is between group physical activity differences at one month
      powered to detect a difference of 30,000 total counts per day of physical
      activity between the groups. Additional analyses will seek to further elucidate
      the relationship between the provision of risk information, and intention to
      change behaviour and to determine the impact of both interventions on clinical
      and anthropometrical measures including fasting and 2 hour plasma glucose,
      fructosamine, serum cotinine, plasma vitamin C, body fat percentage and blood
      pressure. DISCUSSION: This is a pilot trial seeking to demonstrate in a real
      world setting, proof of principal that provision of personalised risk information
      can contribute to behaviour changes aimed at reducing CVD risk. This study will
      increase our understanding of the links between the provision of risk information
      and behaviour change and if successful, could be used in clinical practice with
      little or no modification.

PMID- 18637169
TI  - Portal vein gas in emergency surgery.
AB  - BACKGROUND: Portal vein gas is an ominous radiological sign, which indicates a
      serious gastrointestinal problem in the majority of patients. Many causes have
      been identified and the most important was bowel ischemia and mesenteric vascular
      accident. The presentation of patients is varied and the diagnosis of the
      underlying problem depends mainly on the radiological findings and clinical
      signs. The aim of this article is to show the clinical importance of portal vein
      gas and its management in emergency surgery. METHODS: A computerised search was
      made of the Medline for publications discussing portal vein gas through March
      2008. Sixty articles were identified and selected for this review because of
      their relevance. These articles cover a period from 1975-2008. RESULTS: Two
      hundreds and seventy-five patients with gas in the portal venous system were
      reported. The commonest cause for portal vein gas was bowel ischemia and
      mesenteric vascular pathology (61.44%). This was followed by inflammation of the
      gastrointestinal tract (16.26%), obstruction and dilatation (9.03%), sepsis
      (6.6%), iatrogenic injury and trauma (3.01%) and cancer (1.8%). Idiopathic portal
      vein gas was also reported (1.8%). CONCLUSION: Portal vein gas is a diagnostic
      sign, which indicates a serious intra-abdominal pathology requiring emergency
      surgery in the majority of patients. Portal vein gas due to simple and benign
      cause can be treated conservatively. Correlation between clinical and diagnostic
      findings is important to set the management plan.

PMID- 18637170
TI  - Another challenge for scientists.
AB  - By nature, scientists contribute to our understanding of nature and ourselves. As
      communities undergo significant changes, new challenges are presented. Here, we
      offer alternative views on recent changes in society.

PMID- 18637171
TI  - A stitch in time: efficient computation of genomic DNA melting bubbles.
AB  - BACKGROUND: It is of biological interest to make genome-wide predictions of the
      locations of DNA melting bubbles using statistical mechanics models.
      Computationally, this poses the challenge that a generic search through all
      combinations of bubble starts and ends is quadratic. RESULTS: An efficient
      algorithm is described, which shows that the time complexity of the task is
      O(NlogN) rather than quadratic. The algorithm exploits that bubble lengths may be
      limited, but without a prior assumption of a maximal bubble length. No
      approximations, such as windowing, have been introduced to reduce the time
      complexity. More than just finding the bubbles, the algorithm produces a stitch
      profile, which is a probabilistic graphical model of bubbles and helical regions.
      The algorithm applies a probability peak finding method based on a hierarchical
      analysis of the energy barriers in the Poland-Scheraga model. CONCLUSION: Exact
      and fast computation of genomic stitch profiles is thus feasible. Sequences of
      several megabases have been computed, only limited by computer memory. Possible
      applications are the genome-wide comparisons of bubbles with promotors, TSS,
      viral integration sites, and other melting-related regions.

PMID- 18637172
TI  - Incidence of human brucellosis in a rural area in Western Greece after the
      implementation of a vaccination programme against animal brucellosis.
AB  - BACKGROUND: Brucellosis continues to be an important source of morbidity in
      several countries, particularly among agricultural and pastoral populations. The
      purpose of this study was to examine if there is an effect on the incidence of
      human brucellosis after the implementation of an animal brucellosis control
      programme. METHODS: The study was conducted in the Municipality of Tritaia in the
      Prefecture of Achaia in Western Greece during the periods 1997-1998 and 2000
      2002. Health education efforts were made during 1997-1998 to make the public take
      preventive measures. In the time period from January 1999 to August 2002 a
      vaccination programme against animal brucellosis was realised in the specific
      region. The vaccine used was the B. melitensis Rev-1 administered by the
      conjuctival route. Comparisons were performed between the incidence rates of the
      two studied periods. RESULTS: There was a great fall in the incidence rate
      between 1997-1998 (10.3 per 1,000 population) and the period 2000-2002 after the
      vaccination (0.3 per 1,000 population). The considerable decrease of the human
      incidence rate is also observed in the period 2000-2002 among persons whose herds
      were not as yet vaccinated (1.4 vs. 10.3 per 1,000 population), indicating a
      possible role of health education in the decline of human brucellosis.
      CONCLUSION: The study reveals a statistically significant decline in the
      incidence of human brucellosis after the vaccination programme and underlines the
      importance of an ongoing control of animal brucellosis in the prevention of human
      brucellosis. The reduction of human brucellosis can be best achieved by a
      combination of health education and mass animal vaccination.

PMID- 18637173
TI  - Topology of evolving, mutagenized viral populations: quasispecies expansion,
      compression, and operation of negative selection.
AB  - BACKGROUND: The molecular events and evolutionary forces underlying lethal
      mutagenesis of virus (or virus extinction through an excess of mutations) are not
      well understood. Here we apply for the first time phylogenetic methods and
      Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra
      population structures of mutant spectra of foot-and-mouth disease virus (FMDV)
      quasispecies subjected to mutagenesis by base and nucleoside analogues. RESULTS:
      Phylogenetic and PAQ analyses have revealed a highly dynamic variation of
      intrapopulation diversity of FMDV quasispecies. The population diversity first
      suffers striking expansions in the presence of mutagens and then compressions
      either when the presence of the mutagenic analogue was discontinued or when a
      mutation that decreased sensitivity to a mutagen was selected. The pattern of
      mutations found in the populations was in agreement with the behavior of the
      corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at
      preferred genomic sites, and dn/ds ratios indicate the operation of negative (or
      purifying) selection in populations subjected to mutagenesis. No evidence of
      unusually elevated genetic distances has been obtained for FMDV populations
      approaching extinction. CONCLUSION: Phylogenetic and PAQ analysis provide
      adequate procedures to describe the evolution of viral sequences subjected to
      lethal mutagenesis. These methods define the changes of intra-population
      structure more precisely than mutation frequencies and Shannon entropies. PAQ is
      very sensitive to variations of intrapopulation genetic distances. Strong
      negative (or purifying) selection operates in FMDV populations subjected to
      enhanced mutagenesis. The quantifications provide evidence that extinction does
      not imply unusual increases of intrapopulation complexity, in support of the
      lethal defection model of virus extinction.

PMID- 18637174
TI  - MSDmotif: exploring protein sites and motifs.
AB  - BACKGROUND: Protein structures have conserved features - motifs, which have a
      sufficient influence on the protein function. These motifs can be found in
      sequence as well as in 3D space. Understanding of these fragments is essential
      for 3D structure prediction, modelling and drug-design. The Protein Data Bank
      (PDB) is the source of this information however present search tools have limited
      3D options to integrate protein sequence with its 3D structure. RESULTS: We
      describe here a web application for querying the PDB for ligands, binding sites,
      small 3D structural and sequence motifs and the underlying database. Novel
      algorithms for chemical fragments, 3D motifs, phi/psi sequences, super-secondary
      structure motifs and for small 3D structural motif associations searches are
      incorporated. The interface provides functionality for visualization, search
      criteria creation, sequence and 3D multiple alignment options. MSDmotif is an
      integrated system where a results page is also a search form. A set of motif
      statistics is available for analysis. This set includes molecule and motif
      binding statistics, distribution of motif sequences, occurrence of an amino-acid
      within a motif, correlation of amino-acids side-chain charges within a motif and
      Ramachandran plots for each residue. The binding statistics are presented in
      association with properties that include a ligand fragment library. Access is
      also provided through the distributed Annotation System (DAS) protocol. An
      additional entry point facilitates XML requests with XML responses. CONCLUSION:
      MSDmotif is unique by combining chemical, sequence and 3D data in a single search
      engine with a range of search and visualisation options. It provides multiple
      views of data found in the PDB archive for exploring protein structures.

PMID- 18637175
TI  - PRFdb: a database of computationally predicted eukaryotic programmed -1 ribosomal
      frameshift signals.
AB  - BACKGROUND: The Programmed Ribosomal Frameshift Database (PRFdb) provides an
      interface to help researchers identify potential programmed -1 ribosomal
      frameshift (-1 PRF) signals in eukaryotic genes or sequences of interest.
      RESULTS: To identify putative -1 PRF signals, sequences are first imported from
      whole genomes or datasets, e.g. the yeast genome project and mammalian gene
      collection. They are then filtered through multiple algorithms to identify
      potential -1 PRF signals as defined by a heptameric slippery site followed by an
      mRNA pseudoknot. The significance of each candidate -1 PRF signal is evaluated by
      comparing the predicted thermodynamic stability (DeltaG degrees ) of the native
      mRNA sequence against a distribution of DeltaG degrees values of a pool of
      randomized sequences derived from the original. The data have been compiled in a
      user-friendly, easily searchable relational database. CONCLUSION: The PRFdB
      enables members of the research community to determine whether genes that they
      are investigating contain potential -1 PRF signals, and can be used as a
      metasource of information for cross referencing with other databases. It is
      available on the web at http://dinmanlab.umd.edu/prfdb.

PMID- 18637176
TI  - Perceptions about the cause of schizophrenia and the subsequent help seeking
      behavior in a Pakistani population - results of a cross-sectional survey.
AB  - BACKGROUND: There is a cultural variability around the perception of what causes
      the syndrome of schizophrenia. Generally patients with schizophrenia are
      considered dangerous. They are isolated and treatment is delayed. Studies have
      shown favorable prognosis with good family and social support, early diagnosis
      and management. Duration of untreated psychosis is a bad prognostic indicator. We
      aimed to determine the perceptions regarding the etiology of schizophrenia and
      the subsequent help seeking behavior. METHODS: This cross-sectional study was
      carried out on a sample of 404 people at the out patient departments of Aga Khan
      University Hospital Karachi. Data was collected via a self-administered
      questionnaire. Questions were related to a vignette of a young man displaying
      schizophrenic behavior. Data was analyzed on SPSS v 14. RESULTS: The mean age of
      the participants was 31.4 years (range = 18-72) and 77% of them were males. The
      majorities were graduates (61.9%) and employed (50%). Only 30% of the
      participants attributed 'mental illness' as the main cause of psychotic symptoms
      while a large number thought of 'God's will' (32.3%), 'superstitious ideas'
      (33.1%), 'loneliness' (24.8%) and 'unemployment' (19.3%) as the main cause.
      Mental illness as the single most important cause was reported by only 22%. As
      far as management is concerned, only 40% reported psychiatric consultation to be
      the single most important management step. Other responses included spiritual
      healing (19.5%) and Sociachanges (10.6) while 14.8% of respondents said that they
      would do nothing. Gender, age, family system and education level were
      significantly associated with the beliefs about the cause of schizophrenia (p <
      0.05). While these variables plus 'religious inclination' and 'beliefs about
      cause' were significantly associated with the help seeking behavior of the
      participants. CONCLUSION: Despite majority of the study population being well
      educated, only a few recognized schizophrenia as a mental illness and many held
      superstitious beliefs. A vast majority of Pakistanis have non-biomedical beliefs
      about the cause of schizophrenia. Their help seeking behavior in this regard is
      inappropriate and detrimental to the health of schizophrenic patients. Areas for
      future research have been identified.

PMID- 18637177
TI  - Integrated modeling and experimental approach for determining transcription
      factor profiles from fluorescent reporter data.
AB  - BACKGROUND: The development of quantitative models of signal transduction, as
      well as parameter estimation to improve existing models, depends on the ability
      to obtain quantitative information about various proteins that are part of the
      signaling pathway. However, commonly-used measurement techniques such as Western
      blots and mobility shift assays provide only qualitative or semi-quantitative
      data which cannot be used for estimating parameters. Thus there is a clear need
      for techniques that enable quantitative determination of signal transduction
      intermediates. RESULTS: This paper presents an integrated modeling and
      experimental approach for quantitatively determining transcription factor
      profiles from green fluorescent protein (GFP) reporter data. The technique
      consists of three steps: (1) creating data sets for green fluorescent reporter
      systems upon stimulation, (2) analyzing the fluorescence images to determine
      fluorescence intensity profiles using principal component analysis (PCA) and K
      means clustering, and (3) computing the transcription factor concentration from
      the fluorescence intensity profiles by inverting a model describing
      transcription, translation, and activation of green fluorescent proteins. We have
      used this technique to quantitatively characterize activation of the
      transcription factor NF-kappaB by the cytokine TNF-alpha. In addition, we have
      applied the quantitative NF-kappaB profiles obtained from our technique to
      develop a model for TNF-alpha signal transduction where the parameters were
      estimated from the obtained data. CONCLUSION: The technique presented here for
      computing transcription factor profiles from fluorescence microscopy images of
      reporter cells generated quantitative data on the magnitude and dynamics of NF
      kappaB activation by TNF-alpha. The obtained results are in good agreement with
      qualitative descriptions of NF-kappaB activation as well as semi-quantitative
      experimental data from the literature. The profiles computed from the
      experimental data have been used to re-estimate parameters for a NF-kappaB model
      and the results of additional experiments are predicted very well by the model
      with the new parameter values. While the presented approach has been applied to
      NF-kappaB and TNF-alpha signaling, it can be used to determine the profile of any
      transcription factor as long as GFP reporter fluorescent profiles are available.

PMID- 18637178
TI  - Experiences of abortion: a narrative review of qualitative studies.
AB  - BACKGROUND: Although abortion or termination of pregnancy (TOP) has become an
      increasingly normalized component of women's health care over the past forty
      years, insufficient attention has been paid to women's experiences of surgical or
      medical methods of TOP. OBJECTIVE: To undertake a narrative review of qualitative
      studies of women's experiences of TOP and their perspectives on surgical or
      medical methods. METHODS: Keyword searches of Medline, CINAHL, ISI, and IBSS
      databases. Manual searches of other relevant journals and reference lists of
      primary articles. RESULTS: Qualitative studies (n = 18) on women's experiences of
      abortion were identified. Analysis of the results of studies reviewed revealed
      three main themes: experiential factors that promote or inhibit the choice to
      seek TOP; experiences of TOP; and experiential aspects of the environment in
      which TOP takes place. CONCLUSION: Women's choices about TOP are mainly pragmatic
      ones that are related to negotiating finite personal and family and emotional
      resources. Women who are well informed and supported in their choices experience
      good psychosocial outcomes from TOP. Home TOP using mifepristone appears
      attractive to women who are concerned about professionals' negative attitudes and
      lack of privacy in formal healthcare settings but also leads to concerns about
      management and safety.

PMID- 18637179
TI  - Intrathoracic migration of ventriculoperitoneal shunt: a case report.
AB  - INTRODUCTION: Intrathoracic migration of ventriculoperitoneal shunt can be
      transdiaphragmatic or supradiaphragmatic. This complication causes important
      respiratory symptoms. CASE PRESENTATION: A 7 year-old Caucasian female,
      hospitalized with the prediagnosis of pneumonia, was determined to have
      ventriculoperitoneal shunt migration at left hemithorax. A left thoracotomy was
      performed and the shunt was successfully removed transdiaphragmatically.
      CONCLUSION: The patients with intrathoracic migration of ventriculoperitoneal
      shunt must be treated surgically as soon as possible. Transdiaphragmatic surgical
      approach would be more suitable from the point of surgical easiness.

PMID- 18637180
TI  - Desflurane Consumption During Automated Closed-circuit Delivery is Higher Than
      When a Conventional Anesthesia Machine is Used With a Simple Vaporizer-O2-N2O
      Fresh Gas Flow Sequence.
AB  - BACKGROUND: The Zeus(r) (Drager, Lubeck, Germany), an automated closed-circuit
      anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and
      the lungs, and intermittently flushes the system to remove unwanted N2. We
      hypothesized this could increase desflurane consumption to such an extent that
      agent consumption might become higher than with a conventional anesthesia machine
      (Anesthesia Delivery Unit [ADU(r)], GE, Helsinki, Finland) used with a previously
      derived desflurane-O2-N2O administration schedule that allows early FGF
      reduction. METHODS: Thirty-four ASA PS I or II patients undergoing plastic,
      urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group
      (n = 24), an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively)
      was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer
      setting (FD) was 6.5% for the first 15 min, and 5.5% during the next 25 min. In
      the Zeus group (n = 10), the Zeus(r) was used in automated closed circuit
      anesthesia mode with a selected end-expired (FA) desflurane target of 4.6%, and
      O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and
      consumption during the first 40 min were compared using repeated measures one-way
      ANOVA. RESULTS: Age and weight did not differ between the groups (P > 0.05), but
      patients in the Zeus group were taller (P = 0.04). In the Zeus group, the
      desflurane FA was lower during the first 3 min (P < 0.05), identical at 4 min (P
      > 0.05), and slightly higher after 4 min (P < 0.05). Desflurane consumption was
      higher in the Zeus group at all times, a difference that persisted after
      correcting for the small difference in FA between the two groups. CONCLUSION:
      Agent consumption with an automated closed-circuit anesthesia machine is higher
      than with a conventional anesthesia machine when the latter is used with a
      specific vaporizer-FGF sequence. Agent consumption during automated delivery
      might be further reduced by optimizing the algorithm(s) that manages the initial
      FGF or by tolerating some N2 in the circuit to minimize the need for intermittent
      flushing.

PMID- 18637181
TI  - Long catheter sign: a reliable bedside sign of incorrect positioning of foley
      catheter in male spinal cord injury patients.
AB  - INTRODUCTION: Indwelling urethral catheter is often used in male spinal cord
      injury patients to provide drainage to neuropathic bladder. If the balloon of a
      Foley catheter is inflated in urethra or, when a properly inserted Foley catheter
      is later pulled and thereby, the Foley balloon comes to lie in urethra, an
      excessive length of catheter will remain outside the penis. This sign is termed
      "long catheter sign". Long catheter sign will also be positive when Foley
      catheter slips out of urinary bladder in situations where Foley balloon is
      ruptured by a spiky vesical calculus or deflated due to a defective valve. CASE
      PRESENTATION: A fifty-year-old Caucasian male with paraplegia at T-5 level had
      been managing neuropathic bladder by long-term indwelling urethral catheter.
      During his stay in spinal unit, the patient felt that there had been a tug on the
      drainage tube when he was being turned during night as part of the routine care
      for relief of pressure. Next morning, a health professional noticed that a long
      segment of catheter was lying outside penis. There was no bleeding from urethral
      meatus. Catheter continued to drain urine, which was yellowish in colour. Urine
      output was satisfactory. This patient did not develop any clinical feature of
      autonomic dysreflexia nor was he feeling unwell. In view of positive long
      catheter sign, radiological studies were performed to check the position of Foley
      catheter, which confirmed the clinical impression of incorrectly positioned Foley
      catheter. The catheter was removed; flexible cystoscopy was performed. A 16 Fr,
      20 ml balloon Foley catheter was inserted over a 0.032" guide wire. Following
      this procedure, a considerably shorter length of Foley catheter remained outside
      the penis. CONCLUSION: Positive long catheter sign indicates that the Foley
      catheter is placed incorrectly and needs repositioning urgently. Prompt
      recognition of long catheter sign and immediate repositioning of Foley catheter
      will help to prevent complications such as chronic distension of urinary bladder,
      urine infection, and pressure necrosis of urethra especially if Foley balloon
      remains inflated within urethra for a long period. In this patient, use of a
      Foley catheter with 20 ml balloon, and securing the drainage tube to thigh with
      two straps, helped to prevent inadvertent pull of Foley balloon into the urethra.

PMID- 18637182
TI  - Lack of basic and luxury goods and health-related dysfunction in older persons;
      findings from the longitudinal SMILE study.
AB  - BACKGROUND: More so than the traditional socioeconomic indicators, such as
      education and income, wealth reflects the accumulation of resources and makes
      socioeconomic ranking manifest and explicitly visible to the outside world. While
      the lack of basic goods, such as a refrigerator, may affect health directly, via
      biological pathways, the lack of luxury goods, such as an LCD television, may
      affect health indirectly through psychosocial mechanisms. We set out to examine,
      firstly, the relevance of both basic and luxury goods in explaining health
      related dysfunction in older persons, and, secondly, the extent to which these
      associations are independent of traditional socioeconomic indicators. METHODS:
      Cross-sectional and longitudinal data from 2067 men and women aged 55 years and
      older who participated in the Study on Medical Information and Lifestyles
      Eindhoven (SMILE) were gathered. Logistic regression analyses were used to study
      the relation between a lack of basic and luxury goods and health-related
      function, assessed with two sub-domains of the SF-36. RESULTS: The lack of basic
      goods was closely related to incident physical (OR = 2.32) and mental (OR = 2.12)
      dysfunction, even when the traditional measures of socioeconomic status, i.e.
      education or income, were taken into account. Cross-sectional analyses, in which
      basic and luxury goods were compared, showed that the lack of basic goods was
      strongly associated with mental dysfunction. Lack of luxury goods was, however,
      not related to dysfunction. CONCLUSION: Even in a relatively wealthy country like
      the Netherlands, the lack of certain basic goods is not uncommon. More
      importantly, lack of basic goods, as an indicator of wealth, was strongly related
      to health-related dysfunction also when traditional measures of socioeconomic
      status were taken into account. In contrast, no effects of luxury goods on
      physical or mental dysfunction were found. Future longitudinal research is
      necessary to clarify the precise mechanisms underlying these effects.

PMID- 18637183
TI  - Fractal parameters and vascular networks: facts & artifacts.
AB  - BACKGROUND: Several fractal and non-fractal parameters have been considered for
      the quantitative assessment of the vascular architecture, using a variety of test
      specimens and of computational tools. The fractal parameters have the advantage
      of being scale invariant, i.e. to be independent of the magnification and
      resolution of the images to be investigated, making easier the comparison among
      different setups and experiments. RESULTS: The success of several commercial
      and/or free codes in computing the fractal parameters has been tested on well
      known exact models. Based on such a preliminary study, we selected the code Frac
      lac in order to analyze images obtained by visualizing the angiogenetic process
      occurring in chick Chorio Allontoic Membranes (CAM), assumed to be paradigmatic
      of a realistic 2D vascular network. Among the parameters investigated, the
      fractal dimension Df proved to be the most robust estimator for CAM vascular
      networks. Moreover, only Df was able to discriminate between effective and
      elusive increases in vascularization after drug-induced angiogenic stimulations
      on CAMs. CONCLUSION: The fractal dimension Df is likely to be the most promising
      tool for monitoring the effectiveness of anti-angiogenic therapies in various
      clinical contexts.

PMID- 18637184
TI  - Implications of tyrosine phosphoproteomics in cervical carcinogenesis.
AB  - BACKGROUND: Worldwide cervical cancer remains a leading cause of mortality from
      gynecologic malignancies. The link between cervical cancer and persistent
      infection with HPV has been established. At a molecular level little is known
      about the transition from the precancerous state to invasive cancer. To elucidate
      this process, cervical biopsies from human specimens were obtained from
      precancerous state to stage III disease. METHODS: Cervical biopsies were obtained
      from patients with a diagnosis of cervical cancer undergoing definitive surgery
      or staging operation. Biopsies were obtained from patients with precancerous
      lesions at the time of their excisional procedure. Control samples were obtained
      from patients undergoing hysterectomy for benign conditions such as fibroids.
      Samples were subjected to proteomic profiling using two dimensional gel
      electrophoresis with subsequent trypsin digestion followed by MALDI-TOF protein
      identification. Candidate proteins were then further studied using western
      blotting, immunoprecipitation and immunohistochemistry. RESULTS: Annexin A1 and
      DNA-PKcs were found to be differentially expressed. Phosphorylated annexin A1 was
      up regulated in diseased states in comparison to control and its level was
      strongly detected in the serum of cervical cancer patients compared to controls.
      DNA-PKcs was noted to be hyperphosphorylated and fragmented in cancer when
      compared to controls. By immunohistochemistry annexin A1 was noted in the
      vascular environment in cancer and certain precancerous samples. CONCLUSION: This
      study suggests a probable role for protein tyrosine phosphorylation in cervical
      carcinogenesis. Annexin A1 and DNA-PK cs may have synergistic effects with HPV
      infection. Precancerous lesions that may progress to cervical cancer may be
      differentiated from lesions that will not base on similar immunohistochemical
      profile to invasive squamous cell carcinoma.

PMID- 18637185
TI  - Potential antiproteolytic effects of L-leucine: observations of in vitro and in
      vivo studies.
AB  - The purpose of present review is to describe the effect of leucine
      supplementation on skeletal muscle proteolysis suppression in both in vivo and in
      vitro studies. Most studies, using in vitro methodology, incubated skeletal
      muscles with leucine with different doses and the results suggests that there is
      a dose-dependent effect. The same responses can be observed in in vivo studies.
      Importantly, the leucine effects on skeletal muscle protein synthesis are not
      always connected to the inhibition of skeletal muscle proteolysis. As a matter of
      fact, high doses of leucine incubation can promote suppression of muscle
      proteolysis without additional effects on protein synthesis, and low leucine
      doses improve skeletal muscle protein ynthesis but have no effect on skeletal
      muscle proteolysis. These research findings may have an important clinical
      relevancy, because muscle loss in atrophic states would be reversed by specific
      leucine supplementation doses. Additionally, it has been clearly demonstrated
      that leucine administration suppresses skeletal muscle proteolysis in various
      catabolic states. Thus, if protein metabolism changes during different atrophic
      conditions, it is not surprising that the leucine dose-effect relationship must
      also change, according to atrophy or pathological state and catabolism magnitude.
      In conclusion, leucine has a potential role on attenuate skeletal muscle
      proteolysis. Future studies will help to sharpen the leucine efficacy on skeletal
      muscle protein degradation during several atrophic states.

PMID- 18637186
TI  - Regulation of primate lentiviral RNA dimerization by structural entrapment.
AB  - BACKGROUND: Genomic RNA dimerization is an important process in the formation of
      an infectious lentiviral particle. One of the signals involved is the stem-loop 1
      (SL1) element located in the leader region of lentiviral genomic RNAs which also
      plays a role in encapsidation and reverse transcription. Recent studies revealed
      that HIV types 1 and 2 leader RNAs adopt different conformations that influence
      the presentation of RNA signals such as SL1. To determine whether common
      mechanisms of SL1 regulation exist among divergent lentiviral leader RNAs, here
      we compare the dimerization properties of SIVmac239, HIV-1, and HIV-2 leader RNA
      fragments using homologous constructs and experimental conditions. Prior studies
      from several groups have employed a variety of constructs and experimental
      conditions. RESULTS: Although some idiosyncratic differences in the dimerization
      details were observed, we find unifying principles in the regulation strategies
      of the three viral RNAs through long- and short-range base pairing interactions.
      Presentation and efficacy of dimerization through SL1 depends strongly upon the
      formation or dissolution of the lower stem of SL1 called stem B. SL1 usage may
      also be down-regulated by long-range interactions involving sequences between SL1
      and the first codons of the gag gene. CONCLUSION: Despite their sequence
      differences, all three lentiviral RNAs tested in this study showed a local
      regulation of dimerization through the stabilization of SL1.

PMID- 18637187
TI  - Fatal injection of ranitidine: a case report.
AB  - INTRODUCTION: Ranitidine hydrochloride (Zantac), a histamine-2-receptor
      antagonist, is a widely used medication with an excellent safety record.
      Anaphylactic reaction to ranitidine is an extremely rare event and a related
      death has never been described in the literature. CASE PRESENTATION: We present
      the clinical history, histological and toxicological data of a 51-year-old man
      with negative anamnesis for allergic events, who died suddenly after the
      intravenous administration of one phial of Zantac 50 mg prescribed as a routine
      post-surgical prophylaxis for stress ulcer. CONCLUSION: Although the incidence of
      anaphylactic reactions related to ranitidine is low, caution needs to be
      exercised on administration of this drug. In addition, further study is needed to
      define strategies for the prevention of adverse drug reactions in hospitalized
      patients.

PMID- 18637188
TI  - RAS gene polymorphisms, classical risk factors and the advent of coronary artery
      disease in the Portuguese population.
AB  - BACKGROUND: Several polymorphisms within the renin-angiotensin system cluster of
      genes have been associated with the advent of coronary artery disease (CAD) or
      related pathologies. We investigated the distribution of 5 of these polymorphisms
      in order to find any association with CAD development and distinguish if any of
      the biochemical and behavioural factors interact with genetic polymorphisms in
      the advent of the disease. METHODS: ACE I/D (rs4340), ACE A11860G (rs4343), AT1R
      A1166C (rs5186), AGT T174M (rs4762) and AGT M235T (rs699) gene polymorphisms were
      PCR-RFLP analysed in 298 CAD patients and 510 controls from Portugal. Several
      biochemical and behavioural markers were obtained. RESULTS: ACE I/D DD and
      ACE11860 GG genotypes are risk factors for CAD in this population. The
      simultaneous presence of ACE I/D I and ACE11860 A alleles corresponds to a
      significant trend towards a decrease in CAD incidence. We found several
      synergistic effects between the studied polymorphisms and classical risk factors
      such as hypertension, obesity, diabetes and dyslipidaemia: the presence of the DD
      genotype of ACE I/D (and also ACE11860 GG) increases the odds of developing CAD
      when associated to each one of these classical risk factors, particularly when
      considering the male and early onset CAD subgroup analysis; AGT235 TT also
      increases the CAD risk in the presence of hypertension and dyslipidaemia, and
      AT1R1166 interacts positively with hypertension, smoking and obesity. CONCLUSION:
      ACE polymorphisms were shown to play a major role in individual susceptibility to
      develop CAD. There is also a clear interaction between RAS predisposing genes and
      some biochemical/environmental risk factors in CAD onset, demonstrating a
      significant enhancement of classical markers particularly by ACE I/D and
      ACE11860.

PMID- 18637189
TI  - Clinical evidence continuous medical education: a randomised educational trial of
      an open access e-learning program for transferring evidence-based information -
      ICEKUBE (Italian Clinical Evidence Knowledge Utilization Behaviour Evaluation) -
      study protocol.
AB  - BACKGROUND: In an effort to ensure that all physicians have access to valid and
      reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free
      access e-learning system, based on Clinical Evidence, called ECCE. Doctors have
      access to an electronic version and related clinical vignettes. Correct answers
      to the interactive vignettes provide Continuing Medical Education credits. The
      aims of this trial are to establish whether the e-learning program (ECCE)
      increases physicians' basic knowledge about common clinical scenarios, and
      whether ECCE is superior to the passive diffusion of information through the
      printed version of Clinical Evidence. DESIGN: All Italian doctors naive to ECCE
      will be randomised to three groups. Group one will have access to ECCE for
      Clinical Evidence chapters and vignettes lot A and will provide control data for
      Clinical Evidence chapters and vignettes lot B; group two vice versa; group three
      will receive the concise printed version of Clinical Evidence. There are in fact
      two designs: a before and after pragmatic trial utilising a two by two incomplete
      block design (group one versus group two) and a classical design (group one and
      two versus group three). The primary outcome will be the retention of Clinical
      Evidence contents assessed from the scores for clinical vignettes selected from
      ECCE at least six months after the intervention. To avoid test-retest effects, we
      will randomly select vignettes out of lot A and lot B, avoiding repetitions. In
      order to preserve the comparability of lots, we will select vignettes with
      similar, optimal psychometric characteristics.

PMID- 18637190
TI  - Brain-derived neurotrophic factor and its receptor in the human and the sand rat
      intervertebral disc.
AB  - INTRODUCTION: Brain-derived neurotrophic factor (BDNF) was first identified in
      the intervertebral disc (IVD) when its molecular upregulation was observed in
      sections of nucleus pulposus cultured under conditions of increased osmolarity.
      BDNF is now known to be involved in a number of biologic functions, including
      regulation of differentiation/survival of sensory neurons, regulation of
      nociceptive function and central pain modulation, and modulation of inflammatory
      pain hypersensitivity. In addition, more recent investigations show that BDNF can
      induce the recruitment of endothelial cells and the formation of vascular
      structures. The objectives of the present study were to use immunocytochemistry
      to determine the distribution of BDNF and its receptor (BDNF-tropomyosine
      receptor kinase B) in the human IVD, and to test for gene expression of BDNF and
      its receptor in cultured human annulus fibrosus cells. METHODS: We studied
      immunohistochemical localization of BDNF and its receptor in the human annulus,
      quantified the percentage of outer annulus and inner annulus cells and nucleus
      cells positive for BDNF immunolocalization, and studied the gene expression of
      BDNF and its receptor using microarray analysis. RESULTS: The percentage (mean +/
      standard error of the mean) of cells positive for BDNF localization was
      significantly greater in the outer annulus (32.3 +/- 2.7%, n = 22) compared with
      either the inner annulus (8.1 +/- 1.5%, n = 6) or the nucleus (10.4 +/- 2.8%, n =
      3) (P < 0.0001). BDNF-receptor immunolocalization showed a pattern similar to
      that of BDNF, but was not quantitatively assessed. BDNF gene expression levels
      from cultured annulus cells showed a significant positive correlation with
      increasing levels of IVD degeneration (P = 0.011). CONCLUSION: These findings
      provide data on the presence of BDNF and its receptor in the human IVD at the
      translational level, and on the expression of BDNF and its receptor by cultured
      human annulus cells. Our findings point to the need for further studies to define
      the role of BDNF in the human IVD and to investigate regulatory events within the
      disc that control the expression of BDNF and its receptor.

PMID- 18637191
TI  - Rationale, design and methodology for a Prospective Randomized Study of graft
      patency in Off-pump and On-pump MultI-vessel coronary artery bypasS Surgery
      (PROMISS) using multidetector computed tomography.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting has been accused of possibly
      compromising graft patency. Sixteen slice computed tomography has shown good
      diagnostic accuracy in the assessment of coronary bypass graft patency when
      compared with conventional coronary artery angiography and is less invasive. The
      study hypothesis is that coronary artery bypass grafting (CABG) performed without
      cardiopulmonary bypass (Off-Pump) has equivalent early graft patency as if
      performed with cardiopulmonary bypass (On-Pump) and may have reduced complication
      rate. METHODS/DESIGN: The Prospective Randomized Comparison of Off-Pump and On
      Pump MultI-vessel Coronary Artery BypasS Surgery (PROMISS) is a controlled,
      single blinded, single centre clinical trial, comparing early graft patency using
      16-slice computed tomography in patients with multi-vessel coronary artery
      disease operated either without or with extracorporeal circulation. Inclusion
      criteria are multivessel disease with an indication for first time, isolated, non
      emergent coronary artery bypass grafting with a minimum of three distal
      anastomoses. Secondary end points are peri-operative mortality, combined
      morbidity, length of stay, neuro-cognitive testing at 6 weeks and adverse events,
      stress test and quality of life at 6 months and one year. The sample size of one
      hundred and fifty patients was calculated in order to enable the detection of a
      5% difference in graft patency, with 80% power, considering a minimum of 3 distal
      anastomoses per patient. Enrollment started in April 2005 and ended July 2007
      with study closure in July 2008. CONCLUSION: The PROMISS trial aims to shed new
      light on the effect of Off-Pump as compared to On-Pump coronary artery bypass
      surgery on graft patency, assessed by multidetector computed tomography, in
      unselected patients with multivessel coronary artery disease. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN58800729.

PMID- 18637192
TI  - Clinically relevant safety issues associated with St. John's wort product labels.
AB  - BACKGROUND: St. John's wort (SJW), used to treat depression, is popular in the
      USA, Canada, and parts of Europe. However, there are documented interactions
      between SJW and prescription medications including warfarin, cyclosporine,
      indinavir, and oral contraceptives. One source of information about these safety
      considerations is the product label. The aim of this study was to evaluate the
      clinically relevant safety information included on labeling in a nationally
      representative sample of SJW products from the USA. METHODS: Eight clinically
      relevant safety issues were identified: drug interactions (SJW-HIV medications,
      SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin),
      contraindications (bipolar disorder), therapeutic duplication (antidepressants),
      and general considerations (phototoxicity and advice to consult a healthcare
      professional (HCP)). A list of SJW products was identified to assess their
      labels. Percentages and totals were used to present findings. RESULTS: Of the
      seventy-four products evaluated, no product label provided information for all 8
      evaluation criteria. Three products (4.1%) provided information on 7 of the 8
      criteria. Four products provided no safety information whatsoever. Percentage of
      products with label information was: SJW-HIV (8.1%), SJW-immunosupressants
      (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants
      (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related
      information on labels included warnings about pregnancy (74.3%), lactation
      (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients
      under 18 years old (13.5%). The average number of a priori safety issues included
      on a product label was 1.91 (range 0-8) for 23.9% completeness. CONCLUSION: The
      vast majority of SJW products fail to adequately address clinically relevant
      safety issues on their labeling. A few products do provide an acceptable amount
      of information on clinically relevant safety issues which could enhance the
      quality of counseling by HCPs and health store clerks. HCPs and consumers may
      benefit if the FDA re-examined labeling requirements for dietary supplements.

PMID- 18637193
TI  - Comparative transcriptomics of human multipotent stem cells during adipogenesis
      and osteoblastogenesis.
AB  - BACKGROUND: A reciprocal relationship between bone and fat development in
      osteoporosis is clinically well established. Some of the key molecular regulators
      involved in this tissue replacement process have been identified. The detailed
      mechanisms governing the differentiation of mesenchymal stem cells (MSC) - the
      key cells involved - are however only now beginning to emerge. In an attempt to
      address the regulation of the adipocyte/osteoblast balance at the level of gene
      transcription in a comprehensive and unbiased manner, we performed a large-scale
      gene expression profiling study using a unique cellular model, human multipotent
      adipose tissue-derived stem cells (hMADS). RESULTS: The analysis of 1606 genes
      that were found to be differentially expressed between adipogenesis and
      osteoblastogenesis revealed gene repression to be most prevalent prior to
      commitment in both lineages. Computational analyses suggested that this gene
      repression is mediated by miRNAs. The transcriptional activation of lineage
      specific molecular processes in both cases occurred predominantly after
      commitment. Analyses of the gene expression data and promoter sequences produced
      a set of 65 genes that are candidates for genes involved in the process of
      adipocyte/osteoblast commitment. Four of these genes were studied in more detail:
      LXRalpha and phospholipid transfer protein (PLTP) for adipogenesis, the nuclear
      receptor COUP-TF1 and one uncharacterized gene, TMEM135 for osteoblastogenesis.
      PLTP was secreted during both early and late time points of hMADS adipocyte
      differentiation. LXRalpha, COUP-TF1, and the transmembrane protein TMEM135 were
      studied in primary cultures of differentiating bone marrow stromal cells from
      healthy donors and were found to be transcriptionally activated in the
      corresponding lineages. CONCLUSION: Our results reveal gene repression as a
      predominant early mechanism before final cell commitment. We were moreover able
      to identify 65 genes as candidates for genes controlling the adipocyte/osteoblast
      balance and to further evaluate four of these. Additional studies will explore
      the precise role of these candidate genes in regulating the
      adipogenesis/osteoblastogenesis switch.

PMID- 18637194
TI  - Oral keratinocytes support non-replicative infection and transfer of harbored HIV
      1 to permissive cells.
AB  - BACKGROUND: Oral keratinocytes on the mucosal surface are frequently exposed to
      HIV-1 through contact with infected sexual partners or nursing mothers. To
      determine the plausibility that oral keratinocytes are primary targets of HIV-1,
      we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted
      manner. RESULTS: To study the fate of HIV-1, immortalized oral keratinocytes
      (OKF6/TERT-2; TERT-2 cells) were characterized for the fate of HIV-specific RNA
      and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1gag RNA was
      detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2
      cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Deltaenv-EGFP. AZT
      inhibited EGFP expression in a dose-dependent manner, suggesting that viral
      replication can be supported if receptors are bypassed. Within 3 h post
      inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and
      persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not
      detectable up to 72 h post inoculation, suggesting that HIV replication may abort
      and that infection is non-productive. Within 48 h post inoculation, however,
      virus harbored by CD4 negative TERT-2 cells trans infected co-cultured peripheral
      blood mononuclear cells (PBMCs) or MOLT4 cells (CD4+ CCR5+) by direct cell-to
      cell transfer or by releasing low levels of infectious virions. Primary tonsil
      epithelial cells also trans infected HIV-1 to permissive cells in a donor
      specific manner. CONCLUSION: Oral keratinocytes appear, therefore, to support
      stable non-replicative integration, while harboring and transmitting infectious
      X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.

PMID- 18637195
TI  - Culture creates genetic structure in the Caucasus: autosomal, mitochondrial, and
      Y-chromosomal variation in Daghestan.
AB  - BACKGROUND: Near the junction of three major continents, the Caucasus region has
      been an important thoroughfare for human migration. While the Caucasus Mountains
      have diverted human traffic to the few lowland regions that provide a gateway
      from north to south between the Caspian and Black Seas, highland populations have
      been isolated by their remote geographic location and their practice of
      patrilocal endogamy. We investigate how these cultural and historical differences
      between highland and lowland populations have affected patterns of genetic
      diversity. We test 1) whether the highland practice of patrilocal endogamy has
      generated sex-specific population relationships, and 2) whether the history of
      migration and military conquest associated with the lowland populations has left
      Central Asian genes in the Caucasus, by comparing genetic diversity and pairwise
      population relationships between Daghestani populations and reference populations
      throughout Europe and Asia for autosomal, mitochondrial, and Y-chromosomal
      markers. RESULTS: We found that the highland Daghestani populations had
      contrasting histories for the mitochondrial DNA and Y-chromosome data sets. Y
      chromosomal haplogroup diversity was reduced among highland Daghestani
      populations when compared to other populations and to highland Daghestani
      mitochondrial DNA haplogroup diversity. Lowland Daghestani populations showed
      Turkish and Central Asian affinities for both mitochondrial and Y-chromosomal
      data sets. Autosomal population histories are strongly correlated to the pattern
      observed for the mitochondrial DNA data set, while the correlation between the
      mitochondrial DNA and Y-chromosome distance matrices was weak and not
      significant. CONCLUSION: The reduced Y-chromosomal diversity exhibited by
      highland Daghestani populations is consistent with genetic drift caused by
      patrilocal endogamy. Mitochondrial and Y-chromosomal phylogeographic comparisons
      indicate a common Near Eastern origin of highland populations. Lowland Daghestani
      populations show varying influence from Near Eastern and Central Asian
      populations.

PMID- 18637196
TI  - Survival benefit of coronary-artery bypass grafting accounted for deaths in those
      who remained untreated.
AB  - BACKGROUND: Currently there are no direct estimates of mortality reduction
      afforded by coronary-artery bypass grafting (CABG) that take into account the
      deaths among patients for whom coronary revascularization was indicated but who
      did not undergo the treatment. The objective of this analysis was to compare
      survival after the treatment decision between patients who underwent CABG and
      those who remained untreated. METHODS: We used a population-based registry to
      identify patients with established coronary artery disease who were to undergo
      first-time isolated CABG. We measured the effect of surgical revascularization on
      survival after the treatment decision in two cohorts of patients categorized by
      symptoms, coronary anatomy, and left ventricular function. RESULTS: One in 10
      patients died during the five years after treatment decision. The hazard of death
      among patients who underwent CABG was 51 percent of that for the untreated group,
      the adjusted hazard ratio was 0.51 (95 percent confidence interval, 0.43 to
      0.61). The effect was stronger when CABG was performed within the recommended
      time: adjusted hazard ratios were 0.43 (95 percent confidence interval, 0.35 to
      0.53) and 0.58 (95 percent confidence interval, 0.48 to 0.70) for early and late
      intervention, respectively; chi-square for the difference between hazard ratios
      was 12.2 (P < 0.001). CONCLUSION: Estimates that account for patients who died
      before they could undergo a required CABG indicate a significant survival benefit
      of performing early surgical revascularization even for patients registered to
      undergo the operation on the non-urgent basis.

PMID- 18637197
TI  - Undetected iatrogenic lesions of the anterior femoral shaft during intramedullary
      nailing: a cadaveric study.
AB  - BACKGROUND: The incidence of undetected radiographically iatrogenic longitudinal
      splitting in the anterior cortex during intramedullary nailing of the femur has
      not been well documented. METHODS: Cadaveric study using nine pairs of fresh
      frozen femora from adult cadavers. The nine pairs of femora underwent a
      standardized antegrade intramedullary nailing and the detection of iatrogenic
      lesions, if any, was performed macroscopically and by radiographic control.
      RESULTS: Longitudinal splitting in the anterior cortex was revealed in 5 of 18
      cadaver femora macroscopically. Anterior splitting was not detectable in
      radiographic control. CONCLUSION: Longitudinal splitting in the anterior cortex
      during intramedullary nailing of the femur cannot be detected radiographically.

PMID- 18637198
TI  - Wilson protein expression, copper excretion and sweat production in sweat glands
      of Wilson disease patients and controls.
AB  - BACKGROUND: In Wilson disease, copper is not sufficiently excreted into bile due
      to the absence or malfunction of the Wilson protein copper ATPase in the
      excretory pathway of hepatocytes. Copper is found in sweat. It is unknown if the
      Wilson protein plays a role in copper excretion into sweat. It is the aim of this
      study to investigate Wilson protein expression in sweat glands and analysing its
      effects on copper excretion into sweat in controls and patients with Wilson
      disease. METHODS: Immunofluorescent analysis of the Wilson protein in skin
      samples from normal rat, LEC rat and human skin biopsies were performed.
      Pilocarpin-induced sweat gland stimulation by iontophoretic transfer adapted from
      the methods used for cystic fibrosis sweat test was used for sweat induction.
      Sweat volume, sweat copper concentration, serum ceruloplasmin and serum copper
      were analysed in 28 Wilson patients and 21 controls. RESULTS: The Wilson protein
      is expressed in human and rat sweat gland epithelia. Copper concentration in
      sweat is not significantly different between controls and Wilson patients. Wilson
      patients produce significantly smaller volumes of sweat compared to controls.
      Sweat production is partially reversible in Wilson patients under medical
      treatment for Wilson disease or after liver transplantation CONCLUSION: Wilson
      patients show a reduced sweat production with unaltered sweat copper
      concentration. The Wilson protein might play an important role in physiological
      sweat production.

PMID- 18637199
TI  - Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA
      mutant.
AB  - BACKGROUND: The current tuberculosis vaccine is a live vaccine derived from
      Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine
      substrains in use stem from one source, strain Bacille Calmette-Guerin. However,
      they differ in regions of genomic deletions, antigen expression levels,
      immunogenicity, and protective efficacy. RESULTS: As a RecA phenotype increases
      genetic stability and may contribute restricting the ongoing evolution of the
      various BCG substrains while maintaining their protective efficacy, we aimed to
      inactivate recA by allelic replacement in BCG vaccine strains representing
      different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia). Homologous
      gene replacement was achieved successfully in three out of four strains. However,
      only illegitimate recombination was observed in BCG substrain Russia. Sequence
      analyses of recA revealed that a single nucleotide insertion in the 5' part of
      recA led to a translational frameshift with an early stop codon making BCG Russia
      a natural recA mutant. At the protein level BCG Russia failed to express RecA.
      CONCLUSION: According to phylogenetic analyses BCG Russia is an ancient vaccine
      strain most closely related to the parental M. bovis. We hypothesize that recA
      inactivation in BCG Russia occurred early and is in part responsible for its high
      degree of genomic stability, resulting in a substrain that has less genetic
      alterations than other vaccine substrains with respect to M. bovis AF2122/97 wild
      type.

PMID- 18637200
TI  - Evidence against PALB2 involvement in Icelandic breast cancer susceptibility.
AB  - Several mutations in the PALB2 gene (partner and localizer of BRCA2) have been
      associated with an increased risk of breast cancer, including a founder mutation,
      1592delT, reported in Finnish breast cancer families. Although most often the
      risk is moderate, it doesn't exclude families with high-risk mutations to exist
      and such observations have been reported. To see if high-risk PALB2-mutations may
      be present in the geographically confined population of Iceland, linkage analysis
      was done on 111 individuals, thereof 61 breast cancer cases, from 9 high-risk non
      BRCA1/BRCA2 breast cancer families, targeting the PALB2 region. Also, screening
      for the 1592delT founder mutation in the 9 high-risk families and in 638
      unselected breast cancer cases was performed. The results indicate no linkage in
      any of the high-risk families and screening for the 1592delT mutation was
      negative in all samples. PALB2 appears not to be a significant factor in high
      risk breast cancer families in Iceland and the 1592delT mutation is not seen to
      be associated with breast cancer in Iceland.

PMID- 18637201
TI  - Differences in evolutionary pressure acting within highly conserved ortholog
      groups.
AB  - BACKGROUND: In highly conserved widely distributed ortholog groups, the main
      evolutionary force is assumed to be purifying selection that enforces sequence
      conservation, with most divergence occurring by accumulation of neutral
      substitutions. Using a set of ortholog groups from prokaryotes, with a single
      representative in each studied organism, we asked the question if this
      evolutionary pressure is acting similarly on different subgroups of orthologs
      defined as major lineages (e.g. Proteobacteria or Firmicutes). RESULTS: Using
      correlations in entropy measures as a proxy for evolutionary pressure, we
      observed two distinct behaviors within our ortholog collection. The first subset
      of ortholog groups, called here informational, consisted mostly of proteins
      associated with information processing (i.e. translation, transcription, DNA
      replication) and the second, the non-informational ortholog groups, mostly
      comprised of proteins involved in metabolic pathways. The evolutionary pressure
      acting on non-informational proteins is more uniform relative to their
      informational counterparts. The non-informational proteins show higher level of
      correlation between entropy profiles and more uniformity across subgroups.
      CONCLUSION: The low correlation of entropy profiles in the informational ortholog
      groups suggest that the evolutionary pressure acting on the informational
      ortholog groups is not uniform across different clades considered this study.
      This might suggest "fine-tuning" of informational proteins in each lineage
      leading to lineage-specific differences in selection. This, in turn, could make
      these proteins less exchangeable between lineages. In contrast, the uniformity of
      the selective pressure acting on the non-informational groups might allow the
      exchange of the genetic material via lateral gene transfer.

PMID- 18637202
TI  - Brain derived neurotrophic factor (BDNF) contributes to the pain hypersensitivity
      following surgical incision in the rats.
AB  - BACKGROUND: The pathogenic role of brain derived neurotrophic factor (BDNF) in
      the incisional pain is poorly understood. The present study explores the role of
      the BDNF in the incision-induced pain hypersensitivity. METHODS: A longitudinal
      incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal
      root ganglias (DRG) and spinal cords were removed at various postoperative times
      (1-72 h). Expression pattern of BDNF was determined by immunohistochemistry and
      double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve
      function was used to determine the importance of afferent nerve activity on BDNF
      expression in the DRG and spinal cord after incision. BDNF antibody was
      administered intrathecally (IT) or intraperitoneal (IP) to modulate the spinal
      BDNF or peripheral BDNF after incision. RESULTS: After hind-paw incision, the
      BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas
      thoracic BDNF remained unchanged in response to incision. The upregulated BDNF
      was mainly expressed in the large-sized neurons in DRG and the neurons and the
      primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the
      increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody
      greatly inhibited the mechanical allodynia induced by incision whereas IP
      administration had only marginal effect. CONCLUSION: The present study showed
      that incision induced the segmental upregulation of BDNF in the DRG and spinal
      cord through somatic afferent nerve transmission, and the upregulated BDNF
      contributed to the pain hypersensitivity induced by surgical incision.

PMID- 18637203
TI  - Multitrait analysis of quantitative trait loci using Bayesian composite space
      approach.
AB  - BACKGROUND: Multitrait analysis of quantitative trait loci can capture the
      maximum information of experiment. The maximum-likelihood approach and the least
      square approach have been developed to jointly analyze multiple traits, but it is
      difficult for them to include multiple QTL simultaneously into one model.
      RESULTS: In this article, we have successfully extended Bayesian composite space
      approach, which is an efficient model selection method that can easily handle
      multiple QTL, to multitrait mapping of QTL. There are many statistical
      innovations of the proposed method compared with Bayesian single trait analysis.
      The first is that the parameters for all traits are updated jointly by vector or
      matrix; secondly, for QTL in the same interval that control different traits, the
      correlation between QTL genotypes is taken into account; thirdly, the information
      about the relationship of residual error between the traits is also made good use
      of. The superiority of the new method over separate analysis was demonstrated by
      both simulated and real data. The computing program was written in FORTRAN and it
      can be available for request. CONCLUSION: The results suggest that the developed
      new method is more powerful than separate analysis.

PMID- 18637204
TI  - Sulfamethoxazole/Trimethoprim induced liver failure: a case report.
AB  - Sulfamethoxazole/Trimethoprim (SMX/TMP) is a commonly used antibiotic, its'
      known adverse reaction of hepatotoxicity leading to acute liver failure is
      considered rare. We present a case of a 22 year old female who developed jaundice
      and acute liver failure one week after taking SMX/TMP for a UTI. After an
      extensive work up, a clinical diagnosis of SMX/TMP induced liver failure was
      reached. Over the course of several weeks she made a good clinical and
      biochemical recovery with supportive care. In this case report we describe her
      clinical presentation and course, and present a brief review of the literature.

PMID- 18637205
TI  - Childhood TB epidemiology and treatment outcomes in Thailand: a TB active
      surveillance network, 2004 to 2006.
AB  - BACKGROUND: Of the 9.2 million new TB cases occurring each year, about 10% are in
      children. Because childhood TB is usually non-infectious and non-fatal, national
      programs do not prioritize childhood TB diagnosis and treatment. We reviewed data
      from a demonstration project to learn more about the epidemiology of childhood TB
      in Thailand. METHODS: In four Thai provinces and one national hospital, we
      contacted healthcare facilities monthly to record data about persons diagnosed
      with TB, assist with patient care, provide HIV counseling and testing, and obtain
      sputum for culture and susceptibility testing. We analyzed clinical and treatment
      outcome data for patients age < 15 years old registered in 2005 and 2006.
      RESULTS: Only 279 (2%) of 14,487 total cases occurred in children. The median age
      of children was 8 years (range: 4 months, 14 years). Of 197 children with
      pulmonary TB, 63 (32%) were bacteriologically-confirmed: 56 (28%) were smear
      positive and 7 (4%) were smear-negative, but culture-positive. One was diagnosed
      with multi-drug resistant TB. HIV infection was documented in 75 (27%). Thirteen
      (17%) of 75 HIV-infected children died during TB treatment compared with 4 (2%)
      of 204 not known to be HIV-infected (p < 0.01). CONCLUSION: Childhood TB is
      infrequently diagnosed in Thailand. Understanding whether this is due to absence
      of disease or diagnostic effort requires further research. HIV contributes
      substantially to the childhood TB burden in Thailand and is associated with high
      mortality.

PMID- 18637206
TI  - The influence of survivin shRNA on the cell cycle and the invasion of SW480 cells
      of colorectal carcinoma.
AB  - BACKGROUND: The objective was to understand the influence of Survivin plasmid
      with short hairpin RNA (shRNA) on the cell cycle, invasion, and the silencing
      effect of Survivin gene in the SW480 cell of colorectal carcinoma. METHODS: A
      eukaryotic expression vector, PGCH1/Survivin shRNA, a segment sequence of
      Survivin as target, was created and transfected into colorectal carcinoma cell
      line SW480 by the non-lipid method. The influence on the Survivin protein was
      analyzed by Western blotting, while the cell cycle, cell apoptosis were analyzed
      by flow cytometry, and invasion of the cell was analyzed by Transwell's chamber
      method. RESULTS: After the transfection of PGCH1/Survivin shRNA, the expression
      of Survivin protein in SW480 cells was dramatically decreased by 60.68%, in which
      the cells were stopped at G2/M phase, even though no apoptosis was detected. The
      number of transmembranous cells of the experimental group, negative control
      group, and blank control group were 14.46 +/- 2.11, 25.12 +/- 8.37, and 25.86 +/-
      7.45, respectively (P <0.05). CONCLUSION: Survivin shRNA could significantly
      reduce the expression of Survivin protein and invasion of SW480 cells. Changes in
      cell cycle were observed, but no apoptosis was induced.

PMID- 18637208
TI  - Mechanisms of arousal, alertness, and attention. Proceedings of a meeting. June
      23-29, 2007. Cold Spring Harbor, New York, USA.

PMID- 18637207
TI  - Profiling of serum and tissue high abundance acute-phase proteins of patients
      with epithelial and germ line ovarian carcinoma.
AB  - BACKGROUND: Acute-phase response involves the simultaneous altered expression of
      serum proteins in association to inflammation, infection, injury or malignancy.
      Studies of the acute-phase response usually involve determination of the levels
      of individual acute-phase serum proteins. In the present study, the acute-phase
      response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian
      carcinoma was investigated using the gel-based proteomic approach, a technique
      which allowed the simultaneous assessment of the levels of the acute-phase serum
      high abundance proteins. Data obtained were validated using ELISA and
      immunostaining of biopsy samples. RESULTS: Enhanced expression of clusterin
      (CLU), alpha1-antitrypsin, haptoglobin and leucine rich glycoprotein was detected
      in all patients. However, the levels of alpha1-antichymotrypsin (ACT) was only
      enhanced in EOCa patients, while patients with GOCa were typically characterized
      by elevated levels of ceruloplasmin but lower levels of alpha2-HS glycoprotein.
      The enhanced expression of CLU in EOCa and GOCa patients and up-regulated
      expression of ACT specifically in EOCa patients were confirmed by ELISA.
      Immunohistochemical staining of biopsy samples of EOCa and GOCa patients
      demonstrated correlation of the acute-phase protein expression. CONCLUSION:
      Patients with EOCa and GOCa demonstrated distinctive aberrant expression of serum
      and tissue high abundance acute-phase proteins compared to negative control
      women.

PMID- 18637210
TI  - Proceedings of a round table held at the 94th Italian Society of
      Otorhinolaryngology National Congress. May 23-26, 2007. Lecce, Italy.

PMID- 18637209
TI  - The use of bone marrow transplantation to treat autoimmune disease. Proceedings
      of a Center of Excellence meeting and Festschrift to honor Professor Susumu
      Ikehara. October 2007. Osaka, Japan.

PMID- 18637211
TI  - Proceedings of the Third International Conference on Hypertension and the Kidney,
      February 2002, Madrid, Spain.

PMID- 18637212
TI  - Proceedings of the 2nd Heart-Brain Summit. June 7-8, 2007. Cleveland, Ohio, USA.

PMID- 18637213
TI  - Endocannabinoids in endocrinology, metabolism and cardiovascular diseases,
      scientific background and clinical perspectives. Proceedings of a workshop. July
      2007. Padua, Italy.

PMID- 18637214
TI  - In this issue: community care, healing, and excellence in research.

PMID- 18637216
TI  - Darzi set to put commissioning at centre stage.

PMID- 18637217
TI  - Radical ideas can keep service out of casualty.

PMID- 18637218
TI  - Malcolm Lowe-Lauri on co-operation.

PMID- 18637219
TI  - Why NHS must keep an eye on the other half.

PMID- 18637220
TI  - Data briefing. Wider engagement in joint assessment.

PMID- 18637221
TI  - Anyone here a doctor who speaks nurse?
AB  - Patient safety errors are often caused by the NHS being a "Tower of Babel", with
      many "languages" spoken. Staff "tribes" often focus on their own agendas, rather
      than on the patients' health. The National Patient Safety Campaign is aiming to
      make the topic a priority of staff, patients and carers.

PMID- 18637222
TI  - Integrated care. Polycautious.

PMID- 18637223
TI  - Coaching. Project you.

PMID- 18637224
TI  - Mutual fund investing: what you need to consider when choosing your mutual funds.

PMID- 18637225
TI  - Contrast-enhanced MRA of intracranial vessels.
AB  - Despite the possibility of performing high quality and diagnostically useful
      examination of the intracranial vasculature using time-of-fight (TOF) and phase
      contrast (PC) MR angiography, there are still some intrinsic technical problems
      that limit the application of these techniques. Many of these problems,
      particulary those related to flow effects, can be avoided by the use of a
      suitable contrast agent. To avoid the problem of super-imposition of veins,
      ultrafast gradient echo MRA techniques with very short TR and TE have been
      developed. Although the precise sequence parameters vary between different
      manufacturers, they are similar. The choice between a time resolved or high
      spatial resolution CE-MRA technique is dependent upon the precise clinical
      application. The most common applications include the study of cerebral
      aneurysms, arterio-venous malformations, dural arterio-venous fistulas and venous
      diseases.

PMID- 18637226
TI  - MRA of the carotid arteries.
AB  - Magnetic resonance angiography (MRA) is increasingly used as a non-invasive
      method to assess carotid arteries. Contrast-enhanced MRA (CE-MRA) has benefited
      from rapid technological developments, including specific hardware and pulse
      sequence design. In the evaluation of stenoses of the extracranial internal
      carotid artery (ICA), CE-MRA using "first generation" CE-MRA gadolinium (Gd)
      based chelates can be a substitute for conventional digital subtraction
      angiography (DSA), although CE-MRA tends to overestimate the degree of stenosis.
      Studies describing the use of high-relaxivity contrast agents like gadobenate
      dimeglumine (Gd-BOPTA) reveal that this agent is safe and well tolerated for CE
      MRA. The use of Gd-BOPTA shows significantly better quantitative and qualitative
      performance than carotid CE-MRA using first generation Gd-based chelates. In
      fact, CE-MRA with Gd-BOTPA provides information comparable to that attainable
      with rotational DSA. In conclusion, high-relaxivity contrast agents combined with
      dedicated MRA software appear to be optimal for achieving high-quality evaluation
      of the carotid arteries.

PMID- 18637227
TI  - MultiHance in MRA of peripheral vasculature.
AB  - Magnetic resonance angiography (MRA) is a cost effective technique able to detect
      and quantify stenoses, provide sub-millimeter resolution with full arterial
      coverage, and show true vessel delineation without artifacts.The quality of
      images obtained with gadolinium-enhanced MRA depends on the gradient system,
      coil, sequence design, and contrast agent (volume, dose and injection rate). MRA
      protocols are evolving from standard k-space sampling (linear from the periphery
      or the center) to elliptic centric view ordering and to time-resolved MRA.
      Finally, the gadolinium-based contrast agent Gd-BOPTA (gadobenate dimeglumine,
      MultiHance; Bracco Imaging, Milan, Italy) offers considerably greater imaging
      efficacy compared to conventional gadolinium chelates,because identical results
      can be obtained at lower doses. In conclusion, MRA of the peripheral vasculature
      is a simple and fast technique, which permits evaluation of a large field of view
      without risk of radiation exposure.

PMID- 18637228
TI  - CE-MRA in paediatric patients.
AB  - Contrast enhanced magnetic resonance angiography (CE-MRA) is an established
      diagnostic method for evaluating vascular disease in adults. However, the use of
      MRA techniques has spread more slowly in children owing to significant technical
      challenges in the paediatric population. This article discusses the indications
      for CE-MRA in paediatric patients, the techniques employed and the imaging
      findings expected from MRA of children with vascular disease. In particular, the
      application of "time-resolved" CE-MRA is discussed and clinical case examples are
      provided to highlight the broad clinical application of this technique in
      paediatric vascular disease.

PMID- 18637229
TI  - New challenges in MDCT.
AB  - The performance of computed tomography has approximately doubled every two years
      since the mid 1980s. The introduction of multidetector CT (MDCT) has sustained
      this trend. While 4-slice scanners were able to scan faster or with higher
      resolution than single slice units, 16-slice scanners introduced fast isotropic
      imaging and 32-to 64-slice scanners made it possible to combine ECG-gated cardiac
      evaluation with other CT applications. New technologies such as z-flying focal
      spot improve image quality and artifact behaviour. At present, however, CT faces
      a number of challenges that make it difficult to extrapolate performance into the
      future. The most important challenge is the relationship between spatial
      resolution and image noise; for identical image noise at higher spatial
      resolution, radiation dose will have to be increased substantially. For example,
      if the spatial resolution is to be increased by a factor of 2 in all spatial
      directions, the dose will need to be increased by 2(4)=16. This x(4) relationship
      results from the lower number of quanta that penetrate a smaller voxel and from
      the fact that CT images have to be reconstructed from projectional data. Dose
      containment and noise suppression techniques will therefore become the defining
      factors for further improvement of spatial resolution in CT. Increasing detector
      width will become important for CT perfusion imaging but will face challenges
      from scattered radiation, cone beam artifacts and overscanning. Faster effective
      rotation speeds together with improved dose efficiency of image reconstruction
      will become the main challenges for cardiac CT imaging.

PMID- 18637230
TI  - Scan and contrast administration principles of MDCT.
AB  - Because of its fast scan speed, multi-detector row CT (MDCT) imposes a challenge
      to optimization of contrast enhancement and scan timing. However, when this
      challenge is overcome with the use of precisely designed protocols, MDCT provides
      us with an opportunity to use contrast medium more efficiently and flexibly than
      with single-detector row CT (SDCT). To fully achieve the benefits of MDCT, it is
      crucial for radiologists and technologists to 1) understand the factors that
      determine contrast enhancement and scan timing for MDCT, and 2) identify the
      required modifications in protocol design to optimize contrast enhancement for
      MDCT. Clinical considerations for CTA and hepatic imaging are described in this
      article.

PMID- 18637231
TI  - How to design injection protocols for multiple detector-row CT angiography
      (MDCTA).
AB  - The basis of the development of optimal injection protocols for multiple detector
      row CT-angiography is knowledge of the physiological and pharmacokinetic
      principles of arterial enhancement. This article reviews the key rules of early
      arterial contrast medium dynamics: (1) Arterial enhancement is directly
      proportional to the iodine administration rate (iodine flux), and can be
      controlled by the injection flow rate and the iodine concentration of the
      contrast medium; (2) Arterial enhancement continuously increases over time with
      longer injection durations, due to the cumulative effects of bolus broadening and
      recirculation; (3) The strength of an individual's enhancement response to
      intravenously administered CM depends primarily on the patient's cardiac output
      and correlates inversely with body weight. In CTA, any of the following
      strategies can be employed alone, or in combination, to achieve adequate arterial
      enhancement in spite of short acquisition times: Increasing the injection rate,
      using higher concentration CM or increasing the injection duration (and scanning
      delay) relative to the scan time. Both injection volumes and flow rates should be
      adjusted to body weight, at least for patients < or =60 kg and > or =90kg BW.
      Rationally designed injection protocols based on physiological concepts allow
      optimal CM utilisation and take full advantage of the technical capabilities
      offered by modern MDCT scanners.

PMID- 18637232
TI  - Optimized imaging of pulmonary embolism.
AB  - Pulmonary embolism (PE) is a common disease with considerable mortality. There
      are no specific signs or symptoms of PE; the diagnosis relies on imaging tests.
      The development of multi-detector computed tomography has led to an improvement
      in the diagnosis of PE due to faster scanning and improved spatial resolution
      along the longitudinal axis of the patient. Apart from fast scanning and thin
      collimation, optimal arterial attenuation remains one of the most crucial
      determinants of sufficient depiction of the pulmonary arteries. Arterial
      attenuation over time is generally determined by iodine flow concentration, which
      may be increased either by raising the contrast medium flow rate, and/or by using
      a high iodine concentration contrast medium. The scan duration necessary for
      imaging the whole thorax ranges from about 20 s with a four-detector row scanner
      to about 5 s with a 64-detector row detector scanner. The collimation ranges from
      0.5 mm to 1 mm depending on the scanner used. This enables the most detailed
      display of the pulmonary arteries. Bolus triggering devices are a valuable tool
      for accurate timing of scanning. The administration of the contrast material
      bolus is performed using a power injector at a flow rate of about 4 mL/s. A
      saline flush immediately after contrast material administration avoids pooling of
      the contrast material in the arm veins and in the injection system and reduces
      perivenous artifacts in the superior vena cava. The use of a high concentration
      contrast material significantly improves attenuation of the pulmonary arteries
      leading to better visualisation of sub-segmental and lower order pulmonary
      arteries in multi-row-detector-CTA. In addition, the higher attenuation may
      improve the conspicuity of emboli within the pulmonary arteries.

PMID- 18637233
TI  - Advances in imaging protocols for cardiac MDCT: from 16- to 64-row multidetector
      computed tomography.
AB  - Coronary artery disease (CAD) is the leading cause of morbidity and mortality in
      the Western world. Since the majority of all invasive diagnostic coronary
      angiography procedures are not followed by therapeutic interventions, interest is
      growing in noninvasive technologies to diagnose and visualize CAD. The most
      promising of these is multislice spiral computed tomography (MSCT), which can
      visualize human coronary arteries in vivo noninvasively. Since 1999, this
      technique has improved rapidly, offering faster gantry rotation times and smaller
      voxel sizes. The image quality has become significantly more stable and MSCT has
      become a robust imaging modality. Beginning with 4-slice scanners in 1999, the
      latest scanner generation employs 64 slices. The present article summarizes the
      technical principles, image protocols and possible clinical applications of the
      current 64-row scanners.

PMID- 18637234
TI  - Abdominal MDCT: protocols and contrast considerations.
AB  - Multidetector computed tomography (MDCT), is the latest breakthrough in CT
      technology. Thin sections can now be acquired a routine basis in a single
      breathhold with 3D-isotropic reconstructions. This results in improved lesion
      detection of benign as well as malignant abdominal tumours. The ability to scan
      through the entire abdomen in seconds allows multiphasic acquisitions. Therefore
      precise timing and optimized contrast is of great importance. Hypervascularized
      solid abdominal tumours are best depicted within the time generally regarded as
      the arterial dominant phase in MDCT, conversely hypovascular lesions are best
      depicted during venous phase imaging. The acquisition of an early arterial phase
      provides precise documentation of the arterial vascular system and should be
      obtained in preoperative abdominal imaging. Three clear separate circulatory
      phases enable best results in the pretherapeutic work-up of abdominal patients.
      Regarding follow-up oncologic work-up in colorectal metastatic disease a venous
      dominant phase might be the optimal protocol. Regarding contrast optimization,
      the traditional concept of imaging, where the injection duration equals the
      scanning duration cannot be used without modifications. To ensure adequate vessel
      opacification as well as soft tissue imaging with fast MDCT acquisitions, the
      iodine administration rate needs to be increased. This can be achieved either by
      an increase of injection flow rate or -more conveniently- by using a higher
      iodine concentration of the contrast medium. Especially for hypervascular
      tumours, e.g. HCC, a considerably to far higher contrasts can be achieved using
      higher concentrated contrast material. The overall improvement in precise timing
      and better visibility enable a comprehensive approach to abdominal imaging in
      MDCT.

PMID- 18637235
TI  - Our experiences using contrast-enhanced ultrasound in focal liver lesions.
AB  - In investigation of liver lesions, continuous observation of contrast behaviour
      is possible with, and is an important strength of, contrast ultrasound at a low
      mechanical index. In many institutions contrast enchanced ultrasound using
      SonoVue in focal liver lesions has become a routine investigation. At our
      department contrast ultrasound is predominantly used to further characterise
      lesions which appear uncharacteristic at grey-scale ultrasound. We were able to
      show that contrast ultrasound with SonoVue is superior or equal to CT in the
      majority of cases. Using contrast ultrasound after inconclusive grey-scale
      ultrasound testing often enables adequate lesion characterisation without the
      necessity of CT or MRI.

PMID- 18637236
TI  - European federation of societies for ultrasound in medicine and biology (EFSUMB)
      guidelines for the use of contrast agents in liver ultrasound: what is the impact
      in clinical practice?
AB  - Ultrasound is the most commonly used liver imaging modality worldwide.
      Unfortunately, ultrasound has limited sensitivity in the detection of small
      tumour nodules. Moreover, ultrasound findings are often non-specific, as there is
      enough variability and overlap in the appearance of benign and malignant liver
      lesions to make a definite distinction problematic. Recently, the introduction of
      microbubble contrast agents and the development of contrast-specific techniques
      have opened new prospects in liver ultrasound. The advent of second-generation
      agents that have higher harmonic emission capabilities has been instrumental in
      improving the easiness and the reproducibility of the examination. Over the past
      few years, several reports have shown that real-time contrast-enhanced ultrasound
      can substantially improve detection and characterization of focal liver lesions
      with respect to baseline studies. With the publication of the guidelines for the
      use of contrast agents in liver ultrasound by the European Federation of
      Societies for Ultrasound in Medicine and Biology (EFSUMB), contrast-enhanced
      ultrasound has entered clinical practice. The guidelines define the indications
      and recommendations for the use of contrast agents in focal liver lesion
      detection, characterization and posttreatment follow-up. In this paper, we
      discuss the impact of EFSUMB guidelines on diagnostic protocols currently adopted
      in liver imaging with regard to four clinical scenarios: (1) characterization of
      focal liver lesions of incidental detection; (2) diagnosis of HCC in patients
      with cirrhosis; (3) detection of hepatic metastases in oncology patients; (4)
      guidance and assessment of the outcome of percutaneous tumour ablation
      procedures.

PMID- 18637237
TI  - Quantification of enhancement in contrast ultrasound: a tool for monitoring of
      therapies in liver metastases.
AB  - Ultrasound techniques are presented using the contrast agent SonoVue (Bracco,
      Italy) for microvascular imaging of liver metastases and for the detection of
      treatment-related changes in tumour perfusion. Technical requirements and
      examination protocols for contrast-enhanced ultrasound (CEUS) in the detection of
      microvascularity are described. Procedures for the quantitative analysis of
      perfusion in follow-up examinations are explained. Compared to contrast-enhanced
      computed tomography, low-MI (mechanical index) CEUS with SonoVue better reflected
      the arterial perfusion of liver metastases. Changes of tumour perfusion after
      stereotactic radiotherapy or chemotherapy of liver metastases could be
      sensitively detected using CEUS. In addition, possible changes of the liver
      perfusion after therapy could be assessed. Replenishment kinetics of the contrast
      agent allowed for a quantitative analysis of the arterial and portal venous
      perfusion in the tumour and the liver tissue. CEUS is a promising method to non
      invasively monitor systemic or local-ablative therapies of liver metastases by
      sensitively detecting changes of tumour perfusion.

PMID- 18637238
TI  - The use of contrast-enhanced US in renal transplant: first results and potential
      clinical benefit.
AB  - INTRODUCTION AND PURPOSE: Little use has been made so far of the intrinsic
      advantages of ultrasound (US) for quantifying tissue perfusion of parenchymal
      organs, that is, its high spatial and temporal resolution and immediate
      availability in any clinical situation. Since acute rejection of a kidney graft
      primarily involves the sub-capsular capillaries, early and detailed evaluation of
      blood flow in this area is highly desirable. Using a clinically established US
      contrast medium (USCM) of the second generation and improved US technology, we
      performed a study to investigate whether it is possible to adequately diagnose
      rejection after kidney transplant by evaluating the arterial inflow of an echo
      enhancer. PATIENTS AND METHODS: A total of 32 patients underwent US examination
      with an echo enhancer (1.6 ml SonoVue, Bracco-Altana) 5 to 7 days after kidney
      transplantation. The examinations were performed using the Aplio US system
      (Toshiba) with a 3.5-MHz transducer and micro flow imaging (MI 0.1). Contrast
      medium inflow was determined in the renal artery and the renal cortex using
      Windows-based, time-intensity curve (TIC) software. The temporal difference in
      contrast medium inflow between the two vascular territories was determined (Dt =
      time baseline renal cortex--time baseline renal artery). Patients with primary
      graft failure (no function until day 3) were excluded (number of patients, n=2).
      In patients with large peri-renal hematoma (n=6), the effect of US on perfusion
      was determined and the results in these cases (hematoma group) were compared with
      those in the remaining patients. RESULTS: Seventeen patients had uneventful
      clinical course (resistance index (RI) on day 7: 0.75+/-0.11). In this group US
      demonstrated a uniform inflow of the CM. The calculated slopes were comparable
      with those of the interlobar artery and renal cortex (no rejection group). Seven
      patients showed histologically confirmed acute rejection on days 5 to 7 after
      transplantation (rejection group). The RI in this group was at the upper limit on
      day 7 (0.77+/-0.08). The temporal difference in CM arrival between the two
      vascular territories was greater in the rejection group (2.27+/-0.73 s) compared
      with the normal group (0.97+/-0.62 s, p<0.05, p=significance). The difference was
      also increased in the hematoma group (1.5+/-1.3 s, p>0.05). The size of the
      hematoma correlated with the extent to which USCM inflow was altered. In only two
      cases, the USCM examination demonstrated a perfusion defect. CONCLUSIONS: The use
      of echo enhancers has potential to diagnose acute kidney graft rejection in its
      early stages. US not only identifies kidney perfusion defects but also provides
      information on the effect of a large peri-renal hematoma.

PMID- 18637239
TI  - Value of contrast-enhanced ultrasound in rheumatic disease.
AB  - Ultrasound (US) is a useful tool in the assessment of rheumatic disease. It
      permits assessment of early erosive changes and vascularity detection in synovial
      proliferation, caused by inflammatory activity by using colour/power Doppler US
      (CDUS/PDUS). In the detection of slow flow and flow in small vessels, the
      CDUS/PDUS technique is limited. Contrast enhanced US can improve the detection of
      inflammatory vascularity but is not yet included in routine diagnosis of this
      condition. However, contrast enhanced US shows promising results in diagnosis,
      assessment of disease activity and follow up of inflammatory rheumatic diseases.

PMID- 18637240
TI  - [Use of CR in the detection of present gastric cancer: diagnostic aspects].
AB  - The authors describe the state-of-the-art of gastric cancer detection in detail
      and show the current principles of its radiodiagnosis. They provide a detailed
      explanation for that radiodiagnosis should be urgently returned into
      gastroenterology as an equal with endoscopy, which is based on the existing
      tendency for the major morphological types of gastric cancer to appear. The
      present-day capacities of radiodiagnosis of gastric cancer are mainly based on
      the introduction of the digital technologies into traditional radiology, which
      will replace the analog imaging principle in the foreseeable future. The authors
      present their data of examining 300 gastric cancer cases diagnosed by the CR
      system and later verified by a morphological study of resected gastric specimens.
      They emphasize that intraparietally growing gastric cancer is frequently
      inaccessible for endoscopy long, which determines the need for two basic
      procedures (radiodiagnosis and endoscopy) coexisting on a par for the detection
      of gastric cancer. They are sure that computed radiology (CR) will be the most
      acceptable way of changing traditional radiology to the digital imaging principle
      in primary, municipal health care in the near future.

PMID- 18637241
TI  - Preparing for pumped prices. Fuel costs likely to raise production, delivery
      fees.

PMID- 18637242
TI  - HHS breaks out flu guidelines ... but agency must support pandemic plan: sources.

PMID- 18637243
TI  - Judge overrules CMS. HHS violated Medicare bad-debt policy.

PMID- 18637244
TI  - That's the competitive spirit. Series of newsworthy events could help anchor
      change in the marketplace.

PMID- 18637245
TI  - Labour vision let down by reforms.

PMID- 18637246
TI  - Failed, fired but not yet fixed: the new realities.

PMID- 18637247
TI  - Simon Stevens on China's plans for healthcare.

PMID- 18637248
TI  - The questions to ask yourself about policy.

PMID- 18637249
TI  - Data briefing. Comparison across and within nations.

PMID- 18637250
TI  - Shock of the new.

PMID- 18637251
TI  - Clinical partnership. Is the doctor as we know it a museum piece.

PMID- 18637252
TI  - Health inequalities. Up to the mark in primary care.

PMID- 18637254
TI  - Proceedings of the 31st International Symposium on High Performance Liquid Phase
      Separations and Related Techniques. June 17-21, 2007. Ghent, Belgium.

PMID- 18637253
TI  - Workforce planning. Great strides in six strong steps.

PMID- 18637255
TI  - Festschrift and proceedings of the Russell V. Baudinette Memorial Symposium.
      Adelaide, South Australia, Australia. October 1-2, 2005.

PMID- 18637256
TI  - Is it really time to give up on the hope of finding a preventative HIV vaccine?
      Experts offer a mixed review of the vaccine's future.

PMID- 18637257
TI  - 'Healthy Relationships' empower HIV-infected women and encourage safe sex habits.
      Condom use, adherence increased.

PMID- 18637258
TI  - FDA issues warning for nonoxynol-9 products.

PMID- 18637259
TI  - Research product developed active, engaged consumer advisory board.

PMID- 18637260
TI  - Adherence strategies. Religion is important difference among HIV-infected
      Southern minority population. Adherence barriers largely are the same as the
      coasts.

PMID- 18637261
TI  - FDA notifications. VITROS anti-HIV test is approved.

PMID- 18637262
TI  - FDA notifications. Atazanavir capsule label is updated for pediatric patients.

PMID- 18637263
TI  - [Usage of beta-adrenolytic agents in patients with chronic pulmonary obstructive
      disease].
AB  - Beta-blockers are commonly used in the contemporary pharmacotherapy. They are
      considered the drugs of choice in the treatment of many, especially
      cardiological, disorders. Chronic obstructive pulmonary disease (COPD) is a very
      common disease, which is classified as the fourth cause of the chronic morbidity
      and mortality in the USA. Frequent occurrence, as well as the fact that some risk
      factors, such as cigarette smoking, are common for both COPD and cardiovascular
      diseases cause that the number of patients suffering from their coexistence is
      increasing. Because first beta-blockers had a strong bronchoconstrictory effect,
      their use is contraindicated in conditions associated with airway obstruction.
      This review was aimed to investigate the safety of using of beta-blockers in
      patients with COPD. We try to answer whether selective beta-blockers and so
      called hybrid beta-blockers are safe for patients suffering from this disorder.
      We also try to elaborate some therapeutic recommendations.

PMID- 18637265
TI  - Second meeting of National Influenza Centres--Western Pacific and South-East Asia
      regions.

PMID- 18637264
TI  - [Modification and optimization of PCR methods for detection of MIE region from
      human herpesvirus 5].
AB  - Human herpesvirus 5 (HHV-5, formerly known as CMV) is a beta-herpesvirus widely
      spread within a population. Thus, HHV-5 infections are a serious matter of
      concern in a group of immunocompromised patients. The goal of the study was
      modification and optimization of conventional PCR method developed for the
      detection of HHV-5 DNA to the real-time variant (RTmPCR) and determination of
      analytical resolution of the modified methods. Thirty plasma samples were tested
      for the presence of HHV-5 DNA using the LightCycler system with two different
      methods--one with SYBR Green I fluorochrome method and second one using TaqMan
      fluorescent probes and a qualitative in-house gel-stained PCR assay using primers
      that amplify part of HHV-5 MIE gene. The analytical sensitivity of real-time PCR
      assay was tested using serial dilutions of HHV-5 DNA in range between 10(0) and
      10(-6). For comparison typical end-point detected PCR for cytomegalovirus
      detection with the same DNA dilutions was made. The sensitivity of novel method
      was about 100-fold higher than older one. Both LightCycler assays detected HHV-5
      DNA in 27 samples, also which were negative by the gel-stained PCR. Analysis of
      the available clinical and serological data associated with these samples
      suggested that the real-time results in all of these cases were true positive.
      The conclusion is that real-time PCR methods are more sensitive than the
      conventional PCR used in this study. The additional sensitivity was valuable for
      detection of patients with low-copy viremia. The high level of sensitivity,
      specificity, accuracy, and rapidity provided by the LightCycler instrument are
      favorable for the use of this system in the detection of HHV-5 DNA in clinical
      specimens.

PMID- 18637266
TI  - Report from the Inter-American Conference on Onchocerciasis, November 2007.

PMID- 18637267
TI  - Influenza.

PMID- 18637268
TI  - Occupational asthma a risk for veterinarians.

PMID- 18637269
TI  - Traveling with her mother's tastes: the negotiation of gender, race, and location
      in wonderful adventures of Mrs. Seacole in many lands.

PMID- 18637272
TI  - Squalor and rough justice in Watford.

PMID- 18637271
TI  - Expression changes in EZH2, but not in BMI-1, SIRT1, DNMT1 or DNMT3B are
      associated with DNA methylation changes in prostate cancer.
AB  - The polycomb proteins BMI-1, EZH2, and SIRT1 are characteristic components of the
      PRC1, PRC2, and PRC4 repressor complexes, respectively, that modify chromatin.
      Moreover, EZH2 may influence DNA methylation by direct interaction with DNA
      methyltransferases. EZH2 expression increases during prostate cancer progression,
      whereas BMI-1 and SIRT1 are not well investigated. Like EZH2 expression, DNA
      methylation alterations escalate in higher stage prostate cancers, raising the
      question whether these epigenetic changes are related. Expression of EZH2, BMI-1,
      SIRT1, and the DNA methyltransferases DNMT1 and DNMT3B measured by qRT-PCR in 47
      primary prostate cancers was compared to APC, ASC, GSTP1, RARB2, and RASSF1A
      hypermethylation and LINE-1 hypomethylation. SIRT1 and DNMT3B were overexpressed
      in cancerous over benign tissues, whereas BMI-1 was rather downregulated and
      DNMT1 significantly diminished. Nevertheless, cancers with higher DNMT1 and BMI-1
      expression had worse clinical characteristics, as did those with elevated EZH2.
      In particular, above median DNMT1 expression predicted a worse prognosis. EZH2
      and SIRT1 overexpression were well correlated with increased MKI67.
      Immunohistochemistry confirmed limited EZH2 and heterogeneous DNMT3B
      overexpression and explained the decrease in BMI-1 by pronounced heterogeneity
      among tumor cells. EZH2 overexpression, specifically among all factors
      investigated, was associated with more frequent hypermethylation, in particular
      of GSTP1 and RARB2, and also with LINE-1 hypomethylation. Our data reveal complex
      changes in the composition of polycomb repressor complexes in prostate cancer.
      Heterogeneously expressed BMI-1 and slightly increased EZH2 may characterize less
      malignant cancers, whereas more aggressive cases express both at higher levels.
      SIRT1 appears to be generally increased in prostate cancers. Intriguingly, our
      data suggest a direct influence of increased EZH2 on altered DNA methylation
      patterns in prostate cancer.

PMID- 18637273
TI  - Republican friendship: Manuela Saenz writes women into the nation, 1835-1856.

PMID- 18637274
TI  - On the mend: the Ninth Circuit gives San Francisco's Health Care Security
      Ordinance the green light (for now).

PMID- 18637276
TI  - [Commentary to the article: Buszman P, Kiesz SR, Bochenek A, et al. Acute and
      late outcomes of unprotected left main stenting in comparison with surgical
      revascularization. J Am Coll Cardiol 2008;51:538-45].

PMID- 18637275
TI  - Family control, bridal pregnancy, and illegitimacy.

PMID- 18637279
TI  - [Home care system in communities. Interview by Manabu Sakuta].

PMID- 18637278
TI  - Convict artefacts from the Civil Hospital privy on Norfolk Island.

PMID- 18637280
TI  - Office based non-oncology urology trials.

PMID- 18637281
TI  - Every procurable object: a functional analysis of the Ross Factory archaeological
      collection.

PMID- 18637282
TI  - Open clinical uro-oncology trials in Canada.

PMID- 18637283
TI  - Re: Pheochromocytoma of the urinary bladder.

PMID- 18637284
TI  - Structure-related clustering of gene expression fingerprints of thp-1 cells
      exposed to smaller polycyclic aromatic hydrocarbons.
AB  - This study was undertaken to test the hypothesis that structurally similar PAHs
      induce similar gene expression profiles. THP-1 cells were exposed to a series of
      12 selected PAHs at 50 microM for 24 hours and gene expressions profiles were
      analyzed using both unsupervised and supervised methods. Clustering analysis of
      gene expression profiles revealed that the 12 tested chemicals were grouped into
      five clusters. Within each cluster, the gene expression profiles are more similar
      to each other than to the ones outside the cluster. One-methylanthracene and 1
      methylfluorene were found to have the most similar profiles; dibenzothiophene and
      dibenzofuran were found to share common profiles with fluorine. As expression
      pattern comparisons were expanded, similarity in genomic fingerprint dropped off
      dramatically. Prediction analysis of microarrays (PAM) based on the clustering
      pattern generated 49 predictor genes that can be used for sample discrimination.
      Moreover, a significant analysis of Microarrays (SAM) identified 598 genes being
      modulated by tested chemicals with a variety of biological processes, such as
      cell cycle, metabolism, and protein binding and KEGG pathways being significantly
      (p < 0.05) affected. It is feasible to distinguish structurally different PAHs
      based on their genomic fingerprints, which are mechanism based.

PMID- 18637286
TI  - [How to train child psychiatrists].

PMID- 18637287
TI  - [Training in child psychiatry].

PMID- 18637288
TI  - [Pediatric views on child psychiatry].

PMID- 18637289
TI  - [Training of child and adolescent psychiatrists].

PMID- 18637290
TI  - [Additional proposal for training of child and adolescent psychiatrists].

PMID- 18637291
TI  - [Developmental disorders and related matters].

PMID- 18637292
TI  - [Concepts and physiopathology of mental disorders in childhood and adolescence].

PMID- 18637293
TI  - Ghostwriting.

PMID- 18637294
TI  - Task shifting or power shedding?

PMID- 18637295
TI  - Humans--a threat to humanity.

PMID- 18637296
TI  - The season cometh ... yet again!

PMID- 18637297
TI  - Access to parenteral phenobarbitone.

PMID- 18637298
TI  - State doctor recruitment--key official in corruption probe.

PMID- 18637299
TI  - Probe into alleged treatment refusal.

PMID- 18637300
TI  - No disasters yet, please--we're catching up.

PMID- 18637301
TI  - When best practice is bad medicine: a new approach to rationing tertiary health
      services in South Africa.

PMID- 18637302
TI  - Improving injection safety.

PMID- 18637303
TI  - Spinal tuberculosis: diagnostic biopsy is mandatory.

PMID- 18637304
TI  - An alcoholic's series of unfortunate events.

PMID- 18637305
TI  - NICE rationing of specialised health care services for South Africa?

PMID- 18637306
TI  - Survival after massive intentional overdose of paraquat.

PMID- 18637307
TI  - Coronary spasm and thrombosis in a bodybuilder using a nutritional supplement
      containing synephrine, octopamine, tyramine and caffeine.

PMID- 18637308
TI  - Involving African traditional health practitioners in HIV/ AIDS interventions.

PMID- 18637309
TI  - Determinants and treatment of hypertension in South Africans: the first
      Demographic and Health Survey.
AB  - OBJECTIVES: To identify the groups of patients with high prevalence and poor
      control of hypertension in South Africa. METHODS: In the first national
      Demographic and Health Survey, 12 952 randomly selected South Africans aged 15
      years and older were surveyed. Trained interviewers completed questionnaires on
      socio-demographic characteristics, lifestyle and the management of hypertension.
      This cross-sectional survey included blood pressure, height and weight
      measurements. Logistic regression analyses identified the determinants of
      hypertension and the treatment status. RESULTS: A high risk of hypertension was
      associated with less than tertiary education, older age groups, overweight and
      obese people, excess alcohol use, and a family history of stroke and
      hypertension. Hypertension risk was lowest in rural blacks and significantly
      higher in obese black women than in women with a normal body mass index. Improved
      hypertension control was found in the wealthy, women, older persons, Asians, and
      persons with medical insurance. CONCLUSIONS: Rural black people had lower
      hypertension prevalence rates than the other groups. Poorer, younger men without
      health insurance had the worst level of hypertension control.

PMID- 18637310
TI  - Association of tooth loss with hypertension.
AB  - OBJECTIVE: Hypertension may result from changes in dietary quality and nutrient
      intake. We therefore sought to determine the epidemiological association between
      tooth loss and hypertension in South African adults. METHODS: This is a secondary
      data analysis of a cross-sectional survey of a nationally representative sample
      of adults aged 25 - 70 years who participated in the South African Demographic
      and Health Survey during 1998 (N = 9 098). The primary data were collected using
      a validated questionnaire, which included information on past experience of tooth
      loss (partial or complete), use of dental services, tobacco use and other known
      risk factors for hypertension. Hypertension was defined as having a measured
      average blood pressure (BP) > or = 160/95 mmHg and/or taking antihypertensive
      medication. RESULTS: The prevalences of hypertension, any tooth loss and complete
      edentulousness were 18.1%, 72.2% and 9.4% respectively. Tooth loss was more
      common among overweight/obese respondents than among those with a normal body
      mass index (76.7% v. 66.7%; p < 0.01). Compared with the fully dentate
      respondents, the completely edentulous respondents had mean systolic and
      diastolic BPs that were respectively 12 mmHg and 5 mmHg higher. After adjusting
      for known risk factors for hypertension in a multiple logistic regression model,
      being completely edentulous remained significantly associated with hypertension
      (odds ratio 1.35, 95% confidence interval 1.02 - 1.78). The estimated population
      attributable fraction of hypertension resulting from complete edentulousness was
      10%. CONCLUSIONS: The findings suggest that complete edentulousness is a risk
      indicator for hypertension in South Africa and highlights the importance of
      primary care practitioner involvement in oral health promotion.

PMID- 18637311
TI  - A contrast-enhanced ultrasound study of benign and malignant breast tissue.
AB  - OBJECTIVE: To determine the diagnostic value of haemodynamic contrast-enhanced
      ultrasound assessment in benign and malignant breast tissue, using histological
      examination as the reference standard. METHODS: An HDI 5000 Phillips ultrasound
      scanner with microvascular imaging software and 2.5 ml SonoVue (Bracco spa,
      Milan) contrast was used to scan 50 consecutive patients (32 malignant and 18
      benign, 49 with histologically confirmed breast lesions). Time-intensity curves
      of the regions of interest (ROI) placed over the lesional and normal breast
      tissues were acquired using QLAB software. The area under the curve (AUC), time
      to peak (TTP), in-flow gradient (IFG) and peak enhancement (PE) were determined
      in a standardised manner for each focal breast lesion and the control/normal
      breast. IFG and AUC in the periphery, and PE and AUC in the centre of the
      lesions, differed significantly between malignant and benign tumours. In a
      logistical regression model, AUC in the periphery and the ratio of PE at the
      tumour centre to that of normal breast were independently predictive of
      malignancy (p < 0.001), achieving a diagnostic sensitivity of 97% and a
      specificity of 80% in the 41 tumours in which central vessels could be
      distinguished. CONCLUSION: Haemodynamic contrast-enhanced ultrasound assessment
      can be used to distinguish between benign and malignant breast lesions.

PMID- 18637312
TI  - Multiple sclerosis in South Africa.
AB  - Since there are no well-documented epidemiological studies on multiple sclerosis
      (MS) in South Africa, we devised a questionnaire to determine qualitative data.
      Responses were obtained from 430 patients: 91% had magnetic resonance imaging
      (MRI) scans, 64% had lumbar punctures and 49% had evoked potentials to establish
      the diagnosis of MS. A total of 71% of the respondents were aged 30 - 59 years,
      73% were female, and 89% were white. In terms of MS type, 46% had relapsing
      remitting MS, 13% secondary progressive MS, 12% primary progressive MS, 12%
      benign MS, and 17% not known. Disease-modifying treatment was not used by 32% of
      respondents, and 30% were treated with methotrexate and 22% with interferon beta.
      These findings are similar to those in the literature, except for the under
      utilisation of interferons as disease-modifying treatment.

PMID- 18637313
TI  - Risky sexual behaviours of high-school pupils in an era of HIV and AIDS.
AB  - OBJECTIVE: To identify risky sexual behaviours and demographic factors that place
      high-school pupils at risk of HIV and AIDS. METHODS: A cross-sectional study was
      undertaken to explore factors influencing the sexual behaviour of high-school
      pupils (mean age 15.4 years; SD 1.11). Structured self-reported questionnaires
      were completed by all grade 10 pupils (N = 805) at all the Wentworth, Durban,
      public high schools. RESULTS: Significant gender differences in sexual practices
      were reported, such as males being more likely to engage in sexual activity than
      females (OR 4.92; p < 0.001). More males (24.8%) initiated sex before age 12,
      compared with more females (30%) who initiated sex between 16 to 20 years of age
      (p < 0.001). Significantly more males preferred older partners than females (p =
      0.002), more females were forced to have sex than males (p = 0.009), and more
      males used alcohol on the last occasion of sex than females (p = 0.04). Religious
      affiliation and parental supervision were found to have a significant effect on
      sexual activity among pupils. CONCLUSIONS: High-school pupils are at high risk of
      HIV and AIDS, yet they continue to engage in risky sexual behaviours. Preventive
      efforts therefore need to be aggressively up-scaled and redirected towards
      specific risky practices, taking gender differences into account. Contextual
      factors such as religious norms and parental supervision also require greater
      attention. Risky sexual behaviours are reflective of a broader crisis in society.

PMID- 18637314
TI  - Immediate loading of implants in the edentulous maxilla.
AB  - The overall aim of this thesis was to investigate different therapeutic
      strategies in treatment of the edentulous maxilla with dental implants and their
      importance for treatment outcome. The introduction of one-stage surgery, in place
      of two-stage surgery, was a paradigm shift in the area of implant treatment since
      submerged implant healing underneath the mucosa was considered a prerequisite for
      healing in the original concept. The advantages of a one-stage method are that a
      second surgery is unnecessary, costs are lower, and patients complain less about
      the surgical procedures. The development of implant treatment, regardless of
      whether it is performed in the mandible or the maxilla, strives to shorten the
      period from implant placement to implant loading. For the edentulous patient--due
      to esthetic, economical, or psychological reasons--shortening this time and thus
      avoiding a long period of wearing a transitional removable prosthesis is
      advantageous. Use of conventional one-stage surgery makes possible and is a
      prerequisite for immediate loading of implants. Successful treatment outcome has
      been demonstrated for immediate loading of implants in the mandible, but
      documentation of the method in the maxilla is still sparse. Two prospective
      clinical studies compared (i) one- and two-stage surgery and (ii) immediate and
      conventional loading in patients consecutively treated in the edentulous maxilla
      with implant-supported fixed prostheses. The first study found that the
      cumulative survival rate (CSR) after one-stage surgery performed according to a
      conventional protocol was consistent with two-stage protocol CSRs reported in
      previous studies. The second study evaluated an immediate loading protocol that
      provided patients with interim fixed prostheses within 24 hours after implant
      placement. A comparison of the studies found no significant difference in CSRs.
      But it was found that when a conventional protocol was used, transitional
      removable prostheses could traumatize the bone-implant interface during healing
      by adverse loading on the implants, which pierced the mucosa. Moreover, splinting
      the implants immediately after surgery with an interim fixed prosthesis might
      protect them from adverse loading. In a finite element analysis comparing
      uncoupled and splinted implants--imitations of the clinical situations in the two
      studies--splinted implants drastically reduced stresses in the bone tissue
      surrounding the implant, which might facilitate bone healing. Two factors
      considered important for a successful treatment outcome, especially when loading
      implants immediately, are (i) jawbone quality and (ii) primary implant stability
      at placement. In implant literature, bone quality is generally equivalent to bone
      density. Results of the third clinical study in this thesis indicate that use of
      computed tomography with calculations of bone mineral density can be a useful
      tool in bone tissue evaluation before implant placement. After 1 year of loading,
      changes in marginal bone level, compared to baseline, did not differ between
      implants that were stable and implants that were not stable at placement. The
      results of this thesis do not strengthen earlier recommendations that immediate
      and early loading is a treatment alternative that can be considered only in jaws
      with good bone quality. In conclusion, immediate loading with interim fixed
      prostheses in the edentulous maxilla is a viable treatment alternative. Splinting
      of implants seems to be important in immediate loading, especially when bone
      density is low.

PMID- 18637315
TI  - On dental caries and caries-related factors in children and teenagers.
AB  - Dental caries is still a common disease among children and adolescents. The aims
      of the present thesis were therefore: 1) to investigate the approximal caries
      prevalence in posterior teeth in 15-year-olds, 2) to study past caries experience
      in the primary dentition in relation to future caries development and need for
      treatment, 3) to investigate factors during early childhood which are associated
      with caries development later in life, and 4) to study the association between
      age-specific body mass index (isoBMI) and approximal caries status in 15-year
      olds. Paper I has a retrospective design and the analyses were based on record
      data from a randomly selected sample. Papers II, III and IV are based on
      radiographic analyses of posterior teeth in 15-year-olds followed longitudinally
      from 1 to 15 years of age. The data for these studies were selected from
      examinations, interviews and questionnaires from early childhood and school
      health care records at 15 years (isoBMI values). The result showed that the
      approximal caries prevalence in 15-year-olds is underestimated in official caries
      data, since initial caries lesions are not included in these statistics. Two
      thirds of all 15-year-olds had approximal caries and initial caries constituted
      86% of the total number of caries lesions. There was a strong relationship
      between caries in early childhood and approximal caries prevalence in the
      posterior teeth at 15 years of age. Children with caries experience at 6 years
      received significantly more treatment in the primary dentition during the period
      from 7 to 12 years compared with children who were caries free at the same age.
      Further, it was pointed out that parents' attitudes to dental health and
      psychosocial factors during early childhood have an effect on approximal caries
      in 15-year-olds. Additionally, plaque on primary incisors at 1 year of age and
      infrequent toothbrushing at 3 years of age were associated with a high caries
      experience at 15 years. It was also demonstrated that adolescents with overweight
      and obesity had a significantly higher approximal caries prevalence than those of
      normal weight. Furthermore, it was shown that children's unfavourable snacking
      habits at 1 and 3 years of age were associated with approximal caries at 15
      years. The main conclusions from this thesis are that: 1) epidemiologicalcaries
      data should include initial caries lesions on approximal tooth surfaces, in order
      to show the actual caries prevalence, 2) there is a strong relationship between
      caries in early childhood and approximal caries prevalence in the posterior teeth
      at 15 years of age, 3) the psychosocial environment in which children live during
      their childhood has an impact on dental health later in life, 4) good oral
      hygiene habits including the use of fluoride toothpaste, established in early
      childhood, provide a foundation for good dental health in adolescence, and 5)
      future preventive programmes should include, at a multidisciplinary level,
      strategies to prevent and reduce both dental caries and obesity at an early age.

PMID- 18637316
TI  - Do we let children's teeth decay just because some people object to topping up
      the natural fluoride that's already in our water?

PMID- 18637317
TI  - Correlates of dental caries in 12-year-old children in Europe: a cross-sectional
      analysis.
AB  - OBJECTIVE: To investigate, from current cross-sectional data, the relationships
      between dental caries experience of 12-year-old children in 29 countries of
      Europe and four independent variables: national wealth (GDP), expressed as
      purchasing power parity (PPP x 1,000US$)/ capita/year; population per active
      dentist; sugar consumption, expressed as Kg/capita/year; and volume sales of
      toothpaste, expressed as litres/capita/year. METHOD: Most of the data were
      abstracted from relevant websites. Information on toothpaste sales was from
      personal communication and obtainable for 16 countries of Western Europe only.
      Relationships were examined using Spearman's rank correlation method. RESULTS:
      Mean DMFT showed a strong negative association with national GDP (rho = -0.729, p
      < 0.01), whilst toothpaste sales showed a statistically significant positive
      association with GDP (rho = 0.599, p < 0.05) as did sugar consumption (rho =
      0.575, p < 0.01). Paradoxically, caries experience yielded a strong negative
      correlation with sugar consumption (rho = -0.561, p < 0.01) such that ranked
      increases in mean DMFT were significantly associated with decreasing levels of
      sugar consumption. None of the other rank correlations was statistically
      significant. CONCLUSIONS: Unavoidable shortcomings of the available data and
      their incompleteness meant that any conclusions that could be drawn were
      speculative. A possible explanation for the anomalous association of low mean
      DMFT with high sugar consumption in Western Europe is that the extensive use of,
      mainly fluoride containing, toothpaste neutralises the potential damage from high
      sugar consumption. Use of sugar principally as a commercial food or drink
      additive in modern times, with potential for buffering of its acidic fermentation
      products, together with a possibly more rapid oral clearance of sugar in additive
      form, may also be a contributory factor.

PMID- 18637318
TI  - Dental caries rates in primary teeth in 2002, and caries surveillance trends 1981
      2002, in a South African city.
AB  - OBJECTIVE: To determine trends in the prevalence and severity of dental caries in
      2- to 5-year-old children. BASIC RESEARCH DESIGN: Repeated cross-sectional
      surveys in 1981, 1983, 1985, 1987, 1989, 1991, 1994, 1997 and 2002. CLINICAL
      SETTING: Nursery schools in Germiston, South Africa. PARTICIPANTS: Dental caries
      was diagnosed by calibrated examiners using WHO criteria in 7,185 2- to 5-year
      old children whose parents had given informed consent. MAIN OUTCOME MEASURES:
      Caries prevalence (%), caries experience (dmft). RESULTS: Both caries prevalence
      and experience showed statistically significant (p < 0.001) fluctuations between
      study years from 1981 to 2002. A worry is an increase in rates between 1997 and
      2002. CONCLUSION: There is a suggestion of a cyclical pattern to the caries rates
      observed.

PMID- 18637319
TI  - Individual and maternal determinants of self-reported dental health among Turkish
      school children aged 10-12 years.
AB  - OBJECTIVE: To assess the influence of maternal and individual characteristics on
      self-reported dental health of Turkish school children aged 10-12 years with
      different socio-economic backgrounds. METHOD: A cross-sectional study of children
      aged 10 to 12 (n = 611) using paired matches of self-administered questionnaires
      for children and their mothers. Clinical examinations based on World Health
      Organization criteria were conduced. The participation rate was 97% (n = 591) for
      the children, 87% (n = 533) for the mothers, and 95% (n = 584) for the clinical
      examinations. Multiple linear regression, descriptive statistics, Spearman
      correlation coefficient and chi-square test were applied. RESULTS: Private school
      children's mothers were more likely to have had higher education (95% at least
      high school) than public school children's mothers (11%); they reported better
      dental health (above average) than did mothers of public school children (p =
      0.001). Among all mothers, those with above average self-reported dental health
      reported more regular dental visits than did those with below average scores (p =
      0.001). Frequency of regular dental visits and toothbrushing among children
      attending public schools (5%, 65%) were lower than those attending private school
      (43%, 79%), (p = 0.001). The mean DMFS was negatively correlated with self
      reported dental health (r(s) = -0.187, p = 0.001). Toothbrushing frequency and
      school performance were the common factors positively associated with self
      reported dental health, among all children. CONCLUSION: The results emphasize the
      important role of mothers and their socio-economic background in enhancement of
      children's dental health. Their active role in conjunction with the potential of
      self-assessment provides a good basis for establishing and improving self-care
      among children, in developing countries in particular.

PMID- 18637320
TI  - Prediction of periodontal pathology around third molars using linear mixed
      effects modeling.
AB  - OBJECTIVE: To compare the random intercept multilevel model with other linear
      mixed effects models in an assessment of the effect of quadrant-, jaw-, and
      person level covariates on probing depth of asymptomatic third molars. BASIC
      RESEARCH DESIGN: Five different covariance models were considered: 1) the random
      intercept multilevel 2) multi-level with unequal jaw variance 3) multi-level with
      unequal tooth variance 4) multi-level with unequal jaw and side variance and 5)
      the general linear model for correlated data with unstructured covariance matrix.
      PARTICIPANTS: 235 subjects with all four third molars erupted were included.
      Fifty-one percent were female and 75% Caucasian. The average age was 29.1 years
      (sd = 7.0). RESULTS: The extended multi-level with unequal residual variance was
      the best fit to the data. Likelihood ratio tests in a stepdown selection approach
      resulted in a final model for mean probing depth that included one statistically
      significant three-way interaction (age x gingival inflammation x gender), two
      statistically significant two-way interactions (jaw x gingival inflammation and
      jaw x gender) and one significant main effect (ethnicity). CONCLUSIONS: Linear
      mixed effects modeling is a powerful tool for the analysis of correlated dental
      data. However, no one covariance structure is appropriate for all purposes.

PMID- 18637321
TI  - Duties and training of dental nurses: how do Irish practices conform to European
      standards?
AB  - AIM: The dental nurse is a key member of the dental team, having an important
      role in the delivery of oral healthcare. Despite this, there is considerable
      variation throughout Europe in relation to the level of training, permitted
      duties, and statutory registration of dental nurses. The purpose of this paper is
      to describe the opinions and attitudes of dental nurses to their roles and
      suitability of training in one European member state, Ireland, where statutory
      registration has recently been introduced. METHOD: A postal questionnaire was
      sent to 150 dental practitioners selected from the Irish Register of Dentists.
      The dentists were asked to distribute questionnaire to dental nurse(s) working in
      their practice. Information sought from the dental nurses included their
      employment setting, the nature of their employment, their level of training,
      additional qualifications held, their views on the key duties and
      responsibilities of a dental nurse, and the appropriate duration and content of a
      dental nurse training programme. RESULTS: Replies were received from 96 dental
      nurses (response rate = 64%). Fifty-five percent of respondents (n = 53) were
      employed in private practice, 39% (n = 37) were employed in the Health Board
      Dental Service, and 6% (n = 6) were employed in a dental hospital. Two thirds of
      respondents (n = 62) had been employed as dental nurses for more than five years.
      Eighty-six percent of respondents (n = 83) were in full-time employment. Seventy
      three percent of respondents (n = 70) held a recognised dental nurse
      qualification. Sixty-five percent of respondents (n = 70) who held a dental nurse
      qualification felt that the appropriate duration of a dental nurse training
      programme was one year or less. Thirty-two percent of respondents (n = 30) had
      completed additional training in practice management, administration or computer
      skills. Ninety-five percent of respondents (n = 91) were interested in attending
      continuing education courses. Eighty-five percent of respondents (n = 82) felt
      that assistance at the administration of local anaesthetics was a key
      duty/responsibility for dental nurses, while only 20% of respondents (n = 19)
      felt that infection control procedures was a key duty. CONCLUSIONS: Within the
      group of dental nurses surveyed, there was a lack of clarity surrounding their
      perception of their key duties. This could present challenges to the effective
      delivery of oral healthcare regimens within Ireland. Further investigation of
      this situation in other European countries is indicated.

PMID- 18637322
TI  - Comparison of ranking dental status using the Significant Caries Index and the
      Significant Filled and Sound-Teeth Index.
AB  - OBJECTIVE: The objective was to test whether the ranking of countries was
      different using the SFS-T (Significant Filled Sound-Teeth Index) or the
      Significant Caries Index (SIC). METHOD: This study compared the country rankings
      using the SiC and the SFS-T indices in 12 year olds in a range of countries. The
      SFS-T is the one-third of the population with the lowest filled or sound teeth
      and is a measure of functional status. We used the SiC and DMFT data from the WHO
      database for 12 year olds. SFS-T index values were estimated for the 12 year olds
      for 16 countries. RESULTS: The ranking by SiC index scores was lower for
      developed countries than for developing countries. CONCLUSIONS: These findings
      suggest that it may be more useful to use the SFS-T index than the SiC index in
      studies comparing dental status between countries.

PMID- 18637323
TI  - Measuring oral health behaviour in Flemish health care workers: an application of
      the theory of planned behaviour.
AB  - OBJECTIVE: This study describes the development and validation of a questionnaire
      to measure the determinants of oral health related behaviour in health care
      workers, based on the Theory of Planned Behaviour (TPB). RESEARCH DESIGN: A
      preliminary questionnaire was drafted containing 78 self report items measuring
      three behaviours related to oral health (i.e. dietary habits, oral hygiene habits
      and dental attendance), as well as the attitudes, perceived social norms and self
      efficacy for each behaviour. The questionnaire was completed by 201 health care
      workers for the initial validation and 966 other health care workers for a
      replication. OUTCOMES: A principal component analysis with Procrustes rotation
      toward an a priori three component structure on the original sample yielded high
      congruence measures for reported dental attendance, but not for dietary habits
      and oral hygiene habits. Subsequent exploratory Varimax rotations and discarding
      of redundant items resulted in three component solutions explaining 43% of the
      variance in dietary habits, 57% in oral hygiene habits and 66% in dental
      attendance, respectively. For all three behaviours, these components corresponded
      to the dimensions of the TPB. Internal consistency of the scales was
      satisfactory, with Chronbach's alpha's ranging from 0.51 to 0.87. Scale scores
      accounted for a significant proportion of the variance in the intention to avoid
      sweet snacks, to brush teeth, and to attend dental check-ups, and of the
      frequency of consumption of sweet drinks and frequency of brushing. A
      confirmatory factor analysis on the larger sample of 966 health care workers
      provided excellent goodness of fit indices, confirming the construct validity of
      the scales.

PMID- 18637324
TI  - The influence of early counselling on weaning from a bottle.
AB  - OBJECTIVES: To evaluate the effectiveness of intensive counselling on bottle
      weaning. METHODS: A randomised prospective controlled study was conducted.
      Parents of 4-month-old babies who attended an inner-city clinic affiliated with
      the Department of Paediatrics, University of Louisville, Louisville, Kentucky
      with predominately African-American, indigent population were invited to
      participate. The parent/infant pairs were randomized to either intervention or
      control groups. Demographic information was recorded and both groups were
      surveyed on the parent's beliefs and knowledge of weaning from the bottle. The
      intervention group parents received scripted counselling, including use of
      feeding cups, and were shown pictures of severe early childhood caries and a
      dental model of early childhood caries at four, six, nine, and 12 month visits.
      Two paediatricians who are on the clinic staff used the same script when talking
      to parents while showing the same photos and dental model to assure symmetry. The
      control group parents received brief counselling on the use of a feeding cup at 6
      month and bottle weaning at nine and 12 months with no photographs or dental
      models shown. Two dentists, blinded to the group assignment, examined all of the
      children between the ages of 12 months and 24 months. RESULTS: One hundred eighty
      five parent/infant pairs were enrolled and 132 pairs (65 control and 67
      intervention) remained at the end of the study. Demographic variables,
      socioeconomic status and race were similar for both groups. When surveyed, more
      of the control mothers believed that children should be weaned by 12 months (p =
      0.049). Yet, only 17% of their infants were weaned by 12 months, compared to 27%
      of the intervention infants (p = 0.168). CONCLUSION: This small study
      demonstrated no change in parental behaviour after intense counselling.

PMID- 18637326
TI  - Orthodontic treatment need in Nigerian children.
AB  - OBJECTIVE: The purpose of this study was to assess the need for orthodontic
      treatment among Nigerian children aged 12-14 years old in Benin City, south
      southern region of Nigeria. RESEARCH DESIGN: The sample consisted of 261 randomly
      selected school children, 122 boys (47%) and 139 girls (53%) with mean age of
      12.9 +/- 0.1. The survey was conducted by clinical examination and both
      components of the Index of Orthodontic Treatment Need (IOTN) were used to
      determine the need for orthodontic treatment. RESULTS: The results revealed that
      50 (19.2%) of the children had a definite need for orthodontic treatment
      according to dental health component while aesthetic component of IOTN indicated
      definite need in 12 (4.6%). Increased overjet, severe contact displacements and
      impeded eruption of teeth were the common occlusal features in the definite
      treatment need group. CONCLUSION: This study provided data on the need for
      orthodontic treatment among Nigerian school children which is useful to plan and
      prioritise orthodontic care and services.

PMID- 18637325
TI  - Prevalence and severity of dental caries in schoolchildren of Porto, Portugal.
AB  - OBJECTIVES: To measure the prevalence and severity of dental caries in
      adolescents of the city of Porto, Portugal, and to assess socioeconomic and
      behavioural covariates of dental caries experience. METHODS: A sample of 700
      thirteen-year-old schoolchildren was examined. Results from the dental
      examination were linked to anthropometric information and to data supplied by two
      structured questionnaires assessing nutritional factors, socio-demographic
      characteristics and behaviour related to health promotion. Dental caries was
      measured using the DMFT index, and two dichotomous outcomes, one assessing the
      prevalence of dental caries (DMFT > 0); the other assessing the prevalence of a
      high level of dental caries (DMFT > or = 4). RESULTS: Consuming soft drinks
      derived from cola (irrespective of sugared or diet) two or more times per week,
      attending a public school, being female and having parents with low educational
      attainment were identified as risk factors both for having dental caries and for
      having a high level of dental caries. CONCLUSION: Caries levels were positively
      associated with frequency of intake of sweetened foods and drinks.

PMID- 18637327
TI  - [Concentrations and influence factors of polycyclic aromatic hydrocarbons in
      leaves of dominant species in the Pearl River Delta, South China].
AB  - Concentrations of PAHs in leaves of six dominant species in the Pearl River Delta
      of South China were determined with gas chromatography and mass spectrometry (GC
      MS), and synchronously leaf-lipid contents, leaf areas, specific leaf areas (SLA)
      were measured. The characters of PAHs abundance and influence factors on them
      were investigated. The results show that concentrations of PAHs in pine needles
      are higher than those in broad-leaves remarkably, and the highest value (1034.7
      ng x g(-1) in Pinus massoniana) is fivefold of the lowest (199.7 ng x g(-1) in
      Schima superba) . Flu, Phe, Fluo, Pyr, Chr are the main components of sigma PAHs,
      and the concentrations of 3-ring and 4-ring PAHs exceed 80% of the total PAHs.
      Significant positive correlations between the components and sigma PAHs were also
      detected. The PAHs contents by per lipid could reduce inter-species variance
      obviously, and the diversity is no more than two times (6.8 ng x mg(-1) and 2.7
      ng x mg(-1), respectively). Adversely, the PAHs contents by per cm2 magnify inter
      species variance, and the highest value (15.3 ng x cm(-2)) ascends to eight times
      of the lowest (1.9 ng x cm(-2)). Furthermore, significant positive correlation
      between PAHs and leaf-lipid contents was identified, as well as negative
      correlation between PAHs and specific leaf areas. All of these indicate that leaf
      lipid contents and specific leaf areas are two significant factors which
      influenced PAHs contents in leaves.

PMID- 18637328
TI  - [Oxidative damages of long-term exposure to low level fullerenes (C60) in
      Carassius auratus].
AB  - To determine the potential effects of fullerenes (C60) on aquatic organism,
      larval Carassius auratus was exposed to low level C60 (0.04-1.0 mg x L(-1)) for
      32 days. Then the oxidative damages in brain, liver and gill tissue of larval
      Carassius auratus were measured. The results showed that: compared to the
      control, the reduced glutathione (GSH) contents in all different tissues
      decreased significantly (p < 0.05), and the most serious inhibition of GSH with a
      14.3% inhibition rate was found in the gill tissue of larval crucian exposed to 1
      mg x L(-1) C60 aqueous suspension; whereas the superoxide dismutase (SOD) and
      catalase (CAT) activities in liver tissue, Na+ -K+ -ATPase activities in gill
      tissue were stimulated significantly (p < 0.05), and the maximal activity of them
      were 121.34% (exposed to 0.04 mg x L(-1) C60 aqueous suspension), 114.80%
      (exposed to 0.04 mg x L(-1) C60 aqueous suspension) and 348.59% (exposed to 0.20
      mg x L(-1) C60 aqueous suspension) respectively than that of control. The
      experiment results indicated that oxidative damages induced by long-term exposure
      might play a role in the bio-toxicity of C60 to larval crucian.

PMID- 18637329
TI  - [Effects of arsenic from soil and irrigation-water on As accumulation on the root
      surfaces and in mature rice plants (Oryza sativa L.)].
AB  - A compartmented soil-glass bead culture system was used to investigate
      characteristics of arsenic accumulation in iron plaque and in mature rice plants
      irrigated using water with arsenic in greenhouse. Arsenic was supplied as a
      solution of Na3AsO4 * 12H2O at the following stages: tillering, stem elongation,
      booting, flowering and grain filling. The whole plant was separated into four
      parts and As concentrations were analyzed in DCB (dithionite-citrate-bicarbonate)
      extraction, root, straw, rice husk and grain respectively. The results show that
      irrigation-water with arsenic has no significant effect on biomass of straw and
      grain. Arsenic concentrations are distributed in different components of mature
      rice with the ranking of iron plaque > root > straw > husk > grain. Arsenic in
      straw and grain just derive from soil in control, and derive from soil and
      irrigation-water in arsenic treatment. About 76.5% and 71.0% of total arsenic in
      rice straw are from soil for lines of YY-1 and 94D-64 respectively. There is no
      significant difference between two lines. However, about 33.6% of total arsenic
      in grain of YY-1 comes from irrigation-water with arsenic, and only 15.2% of
      total arsenic in grain of 94D1-64 is from irrigation-water with arsenic. There is
      a significant difference between YY-1 and 94D-64. Arsenic concentrations in rice
      grain are lower than the food safety limitation in China (0.7 mg x kg(-1)).

PMID- 18637330
TI  - [Degradation of nonylphenol and short chain nonylphenol polyethoxylates in soil].
AB  - Biodegradation of nonylphenolic estrogens in soil and sludge-amended soil were
      investigated. Biodegradations of nonylphenol (NP), nonylphenol monoethoxylate
      (NPEO1) and nonylphenol diethoxylates (NPEO2) followed the first-order kinetics,
      and the degradation rates were enhanced when the temperature was increased.
      Spiked NP, NPEO1 and NPEO2 (with the concentration of 100, 50 and 100 mg x kg(
      1), respectively) could be degraded completely in 45 days at the temperature of
      30 degrees C. NP presented a higher degradation rates in soil than NPEO1 and
      NPEO2 under the same condition. The amended sludge enhanced the biodegradation of
      NPEO1 and NPEO2 in soil, while it inhibited that of NP.

PMID- 18637331
TI  - [Pollutant loading analyses and TP model calculation for eutrophication in Lichee
      Lake in Shenzhen].
AB  - Based on 9-month consecutive in situ monitoring data, this paper investigated the
      pollutant sources and loadings of eutrophication in Lichee Lake in Shenzhen. The
      external source mainly comes from overflow of storm sewer system, which will
      deteriorate water quality in lake. Total phosphorus concentration was measured
      with a maximum of 0.347 mg/L after overflow. The sediment release experiment
      showed that the release rate of total nitrogen during the first week was about
      0.036 8 g/(m2 x d), and less release of total phosphorus from sediment into water
      was measured under aerobic condition. The total phosphorus modeling of each sub
      lake for Lichee Lake was developed. The model had a good agreement with 2 groups
      of monitoring data. And calculation results showed that, it will take 2.18 days
      subject to 24-hour operations of the integrated treatment project per day to
      improve water quality in Lake to satisfy the National Standard IV of surface
      water.

PMID- 18637332
TI  - [Treatment effect of eutrophication restoration project for Lichee Lake in
      Shenzhen].
AB  - Based on 9-month monitoring field data, this paper analyzes the variation of
      chlorophyll-a (Chl-a), total phosphorus (TP), total nitrogen (TN) and
      transparency (SD) in different sub-lake districts in order to study the treatment
      effect of eutrophication restoration project in Lichee Lake in Shenzhen. The
      statistical results show that, the average of TP and TN for whole lake were below
      0.1 mg x L(-1) and 1.5 mg x L(-1) respectively, the average of Chl-a of north
      lake district and east lake district were 16.77 microg x L(-1) and 21.45 microg x
      L(-1) respectively, lower than that of south lake district (35.83 microg x L(-1)
      and west lake district (32.69 microg x L(-1)), and the average of SD for whole
      lake was greater than 0.5 m. During the 9-month operation of the restoration
      project, the average water quality satisfied the National Standard IV for surface
      water and the water was improved from hypereutrophic status to eutrophic status
      in Lake.

PMID- 18637333
TI  - [Numerical simulation on hydrodynamic character for algae growth].
AB  - In order to quantificationally study the direct effects of hydrodynamic condition
      on the growth of algae, the Microcystis aeruginosa was chosen to carry through
      the disturbance-experiment. By keeping the same value of illumination,
      temperature and nutrition and changing the rotate speed of oscillator, the
      growing processes of algae under different disturbance intensities were
      researched. The hydraulic parameter was presented to amend the formula for the
      growth of algae. Take Neijiang as an example. A 2-D unsteady model for algae
      growth was established to forecast the scope of water blooms in Neijiang. It is
      found that the growth of algae is obviously influenced by hydrodynamic condition,
      and a condign low velocity is beneficial for its growth while both the quiescence
      condition and high velocity will restrain its growth rate. After the close of the
      water gate in Leading Channel, the velocity in Neijiang will be decreased, which
      accelerated the growth rate of algae, and the area of water blooms will be
      increased to 2.5 km2 which is about 36.8 percent of the total water surface area
      of Neijiang. Under the quiescent condition and the improved hydrodynamic
      condition, the growth rate of algae will be effectively controlled and the area
      of water blooms will be reduced to 0.78 km2 and 0.18 km2 respectively.

PMID- 18637334
TI  - [Purification effects on nitrogen under different concentration and nitrogen
      conformation transform principles by Vallisneria spiraslis L].
AB  - Wet vegetation performed different physiological actions under different
      pollution loads, thus inducing different purification effects on pollutants.
      Since water of various rivers, lakes and ponds are polluted at different extents
      and purification levels currently in China, a typical submerged vegetation,
      Vallisneria spiraslis L. is selected to study the purification effects on total
      nitrogen(TN) under different purification levels, which is widely distributed in
      rivers and lakes of Yangtz middle and down stream. The targets of this paper are
      to determine the nitrogen degradation impacts of Vallisneria spiraslis L., and
      nitrogen accumulation and distribution in leaf and root rules, and inorganic
      nitrogen conformation transformation characters under 7 nitrogen loads during 7
      to 22 Sept., 2006. The 7 nitrogen loads are 1.0 mg/L, 5.0 mg/L, 10.0 mg/L, 20.0
      mg/L, 40.0 mg/L, 60.0 mg/L and 80.0 mg/L. The experiment data show that
      Vallisneria spiraslis L. have significant effects on nitrogen purification while
      the TN concentration equal to and less than 60 mg/L, and the contribution
      principles of vegetation are similar among the 6 loads. Whereas, when the TN load
      bigger than 80.0 mg/L, Vallisneria spiraslis L. have no obvious contribution on
      nitrogen purification. Meanwhile, the nitrogen accumulation principles in the
      leaf and root of Vallisneria spiraslis L. is interrelated to the TN load.
      However, its distribution ratio in leaf to root is unrelated with TN load.
      Furthermore, the conformation of inorganic nitrogen transform characters changed
      with the TN load increasing. It is concluded that ammonia concentration decreased
      rapidly while the nitrogen load less than 20.0 mg/L, and the ammonia
      concentration ratio in the inorganic nitrogen increased remarkably with the
      nitrogen load increasing. Results indicate Vallisneria spiraslis L. have
      different purification contribution extents which can be benefit for nitrogen
      removal in different eutrophicated water and wet vegetation restoration.

PMID- 18637335
TI  - [Effect of intermittent artificial aeration on nitrogen and phosphorus removal in
      subsurface vertical-flow constructed wetlands].
AB  - Shale and T. latifolia were used as subsurface vertical-flow constructed wetland
      substrate and vegetation for eutrophic Jin River water treatment, and investigate
      the effect of intermittent aeration on nitrogen and phosphorus removal. In this
      study, hydraulic loading rate was equal to 800 mm/d, and ratio of air and water
      was 5:1. During the entire running period, maximal monthly mean ammonia-nitrogen
      (NH4+ -N), total nitrogen (TN), soluble reactive phosphorus (SRP) and total
      phosphorus (TP) removal rates were observed in August 2006. In contrast to the
      non-aerated wetland, aeration enhanced ammonia-nitrogen, total nitrogen, soluble
      reactive phosphorus and total phosphorus removal: 10.1%, 4.7%, 10.2% and 8.8% for
      aeration in the middle, and 25.1%, 10.0%, 7.7% and 7.4% for aeration at the
      bottom of the substrate, respectively. However, aeration failed to improve the
      nitrate-nitrogen removal. During the whole experimental period, monthly mean NO3(
      ) -N removal rates were much lower for aerated constructed wetlands (regarding
      aeration in the middle and at the bottom) than those for non-aerated system.
      After finishing the experiment, aboveground plant biomass (stems and leaves) of
      T. latifolia was harvested, and its weight and nutrient content (total nitrogen
      and total phosphorus) were measured. Analysis of aboveground plant biomass
      indicated that intermittent aeration restrained the increase in biomass but
      stimulated assimilation of nitrogen and phosphorus into stems and leaves.
      Additional total nitrogen removal of 11.6 g x m(-2) and 12.6 g x m(-2) by
      aboveground T. latifolia biomass for intermittent artificial aeration in the
      middle and at the bottom of the wetland substrate, respectively, was observed.

PMID- 18637336
TI  - [Source and fluctuation of trace geosmin and 2-MIB in drinking water of
      Shanghai].
AB  - Liquid-liquid microextraction/GC/MS analysis method was employed in detecting
      trace odorants in drinking water. A-year-long investigation on odor chemicals was
      carried out in source water and drinking water in a certain waterworks of
      Shanghai. The results showed that 2-MIB was the main contaminant which induce
      disgusting odor to drinking water of Shanghai in July, August, September and
      October in a year with the peak concentration of 2-MIB 152.82 ng/L in raw water
      and 97.94 ng/L in finished water from waterworks. Oscillatoria was suspected as
      the resource of 2-MIB.

PMID- 18637337
TI  - [Non-nitrification pathway for NH4+ -N removal in pilot-scale drinking water
      biological processes].
AB  - The non-nitrification pathway for NH4+ -N removal in pilot-scale drinking water
      biological treatment processes and its possible mechanism were investigated
      through calculating N and DO stoichiometric balance. With more than 2 mg/L NH4+ 
      N in the influent, for the fluidized bed bioreactor (FBBR), the total of NH4+ -N,
      NO2(-) -N, NO3(-) -N in the influent was 0.91 mg/L higher than that in the
      effluent, and for the biofilter, its DO consumption was 2.90 mg/L less than the
      stoichiometric amount. The results suggested that nitrogen loss occurred in both
      reactors and a part of NH4+ -N was removed through non-nitrification pathway.
      Because the utilization of phosphorus and organic matters was independent of
      nitrogen loss, the assimilation and denitrification could be excluded from the
      possible mechanisms. Because the very low C/N in the influent and the
      accumulation of NO2(-) -N in the reactors were similar with the wastewater
      biological processes, the "autotrophic removal of nitrogen" was regarded as the
      most probable non-nitrification pathway. In this mechanism, the couple of short
      cut nitrification and ANAMMOX (or OLAND) leading to the transformation of NH4+ -N
      and NO2(-) -N into gaseous N2 was responsible for the nitrogen loss in drinking
      water biological processes.

PMID- 18637338
TI  - [Pilot study on combined MBR-RO process for wastewater recovery].
AB  - The combined MBR-RO pilot system, using A2/O-MBR technology as a pre-treatment
      process, has been set up for the direct municipal wastewater treatment and
      recovery. The objective of this pilot study was to further investigate the
      feasibility of MBR system as a pretreatment process for RO permeation, estimate
      the MBR-RO process to produce high grade effluent, and evaluate the different pre
      conditions affecting the RO permeability and bio-fouling. The results showed that
      the average RO permeate qualities were as TOC < 1.3 mg/L, NH4+ -N < 0.03 mg/L, TN
      < 0.1 mg/L and not detectable for TP, in terms of conductivity < 30 microS/cm and
      turbidity < 0.12 NTU, and complete inorganic irons rejection could be achieved
      with the lowest concentration, thus the grade of RO effluent could meet the
      drinking water standard. MBR technology was suitable as a pre-treatment process
      for RO in the MBR-RO process and thus no severe RO bio-fouling occurred during
      the whole study period of 6 months.

PMID- 18637339
TI  - [Solubilization of nitrobenzene in micellar solutions of Tween 80 and inorganic
      salts].
AB  - The solubilization of nitrobenzene by a nonionic surfactant Tween 80 was
      investigated at 10 degrees C. Experimental results indicated that the solubility
      of nitrobenzene in water was greatly enhanced by Tween 80 at surfactant
      concentration above CMC(critical micelle concentration) and a linear relationship
      was obtained between surfactant concentration and nitrobenzene concentration from
      the solubility curve. The molar solubilization ratio (MSR) value was 5.093 and
      IgKm was 3.499. The solubilization was attributed to the ethoxylation group in
      Tween 80 micellar. Effect of four inorganic salts such as NaCl, KCl, CaCl2 ,
      MgCl2 on water solubilities of nitrobenzene in Tween 80 micellar solutions was
      also investigated by a matrix of batch experiments. Mix the Tween 80-inorganic
      salts at the total mass ratios of 2:1, 5:1 and 10:1. The results show that the
      inorganic salts at a high concentration( > or = 500 mg x L(-1)) can enhance the
      solubilization capacities of Tween 80 micellar solution and increase the value of
      MSR and IgKm . Because of the salting-out effect between the micellar of Tween 80
      and inorganic salts, the volume of micelle turns bigger, which may provide larger
      solubility volume for nitrobenzene. The mixture of nonionic surfactant and
      inorganic salts can be used in subsurface remediation as a flushing solution.

PMID- 18637340
TI  - [Effect of chlorination on the structure of dissolved organic matters in
      secondary effluent].
AB  - Dissolved organic matter in the secondary effluent from the W wastewater
      treatment plant (Harbin) was fractionated using XAD resins into five fractions:
      hydrophobic acid (HPO-A), hydrophobic neutral (HPO-N), transphilic acid (TPI-A),
      transphilic neutral (TPI-N) and hydrophilic fraction (HPI). The distribution,
      trihalomethane formation potential (THMFP), UV-Vis and FTIR spectra of organic
      fractions in the secondary effluent were examined. XAD fractionation results
      showed that HPO-A and HPI dominated in the secondary effluent, collectively
      accounting for about 70.8%. HPO-A was the main precursors for THMFP following
      chlorination. HPO-A had the highest specific THMFP (STHMFP) and averaged 232.9
      microg/mg. The STHMFP of HPO-N, TPI-A, TPI-N and HPI ranged from 100 microg/mg to
      125 microg/mg. Chlorination resulted in increased UV-Vis absorbance for TPI-N and
      decreased UV-Vis absorbance for HPO-A, HPO-N, TPI-A and HPI. After chlorination,
      O--H, C=C and aromatic ring were found to decrease while C--O was observed to
      increase for HPO-A, HPO-N, TPI-A and TPI-N. In addition,C=O and C--Cl were found
      to occur as by-products from the chlorination reaction.

PMID- 18637341
TI  - [Partial nitrification in SBR under normal temperature and limited oxygen
      condition].
AB  - Partial nitrification was researched in a SBR reactor under the limited oxygen
      condition (DO 0.3-0.4 mg/L) and the normal temperature of 14.1-24.2 degrees C to
      produce the correct influent for ANAMMOX process from secondary wastewater (NH4+ 
      N 30-100 mg/L). The influent for the ANAMMOX process must be composed of NH4+ and
      NO2- in a ratio of 1/1.31 and therefore only a partial nitrification of ammonium
      into nitrite was required. The control of alkalinity and the indication of
      monitoring profile of DO allowed to achieve this partial nitrification with a
      final effluent only composed of NH4+ -N and NO2(-) -N at the right stoichiometric
      ratio. The equal consumption of HCO3- /NH4+ in secondary wastewater resulted in a
      natural pH decrease when approximately 57% of NH4+ -N was oxidized. When the pH
      dropped to a certain level, the lowering of the metabolic rate of the ammonium
      oxidizer would lead to rapid decline of the oxygen uptake rate (OUR) in reactor,
      and the jump characteristic point (it was distinguished by the jump over 1.0 mg/L
      of DO value) in the DO profile would emerge, which signalled the end-point of the
      partial nitrifying. The optimum alkalinity of partial nitrification was studied
      under 4 concentrations in the range of NH4+ -N 30-100 mg/L of secondary
      wastewater. The result indicated that the bicarbonate/ammonium ratio was the key
      factor influencing the nitrification ratio (NO2-/NH4+), and it was absolutely
      possible to successfully achieve partial nitrification that provided right
      substrate for ANAMMOX reactor through the control of the alkalinity.

PMID- 18637342
TI  - [Biological nitrogen and phosphorus removal in the anaerobic-aerobic-anoxic
      aerobic-anoxic-aerobic sequencing batch reactors].
AB  - The biological nitrogen and phosphorus removal was investigated in two anaerobic
      anoxic-aerobic sequencing batch reactors (SBRs), which were fed with synthetic
      and municipal wastewater, respectively. The operating cycle of (AO)3 SBR was 1.5
      h anaerobic --> 1 h aerobic --> 1 h anoxic -->20 min aerobic --> l h anoxic -->
      20 min aerobic. The removal efficiency of COD, total nitrogen and total
      phosphorus for synthetic wastewater was 88%, 89%, 99%, respectively, while it was
      85%, 75% , 99.5% for municipal wastewater. Furthermore, it was observed that
      though there were much differences in polyhydroxyalkanoates (PHAs) accumulation
      and phosphorous release in the anaerobic stage between two SBRs, the ratio of the
      anoxic energy production efficiency to the aerobic one was close to each other
      (49% versus 50%).

PMID- 18637343
TI  - [Effect of cathode material on electrolytic treatment of Acid Orange 7 by a three
      phase three-dimensional electrode reactor].
AB  - The simulative wastewater containing Acid Orange 7 (AO7) of 300 mg/L was
      electrolytically treated by a three-phase three-dimensional electrode reactor.
      Particular attention was paid on the comparison of treatment efficiency of
      different cathodes in the system. Intermediate products and concentration of *OH
      and H2O2 were further investigated using HPLC, UV-Vis scan and GC-MS, with the
      purpose of investigating the electrolysis behavior of AO7 with different
      cathodes. Results showed that activated carbon fiber (ACF) cathode was more
      effective than graphite or stainless steel cathode. Despite all of the three
      investigated cathodes showed high efficiency in the decolorization of AO7 (more
      than 96% after 60 min of electrolysis under 20 V), the TOC removal ratio of ACF
      system (57.4%) was much higher than those of the other two. Although the
      generation of *OH and H2O2 were both found in the three systems, the
      concentration in the system with ACF as the cathode was much higher than those in
      the other two, which resulted in the better mineralization ability. Moreover, the
      same degradation route of AO7 was found in the three systems, which involved the
      generation of ketone and naphthol compounds.

PMID- 18637344
TI  - [Competitive adsorption between bromine and bromate on activated carbon and
      impact on bromate formation].
AB  - Regularity of adsorption removal for bromine and bromate in water has been tested
      by three different activated carbon. It is demonstrated that in single adsorbent
      solution adsorption removal rates for bromine and bromate is 69% and 88%,
      respectively. As for double adsorbent solution, the removal rate of bromine
      decreased to 10% and of bromate is higher than 60%. The competitive adsorption
      between NOM and bormate is due to surface area and pore size distribution etc.
      The pore size distribution for AC-400 favors NOM adsorption process but hinders
      bromate adsorption. In low concentration solution(c(e) < 72 mg x L(-1)) NOM is
      absorbed with high rate, while in the solution with the concentration between 72
      mg x L(-1) and 211 mg x L(-1), AC-150 is effective in removing NOM. Furthermore,
      ammonia concentration and pH level has impact on bromate removal rate in water.
      The optimal conditions for bromate removal are determined by ammonia
      concentration less than 200 microg/L and low pH in water.

PMID- 18637345
TI  - [Flocculation of kaolin suspensions by chitosan grafted ternary polymerization
      flocculant].
AB  - Flocculation of kaolin suspensions using ternary polymerization flocculant (CAS)
      synthesized by chitosan (CTS), acrylamide and ethyl acrylate quaternary ammonium
      salt was investigated in lab-scale. It was found that CAS had more advantages
      such as higher flocculation efficiency, lesser dosage and wider pH flocculation
      range than CTS. CAS was insignificantly exposed to the properties of suspended
      particles, so preferable flocculation efficiency by it could be obtained both
      with distilled water and tap water kaolin suspensions. The optimal dosage for CAS
      was only one-tenth of that of CTS in neutral condition. Good flocculation
      performance was observed in the pH range of 2.0-11.0 at the dosage of 0.5 mg x L(
      1) CAS, and the turbidity removal rates were about 95%. It was also shown that
      flocculation efficiency was very sensitive to the raw turbidity of kaolin
      suspensions. At less than 0.5 mg x L(-1) of CAS dose, the higher raw turbidity of
      the suspension contrarily yielded a lower removing rate. However, when the dosage
      of CAS was more than 0.5 mg x L(-1), the flocculation efficiency increased with
      increasing the raw turbidity of kaolin. When the dosage was more than 1.0 mg x L(
      1), turbidity removal efficiencies exceeding 85% could be achieved in overall
      experimental turbidities from 10 to 160 NTU. iPDA-100 device was used to follow
      the particle aggregation process. And also zeta potential values of
      particles,floc sizes, shape analyses were presented. It is presumed that the
      flocculation induced by CAS is dominated by charge patch mechanism and bond
      bridging. The flocculation reactivity of kaolin suspensions exhibits a dynamic
      changing, which is simultaneously responsible for several kinds of driving
      forces.

PMID- 18637346
TI  - [Preparation and characterization of cross-linked polyvinyl alcohol microspheres
      as a novel precoating reagent in dynamic membrane].
AB  - In order to modify the membrane surface by adsorbing a precoated layer, cross
      linked polyvinyl alcohol microspheres were prepared via an emulsion
      polymerization that PVA cross linked with glutaraldehyde which was extracted by
      anhydrous aether. Effects of concentration of PVA solution, the volume ratio of
      aqueous phase to oil phase, the selection of surface active agent (SAA) and its
      concentration on the stabilization of emulsion were studied. When the
      concentration of PVA solution was 2.7%, the volume ratio of PVA solution/n
      heptane was 40:60 and the concentration of span-80 was 1.30 g/dL, the prepared
      microspheres contented our needs. The size of microspheres diminished with the
      stirring speed increasing under the condition of enough span-80. It became
      smaller with the accretion of an aimed cross-linking degree which has little
      affection on surface charge. The contact angle of PVA microspheres with distilled
      water showed that these microspheres were hydrophilic. Morphology of PVA
      microspheres were observed by SEM. The FTIR results suggested that functional
      groups varied with the change of aimed cross-linking degrees.

PMID- 18637347
TI  - [Treatment of oil-manufacturing wastewater by yeast-SBR system].
AB  - Eight yeast strains were applied to a sequencing batch reactor (SBR) to treat
      high-strength oil-containing wastewater. The removal performance, yeast
      cultivation method and key factors affecting the stability of system were
      discussed. The results show yeast sludge with MLSS of 19 g/L and SVI of 35 mL/g
      can be obtained in 6 d in an open system without any molds and bacteria inhibitor
      addition; In 30 d continuous wastewater treatment, COD and oil removal rate
      achieve 86.8%-96.9% and above 99.5% respectively under the influent conditions of
      the COD of 9000-23000 mg/L and oil of 4500-16000 mg/L; Short period of pH impact
      brings reversible effects on the system and the sludge retention time can affect
      the SVI of the yeast; Absence of nitrogen induces morphology conversion of some
      yeast cells from single cell to filamentous one and impairs the settling
      capability of the yeast.

PMID- 18637348
TI  - [Oxidation kinetics of pentachlorophenol by manganese dioxide].
AB  - Experiments were conducted to determine oxidation kinetics of pentachlorophenol
      (PCP) using manganese dioxide (MnO2) as an oxidant. The influence of cosolutes
      (e.g. inorganic ions and organic substances) on the reaction kinetics was also
      assessed. When simulating the kinetics of PCP with n-order reaction model by a
      non-linear curve fitting approach, the reaction order n is over 0.999, which
      suggests that the first order reaction model fit the degradation kinetics of PCP.
      The apparent rate constant k(obs) values are 2.86 h(-1) for the centrifugation
      method and 2.14 h(-1) for the ascorbic acid method by non-linear fitting the
      kinetics of PCP for 0.5 h reaction using pseudo-first-order model under the 95%
      confidence limits. The addition of bivalent metal ions causes the considerable
      reduction of the apparent rate constants. The significant effect on the k(obs) of
      PCP occurs when the concentration of Mn2+ above 2% of the initial MnO2 is added
      as the co-solute, but no significant influence on the k(obs) of PCP for the
      presence of other ions. The presence of caffeic acid, syringic acid or gallic
      acid reduces the reaction rate of PCP significantly. Oppositely, no considerable
      decrease of k(obs) is observed in experiments with the addition of cinnamonic
      acid, coumaric acid, ferulic acid or ortho (para)-hydroxybenzoic acid. These
      experimental results demonstrate that the decrease of PCP adsorbed to MnO2
      considerably or the action of competing against PCP reacted with MnO2 is the
      dominant factor that slows down the transformed rate of PCP oxidation by MnO2.

PMID- 18637349
TI  - [Dechlorination mechanisms of chlorinated hydrocarbons by supported nanoscale
      Pd/Fe].
AB  - Some volatile chlorinated hydrocarbons such as VC, 1,1-DCE, TCE, PCE, gamma-HCH,
      were dechlorinated by synthesized supported nanoscale Pd/Fe. The dechlorination
      reactions of PCE, TCE, 1,1-DCE, VC, gamma-HCH follow the pseudo-frist order
      kinetics equations with the k(obs) of 2.79 h(-1), 2.35 h(-1), 1.12 h(-1), 2.14 h(
      1) and 4.02 h(-1) respectively. Little or no medial products were detected and
      the main end products were C2H6 and C2H4 during the dechlorination of VC, 1,1
      DCE, TCE, PCE. The total carbon ratio of C2H6 and C2H4 were 70% and 10%
      respectively during the dechlorination of TCE. The supported nanoscale Pd/Fe
      particles after exposed to air for 24 h were used for 8 cycle experiments and the
      results indicate that the particles have favorable stability. The reactivity has
      no obvious decrease after 200 hours' successive dechlorination experiments of
      gamma-HCH which indicates that the particles represent good durability. The
      reaction activation energy of all the chlorinated hydrocarbons are bigger than 29
      kJ x mol(-1) which shows that the surface-chemical reaction rather than diffusion
      is the rate-limiting step in the metal-mediated dechlorination process. A
      consistence between the experimental data and simulated curves indicates that the
      muti-step reaction pathways proposed offer a better explanation of the reaction
      mechanisms than sequential hydrogenolysis reactions in the transformation of
      chlorinated hydrocarbons by supported nanoscale Pd/Fe.

PMID- 18637350
TI  - [Treatment of dichlorvos by ozone oxidation].
AB  - The dichlorvos of organophosphates was oxidized by ozone in a reactor of 12 L,
      when its initial concentrations was 30 mg/L, ozone concentrations was 4.9, 6.7
      and 7.6 mg/L, pH was 3.1, 5.3, 7.2, 9.4, 11.2 and temperature was 10-50 degrees
      C, and the reaction kinetics of the treatment of dichlorvos by ozone were
      discussed. The results show that ozonation is an efficient way for treating
      dichlorvos. The removals of dichlorvos are all over 96% in 5 min ozonation. When
      ozone concentration is 6.7 mg/L, mineralization rate in TOC reaches 34.8% in 4
      min. The degradation rate of dichlorvos increases as the ozone concentration
      increases but descends as its initial concentration increases. The removal effect
      of dichlorvos is roughly independent of pH value and temperature. When ozone
      concentration is 6.7 mg/L at pH 7.2 in room temperature, the ozonation reaction
      order of dichlorvos is about 0.11 and the reaction rate constant is 7.72 mg x (L
      x min)(-1).

PMID- 18637351
TI  - [Performance and microbial characteristics of an EGSB reactor treating brewery
      wastewater under 20 degrees C].
AB  - A lab-scale EGSB reactor fed by artificial brewery wastewater was operated under
      20 degrees C continuously, and its process performance, characteristics of
      granular sludge, microbial community structure were investigated. The results
      indicated that: 1) after 184 days' operation, the organic loading rate of EGSB
      reactor could reach 10 kg/(m3 x d) at HRT of about 18 h, the COD removal
      efficiencies were above 85%, and the specific biogas production was about 0.58 m3
      per kilogram COD removed. 2) As the organic loading rate increased, the average
      diameter of the granule increased, and the settling velocity increased too, but
      when the loading rate reached about 10 kg/(m3 x d), the granular average diameter
      decreased slightly. Compared with the granular sludge operated at mesophilic
      condition, the ECP contents especially the protein contents in the granular
      sludge operated at 20 degrees C increased obviously. 3) Compared with the seed
      sludge, the main Archaea (methanogenes) species in the sludge samples operated at
      different loading rates under 20 degrees C did not change greatly, but the
      dominant methanogenes in the sludge operated under 15 degrees C for 6 months
      seeded with the same mesophilic sludge changed obviously.

PMID- 18637352
TI  - [Bio-hydrogen production from different pretreated sludge by Pseudomonas sp. GL1
      and changes in the liquid phases].
AB  - Batch tests of anaerobic fermentative hydrogen production by Pseudomonas sp. GL1
      were investigated using sterilization, microwave and ultrasonication pretreated
      sludge as substrate. The profiles of soluble COD, protein, carbohydrate and pH
      value during the fermentation process were monitored. The results showed that
      only hydrogen and carbon dioxide were produced and methane was not observed
      during the process. A maximal hydrogen yield (30.07 mL x g(-1)) and bio-hydrogen
      content (81.45%) were obtained from the sterilization pretreated sludge run. The
      shortest lag time for hydrogen production was in ultrasonication pretreated
      sludge run (3 h), while the longest one was in sterilization pretreated sludge
      run (15 h), and the medial one was in microwave pretreated sludge run (12 h). It
      was found that the changes of sludge substrates (soluble COD, protein,
      carbohydrate and pH value) were various with different pretreated sludge during
      the fermentation process, especially in the sterilization sludge run, which
      implied that the pretreatment method could affect substrate utilization by
      Pseudomonas sp. GL1.

PMID- 18637353
TI  - [Effect of alkaline and ultrasonic pretreatment on the sludge disintegration].
AB  - In order to enhance the efficiency of anaerobic digestion, the effects of
      ultrasonic pretreatment, alkaline pretreatment and the combination of these two
      methods have been studied on sludge disintegration by using multifrequency
      ultrasonic batch. The results showed that the combining of ultrasonic and
      alkaline treatment was more effective than alkaline or ultrasonic treatment alone
      in releasing SCOD and VSS solubilization. The VSS reduction rate was 15.98% with
      ultrasonic pretreatment alone, 22.12% with alkaline pretreatment alone(NaOH/TS =
      0.04). When the sludge was pretreated by the alkaline treatment (NaOH/TS = 0.04)
      for 24 h followed by ultrasonic vibration for 60 min, and simultaneous ultrasonic
      (60 min) and alkaline( NaOH/TS = 0.04) treatment, the VSS reduction rate could
      reach 51.45% and 54.45% respectively. Two distinct phases of hydrolysis were
      observed. The first phase was a very rapid increase in solubilization, followed
      by a much slower second phase. According to kinetic analysis for first rapid
      phase, the simultaneous alkaline and ultrasonic treatment could not only get the
      highest hydrolysis rate among these methods, but also reduce the pretreatment
      time in ultrasonic pretreatment and alkaline dose in alkaline treatment.

PMID- 18637354
TI  - [Relationships between stable isotopes in precipitation in Wolong and monsoon
      activity].
AB  - Stable isotopic analyses with precipitation, air temperature, wind direction and
      wind speed were performed in the Wolong Nature Reserve from July, 2003 to July,
      2004. Results showed that d-excess values were (8.4 +/- 7.4) per thousand, (- 7.4
      +/- 12.5) per thousand and (12.5 +/- 12.1) per thousand in precipitation events
      from April to August, September to October and November to March, respectively.
      Stable isotopic characteristics and d-excess values indicated that precipitation
      was mainly brought by the East Asia monsoon from ocean surface moisture from
      April to August, by the Indian summer monsoon from ocean moisture which extremely
      affected by rainout (strong depletion of heavy isotope) from September to
      October, and by Westerly from inland evaporation and local evaporation from
      November to March. Significant negative correlations between isotopic values and
      precipitation, which was amount effect, were found from April to October (r = -
      0.389 for deltaD and r = - 0.380 for delta18O, p < 0.05, respectively) .
      Temperature effect also might affect isotopic values in precipitation (p < or =
      0.10). During the active period of the East Asia monsoon and the Indian summer
      monsoon, stable isotopes in precipitation events had significant negative
      correlations with south wind index (r = - 0.354 for deltaD and r = - 0.390 for
      delta18O, p < 0.05, respectively), indicating that isotopic values closely
      associated with the origin and transport of moisture, and especially the Indian
      summer monsoon could bring vapors with very low isotopic values and d-excess
      values.

PMID- 18637355
TI  - [Chemical characteristics of atmospheric precipitation in Shenzhen].
AB  - The precipitation chemical components are good indicators of the air pollution.
      With rapid economic developing, air quality has greatly changed in Shenzhen. To
      investigate Chemical feature of precipitation and atmospheric pollution
      characteristics in Shenzhen, two-year precipitation samples in Shenzhen were
      collected and analyzed. Based on the dataset, chemical characteristics of
      rainwater in Shenzhen were discussed. Results show that the concentration of the
      sum of anions and rations in Shenzhen rainwater was lower compared to northern
      cities like Beijing, whereas the acidification of rainwater was very serious in
      Shenzhen. Volume-weighted mean pH values of rainwater were 4.48 and 4.68
      respectively, and 88% and 91% of rain events were acidic in 2004 and 2005,
      respectively. The contribution of SO4(2-) to Shenzhen rainwater acidity was
      smaller than that in northern cities and NO3- and Cl- played an important part to
      acidification of Shenzhen precipitation. The contribution of Cl- and Na+ to
      rainwater chemical components was higher, indicating the significant marine
      influence on Shenzhen precipitation. The secondary components like SO4(2-), NO3-
      and NH4+ contributed significantly to total ions of rainwater and they accounted
      for more than 40% of total ions in 2004 and 2005, which indicated the severe
      secondary pollution in Shenzhen. There was the obvious difference in origins for
      different rainwater components. Cl-, K+ and Na+ were mainly from marine
      contribution while SO4(2-), NO3-, Ca2+ and Mg2+ were mainly from non-sea salt
      fraction. Formic acid, acetic acid and oxalic acid were most abundant low
      molecular weight organic acids and the sum of their concentrations accounted for
      94% and 99% of total organic acids determined in 2004 and 2005, respectively.

PMID- 18637356
TI  - [Profile variability of soil properties in check dam on the Loess Plateau and its
      functions].
AB  - To understand the profile variability of soil properties of check dam and its
      possibility of engineering control over non-point source pollution, we used
      classical statistics to characterize the profile change of soil properties of a
      5.20 m depth soil profile in the typical check dam on the Loess Plateau. The
      roles of check dam as organic carbon storage and available nutrients storage were
      discussed. The results showed that: 1) The bulk density and sand content of dam
      head were lower than dam-tail, while, soil water content, silt, loam, organic
      carbon, available P, NO3(-) -N and NH4+ -N were higher than dam-tail. The bulk
      density for both dam-head and dam-tail showed weak variability while other
      properties showed moderate variability. All variables followed a normal
      distribution except sand in dam-head and soil moisture in dam-tail. 2) The change
      pattern of soil moisture on the soil profile for both dam-head and dam-tail was
      saw-tooth type. The change trends of soil organic carbon, available P and NH4+ -N
      were comparable to that of soil moisture. 3) The correlations among soil water
      content, organic carbon, bulk density, silt, loam, sand, available P, NO3(-) -N
      and NH4+ -N were significant (p < 0.05) except the relationship between bulk
      density and NO3(-) -N, NH4+ -N and relationship between available P and NH4+ -N
      in dam-tail. The positive or negative correlation of soil properties both in dam
      head and dam-tail were coincident. 4) The check dam can be an important carbon
      storage on the Loess Plateau, and the organic carbon storage in dam-head was
      higher than dam-tail. The storage of organic carbon in 400-520 cm depth was the
      biggest for dam-head, in 0-100 cm depths for dam-tail. 5) The check dam is an
      enrichment sink of available nutrients. The storage of available P, NO3(-) -N and
      NH4+ -N in dam-head were higher than dam-tail, and the range of storage was: NH4+
      -N > available P > NO3(-) -N. The coefficient of enrichment for NH4+ -N and NO3(
      ) -N were 1.132 and 1.956, respectively. 6) As the sink of soil nutrients, check
      dam has an important theoretical value for region carbon balance, ecological
      environment reconstruction and the effective control over non-point source
      pollution.

PMID- 18637357
TI  - [Crust development and subsurface soil properties under dominant shrubs in the
      process of dune restoration, Horqin Sand Land].
AB  - Soil crust is a common and widespread phenomenon in desert areas all over the
      world due to its extraordinary ability to survive desiccation and extreme
      temperatures, high pH and salinity. Despite its unassuming appearance, biological
      soil crusts play a significant role in desert ecosystems, including involvement
      in the process of formation, stability and fertility of soil, preventing soil
      erosion by water or wind, increasing the possibility of vascular plant
      colonization, and being responsible for the stabilization of sand dunes. This
      study taking Horqin Sand Land as research region, by field sampling, crust and
      topsoil (0-2.5 cm and 2.5-5 cm under crust) samples in different dune habitats
      and shrub communities were collected, and their physicochemical properties were
      analyzed, including particle size distribution, bulk density, total nutrients and
      available nutrients, pH, EC and CaCO3 content. The result revealed that Artemisia
      halodendron in semi-mobile dune, Caragana microphylla in semi-fix dune, Artemisia
      frigida in fix dune and Salix microstachya in interdunal lowland were
      respectively developed physical soil crust, algae crust, lichen crust and moss
      crust. Crust thickness, hardness, water content, fine fraction, total and
      available nutrients gradually increased by semi-mobile dune < semi-fix dune < fix
      dune < interdunal lowland in terms of different dune habitats, and by physical
      soil crust < algae crust < lichen crust < moss crust in terms of different crust
      types. There were significant differences among crust types on nutrient content
      and particle size distribution (p < 0.01). Meanwhile, crust enhanced the < 0.05
      mm content and nutrient content of topsoil, following an increasing trend from
      semi-mobile dune to interdunal lowland. As to each crust, the parameters of 0-2.5
      cm subsurface soil layer were higher than that in 2.5-5 cm soil layer. The result
      also showed that the fine fraction and nutrient content of moss crust under Salix
      microstachya in interdunal lowland were higher than others, so did the 0-5 cm
      subsurface soil under it.

PMID- 18637358
TI  - [Characteristics of phosphorous release from soil in periodic alternately
      waterlogged and drained environments at WFZ of the Three Gorges Reservoir].
AB  - The water-fluctuation-zone (WFZ) of reservoir and big river had special
      environmental characteristics that were a joint of aquicolous and terrestrial
      ecological system. According to the WFZ' s alternately waterlogged and drained
      environment, the control experiment for phosphorous release with purple alluvial
      soil of the water-fluctuation-zone (WFZ) at the Three Gorges Reservoir were
      carried out. Research was focused on the characteristics of phosphorous release
      from soil in the WFZ in periodic inundating-draining environment. Results showed
      that the release of T-P increased after each inundating process, from 15.4 mg x
      kg(-1) at first time to 26.5 mg x kg(-1) at third time. The activity of each
      phosphorous fraction at the water-soil interface in alternately inundating
      draining conditions followed the sequence of Ca2-P, Fe-P > Ca8-P, Al-P > O-P >
      Ca10-P. The main impetus of phosphorous release at continuing inundating
      condition was the solubilization of Ca2-P and the transformation of Fe-P at
      alternately oxidizing-deoxidizing conditions; and the main impetus of phosphorous
      release at alternately inundating-draining conditions was the latter. In
      addition, inundation could not make O-P release from the soil, but it activated O
      P which transformed to Fe-P when drained and Fe-P could be released when
      inundated again. The activeness of Ca2-P was highest among all kinds of
      phosphorous, and its concentration is from 14 mg x kg(-1) at beginning of
      inundated process to 5 mg x kg(-1) at end of inundated process. The results
      showed there was an increase of activated O-P after each waterlogged period, and
      a decrease after each drained period.

PMID- 18637359
TI  - [Responses of CO2 fluxes to light intensity and temperature in rice paddy field].
AB  - CO2 fluxes in rice paddy ecosystem in subtropical hilly region were measured
      continuously using eddy covariance technique. The objectives were to investigate
      the responses of CO2 fluxes to light intensity and temperature in the paddy
      ecosystem. Results showed a rectangular hyperbolic light-response function could
      be used to describe the relationship of CO2 flux and photosynthetic photon flux
      density (PPFD). The absolute values of CO2 fluxes increased with the increment of
      PPFD. When PPFD was higher than 1000 micromol/(m2 x s), the maximum was observed.
      CO2 fluxes responded differently to light between early and late rice. Values of
      quantum yield of late rice (0.0465-0.0999 micromol/micromol) were general higher
      than that of early rice (0.0176-0.0541 micromol/micromol). Moreover, the quantum
      yield and the maximum rate of photosynthesis assimilation in the blooming stage
      were higher than that in tillering and ripening stages. In nighttime, respiration
      from soil and plants (ecosystem respiration, Reco) changed exponentially with the
      increase of soil temperature at the depth of 5 cm (T5), 10 cm (T10), and 20 cm
      (T20), respectively. Whereas, T5 was more feasible than others to be considered
      as the temperature parameter for Reco calculation. During early rice growing
      season, Reco was more sensitive to temperature change than that during late rice
      growing season.

PMID- 18637360
TI  - [Modeling the ammonia volatilization from common urea and controlled releasing
      urea fertilizers in paddy soil of Taihui region of China by Jayaweera-Mikkelsen
      model].
AB  - The ammonia volatilization on the Typic Gleyi-stagnic Anthrosol with application
      of common urea and controlled release urea (LP-S100) fertilizers in the rice
      seasons in paddy soil of Taihui region of China was modeled by Jayaweera
      Mikkelsen model. Results showed great difference of ammonia volatilization from
      two type fertilizers was detected with lysimeter experiment in the rice season.
      Nitrogen loss via ammonia volatilization after common urea application with
      conventional ways was 29%-35%, while only 5% of controlled release urea-N was
      volatilized. The Jayaweera-Mikkelsen model was over estimated the total amount of
      ammonia volatilization in the whole season, and great deviation from the measured
      data was obvious for the higher volatilization from common urea fertilizer. The
      estimated data were 2.95-4.19 times of the measures one for common urea
      treatments, while they were 1.19-1.40 times of those measured for LP-S100
      treatments. The order of magnitude quotient was one of the indicators to evaluate
      the model estimation. The value of it was 0.8, which indicated the estimation of
      the model need improvement. Though sensitive analysis for the five parameters in
      the model was tested and amended the parameter of the concentration of NH4+ -N, a
      limited term was inducted in the model operation. The amended model got better
      results as the ratio of estimation to measured data was decreased to 1.12-1.28.
      The alga activity in the paddy field influenced ammonia volatilization and might
      make the failure of the model estimation of the original model.

PMID- 18637361
TI  - [Relationship between surface UV radiation and air pollution in Beijing].
AB  - Based on the data of solar radiation and air pollutants collected in Beijing, the
      relationship between surface ultraviolet (UV) radiation and the content of air
      pollutants were analyzed, using the radiative transfer model TUV4.4 (Tropospheric
      Ultraviolet Visible). The results show that average total ozone content is 329 DU
      and higher in winter and spring, lower in summer and autumn. The inverse
      relationship exists between ground level UV radiation and total ozone content.
      This study also shows that a substantial reduction (up to 50%) in the UV
      radiation on days with high levels of air pollution. Larger fluctuations are
      found in UV radiation in the summer. The effects of clouds and air pollution on
      UV are higher than on total solar radiation, and the reduction in UV is about
      twice as large as the total solar radiation values. Strong reduction in the UV
      radiation reaching the ground is associated with the increase of tropospheric
      ozone and nitrogen oxides in Beijing. The correlation coefficient between ozone
      concentration and decrease in UV radiation is 0.70 in the early afternoon.

PMID- 18637362
TI  - [Comparison analysis of variation characteristics of SO2, NOx, O3 and PM2.5
      between rural and urban areas, Beijing].
AB  - The concentrations of SO2, NOx, O3 and PM2.5 were observed continuously at
      Shangdianzi atmospheric background monitoring station and Baolian urban
      environmental monitoring station from 2006-01-01 to 2006-12-31. The difference of
      seasonal variation and diurnal variation between rural and urban areas was
      analyzed. And the relationship between wind direction and pollutant concentration
      at background station was discussed. The results showed that. 1) The difference
      of NOx and SO2 concentrations between rural and urban was most prominent in
      winter. The concentrations in urban had 4-6 times more than that in rural. The
      variation trends of O3 were similar in urban and rural. PM2.5 was more than 100
      microg/m3 in April and May in rural, which was 2-3 times more than annually
      average. 2) The diurnal variation of NOx and SO2 showed two peaks, one around
      09:00 and the other around 22:00. That showed one peak around 22:00 in rural. The
      rural ozone daily peak was 2 h later than the urban. The diurnal variation of
      PM2.5 was not regular. 3) The pollutant concentrations seemed obviously high when
      southwest wind prevailed and brought the polluted air from urban. Contrarily,
      that was very low when northeast wind prevailed and brought the clean air.

PMID- 18637363
TI  - [Isolation and characterization of a phenanthrene-degrading bacterial strain].
AB  - A bacterial strain that degrades phenanthrene was isolated from activated sludge
      of wastewater treatment plant from a chemical corporation. The strain can utilize
      phenanthrene as sole source of carbon and energy. It was identified as
      Burkholderia sp. according to morphological and 16S rRNA gene sequence analysis.
      Phenanthrene (100 mg x L(-1)) was removed 74.1% within 84 h by this strain. It
      was suggested that the strain possessed the salicylic acid pathway by LC-MS and
      UV methods. And the strain contains an inductive catechol 2,3-dioxygenase (C230).
      The kinetic constants Km and Vmax were 10.93 micromol x L(-1) and 106.38 micromol
      x min(-1), receptively. It indicates that the affinity of the endoenzyme to
      catechol is great and catechol is a better substrate.

PMID- 18637364
TI  - [Preparation and characterization of parathion sensor based on molecularly
      imprinted polymer].
AB  - A novel electrochemical sensor for the detection of parathion based on
      molecularly imprinted polymer of self-assembled o-aminothiophenol onto gold
      electrode was constructed. The polymerization solution was prepared from a 10
      mmol/L parathion, 5 mmol/L tetra-n-butylammonium perchlorate, 30 mmol/L o
      aminothiophenol solution of dichloromethane. Electropolymerization was carried
      out over 30 cycles between -0.3 V and 1.4 V. The template molecules were removed
      from the modified electrode surface by washing with 0.5 mol/L hydrochloric acid.
      Cyclic voltammetry was employed in the process of electrochemical measurements.
      The experimental results show that the optimum acidity of background solution is
      pH 6.8 and the optimum incubation time is 10 min. A highly linear response to
      parathion in the concentration range of 1.0 x 10(-4)--5.0 x 10(-7) mol/L is
      observed, with a detection limit of 2.0 x 10(-7) mol/L estimated at a signal-to
      noise ratio of 3. The sensor has been applied to the analysis of parathion in
      real sample with recovery rates ranging from 98.0% to 104%. Parathion imprinted
      and nonimprinted polymer films were exposed to a series of closely related
      compounds, e.g. methyl-parathion, paraoxon, phoxim, omethoate, nitrobenzene and o
      , m-, p- nitrophenol, and the sensor exhibited good selectivity and sensitivity
      to parathion.

PMID- 18637365
TI  - [Recognition and analysis on primary metabolites of nonylphenol].
AB  - In order to discuss the nonylphenol (NP) biodegradability effect in the
      wastewater treatment process, the primary metabolites and route of NP had been
      analyzed in the molecular level by the interpretation of gas chromatography mass
      spectrometry (GC-MS) and the two experimental methods. A method was that
      activated sludge degraded two types of simulating sewage comparatively. Type-1
      wastewater was made up of water, glucose, peptone and inorganic salts, and type-2
      sewage was mixed up of NP and type-1 as comparison wastewater. The other
      experiment was that dominant bacteria group metabolized the culture medium
      contained NP as only organic carbon source. The results show that the NP primary
      metabolites from the activated sludge experiments are a series of short chain
      alkyl phenols with butyl, amyl or hexyls. There are different methyl branch
      structures correlated with isomerous nonyl of NP in the alkyls. The primary
      metabolites from the dominant bacteria experiment have alkyl phenols and benzene
      acetic. The bio-degradation pathways of NP would be that the long branches in
      nonyl of NP are firstly degraded into short methyl branches, which come into
      being a series of short chain alkyl phenols with different branch structures. The
      middle products should be further metabolized into simpler compounds, such as
      benzene acetic. Based on the endocrine disrupter characteristic of alkyl phenol
      compounds, the short chain alkyl phenol compounds still have estrogen hormone
      effect, and their environmental effect must be pay attention in the pollutant
      control of NP.

PMID- 18637366
TI  - [Bacterial community composition of the Yellow Sea Cold Water Mass studied by PCR
      denaturing gradient gel electrophoresis].
AB  - Bacterial community composition and predominant bacteria were analyzed by PCR
      denaturing gradient gel electrophoresis (DGGE) in the Yellow Sea Cold Water Mass
      (YSCWM). The results analysed by Glyko Bandscan software showed that samples from
      all stations in April and stations in the YSCWM area in October had almost the
      same number of different DNA bands (17 and 16 respectively ) with high diversity.
      However, samples from the stations out of YSCWM area had fewer DNA bands (about
      12) with lower diversity. 24 DGGE bands reflecting varying phylotypes were
      excised, cloned and sequenced. Phylogenetic analysis of 24 cloned bands showed
      that bacterial phylotypes were made up of two phyla bacteria, Proteobacteria and
      Bacteroides. Among these sequences, 16 were related to gamma-Proteobacteria and
      delta-Proteobacteria and 5 were related to Bacteroides. It indicated that
      bacterial community composition, as well as the predominant bacterial groups,
      from all sampling stations in April (the temperature of seawater was around 7-12
      degrees C) and the inter of YSCWM in October (< or = 10 degrees C) was the same,
      different from the exterior of YSCWM (> or = 19 degrees C). By comparing, from
      samples of exterior of YSCWM, the predominant bacteria groups were different with
      the different sampling stations. So it suggested that bacterial community
      composition and the characteristic of predominant bacteria of the YSCWM may have
      something to do with the development of the YSCWM.

PMID- 18637367
TI  - [Microbial diversity analysis in rotating drum biofilter for nitric oxide
      denitrifying removal].
AB  - PCR-DGGE was applied to analyze the microbial communities in rotating drum
      biofilter (RDB) for nitric oxide denitrifying removal under anaerobic conditions.
      The 16S rRNA genes (V3 region) were amplified with two universal primers (338F-GC
      and 518R). These amplified DNA fragments were separated by parallel DGGE. The
      DGGE profiles of biofilm samples from different sections of RDB are similar and
      about sixteen types of microorganisms are identified in the biofilm samples.
      These results show that microbial diversity of RDB firstly increases but then
      decreases with the addition of Cu II (EDTA) and the increase of NO removal
      efficiency. However, the change of microbial community is not significant during
      the process. Eight major bands of 16S rRNA genes fragments from DGGE profiles of
      biofilm samples were further eluted from gel, re-amplified, cloned and sequenced.
      The sequences of these fragments were compared with the database in GeneBank
      (NCBI). The gene analysis of 16S rRNA showed that the major populations are
      Cytopahga-Flexibacteria-Bacteroides (CFB) group Bacteroides, beta 
      Proteobacterium, gamma-Proteobacterium and Clostridium sp.. In addition,
      denitrification is related with band G-5, G-6 and G-8. G-5 is affiliated with
      gamma-Proteobacterium. Both G-6 and G-8 are affiliated with beta-Proteobacterium.

PMID- 18637368
TI  - [Cultivation and isolation of bacteria coupling nitrogen removal from wastewater
      and hydrogen sulfide removal from biogas].
AB  - It was studied that during the startup of reactors the crucial bacteria coupling
      nitrogen removal from swine wastewater and hydrogen sulfide removal from biogas
      using bubbling absorption reactors without seeding sludge, with seeding anaerobic
      sludge and aerobic sludge, respectively. During the prophase of the experiment
      (before the 26th d), the removal rate of nitrogen and hydrogen sulfide were from
      50% to 64% in reactors with seeding sludge, that in the reactor without seeding
      sludge was only 11%-14%. At the end of experiment (the 56th d after startup), the
      removal rates of nitrogen for three reactors were about 90%. The removal rates of
      hydrogen sulfide were more than 70%. The result showed that though the finishing
      time for startup of the reactor without seeding sludge was longer than that with
      seeding sludge, it could be obtained the same effect of removal of nitrogen and
      hydrogen sulfide as the latter after two months cultivation. In the different
      period of startup of the reactors, the variation of the population of bacteria
      was studied, which had the same trend as the removal effect of nitrogen and
      hydrogen sulfide. Two strains which could remove the nitrogen and hydrogen
      sulfide more than 60% simultaneously were isolated from the three reactors, and
      primarily identified as Thiobacillus denitrificans and Pseudomonas respectively,
      based on their morphology and physiological characters.

PMID- 18637369
TI  - [Research on single phase high solid anaerobic digestion of organic fraction of
      municipal solid wastes].
AB  - Under mesophilic condition (35 degrees C), a bench-scale experiment based on high
      solid anaerobic digestion process was conducted in a fed-batch single phase
      reactor to treat the OFMSW. The experiment has lasted for more than half a year
      and significant results were obtained. At the start-up stage, acidification
      occurred and showed large inhibition to gas production and the gas production
      rate once dropped to 0. After pH conditioning, the system has recovered and began
      to stably running. In this period, gas production rate reached 746.33 L/kg
      volatile solids (VS) [3.69 L/(L x d)] when the total solids (TS) content of the
      feeding waste was 24.79% and the VS content was 23.06%. The organic loading rate
      and hydraulic retention time(HRT) was 4.94 kg/(m3 x d) and 47 d respectively.
      However, with time went by, accumulated ammonia exceeded its limited value, which
      is deduced as 2000 mg/L, and the gas production rate dropped below half of the
      maximum value. By adding chemicals to diminish the amount of ammonia and
      adjusting the C/N of the feeding, inhibition was relaxed and gas production rate
      increased gradually.

PMID- 18637370
TI  - [Characteristics of municipal sludge and vacuum filtration thickening process].
AB  - It was found that sludge total solid (TS) concentration was equal to chemical
      oxygen demand (COD), while volatile solid (VS) was 1.5 times of COD
      concentration. R2 of linear regression of TS and VS with COD was 0.9314 and
      0.9228 respectively. Total COD in sludge was approximately 60% of that removed in
      water treatment process. Sludge contained high level protein and low fat. The TS
      of present gravity thickening sludge was universally lower than 3.3%. Efficiency
      of vacuum filtration process was determined by sludge type, sludge solid
      concentration, PAM molecular weight and PAM addition dose. Under - 34.7 kPa
      pressure, sludge dry solid filtration thickening rate of primary sludge was up to
      31 kg/(m2 x h). While, for wasted actived sludge the rate was lower than 15
      kg/(m2 x h). Rate of gravity thickening sludge was up to 43 kg/(m2 x h). TS of
      vacuum filtrate were lower than 1.5 g/L.

PMID- 18637371
TI  - [Study on vitrification of fly ashes from municipal wastes incinerator with a
      plasma torch].
AB  - TCLP analysis (USEPA method 1311) was employed on fly ash in order to analyze the
      metals leachability and the concentration of cadmium was 0.3225 mg/L which
      exceeded state TCLP standard(0.3 mg/L). According to USEPA method 1613, I-TEQ of
      PCDD/Fs in fly ash was 0.45 ng/g. Then a double arcs DC plasma torch was
      developed to vitrified fly ash. And the results showed that heavy metals were
      mostly immobilized in the vitrified slag and also I-TEQ of PCDD/Fs in fly ash was
      destroyed near 91.6%. The morphology of vitrified slag was amorphous state which
      showed the glassy slag of SiO2 and the microstructure of slag was very compact.

PMID- 18637372
TI  - [Chelating stabilization of heavy metals in fly ash from municipal solid waste
      incinerators for co-disposal in sanitary landfill].
AB  - The characteristics and leaching behavior of heavy metals in fly ash, sampled
      from 4 MSWI plants, were investigated in this study. The results indicated that
      the main elements of fly ash were Si, Ca, Al, Cl, and heavy metals such as lead,
      zinc, copper, chromium and cadmium were enriched in fly ash which had great
      environmental risk. However, co-disposal of fly ash in sanitary landfill was an
      available and practical resolvent. For disposal security, the leaching procedure
      of toxicity basing on co-disposal scenario, which had been implemented from 1st
      May 2007, had increased the acidity of leachant to 0.3 mol x L(-1). The
      experiments of chelating stabilization technology using dithiocarbamate were
      carried out for MSWI fly ash treatment. The results indicated that heavy metals
      in fly ash were fixed by DTC in manner of chelating reaction. With the amount of
      additive reaching 3% (mass fraction), the concentrations of heavy metals in
      leachate of these fly ash samples could meet the demand of co-disposal in
      sanitary landfill.

PMID- 18637373
TI  - [Leaching and stabilization of heavy metal in the fly ash of medical wastes].
AB  - Through the experiments of leaching and melting on the fly ash of medical wastes,
      the influence of leaching time, L/S, pH and grain size on the leaching
      characteristics of heavy metal and the effect of melting on the stabilization of
      fly ash are studied. Results show that, following the leaching time extending,
      the leaching concentrations of heavy metals and lixiviate toxicity of heavy
      metals increase in the fly ash. When the ratio of liquid and solid add, the
      leaching concentrations of heavy metals obviously become big, and the Cd's
      leaching concentration is the biggest, when the ratio of liquid and solid is 90,
      the Cd' s leaching ratio exceed the percent of 70. At the time pH is about 7, the
      leaching concentrations of heavy metals are the lowest. When the grain size is
      the bigger or little, the leaching concentrations of heavy metals are lower,
      however when the grain size is 250-900 microm, the concentrations are higher.
      After fly ash melt in the high temperature, the lixiviate toxicity of heavy
      metals greatly reduce, which explains that the effect of melting on heavy metals'
      stabilization is very good.

PMID- 18637374
TI  - [PCDD/F formation and its mass balance in a MSW incineration system].
AB  - PCDD/F distributions in a two-stage reciprocating grate municipal solid waste
      (MSW) incinerator under two kinds of operating conditions were investigated by
      sampling the ashes, flue gases and bottom ashes at different positions, and the
      mass balance was calculated. At the boiler outlet, the concentration of PCDD/F in
      the flue gas is 2.602 ng x m(-3) and 1.236 ng x m(-3) under operating condition 1
      (RUNI) and operating condition 2 (RUN2), respectively. A significant formation of
      PCDD/F was found in the sections of semi-dry scrubber (SDS) and cyclone
      precipitator (CP), in which the temperature of flue gas was in the range of 260
      180 degrees C. Compared with PCDD/F level measured at the boiler outlet, the
      total concentration of tetra-to octa-CDD/F measured at the CP outlet increased
      82.2% and 17.6% under RUN1 and RUN2, respectively. At the bag filter (BF)
      section, about 90% of PCDD/F was removed from the flue gas by the precipitation
      of fly ash. The PCDD/F homologue patterns were almost similar for the boiler ash,
      CP ash, BF ash and the flue gases. The higher O2 content in flue gas led to a
      larger PCDD/F yield, but the variation of O2 level did not give rise to a
      systematical change of PCDD/F homologue pattern. Under RUN1, 10.4%, 3.2%, 9.3%,
      64.1% and 13.0% of formed tetra-to octa-CDD/F were distributed into bottom ash,
      boiler ash, CP ash, BF ash and emission gas, respectively. The corresponding
      values were 8.6%, 8.0%, 9.4%, 66.7% and 7.3% for RUN2, respectively.

PMID- 18637375
TI  - [Comparison of fixation effects of heavy metals between cement rotary kiln co
      processing and cement solidification/stabilization].
AB  - Both cement rotary kiln co-processing hazardous wastes and cement
      solidification/stabilization could dispose heavy metals by fixation. Different
      fixation mechanisms lead to different fixation effects. The same amount of heavy
      metal compounds containing As, Cd, Cr, Cu, Pb, Zn were treated by the two kinds
      of fixation technologies. GB leaching test, TCLP tests and sequential extraction
      procedures were employed to compare the fixation effects of two fixation
      technologies. The leached concentration and chemical species distribution of
      heavy metals in two grounded mortar samples were analyzed and the fixation
      effects of two kinds of technologies to different heavy metals were compared. The
      results show the fixation effect of cement rotary kiln co-processing technology
      is better than cement solidification/stabilization technology to As, Pb, Zn.
      Calcinations in cement rotary kiln and then hydration help As, Pb, Zn contained
      in hazardous wastes transform to more steady chemical species and effectively
      dispose these heavy metals compounds. Cr3+ is liable to be converted to much more
      toxic and more mobile Cr6+ state in cement rotary kiln. And so Cr wastes are more
      fit for treatment by cement solidification/stabilization technology. The work
      could provide a basis when choosing disposal technologies for different heavy
      metals and be helpful to improve the application and development of cement rotary
      kiln co-processing hazardous wastes.

PMID- 18637376
TI  - [Impact of low-frequencies noise on the ability of thinking and judgment].
AB  - Three typical low frequency noise samples which were collected from some
      associated facilities in urban residential areas and white noise which was
      produced by acoustic apparatus were selected to compare the competence of
      brainwork index (AYP) and error rate in noisy environment with those in quiet
      environment, using dosage exercise method. The result indicates that AYP is lower
      in noisy environment and the error rate is higher than that in quiet environment,
      and there are significant differences between them. The changes of most testees
      in groups that use three different low frequency noise samples respectively are
      more obvious than the group that uses white noise, and the AYP difference attains
      significant level. It indicates that low frequency components are the main
      frequency elements to affect the ability of thinking and judgment. By paired
      samples t-test and frequency spectrums analysis, the results show that the impact
      degree of air condition outdoor unit noise is highest, and noise samples which
      have a peak frequency between 50-300 Hz have a more negative impact on the
      ability of thinking and judgment than other environmental noise.

PMID- 18637377
TI  - [Ecological security evaluation of Heilongjiang Province with pressure-state
      response model].
AB  - The ecological security index (ESI) system including 27 indices for Heilongjiang
      Province was built up with the pressure-state-response (P-S-R) model. The weights
      of the indices were determined by analytical hierarchy process (AHP) and the
      ecological security status classification was evaluated by the ESI model for the
      years of 2000-2005. Then the development trend of ecological security from 2006
      to 2010 was forecasted with the grey dynamic model. The results showed that the
      ecological security ranked the V grade in 2000 and the III grade in 2005,
      indicating the increase of ecological security. The forecasting results show that
      the ecological security will be the III grade for 2006, the II grade for 2007
      2009, and the I grade for 2010 (ideal security). Thus it can be seen that the
      ecological security is ascending year by year, and the ecological environment
      quality is obviously improved with the implementation of eco-province
      construction since 2000. Through the effective facilitation of eco-province
      construction etc., the sustainable and healthy development of ecological security
      will be finally realized in Heilongjiang Province.

PMID- 18637378
TI  - Colonization and deterioration of soft denture lining materials in vivo.
AB  - Colonization of denture lining materials by microorganisms including Candida
      albicans can result in deterioration of the material, as observed by a previous
      in vitro study by the authors. The current in vivo study monitored the microbial
      colonisation and penetration of five types of denture liners and their topography
      over six months. There was no significant difference in the microbial
      colonisation on the denture liners and no penetration observed, indicating a
      slower rate of deterioration of materials in vivo. However the surface roughness
      of all materials increased during use, which might alter susceptibility to
      subsequent microbial colonisation.

PMID- 18637379
TI  - A survey on orthodontic-restorative dental services in a NHS hospital.
AB  - The provision of a joint orthodontic-restorative hospital service is important in
      providing a quality service for some dental malocclusions. A prospective survey
      was carried out of the joint orthodontic-restorative clinic at Mayday University
      Hospital, during the months of January to August 2005. Data was collected using a
      data collection form. In total 61 patient's attended 4 joint clinics. Fifty per
      cent of referrals were by general dental practitioners. The commonest referral
      reasons were spacing and dental trauma. Over one third of patients were seen
      within 12 weeks of their referral, whilst two thirds start their treatment within
      12 weeks of consultation. The commonest restorative treatment was periodontal
      therapy, crown and bridgework. Over one third of patients required joint
      orthodontic and restorative treatment. More than 12% of patients require oral
      surgery in the form of removal of impacted teeth, exposure of unerupted teeth,
      placement of bone anchors or orthognathic surgery. Consultation and treatment
      waiting times could be reduced by the introduction of more clinics and employment
      of more staff A representative in oral surgery maybe useful with the increase use
      of bone anchors and mini implants to aid joint orthodontic-restorative treatment.
      Access to an orthodontic and restorative consultant clinic is useful in providing
      patients with a high quality of multidisciplinary treatment planning in an
      efficient manner.

PMID- 18637380
TI  - Retentive characteristics of Ankylos SynCone conical crown system over long-term
      use in vitro.
AB  - 18 Ankylos SynCone conical crowns with 4-degree angle and 18 SynCone conical
      crowns with 6-degree angle were tested in vitro for a total of 5,000 insertion
      separation cycles to investigate their retentive characteristics. Under 20 N
      insertion force, the retentive force of Ankylos SynCone conical crown system was
      between 5 and 10 N. The rententive force kept almost constant during the entire
      testing cycles. It was thus shown that the SynCone conical crown system could
      potentially provide adequate and constant retentive force to retain implant
      supported overdentures. It may be considered to retain implant-supported
      mandibular overdentures as an alternative to bar attachments.

PMID- 18637381
TI  - The use of implants at an increased vertical dimension of occlusion to correct a
      scissor bite: a case report.
AB  - Traditional methods of achieving anchorage for orthodontic treatment are
      dependant on the presence of a sufficient number of teeth with adequate root
      support. With the success and predictability of osseo-integration, dental
      implants are being used frequently to obtain absolute anchorage. This case report
      illustrates the successful use of implants with a combined orthodontic
      restorative approach to obtain anchorage in a partially dentate patient to
      correct a transverse cross-bite (scissor bite) relationship. The implants were
      subsequently restored to replace missing posterior teeth. The importance of a
      multi-disciplinary approach to planning and close liaison between the
      orthodontist, surgeon and restorative dentist during the treatment phase are
      discussed.

PMID- 18637382
TI  - Effect of a laboratory surfactant on compatibility of type IV dental stones with
      addition-cured silicone impression materials.
AB  - This study compared the effect of a surfactant on surface detail reproduction
      between combinations of addition-cured silicone impression materials and type IV
      stones. Six hundred impressions were made of a ruled test block using; Examix
      NDS, Doric-Es Flo-Light, Panasil Contact Plus, Extrude Wash and President Plus
      Jet. Half of the impressions were treated with a surfactant (Aurofilm).
      Impressions were poured with type IV dental stones; Silky Rock, Fuji Rock,
      Suprastone and Vel-Mix and the 20 mu line was scored. A laboratory surfactant
      (Aurofilm) significantly reduced (P<0.01) compatibility with; (i) Examix-NDS and
      Suprastone, (ii) Examix-NDS and Velmix, (iii) Extrude Wash and Fuji Rock.

PMID- 18637383
TI  - Effect of surfactant on surface hardness of dental stone and investment casts
      produced from polyvinyl siloxane duplicating materials.
AB  - Polyvinylsiloxane duplicating materials are typically treated with a topical
      surfactant before pouring dental models, but the use of topical surfactants in
      the dental laboratory may affect the surface hardness of the resultant models.
      The effect of two different topical surfactants on surface hardness of two dental
      stones (FujiRock and Dentstone) and one phosphate bonded investment material
      (Croform WB) produced from polyvinyl siloxane (PVS) dental laboratory duplicating
      moulds was investigated. Topical surfactants affected the surface hardness of
      FujiRock, Dentstone and Croform WB investment material. Surface hardness of
      FujiRock increased with Wax-Mate surfactant. However, surface hardness of Croform
      WB investment material decreased with both topical surfactants.

PMID- 18637384
TI  - A long term study on residual monomer release from denture materials.
AB  - The aim of this long term study was to investigate the release of residual
      monomer from different denture materials, throughout a 38 months time period
      after curing and storage in water Specimens made of four denture base resins
      (three heat polymerizing, one auto polymerizing) and one hard liner were
      subjected to residual monomer determination using gas liquid chromatography. The
      residual monomer estimation carried out on three occasions: one week, 12 months
      and 38 months after curing. The data obtained were analyzed using two-way Anova
      followed by Scheffe's test for post hoc multiple comparisons at alpha=0.05. Heat
      polymerized denture base acrylic resins showed less residual monomer than auto
      polymerized ones (p<0.001) and released no statistically significant amounts of
      monomer (p>0.05), during the 38 months storage time period. Auto polymerized
      denture materials, which had higher residual monomer content, released
      statistically significant amounts of monomer (p<0.001) during the first twelve
      months storage, but not during the last twenty six months period (p>0.05). Heat
      polymerized denture base acrylic resins released insignificant amounts of
      residual monomer during the storage period, whereas both the auto polymerized
      denture base resin and the hard liner released significant amounts of residual
      monomer during the initial storage time period but insignificant ones during the
      remainder of the storage period.

PMID- 18637385
TI  - Shear bond strength between nickel-chromium and human dentine using a dual-cure,
      self-adhesive universal resin luting agent.
AB  - The adhesive property of a dual-cure, self-adhesive universal resin luting agent
      (Rely X Unicem, 3M ESPE) between nickel-chromium (Ni-Cr) and human dentine was
      compared with three conventional resin luting agents (Calibra, Dentsply; Panavia
      F, Kuraray; All-bond 2 C & B cement, Bisco). Ten Ni-Cr rods were bonded to human
      dentine with each of the four luting agents, and were subjected to shear bond
      test. Results showed that there was no significant difference in shear bond
      strengths among the luting agents. A dual-cure, self-adhesive universal resin
      luting agent was shown to have comparable adhesive property between Ni-Cr and
      human dentine as three other conventional resin luting agents. Given the
      simplicity of use of the dual-cure, self-adhesive universal resin luting agent,
      it appears to be promising in clinical applications.

PMID- 18637386
TI  - Influence of betel nut chewing, dental care habits and attitudes on perceived
      oral health among adult Pakistanis.
AB  - PURPOSE: To survey an adult population in a deprived district of Karachi, with
      reference to factors influencing perceived oral health. MATERIALS AND METHODS: Of
      1000 questionnaires distributed to households, 994 were returned. The respondents
      were aged between 30 and 50 years old. Women comprised 49% of the sample.
      RESULTS: Pan and betel nut chewing had a strong influence on the perceived oral
      health of the respondents. Pan chewers, 32% of the respondents, had a greater
      risk of oral problems, odds ratio 3.63. In contrast to other oral problems,
      dental caries was significantly less frequent among pan chewers (odds ratio
      0.63). Betel nut chewing (28%) was less deleterious to oral health: the only
      significant effects were a higher risk for dental caries, odds ratio 4.51, and
      more gingival bleeding. While most of the respondents used a toothbrush for oral
      hygiene, a substantial proportion (27%) used their fingers. The oral hygiene
      method had no influence on the perceived oral health, nor did consumption of
      sweets and tea with sugar. Over 80% of the participants seldom or never visited a
      dentist. Cleaning frequency was significantly associated with oral health: those
      who cleaned their teeth at least daily had fewer oral problems. Almost all
      participants considered that eating sweets, smoking, and chewing pan and betel
      nuts endangered oral health. CONCLUSIONS: In this population, typical of deprived
      urban areas of Pakistan, betel nut habits and frequency of oral hygiene have a
      strong influence on perceived oral health, while cleaning method and sugar intake
      do not.

PMID- 18637387
TI  - Investigating the relationship between self-reported oral health status, oral
      health-related behaviours and self-consciousness in Romania.
AB  - PURPOSE: The aim of the present study was to investigate whether self
      consciousness, self-reported oral health status and oral-health-related
      behaviours were associated. MATERIAL AND METHODS: The present study sample
      consisted of 253 first year medical students in Romania. The questionnaire
      included information about socio-demographic factors, behavioural variables, self
      reported oral health status and three self-consciousness subscales (Private Self
      Consciousness, Public Self-Consciousness, and Social Anxiety). RESULTS:
      Significant differences were found in Public Self-Consciousness and Social
      Anxiety according to several variables: anxiety, stress, depression and current
      non-treated caries. There were significant differences in Social Anxiety for the
      variables of gender, smoking, perceived dental health, self-reported gum bleeding
      and reason for dental visit (p < 0.05). A significant difference was found in
      Public Self-Consciousness for the reason for dental visits (p < 0.05). Total Self
      Consciousness is correlated with anxiety, stress, depression, current non-treated
      caries, gingival bleeding and reason for dental visit. Oral health behaviours
      such as tooth brushing, flossing, mouth washing and last dental visit were not
      influenced by each of the self-consciousness subscales. CONCLUSIONS: The results
      suggest that self-consciousness might be a psychosocial risk marker that
      influences self-reported oral health status.

PMID- 18637389
TI  - The prevalence of malocclusal traits and their correlations in mixed dentition
      children: results from the Italian OHSAR Survey.
AB  - PURPOSE: To know the prevalence of malocclusal traits and their correlation in
      Italian mixed dentition children. MATERIALS AND METHODS: A sample of 1,198
      children 7 to 11 years old, who had never undergone orthodontic treatment, were
      included in the Italian Oral Health of Schoolchildren of the Abruzzo Region
      (OHSAR) Survey. Canine and molar classes, overbite, overjet, dental crowding,
      maxillary midline diastema, crossbite and scissorbite were recorded. The canine
      and molar classes were considered as dependent variables, and their separate
      correlations with all of the other occlusal traits were analysed by multivariate
      methods. RESULTS: Over 90% of the children showed at least one malocclusal trait;
      the mean +/- SD of malocclusal traits was 3.5 +/- 1.8. Gender did not affect the
      prevalence of any malocclusal traits. Dental class II was correlated with
      increased overbite and overjet, and negatively correlated with the maxillary
      midline diastema; dental class III was correlated with decreased overbite and
      overjet, and crossbite. Asymmetrical dental class was correlated with increased
      overjet and crossbite. Dental crowding showed very little correlation.
      CONCLUSIONS: The prevalence of malocclusal traits in Italian children is very
      high, and more effort is needed to implement early interventions, including close
      monitoring and modifications of lifestyle.

PMID- 18637388
TI  - Oral health status of low-income, middle-aged to elderly Hong Kong Chinese with
      type 2 diabetes mellitus.
AB  - PURPOSE: To study oral health conditions, diabetic medical complications and
      their association in type 2 diabetes mellitus (DM). MATERIALS AND METHODS: Cross
      sectional survey of 364 type 2 DM patients (63.6 +/- 10.1 years, 54% female) and
      161 controls (64.1 +/- 10.6 years, 53% female) with or without essential
      hypertension, predominantly low-income, attending a hospital were recruited.
      Periodontal disease (Community Periodontal Index [CPI]) and dental status
      (decayed, missing and filled teeth [DMFT]) were recorded. Fasting plasma glucose
      and, for DM patients, HbA1C and DM complications were recorded on enrolment and
      follow up, respectively. RESULTS: Many DM subjects had fair diabetic control.
      Both groups (control/DM) had poor oral health: DMFT = 14.5/16.8, CPI 4 = 36%/50%,
      (P < 0.02) while DM subjects had less DT(adjusted) = 2.1/1.4 (P < 0.01). Of the
      follow-up DM individuals, 294 (81%) had medical complication(s). Regression
      analyses showed association between advanced periodontal attachment loss (ALoss)
      and age, male gender, smoking and DM; MT and DMFT were associated with age,
      female gender, smoking, DM and hypertension. ALoss and DMFT were not associated
      with DM complications. CONCLUSIONS: The oral health of the surveyed Chinese
      subjects was poor. Type 2 DM subjects were affected more by ALoss and MT but less
      DT. Subjects with hypertension had higher odds for MT.

PMID- 18637390
TI  - Risk indicators of gingivitis in 5-year-old Brazilian children.
AB  - PURPOSE: To identify the risk indicators of gingivitis among socioeconomic,
      clinical and gender variables in 5-year-old children attending preschools in
      Piracicaba, Brazil, in 2005. MATERIALS AND METHODS: The sample consisted of 728
      subjects attending 22 public (n = 428) and 18 private (n = 300) preschools. A
      previously calibrated examiner performed the clinical examination in an outdoor
      setting, under natural light, using a dental mirror, Community Periodontal Index
      probe and air-drying. Gingival status was measured using the gingival alteration
      index for 5-year-olds according to the national survey carried out in 2002 in
      Brazil (Health Ministry of Brazil, 2004). Socioeconomic variables (monthly family
      income, number of people living in the household, parents' educational level,
      home ownership and car ownership) were collected by means of a parental semi
      structured questionnaire. RESULTS: The prevalence of gingivitis was 16.6%.
      Monthly family income (p < 0.0001), father's education (p < 0.0007), mother's
      education (p = 0.0004), type of school (p < 0.0001), car ownership (p = 0.0854),
      gender (p = 0.0087), initial lesion (p < 0.0001), dental caries (p = 0.0008),
      crowding (p = 0.0054) and spacing (p = 0.0019) were associated with gingival
      bleeding at p < 0.15 and were selected for the regression analysis. By means of
      multiple logistic regression analyses, monthly family income of up to 4 Brazilian
      minimum wages, presence of initial lesion, presence of crowding and male gender
      were found to be risk indicators of gingivitis. CONCLUSION: The prevalence of
      gingivitis in 5-year-old preschool children in Piracicaba was 16.6%. Also, family
      income of up to 4 minimum wages, male gender, the presence of initial caries
      lesion and crowding were risk indicators of gingivitis.

PMID- 18637391
TI  - Profile of periodontal conditions in a Brazilian adult population.
AB  - PURPOSE: To evaluate the periodontal condition of adult patients attending public
      health centres in the city of Recife, Brazil, and to investigate whether
      periodontal conditions are associated with socioeconomic and demographic
      variables. MATERIALS AND METHODS: This cross-sectional study included 13 randomly
      selected public health centres. Sample size was calculated using 5.0% standard
      error and a confidence interval of 95%. The minimum sample size was 461 subjects,
      and a total of 505 subjects participated in this study. Each participant
      completed a questionnaire and underwent periodontal examination. Periodontal
      conditions were based on the Community Periodontal Index (CPI). Bivariate
      analysis of frequencies and means was performed with SPSS, version 11.0. The chi
      square and likelihood ratio statistical tests were used to calculate the level of
      statistical significance of the associations tested. The level of statistical
      significance was set at P < 0.05. RESULTS: Calculus was the highest CPI score in
      61.8% of the subjects, and shallow pockets (4-5 mm) were the highest score in
      15.2% of them. A healthy periodontium was observed in 10.7%, while gingival
      bleeding and deep pockets (> or = 6 mm) were found as the highest CPI score in
      10.3% and 2.0% of the sample, respectively. Periodontal conditions showed
      significant association with the socioeconomic and demographic variables analysed
      (P < 0.05). CONCLUSIONS: Findings indicate a high prevalence of periodontal
      alterations in the sample. Periodontal conditions were worse in men, married
      individuals, older subjects and individuals with low socioeconomic class and poor
      education.

PMID- 18637392
TI  - Periodontal health and its relationship with salivary factors among different age
      groups in a Saudi population.
AB  - PURPOSE: This study aimed to describe the periodontal condition of children,
      adolescents and young Saudi adults and to investigate its relationship with
      salivary variables and oral hygiene status. MATERIALS AND METHODS: A sample of
      114 children, 99 adolescents and 99 young adults were randomly selected from
      patients attending dental clinics at the school of dentistry. Clinical
      examination of oral health status included using WHO Community Periodontal Index
      and Green and Vermillion oral hygiene index. In addition, salivary flow rate, pH,
      buffering capacity and microbial flora were measured. RESULTS: A healthy
      periodontal condition was found in 6.7% of the sample. Calculus was the most
      frequently encountered periodontal disease. Children had better periodontal
      condition than adolescents and adults. Males had higher plaque and gingival
      scores than females. The salivary flow rate and pH were significantly higher in
      individuals with good periodontal condition. The salivary level of fluoride and
      buffering capacity was not related to the periodontal condition. Yeast was the
      only microorganism related to periodontal condition. The relationship between
      poor periodontal condition and high plaque score was highly significant.
      CONCLUSIONS: Periodontal disease increased with age and was strongly related to
      salivary flow rate, pH value and yeast level, as well as plaque accumulation.
      Preventive efforts must be increased in order to achieve the WHO goal for the
      year 2010 of no more than one sextant showing bleeding or calculus at the age of
      15.

PMID- 18637393
TI  - Feasibility of using sodium bicarbonate solution as a damage-limiting strategy
      for erosion lesions.
AB  - PURPOSE: One of the recommended measures to prevent and control dental erosion is
      the oral rinse with sodium bicarbonate solution, which would neutralise the
      dietary acids. However, the prescription of this aqueous suspension has been made
      on an empirical basis. The aim of this in vitro study was to evaluate whether the
      demineralisation caused by erosive episodes could be controlled by the potential
      neutralising effect exerted by a sodium bicarbonate solution. MATERIALS AND
      METHODS: Bovine enamel slabs were embedded in epoxy resin, ground/polished and
      tested for initial surface microhardness. Twice daily for 2 days, specimens were
      subjected to an erosive challenge with orange juice in an orbital shaker.
      Following each erosive episode, specimens (n = 15) were immersed for either 30 or
      60 seconds in a sodium bicarbonate solution or deionised water. The negative
      control group was left untreated. For the remaining daily time, specimens were
      kept in artificial saliva. New microhardness indentations were then made as
      described for the initial measurements. RESULTS: ANOVA applied to the percentage
      of surface microhardness change (%deltaSMH) showed no statistically significant
      difference among treatments (P = 0.5810). CONCLUSION: The use of sodium
      bicarbonate solution, at least under in vitro conditions, may not be a feasible
      strategy for managing enamel erosion.

PMID- 18637394
TI  - Course of changes in salivary pH-values after intake of different beverages in
      young children.
AB  - PURPOSE: The aim of the study was to determine possible differences in decrease
      of pH-values of whole saliva, following the intake of different beverages.
      MATERIALS AND METHODS: Twelve boys and 13 girls (4.9 +/- 0.9 years old)
      participated in this study. A dental examination was performed (dmft). Orange
      juice (pH = 3.67), instant fennel tea (pH = 7.38), whole milk (pH = 6.84) and
      mineral water (pH = 5.88) were tested. All beverages were given at the same time
      of day. Salivary pH and buffering capacities of the beverages were determined
      with a portable pH-meter. Immediately after intake of a beverage, and 5, 10, 15
      and 25 minutes later, whole saliva was collected, and the pH-value was measured
      again. The statistical evaluation was performed using the Wilcoxon test for
      paired samples. RESULTS: Fifteen children had healthy dentitions. Ten subjects
      had a mean dmft of 1.1 +/- 2.3. The mean base salivary pH was 7.09 +/- 0.07,
      without differences between the children with and without dental decay. Mineral
      water led over the whole period of measurements to a significant rise in salivary
      pH (P < 0.05). Orange juice caused a significant reduction in the salivary pH
      during the first 10 minutes. After intake of instant tea or milk, significant
      reductions were found in the period of 5 to 10 minutes. After the intake of
      instant tea, the reduction was still significant after 15 minutes. During the
      period of 5 to 10 minutes, the change in pH (deltapH) in whole saliva differed
      significantly only between consumption of mineral water and other beverages (P <
      0.01). CONCLUSION: With regard to dental health, a regular consumption of orange
      juice or sweetened instant teas should be discouraged.

PMID- 18637395
TI  - Laser fluorescence device does not perform well in detection of early caries
      lesions in primary teeth: an in vitro study.
AB  - PURPOSE: To evaluate if using the laser fluorescence (LF) device improves the
      detection of early or more advanced occlusal caries lesions in primary teeth.
      MATERIALS AND METHODS: A total of 181 occlusal sites in primary teeth were
      assessed by one examiner using DIAGNOdent. The same examiner and a second
      examiner evaluated 72 of the sites again to assess intra- and inter-examiner
      reproducibility. After histological validation, lesions were divided at three
      thresholds according to the lesion depth: outer half of the enamel (D1), inner
      half of the enamel (D2) and dentine (D3). The sensitivity, specificity, accuracy
      and area under ROC curve were calculated for cut-off points for the sample
      considering the aforementioned thresholds. The parameters were compared using chi
      square test and by comparison between unpaired ROC curves. RESULTS: The overall
      LF performance was better at dentine threshold than at enamel threshold. The
      higher specificity was found at D3 and D2, and higher accuracy at D3 (P < 0.001).
      The intra- and inter-examiner agreements were classified as good or excellent for
      all thresholds. CONCLUSIONS: The LF device performs better at the dentine
      threshold than at the enamel threshold. This method does not perform well in
      detecting initial enamel caries lesions.

PMID- 18637396
TI  - [Psychologists and openness concerning the diagnosis of dementia to the patient:
      exploratory research].
AB  - AIM: To explore the openness about the diagnosis dementia amongst psychologists
      the following questions were asked. What is their opinion about openness
      concerning the diagnosis of dementia? What do they actually tell their patients?
      Why do or don't they mention dementia? METHOD: A semistructured questionnaire was
      given to 17 psychologists working in the North of the Netherlands. They were
      asked to report on their intention to be open about the diagnosis dementia in
      general and after neuropsychological examination of 90 patients. These answers
      were compared to what was actually said to the 90 patients. The collected data
      have been analyzed mainly qualitatively. RESULTS: Essentially psychologists
      believe that patients need to be informed openly about the diagnosis of dementia.
      In practice nearly all psychologists also intended to mention the diagnosis of
      dementia. However, in about a third of the cases, where the results indicated
      dementia, this was not mentioned openly. Whether or not the diagnosis dementia is
      discussed openly and in which way, appears to depend on the context and the
      clarity of the diagnosis, the wishes and reaction of the carer and whether the
      patient is judged to be able to cope. CONCLUSION: Just like physicians,
      psychologists are not, as a matter of course, open about the diagnosis of
      dementia to their patients. Circumstances appear to guide them more than their
      own opinion about what is appropriate.

PMID- 18637397
TI  - [Screening for depression and anxiety in residential homes for the elderly].
AB  - Elderly persons in residential homes in the Netherlands are at high risk for
      developing major depressive and anxiety disorders. A stepped-care protocol being
      used in a study for vulnerable elderly in the community may also be feasible and
      effective for this group. A pilot study in a residential home in Amsterdam showed
      more problems than expected in screening and motivating the inhabitants for this
      intervention protocol. This article describes the problems in our screening
      procedure. A personal approach, performed by familiar persons, directed at the
      more independent inhabitants is most likely to succeed. The need for research on
      effectiveness and feasibility of evidence based methods in residential care
      remains evident. However, the more vulnerable inhabitants need something else.
      For this group of inhabitants we need to look more closely to the needs and
      possibilities by conducting research using a qualitative design.

PMID- 18637398
TI  - [Primary care in homes for the elderly].
AB  - Dutch GP's (General Practitioners) take care of people living in homes for the
      elderly. The population of these homes is selected on the basis of poor
      functioning on ADL (activities of daily living). We expected to find a group of
      elderly people within these homes that need more complex primary care. We
      describe the characteristics of care for an institutionalized elderly population
      and compare these to the care provided to their independently living peers. The
      design of this study is a matched case-control study in a Dutch General Practice
      in the study period 1/1/1998 to 1/7/2004. Our main results show that the rate of
      cognitive problems is two times, the prevalence of depression even three times
      higher in older people living in a home for the elderly than in those who live
      independently. Locomotory problems are a frequent problem in homes for the
      elderly. Rates of chronic pulmonary problems, atherosclerosis-related diseases
      and urinary tract infection are higher, whereas no significant differences for
      CVA, diabetes and cancer were found. Institutionalized older patients use more
      different types of medication. GP's do not have more contacts with people living
      in a home for the elderly than with older people living independently. We
      conclude that people living in homes for the elderly have complex problems, and
      need special attention for their specific vulnerability. Differences in care are
      not primarily explained by chronic disease but by problems with mobility,
      confusion, depression and cognition.

PMID- 18637399
TI  - [Prevalence of ulcers in Dutch nursing homes].
AB  - INTRODUCTION: Earlier cross-sectional research in the Netherlands has found that
      one out of three nursing home patients has a pressure ulcer. The prevalence of
      other ulcers is unknown. METHODS: In eight nursing homes 2295 patients were
      assessed with the Minimum Data Set (MDS). The mean age of the patients was 82.9
      years (SD 7.4) and 70% was female. One third had severe cognitive impairment and
      only 17% had no or little ADL impairment. RESULTS: Prevalence of pressure ulcers
      was: stage 1: 3,6%; stage 2: 2,5%; stage 3: 1,2%; stage 4: 0,8%. Having a
      pressure ulcer was strongly correlated with ADL dependency: Odds Ratio (OR) 8,4
      for moderate ADL-dependency, and OR 35,4 for severe ADL-dependency. Patients with
      pressure ulcers had more often pain (OR 2,7) and depressive symptoms (OR 2,1).
      Bowel incontinence was significantly correlated (OR 2,6) with pressure ulcers,
      just as the presence of an indwelling catheter (OR 3,2) and the use of diapers
      (OR 2,2), but urinary incontinence was not correlated with pressure ulcers. The
      prevalence of a venous ulcers was 2,6% and 1,7% had a venous ulcer higher than
      stage 1. The combination of foot ulcers and diabetes occurred in 1,2%, the
      combination of a peripheral vascular disease and ulcers in only 0,7%. The use of
      pressure reducing interventions increased with ADL dependency, nevertheless only
      44% of the very dependent patients used these interventions.

PMID- 18637400
TI  - Pharmacodynamics of tubulin and tubulin-binding agents: extending their potential
      beyond taxanes.
AB  - Chemotherapeutic agents that disrupt the assembly or disassembly of microtubules,
      including paclitaxel and docetaxel, are among the most commonly prescribed
      anticancer therapies. However, the utility of taxane-based therapy is limited
      principally by problems with formulation, slow administration, cumulative
      neurotoxicity, and resistance in part through induction of P-glycoprotein. The
      broad-spectrum anticancer activity of taxane therapy has encouraged investigators
      to identify a class of structurally novel microtubulin-stabilizing agents that
      could produce comparable outcomes with fewer problems. Preclinical studies
      indicate that epothilones have a broad spectrum activity in paclitaxel-resistant
      breast cancer models. Several epothilone analogues have displayed promising
      antitumor activity in initial clinical trials. Ixabepilone, an epothilone
      derivative in the later stages of clinical development, has exhibited antitumor
      activity in breast cancers, with or without previous taxane therapy. The most
      common adverse events associated with ixabepilone are reversible sensory
      neuropathy and neutropenia. This review briefly outlines the basic science behind
      microtubule-targeting agents and examines the preclinical studies of several of
      these agents in breast cancer models. Also discussed are results from clinical
      trials of epothilones alone and in combination in patients with breast cancer.

PMID- 18637401
TI  - Options for the treatment of patients with taxane-refractory metastatic breast
      cancer.
AB  - The application of taxane chemotherapy to the treatment of early-stage and
      advanced breast cancer has resulted in significant improvements in disease-free
      and overall survival. As a consequence of these improvements in disease outcome,
      oncologists must face the new challenge of developing additional therapies that
      are effective against taxane-resistant disease and are associated with a
      favorable toxicity profile. This article discusses some of the chemotherapeutic
      options available for the treatment of patients with taxane-resistant metastatic
      breast cancer. Newer formulations of traditional microtubule-stabilizing agents,
      such as albumin-bound paclitaxel, which uses a more favorable vehicle for
      administration compared with conventional paclitaxel, have demonstrated efficacy
      in this setting. Several novel microtubule-targeting agents have been shown to be
      less susceptible to traditional mechanisms of taxane resistance, such as the
      multidrug resistance phenotype associated with increased activity of the P
      glycoprotein drug efflux system and the development of structural changes in
      tubulin. Examples of these therapies include the vinca alkaloids, such as
      vinorelbine and vinflunine; epothilones; and eribulin. Traditional
      antimetabolites, such as gemcitabine and capecitabine, used as monotherapy or
      combination chemotherapy have also shown efficacy in the treatment of patients
      with taxane-resistant breast cancer. A greater understanding of the mechanism of
      drug resistance, as it pertains to taxanes, will enable further development and
      the effective application of chemotherapeutic agents that will circumvent drug
      resistance and result in improvement in breast cancer control.

PMID- 18637402
TI  - Clinical experience with epothilones in patients with breast cancer.
AB  - The search for novel chemotherapeutic agents in the treatment of breast cancer
      with lower susceptibility to resistance mechanisms than current agents has led to
      the discovery of the epothilones and their analogues. Epothilones stabilize
      microtubules in a manner similar to taxanes but are structurally distinct.
      Ixabepilone, an epothilone B analogue, having demonstrated high antimicrotubule
      activity in preclinical studies, has shown notable efficacy in phase II trials in
      patients with early-stage and metastatic breast cancer. Of particular note,
      single-agent ixabepilone is effective in tumors resistant to anthracyclines,
      taxanes, and capecitabine, for which there is currently no recommended therapy.
      Different mechanisms of action and the non-overlapping toxicities of ixabepilone
      with other agents provide the rationale for ixabepilone in combination as a valid
      therapeutic approach. Phase II results assessing ixabepilone in combination with
      capecitabine in anthracycline- and taxane-pretreated patients are promising. The
      investigation of ixabepilone in the neoadjuvant setting has also revealed
      potential biomarkers to predict ixabepilone response. Ixabepilone has
      demonstrated activity in patients with tumors that are estrogen receptor-,
      progesterone receptor-, and HER2-negative. The safety profile throughout the
      trials has been manageable, with peripheral neuropathy as one of the more notable
      adverse events, which has been mostly reversible. A phase III trial comparing
      ixabepilone plus capecitabine versus capecitabine alone demonstrated significant
      prolongation of median progression-free survival and reduction in relapse risk.
      Additionally, other members of the epothilone family, such as patupilone, ZK-EPO,
      BMS-310705, and KOS-862, have demonstrated efficacy against breast cancer in
      phase I clinical trials. Ongoing phase II/III trials continue to assess
      ixabepilone and other members of the epothilone family in breast cancer,
      particularly in combination regimens, as being valid treatment options in
      multidrug-resistant breast cancer.

PMID- 18637403
TI  - Predictive markers of tubulin-targeting agents in breast cancer.
AB  - Microtubules are formed by an equal amount of alpha- and beta-tubulins through a
      dynamic process of polymerization and depolymerization that reaches equilibrium.
      Tubulin-targeting agents affect the microtubule function to disrupt cell shape,
      microvesicle transportation, and spindle formation. The use of tubulin-targeting
      agents, especially the newer agents such as taxanes, has significantly increased
      the response and even survival in patients with many cancers, including breast
      cancer. However, not all patients respond to these agents. Also, most patients
      develop recurrent or progressive disease, especially in the metastatic setting.
      The use of predictive markers of tubulin-targeting agents is therefore needed to
      increase the therapeutic ratio in the selected patient population. However, many
      clinical studies have failed to identify reliable and reproducible clinical or
      biologic markers that serve this purpose. Of the various markers examined, beta
      tubulin III and its related proteins, such as tau, seem to predict the response
      to taxanes in preliminary clinical studies. However, most of these studies are
      limited by many factors such as small sample size, heterogeneous patient
      population, disease stages, and different methods in marker detection. None of
      these markers have been validated by large prospective clinical trials. Since
      tumor cells are driven by many signal transduction pathways, the study of the
      gene expression signature rather than a single gene is more likely to identify
      the ultimate predictive markers of response to tubulin-targeting agents. Gene
      expression profiling and proteomics are in preclinical development and in early
      clinical trials. They will eventually enable us to offer patients tailored
      chemotherapy with the tubulin-targeting agents. Before such predictive markers
      are available, these agents may be considered in patients with good performance
      status and aggressive tumors.

PMID- 18637404
TI  - Illustrated keys to the mosquitoes of Thailand V. Genera Orthopodomyia, Kimia,
      Malaya, Topomyia, Tripteroides, and Toxorhynchites.
AB  - Illustrated keys for the identification of the fourth-instar larvae and adults of
      species representing six genera of mosquitoes in Thailand are presented, along
      with information about the geographic distribution of the species and the
      habitats occupied by their immature stages. Fifty-nine species belonging to
      genera Orthopodomyia, Kimia, Malaya, Topomyia, Tripteroides, and Toxorhynchites
      are recognized. Topomyia argyropalpis, To. bifurcata, To. gracilis, To.
      spathulirostris, To. tenuis, To. tipuliformis, and To. vijayae are included as
      new country records, and ten undescribed species, four in Topomyia, four in
      Toxorhynchites, and two in Tripteroides, are recognized.

PMID- 18637405
TI  - Bilingualism: not as straightforward as you might think.

PMID- 18637406
TI  - Performance of bilingual speakers on the English and Spanish versions of the
      Hearing in Noise Test (HINT).
AB  - This study compared the performance of bilingual participants on the English and
      Spanish versions of the Hearing in Noise Test (HINT). The participants were
      divided into an early bilingual (EB) group and a late bilingual (LB) group based
      on age of second-language acquisition. All participants acquired Spanish as their
      first language (L1) and English as a second language (L2). Care was taken to
      ensure that all participants demonstrated at least a "good competence level" for
      self-rated speaking, understanding, reading, and writing skills in both English
      and Spanish. Results revealed superior performance on the Spanish HINT versus the
      English HINT in both quiet and in noise for both groups of participants.
      Significant differences in performance were noted for the EB versus the LB
      participants. A number of possible explanations for superior performance in L1
      are provided, and implications for educating students in their L2 are discussed.

PMID- 18637407
TI  - Distribution of thetaY226 in a clinical population.
AB  - ThetaY (thetaY) is the phase angle between the admittance vector and the
      conductance component in an acoustical system. It is determined by the relative
      contributions of the system's conductance and susceptance. The magnitude of the
      admittance vector has received almost exclusive attention in clinical admittance
      measurements. The phase angle, providing information on the relative contribution
      of energy-dissipating and energy-storing components, has been largely overlooked.
      One hundred and ninety-five clinical records obtained over a five-year period
      were used to investigate the distribution of thetaY and its relationship to other
      tympanometric variables. The results show that thetaY has a reasonably
      symmetrical distribution and is not strongly related to other tympanometric
      variables. The data suggest that thetaY may account for a different subset of the
      total variance than more commonly measured variables. ThetaY appears to meet the
      criteria of independence and distribution, justifying further study to evaluate
      its clinical utility.

PMID- 18637408
TI  - Hemodynamic differences in children with dichotic listening deficits: preliminary
      results from an fMRI study during a cued listening task.
AB  - Functional magnetic resonance images were acquired while children with and
      without dyslexia identified incongruous words embedded within fairy tale segments
      in a quasidichotic listening task. All children produced greater activation in
      the left hemisphere than in the right hemisphere during the binaural separation
      listening task. Children with dyslexia, who had a higher incidence of a dichotic
      left ear deficit from prescanning behavioral tests, produced fewer hits and more
      misses than control children while monitoring their left ears in the scanner.
      Control children produced stronger left hemispheric activation for ipsilateral
      left ear input than right hemispheric activation for ipsilateral right ear input,
      but ipsilateral activation patterns in children with dyslexia were symmetrical.
      Children with dyslexia who monitored their right ears first produced the lowest
      left hemispheric activation overall, suggesting that priming of the right ear may
      have inhibited the ability of children with a left ear deficit to adequately
      identify target words presented toward their left ears while in the scanner.

PMID- 18637409
TI  - Observations on mastoid versus ear canal recorded cochlear microphonic in
      newborns and adults.
AB  - The cochlear microphonic (CM) may play an important role in the diagnosis of
      auditory neuropathy (AN) in newborns. However, since the CM tends to mirror the
      waveform of the acoustic stimulus, conscientious recording methodology must be
      applied to separate true response from artifact. The difficulty in achieving this
      separation has limited the clinical usefulness of the CM. In an effort to call
      attention to the importance of recording protocol when measuring the CM, the
      present study was designed to optimize CM recordings in humans by investigating
      the following parameters: (1) secondary minus electrode recording site (mastoid
      versus ear canal [EC]), (2) stimulus parameters, and (3) grounding and shielding
      conditions. Normative data were collected in full-term newborns (n = 7) and
      adults (n = 4) with no known risk factors for cochlear or retrocochlear
      pathology. Results suggest that the CM is easier to separate from stimulus
      artifact using an EC electrode and toneburst stimuli. In addition,
      electromagnetic shielding and grounding of the electrode cables and the acoustic
      transducer were effective in reducing and/or eliminating stimulus artifact.
      Results from this normative study may be helpful in improving the diagnostic
      utility of the CM in AN and other hearing-related disorders.

PMID- 18637410
TI  - Development of a clinical test of musical perception: appreciation of music in
      cochlear implantees (AMICI).
AB  - The purpose of this study was to develop a test to assess the ability of persons
      with cochlear implants (CIs) to interpret musical signals. Up to this time, the
      main direction in outcomes studies of cochlear implantation has been in relation
      to speech recognition abilities. With improvement in CI hardware and processing
      strategies, there has been a growing interest in musical perception as a
      dimension that could improve greatly users' quality of life. The Appreciation of
      Music in Cochlear Implantees (AMICI) test was designed to measure the following
      abilities: discrimination of music versus noise; identification of musical
      instruments (from a closed set); identification of musical styles (from a closed
      set); and recognition of individual musical pieces (open set). The first phase of
      the study was test development and recording. The second phase entailed
      presentation of a large set of stimuli to normal listeners. Based on phase 2
      findings, an item analysis was performed to eliminate stimuli that were confusing
      or resulted in high error rates in normals. In phase 3, hearing-impaired
      participants, using cochlear Implants, were assessed using the beta version of
      the AMICI test.

PMID- 18637411
TI  - Effects of interaural time and level differences on the binaural interaction
      component of the 80 Hz auditory steady-state response.
AB  - The auditory steady-state evoked response (ASSR) is a scalp-recorded potential
      elicited by modulated sounds or repetitive transient sounds presented at a high
      rate. The binaural interaction component (BIC) of the ASSR equals the difference
      between the response to binaural stimuli and the sum of the responses to a
      monaural stimulus presented to the left ear and the right ear. This study
      examined the effect of the interaural time (ITD) and level (ILD) difference on
      the BIC of the 80 Hz ASSR. Sixteen human participants with normal hearing were
      tested. The ITD and ILD were varied from -1.6 to +1.6 msec and from 0 to +12 dB,
      respectively. The ITD function of the BIC showed a "V" shape, with a 0 value of
      BIC at ITD 0 msec and a positive BIC at ITD +0.8 to +1.6 msec. For ILD
      conditions, the BIC displayed negative values, and its amplitude became more
      negative as the ILD was increased. The results indicate that the ITD and ILD may
      be processed by different groups of binaural neurons in different pathways. It is
      suggested that the 80 Hz ASSR provides an objective means for evaluating binaural
      functions in patients such as those with central auditory processing disorders.

PMID- 18637412
TI  - Filoviruses. A compendium of 40 years of epidemiological, clinical, and
      laboratory studies.

PMID- 18637413
TI  - [Four hands surgery in endoscopic sinus surgery--our experience].
AB  - Endoscopic surgery in chronic sinusitis became a gold standard since Stammberger
      and Kennedy describe there technique in '80 s. During last 20 years an enormous
      progress has been done in that field. Tumors of the nose and paranasal sinuses
      became a target for endonasal surgery, alternatively to open approaches. This
      surgery is more bloody, needs more tools, so the next step was to introduce the
      second surgeon into endoscopic sinus surgery and the four hands technique has
      born. Three models of four hands technique are present in the literature. Since
      November 2006 at the ENT department at Medical University in Poznan 24 patients
      have been operated on with this technique out of wich 12 suffered from tumors and
      12 patients have been diagnosed with chronic sinusitis. This paper describe the
      surgical technique and our experience based on this 24 operations.

PMID- 18637414
TI  - [In the case of "difficult" tracheotomy].
AB  - Difficulties from open surgical procedures are common. The severity and frequency
      of these occurences depends on several factors: anatomic, physiologic, kind of
      local patology and skills and experience of operator. The incidents of undesires
      outcomes during tracheostomy can not be exactly predictet because interactions of
      the above issues. This paper consider some of difficulties observed in our
      department from January 2000 to July 2007. Tracheotomy is usssually a safe
      procedure, but complication ranging could be high in the following conditions:
      morbid obesy, a short and thick neck, cervical stiffness, tumors and
      infiltrantions of the neck, thyroid gland tumors.

PMID- 18637415
TI  - [Transpalatal approach for juvenile angiofibroma].
AB  - INTRODUCTION: Juvenile nasopharyngeal angiofibromas (JNA) are highly vascular,
      locally invasive tumours which originate in the sphenopalatine foramen. Several
      surgical approaches are described for this tumour. The aim of this study was to
      evaluate the transpalatal approach for juvenile angiofibroma. MATERIAL AND
      METHODS: In a group of 22 patients with JNA transpalatal approach was employed. A
      retrospective patients notes review was done. Extension of tumour, complications
      of surgery and recurrences were analyzed. RESULTS: In 17 patients the tumour was
      confined to the nasal cavity and the nasopharynx. In 5 patients the tumour
      invaded the sphenoid sinus. No complications were observed after surgery. Two
      (9%) patients had recurrence. CONCLUSION: Transpalatal approach is best suited to
      small tumours (Andrews grade I and II) limited to the nasopharynx, nasal cavity
      and sphenoid sinus.

PMID- 18637416
TI  - [Juvenile angiofibroma in adults].
AB  - INTRODUCTION: Juvenile nasopharyngeal angiofibroma is a benign lesion which is
      characterized by three distinctive features: it occurs only in one sex, one
      period of age and in one location in the organism. MATERIAL AND METHOD: Basing on
      literature and our series concerning 36 patients treated during 50 years, we
      present atypical cases of angiofibroma. All of them accomplished
      patomorphological and clinical criteria of this neoplasm, beside of age and sex.
      Our study reports three cases of angiofibroma, two of them concerning males aged
      34 and 49 years and one case - female aged 68 years. RESULTS: Clinical and
      radiological investigation revealed tumor in typical location - posterior part of
      nasal cavity and nasopharynx in all patients, with it's extension to paranasal
      sinuses in 2 cases. The preoperative supraselective embolisation was performed in
      two cases. Results of histological examination of our atypical cases were similar
      as in angiofibromas observed in adolescents. All patients were treated surgically
      by different approaches according to tumor's extension. A recurrence has occurred
      in one patient after nearly two years and was treated successfully by
      reoperation. In two other patients no recurrence was observed during follow-up.
      CONCLUSION: Our study concerning the occurrence of juvenile angiofibroma in
      adults, also in female, as the other observations from literature may constitute
      some remarks in discussion about the pathogenesis and clinics of this tumor.

PMID- 18637417
TI  - [Laryngeal leiomyosarcoma in clinical cases of the Otolaryngology Departament in
      the University Hospital of Krakow].
AB  - INTRODUCTION: Leiomyosarcoma is a malign neoplasm coming from the non-epithelial
      tissue. It rarely developes in the larynx. 0,5-1% of all of the neoplasm of the
      larynx is leiomyosarcoma. It usually developes in the age of 40-70 and mostly
      effects men. AIMS: Improvement of the therapy of patients with leiomyosarcoma of
      the larynx. MATERIAL AND METHODS: The analysis of the medical documentation of
      the 5 patients with the diagonosis of leiomyosarcoma laryngis treated in
      Otorhinolaryngologic Clinic UJ in 1996-2006 was performed. The procedures and
      effects of the therapy were analized. RESULTS: In this particular period of time
      11 patients was operated because of the sarcoma of the larynx. In this group
      there were 5 cases of leiomyosarcoma, 4 cases of chodrosarcoma and 1 case of
      agniomyxofibrosarcoma and 1 case of sarcomy synoviale. CONCLUSIONS: On the basis
      of the material of the Clinic the frequency of these tumors was estimated and the
      therapeutic procedure including widening of the surgical indications for the
      partial laryngectomy and narrowing the indications for nodular surgery of the
      neck was proposed.

PMID- 18637418
TI  - [The new insight into the pathogenic unity of the upper and lower airways].
AB  - Between the upper and the lower respiratory tracts exists a link. Numerous
      epidemiological, immunological studies and clinical observations suggest the
      pathogenic unity of the upper and lower airways. The most important observations
      regarding the nose-lung interaction is rhinitis and asthma. The inflammatory
      process in the nose is the same as in the bronchi, clinically defined as
      rhinosinusitis, nasal polyps, asthma, bronchial hyperreactivity, allergy, viral
      infections. The strict link between the rhinosinusitis and asthma implies new
      possibility of influencing one of the two complaints by treating the other one
      with an integrated therapy (pharmacotherapy, endonasal microsurgery).

PMID- 18637419
TI  - [Results of treatment in patients with paranasal sinus carcinoma. Analysis of
      prognostic factors].
AB  - Analysis was based on the results of successful and unsuccessful treatment of 137
      patients with paranasal sinus cancer at the Oncology Centre in Warsaw between
      1987-2002. Patients with clinical stages T3 and T4 constituted 87% of cases (110
      patients). Radical treatment was performed on 84 patients. Five-year overall
      survival in 137 cases amounted to 27%; and survival without recurrence was 24%.
      Five-year overall and recurrence-free survial among patients treated with surgery
      and radiotherapy were 36% and 32% retrospectively. Multivariate analysis of 61
      patients with complete data, who were treated with radical surgery and
      radiotherapy, emphasized the influence of prognostic factors on survival. A worse
      prognosis correlated with advanced locoregional T and N stage. It is evident that
      total dose greater than 6000 cGy had a clear impact on the results of treatment.
      It was also shown that planning with the manually and hand-measured isodoses
      impacted negatively on the survival in comparison with 2D and 3D planning.
      Analysis of recurrence-free survival showed that metastatis to the lymph nodes,
      and a manually-planned treatment method, had a negative impact on the results of
      treatment. It is asserted that local recurrences are the main cause of failure in
      cases treated with surgery and radiotherapy.

PMID- 18637420
TI  - [Value of angiography and embolisation in treatment of head and neck vascular
      malformations at Otolaryngology Department, Poznan University of Medical
      Sciences, Poland].
AB  - Angiography is an invasive, radiological investigation of vascular system. It
      plays an important role within variety of diagnostic tools in head and neck
      pathologies. In selected cases with well defined tumor supply vessels,
      angiography may be combined with intravascular obliteration. This possibility
      widen indications, which comprise diagnostic arteriographies - visualization of
      blood supply and extension of vascularization; therapeutic and diagnostic
      arteriographies - palliative or radical in character, dependent on pathology; and
      therapeutic angiographies as adjuvant therapy prior to surgical treatment.
      Authors present their experience with endovascular techniques application in head
      and neck pathologies. Material comprised 59 angiographies performed in patients
      treated at Otolaryngology Department at Poznan University of Medical Sciences
      between 2000-2007. In conclusion authors emphasize advantages and disadvantages,
      as well as, the role of the endovascular treatment in head and neck surgery.

PMID- 18637421
TI  - [Chronic otitis media as an introduction to intracranial otogenic complications].
AB  - INTRODUCTION: Otogenic intracranial complications are rare. Misdiagnosed and
      untreated can be dangerous for health and life. They should be always kept in
      mind. AIM: We discuss patients in whom defects of skull base were observed during
      operation. These defects can lead to serious intracranial complications. MATERIAL
      AND METHODS: We analyse patients with chronic otitis media operated in our
      department between 2004-2006. 250 operations on ears were performed in that
      period of time. We discuss patients with intracranial otogenic complications and
      patients in whom defects of skull base were noticed by chance during operations.
      RESULTS: Defects of skull base were observed in 24 cases. Intracranial
      complications were in 3 patients. 1 patiens died because of abscess of
      cerebellum, others were treated with good distant effect. Used methods of
      reconstruction were effective, we observed no discharge of cerebro-spinal fluid
      and no other intracranial complications. CONCLUSIONS: It exists group of patients
      with chronic otitis media that have asymptomastic defects of cranial fossa. These
      defects can be responsible for intracranial complications. MRI and TC are very
      important in preoperative diagnostics.

PMID- 18637422
TI  - [Role of IFN-gamma and TNF-alpha in etiology of nasal polyps--initial studies].
AB  - OBJECTIVE: Nasal polyposis is a chronic inflammatory disease of the nasal mucosa.
      The pathogenesis of nasal polyps is still not entirely known and has been debated
      for many years. The aim of the present study was to evaluate the expression of
      interferon gamma and TNF-alpha secreted by Th1 lymphocytes and to analyze their
      role in the etiology of nasal polyps. METHODS: 12 patients with nasal polyposis
      were selected - 6 of them allergic and 6 non-allergic. Patients with allergy were
      distinguished from those without allergy on the basis of positive allergy skin
      tests to dust and serum levels of IgE. Blood sample was obtained from patients
      and examined for the expression of IFN-gamma and TNF-alpha by intracellular
      staining procedure after stimulation with PMA/ionomycin and allergen. RESULTS:
      Negative correlation was found between expression of IFN-gamma and TNF-alpha
      after PMA/ionomycin stimulation and allergen stimulation (p > 0,05). Statistical
      analysis of two groups of patients demonstrated that no significant differences
      in the cytokine expression in allergic versus non-allergic patients were observed
      although mean value of IFN-gamma and TNF-alpha were lower in allergic patients in
      comparison to non-allergic (p > 0,05). We didn't observed any correlation between
      expression of INF-gamma and TNF-alpha and: coexistence of bronchial asthma,
      allergy to aspirin and local corticosteroid treatment. In patients with recurrent
      polyposis the expression of INF-gamma was significantly lower (p = 0,05).
      CONCLUSION: This research suggests that IFN-gamma and TNF-alpha play a role in
      the pathogenesis of nasal polyps but the allergic mechanism may not play a
      fundamental role in this process. It needs further investigations.

PMID- 18637423
TI  - [Expression Fas and FasL antigen protein of lymphocytes T and B in hypertrophied
      adenoid in children with otitis media with effusion].
AB  - INTRODUCTION: Apoptosis of lymphocytes can be induced by different factors mainly
      however the activation of antigen Fas (CD95) and his ligand FasL (CD95L) route.
      Apoptosis induced by Fas-FasL has large significance in elimination of
      lymphocytes T in final phase immune response designate AICD (activation induced
      cell death). Lymphocytes B undergo apoptosis induced by Fas-FasL in germinal
      center, which has special meaning in elimination of cells about low specificity
      and weak affinity of receptor BCR ( B-cell antigen receptor). AIM OF STUDY: The
      aim of this study was evaluation of percentage of apoptotic lymphocytes and
      expression of Fas and FasL in CD4+, CD8+, CD19+ lymphocytes in hypertrophied
      adenoid and hypertrophied adenoid and otitis media with effusion. METHODS:
      CD4+Fas+, CD8+Fas+, CD19+Fas+CD4+FasL+, CD8+FasL+, CD19+FasL+ cells subpopulation
      were identified using monoclonal antibodies and flow cytometry method. RESULTS:
      The percentage of lymphocytes CD4+ Fas+, CD8+Fas+, CD19+Fas+ was higher in
      hypertrophied adenoid and otitis media with effusion compored to the control
      group. Their was no significant difference the percentage CD4+ Fas+, CD8+Fas+,
      CD19+Fas+CD4+FasL+, CD8+FasL+, CD19+FasL+ in hypertrophied adenoid and otitis
      media with effusion then the control group. The percentage of apoptotic
      lymphocytes was higher in hypertrophied adenoid and otitis media with effusion
      compored to the control group. CONCLUSIONS: The susceptibility the individual
      subpopulation of lymphocytes in hypertrophied adenoid seems to influence on
      change of relations of quantitative lymphocytes and upset the immunological
      function of tonsils which can influence on course otitis media with effusion at
      children.

PMID- 18637424
TI  - [Myringoplasty in children--success factors].
AB  - OBJECTIVE: Myringoplasty is successfully performed in children since many years.
      However still considerable controversy surrounds the subject of proper timing of
      surgery and other factors influencing the success rate. The aim of this study was
      to assess the results of myringoplasty in children and to determine which factors
      influence the postoperative results. MATERIAL AND METHODS: Retrospective study of
      the anatomic and functional results of 82 consecutive myringoplasties performed
      in children between 1996-2004. Seventy one children (mean age 13 +/- 2,9 years,
      range 6,4-18 years) who had undergone myringoplasty because of central
      perforation or retraction pocket in the pars tensa were evaluated. All of the
      children underwent myringoplasy using endaural or post-auricular approach and
      underlay technique. Temporalis fascia, perichondrim or cartilage were used as a
      graft material. The results were assessed on the basis of otoscopic and
      audiometric examination pre and postoperatively. Following factors have been
      analyzed to assess their influence on the success rate: age, size and site of
      perforation, status of the operated ear (dry/discharging), status of the
      contralateral ear. RESULTS: Closure of the perforation was achieved in 91,5% of
      children. A good anatomic outcome was observed in 87,8%. The Air Bone Gap between
      0-20 dB was observed in 95,6% of patients. Age below 10 years was found to
      significantly affect the results of surgery. The rate of success was lower in
      cases with pathological process in the contralateral ear but the difference was
      not statistically significant. CONCLUSIONS: Myringoplasty with underlay grafting
      of the fascia temporalis or perichondrium gives good anatomic and functional
      results in children. The results are significantly worst in children below 10
      years of age. Pathological changes in the contralateral ear influence the risk of
      an abnormal postoperative tympanic membrane.

PMID- 18637425
TI  - [Treatment of the nasal septal hematoma and abscess in children].
AB  - OBJECTIVES: Estimation of the treatment of the nasal septal hematoma and abscess
      after injury was performed. MATERIAL AND METHODS: In 1998-2005 in Department of
      Otolaryngology Children's Hospital in Warsaw 2500 children after nasal injury
      were examined. Nasal septal hematoma and abscess were diagnosed in 22 (0,9%).
      They were reviewed retrospectively and some of them were examined 1-8 years
      after. RESULTS: In 22 children with nasal septal hematoma and abscess no
      complication were observed during treatment. In 12 children examined 1-8 year
      after treatment 1 child developed saddle nose deformity (qualified to
      observation) and 1 child developed nasal septum deformities with nasal
      obstruction (qualified to septoplasty). CONCLUSIONS: Complex treatment of nasal
      septal hematoma, drainage of the hematoma with septoplasty and reduction of
      fracture of the nose, makes good functional and cosmetic effect. Drainage of the
      nasal septal abscess with antibiotic prevent the early complications but it isn't
      enough functional and cosmetic effect in the future.

PMID- 18637426
TI  - [Tinnitus diagnosis and treatment on the basis of our experiences].
AB  - INTRODUCTION: The aim of the study was to analise tinnitus diagnosis and
      treatment on the basis of our experiences. MATERIAL AND METHODS: 137 patients
      hospitalizated in Otolaryngology and Laryngological Oncology Clinic because of
      tinnitus (88 women - 64% and 49 men - 35,8%) were included to the study. The
      diagnostic procedures were unified that enabled put forward correct diagnosis.
      After history and otoscopy, detailed audiologic diagnostic procedures (pure tone
      audiometry, suprathreshold audiometry, speech audiometry, acoustic immittance
      measures, auditory brainstem responses) were taken. Electronystagmography and
      videonystagmography, tinnitus loudness match, head and neck radiologic
      examinations supplemented diagnostic procedures. Alternative tinnitus treatment
      options were applied. RESULTS: Study confirmed that tinnitus is the most frequent
      in patients above 50 years old (67,8% of participants). Tinnitus frequently
      coexist with bilateral sensorineural hearing impairment (69,1% of participants).
      40,1% from asalysed group of patients complained of tinnitus of medium
      frequencies and 30,6% of patients complained of high frequency tinnitus. 42,3% of
      participants suffered from vertigo. CONCLUSIONS: The risk of tinnitus increases
      in patients above 55 years old that suffer from metabolic conditions and cervical
      spondylosis. Tinnitus frequently coexist with bilateral sensorineural hearing
      impairment and are bilateral or they are noticeable in better hearing ear. The
      most beneficial to tinnitus is causal and symptomatic treatment with several
      methods application.

PMID- 18637427
TI  - [Assessment of voice in patients with Reinke's oedemas treated with laser
      microsurgery].
AB  - This investigation was undertaken for perceptual and acoustic analysis of voice
      in patients with Reinke's oedemas treated with laser microsurgery. Material of
      the study included 45 patients in the age of 23 to 65 presenting to Foniatric
      Clinic with dysphonia in Reinke's oedemas. Patients were divided into 3 groups
      according to Yonakawa's classification of Reinke's oedemas. All patients were
      treated with CO2 laser microsurgery. Voice assessment was made subiectively with
      GRBAS scale and objectively using multidimensional voice parameters analysis
      (MDVP). The examination was undertaken preoperatively and 4 weeks after
      operation. The results of our study show relationship between quality of voice
      after surgery and the stage of evolution of Reinke's oedemas according to the
      applied classification.

PMID- 18637428
TI  - [Analysis of specificity and sensitivity of Polish "Universal Newborn Hearing
      Screening Program"].
AB  - INTRODUCTION: Polish National Universal Hearing Screening Program (PNPUHS) has
      got three-level structure. Audiology Outpatient Clinic in The Childrens' Memorial
      Health Institute in Warsaw is a center of the second and the third level.
      Newborns are referred to us from neonatal units, the first level in the program.
      We found that referred children, both with unilateral as well as bilateral
      referral rating in TEOAE, show a high proportion of false positive results. AIM:
      To analyze a diagnostic process of healthy neonates referred to our Audiology
      Outpatient Clinic with referral rating in one and both ears measured by TEOAE in
      2005 and 2006. Assessed parameters include: attendance of patients to further
      diagnostics tests, with respect to their results, specificity and sensitivity of
      methods: TEOAE, DPOAE, analysis of final diagnoses of hearing loss. PATIENTS:
      1764 infants without risk factors of hearing loss, aged from one to six months
      referred with referral rating in one or both ears in TEOAE. METHODS: Diagnostics
      methods include: otoscopy, DPOAE, AI, BOA. Incorrect results are indication for
      ABR examination, if not conclusive ASSR. Collected data were statistically
      analyzed by chi-squared test and Czupurow and V-Cramer coefficient. RESULTS: 998
      (56,5%) of 1764 examined children passed DPOAE. Only 512 (66,8%) of remaining 766
      neonates carried on further investigations. Diagnosis of hearing loss was made in
      449 patients (25%), including 320 (71%) with bilateral and 129 (29%) with
      unilateral involvement. Sensorineural hearing loss was detected in 274 children
      (61%), conductive in 161 (35,8%), and mixed in 14 patients (3,1%). Global PNUHSP
      specificity are 95,45% and sensitivity results are 95,08% respectively. Although
      in our Audiology Outpatient Clinic, sensitivity rate of TEOAE and DPOAE is 94,5%,
      and 94,4% respectively, the specificity rate of TEOAE appeared to be 36,9% and of
      DPOAE 79,7%. CONCLUSIONS: Universal newborn hearing screening program permit
      early diagnosis and intervention in neonates and infants before 6th month of age.
      High rate of specificity and sensitivity characterizes the Polish Program. Low
      rate of specificity detected in our outpatient clinic indicates the necessity to
      effect and cost analysis in neonatal units. Comparison of two groups with
      bilateral and unilateral referral rating in screening shows that higher number of
      patients follow diagnostic process from the group with bilateral incorrect
      results, more diagnoses of hearing loss was established in this group as well.

PMID- 18637429
TI  - [Rectal adenocarcinoma metastasis to the facial skin--case report].
AB  - INTRODUCTION: Carcinoma of the large intestine is a common and relatively well
      known neoplastic malignancy of the digestive tract. In a very few cases its
      spread seems unpredictable and can cause a distant metastasis to head and neck
      region. MATERIAL AND METHODS: A 58 years old patient was admitted to the ENT
      Department because of an exulcerated tumour mass of the left mental and buccal
      region. 9 months earlier he underwent anterior resection of rectum due to
      carcinoma. Histopatological examination of specimen from the facial skin lesion
      revealed adenocarcinoma cells. Radiological findings suggested isolated character
      of lesion. The patient was treated by surgery and chemotherapy. Wide excision of
      tumour mass with partial mandibulectomy was performed and the tissue defect
      reconstructed with a pectoralis major musculocutaneous flap. A postoperative
      chemiotherapy with FA and 5-FU followed the surgical procedure. Regardless of the
      first promising results of the oncological treatment the patient died eight
      months later. RESULTS AND CONCLUSIONS: We present this case report as an example
      of an unusual and rare secondary malignancy of head and neck, emphasizing the
      interdisciplinary character of oncological treatment and the role of oncological
      vigilance on every step of diagnosis.

PMID- 18637430
TI  - [Chondroma of the larynx].
AB  - Chondroid tumors of the larynx are extremely rare and their develope and symptoms
      are difficult to diagnosis. The importance of well radiological diagnosis prior
      chirurgical treatment of chondroid tumors of the larynx is empasised.
      Conservative surgical management when possible, is advocated to preserve the
      larynx. We presented a case of chondroma of cricoid cartilage developing in 49
      year old woman with 4 year history of hoarsness, treated by surgical management -
      laryngofissure. During 36 months follow up no reccurency is observed. In the
      paper review of literarature is presented.

PMID- 18637431
TI  - [Glottis morphology and perceptive--acoustic characteristics of voice and speech
      in patients with rheumatoid arthritis].

PMID- 18637433
TI  - [Sinobronchitis--historical aspect].
AB  - There is evidence that a link exists between the upper and lower respiratory
      tracts. During the last fifty years many clinical observations has lead to a new
      pathogenic view of rhinosinusitis and asthma defined as Sinobronchial Syndrome.
      The inflammatory process in the nose and bronchi explains some of the complex
      interactions among different clinical diseases, such as rhinosinusitis, asthma,
      bronchial hyperresponsiveness and viral infections.

PMID- 18637434
TI  - [The analysis of the admissions to the laryngological emergency service in
      Otolaryngology Department of Warsaw Medical University].
AB  - OBJECTIVE: The aim of our work was to carry out an qualitative analysis of the
      all cases delt with in otorhinolaryngological emergency unit throughout one year.
      The information gathered and observations made can result in the valid grounds
      for streamlining of otorhinolaryngological emergency services in the future.
      RESEARCH DESIGN AND METHODS: We examined the medical documentation of 7930
      subjects (3.972 females and 3.958 males, of the average age 42 years), who
      appeared in the otorhinolaryngological emergency unit of SP CSK AM in Warsaw from
      the 1th of January to the 31th of December 2006. RESULTS: The actual emergency
      cases accounted for 40% of all cases. The most common were: injuries (12.80%),
      epistaxises (13.11%), foreign bodies (5.11%). The rest of the cases did not need
      the summary intervention on emergency admission. These were mostly: ear
      inflamations (21.32%), upper respiratory tract infecions (10.77%), cerumen in the
      external ear (8.98%). In 2006, 5,51% of all cases were admitted to the
      otorhinolaryngological ward and up to 5.22% sent to other specialists.
      CONCLUSIONS: The majority of the cases delt with in the otorhinolaryngological
      emergency unit did not need the immediate intervention. A part of these was not
      within the competence of the otorhinolaryngologist. The high proportion of such
      patients can prolong the time of anticipation for highly specialised aid in the
      states of real threat to human's life and health and cause other damages that can
      be harmful to the pacient himself.

PMID- 18637435
TI  - Diffuse idiopathic skeletal hyperostosis inducted stridor and dysphagia.
AB  - Diffuse Idiopathic Skeletal Hyperostosis (DISH) is a condition characterized by
      calcification and ossification of soft tissues, mainly ligaments and enthesis.
      Dysphagia is the commonest complaint, stridor secondary to osteophyte compression
      has rarely been documented. The osteophytes may cause symptoms by mechanical
      compression or by inducting inflammatory reaction. When an upper segment of the C
      spine is involved, particular C3 - C4 level, the larynx may be affected. This
      could be result of hoarseness, stridor, laryngeal stenosis and obstruction.
      Sometimes vocal fold paralysis may result from injury to the recurrent laryngeal
      nerve. Treatment of the breathing problems required first on stabilization the
      airway with tracheostomy. Next step is osteophysectomy which generally relief
      patients from symptoms.

PMID- 18637436
TI  - [Ways of treatment of non-malignant laryngeal tumors in older patients--laryngeal
      amyloidosis].
AB  - INTRODUCTION: Amyloidosis' are the heterogeneous group of diseases characterized
      by extracellular accumulation of secondary protein structures causing progressive
      disturbances of the organs. Amyloid deposits are localized mainly in the tissues
      of parenchymal origin (spleen, kidneys, liver) and as far as otorhinolaryngologic
      organs are concerned the primary pathological process is rare. AIM: The case
      presentation and the diagnostic and surgical procedure analysis with the
      assessment of the effects of therapy in patients in elderly age with amyloidosis
      of larynx. MATERIAL AND METHODS: A 82-year-old patient with a tumor of the larynx
      hospitalized in Otorhinolaryngology Clinic in Cracow. The first symptom of the
      pathologic process in this patient was an increasing laryngeal dyspnoe and the
      preliminary macroscopic assessment based on indirect laryngoscopy and endoscopy
      suggested the proliferative process from the group of non-epithelial neoplasm.
      RESULTS: In this case tracheotomy was performed and four days later the
      pathologic change was endoscopically removed from larynx. The improvement of the
      local state was achieved which enabled to decannulate the patient. CONCLUSIONS:
      The amyloid deposits in otorhinolaryngologic organs are rare. Isolated changes in
      larynx suggesting malign neoplasm are the benign changes but on account of the
      specificity of the organ they can be a real threat to life.

PMID- 18637437
TI  - [HIV infected child in otolaryngological practice].
AB  - The authors present material about 12 HIV infected children at the age between 0
      and 18 years observed and treated in Department of Infectious Diseases Medical
      University of Gdansk in the period between 1991 till 2006. Retrospectively
      medical records of 4 of them currently undergoing observation and treatment have
      been analyzed taking into consideration: ways of HIV infection, applying the
      possible retroviral profilactic to a mother and a child, the damaging o of
      immunological condition in the period of observation and treatment as well as the
      possible head and neck changes. The authors come to conclusion that changes in
      oral cavity may be the first symptom of child HIV infection and in the oral
      candidiasis symptoms the possibility of HIV infection should be taken into
      account.

PMID- 18637438
TI  - [Risk of distant metastases after postoperative radiation therapy for locally
      advanced laryngeal cancer].
AB  - PURPOSE: To evaluate the prognostic factors for the risk of distant metastases
      after postoperative radiotherapy for laryngeal cancer. MATERIAL AND METHODS:
      Medical records of 267 patients cancer treated between 1997 and 2003 were
      analyzed. All pts had locally advanced squamous cell laryngeal cancer treated
      with surgery and postoperative radiotherapy. Metastasis Free Survival was
      analyzed using Kaplan-Meier method. A multivariate Cox proportional hazard model
      and logistic regression model was used to evaluated influence of the following
      variables on MFS and the ultimate risk of metastases: age, sex, localization, TN
      stage, HGB before and at the end radiotherapy, total radiation dose, dose per
      fraction, overall treatment time, interval surgery-radiation time, pathological
      margins and positive nodes in surgical specimen. RESULTS: The crude incidence of
      distant metastases was 12% (33/267 pts). One year, 3-year, 5-year actuarial
      metastases free survival were 95%, 85% and 84% respectively. The lungs and bones
      were the most common sites of metastases (58% and 33% respectively), whereas
      metastases to liver (6%) and brain (3%) were rare. Localization of cancer
      (glottic vs. supraglottic) and number of positive lymph nodes at pathological
      staging significantly and independently affected MFS. CONCLUSIONS: Number of
      positive lymph nodes in pathological specimen and site of primary cancer (glottic
      vs. supraglottic) significantly and independently predict a risk of distant
      metastases in combined modality treatment for laryngeal cancer.

PMID- 18637439
TI  - [Mitochondrial DNA mutations in the pathogenesis in the head and neck squamous
      cell carcinoma].
AB  - Data reported until today suggested a pivotal role of nuclear DNA mutations in
      the process of carcinogenesis. Recently more and more authors claim that
      disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA
      have been reported in many cancers of head and neck region. Mitochondrial D-loop
      has been proven to be mutation hot - spot with majority of mutations in the
      positions 303 to 315 of poly-C tract. Data show that 37% of patients with
      premalignant lesions and 62% with carcinoma in situ are positive for mtDNA
      mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6
      were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured
      in similar number of cases. Neoplastic cells undifferentiation and disease
      progression is accompanied by multiplication of mtDNA number and increased mtDNA
      content. mtDNA content corellates with the stage of the disease. mtDNA mutations
      faciliate cell proliferation and inhibit apoptosis by increasing the production
      of ractive oxygen species (ROS). Cells harbouring mutated mtDNA have increased
      proliferation rate, as increased ROS concentration may act as an endogenous
      growth factor.

PMID- 18637440
TI  - [9-years results of the functional endoscopic sinus surgery in ENT department in
      Poznan--from microscope to four hands technique].
AB  - Surgical procedure is used in chronic rhinosinusitis and aims at restoring proper
      drainage and ventilation. For this reason the surgery of this region is referred
      to as functional and in English literature is termed as FESS. It supplanted
      classical method of Caldwell-Luc or Denker. In the study nine years experience in
      the Department of Otolaryngology, Head and Surgery University of Poznan in the
      treatment of chronic sinusitis has been presented. 1463 patients treated with
      FEES were analyzed. Moreover, the method of selecting patients for the surgery,
      the diagram showing surgeries performed step by step as well as a list of various
      surgeries and intraoperative complications were presented. This work is the first
      part of the study. In the other part the results of the treatment based on the
      questionnaires sent to patients will be presented.

PMID- 18637441
TI  - [Endoscopic surgery for selected tumors of the nose and paranasal sinuses-
      practical sense of the four hands technique].
AB  - Endoscopic sinus surgery is a gold standard in chronic sinusitis since middle
      '80. More and more attention is put on endosnasal tumor removal with the
      endoscopic technique. Two major pathologies are present in the literature, the
      inverted papilloma and the angiofibroma. Other tumors are rare. In the ENT
      Department of Poznan Medical University, endoscopic removal of tumors of the nose
      and paranasal sinuses is done with the four hands technique. Since November 2006
      to July 2007 12 cases were operated in our institution. Fully endoscopic removal
      was performed in 7 cases. In 2 cases an endoscopic assisted surgery was
      performed. In 3 cases a convertion to open surgery was necessary. Endoscopic
      approach to nonmalignant tumor of the nose and parana sal sinuses is an
      alternative to open surgery of tumor of the nose and paranasal sinuses. The four
      hands technique is very helpful and leads to extend limits of this surgery.
      Performing an endoscopic surgery of tumor one has to be prepared to make an
      intraoperative convertion to open surgery.

PMID- 18637442
TI  - [Prognostic molecular markers in oral and lip squamous cell carcinoma--evaluation
      of expression and its significance].
AB  - INTRODUCTION: Head and neck cancer treatment optimization and individualization
      has become possible due to the implementation of the prognostic and predictive
      molecular markers in diagnostics. AIM: The aim of this study was an attempt to
      determine which of the investigated molecular markers may have prognostic and
      predictive value in head and neck cancers. MATERIALS AND METHODS: The paraffin
      blocks from 47 patients with oral and lip squamous cell carcinoma (SCC) after
      surgical treatment in the Institute of Oncology in Gliwice in the period of 1998
      2002 were investigated. For immunohistochemical studies the DAKO monoclonal
      antibodies were used: p53, Ki67, Cyclin D1, Cathepsin B and Cox2-Cayman Chemical
      antibody. Staining reactions were evaluated at 400x magnification. The average
      percent of staining cells was estimated in every case in the groups of patients
      with (N+) and without (No) node metastases. The results were subsequently
      juxtaposed with selected clinical and histological parameters. Statistical
      analysis was performed with Mann-Whitney and Kruskal-Wallis tests and the log
      rank test with a significance level of 0.05 (p = 0,05). RESULTS: Significantly
      higher expression of Ki67 in N+ patients (p = 0,010) were recorded, although
      average staining in the group of treated and the group of unhealed patients was
      statistically insignificant. Cathepsin B expression (<20% and > 20%) was
      correlated with 3 year-long survival and a slight higher average staining (33,5%)
      in unhealed in comparison with treated patients (29,0%) was notified. Everage
      expression of p53 in unhealed patients (33,1%) was slightly higher than in
      treated ones (28,4%). Weaker Cyclin D1 expression (<10%) correlated with higher
      disease free survival. Average Cycline D1 staining in the groups of unhealed
      patients (19,6%) was higher than in the treated ones (12,0%). There were no
      significant differences in COX-2 staining in correlation with clinical and
      histological parameters. CONCLUSIONS: Lower expression of Cyclin D1 and Cathepsin
      B in neoplastic cells correlated with higher percentage of disease free survival
      what suggests the prognostic value of these markers. Higher proliferation
      activity of primary tumor neoplastic cells correlated with node metastases what
      may has the predictive value in the course of the disease.The different markers
      expressions observed in the different oral cavity localizations confirm the
      necessity to select patients for further investigations with respect to uniform
      disease changes topography.

PMID- 18637443
TI  - [Hearing organ function in children with nephrotic syndrome in the course of
      primary glomerulopathy].
AB  - Nephrotic syndrome (NS) is connected with an increase of glomeral permeability.
      It generates numerous, reversible electrolic and biochemical disturbances. THE
      AIM of the work was complex evaluation of hearing organ in children in the course
      of NS. MATERIAL: 28 children aged from 7 to 17 years suffering from primary
      glomerulopathy, without renal failure and 28 healthy children in the relative age
      (control group). METHOD: In children with NS hearing tests (pure tone audiometry,
      impedance audiometry, BAEP, DPOAE) have been performed twice: in acute phase and
      in non-symptomic phase. Such parameters as total protein, albumines, globulins,
      cholesterol, sodium, potassium, calcium, magnesium were evaluated. RESULTS: In
      oedematous stage the concentration of total protein, albumines and calcium were
      significantly decreased and the concentration of cholesterol was increased.
      Children with NS presented much worse hearing than healthy subjects, even after
      the symptoms dissapeared in acute phase such parameters of BAEP as peak III
      latency and interpeak I-III interlatency were elongated and DPOAE values were
      decreased. In normal phase BAEP parameters were similar to those in normal group
      but DPOAE parameters were still much worse than in healthy children. Some of the
      biochemical parameters correlated with hearing results in children with NS.
      CONCLUSIONS: Hearing organ in children with NS in the course of chronic
      glomerulopathy is significantly worse than in healthy children. It is probably
      connected with repeated biochemical and electrolytic disturbances that cause
      partly reversible alterations in the cochlea, acoustic nerve and brain stem. It
      may be also caused by ototoxic drugs.

PMID- 18637444
TI  - [A rare case of plasmocytoma of uvulae and carcinoma of larynx].
AB  - Plasmocytoma solitare is a rare disease of lymphoprolipherative origin. It is
      usually diagnosed occasionally on ORL departaments because of its close relation
      to head and neck localisation. Surgical treatment and/or radiotherapy is a
      treatment of choice. It becomes disseminated after years usually. Carcinoma of
      larynx is a squamos cell carcinoma of well known ethiology strongly corralated
      with alcohol and nicotin abuse. There is described a case of patient in this
      paper, who in a short time of few months developed two neoplasms of different
      histological origin, but localised in the same region of head and neck:
      Plasmocytoma solitary of uvulae and carcinoma of larynx. Due to early diagnoses
      the radical treatment (combined surgery and radiotherapy) was performed. However
      the extremly short time of follow up do not allow to make the observation of the
      DFS and OS of the patient.

PMID- 18637445
TI  - [A rare case of schwannoma of the tongue].
AB  - Author described a rare case of lingual Schwannoma in 20 years old female. After
      complete surgical excision she has not shown recurrence during 2 years of follow
      up. Schwannomas are peripheral nerve tumors of nerve sheath origin. Extracranial
      schwannoma in the head and neck region comprise 25-45% of all shwannomas, but
      only 1% are located intraoral and usually present as slow growing mass of long
      duration, producing few symptoms. The treatment is surgical excision.

PMID- 18637446
TI  - [A case of giant pleomorphic adenoma of the parotid gland].
AB  - INTRODUCTION: A case of pleomorphic adenoma of the parotid gland was reported.
      Pleomorphic adenoma is the most common benign tumor of the major salivary glands.
      A review of the literature confirms that this kind of tumor is less common in the
      minor salivary glands. We described statistic population, types of the
      diagnostic, treatment and clinical course of pleomorphic adenoma of the parotid
      gland. MATERIAL AND METHOD: We encountered such a tumor in a 55-year-old woman
      who was admitted to our Hospital. The only symptom was significant face
      deformation, growing for 30 years. RESULTS: The tumor was located under the right
      side of the face and was removed surgically. No complications were observed in
      the postoperative course but paresis of the facial nerve occurred. The patient
      was discharged from the hospital with the recommendation of facial muscles
      rehabilitation. After the two months from the surgery, paresis was diminished.
      Afterwards contact with the patient got lost. CONCLUSION: Pleomorphic adenoma is
      the most common benign tumor of the major salivary glands. Surgery is the main
      method of the treatment. The most common complication is paresis of the facial
      nerve.

PMID- 18637447
TI  - [Spontaneous temporal bone meningo-encephalocele].
AB  - INTRODUCTION: Spontaneous meningocele or meningoencephalocele of the temporal
      bone are very rare. Mostly they are result from otologic surgery or head trauma.
      Spontaneous meningoencephalocele may occur mostly in the epitympanum or mastoid
      antrum. It could be a result of pathologic obesity. Often it could be
      misdiagnosed because of less symptomatic. The most expected symptoms could be:
      unilateral conductive hearing loss with meddle ear effusion, pulsatile tinnitus
      or CSF leak. MATERIAL AND METHODS: We present a case of 61 year old, obese woman
      with spontaneous meningoencephalocele of the left temporal bone. The patient
      presented symptoms of conductive hearing loss with fullness in the left ear and
      pulsatile tinnitus. The imagine study such as CT scan and MRI showed a dehiscent
      areas in the tegmen at the right side and meningoencephalocele protruding into
      the left mastoid cavity on the left side. RESULTS: After complete diagnosis we
      preformed surgery. A mastoidectomy of the left temporal bone was done and the
      meningoencephalocele tissue was encountered. The bony defect and CSF leak was
      closure. The patient was released from pulsatile tinnitus and fullness in the
      ear, but a component of hearing dysfunction is still present. CONCLUSIONS:
      Spontaneous meningoencephalocele of the temporal bone may occur in an obese
      patient. The most finding will be a middle ear effusion and conductive hearing
      loss with pulsatile tinnitus. The combination of CT and MRI will help in proper
      preoperative diagnosis. The operation include transmastoid, middle cranial fossa
      repair or combination of both. The multi layer closure of bony defect is very
      important to avid CSF leak.

PMID- 18637448
TI  - [Coexistence of acoustic neuroma and pineal region tumor in patient with sudden
      deafness].
AB  - INTRODUCTION: Acoustic neuroma usually presents as an unilateral tumor, seldom -
      bilateral and rarely in coexistence with other central nervous system neoplasms.
      The following paper reports such a case of a 21-year-old male patient presented
      with sudden deafness in left ear accompanied with tinnitus and vertigo. Symptoms
      started 4 weeks prior hospitalization. Their aggravation has been observed 7 days
      before admission to the hospital. Audiometry revealed moderate sensorineural
      hearing loss in left ear (for low and middle frequencies), brainstem auditory
      evoked potentials were absent on the left side and ENG examination showed left
      peripheral vestibular impairment. Initially patient received i.v. vasodilatators
      showing 20-25 dB improvement in low frequencies after 3 days of treatment. MRI
      study revealed in the left internal acoustic meatus mass (7 x 7 x 14 mm)
      suggesting acoustic neuroma and an oval mass (7 x 9 x 14 mm) in the pineal gland
      presenting radiological features of pinealoma. Patient has been qualified for
      neurosurgical treatment. Acoustic neuroma has been removed by suboccipital
      approach and pinealoma has been left for further observation as it was found
      incidentally. Histopathological examination confirmed diagnosis of left VIII
      nerve schwannoma. The left facial palsy (House-Brackmann III/IV grade) and
      profound hearing loss appeared after surgery. The postoperative course shows no
      evidence of acoustic neuroma recurrence.

PMID- 18637449
TI  - [An unusual location of a foreign body in the posterior hypopharynx--case
      report].
AB  - The foreign bodies ingestion are common among the patients admitting to the ENT
      Emergency Unit. Usually the treatment does not cause too much trouble, however,
      the symptoms and possible complications might be potentially life threatening.
      The 64 years old female suffering from severe pain in the hypopharynx and
      dysphagia was introduced to the ENT Emergency Unit of the F. Raszeja City
      Hospital in Poznan. The laryngological examination showed the piece of the needle
      protruding from the back wall of the hypopharynx. The CT scans indicated the tip
      of the needle, touching the transverse processes of the C3 and C4 vertebrae.
      Unfortunately the analysis of the CT scans could not clearly exclude the injury
      of the vertebral artery.

PMID- 18637450
TI  - [Case of paraganglioma of the originally numerous location in the 24 year old
      male].
AB  - INTRODUCTION: Paragangliomas, in other words chemodectomas were bening tumors
      arising from the paragangliomas cells of the parasympathetic system. There are
      four kinds of paragangliomas: carotic artery baroreceptors (glomus caroticum),
      tympanic cavity (glomus tympanicum), internal jugular vein (glomus jugulare) and
      placed along vagal nerve (glomus vagale). Overall 5-10% of all paragangliomas are
      malignant. The bening lorms paragangliomas, of the originally numerous location
      are rare described. MATERIAL AND METHODS: The authors describe the rare case of
      24 yrs old male, of the bening form paraganglioma of the originally numerous
      location - glomus tympanicum on the left site, glomus caroticum on the right
      site. RESULTS: The patient was successfuly treated surgicaly. CONCLUSIONS: The
      first choice of treatment is surgery. The diagnosis of a suspected paraganglioma
      can be confirmed with USG, CT, Angio CT, Angiography and MRI. Radiation therapy
      may be usefull in those cases in which the residual tumor was known to be left.

PMID- 18637451
TI  - [Julian Kosinski (1833-1914)--especially meritous surgeon for the development of
      otorynolaryngology. His achievements in therapy of diseases of larynx].
AB  - The achievements in surgical treatment of larynx diseases by Julian Kosinski
      (1833-1914), an eminent Warsaw surgeon, the head of Surgical Clinic in Main
      School and Warsaw Imperial University performed according to contemporary world
      wide standards are presented in more detail. His successful surgical treatment
      such diseases as postinflammatory adhesions of larynx, diphtheria, syphilis of
      larynx, polyps of larynx and other are described in some more detail. The
      laryngectomy by Theodor Billroth in 1873 are described in short. The analysis the
      first laryngectomy in Polish territories performed by Julian Kosinski ("the tenth
      world laryngectomist") in 1877 is performed with full particulars. The surgical
      difficulties, the postoperating management are discussed. The reasons of failures
      of the laryngectomies in XIX century are analysed widely.

PMID- 18637452
TI  - [Julian Kosinski (1833-1914)--especially meritorious surgeon for the development
      of otorhinolaryngology. His achievements in therapy of ear, nose, throat and
      borderland diseases].
AB  - The professional and scientific activities of Julian Kosinski (1833-1914), an
      eminent Varsovian surgeon, his thorough medical education in various European
      countries is shortly outlined. He was the versatile surgeon, the head of Surgical
      Clinic in the Main School and in the Imperial Warsaw University. Kosinski was the
      creator of "Varsovian surgical school". Kosinski's successful surgical treatment
      of otorhinopharyngeal diseases and the borderland (such as auricle's fibroma,
      keloid and periauricular atheroma, carcinomas of nasi and other parts of face,
      sarcomas of nasopharyngeal cavity and pharynx and maxillary sinus, syphilis of
      face, tuberculous ulceration of tongue, osteomas of palate and pharynx, foreign
      bodies of oesophagus, inflammations of parotid gland and other) are described in
      some more detail. The surgical therapy in that region such as plastic
      reconstruction of face, oesophagotomy was performed according to contemporary
      world-wide standards.

PMID- 18637453
TI  - [Equilibrium disorders in patients with multiple sclerosis].

PMID- 18637454
TI  - [Report from the Fourth International Conference: A sound foundation through
      early amplification--Chicago 6-8 .12.2007].

PMID- 18637455
TI  - An analysis of long-term survival from the OPTN/UNOS Pancreas Transplant
      Registry.
AB  - Based upon data reported to the OPTN/ UNOS Pancreas Transplant Registry from
      October 1987- November 2007, overall deceased donor pancreas graft survival rates
      at 10 years improved from 43% for transplants prior to 1990 to 48% for
      transplants between 1995-1999. Overall graft survival rates have not improved
      substantially since 2000. The major causes of pancreas graft failure were
      technical (40%) and acute rejection (15%) during the early posttransplant period,
      and chronic rejection (25%) of grafts that survived more than 6 months. Pancreas
      graft survival rates were better for recipients of SPK grafts (83%, 69%, 51% and
      33% at one, 5 10 and 15 years, respectively) than for PTA recipients (74%, 45%,
      24% and 13% at the same intervals) or PAK recipients (78%, 54%, 28% and 9% at
      one, 5, 10 and 15 years, respectively).

PMID- 18637456
TI  - HLA mismatches and PRA in kidney retransplants.
AB  - 1. For kidney transplants, overall graft survival with 1st transplants was better
      than with multiple transplants. 2. One-year graft survival rates have become
      similar with 1st and 2nd transplants, but some differences persisted for 5-year
      survival. 3. HLA mismatches have decreased with both 1st and 2nd DDTs, but with
      1st and 2nd LDTs HLA mismatches remained at almost the same level. 4. PRA levels
      increased with the number of transplants. 5. The percent of 1st transplant
      patients with 0% PRA has increased year by year. However, with 2nd transplants
      the percent with higher PRA levels also increased year by year. 6. The trend in
      number of HLA mismatches was similar with both 1st and 2nd DDTs and LDTs even
      when higher HLA mismatch levels increased over the years. 7. The graft survival
      of all PRA levels improved. The differences in 1-year graft survival between each
      PRA group became smaller, and pretransplant PRA diminished with 1-year graft
      survival. However, pretransplant PRA still affected 5-year graft survival.

PMID- 18637457
TI  - Steroid-free immunosuppression in kidney transplant recipients: the University of
      Minnesota experience.
AB  - As results after transplants continue to improve, the burden associated with long
      term immunosuppression and the complications associated with these agents become
      more significant. Recent trends in immunosuppression minimization strategies show
      that prednisone minimization protocols are not associated with significantly
      increased acute rejection or chronic graft dysfunction. With long-term data now
      available, we can see that the majority of such recipients (>80%) can remain
      prednisone free. There seems to be no compromise in terms of long-term results,
      and a definite improvement with regard to steroid-related and viral
      complications. These protocols can be used in minorities, children, and higher
      immunologic risk kidney transplant recipients, and in liver and pancreas
      recipients. The question of what is the ideal maintenance agent to couple with
      prednisone-free regimes remains unclear, and it may be that different agents may
      be better suited for different groups of recipients. Why is prednisone
      minimization now possible, when previous attempts were unsuccessful? Several
      explanations are possible. Early attempts concentrated on steroid withdrawal -
      removing prednisone once the patient had been on therapy for at least 3 months
      (18-20). Outcomes differ between studies reporting rapid prednisone withdrawal
      and those reporting prednisone withdrawal at a later time, but it is not clear
      why rapid prednisone withdrawal has succeeded and late prednisone withdrawal has
      failed. Other factors may include the routine use of polyclonal antibody for
      induction therapy and the use of newer immunosuppression agents such as MMF, TAC,
      and SRL. Finally, the newer trials of prednisone minimization have been performed
      in a different era, a time when results have improved as has our understanding of
      the risk factors associated with long-term graft survival. While ongoing follow
      up of this group of patients will continue to be important, our experience
      suggests that maintenance prednisone is likely not required for the majority of
      kidney transplant recipients today.

PMID- 18637458
TI  - Corticosteroid elimination: the Cincinnati experience.
AB  - Elimination of corticosteroid-related morbidity has been a goal of transplant
      clinicians from the earliest days of renal transplantation more than 50 years
      ago. Over the past decade, this goal has begun to be realized. Herein, we
      describe our efforts to eliminate corticosteroid therapy from maintenance
      immunosuppression-efforts that have spanned 15 years and have included design and
      conduct of five multicenter trials and over ten single center trials with over
      650 patients at the University of Cincinnati. These efforts have led to a near
      complete elimination of corticosteroid-related morbidity, and, importantly, a
      more precise definition of the risk/benefit assessments of corticosteroid
      withdrawal in individual patient populations, which has allowed individualization
      and tailoring of corticosteroid-free immunosuppression.

PMID- 18637459
TI  - Current challenges in renal transplantation from deceased donors.
AB  - The results of 3,165 kidney transplants from deceased donors during the 3 time
      periods, 1986-92 (n=882), 1993-99 (n=1,107) and 2000-06 (n=1,176) were analysed
      and following conclusions could be made: 1. One-year patient survival improved
      from 93.2% to 98.1%, one-year graft survival improved from 86.1% to 95.1% and one
      year death censored graft survival improved from 90.4% to 96.6%. Patient death
      due to cardiovascular disease decreased significantly. Despite that, patient
      death with a functioning graft became the main cause of graft loss after the
      first posttransplant year in our most recent cohort. The estimated graft half
      life has improved from 9.3 to 20.4 years. 2. The rejection incidence decreased
      from 28.1% to 14.1%. 3. The mean donor age increased from 35.5 to 47.8 years. The
      proportion of donors fulfilling the UNOS criteria for extended criteria donors
      increased from 2.9% to 26.3%. The long-term effects of donor factors on these
      transplants need to be critically evaluated. 4. A good HLA match remains a sound
      basis for kidney allocation. Provisions should be made for highly immunized
      patients and those with unusually long waiting times.

PMID- 18637460
TI  - Present status at the Vienna Transplantation Center after four thousand renal
      transplantations.
AB  - The Division of Transplantation at the Medical University of Vienna, Austria was
      established by Dr Franz Piza, who performed the first deceased donor kidney
      transplantation in Vienna in 1965. During the next 43 years, 4,849 transplants
      were performed at this unit. Data were analysed in the time period 1993-2006 for
      2,165 deceased donor transplants (1,734 first and 431 regrafts) and 263 living
      donor transplants. Long-term follow-up was available for more than 95% of all
      grafts and all recipients had at least 9 months of follow-up. Two- and 6-year
      graft survival rates were 81.4% and 66.3%, respectively, for first deceased donor
      grafts, 76.1% and 61.8% for regrafts and 91.5% and 79.1% for living transplants.
      Appropriate immunosuppression, HLA matching and crossmatching supported by solid
      basic scientific research have proved successful in achieving good graft survival
      at our unit.

PMID- 18637461
TI  - Recent trends in heart transplantation: the University of Vienna experience.
AB  - Since the beginning of the University of Vienna Cardiac Transplant Program in
      1984, 1086 heart transplant procedures have been performed through the end of
      2007. One- and five-year survival has increased steadily over time (82% and 76%).
      Ten-year survival is 65%. Over the past 10 years our program has seen dramatic
      changes in patient selection, accepting now patients with more risk factors (Age,
      diabetes, elevated pulmonary resistance,..). Developments in immunosuppression
      have decreased incidence of infection, rejection and graft arteriosclerosis
      continuously. Our program continues to pursue novel strategies to improve the
      survival and quality of life of our heart transplant patients.

PMID- 18637462
TI  - Lung transplantation at Duke University Medical Center.
AB  - Lung transplantation has undergone remarkable changes in clinical practice to
      address the higher rate of rejection and mortality. Our protocols include
      increased immunosuppression and strategies to address non-alloimmune injury,
      including GER. New and innovative approaches to lung transplantation are still
      needed to improve short- and long-term outcomes. The LAS implementation has had a
      strong influence on the type of native disease transplanted at our center as well
      as our waiting list time. However, the LAS was not predictive of survival
      posttransplant at one year. Further refinements of the LAS and protocols may
      improve survival posttransplant.

PMID- 18637463
TI  - Cleveland Clinic lung transplantation: update 2008.

PMID- 18637464
TI  - Lung transplantation: a 15-year single-center experience.
AB  - During the past decade, the outcome after lung transplantation has improved due
      to a substantial reduction in the immediate postoperative and perioperative
      mortality that resulted from better surgical techniques, anaesthetic and
      perioperative management and more intense antibiotic, antifungal and antiviral
      prophylaxis. However, according to the International Society for Heart and Lung
      transplantation (ISHLT) Registry, the long-term survival has not improved much in
      recent years and mortality is most often due to the development of chronic
      allograft dysfunction, infections, posttransplant lymphoproliferative disorders
      and other tumours. Although treatment options have improved for most of these
      issues, therapy for chronic allograft dysfunction has been very disappointing.
      Recent observations using azithromycin and antireflux surgery may shed more light
      on the pathophysiology and perhaps the outcome of this debilitating condition. We
      hope that better prevention and treatment of chronic allograft dysfunction will
      result in better long-term survival after lung transplantation.

PMID- 18637465
TI  - The Alfred Hospital lung transplant experience.
AB  - There has been considerable evolution in the pre-, peri- and postoperative
      management of patients with severe lung disease undergoing LTx. Compared with
      where we started at the Alfred Hospital in 1990, in 2008 we now recognize that
      the majority of donor lungs that are offered for LTx (including DCD lungs) are
      useable, patients with a wide range of ages and disease processes are suitable to
      be considered for LTx and modern surgical, anesthetic and ICU management should
      result in a 90% one-year survival rate. It is likely that the procedural mix in
      LTX servicing will remain little changed in the years to come, with BLTx being
      the pre-eminent service modality for the majority of end-stage lung disease
      patients. SLTx will remain a viable procedure almost exclusively for the IPF
      recipient, with HLTx a necessity for the congenital heart disease patient, for
      whom all other medical and surgical options have been exhausted. Notwithstanding
      theseconsiderable achievements, including the factthat one-third of patients now
      survive more than10 years, it is also apparent that BOS and recurrent infections
      remain a problem limiting the overall success of LTx. Understanding more about
      the interactions between the immunosuppressive regimen, infective agents
      (particularly viruses) and the recipients responses to all of the abovehold the
      keys to improving these late outcomes.

PMID- 18637466
TI  - Adult liver transplantation: the Paul Brousse experience.
AB  - During the past 3 decades, more than 2,250 liver transplants were performed at
      Paul Brousse Hospital. Overall patient survival was 82% at one year, 71% at 5
      years and 64% at 10 years. Our group has developed a variety of approaches to
      liver transplantation, including: 1. Anti HBs immunoglobulin prophylaxis for the
      prevention of HBV recurrence. Combination prophylaxis with lamivudine and anti
      HBs immunoglobulins reduced the rate of HBV re-infection to 20%. 2.
      Transplantation of HIV-HCV and HIV-HBV infected patients. These transplants are
      feasible and we achieved 2- year survival rates of 70% and 90%, respectively. The
      main problem was HCV recurrence which was more severe in HIV co-infected
      patients. 3. Transplantation for hepatocellular carcinoma on a cirrhotic liver
      with a single tumor <5 cm or <3 tumors <3 cm. 4. Transplantation for familial
      amyloidotic polyneuropathy (FAP). The 5- and 10-year survival rates were 76% and
      72%, respectively. More than 100 livers obtained after hepatectomy from FAP
      patients were transplanted as "domino" living donor livers to patients with
      unresectable liver cancers with a 5-year survival rate of 64%. In some domino
      recipients, symptoms of FAP disease occurred more rapidly than expected and this
      could be an indication for a second transplantation of a non FAP-liver. 5. Split
      liver transplantation for pediatric patients. This has increased the number of
      transplantable livers for children by 28%. 6. Split-liver transplantation for 2
      adults. The grafts were prepared by ex-vivo or in-situ splitting and the overall
      5-year survival rate was 56%. 7. Adult -to-adult living-related liver
      transplantation. There has been no mortality nor late complications in donors and
      the overall 5-year survival rate among recipients was 73%. 8. Liver
      retransplantation with good results in the elective situation. Retransplantation
      should be used with discretion in the emergency setting.

PMID- 18637467
TI  - Liver transplantation at the Miami Transplant Institute: a 14-year single-center
      experience.
AB  - The clinical outcome of LT has improved significantly with refinements in
      surgical skill and immunosuppressive agents. Over the past decade, nationally
      most LT centers have improved their standard care in LT. As a result, short-term
      survival after LT has increased remarkably. However, recurrence of original liver
      disease, chronic rejection, and the adverse effect of immunosuppressive agents
      still impose significant limitations on long-term survival. Here at the MTI, it
      is our mission to continue technical innovation, improve the management of
      hepatitis C patients, search for better immunosuppressive protocols, and work
      towards achieving tolerance after LT to improve the long-term outcome.

PMID- 18637468
TI  - A quarter century of liver transplantation at UCLA.
AB  - Orthotopic liver transplant (OLT) has become the best and most durable treatment
      for end stage liver disease (ESLD) of any etiology. The UCLA program, established
      in 1984, has accumulated one of the world's most extensive experiences with this
      procedure. The UCLA experience has been built on the classical techniques of
      Starzl, yet has forged innovations such as split liver transplantation and use of
      extended criteria donor organs. The UCLA program also reports one of the largest
      experiences in pediatric liver transplantation and has demonstrated that
      recipient renal function is a main predictor of post-transplant survival. UCLA
      has offered further evidence that criteria for liver transplantation for
      hepatocellular carcinoma (HCC) should be expanded. As the 21st Century
      progresses, the Dumont-UCLA Liver Transplant program will continue its efforts to
      improve outcomes for all patients with endstage liver disease.

PMID- 18637469
TI  - Epitopes of the HLA-A, B, C, DR, DQ and MICA antigens.
AB  - The intent for this chapter was to summarize the HLA epitopes that have been
      defined by adsorption and elution of antibodies from single HLA antigens to date.
      Examples of reactions of mAb and eluted allosera with the class I, class II and
      MICA SA are also presented. We have identified 103 HLA class I epitopes, of which
      40 were defined by mAbs and 63 by alloantibodies mostly eluted from rHLA class I
      single antigen cell lines. We identified 32 epitopes shared by A-locus antigens,
      43 epitopes shared by B-locus antigens, 4 epitopes shared by C-locus antigens, 16
      inter-locus epitopes shared by A-B loci antigens, 5 inter-locus epitopes shared
      by B-C loci antigens and 3 inter-locus epitopes shared by A-B-C-locus antigens.
      Sixty HLA-DR epitopes have been defined, most by one aa residue on the HLA DR
      beta chain. However, as is the case with Class I epitopes, some DR epitopes are
      defined by one or more alternative residue(s). Eighteen HLA-DQ epitopes have been
      identified on the HLA-DQB chain and on the HLA-DQA chain of HLA-DQ antigens. Most
      DQ epitopes were defined by one aa residue. However, almost half are
      characterized by several alternative combinations of aa residues. Only a few DQA
      epitopes have been identified. Seven MICA epitopes have been defined to date. All
      are defined by a single aa residue.

PMID- 18637470
TI  - HLA class II DP epitopes.
AB  - Both alpha (DPA1) and beta (DPB1) peptide chains of class II HLA-DP heterodimers
      contain polymorphic regions. Five DPB1 epitopes, for which we propose numbers
      #4001-4005, were identified by the reaction patterns ofthe DPB1 antibodies to
      DPB1 alleles of DP single antigen beads. Epitopes were defined by unique amino
      acids shared by the positive antigens of theantibodies. The unique amino acids
      for #4001 are DEAV at positions 84-87; for #4002, they are DED at positions 55
      57; for #4003, DEE at positions 55-57; for #4004, Q at position 33; for #4005,
      the unique amino acids may be GGPM at positions 84-87. An antibody to epitope
      #4001-shared by DPB1*01, 03, 05, 09, 10, 11, 13, 14, 17, 19- could be absorbed by
      the cell line of DPB1*01 typing. This eluted antibody was reactive to all the
      DPB1 #4001 specificities. So this test demonstrated that a single antibody was
      reactive to the epitope shared by multiple antigens.

PMID- 18637471
TI  - Prediction of immunogenic epitopes--is it feasible?

PMID- 18637472
TI  - Allosensitization to HLA and MICA is an important measure of renal graft outcome.
AB  - The objective of this study was to evaluate the donor-specific antibody
      repertoire against T and B cells and monocytes, as well as the non-donor anti
      HLA, and MICA (MHC class I-related chain A) antibodies in recipients of the live
      related donor renal transplantation. Sera collected before and after
      transplantation were tested by ELISA for the presence of HLA class I- and class
      II-specific antibodies and by Luminex MICA single-antigen bead assay for the
      detection of MICA antibodies. Patients having a combination of both anti-HLA and
      MICA antibodies had worse graft survival and more rejection episodes as compared
      to the group without antibodies. Further, presence of IgG antibodies against the
      donor cells (T, B & monocytes) led to a compromised graft survival along with
      higher incidence of acute rejection as compared to the negative groups. These
      results suggest that a comprehensive assessment of anti-donor antibody repertoire
      and monitoring of anti-HLA, MICA antibodies following transplantation is a useful
      exercise to detect the sensitization status of the recipient and this can prove
      to be of immense prognostic value in renal transplantation.

PMID- 18637473
TI  - Increased lung allograft failure in patients with HLA-specific antibody.
AB  - In this prospective study we report on a higher prevalence of lung allograft
      failure in patients with HLA-specific alloantibody, at two and four years of
      follow-up. Our report follows an increasing number of previous studies which have
      shown that anti-HLA alloantibody is a major risk factor for worse outcome in lung
      transplantation. Anti-class I and II HLA antibodies are reported to cause
      hyperacute rejection in lung allograft which can largely be avoided by a thorough
      analysis of sensitized candidates. Pre-transplant screening by multiple methods,
      including solid-phase/ single-antigen assays, can improve the sensitivity and
      specificity of virtual crossmatches and can identify additional acceptable
      mismatches resulting in an increased transplantability rate of highly sensitized
      candidates. Furthermore, posttransplant anti-HLA antibodies were strongly
      associated with a worse lung allograft outcome. Recipients that exhibited humoral
      allosensitization experienced an increased frequency of refractory acute
      rejection. The prevalence of lymphocytic bronchiolitis and decreased pulmonary
      function was also higher in antibody producers when compared to patients without
      anti-HLA antibody. The presence of specific C4d deposition in lung capillaries,
      as well as increased soluble C4d in bronchoalveolar lavage fluid, are markers of
      antibody-mediated rejection and are found especially in patients with mixed forms
      of rejection. Chronic lung allograft dysfunction, diagnosed as bronchiolitis
      obliterans syndrome, was higher in patients with anti-HLA antibody and was
      preceded by circulating antibody. The improved detection and characterization of
      anti-HLA antibody and the availability of additional therapeutic strategies to
      target the humoral alloimmune response should improve the clinical management of
      lung transplant recipients.

PMID- 18637474
TI  - The co$t of mi$matching.
AB  - We have shown that the number of HLA mismatched antigens correlates with the
      development of new or changes in existing HLA-specific antibodies. We have
      further shown that the magnitude of the effect varies among groups defined by
      whether or not HLA-specific antibody was present prior to transplant, by the
      transplant number, by recipient race, and by donor type. The increases in
      antibody, which increase with increasing degree of mismatch, result in
      differences in waiting times reflective of the number of previous mismatches. For
      many patients, increased waiting time represents not only reduced quality of life
      but deteriorating health and shortened life expectancy. Globally, increased
      waiting times translate into increased costs for dialysis, antibody testing, and
      health care. These factors suggest that HLA matching should not be abandoned but
      should be given consideration for those patients most affected by mismatches.

PMID- 18637475
TI  - The history of the University of Wisconsin transplant program.

PMID- 18637476
TI  - The origins of collaborative organ salvaging and sharing: Los Angeles, 1967.

PMID- 18637478
TI  - Worldwide transplant center directory.

PMID- 18637477
TI  - Major transplant centers in the United States.

PMID- 18637479
TI  - Worldwide organ procurement organization directory.

PMID- 18637480
TI  - Innovative endocrinology of cancer. Preface.

PMID- 18637481
TI  - Mechanisms of hormone carcinogenesis: evolution of views, role of mitochondria.
AB  - CumuIative and excessive exposure to estrogens is associated with increased
      breast cancer risk. The traditional mechanism explaining this association is that
      estrogens affect the rate of cell division and apoptosis and thus manifest their
      effect on the risk of breast cancer by affecting the growth of breast epithelial
      tissues. Highly proliferative cells are susceptible to genetic errors during DNA
      replication. The action of estrogen metabolites offers a complementary genotoxic
      pathway mediated by the generation of reactive estrogen quinone metabolites that
      can form adducts with DNA and generate reactive oxygen species through redox
      cycling. In this chapter, we discussed a novel mitochondrial pathway mediated by
      estrogens and their cognate estrogen receptors (ERs) and its potential
      implications in estrogen-dependent carcinogenesis. Several lines of evidence are
      presented to show: (1) mitochondrial localization of ERs in human breast cancer
      cells and other cell types; (2) a functional role for the mitochondrial ERs in
      regulation of the mitochondrial respiratory chain (MRC) proteins and (3)
      potential implications of the mitochondrial ER-mediated pathway in stimulation of
      cell proliferation, inhibition of apoptosis and oxidative damage to mitochondrial
      DNA. The possible involvement of estrogens and ERs in deregulation of
      mitochondrial bioenergetics, an important hallmark of cancer cells, is also
      described. An evolutionary view is presented to suggest that persistent
      stimulation by estrogens through ER signaling pathways of MRC proteins and energy
      metabolic pathways leads to the alterations in mitochondrial bioenergetics and
      contributes to the development of estrogen-related cancers.

PMID- 18637483
TI  - Role of endocrine-genotoxic switchings in cancer and other human diseases: basic
      triad.
AB  - Cancer is one of the leading causes of human death and belongs to the group of
      main chronic noncommunicable diseases (NCD). Certain specific features ofNCD have
      raised the concept of 'normal' and 'successful' aging. The apparent paradox of
      simultaneous increase with aging of the diseases connected with estrogen
      deficiency as well as with estrogenic excess can be explained by the existence of
      the phenomenon of the switching of estrogen effects. An isolated or combined with
      the weakening of hormonal effect increase in genotoxic action of estrogens can
      modify the course ofage-associated pathology. In particular, such changes in
      estrogen effect may alter the biology of tumors to make them less favorable/more
      aggressive. Two other endocrine-genotoxic switchings (EGS) involving phenomena
      ofJanus (dual) function of glucose and adipogenotoxicosis may produce similar
      influences on tumor and other NCD biology. These three phenomena form a'basic
      triad' and can act independently of each other or in concert. EGS and their
      inductors may serve as targets for prevention and, probably, treatment of main
      noncommunicable diseases. The measures to correct components of the 'triad' can
      be divided into several groups aimed to optimally orchestrate the balance between
      endocrine and DNA-damagingeffects of estrogens, glucose and adipose tissue
      related factors.

PMID- 18637484
TI  - Breast development, hormones and cancer.
AB  - Breast cancer originates in undifferentiated terminal structures of the mammary
      gland. The terminal ducts of the Lob 1 of the human female breast, which are the
      sites of origin of ductal carcinomas, are at their peak of cell replication
      during early adulthood, a period during which the breast is more susceptible to
      carcinogenesis. The susceptibility of Lob 1 to undergo neoplastic transformation
      has been confirmed by in vitro studies, which have shown that this structure has
      the highest proliferative activity, estrogen receptor content and rate of
      carcinogen binding to the DNA. The higher incidence of breast cancer observed in
      nulliparous women supports this concept, whereas the protection afforded by early
      full-term pregnancy in women could be explained by the higher degree of
      differentiation of the mammary gland at the time in which an etiologic agent or
      agents act.

PMID- 18637482
TI  - Adaptation to estradiol deprivation causes up-regulation of growth factor
      pathways and hypersensitivity to estradiol in breast cancer cells.
AB  - Deprivation of estrogen causes breast tumors in women to adapt and develop
      enhanced sensitivity to this steroid. Accordingly, women relapsing after
      treatment with oophorectomy, which substantially lowers estradiol for a prolonged
      period, respond secondarily to aromatase inhibitors with tumor regression. We
      have utilized in vitro and in vivo model systems to examine the biologic
      processes whereby Long Term Estradiol Deprivation (LTED) causes cells to adapt
      and develop hypersensitivity to estradiol. Several mechanisms are associated with
      this response including up-regulation of ERalpha and the MAP kinase, PI-3-kinase
      and mTOR growth factor pathways. ERalpha is 4-10 fold up-regulated as a result of
      demethylation of its C promoter, This nuclear receptor then co-opts a classical
      growth factor pathway using SHC, Grb-2 and Sos. This induces rapid nongenomic
      effects which are enhanced in LTED cells. The molecules involved in the
      nongenomic signaling process have been identified. Estradiol binds to cell
      membrane-associated ERalpha which physically associates with the adaptor protein
      SHC and induces its phosphorylation. In turn, SHC binds Grb-2 and Sos which
      results in the rapid activation of MAP kinase. These nongenomic effects
      ofestradiol produce biologic effects as evidenced by Elk-1 activation and by
      morphologic changes in cell membranes. Additional effects include activation of
      the PI-3-kinase and mTOR pathways through estradiol-induced binding of ERalpha to
      the IGF-1 and EGF receptors. A major question is how ERalpha locates in the
      plasma membrane since it does not contain an inherent membrane localization
      signal. We have provided evidence that the IGF-1 receptor serves as an anchor for
      ERalpha in the plasma membrane. Estradiol causes phosphorylation of the adaptor
      protein, SHC and the IGF-1 receptor itself. SHC, after binding to ERalpha, serves
      as the "glue" which tethers ERalpha to SHC binding sites on the activated IFG-1
      receptors. Use of siRNA methodology to knock down SHC allows the conclusion that
      SHC is needed for ERalpha to localize in the plasma membrane. In order to
      abrogate growth factor induced hypersensitivity, we have utilized a drug,
      farnesylthiosalicylic acid, which blocks the binding of GTP-Ras to its membrane
      acceptor protein, galectin 1 and reduces the activation of MAP kinase. We have
      shown that this drug is a potent inhibitor of mTOR and this provides the major
      means for inhibition of cell proliferation. The concept of "adaptive
      hypersensitivity" and the mechanisms responsible for this phenomenon have
      important clinical implications. The efficacy ofaromatase inhibitors in patients
      relapsing on tamoxifen could be explained by this mechanism and inhibitors of
      growth factor pathways should reverse the hypersensitivity phenomenon and result
      in prolongation of the efficacy of hormonal therapy for breast cancer.

PMID- 18637485
TI  - Epidemiology of hormone-associated cancers as a reflection of age.
AB  - In this chapter we review the epidemiology of hormone-associated cancers
      (prostate, breast, endometrial, ovarian, pancreatic and thyroid) paying special
      attention to the variability in the age patterns of cancer incidence rate over
      populations and time periods. We emphasize the comparative analysis of the age
      specific incidence rate curves as a valuable source of hypotheses about factors
      influencing cancer risks in populations in addition to the analysis of the age
      adjusted rates.

PMID- 18637486
TI  - Obesity and diabetes epidemics: cancer repercussions.
AB  - The prevalence of overweight (body mass index, BMI, between 25 and 30 kg/m2) and
      obesity (BMI of 30 kg/m2 or higher) is increasing rapidly worldwide, especially
      in developing countries and countries undergoing economic transition to a market
      economy. One consequence of obesity is an increased risk of developing type II
      diabetes. Overall, there is considerable evidence that overweight and obesity are
      associated with risk for some of the most common cancers. There is convincing
      evidence of a positive association between overweight/obesity and risk for
      adenocarcinoma of the oesophagus and the gastric cardia, colorectal cancer,
      postmenopausal breast cancer, endometrial cancer and kidney cancer (renal-cell).
      Premenopausal breast cancer seems to be inversely related to obesity. For all
      other cancer sites the evidence of an association between overweight/obesity and
      cancer is inadequate, although there are studies suggesting an increased risk of
      cancers of the liver, gallbladder, pancreas, thyroid gland and in lymphoid and
      haematopoietic tissue. Far less is known about the association between diabetes
      mellitus type I (also called insulin dependent diabetes mellitus or juvenile
      diabetes), type II diabetes (called non-insulin dependent diabetes mellitus or
      adult onset diabetes mellitus) and cancer risk. The most common type of diabetes
      mellitus, type II, seems to be associated with liver and pancreas cancer and
      probably with colorectal cancer. Some studies suggest an association with
      endometrial and postmenopausal breast cancer. Studies reporting on the
      association between type I diabetes mellitus, which is relatively rare in most
      populations and cancer risk are scanty, but suggest a possible association with
      endometrial cancer. Overweight and obesity, as well as type II diabetes mellitus
      are largely preventable through changes in lifestyle. The fundamental causes of
      the obesity epidemic-and consequently the diabetes type II epidemic-are societal,
      resulting from an environment that promotes sedentary lifestyles and over
      consumption of energy. The health consequences and economic costs of the
      overweight, obesity and type II diabetes epidemics are enormous. Avoiding
      overweight and obesity, as well as preventing type II diabetes mellitus, is an
      important purpose to prevent cancer and other diseases. Prevention of obesity and
      type II diabetes should begin early in life and be based on the life-long health
      eating and physical activity patterns. Substantial public investments in
      preventing overweight, obesity and type II diabetes mellitus are both appropriate
      and necessary in order to have a major impact on their adverse health effects
      including cancer.

PMID- 18637487
TI  - Progesterone receptor action: translating studies in breast cancer models to
      clinical insights.
AB  - Progesterone receptors (PR) are useful prognostic indicators of breast cancers
      likely to respond to anti-estrogen receptor (ER) therapies. However, the role of
      progesterone, therapeutic progestins, or unliganded or liganded PRin breast
      cancer development or progression remains controversial. PR are ligand-activated
      transcription factors that act in concert with intracellular signaling pathways
      as "sensors" of multiple growth factor inputs to hormonally regulated tissues,
      such as the breast. The recently defined induction of rapid signaling events upon
      progestin-binding to PR-B provides a means to ensure that receptors and
      coregulators are appropriately phosphorylated as part of optimal transcription
      complexes. PR-activated kinase cascades may provide additional avenues for
      progestin-regulated gene expression independent of PR nuclear action. Herein, we
      present an overview ofprogesterone/PR and signaling cross-talk in breast cancer
      models and discuss the potential significance ofprogestin/PR action in breast
      cancer biology using examples from both in vitro and in vivo models, as well as
      limited clinical data. Kinases are emerging as key mediators of PR action. Cross
      talk between PR and membrane-initiated signaling events suggests a mechanism for
      coordinated regulation ofgene subsets by mitogenic stimuli in hormonally
      responsive normal tissues. Dysregulation of this cross-talk mechanism may
      contribute to breast cancer biology; further studies are needed to address the
      potential for targeting PR in addition to ER and selected protein kinases as part
      of more effective breast cancer therapies.

PMID- 18637488
TI  - Aromatase expression in women's cancers.
AB  - Estrogen has been positively linked to the pathogenesis and growth of three
      common women's cancers (breast, endometrium and ovary). A single gene encodes the
      key enzyme for estrogen biosynthesis named aromatase, inhibition of which
      effectively eliminates estrogen production in the entire body. Aromatase
      inhibitors successfully treat breast cancer, whereas their roles in endometrial
      and ovarian cancers are less dear. Ovary, testis, adipose tissue, skin,
      hypothalamus and placenta express aromatase normally, whereas breast, endometrial
      and ovarian cancers overexpress aromatase and produce local estrogen exerting
      paracrine and intracrine effects. Tissue specific promoters distributed over a 93
      kilobase regulatory region upstream of a common coding region alternatively
      control aromatase expression. A distinct set of transcription factors regulates
      each promoter in a signaling pathway- and tissue-specific manner. In cancers
      ofbreast, endometrium and ovary, aromatase expression is primarly regulated by
      increased activity of the proximally located promoter 1.3/II region. Promoters
      I.3 and II lie 215 bp from each other and are coordinately stimulated by PGE2 via
      a cAMP-PKA-dependent pathway. In breast adipose fibroblasts exposed to PGE2
      secreted by malignant epithelial cells, activation of PKC potentiates cAMP-PKA
      dependent induction ofaromatase. Thus, inflammatory substances such as PGE2 may
      play important roles in inducing local production of estrogen that promotes tumor
      growth.

PMID- 18637489
TI  - Proteomics of cancer of hormone-dependent tissues.
AB  - Serum and tissue biomarkers have begun to play an increasingly important role in
      the detection and management of many cancers of hormone-sensitive tissues.
      Specifically, the introduction of serum PSA measurements into clinical practice
      has dramatically altered detection and treatment of prostate cancer and serum
      tumor markers play a critical role in the management of testicular cancer. Serum
      biomarkers are used for ovarian and pancreatic cancers, but their usefulness is
      limited by poor specificity. Tissue biomarkers are used to help guide breast
      cancer treatment but are not widely used in other cancers. Even the "best"
      biomarkers such as PSA have substantial limitations. The discovery of new
      biomarkers for both early detection and prognosis of cancer is critical to the
      hope of better clinical outcomes. Recently there has been an expanding
      understanding of the underlying molecular etiology of cancer and molecular
      targeted therapies for some particularly aggressive cancers such as renal cell
      carcinoma have been developed. Better understanding of the molecular etiology of
      cancer and identification of additional therapeutic targets remain important
      research goals. Currently, there are very few patient-tailored therapies and
      there is a great need to better understand the molecular alterations associated
      with cancer and to use this information to design need cancer therapies and
      prevention strategies. Advances in proteomic technologies have created tremendous
      opportunities for biomarker discovery and biological studies of cancer. The
      potential that proteomics will impact clinical practice is currently greater than
      ever, but there main several obstacles in making this a reality. A major hurdle
      to overcome continues to be the proper acquisition of patient tissues and body
      fluids for investigation and clinical diagnostics. Each cancer has specific
      issues in this regard and it is incumbent upon investigators and collaborating
      clinicians to understand the various nuances of tissue and biofluid procurement.
      This chapter not only reviews the clinical need and potential impact of proteomic
      studies of hormone-sensitive cancers, but details specific technologies and
      discusses the issues surrounding tissue/biofluid procurement.

PMID- 18637490
TI  - Endogenous hormone levels and risk of breast, endometrial and ovarian cancers:
      prospective studies.
AB  - Multiple lines of evidence support a central role of hormones in the etiology of
      breast, endometrial and ovarian cancers. Evidence of an association between
      circulating hormones and these cancers varies by both hormone and cancer site,
      with the most consistent associations observed for sex steroid hormones and
      breast cancer risk among postmenopausal women. Recently, evidence has begun to
      accumulate suggesting an important role for endogenous hormones in premenopausal
      breast cancer, endometrial cancer and possibly ovarian cancer. In this chapter,
      prospective epidemiologic studies, where endogenous hormones are measured in
      study subjects prior to disease diagnosis, are summarized. Overall, a strong
      positive association between breast cancer risk and circulating levels of both
      estrogens and testosterone has now been well confirmed among postmenopausal
      women; women with hormone levels in the top 20% of the distribution (versus
      bottom 20%) have a two-to-three-fold higher risk of breast cancer. Evidence
      amongpremenopausal women is more limited, though increased risk associated with
      higher levels of testosterone is consistent. Evidence to date of hormonal
      associations for endometrial cancer is limited, though a strong association with
      sex steroid hormones is suggested. Studies of ovarian cancer have been few and
      small with no consistent associations observed with endogenous hormones. Clearly
      more evaluation is needed to confirm the role of endogenous hormones in
      premenopausal breast cancer, endometrial cancer and ovarian cancer.

PMID- 18637491
TI  - Hormonal heterogeneity of endometrial cancer.
AB  - Endometrial cancer is the most common malignant tumor of the female genital tract
      in the developed world. Increasing evidence suggests that the majority of cases
      can be divided into two different types ofendometrial cancer based on clinico
      pathological and molecular characteristics. Type I is associated with an
      endocrine milieu of estrogen predominance. These tumors are ofendometroid
      histology and develop from endometrial hyperplasia. They have good prognosis and
      are sensitive to endocrine treatment. Type II endometrial cancers are not
      associated with a history of unopposed estrogens and develop from the atrophic
      endometrium of elderly women. Mainly, they are of serous papillary or clear cell
      morphology, have a poor prognosis and do not react to endocrine treatment. Both
      types of endometrial cancer probably differ markedly with regard to the molecular
      mechanisms of transformation. The transition from normal endometrium to a
      malignant tumor is thought to involve a stepwise accumulation of alterations in
      cellular mechanisms leading to dysfunctional cell growth. This chapter reviews
      the current knowledge of the molecular mechanisms commonly associated with
      development of type I and type II endometrial cancer.

PMID- 18637492
TI  - Cell cycle machinery: links with genesis and treatment of breast cancer.
AB  - Loss of normal growth control is a hallmark of cancer. Thus, understanding the
      mechanisms of tissue-specific, normal growth regulation and the changes that
      occur during tumorigenesis may provide insights of both diagnostic and
      therapeutic importance. Control of cell proliferation in the normal mammary gland
      is steroid hormone (estrogen and progestin)-dependent, involves complex
      interactions with other hormones, growth factors and cytokines and ultimately
      converges on activation of three proto-oncogenes (c-Myc, cyclin D1 and cyclin E1)
      that are rate limiting for the G1 to S phase transition during normal cell cycle
      progression. Mammary epithelial cell-specific overexpression of these genes
      induces mammary carcinoma in mice, while cyclin D1 null mice have arrested
      mammary gland development and are resistant to carcinoma induced by the neu/erbB2
      and ras oncogenes. Furthermore, c-Myc, cyclins D1, E1 and E2 are commonly
      overexpressed in primary breast cancer where elevated expression is often
      associated with a more aggressive disease phenotype and an adverse patient
      outcome. This may be due in part to overexpression of these genes conferring
      resistance to endocrine therapies since in vitro studies provide compelling
      evidence that overexpression of c-Myc and to a lesser extent cyclin D1 and cyclin
      E1, attenuate the growth inhibitory effects of SERMS, antiestrogens and
      progestins in breast cancer cells. Thus, abnormal regulation of the expression of
      cell cycle molecules, involved in the steroidal control of cell proliferation in
      the mammary gland, are likely to be directly involved in the development,
      progression and therapeutic responsiveness of breast cancer. Furthermore, a more
      detailed understanding of these pathways may identify new targets for therapeutic
      intervention particularly in endocrine-unresponsive and endocrine-resistant
      disease.

PMID- 18637493
TI  - Selective estrogen modulators as an anticancer tool: mechanisms of efficiency and
      resistance.
AB  - The majority of breast cancers are estrogen receptor (ER) positive and depend on
      estrogen for growth. Therefore, blocking estrogen mediated actions remains the
      strategy of choice for the treatment and prevention of breast cancer. The
      selective estrogen receptor modulators (SERMs) are molecules that block estrogen
      action in breast cancer, but can still potentially maintain the beneficial
      effects of estrogen in other tissues, such as bone and cardiovascular system.
      Tamoxifen, the prototypical drug of this class has been used extensively for the
      past 30 years to treat and prevent breast cancer. The target of drug action, ERs
      alpha and beta, are the two receptors which are responsible for the first step in
      estrogen and SERM action. The SERM binds to the ERs and confers a unique
      conformation to the complex. In a target site which expresses antiestrogenic
      actions, the conformation of the ER is distinctly different from estrogen bound
      ER. The complex recruits protein partners called corepressors to prevent the
      transcription of estrogen responsive genes. In contrast, at a predominantly
      estrogenic site coactivators for estrogen action are recruited. Unfortunately at
      an antiestrogenic site such as breast cancer, long term SERM therapy causes the
      development of acquired resistance. The breast and endometrial tumor cells
      selectively become SERM stimulated. Overexpression of receptor tyrosine kinases,
      HER-2, EGFR and IGFR and the signaling cascades following their activation are
      frequently involved in SERM resistant breast cancers. The aberrantly activated
      PI3K/AKT and MAPK pathways and their cross talk with the genomic components of
      the ER action are implicated in SERM resistance. Other down stream factors of HER
      2 and EGFR signaling, such as PI3K/AKT, MAPK or mTOR pathways has also been found
      to be involved in resistance mechanisms. Blocking the actions of HER-2 and EGFR
      represent a rational strategy for treating SERM resistant phenotypes and may in
      fact restore the sensitivity to the SERMs. Another approach exploits the
      discovery that low dose estrogen will induce apoptosis in the SERM resistant
      breast cancers. Numerous clinical studies are addressing these issues.

PMID- 18637494
TI  - Pharmacogenomics of endocrine therapy in breast cancer.
AB  - The treatment of breast cancer with selective estrogen receptor modulators such
      as tamoxifen and with aromatase inhibitors represents a major advance in cancer
      chemotherapy. However, there are large variations among patients in both the
      therapeutic efficacy and side effects of these drugs. Pharmacogenomics is the
      study of the role of inheritance in this variation and genetic variation in
      tamoxifen response represents one of the most striking examples of the potential
      clinical importance of pharmacogenomics. Tamoxifen requires "metabolic
      activation" catalyzed by cytochrome P450 2D6 (CYP2D6) to form hydroxylated
      metabolites-4-hydroxytamoxifen and endoxifen (N-desmethyl-4-hydroxytamoxifen)
      both of which are much more potent than is the parent drug. However, CYP2D6 is
      genetically polymorphic. Approximately 5-8% of Caucasian subjects are CYP2D6
      "poor metabolizers" on a genetic basis and, as a result, are relatively unable to
      catalyze tamoxifen hydroxylation. These same subjects appear to have poorer
      outcomes when treated with tamoxifen than do CYP2D6 "extensive metabolizers:
      These data led the US Food and Drug Administration (FDA) to hold public hearings
      in 2006 on the inclusion of this pharmacogenomic information in tamoxifen
      labeling. However, a series of important questions still remains to be addressed
      with regard to tamoxifen pharmacogenomics. There have also been preliminary
      attempts to study the pharmacogenomics ofaromatase inhibitors, including the
      application of a genotype-to-phenotype research strategy designed to explore the
      nature and extent of common DNA sequence variation in the CYP19 gene that encodes
      aromatase. Those results-together with our current level of understanding of
      tamoxifen pharmacogenomics-will be reviewed in this chapter and both will be
      placed within the context of the overall development of pharmacogenomics.

PMID- 18637495
TI  - Prevention of breast cancer using SERMs.
AB  - The development of breast cancer is dependant in part on oestrogen. Suppression
      of ovarian function or use of anti-oestrogens will reduce the incidence of breast
      cancer. Many trials have now been done involving tens of thousands of healthy
      women evaluating the use of selective oestrogen receptor modulators to reduce the
      risk of breast cancer in healthy women. Tamoxifen will reduce the early incidence
      of breast cancer in pre and postmenopausal women by about 40% but causes
      vasomotor symptoms, thromboembolism and gynaecological toxicity including polyps,
      endometrial atypia and rarely cancer. In long follow up trials the risk reduction
      for breast cancer extends beyond the treatment period out to at least 15 years
      appearing to get larger with time indicating a true long term prevention effect.
      The toxicity of tamoxifen is for the most part confined to the treatment period.
      Raloxifene also has similar breast cancer risk reduction activity to tamoxifen
      but has less toxicity with no evidence of an increased risk of endometrial atypia
      or cancer. Tamoxifen is licensed for breast cancer risk reduction in the USA and
      raloxifene has also recently been approved by the FDA for such use.

PMID- 18637496
TI  - Human cytomegalovirus. Preface.

PMID- 18637497
TI  - Human cytomegalovirus genome.
AB  - Human cytomegalovirus (HCMV) contains a large and complex E-type genome. There
      are both clinical isolates of the virus that have been passaged minimally in
      fibroblasts and so-called laboratory strains that have been extensively passaged
      and adapted to growth in fibroblasts. The genomes of laboratory strains have
      undergone rearrangements. To date, the genomes of five clinical isolates have
      been sequenced. We have re-evaluated the coding content of clinical isolates by
      identifying the set of open reading frames (ORFs) that are conserved in all five
      sequenced clinical isolates. We have further determined which of these ORFs are
      present in the chimpanzee cytomegalovirus (CCMV) genome. A total of 173 ORFs are
      present in all HCMV genomes and the CCMV genome, and we conclude that these ORFs
      are very likely to be functional. An additional 59 ORFs are present in the
      genomes of all five HCMV isolates, but not in CCMV. We have discounted 26 of this
      latter set of ORFs, because they reside in regions of the genome unlikely to
      encode functional ORFs. The remaining 33 ORFs are potentially functional ORFs
      that are specific to HCMV.

PMID- 18637498
TI  - Human cytomegalovirus microRNAs.
AB  - MicroRNAs (miRNAs) are approximately 22 nucleotide RNAs that mediate the
      posttranscriptional regulation of gene expression. miRNAs regulate diverse
      cellular processes such as development, differentiation, cell cycling, apoptosis,
      and immune responses. More than 400 miRNAs have been identified in humans and it
      is predicted that over 30% of human gene transcripts are regulated via miRNAs.
      Since 2004, many viral miRNAs have been described in several families of viruses.
      More than half of currently known viral miRNAs are encoded by viruses of the
      human Herepsviridae and 14 miRNAs have been found to be encoded by Human
      cytomegalovirus (HCMV). Thus far, HCMV is the only betaherpesvirus in which
      miRNAs have been described and these miRNAs possess many characteristics,
      including their genomic arrangement and temporal/spatial expression, which
      distinguish them from the other known herpesvirus miRNAs described. As a
      herpesvirus, HCMV establishes infection for the life of the host characterized by
      latent infection with periodic reactivation for production and spread of
      infectious progeny. This multifaceted life cycle of the herpesvirus requires an
      abundance of gene products and regulatory elements that makes cytomegalovirus
      genomes one of the most complex among human viruses. The defining characteristics
      of the cytomegalovirus and the minimal impact on genome size afforded by miRNAs
      inform the logic of virus-encoded miRNAs.

PMID- 18637499
TI  - Mutagenesis of the cytomegalovirus genome.
AB  - Bacterial artificial chromosomes (BACs) are DNA molecules assembled in vitro from
      defined constituents and are stably maintained as one large DNA fragment in
      Escherichia coli. Artificial chromosomes are useful for genome sequencing
      programs, for transduction of DNA segments into eukaryotic cells, and for
      functional characterization of genomic regions and entire viral genomes such as
      cytomegalovirus (CMV) genomes. CMV genomes in BACs are ready for the advanced
      tools of E. coli genetics. Homologous and site-specific recombination, or
      transposon-based approaches allow for the engineering of virtually any kind of
      genetic change.

PMID- 18637500
TI  - Cytomegalovirus cell tropism.
AB  - The human cytomegalovirus (HCMV) can infect a remarkably broad cell range within
      its host, including parenchymal cells and connective tissue cells of virtually
      any organ and various hematopoietic cell types. Epithelial cells, endothelial
      cells, fibroblasts and smooth muscle cells are the predominant targets for virus
      replication. The pathogenesis of acute HCMV infections is greatly influenced by
      this broad target cell range. Infection of epithelial cells presumably
      contributes to inter-host transmission. Infection of endothelial cells and
      hematopoietic cells facilitates systemic spread within the host. Infection of
      ubiquitous cell types such as fibroblasts and smooth muscle cells provides the
      platform for efficient proliferation of the virus. The tropism for endothelial
      cells, macrophages and dendritic cells varies greatly among different HCMV
      strains, mostly dependent on alterations within the UL128-131 gene locus. In line
      with the classification of the respective proteins as structural components of
      the viral envelope, interstrain differences concerning the infectivity in
      endothelial cells and macrophages are regulated on the level of viral entry.

PMID- 18637501
TI  - Virus entry and innate immune activation.
AB  - Human cytomegalovirus (HCMV) exhibits an exceptionally broad cellular tropism as
      it is capable of infecting most major organ systems and cell types. Definitive
      proof of an essential role for a cellular molecule that serves as an entry
      receptor has proven very challenging. It is widely hypothesized that receptor
      utilization, envelope glycoprotein requirements and entry pathways may all vary
      according to cell type, which is partially supported by the data. What has
      clearly emerged in recent years is that virus entry is not going undetected by
      the host. Robust and rapid induction of innate immune response is intimately
      associated with entry-related events. Here we review the state of knowledge on
      HCMV cellular entry mediators confronting the scientific challenges by accruing a
      definitive data set. We also review the roles of pattern recognition receptors
      such as Toll-like receptors in activation of specific innate immune response and
      discuss how entry events are tightly coordinated with innate immune initiation
      steps.

PMID- 18637502
TI  - Functions of human cytomegalovirus tegument proteins prior to immediate early
      gene expression.
AB  - Proteins within the tegument layer of herpesviruses such as human cytomegalovirus
      (HCMV) are released into the cell upon entry when the viral envelope fuses with
      the cell membrane. These proteins are fully formed and active, and they mediate
      key events at the very start of the lytic infectious cycle, including the
      delivery of the viral genome to the nucleus and the initiation of viral gene
      expression. This review examines what is known about tegument protein function
      prior to the immediate early (IE) phase of the viral lytic replication cycle and
      identifies key questions that need to be answered to better understand how these
      proteins promote HCMV infection so that antiviral treatments that target these
      important viral regulators can be developed.

PMID- 18637503
TI  - Initiation of cytomegalovirus infection at ND10.
AB  - As a large double-stranded DNA virus, CMV replicates in the nucleus, a highly
      structured environment. Diffusional and solid phases exist as interdependent sets
      of interactions between many components that determine either replicative success
      of an infecting virus or the defensive success of the host cell. In their
      extremes, cell death may be part of the lytic release of viral particles, or, in
      defense terms, the ultimate sacrifice preventing virus release. Between these
      extremes exists an evolutionarily derived standoff between virus and cell.
      Exogenous shifts in homeostasis can disturb this balance, diminishing the cell's
      defensive powers and reactivating the silenced viral genome. Many of the solid
      phase aspects of this process can be seen in situ and analyzed. This review
      evaluates structural information derived from CMV-infected cells in situ at very
      early times of infection and the conceptional advances derived from them, mostly
      centering on the major immediate early gene products, specifically IE1. A
      scientific basis for considering the major immediate early proteins as potential
      targets in suppressing CMV disease is discussed.

PMID- 18637504
TI  - Functional roles of the human cytomegalovirus essential IE86 protein.
AB  - The IE86 protein of human cytomegalovirus (HCMV) is unique among viral and
      cellular proteins because it negatively autoregulates its own expression,
      activates the viral early and late promoters, and both activates and inhibits
      cellular promoters. It promotes cell cycle progression from Go/G1 to G1/S and
      arrests cell cycle progression at the G1/S interface or at G2/M. The IE86 protein
      is essential because it creates a cellular environment favorable for viral
      replication. The multiple functions of the IE86 protein during the replication of
      HCMV are reviewed.

PMID- 18637505
TI  - Nuts and bolts of human cytomegalovirus lytic DNA replication.
AB  - HCMV lytic DNA replication is complex and highly regulated. The cis-acting lytic
      origin of DNA replication (oriLyt) contains multiple repeat motifs that comprise
      two main functional domains. The first is a bidirectional promoter element that
      is responsive to UL84 and IE2. The second appears to be an RNA/DNA hybrid region
      that is a substrate for UL84. UL84 is required for oriLyt-dependent DNA
      replication along with the six core proteins, UL44 (DNA processivity factor),
      UL54 (DNA polymerase), UL70 (primase), UL105 (helicase), UL102 (primase
      associated factor) and UL57 (single-stranded DNA-binding protein). UL84 is an
      early protein that shuttles from the nucleus to the cytoplasm, binds RNA,
      suppresses the transcriptional activation function of IE2, has UTPase activity
      and is proposed to be a member of the DExH/D box family of proteins. UL84 is a
      key factor that may act in concert with the other core replication proteins to
      initiate lytic replication by altering the conformation of an RNA stem loop
      structure within oriLyt. In addition, new data suggests that UL84 interacts with
      at least one member of the viral replication proteins and several cellular
      encoded proteins.

PMID- 18637506
TI  - Interactions of human cytomegalovirus proteins with the nuclear transport
      machinery.
AB  - Accurate cellular localization is crucial for the effective function of most
      viral macromolecules and nuclear translocation is central to the function of
      herpesviral proteins that are involved in processes such as transcription and DNA
      replication. The passage of large molecules between the cytoplasm and nucleus,
      however, is restricted, and this restriction affords specific mechanisms that
      control nucleocytoplasmic exchange. In this review, we focus on two
      cytomegalovirus-encoded proteins, pUL69 and pUL84, that are able to shuttle
      between the nucleus and the cytoplasm. Both viral proteins use unconventional
      interactions with components of the cellular transport machinery: pUL69 binds to
      the mRNA export factor UAP56, and this interaction is crucial for pUL69-mediated
      nuclear export of unspliced RNA; pUL84 docks to importin-alpha proteins via an
      unusually large protein domain that contains functional leucine-rich nuclear
      export signals, thus serving as a complex bidirectional transport domain.
      Selective interference with these unconventional interactions, which disturbs the
      intracellular trafficking of important viral regulatory proteins, may constitute
      a novel and attractive principle for antiviral therapy.

PMID- 18637507
TI  - Structure and formation of the cytomegalovirus virion.
AB  - Transport and protection of the nuclear-replicating double-stranded DNA genome of
      herpesviruses is accomplished by the virion and its substructures. Studies of the
      composition, organization, and formation of these particles have provided insight
      into the molecular mechanisms of virus assembly, leads for antiviral strategies,
      and information about cellular processes that are required for, resemble, or
      antagonize virus replication. This chapter updates earlier reviews on the
      structure and formation human cytomegalovirus (HCMV) virions (Gibson 1996, 2006;
      Eickmann et al. 2006), and complements several other reviews on herpesvirus
      structure and replication presented in this volume (see the chapters by E. Murphy
      and T. Shenk, Z. Ruzsics and U. Koszinowski, R. Kalejta, and G.S. Pari) and
      elsewhere (Rixon 1993; Steven and Spear 1997; Brown et al. 2002; Varnum et al.
      2004; Liu and Zhou 2007).

PMID- 18637508
TI  - Human cytomegalovirus modulation of signal transduction.
AB  - An upregulation of cellular signaling pathways is observed in multiple cell types
      upon human cytomegalovirus (HCMV) infection, suggesting that a global feature of
      HCMV infection is the activation of the host cell. HCMV initiates and maintains
      cellular signaling through a multitiered process that is dependent on a series of
      events: (1) the viral glycoprotein ligand interacts with its cognate receptor,
      (2) cellular enzymes and viral tegument proteins present in the incoming virion
      are released and (3) a variety of viral gene products are expressed. Viral
      mediated cellular modification has differential outcomes depending on the cell
      type infected. In permissive cell types, such as diploid fibroblasts, the
      upregulation of cellular signaling pathways following infection can initiate the
      viral gene cascade and promote the efficient transcription of multiple viral gene
      classes. In other cell types, such as endothelial cells and
      monocytes/macrophages, the upregulation of cellular pathways initiates functional
      host changes that allow viral spread to multiple organ systems. Together, the
      modification of signaling processes appears to be part of a thematic strategy
      deployed by the virus to direct the required functional changes in target cells
      that ultimately promote viral survival and persistence in the host.

PMID- 18637509
TI  - Chemokines and chemokine receptors encoded by cytomegaloviruses.
AB  - CMVs carry several genes that are homologous to genes of the host organism. These
      include genes homologous to those encoding chemokines (CKs) and G protein-coupled
      receptors (GPCRs). It is generally assumed that these CMV genes were hijacked
      from the host genome during the long co-evolution of virus and host. In light of
      the important function of the CK and GPCR families in the normal physiology of
      the host, it has previously been hypothesized that the CMV homologs of these
      proteins, CMV vCKs and vGPCRs, may also have a significant impact on this
      physiology, such that lifelong maintenance and/or replication of the virus within
      the infected host is guaranteed. In addition, several of these homologs were
      reported to have a major impact in the pathogenesis of infection. In this review,
      the current state of knowledge on the CMV vCKs and vGPCRs will be discussed.

PMID- 18637510
TI  - Subversion of cell cycle regulatory pathways.
AB  - Human cytomegalovirus (HCMV) has evolved numerous strategies to commandeer the
      host cell for producing viral progeny. The virus manipulates host cell cycle
      pathways from the early stages of infection to stimulate viral DNA replication at
      the expense of cellular DNA synthesis. At the same time, cell cycle checkpoints
      are by-passed, preventing apoptosis and allowing sufficient time for the assembly
      of infectious virus.

PMID- 18637511
TI  - Modulation of host cell stress responses by human cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) induces cellular stress responses during infection
      due to nutrient depletion, energy depletion, hypoxia and synthetic stress, e.g.,
      endoplasmic reticulum (ER) stress. Cellular stress responses initiate processes
      that allow the cell to survive the stress; some of these may be beneficial to
      HCMV replication while others are not. Several studies show that HCMV manipulates
      stress response signaling in order to maintain beneficial effects while
      inhibiting detrimental effects. The inhibition of translation is the most common
      effect of stress responses that would be detrimental to HCMV infection. This
      chapter will focus on the mechanisms by which cap-dependent translation is
      maintained during HCMV infection through alterations of the phosphatidylinositol
      3' kinase (PI3K)-Akt-tuberous sclerosis complex (TSC)-mammalian target of
      rapamycin (mTOR) signaling pathway. The emerging picture is that HCMV affects
      this pathway in multiple ways, thus ensuring that cap-dependent translation is
      maintained despite the induction of stress responses that would normally inhibit
      it. Such dramatic alterations of this pathway lead to questions of what other
      beneficial effects the virus might gain from these changes and how these changes
      may contribute to HCMV pathogenesis.

PMID- 18637512
TI  - Control of apoptosis by human cytomegalovirus.
AB  - Caspase-dependent apoptosis has an important role in controlling viruses, and as
      a result, viruses often encode proteins that target this pathway. Caspase
      dependent apoptosis can be activated from within the infected cell as an
      intrinsic response to replication-associated stresses or through death-inducing
      signals produced extrinsically by immune cells. Cytomegaloviruses (CMVs) encode a
      mitochondria-localized inhibitor of apoptosis, vMIA, and a viral inhibitor of
      caspase activation, vICA, the functional homologs of Bcl-2 related and c-FLIP
      proteins, respectively. Evidence from viral mutants deleting either vMIA or vICA
      suggests that each is necessary and sufficient to promote survival of infected
      cells undergoing caspase-dependent apoptosis. Additional proteins, including
      pUL38, IE1(491a), and IE2(579aa), can prevent apoptosis induced by various
      stimuli, while viruses with deletions of UL38, M45, or m41 undergo apoptosis. The
      viral RNA, beta2.7, binds mitochondrial respiratory complex I, maintains ATP
      production late in infection, and prevents death induced by a mitochondrial
      poison. Thus, CMV alters cell intrinsic defenses employing apoptosis, and
      multiple viral gene products together control death-inducing stimuli to promote
      survival.

PMID- 18637513
TI  - Aspects of human cytomegalovirus latency and reactivation.
AB  - Primary infection of healthy individuals with human cytomegalovirus (HCMV) is
      usually asymptomatic and results in the establishment of a lifelong latent
      infection of the host. Although no overt HCMV disease is observed in healthy
      carriers, due to effective immune control, severe clinical symptoms associated
      with HCMV reactivation are observed in immunocompromised transplant patients and
      HIV sufferers. Work from a number of laboratories has identified the myeloid
      lineage as one important site for HCMV latency and reactivation and thus has been
      the subject of extensive study. Attempts to elucidate the mechanisms controlling
      viral latency have shown that cellular transcription factors and histone proteins
      influence HCMV gene expression profoundly and that the type of cellular
      environment virus encounters upon infection may have a critical role in
      determining a lytic or latent infection and subsequent reactivation from latency.
      Furthermore, the identification of a number of viral gene products expressed
      during latent infection suggests a more active role for HCMV during latency.
      Defining the role of these viral proteins in latently infected cells will be
      important for our full understanding of HCMV latency and reactivation in vivo.

PMID- 18637514
TI  - Murine model of cytomegalovirus latency and reactivation.
AB  - Efficient resolution of acute cytopathogenic cytomegalovirus infection through
      innate and adaptive host immune mechanisms is followed by lifelong maintenance of
      the viral genome in host tissues in a state of replicative latency, which is
      interrupted by episodes of virus reactivation for transmission. The establishment
      of latency is the result of aeons of co-evolution of cytomegaloviruses and their
      respective host species. Genetic adaptation of a particular cytomegalovirus to
      its specific host is reflected by private gene families not found in other
      members of the cytomegalovirus group, whereas basic functions of the viral
      replicative cycle are encoded by public gene families shared between different
      cytomegaloviruses or even with herpesviruses in general. Private genes include
      genes coding for immunoevasins, a group of glycoproteins specifically dedicated
      to dampen recognition by the host's innate and adaptive immune surveillance to
      protect the virus against elimination. Recent data in the mouse model of
      cytomegalovirus latency have indicated that viral replicative latency established
      in the immunocompetent host is a dynamic state characterized by episodes of viral
      gene desilencing and immune sensing of reactivated presentation of antigenic
      peptides at immunological checkpoints by CD8 T cells. This sensing maintains
      viral replicative latency by triggering antiviral effector functions that
      terminate the viral gene expression program before infectious viral progeny are
      assembled. According to the immune sensing hypothesis of latency control,
      immunological checkpoints are unique for each infected individual in reflection
      of host MHC (HLA) polymorphism and the proteome(s) of the viral variant(s)
      harbored in latency.

PMID- 18637515
TI  - Cytomegalovirus immune evasion.
AB  - Human cytomegalovirus (HCMV) has become a paradigm for viral immune evasion due
      to its unique multitude of immune-modulatory strategies. HCMV modulates the
      innate as well as adaptive immune response at every step of its life cycle. It
      dampens the induction of antiviral interferon-induced genes by several
      mechanisms. Further striking is the multitude of genes and strategies devoted to
      modulating and escaping the cellular immune response. Several genes are
      independently capable of inhibiting antigen presentation to cytolytic T cells by
      downregulating MHC class I. Recent data revealed an astounding variety of methods
      in triggering or inhibiting activatory and inhibitory receptors found on NK
      cells, NKT cells, T cells as well as auxiliary cells of the immune system. The
      multitude and complexity of these mechanisms is fascinating and continues to
      reveal novel insights into the host-pathogen interaction and novel cell
      biological and immunological concepts.

PMID- 18637516
TI  - Cytomegalovirus vaccine development.
AB  - Although infection with human cytomegalovirus (HCMV) is ubiquitous and usually
      asymptomatic, there are individuals at high risk for serious HCMV disease. These
      include solid organ and hematopoietic stem cell (HSC) transplant patients,
      individuals with HIV infection, and the fetus. Since immunity to HCMV ameliorates
      the severity of disease, there have been efforts made for over 30 years to
      develop vaccines for use in these high-risk settings. However, in spite of these
      efforts, no HCMV vaccine appears to be approaching imminent licensure. The
      reasons for the failure to achieve the goal of a licensed HCMV vaccine are
      complex, but several key problems stand out. First, the host immune correlates of
      protective immunity are not yet clear. Secondly, the viral proteins that should
      be included in a HCMV vaccine are uncertain. Third, clinical trials have largely
      focused on immunocompromised patients, a population that may not be relevant to
      the problem of protection of the fetus against congenital infection. Fourth, the
      ultimate target population for HCMV vaccination remains unclear. Finally, and
      most importantly, there has been insufficient education about the problem of HCMV
      infection, particularly among women of child-bearing age and in the lay public.
      This review considers the strategies that have been explored to date in
      development of HCMV vaccines, and summarizes both active clinical trials as well
      as novel technologies that merit future consideration toward the goal of
      prevention of this significant public health problem.

PMID- 18637517
TI  - Cytomegalovirus infection in the human placenta: maternal immunity and
      developmentally regulated receptors on trophoblasts converge.
AB  - During human pregnancy, CMV infects the uterine-placental interface with varied
      outcomes from fetal intrauterine growth restriction to permanent birth defects,
      depending on the level of maternal immunity and gestational age. Virus spreads
      from infected uterine blood vessels, amplifies by replicating in decidual cells,
      and disseminates to the placenta in immune complexes. Cytotrophoblasts-
      epithelial cells of the placenta--differentiate along two distinct pathways. In
      the first, cells fuse into syncytiotrophoblasts covering the surface of chorionic
      villi that transport substances from the maternal to fetal bloodstream. In the
      second, cells invade the uterine interstitium and blood vessels, remodel the
      vasculature and form anchoring villi. CMV initiates replication in
      cytotrophoblast progenitor cells of floating villi, whereas syncytiotrophoblasts
      are spared. This extraordinary pattern of focal infection in underlying cells
      hinges on virion receptors being upregulated as villous cytotrophoblasts begin to
      differentiate. Expression of developmentally regulated receptors could explain
      viral replication in spatially distinct maternal and fetal compartments. Reduced
      invasiveness of infected cells could impair remodeling of the uterine
      vasculature, restrict maternal blood flow and access of the fetus to nutrients
      causing intrauterine growth restriction.

PMID- 18637519
TI  - Manifestations of human cytomegalovirus infection: proposed mechanisms of acute
      and chronic disease.
AB  - Infections with human cytomegalovirus (HCMV) are a major cause of morbidity and
      mortality in humans with acquired or developmental deficits in innate and
      adaptive immunity. In the normal immunocompetent host, symptoms rarely accompany
      acute infections, although prolonged virus shedding is frequent. Virus
      persistence is established in all infected individuals and appears to be
      maintained by both a chronic productive infections as well as latency with
      restricted viral gene expression. The contributions of the each of these
      mechanisms to the persistence of this virus in the individual is unknown but
      frequent virus shedding into the saliva and genitourinary tract likely accounts
      for the near universal incidence of infection in most populations in the world.
      The pathogenesis of disease associated with acute HCMV infection is most readily
      attributable to lytic virus replication and end organ damage either secondary to
      virus replication and cell death or from host immunological responses that target
      virus-infected cells. Antiviral agents limit the severity of disease associated
      with acute HCMV infections, suggesting a requirement for virus replication in
      clinical syndromes associated with acute infection. End organ disease secondary
      to unchecked virus replication can be observed in infants infected in utero,
      allograft recipients receiving potent immunosuppressive agents, and patients with
      HIV infections that exhibit a loss of adaptive immune function. In contrast,
      diseases associated with chronic or persistent infections appear in normal
      individuals and in the allografts of the transplant recipient. The manifestations
      of these infections appear related to chronic inflammation, but it is unclear if
      poorly controlled virus replication is necessary for the different phenotypic
      expressions of disease that are reported in these patients. Although the
      relationship between HCMV infection and chronic allograft rejection is well
      known, the mechanisms that account for the role of this virus in graft loss are
      not well understood. However, the capacity of this virus to persist in the midst
      of intense inflammation suggests that its persistence could serve as a trigger
      for the induction of host-vs-graft responses or alternatively host responses to
      HCMV could contribute to the inflammatory milieu characteristic of chronic
      allograft rejection.

PMID- 18637518
TI  - Mechanisms of cytomegalovirus-accelerated vascular disease: induction of
      paracrine factors that promote angiogenesis and wound healing.
AB  - Human cytomegalovirus (HCMV) is associated with the acceleration of a number of
      vascular diseases such as atherosclerosis, restenosis, and transplant vascular
      sclerosis (TVS). All of these diseases are the result of either mechanical or
      immune-mediated injury followed by inflammation and subsequent smooth muscle cell
      (SMC) migration from the vessel media to the intima and proliferation that
      culminates in vessel narrowing. A number of epidemiological and animal studies
      have demonstrated that CMV significantly accelerates TVS and chronic rejection
      (CR) in solid organ allografts. In addition, treatment of human recipients and
      animals alike with the antiviral drug ganciclovir results in prolonged survival
      of the allograft, indicating that CMV replication is a requirement for
      acceleration of disease. However, although virus persists in the allograft
      throughout the course of disease, the number of directly infected cells does not
      account for the global effects that the virus has on the acceleration of TVS and
      CR. Recent investigations of up- and downregulated cellular genes in infected
      allografts in comparison to native heart has demonstrated that rat CMV (RCMV)
      upregulates genes involved in wound healing (WH) and angiogenesis (AG).
      Consistent with this result, we have found that supernatants from HCMV-infected
      cells (HCMV secretome) induce WH and AG using in vitro models. Taken together,
      these findings suggest that one mechanism for HCMV acceleration of TVS is
      mediated through induction of secreted cytokines and growth factors from virus
      infected cells that promote WH and AG in the allograft, resulting in the
      acceleration of TVS. We review here the ability of CMV infection to alter the
      local environment by producing cellular factors that act in a paracrine fashion
      to enhance WH and AG processes associated with the development of vascular
      disease, which accelerates chronic allograft rejection.

PMID- 18637520
TI  - Diverse roles of integrin receptors in articular cartilage.
AB  - Integrins are heterodimeric integral membrane proteins made up of alpha and beta
      subunits. At least eighteen alpha and eight beta subunit genes have been
      described in mammals. Integrin family members are plasma membrane receptors
      involved in cell adhesion and active as intra- and extracellular signalling
      molecules in a variety of processes including embryogenesis, hemostasis, tissue
      repair, immune response and metastatic spread of tumour cells. Integrin beta 1
      (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and
      VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell
      signalling, cellular defense, cell adhesion, protein binding, protein
      heterodimerisation and receptor-mediated activity. It is highly expressed in the
      human body (17.4 times higher than the average gene in the last updated revision
      of the human genome). The extracellular matrix (ECM) of articular cartilage is a
      unique environment. Interactions between chondrocytes and the ECM regulate many
      biological processes important to homeostasis and repair of articular cartilage,
      including cell attachment, growth, differentiation and survival. The beta1
      integrin family of cell surface receptors appears to play a major role in
      mediating cell-matrix interactions that are important in regulating these
      fundamental processes. Chondrocyte mechanoreceptors have been proposed to
      incorporate beta1-integrins and mechanosensitive ion channels which link with key
      ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype,
      prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression.
      This review focuses on the expression and function of beta1-integrins in
      articular chondrocytes, its role in the unique biology of these cells and its
      distribution in cartilage.

PMID- 18637521
TI  - The role of Wnt signalling in the development of somites and neural crest.
AB  - The Wnt family of secreted signalling molecules controls a wide range of
      developmental processes in all metazoans. In this investigation we concentrate on
      the role that members of this family play during the development of (1) the
      somites and (2) the neural crest. (3) We also isolate a novel component of the
      Wnt signalling pathway called Naked cuticle and investigate the role that this
      protein may play in both of the previously mentioned developmental processes. (1)
      In higher vertebrates the paraxial mesoderm undergoes a mesenchymal-to-epithelial
      transformation to form segmentally organised structures called somites.
      Experiments have shown that signals originating from the ectoderm overlying the
      somites or from midline structures are required for the formation of the somites,
      but their identity has yet to be determined. Wnt6 is a good candidate as a somite
      epithelialisation factor from the ectoderm since it is expressed in this tissue.
      In this study we show that injection of Wnt6-producing cells beneath the ectoderm
      at the level of the segmental plate or lateral to the segmental plate leads to
      the formation of numerous small epithelial somites. We show that Wnts are indeed
      responsible for the epithelialisation of somites by applying Wnt antagonists
      which result in the segmental plate being unable to form somites. These results
      show that Wnt6, the only member of this family to be localised to the chick
      paraxial ectoderm, is able to regulate the development of epithelial somites and
      that cellular organisation is pivotal in the execution of the differentiation
      programmes. (2) The neural crest is a population of multipotent progenitor cells
      that arise from the neural ectoderm in all vertebrate embryos and form a
      multitude of derivatives including the peripheral sensory neurons, the enteric
      nervous system, Schwann cells, pigment cells and parts of the craniofacial
      skeleton. The induction of the neural crest relies on an ectodermally derived
      signal, but the identity of the molecule performing this role in amniotes is not
      known. Here we show that Wnt6, a protein expressed in the ectoderm, induces
      neural crest production. (3) The intracellular response to Wnt signalling depends
      on the choice of signalling cascade activated in the responding cell. Cells can
      activate either the canonical pathway that modulates gene expression to control
      cellular differentiation and proliferation, or the non-canonical pathway that
      controls cell polarity and movement (Pandur et al. 2002b). Recent work has
      identified the protein Naked cuticle as an intracellular switch promoting the non
      canonical pathway at the expense of the canonical pathway. We have cloned chick
      Naked cuticle-1 (cNkd1) and demonstrate that it is expressed in a dynamic manner
      during early embryogenesis. We show that it is expressed in the somites and in
      particular regions where cells are undergoing movement. Lastly our study shows
      that the expression of cNkd1 is regulated by Wnt expression originating from the
      neural tube. This study provides evidence that non-canonical Wnt signalling plays
      a part in somite development.

PMID- 18637522
TI  - Factors influencing mammalian kidney development: implications for health in
      adult life.
AB  - There are many reasons why it is timely to review the development of the
      mammalian kidney. Perhaps the most important of these is the increasing amount of
      evidence to demonstrate that factors which impinge on/alter the normal
      developmental processes of this organ can have lifelong consequences for the
      health of the adult. The'Developmental Origins of Health and Adult Disease'
      (DOHaD) hypothesis, proposes that changes in the environment during the
      development of an organ or system, can have permanent deleterious effects leading
      to increased risk of cardiovascular and/or metabolic disease. The permanent
      metanephric kidney has been shown to be very vulnerable to such influences with
      many factors shown to alter both the permanent structure and the level of
      expression of important functional genes. Thus it is important to understand the
      precise timing of kidney development in terms of both structure and the genes
      involved at each stage. Such knowledge has been gained by significant advances in
      technology, which allow quantification of the number of nephrons by unbiased
      stereology, detections of both levels and site of gene expression,'knock-out' and
      knock-in' of genes in animal (mainly mouse) models and by the ability to examine
      nephron development, in real time, in culture systems.

PMID- 18637524
TI  - Early-life risk factors for adult chronic disease: follow-up of a cohort born
      during 1964-1978 in an urban slum of Lahore, Pakistan.
AB  - Evidence suggests that risk of chronic diseases may be programmed during the
      foetal and early life of the infant. With high rates of low birthweight coupled
      with a rapid nutritional transition, low-income countries are facing an epidemic
      of chronic diseases. Follow-up of a cohort of adults born during 1964-1978 in an
      urban slum in Lahore, Pakistan, is presented in this paper. In 695 of these
      adults (mean age=29.0 years, males=56%), blood pressure, fasting blood glucose,
      and body mass index (BMI) were measured to assess early-life predictors of risk
      of chronic diseases. Sixteen percent of the study population was born with a low
      birthweight (<2,500 g). A significant positive association (p=0.007) was observed
      between birthweight and BMI; additionally, adjusting for age and gender, the
      association with BMI was highly significant (p=0.000). Conversely, a significant
      negative association (p=0.016) was observed between birthweight and adult levels
      of fasting plasma glucose; after adjustment for age and gender, the association
      was more significant (p=0.005) No association was observed between birthweight
      and adult blood pressure. The results suggest that low birthweight may increase
      later risk of impaired glucose tolerance in urban Pakistani adults. Further
      research in this area is warranted.

PMID- 18637523
TI  - Effect of HIV/AIDS and malaria on the context for introduction of zinc treatment
      and low-osmolarity ORS for childhood diarrhoea.
AB  - Diarrhoea was estimated to account for 18% of the estimated 10.6 million deaths
      of children aged less than five years annually in 2003. Two--Africa and South
      East Asia--of the six regions of the World Health Organization accounted for
      approximately 40% and 31% of these deaths respectively, or almost three-quarters
      of the global annual deaths of children aged less than five years attributable to
      diarrhoea. Much of the effort to roll out low-osmolarity oral rehydration
      solution (ORS) and supplementation of zinc for the management of diarrhoea
      accordingly is being devoted to sub-Saharan Africa and to South and South-East
      Asia. A number of significant differences exist in diarrhoea-treatment behaviours
      and challenges of the public-health systems between Africa and Asia. The
      differences in rates of ORS use are the most common indicator of treatment of
      diarrhoea and vary dramatically by and within region and may significantly
      influence the roll-out strategy for zinc and low-osmolarity ORS. The prevalence
      of HIV/AIDS and the endemicity of malaria also differ greatly between regions;
      both the diseases consume the attention and financial commitment of public-health
      programmes in regions where rates are high. This paper examined how these
      differences could affect the context for the introduction of zinc and low
      osmolarity ORS at various levels, including the process of policy dialogue with
      local decision-makers, questions to be addressed in formative research,
      implementation approaches, and strategies for behaviour-change communication and
      training of health workers.

PMID- 18637525
TI  - Sex and socioeconomic differentials in child health in rural Bangladesh: findings
      from a baseline survey for evaluating Integrated Management of Childhood Illness.
AB  - This paper reports on a population-based sample survey of 2,289 children aged
      less than five years (under-five children) conducted in 2000 as a baseline for
      the Bangladesh component of the Multi-country Evaluation (MCE) of the Integrated
      Management of Childhood Illness strategy. Of interest were rates and
      differentials by sex and socioeconomic status for three aspects of child health
      in rural Bangladesh: morbidity and hospitalizations, including severity of
      illness; care-seeking for childhood illness; and home-care for illness. The
      survey was carried out among a population of about 380,000 in Matlab upazila
      (subdistrict). Generic MCE Household Survey tools were adapted, translated, and
      pretested. Trained interviewers conducted the survey in the study areas. In
      total, 2,289 under-five children were included in the survey. Results showed a
      very high prevalence of illness among Bangladeshi children, with over two-thirds
      reported to have had at least one illness during the two weeks preceding the
      survey. Most sick children in this population had multiple symptoms, suggesting
      that the use of the IMCI clinical guidelines will lead to improved quality of
      care. Contrary to expectations, there were no significant differences in the
      prevalence of illness either by sex or by socioeconomic status. About one-third
      of the children with a reported illness did not receive any care outside the
      home. Of those for whom outside care was sought, 42% were taken to a village
      doctor. Only 8% were taken to an appropriate provider, i.e. a health facility, a
      hospital, a doctor, a paramedic, or a community-based health worker. Poorer
      children than less-poor children were less likely to be taken to an appropriate
      healthcare provider. The findings indicated that children with severe illness in
      the least poor households were three times more likely to seek care from a
      trained provider than children in the poorest households. Any evidence of gender
      inequities in child healthcare, either in terms of prevalence of illness or care
      seeking patterns, was not found. Care-seeking patterns were associated with the
      perceived severity of illness, the presence of danger signs, and the duration and
      number of symptoms. The results highlight the challenges that will need to be
      addressed as IMCI is implemented in health facilities and extended to address key
      family and community practices, including extremely low rates of use of the
      formal health sector for the management of sick children. Child health planners
      and researchers must find ways to address the apparent population preference for
      untrained and traditional providers which is determined by various factors,
      including the actual and perceived quality of care, and the differentials in care
      seeking practices that discriminate against the poorest households.

PMID- 18637526
TI  - Practices of rural Egyptian birth attendants during the antenatal, intrapartum
      and early neonatal periods.
AB  - Neonatal deaths account for almost two-thirds of infant mortality worldwide; most
      deaths are preventable. Two-thirds of neonatal deaths occur during the first week
      of life, usually at home. While previous Egyptian studies have identified
      provider practices contributing to maternal mortality, none has focused on
      neonatal care. A survey of reported practices of birth attendants was
      administered. Chi-square tests were used for measuring the statistical
      significance of inter-regional differences. In total, 217 recently-delivered
      mothers in rural areas of three governorates were interviewed about antenatal,
      intrapartum and postnatal care they received. This study identified antenatal
      advice of birth attendants to mothers about neonatal care and routine intrapartum
      and postpartum practices. While mothers usually received antenatal care from
      physicians, traditional birth attendants (dayas) conducted most deliveries.
      Advice was rare, except for breastfeeding. Routine practices included hand
      washing by attendants, sterile cord-cutting, prompt wrapping of newborns, and
      postnatal home visits. Suboptimal practices included lack of disinfection of
      delivery instruments, unhygienic cord care, lack of weighing of newborns, and
      lack of administration of eye prophylaxis or vitamin K. One-third of complicated
      deliveries occurred at home, commonly attended by relatives, and the umbilical
      cord was frequently pulled to hasten delivery of the placenta. In facilities,
      mothers reported frequent use of forceps, and asphyxiated neonates were often
      hung upside-down during resuscitation. Consequently, high rates of birth injuries
      were reported. Priority areas for behaviour change and future research to improve
      neonatal health outcomes were identified, specific to type of provider
      (physician, nurse, or daya) and regional variations in practices.

PMID- 18637527
TI  - Factors relating to acceptance of hepatitis B virus vaccination by nursing
      students in a tertiary hospital, Pakistan.
AB  - This cross-sectional study aimed at assessing the prevalence of, and factors
      relating to, the acceptance of hepatitis B virus (HBV) vaccination by nursing
      students in a tertiary hospital in Pakistan. In total, 210 nursing students of
      Year 2 to Year 4 were invited to participate in the study; of them, 196 (93.3%)
      returned completed questionnaires. Overall, the prevalence of acceptance of HBV
      vaccination among them was 75.0%. Of these, 37.2% (73/196) were completely
      vaccinated, and 25.0% (49/196) had not been vaccinated at all. More than half
      (27/49, 55.1%) of the unvaccinated nursing students stated that they would accept
      vaccination if offered. Multiple logistic regression analysis indicated three
      variables significantly related to acceptance of HBV vaccination: history of
      accidental exposure to blood or blood products, acceptable knowledge about HBV
      infection, and adequate budget for HBV vaccination. Health institutions should
      allocate adequate budgets to vaccinate their nursing students. Effective
      intervention programmes designed to increase knowledge about HBV infection and
      adhering to universally-accepted precautions are needed.

PMID- 18637528
TI  - Estimation of individual neonatal survival using birthweight and gestational age:
      a way to improve neonatal care.
AB  - The study was conducted to determine the combined effect of birthweight and
      gestational age at birth on neonatal mortality using individually-identified
      livebirths. Logistic regression was used for studying the interactive effect of
      birthweight and gestational age on the individual probability of neonatal death.
      All livebirths from Chile in 2000 were included in a linked file. Odds ratio
      models for birthweight and gestational age were developed for each sex. The
      probability of neonatal death by sex was presented using contour plots. The
      models were statistically significant, and odds ratios were different and non
      linear for the effects of birthweight and gestational age. Contour plots of
      constant neonatal mortality according to birthweight and gestational age were
      presented; they were similar for each sex. A single graph for both sexes that
      estimates the survival potential of infants born too early or too small would
      improve neonatal care in developing countries.

PMID- 18637529
TI  - Child mortality inequalities and linkage with sanitation facilities in
      Bangladesh.
AB  - Principal component analysis (PCA) was applied to assets and other household
      data, collected as part of the Bangladesh Demographic and Health Survey (BDHS) in
      2004, to rank individuals according to a household socioeconomic index and to
      investigate whether this predicts access to the sanitation system or outcomes.
      PCA was used for determining wealth indices for 11,440 women in 10,500 households
      in Bangladesh. The index was based on the presence or absence of items from a
      list of 13 specific household assets and three housing characteristics. PCA
      revealed 35 components, of which the first component accounted for 18% of the
      total variance. Ownership of assets and housing features contributed almost
      equally to the variance in the first component. In this study, ownership of
      latrines was examined as an example of sanitation-intervention access, and rates
      of mortality of neonates, infant, and children aged less than five years (under
      five mortality) as examples of health outcomes. The analysis demonstrated
      significant gradients in both access and outcome measures across the wealth
      quintiles. The findings call for more attention to approaches for reducing health
      inequalities. These could include reforms in the health sector to provide more
      equitable allocation of resources, improvement in the quality of health services
      offered to the poor, and redesigning interventions and their delivery to ensure
      that they are more pro-poor.

PMID- 18637530
TI  - Effectiveness of weekly supplementation of iron to control anaemia among
      adolescent girls of Nashik, Maharashtra, India.
AB  - A national nutritional anaemia-control programme in India, focusing on
      supplementation of iron to pregnant women after the first trimester of pregnancy,
      failed to make an impact. It is prudent to recommend the correction of iron
      stores before the woman becomes pregnant. 'Efficacy' of weekly supplementation of
      iron has been proved to improve iron stores in adolescence in many studies abroad
      and in India. The objective was to study the 'effectiveness' of a weekly iron
      supplementation regimen among urban-slum, rural, and tribal girls of Nashik
      district, Maharashtra, India. A baseline and the mid-term assessments were done
      using the cluster-sampling techniques. In each stratum, 30 clusters were
      identified. Twelve and 10 adolescent girls from each cluster were identified in
      the baseline and mid-term surveys respectively. The haemoglobin estimation was
      done using the HemoCue system. Data were analyzed using the Epi Info software
      (version 6.04). The overall prevalence of anaemia came down significantly to
      54.3% from 65.3%. The decline was statistically significant (p<0.001) in tribal
      girls (48.6% from 68.9%) and among rural girls (51.6% from 62.8%). But the
      decline was not statistically significant among urban slum girls. Similarly, a
      significant rise in the mean haemoglobin levels was seen among tribal and rural
      girls. However, it did not increase significantly among urban slum girls. The
      programme had performed poorly in urban-slum areas, as the mean number of tablets
      consumed in urban-slum areas was only 5.6+/-3.3, as against 6.7+/-2.6 tablets in
      tribal girls and 7.2+/-2.2 tablets in rural girls. Considering the biological and
      operational feasibility and the effectiveness of the intervention, weekly
      supplementation of iron to adolescent girls should be universally started to
      correct the iron stores of a woman before she becomes pregnant.

PMID- 18637532
TI  - Prevalence of hypertension among high school students in a middle Anatolian
      province of Turkey.
AB  - Hypertension may lead to irreversible damages in vital organs, such as heart,
      brain, and kidney, and may cause death in children if treatments are not given
      despite early diagnosis. This cross-sectional epidemiological study was conducted
      during 1 January-31 March 2004 to investigate the prevalence of hypertension
      among high school students. The study cohort included 1,041 students of six high
      schools, who were selected from among 14,789 students of 26 high schools in Sivas
      province of Turkey, using the cluster-sampling method. A questionnaire was used
      for collecting information from students on age, gender, smoking, and whether
      they or their families have any diseases. Blood pressure, height, and weight of
      the participitants were determined by the research group. Students whose repeated
      systolic or diastolic blood pressures were higher than the 95th percentile were
      considered to be hypertensive patients. Hypertension was prevalent among 4.4%
      (n=45) of the students. There was a significant correlation between prevalence of
      hypertension and body mass index. No significant correlation was found between
      prevalence of hypertension and other variables, such as smoking, age, gender, and
      family history of diabetes. The results suggest that hypertension is an important
      public-health problem among high school students. The results also showed that
      the body mass index was an important parameter in hypertension in such a study
      group. Researchers should consider overweight a causative risk factor for
      development of hypertension in early-onset groups.

PMID- 18637531
TI  - Molecular typing of Vibrio cholerae O1 isolates from Thailand by pulsed-field gel
      electrophoresis.
AB  - The aim of the present study was to genotypically characterize Vibrio cholerae
      strains isolated from cholera patients in various provinces of Thailand. Two
      hundred and forty V. cholerae O1 strains, isolated from patients with cholera
      during two outbreaks, i.e. March 1999-April 2000 and December 2001-February 2002,
      in Thailand, were genotypically characterized by NotI digestion and pulsed-field
      gel electrophoresis (PFGE). In total, 17 PFGE banding patterns were found and
      grouped into four Dice-coefficient clusters (PF-I to PF-IV). The patterns of V.
      cholerae O1, El Tor reference strains from Australia, Peru, Romania, and the
      United States were different from the patterns of reference isolates from Asian
      countries, such as Bangladesh, India, and Thailand, indicating a close genetic
      relationship or clonal origin of the isolates in the same geographical region.
      The Asian reference strains, regardless of their biotypes and serogroups
      (classical O1, El Tor O1, O139, or O151), showed a genetic resemblance, but had
      different patterns from the strains collected during the two outbreaks in
      Thailand. Of 200 Ogawa strains collected during the first outbreak in Thailand,
      two patterns (clones)--PF-I and PF-II--predominated, while other isolates caused
      sporadic cases and were grouped together as pattern PF-III. PF-II also
      predominated during the second outbreak, but none of the 40 isolates (39 Inaba
      and 1 Ogawa) of the second outbreak had the pattern PF-I; a minority showed a new
      pattern--PF-IV, and others caused single cases, but were not groupable. In
      summary, this study documented the sustained appearance of the pathogenic V.
      cholerae O1 clone PF-II, the disappearance of clones PF-I and PF-III, and the
      emergence of new pathogenic clones during the two outbreaks of cholera. Data of
      the study on molecular characteristics of indigenous V. cholerae clinical
      isolates have public-health implications, not only for epidemic tracing of
      existing strains but also for the recognition of strains with new genotypes that
      may emerge in the future.

PMID- 18637533
TI  - Evaluation of immunization knowledge, practices, and service-delivery in the
      private sector in Cambodia.
AB  - A study of private-sector immunization services was undertaken to assess scope of
      practice and quality of care and to identify opportunities for the development of
      models of collaboration between the public and the private health sector. A
      questionnaire survey was conducted with health providers at 127 private
      facilities; clinical practices were directly observed; and a policy forum was
      held for government representatives, private healthcare providers, and
      international partners. In terms of prevalence of private-sector provision of
      immunization services, 93% of the private inpatient clinics surveyed provided
      immunization services. The private sector demonstrated a lack of quality of care
      and management in terms of health workers' knowledge of immunization schedules,
      waste and vaccine management practices, and exchange of health information with
      the public sector. Policy and operational guidelines are required for private
      sector immunization practices that address critical subject areas, such as
      setting of standards, capacity-building, public-sector monitoring, and exchange
      of health information between the public and the private sector. Such
      public/private collaborations will keep pace with the trends towards the
      development of private-sector provision of health services in developing
      countries.

PMID- 18637534
TI  - Does age affect the response to zinc therapy for diarrhoea in Bangladeshi
      infants?
AB  - The benefit of zinc for the treatment of diarrhoea in a cluster-randomized trial
      of children, aged 3-59 months, living in rural Bangladesh was previously
      reported. Here, the benefits of zinc stratified by age--3-5 months, 6-11 months,
      and 12-59 months--are reported. Although the sample sizes in the stratified
      groups were too small to detect statistical significance in the 3-5-month and 6
      11-month age-groups, the trends suggest that there may be a benefit of zinc for
      the treatment of diarrhoea on the duration of diarrhoea and on subsequent
      morbidity and mortality. Additional research is needed to better understand the
      effect of zinc for the treatment of diarrhoea among infants aged less than six
      months.

PMID- 18637535
TI  - Postnatal care of newborns and mothers in developing countries.

PMID- 18637536
TI  - Rickets: an overview and future directions, with special reference to Bangladesh.
      A summary of the Rickets Convergence Group meeting, Dhaka, 26-27 January 2006.
AB  - Rickets has emerged as a public-health problem in Bangladesh during the past two
      decades, with up to 8% of children clinically affected in some areas.
      Insufficiency of dietary calcium is thought to be the underlying cause, and
      treatment with calcium (350-1,000 mg elemental calcium daily) is curative.
      Despite this apparently simple treatment, little is known about the most
      appropriate management of bone deformities of affected children, and further
      studies are needed to determine the details of dosing and duration of calcium
      therapy, the role of bracing, and specific indications for surgical intervention.
      Effective preventive measures that can feasibly reach entire communities are
      needed, and these may differ between various affected regions.

PMID- 18637537
TI  - Not-for-profit hospitals: still a community value.

PMID- 18637538
TI  - James Carville and Mary Matalin make your voices heard in Washington.

PMID- 18637539
TI  - On fiscal wake-up tours and toothless tigers.

PMID- 18637540
TI  - Putting meaning into healthcare reform.

PMID- 18637541
TI  - Working with health information management for revenue cycle improvement.

PMID- 18637542
TI  - A consumer revolution in retail medicine: where is it heading?
AB  - Convenient medical clinics (CMCs) have established themselves as a viable site
      for healthcare services. CMCs continue to gain support because the American
      consumer is driving this retail medicine bus and investment dollars are
      plentiful. Whether CMCs will last appears to depend on whether they continue to
      offer convenient services that meet the needs of those driving the bus.

PMID- 18637543
TI  - Best practices for self-pay collections.
AB  - Hospitals can improve their ability to collect on patient accounts by tailoring
      collection efforts to four segments of patients: Segment A: Patients with a high
      likelihood of payment and low account balances; Segment B: Patients who have high
      original balances, but also a high likelihood of payment; Segment C: Patients who
      have large balances and low expected collection rates; Segment D: Patients with
      low balances and low expected collection rates.

PMID- 18637544
TI  - The right moves for success with Medicare.
AB  - Hospitals can take these steps to meet payment reform challenges: Analyze the
      financial impact of payment changes. Benchmark performance against peers. Audit
      and educate physicians. Implement a concurrent documentation program. Focus on
      length of stay. Get ready for RACs. Take charge of charge capture. Prevent coding
      duplication. Conduct a pricing review. Validate payment reconciliation processes.

PMID- 18637545
TI  - Medicare bad debts are you losing money?
AB  - Providers should adopt strategies to make sure that both their claimed and not
      yet claimed Medicare bad debts will be reimbursed. For periods going forward,
      providers that are not protected by the bad debt moratorium should make sure they
      have a bad debt policy in place that complies with CMS's current policies.

PMID- 18637546
TI  - MIP on the radar: the new drive to end Medicaid fraud.
AB  - To ensure their billing integrity, providers should: Review every aspect of their
      billing integrity compliance program; Review the existing quality and methods of
      their statistical sampling; Examine an agency's or prosecutor's findings of loss
      to ensure accurate loss calculation.

PMID- 18637547
TI  - Rural hospitals: are you missing out on drug savings?
AB  - The 340B Drug Pricing Program requires drug manufacturers to offer outpatient
      drugs at a reduced price to certain safety net organizations that provide
      healthcare services to vulnerable populations. In a survey, participants reported
      pharmacy savings ranging from $600 to $158,000 per month, with a mean savings of
      $19,700 and a median savings of $10,000. The biggest challenge in administering
      the program is maintaining separate records for inpatient and outpatient drugs,
      according to participants.

PMID- 18637548
TI  - RAC'em up: are you prepared for the national recovery audit program?
AB  - CMS's changes to the recovery audit contractor (RAC) program may not be
      sufficient to resolve lingering concerns. With the national RAC program looming,
      providers should be alert to the challenges the program poses and start
      developing a strategy to address them. Filing appeals to challenge RAC
      determinations can be a lengthy process, requiring a substantial amount of
      organization and determination.

PMID- 18637549
TI  - Super CFO: hospital financial leaders soar to new leadership heights.
AB  - Today's healthcare CFO has become a strategic driver of his or her organization.
      A key focus for today's CFO is on treasury and debt management, and he or she is
      likely to have much greater interaction with the hospital board than CFOs did in
      the past. Among the factors that have pushed the CFO to the forefront are the
      changing healthcare reimbursement system, the emergence of hospital systems, and
      improvements in technology.

PMID- 18637550
TI  - Patient registration quality assurance tools.

PMID- 18637551
TI  - How to partner with physicians for higher growth and quality.

PMID- 18637552
TI  - What would you do? Is this system's smaller hospital a keeper?

PMID- 18637553
TI  - New techniques needed to manage accuracy of MS-DRGs.

PMID- 18637554
TI  - Morphological analysis of the connective tissue reaction in linear hypertrophic
      scars treated with intralesional steroid or silicone-gel sheeting. A light and
      electron microscopic study.
AB  - The linear hypertrophic scar has become the most common type of pathologic
      scarring. Silicone-gel sheeting is the first line therapy while intralesional
      steroid is the second. A light and electron microscopic analysis was carried out
      to reveal differences in tissue reaction following the two different treatments.
      Two groups of 12 patients each were treated for 4 months. For the first group,
      diluted Triamcinolone acetonide was injected until an inactive state was
      achieved. The other group of patients was treated with silicone-gel sheeting. The
      scars were examined every two weeks and their appearance documented. After
      reaching the expected therapeutic response, inactive scars were removed. The
      excised scars were evaluated through light microscopic histopathology and
      electron microscopy. The light and electron microscopic observations revealed
      marked differences following treatments. The activity of fibroblasts and the
      numbers of collagen fibers forming bundles decreased and the orientation of the
      collagen fibers was more variable in the treated scars. The amount of elastic
      fibers increased after both steroid and silicone-gel sheeting treatment.
      Vascularization was also slightly changed, with more capillaries and fewer pre
      capillary arteries detected in the treated scars. Both treatments resulted in the
      same decrease in score but steroid treatment was more rapid in onset. We suggest
      that the two different treatments work through different mechanisms, although the
      final functional outcome is similar.

PMID- 18637555
TI  - Postnatal expression of Doublecortin (Dcx) in the developing cerebellar cortex of
      mouse.
AB  - We have investigated the expression of Doublecortin (Dcx) protein in the
      developing cerebellum of mouse from postnatal 2nd day to postnatal 22nd day and
      in young adults by immunohistochemistry. Strong expression of Dcx was present in
      the inner zone of the external granule cell layer, and remained strong while
      postmitotic granule cell precursors were present in this transitory layer.
      Descending granule cell precursors exhibited Dcx immunostaining not only while
      migrating but for a short time also after their settlement. Dcx-immunostained
      cells appeared in deep cerebellocortical territories and in the cerebellar white
      matter during the first postnatal week. These bipolar cells were arranged in the
      sagittal plane and built up transitory migratory streams during the second
      postnatal week and their number gradually decreased during the third postnatal
      week. Upward migration of bipolar cells was observed while leaving the migratory
      streams, penetrating the internal granule cell layer and the molecular layer.
      These cells were considered as precursors of late migrating molecular layer
      interneurons. However, a proportion of Dcx-immunostained cells underwent a
      bipolar-to-multipolar dendritic remodellation and - on the basis of strong
      morphological similarities - was taken for "multipotent progenitor cells",
      described recently in the neocortex of adult rat.

PMID- 18637556
TI  - The effect of pinealectomy on plasma vasopressin response to isotonic, hypertonic
      and hypovolemic treatments in rats supplemented with L-thyroxine.
AB  - The present study was conducted to determine the effects of basal, isotonic as
      well as hypertonic and hypovolemic treatments on fluid-electrolyte balance and
      plasma AVP levels in rats supplemented with L-thyroxine and pinealectomized L
      thyroxine. The animals were initially separated into 4 groups: control (n = 24),
      L-thyroxine treated (n = 24); L-thyroxine + sham-pinealectomy (n = 24) treated
      and 4-L-thyroxine + pinealectomy (n = 24) treated. L-thyroxine was given for 4
      weeks. At the end of the 4-week experimental period, the sub-groups were formed
      before decapitation, which were classified as unstimulated (n = 6), isotonic (n =
      6), hypertonic (n = 6) and hypovolemic (n = 6) stimulation. Plasma AVP, total
      triiodothyronine (TT3) and total thyroxine (TT4) levels were examined in plasma
      by RIA. Hematocrit and osmolality levels were also determined. It was found that
      the TT3 and TT4 levels showed significant increases in L-thyroxine treated groups
      (P <0.001). Also, plasma AVP levels increased in the group subjected to L
      thyroxine treatment. However, this increase was depicted to be significantly more
      prominent in L-thyroxine + pinealectomy treated group (P <0.001). The results of
      the present study indicate that L-thyroxine treatment increases the basal and
      stimulated AVP release, which became more significant in the pinealectomy plus L
      thyroxine treatment group. Moreover, the results indicate that AVP response to
      hypertonic and hypovolemic stimulations does not undergo any change due to
      supplementation by L-thyroxine treatment and/or pinealectomy plus L-thyroxine.

PMID- 18637557
TI  - The effects of ACTH, phytoestrogens and estrogens on corticosterone secretion by
      gander adrenocortical cells in breeding and nonbreeding seasons.
AB  - The aim of this study was to investigate the effects of ACTH, phytoestrogens
      (genistein, daidzein, biochanin A and coumestrol), and animal estrogens
      (estradiol and estrone) on corticosterone secretion by isolated adrenocortical
      cells of the ganders in breeding (April) and nonbreeding seasons (July). ACTH
      stimulated corticosterone output in the breeding season. In July
      (photorefractoriness and postbreeding molt) ACTH had no effect on corticosterone
      production. Coumestrol reduced corticosterone secretion by the cells obtained in
      nonbreeding season. Other examined phytoestrogens did not affect corticosterone
      production. Estrogens showed differentiated effects. Estradiol stimulated the
      corticosterone output in breeding season; estrone inhibited corticosterone
      release in July. The season can probably affect sensitivity of isolated gander
      adrenal cells, especially to ACTH. It seems that goose adrenocortical cells, in
      contrast to the mammalian cells, can be weakly sensitive to phytoestrogens.

PMID- 18637558
TI  - Liver and heart mitochondria obtained from Adelie penguin (Pygoscelis adeliae)
      offers high resistance to lipid peroxidation.
AB  - Lipid peroxidation is generally thought to be a major mechanism of cell injury in
      aerobic organisms subjected to oxidative stress. All cellular membranes are
      especially vulnerable to oxidation due to their high concentration of
      polyunsaturated fatty acids. However, birds have special adaptations for
      preventing membrane damage caused by reactive oxygen species. This study examines
      fatty acid profiles and susceptibility to lipid peroxidation in liver and heart
      mitochondria obtained from Adelie penguin (Pygoscelis adeliae). The saturated
      fatty acids in these organelles represent approximately 40-50% of total fatty
      acids whereas the polyunsaturated fatty acid composition was highly distinctive,
      characterized by almost equal amounts of 18:2 n-6; 20:4 n-6 and 22:6 n-3 in liver
      mitochondria, and a higher proportion of 18:2 n-6 compared to 20:4 n-6 and 22:6 n
      3 in heart mitochondria. The concentration of total unsaturated fatty acids of
      liver and heart mitochondria was approximately 50% and 60%, respectively, with a
      prevalence of oleic acid C18:1 n9. The rate C20:4 n6/C18:2 n6 and the
      unsaturation index was similar in liver and heart mitochondria; 104.33 +/- 6.73
      and 100.09 +/- 3.07, respectively. Light emission originating from these
      organelles showed no statistically significant differences and the
      polyunsaturated fatty acid profiles did not change during the lipid peroxidation
      process.

PMID- 18637559
TI  - Analysis of the applicability of molecular markers linked to the PVY extreme
      resistance gene Rysto, and the identification of new markers.
AB  - In this study molecular markers linked to the Rysto gene, which originates from
      the wild potato species Solanum stoloniferum and confers extreme resistance
      against PVY, were identified and the applicability of recently published Rysto,
      markers was analyzed. Three RAPD markers covering a total distance of 8.60 cM
      were detected in this experiment. The closest of these markers was located 0.53
      cM from the gene. From among the published markers only one had diagnostic value
      in the experimental plant material, and mapped 2.95 cM from the gene, on the side
      opposite the RAPD markers developed in the present study. All the markers
      analyzed were present in Solanum stoloniferum accessions, irrespective of their
      resistance, indicating that these sequences are linked to the locus and not
      exclusively to the dominant allele of the Rysto gene in the wild species. The
      inapplicability of several published markers indicates that the genetic
      background is decisive in this tetraploid and highly heterozygous species. This
      means that it may be necessary to develop markers from the breeding material
      itself, until the resistance gene is not cloned and cannot be used as a selection
      marker in marker-assisted selection.

PMID- 18637560
TI  - Effects of temperature and light intensity on flowering of barley (Hordeum
      vulgare L.).
AB  - In order to analyse the effects of temperature (9-22 degreesC) and light
      intensity (170-576 micromol m(-2) s(-1)) on plant development two barley
      varieties with contrasting seasonal growth habits were included in a series of
      experiments consisting of controlled environment tests. The effect of constant
      (18 degrees C) and daily fluctuating (18/16 degrees C) temperature with a long
      photoperiod was also examined in a set of barley varieties including winter,
      facultative and spring barleys. Dicktoo with facultative growth habit was more
      sensitive to unfavourable conditions than Kompolti korai with winter growth
      habit; the flowering of Dicktoo was significantly delayed by sub- and supra
      optimal temperatures and low light intensity accompanied by higher or fluctuating
      temperatures. The optimal temperature at flowering was also significantly lower
      for Dicktoo than for Kompolti korai (16.0 degrees C vs. 21.0 degrees C,
      respectively). Plant development was the fastest when there was no fluctuating
      environmental factor in the growing conditions and was significantly delayed with
      application of photo cycle. The addition of thermo cycle to photo cycle had an
      even stronger delaying effect. Facultative barleys were the most sensitive,
      followed by winter barleys, while spring barleys the least sensitive to the
      introduction of thermo cycle.

PMID- 18637561
TI  - Efficiency of the photosynthetic apparatus in developing needles of Norway spruce
      (Picea abies L. Karst.).
AB  - The photosynthetic performance of developing spruce (Picea abies L. Karst.)
      needles was investigated. As revealed by previous reports, the biosynthesis of
      chlorophylls and carotenoids was not following the characteristic chloroplast
      ultrastructure building up during needle elongation process. The aim of our study
      was to investigate photosynthetic capability (evaluated by oxygen evolution and
      chlorophyll a fluorescence kinetics measurements), the dynamics of chloroplast
      pigments biosynthesis and the expression of major photosynthetic proteins as well
      as to find out possible correlation between components of issue. Low amounts of
      chlorophylls and carotenoids, LHC II and Rubisco LSU were detected in the
      embryonic shoot of vegetative buds. Although PS II was functional, oxygen
      production was not sufficient to compensate for respiration in the same
      developmental stage. The light compensation point of respiration was successively
      lowered during the needle elongation. Nevertheless the significant increase in
      photosynthetic pigments as well as the high level of expression of LHC II and
      Rubisco LSU proteins was observed in the later stages of needle development. Our
      results suggest that, besides light, some other environmental factors could be
      critical for producing fully functional chloroplasts in rapidly growing young
      needles.

PMID- 18637562
TI  - Effect of copper excess on H2O2 accumulation and peroxidase activities in bean
      roots.
AB  - We studied oxidative stress and peroxidase activity resulting from application of
      excess copper in the nutrient medium on the roots of young bean seedlings. The
      change in H2O2 content, lipid peroxidation and antioxidant enzymes activities
      were quantified and located. Excess of copper caused a loss of membrane integrity
      and the formation of hydrogen peroxide (H2O2) as visualized in the transmission
      electron microscopy and measured using spectrophotometry. H2O2 accumulated in the
      intercellular spaces and in the cell wall. The production of H2O2 was accompanied
      by an increase in the activity of soluble and ionic GPX (guaiacol peroxidase, EC
      1.11.17), CAPX (coniferyl alcohol peroxidase) and NADH oxidase.

PMID- 18637563
TI  - Response of growth and antioxidant enzymes in Azolla plants (Azolla pinnata and
      Azolla filiculoides) exposed to UV-B.
AB  - Effect of ultravilolet-B (0.4 Wm(-2)) irradiation on growth, flavonoid content,
      lipid peroxidation, proline accumulation and activities of superoxide dismutase
      and peroxidase was comparatively analysed in Azolla pinnata and Azolla
      filiculoides. Growth measured as increment in dry weight reduced considerably due
      to all UV-B treatments. However, the reduction was found to be severe in A.
      filiculoides as compared to A. pinnata. The level of UV-absorbing compound
      flavonoids increased significantly in A. pinnata plants whereas only a slight
      increase in the flavonoid content was observed in A. filiculoides. UV-B exposure
      led to enhanced production of malondialdehyde (MDA) and electrolyte leakage in A.
      filiculoides than A. pinnata. Proline accumulation also showed a similar trend.
      Marked differences in the activity of antioxidant enzymes such as superoxide
      dismutase (SOD) and peroxidase (POD) was noticed in both the plants exposed to UV
      B. Our comparative studies indicate A. pinnata to be better tolerant to UV-B as
      compared with A. filiculoides which appears to be sensitive.

PMID- 18637564
TI  - Purification and preliminary characterization of a cold-adapted extracellular
      proteinase from Trichoderma atroviride.
AB  - Eleven cold-tolerant Trichoderma isolates were screened for the production of
      proteolytic activities at 10 degrees C. Based on the activity profiles determined
      with paranitroanilide substrates at 5 degrees C, strain T221 identified as
      Trichoderma atroviride was selected for further investigations. The culture broth
      of the strain grown at 10 degrees C in casein-containing culture medium was
      concentrated by lyophilization and subjected to gel filtration, which was
      followed by chromatofocusing of the fraction showing the highest activity on N
      benzoyl-Phe-Val-Arg-paranitroanilide. The purified enzyme had a molecular weight
      of 24 kDa, an isoelectric point of 7.3 and a pH optimum of 6.2. The temperature
      optimum of 25 degrees C and the low thermal stability suggested that it is a true
      cold-adapted enzyme. Substrate specificity data indicate that the enzyme is a
      proteinase with a preference for Arg or Lys at the P1 position. The effect of
      proteinase inhibitors suggests that the enzyme has a binding pocket similar to
      the one present in trypsin.

PMID- 18637565
TI  - Basiliximab vs. limited-dose daclizumab (2 mg/kg) administered in single or two
      separated doses in kidney transplantation.
AB  - INTRODUCTION: Addition of anti-IL2r monoclonal antibodies (chimeric or humanized)
      for induction therapy has reduced the frequency of acute rejection (AR). This
      study compares the impact of type and dosage of induction therapy on frequency of
      acute rejection and on renal function during the first year post-transplant.
      PATIENTS AND METHODS: Comparative retrospective study. Kidney transplant
      recipients (KTR) were divided in three groups according to induction therapy, as
      follows: (1) Basiliximab in two 20 mg doses, (2) Daclizumab 2 mg/kg in one dose,
      and (3) Daclizumab 2 mg/kg divided in two doses (1 mg/kg each). Groups were
      paired for age, sex, number of shared haplotypes, and previous transplant
      history. Primary endpoints were AR episodes, time to first AR, graft loss, and
      death. Secondary endpoints were SCr (at 3, 6, 9 and 12 months), frequency and
      type of infection, and cost. RESULTS: There were no baseline differences between
      groups. Twenty one patients were included in each group. The incidence of AR was
      similar: 14.2% in group 1, and 9.5% for groups 2 and 3. Two deaths were reported,
      one in group 1 and another in group 2. Mean SCr was similar between groups.
      Incidence of infection was 6, 5, and 7 in groups 1 to 3, respectively without a
      significant difference. The cost was higher in group 1 (p < 0.001). CONCLUSION:
      Low dose Daclizumab in one or two doses is equally effective and safe as
      basiliximab at 12-month follow-up, with inferior cost.

PMID- 18637566
TI  - [Frequency of focal prostatic carcinoma and atypical glandular proliferations in
      1,000 needle prostatic biopsies].
AB  - INTRODUCTION: With the routine use of prostatic specific antigen blood
      determination, sextant biopsies and immunohistochemical studies, focal carcinomas
      and atypical glandular proliferations (AGP), limited to isolated histologic
      fields are being detected more frequently. The recognition of these lesions is
      important since many of them correspond to potentially curable cancers or to
      benign lesions that mimic carcinoma. MATERIAL AND METHODS: 1,000 consecutive
      prostatic biopsies performed during the period of 2000-2007 were reviewed. 42
      focal prostatic lesions were retrieved. We reassessed the original HE slides.
      Additional histologic sections and immunohistochemical studies were performed in
      those cases with uncertain diagnoses in order to clarify the nature of the
      lesions. RESULTS: Thirteen (1.3%) lesions corresponded to focal carcinomas and 29
      (2.9%) to AGP. Immunohistochemical studies and the analysis of additional
      histologic sections allowed the classification of 17 cases of AGP into specific
      categories (prostatic adenosis, atrophy, atypical basal cell hyperplasia and
      seminiferous ducts). Only three of the 13 patients diagnosed with focal
      carcinomas were subjected to radical prostatectomy in our institution; all of
      them had disease limited to the prostatic gland. Of the 29 AGP, additional
      biopsies were taken in four cases and in one of them prostatic carcinoma was the
      final diagnosis. CONCLUSIONS: A significant number of AGP biopsies could be sub
      classified in to specific diagnostic categories with the use of
      immunohistochemical studies and additional HE levels. The frequency of focal
      carcinoma and AGP in our material was similar to other series; however in many of
      the AGP cases additional biopsies were not performed despite its high predictive
      value for carcinoma. Increase use of follow-up biopsy procedures is needed in
      order to detect early potentially curable lesions.

PMID- 18637567
TI  - [Neonatal and maternal morbidity among adolescent and adult women. A comparative
      study].
AB  - OBJECTIVE: To identify neonatal and maternal morbidity among adolescent and adult
      women. MATERIAL AND METHODS: We used a cross sectional study design. Recorded
      data from newborn infants: gestational age, birth weight, sex, route of delivery,
      Apgar score, Silverman score and morbidity; and mothers' data reviewed: age,
      marital status, scholarship, occupation, monthly income, drug abuse history,
      number of pregnancies, abortion, deliveries, cesarean section, prenatal follow up
      and complications during the pregnancy. RESULTS: One hundred newborn infants were
      studied in each group. Complications during pregnancy were present among 26% of
      adult women and 10% of adolescents (p = 0.04). Gestational age and birth-weight
      were similar in both groups. Birth by cesarean section was more frequent among
      the offspring of adult women (65% vs. 48%, p = 0.015). Perinatal asphyxia and
      birth trauma were observed more often in children from adolescent mothers (p <
      0.05). Mortality rate was 5% and 1% among the offspring of adolescent and adult
      women, respectively. CONCLUSIONS: The morbidity in pregnancy was more frequent in
      adult women. The offspring of adolescent women had a higher incidence of
      perinatal complications like asphyxia and birth trauma. Mortality rate was higher
      in children from adolescent mothers.

PMID- 18637568
TI  - Preclinical evaluation of the therapeutic effect of adenoviral vectors in human
      papillomavirus-dependent neoplasias.
AB  - Gene therapy with adenoviral vectors can eliminate neoplasic cells through
      selective replication and/or through pro-apoptotic, immunogenic or suicide gene
      expression. However, an adenoviral vector may provide anti-cancerous effects even
      in the absence of replication or therapeutic gene expression. The present study
      evaluates the therapeutic effects caused by the administration of an adenoviral
      vector, alone, in HPV-dependent neoplasias (HPV-N). In vivo trials were carried
      out in two HPV-N mouse models. One model was immunocompetent and the other was
      immunodeficient. In both models, the effect of intratumoral administration of
      saline solution (PBS) was compared with administration of an adenoviral vector
      that had no replicative capacity or therapeutic gene (Ad-BGal). In the
      immunocompetent mice, Ad-BGal adenoviral vector administration significantly
      reduced tumor growth, compared with PBS. No differences were observed in the
      immunodeficient mice. In conclusion, the present study lends support to the use
      of adenoviral vectors in HPV-N treatment since they are capable of generating an
      antitumoral effect in immunocompetent individuals, even in the absence of a
      therapeutic gene or viral vector replication.

PMID- 18637569
TI  - [Diabetes, pregnancy and birth defects].
AB  - BACKGROUND: Diabetes mellitus affects 3 to 10% of pregnant women. The reported
      frequency of congenital malformations (CM) in diabetic mothers is 5.5 to 10%,
      contributing these defects to approximately 40% of the neonatal mortality in
      children of diabetic mothers (CDM). OBJECTIVE: To investigate the frequency and
      type of congenital malformations in a sample of livebirths of diabetic mothers
      from the Mexican population. MATERIAL AND METHODS: The analyzed information was
      obtained from the RYVEMCE (Registro y Vigilancia Epidemiologica de Malformaciones
      Congenitas). We analysed the type and frequency of the different CM diagnosed.
      These frequencies were compared with the whole amount of those CM included in the
      database of our registry (20,381). As part of the analysis, other maternal and
      neonatal variables were also compared between CDM and the control group. RESULTS:
      A total of 314 CDM (0.77%), 234 malformed and 80 non malformed were identified.
      The frequencies of cleft palate (CP), limb reduction defect (LRD) and
      microcephaly (MIC) were significantly higher in CDM than in the rest of malformed
      newborns of not diabetic mothers of the RYVEMCE (OR: 9.9, 3.8 and 10.0,
      respectively). A higher frequency of macrosomia was observed in CDM (18.0%) than
      in controls (6.1%), OR: 3.4, p < 0.001, in the frequency of preterm birth (28.5%
      than controls 13.0%), OR: 3.02, p < 0.0001 and in caesarean delivery (71.5% than
      controls 44.4%) OR: 3.15, p < 0.00001. CONCLUSIONS: Our results confirm the
      higher frequency of CM in CDM and in particular a higher risk for CP, LRD and
      MIC. Pregnancy and delivery complications such as macrosomia and preterm and
      caesarean delivery were also more frequent in CDM that controls. Certain
      associations of CM not described previously, were observed in the studied sample.
      Our results confirm the need of pregnancy planning including a pre-gestational
      and gestational control of maternal glycaemia, particularly in a population with
      such a high prevalence of diabetes mellitus as the observed in the Mexican one.

PMID- 18637570
TI  - [Pre-eclampsia, eclampsia: clinical aptitude on primary attention].
AB  - OBJECTIVE: To compare the clinical aptitude in preeclampsy and eclampsy attention
      in medical personnel that work in first level of attention. MATERIALS AND
      METHODS: A cross-sectional, prospective comparative study was performed to
      compare the clinical aptitude in pre-eclampsy and eclampsy attention in family
      practice physicians. A questionnaire comprising four clinical real cases, that
      belong to maternal death cases developed in the previous year of the study, was
      applied to 77 doctors that work at a familiar medicine unit. This questionnaire
      was formed by 109 statements, 54 were true correct answers and 55 were false
      correct answers. To compare the clinical aptitude among the group of physicians
      evaluated, a Kruskal-Wallis and U Mann-Whitney tests were used. RESULTS: In
      general any difference were observed in the clinical aptitude in pre-eclampsy and
      eclampsy according to the obtained academic degree and the antiquity at work (p =
      NS). The clinical aptitude level identified was the mean level, with a medium of
      57 to 74 of a theoretical total of 109. CONCLUSIONS: The development grade about
      clinical aptitude that present family practice physicians was not the desirable,
      for the optimal attention in this pathology.

PMID- 18637571
TI  - [Mechanism of regulation of synthesis and secretion of human chorionic
      gonadotropin (hCG) during pregnancy].
AB  - Human chorionic gonadotropin (hCG) is an essential hormone for development and
      sustaining of gestation. Adequate hCG production is fundamental for pregnancy
      success since abnormal hCG serum concentrations have been correlated with
      pregnancy anomalies such as recurrent abortions and preeclampsia. Regulation of
      hCG production involves diverse molecules associated with different signaling
      pathways, which have complicated the establishment of the mechanisms involved in
      its production. The present study provides a critical review of the most relevant
      findings related to hCG production and functions during pregnancy, in order to
      help to understand some related pathologies and to treat them more adequately.

PMID- 18637572
TI  - [The reflective experience and education].
AB  - The reflective experience is proposed in this article as the way to approach the
      elaboration of knowledge. The concept of vital experience is proposed to make
      reference to the links with a great affective significance that characterizes
      each person in his/her relation with the world. Some considerations are made
      about perception with its affective, cognitive and evaluative components and its
      implications in the knowledge process. The idea of knowledge as the use and
      consumption of information is discussed. This idea that prevails at school
      corresponds with the passive perspective of education. We propose the idea of
      knowledge as an elaboration of the person in knowledge situation which originates
      the participative perspective of education. The characteristics of both
      perspectives of education are contrasted with respect to the role of theory and
      practice, the role of the professor and the student, the main purposes and the
      type of society that they aspire. The more relevant aspects of participative
      education are shown: the practice of criticism and self-criticism; the
      development of solid points of view about problem situations of experience, the
      development of methodological and practical aptitudes, with emphasis on medical
      education. Considerations are made about in what way the participative
      perspective concerns pre-graduate and post-graduate medical education and its
      possible incorporation to the programs.

PMID- 18637573
TI  - [Beverage consumption for a healthy life: recommendations for the Mexican
      population].
AB  - The Expert Committee in charge of developing the Beverage Consumption
      Recommendations for the Mexican Population was convened by the Secretary of
      Health for the purpose of developing evidence-based guidelines for consumers,
      health professionals, and government officials. The prevalence of overweight,
      obesity and diabetes have dramatically increased in Mexico; beverages contribute
      a fifth of all calories consumed by Mexicans. Extensive research has found that
      caloric beverages increase the risk of obesity. Taking into consideration
      multiple factors, including the health benefits, risks, and nutritional
      implications associated with beverage consumption, as well as consumption
      patterns in Mexico, the committee classified beverages into six levels.
      Classifications were made based on caloric content, nutritional value, and health
      risks associated with the consumption of each type of beverage and range from the
      healthier (level 1) to least healthy (level 6) options, as follows: Level 1:
      water; Level 2: skim or low fat (1%) milk and sugar free soy beverages; Level 3:
      coffee and tea without sugar; Level 4: non-caloric beverages with artificial
      sweeteners; Level 5: beverages with high caloric content and limited health
      benefits (fruit juices, whole milk, and fruit smoothies with sugar or honey;
      alcoholic and sports drinks), and Level 6: beverages high in sugar and with low
      nutritional value (soft drinks and other beverages with significant amounts of
      added sugar like juices, flavored waters, coffee and tea). The committee
      recommends the consumption of water as a first choice, followed by no or low
      calorie drinks, and skim milk. These beverages should be favored over beverages
      with high caloric value or sweetened beverages, including those containing
      artificial sweeteners. Portion size recommendations are included for each
      beverage category and healthy consumption patterns for men and women are
      illustrated.

PMID- 18637574
TI  - [Three-way translocation t(3;12;21)(q26.2;q24.1;q22) in a girl with de novo acute
      megakaryoblastic leukemia].

PMID- 18637575
TI  - [Maturation of dendritic cells and activation of B-lymphocytes in spleens of ICR
      mice infected with chloroquine-resistant Plasmodium berghei].
AB  - OBJECTIVE: To investigate the relation between activation of B-cells and
      maturation of dendritic cells (DC) in the spleens of ICR mice infected with
      chloroquine-resistant (RC) or chloroquine-sensitive (N) strain of Plasmodium
      berghei. METHODS: Spleens were taken after the mice were infected with N or RC
      strains of P. berghei and attained certain degree of parasitemia. Changes of B
      cells and DCs were examined by pathological method, immunohistochemistry and
      immunofluorescence methods, transmission electron microscopy (TEM) and flow
      cytometry technology. RESULTS: Proliferation of white pulps in the spleen of mice
      infected with RC strain was found as compared to that with N strain. The
      percentage of cluster of differentiation (CD) 45R/B220, CD19 cells increased in
      the spleen cells, number of medium and small lymphocytes increased in the
      germinal centers, the immature and mature plasma cells also increased in the red
      pulps of spleen in RC strain-infected mice. On the contrary, in the N strain
      infected mice spleen, the white pulps were reduced and the red pulps were filled
      with parasite-infected red blood cells; less small lymphocytes, immature and
      mature plasma cells were observed in red pulps. The number of CD11c DCs
      increased, especially in the periarteriolar lymphoid sheath, T cell area; the
      expression of major histocompatibility complex II (MHC II) on DC was up-regulated
      in RC strain-infected mice as compared to that in N strain-infected mice. TEM
      showed that the DCs in RC strain-infected mice spleens were more active than that
      in N strain-infected mice. CONCLUSION: Infection of RC strain P. berghei
      increases mature DCs in the spleen, which induces the proliferation of B cells
      and immune response.

PMID- 18637577
TI  - [Effect of paeoniflorin on hepatic immunopathogenesis in mice with Schistosoma
      japonicum infection].
AB  - OBJECTIVE: To investigate the mechanism of paeoniflorin in preventing hepatic
      granuloma formation and fibrosis in mice infected with Schistosoma japonicum.
      METHODS: Model of hepatic granuloma and fibrosis was established by infecting
      mice with S. japonicum cercariae. The infected mice were randomly divided into 4
      groups: group A as model (infected control) group (15 mice), and paeoniflorin
      being given before, simultaneously and after praziquantel treatment as groups B,
      C and D. Each of the groups B, C and D was subdivided into 3 subgroups (15 mice
      each): low dose (paeoniflorin 2 ml, 30 mg/(kg x d) x 30 d), high
      dose(paeoniflorin 2 ml, 120 mg/(kg x d) x 30 d) and control (2 ml, 0.5% sodium
      carboxymethylcellulose x 30 d). In group B, paeoniflorin or sodium
      carboxymethylcellulose was orally administrated on 12 d after infection. In
      groups C and D, paeoniflorin or sodium carboxymethylcellulose was administrated
      on 42 d or 72 d after infection. Each of group B, C and D was orally given
      praziquantel 2 ml (500 mg/(kg x d) x 2 d) on 42 d after infection. On the 102nd
      day after infection, all animals were sacrificed by cervical dislocation. Serum
      hyaluronic acid (HA) was detected by radioimmunoassay; area of egg granuloma and
      degree of hepatic fibrosis were observed via HE and Masson stainings; the
      expression of transforming growth factor beta1 (TGF-beta1), alpha smooth muscle
      actin (alpha-SMA and collagen I (Col I) protein were measured by
      immunohistochemical method. RESULTS: In group B, the level of HA (0.719 +/- 0.239
      microg/ml, 0.721 +/- 0.182 microg/ml) in low or high dose subgroups was
      significantly lower (F = 9.429, P < 0.01) than the control subgroup (1.049 +/-
      0.286 microg/ml); the area of granuloma (0.066 +/- 0.005 mm2, 0.064 +/- 0.004
      mm2) or the degree of hepatic fibrosis (2.067 +/- 0.458, 1.967 +/- 0.399) in low
      or high dose subgroups was significantly greater (F = 862.540, F = 29.738, P <
      0.01) than the control (0.141 +/- 0.008 mm2, 3.467 +/- 0.834); the expression of
      alpha-SMA positive cells (2.933 +/- 0.594, 3.000 +/- 0.535) in low or high dose
      subgroups was significantly lower (F = 12.323, P < 0.01, P < 0.01) than its
      control (4.800 +/- 1.859); the expression of TGF-beta1 (0.256 +/- 0.057, 0.274 +/
      0.054) in low or high dose subgroups was significantly lower (F = 148.990, P <
      0.01) than its control (0.552 +/- 0.047); the content of Col I (0.334 +/- 0.041,
      0.339 +/- 0.042) in low or high dose subgroups was significantly lower (F =
      180.881, P < 0.01) than its control (0.601 +/- 0.049). In groups C & D, no
      significant difference was found between the low or high dose subgroups or
      between the subgroups and their corresponding controls. CONCLUSION: Paeoniflorin
      can significantly reduce hepatic granuloma formation and fibrosis due to
      schistosome eggs, and decrease the expression of TGF-beta1, alpha-SMA in mice
      when it is given before praziquantel administration, which may associate with the
      activation of hepatic stellate cells and the expression of TGF-beta1 in liver
      tissue.

PMID- 18637576
TI  - [Tribendimidine enteric coated tablet in treatment of 1,292 cases with intestinal
      nematode infection--a phase IV clinical trial].
AB  - OBJECTIVE: To further evaluate the efficacy and safety of tribendimidine in
      treatment of adult patients with intestinal nematode infections. METHODS: An open
      and multi-center clinical trial was conducted in the provinces of Hainan, Sichuan
      and Guizhou. A total of 1,292 infected cases aged 15-70 years were enrolled in
      the study. Modified Kato-Katz method was used to diagnose the cases with
      intestinal nematode infections and assess the efficacy 3-4 weeks post treatment.
      Patients with Ascaris lumbricoides infection were treated orally with
      tribendimidine enteric coated tablets at a single dose of 300 mg, while in the
      patients with Ancylostoma duodenale, mixed A. duodenale and A. lumbricoides, or
      with other helminth infections, a single dose of 400 mg was administered.
      RESULTS: The cure rate and effective rate of the patients with Ancylostoma
      infection were 88.4% (1,009/1,141) and 99.1% (1,131/1,141), respectively, while
      in patients with A. lumbricoides infection, they were 95.0% (419/441) and 99.8%
      (440/441), respectively. The cure rate of tribendimidine enteric coated tablet
      given to patients with Trichuris trichiura infection at a single dose of 400 mg
      was 76.8% (109/142). The adverse effect induced by tribendimidine was light and
      transient with a rate of 3.3% (42/1,292). No apparent impact was seen on blood
      and urine routine examinations, hepatic and renal functions as well as ECG
      examination. CONCLUSION: It is further confirmed that under the used dosage for
      expanding treatment in larger sample of patients with various ages and infected
      with Ancylostoma duodenale, A. lumbricoides and other helminths, tribendimidine
      enteric coated tablet is safe with satisfactory efficacy.

PMID- 18637578
TI  - [Schistosomiasis transmission in areas where inhabitants migrated from outside
      embankment to new settlement].
AB  - OBJECTIVE: To observe the impact on the transmission of schistosomiasis in areas
      where the local inhabitants migrated from outside embankment to new settlements.
      METHODS: Two villages (Chenqiao and Qingjie) where the inhabitants had moved out
      and another 2 villages (Jiangzhou and Xiaohuang) disused for both inhabitants and
      cultivated land were selected for the investigation. Data on prevalence in human
      and domestic animals, and Oncomelania snail habitats, were collected. RESULTS:
      After moving from outside embankment to new settlements, the density of infested
      snails in Chenqiao and Qingjie decreased by 79.1% and 45.2% in 2005 compared with
      that in 2002, and the infection rate of snails decreased by 75.5% and 84.9%,
      respectively (P < 001). In Jiangzhou and Xiauhuang, the density of infested
      snails decreased by 100% and 74.9% in 2005 compared with that in 2002, and the
      infection rate of snails decreased by 100% and 40.0%, respectively (P > 0.05). In
      villages that only disused for inhabitants, the density and egg-positive rate of
      feces collected from the wild were higher than the other 2 villages. However, in
      villages disused for both inhabitants and cultivated land, the density and egg
      positive rate of wild feces decreased gradually and no egg-positive feces was
      found in 2005. The prevalence of schistosomiasis in humans in villages disused
      only for inhabitants changed slightly from 2002 to 2005, but decreased gradually
      in villages disused for both inhabitants and cultivated land. Higher prevalence
      in cattle was found in villages disused only for inhabitants. Number of cattle
      reduced yearly and no cattle left in villages disused for both inhabitants and
      cultivated land in 2005. CONCLUSION: No significant change on the factors of
      schistosomiasis transmission has been found in villages disused only for
      inhabitants, but the transmission has been effectively controlled in villages
      disused for both inhabitants and cultivated land.

PMID- 18637579
TI  - [Cloning, expression and identification of membrane protein Tetraspanin 2-A of
      Schistosoma japonicum].
AB  - OBJECTIVE: To clone and express a membrane protein (Tetraspanin 2) gene of
      Schistosoma japonicum (SjTsp2). METHODS: A pair of primers was designed to
      amplify the SjTsp2 gene which was subcloned into prokaryotic plasmid pET28a(+).
      The recombinant plasmid was transformed into E. coli BL21(D3) and followed by
      expression of the protein induced by IPTG. The protein was purified by affinity
      chromatography and used to immunize BALB/c mice. Dilution of antibody against
      SjTsp2 was determined by ELISA. The protein was also identified by Western
      blotting. RESULTS: Big loop of SjTsp2-A, 228 bp, was amplified in vitro by PCR.
      Its deduced amino sequence shared 52% similarity with SmTsp2. The soluble
      recombinant SjTsp2-A was expressed in the experiment and high dilution antibody
      against the recombinant (1:32,000 in maximum) was produced in immunized mice.
      SjTsp2-A reacted positively with sera of acute and chronic schistosomiasis
      patients but not with sera from healthy persons by Western blotting. CONCLUSION:
      SjTsp2 has been expressed and shows certain antigenicity.

PMID- 18637580
TI  - [Ecological niches of sucking lice (Phthiraptera: Anoplura) and their coevolution
      relationship with small mammal hosts in Yunnan, China].
AB  - OBJECTIVE: To investigate the ecological niches of sucking lice (Phthiraptera:
      Anoplura) on the body surface of small mammal hosts and the co-evolutionary
      relationship between lice and mammal hosts in Yunnan Province. METHOD: Thirty
      species of small mammals were captured and used as 30 resource sequences. The
      distribution and composition of the dominant 22 species of sucking lice on the
      body surface of the 30 species small mammal hosts were analyzed as the
      utilization proportion for each resource sequence. The niche breadth and
      proportional similarity were measured. SPSS 13.0 statistical software was used
      for analyzing the niche overlap matrix of sucking lice by hierarchical clustering
      analysis, and a dendrogram was made. RESULTS: The niche breadth was narrow for
      most species of sucking louse. Among the detected species, Hoplopleura pacifica
      showed the widest niche breadth, but only 0.1536. Indices of niche proportional
      similarity of most sucking lice were relatively small from 0.0005 to 0.4695. The
      22 species of sucking lice were classified into 16 niche overlap groups, by
      lambda = 5.5, through a hierarchical clustering analysis for the niche overlaps,
      and the clustering process of most sucking lice was late. CONCLUSION: The sucking
      lice have a high specificity for hosts, of which different species show an
      apparent niche divergence on host selection. The results reveal a high
      coevolution between sucking lice and the mammal hosts.

PMID- 18637581
TI  - [Putation, identification and bioinformatics analysis of Schistosoma japonicum
      aldehyde dehydrogenase full coding sequence].
AB  - OBJECTIVE: To acquire the full coding sequence of Schistosoma japonicum aldehyde
      dehydrogenase, and fill the gaps of the partial aldehyde dehydrogenase sequences.
      METHOD: Putative sequence fragments of the S. japonicum aldehyde dehydrogenase
      were extracted from the transcriptome database by use of bioinformatics tools,
      through the multiple sequences alignment with homologous sequences of other
      species. Primers were designed according to the EST sequences matching the N
      terminal and C terminal respectively, and the gap sequence fragment was amplified
      by RT-PCR and sequenced. The full gene sequence was obtained finally by combining
      the old 2 EST sequences with the amplified sequence. The physico-chemical
      parameters of the new sequence were analyzed by using bioinformatics software.
      RESULT: Eight EST sequences of S. japonicum were predicted as partial sequences
      of aldehyde dehydrogenase. Two of which (AAW27891, AAW27047) were predicted to
      represent the N terminal and C terminal of one protein, respectively. The gap
      between them was deduced as about 80 amino acids according to the result of
      multiple sequences alignment. Primers located on the flanking of the gap were
      designed according to the known EST sequences of AAW27891 and AAW27047. The gap
      between the AAW27891 and AAW27047 were obtained by RT-PCR and then sequenced, as
      well as confirmed by bioinformatics software. The full sequence of aldehyde
      dehydrogenase was reassembled by filling of the gap sequence. The reassembled
      gene coding sequence was submitted to GenBank with an accession number of
      EF503564. The coding sequence contains an intact ORF of 1,596 bps with deduced
      531 amino acids. Bioinformatic analysis of new amino acids sequence was performed
      as deduced molecular weight of 57 330.7 and PI value of 7.94. The aldehyde
      dehydrogenase pattern of [LIVMFGA]-E-[LIMSTAC]-[GS]-G-[KNLM]-[SADN]-[TAPFV] was
      found located in the position 290-297 of the new sequence. CONCLUSION: The gap
      between two partial nucleotide sequences is filled and the full coding sequence
      of aldehyde dehydrogenase gene has been obtained by the method combining
      bioinformatics tools and experiments together.

PMID- 18637582
TI  - [Effect of IgG3 antibody purified from sera of Microtus fortis against
      Schistosoma japonicum].
AB  - IgG3 antibody reaction to soluble antigens prepared from schistosomula (SSA),
      adult worms (SAWA) and eggs (SEA) in laboratory-bred Microtus fortis (Mf), BALB/c
      mice and Kunming (Km) mice challenged by cercariae of Schistosoma japonicum was
      detected by indirect ELISA. The effect of purified IgG3 antibody on in vitro
      killing schistosomula and protecting mice from infection of S. japonicum was
      evaluated. The IgG3 antibody level in Mf against SSA and SAWA increased
      significantly by 79.6 percent and 49.6 percent after the fourth week of challenge
      infection, but no significant increase in BALB/c mice. Purified IgG3 antibody
      from laboratory-bred Mf and wild Mf effectively killed schistosomula, and that of
      the wild Mf induced higher worm-reduction rate. The death rate of schistosomula
      due to IgG3 antibody purified from sera of laboratory-bred Mf and wild Mf was
      2.35 and 5.88 times as high as that of Km mice respectively. The results suggest
      that IgG3 antibody from Microtus fortis may play an important role in immunity
      against S. japonicum.

PMID- 18637583
TI  - [Sequence polymorphism of major house dust mite allergens].
AB  - OBJECTIVE: To determine the sequence variation of the groups 1 and 2 allergens
      from Dermatophagoides pteronyssinus and Dermatophagoides farinae in different
      geographical regions. METHODS: RNAs were isolated from the whole bodies, eggs and
      entire culture of mites (D. farinae) from South China and European commercialized
      D. pteronyssinus and D. farinae. Sequences of prepeptide, propeptide and mature
      peptide fragments in group 1, and prepeptide and mature peptide fragments in
      group 2 were determined from cDNA produced by PCR. All the sequences were
      compared with the corresponding standards in GenBank. RESULTS: Der p 1.0105 was
      the major variant found in European commercialized Der p 1 clones, where amino
      acid variations appeared sporadic, except for frequent substitutions shown in
      residues 124, 50 and 19, and eight novel homologous variants were identified.
      Derp 2.0104 was mostly detected in clones from European commercialized Der p 2,
      where amino acid substitutions were predominant in residues 40, 47, 111 and 114,
      and six novel homologous variants were identified. Very few amino acid sequence
      substitutions were found among South China based Der f 1 clones, where three
      novel homologous variants were identified. As compared with European
      commercialized ones, a number of homologous variants were recognized unique to
      South China based Der f 2 clones where six novel homologous variants were
      identified. There was no significant difference in major allergens among variants
      from the whole mite bodies, eggs or the entire culture. CONCLUSION: There is a
      difference among the predominant variants of major house dust mite allergens in
      different geographical regions.

PMID- 18637584
TI  - [Spatial distribution pattern of Oncomelania hupensis population in marshland and
      lake area].
AB  - OBJECTIVE: To explore the spatial pattern of the distribution of Oncomelania
      hupensis population in marshland and lake region. METHODS: Four bottomlands were
      selected randomly for the investigation along the Qiupu River in Guichi District,
      Anhui Province. The quadrats were placed randomly for snail survey, and the mean
      crowding, mean density, aggregation indices (diffusion coefficient (C), morisita
      index (Idelta), index of patchiness (m*/m) ), Taylor's power law and Iwao's m*-m
      regression index were analyzed. RESULTS: For 4 bottomlands in different time, the
      diffusion coefficients, Morisita indices, and m*/m indices were all more than
      one. There was a close linear relationship between the logarithm of the snail
      density and its variance (P < 0.01), and the correlation coefficient was 0.972.
      In Taylor's power law, the lg a was 0.602 and b was 1.427. There was a close
      linear relationship between the mean crowding (m*) and the snail density (m) (P <
      0.01), and the correlation coefficient, alpha and beta was 0.984, 2.367 and 1.617
      respectively. CONCLUSION: The spatial pattern of Oncomelania hupensis population
      shows an aggregation distribution in marshland and lake region, and the basic
      components of snail distribution are in colonies.

PMID- 18637585
TI  - [Malaria situation in Yunnan Province during 2001-2005].
AB  - OBJECTIVE: To analyze the trends of malaria incidence from 2001 to 2005 in Yunnan
      Province. METHOD: Malaria data in 2001-2005 were collected and statistically
      analyzed by using Microsoft excel 2003 and ArcView GIS 3.3 software. RESULTS:
      Among 63,562 malaria cases reported in the 5 years from 129 counties of 16
      prefecture in the province, the average annual malaria incidence was 3.049/10,000
      with an increase of 4.67% than the previous 5 years chi2 = 63.15, P < 0.05).
      There were 2 peaks of malaria incidence: May to August and October to November.
      Five prefectures with the highest malaria incidence were the prefecture bordering
      to the southern nations, and counties ranged first ten places of malaria
      incidence were all at the first line border areas besides Liang-He County which
      is in the second line border area. There were 23 counties with malaria incidence
      higher than 5 per ten thousand, occupying 80. 31% of all cases in the province
      but only 12.74% of the population. 87.30% of the cases and 79.36% of the death
      occurred in those under 45 years-old. Farmers, laborers and students were at the
      high-risk of malaria infection. Moving population accounted for 17.06% of the
      cases and 23.42% of the death in the province. CONCLUSION: Malaria is still an
      important part of public health in Yunnan Province, and people younger than 45
      years-old, farmers, laborers and moving population are at the high risk for
      malaria infection.

PMID- 18637586
TI  - [Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine in the
      treatment of uncomplicated falciparum malaria in Hainan, China].
AB  - OBJECTIVE: To assess the therapeutic efficacy of the combinations
      dihydroartemisinin-piperaquine and artemether-lumefantrine in treating
      uncomplicated falciparum malaria cases in an area with high level resistance of
      Plasmodium falciparum to chloroquine in Hainan Province. METHODS: Patients aged 1
      to 60 with uncomplicated P. falciparum infection and parasite density 1,000 to
      200,000 parasites/microl were enrolled following an informed consent. Eligible
      patients were randomly assigned to 2 groups for receiving either a 3-day course
      of dihydroartemisinin-piperaquine (40/320 mg, DP, group A) or 6-dose course of
      artemether/lumefantrine (20/120 mg tablets, AL, group B) over three days. They
      were followed up with clinical and laboratory examinations until day 28 using
      standard WHO in vivo antimalarial drug test protocol. RESULTS: Altogether 107
      eligible patients were enrolled but 106 completed the study. Adequate clinical
      and parasitological response (ACPR) was observed in 51 (100%) and 55 (100%) cases
      in groups A and B respectively. The mean time of fever clearance and mean time of
      asexual parasite clearance were (20.99 +/- 11.38) h and (36.45 +/- 12.60) h in AL
      and (22.35 +/- 13.26)h and (34.99 +/- 12.28) h in DP, respectively. There was no
      statistical difference on the mean time of fever clearance and asexual parasite
      clearance between AL and DP (P > 0.05). None of the participants showed
      recrudescence and serious adverse effect. CONCLUSION: Both combinations
      artemether-lumefantrine and dihydroartemisinin-piperaquine show a high cure rate
      and proper tolerability among the patients with uncomplicated falciparum malaria
      in Hainan.

PMID- 18637587
TI  - [Diagnosis and treatment of trichinellosis].
AB  - Lack of specific symptoms and signs makes clinical diagnosis of trichinellosis
      difficult. Epidemiological information is important, such as a history of
      ingesting raw or undercooked meat. An outbreak can be traced to a group of people
      dining together. Usual manifestations include abdominal pain or diarrhea with
      general discomfort in the enteric stage, and fever, eyelid or facial edema,
      muscle pain in acute stage. Complications, such as myocarditis, pneumonia,
      encephalitis, may develop in severe cases. Eosinophilia appears between 2 and 5
      weeks after infection. Enzyme-linked immunosorbent assay (ELISA) using the
      excretory-secretory (ES) antigens of the muscle larvae or synthetic tyvelose as
      antigen is sensitive and specific, the serological method ,of choice as a
      screening test. Western blotting is needed to confirm the positive ELISA.
      Definitive diagnosis depends on the finding of larvae in a muscle biopsy
      specimen. Albendazole is the drug of choice for its treatment, 20-30 mg/(kg x d),
      two times daily for 5-7 days. Glucocorticosteroids are given only to severe cases
      and always be used in combination with albendazole, since they could prolong the
      intestinal phase of the infection and increase the muscle larval burdens.

PMID- 18637588
TI  - [Research progress on the action of praziquantel on voltage-gated Ca2+ channel in
      schistosomes].
AB  - Pharmacological actions of praziquantel against schistosome adult worms are
      thought to be directly linked to the disruption of Ca2+ homeostasis. The voltage
      gated Ca2+ channel is an important factor in regulating the intracellular Ca2+
      level. Studies have revealed that Ca2+ channel subunits may be the target for the
      action of praziquantel. This review summarizes the progress on the structure and
      function of the Ca2+ channel of Schistosoma spp and other Platyhelminths as well
      as the role of Ca2+ channel in action of praziquantel.

PMID- 18637589
TI  - [Dendritic cells and Th2 response induced by schistosome infection].
AB  - Dendritic cells act as the major antigen presenting cells in the body and play a
      central role in intriguing the adaptive immune response. Protective immunity
      against schistosome and immuno-pathological response in host caused by eggs are
      both closely associated with Th2 response. Further understanding on immune
      mechanism will contribute to the development of vaccines against schistosome
      infection, as well as the relief of the pathological lesion in schistosomiasis.
      This article discusses the central role of dendritic cells in the mechanism of
      Th2 response induced by schistosome (including eggs).

PMID- 18637590
TI  - [Experimental treatment using combined Fructus psoraleae and dihydroartemisinin
      in mouse cryptosporidiosis].
AB  - A combination of Fructus psoraleae (3.4 g/kg) and dihydroartemisinin (60 mg/(kg x
      d)) was used for 7 d in mice infected with Cryptosporidium parvum infection
      induced by oral administration of dexamethasone. The results indicated that
      number of Cryptosporidium parvum oocysts in feces, proportion of CD4+, CD3+ T
      lymphocytes in blood, serum IFN-gamma, and nitric oxide (NO) content in
      intestinal tissue were all higher than those of infected control group (P <
      0.01). The pathogenic change in intestine of treated mice was lighter than that
      of infected control. It indicates that the combination of Fructus psoraleae and
      dihydroartemisinin is effective to mice cryptosporidiosis probably through
      upregulating serum IFN-gamma, proportion of CD4+ and CD3+ T cells and NO
      concentration in intestine.

PMID- 18637591
TI  - [Sampling survey on schistosomiasis in Jingzhou City in 2006].
AB  - A survey on schistosomiasis conducted in sampled 453 out of 1971 villages in
      Jingzhou City in the year of 2006. Miracidia hatching test demonstrated that the
      prevalence in human population was 3.9% (12,006/310,232), with sporadic cases of
      acute schistosomiasis, and the prevalence in cattle was 10.2% (270/2,651). The
      mean density of living snails was 0.67/0.11 m2 (1,988/1,054,597) with a density
      of infected snails of 0.001 9/0.11 m2 (1,988/713,486). In comparison to those of
      2004, prevalence in humans decreased by 40.0%, prevalence in cattle increased by
      22.3%; the snail-ridden area increased by 4.0%, but the mean density of living
      snails increased by 68.5% and the infected snail density increased by 18.8% with
      a decrease of 36.4% in snail infection rate. Consequently, there is an urgent
      need in controlling schistosome infection in cattle.

PMID- 18637592
TI  - [Minimum dose of Trichinella spiralis muscle larvae to infect mice].
AB  - Seventy male mice (Kunming strain) were randomly divided into 7 groups (10 mice
      per group), each mouse was orally inoculated with 30, 25, 20, 15, 10, 5 or 3
      muscle stage larvae of Trichinella spiralis, respectively. All infected mice were
      sacrificed 6 weeks post-inoculation, number of larvae per gram (LPG) of diaphragm
      were counted by compression method (trichinelloscopy), the carcass was digested
      by artificial digestion method and LPG was counted. The larval detection rate by
      trichinelloscopy and digestion method was 100% (10/10) in all mice infected with
      30, 25, 20, 15 or 10 larvae, but 70% (7/10) and 100% in mice infected with 5
      larvae, respectively. No larva was found by either method in mice infected with 3
      larvae. There is a positive correlation between the larval burden (of diaphragm
      and muscle) and the infecting dose (r = 0.759, P < 0.05; r = 0.638, P < 0.05),
      and the minimum infection dose to a mouse is 5 larvae.

PMID- 18637593
TI  - [Paragonimus skrjabini infection in animal reservoir hosts and questionnairing in
      residents at a village of Hubei Province].
AB  - Freshwater crabs (Sinopotamon denticulatum) were examined for metacercariae. Cats
      and dogs were also examined for Paragonimus infection. Questionnairing was
      carried out on health knowledge and behaviors among local residents in a village
      of Baokang County, Hubei Province. Results showed that the infection rate of
      Paragonimus skrjabini metacercariae in Sinopotamon denticulatum was 20.5%
      (46/214), with 15.6% (20/128) in a mining area and 30.2% (26/86) for the non
      mining area respectively (chi2 = 6.5, P < 0.05). The prevalence in cats and dogs
      was 25.0% (6/24) and 17.6% (6/34) respectively (chi2 = 0.46, P > 0.05).
      Questionnairing showed that dogs and cats were with the habit of foraging and
      defecating at streams and children had the habits of eating raw or under-cooked
      crabs. The natural and ecological environments are in favor of the life cycle of
      P. skrjabini.

PMID- 18637594
TI  - [Investigation on species composition of cockroaches and bacteria-carrying on
      their bodies in five cities of Hainan].
AB  - "ZA-type" cages were used to capture cockroaches in 267 sites of 5 cities in
      Hainan. Species were identified and bacteria were isolated by routine method. 441
      cockroaches were collected and identified as five species belonging to two
      genera, 75.3% being Periplaneta americana. More cockroaches were found in
      sewerage. Bacteria were detected from 82.4% of cockroaches, including Escherichia
      coli, Pseudomonas aeruginosa, Salmonella sp, Staphylococcus aureus, Shigella sp,
      Bacillus proteus and sort of mycetes. Therefore, the dominant species is
      Periplaneta americana in Hainan, and the high bacteria-carrying behavior of
      cockroaches indicates its importance in disease transmission.

PMID- 18637595
TI  - [Investigation on an outbreak of trichinosis and clinical analysis].
AB  - An outbreak of trichinosis occurred in Lhingchi Prefecture of Tibet with 9 cases
      identified among 10 people. They consumed collectively raw or undercooked pork.
      Two cases died because of misdiagnosis and mistreatment. In the 9 cases, 3 had
      eosinophilia, 3 showed positive anti-Trichinella IgG. Trichinella larvae were
      found in gastrocnemius muscle of 3 cases by biopsy including the 2 died
      cases.Seven cases were successfully treated with albendazole.

PMID- 18637596
TI  - Carcinoid disease and anesthesia.

PMID- 18637597
TI  - Total intravenous anesthesia (TIVA) for carcinoid syndrome--a case report.

PMID- 18637598
TI  - The simulation theatre: a means to enhanced learning in the 21st century.
AB  - The increasing role of simulation in medical education has paralleled advancement
      of this technology. Full environment simulation (FES) can be employed to
      effectively replicate rare medical catastrophes with exacting realism. It has
      been suggested that emotion can significantly enhance learning by producing
      memories that are processed and stored via the amygdaloid complex which is
      relatively impervious to extinction and thus forgetting. Theoretically the
      addition of emotional content to simulated crises during FES can be used to
      affect such changes in the participants and thus facilitate learning. We discuss
      the theoretic benefit and the use of FES with emotional enhancement as it relates
      to improved memory and learning.

PMID- 18637599
TI  - Anesthetic care of the patient for robotic surgery.

PMID- 18637600
TI  - Assessment of perioperative transfusion therapy and complications in sickle cell
      disease patients undergoing surgery.
AB  - BACKGROUND: Perioperative blood transfusion is usually given to sickle cell
      disease patients to reduce or prevent perioperative morbidity. Assessment of such
      a practice was the subject of our study. METHODS: A retrospective one year survey
      of sickle cell disease patients undergoing surgery at Salmaniya Medical Complex,
      Bahrain was conducted. The medical records were reviewed to characterize the
      surgical procedure, transfusion management and perioperative complications.
      RESULTS: 85 sickle cell disease patients who underwent surgery were studied.
      Preoperatively, 21.2% had exchange transfusion (ETX), 24.7% had simple
      transfusions (STX) and 54.1% had no transfusion (NTX). 14.1% of all patients had
      postoperative complications, and 50% of those, had complications from the
      laparoscopic cholecystectomy group. The incidence of sickle cell crisis
      postoperatively was 22.2% in ETX group, 9.5% in STX group and 4.34% in the NTX
      group. The incidence of acute chest syndrome postoperatively was found to be
      5.55% in the ETX group, 4.76% in the STX group and 4.34% in the NTX group. No
      intraoperative complications were recorded in all groups. All patients who had
      postoperative complications had a preoperative HBSS > 40%. CONCLUSION: Exchange
      transfusion does not prevent perioperative complications of sickle cell disease
      patients. HBSS > 40% carries a higher risk of postoperative complications.

PMID- 18637601
TI  - Methemoglobin levels during epidural anesthesia for renal transplantation-
      comparison of prilocaine with bupivacaine.
AB  - BACKGROUND AND OBJECTIVE: One goal of anesthesia for renal transplantation is to
      avoid an excess load to be imposed on the newly functioning kidney, by using
      appropriate agents and dosages in the perioperative management. The purpose of
      this study was to investigate the effect of prilocaine on serum methemoglobin
      levels when used as the local anesthetic in epidural anesthesia for renal
      transplantation, and to compare its effects with that of bupivacaine, which is
      the standard local anesthetic used. METHODS: 26 adult renal recipients were
      randomized into 2 equal groups according to the local anesthetic used for
      epidural anesthesia during the operation. Patients in group P (n = 13) were given
      prilocaine and those in group B (control, n = 13) received bupivacaine. The
      methemoglobin measurement intervals were at: baseline before administration of
      local anesthetic, and then at 2 hours, 5 hours, and 12 hours of local anesthetic
      administration. RESULTS: Methemoglobin levels in the prilocaine group were above
      the normal range in all measurements other than baseline. In the bupivacaine
      group, methemoglobin levels increased only at 5 hours of local anesthetic
      administration. However, methemoglobin concentrations and hemoglobin levels were
      comparable between the two groups at all time intervals, and none of the patients
      demonstrated clinical symptoms. CONCLUSION: The use of prilocaine in epidural
      anesthesia for renal transplantation surgery resulted in an increase in
      methemoglobin levels, which did not cause any clinical symptoms and was similar
      to those of bupivacaine at all time measurements.

PMID- 18637602
TI  - Analgesic requirements for patients undergoing lower extremity orthopedic surgery
      -the effect of combined spinal and epidural magnesium.
AB  - BACKGROUND: Polypharmacological approach is the most common practice to treat
      perioperative pain, as no single agent has yet been identified to specifically
      inhibit nociception without associated side effects. Opioids such as Fentanyl is
      commonly added to local anesthetics to produce spinal and epidural anesthesia.
      However, significant adverse effects, such as pruritus, respiratory depression,
      hemodynamic instability and occasionally severe nausea and vomiting, may limit
      their use. Our present study was designed to assess the effectiveness of using
      combined intrathecal and epidural magnesium (Mg) in reducing intra-and
      postoperative analgesic requirements and improving the quality of analgesia.
      METHOD: Eighty patients ASA I, II, III who scheduled for lower extremity
      orthopedic surgery were included in the study. Patients were randomly allocated
      to one of two groups, 40 patients each. The Control Group: patients received
      intrathecal 10 mg of Bupivacaine 0.5% (2 ml), plus 25 microg of Fentanyl (0.5
      ml), plus 0.9% NaCl solution (1 ml) and an epidural infusion of 0.9% NaCl at a
      rate of 5 ml/hr. The Magnesium Group: patients received intrathecal 10 mg of
      Bupivacaine 0.5% (2 ml), plus 25 microg of Fentanyl (0.5 ml), plus 50 mg of 5% Mg
      (1 ml) and an epidural infusion of 2% Mg at a rate of 100 mg/hr (5 ml/hr).
      RESULTS: Intrathecal Mg prolonged fentanyl analgesia as indicated by increased
      duration of anesthesia in the Mg group, and thus improving the quality of spinal
      anesthesia. The effectiveness of the postoperative analgesia was confirmed by
      markedly lower perioperative analgesic requirements (38.3 % less than the Control
      group), the patient's low VAS score, the longer time for the patients first
      requirements of post-operative analgesia in the Mg group. CONCLUSION: For lower
      extremity orthopedic procedure, supplementation of spinal anesthesia with
      combined intrathecally injected and epidurally infused Mg, considerably reduced
      the perioperative analgesic requirements without any side effects.

PMID- 18637603
TI  - The feasibility of spinal anesthesia with sedation for laparoscopic general
      abdominal procedures in moderate risk patients.
AB  - BACKGROUND: One of the major advantages of laparoscopic surgery is minimizing
      postoperative morbidity. The previous limitations to the use of spinal anesthesia
      in laparoscopic surgery were the limited work space, high failure rate, more
      intra-operative morbidity and significant arterial blood gas alterations.
      However, the addition of a small-dose Ketamine infusion to propofol might provide
      a suitable sedative combination to be used with high spinal anesthesia, producing
      titerable sedation, increased hemodynamic stability, and minimal respiratory
      depression. PATIENTS AND METHODS: At KFSH & RC Hospital, after Ethical Committee
      approval and informed written consent, 18 ASA III patients scheduled for various
      laparoscopic abdominal procedures were enrolled. Exclusion criteria consisted of
      ejection fraction below 45% and or peak expiratory flow rate and forced vital
      capacity of less than 65% of predicted values. Following oral premedication with
      midazolam 7.5-10 mg 30 min preoperatively, spinal anesthesia was conducted by
      bupivicaine 0.75% 3-3.5 ml at L3-4, in the lateral position to reach a sensory
      level at T4. Sedation was started by intravenous injection of 0.4 mg/kg propofol
      and 0.1 mg/kg ketamine prior to spinal anesthesia. This was followed by infusion
      of 1.0-1.5 mg/kg/h and 0.3-1.0 mg/kg/h. of the same drugs respectively. The
      sedation requirements were adjusted to keep the patient sleepy with conservation
      of airway reflexes at level 3 on a 5 point sedation score. Heart rate,
      respiratory rate and SpO2 were monitored, together with direct arterial blood
      pressure monitoring and arterial blood gas analysis through arterial cannulation.
      Postoperative first time call for analgesia, total morphine consumption during
      the first hour and incidence of complications were recorded. Twenty Four hours
      later, surgeons' and patients' satisfaction were obtained and recorded. RESULTS:
      Heart rate and mean arterial blood pressure were significantly decreased after
      spinal anesthesia and intra-peritoneal insufflations of CO2, with significant
      increase in arterial carbon dioxide tension accompanied by increase in the
      respiratory rate. The increase in respiratory rate led to gradual decrease of CO2
      level down to near the pre-operative PaCO2 values. However, there was
      insignificant decrease in oxygen saturation throughout the intra-operative time.
      Postoperatively there were excellent surgeon and patient's satisfaction. Only one
      patient regained sensation before completion of surgery and sedation was deepened
      to level 5 sedation score. The mean surgical time was 98.5 +/- 21.4 min while the
      mean anesthesia time was 117.7 +/- 20.1 min. First mean time call for analgesia
      was 50 +/- 8 min. 7/18 patients required single dose of morphine of 4 mg during
      the 1st hour postoperatively. CONCLUSIONS: The addition of a sedative combination
      of ketamine and propofol to spinal anesthesia was found to be safe and efficient
      from both the anesthetic and surgical point of view, especially for sick patients
      with intermediate clinical predictors.

PMID- 18637604
TI  - Effects of butorphanol and fentanyl on cerebral pressures and cardiovascular
      hemodynamics during tunneling phase for ventriculoperitoneal shunt insertion.
AB  - PURPOSE: Subcutaneous tunneling for ventriculoperitoneal shunt insertion is the
      most painful step of this surgery. It is associated with intense hemodynamic
      response, may influence the intracranial pressure, and thus may worsen the
      existing intracranial pathology. The purpose of this report is to evaluate the
      commonly used opioid fentanyl, along with butorphanol, an agonist-antagonist
      compound. METHODS: Twenty adult patients undergoing ventriculoperitoneal shunt
      surgery were induced with fentanyl 2-mcg.kg(-1) and thiopentone 4-5 mg.kg(-1).
      Intubation followed the administration of rocuronium 1 mg.kg(-1). All patients
      were put on mechanical ventilation to maintain end-tidal carbon dioxide levels of
      32 +/- 2 mmHg. Anesthesia was maintained with isoflurane in N2O and O2 (MAC 1.0
      +/- 0.2). Routine monitoring, arterial blood pressure and intracranial pressures
      were measured. Three minutes prior to the tunneling phase, patients received
      either fentanyl 1 mcg.kg(-1) or butorphanol 1 mg in a randomized manner.
      Thereafter hemodynamic and intracranial pressure changes were noted during
      tunneling and each minute in the post-tunneling period for 5 minutes. The
      duration of the tunneling phase was also noted. Data were presented as number
      (proportion) or mean +/- SD/median (range) as appropriate. Statistical analysis
      was done using Wilkoxon ranksum test and the repeated measures of ANOVA. The
      value of p < 0.05 was considered significant. RESULTS: A significant rise in the
      intracranial pressure and cerebral perfusion pressure along with the hemodynamic
      parameters was noted during the tunneling phase in both groups. The changes were
      of longer clinical duration in the butorphanol group. CONCLUSION: Butorphanol
      must be used with caution in neurosurgical patients. The ventricular end of the
      shunt catheter should preferably be put before the tunneling phase to avoid rise
      in intracranial pressure.

PMID- 18637605
TI  - Comparison of percutaneous dilatational tracheostomy with surgical tracheostomy.
AB  - RATIONALE: Tracheostomy is done mostly in critically ill patients, many of whom
      may not survive. We still do not know the long term complications of tracheostomy
      itself; tracheal and subglottic stenosis, and tracheomalacia. OBJECTIVES: To
      compare the complications of surgical tracheostomy (ST) versus percutaneous
      dilatational tracheostomy (PDT) by means of MRI control up to 1 month after
      closed tracheostomy. RESULTS: There was no death related to tracheostomy. In both
      groups there were two preoperative complications: one minor hemorrhage and one
      subcutaneous empysema in the ST group, and one minor bleeding and one puncture
      ofendotracheal tube cuff in the PDT group. When the early and the late
      postoperative complications of the two groups were compared, it was observed that
      in the ST group, five early (one minor bleeding, three stomal infections and one
      accidental decannulation), and two late (one peristomal granuloma and one
      persistent stoma) postoperative complications had occurred. In the PDT group,
      four early (minor bleeding) and two late postoperative complications (two minor
      bleeding) were observed. MRI of two patients in the PDT group demonstrated
      tracheal stenosis. CONCLUSIONS: PDT is as safe and as effective as ST. Although
      the early and late postoperative complication rates were not significant in the
      PDT group, we believe that further investigations with larger groups are
      necessary to find long-term outcome following PDT. MRI scanning provides an
      excellent non-invasive method of assessing the tracheal lumen.

PMID- 18637606
TI  - Bilateral tension pneumothorax and pneumoperitonium during laser pediatric
      bronchoscopy--case report and literature review.
AB  - We describe a case of a fifteen month old girl with a previous history of
      partially repaired congenital heart disease, presented for diagnostic
      bronchscopic evaluation of mid-tracheal narrowing. Intraoperatively, the surgical
      team decided to perform a transbronchoscopic laser resection of a granulation
      tissue over the previously placed airway stent. After repeated airway
      manipulations, the patient developed intraoperative bilateral tension
      pneumothoracis as well as tension pneumoperitonium. These complications were
      recognized, diagnosed and promptly treated and patient made full recovery. This
      paper presents a case details, reviews the literature about these life
      threatening complications and suggests ways to prevent poor outcomes.

PMID- 18637607
TI  - Tachyphylaxis to cisatracurium--case reports and literature review.
AB  - Nondepolarizing neuromuscular blocking agents (NNMBAs) are commonly used in the
      intensive care unit (ICU), mainly to facilitate mechanical ventilation in
      critically ill patients who are not responding to sedatives and analgesics alone.
      Tachyphylaxis, also referred to as resistance, may develop during long-term
      infusion of NNMBAs. Several case reports of tachyphylaxis to NNMBAs have been
      reported. Although the definite mechanisms of tachyphylaxis to NNMBAs are not
      clear, several pharmacodynamic and pharmacokinetic changes have been described
      with the development of resistance. Tachyphylaxis to NNMBAs is associated with
      adverse outcomes including inadequate ventilation, increased risk of dose
      dependent side effects, and increased drug costs. Patients who develop
      tachyphylaxis to one NNMBA should be treated with another NNMBA if neuromuscular
      blockade (NMB) is still indicated. We report three cases of tachyphylaxis to
      cisatracurium in a surgical intensive care unit (SICU): one in patient with acute
      respiratory distress syndrome (ARDS) and the other two with traumatic brain
      injury (TBI).

PMID- 18637608
TI  - Cervical stabilization with halo fixation: anesthetic implications--case reports.
AB  - Halo fixation is often used to provide stability in patients with unstable
      cervical spine. These fixation devices pose unique challenges to the
      anesthesiologists encountered while securing an airway. Management of airway in
      patients with halo fixation is complicated by the fixed position, limited access
      to the face, and immobilization of neck. We managed two different patients, one
      in which halo fixation was done for atlanto-axial dislocation (AAD); and the
      other, who came with halo fixation and underwent wound debridement under general
      anesthesia. In the former case, procedure was carried out with laryngeal mask
      anesthesia and patient breathing spontaneously whereas, in the later case,
      procedure was performed after securing the airway using awake fiberoptic
      intubation technique.

PMID- 18637609
TI  - Anesthesia management of a Jehovah's Witness patient with pheochromocytoma
      undergoing off pump coronary artery bypass graft surgery--acase report.
AB  - Concomitant coronary artery disease (CAD) and pheochromocytoma are rare. Patients
      with advanced CAD requiring coronary artery bypass graft (CABG) surgery and
      clinically active pheochromocytoma present a challenge to anesthesiologists. The
      risk is much higher if the patient is an anemic Jehovah's Witness because these
      patients refuse to receive blood or blood products, even when faced with a life
      threatening hemorrhage. To our knowledge, this is the first case to describe the
      anesthetic management of an anemic Jehovah's Witness patient with
      pheochromocytoma presenting for off-pump CABG surgery.

PMID- 18637610
TI  - Cesarean hysterectomy for placenta percreta invading the anterior abdominal wall:
      anesthetic considerations--a case report.
AB  - Placenta accreta is defined as an abnormal adherence of the placenta to the
      uterine wall owing to a faulty or an absent decidua basalis. Placenta accreta is
      further subdivided into placenta accreta vera, increta and percreta, depending on
      the level of invasion of the uterine wall and surrounding structures. Placenta
      percreta represents invasion to the serosa and/or other pelvic structures. We
      herein present the case of a pregnant patient with placenta percreta invading
      anterior abdominal wall and review the perioperative (Cesarean hysterectomy)
      anesthetic management of this complication.

PMID- 18637612
TI  - Platelet transfusion in a patient with thrombotic thrombocytopenic purpura
      presenting for splenectomy--a case report.

PMID- 18637611
TI  - Hemodynamic effects of anesthetic induction in patients treated with beta and
      calcium channel blockers.
AB  - BACKGROUND: The response to anesthetic induction and airway manipulation in the
      presence of cardiovascular disease and antihypertensive therapy has not been
      adequately investigated. METHODS: The blood pressure, pulse pressure and heart
      rate changes at induction and following tracheal intubation were compared in
      patients who were on either preoperative beta-adrenergic blocker therapy (BB
      group, n = 20) or a combination of beta-adrenergic blocker and calcium channel
      blocker therapy (BB + CCB group, n = 20). A standardized anesthesia induction
      protocol was followed, in the two gourps. RESULTS: No statistical difference was
      observed in the hemodynamic parameters between the two groups. The total number
      of hypotensive patients (SAP 90 <mmHg) and bradycardic episodes following
      induction of anesthesia were one in the BB group and eighteen in BB + CCB group
      and were treated with ephedrine (p = 0.000002). Two episodes of hypotension
      without bradycardia occurred in BB group and six in BB + CCB group and were
      treated with phenylephrine (p = 0.25). CONCLUSION: Hypotension requiring
      treatment in patients receiving a combination of BB + CCB is more frequent after
      induction of anesthesia.

PMID- 18637613
TI  - Anesthetic management of a patient with myotonic dystrophy for laparoscopic
      cholecystectomy--a case report.
AB  - Myotonic dystrophy (MD) is rare disease that offers challenges to
      anesthesiologists. We report a case of adult patient with myotonic dystrophy who
      underwent laparoscopic cholecystectomy. A 48-year-old male patient, known case of
      MD, was presented for laparoscopic cholecystectomy. Physical examination
      revealed, young man, calm, quite, cooperative, not in pain or distress with
      frontal baldness, temporal bone recession, elongated face, mild degree of ptosis
      and swan neck. Under complete aseptic conditions, thoracic epidural T6-7 with
      catheter insertion was performed while the patient was placed on left lateral
      side. Plain bupivacaine 0.5% 7cc was injected through the catheter. Level of
      analgesia tested with ice reached up to T4. Intravenous sedation was achieved
      with midazolam 2 mg and ketamine 50 mg. The patient was comfortably lying supine
      on warm heated mattress, except of bilateral shoulder pains which was relieved
      with midazolam and ketamine. In conclusion, regional anesthesia, spinal or
      epidural, is preferable in MD patients. Shoulder pains is the main intraoperative
      problem encountered in our patient. Therefore, studies are needed for treating
      shoulder pain. To the best of our knowledge, this is the first case report in a
      patient with MD who underwent laparoscopic cholecystectomy under thoracic
      epidural analgesia. Myotonic dystrophy (M) is rare disease and represents
      challenges to anesthesiologists. We report a case of adult patient with myotonic
      dystrophy who underwent laparoscopic cholecystectomy.

PMID- 18637614
TI  - Anesthesia with etomidate and remifentanil for cesarean section in a patient with
      severe peripartum cardiomyopathy--a case report.
AB  - Patients with peripartum cardiomyopathy may require analgesia/anesthesia for
      delivery or cesarean section. Many different methods of anesthesia has been used
      for this purpose. Remifentanil was used safely in peripartum cardiomyopathic
      patients, but there is not any report about etomidate usage in such patients. We
      report on a 19 years old patient, at 32 weeks of gestation, with severe
      peripartum cardiomyopathy, in uncompensated heart failure and pulmonary edema.
      She was scheduled for emergency cesarean section becaue of threatening mother's
      life and fetal distress. General anesthesia was induced with etomidate and
      maintained with remifentanil infusion safely, without any adverse outcome on
      mother or newborn.

PMID- 18637615
TI  - The combined effect of ketamine and remifentanil infusions as total intravenous
      anesthesia for scoliosis surgery in children.
AB  - BACKGROUND: This study was designed to assess the effect of combination of
      ketamine and remifentanil infusions as total intravenous anesthesia (TIVA) during
      scoliosis surgery in children. METHODS: Thirty two children, 8-14 yr of age,
      scheduled for posterior spinal fusion, were randomly allocated into two equal
      groups to receive either remifentanil infusion in a dose of 0.2 microg/kg/minutes
      or same dose of remifentanil infusion combined with ketamine infusion in a dose
      of 1 microg/kg/minutes after induction of general anesthesia. During surgery,
      hemodynamics, surgical bleeding, and electrophysiology monitors were recorded.
      After completion of surgery, recovery score, recovery time and rescue analgesia
      were assessed in post-anesthesia care unit (PACU) for 24 hours. RESULTS: The two
      groups were similar for age, weight, duration of surgery, and time to extubation.
      Intraoperative heart rate and arterial blood pressure were significantly
      decreased in remifentanil group when compated to remifentanil-ketamine group. The
      surgical bleeding and electrophysiological monitoring were not significantly
      affected by remifentanil-ketamine combination in second group. Recovery score and
      recovery time were not significantly increased in remifentanil-ketamine group.
      First pain scores recordings in arrival to (PACU) were significantly less in
      remifentanil-ketamine group than remifentanil group and the time passed to first
      patient controlled analgesia (PCA) demand dose was increased in remifentanil
      ketamine group. The first 24 h morphine consumption was 38 +/- 17 and 28 +/- 10
      mg (mean +/- SD) in remifentanil and remifentanil-ketamine groups, respectively.
      CONCLUSIONS: These data demonstrate that during posterior spinal fusion surgery
      in children, the combination of ketamine and remifentanil infusions as TIVA may
      provide hemodynamic stability, satisfactory surgical requirements with reliable
      electrophysiological monitoring and adequate post operative pain relief
      supplemented by PCA morphine.

PMID- 18637616
TI  - Herbal intake: undiagnosed hypothyroidism leading to postoperative refractory
      circulatory collapse--a case report.
AB  - There is a high probability of missing out on the preoperative diagnosis of
      hypothyroidism in elderly females, as most of the symptoms are attributed to old
      age. We report a patient with undiagnosed hypothyroidism, operated for excisional
      biopsy of carcinoma of tongue, who postoperatively developed septicemia
      refractory to maximum ionotropic support and antibiotic coverage and succumbed
      within 40 hours. Her symptoms of constipation, sedentary life style, and joint
      pains were attributed to old age by the family and thus were not communicated to
      us in the preoperative assessment. Her long-standing hypothyroidism probably was
      associated with adrenocortical suppression exaggerated with intermittent and
      chronic ingestion of herbal powder, which generally contains steroids. We
      recommend that a more careful preoperative evaluation and history pertaining to
      hypothyroidism in obese female patients more than 45 years with joint pains
      should be sought for. Ingestion of herbal powders should alert us as these
      contain steroids If there is a suspicion of hypothyroidism, then elective surgery
      should be deferred to rule out the same due to possibility of progression to
      myxedema coma under stress of anesthesia and surgery. We also recommend that in
      these cases preoperative blood cortisol level should be evaluated to rule out
      adrenocortical suppression and direct its management, if present.

PMID- 18637617
TI  - Recurrent postoperative aspiration following jugular foramen tumor resection.
AB  - We report a 38 year old male patient who underwent a craniotomy for jugular
      foramen tumor resection. In the postoperative care unit, the patient developed
      aspiration accompanied with oxyhemoglobin desaturation. Subsequently, he had
      several episodes of recurrent aspiration which were attributed to cranial nerves
      (IX, X) palsy as a complication of the surgery at the jugular foramen. It is
      suggested that aspiration prophylactic measures should be taken and early
      assessment of lower cranial nerves function should be done prior to tracheal
      extubation to decrease post-operative aspiration in patients undergoing base of
      skull surgery.

PMID- 18637618
TI  - Rupture of intracranial aneurysm after partial clipping due to aspiration
      drainage system--a case report.
AB  - In neurosurgical practice, extradural or subgaleal drains are commonly placed and
      connected to a vacuum system. Several reports have described severe bradycardia
      or arterial hypotension, or both, after connection of negative suction pressure
      to the extradural or epicranial drains following craniotomy. We encountered an
      unusual complication with the use of the vacuum drain after an elective
      aneurysmal clipping surgery. Our case is an iatrogenic intracranial hypotension
      leading to a clinically significant and potentially fatal complication.

PMID- 18637619
TI  - National health insurance on the horizon for South Africa.

PMID- 18637620
TI  - Inconsiderate CPD decision.

PMID- 18637621
TI  - Pagophagia when ice is not available--drink cold water.

PMID- 18637622
TI  - Am I just an old-fashioned GP?

PMID- 18637623
TI  - Electronic data interface in general practice improves debtor days.

PMID- 18637624
TI  - Public sector ARV sites finding 'disturbing'.

PMID- 18637625
TI  - Australian surgeon's tenacity more than skin deep.

PMID- 18637626
TI  - More than a pinch less salt needed.

PMID- 18637627
TI  - Child mortality committee launch--a chance missed.

PMID- 18637628
TI  - Co-trimoxazole prophylaxis in HIV: the evidence.

PMID- 18637629
TI  - HPV vaccines: bring me your daughters!

PMID- 18637630
TI  - Auto-amputation of a breast due to ductal carcinoma.

PMID- 18637631
TI  - Progressive multifocal leucoencephalopathy--a case report.

PMID- 18637632
TI  - Paediatric surgery: birth of a new specialty or a coming of age?

PMID- 18637633
TI  - A centile chart for fetal weight for gestational ages 24-27 weeks.

PMID- 18637634
TI  - Eating disorders in South Africa: an inter-ethnic comparison of admission data.

PMID- 18637635
TI  - Coping strategies and social support after receiving HIV-positive results at a
      South African district hospital.

PMID- 18637636
TI  - Medical management of opioid dependence in South Africa.
AB  - Medical practitioners in South Africa are increasingly confronted with requests
      to treat patients with opioid use disorders. Many do not possess the required
      knowledge and skills to deal with these patients effectively. This overview of
      the medical treatment of opioid dependence was compiled by an elected working
      group of doctors working in the field of substance dependence. Recommendations
      are based on current best practice derived from scientific evidence and consensus
      of the working group, but should never replace individual clinical judgement.

PMID- 18637637
TI  - Medical futility and end-of-life care.
AB  - Acceptance of the concept of medical futility facilitates a paradigm shift from
      curative to palliative medicine, accommodating a more humane approach and
      avoiding unnecessary suffering in the course of the dying process. This should
      not be looked upon as abandoning the patient but rather as providing the patient
      and family with an opportunity to come to terms with the dying process. It also
      does not entail withdrawal or passivity on the part of the health care
      professional. In addition to medical skills, the treating physician is
      responsible for guiding this process by demonstrating sensitivity and compassion,
      respecting the values of patients, their families and the medical staff. The need
      for training to equip medical staff to take responsibility as empathetic
      participants in end-of-life decision-making is underscored.

PMID- 18637638
TI  - Adjunctive corticosteroid treatment of clinical Pneumocystis jiroveci pneumonia
      in infants less than 18 months of age--a randomised controlled trial.
AB  - OBJECTIVES: To determine the efficacy and safety of adjunctive corticosteroid
      therapy in clinical Pneumocystis jiroveci pneumonia (PCP) in infants exposed to
      HIV infection. DESIGN: Double-blind randomised placebo-controlled trial. METHODS:
      Infants with a clinical diagnosis of PCP, based on an 'atypical' pneumonia with:
      (i) hypoxia out of proportion to the clinical findings on auscultation; (ii) C
      reactive protein count less than 10 mg/1; (iii) lactate dehydrogenase level above
      500 IU/1; (iv) compatible chest radiograph findings; and (v) positive HIV enzyme
      linked immunosorbert assay (ELISA) were included in the study. Patients were
      randomised to receive either prednisone or placebo. The protocol provided for the
      addition of prednisone to the treatment at 48 hours if there was clinical
      deterioration or an independent indication for steroid therapy. Other treatment
      was carried out in accordance with established guidelines. The primary study
      endpoint was in-hospital survival. Secondary outcome was time from admission to
      the first day of mean oxygen saturation above 90% in room air. RESULTS: One
      hundred patients were included, 47 in the prednisone and 53 in the placebo group.
      Patients in the prednisone group had a 43% better chance of survival than the
      placebo group (hazard ratio (HR) 0.57, 95% confidence interval (CI) 0.30 - 1.07,
      p=0.08). No significant differences could be demonstrated between groups with
      regard to other parameters of recovery. CONCLUSIONS: In HIV-exposed infants with
      clinical PCP, adjunctive corticosteroid treatment does not appear to add benefit
      regarding time to recovery or oxygen independency, but early administration may
      improve survival. A large multicentred trial is needed to confirm these findings.

PMID- 18637639
TI  - A review of internal medicine re-admissions in a peri-urban South African
      hospital.
AB  - OBJECTIVE: To measure the re-admission rate and the number of preventable re
      admissions in a secondary-level South African hospital, and to identify factors
      predictive of re-admission. METHOD: The admission register for the medical wards
      at Cecilia Makiwane Hospital (CMH) was used to identify re-admitted patients,
      whose folders were then reviewed. A comparison group of patients who were not re
      admitted was randomly generated from the same register. RESULTS: The re-admission
      rate for the 7 months ending October 2006 was 8.5% (262/3 083). Patients who were
      more likely to be re-admitted had chronic respiratory disease (odds ratio (OR)
      4.2, 95% confidence interval (CI) 1.2 - 14.6), HIV infection (OR 5.0, CI 2.1 -
      12.0), were older than 50 years (OR 5.2, CI 2.5 - 10.9), had a first admission of
      more than 8 days (OR 3.2, CI 1.5 - 6.6) or a booked medical outpatients followup
      (OR 5.1, CI 2.6 - 10.3). Age distribution of re-admissions was bimodal, with HIV
      positive individuals (27.4% overall) accounting for 50% of all admissions younger
      than 50 years, but only 9.1% of those 50 years or older. In individuals older
      than 50 years, 42.1% of admissions were due to chronic cardiorespiratory
      illnesses. Half of re-admissions were judged to be potentially preventable,
      mainly through improved patient education. CONCLUSION: One in 12 general medical
      patients was readmitted. Chronic diseases and inadequate patient education and
      discharge planning accounted for the largest group of re-admissions in older
      patients. Re-admission of HIV/AIDS patients has generated a second peak in
      younger individuals, and the impact of the antiretroviral roll-out on admission
      rates warrants further scrutiny.

PMID- 18637640
TI  - Nuchal translucency as a method of first-trimester screening for aneuploidy.
AB  - OBJECTIVE: To determine the effectiveness of nuchal translucency (NT) screening
      in predicting aneuploidy and structural abnormalities in a South African
      population. STUDY DESIGN: Descriptive study. Setting. Chris Hani Baragwanath
      Hospital fetal medicine unit. OUTCOME MEASURES: An adjusted risk was derived from
      the combination of maternal age-related risk and the risk derived from NT
      screening. A positive screen was denoted by an adjusted risk of more than 1/300
      and a negative screen by an adjusted risk of less than 1/300. In order to
      determine the number of undiagnosed abnormalities in the group, all babies were
      examined by a paediatrician at birth to detect and describe dysmorphic features.
      RESULTS: A total of 428 patients underwent first-trimester screening between July
      2003 and July 2005. Three per cent were lost to follow-up. Of the 415 patients
      analysed, 59 screened positive and 356 screened negative. The mean age for both
      groups of patients was 30.1 years. Of the 57 patients who screened positive, 24
      elected to have chorionic villus sampling (CVS). This resulted in the detection
      of 6 chromosomal abnormalities and 2 structural abnormalities. Among the
      remaining 356 patients, who had screened negative, 2 had an increase in the
      adjusted risk when the risk was compared with the background risk, and 1
      chromosomal abnormality was detected in this group; 8 elected to have CVS because
      of a previous history of a chromosomal abnormality, and there were no
      abnormalities among them. CONCLUSIONS: The use of these screening methods has
      enabled prenatal karyotyping to become cost effective, and allows concentration
      on pregnancies at highest risk for chromosomal abnormalities, regardless of age.

PMID- 18637642
TI  - Evaluation of a sequential global test of improved recovery following stroke as
      applied to the ICTUS trial of citicoline.
AB  - The International Citicoline Trial in acUte Stroke is a sequential phase III
      study of the use of the drug citicoline in the treatment of acute ischaemic
      stroke, which was initiated in 2006 in 56 treatment centres. The primary
      objective of the trial is to demonstrate improved recovery of patients randomized
      to citicoline relative to those randomized to placebo after 12 weeks of follow
      up. The primary analysis will take the form of a global test combining the
      dichotomized results of assessments on three well-established scales: the Barthel
      Index, the modified Rankin scale and the National Institutes of Health Stroke
      Scale. This approach was previously used in the analysis of the influential
      National Institute of Neurological Disorders and Stroke trial of recombinant
      tissue plasminogen activator in stroke.The purpose of this paper is to describe
      how this trial was designed, and in particular how the simultaneous objectives of
      taking into account three assessment scales, performing a series of interim
      analyses and conducting treatment allocation and adjusting the analyses to
      account for prognostic factors, including more than 50 treatment centres, were
      addressed.

PMID- 18637641
TI  - Aging of cerebral white matter: a review of MRI findings.
AB  - BACKGROUND: Cerebral aging is a complex and heterogeneous process that is
      associated with a high degree of inter-individual variability. Structural
      magnetic resonance imaging (MRI) can be used to identify and quantify non-disease
      related aging of the cerebral white matter. METHODS: The present article reviews
      the findings from several MRI techniques, including morphometric approaches,
      study of white matter hyperintensities, diffusion tensor imaging, and
      magnetization transfer imaging, that have been used to examine aging of the
      cerebral white matter. Furthermore, the relationship of MRI indices of white
      matter integrity to age-related cognitive declines is reported. RESULTS: A
      general pattern of age-related preservation and decline emerges indicating that
      the prefrontal white matter is most susceptible to the influence of age. Studies
      that combine MRI with cognitive measures suggest that such age-related reductions
      in white matter integrity may produce a disconnection state that underlies some
      of the age-related performance declines in age-sensitive cognitive domains.
      CONCLUSIONS: White matter aging may contribute to a disconnection state that is
      associated with declines in episodic memory, executive functions, and information
      processing speed.

PMID- 18637644
TI  - Syntheses, structures, and reactivities of borylcopper and -zinc compounds: 1,4
      silaboration of an alpha,beta-unsaturated ketone to form a gamma
      siloxyallylborane.

PMID- 18637643
TI  - Parallel synthesis and screening of polymer-supported phosphorus-stereogenic
      aminophosphane-phosphite and -phosphinite ligands.

PMID- 18637645
TI  - Calcium d States: chemical bonding of CaC6.

PMID- 18637646
TI  - Rapid construction of the cortistatin pentacyclic core.

PMID- 18637647
TI  - Solvent-ligated copper(II) complexes for the homopolymerization of 2
      methylpropene.
AB  - Copper(II) complexes with weakly coordinating counter anions can be utilized as
      highly efficient catalysts for the synthesis of poly(2-methylpropene)
      ("polyisobutene") with a high content of terminal double bonds. These copper(II)
      compounds are significantly more active than the manganese(II) complexes
      described previously, can be applied in chlorine-free solvents such as toluene,
      are easily accessible, and can be handled at room temperature and in laboratory
      atmospheres for brief periods, but they are sensitive to excess water, thereby
      losing their catalytic activity. Replacing the acetonitrile ligands by
      benzonitrile ligands improves the solubility and catalytic activity in nonpolar
      and nonchlorinated solvents. However, the benzonitrile copper(II) compounds have
      lower thermal stability than their acetonitrile congeners.

PMID- 18637648
TI  - Mono- and diprotonation of the superbasic bisguanidine 1,2-Bis(N,N,N',N'
      tetramethylguanidino)benzene (btmgb) and Pt II and Pt IV complexes of chelating
      bisguanidines and guanidinates.
AB  - New Pt complexes of chelating bisguanidines and guanidinate ligands were
      synthesized and characterized. 1,2-Bis(N,N,N',N'-tetramethylguanidino)benzene
      (btmgb) was used as a neutral chelating bisguanidine ligand, and 1,3,4,6,7,8
      hexahydro-2H-pyrimido[1,2-a]pyrimidinate (hpp(-)) as a guanidinate ligand. The
      salts [btmgbH]+[HOB(C6F5)3](-) and [btmgbH2]Cl2 and the complexes [(btmgb)PtCl2],
      [(btmgb)PtCl(dmso)]+[PtCl3(dmso)](-), and [(btmgb)PtCl(dmso)]+[Cl(-)] were
      synthesized and characterized. In the [btmgbH]+ cation the proton is bound to
      only one N atom. In the other complexes, both imine N atoms are coordinated to
      the Pt II, thus adopting a eta2-coordinational mode. The hpp(-) anion, which
      usually prefers a bridging binding mode in dinuclear complexes, is eta2
      coordinated in the Pt IV complex [(eta2-hpp)(hppH)PtCl2(N(H)C(O)CH3)], which is
      formed (in low yield) by reaction between cis-[(hppH)2PtCl2] and H2O2 in CH3CN.

PMID- 18637649
TI  - Experimental measurement of carbohydrate-aromatic stacking in water by using a
      dangling-ended DNA model system.
AB  - Protein-carbohydrate recognition is of fundamental importance for a large number
      of biological processes; carbohydrate-aromatic stacking is a widespread, but
      poorly understood, structural motif in this recognition. We describe, for the
      first time, the measurement of carbohydrate-aromatic interactions from their
      contribution to the stability of a dangling-ended DNA model system. We observe
      clear differences in the energetics of the interactions of several
      monosaccharides with a benzene moiety depending on the number of hydroxy groups,
      the stereochemistry, and the presence of a methyl group in the pyranose ring. A
      fucose-benzene pair is the most stabilizing of the studied series (-0.4 Kcal mol(
      1)) and this interaction can be placed in the same range as other more studied
      interactions with aromatic residues of proteins, such as Phe-Phe, Phe-Met, or Phe
      His. The noncovalent forces involved seem to be dispersion forces and
      nonconventional hydrogen bonds, whereas hydrophobic effects do not seem to drive
      the interaction.

PMID- 18637650
TI  - The basicity of unsaturated hydrocarbons as probed by hydrogen-bond-acceptor
      ability: bifurcated N-H+ ...pi hydrogen bonding.
AB  - The competitive substitution of the anion (A(-)) in contact ion pairs of the type
      [Oct3NH+]B(C6F5)4 (-) by unsaturated hydrocarbons (L) in accordance with the
      equilibrium Oct3NH+...A(-) + nL right arrow over left arrow [Oct3NH+...Ln]A(-)
      has been studied in CCl4. On the basis of equilibrium constants, K, and shifts of
      nuNH to low frequency, it has been established that complexed Oct3NH...+Ln
      cations with n=1 and 2 are formed and have unidentate and bifurcated N--H+...pi
      hydrogen bonds, respectively. Bifurcated hydrogen bonds to unsaturated
      hydrocarbons have not been observed previously. The unsaturated hydrocarbons
      studied include benzene and methylbenzenes, fused-ring aromatics, alkenes,
      conjugated dienes, and alkynes. From the magnitude of the redshifts in the N--H
      stretching frequencies, Delta nuNH, a new scale for ranking the pi basicity of
      unsaturated hydrocarbons is proposed: fused-ring
      aromatics<or=benzene<toluene<xylene<mesitylene<durene<conjugated dienes
      approximately 1-alkynes<pentamethylbenzene<hexamethylbenzene<internal alkynes
      approximately cycloalkenes<1-methylcycloalkenes. This scale is relevant to the
      discussion of pi complexes for incipient protonation reactions and to
      understanding N--H+...pi hydrogen bonding in proteins and molecular crystals.

PMID- 18637652
TI  - Penta(pyrenyl)[60]fullerenes: pyrene-pyrene and [60]fullerene-pyrene interactions
      in the crystal and in solution.
AB  - A new type of fullerene-pyrene hybrid molecule, C(60)Ar(5)R [Ar=1-pyrenyl, 4-(1
      pyrenyl)C(6)H(4), 4-{(1-pyrenyl)CO(2)}C(6)H(4), and 4-{(1
      pyrenyl)(CH(2))(3)CO(2)}C(6)H(4); R=H and Me] was synthesized by a regioselective
      penta-addition reaction using organocopper reagents. The compounds were
      investigated using electrochemical measurements, DFT calculations, single-crystal
      X-ray structural analysis, and spectroscopic and fluorescence measurements.
      Intramolecular and intermolecular fullerene-pyrene and pyrene-pyrene interactions
      were characterized in the crystals. Fluorescence measurements in dilute solutions
      suggested the presence of intramolecular fullerene-pyrene and pyrene-pyrene
      interactions.

PMID- 18637651
TI  - Ruthenium-based olefin metathesis catalysts coordinated with unsymmetrical N
      heterocyclic carbene ligands: synthesis, structure, and catalytic activity.
AB  - A series of ruthenium-based olefin metathesis catalysts coordinated with
      unsymmetrical N-heterocyclic carbene (NHC) ligands has been prepared and fully
      characterized. These complexes are readily accessible in one or two steps from
      commercially available [(PCy(3))(2)Cl(2)Ru==CHPh]. All of the complexes reported
      herein promote the ring-closing of diethyldiallyl and diethylallylmethallyl
      malonate, the ring-opening metathesis polymerization of 1,5-cyclooctadiene, and
      the cross metathesis of allyl benzene with cis-1,4-diacetoxy-2-butene, in some
      cases surpassing in efficiency the existing second-generation catalysts.
      Especially in the cross metathesis of allyl benzene with cis-1,4-diacetoxy-2
      butene, all new catalysts demonstrate similar or higher activity than the second
      generation ruthenium catalysts and, most importantly, afford improved E/Z ratios
      of the desired cross-product at conversion above 60 %. The influence of the
      unsymmetrical NHC ligands on the initiation rate and the activation parameters
      for the irreversible reaction of these ruthenium complexes with butyl vinyl ether
      were also studied. Finally, the synthesis of the related
      chlorodicarbonyl(carbene) rhodium(I) complexes allowed for the study of the
      electronic properties of the new unsymmetrical NHC ligands that are discussed in
      detail.

PMID- 18637653
TI  - Improvement of photoaffinity SPR imaging platform and determination of the
      binding site of p62/SQSTM1 to p38 MAP kinase.
AB  - p38 mitogen-activated protein kinase (MAPK) is a member of the serine/threonine
      kinases and is activated in response to stress stimuli, such as cytokines,
      ultraviolet irradiation, heat shock, and osmotic shock. We revealed in a previous
      report that p62/SQSTM1, known to participate in proteasomal or autophagosomal
      protein degradation and cytokine receptor signal transduction pathways, binds to
      p38 to regulate specifically. Herein, we describe the improvement of the
      photoaffinity-thiol linker of our SPR imaging platform, which enabled us to
      determine the binding site of p62 to p38. SPR imaging experiments using a new
      photoaffinity linker 2 to immobilize the peptides derived from p62 on gold
      substrate indicate that the domain comprising amino acids 164-190 of p62 binds to
      p38 directly. These SPR analysis data and empirical biologic data reveal that the
      binding site of p62 to p38 is the domain corresponding to 173-182.

PMID- 18637654
TI  - Reactions at the Ru-S bonds of coordinatively unsaturated ruthenium complexes
      with tethered 2,6-dimesitylphenyl thiolate.
AB  - Coordinatively unsaturated ruthenium complexes with a tethered SDmp (Dmp=2,6
      dimesitylphenyl) ligand, [(DmpS)Ru(PR(3))][BAr(F) (4)] (3 a: R=Et; 3 b: R=Ph;
      Ar(F)=3,5-(CF(3))(2)C(6)H(3)), were synthesized by the reactions of [{(p
      cymene)RuCl}(2)(mu-Cl)(2)], LiSDmp, phosphines, and NaBAr(F) (4). The Ru--S bonds
      in 3 a and 3 b were found to serve as the polarized reactive site in reactions
      with alkyl halides, diazoalkanes, (p-tosyliminoiodo)benzene, phenylacetylene, and
      H(2). Alkylation of 3 a and 3 b with methyl iodide or ethyl bromide occurred
      instantaneously to give the thioether complexes [(DmpSR')RuX(PR(3))][BAr(F) (4)]
      (4 a: R=Et, R'=Me, X=I; 4 b: R=R'=Et, X=Br; 4 c: R=Ph, R'=Me, X=I; 4 d: R=Ph,
      R'=Et, X=Br). Treatment of 3 a with diazoalkanes N(2)CHR (R=CO(2)Et, SiMe(3)) led
      to the cycloaddition of carbenes to the Ru--S bond to form
      [DmpS(CHR)Ru(PEt(3))][BAr(F) (4)] (5 a: R=CO(2)Et; 5 b: R=SiMe(3)), whereas the
      reaction with (p-tosyliminoiodo)benzene gave rise to [DmpS{NS(O)(C(6)H(4)-4
      CH(3))O}Ru(PEt(3))][BAr(F) (4)] (6), which contains a five-membered ruthenacycle
      of RuSNSO. Addition of phenylacetylene to the Ru--S bond occurred reversibly to
      produce the vinyl sulfide complexes [DmpS(PhCCH)Ru(PR(3))][BAr(F) (4)] (7 a:
      R=Et; 7 b: R=Ph). On the other hand, the phenylacetylene at ruthenium slowly
      isomerized to vinylidene and bridged Ru and S in the products,
      [DmpS{C(CHPh)}Ru(PR(3))][BAr(F) (4)] (8 a: R=Et; 8 b: R=Ph). Complex 3 a
      catalyzed the hydrogenation of acetophenone, in which the heterolytic H-H
      splitting at the Ru-S site is suggested to be involved in the mechanism.

PMID- 18637655
TI  - High-density gold nanoparticles supported on a [Ru(bpy)(3)](2+)-doped
      silica/Fe3O4 nanocomposite: facile preparation, magnetically induced
      immobilization, and applications in ECL detection.
AB  - A large-scale process combined sonication with self-assembly techniques for the
      preparation of high-density gold nanoparticles supported on a [Ru(bpy)(3)](2+)
      doped silica/Fe(3)O(4) nanocomposite (GNRSF) is provided. The obtained hybrid
      nanomaterials containing Fe(3)O(4) spheres have high saturation magnetization,
      which leads to their effective immobilization on the surface of an ITO electrode
      through simple manipulation by an external magnetic field (without the need of a
      special immobilization apparatus). Furthermore, this hybrid nanomaterial film
      exhibits a good and very stable electrochemiluminescence (ECL) behavior, which
      gives a linear response for tripropylamine (TPA) concentrations between 5 muM and
      0.21 mM, with a detection limit in the micromolar range. The sensitivity of this
      ECL sensor can be easily controlled by the amount of [Ru(bpy)(3)](2+) immobilized
      on the hybrid nanomaterials (that is, varying the amount of [Ru(bpy)(3)](2+)
      during GNRSF synthesis).

PMID- 18637656
TI  - Investigations of the growth kinetics of capped CdSe and CdS nanocrystals by a
      combined use of small angle X-ray scattering and other techniques.
AB  - The growth of capped CdSe and CdS nanocrystals formed by the reaction of selenium
      or sulfur with cadmium stearate in toluene solution in the presence of
      dodecanethiol or trioctylphosphine oxide and tetralin, has been investigated by a
      variety of techniques to obtain reliable data. Whereas small angle X-ray
      scattering has provided statistically satisfactory data on the variation of size
      distribution with time, TEM has been used as a direct probe of the particle size,
      although with a limited sampling size. UV/Vis and photoluminescence
      spectroscopies have also provided information about the time evolution of the
      average diameter (D) of the nanocrystals. By employing all these techniques, we
      have obtained the D(t) data and fitted then to various growth models. Although
      certain qualitative observations suggest growth of the nanocrystals to be
      controlled by diffusion-limited Ostwald ripening, we have found it is necessary
      to include the surface reaction term in the growth equation. Thus, the growth of
      CdSe and CdS nanocrystals has contributions from both diffusion and surface
      reaction, with a D(3)+D(2) type behavior, independent of the capping agent.

PMID- 18637657
TI  - Cationic scandium allyl complexes bearing mono(cyclopentadienyl) ligands:
      synthesis, novel structural variety, and olefin-polymerization catalysis.
AB  - The one-pot salt-metathesis reaction of ScCl(3), cyclopentadienyl lithium salts,
      and allylmagnesium chlorides afforded with ease the corresponding base-free half
      sandwich scandium di(eta(3)-allyl) complexes [(C(5)Me(4)SiMe(3))Sc(C(3)H(5))(2)]
      (1 a), [(C(5)Me(5))Sc(C(3)H(5))(2)] (1 b), and [(C(5)Me(5))Sc(2-MeC(3)H(4))(2)]
      (1 c) in high yields. Reaction of 1 a with 1 equivalent of
      [PhNMe(2)H][B(C(6)F(5))(4)] in toluene gave rapidly the N,N-dimethylaniline
      coordinated cationic mono(eta(3)-allyl) complex [(C(5)Me(4)SiMe(3))Sc(eta(3)
      C(3)H(5))(eta(6)-PhNMe(2))][B(C(6)F(5))(4)] (2). The similar reaction of 1 a with
      [Ph(3)C][B(C(6)F(5))(4)] yielded the analogous toluene-separated ion pair
      [(C(5)Me(4)SiMe(3))Sc(eta(3)-C(3)H(5))(eta(6)-PhMe)][B(C(6)F(5))(4)] (3). When
      [PhNMe(2)H][BPh(4)] was treated with 1 a, the contact ion pair
      [(C(5)Me(4)SiMe(3))Sc(eta(3)-C(3)H(5))( mu,eta(6)-Ph)BPh(3)] (4) was obtained.
      Recrystallization of 2, 3, and 4 in THF yielded the corresponding thf-separated
      ion pair complexes [(C(5)Me(4)SiMe(3))Sc(eta(3)
      C(3)H(5))(thf)(2)][B(C(6)F(5))(4)] (5) and [(C(5)Me(4)SiMe(3))Sc(eta(3)
      C(3)H(5))(thf)(2)][BPh(4)] (6). The N,N-dimethylaniline-coordinated cationic
      scandium allyl complex 2 and the toluene-coordinated analogue 3 showed high
      activity (activity: 3>2) toward the polymerization and copolymerization of
      isoprene and norbornene to afford random copolymers with a broad range of
      isoprene content (33-86 mol %). The tight ion pair 4 and the thf-coordinated
      complexes 5 and 6 showed no activity under the same conditions. These results
      offer unprecedented insight into the structure-activity relationship of a
      cationic metal polymerization-catalyst system.

PMID- 18637658
TI  - Solphos: a new family of efficient biaryl diphosphine ligands.
AB  - Solphos (7,7'-bis(diarylphosphino)-3,3',4,4'-tetrahydro-4,4'-dimethyl-8,8'-bis-2H
      1,4-benzoxazine) is a new modular atropisomeric biaryl ligand with a very
      attractive activity profile. A technically feasible synthesis is described
      allowing the synthesis of various derivatives of enantiopure ligand on a
      technical scale. Very good catalytic performances have been demonstrated for the
      following transformations: Ru-catalyzed hydrogenation of various beta-keto esters
      (95-99 % ee, s/c up to 100,000), of acetyl acetone (>99 % ee, dl/meso>98:2), and
      of an exocyclic alpha,beta-unsaturated acid (98.6 % ee, s/c 250). In several
      cases, the nature of the PAr(2) moiety had a significant effect on the
      enantioselectivity. Furthermore, Rh and Ir Solphos complexes achieved high
      enantioselectivities for a novel synthesis of 3,3-disubstituted phthalides and
      the reductive coupling of alkynes with N-sulfonyl imines, respectively.

PMID- 18637659
TI  - Crystalline degradation products of vancomycin as chiral stationary phase in
      microcolumn liquid chromatography.
AB  - The ability of crystalline degradation products (CDPs) of vancomycin as a chiral
      stationary phase was reported in a previous study for enantioselective separation
      of drugs, amino acids and agrochemical toxins by conventional LC column (250 x
      4.6 mm). In this work, the potential of CDP of vancomycin for the enantiomeric
      separation in micro-LC (200 x 1 mm) has been studied. The obtained separation
      results are better than in our previous study with conventional LC columns. The
      enantiomers of D,L-phenylalanine, D,L-alanine, methyldopa, atropine and
      propranolol were used for this evaluation. Experiments have been carried out in a
      stainless steel tube that was packed with chiral silica particles of 3 and 12
      microm diameters. Also, three different ratios of 3 and 12 microm silica
      particles were used for packing material of chiral columns and the effect on
      aspect ratio and resolving powers was compared.

PMID- 18637660
TI  - Free-radical destruction of beta-lactam antibiotics in aqueous solution.
AB  - Many pharmaceutical compounds and metabolites are being found in surface and
      ground waters, indicating their ineffective removal by conventional wastewater
      treatment technologies. Advanced oxidation/reduction processes (AO/RPs), which
      utilize free-radical reactions to directly degrade chemical contaminants, are
      alternatives to traditional water treatment. This study reports the absolute rate
      constants for reaction of three beta-lactam antibiotics (penicillin G, penicillin
      V, amoxicillin) and a model compound (+)-6-aminopenicillanic acid with the two
      major AO/RP reactive species: hydroxyl radical ((*)OH) and hydrated electron (e(
      )aq). The bimolecular reaction rate constants (M(-1) s(-1)) for penicillin G,
      penicillin V, amoxicillin, and (+)-6-aminopenicillanic acid for (*)OH were (7.97
      +/- 0.11) x 10(9), (8.76 +/- 0.28) x 10(9), (6.94 +/- 0.44) x 10(9), and (2.40 +/
      0.05) x 10(9) and for e(-)aq were (3.92 +/- 0.10) x 10(9), (5.76 +/- 0.24) x
      10(9), (3.47 +/- 0.07) x 10(9), and (3.35 +/- 0.06) x 10(9), respectively. To
      provide a better understanding of the decomposition of the intermediate radicals
      produced by hydroxyl radical reactions, transient absorption spectra were
      observed from 1 to 100 micros. In addition, preliminary degradation mechanisms
      and major products were elucidated using (137)Cs gamma irradiation and LC-MS.
      These data are required for both evaluating the potential use of AO/RPs for the
      destruction of these compounds and studies of their fate and transport in surface
      waters where radical chemistry may be important in assessing their lifetime.

PMID- 18637661
TI  - Site-dependent spectral shifts in core-to-pi* excitations of pyridine clusters.
AB  - Site- and element-selective core-to-pi* excitation in free pyridine clusters is
      investigated. The experimental results indicate the occurrence of site- and size
      dependent spectral shifts in the C 1s and N 1s --> pi* excitation regime.
      Specifically, we observe in the C 1s regime a substantial and site-dependent
      redshift of the low energy slopes of the C 1s --> pi* band by 90 meV in clusters
      relative to the bare molecule, whereas the high energy slopes of this band remain
      almost unchanged. In contrast, a size-dependent blueshift of the same order of
      magnitude is found for the entire N 1s --> pi* band. This is distinctly different
      from previous results on van der Waals clusters, where exclusively redshifts in
      1s --> pi* transitions are observed. The experimental results are compared to ab
      initio calculations, which serve to simulate the 1s --> pi*( v = 0) transitions.
      These results clearly indicate that the spectral shifts are primarily a result of
      electrostatic interactions between the molecular moieties and that an
      antiparallel orientation of molecular units preferably dominates in variable-size
      pyridine clusters.

PMID- 18637662
TI  - Microwave spectrum, conformation and intramolecular hydrogen bonding of 2,2,2
      trifluoroethanethiol (CF3CH2SH).
AB  - The microwave spectrum of 2,2,2-trifluoroethanethiol, CF3CH2SH, and of one
      deuterated species, CF3CH2SD, has been investigated in the 7-80 GHz spectral
      interval. The microwave spectra of the ground and three vibrationally excited
      states belonging to three different normal modes of one conformer were assigned
      for the parent species, and the vibrational frequencies of these fundamentals
      were determined by relative intensity measurements. Only the ground vibrational
      state was assigned for the deuterated species. The identified form has a
      synclinal arrangement for the H-S-C-C chain of atoms and the corresponding
      dihedral angle is 68(5) degrees from synperiplanar (0 degrees). A weak
      intramolecular hydrogen bond formed between the thiol (SH) group and one of the
      fluorine atoms is stabilizing this conformer. There is no evidence in the
      microwave spectrum for the H-S-C-C antiperiplanar form. The hydrogen atom of the
      thiol group should have the ability to tunnel between two equivalent synclinal
      potential wells, but no splittings of spectral lines due to tunneling were
      observed. The microwave work was augmented by quantum chemical calculations at
      the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVTZ levels of theory.

PMID- 18637663
TI  - Origins of stereoselectivity in the Diels-Alder addition of chiral hydroxyalkyl
      vinyl ketones to cyclopentadiene: a quantitative computational study.
AB  - Modest basis set level MP2/6-31G(d,p) calculations on the Diels-Alder addition of
      S-1-alkyl-1-hydroxy-but-3-en-2-ones (1-hydroxy-1-alkyl methyl vinyl ketones) to
      cyclopentadiene correctly reproduce the trends in known experimental endo/exo and
      diastereoface selectivity. B3LYP theoretical results at the same or significantly
      higher basis set level, on the other hand, do not satisfactorily model observed
      endo/exo selectivities and are thus unsuitable for quantitative studies. The same
      is valid also with regard to subtle effects originating from, for example,
      conformational distributions of reactants. The latter shortcomings are not
      alleviated by the fact that observed diastereoface selectivities are well
      reproduced by DFT calculations. Quantitative computational studies of large
      cycloaddition systems would require higher basis sets and better account for
      electron correlation than MP2, such as, for example, CCSD. Presently, however,
      with 30 or more non-hydrogen atoms, these computations are hardly feasible. We
      present quantitatively correct stereochemical predictions using a hybrid layered
      ONIOM computational approach, including the chiral carbon atom and the
      intramolecular hydrogen bond into a higher level, MP2/6-311G(d,p) or CCSD/6
      311G(d,p), layer. Significant computational economy is achieved by taking account
      of surrounding bulky (alkyl) residues at 6-31G(d) in a low HF theoretical level
      layer. We conclude that theoretical calculations based on explicit correlated MO
      treatment of the reaction site are sufficiently reliable for the prediction of
      both endo/exo and diastereoface selectivity of Diels-Alder addition reactions.
      This is in line with the understanding of endo/exo selectivity originating from
      dynamic electron correlation effects of interacting pi fragments and
      diastereofacial selectivity originating from steric interactions of fragments
      outside of the Diels-Alder reaction site.

PMID- 18637664
TI  - Dynamics of vibrational overtone excited pyruvic acid in the gas phase: line
      broadening through hydrogen-atom chattering.
AB  - The dynamics of overtone-excited pyruvic acid (PA) is studied using a combination
      of experimental and theoretical methods. It is experimentally observed that high
      overtone excitation of the OH-stretching mode of PA in the gas phase leads to a
      unimolecular decarboxylation reaction. An RRKM analysis of the rate is consistent
      with previous experiments for the thermal reaction but is inconsistent with the
      present overtone chemistry; from this it is concluded that the overtone-induced
      reaction is likely to be a direct reaction. Using a Fourier transform infrared
      spectrometer and a cavity ring-down spectrometer, the spectrum for the OH-stretch
      fundamental and overtone transitions is measured. We assign two conformers of PA
      in the spectrum, the Tc and Tt, corresponding to distinct orientations of the OH
      group. The spectral peaks for the Tc-conformer broaden dramatically at the third
      and fourth overtones while those of the Tt-conformer remain relatively narrow.
      Using a three-mode quantum mechanical model for the vibrational states, the line
      positions and intensities are well reproduced by theory. The line widths, and the
      associated dynamical interpretation, are provided by a direct dynamics
      calculation, where the potential is computed "on-the-fly" and all degrees of
      freedom are included. It is found that the line broadening is due to the onset of
      H-atom chattering between the two O-atoms, an effect that occurs for the Tc
      conformer but not the Tt-conformer. This H-atom-transfer process is the first
      step of the decarboxylation reaction mechanism, which subsequently involves
      breaking the C-C bond. The theoretical and experimental line widths agree but do
      not correspond to the full reaction time which is much longer than the initial
      chattering step.

PMID- 18637665
TI  - Electrodecomposition in subcritical water using o-xylene as a model for benzene,
      toluene, ethylbenzene, and xylene pollutants.
AB  - The possibility of the combination of electrolysis and subcritical water as a
      novel electrolyte was investigated. A stainless steel reactor was used as an
      undivided electrochemical cell containing platinum as the anode and a stainless
      steel reactor as the cathode. At first, the effect of temperature on the
      electrolysis current as the main parameter was studied in a cell containing only
      pure water and a supporting electrolyte. It was realized that the electrolysis
      current (and, consequently, the electrolysis efficiency) increased linearly with
      temperature because of the change in viscosity and other physicochemical
      properties of subcritical water. As a result, at 553 K the electrolysis
      efficiency was over 14-fold higher than that under ambient conditions. The
      possibility of the applicability of the above combined techniques for the
      decomposition of o-xylene was also followed as a model for benzene, toluene,
      ethylbenzene, and xylene (BTEX) compounds. The effect of experimental conditions
      such as the electrolysis duration, the electrolysis voltage, and the temperature
      of subcritical water was investigated. Several decomposed products were
      identified. o-Xylene was directly electro-oxidized to 2-methylbenzyl alcohol and
      consecutively to the other oxidation products. Also, hydroxide ions were oxidized
      to oxygen molecules, where hydrogen was generated on the cathodic surface. The
      final oxidation product of the electro-oxidation reaction was identified as
      carbon dioxide. The results indicate that more than 95% of o-xylene can be
      decomposed under optimum conditions.

PMID- 18637666
TI  - Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P.
      falciparum strains that also inhibit botulinum serotype A.
AB  - We report on the initial result of the coupling of 4-amino-7-chloroquinoline with
      steroidal and adamantane constituents to provide small molecules with excellent
      in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities
      also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at
      low micromolar levels (7-31 microM). Interestingly, structural features imparting
      increased antimalarial activity also provide increased metalloprotease
      inhibition, thus allowing for simultaneous compound optimizations against
      distinct targets.

PMID- 18637667
TI  - Novel analogues of istaroxime, a potent inhibitor of Na+,K+-ATPase: synthesis and
      structure-activity relationship.
AB  - We report the synthesis and biological properties of novel inhibitors of the
      Na(+),K(+)-ATPase as positive inotropic compounds. Following our previously
      described model from which Istaroxime was generated, the 5alpha,14alpha
      androstane skeleton was used as a scaffold to study the space around the basic
      chain of our lead compound. Some compounds demonstrated higher potencies than
      Istaroxime on the receptor and the (E)-3-[(R)-3-pyrrolidinyl]oxime derivative,
      15, was the most potent; as further confirmation of our model, the E isomers of
      the oxime are more potent than the Z form. The compounds tested in the guinea pig
      model induced positive inotropic effects, which are correlated to the in vitro
      inhibitory potency on the Na(+),K(+)-ATPase. The finding that all tested
      compounds resulted less proarrhythmogenic than digoxin, a currently clinically
      used positive inotropic agent, suggests that this could be a feature of the 3
      aminoalkyloxime derivative class of 5alpha,14alpha-androstane.

PMID- 18637668
TI  - (9S)-9-(2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-2,3,4,9
      tetrahydro-1H-xanthen-1-one, a selective and orally active neuropeptide Y Y5
      receptor antagonist.
AB  - (9S)-9-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-2,3,4,9
      tetrahydro-1H-xanthen-1-one ((S)-1) was identified as a selective and orally
      active neuropeptide Y Y5 receptor antagonist. The structure-activity relationship
      for this structural class was investigated and showed that limited substitution
      on the phenyl ring was tolerated and that modification of the 4,4-dimethyl group
      of the cyclohexenone and the 3,3-dimethyl group of the xanthenone parts slightly
      improved potency. The plasma concentration-time profile after oral administration
      of (S)-1 in Sprague-Dawley (SD) rats showed significant in vivo racemization of
      (S)-1 and that (S)-1 is cleared much more quickly than (R)-1. The duration of (S)
      1 in SD rats after oral administration of (RS)-1 racemate was twice as long as
      that following oral administration of (S)-1. The C max values of (S)-1 after
      administration of (S)-1 and (RS)-1 were comparable, and the brain to plasma ratio
      for (S)-1 was 0.34 in SD rats. In our acute D-Trp (34)NPY-induced food intake
      model, both (S)-1 and (RS)-1 showed potent and dose-dependent efficacy.
      Therefore, the use of (RS)-1 is suitable for studies that require sustained
      plasma exposure of (S)-1.

PMID- 18637669
TI  - Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the
      prostate-specific membrane antigen (PSMA).
AB  - The prostate-specific membrane antigen (PSMA) is increasingly recognized as a
      viable target for imaging and therapy of cancer. We prepared seven (99m)Tc/Re
      labeled compounds by attaching known Tc/Re chelating agents to an amino
      functionalized PSMA inhibitor (lys-NHCONH-glu) with or without a variable length
      linker moiety. K i values ranged from 0.17 to 199 nM. Ex vivo biodistribution and
      in vivo imaging demonstrated the degree of specific binding to engineered PSMA+
      PC3 PIP tumors. PC3-PIP cells are derived from PC3 that have been transduced with
      the gene for PSMA. Despite demonstrating nearly the lowest PSMA inhibitory
      potency of this series, [(99m)Tc(CO)3( L1)] (+) ( L1 = (2-pyridylmethyl)2N(CH2)
      4CH(CO2H)NHCO-(CH2) 6CO-NH-lys-NHCONH-glu) showed the highest, most selective PIP
      tumor uptake, at 7.9 +/- 4.0% injected dose per gram of tissue at 30 min
      postinjection. Radioactivity cleared from nontarget tissues to produce a PIP to
      flu (PSMA-PC3) ratio of 44:1 at 120 min postinjection. PSMA can accommodate the
      steric requirements of (99m)Tc/Re complexes within PSMA inhibitors, the best
      results achieved with a linker moiety between the epsilon amine of the urea
      lysine and the chelator.

PMID- 18637670
TI  - 2-Amino-6-furan-2-yl-4-substituted nicotinonitriles as A2A adenosine receptor
      antagonists.
AB  - A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic
      systems with varying substitution patterns to achieve desired receptor affinity
      and selectivity. Using a pharmacophore model designed by overlap of nonxanthine
      type of previously known A 2A antagonists, we synthesized a new class of
      compounds having a 2-amino nicotinonitrile core moiety. From our data, we
      conclude that the presence of at least one furan group rather than phenyl is
      beneficial for high affinity on the A 2A adenosine receptor. Compounds 39
      (LUF6050) and 44 (LUF6080) of the series had K i values of 1.4 and 1.0 nM,
      respectively, with reasonable selectivity toward the other adenosine receptor
      subtypes, A 1, A 2B, and A 3. The high affinity of 44 was corroborated in a cAMP
      second messenger assay, yielding subnanomolar potency for this compound.

PMID- 18637671
TI  - Structure-antitussive activity relationships of naltrindole derivatives.
      Identification of novel and potent antitussive agents.
AB  - We have previously reported antitussive effects of naltrindole (NTI), a typical
      delta opioid receptor antagonist, in a rat model. The ED50 values of NTI by
      intraperitoneal and peroral injections were 104 microg/kg and 1840 microg/kg,
      respectively, comparable to those of codeine. Codeine, one of the most reliable
      centrally acting antitussive drugs, has micro agonist activity and thus the same
      side effects as morphine, e.g., constipation, dependency, and respiratory
      depression. Because NTI is a delta opioid antagonist, its derivatives have
      potential as highly potent antitussives, free from the mu opioid agonist side
      effects. We attempted to optimize the NTI derivatives to develop novel
      antitussive agents. On the basis of the studies of structure-antitussive activity
      relationships of alkyl substituted NTI derivatives, we designed NTI derivatives
      with extra ring fused structures. As a clinical candidate, we identified a highly
      potent new compound, (5R,9R,13S,14S)-17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy
      5',6'-dihydro-3-methoxy-4'H-pyrrolo[3,2,1-ij]quinolino[2',1':6,7]morphinan-14-ol
      (5b) methanesulfonate (TRK-850) which was effective even by oral administration
      (ED50 6.40 microg/kg).

PMID- 18637672
TI  - Ethyl 8-fluoro-6-(3-nitrophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3
      carboxylate as novel, highly potent, and safe antianxiety agent.
AB  - Ethyl 8-fluoro-6-(4-nitrophenyl)- and ethyl 8-fluoro-6-(3-nitrophenyl)-4 H
      imidazo[1,5-a][1,4]benzodiazepine 3-carboxylate 6 and 7 were synthesized as
      central benzodiazepine receptor (CBR) ligands and tested for their ability to
      displace [(3)H]flumazenil from bovine and human cortical brain membranes. Both
      compounds showed high affinity for bovine and human CBR. In particular, compound
      7 emerged as the most interesting compound, having a partial agonist profile in
      vitro while possessing useful activity in various animal models of anxiety. In
      accordance with its partial agonist profile, compound 7 was devoid of typical
      benzodiazepine side effects. The homology model of the GABA A receptor developed
      by Cromer et al. was used to assess the binding modes of ligands 6 and 7. From
      our docking results, the partial agonist activity elicited by compound 7 is
      likely to be due to the 3'-nitro substituent, which is in the appropriate
      position to interact with Thr193 of the gamma 2-subunit by means of a hydrogen
      bond.

PMID- 18637673
TI  - Evolving interpretable structure-activity relationship models. 2. Using
      multiobjective optimization to derive multiple models.
AB  - A multiobjective evolutionary algorithm (MOEA) is described for evolving multiple
      structure-activity relationships (SARs). The SARs are encoded in easy-to
      interpret reduced graph queries which describe features that are preferentially
      present in active compounds compared to inactives. The MOEA addresses a
      limitation associated with many machine learning methods; that is, the inherent
      tradeoff that exists in recall and precision which is usually handled by
      combining the two objectives into a single measure with a consequent loss of
      control. By simultaneously optimizing recall and precision, the MOEA generates a
      family of SARs that lie on the precision-recall (PR) curve. The user is then able
      to select a query with an appropriate balance in the two objectives: for example,
      a low recall-high precision query may be preferred when establishing the SAR,
      whereas a high recall-low precision query may be more appropriate in a virtual
      screening context. Each query on the PR curve aims at capturing the structure
      activity information into a single representation, and each can be considered as
      an alternative (equally valid) solution. We then investigate combining individual
      queries into teams with the aim of capturing multiple SARs that may exist in a
      data set, for example, as is commonly seen in high-throughput screening data
      sets. Team formation is carried out iteratively as a postprocessing step
      following the evolution of the individual queries. The inclusion of uniqueness as
      a third objective within the MOEA provides an effective way of ensuring the
      queries are complementary in the active compounds they describe. Substantial
      improvements in both recall and precision are seen for some data sets.
      Furthermore, the resulting queries provide more detailed structure-activity
      information than is present in a single query.

PMID- 18637674
TI  - Discovery of novel cathepsin S inhibitors by pharmacophore-based virtual high
      throughput screening.
AB  - The cysteine protease cathepsin S (CatS) is involved in the pathogenesis of
      autoimmune disorders, atherosclerosis, and obesity. Therefore, it represents a
      promising pharmacological target for drug development. We generated ligand-based
      and structure-based pharmacophore models for noncovalent and covalent CatS
      inhibitors to perform virtual high-throughput screening of chemical databases in
      order to discover novel scaffolds for CatS inhibitors. An in vitro evaluation of
      the resulting 15 structures revealed seven CatS inhibitors with kinetic constants
      in the low micromolar range. These compounds can be subjected to further chemical
      modifications to obtain drugs for the treatment of autoimmune disorders and
      atherosclerosis.

PMID- 18637675
TI  - Silanol-based pincer Pt(II) complexes: synthesis, structure, and unusual
      reactivity.
AB  - Aiming at the generation of a silanone intramolecularly bound to platinum, we
      prepared pincer-type PSiP silanol Pt(II) complexes. While a stable silanone
      complex was not isolated, unusual reactivity modes, involving its possible
      intermediacy, were observed. Treatment of the new PSiH 2P-type ligand ( o-IPr 2PC
      6H 4) 2SiH 2 ( 7) with (Me 2S) 2Pt(Me)Cl yields the pincer-type hydrosilane
      complex [{( o- iPr 2PC 6H 4) 2SiH}PtCl] ( 8), which upon Ir(I)-catalyzed
      hydrolytic oxidation gives the structurally characterized silanol complex [{( o-
      iPr 2PC 6H 4) 2SiOH}PtCl] ( 3). Complex 3, comprising in its structure the
      nucleophilic silanol fragment and electrophilic Pt(II)-Cl moiety, exhibits dual
      reactivity. Its reaction with the non-nucleophilic KB(C 6F 5) 4 in fluorobenzene
      leads to the ionic complex [{( o- iPr 2PC 6H 4) 2SiOH}Pt] (+) [(C 6F 5) 4B] (-) (
      9), which reacts with CO to yield the structurally characterized [{( o- iPr 2PC
      6H 4) 2SiOH}PtCO] (+) [(C 6F 5) 4B] (-) ( 10). Treatment of 3 with non
      nucleophilic bases leads to unprecedented rearrangement and coupling, resulting
      in the structurally characterized, unusual binuclear complex 11. The structure of
      11 comprises two different fragments: the original O-Si-Pt(II)-Cl pattern, and
      the newly formed silanolate Pt(II)-H pattern, which are connected via a
      disiloxane bridge. Complex 9 undergoes a similar hydrolytic rearrangement in the
      presence of iPr 2NEt to give the mononuclear silanolate Pt(II)-H complex 17. Both
      these rearrangement-coupling reactions probably involve the inner-sphere
      generation of an intermediate silanone 14, which undergoes nucleophilic attack by
      the starting silanol 3 to yield complex 11, or adds a water molecule to yield
      complex 17. X-ray diffraction studies of 3, 10, and 11 exhibit a very short Si-Pt
      bond length (2.27-2.28 A) in the neutral complexes 3 and 11 that elongates to
      2.365 A in the carbonyl complex 10. A significantly compressed geometry of the
      silanolate platinum(II)-hydride fragment B of the binuclear complex 11 features a
      Pt(2)-O(2)-Si(2) angle of 100.4 (3) degrees and a remarkably short Pt(2)...Si(2)
      [2.884 (3) A] distance.

PMID- 18637676
TI  - Solid state and aqueous solution characterization of rectangular tetranuclear
      V(IV/V)-p-semiquinonate/hydroquinonate complexes exhibiting a proton induced
      electron transfer.
AB  - Reaction of the non-innocent dinucleating ligand 2,5-bis[N,N-bis(carboxymethyl)
      aminomethyl]hydroquinone (H 6bicah) with VO (2+) and VO 4 (3-) salts in water in
      the pH range 2 to 4.5 provides a series of novel tetranuclear V (IV) and/or V (V)
      macrocycles with the main core consisting of the anions [V (V) 4O 4(mu-O) 2(mu
      bicah) 2] (4-) isolated at pH = 2.5 and [V (IV) 2V (V) 2O 4(mu-O) 2(mu-bicas)(mu
      bicah)] (5-) and [V (IV) 4O 4(mu-O) 2(mu-bicas) 2] (6-) isolated at pH = 4.5
      (bicas (*5-) = 2,5-bis[N,N-bis(carboxymethyl) aminomethyl]- p-semiquinonate),
      whereas at pH = 2 the dinuclear [(V (IV)O) 2(OH 2) 2(mu-bicah)] (2-) was
      obtained. All vanadium compounds have been characterized, and the charge of the
      ligand has been assigned in solid state by X-ray crystallography and infrared
      spectroscopy. The structures of the tetranuclear anions consist of four vanadium
      atoms arranged at the corners of a rectangle with the two bridging bicas (*5-)
      and/or bicah (6-) ligands on the long and the two V (IV/V)-O-V (IV/V) bridges on
      the short sides of the rectangle. UV-vis, (51)V and (1)H NMR spectroscopy and
      electrochemistry showed that these complexes interconvert to each other by
      varying the pH. This pH induced redox transformation of the tetranuclear anions
      has been attributed to the shift of the reduction potential of the bicas (*5-) to
      higher values by decreasing the pH. The electron is transferred intramolecularly
      from the metal ion to the electron accepting semiquinones resulting in reduction
      of bicas (*5-) to bicah (6-) and concurrent oxidation of the V (IV) to V (V). The
      resulting complexes are further oxidized by atmospheric oxygen. This system as a
      model for the H (+) coupled redox reactions in metalloenzymes and its relevance
      is discussed briefly.

PMID- 18637677
TI  - BX4- and AlX4- superhalogen anions (X = F, Cl, Br): an ab initio study.
AB  - The vertical electron detachment energies (VDEs) of 30 MX 4 (-) (M = B, Al; X =
      F, Cl, Br) anions were calculated at the OVGF level with the 6-311+G(3df) basis
      sets. The largest vertical electron binding energy was found for the AlF 4 (-)
      system (9.789 eV). The strong VDE dependence on the symmetry of the species,
      ligand type, ligand-central atom distance, and bonding/nonbonding/antibonding
      character of the highest occupied molecular orbital was observed and discussed.

PMID- 18637678
TI  - Assembly of silver(I)-organic networks from flexible supramolecular synthons with
      pendant ethynide arms attached to a naphthyl skeleton.
AB  - Five new ligands bearing terminal ethynide moieties attached via pendant arms to
      a naphthyl skeleton have been used in the synthesis of eight silver(I) complexes.
      In these compounds, the invariable appearance of the mu 4 and mu 5 ligation modes
      of the ethynide moiety reaffirms the general utility of the silver-ethynide
      supramolecular synthons R-CC supersetAg n and Ag n subsetCC-R-CC supersetAg n ( n
      = 4, 5) in coordination network assembly, even when the R group is
      conformationally flexible. Besides the silver-ethynyl and silver-aromatic
      interactions, several unconventional intermolecular interactions
      (argentophilicity, anion-pi, C-H...pi, and CN...pi) also make their appearance.

PMID- 18637679
TI  - Highly sensitive multiresponsive chemosensor for selective detection of Hg2+ in
      natural water and different monitoring environments.
AB  - A new chemosensor RF1 that combines a ferrocene unit and a rhodamine block via
      the linkage of a carbohydrazone binding unit was designed and prepared for the
      highly selective detection of Hg (2+) in natural water. This chemosensor displays
      great brightness and fluorescence enhancement following Hg (2+) coordination
      within the limit of detection for Hg (2+) at 1 parts per billion (ppb). The
      fluorescence intensities are nearly proportional to the amount of Hg (2+) at the
      ppb level. It is capable of distinguishing between the safe and the toxic levels
      of inorganic mercury in drinking water. Hg (2+)-binding also arouses the
      absorption of the rhodamine moiety in RF1 significantly with the chromogenic
      detection limit for Hg (2+) at 50 ppb. The conventional UV-vis spectroscopic
      method thus has the potential to provide the critical information about the
      mercury hazard assessment for industrial wastewater discharging. The obvious and
      characteristic color change of the titration solution from colorless to pink upon
      the addition of Hg (2+) demonstrates that RF1 can be used for "naked-eye"
      detection of Hg (2+) in water. The Hg (2+) complexation also causes a significant
      shift of the redox potential about the ferrocene/ferrocenium couple. The
      electrochemical responses provide the possibility to quantitative analysis of Hg
      (2+) at the parts per million (ppm) level. Preliminary investigations in natural
      water samples including seawater and freshwater indicate that RF1 offers a direct
      and immediate Hg (2+) detection in complex media, pointing out its potential
      utility in environment monitoring and assessment. The responses of RF1 are Hg
      (2+) specific, and the chemosensor exhibits high selectivity toward Hg (2+) over
      other Group 12 metals, alkali, alkaline earth metals, and most of the divalent
      first-row transition metals. The RF1-Hg (2+) complex is successfully isolated and
      the Hg (2+)-binding is reversible. The crystal structure and spectral properties
      of its congener RF2 that contains one ferrocene group and two rhodamine 6G
      moieties were also investigated for a comparison.

PMID- 18637680
TI  - Anti-CD22-MCC-DM1 and MC-MMAF conjugates: impact of assay format on
      pharmacokinetic parameters determination.
AB  - CD22 represents a promising target for antibody-drug conjugate therapy in the
      context of B cell malignancies since it rapidly internalizes, importing
      specifically bound antibodies with it. To determine the pharmacokinetic
      parameters of anti-CD22-MCC-DM1 and MC-MMAF conjugates, various approaches to
      quantifying total and conjugated antibody were investigated. Although the total
      antibody assay formats gave similar results for both conjugates, the mouse
      pharmacokinetic profile for the anti-CD22-MCC-DM1 and MC-MMAF appeared
      significantly different depending on the conjugated antibody assay format. Since
      these differences significantly impacted the PK parameters determination, we
      investigated the effect of the drug/antibody ratio on the total and conjugated
      antibody quantification using multiple assay formats. Our investigations revealed
      the limitations of some assay formats to quantify anti-CD22-MCC-DM1 and MC-MMAF
      with different drug load and in the context of a heterogeneous ADC population
      highlight the need to carefully plan the assay strategy for the total and
      conjugated antibody quantification in order to accurately determine the ADC PK
      parameters.

PMID- 18637681
TI  - Docking and molecular dynamics study on the inhibitory activity of coumarins on
      aldose reductase.
AB  - In order to explore the inhibitory mechanism of coumarins toward aldose reductase
      (ALR2), AutoDock and Gromacs software were used for docking and molecular
      dynamics studies on 14 coumarins (CM) and ALR2 protease. The docking results
      indicate that residues TYR48, HIS110, and TRP111 construct the active pocket of
      ALR2 and, besides van der Waals and hydrophobic interaction, CM mainly interact
      with ALR2 by forming hydrogen bonds to cause inhibitory behavior. Except for CM1,
      all the other coumarins take the lactone part as acceptor to build up the
      hydrogen bond network with active-pocket residues. Unlike CM3, which has two
      comparable binding modes with ALR2, most coumarins only have one dominant
      orientation in their binding sites. The molecular dynamics calculation, based on
      the docking results, implies that the orientations of CM in the active pocket
      show different stabilities. Orientation of CM1 and CM3a take an unstable binding
      mode with ALR2; their conformations and RMSDs relative to ALR2 change a lot with
      the dynamic process. While the remaining CM are always hydrogen-bonded with
      residues TYR48 and HIS110 through the carbonyl O atom of the lactone group during
      the whole process, they retain the original binding mode and gradually reach
      dynamic equilibrium.

PMID- 18637682
TI  - pH-responsive nanoaggregation of diblock phosphorylcholine copolymers.
AB  - We have characterized three diblock copolymers bearing zwitterionic
      phosphorylcholine and weak tertiary amine groups, namely, poly[((2
      (methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(dimethylamino)ethyl
      methacrylate)60] (denoted as MPC30-DMA60, Mn=18,000), poly[((2
      (methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(diethylamino)ethyl
      methacrylate)60) (denoted as MPC30-DEA60, Mn=20,000), and poly[((2
      (methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(diisopropylamino)ethyl
      methacrylate)60) (denoted as MPC30-DPA60, Mn=21,000), by studying their surface
      tension and solution aggregation through a combined approach of surface tension
      measurement, dynamic light scattering, and small-angle neutron scattering. Our
      results show that larger tertiary amine substituents lead to an increasing
      tendency to form micellar aggregates, which is consistent with the increasing
      copolymer hydrophobicity. Thus, MPC30-DMA60 did not aggregate under the
      experimental conditions studied. The free chains exist in the form of thin
      cylinders, whose length decreases with copolymer concentration and solution
      temperature but increases with solution pH. The diameters of the MPC30-DMA60
      cylinders remained almost constant at around 30 A under all the conditions
      studied. At the lower copolymer concentration of 0.5 wt %, the cylindrical
      lengths correspond to the persistence length of the copolymer backbone and are
      close to its full length, indicating a rather high rigidity. Further data
      analysis showed that, at the two higher concentrations of 2 and 4 wt %, the
      phosphorylcholine and amine blocks associate, inducing bending of the copolymer
      backbone. One backbone kink was required to satisfy all the constraints,
      including the dry volume of the copolymer. MPC30-DEA60 showed a similar trend of
      pH- and concentration-dependent conformational responses for the free copolymer,
      but in addition micellar aggregation occurred at pH 9. In contrast, MPC30-DPA60
      exhibited significantly reduced solubility associated with strong aggregation,
      which is consistent with it being the most hydrophobic copolymer in the series.

PMID- 18637683
TI  - Classical and quantum gibbs free energies and phase behavior of water using
      simulation and cell theory.
AB  - A method to calculate the classical and quantum free energy of a liquid from a
      computer simulation by using cell theory [J. Chem. Phys. 2007, 126, 064504] is
      tested for liquid water and ice Ih against experiment as a function of
      temperature. This fast and efficient method reproduces reasonably well the
      experimental values of entropy, enthalpy, and free energy of a liquid across the
      supercooled, stable, and superheated range of temperatures considered. There are
      small differences between classical and quantum results of water at 298 K,
      necessitating a small correction term to reproduce water's enthalpy of
      vaporisation. Only at higher temperatures is entropy underestimated by up to 9 J
      K(-1) mol(-1) as verified by thermodynamic integration calculations. Satisfactory
      agreement for ice, however, is only obtained by using the quantum formulation.
      Even then, at higher temperatures, the entropies exceed experiment by up to 15 J
      K(-1) mol(-1). Further insight into the quantum nature of water is provided by
      inspecting the temperature dependence of the frequencies. The harmonic
      approximation is further supported by the harmonic force and torque distributions
      and the very similar entropies obtained from the force and torque variances. All
      these results suggest that the single molecule harmonic oscillator approximation
      for water, although not exact, provides a rapid, insightful, and useful means to
      evaluate the thermodynamic properties of water from a computer simulation in a
      way that can account for the quantization of water's energy levels.

PMID- 18637684
TI  - Effect of pressure on the transport properties of ionic liquids: 1-alkyl-3
      methylimidazolium salts.
AB  - The self-diffusion coefficients (D) of the cation and anion in the ionic liquids
      1-hexyl-3-methylimidazolium and 1-octyl-3-methylimidazolium hexafluorophosphates
      ([HMIM]PF6 and [OMIM]PF6) and 1-butyl-3-methylimidazolium and 1-octyl-3
      methylimidazolium tetrafluoroborates ([BMIM]BF4) and ([OMIM]BF4) have been
      determined together with the electrical conductivities (kappa) of [HMIM]PF6 and
      [BMIM]BF4 under high pressure. The pressure effect on the transport coefficients
      is discussed in terms of velocity cross-correlation coefficients (VCCs or fij),
      the Nernst-Einstein equation (ionic diffusivity-conductivity), and the fractional
      form of the Stokes-Einstein relation (viscosity-conductivity and viscosity
      diffusivity). The (mass-fixed frame of reference) VCCs for the cation-cation,
      anion-anion, and cation-anion pairs are all negative and strongly pressure
      dependent, increasing (becoming less negative) with increasing pressure. VCCs are
      the more positive for the stronger ion-velocity correlations; therefore, f+ - is
      least negative in each case. In general, f- - is less negative than f+ +,
      indicating a smaller correlation of velocities of distinct cations than that for
      distinct anions. However, for [OMIM]PF6, the like-ion fii are very similar to one
      another. Plots of the VCCs for a given ion-ion correlation against fluidity
      (reciprocal viscosity) show the fij to be strongly correlated with the viscosity
      as either temperature or pressure are varied, that is, fij approximately
      fij(eta). The Nernst-Einstein deviation parameter, Delta, is nearly constant for
      each salt under the conditions examined. It is emphasized that nonzero values of
      Delta are not necessarily due to ion pairing but result from differences between
      the like-ion and unlike-ion VCCs, because Delta is proportional to (f+ + + f- - -
      2 f+ -). The diffusion and molar conductivity (Lambda) data are found to fit
      fractional forms of the Stokes-Einstein relationship, (LambdaT) proportional,
      variant (T/eta)(t) and Di proportional, variant (T/eta)(t), with t=(0.90+/-0.05)
      for all these ionic liquids, independent of both temperature and pressure within
      the ranges studied.

PMID- 18637685
TI  - Synthesis of a fluorescent xanthenic derivative useful for labeling amine
      residues.
AB  - The 2,5-dioxopyrrolidin-1-yl-4-(3-hydroxy-6-oxo-6H-xanthen-9-yl)-3-methylbenzoate
      has been synthesized as an amine-reactive derivative able to yield stable
      covalently labeled biopolymers. The new derivative has been used to label
      polyribocytidilic acid (5'), poly(C), amine residues. TG-II-poly(C) exhibits
      monoexponential decay at the physiological pH range. In addition, both steady
      state fluorescence intensity and fluorescence decay are also sensitive to
      solution pH. The large decrease in steady-state fluorescence upon hybridization
      allows it to be used as a nucleic acid probe in a homogeneous assay format. In
      summary, we report an efficient synthesis to obtain labeled RNA from commercially
      available materials in excellent yields.

PMID- 18637686
TI  - Homogeneous quaternization of cellulose in NaOH/urea aqueous solutions as gene
      carriers.
AB  - Quaternized celluloses (QCs) were homogeneously synthesized by reacting cellulose
      with 3-chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC) in NaOH/urea
      aqueous solutions. The structure and solution properties of the QCs were
      characterized by using elemental analysis, FTIR, (13)C NMR, SEC-LLS, viscometer,
      and zeta-potential measurement. The results revealed that water-soluble QCs, with
      a degree of substitution (DS) value of 0.20-0.63, could be obtained by adjusting
      the molar ratio of CHPTAC to anhydroglucose unit (AGU) of cellulose and the
      reaction time. The QC solutions in water displayed a typical polyelectrolyte
      behavior, and the intrinsic viscosity ([eta]) value determined from the Fuoss
      Strauss method increased with increasing DS value. Moreover, two QC samples (DS =
      0.46 and 0.63) were selected and studied as gene carriers. The results of gel
      retardation assay suggested that QCs could condense DNA efficiently. QCs
      displayed relatively lower cytotoxicity as compared with PEI, and QC/DNA
      complexes exhibited effective transfection compared to the naked DNA in 293T
      cells. The quaternized cellulose derivatives prepared in NaOH/urea aqueous
      solutions could be considered as promising nonviral gene carriers.

PMID- 18637687
TI  - Highly efficient system to deliver taxanes into tumor cells: docetaxel-loaded
      chitosan oligomer colloidal carriers.
AB  - Chitosan (CS) colloidal carriers, which consist of an oily core and a CS coating,
      were developed to facilitate a controlled intracellular delivery of docetaxel.
      The systems presented a particle size of <200 nm and a positive surface charge.
      As shown by the flow cytometry analysis, fluorescent CS carriers were rapidly
      internalized by human tumor cells. Fluorescence was observed in more than 80% of
      MCF7 (human breast adenocarcinoma) and almost 100% of A549 (human lung carcinoma)
      cells when a 2 h treatment with fluorescent CS carriers was given. A total of 24
      h after treatment, docetaxel-loaded CS carriers had an effect on cell
      proliferation that was significantly greater than that of free docetaxel. These
      results indicate that docetaxel remains fully active upon its encapsulation into
      the colloidal carriers and that these systems actively transport docetaxel into
      cancer cells and, thus, result in a significant increase in its antiproliferative
      effect.

PMID- 18637688
TI  - Cucurbitane-type triterpenoids from the stems of momordica charantia.
AB  - Four new cucurbitane-type triterpenes, cucurbita-5,23(E)-diene-3beta,7beta,25
      triol (1), 3beta-acetoxy-7beta-methoxycucurbita-5,23(E)-dien-25-ol (2), cucurbita
      5(10),6,23(E)-triene-3beta,25-diol (5), and cucurbita-5,24-diene-3,7,23-trione
      (6), together with four known triterpenes, 3beta,25-dihydroxy-7beta
      methoxycucurbita-5,23(E)-diene (3), 3beta-hydroxy-7beta,25-dimethoxycucurbita
      5,23(E)-diene (4), 3beta,7beta,25-trihydroxycucurbita-5,23(E)-dien-19-al (7), and
      25-methoxy-3beta,7beta-dihydroxycucurbita-5,23(E)-dien-19-al (8), were isolated
      from the methyl alcohol extract of the stems of Momordica charantia. The
      structures of the new compounds were elucidated by spectroscopic methods.

PMID- 18637689
TI  - Microwave-enhanced ionothermal CuAAC for the synthesis of glycoclusters on a
      calix[4]arene platform.
AB  - A tetra-azido calix[4]arene derivative was allowed to react with ethynyl tetra- O
      benzyl- C-galactoside in the presence of CuI and i-Pr 2EtN in three different
      ionic liquids, that is, [C 8dabco][N(CN) 2], [C 8dabco][Br], and Ammoeng 110.
      Reactions were performed at 80 degrees C by thermal and MW dielectric heating. In
      all cases, multiple cycloadditions took place to give a triazole-linked tetra- C
      galactosyl-calix[4]arene in up to 90% yield. The [C 8dabco][N(CN) 2] ionic liquid
      was also used to perform the multiclick reactions with propargyl O-lactoside and
      S-sialoside.

PMID- 18637690
TI  - On the two-ligand catalytic asymmetric deprotonation of N-boc pyrrolidine:
      probing the effect of the stoichiometric ligand.
AB  - To map out the stoichiometric ligand requirements in the two-ligand catalytic
      asymmetric deprotonation of N-Boc pyrrolidine, 24 different ligands have been
      evaluated; the highest enantioselectivity (90:10 er) was obtained by using s-BuLi
      in the presence of 0.3 equiv of (-)-sparteine and 1.3 equiv of a
      cyclohexanediamine-derived ligand.

PMID- 18637691
TI  - Probing the importance of the hemilabile site of bis(phosphine) monoxide ligands
      in the copper-catalyzed addition of diethylzinc to N-phosphinoylimines: discovery
      of new effective chiral ligands.
AB  - The hemilabile ligand Me-DuPHOS(O) 2 has proven to be a successful ligand for the
      copper-catalyzed addition of diethylzinc to N-phosphinoylimines. The
      corresponding alpha-chiral amines were obtained in high yields (80-98%) and
      enantiomeric ratios (19.0:1 to 99.0:1 er). Furthermore, this Cu* 2 catalytic
      system has been shown to be effective in the addition of diethylzinc to
      nitroalkenes and in the reduction of beta,beta-disubstituted vinyl phenyl
      sulfones. This paper describes a general structure/selectivity study in which the
      three ligand subunits (chiral phospholane-linker-labile coordinating group (Z))
      are systematically modified and tested in the copper-catalyzed addition of
      diethylzinc to the N-phosphinoylimine 1 derived from benzaldehyde. This study led
      to the discovery of a new class of effective chiral ligands that combine a chiral
      phospholane unit and an achiral phosphine oxide.

PMID- 18637692
TI  - Formal total synthesis of (+)-gephyrotoxin.
AB  - An efficient formal total synthesis of (+)-gephyrotoxin is described. The key
      step of our strategy relies on the diastereoselective reduction of a chiral
      pyrrolidine beta-enamino ester obtained by condensation of ( S)-phenylglycinol on
      a protected 8-hydroxy-3,6-dioxooctanoate.

PMID- 18637693
TI  - Rational or statistical routes from 1-acyldipyrromethanes to meso-substituted
      porphyrins. Distinct patterns, multiple pyridyl substituents, and amphipathic
      architectures.
AB  - New methodology is described for the synthesis of porphyrins bearing four (A 4,
      cis-A 2B 2, cis-ABC 2, trans-A 2B 2) or fewer (A, cis-AB, cis-A 2, trans-A 2)
      meso substituents. The method entails condensation of two 1-acyldipyrromethanes
      in the presence of a metal salt (MgBr 2, 3 mol equiv) and a noncoordinating base
      (DBU, 10 mol equiv) in a noncoordinating solvent (toluene) with heating
      (conventional or microwave irradiation) and exposure to air. The rational
      synthesis of trans-A 2B 2- or trans-A 2-porphyrins was achieved via condensation
      of two identical 1-acyldipyrromethanes. The statistical synthesis of various meso
      substituted porphyrins was achieved via condensation of two nonidentical 1
      acyldipyrromethanes. Both routes possess attractive features including (1) no
      scrambling, (2) good yield (up to 60%) at high concentration (100 mM) for the
      macrocycle-forming step, (3) reasonable scope (aryl, heteroaryl, alkyl, or no
      substituent), (4) short reaction time ( approximately 2 h) via microwave
      irradiation, (5) magnesium porphyrins as the products, which easily undergo
      demetalation, and (6) facile chromatographic purification. A key advantage of the
      statistical route is to obtain a cis-substituted porphyrin without the
      corresponding trans isomer. For example, reaction of an A/B-substituted 1
      acyldipyrromethane and the fully unsubstituted 1-formyldipyrromethane gave the
      magnesium chelates of three porphyrins: the trans-A 2B 2-porphyrin, the "hybrid"
      cis-AB-porphyrin, and porphine (no trans-AB-porphyrin can form), which were
      readily demetalated and separated as the free base species. Altogether 26 1
      acyldipyrromethanes and 26 target porphyrins have been prepared, including many
      with two different pyridyl substituents. One set of amphipathic porphyrins
      includes cis-A 2B 2- or cis-A 2BC-porphyrins wherein A = pentyl and B/C = pyridyl
      ( o-, m-, p-). Taken together, the rational and statistical routes enable facile
      conversion of readily available 1-acyldipyrromethanes to diverse porphyrins
      bearing 1-4 meso substituents for which access is limited via other methods.

PMID- 18637694
TI  - Co-complexes derived from alkene insertion to alkyne-dicobaltpentacarbonyl
      complexes: insight into the regioselectivity of pauson-khand reactions of
      cyclopropenes.
AB  - Described are the X-ray crystallographic and spectral properties of Co-complexes
      that were isolated from two Pauson-Khand reactions of chiral cyclopropenes. These
      are the first examples of isolated Co-complexes derived from the putative alkene
      insertion intermediates of Pauson-Khand reactions. The binuclear Co-complexes are
      coordinated to mu-bonded, five-carbon "flyover" carbene ligands. It is proposed
      that the complexes result from cyclopropane fragmentation subsequent to alkene
      insertion. The observation of these metal complexes provides a rationale for the
      origin of regioselectivity in Pauson-Khand reactions of cyclopropenes.

PMID- 18637695
TI  - Asymmetric silver-catalyzed reactions.

PMID- 18637696
TI  - Near-field Raman imaging and electromagnetic field confinement in the self
      assembled monolayer array of gold nanoparticles.
AB  - Spatial distribution of surface enhanced Raman activity is visualized for two
      dimensional (2D) nearly close-packed and well-ordered monolayer array of gold
      nanoparticles by using scanning near-field optical microscope. The 2D arrays
      exhibit highly nonuniform enhancement in Raman scattering, i.e., the regions
      along the edge of the 2D array are preferentially enhanced. We demonstrate that
      the spatial distribution of the localized electric field is also nonuniform and
      agrees well with that of the Raman enhancement.

PMID- 18637697
TI  - Effect of the guest size and shape on its binding dynamics with sodium cholate
      aggregates.
AB  - The binding dynamics of the guests acenaphthene, phenanthrene, fluorene, and
      acenaphthenol with sodium cholate aggregates were studied using laser flash
      photolysis and fluorescence. The location of the guests in the bile salt
      aggregate is determined by the guest's hydrophobicity, where acenaphthene,
      phenanthrene, and fluorene bind to the primary aggregates, while acenaphthenol
      binds to the secondary bile salt aggregates. The residence time of the guests in
      the primary aggregates and the access of ionic species from the aqueous phase to
      the guest in the aggregate depend on the size and the shape of the guest. These
      results show that bile salt aggregates are adaptable supramolecular host systems.

PMID- 18637699
TI  - Gram level synthesis of lead-free solder in the nanometer length scale obtained
      from tin and silver compounds using silicone oil.
AB  - A straightforward route to gram level synthesis of a pure phase of the Sn-Ag
      nanoalloy in an eutectic composition (Sn/Ag 96.5:3.5) in silicone oil is
      reported. The composition, morphology, and microstructure of the alloy were fully
      characterized. In a mixture of ethylene glycol and silicone oil, direct reduction
      of Sn(II) acetate and Ag(I) nitrate gave the Sn-Ag nanoalloy. The nanoalloy
      disintegrates by sonication and reforms by heating, leading to smaller particles
      with a melting point as low as 128 degrees C.

PMID- 18637698
TI  - Modulation of photo-oxidative DNA damage by cationic surfactant complexation.
AB  - The natural packaging of DNA in the cell by histones provides a particular
      environment affecting its sensitivity to oxidative damage. In this work, we used
      the complexation of DNA by cationic surfactants to modulate the conformation, the
      dynamics, and the environment of the double helix. Photo-oxidative damage
      initiated by benzophenone as the photosensitizer on a plasmid DNA complexed by
      dodecyltrimethylammonium chloride (DTAC), tetradecyltrimethylammonium chloride
      (TTAC), cetyltrimethyammonium chloride (CTAC) and bromide (CTAB) was detected by
      agarose gel electrophoresis. By fluorescent titration in the presence of ethidium
      bromide (EB) and agarose gel electrophoresis, we experimentally confirmed the
      complexation diagrams with a critical aggregation concentration on DNA matrix
      (CAC DNA) delimiting two regions of complexation, according to the DNA-phosphate
      concentration. The study of the photo-oxidative damage shows, for the first time,
      a direct correlation between the DNA complexation by these surfactants and the
      efficiency of DNA cleavage, with a maximum corresponding to the CAC DNA for DTAC
      and CTAC, and to DNA neutralization for CTAC and CTAB. The localization of a
      photosensitizer having low water solubility, such as benzophenone, inside the
      hydrophobic domains formed by the surfactant aggregated on DNA, locally increases
      the photoinduced cleavage by the free radical oxygen species generated. The
      inefficiency of a water-soluble quencher of hydroxyl radicals, such as mannitol,
      confirmed this phenomenon. The detection of photo-oxidative damage constitutes a
      new tool for investigating DNA complexation by cationic surfactants. Moreover,
      highlighting the drastically increased sensitivity of a complexed DNA to photo
      oxidative damage is of crucial importance for the biological use of surfactants
      as nonviral gene delivery systems.

PMID- 18637700
TI  - Chemical Research in Toxicology. In this issue.

PMID- 18637703
TI  - Analysis of diaphragm movement during tidal breathing and during its activation
      while breath holding using MRI synchronized with spirometry.
AB  - Using magnetic resonance imaging (MRI) in conjunction with synchronized
      spirometry we analyzed and compared diaphragm movement during tidal breathing and
      voluntary movement of the diaphragm while breath holding. Breathing cycles of 16
      healthy subjects were examined using a dynamic sequence (77 slices in sagittal
      plane during 20 s, 1NSA, 240x256, TR4.48, TE2.24, FA90, TSE1, FOV 328). The
      amplitude of movement of the apex and dorsal costophrenic angle of the diaphragm
      were measured for two test conditions: tidal breathing and voluntary breath
      holding. The maximal inferior and superior positions of the diaphragm were
      subtracted from the corresponding positions during voluntary movements while
      breath holding. The average amplitude of inferio-superior movement of the
      diaphragm apex during tidal breathing was 27.3+/-10.2 mm (mean +/- SD), and
      during voluntary movement while breath holding was 32.5+/-16.2 mm. Movement of
      the costophrenic angle was 39+/-17.6 mm during tidal breathing and 45.5+/-21.2 mm
      during voluntary movement while breath holding. The inferior position of the
      diaphragm was lower in 11 of 16 subjects (68.75 %) and identical in 2 of 16 (12.5
      %) subjects during voluntary movement compared to the breath holding. Pearson's
      correlation coefficient was used to demonstrate that movement of the costophrenic
      angle and apex of the diaphragm had a linear relationship in both examined
      situations (r=0.876). A correlation was found between the amplitude of diaphragm
      movement during tidal breathing and lung volume (r=0.876). The amplitude of
      movement of the diaphragm with or without breathing showed no correlation to each
      other (r=0.074). The movement during tidal breathing shows a correlation with the
      changes in lung volumes. Dynamic MRI demonstrated that individuals are capable of
      moving their diaphragm voluntarily, but the amplitude of movement differs from
      person to person. In this study, the movements of the diaphragm apex and the
      costophrenic angle were synchronous during voluntary movement of the diaphragm
      while breath holding. Although the sample is small, this study confirms that the
      function of the diaphragm is not only respiratory but also postural and can be
      voluntarily controlled.

PMID- 18637704
TI  - Plasma dependent and independent accumulation of betaine in male and female rat
      tissues.
AB  - Tissue betaine is an intracellular osmolyte that also provides a store of labile
      methyl groups. Despite these important biological roles, there are few data
      regarding tissue betaine content. We measured the betaine concentration of plasma
      and various tissues (brain, heart, lungs, liver, kidney, spleen, intestine,
      reproductive tissues, skeletal muscle and skin) in male and female rats and
      assessed whether there were any gender-specific differences in betaine content or
      distribution and whether there was any relationship between tissue accumulation
      and plasma levels. Betaine was highest in the liver and kidney with values
      ranging from 1.6 to 9.5 mmol/l and 2.0 to 5.4 mmol/l, respectively. Plasma
      betaine concentrations were significantly lower than tissue levels except in the
      brain (? 25 % of plasma) and skeletal muscle (similar to plasma). Regression
      analysis of the combined male and female data revealed a significant plasma
      related accumulation of betaine in the heart, skin and skeletal muscle, while the
      lung, liver, kidney, spleen, and intestine showed significant plasma-related and
      plasma-independent accumulations of betaine. The betaine content of the skin,
      liver and kidney was not significantly different between males and females, but
      in plasma and all tissues analyzed it was significantly higher in males (P<0.01).

PMID- 18637705
TI  - Effects of ectopic pacing on repolarization of the chicken left ventricle.
AB  - Effects of ectopic pacing on left ventricular repolarization were studied in six
      anesthetized open-chest chickens. In each animal, unipolar electrograms were
      acquired from as many as 98 sites with 14 plunge needles (seven transmural
      locations between epicardium and endocardium in each needle). Activation-recovery
      intervals (ARIs), corrected to the cycle length, were used for estimating
      repolarization. At baseline, the nonuniform ARI distribution in the left
      ventricle resulted in the apicobasal differences being greater than the
      transmural gradient. Nonuniform ARI prolongation caused by ectopic pacing
      resulted in decreasing the transmural repolarization gradient and increasing the
      differences in the apex-to-base direction. The basal, but not apical transmural
      differences contributed to the total left ventricular transmural gradient. The
      total left ventricular apicobasal gradient was contributed by the apicobasal
      differences in mid-myocardial and subendocardial layers more than in
      subepicardial ones. Thus, in in situ chicken hearts, the transmural and
      apicobasal ARI gradients exist within the left ventricle with the shortest ARIs
      in the basal subepicardium and the longest ARIs in the subendocardium of the
      apical and middle parts of the left ventricle. Apicobasal compared to transmural
      heterogeneity of local repolarization properties contributes more to the total
      left ventricular repolarization gradient.

PMID- 18637706
TI  - Prevalence of tidal expiratory flow limitation in preschool children with and
      without respiratory symptoms: application of the negative expiratory pressure
      (NEP) method.
AB  - Negative expiratory pressure (NEP) applied at the mouth during tidal expiration
      provides a non-invasive method for detecting expiratory flow limitation. Forty
      two children were studied, i.e. 25 children with different respiratory symptoms
      (R) and 17 without any respiratory symptoms (NR). Children were examined without
      any sedation. A preset NEP of -5 cm H(2)O was applied; its duration did not
      exceed duration of tidal expiration. A significance of FL was judged by
      determining of a flow-limited range (in % of tidal volume). FL was found in 48 %
      children of R group. No patient of the NR group elicited FL (P<0.001 R vs. NR).
      The frequency of upper airway collapses was higher in R group (12 children) than
      in NR group (5 children). In conclusion, a high frequency of tidal FL in the R
      group was found, while it was not present in NR group. A relatively high
      frequency of expiratory upper airway collapses was found in both groups, but it
      did not differ significantly. NEP method represents a reasonable approach for
      tidal flow limitation testing in non-sedated preschool children.

PMID- 18637707
TI  - Detection and possible role of proteasomes in the bronchoalveolar space of the
      injured lung.
AB  - Recent observations suggest the presence of 20S proteasomes (20S) in the lung
      epithelial lining fluid. However, the physiological relevance of 20S in the
      alveolar space and possible contribution to disease processes are unknown. Thus,
      we evaluated whether extracellular proteasomes could have a pathophysiological
      role in the injured lung using a rat model of lung contusion (LC).
      Bronchoalveolar lavage fluids (BALF) were obtained at various time points for up
      to 168 h after LC or sham procedure. Enzyme activities, ELISA and Western blots
      indicated enzymatically active 20S, the 19S subunit Rpt5 and ubiquitin in BALF.
      20S and ubiquitin increased significantly after LC, peaked at 24 h and normalized
      within 168 h. Mg(2+)/ATP-dependent peptidase activities were detectable 6-24 h
      after LC. BALF after LC also contained ubiquitin-protein-ligase activity.
      Addition of Mg(2+)/ATP to BALF after LC led to significant proteolysis and could
      be prevented with epoxomicin and EDTA. These data suggest for the first time that
      the Mg(2+)/ATP-dependent 26S proteasome complex exists outside the cell, is
      released into the lung epithelial lining fluid after LC and contributes to the
      proteolysis of the bulk of protein in the alveolar space of the injured lung. We
      infer that proteasome complexes may have a pathophysiological role during lung
      edema clearance.

PMID- 18637708
TI  - Alendronate lowers cholesterol synthesis in the central nervous system of rats -
      a preliminary study.
AB  - Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate
      synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their
      effect on cholesterol synthesis per se in the central nervous system (CNS)
      remains unknown. The aim of the present study was to examine possible influence
      of a representative agent alendronate on cholesterol synthesis rates in selected
      parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally
      administered either alendronate (3 mg/kg b.w.) or vehicle for 9 days. At the end
      of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal
      cord were isolated and cholesterol synthesis was determined using the technique
      of deuterium incorporation from deuterated water. In the alendronate group
      significant reductions of cholesterol synthesis rates were detected in frontal
      cortex, hippocampus and spinal cord (p<0.001). However, the experimental
      treatment did not produce a significant alteration in the levels of plasma
      cholesterol. In conclusion, this study brings the first experimental evidence of
      the inhibition of cholesterol biosynthesis with alendronate in central nervous
      system.

PMID- 18637710
TI  - Changes of parvalbumin expression in the spinal cord after peripheral
      inflammation.
AB  - Parvalbumin (PV) is a calcium-binding protein that is expressed by numerous
      neuronal subpopulations in the central nervous system. Staining for PV was often
      used in neuroanatomical studies in the past. Recently, several studies have
      suggested that PV acts in neurons as a mobile endogenous calcium buffer that
      affects temporo-spatial characteristics of calcium transients and is involved in
      modulation of synaptic transmission. In our experiments, expression of PV in the
      lumbar dorsal horn spinal cord was evaluated using densitometric analysis of
      immunohistological sections and Western-blot techniques in control and arthritic
      rats. There was a significant reduction of PV immunoreactivity in the superficial
      dorsal horn region ipsilateral to the arthritis after induction of the peripheral
      inflammation. The ipsilateral area and intensity of PV staining in this area were
      reduced to 38 % and 37 %, respectively, out of the total PV staining on both
      sides. It is suggested that this reduction may reflect decreased expression of PV
      in GABAergic inhibitory neurons. Reduction of PV concentration in the presynaptic
      GABAergic terminals could lead to potentiation of inhibitory transmission in the
      spinal cord. Our results suggest that changes in expression of calcium-binding
      proteins in spinal cord dorsal horn neurons may modulate nociceptive
      transmission.

PMID- 18637709
TI  - Red wine polyphenols affect the collagen composition in the aorta after oxidative
      damage induced by chronic administration of CCl(4).
AB  - Increased amount of collagen type I and decreased amount of type III is described
      in various pathological processes in the vascular wall. Polyphenols were shown to
      have protective effect on endothelium, decrease blood pressure and prevent
      oxidative damage induced by various stimuli. Tetrachlormethane (CCl(4)) is a
      toxic substance with known negative systemic effects induced by free radicals.
      Chronic administration of CCl(4) for 12 weeks led to an increase of collagen type
      I and a decrease of type III in the wall of aorta. Parallel administration of red
      wine polyphenols significantly reduced the increase of collagen type I, at the
      same time the content of type III rose to the level above controls. After 4 weeks
      of spontaneous recovery no changes were observed. If polyphenols were
      administered during the recovery period, there was a decrease of type I and an
      increase of type III collagen content in the aorta. It can be concluded that
      polyphenols have a tendency to lower the amount of type I and to increase the
      proportion of type III collagen in the wall of the aorta. These changes are
      significant in prevention or in regression of changes induced by chronic
      oxidative stress. This effect of polyphenols is most likely the result of their
      influence on MMP-1 and TIMP activities through which they positively influence
      the collagen types I and III content ratio in the vascular wall in favor of the
      type III collagen.

PMID- 18637711
TI  - Long-term effect of losartan administration on blood pressure, heart and
      structure of coronary artery of young spontaneously hypertensive rats.
AB  - Alterations in geometry and structure of coronary arteries have marked
      consequences on blood flow to the respective area. We evaluated long-term effect
      of losartan on blood pressure (BP), heart weight/body weight (HW/BW), geometry
      and structure of septal branch of coronary artery (RS) of young SHR and Wistar
      rats. Four-week-old Wistar rats and SHR were used. Losartan was administered (20
      mg/kg/day) in drinking water by gavage for 5 weeks. BP was measured by
      plethysmographic method. Cardiovascular system was perfused with a fixative (120
      mm Hg). RS was processed for electron microscopy. Wall thickness of intima +
      media (WT), inner diameter (ID), cross-sectional area of intima + media (CSA),
      volume densities (VD) of endothelial cells (EC), extracellular matrix (ECM) of
      intima, smooth muscle cells (SMC) and ECM of media were evaluated. BP of 4-week
      old SHR did not differ from that of Wistar rats. BP, HW/BW, WT, CSA, WT/ID, CSAs
      of SMC, ECM of media were increased in 9-week-old SHR, whereas their VD and CSA
      of EC were decreased. Losartan administration decreased BP and HW/BW in both
      groups. Geometry of RS was affected only in SHR (reduction of WT, CSA, WT/ID and
      increased of ID, circumferential tension, VD and CSA of EC). Losartan
      administration reduced BP and myocardial mass in both groups and beneficially
      affected geometry and structure of coronary artery in SHR.

PMID- 18637712
TI  - hsBAFF-upregulated intracellular free Ca(2+) homeostasis regulates ERK1/2
      activity and cell proliferation in B cells in vitro.
AB  - We studied hsBAFF activity in in vitro mouse splenic B cells. hsBAFF effects on
      intracellular free Ca(2+) concentration ([Ca(2+)](i)) were assayed, using a laser
      scanning confocal microscope with fluorescent probe, Fluo-3/AM. We showed that
      treatment of B cells with 0.5-5 microg/ml hsBAFF resulted in significantly higher
      [Ca(2+)](i) levels in a dose-dependent fashion at 12 and 24 h, respectively
      (p<0.05 or p<0.01 vs. control). Furthermore, we noticed that 2.5 microg/ml hsBAFF
      treated cells were significantly resistant to decrease of cellular viability
      induced by thapsigargin (Tg), an endoplasmic reticulum (ER) Ca(2+)-ATPase
      inhibitor (p<0.05 hsBAFF plus Tg group vs. Tg group). Thus hsBAFF may promote B
      cell survival by direct upregulation of [Ca(2+)](i) physiological homeostasis
      contributing to prevention of [Ca(2+)](i) dysfunction. Using immunocytochemistry
      and Western blot analysis, we found that the activation of ERK1/2 due to hsBAFF
      was triggered by a [Ca(2+)](i) -dependent pathway, leading to elevation of B cell
      proliferation. This is supported by the findings that intracellular Ca(2+)
      chelator BAPTA/AM attenuated phosphorylated ERK1/2 expression and cell
      proliferation in hsBAFF-stimulated B cells. hsBAFF-stimulated B cell
      proliferation was obviously reduced by mitogen extracellular kinase 1/2 (MEK1/2,
      upstream of ERK1/2) inhibitor U0126. Taken together, the main finding of this
      study is that hsBAFF elicits higher but homeostatic [Ca(2+)](i) levels, which
      regulates ERK1/2 activity and cell proliferation in in vitro B cells.

PMID- 18637713
TI  - Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox
      factor-1 (APE/ref-1) and DNA damage in the caudal region of acute and chronic
      spinal cord injured rats treated by embryonic neural stem cells.
AB  - The oxidative mechanisms of injury-induced damage of neurons within the spinal
      cord are not very well understood. We used a model of T8-T9 spinal cord injury
      (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury
      model, unilateral avulsion of the spinal cord causes oxidative stress of neurons.
      We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox
      effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the
      spinal cord region caudal to the lesion, and that DNA damage is an early upstream
      signal. The embryonic neural stem cell therapy significantly decreased DNA-damage
      levels in both study groups - acutely (followed up to 7 days after SCI), and
      chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA
      levels of APE/Ref-1 significantly increased after embryonic neural stem cell
      therapy in acutely and chronically injured animals when compared to acute and
      chronic sham groups. Our data has demonstrated that an increase of APE/Ref-1 mRNA
      levels in the caudal region of spinal cord strongly correlated with DNA damage
      after traumatic spinal cord injury. We suggest that DNA damage can be observed
      both in lesional and caudal regions of the acutely and chronically injured
      groups, but DNA damage is reduced with embryonic neural stem cell therapy.

PMID- 18637714
TI  - The effect of pheochromocytoma treatment on subclinical inflammation and
      endocrine function of adipose tissue.
AB  - The aim of our study was to evaluate the influence of surgical removal of
      pheochromocytoma on the endocrine function of adipose tissue and subclinical
      inflammation as measured by circulating C-reactive protein (CRP) levels. Eighteen
      patients with newly diagnosed pheochromocytoma were included into study.
      Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin
      and resistin levels were measured at the time of diagnosis and six months after
      surgical removal of pheochromocytoma. Surgical removal of pheochromocytoma
      significantly increased body weight, decreased both systolic and diastolic blood
      pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels
      were decreased by 50 % six months after surgical removal of pheochromocytoma
      (0.49+/-0.12 vs. 0.23+/-0.05 mg/l, p<0.05) despite a significant increase in body
      weight. Serum leptin, adiponectin and resistin levels were not affected by the
      surgery. We conclude that increased body weight in patients after surgical
      removal of pheochromocytoma is accompanied by an attenuation of subclinical
      inflammation probably due to catecholamine normalization. We failed to
      demonstrate an involvement of the changes in circulating leptin, adiponectin or
      resistin levels in this process.

PMID- 18637715
TI  - Increased gene expression and production of spinal cyclooxygenase 1 and 2 during
      experimental osteoarthritis pain.
AB  - Knowledge on the involvement of spinal COX-1 and COX-2 in pain due to
      osteoarthritis could be useful for better understanding of its pathogenesis and
      therapy. In this study we have investigated a long-term pattern of expression and
      production of spinal COX-1 and COX-2 in the model of osteoarthritis induced in
      rats by injection of monoiodoacetate (MIA) into the knee joint. MIA injection
      produced thermal hyperalgesia (assessed by the plantar test) and tactile
      allodynia (measured with von Frey hairs). The pain measures reached maximum on
      the fifht day, then remained relatively stable. The expression of spinal COX-2
      mRNA reached maximum on day 5 (5.2 times; P<0.001) and remained increased until
      day 31 (4.9 times; P<0.001). Expression of spinal COX-1 mRNA increased gradually
      reaching maximum on the day 31 (4.5 times; P<0.001) when the relative expression
      of both genes was almost equal. The production of both proteins was almost
      similar at the beginning of the experiment. The highest production of COX-2
      protein was observed on day 5 after the induction of osteoarthritis (increased
      3.9 times). The levels of COX-1 protein increased gradually with maximum on day
      31 (3.4 times). The present findings indicate that not only expression of COX-2
      mRNA but also that of COX-1 mRNA is significantly increased in the spine during
      osteoarthritis pain. Thus, in contrast to inflammatory pain, the upregulation of
      spinal COX-1 may be important in osteoarthritis pain.

PMID- 18637716
TI  - The cardiovascular response to lower body negative pressure in humans depends on
      seal location.
AB  - We tested whether seal location at iliac crest (IC) or upper abdomen (UA), before
      and during lower body negative pressure (LBNP), would affect thoracic electrical
      impedance, hepatic blood flow, and central cardiovascular responses to LBNP.
      After 30 min of supine rest, LBNP at -40 mm Hg was applied for 15 min, either at
      IC or UA, in 14 healthy males. Plasma density and indocyanine green
      concentrations assessed plasma volume changes and hepatic perfusion. With both
      sealing types, LBNP-induced effects remained unchanged for mean arterial pressure
      (-3.0+/-1.1 mm Hg), cardiac output (-1.0 l min(-1)), and plasma volume (-11 %).
      Heart rate was greater during UA (80.6+/-3.3 bpm) than IC (76.0+/-2.5 bpm)
      (p<0.01) and thoracic impedance increased more using UA (3.2+/-0.2 Omega) than IC
      (1.8+/-0.2 Omega) (p<0.0001). Furthermore, during supine rest, UA was accompanied
      by lower thoracic impedance (26.9+/-1.1 vs 29.0+/-0.8 Omega, p<0.001) and hepatic
      perfusion (1.6 vs 1.8 l.min(-1), p<0.05) compared to IC. The data suggest that
      the reduction in central blood volume in response to LBNP depends on location of
      the applied seal. The sealing in itself altered blood volume distribution and
      hepatic perfusion in supine resting humans. Finally, application of LBNP with the
      seal at the upper abdomen induced a markedly larger reduction in central blood
      volume and greater increases in heart rate than when the seal was located at the
      iliac crest.

PMID- 18637717
TI  - Investigation of mast cells in human gingiva following low-intensity laser
      irradiation.
AB  - OBJECTIVE: The aims of the present study were to investigate the effect of low
      intensity laser irradiation on the total number of mast cells as well as the
      percentage of degranulation in human gingiva. Blood vessel dilation was also
      evaluated. BACKGROUND DATA: It has been proposed that low-intensity laser
      irradiation can ameliorate pain, swelling, and inflammation. In periodontal
      tissue, mast cells may influence either the destructive events or the defense
      mechanism against periodontal disease via secretion of cytokines and through
      cellular migration to improve the healing process. Mast cells play an important
      role in the inflammatory process. METHODS: Twenty patients with gingival
      enlargement indicated for gingivectomy were selected. Gingival fragments were
      obtained from each patient and divided into three different groups before
      surgery. One fragment was removed without any irradiation. The two others were
      submitted to punctual irradiation with an energy density of 8 J/cm(2) at an
      output power of 50 mW at 36 Hz for 36 sec before gingivectomy. Nondegranulated
      and degranulated mast cells were counted in five areas of the gingival fragment
      connective tissue. Major and minor diameters of the blood vessels were also
      measured. RESULTS: Both red and infrared radiation promoted a significant
      increase in mast cell degranulation compared to controls; however, no
      statistically significant differences (p > 0.05) were observed between the
      irradiated groups. No significant differences among the groups were observed
      regarding blood vessel size. CONCLUSION: The results suggests that red and
      infrared wavelengths promote mast cell degranulation in human gingival tissue,
      although no dilation of blood vessels was observed. The effects of premature
      degranulation of mast cells in human tissue and the laser radiation protocol
      applied in this study encourage further investigations to extend these results
      into clinical practice.

PMID- 18637718
TI  - Decontamination of root canals with the gallium-aluminum-arsenide laser: an in
      vitro study.
AB  - OBJECTIVES: In this in vitro study, we investigated the bactericidal effects on
      root canals of 810-nm diode laser irradiation, alone or combined with sodium
      hypochlorite and citric acid irrigation. MATERIALS AND METHODS: One hundred
      sixteen single-rooted human teeth extracted for periodontal reasons were randomly
      divided into four experimental groups. The canal of each tooth was prepared with
      a conventional step-back technique and a pure culture of vancomycin-resistant
      Enterococcus faecalis grown in brain heart infusion broth was used to contaminate
      the root canal. The specimens were incubated at 37 degrees C for 15 d in a test
      tube filled with agar, adding fresh bacterial suspension every 48 h, and sent
      them for microbiological analysis and bacterial count. Subsequently they were
      divided into four groups: in group A, 29 teeth were irrigated with 2 mL of 10%
      citric acid solution; in group B, 29 teeth were irrigated with 2 mL 5.25% sodium
      hypochlorite (NaOCl) solution; in group C, 29 teeth were irradiated with 810-nm
      laser energy via a 200-microm optic fiber at 2.5 W power in pulsed mode (10 msec
      on and 10 msec off) for 5 sec; and in group D, 29 teeth were irrigated with
      NaOCl, irradiated with the laser, then irrigated with citric acid, and irradiated
      with the laser, followed again by NaOCl irrigation and laser irradiation. All the
      samples were again sent for microbiological analysis and bacterial count.
      RESULTS: Group A had a bactericidal effect of 0.041 log mean CFU, that of group B
      was 3.381 log mean CFU, and that of group C was 1.459 log mean CFU, whereas group
      D showed the best results, with a bactericidal effect of 7.178 log mean CFU.
      CONCLUSIONS: The use of NaOCl, citric acid, and diode laser energy together have
      a synergistic effect, increasing treatment efficacy and leading to significantly
      better decontamination of the root canal.

PMID- 18637719
TI  - Antimicrobial photodynamic action on dentin using a light-emitting diode light
      source.
AB  - OBJECTIVE: The aim of this study was the evaluation of two different
      photosensitizers activated by red light emitted by light-emitting diodes (LEDs)
      in the decontamination of carious bovine dentin. MATERIALS AND METHODS: Fifteen
      bovine incisors were used to obtain dentin samples which were immersed in brain
      heart infusion culture medium supplemented with 1% glucose, 2% sucrose, and 1%
      young primary culture of Lactobacillus acidophilus 10(8) CFU/mL and Streptococcus
      mutans 10(8) CFU/mL for caries induction. Three different concentrations of the
      Photogem solution, a hematoporphyrin derivative (1, 2, and 3 mg/mL) and two
      different concentrations of toluidine blue O (TBO), a basic dye (0.025 and 0.1
      mg/mL) were used. To activate the photosensitizers two different light exposure
      times were used: 60 sec and 120 sec, corresponding respectively to the doses of
      24 J/cm(2) and 48 J/cm(2). RESULTS: After counting the numbers of CFU per
      milligram of carious dentin, we observed that the use of LED energy in
      association with Photogem or TBO was effective for bacterial reduction in carious
      dentin, and that the greatest effect on S. mutans and L. acidophilus was obtained
      with TBO at 0.1 mg/mL and a dose of 48 J/cm(2). It was also observed that the
      overall toxicity of TBO was higher than that of Photogem, and that the
      phototoxicity of TBO was higher than that of Photogem. CONCLUSION: Based on our
      data we propose a mathematical model for the photodynamic effect when different
      photosensitizer concentrations and light doses are used.

PMID- 18637720
TI  - Detection and identification of Rickettsia species in the northeast of Italy.
AB  - This study was carried out using Ixodes ricinus ticks collected during 2005 and
      2006 from the Friuli Venezia Giulia (FVG) region in the northeastern part of
      Italy and an area along the Slovenian side of the western border of Italy. The
      results indicate that Rickettsia spp. is widely distributed throughout these
      areas, with the greatest prevalence in the central part of the FVG region. The
      prevalence of Rickettsia spp. was 4.5% during 2005 and 6.1% during 2006. By
      sequencing the 16S rRNA gene, we show for the first time the presence of
      Rickettsia helvetica in I. ricinus ticks in the FVG region and the presence of R.
      monacensis in ticks in both areas. Furthermore, we detected a sequence with a
      high homology with that of R. limoniae in a tick obtained from the alpine zone.

PMID- 18637721
TI  - Gene segment reassortment between American and Asian lineages of avian influenza
      virus from waterfowl in the Beringia area.
AB  - Since prehistoric times, the Bering Strait area (Beringia) has served as an
      avenue of dispersal between the Old and the New Worlds. On a field expedition to
      this area, we collected fecal samples from dabbling ducks, geese, shorebirds, and
      gulls on the Chukchi Peninsula, Siberia, and Pt. Barrow, Alaska, and
      characterized the subtypes of avian influenza virus present in them. Four of 202
      samples (2%) from Alaska were positive for influenza A virus RNA in two
      independent polymerase chain reaction (PCR)-based screening assays, while all
      shorebird samples from the Chukchi Peninsula were negative. Subtypes H3N8 and
      H6N1 were recorded once, while subtype H8N4 was found in two samples. Full-length
      sequences were obtained from the three unique isolates, and phylogenetic analysis
      with representative sequences for the Eurasian and North American lineages of
      influenza A virus showed that one HA gene clustered with the Eurasian rather than
      the North American lineage. However, the closest relative to this sequence was a
      North American isolate from Delaware described in 2002, indicating that a H6
      spillover from Asia has established itself in North America.

PMID- 18637722
TI  - Coinfection with four genera of bacteria (Borrelia, Bartonella, Anaplasma, and
      Ehrlichia) in Haemaphysalis longicornis and Ixodes sinensis ticks from China.
AB  - We studied coinfection with four genera of bacteria--Borrelia, Bartonella,
      Anaplasma, and Ehrlichia--in ticks collected between December 2005 and November
      2006 from Zhejiang Province and Liaoning Province. Four hundred fifty
      Haemaphysalis longicornis and 86 Ixodes sinensis ticks were collected and divided
      into 236 groups. Polymerase chain reaction (PCR) or nested PCR was used to detect
      the bacteria. The amplicons were sequenced and compared to published sequences.
      Phylogenic analysis was performed with MEGA3.1 and the data were analyzed using
      SPSS 11.0. Borrelia, Bartonella, Anaplasma, and Ehrlichia positive rates were
      30.1% (71/236), 28.8% (68/236), 1.3% (3/236), and 0.8% (2/236), respectively. One
      tick was coinfected with all four bacteria (Borrelia, Bartonella, Anaplasma, and
      Ehrlichia) and another group was coinfected with three bacteria, Borrelia,
      Bartonella, and Ehrlichia. Statistical analysis showed most coinfections were
      significant, indicating that once a tick was infected with one bacteria, there
      was a greater chance to be infected with another bacteria.

PMID- 18637723
TI  - Relapsing fever spirochetes retain infectivity after prolonged in vitro
      cultivation.
AB  - Borrelia hermsii and Borrelia burgdorferi, two closely related spirochetes, are
      the etiological agents of tick-borne relapsing fever and Lyme disease,
      respectively. Previous studies have shown the loss of infectivity of B.
      burgdorferi is associated with in vitro cultivation. This diminished infectivity
      of B. burgdorferi has occurred as early as three in vitro passages, and the loss
      of plasmids have been observed with these less virulent to noninfective cultures.
      The effects of long-term in vitro cultivation on B. hermsii have not been
      investigated. However, understanding the degree of genomic degradation during in
      vitro cultivation is important for investigating pathogenic mechanisms of
      spirochetes. In this study, we analyzed the effects of continuous in vitro
      cultivation on the genomic composition and infectivity of B. hermsii and B.
      turicatae.We report that all seven isolates of B. hermsii and the one isolate of
      B. turicatae examined retained infectivity in mice after 1 year of continuous in
      vitro cultivation. Furthermore, there were few apparent differences in the
      plasmid profiles after long-term cultivation. Two isolates of B. hermsii remained
      infective after high passage despite losing a portion of the 200-kb linear
      plasmid containing the fhbA gene encoding the factor H binding protein. Also,
      sequence analysis of multiple B. hermsii isolates demonstrated two types of fhbA
      with complete congruence with the two genomic groups of B. hermsii spirochetes.
      Therefore, these results suggest that relapsing fever spirochetes are genetically
      stable during in vitro cultivation, and the fhbA-containing segment of DNA that
      is lost during cultivation is not required for infection.

PMID- 18637724
TI  - Knowledge, attitudes, and behaviors regarding Lyme disease prevention among
      Connecticut residents, 1999-2004.
AB  - Lyme disease, caused by the tick-transmitted bacterium Borrelia burgdorferi, is
      the most common vector-borne disease in the United States. We surveyed residents
      of three Connecticut health districts to evaluate the impact of intensive
      community-wide education programs on knowledge, attitudes, and behaviors to
      prevent Lyme disease. Overall, 84% of respondents reported that they knew a lot
      or some about Lyme disease, and 56% felt that they were very or somewhat likely
      to get Lyme disease in the coming year. During 2002-2004, the percentage of
      respondents who reported always performing tick checks increased by 7% and the
      percentage of respondents who reported always using repellents increased by 5%,
      whereas the percentage of respondents who reported avoiding wooded areas and
      tucking pants into socks decreased. Overall, 99% of respondents used personal
      protective behaviors to prevent Lyme disease. In comparison, 65% of respondents
      reported using environmental tick controls, and increased use of environmental
      tick controls was observed in only one health district. The majority of
      respondents were unwilling to spend more than $100 on tick control. These results
      provide guidance for the development of effective Lyme disease prevention
      programs by identifying measures most likely to be adopted by residents of Lyme
      disease endemic communities.

PMID- 18637726
TI  - The effect of timing of mechanical stimulation on proliferation and
      differentiation of goat bone marrow stem cells cultured on braided PLGA
      scaffolds.
AB  - Bone marrow stromal cells (BMSCs) have been shown to proliferate and produce
      matrix when seeded onto braided poly(L-lactide/glycolide) acid (PLGA) scaffolds.
      Mechanical stimulation may be applied to stimulate tissue formation during
      ligament tissue engineering. This study describes for the first time the effect
      of constant load on BMSCs seeded onto a braided PLGA scaffold. The seeded
      scaffolds were subjected to four different loading regimes: Scaffolds were
      unloaded, loaded during seeding, immediately after seeding, or 2 days after
      seeding. During the first 5 days, changing the mechanical environment seemed to
      inhibit proliferation, because cells on scaffolds loaded immediately after
      seeding or after a 2-day delay, contained fewer cells than on unloaded scaffolds
      or scaffolds loaded during seeding (p<0.01 for scaffolds loaded after 2 days).
      During this period, differentiation increased with the period of load applied.
      After day 5, differences in cell content and collagen production leveled off.
      After day 11, cell number decreased, whereas collagen production continued to
      increase. Cell number and differentiation at day 23 were independent of the
      timing of the mechanical stimulation applied. In conclusion, static load applied
      to BMSCs cultured on PLGA scaffolds allows for proliferation and differentiation,
      with loading during seeding yielding the most rapid response. Future research
      should be aimed at elucidating the biomechanical and biochemical characteristics
      of tissue formed by BMSCs on PLGA under mechanical stimulation.

PMID- 18637727
TI  - Synthetic octacalcium phosphate augments bone regeneration correlated with its
      content in collagen scaffold.
AB  - Previous studies have shown that synthetic octacalcium phosphate (OCP)
      facilitates in vitro osteoblastic cell differentiation in an OCP dose-dependent
      manner and that a complex of OCP and collagen (OCP/collagen) enhances critical
      sized rat calvaria defects more than OCP alone. The present study was designed to
      investigate whether the bone regenerative properties of OCP/collagen are
      augmented in an OCP dose-dependent manner, thereby establishing a suitable
      composition of this composite as a bone substitute material. OCP/collagens with a
      wide range of mixing ratios from 23:77 to 83:17, including the previously
      examined composition (77:23), were prepared by blending granules of OCP with
      atelocollagen and molded into a disk as an implant. A critical-sized defect was
      made in rat calvaria, and each disk was implanted into the defect for 4 or 12
      weeks and then examined radiographically, histologically, and
      histomorphometrically. Mouse bone marrow-derived stromal ST-2 cells were cultured
      in dishes pre-coated with OCP/collagen or OCP alone with different OCP contents
      to determine the capacity of cell attachment and proliferation up to 14 days.
      Histological and radiographic examinations showed that newly formed bone was
      observed in relation to OCP granules within the collagen matrix.
      Histomorphometric analysis confirmed that increasing the amount of OCP in
      collagen matrices resulted in progressive enhancement of bone regeneration and
      that the ratio 83:17 generated the maximum repair level of approximately 64% of
      the defect at 12 weeks. OCP/collagen promoted the proliferation and attachment of
      ST-2 cells more than OCP alone regardless of OCP content. Fourier transform
      infrared spectroscopy analysis of the coatings after the incubation indicated
      that OCP tended to convert to apatite regardless of the presence of collagen. The
      present study demonstrated that the osteoconductive characteristics of
      OCP/collagen can be displayed in an OCP dose-dependent manner. The results
      suggest that collagen promotes the proliferation and attachment of host
      osteoblastic cells on OCP/collagen composite implants.

PMID- 18637729
TI  - Oligonucleotide-mediated gene targeting in human hepatocytes: implications of
      mismatch repair.
AB  - Gene therapy using viral vectors for liver diseases, particularly congenital
      disorders, is besought with difficulties, particularly immunologic reactions to
      viral antigens. As a result, nonviral methods for gene transfer in hepatocytes
      have also been explored. Gene repair by small synthetic single-stranded
      oligodeoxynucleotides (ODNs) produces targeted alterations in the genome of
      mammalian cells and represents a great potential for nonviral gene therapy. To
      test the feasibility of ODN-mediated gene repair within chromosomal DNA in human
      hepatocytes, two new cell lines with stably integrated mutant reporter genes,
      namely neomycin and enhanced green fluorescent protein were established.
      Targeting theses cells with ODNs specifically designed for repair resulted in
      site-directed and permanent gene conversion of the single-point mutation of the
      reporter genes. Moreover, the frequency of gene alteration was highly dependent
      on the mitotic activity of the cells, indicating that the proliferative status is
      an important factor for successful targeting in human hepatocytes. cDNA array
      expression profiling of DNA repair genes under different cell culture conditions
      combined with RNA interference assay showed that mismatch repair (MMR) in
      actively growing hepatocytes imposes a strong barrier to efficient gene repair
      mediated by ODNs. Suppression of MSH2 activity in hepatocytes transduced with
      short hairpin RNAs (shRNAs) targeted to MSH2 mRNA resulted in 25- to 30-fold
      increase in gene repair rate, suggesting a negative effect of MMR on ODN-mediated
      gene repair. Taken together, these data suggest that under appropriate conditions
      nonviral chromosomal targeting may represent a feasible approach to gene therapy
      in liver disease.

PMID- 18637730
TI  - Evaluation of various polyethylenimine formulations for light-controlled gene
      silencing using small interfering RNA molecules.
AB  - Photochemical internalization (PCI) is a technology based on a photosensitizer
      that photochemically destabilizes endosomal membranes after illumination,
      resulting in the release of endocytosed material into the cytosol. In this study,
      we investigated the potential of using polyethylenimine (PEI) for light
      controlled delivery of small interfering RNA (siRNA) molecules via the endocytic
      pathway. PEI formulations with different molecular weights (MW) and chemical
      forms (linear [L]/branched [B]) were investigated for their capacity to deliver
      siRNA molecules with or without PCI at variable nitrogen/phosphorus (N/P) ratios
      and illumination doses. By targeting the S100A4 gene in an osteosarcoma cell
      model system, potent gene silencing was observed in samples treated with PCI
      compared with samples not treated with PCI. The effect of light-controlled gene
      silencing was dependent on several factors, including light-doses and MW,
      chemical form, as well as on the N/P ratio of the PEI formulations. This study
      demonstrates the first success in using PEI formulations as siRNA carriers for
      light-controlled gene silencing with the objective of future use in in vivo
      applications.

PMID- 18637732
TI  - siRNA-mediated silencing of c-kit in mouse primary spermatogonial cells induces
      cell cycle arrest.
AB  - Several genes/gene products are known to act in a concert to regulate the process
      of spermatogenesis. One such gene is c-kit, a transmembrane tyrosine kinase
      receptor which plays an indispensable role in the maturation and differentiation
      of spermatogonial germ cells (SGCs). In the present study, siRNA approach was
      used to assess the role of c-kit in survival and proliferation of murine primary
      SGCs. The effect of different concentrations of anti-c-kit siRNA-1 and siRNA-2
      (0.15, 0.315, 0.625, 1.25, 2.50, 5, and 10 nM) on c-kit protein and mRNA
      expression at post-transfection time (0, 6, 12, 24, 48, and 72 hours) was
      assessed using an array of techniques such as flow cytometry, ELISA, Western
      blot, and RT-PCR. Transfection of cells with anti-c-kit siRNAs (0.15-10 nM) at
      various time points after (0-72 hours) showed significant knockdown c-kit mRNA
      and protein expression. MTT, Alamar blue assays, and RT-PCR were used to
      investigate the effects of c-kit silencing on survival, proliferation,
      distribution, and apoptosis of cells. Experiments were also conducted to
      determine the effects of c-kit knockdown on cell cycle distribution, DNA
      laddering, and apoptosis. The results indicated that the transfection with anti-c
      kit siRNA induces DNA fragmentation and cell cycle arrest at G(2)/M phase leading
      to significant reduction in cell viability and proliferation. In addition,
      enhanced suppression of c-kit protein in P815 cells was observed after
      transfection as compared to ES-E14TG2alpha cells, suggesting early onset of c-kit
      protein repression in P815 cells leading to prolongation in cell doubling time.
      In conclusion, our data provide the first evidence of specific knockdown of c-kit
      expression in mouse primary SGCs, which emphasizes the critical role played by c
      kit in germ cell survival, proliferation, and apoptosis.

PMID- 18637731
TI  - Novel aptamer inhibitors of human immunodeficiency virus reverse transcriptase.
AB  - Primer-template-based double-stranded nucleic acids capable of binding human
      immunodeficiency virus reverse transcriptase (HIV-RT) with high affinity were
      used as starting material to develop small single-stranded loop-back DNA
      aptamers. The original primer-templates were selected using a SELEX (Systematic
      Evolution of Ligands by EXponential enrichment) approach and consisted of 46- and
      50-nt primer and template strands, respectively. The major determinant of the
      approximately 10-fold tighter binding in selected sequences relative to control
      primer-templates was a run of 6.8 G residues at the 3' primer end. Sixty, thirty
      seven, twenty-seven, and twenty-two nucleotide loop-back single-stranded versions
      that retained the base pairs near the 3' primer terminus were constructed. Both
      the 60- and 37-nt versions retained high affinity for RT with K(d) values of
      approximately 0.44 nM and 0.66 nM, respectively. Random sequence primer-templates
      of the same length had K(d)s of approximately 20 nM and approximately 161 nM. The
      shorter 27- and 22-nt aptamers bound with reduced affinity. Several modifications
      of the 37-nt aptamer were also tested including changes to the terminal 3' G
      nucleotide and internal bases in the G run, replacement of specific nucleotides
      with phosphothioates, and alterations to the 5' overhang. Optimal binding
      required a 4- to 5-nt overhang, and internal changes within the G run had a
      pronounced negative effect on binding. Phosphothioate nucleotides or the presence
      of a 3' dideoxy G residue did not alter affinity. The 37-nt aptamer was a potent
      inhibitor of HIV-RT in vitro and functioned by blocking binding of other primer
      templates.

PMID- 18637733
TI  - Induction of apoptosis in murine neuroblastoma by systemic delivery of
      transferrin-shielded siRNA polyplexes for downregulation of Ran.
AB  - The polymer, OEI-HD, based on beta-propionamide-cross-linked oligoethylenimine
      and its chemical transferrin conjugate were evaluated for siRNA delivery into
      murine Neuro2A neuroblastoma cells in vitro and in vivo. An 80% silencing of
      luciferase expression in neuroblastoma cells, stably transfected with a
      luciferase gene, was obtained using standard OEI-HD polyplexes or transferrin
      conjugated shielded OEI-HD polyplexes. The Ras-related nuclear protein Ran was
      selected as a therapeutically relevant target protein. Systemic delivery of
      transferrin-conjugated OEI-HD/RAN siRNA formulations (three intravenous
      applications at 3 days interval) resulted in >80% reduced Ran protein expression,
      apoptosis, and a reduced tumor growth in Neuro2A tumors of treated mice. The
      treatment was not associated with signs of acute toxicity or significant changes
      in weight, hematology parameters, or liver enzymes (AST, ALT, or AP) of mice. All
      our results demonstrate that OEI-HD/siRNA formulations can knockdown genes in
      tumor cells in vitro and in vivo in mice in the absence of unspecific toxicity.

PMID- 18637734
TI  - Antisense oligonucleotides targeting universally conserved 26S rRNA domains of
      plant ribosomes at different steps of polypeptide elongation.
AB  - A ribosome undergoes significant conformational changes during elongation of
      polypeptide chain that are correlated with structural changes of rRNAs. We tested
      nine different antisense oligodeoxynucleotides complementary to the selected,
      highly conserved sequences of Lupinus luteus 26S rRNA that are engaged in the
      interactions with tRNA molecules. The ribosomes were converted either to pre- or
      to posttranslocational states, with or without prehybridized oligonucleotides,
      using tRNA or mini-tRNA molecules. The activity of those ribosomes was tested via
      the so-called binding assay. We observed well-defined structural changes of
      ribosome's conformation during different steps of the elongation cycle of protein
      biosynthesis. In this article, we present that (i) before and after
      translocation, fragments of domain V between helices H70/H71 and H74/H89 do not
      have to interact with nucleotides 72-76 of the acceptor arm of A-site tRNA; (ii)
      helix H69 does not have to interact with DHU arm of tRNA in positions 25 and 26
      after forming the peptide bond, but before translocation; (iii) helices H69 and
      H70 interact weakly with nucleotides 11, 12, 25, and 26 of A-site tRNA before
      forming a peptide bond in the ribosome; (iv) interactions between helices H80,
      H93 and single-stranded region between helices H92 and H93 and CCAend of P-site
      tRNA are necessary at all steps of elongation cycle; and (v) before and after
      translocation, helix H89 does not have to interact with nucleotides in positions
      64-65 and 50-53 of A-site tRNA TPsiC arm.

PMID- 18637737
TI  - The history and development of the Human Genetics Society of Australasia.
AB  - The Human Genetics Society of Australasia is a vibrant professional society with
      more than 900 members that promotes and regulates the practice of human and
      medical genetics in Australia and New Zealand. The growth of human genetics was
      stimulated by the development of diagnostic clinical cytogenetics laboratories in
      the early to mid 1960s. This coincided with the recognition by medical
      specialists, mainly pediatricians, that genetic disorders, especially inborn
      errors of metabolism and birth defects, were of clinical interest and potentially
      challenging areas for their skills. The organization of professionals in human
      genetics was slow to evolve. There was an early Western Australian Human Genetics
      Society, and the cytogenetics community had begun to meet annually from about
      1966 but was coordinated by a mailing list rather than as a formal organization.
      In 1976, as part of the celebrations of the Centenary Year of the Adelaide
      Children's Hospital, a clinical genetics meeting involving several high profile
      international speakers and most of the senior medical geneticists in Australia
      and New Zealand along with the annual meeting of the loose-knit cytogeneticists
      group agreed that a small working group be charged with setting up a Human
      Genetics Society. The society was formally incorporated in South Australia in
      1977.

PMID- 18637735
TI  - Chemical modification patterns compatible with high potency dicer-substrate small
      interfering RNAs.
AB  - Dicer-substrate small interfering RNAs (DsiRNAs) are synthetic RNA duplexes that
      are processed by Dicer into 21-mer species and show improved potency as triggers
      of RNA interference, particularly when used at low dose. Chemical modification
      patterns that are compatible with high potency 21-mer small interfering RNAs have
      been reported by several groups. However, modification patterns have not been
      studied for Dicer-substrate duplexes. We therefore synthesized a series of
      chemically modified 27-mer DsiRNAs and correlated modification patterns with
      functional potency. Some modification patterns profoundly reduced function
      although other patterns maintained high potency. Effects of sequence context were
      observed, where the relative potency of modification patterns varied between
      sites. A modification pattern involving alternating 2'-O-methyl RNA bases was
      developed that generally retains high potency when tested in different sites in
      different genes, evades activation of the innate immune system, and improves
      stability in serum.

PMID- 18637738
TI  - Forty years from markers to genes.
AB  - There have been incredible advances made in human genetics over the past 40
      years. I have set out in the next few pages to describe just some of these
      changes and to illustrate how they unfolded through my own experiences.

PMID- 18637739
TI  - Why is alpha-actinin-3 deficiency so common in the general population? The
      evolution of athletic performance.
AB  - 'We can now explain how this common genetic variation influences athletic
      performance as well as why it has become so common in the general population.
      There is a fascinating link between factors that influence survival in ancient
      humans and the factors that contribute to athletic abilities in modern man.' The
      human ACTN3 gene encodes the protein alpha-actinin-3, a component of the
      contractile apparatus in fast skeletal muscle fibers. In 1999, we identified a
      common polymorphism in ACTN3 (R577X) that results in absence of alpha-actinin-3
      in more than one billion people worldwide, despite the ACTN3 gene being highly
      conserved during human evolution. In 2003, we demonstrated that ACTN3 genotype
      influences elite athletic performance, and the association between ACTN3 genotype
      and skeletal muscle performance has since been replicated in athletes and non
      athlete cohorts. We have also studied the evolution of the R577X allele during
      human evolution and demonstrated that the null (X) allele has undergone strong,
      recent positive selection in Europeans and Asian populations. We have developed
      an Actn3 knockout mouse model that replicates alpha-actinin-3 deficiency in
      humans and has already provided insight into the role of alpha-actinin-3 in the
      regulation of skeletal muscle metabolism, fibre size, muscle mass and contractile
      properties. In particular, mouse muscle lacking alpha-actinin-3 uses energy more
      efficiently, with the fast fibers displaying metabolic and contractile properties
      of slow oxidative fibers. While this favors endurance activities, the trade off
      is that the muscle cannot generate the rapid contractions needed to excel in
      sprinting. We propose that the shift towards more efficient aerobic muscle
      metabolism associated with alpha-actinin-3 deficiency also underlies the adaptive
      benefit of the 577X allele. Our future studies will focus on the effect of ACTN3
      genotype on response to exercise and ageing, and the onset and severity of muscle
      disease phenotype.

PMID- 18637740
TI  - Approaches to finding the molecular basis of mitochondrial oxidative
      phosphorylation disorders.
AB  - Inherited disorders of mitochondrial oxidative phosphorylation are the most
      common group of inborn errors of metabolism and cause a wide range of clinical
      presentations. Mitochondrial DNA encodes 13 protein subunits required for
      oxidative phosphorylation plus 22 transfer RNAs and two ribosomal RNAs, and
      mutations in most of these genes cause human disease. Nuclear genes encode most
      of the protein subunits and all other proteins required for mitochondrial
      biogenesis and mitochondrial DNA replication and expression. Mutations in 64
      nuclear genes and 34 mitochondrial genes are now known to cause mitochondrial
      disease and many novel mitochondrial disease genes await discovery. The genetic
      complexity of oxidative phosphorylation means that maternal, autosomal recessive,
      autosomal dominant and X-linked modes of inheritance can occur, along with de
      novo mutations. This complexity presents a challenge in planning efficient
      molecular genetic diagnosis of patients with suspected mitochondrial disease. In
      some situations, clinical phenotype can be strongly predictive of the underlying
      genotype. However, more often this is not the case and it is usually helpful,
      particularly with pediatric patients, to determine whether the activity of one or
      more of the individual oxidative phosphorylation enzymes is deficient before
      proceeding with mutation analysis. In this review we will summarize the genetic
      bases of mitochondrial disease and discuss some approaches to integrate
      information from clinical presentation, laboratory findings, family history, and
      imaging to guide molecular investigation.

PMID- 18637741
TI  - Chromosomal rearrangements and novel genes in disorders of eye development,
      cataract and glaucoma.
AB  - Disorders of eye development such as microphthalmia and anophthalmia (small and
      absent eyes respectively), anterior segment dysgenesis where there may be
      pupillary and iris anomalies, and associated cataract and glaucoma, often lead to
      visual impairment or blindness. Currently treatment options are limited, as much
      is unknown about the molecular pathways that control normal eye development and
      induce the aberrant processes that lead to ocular defects. Mutation detection
      rates in most of the known genes are generally low, emphasizing the genetic
      heterogeneity of developmental ocular defects. Identification of the disease
      genes in these conditions improves the clinical information available for
      affected individuals and families, and provides new insights into the underlying
      biological processes for facilitation of better treatment options. Investigation
      of chromosomal rearrangements associated with an ocular phenotype has been
      especially powerful for disease gene identification. Molecular characterization
      of such rearrangements, which pinpoints the region by physically disrupting the
      causative gene or its regulatory sequences, allows for rapid elucidation of
      underlying genetic factors that contribute to the phenotype. Genes including
      PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4 have been identified in
      this way to be associated with developmental eye disorders. More recently, new
      methods in chromosomal analysis such as comparative genomic hybridization (CGH)
      microarray, have also enhanced our ability in disease gene identification.

PMID- 18637742
TI  - Population screening for reproductive risk for single gene disorders in
      Australia: now and the future.
AB  - Abstract As the results of the Human Genome Project are realized, it has become
      technically possible to identify carriers of numerous autosomal and X-linked
      recessive disorders. Couples at risk of having a child with one of these
      conditions have a number of reproductive options to avoid having a child with the
      condition should they wish. In Australia the haemoglobinopathies are the only
      group of conditions for which population screening is widely offered and which is
      government funded. In some Australian states there are also population screening
      programs for cystic fibrosis and autosomal recessive conditions more common in
      Ashkenazi Jewish individuals which are generally offered on a user pays basis. It
      is predicted that as consumer demand increases and testing becomes cheaper, that
      many people planning or in the early stages of pregnancy will have carrier
      screening for multiple genetic conditions. This will have significant
      implications for genetic counseling, laboratory and prenatal testing resources.
      In addition such screening raises a number of ethical issues including the value
      of lives of those born with genetic conditions for which screening is available.

PMID- 18637744
TI  - Co-twin controls: facioplasty / twin research reviews: congenital anomalies;
      personality and coital orgasmic infrequency; physical activity participation /
      newsworthy: twins, triplets and quads; school legislation update; premature twins
      in court.
AB  - Abstract The usefulness of monozygotic (MZ) twins for studying the efficacy of
      different face lift techniques is described. The data suggest that no particular
      procedure out of four under consideration is superior to any other. Next, reviews
      of recent twin studies of congenital anomalies, personality traits and coital
      orgasmic infrequency, and physical activity participation are presented. Finally,
      timely topics of public interest are also described. They include a rare birth
      consequence of artificial reproductive technology, an update on state legislation
      regarding parents' rights to decide the classroom placement of their young twins,
      and medical malpractice lawsuits involving premature twins.

PMID- 18637747
TI  - Session-by-session report of low frequency Kleinian psychoanalysis: establishing
      analytic contact with a borderline patient.
AB  - There is virtually no literature regarding the psychoanalytic treatment of
      patients with less than three times a week frequency other than those articles
      that include the word psychotherapy in the title. Even though more lenient
      positions are taken in public forums and between colleagues, there is still a
      vast political distance between what is considered kosher psychoanalysis and
      "that other procedure." The leading publication for psychoanalysis worldwide, the
      International Journal of Psychoanalysis, now includes articles on psychoanalytic
      psychotherapy. It is remarkable, but never mentioned, to notice how the cases and
      clinical process written about are usually indistinguishable from the cases and
      clinical process in all the other articles concerning psychoanalysis. This author
      presents material based in the belief that if a consistent pattern of
      transference analysis has taken place along with regular exploration of phantasy
      and defense, then, regardless of frequency, analytic contact can take place. This
      treatment is then regarded as psychoanalysis. In other words, psychoanalysis
      becomes defined by clinical process rather than external criteria. This article
      examines the establishment of analytic contact with a borderline patient within a
      twice-a-week, on-the-couch, Kleinian framework.

PMID- 18637748
TI  - A family experiential model of recovery after brain injury.
AB  - The Family Experiential Model (FEM) described in this article is a therapeutic
      "navigation tool" for families traversing the recovery process with their loved
      one after brain injury. Its conception furnishes a personal voice and the
      pragmatic "stoplight model" depicts how the family's myriad of powerful emotions
      affects the chosen path in the rehabilitation and recovery process. As an example
      of mentalizing, the FEM is a healing tool that instills mutual insight and
      empathy among the family, psychotherapist, and patient. The application of the
      FEM to individual and group treatment in a holistic treatment milieu is also
      described.

PMID- 18637749
TI  - Differential patterns of lifetime multiple anxiety disorder comorbidity between
      Latino adults with bipolar I and major depressive disorders.
AB  - BACKGROUND: To determine the lifetime rates of panic disorder, obsessive
      compulsive disorder (OCD), social phobia, and posttraumatic stress disorder
      (PTSD) among adult Latino patients with major depressive disorder (MDD) and
      bipolar disorder (BPD), and whether there are dose-response relationships between
      loading for comorbid anxiety disorders, the probability of having BPD, and
      attributes of severity of illness. METHODS: In a public sector clinic for the
      indigent located in a semiclosed rural community, 187 consecutively presenting
      affectively ill Latino patients were evaluated by use of the Structured Clinical
      Interview for DSM-IV. Polarity and the lifetime prevalence of panic disorder,
      OCD, social phobia, and PTSD were determined. Logistic regression was used to
      test associations. Trends in positive predictive values (PPVs) and likelihood
      ratios were assessed to determine whether dose-response relationships existed
      between loading for comorbid anxiety disorders and the likelihood of having BPD
      as opposed to MDD, psychosis, suicidal ideation, and suicide attempts. RESULTS:
      Of 187 subjects, 118 (63.1%) had MDD and 69 (36.9%) had BPD. The odds ratio of a
      patient with BPD, relative to MDD, of having panic disorder was 4.6 (p< .0001),
      OCD 7.6 (p< .0001), social phobia 6.0 (p< .0001) and PTSD 5.3 (p< .0001). The PPV
      of having BPD was 91.3% and of having psychotic features 83.0% if one had all
      four anxiety disorders. There was a dose-response relationship between loading
      for comorbid anxiety disorders and the likelihood of having had a suicide attempt
      (but not suicidal ideation). CONCLUSIONS: As previously reported by us for
      juvenile patients, Latino adults with BPD had a remarkably high risk of having
      each anxiety disorder relative to patients with MDD. The results indicate that
      the risk of having BPD, having a psychosis, and making a suicide attempt becomes
      increasingly great as the number of comorbid anxiety disorders increases. These
      data, which are consistent with the notion of anxious bipolarity, provide further
      support for a possible anxious diathesis in bipolar disorder.

PMID- 18637751
TI  - Practical consequences of hepatitis C virus quasispecies for target-specific
      antivirals.

PMID- 18637752
TI  - Natural prevalence of hepatitis C virus variants with decreased sensitivity to
      NS3.4A protease inhibitors in treatment-naive subjects.
AB  - BACKGROUND: The prevalence and clinical implications of naturally occurring
      variants that are resistant to hepatitis C virus (HCV) protease inhibitors in
      treatment-naive patients has not been reported. We report here the prevalence of
      such variants and their effect on clinical response. METHODS: Population sequence
      analysis of the NS3.4A protease was conducted in 570 treatment-naive subjects.
      RESULTS: Most subjects (98%) had wild-type virus. The remaining subjects had the
      following variants present in significant proportions (100%): V36M, 0.9%; R155K,
      0.7%; V170A, 0.2%; and R109K, 0.2%. The V36M, R109K, and V170A substitutions
      confer low-level resistance (<7-fold) to protease inhibitors in replicon cells.
      The R155K substitution confers low-level resistance to telaprevir (TVR) and
      boceprevir and confers high-level resistance (>70-fold) to BILN 2061 and ITMN
      191. Five subjects with the V36M or R109K variant were treated with 8-24 weeks of
      TVR and peginterferon-alpha2a (P) with or without ribavirin (R). Four achieved a
      sustained viral response, and 1 was lost to follow-up. In subjects with the R155K
      variant, TVR/PR provided greater antiviral activity than PR alone; however, the
      antiviral response was lower than that observed in subjects with wild-type virus.
      CONCLUSION: High levels of naturally occurring protease inhibitor-resistant
      variants were uncommon (<1% each) in HCV treatment-naive patients. TVR/PR
      efficiently inhibited V36M and R109K variants and contributed partial antiviral
      activity against the R155K variant. As new HCV agents are evaluated in clinical
      trials, it will be important to monitor the effect of baseline variants on
      sensitivity.

PMID- 18637753
TI  - Detrimental effects of mannose-binding lectin (MBL2) promoter genotype XA/XA on
      HIV-1 vertical transmission and AIDS progression.
AB  - BACKGROUND: The literature on the involvement of mannose-binding lectin (MBL) in
      human immunodeficiency virus (HIV) transmission and acquired immunodeficiency
      syndrome (AIDS) is conflicting. Polymorphisms in the MBL2 gene reduce the level
      of protein and alter its structure. Thus, we investigated whether MBL2 alleles
      and plasma concentrations of MBL are associated with perinatal HIV transmission
      and disease progression. METHODS: Frequencies of MBL2 allelic variants (B, C, D,
      and X) were estimated among 345 HIV-exposed children and 147 blood donors. AIDS
      free time was evaluated for different MBL2 genotypes and MBL plasma levels. The
      median duration of follow-up was 96.5 months. RESULTS: In the Argentinean
      population, gene frequencies of MBL2 variants were 18%, 15%, and 3% for the X, B,
      and D alleles, respectively, with no identified C allele. The haplotype XA/XA was
      associated with an 8-fold risk of acquiring HIV-1 (P= .054; odds ratio [OR], 8.11
      [95% confidence interval {CI}, 0.96-67.86]) and almost a 3-fold risk of
      progression to pediatric AIDS (P= .026; OR, 2.81 [95% CI, 1.14-7.47]). We also
      found an independent positive correlation between the rate of AIDS progression
      and MBL plasma concentration (P= .008; OR, 1.28 [95% CI, 1.07-1.55]).
      CONCLUSIONS: Our results demonstrate that homozygosity for the MBL2 promoter
      genotype XA/XA is an important genetic determinant of HIV-1 acquisition through
      vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism
      that remains to be established.

PMID- 18637754
TI  - A novel mode of transmission for human enterovirus infection is swimming in
      contaminated seawater: implications in public health and in epidemiological
      surveillance.

PMID- 18637755
TI  - Single-day, patient-initiated famciclovir therapy versus 3-day valacyclovir
      regimen for recurrent genital herpes: a randomized, double-blind, comparative
      trial.
AB  - BACKGROUND: Recurrent genital herpes is a major problem for patients worldwide.
      Early episodic treatment with short-course therapy is effective, often stopping
      progression of outbreaks. This study is the first head-to-head comparison of
      single-day famciclovir (1000 mg administered twice daily) versus 3-day
      valacyclovir (500 mg administered twice daily) for episodic therapy in
      immunocompetent patients. METHODS: In this multicenter, multinational, double
      blind, parallel-group study, 1179 adults with a history of recurrent genital
      herpes were randomized 1:1 to receive either famciclovir or valacyclovir.
      Patients initiated treatment within 6 h after a recurrence. The primary objective
      was to establish noninferiority of single-day famciclovir, compared with a 3-day
      course of valacyclovir, in time to healing of all nonaborted lesions in a
      modified intent-to-treat population. RESULTS: This study established that single
      day famciclovir therapy was noninferior to 3-day valacyclovir therapy in reducing
      time to healing of all nonaborted genital herpes lesions (median time to healing,
      4.25 days vs. 4.08 days). Approximately one-third of patients in each treatment
      group had aborted genital herpes episodes, suggesting that both treatments have
      similar efficacy in preventing outbreaks or progression of lesions beyond the
      papule stage. There was no significant difference in time to resolution of
      symptoms associated with recurrence. The overall incidence of adverse events was
      similar (23.2% for the famciclovir group vs. 22.3% for the valacyclovir group),
      with headache, nausea, diarrhea, vomiting, and abdominal pain reported most
      often. CONCLUSIONS: Single-day famciclovir (1000 mg administered twice daily) was
      similar to 3-day valacyclovir (500 mg administered twice daily) in both efficacy
      and safety, representing a more convenient treatment for immunocompetent adults
      with recurrent genital herpes.

PMID- 18637756
TI  - An outbreak of concurrent echovirus 30 and coxsackievirus A1 infections
      associated with sea swimming among a group of travelers to Mexico.
AB  - BACKGROUND: Enteroviruses are shed in human stool and can cause a wide spectrum
      of illness. They are the leading cause of aseptic meningitis. METHODS: In 2004,
      the Connecticut Department of Public Health investigated a meningitis cluster
      among persons returning from a school-organized trip to Mexico. RESULTS: Among 29
      travelers (25 teenagers and 4 adult chaperones), 21 became acutely ill. Viral
      culture and nucleic acid amplification testing of stool (n=27) and cerebrospinal
      fluid (n=4) specimens identified enteroviral infection in 20 of 28 travelers from
      whom any specimen was obtained; 4 had echovirus 30 only, 11 had coxsackievirus
      (CV) A1 only, 4 had both echovirus 30 and CVA1, and 1 had CVA5 only. Illness
      onset dates were tightly clustered 4 days after a prolonged swim in the Gulf of
      Mexico. Time spent swimming was significantly associated with the odds of
      enteroviral infection (univariate odds ratio for each additional hour swimming,
      14.3; 95% confidence interval, 1.3-154.3). Headache, fever, vomiting, and nausea
      occurred more frequently among the echovirus 30-infected travelers than among the
      uninfected control subjects (P< .05). The most frequent symptoms among travelers
      infected with only CVA1 identified were nausea and diarrhea (36% each), but
      neither was significantly associated with CVA1 infection; 5 patients with CVA1
      infection were asymptomatic. CONCLUSIONS: We identified multiple enteroviruses
      among the travelers. Clustered illness onsets suggest point-source exposure,
      which likely was a sea swim in sewage-contaminated seawater. Novel molecular
      amplification and sequencing methodologies were required to recognize the rarely
      identified CVA1, but it is ambiguous whether CVA1 infection caused illness.
      Travelers should be aware of risks associated with swimming in natural waters
      when visiting areas where there is limited sewage treatment.

PMID- 18637758
TI  - Human papillomavirus genotype distribution in external acuminata condylomata: a
      Large French National Study (EDiTH IV).
AB  - BACKGROUND: External acuminata condylomata (EAC) are among the most common
      sexually transmitted diseases. Although it is understood that low-risk human
      papillomavirus (HPV) genotypes 6 and 11 are associated with EAC, there have only
      been a few, small, published studies reporting the genotype-specific prevalence
      of HPV. The objective of our study was to assess the prevalence of HPV genotypes
      for a large number of cases involving both men and women and to evaluate the
      potential benefit of a quadrivalent (genotypes 6, 11, 16, and 18) HPV vaccine in
      France. METHODS: A total of 256 women and 260 men who presented with EAC to
      French gynecologists, dermatologists, and proctologists were prospectively
      recruited during the period January through April 2007. Specimens were collected
      with a cytobrush, and the HPV genotype was determined using the INNO-LiPA assay
      (Innogenetics), which detects 24 HPV genotypes. RESULTS: Four hundred twenty
      three beta-globin-positive samples could be analyzed. The median age of patients
      was 30 years (range, 18-72 years). The overall prevalence of HPV DNA in patients
      with EAC was 99% (33% of patients were coinfected with another pathogen). Low
      risk genotypes predominated, with a prevalence of 89%. The most prevalent
      genotypes were 6 (69%) and 11 (16%), followed by 16 (9%), 51 (8%), 52 (7%), 66
      (6%) 53 (5%), 31 (3%), and 18 (3%). The cumulative prevalence of genotypes 6 and
      11 was 83%, and the cumulative prevalence of genotypes 6, 11, 16, and 18 was 88%.
      CONCLUSIONS: This study is, to our knowledge, the first large, multicenter survey
      to provide solid data on HPV genotype distribution among patients with EAC. Our
      results provide strong evidence that, in France, the most prevalent HPV genotypes
      in persons with EAC are 6 and 11. Because of its 99% efficacy for the prevention
      of EAC and a vaccine coverage of 100%, the quadrivalent HPV vaccine could prevent
      62%-87% of EAC cases in France.

PMID- 18637757
TI  - Defining responses to therapy and study outcomes in clinical trials of invasive
      fungal diseases: Mycoses Study Group and European Organization for Research and
      Treatment of Cancer consensus criteria.
AB  - Invasive fungal diseases (IFDs) have become major causes of morbidity and
      mortality among highly immunocompromised patients. Authoritative consensus
      criteria to diagnose IFD have been useful in establishing eligibility criteria
      for antifungal trials. There is an important need for generation of consensus
      definitions of outcomes of IFD that will form a standard for evaluating treatment
      success and failure in clinical trials. Therefore, an expert international panel
      consisting of the Mycoses Study Group and the European Organization for Research
      and Treatment of Cancer was convened to propose guidelines for assessing
      treatment responses in clinical trials of IFDs and for defining study outcomes.
      Major fungal diseases that are discussed include invasive disease due to Candida
      species, Aspergillus species and other molds, Cryptococcus neoformans,
      Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential
      pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or
      mycological data and gaps in knowledge.

PMID- 18637759
TI  - Habitat dependence and correlations between elasticities of long-term growth
      rates.
AB  - In population biology, elasticity is a measure of the importance of a demographic
      rate on population growth. A relatively small amount of stochasticity can
      substantially impact the dynamics of a population whose growth is a function of
      deterministic and stochastic processes. Analyses of natural populations
      frequently neglect the latter. Even in a population that fluctuates substantially
      with time, the results of a deterministic perturbation analysis correlated
      strongly with results of a perturbation analysis of the long-run stochastic
      growth rate. Population growth was, however, not uniformly sensitive to
      demographic rates across different environmental conditions. The overall
      correlation between deterministic and stochastic perturbation analysis may be
      high, but environmental variability can dramatically alter the contributions of
      demographic rates in different environmental conditions. This potentially
      informative detail is neglected by deterministic analysis, yet it highlights one
      difficulty when extrapolating results from long-term analysis to shorter-term
      environmental change.

PMID- 18637761
TI  - Differences between the physiologic and psychologic effects of aromatherapy body
      treatment.
AB  - BACKGROUND: The wide use of herbal plants and essential oils for the prevention
      and treatment of diseases dates back to ancient times. However, the scientific
      basis for the beneficial effects of such plants and oils has not been precisely
      clarified. OBJECTIVE: The purpose of this study was to evaluate the effects of
      aromatherapy body treatment on healthy subjects. DESIGN: We compared the
      physiologic and psychologic effects of aromatherapy body treatment (E), massage
      treatment with carrier oil alone (C), and rest in healthy adults. SUBJECTS: Seven
      (7) female and 6 male volunteers participated as subjects. INTERVENTIONS: Each
      subject underwent 3 trials, in which the Advanced Trail Making Test (ATMT) was
      given as a stress-inducing task before and after 1 of 3 treatments. OUTCOME
      MEASURES: The State Anxiety Inventory (SAI), the Visual Analog Scale, and the
      Face Scale were used to assess anxiety, feelings, and mood, respectively.
      RESULTS: After the treatments, the SAI score and the feelings of fatigue were
      decreased, the positive and comfortable feelings were increased, and mood
      improved significantly in C and E. Furthermore, significant declines in the
      feelings of mental and total fatigue were maintained even after the second ATMT
      in E. On the other hand, the cortisol concentration in the saliva did not show
      significant changes in any of the trials. Secretory immunoglobulin A levels in
      the saliva increased significantly after all treatments. CONCLUSIONS: We conclude
      that massage treatments, irrespective of the presence of essential oils, are more
      advantageous than rest in terms of psychologic or subjective evaluations but not
      in terms of physiologic or objective evaluations. Furthermore, as compared to
      massage alone, the aromatherapy body treatment provides a stronger and continuous
      relief from fatigue, especially fatigue of mental origin.

PMID- 18637760
TI  - Leukemia inhibitory factor secretion is a predictor and indicator of early
      progenitor status in adult bone marrow stromal cells.
AB  - Bone marrow-derived stromal cells (BMSCs) are defined by their ability to self
      renew and differentiate into at least three mesenchymal cell types (bone,
      adipose, and cartilage). The inability to isolate a reliably efficacious and
      homogeneous population of early progenitor cells has limited efforts to increase
      their therapeutic potential. In this study, we focused on identifying protein
      markers that may be employed to predict the efficacy of a cultured BMSC
      population. Markers of progenitor status were identified by comparing BMSCs at
      early and late passage, donor-matched skin fibroblasts, and commercially
      available dermal fibroblast cell lines. Differentiation potential was determined
      according to in vitro assays of osteogenesis, adipogenesis, and chondrogenesis.
      Early-passage BMSCs differentiated into all three lineages, whereas late-passage
      BMSCs and both fibroblast preparations did not. To identify novel markers of
      early progenitors, microarray transcript analysis between early-passage BMSCs and
      fibroblasts was performed. Messenger RNA encoding the cytokine leukemia
      inhibitory factor (LIF) was identified as differentially expressed. Enzyme-linked
      immunosorbent assay on conditioned media confirmed that LIF secretion was much
      higher from early progenitor BMSCs than donor-matched or commercial lines of
      fibroblasts and dropped with extensive expansion or induction of differentiation.
      In clonally expanded BMSCs, colonies that retained progenitor status expressed
      significantly higher levels of LIF than those that failed to differentiate. Our
      results indicate that LIF expression may represent a marker to quantify the
      differentiation potential of BMSCs and may be especially suited for the rapid,
      noninvasive quality control of clinical preparations.

PMID- 18637762
TI  - Effectiveness of the herbal medicine daikenchuto for radiation-induced enteritis.
AB  - BACKGROUND: Radiation-induced enteritis is a serious clinical problem for which
      there is currently no recommended standard management. Daikenchuto (DKT) is a
      Japanese herbal medicine that has been used to treat adhesive bowel obstruction
      in Japan. This report describes a patient with radiation-induced enteritis whose
      clinical symptoms were much improved by treatment with DKT. METHOD: The patient
      was administered DKT, a traditional Japanese herbal formula, orally (2.5 g 3
      times daily). Abdominal distention was evaluated objectively with computed
      tomography. RESULTS: Gastrointestinal symptoms associated with radiation-induced
      enteritis were controlled successfully with DKT treatment. CONCLUSIONS: DKT
      treatment may be useful for the management of radiation-induced enteritis.

PMID- 18637763
TI  - DNA microarray analysis of the effect on inflammation in patients treated with
      acupuncture for allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis affects approximately 30% of adults and up to 40%
      of children in industrialized societies. Medicines available for relief of
      allergic rhinitis symptoms include antihistamines, decongestants, leukotriene
      inhibitors, topical hormones, and corticosteroids. However, the negative side
      effects of antiallergic medicines cause many patients with allergic rhinitis to
      choose traditional Chinese medical treatments, such as taking Chinese herbs or
      treatment with acupuncture. OBJECTIVES: This study assessed the effect of
      acupuncture for treatment of allergic rhinitis. METHODS: Eighteen (18) patients
      with allergic rhinitis were treated with acupuncture 8 times over a 4-week
      period, and peripheral blood of these patients was collected at each visit for
      analysis of gene expression via cDNA microarray. To estimate the therapeutic
      effect of acupuncture objectively, patients completed the rhinoconjunctivitis
      quality of life questionnaire (RQLQ) before and after acupuncture therapy.
      RESULTS: Based upon patients' response to the RQLQ, acupuncture therapy
      significantly reduced allergic rhinitis symptoms, including nasal symptoms, non
      hay fever symptoms, and sleep and practical problems (associated with daily
      activities). In addition, expression of interleukin-1 receptor-alpha (IL1R1) in
      peripheral blood was significantly decreased at 2 hours, 24 hours, and 4 weeks
      after acupuncture treatment in these patients. CONCLUSIONS: To our knowledge,
      this is the first report of cDNA microarray analysis of differential gene
      expression in the peripheral blood of patients with allergic rhinitis before and
      after acupuncture treatment. Our data suggest that the balance between T-helper 1
      and T-helper 2 cell-derived proinflammatory versus anti-inflammatory cytokines
      might be improved by acupuncture treatment.

PMID- 18637764
TI  - Interaction between warfarin and Panax ginseng in ischemic stroke patients.
AB  - BACKGROUND: Today, the combined use of Oriental herbal medicines and Western
      biomedical medicines has been a prevalent yet controversial practice. Case
      reports and healthy volunteer trials have had conflicting results on the effect
      Panax ginseng has on warfarin's pharmacologic action, some reporting a reductive
      and others a potentiating influence. OBJECTIVE: This study investigated the
      interaction between warfarin and P. ginseng by observing the prothrombin time
      (PT) and the international normalized ratio (INR) in ischemic stroke patients who
      did not have a history of taking warfarin. DESIGN: Randomized, open-label,
      controlled study. SUBJECTS: Twenty-five (25) patients newly diagnosed with
      ischemic stroke by brain computed tomography or magnetic resonance imaging in the
      Korean Medical Hospital, Kyung Hee University (Seoul, Republic of Korea).
      INTERVENTION: Ischemic stroke patients were randomized into 2 groups: the ginseng
      group (n = 12), given both P. ginseng and warfarin, and the control group (n =
      13), given only warfarin, both for 2 weeks. The warfarin dose was restricted to 2
      mg in the first week and 5 mg in the second week. RESULTS: The peak values and
      the international normalized ratio (INR) and prothrombin time (PT) areas under
      the curve (AUC) in both groups significantly increased compared to those at
      baseline. However, there was no statistically significant difference in peak
      values and INR and PT AUC between groups in both the first and second weeks.
      CONCLUSIONS: This study suggests that coadministration of P. ginseng and warfarin
      in ischemic stroke patients does not influence the pharmacologic action of
      warfarin.

PMID- 18637765
TI  - General practice in 2008: a time of metamorphosis.

PMID- 18637766
TI  - Cancer care: what role for the general practitioner?

PMID- 18637767
TI  - Pay for performance systems in general practice: experience in the United
      Kingdom.

PMID- 18637768
TI  - What impact will the change of federal government have on Australian general
      practice?

PMID- 18637769
TI  - Estimating prevalence of common chronic morbidities in Australia.
AB  - OBJECTIVES: To estimate prevalence of selected diagnosed chronic diseases among
      patients attending general practice, in the general practice patient population,
      and in the Australian population, and to compare population estimates with those
      of the National Health Survey (NHS). DESIGN, SETTING AND PARTICIPANTS: In late
      2005, 305 general practitioners each provided data for about 30 consecutive
      patients (total, 9156) as part of the BEACH (Bettering the Evaluation And Care of
      Health) program, a continuous national study of general practice activity. GPs
      used their knowledge of the patient, patient self-report, and medical records as
      sources. MAIN OUTCOME MEASURES: Crude prevalence of each listed condition
      currently under management among surveyed patients, and adjusted prevalence for
      the general practice patient population, and the national population. RESULTS:
      39.6% of respondents had none of the listed conditions diagnosed; 30.0% had a
      cardiovascular problem (uncomplicated hypertension, 17.6%; ischaemic heart
      disease, 9.5%); 24.8% had a psychological problem (depression, 14.2%; anxiety,
      10.7%); 22.8% had arthritis, mostly osteoarthritis (20.0%); 10.7% had asthma; and
      8.3% had diabetes, mostly type 2 (7.2%). Adjustment to the population attending
      general practice resulted in lower estimates for cardiovascular disease,
      arthritis and diabetes but had little effect on prevalence of asthma and
      psychological problems. After adjusting for non-attenders, about one in five
      people in the population had a cardiovascular problem, a similar proportion had a
      psychological problem, 14.8% had arthritis, and about 10% had asthma,
      hyperlipidaemia and gastro-oesophageal reflux disease. Estimates were similar to
      NHS results for any arthritis, asthma, and malignant neoplasms; higher for any
      cardiovascular problem; far higher for specific cardiovascular diseases,
      cerebrovascular disease and hyperlipidaemia; and almost twice the NHS estimate
      for psychological problems (particularly depression and anxiety). Estimates for
      type 1 diabetes aligned with NHS results, but were far higher for "all diabetes"
      and type 2 diabetes. CONCLUSIONS: This study offers an alternative, perhaps more
      accurate, approach to measurement of disease prevalence than the NHS approach,
      which relies on respondent self-report alone. It provides valid prevalence
      estimates with the help of GPs at a fraction of the cost of the NHS. This study
      could be repeated annually to augment other data sources and better define
      existing health needs in the population.

PMID- 18637770
TI  - Prevalence and patterns of multimorbidity in Australia.
AB  - OBJECTIVES: To estimate the prevalence and patterns of multimorbidity in a sample
      of patients attending general practice, in the population who attended general
      practice in 2005, and in the Australian population. DESIGN, SETTING AND
      PARTICIPANTS: Secondary analyses of data from a study of prevalence of selected
      conditions (a substudy of the BEACH [Bettering the Evaluation And Care of Health]
      program); data were provided by 305 general practitioners for 9156 patients seen
      in July-November 2005, based on knowledge of the patient, patient self-report,
      and medical records. Listed conditions were classified according to the
      Cumulative Illness Rating Scale morbidity domains. MAIN OUTCOME MEASURES:
      Prevalence of morbidity in each domain; prevalence of specific patterns of
      multimorbidity (defined as presence of morbidity in two or more domains).
      RESULTS: Prevalence of multimorbidity was estimated as 37.1% of surveyed
      patients, 29.0% of people who attended a GP in 2005, and 25.5% of the Australian
      population. Prevalence and complexity (number of domains present) increased with
      age: 83.2% of surveyed patients aged 75 years or older had multimorbidity, 58.2%
      had morbidity in three or more domains, and 33.4% in four or more. Prevalence of
      multimorbidity did not differ between the sexes. The most common morbidity
      combinations were arthritis/chronic back pain + vascular disease (15.0% of
      sample), a psychological problem + vascular disease (10.6%) and arthritis/chronic
      back pain + a psychological problem (10.6%). We estimate that 10.6% of people
      attending a GP in 2005 and 9.3% of the population have arthritis/chronic back
      pain + vascular disease (+/- other morbidity types studied), and this group
      accounted for about 15.2 million Medicare-claimed general practice encounters in
      2005. CONCLUSIONS: This study provides the first insight into prevalence and
      patterns of multimorbidity in Australia. Knowledge of the common combinations of
      multimorbidity may help in planning the health services needed in the future by
      an ageing population with an increasing burden of multimorbidity.

PMID- 18637771
TI  - Sharing or shuffling--realities of chronic disease care in general practice.

PMID- 18637772
TI  - Timely cancer diagnosis and management as a chronic condition: opportunities for
      primary care.
AB  - One in three men and one in four women in Australia will be diagnosed with cancer
      in the first 75 years of life. The majority will survive the cancer and
      ultimately die from unrelated causes. Many cancer patients and their families
      will experience some physical, social, economic and psychological sequelae,
      regardless of the prognosis. A recurring theme is that patients are disadvantaged
      by the lack of coordination of care and their needs are not being adequately met.
      We argue that greater integration of care through a multidisciplinary team of
      professionals, peer support groups and primary health practitioners functioning
      within a care hub could offer better practical and psychosocial supportive care
      for patients and their families.

PMID- 18637773
TI  - Information overload: what's behind it, what's beyond it?

PMID- 18637774
TI  - The effect of advertising in clinical software on general practitioners'
      prescribing behaviour.

PMID- 18637775
TI  - Investigation of cardiovascular risk factors in type 2 diabetes in a rural
      Australian Division of General Practice.
AB  - OBJECTIVE: To examine the changes in cardiovascular disease (CVD) risk factors
      for a cohort of patients with type 2 diabetes in general practice. DESIGN AND
      SETTING: A 4-year retrospective cohort study using extracted data from an active
      Division of General Practice diabetes register in Australia. PARTICIPANTS: 628
      patients (297 female; 331 male) with type 2 diabetes who participated in the
      diabetes program of the Southern Highlands Division of General Practice and for
      whom evaluation data were recorded each year from 2002 to 2005. MAIN OUTCOME
      MEASURES: Changes in the following CVD risk factors over time: body mass index
      (BMI), serum lipid levels (total cholesterol [TC], low-density lipoprotein
      cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total
      triglycerides [TG]), systolic and diastolic blood pressure (BP), and glycated
      haemoglobin (HbA(1c)) level. RESULTS: After adjusting for age, sex, duration and
      clustering, there was significant improvement in serum lipid levels (TC and LDL
      C; P < 0.05) over time; and there was no significant change in BP, HbA(1c) level
      or BMI. Older patients had significantly worse systolic BP, but significantly
      better BMI and lipid levels than younger patients. Longer duration of diabetes
      was associated with worse systolic BP and HbA(1c) level, but better HDL-C level.
      People with higher BMI were likely to have worse systolic BP, and HDL-C and
      HbA(1c) levels, but better TC level than those with lower BMI. CONCLUSIONS:
      Improving BP, HbA(1c) level and BMI may be more difficult than improving lipid
      levels. There is a need for more intensive and comprehensive interventions to
      reduce the total risk of CVD.

PMID- 18637776
TI  - Health care for people with intellectual disability.

PMID- 18637777
TI  - I went to work with a "cold" ...

PMID- 18637778
TI  - Measuring patient-reported outcomes: moving from clinical trials into clinical
      practice.

PMID- 18637779
TI  - Access to general practitioners in South Australia: a population survey.
AB  - OBJECTIVE: To determine the timeliness of access to general practitioner
      appointments in South Australia. DESIGN AND SETTING: Face-to-face interviews with
      a random and representative sample of South Australians living in metropolitan
      Adelaide and country towns with a population of 1000 or more in 2007.
      PARTICIPANTS: 2507 people aged 15 years and over who had seen a GP in the
      previous 12 months. MAIN OUTCOME MEASURES: Waiting times for obtaining an
      appointment with a GP, patients' perceptions about appointment waiting times, and
      waiting times at the GP's surgery. RESULTS: Most respondents reported that for
      their last visit with a GP, they were able to be seen on the same day (39%) or
      within 1 or 2 working days (33%); 20% waited more than 2 working days for their
      appointment. Nine per cent of respondents (159/1764) reported waiting more than 2
      working days because an earlier appointment was not available. Respondents
      reporting lower levels of household income were more likely to report longer
      waits for GP appointments. Most respondents (78%) felt that they were able to
      make a GP appointment as soon as they thought necessary. At the surgery, 46% of
      respondents were seen within 15 minutes, but 13% waited 45 minutes or longer.
      CONCLUSIONS: In general, access to GPs is timely, and most South Australians
      reported that for their last GP visit they were able to make an appointment as
      soon as they thought was necessary.

PMID- 18637780
TI  - The Brisbane International Initiative: fostering leadership and international
      collaboration in primary care research.

PMID- 18637781
TI  - Research productivity in Australian general practice: what has changed since the
      1990s?
AB  - The Primary Health Care Research, Evaluation and Development (PHCRED) Strategy
      aims to improve Australia's output of high-quality research from primary care. We
      compared publication rates from general practice, medicine and surgery for the
      period 2000-2007, and found that general practice publications increased since
      1990-1999 from 1.0 to 3.0 publications per 1000 general practitioners per year.
      However, general practice publication rates have plateaued since 2000, and
      represent only 2%-5% of the equivalent rates for medicine and surgery. This
      finding suggests that more time and sustained investment in PHCRED are essential
      to see tangible outputs from funded research in general practice.

PMID- 18637782
TI  - Feasibility of conducting a primary prevention trial of low-dose aspirin for
      major adverse cardiovascular events in older people in Australia: results from
      the ASPirin in Reducing Events in the Elderly (ASPREE) pilot study.
AB  - AIM: To determine the feasibility of performing a large clinical trial of the use
      of aspirin for the primary prevention of cardiovascular disease in older
      participants--the ASPirin in Reducing Events in the Elderly (ASPREE) trial.
      DESIGN AND PARTICIPANTS: A randomised double-blind placebo-controlled pilot trial
      of 100 mg of enteric-coated aspirin tablets daily, in men and women aged 70 years
      and over who did not have overt cardiovascular disease, and who were followed for
      12 months. Participants were identified from the computer databases of general
      practitioners who were co-investigators in a previous trial. SETTING: The
      Melbourne metropolitan area between March 2003 and June 2005. MAIN OUTCOME
      MEASURES: The level of response to participation by GPs; the level of response
      from potential trial participants; the screening-to-randomisation rate to ensure
      the recruitment target could be achieved; and the retention of participants in
      the trial after 12 months. RESULTS: Forty-two GPs (23% of 180 mailed) expressed
      interest in participating in the pilot trial. Nineteen became co-investigators,
      of whom six were not required to meet recruitment targets. Letters were sent to
      2614 patients, of whom 243 were screened and 209 (86%) were randomly allocated to
      receive aspirin or placebo. At 12 months,192 (92%) returned for follow-up, and
      153 of these (80%) were still taking trial medication. There was a significant
      reduction in mean haemoglobin level in those taking aspirin. CONCLUSIONS: The
      recruitment strategy for ASPREE, based on methods developed for the conduct of a
      previous large-scale trial conducted in general practice, was successfully
      redeployed in this pilot study, with improved efficiency resulting from
      computerised database searching, telephone pre-screening, a simpler run-in phase
      and participant familiarity with the trial drug. We conclude that conducting
      ASPREE in Australian general practice with 18 000 participants is feasible. TRIAL
      REGISTRATION: International Standard Randomised Controlled Trial Number Register
      ISRCTN83772183.

PMID- 18637783
TI  - The promise and pitfalls of generalism in achieving the Alma-Ata vision of health
      for all.

PMID- 18637784
TI  - Getting back into the emergency department: diversifying general practice while
      relieving emergency medicine workforce shortages.
AB  - New medical graduates expect to work in an environment that allows scope for
      flexibility and change across a career in medicine. Recruitment to general
      practice is adversely affected by its perceived limited scope of practice.
      Training in procedural and hospital skills is not difficult to access for general
      practice trainees, but complex and inconsistent credentialling criteria and
      protectionist attitudes among some specialist colleges mean that many skilled
      general practitioners are unable to utilise the full range of their skills in
      clinical practice. The discipline of emergency medicine is also experiencing
      difficulty in recruiting trainees. The employment of skilled GPs in emergency
      departments (including metropolitan departments) could improve vocational
      satisfaction for GPs and emergency physicians, and possibly also improve patient
      outcomes and flow through the emergency department.

PMID- 18637785
TI  - Addiction and addiction medicine: exploring opportunities for the general
      practitioner.
AB  - Addiction medicine deals with problems arising from the use of psychoactive
      substances, and encompasses the disciplines of general practice and primary care,
      psychiatry, psychology, internal medicine, public health, pharmacology and
      sociology. Addiction is a chronic, relapsing illness that is difficult to cure.
      There are now effective, evidence-based interventions for the prevention and
      treatment of substance misuse disorders. Harm minimisation and treatment are more
      cost-effective than policing and supply-reduction methods of responding to
      substance misuse.

PMID- 18637786
TI  - Addressing general practice workforce shortages: policy options.
AB  - There is an ongoing shortage of general practitioners in Australia, accompanied
      by a decline in the popularity of general practice as a career choice. Many
      factors influence the career choice of junior doctors and medical students,
      including role models, the quality of clinical attachments during training,
      remuneration, and flexibility of training and working hours. Evidence-based
      strategies that could increase the number of doctors choosing general practice as
      a career include longer and higher-quality general practice attachments during
      medical school and the early postgraduate years, and emphasising the positive
      aspects of general practice, such as flexibility. General practice would become a
      more attractive choice if remuneration was in line with hospital specialties.

PMID- 18637787
TI  - Women's contribution to general practice: Medusa or Mother Teresa?

PMID- 18637788
TI  - Medical teaching in rural Australia: should we be concerned about the
      international medical graduate connection?
AB  - The two rural workforce strategies of rural clinical schools and deployment of
      international medical graduates (IMGs) geographically overlap in Australia's
      large expanse of under-served rural and remote areas. We used the Rural Clinical
      School of Western Australia (RCSWA) as a model to examine the relative numbers of
      IMG clinical academics, and the contribution of IMGs to rural clinical school
      development and education. IMGs have established six of 10 rural clinical school
      sites, maintained an academic presence, and continue to staff the RCSWA in high
      proportions. In a fragile rural work ecology, WA's IMGs are contributing to both
      meeting current workforce needs and the education of future rural doctors. The
      "double debt" Australia owes to IMGs, stemming from the rich cross-fertilisation
      of these two workforce strategies, should be acknowledged.

PMID- 18637789
TI  - Mapping of the ATP-binding domain of human fructosamine 3-kinase-related protein
      by affinity labelling with 5'-[p-(fluorosulfonyl)benzoyl]adenosine.
AB  - The modification of proteins by reducing sugars through the process of non
      enzymatic glycation is one of the principal mechanisms by which hyperglycaemia
      may precipitate the development of diabetic complications. Fn3K (fructosamine 3
      kinase) and Fn3KRP (Fn3K-related protein) are two recently discovered enzymes
      that may play roles in metabolizing early glycation products. However, although
      the activity of these enzymes towards various glycated substrates has been
      established, very little is known about their structure-function relationships or
      their respective mechanisms of action. Furthermore, their only structural
      similarities noted to date with members of other kinase families has been with
      the bacterial aminoglycoside kinases. In the present study, we employed affinity
      labelling with the ATP analogue FSBA {5'-p-[(fluorosulfonyl)benzoyl]adenosine} to
      probe the active-site topology of Fn3KRP as an example of this enigmatic family
      of kinases. FSBA was found to modify Fn3KRP at five distinct sites; four of these
      were predicted to be localized in close proximity to its ATP-binding site, based
      on alignments with the aminoglycoside kinase APH(3')-IIIa, and examination of its
      published tertiary structure. The results of the present studies provide evidence
      that Fn3KRP possesses an ATP-binding domain that is structurally related to that
      of both the aminoglycoside kinases and eukaryotic protein kinases.

PMID- 18637790
TI  - Conditional knockout of nucleolin in DT40 cells reveals the functional redundancy
      of its RNA-binding domains.
AB  - BACKGROUND INFORMATION: Nucleolin is a major nucleolar protein which is highly
      expressed in rapidly dividing cells and cancer cell lines. This protein is
      claimed to be multifunctional and could play a role in rRNA (ribosomal RNA)
      synthesis, as well as in cell division or response to cellular stresses.
      Therefore, how nucleolin influences cell proliferation remained elusive so far.
      RESULTS: We have generated conditional nucleolin-knockout cells using the chicken
      B lymphocyte cell line DT40. Our results indicate that nucleolin is absolutely
      required for the proliferation and for the survival of these cells. Depletion of
      nucleolin drastically inhibits rDNA (ribosomal DNA) transcription while only
      slightly affecting pre-rRNA processing. This inhibition is accompanied by
      modifications of the shape and the structure of the nucleolus. The analysis of
      mutants of nucleolin, which lack two or three RNA-binding domains, shows that
      these domains harbour redundant functions and that nucleolin's roles in
      transcription, rRNA maturation and nucleolar shape can be partially uncoupled.
      CONCLUSIONS: The function of nucleolin in ribosomal synthesis could account for
      its effect on cell division and survival, but this vital role does not seem to be
      linked to sequence-specific RNA binding.

PMID- 18637791
TI  - Carotenoid oxygenases involved in plant branching catalyse a highly specific
      conserved apocarotenoid cleavage reaction.
AB  - Recent studies with the high-tillering mutants in rice (Oryza sativa), the max
      (more axillary growth) mutants in Arabidopsis thaliana and the rms (ramosus)
      mutants in pea (Pisum sativum) have indicated the presence of a novel plant
      hormone that inhibits branching in an auxin-dependent manner. The synthesis of
      this inhibitor is initiated by the two CCDs [carotenoid-cleaving (di)oxygenases]
      OsCCD7/OsCCD8b, MAX3/MAX4 and RMS5/RMS1 in rice, Arabidopsis and pea
      respectively. MAX3 and MAX4 are thought to catalyse the successive cleavage of a
      carotenoid substrate yielding an apocarotenoid that, possibly after further
      modification, inhibits the outgrowth of axillary buds. To elucidate the substrate
      specificity of OsCCD8b, MAX4 and RMS1, we investigated their activities in vitro
      using naturally accumulated carotenoids and synthetic apocarotenoid substrates,
      and in vivo using carotenoid-accumulating Escherichia coli strains. The results
      obtained suggest that these enzymes are highly specific, converting the C27
      compounds beta-apo-10'-carotenal and its alcohol into beta-apo-13-carotenone in
      vitro. Our data suggest that the second cleavage step in the biosynthesis of the
      plant branching inhibitor is conserved in monocotyledonous and dicotyledonous
      species.

PMID- 18637792
TI  - Growth of beta(2)-microglobulin-related amyloid fibrils by non-esterified fatty
      acids at a neutral pH.
AB  - Abeta2M (beta(2)-microglobulin-related) amyloidosis is a frequent and serious
      complication in patients on long-term dialysis. Partial unfolding of beta2-m
      (beta(2)-microglobulin) may be essential to its assembly into Abeta2M amyloid
      fibrils in vivo. Although SDS around the critical micelle concentration induces
      partial unfolding of beta2-m to an alpha-helix-containing aggregation-prone
      amyloidogenic conformer and subsequent amyloid fibril formation in vitro, the
      biological molecules with similar activity under near-physiological conditions
      are still unknown. The effect of various NEFAs (non-esterified fatty acids),
      which are representative anionic amphipathic compounds in the circulation, on the
      growth of Abeta2M amyloid fibrils at a neutral pH was examined using fluorescence
      spectroscopy with thioflavin T, CD spectroscopy, and electron microscopy.
      Physiologically relevant concentrations of laurate, myristate, oleate, linoleate,
      and mixtures of palmitate, stearate, oleate and linoleate, induced the growth of
      fibrils at a neutral pH by partially unfolding the compact structure of beta2-m
      to an aggregation-prone amyloidogenic conformer. In the presence of human serum
      albumin, these NEFAs also induced the growth of fibrils when their concentrations
      exceeded the binding capacity of albumin, indicating that the unbound NEFAs
      rather than albumin-bound NEFAs induce the fibril growth reaction in vitro. These
      results suggest the involvement of NEFAs in the development of Abeta2M
      amyloidosis, and in the pathogenesis of Abeta2M amyloidosis.

PMID- 18637793
TI  - Structure-function analysis of plant aquaporin AtPIP2;1 gating by divalent
      cations and protons.
AB  - Water channel proteins, AQPs (aquaporins), of the PIP (plasma membrane intrinsic
      protein) subfamily, provide a means for fine and quick adjustments of the plant
      water status. A molecular model for gating of PIPs by cytosolic protons (H(+))
      and divalent cations was derived from the atomic structure of spinach SoPIP2;1
      (Spinacia oleracea PIP2;1) in an open- and a closed-pore conformation. In the
      present study, we produced the Arabidopsis AtPIP2;1 (Arabidopsis thaliana PIP2;1)
      homologue in Pichia pastoris, either WT (wild-type) or mutations at residues
      supposedly involved in gating. Stopped-flow spectrophotometric measurements
      showed that, upon reconstitution in proteoliposomes, all forms function as water
      channels. The first functional evidence for a direct gating of PIPs by divalent
      (bivalent) cations was obtained. In particular, cadmium and manganese were
      identified, in addition to calcium (Ca(2+)) and H(+) as potent inhibitors of WT
      AtPIP2;1. Our results further show that His(199), the previously identified site
      for H(+) sensing, but also N-terminal located Glu(31), and to a lesser extent
      Asp(28), are involved in both divalent-cation- and H(+)-mediated gating. In
      contrast, mutation of Arg(124) rendered AtPIP2;1 largely insensitive to Ca(2+)
      while remaining fully sensitive to H(+). The role of these residues in binding
      divalent cations and/or stabilizing the open or closed pore conformations is
      discussed.

PMID- 18637794
TI  - A calmodulin antagonist reveals a calmodulin-independent interdomain interaction
      essential for activation of inositol 1,4,5-trisphosphate receptors.
AB  - CaM (calmodulin) has been implicated in the regulation of IP3R [IP3 (inositol
      1,4,5-trisphosphate) receptors] and a recent report suggested that CaM tightly
      tethered to IP3R was essential for IP3R activation [Nadif Kasri, Torok, Galione,
      Garnham, Callewaert, Missiaen, Parys and De Smedt (2006) J. Biol. Chem. 281, 8332
      8338]. In the present study, we confirm that a CaM-binding peptide derived from
      MLCK (myosin light chain kinase) inhibits IP3-evoked Ca2+ release via all three
      IP3R subtypes. However,inhibition by MLCK peptide is not mimicked by other CaM
      antagonists that effectively block regulation of IP3R by CaM. Inhibition by MLCK
      peptide is rapid, fully reversible and occurs under conditions where there is no
      CaM associated with IP3R. MLCK peptide stimulates IP3 binding to IP3R1 and to its
      bacterially expressed N-terminal, but not after removal of the suppressor domain
      (residues 1-224).We suggest that MLCK peptide mimics a sequence within the
      suppressor domain that is similar to a1-8-14 CaM-binding motif. The peptide may
      thereby unzip an interdomain interaction that is essential for IP3R activation.
      We conclude that CaM is not essential for IP3R activation, and that MLCK peptide
      is a selective antagonist of the IP3R that binds directly to the N-terminal to
      uncouple IP3 binding from channel gating. The results of the present study
      highlight the importance of the suppressor domain in IP3R activation and suggest
      that MLCK peptide may provide a route to novel non-competitive antagonists of
      IP3R.

PMID- 18637795
TI  - No structural cerebral differences between children with a history of bacterial
      meningitis and healthy siblings.
AB  - AIM: After bacterial meningitis, about one-third of children develops academic
      and/or behavioural limitations. The aim of our study was to search for structural
      differences in the brain, with a special focus on the hippocampus, between
      childhood survivors of bacterial meningitis with and without academic and/or
      behavioural limitations and healthy siblings. PATIENTS AND METHODS: A selection
      of a cohort, compiled in an earlier performed retrospective study, was used in
      this case-control study. Magnetic Resonance Imaging scans of the brain were
      performed in 43 post-meningitis children, of whom 18 had learning and/or
      behavioural limitations and 25 had no problems, and 18 controls. Voxel-based
      morphometry investigated the brain for structural changes. Hippocampal volume and
      lateral ventricle width were measured. RESULTS: No structural differences between
      the groups, in any area of the brain, were found. There were no significant
      differences in hippocampal volume or lateral ventricle width. The group with
      limitations had three children with a right hippocampal volume smaller than two
      standard deviations below the mean of the control group. CONCLUSION: Despite
      hippocampus lesions found in experimental studies, we found no anatomical
      differences of the brain or hippocampus related to bacterial meningitis in
      children, nor to the academic and/or behavioural limitations seen after bacterial
      meningitis.

PMID- 18637798
TI  - Analyses of volatile organic compounds from human skin.
AB  - BACKGROUND: Human skin emits a variety of volatile metabolites, many of them
      odorous. Much previous work has focused upon chemical structure and biogenesis of
      metabolites produced in the axillae (underarms), which are a primary source of
      human body odour. Nonaxillary skin also harbours volatile metabolites, possibly
      with different biological origins than axillary odorants. OBJECTIVES: To take
      inventory of the volatile organic compounds (VOCs) from the upper back and
      forearm skin, and assess their relative quantitative variation across 25 healthy
      subjects. METHODS: Two complementary sampling techniques were used to obtain
      comprehensive VOC profiles, viz., solid-phase microextraction and solvent
      extraction. Analyses were performed using both gas chromatography/mass
      spectrometry and gas chromatography with flame photometric detection. RESULTS:
      Nearly 100 compounds were identified, some of which varied with age. The VOC
      profiles of the upper back and forearm within a subject were, for the most part,
      similar, although there were notable differences. CONCLUSIONS: The natural
      variation in nonaxillary skin odorants described in this study provides a
      baseline of compounds we have identified from both endogenous and exogenous
      sources. Although complex, the profiles of volatile constituents suggest that the
      two body locations share a considerable number of compounds, but both
      quantitative and qualitative differences are present. In addition, quantitative
      changes due to ageing are also present. These data may provide future
      investigators of skin VOCs with a baseline against which any abnormalities can be
      viewed in searching for biomarkers of skin diseases.

PMID- 18637799
TI  - Methylene blue-photoinactivated plasma versus quarantine fresh frozen plasma in
      thrombotic thrombocytopenic purpura: a multicentric, prospective cohort study.
AB  - Plasma exchange (PE) with plasma infusion is the treatment of choice for
      thrombotic thrombocytopenic purpura (TTP) but doubts remain as to whether all
      kinds of plasma are equally effective. A multicentric cohort study was conducted
      to compare methylene blue-photoinactivated plasma (MBPIP) with quarantine fresh
      frozen plasma (qFFP) in the treatment of TTP. One hundred and two episodes of
      idiopathic TTP were included; MBPIP was used in 63 and qFFP in 39. The treatment
      schedule consisted of daily PE and costicosteroids, and the main end-point was
      remission status on day 8. Patients treated with MBPIP required more PEs (median:
      11 vs. 5, P = 0.002) and a larger volume of plasma (median: 485 ml/kg vs. 216
      ml/kg, P = 0.007) to achieve a remission, and presented more recrudescences while
      on PE therapy (29 of 63 vs. 8 of 39, P = 0.02) than those receiving qFFP. After
      adjustment for possible confounding factors, the use of MBPIP was associated with
      a lower likelihood of remission on day 8 [Odds ratio (OR): 0.17; 95% confidence
      interval (CI): 0.06-0.47] and a higher risk of recrudescence while on treatment
      (OR: 4.2; 95% CI: 1.6-10.8). In conclusion, MBPIP is less effective than qFFP in
      the treatment of TTP.

PMID- 18637800
TI  - Recent advances in the understanding of inherited sideroblastic anaemia.
AB  - Sideroblastic anaemia includes a heterogeneous group of rare conditions,
      characterized by decreased haem synthesis and mitochondrial iron overload, which
      are diagnosed by the presence of ringed sideroblasts in the bone marrow aspirate.
      The most frequent form is X-linked sideroblastic anaemia, caused by mutations of
      delta-aminolevulinic acid synthase 2 (ALAS2), the enzyme that catalyses the first
      and regulatory step of haem synthesis in erythroid precursors and is post
      transcriptionally controlled by the iron regulatory proteins. Impaired haem
      production causes variable degrees of anaemia and mitochondrial iron accumulation
      as ringed sideroblasts. The heterogeneity and complexity of sideroblastic anaemia
      is explained by an increasing number of recognized molecular defects. New forms
      have been recognized as being linked to the deficient function of mitochondrial
      proteins involved in iron-sulphur cluster biogenesis, such as ABCB7 and GLRX5,
      which are extremely rare but represent important biological models. Local
      mitochondrial iron overload is present in all sideroblastic anaemias, whereas
      systemic iron overload occurs only in the forms because of primary or secondary
      deficiency of ALAS2.

PMID- 18637801
TI  - Interleukin-10 protects against blood-induced joint damage.
AB  - Despite prophylactic treatment, haemophilia patients suffer from spontaneous
      joint bleeds, which lead to severe joint damage. Also after joint trauma, an
      intra-articular haemorrhage can add to joint damage over time. This study
      evaluated interleukin 10 (IL-10) in the search for possible interventions to
      prevent or limit the damaging effects of joint bleeds. Human articular cartilage
      tissue explants were cultured in the presence or absence of 50% v/v blood (or its
      cellular components) for 4 d (the expected blood load in vivo after a joint
      haemorrhage), followed by a recovery period of 12 d. Pharmacological dosages of
      IL-10 reached during treatment (1 or 10 ng/ml) were added. Additionally,
      cartilage and synovial tissue obtained from joints with end-stage haemophilic
      arthropathy (HA) were cultured in the presence of IL-10 (10 ng/ml). IL-10
      protected cartilage from the damaging effects of blood exposure, measured by its
      effects on proteoglycan turnover. In addition, IL-10 beneficially influenced
      cartilage from patients with HA and reduced the production of the inflammatory
      cytokines IL-1beta and tumour necrosis factor-alpha by haemophilic synovial
      tissue. Taken together, although effects were obtained in vitro, IL-10 protects
      against blood-induced joint damage and might be further evaluated as candidate in
      treatment of tissue damaging effects of joint haemorrhages.

PMID- 18637802
TI  - Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and
      clinical features.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an acute, rare, life-threatening
      disorder. This report presents the South East (SE) England registry for TTP, from
      April 2002 to December 2006, which included 176 patients and 236 acute episodes;
      75% of patients were female and 25% were male, overall median age at presentation
      was 42 years. Mortality was 8.5%, most cases died before treatment was
      instigated. The main ethnic groups were Caucasian (64%) and Afro Caribbean (27%).
      Seventy-seven percent of cases were idiopathic, 5% were congenital and the
      remaining cases had a defined precipitant. Neurological features were the most
      prevalent, but cardiac involvement accounted for 42% of presenting features. The
      overall median number of plasma exchanges (PEXs) to remission was 15; between
      April 2002 and December 2003, the median number of PEXs was 19 and it was 12
      between January 2004 and December 2006 (P < 0.0001). In the latter period,
      adjuvant therapies were reduced, but Rituximab was increased. ADAMTS 13 (a
      disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)
      activity was <10% in 74% and 95% of these cases had positive IgG antibodies to
      ADAMTS 13. Renal impairment and delayed normalisation of platelet count were the
      main differences between idiopathic and secondary TTP.

PMID- 18637803
TI  - Central retinal vein occlusion heralding the relapse of haematodermic neoplasm.

PMID- 18637804
TI  - Evaluation of minimal residual disease in multiple myeloma patients by
      fluorescent-polymerase chain reaction: the prognostic impact of achieving
      molecular response.
AB  - This study aimed to standardize a simple molecular method for evaluating the
      response to treatment in multiple myeloma (MM) patients after high dose
      chemotherapy. Fifty three patients enrolled in the GEM2000 protocol were studied
      for minimal residual disease (MRD) using both fluorescent-polymerase chain
      reaction (F-PCR) and flow cytometry. Most patients had achieved complete
      remission or very good response after autologous stem cell transplantation. The
      molecular analysis of immunoglobulin gene rearrangements at diagnosis and during
      the follow-up was carried out by F-PCR according to the Biomed-2 protocols. F-PCR
      could be used in 91% of the patients and the results were similar to flow
      cytometry. F-PCR was able to identify a group of patients with a better prognosis
      [progression-free survival (PFS) 67.86% in patients with negative F-PCR vs. 28%;
      P = 0.001], even amongst patients who achieved a complete response with negative
      immunofixation (PFS 75% vs. 25%; P = 0.002). Multivariate analysis identified the
      F-PCR result as the only variable to show a prognostic value when PFS was
      analysed. F-PCR of DHJ and light chain rearrangements of immunoglobulin genes is
      a feasible method for evaluating MRD in MM patients after intensive therapy.
      Achieving molecular response by F-PCR shows prognostic value.

PMID- 18637805
TI  - Naturally occurring CD4+ CD25+ regulatory T cells modulate the haematopoietic
      potential of human stem cells in vitro.

PMID- 18637806
TI  - Characterization of the bone marrow immunofluorescence test in childhood
      autoimmune neutropenia.
AB  - The bone marrow immunofluorescenece test (BMIFT) demonstrates autoantibodies to
      granulocytes and their precursors on fresh-frozen bone marrow slides. It may be
      used to differentiate childhood autoimmune neutropenia (AIN) from other causes of
      childhood neutropenia, even when circulating neutrophil counts are low. We sought
      to characterize the diagnostic utility of the BMIFT in childhood AIN. All BMIFT
      requests for investigation of children with neutropenia between January 1998 and
      May 2007 were reviewed. Patients were classified as AIN or nonautoimmune causes.
      Baseline demographic data, results of BMIFT, granulocyte immunofluorescence
      testing and bone marrow findings were collected from clinical records and the
      institutional laboratory database. Seventy-six children had BMIFT performed for
      investigation of neutropenia. There were 45 patients diagnosed with AIN, 28 with
      nonimmune neutropenia and three failed tests. The median age of children with AIN
      was 1.2 years (range 0.3-15.3), compared with 3.6 years (range 0.1-15.7) in the
      nonautoimmune group. The median neutrophil count in AIN was 0.3 x 10(9)/l (0.9 x
      10(9)/l in nonautoimmune). BMIFT was positive in 24 of 45 patients with AIN and 0
      of 28 with nonautoimmune neutropenia (sensitivity 53%, specificity 100%, positive
      predictive value (PPV) 100%, negative predictive value 57%). Ten patients had
      other autoimmune diatheses at diagnosis. The BMIFT is a simple, highly specific
      test with excellent PPV and thus is a clinically useful test to confirm AIN in
      children.

PMID- 18637807
TI  - Comparative analysis of G-CSFR and GM-CSFR expressions on CD34+ cells in patients
      with aplastic anemia and myelodysplastic syndrome.
AB  - The aim of this article was to explore the pathogenetic differences, as well as
      to provide a new way for the differential diagnosis of these two diseases by
      comparative analysis of CD(34)(+) cells numbers and their surface expression of
      granulocyte colony-stimulating factor receptor (G-CSFR) and granulocyte
      macrophage colony-stimulating factor receptor (GM-CSFR) in patients with aplastic
      anemia (AA) and myelodysplastic syndrome (MDS). Twenty-seven patients with AA, 45
      patients with MDS, and 20 normal controls were enrolled in this study. The ratio
      of CD(34)(+) cells and their surface expression of G-CSFR and GM-CSFR were
      detected by flow cytometry (FCM). The ratio of CD(34)(+) cells in BMMNC of AA,
      MDS patients and controls were 0.2438 +/- 0.1129%, 2.1677 +/- 1.1345% and 1.0792
      +/- 0.3221%, respectively. Compared with normal controls as well as MDS patients,
      the ratio of CD(34)(+) cells in BMMNC of AA was significantly reduced (P < 0.05).
      The ratio of CD(34)(+) cells in MDS was significantly elevated than controls (P <
      0.05). The ratio of CD(34)(+) cells in BMMNC of MDS-RA and MDS-RAEB patients were
      1.2821 +/- 0.4658% and 3.7729 +/- 2.3360%, respectively. Compared with normal
      controls and MDS-RA patients, the ratio of CD(34)(+) cells in MDS-RAEB was
      significantly elevated (P < 0.05). The ratio of CD(34)(+) cells in MDS-RA was
      significantly elevated than AA patients (P < 0.05). The surface expression of G
      CSFR on CD(34)(+) cells of AA, MDS patients and controls were 34.402 +/-
      21.8357%, 26.376 +/- 15.2895% and 21.443 +/- 7.4465%, respectively. The surface
      expression of G-CSFR on CD(34)(+) cells of MDS-RA and MDS-RAEB patients were
      22.788 +/- 14.7628% and 30.682 +/- 15.5346%. The surface expression of GM-CSFR on
      CD(34)(+) cells of AA, MDS patients and controls were 6.5961 +/- 4.4322%, 18.2737
      +/- 10.9841% and 4.2753 +/- 2.6249%, respectively. Compared with AA and controls,
      the expression of GM-CSFR in MDS patients was significantly elevated (P < 0.05).
      The surface expression of GM-CSFR on CD(34)(+) cells of MDS-RA and MDS-RAEB
      patients were 16.1625 +/- 6.9487% and 22.1003 +/- 14.2983%. In AA patients, the
      ratio of CD(34)(+) cells in BMMNC less than 0.1% accounts for 75% (6/8) SAA
      patients, compared with 10.55% (2/19) in CAA (P < 0.05). The detection of
      CD(34)(+) cells and their surface expression of granulocyte (macrophage) colony
      stimulating factor receptors G (M)-CSFR in AA and MDS are helpful in the
      differential diagnosis or prognosis of these two disorders.

PMID- 18637808
TI  - Differential phosphoproteome profiling reveals a functional role for VASP in
      Helicobacter pylori-induced cytoskeleton turnover in gastric epithelial cells.
AB  - Infection with Helicobacter pylori induces various gastric diseases, including
      ulceration, gastritis and neoplasia. As H. pylori-induced cellular mechanisms
      leading to these disease states are widely unclear, we analysed the
      phosphoproteome of H. pylori-infected gastric epithelial cells. Phosphoproteins
      from infected cells were enriched using affinity columns and analysed by two
      dimensional gel electrophoresis and mass spectrometry. Eleven novel
      phosphoproteins that showed differentially regulated phosphorylation levels
      during H. pylori infection were identified. Interestingly, the identified
      proteins were actin-binding, transport and folding, RNA/DNA-binding or cancer
      associated proteins. We analysed functions of one identified H. pylori-regulated
      candidate, the vasodilator-stimulated phosphoprotein (VASP). H. pylori induced
      VASP phosphorylation at residues Ser157, Ser239 and Thr278, which was enhanced by
      the bacterial oncogene cytotoxin-associated gene A. Overexpression of a
      phosphorylation-resistant VASP mutant efficiently blocked host cell elongation.
      We identified cGMP-dependent protein kinase G-mediated Ser239 and Thr278
      phosphorylation of VASP as a crucial event in H. pylori-dependent host cell
      elongation. These results suggest that phosphorylated VASP could be a novel
      target candidate for therapeutic intervention in H. pylori-related gastric
      diseases.

PMID- 18637809
TI  - Technical external quality assessment for SurePath stained liquid-based cytology
      gynaecological cervical samples using control material--a novel approach.
AB  - AIMS AND OBJECTIVE: The Technical External Quality Assessment Scheme (TEQA)
      introduced in Wales is based on NHSCSP publication No 19 [External Quality
      Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical
      Cytology] which sets out the policies and standard operating procedures for the
      TEQA of Papanicolaou staining of gynaecological cervical samples. As part of a
      development plan for the TEQA scheme in Wales, the use of a control sample was
      introduced to the assessment process - a common control sample can provide a
      consistent assessment parameter independent of the recommended slide selection
      process [External Quality Assessment Scheme for the Evaluation of Papanicolaou
      Staining in Cervical Cytology, NHSCSP Publication No 19, February 2004] enabling
      direct comparison of staining standards for laboratories within the region; this
      counters selection variation bias, establishing a process that may be more
      representative of routine staining results. METHODS: A cervical sample was
      selected in line with the criteria described in publication 19 [External Quality
      Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical
      Cytology, NHSCSP Publication No 19, February 2004]. Thirteen slides were prepared
      by the scheme facilitator from this anonymized sample. These control slides were
      subsequently 'fixed' but not stained, then distributed to the laboratories
      participating in the TEQA scheme. The slides were stained using their standard
      regime, then returned to the facilitator for assessment. The slides showed
      consistent staining with no significant inter-laboratory variation, however, the
      eosinophilic stained components exhibited an artificial colouration, which
      slightly altered the expected stained appearance; this was thought to be due to
      'cross-reactivity' of the spray fixative with the preserving agent. To address
      this artefact, a further development of control procedures was devised utilizing
      a pooled control sample procedure. Residual material from a number of similar
      samples was pooled and distributed in aliquots to participant laboratories for
      standard processing and staining; the completed slides were returned to the
      scheme facilitator for assessment. RESULTS: The pooled sample slides were
      assessed at the next scheduled quarterly TEQA assessment. The overall scoring for
      these samples produced an acceptable level of Papanicolaou staining for 12 of the
      laboratories - only one laboratory produced a marginal score. The artefactual
      presentation of eosinophilia was not seen. DISCUSSION/CONCLUSION: This method of
      producing control material establishes consistency in the TEQA comparative
      assessment process, counters selection bias and reduces the time demands
      associated with slide selection. It may also prove useful in identifying
      technical problems within laboratories during sample preparation prior to or
      during staining, including equipment or process faults. This technique is now
      well established locally as an enhancement of the current TEQA scheme for the
      assessment of slide staining. We feel that this enhancement could be incorporated
      as a new initiative in the current National TEQA scheme as a complement to the
      established selection process.

PMID- 18637810
TI  - Low-grade fibromyxoid sarcoma is difficult to diagnose by fine needle aspiration
      cytology: a cytomorphological study of eight cases.
AB  - BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon neoplasm with
      bland morphology and an indolent clinical course, although metastases may develop
      in approximately 5-10% of the cases. The diagnosis of LGFMS can be difficult to
      render from fine needle aspiration cytology (FNAC) alone because of morphological
      overlap with other spindle cell and myxoid lesions. OBJECTIVE: To determine
      cytological criteria for LGFMS by reviewing FNAC aspirates in eight cases and to
      compare the findings with those in subsequent histological sections. METHODS:
      FNAC slides were reviewed from eight patients with subsequently excised tumours
      diagnosed as LGFMS. Of these patients, six also had core needle biopsies (CNB).
      Cytogenetic and/or molecular analysis was carried on all tumours. RESULTS: The
      patients were six men and two women ranging in age from 26 to 78 years. Tumours
      arose in the deep soft tissues of the thigh (n = 5), shoulder girdle (n = 1) or
      upper arm (n = 1) and one in the subcutaneous tissue of the abdominal wall.
      Cytological features included clusters of bland spindle and round/polygonal cells
      embedded in a collagenous and myxoid matrix along with dissociated, uniform or
      slightly/moderately pleomorphic spindle cells, bare nuclei and fragments of
      collagen and myxoid tissue in varying proportions. Unequivocal sarcoma was
      diagnosed in two aspirates, but mitoses were absent in all cases. In three cases,
      the diagnosis was inconclusive with regard to benignity or malignancy, while
      three were erroneously diagnosed as benign spindle cell lesions. Although the
      diagnosis was suggested on three of six CNB, these presented similar diagnostic
      problems. CONCLUSIONS: There were no cytomorphological findings in FNAC to allow
      for a clear cut separation of LGFMS from other spindle cell or myxoid lesions,
      but high-grade sarcoma could be excluded. Surgical (incisional or excisional)
      biopsy or, alternatively, examination of RT-PCR for the FUS/CREB3L or FUS/CREB3L1
      fusion transcripts may be necessary to obtain a correct diagnosis.

PMID- 18637811
TI  - A giant atypical hidradenoma on the neck.

PMID- 18637812
TI  - Angiosarcoma clinically resembling morpheaform basal cell carcinoma.

PMID- 18637813
TI  - Using the smallest skin excision without dog-ear formations: utilizing
      histopathology on the face.

PMID- 18637814
TI  - Reversal of laser-induced hypopigmentation with a narrow-band UV-B light source
      in a patient with skin type VI.

PMID- 18637815
TI  - Ala nasal reconstruction in trigeminal trophic syndrome.

PMID- 18637816
TI  - Differences in dermoscopic images from nonpolarized dermoscope and polarized
      dermoscope influence the diagnostic accuracy and confidence level: a pilot study.
AB  - BACKGROUND: Studies have demonstrated differences in colors and dermoscopic
      structures observed with polarized dermoscopes (PDs) and nonpolarized dermoscopes
      (NPDs). OBJECTIVE: The objective was to evaluate whether diagnosis and diagnostic
      confidence changes when viewing dermoscopic images from NPDs and PDs. METHODS: A
      total of 100 dermatologists participated in the study. Twenty-five pigmented
      lesions were shown in the study, consisting of 7 seborrheic keratoses (SK), 3
      basal cell carcinomas, 2 atypical nevi, 5 malignant melanomas (MM), 3
      dermatofibromas, 3 blue nevi, and 2 hemangiomas. Two images of each lesion (one
      NPD and one PD) were included. The McNemar test and paired t-test were used for
      the statistical analysis. RESULTS: Ninety-one participants completed the study.
      Significant differences in the diagnoses were observed for the SK, atypical
      nevus, and MM images. Seventy-five percent and 59% of the final participants
      correctly diagnosed SK when presented with the NPD and PD images, respectively.
      For MM, 23 and 34% made the correct diagnoses with the NPD and PD images,
      respectively. CONCLUSIONS: Viewing lesions with NPD versus PD can affect the
      diagnosis and diagnostic confidence of physicians that are novices with
      dermoscopy. Further studies including physicians at different expertise levels
      and a larger sample of lesions are needed to further explore the differences.

PMID- 18637817
TI  - Treatment of digital mucous cysts with percutaneous sclerotherapy using
      polidocanol.

PMID- 18637818
TI  - The bilobed transposition flap for single-staged repair of large surgical defects
      involving the nasal ala.

PMID- 18637819
TI  - Stage-specific activation of MIG-17/ADAMTS controls cell migration in
      Caenorhabditis elegans.
AB  - The activation of ADAMTS (a disintegrin and metalloprotease with thrombospondin
      motifs) family proteases depends on removal of the prodomain. Although several
      studies suggest that ADAMTS activities play roles in development, homeostasis and
      disease, it remains unclear when and where the enzymes are activated in vivo. MIG
      17, a Caenorhabditis elegans glycoprotein belonging to the ADAMTS family, is
      secreted from the body wall muscle cells and localizes to the gonadal basement
      membrane to control the migration of gonadal distal tip cells. Here, we developed
      a monoclonal antibody that recognizes the N-terminal neo-epitope of the activated
      MIG-17. In western blotting, the antibody specifically detected the activated
      form, the signal for which dramatically increased during the third and fourth
      larval stages, when MIG-17 is required to direct distal tip cell migration. In in
      situ staining, the monoclonal antibody recognized the activated form in the
      basement membrane, whereas it failed to detect a processing-resistant mutant form
      localized to the basement membrane. MIG-17 was activated in the basement
      membranes of the muscle, intestine and gonad in the third larval stage, and
      downregulated in nongonadal basement membranes in young adults and in gonadal
      basement membranes in older adults. Thus, the activation of MIG-17 is regulated
      in a spatiotemporal manner during C. elegans development. This is the first
      report demonstrating the regulated activation of an ADAMTS protein in vivo. Our
      results suggest that monoclonal antibodies against neo-epitopes have potential as
      powerful tools for detecting activation of ADAMTSs during development and in
      disease pathogenesis.

PMID- 18637820
TI  - Thermal unfolding and aggregation of actin.
AB  - Actin is one of the most abundant proteins in nature. It is found in all
      eukaryotes and plays a fundamental role in many diverse and dynamic cellular
      processes. Also, actin is one of the most ubiquitous proteins because actin-like
      proteins have recently been identified in bacteria. Actin filament (F-actin) is a
      highly dynamic structure that can exist in different conformational states, and
      transitions between these states may be important in cytoskeletal dynamics and
      cell motility. These transitions can be modulated by various factors causing the
      stabilization or destabilization of actin filaments. In this review, we look at
      actin stabilization and destabilization as expressed by changes in the thermal
      stability of actin; specifically, we summarize and analyze the existing data on
      the thermal unfolding of actin as measured by differential scanning calorimetry.
      We also analyze in vitro data on the heat-induced aggregation of actin, the
      process that normally accompanies actin thermal denaturation. In this respect, we
      focus on the effects of small heat shock proteins, which can prevent the
      aggregation of thermally denatured actin with no effect on actin thermal
      unfolding. As a result, we have proposed a mechanism describing the thermal
      denaturation and aggregation of F-actin. This mechanism explains some of the
      special features of the thermal unfolding of actin filaments, including the
      effects of their stabilization and destabilization; it can also explain how small
      heat shock proteins protect the actin cytoskeleton from damage caused by the
      accumulation of large insoluble aggregates under heat shock conditions.

PMID- 18637821
TI  - Variability in duration of follow up may bias the conclusions of cohort studies
      of patients with patent foramen ovale.
AB  - Closure of patent foramen ovale (PFO) is expected to prevent paradoxical emboli.
      In the absence of randomized trials, its efficacy has been assessed by comparing
      uncontrolled cohort studies of medically treated patients with those treated by
      PFO closure. The objective of this study was to highlight a confounder of such
      studies, namely, the variability in the duration of follow-up. We searched the
      literature for cohort studies of patients with ischaemic strokes, including those
      with PFO. During the first year of follow-up, recurrence hazards in patients
      younger than 55 years were 1-4% in those with any ischaemic stroke, 1-6% in
      medically treated patients with PFO and 0-5% in those after PFO closure. In most
      studies, the recurrence hazards were highest immediately after the index stroke
      and declined thereafter. Still, hazards were commonly reported in terms of annual
      averages over a wide range of follow-up periods for the various cohort studies,
      thereby ignoring the possibility that the duration of the follow-up may in and of
      itself affect the derived average recurrence hazards. A disregard of the time
      variance of stroke recurrence may confound the conclusions from comparisons
      between uncontrolled studies of patients with stroke and PFO.

PMID- 18637822
TI  - Body mass index does not change before Parkinson's disease onset.
AB  - BACKGROUND AND PURPOSE: Previous studies on the association between Parkinson's
      disease (PD) and body mass index (BMI) have reported conflicting results. We
      investigated the relationship between PD and BMI by a case-control study.
      METHODS: PD patients were randomly matched to healthy individuals by sex and age.
      BMI distribution in cases has been compared with BMI of controls and odd ratios
      (ORs) with 95% CI were calculated. RESULTS: We included 318 PD patients and 318
      controls. We observed no association between PD and BMI. BMI distribution in
      cases and controls was similar also when we adjusted for diabetes,
      hypercholesterolemia and the time elapsed between PD onset and the interview (OR
      = 0.99; CI = 0.94-1.03; P = 0.51). CONCLUSIONS: These results did not confirm the
      previously reported association between PD and BMI. Population characteristics
      and methodological issues may partially account for the differences observed
      between the present study and the others.

PMID- 18637823
TI  - Aseptic meningitis and encephalitis because of herpesviruses and enteroviruses in
      an immunocompetent adult population.
AB  - BACKGROUND AND AIM: Human herpesviruses (HHVs) and enteroviruses (EVs) are the
      major causative agents of CNS viral infections. The aim of the study was to
      identify the etiology and determine the frequency of aseptic meningitis and
      encephalitis due to HHVs and EVs in an immunocompetent adult population. METHODS:
      Eighty-one patients (ages >or=15) with aseptic meningitis or encephalitis treated
      in the Infectious Diseases Hospital of Thessaloniki, Greece, during 2003-2006,
      were included in the study. Polymerase chain reaction for detection of herpes-
      and enterovirus genome direct in cerebrospinal fluid samples was performed.
      RESULTS: Based on clinical and laboratory data, 36/81 patients had meningitis and
      45/81 had encephalitis. Etiology was defined in 11 patients (31%) with aseptic
      meningitis. EVs were the major causative agents (8/36, 22%), followed by
      varicella zoster virus (2/36, 5%) and herpes simplex virus-2 (HSV-2) (1/36, 3%).
      Etiology was identified in 8 of 45 (18%) patients with encephalitis, EV (4/45,
      9%) and HSV-1 (4/45, 9%) being the most common pathogens. CONCLUSION:
      Enteroviruses are the most common cause of adult aseptic meningitis and together
      with HSV-1 the main causes of encephalitis.

PMID- 18637824
TI  - Size of PFO and amount of microembolic signals in patients with ischaemic stroke
      or TIA.
AB  - BACKGROUND AND PURPOSE: The inter-relation between the size of patent foramen
      ovale (PFO) by transesophageal echocardiography (TEE) and the amount of
      microembolic signals (MES) on transcranial doppler (TCD) is still not determined.
      METHODS: The study group comprised of 104 patients with first-ever ischaemic
      stroke or transient ischemic attack (TIA). Three groups were formed according to
      the amount of MES on TCD: a small amount of MES (0-10 MES); a moderate amount of
      MES (countable MES higher than 10); and multiple MES. RESULTS: According to TEE,
      there were 52 patients (50%) with a small PFO, 37 patients (35.6%) with a
      moderate PFO, and 15 patients (14.4%) with a large PFO. There were 48 patients
      (46.1%) with a small amount of MES, 34 patients (32.7%) with a moderate amount of
      MES, and 22 patients (21.1%) with multiple MES on TCD. A strong relationship
      between the size of the PFO on TEE and the amount of MES on contrast transcranial
      Doppler was found (P < 0.0001), such that the larger the PFO on TEE, the greater
      the amount of MES on TCD. CONCLUSIONS: There is a high correlation between the
      size of the PFO on TEE and the amount of MES on TCD in stroke and TIA patients.

PMID- 18637825
TI  - Higher severity of frontal periventricular white matter and basal ganglia
      hyperintensities in first-ever lacunar stroke with multiple silent lacunes.
AB  - BACKGROUND AND PURPOSE: We investigated whether patients with a lacunar infarct
      (LI) syndrome exhibiting unique LI or multiple LI on magnetic resonance imaging
      (MRI) examinations differed in terms of topography and severity of white matter
      hyperintensities (WMH) ratings. METHODS: Forty consecutive patients with a first
      ever acute LI, who presented a lacunar syndrome according to Miller-Fisher's
      classification were recruited and were classified into a group presenting
      isolated LI on MRI (n = 17) or multiple LI (n = 23). RESULTS: Despite equivalent
      demographic, clinical and cognitive characteristics, patients with multiple LI
      had increased ratings of WMH in frontal, occipital and subcortical regions. No
      significant correlations could be evidenced between the number of LI and WMH
      ratings. CONCLUSIONS: Present findings provide support to previous hypothesis
      considering single and multiple LI MRI presentations of lacunar infarct patients
      as distinct entities.

PMID- 18637826
TI  - Motor changes during sertraline treatment in depressed patients with Parkinson's
      disease*.
AB  - BACKGROUND: Pharmacological interventions to treat depressive symptoms associated
      with Parkinson's disease (PD) are limited. Whether selective serotonine re-uptake
      inhibitors increase parkinsonism or have clinically significant interactions with
      antiparkinsonian drugs is unresolved. PURPOSE: We used a naturalistic approach to
      prospectively investigate the long-term effects on motor status of adding
      sertraline in a large sample of community-dwelling PD patients with depressive
      symptoms. METHODS: Main outcome measure was the motor part of the Unified PD
      Rating Scale (UPDRS) at baseline and at 1-, 3-, and 6-month follow-up. Secondary
      measures were the change in antiparkinsonian drugs expressed as total levodopa
      equivalent dose and the scores of the Hospital Anxiety and Depression Scale
      (HADS). Of the 374 patients included, 310 (82%) completed the study. RESULTS:
      Treatment with sertraline (mean dose 66.0 +/- 29.8 mg) resulted in improvement in
      all UPDRS domains along with a significant decrease of the HADS scores. A modest
      but significant increase of the total dose of levodopa, without significant
      change of total levodopa equivalent dose, was observed. Almost 8% of patients
      discontinued medication for adverse events, mainly related to the
      gastrointestinal system. CONCLUSIONS: Although worsening of tremor was observed
      in some patients, active management of depression with sertraline appears to have
      a positive impact on parkinsonism.

PMID- 18637827
TI  - Cerebrospinal fluid tau and amyloid beta42 protein in patients with myotonic
      dystrophy type 1.
AB  - BACKGROUND: Myotonic dystrophy type 1 (DM1) is associated with brain morphology
      changes including neurofibrillary degeneration. METHODS: We have examined
      cerebrospinal fluid (CSF) markers indicative of neuronal degeneration and
      amyloidogenesis; total tau (T-tau), phosphorylated tau (P-tau) and beta amyloid 1
      42 (Abeta42), in 32 patients with DM1. RESULTS AND CONCLUSIONS: Associations
      between CSF markers and CTG repeat expansion size, brain MRI findings, and
      neuropsychological test results were analysed. As compared with matched controls
      Abeta42 was significantly decreased (P = 0.001), whilst levels of T-tau were
      increased (P < 0.001). No difference was found between measures considering P-tau
      levels. At present the clinical implications of these findings is unclear,
      because of an overlap between CSF values of DM1 patients and healthy controls,
      but also regarding modest associations between CSF markers and other measures.
      However notably, the Tau pathology, as seen in DM1, differs from Alzheimers
      disease, considering the lack of increased levels of P-tau.

PMID- 18637828
TI  - Eicosapentaenoic and docosahexaenoic acids are not anticonvulsant or
      neuroprotective in acute mouse seizure models.
AB  - Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), or vegetable oil
      (control) were added to standard rodent chow (6 g/kg) and fed to mice ad lib for
      4 weeks to determine if polyunsaturated fatty acids (PUFA) are anticonvulsant or
      neuroprotective in mice. The seizure susceptibility of these mice was compared
      using the fluorothyl, pentylenetetrazole (PTZ), 6 Hz, and kainate models. We
      found that PUFA feeding significantly altered the fatty acid profile in both
      plasma and brain, but did not change seizure thresholds in the fluorothyl, PTZ,
      or 6 Hz models nor did it significantly alter seizure behavior or hippocampal
      damage following kainate injection. In conclusion, DHA or EPA feeding did not
      show anticonvulsant or neuroprotective activity in four acute seizure models.
      Chronic seizure models remain to be examined.

PMID- 18637829
TI  - Focal decreases of cortical GABAA receptor binding remote from the primary
      seizure focus: what do they indicate?
AB  - PURPOSE: To determine the electroclinical significance and histopathological
      correlates of cortical gamma-aminobutyric acid(A)(GABA(A)) receptor abnormalities
      detected in and remote from human neocortical epileptic foci. METHODS: Cortical
      areas with decreased(11)C-flumazenil (FMZ) binding were objectively identified on
      positron emission tomography (PET) images and correlated to intracranial
      electroencephalography (EEG) findings, clinical seizure variables, histology
      findings, and surgical outcome in 20 patients (mean age, 9.9 years) with
      intractable partial epilepsy of neocortical origin and nonlocalizing magnetic
      resonance imaging (MRI). RESULTS: Focal decrease of cortical FMZ binding was
      detected in the lobe of seizure onset in 17 (85%) patients. Eleven patients (55%)
      had 17 remote cortical areas with decreased FMZ binding outside the lobe of
      seizure onset. Thirteen of those 16 (81%) of the 17 remote cortical regions that
      were covered by subdural EEG were around cortex showing rapid seizure spread on
      intracranial EEG. Remote FMZ PET abnormalities were associated with high seizure
      frequency and, when resected, showed gliosis in all six cases where material was
      available. Higher number of unresected cortical regions with decreased FMZ
      binding was associated with poorer surgical outcome. CONCLUSIONS: Focal decreases
      of cortical GABA(A) receptor binding on PET may include cortical regions remote
      from the primary focus, particularly in patients with high seizure frequency, and
      these regions are commonly involved in rapid seizure propagation. Although these
      regions may not always need to be resected to achieve seizure freedom, a careful
      evaluation of cortex with decreased GABA(A) receptor binding prior to resection
      using intracranial EEG may facilitate optimal surgical outcome in patients with
      intractable neocortical epilepsy.

PMID- 18637830
TI  - Anticonvulsant hypersensitivity syndrome: is there a role for immunomodulation?
AB  - The anticonvulsant hypersensitivity syndrome (AHS) is an idiosyncratic
      immunologic reaction to certain anticonvulsant medications, in which internal
      organ involvement may lead to fatal multisystemic failure. This syndrome has been
      associated with the use of aromatic ring-containing agents such as phenytoin,
      carbamazepine, or phenobarbitone. Clinically, this condition presents with the
      classic triad of fever, rash, and lymphadenopathy. We review the existing
      literature on AHS pathogenesis and illustrate a case complicated by liver
      dysfunction where the use of N-acetylcysteine (N-AC) and intravenous
      immunoglobulin (IVIG) may have altered the course of the disease. The rationale
      of suggesting N-AC and IVIG for the treatment of this syndrome relies on the
      theoretical synergistic effects of the two agents. Although treatment for this
      syndrome remains controversial and relies heavily on anecdotal evidence, the
      progression of hepatic injury may be prevented by the addition of N-AC. The
      scavenging properties of N-AC may palliate and possibly prevent free radical
      mediated liver damage. In addition, IVIG may effectively modulate the
      overreactive immune system in AHS. We discuss the possible role of using
      immunomodulating agents for the treatment of this syndrome and suggest that
      alternative regimens should be given special consideration especially in those
      critical clinical situations where supportive measures appear to be unsuccessful.

PMID- 18637831
TI  - Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with
      HLA-B*1502 allele in Thai population.
AB  - PURPOSE: Previous studies found a strong association between HLA-B*1502 and
      carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) in Han Chinese, but
      not in Caucasian populations. Even in Han Chinese, the HLA-B*1502 was not
      associated with CBZ-induced maculopapular eruptions (MPE). This study seeks to
      identify whether HLA-B*1502 is associated with CBZ- or phenytoin (PHT)-induced
      SJS or MPE in a Thai population. METHODS: Eighty-one Thai epileptic patients
      between 1994 and 2007 from the Chulalongkorn Comprehensive Epilepsy Program were
      recruited. Thirty-one subjects had antiepileptic drug (AED)-induced SJS or MPE (6
      CBZ-SJS, 4 PHT-SJS, 9 CBZ-MPE, 12 PHT-MPE), and 50 were AED-tolerant controls.
      RESULTS: For the first time, a strong association between HLA-B*1502 and PHT
      induced SJS was found (p = 0.005). A strong association was also found between
      the HLA-B*1502 and CBZ-induced SJS (p = 0.0005), making Thai the first non
      Chinese population demonstrating such an association. Some patients, who were HLA
      B*1502 and suffered from CBZ-induced SJS, could be tolerant to PHT and vice
      versa. This suggests that HLA-B*1502 may be a common attribute required for a
      Thai patient to develop SJS from these two AEDs; other different elements,
      however, are also needed for each AED. In addition, no association between HLA-B
      alleles and CBZ- or PHT-induced MPE was found. CONCLUSIONS: CBZ- and PHT-induced
      SJS, but not MPE, is associated with HLA-B*1502 allele in Thai population.

PMID- 18637832
TI  - Nodular heterotopia: a neuropathological study of 24 patients undergoing surgery
      for drug-resistant epilepsy.
AB  - PURPOSE: Despite the availability of detailed electroclinical and imaging data,
      only a few neuropathological studies of nodular heterotopia have been published.
      The aim of this study was to describe the neuropathological features of various
      types of nodular heterotopia obtained from patients undergoing surgery for
      intractable epilepsy. METHODS: Specimens of heterotopic nodules taken from 24
      patients were neuropathologically investigated using routine and
      immunocytochemical procedures, and the data were compared with magnetic resonance
      imaging (MRI), electroclinical findings, and surgical outcomes. RESULTS: The
      neuropathological data distinguished two groups. Group 1 (14 patients, 78% in
      Engel class 1) had similar characteristics regardless of the size, number, or
      location of the nodules, with both projecting and local circuit neurons in the
      nodules intermingled with glial cells. Thirteen patients had focal cortical
      dysplasia. The nodules were identified by MRI in all cases. In group 2 (10
      patients, 90% in Engel class 1), all of the nodules were within the temporal lobe
      and associated with hippocampal sclerosis or gangliogliomas. They were very small
      (undetected by MRI) and mainly formed by projecting neurons with no evidence of
      glial cells. All of the patients had cortical dysplasia. DISCUSSION: The
      distinctive neuropathological features of the nodules in the two groups suggest
      different etiopathogenetic mechanisms. In group 2, the presence of nodular
      formations in association with cortical dysplasia and either hippocampal
      sclerosis or ganglioglioma raises a question concerning so-called dual pathology
      in the temporal lobe.

PMID- 18637834
TI  - Lifetime fitness in two generations of Ipomopsis hybrids.
AB  - Various models purporting to explain natural hybrid zones make different
      assumptions about the fitness of hybrids. One class of models assumes that
      hybrids have intrinsically low fitness due to genetic incompatibilities, whereas
      other models allow hybrid fitness to vary across natural environments. We used
      the intrinsic rate of increase to assess lifetime fitness of hybrids between two
      species of montane plants Ipomopsis aggregata and Ipomopsis tenuituba planted as
      seed into multiple field environments. Because fitness is predicted to depend
      upon genetic composition of the hybrids, we included F1 hybrids, F2 hybrids, and
      backcrosses in our field tests. The F2 hybrids had female fitness as high, or
      higher, than expected under an additive model of fitness. These results run
      counter to any model of hybrid zone dynamics that relies solely on intrinsic
      nuclear genetic incompatibilities. Instead, we found that selection was
      environmentally dependent. In this hybrid zone, cytoplasmic effects and genotype
      by-environment interactions appear more important in lowering hybrid fitness than
      do intrinsic genomic incompatibilities between nuclear genes.

PMID- 18637833
TI  - Role of hippocampal sodium channel Nav1.6 in kindling epileptogenesis.
AB  - PURPOSE: Central nervous system plasticity is essential for normal function, but
      can also reinforce abnormal network behavior, leading to epilepsy and other
      disorders. The role of altered ion channel expression in abnormal plasticity has
      not been thoroughly investigated. Nav1.6 is the most abundantly expressed sodium
      channel in the nervous system. Because of its distribution in the cell body and
      axon initial segment, Nav1.6 is crucial for action potential generation. The goal
      of the present study was to investigate the possible role of changes in Nav1.6
      expression in abnormal, activity-dependent plasticity of hippocampal circuits.
      METHODS: We studied kindling, a form of abnormal activity-dependent facilitation.
      We investigated: (1) sodium channel protein expression by immunocytochemistry and
      sodium channel messenger RNA (mRNA) by in situ hybridization, (2) sodium current
      by patch clamp recordings, and (3) rate of kindling by analysis of seizure
      behavior. The initiation, development, and expression of kindling in wild-type
      mice were compared to Nav1.6 +/-med(tg) mice, which have reduced expression of
      Nav1.6. RESULTS: We found that kindling was associated with increased expression
      of Nav1.6 protein and mRNA, which occurred selectively in hippocampal CA3
      neurons. Hippocampal CA3 neurons also showed increased persistent sodium current
      in kindled animals compared to sham-kindled controls. Conversely, Nav1.6 +/
      med(tg) mice resisted the initiation and development of kindling. DISCUSSION:
      These findings suggest an important mechanism for enhanced excitability, in which
      Nav1.6 may participate in a self-reinforcing cycle of activity-dependent
      facilitation in the hippocampus. This mechanism could contribute to both normal
      hippocampal function and to epilepsy and other common nervous system disorders.

PMID- 18637835
TI  - Matching habitat choice causes directed gene flow: a neglected dimension in
      evolution and ecology.
AB  - Gene flow among populations is typically thought to be antagonistic to population
      differentiation and local adaptation. However, this assumes that dispersing
      individuals disperse randomly with respect to their ability to use the
      environment. Yet dispersing individuals often sample and compare environments and
      settle in those environments that best match their phenotype, causing directed
      gene flow, which can in fact promote population differentiation and adaptation.
      We refer to this process as "matching habitat choice." Although this process has
      been acknowledged by several researchers, no synthesis or perspective on its
      potentially widespread importance exists. Here we synthesize empirical and
      theoretical studies, and offer a new perspective that matching habitat choice can
      have significant effects on important and controversial topics. We discuss the
      potential implications of matching habitat choice for the degree and rate of
      local adaptation, the evolution of niche width, adaptive peak shifts, speciation
      in the presence of gene flow, and on our view and interpretation of measures of
      natural selection. Because of its potential importance for such a wide range of
      topics, we call for heightened empirical and theoretical attention for this
      neglected dimension in evolutionary and ecological studies.

PMID- 18637836
TI  - On quantifying tolerance of herbivory for comparative analyses.
AB  - As the evolutionary importance of plant tolerance of herbivory is increasingly
      appreciated, more and more studies are not just measuring a plant's tolerance,
      but are comparing tolerance among plant genotypes, populations, species, and
      environments. Here, we suggest that caution must be taken in such comparative
      studies in the choice of measurement scales (and data transformations) for damage
      levels and plant performance. We demonstrate with a simple scenario of two plant
      groups of equal tolerance how the choice of scales can lead one to infer that the
      first group is more tolerant, the second group is more tolerant, or the two
      groups are equally tolerant-using the identical dataset. We conclude that to make
      reliable, logically consistent inferences when comparing tolerances among groups
      of plants, damage and performance should both be on an additive scale or both on
      a multiplicative scale.

PMID- 18637837
TI  - Ecological reproductive isolation of coast and inland races of Mimulus guttatus.
AB  - Adaptive divergence due to habitat differences is thought to play a major role in
      formation of new species. However it is rarely clear the extent to which
      individual reproductive isolating barriers related to habitat differentiation
      contribute to total isolation. Furthermore, it is often difficult to determine
      the specific environmental variables that drive the evolution of those ecological
      barriers, and the geographic scale at which habitat-mediated speciation occurs.
      Here, we address these questions through an analysis of the population structure
      and reproductive isolation between coastal perennial and inland annual forms of
      the yellow monkeyflower, Mimulus guttatus. We found substantial morphological and
      molecular genetic divergence among populations derived from coast and inland
      habitats. Reciprocal transplant experiments revealed nearly complete reproductive
      isolation between coast and inland populations mediated by selection against
      immigrants and flowering time differences, but not postzygotic isolation. Our
      results suggest that selection against immigrants is a function of adaptations to
      seasonal drought in inland habitat and to year round soil moisture and salt spray
      in coastal habitat. We conclude that the coast and inland populations
      collectively comprise distinct ecological races. Overall, this study suggests
      that adaptations to widespread habitats can lead to the formation of
      reproductively isolated species.

PMID- 18637838
TI  - Take-off flight performance in the butterfly Pararge aegeria relative to sex and
      morphology: a quantitative genetic assessment.
AB  - Adult fitness components may strongly depend on variation in locomotory
      performance such as flight; this variation can be sex specific. Fast take-off to
      intercept females and competing males is an essential behavioral component of the
      territorial perching behavior in male speckled wood butterflies (Pararge aegeria
      L.). Females on the other hand avoid frequent take-offs particularly under
      suboptimal temperatures, typically showing fewer but longer flights than males.
      We estimated the heritability of take-off acceleration performance under
      suboptimal body temperatures by a restricted maximum-likelihood model. We
      calculated genetic correlations between this performance and a selection of
      morphological traits: size (body mass), flight muscle investment (relative thorax
      mass), and wing shape (forewing aspect ratio). Our results show significant
      additive genetic variation for mean acceleration performance and a similar but
      nonsignificant trend (P= 0.08) for maximal acceleration performance during take
      off in males (h(2)= 0.15). In females, heritability was not significantly
      different from zero for either of the acceleration performance measures.
      Morphological traits and take-off performance were genetically linked in a sex
      specific way. In males, relative thorax mass and forewing aspect ratio were
      positively genetically correlated with acceleration performance. In females,
      there was a negative genetic correlation between acceleration performance and
      abdomen mass, but not with residual abdomen mass (i.e., regressed on total body
      mass). To fully understand the evolution of sexual differences in flight
      performances and morphology, several other flight performances will have to be
      included. This multifunctional nature of flight and its consequences for the
      evolutionary study of flight has not yet been fully appreciated in the
      literature.

PMID- 18637839
TI  - Candida ratchasimensis sp. nov. and Candida khaoyaiensis sp. nov., two anamorphic
      yeast species isolated from flowers in Thailand.
AB  - Two yeast strains of the genus Candida were isolated from wild flowers collected
      in Khao Yai National Park, Nakhonratchasima Province, Thailand. Based on
      morphological, physiological and chemotaxonomic characteristics and sequence
      analysis of the D1/D2 domain of the 26S rRNA gene, strains BCC 7722(T) (=NBRC
      102563(T)=CBS 10611(T)) and BCC 7729(T) (=NBRC 102565(T)=CBS 10839(T)) were found
      to represent two distinct novel Candida species, for which the names Candida
      ratchasimensis sp. nov. and Candida khaoyaiensis sp. nov. are proposed,
      respectively. In the phylogenetic tree constructed according to the neighbour
      joining method based on sequences of the D1/D2 domain of the 26S rRNA gene,
      strains BCC 7722(T) (GenBank accession no. AY228492) and BCC 7729(T) (accession
      no. DQ400367) constituted a cluster with Candida cellae that was connected with a
      clade with Starmerella meliponinorum and Candida etschellsii. Within the D1/D2
      domain, C. ratchasimensis and C. khaoyaiensis differ from C. cellae in 25
      nucleotide substitutions with five gaps and 29 nucleotide substitutions with one
      gap, respectively.

PMID- 18637840
TI  - Loss of Zhf and the tightly regulated zinc-uptake system SpZrt1 in
      Schizosaccharomyces pombe reveals the delicacy of cellular zinc balance.
AB  - Abstract Zinc is an essential micronutrient, and yet it can be toxic when present
      in excess. Zinc acquisition and distribution are dependent on tightly controlled
      transport of Zn(2+) ions. Schizosaccharomyces pombe represents a second
      eukaryotic model to study cellular metal homeostasis. In several ways its
      micronutrient metabolism is fundamentally different from Saccharomyces
      cerevisiae. We identified the first Zn(2+)-uptake system in S. pombe and named it
      SpZrt1. Knock-out strains for all three ZIP (Zrt, Irt-like protein) transporters
      in fission yeast were constructed. Only zrt1Delta cells were unable to grow at
      low Zn(2+) and showed reduced (65)Zn(2+) uptake. Elemental profiles revealed a
      strong decrease in zinc accumulation. Cd(2+) ions inhibited uptake but Fe(2+) or
      Mn(2+) did not. Both mRNA abundance and protein amount are tightly regulated.
      Zrt1 activity is rapidly shut down upon transfer of zinc-deficient cells to zinc
      replete conditions. In cells lacking Zhf, a transporter mediating endoplasmic
      reticulum storage of zinc, this response is about 100-fold more sensitive. Thus,
      removal of excess of zinc from the cytosol is largely Zhf dependent. Moreover,
      cells deficient for both transporters are no longer able to adjust to changing
      external Zn(2+) concentrations. Optimal growth is restricted to a narrow range of
      Zn(2+) concentrations, illustrating the fine balance between micronutrient
      deficiency and toxicity.

PMID- 18637841
TI  - Identification and characterization of CaApe2--a neutral arginine/alanine/leucine
      specific metallo-aminopeptidase from Candida albicans.
AB  - The proteolytic potential of the pathogenic fungus Candida albicans was evaluated
      by the identification and functional characterization of a peptidolytic enzyme
      isolated from the cell wall of the microorganism. Determination of basic
      structural and kinetic data identified a neutral arginine/alanine/leucine
      specific metallo-aminopeptidase of unknown function termed CaApe2, which is
      encoded by ORF CaO19.5197 (GenBank RefSeq XM_705313). Mass spectrometric tryptic
      peptide analysis and N-terminal protein sequencing revealed serine-88 to
      represent the N-terminus of CaApe2. Taking into account the results of DNA and
      protein sequence analysis including inspection of the genomic region upstream of
      ORF CaO19.5197, the gene CaAPE2 is likely to consist of two exons linked by a
      phase-2 intron with exons 1 and 2 encoding a signal peptide and the amino acids
      88-954 of ORF CaO19.5197, respectively. The isolated CaApe2 protein shares an
      equally high similarity with the gene products ScAap1 and ScApe2, suggesting
      duplication of a phylogenetically ancient precursor gene in Saccharomyces
      cerevisiae. The observed failure to cleave human type-I and type-IV collagen in
      vitro challenges a direct role that secreted CaApe2 might play in the degradation
      of extracellular matrix components during host colonization, but does not exclude
      per se a contribution of the aminopeptidase to the pathogenicity of C. albicans.

PMID- 18637842
TI  - Ankle surgery in haemophilia with special emphasis on arthroscopic debridement.
AB  - Various conservative options are available to treat ankle problems in
      haemophilia, which achieve a high rate of satisfactory results in the majority of
      cases. They are usually employed in combination and include the use of patellar
      tendon bearing (PTB) orthoses and radiosynoviorthesis. The effect of the PTB
      orthoses is that it allows the patient to walk without weight bearing of the
      ankle. Radiosynoviorthesis can be performed in cases of haemophilic arthropathy
      of the ankle, provided there is at least a minimal degree of synovitis within the
      joint, with a 75% of satisfactory results. If the conservative options fail,
      surgical intervention can be indicated. Alternatives to total ankle arthroplasty
      or arthrodesis include arthroscopic debridement, removal of osteophytes of the
      anterior aspect of the distal tibia and peri-articular osteotomies to correct
      angular, rotational or translational malalignment. Ankle arthrodesis is the
      standard technique for end-stage ankle arthropathy. Arthroscopic debridement of
      the ankle with haemophilic arthropathy can offer temporary relief; however, it is
      important to stress to patients that the degree of improvement is limited. The
      complication rate in ankle arthroscopy is high compared with other joints, which
      is especially true for neurological complications and postoperative infections.
      Orthopaedic procedures are not very frequent in the haemophilic ankle, because
      the majority of problems can be solved satisfactorily by conservative means
      (radiosynoviorthesis and PTB orthosis).

PMID- 18637843
TI  - Successful management of a distal haemophilia pseudotumour: case illustration and
      literature review.

PMID- 18637844
TI  - The use of prophylaxis in 2663 children and adults with haemophilia: results of
      the 2006 Canadian national haemophilia prophylaxis survey.
AB  - Prophylaxis is standard of care for boys with severe haemophilia A. Indications
      for prophylaxis in adulthood, non-severe haemophilia A, haemophilia B and
      haemophilia with inhibitors are less well defined. This survey, conducted in
      2006, aimed to describe prophylaxis use in patients of all ages and severities
      with haemophilia A or haemophilia B in Canada. Data on 2663 individuals (2161
      haemophilia A; 502 haemophilia B), including 78 inhibitor-positive patients, were
      returned by 22/25 Canadian haemophilia treatment centres. This represented 98% of
      the Canadian haemophilia population. Frequency of prophylaxis use, defined as
      infusion of factor VIII/IX concentrate at least once weekly for >/=45 weeks of
      the year, was highest in individuals with severe haemophilia A (69%). It was
      lower in individuals with severe haemophilia B (32%), moderate haemophilia A
      (18%) or B (5%) and mild haemophilia A (1%) or B (1%). Among individuals with
      severe haemophilia A, the frequency of prophylaxis use was 84% in children (</=18
      years) and 55% in adults (>18 years). Thirteen per cent of inhibitor-positive
      individuals were receiving prophylaxis with bypassing agents. Comparison with
      data obtained from a 2002 Canadian survey showed a greater use of prophylaxis in
      children </=5 years of age with severe haemophilia A (73% vs. 49%). Prophylaxis
      is no longer confined to children with severe haemophilia A, but is used in a
      significant proportion of adults with severe haemophilia A and individuals with
      severe haemophilia B or moderate haemophilia A. Prophylaxis is being started
      earlier in boys with severe haemophilia A.

PMID- 18637845
TI  - Intracranial haemorrhage in patients with congenital haemostatic defects.
AB  - We investigated 52 of 457 patients with congenital factor deficiencies with 57
      episodes of intracranial haemorrhage (ICH) between 1998 and 2007. There were 38
      severe haemophiliacs, 6 with factor XIII deficiency, 5 with factor X deficiency,
      2 factor V-deficient patients, and 1 with type 3 von Willebrand disease (VWD).
      The median age was 8 years (range 1 month-22 years). Most patients were below 15
      years of age (86.5%). All patients with factor X deficiency were between 1 and 5
      months of age. ICH was the primary bleeding episode leading to detection of
      factor deficiency in 19.2% (five patients with severe haemophilia and all
      patients with factor X deficiency). Trauma caused bleeding in 66%. None of the
      patients with factor X deficiency had history of prior trauma. Surgery was
      performed in five patients with subdural haematomas, all of whom survived.
      Conservative factor replacement with 100% correction for 3 days followed by 50
      60% correction for 7 days was possible in 60% patients. Seizures requiring
      prolonged therapy were noted in eight patients. Death was recorded in 15 patients
      (29%). Inadequate therapy in the form of delay or insufficient replacement was
      noted in 7/15 deaths. ICH was seen in 11.3% of all patients with coagulation
      factor deficiencies. Factor X deficiency presented with ICH at an earlier age.
      Inadequate replacement therapy including delayed treatment caused nearly 50% of
      all deaths. Most patients can be managed satisfactorily with adequate replacement
      therapy alone, with surgery being reserved for those with worsening neurological
      conditions.

PMID- 18637846
TI  - The molecular analysis of von Willebrand disease: a guideline from the UK
      Haemophilia Centre Doctors' Organisation Haemophilia Genetics Laboratory Network.
AB  - von Willebrand disease (VWD) is a common autosomally inherited bleeding disorder
      associated with mucosal or trauma-related bleeding in affected individuals. VWD
      results from a quantitative or qualitative deficiency of von Willebrand factor
      (VWF), a glycoprotein that is essential for primary haemostasis and that carries
      and protects coagulation factor VIII (FVIII) in the circulation. Through
      characterization of the phenotype and identification of mutations in the VWF gene
      in patients with VWD, understanding of the genetics and biochemistry of VWF and
      VWD has advanced considerably. The importance of specific regions of VWF for its
      interaction with other components of the vasculature has been revealed, and this
      has facilitated the formal classification of VWD into three subtypes based upon
      quantitative (types 1 and 3) and qualitative (type 2) deficiency of VWF. The
      underlying genetic lesions and associated molecular pathology have been
      identified in many cases of the qualitative type 2 VWD variants (2A, 2B, 2M, 2N)
      and in the severe quantitative deficiency, type 3 VWD. However in the partial
      quantitative deficiency, type 1 VWD, the picture is less clear: there is a
      variable relationship between plasma levels of VWF and bleeding, there is
      incomplete penetrance and variable expressivity within affected families, the
      causative molecular defect is unknown in a substantial number of cases, and even
      in those cases where the causative mutation is known, the associated molecular
      pathology is not necessarily understood. This guideline aims to provide a
      framework for best laboratory practice for the genetic diagnosis of VWD, based
      upon current knowledge and understanding.

PMID- 18637847
TI  - Differences in the confluence of mesial canals in mandibular molar teeth with
      three or four root canals.
AB  - AIM: To investigate the correlation between number of root canals and their
      confluence in mandibular molar teeth. METHODOLOGY: A total of 553 first and 383
      second mandibular molars were root filled between the beginning of 1997 and the
      end of 2006. Access cavities were prepared and the pulp chamber floors were
      carefully inspected with an endodontic explorer under magnification of 4x. After
      negotiating the root canal system, the 'straightest' canal of each root was
      instrumented. A gutta-percha cone was placed in the canal and a small file (08 or
      10) was inserted to working length and then removed in all other canals. The
      gutta-percha cone was removed and inspected for notches indicating the presence
      of confluences. If it was not possible to probe completely one or more canals,
      the canal confluences were classified as 'not determined' (ND) if there was no
      sign of confluence; if a notch was present canals were considered confluent. For
      each tooth, the number of root canals and the presence of confluences were
      recorded. To test whether there was a difference in frequency of confluences
      between teeth with three and four root canals the chi-squared analysis with
      Yates' continuity correction was performed. RESULTS: The frequency of a
      confluence in mesial canals of first molars was 56% in teeth with three root
      canals and 34% in teeth with four canals. In second molars, it was 67 and 41%,
      respectively. Differences in the frequency of confluences in teeth with three and
      four root canals were statistically significant both in first and in second
      molars. CONCLUSIONS: A greater incidence of confluent canals occurred in teeth
      with three rather than with four root canals both in first and second mandibular
      molars.

PMID- 18637848
TI  - Immunohistochemical localization of oncostatin M in epithelialized apical
      periodontitis lesions.
AB  - AIM: To investigate the in situ location of oncostatin M (OSM) in epithelialized
      apical periodontitis lesions. METHODOLOGY: Thirty periapical lesions of pulpal
      origin were collected with informed consent from patients at the time of apical
      surgery. Tissue specimens were fixed with 10% buffered formalin overnight,
      dehydrated in an ascending series of graded alcohol, and embedded in paraffin.
      Five micron sections from formalin-fixed, paraffin-embedded specimens were
      examined by immunohistochemistry. In addition, another section from each specimen
      was stained with haematoxylin and eosin to assess the presence of inflammatory
      infiltrates. Differences in OSM expression between tissue with low and high
      levels of inflammation were subsequently analyzed by Fisher's exact test.
      RESULTS: Based on histological examination of haematoxylin and eosin stained
      sections, all specimens revealed the morphology of epithelialized apical
      periodontitis lesions. The results from immunohistochemistry demonstrated that
      OSM stain was detected in the inflammatory infiltrates, epithelium, connective
      tissue, and endothelium. The OSM signal was mainly expressed in endothelial cells
      (100%) followed by inflammatory cells (93.33%), epithelial cells (53.33%), and
      fibroblasts (16.67%). In addition, OSM expression was significantly higher in
      epithelialized apical periodontitis with higher levels of inflammatory
      infiltrates (P < 0.001). CONCLUSIONS: Oncostatin M was found to be expressed in
      epithelialized apical periodontitis lesions and would form part of the cytokine
      network involved in the disease process of apical periodontitis.

PMID- 18637849
TI  - Phosphatidylinositol-3-kinase inhibitor LY 294002 blocks Streptococcus mutans
      induced interleukin (IL)-6 and IL-8 gene expression in odontoblast-like cells.
AB  - AIM: To investigate the involvement of the phosphatidylinositol-3-kinase (PI3K)
      in interleukin-6 (IL-6) and interleukin-8 (IL-8) gene expression in odontoblast
      like cells when exposed to heat-killed Streptococcus mutans. METHODOLOGY:
      Cultured human odontoblast-like cells (Dulbecco's modified Eagle's medium) were
      pre-treated with a specific inhibitor for PI3K (LY 294002) and subsequently
      stimulated with heat-killed S. mutans for 6 and 24 h. After stimulation, RNA was
      extracted from the cells and cDNA synthesis was performed. Gene expression of IL
      6 and IL-8 was analysed by real-time polymerase chain reaction and normalized to
      the gene expression of beta-actin. Cell survival was determined for stimulation
      experiments. RESULTS: The gene expression of IL-6 and IL-8 was significantly
      increased in response to heat-killed S. mutans (P = 0.002 and P < 0.001,
      respectively). After 6 h, the mRNA expression of IL-6 and IL-8 was significantly
      higher than after 24 h of stimulation (P = 0.019 and P < 0.001, respectively).
      Pre-treatment with the inhibitor LY 294002 blocked the induced gene expression of
      IL-6 and IL-8 (P = 0.002 and P < 0.001, respectively). No differences in viable
      cell counts were found after stimulation with heat-killed S. mutans and/or pre
      treatment with LY 294002 compared with the unstimulated control. CONCLUSION: Gene
      expression of IL-6 and IL-8 was induced by heat-killed S. mutans via signalling
      pathways mediated by PI3K. These findings indicate that odontoblasts respond to
      cariogenic bacteria with increased gene expression of pro-inflammatory mediators
      and hence participate in immune processes.

PMID- 18637850
TI  - Root and canal morphology of the mesiobuccal and distal roots of permanent first
      molars in a Kuwait population--a clinical study.
AB  - AIM: To identify the number of roots and canal configurations in permanent first
      molars of the indigenous Kuwaiti sub-population and compare them against a
      similar group of non-Kuwaiti population in different age groups and gender, and
      to determine the frequency of a second canal in the mesiobuccal root of maxillary
      first molars and distal root of mandibular first molars that could be located and
      treated in routine practice without using magnification or special lighting
      conditions. METHODOLOGY: A total of 220 permanent first molar teeth of patients
      scheduled for root canal treatment over a period of 1 year were included.
      Patients were identified and grouped according to their nationality as Kuwaiti
      and non-Kuwaiti (which included Filipinos, Indonesian Indians, Srilankans,
      Egyptians, Saudi Arabians and Syrians). In both nationality groups, patients were
      successively distributed into four groups based on their age. The first age group
      included patients below 20 years, the second 21-30 years, the third 31-40 years
      and the fourth were over 40 years. The first three groups comprised of 15 male
      and 15 female patients whilst the fourth group had 10 patients of each gender.
      Teeth with open apices, resorptions and calcification were excluded from the
      study. The teeth included were both clinically and radiographically examined for
      number of roots, the canal configuration and the presence of the additional
      mesiobuccal and distal canals and recorded. The simplified classification of
      canal configurations proposed by Weine was utilized. RESULTS: The incidence of a
      second canal in the mesiobuccal (MB) root of maxillary first molars and the
      distal root of mandibular first molars was not influenced significantly by
      nationality and gender. All the 110 maxillary first molars treated had three
      roots; 58% of MB root had one canal and 42% had two canals. The majority of the
      mesial roots had Weine type II canal configuration when the second mesiobuccal
      canal was present. All distobuccal and palatal roots had a single or type I canal
      configuration. Of the 110 mandibular first molars that were treated, 96% had two
      roots and 4% had three roots. When present, the third root was located either
      buccal or lingual to the main distal root. Overall 51% of the single distal roots
      had one canal whilst 49% had two canals. The mesial root frequently had a Weine
      type II canal configuration as did the distal root when a second canal was
      present. Pearson's correlation analysis of both molars revealed a significant (P
      < 0.05) negative correlation (r = -0.274, r = -0.144) between age and number of
      canals as well as the type of canal. CONCLUSIONS: The incidence of a second canal
      in distal roots of permanent mandibular first molars was 49% in the Kuwaiti
      population and this was similar to other Asian ethnic populations. Adopting
      modified access and troughing procedures revealed a 42% frequency of MB2 canals
      in maxillary first molars. The incidence of a second canal in both mesiobuccal
      roots of maxillary molars and distal roots of mandibular molars decreased
      significantly with age; no differences were noticed amongst the nationalities and
      gender studied. The possibility of extra roots should be anticipated in
      mandibular molars.

PMID- 18637851
TI  - In-depth hardness profiles of stainless steel and Ni-Ti endodontic instrument
      cross-sections by nano-indentation.
AB  - AIM: To evaluate the in-depth hardness profiles of Stainless Steel (SS) and
      nickel titanium (Ni-Ti) endodontic instrument cross-sections using a nano
      indentation technique. METHODOLOGY: Three SS (Reamer, K and Hedstrom) and three
      Ni-Ti (ProFile, NRT and Liberator) instruments were studied. After embedding and
      metallographic preparation the in-depth hardness profiles of instrument cross
      sections were measured starting from the cutting surface towards the centre to a
      depth of 2000 nm using an MTS XP nanoindenter with a Berkovich diamond indenter.
      The results of hardness measurements of outer (near to cutting edge) and inner
      locations were statistically analyzed by two-way anova followed by SNK test
      (alpha = 0.05). RESULTS: For all instrument cross-sections the maximum hardness
      was obtained at the outer surface followed by hardness attenuation towards the
      centre of the cross section. The statistical analysis of hardness classified the
      instruments, for both outer and innermost locations, to the following decreasing
      order: Reamer > K > Hedstrom > Profile > NRT shank (without thermal treatment) >
      NRT tip (with thermal treatment) > Liberator. The maximal hardness, at the outer
      surface of endodontic instruments, can be attributed to the residual stresses
      developed due to cutting and thermal effects during the manufacturing process.
      The increased outer layer hardness may have a beneficial effect on the cutting
      ability and wear resistance of endodontic instruments. CONCLUSIONS: All
      endodontic instruments had a decrease in hardness towards their centre. This
      implies that the surface hardness of contemporary endodontic instruments is
      significantly enhanced by the consequences of manufacturing processes.

PMID- 18637852
TI  - Accuracy of two root canal length measurement devices integrated into rotary
      endodontic motors when removing gutta-percha from root-filled teeth.
AB  - AIM: To evaluate ex vivo the accuracy of the integrated electronic root canal
      length measurement devices within TCM Endo V and Tri Auto ZX motors whilst
      removing gutta-percha and sealer from filled root canals. METHODOLOGY: Forty
      freshly extracted maxillary and mandibular incisor teeth with mature apices were
      selected. Following access cavity preparation, the length of the root canals were
      measured visually 0.5 mm short of the major foramen (TL). The canals were
      prepared using the HERO 642 system and then filled with gutta-percha and AH26
      sealer using a lateral compaction technique. After 7 days the coronal temporary
      filling was removed and the roots mounted in an alginate experimental model. The
      roots were then randomly divided in two groups. The access cavities were filled
      with chloroform to soften the gutta-percha and allow its penetration using the
      Tri Auto ZX and the TCM Endo V devices in groups 1 and 2, respectively. The
      'automatic apical reverse function' (ARL) of both devices was set to start at the
      0.5 setting and the rotary instrument inserted inside the root canal until a
      beeping sound was heard and the rotation of the file stopped automatically. Once
      the auto reverse function had been initiated, the foot pedal of the motor was
      inactivated and the rubber stop placed against the reference point. The distance
      between the file tip and rubber stop was measured using a digital calliper to
      0.01 mm accuracy (ARL). Then, a size 20, 0.02 taper instrument was attached to
      each device and inserted into the root canals without rotary motion until the
      integrated ERCLMDs positioned the instrument tips at the 0.5 setting as suggested
      by the devices. This length was again measured using a digital calliper (EL). The
      Mann-Whitney U-test was used to investigate statistical differences between the
      true canal length and those indicated by the two devices when used in 'automatic
      ARL and when inserted passively (EL). RESULTS: In the presence of gutta-percha,
      sealer and chloroform, the auto-reverse function for the Tri Auto ZX and TCM Endo
      V, set to start at 0.5 level, was initiated beyond the foramen in 60% and 95% of
      the samples, respectively during active (rotary) penetration of the instruments.
      There was a statistically significant difference between the devices for the mean
      discrepancies between the length at which the auto reverse function was initiated
      and the true length (P < 0.001). Electronic detection of the apical terminus when
      the instruments were introduced passively (not rotating) was beyond the foramen
      in 20% and 37% of cases in the Tri Auto ZX group and the TCM Endo V group,
      respectively. There was a statistically significant difference between the
      devices for the mean discrepancies between the electronically determined
      (passive) length and true length (P < 0.01). CONCLUSION: The auto reverse
      function of the Tri Auto ZX and TCM Endo V devices, set to start at 0.5 level,
      were initiated beyond the foramen in the majority of root-filled teeth during
      active (rotating) penetration of root filling material. Thus, this automatic
      function must be used with caution when removing gutta-percha root fillings.
      There were significant differences between the accuracy of measurements in active
      (rotating) and passive (not-rotating) modes; both devices were more accurate when
      used in passive mode. However, the Tri Auto ZX was significantly more accurate in
      a greater proportion of cases.

PMID- 18637853
TI  - A diagnostic dilemma: endodontic lesion or odontogenic keratocyst? A case
      presentation.
AB  - AIM: To present a clinical case of odontogenic keratocyst (OKC) simulating a
      lateral periodontal cyst. SUMMARY: A 39-year-old female complaining of swelling
      and pain in the left mandibular premolar area was found to have a radiolucent
      lesion between teeth 34 and 35 (FDI). Both teeth had incomplete root fillings,
      and orthograde re-treatment of both premolars was performed. At 2-year follow-up,
      radiographic examination showed an increase in the radiolucent defect with
      respect to the previous examination. A surgical treatment of tooth 34 was then
      performed, with histological examination of the lesion. Histological features
      were consistent with an OKC, and the lesion was successfully treated by complete
      enucleation and application of Carnoy's solution. At 2-year follow-up, no
      clinical signs or symptoms were found and the radiolucent area had disappeared.
      KEY LEARNING POINTS: Odontogenic keratocysts may mimic endodontic lesions.
      Clinicians should carefully review their cases and consider surgical intervention
      with biopsy in cases that do not heal.

PMID- 18637854
TI  - Dominant ants can control assemblage species richness in a South African savanna.
AB  - 1. Competition is considered a key factor structuring many communities, and has
      been described as the 'hallmark' of ant ecology. Dominant species are thought to
      play a key role structuring local ant assemblages through competitive exclusion.
      2. However, while there have been many studies demonstrating competitive
      exclusion and consequently reduced richness at baits, it is not clear whether
      such regulation of 'momentary' diversity at clumped food resources can scale up
      to the regulation of richness at the site or assemblage level. 3. In this study,
      ant assemblages were sampled in three different savanna habitats in South Africa
      using both baiting and pitfall trapping. 4. As has been found in previous
      studies, there was a unimodal relationship between dominant ants and species
      richness at baits, with high abundances of dominant ants regulating species
      richness through competitive exclusion. Analysis of pitfall samples revealed
      strong convergence in pattern, and results from null model co-occurrence analyses
      supported the findings. 5. The importance of competition in structuring local ant
      assemblages was, however, only apparent at one of the three savanna habitats
      suggesting that a full range of extreme environments is needed to produce the
      full unimodal relationship at the assemblage level. 6. Although the relative
      importance of competition varied with habitat type, the study demonstrated that
      in some habitats, dominant ants can control species richness at the assemblage
      level.

PMID- 18637855
TI  - Lizards combine stored energy and recently acquired nutrients flexibly to fuel
      reproduction.
AB  - 1. Energy allocation strategies for reproduction are viewed typically as a
      continuum between reliance on 'income' (recently acquired energy) vs. 'capital'
      (stored reserves) for fuelling reproduction. Because ectothermy facilitates long
      term energy storage and often involves low feeding rates, traditional views
      suggest that many ectotherms rely heavily on stored reserves for egg production.
      2. We explored the temporal relationship between energy intake and expenditure in
      a multi-clutching lizard (Amphibolurus muricatus) by evaluating the effect of
      maternal nutrition on reproductive output and by contrasting delta(13)C
      measurements of the maternal diet and endogenous energy stores with that of the
      eggs produced. 3. Our experiment revealed that females utilize both endogenous
      energy stores and recently acquired food to fuel reproduction; this pattern did
      not shift seasonally from first to second clutches produced. Importantly,
      however, egg lipid was derived primarily from capital, whereas egg protein was
      derived about equally from both income and capital. 4. Overall, these results
      suggest that the energy allocation strategy used for reproduction differs among
      egg components, and that the use of recently acquired energy for reproduction may
      be more widespread in ectotherms than thought previously.

PMID- 18637856
TI  - Critical care nurses' decision making: sedation assessment and management in
      intensive care.
AB  - AIMS: This study was designed to examine the decision making processes that
      nurses use when assessing and managing sedation for a critically ill patient,
      specifically the attributes and concepts used to determine sedation needs and the
      influence of a sedation guideline on the decision making processes. BACKGROUND:
      Sedation management forms an integral component of the care of critical care
      patients. Despite this, there is little understanding of how nurses make
      decisions regarding assessment and management of intensive care patients'
      sedation requirements. Appropriate nursing assessment and management of sedation
      therapy is essential to quality patient care. DESIGN: Observational study.
      METHODS: Nurses providing sedation management for a critically ill patient were
      observed and asked to think aloud during two separate occasions for two hours of
      care. Follow-up interviews were conducted to collect data from five expert
      critical care nurses pre- and postimplementation of a sedation guideline. Data
      from all sources were integrated, with data analysis identifying the type and
      number of attributes and concepts used to form decisions. RESULTS: Attributes and
      concepts most frequently used related to sedation and sedatives, anxiety and
      agitation, pain and comfort and neurological status. On average each participant
      raised 48 attributes related to sedation assessment and management in the
      preintervention phase and 57 attributes postintervention. These attributes
      related to assessment (pre, 58%; post, 65%), physiology (pre, 10%; post, 9%) and
      treatment (pre, 31%; post, 26%) aspects of care. CONCLUSIONS: Decision making in
      this setting is highly complex, incorporating a wide range of attributes that
      concentrate primarily on assessment aspects of care. RELEVANCE TO CLINICAL
      PRACTICE: Clinical guidelines should provide support for strategies known to
      positively influence practice. Further, the education of nurses to use such
      guidelines optimally must take into account the highly complex iterative process
      and wide range of data sources used to make decisions.

PMID- 18637857
TI  - Effect of nursing interventions on stressors of parents of premature infants in
      neonatal intensive care unit.
AB  - AIM: This study was planned for the purpose of determining the effect of stress
      reducing nursing interventions on the stress levels of mothers and fathers of
      premature infants in a Neonatal Intensive Care Unit (NICU). DESIGN: Randomised
      intervention. BACKGROUND: The physical and psychosocial environment of the NICU
      is a major factor in the stress experienced by the family. METHOD: Interviews
      were conducted with the parents of premature infants who agreed to participate in
      the research. An approximately 30-minute educational programme about their infant
      and the intensive care unit was held for the mothers and fathers in the
      intervention group within the first week after their infant was admitted to the
      intensive care unit. Then they were introduced to the unit and personnel. They
      were given the information they requested and their questions were responded to.
      The parents in the control group received nothing in addition to the routine unit
      procedures. The mothers and fathers' stress scores were measured for both groups
      after their infants' 10th day in the NICU with the Parental Stress Scale: NICU
      (PSS:NICU). RESULTS: The difference between the intervention group and the
      control group mothers' mean stress score was found to be statistically
      significant (t = 4.05, p < 0.05). It was determined that the stress scores for
      the fathers in the treatment group in this research were lower, but the
      difference between the two groups was not found to be statistically significant
      (p > 0.05). CONCLUSION: It has been determined that parents experience very high
      stress levels when their infants are admitted to an NICU and that there are
      nursing interventions which can be implemented to decrease their levels of
      stress. RELEVANCE TO CLINICAL PRACTICE: Determining the sources of stress
      experienced by parents can help NICU nurses use appropriate interventions in
      cooperation with other members of the team to decrease the stress that parents
      experience.

PMID- 18637858
TI  - Effectiveness of the PLISSIT model for solving the sexual problems of patients
      with stoma.
AB  - AIMS AND OBJECTIVES: This study was carried out to assess the effectiveness of
      the PLISSIT model in solving sexual problems of individuals with stoma.
      BACKGROUND: Creating a stoma due to intestinal cancer may prolong the life
      expectancy of individuals. However, the problems resulting from stoma may cause
      significant changes in an individual's life and adversely affect relations with
      family members and social and sexual life. DESIGN: Experimental. METHODS: The
      study consisted of individuals with stoma, living in Ankara. The sample consisted
      of 60 patients. The case group consisted of 30 patients living in Ankara; and the
      control group consisted of 30 patients living outside Ankara. In data collection,
      a questionnaire form, the PLISSIT model intervention plan and Golombok-Rust
      Inventory of Sexual Satisfaction (GRISS) were used. The individuals in the case
      group were paid eight home visits. During these visits, sexual problems of
      individuals with stoma were assessed and solutions sought under the guidance of
      the PLISSIT model intervention plan. RESULTS: Increase of mean scores of Golombok
      Rust Inventory of Sexual Satisfaction and subgroups before evaluating the sexual
      problems by the PLISSIT model and the sixth week scores which the sexual activity
      is anticipated to start have been observed, but after evaluating the sexual
      problems by using the model, the mean scores decreased. It was determined that
      negative effects of concerns related to sexual life; some physical and emotional
      features and physiological problems have been observed and difference between the
      groups is significant (p < 0.05). CONCLUSIONS: As a result, it can be claimed
      that decreasing sexual problems can be accomplished by using the PLISSIT model.
      RELEVANCE TO CLINICAL PRACTICE: People with stoma can meet sexual problems.
      However, nurses experience some difficulties while handling sexual problems. It
      is thought that an intervention plan prepared within the framework of the PLISSIT
      model will guide nurses in solving sexual problems of individuals with stoma and
      providing integrated care and help individuals to express their sexual problems.

PMID- 18637859
TI  - Decreased number of Langerhans cells in basal cell carcinoma.

PMID- 18637860
TI  - The prevalence of melanocytic naevi among schoolchildren in South Hungary.
AB  - BACKGROUND: Malignant melanoma is an increasing public health problem worldwide;
      accordingly, identification of the constitutional and environmental factors which
      contribute to the development of the disease, and hence identification of the
      individuals at high risk of melanoma, is an indispensable step in all primary
      prevention efforts. OBJECTIVES: This paper aims to assess the prevalence of
      different pigmented lesions among schoolchildren and to investigate their
      relationship with phenotypic pigmentary characteristics, sun exposure and other
      factors. PATIENTS/METHODS: A cross-sectional study was performed in two secondary
      schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years,
      underwent a whole-body skin examination. A standardized questionnaire was used to
      collect data on phenotypic, sun exposure and other variables. RESULTS: One to 10
      common melanocytic naevi were found in 27% of the participants, and the naevus
      numbers were in the range of 10-100 in 67%; 5.4% of them had more than 100 common
      melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%.
      Statistically significant associations were found between the number of pigmented
      lesions and gender, hair colour, eye colour, skin phototype, a history of severe
      painful sunburns and a family history of a large number of melanocytic naevi.
      CONCLUSION: Our study population displayed a markedly high prevalence of
      clinically atypical melanocytic naevi. Moreover, a considerable proportion of the
      investigated individuals had multiple common melanocytic naevi. Since the
      presence of a large number of melanocytic naevi is a strong predictor for future
      melanoma development, health educational programmes on melanoma prevention should
      be aimed at young age groups.

PMID- 18637861
TI  - Pigmentary mosaicism with hyperpigmented streaks on the palmoplantar lesion
      associated with balanced X; autosome translocations t(X; 9)(p11.21; q34.1).

PMID- 18637862
TI  - Pemphigus.
AB  - Pemphigus refers to a group of potentially life-threatening autoimmune diseases
      of the skin and mucous membranes, characterized by the formation of blisters and
      erosions of the skin. An autoimmune process, directed against keratinocyte
      desmosomal cadherins, interferes with the adhesive function of these molecules.
      This results in the separation of keratinocytes and clinical manifestation of
      blistering. Differences in the particular antigens targeted by the antibodies and
      in the distribution of these antigens in the different regions of the body and in
      the separate layers of the epidermis result in different clinical manifestations
      of the disease. Diagnosis of pemphigus is based on three independent groups of
      criteria: clinical features (flaccid blisters and erosions on skin and oral
      mucosa), histologic findings (epidermal acantholysis) and immunological tests
      (circulating and skin-fixed antibodies against keratinocyte surface antigens).
      The principle aim of treatment is to reduce inflammatory response and
      autoantibody production, thereby achieving disease remission.Systemic
      corticosteroids are still the most useful drugs in the treatment of pemphigus and
      continue to be the mainstay of therapy for this disease.Adjuvant drugs, such as
      immunosuppressants, are commonly used in combination, in order to increase
      efficacy and have a steroid-sparing effect,thereby allowing reduced maintenance
      doses and less side effects of systemic corticosteroids. Other options include
      intravenous immunoglobulin and plasmapheresis. However, more research is needed
      to develop treatments with the least possible toxicity.

PMID- 18637863
TI  - CD30-positive anaplastic large T-cell lymphoma of the tongue.

PMID- 18637864
TI  - Parallel occurrence of Erdheim-Chester disease and eosinophilic granuloma in the
      same patient.

PMID- 18637865
TI  - Diffuse normolipaemic plane xanthomatosis associated with adult T-cell
      lymphoma/leukaemia.

PMID- 18637866
TI  - An unusual case of child head injury by coat hanger*.
AB  - Traumatic brain injury is the leading cause of morbidity and mortality among
      children suspected of child abuse. Penetrating cranio-facial injuries are
      generally rare in the pediatric age group and are caused by both accidental and
      inflicted mechanisms. We report an unusual case of a 2-year-old female who was
      admitted to a pediatric emergency room with an industrial stainless steel coat
      hanger impaled in her skull. Pertinent clinical forensic medicine examination,
      coupled with home inspection and interviews by the local law enforcement,
      revealed a horrible episode of domestic violence.

PMID- 18637867
TI  - Claims of amnesia for criminal offenses: psychopathology, substance abuse, and
      malingering.
AB  - The forensic psychiatric examiner often encounters defendants who deny memory for
      their offense. Past research proposes a variety of factors to account for offense
      amnesia. To date there have been few systematic studies of offense amnesia in
      relation to psychiatric diagnosis, either alone or in combination with other
      known factors such as substance use and malingering. We studied 53 pretrial
      felony defendants who had been referred for psychiatric examination; 40% claimed
      amnesia for their offense. Examinees with psychotic disorders in general, and
      schizophrenia in particular, were relatively less likely to claim amnesia than
      were examinees with other diagnoses. Substance use at the time of the offense and
      associated substance use disorder diagnoses were positively associated with
      offense amnesia. Malingering diagnosed by general clinical criteria was a poor
      predictor of amnesia claims. These data suggests that two prominent reasons for
      referral for forensic psychiatric evaluation include the presence of psychotic
      symptoms and claims of amnesia for the offense.

PMID- 18637868
TI  - Age estimation from the human os coxa: a test on a documented Italian
      collection*.
AB  - Current standards for age at death estimation from the pelvis are based on
      Americans of European and African ancestry. Our limited understanding of
      population variability hampers our efforts to apply these techniques to the
      various skeletal populations around the world, especially in global forensic
      contexts. However, documented skeletal samples are rare, limiting our ability to
      test our techniques. This study tested the Suchey-Brooks pubic symphysis aging
      method and the auricular surface method originally developed by Lovejoy et al. on
      a large sample (n = 404) of known sex and age from the Sassari Collection, housed
      at the Museum of Anthropology at the University of Bologna, Italy. The results
      indicate that for both methods, bias and inaccuracy increased with age and actual
      age tended to be underestimated over the age of 40. The auricular surface method
      performed slightly better, exhibiting slightly lower levels of bias and
      inaccuracy, especially for males.

PMID- 18637869
TI  - N-cyanomethyl-N-methyl-1-(3',4'-methylenedioxyphenyl)-2-propylamine: an MDMA
      manufacturing by-product.
AB  - This paper describes the structural elucidation of a compound produced during the
      synthesis of 3,4-methylenedioxymethylamphetamine (MDMA) via the reductive
      amination of 3,4-methylenedioxyphenyl-2-propanone (3,4-MDP-2-P) with methylamine
      and sodium cyanoborohydride. The compound was isolated from MDMA by column
      chromatography, proton and carbon nuclear magnetic resonance spectroscopy,
      LC/mass spectrometry, and total synthesis were used to identify the compound as N
      cyanomethyl-N-methyl-1-(3',4'-methylenedioxyphenyl)-2-propylamine. This compound
      has been identified as a potential synthetic route marker for the reductive
      amination of 3,4-MDP-2-P with methylamine and sodium cyanoborohydride and as such
      it should prove valuable to forensic scientists engaged in profiling illicit
      drugs. Profiling MDMA can provide useful information to law enforcement agencies
      relating to synthetic route, precursor chemicals and reagents employed and may be
      used for comparative analyses of different drug seizures. This paper also
      describes the structural elucidation of the analogous methylamphetamine synthetic
      route marker compound, N-cyanomethyl-N-methyl-1-phenyl-2-propylamine, produced
      during the reductive amination of phenyl-2-propanone using methylamine and sodium
      cyanoborohydride.

PMID- 18637870
TI  - Applicability of two commercially available kits for forensic identification of
      saliva stains.
AB  - The RSID-saliva test and the SALIgAE-saliva test are two recently developed
      forensic saliva detection kits. In this study, we compared the sensitivity and
      the specificity of the two test kits with the Phadebas amylase test by analyzing
      amylases from various sources including human, animals, plants, and micro
      organism. The data demonstrate that the RSID-saliva test and the SALIgAE-saliva
      test offer higher sensitivity and specificity for the detection of saliva than
      the Phadebas amylase test. The detection limits of the RSID-saliva test, the
      SALIgAE-saliva test, and the Phadebas amylase test equate to 10, 4, and 1000 nL,
      respectively for human saliva. The RSID-saliva test and the SALIgAE-saliva test
      were further evaluated by analyzing semen, vaginal secretion, breast milk, blood,
      urine, sweat, and feces. The results of the two tests are in good agreement. The
      two tests reacted with urine, breast milk, and feces, but not with semen, vaginal
      secretion, blood, and sweat.

PMID- 18637871
TI  - How reliable is reported sleeping position in cases of unexpected infant death?
AB  - Examination of sudden infant death syndrome (SIDS) deaths in South Australia over
      a 7-year period from 2000 to 2006 was undertaken. There were 32 out of 35 cases
      where details of position when found were known. The data confirmed a marked
      decline in deaths in the prone position over the past decade, but showed no
      significant decline in cases reportedly found dead in the supine position.
      Posterior lividity was present in most cases (n = 30), 10 of whom also had
      anterior lividity. Posterior lividity was attributable either to the position of
      the body after death or to the effect of supine postmortem storage. In six cases,
      however, fixed anterior lividity indicated that death had occurred in the prone
      position despite statements that the infants had been found on the side (n = 1)
      and in the supine position (n = 5). This contradiction indicates that caregivers'
      descriptions of terminal sleeping positions may not be supported by autopsy
      findings. The numbers of SIDS deaths reported in the supine position in South
      Australia may not, therefore, represent a genuine tally, but instead may be a
      function of inaccurate reporting. This may act as a confounding factor in studies
      attempting to link sleeping position with other risk factors.

PMID- 18637872
TI  - Calliphora vicina (Diptera: Calliphoridae) collected from a human corpse above
      3400 m in elevation.
AB  - In the summer of 2005 an adult hiker was killed in a fall in Rocky Mountain
      National Park, Colorado (U.S.A.). His body was subsequently colonized by the
      blowfly Calliphora vicina (Diptera: Calliphoridae). The body was discovered 9
      days later at an elevation of 3475 m (11,400 feet). This is the first report of
      C. vicina on a human corpse at this elevation in Colorado. This paper provides
      additional confirmation of this fly colonizing a human corpse at high elevations
      in Colorado.

PMID- 18637873
TI  - Recovery efficiencies of anthrax spores and ricin from nonporous or nonabsorbent
      and porous or absorbent surfaces by a variety of sampling methods*.
AB  - The 2001 anthrax letter cases brought into focus the need to establish the most
      effective environmental sampling procedures. Results are presented from two
      studies aimed at establishing the best procedures for everyday surfaces likely to
      be contaminated after the release of environmentally stable bioaggressive agents,
      as exemplified by anthrax spores and ricin. With anthrax spores, contact plates,
      with mean retrieval rates of 28-54%, performed better than other methods by a
      wide margin for flat nonporous, nonabsorbent surfaces. They also proved best on
      flat porous, absorbent materials, although recoveries were low (<7%). For both
      agents, dry devices (swabs, wipes, Trace Evidence Collection Filters) had
      universally poor retrieval efficiencies with no significant differences between
      them. Among moistened devices (wipes, swabs, and Sample Collection and Recovery
      Devices), wipes were generally best, albeit with considerable cross-over among
      individual readings (highest mean recoveries for anthrax spores and ricin 5.5%
      and 2.5%, respectively, off plastic).

PMID- 18637874
TI  - Comamonas testosteroni meningitis in a homeless man.
AB  - We report a case of meningitis caused by Comamonas testosteroni in a 54-year-old,
      alcoholic, homeless man. He, as a pedestrian, was struck by a car and suffered
      multiple fractures of the facial bones including the left frontal sinus. Over the
      course of 2-week hospitalization, he was clinically diagnosed with multiple
      cerebral and cerebellar infarcts resulting in altered mental status. He was
      pronounced dead 15 days after the injury. At the time of autopsy, diffuse
      purulent meningitis was found on gross examination. A swab culture of the brain
      surface was positive for C. Testosteroni, a saprophytic organism commonly found
      in soil and water. This is the first reported case of fatal meningitis caused by
      this micro-organism.

PMID- 18637875
TI  - Fatal renal hemorrhage after extracorporeal shock wave lithotripsy.
AB  - Renal hematoma is one of the most severe complications of extracorporeal shock
      wave lithotripsy (ESWL). ESWL is used in the noninvasive treatment of urinary
      calculosis. The shock waves can lead to capillary damage, renal parenchymal or
      subcapsular hemorrhage. We present a case with fatal complication and the result
      of the medico-legal evaluation. A 71-year-old woman was treated by ESWL, renal
      hematoma was detected during the clinical observation, and the patient died. The
      death occurred despite close clinical observation as a consequence of a rare
      complication of ESWL. The mechanism of death was hemorrhagic hypovolemic shock
      due to renal hemorrhage complications due to ESWL for treatment of renal calculi.
      This therapeutic complication is a known complication of appropriate treatment.

PMID- 18637876
TI  - Pacemaker/defibrillator evaluation at Los Angeles County Department of Coroner*.
AB  - Pacemakers and implantable cardioverter-defibrillators (ICDs) are implanted
      medical devices for the treatment of cardiac arrhythmias. These devices are now
      commonly encountered in the postmortem situation. The Los Angeles County
      Department of the Coroner uses the services of a cardiac electrophysiology
      consultant to interrogate pacemakers and ICDs, producing a detailed picture of
      the cardiac events recorded by the device. We have used this method to evaluate
      20 cases where the ICD or pacemaker provided significant information. We report
      four forensic cases to illustrate the different applications of pacemaker
      interrogation and its contribution in forensic investigation. This technique was
      used to establish identification of the decedent, to determine the cause and time
      of death, and to determine whether device malfunction could have played a role in
      the death. We conclude that detailed evaluation of the pacemaker or ICD in
      selected cases may provide essential information to the forensic pathologist.

PMID- 18637877
TI  - A rapid and robust sequence-based genotyping method for BoLA-DRB3 alleles in
      large numbers of heterozygous cattle.
AB  - The BoLA-DRB3 gene is a highly polymorphic major histocompatibility complex class
      II gene of cattle with over one hundred alleles reported. Most of the
      polymorphisms are located in exon 2, which encodes the peptide-binding cleft, and
      these sequence differences play a role in variability of immune responsiveness
      and disease resistance. However, the high degree of polymorphism in exon 2 leads
      to difficulty in accurately genotyping cattle, especially heterozygous animals.
      In this study, we have improved and simplified an earlier sequence-based typing
      method to easily and reliably genotype cattle for BoLA-DRB3. In contrast to the
      earlier method, which used a nested primer set to amplify exon 2 followed by
      sequencing with internal primers, the new method uses only internal primers for
      both amplification and sequencing, which results in high-quality sequence across
      the entire exon. The haplofinder software, which assigns alleles from the
      heterozygous sequence, now has a pre-processing step that uses a consensus of all
      known alleles and checks for errors in base calling, thus improving the ability
      to process large numbers of samples. In addition, advances in sequencing
      technology have reduced the requirement for manual editing and improved the
      clarity of heterozygous base calls, resulting in longer and clearer sequence
      reads. Taken together, this has resulted in a rapid and robust method for
      genotyping large numbers of heterozygous samples for BoLA-DRB3 polymorphisms.
      Over 400 Holstein-Charolais cattle have now been genotyped for BoLA-DRB3 using
      this approach.

PMID- 18637878
TI  - Association of an insulin-like growth factor 1 gene microsatellite with
      phenotypic variation and estimated breeding values of growth traits in Canchim
      cattle.
AB  - A population of 1398 Canchim (CA) cattle was genotyped to assess the association
      of an insulin-like growth factor 1 (IGF1) gene microsatellite with phenotypic
      variation and estimated breeding values of pre-weaning, weaning and post-weaning
      growth traits. After an initial analysis, the IGF1 genotype only had a
      significant effect (P < 0.05) on birth weight (BW) and weaning weight adjusted to
      240 days (WW240). For these two traits, direct and maternal breeding values were
      estimated using the restricted maximum likelihood (reml). Two analyses were
      carried out. In the first (Model I), all fixed effects were fitted. In the second
      (Model II), the fixed effect of the IGF1 genotype was omitted. The estimated
      genetic and phenotypic components of variance were similar for every trait in
      both models. For Model I, estimated direct and maternal heritabilities were 0.26
      and 0.16 for BW and 0.23 and 0.14 for WW240 respectively. The genetic and
      phenotypic correlations between BW and WW240 were 0.38 and 0.38 (Model I) and
      0.19 and 0.38 (Model II) respectively. Fifty animals were classified according to
      their direct and maternal breeding values for both traits. Spearman rank-order
      correlation between animal rankings in the two models was used to assess the
      effect of including the IGF1 genotype in the model. Non-significant values from
      this correlation were indicative of a difference in breeding value rankings
      between the two approaches. The IGF1 gene was found to be associated with
      phenotypic variation and breeding values in the early phase of growth.

PMID- 18637879
TI  - Calbindin D-28k, parvalbumin and calcitonin gene-related peptide immunoreactivity
      in the canine spinal cord.
AB  - This study was conducted as a comparative analysis of the immunohistochemical
      localization of calbindin D-28k, parvalbumin and the calcitonin gene-related
      peptide (CGRP) in the cervical through the sacral spinal cord of mongrel dogs, to
      reveal any distinct patterns of distribution and possible involvement in spinal
      processing. In laminae I and II of the substantia gelatinosa, both calbindin D
      28k and CGRP showed strong immunoreactivity, with calbindin D-28k being positive
      in both cells and fibres, while CGRP was positive in fibres only. Parvalbumin and
      CGRP immunoreactive cells were widely distributed in various nuclei and lower
      motor neurones in the ventromedial horn. In addition, the lower motor neurones
      expressed CGRP as well as parvalbumin, but not calbindin D-28k. These results are
      generally consistent with previous reports, and the co-localization of
      parvalbumin and CGRP may explain the functional improvement of lower motor neuron
      disease.

PMID- 18637880
TI  - Projections from the anterior interposed nucleus to the red nucleus diminish with
      age in the mouse.
AB  - To analyse the effect of ageing on the projection of the anterior interposed
      nucleus to the red nucleus, we injected the retrograde tracer fluorogold in the
      red nucleus of 3-, 6- and 12-month-old mice. The number of labelled neurones in
      the anterior interposed nucleus fell by 9% between 3 and 6 months and by another
      9% between 6 and 12 months (all P < 0.001). This suggests that loss of neurones
      from the cerebellar nuclei starts well before old age.

PMID- 18637881
TI  - Immunohistochemical study of 3 beta-hydroxysteroid dehydrogenase in dog's
      perianal sinus.
AB  - In this study, the localization of 3 beta-hydroxysteroid dehydrogenase (3beta
      HSD) activity in the wall of canine perianal sinus (PS) was determined. The 3
      beta-HSD activity was found out both in the cytoplasm of cells, situated in the
      propria and forming clusters adjacently to apocrine glands and in the cytoplasm
      of some epithelial cells in apocrine cells' glands. The results obtained about
      the 3 beta-HSD activity allowed us to propose a role of this enzyme in PS
      development and possibly, in tumourogenesis.

PMID- 18637882
TI  - Bovine lingual tonsil: histomorphological characteristics with special reference
      to the follicular dendritic cells.
AB  - In the bovine, the lingual tonsil is localized at the lingual radix. However, as
      the expansion of the tonsillar tissue was presumed to be much larger than the
      macroscopically visible part, selected specimens from the bovine tongue were
      examined to clarify if lymphatic tissue of the lingual tonsil was present rostral
      of a defined macroscopical landmark, i.e. rostral of the most caudal of the
      papillae vallatae. The identification of the lymphoreticular system was validated
      by means of the detection of reticulum cells, especially follicular dendritic
      cells (FDC). They characterize the tonsillar lymph nodules and distinguish them
      structurally from unspecific accumulations of lymphocytes. In our study, two
      monoclonal antibodies, i.e. CNA.42 and D46, detected bovine FDC cells in situ.
      'Organized' lymphoid tissue--i.e. solitary lymph nodules and aggregations of
      lymph nodules, both either with or without surrounding connective tissue, and
      with or without crypts, but with immunopositive reactions for FDC--could be
      observed up to 30 mm rostral of the most caudal of the papillae vallatae. As
      these formations were not identified macroscopically, they shall be referred to
      as the disseminate part of the lingual tonsil.

PMID- 18637883
TI  - Age-related three-dimensional morphological changes in rat motoneurons
      innervating diaphragm and longissimus muscles.
AB  - We investigated age-related morphological changes of rat motoneurons innervating
      diaphragm muscle (DI-MN) and lumber longissimus muscle (LL-MN) in which quite
      different activation patterns exist. In young (2-4 months) and old (24-26 months)
      rats, the motoneurons innervating both muscles were labelled retrogradely by
      intramuscular injection of cholera toxin B subunit. After a 4-day survival,
      horizontal slices of the spinal cord were processed with immunohistochemical
      staining (first antibody to cholera toxin B subunit and second antibody with Cy3)
      and observed with a confocal microscope. Three-dimensional reconstruction of
      labelled motoneurons was performed to examine soma and dendrite morphology. As
      compared to the soma volume in young rats, significantly smaller values were
      found in old rats in both motoneurons and the degrees of decline were 16.1% in DI
      MN and 20.3% in LL-MN. Significant decreases in the thickness of primary
      dendrites were also found in both motoneurons, and the degrees of decline were
      17.5% in DI-MN and 22.3% in LL-MN. Smaller changes were found in DI-MN than in LL
      MN, indicating the possibility that increased activation by central drives can
      attenuate age-related morphological changes of the motor system in the spinal
      cord.

PMID- 18637884
TI  - Cholesteryl ester transfer protein (CETP) genetic variation and early onset of
      non-fatal myocardial infarction.
AB  - Although Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of
      cholesteryl esters and triglycerides between lipoprotein particles and thus plays
      a crucial role in reverse cholesterol transport, the association of variations in
      the CETP gene with acute myocardial infarction (MI) remains unclear. In this
      study we examined whether common genetic variation in the CETP gene is related to
      early-onset non-fatal MI risk in a population-based case-control study from
      western Washington State. Genotyping for the CETP -2708 G/A, -971 A/G, -629 A/C,
      Intron-I TaqI G/A and exon-14 A/G (I405V) SNPs was performed in 578 cases with
      first acute non-fatal MI and in 666 demographically similar controls, free of
      clinical cardiovascular disease, identified randomly from the community. In
      person interviews and non-fasting blood specimens provided data on coronary heart
      disease risk factors. In men, there was little evidence for an association
      between single SNPs and MI risk, but in women the age- and race-adjusted OR was
      found to be significant in 4 out of the 5 CETP single variants. Haplotype
      analysis revealed two haplotypes associated with MI risk among men. As compared
      to men homozygous for the most common haplotype D (-2708 G, -971 G, -629 C, TaqI
      G and exon-14 A), the fully-adjusted multiplicative model identified haplotype G
      (-2708 G, -971 A, -629 A, TaqI G and exon-14 G) was associated with a 4.0-6.0
      fold increased risk of MI for each additional copy; [95%CI 2.4-14.8] and
      haplotype B (-2708 G, -971 G, -629 A, TaqI A and exon-14 A) showed a significant
      decreased risk for early onset MI [OR = 0.18; 95%CI 0.04 - 0.75]. An evolutionary
      based haplotype analysis indicated that the two haplotypes associated with the MI
      risk are most evolutionarily divergent from the other haplotypes. Variation at
      the CETP gene locus is associated with the risk of early-onset non-fatal MI. This
      association was found to be independent of HDL-C levels. These data and the sex
      specific findings require confirmation in other populations.

PMID- 18637885
TI  - Spontaneous hyphaema in a patient on warfarin treatment.

PMID- 18637886
TI  - Post-mortem clinical pharmacology.
AB  - Clinical pharmacology assumes that deductions can be made about the
      concentrations of drugs from a knowledge of the pharmacokinetic parameters in an
      individual; and that the effects are related to the measured concentration. Post
      mortem changes render the assumptions of clinical pharmacology largely invalid,
      and make the interpretation of concentrations measured in post-mortem samples
      difficult or impossible. Qualitative tests can show the presence of substances
      that were not present in life, and can fail to detect substances that led to
      death. Quantitative analysis is subject to error in itself, and because post
      mortem concentrations vary in largely unpredictable ways with the site and time
      of sampling, as a result of the phenomenon of post-mortem redistribution.
      Consequently, compilations of 'lethal concentrations' are misleading. There is a
      lack of adequate studies of the true relationship between fatal events and the
      concentrations that can be measured subsequently, but without such studies,
      clinical pharmacologists and others should be wary of interpreting post-mortem
      measurements.

PMID- 18637887
TI  - Population pharmacokinetic and pharmacodynamic analysis to support treatment
      optimization of combination chemotherapy with indisulam and carboplatin.
AB  - AIMS: Indisulam and carboplatin have shown synergistic activity in preclinical
      studies. In a dose escalation study of the combination, a treatment delay was
      frequently required in a 3-weekly regimen to allow recovery from myelosuppression
      from previous cycles. A 4-weekly regimen was better tolerated, but had a
      decreased dose-intensity which may compromise efficacy. The aims of this study
      were (i) to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to describe
      the myelosuppressive effect of the combination, and (ii) to use this model to
      select a dosing regimen for Phase II evaluation. METHODS: Sixteen patients were
      treated at four different dose levels of indisulam (1-h infusion on day 1) and
      carboplatin (30-min infusion on day 2). Pharmacokinetic data were analysed with
      nonlinear mixed effects modelling. A semiphysiological model describing
      chemotherapy-induced myelosuppression characterized the relationship between the
      pharmacokinetics and the haematological toxicity of indisulam and carboplatin. A
      simulation study was performed to evaluate the tolerability and dose-intensity
      for 3-weekly and 4-weekly treatment regimens. RESULTS: The PK-PD model described
      the pharmacokinetics and the myelosuppressive effect of indisulam and
      carboplatin. The risk of a treatment delay at cycle 2 due to myelosuppression was
      unacceptably high (34-65%) in a 3-weekly regimen for various dose levels (350-600
      mg m(-2) indisulam in combination with carboplatin to achieve an AUC of 4-6 mg
      min(-1) ml(-1)). This risk was acceptable for a 4-weekly regimen (9-24%), which
      is in line with the clinical study results. CONCLUSIONS: This PK-PD study
      supports the selection of indisulam 500 mg m(-2) and a dose of carboplatin to
      achieve an AUC of 6 mg min(-1) ml(-1) in a 4-weekly regimen as the recommended
      dose for future studies.

PMID- 18637888
TI  - Case ascertainment and estimated incidence of drug-induced long-QT syndrome:
      study in Southwest France.
AB  - AIMS: The aim of this study was to investigate the incidence and reporting rate
      of drug-induced long-QT syndrome (LQTS) in France [defined by evidence of
      torsades de pointes (TdP), QT prolongation and exposure to a relevant drug] and
      to assess feasibility of case collection for drug-induced LQTS. METHODS: A
      retrospective population-based study was carried out in Southwest France in five
      institutions: three main hospitals, one private clinic and one cardiac emergency
      unit, searched from 1 January 1999 to 1 January 2005 (population coverage of 614
      000). The study population consisted of 861 cases with International
      Classification of Diseases-10 diagnostic codes for ventricular tachycardia
      (I147.2), ventricular fibrillation (I149.0) and sudden cardiac death (I146.1)
      from hospital discharge summaries, supplemented by cases reported to national or
      regional pharmacovigilance systems, and voluntary reporting by physicians,
      validated according to internationally defined criteria for drug-induced LQTS.
      RESULTS: Of 861 patients coded with arrhythmias or sudden cardiac death, there
      were 40 confirmed surviving acquired cases of drug-induced LQTS. We estimated
      that the incidence of those who survive to reach hospital drug-induced LQTS is
      approximately 10.9 per million annually in France (95% confidence interval 7.8,
      14.8). CONCLUSIONS: Many cases of drug-induced LQTS may not survive before they
      reach hospital, as the reporting rate for drug-induced LQTS identified through
      the cardiology records and also reported to pharmacovigilance systems for the
      Midi-Pyrenees area is 3/40 (7.5%). Using the methods outlined it is possible to
      assemble cases to study genetic susceptibility to drug-induced LQTS and adapt
      these methods more widely.

PMID- 18637889
TI  - Pharmacist-led medication review: comment on Holland et al. 2008.

PMID- 18637891
TI  - Myopathies associated with red yeast rice and liquorice: spontaneous reports from
      the Italian Surveillance System of Natural Health Products.

PMID- 18637892
TI  - Early bioavailability of inhaled salbutamol reflects lung dose in children.

PMID- 18637893
TI  - Effect of atorvastatin on hs-CRP in acute coronary syndrome.
AB  - AIMS: To evaluate the effect of a lower dose (20 mg) of atorvastatin on hs-CRP
      concentrations in patients with ACS. METHODS: Group A (n = 50) patients received
      atorvastatin 20 mg day(-1) for 4 weeks in addition to standard anti-anginal
      treatment. Group B (n = 50) patients received standard anti-anginal treatment
      without atorvastatin. RESULTS: hs-CRP concentrations decreased in both groups,
      but the decrease was greater in group A. The decrease in hs-CRP was also
      significantly greater in the subgroups of smoking, hypertension and past history
      of cardiovascular disease with atorvastatin. CONCLUSIONS: The use of a lower dose
      (20 mg) of atorvastatin can offer an attractive approach for early treatment of
      patients with ACS.

PMID- 18637894
TI  - Serum leptin levels, skin leptin and leptin receptor expression in psoriasis.
AB  - BACKGROUND: Recent studies support the relation of psoriasis with obesity and
      cardiovascular disease. Leptin, a peptide hormone secreted predominantly from
      adipose tissue, is involved in the regulation of energy intake and expenditure.
      Recently, it has been shown to have several immunological effects including
      induction of proinflammatory cytokine production. OBJECTIVES: To investigate the
      possible role of leptin in psoriasis pathogenesis. METHODS: Forty-three patients
      with psoriasis, 10 diseased and 10 healthy controls with normal body mass index
      were included. Serum fasting leptin levels of the study group were examined by
      enzyme-linked immunosorbent assay. Tissue leptin and leptin receptor expression
      of both patients and controls were investigated by immunohistochemistry. RESULTS:
      Serum leptin levels, tissue leptin and leptin receptor expression were
      significantly higher in patients with severe psoriasis than patients with mild
      moderate psoriasis and controls (P < 0.05). Serum leptin levels showed a positive
      correlation with Psoriasis Area and Severity Index and involved body surface area
      in patients with psoriasis. In addition, serum leptin levels, tissue leptin and
      leptin receptor expression showed a positive correlation with disease duration in
      patients with psoriasis (P < 0.01, r = 0.979; P < 0.01, r = 0.691; P < 0.01, r =
      0.428, respectively). CONCLUSIONS: We assume that leptin might serve as a marker
      of severity in psoriasis and also may be a pathogenetic cofactor contributing to
      chronicity of the disease. Consequently, its role in obesity and cardiovascular
      disease in patients with psoriasis deserves to be studied. In addition, drugs
      targeting the proinflammatory effects of leptin may be a new adjuvant therapeutic
      approach in psoriasis.

PMID- 18637895
TI  - Brunsting-Perry cicatricial pemphigoid associated with autoantibodies to the C
      terminal domain of BP180.

PMID- 18637896
TI  - A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity
      syndrome.

PMID- 18637897
TI  - Psoriasis and chronic obstructive pulmonary disease: a case-control study.
AB  - BACKGROUND: Previous reports have demonstrated an association between psoriasis
      and the metabolic syndrome. Chronic obstructive pulmonary disease (COPD) has also
      been associated with the metabolic syndrome. OBJECTIVES: To assess the
      association between psoriasis and COPD in a population-based case-control study.
      METHODS: A case-control study was performed utilizing the database of Clalit
      Health Services, a large healthcare provider organization in Israel. Patients
      over the age of 20 years who were diagnosed with psoriasis ('cases') were
      compared with a sample of age- and gender-matched enrollees without psoriasis
      ('controls') regarding the prevalence of COPD. Group matching was performed. Data
      on health-related lifestyles and other comorbidities were collected. Chi(2)
      tests, t-tests and logistic regression models were used to compare between study
      groups. RESULTS: The study included 12,502 psoriasis cases and 24,287 controls.
      The prevalence of COPD was significantly higher in patients with psoriasis [5.7%
      vs. 3.6%, P < 0.001, odds ratio (OR) 1.63, 95% confidence interval (CI) 1.47
      1.81]. A multivariate logistic regression model demonstrated that psoriasis was
      significantly associated with COPD, after controlling for confounders, including
      age, sex, socioeconomic status, smoking and obesity (adjusted OR 1.27, 95% CI
      1.13-1.42, P < 0.001). CONCLUSIONS: In this large, population-based case-control
      study, psoriasis was found to be associated with COPD. Dermatologists caring for
      patients with psoriasis should be aware of this association, consult an internist
      or pulmonologist, and advise the patients to stop smoking and reduce additional
      risk factors for COPD.

PMID- 18637899
TI  - CD10 and CD34 in fetal and adult human hair follicles: dynamic changes in their
      immunohistochemical expression during embryogenesis and hair cycling.
AB  - BACKGROUND: CD10 and CD34 have been detected in both epithelial and mesenchymal
      components of anagen human hair follicles. OBJECTIVES: To analyse the expression
      of CD10 and CD34 in human hair follicle development as well as in different
      phases of the hair cycle. METHODS: Fetal and adult hair follicles at different
      stages of the hair cycle were examined by immunohistochemistry for CD10 and CD34.
      RESULTS: In fetal follicles, CD10 is expressed by the cells of the placodes, and
      CD34 by the mesenchymal cells of the dermal condensate. As the follicle matures,
      CD10 can be seen in the matrix cells, inner root sheath and dermal sheath. In
      adult follicles, the expression of CD10 in the follicular epithelium is present
      in anagen follicles, but tends to disappear in catagen, and is not detected in
      telogen. The CD10 positivity of the dermal sheath is more intense in catagen than
      in anagen follicles. CD34 immunostaining of the external root sheath was seen in
      adult anagen follicles but not in fetal follicles. This staining of the anagen
      outer sheath tends to disappear in catagen and is not detected in telogen.
      CONCLUSIONS: CD10 and CD34 are not proteins constantly present in a specific cell
      type of the hair follicle, but are proteins that can be expressed by both
      epithelial and mesenchymal cells depending on the stage of development and hair
      cycle. The distribution of the immunoreactivity to CD10 in the placode and CD34
      in the dermal condensate suggests a role of these proteins in initial stages of
      hair formation.

PMID- 18637898
TI  - A 4-year follow-up study of atopic dermatitis therapy with 0.1% tacrolimus
      ointment in children and adult patients.
AB  - BACKGROUND: For the treatment of a chronic disease like atopic dermatitis,
      sustained tolerability and efficacy of the applied medication are essential.
      OBJECTIVES: The present open-label, noncomparative study was conducted to obtain
      information on the long-term safety and efficacy of 0.1% tacrolimus ointment.
      METHODS: Patients aged 2 years or older with an affected body surface area of
      more than 5%, who previously participated in a clinical trial on tacrolimus
      ointment, were eligible for this study. The treatment area was defined by the
      investigator at study entry. Both children and adults applied continuously or
      intermittently 0.1% tacrolimus ointment twice daily during episodes of active
      disease plus an additional week after remission over a follow-up period of up to
      4 years. RESULTS: The intent-to-treat population comprised 782 patients, with a
      median age of 22 years (range 2-72). Patients remained in the study for up to 4
      years. Approximately half of the patients discontinued the study prematurely; the
      median follow-up was 1422 days. Median tacrolimus ointment use was 31.2 g during
      the first week; ointment use decreased during the first year and then remained
      stable for the remainder of the study. The median cumulative tacrolimus use was
      271.5 g at month 6, 462.5 g at month 12, 739.9 g at month 24, 1029.3 g at month
      36 and 1320.8 g at month 48. Altogether 51.8% of patients discontinued the study
      prematurely; the main reasons were withdrawal of consent (13.3%), loss to follow
      up (11.3%) and lack of efficacy (9.4%). Adverse events led to study
      discontinuation in 3.7% of the patients. The most frequent application site
      events were skin burning and pruritus. These events were most often reported in
      adult patients during the initial treatment period; prevalence decreased after
      the first week and remained at a low level throughout the study. Nonapplication
      site events occurred with stable incidences throughout the study period. In
      general, calculated daily hazard rates did not indicate an increased risk of
      adverse events with prolonged treatment. The total affected body surface area
      decreased substantially upon onset of treatment and efficacy of treatment was
      maintained until the end of the study with smaller but continuous improvements
      throughout the follow-up period. Overall, 75% of the patients and 76% of the
      investigators rated their satisfaction with the treatment as excellent, very good
      or good at the end of the study or at the time of premature discontinuation.
      CONCLUSIONS: The safety profile of intermittent or continuous long-term
      application of 0.1% tacrolimus ointment for up to 4 years was consistent with
      that which has been established from shorter studies and gave no reason for
      concern. In addition, 0.1% tacrolimus ointment demonstrated sustained efficacy as
      reflected by the expression of high satisfaction with treatment by both patients
      and investigators.

PMID- 18637900
TI  - Innervation and receptor profiles of the human apocrine (epitrichial) sweat
      gland: routes for intervention in bromhidrosis.
AB  - BACKGROUND: Human apocrine (epitrichial) sweat glands secrete in response to
      local or systemic administration of catecholamines and cholinergic agonists. As
      the process of secretion in human apocrine glands is not fully understood and no
      literature detailing the expression of adrenergic, cholinergic and purinergic
      receptors is available, there is a need to know the receptor types. Such data
      could provide new approaches for the treatment of axillary bromhidrosis.
      OBJECTIVES: To investigate the localization of nerve fibres, adrenergic,
      cholinergic and purinergic receptors in human axillary apocrine sweat glands by
      immunohistochemistry. METHODS: Human axillary apocrine sweat glands were
      investigated by serial sectioning of paraffin wax-embedded skin samples from
      volunteers. Sections were examined by light microscopy and immunohistochemistry,
      using antibodies against neurofilament, alpha- and beta-adrenoceptors, P2Y(1),
      P2Y(2) and P2Y(4) purinoceptors, and M(3) cholinoceptors. RESULTS: Neurofilaments
      were found near the eccrine but not the apocrine gland. Apocrine glands
      demonstrated the presence of beta-2 and beta-3 adrenoceptors in the secretory
      coil of the gland, but not alpha-1, beta-1 or M(3) receptors. Glandular
      purinergic staining (P2Y(1), P2Y(2) and P2Y(4)) was found in what looked like
      myoepithelial cells, while P2Y(1) and P2Y(2) staining was found on apical
      membranes and diffusely throughout secretory cells. Eccrine gland staining acted
      as internal positive controls. CONCLUSIONS: No nerve fibres were found near the
      apocrine gland, suggesting that any catecholamine influence is through humoral
      effects and that glands could be influenced by beta-adrenoceptor subtypes and
      purinoceptors. Blockage of both these types of receptors offers a route to
      controlling apocrine secretion from axillary glands and reducing the opportunity
      for the development of bromhidrosis.

PMID- 18637901
TI  - Gene expression profiles of meningiomas are associated with tumor cytogenetics
      and patient outcome.
AB  - Cytogenetic analysis is a powerful tool for predicting recurrence in meningiomas,
      even among histologically benign/grade I tumors. Despite this, no study has been
      reported in which the impact of tumor cytogenetics on the gene expression
      profiles (GEP) has been analyzed in meningiomas. Here, we analyzed the GEP of 47
      tumors and correlated them with the most clinical relevant cytogenetic subgroups
      of meningiomas, as confirmed through the analysis of 172 patients. Additionally
      three normal meningeal samples were also studied. Overall, our results show a
      clear association between the clinically relevant cytogenetic subgroups of
      meningiomas including diploid tumors (n = 18), isolated -22/22q- (n = 12),
      del(1p36) alone (n = 4) and complex karyotypes associated with del(1p36) and/or 
      14q (n = 13) and their GEP. Accordingly, based on the expression of 85 genes (40
      of which were coded in the altered chromosomes used for patient stratification)
      the cytogenetic class of the tumor could be predicted with an error of <1%, a
      clear association being found between the GEP and patient outcome (P = 0.03) but
      not tumor histopathology. In summary, we show a clear association between GEP of
      neoplastic cells and clinically relevant cytogenetic subgroups of meningiomas.

PMID- 18637902
TI  - Identifying blood donors willing to help with recruitment.
AB  - BACKGROUND AND OBJECTIVES: Social influence shapes behaviour and donors are
      ambassadors for blood banks. Donors are role models for family and friends and,
      therefore, so may be able to help with donor recruitment. MATERIALS AND METHODS:
      A questionnaire was used to assess donors' willingness to engage in donor
      recruitment. Measures included willingness to recruit new donors and antecedents
      of recruitment motivation based on the theory of planned behaviour (TPB).
      RESULTS: More than half of our participants were willing to try to recruit
      friends and family (57%). Self-efficacy was the most important correlate of
      intention to recruit as were cognitive attitude and experience with the blood
      bank. The findings suggest that the TPB provides a good basis for understanding
      cognitive antecedents of donors' willingness to recruit other donors. CONCLUSION:
      Results suggest that using existing donors to recruit new donors could be an
      efficient and cost-effective way to recruit additional donors. This approach
      warrants further investigation.

PMID- 18637903
TI  - Evolution of the multivesicular body ESCRT machinery; retention across the
      eukaryotic lineage.
AB  - Lysosomal targeting of ubiquitylated endocytic cargo is mediated in part by the
      endosomal sorting complex required for transport (ESCRT) complexes, a system
      conserved between animals and fungi (Opisthokonta). Extensive comparative genomic
      analysis demonstrates that ESCRT factors are well conserved across the eukaryotic
      lineage and complexes I, II, III and III-associated are almost completely
      retained, indicating an early evolutionary origin. The conspicuous exception is
      ESCRT 0, which functions in recognition of ubiquitylated cargo, and is restricted
      to the Opisthokonta, suggesting that a distinct mechanism likely operates in the
      vast majority of eukaryotic organisms. Additional analysis suggests that ESCRT
      III and ESCRT III-associated components evolved through a concerted model.
      Functional conservation of the ESCRT system is confirmed by direct study in
      trypanosomes. Despite extreme sequence divergence, epitope-tagged ESCRT factors
      TbVps23 and TbVps28 localize to the endosomal pathway, placing the trypanosome
      multivesicular body (MVB) in juxtaposition to the early endosome and lysosome.
      Knockdown of TbVps23 partially prevents degradation of an ubiquitylated
      endocytosed transmembrane domain protein. Therefore, despite the absence of an
      ESCRT 0 complex, the trypanosome ESCRT/MVB system functions similarly to that of
      opisthokonts. Thus the ESCRT system is an ancient and well-conserved feature of
      eukaryotic cells but with key differences between diverse lineages.

PMID- 18637905
TI  - Phylogeography and limited genetic connectivity in the endangered boring giant
      clam across the Coral Triangle.
AB  - The Coral Triangle is the global center of marine biodiversity; however, its
      coral reefs are critically threatened. Because of the bipartite life history of
      many marine species with sedentary adults and dispersive pelagic larvae,
      designing effective marine protected areas requires an understanding of patterns
      of larval dispersal and connectivity among geographically discrete populations.
      We used mtDNA sequence data to examine patterns of genetic connectivity in the
      boring giant clam (Tridacna crocea) in an effort to guide conservation efforts
      within the Coral Triangle. We collected an approximately 485 base pair fragment
      of mtDNA cytochrome c oxidase 1 (CO1) from 414 individuals at 26 sites across
      Indonesia. Genetic structure was strong between regions (phi(ST)=0.549, p <
      0.00001) with 3 strongly supported clades: one restricted to western Sumatra,
      another distributed across central Indonesia, and a third limited to eastern
      Indonesia and Papua. Even within the single largest clade, small but significant
      genetic structure was documented (phi(ST)=0.069, p < 0.00001), which indicates
      limited gene flow within and among phylogeographic regions. Significant patterns
      of isolation by distance indicated an average dispersal distance of only 25-50
      km, which is far below dispersal predictions of 406-708 km derived from estimates
      of passive dispersal over 10 days via surface currents. The strong regional
      genetic structure we found indicates potent limits to genetic and demographic
      connectivity for this species throughout the Coral Triangle and provides a
      regional context for conservation planning. The recovery of 3 distinct
      evolutionarily significant units within a well-studied taxonomic group suggests
      that biodiversity in this region may be significantly underestimated and that
      Tridacna taxa may be more endangered than currently recognized.

PMID- 18637906
TI  - Efficiency and concordance of alternative methods for minimizing opportunity
      costs in conservation planning.
AB  - Scarce resources and competing land-use goals necessitate efficient biodiversity
      conservation. Combining multicriteria analysis with conservation decision-support
      tools improves efficiency of conservation planning by maximizing outcomes for
      biodiversity while minimizing opportunity costs to society. An opportunity cost
      is the benefit that could have been received by taking an alternative course of
      action (i.e., costs to society of protecting an area for biodiversity rather than
      developing it for some other use). Although different ways of integrating
      multiple opportunity costs into conservation planning have been suggested, there
      have been no tests as to which method is most efficient. We compared the relative
      efficiency of 3 such procedures(Faith & Walker [1996], Sarkar et al. [2004], and
      a procedure of our own design) in a systematic conservation-planning framework
      for the Milne Bay Province of Papua New Guinea. We devised 14 opportunity costs
      and assigned these to 3 scenarios representing different conservation planning
      concerns: food security, macro-economic development, and biodiversity
      persistence. For each scenario, we compared the efficiency of the 3 methods in
      terms of amount of biodiversity protected relative to total expenditure for each
      opportunity cost. All 3 methods captured similar amounts of biodiversity, but
      differed in total cost. Our method had the least overall cost and was therefore
      most efficient. Nevertheless, there was a high correlation and geographical
      concordance among all 3 methods, indicating a high degree of spatial overlap.
      This suggests that choosing an appropriate approach may often depend on
      contextual factors related to the design of the planning question, rather than
      efficiency alone.

PMID- 18637904
TI  - Human herpesvirus-6 induces MVB formation, and virus egress occurs by an exosomal
      release pathway.
AB  - The final envelopment of most herpesviruses occurs at Golgi or post-Golgi
      compartments, such as the trans Golgi network (TGN); however, the final
      envelopment site of human herpesvirus 6 (HHV-6) is uncertain. In this study, we
      found novel pathways for HHV-6 assembly and release from T cells that differed,
      in part, from those of alphaherpesviruses. Electron microscopy showed that late
      in infection, HHV-6-infected cells were larger than uninfected cells and
      contained many newly formed multivesicular body (MVB)-like compartments that
      included small vesicles. These MVBs surrounded the Golgi apparatus. Mature
      virions were found in the MVBs and MVB fusion with plasma membrane, and the
      release of mature virions together with small vesicles was observed at the cell
      surface. Immunoelectron microscopy demonstrated that the MVBs contained CD63, an
      MVB/late endosome marker, and HHV-6 envelope glycoproteins. The viral
      glycoproteins also localized to internal vesicles in the MVBs and to secreted
      vesicles (exosomes). Furthermore, we found virus budding at TGN-associated
      membranes, which expressed CD63, adaptor protein (AP-1) and TGN46, and CD63
      incorporation into virions. Our findings suggest that mature HHV-6 virions are
      released together with internal vesicles through MVBs by the cellular exosomal
      pathway. This scenario has significant implications for understanding HHV-6's
      maturation pathway.

PMID- 18637907
TI  - Long-term dynamics of a fragmented rainforest mammal assemblage.
AB  - Habitat fragmentation is a severe threat to tropical biotas, but its long-term
      effects are poorly understood. We evaluated longer-term changes in the abundance
      of larger (>1 kg) mammals in fragmented and intact rainforest and in riparian
      "corridors" in tropical Queensland, with data from 190 spotlighting surveys
      conducted in 1986-1987 and 2006-2007. In 1986-1987 when most fragments were
      already 20-50 years old, mammal assemblages differed markedly between fragmented
      and intact forest. Most vulnerable were lemuroid ringtail possums (Hemibelideus
      lemuroides), followed by Lumholtz's tree-kangaroos (Dendrolagus lumholtzi) and
      Herbert River ringtail possums (Pseudocheirus herbertensis). Further changes were
      evident 20 years later. Mammal species richness fell significantly in fragments,
      and the abundances of 4 species, coppery brushtail possums (Trichosurus vulpecula
      johnstoni), green ringtail possums (Pseudochirops archeri), red-legged pademelons
      (Thylogale stigmatica), and tree-kangaroos, declined significantly. The most
      surprising finding was that the lemuroid ringtail, a strict rainforest
      specialist, apparently recolonized one fragment, despite a 99.98% decrease in
      abundance in fragments and corridors. A combination of factors, including long
      term fragmentation effects, shifts in the surrounding matrix vegetation, and
      recurring cyclone disturbances, appear to underlie these dynamic changes in
      mammal assemblages.

PMID- 18637909
TI  - Considering legal viability and societal values when deciding what to conserve
      under the U.S. Endangered Species Act.

PMID- 18637910
TI  - Funding priorities: big barriers to small-scale fisheries.

PMID- 18637911
TI  - Engaging recreational fishers in management and conservation: global case
      studies.
AB  - Globally, the number of recreational fishers is sizeable and increasing in many
      countries. Associated with this trend is the potential for negative impacts on
      fish stocks through exploitation or management measures such as stocking and
      introduction of non-native fishes. Nevertheless, recreational fishers can be
      instrumental in successful fisheries conservation through active involvement in,
      or initiation of, conservation projects to reduce both direct and external
      stressors contributing to fishery declines. Understanding fishers' concerns for
      sustained access to the resource and developing methods for their meaningful
      participation can have positive impacts on conservation efforts. We examined a
      suite of case studies that demonstrate successful involvement of recreational
      fishers in conservation and management activities that span developed and
      developing countries, temperate and tropical regions, marine and freshwater
      systems, and open- and closed-access fisheries. To illustrate potential benefits
      and challenges of involving recreational fishers in fisheries management and
      conservation, we examined the socioeconomic and ecological contexts of each case
      study. We devised a conceptual framework for the engagement of recreational
      fishers that targets particular types of involvement (enforcement, advocacy,
      conservation, management design [type and location], research, and monitoring) on
      the basis of degree of stakeholder stewardship, scale of the fishery, and source
      of impacts (internal or external). These activities can be enhanced by
      incorporating local knowledge and traditions, taking advantage of leadership and
      regional networks, and creating collaborations among various stakeholder groups,
      scientists, and agencies to maximize the probability of recreational fisher
      involvement and project success.

PMID- 18637912
TI  - Conservation goals and the relative importance of costs and benefits in reserve
      selection.
AB  - Including both economic costs and biological benefits of sites in systematic
      reserve selection greatly increases cost-efficiency. Nevertheless, limited
      funding generally forces conservation planners to choose which data to focus the
      most resources on; therefore, the relative importance of different types of data
      must be carefully assessed. We investigated the relative importance of including
      information about costs and benefits for 3 different commonly used conservation
      goals: 2 in which biological benefits were measured per site (species number and
      conservation value scores) and 1 in which benefits were measured on the basis of
      site complementarity (total species number in the reserve network). For each
      goal, we used site-selection models with data on benefits only, costs only, and
      benefits and costs together, and we compared the efficiency of each model. Costs
      were more important to include than benefits for the goals in which benefits were
      measured per site. By contrast, for the complementarity-based goal, benefits were
      more important to include. To understand this pattern, we compared the
      variability in benefits and in costs for each goal. By comparing the best and the
      worst possible selection of sites with regard to costs alone and benefits alone
      for each conservation goal, we introduced a simple and consistent variability
      measure that is applicable to all kinds of reserve-selection situations. In our
      study, benefit variability depended strongly on how the conservation goal was
      formulated and was largest for the complementarity-based conservation goal. We
      argue that from a cost-efficiency point of view, most resources should be spent
      on collecting the most variable type of data for the conservation goal at hand.

PMID- 18637914
TI  - Animal rights and conservation.

PMID- 18637915
TI  - Effects of illegal harvest of eggs on the population decline of leatherback
      turtles in Las Baulas Marine National Park, Costa Rica.
AB  - Within 19 years the nesting population of leatherback turtles (Dermochelys
      coriacea) at Parque Nacional Marino Las Baulas declined from 1500 turtles nesting
      per year to about 100. We analyzed the effects of fishery bycatch and illegal
      harvesting (poaching) of eggs on this population. We modeled the population
      response to different levels of egg harvest (90, 75, 50, and 25%) and the effect
      of eradicating poaching at different times during the population decline. We
      compared effects of 90% poaching with those of 20% adult mortality because both
      of these processes were present in the population at Las Baulas. There was a
      stepwise decline in number of nesting turtles at all levels of egg harvest.
      Extirpation times for different levels of poaching ranged from 45 to 282 years.
      The nesting population declined more slowly and survived longer with 20% adult
      mortality (146 years) than it did with 90% poaching (45 years). Time that elapsed
      until poaching stopped determined the average population size at which the
      population stabilized, ranging from 90 to 420 nesting turtles. Our model
      predicted that saving clutches lost naturally would restore the population when
      adult mortality rates were low and would contribute more to population recovery
      when there were short remigration intervals between nesting seasons and a large
      proportion of natural loss of clutches. Because the model indicated that poaching
      was the most important cause of the leatherback decline at Las Baulas, protecting
      nests on the beach and protecting the beach from development are critical for
      survival of this population. Nevertheless, the model predicted that current high
      mortality rates of adults will prevent population recovery. Therefore, protection
      of the beach habitat and nests must be continued and fishery bycatch must be
      reduced to save this population.

PMID- 18637916
TI  - Wood density as a conservation tool: quantification of disturbance and
      identification of conservation-priority areas in tropical forests.
AB  - Inventories of tree species are often conducted to guide conservation efforts in
      tropical forests. Such surveys are time consuming, demanding of expertise, and
      expensive to perform and interpret. Approaches to make survey efforts simpler or
      more effective would be valuable. In particular, it would be good to be able to
      easily identify areas of old-growth forest. The average density of the wood of a
      tree species is closely linked to its successional status. We used tree inventory
      data from eastern Borneo to determine whether wood density can be used to
      quantify forest disturbance and conservation importance. The average density of
      wood in a plot was significantly and negatively related to disturbance levels,
      with plots with higher wood densities occurring almost exclusively in old-growth
      forests. Average wood density was unimodally related to the diversity of tree
      species, indicating that the average wood density in a plot might be a better
      indicator of old-growth forest than species diversity. In addition, Borneo
      endemics had significantly heavier wood than species that are common throughout
      the Malesian region, and they were more common in plots with higher average wood
      density. We concluded that wood density at the plot level could be a powerful
      tool for identifying areas of conservation priority in the tropical rain forests
      of Southeast Asia.

PMID- 18637917
TI  - Protection of genetic diversity and maintenance of connectivity among reef corals
      within marine protected areas.
AB  - High-latitude coral reefs (HLRs) are potentially vulnerable marine ecosystems
      facing well-documented threats to tropical reefs and exposure to suboptimal
      temperatures and insolation. In addition, because of their geographic isolation,
      HLRs may have poor or erratic larval connections to tropical reefs and a reduced
      genetic diversity and capacity to respond to environmental change. On Australia's
      east coast, a system of marine protected areas (MPAs) has been established with
      the aim of conserving HLRs in part by providing sources of colonizing larvae. To
      examine the effectiveness of existing MPAs as networks for dispersal, we compared
      genetic diversity within and among the HLRs in MPAs and between these HLRs and
      tropical reefs on the southern Great Barrier Reef (GBR). The 2 coral species best
      represented on Australian HLRs (the brooding Pocillopora damicornis and the
      broadcast-spawning Goniastrea australensis) exhibited sharply contrasting
      patterns of diversity and connectedness. For P. damicornis, the 8-locus genetic
      and genotypic diversity declined dramatically with increasing latitude (N(a)= 3.6
      1.2, H(e)= 0.3-0.03, N(g):N = 0.87-0.06), although population structure was
      consistent with recruitment derived largely from sexual reproduction (G(o):G(e)=
      1.28-0.55). Genetic differentiation was high among the HLRs (F(ST)[SD]= 0.32
      [0.08], p < 0.05) and between the GBR and the HLRs (F(ST)= 0.24 [0.06], p <
      0.05), which indicates these temperate populations are effectively closed. In
      contrast for G. australensis, 9-locus genetic diversity was more consistent
      across reefs (N(a)= 4.2-3.9, H(e)= 0.3-0.26, N(g):N = 1-0.61), and there was no
      differentiation among regions (F(ST)= 0.00 [0.004], p > 0.05), which implies the
      HLRs and the southern GBR are strongly interconnected. Our results demonstrate
      that although the current MPAs appear to capture most of the genetic diversity
      present within the HLR systems for these 2 species, their sharply contrasting
      patterns of connectivity indicate some taxa, such as P. damicornis, will be more
      vulnerable than others, and this disparity will provide challenges for future
      management.

PMID- 18637918
TI  - Effects of an alien ant invasion on abundance, behavior, and reproductive success
      of endemic island birds.
AB  - Biological invaders can reconfigure ecological networks in communities, which
      changes community structure, composition, and ecosystem function. We investigated
      whether impacts caused by the introduced yellow crazy ant (Anoplolepis
      gracilipes), a pantropical invader rapidly expanding its range, extend to higher
      order consumers by comparing counts, behaviors, and nesting success of endemic
      forest birds in ant-invaded and uninvaded rainforest on Christmas Island (Indian
      Ocean). Point counts and direct behavioral observations showed that ant invasion
      altered abundances and behaviors of the bird species we examined: the Island
      Thrush (Turdus poliocephalus erythropleurus), Emerald Dove (Chalcophaps indica
      natalis), and Christmas Island White-eye (Zosterops natalis). The thrush, which
      frequents the forest floor, altered its foraging and reproductive behaviors in
      ant-invaded forest, where nest-site location changed, and nest success and
      juvenile counts were lower. Counts of the dove, which forages exclusively on the
      forest floor, were 9-14 times lower in ant-invaded forest. In contrast, counts
      and foraging success of the white-eye, a generalist feeder in the understory and
      canopy, were higher in ant-invaded forest, where mutualism between the ant and
      honeydew-secreting scale insects increased the abundance of scale-insect prey.
      These complex outcomes involved the interplay of direct interference by ants and
      altered resource availability and habitat structure caused indirectly by ant
      invasion. Ecological meltdown, rapidly unleashed by ant invasion, extended to
      these endemic forest birds and may affect key ecosystem processes, including seed
      dispersal.

PMID- 18637919
TI  - Abdominosacral resection is not related to the risk of neurological complications
      in patients with low-rectal cancer.
AB  - OBJECTIVE: Some authors claim that the risk of sacrectomy-related neurological
      complications is a serious limitation of abdominosacral resection (ASR). We
      determined the incidence of neurological complications in patients with a low
      rectal cancer who were treated by ASR. METHOD: The clinical records of 54
      consecutive patients with low-rectal cancer who were operated on by ASR were
      analysed. The occurrence of neurological complications in these patients was
      compared with that of 140 consecutive patients with cancer of the mid- and upper
      rectum who underwent anterior resection (AR) during the same period. Neurological
      complications were defined as bowel, bladder or sexual dysfunction, gait
      abnormalities and local parasthesiae persisting for more than 6 months following
      surgery. RESULTS: There were no persisting neurological complications after
      either AR or ASR. At the end of hospitalization, the 16 of 140 and 12 of 54 of
      those treated with AR and ASR had neurological complications, which fell to five
      of 140 and three of 53 at 3 months, respectively; at 6 months, no one treated had
      any complications. CONCLUSION: Neurological complications after AR and ASR were
      similar but recovery was complete at 6 months following surgery.

PMID- 18637920
TI  - The impact of pre- or postoperative radiochemotherapy on complication following
      anterior resection with en bloc excision of female genitalia for T4 rectal
      cancer.
AB  - OBJECTIVE: The aim of the study was to assess the mortality and morbidity
      following extended anterior resection with excision of internal female genitalia
      combined with pre- or postoperative chemoradiotherapy in women with extensive
      rectal cancer. METHOD: The study included a consecutive series of 21 women with
      T4 adenocarcinoma of the rectum infiltrating the reproductive organs treated with
      curative intent between 1997 and 2003. All patients had an extended anterior
      sphincter preserving resection of the rectum (total mesorectal excision) and
      hysterectomy with or without posterior vaginal wall excision. In all patients,
      surgery was combined with adjuvant radiochemotherapy. Ten patients received
      preoperative radiotherapy (50.4 Gy) concurrently with two courses of chemotherapy
      [fluorouracil with folinic acid (FA)] followed by surgery within 6-8 weeks and
      subsequently four courses of postoperative chemotherapy. Eleven received
      postoperative chemoradiotherapy (50.4 Gy plus fluorouracil with FA). RESULTS:
      There was no postoperative mortality. Postoperative complications were observed
      in 57% patients (early in 14% and late in 52%). These included: anterior
      resection syndrome with anorectal dysfunction in 52% (requiring proximal
      diversion in 5%), urinary complications in 24% (complete incontinence requiring a
      permanent catheter in 5%). In addition, postoperative acute bleeding requiring
      relaparotomy, delayed wound healing caused by superficial infection, anastomotic
      leakage, prolonged bowel paralysis, benign rectovaginal fistula and anastomotic
      stricture occurred (5% each). The risk of postoperative morbidity (52%) was
      similar for patients with or without preoperative radiochemotherapy. CONCLUSION:
      Despite this aggressive therapeutic approach, most postoperative complications
      were transient or could be treated. Preoperative radiochemotherapy did not
      increase the risk of morbidity.

PMID- 18637921
TI  - A rare complication of full-thickness rectal prolapse mimicking tumour.

PMID- 18637922
TI  - Efficacy of the anal fistula plug in complex anorectal fistulae.
AB  - OBJECTIVE: The treatment of complex anorectal and rectovaginal fistulae remains a
      difficult problem. The options are fistulotomy, setons, fibrin glue and a variety
      of flap procedures. Recently, there have been several reports of a new plug; the
      Surgisis AFP plug. Reports from various centres do not give consistent results.
      The aim of this study was to assess the efficacy of the Surgisis AFP fistula plug
      in a wide spectrum of patients with anorectal, rectovaginal and pouch vaginal
      fistulae. METHOD: Between March 2006 and September 2007, patients with a variety
      of anal fistulae were selected for fistula plug insertion in the coloproctology
      units at Leeds, UK, and Aarhus, Denmark. Demographic and fistulae details were
      obtained. Postoperatively, all patients had a course of oral antibiotics.
      RESULTS: Forty-three patients with a median age of 45 (range 18-65) years
      underwent a total of 45 procedures. Seventy-five per cent (n = 32) had a fistula
      secondary to cryptoglandular abscess. Median follow up was 47 (range 12-77)
      weeks. The success rate for complete healing was 44%. Dislodgement caused failure
      on 10 (22%) occasions. CONCLUSION: Our study shows a moderate success rate for
      treatment with fistula plugs. The complex nature of the fistulae selected may be
      the reason for the low success rate.

PMID- 18637923
TI  - Tailored surgery for internal and external rectal prolapse: functional results of
      268 patients operated upon by a single surgeon over a 21-year period*.
AB  - OBJECTIVE: Many procedures are used to treat internal (IRP) and external rectal
      prolapse (ERP). We report the outcome of surgery tailored in accordance with an
      evolving Unit algorithm over a 21-year period. METHOD: Two hundred and sixty
      eight patients (151 IRP and 117 ERP) are reported. Perineal procedures (Delorme's
      mucosectomy, Altemeier's perineal rectosigmoidectomy) were used in frail elderly
      patients with ERP with abdominal sacrorectopexy or the Frykman-Goldberg procedure
      in fit patients. In IRP, prolapsectomy was most common with anterior hemi
      Delorme's procedures for rectocele and levatorplasty for coincident faecal
      incontinence. Clinical and functional outcome was assessed over a median of 61
      months (range 4-184 months). RESULTS: Postoperative mortality was 0.4%. For ERP,
      a perineal procedure was carried out in 75 (61.4%) cases with a 7.2% complication
      rate, postoperative incontinence in 20 (26.7%), constipation in four (5.3%) and
      recurrence in 12 (16%). For 42 abdominal procedures, the complication rate was 5%
      with incontinence in 7.1%, constipation in eight (19%) and recurrence in five
      (11.9%). A perineal operation was used in 89.4% of patients with IRP with
      incontinence in 10.6%, persistent constipation in 48 (52.7%) and recurrence in 25
      (27.5%). The overall incontinence rate was 11% following abdominal and 24%
      following perineal procedures (P < 0.05). Recurrence of ERP was significantly
      higher following a perineal operation (P < 0.05). CONCLUSION: Tailored surgery
      for ERP achieves satisfactory results in terms of recurrence and functional
      outcome. For patients with IRP, perineal procedures are associated with a high
      incidence of recurrence and residual evacuatory difficulty.

PMID- 18637924
TI  - Comparison of the short-term results after Limberg and Karydakis procedures for
      pilonidal disease: randomized prospective analysis of 100 patients.
AB  - OBJECTIVE: The study was designed to compare the early postoperative results of
      the commonly used two surgical flap procedures in pilonidal disease: Karydakis
      and Limberg. METHOD: One hundred patients were randomized into two groups and
      standard Limberg or Karydakis procedures were performed. All had primary sinus
      orifices. Infected cases and the ones with secondary orifices over 2 cm distant
      from primary were excluded. Data were recorded concerning complications, need for
      analgesia and wound dressing, periods of time off work and off driving. Patients
      were asked to classify their first defecation manner after the operation and also
      pain according to a Visual Analogue Scale with range of 1-10. RESULTS: There was
      a significantly higher wound infection rate in the Karydakis group than in the
      Limberg group (13/50 and 4/50 respectively). This also resulted in significantly
      higher values for wound dressings and need for analgesia. The time off work and
      off driving and also the Visual Analogue Scale scores were not significantly
      different between the two groups. CONCLUSION: Both procedures can be safely
      performed in pilonidal disease with a standard length of stay in hospital and a
      similar loss of productive power. However, the Karydakis flap seems to have a
      significant higher infection rate and this probably increases the cost.

PMID- 18637925
TI  - The ideal lateral internal sphincterotomy: clinical and endosonographic
      evaluation following open and closed internal anal sphincterotomy.
AB  - OBJECTIVE: To evaluate the relationship between extent of internal sphincter
      division following open and closed sphincterotomy, as assessed by anal
      endosonography, with fissure persistence/recurrence and faecal incontinence.
      METHOD: A total of 140 consecutive patients undergoing lateral internal
      sphincterotomy (LIS) for idiopathic chronic anal fissure were prospectively
      studied. Preoperative clinical assessment was performed together with a
      postoperative clinical and endosonographic examination. Three zones of the
      internal sphincter, identifiable by endosonography, were used to describe the
      uppermost extent of LIS. Primary end-points were fissure persistence/recurrence
      and faecal incontinence. RESULTS: A total of 140 patients, median age 49.5 years
      (IQR: 38-56 years) were included. Seventy-five (53.6%) and 65(46.4%) patients
      underwent percutaneous LIS (PLIS) and open LIS (OLIS) respectively. Median follow
      up was 21 months (IQR: 14-29 months). Persistence and recurrence rates were 2.9%
      (4/140) and 5.7% (8/140) respectively. 7.9% (11/140) patients scored > 3 on the
      Jorge and Wexner Faecal Incontinence scale. PLIS was associated with a trend
      towards higher fissure persistence/recurrence rates than OLIS (12.0%vs 4.6%, P =
      0.141). OLIS was significantly associated with a higher proportion of complete
      sphincterotomies (CS) than PLIS (56/65 vs 48/75, P = 0.003). A CS was associated
      with a lower fissure persistence or recurrence rate (1/104 vs 11/36, P < 0.001)
      but higher incontinence scores (11/104 vs 0/36 cases with Wexner scores > 3, P =
      0.042) than following incomplete sphincterotomy. There was a strongly significant
      increase in incontinence scores (P < 0.001) and decrease in recurrence rates (P <
      0.001) with increasing length of sphincterotomy. CONCLUSION: We recommend a short
      and CS using either PLIS or OLIS for the treatment of idiopathic anal fissure.

PMID- 18637926
TI  - Application of the BSG guidelines to a colonoscopy waiting list.
AB  - Abstract Objective Currently priority for colonoscopy is given to diagnostic and
      therapeutic procedures. Surveillance colonoscopies place a significant demand on
      the service. These are held on a separate waiting list in our institution, which
      is currently several years behind. The purpose of this study was to apply the BSG
      guidelines to this waiting list in our institution in order to ascertain whether
      patients are appropriately listed. Method This was a retrospective review. The
      patients on the waiting list whose procedures were due in 2004 and 2005 formed
      the study group. Information on demographics, previous colonoscopies, and
      indication was taken from the case notes. Results were analysed using Microsoft
      Excel. Results A total of 172 patients were overdue their colonoscopies. If the
      BSG guidelines were strictly adhered to, 49% of these patients were
      inappropriately listed. If applied less rigidly, 42% of patients should not have
      been on the list. The reasons for removal from the list were as follows: Thirty
      nine patients were older than the upper age limit, 23 had had clear colonoscopies
      after adenomatous polyp follow up, four were listed for diverticular disease
      follow up, four for metaplastic polyps, one for constipation and one for per
      rectum (PR) bleed follow up. Conclusion With strict application of the BSG
      guidelines to a surveillance colonoscopy waiting list, 49% of the patients on the
      list do not need the procedure. It is recommended that consultant led education
      and control of the waiting list be used to reduce unnecessary investigations.

PMID- 18637927
TI  - Comparison of preoperative whole-body positron emission tomography with MDCT in
      patients with primary colorectal cancer.
AB  - OBJECTIVE: Preoperative use of emission tomography with(18)F-fluorodeoxyglucose
      (FDG-PET) in patients with primary colorectal cancer remains controversial. This
      study evaluated the additional value of FDG-PET in comparison with routine
      multidetector row computed tomography (MDCT) in patients with primary colorectal
      cancer. METHOD: Retrospective analysis was performed in 65 patients with
      colorectal cancer who underwent whole-body FDG-PET. Results of FDG-PET were
      compared with routine preoperative evaluation by MDCT regarding detection of
      primary tumour, lymph node involvement and distant metastases. All images were
      evaluated before surgery. RESULTS: Tumour detection rate was 100% (63/63) for
      MDCT and 98% (62/63) for FDG-PET. Lymph node involvement was pathologically
      confirmed in 35 patients. MDCT and FDG-PET displayed sensitivities of 89% (31/35;
      95% CI: 73-97%) and 43% (15/35; 95% CI: 26-61%) and specificities of 52% (11/21;
      95% CI: 30-74%) and 95% (20/21; 95% CI: 76-100%), respectively. Liver metastases
      were present in 22 patients. MDCT and FDG-PET showed accuracies of 98% (64/65;
      95% CI: 92-100%) and 97% (63/65; 95% CI: 89-100%), respectively. FDG-PET detected
      additional extrahepatic metastatic lesions and affected treatment plan compared
      with MDCT in 10 patients. CONCLUSION: Preoperative FDG-PET is not superior to
      MDCT for detection of primary tumour, lymph node involvement or liver metastases,
      but may have potential clinical value in patients with advanced colorectal cancer
      by detecting extrahepatic distant metastases.

PMID- 18637928
TI  - Preservation of sexual and bladder function after laparoscopic rectal surgery.
AB  - BACKGROUND: There have recently been reports of higher levels of bladder and
      sexual dysfunction in men after laparoscopic rectal surgery when compared with
      those undergoing open surgery. This has led some surgeons to question the role of
      the laparoscopic approach to rectal surgery. METHOD: This study represents a
      retrospective analysis of a prospectively collected database for a single unit,
      comprising 2406 patients undergoing laparoscopic colorectal surgery. Bladder
      function, potency and ejaculation were assessed at postoperative clinic visits
      for men undergoing laparoscopic low or ultra-low anterior resection and
      abdominoperineal excision of the rectum. RESULTS: A total of 101 males were
      identified (median age 62 years: range 20-90 years). Urinary dysfunction was
      reported by six (6%) patients. Six (6%) patients had sexual dysfunction,
      manifesting as retrograde ejaculation in four patients and erectile dysfunction
      in a further two patients. CONCLUSIONS: The low rates of sexual dysfunction in
      this unit may be attributable to pelvic dissection only being undertaken by
      experienced, dedicated laparoscopic colorectal surgeons. Laparoscopic restorative
      surgery for rectal cancer has been performed here only since 2001 after
      considerable experience accrued in operating on benign rectal disease and colon
      cancer. Studies from elsewhere reporting poorer functional outcomes have probably
      included a significant number of patients on the surgeons''learning curve'.

PMID- 18637929
TI  - V-Y Bilateral gluteus maximus myocutaneous advancement flap in the reconstruction
      of large perineal defects after resection of pelvic malignancies.
AB  - OBJECTIVE: To evaluate the role of the V-Y bilateral gluteus maximus myocutaneous
      flap (GLM) in the reconstruction of large perineal defects after wide surgical
      resections for pelvic malignancies. METHOD: Twelve consecutive patients (seven
      females and five males), of mean age 59 years (36-78), with primary or recurrent
      pelvic malignancies (rectal, anal and vulvar carcinoma), underwent either
      abdomino-perineal rectum excision with partial sacrectomy or total pelvic
      exenteration. The perineal defect was reconstructed by means of a GLM flap. Intra
      operative blood loss, operative time, hospital stay, postoperative complications
      and long-term outcome were retrospectively assessed. RESULTS: One patient died
      postoperatively. All the remaining patients had at least one early and/or late
      complication. After a mean follow-up of 31.2 months, seven patients were alive.
      No major functional impairment in daily activities was observed. Five patients
      experienced a slight discomfort in either walking, sitting or cycling.
      CONCLUSION: Gluteus maximus myocutaneus flap is a useful technique for the repair
      of perineo-pelvic defects after abdomino-perineal rectum excision with partial
      sacrectomy.

PMID- 18637930
TI  - Rectal cancer: involved circumferential resection margin - a root cause analysis.
AB  - INTRODUCTION: An involved circumferential resection margin (CRM) following
      surgery for rectal cancer is the strongest predictor of local recurrence and may
      represent a failure of the multidisciplinary team (MDT) process. AIM OF STUDY:
      The study analyses the causes of positive CRM in patients undergoing elective
      surgery for rectal cancer with respect to the decision-making process of the MDT,
      preoperative rectal cancer staging and surgical technique. METHOD: From March
      2002 to September 2005, data were collected prospectively on all patients
      undergoing elective rectal cancer surgery with curative intent. The data on all
      patients identified with positive CRM were analysed. RESULTS: Of 158 patients
      (male:female = 2.2:1) who underwent potentially curative surgery, 16 (10%)
      patients had a positive CRM on postoperative histology. Four were due to failure
      of the pelvic magnetic resonance imaging (MRI) staging scans to predict an
      involved margin, two with an equivocal CRM on MRI did not have preoperative
      radiotherapy, one had an inaccurate assessment of the site of primary tumour and
      in one intra-operative difficulty was encountered. No failure of staging or
      surgery was identified in the remaining eight of the 16 patients.
      Abdominoperineal resection (APR) was associated with a 26% positive CRM, compared
      with 5% for anterior resection. CONCLUSION: No single consistent cause was found
      for a positive CRM. The current MDT process and/or surgical technique may be
      inadequate for low rectal tumours requiring APR.

PMID- 18637931
TI  - Microsatellite and chromosomal stable colorectal cancers demonstrate poor
      immunogenicity and early disease recurrence.
AB  - OBJECTIVE: Colorectal cancers may demonstrate chromosomal instability (CSI) or
      microsatellite instability (MSI-H). A third group of microsatellite and
      chromosome stable (MACS) colorectal cancer has been described more recently.
      Patients with MSI-H colorectal cancers demonstrate improved outcome and a
      pronounced inflammatory infiltrate. Enhanced host immune response and increased
      immunogenicity might explain these observations. This study aims to further
      characterize colorectal cancer immunogenicity. METHOD: Microsatellite stability
      status was determined in resected tumour samples. Microsatellite stable (MSS)
      tumour samples were stratified by DNA ploidy status, as determined by flow
      cytometry into aneuploid MSS (CSI) and diploid MSS (MACS) cancers. Lymphocyte
      proliferation, quantified by bromodeoxyuridine incorporation assays assessed
      tumour protein immunogenicity and ELISA assays quantified inflammatory cytokine
      release. Kaplan-Meier survival curves and multivariate analyses were used to
      determine prognostic value. RESULTS: Patients with MSI-H colorectal cancer had
      improved outcome but those with MACS cancers undergoing curative surgery had
      significantly poorer disease-free survival (P = 0.002). The MACS phenotype was an
      independent predictor of poor outcome (HR = 2.44, 1.33-4.47, P = 0.004).
      Lymphocyte proliferation assays confirmed enhanced immunogenicity of MSI-H
      proteins and reduced immunogenicity of MACS proteins (P < 0.0001). In vitro
      levels of IFN-gamma (P = 0.004) and IL-18 (P < 0.0001) mirrored these differences
      in lymphocyte activity. CONCLUSIONS: Stratification of colorectal cancer by MSI
      and ploidy status may have prognostic value in patients undergoing curative
      surgery. MSI-H cancers display enhanced immunogenic properties but the immune
      response to MACS cancers appears to be absent and this may contribute to their
      poor prognosis.

PMID- 18637932
TI  - Stapled haemorrhoidopexy for the treatment of haemorrhoids: a systematic review.
AB  - OBJECTIVE: This systematic review aimed to evaluate the short- and long-term
      safety, efficacy and costs of stapled haemorrhoidopexy (SH) compared with
      conventional haemorrhoidectomy. METHOD: We searched 26 electronic databases and
      websites for studies in any language up to July 2006. Inclusion criteria were
      predefined, and each stage of the review process was conducted in duplicate.
      RESULTS: Twenty-seven randomized controlled trials were included (n = 2279). All
      had some methodological flaws. Postoperatively, 19 trials (95%) reported less
      pain, 17 (89%) reported a shorter operating time, 14 (88%) a shorter hospital
      stay, and 14 (93%) a shorter convalescence time following SH. However, prolapse
      was significantly more common after SH (OR 3.38; 95% CI: 1.00, 11.47). In the
      longer term, prolapse was significantly more common after SH (OR 4.34; 95% CI:
      1.67, 11.28) as was reintervention for prolapse (OR 6.78; 95% CI: 2.00, 23.00).
      There were no differences in the rate or type of complications. Conventional
      haemorrhoidectomy and SH had similar costs during the initial admission.
      CONCLUSION: Compared with conventional haemorrhoidectomy, SH resulted in less
      postoperative pain, shorter operating time, a shorter hospital stay, and a
      shorter convalescence, but a higher rate of prolapse and reintervention for
      prolapse.

PMID- 18637933
TI  - Comment on 'Surgical management of anal fistulae: a systematic review'.

PMID- 18637934
TI  - Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus
      2008.
AB  - OBJECTIVE: Our aim was to determine the range of neo-adjuvant therapy the
      multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal
      cancer. METHOD: A senior oncologist from each of the four oncology centres in
      north Wales and the north-west of England (approximate target population 8
      million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her
      understanding of the current evidence of neo-adjuvant therapy in rectal cancer.
      Then a representative from each centre was asked to identify which of three neo
      adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over
      five fractions and long-course chemoradiotherapy) he/she would use for a rectal
      cancer in the upper, middle or lower third of the rectum staged by magnetic
      resonance imaging as being T(2)-T(4) and/or N(0)-N(2). RESULTS: In all cases of
      locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four
      oncology centres recommended long-course chemoradiotherapy before rectal
      resection. This consensus was maintained for cases of lower third T(3a) N(0)
      cancers. Thereafter, the majority of patients with rectal cancer are offered
      adjuvant short-course radiotherapy. CONCLUSION: Neo-adjuvant therapy is less
      likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the
      upper third of the rectum.

PMID- 18637935
TI  - Injectable silicone biomaterial (PTQ) is more effective than carbon-coated beads
      (Durasphere) in treating passive faecal incontinence--a randomized trial.
AB  - OBJECTIVE: Both injectable silicone biomaterial (PTQ) and pyrolytic carbon-coated
      beads (Durasphere) have been shown to be effective in treating passive faecal
      incontinence due to internal sphincter dysfunction. This is a randomized study to
      evaluate their relative safety and efficacy. METHOD: Forty patients (mean age
      59.5 years vs 58.9 years) were randomized to have inter-sphincteric injection of
      PTQ or submucosal injection of Durasphere. Patients were assessed with anorectal
      physiology, endoanal ultrasound, a validated incontinence score and quality of
      life questionnaires. RESULTS: In the Durasphere group, complications included
      rectal pain (5%), erosion through rectal mucosa (10%), and type III
      hypersensitivity reaction (5%). No complications occurred in the PTQ group.
      Compared with PTQ, Durasphere group has a more rapid action, with improved
      continence at 2 weeks after injection. In both groups, faecal continence
      significantly improved 6 weeks after injection, and continued to improve
      significantly up to 6 months in both groups (P < 0.0001). At 6 weeks, 6 and 12
      months after injection, significantly more PTQ patients achieved greater than 50%
      improvement in Wexner's continence score than Durasphere patients (respectively,
      P = 0.01; P < 0.0001; P = 0.001). There was a significant improvement in faecal
      incontinence quality of life scale and the 12-month physical health scale of
      Short Form-12 health survey in the PTQ group but not in the Durasphere group.
      CONCLUSION: In patients with internal sphincter dysfunction, injectable silicone
      biomaterial was safer and more effective than Durasphere.

PMID- 18637936
TI  - Value of sacral nerve stimulation in the treatment of severe faecal incontinence:
      a comparison to the artificial bowel sphincter.
AB  - OBJECTIVE: Sacral nerve stimulation (SNS) is a recent treatment option in the
      management of severe faecal incontinence (FI) that offers promising results. The
      aim of this study was to compare SNS to artificial bowel sphincter (ABS)
      implanted patients to assess the rationale of this approach in achieving
      satisfying functional results and improved quality of life (QoL). METHOD: Among
      27 patients tested (December 2001 and April 2004), 15 patients were successfully
      managed with SNS. They were compared to 15 matched patients implanted with ABS in
      a previous period (control group). Assessment of continence level (Cleveland
      Clinic score), constipation score (Knowles, Eccersley, Scott Score) and QoL
      (Short-Form 36) were prospectively collected. RESULTS: Both groups were
      comparable for clinical parameters (age, gender, anal testing and aetiology of
      incontinence) and anal physiology. The mean postoperative continence score was
      significantly higher in the SNS group [9.4 (+/-3.3) vs 5.7 (+/-3.9), P < 0.01];
      however, the mean constipation score was higher in the ABS group (6.3 +/- 6.3 vs
      12.8 +/- 5.7, P < 0.01). The mean QoL score was similar in both groups. The mean
      follow-up after implantation was 15 (+/-9) months in the SNS group, and 43 (+/
      33) months in the ABS group. CONCLUSION: In this study, SNS offers satisfying
      results in terms of QoL, similar to that of ABS. Although it seems to be less
      effective in restoring continence level, symptoms of outlet obstruction are more
      frequent after ABS. This SNS approach should be proposed as a first-line
      treatment of FI in selected patients. ABS should remain an option that can
      improve function.

PMID- 18637937
TI  - To determine the efficacy of anal fistula plug in the treatment of high fistula
      in-ano: an initial experience.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy of the anal
      fistula plug in the treatment of high fistula-in-ano. METHOD: Twenty-three
      patients with high cryptoglandular fistula-in-ano were prospectively studied over
      1 year. The number of tracks, number of previous procedures and co-morbid
      conditions that could potentially affect outcome were noted. A seton was used to
      guide the AFP into the fistula track which was anchored at the primary opening.
      RESULTS: Two patients were lost to follow-up. Twenty-one patients (mean age was
      49.8 years) were followed from 192 to 543 days (median = 292 days). Thirteen
      patients had single track, eight had multiple tracks and 14 had a recurrent
      fistula. Success, defined by closure of all fistula tracks occurred in 71.4%
      (15/21). The success rate was 84.6% in patients with a single fistula track
      (11/13) compared with 50% in patients with multiple tracks (4/8) (P = 0.14,
      Fisher's exact test). Recurrent [10/14 (71.4%)] vs nonrecurrent fistulae [5/7
      (71.4%)] had no bearing on the outcome (P = 1.0). Two patients experienced
      healing despite extrusion of the plug in the early postoperative period. The
      procedure was safe and well tolerated. CONCLUSION: The Surgisis AFP was
      successful in 71.4% of patients. Plug extrusion does not necessarily mean
      failure.

PMID- 18637938
TI  - Treatment of left-sided colonic emergencies: a comparison of US and UK surgical
      practices.
AB  - BACKGROUND: Surgeons are increasingly considering resection and primary
      anastomosis when treating left-sided colonic obstruction or perforation in
      preference to the more traditional staged procedures. Previous studies in the
      United Kingdom (UK) and United States of America (USA) have suggested a greater
      interest in single-staged procedures amongst UK surgeons. This study was aimed to
      directly compare the treatment preferences between UK and US surgeons. METHOD: A
      questionnaire, designed to determine the procedure of choice when faced with left
      sided colonic emergencies in patients with good and poor anaesthetic risk, was
      sent to 500 surgeons in the UK and 500 surgeons in the USA. RESULTS: UK surgeons
      were more likely to perform resection, primary anastomosis and on-table colonic
      lavage in patients with sigmoid obstruction (good anaesthetic risk: P < 0.0001;
      poor risk: P < 0.01) and sigmoid perforation (good risk: P < 0.0001). In good
      risk patients with sigmoid obstruction, US surgeons were more likely than UK to
      choose Hartmann's procedure (P < 0.0001). US surgeons performing primary
      anastomosis were less likely to perform on-table lavage. CONCLUSION: Single-stage
      procedures are widely accepted as viable treatment options in both the UK and the
      USA when dealing with left-sided colonic emergencies. British surgeons are more
      likely to favour single-staged procedures, particularly with on-table colonic
      lavage, when compared with US surgeons.

PMID- 18637939
TI  - Gaucher disease diagnosed in a 30-year-old black man.

PMID- 18637940
TI  - Depression during pregnancy: the potential impact of increased risk for fetal
      aneuploidy on maternal mood.
AB  - Depression during pregnancy can have serious consequences for families.
      Indications of fetal aneuploidy can induce maternal stress, a risk factor for
      depression. Few studies have assessed symptoms of depression in pregnant women
      soon after they receive results indicating increased risk for fetal aneuploidy.
      We compared symptoms of depression in women who had increased risks for fetal
      aneuploidy with two other groups of pregnant women at similar gestational ages:
      controls, and women taking antidepressant medications (MEDS). Eighty-one women
      attending the British Columbia (BC) Medical Genetics (MG) Program regarding
      positive maternal serum screens or ultrasound soft marker findings completed the
      Edinburgh Postnatal Depression Scale (EPDS). Control (n = 41) and MEDS (n = 41)
      groups were recruited from the community or the BC Reproductive Mental Health
      program. A threshold score of 12 on the EPDS was used to calculate percentages of
      women likely to be depressed. Mean EPDS scores were compared using anova,
      followed by post-hoc tests. In the control, MG, and MEDS groups, 2.4%, 35%, and
      52.4% of women, respectively, scored above 12. Mean EPDS score was significantly
      higher in the MG group than in the control group (p < 0.0001). These results
      suggest a place for depression screening in prenatal genetic counseling.

PMID- 18637941
TI  - Huntington's disease-like 2 and apparent ancestry.

PMID- 18637942
TI  - A novel Phytophthora infestans haustorium-specific membrane protein is required
      for infection of potato.
AB  - Phytophthora infestans causes late-blight, a devastating and re-emerging disease
      of potato crops. During the early stages of infection, P. infestans
      differentiates infection-specific structures such as appressoria for host
      epidermal cell penetration, followed by infection vesicles, and haustoria to
      establish a biotrophic phase of interaction. Here we report the cloning, from a
      suppression subtractive hybridization library, of a P. infestans gene called
      Pihmp1 encoding a putative glycosylated protein with four closely spaced trans
      membrane helices. Pihmp1 expression is upregulated in germinating cysts and in
      germinating cysts with appressoria, and significantly upregulated throughout
      infection of potato. Transient gene silencing of Pihmp1 led to loss of
      pathogenicity and indicated involvement of this gene in the penetration and early
      infection processes of P. infestans. P. infestans transformants expressing a
      Pihmp1::monomeric red fluorescent protein (mRFP) fusion demonstrated that Pihmp1
      was translated in germinating sporangia, germinating cysts and appressoria,
      accumulated in the appressorium, and was located at the haustorial membrane
      during infection. Furthermore, we discovered that haustorial structures are
      formed over a 3 h period, maturing for up to 12 h, and that their formation is
      initiated only at sites on the surface of intercellular hyphae where Pihmp1::mRFP
      is localized. We propose that Pihmp1 is an integral membrane protein that
      provides physical stability to the plasma membrane of P. infestans infection
      structures. We have provided the first evidence that the surface of oomycete
      haustoria possess proteins specific to these biotrophic structures, and that
      formation of biotrophic structures (infection vesicles and haustoria) is
      essential to successful host colonization by P. infestans.

PMID- 18637943
TI  - Understanding informed consent for participation in international health
      research.
AB  - To participate in health research, there is a need for well-administered informed
      consent. Understanding of informed consent, especially in international health
      research, is influenced by the participants' understanding of information and the
      meaning attached to the information communicated to them regarding the purpose
      and procedure of the research. Incorrect information and the power differential
      between researcher and participants may lead to participants becoming victims of
      harmful research procedures. Meningitis epidemics in Kano in early 1996 led to a
      response from drug companies, especially Pfizer, as well as humanitarian workers
      from Medecins Sans Frontiers, which resulted in an unethical trial. Pfizer's drug
      trial during the epidemics has left a lasting controversy, which has yet to be
      resolved. This paper examines the key issues surrounding the controversy,
      discusses the context of informed decision-making, the ethical issues and
      implications of the incident, and concludes with some recommendations. Relevant
      texts, journals, Internet materials, newspaper articles and documentary materials
      on the conduct of the Pfizer's Trovan trial have been consulted. Four types of
      action (act intuitively, act rationally, act ignorantly, and act contextually -
      based on information provided) are identified as possible options for decision
      making. Participants most likely acted in ignorance due to poor understanding of
      the information contained in the verbal informed consent administered, thereby
      raising ethical issues. It is concluded that health research ethics committees
      have an important role to play nationally and locally in overseeing research, and
      in avoiding future occurrences.

PMID- 18637944
TI  - Ligand binding and antigenic properties of a human neonatal Fc receptor with
      mutation of two unpaired cysteine residues.
AB  - The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I
      related molecule that regulates the half-life of IgG and albumin. In addition,
      FcRn directs the transport of IgG across both mucosal epithelium and placenta and
      also enhances phagocytosis in neutrophils. This new knowledge gives incentives
      for the design of IgG and albumin-based diagnostics and therapeutics. To study
      FcRn in vitro and to select and characterize FcRn binders, large quantities of
      soluble human FcRn are needed. In this report, we explored the impact of two free
      cysteine residues (C48 and C251) of the FcRn heavy chain on the overall structure
      and function of soluble human FcRn and described an improved bacterial production
      strategy based on removal of these residues, yielding approximately 70 mg.L(-1)
      of fermentation of refolded soluble human FcRn. The structural and functional
      integrity was proved by CD, surface plasmon resonance and MALDI-TOF peptide
      mapping analyses. The strategy may generally be translated to the large-scale
      production of other major histocompatibility complex class I-related molecules
      with nonfunctional unpaired cysteine residues. Furthermore, the anti-FcRn
      response in goats immunized with the FcRn heavy chain alone was analyzed
      following affinity purification on heavy chain-coupled Sepharose. Importantly,
      purified antibodies blocked the binding of both ligands to soluble human FcRn and
      were thus directed to both binding sites. This implies that the FcRn heavy chain,
      without prior assembly with human beta2-microglobulin, contains the relevant
      epitopes found in soluble human FcRn, and is therefore sufficient to obtain
      binders to either ligand-binding site. This finding will greatly facilitate the
      selection and characterization of such binders.

PMID- 18637945
TI  - Huntington's disease: roles of huntingtin-interacting protein 1 (HIP-1) and its
      molecular partner HIPPI in the regulation of apoptosis and transcription.
AB  - Huntingtin protein (Htt), whose mutation causes Huntington's disease (HD),
      interacts with large numbers of proteins that participate in diverse cellular
      pathways. This observation indicates that wild-type Htt is involved in various
      cellular processes and that the mutated Htt alters these processes in HD. The
      roles of these interacting proteins in HD pathogenesis remain largely unknown. In
      the present review, we present evidence that Htt-interacting protein 1 (HIP-1),
      an endocytic protein, together with its interacting partner HIPPI, regulates
      apoptosis and gene expression, both processes being implicated in HD. Further
      studies are necessary to establish whether the HIPPI-HIP-1 complex or other
      interacting partners of HIPPI regulate apoptosis and gene expression that are
      relevant to HD.

PMID- 18637946
TI  - Huntington's disease: degradation of mutant huntingtin by autophagy.
AB  - Autophagy is a nonspecific bulk degradation pathway for long-lived cytoplasmic
      proteins, protein complexes, or damaged organelles. This process is also a major
      degradation pathway for many aggregate-prone, disease-causing proteins associated
      with neurodegenerative disorders, such as mutant huntingtin in Huntington's
      disease. In this review, we discuss factors regulating the degradation of mutant
      huntingtin by autophagy. We also report the growing list of new drugs/pathways
      that upregulate autophagy to enhance the clearance of this mutant protein, as
      autophagy upregulation may be a tractable strategy for the treatment of
      Huntington's disease.

PMID- 18637947
TI  - Huntington's disease: revisiting the aggregation hypothesis in polyglutamine
      neurodegenerative diseases.
AB  - After the successful cloning of the first gene for a polyglutamine disease in
      1991, the expanded polyglutamine tract in the nine polyglutamine disease proteins
      became an obvious therapeutic target. Early hypotheses were that misfolded,
      precipitated protein could be a universal pathogenic mechanism. However, new data
      are accumulating on Huntington's disease and other polyglutamine diseases that
      appear to contradict the toxic aggregate hypothesis. Recent data suggest that the
      toxic species of protein in these diseases may be soluble mutant conformers, and
      that the protein context of expanded polyglutamine is critical to understanding
      disease specificity. Here we discuss recent publications that define other
      important therapeutic targets for polyglutamine-mediated neurodegeneration
      related to the context of the expanded polyglutamine tract in the disease
      protein.

PMID- 18637948
TI  - Huntington's disease: a monogenic disorder with cellular and biochemical
      complexities.

PMID- 18637949
TI  - Variations in the mosquito larvicidal activities of toxins from Bacillus
      thuringiensis ssp. israelensis.
AB  - Comparing activities of purified toxins from Bacillus thuringiensis ssp.
      israelensis against larvae of seven mosquito species (vectors of tropical
      diseases) that belong to three genera, gleaned from the literature, disclosed
      highly significant variations in the levels of LC(50) as well as in the hierarchy
      of susceptibilities. Similar toxicity comparisons were performed between nine
      transgenic Gram-negative species, four of which are cyanobacterial, expressing
      various combinations of cry genes, cyt1Aa and p20, against larvae of four
      mosquito species as potential agents for biological control. Reasons for
      inconsistencies are listed and discussed. Standard conditions for toxin isolation
      and presentation to larvae are sought. A set of lyophilized powders prepared
      identically from six Escherichia coli clones expressing combinations of four
      genes displayed toxicities against larvae of three mosquito species, with levels
      that differed between them but with identical hierarchy.

PMID- 18637950
TI  - Biodiversity of amoebae and amoebae-resisting bacteria in a drinking water
      treatment plant.
AB  - The complex ecology of free-living amoebae (FLA) and their role in spreading
      pathogenic microorganisms through water systems have recently raised considerable
      interest. In this study, we investigated the presence of FLA and amoebae
      resisting bacteria (ARB) at various stages of a drinking water plant fed with
      river water. We isolated various amoebal species from the river and from several
      points within the plant, mostly at early steps of water treatment. Echinamoeba-
      and Hartmannella-related amoebae were mainly recovered in the drinking water
      plant whereas Acanthamoeba- and Naegleria-related amoebae were recovered from the
      river water and the sand filtration units. Some FLA isolates were recovered
      immediately after the ozonation step, thus suggesting resistance of these
      microorganisms to this disinfection procedure. A bacterial isolate related to
      Mycobacterium mucogenicum was recovered from an Echinamoeba-related amoeba
      isolated from ozone-treated water. Various other ARB were recovered using co
      culture with axenic Acanthamoeba castellanii, including mycobacteria, legionella,
      Chlamydia-like organisms and various proteobacteria. Noteworthy, a new
      Parachlamydia acanthamoebae strain was recovered from river water and from
      granular activated carbon (GAC) biofilm. As amoebae mainly multiply in sand and
      GAC filters, optimization of filter backwash procedures probably offers a
      possibility to better control these protists and the risk associated with their
      intracellular hosts.

PMID- 18637951
TI  - It's all relative: ranking the diversity of aquatic bacterial communities.
AB  - The study of microbial diversity patterns is hampered by the enormous diversity
      of microbial communities and the lack of resources to sample them exhaustively.
      For many questions about richness and evenness, however, one only needs to know
      the relative order of diversity among samples rather than total diversity. We
      used 16S libraries from the Global Ocean Survey to investigate the ability of 10
      diversity statistics (including rarefaction, non-parametric, parametric, curve
      extrapolation and diversity indices) to assess the relative diversity of six
      aquatic bacterial communities. Overall, we found that the statistics yielded
      remarkably similar rankings of the samples for a given sequence similarity cut
      off. This correspondence, despite the different underlying assumptions of the
      statistics, suggests that diversity statistics are a useful tool for ranking
      samples of microbial diversity. In addition, sequence similarity cut-off
      influenced the diversity ranking of the samples, demonstrating that diversity
      statistics can also be used to detect differences in phylogenetic structure among
      microbial communities. Finally, a subsampling analysis suggests that further
      sequencing from these particular clone libraries would not have substantially
      changed the richness rankings of the samples.

PMID- 18637952
TI  - Transient global amnesia and brain lesions: new hints into clinical criteria.
AB  - BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is the abrupt onset of
      anterograde amnesia with repetitive queries. Different hypotheses have been
      considered for its aetiology, but it still remains obscure. In 1990, Hodges and
      Warlow proposed clinical criteria for TGA. Applying these criteria, clinical
      studies looked for an unifying theory, considering TGA almost a primary and
      benign disorder. However, spare descriptions of TGA in patients with brain
      structural lesions have been reported. The aim of this study was to evaluate the
      prevalence of brain structural lesions among TGA patients. METHODS: One hundred
      and thirty clinically defined TGA were consecutively recruited. Among them, 13
      patients (10%) showed brain structural lesions (TGA-b). RESULTS: No significant
      difference in clinical features, duration of TGA episode, age of onset, gender
      between primary TGA (TGA-p) and TGA-b were found. Triggering factors were
      comparable, suggesting that TGA-b should be considered in the spectrum of TGA,
      being clinically indistinguishable. CONCLUSIONS: Transient global amnesia
      deserves a careful neuroimaging study and clinical follow-up considering the high
      prevalence of brain lesions among these patients and the impossibility to exclude
      TGA-b by clinical features. The follow-up of these patients and the evaluation of
      involved brain areas might help to further elucidate the pathogenetic mechanisms
      of the disease.

PMID- 18637954
TI  - CSF proteome analysis in multiple sclerosis patients by two-dimensional
      electrophoresis.
AB  - BACKGROUND AND PURPOSE: In recent years, different approaches have been used to
      investigate changes of cerebrospinal fluid (CSF) proteome in patients affected by
      multiple sclerosis (MS) with the aim to identify protein markers with potential
      diagnostic or prognostic value. Because of the lack of standardization of current
      proteomic techniques, contrasting results were achieved until now in different
      laboratories. In this study, we compare CSF proteome of 10 relapsing-remitting MS
      (RR-MS) patients, 11 patients with clinically isolated syndrome (CIS), and 10
      control subjects without neurological or systemic diseases. METHODS: The
      differential expression of CSF proteins amongst these cohorts of patients was
      investigated by using two-dimensional electrophoresis and mass spectrometry.
      RESULTS AND CONCLUSIONS: We found an overexpression of IgG free kappa light chain
      protein in both CIS and RR-MS patients, compared with control subjects and an
      increased expression of an apolipoprotein E isoform in RR-MS patients, compared
      with CIS and control groups. Our results confirm the presence of CSF proteome
      changes in MS patients. Future research should be aimed to investigate the role
      of these candidate CSF markers in larger cohorts of CIS and MS patients.

PMID- 18637953
TI  - Natural history of multiple sclerosis in a population-based cohort.
AB  - BACKGROUND AND PURPOSE: We sought to identify predictive clinical factors of
      disability during initial course in multiple sclerosis (MS) patients. METHODS: A
      total of 2871 MS patients from the LORSEP (Lorraine Multiple Sclerosis)
      population-based cohort were analyzed. The relationships between baseline
      demographic, clinical predictors and time to assignment of Expanded Disability
      Status Scale (EDSS) scores of 3, 4 and 6 were assessed using a Cox regression
      model. RESULTS: Multivariate analysis showed that, for relapsing-remitting
      patients, a shorter time to assignment of an EDSS score of 4 was associated with
      an older age of onset of MS and incomplete recovery from the first relapse.
      Median times were not influenced by gender or the time between the first two
      relapses. The results also demonstrated that MS progression is independent of the
      initial clinical data once an EDSS score of 4 is reached rather than a score of 3
      because the time from EDSS 3 to assignment of EDSS 4 were correlated with
      predicting variables. The data were very different for the time between
      assignment of scores of 4 and 6 because the median times were not influenced by
      any of the predicting variables.

PMID- 18637955
TI  - A novel presenilin 1 mutation (V261L) associated with presenile Alzheimer's
      disease and spastic paraparesis.
AB  - BACKGROUND AND PURPOSE: We report a novel mutation in exon 8 of the presenilin 1
      (PSEN1) gene (V261L) associated with early-onset autosomal dominant Alzheimer's
      disease and spastic paraparesis. METHODS AND RESULTS: The proband was a woman who
      developed insidious cognitive decline with predominant memory loss and gait
      disorder secondary to spasticity at the age of 40. Her brother and her mother had
      a similar disease in the fifth decade of life. The feature of amnestic
      presentation with spastic paraparesis is consistent with the majority of
      mutations in the exon 8 of the PSEN1 1 gene. CONCLUSIONS: Screening for PSEN1
      mutations is especially likely to be productive when directed toward persons with
      positive family history and with age at onset of under 60.

PMID- 18637956
TI  - TENS and optokinetic stimulation in neglect therapy after cerebrovascular
      accident: a randomized controlled study.
AB  - BACKGROUND: In a randomized controlled type Ib study, the effectiveness of three
      different forms of therapy for the treatment of visual neglect was assessed by
      comparing therapy outcomes in three groups of patients after cerebrovascular
      accidents. METHODS: A control group received only standard exploration training,
      whilst the second and third group received exploration training combined with
      either contralateral transcutaneous electrical nerve stimulation (TENS) or
      optokinetic stimulation (OKS) respectively. RESULTS: It was found that
      exploration training alone resulted in no improvement on both standard neglect
      tests (NTs) and everyday-relevant measures of reading and writing performance. In
      contrast, the groups receiving TENS or OKS showed significant improvements in
      both sets of measures with the difference that for the TENS group the improvement
      in NT scores at the end of therapy had disappeared 1-week later. However, both
      treatments resulted in significant improvements in reading and writing which were
      still present upon retesting 1-week after the end of therapy. CONCLUSION: Both
      methods can be recommended for neglect therapy and are superior to exploration
      therapy alone.

PMID- 18637957
TI  - Toxic hydrogen sulfide and dark caves: phenotypic and genetic divergence across
      two abiotic environmental gradients in Poecilia mexicana.
AB  - Divergent natural selection drives evolutionary diversification. It creates
      phenotypic diversity by favoring developmental plasticity within populations or
      genetic differentiation and local adaptation among populations. We investigated
      phenotypic and genetic divergence in the livebearing fish Poecilia mexicana along
      two abiotic environmental gradients. These fish typically inhabit nonsulfidic
      surface rivers, but also colonized sulfidic and cave habitats. We assessed
      phenotypic variation among a factorial combination of habitat types using
      geometric and traditional morphometrics, and genetic divergence using
      quantitative and molecular genetic analyses. Fish in caves (sulfidic or not)
      exhibited reduced eyes and slender bodies. Fish from sulfidic habitats (surface
      or cave) exhibited larger heads and longer gill filaments. Common-garden rearing
      suggested that these morphological differences are partly heritable. Population
      genetic analyses using microsatellites as well as cytochrome b gene sequences
      indicate high population differentiation over small spatial scale and very low
      rates of gene flow, especially among different habitat types. This suggests that
      divergent environmental conditions constitute barriers to gene flow. Strong
      molecular divergence over short distances as well as phenotypic and quantitative
      genetic divergence across habitats in directions classic to fish ecomorphology
      suggest that divergent selection is structuring phenotypic variation in this
      system.

PMID- 18637958
TI  - Patterns of host-plant choice in bees of the genus Chelostoma: the constraint
      hypothesis of host-range evolution in bees.
AB  - To trace the evolution of host-plant choice in bees of the genus Chelostoma
      (Megachilidae), we assessed the host plants of 35 Palearctic, North American and
      Indomalayan species by microscopically analyzing the pollen loads of 634 females
      and reconstructed their phylogenetic history based on four genes and a
      morphological dataset, applying both parsimony and Bayesian methods. All species
      except two were found to be strict pollen specialists at the level of plant
      family or genus. These oligolectic species together exploit the flowers of eight
      different plant orders that are distributed among all major angiosperm lineages.
      Based on ancestral state reconstruction, we found that oligolecty is the
      ancestral state in Chelostoma and that the two pollen generalists evolved from
      oligolectic ancestors. The distinct pattern of host broadening in these two
      polylectic species, the highly conserved floral specializations within the
      different clades, the exploitation of unrelated hosts with a striking floral
      similarity as well as a recent report on larval performance on nonhost pollen in
      two Chelostoma species clearly suggest that floral host choice is physiologically
      or neurologically constrained in bees of the genus Chelostoma. Based on this
      finding, we propose a new hypothesis on the evolution of host range in bees.

PMID- 18637959
TI  - Allee effect and self-fertilization in hermaphrodites: reproductive assurance in
      a structured metapopulation.
AB  - Reproductive assurance through selfing during colonization events or when
      population densities are low has often been put forward as a mechanism selecting
      for the evolution of self-fertilization. Such arguments emphasize on the role of
      both local demography and metapopulation processes. We developed a model for the
      evolution of self-fertilization in a structured metapopulation in which local
      densities are not steady because of population growth. Reproduction by selfing is
      density-independent (reproductive assurance) but selfed seeds endure inbreeding
      depression, whereas reproduction by outcrossing is density-dependent (Allee
      effect). First, we derived an analytical criterion for metapopulation viability
      as a function of the selfing rate and metapopulation parameters. We show that
      outcrossers can develop a viable metapopulation when they produce a high amount
      of dispersal seeds that counterbalances their incapacity to found new populations
      from low densities. Second, the model shows there is a positive feedback between
      demography and outcrossing rates, leading to either complete outcrossing or
      selfing. Specifically, we illustrate that inbreeding depression can paradoxically
      favor the evolution of selfing because of its negative effect on density. Also,
      complete outcrossing can be selected despite pollen limitation, although it does
      not provide a full seed set. This model underlines the influence of the mating
      system both on demography and gene dynamics in a metapopulation context.

PMID- 18637960
TI  - Natural selection reinforces speciation in a radiation of neotropical rainforest
      plants.
AB  - The importance of reinforcement, that is, natural selection that strengthens
      reproductive isolation between incipient species, remains controversial. We used
      two approaches to test for reinforcement in a species radiation of Neotropical
      gingers in the genus Costus. First, we conducted an intensive study of Costus
      pulverulentus and Costus scaber, two recently diverged species that co-occur and
      share hummingbird pollinators. The hummingbird pollinators transfer pollen
      between these Costus species, but hybrids are rarely found in nature. By
      performing pollinations between populations of C. pulverulentus and C. scaber
      from three sites across the species' geographic ranges, we find that pollen
      pistil incompatibilities acting prior to fertilization have evolved only between
      locally sympatric populations, whereas geographically distant populations within
      the region of sympatry and allopatric populations remain fully interfertile.
      Second, we conducted a comparative study of isolating mechanisms across the
      genus. We find lower seed set due to pollen-pistil incompatibility between
      species pairs that co-occur and experience pollen transfer in nature compared to
      species pairs that are otherwise isolated, regardless of genetic distance. Taken
      together, these studies indicate that crossing barriers prevent potentially
      maladaptive hybridization and effectively reinforce the speciation process. Our
      results add to mounting evidence for reinforcement from animal studies and show
      that plant speciation may also involve complex mate recognition systems.
      Reinforcement may be particularly important in rapidly diverging lineages where
      ecological factors play a primary role in reproductive isolation, as may often be
      the case in tropical communities.

PMID- 18637961
TI  - Evolutionary significance of imbalanced nuclear ratios within heterokaryons of
      the basidiomycete fungus Heterobasidion parviporum.
AB  - Many fungi have heterokaryotic life stages in which genetically different nuclei
      inhabit the same cell. In basidiomycetes, the heterokaryon is the product of
      mating and represents a genomic union very similar to a diploid thallus, yet the
      maintenance of unfused nuclei suggests a more complex association of the two
      genomes relative to diploidy. In species with variable numbers of nuclei per
      heterokaryotic cell, nuclear ratios within a mycelium may possibly become
      imbalanced (differ from 1:1) due to nuclear competition. In this study,
      heterokaryons of the basidiomycete Heterobasidion parviporum were examined to
      determine the effects of genotype and environment on nuclear ratios within
      vegetative mycelia. The data reveal that nuclear ratios are frequently
      imbalanced, generally stable over time, and genetically determined. The nuclear
      ratios were affected by environment, but the observed nuclear ratios did not
      follow the expectations of strong selection acting on a population of nuclei.
      Instead, these ratios were largely driven by genetic effects and epigenetic
      effects. Finally, the data suggest that nuclear ratio imbalance also affects both
      gene transcription and growth rate, implying that heterokaryotic basidiomycetes
      are not functionally equivalent to diploid individuals and have a higher
      potential for genotypic and phenotypic variation.

PMID- 18637962
TI  - Resource-mediated condition dependence in sexually dichromatic butterfly wing
      coloration.
AB  - Theory predicts that traits subject to strong sexual selection should evolve to
      be more exaggerated and developmentally integrated than nonsexual traits, thus
      leading to heightened condition dependence. Until recently, however, efforts to
      evaluate this prediction have suffered from either a purely correlational
      (nonmanipulative) approach, or from using manipulations of doubtful ecological
      relevance. Here I address these issues by integrating observation and
      manipulation to study condition- and sex-related color variation in a butterfly.
      The focal species, Eurema hecabe (Pieridae), possesses three sexually homologous
      and morphogenetically discrete dorsal wing color elements-coherently scattered
      ultraviolet (UV), pteridine yellow, and melaninic black. The UV is most strongly
      sexually selected, and is also the only color element with restricted
      distribution across female wings. Condition dependence and sexual dichromatism
      were pervasive, characterizing all color traits except the melanic black, and
      acting such that low condition males resembled high condition females. Although
      female coloration tended to exhibit greater phenotypic variation, size-scaled UV
      was more variable and condition dependent in males. Importantly, manipulation of
      larval resources was sufficient to closely reconstruct the extent and patterns of
      field-observed phenotypic variation in condition, and color trait expression,
      which implicates larval resource acquisition as a primary driver of condition
      dependence. These results support theories regarding phenotypic variation in
      sexually selected traits.

PMID- 18637963
TI  - Biostimulation and bioaugmentation to enhance dechlorination of polychlorinated
      dibenzo-p-dioxins in contaminated sediments.
AB  - Dechlorination of spiked 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TeCDD) was
      investigated in sediment microcosms from three polychlorinated dibenzo-p-dioxin
      and dibenzofuran (CDD/F)-contaminated sites: River Kymijoki, Finland; Gulf Island
      Pond, Maine; and Lake Roosevelt, Washington. Dechlorination was stimulated by
      addition of electron donor and halogenated priming compounds, and bioaugmentation
      by a mixed culture containing Dehalococcoides ethenogenes strain 195. Amendment
      with 1,2,3,4-tetrachlorobenzene (1,2,3,4-TeCB) promoted rapid dechlorination of
      1,2,3,4-TeCDD to 2-monochlorodibenzo-p-dioxin (2MCDD) in Gulf Island Pond and
      River Kymijoki sediments, however, only slow dechlorination to 1,4
      dichlorodibenzo-p-dioxin was observed in Lake Roosevelt sediments. The
      dechlorination pathway in 1,2,3,4-TeCB-amended microcosms proceeded mainly via
      1,3-dichlorodibenzo-p-dioxin, with less production of 2,3-dichlorodibenzo-p
      dioxin in comparison with other treatments. Microbial community analyses
      indicated that Dehalococcoides-like bacteria were enriched with 1,2,3,4-TeCB.
      Quantitative real-time PCR analysis of Dehalococcoides-specific 16S rRNA genes
      and the D. ethenogenes strain 195 dehalogenase gene, tceA, showed at least an
      order of magnitude higher gene copy numbers in the bioaugmented than in the
      nonbioaugmented microcosms. An active-dechlorinating population is present in the
      River Kymijoki and biostimulation may enhance both native Dehalococcoides spp.
      and the bioaugmented D. ethenogenes strain 195.

PMID- 18637964
TI  - Organic-matter degradative potential of Halomonas glaciei isolated from frazil
      ice in the Ross Sea (Antarctica).
AB  - Halomonas glaciei isolated from frazil ice in the Ross Sea (Antarctica) during
      austral summer 2003 was phenotypically characterized and its capability of
      degrading organic matter was tested. We evaluated specific bacterial growth rates
      (mu) to understand at which temperatures bacterial growth shows a linear and
      direct relationship with the available substrate (4-22 degrees C) and afterwards
      we tested H. glaciei growth curves and degradative potential at 0, 10 and 37
      degrees C using two different media (one enriched and one depleted in PO(4)). The
      strain grew exponentially only at 10 degrees C. The fastest hydrolysis rates were
      expressed by enzymes aimed at polysaccharide degradation (alpha-D-glucosidase,
      beta-D-glucosidase and beta-D-galactosidase) while alkaline phosphatase and
      aminopeptidase activities were rather low. Our data suggest a preferential demand
      for carbon derived from carbohydrates rather than from proteins: ectoenzyme
      activities transformed into carbon mobilization from organic polymers, showed
      that the total carbon potentially released from polysaccharides can be almost one
      order of magnitude higher than the protein carbon mobilization. Principal
      component analysis of the enzyme affinity separated the six experimental
      conditions, highlighting how different physical (temperature) and chemical (PO(4)
      enrichment or depletion) features actively lead to a differentiation in the
      efficiency of the ectoenzymes produced, resulting in preferential degradation of
      diverse kinds of organic substrates.

PMID- 18637965
TI  - Spatial and temporal heterogeneity of the bacterial communities in stream
      epilithic biofilms.
AB  - The spatial and temporal variability in bacterial communities within freshwater
      systems is poorly understood. The bacterial composition of stream epilithic
      biofilms across a range of different spatial and temporal scales both within and
      between streams and across the profile of individual stream rocks was
      characterised using a community DNA-fingerprinting technique (Automated Ribosomal
      Intergenic Spacer Analysis, ARISA). The differences in bacterial community
      structure between two different streams were found to be greater than the spatial
      variability within each stream site, and were larger than the weekly temporal
      variation measured over a 10-week study period. Greater variations in bacterial
      community profiles were detected on different faces of individual stream rocks
      than between whole rocks sampled within a 9-m stream section. Stream temperature
      was found to be the most important determinant of bacterial community variability
      using distance-based redundancy analysis (dbRDA) of ARISA data, which may have
      broad implications for riparian zone management and ecological change as a
      consequence of global warming. The combination of ARISA with multivariate
      statistical methods and ordination, such as multidimensional scaling (MDS),
      permutational manova and RDA, provided rapid and effective methods for
      quantifying and visualising variation in bacterial community structure, and to
      identify potential drivers of ecological change.

PMID- 18637966
TI  - Haemophilia care in China: achievements of a decade of World Federation of
      Hemophilia treatment centre twinning activities.
AB  - The World Federation of Hemophilia (WFH) began its involvement in China in 1993,
      supporting Chinese haemophilia centre twinning programmes in 1997. Although only
      three Chinese centres were in a twinning relationship (Tianjin/Calgary 1997-2004,
      Guangzhou/Ottawa 2000-2006, Shanghai/Ottawa, Calgary 2002-2007), WFH helped
      establish a collaborative network of six Chinese centres (Tianjin, Guangzhou,
      Shanghai, Beijing, Hefei, Jinan) in 2004. These network centres, in collaboration
      with haemophilia patients, shared and coordinated several successful ongoing
      priority projects (Registry, Nursing, Laboratory Diagnosis, Physiotherapy and
      Prophylaxis). A number of physicians, nurses and technologists have received WFH
      fellowships for training internationally. They are becoming haemophilia-care
      leaders and are key personnel working towards comprehensive care in China.
      National and regional workshops/conferences in addition to educational material
      development have been successful in reaching out to healthcare professionals and
      persons with haemophilia across the country. Key elements of success include the
      enthusiasm and commitment of the Chinese professionals and patient leaders in
      their desire to advance haemophilia care and their commitment to work
      collaboratively in a coordinated manner. They are beginning to gain national and
      international recognition and are launching outreach education and care
      programmes to cover other parts of China. WFH is now transitioning support in
      China from a twinning program to country programme (Global Alliance for
      Progress). Haemophilia work in China is still in the beginning, but there is now
      a solid foundation for future progress.

PMID- 18637967
TI  - Obesity: a new disaster for haemophilic patients? A nationwide survey.
AB  - The prevalence of obesity, an important risk factor for both cardiovascular
      disease and arthropathy, is strongly increasing in the general population, but
      data for the haemophilia population are scarce. Obesity may have a more profound
      effect on arthropathy and on cardiovascular disease in patients with haemophilia.
      To assess the prevalence of obesity in haemophilia patients and install adequate
      measures, if necessary. We performed a nationwide postal survey to measure the
      prevalence of overweight and obesity in Dutch haemophilia patients in 1992 (n =
      980) and 2001 (n = 1066). A random sample of the Dutch male population served as
      the control group. In adult haemophiliacs, the prevalence of overweight (BMI 25
      30 kg m(-2)) increased from 27% to 35% (95% CI 31.1-38.0) and the prevalence of
      obesity (BMI >/=30 kg m(-2)) doubled from 4% to 8% (95% CI 6.0-10.1), which was
      comparable with the general population. The increased prevalence of obesity in
      boys with haemophiliacs, which tripled in 10 years, is alarming. The increased
      prevalence of overweight and obesity in patients with haemophilia may have a
      profound effect on morbidity and quality of life of haemophilia patients by
      aggravating pre-existing arthropathy and predisposing aged patients to
      cardiovascular disease. Measures to prevent overweight in haemophiliacs are
      therefore urgently needed.

PMID- 18637968
TI  - Endometrial intraepithelial neoplasia is associated with polyps and frequently
      has metaplastic change.
AB  - AIMS: Endometrial intraepithelial neoplasia (EIN) is a monoclonal precursor to
      endometrioid endometrial adenocarcinoma characterized by a geographic cluster of
      crowded glands with epithelial cytology altered relative to the background. It
      may demonstrate epithelial metaplastic changes, or arise within polyps, but the
      frequencies of these features as encountered in practice is unknown. The aim was
      to report the epithelial differentiation state and polyp context of 83 sequential
      EIN lesions diagnosed over a 2-year period. METHODS AND RESULTS: EIN is a rare
      lesion, seen in only 1.4% of endometrial biopsy specimens in a busy hospital
      based practice. Of 83 EIN cases, 39 contained metaplastic changes (18% squamous
      morular, 14% tubal secretory and 5% each of secretory, mucinous or ciliated
      change). Endometrial polyps were more likely (odds ratio 5.2, P < 0.001) to occur
      in the endometrial biopsy specimens of women with EIN lesions (43.3%), compared
      with the background polyp rate (12.9%) of comparable specimens from the same
      patient population. CONCLUSIONS: Non-endometrioid differentiation and occurrence
      within polyps are frequent presentations of EIN lesions. Possible mechanisms of
      polyp association with EIN include: non-shedding of polyp tissue creating a
      shelter for persistence of pre-existing neoplastic glands, or promotion of
      premalignant glandular clones by unique polyp stroma.

PMID- 18637969
TI  - Skin biopsy for the diagnosis of peripheral neuropathy.
AB  - Skin biopsy has become an accepted tool for investigating small nerve fibres,
      which are invisible to conventional neurophysiological tests even though they are
      affected early on in peripheral neuropathies of varying aetiology. Morphometric
      analysis of epidermal and dermal nerves has proved to be reliable, reproducible
      and unaffected by the severity of neuropathy, making skin biopsy useful for
      diagnosing small fibre neuropathy (SFN) in clinical practice. The possibility of
      obtaining skin biopsy specimens from different sites of the body, to repeat them
      within the area of the same sensory nerve, to distinguish between somatic and
      autonomic nerves and to investigate the expression of nerve-related proteins has
      widened the potential applications of this technique to clinical research. Skin
      biopsy performed using a minimally invasive disposable punch is a safe and
      painless procedure. Using specific antibodies with bright-field
      immunohistochemistry or immunofluorescence technique, it is possible to
      investigate unmyelinated fibres innervating the epidermis of hairy and glabrous
      skin, large myelinated fibres supplying specialized corpuscles in glabrous skin,
      and autonomic fibres innervating sweat glands, blood vessels and arrector pilorum
      muscles. This review discusses the features of skin innervation in hairy and
      glabrous skin, the functional properties of skin nerve fibres and their changes
      in peripheral neuropathies.

PMID- 18637970
TI  - Cutaneous myxolipoma with apocrine glandular differentiation: description of a
      new clinicopathological variant with chromosome 6p21 rearrangement.

PMID- 18637971
TI  - Temperature and life history: experimental heating leads female tree swallows to
      modulate egg temperature and incubation behaviour.
AB  - 1. Life-history decisions are strongly affected by environmental conditions. In
      birds, incubation is energetically expensive and affected significantly by
      ambient temperature. We reduced energetic constraints for female tree swallows
      (Tachycineta bicolor) by experimentally heating nests during incubation by an
      average of 6.9 degrees C to test for changes in incubation behaviour. 2. Females
      in heated boxes (hereafter 'heated females') increased time spent incubating and
      maintained higher on-bout and off-bout egg temperatures. This indicates that
      female energetic constraints, not maximizing developmental conditions of
      offspring, determine incubation investment. Furthermore, this result suggests
      that embryonic developmental conditions in unmanipulated nests are suboptimal. 3.
      We found individual variation in how females responded to experimental heating.
      Early-laying (i.e. higher phenotypic quality) females with heated nests increased
      egg temperatures and maintained incubation constancy, while later-laying (lower
      quality) heated females increased incubation constancy. Changes in egg
      temperature were due to changes in female behaviour and not due directly to
      increases in internal nest-box temperatures. 4. Behaviour during the incubation
      period affected hatching asynchrony. Decreased variation in egg temperature led
      to lower levels of hatching asynchrony, which was also generally lower in heated
      nests. 5. Our study finds strong support for the prediction that intermittent
      incubators set their incubation investment at levels dictated by energetic
      constraints. Furthermore, females incubating in heated boxes allocated conserved
      energy primarily to increased egg temperature and increased incubation
      attentiveness. These results indicate that studies investigating the role of
      energetics in driving reproductive investment in intermittent incubators should
      consider egg temperature and individual variation more explicitly.

PMID- 18637972
TI  - Habitat destruction and metacommunity size in pen shell communities.
AB  - 1. In spatially structured communities, habitat destruction can have two effects:
      first, a main effect that occurs because of the loss of habitat area within a
      larger region, and a secondary effect due to changes in the spatial arrangement
      of local communities. Changes to the spatial arrangement can, in turn, affect the
      migration and extinction rates within local communities. 2. Our study involved
      the experimental destruction of entire local communities within larger regions in
      natural marine microcosms. Large and small arrays of dead pen shells were created
      in a shallow bay in north Florida, and the colonization by both encrusting and
      motile species on this empty substrate were followed through time. After most
      species had become established, half of the large arrays were perturbed to create
      small arrays by removal of half the shells, simulating habitat destruction. 3.
      After 48 days of further community development, comparisons of the large arrays,
      reduced arrays and original small arrays suggested that the mechanisms by which
      habitat destruction affects diversity could depend upon the size of the region
      affected and the natural history of the species being studied. 4. Habitat
      destruction reduced the diversity of motile species to a level lower than that
      found in the undisturbed small arrays, suggesting that the species that assembled
      in the original large metacommunities negatively influenced the species that
      occurred ultimately in the converted small arrays. 5. With sessile species,
      habitat destruction created richness levels that were intermediate to those of
      small and large arrays. The initial predestruction richness appears to have had a
      positive effect; because sessile species cannot disperse as adults, they may not
      respond to significant shifts in metacommunity size later in succession. Initial
      metacommunity size may be important for allowing individuals to select
      appropriate habitats before they settle.

PMID- 18637973
TI  - Understanding the impact of flooding on trait-displacements and shifts in
      assemblage structure of predatory arthropods on river banks.
AB  - 1. Species assemblages of naturally disturbed habitats are governed by the
      prevailing disturbance regime. Consequently, stochastic flood events affect river
      banks and the inhabiting biota. Predatory arthropods occupy predominantly river
      banks in relation to specific habitat conditions. Therefore, species sorting and
      stochastic processes as induced by flooding are supposed to play important roles
      in structuring riparian arthropod assemblages in relation to their habitat
      preference and dispersal ability. 2. To ascertain whether assemblages of spiders
      and carabid beetles from disturbed river banks are structured by stochastic or
      sorting mechanisms, diversity patterns and assemblage-wide trait-displacements
      were assessed based on pitfall sampling data. We tested if flooding disturbance
      within a lowland river reach affects diversity patterns and trait distribution in
      both groups. 3. Whereas the number of riparian spider species decreased
      considerably with increased flooding, carabid beetle diversity benefited from
      intermediate degrees of flooding. Moreover, regression analyses revealed trait
      displacements, reflecting sorting mechanisms particularly for spiders. Increased
      flooding disturbance was associated with assemblage-wide increases of niche
      breadth, shading and hygrophilic preference and ballooning propensity for spider
      (sub)families. Trait patterns were comparable for Bembidiini carabids, but were
      less univocal for Pterostichini species. Body size decreased for lycosid spiders
      and Bembidiini carabids with increased flooding, but increased in linyphiid
      spiders and Pterostichini carabids. 4. Our results indicate that mainly riparian
      species are disfavoured by either too high or too low degrees of disturbance,
      whereas eurytopic species benefit from increased flooding. Anthropogenic
      alterations of flooding disturbance constrain the distribution of common
      hygrophilous species and/or species with high dispersal ability, inducing shifts
      towards less specialized arthropod assemblages. River banks with divergent
      degrees of flooding impact should be maintained throughout dynamic lowland river
      reaches in order to preserve typical riparian arthropod assemblages.

PMID- 18637974
TI  - 5-Aminolevulininic acid photodynamic therapy treatment for tinea cruris caused by
      Trichophyton rubrum: report of 10 cases.

PMID- 18637975
TI  - Use of an optimized 1,2-indanedione process for the development of latent
      prints*.
AB  - 1,2-Indanedione belongs to a class of compounds which have demonstrated great
      potential in the processing of latent prints, particularly in the area of
      fluorescence. However, variability in results achieved worldwide has precluded it
      from being used extensively. In order to isolate the cause of this variability,
      various components of the formulation were analyzed, including purity level of
      the indanedione, type of carrier solvent, and the use of ZnCl(2) both as a
      secondary application and incorporated into the reagent. Using a resultant
      optimized formulation (Ind-Zn), performance comparisons were then made in the
      areas of visible color development, fluorescence, and degree of substrate
      staining with those of 1,8-diazafluoren-9-one (DFO) for both fresh and aged
      prints. Moisture content of the paper substrates on which the prints had been
      deposited was measured and a correlation found with percentage ambient relative
      humidity (% RH). Determination of visible color and fluorescence as it
      corresponded to percentage moisture content allowed for defining critical
      threshold levels necessary for achieving optimal results. Correlating these
      values with % RH then allowed for the development of standard operating
      procedures for obtaining best possible print development. Through this work, it
      was determined that a 7.4% v/v formulation of Ind-Zn having petroleum ether as a
      carrier solvent yielded the most optimal results when processing methods
      optimized for % RH in the laboratory were utilized. Both initial color
      development and fluorescence were superior to that of DFO; prints developed with
      Ind-Zn were a minimum of 6.5 units dE* darker and more red than with DFO for all
      substrates tested. Processing with Ind-Zn on the majority of the substrates
      examined yielded fluorescence intensity values approximately four times greater
      than with DFO.

PMID- 18637976
TI  - The use of material culture to establish the ethnic identity of victims in
      genocide investigations: a validation study from the American Southwest*.
AB  - Successful prosecution of genocide requires that the victims constitute one of
      four protected groups: national, religious, ethnic, or racial. Establishing
      victim identity in prior trials has relied on positive identification of
      decedents, been largely presumptive, or was based on untested methodology. This
      report details a validation study of one untested method: the use of material
      culture in establishing ethnic identity. Classes of clothing and personal effects
      were scored on 3,430 individuals of known Hispanic or White ancestry from autopsy
      records in New Mexico. Significant differences were seen in evidence of language,
      nationality, and religious affiliation between the two groups, as well as
      clothing types and currency. Predictive models used to estimate ethnic identity
      in random, blind subsets produced an overall accuracy of 81.5% and estimates of
      61-98% in specific subsets. Results suggest material culture, when present, can
      provide reliable evidence of ethnic affinity in genocide investigations.

PMID- 18637977
TI  - Extraction of alternative fuels from fire debris samples*.
AB  - Alternative fuels, specifically biodiesel, biodiesel blends, and E85 fuel, have
      been gaining a market share over the past few years. With the emergence of these
      fuels, fire debris analysts should be able to recognize their characteristics
      since these fuels may be encountered in casework. In this study, pure biodiesel
      (B100) and a 20% blend of pure biodiesel with petroleum diesel (B20) are examined
      as liquids and are extracted from debris samples using both passive headspace
      concentration and solvent extraction. Typical fire debris instrumental conditions
      are used to analyze these samples. Components of B100 and B20 may be observed in
      debris samples extracted using the passive headspace concentration method, but
      the chromatographic patterns are different from the pure liquid samples. When
      solvent extraction is used as a secondary extraction method on debris samples,
      the resulting patterns are consistent with the pure liquids of B100 and B20. E85
      fuel, a blend of 85% ethanol and 15% gasoline, can be extracted using a typical
      fire debris extraction technique but requires slight modifications to typical
      fire debris instrumental conditions. E85 is shown at various stages of
      evaporation to demonstrate the resiliency of the ethanol. Additionally, samples
      of E85 were placed on carpet, burned and extinguished to demonstrate the effects
      of the suppression medium on the retention of ethanol.

PMID- 18637978
TI  - Postmortem changes of human bodies on the bathyal sea floor--two cases of
      aircraft accidents above the open sea.
AB  - Forensic taphonomy in the marine context recently received growing attention.
      However, only limited information is available about the fate of human bodies at
      greater sea depth. Following two fatal aircraft accidents (west of Namibia, south
      of Sicily) human remains were recovered from a depth of 540-580 m (both cases)
      after 3 months (Namibia)/34 days (Sicily). In the Namibia case fully skeletonized
      bones were lifted. In the Sicily case a complete, dressed body was found
      exhibiting a partially skeletonized skull, starting adipocere formation and pink
      teeth. The rate and mode of decomposition of human bodies in the deep sea varies
      considerably and is mainly influenced by the local faunal composition. Of special
      relevance for the understanding of both cases was the oceanographic observation
      that the highly efficient necrophageous lyssianassids are abundant off Namibia
      but are rare in the Mediterranean, emphasizing the importance of collaboration of
      forensic and marine scientists in such case work.

PMID- 18637979
TI  - Resident-to-resident aggression in long-term care facilities: insights from focus
      groups of nursing home residents and staff.
AB  - OBJECTIVES: To more fully characterize the spectrum of resident-to-resident
      aggression (RRA). DESIGN: A focus group study of nursing home staff members and
      residents who could reliably self-report. SETTING: A large, urban, long-term care
      facility. PARTICIPANTS: Seven residents and 96 staff members from multiple
      clinical and nonclinical occupational groups. MEASUREMENTS: Sixteen focus groups
      were conducted. Content was analyzed using nVivo 7 software for qualitative data.
      RESULTS: Thirty-five different types of physical, verbal, and sexual RRA were
      described, with screaming or yelling being the most common. Calling out and
      making noise were the most frequent of 29 antecedents identified as instigating
      episodes of RRA. RRA was most frequent in dining and residents' rooms, and in the
      afternoon, although it occurred regularly throughout the facility at all times.
      Although no proven strategies exist to manage RRA, staff described 25 self
      initiated techniques to address the problem. CONCLUSION: RRA is a ubiquitous
      phenomenon in nursing home settings, with important consequences for affected
      individuals and facilities. Further epidemiological research is necessary to more
      fully describe the phenomenon and identify risk factors and preventative
      strategies.

PMID- 18637981
TI  - Self-reported health status of vietnamese and non-Hispanic white older adults in
      california.
AB  - Vietnamese Americans are a rapidly growing minority group in the United States,
      yet little is known about their health status. Chronic medical conditions and
      self-rated health of older Vietnamese Americans were compared with those of non
      Hispanic white adults living in California using the 2001 and 2003 California
      Health Interview Surveys (CHISs). The CHIS employed a random-digit-dial telephone
      survey, and its sample is representative of California's noninstitutionalized
      population. The sample included 359 Vietnamese and 25,177 non-Hispanic white
      adults aged 55 and older. Vietnamese and non-Hispanic white adults were compared
      in terms of limitations in activities of daily living, chronic medical conditions
      (diabetes mellitus, hypertension, heart disease, asthma), mental health care, and
      self-reported health, adjusting for age, sex, and education. Vietnamese were more
      likely than white participants to report needing help for mental health problems
      (adjusted odds ratio (aOR)=2.1, 95% confidence interval (CI)=1.4-3.1) but less
      likely to have had their medical providers discuss their mental health problems
      with them (aOR=0.3, 95% CI=0.1-0.5). In addition, Vietnamese participants
      reported significantly worse health than white adults on five of eight domains of
      the Medical Outcomes Survery 12-item Short Form survey (P<.006). Clinicians
      caring for older Vietnamese individuals should be aware of the high risk for
      mental health needs in this population and should initiate discussions about
      mental health with their patients. Further research is needed to better
      understand why older Vietnamese Americans are at higher risk for worse self
      reported health than older white adults.

PMID- 18637980
TI  - A prospective study of the effect of hypertension and baseline blood pressure on
      cognitive decline and dementia in postmenopausal women: the Women's Health
      Initiative Memory Study.
AB  - OBJECTIVES: To examine the relationship between baseline hypertension, blood
      pressure, and the development of cognitive decline in participants in the Women's
      Health Initiative Memory Study (WHIMS). DESIGN: Prospective analyses. SETTING:
      Thirty-nine centers. PARTICIPANTS: Seven thousand one hundred forty-nine women
      aged 65 and older. MEASUREMENTS: The Modified Mini-Mental State Examination (3MS)
      was used to assess global cognitive functioning. Participants who scored below
      pre-established cutpoints were scheduled for more-extensive neurocognitive
      assessments. Results from these assessments were centrally adjudicated. RESULTS:
      The mean age of this group of 7,149 participants at baseline was 71.0 +/- 3.8,
      and the mean 3MS score was 95.2 +/- 4.3. During a mean follow-up period of 4.5
      years, women without hypertension tended to have slightly higher 3MS scores than
      women with hypertension (P=.001), but the difference was not seen after
      adjustment for covariates (P=.17). Women with hypertension also appeared to be at
      greater risk for probable dementia or mild cognitive impairment (MCI) (hazard
      ratio=1.35, 95% confidence interval=1.07-1.70, P=.01), although when potential
      cofounders were accounted for, this association was no longer significant
      (P=.06). CONCLUSION: Hypertension and high blood pressure at baseline were not
      independently associated with MCI or probable dementia over time in older,
      cognitively intact, postmenopausal women enrolled in WHIMS after other potential
      confounders were taken into account. These analyses should not be viewed as
      discouraging appropriate medical treatment for hypertension.

PMID- 18637982
TI  - Healthcare cost differences with participation in a community-based group
      physical activity benefit for medicare managed care health plan members.
AB  - OBJECTIVES: To determine whether participation in a physical activity benefit by
      Medicare managed care enrollees is associated with lower healthcare utilization
      and costs. DESIGN: Retrospective cohort study. SETTING: Medicare managed care.
      PARTICIPANTS: A cohort of 1,188 older adult health maintenance organization
      enrollees who participated at least once in the EnhanceFitness (EF) physical
      activity benefit and a matched group of enrollees who never used the program.
      MEASUREMENTS: Healthcare costs and utilization were estimated. Ordinary least
      squares regression was used, adjusting for demographics, comorbidity, indicators
      of preventive service use, and baseline utilization or cost. Robustness of
      findings was tested in sensitivity analyses involving continuous propensity score
      adjustment and generalized linear models with nonconstant variance assumptions.
      RESULTS: EF participants had similar total healthcare costs during Year 1 of the
      program, but during Year 2, adjusted total costs were $1,186 lower (P=.005) than
      for non-EF users. Differences were partially attributable to lower inpatient
      costs (-$3,384; P=.02), which did not result from high-cost outliers. Enrollees
      who attended EF an average of one visit or more per week had lower adjusted total
      healthcare costs in Year 1 (-$1,929; P<.001) and Year 2 (-$1,784; P<.001) than
      nonusers. CONCLUSION: Health plan coverage of a preventive physical activity
      benefit for seniors is a promising strategy to avoid significant healthcare costs
      in the short term.

PMID- 18637983
TI  - Prevention of unintentional weight loss in nursing home residents: a controlled
      trial of feeding assistance.
AB  - OBJECTIVES: To determine the effects of a feeding assistance intervention on food
      and fluid intake and body weight. DESIGN: Crossover controlled trial. SETTING:
      Four skilled nursing homes (NHs). PARTICIPANTS: Seventy-six long-stay NH
      residents at risk for unintentional weight loss. INTERVENTION: Research staff
      provided feeding assistance twice per day during or between meals, 5 days per
      week for 24 weeks. MEASUREMENTS: Research staff independently weighed residents
      at baseline and monthly during a 24-week intervention and 24-week control period.
      Residents' food and fluid intake and the amount of staff time spent providing
      assistance to eat was assessed for 2 days at baseline and 3 and 6 months during
      each 24-week period. RESULTS: The intervention group showed a significant
      increase in estimated total daily caloric intake and maintained or gained weight,
      whereas the control group showed no change in estimated total daily caloric
      intake and lost weight over 24 weeks. The average amount of staff time required
      to provide the interventions was 42 minutes per person per meal and 13 minutes
      per person per between-meal snack, versus usual care, during which residents
      received, on average, 5 minutes of assistance per person per meal and less than 1
      minute per person per snack. CONCLUSION: Two feeding assistance interventions are
      efficacious in promoting food and fluid intake and weight gain in residents at
      risk for weight loss. Both interventions require more staff time than usual NH
      care. The delivery of snacks between meals requires less time than mealtime
      assistance and thus may be more practical to implement in daily NH care practice.

PMID- 18637984
TI  - Graph models for phenotype and genotype association between oral mucosa and
      submandibular gland tumorigenesis in rat.
AB  - BACKGROUND: In recent years, success of statistics in field of genetics has been
      the identification of genes that affect the process of disease. Experimental
      models using animals enable early stages of tumor development to be studied. The
      aim of this study was to apply graph models to assess the association between the
      observed phenotypic changes in rat oral mucosa and induced tumorigenesis in the
      submandibular gland (SMG). MATERIALS AND METHODS: We studied changes in oncogenes
      TP53 and bcl-2, histopathological and immunomarker variables in samples of oral
      mucosa and SMG of Wistar male rats, 60 days old and 180 g in weight, in which
      tumorigenesis was induced in their SMG by a 0.5% solution of 9,10-dimethyl-1,2
      benzanthracene in acetone. A set of linear structural equations were defined,
      with each formula indicating the response variables and the direct influences. In
      graph models, saliva was considered as a latent variable. The association was
      analyzed using Graphical Gaussian Markov models and odd ratios. RESULTS: About
      40% of animals treated with 9, 10-dimethyl-1, 2-benzanthracene showed
      histological alterations in the epithelial basal strata of their oral mucosa only
      at 150 days. Statistical models indicated a relationship between gene alteration
      in gene bcl-2 in the SMG and histological changes observed in the oral mucosa (P
      = 0.04). CONCLUSION: Graph statistical model with one latent variable allows to
      conclude that these results associated with other clinical parameters may be
      useful in detecting early changes in SMG tumorigenesis. Furthermore, the design
      of randomized sampling of oral mucosa allows to validate these results and
      establish a reliable methodology for presumptive diagnosis or screening in the
      future.

PMID- 18637985
TI  - Melatonin-evoked in vivo secretion of protein and amylase from the parotid gland
      of the anaesthetised rat.
AB  - The intravenous infusion of melatonin (5 and 25 mg/kg over 10 min) evoked a dose
      dependent output of protein and amylase but no overt fluid secretion from the
      parotid gland of the pentobarbitone-anaesthetised rat, as revealed by increased
      concentrations of protein and amylase activity in a subsequent wash-out flow of
      saliva in response to an intravenous bolus injection of methacholine (5
      microg/kg) 10 min later. The secretory responses to melatonin occurred in the
      presence of alpha- and beta-adrenoceptor antagonists. They were not affected by
      the cholecystokinin A-receptor antagonist, lorglumide, and they were reproduced
      in eviscerated animals acutely subjected to postganglionic sympathetic and
      parasympathetic denervation of the gland. The responses to melatonin were
      partially dependent on nitric oxide generation, through the activity of nitric
      oxide synthase of the neuronal type. Immunoblotting showed both melatonin
      receptors of type 1 and type 2 to be expressed in parotid gland tissue. The
      relative specific melatonin 2-receptor antagonist luzindole prevented the
      expected secretory effects of melatonin. The results favour a direct action by
      melatonin on melatonin receptors of parotid secretory cells and suggest a
      potential physiological role for melatonin in the regulation of salivary
      glandular activities.

PMID- 18637986
TI  - Melatonin as a negative mitogenic hormonal regulator of human prostate epithelial
      cell growth: potential mechanisms and clinical significance.
AB  - Circannual variation in the human serum levels of prostate-specific antigen, a
      growth marker of the prostate gland, has been reported recently. The present
      study was conducted to investigate the role of the photoperiodic hormone
      melatonin (MLT) and its membrane receptors in the modulation of human prostate
      growth. Expression of MT(1) and MT(2) receptors was detected in benign human
      prostatic epithelial tissues and RWPE-1 cells. MLT and 2-iodomelatonin inhibited
      RWPE-1 cell proliferation and up-regulated p27(Kip1) gene and protein expression
      in the cells. The effects of MLT were blocked by the nonselective MT(1)/MT(2)
      receptor antagonist luzindole, but were not affected by the selective MT(2)
      receptor antagonist 4-phenyl-2-propionamidotetraline. Of note, the
      antiproliferative action of MLT on benign prostate epithelial RWPE-1 cells was
      effected via increased p27(Kip1) gene transcription through MT(1) receptor
      mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in
      parallel, a signaling process which has previously been demonstrated in 22Rv1
      prostate cancer cells. Taken together, the demonstration of the
      MT(1)/PKA+PKC/p27(Kip1) antiproliferative pathway in benign and malignant
      prostate epithelial cell lines indicated the potential importance of this MLT
      receptor-mediated signaling mechanism in growth regulation of the human prostate
      gland in health and disease. Collectively, our data support the hypothesis that
      MLT may function as a negative mitogenic hormonal regulator of human prostate
      epithelial cell growth.

PMID- 18637987
TI  - Novel peptide ligands of RGS4 from a focused one-bead, one-compound library.
AB  - Regulators of G protein signaling accelerate GTP hydrolysis by G alpha subunits
      and profoundly inhibit signaling by G protein-coupled receptors. The distinct
      expression patterns and pathophysiologic regulation of regulators of G protein
      signaling proteins suggest that inhibitors may have therapeutic potential. We
      previously reported the design, mechanistic evaluation, and structure-activity
      relationships of a disulfide-containing cyclic peptide inhibitor of RGS4, YJ34
      (Ac-Val-Lys-c[Cys-Thr-Gly-Ile-Cys]-Glu-NH(2), S-S) (Roof et al., Chem Biol Drug
      Des, 67, 2006, 266). Using a focused one-bead, one-compound peptide library that
      contains features known to be necessary for the activity of YJ34, we now identify
      peptides that bind to RGS4. Six peptides showed confirmed binding to RGS4 by flow
      cytometry. Two analogs of peptide 2 (Gly-Thr-c[Cys-Phe-Gly-Thr-Cys]-Trp-NH(2), S
      S with a free or acetylated N-terminus) inhibited RGS4-stimulated G alpha(o)
      GTPase activity at 25-50 microM. They selectively inhibit RGS4 but not RGS7,
      RGS16, and RGS19. Their inhibition of RGS4 does not depend on cysteine
      modification of RGS4, as they do not lose activity when all cysteines are removed
      from RGS4. Peptide 2 has been modeled to fit in the same binding pocket predicted
      for YJ34 but in the reverse orientation.

PMID- 18637988
TI  - A small subset of signal peptidase residues are perturbed by signal peptide
      binding.
AB  - Perturbations of the chemical shifts of a small subset of residues in the
      catalytically active domain of Escherichia coli signal peptidase I (SPase I) upon
      binding signal peptide suggest the contact surface on the enzyme for the
      substrate. SPase I, an integral membrane protein, is vital to preprotein
      transport in prokaryotic and eukaryotic secretory systems; it binds and
      proteolyses the N-terminal signal peptide of the preprotein, permitting folding
      and localization of the mature protein. Employing isotopically labeled C-terminal
      E. coli SPase I Delta2-75 and an unlabeled soluble synthetic alkaline phosphatase
      signal peptide, SPase I Delta2-75 was titrated with the signal peptide and 2D
      (1)H-(15)N heteronuclear single-quantum correlation nuclear magnetic resonance
      spectra revealed chemical shifts of specific enzyme residues sensitive to
      substrate binding. These residues were identified by 3D HNCACB, 3D CBCA(CO)NH,
      and 3D HN(CO) experiments. Residues Ile80, Glu82, Gln85, Ile86, Ser88, Gly89,
      Ser90, Met91, Leu95, Ile101, Gly109, Val132, Lys134, Asp142, Ile144, Lys145, and
      Thr234, alter conformation and are likely all in, or adjacent to, the substrate
      binding site. The remainder of the enzyme structure is unperturbed. Ramifications
      for conformational changes for substrate docking and catalysis are discussed.

PMID- 18637989
TI  - Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel
      precursor-analogues.
AB  - Glycosylphosphatidylinositol precursor-analogues were synthesized in which the
      natural diacylglycerol lipid was replaced with either of two steroidal moieties.
      The ability of the steroidal glycosylphosphatidylinositol precursor-analogues to
      prime the glycosylphosphatidylinositol biosynthetic pathway was assessed in a
      trypanosomal cell-free system. The N-acetyl-D-glucosaminylphosphatidylinositol de
      N-acetylase was only able to act upon the N-acetylglucosamine form of one of the
      two analogues. However, the glucosamine form of both analogues could be
      mannosylated, but neither were inositol-acylated nor modified with ethanolamine
      phosphate. The use of alternative groups, such as sterols, in place of the
      natural diacylglycerol lipid may enable the production of more drug-like,
      substrate-based inhibitors.

PMID- 18637990
TI  - On application of constitutional descriptors for merging of quinoxaline data sets
      using linear statistical methods.
AB  - The present paper is an attempt for unifying two different quinoxaline data sets
      with a wide range of substituents in 2, 3, 7, and 8 positions having excellent
      antitubercular activities with a view to developing robust and reliable structure
      activity relationships. The merging has been performed for these two sets of
      quinoxaline 1,4-di-N-oxides derivatives comprising 29 and 18 compounds,
      respectively, on the basis of constitutional descriptors, which denotes the
      structural characterization of the molecules. Principal component analysis was
      performed to see the distribution of the compounds from two data sets for the
      constitutional descriptors. The distribution of compounds in score plot based on
      constitutional descriptors suggests unification of quinoxaline data sets which is
      useful for the model development. Outlier detection was performed from the
      standpoint of residual analysis of the partial least squares regression models.
      The superiority of the constitutional descriptors over other calculated molecular
      descriptors has been established from the standpoint of leave-one-out cross
      validation technique associated with partial least squares regression analysis.
      Internal validation through the leave-many-out methodology was also performed
      with good results, assuring the stability of the models. The results obtained
      from linear partial least squares regression analysis lead to a statistically
      significant and robust quantitative structure-activity relationship modeling.

PMID- 18637991
TI  - Aging Male Questionnaire in normal and complaining men.
AB  - INTRODUCTION: Detection of androgen deficiency is at least, based on specific
      questionnaires, defined by sexual, psychological, and somatic variables. Their
      relationships with sexual hormone levels are poorly understood. AIM: To assess
      the Aging Male Symptoms (AMS) score and sex hormone levels in normal and
      complaining men in order to define the relationship between the key parameters
      related to androgen deficiency. METHODS: Nine hundred and three men were
      interviewed via phone by a trained interviewer who completed the questionnaire;
      539 men consulting for a checkup in a health center and 471 complaining men, who
      completed the AMS scale in clinical setting, were selected, after excluding
      subjects with major and/or chronic diseases, endocrine disorders, psychological
      dysfunctions, and metabolic syndrome. MAIN OUTCOME MEASURES: Total AMS score and
      psychological, somatic and sexual subscores, as a function of age. RESULTS: The
      AMS questionnaires the were completed in a clinical setting or via calling-up
      line were comparable. In both cases, total AMS scores and subscores were
      significantly dependent of age and were correlated to income. In normal men, the
      only two parameters that significantly changed with age were the AMS sexual
      subscore and bioavailable testosterone (BT). Complaining men aged more than 50
      years old had a significantly higher total AMS scores, subscores, and BT level
      than normal men up to 60 years old, and these differences weakened with
      increasing age. In normal and complaining men, whatever the AMS sexual subscore,
      any variation in testosterone (T) and BT levels was observed. CONCLUSIONS: The
      AMS scale could be defined as a screening test for androgen deficiency symptoms
      in men between 50 and 65 years of age. The sexual AMS subscore and BT level are
      the key variables to identify those symptoms; the severity of sexual symptoms can
      not be explained by a BT level decrease.

PMID- 18637992
TI  - Male partners of women with provoked vestibulodynia: attributions for pain and
      their implications for dyadic adjustment, sexual satisfaction, and psychological
      distress.
AB  - INTRODUCTION: Provoked vestibulodynia is a female genital pain condition that
      results in sexual dysfunction and impacts negatively on the couple. Although
      patients' causal attributions have been linked to worse psychosexual outcomes, no
      study has documented the male partners' perspective of this distressing problem
      and its potential influence on their psychosexual adaptation. AIM: To identify
      whether male partners' attributions for vestibulodynia are possible predictors of
      their dyadic adjustment, sexual functioning, sexual satisfaction, and
      psychological distress, as well as of women's pain and sexual functioning.
      METHODS: Thirty-eight women with vestibulodynia first completed measures of pain
      intensity and sexual functioning. Male partners responded to mailed
      questionnaires assessing their own attributions for genital pain as well as their
      psychological distress, relationship adjustment, sexual functioning, and sexual
      satisfaction. MAIN OUTCOME MEASURES: Women completed the McGill-Melzack Pain
      Questionnaire (MPQ) and the Female Sexual Function Index (FSFI). Attributions of
      male partners were measured using an adapted version of the Attributional Style
      Questionnaire (ASQ)-Partner Version. Men also filled out the Brief Symptom
      Inventory (BSI), the Dyadic Adjustment Scale (DAS), the Sexual History Form
      (SHF), and the Global Measure of Sexual Satisfaction (GMSEX). RESULTS: All four
      negative attribution dimensions and higher levels of women's pain intensity
      successfully predicted increased psychological distress in male partners. Higher
      levels of both internal and global attributions were associated with men's poorer
      dyadic adjustment, whereas global and stable attributions were related to their
      lower sexual satisfaction. Attributions failed to significantly predict sexual
      functioning in male partners and women's pain and sexual functioning.
      CONCLUSIONS: Evaluation and treatment of sexual pain problems should involve both
      partners and should explore the role of negative attributions.

PMID- 18637993
TI  - Sacral neuromodulation for lower urinary tract dysfunction and impact on erectile
      function.
AB  - INTRODUCTION: The first sacral nerve stimulators were for urinary urgency
      incontinence, urgency-frequency, and nonobstructive urinary retention. Since
      then, observations have been made for benefits beyond voiding disorders. AIM: To
      evaluate if sacral neuromodulation (SNM) using the InterStim system (Medtronic
      Inc., Minneapolis, MN, USA) improves erectile function. METHODS: From January
      1999 to January 2007, 54 males, mean age 42.8, underwent a permanent SNM for
      lower urinary tract symptoms (LUTS). Pre-SNM only subjects with concomitant
      erectile impairment according to the five-item version of the International Index
      of Erectile Function (IIEF-5), with normal blood sexual hormonal status, and
      responding to an intracavernous injection test 10 microg were enrolled in our
      study. Three months after permanent implantation, the IIEF-5 was completed again.
      Those who benefited significantly in erectile function completed the IIEF-5
      semiannually. A final checkup was performed in July 2007. MAIN OUTCOME MEASURES:
      A score of IIEF-5 equal to or higher than 25% compared to baseline indicated
      remarkable clinical enhancement. RESULTS: Presurgery, two patients were excluded.
      Overall, 22 subjects (42.3%) showed erectile impairment (14 were neurogenic). In
      the first visit post-SNM, five retentionists of neurogenic origin and two with
      overactive bladder syndrome of idiopathic origin achieved noticeable erectile
      improvement. Their median IIEF-5 score shifted from 14.6 to 22.2, and 15.5 to
      22.5, respectively. During follow-up, two neurogenics lost the benefits
      concerning voiding and erection and recovered them after a new implant in the
      contralateral sacral S3 root. In the final visit, the seven responders reached an
      IIEF-5 score of at least 22. CONCLUSIONS: Our study showed a clinically important
      benefit of sexual function mainly for neurogenic retentionists. Future research
      should test SNM in a larger sample of subjects, exclusively with sexual
      dysfunctions, in order to better understand the mechanism of action of SNM on
      erectile function.

PMID- 18637994
TI  - Genetic factors increase fecundity in female maternal relatives of bisexual men
      as in homosexuals.
AB  - INTRODUCTION: Recent studies on male homosexuals showed increased fecundity of
      maternal female relatives of homosexual probands, compared to those of
      heterosexual controls. We have suggested that these data could be explained by
      the transmission, in the maternal line, of an X-linked genetic factor that
      promotes androphilic behavior in females and homosexuality in males. AIM: Our
      original studies were on relatives of male subjects who declared themselves to be
      exclusively homosexual. However, the relationship between homosexuality and
      bisexuality, including the possibility of shared genetic factors, is complex and
      largely unexplored. To cast light on this issue, in the present study we examined
      whether relatives of bisexuals show the same indirect fitness advantage as
      previously demonstrated for homosexuals. MAIN OUTCOME MEASURES: Subjects
      completed a questionnaire on their sexual orientation, sexual behavior, and their
      own and their relatives' fecundity. METHODS: We studied 239 male subjects,
      comprising 88 who were exclusively or almost exclusively heterosexual (pooled to
      comprise our "heterosexual" group), 86 who were bisexual, and 65 exclusively or
      almost exclusively homosexual individuals (pooled in our "homosexual" group).
      Bisexuals were here defined on the basis of self-identification, lifetime sexual
      behavior, marital status, and fecundity. RESULTS: We show that fecundity of
      female relatives of the maternal line does not differ between bisexuals and
      homosexuals. As in the previous study on homosexuals, mothers of bisexuals show
      significantly higher fecundity, as do females in the maternal line (cumulated
      fecundity of mothers, maternal grandparents, and maternal aunts), compared to the
      corresponding relatives of heterosexual controls.This study also shows that both
      bisexuals and homosexuals were more frequently second and third born. However,
      only homosexuals had an excess of older male siblings, compared to heterosexuals.
      CONCLUSIONS: We present evidence of an X-chromosomal genetic factor that is
      associated with bisexuality in men and promotes fecundity in female carriers.

PMID- 18637995
TI  - A woman's history of vaginal orgasm is discernible from her walk.
AB  - INTRODUCTION: Research has demonstrated the association between vaginal orgasm
      and better mental health. Some theories of psychotherapy assert a link between
      muscle blocks and disturbances of both character and sexual function. In
      Functional-Sexological therapy, one focus of treatment is amelioration of
      voluntary movement. The present study examines the association of general
      everyday body movement with history of vaginal orgasm. AIM: The objective was to
      determine if appropriately trained sexologists could infer women's history of
      vaginal orgasm from observing only their gait. METHODS: Women with known
      histories of either vaginal orgasm or vaginal anorgasmia were videotaped walking
      on the street, and their orgasmic status was judged by sexologists blind to their
      history. MAIN OUTCOME MEASURE: The concordance between having had orgasms
      triggered by penile-vaginal intercourse (not orgasm from direct clitoral
      stimulation) and raters' inferences of vaginal orgasm history based on
      observation of the woman's walk was the main outcome measure. RESULTS: In the
      sample of healthy young Belgian women (half of whom were vaginally orgasmic),
      history of vaginal orgasm (triggered solely by penile-vaginal intercourse) was
      diagnosable at far better than chance level (81.25% correct, Fisher's Exact Test
      P < 0.05) by appropriately trained sexologists. Clitoral orgasm history was
      unrelated to both ratings and to vaginal orgasm history. Exploratory analyses
      suggest that greater pelvic and vertebral rotation and stride length might be
      characteristic of the gait of women who have experienced vaginal orgasm (r =
      0.51, P < 0.05). CONCLUSIONS: The discerning observer may infer women's
      experience of vaginal orgasm from a gait that comprises fluidity, energy,
      sensuality, freedom, and absence of both flaccid and locked muscles. Results are
      discussed with regard to previous research on gait, the effect of the musculature
      on sexual function, the special nature of vaginal orgasm, and implications for
      sexual therapy.

PMID- 18637996
TI  - Surgical correction of Peyronie's disease via tunica albuginea plication or
      partial plaque excision with pericardial graft: long-term follow up.
AB  - INTRODUCTION: Limited publications exist regarding long-term outcomes of surgical
      correction for Peyronie's Disease (PD). AIM: To report on long-term postoperative
      parameters including rigidity, curvature, length, sensation, function, and
      patient satisfaction in men with PD treated surgically via Tunica Albuginea
      Plication (TAP) or Partial Plaque Excision with Tutoplast Human Pericardial
      Grafting (PEG). MAIN OUTCOME MEASURES: Objective and subjective data regarding
      patients who underwent either TAP or PEG. METHODS: We report on 142 patients (61
      TAP and 81 PEG) with both objective data and subjective patient reports on their
      postoperative experience. Patients underwent either TAP or PEG following our
      previously published algorithm. Data was collected via chart review and an
      internally generated survey, in which patients were asked about their rigidity,
      straightness, penile length, sensation, sexual function and satisfaction.
      RESULTS: Average follow up for TAP patients was 72 months (range 8-147) and 58
      months (range 6-185) for PEG patients. At survey time, 93% of TAP and 91% of PEG
      patients reported curvatures of less than 30o. Rigidity was reportedly as good as
      or better than preoperative in 81% of TAP and 68% of PEG patients, and was
      adequate for coitus in 90% of TAP and 79% of PEG patients with or without the use
      of PDE5i. Objective flaccid stretched penile length measurements obtained pre and
      postoperatively show an average overall length gain of 0.6 cm (range -3.5-3.5)
      for TAP and 0.2 cm (range -1.5-2.0) for PEG patients. Sensation was reportedly as
      good as or better than preoperative in 69% of both TAP and PEG patients; 98% of
      TAP patients and 90% of PEG are able to achieve orgasm. 82% of TAP patients and
      75% of PEG patients were either very satisfied or satisfied. CONCLUSION: Our long
      term results support both TAP and PEG as durable surgical therapy for men with
      clinically significant PD.

PMID- 18637997
TI  - Sildenafil and a compound stimulating endothelial NO synthase modify sexual
      incentive motivation and copulatory behavior in male Wistar and Fisher 344 rats.
AB  - INTRODUCTION: Earlier studies have shown that sildenafil may modify some aspects
      of male rat sexual behavior and sexual incentive motivation. Stimulation of
      endothelial nitric oxide synthase (eNOS) has also been reported to affect sexual
      motivation in old rats. AIM: To determine the effects of sildenafil and a
      compound stimulating eNOS on copulatory behavior and sexual incentive motivation
      in young adult Fisher 344 and Wistar male rats. METHODS: The rats were selected
      for a low intromission ratio, and then treated with Impaza (stimulator of eNOS),
      sildenafil, or Impaza + sildenafil for 28 days. Tests for copulatory behavior and
      sexual incentive motivation were performed before the beginning of treatment and
      at days 7, 14, and 28 of treatment. MAIN OUTCOME MEASURES: Standard parameters of
      copulatory behavior and sexual incentive motivation. Measurements of penis length
      at mount, intromission, and ejaculation. RESULTS: The Fisher 344 rats displayed a
      higher level of sexual incentive motivation than the Wistar rats, while the
      copulatory behavior was similar in both strains. Impaza and sildenafil enhanced
      the sexual incentive motivation after 28 days of treatment in the Wistar rats,
      but failed to do so in the Fisher 344 rats. The copulatory behavior was
      unaffected in the Wistar strain, while the Fisher 344 males had an enhanced
      intromission ratio after treatment with Impaza and sildenafil for 28 days.
      CONCLUSIONS: The nitric oxide-guanylyl cyclase pathway seems to be of importance
      for sexual incentive motivation in animals with a modest baseline level. The
      different drug effects in the Wistar and Fisher 344 rats can be attributed to
      baseline differences. The importance of eNOS for sexual functions should not be
      overlooked.

PMID- 18637998
TI  - A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal
      tissues of hypercholesterolemic rabbits.
AB  - INTRODUCTION: Hypercholesterolemia causes a decrease in normal corporal tissue
      vasoreactivity in a preclinical model of erectile dysfunction. Previous studies
      have shown that intracorporal injection (ICI) of basic fibroblast growth factor
      (bFGF) reverses some of the detrimental vasoreactivity effects of
      hypercholesterolemia and increases vascular endothelial growth factor (VEGF)
      expression. AIM: We sought to determine whether the beneficial effects of bFGF
      are VEGF-mediated. METHODS: A total of 32 New Zealand white rabbits were fed a 1%
      cholesterol diet for 6 weeks and randomly divided into four groups (N = 8/group).
      Group 1 received a 2.5 microg bFGF ICI and 2.5 x 10(11) viral particle unit (vpu)
      of adenovirus encoding beta-galactosidase (Ad beta-gal) ICI, 10 days later. Group
      2 received a 2.5 microg bFGF ICI and 2.5 x 10(11) vpu of adenovirus encoding
      soluble VEGF receptor (VEGFR) (AdsVEGFR, a VEGF trap) ICI, 10 days later. Group 3
      received phosphate buffered saline solution (PBS) ICI and 2.5 x 10(11) vpu Ad
      beta-gal ICI, 10 days later. Group 4 received PBS ICI and 2.5 x 10(11) vpu
      AdsVEGFR ICI, 10 days later. MAIN OUTCOME MEASURES: The corpus cavernosum was
      harvested for vasoreactivity studies 10 days post viral injection. The effective
      dose of 50% maximum relaxation was determined. VEGF levels were assessed by
      enzyme-linked immunosorbent assay. Total and phosphorylated Akt and endothelial
      nitric oxide were analyzed by Western blot. RESULTS: Endothelium-dependent
      vasoreactivity was significantly greater in Group 1 vs. all other groups. The
      VEGF trap eliminated the beneficial effects of bFGF on endothelium-dependent
      vasoreactivity and decreased Akt and nitric oxide phosphorylation. CONCLUSIONS:
      These data demonstrate that VEGF activity contributes much of the therapeutic
      modulation of bFGF-mediated vasoreactivity in corporal tissue.

PMID- 18637999
TI  - Sexual counseling in elderly couples.
AB  - INTRODUCTION: Sexual health of the elderly has long been either a taboo or a non
      medical life style luxury issue. Increasing longevity of women and men,
      reconceptualization of sexual health as part of general health, and the
      development of drugs aiming at improvement of sexual function have contributed to
      a change in the attitude of the elderly and the medical community, thus
      increasing the demands for help. AIMS: To respond to these demands, caregivers
      need to be informed about the statistics concerning the sex life of the elderly,
      need to understand the biological, psychological, interaction and social factors
      that determine the sexual health of the aging population, need a comprehensive
      diagnostic and therapeutic approach, taking into account the specific
      characteristics of the aging male, female, and the couple. MAIN OUTCOME MEASURES:
      Diagnostic and therapeutic algorithm integrating the biopsychosocial profile of
      the aging male and female and the interaction characteristics of the couple.
      METHODS: Review of the literature, analysis of cases, and review of
      multidisciplinary case discussions of elderly couples with sexual problems
      consulting the Division of Sexual Medicine at the University Hospital of Basel.
      RESULTS: Sexual dysfunction is highly prevalent in the aging population, with
      hypoactive sexual desire disorder and pain disorders being the most frequent in
      women, and premature ejaculation and erectile dysfunction being the most frequent
      in men. The specific characteristics of the sexual ill health in elderly couples
      are the interactions of physical and mental morbidity including therapies,
      multidimensional sexual dysfunctions in both partners, dyssynchrony in personal
      development and sexual scripts, and a longstanding fixed interactional pattern
      with rigid "sexual roles." The diagnostic approach has to integrate sexological
      descriptive diagnoses of both partners, their biopsychosocial profile, and the
      couple's history and interactional pattern. From this diagnostic framework,
      caregivers must design specific, multidisciplinary therapeutic strategies for the
      elderly couple, which include biomedical, individual psychotherapeutic, and
      systemic interventions in various combinations. CONCLUSION: The increasing demand
      for help of elderly couples with sexual dysfunction requires a multidisciplinary
      approach in diagnosis and therapy combining the knowledge and skills of
      urologists, gynecologists, internists, and various mental health professionals to
      provide individualized age-related care.

PMID- 18638000
TI  - Androgen replacement in men undergoing treatment for prostate cancer.
AB  - INTRODUCTION: Hypogonadism is a clinical and biochemical syndrome that may cause
      significant detriment in the quality of life and adversely affect the function of
      multiple organ systems. With the increase in life expectancy and prostate cancer
      (PCa) survival, a significant increase in the number of men with hypogonadism who
      have undergone presumably curative treatment for PCa is anticipated. AIM: To
      critically review the literature regarding testosterone replacement therapy (TRT)
      after PCa treatment with curative intent. MAIN OUTCOME MEASURES: Review of peer
      reviewed literature. There was special focus on the potential implications and
      safety of TRT in men with hypogonadism who have undergone curative treatment for
      PCa. METHODS: English-language relevant publications were identified via
      electronic medical databases (MEDLINE, EMBASE, and DARE). RESULTS: Despite the
      wide spread of contraindication of testosterone replacement in men with known or
      suspected PCa, there is no convincing evidence that the normalization of
      testosterone serum levels in men with low but no castrate levels is deleterious.
      In the few available case series describing testosterone replacement after
      treatment for PCa, no case of clinical or biochemical progression was observed.
      CONCLUSIONS: Although further studies are necessary before definitive conclusions
      can be drawn, the available evidence suggests that TRT can be cautiously
      considered in selected hypogonadal men treated with curative intent for PCa and
      without evidence of active disease.

PMID- 18638001
TI  - Risk factors for emotional and relationship problems in Peyronie's disease.
AB  - INTRODUCTION: Peyronie's disease (PD) occurs in 3-9% of all men. Little is known
      regarding the specific psychological or emotional disruptions to sexuality
      associated with PD. AIM: Our primary aim was to identify risk factors associated
      with psychosocial difficulties in men with PD. METHODS: This cross-sectional
      study enrolled patients from a single clinical practice. Detailed medical
      histories, physical examinations, and a PD-specific questionnaire were used to
      define clinical characteristics. Odds ratios (ORs) were used as a measure of
      association. MAIN OUTCOME MEASURES: Emotional and relationship problems were
      determined by "yes" or "no" answers to two specific questions. RESULTS: The mean
      age of all PD patients (N = 245) was 54.4 years (range 19.4-75.6); 62% were
      married, and 59% presented within 2 years of disease onset. The overall
      prevalence of emotional and relationship problems attributable to PD was 81% and
      54%, respectively. Among men who had relationship problems, the prevalence of
      emotional problems was 93%. In men with emotional problems due to PD,
      relationship issues were observed in 62%. Multivariable analysis revealed that
      emotional difficulties (OR 6.9, P < 0.001) and ability to have intercourse (OR
      0.4, P = 0.004) were independently associated with relationship problems.
      Relationship problems (OR 8.0, P < 0.001) and loss of penile length (OR 2.7, P =
      0.02) were significant independent predictors of emotional problems after
      adjustment for the ability to maintain erections, low libido, and penile pain.
      CONCLUSIONS: Among men with PD, there is a very high prevalence of emotional and
      relationship problems. Loss of penile length and inability to have intercourse
      are strong predictors of these problems and as such make ideal targets for
      intervention. Medical and surgical therapies may enhance quality of life through
      their ability to improve sexual function. Further research will characterize the
      ways in which individual symptoms affect emotional and psychological well-being.

PMID- 18638002
TI  - Systemic vascular endothelial dysfunction in Peyronie's disease.
AB  - INTRODUCTION: Many patients with Peyronie's disease (PD) have one or more risk
      factors (RFs) for atherosclerosis and endothelial dysfunction. It is well
      recognized that such RFs commonly lead to the development of systemic vascular
      abnormalities. While not necessarily so, this may implicate vascular dysfunction
      in its pathogenesis. The cause of PD remains obscure despite intense research
      over the years and investigating the role of vascular dysfunction in the
      pathogenesis of PD is a novel approach worth undertaking. AIM: To test our
      hypothesis that PD is associated with systemic vascular changes even in the
      absence of RFs for atherosclerosis and endothelial dysfunction. METHODS: Vascular
      function was assessed using high-resolution brachial artery ultrasound in 23 PD
      patients (aged 30-65 years) without RFs for endothelial dysfunction and
      atherosclerosis, and 23 age-matched healthy controls. Endothelium-dependent, flow
      mediated brachial artery dilation was measured in response to increased shear
      stress (reactive hyperemia induced by 5 minutes of forearm ischemia). This
      response was contrasted with that of 400 microg sublingual glyceryl trinitrate,
      an endothelium-independent vasodilator. Anthropometric characteristics, blood
      pressure, fasting lipids, and glucose were also measured. MAIN OUTCOME MEASURE:
      Endothelium-dependent, flow-mediated brachial artery dilation and glyceryl
      trinitrate-induced endothelium-independent vasodilation. RESULTS: Endothelium
      dependent flow-mediated dilation (FMD) was impaired in PD patients compared to
      controls (5.62 +/- 0.58% vs. 7.46 +/- 0.56%, P = 0.03). In contrast, responses to
      glyceryl trinitrate were similar in PD patients and controls as were blood
      pressure, lipid, and glucose values. FMD remained impaired after multivariable
      adjustment for potential confounders. CONCLUSION: Patients with Peyronie's
      disease have evidence of systemic vascular changes in the way of systemic conduit
      artery endothelial impairment even in the absence of RFs for atherosclerosis and
      endothelial dysfunction. These wider vascular abnormalities in PD are likely to
      be of clinical relevance and require further study.

PMID- 18638003
TI  - The effect of Korean red ginseng extract on the relaxation response in isolated
      rabbit vaginal tissue and its mechanism.
AB  - INTRODUCTION: Ginseng is an herbal medicine with a variety of biological
      activities. AIM: The purpose of this study was to investigate the effect of
      Korean red ginseng (KRG) extract on the relaxation response in isolated rabbit
      vaginal tissue and its mechanism as a potential therapeutic agent for female
      sexual dysfunction. METHOD: Strips of rabbit vagina were mounted in organ
      chambers to measure isometric tension. After the strips were precontracted with
      phenylephrine, the contractile responses to KRG extract (1-20 mg/mL), nitric
      oxide inhibitor (N[omega]-nitro-L-arginine methyl ester [L-NAME]), an inhibitor
      of soluble guanylate cyclase (methylene blue), an inhibitor of Ca(2+)-activated
      K(+) channels (tetraethylammonium [TEA]), and an adenosine triphosphate (ATP)
      sensitive K(+) channel blocker (glybenclamide) were examined. MAIN OUTCOME
      MEASURES: The relaxation of the vaginal tissue strip was assessed after treating
      KRG extract or other chemicals. RESULTS: KRG (1-20 mg/mL) extract relaxed the
      vaginal tissue strip in a dose-dependent manner up to 85%. The relaxation effect
      was significantly inhibited by L-NAME (30 microM) and methylene blue (30 microM)
      (P < 0.05). In addition, KRG inhibited the contraction induced by depolarization
      with 10, 20, and 40 mM KCl. The KRG-induced relaxation effect was significantly
      inhibited by TEA (300 microM) (P < 0.05), and not by glybenclamide (30 microM).
      CONCLUSIONS: These data show that KRG extract has a relaxing effect on rabbit
      vaginal smooth muscle tissue. These effects might be mediated partly through the
      NO pathway and hyperpolarization via Ca(2+)-activated K(+) channels.

PMID- 18638004
TI  - Efficacy and safety of mirodenafil, a new oral phosphodiesterase type 5
      inhibitor, for treatment of erectile dysfunction.
AB  - INTRODUCTION: Mirodenafil is a newly developed oral phosphodiesterase type 5
      inhibitor, currently under investigation as a treatment for erectile dysfunction
      (ED). AIM: We investigated the efficacy and safety of on demand mirodenafil
      therapy at fixed doses (50 and 100 mg) in Korean men with a broad range of ED.
      METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel
      group, fixed-dose study was conducted with 223 subjects who were randomized to
      placebo or mirodenafil at fixed doses of 50 or 100 mg for 12 weeks on an "as
      needed" basis. MAIN OUTCOME MEASURES: Primary efficacy measures were scores on
      the International Index of Erectile Function (IIEF) Question 3 (Q3) and Question
      4 (Q4). Secondary efficacy measures included all domain scores of the IIEF,
      Sexual Encounter Profile Question 2 (SEP2), Sexual Encounter Profile Question 3
      (SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist
      (LSC). Safety assessments included laboratory tests, vital signs, physical
      examination, 12-lead electrocardiogram recordings, and patients' reporting of
      adverse events. RESULTS: Mirodenafil 50 and 100 mg groups showed a significantly
      greater increase in IIEF Q3 (P = 0.0001, P < 0.0001, respectively) and Q4 scores
      (both P < 0.0001) at the end point compared with the placebo group. And
      mirodenafil in both doses significantly improved the scores of all five domains
      of the IIEF, SEP2, and SEP3 as well as the percentages of patients responding
      positively to the GAQ compared with the placebo group. As for LSC scores, the two
      mirodenafil groups showed significantly greater improvements in items regarding
      life as a whole, sexual life, and partner relationship than the placebo group.
      Most treatment-associated adverse events were of mild intensity, resolving
      spontaneously. CONCLUSIONS: Mirodenafil, in doses of 50 or 100 mg, significantly
      improved erectile function and were well tolerated in a representative population
      of Korean men with broad-spectrum ED of various etiologies and severities.

PMID- 18638006
TI  - Comparative efficacy assessment of tamsulosin vs. tamsulosin plus tadalafil in
      the treatment of LUTS/BPH. Pilot study.
AB  - INTRODUCTION: The high incidence of erectile dysfunction (ED) and lower urinary
      tract symptoms (LUTS) in aging men and the same pathophysiology make probable to
      treat both disorders with the same treatment. Numerous authors evaluated the
      actions of PDE5i in improving the LUTS/(benign prostate hyperplasia) BPH. AIM: To
      assess the efficacy and safety of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day
      plus tadalafil 20 mg/day in patients with LUTS in a crossover design study. MAIN
      OUTCOMES MEASURES: International Prostate Symptoms Score (IPSS), IPSS Quality of
      Life (IPSS-QOL), maximum flow rate (Qmax), post-void residual volume (PVR),
      International Index of Erectile Function-Erectile Function Domain (IIEF-EF),
      Global Assessment Quality (GAQ). For the statistical analysis, a Tukey-Kramer
      multicomparison test was used. METHODS: A randomized, double-blind, crossover
      study was conducted from September 2007 to February 2008 in one center. Thirty
      men, older than 50 years old, with a history of LUTS/BPH of at least 6 months,
      were randomized into two groups to receive tamsulosin 0.4 mg/day vs. tamsulosin
      0.4 mg/day plus tadalafil 20 mg/day for 45 days, and then switched to the other
      treatment mode for other 45 days. RESULTS: Twenty-seven patients completed the
      study. Improvements of IPSS score and IPSS-QOL were significant with both
      treatments but greater with the drug combination. Both regimens similarly
      improved the Qmax and decreased the PVR volume from baseline (P < 0.001) with no
      significant differences between tamsulosin alone vs. tamsulosin and tadalafil (P
      > 0.05). The IIEF improved with tamsulosin plus tadalafil (P < 0.001) but not
      with tamsulosin alone (P > 0.05). The GAQ showed that all patients preferred the
      combination scheme. Both treatments were well tolerated. CONCLUSION; Tamsulosin
      0.4 mg/day plus tadalafil 20 mg/day was more effective than tamsulosin 0.4 mg/day
      alone to improve LUTS and erectile dysfunction and was also well tolerated. Large
      scale, randomized, placebo-controlled studies are needed to further assess the
      long-term safety and effectiveness of these agents in treating LUTS/BPH with or
      without ED.

PMID- 18638007
TI  - Perceived ejaculatory latency and pleasure in different outlets.
AB  - INTRODUCTION: Ejaculatory latencies have been studied in coitus and with
      masturbation, but not with oral or manual stimulation by a partner. AIM: The
      present study extended research on ejaculatory latency to these outlets, and
      investigated the effect of perceived pleasure on self-reported ejaculatory
      latency. METHOD: A convenience sample of male college students, not selected for
      sexual dysfunction, completed questionnaires assessing the outcome measures. MAIN
      OUTCOME MEASURES: Self-report measures of latency to ejaculation in, and
      perceived pleasure associated with, four different outlets (vaginal intercourse,
      oral intercourse, manual stimulation by a partner, and masturbation). RESULTS:
      Ejaculatory latencies in partnered activities were predictive of each other.
      Masturbatory latencies were predictive of coital latencies but not oral or manual
      stimulation latencies; all the partnered activities were predictive of each
      other. There was no difference in time to ejaculation among any of the partnered
      outlets, although ejaculation occurred more quickly with masturbation than with
      coitus or manual stimulation. In terms of pleasure associated with the outlets,
      vaginal and oral intercourse were perceived as equally pleasurable, and both were
      rated as more pleasurable than manual stimulation or masturbation, which did not
      differ from each other. CONCLUSIONS: These results suggest that rapidity of
      ejaculation is consistent across outlets for the partnered sexual activities, and
      that there is little unique-in terms of ejaculatory latency--about vaginal
      intercourse compared with oral or manual stimulation by a partner. Masturbation,
      however, does differ from the partnered activities. Although the average
      correlation, for individuals, between latency and pleasure for the different
      outlets is near zero, there are subgroups of men who have (i) a negative
      relation, (ii) a positive relation, or (iii) no relation. Results show that men,
      for whom greater pleasure is associated with shorter latency, are more likely to
      be dissatisfied with their intravaginal ejaculatory latencies, regardless of
      actual latency.

PMID- 18638008
TI  - Sexual function, dysfunction, and sexual distress in a prospective, population
      based sample of mid-aged, Australian-born women.
AB  - INTRODUCTION: Previous, population-based studies investigating the risk factors
      for sexual distress have not drawn on longitudinal data. AIMS: Determine the
      prevalence of sexual distress and dysfunction, explore factors associated
      with/predictive of sexual distress, and describe changes in sexual function over
      a decade in a population-based sample of mid-aged women. METHODS: Eleven-year
      prospective study of Australian-born women, aged 45-55 years, and menstruating at
      baseline. Short Personal Experiences Questionnaire (SPEQ) was completed in years
      1 to 8 and 11 of follow-up. Female Sexual Distress Scale (FSDS) was completed in
      the 11th year of follow-up. MAIN OUTCOME MEASURES: Validated outcome measures
      were the SPEQ (total sex score <or=7 indicates low sexual function) and FSDS
      (score >or=15 indicates sexual distress). RESULTS: Two hundred fifty-seven women
      were interviewed in the 11th year of follow-up. All domains of sexual function
      declined significantly in the decade studied. Women using hormone therapy in year
      11 had significantly greater responsivity and higher frequency of sexual
      activities than nonusers. Two hundred four women completed both the FSDS and SPEQ
      questionnaires. One hundred sixty-six (81%) women had an SPEQ score <or=7 of whom
      34 (17% of the total sample) had an FSDS score >or=15, and were classified as
      having female sexual dysfunction. The multiple logistic regression analysis found
      that female sexual distress was concurrently associated with higher depression
      scores (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.10, 1.56) and more
      negative feelings for partner (OR 0.49, 95% CI 0.32, 0.76) and predicted by prior
      negative feelings for partner (OR 0.31, 95% CI 0.14, 0.70), and a greater decline
      in total sex score (OR 0.77, 95% CI 0.59, 0.99). CONCLUSIONS: By the end of the
      sixth decade, women have low levels of sexual function. Hormone therapy may help
      these women maintain sexual function. A minority of these mostly postmenopausal
      women are significantly distressed about low sexual function. Sexual distress is
      associated with depression and relationship factors.

PMID- 18638009
TI  - Is sexual dysfunction in women with obstructive sleep apnea-hypopnea syndrome
      associated with the severity of the disease? A pilot study.
AB  - INTRODUCTION: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may have a
      significant negative effect on sexual function. AIM: To evaluate female sexual
      function in women with OSAHS. METHODS: Twenty-six patients with OSAHS were
      evaluated in two groups according to apnea-hypopnea index as mild (5-15, Group I,
      N = 16) or moderate-severe (>or=15, Group II, N = 10). A third group (N = 10) of
      patients suspected of sleeping disorders other than OSAHS who also underwent
      polysomnographic studies served as the control group. All women were evaluated
      with a detailed sexual history including Female Sexual Function Index (FSFI)
      questionnaire and Beck Depression Inventory (BDI). Meanwhile, serum levels of
      estradiol, prolactin, total and free testosterone and dihydroepiandrostenedione-S
      were determined. MAIN OUTCOME MEASURES: FSFI, BDI, and serum hormonal levels.
      RESULTS: The mean ages and total FSFI scores of Group I, Group II and the control
      group were 46 +/- 7.1, 45 +/- 3.8, and 41 +/- 5.4 (P > 0.05); 24.7 +/- 5.3, 24.5
      +/- 6.3, and 30.0 +/- 2.5 (P < 0.05), respectively. The mean FSFI domain scores
      were not statistically different between Groups I and II (P > 0.05) (desire, 3.18
      +/- 1.2 vs. 2.92 +/- 1.6; arousal, 3.96 +/- 1.1 vs. 3.67 +/- 1.2; lubrication,
      4.83 +/- 1.0 vs. 4.12 +/- 1.1; orgasm 4.0 +/- 1.1 vs. 5.15 +/- 2.9; satisfaction
      3.96 +/- 1.1 vs. 4.05 +/- 1.4 pain; 4.84 +/- 1.2 vs. 4.65 +/- 1.3). However, the
      mean scores of desire (3.18 +/- 1.2 vs. 3.96 +/- 0.7), orgasm (4.0 +/- 1.1 vs.
      5.0 +/- 1.1), and satisfaction (3.96 +/- 1.1 vs. 4.76 +/- 1.0) domains of Group I
      were significantly lower than the control group. Meanwhile, the mean scores of
      desire (2.92 +/- 1.6 vs. 3.96 +/- 0.7) and lubrication (4.12 +/- 1.1 vs. 5.22 +/-
      0.9) domains were statistically different between Group II and the control group.
      The mean BDI scores of patients in Group I, Group II and the control group were
      19.3 +/- 6.3, 20.2 +/- 6.6, and 11.0 +/- 7.1, respectively (P < 0.01). In
      addition, the mean levels of hormonal parameters were not significantly different
      from the control group (P > 0.05). CONCLUSIONS: OSAHS is associated with a
      significant decrease in female sexual function. However, severity of OSAHS is not
      related with the degree of female sexual dysfunction (FSD). This situation
      reveals that both organic and psychogenic issues are being involved in FSD
      related with OSAHS.

PMID- 18638010
TI  - Absence of the JAK2 V617F mutation in patients with arterial thrombosis without
      overt myeloproliferative disease.

PMID- 18638011
TI  - Perioperative anticoagulation in patients having implantation of a cardiac
      pacemaker or defibrillator: a systematic review and practical management guide.
AB  - BACKGROUND: The perioperative management of anticoagulation in patients who are
      having implantation of a pacemaker or implantable cardioverter defibrillator
      (ICD) is a common clinical problem in which best clinical practise is not
      established. METHODS: We performed a systematic review of the literature to
      assess the safety (pocket hematoma risk) and efficacy (thromboembolism risk) of
      different management strategies. We included studies involving patients who were
      having pacemaker or ICD implantation whenever a portion of these patients were
      receiving a coumarin and also assessed pocket hematoma or thromboembolism.
      RESULTS: We identified eight studies that assessed two strategies used for
      perioperative anticoagulation management: interruption of a coumarin and use of
      bridging anticoagulation with a short-acting heparin; and perioperative
      continuation of a coumarin. A strategy involving bridging anticoagulation with
      therapeutic-dose heparin was associated with an incidence of pocket hematoma of
      12-20%. A strategy involving perioperative continuation of a coumarin was
      associated with an incidence of pocket bleeding of 1.9-6.6%. The incidence of
      thromboembolic events was 0-1%, irrespective of the perioperative anticoagulation
      strategy used. CONCLUSION: The perioperative anticoagulation management of
      patients who require pacemaker or ICD implantation is not established but a
      strategy involving postoperative bridging with intravenous heparin confers a high
      risk for bleeding whereas perioperative continuation of a coumarin appears to
      confer a lower risk for bleeding.

PMID- 18638012
TI  - Real-time risk stratification of patients with acute pulmonary embolism by
      grading the reflux of contrast into the inferior vena cava on computerized
      tomographic pulmonary angiography.
AB  - OBJECTIVE: To investigate whether fast grading of reflux of contrast to the
      inferior vena cava (IVC) on computerized tomographic pulmonary angiography (CTPA)
      is a potential biomarker for real-time risk stratification. METHODS: We
      retrospectively identified 343 patients investigated for possible pulmonary
      embolism (PE) by CTPA at our medical center between September 2004 and March
      2006. A total of 145 consecutive patients with PE (age 67 +/- 19 years) and 168
      consecutive ones with negative CTPAs (age 64 +/- 20 years) fulfilled entry
      criteria. CTPAs were evaluated for retrograde reflux of contrast to the IVC by
      fast visual grading from 1 to 6 using the original axial images. Pulmonary
      obstruction index, the diameters of right and left ventricles and pulmonary
      artery, and patient survival data were recorded as well. RESULTS: Twenty-nine
      (20.0%) patients with positive CTs and 23 (13.7%) patients with negative CTs had
      substantial degrees (>or=4) of reflux of contrast to the IVC (P = 0.14). The
      Kaplan-Meier 30-day survival curves demonstrated significant reduction in
      survival in individuals with PE and grade >or=4 reflux of contrast to the IVC
      compared with lower grades (P = 0.008), but not in patients with grade >or=4 and
      no PE on CTPA (P = 0.26). The other cardiovascular parameters showed no
      significant correlation with survival in patients with and without PE.
      CONCLUSION: Substantial grades of reflux of contrast to the IVC during CTPA could
      predict early mortality in patients with acute PE. Rapid grading of reflux of
      contrast from the original axial CTPA images can be used for real-time risk
      stratification in patients with acute PE.

PMID- 18638013
TI  - A continuous 13C methacetin breath test for noninvasive assessment of
      intrahepatic inflammation and fibrosis in patients with chronic HCV infection and
      normal ALT.
AB  - SUMMARY: Up to 30% of patients with hepatitis C virus (HCV) infection and normal
      serum alanine aminotransferase (NALT) have significant liver disease. Currently,
      many of these patients undergo a liver biopsy to guide therapeutic decisions. The
      BreathID continuous online (13)C-methacetin breath test (MBT) reflects hepatic
      microsomal function and correlates with hepatic fibrosis. To assess its role in
      identifying intrahepatic inflammation and fibrosis in NALT patients, we tested
      100 patients with untreated chronic HCV infection, and 100 age- and sex-matched
      healthy volunteers using (13)C MBT following ingestion of 75 mg methacetin. All
      HCV patients had undergone a liver biopsy within 12 months of performing the MBT.
      Patients with a necroinflammatory grade <or=4 or >4, based on Ishak (modified
      HAI) score, HAIa + HAIb + HAIc + HAId, were defined as having low or high
      inflammation, respectively. Patients with a histological activity fibrosis stage
      <or=2 or >2, were defined as having nonsignificant or significant fibrosis,
      respectively. A proprietary algorithm to differentiate intrahepatic inflammation
      within chronic HCV patients with NALT achieved an area under the curve (AUC) of
      0.90. Setting a threshold on the point of best agreement (at 83%) results in 82%
      sensitivity and 84% specificity. With application of another proprietary
      algorithm to differentiate patients with nonsignificant or significant fibrosis,
      67% of liver biopsies performed in the patient group could have been avoided.
      This algorithm achieved an AUC of 0.92, with a sensitivity of 91% and a
      specificity of 88%. There was no correlation between body mass index (BMI) and
      MBT scores for patients with the same histological score. The continuous
      BreathID(13)C MBT is an accurate tool for measuring the degree of inflammation
      and fibrosis in patients with chronic HCV infection and NALT. As such, it may
      prove to be a powerful, noninvasive alternative to liver biopsy in the management
      of this patient population.

PMID- 18638014
TI  - Bacteremia in equine neonatal diarrhea: a retrospective study (1990-2007).
AB  - BACKGROUND: Bacteremia in sick foals is associated with survival, but the
      association of bacteremia and diarrhea is not reported. HYPOTHESIS: Neonatal
      foals with diarrhea will commonly be bacteremic. ANIMALS: One hundred and thirty
      three neonatal foals. METHODS: Records of all foals <30 days of age presenting
      with diarrhea between January 1990 and September 2007 were reviewed. RESULTS:
      Sixty-six of 133 foals (50%) were bacteremic at admission, with 75 isolates from
      the 66 samples. The blood culture from a further 18 foals (13.5%) grew coryneform
      bacteria. Nine foals (6.8%) had 2 or more organisms grown on blood culture. One
      foal had 5 different organisms, interpreted as contamination. Forty-eight foals
      (36%) had no growth on admission blood cultures. No cultures isolated fungal
      organisms. Excluding coryneform bacteria, 43 isolates (57%) were Gram-negative
      organisms and 32 isolates (43%) were Gram-positive organisms. The most common
      isolate was Enterococcus spp. (22 isolates, 29%), followed by Pantoea agglomerans
      (13 isolates, 17%). IgG concentration at admission was not associated with blood
      culture status. Blood culture status was not associated with survival to hospital
      discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Bacteremia is common in neonatal
      foals with diarrhea. Decisions regarding antimicrobial selection should be made
      with these differences in mind.

PMID- 18638015
TI  - Investigating TrkA expression in canine appendicular osteosarcoma.
AB  - BACKGROUND: The tropomyosin-related kinase A (TrkA) proto-oncogene encodes for a
      receptor that binds with high affinity to the neurotrophin ligand, nerve growth
      factor (NGF). Intracellular signaling mediated by the TrkA/NGF axis orchestrates
      neuronal cell differentiation, mitogenesis, and survival. Interestingly, TrkA
      also is expressed by bone forming cells, and its signaling promotes antiapoptotic
      effects in actively dividing osteoblasts. HYPOTHESIS: In canine immortalized cell
      lines and naturally occurring tumor samples, osteosarcoma (OSA) cells will
      express TrkA. In canine OSA cell lines, TrkA signaling will promote cell
      mitogenesis and survival. METHODS: In vitro, TrkA expression in canine OSA cell
      lines was assessed by reverse transcriptase-polymerase chain reaction, flow
      cytometry, and immunocytochemistry. In vitro, the involvement of TrkA-mediated
      signaling for cell mitogenesis and survival were investigated with commercially
      available assays. In vivo, TrkA expression was evaluated in primary tumors and
      pulmonary metastases with immunocytochemistry and immunohistochemistry,
      respectively. RESULTS: In vitro, canine OSA cells expressed TrkA mRNA and
      protein. Ligation of TrkA with exogenous NGF did not induce mitogenesis. Blockade
      of TrkA signaling with either a protein kinase inhibitor or NGF-neutralizing
      antibody induced apoptosis of canine OSA cell lines. In vivo, the majority
      (10/15) of canine OSA primary tumors and pulmonary metastases (9/12) expressed
      TrkA protein. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine OSA cells express TrkA,
      and its signaling protects against apoptosis. Most dogs with spontaneously
      arising OSA express TrkA within their primary tumors and pulmonary metastatic
      lesions, warranting further investigations with TrkA antagonists as a novel
      treatment option for canine OSA.

PMID- 18638016
TI  - Effect of pimobendan or benazepril hydrochloride on survival times in dogs with
      congestive heart failure caused by naturally occurring myxomatous mitral valve
      disease: the QUEST study.
AB  - BACKGROUND: Myxomatous mitral valve disease (MMVD) continues to be an important
      cause of morbidity and mortality in geriatric dogs despite conventional therapy.
      HYPOTHESIS: Pimobendan in addition to conventional therapy will extend time to
      sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when
      compared with conventional therapy plus benazepril in dogs with congestive heart
      failure (CHF) attributable to MMVD. ANIMALS: Two hundred and sixty client-owned
      dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and
      Australia. METHODS: A prospective single-blinded study with dogs randomized to PO
      receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0
      mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for
      heart failure, or treatment failure. RESULTS: Eight dogs were excluded from
      analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128
      to benazepril. One hundred and ninety dogs reached the primary endpoint; the
      median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard
      ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of
      pimobendan persisted after adjusting for all baseline variables. A longer time to
      reach the endpoint was also associated with being a Cavalier King Charles
      Spaniel, requiring a lower furosemide dose, and having a higher creatinine
      concentration. Increases in several indicators of cardiac enlargement (left
      atrial to aortic root ratio, vertebral heart scale, and percentage increase in
      left ventricular internal diameter in systole) were associated with a shorter
      time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Pimobendan plus conventional therapy prolongs time to sudden death,
      euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by
      MMVD compared with benazepril plus conventional therapy.

PMID- 18638017
TI  - Effect of sample quality on the sensitivity of endoscopic biopsy for detecting
      gastric and duodenal lesions in dogs and cats.
AB  - BACKGROUND: The quality of histopathology slides of endoscopic biopsies from
      different laboratories varies, but the effect of biopsy quality on outcome is
      unknown. HYPOTHESIS: The ability to demonstrate a histologic lesion in the
      stomach or duodenum of a dog or cat is affected by the quality of endoscopic
      biopsy samples submitted. More endoscopic samples are needed to find a lesion in
      poor-quality tissue specimens. ANIMALS: Tissues from 99 dogs and 51 cats were
      examined as clinical cases at 8 veterinary institutions or practices in 5
      countries. METHODS: Histopathology slides from sequential cases that underwent
      endoscopic biopsy were submitted by participating institutions. Quality of the
      histologic section of tissue (inadequate, marginal, adequate), type of lesion
      (lymphangiectasia, crypt lesion, villus blunting, cellular infiltrate), and
      severity of lesion (normal, mild, moderate, severe) were determined. Sensitivity
      of different quality tissue samples for finding different lesions was determined.
      RESULTS: Fewer samples were required from dogs for diagnosis as the quality of
      the sample improved from inadequate to marginal to adequate. Duodenal lesions in
      cats displayed the same trend except for moderate duodenal infiltrates for which
      quality of tissue sample made no difference. Gastric lesions in dogs and mild
      gastric lesions in cats had the same trend, whereas the number of tissue samples
      needed to diagnose moderately severe gastric lesions in cats was not affected by
      the quality of tissue sample. CONCLUSIONS AND CLINICAL IMPORTANCE: The quality of
      endoscopically obtained tissue samples has a profound effect on their sensitivity
      for identifying certain lesions, and there are differences between biopsies of
      canine and feline tissues.

PMID- 18638018
TI  - Comparison of the Accu-Chek Aviva point-of-care glucometer with blood gas and
      laboratory methods of analysis of glucose measurement in equine emergency
      patients.
AB  - BACKGROUND: More information is needed regarding accuracy of commonly used
      methods of glucose measurement in the critically ill horse. HYPOTHESIS:
      Glucometry will have good agreement with a laboratory standard. Glucometry with
      plasma will have better agreement than when performed with whole blood. ANIMALS:
      Fifty sequentially admitted equine emergency patients, aged >1year. METHODS:
      Venous blood was collected at admission and immediately analyzed by point-of-care
      glucometry on both whole blood (POC/WB) and plasma (POC/PL), a multielectrode
      blood gas analyzer with whole blood (BLG), and a standard laboratory method with
      plasma (CHEM). Paired data were compared using Lin's concordance correlation,
      Pearson's correlation, and robust regression. Bias and limits of agreement were
      tested by the Bland-Altman technique. Bivariate regression analysis was used to
      explore confounding factors. RESULTS: Concordance was significant for all
      comparisons, and was strongest for CHEM-POC/PL (0.977) and weakest for POC/WB
      POC/PL (0.668). Pearson's correlation was excellent for all comparisons except
      those with POC/WB. All comparisons had excellent robust regression coefficients
      except those with POC/WB. CONCLUSIONS AND CLINICAL IMPORTANCE: POC glucometry
      with plasma had excellent agreement with a laboratory standard, as did blood gas
      analysis. POC glucometry with whole blood correlated poorly with a laboratory
      standard. These differences may be clinically important, and could affect
      decisions based on glucose concentrations.

PMID- 18638019
TI  - Detection of Mycobacterium avium subspecies paratuberculosis-specific DNA by PCR
      in intestinal biopsies of dogs.
AB  - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is the cause of
      paratuberculosis. MAP infections have not been reliably detected in dogs, but a
      reemerging debate about the link between MAP and Crohn's disease has renewed
      interest about the occurrence of MAP in pets. HYPOTHESIS: This study was
      undertaken to examine canine intestinal biopsies for the presence of MAP-specific
      DNA. ANIMALS: Forty-two dogs with chronic vomiting, diarrhea, or both; and 14
      dogs with no gastrointestinal disease. METHODS: All dogs with signs of
      gastrointestinal disease had a standard work-up for chronic gastrointestinal
      disease. Endoscopically obtained intestinal biopsies were submitted for
      histopathologic and molecular investigations. Biopsies were screened for MAP
      specific DNA by 3 polymerase chain reaction (PCR) methods (nested, seminested,
      and triplex real-time PCR). Samples from control dogs were obtained during
      necropsy. RESULTS: Histopathology of the biopsies was indicative of inflammatory
      bowel disease (IBD) in 17 and neoplasia in 6 dogs. Six dogs showing nonspecific
      changes responded to diet and were classified as having food-responsive
      enteropathy. In 13 dogs a final diagnosis was not established. MAP-specific DNA
      was detected and confirmed by sequencing in 8 dogs (19%). These dogs were
      diagnosed with food-responsive enteropathy (n=3), IBD (n=2), and open diagnosis
      (n=3). MAP-specific DNA was not detected in dogs with no gastrointestinal
      disease. CONCLUSIONS AND CLINICAL IMPORTANCE: MAP-specific DNA was detected in
      approximately one fifth of dogs with chronic gastrointestinal disease and might
      play a role as a pathogenic agent. Apart from animal welfare, the zoonotic aspect
      warrants further studies addressing the viability of MAP organism in canine
      intestinal biopsies by culture.

PMID- 18638020
TI  - Effects of norepinephrine and combined norepinephrine and fenoldopam infusion on
      systemic hemodynamics and indices of renal function in normotensive neonatal
      foals.
AB  - BACKGROUND: Norepinephrine increases arterial blood pressure but may have adverse
      effects on renal blood flow. Fenoldopam, a dopamine-1 receptor agonist, increases
      urine output in normotensive foals. The combination of norepinephrine and
      fenoldopam may lead to improved renal perfusion compared with an infusion of
      norepinephrine alone. The combined effects of these drugs have not been reported
      in the horse. HYPOTHESIS: Norepinephrine will alter the hemodynamic profile of
      foals without affecting renal function. Addition of fenoldopam will change the
      renal profile during the infusions without changing the hemodynamic profile.
      ANIMALS: Five conscious pony foals. METHODS: Each foal received norepinephrine
      (0.3 microg/kg/min), combined norepinephrine (0.3 microg/kg/min) and fenoldopam
      (0.04 microg/kg/min), and a control dose of saline in a masked, placebo
      controlled study. Heart rate (HR), arterial blood pressure (direct), and cardiac
      output (lithium dilution) were measured, and systemic vascular resistance (SVR),
      stroke volume, cardiac index (CI), and stroke volume index were calculated. Urine
      output, creatinine clearance, and fractional excretion of electrolytes were
      measured. RESULTS: Norepinephrine and a combined norepinephrine and fenoldopam
      infusion increased arterial blood pressure, SVR, urine output, and creatinine
      clearance and decreased HR and CI compared with saline. The combination resulted
      in higher HR and lower arterial blood pressure than norepinephrine alone.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Norepinephrine might be useful for
      hypotensive foals, because in normal foals, this infusion rate increases SVR
      without negatively affecting renal function (creatinine clearance increased).
      Fenoldopam does not provide additional benefit to renal function. These findings
      warrant further investigation.

PMID- 18638021
TI  - Serum cardiac troponin I concentration in dogs with ehrlichiosis.
AB  - BACKGROUND: Ehrlichiosis is a multisystemic disease with the potential to cause
      cardiomyocyte injury in naturally infected dogs. HYPOTHESIS: Myocardial injury
      occurs in dogs infected with Ehrlichia canis. ANIMALS: One-hundred and ninety
      four dogs from Brazil with clinical and laboratory abnormalities indicative of
      ehrlichiosis. Sixteen healthy dogs served as controls. METHODS:
      Electrocardiogram, echocardiogram, noninvasive blood pressure measurement, and
      serum cardiac troponin I (cTnI) concentrations were evaluated. Serologic assays
      and PCR determined the exposure and infection status for E. canis, Anaplasma
      spp., Babesia canis vogeli, Bartonella spp., Borrelia burgdorferi, Dirofilaria
      immitis, Ehrlichia chaffeensis, Ehrlichia ewingii, Leishmania chagasi, and
      spotted-fever group Rickettsia. Dogs were assigned to groups according to PCR
      status: E. canis infected, infected with other vector-borne organisms, sick dogs
      lacking PCR evidence for infection, and healthy controls. RESULTS: E. canis
      infected dogs had higher serum cTnI concentrations than controls (median: 0.04
      ng/dL; range 0.04-9.12 ng/dL; control median: 0.04 ng/dL; range: 0.04-0.10 ng/dL;
      P= .012), and acute E. canis infection was associated with myocardial injury
      (odds ratio [OR]: 2.67, confidence interval [CI] 95%: 1.12-6.40, P= .027).
      Severity of anemia was correlated with increased risk of cardiomyocyte damage (r=
      0.84, P< .001). Dogs with clinical signs of systemic inflammatory response
      syndrome (SIRS) were at higher risk for myocardial injury than were other sick
      dogs (OR: 2.55, CI 95%: 1.31-4.95, P= .005). CONCLUSIONS AND CLINICAL IMPORTANCE:
      Acute infection with E. canis is a risk factor for myocardial injury in naturally
      infected Brazilian dogs. Severity of anemia and SIRS might contribute to the
      pathophysiology of myocardial damage.

PMID- 18638024
TI  - Insulin and the constituent branches of the hepatic vagus interact to modulate
      hypothalamic and limbic neuropeptide mRNA expression differentially.
AB  - Insulin and signalling through the vagus nerve act in concert to regulate
      metabolic homeostasis and ingestive behaviour. Our previous studies using
      streptozotocin (STZ)-diabetic rats have shown that hepatic branch vagotomy (HV),
      gastroduodenal branch vagotomy (GV) and capsaicin treatment of the common hepatic
      branch that selectively destroys afferent fibres (CapV), all promote lard, but
      not total, caloric intake to levels similar to those achieved with insulin
      treatment. Because hypothalamic and limbic mRNA expression of neuropeptides
      linked to energy balance is altered by STZ-diabetes and HV, we examined the
      role(s) of insulin and the common hepatic and gastroduodenal branches of the
      vagus nerve and hepatic afferent fibres in the regulation of these neuropeptides
      in rats with high, steady-state corticosterone levels. STZ-diabetic rats were
      prepared with osmotic minipumps containing either saline or insulin and were
      compared with nondiabetic counterparts: half of each group received a vagal
      manipulation, the other half were sham operated. Five days after surgery, rats
      were offered the choice of lard and chow to consume for another 5 days, when
      brains were collected and processed for in situ hybridisation. Paraventricular
      nucleus corticotrophin-releasing factor (CRF) mRNA was elevated by STZ treatment,
      an effect prevented by either insulin treatment or GV. By contrast, CRF mRNA
      expression in the central nucleus of the amygdala and bed nuclei of the stria
      terminalis was unaffected by STZ treatment, but HV and CapV manipulations
      elevated expression in the nondiabetic, but not STZ-diabetic groups. Arcuate
      nucleus neuropeptide Y, but not pro-opiomelanocortin, mRNA expression was
      elevated by STZ treatment and all vagal manipulations; however, exogenous insulin
      treatment failed to prevent this, in keeping with their previously documented
      elevated caloric intake. These results strongly suggest that the gastroduodenal
      branch and hepatic branch proper, which merge to form the common hepatic branch,
      differentially interact with prevailing insulin levels to regulate hypothalamic
      and limbic neuropeptide mRNA expression.

PMID- 18638025
TI  - Gonadotrophin-inhibitory hormone receptor expression in the chicken pituitary
      gland: potential influence of sexual maturation and ovarian steroids.
AB  - Gonadotrophin-inhibitory hormone (GnIH), a hypothalamic RFamide, has been found
      to inhibit gonadotrophin secretion from the anterior pituitary gland originally
      in birds and, subsequently, in mammalian species. The gene encoding a
      transmembrane receptor for GnIH (GnIHR) was recently identified in the brain,
      pituitary gland and gonads of song bird, chicken and Japanese quail. The
      objectives of the present study are to characterise the expression of GnIHR mRNA
      and protein in the chicken pituitary gland, and to determine whether sexual
      maturation and gonadal steroids influence pituitary GnIHR mRNA abundance. GnIHR
      mRNA quantity was found to be significantly higher in diencephalon compared to
      either anterior pituitary gland or ovaries. GnIHR mRNA quantity was significantly
      higher in the pituitaries of sexually immature chickens relative to sexually
      mature chickens. Oestradiol or a combination of oestradiol and progesterone
      treatment caused a significant decrease in pituitary GnIHR mRNA quantity relative
      to vehicle controls. GnIHR-immunoreactive (ir) cells were identified in the
      chicken pituitary gland cephalic and caudal lobes. Furthermore, GnIHR-ir cells
      were found to be colocalised with luteinising hormone (LH)beta mRNA-, or follicle
      stimulating hormone (FSH)beta mRNA-containing cells. GnIH treatment significantly
      decreased LH release from anterior pituitary gland slices collected from sexually
      immature, but not from sexually mature chickens. Taken together, GnIHR gene
      expression is possibly down regulated in response to a surge in circulating
      oestradiol and progesterone levels as the chicken undergoes sexual maturation to
      allow gonadotrophin secretion. Furthermore, GnIHR protein expressed in FSHbeta or
      LHbeta mRNA-containing cells is likely to mediate the inhibitory effect of GnIH
      on LH and FSH secretion.

PMID- 18638026
TI  - Hypothalamic suppressor-of-cytokine-signalling 3 mRNA is elevated and pro
      opiomelanocortin mRNA is reduced during pregnancy in Brandt's voles (Lasiopodomys
      brandtii ).
AB  - Leptin acts within the hypothalamus to diminish food intake. In Brandt's voles
      (Lasiopodomys brandtii), both circulating leptin levels and food intake are
      elevated during pregnancy, suggesting an ineffectiveness of leptin to reduce food
      intake. Diminished hypothalamic leptin receptors and impaired leptin signal
      transduction are characteristic of central leptin resistance. The present study
      aimed to determine whether these characteristic modulations of leptin sensitivity
      occurred in pregnant Brandt's voles. The mRNA expression of the long form of the
      leptin receptor (Ob-Rb), suppressor-of-cytokine-signalling 3 (SOCS3),
      neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC)
      and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus were
      examined on dioestrous, day 5, day 10 and day 18 of pregnancy. Compared to
      controls, there was no significant change in hypothalamic Ob-Rb mRNA during the
      pregnancy. SOCS3 mRNA was increased significantly by 68% on day 10% and 93% on
      day 18 of pregnancy compared to controls. Despite elevated leptin levels, POMC
      mRNA was decreased significantly by 60% on day 18 of pregnancy, whereas no
      differences were found in the mRNA expression of NPY, AgRP and CART in pregnant
      voles compared to controls. The elevation of SOCS3 mRNA together with disrupted
      leptin regulation of neuropeptides in the hypothalamus suggests that leptin
      resistance may develop in pregnant Brandt's voles.

PMID- 18638027
TI  - Dizziness presentations in U.S. emergency departments, 1995-2004.
AB  - OBJECTIVES: The objectives were to describe presentation characteristics and
      health care utilization information pertaining to dizziness presentations in U.S.
      emergency departments (EDs) from 1995 through 2004. METHODS: From the National
      Hospital Ambulatory Medical Care Survey (NHAMCS), patient visits to EDs for
      "vertigo-dizziness" were identified. Sample data were weighted to produce
      nationally representative estimates. Patient characteristics, diagnoses, and
      health care utilization information were obtained. Trends over time were assessed
      using weighted least squares regression analysis. Multivariable logistic
      regression analysis was used to control for the influence of age on the
      probability of a vertigo-dizziness visit during the study time period. RESULTS:
      Vertigo-dizziness presentations accounted for 2.5% (95% confidence interval [CI]
      = 2.4% to 2.6%) of all ED presentations during this 10-year period. From 1995 to
      2004, the rate of visits for vertigo-dizziness increased by 37% and demonstrated
      a significant linear trend (p < 0.001). Even after adjusting for age (and other
      covariates), every increase in year was associated with increased odds of a
      vertigo-dizziness visit. At each visit, a median of 3.6 diagnostic or screening
      tests (95% CI = 3.2 to 4.1) were performed. Utilization of many tests increased
      over time (p < 0.01). The utilization of computerized tomography and magnetic
      resonance imaging (CT/MRI) increased 169% from 1995 to 2004, which was more than
      any other test. The rate of central nervous system diagnoses (e.g.,
      cerebrovascular disease or brain tumor) did not increase over time. CONCLUSIONS:
      In terms of number of visits and important utilization measures, the impact of
      dizziness presentations on EDs is substantial and increasing. CT/MRI utilization
      rates have increased more than any other test.

PMID- 18638028
TI  - Simulation in graduate medical education 2008: a review for emergency medicine.
AB  - Health care simulation includes a variety of educational techniques used to
      complement actual patient experiences with realistic yet artificial exercises.
      This field is rapidly growing and is widely used in emergency medicine (EM)
      graduate medical education (GME) programs. We describe the state of simulation in
      EM resident education, including its role in learning and assessment. The use of
      medical simulation in GME is increasing for a number of reasons, including the
      limitations of the 80-hour resident work week, patient dissatisfaction with being
      "practiced on," a greater emphasis on patient safety, and the importance of early
      acquisition of complex clinical skills. Simulation-based assessment (SBA) is
      advancing to the point where it can revolutionize the way clinical competence is
      assessed in residency training programs. This article also discusses the design
      of simulation centers and the resources available for developing simulation
      programs in graduate EM education. The level of interest in these resources is
      evident by the numerous national EM organizations with internal working groups
      focusing on simulation. In the future, the health care system will likely follow
      the example of the airline industry, nuclear power plants, and the military,
      making rigorous simulation-based training and evaluation a routine part of
      education and practice.

PMID- 18638029
TI  - Predictors of mortality in patients with delirium tremens.
AB  - OBJECTIVES: The objectives were to identify factors that may help predict
      mortality for patients with delirium tremens (DT). METHODS: The authors conducted
      a 1:1 gender- and age-matched case-control study of patients hospitalized for DT.
      Using McNemar chi-square tests and conditional logistic regression (CLR), risk
      factors for death, including demographics, location of diagnosis, vital sign
      derangements, treatment methods, and comorbid conditions, were evaluated. Crude
      and adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported.
      RESULTS: Thirty-five patients with DT died between January 2000 and June 2006.
      The majority (31; 88.6%) were male with a mean (+/-standard deviation [SD]) age
      of 51.7 (+/-7.6) years. Hyperthermia in the first 24 hours of DT diagnosis (OR =
      10.0, 95% CI = 2.3 to 42.7), persistent tachycardia (OR = 24.0, 95% CI = 3.3 to
      177.4), and use of restraints (OR = 7.50, 95% CI = 1.7 to 32.8) were associated
      with increased mortality by univariate analysis, while an emergency department
      (ED) diagnosis of DT (OR = 0.18, 95% CI = 0.05 to 0.6) and use of clonidine (OR =
      0.10, 95% CI = 0.01 to 0.78) were associated with decreased mortality. In the CLR
      model, restraint use and hyperthermia were the only variables that remained
      significant (OR = 5.8, 95% CI = 1.0 to 32.2; and OR = 6.1, 95% CI = 1.2 to 30.4,
      respectively). CONCLUSIONS: The use of restraints and hyperthermia is associated
      with increased odds of death for patients with DT. This study highlights the need
      for further research into modifiable factors influencing mortality from DT.

PMID- 18638030
TI  - A comparison of door-to-balloon times and false-positive activations between
      emergency department and out-of-hospital activation of the coronary
      catheterization team.
AB  - OBJECTIVES: The objectives were to compare the proportion of false-positive
      activations and intervention times between emergency department (ED) and field
      based activation of the coronary catheterization laboratory (cath) team for
      emergency medical services (EMS) patients identified by out-of-hospital (OOH) 12
      lead electrocardiogram (ECG) with ST-segment elevation myocardial infarction
      (STEMI). METHODS: This was a retrospective review of prospectively collected
      continuous quality improvement data at a single, urban, academic medical center.
      By protocol, weekday activation of the cath team occurred based on OOH
      notification of a computer-interpreted OOH ECG indicating potential STEMI. Night
      and weekend activation occurred at the discretion of the attending emergency
      physician (EP) after advanced ED notification and after patient arrival and
      assessment. Basic demographic information and cardiac risk factors were recorded,
      as well as door-to-balloon (DTB) and ultimate diagnosis. RESULTS: From May 2007
      through March 2008, there were 23 field activations and 33 ED activations. There
      was no difference in demographic or clinical characteristics between the two
      groups. In the field activation group, 9/23 (39%) were false-positives, while
      3/33 (9%) were false-positives in the ED activation group (30% higher absolute
      difference in the field activation group, 95% confidence interval [CI] = 8% to
      52%, p = 0.02). OOH times and time spent in the ED were similar between the two
      groups. DTB times were 77 minutes for field activation and 68 minutes for ED
      activation, respectively (difference 9 minutes, 95% CI = -9 to 27). CONCLUSIONS:
      Emergency physician activation of the cath team results in a lower proportion of
      false-positive activations without clearly sacrificing DTB time when compared to
      field activation based solely on the results of the OOH ECG.

PMID- 18638031
TI  - Building a simulation-based crisis resource management course for emergency
      medicine, phase 1: Results from an interdisciplinary needs assessment survey.
AB  - INTRODUCTION: Emergency department (ED) resuscitation requires the coordinated
      efforts of an interdisciplinary team. Human errors are common and have a negative
      impact on patient safety. Although crisis resource management (CRM) skills are
      utilized in other clinical domains, most emergency medicine (EM) caregivers
      currently receive no formal CRM training. OBJECTIVES: The objectives were to
      compile and compare attitudes toward CRM training among EM staff physicians,
      nurses, and residents at two Canadian academic teaching hospitals. METHODS:
      Emergency physicians (EPs), residents, and nurses were asked to complete a Web
      survey that included Likert scales and short answer questions. Focus groups and
      pilot testing were used to inform survey development. Thematic content analysis
      was performed on the qualitative data set and compared to quantitative results.
      RESULTS: The response rate was 75.7% (N = 84). There was strong consensus
      regarding the importance of core CRM principles (i.e., effective communication,
      team leadership, resource utilization, problem-solving, situational awareness) in
      ED resuscitation. Problems with coordinating team actions (58.8%), communication
      (69.6%), and establishing priorities (41.3%) were among factors implicated in
      adverse events. Interdisciplinary collaboration (95.1%), efficiency of patient
      care (83.9%), and decreased medical error (82.6%) were proposed benefits of CRM
      training. Communication between disciplines is a barrier to effective ED
      resuscitation for 94.4% of nurses and 59.7% of EPs (p = 0.008). Residents
      reported a lack of exposure to (64.3%), yet had interest in (96.4%) formal CRM
      education using human patient simulation. CONCLUSIONS: Nurses rate communication
      as a barrier to teamwork more frequently than physicians. EM residents are keen
      to learn CRM skills. An opportunity exists to create a novel interdisciplinary
      CRM curriculum to improve EM team performance and mitigate human error.

PMID- 18638032
TI  - A theme-based hybrid simulation model to train and evaluate emergency medicine
      residents.
AB  - OBJECTIVES: The authors sought to design an integrated theme-based hybrid
      simulation experience to educate and evaluate emergency medicine (EM) residents,
      to measure the Accreditation Council for Graduate Medical Education (ACGME)
      competencies using this simulation model, to measure the impact of the simulation
      experience on resident performance on written tests, and to measure resident
      satisfaction with this simulation experience. METHODS: A theme-based hybrid
      simulation model that takes advantage of multiple simulation modalities in a
      concentrated session was developed and executed to both educate and evaluate EM
      residents. Simulation days took place at an integrated simulation center and
      replaced one 5-hour didactic block per quarter. Modified competency checklists
      were used to evaluate residents based on ACGME competencies. Written tests were
      administered before, during, and after simulation days. Residents were given the
      opportunity to evaluate the simulation days using standard residency program
      evaluation tools. RESULTS: The model was proven feasible. Core competencies were
      measured using the model, which was executed on four occasions in 2007. Most
      residents met expectations based on objective checklist criteria and subjective
      assessment by an observing faculty member. Data from the written tests showed no
      overall difference in scores measured before, during, or after the simulation
      days. The simulation model was rated highly useful by the residents. CONCLUSIONS:
      With the use of a highly developed simulation center and an organized, theme
      based, hybrid simulation model that takes advantage of multiple simulation
      modalities, the authors were able to successfully develop an educational model to
      both train and evaluate EM residents with a high degree of resident satisfaction.

PMID- 18638034
TI  - Decreasing lab turnaround time improves emergency department throughput and
      decreases emergency medical services diversion: a simulation model.
AB  - BACKGROUND: The effect of decreasing lab turnaround times on emergency department
      (ED) efficiency can be estimated through system-level simulation models and help
      identify important outcome measures to study prospectively. Furthermore, such
      models may suggest the advantage of bedside or point-of-care testing and how they
      might affect efficiency measures. OBJECTIVES: The authors used a sophisticated
      simulation model in place at an adult urban ED with an annual census of 55,000
      patient visits. The effect of decreasing turnaround times on emergency medical
      services (EMS) diversion, ED patient throughput, and total ED length of stay
      (LOS) was determined. METHODS: Data were generated by using system dynamics
      analytic modeling and simulation approach on 90 separate days from December 2,
      2007, through February 29, 2008. The model was a continuous simulation of ED
      flow, driven by real-time actual patient data, and had intrinsic error checking
      to assume reasonable goodness-of-fit. A return of complete laboratory results
      incrementally at 120, 100, 80, 60, 40, 20, and 10 minutes was compared. Diversion
      calculation assumed EMS closure when more than 10 patients were in the waiting
      room and 100% ED bed occupancy had been reached for longer than 30 minutes, as
      per local practice. LOS was generated from data insertion into the patient flow
      stream and calculation of time to specific predefined gates. The average accuracy
      of four separate measurement channels (waiting room volume, ED census, inpatient
      admit stream, and ED discharge stream), all across 24 hours, was measured by
      comparing the area under the simulated curve against the area under the measured
      curve. Each channel's accuracy was summed and averaged for an overall accuracy
      rating. RESULTS: As lab turnaround time decreased from 120 to 10 minutes, the
      total number of diversion days (maximum 57 at 120 minutes, minimum 29 at 10
      minutes), average diversion hours per day (10.8 hours vs. 6.0 hours), percentage
      of days with diversion (63% vs. 32%), and average ED LOS (2.77 hours vs. 2.17
      hours) incrementally decreased, while average daily throughput (104 patients vs.
      120 patients) increased. All runs were at least 85% accurate. CONCLUSIONS: This
      simulation model suggests compelling improvement in ED efficiency with decreasing
      lab turnaround time. Outcomes such as time on EMS diversion, ED LOS, and ED
      throughput represent important but understudied areas that should be evaluated
      prospectively. EDs should consider processes that will improve turnaround time,
      such as point-of-care testing, to obtain these goals.

PMID- 18638035
TI  - Promoting teamwork: an event-based approach to simulation-based teamwork training
      for emergency medicine residents.
AB  - The growing complexity of patient care requires that emergency physicians (EPs)
      master not only knowledge and procedural skills, but also the ability to
      effectively communicate with patients and other care providers and to coordinate
      patient care activities. EPs must become good team players, and consequently an
      emergency medicine (EM) residency program must systematically train these skills.
      However, because teamwork-related competencies are relatively new considerations
      in health care, there is a gap in the methods available to accomplish this goal.
      This article outlines how teamwork training for residents can be accomplished by
      employing simulation-based training (SBT) techniques and contributes tools and
      strategies for designing structured learning experiences and measurement tools
      that are explicitly linked to targeted teamwork competencies and learning
      objectives. An event-based method is described and illustrative examples of
      scenario design and measurement tools are provided.

PMID- 18638036
TI  - Educational and research implications of portable human patient simulation in
      acute care medicine.
AB  - Advanced medical simulation has become widespread. One development, the
      adaptation of simulation techniques and manikin technologies for portable
      operation, is starting to impact the training of personnel in acute care fields
      such as emergency medicine (EM) and trauma surgery. Unencumbered by cables and
      wires, portable simulation programs mitigate several limitations of traditional
      (nonportable) simulation and introduce new approaches to acute care education and
      research. Portable simulation is already conducted across multiple specialties
      and disciplines. In situ medical simulations are those carried out within actual
      clinical environments, while off-site portable simulations take place outside of
      clinical practice settings. Mobile simulation systems feature functionality while
      moving between locations; progressive simulations are longer-duration events
      using mobile simulations that follow a simulated patient through sequential care
      environments. All of these variants have direct applications for acute care
      medicine. Unique training and investigative opportunities are created by portable
      simulation through four characteristics: 1) enhancement of experiential learning
      by reframing training inside clinical care environments, 2) improving simulation
      accessibility through delivery of training to learner locations, 3) capitalizing
      on existing care environments to maximize simulation realism, and 4) provision of
      improved training capabilities for providers in specialized fields. Research
      agendas in acute care medicine are expanded via portable simulation's
      introduction of novel topics, new perspectives, and innovative methodologies.
      Presenting opportunities and challenges, portable simulation represents an
      evolutionary progression in medical simulation. The use of portable manikins and
      associated techniques may increasingly complement established instructional
      measures and research programs at acute care institutions and simulation centers.

PMID- 18638037
TI  - Estimating the size and dynamics of an injecting drug user population and
      implications for health service coverage: comparison of indirect prevalence
      estimation methods.
AB  - AIMS: (i) To compare indirect estimation methods to obtain mean injecting drug
      use (IDU) prevalence for a confined geographic location; and (ii) to use these
      estimates to calculate IDU and injection coverage of a medically supervised
      injecting facility. DESIGN: Multiple indirect prevalence estimation methods.
      SETTING: Kings Cross, Sydney, Australia. PARTICIPANTS: IDUs residing in Kings
      Cross area postcodes recorded in surveillance data of the Sydney Medically
      Supervised Injecting Centre (MSIC) between November 2001 and October 2002.
      MEASUREMENTS: Two closed and one open capture-recapture (CRC) models (Poisson
      regression, truncated Poisson and Jolly-Seber, respectively) were fitted to the
      observed data. Multiplier estimates were derived from opioid overdose mortality
      data and a cross-sectional survey of needle and syringe programme attendees. MSIC
      client injection frequency and the number of needles and syringes distributed in
      the study area were used to estimate injection prevalence and injection coverage.
      FINDINGS: From three convergent estimates, the mean estimated size of the IDU
      population aged 15-54 years was 1103 (range 877-1288), yielding a population
      prevalence of 3.6% (2.9-4.3%). Mean IDU coverage was 70.7% (range 59.1-86.7%) and
      the mean adjusted injection coverage was 8.8% (range 7.3-10.8%). Approximately
      11.3% of the total IDU population were estimated to be new entrants to the
      population per month. CONCLUSIONS: Credible local area IDU prevalence estimates
      using MSIC surveillance data were obtained. MSIC appears to achieve high coverage
      of the local IDU population, although only an estimated one in 10 injections
      occurs at MSIC. Future prevalence estimation efforts should incorporate open
      models to capture the dynamic nature of IDU populations.

PMID- 18638038
TI  - Racial disparity in stroke risk factors: the Berlin-Ibadan experience; a
      retrospective study.
AB  - BACKGROUND: Different workers have reported racial disparities in the
      distribution of risk factors for stroke and stroke subtype (ischemic vs
      hemorrhagic). No transcultural transnational studies have been conducted to
      confirm and relate these disparities to one another. Our objective was to
      identify differences in the distribution of risk factors for stroke and stroke
      subtypes among urban-dwelling stroke patients in Nigeria, a developing country,
      and Germany, an industrialized country. METHODS: Consecutive stroke patients in
      Ibadan (100) and Berlin (103) were studied. Their hospital records were screened
      to identify documented vascular risk factors and stroke subtype. RESULTS: The
      stroke patients in Ibadan were younger than those in Berlin (t = 4.940, P =
      0.000). Hypertension was significantly more common in Ibadan while cigarette
      smoking, dyslipidemia, atherosclerosis, and cardiac factors were significantly
      more frequent in Berlin. Cerebral infarction was more common in Berlin (80%) than
      in Ibadan (63%). CONCLUSION: The risk factors associated with cerebral infarction
      were more frequent in Berlin. We suspect that racial disparity in risk factors
      for stroke may account for the difference in proportions of stroke subtype in
      black and white populations. Larger prospective community-based multinational
      multiracial studies are required to confirm these disparities and identify
      possible underlying genetic, dietary, and socio-economic factors.

PMID- 18638039
TI  - Striatal [123I] FP-CIT SPECT demonstrates dopaminergic deficit in a sporadic case
      of Creutzfeldt-Jakob disease.
AB  - BACKGROUND: The frequent occurrence of movement disorders such as myoclonus,
      parkinsonism and dystonia, strongly suggests an involvement of the dopaminergic
      system in sporadic Creutzfeldt-Jakob disease (sCJD), but this issue has not been
      specifically addressed yet. METHODS: We report a patient who after a sub-acute
      focal clinical onset, developed the full clinical picture of probable sCJD. Given
      the early unilateral right extrapyramidal rigidity, the patient was assessed by
      single-photon emission computed tomography of the dopamine transporter (DAT)
      using [123I] FP-CIT. RESULTS: DAT-scan demonstrated reduced values of presynaptic
      receptorial trace in the putamen, particularly on the left side, consistent with
      functional putaminal dopaminergic presynaptic alteration. CONCLUSIONS: The
      present observation emphasizes the possible role of DAT imaging studies in the
      investigation of the pathogenesis of movement disorders in CJD.

PMID- 18638040
TI  - Efficacy of a soft hand brace and a wrist splint for carpal tunnel syndrome: a
      randomized controlled study.
AB  - OBJECTIVE: To examine, in a randomized, controlled, single blinded trial, the
      efficacy of a soft hand brace and a wrist splint for carpal tunnel syndrome
      (CTS). METHODS: We randomized 120 patients with CTS into a group wearing the soft
      hand brace MANU and into another group wearing the wrist splint CAMP TIELLE at
      night for 3 months. We re-evaluated the patients after 3 (T1) and 9 months (T2).
      The primary efficacy measures were changes in scores of Boston Carpal Tunnel
      Questionnaire (BCTQ) and in Visual Analogical Scale (VAS) for pain and
      paresthesias. RESULTS: At T1, both groups showed a significant reduction in
      symptomatic and functional BCTQ (T0-T1 differences: MANU BCTQ sympt: 0.88 (0.68
      1.08), funct: 0.45 (0.19-0.72); TIELLE BCTQ sympt: 0.78 (0.55-1.01), funct: 0.41
      (0.22-0.59). At T2, a less evident benefit on symptoms persisted in both groups,
      except for pain VAS score that was significantly reduced only in the CAMP TIELLE
      group. No significant functional benefits persisted in either group. There were
      no differences in BCTQ and VAS scores between the two groups at T1 and T2
      compared with that at baseline. CONCLUSIONS: A 3-month treatment with either the
      hand brace or the wrist splint induces a symptomatic and functional benefit in
      patients with CTS.

PMID- 18638041
TI  - The occurrence and characteristics of auras in a large epilepsy cohort.
AB  - OBJECTIVES: Despite several studies, estimates of the frequency with which auras
      occur in conjunction with epilepsy continue to be imprecise. The aim of this
      study was to assess the occurrence and characteristics of auras in a large
      population-based epilepsy cohort. MATERIALS AND METHODS: Subjects with verified
      epilepsy were recruited from population-based twin registries in the USA, Denmark
      and Norway. Using a structured interview in which a list of auras was provided,
      subjects were asked about the warning symptoms preceding their epileptic attacks.
      RESULTS: 31% of the total sample (n = 1897) and 39% of those with active epilepsy
      (n = 765) had experienced an aura. Six percent reported more than one type. Non
      specified auras were most frequently reported (35%), followed by somatosensory
      (11%) and vertiginous (11%). While the majority of those reporting auras (59%)
      had focal epilepsies, auras of a mostly non-specific nature were experienced by
      13% of those with generalized epilepsies. CONCLUSION: Auras serve an important
      purpose in that they may prevent seizure-related injuries and could provide an
      indication as to where the seizures originate. The occurrence of auras often is
      underestimated, especially in children and those with learning disabilities.

PMID- 18638042
TI  - Serum interleukin-6 is elevated in symptomatic carotid bifurcation disease.
AB  - INTRODUCTION: The levels of circulating proinflammatory cytokines may express the
      extent of the inflammatory response and their participation in plaque progression
      and rupture needs to be evaluated. We aimed to investigate differences in
      circulating levels of proinflammatory cytokines and in plaque infiltration by
      macrophages between patients undergoing carotid endarterectomy for symptomatic
      and asymptomatic carotid atherosclerotic disease. METHODS: One hundred nineteen
      patients (91 men and 28 women; mean age 66 +/- 8 years; range 42-83 years) who
      underwent carotid endarterectomy for significant (>70%) carotid bifurcation
      stenosis were enrolled in this study. Patients were characterized as symptomatic
      (n = 62) or asymptomatic (n = 57) after neurological examination. Serum levels of
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, serum
      amyloid A (SAA), and high-sensitivity C-reactive protein (hs-CRP) were evaluated.
      Macrophage infiltration of the plaque was assessed quantitatively from
      endarterectomy specimens using the monoclonal antibody CD68. RESULTS: Serum IL-6
      levels were significantly higher in patients with symptomatic compared with those
      with asymptomatic carotid disease (3.3 [2.0-6.5] pg/ml vs 2.5 [1.9-4.1] pg/ml, P
      = 0.02). TNF-alpha, IL-1beta, SAA, and hs-CRP levels did not differ significantly
      between the two groups. Symptomatic patients had also more intense macrophage
      accumulation in the carotid plaque compared with asymptomatic patients (0.6 +/-
      0.1% vs 0.4 +/- 0.1%, P < 0.001). Although there were correlations between the
      levels of the different inflammatory markers, there were no correlation between
      any of them and the extent of plaque macrophage infiltration. CONCLUSION:
      Patients with symptomatic carotid atherosclerotic disease have elevated serum IL
      6 levels compared with asymptomatic patients. Symptomatic patients have also more
      intense macrophage infiltration of the atherosclerotic plaque suggesting that
      inflammatory process may contribute to the destabilization of the carotid plaque.

PMID- 18638043
TI  - High insulin levels are positively associated with peripheral nervous system
      function.
AB  - OBJECTIVE: The aim of this study was to analyze peripheral nervous system (PNS)
      function in overweight and obese individuals. MATERIALS AND METHODS: Forty-four
      adult non-diabetic overweight individuals were recruited. Peroneal motor nerve
      conduction and radial, sural, and medial plantar sensory nerve conduction were
      studied. Insulin and glucose levels were determined twice (over a 2- to 3-year
      period) with an oral glucose tolerance test (OGTT). Multiple stepwise linear
      regression models adjusted for age, height, weight, and skin temperature were
      used to analyze the data. RESULTS: Analysis revealed that baseline insulin levels
      measured 120 min after an OGTT explained 18% of the variation in peroneal F-wave
      minimum latency, 8% of peroneal F-wave maximum latency variation, 15% of sural
      sensory latency variation, 13% of sural sensory nerve conduction velocity (NCV)
      variation, and 10% of the variation in medial plantar sensory NCV. DISCUSSION AND
      CONCLUSION: Our study shows that serum insulin levels measured 120 min after an
      OGGT are positively associated with PNS function. High insulin levels without
      notably high glucose levels appear to be beneficial for the function of the PNS.

PMID- 18638044
TI  - The complex and untidy science of childhood obesity mirrors the complexity of
      practice.

PMID- 18638045
TI  - Evaluation of a pilot hospital-based community program implementing fitness and
      nutrition education for overweight children.
AB  - PURPOSE: Evaluate the effect of the Kids Living Fit hospital-based intervention
      on body mass index (BMI) percentile, adjusted for age (months) and gender in
      children ages 8-12 years with BMI percentiles > or = 85. DESIGN AND METHODS:
      Twelve weekly exercise sessions and three nutrition presentations were held.
      Nurses recorded BMI and waist circumference at baseline, week 12, and week 24.
      Participants completed food and activity diaries. RESULTS: Of the 32 participants
      enrolled, 16 completed all outcome measures and experienced a decrease in average
      BMI, BMI percentile, and waist circumference between baseline and weeks 12 and
      24. PRACTICE IMPLICATIONS: Hospitals can offer exercise and nutrition programs to
      decrease childhood obesity in their communities.

PMID- 18638047
TI  - Pediatric hyperlipidemia: child and adolescent disease understandings and
      perceptions about dietary adherence.
AB  - PURPOSE: Pediatric hyperlipidemia increases cardiovascular disease risk. The
      cornerstone of treatment is a restrictive, lipid-lowering diet. Child disease
      understandings and perceptions of dietary adherence were explored, a secondary
      aim of the Endothelial Assessment of Risk from Lipids in Youth trial. DESIGN AND
      METHODS: Focus groups and individual interviews were conducted with participants,
      ages 9-20 years (n = 50). Data were thematically analyzed. FINDINGS: Adherence is
      influenced by individual characteristics (developmental level, knowledge), in the
      context of social interactions (family modeling, peer relationships, school).
      PRACTICAL IMPLICATIONS: Dietary practices are developed within social
      interactions. Interventions promoting adherence must consider children within
      their social contexts.

PMID- 18638046
TI  - Ecological differences in weight, length, and weight for length of Mexican
      American children in the WIC program.
AB  - PURPOSE: Examine factors common in the environments of children who obtain
      services from a WIC program to determine if differences in
      ecological/environmental factors can be found in the children who differ in
      weight, length, and weight for length. DESIGN AND METHODS: Cross-sectional study
      of 300 children, 100 each who were stunted, normal weight for length, or
      overweight. Instruments used were NCATS, ARSMA II, 24-hr diet recall, and Baecke
      Activity Questionnaire. RESULTS: Significant differences were present in
      children's diet, parents' BMI, parents' generation in United States, parents'
      activity levels, and maternal-child relationship. PRACTICE IMPLICATIONS:
      Encourage parents to adopt family approaches to encourage normal body size in
      children.

PMID- 18638048
TI  - Healthcare providers' perceptions of the factors contributing to infant obesity
      in a low-income Mexican American community.
AB  - PURPOSE: To examine healthcare professionals' perceptions of Mexican American
      infant feeding practices and obesity. DESIGN AND METHODS: Five provider focus
      groups (n = 38 providers) were conducted in two agencies in the Denver area on
      the topic of contributors to childhood obesity in the Mexican American community.
      RESULTS: Healthcare providers believe obesity in Mexican American infants is
      related to: (a) a chubby baby being a healthy baby, (b) introducing complementary
      foods early, (c) extended family members' infant feeding practices, (d) offering
      infants high-calorie foods, and (e) prolonged bottle feeding and sweet beverages.
      Providers reported ambivalence regarding their role in addressing infant obesity.
      PRACTICE IMPLICATIONS: Healthcare providers working with Mexican American
      families should deliver consistent, culturally specified messages regarding
      infant feeding and activity practices.

PMID- 18638049
TI  - Social implications of overweight and obesity in children.
AB  - PURPOSE: To elucidate some of the social impacts that overweight and obesity in
      children has on families. Healthcare practitioners may be unaware of these
      impacts if not similarly affected. DESIGN: Qualitative semistructured, interview
      based study. METHODS: A purposive sample of parents (n = 58) with overweight and
      obese children (n = 48) from three areas in the United Kingdom was used. Analysis
      was thematic and iterative, underpinned by Grounded Theory. RESULTS: There are
      many social situations that have an impact on the child directly
      (stigmatization), on parents (blame), and on the family in general (being
      ostracized). PRACTICE IMPLICATIONS: Seeing the child and his/her family in a
      broader context with improved understanding of the complexity of raising an
      overweight child.

PMID- 18638050
TI  - Dietary and physical activity patterns: examining fathers' perspectives.
AB  - PURPOSE: Obesity adversely affects children, yet limited information is available
      on the familial environmental influence of fathers. The purpose of this study was
      to examine fathers' influences on their children's eating and activity patterns.
      DESIGN AND METHODS: Participants for this mixed methods study was a convenience
      sample of 51 multi-ethnic fathers of children 8-12 years of age, who completed
      surveys addressing dietary and physical activity behaviors. RESULTS: An
      association was found between fathers' and children's weight status. Half the
      children snacked without parental guidance. PRACTICE IMPLICATIONS: Nurses need to
      assist children and their families to develop effective weight management
      strategies.

PMID- 18638051
TI  - Pilot study of an individually tailored educational program by mail to promote
      healthy weight in Chinese American children.
AB  - PURPOSE: To test the feasibility and impact of an individually tailored
      educational intervention to promote healthy weight in Chinese American children
      (ages 8-10). DESIGN: A pre- and post-test study (N = 57) using standardized
      instruments to measure children's usual food choices, knowledge of nutrition and
      physical activity needs, and time spent engaging in physical and sedentary
      activities. RESULTS: We found improvement after the intervention in all three
      areas. PRACTICE IMPLICATIONS: Healthcare providers need to provide parents and
      children with specific recommendations regarding children's weight statuses,
      dietary intake, and levels of activity.

PMID- 18638052
TI  - Ask the expert. Legislative efforts to combat childhood obesity.

PMID- 18638053
TI  - Collaborative practice. A collaborative approach to nutritional counseling of the
      overweight child.

PMID- 18638054
TI  - Family-centered care. Assessing and surmounting barriers to eating and activity
      changes in overweight youth.

PMID- 18638056
TI  - Statistical significance, power and sample size--Part 2.

PMID- 18638057
TI  - Tibial tuberosity avulsion fracture in dogs: a review of 59 dogs.
AB  - OBJECTIVES: To evaluate the high incidence of tibial tuberosity avulsion fracture
      diagnosed in skeletally immature Staffordshire bull terriers presenting to a UK
      animal welfare charity hospital. METHODS: A retrospective review of tibial
      tuberosity avulsion fractures treated by the hospital between 2002 and 2007.
      RESULTS: Sixty-five tibial tuberosity avulsion fractures were recorded in 59
      dogs. Fifty-one tibial tuberosity avulsion fracture-affected dogs (86 per cent)
      were Staffordshire bull terriers. Dogs sustaining tibial tuberosity avulsion
      fractures had median and mean ages of five and 4.9 months, respectively (range
      three to 10 months). Where recorded, injury was associated with a short fall or
      jump (typically 3 to 4 feet) in 29 of 50 dogs. Three fracture patterns were
      recorded: 37 stifles sustained isolated tibial tuberosity avulsion fracture; 15
      stifles sustained tibial tuberosity avulsion fracture accompanied by separation
      of the proximal tibial epiphysis; in 13 stifles epiphyseal separation extended to
      produce Salter-Harris type II fracture of the caudal tibial metaphysis. On
      analysis of the hospital database, tibial tuberosity avulsion fracture was a
      reason for presentation in 51 (3.3 per cent) of 1536 Staffordshire bull terriers,
      but only five (0.18 per cent) of 2815 other breed dogs, registered under the age
      of 12 months during the study period (P<0.001). CLINICAL SIGNIFICANCE:
      Staffordshire bull terriers commonly present with tibial tuberosity avulsion
      fracture, with or without concurrent separation of the proximal tibial epiphysis,
      to this urban charity hospital.

PMID- 18638058
TI  - A retrospective study of canine D-dimer concentrations measured using an
      immunometric "Point-of-Care" test.
AB  - OBJECTIVES: To measure the D-dimer concentrations in both healthy dogs and dogs
      with and without evidence of thromboembolic disease/disseminated intravascular
      coagulation using a "Point-of-Care" test. METHODS: Sixty-seven clinical cases and
      26 healthy dogs were included in this retrospective study. D-dimer was measured
      using the NycoCard D-dimer test. Clinical conditions were categorised based on
      clinical findings, laboratory results, imaging, cytology, histopathology,
      necropsy or a combination of these tests. RESULTS: There were no dogs for which
      the NycoCard D-dimer test did not produce a result. The D-dimer range in
      clinically healthy dogs was 0.1 to 0.5 mg/l (median 0.2 mg/l). In eight of nine
      cases with thromboembolic disease/disseminated intravascular coagulation and 43
      of 58 of the cases without thromboembolic disease/disseminated intravascular
      coagulation , the D-dimer concentrations were greater than those of healthy dogs.
      CLINICAL SIGNIFICANCE: The NycoCard D-dimer test card required no specialised
      equipment and could therefore facilitate rapid screening for thromboembolic
      disease/disseminated intravascular coagulation in first opinion practice.
      Elevations in D-dimer concentration can be found in a number of clinical
      conditions apart from thromboembolic disease/disseminated intravascular
      coagulation and should not therefore be used as the sole basis of diagnosis. D
      dimer may be considered a good screening test for thromboembolic
      disease/disseminated intravascular coagulation as only one case with
      histopathological evidence of thromboembolic disease/disseminated intravascular
      coagulation had a D-dimer concentration in the range seen in healthy dogs.

PMID- 18638059
TI  - Acute necrotising pulmonary vasculitis and pulmonary hypertension in a juvenile
      dog.
AB  - A five-month-old female Jack Russell terrier was presented for investigation of
      acute lethargy, anorexia, coughing, respiratory distress and weakness.
      Examination findings included cyanosis, a grade 3 of 6 systolic heart murmur and
      prolonged capillary refill time. Radiography and echocardiography revealed severe
      pulmonary hypertension, cor pulmonale and right-sided heart failure. Indirect
      measurement of the systolic pulmonary artery pressure estimated pressures over
      100 mmHg. Despite treatment the patient died. Post-mortem examination did not
      identify a congenital cardiovascular anomaly. Histopathology confirmed acute
      necrotising pulmonary arteritis and immunohistochemistry failed to identify any
      immune complex or complement deposition.

PMID- 18638061
TI  - MRSA in a veterinary orthopaedic referral hospital.

PMID- 18638062
TI  - Cerebellar cortical degeneration in two Azores Cattle Dog littermates.

PMID- 18638066
TI  - Advances in stem cell biology - an ASGBI International Conference held at Durham
      University.

PMID- 18638069
TI  - Epithelial stem cells and malignancy.
AB  - The renewal of normal epithelia depends on a small sub-population of cells,
      termed somatic stem cells, whose primary characteristic is an ability for
      indefinite self-renewal. Evidence is accumulating that the growth of tumours
      similarly depends on a sub-population of malignant stem cells, often termed
      tumour-initiating cells. Tumour-initiating sub-populations within solid tumours
      have been identified by their cell surface expression of various phenotypic
      markers and by their ability to regenerate tumours in immune-deficient mice.
      Cells with such clonogenic abilities differ consistently from the remainder of
      the cell population in cellular properties such as size, adhesiveness, dye
      exclusion, and patterns of gene expression. Sub-populations of malignant cells
      freshly isolated from tumours also show differing patterns of expression of
      molecules related to stem cell maintenance and asymmetric division. As the cells
      ultimately responsible for tumour renewal, malignant stem cells appear to form
      the necessary target of therapy but some findings indicate greater resistance of
      these cells to the induction of apoptotic cell death and their potential failure
      to respond effectively to standard therapeutic procedures. Of particular
      interest, cells with clonogenic properties and expression patterns similar to
      those of tumour-initiating cells in vivo persist in malignant cell lines and show
      similar apoptotic resistance. Cell lines may thus provide a model for analysis of
      malignant stem cell properties and may be useful for the development of
      appropriate methods for their elimination.

PMID- 18638068
TI  - G1 to S phase cell cycle transition in somatic and embryonic stem cells.
AB  - It is well known that G1 to S phase transition is tightly regulated by the
      expression and phosphorylation of a number of well-characterized cyclins, cyclin
      dependent kinases and members of the retinoblastoma gene family. In this review
      we discuss the role of these components in regulation of G1 to S phase transition
      in somatic cells and human embryonic stem cells. Most importantly, we discuss
      some new tenable links between maintenance of pluripotency and cell cycle
      regulation in embryonic stem cells by describing the role that master
      transcription factors play in this process. Finally, the differences in cell
      cycle regulation between murine and human embryonic stem cells are highlighted,
      raising interesting questions regarding their biology and stages of embryonic
      development from which they have been derived.

PMID- 18638070
TI  - Small intestinal stem cell markers.
AB  - Stem cells hold great promise for regenerative medicine but remain elusive in
      many tissues, including the small intestine, where it is well accepted that the
      epithelium is maintained by intestinal stem cells located in the crypts. The lack
      of established markers to prospectively identify intestinal stem cells has
      necessitated the use of indirect analysis, e.g. long-term label retention, which
      is based on the hypothesis that intestinal stem cells are slow-cycling. Several
      intestinal stem cell markers have been proposed, including Musashi-1, BMPR1alpha,
      phospho-PTEN, DCAMKL1, Eph receptors and integrins, but their validity, using
      functional and/or lineage tracing assays, has yet to be confirmed. Recently, Lgr5
      has been identified by lineage tracing as an intestinal stem cell marker. In this
      review we summarize what is known about the currently reported intestinal stem
      cell markers and provide a rationale for developing model systems whereby
      intestinal stem cells can be functionally validated.

PMID- 18638067
TI  - Adult stem cell maintenance and tissue regeneration in the ageing context: the
      role for A-type lamins as intrinsic modulators of ageing in adult stem cells and
      their niches.
AB  - Adult stem cells have been identified in most mammalian tissues of the adult body
      and are known to support the continuous repair and regeneration of tissues. A
      generalized decline in tissue regenerative responses associated with age is
      believed to result from a depletion and/or a loss of function of adult stem
      cells, which itself may be a driving cause of many age-related disease
      pathologies. Here we review the striking similarities between tissue phenotypes
      seen in many degenerative conditions associated with old age and those reported
      in age-related nuclear envelope disorders caused by mutations in the LMNA gene.
      The concept is beginning to emerge that nuclear filament proteins, A-type lamins,
      may act as signalling receptors in the nucleus required for receiving and/or
      transducing upstream cytosolic signals in a number of pathways central to adult
      stem cell maintenance as well as adaptive responses to stress. We propose that
      during ageing and in diseases caused by lamin A mutations, dysfunction of the A
      type lamin stress-resistant signalling network in adult stem cells, their
      progenitors and/or stem cell niches leads to a loss of protection against growth
      related stress. This in turn triggers an inappropriate activation or a complete
      failure of self-renewal pathways with the consequent initiation of stress-induced
      senescence. As such, A-type lamins should be regarded as intrinsic modulators of
      ageing within adult stem cells and their niches that are essential for survival
      to old age.

PMID- 18638071
TI  - Colonic and colorectal cancer stem cells: progress in the search for putative
      biomarkers.
AB  - The maintenance of healthy colonic crypts is dependent on the integrity of the
      adult epithelial stem cells located within them. Perturbations in stem cell
      dynamics are generally believed to represent the first step towards colorectal
      tumorigenesis. Experimental manipulation of intestinal stem cells has greatly
      increased our understanding of them, but further progress has been slowed due to
      the absence of a reliable stem cell biomarker. In this review we discuss the
      candidate colonic stem cell biomarkers which have been proposed. Furthermore, we
      investigate the putative biomarkers for so-called colorectal cancer stem cells, a
      highly aggressive subpopulation of cells considered to drive tumour development.

PMID- 18638076
TI  - Is amitriptyline really effective in diarrhoea-predominant irritable bowel
      syndrome?

PMID- 18638075
TI  - Cost-effectiveness analysis on screening for colorectal neoplasm and management
      of colorectal cancer in Asia.
AB  - BACKGROUND: Faecal occult blood testing (FOBT), flexible sigmoidoscopy (FS) and
      colonoscopy are recommended for subjects above 50 years of age for screening for
      colorectal cancer (CRC). AIM: To evaluate the cost-effectiveness of FOBT, FS and
      colonoscopy on the basis of disease prevalence, compliance rate and cost of
      screening procedures in Asian countries. METHODS: A hypothetical population of
      100 000 persons aged 50 undergoes either FOBT annually, FS every 5 years or
      colonoscopy every 10 years until the age of 80 years. Patients with positive FOBT
      or polyp in FS are offered colonoscopy. Surveillance colonoscopy is repeated
      every 3 years. The treatment cost of CRC, including surgery and chemotherapy, was
      evaluated. A Markov model was used to compare the cost-effectiveness of different
      screening strategies. RESULTS: Assuming a compliance rate of 90%, colonoscopy, FS
      and FOBT can reduce CRC incidence by 54.1%, 37.1% and 29.3% respectively. The
      incremental cost-effectiveness ratio (ICER) for FOBT (US$6222 per life-year
      saved) is lower than FS (US$8044 per life-year saved) and colonoscopy (US$7211
      per life-year saved). When the compliance rate drops to 50% and 30%, FOBT still
      has the lowest ICER. CONCLUSION: FOBT is cost-effective compared to FS or
      colonoscopy for CRC screening in average-risk individuals aged from 50 to 80
      years.

PMID- 18638078
TI  - Anti-mycobacterials and Crohn's disease.

PMID- 18638077
TI  - Is amitriptyline really effective in diarrhoea-predominant irritable bowel
      syndrome?: authors' reply.

PMID- 18638079
TI  - Anti-mycobacterials and Crohn's disease: author's reply.

PMID- 18638081
TI  - Exercise and dialysis.
AB  - Fortunately, the literature on exercise among patients on hemodialysis has grown
      too broad to be included in a single review. The focus of this review is on
      interventional studies, with an emphasis on those studies that included a control
      group. The good news is that there is ample evidence that exercise can improve
      fitness (VO(2) peak), physical functioning, and some cardiovascular risk factors
      in the dialysis population. However, there have been few comparative studies, and
      there is no consensus regarding the most beneficial regimen or the one most
      acceptable to large numbers of patients. A new set of recommendations from the
      American College of Sports Medicine and the American Heart Association for older
      individuals and individuals with chronic diseases is relevant for our patient
      population and can be used to guide exercise prescription until disease-specific
      data are available to fill the gap.

PMID- 18638080
TI  - The International Quotidian Dialysis Registry: Annual report 2008.
AB  - Alternative hemodialysis (HD) schedules, including short-daily and nocturnal HD,
      continue to proliferate, with the hope of offering improved patient outcomes.
      Three nights per week and every other night, nocturnal HD are now being provided
      to more patients worldwide, both at home and in-center. However, alternative HD
      schedules are still experimental in most centers, and studies establishing the
      efficacy of these therapies with respect to major clinical outcomes are needed.
      Endorsed by the National Institutes of Health, the International Quotidian
      Dialysis Registry is an international collaboration that was established in 2002
      to prospectively study large numbers of patients treated with alternate HD
      schedules. The Registry will ultimately allow alternate HD modalities to be
      compared to conventional thrice-weekly HD with respect to clinical endpoints,
      including mortality, using a prospective cohort study. To date, the Registry has
      enrolled 182, 1193, and 740 subjects from Canada, the United States, and
      Australia, respectively. This report is the fourth annual update and describes
      recruitment progress, baseline characteristics of enrolled patients, and
      worldwide prescription patterns.

PMID- 18638082
TI  - Dialysis disequilibrium syndrome and other treatment complications of extreme
      uremia: a rare occurrence yet not vanished.
AB  - Severe uremia is now a rare occurrence in most developed nations, and yet is
      still present in many countries of the world. It includes clinical manifestations
      such as calciphylaxis and uremic frost, which are now rarely seen. Patients with
      extremely high levels of blood urea nitrogen (above 175 mg/dL) are at a higher
      risk of experiencing first-time hemodialysis-related complications, in particular
      dialysis disequilibrium syndrome (DDS). DDS is a central nervous disorder
      characterized by a wide variety of neurological symptoms that range from nausea
      and vomiting to even death due to cerebral edema. There are 2 main theories to
      explain its pathophysiology: the reverse urea effect, which considers that the
      shift of urea between brain intracellular space and plasma is not immediate,
      causing a higher concentration of urea within the brain and leading to cerebral
      edema. The second theory considers that after hemodialysis, patients have
      transient paradoxical metabolic acidosis within the central nervous system,
      displacing Na(+) and K(+) from organic anions, making them osmotically active and
      again leading to cerebral edema. The main goal is to prevent the occurrence of
      DDS, for which there are several proposed measures including continuous renal
      replacement therapies. Once established, treatment should be focused on
      supportive therapy. Another uncommon phenomenon described in patients who
      initiate hemodialysis is transient pulmonary leukocyte margination, which in
      conjunction with an inflammatory milieu, may lead to non-cardiogenic pulmonary
      edema. We present the case of a young adult with severe uremia who, despite
      application of recommended measures, developed DDS and non-cardiogenic pulmonary
      edema.

PMID- 18638083
TI  - Practical guidance for dialyzing a hemodialysis patient following acute brain
      injury.
AB  - The incidence of acute brain injury in chronic hemodialysis patients is
      increasing, as the dialysis population is becoming increasingly older, often
      hypertensive, at risk of ischemic and/or hemorrhagic stroke, and subdural
      hemorrhage. Standard intermittent hemodialysis treatments typically lead to an
      increase in cerebral swelling, which can exacerbate underlying cerebral damage.
      In critically ill patients, continuous modes of renal replacement therapy may be
      required, but depending upon the clinical condition, simple modifications to
      standard intermittent therapies may suffice, and allow effective delivery of
      renal replacement therapy, but ensure that patient outcomes both in terms of
      mortality and residual functional brain damage is no different between those with
      normal renal function and those on the chronic dialysis program.

PMID- 18638084
TI  - Dialysis disequilibrium syndrome presenting as a focal neurological deficit.
AB  - We report a patient suffering from chronic kidney disease who presented to us
      with severe pulmonary edema. His clinical, laboratory, and sonological parameters
      were suggestive of end-stage renal disease. Hemodialysis was initiated, and after
      48 hours (3 sessions of hemodialysis) he became drowsy and a neurological
      examination revealed left upper limb monoplegia with left facial palsy. Urgent
      computerized tomography scan of the brain revealed diffuse hypodensity in the
      cerebral white matter bilaterally, and brain magnetic resonance imaging showed
      diffuse hyperintensity in the cerebral white matter bilaterally, right internal
      capsule and external capsule on fluid attenuated inversion recovery and T2
      sequences (hypointense on T1 sequence). He made a gradual but complete
      neurological recovery and was discharged 2 weeks later with normal neurological
      status. A repeat brain magnetic resonance imaging on follow-up 6 weeks later
      revealed complete resolution of the white matter abnormalities.

PMID- 18638085
TI  - Severe jaw enlargement associated with uremic hyperparathyroidism.
AB  - Marked enlargement of the jaws is a rare complication of renal osteodystrophy.
      This report describes a localized enlargement of the mandible due to a brown
      tumor in a patient undergoing chronic hemodialysis. Literature on jaw involvement
      in secondary hyperparathyroidism is reviewed.

PMID- 18638086
TI  - Ventriculo-peritoneal shunt infection in a patient on hemodialysis.
AB  - Sepsis is an important and serious complication in hemodialysis (HD) patients.
      Here we report on a case of spina bifida with ventriculo-peritoneal (VP) shunt
      infection who was on HD and underwent at least 5 months of investigations before
      a source of the infection was found and eventually treated successfully. We
      believe this to be the first reported case of VP shunt-associated sepsis in a
      patient on HD.

PMID- 18638087
TI  - Interdialytic blood pressure obtained by ambulatory blood pressure measurement
      and left ventricular structure in hypertensive hemodialysis patients.
AB  - Unlike in subjects with normal renal function, the relationship between
      hypertension and cardiovascular morbidity and mortality in dialysis patients is
      still being debated. In order to clarify this issue, we performed 44-hour
      ambulatory blood pressure measurements (ABPM) during the interdialytic period in
      a group of 164 hypertensive patients, the blood pressure (BP) control based on
      conventional antihypertensive strategy previously, on chronic hemodialysis
      treatment in the Mediterranean region of Turkey. These results were then compared
      with their echocardiographic data. This is a cross-sectional analysis. The mean
      ABPM during 44 hours was close to the manually measured predialysis value, but
      there was a gradual increase in the ABPM values in the interdialytic period. When
      divided into a group with mild or no left ventricular hypertrophy (LVH) (45
      patients) and severe LVH (119 patients), the latter had significantly higher BP
      levels in all separate periods, while the difference in predialysis BP was not
      significant. Patients with severe LVH had larger left atrium and left ventricular
      diameters, and consumed more antihypertensive drugs. Systolic BP during the night
      before dialysis showed the strongest relation to LVH, but interdialytic weight
      gain was also independently related to LVH. Yet, 56% of the patients with
      systolic BP <135 had severe LVH. There is not only an association between BP and
      presence of LVH, but it is shown that volume expansion is also an important
      independent determinant of LVH. This may explain the difficulty in identifying
      hypertension as a cardiac risk factor in these patients.

PMID- 18638088
TI  - Vascular access for hemodialysis: experience of a team of nephrologists.
AB  - A survey conducted by Bonucchi et al. underlined the different types of doctors
      placing arteriovenous fistula (AVF) for hemodialysis in the United States and
      Europe (in particular Italy). In fact, nephrologists definitely prevail in Italy,
      where almost 48.8% of nephrologists place an AVF themselves or with the help of a
      vascular surgeon (26.4%). In Europe, only 35% do so, whereas 89% of AVF are
      performed by surgeons in the United States. In 98% of the cases occurring at our
      center, the AVF was placed and reviewed by the nephrologists. This paper reports
      surgery cases related to the period between January 1983 and September 2006. Over
      this time, 1386 operations for placing and reviewing vascular access were
      conducted. Among these, 47 (3.3%) were related to a cuffed central venous
      catheter (CVC); 1138 (80.2%) related to a distal AVF; 201 (10.6%) related to a
      proximal AVF; and 51 (3.6%) related to an arteriovenous graft (AVG). In addition,
      33 (2.3%) operations performed before January 1983 relating to AV Scribner shunts
      were included. Arteriovenous fistulas or AVGs were provided to our patients (only
      2.6% of them have a CVC), and AVF rescue operations were performed in the
      shortest possible time with advantages for the patient and his vascular access.

PMID- 18638089
TI  - Human platelet antigens polymorphisms and susceptibility of thrombosis in
      hemodialysis patients.
AB  - To investigate the association between the polymorphisms of human platelet
      antigen (HPA)-1,2,3,4,5 and susceptibility to develop thrombosis accident in
      arteriovenous fistula (AVF), genomic DNA of 112 hemodialysis (HD) patients and
      100 healthy blood donors were genotyped by PCR-SSP. The patients were classified
      into 2 groups: G1 included 54 HD patients presented at least one thrombotic
      episode on the level of the AVF, and G2 included 58 HD patients without any
      episode of thrombosis. The allelic frequencies of HPA-1, 2, 3, and 5 among
      patients and controls did not reveal significant differences. However, the HPA-4b
      allele was significantly more frequent in G1 than in controls or in G2 patients
      (23.1% vs. 11.5% and 0.9%, respectively), p<0.01 and p<0.001. The genotype
      distribution of HPA-4 polymorphism reveals that the HPA-4a4b genotype was more
      frequent in G1 patients (23/54: 42.6%) than in all HD patients (25/112: 22.3%) or
      in G2 patients (1/58: 1.72%) (p<0.001, odds ratio: 45.6). Among 24 HD patients
      with HPA-4a4b genotype, 23 (96%) developed at least 1 or more thrombotic episode
      on the level of their AVF. However, 30 patients (34.5%) among 87 HD patients with
      HPA-4a4a genotype presented thrombotic episode (p<0.001). These results reveal a
      significant association between HPA-4a4b and thrombosis, and it is likely that
      HPA polymorphisms could be useful markers for potential risk of thrombosis in
      hemodialysis.

PMID- 18638090
TI  - Factors affecting anemia management in hemodialysis patients: a single-center
      experience.
AB  - The difficulty maintaining hemoglobin (Hgb) within the targets recommended by
      KDOQI is widely recognized. While factors responsible for erythropoietin
      resistance have been widely studied, factors responsible for the marked
      fluctuations and the inability to maintain Hgb within the target range have only
      begun to be investigated. This study was a cross-sectional review of anemia
      management in hemodialysis patients. The purpose was to evaluate factors
      responsible for Hgb decreases of 0.5 or 1.0 g/dL and to determine the primary
      factors responsible for Hgb decreases below 11 g/dL. Hgb values and clinical
      events were extracted from patient management databases between January 1, 2005
      and November 30, 2006. Isolated events were defined as events that occurred at
      least 30 days after any previous event and had Hgb measurements within 2 weeks
      before and after the event. Increasing hospital length of stay and surgical
      access intervention were the most common events that resulted in a decrease in
      Hgb. The most common factor present in patients with Hgb decreases below 11 g/dL
      was the withholding of recombinant human erythropoietin (rHuEPO) within the
      preceding 2 months. This was the only explanation for the decrease in Hgb to <11
      g/dL in 38.5% of such events. The ability to maintain dialysis patients' Hgb in
      the target range is complicated by intervening acute events that require
      hospitalization or surgical access interventions. The withholding of rHuEPO
      appears to be a major factor in Hgb decreases below 11 g/dL.

PMID- 18638091
TI  - Effect of an ethanol/trisodium citrate hemodialysis catheter locking solution on
      isolates of Candida albicans.
AB  - We conducted an in vitro study to assess the effect of a 30% ethanol/4% trisodium
      citrate (TSC) catheter locking solution on isolates of Candida albicans. Twelve
      isolates obtained from human blood cultures were tested in control solutions
      composed of broth and normal saline, and a test solution of 30% ethanol, 4% TSC,
      and broth. Colony counts were determined for control and test solutions at
      baseline and after 1, 24, and 48 hours of exposure. After 48 hours, the remaining
      test solution was filtered through a sterile filter funnel and rinsed with 10 mL
      of sterile water. Filters were aseptically transferred to agar plates and
      incubated for 24 hours. Control solutions grew well over the incubation period,
      as expected. In contrast, no viable growth was observed in test solutions 1 hour
      after instillation of the ethanol/TSC locking solution, or throughout the 48-hour
      study duration. Additionally, filters from test solutions displayed no growth. We
      conclude that a 30% ethanol/4% TSC catheter locking solution eradicated all
      isolates of C. albicans within 1 hour of exposure in this in vitro study, and
      shows promise as a new hemodialysis catheter locking solution.

PMID- 18638092
TI  - Tissue plasminogen activator as a hemodialysis catheter locking solution.
AB  - Tunneled hemodialysis catheters require a "locking solution" between treatments
      to prevent catheter thrombosis. Heparin locks can be unsafe in patients with life
      threatening bleeding diathesis because of unintentional anticoagulation. This
      study was designed to define the hematologic consequences of using tissue
      plasminogen activator (t-PA) as an alternative locking solution after heparin
      free hemodialysis (HF-HD). Following HF-HD, t-PA 2 mg was instilled into each
      lumen of the dialysis catheter in 10 patients. Euglobulin clot lysis time (ECLT),
      fibrinogen, D-dimer, and fibrin degradation products were measured during the
      last hour of dialysis, and repeated 15 and 30 minutes after catheter locking.
      Dialysis catheter performance was reassessed at the time of the next
      hemodialysis. Fibrinogen, D-dimer, and fibrin degradation products were elevated
      at all time points, but did not change after t-PA. ECLT decreased significantly
      from baseline 15 minutes after catheter locking (217+/-64 vs. 132+/-75 min,
      p=0.016). ECLT values had returned to baseline (202+/-56 minutes) by 30 minutes.
      No episodes of bleeding or catheter thrombosis occurred, and catheter performance
      did not deteriorate. A 2 mg t-PA locking solution preserved dialysis catheter
      performance. ECLT decreased at 15 minutes, but normalized by 30 minutes, and did
      not enter the range in which bleeding would be likely. No clinical events were
      seen during this transient increase in systemic fibrinolysis.

PMID- 18638093
TI  - The interleukin-10 promoter genotype predicts diastolic dysfunction in
      maintenance hemodialysis patients.
AB  - Interleukin-10 (IL-10) predominantly acts as an anti-inflammatory factor.
      Polymorphisms in the IL-10 gene promoter determine quantitative cytokine
      production. Doppler echocardiography and tissue Doppler imaging (TDI) are
      superior to conventional echocardiography to evaluate diastolic dysfunction. The
      IL-10 gene promoter polymorphism at position (-1082) was studied for its
      association with conventional and Doppler echocardiographic and TDI parameters in
      112 hemodialysis (HD) patients. Blood pressure, serum C-reactive protein (CRP),
      and albumin levels were also examined for the association study. The genetic
      association study showed that among the HD patients, there was no difference in
      the prevalence of systolic and diastolic dysfunction between genotypes on
      conventional echocardiography. However, using Doppler echocardiography and TDI,
      high producers for the IL-10 -1082 promoter (-1082/GG) have higher E velocities,
      E/A values, lateral, and septal E' velocities and a lower isovolumic ventricular
      relaxation time than low (-1082/AA) and intermediate producers (-1082/GA).
      Significantly higher levels of serum CRP levels and lower plasma albumin levels
      were found in low and intermediate producers for the IL-10 -1082 promoter than
      high producers. The IL-10 genotype may balance the effects of inflammatory
      cytokines on the myocardium and may be a determinant of LV function in HD
      patients.

PMID- 18638094
TI  - Effects of parenteral iron on inflammation and the myocardium in hemodialysis
      patients.
AB  - Inflammation is a nontraditional cardiovascular risk factor in hemodialysis
      patients. This pilot study tested the hypothesis that intravenous iron adds to
      this inflammation by increasing oxidative stress. Secondly, we described the
      association between iron indices and myocardial structure and function. Thirteen
      hemodialysis patients from a teaching hospital were recruited for this
      descriptive study and divided into 3 groups according to their iron profile
      (high, low, and intermediate). Oxidative stress was determined in vivo by mass
      spectroscopy with measurement of malondialdehyde (MDA), hexanal, and nonenal.
      Cardiac magnetic resonance imaging and 2-dimensional echocardiography were used
      to study any structural or functional changes, respectively. A strong correlation
      was found between iron indices and oxidative stress (MDA and ferritin r=0.95;
      p<0.001; MDA and transferrin saturation r=0.80, p<0.01). Magnetic resonance
      imaging measurements showed a weak correlation with iron indices while no
      correlation was found between iron indices and echocardiographic measurements.
      Iron indices are positively correlated with functional oxidative stress. Larger
      studies are needed to determine the association between inflammation and
      structural or functional dysfunction of the myocardium.

PMID- 18638095
TI  - Central venous oxygen saturation and thoracic admittance during dialysis: new
      approaches to hemodynamic monitoring.
AB  - Intradialytic hypotension (IDH) is one of the most important short-term
      complications to hemodialysis (HD). Inadequate cardiac filling due to a reduction
      in the central blood volume is believed to be a major etiological factor. The aim
      of this study was to evaluate whether these pathophysiologic events are reflected
      in the central venous oxygen saturation (ScO(2)) and thoracic admittance (TA)
      during dialysis. Twenty ambulatory HD patients, 11 hypotension prone (HP) and 9
      hypotension resistant, with central vascular access, were monitored during 3 HD
      sessions each. ScO(2), TA, finger blood pressure (BP), and relative change in
      blood volume (DeltaBV) were measured and sampled continuously. The relative TA
      decrease and DeltaBV were both largest in the HP group (p<0.05 for both), whereas
      ScO(2) decreased only in HP patients (p<0.001). Baseline TA was lower in the HP
      group (p<0.01). Changes in ScO(2) and TA correlated much closer than did changes
      in ScO(2) and DeltaBV (r=0.43 and 0.18, respectively). Our results suggest that
      an intradialytic decrease in cardiac output, as reflected by a fall in ScO(2), is
      a common feature to HD patients prone to IDH. In patients using a central
      vascular access, ScO(2) and TA measurements may be more specific to the
      pathophysiologic events preceding IDH than DeltaBV-the current standard
      monitoring method.

PMID- 18638096
TI  - Hepatitis B and C in dialysis units in Iran: changing the epidemiology.
AB  - Hepatitis B (HBV) and C (HCV) viruses are the most important infections
      transmitted by the parenteral route in patients receiving maintenance dialysis.
      The prevalence varies markedly from country to country. The aim of this study is
      to review the efficacy of the strategies to reduce the incidence of these
      infections and the trend of results in Iran. As a routine, all hemodialysis
      patients in Iran have biannual blood samples for assessment of serum HBSAg, HBS
      Abs, and HCV Abs. The data are collected in the Ministry of Health. For
      statistical analysis, prevalence, and incidence were calculated. There is an
      increasing prevalence/incidence of end-stage renal disease (ESRD) in Iran, from
      238/49.9 pmp in 2000 to 357/63.8 pmp in 2006. The prevalence of positive HBSAg
      and HCV Abs decreased from 3.8% and 14.4% in 1999 to 2.6% and 4.5% in 2006,
      respectively. Regarding the genotype distribution in Iran, no one was found with
      genotype 2. On the subject of decreasing HBV infection, our next strategy should
      be mandatory vaccination in dialysis centers and in the pre-ESRD period.
      Concerning HCV infection prevention, 2 approaches may be recommended: the first
      is decrease of duration of the hemodialysis period by possible early
      transplantation of suitable patients. The next is a strictly enforced isolation
      policy for HCV-positive patients, which may play a role in limiting HCV
      transmission in HD units, and universal precaution in dialysis units should be
      under constant close surveillance.

PMID- 18638097
TI  - Decreased hemodialysis circuit pressures indicating postpump tubing kinks: a
      retrospective investigation of hemolysis in five patients.
AB  - The source of hemolysis during hemodialysis must be quickly identified to avoid
      life-threatening complications. At a single clinic, over a 10-day period in which
      550 treatments were performed, 5 case-patients were retrospectively identified
      for experiencing acute hemolysis (4 deaths) from an unknown origin. The
      investigation focused on the postpump arterial tubing as the pressure was not
      monitored in this region, and the segment was shorter than required and could
      kink if overly stressed at bend points (i.e., tubing support clips, dialyzer
      inlet). To determine whether the circuit pressures indicated kinked tubing, a
      relative comparison between each case-patient's recorded arterial (prepump) and
      venous circuit pressures throughout their adverse event treatment and their
      immediately preceding treatment was conducted. Treatment pressure-time traces
      showed that sustained, significant decreases (>25 mmHg) in both of the circuit
      pressures occurred only on the hemolytic event dates. While direct observations
      of kinked tubing were not reported, the circuit pressure decreases could only be
      explained by severe postpump tube kinking causing a decrease in the blood flow
      rate. While postpump obstructions and hemolysis can occur without causing
      noticeable changes to the prepump arterial and venous blood line pressures (due
      to the highly occlusive setting of the roller blood pump), recognizing sudden
      and/or sustained decreases in the circuit pressures during treatment may help to
      prevent adverse patient events. This analysis reinforces the importance of
      regularly checking the blood tubing set for kinks and for monitoring the circuit
      pressures for atypical trends within and between treatments.

PMID- 18638098
TI  - Functional differences in the growth hormone and insulin-like growth factor axis
      in cattle and pigs: implications for post-partum nutrition and reproduction.
AB  - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) control growth and
      lactation in cattle and swine. Insulin participates in the endocrinology of
      growth and lactation because insulin and GH are antagonistic in their actions.
      Dairy cows experience a period of negative energy balance during the first 4-8
      weeks post-partum. During this period, their somatotropic axis (comprised of GH,
      the GH receptor and IGF-I) becomes uncoupled and there is elevated GH and
      diminished IGF-I in the circulation. Blood insulin concentrations are low as
      well. Sows are different from dairy cows because their somatotropic axis remains
      coupled during lactation and both GH and IGF-I are elevated. Nonetheless, sows
      that become catabolic during lactation will have reduced IGF-I concentrations.
      Sows are inseminated after weaning so their metabolic state is different from
      post-partum beef and dairy cows that are inseminated when they are lactating.
      Dairy cows are fed ad libitum and naturally have low IGF-I during lactation. Sows
      have elevated IGF-I when they are well-fed. A threshold of IGF-I protein in
      follicular fluid may be met by local ovarian (paracrine/autocrine) and endocrine
      sources of IGF-I. Nutritionally induced changes in insulin and in liver IGF-I
      secretion that arise from perturbations of the somatotropic axis have a direct
      effect on the ovary through the endocrine actions of insulin and IGF-I. Sows and
      cows that are nutritionally compromised have low concentrations of insulin and
      IGF-I in their blood and this theoretically reduces ovarian responsiveness to
      gonadotropins. Although sows are inseminated after weaning, there appear to be
      carry-over effects of the previous lactation on the ovarian follicular
      populations that develop after the sow is weaned. Understanding the mechanisms
      through which metabolic hormones control ovarian function may lead to improved
      reproductive management of both pigs and cattle because lactation and post-partum
      reproduction are closely tied in both species.

PMID- 18638099
TI  - The manipulation of gametes and embryos in farm animals.
AB  - This paper summarizes the major advances in farm animal assisted reproduction in
      the last 20 years with particular attention to the contributions of the authors.
      A main emphasis is on the biology of the oocyte, including a description of
      methods for isolation of developing follicles and culture of the corresponding
      oocytes. Milestones that have led to optimization of procedures for maturation of
      fully grown oocytes, fertilization, intracytoplasmic sperm injection and embryo
      culture in sheep, cattle, pigs and horses are described. The current status of
      nuclear transfer, cloning and embryonic stem cell generation and culture is also
      summarized for all major farm animal species. It is concluded that the
      manipulation of early development in farm animals is of crucial importance for
      agricultural purposes and that reproductive biotechnologies in farm animals are
      expected to play an increasing role in the next decades due to the growing demand
      for agricultural products from the emerging economies worldwide. In the
      biomedical field large animals represent increasingly important research models
      especially in the stem cell field for creating genetically modified animals for
      specific purposes. Finally, the successful translation of large animal research
      in the applied context requires solid science, long-term resource commitment from
      involved institutions, and vision, dedication and entrepreneurial skills from the
      scientists involved.

PMID- 18638100
TI  - Towards ethically improved animal experimentation in the study of animal
      reproduction.
AB  - The ethics of animal-based research is a continuing area of debate, but ethical
      research protocols do not prevent scientific progress. In this paper, we argue
      that our current knowledge of the factors that affect reproductive processes
      provides researchers with a solid foundation upon which they can conduct more
      ethical research and simultaneously produce data of higher quality. We support
      this argument by showing how a deep understanding of the genetics, nutrition and
      temperament of our experimental animals can improve compliance with two of the '3
      Rs', reduction and refinement, simply by offering better control over the
      variance in our experimental model. The outcome is a better experimental design,
      on both ethical and scientific grounds.

PMID- 18638101
TI  - Endocrine disruptors and other food-contaminating environmental pollutants as
      risk factors in animal reproduction.
AB  - Pollutants of many chemical classes, derived primarily from anthropogenic
      activities, are ubiquitous in the environment, persistent, biologically available
      and can exert adverse effects on the reproductive and other, indirectly related,
      physiological systems. Food is generally considered to be the major route of
      animal exposure in vertebrate species but the relative contributions of other
      routes of exposure such as through lungs, gills or skin are not well studied and
      may be of importance for certain animal groups, depending on their immediate
      environment. Animals are particularly sensitive to exposure during developmental
      stages but the pattern of exposure to chemicals is likely to be different to that
      of adults. Quantification of the risk posed by the ingestion of pollutants in
      food is complex and depends on many factors including species, diet composition,
      duration of exposure to the food, efficiency of pollutant absorption, subsequent
      metabolism, sensitivity of target organs and stage of development. While the
      effects of high doses of single chemicals are proven, dietary exposure to
      pollutants generally involves prolonged, low-level exposure to a large number of
      compounds, each of which has different chemical characteristics, exerts different
      biological effects and is present at varying concentrations. Thus, while exposure
      to pollutants through feed is undoubtedly a significant risk factor for many
      species and may be the most important one for many terrestrial vertebrates, other
      routes of exposure may be more important in other groups.

PMID- 18638102
TI  - Long chain fatty acids of diet as factors influencing reproduction in cattle.
AB  - Cattle are fed moderate amounts of long chain fatty acids (FA) with the objective
      to enhance lactation and growth; however, recent interest on lipid feeding to
      cows has focused on reproduction, immunity and health. Increasing the caloric
      density of the ration by fat feeding has generally improved measures of cow
      reproduction, but when milk yield and body weight losses were increased by fat
      supplementation, positive effects on reproduction were not always observed.
      Feeding fat has influenced reproduction by altering the size of the dominant
      follicle, hastening the interval to first postpartum ovulation in beef cows,
      increasing progesterone concentrations during the luteal phase of the oestrous
      cycle, modulating uterine prostaglandin (PG) synthesis, and improving oocyte and
      embryo quality and developmental competence. Some of these effects were altered
      by the type of FA fed. The polyunsaturated FA of the n-6 and n-3 families seem to
      have the most remarkable effects on reproductive responses of cattle, but it is
      not completely clear whether these effects are mediated only by them or by other
      potential intermediates produced during rumen biohydrogenation. Generally,
      feeding fat sources rich in n-6 FA during late gestation and early lactation
      enhanced follicle growth, uterine PG secretion, embryo quality and pregnancy in
      cows. Similarly, feeding n-3 FA during lactation suppressed uterine PG release,
      and improved embryo quality and maintenance of pregnancy. Future research ought
      to focus on methods to improve the delivery of specific FA and adequately powered
      studies should be designed to critically evaluate their effects on establishment
      and maintenance of pregnancy in cattle.

PMID- 18638103
TI  - Seasonality of reproduction in mammals: intimate regulatory mechanisms and
      practical implications.
AB  - Farm mammals generally express seasonal variations in their production traits,
      thus inducing changing availability of fresh derived animal products (meat, milk
      and cheese) or performances (horses). This is due to a more or less marked
      seasonal birth distribution in sheep and goats, in horses but not cattle. Birth
      peak occurs at the end of winter-early spring, the most favourable period for the
      progeny to survive. Most species show seasonal variations in their ovulation
      frequency (presence or absence of ovulation), spermatogenic activity (from
      moderate decrease to complete absence of sperm production), gamete quality
      (variations in fertilization rates and embryo survival), and also sexual
      behaviour. The intimate mechanism involved is a complex combination of endogenous
      circannual rhythm driven and synchronized by light and melatonin. Profound and
      long-term neuroendocrine changes involving different neuromediator systems were
      described to play a role in these processes. In most species artificial
      photoperiodic treatments consisting of extra-light during natural short days (in
      sheep and goats and mares) or melatonin during long days (in sheep and goats) are
      extensively used to either adjust the breeding season to animal producer needs
      and/or to completely overcome seasonal variations of sperm production in
      artificial insemination centres. Pure light treatments (without melatonin),
      especially when applied in open barns, could be considered as non-invasive ones
      which fully respect animal welfare. Genetic selection could be one of the future
      ways to decrease seasonality in sheep and goats.

PMID- 18638104
TI  - Mechanisms for dominant follicle selection in monovulatory species: a comparison
      of morphological, endocrine and intraovarian events in cows, mares and women.
AB  - The selection of a single ovarian follicle for further differentiation and
      finally ovulation is a shared phenomenon in monovulatory species from different
      phylogenetic classes. The commonality of dominant follicle (DF) development leads
      us to hypothesize that mechanisms for DF selection are conserved. This review
      highlights similarities and differences in follicular wave growth between cows,
      mares and women, addresses the commonality of the transient rises in FSH
      concentrations, and discusses the follicular secretions oestradiol and inhibin
      with their regulatory roles for FSH. In all three species, rising FSH
      concentrations induce the emergence of a follicle wave and cohort attrition
      occurs during declining FSH concentrations, culminating in DF selection. Cohort
      secretions are initially responsible for declining FSH, which is subsequently
      suppressed by the selected DF lowering it below the threshold of FSH requirements
      of all other cohort follicles. The DF acquires relative FSH-independence in order
      to continue growth and differentiation during low (cow, mare) or further
      declining FSH concentrations (women), and thus may be the one cohort follicle
      with the lowest FSH requirement due to enhanced FSH signalling. In all three
      monovulatory species a transition from FSH- to LH-dependence is postulated as the
      mechanism for the continued development of the selected DF. In addition, FSH and
      IGF enhance each other's ability to stimulate follicle cell function and access
      of IGF-I and -II to the type 1 receptor is regulated by IGF binding proteins that
      are in turn regulated by specific proteases; all of which have been ascribed a
      role in DF development. No fundamental differences in DF selection mechanisms
      have been identified between the different species studied. Thus functional
      studies of the selection of DFs in cattle and mares are also valuable for
      identifying genes and pathways regulating DF development in women.

PMID- 18638105
TI  - Regulation of luteal function and corpus luteum regression in cows: hormonal
      control, immune mechanisms and intercellular communication.
AB  - The main function of the corpus luteum (CL) is production of progesterone (P4).
      Adequate luteal function to secrete P4 is crucial for determining the
      physiological duration of the oestrous cycle and for achieving a successful
      pregnancy. The bovine CL grows very fast and regresses within a few days at
      luteolysis. Mechanisms controlling development and secretory function of the
      bovine CL may involve many factors that are produced both within and outside the
      CL. Some of these regulators seem to be prostaglandins (PGs), oxytocin, growth
      and adrenergic factors. Moreover, there is evidence that P4 acts within the CL as
      an autocrine or paracrine regulator. Each of these factors may act on the CL
      independently or may modify the actions of others. Although uterine PGF(2 alpha)
      is known to be a principal luteolytic factor, its direct action on the CL is
      mediated by local factors: cytokines, endothelin-1, nitric oxide. The changes in
      ovarian blood flow have also been suggested to have some role in regulation of CL
      development, maintenance and regression.

PMID- 18638106
TI  - Captive breeding of cheetahs in South Africa--30 years of data from the de Wildt
      Cheetah and Wildlife Centre.
AB  - The de Wildt Cheetah and Wildlife Centre was established in 1971 and the first
      cheetah cubs were born in 1975. During the period 1975-2005, 242 litters were
      born with a total of 785 cubs. Mean cub survival from 1 to 12 months and greater
      than 12 months of age was 71.3 and 66.2%, respectively. The majority of losses
      (84.9%) occurred during the first month postpartum whereas only 15.1% deaths took
      place between 1 and 12 months of age. Females were first bred at an age of
      approximately 3 years, reached maximum reproductive age at 6-8 years, where after
      fertility declined. Males reached peak reproduction at 6 and maintained this for
      up to 12 years of age. Male fertility was best correlated with sperm morphology.
      During recent years, for practical purposes, males were allocated to 'good'
      (>or=70% normal), 'fair' (40-70% normal) and 'poor' (<40% normal) categories
      according to sperm morphology count. The breeding males were selected from the
      good (preferably) and fair categories but poor category males were also used at
      times. Average litter sizes for 'good', 'fair' and 'poor' males were 3.44 (n =
      21), 3.14 (n = 18) and 2.28 (n = 18), respectively. In females the heritability
      for litter size was high at 0.5848 (532 progeny, 1975-2007) and the maternal
      heritability for cub mortality was estimated to be 0.596. The data from the de
      Wildt Cheetah and Wildlife Centre and two other centres in the world (Kapama and
      Wassenaar) demonstrate that cheetah can be bred successfully in captivity.

PMID- 18638107
TI  - Non-invasive monitoring of hormones: a tool to improve reproduction in captive
      breeding of the Eurasian lynx.
AB  - The survival of many critical endangered mammal species is often depending on
      successful captive breeding programmes which include the future option of
      reintroduction to the wild. Breeding in captivity also demands the application of
      modern assisted reproductive techniques to ensure maximal biodiversity, but
      knowledge on reproductive physiology is often limited. Therefore, non-invasive
      monitoring of urinary and faecal hormones has become an important tool for
      reproductive management. To exemplify the importance of non-invasive hormone
      monitoring, we choose the Eurasian lynx as a model for the world's most
      endangered felid species, the Iberian lynx. We analysed faecal samples of
      pregnant and pseudo-pregnant female Eurasian lynxes during a 3-year study period.
      Compared to pre-mating levels faecal progesterone metabolite profiles revealed a
      tendency towards higher levels in pregnant and pseudo-pregnant females with no
      difference between both categories. Oestrogen levels raised in both pregnant and
      pseudo-pregnant females with a tendency to be more elevated and prolonged in
      pregnant females. Surprisingly both E2 and P4 metabolites were highly correlated
      (r(2) =0.8131, p < 0.0001) showing a postpartum increase both in pregnant and
      pseudo-pregnant females. The results from the Eurasian lynx revealed that the
      measurement of faecal progesterone metabolites led to profiles dissimilar to
      profiles shown in other felid species, but similar to those from faecal gestagen
      metabolite analysis in the Iberian lynx. To identify faecal gestagen and
      oestrogen metabolites a radio-metabolism study was performed. Using the
      progesterone immunoassay two major progesterone metabolites were detected
      demonstrating that the assay indeed tracks the relevant metabolites. The
      oestrogen assay measured authentic 17beta-oestradiol and oestrone, and their
      conjugates. The analysis of the faecal metabolite composition in samples from
      early and late pregnancy and lactation particularly revealed a distinct shift in
      the relation between 17beta-oestradiol and oestrone that changed in favour of
      oestrone. This might indicate different hormone sources during and after
      pregnancy (corpus luteum, placenta). We hypothesize, that placental steroid
      analysis in combination with other highly sophisticated analytical techniques,
      like liquid chromatography mass spectrometry or urinary relaxin analysis may led
      to analytical options to confirm pregnancy and to differentiate this from pseudo
      pregnancy in lynx species.

PMID- 18638108
TI  - Reproductive biotechnology and gene mapping: tools for conserving rare breeds of
      livestock.
AB  - Today's livestock diversity originated from the wild ancestor species and was
      subsequently shaped through the processes of mutation, genetic drift, and natural
      and human selection. Only a subset of the diversity present in the ancestral
      species survives in the domestic counterparts. A 2007 report released by UN Food
      and Agriculture Organization 'The State of the World's Animal Genetic Resources',
      compiled from surveys conducted in 169 countries, found that nearly 70% of the
      world's remaining livestock breeds live in developing countries. The UN report
      was presented to more than 300 policy makers, scientists, breeders, and livestock
      keepers at the First International Technical Conference on Animal Genetic
      Resources, held in September 2007 in Interlaken, Switzerland. The conference aims
      were to adopt a global plan of action for conserving animal genetic resources as
      its main outcome. In this paper, the current and potential contributions of
      reproductive and molecular biotechnology are considered as tools of conserving
      rare breeds of livestock.

PMID- 18638109
TI  - Genetic improvement of dairy cow reproductive performance.
AB  - The welfare of cow along with profitability in production are important issues in
      sustainable animal breeding programmes. Along with an intense/intensive selection
      for increased milk yield, reproductive performance has declined in many
      countries, in part due to an unfavourable genetic relationship. The largely
      unchanged genetic trend in female fertility and calving traits for Scandinavian
      Red breeds shows that it is possible to avoid deterioration in these traits if
      they are properly considered in the breeding programme. Today's breeding is
      international with a global selection and extensive use of the best bulls. The
      Nordic countries have traditionally recorded and performed genetic evaluation for
      a broad range of functional traits including reproduction. In recent years many
      other countries have also implemented genetic evaluation for these traits. Thus,
      the relative emphasis of dairy cattle breeding objectives has gradually shifted
      from production to functional traits such as reproduction. Improved ways of
      recording traits, e.g. physiological measures, early indicator traits, assisted
      reproductive techniques and increased knowledge of genes and their regulation may
      improve the genetic selection strategies and have large impact on present and
      future genetic evaluation programmes. Extensive data bases with phenotypic
      recordings of traits for individuals and their pedigree are a prerequisite.
      Quantitative trait loci have been associated to the reproductive complex. Most
      important traits, including reproduction traits are regulated by a multitude of
      genes and environmental factors in a complex relationship, however. Genomic
      selection might therefore be important in future breeding programmes. Information
      on single nucleotide polymorphism has already been introduced in the selection
      programmes of some countries.

PMID- 18638110
TI  - Nutrient prioritization in dairy cows early postpartum: mismatch between
      metabolism and fertility?
AB  - For several decades, researchers worldwide report a decrease in fertility in high
      yielding dairy cows, most probably based on conflicting metabolic and
      reproductive needs. The dairy herd manager's success at improving milk production
      has been accompanied by a negative trend for the most visible reproductive
      parameters such as calving intervals, number of days open and number of
      inseminations needed per pregnancy. In parallel, many research groups studied the
      metabolic and endocrine factors that influence follicular growth and the
      developmental competence of oocytes and embryos. In the past, herd managers and
      reproductive biologists each tried to tackle the same problems with limited
      consultation. More recently, the situation has improved significantly and
      theriogenologists, nutritionists and veterinarians now conduct research in
      multidisciplinary teams. This review paper starts in a general way by discussing
      nutrient prioritization towards the udder to guarantee milk production and by
      describing interactions between the somatotropic and gonadotropic axis. It then
      focuses on the consequences of the negative energy balance on follicular growth
      and environment, oocyte and embryo quality, not only by summarizing the currently
      accepted hypotheses but also based on clear scientific evidence at the follicular
      level. All this, with one question in mind: is there a mismatch between
      metabolism and fertility and what can the dairy manager learn from research to
      tackle the problem of reduced fertility?

PMID- 18638111
TI  - Corpus luteum-endometrium-embryo interactions in the dairy cow: underlying
      mechanisms and clinical relevance.
AB  - Conception rates of dairy cows are currently declining at an estimated 1% every
      year. Approximately, 35% of embryos fail to prevent luteolysis during the first
      three weeks of gestation. Interactions between the corpus luteum, endometrium and
      embryo are critical to the successful establishment of pregnancy and inadequacies
      will result in the mortality of the embryo. For example, as little as a one day
      delay in the post-ovulatory rise of progesterone has serious consequences for
      embryo development and survival. Recently, we found that LH support, degree of
      vascularization and luteal cell steroidogenic capacity were not the major factors
      responsible for this luteal inadequacy, but are nevertheless essential for luteal
      development and function. Progesterone acting on its receptor in the endometrium
      stimulates the production of endometrial secretions on which the free-living
      embryo is dependent. However, their exact composition and effects of inadequate
      progesterone remains to be determined. The embryo is recognized through its
      secretion of interferon tau (IFNT), which suppresses luteolytic pulses of
      prostaglandin F(2 alpha). In the cow, it is most likely that IFNT inhibits
      oxytocin receptor up-regulation directly and does not require the prior
      inhibition of oestrogen receptor alpha (ESR1). Unravelling the precise luteal
      endometrium and embryo interactions is essential for us to understand pregnancy
      establishment and development of strategies to reverse the declining fertility of
      dairy cows.

PMID- 18638112
TI  - Improved detection of reproductive status in dairy cows using milk progesterone
      measurements.
AB  - This study tested a model for predicting reproductive status from in-line milk
      progesterone ;measurements. The model is that of Friggens and Chagunda
      [Theriogenology 64 (2005) 155]. Milk progesterone measurements (n = 55 036)
      representing 578 lactations from 380 cows were used to test the model. Two types
      of known oestrus were identified: (1) confirmed oestrus (at which insemination
      resulted in a confirmed pregnancy, n = 121) and (2) ratified oestrus (where the
      shape of the progesterone profile matched that of the average progesterone
      profile of a confirmed oestrus, n = 679). The model detected 99.2% of the
      confirmed oestruses. This included a number of cases (n = 16) where the smoothed
      progesterone did not decrease below 4 ng/ml. These cows had significantly greater
      concentrations of progesterone, both minimum and average, suggesting that between
      cow variation exists in the absolute level of the progesterone profile. Using
      ratified oestruses, model sensitivity was 93.3% and specificity was 93.7% for
      detection of oestrus. Examination of false positives showed that they were
      largely associated with low concentrations of progesterone, fluctuating around
      the 4 ng/ml threshold. The distribution of time from insemination until the model
      detected pregnancy failure had a median of 22 days post-insemination. In this
      test, the model was run using limited inputs, the potential benefits of including
      additional non-progesterone information were not evaluated. Despite this, the
      model performed at least as well as other oestrus detection systems.

PMID- 18638113
TI  - Genetic aspects of reproduction in sheep.
AB  - Maintenance of high levels of realized fertility (defined as the percentage of
      ewes that lamb) and appropriate levels of fecundity are critical for efficient
      sheep production. The optimal level of fecundity in most situations is well below
      the maximum attainable level and can be targeted by combining selection among and
      within breeds with use of an expanding array of single-gene mutations affecting
      ovulation rate and litter size. The heritability of litter size is approximately
      0.10, allowing changes of up to 2%/year from simple mass selection. Mutations in
      several genes associated with the transforming growth factor beta superfamily
      (BMPRIB, GDF9 and sex-linked BMP15) can increase ovulation rates by 0.7-1.5 ova
      in heterozygous ewes. However, ewes that are homozygous for BMP15 or GDF9
      mutations are sterile, so use of these mutations requires carefully structured
      breeding programmes. Improvements in fertility may be critical for autumn lambing
      or programmes that aspire to lamb throughout the year. Selection to improve
      fertility in spring matings has been successful; selected adult ewes have lambing
      rates of 80-85% in October and early November. The selected ewes have a
      dramatically reduced seasonal anestrus, and many ewes continue to cycle during
      spring and summer. Major genes affecting seasonal breeding have not been
      identified in sheep. Polymorphisms in the melatonin receptor 1a gene appear to be
      associated with seasonal breeding in some, but not all breeds. However,
      functional genomic studies of genes associated with circadian and circannual
      rhythms have potential to reveal additional candidate genes involved in seasonal
      breeding.

PMID- 18638114
TI  - The importance of interactions among nutrition, seasonality and socio-sexual
      factors in the development of hormone-free methods for controlling fertility.
AB  - Around the world, consumers are demanding animal products that are produced to
      agreed standards for human health, environmental management and animal welfare.
      This has led to the development in Australia of the concept of 'clean, green and
      ethical' (CGE) animal production based on the manipulation of nutrition ('focus
      feeding') and the application of phenomena, such as the 'male effect', to provide
      'natural' methods for managing small ruminant production systems. With respect to
      the management of fertility, CGE involves utilization of the inherited responses
      of animals to environmental factors to manipulate their reproductive processes.
      The successful development and implementation of this new generation of
      management tools depends on a thorough yet holistic understanding of the
      interactions among environmental factors and the ways these interactions affect
      reproductive physiology and behaviour of the animal. For sheep and goats, a
      central aspect of CGE management is the way in which ovarian function is affected
      by three major factors (nutrition, photoperiod and socio-sexual signals) and by
      interactions among them. Nutrition can exert two profound yet contrasting types
      of effect on ovarian activity: (i) the complete inhibition of reproduction by
      undernutrition through the hypothalamic mechanism that controls ovulation and
      (ii) the enhancement of fecundity by nutritional supplementation, through a
      direct ovarian mechanism, in females that are already ovulating. A similarly
      profound control over ovarian function in female sheep and goats is exerted by
      the well-known endocrine responses to photoperiod (seasonality) and to male socio
      sexual signals. The 'male effect' already has a long history as a valuable
      technique for inducing a synchronized fertile ovulation during seasonal and post
      partum anoestrus in sheep and goats. Importantly, experimentation has shown that
      these three major environmental factors interact, synergistically and
      antagonistically, but the precise nature of these interactions and their
      significance to reproductive outcomes are not well understood. Most research to
      date has been with small ruminants but CGE principles can be applied to any
      species in a managed environment. For example, a male effect has been reported
      for lactating cattle and, in the horse, the pattern of seasonality of oestrus can
      be altered by nutrition. Well-fed mares have a longer breeding season and some
      animals become non-seasonal. Similar observations have been reported for sheep
      and goats. By working towards a holistic perspective of the physiology,
      nutrition, genetics and behaviour of our animals, we will be able to formulate
      ways to manipulate the animals' environment that will improve management,
      productivity and profitability and, simultaneously, promote a CGE industry.

PMID- 18638115
TI  - Developmental capabilities of embryos produced in vitro from prepubertal lamb
      oocytes.
AB  - Breeding from prepubertal females, known as juvenile in vitro embryo transfer
      (JIVET), reduces the generation interval and increases the rate of genetic gain
      in animal breeding programs. While the birth of the first lambs from prepubertal
      ewes occurred nearly 30 years ago; and there is considerable interest in the
      commercialization of this technology, its efficiency remains too low. The advent
      of in vitro production (IVP) of embryo resulted in the more widespread use of
      JIVET. Morphologic and metabolic differences coupled with reduced in vitro and in
      vivo development of oocytes derived from prepubertal animals have been reported.
      Research has been undertaken to optimize donor selection and hormone stimulation
      methods in an attempt to reduce the variability and increase the proportion of
      donors responding to hormone stimulation and increase oocyte developmental
      competence. Yet, this variation persists and the development of oocytes and
      embryos from prepubertal animals remains reduced when compared with adults.
      Recent improvements to JIVET, resulting from a modified hormone stimulation
      regime, have eliminated the failure of donors to respond to hormone stimulation,
      and increased both the number and developmental competence of oocytes harvested
      from very young prepubertal lambs. This increased efficiency has facilitated the
      incorporation of other reproductive technologies such as sperm sexing with JIVET,
      resulting in the birth of lambs of a pre-determined sex from prepubertal lambs.
      Increased rates of genetic gain in sheep breeding programs can be achieved by
      combining sexed sperm with oocytes obtained from lambs as young as 3-4 weeks of
      age. Continued increases in the efficiency of JIVET resulting from further
      improvements to hormone stimulation regimes and an increased understanding of the
      differences between oocytes from adult and prepubertal animals will result in the
      commercialization of this technology.

PMID- 18638116
TI  - Updates on reproductive physiology, genital diseases and artificial insemination
      in the domestic cat.
AB  - Reproduction in the domestic cat is characterized by large individual variations
      in the female oestrous cycle and in male semen quality. The female cat
      reproduction is strongly influenced by season, and new data suggest that it is
      possible that season also affects male fertility. Repeated periods of oestrus and
      spontaneous ovulation may lead to degenerative endometrial changes causing
      infertility. For artificial insemination (AI), induction of ovulation is
      necessary in the absence of the mating stimuli. The large variation in the
      relationship between follicular growth and timing of expression of oestrus
      complicates, however, timing of ovulation induction. Stress may lead to
      progesterone secretion by the adrenal glands and possibly have a negative impact
      on early pregnancy. The large individual variation in semen quality makes
      fertility evaluation and feline semen conservation a challenge. For AI, the semen
      can be deposited in the cranial vagina, the uterus or in the uterine tubes.
      Intrauterine insemination results in higher pregnancy rates than intravaginal but
      is more complicated. Surgical intrauterine or intratubal insemination has
      resulted in the birth of kittens, but is an invasive procedure that is not
      allowed in all countries. Transcervical intrauterine insemination with frozen
      thawed semen has, however, recently resulted in the birth of kittens.

PMID- 18638117
TI  - Reproduction of the female ferret (Mustela putorius furo).
AB  - The domestic ferret is a seasonally polyoestrous species. Females reach puberty
      at the age of 8-12 months. Females exhibit a constant oestrus between late March
      and early August if they are not bred. Increasing tumescence in the pink-coloured
      vulva is a sign of pro-oestrus. Oestrus can persist for up to 5 months, but once
      ovulation is induced, either pregnancy or pseudopregnancy ensues. Follicular
      development and atresia overlap in such a manner that there is a recent cohort of
      follicles available for ovulation whenever copulation might occur. Copulation may
      last from 15 min to 3 h, the average being 1 h. Ovulation is induced by pressure
      on the cervix associated with copulation. After sufficient LH release, the pre
      ovulatory follicles mature and an average of 12 oocytes (5-13) per female are
      ovulated 30-40 h after copulation into the ovarian bursa. The ferret oocytes are
      most capable of being fertilized up to 12 h after ovulation, i.e. 42-52 h after
      copulation. Ferret oocytes ovulate at the metaphase of the second meiotic
      division (MII) embedded in three layers of corona radiata cells. Embryos enter
      the uterus over a period of several days starting on day 5 after mating. Between
      days 12 and 13 after mating, the embryos have become implanted in the
      endometrium. Implantation in the ferret is central with rapid invasion of the
      uterine epithelium by the trophoblast over a broad area that eventually becomes a
      zonary band of endotheliochorial placenta. Gestation length is 41 days (39-42
      days). The domestic ferret gives birth to an average of eight kits (1-18 kits),
      which weigh 6-12 g at birth.

PMID- 18638118
TI  - Physiology of the canine anoestrus and methods for manipulation of its length.
AB  - Progression from early to late anoestrus is characterized by the appearance of a
      larger number of gonadotrophin-releasing hormone (GnRH) pulses with a higher
      amplitude, an increase in the sensitivity of the pituitary to GnRH, an increase
      in ovarian responsiveness to gonadotrophins, and an increase in basal plasma
      follicle-stimulating hormone (FSH) concentration. A period of increased
      luteinizing hormone (LH) pulsatility has been observed shortly before the onset
      of pro-oestrus. Apart from these changes in the hypothalamus-pituitary-ovary
      axis, the initiation of a new follicular phase in the bitch is also stimulated by
      dopaminergic influences other than the accompanying plasma prolactin decrease.
      Metergoline, a drug which in a low dosage lowers the plasma prolactin
      concentration via a serotonin-antagonistic pathway, does not shorten the
      anoestrus; while bromocriptine, in a dosage insufficient to cause a decrease in
      the plasma prolactin concentration, does prematurely induce a follicular phase.
      These observations indicate that it is not the decrease in the plasma prolactin
      concentration, but another dopamine-agonistic influence that plays a crucial role
      in the transition to a new follicular phase. The dopamine-agonist induced oestrus
      is associated with a rapid rise in the basal plasma FSH concentration, similar to
      what is observed during the physiological late anoestrus. Administration of GnRH,
      eCG and oestrogens may also be used to induce oestrus but with variable results.
      Oestrus can be prevented surgically or medically, for which purpose progestagens
      are the most important drugs. The mechanism is still unclear, although it has
      been demonstrated that with continuing medroxyprogesterone acetate (MPA)
      treatment the FSH response to GnRH stimulation decreases and changes occur in the
      pulsatile release of the gonadotrophins. In general, LH pulses coincide with a
      FSH pulse, but during MPA treatment, LH pulses were observed while there was such
      a small increase in FSH that it was not recognized as significant FSH pulse.

PMID- 18638119
TI  - The ethics and role of AI with fresh and frozen semen in dogs.
AB  - The use of artificial insemination (AI) with fresh semen has resulted in many
      benefits for the management of dog breeding, but there are disadvantages that can
      sometimes be overlooked. Furthermore, poorer quality semen arising as a result of
      cryopreservation necessitates uterine insemination, which raises the potential
      for surgical insemination. A number of significant ethical concerns have been
      raised by key stakeholders (such as The Kennel Club and the Royal College of
      Veterinary Surgeons) about AI per se, but particularly about the use of surgical
      insemination. This paper discusses the technological development of AI and
      explores a number of the ethical issues raised by its application to dog
      breeding. An Ethical Matrix method is used to map the potential ethical issues
      for key interest groups, namely dogs, breeders, owners, veterinarians and wider
      society. There are national variations in the way in which institutions have
      evaluated potential ethical impacts, and this is reflected in the different
      regulatory frameworks governing the use of AI in dogs. In order to facilitate
      decision-making and reduce some of the ethical risks associated with this
      technology, the veterinary research community could take several proactive steps
      including: (i) clarifying clinical decision-making processes, (ii) enhancing
      informed choice among clients and (iii) increasing the knowledge-base of
      potential impacts of AI.

PMID- 18638120
TI  - Basic aspects of the control of GnRH and LH secretions by kisspeptin: potential
      applications for better control of fertility in females.
AB  - The neuronal control of fertility and sterility has been a subject of research
      for years. However, nowadays, in spite of considerable literature about GnRH
      during the last few decades, the precise cellular and molecular mechanisms
      whereby gonadal steroids and other peripheral signals converge in the brain to
      achieve the fine regulation of GnRH secretion remains partially unknown. In this
      scenario, a major breakthrough in our understanding of the neuronal signals
      governing reproduction took place in 2003 with the discovery of
      metastin/kisspeptin as a major player in the control of GnRH secretion. This
      molecule, first described as having a crucial role in triggering the onset of
      puberty, is involved in all phases of reproductive life and hence has attracted
      the interest of many reproductive neuroendocrinologists. Administered either
      centrally or peripherally, kisspeptin strongly induces the secretion of
      gonadotropin in many species, mainly through stimulation of GnRH secretion.
      Kisspeptin cells involved in the control of GnRH secretion are located in two
      regions of the brain: the preoptic area and the arcuate nucleus. Carrying
      oestradiol receptor alpha, kisspeptin cells of these regions appear to be the
      main integration centres for the expression of both the positive and negative
      feedback of steroid on GnRH secretion. More recently, this molecule has been
      shown to be able to synchronize preovulatory surges in cyclic ewes and cause
      ovulation in seasonally acyclic ewes. This review summarizes the most relevant
      aspects of the role of kisspeptin in GnRH/LH release and the potential
      application of this molecule in new strategies for controlling female fertility.

PMID- 18638121
TI  - Controlling animal populations using anti-fertility vaccines.
AB  - The goal for fertility control of animal populations is the development of a
      safe, economical and effective contraceptive. One offshoot of the development of
      this technology is the acquisition of multiple therapeutic strategies for
      diseases, such as immunotherapy probes for cancer. In the long run, successful
      population control requires multifactorial strategies. One component of
      population control is immunocontraception. Development of effective antigens for
      immunocontraceptive vaccines has been remarkable and has greatly advanced our
      understanding of the molecular mechanisms of fertilization. The chasm between the
      discovery of an antigen in the laboratory, to the implementation of an effective
      field program, is immense. The zona pellucida (ZP) immunocontraceptive that has
      been most extensively evaluated as a fertility vaccine antigen and the porcine ZP
      has received particular attention. The long-term goal of population control would
      be the use of a synthetic vaccine, e.g. the ZP, tailored to a target species. In
      the future, if populations' levels are to be controlled by fertility vaccines, we
      should consider that the vaccinated animals could receive other health protective
      agents at the same time. For example, if a species were immunocontracepted, then
      they could be simultaneously vaccinated against habitat diseases such as rabies
      (Plumb et al., Rev Sci Tech, 26, 2007, 229).

PMID- 18638122
TI  - The expanding role of recombinant gonadotropins in assisted reproduction.
AB  - Using recombinant gonadotropins for assisted reproduction of domestic species is
      still in its infancy. Yet, the purity, potency and pathogen-free nature of
      recombinant gonadotropins make them attractive alternatives to tissue-derived
      gonadotropic agents. In this study, the authors summarize the work to date using
      recombinant gonadotropins to enhance the - fertility of domestic animals and they
      discussed their recent studies examining the biopotency of single chain analogues
      of human gonadotropins. In these studies, single chain analogues of follicle
      stimulating hormone (Fc alpha), chorionic gonadotropin (CG beta alpha) or a
      gonadotropin construct with dual activity (FcCG beta alpha) were administered to
      sheep pre-treated with antisera directed against GnRH. Ovulation was induced 3
      days after analogue administration using hCG (1000 IU, iv). Although Fc alpha or
      CG beta alpha alone induced only modest oestradiol production during the pre-hCG
      period, serum concentrations of oestradiol were markedly increased (p < 0.05) 3
      days after administration of FcCG beta alpha or the Fc alpha + CG beta alpha
      combination. Final ovarian weight was significantly increased (p < 0.05) in
      animals receiving Fc alpha, Fc alpha + CG beta alpha or FcCG beta alpha.
      Collectively, these observations demonstrate that the single chain analogues of
      the human gonadotropins are active in sheep.

PMID- 18638123
TI  - Recent progress in embryonic stem cell research and its application in domestic
      species.
AB  - Many reports described cell lines derived in domestic species, which presented
      several important features typical of embryonic stem cells (ESCs). Such features
      unfortunately did not include the capacity to generate germ-line chimeras,
      therefore limiting the possibility to use these cells as tools for the genetic
      manipulation. However, farm animal ESCs may still be useful for the generation of
      transgenic animals as usually have a self-renewal capacity more prolonged than
      normal primary cultures thus increasing the possibility to transform and select
      cells to be used as nucleus donors in cloning procedures. Farm animal ESCs may
      also be an excellent experimental model in pre-clinical trials, assessing the
      feasibility of cell therapy because of the close morphological and physiological
      resemblance to humans of species like the pig. However, the persistent lack of
      standard methods for the derivation, maintenance and characterization of ESCs in
      domestic species stimulated the search for alternatives. Embryonic germ cells may
      represent such an alternative. Indeed, these cells showed a higher plasticity
      than ESCs as contributed to embryonic development forming chimeric newborns but,
      as for ESCs, standardization is still far away and efficiency is very low. Recent
      results indicated spermatogonial stem cells as possible tools for germ-line
      genetic modifications with some proof of principle results already achieved. But,
      a real break through could arrive from the multipotent germ-line stem cells,
      virtually equivalent to ESC, derived from newborn and adult mouse testis.

PMID- 18638124
TI  - Reproduction in domestic buffalo.
AB  - The domestic buffalo is an indispensable livestock resource to millions of
      smallholder farmers in developing countries, particularly in Asia. Although its
      reproductive biology is basically similar to that of cattle, there are important
      differences and unique characteristics that need to be considered in order to
      apply modern reproductive technologies to improve its productivity. Under most
      smallholder production systems, the reproductive efficiency of buffalo is
      compromised by factors related to climate, management, nutrition and diseases.
      However, when managed and fed properly, buffalo can have good fertility and
      provide milk, calves and draught power over a long productive life. The basic
      technical problems associated with artificial insemination in buffalo were
      largely overcome two decades ago, but the technology has not had the expected
      impact in some developing countries, because largely of infrastructural and
      logistic problems. Approaches involving the use of hormones for treating
      anoestrus and for synchronizing oestrus have had varying rates of success,
      depending on the protocols used and the incidence of underlying problems that
      cause infertility. Embryo technologies such as multiple ovulation embryo
      transfer, in vitro embryo production, cryopreservation and cloning are being
      intensively studied but have had far lower success rates than in cattle.
      Improving the productivity of buffalo requires an understanding of their
      potential and limitations under each farming system, development of simple
      intervention strategies to ameliorate deficiencies in management, nutrition and
      healthcare, followed by judicious application of reproductive technologies that
      are sustainable with the resources available to buffalo farmers.

PMID- 18638125
TI  - Postpartum ovarian activity in South Asian zebu cattle.
AB  - Timely onset of postpartum ovarian activity is vital for optimal reproductive
      performance of dairy cows. Much depends upon genetic constitution of an animal
      although several factors interplay to govern the onset of postpartum ovarian
      activity. South Asian zebu cattle have much longer service period when compared
      with other exotic or crossbred cattle reared in the same Asian environment, which
      suggests differences in their genetic makeup. However, the cows with same genetic
      configuration expressed better reproductive potential when reared under different
      environment, such as in Brazil and Mexico, which suggests the role of extrinsic
      factors such as management, nutrition, environment and disease conditions. Better
      management of animals (provision of proper shade, water and housing, efficient
      oestrous detection and timely insemination), good quality nutrition supplemented
      with appropriate minerals and vitamins, prevention of diseases (vaccination,
      deworming, suitable therapeutic interventions) and application of biotechnology
      have helped in improving postpartum ovarian activity and, therefore, reproductive
      performance of zebu cattle in Asia. No comprehensive study appears to have been
      carried out on the various aspects of reproduction in zebu cattle reared under
      South Asian socio-agro-climatic conditions. This paper is a modest effort to
      collect what ever information available and to critically review the postpartum
      ovarian activity in zebu cattle with special reference to the effect of the
      various managemental practices and pharmacological interventions.

PMID- 18638126
TI  - Mother-offspring interactions in zebu cattle.
AB  - The knowledge of the interaction between mother and offspring might contribute to
      enhance the welfare of the offspring and to improve the reproductive efficiency
      of the cow. However, there is still little information available about such
      interaction in some cattle breeds. A series of observational studies were set up,
      addressing the mother-offspring relationships of Nelore, Guzerat and Gyr cattle
      breeds. Firstly, the behaviour of cows and calves around the time of parturition
      was described, and then, the underlying factors that affect the calves' survival
      and development were studied. Special attention was given to the failure or delay
      in the first suckling. The results together are indicative of genetic variability
      for some studied variables, indicating the possibility of selection for calf
      vigour (using latency to stand up and latency to suckle as its indicators) and
      maternal ability (using percentage of time in contact with the calves), in spite
      of the estimates of heritability were low and presented high standard deviation
      for all variables. The individual variability in their suckling behaviour and the
      efficiency in first suckling cannot be explained by a single isolated underlying
      factor. By now, there are some results available, although there are many
      questions without answers. The field is still open for the development of future
      research.

PMID- 18638127
TI  - An update on reproduction in yak and mithun.
AB  - Yak and mithun are two domesticated herbivores of high economic importance to the
      farming community living in highlands. Improved yak and mithun production could
      significantly enhance the living standards of these highlanders. Over the years,
      their dwindling numbers have been a cause of serious concern. In view of the lack
      of knowledge on the reproductive physiology of these ruminants, studies have been
      undertaken to investigate their reproductive endocrinology in recent years. This
      paper attempts to present the latest information on the endocrine changes
      associated with their various reproductive processes viz. growth and puberty,
      oestrous cyclicity and oestrous behaviour, ovulation, and, pregnancy and
      parturition. The paper also provides the recent developments on research done
      towards the enhancement of yak and mithun reproductive efficiencies through
      endocrine and embryo biotechniques.

PMID- 18638128
TI  - Follicle development in mares.
AB  - The mare provides a unique experimental model for studying follicle development
      in monovular species. Development of antral follicles in horses is characterized
      by the periodic growth of follicular waves which often involve the selection of a
      single dominant follicle. If properly stimulated, the dominant follicle will
      complete development and eventually ovulate a fertile oocyte. Regulation of
      follicular wave emergence and follicle selection involves an interplay between
      circulating gonadotropins and follicular factors that ensures that individual
      follicles are properly stimulated to grow (or to regress) at any given stage of
      follicular wave development. Periodic development of follicular waves
      continuously occurs during most of post-natal life in the mare and is influenced
      by factors such as stage of oestrous cycle, season, pregnancy, age, breed and
      individual so that different types of follicular waves (minor or major, ovulatory
      or anovulatory) and different levels of activity within waves may develop under
      different physiological conditions. Changes in gonadotropin levels and/or in the
      sensitivity of follicles to circulating gonadotropins seem to account largely for
      these physiological variations in follicle development.

PMID- 18638129
TI  - Proteins associated with the early intrauterine equine conceptus.
AB  - A critical period of early gestation in the mare involves the immobilization
      (fixation) of the encapsulated conceptus at around days 16-17. We compared the
      major proteins in the normal equine embryonic capsule and endometrial secretions
      around the period of fixation with those from pregnancies in the process of
      termination induced by administration of an analogue of prostaglandin F(2 alpha)
      (PGF(2 alpha)). Uterocalin and beta(2)-microglobulin (beta(2)M) associated with
      the embryonic capsule were proteolytically converted to smaller forms during the
      fixation period. These conversions were similar in conceptuses from control and
      treated mares. A 17 kDa cationic protein identified as a secretory phospholipase
      A2 (sPLA2) type IIA was detected bound to normal capsules but increased
      substantially in response to PGF(2 alpha). Two forms of uteroglobin were
      distinguished by partial amino acid sequences of approximately 6 kDa bands in
      flush fluids from normal pregnant uteri. After administration of PGF(2 alpha) one
      immunoreactive form of uteroglobin was preferentially increased. These studies
      demonstrate that failure of pregnancy in this model is associated with an
      increase in secretory phospholipase in the capsule and a change in the forms of
      uteroglobin in the uterine secretions.

PMID- 18638130
TI  - Heat stress, the follicle, and its enclosed oocyte: mechanisms and potential
      strategies to improve fertility in dairy cows.
AB  - Reduced reproductive performance of lactating cows during the summer is
      associated with decreased thermoregulatory competence due to intensive genetic
      selection for high milk production. This review examines the immediate and
      delayed effects of heat stress on follicular function and describes some
      potential strategies for their alleviation. It focuses on how heat stress affects
      the follicle and its enclosed oocyte, suggesting that perturbations in the
      follicular microenvironment, to which the oocytes are exposed for long periods of
      development, reduce their developmental competence. Among the potential
      alterations are reduction in gonadotropin secretion, alteration in follicular
      growth, attenuation of dominance, and disruption of steroidogenesis. Evaporative
      cooling methods are the most common strategy used to alleviate the effect of heat
      stress; however, there is a compelling need to find additional ways to improve
      fertility during the summer and autumn. Hormonal treatment to enhance removal of
      the impaired follicles by synchronization of follicular waves with GnRH and PGF2
      alpha is suggested. An alternative method is stimulation of follicular growth by
      a brief treatment with bST or FSH. Other strategies, such as timed AI and embryo
      transfer, have been recently used, making the optimization of embryo
      cryopreservation procedures highly relevant. Protection of the ovarian pool of
      oocytes from thermal stress via nutritional manipulations or administration of
      antioxidants or other survival factors should also be considered. A better
      understanding of the underlying mechanisms by which heat stress impairs fertility
      may lead to the development of additional approaches to alleviate these effects.

PMID- 18638131
TI  - Fertilization and early embryonic development in the porcine fallopian tube.
AB  - Fertilization and early embryo development relies on a complex interplay between
      the Fallopian tube and the gametes before and after fertilization. Thereby the
      oviduct, as a dynamic reproductive organ, enables reception, transport and
      maturation of male and female gametes, their fusion, and supports early embryo
      development. This paper reviews current knowledge regarding physiological
      processes behind the transport of boar spermatozoa, their storage in and release
      from the functional sperm reservoir (SR), and of the interactions that newly
      ovulated oocytes play within the tube during their transport to the site of
      fertilization. Experimental evidence of an ovarian control on sperm release from
      the SR is highlighted. Furthermore, the impact of oviductal secretion on sperm
      capacitation, oocyte maturation, fertilization and early embryo development is
      stressed.

PMID- 18638132
TI  - Mastitis in post-partum dairy cows.
AB  - Transition from the dry period to lactation is a high risk period for the modern
      dairy cow. The biggest challenge at that time is mastitis. Environmental bacteria
      are the most problematic pathogens around parturition. Coliforms are able to
      cause severe infections in multiparous cows, and heifers are likely to be
      infected with coagulase-negative staphylococci. During the periparturient period,
      hormonal and other factors make the dairy cows more or less immunocompromised. A
      successful mastitis control programme is focused on the management of dry and
      calving cows and heifers. Clean and comfortable environment, proper feeding and
      adequate supplementation of the diet with vitamins and trace elements are
      essential for maintaining good udder health. Strategies which would enhance
      closure of the teat canal in the beginning of the dry period and would protect
      teat end from bacteria until the keratin plug has formed decrease the risk for
      mastitis after calving. Dry cow therapy has been used with considerable success.
      Yet, a selective approach could be recommended rather than blanket therapy. Non
      antibiotic approaches can be useful tools to prevent new infections during the
      dry period, in herds where the risk for environmental mastitis is high.
      Vaccination has been suggested as a means to support the immune defence of the
      dairy cow around parturition. In some countries, implementation of Escherichia
      coli core antigen vaccine has reduced the incidence of severe coliform mastitis
      after calving.

PMID- 18638133
TI  - Embryonic and early foetal losses in cattle and other ruminants.
AB  - Embryo survival is a major factor affecting production and economic efficiency in
      all systems of ruminant milk and meat production. For heifers, beef and moderate
      yielding dairy cows, does and camelids it appears that fertilization generally
      lies between 90% and 100%. In high-producing dairy cows there is a less
      substantive body of literature, but it would appear that it is somewhat lower and
      perhaps more variable. In cattle, the major component of embryo loss occurs
      before day 16 following breeding with some evidence of greater losses before day
      8 in high-producing dairy cows. In cattle late embryo loss, while numerically
      much smaller than early embryo mortality loss, nevertheless, causes serious
      economic losses to producers because it is often too late to rebreed females when
      they repeat. In multiple ovulating small ruminants, the loss rate is positively
      related to ovulation rate. Systemic concentrations of progesterone, during both
      the cycle preceding and following insemination, affect embryo survival rate with
      evidence that too high or indeed too low a concentration being negatively
      associated with survival rate. Uterine expression of mRNA for progesterone
      receptor, oestradiol receptor and retinol-binding protein appears to be sensitive
      to changes in peripheral concentrations of progesterone during the first week
      after artificial insemination. Energy balance and dry matter intake during 4
      weeks after calving are critically important in determining conception rate when
      cows are inseminated at 70-100 days post-calving. Concentrate supplementation of
      cows at pasture during the breeding period has minimal effects on conception
      rates though sudden reductions in dietary intake should be avoided. For all
      systems of milk production, more balanced breeding strategies with greater
      emphasis on fertility and feed intake and/or energy balance must be developed.
      There is sufficient genetic variability within the Holstein breed for fertility
      traits. Alternative dairy breeds such as the Jersey or Norwegian Red could also
      be utilized. Genomic technology will not only provide scientists with an improved
      understanding of the underlying biological processes involved in fertilization
      and the establishment of pregnancy, but also, in the future, identify genes
      responsible for improved embryo survival. Its incorporation into breeding
      objectives would increase the rate of genetic progress for embryo survival.

PMID- 18638134
TI  - Role of cell death ligand and receptor system on regulation of follicular atresia
      in pig ovaries.
AB  - Several hundred thousand primordial follicles are present in the mammalian ovary,
      however, only a limited number develop to the pre-ovulatory stage, and then
      finally ovulate. The others, more than 99%, will be eliminated through a
      degenerative process called 'atresia'. The endocrinological regulatory mechanisms
      involved in follicular development and atresia have been characterized to a large
      extent, but the precise temporal and molecular mechanisms involved in the
      regulation of these events have remained unknown. From many recent studies, it is
      suggested that the apoptosis in ovarian granulosa cells plays a crucial role in
      follicular atresia. Notably, death ligand-receptor interaction and subsequent
      intracellular signalling have been demonstrated to be the key mechanisms
      regulating granulosa cell apoptosis. In this review, we provide an overview of
      granulosa cell apoptosis regulated by death ligand-receptor signalling. The roles
      of death ligands and receptors [Fas ligand (FasL)-Fas, tumour necrosis factor
      (TNF)alpha-TNF receptor (TNFR), and TNFalpha-related apoptosis-inducing ligand
      (TRAIL)-TRAIL receptor (TRAILR)] and intracellular death-signal mediators [Fas
      associated death domain protein (FADD), TNF receptor 1-associated death domain
      protein (TRADD), caspases, apoptotic protease-activating factor 1 (Apaf1), TNFR
      associated factor 2 (TRAF2), and cellular FLICE-like inhibitory protein (cFLIP),
      etc.] in granulosa cells will be discussed.

PMID- 18638135
TI  - Epigenetic programming of porcine endometrial function and the lactocrine
      hypothesis.
AB  - Epigenetic programs controlling development of the female reproductive tract
      (FRT) are influenced by the effects of naturally occurring bioactive agents on
      patterns of gene expression in FRT tissues during organizationally critical
      periods of foetal and perinatal life. Aberrations in such important cellular and
      molecular events, as may occur with exposure to natural or manmade steroid or
      peptide receptor-modulating agents, disrupt the developmental program and can
      change the developmental trajectory of FRT tissues, including the endometrium,
      with lasting consequences. In the pig, as in other mammals, maternal programming
      of FRT development begins pre-natally and is completed post-natally, when
      maternal effects on development can be communicated via signals transmitted in
      milk. Studies involving relaxin (RLX), a prototypic milk-borne morphoregulatory
      factor (MbF), serve as the basis for ongoing efforts to identify maternal
      programming events that affect uterine and cervical tissues in the neonatal pig.
      Data support the lactocrine hypothesis for delivery of MbFs to neonates as a
      specific consequence of nursing. Components of a maternally driven lactocrine
      mechanism for RLX-mediated signalling in neonatal FRT tissues, including evidence
      that milk-borne RLX is delivered into the neonatal circulation where it can act
      on RLX receptor (RXFP1)-positive neonatal tissues to affect their development,
      are in place in the pig. The fact that all newborn mammals drink milk extends the
      timeframe of maternal influence on neonatal development across many species.
      Thus, lactocrine transmission of milk-borne developmental signals is an element
      of the maternal epigenetic programming equation that deserves further study.

PMID- 18638136
TI  - Endocrine regulation of the establishment of spermatogenesis in pigs.
AB  - Somatic and germ cell maturation precedes the start of spermatogenesis and is
      coordinated, so efficient spermatogenesis will occur in the adults. The present
      study was conducted to evaluate endocrine regulation of germ and somatic cell
      homeostasis in the neonatal boar testis associated with the establishment of
      spermatogenesis. Testis tissue obtained from 3-, 5-, 7- and 14-day-old piglets
      were ectopically xenografted onto castrated, immunodeficient nude mice. Grafts
      were removed 22 weeks later and evaluated for growth and the establishment of
      spermatogenesis. Recipient mouse testosterone biosynthesis and follicle
      stimulating hormone (FSH) concentrations were also assayed. Testis tissue graft
      growth was significantly greater in testis grafts from 3-day donor tissue when
      compared to all other ages; 5-, 7- and 14-day-old donor tissue weights were not
      significantly different at removal. Follicle-stimulating hormone concentrations
      in recipient mice supporting testis grafts from 5-, 7- and 14-day-old donor
      tissues did not differ and were similar to normal physiological levels in age
      matched, intact nude mice. Serum FSH levels were significantly lower in recipient
      mice supporting testis grafts from 3-day-old donor tissue. Radioimmunoassay and
      biological assay indicated no differences in testosterone production by testis
      tissue grafts of varying donor age. Porcine testis tissue obtained from 3-, 5-, 7
      and 14-day-old neonatal boars were all capable of producing round and elongate
      spermatids after 22 weeks of grafting, but testis grafts from 14-day-old donors
      had a significantly greater (eightfold) percentage of seminiferous tubules with
      spermatids compared to all other donor ages (p < 0.05). Cryopreservation did not
      affect the ability of testis tissue grafts to grow, produce testosterone or
      establish spermatogenesis when compared to controls (p < 0.05). Collectively,
      these data demonstrate intrinsic differences in the biological activity of germ
      and somatic cell populations during neonatal boar testis development associated
      with the establishment of spermatogenesis.

PMID- 18638137
TI  - Male germ cell transplantation.
AB  - Transplantation of male germ line stem cells from a donor animal to the testes of
      an infertile recipient was first described in 1994. Donor germ cells colonize the
      recipient's testis and produce donor-derived sperm, such that the recipient male
      can distribute the genetic material of the germ cell donor. Germ cell
      transplantation represents a functional reconstitution assay for male germ line
      stem cells and as such has vastly increased our ability to study the biology of
      stem cells in the testis and define phenotypes of infertility. First developed in
      rodents, the technique has now been used in a number of animal species, including
      domestic mammals, chicken and fish. There are three major applications for this
      technology in animals: first, to study fundamental aspects of male germ line stem
      cell biology and male fertility; second, to preserve the reproductive potential
      of genetically valuable individuals by male germ cell transplantation within or
      between species; third, to produce transgenic sperm by genetic manipulation of
      isolated germ line stem cells and subsequent transplantation. Transgenesis
      through the male germ line has tremendous potential in species in which embryonic
      stem cells are not available and somatic cell nuclear transfer has limited
      success. Therefore, transplantation of male germ cells is a uniquely valuable
      approach for the study, preservation and manipulation of male fertility in
      animals.

PMID- 18638139
TI  - Epigenetic regulation of foetal development in nuclear transfer animal models.
AB  - Somatic cell nuclear transfer (SCNT, 'cloning') holds great potential for
      agricultural applications, generation of medical model animals, transgenic farm
      animals or by 'therapeutic cloning' for generating human embryonic stem cells for
      the treatment of human diseases. However, the low survival rate of SCNT-derived
      pregnancies represents a serious limitation of the current technology. In order
      to overcome this hurdle, a deeper understanding of the epigenetic reprogramming
      of the somatic cell nuclei and its effect on the pregnancy is needed. Here we
      review the literature on nuclear reprogramming by SCNT, including studies of gene
      expression, DNA methylation, chromatin remodelling, genomic imprinting and X
      chromosome inactivation. Reprogramming of genes expressed in the inner cell mass,
      from which the body of the foetus is formed, seems to be highly efficient.
      Defects in the extra-embryonic tissues are probably the major cause of the low
      success rate of reproductive cloning. Methods to partially overcome such problems
      exist, yet more future research is needed to find practical and efficient methods
      to remedy this problem. Improvement of the survival of foetuses is a central
      issue for the future of agricultural SCNT not only for its economic viability,
      but also because in lack of improvements in animal welfare current regulations
      can block the use of the method in the EU and several other countries.

PMID- 18638138
TI  - Sexual maturation in the bull.
AB  - In this review, we describe the process of sexual maturation in the bull calf.
      The testes of the bull grow relatively slowly until approximately 25 weeks of age
      and then a rapid phase of growth occurs until puberty, at 37-50 weeks of age.
      During the early postnatal phase of slower growth of the testis pre-spermatogonia
      and some spermatogonia are established, adult Leydig cells appear and
      undifferentiated Sertoli cells are produced. The rapid testicular growth, after
      25 weeks of age, consists of marked increases in the diameter and length of the
      seminiferous tubules, dramatic proliferation and differentiation of germ cells,
      with mature spermatozoa occurring between 32 and 40 weeks of age. The adult
      Leydig cell population is largely in place by 30 weeks of age and that of Sertoli
      cells by 30-40 weeks of age. Serum concentrations of LH increase from 4 to 5
      weeks of age, to an early postnatal peak at 12-16 weeks of age, followed by a
      decline to 25 weeks of age. Serum FSH concentrations are high postnatally,
      declining to approximately 25 weeks of age. Serum testosterone concentrations
      increase during the phase of rapid testicular growth. Hypothalamic opioidergic
      inhibition may abate transiently to allow the early postnatal increase in LH
      secretion, while testicular androgenic negative feedback probably contributes to
      the decline in gonadotropin secretion to 25 weeks of age. Several lines of study
      have led us to suggest that early postnatal gonadotropin secretion is pivotal in
      initiating the process of sexual maturation in the bull calf.

PMID- 18638141
TI  - Comparative aspects of the endotoxin- and cytokine-induced endocrine cascade
      influencing neuroendocrine control of growth and reproduction in farm animals.
AB  - Disease in animals is a well-known inhibitor of growth and reproduction. Earlier
      studies were initiated to determine the effects of endotoxin on pituitary hormone
      secretion. These studies found that in sheep, growth hormone (GH) concentration
      was elevated, whereas insulin-like growth factor-I (IGF-I) was inhibited, as was
      luteinizing hormone (LH). Examination of the site of action of endotoxin in sheep
      determined that somatotropes expressed the endotoxin receptor (CD14) and that
      both endotoxin and interleukin-I beta activated GH secretion directly from the
      pituitary. In the face of elevated GH, there is a reduction of IGF-I in all
      species examined. As GH cannot activate IGF-I release during disease, there
      appears to be a downregulation of GH signalling at the liver, perhaps related to
      altered nitration of Janus kinase (JAK). In contrast to GH downregulation, LH
      release is inhibited at the level of the hypothalamus. New insights have been
      gained in determining the mechanisms by which disease perturbs growth and
      reproduction, particularly with regard to nitration of critical control pathways,
      with this perhaps serving as a novel mechanism central to lipopolysaccharide
      suppression of all signalling pathways. This pathway-based analysis is critical
      to the developing novel strategies to reverse the detrimental effect of disease
      on animal production.

PMID- 18638140
TI  - A proposed role for VEGF isoforms in sex-specific vasculature development in the
      gonad.
AB  - Many scientists have expended efforts to determine what regulates development of
      an indifferent gonad into either a testis or ovary. Expression of Sry and
      upregulation of Sox9 are factors that initiate formation of the testis-specific
      pathway to allow for both sex-specific vasculature and seminiferous cord
      formation. Migration of mesonephric precursors of peritubular myoid cells and
      endothelial cells into the differentiating testis is a critical step in formation
      of both of these structures. Furthermore, these events appear to be initiated
      downstream from Sry expression. Sertoli cell secretion of growth factors acts to
      attract these mesonephric cells. One hypothesis is that a growth factor specific
      for these cell linages act in concert to coordinate migration of both peritubular
      and endothelial cells. A second hypothesis is that several growth factors
      stimulate migration and differentiation of mesonephric 'stem-like' cells to
      result in migration and differentiation into several different cell lineages.
      While the specific mechanism is unclear, several growth factors have been
      implicated in the initiation of mesonephric cell migration. This review will
      focus on the proposed mechanisms of a growth factor, Vascular Endothelial Growth
      Factor, and how different angiogenic and inhibitory isoforms from this single
      gene may aid in development of testis-specific vascular development.

PMID- 18638142
TI  - Energy metabolism and leptin: effects on neuroendocrine regulation of
      reproduction in the gilt and sow.
AB  - It is well established that reproductive function is metabolically gated.
      However, the mechanisms whereby energy stores and metabolic cues influence
      appetite, energy homeostasis and fertility are yet to be completely understood.
      Adipose tissue is no longer considered as only a depot to store excess energy.
      Recent findings have identified numerous genes, several neurotrophic factors,
      interleukins, insulin-like growth factor binding protein-5, ciliary neurotrophic
      factor and neuropeptide Y (NPY) as being expressed by adipose tissue during
      pubertal development. These studies demonstrated for the first time the
      expression of several major adipokines or cytokines in pig adipose tissue which
      may influence local and central metabolism and growth. Leptin appears to be the
      primary metabolic signal and is part of the adipose tissue-hypothalamic
      regulatory loop in the control of appetite, energy homeostasis and luteinizing
      hormone (LH) secretion. Leptin's actions on appetite regulation are mediated by
      inhibition of hypothalamic NPY and stimulation of proopiomelanocortin. Its
      effects on gonadotropin-releasing hormone (GnRH)/LH secretion are mediated by NPY
      and kisspeptin. Thus, leptin appears to be an important link between metabolic
      status, the neuroendocrine axis and subsequent fertility in the gilt and sow.

PMID- 18638143
TI  - Somatic cell nuclear transfer in horses.
AB  - The cloning of equids was achieved in 2003, several years after the birth of
      Dolly the sheep and also after the cloning of numerous other laboratory and farm
      animal species. The delay was because of the limited development in the horse of
      more classical-assisted reproductive techniques required for successful cloning,
      such as oocyte maturation and in vitro embryo production. When these technologies
      were developed, the application of cloning also became possible and cloned horse
      offspring were obtained. This review summarizes the main technical procedures
      that are required for cloning equids and the present status of this technique.
      The first step is competent oocyte maturation, this is followed by oocyte
      enucleation and reconstruction, using either zona-enclosed or zona-free oocytes,
      by efficient activation to allow high cleavage rates and finally by a suitable in
      vitro embryo culture technique. Cloning of the first equid, a mule, was achieved
      using an in vivo-matured oocytes and immediate transfer of the reconstructed
      embryo, i.e. at the one cell stage, to the recipient oviduct. In contrast, the
      first horse offspring was obtained using a complete in vitro procedure from
      oocyte maturation to embryo culture to the blastocyst stage, followed by non
      surgical transfer. Later studies on equine cloning report high efficiency
      relative to that for other species. Cloned equid offspring reported to date
      appear to be normal and those that have reached puberty have been confirmed to be
      fertile. In summary, horse cloning is now a reproducible technique that offers
      the opportunity to preserve valuable genetics and notably to generate copies of
      castrated champions and therefore, offspring from those champions that would be
      impossible to obtain otherwise.

PMID- 18638144
TI  - Application and commercialization of flow cytometrically sex-sorted semen.
AB  - The current technology to sort X and Y chromosome bearing sperm population
      requires individual identification and selection of spermatozoa in a modified
      high-speed flow cytometer. For farm animal species, the technology is capable of
      producing sexed sperm at greater than 90% purity. However, only in the bovine,
      the technology has reached a developmental level that allows its commercial
      application. Meanwhile, the demand for female calves has grown rapidly, which
      encourages the demand for sex-sorted semen from high genetic value bulls. The
      success of the technology will depend mainly on the fertilizing capacity of the
      sorted spermatozoa, as this is the most affecting and economically relevant
      factor. To date, fertility is still variable and is quite dependent on post-sort
      processing. New processing techniques are under investigation and will likely be
      able to improve the fertility rates after AI with sex-sorted semen. It is of
      great importance to select the right bulls and to test the sorted samples on a
      routine basis. In addition to the demand for sex-sorted semen by the cattle
      industry, there is also a significant demand expressed by pig farmers. However,
      it is still unknown if the use of sex-sorted semen through commercial pig AI will
      be economically feasible. For the pig, the combination of in vitro fertilization
      with sexed semen and non-surgical embryo transfer is an alternative that merits
      further scientific attention. Recent developments in ovine AI and ET will make it
      very likely that commercial sheep industry will adopt the sexing technology in
      their breeding concepts.

PMID- 18638145
TI  - Low-dose insemination in pigs: problems and possibilities.
AB  - Low-dose AI procedures are required by the pig industry to efficiently utilize
      emerging sperm technologies, such as cryopreservation and sex-sorting. Currently,
      several different procedures for inseminating with a low or very low number of
      spermatozoa have been described. Deep intrauterine insemination allows the
      deposition of the spermatozoa in the depth of the uterine horn, allowing a
      significant reduction in the number of spermatozoa inseminated with maintenance
      of optimal reproductive performance. Intra-oviductal laparoscopic insemination
      has been recently applied in pigs. This technique has proved to be applicable
      with diluted and sex-sorted spermatozoa. This review discusses several problems
      encountered during the development of deep intrauterine insemination and intra
      oviductal laparoscopic insemination of pigs and provides potential solutions for
      the practical application of both the technologies.

PMID- 18638146
TI  - Production of transgenic farm animals by viral vector-mediated gene transfer.
AB  - Transgenic technology holds considerable promise to advance understanding in
      biomedical and agricultural systems with some believing that one day transgenic
      animals may directly contribute to farming and breeding practice. Nevertheless,
      applications in livestock have been restricted in part by the inefficiency of the
      technology. The recent development of lentivirus vectors for transgene delivery
      may overcome some of this limitation. This presentation describes these vectors,
      their advantages and limitations.

PMID- 18638147
TI  - Use of microarray technology to profile gene expression patterns important for
      reproduction in cattle.
AB  - Fertility in cattle is a major component of many agricultural enterprises and
      there is pressure to devise methods to improve this. A number of approaches are
      ongoing, one of which is to better understand the cellular and molecular events
      of the development of reproductive tissues and to use these as targets for
      developing new strategies. Microarray technologies now allow us the potential to
      determine the transcriptional profile of expressed genes in a given tissue. This
      review focuses on the types of microarrays available for studies in cattle and
      concludes that genes associated with one or more of the cellular processes of
      cell survival/death, intracellular signalling, transcription and translation,
      cell division and proliferation and cellular metabolism are the main
      transcriptional pathways that control the development of ovarian follicles,
      oocytes, early embryos and the uterine endometrium about the time of the
      establishment of pregnancy.

PMID- 18638148
TI  - Breeding soundness evaluation and semen analysis for predicting bull fertility.
AB  - Bull fertility is influenced by numerous factors. Although 20-40% of bulls in an
      unselected population may have reduced fertility, few are completely sterile.
      Breeding soundness refers to a bull's ability to get cows pregnant. A standard
      breeding soundness evaluation identifies bulls with substantial deficits in
      fertility, but does not consistently identify sub-fertile bulls. In this regard,
      the use of frozen-thawed semen (from bulls in commercial AI centres) that meets
      minimum quality standards can result in pregnancy rates that differ by 20-25
      percentage points. Although no single diagnostic test can accurately predict
      variations in fertility among bulls that are producing apparently normal semen,
      recent studies suggested that a combination of laboratory tests were predictive
      of fertility. This review is focused on recent developments in prediction of bull
      fertility, based on assessments at the molecular, cellular and whole-animal
      levels.

PMID- 18638149
TI  - Sanitary procedures for the production of extended semen.
AB  - Semen is collected and processed from a variety of animal species for use in
      artificial insemination breeding programmes. Because of the inherent nature of
      the semen collection process, bacterial contamination of the ejaculate is a
      common occurrence. Additionally, manipulation of the ejaculate during processing
      in the laboratory can expose the sample to possible introduction of bacterial
      contamination. If preventative measures at the stud fail to adequately control
      these risks, decreases in semen quality, dose longevity and fertility may occur.
      Multiple mammalian and non-mammalian sources have been identified as origins of
      contamination in the stud. Knowledge of these sources has aided the industries in
      developing strategies that help in controlling the introduction of contaminant
      bacteria in extended semen. A primary step in minimizing contamination is in the
      practice of good hygiene by stud personnel. Prudent general sanitation protocols
      should also be followed in the laboratory, animal housing and semen collection
      areas. Cleanliness and attention to the actual semen collection process can also
      aid in reducing bacterial load originating from the stud semen donor.
      Attentiveness to all of these steps significantly contributes to an overall
      reduction in the type and amount of bacterial contamination. However, their
      complete elimination still remains unavoidable. To address residual bacteria load
      in the sample, antimicrobials are commonly used in semen extenders intended to
      promote in vitro sperm longevity beyond that of a few hours. Current research by
      the animal industries continues in the selection and prudent use of
      antimicrobials that will lead to the success and sustainability of this modality
      in controlling bacterial contamination.

PMID- 18638150
TI  - Management of goat reproduction and insemination for genetic improvement in
      France.
AB  - Reproductive seasonality observed in all breeds of goats originating from
      temperate latitudes and in some breeds from subtropical latitudes can now be
      controlled by artificial changes in photoperiod. Short days stimulate sexual
      activity, while long days inhibit it. This knowledge has allowed the development
      of photoperiodic treatments to control sexual activity in goats, for both the
      buck and doe. In the French intensive milk production system, goat AI plays an
      important role to control reproduction and, in conjunction with progeny testing,
      to improve milk production. Most dairy goats are inseminated out of the breeding
      season with deep frozen semen, after induction of oestrus and ovulation by
      hormonal treatments. This protocol provides a kidding rate of approximately 65%.
      New breeding strategies have been developed, based on the buck effect associated
      with AI, to reduce the use of hormones. With the development of insemination with
      frozen semen, a classical selection programme was set up, including planned
      mating, progeny testing and the diffusion of proved sires by inseminations in
      herds. Functional traits have become important for efficient breeding schemes in
      the dairy goat industries. Based on knowledge gained over the past decade, the
      emphasis in selective breeding has been placed on functional traits related to
      udder morphology and health. New windows have been opened based on new molecular
      tools, allowing the detection and mapping of genes of economic importance.

PMID- 18638152
TI  - Factors affecting oocyte quality: who is driving the follicle?
AB  - Mammalian ovaries contain a large stock of oocytes enclosed in primordial
      follicles. Ovarian cyclic activity induces some of these follicles to initiate
      growth towards a possible ovulation. However, most of these follicles terminate
      their growth at any moment and degenerate through atresia. In growing follicles,
      only a subset of oocytes are capable to support meiosis, fertilization and early
      embryo development to the blastocyst stage, as shown through embryo in vitro
      production experiments. This proportion of competent oocytes is increasing along
      with follicular size. Growing lines of evidence suggest that oocyte competence
      relies on the storage of gene products (messenger RNA or protein) that will be
      determinant to support early stages of embryo development, before full activation
      of embryonic genome. Given these facts, the question is: are these gene products
      stored in oocytes during late folliculogenesis, allowing an increasing proportion
      of them to become competent? Alternatively, these transcripts may be stored
      during early folliculogenesis as the oocyte grows and displays high transcription
      activity. Several arguments support this latter hypothesis and are discussed in
      this review: (i) many attempts at prolonged culture of oocytes from antral
      follicles have failed to increase developmental competence, suggesting that
      developmental competence may be acquired before antral formation; (ii) the recent
      discovery of oocyte secreted factors and of their ability to regulate many
      parameters of surrounding somatic cells, possibly influencing the fate of
      follicles between ovulation or atresia, suggests a central role of oocyte quality
      in the success of folliculogenesis. Finally, in addition to their role in
      interfollicular regulation of ovulation rate, late folliculogenesis regulation
      and atresia could also be seen as a selective process aimed at the elimination
      through follicular atresia of oocytes that did not succeed to store proper gene
      products set during their growth.

PMID- 18638151
TI  - Regulation of the spermatogonial stem cell niche.
AB  - Spermatogonial stem cells (SSCs) reside within specialized microenvironments
      called 'niches', which are essential for their maintenance and self-renewal. In
      the mammalian testis, the main components of the niche include the Sertoli cell,
      the growth factors that this nursing cell produces, the basement membrane, and
      stimuli from the vascular network between the seminiferous tubules. This review
      focuses on signalling pathways maintaining SSCs self-renewal and differentiation
      and describes potential mechanisms of regulation of the spermatogonial stem cell
      niche.

PMID- 18638153
TI  - Selected aspects of advanced porcine reproductive technology.
AB  - In vitro fertilization (IVF) of in vitro matured (IVM) oocytes in pigs has become
      the most popular method of studying gametogenesis and embryogenesis in this
      species. Furthermore, because of recent advances in in vitro culture (IVC) of IVM
      IVF embryos, in vitro production (IVP) of embryos now enables us to generate
      viable embryos as successfully as for in vivo-derived embryos and with less cost
      and in less time. These technologies contribute not only to developments in
      reproductive physiology and agriculture but also to the conservation of porcine
      genetic resources and the production of cloned or genetically modified pigs.
      However, in IVP, there still remains the problem of abnormal ploidy, which is
      caused by performing procedures under non-physiological conditions. In recent
      years, unique technologies such as intracytoplasmic sperm injection (ICSI) or
      xenografting of gonadal tissue into immunodeficient experimental animals have
      been developed to help conserve gamete resources. These technologies combined
      with IVP are expected to be useful for the conservation of gametes from important
      genetic resources. Here, we discuss the developmental ability and normality of
      porcine IVP embryos and also the utilization of ICSI and xenografting in
      advancing biotechnology in pigs.

PMID- 18638154
TI  - Climbing Mount Efficiency--small steps, not giant leaps towards higher cloning
      success in farm animals.
AB  - Despite more than a decade of research efforts, farm animal cloning by somatic
      cell nuclear transfer (SCNT) is still frustratingly inefficient. Inefficiency
      manifests itself at different levels, which are currently not well integrated. At
      the molecular level, it leads to widespread genetic, epigenetic and
      transcriptional aberrations in cloned embryos. At the organismal level, these
      genome-wide abnormalities compromise development of cloned foetuses and
      offspring. Specific molecular defects need to be causally linked to specific
      cloned phenotypes, in order to design specific treatments to correct them.
      Cloning efficiency depends on the ability of the nuclear donor cell to be fully
      reprogrammed into an embryonic state and the ability of the enucleated recipient
      cell to carry out the reprogramming reactions. It has been postulated that
      reprogrammability of the somatic donor cell epigenome is influenced by its
      differentiation status. However, direct comparisons between cells of divergent
      differentiation status within several somatic lineages have found no conclusive
      evidence for this. Choosing somatic stem cells as donors has not improved cloning
      efficiency, indicating that donor cell type may be less critical for cloning
      success. Different recipient cells, on the other hand, vary in their
      reprogramming ability. In bovine, using zygotes instead of oocytes has increased
      cloning success. Other improvements in livestock cloning efficiency include
      better coordinating donor cell type with cell cycle stage and aggregating cloned
      embryos. In the future, it will be important to demonstrate if these small
      increases at every step are cumulative, adding up to an integrated cloning
      protocol with greatly improved efficiency.

PMID- 18638155
TI  - Nuclear transfer of freeze-dried somatic cells into enucleated sheep oocytes.
AB  - Lyophilization has been used since long time to preserve yeast and bacteria
      strains. Subsequently, a great deal of efforts has been dedicated to the
      preservation in a dry state of red blood cells and platelets. However, despite
      more than 30 years passed by, no significant progress has been achieved.
      Recently, it has been reported that freeze-dried mice spermatozoa were able to
      generate normal offspring following injection into the mature mice oocytes. In
      this work, we prompted to apply the lyophilization protocol developed for mice
      spermatozoa to sheep somatic cells (lymphocytes and granulosa cells). More than
      350 enucleated sheep oocytes were injected with granulosa cells, and freeze dried
      using the protocol developed for mice sperm cells. Transplanted nuclei organized
      large pronuclei with fragmented DNA, but none of them entered the first mitosis.
      In the second part of the experiments, trehalose and EGTA were found to reduce
      significantly the extent of nuclear damage (65% and 55% intact nuclei in
      lymphocyte and granulosa cells, respectively) following freeze drying. Granulosa
      cells lyophilized with EGTA/trehalose and stored at room temperature for 3 years
      were used for nuclear transfer, and the injected oocytes were cultured in vitro
      for 7 days. Approximately 16% of the oocyte injected with freeze-dried cells
      developed into blastocysts. To conclude, we demonstrated for the first time that
      nucleated cells maintain genomic integrity after prolonged storage in a dry
      state, and we were able to achieve early embryonic development following
      injection of these cells into enucleated sheep oocytes.

PMID- 18638156
TI  - Improving medication adherence.

PMID- 18638159
TI  - Impact of an online course on infection control and prevention competencies.
AB  - AIM: This paper is a report of a study to examine the impact of an online course
      on nurses' and allied healthcare professionals' competency in infection
      prevention and control and the influence of organizational climate on knowledge
      transfer. BACKGROUND: Nosocomial infection, globalization, international travel
      and bacterial resistance are among the factors contributing to heightened
      awareness of the importance of infection prevention and control in today's
      healthcare environment. An online course in infection control was developed to
      facilitate the delivery of standardized training to large numbers of health
      providers. METHOD: A quasi-experimental, pre-and post-test study using
      questionnaires and open-ended questions was conducted in 2006 with a convenience
      sample of 76 healthcare professionals, the majority of whom were Registered
      Nurses. FINDINGS: Participants made statistically significant increases in their
      perceptions of competency in infection control following the course. The majority
      were very satisfied with the course and reported that what they had learned was
      useful and relevant to their practice. Participants who worked in supportive
      organizations that were open to change reported a higher incidence of knowledge
      transfer activities. Two course design features in particular, video and
      interactive quizzes and games, motivated learners and enhanced the learning
      experience. CONCLUSION: Online learning can provide ongoing, convenient and
      effective access to up-to-date information on best practices in infection control
      and prevention. This standardized delivery approach minimizes demand on limited
      training resources which are under strain and gives learners the opportunity to
      refresh 'rusty' infection control and prevention skills.

PMID- 18638160
TI  - A holistic programme for mothers with postnatal depression: pilot study.
AB  - AIM: This paper is a report of a pilot study to identify women's perceptions of
      participation in a holistic intervention for postnatal depression. BACKGROUND:
      Approximately 10-15% of women suffer from postnatal depression following
      childbirth. Most programmes for women with postnatal depression include
      pharmaceutical interventions; however, evaluation of women's perceptions of
      participation in holistic programmes for those suffering from postnatal
      depression show that non-pharmaceutical programmes can also be effective. METHOD:
      In-depth interviews were conducted in 2004 with a self-selected sample of 10
      women prior to and after an intervention to treat postnatal depression. FINDINGS:
      The intervention seemed capable of encouraging and facilitating a positive mother
      infant relationship while also effectively reducing the mother's anxiety levels.
      Participants commented on the supportive environment of other mothers and said
      that they found playing with their babies difficult and needed guidance and
      facilitation to do this. CONCLUSION: The pilot programme was well accepted and
      could easily be used by midwives, maternal and child health nurses and other
      appropriately trained allied health professionals.

PMID- 18638161
TI  - Roles and well-being among healthy women and women with rheumatoid arthritis.
AB  - AIM: This paper is a report of a study examining the relationships among number
      of roles, role quality, role stress, role balance, and psychological well-being
      in women diagnosed with rheumatoid arthritis. BACKGROUND: A substantial
      literature exists examining multiple roles in healthy women. However, less is
      known about multiple roles and well-being in women with a chronic illness such as
      rheumatoid arthritis. METHODS: A questionnaire study was conducted in 2003
      examining four role-related constructs (number of roles, quality of roles, role
      stress, and role balance) and psychological well-being in healthy women (n = 47)
      and women diagnosed with rheumatoid arthritis (n = 50). Correlation coefficients
      and multiple regression analyses were calculated to determine the nature of the
      relationships among the variables. FINDINGS: The two groups were similar in
      demographics except for employment, with fewer women with rheumatoid arthritis
      employed. The two groups differed statistically significantly on psychological
      well-being. Women with rheumatoid arthritis had a lower mean psychological well
      being score than healthy women. Regression analyses revealed that role stress was
      the only unique predictor of psychological well-being in healthy women, while
      role balance was the sole unique predictor among women with rheumatoid arthritis.
      CONCLUSION: Women with rheumatoid arthritis experienced lower levels of well
      being than their healthy counterparts. Examination of the relationships among the
      variables can facilitate the development of interventions to improve these
      women's mental health. Nurses are in a position to assess the psychosocial needs
      of women with rheumatoid arthritis and assist those experiencing role stress and
      role imbalance.

PMID- 18638162
TI  - Chronic fatigue: an evolutionary concept analysis.
AB  - AIM: This paper is a report of a concept analysis of chronic fatigue. BACKGROUND:
      Fatigue is a prevalent symptom encompassing both acute and chronic
      manifestations. It is chronic fatigue that is most problematic because of its
      duration and impact on life quality. The rise in prevalence of chronic conditions
      will result in a need to address coexistent symptoms, clarification of which is
      needed. Chronic fatigue is one of the most common symptoms in chronic illness.
      Clarification of the concept and an understanding of its use by discipline are
      needed. DATA SOURCES: The evolutionary method of concept analysis was used to
      ascertain the attributes, antecedents, consequences and surrogate terms for
      chronic fatigue. A review of the literature published between 1966 and 2007 was
      carried out to determine the contextual use of the concept of chronic fatigue
      among disciplines. Sources used for this analysis included CINAHL, Medline,
      PsychINFO and Social Work Abstracts and the search yielded 66 papers. RESULTS:
      The chronic fatigue experience is associated with a multitude of physical,
      psychological and social factors. The defining attributes of chronic fatigue are
      constancy, abnormality, whole-body experience, inexplicability and disabling. The
      antecedents of chronic fatigue are physical disease, psychopathology, female
      gender and a history of abuse. Consequences found include social isolation and
      stigmatization, physical inactivity, psychological disturbances and a reduced
      quality of life. CONCLUSION: Further research is needed to identify the aetiology
      of chronic fatigue and to address the social context of living with this
      disabling symptom.

PMID- 18638163
TI  - In response to: Pesut B. & Johnson J. (2008) Reinstating the 'Queen':
      understanding philosophical inquiry in nursing. Journal of Advanced Nursing
      61(1), 115-121.

PMID- 18638165
TI  - Production of a maternal-zygotic medaka mutant using hybrid sterility.
AB  - Taking advantage of the characteristics that make hybrids between Japanese and
      Chinese medaka grow well, albeit sterile, we have developed a method of germ-line
      replacement in which these hybrids are used as hosts for the production of a
      maternal-zygotic mutant. The protocol is described herein.

PMID- 18638166
TI  - Novel method for the nuclear transfer of adult somatic cells in medaka fish
      (Oryzias latipes): use of diploidized eggs as recipients.
AB  - Until recently, the nuclear transfer of adult somatic cell nuclei in fish has
      been unsuccessful. This is primarily because of chromosomal aberrations in
      nuclear transplants, which are thought to arise due to asynchrony between the
      cell cycles of the recipient egg and donor nucleus. We recently succeeded in
      circumventing this difficulty by using a new nuclear transfer method in medaka
      fish (Oryzias latipes). Instead of enucleated eggs, the method uses non
      enucleated and diploidized eggs, obtained by retention of the second polar body
      release, as recipients in the nuclear transfer of primary culture cells from the
      caudal fin of an adult green fluorescent protein gene (GFP)-transgenic strain. We
      found that 2.7% of the reconstructed embryos grew into diploid and fertile adults
      exhibiting donor expression characteristics and transmission of the GFP marker
      gene to progeny. The mechanism underlying the generation of nuclear transplants
      using this method is unknown at present; however, analyses of donor and recipient
      nuclei behavior and the cytoskeletal mechanisms involved in the early
      developmental stages, as well as the special ability of diploidized eggs to
      facilitate reprogramming of the donor nuclei will result in elucidation of the
      mechanism.

PMID- 18638167
TI  - Gallera method of chick embryo culture in vitro supports better growth compared
      with original New method.
AB  - An avian embryo is a valuable model system for vertebrate embryology. Easy
      availability, accessibility to various developmental stages and amenability of
      organ fields makes the chick embryo one of the favored model systems. Seminal
      discoveries regarding organogenesis and vertebrate morphogenesis have been made
      using chick embryos cultured in vitro. Dennis A.T. New revolutionized chick
      embryo culture methodology with his development of a single glass ring
      explantation technique. Many modifications and/or embellishments were introduced
      after the New era of embryo culture. A double glass ring method for chick embryo
      culture introduced by Gallera and Nicolet is compared with the original New
      method and the EASY method in this study. In addition, a video of culture methods
      is presented as a valuable tool in learning about and/or teaching techniques of
      chick embryo culture.

PMID- 18638169
TI  - Intravenous catheter infections in pulmonary arterial hypertension.

PMID- 18638168
TI  - Congenic method in the chick limb buds by electroporation.
AB  - Electroporation is a powerful tool with which to study limb development. Limb
      development, however, remains an intricate series of events, requiring the
      precise dissection of developmental processes using relevant transgenes. In this
      review, we describe the anatomy of the limb field as the basis of targeted
      electroporation, and specific expression vectors are discussed. We share a useful
      protocol for electroporation of chick limb buds, and the expression pattern of
      enhanced green fluorescent protein in the limb buds is used to demonstrate
      relevant embryonic patterning. Finally, useful trouble-shooting techniques are
      described.

PMID- 18638170
TI  - Guidelines for the prevention of central venous catheter-related blood stream
      infections with prostanoid therapy for pulmonary arterial hypertension.
AB  - Intravenous prostanoids are the backbone of therapy for advanced pulmonary
      arterial hypertension (PAH) and have improved long-term outcome and quality of
      life. Currently, two prostanoids are approved by the US Food and Drug
      administration for parenteral administration: epoprostenol (Flolan) and
      treprostinil (Remodulin). Chronic intravenous therapy presents considerable
      challenges for patients and caregivers who must learn sterile preparation of the
      medication, operation of the pump, and care of the central venous catheter.
      Patients are routinely counseled and advised regarding the risks of CR-BSIs and
      catheter care before central line insertion. Central line infections as well as
      bacteremia are well documented risks of chronic intravenous therapy and may
      significantly contribute to morbidity and mortality. Recent reports have
      suggested a possible increase in CR-BSI; therefore, the Scientific Leadership
      Council of the Pulmonary Hypertension Association decided to provide guidelines
      for good clinical practice regarding catheter care. Although data exits regarding
      patients with central venous catheters and the risk of blood stream infections in
      patients with cancer or other disorders, there is little data regarding the
      special needs of patients with pulmonary arterial hypertension requiring central
      venous access. These guidelines are extrapolated from the diverse body of
      literature regarding central venous catheter care.

PMID- 18638171
TI  - Right heart function and haemodynamics in pulmonary hypertension.
AB  - The primary challenge in the care of the patient with advanced pulmonary arterial
      hypertension (PAH) is right ventricular dysfunction with concomitant right heart
      failure. Right heart function is closely tied to survival in this disease, and
      there is a growing interest in the study of this unique structure. While
      echocardiography and cardiac magnetic resonance (CMR) have augmented our ability
      to image the right ventricle (RV), the primary means of assessing right heart
      function remains right heart catheterisation. Several of the currently available
      treatments for PAH have been shown to have effects on the RV, not just the
      pulmonary vasculature, and, in future, therapies aimed at optimizing right
      ventricular function may allow better outcomes in this challenging disease. New
      directions in right ventricular assessment including measurement of pulmonary
      vascular impedance and more widespread availability of CMR may allow greater
      knowledge about this little studied, yet highly important, right side of the
      heart.

PMID- 18638172
TI  - Pulmonary hypertension and left heart disease: emerging concepts and treatment
      strategies.
AB  - At least two thirds of patients with chronic severe left heart disease have
      associated pulmonary hypertension, and mortality associated with biventricular
      failure is >two-fold higher compared with isolated left ventricular failure. This
      review considers and discusses emerging concepts and strategies from recent
      studies of specific treatments in populations with pulmonary hypertension
      complicating overt left ventricular dysfunction. While the results reported in
      the studies considered are encouraging, to date there are no large randomised
      studies of specific treatments in populations with pulmonary hypertension
      complicating overt left ventricular dysfunction.

PMID- 18638173
TI  - Reflections on independence in nurse practitioner practice.
AB  - PURPOSE: To examine factors that influence the ability of nurse practitioners
      (NPs) to practice as independent primary care providers. DATA SOURCES: Extensive
      literature search on CINAHL, OVID, MEDLINE, Internet journal sources, and
      professional association Web sites. CONCLUSIONS: The legal authority for NPs to
      practice independently is recognized; however, the ability to put that authority
      into practice is undermined by the historical failure of political, professional,
      and social entities to recognize NPs as providers capable of providing primary
      care autonomously. Nonrecognition is responsible for complex reimbursement
      policies (both federal and state) that economically and professionally restrain
      the NP role; hence, NPs remain in a financially dependent relationship despite 40
      years of proven safe practice. NPs must articulate their independence as
      practitioners more vociferously in order to meet society's healthcare
      requirements, as well as to attain professional fulfillment and forge collegial
      relationships. IMPLICATIONS FOR PRACTICE: NPs will never be seen as members of a
      profession by either themselves or others without the practicality of
      independence and autonomy. Although legal independence is a fact, real practice
      independence in the pragmatic sense is contingent upon reimbursement. Without
      fiscal sustainability, practice independence is an impossibility. And, without
      professional autonomy, NPs will have only an employee's voice in the dynamic
      healthcare system in which they are really key players in providing healthcare
      services to the poor and undeserved populations.

PMID- 18638174
TI  - Can't stop dancing: could it be St. Vitus' dance?
AB  - PURPOSE: To inform providers of one of the rare but significant consequences that
      result from not diagnosing and treating streptococcal pharyngitis: Sydenham's
      chorea (St. Vitus' dance). DATA SOURCES: Current Internet sources including
      review articles, informational articles, online medical textbooks, and
      professional organization Web sites. CONCLUSION: It is vital that each case of
      streptococcal pharyngitis be treated with appropriate antibiotic therapy. Doing
      so will help prevent the sequelae associated with streptococcal infections, such
      as acute rheumatic fever (ARF) and Sydenham's chorea. IMPLICATIONS FOR PRACTICE:
      Streptococcal pharyngitis is a common illness that has the potential to cause
      very serious consequences. The consequences may be life altering, such as
      suffering permanent heart damage. With appropriate diagnosis and treatment with
      antibiotics, the sequelae of ARF and Sydenham's chorea can be prevented.

PMID- 18638175
TI  - Depression and anxiety outcomes at a free clinic in a rural state.
AB  - PURPOSE: To describe the diagnostic and treatment patterns for depression and
      anxiety in clients receiving care at a free clinic. DATA SOURCES: Charts for 43
      clients who received antidepressant or anxiolytic medications were randomly
      selected and reviewed. CONCLUSIONS: Clients presented to the clinic symptomatic;
      almost two thirds had been treated elsewhere. Most clients received
      pharmacological treatment and referral for counseling. Forty-four percent of the
      clients were still being treated at their last visit, but 33% were no longer
      being seen, and it could not be determined if they were receiving care at another
      clinic. IMPLICATIONS FOR PRACTICE: If sustained relationships with clients with
      depression and anxiety can be developed, appropriate care can be provided.

PMID- 18638176
TI  - Nurse practitioners' knowledge and practice regarding malignant melanoma
      assessment and counseling.
AB  - PURPOSE: To evaluate the knowledge base and clinical practices of nurse
      practitioners (NPs) within the states of Illinois and California regarding
      malignant melanoma. DATA SOURCES: Data sources included responses to a 57-item
      self-administered questionnaire and 15-item demographic survey. A convenience
      sample of 93 certified NPs from Illinois and California, aged 27-68 years,
      participated in the study. Participants responded to questions relating to
      knowledge of malignant melanoma preventive measures, risk factors, barriers to
      performing malignant melanoma assessments, and lesion recognition. CONCLUSIONS:
      Overall, the NPs in this study demonstrated adequate knowledge about malignant
      melanoma but conducted general skin and malignant melanoma assessments less than
      half of the time and provided patient teaching about preventive measures and risk
      factors only occasionally. While California NPs demonstrated significantly
      greater knowledge about malignant melanoma than the Illinois NPs, they performed
      less skin and malignant melanoma assessments and provided less teaching. The most
      frequently cited barrier to performing malignant melanoma examinations for both
      states was time constraints. IMPLICATIONS FOR PRACTICE: NPs can play a pivotal
      role in reducing the morbidity and mortality of malignant melanoma through
      competent skin assessments and patient education and encouraging patients to
      pursue healthy lifestyles. Improving NPs' assessment skills and knowledge about
      malignant melanoma, however, is critical to achieving this goal.

PMID- 18638177
TI  - An innovative approach to peer review for the advanced practice nurse--a focus on
      critical incidents.
AB  - PURPOSE: To provide an overview of the development and implementation of a peer
      review process for advanced practice nurses (APNs) based on critical incidents
      that provide meaningful evaluation of practice and meets the needs of APNs across
      multiple care specialties and practice situations. DATA SOURCES: A review of the
      literature and evaluation of the existing peer review process currently in place
      at a large tertiary care facility. CONCLUSIONS: Peer review is central to self
      regulation and professional practice for APNs. It has been proposed that APNs of
      similar rank and clinical expertise should participate in peer review. APN peer
      review and evaluation have traditionally existed as a component of performance
      evaluation, evaluation of practice patterns, and compliance monitoring, and to
      evaluate quality indicators. We found no examples of peer review in the context
      of evaluating a critical incident in the literature. The APN Peer Review
      Committee and the review process were developed at our institution to provide
      peer input and communication to all credentialed APNs in incidents regarding
      appropriateness of care and scope of practice. IMPLICATIONS FOR PRACTICE: APNs
      must assure that they have a voice in the peer review process. Representation by
      peers of similar specialty and rank is an important component in the peer
      evaluation process. The establishment of the APN Peer Review Committee served
      this purpose for our institution.

PMID- 18638178
TI  - Nurse practitioners' communication styles and their impact on patient outcomes:
      an integrated literature review.
AB  - PURPOSE: The purpose of this review was to examine the published research from
      1999 to 2005 describing nurse practitioner (NP)-patient interactions and to
      determine the best practice to enhance patient outcomes. DATA SOURCES: Databases
      searched included Academic Search Elite, Cumulative Index to Nursing and Allied
      Health Literature (CINAHL), Health Source Consumer Edition, Health Source
      Nursing/Academic Edition, Medline, and PsychInfo. CONCLUSIONS: Two communication
      styles described in the literature and determined by authors were (a) biomedical
      and (b) biopsychosocial. The biopsychosocial style is identified as patient
      centered communication. Seven studies were then analyzed for NPs' communication
      styles and the impact that they had on patient outcomes. The studies analyzed
      demonstrated that biopsychosocial (patient-centered) communication style
      positively influences patient outcomes as evidenced by (a) improved patient
      satisfaction, (b) increased adherence to treatment plans, and (c) improved
      patient health. IMPLICATIONS FOR PRACTICE: The results of this review indicate
      that patient-centered communication incorporated into the NPs' practice is
      associated with improving patient outcomes such as (a) improved patient
      satisfaction, (b) increased adherence to treatment plans, and (c) improved
      patient health. Future research needs to be performed in order to fully study the
      relationship between NPs using patient-centered communication style and its
      impact on patient outcomes. Clinical recommendations are made based on findings
      of the integrated literature review.

PMID- 18638179
TI  - Perspectives on the impact of early parent loss in adulthood in the UK:
      narratives provide the way forward.

PMID- 18638181
TI  - Hepatitis E virus infection among domestic animals in eastern China.
AB  - Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animal
      were reported as reservoirs. Antibodies to HEV and HEV RNA have been detected in
      some Chinese population and swine groups but few other domestic animals. In this
      study, to investigate the HEV prevalence, we tested sera from 788 pigs, 100 cows,
      50 goats, 49 horses, 101 pet dogs, 105 chickens, 47 duck and 45 pigeons in
      eastern China for anti-HEV immunoglobulin G (IgG). We also tested 50% of the
      swine sera, all of sera from the other domestic animals and 13 Shanghai human
      sera which were positive for anti-HEV immunoglobulin M (IgM) for HEV RNA using
      reverse transcriptase-polymerase chain reaction. Our results indicated that 82.5%
      (222/269) of the sows, 53.9% (104/193) of the 4- to 6-month-old swine, 63.4%
      (168/265) of the 1- to 3-month-old swine, 55.7% (34/61) of the slaughterhouse
      swine, 24% (12/50) of the goats, 16.3% (8/49) of the horses, 17.8% (21/101) of
      the pet dogs, 6% (6/100) of the cows, 12.8% (6/47) of the ducks, 4.4% (2/45) of
      the pigeons and 1.9% (2/105) of the chickens exhibited positive for anti-HEV IgG.
      Inhibition assay confirmed the infection with HEV or HEV-like viruses in these
      domestic animals except pigeons and chickens. From the sera, we isolated 18 swine
      HEV strains, one horse HEV strain and two human HEV strains. Sequence analysis
      showed that the horse HEV isolate and one swine isolate belonged to genotype 3.
      The other isolates belonged to genotype 4. The two human isolates were
      phylogenetically closely related to eight of the swine isolates. In short, the
      presence of anti-HEV antibody had been confirmed in several species of domestic
      animals in eastern China and HEV RNA has been identified in swine, human and
      horse. This suggested that the authorities should pay more attention to the
      prevalence of HEV in eastern China.

PMID- 18638182
TI  - Seroprevalence of Toxoplasma gondii antibodies in free-ranging mithuns (Bos
      frontalis) from India.
AB  - Studies conducted on free-ranging mithuns of Nagaland, India revealed that the
      overall seroprevalence of antibodies to Toxoplasma gondii in mithun was 42% (95%
      CI = 33-51) when detected by modified direct agglutination test. Highest
      (prevalence = 57%, 95% CI = 43-71) seroprevalence was found in mithuns above 3
      years of age and the lowest (prevalence = 18%, 95% CI =4-32) in mithuns of 1-2
      years old. No statistically significant difference was observed between male
      (prevalence = 40%, 95% CI = 26-54) and female (prevalence = 44%, 95% CI = 31-57)
      seroprevalences. The study also revealed that the maximum number (57%) of animals
      with the highest titre (1 : 3200) were above 3 years of age. This is the first
      serological survey for Toxoplasma gondii antibodies in free-ranging mithuns from
      India.

PMID- 18638183
TI  - Autochthonous Dirofilaria (Nochtiella) repens infection in dogs in Kuwait.
AB  - Human dirofilariasis caused by Dirofilaria repens is a rare but increasingly
      reported zoonosis in the Middle East. However, eligible animal reservoirs seldom
      have been investigated in the area until now. Seven (1.8 percent) out of 381 dogs
      examined in Kuwait carried D. repens microfilariae showing compatible cutaneous
      clinical signs and positive response to the adulticide and microfilaricide
      therapies. This study indicates that dogs from Kuwait are natural hosts of D.
      repens and therefore act as an animal reservoir for the zoonotic condition.

PMID- 18638184
TI  - Spatially resolved cathodoluminescence of luminescent materials using an EDX
      detector.
AB  - Panchromatic cathodoluminescence (CL) maps were collected in a scanning electron
      microscope equipped with an EDX (energy dispersive x-ray analysis) detector.
      These CL maps can readily be correlated with elemental maps obtained by EDX.
      Although EDX detectors are designed to be insensitive to light and therefore not
      optimized for high sensitivity CL measurements, high-resolution images can be
      obtained from luminescent materials without the need for additional hard- or
      software. The method was tested on highly luminescent BaAl(2)S(4):Eu(2+) thin
      films that have a potential use in flat panel displays. The spectral response and
      linearity of the overall system was determined by means of monochromatic light
      sources, illuminating the sample through an optical fibre. We studied the
      response of the EDX detector to the intensity of the incoming light as well as
      the influence of the detector settings. The observations were explained by
      numerical simulations.

PMID- 18638185
TI  - Quantitative determination of the reduction of phototoxicity and photobleaching
      by controlled light exposure microscopy.
AB  - Phototoxicity and photobleaching are major limitations in live-cell fluorescence
      microscopy. They are caused by fluorophores in an excited singlet or triplet
      state that generate singlet oxygen and other reactive oxygen species. The
      principle of controlled light exposure microscopy (CLEM) is based on non-uniform
      illumination of the field of view to reduce the number of excited fluorophore
      molecules. This approach reduces phototoxicity and photobleaching 2- to 10-fold
      without deteriorating image quality. Reduction of phototoxicity and
      photobleaching depends on the fluorophore distribution in the studied object, the
      optical properties of the microscope and settings of CLEM electronics. Here, we
      introduce the CLEM factor as a quantitative measure of reduction in phototoxicity
      and photobleaching. Finally, we give a guideline to optimize the effect of CLEM
      without compromising image quality.

PMID- 18638186
TI  - Preservation of ultrastructure and immunoreactivity in cryosections of brain
      tissue stored in a sucrose-gelatin solution at freezing temperatures.
AB  - We evaluated the preservation of ultra-structure and immunoreactivity in
      cryosections of central nervous system tissue mounted with and stored in a
      sucrose-gelatin solution for one month at -20 degrees C or -80 degrees C. The
      ultra-structure of synaptic structure in these sections was well preserved and
      comparable to that of freshly cut cryosections. Quantitative analysis of
      mitochondrial ultra-structure demonstrated gradually lower degrees of
      preservation in sections stored at -20 degrees C and -80 degrees C compared with
      that in freshly cut sections. We observed distinct metabotropic glutamate
      receptor 1 (mGluR1)-immunogold labelling at peri-synaptic sites in freshly cut
      sections and also in those stored at -20 degrees C and -80 degrees C.
      Quantitative analysis of mGluR1 immunoreactivity revealed that the total number
      of immunogold particles per synapse and the number of non-specifically bound
      particles were similar under all three conditions. However, the percentage of
      gold particles bound to a specific synaptic region was greatest in freshly cut
      sections (79.0%) and progressively lower in sections stored at -20 degrees C
      (76.1%), in which sections were not frozen, and in sections stored at -80 degrees
      C (68.0%). These data indicate that ultra-thin cryosections may be conveniently
      stored in a sucrose-gelatin solution at -20 degrees C for cryoultramicrotomy
      immunolabelling.

PMID- 18638187
TI  - Focal adhesion interactions with topographical structures: a novel method for
      immuno-SEM labelling of focal adhesions in S-phase cells.
AB  - Current understanding of the mechanisms involved in osseointegration following
      implantation of a biomaterial has led to adhesion quantification being
      implemented as an assay of cytocompatibility. Such measurement can be hindered by
      intra-sample variation owing to morphological changes associated with the cell
      cycle. Here we report on a new scanning electron microscopical method for the
      simultaneous immunogold labelling of cellular focal adhesions and S-phase nuclei
      identified by BrdU incorporation. Prior to labelling, cellular membranes are
      removed by tritonization and antigens of non-interest blocked by serum
      incubation. Adhesion plaque-associated vinculin and S-phase nuclei were both
      separately labelled with a 1.4 nm gold colloid and visualized by subsequent
      colloid enhancement via silver deposition. This study is specifically concerned
      with the effects microgroove topographies have on adhesion formation in S-phase
      osteoblasts. By combining backscattered electron (BSE) imaging with secondary
      electron (SE) imaging it was possible to visualize S-phase nuclei and the
      immunogold-labelled adhesion sites in one energy 'plane' and the underlying
      nanotopography in another. Osteoblast adhesion to these nanotopographies was
      ascertained by quantification of adhesion complex formation.

PMID- 18638188
TI  - Application of elemental microanalysis to elucidate the role of spherites in the
      digestive gland of the helicid snail Chilostoma lefeburiana.
AB  - In this case study we present an application of different analytical electron
      microscopic methods in biology, to elucidate their usefulness in such
      investigations. Using analytical electron microscopy, spherites in the digestive
      gland cells of the helicid snail Chilostoma lefeburiana were examined at three
      stages: just before the non-feeding period of over-wintering in November, in the
      middle of over-wintering in February and at its end in March. A detailed
      characterization of changes in the elemental composition of the spherites was
      characterized by a combination of transmission electron microscopy (TEM), energy
      dispersive x-ray spectroscopy (EDXS), electron energy-loss spectroscopy (EELS)
      and energy filtering TEM (EFTEM). During over-wintering, the spherites passed the
      following changes. Before over-wintering in November, they consisted of striking
      concentric layers of electron-dense and electron-lucent zones, while in February
      and March they showed clear empty zones between materials of different electron
      density. In November spherites, C, O, Ca, P, Cl, Fe, Si, Na, K, Mg and S were
      detected, whereas in February ones C, O, N, Cl, Si and S were found and only C,
      O, N, Si and Cl were detected in March spherites. It is suggested that the
      elements missing in February and March were used in different physiological
      processes during over-wintering, like (1) the maintenance of the appropriate
      elemental composition of the internal environment, (2) accumulation of non-toxic
      waste materials that cannot be metabolized and (3) avoiding potential
      intoxication by contamination with toxic metals.

PMID- 18638189
TI  - Segmentation of touching cell nuclei using gradient flow tracking.
AB  - Reliable cell nuclei segmentation is an important yet unresolved problem in
      biological imaging studies. This paper presents a novel computerized method for
      robust cell nuclei segmentation based on gradient flow tracking. This method is
      composed of three key steps: (1) generate a diffused gradient vector flow field;
      (2) perform a gradient flow tracking procedure to attract points to the basin of
      a sink; and (3) separate the image into small regions, each containing one
      nucleus and nearby peripheral background, and perform local adaptive thresholding
      in each small region to extract the cell nucleus from the background. To show the
      generality of the proposed method, we report the validation and experimental
      results using microscopic image data sets from three research labs, with both
      over-segmentation and under-segmentation rates below 3%. In particular, this
      method is able to segment closely juxtaposed or clustered cell nuclei, with high
      sensitivity and specificity in different situations.

PMID- 18638190
TI  - Quantitative image correction and calibration for confocal fluorescence
      microscopy using thin reference layers and SIPchart-based calibration procedures.
AB  - The fluorescence intensity image of an axially integrated through-focus series of
      a thin standardized uniform fluorescent layer can be used for image intensity
      correction and calibration in sectioning microscopy. This intensity image is in
      fact available from the earlier introduced Sectioned Imaging Property (SIP)
      charts (Brakenhoff et al., 2005). It is shown that the integrated intensity of a
      z-stack from a biological sample, imaged under identical conditions as the layer,
      can be calibrated in terms of fluorescence layer units of the calibration layer.
      The imaging after such calibration becomes, as a first approximation, independent
      of the microscope system and imaging conditions. This is demonstrated on axially
      integrated images of standard fluorescent beads and standard BPAE Fluorocells.
      Corrections on the microscope imaging conditions include shading effects, imaging
      with different magnifications and objectives, and using different microscope
      systems. It is also shown that with the present approach the actual underlying
      three-dimensional (3D) fluorescence data set itself can be corrected for
      variations in point spread function (PSF) imaging efficiency over the imaging
      data cube. Realizing such calibration between imaging conditions or systems
      requires basically only the 2D fluorescer molecule density of the reference
      layers and the section distances with which the layer data are collected.

PMID- 18638191
TI  - Image segmentation of liver fibrosis.
AB  - Quantitation of connective tissue versus parenchymal tissue compartments is
      important in assessment of fibrosis (scarring) and its progression in liver
      disease. This paper presents a two-step algorithm for quantifying fibrosis in
      liver biopsies stained with Sirius red. With this staining technique, collagen
      and cell nuclei appear similarly stained, whereas cytoplasm appears pale. The
      first step of the algorithm is to separate similarly stained areas occupied by
      collagen and hepatocyte nuclei. Since the total area of the combined collagen and
      cell nuclei is usually much smaller than the remaining liver parenchyma, a non
      linear intensity mapping is applied to enhance the smaller cluster in order to
      match the larger one in both intensity and size. The second step is to
      differentiate the fibrotic areas usually having irregular shapes from hepatocyte
      nuclei that have relatively uniform size and have circular shape. The proposed
      algorithm has been applied to quantify the development of progressive fibrosis
      and its possible regression in liver biopsy specimens from patients with
      parenteral-induced liver injury undergoing intestinal transplantation.

PMID- 18638192
TI  - Application of wavelet denoising to improve compression efficiency while
      preserving integrity of digital micrographs.
AB  - Modern microscopy methods require efficient image compression techniques owing to
      collection of up to thousands of images per experiment. Current irreversible
      techniques such as JPEG and JPEG2000 are not optimized to preserve the integrity
      of the scientific data as required by 21 CFR part 11. Therefore, to construct an
      irreversible, yet integrity-preserving compression mechanism, we establish a
      model of noise as a function of signal in our imaging system. The noise is then
      removed with a wavelet shrinkage algorithm whose parameters are adapted to local
      image structure. We ascertain the integrity of the denoised images by measuring
      changes in spatial and intensity distributions of registered light in the
      biological images and estimating changes of the effective microscope MTF. We
      demonstrate that the proposed denoising procedure leads to a decrease in image
      file size when a reversible JPEG2000 coding is used and provides better fidelity
      than irreversible JPEG and JPEG2000 at the same compression ratio. We also
      demonstrate that denoising reduces image artefacts when used as a pre-filtering
      step prior to irreversible image coding.

PMID- 18638193
TI  - Fluorescence resonance energy transfer of GFP and YFP by spectral imaging and
      quantitative acceptor photobleaching.
AB  - To study protein-protein interactions by fluorescence energy transfer (FRET), the
      proteins of interest are tagged with either a donor or an acceptor fluorophore.
      For efficient FRET, fluorophores need to have a reasonable overlap of donor
      emission and acceptor excitation spectra. However, given the relatively small
      Stokes shift of conventional fluorescent proteins, donor and acceptor pairs with
      high FRET efficiencies have emission spectra that are difficult to separate. GFP
      and YFP are widely used in fluorescence microscopy studies. The spectral
      qualities of GFP and YFP make them one of the most efficient FRET donor-acceptor
      couples available. However, the emission peaks of GFP (510 nm) and YFP (527 nm)
      are spectrally too close for separation by conventional fluorescence microscopy.
      Difficulties in simultaneous detection of GFP and YFP with a fluorescence
      microscope are eliminated when spectral imaging and subsequent linear unmixing
      are applied. This allows FRET microscopy using these tags to study protein
      protein interactions. We adapted the linear unmixing procedure from commercially
      available software (Zeiss) for use with acceptor photobleaching FRET using GFP
      and YFP as FRET pair. FRET efficiencies up to 52% for a GFP-YFP fusion protein
      were measured. To investigate the applicability of the procedure, we used two
      constituents of the nucleotide excision repair system, which removes UV-induced
      single-strand DNA damage. ERCC1 and XPF form a heterodimeric 5' endonuclease in
      nucleotide excision repair. FRET between ERCC1-GFP and XPF-YFP occurs with an
      efficiency of 30%.

PMID- 18638195
TI  - Phase resolving microscopy by multi-plane diffraction detection.
AB  - An easily applicable quantitative phase-contrast microscopy is presented. A
      bright-field microscope with a coherent illumination is used. Only a series of
      diffraction images is taken in different distances from the sample. For
      reconstruction, a conjugate gradient technique as a new variant of phase
      retrieval technique is developed. The technique is experimentally investigated in
      detail. A phase accuracy up to 0.07 rad or a height accuracy of 13 nm in
      transmission for a binary test sample is reached, respectively.

PMID- 18638194
TI  - Shape normalization of 3D cell nuclei using elastic spherical mapping.
AB  - Topological analysis of cells and subcellular structures on the basis of image
      data, is one of the major trends in modern quantitative biology. However, due to
      the dynamic nature of cell biology, the optical appearance of different cells or
      even time-series of the same cell is undergoing substantial variations in shape
      and texture, which makes a comparison of shapes and distances across different
      cells a nontrivial task. In the absence of canonical invariances, a natural
      approach to the normalization of cells consists of spherical mapping, enabling
      the analysis of targeted regions in terms of canonical spherical coordinates,
      that is, radial distances and angles. In this work, we present a physically-based
      approach to spherical mapping, which has been applied for topological analysis of
      multichannel confocal laser scanning microscopy images of human fibroblast
      nuclei. Our experimental results demonstrate that spherical mapping of entire
      nuclear domains can automatically be obtained by inverting affine and elastic
      transformations, performed on a spherical finite element template mesh.

PMID- 18638196
TI  - Electron microscopy study of different stages of oxidation of Ti-47Al-2Nb-2Cr
      0.15B and Ti-45Al-15Nb at 900 degrees C.
AB  - The initial stage of oxidation of Ti-47Al-2Nb-2Cr-0.15B and Ti-45Al-15Nb alloys
      was studied. Studies reveal that the X and NbCr(2) phases will form in advance in
      the transition layer of the 2Nb2Cr alloy compared with the 15Nb alloy. The
      adherence between the nitride layer and underling layer is good. However, an
      obvious boundary exists between the mixed layer and the inner layer. The
      recrystallizing of the base alloy leads to an increase of the volume fraction of
      grain boundaries that can increase the oxidation rate at the initial oxidation
      stage. An Nb-based compound forms in the transition layer, which can prevent the
      formation of X phase.

PMID- 18638197
TI  - Knife-edge scanning microscopy for imaging and reconstruction of three
      dimensional anatomical structures of the mouse brain.
AB  - Anatomical information at the cellular level is important in many fields,
      including organ systems development, computational biology and informatics.
      Creating data sets at resolutions that provide enough detail to reconstruct
      cellular structures across tissue volumes from 1 to 100 mm(3) has proven to be
      difficult and time-consuming. In this paper, we describe a new method for
      staining and imaging large volumes of tissue at sub-micron resolutions. Serial
      sections are cut using an automated ultra-microtome, whereas concurrently each
      section is imaged through a light microscope with a high-speed line-scan camera.
      This technique, knife-edge scanning microscopy, allows us to view and record
      large volumes of tissue in a relatively small amount of time (approximately 7
      mm(2) s(-1)). The resolution and scanning speed of knife-edge scanning microscopy
      provides a new method for imaging tissue at sufficient resolution to reconstruct
      maps of cellular distribution and morphology. We show that these techniques
      preserve the alignment of serial sections accurately enough to allow for
      reconstruction of neuronal processes and microvasculature. Expanding these
      techniques to other tissues opens up the possibility of creating fully
      reconstructed cellular maps of entire organs.

PMID- 18638198
TI  - Electronic property investigations of single-walled carbon nanotube bundles in
      situ within a transmission electron microscope: an evaluation.
AB  - We have evaluated a combined transmission electron microscopy (TEM)-scanning
      tunnelling microscopy (STM) (hence TEM-STM) sample holder for the investigation
      of the mechanical and electrical properties of individual bundles of single
      walled carbon nanotubes (SWCNTs) together with their simultaneous observation,
      analysis and mechanical modification in the TEM. Current-voltage (I-V)
      measurements from bundles of SWCNTs were observed to change as the bundles were
      deformed both reversibly and irreversibly, although the observed behaviour was
      somewhat complex. Electron energy loss spectroscopy (EELS) analysis revealed
      measurable changes in the bonding of the carbon atoms within the graphene layers
      upon bundle deformation, with measurable changes in the pi*/(pi*+sigma*) peak
      ratios observed at the carbon K-edge. Reversible deformation of the bundles was
      consistent with the sensitivity of sigma bonding to deviations from nonplanarity,
      whereas irreversible deformation was consistent with the introduction of
      nonhexagonal defects into the graphene sheets.

PMID- 18638199
TI  - Measurement of the absorption of concentrated dyes and their use for quantitative
      imaging of surface topography.
AB  - We propose a method to image the surface topography of transparent objects. The
      space between the object and the opposite closely positioned surface (such as a
      cover glass or a slide) is filled with a strongly absorbing dye. The contrast is
      generated by recording a transmission image at a wavelength where the dye
      absorbs. Since the transmitted intensity depends on the depth of the dye layer,
      it carries information about the relief of the tested surface. With sufficiently
      concentrated dyes, nanometre unevenness of a surface can be detected. By using
      less-concentrated solutions, it is possible to image and measure larger objects,
      such as biological cells. At the present stage, biological applications of the
      method are only semi-quantitative, but the method still provides detailed
      information about cell shapes that is not readily obtainable with other imaging
      techniques. Conversion of the image grey scale into the units of vertical
      distance requires knowledge of the absorption coefficient of the dye. The same
      method that is used for imaging can be adapted to measure the absorption
      coefficient of concentrated dyes. The solution to be analyzed is placed between a
      glass slide and a spherical lens of known radius. The absorption coefficient is
      determined from attenuation of transmitted intensity as a function of the
      distance to the centre. At the same time, the interference pattern in the
      reflected image allows measurement of the refractive index of the dye.

PMID- 18638200
TI  - Total internal reflection microscopy for live imaging of cellular uptake of sub
      micron non-fluorescent particles.
AB  - This paper presents a simple, high-resolution, non-fluorescent imaging technique
      called total internal reflection microscopy (TIRM) and demonstrates its potential
      application to real-time imaging of live cellular events. In addition, a novel
      instrument is introduced that combines the simplicity of TIRM with the
      specificity afforded by dual-colour total internal reflection fluorescence (TIRF)
      microscopy and allows sequential imaging with the two modalities. The key design
      considerations necessary to apply these imaging modes in a single instrument are
      discussed. The application of TIRM alone yielded high-resolution live images of
      cell adherence to a poly-L-lysine modified substrate, whereby fine cellular
      structures are imaged. Non-fluorescent imaging of the uptake of sub-micron-sized
      polymeric particles by live cells is also demonstrated. Finally, images of
      fluorescently labelled cells were obtained in TIRF mode, sequentially to images
      obtained of the same cell in TIRM mode. Visual information gained using TIRF is
      compared with TIRM to demonstrate that the level of cell structure information
      obtainable with our total internal reflection microscope is comparable with the
      TIRF technique.

PMID- 18638201
TI  - Climbing the steps of viral atomic force microscopy: visualization of Dengue
      virus particles.
AB  - In recent years, the application of atomic force microscopy (AFM) to biological
      systems has highlighted the potential of this technology. AFM provides insights
      into studies of biological structures and interactions and can also identify and
      characterize a large panel of pathogens, including viruses. The Flaviviridae
      family contains a number of viruses that are important human and animal
      pathogens. Among them, Dengue virus causes epidemics with fatal outcomes mainly
      in the tropics. In this study, Dengue virus is visualized for the first time
      using the in air AFM technique. Images were obtained from a potassium-tartrate
      gradient-purified virus. This study enhances the application of AFM as a novel
      tool for the visualization and characterization of virus particles. Because
      flavivirus members are closely related, studies of the morphologic structure of
      the Dengue virus can reveal strategies that may be useful to identify and study
      other important viruses in the family, including the West Nile virus.

PMID- 18638202
TI  - A simple technique to minimize heat damage to specimens during thermal
      polymerization of LR White in plastic and gelatin capsules.
AB  - London Resin (LR) White is a commonly used resin for embedding specimens to be
      used for immuno- and/or cytochemical studies. In some instances, due to either
      the properties of the specimen or the availability of various reagents and
      equipment, it becomes necessary and/or more convenient to polymerize LR White
      using heat rather than chemical accelerators or UV light. It is known, however,
      that heat can reduce or even eliminate the anti genicity of the tissue being
      embedded. It is therefore desirable to polymerize specimens at the lowest
      temperature possible and to remove the specimens from the oven as soon as
      polymerization is complete. We have developed a technique that provides a visual
      marker that allows the exothermic polymerization of LR White to be monitored,
      thus minimizing the amount of time a specimen must stay in the oven while
      excluding oxygen from capsules of polymerizing LR White.

PMID- 18638203
TI  - Developing more positive attitudes towards mental health nursing in undergraduate
      students: part 1--does more theory help?
AB  - Negative attitudes towards mental illness and the mental health nursing
      profession have deterred many undergraduate nursing students from considering
      this area as an attractive career option. Positive clinical experience has been
      identified as the most important factor in producing more favourable attitudes.
      While the quantity of theory is identified as important, its impact on attitudes
      has not been examined through research. This study compared two groups of
      students undertaking different numbers of theoretical and clinical hours in
      mental health nursing to determine if this increase has an impact on nursing
      students' attitudes. Anonymous questionnaires were distributed to the total
      population of students following completion of the theoretical component of the
      programme but prior to clinical experience. The questionnaire was designed to
      assess: (1) nursing student's preparedness for and attitudes towards the mental
      health field; (2) consumers of mental health services; and (3) the students'
      career preferences. This first paper in a two-part series examines the impact of
      theoretical hours and suggests that while other attitudes are fairly similar
      between the two groups, the group exposed to more theory exhibited significantly
      more positive attitudes towards psychiatric nursing as a career.

PMID- 18638204
TI  - The experiences and perceived changes of Chinese ex-mental patients attending a
      holistic psychiatric rehabilitation programme: a qualitative study.
AB  - The paper reports a study on the subjective experiences and perceived personal
      changes of Chinese ex-mental patients attending a psychiatric holistic
      rehabilitation programme. The programme adopted a self-help group approach in
      which holistic aspects of physical, psycho-social and spiritual needs are
      emphasized. There are different rehabilitation programmes for chronic mental
      patients. However, spiritual element is not consciously included in most of these
      programmes. Furthermore, few studies document the changes of participants
      attending psychiatric rehabilitation adopting self-help and holistic care
      principles. A qualitative approach using an in-depth interview was adopted. A
      total of 20 members from the programme, which was about one-sixth of all the
      regular group members were recruited. All interviews were audiotaped and
      transcribed. Data were coded, categorized and developed to different themes using
      content analysis. Totally, there were 52 themes developed from the data. However,
      only 13 themes on experiences in the group and nine themes on the perceived
      personal changes were reported. By attending the programme, participants had
      positive feelings and gained many positive learning opportunities when
      interacting with peers. Interacting with group counsellors was also very
      beneficial to them. Though there were only some improvements physically, there
      were clear perceived positive changes in the psychological, social and spiritual
      dimensions. These findings are consistent with those found in the quantitative
      measures reported previously. The subjective experiences of the participants were
      positive and they perceived positive personal changes after joining the group.
      The findings support the effectiveness of the long-term nature of self-help
      group. Furthermore, the holistic programme helps members rediscover meaning and
      purpose of life and the religious practices in the group can be regarded to be a
      protective factor to stress not only to those believers but also to the non
      believers.

PMID- 18638205
TI  - A prospective study of patients absconding from a general hospital psychiatry
      unit in a developing country.
AB  - Characteristics of patients absconding from an open psychiatry ward in a
      developing country may be different from both those in developed countries and a
      mental hospital setting. The aim of this paper is to study the incidence and
      characteristics of patients absconding from an open psychiatric ward in a general
      hospital-based psychiatric unit in India. We studied patients consecutively
      admitted to an open psychiatric ward over a 2-month period. We compared those who
      absconded with those who did not. Out of 231 patients admitted, 33 absconded.
      Among those who absconded, 15 had bipolar disorder, 11 had schizophrenia and five
      had substance-related disorders. Nine had indicated their intention to do so at
      admission. Ten patients had absconded by the second day. The treatment cost was
      the likely influencing factor for seven patients who absconded after deemed fit
      for discharge on clinical grounds. Only 10 patients were readmitted to the
      hospital within 2 weeks of absconding. The risk of absconding is highest in the
      early days following. Absconding patients did not differ significantly from
      others in many socio-demographic and clinical features. Treatment costs are an
      important consideration in India.

PMID- 18638206
TI  - Perceived sleep quality of psychiatric patients.
AB  - This paper aims at acquiring knowledge about the quality of sleep of adult and
      elderly psychiatric patients who receive clinical or outpatient nursing care, and
      identifying key factors in perceiving a sleep problem. To do so, a sample of 1699
      psychiatric patients were asked whether they perceived a sleep problem and were
      invited to fill in the Pittsburgh Sleep Quality Index (PSQI) and additional
      questions. Five hundred and sixty (33%) questionnaires were returned. As a
      result, we find that 36% of the patients perceived a sleep problem, while the
      PSQI assessed 66% of the sample as being 'bad sleepers'. Forty-nine per cent of
      the respondents used sleep medication one or more times a week. Five items of the
      PSQI were shown to be predictors of a perceived sleep problem. Four of these are
      insomnia symptoms, while the fifth is the use of sleep medication. Moreover, the
      patients who used sleep medication most scored significantly worse on all PSQI
      components than patients who used sleep medication less than once a week. In
      conclusion, many psychiatric patients perceive a sleep problem and all nurses
      could be confronted not only with the night-time consequences of this, but also
      with daytime consequences. Therefore, sleep problems must not be viewed as an
      isolated problem but must be seen in relation with social functioning.

PMID- 18638207
TI  - Quantitative analysis of mental health nurse prescribers in Scotland.
AB  - The UK parliament approved legislation expanding prescribing rights for all
      registered nurses in 2006. Mental health nurses do not appear to be embracing
      prescribing to the same degree as their colleagues. For example, mental health
      nurses represent 14% of the UK nursing population, but only 3% nurse prescribing
      population. In order to explore this disparity, the paper discusses quantitative
      analysis of the following objectives: (1) describe the impact of nurse
      prescribing on nurse prescribers in NHS Greater Glasgow and Clyde; and (2)
      identify differences between mental health nurse prescribers and other nurse
      prescribers in NHS Greater Glasgow and Clyde. Following online pilot study, a 26
      item questionnaire was posted to 668 nurse prescribers in NHS Greater Glasgow and
      Clyde. A total of 365 questionnaires were returned (55.4%). Significant
      differences were found between mental health nurse prescribers and others in
      terms of age, gender, prescribing practice, academic achievement, method of
      prescribing, workplace, experience and attitude to prescribing. Possible reasons
      for these differences are suggested and form the basis of further planned
      research.

PMID- 18638208
TI  - The compatibility of psychosocial interventions (PSI) and assertive outreach: a
      survey of managers and PSI-trained staff working in UK assertive outreach teams.
AB  - In recent years, there has been an increased emphasis on providing psychosocial
      interventions (PSI) and assertive outreach (AO) for people with severe and
      enduring mental illness living in the UK. This paper presents the findings of a
      telephone survey conducted with managers and PSI-trained staff working for AO
      teams in the Northwest of England. The aim of the study was to gain an insight
      into staff attitudes regarding the compatibility of PSI and AO. The survey also
      gathered more general information about the nature of the AO teams and the number
      of PSI-trained staff working within them. The results indicate that, although PSI
      trained staff believe that PSI and AO are compatible, AO is not immune to the
      barriers to PSI implementation that exist in other service areas. There also
      appears to be a question regarding the extent to which teams are maintaining
      fidelity to the original AO model that was outlined by Stein and Test.

PMID- 18638210
TI  - Patient aggression in clinical psychiatry: perceptions of mental health nurses.
AB  - Mental health nurses are faced with an increasing number of aggressive incidents
      during their daily practice. The coercive intervention of seclusion is often used
      to manage patient aggression in the Netherlands. However, GGZ Nederland, the
      Dutch association of service providers for mental health and addition care, has
      initiated a project to decrease the number of seclusions in clinical psychiatry.
      A first step in this project is to gain insight into the current situation: the
      perceived prevalence of patient aggression, the attitudes of mental health nurses
      towards patient aggression and those socio-demographic and psychosocial factors
      that contribute to the use of coercive interventions. A survey was undertaken
      among 113 nurses from six closed and semi-closed wards. In this survey, two
      questionnaires were used: (1) the Attitude Toward Aggression Scale; and (2) the
      Perceptions of the Prevalence of Aggression Scale. Variables derived from the
      Theory of Planned Behaviour were also measured. Nurses reported being regularly
      confronted with aggression in general and mostly with non-threatening verbal
      aggression. They perceived patient aggression as being destructive or offensive
      and not serving a protective or communicative function. The nurses generally
      perceived themselves as having control over patient behaviour (i.e. considerable
      self-efficacy) and reported considerable social support from colleagues. Although
      the nurses in this study were frequently confronted with aggression, they did not
      experience the aggression as a major problem.

PMID- 18638209
TI  - Caregivers' reflections on their interactions with adult people with learning
      disabilities.
AB  - People with learning disabilities and their professional carers often have
      difficulty interacting. The aim of this study was to illuminate carers'
      reflections on their interactions with adult people with learning disabilities.
      In a previous study, interactions between 16 carers and 11 residents with
      learning disabilities were recorded on video. In this study, stimulated recall
      interviews about the interactions were carried out with all the carers. The text
      was analysed using qualitative content analysis. The findings indicate that the
      carers reflected on both successful and unsuccessful interaction. Examples of
      successful interaction included understanding cues, satisfying needs, and
      managing challenging behaviours, and the carers reflected on the influences that
      successful interaction had on security, confidence, and satisfaction among the
      residents. Examples of unsuccessful interaction included failing to understand
      cues, failing to satisfy needs and failing to manage challenging behaviours, and
      the carers reflected on the consequences of such interaction, which included
      irritation, aggression and violence among the residents. Our findings have
      implications for interventions aimed at strengthening the competence of carers
      and developing strategies for managing challenging behaviour, in order to ensure
      high-quality care and a good working climate.

PMID- 18638211
TI  - An examination of the services provided by Psychiatric Consultation Liaison
      Nurses in a general hospital.
AB  - The political, professional and economic context in which mental health care is
      delivered has witnessed significant changes in recent times. The movement of
      psychiatric patients from institutions to community settings has seen the
      emphasis of the loci of care delivery shifting with increasing numbers presenting
      to general hospitals. The speciality of the Psychiatric Consultation Liaison
      Nurse (PCLN) has emerged as a bridge between mental health and general hospital
      services. A descriptive, non-experimental research approach was employed to
      establish patient profiles and to provide an overview of the depth of service
      provision. This design was selected as the most appropriate because of the
      limited information on the PCLN in an Irish setting and secondly, as the study
      was limited to one rural geographical location. A questionnaire was utilized to
      collate the details of patients who had received a mental health assessment. The
      findings presented here are the profiles of patients assessed by the PCLN during
      the 3-month study period. The results add further credence to the existing
      evaluative studies in presenting the characteristics of patients within the Irish
      context and further contribute to the unique body of evidence that defines the
      mental health nurse in an advancing role.

PMID- 18638212
TI  - Revisiting the slave trade: owning our pasts.

PMID- 18638213
TI  - Do 'no-suicide' contracts work?
AB  - Suicide is the main cause of premature death in mental health service users, and
      the prevention of suicide is a major, global concern. An intervention designed to
      address this concern is the 'no-suicide' contract (NSC) - an agreement, usually
      written, between a mental health service user and clinician, whereby the service
      user pledges not to harm himself or herself. Following a review of the literature
      on NSCs, this paper argues that there is a lack of quantitative evidence to
      support such contracts as clinically effective tools and that there is strong
      opposition to the tool, from both service users and nurses. Moreover, important
      ethical and conceptual issues in the use of such contracts have been identified,
      including the potential for coercion from the clinician for their own protection
      and the ethical implications of restricting a service user's choices when they
      may be already struggling for control. In light of these findings, the paper
      discusses alternative interventions aimed at preventing self-harm and suicide.
      Although a number of other interventions are available to clinicians, further
      research is required to test the effectiveness of these as viable alternatives to
      the NSC.

PMID- 18638218
TI  - Systemic therapy of paediatric atopic dermatitis: an update.
AB  - Topical therapies are the mainstay in the treatment of atopic dermatitis, and are
      effective in the majority of patients with mild and localized disease. In
      patients with widespread or recalcitrant moderate to severe dermatitis, systemic
      therapies may be required. The frequently used systemic therapies are
      immunosuppressants, immune response modifiers, anti-inflammatories,
      antihistamines, and antibiotics. In this article, the indications and scientific
      support for the use of these medications is reviewed.

PMID- 18638220
TI  - Autoantibodies to basement membrane proteins BP180 and BP230 are commonly
      detected in normal subjects by immunoblotting.
AB  - Autoantibodies to basement membrane proteins BP180 and BP230 are characteristic
      of bullous pemphigoid and other subepidermal immunobullous disorders. These
      antibodies are, however, reported in other pruritic dermatoses, non-bullous
      disorders and non-cutaneous disease. Few studies have assessed basement membrane
      antibodies in normal subjects; antibody prevalence in this population is not
      clear. This study aims to examine basement membrane zone antibodies in normal
      middle-aged to elderly subjects. Sera from 61 healthy subjects (majority age 50
      70 years) were assessed by immunoblot, indirect immunofluorescence and enzyme
      linked immunosorbent assay. Ninety-one bullous pemphigoid patients acted as
      positive controls. Antigenic target, antibody class and titre were examined; sera
      binding BP180 were assessed for reactivity to the non-collagenous 16A (NC16A)
      domain. Thirty-six normal subjects (59%) had antibodies to either BP180 or BP230
      on immunoblot analysis. BP180 was the commonest target antigen, detected in 35
      subjects; binding to the immunodominant NC16A domain was not detected.
      Immunofluorescence was positive in three subjects. Of the bullous pemphigoid
      sera, 88% were positive on immunoblot or immunofluorescence; a higher frequency
      had antibodies against BP230. In conclusion, significant numbers of normal
      healthy subjects have circulating autoantibodies to basement membrane proteins,
      chiefly BP180 detectable by immunoblot, but these do not bind the NC16A domain.

PMID- 18638221
TI  - Knowledge and perceptions about sunburn and solar keratoses in Australia.
AB  - An omnibus telephone survey of 1200 adult Australians determined self-reported
      prevalence of and attitudes to sunburn and sunspots, knowledge of the term solar
      keratosis and prevalence of skin checks. Half reported they had been sunburnt in
      the previous year. Seventy-eight per cent considered sunburn to be extremely or
      very serious, while 73% considered sunspots as serious or very serious. While 29%
      reported currently having sunspots, 69% had never heard of the term solar
      keratosis, 30% had never had a skin check and 28% had their last skin check more
      than 12 months ago. Respondents 18-29 years old (odds ration [OR] = 2.6; P =
      0.002) and men (OR = 2.4; P < 0.001) were most likely to experience multiple
      sunburn. Persons living in capital cities (OR = 0.63; P = 0.006) and having a
      university degree (OR = 0.52; P = 0.001) had reduced OR for multiple sunburns.
      Men (OR = 0.45; P < 0.001) were less likely to consider sunburn serious or
      extremely serious than women. Compared with respondents 18-29 years old, those 55
      years or older were 7.4-fold more likely to have had a skin check (P < 0.001).
      Sun-protection campaigns need to continue using evidence-based interventions
      targeting younger people and men to reduce sunburn. The terms used in health
      promotion need to be understood by the target audience.

PMID- 18638222
TI  - Black heel, talon noir or calcaneal petechiae?
AB  - We describe a series of six patients with superficial cutaneous haemorrhages of
      the feet, including a classical case of black heel (talon noir) and other similar
      cases with diverse clinical presentations that do not match the typical
      description of that process. The main differences lay in production mechanism,
      morphology and location. The causes of these 'atypical' lesions were: burns with
      hot sand, friction against the rough edge of a swimming pool, wearing new shoes,
      jogging, or pricking a blister with a needle. Clinically, they consisted of
      isolated or multiple, small, large or linear, brown or black lesions located in
      areas that did not include the convex part of the heel, in which talon noir
      usually appears; on the contrary, the lesions affected the back third of the
      soles, the toes, periungual fold and plantar arch. As the presence of blood in
      the horny layer was a common final factor in all these cases, a better name for
      this process would be 'post-traumatic cutaneous intracorneal blood' to describe
      black heel and its diverse clinical presentations.

PMID- 18638223
TI  - From biologic to biologic to biologic: lessons to learn for erythrodermic and
      recalcitrant chronic plaque psoriasis.
AB  - Differences in mode of action between biologic agents could explain why one agent
      is more efficacious than another in the treatment of recalcitrant and
      erythrodermic flares of chronic plaque psoriasis. Here, we present our experience
      using a case series of three patients with chronic plaque psoriasis who showed
      consistent and similar responses to three different biologic agents. All three
      patients who were refractory to efalizumab developed erythrodermic flares 2-12
      weeks after a direct switch to etanercept. Switching from efalizumab to
      etanercept could provoke paradoxical flaring of psoriasis, which might be
      prevented by transitioning to systemic agents. The erythrodermic flares in all
      three patients responded dramatically to infliximab with marked and maintained
      improvements in Psoriasis Area and Severity Index scores.

PMID- 18638224
TI  - Erythema induratum in a Kenyan child.
AB  - A 10-year-old Kenyan girl presented with a 9-month history of a persistent,
      painful eruption of multiple, tender, non-ulcerated, pigmented nodules involving
      the calves, shins and soles of the feet. She had recurring fevers particularly at
      night, lethargy, weight loss and a persistent non-productive cough. The Mantoux
      test was positive. Chest X-ray revealed mild peribronchial thickening in the
      hilar region but no evidence of hilar lymphadenopathy, consolidation and/or
      cavitation suggestive of tuberculosis. Sputum and gastric washings were negative
      for acid-fast bacilli. Histology on a skin biopsy showed a granulomatous
      panniculitis with no histological evidence of Mycobacterium tuberculosis,
      consistent with erythema induratum. In view of her constitutional symptoms,
      chronic non-productive cough and positive Mantoux test, she was diagnosed with
      pulmonary tuberculosis despite the non-specific chest X-ray and negative
      bacteriology. Anti-tuberculous therapy was initiated with pyrazinamide, isoniazid
      and rifampicin for 2 months followed by dual therapy with isoniazid and
      rifampicin for a further 4 months. Her constitutional and respiratory symptoms
      and skin eruption cleared within 6 months with treatment.

PMID- 18638225
TI  - Eosinophilic annular erythema: a subset of Wells' syndrome or a distinct entity?
AB  - A 52-year-old woman with a 6-year history of a persistent non-pruritic cutaneous
      annular eruption, forming polycyclic and arcuate plaques that commenced as
      erythematous papules and nodules, is presented. Lethargy and arthralgia were
      associated symptoms. We have followed this patient for the last 3 years, and
      during this period she has continued to have a florid annular eruption of unknown
      cause. Laboratory tests, including an eosinophil count, examination of stool
      samples for parasites, and a computed tomography scan of the chest, abdomen and
      pelvis, failed to detect any abnormalities. Skin biopsies demonstrated a
      superficial to deep cellular infiltrate consisting of numerous eosinophils, with
      lymphocytes and isolated neutrophils. Eosinophilic dust, flame figures and
      granulomatous inflammation were not seen. In addition, strands of mucin were
      present through the dermis, and prominent basal vacuolar change was evident at
      the dermoepidermal junction; these features may represent new findings that help
      define a distinct form of eosinophilic annular erythema.

PMID- 18638226
TI  - Spontaneous resolution of facial papular mucinosis in a transplant patient.
AB  - A 37-year-old male developed facial papules 6 months post renal-pancreatic
      transplant. Histological findings were consistent with localized papular
      mucinosis; electrophoresis showed no paraprotein. A trial of erbium and aura
      lasers, at ablative doses, produced no improvement. Independent treatments with
      oral doxycycline, itraconazole, acitretin, and isotretinoin also had no effect.
      The facial papules improved spontaneously, 2 years after first presentation and 8
      months after treatment ceased. The patient remains clear of lesions.

PMID- 18638227
TI  - Poliosis circumscripta associated with neurofibromatosis 1.
AB  - A 38-year-old man presented with axillary freckling, multiple cafe au lait
      macules and neurofibromas on the scalp, trunk and extremities. In addition, he
      had a patch of white hair on the right parieto-occipital area overlying a scalp
      neurofibroma. He was diagnosed with poliosis circumscripta associated with
      neurofibromatosis 1.

PMID- 18638228
TI  - Histopathological evolution of a cutaneous myxofibrosarcoma.
AB  - A 54-year-old woman presented with a 6-month history of a tender and swollen
      plaque appearing as a panniculitis affecting the left pretibial area. The initial
      histopathology revealed dermal and subcutaneous inflammation with interstitial
      histiocytes and mucinosis suggestive of either granuloma annulare or necrobiosis
      lipoidica. Over the subsequent 6 months the plaque grew progressively, despite
      treatment with topical corticosteroids under occlusion. Distal to the plaque
      reduced sensation developed in the limb. Biopsies of the nodular areas now
      revealed a dense dermal infiltrate of atypical spindle cells within a prominent
      myxoid stroma and a pleomorphic multinucleated epithelioid cell component. These
      features were those of an intermediate grade myxofibrosarcoma. This soft-tissue
      sarcoma may initially masquerade clinically as a panniculitis and a granulomatous
      process on biopsy as in our patient, leading to a delay in surgical therapy.

PMID- 18638229
TI  - Successful response to narrow-band UVB in a patient undergoing concomitant
      treatment with adalimumab for psoriasis.

PMID- 18638234
TI  - What happened in Finland to increase home hemodialysis?
AB  - Finland is geographically a rather large country with a relatively sparse
      population (5.3 million). Home hemodialysis (HHD) was started in Helsinki 40
      years ago and in the early years it was only used in selected patients. However,
      by the late 1980s HHD almost disappeared owing to the advent of CAPD and new HD
      centers. Towards the end of the 1990s, it became evident that PD had limitations
      and new ways had to be found to individualize HD, improve the outcome, increase
      capacity, and limit the growth of costs of HD. After careful planning, HHD was
      reinstituted at the Helsinki University Hospital in 1998 and since then the
      program has grown steadily. By December 31, 2007, altogether 163 patients had
      started at home. This has required changes in the predialysis program where the
      "home first" policy was adopted. Other important features include close
      cooperation with other nephrological centers as well as centralized HHD training
      that also supports more remote hospitals. Since then this therapy has been
      started in several other academic and in some smaller hospitals, and at the end
      of last year about 4% of all Finnish dialysis patients (n=1.600) were on HHD
      (prevalence 11.8/million). In the Helsinki metropolitan area this treatment is
      the most economical modality (estimated annual global costs euro37.000),
      comparable to self-care satellite HD and CAPD. A successful HHD program requires
      a well-organized predialysis program, a highly motivated multidisciplinary team,
      and well-developed training networks.

PMID- 18638235
TI  - The advantages and disadvantages of home hemodialysis.
AB  - In Australia, 12% of the hemodialysis population dialyze at home. Until recently,
      the majority of these patients dialyzed for similar hours to those in satellite
      dialysis. However, in the past 5 years there has been a new departure such that
      in many centers the concept of home hemodialysis is now synonymous with extended
      hours dialysis. Registry data supports the concept that increased frequency and
      duration of dialysis may result in improved patient survival and a reduction in
      cardiovascular risk profile. It is hoped, therefore, that the long recognized
      survival benefit observed in home hemodialysis patients may be further augmented
      by the swing to extended hours dialysis in this patient population. In addition
      to the physiological benefits of extended hours home dialysis, there are clear
      quality of life, social, and economic advantages associated with dialyzing at
      home. There are however a number of perceived disadvantages to home hemodialysis
      including the application and time commitment required for training, the
      potential for relationship strain or "burnout," and reluctance to "hospitalize"
      the home. Overall, however, in this new era of extended hours dialysis, the
      advantages both physiological and lifestyle of home hemodialysis far outweigh the
      disadvantages.

PMID- 18638236
TI  - The renaissance of home hemodialysis: where we are, why we got here, what is
      happening in the United States and elsewhere.
AB  - Home hemodialysis has been around since 1964, but its use has declined over the
      years in most countries, this despite its advantages, particularly improved
      patient survival and quality of life and significant cost savings. Experience has
      shown that home hemodialysis can be performed successfully by many more patients
      than at present. Recently, with the demonstration of even better results with
      more frequent hemodialysis that is obviously best performed at home and with the
      development of new, more patient-friendly machines, the use of home hemodialysis
      is beginning to increase again.

PMID- 18638237
TI  - Complications of home hemodialysis.
AB  - Home hemodialysis is regaining popularity as a treatment choice for end-stage
      kidney disease. This trend is fueled by numerous reports of better survival and
      improved quality of life with primarily home-based more frequent and/or longer
      hours of hemodialysis. Home hemodialysis in the contemporary era is generally
      very safe. Advances in machine technology have reduced technical complications
      and longer and more frequent treatments have reduced the risk of hypotension and
      cardiovascular instability. A successful home hemodialysis program must focus on
      patient safety to prevent serious hemorrhage from needle dislodgement and enable
      an aseptic cannulation technique. In addition, vigilance in relation to machine
      maintenance procedures and attention to water quality are key skills that
      patients must acquire for optimal outcomes. The possibility of increased septic
      events with longer and more frequent hemodialysis regimens performed in the home,
      the long-term psychosocial effects of home hemodialysis, and the best methods for
      maintaining compliance of patients in the long term are of particular
      contemporary interest.

PMID- 18638238
TI  - Home hemodialysis in Australia and New Zealand: practical problems and solutions.
AB  - Home hemodialysis, as practiced in Australia and New Zealand, offers patients the
      return of self-control and self-esteem. It also allows reconnection with family,
      friends and (re)employment. Though there are emotional and time-related "costs"
      with home hemodialysis, these center on training time, commitment and patient or
      family stresses and, if carefully managed and properly resourced, can be overcome
      for most home-suitable patients. As we believe many center-based hemodialysis
      patients are home-suitable and that home care is severely under-utilized,
      assessment techniques to maximize uptake are examined. While patient dropout from
      home care relates more to staff attitudes than to true home-failure, dropout is
      minimized by ensuring the patient and not a carer takes full dialysis
      responsibility with the carer acting as a supporter and not the facilitator.
      Installation of home equipment is simple and cheap, the financial costs of home
      hemodialysis being substantially less than those of facility care where salary
      and infrastructure costs far exceed training, equipment, installation and
      maintenance costs at home. Home monitoring is not routinely required especially
      with longer, more frequent regimens-but effective 24-hour on-call nurse and
      technician cover is essential. Intravenous drug self-administration at home is
      safe and effective, reducing the need for hospital visits to a 2-3 monthly
      minimum. The debilitating effects of facility care cannot be over-emphasized
      while the liberating psychology of a well-supported hemodialysis program is truly
      satisfying for patient and staff alike.

PMID- 18638239
TI  - The ideal home hemodialysis machine.
AB  - Daily home hemodialysis (HD) patients have a much superior survival rate than
      patients on regular, 3 times a week in-center HD or on peritoneal dialysis.
      Present-day HD machines are unsuitable for use at home by patients. We present
      our concept of the ideal home HD machine that allows daily short and long HD,
      does all the work preparing for and cleaning up after dialysis, has an
      intravenous infusion system controlled by the patient, needs no systemic
      anticoagulation, and teaches and interacts with the patient during dialysis. To
      fulfill these functionalities, the dialyzer and blood tubing must be integrated
      with the machine and replaced less often than monthly, the machine must be
      capable of at least 200 L/week of hemodiafiltration, prepare all fluids necessary
      between and during dialyses, and all the components and fluids must be much
      beyond ultrapure.

PMID- 18638240
TI  - Toward the wearable artificial kidney.
AB  - The evolution of technology in hemodialysis has gone through several steps
      including the feasibility phase, the search for reliability, the implementation
      of automation to improve efficiency and the quest towards increased tolerance and
      treatment adequacy. Today, a new challenge is appearing on the scene and it
      concerns miniaturization, transportability, wearability and the possibility of
      developing implantable devices for renal replacement therapies. Although we are
      not there yet, a new series of papers have recently been published disclosing
      interesting and promising results on the application of wearable ultrafiltration
      systems (WUF) and wearable artificial kidneys (WAK). Some of these use
      extracorporeal blood cleansing as a method of blood purification while others use
      peritoneal dialysis as a treatment modality. This manuscript presents the initial
      results with these new devices and proposes an effort to make a quantum leap in
      technology making the wearable artificial kidney a reality rather than a dream.

PMID- 18638241
TI  - Short and long nightly hemodialysis in the United States.
AB  - When hemodialysis first started in the United States in the 1960s, a large
      percentage of patients performed their treatments at home. However, because of
      reimbursement issues, home hemodialysis (HHD) gradually succumbed to an in-center
      approach and eventually a mindset. Since the introduction of nightly HHD by
      Uldall and Pierratos in 1993, there has been a resurgence of interest in HHD.
      This paper describes the different types of home hemodialysis being performed as
      of December 31, 2007 in this country. Because neither the United States Renal
      Data System (USRDS) nor the End Stage Renal Disease (ESRD) Networks break down
      home dialysis into the different modalities, a provider questionnaire was sent
      out to 2 major providers, a number of mid-level providers and other providers
      known to do HHD. In addition, a questionnaire was sent out to 3 machine providers
      to obtain the number of patients using their machine for HHD as of December 31,
      2007. The results showed that 91.7% of patients are dialyzing in-center, 7.3% are
      doing peritoneal dialysis, and 0.7% are doing HHD. Currently about 1% of ESRD
      patients in the United States are doing home hemodialysis. NxStage, however, has
      started 1000 patients in the past year on short-daily home hemodialysis. Patients
      are beginning to understand that there are better options than 3 times a week in
      center dialysis. And as a result of the "HEMO Study," nephrologists now believe
      that longer and more frequent dialysis is a better therapy for ESRD patients.
      Therefore, promotion of HHD should become a priority for the renal community in
      the future.

PMID- 18638242
TI  - Role of peritoneal dialysis in the era of the resurgence of home hemodialysis.
AB  - In recent years, there has been a resurgence of home hemodialysis (HHD)
      therapies. Given the small percentage of prevalent patients in the United States
      currently on home dialysis, an appropriate question is: What is the role of
      peritoneal dialysis (PD) in this era? Data suggest that in centers that are
      promoting the growth of HHD, their PD programs also tend to be very active.
      Furthermore, our experience and other data suggest that one should not worry
      about cannibalizing PD in order to grow HHD. Most HHD patients come from in
      center hemodialysis or those patients transitioning from PD to another therapy.
      In fact, data suggest that in order to promote the growth of HHD, a certain
      minimal infrastructure is needed in terms of staff. An active PD program not only
      supports a robust infrastructure that allows for HHD growth but also fosters
      profitability of a home program.

PMID- 18638243
TI  - What limits the expansion of self-care dialysis at home?
AB  - Self-care dialysis at home, whether peritoneal dialysis or hemodialysis, is more
      cost-effective than in-center dialysis and treatment outcome is at least
      comparable. Still, both self-care modalities are considered underutilized and we
      wished to identify the perceived reasons for this underutilization among
      nephrology professionals. A questionnaire was distributed at 5 international
      nephrology meetings in 2006. Questions addressed the most important stakeholders
      and the most important issues for patients and nephrology professionals to enable
      the expansion of self-care dialysis and commonly mentioned barriers were given as
      alternative responses. The proportion of patients considered suitable for self
      care was also investigated. Seven thousand responses were collected. The listed
      stakeholders, i.e., health care and reimbursement authorities, nurses and
      physicians, and finally patients and their families, are considered approximately
      equally important for the process. Nephrology professionals feel that patient
      motivation for choosing and performing self-care dialysis is the strongest
      driver. The need for dedicated resources for self-care is judged to be vital for
      the expansion of this modality of treatment. Thirty-two percent of incident
      patients are considered able to perform self-care dialysis at home. This
      international survey among 7000 nephrology professionals has identified patient
      motivation as one of the strongest drivers of self-care dialysis at home. The
      need for dedicated resources for the staff to devote time to developing such
      motivation is given as one of the major reasons for the slow adoption. Under
      ideal conditions, it is felt that one-third of all patients starting dialysis can
      be trained to perform self-care dialysis.

PMID- 18638244
TI  - Home hemodialysis in Australia: current perspective.
AB  - Home hemodialysis (HD) in Australia represents 11% of the dialysis population.
      This percentage has declined over the last 20 years but the absolute number of
      home HD patients has increased since 2001. The major reason for this resurgence
      has been the institution of nocturnal HD at home. Predominantly, this has been as
      a strictly alternate day exercise, although 5-6 times per week dialysis is also
      practised. Short-daily HD is uncommon in Australia. Nocturnal HD now comprises
      30% or more of all home HD. Most home HD in Australia is practiced without remote
      monitoring, using simple machines with separate reverse osmosis units. Patients
      tend to self-needle and not all have a "partner." The enthusiasm for nocturnal HD
      in particular has been fuelled by ANZDATA Registry data demonstrating a survival
      advantage for patients dialyzing alternate days compared with 3 times per week;
      and for patients dialyzing for >18 hours per week compared with 12 or 15 hours
      per week.

PMID- 18638245
TI  - The International Quotidian Hemodialysis Registry: rationale and challenges.
AB  - Outcomes from conventional thrice-weekly hemodialysis (CHD) are disappointing for
      a life-saving therapy. The results of the HEMO Study show that the recommended
      minimum dose (Kt/V) for adequacy is also the optimum attainable with CHD.
      Interest is therefore turning to alternative therapies exploring the effects of
      increased frequency and time of hemodialysis (HD) treatment. The National
      Institutes of Health have sponsored 2 randomized prospective trials comparing
      short hours daily in-center HD and long hours slow nightly home HD with CHD. An
      International Registry has also been created to capture observational data on
      patients receiving short hours daily in-center HD, long hours slow nightly home
      HD, and other alternative therapies. Participation by individual centers, other
      registries and the major dialysis chains is growing and currently data from
      nearly 3000 patients have been collected. Pitfalls in data collection have been
      identified and are being corrected. A matched cohort (patients in other
      registries) study is planned to obtain information regarding hard outcomes
      expected from these therapies. The Registry may become the most important source
      of information required by governments, providers, and the nephrological
      community in assessing the utility of such therapies.

PMID- 18638246
TI  - James E. Cimino, M.D.: Recipient of the 2008 International Society for
      Hemodialysis Belding Scribner Trailblazer Award.

PMID- 18638247
TI  - A conversation between Belding Scribner & Jack Cimino.

PMID- 18638248
TI  - Abstracts of the XIXth International Congress on Fibrinolysis and Proteolysis.
      July 6-10, 2008, Vienna, Austria.

PMID- 18638251
TI  - Evaluation and quantification of nuclear DNA from human telogen hairs.
AB  - Nuclear DNA was extracted from human telogen hairs from 60 individuals. Six to
      nine hairs from each individual were individually extracted. The amount of DNA
      recovered from each individual varied greatly, and most samples yielded a
      quantity of 550 pg or less per hair. A selective extraction buffer was used to
      remove epithelial cell DNA and the amount of exogenous DNA was determined. DNA
      was also quantified by real time PCR using three different sized amplicons
      targeting an Alu sequence. The results were used to determine the state of
      degradation of the extracted DNA. Different quantities of sample (<100 pg, 100
      500 pg, >500 pg) were amplified with the Miniplex kits to determine the minimum
      DNA template required for successful amplification. DNA recovered from hair
      showed degradation; however, partial profiles were obtained for those samples
      containing at least 60 pg using MiniSTRs.

PMID- 18638252
TI  - Sequential unmasking: a means of minimizing observer effects in forensic DNA
      interpretation.

PMID- 18638253
TI  - Revisiting old cases of unidentified decedents: problems encountered, lessons
      learned, and suggestions for others.

PMID- 18638264
TI  - A review of fibroblast-populated collagen lattices.
AB  - Bell's introduction of the fibroblast-populated collagen lattice (FPCL) has
      facilitated the study of collagen-cell interactions. As a result of the numerous
      modifications of the casting of FPCLs, the in vivo applications of these in vitro
      findings have been confusing. Here experimental FPCL contraction findings are
      viewed in regard to three proposed mechanisms responsible for lattice
      contraction. The cellular mechanisms responsible for generating FPCL contraction
      are cell contraction, cell tractional forces related to cell locomotion, and
      initial cell elongation and spreading.

PMID- 18638265
TI  - Local therapy and treatment costs of chronic, venous leg ulcers with electrical
      stimulation (Dermapulse): a prospective, placebo controlled, double blind trial.
AB  - The purpose of our study was the evaluation of the therapeutic benefit and the
      economical profit of low-frequency pulsed current applied to therapy-resistant
      venous leg ulcers. We investigated 39 patients in a prospective, placebo
      controlled, double blind study on the effect of low-frequency pulsed current
      (Dermapulse) on healing in chronic venous ulcers during a 4-month course of
      treatment. All patients had chronic venous ulcers. The following criteria were
      recorded: ulcer size, pain, capillary density, and transcutaneous oxygen partial
      pressure. In verum group 3, ulcers healed and ulcer area was reduced
      significantly. In placebo group two ulcers healed. Ulcer size was reduced
      significantly in each group (paired test), the difference of ulcer area reduction
      between the "verum" and the placebo group (unpaired test) was not significant.
      Capillary density in the ulcer increased in both groups. In verum group,
      electrical stimulation led to rapid and lasting reduction of pain (unpaired test,
      p=0.049). By means of the process calculation method for the subgroup of
      outpatients this treatment method was economically effective. Electrical
      stimulation seems to be a viable treatment option for therapy-resistant venous
      leg ulcers.

PMID- 18638266
TI  - The role of topical negative pressure in wound repair: expression of biochemical
      markers in wound fluid during wound healing.
AB  - The clinical effects of topical negative pressure therapy (TNP) on wound healing
      are well described in numerous articles. While the mechanism(s) of action are not
      completely understood, it is postulated that reduction of local and interstitial
      tissue edema, increased perfusion of the (peri-) wound area, changed bacterial
      composition, and mechanical stimulation of the woundbed contribute to the
      clinical success. Our hypothesis is that with the removal of excessive fluid,
      proteolytic enzymes negatively influencing the healing process are removed. Our
      aim was to assess whether the concentrations of albumin, matrixmetalloproteinase
      9 (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) were different
      between wounds treated with TNP and conventional gauze therapy. We analyzed wound
      fluid samples of 33 wounds treated with either TNP therapy (n=15) or conventional
      therapy (n=18) on albumin, pro- and activated MMP-9, TIMP-1, and the ratio of
      total MMP-9/TIMP-1. Albumin levels were found to increase significantly in acute
      wounds compared with chronic wounds; however, no difference could be found on
      comparing TNP with conventional therapy. We did find significantly lower levels
      of pro-MMP-9 and lower total MMP-9/TIMP-1 ratio in TNP-treated wounds during the
      follow-up of 10 days. These data strongly suggest that TNP therapy influences the
      microenvironment of the wound.

PMID- 18638267
TI  - The altered expression of syndecan 4 in the uninvolved skin of venous leg ulcer
      patients may predispose to venous leg ulcer.
AB  - Syndecan 4 (SDC4), a heparan sulfate proteoglycan, and neuropilin 1 (NRP1), a
      transmembrane receptor, are both involved in normal wound healing, but little is
      known about their possible role in venous leg ulcer pathogenesis. We aimed to
      investigate whether there are any expression abnormalities and/or gene
      polymorphisms of SDC4 and NRP1 associated with venous leg ulcer. SDC4 showed
      significantly lower mRNA and protein expression in the uninvolved dermis of
      venous leg ulcer patients (n=15) compared with controls (n=15; p=0.0136), while
      NRP1 showed no expression abnormalities. None of the examined SDC4 and NRP1
      polymorphisms showed a difference in their allelic distribution between leg ulcer
      patients (n=92) and controls (n=92). We hypothesize that SDC4 may play an
      essential role not only in the inflammation and tissue formation phases of normal
      wound healing, but its expression abnormalities observed in the uninvolved dermis
      of venous leg ulcer patients may contribute to venous leg ulcer development.

PMID- 18638269
TI  - Initial healing rates as predictive factors of venous ulcer healing: the use of a
      laser-based three-dimensional ulcer measurement.
AB  - There is a need for practical methods to predict the healing time of venous leg
      ulcers. In a prospective cohort study of 81 patients with venous leg ulcers, we
      used a recently described laser-based three-dimensional measurement of the ulcers
      at days 0 and 28 to estimate the predictive power of horizontal (HIHR) and
      vertical initial healing rates (VIHR) for wound healing by week 24. The rates
      were calculated by Gilman's equation [(A(1)-A(2))/((p(1)+p(2))/2)((0-4))] and by
      its modification [(V(1)-V(2))/((A(1)+A(2))/2)((0-4))], respectively. The
      influence of risk factors on both the initial healing rates was also studied. The
      HIHR and VIHR are important predictors of healing at 24 weeks. They are not
      influenced by age, ulcer duration, initial ulcer area, and insufficient sapheno
      femoral junction, and/or calf perforating veins. Together with ulcer duration,
      they are independent predictors of the 24-week healing (the area under ROC curve
      equals to 0.9). VIHR gives us additional information and significantly improves
      the prediction of 24-week healing.

PMID- 18638268
TI  - Evaluation of dermal pericapillary fibrin cuffs in venous ulceration using
      confocal microscopy.
AB  - Dermal pericapillary fibrin is a hallmark of venous disease and is thought to
      play a pathogenic role in the development of ulceration. However, the actual
      spatial configuration of pericapillary fibrin is unknown, and it remains unclear
      whether it truly represents a barrier that can impair physiological exchanges
      between the blood and dermis. Using confocal microscopy on tissue specimens taken
      from the edges of venous ulcers in six patients, we report a detailed analysis of
      dermal pericapillary fibrin deposits. Sections were evaluated with an antibody to
      human fibrinogen/fibrin and viewed, vertically and horizontally, with confocal
      microscopy. The distribution of fibrin deposition was highly variable and patchy,
      with areas of great intensity next to others of marginal intensity. Vertical cut
      sections showed the highest concentration of fluorescent material next to the
      lumen of dermal capillaries. Horizontal sections showed that maximal fluorescence
      was distributed at random. Our findings indicate that fibrin deposits in venous
      ulcers are patchy and discontinuous around dermal vessels. As such, these
      deposits are unlikely to act as a true and stable anatomic barrier as originally
      proposed. However, pericapillary fibrin may still act as a physiological barrier
      under conditions of poor blood flow where even marginal or patchy fibrin
      deposition might have a greater effect on the exchange of oxygen and other
      nutrients between blood and dermis.

PMID- 18638270
TI  - Hyperbaric oxygen attenuates cell growth in skin fibroblasts cultured in a high
      glucose medium.
AB  - Hyperglycemia and hypoxia synergistically retard diabetic wound healing. We
      investigated the direct effect of hyperbaric and normobaric hyperoxia on skin
      fibroblasts cultured in a high-glucose medium. Detroit 551 human dermal
      fibroblasts cultured in Dulbecco's modified Eagle's medium containing d-glucose
      had reduced cell survival compared with cells grown in normal glucose medium;
      survival was 27.5+/-3.8% lower in 25 mM glucose and 30.6+/-3.7% lower in 50 mM
      glucose. Cell survival decreased because of inhibition of cell proliferation and
      enhanced cell death. Daily hyperbaric oxygen therapy at 2.5 atmosphere absolute
      for 90 minutes on 3 consecutive days reduced cell proliferation and increased
      cell death in normal cultured fibroblasts. Hyperbaric oxygen therapy and high
      glucose medium had a synergistic effect and reduced survival by 37.6+/-4.4% (25
      mM glucose) and 39.6+/-5.1% (50 mM glucose). The effects of hyperbaric oxygen and
      high-glucose medium were associated with overproduction of reactive oxygen
      species. Our results suggest that direct exposure of skin fibroblasts to
      hyperbaric oxygen affects cell growth and superimposes the toxic effect of high
      glucose. This cytotoxicity may be related to the production of reactive oxygen
      species in the fibroblasts.

PMID- 18638271
TI  - Healing of a porcine burn wound dressed with human and bovine amniotic membranes.
AB  - The effects of amniotic membranes (AMs), either fresh human and bovine AMs or
      acellular bovine AMs, on wound healing were compared among the burn wounds of
      porcine skin. Six pigs were chosen for the study, and we created deep second
      degree contact burns on them with a digitally controlled aluminum thermal block.
      Then we applied the dressings to some of the wounds using fresh human and bovine
      AMs, acellular bovine AMs, polyurethane foam, or no dressing. We evaluated the
      pigs for (1) the rate of epithelialization, (2) histological grading, and (3)
      infections. We found that the AM groups showed better wound-healing effects than
      did the polyurethane foam and no dressing groups, and these differences were
      statistically significant. However, the differences between the AM groups were
      not statistically significant. Wound cultures showed higher infection rates in
      the control and polyurethane foam groups compared with the other groups. Our
      study showed that fresh or acellular bovine AMs provided similar efficacy for
      wound healing as did the fresh human AMs.

PMID- 18638272
TI  - Topical substance P increases inflammatory cell density in genetically diabetic
      murine wounds.
AB  - The neuropeptide substance P (SP) is a known inflammatory mediator released from
      cutaneous peripheral nerve terminals. SP effects on cellular composition in the
      cutaneous response to injury remain unclear. Based on our previous observations
      about SP effects on wound repair, we hypothesized that topical SP increases
      inflammatory cell density infiltration early after injury. A full-thickness 1.5 x
      1.5 cm(2) wound was created on the dorsum of 8-9-week-old C57BL/6J-m+Lepr(db)
      mice (db/db). Wounds were treated daily with 300 muL of either normal saline
      (0.9% NaCl) or 10(-9) M SP for 7 days. Three wounds from each group were
      harvested at 2, 3, 7, 14, and 28 days. Samples underwent enzymatic digestion and
      were incubated with fluorescent-labeled antibodies. Using flow cytometry,
      cellular content and density for each sample was derived. Masson Trichrome
      stained histology specimens were prepared to confirm results. Cell density in the
      SP-treated wounds (11.3 x 10(7) cells/g tissue, standard deviation [SD]+/-1.5 x
      10(7)) was greater than in NaCl-treated wounds (7 x 10(7) cells/g tissue, SD+/
      2.3 x 10(7), p<0.05) at day 7 postwounding. SP significantly increased the
      density of leukocytes (2.1 x 10(7), SD +/-3.6 x 10(6) vs. 1.8 x 10(7), SD+/-4.9 x
      10(5), p<0.02) 3 days after wounding and the density of macrophages (2.9 x 10(7),
      SD+/-7.5 x 10(6) vs. 1.3 x 10(7), SD+/-1.4 x 10(6), p<0.05) 7 days after
      wounding. There were no significant differences in endothelial cell, leukocyte,
      or macrophage density at later time points. Topical SP treatment increases early
      inflammatory density in the healing wounds of db/db mice. These data support a
      role for nerve-mediated inflammation in cutaneous wound repair.

PMID- 18638273
TI  - Expression of genes encoding antimicrobial proteins and members of the toll-like
      receptor/nuclear factor-kappaB pathways in engineered human skin.
AB  - Skin functions as a first line of defense against microbial invasion. Tissue
      engineered cultured skin substitutes (CSS) are used to aid wound closure in
      massively burned patients, and have been used to facilitate safe and effective
      wound closure in adult patients with chronic wounds. Although they contain only
      two cell types at grafting, they can potentially contribute to innate defense
      against pathogens and stimulation of adaptive immunity. Gene microarrays were
      used to identify expression in cultured skin of genes involved in innate and
      adaptive immune responses, and to evaluate the effects of cytokine stimulation on
      expression levels. Cultured skin expressed multiple antimicrobial protein genes,
      including human beta defensins 1 and 2 and S100A12. In addition, the antiviral
      gene APOBEC3G, which was not previously identified in skin, was expressed in CSS
      and up-regulated by interleukin-1alpha and tumor necrosis factor alpha.
      Cathelicidin was not expressed in unstimulated CSS, but was induced by cytokine
      treatment. Further, genes encoding several proinflammatory cytokines and members
      of the toll-like receptor and nuclear factor kappa B pathways were expressed in
      CSS, suggesting that cells in CSS can mediate activation of inflammatory
      responses. The observed expression patterns indicate that engineered human skin
      utilizes innate defense mechanisms similar to those reported for native skin.
      Therefore, regulation of these pathways by cytokine stimulation may offer a
      mechanism for increasing innate immunity in CSS to combat wound infection after
      grafting onto patients.

PMID- 18638274
TI  - Epidermal growth factor protects fibroblasts from apoptosis via PI3 kinase and
      Rac signaling pathways.
AB  - The fibroplasia noted during wound repair is resolved by fibroblast cell death.
      How fibroblasts undergo death and how this is prevented by trophic growth factors
      present during the regenerative phase are unknown at the molecular level. We
      examined a model of staurosporine-induced apoptosis in fibroblasts. We
      demonstrated that epidermal growth factor (EGF) stimulation of fibroblast NR6WT
      expressing human EGF receptors blocks staurosporine-induced apoptosis by
      inhibiting the activation of caspase-3. The survival effect of EGF on rescuing
      apoptotic NR6WT involves signaling pathways that derive from PI3K and Rac; the
      blockade of apoptosis is abolished when PI3K and Rac signals are inhibited
      simultaneously. Furthermore, by using KP372-1, a specific Akt inhibitor, we found
      that downstream of Akt signaling pathways is absolutely required for the EGF
      rescue from staurosporine-induced apoptosis in NR6WT. Interestingly, EGF
      prevention of apoptosis induced by tumor necrosis factor-alpha in the face of
      cycloheximide blockade of protein translation occurs via a different set of
      pathways as the simultaneous inhibition of extracellular signal-regulated kinase,
      Rac, and PI3K signaling did not eliminate EGF from rescuing fibroblasts in the
      face of this cytokine. These findings indicate that EGF receptor activation
      provides survival response against staurosporine-induced apoptosis through signal
      pathways of PI3K and Rac, which then may prevent the activation of caspase-3.

PMID- 18638275
TI  - Development of an in vitro burn wound model.
AB  - Healing of a deeper burn wound is a complex process that often leads to scar
      formation. Skin wound model systems are important for the development of
      treatments preventing scarring. The aim of this study is to develop a
      standardized in vitro burn wound model that resembles the in vivo situation. A
      burn wound (10 x 2 mm) was made in ex vivo skin and the skin samples were
      cultured at the air-liquid interface for 7, 14, and 21 days. Cells in the skin
      biopsies maintained their viability during the 21-day culture period. During
      culture, reepithelialization of the wound took place from the surrounding tissue
      and fibroblasts migrated into the wound area. Cells of the epithelial tongue and
      fibroblasts near the wound margin were proliferating. During culture, skin
      derived antileukoproteinase and keratin 17 were expressed only in the epithelial
      tongue. Both collagen type IV and laminin were present underneath the newly
      formed epidermis, indicating that the basement membrane was restored. These
      results show that the burn wound model has many similarities to in vivo wound
      healing. This burn wound model may be useful to study different aspects of wound
      healing and testing pharmaceuticals and cosmetics on, e.g., migration and
      reepithelialization.

PMID- 18638277
TI  - Basic fibroblast growth factor (bFGF) alleviates the scar of the rabbit ear model
      in wound healing.
AB  - Studies suggest a possible antiscarring effect of basic fibroblast growth factor
      (bFGF) during wound healing. However, little is known about the precise
      pathological mechanisms of bFGF. In particular, there is only limited information
      available about the mechanism of exogenous administration of bFGF to scar
      formation. To investigate the effect of bFGF on the hypertrophic scar in the
      rabbit ear model and to clarify the mechanisms of bFGF on treatment for scar in
      wound healing, the rabbit ear model of wound healing was created and treated
      topically with bFGF once daily for 3 months; then we examined the changes of
      macroscopic and histopathological characteristics of scars and the expression of
      collagen and collagenase-1 (matrix metalloproteinase-1). The results of
      macroscopic and histologic characteristics revealed a significant difference
      between scars treated with bFGF and control scars. The expression of collagen in
      the scars treated with bFGF was decreased, as compared with the scars treated
      with saline. Further study revealed that bFGF could remarkably enhance expression
      of matrix metalloproteinase-1. bFGF could improve the quality of wound healing
      and remarkably alleviate the scar in the rabbit ear model in wound healing, which
      suggests that bFGF exerted a net negative effecton scar formation in wound
      healing. The evidence should contribute to a better understanding of the
      biological activities of bFGF during hypertrophic scar formation.

PMID- 18638276
TI  - The use of a semiocclusive dressing reduces epidermal inflammatory cytokine
      expression and mitigates dermal proliferation and inflammation in a rat
      incisional model.
AB  - Occlusive wound dressings are utilized clinically to accelerate wound healing and
      improve the final appearance of scars. In vivo and in vitro evidence suggests
      that one mechanism for this effect is maintenance of normal hydration in the
      epidermis, although the molecular signals remain uncharacterized. We sought to
      elucidate histological changes and some of the molecular signals involved in this
      effect in a rat model of wound semiocclusion. We utilized a rat linear incision
      model with surgical tape occlusion. Histological stains and quantitative real
      time PCR analysis were used to characterize the cellular and molecular effects of
      semiocclusion on the wound healing response. Semioccluded wounds demonstrated
      decreased epidermal thickness and cellularity and less mitotic epidermal activity
      when compared with nonoccluded control wounds. Associated dermal cellularity was
      similarly attenuated by semiocclusion. Finally, levels of proinflammatory
      cytokines interleukin-1-alpha and tumor necrosis factor-alpha were significantly
      decreased on postoperative day 3 at the transcriptional level when compared with
      nonoccluded wounds. Semiocclusive wound treatments significantly decrease
      epidermal thickness, cellularity, mitotic activity, and dermal cellularity as
      well as transcriptional levels of important epidermal mediators of inflammation
      in a rat incisional wound model.

PMID- 18638280
TI  - The drug treatment of status epilepticus in Europe: consensus document from a
      workshop at the first London Colloquium on Status Epilepticus.

PMID- 18638283
TI  - Transatlantic similarities and differences in the management of status
      epilepticus.

PMID- 18638284
TI  - Status epilepticus--an Australian perspective.

PMID- 18638285
TI  - Randomized controlled trials in status epilepticus.

PMID- 18638286
TI  - Termination of absence status epilepticus by low-dose intravenous levetiracetam.

PMID- 18638289
TI  - The pharmacogenomics of P-glycoprotein and its role in veterinary medicine.
AB  - Despite advancements in pharmacogenetics in human medicine, the incorporation of
      pharmacogenetics into veterinary medicine is still in its early stages of
      development. To date, efforts to understand the pharmacologic impact of genetic
      variation in veterinary species have largely focused on genes encoding for the
      membrane transporter, P-glycoprotein (P-gp). The emphasis on the role of P-gp is
      largely because of safety concerns associated with the use of some macrocyclic
      lactones in dogs. Because of the body of information available on this topic, we
      use P-gp as a platform for understanding the importance of population diversity
      in veterinary medicine. The impact of P-gp on drug pharmacokinetics and
      pharmacodynamics is considered, along with endogenous and exogenous factors that
      can modulate P-gp activity. The review includes discussion of how population
      diversity in P-gp activity can lead to susceptibility to certain diseases or
      alter patient response to environmental stress or pharmaceutical intervention. In
      addition, phenotypic diversity also needs to be considered, as demonstrated by
      the impact of P-gp up-regulation and drug resistance. The aim of this review was
      to set the stage for further exploration into the impact of genetic and
      phenotypic variability on drug pharmacokinetics, disease propensity, product
      formulation and drug response in both companion and food-producing animals.

PMID- 18638290
TI  - Impact of antimicrobial drug usage measures on the identification of heavy users,
      patterns of usage of the different antimicrobial classes and time-trends
      evolution.
AB  - Several measurement units are available to quantify antimicrobial usage in
      veterinary medicine, to obtain diverse measures such as the weight of active
      substance used, the live weight (LW) treated, the fraction of animals exposed,
      the number of treatments recorded or the cost represented. These measures can be
      applied to study practices variability between farms, to characterize patterns of
      usage of the different antimicrobial classes or to follow evolution of
      antimicrobial usage with time. An investigation was carried out to specifically
      explore the influence of measurement units on the conclusions obtained from such
      studies. Antimicrobial exposure was explored in a sample of turkey and chicken
      broiler flocks, using six different units [kg of active compound, treatments,
      days of administration, kg of LW treated, animal daily dose to treat 1 kg of LW
      (ADD(kg)) and euros] to compare flocks usage variability and patterns of use of
      the different antimicrobial classes. Time-trends evolutions of macrolides usage
      in turkey broilers, characterized by percentage of flocks exposed and LW treated,
      were also compared. In all analyses, the measure gave different results without
      equivalences, highlighting the necessity for care in choosing the measurement
      unit and caution in interpreting the figures obtained.

PMID- 18638291
TI  - Pharmacokinetics of valacyclovir in the adult horse.
AB  - Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed
      interest in the use of effective antiherpetic drugs in horses. The purpose of
      this study was to investigate the pharmacokinetics of valacyclovir (VCV), the
      prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized
      cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5
      g (7.7-11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7-34.1 mg/kg)
      VCV administered IG. Serum samples were obtained at predetermined times for
      acyclovir assay using high-performance liquid chromatography. Following the
      administration of 5 g VCV, the mean observed maximum serum ACV concentration
      (C(max)) was 1.45 +/- 0.38 (SD) microg/mL, at 0.74 +/- 0.43 h. At a dose of 15 g
      VCV, the mean C(max) was 5.26 +/- 2.82 microg/mL, at 1 +/- 0.27 h. The mean
      bioavailability of ACV from oral VCV was 60 +/- 12% after 5 g of VCV and 48 +/-
      12% after 15 g VCV, and did not differ significantly between dose rates (P >
      0.05). Superposition suggested that a loading dose of 27 mg/kg VCV every 8 h for
      2 days, followed by a maintenance dose of 18 mg/kg every 12 h, will maintain
      effective serum ACV concentrations.

PMID- 18638292
TI  - Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous
      dose of disodium fosfomycin in horses.
AB  - Pharmacokinetic parameters of fosfomycin were determined in horses after the
      administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously
      (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at
      time zero (C(S0)) was 112.21 +/- 1.27 microg/mL and 201.43 +/- 1.56 microg/mL for
      each dose level. Bioavailability after the SC administration was 84 and 86% for
      the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented
      minimum inhibitory concentration (MIC(90)) range of sensitive bacteria to
      fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 +/- 2.26
      microg/mL with 10 mg/kg SC and 72.14 +/- 3.04 microg/mL with 20 mg/kg SC) and
      that fosfomycin is considered a time-dependant antimicrobial, it can be concluded
      that clinically effective plasma concentrations might be obtained for up to 10 h
      administering 20 mg/kg SC. An additional predictor of efficacy for this latter
      dose and route, and considering a 12 h dosing interval, could be area under the
      curve AUC(0-12)/MIC(90) ratio which in this case was calculated as 996 for the 10
      mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If
      a more resistant strain is considered, the AUC(0-12)/MIC(90) ratio was calculated
      as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.

PMID- 18638293
TI  - Levamisole synergizes proliferation of intestinal IgA+ cells in weaned pigs
      immunized with vaccine candidate F4ac+ nonenterotoxigenic Escherichia coli
      strain.
AB  - Levamisole (2, 3, 5, 6-tetrahydro-6-phenylimidazole 2,1-b thiazole) is a well
      known nonspecific stimulator of host defence mechanisms. In previous
      investigations, we have found that levamisole acts on cell-mediated immunity in
      challenge-induced porcine postweaning colibacillosis (PWC). We assume that
      levamisole could also act synergistically on humoural immune response when
      applied as an adjuvant with vaccine candidate strains for oral immunization of
      weaned pigs against PWC. The influence of levamisole in combination with
      experimental F4ac(+) nonenterotoxigenic Escherichia coli (non-ETEC) vacinal
      strain on proliferation of IgA(+) cells was examined in 4-week-old weaned pigs
      experimentally infected with ETEC. We have performed identification and
      morphometric quantification of the plasma cell phenotype within jejunal/ileal
      mucosa. Plasma cells were identified by immunohistochemistry with monoclonal anti
      IgA antibodies and quantifying by use of digital image analysis. Quantification
      of IgA(+) cells from levamisole-primed vaccinated and challenge-infected weaned
      pigs showed significantly increased number (P < 0.05 for both jejunum and ileum)
      compared with those observed in unprimed vaccinated/challenge-infected controls.
      It is suggested from these results that levamisole may contribute in initiation
      of local humoural immune response to enteric pathogens, such as enterotoxigenic
      E. coli.

PMID- 18638294
TI  - Pharmacokinetics and physiological effects of intravenous hydromorphone in
      conscious dogs.
AB  - This study evaluated the pharmacokinetics, the sedative and anti-nociceptive
      effects of intravenous hydromorphone in dogs. Five adult dogs were administered
      hydromorphone (0.1 mg/kg and 0.2 mg/kg) and morphine (0.5 mg/kg and 1 mg/kg) at
      weekly intervals. Blood samples were drawn before and at 1, 2, 5, 15, 30, 60 and
      120 min after drug administration. Plasma hydromorphone only was measured by high
      pressure liquid chromatography (HPLC) with electrochemical detection and
      pharmacokinetic parameters calculated. Anti-nociceptive and sedation scores were
      submitted to Kruskal-Wallis one-way anova on ranks and post-hoc Bonferroni test
      with 5% significance level. The data fitted a two-compartment model with a fast
      distribution (<1 min for both doses) and slower elimination rate. Mean
      elimination half-life was 80 +/- 52.7 and 57.7 +/- 30.4 min for the high and low
      dose, respectively. The apparent mean volumes of distribution at steady-state
      were 7.2 +/- 3 and 4.5 +/- 2.4 L/kg, while the clearance was 74.7 +/- 19 and 68.1
      +/- 20 mL/kg/min for the high and low doses, respectively. Compared to saline,
      hydromorphone and morphine produced significant anti-nociception and sedation of
      similar magnitude for 120 min. In conclusion, intravenous hydromorphone has a
      large volume of distribution, and high clearance rate that exceeds hepatic blood
      flow. In dogs, it produced mechanical anti-nociception and sedation of a
      magnitude similar to morphine.

PMID- 18638295
TI  - Relative potency of ketamine and S(+)-ketamine in dogs.
AB  - The aim of this study was to determine the relative potency of racemic ketamine
      and S(+)-ketamine for the hypnotic effect and to evaluate the clinical anesthesia
      produced by equianesthetic doses of these two substances in dogs. One hundred and
      eight dogs were allocated in groups R2, R2.5, R3, R6, R9, R12, S2, S2.5, S3, S6,
      S9, and S12, to receive by intravenous route 2, 2.5, 3, 6, 9, and 12 mg/kg of
      ketamine or S(+)-ketamine, respectively. A dose-effect curve was drawn with the
      dose logarithm and the percentage of dogs that presented hypnosis in each group.
      The curve was used to obtain a linear regression, to determine the effective
      doses 100 and the potency relationship. In another experimental phase, eight
      groups of five dogs received 3, 6, 9 and 12 mg/kg of ketamine or S(+)-ketamine to
      evaluate the periods of latency, hypnosis, and total recovery. The times in which
      the dogs reached the sternal position, attempted to stand up for the first time,
      recovered the standing position, and started to walk were also recorded. The
      hypnotic dose for ketamine was 9.82 +/- 3.02 (6.86-16.5) mg/kg and for S(+)
      ketamine was 7.76 +/- 2.17 (5.86-11.5) mg/kg. The time of hypnosis was longer in
      R3 and the first attempt to stand up occurred early in R6 when compared with S3
      and S6 respectively. When R9 (100% of hypnosis with ketamine) and S6 [100% of
      hypnosis with S(+)-ketamine] were compared (1:1.5 ratio), the time to sternal
      position (12 +/- 2.5 and 20.2 +/- 5.6 min respectively) and the total recovery
      time (45 +/- 5.5 and 60.2 +/- 5.2 min respectively) were significantly shorter
      with S(+)-ketamine. It was concluded that the potency ratio between ketamine and
      S(+)-ketamine in dogs is smaller than the one reported in other species, and that
      the dose obtained after a reduction of 50%, as usually performed in humans, would
      not be enough to obtain equianesthetic effects in dogs.

PMID- 18638296
TI  - Pharmacokinetics and pharmacodynamics of ramipril and ramiprilat in healthy cats.
AB  - The pharmacokinetics of ramipril and its active metabolite, ramiprilat, was
      determined in cats following single and repeated oral doses of ramipril (Vasotop
      tablets) (once daily for 9 days) at dose rates of 0.125, 0.25, 0.5 and 1.0 mg/kg.
      The pharmacodynamic effects were assessed by measuring plasma angiotensin
      converting enzyme (ACE) activity. Maximum ramipril concentrations were attained
      within 30 min following a single dose and declined rapidly (concentrations were
      below the limit of quantification 4 h after treatment). Peak ramiprilat
      concentrations were detected at approximately 1.5 h. The apparent terminal half
      life (t((1/2)beta)) was > or =20 h irrespective of the dose. Ramiprilat
      accumulated in plasma (ratio of accumulation 1.3 to 1.9 depending on the dose
      rate) following repeated administration. Steady-state conditions were attained
      after the second dose. Excretion was predominant in faeces (87%) and to a lesser
      extent in urine (11%). The rate and extent of absorption of ramipril as well as
      its conversion to ramiprilat were not significantly influenced by the presence of
      food in the gastrointestinal tract. Plasma-ACE activity was almost completely
      abolished 0.5-2.0 h after treatment, irrespective of the dose rate. Significant
      inhibition of ACE activity of 54.7 to 82.6% (depending on the dosage) was still
      present 24 h after treatment. Treatment was well-tolerated in all cats. Ramipril
      at a dose rate of 0.125 mg/kg once daily produces significant and long-lasting
      inhibition of ACE activity in healthy cats. The appropriateness of this dosage
      regime needs to be confirmed in diseased cats.

PMID- 18638297
TI  - Pharmacokinetics of lidocaine following the application of 5% lidocaine patches
      to cats.
AB  - Lidocaine patches have been used to provide local analgesia in dogs and cats. We
      conducted this study to assess the systemic and local absorption of lidocaine
      from topical patches in cats. Eight 2-year-old cats received either intravenous
      lidocaine at 2 mg/kg or one 700 mg lidocaine patch placed on the lateral thorax
      for 72 h, in a cross-over randomized repeated measures design. Plasma was
      collected at specific times and the skin was biopsied at the time of patch
      removal for the quantitative analysis of lidocaine and its major metabolite,
      monoethylglycinexylidide (MEGX), by gas chromatography with mass spectrometry.
      Percent absorption time plots for systemic lidocaine appearance were constructed
      using the Loo-Riegelman method. Approximately, constant rate absorption was
      observed from 12-72 h after patch application at a mean +/- SD rate of 109 +/- 49
      microg/kg/h, resulting in steady-state lidocaine plasma concentrations of 0.083
      +/- 0.032 microg/mL and MEGX concentrations of 0.012 +/- 0.009 microg/mL. Overall
      bioavailability of transdermal lidocaine was 6.3 +/- 2.7%, and only 56 +/- 29% of
      the total lidocaine dose delivered by the patch reached systemic circulation.
      Skin lidocaine concentrations were much higher than plasma concentrations, at 211
      +/- 113 microg/g in the thoracic skin beneath the patch and 2.2 +/- 0.6 microg/g
      in the contralateral thoracic skin without the patch. As both lidocaine and MEGX
      were recovered from contralateral skin, it is likely that lidocaine accumulated
      in the skin from low systemic concentrations of circulating lidocaine over the 72
      h period of patch application. Plasma lidocaine concentrations remained well
      below systemically toxic concentrations, and no obvious clinical side effects
      were observed in any of the cats. The low systemic absorption rate coupled with
      high local lidocaine concentrations on the skin support the safe use of lidocaine
      patches in cats.

PMID- 18638298
TI  - Differences in hepatic cytochrome P450 activity correlate with the strain
      specific biotransformation of medetomidine in AX/JU and IIIVO/JU inbred rabbits.
AB  - Medetomidine is an alpha(2)-adrenoceptor agonist with sedative and analgesic
      properties. Previously we demonstrated significant differences in the response to
      medetomidine between two inbred rabbit strains, denoted IIIVO/JU and AX/JU. The
      aim of the present study was twofold: first, to compare the hepatic CYP450 enzyme
      activities between these rabbit strains [n = 13(male male,7 female
      female)/strain]. To this end, liver microsomes were incubated with known
      fluorescent substrates for the major drug-metabolizing CYP450 isoforms. A
      comparison of the obtained results indicated significant gender differences as
      well as differences between the two rabbit inbred strains. Secondly, the
      biotransformation rate of medetomidine in liver microsomes of both rabbit strains
      was determined using liquid chromatography coupled to tandem mass spectrometry.
      The rate of hydroxymedetomidine and medetomidine carboxylic acid formation was
      found to be significantly higher in the AX/JU strain. Specific CYP2D and CYP2E
      inhibitors could decrease the formation of both metabolites. Significant
      correlations were found between the rate of biotransformation of medetomidine and
      the activities of CYP2D and CYP2E, as well as between CYP450 enzyme activities
      and the anaesthetic response to medetomidine.

PMID- 18638299
TI  - Expression of MDR1, MRP2 and BCRP mRNA in tissues of turkeys.
AB  - MDR1, MRP2 and BCRP are members of the superfamily of ABC membrane transporters
      that export a large variety of structurally diverse substances out of the cell,
      hence being an integral part of various biological barriers. Here we report for
      the first time the tissue distribution of these ABC efflux transporters in the
      gastrointestinal tract (crop, proventriculus, duodenum, proximal and distal
      jejunum, ileum, caecum, colon) as well as in liver, kidney, lung, brain, adrenal
      gland, ovaries, oviduct and testes in BUT9 turkeys. MDR1 and BCRP mRNA expression
      was detected in all tissue samples, and the highest levels were measured in the
      small intestines. The tissue distribution of MRP2 mRNA was less consistent and
      some tissues seemed to lack any significant expression. Moreover, in
      consideration of previous findings suggesting that fluoroquinolones are
      substrates and modulators of ABC transporters, the effect of orally administered
      danofloxacin mesylate on the levels of MDR1, MRP2 and BCRP mRNA expression was
      investigated. Danofloxacin treatment resulted in a significant up-regulation of
      the measured transporters at the transcriptional level in the upper part of
      gastro-intestinal tract, liver and kidneys as well as in barrier-protected
      organs, such as the brain. However, despite this significant increase in the
      transcription levels, the pharmacokinetic parameters after repeated application
      of danofloxacin mesylate were not significantly altered.

PMID- 18638300
TI  - Commentary on Holmes et al. (2007): resolving the debate on when extinction risk
      is predictable.
AB  - We reconcile the findings of Holmes et al. (Ecology Letters, 10, 2007, 1182) that
      95% confidence intervals for quasi-extinction risk were narrow for many
      vertebrates of conservation concern, with previous theory predicting wide
      confidence intervals. We extend previous theory, concerning the precision of
      quasi-extinction estimates as a function of population dynamic parameters,
      prediction intervals and quasi-extinction thresholds, and provide an
      approximation that specifies the prediction interval and threshold combinations
      where quasi-extinction estimates are precise (vs. imprecise). This allows PVA
      practitioners to define the prediction interval and threshold regions of safety
      (low risk with high confidence), danger (high risk with high confidence), and
      uncertainty.

PMID- 18638301
TI  - The quest for a null model for macroecological patterns: geometry of species
      distributions at multiple spatial scales.
AB  - There have been several attempts to build a unified framework for macroecological
      patterns. However, these have mostly been based either on questionable
      assumptions or have had to be parameterized to obtain realistic predictions.
      Here, we propose a new model explicitly considering patterns of aggregated
      species distributions on multiple spatial scales, the property which lies behind
      all spatial macroecological patterns, using the idea we term 'generalized
      fractals'. Species' spatial distributions were modelled by a random hierarchical
      process in which the original 'habitat' patches were randomly replaced by sets of
      smaller patches nested within them, and the statistical properties of modelled
      species assemblages were compared with macroecological patterns in observed bird
      data. Without parameterization based on observed patterns, this simple model
      predicts realistic patterns of species abundance, distribution and diversity,
      including fractal-like spatial distributions, the frequency distribution of
      species occupancies/abundances and the species-area relationship. Although
      observed macroecological patterns may differ in some quantitative properties, our
      concept of random hierarchical aggregation can be considered as an appropriate
      null model of fundamental macroecological patterns which can potentially be
      modified to accommodate ecologically important variables.

PMID- 18638303
TI  - Thermodynamic considerations in solid adsorption of bound solutes for patient
      support in liver failure.
AB  - New detoxification modes of treatment for liver failure that use solid adsorbents
      to remove toxins bound to albumin in the patient bloodstream are entering
      clinical evaluations, frequently in head-to-head competition. While generally
      effective in reducing toxin concentration beyond that obtainable by conventional
      dialysis procedures, the solid adsorbent processes are largely the result of
      heuristic development. Understanding the principles and limitations inherent in
      competitive toxin binding, albumin versus solid adsorbent, will enhance the
      design process and, possibly, improve detoxification performance. An equilibrium
      thermodynamic analysis is presented for both the molecular adsorbent
      recirculating system (MARS) and fractionated plasma separation, adsorption, and
      dialysis system (Prometheus), two advanced systems with distinctly different
      operating modes but with similar equilibrium limitations. The Prometheus analysis
      also applies to two newer approaches: sorbent suspension reactor and microsphere
      based detoxification system. Primary results from the thermodynamic analysis are
      that: (i) the solute-albumin binding constant is of minor importance to
      equilibrium once it exceeds about 10(5) L/mol; (ii) the Prometheus approach
      requires larger solid adsorbent columns than calculated by adsorbent solute
      capacity alone; and (iii) the albumin-containing recycle stream in the MARS
      approach is a major reservoir of removed toxin. A survey of published results
      indicates that MARS is operating under mass transfer control dictated by solute
      albumin equilibrium in the recycle stream, and Prometheus is approaching
      equilibrium limits under current clinical protocols.

PMID- 18638304
TI  - Wound-healing gene family expression differences between fetal and foreskin cells
      used for bioengineered skin substitutes.
AB  - For tissue engineering, several cell types and tissues have been proposed as
      starting material. Allogenic skin products available for therapeutic usage are
      mostly developed with cell culture and with foreskin tissue of young individuals.
      Fetal skin cells offer a valuable solution for effective and safe tissue
      engineering for wounds due to their rapid growth and simple cell culture. By
      selecting families of genes that have been reported to be implicated in wound
      repair and particularly for scarless fetal wound healing including transforming
      growth factor-beta (TGF-beta) superfamily, extracellular matrix, and
      nerve/angiogenesis growth factors, we have analyzed differences in their
      expression between fetal skin and foreskin cells, and the same passages. Of the
      five TGF-beta superfamily genes analyzed by real-time reverse transcription
      polymerase chain reaction, three were found to be significantly different with
      sixfold up-regulated for TGF-beta2, and 3.8-fold for BMP-6 in fetal cells,
      whereas GDF-10 was 11.8-fold down-regulated. For nerve growth factors, midkine
      was 36-fold down-regulated in fetal cells, and pleiotrophin was 4.76-fold up
      regulated. We propose that fetal cells present technical and therapeutic
      advantages compared to foreskin cells for effective cell-based therapy for wound
      management, and overall differences in gene expression could contribute to the
      degree of efficiency seen in clinical use with these cells.

PMID- 18638305
TI  - Transplantation of meniscus regenerated by tissue engineering with a scaffold
      derived from a rat meniscus and mesenchymal stromal cells derived from rat bone
      marrow.
AB  - The purpose of this study was to assess transplantation of regenerated menisci
      using scaffolds from normal allogeneic menisci and bone-marrow-derived
      mesenchymal stromal cells (BM-MSCs) of rats. We reported that scaffolds derived
      from normal menisci seeded with BM-MSCs in vitro could form meniscal tissues
      within 4 weeks. Then, we hypothesized that our tissues could be more beneficial
      than allogeneic menisci regarding early maturation and chondroprotective effect.
      Bone marrow was aspirated from enhanced green fluorescent protein transgenic
      rats. BM-MSCs were isolated and seeded onto scaffolds which were prepared from
      Sprague-Dawley rat menisci. After 4 weeks in coculture, the tissues were
      transplanted to the defect of menisci. Repopulation of BM-MSCs and expression of
      extracellular matrices were observed in the transplanted tissues at 4 weeks after
      surgery. At 8 weeks, articular cartilage in the cell-free group was more damaged
      compared to that in the cell-seeded group or the meniscectomy group.

PMID- 18638306
TI  - A coronary active perfusion system for off-pump coronary artery bypass grafting
      in an experimental porcine model: the relationship between flow rate and
      myocardial function.
AB  - We developed a coronary active perfusion system (synchronized arterial flow
      ensuring system [SAFE-System]) to prevent myocardial ischemia during distal
      anastomosis in off-pump coronary artery bypass grafting (CABG). The purpose of
      this study was to identify the relationship between the flow rate of the SAFE
      System and myocardial function. Studies were performed on pigs, which were
      divided into five groups: external shunt perfusion group (group A, n = 6); 0.1
      mL/beat flow rate for the SAFE-System group (group B, n = 6); 0.2 mL/beat flow
      rate group (group C, n = 6); 0.3 mL/beat flow rate group (group D, n = 6); and
      0.4 mL/beat flow rate group (group E, n = 6). Regional myocardial blood flow and
      left ventricular function were monitored for 30 min. The regional myocardial
      blood flow in group A was severely decreased (P < 0.001), and was significantly
      lower than in the other groups (P < 0.001). The slope of the end-systolic
      pressure-volume relationship, and the slope of the preload recruitable stroke
      work relationship in groups A, D, and E were lower than in groups B and C. As
      compared with the use of a passive external shunt, a coronary active perfusion
      system provides adequate myocardial blood flow and hemodynamics. It was possible
      to maintain left ventricular function when using 0.1 or 0.2 mL/beat flow rate.
      The use of a coronary active perfusion system appears to make the off-pump CABG
      procedure safer and may increase the application of off-pump bypass grafting.

PMID- 18638307
TI  - A magnetically levitated centrifugal blood pump with a simple-structured
      disposable pump head.
AB  - A magnetically levitated centrifugal blood pump (MedTech Dispo) has been
      developed for use in a disposable extracorporeal system. The design of the pump
      is intended to eliminate mechanical contact with the impeller, to facilitate a
      simple disposable mechanism, and to reduce the blood-heating effects that are
      caused by motors and magnetic bearings. The bearing rotor attached to the
      impeller is suspended by a two degrees-of-freedom controlled radial magnetic
      bearing stator, which is situated outside the rotor. In the space inside the
      ringlike rotor, a magnetic coupling disk is placed to rotate the rotor and to
      ensure that the pump head is thermally isolated from the motor. In this system,
      the rotor can exhibit high passive stiffness due to the novel design of the
      closed magnetic circuits. The disposable pump head, which has a priming volume of
      23 mL, consists of top and bottom housings, an impeller, and a rotor with a
      diameter of 50 mm. The pump can provide a head pressure of more than 300 mm Hg
      against a flow of 5 L/min. The normalized index of hemolysis of the MedTech Dispo
      is 0.0025 +/- 0.0005 g/100 L at 5 L/min against 250 mm Hg. This is one-seventh of
      the equivalent figure for a Bio Pump BPX-80 (Medtronic, Inc., Minneapolis, MN,
      USA), which has a value of 0.0170 +/- 0.0096 g/100 L. These results show that the
      MedTech Dispo offers high pumping performance and low blood trauma.

PMID- 18638308
TI  - Comparison of a pulsatile blood pump and a peristaltic roller pump during
      hemoperfusion treatment in a canine model of paraquat poisoning.
AB  - This study examined the treatment efficacy and the damage to the blood during
      hemoperfusion for treating paraquat poisoning using two blood pump mechanisms.
      Paraquat-poisoned animal models were prepared. A conventional hemodialysis
      machine, AK90, with a peristaltic roller pump and a cardiopulmonary support
      system, T-PLS, with a pulsatile blood pump were used during the animal
      experiments. A total of 12 dogs were treated with hemoperfusion using a charcoal
      column. Six dogs were treated with hemoperfusion and T-PLS, and the other six
      were treated with AK90. A paraquat dose of 30 mg/kg was administrated by an
      intravenous injection. Both pumps maintained blood flow rates of 125 mL/min
      measured by an ultrasonic flowmeter. For anticoagulation, heparin was
      administrated by an initial bolus (250 IU/kg) and a continuous injection (100
      IU/kg/h). During the experiments, T-PLS and AK90 showed a similar toxin removal
      efficacy. Both devices decreased the plasma paraquat concentration to 10% of the
      initial dose within 4-h hemoperfusion. The two pumps showed similar hemolysis
      properties with acceptable levels. Although T-PLS was developed as a
      cardiopulmonary bypass system, it can also be used as a hemoperfusion treatment
      device.

PMID- 18638309
TI  - A new synthetic dialyzer with advanced permselectivity for enhanced low-molecular
      weight protein removal.
AB  - Optimizing solute removal at minimized albumin loss is a major goal of dialyzer
      engineering. In a prospective, randomized, crossover study on eight patients (age
      63 +/- 14 years) on maintenance hemodialysis, the new Baxter Xenium 170 high-flux
      dialyzer (BX), which contains a 1.7-m(2) PUREMA H dialysis membrane, was compared
      with two widely used reference high-flux dialyzers currently available for
      hemodialysis in North America, the Fresenius Optiflux 180 NR (FO) and the Gambro
      Polyflux 170 H (GP). Solute removal and biocompatibility were assessed in
      hemodialysis for 240 min at blood and dialysate flow rates of 300 and 500 mL/min,
      respectively. Additional ex vivo experiments detecting the interleukin-1beta (IL
      1b) generation in recirculated donor blood were performed to demonstrate the
      pyrogen retention properties of the dialyzers. The instantaneous plasma
      clearances were similar for the three dialyzers except for cystatin c (cysc), for
      which a lower clearance was measured with FO as compared with BX and GP after 30
      and 180 min of hemodialysis. The reduction ratios (RRs) corrected for the
      hemoconcentration of beta(2)-microglobulin and cysc were lower in FO (44 +/- 9
      and 35 +/- 9%, respectively) versus BX (62 +/- 6 and 59 +/- 7%, respectively) and
      GP (61 +/- 7 and 56 +/- 8%, respectively). The RRs of the cytokine tumor necrosis
      factor alpha and interleukin-6 were not different between the dialyzers. The
      albumin loss was <300 mg for all filters. No differences between the dialyzers
      were found in the biocompatibility parameters showing very low leukocyte and
      complement activation. The ex vivo recirculation experiments revealed a
      significantly higher IL-1b generation for GP (710 +/- 585 pg/mL) versus BX (317
      +/- 211 pg/mL) and FO (151 +/- 38 pg/mL). BX is characterized by a steep solute
      sieving profile with high low-molecular weight protein removal at virtually no
      albumin loss and an excellent biocompatibility. This improved performance may be
      regarded as a contribution to optimal dialysis therapy.

PMID- 18638310
TI  - Sensitivity of the primary stability of a cementless hip stem to its position and
      orientation.
AB  - Using computed tomography (CT)-based preoperative planning software, we can
      define with good accuracy the position of a cementless hip stem inside the host
      bone, but previous studies suggest that the pose the surgeon achieves during
      freehand surgery may differ from the planned one even by some millimeters.
      Advances in simulation now make it possible to predict the primary stability of
      the stem in a given position during the preoperative planning, but is the
      stability predicted for the planned pose indicative of that we can expect for the
      achieved pose? The aim of the present study was to verify how this prediction is
      affected by the differences observed between the planned and the achieved poses.
      Two finite element models of an implanted femur were generated, one with the stem
      in the planned pose, and one with the stem in the achieved pose, as defined from
      postoperative CT scans. When compared to experimental measurements, the model
      with the achieved position was clearly more accurate (0.6 vs. 12% error over
      measured peak micromotion); however, the predictions of induced micromotions were
      different between the two models for less than 13%. It is thus concluded that
      while the implant position does have an effect on primary stability, the estimate
      of micromotion we can get from the planned position remains a clinically relevant
      indicator.

PMID- 18638311
TI  - Chondrogenesis from immortalized human mesenchymal stem cells: comparison between
      collagen gel and pellet culture methods.
AB  - Human mesenchymal stem cells (hMSCs) can differentiate into cells of connective
      tissue lineages, including cartilage. To overcome the limiting autogenous
      chondrocyte populations available in cartilage repair, various methods have been
      developed to maximize chondrogenesis of hMSCs in vitro, most of which use cells
      derived from primary culture. In this study, we compared chondrogenesis of
      immortalized hMSCs embedded in collagen gel to those grown in pellet culture. The
      hMSCs in collagen scaffolds expressed more glycosaminoglycan than those in pellet
      culture. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis demonstrated that the expression of genes encoding sox-9, aggrecan, and
      types I and II collagen increased in pellet culture over time. However, in the
      collagen cultures, only type II collagen and aggrecan expression increased over
      time, whereas sox-9 expression remained unchanged and type I collagen expression
      decreased. These results indicate that the immortalized hMSC line is a promising
      tool for further in vitro chondrogenic studies.

PMID- 18638312
TI  - Laboratory performance testing of venous cannulae during inlet obstruction.
AB  - Venous cannulae undergo continuous improvements to achieve better and safer
      venous drainage. Several cannula tests have been reported, though cannula
      performance during inlet obstruction has never been a test criterion. In this
      study, five different cannulae for proximal venous drainage were tested in a mock
      circulation that enabled measurement of hydraulic conductance after inlet
      obstruction by vessel collapse. Values for hydraulic conductance ranged from 1.11
      x 10(-2) L/min/mm Hg for a Thin-Flex Single Stage Venous Cannula with an open-end
      lighthouse tip to 1.55 x 10(-2) L/min/mm Hg for a DLP VAD Venous Cannula
      featuring a swirled tip profile, showing a difference that amounts to nearly 40%
      of the lowest conductance value. Excessive venous drainage results in potentially
      dangerous high-negative venous line pressures independent of cannula design.
      Cannulatip design featuring swirled and grooved tip structures increases drainage
      capacity and enhances cannula performance during inlet obstruction.

PMID- 18638313
TI  - Clitoral variation says nothing about female orgasm.

PMID- 18638314
TI  - Clitoral and penile size variability are not significantly different: lack of
      evidence for the byproduct theory of the female orgasm.

PMID- 18638315
TI  - Inappropriate comparisons and the weakness of cryptic choice: a reply to Vincent
      J. Lynch and D. J. Hosken.

PMID- 18638316
TI  - Combing evolution.

PMID- 18638317
TI  - An organizer controls the development of the "sword," a sexually selected trait
      in swordtail fish.
AB  - Male swordtail fish of the genus Xiphophorus (Poeciliidae) possess a "sword" that
      is composed of several colored elongated ventral fin rays of the caudal fin. The
      sword is a secondary sexual trait that evolved through sexual selection by female
      preference. To uncover the developmental mechanisms underlying the metamorphosis
      from a juvenile caudal fin to the sword, we have devised a transplantation
      protocol to assay the fate of single transplanted fin rays and their interactions
      with flanking rays. These experiments provide evidence for the existence of a
      previously unrecognized inductive signal that originates in those rays that
      develop into the two longest sword rays. This "sword organizer" causes adjacent
      fin rays to grow and become integrated into the sword and induces the development
      of an additional, typically pigmented sword in grafts to the dorsal part of the
      caudal fin. We show that the potential to develop a sword is restricted to
      certain parts of the caudal fin. Our findings suggest that the evolution of
      swords in swordtails required the acquisition of two developmental mechanisms:
      the establishment of signaling competence in prospective sword rays in the embryo
      or early larva, and its activation through androgen signaling in adult male fish.

PMID- 18638318
TI  - Bicoid occurrence and Bicoid-dependent hunchback regulation in lower
      cyclorrhaphan flies.
AB  - The homeobox gene bicoid functions as an anterior pattern organizer of the
      Drosophila embryo, but other than in higher flies (Cyclorrhapha), bicoid
      orthologues appear to be absent from insect genomes. In Drosophila, bicoid is
      expressed in an anterior-to-posterior protein gradient and regulates spatially
      restricted expression domains of segmentation genes in a concentration-dependent
      manner. hunchback, a direct transcriptional target of Bicoid, complements the
      "morphogen" activity of Bicoid. hunchback is activated by Bicoid throughout the
      anterior half of the blastoderm and a Bicoid-binding cis-regulatory element has
      been identified immediately upstream of the proximal hunchback promoter P2 of
      Drosophila and other higher Cyclorrhapha (Schizophora). bicoid and Bicoid
      dependent hunchback regulation are thought to have originated during or before
      the radiation of extant Cyclorrhapha, although the precise occurrence of these
      traits in lower Cyclorrhapha remains unknown. Previously, we have described a
      bicoid orthologue in Megaselia, a species of the lower cyclorrhaphan family
      Phoridae. Here, we report the occurrence of bicoid in two additional lower
      cyclorrhaphan families, Lonchopteridae and Platypezidae. We show that Megaselia
      Bicoid is required for anterior expression of Megaselia hunchback, and binds
      upstream of its P2 promoter. Furthermore, we report the expression of lacZ
      reporter constructs under the control of hunchback regulatory sequences from a
      range of lower cyclorrhaphan and non-cyclorrhaphan flies in transgenic Drosophila
      embryos. Our results are consistent with a cyclorrhaphan origin of bicoid and
      suggest that a Bicoid-binding enhancer upstream of the hunchback P2 promoter
      evolved at the latest in the last common ancestor of Megaselia and Schizophora.

PMID- 18638319
TI  - BAC transgenic analysis reveals enhancers sufficient for Hoxa13 and neighborhood
      gene expression in mouse embryonic distal limbs and genital bud.
AB  - We previously demonstrated that a approximately 1 Mb domain of genes upstream of
      and including Hoxa13 is co-expressed in the developing mouse limbs and genitalia.
      A highly conserved non-coding sequence, mmA13CNS, was shown to be insufficient in
      transgenic mice to direct precise Hoxa13-like expression in the limb buds or
      genital bud, although some LacZ expression from the transgene was reproducibly
      found in these tissues. In this report, we used beta-globin minimal promoter LacZ
      recombinant BAC transgenes encompassing mmA13CNS to identify a single critical
      region involved in mouse Hoxa13-like embryonic genital bud expression. By
      analyzing the expression patterns of these overlapping BAC clones in transgenic
      mice, we show that at least two sequences remote to the HoxA cluster are required
      collectively to drive Hoxa13-like expression in developing distal limbs. Given
      that the paralogous posterior HoxD and neighboring genes have been shown to be
      under the influence of long-range distal limb and genital bud enhancers, we
      hypothesize that both long-range enhancers have one ancestral origin, which
      diverged in both sequence and function after the HoxA/D cluster duplication.

PMID- 18638320
TI  - Expanded HOXA13 polyalanine tracts in a monotreme.
AB  - The N-terminal region of human HOXA13 has seven discrete polyalanine tracts. Our
      previous analysis of these tracts in multiple major vertebrate clades suggested
      that three are mammal-specific. We now report the N-terminal HOXA13 repetitive
      tract structures in the monotreme Tachyglossus aculeatus (echidna). Contrary to
      our expectations, echidna HOXA13 possesses a unique set of polyalanine tracts and
      an unprecedented polyglycine tract. The data support the conclusion that the
      emergence of expanded polyalanine tracts in proteins occurred very early in the
      stem lineage that gave rise to mammals, between 162 and 315 Ma.

PMID- 18638322
TI  - Digit reduction, body size, and paedomorphosis in salamanders.
AB  - The loss of digits is a widespread evolutionary trend in tetrapods which occurs
      in nearly every major clade. Alberch and Gale showed that the order in which
      digits are evolutionarily lost in salamanders versus frogs corresponds to the
      order in which they develop in each group, providing a classic example of
      developmental constraint. However, what actually drives the loss of digits in
      salamanders has remained unclear. Alberch and Gale suggested that loss of digits
      might be associated with paedomorphosis or with reduced body size. We test these
      hypotheses by combining morphometric and phylogenetic information for 98 species
      of salamanders. We find that digit loss is associated with both paedomorphosis
      and reduction in body size. However, these trends are surprisingly contradictory,
      in that paedomorphosis is significantly associated with an increase in body size
      in salamanders. Thus, much of the extreme digit reduction is found in the smaller
      species within paedomorphic clades that have, on average, unusually large body
      size. Our results show that the consequences of changes in body size on
      morphology are highly context dependent. We also show (possibly for the first
      time) a significant association between paedomorphosis and increased body size,
      rather than the expected association with reduced body size.

PMID- 18638321
TI  - Gene expression reveals unique skeletal patterning in the limb of the direct
      developing frog, Eleutherodactylus coqui.
AB  - The growing field of skeletal developmental biology provides new molecular
      markers for the cellular precursors of cartilage and bone. These markers enable
      resolution of early features of skeletal development that are otherwise
      undetectable through conventional staining techniques. This study investigates
      mRNA distributions of skeletal regulators runx2 and sox9 along with the cartilage
      dominant collagen 2(alpha)1 (col2a1) in embryonic limbs of the direct-developing
      anuran, Eleutherodactylus coqui. To date, distributions of these genes in the
      limb have only been examined in studies of the two primary amniote models, mouse
      and chicken. In E. coqui, expression of transcription factors runx2 and sox9
      precedes that of col2a1 by 0.5-1 developmental stage (approximately 12-24 h).
      Limb buds of E. coqui contain unique distal populations of both runx2- and sox9
      expressing cells, which appear before formation of the primary limb axis and do
      not express col2a1. The subsequent distribution of col2a1 reveals a primary limb
      axis similar to that described for Xenopus laevis. Precocious expression of both
      runx2 and sox9 in the distal limb bud represents a departure from the conserved
      pattern of proximodistal formation of the limb skeleton that is central to
      prevailing models of vertebrate limb morphogenesis. Additionally, runx2 is
      expressed in the early joint capsule perichondria of the autopod and in the
      perichondria of long bones well before periosteum formation. The respective
      distributions of sox9 and col2a1 do not reveal the joint perichondria but instead
      are expressed in the fibrocartilage that fills each presumptive joint capsule.
      These distinct patterns of runx2- and sox9-expressing cells reveal precursors of
      chondrocyte and osteoblast lineages well before the appearance of mature
      cartilage and bone.

PMID- 18638323
TI  - Low divergence in Dlx gene expression between dentitions of the medaka (Oryzias
      latipes) versus high level of expression shuffling in osteichtyans.
AB  - Serially homologous structures are believed to originate from the redeployment of
      a genetic cascade in different locations of the body. Serial homologs may diverge
      at the genetic and morphological level and acquire developmental independency
      (individualization). Teeth are repeated units that form dentitions found on
      different bones of the oral-pharyngeal cavity in gnathostomes and provide a good
      model to study such processes. Previous comparisons of dlx gene expression
      patterns between mouse oral teeth and zebrafish pharyngeal teeth showed a high
      level of divergence. Furthermore, these genes are differentially expressed in
      different teeth of the zebrafish, and in the mouse they are responsible for tooth
      identity (incisors vs. molars). We examined the potential divergence of dlx gene
      expression between oral and pharyngeal teeth by examining the expression pattern
      in the development of the first generation teeth of the medaka and comparing it
      with data from the zebrafish and the mouse. Out of the seven medaka dlx genes,
      five are expressed during odontogenesis compared with six in both the zebrafish
      and the mouse. The only difference observed between oral and pharyngeal teeth in
      the medaka is an earlier expression of dlx5a in the oral dental epithelium. The
      subset of dlx genes expressed in the medaka, zebrafish, and mouse is slightly
      different but their detailed expression patterns are highly divergent. Our
      results demonstrate a low constraint on dlx gene expression shuffling in the
      odontogenic cascade within osteichtyans but the non-individualization of oral and
      pharyngeal dentitions in the medaka.

PMID- 18638324
TI  - The taming of the shrew milk teeth.
AB  - A characteristic feature of mammalian dentition is the evolutionary reduction of
      tooth number and replacement. Because mice do not replace teeth, here we used
      Sorex araneus, the common shrew, as a model to investigate the loss of tooth
      replacement. Historically, shrews have been reported to initiate the development
      of several, milk or deciduous teeth but these soon become rudimentary and only
      the replacement teeth erupt. Shrews thus offer a living example of a derived
      mammalian pattern where the deciduous tooth development is being suppressed.
      Based on histological and gene expression analyses of serial sections, we suggest
      that S. araneus has discernible tooth replacement only in the premolar 4 (P4)
      position. Both generations of teeth express Shh in the enamel knot and in the
      inner enamel epithelium. Nevertheless, the deciduous P4 (dP4) is reduced in size
      during embryogenesis and is eventually lost without becoming functional. Analysis
      of growth shows that P4 replaces the dP4 in a "double-wedge" pattern indicative
      of competitive replacement where the suppression of the deciduous tooth coincides
      with the initiation of its replacement. Because activator-inhibitor mechanisms
      have been implicated in adjacent mouse molars and in transgenic mice with
      continuous tooth budding, we suggest that evolutionary suppression of deciduous
      teeth may involve early activation of replacement teeth, which in turn begin to
      suppress their deciduous predecessors.

PMID- 18638325
TI  - Temperature-dependent plasticity of segment number in an arthropod species: the
      centipede Strigamia maritima.
AB  - The evolution of arthropod segment number provides us with a paradox, because,
      whereas there is more than 20-fold variation in this character overall, most
      classes and orders of arthropods are composed of species that lack any variation
      in the number of segments. So, what is the origin of the higher-level variation?
      The centipede order Geophilomorpha is unusual because, with the exception of one
      of its families, all species exhibit intraspecific variation in segment number.
      Hence it provides an opportunity to investigate how segment number may change in
      a microevolutionary context. Here, we show that segment number can be directly
      altered by an environmental factor (temperature)-this is the first such
      demonstration for any arthropod. The direction of the effect is such that higher
      temperature during embryogenesis produces more segments. This potentially
      explains an intraspecific cline in the species concerned, Strigamia maritima, but
      it does not explain how such a cline is translated into the parallel
      interspecific pattern of lower-latitude species having more segments. Given the
      plastic nature of the intraspecific variation, its link with interspecific
      differences may lie in selection acting on developmental reaction norms.

PMID- 18638329
TI  - End of life decision-making in paediatrics.

PMID- 18638326
TI  - Deuterostomes in a twist: the origins of a radical new body plan.
AB  - Echinoderms have a unique ontogeny and adult structure, and, among Bilateria, are
      the phylum that has diverged most radically in appearance from the ancestral body
      plan. Embryology and gene expression studies suggest how this transformation may
      have occurred while paleontological data provide direct evidence for the order in
      which these events took place. Comparing echinoderm ontogeny and genetic
      developmental signalling patterns with those of their sister group, the
      hemichordates, suggests that an evolutionary switch from posterior facultative to
      anterior obligate larval attachment proved the critical trigger. This
      necessitated introduction of a phase of torsion in development to bring the mouth
      into a more appropriate orientation for filter feeding, which in turn rotated the
      axis of the developing adult 90 degrees out of alignment with Hox and other body
      patterning genes. As a result the developing echinoderm rudiment came to receive
      a complex mosaic of anterior-posterior signalling, and extensive co-option of
      signalling pathways was able to take place. The fossil record shows that early
      (pre-radiate) echinoderms were much more hemichordate-like, with a muscular post
      anal stalk and facultative attachment, and probably developed maintaining
      continuity with larval axes, as in hemichordates, although left-right asymmetry
      was more highly developed. Anterior attachment and torsion, however, were clearly
      part of the developmental pattern of helicoplacoids and (to a much greater
      extent) in subsequent pentaradiate forms.

PMID- 18638330
TI  - Discussing withdrawing and withholding of life-sustaining medical treatment in a
      tertiary paediatric hospital: a survey of clinician attitudes and practices.
AB  - AIM: To better understand current attitudes and practices relating to discussions
      concerning the withholding and withdrawing of life-sustaining medical treatment
      (WWLSMT) among medical staff in the paediatric setting. METHODS: An anonymous
      online survey of paediatricians (senior medical staff - SMS) and paediatric
      trainees (junior medical staff - JMS) likely to be involved in the care of
      children with life limiting illness. RESULTS: A total of 162 responses were
      obtained (response rate 42%). SMS indicated feeling more comfortable with their
      abilities to discuss WWLSMT than JMS. Barriers to discussing WWLSMT were numerous
      and included clinician concerns about family readiness for the discussion,
      prognostic uncertainty, family disagreement with the treating team regarding the
      child's prognosis/diagnosis and concerns about how to manage family requests for
      treatments that are not perceived to be in the child's best interests. Fifty
      eight per cent of JMS and 35.8% of SMS reported receiving no specific
      communication training regarding WWLSMT. Most learned through experience and by
      observing more senior colleagues. There was a high level of support for
      additional training in this area and for the provision of resources such as
      discussion guidelines and a structured form for documenting the outcomes WWLSMT
      discussions. CONCLUSION: The majority of JMS feel less comfortable with their
      abilities to facilitate these discussions than their senior colleagues. The
      results of this study suggest that although confidence correlates with
      experience, junior and senior clinicians are eager to improve their skills
      through ongoing professional development and the provision of resources. The
      education needs of JMS and SMS appear to be different.

PMID- 18638331
TI  - Discussing withholding and withdrawing of life-sustaining medical treatment in
      paediatric inpatients: audit of current practice.
AB  - AIM: To understand the circumstances of inpatient deaths at a tertiary paediatric
      hospital and current practices regarding the timing and documentation of
      discussions concerning the withholding and withdrawing of life-sustaining medical
      treatment (WWLSMT). METHODS: Retrospective review of the medical records of 50
      consecutive inpatient deaths. RESULTS: In total, 84% of inpatient deaths occurred
      in an intensive care setting. In all, 74% of patients had an underlying life
      limiting or life-threatening condition and death was documented as having been
      expected in the short term in 88% of patients. Life-sustaining treatment was
      either withdrawn or limited prior to death in 84% of cases. There was documented
      family involvement in the decision-making process in 98% of cases. A total of 83%
      of discussions first took place on the day of death itself or in the week leading
      up to the child's death. Although medical staff frequently documented the outcome
      of these discussions, the content, clarity and accessibility of documentation
      varied widely. CONCLUSIONS: The majority of inpatient deaths at The Royal
      Children's Hospital occur in acute circumstances and involve patients with
      chronic conditions. In most cases, death follows WWLSMT. Discussions with
      families are documented as first occurring relatively late in the course of the
      final admission although opportunities for earlier discussions may exist. Further
      research is needed to understand more about how and when discussions actually
      take place, what the barriers to communication are and to what extent
      opportunities exist for discussions to be initiated earlier in the illness
      course.

PMID- 18638332
TI  - Withdrawal and limitation of life-sustaining treatments in a paediatric intensive
      care unit and review of the literature.
AB  - OBJECTIVES: To examine withdrawal and limitation of life-sustaining treatment
      (WLST) in an Australian paediatric intensive care unit (PICU) and to compare this
      experience with published data from other countries. DESIGN: Retrospective chart
      review and literature review. SOURCE OF DATA: Review of 12 months of patient
      records from a tertiary Australian children's teaching hospital. Medline search
      using relevant key words focusing on death and PICU. RESULTS: Twenty of 27 deaths
      (74%) followed either WLST (n = 16) or Do Not Resuscitate (DNR) orders (n = 4);
      five children failed cardiopulmonary resuscitation (CPR); and two children were
      brain-dead. Meetings between the medical team and family were documented for 15
      of 16 children (93.8%) before treatment was withdrawn. The average time between
      withdrawal of life support and death was 13 min. A review of the English-language
      literature revealed that 18-65% occurring in PICUs worldwide follow WLST and/or
      institution of DNR orders. Rates were higher (30-65%) in North America and Europe
      than elsewhere. Most PICU deaths occurred within 3 days of admission. North
      American and British parents appear to be involved in decisions regarding
      withdrawal and limitation of treatment more often than parents in other
      countries. CONCLUSIONS: Withdrawal and limitation of life-sustaining treatment
      was more common in an Australian children's hospital ICU than has been reported
      from other countries. Details of discussion with parents, including the basis for
      any decision to WLST, were almost always documented in the patient's medical
      record.

PMID- 18638333
TI  - Juvenile onset globoid cell leukodystrophy masquerading as XL
      adrenoleukodystrophy.
AB  - Krabbe's disease, or globoid cell leukodystrophy (GLD), is an autosomal recessive
      condition where the commonest presentation is the rapid neurological
      deterioration typical of the early onset subtype. Later onset subtypes, with more
      protean presentations and outcomes, also exist. These must be distinguished from
      other types of leukodystrophies, such as Adrenoleukodystrophy, as the prognosis
      is extremely variable. We describe a patient with late onset GLD (LOGLD) with
      imaging findings consistent with a diagnosis of Adrenoleukodystrophy. The
      importance of interpreting imaging findings in conjunction with the clinical and
      biochemical information is highlighted.

PMID- 18638334
TI  - Tendon sheath abscess and severe carbamazepine hypersensitivity.
AB  - We report a 10-year-old girl with enthesitis and Staphylococcus aureus tendon
      sheath abscess as complications of severe carbamazepine hypersensitivity. Our
      patient had an adverse reaction to intravenous immunoglobulin and this, as well
      as the use of corticosteroids, may have contributed to her condition.

PMID- 18638335
TI  - Pulseless electrical activity after rapid administration of fresh frozen plasma.
AB  - We present two extreme low birthweight preterm neonates who developed pulseless
      electrical activity during dilutional exchange transfusions with fresh frozen
      plasma (FFP). Both were polycythaemic recipient twins delivered prematurely
      because of foetal compromise as a result of twin-to-twin transfusion syndrome.
      The two events were associated with an acute fall in ionised calcium. We discuss
      the mechanism of these cardiac arrests and highlight the care required when
      infusing citrate containing blood products, particularly FFP, in order to avoid
      causing acute life-threatening hypocalcaemia.

PMID- 18638337
TI  - Re: Naloxone use in neonatal resuscitation.

PMID- 18638338
TI  - Re: Botulinum neurotoxin A: an unusual systemic effect 43 (2007) 499-501.

PMID- 18638339
TI  - The involuted facial haemangioma: a hidden space and potential problem.

PMID- 18638341
TI  - A 10-day-old neonate with fulminant hepatitis.

PMID- 18638342
TI  - Beta-thalassemia major and Down's syndrome.

PMID- 18638343
TI  - Regulation of cellulose synthesis--another player in the game?

PMID- 18638344
TI  - Plant-microbe and plant-insect interactions meet common grounds. International
      Conference on Biotic Plant Interactions, Brisbane, Australia, March 2008.

PMID- 18638345
TI  - Corneal stromal sequestration in a dog.
AB  - A case of corneal sequestrum in a 9-year-old Shih Tzu is reported. On the
      ophthalmic examination a brown-pigmented ulcer with mild edema and corneal
      vascularization was present. The brownish plaque was facing an inferior palpebral
      tumor. A superficial keratectomy followed by a grid keratotomy and removal of the
      palpebral mass were performed. Histological findings revealed an inflammatory
      cell infiltration underneath the acellular stromal layers. No melanin granules
      were observed. No vascular infiltration was present within the necrotic stroma.
      The surgical area healed and no recurrence has been reported by the owners at the
      time of writing. To the authors' knowledge, this is the first report of a corneal
      sequestrum in a dog.

PMID- 18638346
TI  - A retrospective study on the prevalence of primary cataracts in two pedigrees
      from the German population of English Cocker Spaniels.
AB  - OBJECTIVE: Two pedigrees from the German English Cocker Spaniel population are
      presented to illustrate the familial occurrence of primary cataract (CAT) in
      single- and multicolored English Cocker Spaniels. The aim was to characterize
      similarities and differences in the prevalence and formation of CAT in these
      separately bred color variants of English Cocker Spaniels. MATERIALS: The study
      was based on the veterinary records for presumed inherited eye diseases of 1232
      English Cocker Spaniels which were provided by the German panel of the European
      Eye Scheme for diagnosis of inherited eye diseases in animals (DOK,
      <http://www.dok-vet.de>). Data included information on 615 single-colored and 617
      multicolored English Cocker Spaniels. RESULTS: CAT was diagnosed in 92 (14.96%)
      of the single-colored and 34 (5.51%) of the multicolored English Cocker Spaniels.
      The pedigree of the single-colored English Cocker Spaniels included 40
      ophthalmologically examined dogs with 18 unaffected and 22 affected dogs. The
      pedigree of the multicolored English Cocker Spaniels contained 16
      ophthalmologically examined dogs with 11 unaffected and five affected dogs.
      CONCLUSIONS: In both color variants of the English Cocker Spaniels different
      forms of primary CAT with respect to location within the lens occurred among
      close relatives. Appearance of CAT was very heterogeneous without obvious sex
      differences. The sample pedigrees do not support the assumption of familial
      segregation of specific forms of primary CAT in English Cocker Spaniels.

PMID- 18638347
TI  - Microstructure and glycosaminoglycan ratio of canine cornea after reconstructive
      transplantation with glycerin-preserved porcine amniotic membranes.
AB  - OBJECTIVE: Although amniotic membranes of canine, feline, and equine species have
      some advantages as corneal transplantation material in many canine ocular
      diseases, their softness, thinness, and low availability can pose problems. As an
      alternative, the more abundant porcine amniotic membranes may be used. This paper
      describes the use of glycerin-preserved porcine amniotic membranes in corneal
      transplantation in eight normal dogs. METHOD: A 0.4-mm deep recipient bed in the
      axial cornea of the OS of all dogs was created using an 8-mm Barron radial vacuum
      trephine. The recipient bed was then filled with amnion, and the entire cornea
      was covered with another piece of the glycerin-preserved membrane. The ocular
      signs evaluated were corneal opacity and corneal vascularization. The dogs were
      euthanized on days 5, 10, 20, or 40 after surgery, and samples were collected to
      evaluate corneal thickness, parenchymal cell number, mean collagen fibril
      diameter, collagen fibril content and the glycosaminoglycan (GAG) ratio. RESULTS:
      Corneal opacity was observed immediately after surgery. Restoration of corneal
      transparency, regression of corneal vascularization, and visualization of the
      pupil and iris were noted on day 40. CONCLUSIONS: The clinical observations were
      supported histologically by regained corneal thickness, parenchymal cell number,
      mean collagen fibril diameter, collagen fibril content, and GAG ratio, suggesting
      that this technique may be a novel method for the treatment of ocular surface
      disorders.

PMID- 18638348
TI  - Intranictitans tacking for replacement of prolapsed gland of the third eyelid in
      dogs.
AB  - OBJECTIVE: To evaluate a new procedure for fixation of prolapsed nictitans glands
      to the cartilage of the nictitans that will not interfere with the mobility of
      the nictitating membrane. METHODS: A prospective clinical trial utilizing a
      nonabsorbable suture to anchor the prolapsed gland to the cartilage of the third
      eyelid was undertaken. Fifteen eyes of 10 dogs were included in the study. A 4-0
      nylon suture was passed from the anterior surface of the third eyelid through the
      base of the cartilage to the posterior aspect and then tunneled circumferentially
      beneath the conjunctiva over and around the prolapsed gland. The suture was then
      passed through the cartilage again to the anterior face of the third eyelid. The
      gland was replaced into its normal position as the suture was slowly tightened
      and then tied on the anterior aspect of the nictitans. RESULTS: Over a period of
      several weeks, the glands reduced in size and took on a normal appearance. All
      glands but one remained in place for the length of follow-up, which ranged from 2
      weeks to 33 months. CONCLUSIONS: This procedure results in acceptable cosmetic
      effects with the return of the gland to its normal position posterior to the
      nictitating membrane. The advantage of this technique over traditional tacking to
      the orbital rim is that the third eyelid retains its normal mobility and, thus,
      its protective functions. The procedure once mastered is very quick and can be
      performed in less time than many of the traditional replacement techniques.

PMID- 18638349
TI  - Myocilin protein levels in the aqueous humor of the glaucomas in selected canine
      breeds.
AB  - OBJECTIVE: To compare aqueous humor myocilin protein levels in dogs with the
      primary glaucomas to those with the secondary glaucomas, primary cataracts, and
      diabetic cataracts. MATERIALS AND METHODS: Four groups were selected, based on
      diagnosis by the attending veterinary ophthalmologists and included: primary
      glaucoma (primary open-angle glaucoma (POAG) and primary closed angle glaucoma
      (PCAG); n = 155); secondary glaucoma (n = 94); primary (presumed inherited)
      cataract (n = 142), and diabetic cataract (n = 83). A total of 474 samples (187
      males, 263 females, 24 unreported) with average ages of 117 months for the males
      and 101 months for the females were analyzed. Myocilin protein was measured using
      the Coomassie staining and Western blot methods relative to a myocilin control.
      RESULTS: Differences were seen between nonglaucomatous (cataractous) and
      glaucomatous dogs with myocilin levels in glaucomatous eyes being many times
      higher than those in the cataractous dogs. Primary glaucomatous dogs were found
      to have an aqueous humor myocilin protein level of 17.30 +/- 1.03 units.
      Secondary glaucomas had the highest level of myocilin in the aqueous humor with
      19.27 +/- 1.41 units. Diabetic cataractous dogs had the lowest levels of myocilin
      reported with 6.60 +/- 0.88 (mean +/- SEM) units. Normal (cataractous) dogs had a
      myocilin level in the aqueous humor of 8.05 +/- 0.86 units. CONCLUSION: Aqueous
      humor protein levels were elevated, relative to the myocilin control, in both the
      primary and secondary glaucoma groups compared to the cataract and diabetic
      cataract groups. Like in the Beagle POAG, aqueous humor myocilin protein levels
      are increased. Further studies are indicated to investigate the exact role of the
      aqueous humor myocilin protein in the genesis in increased IOP in these primary
      glaucomatous breeds.

PMID- 18638350
TI  - Retinopathy of Coton de Tulear dogs: clinical manifestations,
      electroretinographic, ultrasonographic, fluorescein and indocyanine green
      angiographic, and optical coherence tomographic findings.
AB  - OBJECTIVES: To document the clinical manifestations, development, progression,
      and mode of inheritance of the retinopathy of Coton de Tulear dogs. MATERIALS AND
      METHODS: Multiple Coton de Tulear dogs were examined with biomicroscopy, indirect
      ophthalmoscopy, photopic and scotopic electroretinography, fluorescein and
      indocyanine green angiography, optical coherence tomography, ultrasonography, and
      fundic photography for 3 years. RESULTS: The retinopathy of Coton de Tulear dogs
      is inherited as an autosomal recessive condition and manifests as multifocal
      serous retinal detachments in homozygous puppies, between 3 and 4 months of age.
      Optic coherence tomography and ultrasonography confirm multiple focal serous
      retinal detachments. Serial fundic photographs confirmed minimal progression of
      lesions beyond 1 year of age. Electroretinography identified diminished scotopic
      and photopic amplitudes; however, the only significant differences between
      affected and age-matched control Coton de Tulear dogs were noted during photopic
      flicker electroretinograms. Leakage of fluorescein or indocyanine green through
      the blood ocular barriers was not detected during repeated angiograms prior to,
      during, and after development of the retinopathy. There was no focal pooling of
      fluorescein in any of the dogs examined. Focal retinal thinning was detected with
      optical coherence tomography over each detachment and the serous content of some
      of the bullae diminish after several years leaving focal areas of hyper
      reflectivity. CONCLUSIONS: Multifocal retinopathy of Coton de Tulear dogs is
      inherited as an autosomal recessive condition. The retinopathy manifests early in
      life as nonprogressive multifocal bullous retinal detachments. The blood ocular
      barrier remains intact. Photopic and scotopic electroretinography are minimally
      diminished compared to age-matched dogs.

PMID- 18638351
TI  - Use of a biosynthetic material to repair the surgical defect following excision
      of an epibulbar melanoma in a cat.
AB  - A limbal melanoma was surgically excised from the OS of a 4-year-old castrated
      male Domestic Short-haired cat (DSH). The resultant scleral defect was repaired
      by placement of A-cell bio-scaffold material. The patient responded well in the
      postoperative period with no apparent discomfort, nor any observable
      complications. No signs of recurrence have been evident nearly 2.5 years
      following surgical removal. A-cell appears to be a safe and reasonable option to
      lend support to corneoscleral defects following removal of neoplastic lesions. It
      carries with it the advantages of availability, minimal host rejection, and
      reduced potential for iatrogenic spread of infections agents.

PMID- 18638352
TI  - Use of ketamine, xylazine, and diazepam anesthesia with retrobulbar block for
      phacoemulsification in dogs.
AB  - OBJECTIVE: The study was undertaken to evaluate the use of ketamine, xylazine,
      and diazepam along with a local retrobulbar nerve block for routine
      phacoemulsification in the dog. Animals Ten clinically healthy mixed-breed dogs
      of either sex, weighing between 10 and 15 kg. PROCEDURES: Ten mixed-breed dogs
      were selected for unilateral cataract removal by phacoemulsification. Standard
      preoperative preparations for cataract surgery were followed. Pre-anesthetic
      medication consisted of atropine sulfate (0.02 mg/kg, SC). Anesthesia was induced
      by xylazine HCl (1.0 mg/kg, IM) followed by ketamine (5.0 mg/kg, IM). Anesthesia
      was maintained subsequently with IV ketamine and diazepam to effect and depth of
      anesthesia was assessed clinically by pedal reflex and jaw reflex. After
      induction of anesthesia, a retrobulbar nerve block was performed using 2 mL of 2%
      lignocaine. Eye position was graded after retrobulbar block and IOP was examined
      preoperative, post-anesthetic, 6 h postoperative and 24 h after surgery.
      Phacoemulsification was performed using the phaco-chop technique and an
      intraocular lens was placed. Anesthetic recovery and postoperative recovery
      following surgery was recorded. RESULT: The exposure of the globe in all the dogs
      was adequate; the desired central fixation of the eye was obtained and surgery
      could be performed uneventfully. The mean IOP recorded after induction of
      anesthesia was 15.75 +/- 0.82, which was not significantly (P > 0.01) different
      from pre-anesthetic values (14.85 +/- 0.85). CONCLUSION: Phacoemulsification was
      successfully performed with this anesthetic regimen without encountering major
      intraoperative or anesthetic complications.

PMID- 18638353
TI  - Ocular melanosis in the Cairn Terrier: histopathological description of the
      condition, and immunohistological and ultrastructural characterization of the
      characteristic pigment-laden cells.
AB  - OBJECTIVE: To describe the microscopic features and lineage of
      proliferating/infiltrating pigmented cells in ocular melanosis of Cairn Terriers.
      Animals studied Forty-nine globes removed from 45 Cairn Terriers with ocular
      melanosis and three globes from control dogs were available for microscopic
      examination. PROCEDURES: All globes were examined histologically, eight affected
      and three control globes were also examined by immunohistochemistry, and three
      affected and three control globes by transmission electron microscopy. RESULTS:
      Large round pigment-laden cells infiltrated the anterior uvea, obscured the
      drainage angle and were present within the sclera and episclera of affected
      globes. Similar pigmented cells were present in lower numbers in the posterior
      segment of the globe, the optic nerve meninges and periphery of the optic nerve.
      Changes due to chronic glaucoma were present in many globes and some had evidence
      of uveitis. Many of the pigmented cells were immunoreactive to HMB45 and some
      were MITF and vimentin positive. One globe, which was inflamed when removed, had
      many pigmented cells that were CD18 immunoreactive. The other eyes had lower
      numbers of CD18 positive cells. The pigmented cells were not immunoreactive to
      smooth muscle actin, S-100, MART/Melan A, chromogranin A/B, PGP 9.5,
      synaptophysin, MNF116, AE1/AE3, and CD45. Ultrastructurally many of the pigmented
      cells had features typical of melanocytes while a smaller number appeared to be
      melanophages. CONCLUSIONS: Ocular melanosis in Cairn Terriers is characterized by
      an infiltration of pigment-laden cells predominantly, but not exclusively, within
      the anterior uvea and anterior sclera. Most of these cells appear to be
      melanocytes although a variable proportion are pigment-laden melanophages.

PMID- 18638354
TI  - Corneal squamous cell carcinoma in a dog: a case report.
AB  - PURPOSE: To report a case of primary corneal squamous cell carcinoma (SCC) in an
      English Bulldog. In addition, immunohistochemistry of the corneal tissue mass was
      performed using a panel of antibodies. A prominent feature of the present case
      was the clinical history of chronic keratitis due to eyelid abnormalities.
      RESULTS: No papillomavirus antigen was detected in section of normal or
      neoplastic corneal tissue. The corneal epithelial cells were positive for
      pancytokeratins AE1/AE3 and MNF116, and E-cadherin. The neoplastic cells in close
      proximity to the normal epithelial lining were positive for both pancytokeratins
      and E-cadherin with gradual loss of staining toward the center of the neoplastic
      mass. Rare neoplastic cells demonstrated positive staining for caspase 3 and a
      large number was strongly positive for GADD45 and p53. CONCLUSION AND DISCUSSION:
      The observed loss of the various cytokeratins, the strong p53 expression, and low
      numbers of caspase 3 positive cells were suggestive that a p53 mutation may have
      caused this primary corneal SCC. Over-expression of the tumor-suppressor gene p53
      is likely to be a consequence of ultraviolet radiation exposure. Two factors,
      however, may have played a role in the formation of this primary corneal SCC:
      chronic irritation of the corneal surface (microtrauma) and exposure to UV
      radiation.

PMID- 18638355
TI  - Heterologous penetrating keratoplasty for treatment of a corneal sequestrum in a
      cat.
AB  - A corneal sequestrum was diagnosed in an 8-year-old, neutered male Burmese cat. A
      heterologous penetrating keratoplasty (PK) (fresh canine corneal tissue) was
      performed to restore a clear visual axis. A heterograft was selected in order to
      decrease the risk of viral transmission as a screened donor was not available.
      One month postoperatively the graft was vascularized and opaque. The owner failed
      to return for recheck examinations until 16 months postoperatively at which time
      only a faint central nebula remained.

PMID- 18638357
TI  - Breathing easier--good news from air medicine.
AB  - Safety in transport is a major concern. Air medical crashes are in the public
      eye, but a greater risk of transport may be in the clinical care provided along
      the way. While the media focuses on the drama of helicopters landing on scene,
      the greatest and most common risk actually occurs during inter-hospital
      transport. For too long, transport has been a black hole in clinical medicine and
      the real rate of adverse events is unknown. New work from the University of
      Pennsylvania should make us all breathe a little easier.

PMID- 18638356
TI  - Bench-to-bedside review: latest results in hemorrhagic shock.
AB  - Hemorrhagic shock is a leading cause of death in trauma patients worldwide.
      Bleeding control, maintenance of tissue oxygenation with fluid resuscitation,
      coagulation support, and maintenance of normothermia remain mainstays of therapy
      for patients with hemorrhagic shock. Although now widely practised as standard in
      the USA and Europe, shock resuscitation strategies involving blood replacement
      and fluid volume loading to regain tissue perfusion and oxygenation vary between
      trauma centers; the primary cause of this is the scarcity of published evidence
      and lack of randomized controlled clinical trials. Despite enormous efforts to
      improve outcomes after severe hemorrhage, novel strategies based on experimental
      data have not resulted in profound changes in treatment philosophy. Recent
      clinical and experimental studies indicated the important influences of sex and
      genetics on pathophysiological mechanisms after hemorrhage. Those findings might
      provide one explanation why several promising experimental approaches have failed
      in the clinical arena. In this respect, more clinically relevant animal models
      should be used to investigate pathophysiology and novel treatment approaches.
      This review points out new therapeutic strategies, namely immunomodulation,
      cardiovascular maintenance, small volume resuscitation, and so on, that have been
      introduced in clinics or are in the process of being transferred from bench to
      bedside. Control of hemorrhage in the earliest phases of care, recognition and
      monitoring of individual risk factors, and therapeutic modulation of the
      inflammatory immune response will probably constitute the next generation of
      therapy in hemorrhagic shock. Further randomized controlled multicenter clinical
      trials are needed that utilize standardized criteria for enrolling patients, but
      existing ethical requirements must be maintained.

PMID- 18638358
TI  - Genomics technology for assessing soil pollution.
AB  - Transcription and metabolite analysis is a powerful way to reveal physiological
      shifts in response to environmental pollution. Recent studies on earthworms,
      including one in BMC Biology, show that the type of pollution and its
      availability for uptake by organisms can differentially affect transcription and
      metabolism.

PMID- 18638359
TI  - The ethics of characterizing difference: guiding principles on using racial
      categories in human genetics.
AB  - We are a multidisciplinary group of Stanford faculty who propose ten principles
      to guide the use of racial and ethnic categories when characterizing group
      differences in research into human genetic variation.

PMID- 18638360
TI  - Mathematical models in mammalian cell biology.
AB  - A report on the Conference on Systems Biology of Mammalian Cells, Dresden,
      Germany, 22-24 May 2008.

PMID- 18638361
TI  - Corticosteroids for community-acquired pneumonia: time to act!
AB  - The use of corticosteroids for the treatment of community-acquired pneumonia has
      been reported for almost 50 years. A recent systematic analysis of the relevant
      literature suggested that corticosteroids reduce the critical illness associated
      with community-acquired pneumonia. There is little doubt that a prolonged
      administration of a moderate dose of corticosteroids may alleviate the systemic
      inflammatory response and subsequent organ dysfunction in severe infection.
      Whether these favorable effects on morbidity may translate into better survival
      and quality of life needs to be addressed in additional adequately powered
      randomized controlled trials.

PMID- 18638362
TI  - Pandemic influenza: are we prepared to face our obligations?
AB  - After decades of low personal risk for contracting lethal diseases, physicians
      are suddenly facing the possibility of a substantial increase in occupational
      risk during an influenza pandemic. If they are not confronted before the onset of
      an influenza pandemic, feelings of unease and fear or ignorance about physicians'
      professional obligations could profoundly hinder individual physicians in
      fulfilling their professional duties. Such feelings could therefore undermine
      institutional and societal preparations. In their review published in Critical
      Care, Anantham and coworkers outline the ethical framework that forms the basis
      of the professional obligations of physicians who respond to health care
      emergencies, such as an influenza pandemic.

PMID- 18638363
TI  - How to prevent leaky vessels during reperfusion? Just keep that glycocalyx
      sealant in place!
AB  - Myocardial edema is a hallmark of ischemia-reperfusion-related cardiac injury.
      Ischemia-reperfusion has been shown to result in degradation of the endothelial
      glycocalyx. The glycocalyx is the gel-like mesh of polysaccharide structures and
      absorped plasma proteins on the luminal side of the vasculature, and in the past
      decade has been shown to play an important role in protection of the vessel wall,
      including its barrier properties. Prevention of glycocalyx loss or restoration of
      a damaged glycocalyx may be a promising therapeutic target during clinical
      procedures involving ischemia-reperfusion.

PMID- 18638365
TI  - Rift Valley fever virus structural proteins: expression, characterization and
      assembly of recombinant proteins.
AB  - BACKGROUND: Studies on Rift Valley Fever Virus (RVFV) infection process and
      morphogenesis have been hampered due to the biosafety conditions required to
      handle this virus, making alternative systems such as recombinant virus-like
      particles, that may facilitate understanding of these processes are highly
      desirable. In this report we present the expression and characterization of RVFV
      structural proteins N, Gn and Gc and demonstrate the efficient generation of RVFV
      virus-like particles (VLPs) using a baculovirus expression system. RESULTS: A
      recombinant baculovirus, expressing nucleocapsid (N) protein of RVFV at high
      level under the control of the polyhedrin promoter was generated. Gel filtration
      analysis indicated that expressed N protein could form complex multimers.
      Further, N protein complex when visualized by electron microscopy (EM) exhibited
      particulate, nucleocapsid like-particles (NLPs). Subsequently, a single
      recombinant virus was generated that expressed the RVFV glycoproteins (Gn/Gc)
      together with the N protein using a dual baculovirus vector. Both the Gn and Gc
      glycoproteins were detected not only in the cytoplasm but also on the cell
      surface of infected cells. Moreover, expression of the Gn/Gc in insect cells was
      able to induce cell-cell fusion after a low pH shift indicating the retention of
      their functional characteristics. In addition, assembly of these three structural
      proteins into VLPs was identified by purification of cells' supernatant through
      potassium tartrate-glycerol gradient centrifugation followed by EM analysis. The
      purified particles exhibited enveloped structures that were similar to the
      structures of the wild-type RVFV virion particle. In parallel, a second
      recombinant virus was constructed that expressed only Gc protein together with N
      protein. This dual recombinant virus also generated VLPs with clear spiky
      structures, but appeared to be more pleomorphic than the VLPs with both
      glycoproteins, suggesting that Gc and probably also Gn interacts with N protein
      complex independent of each other. CONCLUSION: Our results suggest that
      baculovirus expression system has enormous potential to produce large amount of
      VLPs that may be used both for fundamental and applied research of RVFV.

PMID- 18638364
TI  - Transcription factor control of growth rate dependent genes in Saccharomyces
      cerevisiae: a three factor design.
AB  - BACKGROUND: Characterization of cellular growth is central to understanding
      living systems. Here, we applied a three-factor design to study the relationship
      between specific growth rate and genome-wide gene expression in 36 steady-state
      chemostat cultures of Saccharomyces cerevisiae. The three factors we considered
      were specific growth rate, nutrient limitation, and oxygen availability. RESULTS:
      We identified 268 growth rate dependent genes, independent of nutrient limitation
      and oxygen availability. The transcriptional response was used to identify key
      areas in metabolism around which mRNA expression changes are significantly
      associated. Among key metabolic pathways, this analysis revealed de novo
      synthesis of pyrimidine ribonucleotides and ATP producing and consuming reactions
      at fast cellular growth. By scoring the significance of overlap between growth
      rate dependent genes and known transcription factor target sets, transcription
      factors that coordinate balanced growth were also identified. Our analysis shows
      that Fhl1, Rap1, and Sfp1, regulating protein biosynthesis, have significantly
      enriched target sets for genes up-regulated with increasing growth rate. Cell
      cycle regulators, such as Ace2 and Swi6, and stress response regulators, such as
      Yap1, were also shown to have significantly enriched target sets. CONCLUSION: Our
      work, which is the first genome-wide gene expression study to investigate
      specific growth rate and consider the impact of oxygen availability, provides a
      more conservative estimate of growth rate dependent genes than previously
      reported. We also provide a global view of how a small set of transcription
      factors, 13 in total, contribute to control of cellular growth rate. We
      anticipate that multi-factorial designs will play an increasing role in
      elucidating cellular regulation.

PMID- 18638366
TI  - Impact of social ties on self reported health in France: is everyone affected
      equally?
AB  - AIM: To examine the association of social ties and income with self reported
      health, in order to investigate if social ties have a greater impact on the
      health of people on low incomes compared to those financially better off.
      METHODS: A nationally representative cross-sectional study of 5205 French adults
      using data from questionnaires which asked about health, income and relationships
      with family and friends etc. RESULTS: Less than good self-rated health (SRH) is
      twice as frequently reported by people in the lowest income group than those in
      the highest income group. People with low incomes are also more likely to have
      felt alone on the previous day, received no phone call during the last week, have
      no friends, not be a member of a club, and to live alone. Socially isolated
      people report lower SRH. Likelihood ratio tests for interaction vs. main effect
      models were statistically significant for 2 of the measures of social ties,
      borderline for 2 others and non-significant for one. For 4 of the 5 indicators of
      social ties, larger odd ratios show that social isolation is more strongly
      associated with less than good SRH among people on low incomes compared to those
      with a higher income. CONCLUSION: Social isolation is associated with 'less than
      good' self-rated health. This effect appears to be more important for people on a
      low income.

PMID- 18638368
TI  - Normal response inhibition in boys with Tourette syndrome.
AB  - BACKGROUND: Inhibitory deficits are often a matter of debate in the
      pathophysiology of Tourette syndrome (TS). Previous neuropsychological studies on
      behavioral inhibition revealed equivocal results. METHODS: To overcome existing
      shortcomings (e.g. confounders like medication status, comorbid conditions) we
      compared medication naive boys (10-14 years) suffering exclusively from TS with
      age, gender and IQ matched healthy controls using a highly demanding Go/Nogo task
      that controls for novelty effects. RESULTS: The performance did not differ
      between boys with TS and healthy boys. CONCLUSION: In TS normal response
      inhibition performance as measured by a Go/Nogo task can be assumed. However,
      there might be neurophysiological abnormalities in TS possibly related to
      compensatory mechanisms to control for tics. Hence, further studies combining
      neuropsychological and neurophysiological methods (e.g. electroencephalography,
      fMRI) using the same strictly controlled design along the whole range of
      development and tic severity are recommended.

PMID- 18638367
TI  - Health care costs, long-term survival, and quality of life following intensive
      care unit admission after cardiac arrest.
AB  - INTRODUCTION: The purpose of this study was to investigate the costs and health
      status outcomes of intensive care unit (ICU) admission in patients who present
      after sudden cardiac arrest with in-hospital or out-of-hospital cardiopulmonary
      resuscitation. METHODS: Five-year survival, health-related quality of life
      (Medical Outcome Survey Short Form-36 questionnaire, SF-36), ICU costs, hospital
      costs and post-hospital health care costs per survivor, costs per life year
      gained, and costs per quality-adjusted life year gained of patients admitted to a
      single ICU were assessed. RESULTS: One hundred ten of 354 patients (31%) were
      alive 5 years after hospital discharge. The mean health status index of 5-year
      survivors was 0.77 (95% confidence interval 0.70 to 0.85). Women rated their
      health-related quality of life significantly better than men did (0.87 versus
      0.74; P < 0.05). Costs per hospital discharge survivor were 49,952 euro.
      Including the costs of post-hospital discharge health care incurred during their
      remaining life span, the total costs per life year gained were 10,107 euro.
      Considering 5-year survivors only, the costs per life year gained were calculated
      as 9,816 euro or 14,487 euro per quality-adjusted life year gained. Including
      seven patients with severe neurological sequelae, costs per life year gained in 5
      year survivors increased by 18% to 11,566 euro. CONCLUSION: Patients who leave
      the hospital following cardiac arrest without severe neurological disabilities
      may expect a reasonable quality of life compared with age- and gender-matched
      controls. Quality-adjusted costs for this patient group appear to be within
      ranges considered reasonable for other groups of patients.

PMID- 18638369
TI  - FISH mapping of Philadelphia negative BCR/ABL1 positive CML.
AB  - BACKGROUND: Chronic myeloid leukaemia (CML) is a haematopoietic stem cell
      disorder, almost always characterized by the presence of the Philadelphia
      chromosome (Ph), usually due to t(9;22)(q34;q11) or its variants. The Ph results
      in the formation of the BCR/ABL1 fusion gene, which is a constitutively activated
      tyrosine kinase. Around 1% of CML patients appear to have a Ph negative karyotype
      but carry a cryptic BCR/ABL1 fusion that can be located by fluorescence in situ
      hybridisation (FISH) at chromosome 22q11, 9q34 or a third chromosome. Here we
      present FISH mapping data of BCR and ABL1 flanking regions and associated
      chromosomal rearrangements in 9 Ph negative BCR/ABL1 positive CML patients plus
      the cell line CML-T1. RESULTS: BCR/ABL1 was located at 9q34 in 3 patients, 22q11
      in 5 patients and CML-T1 and 22p11 in 1 patient. In 3 of 6 cases with the fusion
      at 22q11 a distal breakpoint cluster was found within a 280 Kb region containing
      the RAPGEF1 gene, while in another patient and the CML-T1 the distal breakpoint
      fell within a single BAC clone containing the 3' RXRA gene. Two cases had a
      duplication of the masked Ph while genomic deletions of the flanking regions were
      identified in 3 cases. Even more complex rearrangements were found in 3 further
      cases. CONCLUSION: BCR/ABL1 formation resulted from a direct insertion (one step
      mechanism) in 6 patients and CML-T1, while in 3 patients the fusion gene
      originated from a sequence of rearrangements (multiple steps). The presence of
      different rearrangements of both 9q34 and 22q11 regions highlights the genetic
      heterogeneity of this subgroup of CML. Future studies should be performed to
      confirm the presence of true breakpoint hot spots and assess their implications
      in Ph negative BCR/ABL1 positive CML.

PMID- 18638370
TI  - The level of hypotension during hemorrhagic shock is a major determinant of the
      post-resuscitation systemic inflammatory response: an experimental study.
AB  - BACKGROUND: To evaluate whether the level of hypotension during hemorrhagic shock
      may influence the oxidative and inflammatory responses developed during post
      ischemic resuscitation. METHODS: Fifteen rabbits were equally allocated into
      three groups: sham-operated (group sham); bled within 30 minutes to mean arterial
      pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30
      mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was
      performed by reinfusing shed blood with two volumes of Ringer's lactate and blood
      was sampled for estimation of serum levels aminotransferases, creatinine, TNF
      alpha, IL-1beta, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS)
      and for the determination of oxidative burst of polymorhonuclears (PMNs) and
      mononuclear cells (MCs). RESULTS: Serum AST of group shock-30 was higher than
      that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum
      creatinine of group shock-30 was higher than group shock-40 at 120 minutes.
      Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and
      shock-30 were higher than group sham within the first 60 minutes after start of
      resuscitation. Serum concentrations of IL-1beta, IL-6 and TNF-alpha of group
      shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No
      differences were found between two groups regarding serum MDA and TAS and
      oxidative burst on PMNs and MCs but both groups were different to group sham.
      CONCLUSION: The level of hypotension is a major determinant of the severity of
      hepatic and renal dysfunction and of the inflammatory response arising during
      post-ischemic hemorrhagic shock resuscitation. These findings deserve further
      evaluation in the clinical setting.

PMID- 18638372
TI  - Transient left ventricular apical ballooning and exercise induced hypertension
      during treadmill exercise testing: is there a common hypersympathetic mechanism?
AB  - OBJECTIVE: To describe two cases of Takotsubo like myocardial contractile pattern
      during exercise stress test secondary to hypertensive response. BACKGROUND:
      Treadmill exercise testing is known to cause sympathetic stimulation, leading to
      increased levels of catecholamine, resulting in alteration in vascular tone.
      Hypertensive response during exercise testing can cause abnormal consequences,
      resulting in false positive results. CASES: We present the cases of two patients
      experiencing apical and basal akinesis during exercise stress echocardiography,
      in whom normal wall motion response was observed on subsequent pharmacologic
      stress testing. The first patient developed transient left ventricular (LV)
      apical akinesis during exercise stress echocardiography. Due to high suspicion
      that this abnormality might be secondary to hypertensive response, pharmacologic
      stress testing was performed after three days, which was completely normal and
      showed no such wall motion abnormality. Qualitative assessment of myocardial
      perfusion using contrast was also performed, which showed good myocardial blood
      flow, indicating low probability for significant obstructive coronary artery
      disease. The second patient developed LV basal akinesis as a result of
      hypertensive response during exercise testing. Coronary angiogram was not
      performed in either patient due to low suspicion for coronary artery disease, and
      subsequently negative stress studies. RESULTS: Transient stress induced
      cardiomyopathy can develop secondary to hypertensive response during exercise
      stress testing. CONCLUSION: These cases provide supporting evidence to the hyper
      sympathetic theory of left ventricular ballooning syndrome.

PMID- 18638371
TI  - Genomic actions of 1,25-dihydroxyvitamin D3 on insulin receptor gene expression,
      insulin receptor number and insulin activity in the kidney, liver and adipose
      tissue of streptozotocin-induced diabetic rats.
AB  - BACKGROUND: this study set out to examine the effects of the treatment with 1,25
      dihydroxyvitamin D3 (1,25D3) [150 IU/Kg (3.75 microg/Kg) one a day, for 15 days]
      to non-diabetic rats and in rats rendered diabetic by a single injection of
      streptozotocin [65 mg/kg]. RESULTS: treatment with 1,25D3 to non-diabetic rats
      did not affect the biochemical parameters measured in the plasma and urine of
      these animals. Likewise, insulin receptor expression in the kidney, liver, or
      adipose tissue and insulin-stimulated glucose transport in adipocytes from these
      animals were not affected either. Treatment with 1,25D3 to streptozotocin-induced
      diabetic rats did not correct the hyperglycemia, hypoinsulinemia, glycosuria or
      ketonemia induced by the diabetes, although it partially reversed the over
      expression of the insulin receptor gene in the liver and adipose tissue, without
      altering the normal expression of this gene in the kidney. These effects were
      accompanied by a normalization of the number of insulin receptors without
      altering receptor affinity but improving the insulin response to glucose
      transport in adipocytes from these diabetic animals. Moreover, a computer search
      in the rat insulin receptor promoter revealed the existence of two candidate
      vitamin D response element (VDRE) sequences located at -256/-219 bp and -653/-620
      bp, the first overlapped by three and the second by four AP-2-like sites.
      CONCLUSION: these genomic actions of 1,25D3 could represent beneficial effects
      associated with the amelioration of diabetes via mechanisms that possibly involve
      direct transcriptional activation of the rat insulin receptor gene. The candidate
      VDREs identified may respond to 1,25D3 via activation of the vitamin D receptor,
      although this remains to be investigated.

PMID- 18638373
TI  - Epigenetic mapping and functional analysis in a breast cancer metastasis model
      using whole-genome promoter tiling microarrays.
AB  - INTRODUCTION: Breast cancer metastasis is a complex, multi-step biological
      process. Genetic mutations along with epigenetic alterations in the form of DNA
      methylation patterns and histone modifications contribute to metastasis-related
      gene expression changes and genomic instability. So far, these epigenetic
      contributions to breast cancer metastasis have not been well characterized, and
      there is only a limited understanding of the functional mechanisms affected by
      such epigenetic alterations. Furthermore, no genome-wide assessments have been
      undertaken to identify altered DNA methylation patterns in the context of
      metastasis and their effects on specific functional pathways or gene networks.
      METHODS: We have used a human gene promoter tiling microarray platform to analyze
      a cell line model of metastasis to lymph nodes composed of a poorly metastatic
      MDA-MB-468GFP human breast adenocarcinoma cell line and its highly metastatic
      variant (468LN). Gene networks and pathways associated with metastasis were
      identified, and target genes associated with epithelial-mesenchymal transition
      were validated with respect to DNA methylation effects on gene expression.
      RESULTS: We integrated data from the tiling microarrays with targets identified
      by Ingenuity Pathways Analysis software and observed epigenetic variations in
      genes implicated in epithelial-mesenchymal transition and with tumor cell
      migration. We identified widespread genomic hypermethylation and hypomethylation
      events in these cells and we confirmed functional associations between
      methylation status and expression of the CDH1, CST6, EGFR, SNAI2 and ZEB2 genes
      by quantitative real-time PCR. Our data also suggest that the complex genomic
      reorganization present in cancer cells may be superimposed over promoter-specific
      methylation events that are responsible for gene-specific expression changes.
      CONCLUSION: This is the first whole-genome approach to identify genome-wide and
      gene-specific epigenetic alterations, and the functional consequences of these
      changes, in the context of breast cancer metastasis to lymph nodes. This approach
      allows the development of epigenetic signatures of metastasis to be used
      concurrently with genomic signatures to improve mapping of the evolving molecular
      landscape of metastasis and to permit translational approaches to target
      epigenetically regulated molecular pathways related to metastatic progression.

PMID- 18638374
TI  - Regionally and climatically restricted patterns of distribution of genetic
      diversity in a migratory bat species, Miniopterus schreibersii (Chiroptera:
      Vespertilionidae).
AB  - BACKGROUND: Various mechanisms such as geographic barriers and glacial episodes
      have been proposed as determinants of intra-specific and inter-specific
      differentiation of populations, and the distribution of their genetic diversity.
      More recently, habitat and climate differences, and corresponding adaptations
      have been shown to be forces influencing the phylogeographic evolution of some
      vertebrates. In this study, we examined the contribution of these various factors
      on the genetic differentiation of the bent-winged bat, Miniopterus schreibersii,
      in southeastern Europe and Anatolia. RESULTS AND CONCLUSION: Our results showed
      differentiation in mitochondrial DNA coupled with weaker nuclear differentiation.
      We found evidence for restriction of lineages to geographical areas for hundreds
      of generations. The results showed that the most likely ancestral haplotype was
      restricted to the same geographic area (the Balkans) for at least 6,000 years. We
      were able to delineate the migration routes during the population expansion
      process, which followed the coasts and the inland for different nested
      mitochondrial clades. Hence, we were able to describe a scenario showing how
      multiple biotic and abiotic events including glacial periods, climate and
      historical dispersal patterns complemented each other in causing regional and
      local differentiation within a species.

PMID- 18638375
TI  - Penile and scrotal strangulation caused by a steel ring: a case report.
AB  - Application of constricting devices on the external male genitalia for
      increasing sexual performance is an unusual practice that can potentially lead to
      penile strangulation with severe consequences. In this case report we describe a
      case of a 48 year old male who presented in our hospital with a steel ring on his
      external genitalia which led to penile strangulation and a short review of the
      literature. The foreign body was successfully removed by an angle grinder which
      was not immediately available in the operating theatre. The patient had an
      uneventful recovery.

PMID- 18638377
TI  - The effect of maternal anthropometric characteristics and social factors on
      gestational age and birth weight in Sudanese newborn infants.
AB  - BACKGROUND: In Africa low birth weight (LBW) (<2500 g), is the strongest
      determinant of infant morbidity and mortality. The aim of this study was to
      quantify the effect of maternal anthropometry, education and socio-economic
      status on gestational age and birth weight. METHODS: In 1000 Sudanese mothers
      with singleton births, anthropometric measurements (weight, height, mid-arm
      circumference) and newborn birth weight were taken within 24 hours of delivery.
      Furthermore, maternal education and socio-economic status were recorded. The
      effect of these maternal variables on gestational age and birth weight was
      investigated by receiver operating characteristic (ROC) curves and by
      multivariate logistic regression analysis. RESULTS: Although maternal height was
      significantly correlated (p = 0.002) with gestational age, we did not find
      maternal characteristics of value in determining the risk for preterm birth.
      Birth order was the strongest determinant of birth weight compared to other
      maternal characteristics. The LBW rate of first born babies of 12.2% was nearly
      twice that of infants of multiparous mothers. Maternal age and all maternal
      anthropometric measurements were positively correlated (p < 0.001) with birth
      weight. A maternal height of <156 cm, a maternal weight of <66 kg, a maternal mid
      arm circumference of <27 cm and years of education of </= 8 years were found to
      increase the relative risk of LBW but this was statistically significant only in
      the case of maternal height. Maternal age and BMI had no statistically
      significant effect on determining the risk for LBW. The social class did not
      affect the birth weight, while the number of years of education was positively
      correlated with birth weight (p = 0.01). The LBW rate decreased from 9.2% for </=
      8 years of education to 6.0% for >12 years of education. CONCLUSION: Birth order
      and maternal height were found to be the most important maternal parameters which
      influences birth weight and the risk for LBW. The duration of maternal education
      and not social class was found to significantly affect the risk for LBW.

PMID- 18638376
TI  - The molecular basis of color vision in colorful fish: four long wave-sensitive
      (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid
      substitutions at key functional sites.
AB  - BACKGROUND: Comparisons of functionally important changes at the molecular level
      in model systems have identified key adaptations driving isolation and
      speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins
      appear to play a role in mate choice and male color variation within and among
      species. To test the hypothesis that the evolution of elaborate coloration in
      male guppies (Poecilia reticulata) is also associated with opsin gene diversity,
      we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the
      family Poeciliidae. RESULTS: Sequences of four LWS opsin genes were amplified
      from the guppy genome and from mRNA isolated from adult guppy eyes. Variation in
      expression was quantified using qPCR. Three of the four genes encode opsins
      predicted to be most sensitive to different wavelengths of light because they
      vary at key amino acid positions. This family of LWS opsin genes was produced by
      a diversity of duplication events. One, an intronless gene, was produced prior to
      the divergence of families Fundulidae and Poeciliidae. Between-gene PCR and DNA
      sequencing show that two of the guppy LWS opsins are linked in an inverted
      orientation. This inverted tandem duplication event occurred near the base of the
      poeciliid tree in the common ancestor of Poecilia and Xiphophorus. The fourth
      sequence has been uncovered only in the genus Poecilia. In the guppies surveyed
      here, this sequence is a hybrid, with the 5' end most similar to one of the
      tandem duplicates and the 3' end identical to the other. CONCLUSION: Enhanced
      wavelength discrimination, a possible consequence of opsin gene duplication and
      divergence, might have been an evolutionary prerequisite for color-based sexual
      selection and have led to the extraordinary coloration now observed in male
      guppies and in many other poeciliids.

PMID- 18638378
TI  - Analysis of variants in DNA damage signalling genes in bladder cancer.
AB  - BACKGROUND: Chemicals from occupational exposure and components of cigarette
      smoke can cause DNA damage in bladder urothelium. Failure to repair DNA damage by
      DNA repair proteins may result in mutations leading to genetic instability and
      the development of bladder cancer. Immunohistochemistry studies have shown DNA
      damage signal activation in precancerous bladder lesions which is lost on
      progression, suggesting that the damage signalling mechanism acts as a brake to
      further tumorigenesis. Single nucleotide polymorphisms (SNPs) in DSB signalling
      genes may alter protein function. We hypothesized that SNPs in DSB signalling
      genes may modulate predisposition to bladder cancer and influence the effects of
      environmental exposures. METHODS: We recruited 771 cases and 800 controls (573
      hospital-based and 227 population-based from a previous case-control study) and
      interviewed them regarding their smoking habits and occupational history. DNA was
      extracted from a peripheral blood sample and genotyping of 24 SNPs in MRE11,
      NBS1, RAD50, H2AX and ATM was undertaken using an allelic discrimination method
      (Taqman). RESULTS: Smoking and occupational dye exposure were strongly associated
      with bladder cancer risk. Using logistic regression adjusting for age, sex,
      smoking and occupational dye exposure, there was a marginal increase in risk of
      bladder cancer for an MRE11 3'UTR SNP (rs2155209, adjusted odds ratio 1.54 95% CI
      (1.13-2.08, p = 0.01) for individuals homozygous for the rare allele compared to
      those carrying the common homozygous or heterozygous genotype). However, in the
      hospital-based controls, the genotype distribution for this SNP deviated from
      Hardy-Weinberg equilibrium. None of the other SNPs showed an association with
      bladder cancer and we did not find any significant interaction between any of
      these polymorphisms and exposure to smoking or dye exposure. CONCLUSION: Apart
      from a possible effect for one MRE11 3'UTR SNP, our study does not support the
      hypothesis that SNPs in DSB signaling genes modulate predisposition to bladder
      cancer.

PMID- 18638381
TI  - Antibodies to the CD4-binding site of HIV-1 gp120 suppress gp120-specific CD4 T
      cell response while enhancing antibody response.
AB  - BACKGROUND: The binding of Abs to the CD4-binding site (CD4bs) of HIV-1 envelope
      gp120 has been shown to obstruct the processing and generation of helper epitopes
      from this antigen, resulting in poor presentation of various gp120 epitopes by
      MHC class II to CD4 T cells. However, the physiologic significance of these
      inhibitory anti-CD4bs Abs in vivo has remained unclear. In this study, we
      evaluated the immunologic effects of anti-CD4bs Abs in vivo using a murine model.
      RESULTS: Animals were immunized with recombinant envelope proteins with or
      without CD4-binding activity (designated CD4bs+ Env and CD4bs- Env,
      respectively). As expected, anti-CD4bs Abs were generated only after immunization
      with CD4bs+ Env and not with CD4bs- Env. The presence of anti-CD4bs Abs was
      associated with lower levels of envelope-specific lymphoproliferation in animals
      immunized with CD4bs+ Env. To further determine the specific role of the anti
      CD4bs Abs, we immunized mice with gp120 in the presence of an inhibitory anti
      CD4bs mAb or a non-inhibitory anti-gp120 mAb. The data show that the presence of
      anti-CD4bs mAb reduced CD4 T cell responses to gp120. However, we also detected
      significantly higher titers of anti-gp120 Abs following immunization with gp120
      and the anti-CD4bs mAb. CONCLUSION: Anti-CD4bs Abs can exert discordant effects
      on the gp120-specific CD4 T cell and Ab responses in vivo, indicating the
      importance of these particular Abs in influencing both the cellular and the
      humoral immune responses against HIV-1.

PMID- 18638380
TI  - The omega-3 fatty acid, eicosapentaenoic acid (EPA), prevents the damaging
      effects of tumour necrosis factor (TNF)-alpha during murine skeletal muscle cell
      differentiation.
AB  - BACKGROUND: Eicosapentaenoic acid (EPA) is a omega-3 polyunsaturated fatty acid
      with anti-inflammatory and anti-cachetic properties that may have potential
      benefits with regards to skeletal muscle atrophy conditions where inflammation is
      present. It is also reported that pathologic levels of the pro-inflammatory
      cytokine tumour necrosis factor (TNF)-alpha are associated with muscle wasting,
      exerted through inhibition of myogenic differentiation and enhanced apoptosis.
      These findings led us to hypothesize that EPA may have a protective effect
      against skeletal muscle damage induced by the actions of TNF-alpha. RESULTS: The
      deleterious effects of TNF-alpha on C2C12 myogenesis were completely inhibited by
      co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC
      expression and significantly increased myogenic fusion (p < 0.05) and myotube
      diameter (p < 0.05) indices back to control levels. EPA protective activity was
      associated with blocking cell death pathways as EPA completely attenuated TNF
      mediated increases in caspase-8 activity (p < 0.05) and cellular necrosis (p <
      0.05) back to their respective control levels. EPA alone significantly reduced
      spontaneous apoptosis and necrosis of differentiating myotubes (p < 0.001 and p <
      0.05, respectively). A 2 hour pre-treatment with EPA, prior to treatment with TNF
      alone, gave similar results. CONCLUSION: In conclusion, EPA has a protective
      action against the damaging effects of TNF-alpha on C2C12 myogenesis. These
      findings support further investigations of EPA as a potential therapeutic agent
      during skeletal muscle regeneration following injury.

PMID- 18638379
TI  - Modulation of gene expression in drug resistant Leishmania is associated with
      gene amplification, gene deletion and chromosome aneuploidy.
AB  - BACKGROUND: Drug resistance can be complex, and several mutations responsible for
      it can co-exist in a resistant cell. Transcriptional profiling is ideally suited
      for studying complex resistance genotypes and has the potential to lead to novel
      discoveries. We generated full genome 70-mer oligonucleotide microarrays for all
      protein coding genes of the human protozoan parasites Leishmania major and
      Leishmania infantum. These arrays were used to monitor gene expression in
      methotrexate resistant parasites. RESULTS: Leishmania is a eukaryotic organism
      with minimal control at the level of transcription initiation and few genes were
      differentially expressed without concomitant changes in DNA copy number. One
      exception was found in Leishmania major, where the expression of whole
      chromosomes was down-regulated. The microarrays highlighted several mechanisms by
      which the copy number of genes involved in resistance was altered; these include
      gene deletion, formation of extrachromosomal circular or linear amplicons, and
      the presence of supernumerary chromosomes. In the case of gene deletion or gene
      amplification, the rearrangements have occurred at the sites of repeated (direct
      or inverted) sequences. These repeats appear highly conserved in both species to
      facilitate the amplification of key genes during environmental changes. When
      direct or inverted repeats are absent in the vicinity of a gene conferring a
      selective advantage, Leishmania will resort to supernumerary chromosomes to
      increase the levels of a gene product. CONCLUSION: Aneuploidy has been suggested
      as an important cause of drug resistance in several organisms and additional
      studies should reveal the potential importance of this phenomenon in drug
      resistance in Leishmania.

PMID- 18638382
TI  - The Sertindole Safety Survey: a retrospective analysis under a named patient use
      programme in Europe.
AB  - BACKGROUND: After sertindole's suspension, health authorities established a
      specific named-patient use (NPU) programme in order to supply sertindole to
      patients who did not respond to or did not tolerate alternative treatments. This
      programme provided the possibility of prospectively following an exhaustive
      cohort of patients treated with sertindole after its suspension. A survey was
      performed to assess sertindole's modalities of prescription, assess and document
      any serious adverse events (SAEs), and assess the mortality rate within the NPU
      cohort. METHODS: The study comprised a survey of sertindole-treated patients in
      eleven European countries. All patients treated with sertindole within the NPU
      programme were eligible for the study. RESULTS: 1,432 patients were included in
      the study. The reason for sertindole prescription was lack of efficacy
      (approximately 50%) or adverse events (approximately 20%) of other antipsychotic
      treatments. The mean sertindole dose was 13.4 mg daily. Lack of efficacy and
      adverse events were reported as reasons for sertindole discontinuation.A total of
      97 SAEs were recorded, including ten fatal outcomes, which occurred during the
      study period or within thirty days after sertindole discontinuation. The all
      cause mortality rate was 0.51 per 100 Person-Years of Exposure (95% Poisson
      confidence interval: 0.23-0.97). QTc prolongation was reported in 15 patients
      (1.05% of total patients), being a rate of 0.85 per 100 Person-Years of Exposure
      [95% CI: 0.48-1.41]. CONCLUSION: Although prescribing and supplying sertindole
      were subject to administrative constraints, a significant number of patients were
      treated with sertindole, thus supporting the need for sertindole in specific
      cases. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 18638383
TI  - Overexpression of cathepsin K in mice decreases collagen deposition and lung
      resistance in response to bleomycin-induced pulmonary fibrosis.
AB  - BACKGROUND: Lung fibrosis is a devastating pulmonary disorder characterized by
      alveolar epithelial injury, extracellular matrix deposition and scar tissue
      formation. Due to its potent collagenolytic activity, cathepsin K, a lysosomal
      cysteine protease is an interesting target molecule with therapeutic potential to
      attenuate bleomycin-induced pulmonary fibrosis in mice. We here tested the
      hypothesis that over-expression of cathepsin K in the lungs of mice is protective
      in bleomycin-induced pulmonary fibrosis. METHODS: Wild-type and cathepsin K
      overexpressing (cathepsin K transgenic; cath K tg) mice were challenged
      intratracheally with bleomycin and sacrificed at 1, 2, 3 and 4 weeks post
      treatment followed by determination of lung fibrosis by estimating lung collagen
      content, lung histopathology, leukocytic infiltrates and lung function. In
      addition, changes in cathepsin K protein levels in the lung were determined by
      immunohistochemistry, real time RT-PCR and western blotting. RESULTS: Cathepsin K
      protein levels were strongly increased in alveolar macrophages and lung
      parenchymal tissue of mock-treated cathepsin K transgenic (cath K tg) mice
      relative to wild-type mice and further increased particularly in cath K tg but
      also wild-type mice in response to bleomycin. Moreover, cath K tg mice responded
      with a lower collagen deposition in their lungs, which was accompanied by a
      significantly lower lung resistance (RL) compared to bleomycin-treated wild-type
      mice. In addition, cath K tg mice responded with a lower degree of lung fibrosis
      than wild-type mice, a process that was found to be independent of inflammatory
      leukocyte mobilization in response to bleomycin challenge. CONCLUSION: Over
      expression of cathepsin K reduced lung collagen deposition and improved lung
      function parameters in the lungs of transgenic mice, thereby providing at least
      partial protection against bleomycin-induced lung fibrosis.

PMID- 18638385
TI  - Web GIS in practice VI: a demo playlist of geo-mashups for public health
      neogeographers.
AB  - 'Mashup' was originally used to describe the mixing together of musical tracks to
      create a new piece of music. The term now refers to Web sites or services that
      weave data from different sources into a new data source or service. Using a
      musical metaphor that builds on the origin of the word 'mashup', this paper
      presents a demonstration "playlist" of four geo-mashup vignettes that make use of
      a range of Web 2.0, Semantic Web, and 3-D Internet methods, with outputs/end-user
      interfaces spanning the flat Web (two-dimensional - 2-D maps), a three
      dimensional - 3-D mirror world (Google Earth) and a 3-D virtual world (Second
      Life). The four geo-mashup "songs" in this "playlist" are: 'Web 2.0 and GIS
      (Geographic Information Systems) for infectious disease surveillance', 'Web 2.0
      and GIS for molecular epidemiology', 'Semantic Web for GIS mashup', and 'From
      Yahoo! Pipes to 3-D, avatar-inhabited geo-mashups'. It is hoped that this
      showcase of examples and ideas, and the pointers we are providing to the many
      online tools that are freely available today for creating, sharing and reusing
      geo-mashups with minimal or no coding, will ultimately spark the imagination of
      many public health practitioners and stimulate them to start exploring the use of
      these methods and tools in their day-to-day practice. The paper also discusses
      how today's Web is rapidly evolving into a much more intensely immersive, mixed
      reality and ubiquitous socio-experiential Metaverse that is heavily
      interconnected through various kinds of user-created mashups.

PMID- 18638386
TI  - Paget's disease of the skull causing hyperprolactinemia and erectile dysfunction:
      a case report.
AB  - INTRODUCTION: Hyperprolactinemia is an uncommon cause of erectile dysfunction in
      men. Paget's disease of the skull is a relatively common disease. This case
      proposes a rare example of a causative link between the two and how treatment of
      the Paget's disease with bisphosphonates helped the patient regain erectile
      function. CASE PRESENTATION: A 67-year-old man with Paget's disease of the skull
      presented with prostatitis, erectile dysfunction, and hyperprolactinemia. Radio
      isotope scanning showed increased vascularity around the sphenoid bone. Treatment
      with intravenous bisphosphonates improved the active Paget's disease as indicated
      by declining alkaline phosphatase levels and the patient's erectile function
      while serum prolactin levels became normal and serum testosterone levels remained
      unchanged. CONCLUSION: It is possible that hyperprolactinemia is unrecognised in
      other patients with Paget's disease of the skull. Normalizing elevated prolactin
      levels by using bisphosphonates in treating Paget's disease appears to be more
      appropriate than traditional treatment for hyperprolactinemia.

PMID- 18638384
TI  - The lateral mobility of cell adhesion molecules is highly restricted at septate
      junctions in Drosophila.
AB  - BACKGROUND: A complex of three cell adhesion molecules (CAMs) Neurexin IV(Nrx
      IV), Contactin (Cont) and Neuroglian (Nrg) is implicated in the formation of
      septate junctions between epithelial cells in Drosophila. These CAMs are
      interdependent for their localization at septate junctions and e.g. null mutation
      of nrx IV or cont induces the mislocalization of Nrg to the baso-lateral
      membrane. These mutations also result in ultrastructural alteration of the
      strands of septate junctions and breakdown of the paracellular barrier. Varicose
      (Vari) and Coracle (Cora), that both interact with the cytoplasmic tail of Nrx
      IV, are scaffolding molecules required for the formation of septate junctions.
      RESULTS: We conducted photobleaching experiments on whole living Drosophila
      embryos to analyze the membrane mobility of CAMs at septate junctions between
      epithelial cells. We show that GFP-tagged Nrg and Nrx IV molecules exhibit very
      stable association with septate junctions in wild-type embryos. Nrg-GFP is
      mislocalized to the baso-lateral membrane in nrx IV or cont null mutant embryos,
      and displays increased mobile fraction. Similarly, Nrx IV-GFP becomes distributed
      to the baso-lateral membrane in null mutants of vari and cora, and its mobile
      fraction is strongly increased. The loss of Vari, a MAGUK protein that interacts
      with the cytoplasmic tail of Nrx IV, has a stronger effect than the null mutation
      of nrx IV on the lateral mobility of Nrg-GFP. CONCLUSION: The strands of septate
      junctions display a stable behavior in vivo that may be correlated with their
      role of paracellular barrier. The membrane mobility of CAMs is strongly limited
      when they take part to the multimolecular complex forming septate junctions. This
      restricted lateral diffusion of CAMs depends on both adhesive interactions and
      clustering by scaffolding molecules. The lateral mobility of CAMs is strongly
      increased in embryos presenting alteration of septate junctions. The stronger
      effect of vari by comparison with nrx IV null mutation supports the hypothesis
      that this scaffolding molecule may cross-link different types of CAMs and play a
      crucial role in stabilizing the strands of septate junctions.

PMID- 18638387
TI  - Composition and structure of the parasite faunas of cod, Gadus morhua L.
      (Teleostei: Gadidae), in the North East Atlantic.
AB  - BACKGROUND: Although numerous studies on parasites of the Atlantic cod, Gadus
      morhua L. have been conducted in the North Atlantic, comparative analyses on
      local cod parasite faunas are virtually lacking. The present study is based on
      examination of large samples of cod from six geographical areas of the North East
      Atlantic which yielded abundant baseline data on parasite distribution and
      abundance. MATERIALS AND METHODS: A total of 826 fish was sampled in the Baltic,
      Celtic, Irish and North seas, Icelandic waters and Trondheimsfjord (Norway) in
      2002 (spring and autumn) and 2003 (spring). The gills and internal organs
      (oesophagus, stomach, intestine, pyloric caeca, liver, heart, spleen, gall
      bladder and gonads) were examined for macroparasites following a standardised
      protocol. The taxonomic consistency of the identification was ensured thorough
      the entire study. RESULTS: We discuss some problems in parasite identification,
      outline the composition of the parasite faunas in cod in the six North East
      Atlantic regions, provide novel data on parasite prevalence and abundance and a
      comparative assessment of the structure of the regional parasite faunas with
      respect to the higher-level taxonomic groupings, host specificity and
      zoogeographical distribution of the parasites. Altogether 57 different parasite
      forms were found including seven new host records (Diclidophora merlangi,
      Rhipidocotyle sp., Fellodistomum sp., Steringotrema sp., Cucullanus sp.,
      Spinitectus sp., and Chondracanthus ornatus). The predominant groups of cod
      parasites were trematodes (19 species) and nematodes (13 species) including
      larval anisakids which comprised 58.2% of the total number of individuals.
      CONCLUSION: Our study reveals relatively rich regional parasite faunas in cod
      from the North East Atlantic which are dominated by generalist parasites with
      Arcto-Boreal distribution. Further, it provides more detailed data on the
      distribution in the North East Atlantic of the majority of cod parasites which
      may serve as baselines for future studies on the effect of climate change. Based
      on the faunal comparisons, predictions can be made in relation to the structure
      and diversity of the parasite communities in the North East Atlantic regions
      studied.

PMID- 18638388
TI  - Association study of polymorphisms in the neutral amino acid transporter genes
      SLC1A4, SLC1A5 and the glycine transporter genes SLC6A5, SLC6A9 with
      schizophrenia.
AB  - BACKGROUND: Based on the glutamatergic dysfunction hypothesis for schizophrenia
      pathogenesis, we have been performing systematic association studies of
      schizophrenia with the genes involved in glutametergic transmission. We report
      here association studies of schizophrenia with SLC1A4, SLC1A5 encoding neutral
      amino acid transporters ASCT1, ASCT2, and SLC6A5, SLC6A9 encoding glycine
      transporters GLYT2, GLYT1, respectively. METHODS: We initially tested the
      association of 21 single nucleotide polymorphisms (SNPs) distributed in the four
      gene regions with schizophrenia using 100 Japanese cases-control pairs and
      examined allele, genotype and haplotype association with schizophrenia. The
      observed nominal significance were examined in the full-size samples (400 cases
      and 420 controls). RESULTS: We observed nominally significant single-marker
      associations with schizophrenia in SNP2 (P = 0.021) and SNP3 (P = 0.029) of
      SLC1A4, SNP1 (P = 0.009) and SNP2 (P = 0.022) of SLC6A5. We also observed
      nominally significant haplotype associations with schizophrenia in the
      combinations of SNP2-SNP7 (P = 0.037) of SLC1A4 and SNP1-SNP4 (P = 0.043) of
      SLC6A5. We examined all of the nominal significance in the Full-size Sample Set,
      except one haplotype with insufficient LD. The significant association of SNP1 of
      SLC6A5 with schizophrenia was confirmed in the Full-size Sample Set (P = 0.018).
      CONCLUSION: We concluded that at least one susceptibility locus for schizophrenia
      may be located within or nearby SLC6A5, whereas SLC1A4, SLC1A5 and SLC6A9 are
      unlikely to be major susceptibility genes for schizophrenia in the Japanese
      population.

PMID- 18638390
TI  - The speciation of the proteome.
AB  - INTRODUCTION: In proteomics a paradox situation developed in the last years. At
      one side it is basic knowledge that proteins are post-translationally modified
      and occur in different isoforms. At the other side the protein expression concept
      disclaims post-translational modifications by connecting protein names directly
      with function. DISCUSSION: Optimal proteome coverage is today reached by bottom
      up liquid chromatography/mass spectrometry. But quantification at the peptide
      level in shotgun or bottom-up approaches by liquid chromatography and mass
      spectrometry is completely ignoring that a special peptide may exist in an
      unmodified form and in several-fold modified forms. The acceptance of the protein
      species concept is a basic prerequisite for meaningful quantitative analyses in
      functional proteomics. In discovery approaches only top-down analyses, separating
      the protein species before digestion, identification and quantification by two
      dimensional gel electrophoresis or protein liquid chromatography, allow the
      correlation between changes of a biological situation and function. CONCLUSION:
      To obtain biological relevant information kinetics and systems biology have to be
      performed at the protein species level, which is the major challenge in
      proteomics today.

PMID- 18638389
TI  - The MOBILIZE Boston Study: design and methods of a prospective cohort study of
      novel risk factors for falls in an older population.
AB  - BACKGROUND: Falls are the sixth leading cause of death in elderly people in the
      U.S. Despite progress in understanding risk factors for falls, many suspected
      risk factors have not been adequately studied. Putative risk factors for falls
      such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot
      disorders are poorly understood, in part because they pose measurement
      challenges, particularly for large observational studies. METHODS: The MOBILIZE
      Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study
      of a unique set of risk factors for falls in seniors in the Boston area. Using a
      door-to-door population-based recruitment, we have enrolled 765 persons aged 70
      and older. The baseline assessment was conducted in 2 segments: a 3-hour home
      interview followed within 4 weeks by a 3-hour clinic examination. Measures
      included pain, cerebral hemodynamics, and foot disorders as well as established
      fall risk factors. For the falls follow-up, participants return fall calendar
      postcards to the research center at the end of each month. Reports of falls are
      followed-up with a telephone interview to assess circumstances and consequences
      of each fall. A second assessment is performed 18 months following baseline.
      RESULTS: Of the 2382 who met all eligibility criteria at the door, 1616 (67.8%)
      agreed to participate and were referred to the research center for further
      screening. The primary reason for ineligibility was inability to communicate in
      English. Results from the first 600 participants showed that participants are
      largely representative of seniors in the Boston area in terms of age, sex, race
      and Hispanic ethnicity. The average age of study participants was 77.9 years
      (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and
      17% black. Many participants (39%) reported having fallen at least once in the
      year before baseline. CONCLUSION: Our results demonstrate the feasibility of
      conducting comprehensive assessments, including rigorous physiologic
      measurements, in a diverse population of older adults to study non-traditional
      risk factors for falls and disability. The MBS will provide an important new data
      resource for examining novel risk factors for falls and mobility problems in the
      older population.

PMID- 18638391
TI  - AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for
      hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease.
AB  - BACKGROUND: The incidence and mortality of hepatocellular cancer (HCC)
      complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is
      rising in western societies. Despite knowing the at risk populations for HCC
      development, the lack of sensitive and specific means of surveillance hampers
      disease detection at curable stages. The most widely used serum HCC marker is
      alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell
      Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of
      these HCC biomarkers has largely been performed in patients with viral hepatitis.
      We conducted a cross sectional study assessing the value of these serum proteins,
      as well a novel candidate biomarker -follistatin - in patients with HCC arising
      on a background of ALD or NAFLD. METHODS: Pre-treatment serum samples from 50
      patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were
      assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin.
      Results were compared and contrasted with a control patient group with biopsy
      proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of
      each of the candidate biomarkers was evaluated using receiver operating
      characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and
      its 95% confidence interval (CI). Performance was compared to that of the
      established biomarker, AFP. RESULTS: Serum levels of all proteins were assessed
      by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance
      benefit in these patients. AFP and PIVKAII were superior to the other markers,
      particularly in combination. CONCLUSION: We conclude that while novel means of
      surveillance are urgently required, the combination of AFP and PIVKAII for HCC is
      an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this
      homogenous subset of patients- particularly that confirming no role for SCCA-1 -
      suggests that the choice of optimal biomarkers for HCC surveillance may be
      determined by the aetiology of underlying chronic liver disease.

PMID- 18638393
TI  - Successful management of Influenza A associated fulminant myocarditis: mobile
      circulatory support in intensive care unit: a case report.
AB  - A 26-year-old woman was referred to an Emergency Department because of common
      flu-like syndrome with hemodynamic collapse. In Intensive Care Unit (ICU), she
      was diagnosed as a probable septic shock. But despite treatment her condition
      rapidly deteriorated during the subsequent hours. Diagnosis of cardiogenic shock
      was established. Mechanical circulatory support was inserted into the patient.
      She was transferred in a Cardio-Vascular Surgical ICU where at the 5th day of
      mechanical circulatory support, echocardiography showed heart recovery which
      allowed weaning of mechanical circulatory support and progressive withdrawal of
      inotropic support. She was discharged at the 26th day. During her
      hospitalization, presence of Influenza A RNA was shown in myocardial biopsy.

PMID- 18638392
TI  - Viral hepatitis and HIV-associated tuberculosis: risk factors and TB treatment
      outcomes in Thailand.
AB  - BACKGROUND: The occurrence of tuberculosis (TB), human immunodeficiency virus
      (HIV), and viral hepatitis infections in the same patient poses unique clinical
      and public health challenges, because medications to treat TB and HIV are
      hepatotoxic. We conducted an observational study to evaluate risk factors for
      HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and
      TB treatment outcomes among HIV-infected TB patients. METHODS: Patients were
      evaluated at the beginning, during, and at the end of TB treatment. Blood samples
      were tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      total bilirubin (BR), complete blood count, and CD4+ T lymphocyte cell count. TB
      treatment outcomes were assessed at the end of TB treatment according to
      international guidelines. RESULTS: Of 769 enrolled patients, 752 (98%) had
      serologic testing performed for viral hepatitis: 70 (9%) were reactive for HBsAg,
      237 (31%) for anti-HCV, and 472 (63%) non-reactive for both markers. At the
      beginning of TB treatment, 18 (26%) patients with HBsAg reactivity had elevated
      liver function tests compared with 69 (15%) patients non-reactive to any viral
      marker (p = 0.02). At the end of TB treatment, 493 (64%) were successfully
      treated. Factors independently associated with HBsAg reactivity included being a
      man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval
      [CI], 1.1-4.3) and having low TB knowledge (AOR, 1.8; CI, 1.0-3.0). Factors most
      strongly associated with anti-HCV reactivity were having injection drug use
      history (AOR, 12.8; CI, 7.0-23.2) and living in Bangkok (AOR, 15.8; CI, 9.4
      26.5). The rate of clinical hepatitis and death during TB treatment was similar
      in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive,
      and non-reactive to any viral marker. CONCLUSION: Among HIV-infected TB patients
      living in Thailand, markers of viral hepatitis infection, particularly hepatitis
      C virus infection, were common and strongly associated with known behavioral risk
      factors. Viral hepatitis infection markers were not strongly associated with
      death or the development of clinical hepatitis during TB treatment.

PMID- 18638394
TI  - Three-dimensional transesophageal echocardiography of the atrial septal defects.
AB  - Transesophageal echocardiography has advantages over transthoracic technique in
      defining morphology of atrial structures. Even though real time three-dimensional
      echocardiographic imaging is a reality, the off-line reconstruction technique
      usually allows to obtain higher spatial resolution images. The purpose of this
      study was to explore the accuracy of off-line three-dimensional transesophageal
      echocardiography in a spectrum of atrial septal defects by comparing them with
      representative anatomic specimens.

PMID- 18638395
TI  - Factors associated with lack of postnatal care among Palestinian women: a cross
      sectional study of three clinics in the West Bank.
AB  - BACKGROUND: Only about one-third of women in Palestine (West Bank and Gaza)
      obtain postpartum care. Therefore, the goal of this study was to assess factors
      associated with lack of postnatal care, women's reasons for not obtaining
      postnatal care, and their attitudes towards its importance. METHODS: In early
      2006, a cross-sectional survey was conducted at three clinics run by the Ministry
      of Health providing Mother and Child Health Care in West Bank, Palestine. A total
      of 264 postpartum women attending the clinics were interviewed face-to-face,
      using a structured questionnaire. RESULTS: Although the majority of women
      considered postnatal care necessary (66.1%), only 36.6% of women obtained
      postnatal care. The most frequent reason for not obtaining postnatal care was
      that women did not feel sick and therefore did not need postnatal care (85%),
      followed by not having been told by their doctor to come back for postnatal care
      (15.5%). Based on a multivariable analysis, use of postnatal care was higher
      among women who had experienced problems during their delivery, had a cesarean
      section, or had an instrumental vaginal delivery than among women who had a
      spontaneous vaginal delivery. Use of postnatal care was also higher among women
      who delivered in a private hospital as compared to those who delivered in a
      public hospital. In addition, we found regional differences. CONCLUSION: The
      higher use of postnatal care among high-risk women is appropriate, but some
      clinically dangerous conditions can also occur in low-risk women. Future efforts
      should therefore focus on providing postnatal care to a larger number of low-risk
      women.

PMID- 18638396
TI  - SpliceCenter: a suite of web-based bioinformatic applications for evaluating the
      impact of alternative splicing on RT-PCR, RNAi, microarray, and peptide-based
      studies.
AB  - BACKGROUND: Over 60% of protein-coding genes in vertebrates express mRNAs that
      undergo alternative splicing. The resulting collection of transcript isoforms
      poses significant challenges for contemporary biological assays. For example, RT
      PCR validation of gene expression microarray results may be unsuccessful if the
      two technologies target different splice variants. Effective use of sequence
      based technologies requires knowledge of the specific splice variant(s) that are
      targeted. In addition, the critical roles of alternative splice forms in
      biological function and in disease suggest that assay results may be more
      informative if analyzed in the context of the targeted splice variant. RESULTS: A
      number of contemporary technologies are used for analyzing transcripts or
      proteins. To enable investigation of the impact of splice variation on the
      interpretation of data derived from those technologies, we have developed
      SpliceCenter. SpliceCenter is a suite of user-friendly, web-based applications
      that includes programs for analysis of RT-PCR primer/probe sets, effectors of
      RNAi, microarrays, and protein-targeting technologies. Both interactive and high
      throughput implementations of the tools are provided. The interactive versions of
      SpliceCenter tools provide visualizations of a gene's alternative transcripts and
      probe target positions, enabling the user to identify which splice variants are
      or are not targeted. The high-throughput batch versions accept user query files
      and provide results in tabular form. When, for example, we used SpliceCenter's
      batch siRNA-Check to process the Cancer Genome Anatomy Project's large-scale
      shRNA library, we found that only 59% of the 50,766 shRNAs in the library target
      all known splice variants of the target gene, 32% target some but not all, and 9%
      do not target any currently annotated transcript. CONCLUSION: SpliceCenter
      http://discover.nci.nih.gov/splicecenter provides unique, user-friendly
      applications for assessing the impact of transcript variation on the design and
      interpretation of RT-PCR, RNAi, gene expression microarrays, antibody-based
      detection, and mass spectrometry proteomics. The tools are intended for use by
      bench biologists as well as bioinformaticists.

PMID- 18638397
TI  - Impaired nuclear import and viral incorporation of Vpr derived from a HIV long
      term non-progressor.
AB  - We previously reported an epidemiologically linked HIV-1 infected patient cohort
      in which a long-term non-progressor (LTNP) infected two recipients who then
      exhibited normal disease progression. Expression of patient-derived vpr sequences
      from each of the three cohort members in mammalian cells tagged with GFP revealed
      a significant reduction in Vpr nuclear import and virion incorporation uniquely
      from the LTNP, whereas Vpr from the two progressing recipients displayed normal
      localisation and virion incorporation, implying a link between efficient Vpr
      nuclear import and HIV disease progression. Importantly, an F72L point mutation
      in the LTNP was identified for the first time as being uniquely responsible for
      decreased Vpr nuclear import.

PMID- 18638399
TI  - HIV transmission as a result of drug market violence: a case report.
AB  - While unprotected sexual intercourse and the use of contaminated injection
      equipment account for the majority of HIV infections worldwide, other routes of
      HIV transmission have received less attention. We report on a case of HIV
      transmission attributable to illicit drug market violence involving a participant
      in a prospective cohort study of injection drug users. Data from a qualitative
      interview was used in addition to questionnaire data and nursing records to
      document an episode of violence which likely resulted in this individual
      acquiring HIV infection. The case report demonstrates that the dangers of drug
      market violence go beyond the immediate physical trauma associated with violent
      altercations to include the possibility for infectious disease transmission. The
      case highlights the need to consider antiretroviral post-exposure prophylaxis in
      cases of drug market violence presenting to the emergency room, as well
      strategies to reduce violence associated with street-based drug markets.

PMID- 18638400
TI  - Intraoperative positioning related injury of superficial radial nerve after
      shoulder arthroscopy - a rare iatrogenic injury: a case report.
AB  - Arthroscopy of the shoulder is a well-established and routine procedure. The
      role is expected to increase further with an ever-increasing list of indications
      reflecting the gratifying results. Intraoperative injuries of nerves related to
      positioning are known but, fortunately, rare with shoulder arthroscopy.
      Appropriate assessment of patient and careful positioning is paramount in
      prevention of these injuries. Despite robust preventive measures, these injuries
      continue to occur from time to time. Although there are few reports of position
      related intraoperative nerve injuries associated with shoulder arthroscopy, the
      involvement of superficial radial nerve (SRN) has never been described before. We
      report a rare case of positioning related injury of SRN in a 35-year-old female
      after arthroscopic rotator cuff repair and discuss the preventive and legal
      aspects. To authors' knowledge this is the first reported case of intraoperative
      positioning related injury of SRN.

PMID- 18638398
TI  - Spatial variations in estimated chronic exposure to traffic-related air pollution
      in working populations: a simulation.
AB  - BACKGROUND: Chronic exposure to traffic-related air pollution is associated with
      a variety of health impacts in adults and recent studies show that exposure
      varies spatially, with some residents in a community more exposed than others. A
      spatial exposure simulation model (SESM) which incorporates six microenvironments
      (home indoor, work indoor, other indoor, outdoor, in-vehicle to work and in
      vehicle other) is described and used to explore spatial variability in estimates
      of exposure to traffic-related nitrogen dioxide (not including indoor sources)
      for working people. The study models spatial variability in estimated exposure
      aggregated at the census tracts level for 382 census tracts in the Greater
      Vancouver Regional District of British Columbia, Canada. Summary statistics
      relating to the distributions of the estimated exposures are compared visually
      through mapping. Observed variations are explored through analyses of model
      inputs. RESULTS: Two sources of spatial variability in exposure to traffic
      related nitrogen dioxide were identified. Median estimates of total exposure
      ranged from 8 microg/m3 to 35 microg/m3 of annual average hourly NO2 for workers
      in different census tracts in the study area. Exposure estimates are highest
      where ambient pollution levels are highest. This reflects the regional gradient
      of pollution in the study area and the relatively high percentage of time spent
      at home locations. However, for workers within the same census tract, variations
      were observed in the partial exposure estimates associated with time spent
      outside the residential census tract. Simulation modeling shows that some workers
      may have exposures 1.3 times higher than other workers residing in the same
      census tract because of time spent away from the residential census tract, and
      that time spent in work census tracts contributes most to the differences in
      exposure. Exposure estimates associated with the activity of commuting by vehicle
      to work were negligible, based on the relatively short amount of time spent in
      this microenvironment compared to other locations. We recognize that this may not
      be the case for pollutants other than NO2. These results represent the first time
      spatially disaggregated variations in exposure to traffic-related air pollution
      within a community have been estimated and reported. CONCLUSION: The results
      suggest that while time spent in the home indoor microenvironment contributes
      most to between-census tract variation in estimates of annual average exposures
      to traffic-related NO2, time spent in the work indoor microenvironment
      contributes most to within-census tract variation, and time spent in transit by
      vehicle makes a negligible contribution. The SESM has potential as a policy
      evaluation tool, given input data that reflect changes in pollution levels or
      work flow patterns due to traffic demand management and land use development
      policy.

PMID- 18638402
TI  - Paraganglioma-like dermal melanocytic tumor: a case report.
AB  - Paraganglioma-like dermal melanocytic tumor is a rare subtype of benign dermal
      melanocytic tumors. Its histopathologic features resemble those of paraganglioma,
      but the immunostaining characteristics are those of melanocytic lesions.We report
      a case of a 60-year-old male with a paraganglioma-like dermal melanocytic tumor
      of his left cheek and briefly review the English literature.

PMID- 18638401
TI  - Improving inter-observer variability in the evaluation of ultrasonographic
      features of polycystic ovaries.
AB  - BACKGROUND: We recently reported poor inter-observer agreement in identifying and
      quantifying individual ultrasonographic features of polycystic ovaries. Our
      objective was to determine the effect of a training workshop on reducing inter
      observer variation in the ultrasonographic evaluation of polycystic ovaries.
      METHODS: Transvaginal ultrasound recordings from thirty women with polycystic
      ovary syndrome (PCOS) were evaluated by three radiologists and three reproductive
      endocrinologists both before and after an ultrasound workshop. The following
      endpoints were assessed: 1) follicle number per ovary (FNPO), 2) follicle number
      per single cross-section (FNPS), 3) largest follicle diameter, 4) ovarian volume,
      5) follicle distribution pattern and 6) presence of a corpus luteum (CL). Lin's
      concordance correlation coefficients (rho) and kappa statistics for multiple
      raters (kappa) were used to assess level of inter-observer agreement (>0.80 good,
      0.60 - 0.80 moderate/fair, <0.60 poor). RESULTS: Following the workshop, inter
      observer agreement improved for the evaluation of FNPS (rho = 0.70, delta rho =
      +0.11), largest follicle diameter (rho = 0.77, delta rho = +0.10), ovarian volume
      (rho = 0.84, delta rho = +0.12), follicle distribution pattern (kappa = 0.80,
      delta kappa = +0.21) and presence of a CL (kappa = 0.87, delta kappa = +0.05). No
      improvement was evident for FNPO (rho = 0.54, delta rho = -0.01). Both
      radiologists and reproductive endocrinologists demonstrated improvement in scores
      (p < 0.001). CONCLUSION: Reliability in evaluating ultrasonographic features of
      polycystic ovaries can be significantly improved following participation in a
      training workshop. If ultrasonographic evidence of polycystic ovaries is to be
      used as an objective measure in the diagnosis of PCOS, then standardized training
      modules should be implemented to unify the approach to evaluating polycystic
      ovarian morphology.

PMID- 18638403
TI  - Unexpected limited chronic dissection of the ascending aorta.
AB  - We report a rare case of a limited chronic dissection of the ascending aorta that
      was accidentally discovered at operation performed for severe aortic stenosis and
      moderate to severe dilatation of the ascending aorta. Preoperative investigations
      such as transoesophageal echocardiography and cardiac catheterization missed the
      diagnosis of dissection. Intraoperative findings included a 3.5 cm eccentric
      bulge of the ascending aorta and a 5 mm circular shaped intimal tear comunicating
      with a limited hematoma or small dissection of the media layer. (The rarety of
      the report is that the chronic dissection is limited to a small area
      (approximatively 3.5 x 2.5 cm) of the ascending aorta).

PMID- 18638404
TI  - Adrenalectomy for solitary adrenal metastasis from colorectal cancer: A case
      report.
AB  - BACKGROUND: Patients with adrenal metastasis from various primary tumours are
      regarded as cases of diffuse systemic spread and considered unsuitable for
      surgical resection. We herein report an operable case of heterochronic adrenal
      metastasis from colorectal carcinoma in a 63-year-old woman. CASE PRESENTATION:
      Sixteen months after low anterior resection for the primary tumour, left lower
      pneumonectomy was performed for a solitary lung metastasis. Four months later a
      right adrenal metastasis was detected by magnetic resonance imaging (MRI), as
      sole evidence of metastatic disease. A right adrenalectomy was performed. The
      histopathological examination revealed adenocarcinoma compatible with the
      colorectal carcinoma resected 19 months earlier. The patient received adjuvant
      chemotherapy after each operation and is alive and free of disease 21 months
      after the adrenalectomy. CONCLUSION: The possibility of adrenal metastasis should
      be considered in the follow-up of patients after primary surgery for colorectal
      cancer, even though other sites are the main metastatic sites. Although the
      prognosis of adrenal metastasis from colorectal cancer is poor, we suggest that
      patients with solitary adrenal metastasis may benefit from complete removal of
      it.

PMID- 18638406
TI  - Giant tonsillolith causing odynophagia in a child: a rare case report.
AB  - Giant tonsillolith is a rare clinical entity. Commonly, it occurs between 20-77
      years of age. We had a twelve years old female patient, who had odynophagia due
      to a giant tonsillolith. The stone was removed and tonsillectomy was performed.
      We reviewed the literature on this rare clinical entity and found that this is
      the fourth case of giant tonsillolith in a child and largest ever tonsillolith to
      be reported in English literature.

PMID- 18638405
TI  - The impact of generic-only drug benefits on patients' use of inhaled
      corticosteroids in a Medicare population with asthma.
AB  - BACKGROUND: Patients face increasing insurance restrictions on prescription
      drugs, including generic-only coverage. There are no generic inhaled
      corticosteroids (ICS), which are a mainstay of asthma therapy, and patients pay
      the full price for these drugs under generic-only policies. We examined changes
      in ICS use following the introduction of generic-only coverage in a Medicare
      Advantage population from 2003-2004. METHODS: Subjects were age 65+, with asthma,
      prior ICS use, and no chronic obstructive pulmonary disorder (n = 1,802). In
      2004, 74.0% switched from having a $30 brand-copayment plan to a generic-only
      coverage plan (restricted coverage); 26% had $15-25 brand copayments in 2003-2004
      (unrestricted coverage). Using linear difference-in-difference models, we
      examined annual changes in ICS use (measured by days-of-supply dispensed). There
      was a lower-cost ICS available within the study setting and we also examined
      changes in drug choice (higher- vs. lower-cost ICS). In multivariable models we
      adjusted for socio-demographic, clinical, and asthma characteristics. RESULTS: In
      2003 subjects had an average of 188 days of ICS supply. Restricted compared with
      unrestricted coverage was associated with reductions in ICS use from 2003-2004 (
      15.5 days-of-supply, 95% confidence interval (CI): -25.0 to -6.0). Among patients
      using higher-cost ICS drugs in 2003 (n = 662), more restricted versus
      unrestricted coverage subjects switched to the lower-cost ICS in 2004 (39.8% vs.
      10.3%). Restricted coverage was not associated with decreased ICS use (2003-2004)
      among patients who switched to the lower-cost ICS (18.7 days-of-supply, CI: -27.5
      to 65.0), but was among patients who did not switch (-38.6 days-of-supply, CI: 
      57.0 to -20.3). In addition, restricted coverage was associated with decreases in
      ICS use among patients with both higher- and lower-risk asthma (-15.0 days-of
      supply, CI: -41.4 to 11.44; and -15.6 days-of-supply, CI: -25.8 to -5.3,
      respectively). CONCLUSION: In this elderly population, patients reduced their
      already low ICS use in response to losing drug coverage. Switching to the lower
      cost ICS mitigated reductions in use among patients who previously used higher
      cost drugs. Additional work is needed to assess barriers to switching ICS drugs
      and the clinical effects of these drug use changes.

PMID- 18638407
TI  - Parasitization by the wasp Eretmocerus mundus induces transcription of genes
      related to immune response and symbiotic bacteria proliferation in the whitefly
      Bemisia tabaci.
AB  - BACKGROUND: The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), and
      the viruses it transmits, are a major constraint to growing vegetable crops
      worldwide. Although the whitefly is often controlled using chemical pesticides,
      biological control agents constitute an important component in integrated pest
      management programs, especially in protected agriculture. One of these agents is
      the wasp Eretmocerus mundus (Mercet) (Hymenoptera: Aphelinidae). E. mundus lays
      its egg on the leaf underneath the second-third instar nymph of B. tabaci. First
      instars of the wasp hatch and penetrate the whitefly nymphs. Initiation of
      parasitization induces the host to form a capsule composed of epidermal cells
      around the parasitoid. The physiological and molecular processes underlying B.
      tabaci-E. mundus interactions have never been investigated. RESULTS: We used a
      cDNA microarray containing 6,000 expressed sequence tags (ESTs) from the whitefly
      genome to study the parasitoid-whitefly interaction. We compared RNA samples
      collected at two time points of the parasitization process: when the parasitoid
      first instar starts the penetration process and once it has fully penetrated the
      host. The results clearly indicated that genes known to be part of the defense
      pathways described in other insects are also involved in the response of B.
      tabaci to parasitization by E. mundus. Some of these responses included
      repression of a serine protease inhibitor (serpin) and induction of a
      melanization cascade. A second set of genes that responded strongly to
      parasitization were bacterial, encoded by whitefly symbionts. Quantitative real
      time PCR and FISH analyses showed that proliferation of Rickettsia, a facultative
      secondary symbiont, is strongly induced upon initiation of the parasitization
      process, a result that supported previous reports suggesting that endosymbionts
      might be involved in the insect host's resistance to various environmental
      stresses. CONCLUSION: This is the first study to examine the transcriptional
      response of a hemipteran insect to attack by a biological control agent
      (hymenopterous parasitoid), using a new genomic approach developed for this
      insect pest. The defense response in B. tabaci involves genes related to the
      immune response as described in model organisms such as Drosophila melanogaster.
      Moreover, endosymbionts of B. tabaci appear to play a role in the response to
      parasitization, as supported by previously published results from aphids.

PMID- 18638408
TI  - Enzymatic, immunological and phylogenetic characterization of Brucella suis
      urease.
AB  - BACKGROUND: The sequenced genomes of the Brucella spp. have two urease operons,
      ure-1 and ure-2, but there is evidence that only one is responsible for encoding
      an active urease. The present work describes the purification and the enzymatic
      and phylogenomic characterization of urease from Brucella suis strain 1330.
      Additionally, the urease reactivity of sera from patients diagnosed with
      brucellosis was examined. RESULTS: Urease encoded by the ure-1 operon of Brucella
      suis strain 1330 was purified to homogeneity using ion exchange and hydrophobic
      interaction chromatographies. The urease was purified 51-fold with a recovery of
      12% of the enzyme activity and 0.24% of the total protein. The enzyme had an
      isoelectric point of 5, and showed optimal activity at pH 7.0 and 28-35 degrees
      C. The purified enzyme exhibited a Michaelis-Menten saturation kinetics with a Km
      of 5.60 +/- 0.69 mM. Hydroxyurea and thiourea are competitive inhibitors of the
      enzyme with Ki of 1.04 +/- 0.31 mM and 26.12 +/- 2.30 mM, respectively.
      Acetohydroxamic acid also inhibits the enzyme in a competitive way. The molecular
      weight estimated for the native enzyme was between 130-135 kDa by gel filtration
      chromatography and 157 +/- 7 kDa using 5-10% polyacrylamide gradient non
      denaturing gel. Only three subunits in SDS-PAGE were identified: two small
      subunits of 14,000 Da and 15,500 Da, and a major subunit of 66,000 Da. The amino
      terminal sequence of the purified large subunit corresponded to the predicted
      amino acid sequence encoded by ureC1. The UreC1 subunit was recognized by sera
      from patients with acute and chronic brucellosis. By phylogenetic and cluster
      structure analyses, ureC1 was related to the ureC typically present in the
      Rhizobiales; in contrast, the ureC2 encoded in the ure-2 operon is more related
      to distant species. CONCLUSION: We have for the first time purified and
      characterized an active urease from B. suis. The enzyme was characterized at the
      kinetic, immunological and phylogenetic levels. Our results confirm that the
      active urease of B. suis is a product of ure-1 operon.

PMID- 18638409
TI  - The cost of wobble translation in fungal mitochondrial genomes: integration of
      two traditional hypotheses.
AB  - BACKGROUND: Fungal and animal mitochondrial genomes typically have one tRNA for
      each synonymous codon family. The codon-anticodon adaptation hypothesis predicts
      that the wobble nucleotide of a tRNA anticodon should evolve towards maximizing
      Watson-Crick base pairing with the most frequently used codon within each
      synonymous codon family, whereas the wobble versatility hypothesis argues that
      the nucleotide at the wobble site should be occupied by a nucleotide most
      versatile in wobble pairing, i.e., the tRNA wobble nucleotide should be G for NNY
      codon families, and U for NNR and NNN codon families (where Y stands for C or U,
      R for A or G and N for any nucleotide). RESULTS: We here integrate these two
      traditional hypotheses on tRNA anticodons into a unified model based on an
      analysis of the wobble costs associated with different wobble base pairs. This
      novel approach allows the relative cost of wobble pairing to be qualitatively
      evaluated. A comprehensive study of 36 fungal genomes suggests very different
      costs between two kinds of U:G wobble pairs, i.e., (1) between a G at the wobble
      site of a tRNA anticodon and a U at the third codon position (designated MU3:G)
      and (2) between a U at the wobble site of a tRNA anticodon and a G at the third
      codon position (designated MG3:U). CONCLUSION: In general, MU3:G is much smaller
      than MG3:U, suggesting no selection against U-ending codons in NNY codon families
      with a wobble G in the tRNA anticodon but strong selection against G-ending
      codons in NNR codon families with a wobble U at the tRNA anticodon. This finding
      resolves several puzzling observations in fungal genomics and corroborates
      previous studies showing that U3:G wobble is energetically more favorable than
      G3:U wobble.

PMID- 18638410
TI  - Osteopathy may decrease obstructive apnea in infants: a pilot study.
AB  - BACKGROUND: Obstructive apnea is a sleep disorder characterized by pauses in
      breathing during sleep: breathing is interrupted by a physical block to airflow
      despite effort. The purpose of this study was to test if osteopathy could
      influence the incidence of obstructive apnea during sleep in infants. METHODS:
      Thirty-four healthy infants (age: 1.5-4.0 months) were recruited and randomized
      in two groups; six infants dropped out. The osteopathy treatment group (n = 15
      infants) received 2 osteopathic treatments in a period of 2 weeks and a control
      group (n = 13 infants) received 2 non-specific treatments in the same period of
      time. The main outcome measure was the change in the number of obstructive apneas
      measured during an 8-hour polysomnographic recording before and after the two
      treatment sessions. RESULTS: The results of the second polysomnographic
      recordings showed a significant decrease in the number of obstructive apneas in
      the osteopathy group (p = 0.01, Wilcoxon test), in comparison to the control
      group showing only a trend suggesting a gradual physiologic decrease of
      obstructive apneas. However, the difference in the decline of obstructive apneas
      between the groups after treatment was not significant (p = 0.43). CONCLUSION:
      Osteopathy may have a positive influence on the incidence of obstructive apneas
      during sleep in infants with a previous history of obstructive apneas as measured
      by polysomnography. Additional research in this area appears warranted.

PMID- 18638411
TI  - A new perspective on phylogeny and evolution of tetraodontiform fishes (Pisces:
      Acanthopterygii) based on whole mitochondrial genome sequences: basal ecological
      diversification?
AB  - BACKGROUND: The order Tetraodontiformes consists of approximately 429 species of
      fishes in nine families. Members of the order exhibit striking morphological
      diversity and radiated into various habitats such as freshwater, brackish and
      coastal waters, open seas, and deep waters along continental shelves and slopes.
      Despite extensive studies based on both morphology and molecules, there has been
      no clear resolution except for monophyly of each family and sister-group
      relationships of Diodontidae + Tetraodontidae and Balistidae + Monacanthidae. To
      address phylogenetic questions of tetraodontiform fishes, we used whole
      mitochondrial genome (mitogenome) sequences from 27 selected species (data for 11
      species were newly determined during this study) that fully represent all
      families and subfamilies of Tetraodontiformes (except for Hollardinae of the
      Triacanthodidae). Partitioned maximum likelihood (ML) and Bayesian analyses were
      performed on two data sets comprising concatenated nucleotide sequences from 13
      protein-coding genes (all positions included; third codon positions converted
      into purine [R] and pyrimidine [Y]), 22 transfer RNA and two ribosomal RNA genes
      (total positions = 15,084). RESULTS: The resultant tree topologies from the two
      data sets were congruent, with many internal branches showing high support
      values. The mitogenomic data strongly supported monophyly of all families and
      subfamilies (except the Tetraodontinae) and sister-group relationships of
      Balistidae + Monacanthidae and Tetraodontidae + Diodontidae, confirming the
      results of previous studies. However, we also found two unexpected basal splits
      into Tetraodontoidei (Triacanthidae + Balistidae + Monacanthidae + Tetraodontidae
      + Diodontidae + Molidae) and Triacanthodoidei (Ostraciidae + Triodontidae +
      Triacanthodidae). CONCLUSION: This basal split into the two clades has never been
      reported and challenges previously proposed hypotheses based on both morphology
      and nuclear gene sequences. It is likely that the basal split had involved
      ecological diversification, because most members of Tetraodontoidei exclusively
      occur in shallow waters (freshwater, brackish and coastal waters, and open seas),
      while those of Triacanthodoidei occur mainly in relatively deep waters along
      continental shelves and slopes except for more derived ostraciids. This suggests
      that the basal split between the two clades led to subsequent radiation into the
      two different habitats.

PMID- 18638412
TI  - Collaborative review of pilot projects to inform policy: A methodological remedy
      for pilotitis?
AB  - BACKGROUND: In rural health and other health service development contexts, there
      is frustration with a reliance on pilot projects as a means of informing policy
      and service innovation. There is also an emerging recognition that existing
      research methods do not draw lessons from the failed sustainability that
      characterises many of these pilots and demonstration projects. DISCUSSION: This
      article describes critical aspects of the methodology of a successful
      collaborative, multi-method, systematic synthesis of exemplary primary health
      care pilot projects in rural and remote Australia, which synthesised principles
      from a number of pilot projects to inform policy makers and planners. Hallmarks
      of the method were: the nature of the source materials for the research, the
      subsequent research engagement with the actual pilot projects, the extent of
      collaboration throughout the study with end-users from policy and planning
      arenas, and the attention to procedural quality. SUMMARY: The methodology, while
      time consuming, has resulted in applied, policy-relevant findings, and evidence
      of consideration by policy-makers.

PMID- 18638413
TI  - A scoping review of research on complementary and alternative medicine (CAM) and
      the mass media: looking back, moving forward.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) has become
      more common in Western developed countries in recent years, as has media
      reporting on CAM and related issues. Correspondingly, media reports are a primary
      information source regarding decisions to use CAM. Research on CAM related media
      reports is becoming increasingly relevant and important; however, identifying key
      concepts to guide future research is problematic due to the dispersed nature of
      completed research in this field. A scoping review was conducted to: 1) determine
      the amount, focus and nature of research on CAM and the mass media; and 2)
      summarize and disseminate related research results. METHODS: The main phases
      were: 1) searching for relevant studies; 2) selecting studies based on pre
      defined inclusion criteria; 3) extracting data; and 4) collating, summarizing and
      reporting the results. RESULTS: Of 4,454 studies identified through various
      search strategies, 16 were relevant to our objectives and included in a final
      sample. CAM and media research has focused primarily on print media coverage of a
      range of CAM therapies, although only a few studies articulated differences
      within the range of therapies surveyed. Research has been developed through a
      variety of disciplinary perspectives, with a focus on representation research.
      The research reviewed suggests that journalists draw on a range of sources to
      prepare media reports, although most commonly they cite conventional (versus CAM)
      sources and personal anecdotes. The tone of media reports appears generally
      positive, which may be related to a lack of reporting on issues related to risk
      and safety. Finally, a variety of discourses within media representations of CAM
      are apparent that each appeal to a specific audience through resonance with their
      specific concerns. CONCLUSION: Research on CAM and the mass media spans multiple
      disciplines and strategies of inquiry; however, despite the diversity in
      approach, it is clear that issues related to production and reception of media
      content are in need of research attention. To address the varied issues in a
      comprehensive manner, future research needs to be collaborative, involving
      researchers across disciplines, journalists and CAM users.

PMID- 18638415
TI  - Atrial septal aneurysm associated with additional cardiovascular comorbidities in
      two middle age female patients with ECG signs of right bundle branch block: two
      case reports.
AB  - INTRODUCTION: Atrial septal aneurysm (ASA) is often associated with other atrial
      septal abnormalities, particularly with atrial septal defect type ostium secundum
      or patent foramen ovale. ECG signs of incomplete or complete right bundle branch
      block are known to be associated with atrial septal defects, however such
      correlation with other atrial septal abnormalities is not documented. CASE
      PRESENTATIONS: We report here two cases of middle age female patients that
      presented with dyspnea on physical effort, right bundle branch block (RBBB) on
      ECG and ASA combined with other cardiac disorders. Transesophageal
      echocardiography revealed additional information to the ones obtained by surface
      echocardiography, in both cases. CONCLUSION: ASA associated with RBBB on ECG may
      serve as a hint for the presence of additional cardiac abnormalities, thus
      rousing the demand for a detailed cardiac investigation.

PMID- 18638414
TI  - Successful elimination of non-neural cells and unachievable elimination of glial
      cells by means of commonly used cell culture manipulations during differentiation
      of GFAP and SOX2 positive neural progenitors (NHA) to neuronal cells.
AB  - BACKGROUND: Although extensive research has been performed to control
      differentiation of neural stem cells - still, the response of those cells to
      diverse cell culture conditions often appears to be random and difficult to
      predict. To this end, we strived to obtain stabilized protocol of NHA cells
      differentiation - allowing for an increase in percentage yield of neuronal cells.
      RESULTS: Uncommitted GFAP and SOX2 positive neural progenitors - so-called,
      Normal Human Astrocytes (NHA) were differentiated in different environmental
      conditions to: only neural cells consisted of neuronal [MAP2+, GFAP-] and glial
      [GFAP+, MAP2-] population, non-neural cells [CD44+, VIMENTIN+, FIBRONECTIN+, MAP2
      , GFAP-, S100beta-, SOX2-], or mixture of neural and non-neural cells.In spite of
      successfully increasing the percentage yield of glial and neuronal vs. non-neural
      cells by means of environmental changes, we were not able to increase
      significantly the percentage of neuronal (GABA-ergic and catecholaminergic) over
      glial cells under several different cell culture testing conditions.
      Supplementing serum-free medium with several growth factors (SHH, bFGF, GDNF) did
      not radically change the ratio between neuronal and glial cells--i.e., 1,1:1 in
      medium without growth factors and 1,4:1 in medium with GDNF, respectively.
      CONCLUSION: We suggest that biotechnologists attempting to enrich in vitro neural
      cell cultures in one type of cells - such as that required for transplantology
      purposes, should consider the strong limiting influence of intrinsic factors upon
      extracellular factors commonly tested in cell culture conditions.

PMID- 18638416
TI  - Assessing probe-specific dye and slide biases in two-color microarray data.
AB  - BACKGROUND: A primary reason for using two-color microarrays is that the use of
      two samples labeled with different dyes on the same slide, that bind to probes on
      the same spot, is supposed to adjust for many factors that introduce noise and
      errors into the analysis. Most users assume that any differences between the dyes
      can be adjusted out by standard methods of normalization, so that measures such
      as log ratios on the same slide are reliable measures of comparative expression.
      However, even after the normalization, there are still probe specific dye and
      slide variation among the data. We define a method to quantify the amount of the
      dye-by-probe and slide-by-probe interaction. This serves as a diagnostic, both
      visual and numeric, of the existence of probe-specific dye bias. We show how this
      improved the performance of two-color array analysis for arrays for genomic
      analysis of biological samples ranging from rice to human tissue. RESULTS: We
      develop a procedure for quantifying the extent of probe-specific dye and slide
      bias in two-color microarrays. The primary output is a graphical diagnostic of
      the extent of the bias which called ECDF (Empirical Cumulative Distribution
      Function), though numerical results are also obtained. CONCLUSION: We show that
      the dye and slide biases were high for human and rice genomic arrays in two gene
      expression facilities, even after the standard intensity-based normalization, and
      describe how this diagnostic allowed the problems causing the probe-specific bias
      to be addressed, and resulted in important improvements in performance. The R
      package LMGene which contains the method described in this paper has been
      available to download from Bioconductor.

PMID- 18638417
TI  - Structural analysis of urate oxidase in complex with its natural substrate
      inhibited by cyanide: mechanistic implications.
AB  - BACKGROUND: Urate oxidase (EC 1.7.3.3 or UOX) catalyzes the conversion of uric
      acid and gaseous molecular oxygen to 5-hydroxyisourate and hydrogen peroxide, in
      the absence of cofactor or particular metal cation. The functional enzyme is a
      homo-tetramer with four active sites located at dimeric interfaces. RESULTS: The
      catalytic mechanism was investigated through a ternary complex formed between the
      enzyme, uric acid, and cyanide that stabilizes an intermediate state of the
      reaction. When uric acid is replaced by a competitive inhibitor, no complex with
      cyanide is formed. CONCLUSION: The X-ray structure of this compulsory ternary
      complex led to a number of mechanistic evidences that support a sequential
      mechanism in which the two reagents, dioxygen and a water molecule, process
      through a common site located 3.3 A above the mean plane of the ligand. This site
      is built by the side chains of Asn 254, and Thr 57, two conserved residues
      belonging to two different subunits of the homo-tetramer. The absence of a
      ternary complex between the enzyme, a competitive inhibitor, and cyanide suggests
      that cyanide inhibits the hydroxylation step of the reaction, after the initial
      formation of a hydroperoxyde type intermediate.

PMID- 18638418
TI  - Blocking primers to enhance PCR amplification of rare sequences in mixed samples 
      a case study on prey DNA in Antarctic krill stomachs.
AB  - BACKGROUND: Identification of DNA sequence diversity is a powerful means for
      assessing the species present in environmental samples. The most common molecular
      strategies for estimating taxonomic composition depend upon PCR with universal
      primers that amplify an orthologous DNA region from a range of species. The
      diversity of sequences within a sample that can be detected by universal primers
      is often compromised by high concentrations of some DNA templates. If the DNA
      within the sample contains a small number of sequences in relatively high
      concentrations, then less concentrated sequences are often not amplified because
      the PCR favours the dominant DNA types. This is a particular problem in molecular
      diet studies, where predator DNA is often present in great excess of food-derived
      DNA. RESULTS: We have developed a strategy where a universal PCR simultaneously
      amplifies DNA from food items present in DNA purified from stomach samples, while
      the predator's own DNA is blocked from amplification by the addition of a
      modified predator-specific blocking primer. Three different types of modified
      primers were tested out; one annealing inhibiting primer overlapping with the 3'
      end of one of the universal primers, another annealing inhibiting primer also
      having an internal modification of five dI molecules making it a dual priming
      oligo, and a third elongation arrest primer located between the two universal
      primers. All blocking primers were modified with a C3 spacer. In artificial PCR
      mixtures, annealing inhibiting primers proved to be the most efficient ones and
      this method reduced predator amplicons to undetectable levels even when predator
      template was present in 1000 fold excess of the prey template. The prey template
      then showed strong PCR amplification where none was detectable without the
      addition of blocking primer. Our method was applied to identifying the winter
      food of one of the most abundant animals in the world, the Antarctic krill,
      Euphausia superba. Dietary item DNA was PCR amplified from a range of species in
      krill stomachs for which we had no prior sequence knowledge. CONCLUSION: We
      present a simple, robust and cheap method that is easily adaptable to many
      situations where a rare DNA template is to be PCR amplified in the presence of a
      higher concentration template with identical PCR primer binding sites.

PMID- 18638419
TI  - Health-related quality of life among general practice patients with differing
      chronic diseases in Germany: cross sectional survey.
AB  - BACKGROUND: This study was carried out to compare the HRQoL of patients in
      general practice with differing chronic diseases with the HRQoL of patients
      without chronic conditions, to evaluate the HRQoL of general practice patients in
      Germany compared with the HRQoL of the general population, and to explore the
      influence of different chronic diseases on patients' HRQoL, independently of the
      effects of multiple confounding variables. METHODS: A cross-sectional
      questionnaire survey including the SF-36, the EQ-5D and demographic questions was
      conducted in 20 general practices in Germany. 1009 consecutive patients aged 15
      89 participated. The SF-36 scale scores of general practice patients with
      differing chronic diseases were compared with those of patients without chronic
      conditions. Differences in the SF-36 scale/summary scores and proportions in the
      EQ-5D dimensions between patients and the general population were analyzed.
      Independent effects of chronic conditions and demographic variables on the HRQoL
      were analyzed using multivariable linear regression and polynomial regression
      models. RESULTS: The HRQoL for general practice patients with differing chronic
      diseases tended to show more physical than mental health impairments compared
      with the reference group of patients without. Patients in general practice in
      Germany had considerably lower SF-36 scores than the general population (P <
      0.001 for all) and showed significantly higher proportions of problems in all EQ
      5D dimensions except for the self-care dimension (P < 0.001 for all). The mean EQ
      VAS for general practice patients was lower than that for the general population
      (69.2 versus 77.4, P < 0.001). The HRQoL for general practice patients in Germany
      seemed to be more strongly affected by diseases like depression, back pain, OA of
      the knee, and cancer than by hypertension and diabetes. CONCLUSION: General
      practice patients with differing chronic diseases in Germany had impaired quality
      of life, especially in terms of physical health. The independent impacts on the
      HRQoL were different depending on the type of chronic disease. Findings from this
      study might help health professionals to concern more influential diseases in
      primary care from the patient's perspective.

PMID- 18638420
TI  - Temporary ectropion therapy by adhesive taping: a case study.
AB  - INTRODUCTION: Various surgical procedures are available to correct paralytic
      ectropion, which are applied in irreversible facial paresis. Problems occur when
      facial paresis has an unclear prognosis, since surgery of the lower eyelid is
      usually irreversible. We propose a simple method to correct temporary ectropion
      in facial palsy by applying an adhesive strip. PATIENTS AND METHODS: Ten patients
      with peripheral facial paresis and paralytic ectropion were treated with an
      adhesive strip to correct paralytic ectropion. We used "Steri-Strips" (45 x 6.0
      mm), which were taped on the carefully cleaned skin of the lower eyelid and of
      the adjacent zygomatic region until the prognosis of the paresis was clarified.
      In addition to the examiner's evaluation of the lower lacrimal point in the
      lacrimal lake, subjective improvement of the symptoms was assessed using a visual
      analogue scale (VAS, 1-10). RESULTS: 9 patients reported a clear improvement of
      the symptoms after adhesive taping. There was a clear regression of tearing (VAS
      (median) = 8; 1 = no improvement, 10 = very good improvement), the cosmetic
      impairment of the adhesive tape was low (VAS (median) = 2.5; 1 = no impairment,
      10 = severe impairment) and most of the patients found the use of the adhesive
      strip helpful. There was slight reddening of the skin in one case and well
      tolerated by the facial skin in the other cases. CONCLUSION: The cause and
      location of facial nerve damage are decisive for the type of surgical therapy. In
      potentially reversible facial paresis, procedures should be used that are easily
      performed and above all reversible without complications. Until a reliable
      prognosis of the paresis can be made, adhesive taping is suited for the temporary
      treatment of paralytic ectropion. Adhesive taping is simple and can be performed
      by the patient.

PMID- 18638421
TI  - Lessons learned from a series of patients with missed aortopulmonary windows.
AB  - OBJECTIVES: To identify factors contributing to missed diagnosis of
      aortopulmonary windows on initial echocardiographic examination; and to analyze
      lesions associated with these malformations. DESIGN: Retrospective study where
      echocardiographic findings and per-operative findings of patients were correlated
      by reviewing records. SETTING: Tertiary-care paediatric cardiac centre. PATIENTS:
      From May 2002 to September 2007, we diagnosed 50 patients with aortopulmonary
      windows. The group included 31 boys and 19 girls. Mean age at intervention was
      1.7 years, with a range from 3 months to 17 years. RESULTS: The diagnosis of
      aortopulmonary window was made correctly by echocardiography during initial
      evaluation in 46 of 50 patients (92%). The remaining 4 patients were diagnosed
      either during repeat echocardiographic evaluation, cardiac catheterization, or
      per-operatively. We describe the details of these patients. Of the 50 patients,
      23 had associated malformations, including ventricular septal defects in 10
      patients, patent arterial ducts in 9, atrial septal defects or patent oval
      foramens in 5, 3 of whom also had patent arterial ducts, interruption of the
      aortic arch at the isthmus in 4, or between the left subclavian and common
      carotid arteries in 2, tetralogy of Fallot in 2, double-outlet right ventricle in
      2, discordant ventriculo-arterial connections in 2, 1 of whom also had anomalous
      origin of the left coronary artery from the pulmonary trunk, and superior
      inferior ventricles in 1 patient. CONCLUSIONS: Even meticulous echocardiography
      may result in a false negative diagnosis of an aortopulmonary window. A high
      index of suspicion for this lesion is warranted in cases of unexplained severe
      pulmonary arterial hypertension, and/or unexplained cardiac dilation.

PMID- 18638422
TI  - The activity of the Na+/Ca2+ exchanger largely modulates the Ca2+i signal induced
      by hypo-osmotic stress in rat cerebellar astrocytes. The effect of osmolarity on
      exchange activity.
AB  - We recently demonstrated that rat cerebellar Type-1 astrocytes express a very
      active Na(+)/Ca(2+) exchanger highly colocalized with ryanodine receptors (RyRs),
      which in turn play a key role in glutamate-induced Ca(2+) signaling through a
      calcium-induced calcium release (CICR) mechanism. In this work we have explored
      whether the Na(+)/Ca(2+) exchanger has any role in the Ca(2+)(i) signal induced
      by hypo-osmotic stress in these cells, using microspectrofluorometric
      measurements with Fura-2, pharmacological tools, and confocal microscopy image
      analysis. We present evidence for the first time that the increase in [Ca(2+)](i)
      in rat cerebellar Type-1 astrocytes, resulting from moderate hypotonic shock, is
      mediated by Ca(2+) release from ryanodine-operated Ca(2+)(i) stores, and that the
      magnitude of the intracellular Ca(2+) signal induced by hypotonicity in the short
      term (up to 240 s) is small and controlled by the activity of the Na(+)/Ca(2+)
      exchanger operating in its extrusion mode. With longer times in the hypotonic
      medium, intracellular Ca(2+) store depletion leads to Ca(2+) entry through store
      operated Ca(2+) channels. We found it interesting that the activity of the
      Na(+)/Ca(2+) exchanger measured during this reverse mode operation (Ca(2+) entry
      in exchange for internal Na(+)) was found to be greatly increased in hypotonic
      solutions and decreased in hypertonic ones. The buffering of the [Ca(2+)](i) rise
      induced by hypo-osmotic stress may prevent excessive increases in [Ca(2+)](i),
      which otherwise might impair the normal function of this glial cell.

PMID- 18638423
TI  - Anticyclic citrullinated peptide antibody-negative rheumatoid arthritis: clues to
      disease pathogenesis.

PMID- 18638424
TI  - In perspective: murine models of scleroderma.
AB  - An understanding of the complex pathogenesis of systemic sclerosis (SSc) has been
      slow to emerge, due in large part to the lack of an animal model recapitulating
      the three cardinal attributes of SSc: autoimmunity, vasculopathy, and fibrosis.
      Experimental manipulations in inbred murine strains can lead to conditions that
      mimic SSc fibrosis. Furthermore, genetic engineering has enabled the creation of
      novel murine strains that spontaneously develop fibrosis or are protected from
      fibrosis development. Studies of these mice shed light on the cell types, cell
      interactions, molecules, and pathways that contribute to SSc manifestations. High
      throughput discovery technologies such as DNA microarrays in animal models can
      identify novel genes and regulatory networks that are important for disease
      manifestations and that may be targets for therapy. In this brief review, we
      highlight recent progress in the field and attempt to place the strengths and
      limitations of popular SSc murine models in perspective.

PMID- 18638425
TI  - Circulating progenitor cells and scleroderma.
AB  - Scleroderma (systemic sclerosis) is a disease of unknown origins that involves
      tissue ischemia and fibrosis in the skin and internal organs such as the lungs.
      The tissue ischemia is due to a lack of functional blood vessels and an inability
      to form new blood vessels. Bone marrow--derived circulating endothelial
      progenitor cells play a key role in blood vessel repair and neovascularization.
      Scleroderma patients appear to have defects in the number and function of
      circulating endothelial progenitor cells. Scleroderma patients also develop
      fibrotic lesions, possibly as the result of tissue ischemia. Fibroblast-like
      cells called fibrocytes that differentiate from a different pool of bone marrow
      derived circulating progenitor cells seem to be involved in this process.
      Manipulating the production, function, and differentiation of circulating
      progenitor cells represents an exciting new possibility for treating scleroderma.

PMID- 18638426
TI  - Cellular therapy of systemic sclerosis.
AB  - Cell-based therapies bear promise as a means to dampen autoaggressive immune
      reactions and induce tolerance in patients with severe rheumatic autoimmune
      diseases. Of the various types of cell-based therapies, immunoablative treatment
      combined with autologous hematopoietic stem cell transplantation has been used in
      more than 1000 patients with severe autoimmune diseases worldwide, including
      patients with rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus
      erythematosus, and systemic sclerosis. Long-term improvements of disease activity
      have been documented, albeit at the expense of treatment-related toxicity and
      mortality. Based on the results of pilot studies, prospective randomized
      controlled trials have been initiated to compare safety and efficacy of
      hematopoietic stem cell transplantation versus conventional treatment. Therapies
      involving mesenchymal stromal cells are currently being explored in clinical
      settings because of their anti-inflammatory and tissue regenerative properties
      and their favorable risk/benefit ratio.

PMID- 18638427
TI  - Nephrogenic systemic fibrosis: an epidemic of gadolinium toxicity.
AB  - Nephrogenic systemic fibrosis is a devastating systemic fibrosing disorder that
      afflicts patients with renal dysfunction. Growing evidence supports the
      hypothesis that gadolinium-containing contrast agents (GCCAs) trigger the
      development of nephrogenic systemic fibrosis. Hence, this condition is most
      appropriately called gadolinium---associated systemic fibrosis (GASF). In this
      report, we review the history of GASF, its association with prior GCCA exposure,
      its clinicopathologic features, the relevant pharmacology of GCCAs, the likely
      role of GCCAs in its pathogenesis, and potential treatments.

PMID- 18638428
TI  - Scleroderma gene expression and pathway signatures.
AB  - Gene expression studies in scleroderma have shown large and consistent changes in
      the gene expression of end-target tissues. These changes reflect the lymphocyte
      infiltration and pathway deregulation potentially linked to disease pathogenesis.
      Gene expression in scleroderma also reflects the clinical heterogeneity in the
      disease and can be used to categorize patients. Contained within these gene
      expression signatures are groups of genes that could serve as biomarkers for
      clinical end points and disease activity. The use of mechanism-derived gene
      expression signatures in scleroderma will provide a better understanding of the
      deregulated pathways contributing to disease pathogenesis.

PMID- 18638431
TI  - Colchicine: its mechanism of action and efficacy in crystal-induced inflammation.
AB  - New light has been shed on the mechanisms of action of colchicine in crystal
      associated arthropathies. Colchicine, long used to treat gout, arrests
      microtubule assembly and inhibits many cellular functions. At micromolar
      concentrations, it suppresses monosodium urate crystal-induced NACHT-LRR-PYD
      containing protein-3 (NALP3) inflammasome-driven caspase-1 activation, IL-1beta
      processing and release, and L-selectin expression on neutrophils. At nanomolar
      concentrations, colchicine blocks the release of a crystal-derived chemotactic
      factor from neutrophil lysosomes, blocks neutrophil adhesion to endothelium by
      modulating the distribution of adhesion molecules on the endothelial cells, and
      inhibits monosodium urate crystal-induced production of superoxide anions from
      neutrophils. Cyto-chrome P450 3A4, the multidrug transporter P-glycoprotein, and
      the drugs that bind these proteins influence its pharmacokinetics and
      pharmacodynamics. Trial evidence supports its efficacy in acute gout and in
      preventing gout flares, but it has narrow therapeutic index, and overdosage is
      associated with gastrointestinal, hepatic, renal, neuromuscular, and cerebral
      toxicity; bone marrow damage; and high mortality.

PMID- 18638432
TI  - Treating difficult crystal pyrophosphate dihydrate deposition disease.
AB  - Calcium pyrophosphate dihydrate deposition disease is a common and potentially
      severe metabolic arthropathy. Early disease (in patients </= 60 years old)
      requires a search for one of the associated metabolic conditions, particularly
      hemochromatosis. Treatment is primarily symptomatic (no drug is known to prevent
      the progression of articular destruction). Nonsteroidal anti-inflammatory drugs
      and intra-articular or systemic glucocorticoids (in small amounts if use is
      prolonged) are the most useful treatments. Colchicine can be effective to treat
      recurring pseudogout, and magnesium can be effective on a preventive basis.
      Methotrexate showed interesting effectiveness in a small, uncontrolled series,
      and it can be used in the event of failure of the other treatments.

PMID- 18638434
TI  - Gout and coronary artery disease: epidemiologic clues.
AB  - Gout is the leading cause of inflammatory arthritis, typically affecting men and
      characterized by intermittent, abrupt onset of intense inflammation. The
      association between gout, atherosclerosis, and vascular disease has been noted in
      medical literature since the end of the 19th century, yet it has not been well
      studied. This review critically appraises the few epidemiologic studies that ask
      if gout is a risk factor for coronary artery disease. An exhaustive literature
      search using search engines and cross-referencing found four major studies and
      several smaller studies that have evaluated gout as a risk factor for coronary
      artery disease. The available studies were too heterogeneous to permit formal
      meta-analysis. Although there are gaps in evidence pointing to a causative
      pathway, overall, evidence exists for a relationship between gouty arthritis and
      coronary artery disease independent of traditional risk factors.

PMID- 18638435
TI  - Evaluation of a targeted immunisation program for Aboriginal and Torres Strait
      Islander infants in an urban setting.
AB  - A conjugate pneumococcal vaccination program for Aboriginal and Torres Strait
      Islander children in an urban setting initially achieved poor uptake. A targeted
      intervention was developed to raise awareness among hospital staff, in general
      practice and in parents of eligible children. An evaluation of the intervention
      found moderate levels of increased awareness, use of promotional materials and an
      increase in vaccination. However, significant structural barriers remained.

PMID- 18638433
TI  - Non-crystalline and crystalline rheumatic disorders in chronic kidney disease.
AB  - Rheumatic syndromes are cause for morbidity in patients with end-stage renal
      disease. Recent advances in understanding the role of tissue remodeling have
      provided insight into the pathogenic mechanisms responsible for some of these
      manifestations. Here, we survey recent and clinically relevant advances in
      translational research that impact our understanding of rheumatic syndromes seen
      in patients with significant renal disease. The management of acute and chronic
      crystalline arthropathies in chronic kidney disease and hemodialysis patients is
      discussed.

PMID- 18638436
TI  - Aboriginal and Torres Strait Islander peoples at higher risk of invasive
      meningococcal disease in NSW.
AB  - OBJECTIVE: To assess the completeness of data describing Aboriginal and Torres
      Strait Islander status in NSW invasive meningococcal disease notifications and
      determine the relative risk for invasive meningococcal disease among Aboriginal
      and Torres Strait Islander peoples in NSW. METHODS: Surveillance data from the
      NSW Notifiable Diseases Database was reviewed for 5-year periods between 1991 and
      2005. RESULTS: Invalid and missing data on Aboriginal and Torres Strait Islander
      status decreased from 42% to 8% during the study period. Higher rates of disease
      were found in young children and significantly higher rates in Aboriginal and
      Torres Strait Islander children aged 0-4 years compared with their non-Aboriginal
      counterparts. CONCLUSION: Aboriginal and Torres Strait Islander children in NSW
      experience higher rates of notified invasive meningococcal disease than non
      Aboriginal children.

PMID- 18638437
TI  - Australian Bat Lyssavirus: examination of post-exposure treatment in NSW.
AB  - Ten years after the recognition of Australian Bat Lyssavirus, it is timely to
      review the occurrence of the virus in native microbat and flying fox species in
      Australia, and the effectiveness of post-exposure treatment in humans.
      Differences between post-exposure treatment protocols adopted by state and
      territory health departments were examined. In Queensland and the United States
      of America, post-exposure treatment is withheld in people who are bitten by bats
      that subsequently test negative for ABLV and rabies, respectively. The good
      outcomes from these protocols support the revised NSW policy, which delays post
      exposure treatment for up to 48 hours for minor exposures while awaiting bat test
      results. Post-exposure treatment can be withheld or ceased if the bat test result
      is negative.

PMID- 18638438
TI  - A mobility model for classical swine fever in feral pig populations.
AB  - We present a simulation model which explicitly captures the movement of wild
      animals over the landscape and the effect which herd mobility has on the temporal
      and spatial course of an epidemic. Using the example of classical swine fever in
      feral pig populations in the tropical savannas, we demonstrate that seasonal
      factors influencing population density and movement patterns are an important
      factor in the transmission of the disease. Pig population density is much greater
      at the start of the dry season than at the start of the wet season, with an
      epidemic most likely to occur if initiated at the start of the dry season.
      Spatial heterogeneity due to scarcity of water in the dry season causes herds to
      congregate around water sources. This concentration of herds, and the
      consequential isolation of sub-populations, reduces overall disease transmission
      compared with a model where the population is more evenly distributed over the
      landscape. The presence of adult male pig herds, which travel over greater
      distances than family herds, is shown to increase the overall scale of an
      outbreak in the dry season by connecting together otherwise isolated family
      herds. Eradication strategies are more likely to be successful in the dry season
      if they target long-range adult male herds. Our simulation method is generic and
      is equally applicable to other diseases where the host species is mobile.

PMID- 18638439
TI  - Membrane markers of the immune cells in swine: an update.
AB  - Besides their breeding value, swine are increasingly used as biomedical models.
      As reported in three international swine clusters of differentiation (CD)
      workshops and in the animal homologue section of the last workshop for the
      determination of human leukocyte differentiation antigens (HLDA 8),
      characterisation of leukocyte surface antigens by monoclonal antibodies and other
      molecular studies have determined the cell lineages and blood leukocyte subsets
      implicated in the immune response, including cell adhesion molecules involved in
      cell trafficking. This review focusses on the current state of knowledge of
      porcine leukocyte differentiation and major histocompatibility complex (SLA)
      molecules. Examples of porcine particularities such as the double-positive T
      lymphocytes with the phenotype CD(4+)CD8(low) and CD(4-)CD8(low) alphabeta T cell
      subsets and the persistence of SLA class II after T-lymphocyte activation are
      illustrated, as well as the shared characteristics of the Artiodactyla group,
      such as the high proportion of gammadelta TcR (T cell receptor) T cells in blood
      and other lymphoid tissues. Furthermore, discrepancies between swine and humans,
      such as CD16 expression on dendritic cells and CD11b (wCD11R1) tissue
      distribution are outlined. The rapidly growing information should facilitate
      manipulation of the swine immune system towards improving disease control, and
      open new avenues for biomedical research using the pig as a model.

PMID- 18638440
TI  - Membrane protein identifications by mass spectrometry using electrocapture-based
      separation as part of a two-dimensional fractionation system.
AB  - A two-dimensional (2D) separation method was used to decrease sample complexity
      in analysis of tryptic peptides from glomerular membrane proteins by tandem mass
      spectrometry (MS/MS). The first dimension was carried out by electrocapture (EC),
      which fractionates peptides according to electrophoretic mobility. The second
      dimension was reverse-phase liquid chromatography (RP-LC), in which EC fractions
      were further separated and analyzed online by MS/MS. Using this methodology, we
      now identify 102 glomerular proteins (57 membrane proteins). Many peptides were
      possible to observe and select for MS/MS only using the 2D approach. Others were
      detectable in both one-dimensional (1D, without the EC step) and 2D experiments
      but were selectable for sequence analysis only from the 2D separations because
      the decrease in complexity then gives time for the mass analyzer to select the
      peptide and switch to the MS/MS mode. A minority of the peptides were detectable
      only in the 1D mode (presumably because of handling losses), but at the end this
      did not decrease the number of proteins identified by the 2D separation. After a
      database search, the combination of EC and RP-LC MS/MS versus a 1D RP-LC MS/MS
      separation resulted in a threefold increase in the number of proteins identified
      and improved the sequence coverage in the identifications, bringing our proteome
      identified glomerular proteins to 282.

PMID- 18638441
TI  - Targeting DNA 5mCpG sites with chimeric endonucleases.
AB  - Cytosine modification of the dinucleotide CpG in the DNA regulatory region is an
      important epigenetic marker during early embryo development, cellular
      differentiation, and cancer progression. In clinical settings, such as anti
      cancer drug treatment, it is desirable to develop research tools to characterize
      DNA sequences affected by epigenetic perturbations. Here, we describe the
      construction and characterization of two fusion endonucleases consisting of the
      (5)mCpG-binding domain of human MeCP2 (hMeCP2) and the cleavage domains of BmrI
      and FokI restriction endonucleases (REases). The chimeric (CH) endonucleases
      cleave M.HpaII (C(5)mCGG)-and M.SssI ((5)mCpG)-modified DNA. Unmodified DNA and
      M.MspI-modified DNA ((5)mCCGG) are poor substrates for the CH-endonucleases.
      Sequencing cleavage products of modified lambda DNA indicates that cleavage takes
      place outside the (5)mCpG recognition sequence, predominantly 4-17 bp upstream of
      the modified base (/N(4-17)(5)mCpG, where / indicates the cleavage site). Such
      (5)mCpG-specific endonucleases will be useful to study CpG island modification of
      the regulatory regions of tumor suppressor genes, and for the construction of
      cell-specific and tumor-specific modified CpG island databases.

PMID- 18638442
TI  - An in vivo microdialysis coupled with liquid chromatography/tandem mass
      spectrometry study of cortisol metabolism in monkey adipose tissue.
AB  - It is postulated that elevated tissue concentrations of cortisol may be
      associated with the development of metabolic syndrome, obesity, and type 2
      diabetes. The 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme
      regenerates cortisol from inactive cortisone in tissues such as liver and
      adipose. To better understand the pivotal role of 11beta-HSD1 in disease
      development, an in vivo microdialysis assay coupled with liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) analysis using stable isotope
      labeled (SIL) cortisone as a substrate was developed. This assay overcomes the
      limitations of existing methodologies that suffer from radioactivity exposure and
      analytical assay sensitivity and specificity concerns. Analyte extraction
      efficiencies (E(d)) were evaluated by retrodialysis. The conversion of SIL
      cortisone to SIL-cortisol in rhesus monkey adipose tissue was studied. Solutions
      containing 100, 500, and 1000 ng/mL SIL-cortisone were locally delivered through
      an implanted 30-mm microdialysis probe in adipose tissue. At the delivery rate of
      1.0 and 0.5 microL/min, E(d) values for SIL-cortisone were between 58.7+/-5.6%
      (n=4) and 72.7+/-1.3% (n=4), whereas at 0.3 microL/min E(d) reached nearly 100%.
      The presence of 11beta-HSD1 activities in adipose tissue was demonstrated by
      production of SIL-cortisol during SIL-cortisone infusion. This methodology could
      be applied to cortisol metabolism studies in tissues of other mammalian species.

PMID- 18638443
TI  - Development of a high-performance liquid chromatography-based assay for
      carotenoids in human red blood cells: application to clinical studies.
AB  - Peroxidized phospholipid-mediated cytotoxicity is involved in the pathophysiology
      of many diseases; for example, there is an abnormal increase of phospholipid
      hydroperoxides in red blood cells (RBCs) of dementia patients. Dietary
      carotenoids have gained attention as potent inhibitors of RBC phospholipid
      hydroperoxidation, thereby making them plausible candidates for preventing
      disease. However, the occurrence of carotenoids in human RBCs is still unclear.
      This is in contradistinction to plasma carotenoids, which have been investigated
      thoroughly for analytical methods as well as biological significance. In this
      study, we developed a method to analyze RBC carotenoids using high-performance
      liquid chromatography (HPLC) coupled with ultraviolet (UV) diode array detection
      (DAD) and atmospheric pressure chemical ionization (APCI) mass spectrometry (MS).
      Under optimized conditions that included extraction, separation, and detection
      procedures, six carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, alpha
      carotene, beta-carotene, and lycopene) were separated, detected by DAD, and
      concurrently identified based on APCI/MS and UV spectra profiles when an extract
      from human RBCs was subjected to HPLC-DAD-APCI/MS. The amounts of carotenoids
      varied markedly (1.3-70.2 nmol/L packed cells), and polar oxygenated carotenoids
      (xanthophylls) were predominant in RBCs. The HPLC-DAD-APCI/MS method would be a
      useful tool for clinical studies for evaluating the bioavailability of RBC
      carotenoids.

PMID- 18638444
TI  - Flow cytometry for real-time measurement of guanine nucleotide binding and
      exchange by Ras-like GTPases.
AB  - Ras-like small GTPases cycle between GTP-bound active and GDP-bound inactive
      conformational states to regulate diverse cellular processes. Despite their
      importance, detailed kinetic or comparative studies of family members are rarely
      undertaken due to the lack of real-time assays measuring nucleotide binding or
      exchange. Here we report a bead-based flow cytometric assay that quantitatively
      measures the nucleotide binding properties of glutathione-S-transferase (GST)
      chimeras for prototypical Ras family members Rab7 and Rho. Measurements are
      possible in the presence or absence of Mg(2+), with magnesium cations principally
      increasing affinity and slowing nucleotide dissociation rates 8- to 10-fold. GST
      Rab7 exhibited a 3-fold higher affinity for guanosine diphosphate (GDP) relative
      to guanosine triphosphate (GTP) that is consistent with a 3-fold slower
      dissociation rate of GDP. Strikingly, GST-Rab7 had a marked preference for GTP
      with ribose ring-conjugated BODIPY FL. The more commonly used gamma-NH-conjugated
      BODIPY FL GTP analogue failed to bind to GST-Rab7. In contrast, both BODIPY
      analogues bound equally well to GST-RhoA and GST-RhoC. Comparisons of the GST
      Rab7 and GST-RhoA GTP binding pockets provide a structural basis for the observed
      binding differences. In sum, the flow cytometric assay can be used to measure
      nucleotide binding properties of GTPases in real time and to quantitatively
      assess differences between GTPases.

PMID- 18638445
TI  - Method to eliminate linear DNA from mixture containing nicked circular,
      supercoiled, and linear plasmid DNA.
AB  - Preparations of circular plasmid DNA in either supercoiled or nicked circular
      form often are contaminated with undesired linear DNA fragments arising from
      shearing/degradation of chromosomal DNA or linearization of plasmid DNA itself.
      We report a simple enzymatic method, using a combination of lambda exonuclease
      and RecJ(f), for the selective removal of linear DNA from such mixtures. lambda
      exonuclease digests one strand of linear duplex DNA in the 5' to 3' direction,
      whereas RecJ(f), a single-strand-specific exonuclease, digests the remaining
      complementary single strand into mononucleotides. This combination of
      exonucleases can remove linear DNA from a mixture of linear and supercoiled DNA,
      leaving the supercoiled form intact. Furthermore, the inability of lambda
      exonuclease to initiate digestion at nicks or gaps enables the removal of
      undesired linear DNA when nicked circular DNA has been enzymatically prepared
      from supercoiled DNA. This method can be useful in the preparation of homogeneous
      circular plasmid DNA required for therapeutic applications and biophysical
      studies.

PMID- 18638446
TI  - Expression and function of TETRAN, a new type of membrane transporter.
AB  - In contrast to transport across basolateral membranes, the mechanism governing
      transport of organic anions across the luminal membranes of proximal tubules has
      remained unclear. We recently found Tetracycline transporter-like protein
      (TETRAN), a human ortholog of yeast Tpo1p that can transport anionic Non
      steroidal anti-inflammatory drugs (NSAIDs). In this study, we examine the
      expression and function of TETRAN. TETRAN mRNA is expressed in various human
      tissues, including kidney. When overexpressed in cultured cells, TETRAN was
      predominantly localized on cytoplasmic membranes. Immunohistochemical analysis of
      human and mouse kidney tissue showed that TETRAN was expressed at the luminal
      membranes of proximal tubules. Overexpression of TETRAN in cultured cells
      facilitated the uptake of organic anions such as indomethacin (a NSAID) and
      fluorescein. The results suggest that TETRAN is a novel human organic anion
      transporter, and that it serves as a transporter for some NSAIDs and various
      other organic anions at the final excretion step.

PMID- 18638447
TI  - The AP-1 site is essential for the promoter activity of NOX1/NADPH oxidase, a
      vascular superoxide-producing enzyme: Possible involvement of the ERK1/2-JunB
      pathway.
AB  - NADPH oxidase is a major source of the superoxide produced in cardiovascular
      tissues. The expression of NOX1, a catalytic subunit of NADPH oxidase, is induced
      by various vasoactive factors, including angiotensin II, prostaglandin (PG)
      F(2alpha), and platelet-derived growth factor (PDGF). It was reported previously
      that the inducible expression of NOX1 is governed by the activating transcription
      factor-1 (ATF-1)-myocyte enhancer factor 2B (MEF2B) cascade downstream of
      phosphoinositide 3 (PI3) kinase. It was also reported that extracellular signal
      regulated kinase (ERK) 1/2 is involved in the expression of NOX1. To further
      clarify the factors involved in NOX1 induction downstream of ERK1/2, the promoter
      region of the NOX1 gene was analyzed. A consensus activator protein-1 (AP-1) site
      was found at -98/-92 in the 5'-flanking region of the rat NOX1 gene. The
      introduction of mutations at this site abolished PGF(2alpha)-induced
      transcriptional activation in a luciferase assay. Electrophoresis mobility shift
      assays demonstrated that PGF(2alpha) and PDGF augmented the binding of JunB to
      this sequence. PD98059, an inhibitor of MAPK/ERK kinase, suppressed the
      expression of JunB induced by PGF(2alpha) or PDGF. These results suggest that the
      ERK1/2-JunB pathway is a key regulator of the inducible expression of the NOX1
      gene in vascular smooth muscle cells.

PMID- 18638448
TI  - Ferric reductase activity of low molecular weight human milk fraction is
      associated with enhanced iron solubility and uptake in Caco-2 cells.
AB  - It is known that the fractional absorption of extrinsic iron from human milk is
      higher in infants and adults. A low molecular weight milk fraction has been
      proposed to increase the bioavailability of iron from human milk. Nevertheless,
      the mechanisms remained elusive. Here in we demonstrate ferric reductase activity
      (Km7.73x10(-6)M) in low molecular weight human milk fraction (10kF, filtrate
      derived from ultra filtration of milk whey through 10kDa cutoff membrane), which
      increased ferric iron solubility and iron uptake in Caco-2 cells. The 10kF
      fraction was as effective as ascorbic acid (1:20 iron to ascorbic acid) in
      increasing the ferric iron solubility and uptake in Caco-2 cells. Further, gel
      filtration chromatography on peptide column led to co-elution of ferric reductase
      and iron solubilization activities at an apparent molecular mass of <1500Da.
      Interestingly, only these fractions containing ferric reductase activity also
      stimulated the uptake of iron in Caco-2 cells. Thus, it is concluded that human
      milk possesses ferric reductase activity and is associated with ferric iron
      solubilization and enhanced absorption.

PMID- 18638449
TI  - Identification of lutein, a dietary antioxidant carotenoid in guinea pig tissues.
AB  - Lutein, a dietary carotenoid, is a well known antioxidant. The major source of
      this carotenoid in humans is diet. We report here the presence of lutein, a
      dietary carotenoid in several guinea pig tissues (in decreasing order:
      liver>spleen>lung>>testis>kidney>plasma>eye but not in white adipose tissue). The
      presence of lutein in lung and other tissues may be significant in term of its
      antioxidant capacity of these organs.

PMID- 18638450
TI  - Lycopene suppresses ovalbumin-induced airway inflammation in a murine model of
      asthma.
AB  - In this study, we attempt to determine whether lycopene regulates inflammatory
      mediators in the ovalbumin (OVA)-induced murine asthma model. To address this,
      mice were sensitized and challenged with OVA, and then treated with lycopene
      before the last OVA challenge. Administration of lycopene significantly
      alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine.
      Administration of lycopene also resulted in a significant inhibition of the
      infiltration of inflammatory immunocytes into the bronchoalveolar lavage, and
      attenuated the gelatinolytic activity of matrix metalloproteinase-9 and the
      expression of eosinophil peroxidase. Additionally, lycopene reduced the increased
      levels of GATA-3 mRNA level and IL-4 expression in OVA-challenged mice. However,
      it increased T-bet mRNA level and IFN-gamma expression in lycopene-challenged
      mice. These findings provide new insight into the immunopharmacological role of
      lycopene in terms of its effects in a murine model of asthma.

PMID- 18638451
TI  - Induction of autophagy by proteasome inhibitor is associated with proliferative
      arrest in colon cancer cells.
AB  - The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy
      (autophagy) are two major intracellular pathways for protein degradation.
      Blockade of UPS by proteasome inhibitors has been shown to activate autophagy.
      Recent evidence also suggests that proteasome inhibitors may inhibit cancer
      growth. In this study, the effect of a proteasome inhibitor MG-132 on the
      proliferation and autophagy of cultured colon cancer cells (HT-29) was
      elucidated. Results showed that MG-132 inhibited HT-29 cell proliferation and
      induced G(2)/M cell cycle arrest which was associated with the formation of
      LC3(+) autophagic vacuoles and the accumulation of acidic vesicular organelles.
      MG-132 also increased the protein expression of LC3-I and -II in a time-dependent
      manner. In this connection, 3-methyladenine, a Class III phosphoinositide 3
      kinase inhibitor, significantly abolished the formation of LC3(+) autophagic
      vacuoles and the expression of LC3-II but not LC3-I induced by MG-132. Taken
      together, this study demonstrates that inhibition of proteasome in colon cancer
      cells lowers cell proliferation and activates autophagy. This discovery may shed
      a new light on the novel function of proteasome in the regulation of autophagy
      and proliferation in colon cancer cells.

PMID- 18638452
TI  - Acidic domain is indispensable for MDM2 to negatively regulate the acetylation of
      p53.
AB  - MDM2 is the most important negative regulator of tumor suppressor p53. Both RING
      finger domain and acidic domain of MDM2 contribute to the ubiquitination of p53.
      The crosstalk between ubiquitination and acetylation of p53 prompts us to examine
      whether acidic domain is essential for MDM2 to regulate the acetylation of p53.
      We find that the acidic domain of MDM2 is necessary to inhibit p300-mediated
      acetylation of p53 as well as to mediate the deacetylation of p53. Our results
      indicate that acidic domain of MDM2 provides essential information for
      acetyltransferase p300 and deacetylase HDAC1 and is indispensable for MDM2 to
      negatively regulate the acetylation of p53.

PMID- 18638453
TI  - Detection of myosin light chain phosphorylation--a cell-based assay for screening
      Rho-kinase inhibitors.
AB  - Here, we describe the first example of a cell-based myosin light chain
      phosphorylation assay in 96-well format that allows for the rapid screening of
      novel Rho-kinase inhibitors. We obtained IC(50) values for the prototypic Rho
      kinase inhibitors Y-27632 (1.2+/-0.05microM) and Fasudil (3.7+/-1.2microM) that
      were similar to those previously published utilizing electrophoresis-based
      methodologies. H-1152P, a Fasudil analog showed an IC(50) value of 77+/-30nM.
      Data derived from a set of 21 novel Rho-kinase inhibitors correlate with those
      generated by a well-established cell-based phenotypic Rho-kinase inhibition assay
      (R(2)=0.744). These results show that imaging technology measuring changes in
      myosin light chain phosphorylation can be used to rapidly generate quantitative
      IC(50) values and to screen a larger set of small molecule Rho-kinase inhibitors
      and suggests that this approach can be broadly applied to other cell lines and
      signaling pathways.

PMID- 18638454
TI  - Inflammation stimulates the expression of PCSK9.
AB  - Inflammation induces marked changes in lipid and lipoprotein metabolism.
      Proprotein convertase subtilisin kexin 9 (PCSK9) plays an important role in
      regulating LDL receptor degradation. Here, we demonstrate that LPS decreases
      hepatic LDL receptor protein but at the same time hepatic LDL receptor mRNA
      levels are not decreased. We therefore explored the effect of LPS on PCSK9
      expression. LPS results in a marked increase in hepatic PCSK9 mRNA levels (4h 2.5
      fold increase; 38h 12.5-fold increase). The increase in PCSK9 is a sensitive
      response with 1microg LPS inducing a (1/2) maximal response. LPS also increased
      PCSK9 expression in the kidney. Finally, zymosan and turpentine, other treatments
      that induce inflammation, also stimulated hepatic expression of PCSK9. Thus,
      inflammation stimulates PCSK9 expression leading to increased LDL receptor
      degradation and decreasing LDL receptors thereby increasing serum LDL, which
      could have beneficial effects on host defense.

PMID- 18638455
TI  - Purification of the functional plant membrane channel KAT1.
AB  - The inward-rectifying K(+) channel KAT1 is expressed mainly in Arabidopsis
      thaliana guard cells. The purification of functional KAT1 has never been
      reported. We investigated the extraction of the plant K(+) channel KAT1 with
      different detergents, as an example for how to select detergents for purifying a
      eukaryotic membrane protein. A KAT1-GFP fusion protein was used to screen a
      library of 46 detergents for the effective solubilization of intact KAT1. Then, a
      "test set" of three detergents was picked for further analysis, based on their
      biochemical characteristics and availability. The combination use of the selected
      detergents enabled the effective purification of functional KAT1 with affinity
      and gel-filtration chromatography.

PMID- 18638456
TI  - AMPK represses TOP mRNA translation but not global protein synthesis in liver.
AB  - The AMP-activated protein kinase (AMPK) represses signaling through the mammalian
      target of rapamycin complex 1 (mTORC1). In muscle, repression of mTORC1 leads to
      a reduction in global protein synthesis. In contrast, repression of mTORC1 in the
      liver has no immediate effect on global protein synthesis. In the present study,
      signaling through mTORC1 and translation of specific mRNAs such as those bearing
      a 5'-terminal oligopyrimidine (TOP) tract and were examined in rat liver
      following activation of AMPK after treadmill running. Activation of AMPK
      repressed translation of the TOP mRNAs encoding rpS6, rpS8, and eEF1alpha. In
      contrast, neither global protein synthesis nor translation of mRNAs encoding
      GAPDH or beta-actin was changed. Basal phosphorylation of the mTORC1 target 4E
      BP1, but not S6K1 or rpS6, was reduced following activation of AMPK. Thus, in
      liver, AMPK activation repressed translation of TOP mRNAs through a mechanism
      distinct from downregulated phosphorylation of S6K1 or rpS6.

PMID- 18638457
TI  - Bcl-2 family members as molecular targets in cancer therapy.
AB  - Escape from apoptosis is often a hallmark of cancer cells, and is associated to
      chemotherapy resistance or tumor relapse. Proteins from the Bcl-2 family are the
      key regulators of the intrinsic pathway of apoptosis, controlling the point-of no
      return and setting the threshold to engage the death machinery in response to a
      chemical damage. Therefore, Bcl-2 proteins have emerged as an attractive target
      to develop novel anticancer drugs. Current pharmacological approaches are focused
      on the use of peptides, small inhibitory molecules or antisense oligonucleotides
      to neutralize antiapoptotic Bcl-2 proteins, lowering the threshold and
      facilitating apoptosis of cancer cells. We discuss here recent advances in the
      development of Bcl-2 targeted anticancer therapies.

PMID- 18638458
TI  - Differential regulation of osteopontin receptors, CD44 and the alpha(v) and
      beta(3) integrin subunits, in the rat hippocampus following transient forebrain
      ischemia.
AB  - We have examined the spatiotemporal regulation of CD44 and the alpha(v)beta(3)
      integrin subunits, which have been identified as receptors for osteopontin (OPN),
      in the rat hippocampus following transient forebrain ischemia. Immunoreactivity
      for CD44 and the integrin subunits, alpha(v) and beta(3), showed characteristic
      time- and cell-dependent patterns in the ischemic hippocampus. CD44
      immunoreactivity was induced at day 1 after reperfusion, reached a peak at day 3,
      and returned to basal levels by day 7. CD44 was induced in a subset of activated
      microglial cells within sites of intense neural damage, and the concomitant
      induction of OPN and CD44 was observed in the same cells in the ischemic
      hippocampus. In contrast, increased immunoreactivity for alpha(v) and beta(3),
      which shared overlapping expression patterns in the ischemic hippocampus,
      occurred in the majority of reactive astrocytes and only a few microglia at day 3
      after reperfusion, and was sustained for more than 2 weeks. Immunoreactivity for
      both integrin subunits colocalized with OPN immunoreactivity in reactive
      astrocytes, and OPN immunoreactivity was also diffusely localized over the
      extracellular matrix around the reactive astrocytes. These data indicated that
      the rapid and transient induction of CD44 and OPN occurred in activated
      microglia/macrophages, whereas the long-lasting induction of alpha(v) and beta(3)
      integrin subunits and OPN occurred in reactive astrocytes, suggesting that the
      multifunctional role of OPN in the ischemic brain may be attributed, in part, to
      a time- and cell-dependent interaction with CD44 or integrin alpha(v)beta(3).

PMID- 18638460
TI  - Oscillations in "brain-body-mind"--a holistic view including the autonomous
      system.
AB  - Studies related to brain oscillations pervade the neuroscience literature.
      Functional correlates of oscillations in the delta, theta, alpha, beta and gamma
      frequency windows are interpreted in several ways. However, only a small number
      of reports indicate the need for overall interpretations by integrating all type
      of results. The present essay emphasizes the importance of developing a common
      overview by considering sensory and cognitive inputs, in studies comparing
      healthy subjects with subjects with cognitive impairments. By doing this, the
      present report briefly outlines some general aspects and rules in the study of
      brain oscillations. The use in clinical studies of drugs mimicking
      neurotransmitters is also taken into consideration for a more complete analysis.
      A prominent extension to the study of functional correlates of brain functions is
      the new emerging results in oscillatory processes in the spinal cord and the
      autonomous system. By integrating oscillations in all EEG frequency windows,
      together with oscillations in the spinal cord and the autonomous system, a
      Gedanken-Model denoted as "globally coupled oscillators" of brain-body-mind
      incorporation is proposed in order to gain new insights in the dynamics of neural
      systems.

PMID- 18638459
TI  - MDMA treatment 6 months earlier attenuates the effects of CP-94,253, a 5-HT1B
      receptor agonist, on motor control but not sleep inhibition.
AB  - The possible long-term effects of the recreational drug "ecstasy" (3,4
      methylenedioxymethamphetamine, MDMA) on the function of 5-hydroxytryptamine-1B (5
      HT(1B)) receptor in sleep and motor control were investigated using a selective 5
      HT(1B) receptor agonist, 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyrinzidyl)-1H
      pyrrolo([3,2-b])pyridine hydrochloride (CP-94,253; 5 mg/kg). CP-94,253 or vehicle
      was administered to freely moving rats pre-treated with MDMA (15 mg/kg) or
      vehicle 6 months earlier, and polygraphic recording for 24 h and motor activity
      measurements were performed. Active wake (AW), passive wake (PW), light slow wave
      sleep (SWS-1), deep slow wave sleep (SWS-2), paradoxical sleep (PS), and diurnal
      rhythm were analyzed for the whole period. In additional, the EEG power spectrum
      was calculated for the second hour after the acute treatment for AW, PW, SWS-1,
      and SWS-2. 5-HT transporter (5-HTT) immunohistochemistry was measured in brain
      areas related to sleep and motor control 6 months after MDMA treatment. CP-94,253
      increased AW and PW, decreased SWS-2 and PS, and altered parameters of diurnal
      rhythm in control animals. CP-94,253 decreased the EEG power spectra at higher
      frequencies. The effects of CP-94,253 on AW and diurnal rhythm were reduced or
      eliminated in MDMA-treated animals. MDMA treatment decreased 5-HTT fibre density
      in posterior hypothalamus, tuberomammillary nucleus, caudate putamen and
      ventrolateral striatum. These data suggest that long-term changes in 5-HT(1B)
      receptor function occur after serotonergic damage caused by a single dose of
      MDMA.

PMID- 18638461
TI  - Selective effects of auditory stimuli on tactile roughness perception.
AB  - We report two psychophysical experiments designed to investigate the effects of
      non touch-produced sounds on the tactile perception of roughness and length.
      Previous studies have demonstrated that the tactile roughness perception of
      object surfaces is modified by sounds elicited by rubbing the surfaces. In this
      study, we examined the crossmodal effects of non touch-produced sounds such as
      white noise (Experiment 1) and pure tones (Experiment 2). Participants touched
      abrasive paper, synchronizing their touch with changes in the intensity of sounds
      or with the onset of beeps (control condition), and judged the tactile roughness
      or length of the stimuli, using the magnitude estimation method. Although the
      white noise (complex sound) significantly decreased the slope of the roughness
      estimation function, it did not affect that of the length estimation function.
      Pure tones had no effect on roughness or length perception. The results revealed
      that complex sounds selectively affected tactile roughness perception, even when
      they were seemingly irrelevant to the exploration of the surfaces. We suggest
      that the processing of complex sounds may be related to the processing of tactile
      roughness, whereas it is independent of tactile length processing.

PMID- 18638462
TI  - Novel indoloquinoline derivative, IQDMA, suppresses STAT5 phosphorylation and
      induces apoptosis in HL-60 cells.
AB  - Signal transducers and activators of transcription (STATs) are a family proteins
      that mediate cytokine and growth factor-induced signals playing a role in cell
      differentiation, proliferation, angiogenesis, and apoptosis. One STAT family
      member, STAT5, is often constitutively active in myeloid leukaemia. Agents that
      can suppress STAT5 activation have potential for prevention and treatment of
      cancer. N'-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-dia-mine
      (IQDMA), an indoloquinoline derivative, synthesized in our laboratory, has been
      demonstrated to be an effective anti-tumor agent in human leukemia cells. In the
      present report, we tested IQDMA for its ability to suppress STAT5 activation. We
      found that IQDMA inhibited constitutive activation of STAT5 in HL-60 cells in a
      dose- and time-dependent manner. The activation of Src and interleukin-6 (IL-6),
      implicated in STAT5 activation, was also inhibited by the IQDMA. Furthermore,
      IQDMA up-regulated Bax, and down-regulated Bcl-2, Bcl-X(L), cyclin D1, and
      vascular endothelial growth factor (VEGF) as followed by growth arrest of HL-60
      cells, but the expression of survivin did not change in the presence of IQDMA.
      Taken together, these results indicate that IQDMA causes significant induction of
      apoptosis in HL-60 cells via down-regulation of Src, IL-6, and STAT5 signaling
      and modulation of Bcl-2 family, cyclin D1 and VEGF proteins. Thus, IQDMA appears
      to be a potential therapeutic agent for treating leukaemia HL-60 cells.

PMID- 18638463
TI  - Chloro acridone derivatives as cytotoxic agents active on multidrug-resistant
      cell lines and their duplex DNA complex studies by electrospray ionization mass
      spectrometry.
AB  - We report herein in vitro anti-proliferative activity and duplex DNA complex
      studies of a series of N10-substituted acridone derivatives. All the molecules
      have been designed on the basis of the presence of specific recognition patterns
      consisting of hydrogen bond acceptors (or electron donors), carbonyl, chloro
      groups with precise spatial separation and structural features (lipophilicity,
      positive charge at neutral pH and presence of aromatic rings). The in vitro
      cytotoxic effects have been demonstrated against human promyelocytic leukemia
      sensitive cell line (HL-60), including its multidrug cross-resistance of two main
      (P-gp and MRP) phenotype sublines vincristine-resistant (HL-60/VINC) and
      doxorubicin-resistant (HL-60/DX) cancer cell lines. Compound 4 showed very good
      activity against sensitive and resistant cell lines. The noncovalent complexes of
      these molecules with DNA duplex has been investigated in gas phase by using a
      fast, robust and sensitive electrospray ionization mass spectrometry (ESI-MS)
      technique. Equilibrium association constants (K1) and percentage of intact
      complexes were determined. The combined results show that these acridone
      derivatives interact with DNA duplex by intercalation between the base pairs,
      possess higher affinity to GC than AT base pairs of the DNA and they could not
      interact noncovalently with the minor grooves of the DNA in solution-free gas
      phase. Examination of the relationship between lipophilicity and cytotoxic
      properties of acridone derivatives showed a poor correlation. The in vitro
      cytotoxic studies in resistant cancer cell lines of compound 4 showed that it
      might be a promising new hit for further development of anti-MDR agent.

PMID- 18638464
TI  - Increased glycated albumin and decreased esRAGE concentrations are associated
      with in-stent restenosis in Chinese diabetic patients.
AB  - BACKGROUND: We investigated the impact of glycated albumin (GA) and endogenous
      secretory receptor for advanced glycation end products (esRAGE) and RAGE
      polymorphisms on occurrence of in-stent restenosis (ISR) in Chinese patients with
      type 2 diabetes. METHODS: Four hundred nineteen patients with diabetes were
      divided, based upon the presence or absence of coronary artery disease (CAD) and
      ISR, into Group I (205 patients without CAD), Group II (128 patients with CAD but
      without ISR) and Group III (86 patients with ISR). One hundred fifty-two normal
      subjects were served as controls. Serum concentrations of GA and esRAGE were
      measured, and RAGE polymorphisms (-374T>A, -429T>C and G82S) were analyzed.
      RESULTS: Serum GA concentration was higher and, in contrast, esRAGE concentration
      was lower in Group III than in the other groups (P<0.05). These two protein
      concentrations correlated closely with loss index (all P<0.01), and were
      independent risk factors for ISR in diabetic patients (P=0.01 and P=0.025,
      respectively). However, there were no differences in the allele and genotype
      frequencies in the 3 polymorphisms of RAGE gene between groups. CONCLUSIONS:
      Increased GA and decreased esRAGE concentrations, but not -374T>A, -429T>C and
      Gly82Ser polymorphisms of RAGE gene, are associated with ISR in Chinese patients
      with type 2 diabetes.

PMID- 18638465
TI  - Pseudohyperkalemia--is serum or whole blood a better specimen type than plasma?

PMID- 18638466
TI  - Anti-cyclic citrullinated peptide antibodies in lung diseases associated with
      rheumatoid arthritis.
AB  - OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly
      specific markers for rheumatoid arthritis (RA) and useful for predicting RA
      development and progression. However, it has not been fully determined whether
      anti-CCP antibodies are associated with pulmonary diseases in RA patients. In the
      present study, we aimed to elucidate the relationships between anti-CCP
      antibodies and pulmonary diseases, particularly interstitial lung disease (ILD)
      and bronchiolitis. DESIGN AND METHODS: Using an enzyme-linked immunosorbent
      assay, the presence of serum anti-CCP antibodies was examined in 18 RA patients
      with ILD and bronchiolitis who were diagnosed based on pathologic findings. A
      further 36 RA subjects without any pulmonary diseases served as a reference
      population. RESULTS: No significant differences were found for the prevalences
      and levels of anti-CCP antibodies between patients with and without ILD and
      follicular bronchiolitis. CONCLUSION: Detection of serum anti-CCP antibodies has
      no association with pulmonary diseases in RA patients.

PMID- 18638467
TI  - Analytical investigation: assay of D-lactate in diabetic plasma and urine.
AB  - OBJECTIVE: In this study we developed a 96-micro plate enzymatic assay for D
      lactate in plasma and urine. METHODS: D-lactate was assayed enzymatically with a
      UV-spectrophotometer in plasma from 38 and in urine from 37 diabetics and from 42
      non-diabetic controls. RESULTS: The within-run coefficients of variations (CV)
      were 2.6% for plasma and 5.7% for urine. The between run CVs were 6.8% for plasma
      and 6.7% for urine. The mean recovery with standard deviation (S.D.) was 107.4+/
      7.3% for plasma and 100.1%+/-6.7% for urine. The plasma D-lactate in diabetics
      were (mean+/-S.D.) 39.6+/-23.7 microM. We found significant difference between
      the urinary d-lactate in controls and diabetics (18.2+/-12.0 vs. 35.9+/-24.2
      microM/mM creatinine, p<0.0001). CONCLUSIONS: The assay proved reliable with
      acceptable precision and recovery. Results suggest that diabetics have elevated
      urinary and plasma D-lactate as compared to controls.

PMID- 18638468
TI  - A new protein carrying an NmrA-like domain is required for cell differentiation
      and development in Dictyostelium discoideum.
AB  - We have isolated a Dictyostelium mutant unable to induce expression of the
      prestalk-specific marker ecmB in monolayer assays. The disrupted gene, padA,
      leads to a range of phenotypic defects in growth and development. We show that
      padA is essential for growth, and we have generated a thermosensitive mutant
      allele, padA(-). At the permissive temperature, mutant cells grow poorly; they
      remain longer at the slug stage during development and are defective in terminal
      differentiation. At the restrictive temperature, growth is completely blocked,
      while development is permanently arrested prior to culmination. padA(-) slugs are
      deficient in prestalk A cell differentiation and present an abnormal ecmB
      expression pattern. Sequence comparisons and predicted three-dimensional
      structure analyses show that PadA carries an NmrA-like domain. NmrA is a negative
      transcriptional regulator involved in nitrogen metabolite repression in
      Aspergillus nidulans. PadA predicted structure shows a NAD(P)(+)-binding domain,
      which we demonstrate that is essential for function. We show that padA(-)
      development is more sensitive to ammonia than wild-type cells and two ammonium
      transporters, amtA and amtC, appear derepressed during padA(-) development. Our
      data suggest that PadA belongs to a new family of NAD(P)(+)-binding proteins that
      link metabolic changes to gene expression and is required for growth and normal
      development.

PMID- 18638469
TI  - Tri-phasic expression of posterior Hox genes during development of pectoral fins
      in zebrafish: implications for the evolution of vertebrate paired appendages.
AB  - During development of the limbs, Hox genes belonging to the paralogous groups 9
      13 are expressed in three distinct phases, which play key roles in the segmental
      patterning of limb skeletons. In teleost fishes, which have a very different
      organization in their fin skeletons, it is not clear whether a similar patterning
      mechanism is at work. To determine whether Hox genes are also expressed in
      several distinct phases during teleost paired fin development, we re-analyzed the
      expression patterns of hox9-13 genes during development of pectoral fins in
      zebrafish. We found that, similar to tetrapod Hox genes, expression of hoxa/d
      genes in zebrafish pectoral fins occurs in three distinct phases, in which the
      most distal/third phase is correlated with the development of the most distal
      structure of the fin, the fin blade. Like in tetrapods, hox gene expression in
      zebrafish pectoral fins during the distal/third phase is dependent upon sonic
      hedgehog signaling (hoxa and hoxd genes) and the presence of a long-range
      enhancer (hoxa genes), which indicates that the regulatory mechanisms underlying
      tri-phasic expression of Hox genes have remained relatively unchanged during
      evolution. Our results suggest that, although simpler in organization, teleost
      fins do have a distal structure that might be considered comparable to the
      autopod region of limbs.

PMID- 18638470
TI  - pH dependent efflux of methamphetamine derivatives and their reversal through
      human Caco-2 cell monolayers.
AB  - The purpose of this study was to investigate possible efflux mechanisms involved
      in amphetamine derivative transport such as for 3,4-methylenedioxymethamphetamine
      (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), para-methoxyamphetamine (p
      MA), dexamphetamine and pseudoephedrine, especially across pH gradients that
      exist in intestinal or kidney transport. This was determined using our Caco-2
      subclone, CLEFF9. Transport of the amphetamine derivatives was evaluated at pH
      7.4 and pH 6/7.4+/-efflux inhibitors. Na+-H+ transporter inhibition via carbonyl
      cyanide-4-trifluoromethoxy phenylhydrazone (FCCP), and metabolic inhibition using
      Na-azide and Na-orthovanadate were also conducted, as well as using noradrenalin,
      adrenalin and other inhibitors of a range of carrier mediated transport systems
      such as histamine, organic cation transporters and dopamine carrier systems. At
      pH 7.4, the rate of transport for dexamphetamine, pseudoephedrine and MDMA in
      both apical to basolateral and reverse directions was all very rapid, confirming
      extensive passive diffusion at systemic pH. However, creating a pH 6.0/7.4
      gradient showed marked increase in basolateral to apical transport of all
      amphetamines tested, with dexamphetamine, MDEA, MDMA and p-MA having a net efflux
      ratio of around 16, 14, 13 and 11 respectively and this was not reversed with P
      glycoprotein inhibitors. Azide, FCCP, adrenalin, noradrenalin and reserpine were
      able to reduce the efflux by 2 to 3 fold, although tetraethylammonium could not.
      This suggested that extraneuronal monoamine transporters (hEMT) could be
      involved. This data suggests that elevated endogenous adrenalin levels may reduce
      amphetamine removal from the body based on these in vitro studies. Also, the use
      of stomach acid lowering drugs could result in more rapid systemic uptake of
      these amphetamine derivatives.

PMID- 18638471
TI  - The P2Y14 receptor activity in glioma C6 cells.
AB  - In this study, we demonstrated the presence and the activity of the P2Y14
      receptor in glioma C6 cells. We found that P2Y14 could exist in two forms, highly
      predominating glycosylated and non-glycosylated. Binding of UDP-glucose evoked
      two responses: calcium signal and adenylate cyclase inhibition, both pertussis
      toxin-sensitive. Separate glycosylation pattern and functional profile of these
      two receptor forms were observed in non-starved and serum-starved cells. During
      long-term serum deprivation (96 h), the level of glycosylated form strongly
      decreased, while non-glycosylated increased, what was correlated with the
      decrease of calcium signaling activity and stronger adenylate cyclase inhibition,
      suggesting that receptor N-glycosylation may modulate its functional activity.

PMID- 18638472
TI  - Anti-inflammatory treatment with the p38 mitogen-activated protein kinase
      inhibitor SB239063 is neuroprotective, decreases the number of activated
      microglia and facilitates neurogenesis in oxygen-glucose-deprived hippocampal
      slice cultures.
AB  - We investigated the effect of the p38 mitogen-activated protein kinase inhibitor
      SB239063 on inflammation and neurogenesis after ischemia in organotypic
      hippocampal slice cultures. Our study shows that after oxygen-glucose
      deprivation, the p38 mitogen-activated protein kinase (MAPK) and the
      extracellular-signal-regulated kinase 1/2 (ERK1/2) are strongly activated. The
      p38 MAPK phosphorylation returned to basal levels within 1 h after oxygen-glucose
      deprivation, whereas the ERK1/2 phosphorylation reached the basal level only
      after 24 h. Treatment with 20 microM and 100 microM SB239063 strikingly reduced
      cell death after oxygen-glucose deprivation and significantly diminished
      microglia activation in the cornu ammonis (CA-region), but not in the area
      dentata. Levels of the pro-inflammatory cytokine IL-1beta were reduced by 84%
      after treatment with SB239063 whereas the cytokines IL-6 and TNF-alpha were not
      affected. After 6 days, neurogenesis was significantly increased in the posterior
      periventricle. Based on these findings, our study shows that anti-inflammatory
      treatment with SB239063 reduces cell death, inflammation and microglia activation
      and, at high concentrations, enhances the oxygen-glucose deprivation-induced
      neurogenesis in the posterior periventricle.

PMID- 18638473
TI  - Effects of tamoxifen and raloxifene on normal human endometrial cells in an
      organotypic in vitro model.
AB  - The selective estrogen receptor modulator tamoxifen is widely used in breast
      cancer therapy though its use is associated with an elevated risk of endometrial
      carcinoma. An organotypic culture model was employed here to examine the effects
      of tamoxifen and raloxifene, a related compound with no known adverse uterine
      effects, on epithelial cells of the premenopausal human endometrium. Changes in
      the expression levels of the proliferation marker Ki67, and estrogen and
      progesterone receptors were evaluated. No change in the Ki67 index compared to
      untreated controls was detected in cultures exposed to tamoxifen or
      tamoxifen+estradiol. In response to tamoxifen, the level of progesterone receptor
      expressing organoids was shown to vary markedly between individual samples,
      whereas no change in estrogen receptor expression could be demonstrated. A
      significant decrease in Ki67 expression was observed in raloxifene-exposed
      cultures. Raloxifene or raloxifene+estradiol had no effect on progesterone
      receptor expression. The expression of estrogen receptor was markedly inhibited
      in response to raloxifene or raloxifene+estradiol in all but two samples
      displaying an intense estrogen receptor labelling. The present observations add
      to current clinical data on the respective estrogen receptor agonist and
      antagonist activities of tamoxifen and raloxifene on the human uterus by
      providing novel insights into the interindividual variation in cellular
      responses. Our organotypic model may have uses as an alternative to animal
      experimentation in preclinical screening of the endometrial effects of selective
      estrogen receptor modulators and may serve as a tool in personalized medicine by
      identifying patients with an increased risk of developing endometrial
      pathologies.

PMID- 18638474
TI  - Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in
      sensory neurons.
AB  - Dystonin/Bpag1 proteins are cytoskeletal linkers whose loss of function in mice
      results in a hereditary sensory neuropathy with a progressive loss of limb
      coordination starting in the second week of life. These mice, named dystonia
      musculorum (dt), succumb to the disease and die of unknown causes prior to sexual
      maturity. Previous evidence indicated that cytoskeletal defects in the axon are a
      primary cause of dt neurodegeneration. However, more recent data suggests that
      other factors may be equally important contributors to the disease process. In
      the present study, we demonstrate perikaryal defects in dorsal root ganglion
      (DRG) neurons at stages preceding the onset of loss of limb coordination in dt
      mice. Abnormalities include alterations in endoplasmic reticulum (ER) chaperone
      protein expression, indicative of an ER stress response. Dystonin in sensory
      neurons localized in association with the ER and nuclear envelope (NE). A fusion
      protein ofthe dystonin-a2 isoform, which harbors an N-terminal transmembrane
      domain, associated with and reorganized the ER in cell culture. This isoform also
      interacts with the NE protein nesprin-3alpha, but not nesprin-3beta. Defects in
      dt mice, as demonstrated here, may ultimately result in pathogenesis involving ER
      dysfunction and contribute significantly to the dt phenotype.

PMID- 18638475
TI  - Age-related synthesis of glucocorticoids in thymocytes.
AB  - Glucocorticoids (GCs) are primarily synthesized in the adrenal glands but an
      ectopic production has also been reported in the brain, the gastrointestinal
      tract and in thymic epithelial cells (TEC). Here we show that thymocytes express
      genes encoding for all enzymes required for de novo GC synthesis and produce the
      hormone as demonstrated by both a GC specific reporter assay and a corticosterone
      specific ELISA assay. Interestingly, GC synthesis is detectable in cells from
      young mice (4 weeks) and thereafter increases during aging (14-22 weeks) together
      with an increased gene expression of the rate-limiting enzymes StAR and CYP11A1.
      Hormone production occurred at a thymocyte differentiation stage characterized by
      being double positive for the CD4 and CD8 surface markers but was found to be
      unrelated to CD69 expression, a marker for thymocytes undergoing positive
      selection. No GC synthesis was found in resting or anti-CD3 activated CD4 and CD8
      positive T cells isolated from the spleen. Thymocyte-derived GC had an anti
      proliferative effect on a GR-transfected cell line and induced apoptosis in
      thymocytes. The age- and differentiation stage-related GC synthesis in thymocytes
      may play a role in the involution process that the thymus gland undergoes.

PMID- 18638476
TI  - Zinc-mediated feedback at the synaptic terminals of vertebrate photoreceptors.
AB  - There is mounting evidence that zinc release from glutamatergic nerve terminals
      serves as a neuromodulator at synaptic sites within the retina and CNS. However,
      it has not been possible to reliably measure the concentration of zinc co
      released with glutamate in the confines of the synaptic cleft. Thus, much of the
      evidence supporting this view derives from electrophysiological studies showing
      the modulatory effects of exogenous zinc on the membrane currents of ligand- and
      voltage-gated channels. In the present study, we took advantage of the unique
      properties of the glutamatergic photoreceptor terminal to demonstrate a feedback
      signal mediated by endogenous zinc at the synaptic sites from which it is
      discharged. Through its ability to block voltage-gated calcium channels in the
      photoreceptor terminal, zinc suppresses the radial dark current of the visual
      cell, and reduces its release of glutamate. It follows that chelation of
      extracellular zinc, e.g., with histidine, will lead to an increase both in the
      dark current and in the release of glutamate, changes that result in an
      enhancement of the light-evoked a-wave of the ERG and can account for the b-wave
      enhancement observed previously after zinc chelation when inner retinal responses
      were not blocked by aspartate.

PMID- 18638477
TI  - High frequency stimulation of the posterior hypothalamic nucleus restores
      movement and reinstates hippocampal-striatal theta coherence following
      haloperidol-induced catalepsy.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus has been used extensively
      in the treatment of Parkinson's disease. However, the efficacy of such treatments
      on bradykinesia/akinesia remains low. DBS of the posterior hypothalamic nucleus
      (PH) elicits spontaneous, non-stereotypical motor behaviours. We tested the
      hypothesis that PH stimulation could restore movement in animals made cataleptic
      by the D(2) receptor antagonist haloperidol. We further hypothesized that
      hippocampal-striatal neural synchrony may be important in the organization of
      motor behaviours. Animals chronically implanted with hippocampal and striatal
      recording electrodes and PH stimulating electrode were tested in open field,
      catalepsy and active avoidance paradigms. The degree of hippocampal-striatal
      theta (5-10 Hz) field coherence was assessed during baseline avoidance testing
      and following the administration of haloperidol. Haloperidol abolished movement
      in open field and active avoidance tasks and increased the latency to respond in
      the catalepsy test. Stimulation of the PH under haloperidol reversed catalepsy.
      Hippocampal-striatal theta coherence was high throughout the active avoidance
      task in control experiments but was greatly reduced under haloperidol. PH
      stimulation was able to reinstate the hippocampal-striatal theta coherence while
      restoring task-related behaviours. These results support the hypothesis that DBS
      of the PH could restore motor behaviours in rats made cataleptic with
      haloperidol, thus providing strong support for the PH as a promising candidate
      for DBS in the treatment of Parkinson's disease. Furthermore, the results support
      the view that hippocampal-striatal theta coherence may be important for the
      planning and execution of goal-oriented behaviors.

PMID- 18638478
TI  - Consequence of the loss of Sox2 in the developing brain of the mouse.
AB  - The transcription factor Sox2 is expressed at high levels in neural stem and
      progenitor cells. Here, we inactivated Sox2 specifically in the developing brain
      by using Cre-loxP system. Although mutant animals did not survive after birth,
      analysis of late gestation embryos revealed that loss of Sox2 causes enlargement
      of the lateral ventricles and a decrease in the number of neurosphere-forming
      cells. However, although their neurogenic potential is attenuated, Sox2-deficient
      neural stem cells retain their multipotency and self-renewal capacity. We found
      that expression level of Sox3 is elevated in Sox2 null developing brain, probably
      mitigating the effects of loss of Sox2.

PMID- 18638479
TI  - Urinary C-peptide as a method for monitoring body mass changes in captive bonobos
      (Pan paniscus).
AB  - In recent years methodological improvements have allowed for more precise
      estimates of nutrient intake in wild primates. However, estimates of energetic
      condition have remained relatively imprecise due to the difficulties of
      estimating digestive efficiency and energy expenditure in these animals. In the
      absence of a reliable intake-expenditure calculation, a method is needed that
      directly links changes in energetic condition, such as body mass, to
      physiological changes that can be detected via markers in body excretions such as
      urine or feces. One promising marker is C-peptide, a metabolic byproduct of
      insulin synthesis. Here we present the results of a food restriction experiment
      carried out in a group of captive bonobos (Pan paniscus). We measured changes in
      food availability and body mass and determined urinary C-peptide levels with the
      help of a time-resolved fluoroimmunoassay routinely used for measuring C-peptide
      in human blood. Urinary C-peptide levels decreased during a period of food
      restriction and increased again when food availability was continuously
      increased. During this refeeding phase an increase in body mass was significantly
      correlated with an increase in urinary C-peptide levels. Our results suggest that
      urinary C-peptide levels are an accurate indicator of individual energy balance.
      In conclusion, measuring C-peptide in urine is a promising method to quantify the
      energetic condition of wild apes.

PMID- 18638480
TI  - Physiologically induced color-pattern changes in butterfly wings: mechanistic and
      evolutionary implications.
AB  - A mechanistic understanding of the butterfly wing color-pattern determination can
      be facilitated by experimental pattern changes. Here I review physiologically
      induced color-pattern changes in nymphalid butterflies and their mechanistic and
      evolutionary implications. A type of color-pattern change can be elicited by
      elemental changes in size and position throughout the wing, as suggested by the
      nymphalid groundplan. These changes of pattern elements are bi-directional and bi
      sided dislocation toward or away from eyespot foci and in both proximal and
      distal sides of the foci. The peripheral elements are dislocated even in the
      eyespot-less compartments. Anterior spots are more severely modified, suggesting
      the existence of an anterior-posterior gradient. In one species, eyespots are
      transformed into white spots with remnant-like orange scales, and such patterns
      emerge even at the eyespot-less "imaginary" foci. A series of these color-pattern
      modifications probably reveal "snap-shots" of a dynamic morphogenic signal due to
      heterochronic uncoupling between the signaling and reception steps. The
      conventional gradient model can be revised to account for these observed color
      pattern changes.

PMID- 18638481
TI  - Structural basis for the interaction between the cytoplasmic domain of the
      hyaluronate receptor layilin and the talin F3 subdomain.
AB  - Talin is a large cytoskeletal protein that is involved in coupling the integrin
      family of cell adhesion molecules to the actin cytoskeleton, colocalising with
      the integrins in focal adhesions (FAs). However, at the leading edge of motile
      cells, talin colocalises with the hyaluronan receptor layilin in what are thought
      to be transient adhesions, some of which subsequently mature into more stable
      FAs. During this maturation process, layilin is replaced with integrins, which
      are highly clustered in FAs, where localised production of PI(4,5)P(2) by type 1
      phosphatidyl inositol phosphate kinase type 1gamma (PIPK1gamma) is thought to
      play a role in FA assembly. The talin FERM F3 subdomain binds both the integrin
      beta-subunit cytoplasmic domain and PIPK1gamma, and these interactions are
      understood in detail at the atomic level. The talin F3 domain also binds to short
      sequences in the layilin cytoplasmic domain, and here we report the structure of
      the talin/layilin complex, which shows that talin binds integrins, PIPK1gamma and
      layilin in similar although subtly different ways. Based on structure
      comparisons, we designed a set of talin F3 mutations that selectively affected
      the affinity of talin for its targets, as determined by stopped-flow fluorescence
      measurements. Such mutations will help to assess the importance of the
      interactions between talin and its various ligands in cell adhesion and
      migration.

PMID- 18638482
TI  - Agonist-induced conformational changes in bovine rhodopsin: insight into
      activation of G-protein-coupled receptors.
AB  - Activation of G-protein-coupled receptors (GPCRs) is initiated by conformational
      changes in the transmembrane (TM) helices and the intra- and extracellular loops
      induced by ligand binding. Understanding the conformational changes in GPCRs
      leading to activation is imperative in deciphering the role of these receptors in
      the pathology of diseases. Since the crystal structures of activated GPCRs are
      not yet available, computational methods and biophysical techniques have been
      used to predict the structures of GPCR active states. We have recently applied
      the computational method LITiCon to understand the ligand-induced conformational
      changes in beta(2)-adrenergic receptor by ligands of varied efficacies. Here we
      report a study of the conformational changes associated with the activation of
      bovine rhodopsin for which the crystal structure of the inactive state is known.
      Starting from the inactive (dark) state, we have predicted the TM conformational
      changes that are induced by the isomerization of 11-cis retinal to all-trans
      retinal leading to the fully activated state, metarhodopsin II. The predicted
      active state of rhodopsin satisfies all of the 30 known experimental distance
      constraints. The predicted model also correlates well with the experimentally
      observed conformational switches in rhodopsin and other class A GPCRs, namely,
      the breaking of the ionic lock between R135(3.50) at the intracellular end of TM3
      (part of the DRY motif) and E247(6.30) on TM6, and the rotamer toggle switch on
      W265(6.48) on TM6. We observe that the toggling of the W265(6.48) rotamer
      modulates the bend angle of TM6 around the conserved proline. The rotamer
      toggling is facilitated by the formation of a water wire connecting S298(7.45),
      W265(6.48) and H211(5.46). As a result, the intracellular ends of TMs 5 and 6
      move outward from the protein core, causing large conformational changes at the
      cytoplasmic interface. The predicted outward movements of TM5 and TM6 are in
      agreement with the recently published crystal structure of opsin, which is
      proposed to be close to the active-state structure. In the predicted active
      state, several residues in the intracellular loops, such as R69, V139(3.54),
      T229, Q237, Q239, S240, T243 and V250(6.33), become more water exposed compared
      to the inactive state. These residues may be involved in mediating the
      conformational signal from the receptor to the G protein. From mutagenesis
      studies, some of these residues, such as V139(3.54), T229 and V250(6.33), are
      already implicated in G-protein activation. The predicted active state also leads
      to the formation of new stabilizing interhelical hydrogen-bond contacts, such as
      those between W265(6.48) and H211(5.46) and E122(3.37) and C167(4.56). These
      hydrogen-bond contacts serve as potential conformational switches offering new
      opportunities for future experimental investigations. The calculated retinal
      binding energy surface shows that binding of an agonist makes the receptor
      dynamic and flexible and accessible to many conformations, while binding of an
      inverse agonist traps the receptor in the inactive state and makes the other
      conformations inaccessible.

PMID- 18638483
TI  - Catalytic cycle of human glutathione reductase near 1 A resolution.
AB  - Efficient enzyme catalysis depends on exquisite details of structure beyond those
      resolvable in typical medium- and high-resolution crystallographic analyses. Here
      we report synchrotron-based cryocrystallographic studies of natural substrate
      complexes of the flavoenzyme human glutathione reductase (GR) at nominal
      resolutions between 1.1 and 0.95 A that reveal new aspects of its mechanism.
      Compression in the active site causes overlapping van der Waals radii and
      distortion in the nicotinamide ring of the NADPH substrate, which enhances
      catalysis via stereoelectronic effects. The bound NADPH and redox-active
      disulfide are positioned optimally on opposite sides of the flavin for a 1,2
      addition across a flavin double bond. The new structures extend earlier
      observations to reveal that the redox-active disulfide loop in GR is an extreme
      case of sequential peptide bonds systematically deviating from planarity--a net
      deviation of 53 degrees across five residues. But this apparent strain is not a
      factor in catalysis, as it is present in both oxidized and reduced structures.
      Intriguingly, the flavin bond lengths in oxidized GR are intermediate between
      those expected for oxidized and reduced flavin, but we present evidence that this
      may not be due to the protein environment but instead due to partial synchrotron
      reduction of the flavin by the synchrotron beam. Finally, of more general
      relevance, we present evidence that the structures of synchrotron-reduced
      disulfide bonds cannot generally be used as reliable models for naturally reduced
      disulfide bonds.

PMID- 18638484
TI  - Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid
      bilayers.
AB  - Voltage-dependent K(+) (Kv) channels play key roles in shaping electrical
      signaling in both excitable and nonexcitable cells. These channels open and close
      in response to the voltage changes across the cell membrane. Many studies have
      been carried out in order to understand the voltage-sensing mechanism. Our
      laboratory recently determined the atomic structures of a mammalian Kv channel
      Kv1.2 and a mutant of Kv1.2 named the 'paddle chimera' channel, in which the
      voltage sensor paddle was transferred from Kv2.1 to Kv1.2. These two structures
      provide atomic descriptions of voltage-dependent channels with unprecedented
      clarity. Until now, the functional integrity of these two channels biosynthesized
      in yeast cells has not been assessed. Here, we report the electrophysiological
      and pharmacological properties of Kv1.2 and the paddle chimera channels in planar
      lipid bilayers. We demonstrate that Pichia yeast produce 'normally functioning'
      mammalian Kv channels with qualitatively similar features to the Shaker K(+)
      channel in the absence of the N-terminal inactivation gate and that the paddle
      chimera mutant channel functions as well as Kv1.2. We find, however, that in
      several respects, the Kv1.2 channel exhibits functional properties that are
      distinct from Kv1.2 channels reported in the literature.

PMID- 18638485
TI  - Rapid kinetic analysis of transcription elongation by Escherichia coli RNA
      polymerase.
AB  - Nucleotide incorporation during transcription by RNA polymerase is accompanied by
      pyrophosphate formation. Rapid release of pyrophosphate from the elongation
      complex at a rate consistent with productive transcription elongation occurs only
      in the presence of the correct next nucleotide for incorporation into the
      transcript.

PMID- 18638486
TI  - Structural determinants of the ADAM inhibition by TIMP-3: crystal structure of
      the TACE-N-TIMP-3 complex.
AB  - TIMP-3 (tissue inhibitor of metalloproteinases 3) is unique among the TIMP
      inhibitors, in that it effectively inhibits the TNF-alpha converting enzyme
      (TACE). In order to understand this selective capability of inhibition, we
      crystallized the complex formed by the catalytic domain of recombinant human TACE
      and the N-terminal domain of TIMP-3 (N-TIMP-3), and determined its molecular
      structure with X-ray data to 2.3 A resolution. The structure reveals that TIMP-3
      exhibits a fold similar to those of TIMP-1 and TIMP-2, and interacts through its
      functional binding edge, which consists of the N-terminal segment and other
      loops, with the active-site cleft of TACE in a manner similar to that of matrix
      metalloproteinases (MMPs). Therefore, the mechanism of TIMP-3 binding toward TACE
      is not fundamentally different from that previously elucidated for the MMPs. The
      Phe34 phenyl side chain situated at the tip of the relatively short sA-sB loop of
      TIMP-3 extends into a unique hydrophobic groove of the TACE surface, and two Leu
      residues in the adjacent sC-connector and sE-sF loops are tightly packed in the
      interface allowing favourable interactions, in agreement with predictions
      obtained by systematic mutations by Gillian Murphy's group. The combination of
      favourable functional epitopes together with a considerable flexibility renders
      TIMP-3 an efficient TACE inhibitor. This structure might provide means to design
      more efficient TIMP inhibitors of TACE.

PMID- 18638487
TI  - Ligand binding mode of GABAA receptor-associated protein.
AB  - The gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein is a
      versatile adaptor protein playing an important role in intracellular vesicle
      trafficking, particularly in neuronal cells. We present the X-ray structure of
      the soluble form of human GABA(A) receptor-associated protein complexed with a
      high-affinity synthetic peptide at 1.3 A resolution. The data shed light on the
      probable binding modes of key interaction partners, including the GABA(A)
      receptor and the cysteine protease Atg4. The resulting models provide a
      structural background for further investigation of the unique biological
      properties of this protein.

PMID- 18638488
TI  - Diffusion with memory in two cases of biological interest.
AB  - The complexity of a biological structure, such as membrane where the transport
      process may carry solid particles which may obstruct some of the pores,
      diminishing their size and making the permeability dependent on the local
      structure of the medium, suggests the introduction of a space-dependent diffusion
      constant. In this note, the profile concentration of diffusing solutes inside a
      cell membrane has been calculated on the basis of the Fick diffusion equation
      modified by introducing a memory formalism (diffusion with memory). This approach
      has been employed to describe the concentration profile inside the membrane when
      a sudden change of the concentration in the medium bathing one of its face is
      applied for a limited interval of time. A further application of the method
      concerns the so-called concentration boundary layer that occurs at the membrane
      aqueous medium interface, where the solute concentration depends, even at
      considerable depth, on the local structure of the interface. These profiles are
      compared to some recent experiments concerning the diffusion of ethanol in a
      layer close to a nephrophane membrane. This approach generalizes the diffusion
      models based on the Fick equation to more complex systems, where a space
      independent diffusion coefficient could be inappropriate to take into account the
      large variety of diffusion processes in biological systems.

PMID- 18638489
TI  - Evolution of cooperation and altruistic punishment when retaliation is possible.
AB  - Altruistic punishment is suggested to explain observed high levels of cooperation
      among non-kin related humans. However, laboratory experiments as well as
      ethnographic evidence suggest that people might retaliate if being punished, and
      that this reduces the level of cooperation. Building on existing models on the
      evolution of cooperation and altruistic punishment, we explore the consequences
      of the option of retaliation. We find that cooperation and altruistic punishment
      does not evolve with larger population levels if the option of retaliation is
      included.

PMID- 18638490
TI  - Involvement of multidrug resistance-associated protein 2 (ABCC2/Mrp2) in biliary
      excretion of micafungin in rats.
AB  - The drug transporter, multidrug resistance-associated protein 2 (ABCC2/Mrp2), is
      known to play important roles in excretion of various drugs. In the present
      study, we investigated whether Mrp2 is involved in the transport of micafungin, a
      newly developed antifungal agent. When Sprague-Dawley rats received an
      intravenous injection of micafungin (1 mg/kg) in combination with cyclosporine,
      the cyclosporine significantly delayed the disappearance of micafungin from
      plasma and decreased the systemic clearance and volume of distribution at steady
      state of micafungin to 54% and 65% of the corresponding control values,
      respectively. When Sprague-Dawley rats received a constant-rate infusion of
      micafungin, cyclosporine significantly decreased the steady-state biliary
      clearance of micafungin (approximately 80%). A significant decrease in the
      biliary clearance of micafungin (~60%) was observed in Eisai hyperbilirubinemic
      rats, which have a hereditary deficiency in Mrp2. The present findings at least
      suggest that Mrp2 is involved mainly in the hepatobiliary excretion of micafungin
      in rats.

PMID- 18638491
TI  - Method for inferring and extracting reliable genetic interactions from time
      series profile of gene expression.
AB  - Recent advances in technologies such as DNA microarrays have provided an
      abundance of gene expression data on the genomic scale. One of the most important
      projects in the post-genome-era is the systemic identification of gene expression
      networks. However, inferring internal gene expression structure from
      experimentally observed time-series data are an inverse problem. We have
      therefore developed a system for inferring network candidates based on
      experimental observations. Moreover, we have proposed an analytical method for
      extracting common core binomial genetic interactions from various network
      candidates. Common core binomial genetic interactions are reliable interactions
      with a higher possibility of existence, and are important for understanding the
      dynamic behavior of gene expression networks. Here, we discuss an efficient
      method for inferring genetic interactions that combines a Step-by-step strategy
      (Y. Maki, Y. Takahashi, Y. Arikawa, S. Watanabe, K. Aoshima, Y. Eguchi, T. Ueda,
      S. Aburatani, S. Kuhara, M. Okamoto, An integrated comprehensive workbench for
      inferring genetic networks: Voyagene, Journal of Bioinformatics and Computational
      Biology 2(3) (2004) 533.) with an analysis method for extracting common core
      binomial genetic interactions.

PMID- 18638492
TI  - Models for integrated pest control and their biological implications.
AB  - Successful integrated pest management (IPM) control programmes depend on many
      factors which include host-parasitoid ratios, starting densities, timings of
      parasitoid releases, dosages and timings of insecticide applications and levels
      of host-feeding and parasitism. Mathematical models can help us to clarify and
      predict the effects of such factors on the stability of host-parasitoid systems,
      which we illustrate here by extending the classical continuous and discrete host
      parasitoid models to include an IPM control programme. The results indicate that
      one of three control methods can maintain the host level below the economic
      threshold (ET) in relation to different ET levels, initial densities of host and
      parasitoid populations and host-parasitoid ratios. The effects of host intrinsic
      growth rate and parasitoid searching efficiency on host mean outbreak period can
      be calculated numerically from the models presented. The instantaneous pest
      killing rate of an insecticide application is also estimated from the models. The
      results imply that the modelling methods described can help in the design of
      appropriate control strategies and assist management decision-making. The results
      also indicate that a high initial density of parasitoids (such as in inundative
      releases) and high parasitoid inter-generational survival rates will lead to more
      frequent host outbreaks and, therefore, greater economic damage. The biological
      implications of this counter intuitive result are discussed.

PMID- 18638493
TI  - Networks, epidemics and vaccination through contact tracing.
AB  - We consider a (social) network whose structure can be represented by a simple
      random graph having a pre-specified degree distribution. A Markovian susceptible
      infectious-removed (SIR) epidemic model is defined on such a social graph. We
      then consider two real-time vaccination models for contact tracing during the
      early stages of an epidemic outbreak. The first model considers vaccination of
      each friend of an infectious individual (once identified) independently with
      probability p. The second model is related to the first model but also sets a
      bound on the maximum number an infectious individual can infect before being
      identified. Expressions are derived for the influence on the reproduction number
      of these vaccination models. We give some numerical examples and simulation
      results based on the Poisson and heavy-tail degree distributions where it is
      shown that the second vaccination model has a bigger advantage compared to the
      first model for the heavy-tail degree distribution.

PMID- 18638495
TI  - 2008 Eruptions in metabotropic glutamate receptors.

PMID- 18638494
TI  - Non-invasive imaging of barriers to drug delivery in tumors.
AB  - Solid tumors often develop high interstitial fluid pressure (IFP) as a result of
      increased water leakage and impaired lymphatic drainage, as well as changes in
      the extracellular matrix composition and elasticity. This high fluid pressure
      forms a barrier to drug delivery and hence, resistance to therapy. We have
      developed techniques based on contrast enhanced magnetic resonance imaging for
      mapping in tumors the vascular and transport parameters determining the delivery
      efficiency of blood borne substances. Sequential images are recorded during
      continuous infusion of a Gd-based contrast agent and analyzed according to a new
      physiological model, yielding maps of microvascular transfer constants, as well
      as outward convective interstitial transfer constants and steady state
      interstitial contrast agent concentrations both reflecting IFP distribution. We
      further demonstrated in non small cell human lung cancer xenografts the
      capability of our techniques to monitor in vivo collagenase induced increase in
      contrast agent delivery as a result of decreased IFP. These techniques can be
      applied to test drugs that affect angiogenesis and modulate interstitial fluid
      pressure and has the potential to be extended to cancer patients for assessing
      resistance to drug delivery.

PMID- 18638496
TI  - Combining physiological measures in the detection of concealed information.
AB  - Meta-analytic research has confirmed that skin conductance response (SCR)
      measures have high validity for the detection of concealed information.
      Furthermore, cumulating research has provided evidence for the validity of two
      other autonomic measures: Heart rate (HR) and Respiration Line Length (RLL). In
      the present report, we compared SCR detection efficiency with HR and RLL, and
      investigated whether HR and RLL provide incremental validity to electrodermal
      responses. Analyses were based on data from 7 different samples covering 275
      guilty and 53 innocent examinees. Results revealed that the area under the ROC
      curve was significantly higher for SCR than for HR and RLL. A weighted
      combination of these measures using a logistic regression model yielded slightly
      larger validity coefficients than the best single measure. These results proved
      to be stable across different protocols and various samples.

PMID- 18638497
TI  - Syntheses and structural study of bile acid amidoalcohols.
AB  - Preparation, structural and thermoanalytical characterization of fourteen N
      hydroxyalkyl 5beta-cholan-24-amides have been performed in this study. The
      utilized techniques include liquid state and CP-MAS 13C NMR spectroscopy,
      thermogravimetry, differential scanning calorimetry, and also powder and single
      crystal X-ray crystallography. The results were discussed and compared to each
      other and also to previous findings on similar compounds. One pure hydrate form
      was obtained. Six new single crystal structures were determined, including one
      hydrated chloroform solvate. Decomposition temperatures were found to correlate
      with the side chain length, and the number of the hydroxyl groups. The spatial
      direction of the groups in the steroid skeleton was also found to be relevant in
      predicting the thermal properties of bile acid amidoalcohols studied.

PMID- 18638498
TI  - Biomechanical properties of the cornea in high myopia.
AB  - PURPOSE: To determine corneal biomechanical properties in patients with high
      myopia. DESIGN: Observational study. METHODS: High myopia patients (n=45, age:
      37.0+/-12.6 years) with refractive errors of spherical equivalent (SE) greater
      than -9.00D were recruited in this study along with healthy subjects (n=90, age:
      33.7+/-12.4 years) with refractive errors of SE ranging from 0D to -3.00D. Only
      the right eye was studied. Central corneal thickness (CCT) was measured by
      optical coherence tomography (OCT). Metrics of corneal biomechanical properties,
      including corneal hysteresis (CH) and corneal resistance factor (CRF), were
      measured with the Ocular Response Analyzer (ORA). The ORA also determined the
      values of intraocular pressure (IOP(g)) and corneal compensated IOP (IOP(cc)).
      RESULTS: No significant differences of CCT and CRF were present between the two
      groups (P=.15 and 0.35 for CCT and CRF, respectively); however, CH in the high
      myope group was lower than that in the controls (P<.01). IOP(g) and IOP(cc) were
      both significantly higher in the high myopes compared to the controls. In both
      groups, there were significant correlations between CH and CCT and between CRF
      and CCT. CH was not significantly correlated with age in either the control group
      or the high myope group (P>.05). There was a significant correlation between CH
      and SE when the two groups were combined for analysis. CONCLUSION: CH, but not
      CRF, was significantly lower in high myopia patients compared to that in normal
      subjects. The results indicate that some compromised aspects of the biomechanical
      properties of cornea may exist in people with high myopia.

PMID- 18638499
TI  - Participation of the GABA/benzodiazepine receptor and the NO-cyclicGMP pathway in
      the "antinociceptive-like effects" of diazepam.
AB  - The mechanism of action underlying the "analgesic activity" of diazepam remains
      unclear. In this study, the possible participation of the GABA/benzodiazepine
      receptor and the nitric oxide-cyclic GMP (NO-cGMP) pathway was assessed utilizing
      the pain-induced functional impairment model in the rat (PIFIR). Nociception was
      induced by an intra-articular injection of 15% uric acid. Diazepam (1 and 2
      mg/kg, i.p.) reversed the dysfunction induced by uric acid. Flumazenil (10 mg/kg,
      i.p.), a GABA/benzodiazepine receptor antagonist, abolished the "antinociceptive
      like effect" of diazepam (at 2 mg/kg). The "antinociceptive-like effect" of
      diazepam (at 2 mg/kg) was antagonized by the non-selective nitric oxide synthase
      (NOS) inhibitor, Nomega-L-nitro-arginine methyl ester hydrochloride (L-NAME, 5
      mg/kg, s.c.) (but not by its inactive isomer), and by the selective neuronal NOS
      inhibitor, 7-nitroindazole (7-NI, 1 mg/kg, i.p). While, the NO precursor, l
      arginine (125 mg/kg, s.c.), but not d-arginine (125 mg/kg, s.c.), increased the
      "antinociceptive-like effect" of a non-effective dose of diazepam (1 mg/kg).
      Methylene blue (10 mg/kg, i.p.), a guanylate cyclase inhibitor, also prevented
      the "antinociceptive-like effect" of diazepam (at 2 mg/kg). These results suggest
      that the GABA/benzodiazepine receptor and the NO-cGMP pathway participate in the
      "antinociceptive-like effect" of diazepam.

PMID- 18638500
TI  - Protective effect of polysaccharides from morinda officinalis on bone loss in
      ovariectomized rats.
AB  - In order to examine the effect of polysaccharides from morinda officinalis (MOP)
      on bone quality of osteoporosis rats. The osteoporosis in rats was induced by
      ovariectomy, and MOP (100 or 300 mg/kg) was orally administrated once daily. The
      animals were assessed 30 days after the operation for bone mineral density, serum
      cytokines level and mineral element concentration. MOP administration in rats
      resulted in an increase in bone mineral density and mineral element
      concentration, a decrease in serum cytokines level, which indicated that MOP
      administration may play an important role in the development of osteoporosis.

PMID- 18638501
TI  - Intestinal intraepithelial NK and NKT cell ontogeny in Lewis rats.
AB  - Natural killer T (NKT) cells have been described in the liver and spleen of adult
      rats, but their presence and function in other tissues and in early life remains
      uncertain. This study was designed to determine the proportion of NK cells and
      NKT cells among small intestine intraepithelial (IE) lymphocytes in suckling rats
      and adult animals by flow cytometry. Very few intestinal IE-NKT cells (NKR-P1A+
      TCRalphabeta+) were present in adult rats ( approximately 1%), but a high
      proportion of this population was found during early life ( approximately 40% of
      IE lymphocytes in 9-day-old rats), with a marked age-decreasing pattern. Most of
      these cells presented the CD8alphabeta+ phenotype. Intestinal IE-NK cells (NKR
      P1A+ TCRalphabeta-) were also present in a relatively high proportion during the
      suckling period ( approximately 30% of IE lymphocytes). Thus, a predominance of
      both NK and NKT cell subpopulations in small intestine epithelium is
      characteristic in the early life of rats and may have a protective role during
      the suckling period.

PMID- 18638502
TI  - Three isoforms of complement properdin factor P in trout: cloning, expression,
      gene organization and constrained modeling.
AB  - Properdin is a plasma glycoprotein and the only known naturally occurring
      positive regulator of the complement system, stabilizing the alternative pathway
      convertase (C3bBb). In order to elucidate the molecular evolution of properdin
      factor P (pfc), here we report the cloning and characterization of three gene
      isoforms of properdin in rainbow trout (Oncorhynchus mykiss). The predicted
      polypeptide sequences of trout properdins pfc1, pfc2 and pfc3 (447, 449 and 447
      amino acids, respectively) share 78-90% identity to each other, showing the
      highest identity score (47%) with their zebrafish ortholog protein. The overall
      identity with human, mouse and xenopus properdin polypeptides is 44%, 42% and
      45%, respectively. The 'domain' architecture of trout properdins resembles that
      of the mammalian counterpart proteins, composed of six thrombospondin repeat type
      1 domains (TSR-1-TSR-6). TSR domains of the three trout properdin isoforms seem
      to adopt the folding pattern of human thrombospondin 1 TSP-1 domains, where each
      TSP-1 domain forms an antiparallel three-stranded structure that consists of
      alternative stacked layers of Trp and Arg residues from respective strands capped
      by disulfide bonds on each end. The trout pfc2 and pfc3 genes are arranged in
      nine and ten exons, respectively, which span approximately 3.5kb of the genome.
      In contrast to the expression profile of the properdin gene in mammals, liver is
      the main source of the trout properdin mRNA transcripts. In a phylogenetic
      analysis, trout pfc1, pfc2 and pfc3 genes are clustered with their orthologs from
      other teleost species. This is the first report of three separate genes coding
      for properdin factor P in a vertebrate species.

PMID- 18638503
TI  - Evaluation of chicken-origin (DF-1) and quail-origin (QT-6) fibroblast cell lines
      for replication of avian influenza viruses.
AB  - Avian influenza viruses (AIVs) are isolated routinely and propagated in specific
      pathogen free embryonated chicken eggs (ECE) and mammalian origin Madin-Darby
      Canine Kidney (MDCK) cell line. Continuous avian cell lines offer advantages for
      propagation of AIVs over MDCK cells because they maintain species specificity,
      and lower recurring costs compared to ECE. In this study, the characteristics of
      two avian fibroblast cell lines were evaluated, DF-1 (chicken-origin) and QT-6
      (quail-origin), and their ability to support the growth of AIVs (n=19) belonging
      to nine different hemagglutinin subtypes from a variety of avian species. The
      replication efficiency of the AIVs in QT-6 and DF-1 cells was comparable to those
      in primary chicken embryo fibroblast (CEF) and MDCK cells. Receptor distribution
      analysis demonstrated high prevalence of SA alpha2,3-gal linked receptors in QT-6
      and DF-1 cells which support a high growth of AIVs in these cell lines.
      Furthermore, the QT-6 and DF-1 cells supported high plaque-forming ability of
      representative highly pathogenic Eurasian H5N1 and H7N1 subtype AIVs. These two
      avian cell lines, especially QT-6 cells, also showed high transfection efficiency
      and could be useful for reverse genetics based rescue of AIVs. This study
      indicates that the DF-1 and QT-6 cell lines may be useful as a substitute for
      primary CEF and MDCK cells for AIV research in the areas of in vitro host range,
      molecular pathobiology and molecular genetics.

PMID- 18638504
TI  - DIVA diagnostic of Aujeszky's disease using an insect-derived virus glycoprotein
      E.
AB  - Commercial vaccines against Aujeszky's disease are mainly formulated using
      deleted versions of attenuated or inactivated Pseudorabies virus (PRV) particles
      lacking of the structural glycoprotein E (gE). Complementary diagnostic assays
      used to differentiate infected from vaccinated animals (DIVAs), are based on the
      detection of serum antibodies against gE. A recombinant version of the PRV gE
      protein was expressed in a baculovirus vector system in Trichoplusia ni insect
      larvae in order to obtain this diagnostic reagent for large scale diagnosis at
      reduced costs. A recombinant gE gene (gEr), lacking of signal peptide and
      transmembrane domains, was cloned into a modified baculovirus vector to allow
      glycosylation of the protein and its subsequent exportation to the extracellular
      space. Analysis by SDS-PAGE, Western-blotting and glycoprotein staining revealed
      that a glycosylated protein of the expected electrophoretic mobility was obtained
      in infected larvae. Time course experiments revealed that maximum expression
      levels were reached 72h post-infection using 10(4)pfu of the recombinant
      baculovirus (BACgEr) per inoculated larva. An indirect PRV gE-ELISA was developed
      using gEr as a coating antigen. A comparison between larvae-derived PRV gE-ELISA
      and two commercially available PRV diagnostic kits showed good correlation
      between assays and better sensitivity when testing certain sera pig samples using
      the gEr ELISA. More than 30,000 ELISA determinations could be performed from
      crude extracts obtained from a single larva infected with the recombinant
      baculovirus, indicating the feasibility of this strategy for inexpensive
      production of glycosylated antigens for PRV diagnosis.

PMID- 18638505
TI  - Site-specific effects of anosmia and cloacal gland anesthesia on Fos expression
      induced in male quail brain by sexual behavior.
AB  - In rats, expression of the immediate early gene, c-fos observed in the brain
      following male copulatory behavior relates mostly to the detection of olfactory
      information originating from the female and to somatosensory feedback from the
      penis. However, quail, like most birds, are generally considered to have a
      relatively poorly developed sense of smell. Furthermore, quail have no
      intromittent organ (e.g., penis). It is therefore intriguing that expression of
      male copulatory behavior induces in quail and rats a similar pattern of c-fos
      expression in the medial preoptic area (mPOA), bed nucleus of the stria
      terminalis (BSTM) and parts of the amygdala. We analyzed here by
      immunocytochemistry Fos expression in the mPOA/BSTM/amygdala of male quail that
      had been allowed to copulate with a female during standardized tests. Before
      these tests, some of the males had either their nostrils plugged, or their
      cloacal area anesthetized, or both. A control group was not exposed to females.
      These manipulations did not affect frequencies of male sexual behavior and all
      birds exposed to a female copulated normally. In the mPOA, the increased Fos
      expression induced by copulation was not affected by the cloacal gland anesthesia
      but was markedly reduced in subjects deprived of olfactory input. Both
      manipulations affected copulation-induced Fos expression in the BSTM. No change
      in Fos expression was observed in the amygdala. Thus immediate early gene
      expression in the mPOA and BSTM of quail is modulated at least in part by
      olfactory cues and/or somatosensory stimuli originating from the cloacal gland.
      Future work should specify the nature of these stimuli and their function in the
      expression of avian male sexual behavior.

PMID- 18638507
TI  - Cabergoline and pramipexole fail to modify already established dyskinesias in an
      animal model of parkinsonism.
AB  - Levodopa-induced dyskinesias are one of the major limiting side effects
      encountered in the treatment of Parkinson's disease. Dopamine agonists of the D2
      family are less prone to induce these abnormal involuntary movements (AIMs), and
      in some instances it has been proposed that they could counteract them once
      already established. As differences in the plasma half-life of a given DA agonist
      could be related with a greater or lesser propensity to induce or to counteract
      AIMs, we compared the effects of two D2 agonists (cabergoline and pramipexole)
      with different half-lives, and levodopa, at doses producing similar improvement
      in purposeful forelimb use, in rats with severe nigrostriatal lesion, previously
      sensitized to levodopa. The same therapeutic regime was subsequently used in
      pharmacologically naive rats. We found that: (i) prior induction of AIMs by
      levodopa administration primes rats for the occurrence of AIMs during mono
      therapy with pramipexole (but not with cabergoline); (ii) an intervening period
      of D2 agonist mono-therapy does not modify the severity of AIMs induced by
      subsequent mono-therapy with levodopa; iii. de novo treatment with D2 agonists is
      associated with a lower risk of AIMs (regardless of the severity of the lesion)
      and does not modify AIMs during subsequent mono-therapy with levodopa. An
      unexpected finding was that prior levodopa therapy sensitized rats to the
      therapeutic effects of D2 agonists given in mono-therapy. In summary, the use of
      the rat with nigrostriatal lesion to model relevant therapeutic conditions does
      not support that D2 agonists prevent the development of AIMs during subsequent
      levodopa mono-therapy or can revert the dysfunction underlying it.

PMID- 18638506
TI  - A delayed and chronic treatment regimen with the 5-HT1A receptor agonist 8-OH
      DPAT after cortical impact injury facilitates motor recovery and acquisition of
      spatial learning.
AB  - An early (i.e., 15min) single systemic administration of the 5-HT(1A) receptor
      agonist 8-OH-DPAT enhances behavioral recovery after experimental traumatic brain
      injury (TBI). However, acute administration of pharmacotherapies after TBI may be
      clinically challenging and thus the present study sought to investigate the
      potential efficacy of a delayed and chronic 8-OH-DPAT treatment regimen. Forty
      eight isoflurane-anesthetized adult male rats received either a controlled
      cortical impact or sham injury and beginning 24h later were administered 8-OH
      DPAT (0.1 or 0.5mg/kg) or saline vehicle (1.0mL/kg) intraperitoneally once daily
      until all behavioral assessments were completed. Neurobehavior was assessed by
      motor and cognitive tests on post-operative days 1-5 and 14-19, respectively. The
      lower dose of 8-OH-DPAT (0.1mg/kg) enhanced motor performance, acquisition of
      spatial learning, and memory retention vs. both the higher dose (0.5mg/kg) and
      vehicle treatment (p<0.05). These data replicate previous findings from our
      laboratory showing that 8-OH-DPAT improves neurobehavior after TBI, and extend
      those results by demonstrating that the benefits can be achieved even when
      treatment is withheld for 24h. A delayed and chronic treatment regimen may be
      more clinically feasible.

PMID- 18638508
TI  - Identification, expression and characterisation of a Babesia bovis hexose
      transporter.
AB  - Babesia are tick-transmitted haemoprotozoan parasites that infect cattle, with an
      estimated 500 million at risk worldwide. Here, two predicted hexose transporters
      (BboHT1 and 2) have been identified within the Babesia bovis genome. BboHT1,
      having 40% and 47% amino acid sequence similarity compared with the human (GLUT1)
      and Plasmodium falciparum (PfHT) hexose transporters, respectively, is the only
      one that could be characterised functionally after expression in Xenopus laevis
      oocytes. Radiotracer studies on BboHT1 showed that it is a saturable, Na(+)
      independent, stereo-specific hexose transporter, with a K(m) value for glucose of
      0.84+/-0.54 mM (mean+/-SEM). Using D-glucose analogues, hydroxyl positions at O-4
      and O-6 have been identified as important for ligand binding to BboHT1. D-glucose
      transport was inhibited maximally by cytochalasin B (50 microM). A long-chain O-3
      hexose derivative (compound 3361) that selectively inhibits PfHT also inhibited
      relatively potently BboHT1, with an apparent K(i) value of 4.1+/-0.9 microM
      (mean+/-SEM). Compound 3361 did not inhibit B. bovis proliferation in in vitro
      growth assays but inhibited invasion of glucose-depleted bovine erythrocytes.
      Taken together with results of inhibition studies with cytochalasin B and beta
      glucogallin, these data provide new insights into glucose metabolism of
      erythrocytic-stage Babesia infections.

PMID- 18638509
TI  - A proteomic approach to the identification of tegumental proteins of male and
      female Schistosoma bovis worms.
AB  - Schistosoma bovis, a parasite of ruminants, can live for years in the bloodstream
      in spite of the immune response of its host. The parasite tegument covers the
      entire surface of the worm and plays a key role in the host-parasite
      relationship. The parasite molecules involved in host immune response evasion
      mechanisms must be expressed on the tegument surface and are potential targets
      for immune or drug intervention. The purpose of the present work was to identify
      the tegumental proteomes of male and female S. bovis worms, in particular the
      proteins expressed on the outermost layers of the tegument structure. Adult worms
      of each sex were treated separately with trypsin in order to digest their
      tegumental proteins, after which the peptides released were analysed by LC-MS/MS
      for identification. This experimental approach afforded valuable information
      about the protein composition of the tegument of adult S. bovis worms. A range of
      tegumental proteins was identified, most of which had not been identified
      previously in this species. Although an absolute purification of the proteins
      expressed on the outermost layers of the tegument structure was not achieved, it
      is likely that present among the proteins identified are some of the molecules
      most closely associated with the tegument surface. Our study also suggests that
      there may be differences in the protein composition of the tegument of male and
      female schistosomes. Finally, the presence of actin and GAPDH on the surface of
      male and female worms and the presence of enolase exclusively on the surface of
      male worms were verified by confocal microscopy.

PMID- 18638510
TI  - An outbreak of acute hemorrhagic conjunctivitis (AHC) caused by coxsackievirus
      A24 variant in Pakistan.
AB  - Acute hemorrhagic conjunctivitis (AHC) is a self-limiting viral infection of the
      eyes but having epidemic potential. In winter 2004-2005, an outbreak of acute
      hemorrhagic conjunctivitis (AHC) occurred in Islamabad, Pakistan. The etiological
      agent was confirmed as coxsackievirus A24 variant (CA24v) by virus isolation and
      sequencing of a part of the VP1/VP3 gene. Phylogenetic analysis in VP1 region
      showed that Pakistan isolates has closest matches both in Asia and Europe while
      in VP1/VP3 region they were more closely related to Chinese strains, suggesting
      their common source in Asia which is constantly evolving to cause AHC outbreaks
      in susceptible hosts in different parts of the world.

PMID- 18638512
TI  - Structure and function of HCV IRES domains.
AB  - The HCV IRES is a highly structured RNA which mediates cap-independent
      translation initiation in higher eukaryotes. This function is encoded in
      conserved structural motifs in the two major domains of HCV and HCV-like IRESs,
      which play crucial and distinct roles along the initiation pathway. In this
      review, I discuss structural features of IRES domains and how these RNA motifs
      function as RNA-based initiation factors to form 48S initiation complexes and 80S
      ribosomes with only a subset of canonical, protein-based eukaryotic initiation
      factors.

PMID- 18638513
TI  - The influence of parents' dietary beliefs and behaviours on children's dietary
      beliefs and behaviours. The CYKIDS study.
AB  - We investigated the association between parental dietary beliefs and behaviours
      (DBB) and those of their children behaviours. Data were derived from a national
      cross-sectional study using multistage sampling design, among 1140 children (9-13
      years). Principal component analysis was employed to extract the main factors out
      of eight variables assessing children's dietary beliefs and behaviours (N=991);
      those eight factors were then regressed, on 16 dependent variables, describing
      different parental dietary beliefs and behaviours, adjusted for potential
      confounders. Three factors emerged as important in explaining the variance in
      children's dietary beliefs and behaviours: "guilty about eating" (factor 1),
      "concerned about own body weight" (factor 2) and "eating all my food" (factor 3).
      Children with types 1-3 behaviour: were 30% more likely to have parents who did
      not control what and how much their child ate, have parents who are 40% more
      likely to think that their child is overweight/obese and seem to have more
      availability of high fat foods, respectively. Breastfeeding was associated with
      the acquisition of positive dietary beliefs and behaviours by children,
      independently of child's age, gender, place of residence, socio-economic status,
      diet quality, and child's and parents' obesity status. We propose that parents
      are likely to exert their influence in shaping eating habits and subsequently
      obesity development in their children, by influencing their children's dietary
      beliefs and behaviours.

PMID- 18638511
TI  - Role of tRNA-like structures in controlling plant virus replication.
AB  - Transfer RNA-like structures (TLSs) that are sophisticated functional mimics of
      tRNAs are found at the 3'-termini of the genomes of a number of plant positive
      strand RNA viruses. Three natural aminoacylation identities are represented:
      valine, histidine, and tyrosine. Paralleling this variety in structure, the roles
      of TLSs vary widely between different viruses. For Turnip yellow mosaic virus,
      the TLS must be capable of valylation in order to support infectivity, major
      roles being the provision of translational enhancement and down-regulation of
      minus strand initiation. In contrast, valylation of the Peanut clump virus TLS is
      not essential. An intermediate situation seems to exist for Brome mosaic virus,
      whose RNAs 1 and 2, but not RNA 3, need to be capable of tyrosylation to support
      infectivity. Other known roles for certain TLSs include: (i) the recruitment of
      host CCA nucleotidyltransferase as a telomerase to maintain intact 3' CCA
      termini, (ii) involvement in the encapsidation of viral RNAs, and (iii)
      presentation of minus strand promoter elements for replicase recognition. In the
      latter role, the promoter elements reside within the TLS but are not functionally
      dependent on tRNA mimicry. The phylogenetic distribution of TLSs indicates that
      their evolutionary history includes frequent horizontal exchange, as has been
      observed for protein-coding regions of plant positive strand RNA viruses.

PMID- 18638514
TI  - Endocrine links between food reward and caloric homeostasis.
AB  - Both intrinsic and extrinsic (endocrine) inputs to the central nervous system
      (CNS) modulate motivation for feeding. Endocrine inputs such as insulin and
      leptin can have very rapid effects, but also the potential for chronic actions to
      decrease rewarding attributes of food. Future studies should elucidate the neural
      and cellular mechanisms which underlie these endocrine actions in the CNS.

PMID- 18638515
TI  - A new pentapeptide compound, PLNPK, ameliorates anti-glomerular basement membrane
      nephritis in Wistar rats.
AB  - PLNPK is a pentapeptide compound extracted from pig spleen with a Pro-Leu-Asn-Pro
      Lys molecular structure. The spleen is the biggest immune organ in the body, in
      which there are lots of immunocytes and immune molecules. Our pilot study showed
      that PLNPK could suppress the transformation and proliferation of T lymphocytes
      and the production of antibodies in mice. It is widely accepted that most types
      of glomerulonephritis are immunological diseases caused by the reaction of
      antigen and antibody. Both humoral immunity and cell-mediated immunity contribute
      to the progress of these diseases, and suppression of immunoreactions and
      inflammation is important to ameliorate nephritis. After the immunosuppressive
      effects of this compound were discovered, this study also examined whether PLNPK
      had beneficial effects on a rat model of glomerulonephritis. The results
      suggested PLNPK (200microg/kg/d and 400microg/kg/d) reduced urinary protein
      excretion, lessened the deposit of autoantibodies along the glomerular basement
      membrane (GBM), reduced formation of crescent and protein casts, and ameliorated
      glomerular fibrosis and GBM injury. After treatment with PLNPK (200microg/kg/d
      and 400microg/kg/d) for 7 days, macrophage infiltration in the glomeruli was
      markedly reduced. Our results suggest that PLNPK has a beneficial effect on rat
      anti-GBM nephritis.

PMID- 18638516
TI  - Blood pressure regulation and cardiac autonomic control in mice overexpressing
      alpha- and gamma-melanocyte stimulating hormone.
AB  - Melanocyte stimulating hormones (MSH) derived from pro-opiomelanocortin have been
      demonstrated to participate in the central regulation of cardiovascular
      functions. The aim of the present study was to elucidate the chronic effects of
      increased melanocortin activation on blood pressure regulation and autonomic
      nervous system function. We adapted telemetry to transgenic mice overexpressing
      alpha- and gamma-MSH and measured blood pressure, heart rate and locomotor
      activity, and analyzed heart rate variability (HRV) in the frequency-domain as
      well as baroreflex function by the sequence technique. Transgenic (MSH-OE) mice
      had increased systolic blood pressure but their heart rate was similar to wild
      type (WT) controls. The 24-h mean of systolic blood pressure was 132+/-7mmHg in
      MSH-OE and 113+/-4mmHg in WT mice. Locomotor activity was decreased in the MSH-OE
      mice. Furthermore, MSH-OE mice showed slower adaptation to mild environmental
      stress in terms of blood pressure changes. The low frequency (LF) power of HRV
      tended to be higher in MSH-OE mice compared to WT mice, without a difference in
      overall variability. The assessment of baroreflex function indicated enhanced
      baroreflex effectiveness and more frequent baroreflex operations in MSH-OE mice.
      Baseline heart rate, increased LF power of HRV and increased baroreflex activity
      may all reflect maintenance of baroreflex integrity and an increase in cardiac
      vagal activity to counteract the increased blood pressure. These results provide
      new evidence that long-term activation of the melanocortin system elevates blood
      pressure without increasing heart rate.

PMID- 18638517
TI  - Ginsenoside Rd prevents and rescues rat intestinal epithelial cells from
      irradiation-induced apoptosis.
AB  - Panax ginseng has been shown to have a protective effect for irradiated animals
      or cells. Ginsenosides are the most active components isolated from ginseng, and
      ginsenoside Rd has been identified as one of the effective compounds responsible
      for the pharmaceutical actions of ginseng. In the present study, we studied the
      molecular mechanisms for the radio-protective action of ginsenoside Rd in rat
      intestinal epithelial IEC-6 cells. Cells were irradiated with gamma-ray, and
      apoptosis was examined using Hoechst staining and Western blot analysis.
      Treatment with ginsenoside Rd before gamma-irradiation inhibited irradiation
      induced apoptosis in IEC-6 cells. Administration of Rd after irradiation also
      inhibited apoptosis in these cells. Irradiation of IEC-6 cells resulted in
      inactivation of Akt phosphorylation that was abrogated by Rd. On the other hand,
      irradiation activated phosphorylation of ERK1/2 but did not affect that of p38
      MAPK. Inhibition of Akt phosphorylation prevented the reduction of apoptosis by
      Rd following irradiation. Pretreatment with an inhibitor of the MEK pathway
      further decreased the number of apoptotic cells. Rd decreased the ratios of
      Bax/Bcl-2 and Bax/Bcl-xL, the levels of cytochrome c, and the cleaved form of
      caspase-3 in irradiated IEC-6 cells. Our results suggest that ginsenoside Rd
      protects and rescues rat intestinal epithelial cells from irradiation-induced
      apoptosis through a pathway requiring activation of PI3K/Akt, inactivation of
      MEK, and also inhibition of a mitochondria/caspase pathway.

PMID- 18638518
TI  - Individual and combined effects of ochratoxin A and citrinin on viability and DNA
      fragmentation in cultured Vero cells and on chromosome aberrations in mice bone
      marrow cells.
AB  - Ochratoxin A (OTA) and citrinin (CTN) are two common contaminant mycotoxins which
      can occur jointly in a wide range of food commodities. Both mycotoxins have
      several toxic effects but share a significant nephrotoxic and carcinogenic
      potential since OTA and CTN were reported to be responsible for naturally
      occurring human and animal kidney diseases and tumors. Considering the
      concomitant production of OTA and CTN, it is very likely that humans and animals
      are always exposed to the mixture rather than to individual compounds. Therefore,
      the aim of the present study was to investigate, in vivo and in vitro, whether
      DNA damage is enhanced by combination of both mycotoxins as compared to their
      effect separately. To this end, we have assessed their effects individually or
      combined on cell proliferation and DNA fragmentation in cultured Vero cells and
      in vivo by monitoring the induction of chromosome aberrations. Our results
      clearly showed that cultured renal cells respond to OTA and CTN exposure by a
      moderate and weak inhibition of cell proliferation, respectively. However, when
      combined, they exert a significant increase in inhibition of cell viability.
      Similar results were found for the investigated genotoxicity endpoints (DNA
      fragmentation and chromosome aberrations). Altogether, our study showed that OTA
      and CTN combination effects are clearly synergistic. The synergistic induction of
      DNA damage observed with OTA and CTN taken concomitantly could be relevant to
      explain the molecular basis of the renal diseases and tumorogenesis induced by
      naturally occurring mycotoxins.

PMID- 18638519
TI  - A neural circuit model for changing the amount of information maintained in short
      term memory depending on stimuli relationships.
AB  - We propose a neural circuit model of changes in amount of information maintained
      in short-term memory depending on stimuli relationships. The relationships
      between stimuli are represented by the synchronous firings of overlapping
      neuronal groups for semantically related stimuli and the excitatory mutual
      connections for semantically unrelated but simultaneously presented stimuli. We
      conduct computer simulations to confirm our proposed neural circuit model. The
      resultant numbers of stored informational input patterns are almost consistent
      with the maximum numbers in the psychological experiments for both semantically
      related and unrelated stimuli. This agreement with the psychological experiments
      suggests that the structure and informational representation of the proposed
      model are appropriate.

PMID- 18638520
TI  - Circadian rhythm drives the responsiveness of leptin-mediated hypothalamic
      pathway of cholecystokinin-8.
AB  - Cholecystokinin (CCK) and leptin act coordinately in the brain to regulate food
      intake and energy balance. Recently we have reported that CCK enhances the
      permeability of brain barriers to leptin and we have proposed that CCK enhances
      energy expenditure in rats by activating in the hypothalamus the janus
      kinase/signal transducer and activator of transcription (JAK/STAT) signalling
      pathway, which is coupled to leptin receptors. Because plasma leptin
      concentration follows a circadian rhythm (plasma leptin concentration rise
      maximal values during the night, after rats start eating), we have hypothesized
      that the interaction between leptin and CCK should be more intense in animals
      receiving CCK during the night, i.e., during periods of positive energy balance.
      In order to further characterize the physiological relevance of the interplay
      between leptin and CCK we have compared the effect of diurnal vs. nocturnal
      administration of the C-terminal octapeptide of CCK (CCK-8) on (i) body weight
      and food intake, and (ii) STAT3 activation, by analyzing phosphorylated STAT3
      (pSTAT3) immunostaining within the arcuate nucleus of the hypothalamus. Our
      results show that CCK decreases body weight and food intake only after p.m.
      administration. Accordingly pSTAT3 immunostaining within the hypothalamus was
      more intense in p.m. than in a.m.-treated animals. These data suggest that the
      effect of CCK on leptin pathways follows a circadian rhythm linked to the energy
      balance status and gives further support to the interaction between leptin and
      CCK.

PMID- 18638521
TI  - Expression and functional role of potassium-chloride cotransporters (KCC) in
      astrocytes and C6 glioma cells.
AB  - Brain edema formation following brain injury is a serious but still poorly
      treatable medical condition. The understanding of volume regulation in
      astrocytes, the main cells involved in the formation of cytotoxic brain edema, is
      key for the development of novel treatment strategies. This study investigates
      the role of potassium-chloride cotransporters (KCC) for cell volume regulation in
      glial cells. PCR revealed the expression of KCC isoforms in a glial cell line
      (C6) and primary cultured astrocytes. Specific inhibition of KCCs caused glial
      cell swelling and resulted in a complete inhibition of regulatory volume decrease
      upon hypotonic medium-induced cell swelling. Therefore, our results show that
      KCCs play an important role in the maintenance and regulation of cell volume in
      astrocytes.

PMID- 18638522
TI  - Synesthetic congruency modulates the temporal ventriloquism effect.
AB  - People sometimes find it easier to judge the temporal order in which two visual
      stimuli have been presented if one tone is presented before the first visual
      stimulus and a second tone is presented after the second visual stimulus. This
      enhancement of people's visual temporal sensitivity has been attributed to the
      temporal ventriloquism of the visual stimuli toward the temporally proximate
      sounds, resulting in an expansion of the perceived interval between the two
      visual events. In the present study, we demonstrate that the synesthetic
      congruency between the auditory and visual stimuli (in particular, between the
      relative pitch of the sounds and the relative size of the visual stimuli) can
      modulate the magnitude of this multisensory integration effect: The auditory
      capture of vision is larger for pairs of auditory and visual stimuli that are
      synesthetically congruent than for pairs of stimuli that are synesthetically
      incongruent, as reflected by participants' increased sensitivity in
      discriminating the temporal order of the visual stimuli. These results provide
      the first evidence that multisensory temporal integration can be affected by the
      synesthetic congruency between the auditory and visual stimuli that happen to be
      presented.

PMID- 18638523
TI  - Balance recovery from a forward fall: developmental aspects of sensorimotor
      organization and the role of supraspinal control.
AB  - We used the forward fall paradigm to test two hypotheses namely, that a
      supraspinal long-loop neural pathway is involved in the compensatory response,
      and secondly that the neural circuits underlying the performance of a balance
      challenging task that requires the sequencing of several motor programs
      (compensatory reactions and stepping to recover balance) matures late in
      childhood. The first hypothesis was supported by the findings that the responses
      occurred earlier when the triggering signal was moved from the abdominal up to
      the chest level. The time required to react to the triggering signal within the
      supraspinal structures was also longer in children. The second hypothesis was
      verified by the observation of persisting soleus-tibialis coactivation in
      children up to 14 years old in three experimental conditions: unexpected release
      of the fall, voluntary release of the fall and longitudinal testing. These
      results suggest that the central processes involved in sequencing the postural
      responses do not mature until mid-adolescence. The maturation continues
      throughout childhood, with progressive emphasis on the central long- rather than
      short-latency pathways.

PMID- 18638524
TI  - Effects of N-terminal fragments of beta-endorphin on feeding in chicks.
AB  - It is known that N-terminal fragments of beta-endorphin have biological
      activities, such as an antagonism effect of beta-endorphin (1-31) on the
      secretion of hormones or thermoregulation in mammals. We studied the effects of
      the N-terminal fragments on feeding behavior in male broiler chicks.
      Intracerebroventricular administration of beta-endorphin (1-27) (0.4nmol)
      stimulated feeding behavior compared with saline control during the 60-min
      experimental period. beta-Endorphin (1-17) (2.0nmol) also increased food intake
      at 30min postinjection. Co-injection of either beta-endorphin (1-27) or (1-17)
      was effective in reducing full-length beta-endorphin-induced feeding in chicks.
      These data suggest that the N-terminal fragments of beta-endorphin act as a
      partial agonist, and may regulate the activity of the central opioidergic system
      in chicks.

PMID- 18638525
TI  - Distinct regulation of brain-derived neurotrophic factor and noradrenaline in
      S100B knockout mice.
AB  - The mainly glia-derived protein S100B has been shown to be involved in the
      pathophysiology of diseases such as neurodegenerative diseases, schizophrenia or
      depression. These diseases go along with distinct changes of cerebral
      neurotransmitters and neurotrophic factors. Few and partly inconsistent data
      exist on the influence of cerebral S100B protein levels on different
      neurotransmitters. Therefore we investigated levels of serotonin (5-HT) and its
      metabolite 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA), dopamine
      (DA), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in
      the hippocampus, frontal cortex and residual neocortex in S100B knock out (S100B
      KO) mice compared to wildtype controls. There was a significant increase of
      hippocampal BDNF (+53%) and a decrease of hippocampal (-12%) and residual
      neocortical (-15%) NA in 10-month-old S100B KO mice compared to wildtype mice
      whereas the other mediators investigated did not show genotype-dependent changes.
      The increased hippocampal BDNF may represent an endogenous attempt to compensate
      trophic effects of S100B protein especially on serotonergic neurons, which have
      been shown to be unaffected in S100B KO mice previously. As referred to changes
      in NA levels functional studies are warranted to elucidate the link between S100B
      protein and the noradrenergic metabolism.

PMID- 18638526
TI  - Sleep-deprivation enhances in adult rats the antagonistic effects of pilocarpine
      on cortical spreading depression: a dose-response study.
AB  - Conditions that facilitate epilepsy, such as sleep deprivation or the cholinergic
      muscarinic agonist pilocarpine (PILO), have been experimentally studied, as they
      are relevant for brain excitability control and could help in understanding the
      development of epilepsy in humans. In this work, following to 72h deprivation (D)
      of sleep by the water tank technique, adult Wistar rats were anesthetized with a
      1g/kg urethane+40mg/kg chloralose mixture and cortical spreading depression (CSD)
      was recorded for a 1-2h period in the parietal surface. CSD propagation velocity
      was calculated based on the time spent for a CSD-wave to pass the interelectrode
      distance. After this "baseline" recording, D-animals were divided in three groups
      and respectively injected with 45, 95 and 190mg/kg of PILO, i.p., and the CSD
      recording continued for two more hours. Three groups of non-deprived (ND) rats
      were also injected with the three doses of PILO and studied regarding CSD
      features. D-animals presented higher baseline CSD velocities than the
      corresponding ND-controls, confirming previous observations that D-condition
      facilitates CSD propagation. After PILO, the ECoG amplitudes were markedly and
      lastingly reduced in all animals, at the three doses used. In the groups treated
      with 95 and 190mg/kg PILO, the CSD velocity of propagation significantly (P<0.05)
      decreased, and the incidence of PILO-associated CSD-propagation failure increased
      in the D rats, but not in the ND rats, as compared with the pre-drug values. The
      data suggest the existence of one or more cholinergic, muscarinic-mediated
      antagonistic processes influencing CSD, which are dose-dependent and are
      modulated by sleep-deprivation.

PMID- 18638527
TI  - Novel effects of Nelumbo nucifera rhizome extract on memory and neurogenesis in
      the dentate gyrus of the rat hippocampus.
AB  - Memory enhancement is a matter of concern in general, and in particular to people
      suffering from cognitive dysfunction. In this study, we investigated the effect
      of Nelumbo nucifera rhizome extract on learning and memory function. A step
      through passive avoidance test was performed with Wistar rats. In addition,
      immunohistochemistry was used to investigate cell proliferation and
      differentiation in the dentate gyrus of the hippocampus. The methanol extract of
      N. nucifera rhizome (MNR) resulted in significant improvements of memory
      functions and neurogenesis in the dentate gyrus. In the passive avoidance test,
      the retention time of MNR-treated rats was significantly longer than that of
      controls. Immunohistochemical analyses using BrdU, Ki-67, and DCX showed
      significantly increased cell proliferation and cell differentiation in the
      dentate gyrus. These results suggest that N. nucifera rhizome extract may improve
      learning and memory with enhancing neurogenesis in the DG of the hippocampus.

PMID- 18638528
TI  - Lack of evidence for association of a UCH-L1 S18Y polymorphism with Parkinson's
      disease in a Han-Chinese population.
AB  - Mutation in UCH-L1 has been reported as a rare cause of autosomal dominant
      Parkinson's disease (PD). A S18Y polymorphism in the same gene has been
      associated with sporadic PD. We investigated the frequency of this polymorphism
      among the Han-Chinese ethnic population in a case-control study. A total of 600
      patients with PD and 334 unrelated healthy controls were genotyped using PCR
      restriction fragment length polymorphism analysis. We did not observe any
      difference in allele or genotype frequencies between the cases and the controls
      (P>0.05). Our results do not support a role for this variant in sporadic PD.

PMID- 18638529
TI  - Possible involvement of cathepsin B released by microglia in methylmercury
      induced cerebellar pathological changes in the adult rat.
AB  - There is increasing evidence that cathepsin B (CB), a lysosomal cysteine
      protease, is one of the toxic molecules that are secreted by activated microglia.
      We herein provide evidence that CB released by activated microglia may play a
      role in the methylmercury (MeHg)-induced pathological changes observed in the
      cerebellum of the adult rat. Pathological changes tended to progress slowly after
      treatment with MeHg (5 mg/kg) for 12 consecutive days. At 5 days after the final
      treatment of MeHg, there was a mild pyknotic change of the granule cells, whereas
      a marked accumulation of activated microglia was observed in the granule cell
      layer of the lingual and central lobe. At 8 days after the final treatment,
      intense pyknotic changes of the granule cells and the accumulation of activated
      microglia were observed throughout the cerebellar vermis. CB first significantly
      increased at 3 days after the final treatment of MeHg as the mature form. CB
      mainly increased in activated microglia which accumulated in the granule cell
      layer. The coadministration of CA074, an irreversible CB inhibitor, with MeHg
      significantly reduced the severity of pyknotic changes of the granule cells.
      Furthermore, primary cultured microglia secreted the mature CB in the culture
      medium following cellular activation. These observations strongly suggest that CB
      secreted by activated microglia is thus closely associated with the MeHg-induced
      severe pyknotic changes of the cerebellar granule cells. The treatment of CA074
      could be a potentially effective therapeutic intervention to prevent the
      pathological changes in the cerebellum caused by ingestion of MeHg-contaminated
      food.

PMID- 18638530
TI  - The morphological changes of pyramidal and spiny stellate cells in the primary
      visual cortex of chronic morphine treated cats.
AB  - Morphine exposure may have a negative effect on the receptive field properties of
      neurons in primary visual cortex of cats. The present experiment used
      morphological methods in order to investigate whether chronic morphine treatment
      also affects dendritic characters of these neurons. According to the Sholl
      analysis and dendritic branch order analysis, we obtained the dendritic length
      and calculated the spine density on dendrites of the pyramidal neurons in layer
      III and the spiny stellate neurons in layer IV. The results showed that morphine
      exposure induced significant decreases in the total dendritic length and spine
      density on both pyramidal and spiny stellate neurons. The further branch order
      analysis revealed that spine density was decreased at every (first to fourth)
      branch order of dendrites of pyramidal and spiny stellate neurons. Decrease in
      dendritic length of the pyramidal neurons was observed only at the fourth branch
      order, while the spiny stellate neurons had shorter dendrite at the second and
      third branch order. These findings may underlie the degradation of receptive
      field properties of the primary visual cortex neurons following chronic morphine
      exposure.

PMID- 18638531
TI  - Dynamic and stable histone H3 methylation patterns at the Arabidopsis FLC and AP1
      loci.
AB  - Mechanisms that chemically modify nucleosomes leading to inheritable activation
      or repression of pertinent genes are defined as epigenetic. H3K4me3 and H3K27me3
      are interpreted as 'activating' and 'silencing' marks, respectively. Here, we
      demonstrate that even for related genes neither modification, alone, could serve
      as an indicator of expression status: despite being members of the same gene
      family selectively activated by ATX1, FLC and AP1 nucleosomes may be similarly
      decorated but, also, surprisingly different. 'Activating' H3K4me3 and 'silencing'
      H3K27me3 modifications co-exist at 5'-end nucleosomes of transcriptionally active
      FLC-gene, while highly transcribed AP1 displays neither of the two marks. The
      results suggest that distinct mechanisms 'read' and operate at each locus. In a
      remarkable contrast, H3K4me3-H3K27me3 profiles at downstream FLC and AP1 gene
      sequences remain unchanged and transmitted as stable marks throughout
      development. We propose that H3K4me3 and H3K27me3 produce a distinct bi-modular
      'syllable' in the histone 'code' conveying different meaning on specific genes.
      Evidence that certain chromatin modifications might be common for active or non
      active genome regions but, also, that the same histone signs might have gene
      specific 'meaning', as reported here, might be critically important for large
      scale genome analyses. ATX1 and CLF encode enzyme activities involved in
      establishing the H3K4me3 and H3K27me3 marks, respectively. The potential
      involvement of ATX1 and CLF in generating the dual H3K4me3 and H3K27me3 marks on
      FLC and AP1 nucleosomes was investigated.

PMID- 18638532
TI  - Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral
      administration: interaction with the transporters on Caco-2 cells.
AB  - In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after
      oral administration was evaluated in rats. Stability of the prodrugs, L-alanine
      ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV
      (EACV) and L-valine-ACV (VACV) was evaluated in various tissues. Interaction of
      these prodrugs with the transporters on Caco-2 cells was studied. In vivo
      systemic bioavailability of these prodrugs upon oral administration was evaluated
      in jugular vein cannulated rats. The amino acid ester prodrugs showed affinity
      towards various amino acid transporters as well as the peptide transporter on the
      Caco-2 cells. In terms of stability, EACV was most enzymatically stable compared
      to other prodrugs especially in liver homogenate. In oral absorption studies, ACV
      and AACV showed high terminal elimination rate constants (lambda(z)). SACV and
      VACV exhibited approximately five-fold increase in area under the curve (AUC)
      values relative to ACV (p<0.05). C(max(T)) (maximum concentration) of SACV was
      observed to be 39+/-22 microM in plasma which is 2 times better than VACV and 15
      times better than ACV. C(last(T)) (concentration at the last time point) of SACV
      was observed to be 0.18+/-0.06 microM in plasma which is two times better than
      VACV and three times better than ACV. Amino acid ester prodrugs of ACV were
      absorbed at varying amounts (C(max)) and eliminated at varying rates (lambda(z))
      thereby leading to varying extents (AUC). The amino acid ester prodrug SACV owing
      to its enhanced stability, higher AUC and better concentration at last time point
      seems to be a promising candidate for the oral treatment of herpes infections.

PMID- 18638533
TI  - South African traditional medicinal plant trade-Challenges in regulating quality,
      safety and efficacy.
AB  - Based on the long history of medicinal plant use, users of traditional medicines
      accept that they are safe for human consumption. However, the absence of
      regulation of the medicinal plant trade in aspects such as collection, processing
      and storage provides no such guarantee. Environmental pollution,
      misidentification and adulteration provides further grounds for concern. The
      potential adverse effects of South African traditional medicines are not well
      documented. There are only a few investigations of mutagenic properties and heavy
      metal contamination. In the absence of regulatory controls, the safety and
      quality of medicinal plants vary considerably. The current comprehension and
      future challenges regarding quality, safety and efficacy of South African
      traditional medicine are discussed.

PMID- 18638534
TI  - Novel xanthones from Securidaca longepedunculata with activity against erectile
      dysfunction.
AB  - AIM OF STUDY: Securidaca longepedunculata is used in the treatment of erectile
      dysfunction in South Africa. The aim of the study was to isolate and identify the
      active constituents and to determine their activity in the relaxation of corpus
      cavernosal smooth muscle. MATERIALS AND METHODS: Bioassay guided isolation of the
      bioactive compounds using a smooth muscle relaxation bioassay and structural
      elucidation was carried out using different spectroscopic techniques including 2D
      NMR. RESULTS: Two new xanthones were isolated; one of them showed potent activity
      to relax the corpus cavernosal smooth muscle by 97 % in comparison to sildenafil
      (Viagra) at 1.8 x 10(-5) mg/ml. CONCLUSIONS: S. longepedunculata's xanthones
      stimulate the relaxation of corpus cavenosum smooth muscle, which supports the
      traditional use of its root bark.

PMID- 18638535
TI  - Bioassay-guided isolation of anti-inflammatory and antinociceptive principles
      from a folk remedy, Rhododendron ponticum L. leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron ponticum L. (Ericaceae) is used for
      the treatment of inflammatory diseases and to alleviate rheumatic pain and
      against toothache in Turkish traditional medicine. AIM OF THE STUDY: To evaluate
      the anti-inflammatory and antinociceptive effects of Rhododendron ponticum leaves
      using in vivo models, and isolation and chemical characterization of the
      biologically active constituents through bioassay-guided fractionation
      procedures. MATERIAL AND METHODS: Carrageenan-induced hind paw edema model was
      used for anti-inflammatory activity and p-benzoquinone induced abdominal
      contractions model for the antinociceptive activity assessment. RESULTS: The
      ethylacetate fraction displayed marked anti-inflammatory (28.4-40.7% inhibition)
      and antinociceptive (50.7% inhibition) effects as compared to reference
      compounds. Through bioassay-guided fractionation and isolation procedures
      flavonol glycosides [a mixture of hyperoside and isoquercitrin (1) and quercitrin
      (2)] along with one flavanone glycoside [6-C-glycosylnaringenin (3)] were
      isolated as the active ingredients of ethylacetate extract against carrageenan
      induced edema and p-benzoquinone-induced writhes and their structures were
      elucidated by spectral techniques. 1 and 2 also showed a significant anti
      inflammatory activity against 12-O-tetradecanoyl-13-acetate (TPA)- induced mouse
      ear edema model. CONCLUSION: Results of the present study supported the
      utilization of the plant in Turkish folk medicine and revealed that flavones are
      the major anti-inflammatory and antinociceptive principles of the leaves.

PMID- 18638536
TI  - Antibacterial, antioxidant and fibroblast growth stimulation of aqueous extracts
      of Ficus asperifolia Miq. and Gossypium arboreum L., wound-healing plants of
      Ghana.
AB  - AIM OF THE STUDY: Use of in vitro tests to search for relevant activities in bark
      of Ficus asperifolia Miq. and leaves of Gossypium arboreum L., used in Ghana for
      wound healing. MATERIALS AND METHODS: Aqueous extracts of the relevant parts of
      the two species were tested for antibacterial activity against Staphylococcus
      aureus, Bacillus subtilis, Micrococcus flavus, Escherichia coli, Pseudomonas
      aeruginosa and resistant strains of Staphylococcus aureus SA1199B, RN4220 and
      XU212. The effects of the plants on fibroblast growth stimulation as well as
      antioxidant protective effect against hydrogen peroxide induced damage in the
      same cell line were also studied. RESULTS: The extracts of Gossypium arboreum and
      Ficus asperifolia had weak antibacterial action against all bacteria tested. The
      extracts of the two plants had significant (p<0.001) effects on the growth of
      human dermal fibroblast at 50 microg/ml and lower. They also significantly
      protected fibroblast cells against oxidative damage at doses up to 50 microg/ml.
      Gossypium arboreum leaf extract displayed the higher activity. CONCLUSION: The
      stimulatory effect on fibroblast growth and protection against peroxide-induced
      oxidative damage give some support to the traditional use of these two plants as
      wound-healing agents.

PMID- 18638537
TI  - In vitro and in vivo trypanocidal effect of lipophilic extracts of medicinal
      plants from Mali and Burkina Faso.
AB  - AIM OF THE STUDY: To determine the in vitro and in vivo antitrypanosomal activity
      of extracts of traditionally used plants. MATERIALS AND METHODS: 47
      dichloromethane extracts were tested in vitro in the Long-term Viability Assay
      (LtVA) on Trypanosoma brucei brucei. The most active ones were also tested in
      vivo using a standardised mouse test. RESULTS: 13 extracts (28%) were active in
      vitro with MIC-values < or = 100 microg/ml, 6 extracts showed MIC-values < or =
      50 microg/ml. The root extract of Securidaca longepedunculata Fresen.
      (Polygalaceae) and the leaf extract of Guiera senegalensis J. F. Gmel.
      (Combretaceae) were able to reduce parasitaemia in mice, experimentally infected
      with Trypanosoma brucei brucei by 48 and 42% at the dose of 150 mg/kg b.w.
      intraperitoneally, two times daily for 3 days. The extract of Acacia nilotica
      Delile (Mimosaceae) stem bark showed immunosuppressive effect in vivo.
      CONCLUSION: The results confirm an effect of the ethnobotanically used plants.
      Further investigation is needed to optimize the effectiveness of the extracts.

PMID- 18638538
TI  - Linking sirtuins, IGF-I signaling, and starvation.
AB  - Our studies in yeast have shown that the down-regulation of major signal
      transduction mediators increases stress resistance and causes an up to 10 fold
      chronological life span extension. Whereas other laboratories have proposed that
      sirtuins (Sir2 and its homologs), a family of conserved proteins which are NAD(+)
      dependent histone deacetylases, can extend longevity in various model organisms,
      we propose that one sirtuin, i.e., Sir2, can also accelerate cellular aging and
      death. In Saccharomyces cerevisiae (yeast), the deletion of Sir2 increases DNA
      damage but in combination with longevity mutations in principal intracellular
      signal transduction mediators, or in combination with calorie restriction it
      causes a further increase in the chronological lifespan as well as an increase in
      the stress resistance and a major reduction in age-dependent genomic instability.
      Our recent results also provide evidence for a role of the mammalian Sir2
      ortholog SirT1 in the activation of a highly conserved neuronal pathway and in
      the sensitization of neurons to oxidative damage. However, the mean lifespan of
      the SirT1(+/-) mice is not different from that of wild type animals, and the
      survival of SirT1(-/-) mice was reduced under both normal and calorie restricted
      conditions. Here, I review the studies linking SirT1, IGF-I signaling and
      starvation in various model organisms with a focus on the post-mitotic cells,
      which indicate that sirtuins can play both protective and pro-aging roles.

PMID- 18638539
TI  - Modest alterations in patterns of motor neuron dendrite morphology in the Fmr1
      knockout mouse model for fragile X.
AB  - Fragile X, an inheritable form of mental retardation, is caused by the
      inactivation of a gene on the X chromosome, FMR1 which codes for an RNA binding
      protein, fragile X mental retardation protein. Loss of this protein is associated
      with reduced complexities of neuronal dendrites and alterations in spine
      morphology in a number of cortical brain regions, and these deficits may underlie
      the cognitive impairment observed in fragile X patients. Among the many symptoms
      of fragile X are altered motor functions, although the neuronal basis for these
      remains unclear. In this study we investigated whether knockout of Fmr1 in the
      mouse model of fragile X altered dendrite morphology in developing spinal cord
      motor neurons. We find that Fmr1 knockout leads to modest alterations in the
      distribution of dendritic arbor across the span of the motor neuron dendritic
      tree in 2- and 4-week-old mice, compared to wild-type controls, consistent with
      slower rates of extension and abnormal pruning of intermediate dendritic
      segments. These studies suggest that some motor deficits in fragile X patients
      may be due to abnormal maturation of dendritic patterning within spinal motor
      neurons, and suggest that strategies aimed at preventing motor impairment in
      fragile X patients may be targeted at motor functions during early development.

PMID- 18638540
TI  - Electrophysiological characterization of BmK I, an alpha-like scorpion toxin, on
      rNav1.5 expressed in HEK293t cells.
AB  - A recent study described the pharmacological properties of BmK I, an alpha-like
      toxin from the Chinese scorpion Buthus martensi Karsch, on the cardiac sodium
      channel (hH1) expressed in Xenopus oocytes. Considering that alpha-like toxins
      are unique in their inability to bind to rat synaptosomes despite a high toxicity
      by intravenous injection, the present study investigated the pharmacological
      properties of BmK I on rNav1.5 expressed in a mammalian HEK293t cell line. The
      results include: (1) BmK I slowed and partially inhibited the inactivation of
      rNav1.5, produced a substantial persistent current and increased peak current
      (the EC(50) for increasing peak current by BmK I was 99.4+/-20.1 nM); (2) BmK I
      delayed the recovery of the sodium channel from inactivation; (3) after exposure
      to 300nM BmK I, the steady-state activation curve of rNav1.5 was negatively
      shifted by about 19 mV; and (4) the association of BmK I and rNav1.5 was faster
      than their dissociation. The results show that BmK I displayed the
      pharmacological characteristics of an alpha-like toxin on rNav1.5 channels
      expressed in HEK293t cells, and suggested that the host expression system should
      be taken into consideration when characterizing the pharmacological properties of
      toxins.

PMID- 18638542
TI  - Impact of acute bisphenol-A exposure upon intrauterine implantation of fertilized
      ova and urinary levels of progesterone and 17beta-estradiol.
AB  - Bisphenol-A (BPA), a monomer used in production of polycarbonate plastics and
      epoxy resins, has established estrogenic properties. We assessed the impact of
      acute and repeated subcutaneous BPA administration upon intrauterine implantation
      of fertilized ova and urinary levels of 17beta-estradiol and progesterone in
      inseminated female mice. In Experiment 1, females received varied doses of BPA on
      days 1-4 of gestation. Daily doses of 6.75 and 10.125mg/animal significantly
      reduced the number of implantation sites. Urinary progesterone was significantly
      reduced by the higher dose, but no other dose had an effect on progesterone
      levels and no dose altered estradiol levels. In Experiment 2, inseminated females
      received a single dose of BPA on days 0, 1, or 2 of gestation. A single dose of
      10.125mg reduced the number of implantation sites when given on day 0 or day 1,
      and 6.75mg on day 1 also produced fewer implantation sites, but there was no such
      effect of any dose when administered on day 2. These data show a lower threshold
      for BPA-induced pregnancy disruption than previously reported, also indicating
      effects of just one exposure. They confirm that this disruption is due to the
      actions of BPA upon implantation sites, and show that higher doses can influence
      systemic progesterone levels.

PMID- 18638541
TI  - Neuroendocrine modulation of cancer progression.
AB  - Clinical and animal studies now support the notion that psychological factors
      such as stress, chronic depression, and lack of social support might promote
      tumor growth and progression. Recently, cellular and molecular studies have
      started to identify biological processes that could mediate such effects. This
      review provides a mechanistic understanding of the relationship between
      biological and behavioral influences in cancer and points to more comprehensive
      behavioral and pharmacological approaches for better patient outcomes.

PMID- 18638543
TI  - Kinetics of gold nanoparticles in the human placenta.
AB  - We studied the transfer of PEGylated gold nanoparticles through perfused human
      placenta. In 'once-through' perfusions using 15 and 30nm nanoparticles both
      maternal and fetal outflows were collected. Recirculating perfusions using 10 or
      15nm nanoparticles lasted 6h. The gold concentration in samples was analysed on
      ICP-MS. The reference compound antipyrine crossed the placenta rapidly, as
      expected. In open perfusions nanoparticles were detected in maternal but not in
      fetal outflow, suggesting the lack of placental transfer. During 6h re
      circulating perfusions, no particles were detected in fetal circulation. Using
      transmission electron microscopy (TEM) and silver enhancement, nanoparticles
      could be visualized in the placental tissue mainly in the trophoblastic cell
      layer. In in vitro experiments, nanoparticles were taken up by BeWo
      choriocarcinoma cells and retained inside the cells for an extended period of
      48h. In conclusion, PEGylated gold nanoparticles of the size 10-30nm did not
      cross the perfused human placenta in detectable amounts into the fetal
      circulation within 6h. Whether PEGylated gold nanoparticles eventually are able
      to cross placenta and whether nanoparticles affect placental functions needs to
      be further studied.

PMID- 18638544
TI  - Hypoxia activates NADPH oxidase to increase [ROS]i and [Ca2+]i through the
      mitochondrial ROS-PKCepsilon signaling axis in pulmonary artery smooth muscle
      cells.
AB  - The importance of NADPH oxidase (Nox) in hypoxic responses in hypoxia-sensing
      cells, including pulmonary artery smooth muscle cells (PASMCs), remains
      uncertain. In this study, using Western blot analysis we found that the major Nox
      subunits Nox1, Nox4, p22(phox), p47(phox), and p67(phox) were equivalently
      expressed in mouse pulmonary and systemic (mesenteric) arteries. However, acute
      hypoxia significantly increased Nox activity and translocation of p47(phox)
      protein to the plasma membrane in pulmonary, but not mesenteric, arteries. The
      Nox inhibitor apocynin and p47(phox) gene deletion attenuated the hypoxic
      increase in intracellular concentrations of reactive oxygen species and Ca(2+)
      ([ROS](i) and [Ca(2+)](i)), as well as contractions in mouse PASMCs, and
      abolished the hypoxic activation of Nox in pulmonary arteries. The
      conventional/novel protein kinase C (PKC) inhibitor chelerythrine, specific
      PKCepsilon translocation peptide inhibitor, and PKCepsilon gene deletion, but not
      the conventional PKC inhibitor GO6976, prevented the hypoxic increase in Nox
      activity in pulmonary arteries and [ROS](i) in PASMCs. The PKC activator phorbol
      12-myristate 13-acetate could increase Nox activity in pulmonary and mesenteric
      arteries. Inhibition of mitochondrial ROS generation with rotenone or myxothiazol
      prevented hypoxic activation of Nox. Glutathione peroxidase-1 (Gpx1) gene
      overexpression to enhance H(2)O(2) removal significantly inhibited the hypoxic
      activation of Nox, whereas Gpx1 gene deletion had the opposite effect. Exogenous
      H(2)O(2) increased Nox activity in pulmonary and mesenteric arteries. These
      findings suggest that acute hypoxia may distinctively activate Nox to increase
      [ROS](i) through the mitochondrial ROS-PKCepsilon signaling axis, providing a
      positive feedback mechanism to contribute to the hypoxic increase in [ROS](i) and
      [Ca(2+)](i) as well as contraction in PASMCs.

PMID- 18638545
TI  - Curcumin protects cardiac cells against ischemia-reperfusion injury: effects on
      oxidative stress, NF-kappaB, and JNK pathways.
AB  - In this study we explored the effects of curcumin in cardiac cells subjected to a
      protocol simulating ischemia-reperfusion (IR). Curcumin (10 microM) was
      administered before ischemia (pretreatment) or at the moment of reperfusion
      (posttreatment) and its effects were compared to those produced by a reference
      antioxidant (Trolox) with an equal antioxidant capacity. IR cardiac cells showed
      clear signs of oxidative stress, impaired mitochondrial activity, and a marked
      development of both necrotic and apoptotic processes; at the same time, increases
      in NF-kappaB nuclear translocation and JNK phosphorylation were observed.
      Curcumin pretreatment was revealed to be the most effective in attenuating all
      these modifications and, in particular, in reducing the death of IR cells. This
      confirms that the protective effect of curcumin is not related simply to its
      antioxidant properties but involves other mechanisms, notably interactions in the
      NF-kappaB and JNK pathways. These findings suggest that curcumin administration,
      in particular before the hypoxic challenge, represents a promising approach to
      protecting cardiac cells against IR injury. In this scenario our results point
      out the importance of the chronology for the outcome of the treatment and provide
      a differential valuation of the degree of protection that curcumin can exert by
      its antioxidant activity or by other mechanisms.

PMID- 18638546
TI  - Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide
      glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac
      dysfunction.
AB  - Ischemia/reperfusion (I/R) injury elicits damage to mitochondria. Antioxidants
      provide protection from I/R-induced mitochondrial damage. The goal of this study
      was to determine the impact of mitochondria-specific overexpression of GPx4
      (PHGPx) on cardiac function following I/R. Transgenic mice were created in which
      PHGPx was overexpressed solely in the mitochondrion (mPHGPx). MPHGPx and
      littermate control hearts were subjected to global no-flow ischemia (20 min)
      followed by reflow reperfusion (30, 60, and 90 min). Following I/R, mPHGPx hearts
      possessed significantly better rates of contraction, developed pressures, and
      peak-systolic pressures as compared to controls (P<0.05). No differences were
      observed in rates of relaxation or end-diastolic pressures. Lipid peroxidation
      was significantly lower in mitochondria from mPHGPx hearts as compared to
      controls, following I/R (P<0.05). Electron transport chain (ETC) complex I, III,
      and IV activities were significantly higher in mPHGPx hearts as compared to
      controls, following I/R (P<0.05). MPHGPx overexpression enhanced ETC complex I,
      III, and IV activities in subsarcolemmal mitochondria (SSM; P<0.05), and ETC
      complex I and III activities in interfibrillar mitochondria (IFM; P<0.05)
      following I/R. These results indicate that mitochondria-specific GPx4
      overexpression protects cardiac contractile function and preserves ETC complex
      activities following I/R. These results provide further rationale for the use of
      mPHGPx as a therapeutic protectant.

PMID- 18638547
TI  - Inhibition of the thioredoxin system is a basis for the antileukemic potential of
      13-hydroxy-15-oxo-zoapatlin.
AB  - The mammalian thioredoxin (Trx) system, composed of Trx, Trx reductase (TrxR),
      and NADPH, is the most important thiol system involved in the redox control of
      signaling and regulatory proteins in apoptosis and cell proliferation. Here we
      addressed the inhibition of the Trx system by 13-hydroxy-15-oxo-zoapatlin (OZ), a
      nor-kaurane diterpene previously shown to possess proapoptotic potential and to
      cause cell cycle arrest in leukemia cells. OZ was found, by both biochemical and
      mass spectrometry-based approaches, to target Trx1 and TrxR in a cell-free
      system. In particular, the formation of reversible OZ adducts to Trx1 Cys35,
      Cys62, and Cys73 was demonstrated. We next showed that OZ efficiently inhibited
      Trx and TrxR catalytic activity in Molt4 cells. The occurrence of oxidative
      modifications of Trx molecules was assessed by "redox Western blot" analyses. OZ
      mediated Trx oxidation resulted in apoptosis signaling kinase-1 release and
      activation of downstream JNK and p38 pathways. By means of specific inhibitors of
      these two stress-activated protein kinases, we demonstrated that the JNK pathway
      plays a major role in determining the apoptotic fate of OZ-exposed cells, whereas
      p38 activation seems to be involved mainly in OZ-induced G2/M block.

PMID- 18638548
TI  - Construction of an improved RP4 (RK2)-based conjugative system.
AB  - In many bacteria, gene replacement can only be achieved using RP4-based
      conjugative systems where exogenous DNA is delivered to the recipient on
      conditionally replicating plasmids carrying an oriT(RP4). In the commonly used
      strains SM10 and S17-1 conjugative functions are provided by an RP4 plasmid
      inserted in the chromosome. Those strains, besides mobilizing oriT(RP4)-carrying
      plasmids, also transfer their own chromosomal genes, which can be inconvenient
      for several reasons. We describe here a new version of an RP4-based conjugative
      system that allows for efficient transfer of mobilizable plasmids without the
      transfer of chromosomal genes, providing fully controlled and efficient
      exogeneous DNA delivery to non-transformable bacteria.

PMID- 18638549
TI  - Activating transcription factor-2 affects skeletal growth by modulating pRb gene
      expression.
AB  - Endochondral ossification is the process of skeletal bone growth via the
      formation of a cartilage template that subsequently undergoes mineralization to
      form trabecular bone. Genetic mutations affecting the proliferation or
      differentiation of chondrocytes result in skeletal abnormalities. Activating
      transcription factor-2 (ATF-2) modulates expression of cell cycle regulatory
      genes in chondrocytes, and mutation of ATF-2 results in a dwarfed phenotype. Here
      we investigate the regulatory role that ATF-2 plays in expression of the pocket
      proteins, cell cycle regulators important in cellular proliferation and
      differentiation. The spatial and temporal pattern of pocket protein expression
      was identified in wild type and mutant growth plates. Expression of
      retinoblastoma (pRb) mRNA and protein were decreased in ATF-2 mutant primary
      chondrocytes. pRb mRNA expression was coordinated with chondrogenic
      differentiation and cell cycle exit in ATDC5 cells. Type X collagen
      immunohistochemistry was performed to visualize a delay in differentiation in
      response to loss of ATF-2 signaling. Chondrocyte proliferation was also affected
      by loss of ATF-2. These studies suggest pRb plays a role in chondrocyte
      proliferation, differentiation and growth plate development by modulating cell
      cycle progression. ATF-2 regulates expression of pRb within the developing growth
      plate, contributing to the skeletal phenotype of ATF-2 mutant mice through the
      regulation of chondrocyte proliferation and differentiation.

PMID- 18638550
TI  - alphavbeta3 integrin and angiogenesis: a moody integrin in a changing
      environment.
AB  - In the adult, angiogenesis, the formation of new blood vessels from pre-existing
      vasculature contributes to the pathogenesis of many disorders including cancer.
      The role of adhesion molecules, especially integrins, in pathological
      angiogenesis has long been the subject of investigation, mostly because of their
      potential as anti-angiogenic targets. Recent studies have highlighted the
      complexities connected with understanding the roles of one particular integrin,
      alphavbeta3, in neovascularization. This integrin is notoriously promiscuous and
      its precise functions in angiogenesis are unclear. Here, I have firstly
      summarized some of the salient features of the roles played by alphavbeta3 during
      angiogenesis; secondly attempted to address the apparently conflicting issues
      surrounding this topic; and finally raised some questions that appear to be
      unanswered.

PMID- 18638551
TI  - Ion fluxes and neurotransmitters signaling in neural development.
AB  - The brain develops and functions in a complex ionic milieu, which is a
      prerequisite for neurotransmitter function and neuronal signaling.
      Neurotransmitters and ion fluxes are, however, important not only in neuronal
      signaling, but also in the control of neural differentiation, and in this review,
      we highlight the recent advances in our understanding of how the gamma-amino
      butyric acid (GABA) neurotransmitter and ion fluxes are relevant for cell cycle
      control and neural differentiation. Conversely, proteins previously associated
      with ion transport across membranes have been endowed with novel ion-independent
      functions, and we discuss this in the context of gap junctions in cell adhesion
      and of the neuron-specific K(+)-Cl(-) cotransporter KCC2 in dendritic spine
      development. Collectively, these findings provide a richer and more complex
      picture of when ion fluxes are needed in neural development and when they are
      not.

PMID- 18638552
TI  - Understanding mechanisms governing protein-protein interactions from synthetic
      binding interfaces.
AB  - Recent advances in methodologies and design of combinatorial library selection
      have enabled comprehensive characterization of sequence space for protein-protein
      interaction interfaces and generation of fully synthetic binding interfaces. By
      exhaustively introducing and quantitatively analyzing mutations in natural
      interfaces, new insights into their molecular architecture and plasticity have
      emerged. Minimalist combinatorial libraries based on a restricted amino acid code
      have produced synthetic interfaces that rival natural ones using a different set
      of rules. A two amino acid code composed of just tyrosine and serine in the
      context of antibody CDR loops is sufficient to produce high affinity and specific
      interactions with different classes of protein targets. Structural analyses
      highlight the dominant role of Tyr in forming productive interactions and
      demonstrate the dominance of conformational diversity over chemical diversity in
      producing naive binding interfaces. Synthetic binding proteins are beginning to
      be used as a powerful crystallization tool to attack important structural biology
      problems that are recalcitrant to crystallization using traditional methods.

PMID- 18638553
TI  - Effect of chronic stress or nicotine on hypothyroidism-induced enhancement of
      LTD: electrophysiological and molecular studies.
AB  - We have shown recently that either hypothyroidism or chronic psychosocial stress
      enhances the expression of LTD, which is reversed by chronic nicotine treatment.
      In this study, we investigated the effect of combining chronic psychosocial
      stress with hypothyroidism on LTD. We have also investigated the levels of
      signaling molecules important for LTD in hypothyroid, stressed-hypothyroid and
      nicotine-treated hypothyroid rats. Following paired pulse stimulation, LTD was
      evoked in the CA1 region of anesthetized rats. Combining chronic psychosocial
      stress with hypothyroidism does not further enhance LTD magnitude compared to
      either alone. Western blot analysis conducted 1 h after induction of LTD, showed
      that the levels of calcineurin and P-CaMKII were increased in hypothyroid and
      stressed-hypothyroid groups compared to that of the control group. However, the
      levels of calcineurin and P-CaMKII after paired pulsed stimulation were not
      further increased in stressed-hypothyroid group compared to the hypothyroid only
      group. In addition, these levels were normalized by chronic nicotine treatment.
      No change was detected in any of the groups in the levels of calmodulin,
      PKCgamma, and BDNF after paired pulse stimulation. Our results indicate that
      changes in the levels of calcineurin and P-CaMKII during expression of LTD in the
      CA1 region may explain the enhanced magnitude of LTD in hypothyroid rats, and its
      reversal by chronic nicotine treatment.

PMID- 18638554
TI  - Decorin promotes robust axon growth on inhibitory CSPGs and myelin via a direct
      effect on neurons.
AB  - Inhibitory chondroitin sulfate proteoglycans (CSPGs) and myelin-associated
      molecules are major impediments to axon regeneration within the adult central
      nervous system (CNS). Decorin infusion can however suppress the levels of
      multiple inhibitory CSPGs and promote axon growth across spinal cord injuries
      [Davies, J.E., Tang, X., Denning, J.W., Archibald, S.J., and Davies, S.J., 2004.
      Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes
      axon growth across adult rat spinal cord injuries. Eur. J. Neurosci. 19, 1226
      1242]. A question remained as to whether decorin can also increase axon growth on
      inhibitory CSPGs and myelin via a direct effect on neurons. We have therefore
      conducted an in vitro analysis of neurite extension by decorin-treated adult
      dorsal root ganglion (DRG) neurons cultured on substrates of inhibitory CSPGs or
      myelin membranes mixed with laminin. Decorin treatment promoted 14.5 and 5-fold
      increases in average neurite length/neuron over untreated controls on CSPGs or
      myelin membranes respectively. In addition to suppressing inhibitory scar
      formation, our present data shows that decorin can directly boost the ability of
      neurons to extend axons within CSPG or myelin rich environments.

PMID- 18638555
TI  - The role of the inherited genetic background on the consequences of lithium
      pilocarpine status epilepticus: study in Genetic Absence Epilepsy Rats from
      Strasbourg and Wistar audiogenic rats.
AB  - The susceptibility of rats with genetically inherited epilepsy to the genesis and
      consequences of secondary temporal lobe epilepsy is unknown. Here, we induced
      lithium-pilocarpine status epilepticus (SE) in Genetic Absence Epilepsy Rats from
      Strasbourg (GAERS) or in Wistar audiogenic sensitive (AS) rats. Wistar AS needed
      less pilocarpine than GAERS and Non-Epileptic Rats (NERs) to develop SE. Sixty
      six, 40 and 5% of Wistar AS, GAERS and NERs, respectively, died within 24 h after
      SE. In GAERS, SE prevented the occurrence of absence seizures for 5 days.
      Thereafter a limited number of absence seizures with low amplitude and short
      duration were recorded. Wistar AS developed limbic epilepsy within 9 days after
      SE while GAERS and NERs needed 36-39 days to develop spontaneous motor seizures.
      Neuronal loss consecutive to SE was similar in the three strains and particularly
      marked in limbic forebrain and parahippocampal cortices. In conclusion, the
      development of focal limbic epilepsy in GAERS largely impairs the expression of
      absence seizures. The genetic background underlying the expression of audiogenic
      seizures sensitizes strongly the rats to a further insult and compromises their
      survival.

PMID- 18638556
TI  - Rodent genetic models of Huntington disease.
AB  - Huntington disease (HD) is a dominantly inherited human neurodegenerative
      disorder characterized by motor deficits, cognitive impairment, and psychiatric
      symptoms leading to inexorable decline and death. Since the identification of the
      huntingtin gene and the characteristic expanded CAG repeat/polyglutamine
      mutation, multiple murine genetic models and one rat genetic model have been
      generated. These models fall into two general categories: transgenic models with
      ectopic expression of the characteristic expanded CAG codon mutation, and knock
      in models with expression of mutant huntingtin under control of endogenous
      regulatory elements. Rodent genetic models are valuable tools for studying
      mechanisms of pathogenesis in HD and for preclinical evaluation of possible
      therapies. In this mini-review, we provide a concise comparative summary of
      rodent genetic models of HD.

PMID- 18638557
TI  - Hippocampal bursts caused by changes in NMDA receptor-dependent excitation in a
      mouse model of variant CJD.
AB  - Prion diseases are heterogeneous in clinical presentation, suggesting that
      different prion diseases have distinct pathophysiological changes. To understand
      the pathophysiology specific to variant Creutzfeldt-Jakob Disease (vCJD), in
      vitro electrophysiological studies were performed in a mouse model in which human
      derived vCJD prions were transmitted to transgenic mice expressing human instead
      of murine prion protein. Paired-pulse stimulation of the Schaffer collaterals
      evoked hypersynchronous bursting in the hippocampus of vCJD-inoculated mice;
      comparable bursts were never observed in control or Prnp knockout mice, or in
      mice inoculated with a strain of prion associated with classical CJD.
      Furthermore, NMDA receptor-mediated excitation was increased in vCJD-inoculated
      mice. Using pharmacological experiments and computer simulations, we demonstrate
      that the increase in NMDA receptor-mediated excitation is necessary and
      sufficient to explain the distinctive bursting pattern in vCJD. These
      pathophysiological changes appear to result from a prion strain-specific gain-of
      function and may explain some of the distinguishing clinical features of vCJD.

PMID- 18638558
TI  - Nr4a2 is essential for the differentiation of dopaminergic neurons during
      zebrafish embryogenesis.
AB  - Nr4a2 is a member of the orphan nuclear receptor gene superfamily, which has been
      found to be critical for the development and maintenance of mesencephalic
      dopaminergic (DA) neurons. To uncover the molecular mechanisms by which Nr4a2
      contributes to the development of DA neurons, we have applied zebrafish to study
      the topographic distribution of nr4a2b transcripts, as well as its correlation
      with neuronal progenitor marker (neurogenin 1) and DA neuron markers (tyrosine
      hydroxylase, TH and DA transporter, DAT) during neurogenesis. Our studies showed
      that although nr4a2b transcripts did not co-localize with TH and DAT transcripts
      in the posterior tuberculum (PT area), knockdown of Nr4a2 resulted in a
      significant decrease of TH(+) and DAT(+) DA neurons in the PT area, accompanied
      by a reduction of DA transmitter, which were partially rescued by the injection
      of mouse Nr4a2 mRNA. Surprisingly, the number of nr4a2b(+) cells in Nr4a2
      deficient embryos was increased by 1.6 fold. These results suggest that Nr4a2 may
      play an important role in the differentiation and maturation rather than the
      survival of DA progenitors in the PT area during zebrafish early embryogenesis.

PMID- 18638559
TI  - Dopamine transporter endocytic determinants: carboxy terminal residues critical
      for basal and PKC-stimulated internalization.
AB  - Dopamine (DA) reuptake terminates dopaminergic neurotransmission and is mediated
      by DA transporters (DATs). Acute protein kinase C (PKC) activation accelerates
      DAT internalization rates, thereby reducing DAT surface expression. Basal DAT
      endocytosis and PKC-stimulated DAT functional downregulation rely on residues
      within the 587-596 region, although whether PKC-induced DAT downregulation
      reflects transporter endocytosis mechanisms linked to those controlling basal
      endocytosis rates is unknown. Here, we define residues governing basal and PKC
      stimulated DAT endocytosis. Alanine substituting DAT residues 587-590 1)
      abolished PKC stimulation of DAT endocytosis, and 2) markedly accelerated basal
      DAT internalization, comparable to that of wildtype DAT during PKC activation.
      Accelerated basal DAT internalization relied specifically on residues 588-590,
      which are highly conserved among SLC6 neurotransmitter transporters. Our results
      support a model whereby residues within the 587-590 stretch may serve as a locus
      for a PKC-sensitive braking mechanism that tempers basal DAT internalization
      rates.

PMID- 18638560
TI  - Histone deacetylase inhibitors improve learning consolidation in young and in KA
      induced-neurodegeneration and SAMP-8-mutant mice.
AB  - Histone deacetylases (HDAC) are enzymes that maintain chromatin in a condensate
      state, related with absence of transcription. We have studied the role of HDAC on
      learning and memory processes. Both eyeblink classical conditioning (EBCC) and
      object recognition memory (ORM) induced an increase in histone H3 acetylation (Ac
      H3). Systemic treatment with HDAC inhibitors improved cognitive processes in EBCC
      and in ORM tests. Immunohistochemistry and gene expression analyses indicated
      that administration of HDAC inhibitors decreased the stimulation threshold for Ac
      H3, and gene expression to reach the levels required for learning and memory.
      Finally, we evaluated the effect of systemic administration of HDAC inhibitors to
      mice models of neurodegeneration and aging. HDAC inhibitors reversed learning and
      consolidation deficits in ORM in these models. These results point out HDAC
      inhibitors as candidate agents for the palliative treatment of learning and
      memory impairments in aging and in neurodegenerative disorders.

PMID- 18638561
TI  - Complete plastid genome sequence of the chickpea (Cicer arietinum) and the
      phylogenetic distribution of rps12 and clpP intron losses among legumes
      (Leguminosae).
AB  - Chickpea (Cicerarietinum, Leguminosae), an important grain legume, is widely used
      for food and fodder throughout the world. We sequenced the complete plastid
      genome of chickpea, which is 125,319bp in size, and contains only one copy of the
      inverted repeat (IR). The genome encodes 108 genes, including 4 rRNAs, 29 tRNAs,
      and 75 proteins. The genes rps16, infA, and ycf4 are absent in the chickpea
      plastid genome, and ndhB has an internal stop codon in the 5'exon, similar to
      other legumes. Two genes have lost their introns, one in the 3'exon of the
      transpliced gene rps12, and the one between exons 1 and 2 of clpP; this
      represents the first documented case of the loss of introns from both of these
      genes in the same plastid genome. An extensive phylogenetic survey of these
      intron losses was performed on 302 taxa across legumes and the related family
      Polygalaceae. The clpP intron has been lost exclusively in taxa from the
      temperate "IR-lacking clade" (IRLC), whereas the rps12 intron has been lost in
      most members of the IRLC (with the exception of Wisteria, Callerya, Afgekia, and
      certain species of Millettia, which represent the earliest diverging lineages of
      this clade), and in the tribe Desmodieae, which is closely related to the tribes
      Phaseoleae and Psoraleeae. Data provided here suggest that the loss of the rps12
      intron occurred after the loss of the IR. The two new genomic changes identified
      in the present study provide additional support of the monophyly of the IR-loss
      clade, and resolution of the pattern of the earliest-branching lineages in this
      clade. The availability of the complete chickpea plastid genome sequence also
      provides valuable information on intergenic spacer regions among legumes and
      endogenous regulatory sequences for plastid genetic engineering.

PMID- 18638562
TI  - Combination of bone tissue engineering and BMP-2 gene transfection promotes bone
      healing in osteoporotic rats.
AB  - OBJECTIVE: The aim of this study was to develop a feasible approach to promote
      bone healing in osteoporotic rats using autogenous bone tissue-engineering and
      gene transfection of human bone morphogenetic protein 2 (hBMP-2). METHODS: Bone
      marrow stromal cells (BMSCs) from the left tibia of osteoporotic rats were
      transfected with the hBMP-2 gene in vitro which was confirmed by
      immunohistochemistry, in situ hybridization and Western blotting. Autogenous
      transfected or untransfected BMSCs were seeded on macroporous coral
      hydroxyapatite (CHA) scaffolds. Each cell-scaffold construct was implanted into a
      defect site which was created in the ramus of the mandible of osteoporotic rats.
      Four or eight weeks after implantation in situ hybridization was performed in
      BMSCs transfected with hBMP-2, X-ray examinations, histological and
      histomorphological analyses were used to evaluate the effect of tissue-engineered
      bone on osseous defect repair. RESULTS: Newly formed bone was observed at the
      margin of the defect 4 weeks after implantation with BMSCs transfected with BMP
      2. Mature bone was observed 8 weeks after treatment. In the control group there
      was considerably less new bone and some adipose tissue was observed at the defect
      margins 8 weeks after implantation. CONCLUSIONS: Autogenous cells transfected
      with hBMP-2 promote bone formation in osteoporotic rats. BMSC-mediated BMP-2 gene
      therapy used in conjunction with bone tissue engineering may be used to
      successfully treat bone defects in osteoporotic rats. This method provides a
      powerful tool for bone regeneration and other tissue engineering.

PMID- 18638563
TI  - Molecular characterization and expression patterns of AMP deaminase1 (AMPD1) in
      porcine skeletal muscle.
AB  - AMPD1 is the muscle-specific form of the AMPD multigene families in mammals and
      plays an important role in the purine nucleotide cycle and energy metabolism in
      skeletal muscle. In this study, we cloned and characterized AMPD1 from Sus scrofa
      muscle. The promoter of porcine AMPD1 contained several putative muscle-specific
      transcription factor binding sites (E box, myogenin, MEF2, Spl-CTF/NF-l), one
      RORalpha2 binding motif and NF-kappaB site. The deduced amino acid sequence of
      porcine AMPD1 contains an AMP deaminase signature sequence (SLSTDDP). RT-PCR
      analyses showed that AMPD1 was expressed specifically in skeletal muscle.
      Expression of AMPD1 was up-regulated during the muscle development and was higher
      in Yorkshire than in Meishan pigs. AMPD1 gene was expressed at higher levels in
      longissimus dorsi and bicepsfemoris muscles compared with soleus and masseter
      muscles in both Yorkshire and Meishan pigs. Moreover, we found that a single
      nucleotide polymorphism (SNP, T/C(426)) in exon12 of the AMPD1 gene was
      significantly associated with loin muscle area trait (p<0.01), loin muscle height
      (p<0.01) and average backfat thickness (p<0.05). This result suggests that the
      AMPD1 gene might be a candidate gene of meat production trait and provides useful
      information for further studies on its roles in porcine skeletal muscle.

PMID- 18638564
TI  - Prostaglandin F(2alpha) negatively regulates bone resorption in murine osteoclast
      development.
AB  - Prostaglandin (PG) E(2) promotes osteoclastic cell differentiation, but the
      physiological function of PGF(2alpha) remains unclear. We examined the
      physiological effects of PGF(2alpha) on osteoclast differentiation using a murine
      cell line, RAW264, and the column-purified murine bone marrow cells, both of
      which are differentiable into osteoclast-like multi-nuclear cells. Although
      PGF(2alpha) did not affect the number of differentiated osteoclasts, PGF(2alpha)
      reduced the bone resorption activity of osteoclasts developed from both cell
      types in a pit formation assay. Thus, PGF(2alpha) inhibits bone resorption
      without affecting the number of osteoclasts, providing a novel molecular
      mechanism underlying bone metabolism.

PMID- 18638565
TI  - Assessment of biomarkers in asbestos-exposed workers as indicators of cancer
      risk.
AB  - Epidemiological studies have shown that mortality from malignant mesothelioma
      (MM) and lung cancer have increased with increasing cumulative exposure to
      asbestos. To investigate whether tumour-related biomarkers can contribute towards
      the evaluation of the carcinogenic risk in populations exposed to asbestos, the
      DNA adduct 8-hydroxy-2'-deoxyguanosine (80HdG), interleukine-6 (IL-6), platelet
      derived growth factor (PDGF-BB), hepatocyte growth factor (HGF), basic fibroblast
      growth factor (bFGF), vascular endothelial growth factor (VEGFbeta) and soluble
      mesothelin-related peptides (SMRPs) were analysed in a cohort of workers
      differently exposed to asbestos fibres at the workplace. To document biomarker
      levels in an unexposed population, 54 age-matched subjects were enrolled. A total
      of 119 subjects with a history of occupational exposure to asbestos underwent
      clinical examination and were interviewed by trained personnel, responding to a
      detailed questionnaire related to duration of asbestos exposure, smoking, and
      occupational task. According to the occupational tasks, asbestos-exposed subjects
      were analysed for their asbestos cumulative dose and the association with the
      biomarkers was evaluated. Among the occupational groups, maintenance workers,
      pipe fitters and electricians were exposed to a higher cumulative dose of
      asbestos fibres. Exposure to asbestos significantly increased the steady-state
      content of 80HdG in DNA. Elevated levels of 80HdG and IL-6 best reflected a high
      level of SMRPs, which is related to cell transformation. Subjects heavily exposed
      to asbestos [> 60(ff/cm3) x years] showed also a higher level of angiogenic
      factors. A combination of angiogenic biomarkers with a specific mesothelioma
      biomarker such as SMRPs could be used for close surveillance of workers with a
      history of asbestos exposure.

PMID- 18638566
TI  - Genotoxic effects of Roundup on the fish Prochilodus lineatus.
AB  - Glyphosate-based herbicides, such as Roundup, represent the most extensively used
      herbicides worldwide, including Brazil. Despite its extensive use, the genotoxic
      effects of this herbicide are not completely understood and studies with Roundup
      show conflicting results with regard to the effects of this product on the
      genetic material. Thus, the aim of this study was to evaluate the genotoxic
      effects of acute exposures (6, 24 and 96 h) to 10 mg L(-1) of Roundup on the
      neotropical fish Prochilodus lineatus. Accordingly, fish erythrocytes were used
      in the comet assay, micronucleus test and for the analysis of the occurrence of
      nuclear abnormalities and the comet assay was adjusted for branchial cells. The
      results showed that Roundup produces genotoxic damage in erythrocytes and gill
      cells of P. lineatus. The comet scores obtained for P. lineatus erythrocytes
      after 6 and 96 h of exposure to Roundup were significantly higher than respective
      negative controls. For branchial cells comet scores were significantly higher
      than negative controls after 6 and 24 h exposures. The frequencies of
      micronucleus and other erythrocyte nuclear abnormalities (ENAs) were not
      significantly different between Roundup exposed fish and their respective
      negative controls, for all exposure periods. In conclusion, the results of this
      work showed that Roundup produced genotoxic effects on the fish species P.
      lineatus. The comet assay with gill cells showed to be an important complementary
      tool for detecting genotoxicity, given that it revealed DNA damage in periods of
      exposure that erythrocytes did not. ENAs frequency was not a good indicator of
      genotoxicity, but further studies are needed to better understand the origin of
      these abnormalities.

PMID- 18638567
TI  - Toxicogenomics of arsenic: classical ideas and recent advances.
AB  - Exposure to arsenic, a toxic metalloid distributed widely in nature, has been
      known to result in hazardous health outcomes including cancer. Incidence of
      arsenic toxicity, mostly from usage of underground water, has been reported from
      different corners of the world spanning more than 21 countries. Recent studies
      have radically influenced our knowledge on the level of toxicity imparted by
      different chemical forms of the metalloid. To understand the basic biology for
      arsenic metabolism different species have been studied at the molecular level,
      which has unraveled a wealth of information. However, there is no ideal animal
      model that can be used to understand arsenic toxicity in humans prompting the
      investigators to undertake the study directly in human cell lines and on affected
      individuals in areas of exposure. It is interesting to note that only a subset of
      exposed individuals demonstrate pathological features, i.e. skin lesions
      sometimes followed by cancer. Also, the extent of affectedness varies remarkably
      between individuals exposed to similar levels of arsenic. These observations led
      to investigation of genomic variation in exposed individuals as a potential
      contributing factor for differential susceptibility. An impressive number of
      studies have been published on variation in global gene expression and the
      potential association of candidate genes with arsenic-induced pathology. While
      there are excellent reviews relating to arsenic metabolism in general, there is
      no comprehensive review presenting the studies described in humans related to the
      metalloid toxicity. Our goal in this article has been to present the current
      state of research on this area to help formulate strategies for future studies.

PMID- 18638568
TI  - Sphingosine 1-phosphate chemical biology.
AB  - A dozen years ago, the term 'S1P' (sphingosine 1-phosphate) was not in the
      lexicons of scientific literature databases. By early 2008, this query term
      retrieved well over 1000 citations from PubMed - about 225 of these appeared in
      2007. Indeed, S1P is arguably the most heavily studied lipid molecule at present.
      What happened to distinguish S1P among many other signaling lipids? We believe
      that the seminal event was the linking of the investigational drug, FTY720
      (fingolimod), to S1P signaling. This realization profoundly altered understanding
      of S1P biology, revealing both that S1P is prominent in lymphocyte trafficking
      and that mimicking S1P signaling with an agonist drug can modulate the immune
      system to considerable therapeutic benefit. Neither fact was known prior to
      FTY720; indeed, this molecule is testament to the power of chemical biology. In
      this communication, we attempt to summarize progress to date in S1P chemical
      biology.

PMID- 18638569
TI  - S1P and eNOS regulation.
AB  - In the mammalian cardiovascular system, nitric oxide (NO), a small diffusible
      gaseous signal mediator, plays pivotal roles in the maintenance of vascular
      homeostasis. The endothelial isoform of nitric oxide synthase (eNOS) is activated
      by diverse agonist-modulated cell surface receptors, and eNOS-derived NO is a key
      determinant of blood pressure, platelet activation, angiogenesis and other
      fundamental responses in the vascular wall. Sphingosine 1-phosphate (S1P) has
      recently been identified as an important activator of eNOS. This review
      summarizes the roles of sphingosine 1-phosphate and S1P receptors in eNOS
      activation, and analyzes the eNOS regulatory processes evoked by S1P. The
      implications of S1P activation of eNOS in cardiovascular (patho)physiology will
      be also discussed.

PMID- 18638570
TI  - The role of sphingosine kinase 1 in cancer: oncogene or non-oncogene addiction?
AB  - Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyses the phosphorylation
      of sphingosine to sphingosine-1-phosphate. There is strong evidence from cellular
      or animal systems that SphK1 is involved in the major mechanisms underpinning
      oncogenesis, namely, the promotion of cellular survival, proliferation and
      transformation, the prevention of apoptosis and the stimulation of angiogenesis.
      Furthermore there is also good evidence from clinical samples that SphK1 is
      overexpressed in many, if not most tumor types examined and that many inhibitors
      of SphK1 render tumors sensitive to chemotherapeutic agents. A major question
      that remains concerns the exact mechanism of action of SphK1 in cancer. The tools
      available to probe SphK1 function perturb a set of cellular functions, and it is
      possible that several of these are involved in driving its oncogenic role.
      Furthermore, the importance of SphK1 functions in normal physiology and the lack
      of mutations of SphK1 in cancer, suggest that the mechanism in cancer might be an
      over reliance on this system of cellular signaling; an example of non-oncogene
      addiction.

PMID- 18638571
TI  - Developmental patterns in the polyembryonic parasitoid wasp Copidosoma koehleri.
AB  - Polyembryony is a unique mode of development in which multiple genetically
      identical embryos develop from a single egg. In some polyembryonic species a
      proportion of the embryos develop into soldier larvae, which attack competitors
      in the host. We studied the development of the polyembryonic wasp Copidosoma
      koehleri in its host Phthorimaea opercullela. We dissected hosts parasitized by
      either virgin or mated female wasps at 2day intervals from hatching to the final
      instars. We documented host mass and head width, the number and size of
      developing wasps and the presence of a soldier larva. Additionally, we kept a
      sample of parasitized hosts until emergence of wasps and measured the head width
      of emerging adults. We characterized wasp development in relation to host
      development. One half of the broods produced by mated wasps contained one soldier
      larva throughout development. This suggests that in C. koehleri each female brood
      produces a single soldier larva, and that the soldier probably survives and grows
      gradually during host development. Additionally, we found that female broods were
      larger than male broods during development and also upon emergence. Accordingly,
      body size was larger for males during development as well as upon emergence.
      These findings may extend the existing knowledge on polyembryonic development in
      general, and serve as a baseline for further experiments.

PMID- 18638572
TI  - Functions of base flipping in E. coli nucleotide excision repair.
AB  - UvrB is the main damage recognition protein in bacterial nucleotide excision
      repair and is capable of recognizing various structurally unrelated types of
      damage. Previously we have shown that upon binding of Escherichia coli UvrB to
      damaged DNA two nucleotides become extrahelical: the nucleotide directly 3' to
      the lesion and its base-pairing partner in the non-damaged strand. Here we
      demonstrate using a novel fluorescent 2-aminopurine-menthol modification that the
      position of the damaged nucleotide itself does not change upon UvrB binding. A co
      crystal structure of B. caldotenax UvrB and DNA has revealed that one nucleotide
      is flipped out of the DNA helix into a pocket of the UvrB protein where it stacks
      on Phe249 [J.J. Truglio, E. Karakas, B. Hau, H. Wang, M.J. DellaVecchia, B. van
      Houten, C. Kisker, Structural basis for DNA recognition and processing by UvrB,
      Nat. Struct. Mol. Biol. 13 (2006) 360-364]. By mutating the equivalent of Phe249
      (Tyr249) in the E. coli UvrB protein we show that on damaged DNA neither of the
      extrahelical nucleotides is inserted into this protein pocket. The mutant UvrB
      protein, however, resulted in an increased binding and incision of undamaged DNA
      showing that insertion of a base into the nucleotide-binding pocket is important
      for dissociation of UvrB from undamaged sites. Replacing the nucleotides in the
      non-damaged strand with a C3-linker revealed that the extruded base in the non
      damaged strand is not directly involved in UvrB-binding or UvrC-mediated
      incision, but that its displacement is needed to allow access for residues of
      UvrB or UvrC to the neighboring base, which is directly opposite the DNA damage.
      This interaction is shown to be essential for optimal 3'-incision by UvrC. After
      3'-incision base flipping in the non-damaged DNA strand is lost, indicative for a
      conformational change needed to prepare the UvrB-DNA complex for 5'-incision.

PMID- 18638573
TI  - Replication fork arrest, recombination and the maintenance of ribosomal DNA
      stability.
AB  - There is increasing interest in the role of replication fork arrest and collapse
      in stimulating genomic instability. Changes in the copy number of the rDNA
      repeats mediated by homologous recombination has been linked to programmed
      replication fork barriers (RFBs) and this has been proposed to serve as a
      paradigm to help understand the links between replication and recombination. Here
      we review recent advances in our understanding of the initiation and regulation
      rDNA recombination and discuss historical observations in the context of recently
      developed models. We contrast the outcome of replication fork arrest at the rDNA
      RFB with those at an alternative RFB and suggest that, while there are potential
      similarities in response, there are also important differences which reflect the
      highly specialised nature of rDNA metabolism.

PMID- 18638575
TI  - Modeling neutrophil transport in pulmonary capillaries.
AB  - Neutrophils can be retained in the pulmonary microvasculature due to their low
      deformability, resulting in having a higher concentration there than in the
      systemic circulation, even in normal lungs. It is thought that this high
      concentration of the cells facilitates their effective recruitment to sites of
      inflammation. Thus, in order to understand their role in the immune system in the
      lungs, where blood comes in contact with outer air via thin septa of alveoli, it
      is important to clarify their flow characteristics in the pulmonary capillary
      bed. However, in contrast to erythrocytes in systemic capillaries, little
      research has been performed on the flow of neutrophils in pulmonary capillaries.
      This may be partly because no complete rheological model of the cell has been
      established yet, and partly because pulmonary capillaries are very short and
      closely interconnected, forming a complicated three-dimensional network, in
      addition to difficulty in in vivo experimental observations. Moreover, the
      neutrophils change their mechanical properties and show active motion in response
      to some chemoattractants. In this article, various proposed rheological models of
      the neutrophil, flow models of a cell through a single capillary segment, and
      alveolar capillary network models are introduced, aiming at the numerical
      simulation of neutrophil transport in the pulmonary microvasculature.

PMID- 18638574
TI  - Cell wounding and repair in ventilator injured lungs.
AB  - Acute lung injury (ALI) is a common, frequently hospital-acquired condition with
      a high morbidity and mortality. The stress associated with invasive mechanical
      ventilation represents a potentially harmful exposure, and attempts to minimize
      deforming stress through low tidal ventilation have proven efficacious. Lung
      cells are both sensors and transducers of deforming stress, and are frequently
      wounded in the setting of mechanical ventilation. Cell wounding may be one of the
      drivers of the innate immunologic and systemic inflammatory response associated
      with mechanical ventilation. These downstream effects of mechanotransduction have
      been referred to collectively as "Biotrauma". Our review will focus on cellular
      stress failure, that is cell wounding, and the mechanisms mediating subsequent
      plasma membrane repair, we hold that a better mechanistic understanding of cell
      plasticity, deformation associated remodeling and repair will reveal candidate
      approaches for lung protective interventions in mechanically ventilated patients.
      We will detail one such intervention, lung conditioning with hypertonic solutions
      as an example of ongoing research in this arena.

PMID- 18638576
TI  - Assessment of upper airway mechanics during sleep.
AB  - Obstructive sleep apnea, which is the most prevalent sleep breathing disorder, is
      characterized by recurrent episodes of upper airway collapse and reopening.
      However, the mechanical properties of the upper airway are not directly measured
      in routine polysomnography because only qualitative sensors (thermistors for flow
      and thoraco-abdominal bands for pressure) are used. This review focuses on two
      techniques that quantify upper airway obstruction during sleep. A Starling model
      of collapsible conduit allows us to interpret the mechanics of the upper airway
      by means of two parameters: the critical pressure (Pcrit) and the upstream
      resistance (Rup). A simple technique to measure Pcrit and Rup involves the
      application of different levels of continuous positive airway pressure (CPAP)
      during sleep. The forced oscillation technique is another non-invasive procedure
      for quantifying upper airway impedance during the breathing cycle in sleep
      studies. The latest developments in these two methods allow them to be easily
      applied on a routine basis in order to more fully characterize upper airway
      mechanics in patients with sleep breathing disorders.

PMID- 18638577
TI  - Proteome of Geobacter sulfurreducens grown with Fe(III) oxide or Fe(III) citrate
      as the electron acceptor.
AB  - The mechanisms for Fe(III) oxide reduction in Geobacter species are of interest
      because Fe(III) oxides are the most abundant form of Fe(III) in many soils and
      sediments and Geobacter species are prevalent Fe(III)-reducing microorganisms in
      many of these environments. Protein abundance in G. sulfurreducens grown on
      poorly crystalline Fe(III) oxide or on soluble Fe(III) citrate was compared with
      a global accurate mass and time tag proteomic approach in order to identify
      proteins that might be specifically associated with Fe(III) oxide reduction. A
      total of 2991 proteins were detected in G. sulfurreducens grown with acetate as
      the electron donor and either Fe(III) oxide or soluble Fe(III) citrate as the
      electron acceptor, resulting in 86% recovery of the genes predicted to encode
      proteins. Of the total expressed proteins 76% were less abundant in Fe(III) oxide
      cultures than in Fe(III) citrate cultures, which is consistent with the overall
      slower rate of metabolism during growth with an insoluble electron acceptor. A
      total of 269 proteins were more abundant in Fe(III) oxide-grown cells than in
      cells grown on Fe(III) citrate. Most of these proteins were in the energy
      metabolism category: primarily electron transport proteins, including 13 c-type
      cytochromes and PilA, the structural protein for electrically conductive pili.
      Several of the cytochromes that were more abundant in Fe(III) oxide-grown cells
      were previously shown with genetic approaches to be essential for optimal Fe(III)
      oxide reduction. Other proteins that were more abundant during growth on Fe(III)
      oxide included transport and binding proteins, proteins involved in regulation
      and signal transduction, cell envelope proteins, and enzymes for amino acid and
      protein biosynthesis, among others. There were also a substantial number of
      proteins of unknown function that were more abundant during growth on Fe(III)
      oxide. These results indicate that electron transport to Fe(III) oxide requires
      additional and/or different proteins than electron transfer to soluble, chelated
      Fe(III) and suggest proteins whose functions should be further investigated in
      order to better understand the mechanisms of electron transfer to Fe(III) oxide
      in G. sulfurreducens.

PMID- 18638578
TI  - Effect of surface concentration on secondary and tertiary conformational changes
      of lysozyme adsorbed on silica nanoparticles.
AB  - Kinetics of tertiary conformation of lysozyme adsorbed on 90 nm silica
      nanoparticles was inferred using tryptophan fluorescence for different surface
      concentrations (0.24 to 0.92 mg/m(2)), pH (4, 7 and 9), ionic strength (10 and
      100 mM), 2,2,2-trifluoroethanol (TFE) (5, 15 and 30%) and Dithiothreitol (DTT)
      (0.5 mg/ml) concentrations. A rapid initial unfolding, followed by a much slower
      refolding and subsequent unfolding, were observed with the extent of unfolding
      being higher at lower surface concentration, higher ionic strengths, higher TFE
      and DTT concentrations and at pH 9. The rate of unfolding was found to be higher
      at lower surface concentrations, pH 4, higher ionic strengths, higher TFE and DTT
      concentrations. In contrast, earlier results showed that beta lactoglobulin
      unfolded slower and exhibited only an initial rapid and a subsequent slow
      unfolding phase. Circular Dichroism spectra showed that alpha helix content was
      lower for adsorbed lysozyme compared to bulk with a corresponding increase in
      beta sheet and random coil. This decrease in alpha helix was found to be more
      pronounced at lower surface concentrations. DTT decreased alpha helix with a
      corresponding increase in random coil while TFE was found to have negligible
      effect on secondary structure.

PMID- 18638579
TI  - Hsp90n - An accidental product of a fortuitous chromosomal translocation rather
      than a regular Hsp90 family member of human proteome.
AB  - Human cells express two isoforms of the Hsp90 protein, called Hsp90alpha and
      Hsp90beta. Although existence of the third form called Hsp90alphaDeltaN, or
      Hsp90N was reported in 1998, our investigation, based on the sequence analysis
      and attempts to reproduce previous results, demonstrate that there is no evidence
      that Hsp90N gene is present in human genome and no homologs of such a protein are
      present in other known eukaryotic genomes. We propose that Hsp90N was created as
      an artifact of a cDNA synthesis or that it is a chimeric protein, being a result
      of the chromosomal rearrangement that occurred in a single cell line, after this
      line was established.

PMID- 18638580
TI  - Proteomic profiling of cellular targets of lipopolysaccharide-induced signalling
      in Nicotiana tabacum BY-2 cells.
AB  - Plants constantly monitor for pathogen challenge and utilize a diverse array of
      adaptive defense mechanisms, including differential protein regulation, during
      pathogen attack. A proteomic analysis of Nicotiana tabacum BY-2 cells was
      performed in order to investigate the dynamic changes following perception of
      bacterial lipopolysaccharides. A multiplexed proteome analysis, employing two
      dimensional difference-in-gel-electrophoresis with CyDye DIGE fluors, as well as
      Ruthenium II tris (bathophenanthroline disulfonate) fluorescence staining and Pro
      Q Diamond phosphoprotein-specific gel staining, monitored over 1500 proteins and
      resulted in the identification of 88 differentially regulated proteins and
      phosphoproteins responsive to LPS(B.cep.)-elicitation. Functional clustering of
      the proteins both at the level of their abundance and phosphorylation status,
      revealed 9 proteins involved in transport, ion homeostasis and signal
      transduction. A large number of responsive proteins were found to be involved in
      metabolism- and energy-related processes (36), representing various metabolic
      pathways. Another abundant category corresponded to proteins classified as
      molecular chaperones and involved in protein destination/targeting (12). Other
      categories of proteins found to be LPS(B.cep.)-responsive and differentially
      regulated include cell structure- and cytoskeletal rearrangement proteins (8) and
      proteins involved in transcription and translation as well as degradation (11).
      The results indicate that LPS(B.cep.) induces metabolic reprogramming and changes
      in cellular activities supporting protein synthesis, -folding, vesicle
      trafficking and secretion; accompanied by changes to the cytoskeleton and
      proteosome function. Many of the identified proteins are known to be
      interconnected at various levels through a complex web of
      activation/deactivation, complex formation, protein-protein interactions, and
      chaperoning reactions. The presented data offers novel insights and further
      evidence for the biochemical action of LPS(B.cep.) as a resistance elicitor, a
      pathogen-associated molecular pattern molecule and triggering agent of defense
      responses associated with innate immunity.

PMID- 18638581
TI  - Assessment of lectin and HILIC based enrichment protocols for characterization of
      serum glycoproteins by mass spectrometry.
AB  - Protein glycosylation is a common post-translational modification that is
      involved in many biological processes, including cell adhesion, protein-protein
      and receptor-ligand interactions. The glycoproteome constitutes a source for
      identification of disease biomarkers since altered protein glycosylation profiles
      are associated with certain human ailments. Glycoprotein analysis by mass
      spectrometry of biological samples, such as blood serum, is hampered by sample
      complexity and the low concentration of the potentially informative glycopeptides
      and -proteins. We assessed the utility of lectin-based and HILIC-based affinity
      enrichment techniques, alone or in combination, for preparation of glycoproteins
      and glycopeptides for subsequent analysis by MALDI and ESI mass spectrometry. The
      methods were successfully applied to human serum samples and a total of 86 N
      glycosylation sites in 45 proteins were identified using a mixture of three
      immobilized lectins for consecutive glycoprotein enrichment and glycopeptide
      enrichment. The combination of lectin affinity enrichment of glycoproteins and
      subsequent HILIC enrichment of tryptic glycopeptides identified 81 N
      glycosylation sites in 44 proteins. A total of 63 glycosylation sites in 38
      proteins were identified by both methods, demonstrating distinct differences and
      complementarity. Serial application of custom-made microcolumns of mixed,
      immobilized lectins proved efficient for recovery and analysis of glycopeptides
      from serum samples of breast cancer patients and healthy individuals to assess
      glycosylation site frequencies.

PMID- 18638582
TI  - Usefulness of changes in left ventricular wall thickness to predict full or
      partial pressure reperfusion in ST-elevation acute myocardial infarction.
AB  - Experimental studies have shown that if an acute transmural myocardial infarction
      is reperfused at full pressure there is an immediate and persisting increase in
      end-diastolic wall thickness (EDWT) due to massive intramural edema, with the
      amount of edema inversely related to the residual stenosis in the infarct-related
      artery. This study investigated if these findings are paralleled in the clinical
      setting and whether the resultant myocardial substrate differs after percutaneous
      coronary intervention (PCI) versus thrombolysis (the latter having a higher
      incidence of residual flow limiting stenosis in the culprit vessel). Eighty-eight
      consecutive patients with ST-elevation myocardial infarction were enrolled.
      Twenty-seven patients underwent primary PCI, 23 had rescue PCI, and 38 had
      thrombolysis. Standard M-mode and 2-dimensional echocardiographies were performed
      within 12 hours. Regional EDWT was measured in 904 infarct-related segments after
      the different reperfusion strategies and compared with 504 remote noninfarcted
      segments. EDWT of infarct-related segments after primary PCI was significantly
      increased compared with normal segments. At follow-up, after 6 months, EDWT of
      these segments was significantly decreased, indicating transmural infarction.
      EDWT of infarct-related segments after thrombolysis did not differ from that of
      normal segments. After rescue PCI, EDWT of infarct-related segments was
      significantly decreased compared with that of normal segments. In conclusion,
      full-pressure restoration of epicardial blood flow after transmural myocardial
      infarction causes an immediate increase in EDWT, easily detected by
      echocardiography. In contrast, pressure-limiting reperfusion (typical for
      thrombolysis) resultsin normal EDWT. This confirms experimental data that PCI and
      thrombolysis can differ in their resultant myocardial substrate.

PMID- 18638583
TI  - Comparison of value of leads from body surface maps to 12-lead electrocardiogram
      for diagnosis of acute myocardial infarction.
AB  - We aimed to develop 12-lead electrocardiographic (ECG) models testing ST
      elevation criteria with QRST variables and compare their performance with the 80
      lead body surface map (BSM) in detection of acute myocardial infarction (AMI).
      Because the prevalence of non-ST-elevation AMI is increasing worldwide, advances
      in early ECG detection of AMI are urgently needed. The study population was 755
      consecutive patients presenting with ischemic chest pain from January 2002 to
      June 2004. All patients had electrocardiography and body surface mapping
      performed at initial presentation. AMI occurred in 519 patients (69%, cardiac
      troponin T or I level > or =0.1 ng/ml). Of these 519 patients, 303 (58%) had no
      ST-elevation on the initial 12-lead electrocardiogram. Ten patients were
      classified as having an "aborted AMI" and were included in the AMI analysis. The
      American College of Cardiology/European Society of Cardiology criteria for ST
      elevation on 12-lead electrocardiogram identified 236 patients with AMI
      (sensitivity 45%, specificity 92%). Additional QRST features improved sensitivity
      (51% to 68%) but with decreased specificity (71% to 89%), with the optimal
      multivariate ECG model having a c-statistic of 0.75. The optimal BSM model
      identified 402 patients as having AMI (sensitivity 76%, specificity 92%, c
      statistic 0.84). This improvement in sensitivity over the 12-lead
      electrocardiogram was due mainly to detection of ST-elevation in the high right
      anterior, posterior, and right ventricular territories and AMI in the presence of
      left bundle branch block. In conclusion, QRST variables added to criteria for ST
      elevation result in improvement in sensitivity of the 12-lead electrocardiogram,
      although with decreased specificity. The BSM is superior in detecting AMI and
      demonstrates the importance of electroanatomic evaluation of patients with acute
      coronary syndromes.

PMID- 18638584
TI  - Effectiveness of anemia and chronic kidney disease as predictors for presence and
      severity of coronary artery disease in patients undergoing stress myocardial
      perfusion study.
AB  - Chronic kidney disease (CKD) and anemia portend a higher risk of cardiac events
      and mortality. We sought to ascertain whether coronary artery disease (CAD) by
      myocardial perfusion single-photon emission computed tomography is more common in
      patients with CKD (glomerular filtration rate < or =60 ml/min/1.73 kg/m(2))
      and/or anemia (hemoglobin level < or =13 g/L) and the impact of different degrees
      of CKD. One thousand five hundred eighty patients (mean age 65 +/- 10 years)
      underwent gated myocardial perfusion single-photon emission computed tomography
      and clinical evaluation. Patients were divided into 4 groups (group 1, no
      anemia/no CKD, n = 800; group 2, anemia/no CKD, n = 195; group 3, CKD/no anemia,
      n = 332; group 4, anemia/CKD, n = 253). Multivariate logistic regression analysis
      was undertaken to examine the association of these diagnoses with abnormal
      myocardial perfusion single-photon emission computed tomogram. Compared with
      patients with neither diagnosis, an abnormal scan was more common in those with
      anemia or CKD. Patients with anemia and CKD exhibited more severe CAD (mean
      summed stress score 6.8 vs 4.7, p <0.01). Established high-risk findings were
      more prevalent in patients with anemia and/or CKD, including a summed stress
      score > or =8, transient ischemic dilation, or a left ventricular ejection
      fraction < or =40% (group 1 28%, group 2 38%, group 3 38%, group 4 48%, all p
      values <0.01). Patients with moderate CKD demonstrated an increased risk of an
      abnormal scan (odds ratio 2.66, p <0.0001). After adjustment in multivariate
      analysis, anemia and CKD each remained predictors for an abnormal scan. The
      association was stronger in those with the 2 conditions (odds ratio for high-risk
      scan 1.89, p = 0.0002). In conclusion, in patients with suspected CAD, anemia and
      CKD are predictors of myocardial perfusion single-photon emission computed
      tomographic markers for worsened outcomes. The relation was independent of other
      risk factors, supporting the inclusion of anemia and CKD in global risk
      assessment for patients with suspected CAD.

PMID- 18638585
TI  - Comparison of assessment of native coronary arteries by standard versus three
      dimensional coronary angiography.
AB  - Vessel foreshortening is a major limitation of standard coronary angiography due
      to the 2-dimensional representation of 3-dimensional structures. Three
      dimensional models may overcome it. The aim of this study was to compare
      measurements of coronary segments from quantitative coronary angiography (QCA) in
      an operator-selected "working view" of standard 2-dimensional coronary
      angiography with those from 3-dimensional coronary angiography (3D-CA)
      reconstruction models, which are automatically generated from software applied to
      rotational coronary angiographic acquisitions. Patients who underwent
      percutaneous coronary intervention were considered. Two or 3 segments of the
      artery needing treatment were prespecified, using bifurcations as edges. The
      operator selected a working view from standard angiography as the view best
      representing each segment. Rotational angiography was performed, allowing 3
      dimensional reconstruction of the selected segments. Additionally a marker
      guidewire (with 4 markers 10 mm away from one another at the distal tip) was used
      to further measure segment length, and it was considered the "gold standard"
      reference. In 36 patients, 81 segments from 12 left anterior descending, 12
      circumflex, and 12 right coronary arteries were evaluated. Three-dimensional
      coronary angiography was always feasible. Although reference vessel diameter was
      not different between 3D-CA and QCA (p >0.05), segment length measurements were
      on average 2.3 +/- 2.5 mm longer with 3D-CA than with QCA (p <0.001) and 0.4 +/-
      1.8 mm longer than with marker guidewire measurement (p = 0.047). Marker
      guidewire measurements were 1.9 +/- 2.8 mm longer than QCA measurements (p
      <0.001). According to Bland-Altman plots, 3D-CA and marker guidewire measurements
      had the best agreement. In conclusion, 3-dimensional coronary modeling is highly
      feasible and yields more accurate assessments of the lengths of coronary segments
      than standard QCA.

PMID- 18638586
TI  - Usefulness of microvolt T-wave alternans to predict outcomes in patients with
      ischemic cardiomyopathy beyond one year.
AB  - Previous studies have demonstrated that microvolt T-wave alternans (MTWA)
      screening effectively risk-stratifies patients with ischemic cardiomyopathy.
      Whether the prognostic utility of MTWA diminishes over 3 years of follow-up
      remains unknown. In this study, a prospective cohort of 768 patients with
      ischemic cardiomyopathy (left ventricular ejection fraction <35%) and no previous
      sustained ventricular arrhythmia was developed, of whom 514 (67%) screened MTWA
      nonnegative (positive and indeterminate). The mean follow-up period was 18 +/- 11
      months. The primary end point was all-cause mortality and appropriate implantable
      cardioverter-defibrillator shocks. Stratified Cox regression analyses (by
      implantable cardioverter-defibrillator status) estimated the predictive power of
      MTWA within each year of follow-up and determined whether this diminished over
      time. There were 99 deaths (MTWA negative: 21 [8.3%]; MTWA nonnegative: 78
      [15.2%]) and 33 appropriate implantable cardioverter-defibrillator shocks (MTWA
      negative: 3 [4.0%]; MTWA nonnegative: 30 [9.5%]). After multivariate adjustment,
      a nonnegative MTWA test result was associated with a greater than twofold
      increased risk for events in each of the 3 years of follow-up (year 1: stratified
      hazard ratio 2.19, 95% confidence interval 1.10 to 4.34, p = 0.03; year 2:
      stratified hazard ratio 3.36, 95% confidence interval 1.28 to 8.83, p = 0.01;
      year 3: stratified hazard ratio 2.06, 95% confidence interval 0.81 to 5.22, p =
      0.13). There were no significant interactions between the time periods (year 1 vs
      year 2: p = 0.47; year 1 vs year 3: p = 0.92). In conclusion, MTWA reliably and
      consistently predicts mortality and arrhythmic risk throughout the first 2 to 3
      years of follow-up. Although these findings need further validation, they suggest
      that rescreening with MTWA may not need to be performed more frequently than once
      every 2 years.

PMID- 18638587
TI  - Body weight limitations of United States cardiac catheterization laboratories
      including restricted access for the morbidly obese.
AB  - A telephone survey was performed to determine the current weight limits of
      cardiovascular catheterization laboratories (n = 94) in the United States. The
      minimum, mean, and maximum weight limits of the catheterization laboratories in
      this survey were 160, 198.9, and 250 kg (350, 437.5, and 550 lb), respectively.
      Twenty-two percent of respondents (n = 21) referred to other institutions when
      asked what they did when patients were too heavy, and 70% of respondents (n = 66)
      could not provide an answer. In this population, 5.2 +/- 3.4
      patients/hospital/year were rejected for being over the weight limit. In
      conclusion, these results provide useful information for the future management of
      this growing population.

PMID- 18638588
TI  - Bivalirudin with provisional glycoprotein IIb/IIIa inhibitors in patients
      undergoing primary angioplasty in the setting of cardiogenic shock.
AB  - In patients undergoing percutaneous coronary intervention (PCI), clinical trials
      have demonstrated that the use of bivalirudin with provisional glycoprotein
      IIb/IIIa inhibitors is not inferior to heparin with systematic glycoprotein
      IIb/IIIa inhibitors on major adverse cardiac events and is associated with lower
      rates of bleeding in various clinical settings. Patients with cardiogenic shock
      (CS), however, have been excluded from all pivotal trials. A retrospective
      analysis of 86 consecutive patients undergoing PCI for acute myocardial
      infarction complicated by CS in our center from April 2003 to September 2007 was
      performed. In-hospital death, major adverse cardiac events, and bleeding rates
      were compared in 37 patients who received bivalirudin with or without
      glycoprotein IIb/IIIa inhibitors and 49 patients who were treated with heparin
      and glycoprotein IIb/IIIa inhibitors as anticoagulation management. Baseline
      demographic, clinical, and biological characteristics were similar in the 2
      groups. The in-hospital death rate was significantly lower in the bivalirudin
      group (5.4 vs 32.7%, p = 0.002). There were no differences in the rate of major
      hematoma between the bivalirudin group and the heparin group (3 vs 2.6%, p =
      0.46). In conclusion, bivalirudin with provisional use of glycoprotein IIb/IIIa
      inhibitors appears to be a safe and effective anticoagualtion strategy in
      patients undergoing primary PCI for acute myocardial infarction complicated by
      CS.

PMID- 18638589
TI  - Two-year outcome of patients treated with sirolimus- versus paclitaxel-eluting
      stents in an unselected population with coronary artery disease (from the REWARDS
      Registry).
AB  - Multiple studies comparing sirolimus-eluting stents (SES) and paclitaxel-eluting
      stents (PES) in patients with coronary artery disease have been performed.
      Despite these comparisons, it remains uncertain whether a differential in long
      term efficacy and safety exists. Unselected patients treated exclusively with 1
      drug-eluting stent type were enrolled in the Registry Experience at the
      Washington Hospital Center with Drug-Eluting Stents. There were 2,099 patients
      (3,766 lesions) treated with SES and 1,079 patients (1,850 lesions) treated with
      PES. Patients were followed at 30 days, 1 year, and 2 years for the clinical
      endpoints of death, myocardial infarction, target vessel revascularization, and
      definite and definite/probable stent thrombosis. Patients in the SES group had
      more dyslipidemia, history of congestive heart failure, and ostial lesions;
      patients treated with PES had more previous coronary artery bypass surgery,
      unstable angina, and type C lesions. At 2 years, unadjusted major adverse cardiac
      events (MACE) (22.6% vs 21.1%, p = 0.3) and target vessel revascularization
      (13.3% vs 11.2%, p = 0.1) were comparable. The incidence of definite stent
      thrombosis was higher in the SES group (1.8% vs 0.9%, p = 0.05) driven by early
      events. Similar results were seen after adjustment for baseline differences: MACE
      (hazard ratio 1.1, 95% confidence interval [CI] 0.9 to 1.3, p = 0.5), definite
      stent thrombosis (hazard ratio 2.3, 95% CI 1.0 to 5.2, p = 0.05), and target
      vessel revascularization (hazard ratio 1.1, 95% CI 0.9 to 1.4, p = 0.4). The
      incidence and rate of late stent thrombosis (>30 days) were similar (0.7% vs
      0.5%, p = 0.4 and 0.24%/year, both groups, respectively). In conclusion, no major
      differential in long-term safety or efficacy was detected between SES and PES;
      both stent types were efficacious in reducing revascularization but were limited
      by a small continual increase in late stent thrombosis.

PMID- 18638590
TI  - Observations and outcomes of definite and probable drug-eluting stent thrombosis
      seen at a single hospital in a four-year period.
AB  - Stent thrombosis (ST) is a major safety concern after drug-eluting stent (DES)
      deployment, resulting in significant morbidity and mortality. The goal of this
      study was to examine the incidence, timing, clinical correlates, and outcomes
      after DES thrombosis in a real-world population. A retrospective analysis of
      8,402 patients who underwent percutaneous coronary intervention and received a
      DES was performed. After DES implantation, 84 definite (DST) and 127 probable ST
      events occurred. The incidence of early DST was 0.8%, late DST was 0.4%, and very
      late DST was 0.4%. Multivariate analysis showed that a history of diabetes
      mellitus, myocardial infarction during admission, number of stents, and DES
      placement in a restenotic lesion were independently associated with DST. The
      incidence of early definite or probable ST (DPST) was 1.9%, late DPST was 1.4%,
      and very late DPST was 0.7%. Multivariate analysis showed that a history of
      diabetes, myocardial infarction during admission, cardiogenic shock, number of
      stents, and DES use in a restenotic lesion were independently associated with
      DPST. Both types of ST were associated with significantly higher rates of all
      cause death, Q-wave myocardial infarction, and revascularization up to 24 months
      after DES implantation. In conclusion, ST after DES implantation in contemporary
      practice continues to occur from 30 days to 2 years at a rate > or =0.36%/year
      and is associated with high rates of morbidity and mortality. Diabetes mellitus,
      myocardial infarction, and DES use in a restenotic lesion were strongly
      associated with DST; therefore, careful consideration should apply when deploying
      a DES in these populations.

PMID- 18638591
TI  - Intravascular ultrasound evaluation of optimal drug-eluting stent expansion after
      poststent balloon dilation using a noncompliant balloon versus a semicompliant
      balloon (from the Poststent Optimal Stent Expansion Trial [POET]).
AB  - The impact of type of balloon such as noncompliant (NC; Quantum) or semicompliant
      (SC; Maverick(2)) used after stent dilation on optimal stent expansion (OSE) has
      not been established for drug-eluting stents (DESs). We conducted a prospective
      multicenter, randomized study to compare NC with SC balloons after stent balloon
      dilatation. A total of 301 patients (127 men, 83 women, 62 +/- 9 years of age)
      treated with a DES (sirolimus-eluting stent [SES], n = 152; paclitaxel-eluting
      stent, n = 149) were included. OSE followed the definition of the Multicenter
      Ultrasound Stenting in Coronaries (MUSIC) study. The primary end point was the
      incidence of OSE using intravascular ultrasound according to type of balloon.
      Baseline characteristics of each group showed no significant differences. OSE in
      the SC balloon group was achieved at higher rates than the NC balloon group (53
      +/- 35%, vs 73 +/- 48%, p = 0.022 in all stents; 25 +/- 33%, vs 36, 48%, p =
      0.051 in SESs). However, any differences in the achievement of OSE between the NC
      and SC balloon groups were not present in paclitaxel-eluting stents. In
      conclusion, despite postadjuvant balloon inflations with high pressures,
      underexpansion of the DES was seen commonly. Between the 2 types of balloon for
      adjuvant dilation after DES implantation, same-size SC balloons could be more
      useful for obtaining OSE than NC balloons, especially in SESs.

PMID- 18638592
TI  - Angiographic patterns of drug-eluting stent restenosis and one-year outcomes
      after treatment with repeated percutaneous coronary intervention.
AB  - Patterns of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation
      and outcomes after treatment have not been studied systematically in all comers.
      We compared patterns of ISR and outcomes of repeated percutaneous coronary
      intervention in consecutive patients with DES-ISR. A total of 137 patients with
      182 lesions underwent repeated percutaneous coronary intervention for DES-ISR at
      Columbia University Medical Center from August 2004 to April 2006. DES-ISR was
      treated with repeated DES placement in 84% of patients and balloon angioplasty in
      16%. There was 1 stent thrombosis at 30 days, and at 1 year, major adverse
      cardiac events occurred in 10% of patients, driven primarily by an 8% rate of
      target-lesion revascularization. After exclusion of 12 patients with multiple ISR
      lesions, data were further analyzed from 125 patients with 152 DES-ISR lesions,
      of which 118 were originally treated with sirolimus-eluting stents and 34 were
      treated with paclitaxel-eluting stents (PES-ISR). Baseline features were well
      matched between the 2 groups, except that patients with PES-ISR were older. A
      focal pattern of ISR was observed in 69.5% of patients overall. However, patients
      originally treated with a PES had a significantly higher frequency of diffuse
      intrastent ISR in comparison with sirolimus-eluting stent ISR (30.3% vs 13.6%, p
      = 0.03). In conclusion, the pattern of ISR in most DES-ISR in this unselected
      patient population was focal, with higher rates of diffuse intrastent restenosis
      seen with PES-ISR. Treatment with either repeated DES implantation or balloon
      angioplasty for DES-ISR was safe and associated with low overall rates of target
      lesion revascularization and major adverse cardiac events at 1 year.

PMID- 18638593
TI  - Association of coronary atherosclerosis detected by multislice computed
      tomography and traditional risk-factor assessment.
AB  - Framingham risk score is an office-based tool used for long-term coronary heart
      disease risk stratification. Most acute coronary events occur in association with
      proximal nonobstructive atherosclerotic plaque. Multislice computed tomography
      detects both obstructive coronary artery disease (CAD) and proximal
      atherosclerotic plaque with high accuracy. The association of Framingham risk
      score with obstructive CAD and proximal atherosclerotic plaque was tested.
      Coronary multislice computed tomography was performed in 295 patients (61% men,
      mean age 54 +/- 13 years) without documented CAD referred for evaluation of
      cardiac symptoms. Framingham risk score was computed and patients were stratified
      according to 10-year risk (n = 213 [72%] low, n = 74 [25%] intermediate, and n =
      8 [3%] high). Obstructive CAD was defined as > or =50% stenosis in > or =1
      epicardial coronary artery. Proximal atherosclerotic plaque was defined as
      calcified or noncalcified plaque in the left main or proximal left anterior
      descending artery. In the low- and intermediate-Framingham risk score groups,
      there was a high frequency of proximal atherosclerotic plaque (44% and 75%) and
      obstructive CAD (16% and 34%), although both findings were more prevalent in the
      high-Framingham risk score group (63% for atherosclerotic plaque, 88% for
      obstructive CAD), respectively. Proximal atherosclerotic plaque was noncalcified
      in approximately 13 of patients. In women (n = 114) and younger (<55 years)
      patients (n = 148), most (93% and 91%, respectively) had a low Framingham risk
      score. There were 48 women and 51 younger patients with proximal atherosclerotic
      plaque, of whom only 40% (in each group) were on statin therapy. In conclusion,
      of patients with a low and intermediate Framingham risk score, a significant
      proportion had proximal atherosclerotic plaque or obstructive CAD.

PMID- 18638594
TI  - Comparison effect of atorvastatin (10 versus 80 mg) on biomarkers of inflammation
      and oxidative stress in subjects with metabolic syndrome.
AB  - Metabolic syndrome (MS), characterized by low-grade inflammation, confers an
      increased risk for cardiovascular disease. Statins, in addition to having lipid
      lowering effects, have pleiotropic effects and decrease biomarkers of
      inflammation and oxidative stress. The Treating to New Target Study showed a
      greater decrease in low-density lipoprotein (LDL) cholesterol and cardiovascular
      events with atorvastatin 80 mg versus 10 mg in patients with MS with coronary
      heart disease. However, part of this benefit could be caused by the greater
      pleiotropic effects of the higher dose of atorvastatin. The dose-response effect
      of atorvastatin on biomarkers of inflammation and oxidative stress has not been
      investigated in subjects with MS. Thus, the dose-response effect of atorvastatin
      on biomarkers of inflammation (high-sensitivity C-reactive protein [hs-CRP],
      matrix metalloproteinase-9, and nuclear factor-kappaB [NF-kB] activity) and
      oxidative stress (oxidized LDL, urinary nitrotyrosine, F2-isoprostanes, and
      monocyte superoxide release) was tested in a randomized double-blind clinical
      trial in subjects with MS. Seventy subjects were randomly assigned to receive
      placebo or atorvastatin 10 or 80 mg/day for 12 weeks. A strong dose-response
      (atorvastatin 10 compared with 80 mg, p <0.05) was observed for changes in total,
      LDL (32% and 44% reduction), non-high-density lipoprotein (28% and 40%
      reduction), and oxidized LDL cholesterol (24% and 39% reduction) at atorvastatin
      10 and 80 mg, respectively. Hs-CRP, matrix metalloproteinase-9, and NF-kB
      significantly decreased in the 80-mg atorvastatin group compared with baseline.
      In conclusion, this randomized trial of subjects with MS showed the superiority
      of atorvastatin 80 mg compared with its 10-mg dose in decreasing oxidized LDL, hs
      CRP, matrix metalloproteinase-9, and NF-kB activity.

PMID- 18638595
TI  - Aldosterone synthase gene polymorphism as a determinant of atrial fibrillation in
      patients with heart failure.
AB  - We analyzed the possible association between aldosterone synthase (CYP11B2) T
      344C polymorphism, which is associated with increased aldosterone activity, and
      the prevalence of atrial fibrillation (AF) in 196 consecutive patients who had
      symptomatic systolic heart failure (HF; left ventricular ejection fraction <40%)
      for > or =3 months before recruitment. Genomic DNA was extracted from peripheral
      blood leukocytes using a standard protocol. Subjects were genotyped for the
      CYP11B2 polymorphism using the polymerase chain reaction/restriction fragment
      length polymorphism approach. AF was present in 63 patients (33%) with HF. We
      found the -344 CC genotype to be a strong independent marker for AF. Almost 1/2
      (45%) of patients with this genotype had AF compared with 1/4 (27%) with -344 TT
      and TC genotypes (p = 0.01). A multivariate stepwise logistic regression model
      that included age, gender, New York Heart Association class, CYP11B2 -344CC
      genotype, and echocardiographic measurements of left ventricular ejection
      fraction, left atrial dimension, left ventricular end-diastolic diameter, and
      mitral regurgitation severity showed that the CYP11B2 CC genotype (adjusted for
      age and left atrial size) was an independent predictor of AF (adjusted odds ratio
      2.35, 95% confidence interval 1.57 to 3.51, p = 0.03). In conclusion, CYP11B2 T
      344C promoter polymorphism predisposes to clinical AF in patients with HF.

PMID- 18638596
TI  - Anatomic approach for ganglionic plexi ablation in patients with paroxysmal
      atrial fibrillation.
AB  - There is evidence that parasympathetic denervation may prevent atrial
      fibrillation (AF) recurrences. This study aimed at applying an anatomic approach
      for ablation of atrial ganglionic plexi (GPs) in patients with paroxysmal AF.
      Nineteen patients with symptomatic, paroxysmal AF underwent anatomically guided
      radiofrequency ablation at the location of the 4 main left atrial GPs and were
      prospectively assessed for recurrence of AF or other atrial arrhythmia. This
      group was compared with 19 age- and gender-matched patients who previously
      underwent conventional circumferential pulmonary vein ablation. All ablation
      procedures were uneventful. Circumferential and GP ablations were accomplished
      with a radiofrequency delivery time of 28 +/- 5 versus 18 +/- 3 min (p <0.001)
      and a fluoroscopy time of 31 +/- 5 versus 18 +/- 5 min (p <0.001), respectively.
      Parasympathetic reflexes during radiofrequency ablation were elicited in 4
      patients (21%). Arrhythmia recurred in 7 patients (37%) with circumferential
      ablation and 14 patients (74%) with GP ablation, during 1-year follow-up (p for
      log-rank test = 0.017). In 2 patients with GP ablation, left atrial flutters were
      documented in addition to AF during follow-up. Patients who underwent GP ablation
      had an almost 2.5 times higher risk of AF recurrence compared with those who
      underwent circumferential ablation (hazard ratio 2.6, 95% confidence interval 1.0
      to 6.6, p = 0.038). In conclusion, anatomically guided GP ablation is feasible
      and safe in the electrophysiology laboratory, but this approach yields inferior
      clinical results compared with circumferential ablation.

PMID- 18638597
TI  - Relation between left ventricular regional radial function and radial wall motion
      abnormalities using two-dimensional speckle tracking in children with idiopathic
      dilated cardiomyopathy.
AB  - Left ventricular (LV) regional radial function and its relation to radial wall
      motion abnormalities have not been investigated in children with idiopathic
      dilated cardiomyopathy (IDC). Radial strain was measured using 2-dimensional
      speckle tracking to evaluate regional radial function and wall motion in 6 LV
      segments in 24 children (0 to 18 years old) with IDC and 16 healthy controls.
      Patients and controls were similar in age. Patients with IDC had higher heart
      rates (97 +/- 28 vs 77 +/- 19, p <0.05) and decreased ejection fraction (34 +/-
      12% vs 66 +/- 7%, p <0.0001) compared with controls. Radial strain in all
      segments was significantly lower in patients with IDC. In IDC, average radial
      strain correlated well with ejection fraction (r = 0.8, p <0.0001). The SD of
      time to peak radial strain among 6 LV segments was significantly higher in
      patients with IDC than in controls (56 +/- 38 vs 15 +/- 12 ms, p <0.0001).
      Segmental peak radial strain correlated closely to time to peak radial strain in
      controls (r = 0.98, p = 0.0008), but less in patients with IDC (r = 0.76, p =
      0.07). In conclusion, LV regional radial function is impaired in pediatric IDC,
      in association with increased radial dyssynchrony, revealing a possible important
      mechanism for LV dysfunction in these children.

PMID- 18638598
TI  - Frequency of severe pulmonary hypertension complicating "isolated" atrial septal
      defect in infancy.
AB  - Atrial septal defects (ASDs) are typically asymptomatic in infancy and early
      childhood, and elective defect closure is usually performed at ages of 4 to 6
      years. Severe pulmonary hypertension (PH) complicating an ASD is seen in
      adulthood and has only occasionally been reported in small children. A
      retrospective study was undertaken to evaluate the incidence of severe PH
      complicating an isolated ASD and requiring early surgical correction. During a 10
      year period (1996 to 2006), 355 pediatric patients underwent treatment for
      isolated ASDs either surgically or by catheter intervention at 2 tertiary
      referral centers. Two hundred ninety-seven patients had secundum ASDs, and 58 had
      primum ASDs with mild to moderate mitral regurgitation. Eight infants were found
      with isolated ASDs (6 with secundum ASDs and 2 with primum ASDs) associated with
      significant PH, accounting for 2.2% of all patients with ASDs at the centers.
      These 8 infants had invasively measured pulmonary artery pressures of 50% to 100%
      of systemic pressure. They were operated in the first year of life and had
      complicated postoperative courses requiring specific treatment for PH for up to
      16 weeks postoperatively. The ultimate outcomes in all 8 infants were good, with
      persistent normalization of pulmonary pressures during midterm follow-up of up to
      60 months (median 28). All other patients with ASDs had normal pulmonary
      pressures, and the mean age at defect closure was significantly older, at 6.2
      years for secundum ASDs and 3.2 years for primum ASDs. In conclusion, ASDs were
      rarely associated with significant PH in infancy but then required early surgery
      and were associated with excellent midterm outcomes in these patients.

PMID- 18638599
TI  - Comparison of National Football League linemen versus nonlinemen of left
      ventricular mass and left atrial size.
AB  - Retired National Football League (NFL) linemen have higher cardiovascular
      mortality compared with nonlinemen. We examined echocardiographic characteristics
      of retired NFL linemen compared with nonlinemen to determine if position
      dependent cardiac remodeling resulted in increased left ventricular (LV) mass and
      left atrial (LA) size. We performed echocardiography in 487 retired NFL football
      players. Demographic, medical, and professional career information was collected.
      Interventricular septal and posterior wall thickness, LV end diastolic diameter,
      and LA area were measured. Body mass index (BMI) and LV mass were calculated.
      Retired linemen had significantly higher LV mass (234.8 +/- 65.8 g) than
      nonlinemen (199.8 +/- 55.4 g, p <0.0001). LA area was higher in linemen versus
      nonlinemen (22.5 vs 20.1 cm(2), p <0.0001). Independent predictors of increased
      LV mass were BMI (p <0.003), linemen position (p <0.024), and systolic blood
      pressure (p <0.005). In former players with BMI <35 kg/m(2) there was a
      difference between linemen and nonlinemen in LV mass (219.9 +/- 44.3 vs 182.6 +/-
      44.3 g, p = 0.004) and LV mass/height (114.3 +/- 23.5 vs 98.8 +/- 25.2 g/m, p =
      0.005). In former players with BMI >35 kg/m(2), there was no difference. There
      was no difference in LA area between linemen and nonlinemen in both BMI groups.
      In conclusion, LV mass and LA area size were highest in retired linemen. Player
      BMI, position, and systolic blood pressure were significant predictors of LV
      mass. In retired linemen compared with retired nonlinemen, the persistence of
      these cardiac adaptations may contribute to the higher cardiovascular mortality
      seen in retired linemen.

PMID- 18638600
TI  - Relation of endothelial function to cardiovascular risk in women with sedentary
      occupations and without known cardiovascular disease.
AB  - Our purpose was to determine predictors of endothelial function and potential
      association with cardiovascular risk in women with sedentary occupations, in whom
      obesity-associated risk factors may contribute to excess morbidity and mortality.
      Ninety consecutive women (age range 22 to 63 years, 22 overweight (body mass
      index [BMI] > or =25 to 29.9 kg/m(2)) and 42 obese (BMI > or = 30 kg/m(2)), had
      vital signs, lipids, insulin, glucose, high-sensitivity C-reactive protein, and
      sex hormones measured. Endothelial function was determined using brachial artery
      flow-mediated dilation after 5 minutes of forearm ischemia. Treadmill stress
      testing was performed with gas exchange analysis at peak exercise (peak oxygen
      consumption [Vo(2)]) to assess cardiorespiratory fitness. Brachial artery
      reactivity was negatively associated with Framingham risk score (r = -0.3542, p =
      0.0007). Univariate predictors of endothelial function included peak Vo(2) (r =
      0.4483, p <0.0001), age (r = -0.3420, p = 0.0010), BMI (r = -0.3065, p = 0.0035),
      and high-sensitivity C-reactive protein (r = -0.2220, p = 0.0400). Using multiple
      linear regression analysis with stepwise modeling, peak Vo(2) (p = 0.0003) was
      the best independent predictor of brachial artery reactivity, with age as the
      only other variable reaching statistical significance (p = 0.0436) in this model.
      In conclusion, endothelial function was significantly associated with
      cardiovascular risk in women with sedentary occupations, who were commonly
      overweight or obese. Even in the absence of routine exercise, cardiorespiratory
      fitness, rather than conventional risk factors or body mass, is the dominant
      predictor of endothelial function and suggests a modifiable approach to risk.

PMID- 18638601
TI  - Incidence of contrast-induced nephropathy in patients with chronic renal
      insufficiency undergoing multidetector computed tomographic angiography treated
      with preventive measures.
AB  - Contrast-induced nephropathy (CIN) is associated with adverse outcomes.
      Strategies for its prevention have been evaluated for patients undergoing
      invasive coronary and peripheral angiography, including treatment with N
      acetylcysteine, sodium bicarbonate, and use of iso-osmolar nonionic contrast.
      Recently, multidetector computed tomographic angiography (MDCTA) of the coronary
      and peripheral arteries has been introduced as an accurate method for assessing
      vascular stenosis and has been widely adopted for assessment of outpatients with
      suspected coronary artery disease or peripheral arterial disease. To date, the
      incidence of CIN in outpatients with chronic renal insufficiency (CRI) treated
      with CIN-preventive strategies undergoing MDCTA remains unknown. Thus, we
      evaluated the incidence of CIN in outpatients with CRI (creatinine 1.5 to 2.5
      mg/dl) undergoing MDCTA using CIN-preventive measures; 400 patients with CRI
      (78.5% men, mean age 76 years, 41% with diabetes) underwent MDCTA with iodixanol
      for detection of coronary artery disease or peripheral arterial disease (mean
      contrast volume 101 cc). CIN was defined as a nonallergic creatinine increase of
      >0.5 mg/dl. Creatinine levels were obtained before and 3 to 5 days after MDCTA;
      the average creatinine levels were 1.80 mg/dl and 1.75 mg/dl, respectively (p =
      NS), with an average change of -0.03 mg/dl. In the study cohort, only 7 patients
      (1.75%) experienced a creatinine increase >0.5 mg/dl, satisfying the definition
      of CIN. In conclusion, multivariate analysis, diabetes was the only predictor for
      CIN (odds ratio 5.9, 95% confidence interval 1.0 to 33.3, p = 0.045). No patient
      required hemodialysis. In conclusion, in patients with CRI undergoing MDCTA and
      receiving CIN-preventive measures, the incidence of CIN is low.

PMID- 18638602
TI  - Comparison of usefulness of tissue Doppler imaging versus brain natriuretic
      peptide for differentiation of constrictive pericardial disease from restrictive
      cardiomyopathy.
AB  - Brain (B-type) natriuretic peptide (BNP) and tissue Doppler imaging may
      distinguish restrictive cardiomyopathy (RCMP) from idiopathic constrictive
      pericardial disease (CP). However, their comparative efficacy is unknown for
      patients with CP from secondary causes (e.g., surgery or radiotherapy). We
      compared the efficacy of tissue Doppler imaging and BNP for differentiation of
      RCMP (n = 15) and CP (n = 16) were compared. BNP was higher in patients with RCMP
      than CP (p = 0.008), but the groups overlapped, particularly for BNP <400 pg/ml.
      BNP was lower with idiopathic CP than secondary CP (139 +/- 50 vs 293 +/- 69
      pg/ml; p <0.001) or RCMP (139 +/- 50 vs 595 +/- 499 pg/ml; p <0.001), but not
      significantly different between those with secondary CP and RCMP (293 +/- 69 vs
      595 +/- 499 pg/ml; p = 0.1). Patients with CP and RCMP had less overlap in early
      diastolic and isovolumic contraction tissue Doppler imaging velocities compared
      with BNP, with clear separation of groups evident with mean early diastolic
      annular velocities (averaged from 4 walls). Early diastolic tissue Doppler
      imaging velocity was superior to BNP for differentiation of CP and RCMP (area
      under the curve 0.97 vs 0.76, respectively; p = 0.01). In conclusion, mean early
      diastolic mitral annular velocity correctly distinguished CP from RCMP even when
      there was a large overlap of BNP between the 2 groups.

PMID- 18638603
TI  - Relation between iron-overload indices, cardiac echo-Doppler, and biochemical
      markers in thalassemia intermedia.
AB  - Cardiovascular impairment is a major cause of morbidity and mortality in patients
      with thalassemia intermedia. In this study, echocardiographic assessment of left
      heart condition was performed in patients with thalassemia intermedia, and its
      relation to hematologic variables--amino terminal pro-brain natriuretic peptide
      (NT-proBNP), ferritin, hemoglobin--and liver iron concentration (LIC) was
      investigated. Echocardiographic assessment was performed using pulse-wave Doppler
      and tissue Doppler imaging. Data from 74 patients with thalassemia intermedia--35
      men, 39 women, mean age 26.5 years (8 to 63)--were randomly selected and
      evaluated. Blood samples were collected for NT-proBNP levels in a random subgroup
      of 19 patients. Mean baseline values were hemoglobin 8.4 g/dl (4.9 to 13.1),
      serum ferritin 902.6 ng/ml (15 to 4,140), LIC 9.0 mg Fe/g (0.5 to 32.1), and NT
      proBNP 113.5 pg/ml (16.4 to 371). Correlation between LIC and pulmonary artery
      systolic pressure was significant, suggesting that iron loading in the liver is
      indicative of cardiovascular sequelae. NT-proBNP was significantly correlated
      with the ratio of the left ventricular early rapid filling wave to early
      diastolic velocity at the mitral annulus (r = 0.50, p = 0.04) and hemoglobin (r =
      -0.49, p = 0.03), but not with other characteristics assessed. In conclusion,
      this study has highlighted the importance of using tissue Doppler imaging rather
      than pulse-wave Doppler to characterize left ventricular diastolic dysfunction in
      patients with thalassemia intermedia. Demonstration of the correlation of LIC and
      pulmonary artery systolic pressure independent of left ventricular filling
      pressures supports our hypothesis that left ventricular diastolic dysfunction
      does not contribute to the increased pulmonary artery systolic pressure in
      patients with thalassemia intermedia.

PMID- 18638604
TI  - Enhanced hype.
AB  - The recently published Effect of Combination Ezetimibe and High-Dose Simvastatin
      vs. Simvastatin Alone on the Atherosclerotic Process in Patients With
      Heterozygous Familial Hypercholesterolemia (ENHANCE) trial seems to raise
      questions regarding the notion that lipid lowering is of benefit in the
      prevention and treatment of vascular disease. Before one can make this
      conclusion, a careful analysis of the trial, including the subjects included and
      the surrogate end point studied, is required. The results of this study should be
      taken in context with those of many other studies showing that lipid lowering by
      many approaches is beneficial. In conclusion, the public fury over this study,
      with physicians making unsupported statements to the press and on the Web, is
      unfortunate and should be discouraged in the future.

PMID- 18638605
TI  - Aortic distensibility in patients with bicuspid aortic valves.

PMID- 18638606
TI  - First, remove the offending agent.

PMID- 18638607
TI  - Predicting noninvasively left ventricular filling pressures.

PMID- 18638608
TI  - When to test renal function to disclose contrast-induced nephropathy.

PMID- 18638610
TI  - Treating lipids in the general population.

PMID- 18638611
TI  - Continuity equations.

PMID- 18638612
TI  - Increased cardiovascular risk in patients with human immunodeficiency virus
      infection under highly active antiretroviral therapy.

PMID- 18638613
TI  - Management of hypertension in patients with enhanced cardiovascular risk.
      Introduction.

PMID- 18638614
TI  - Management of hypertension in patients with chronic kidney disease and diabetes
      mellitus.
AB  - Treatment of patients at high risk for developing cardiovascular disease aims at
      controlling blood pressure, optimizing blood glucose levels, and providing
      renoprotection. Chronic kidney disease (CKD) and diabetes mellitus are prevalent
      causes of cardiovascular disease owing to associations with major cardiovascular
      risk factors, such as hypertension, and they are substantial health burdens. Even
      mild-to-moderate CKD and prehypertension increase cardiovascular risk. First-line
      agents for reducing cardiovascular risk are inhibitors of the renin-angiotensin
      system: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
      receptor blockers (ARBs). In clinical trials, treatment of high-risk patients
      with ACE inhibitors and ARBs delays or prevents the onset of diabetes and
      prevents progression of renal disease and cardiovascular events, including
      cardiovascular mortality. Current evidence indicates that the clinical efficacy
      of these end points includes effects that may be beyond blood pressure reduction.

PMID- 18638615
TI  - Relating cardiovascular risk to out-of-office blood pressure and the importance
      of controlling blood pressure 24 hours a day.
AB  - Blood pressure exhibits a natural circadian rhythm characterized by a decrease
      during sleep, then a steep increase in the early morning period followed by
      higher values throughout the active waking period. Because an excessive early
      morning surge in blood pressure is associated with an elevated risk for
      cardiovascular events, it represents a potential therapeutic target in patients
      with hypertension, especially those already at high risk for such events.
      Ambulatory blood pressure monitoring (ABPM) is an out-of-office technique that
      allows assessment of blood pressure control during a 24-hour period, including
      the morning surge. It is known that 24-hour control based on ABPM is a better
      predictor of hypertensive target-organ involvement and cardiovascular events than
      conventional in-office blood pressure measurement. ABPM also reveals that many
      antihypertensive drugs do not adequately control early morning blood pressure,
      particularly when given once daily in the morning. There are several effective
      ways to improve morning blood pressure control. These include using agents with a
      long pharmacologic half-life; prescribing drug formulations specifically designed
      to target the morning blood pressure surge when given at bedtime; or increasing
      dosages to twice daily that of conventional shorter-acting agents.

PMID- 18638616
TI  - Management of hypertension and cerebrovascular disease in the elderly.
AB  - Cardiovascular disease and stroke disproportionately affect the elderly. The risk
      for stroke and transient ischemic attack increases exponentially with age. Blood
      pressure is a potent modifiable target for reducing the risk for stroke in the
      elderly. In elderly patients with isolated systolic hypertension and those with
      intracranial atherosclerotic disease, blood pressure lowering has consistently
      been shown to be well tolerated and effective in reducing the risk for stroke and
      its complications. Evidence suggests that ambulatory blood pressure monitoring
      may provide a more sensitive means of detecting patients at risk and monitoring
      therapeutic effect. Agents that modify the renin-angiotensin system, particularly
      angiotensin receptor blockers, may confer additional benefit in stroke protection
      beyond blood pressure lowering. Several clinical trials currently in progress
      promise to provide guidance regarding the optimal choice of agent and degree of
      blood pressure lowering for prevention of stroke and cognitive decline in elderly
      patients.

PMID- 18638617
TI  - Management of hypertension in patients with cardiac disease: use of renin
      angiotensin blocking agents.
AB  - Inhibition of renin-angiotensin system (RAS) activity using angiotensin
      converting enzyme inhibitors or angiotensin II receptor blockers (ARBs) is
      beneficial in patient populations with left ventricular dysfunction or systolic
      heart failure (HF) and other forms of heart disease. In high-risk patients with
      coronary heart disease (CHD), treatment with these agents reduces the mortality
      rate and improves secondary outcomes. Individuals with stable CHD who are at
      lower risk benefit less from treatment. RAS inhibition also provides some
      clinical benefit to patients with diastolic HF and preserved left ventricular
      function. Left ventricular hypertrophy (LVH) is a strong predictor of
      cardiovascular events and all-cause mortality in patients with hypertension.
      Treatment with an ARB reduces the risk for adverse cardiovascular outcomes in
      patients with hypertension and LVH. The benefits correlate with regression of
      LVH, and the effect is independent of the degree of blood pressure lowering.
      Finally, studies indicate that a history of hypertension in patients who have not
      had a myocardial infarction (MI) increases the risk for HF after MI; the risk is
      decreased in patients with hypertension who receive treatment with a RAS
      inhibitor.

PMID- 18638618
TI  - Bronchiectasis in adults. Foreword.

PMID- 18638619
TI  - Bronchiectasis in adults. Introduction.

PMID- 18638620
TI  - Bronchiectasis: introduction, etiology, and clinical features.

PMID- 18638621
TI  - Diagnostic evaluation of bronchiectasis.

PMID- 18638622
TI  - Management of bronchiectasis.

PMID- 18638623
TI  - Allergic bronchopulmonary aspergillosis.

PMID- 18638624
TI  - Nontuberculous mycobacterium in association with bronchiectasis.

PMID- 18638625
TI  - Bronchiectasis-clinical cases.

PMID- 18638626
TI  - Identification of child maltreatment using prospective and self-report
      methodologies: a comparison of maltreatment incidence and relation to later
      psychopathology.
AB  - OBJECTIVES: One of the greatest methodological problems in the study of childhood
      maltreatment is the discrepancy in methods by which cases of child maltreatment
      are identified. The current study compared incidents of maltreatment identified
      prospectively, retrospectively, or through a combination of both methods. METHOD:
      Within a cohort of 170 participants followed from birth to age 19, incidents of
      maltreatment which occurred prior to age 17.5 were identified via prospective
      case review and interviewer ratings of retrospective self-reports. Multi
      informant measures of behavior problems were obtained at age 16, and diagnostic
      assessments of psychopathology were completed at age 17.5. RESULTS: While the
      maximal number of maltreatment cases was identified by using a combination of all
      available identification methods, the prospective method was the single most
      comprehensive method for identifying the most cases of childhood physical abuse,
      sexual abuse, and neglect. Those who were identified as maltreated by a
      combination of both prospective and self-report methods experienced the greatest
      number of incidences of maltreatment (i.e., 49% of this group experienced more
      than one type of maltreatment) and displayed the most emotional and behavioral
      problems in late adolescence (i.e., 74% met diagnostic criteria for a clinical
      disorder). CONCLUSIONS: This study emphasizes the variability in the incidence
      rates of maltreatment and the psychological outcomes that result from utilizing
      different methods of identification. The most severe cases of maltreatment are
      likely to be identified by both prospective and retrospective methods; however,
      cases that are identified solely through retrospective self-report may have
      unique relations to psychopathology in late adolescence. PRACTICE IMPLICATIONS:
      Reliance on a single method to identify childhood maltreatment incidents often
      overlooks many cases. Comparing both prospective case reviews and retrospective
      self-reports in late adolescence, the most severe cases of multiple incidents of
      abuse were most likely to be identified by both methodologies. The less severe
      maltreatment incidents were more likely to be missed, either by prospective
      methods or, more frequently, by self-report methods. Practitioners must be
      continually sensitive to possible abuse histories among their clients, seeking
      out information from multiple sources whenever feasible. Additionally, the
      potential effects of abuse disclosure on pre-existing or developing
      psychopathology should be considered.

PMID- 18638627
TI  - Kaposi sarcoma: a continuing conundrum.
AB  - Kaposi sarcoma (KS) remains a challenge. Its classic or Mediterranean form tends
      to be benign. In transplant recipients it may be less so. As part of the AIDS
      pandemic, of which it was an original defining component, it may be life
      threatening. It is due to human herpesvirus-8, which is necessary but not
      sufficient to produce the disease. KS has a low prevalence in the general
      population of the United States and United Kingdom, with an intermediate rate in
      Italy and Greece, and a high one in parts of Africa. In Italy, hot spots include
      its southern regions, the Po River Valley, and Sardinia, possibly related to a
      high density of blood-sucking insects. An important challenge is to treat KS
      patients without immunocompromising them. The potential of effective anti-herpes
      virus therapy and the use of sirolimus in transplantation recipients have added
      new opportunities for KS prevention. LEARNING OBJECTIVES: At the conclusion of
      this learning activity, participants should be able to provide the most recent
      information about Kaposi sarcoma in the context in which it occurs. Its classic
      or Mediterranean form, its pattern in transplant recipients and others
      iatrogenically immunosuppressed, and its occurrence as a potentially life
      threatening part of the AIDS pandemic will be stressed. Its etiology and
      transmission will be discussed in detail to facilitate understanding of Kaposi
      sarcoma and of human herpesvirus-8 infection in the general population of the
      United States and United Kingdom, in Italy and Greece, and in certain parts of
      Africa. Its therapy, including the concept of doing it without immunocompromising
      the patient, will be stressed. New opportunities for Kaposi sarcoma prevention
      will also be discussed.

PMID- 18638628
TI  - Prospective evaluation of surgical site infection rate among patients with Mohs
      micrographic surgery without the use of prophylactic antibiotics.
AB  - BACKGROUND: Antibiotics may be indiscriminately given to patients undergoing Mohs
      micrographic surgery (MMS) for the prevention of surgical site infections,
      despite a low risk of infection in these patients. OBJECTIVE: We sought to
      evaluate the rate of wound infections among patients undergoing MMS without the
      use of prophylactic antibiotics. METHODS: We prospectively evaluated 1000
      consecutive patients undergoing MMS for nonmelanoma skin cancer or modified
      MMS/"slow Mohs" for lentigo maligna melanoma in situ. RESULTS: The overall wound
      infection rate among 1000 patients with 1115 tumors was 0.7% (8/1115 tumors).
      Five (62.5%) of 8 infections occurred on the nose with an overall 1.7% (5/302)
      nose infection rate. Seven (87.5%) of 8 infections occurred after flap
      reconstruction with an overall 2.4% (7/296) flap closure infection rate. Four
      (50%) of 8 infections occurred in patients requiring more than one Mohs stage for
      tumor clearance with a 0.8% (4/487) overall infection rate in cases requiring
      multiple Mohs stages. Two (25%) of 8 infections had cultures positive for
      oxacillin-resistant Staphylococcus aureus. No wound infections occurred in cases
      involving the lips or ears, skin-graft closures, or below-knee or modified MMS
      procedures. LIMITATIONS: This was a prospective single institution uncontrolled
      study. CONCLUSION: Rates of infections among patients undergoing MMS or modified
      MMS are exceedingly low. Indiscriminate use of antibiotics increases patient risk
      to adverse drug reactions and antibiotic resistance. Administration of
      antibiotics to patients undergoing MMS should be on a case-by-case basis
      according to the known risk factors combined with clinical judgment.

PMID- 18638629
TI  - Epidermodysplasia verruciformis-associated and genital-mucosal high-risk human
      papillomavirus DNA are prevalent in nevus sebaceus of Jadassohn.
AB  - BACKGROUND: The hamartoma nevus sebaceus (NS) presents at birth or early
      childhood as a yellowish plaque characterized histologically by variable
      acanthosis, papillomatosis, sebaceus hyperplasia, and proliferations of adnexal
      structures. Clinically apparent human papillomavirus (HPV) infection is also
      recognized by acanthosis and papillomatosis. OBJECTIVE: We sought to determine
      the prevalence and physical state of HPV DNA in NS. METHODS: DNA was retrieved
      from 44 formalin-fixed, paraffin-embedded samples of NS (22 with secondary tumors
      [eg, trichoblastoma, verruca, syringocystadenoma papilliferum] and two epidermal
      nevi [EN]). Nested polymerase chain reaction with multiple degenerate consensus
      and type-specific primers and direct sequencing of polymerase chain reaction
      products was performed. For selected cases, in situ hybridization using probes
      specific for HPV 5 and 8 and for high-risk genital-mucosal HPV types was
      performed. RESULTS: HPV DNA was detected in 82% of NS and both EN, and consisted
      of genital-mucosal HPV types in 52% (HPV 6, 16, and 33) and a diverse variety of
      epidermodysplasia verruciformis-associated HPV types in 61%, including well-known
      epidermodysplasia verruciformis HPV types (5, 8, 15, 20, 22, 24, 36, 37, 38, and
      80) and putatively novel epidermodysplasia verruciformis HPV types (DL285, DL287,
      DL436, and alb-1, -2, -3, -5, -6, -7, -8, -10, -11, -12, and -13). HPV
      coinfection was frequent, found in 48% (two HPV genotypes in 35% and 3 in 13%).
      Of NS and EN, 42% had HPV genotypes associated with cancer (ie, HPV 5, 8, 16, 20,
      33, and 38); the two most commonly identified HPV types where HPV 16 (39%) and
      HPV 38 (18%). No differences were detected comparing frequency of HPV DNA
      detected with respect to age or presence of a secondary tumor. Histologically,
      all NS and EN showed HPV-associated cytopathic effects (ie, perinuclear halos,
      altered keratohyaline granules). By in situ hybridization, 64% (18/28) were
      positive, showing a low-intensity, punctate nuclear signal in epidermal and
      adnexal keratinocytes, indicating viral integration and low viral genome copy
      number. LIMITATIONS: Absence of adjacent, uninvolved normal-appearing skin
      control samples. CONCLUSION: HPV DNA is prevalent in NS, and HPV 16, the most
      frequently detected genotype, appears to be integrated into the host genome.
      Whether HPV represents a commensal infection caused by localized cutaneous
      predisposition, or is an essential factor in the pathogenesis of NS is unknown.
      The high frequency of oncogenic HPV types implicates maternal transmission of HPV
      and infection of an ectodermal stem cell leading to an epigenetic mosaic and
      altered skin development manifested along Blaschko's lines.

PMID- 18638630
TI  - Hyperhidrosis and botulinum toxin: expanding horizons.
AB  - Dialogues in Dermatology, a monthly audio program from the American Academy of
      Dermatology, contains discussions between dermatologists on timely topics.
      Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided
      after each discussion as a topic summary and are provided here as a special
      service to readers of the Journal of the American Academy of Dermatology.

PMID- 18638631
TI  - Desonide foam 0.05%: safety in children as young as 3 months.
AB  - BACKGROUND: Desonide 0.05% was recently developed in an emulsion foam
      formulation. OBJECTIVE: The safety of desonide foam 0.05% in children aged 3
      months to 17 years was evaluated in two phase II studies and one phase III study.
      METHODS: A phase II open-label study of the effect of desonide foam 0.05% on the
      hypothalamic-pituitary-adrenal axis was evaluated in pediatric and adolescent
      participants with mild-to-moderate atopic dermatitis. The phase II and III
      clinical efficacy studies evaluated adverse events. RESULTS: At the end of the 4
      week treatment in the phase II study, 4% (3 of 75) of participants experienced
      mild, reversible hypothalamic-pituitary-adrenal-axis suppression. The combined
      safety data from the phase II and III studies revealed 6% of participants in the
      desonide foam group and 14% in the vehicle foam group reported adverse events (P
      = .0002), with application site burning as the most commonly reported adverse
      event (3% in the desonide foam group vs 7% in the vehicle foam group; P = .004).
      LIMITATIONS: The studies evaluated short-term use only. CONCLUSION: Desonide foam
      was safe and well tolerated in participants as young as 3 months.

PMID- 18638632
TI  - Film photography's limitations in imaging skin of color underlies racial imaging
      disparities; new digital photography features facilitate the imaging of skin of
      color.

PMID- 18638633
TI  - Allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis.

PMID- 18638634
TI  - "Lymphocytic vasculitis" is not urticarial vasculitis.

PMID- 18638635
TI  - Evaluation of rashes in oncology patients.

PMID- 18638636
TI  - The role of patch testing in contact urticaria.

PMID- 18638637
TI  - Microfoam treatment of Klippel-Trenaunay syndrome and vascular malformations.

PMID- 18638638
TI  - Gadolinium is not deposited in the skin of patients with normal renal function
      after exposure to gadolinium-based contrast agents.

PMID- 18638639
TI  - Recent research in personality disorders. Preface.

PMID- 18638640
TI  - A dimensional model of personality disorder: proposal for DSM-V.
AB  - A proposal made for DSM-IV was to include a means with which to provide a
      dimensional profile of a patient in terms of the diagnostic categories. However,
      a suggestion of the DSM-V Research Planning Conference on personality disorders
      was to develop a more fundamental revision through an integration of alternative
      dimensional models of personality disorder and general personality structure. A
      purpose of the current article is to provide this proposal. Also discussed is a
      primary concern with respect to the implementation of any such dimensional model:
      clinical utility. Discussed in particular are concerns regarding feasibility and
      treatment implications.

PMID- 18638641
TI  - The perils of dimensionalization: challenges in distinguishing negative traits
      from personality disorders.
AB  - The harmful dysfunction analysis of mental disorder is used to assess whether
      traits are indicative of personality disorder, and the ways such an inference can
      go wrong. Personality is an overall organization that allows the organism to
      accomplish basic goals within the constraints of its basic traits and specific
      intentional states. Extreme traits can be negative or "dysfunctional" in the
      sense that they interfere with the achievement of socially or personally valued
      goals; however, they are not necessarily dysfunctions or disorders in the
      biological or medical sense. Thus, no sheer assessment of a set of traits can
      offer sufficient information for a diagnosis of personality disorder. Nor do
      criteria such as maladaptiveness, impairment, or clinical significance
      necessarily transform a trait into a personality disorder. The DSM's most
      plausible suggestion for judging when traits are dysfunctions, inflexibility, is
      also problematic because many nondisordered traits are inflexible as well.

PMID- 18638642
TI  - Epidemiology of personality disorders.
AB  - The prevalence of personality disorders (PDs) in the nonclinical community
      population was largely unknown through the early 1990s. Over the past 10 years
      the epidemiology of PD in the community has been resolved through the study of
      large, nonclinical populations that have used validated structured psychiatric
      interviews designed specifically for PDs. The median prevalence for "any PD" is
      10.6%, which is reasonably consistent across six major studies spanning three
      nations. Because 1 in 10 people suffers from a diagnosable PD and the disorders
      are associated with high levels of service use, it follows that personality
      pathology represents a major public health concern, a major research target for
      psychopathologists, and a consuming focus for clinicians.

PMID- 18638643
TI  - The frequency of personality disorders in psychiatric patients.
AB  - Community-based epidemiological studies of psychiatric disorders provide
      important information about the public health burden of these problems; however,
      because seeking treatment is related to a number of clinical and demographic
      factors, studies of the frequency and correlates of psychiatric disorders in the
      general population should be replicated in clinical populations to provide the
      practicing clinician with information that might have more direct clinical
      utility. Diagnosing co-occuring personality disorders in psychiatric patients
      with an Axis I disorder is clinically important because of their association with
      the duration, recurrence, and outcome of Axis I disorders. This article reviews
      clinical epidemiological studies of personality disorders and finds that in
      studies using semi-structured diagnostic interviews, approximately half of the
      patients interviewed have a personality disorder. Thus, as a group, personality
      disorders are among the most frequent disorders treated by psychiatrists.

PMID- 18638644
TI  - Genetics of personality disorders.
AB  - This review of the literature on genetic contributions to the etiology of
      personality disorders broadly follows the DSM classification, and begins by
      evaluating the current evidence for genetic influences on the DSM axis II
      disorders. One of the most exciting directions in psychiatric genetics is the
      rapidly developing field of molecular genetic studies aiming to identify specific
      genes correlated with psychiatric phenotypes. Personality disorders, like most
      other psychiatric diagnostic categories, are etiologically complex, which implies
      that they are influenced by several genes and several environmental factors. The
      interplay between genes and the environment is a field that is receiving
      increasing attention and is addressed both in relation to quantitative and
      molecular methods.

PMID- 18638645
TI  - Recent advances in the biological study of personality disorders.
AB  - While it is premature to provide a simple model for the vulnerability to the
      development of either borderline (BPD) or schizotypal (SPD) personality disorder,
      it is clear that these heritable disorders lend themselves to fruitful
      neurobiological exploration. The most promising findings in BPD suggest that a
      diminished top-down control of affective responses, which is likely to relate to
      deceased responsiveness of specific midline regions of prefrontal cortex, may
      underlie the affective hyperresponsiveness in this disorder. In addition, genetic
      and neuroendocrine and molecular neuroimaging findings point to a role for
      serotonin in this affective disinhibition. Clearly SPD falls within the
      schizophrenia spectrum, but precisely the nature of what predicts full-blown
      schizophrenia as opposed to the milder symptoms of SPD is not yet clear.

PMID- 18638646
TI  - The neurobiology of psychopathy.
AB  - Numerous studies have tackled the complex challenge of understanding the neural
      substrates of psychopathy, revealing that brain abnormalities exist on several
      levels and in several structures. As we discover more about complex neural
      networks, it becomes increasingly difficult to clarify how these systems interact
      with each other to produce the distinct pattern of behavioral and personality
      characteristics observed in psychopathy. The authors review the recent research
      on the neurobiology of psychopathy, beginning with molecular neuroscience work
      and progressing to the level of brain structures and their connectivity.
      Potential factors that may affect the development of brain impairments, as well
      as how some systems may be targeted for potential treatment, are discussed.

PMID- 18638647
TI  - Child development and personality disorder.
AB  - The evidence is surprisingly strong that even early adolescent personality
      disorders or elevated personality disorder symptoms have a broad range of
      negative effects well into adulthood, for the most part comparable to or even
      larger than those of Axis I disorders. Current evidence suggests that the most
      severe long-term prognosis is associated with borderline and schizotypal PDs and
      elevated symptoms. And of course, childhood conduct disorder is in a peculiar
      status, disappearing in adulthood to be manifest as a very severe disorder
      antisocial PD-in a minority of those with the adolescent disorder.

PMID- 18638648
TI  - Longitudinal course and outcome of personality disorders.
AB  - The notion of personality disorders (PDs) as stable disorders has persisted
      despite traditional follow-up studies showing that fewer than 50% of patients
      diagnosed with PDs retained these diagnoses over time. Because these studies had
      methodological limitations, four more rigorous large-scale studies of the
      naturalistic course of PDs have been conducted. The results indicate (1)
      personality psychopathology improves over time at unexpectedly significant rates;
      (2) maladaptive personality traits are more stable than PD diagnoses; (3)
      although personality psychopathology improves, residual effects can be seen in
      the form of persistent functional impairment, continuing behavioral problems,
      reduced future quality of life, and ongoing Axis I psychopathology; (4)
      improvement in personality psychopathology may eventually be associated with
      reduction in ongoing personal and social burden.

PMID- 18638649
TI  - Reasons for change in borderline personality disorder (and other axis II
      disorders).
AB  - Borderline personality disorder is a slow-moving disorder. Most patients who have
      borderline personality disorder improve over time; however, the reasons for this
      change are unclear. Therapy as usual and the reparations that adult life offers
      can facilitate these changes.

PMID- 18638650
TI  - Clinical trials of treatment for personality disorders.
AB  - The objective of this review is to examine clinical trials of the treatment of
      personality disorders (PDs). The method is a narrative review of published
      controlled trials of psychotherapy and pharmacotherapy. Results show that a
      variety of methods reduce impulsivity, with less striking results for affective
      instability. There is good support for well-structured methods of psychotherapy,
      mainly in borderline personality disorder (BPD), but evidence for the efficacy of
      pharmacotherapy is weak. Research on other PD categories is sparse.

PMID- 18638651
TI  - Assessment and emergency management of suicidality in personality disorders.
AB  - This article examines the association between suicidal behavior and personality
      disorders. It updates the review of epidemiological evidence for the association
      between suicidal behavior and suicide in individuals who have a personality
      disorder diagnosis, particularly in borderline personality disorder (BPD). The
      second part of the article presents new empirical evidence that characterizes
      suicidal behavior in patients who have BPD, specifically examining patient
      characteristics that differentiate patients who have BPD with a history of high
      versus low lethality suicide attempts. Finally, the article discusses the
      approach to a patient who has BPD and presents to the emergency department
      because of an increased risk of suicide.

PMID- 18638652
TI  - Research trends and directions in the study of personality disorder.
AB  - An examination of current research trends needs to consider both the
      prerequisites for research and the specific research directions needed to arrive
      at a more systematic understanding of the etiology, development, course, and
      treatment of personality disorder. Important prerequisites are improved
      phenotypes and more sophisticated research designs to explicate mechanisms
      specific to the various patterns of personality disorder. Specific research
      themes with promise are systematic studies of gene-environment interplay,
      investigations of biological substrates, and longitudinal studies capable of
      generating information on how the different domains of personality pathology
      change over time. There also needs to be a new generation of treatment research
      that is less concerned with comparing the outcome of treatments that often seem
      modest in effects and limited in scope and more concerned with identifying the
      most effective treatment methods for each domain of psychopathology. Along with
      these developments it is also important that research pays more attention to how
      the integrative processes within personality become dysfunctional in personality
      disorder.

PMID- 18638653
TI  - De novo autoimmunity after organ transplantation: targets and possible pathways.
AB  - The development of autoantibodies to different tissue-specific antigens in
      patients without existing history of autoimmune diseases suggests that
      autoimmunity may develop de novo after organ transplantation. In addition to allo
      specific immune responses, tissue-specific autoimmunity also appears contribute
      to the host anti-graft response, and thus may affect long-term graft function. As
      graft failure caused by chronic rejection is a major challenge in clinical
      transplantation, understanding de novo autoreactivity after transplantation has
      important ramifications. This review investigates this emerging concept by
      discussing target antigens and possible pathways.

PMID- 18638654
TI  - Regulatory T cells after organ transplantation: where does their action take
      place?
AB  - Regulatory T cells are considered to be pivotal for the induction of tolerance to
      donor antigens. In the past decades, several regulatory T-cell subsets have been
      identified, such as CD4(+)CD25(+) regulatory T cells and the CD8(+)CD28(-)
      suppressor T cells. Although many studies have investigated the role of these
      regulators in transplant tolerance, relatively little attention has focused on
      the exact place where these cells suppress immune responses directed to donor
      antigens. The localization of regulatory T cells may influence their effect on
      allogeneic immune responses. More insight into the localization and migration of
      regulatory T cells in transplant recipients is therefore important, especially
      when these cells are to be used for monitoring purposes and for cellular immune
      therapy. In the present review we summarize current knowledge about the presence
      of functional donor-directed regulatory T cells in the secondary lymphoid organs,
      peripheral blood, and the transplanted organ itself. In addition, we discuss the
      importance of the appropriate localization for the control of anti-donor immune
      reactivity.

PMID- 18638655
TI  - Critical role of activation-inducible lymphocyte immunomediatory
      molecule/inducible costimulator in the effector function of human T cells: a
      comparative in vitro study of effects of its blockade and CD28 blockade in human
      beings and monkeys.
AB  - Activation-inducible lymphocyte immunomediatory molecule (AILIM; also referred to
      as inducible costimulator, ICOS) is the third homolog of the "professional"
      costimulatory molecule, CD28. To date, the characteristics and role of
      AILIM/ICOS, especially in effector function of T cells, have been determined
      through numerous studies in vitro and in vivo using mice. Considering potential
      differences among species, whether the AILIM/ICOS blockade acts as an efficacious
      immunomodulator for human diseases remains to be elucidated. In the present
      study, ability of AILIM/ICOS blockade to modulate immune responses of human and
      monkey cells was investigated using a fully human antibody (JTA-009), comparing
      the effect of CD28 blockade. JTA-009 blocked the response of human and monkey T
      cells co-stimulated with anti-CD3 and AILIM/ICOS ligand, B7h. AILIM/ICOS and CD28
      blockade both inhibited human mixed lymphocyte reaction in different fashions, as
      well as cytokine production in T helper (Th) 1-/Th2-type recall responses. In
      monkeys however, CD28 blockade by CTLA4-Ig effectively prevented mixed lymphocyte
      reaction to a greater extent than AILIM/ICOS blockade. These results suggest that
      AILIM/ICOS blockade is valuable for suppressing both primary allogenic response
      and recall responses of T cell in human beings, and that there are differences
      between human and monkey use preferences for costimulatory molecules.

PMID- 18638656
TI  - Pre- and postoperative levels in serum of mannan-binding lectin associated serine
      protease-2 -a prognostic marker in colorectal cancer.
AB  - Mannan-binding lectin-associated serine protease-2 (MASP-2) is the initiating
      enzyme of the lectin pathway of complement activation. High preoperative serum
      levels of MASP-2 are associated with recurrence and poor survival in patients
      with colorectal cancer (CRC). In this study we investigate the prognostic role of
      MASP-2 in patients curatively resected for primary CRC. Serum concentrations of
      MASP-2 were determined in 281 patients prior to surgery and 7 months
      postoperatively using a time-resolved immunofluorometric assay. End points were
      recurrent cancer and death within a median follow-up time of 7.9 years. The
      correlation between pre- and postoperative levels was 0.49. High postoperative
      levels of MASP-2 were significantly associated with poor survival [p = 0.04;
      hazard ratio (HR) = 1.35; 95% confidence interval (CI), 1.02-1.80] and recurrence
      (p = 0.01, HR = 1.6, 95% CI, 1.1-1.6). The inclusion of age, gender, tumor
      localization, and Dukes stage in multivariate analysis demonstrated that high
      MASP-2 levels were independently predictive of survival (p = 0.01; HR = 1.5, 95%
      CI, 1.1-2.0) and recurrence (p = 0.01, HR = 1.6; 95% CI, 1.1-2.4). Combining pre-
      and postoperative MASP-2 levels did not improve the prediction of
      survival/recurrence. High postoperative levels of MASP-2 are associated with poor
      prognosis in patients curatively resected for CRC. A change of the MASP-2 level
      from preoperative levels was not, per se, predictive of recurrent disease or
      survival.

PMID- 18638657
TI  - Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible
      factor 1alpha in activated human T lymphocytes.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is critical not only in the
      regulation of oxygen homeostasis but also in the regulation of innate and
      adaptive immune systems. We previously reported that T-cell receptor-mediated
      activation of T cells in mice leads to the expression of an alternative isoform
      of HIF-1alpha that inhibits activated T cells in a delayed negative feed-back
      manner. In this paper, we describe a novel mRNA isoform of human HIF-1alpha that
      is upregulated in peripheral T lymphocytes after T-cell receptor stimulation.
      This activation- inducible isoform is expressed using the alternative first exon
      I.3, and it encodes a protein that is 24 amino acids longer than the ubiquitous
      HIF-1alpha isoform. This mRNA isoform I.3 of HIF-1alpha is expressed in a tissue
      specific manner with the highest expression found in peripheral blood leukocytes
      and the thymus.

PMID- 18638658
TI  - Activating KIR genes are associated with ankylosing spondylitis in Asian
      populations.
AB  - Killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen
      (HLA) loci are both highly polymorphic. The aim of this study was to perform a
      KIR genotype analysis and examine, in concert with HLA-B27 genotypes, their
      influence on ankylosing spondylitis (AS) susceptibility in two Asian populations
      (one from China, 42 patients and 30 controls, and another from Thailand, 30
      patients and 16 controls). In the Chinese population, we observed an increase of
      KIR3DS1, KIR2DS5, and KIR2DL5 gene frequencies in AS patients (p(c) < 0.005, p(c)
      < 0.001, and p(c) < 0.01, respectively). A similar increase was reported in the
      Thai population: KIR3DS1, KIR2DS5, and KIR2DL5 gene frequencies were higher in AS
      (p(c) < 0.05, p < 0.05, and p(c) < 0.05, respectively). Upon analyzing the
      KIR3DL1/3DS1 genotypes, we determined significant differences in both
      populations. The frequency of 3DL1/3DL1 was decreased in AS (p(c) < 0.005 and
      p(c) < 0.05 in the Chinese and Thai populations, respectively), whereas 3DL1/3DS1
      demonstrated an increased frequency in AS (p(c) < 0.005 in the Chinese population
      and p(c) < 0.05 in the Thai population).

PMID- 18638660
TI  - Low-dietary protein intake induces problems with glucose homeostasis and results
      in hepatic steatosis in heavy milk-fed calves.
AB  - We studied effects of protein intake at two protein-free energy intake levels on
      plasma glucose and insulin concentrations, urinary glucose excretion and on liver
      and intestinal fat content in milk-fed veal calves. Two experiments were
      performed at body weights (BW) of 80-160 kg (mean 120 kg; Exp. 1) and 160-240 kg
      (mean 200 kg; Exp. 2). In each experiment, 36 calves were allocated to one of six
      protein intake levels, at each of two energy intake levels. Digestible protein
      intakes ranged between 0.90 and 2.72 g nitrogen (N)/(kg BW(0.75) x d) in Exp. 1
      and between 0.54 and 2.22 g N/(kg BW(0.75)x d) in Exp. 2. The two energy intake
      levels were kept constant on a protein-free basis and were 663 and 851 kJ/(kg
      BW(0.75) x d) in Exp. 1 and 564 and 752 kJ/(kg BW(0.75)x d) in Exp. 2. Blood
      samples were taken between 5 and 6h post-feeding at 14-d intervals until calves
      reached target BW, and liver fat mass was determined at slaughter. Urinary
      glucose excretion was quantified at 120 and 200 kg BW in Exps. 1 and 2,
      respectively. Increased protein-free energy intake increased plasma glucose
      concentrations and urinary glucose losses in 200 kg calves, but not in 120 kg
      calves. Increasing protein intake decreased plasma glucose, urinary glucose and
      plasma insulin in both experiments. Liver fat content decreased with increasing
      protein intake. In conclusion, long-term low-dietary protein intake increased
      hyperglycemia, hyperinsulinemia, glucosuria and hepatic steatosis in heavy milk
      fed calves, likely associated with increased insulin resistance.

PMID- 18638661
TI  - Uncoupling protein expression in skeletal muscle and adipose tissue in response
      to in vivo porcine somatotropin treatment.
AB  - These experiments examined the potential roles of somatropin (pST) and IGF-I in
      the regulation of uncoupling protein (UCP)2 and UCP3 and their regulatory
      proteins peroxisome proliferator activated receptor (PPAR) alpha, gamma and delta
      using in vivo pST treatment of swine and in vitro supplementation of pST or IGF-I
      to adipose slices. Six, 90kg barrows were treated with recombinant pST (10mg) for
      2 week while another six pigs were injected with buffer. Total RNA from outer
      subcutaneous adipose (OSQ) and middle subcutaneous adipose (MSQ) tissues, leaf
      fat, liver and longissimus (LM) was amplified by reverse transcription-PCR with
      quantification of transcripts by capillary electrophoresis with laser-induced
      fluorescence detection. UCP2 mRNA abundance increased in liver (P<0.001) and all
      three adipose tissues by pST treatment (P<0.05). Administration of pST increased
      UCP3 mRNA abundance by 42% in LM (P<0.01). PPARalpha mRNA abundance increased
      with pST treatment by 29% in liver (P<0.05), while decreasing 25% in LM (P<0.05).
      PPARgamma mRNA abundance decreased 32% (P<0.01) while PPARdelta increased 48% in
      LM (P<0.01) with pST administration. In vitro, pST reduced UCP2 mRNA abundance in
      OSQ and MSQ tissue slices (P<0.05). UCP3 mRNA abundance decreased in OSQ (P<0.05)
      but increased in MSQ (P<0.05) with pST. In contrast, IGF-I increased UCP2 and
      UCP3 mRNA abundance in both MSQ and OSQ slices (P<0.05). These experiments
      suggest pST, IGF-I and metabolic adaptations to pST contribute to regulating UCP2
      and UCP3.

PMID- 18638662
TI  - Role for des-acyl ghrelin in the responsiveness of plasma hormones and
      metabolites to ghrelin in Holstein steers.
AB  - Gastric-derived peptide hormone ghrelin is known for its potent growth hormone
      (GH) stimulatory effects. The acyl-modification on N-terminal Ser(3) residue is
      reported to be important to stimulate the ghrelin receptor, GH secretagogue
      receptor type1a (GHS-R1a). However, major portion of circulating ghrelin lacks in
      acylation, and some biological properties of des-acyl ghrelin have been reported
      in monogastric animals. In the present study, the responsiveness of plasma
      hormones and metabolites to ghrelin in steers was characterized, and role for des
      acyl ghrelin in these changes was investigated. The repeated intravenous
      administrations of bovine ghrelin (1.0 microg/kg BW) every 2h for 8h to Holstein
      steers significantly increased the plasma acylated ghrelin, total ghrelin, GH,
      insulin and NEFA levels. The GH responses in peak values and area under the
      curves (AUCs) were attenuated by repeated injections of ghrelin, however, the
      responses of plasma total ghrelin were similar. Plasma insulin AUC decreased
      after fourth injection of ghrelin while plasma NEFA AUCs gradually increased by
      repeated injections of ghrelin. Pretreatment of des-acyl ghrelin (10.0 microg/kg
      BW) 5 min prior to the single injection of ghrelin (1.0 microg/kg BW) did not
      affect the ghrelin-induced hormonal changes. Moreover, the responses of plasma GH
      to bovine and porcine ghrelin, which differ in C-terminal amino acid residues,
      were similar in calves. These data show that (1) GH release was attenuated by
      repeated administration of ghrelin, (2) ghrelin regulates glucose and fatty acid
      metabolism probably via different pathway, and (3) des-acyl ghrelin is unlikely
      the antagonist for ghrelin to induce endocrine effects in Holstein steers.

PMID- 18638659
TI  - Balancing selection and heterogeneity across the classical human leukocyte
      antigen loci: a meta-analytic review of 497 population studies.
AB  - This paper presents a meta-analysis of high-resolution human leukocyte antigen
      (HLA) allele frequency data describing 497 population samples. Most of the
      datasets were compiled from studies published in eight journals from 1990 to
      2007; additional datasets came from the International Histocompatibility
      Workshops and from the AlleleFrequencies.net database. In all, these data
      represent approximately 66,800 individuals from throughout the world, providing
      an opportunity to observe trends that may not have been evident at the time the
      data were originally analyzed, especially with regard to the relative importance
      of balancing selection among the HLA loci. Population genetic measures of allele
      frequency distributions were summarized across populations by locus and
      geographic region. A role for balancing selection maintaining much of HLA
      variation was confirmed. Further, the breadth of this meta-analysis allowed the
      ranking of the HLA loci, with DQA1 and HLA-C showing the strongest balancing
      selection and DPB1 being compatible with neutrality. Comparisons of the allelic
      spectra reported by studies since 1990 indicate that most of the HLA alleles
      identified since 2000 are very-low-frequency alleles. The literature-based allele
      count data, as well as maps summarizing the geographic distributions for each
      allele, are available online.

PMID- 18638663
TI  - Adiponectin enhances in vitro development of swine embryos.
AB  - Recent studies have shown that factors from adipose tissue influence and regulate
      the reproductive system. Hormones such as leptin and resistin are now known to
      regulate several reproductive processes. Adiponectin is the most abundant protein
      secreted by adipose tissue, and its circulating concentration is inversely
      related to adiposity and body mass index. Little is known about the involvement
      of adiponectin in reproduction. In the present study, the effect of recombinant
      adiponectin on the meiotic maturation and early embryo development in vitro was
      investigated, using porcine oocytes. Adiponectin receptors, AdipoR1 and AdipoR2,
      were found to be expressed in porcine oocytes and cumulus cells of both small and
      large follicles. Both AdipoR1 and AdipoR2 were immunolocalized to cumulus-oocyte
      complexes (COCs), oocytes, and early developing embryos. When included in oocyte
      maturation medium for 46 h, adiponectin significantly decreased the frequency of
      meiotic immature oocytes derived from large follicles (3-6 mm) but not from small
      follicles (<3mm). From studies of oocytes matured in the presence of adiponectin
      and mitogen-activated protein kinase (MAPK) pathway inhibitors MEK1 (PD98059),
      MEK1/2 (U0126), and p38MAPK (SB203580) it was concluded that adiponectin enhances
      oocyte maturation thought the p38MAPK pathway. Finally, a superior rate of embryo
      development to the blastocyst stage was achieved by embryos cultured in the
      presence of adiponectin. These results indicate that adiponectin has a positive
      effect on the meiotic maturation and in vitro embryo development of porcine
      oocytes and suggests a physiological role for this adipokine in early development
      in mammals.

PMID- 18638664
TI  - The pig p160 co-activator family: full length cDNA cloning, expression and
      effects on intramuscular fat content in Longissimus Dorsi muscle.
AB  - Evidence has shown in mouse that the p160 co-activator family, consisting of
      nuclear receptor co-activators 1 (NCOA1), 2 (NCOA2) and 3 (NCOA3) plays a
      critical role in adipogenesis. In the present study, we cloned these three
      porcine genes, identified their transcript variants and analyzed their expression
      level in relation to intramuscular fat (IMF) content in Longissimus Dorsi (LD)
      muscle. Both in silico cloning and PCR amplification revealed a full length cDNA
      sequence of 6591bp for NCOA1 (EU346671), 7628bp for NCOA2 (EU346672) and 5005bp
      for NCOA3 (EU346674) in pigs, respectively. Interestingly, three transcript
      variants were identified for the porcine NCOA1 and two for the porcine NCOA2
      gene. In addition, the deduced amino acid sequences indicated that isoform 2 of
      NCOA2 lacks the fourth LXXLL motif, the number of which has been shown to
      influence the selectivity and affinity for different nuclear receptors. Finally,
      15 animals with high IMF content and fifteen animals with low IMF content
      (p<0.05) selected from 60 individuals were used to investigate how the family
      members and their variants affect the phenotype in pigs using real-time PCR. Our
      results showed that both NCOA1 transcript variant 2 (r=-0.554, p<0.01) and total
      NCOA1 (r=-0.516, p<0.01) expression levels were negatively correlated with IMF
      contents, while NCOA2 transcript variant 1 (r=0.605, p<0.01) and NCOA3 (r=0.435,
      p<0.05) were positively associated with IMF content in LD muscle. Overall, the
      present study provides evidence for the first time that the p160 co-activator
      family might have a concordant effect on lipid metabolism in mammals.

PMID- 18638665
TI  - Leukemia inhibitory factor protein and receptors are expressed in the bovine
      adrenal cortex and increase cortisol and decrease adrenal androgen release.
AB  - The release of adrenal steroids during acute stress is primarily regulated by
      adrenocorticotropic hormone (ACTH). In contrast, during chronic inflammatory
      stress additional factors are involved in regulating adrenal function. Leukemia
      inhibitory factor (LIF) is a pleiotropic cytokine that increases ACTH release
      from the pituitary. In addition, LIF and LIF receptors (LIFR) are expressed in
      the human adrenal cortex and the human adrenocortical tumor cell line H295R.
      Furthermore, LIF increases basal and ACTH-stimulated cortisol release from H295R
      cells. However, the expression of LIF and LIFR in non-human adrenal glands and
      the effects of LIF on the release of cortisol from adrenal cells of non-human
      species have not been determined. Furthermore, the effects of LIF on adrenal
      androgen release from all species are unknown. In this study,
      immunohistochemistry, Western blots, RT-PCR, and nucleotide sequencing was
      utilized to demonstrate that LIF and its receptor are expressed throughout the
      bovine adrenal cortex. Although LIF did not modify basal cortisol release from
      dispersed cells isolated from the bovine adrenal zona fasciculate, this cytokine
      increased ACTH-stimulated release of cortisol from these cells in a manner
      dependent on the LIF concentration and exposure interval. In contrast, LIF in a
      concentration-dependent and time-dependent manner decreased basal and ACTH
      stimulated adrenal androgen release from dispersed cells isolated from the bovine
      adrenal zona reticularis. Because LIF release increases during inflammatory
      stress and this cytokine stimulates adrenal cortisol release and inhibits adrenal
      androgen release, this cytokine may play an important role in regulating the
      release of adrenal steroids during inflammatory stress.

PMID- 18638666
TI  - Localization of CCK-1R in the omasum and role of CCK in the regulation of omasal
      contractions in sheep.
AB  - The present study examined localization of cholecystokinin receptor (CCK-R) mRNA
      in the muscle layer of the ovine omasum and role of CCK-R type 1 (CCK-1R) in the
      regulation of muscle contraction of the omasum. We demonstrated that not only CCK
      R type 2 (CCK-2R) mRNA but also CCK-1R mRNA is highly expressed in the muscle
      layer of the ovine omasum. Application of CCK-8 to muscle strips of the greater
      curvature of the ovine omasum at 1-100 nM induced tonic contraction in a
      concentration-dependent manner, and the contractile effect of CCK-8 was inhibited
      by both CCK-1R antagonist lorglumide (IC(50) 2.7 and 7.9 microM in the
      longitudinal and circular muscle, respectively) and CCK-2R antagonist PD135,158
      (IC(50) 51.4 microM in the longitudinal muscle), indicating that not only CCK-2R
      but also CCK-1R is functionally expressed in the plasma membrane of smooth
      muscles in the omasum and mediates action of exogenous CCK. Contractile effect of
      intravenous infusion of CCK-8 (1-30 pmol/kg/min) on omasal contraction was also
      confirmed in the in vivo experiments using conscious sheep in the absence and
      presence of atropine infusion (14.4 nmol/kg/min), and showed that circulating CCK
      increases omasal electromyographic (EMG) activity at lower plasma concentration
      than that it inhibits ruminal contractions. Taking account of our previous
      results in the in vivo study using other CCK-1R antagonist, it is suggested that
      circulating CCK, even at normal range of plasma concentration, plays a
      physiological role as a regulator of omasal contractions in sheep and CCK-1R
      mediates the action of CCK.

PMID- 18638667
TI  - Forthcoming issues to confront as children and youth with special health care
      needs grow up.

PMID- 18638668
TI  - Qualitative study on the role of nurses as health case managers of children in
      foster care in California.
AB  - This qualitative study on nurses who provide health case management for children
      in foster care examined their vision for the care needed to improve health
      outcomes. A purposive sample of eight public health nurses was selected to
      participate in semistructured interviews. Data were analyzed using content
      analysis to formulate a narrative description of the nurses' vision. Two themes
      emerged from the data: (1) the desire to give holistic care with an emphasis on
      mental health care and (2) the difficulty with providing preventive care as a
      result of multiple causes of health problems.

PMID- 18638669
TI  - Fathers' perspectives on the emotional impact of managing the care of their
      children with cystic fibrosis.
AB  - In this article, fathers' perspectives on the emotional impact of managing the
      care of their children with cystic fibrosis (CF) are examined. The constant worry
      of living with the unpredictability of CF was highlighted in this study, drawing
      on interviews with eight Irish fathers, who experienced difficulties
      communicating their concerns to others. Despite efforts at not dwelling on CF,
      fathers described being surrounded by constant reminders. To minimize the
      emotional impact of managing their children's care, fathers described living from
      day to day rather than looking into the future. These findings demonstrate the
      need for supportive interventions in helping fathers manage the emotional demands
      of caring for their children with CF.

PMID- 18638670
TI  - A journey to pediatric chemotherapy competence.
AB  - Chemotherapy and biotherapy use has increased due to its effectiveness as a
      treatment for childhood cancer. Nurses need to demonstrate knowledge of these
      agents' mechanism of action, adverse effects, safe handling, and monitoring
      parameters. Competence of nurses administering chemotherapy and biotherapy needs
      to be assessed to ensure safety and quality care. Review of literature reveals
      that a comprehensive education program and skills validation are the most
      thorough means of assessing chemotherapy competency. The chemotherapy competency
      program at the Children's National Medical Center (CNMC) was evaluated and was
      noted to be inadequate. Although a self-learning module on intravenous push
      chemotherapy administration and a 1-hour lecture on chemotherapy administration
      were offered during orientation, there was limited reevaluation of competence at
      regular intervals. As a result of a literature review, multi-institutional
      surveys, and intensive review of the CNMC chemotherapy administration module, a
      comprehensive chemotherapy/biotherapy competency program was developed for nurses
      administering chemotherapeutic agents. The CNMC chemotherapy competency program
      was formed with a didactic content course utilizing the Oncology Nursing Society
      Chemotherapy/Biotherapy Provider Course combined with initial and yearly skills
      validation. After offering both the didactic portion and three-part competency
      skills set, nurses have indicated improved satisfaction with the methodology of
      achieving chemotherapy competency.

PMID- 18638671
TI  - Mentoring beyond the first year: predictors of mentoring benefits for pediatric
      staff nurse proteges.
AB  - This research study explored mentoring benefits among pediatric staff nurse
      proteges through application of a business mentoring model, the Mutual Benefits
      Model (Zey, 1991), to nursing. The main finding of this study was that mentoring
      quality was the single best predictor of mentoring benefits among pediatric staff
      nurse proteges. The major implication of this study is that nursing leaders and
      organizations can make lasting impacts through high-quality mentoring
      relationships even when they are time and resource limited. This study and its
      pilot study provided a valid and reliable nursing research instrument, the
      Jakubik Mentoring Benefits Questionnaire, for use in future research to further
      explore the benefits of mentoring among pediatric nurses. The findings of this
      study support the conceptualization of effective mentoring relationships in
      nursing as a triad among the individual mentor, the protege, and the organization
      where they work rather than a dyad relationship between the mentor and protege
      only.

PMID- 18638672
TI  - Readiness for discharge in parents of hospitalized children.
AB  - Parental preparation for a child's discharge from the hospital sets the stage for
      successful transitioning to care and recovery at home. In this study of 135
      parents of hospitalized children, the quality of discharge teaching, particularly
      the nurses' skills in "delivery" of parent teaching, was associated with
      increased parental readiness for discharge, which was associated with less coping
      difficulty during the first 3 weeks postdischarge. Parental coping difficulty was
      predictive of greater utilization of posthospitalization health services. These
      results validate the role of the skilled nurse as a teacher in promoting positive
      outcomes at discharge and beyond the hospitalization.

PMID- 18638673
TI  - Developmental diversity in symptom research involving children and adolescents
      with cancer.
AB  - The purpose of this literature review was to evaluate developmental diversity in
      studies describing physical symptoms in children and adolescents receiving cancer
      treatment. Developmental diversity was conceptualized as individual differences
      based on normal stages of human development, including cognitive, psychosocial,
      and physiologic aspects. Searches of Medline and the Cumulative Index of Nursing
      and Allied Health Literature identified 53 articles published between January
      1986 and November 2006. Most studies addressed symptoms in school-aged children
      and adolescents; few compared symptoms across age groups. Additional measures are
      needed to describe younger children's symptoms. Alternate research methodologies
      may be appropriate to describe their symptom experiences.

PMID- 18638674
TI  - Narratives of children with chronic illness about being comforted.
AB  - The aim of the study was to examine how children with chronic illnesses narrate
      their experience of being comforted in hospital. During interviews, seven
      children, 4-10 years old described their experiences and made drawings. Thematic
      content analysis revealed following themes: being physically close to one's
      family, feeling safe and secure, staff being there for the children, and children
      being there for parents and siblings. Mother was identified as the most important
      comforter. The findings suggest that trusting in the staff's knowledge and
      professional skills is a prerequisite for children to feel "at home", and safe in
      hospital. Being close to one's family is even more important.

PMID- 18638675
TI  - Sound spectral analysis in the intensive care nursery: measuring high-frequency
      sound.
AB  - Uterine structures protect the fetus from high-frequency sounds (i.e., >500 Hz).
      Preterm infants are not protected from sound >500 Hz. It is necessary to assess
      sound frequencies to protect preterm infants from high-frequency sound. However,
      no noise measurement study has been reported using sound spectral analysis (SSA).
      This article reports the results of an SSA in two Level III neonatal intensive
      care units (NICUs). The results of the SSA indicated that significant high
      frequency sound existed within the infant's immediate care environment. Results
      of SSA assessments may lend evidentiary support to clinical managers seeking to
      redesign traditional NICUs.

PMID- 18638676
TI  - Pain mechanisms and management in the rheumatic diseases. Preface.

PMID- 18638677
TI  - New concepts in rheumatic pain.
AB  - The inclusion of pain as the fifth vital sign in clinical medicine underlines the
      importance of this symptom. Pain that is consistently present in any rheumatic
      condition should be considered a specific disease entity, which should be
      actively managed in parallel with the rheumatic complaint. Rheumatic pain is the
      most prevalent pain syndrome worldwide and will be experienced by almost all
      persons during their lifetime. Pain results in a significant burden of suffering
      that affects overall well-being as well as sleep, mood, and energy. Understanding
      of pain mechanisms from the anatomic and molecular perspectives has advanced,
      prompting the use of more varied pain interventions beyond simple analgesic
      medications.

PMID- 18638678
TI  - The physiology of pain mechanisms: from the periphery to the brain.
AB  - This article introduces the scientific basis for the understanding of pain
      mechanisms and highlights the importance of endogenous excitatory and inhibitory
      controls in the central nervous system. These innate control systems have an
      impact on the evolution of chronic pain and may be manipulated to alter the pain
      process, and therefore have implications regarding treatment. Understanding
      neurophysiologic mechanisms involved in the development and maintenance of pain
      can help the clinician to devise a more effective treatment plan guided by
      pathophysiologic dysfunction. Keeping in mind the heterogeneity of the pain
      response and the unique characteristics of an individual patient will lead to
      better patient care.

PMID- 18638679
TI  - The assessment of musculoskeletal pain in the clinical setting.
AB  - Pain is a primary symptom in musculoskeletal conditions, and aspects of the pain
      experience (eg, severity) are key considerations in clinical decision-making and
      in the outcome of trials and interventions. Consequently, appropriate assessment
      of pain is essential. This article reviews the measures most commonly used in
      rheumatology practice, arguing that many are significantly limited in their
      ability to reflect the complexity of the patient's experience. The authors
      provide examples of alternative approaches, concluding that there is real scope
      for improving assessment and measurement of musculoskeletal pain in the clinical
      setting.

PMID- 18638680
TI  - Placebo response: relevance to the rheumatic diseases.
AB  - Recent interest in the neurobiology of the placebo effect has brought about a new
      awareness of its potential exploitation for patient benefit, framing it as a
      positive context effect with the power to influence therapy outcome. Among the
      different placebo effects described in clinical conditions and experimental
      settings, placebo analgesia is of particular relevance to the rheumatologist.
      Placebo analgesia is the field that has most contributed to our understanding of
      the multiple mechanisms underlying this phenomenon. The possible clinical
      applications of placebo studies range from the design of clinical trials
      incorporating specific recommendations and minimizing the use of placebo arms to
      the optimization of the context surrounding the patient so that the placebo
      component in any treatment is maximized.

PMID- 18638682
TI  - The pharmacotherapy of chronic pain.
AB  - Most patients with rheumatic diseases experience difficulties with chronic pain.
      To assist clinicians in directly addressing this pain, this article presents a
      treatment approach and algorithm based on best evidence. The usual approach for
      mild to moderate pain is to start with a nonopioid analgesic. If this is
      inadequate or poorly tolerated, and if there is an element of sleep loss, it is
      then reasonable to add an antidepressant with analgesic qualities. If there is a
      component of neuropathic pain or fibromyalgia, then a trial of one of the
      gabapentinoids is appropriate. If these steps are inadequate, then an opioid
      analgesic may be added. For moderate to severe pain, one would initiate a trial
      of chronic opioid earlier. Cannabinoids and topicals may also be appropriate as
      single agents or in combination.

PMID- 18638683
TI  - Opioids for nonmalignant pain.
AB  - Pain is the most common symptom in the world for which patients seek professional
      help. Opioids offer an appropriate and safe treatment for some but not all
      patients with nonmalignant chronic pain. Potential risks, including drug abuse
      and intolerable side effects, appear to be manageable or even preventable in most
      cases. Patients with persistent rheumatic pain who have failed traditional
      treatments should be considered for long-acting opioids. Opioids are best
      administered in the framework of weighing the good against the bad in each
      patient, recognizing the potential morbidity and sometimes mortality in untreated
      patients who have severe and disabling pain daily.

PMID- 18638681
TI  - Psychologic interventions and lifestyle modifications for arthritis pain
      management.
AB  - This article provides an overview of self-management interventions used to manage
      pain in patients who have arthritis. The article is divided in two major
      sections. The first section reviews psychologic interventions used to manage
      arthritis pain, including pain-coping skills training and cognitive behavioral
      therapy for pain management, emotional disclosure interventions, and partner
      assisted interventions. The second section addresses lifestyle behavioral weight
      loss interventions used to reduce arthritis pain. In each section, the authors
      briefly describe the rationale and nature of the interventions, present data on
      their efficacy, and highlight potential future research directions.

PMID- 18638684
TI  - Topical agents in the treatment of rheumatic pain.
AB  - In rheumatic pain there is good evidence that topical nonsteroidal anti
      inflammatory drugs are about as effective as oral nonsteroidal anti-inflammatory
      drugs, but are probably safer and more tolerable because of much less systemic
      absorption and lower plasma concentrations. The best information is for topical
      diclofenac. For topical capsaicin, evidence of efficacy is trivial. For topical
      rubefacients there is no evidence of efficacy.

PMID- 18638685
TI  - Antidepressant use in painful rheumatic conditions.
AB  - This article reviews the pharmacologic and clinical evidence supporting the use
      of antidepressant drugs for treating painful rheumatologic conditions. Clinical
      studies have shown that tricyclic antidepressants, even at low doses, have
      analgesic effects in rheumatologic conditions equivalent to those of serotonin
      and noradrenalin reuptake inhibitors, but are less well tolerated. Selective
      serotonin reuptake inhibitors may also have analgesic effects, but higher doses
      are required to achieve analgesia in conditions such as fibromyalgia and low back
      pain. Antidepressant drugs may be useful in painful rheumatologic conditions, but
      in some studies the analgesic effects of antidepressants may be associated with
      functional impairment, sleep disorders, and fatigue. Further studies are required
      to determine antidepressants' analgesic mechanism of action and the specific role
      they should play in the management of chronic painful rheumatologic conditions.

PMID- 18638686
TI  - Complementary treatments in rheumatic diseases.
AB  - Which complementary therapies are effective for reducing pain in which rheumatic
      conditions? This is the question this article addresses, with particular emphasis
      on treatments that are, according to the totality of the available trial data,
      likely to be effective, and with a focus on six conditions relevant to
      rheumatologists: back pain, fibromyalgia, myofascial pain, neck pain,
      osteoarthritis, and rheumatoid arthritis.

PMID- 18638687
TI  - Dietary omega-3 fats for treatment of inflammatory joint disease: efficacy and
      utility.
AB  - There is high level evidence (meta-analysis of randomized, controlled trials) for
      symptomatic benefits from fish oil use in rheumatoid arthritis, and there is
      biologic plausibility for its clinical effects. Fish oil also has safety
      advantages in reducing cardiovascular risk via direct cardiovascular effects and
      via nonsteroidal anti-inflammatory drug-sparing. This is an important aspect of
      fish oil use, given the increased cardiovascular risk in rheumatoid arthritis.
      Perceived barriers to clinical use are readily addressed.

PMID- 18638688
TI  - New horizons in pharmacologic treatment for rheumatic disease pain.
AB  - Chronic pain is the major concern for patients with rheumatic diseases, such as
      low back pain, osteoarthritis, and rheumatoid arthritis, but current therapies
      are suboptimal. Animal models and emerging clinical data indicate that there is a
      complex spectrum of neurologic changes, manifesting both nociceptive and
      neuropathic pain, which are driven by joint pathophysiology and abnormal
      excitability in peripheral and central pain pathways. A variety of mechanisms and
      molecular drivers have been identified that can support future segmentation of
      musculoskeletal pain patients. Emerging therapies are directed to targeting
      inflammatory mediators, ligand and voltage regulated ion channels, as well as
      increasing inhibition through monoaminergic modulation. Finally, neurotrophic
      abnormalities may be restored through the modulation of specific neurotrophins.
      These developments are supported by increasing emphasis on the clinical
      understanding of the neurologic changes in pain patients to enable confident
      translation to clinical application.

PMID- 18638689
TI  - Complementary and alternative medicine.

PMID- 18638690
TI  - Dietary supplement use in cancer care: help or harm.
AB  - Conventional wisdom generally recommends complete avoidance of all dietary
      supplements, especially during chemotherapy and radiation. This interdiction
      persists, in spite of high rates of dietary supplement use by patients throughout
      all phases of cancer care, and can result in patients' perceptions of physicians
      as negative, thus leading to widespread nondisclosure of use. A review of the
      clinical literature shows that some evidence for harm does exist; however, data
      also exist that show benefit from using certain well-qualified supplements.
      Physicians should increase their knowledge base about dietary supplement use in
      cancer and consider all of the data when advising patients. Strategies that are
      patient-centered and reflect the complete array of available evidence lead to
      more nuanced messages about dietary supplement use in cancer. This should
      encourage greater disclosure of use by patients and ultimately increase safety
      and efficacy for patients choosing to use dietary supplements during cancer care.

PMID- 18638691
TI  - Review of reliable information sources related to integrative oncology.
AB  - Health care professionals, patients, and care givers require access to good
      quality, reliable information about integrative oncology. Despite the vast
      resources available, it can be difficult to find objective, evidence-based
      information. This article provides an overview of reliable integrative oncology
      information from various resources. Selection methods are detailed and evaluation
      performed using a validated instrument. Resources that met the selection criteria
      and produced high evaluation scores are reviewed in detail. Resources include
      research databases, clinical databases, online information systems, and print
      media.

PMID- 18638693
TI  - The value of massage therapy in cancer care.
AB  - Massage therapy is increasingly available as a supportive therapy to patients in
      medical centers providing cancer treatment. This article provides an overview of
      the evidence base relevant to the use of massage with the intended goal of
      alleviating symptoms and side effects experienced by cancer patients.
      Collectively, the available data support the view that massage, modified
      appropriately, offers potential beneficial effects for cancer patients in terms
      of reducing anxiety and pain and other symptoms. Replication of preliminary
      studies with larger, more homogeneous patient samples and rigorous study designs
      will help to clarify which massage modalities have the most potential benefit for
      which patients before, during, and after specific types of cancer treatment.

PMID- 18638694
TI  - Evidence-based botanical research: applications and challenges.
AB  - Use of herbal supplements is on the rise around the world, but limited data exist
      on the safety and efficacy of botanical products. Efforts to subject botanicals
      to rigorous scientific research began recently. There are many problems
      associated with botanicals research, however. These include procuring the study
      agents, selecting appropriate study method and clinical trial design, navigating
      through regulatory obstacles, and obtaining funding. Evidence-based botanical
      research can help to validate traditional uses and to facilitate new drug
      development. Concerted efforts of governmental agencies and industry are
      essential to ensure continuance of high-quality botanicals research.

PMID- 18638692
TI  - The value of acupuncture in cancer care.
AB  - Clinical research on acupuncture in cancer care is a new and challenging field in
      oncology. The results of clinical research will continue to provide clinically
      relevant answers for patients and oncologists. The evidence currently available
      has suggested that acupuncture is a safe and effective therapy to manage cancer
      and treatment related symptoms, while giving patients the ability to actively
      participate in their own care plan. The article explains the potential benefits
      of acupuncture and describes the difficulties in studying its effectiveness.

PMID- 18638695
TI  - From studying patient treatment to studying patient care: arriving at
      methodologic crossroads.
AB  - Cancer care is multifactorial and patient centered. It can be described as a
      complex package of interventions, delivered at different times and places with
      different intentions, which interacts and cannot be evaluated in isolation. The
      authors discuss the evolving nature of cancer care and address the challenges
      faced by biomedical research methodology when applied to cancer care. In
      addition, they identify new research directions to meet these challenges. These
      include qualitative research, mixed methods research, and approaches based on
      systems thinking.

PMID- 18638696
TI  - Mind-body medicine and cancer.
AB  - Mind-body medicine, grounded in a respectful, therapeutic partnership, should be
      a central element in the care of every person diagnosed with cancer. This article
      reviews some of the physiologic foundations of mind-body medicine, the
      introduction of mind-body approaches to cancer care in the 1970s, the specific
      mind-body approaches that have been used, and the evidence that supports their
      use. The importance of group support for enhancing the effectiveness of these
      approaches is discussed. Guidelines are offered for integrating mind-body
      approaches and perspectives in the care of people who have cancer.

PMID- 18638697
TI  - Practical hypnotic interventions during invasive cancer diagnosis and treatment.
AB  - Novel advances in biotechnology and medical imaging techniques have enabled an
      evolution toward earlier diagnosis and treatment by way of "minimally invasive"
      surgical techniques performed on the conscious patient without the use of general
      anesthesia. Although the risks of diagnostic and therapeutic interventions have
      been reduced with these approaches, patients still face many physical and
      psychologic challenges. Several randomized controlled trials have shown that
      hypnotic techniques are effective in reducing pain, anxiety, and other symptoms;
      in reducing procedure time; and in stabilizing vital signs. The benefits of
      adjunctive hypnotic treatments come at no additional cost. Patients, health care
      providers, hospitals, and insurance companies are advised to take advantage of
      hypnotic techniques.

PMID- 18638698
TI  - Incorporating complementary and integrative medicine in a comprehensive cancer
      center.
AB  - This article provides a model of integrating complementary and integrative
      medicine into cancer care in a comprehensive conventional cancer center. This
      model requires a patient-centered approach with attention to patients' concerns
      and enhanced communication skills. A discussion of patients' psycho-social
      spiritual perspectives is a crucial component in this approach. In addition,
      complementary and integrative medicine practitioners and conventional
      practitioners' involvement and cooperation in developing this integration process
      are essential. This process requires tremendous team effort, institutional
      culture change, trust and open communication between all members of the health
      care team, and support from institutional leaders.

PMID- 18638699
TI  - Ethical issues in integrative oncology.
AB  - Integrative oncology relates to an emerging dialog between complementary and
      alternative medicine (CAM) scholars, oncologists, family practitioners, and other
      health care providers who envision an extended and holistic patient-centered
      approach to oncology care. The multiple commitments of integrative oncology to a
      medical humanistic approach and to a strong evidence-based foundation may impose
      considerable ethical concerns and dilemmas. The authors use narrative ethics to
      present a case study that exemplifies the ethical challenges confronting
      physicians and health care providers who wish to provide an integrative approach
      for their patients. An ethical analysis of the narrative is provided to help
      clarify the ethical issues and conflicts within it. Finally, a framework that may
      transform ethical constraints to a communication tool is proposed.

PMID- 18638700
TI  - Remarkable recoveries: research and practice from a patient's perspective.
AB  - Mind-body therapies are often portrayed in the literature as self-palliative,
      adjunctive, and complementary, but rarely as contributive to cure. Many
      physicians continue to view them as acceptable indulgences so long as they are
      harmless and the patient remains fully compliant with a standard treatment
      regimen. The possibility that such modalities might help drive the healing
      process itself is infrequently acknowledged. This article addresses the topic of
      such therapies, examining remarkable recoveries in cancer, and suggesting the
      need for a "Remarkable Recovery Registry" to expand the literature on these
      cases. The author discusses the importance of complementary alternative medicine,
      and emotional and pyschologic support in the treatment regimen, and the need for
      health care providers and patients to work together to provide the best emotional
      environment for the healing process.

PMID- 18638701
TI  - Practicing a medicine of the whole person: an opportunity for healing.
AB  - Integrative medicine has been defined in several ways. For some it is a
      discipline that combines such approaches to the resolution of disease as
      acupuncture and homeopathy, meditation and imagery with more familiar and
      accepted health practices, such as surgery, pediatrics, and oncology. For others
      it is about cultivating awareness and sensitivity beyond symptoms to the mental,
      emotional, and spiritual needs of the patient. But, integrative medicine is more
      than the weaving together of techniques, or understanding the intimate
      interaction of the mental, emotional, and spiritual dimensions of human
      experience. It is about rethinking the task of medicine and the infrastructure of
      relationships and beliefs that have limited its power to serve all people.

PMID- 18638702
TI  - The globalization of ayahuasca: harm reduction or benefit maximization?
AB  - Ayahuasca is a tea made from two plants native to the Amazon, Banisteriopsis
      caapi and Psychotria viridis, which, respectively, contain the psychoactive
      chemicals harmala alkaloids and dimethyltryptamine. The tea has been used by
      indigenous peoples in countries such as Brazil, Ecuador and Peru for medicinal,
      spiritual and cultural purposes since pre-Columbian times. In the 20th century,
      ayahuasca spread beyond its native habitat and has been incorporated into
      syncretistic practices that are being adopted by non-indigenous peoples in modern
      Western contexts. Ayahuasca's globalization in the past few decades has led to a
      number of legal cases which pit religious freedom against national drug control
      laws. This paper explores some of the philosophical and policy implications of
      contemporary ayahuasca use. It addresses the issue of the social construction of
      ayahuasca as a medicine, a sacrament and a "plant teacher." Issues of harm
      reduction with respect to ayahuasca use are explored, but so too is the corollary
      notion of "benefit maximization."

PMID- 18638703
TI  - Sexual health risk among dance drug users: cross-sectional comparisons with
      nationally representative data.
AB  - AIMS: To describe the sexual behaviour and related risk of a sample of dance drug
      users and compare this with data from the UK National Survey of Sexual Attitudes
      and Lifestyles 2000 survey. METHODS: Cross-sectional purposive sampling using
      both self-completion postal and web-based questionnaires. FINDINGS: This sample
      of dance drug users are more sexually active and have more concurrent partners
      than the general population. Rates of anal or vaginal sex within the last year
      without condom use are high and of concern (men 80 per cent; women 90 per cent).
      These dance drug users appear also to have higher lifetime prevalence of sexually
      transmitted infections than the general population and are also more likely to
      have ever attended a sexual health clinic. CONCLUSIONS: Clubbing and dance drug
      use, as part of a socially active lifestyle, is associated with elevated and
      pronounced sexual health risk. Future epidemiological studies of sexual health
      risk should incorporate investigation of both clubbing and recreational drug use
      in order to confirm the representativeness of these observations. Clubbers should
      be considered a target for dedicated sexual health promotion interventions, which
      may also be combined with interventions targeting drug and alcohol use.

PMID- 18638704
TI  - The changing epidemiology of prevalent diagnosed HIV infections in Taiwan, 1984
      2005.
AB  - By the end of 2005, there were 10,158 reported cases of HIV infections in Taiwan,
      of them, 2,403 had developed full blown AIDS, and 1,333 had died. It represented
      an average annual increase of 15% in HIV diagnoses before 2003. The most common
      route of transmission is through men having sex with men followed by heterosexual
      contact, while infections through injecting drug use (IDUs) remained low.
      However, the number of newly reported HIV infections has been rising sharply
      since 2003, mainly among IDUs. The consequences of this HIV/IDU epidemic include
      a rapid increase in female HIV/AIDS patients and a decreased mean age of HIV/AIDS
      cases. Only 2% of patients in the IDU group have been diagnosed with AIDS,
      suggesting that most IDU cases are in the early stage of HIV infections. HIV/AIDS
      patients are provided with free medical care by the government in Taiwan,
      including anti-retroviral treatment. The case fatality rate of AIDS cases
      declined gradually from 64% in 1996 to 8.9% in 2005. Patients in the IDU group
      seek medical care less frequently than patients in the sexual contact group.
      Statistics show that 61.4% of patients in the IDU group did not seek HIV-related
      medical care, significantly higher compared to the sexual contact group. The
      Taiwanese government implemented a trial "Harm Reduction Programme," which
      involved a needle-syringe programme (NSP) and substitution treatment, in August
      2005. After 1 year's pilot study, the HIV incidence in cities with NSP decreased
      from 13.9 to 13.3 per 100,000 persons compared to an incidence increase from 11.5
      to 15.3 per 100,000 persons in cities without NSP. We scaled up the programme to
      cover the whole of Taiwan in July 2006 and are expecting to see the efficacy in
      the near future.

PMID- 18638705
TI  - Documenting practices and perceptions of 'safer' crack use: a Canadian pilot
      study.
AB  - BACKGROUND: People who smoke crack cocaine have a distinct social profile when
      compared to other drug user groups (e.g., injection drug users), may be at
      increased risk for particular health problems and experience unique social harms
      as a consequence of their crack use. In particular, they are exposed to dangers
      associated with unsafe crack pipe use and lack resources to enable safer
      consumption practices. The objectives of this pilot study were to determine the
      current practices of people who smoke crack in Vancouver and to discover common
      attitudes towards the modification of crack smoking practices in the direction of
      safer crack use. METHODS: Members of a community coalition administered a short
      survey to street-entrenched crack cocaine users regarding their smoking
      equipment, their current crack smoking practices, the physical consequences of
      smoking crack and their attitudes towards safer crack use. RESULTS: Most
      respondents engaged in 'unsafe' crack use practices and experienced harmful
      consequences associated with crack use. Those who shared their equipment were at
      higher risk for experiencing these harmful consequences. CONCLUSION: The
      information from this study suggests that strategies aimed at reducing the harms
      associated with crack use, as well as safer crack use education and programming,
      should be incorporated into substance misuse interventions, disease prevention
      and health promotion policy, and that further research about these issues is
      needed.

PMID- 18638706
TI  - Why some injection drug users lick their needles: a preliminary survey.
AB  - BACKGROUND: Injection drug users (IDUs) with poor hygiene practices are at risk
      for infection with their commensal flora. One example of a poor hygiene practice
      is licking the needle prior to injecting the drug. There are few published
      reports addressing the proportion of IDUs who lick their needles prior to
      injection and no prior studies evaluating the reasons for this practice. METHODS:
      We conducted face-to-face interviews with 40 IDUs admitted to the internal
      medicine service at our institution. We collected data regarding whether the
      subject licked the needle before injecting drugs, whether the subject licked the
      injection site before or after injecting drugs, and the reasons they report for
      doing so. RESULTS: Thirteen (32.5%, 95% CI, 18.6-49.1) of 40 subjects reported
      licking their needles prior to injecting. Reasons included ritualistic practices,
      cleaning the needle, enjoying the taste of the drug, checking the "quality" of
      the drug, and checking that the needle was in usable condition. CONCLUSIONS: In
      our study, approximately one-third of IDUs licked their needles prior to
      injecting. More data are needed to demonstrate whether the practice of needle
      licking significantly increases a person's risk for infection with oropharyngeal
      flora. Medical providers should ask patients about specific practices surrounding
      injection drug use, and educate drug users about avoiding unhygienic injection
      practices.

PMID- 18638707
TI  - Do that to me one more time! What kind of trial replications do we need?

PMID- 18638708
TI  - Reproducibility of dwarf pea shoot growth stimulation by homeopathic potencies of
      gibberellic acid.
AB  - OBJECTIVES: Investigation of the conditions for reproducibility of dwarf pea
      shoot growth stimulation through homeopathic potencies of gibberellic acid.
      METHODS: 4 batches of pea seed (Pisum sativum L. cv. Fruher Zwerg; harvests from
      1997, 1998, 1999, and 2000) were tested regarding their reaction to gibberellic
      acid 17x and 18x (compared to unsuccussed and succussed water (1x) as controls)
      in 8 independent randomized and blinded experiments. Pea seed was immersed for
      24h in watery solutions of homeopathic potencies or controls, and cultivated
      under controlled laboratory conditions. Pea shoot length was measured after 14
      days. Two systematic negative control experiments assessed the stability of the
      experimental set-up. RESULTS: The systematic negative control experiments yielded
      no significant effects and confirmed the stability of the experimental set-up. 2
      out of 4 seed batches reacted to the homeopathic treatment (p<0.05). Seed batch
      1997 showed a reproducible reaction to gibberellic acid 17x (shoot length
      stimulation of +11.2%, p=0.007), and seed batch 1998 showed a significant varying
      response (increase/decrease). Seed batch 1997 differed from the other 3 batches
      by an increased glucose and fructose content, and reduced 1000kernel weight. Meta
      analysis with data of earlier experiments is in accordance with the results of
      the present experimental series. CONCLUSIONS: We identified 'seed quality' as a
      possible trigger factor for successful reproducibility in homeopathic basic
      research. Premature harvesting as a possible key factor for responsiveness of
      dwarf peas to homeopathic potencies of gibberellic acid is our current working
      hypothesis to be tested in future experiments.

PMID- 18638709
TI  - The effect of QuYuHuaTanTongLuo Decoction on the non-alcoholic steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) is the most common cause of cryptogenic
      cirrhosis, is becoming more prevalent in China. However, there is as yet no
      clearly established therapy for reversing fatty liver. Our aim is to explore the
      effect of traditional Chinese herbs QuYuHuaTanTongLuo Decoction (QYHTTLD) on non
      alcoholic steatohepatitis. Sixty-nine non-alcoholic steatohepatitis patients were
      randomly divided into two groups. One group of 35 patients were treated by
      QYHTTLD, another group of 34 patients were treated by Ursodeoxycholic acid
      (UDCA). The TNF-alpha, IL-8, MDA level, SOD activity and liver function, as well
      as B ultrasonic image were detected before and after being treated. The results
      showed: after 6 months treatment, MBI of the treatment group was obviously
      decreased (p<0.05). The levels of TC, TG and LDL-C were significantly decreased
      whereas the level of HDL-C increased (p<0.01, p<0.05, p<0.05, and p<0.05,
      respectively) in the treatment group, the levels of TC, TG, LDL-C and HDL-C had
      no significant difference in the control group (p>0.05). The levels of TNF-alpha,
      IL-8 and MDA were significantly decreased whereas SOD activity was significantly
      increased (p<0.01, p<0.05, p<0.01, and p<0.01, respectively) in the treatment
      group, the level of MDA was significantly decreased in the control group
      (p<0.05). B ultrasonic images were ameliorated in different degree (p<0.01 and
      p<0.01, respectively). Both QYHTTLD and UDCA had the effect in improving the
      scores of symptoms and signs of patients, however, the difference value of the
      scores in treatment group were significantly higher than that in control group
      after being treated for 6 months (p<0.05). CONCLUSION: QYHTTLD is effective for
      treating non-alcoholic steatohepatitis, and its effect seems to relate with the
      ways of QYHTTL down-regulating inflammation cytokine IL-8 level and relieving
      lipid peroxidation of liver.

PMID- 18638710
TI  - A survey of the uptake and implementation of research evidence by South
      Australian acupuncturists in clinical practice: attitudes and associated
      predictive factors.
AB  - OBJECTIVE: To examine South Australian acupuncturists' attitudes towards the use
      of research evidence and concurrently identify predicative factors associated
      with the uptake and implementation of research evidence. METHODS: Questionnaires
      were mailed out to the entire South Australian acupuncturist population (n=94).
      The population was divided into two groups, medical acupuncturists (general
      practitioners or other medical specialists) and non-medical acupuncturists, as
      previous studies have suggested that clinicians' attitudes to EBP are particular
      to the clinical setting. RESULTS: The total response rate to the survey was 76.6%
      (n=72). The difference in response rates between non-medical acupuncturists
      (90.9%, n=60) and medical acupuncturists (42%, n=12) was significant (p<0.0001).
      Over half of all respondents had both prior research training and previous
      research experience. Both groups held positive attitudes to research utilization,
      the use of research information was considered to be an important component of
      their professional practice, although they prioritized patient care over both
      reading research evidence and undertaking primary research. There was no
      significant difference in research interest between groups. The only predicative
      factor that influenced research utilization was related to the non-medical
      acupuncturists period of time in practice; non-medical acupuncturists interest in
      research (rho=-0.29, p=0.036) declined as they accrued clinical experience. No
      predictive factors were identified for the medical acupuncturist group.
      CONCLUSION: South Australian acupuncturists hold favorable views towards research
      utilization and consider the integration of research evidence into clinical
      practice as an important component of professional development. Professional
      associations should implement strategies which capitalize on the respondents'
      positive attitudes in order to ensure high quality evidence-based care for
      patients seeking acupuncture.

PMID- 18638711
TI  - Differential effect on symptoms treated with traditional Chinese medicine and
      western combination therapy in RA patients.
AB  - OBJECTIVE: This study is designed to compare the therapeutic effects and safety
      of traditional Chinese medicine (CM) therapy and western combined therapy (WM) in
      the treatment of rheumatoid arthritis (RA). METHODS: After 24 weeks' treatment,
      the efficacy, safety and the improvement on symptoms of traditional Chinese
      medicine in 199 patients and western medicine therapy in 197 patients of RA were
      analyzed. CM therapy included Glucosidorum Tripterygll Totorum tablet and Yishen
      Juanbi Tablet. The WM therapy included voltaren extended action tablet,
      methotrexate and sulfasalazine. The American College of Rheumatology (ACR) 20, 50
      and 70 responses were employed as primary end-point analysis and the 18 symptoms
      as secondary end-point analysis. All data were analyzed on SPSS11.5 statistical
      package. RESULTS: The ACR20 and ACR50 responses in WM were higher than in CM
      group, but more improvement on the symptoms and less adverse events were observed
      in CM therapy. The 18 CM symptoms in RA could be grouped into four symptom
      combinations with factor analysis method. The factor loading value difference
      (which reflects the degree of improvement) in responded cases was lower than in
      non-responded cases in the symptom combination 1. The loading value difference in
      both responded and non-responded cases in CM treated patients were higher than
      those in WM treated group in the symptom combination 2 and 3. CONCLUSIONS: WM
      combined therapy was more effective in the treatment of RA in ACR20 evaluation,
      but more improvement on CM symptoms were seen in the CM therapy.

PMID- 18638712
TI  - Familiarity breeds discontent: senior hospital doctors' attitudes towards
      complementary/alternative medicine.
AB  - Studies have shown that many general medical practitioners refer their patients
      to complementary/alternative medicine (CAM) practitioners and believe in the
      therapeutic benefit of these modalities. However, there is less information
      concerning the beliefs and practices of senior hospital doctors. OBJECTIVES: In
      view of the increasing institutionalization of CAM and moves to incorporate CAM
      into secondary and tertiary healthcare settings, the objective of this study is
      to understand the attitudes and practices of senior hospital doctors, a sector
      whose members are often responsible for formulating and implementing
      institutional policy. DESIGN AND SETTING: A questionnaire was administered to 294
      directors of hospital departments and their deputies on their attitudes and
      practices concerning CAM. Response rate was 70%. Almost all general hospitals in
      Israel participated in the study. RESULTS: The findings show, in general, that
      while senior hospital physicians in Israel hold positive attitudes towards CAM,
      they are not well disposed towards co-operation with CAM practitioners.
      Incorporating a CAM clinic into the hospital site does not seem to enhance
      clinical co-operation between conventional physicians and CAM practitioners. In
      hospitals that had functioning CAM clinics, doctors were consistently and
      significantly more opposed to co-operation with CAM than in hospitals without CAM
      clinics.

PMID- 18638713
TI  - Use of complementary and alternative medicine by patients with cluster headache:
      results of a multi-centre headache clinic survey.
AB  - OBJECTIVES: To evaluate the rates, pattern, satisfaction with, and presence of
      predictors of complementary and alternative medicine (CAM) use in a clinical
      population of patients with cluster headache (CH). DESIGN AND SETTING: One
      hundred CH patients attending one of three headache clinics were asked to undergo
      a physician-administered structured interview designed to gather information on
      CAM use. RESULTS: Past use of CAM therapies was reported by 29% of the patients
      surveyed, with 10% having used CAM in the previous year. Only 8% of the therapies
      used were perceived as effective, while a partial effectiveness was reported in
      28% of CAM treatments. The most common source of recommendation of CAM was a
      friend or relative (54%). Approximately 62% of CAM users had not informed their
      medical doctors of their CAM use. The most common reason for deciding to try a
      CAM therapy was that it offered a "potential improvement of headache" (44.8%).
      Univariate analysis showed that CAM users had a higher income, had a higher
      lifetime number of conventional medical doctor visits, had consulted more
      headache specialists, had a higher number of CH attacks per year, and had a
      significantly higher proportion of chronic CH versus episodic CH. A binary
      logistic regression analysis was performed and two variables remained as
      significant predictors of CAM use: income level (OR=5.7, CI=1.6-9.1, p=0.01), and
      number of attacks per year (OR=3.08, CI=1.64-6.7, p<0.0001). CONCLUSION: Our
      findings suggest that CH patients, in their need of and quest for care, seek and
      explore both conventional and CAM approaches, even though only a very small
      minority finds them very satisfactory.

PMID- 18638714
TI  - An examination of the clinical practices and perceptions of professional
      herbalists providing patient care concurrently with conventional medical practice
      in Australia.
AB  - OBJECTIVE: To examine the clinical practices and perceptions of herbalists
      providing patient care concurrently with conventional medical practice. METHOD: A
      postal survey was sent to all full members of the National Herbalists'
      Association of Australia (NHAA). There were 649 members in practice at the time
      of the survey and the total response rate was 58.2%. RESULTS: Most of the
      patients who visit professional herbalists seek care for chronic conditions have
      been medically diagnosed and continue to consult a general practitioner (GP).
      Study findings indicate that many patients who visit herbalists are taking herbal
      and pharmaceutical medicines concurrently. Therapists reported a high rate of
      referral to GPs for medical diagnosis, treatment and/or prescription. The
      majority of herbalists also routinely include a pharmaceutical case history as
      part of their consultation and patients are encouraged to inform their GPs if
      they are taking any herbal therapies. The majority of herbalists reported a need
      for closer collaboration and cooperation with the medical community in the
      future. CONCLUSION: Herbalists in Australia are fully aware of the value of
      medical diagnosis and inter-referrals, are well informed about patient
      medications and require a closer working relationship with the medical community.
      Further research is needed to investigate potential interactions between herbal
      and pharmaceutical medicines to maintain high safety standards for the public.

PMID- 18638715
TI  - Are acupuncture-type interventions beneficial for correcting breech presentation?

PMID- 18638717
TI  - Role of receptor heterodimers in the development of L-dopa-induced dyskinesias in
      the 6-hydroxydopamine rat model of Parkinson's disease.
AB  - Chronic L-dopa administration is associated with development of dyskinesias. The
      molecular mechanisms of these side-effects, however, remain elusive. Dopamine
      (DA) receptors interact with other receptors to form highly organized complexes
      where their activity is finely tuned by several proteins. The DA D1R forms a
      heteromeric complex with the NMDA receptor (NMDAR) and this interaction
      influences the trafficking of both receptors. Using the 6-hydroxydopamine rat
      model of Parkinson's disease, we report a correlation between the development of
      L-dopa-induced dyskinesias and changes in synaptic D1R/NMDAR complexes.

PMID- 18638718
TI  - Investigation of the complexity of barley stripe mosaic virus RNAs with
      recombinant dna clones.
AB  - RNA isolated from the Type, ND18, and Norwich strains of barley stripe mosaic
      virus (BSMV) was electrophoresed in agarose gels, transferred to nitrocellulose,
      and hybridized with BSMV-specific complementary DNA (cDNA) or recombinant DNA
      clones derived from ND18 RNA. Genomic RNA components 1 (Mr = 1.43 x 10(6)) and 2
      (Mr = 1.24 x 10(6)) were resolved in all three strains, but RNA 3 (Mr = 1.1 x
      10(6)) was seen only in the ND18 and Norwich strains. A low-molecular-weight RNA
      (Mr = 0.27 x 10(6)), thought to be a subgenomic (SG) RNA, was also detected in
      RNA preparations from all three strains by staining with toluidine blue or
      ethidium bromide and by hybridizing with cDNA or selected recombinant DNA probes.
      Three classes of recombinant DNA clones, designated pBSM1, pBSM2, and pBSM3, were
      identified by hybridization of nick-translated recombinant DNA to
      electrophoretically separated viral RNAs. Clones in the pBSM1 class hybridized
      only to RNA 1 of all three strains and class pBSM2 clones hybridized only to RNA
      2 of all three strains. Class pBSM3 clones hybridized to RNA 3 of the ND18 and
      Norwich strains and to RNA 2 of the Type strain, but not to RNA 2 of ND18 or
      Norwich. Based on the sizes of the BSMV-specified inserts in clones designated
      pBSM1a, pBSM2a, and pBSM3a, we estimate that a minimum of 44, 63, and 63% of the
      nucleotide sequences of ND18 and Norwich RNAs 1, 2, and 3, respectively, are
      unique. Furthermore, because the combined size of the inserts in pBSM2a and
      pBSM3a is approximately 15% greater than the estimated size of RNA 2, it is
      probable that the second RNA component of the Type strain actually consists of
      two RNA species which are similar in size but have different sequences. The SG
      RNA component is viral specific and contains sequences common to clones derived
      from RNA 3.

PMID- 18638716
TI  - The reemergence of nitric oxide and cancer.

PMID- 18638719
TI  - Editorial.

PMID- 18638720
TI  - Skull base chordomas: presentation of six cases and review of the literature.
AB  - Chordomas are uncommon tumours occuring from remnants of the notochord. They are
      mainly localized in the sacrococcygium, the spine and the skull base. We focused
      our study on skull base chordomas and reviewed 531 published cases and 6 cases
      diagnosed in our institution. The six cases diagnosed at our hospital are
      described with a special mention of a unique case presenting with meningitis.
      Clinical features, radiology, histopathology and survival with different
      treatments are reviewed. Skull base chordomas can occur at any age and are
      slightly more frequent in males. Patients complain most often of diplopia and
      headaches. Abducens nerve palsy is the commonest neurological finding.
      Radiological examination should include both CT-scan which shows extensive
      osteolysis, calcifications and contrast enhancement and MRI for topographical
      definition. Metastases rarely occur. Treatment remains controversial but combined
      surgery and radiotherapy is the best treatment with a 5 year survival rate of
      75%.

PMID- 18638721
TI  - A review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage Part I:
      Incidence and effects.
AB  - Delayed ischaemia due to cerebral 'vasospasm' is a significant cause of morbidity
      and mortality after aneurysm haemorrhage. In a literature review more than 30 000
      cases were found where vasospasm after subarachnoid haemorrhage (SAH) was
      discussed. The incidence of angiographic vasospasm was 43.3% overall, and 67.3%
      where angiography was done at a time of maximum expected spasm. Symptomatic
      vasospasm or delayed ischaemic deficit (DID) occurred in 32.5%. There was no
      difference in incidence and time course between preoperative and postoperative
      cases. 30% of those with DID died, and permanent neurological deficits occurred
      in 34%. A fatal outcome was much more likely in the presence of vasospasm, and a
      satisfactory outcome one third less likely. Vasospasm is thus the cause of death
      in about 10%, and of disability in slightly more cases of aneurysmal SAH. The
      extent of the problem has not changed significantly over three decades.

PMID- 18638722
TI  - Ethics, brain damage and ending lives.
AB  - The problem of patients in the persistent vegetative state is beset by complex
      ethical and philosophical issues to do with the nature of persons and our ethical
      duties towards them. Many discussions obscure the main ethical considerations. In
      this paper, I approach the problem through a philosophical analysis of the
      concept of a person and the attributes that ground our ethical responsibilities
      to persons. I argue that we are under no ethical obligation to continue
      lifesustaining treatment for patients properly diagnosed as being in the
      persistent vegetative state or with other severe brain damaged conditions. This,
      of course, is compatible with our trying to do our best for such patients until
      the prognosis is clear.

PMID- 18638723
TI  - Astrocytoma resection using an interactive frameless stereotactic wand: an early
      experience.
AB  - 18 patients with varying grades of astrocytoma had tumour resection using a new
      frameless, interactive sterotactic localizing wand. The system enables localizing
      information to be presented to the operator in multiple two-dimensional or three
      dimensional displays in real time. In all cases the wand was used to help outline
      tumour boundaries in an attempt to resect solid tumour completely. Other uses
      included placing a minimal craniotomy or modifying an existing craniotomy in 17
      (94%) patients, for intraoperative physiologic mapping in 2 (11%) and electrode
      placement in 1 (6%). All patients had a complete (98-100%) resection by
      postoperative MRI, and in 8 (44%) the tumour was removed from eloquent areas.
      Evaluation at approximately 6 weeks after surgery showed that 3 (16%) were
      improved, 14 (78%) were the same, and 1 (6%) was worse. On the second
      postoperative day no patient was better than their preoperative status, 10 (56%)
      were the same, and 8 (44%) patients were clinically worse. At 3 months the
      figures were 2 (11%), 11 (61%), and 4 (22%) respectively, and 1 patient had
      expired. The extent of resection has been shown to be an important prognostic
      factor in both low and high grade astrocytomas. This system allows accurate
      volumetric near en bloc resection and this was achieved in 17 (94%) cases. In one
      case of hippocampal tumour the tumour was removed in a piecemeal fashion. This
      system is an effective low cost alternative to frame volumetric systems and is
      associated with minimal morbidity at 6 weeks.

PMID- 18638724
TI  - Seizure outcome and pathological findings following temporal lobectomy in
      patients with complex partial seizures and foreign tissue lesions seen only on
      MRI.
AB  - 11 patients with foreign tissue lesions (FTL) in the temporal lobe associated
      with complex partial seizures (CPS) were studied. All had lesions clearly
      definable on magnetic resonance imaging (MRI) but not seen on computerised
      tomographic (CT) scans. All cases showed seizure reduction following temporal
      lobectomy with 10 becoming seizure free. Pathology showed 9 tumours, 1 hamartoma
      and 1 cavernous angioma. Hippocampus was available for examination in 7 cases,
      showing abnormalities in 6. Our findings suggest MRI be mandatory in screening
      patients with CPS and that following surgery, outcome should be excellent.

PMID- 18638725
TI  - Intra-arterial papaverine in the management of cerebral vasospasm following
      subarachnoid haemorrhage.
AB  - Between July 1992 and January 1993 a prospective pilot study of the efficacy of
      intra-arterial papaverine in the management of clinically significant
      angiographically confirmed cerebral vasospasm arising as a consequence of
      aneurysmal subarachnoid haemorrhage was conducted. During this period 40 patients
      were managed with aneurysmal subarachnoid haemorrhage. All patients were treated
      with nimodipine from day of admission and carefully monitored in the
      neurosurgical intensive care unit. 11 of the 40 patients subsequently developed
      clinically significant angiographically confirmed cerebral vasospasm and
      underwent angiography with selective internal carotid or vertebral artery
      injection of papaverine in 12 to 40 mg boluses to a maximum of 450 mg. A good
      angiographic response was seen in all cases. Two patients underwent repeat
      procedures, in one case twice. Overall clinical outcome was good in 7 cases,
      moderate disability in 2 cases, severe disability in 1 case and death in 1 case.
      In patients who underwent the procedure in less than 4 hours from the onset of
      their deficits (n=8) a good outcome was seen to occur in 7 patients with one
      patient sustaining a moderate deficit. Complications from the procedure were
      seizures in 3 patients and a momentary locked-in-syndrome in one case. All
      complications were seen with a fast bolus of the higher volume papaverine and
      have not occurred with a slow infusion of the lower dose boluses. None of the
      patients developing these complications had them recur outside the angiogram
      suite. Our conclusion is that this form of treatment supplements the therapeutic
      regimens now available in the management of cerebral vasospasm.

PMID- 18638726
TI  - Antitumour effect of MX2, a new morpholino anthracycline against C6 glioma cells
      and its cytotoxic effect in combination with photodynamic therapy.
AB  - MX2, a novel lipophilic morpholino anthracycline, has been reported to have
      superior chemotherapeutic effects to Adriamycin (ADM) against murine and human
      tumour cells. In this study the chemotherapeutic effect of MX2 against C6 glioma
      cells in vitro and in vivo was examined as well as the photocytotoxicity of MX2
      and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. The
      drug concentration required for 50% inhibition of cell growth (IC50) of MX2 for
      C6 glioma cells was 6.5 +/- 1.0 ng/ml, which was lower than for ADM and
      nitrosourea (ACNU). The growth of C6 glioma cells inoculated intracerebrally in
      mice was inhibited by intravenous (iv) injection of MX2 at doses ranging from 1.0
      3.0 mg/kg suggesting that MX2 may be clinically effective against human malignant
      gliomas. Mild photocytotoxicity of MX2 against C6 cells in vitro was observed at
      high concentrations of MX2 illuminated with white light but not red light (> 630
      nm). In combination, MX2 and the photosensitizer haematoporphyrin derivative
      (HpD) resulted in cyto- and photo-toxicity of C6 glioma cells irrespective of
      whether the cells were treated with MX2 either immediately after red light
      illumination following incubation with HpD, or at an interval of 24 hours before
      incubation with HpD. We conclude that MX2 may be clinically useful against
      malignant glioma alone, and in combination with other therapies such as PDT.

PMID- 18638727
TI  - Expression of interleukin-6 gene in human astrocyte cell lineages.
AB  - Expression of the lymphokine genes in human astroglial cell lineages was studied.
      Primers for 7 different human lymphokines, from interleukin-1a (IL-1a) to
      interleukin-6 (IL-6), were used to analyze RNA transcripts in 5 cultured human
      astrocytoma cell lines and 9 brain specimens by polymerase chain reaction (PCR).
      Two out of 5 unstimulated astrocytomas, U138MG and U373MG, expressed IL-6 genes.
      After stimulation with IL1beta, all astrocytoma and one neuroblastoma cell lines
      expressed IL-6 genes, but other leukemic cell lines did not show RNA transcripts
      of IL-6. In addition to the cultured cells, we examined IL-6 gene expression
      within human malignant astrocytoma, peritumoural brain and autopsied normal
      brains. The result shows that tumour and cells of the surrounding reactive lesion
      express IL-6 genes, but it is not expressed in normal brains. Next, the
      concentration of IL-6 in the supernatant of cultured cells was measured
      quantitatively by sandwich immunoassay, ELISA. IL-6 activity was present, but low
      in all astrocytomas with the exception of A172. Furthermore, the concentration of
      IL-6 increased markedly with the stimulation of IL-1beta in both a time- and dose
      dependent fashion. A172 could also produce IL-6 as was seen in gene expression.
      From these results, it is suspected that astroglial cell-derived IL-6 may
      participate in local immune reactions accompanying infection, degeneration and
      malignancies in the central nervous system.

PMID- 18638728
TI  - Effects of intrathecal administration of nicardipine and nifedipine on chronic
      cerebral vasospasm in dogs.
AB  - Chronic cerebral vasospasm after subarachnoid haemorrhage (SAH) responds poorly
      to systemic administration of dihydropyridine calcium antagonists. However, the
      spastic arteries can be dilated by the topical (intrathecal) administration of
      the drugs. We examined by angiography the spasmolytic effects of intrathecal
      (cisternal) administration of nicardipine (0.1 mg 1 ml ) or nifedipine (0.1 mg 1
      ml ) on day 7 of SAH made by the two-haemorrhage model in dogs. Both drugs
      dilated the spastic basilar artery from 15 min till 4 hours after the drug
      administration. The increase in the diameter of the basilar artery between 1 and
      3 hours was statistically significant in both groups. Intrathecal administration
      of nicardipine which is water soluble, may be useful in the treatment of chronic
      cerebral vasospasm in patients.

PMID- 18638729
TI  - Multiple aneurysms associated with bilateral carotid occlusion and venous
      angioma: surgical management risk-case report.
AB  - A unique case of multiple aneurysms associated with bilateral carotid artery
      occlusion and venous angioma is described. A 42 year old female presented with
      subarachnoid haemorrhage. Cerebral angiograms demonstrated(1) a ruptured saccular
      aneurysm in the right posterior cerebral artery,(2) bilateral occlusion of
      internal carotid arteries,(3) a rete mirabile in the subtemporal fossa fed by
      left external carotid artery which connected with the internal carotid artery at
      the cavernous portion where a saccular aneurysm had formed, and(4) a venous
      angioma in the posterior fossa. The ruptured aneurysm of the posterior cerebral
      artery was obliterated preserving the anterior choroidal arteries. However, a
      left hemiparesis developed and CT scan revealed a small low density area in the
      right posterior limb of the internal capsule postoperatively. A ruptured aneurysm
      associated with bilateral extracranial carotid occlusion poses a clinical dilemma
      and treatment of such cases is challenging and difficult. The non-surgical and
      surgical outcomes of ruptured cerebral aneurysms associated with internal carotid
      occlusion are reviewed.

PMID- 18638730
TI  - Properties of turnip yellow mosaic virus in cesium chloride solutions: the
      formation of high-density components.
AB  - The bottom component B1a of TYMV with a buoyant density of 1.42-1.43 g/ml, is
      converted to a more dense particle B2a following CsCI density gradient
      centrifugation. This conversion is complete after a prior incubation of the virus
      in the CsCl solution at elevated temperatures. It is shown that the formation of
      B28 is accompanied with a loss from the virion of polyvalent cations like
      spermidine and Mg2+. The exchange of the latter ions for Cs ions is responsible
      for the occurrence of the higher-density particles. The more dense component B2a
      can be converted back to B,; like particles upon incubation in the presence of
      0.1 M M9Cl2. If TYMV or component B1a is centrifuged in the presence of Mg2+, the
      conversion into B2a is prevented. The latter phenomenon allowed the isolation and
      characterization of the minor components B1b and B1c, previously postulated
      (Mellema et al. (1979), Virology 96, 38-46). The phenomenon of conversion
      appeared to be restricted to the components of the B series of TYMV; indicating
      that the class of light minor components does not contain artefacts of the CsCl
      gradient centrifugation. The formation of B2a is accompanied by degradation of
      RNA, which might be due to some conformational change in the virion, rendering
      the RNA vulnerable to RNases.

PMID- 18638731
TI  - Structure of the Baculovirus nucleocapsid.
AB  - A low-resolution structural model of the nucleocapsid of Spodoptera litura
      granulosis virus, a member of the Baculoviridae family, has been determined using
      contrast variation methods in both electron microscopy and low-angle X-ray
      solution scattering. The cylindrical portion of the characteristic capsid surface
      is composed of a 12 start helix system of monomer subunits, giving rise to a
      relatively open stacked ring structure running parallel to the cylinder axis and
      repeating approximately every third ring. Structural proteins which appear
      distinct from those constituting the cylinder comprise the stacked ring-like
      assemblies which form caps at both ends of the nucleocapsid. Within the
      nucleocapsid the double-stranded closed loop of DNA associates heterogeneously
      with a highly basic polypeptide to form a cylindrical core. The basic protein is
      thought to participate in condensation and protection of the genome both prior to
      and during encapsidation.

PMID- 18638732
TI  - Properties of the nuclear polyhedrosis virus of the great wax moth: oligomeric
      circular DNA and the characteristics of the genome.

PMID- 18638733
TI  - Virus multiplication in tobacco protoplasts inoculated with tobacco mosaic virus
      RNA encapsulated in large unilamellar vesicle liposomes.
AB  - Tobacco mosaic virus RNA encapsulated in large unilamellar vesicles of
      phosphatidylserine was found to infect efficiently tobacco protoplasts prepared
      from suspension culture cells. Multiplication of tobacco mosaic virus in infected
      cells was confirmed by fluorescent antibody staining, electron microscopic
      observation, and infectivity assay. Virus infectivity was first detected at 6 hr
      after infection, it then increased rapidly and reached a plateau at 20 to 24 hr.

PMID- 18638734
TI  - Consent.

PMID- 18638735
TI  - A review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage Part II:
      Management.
AB  - This review examines prevention and treatment of delayed cerebral vasospasm after
      aneurysm haemorrhage, with emphasis on techniques for removal of cisternal blood,
      fluid loading and induced hypertension, and calcium antagonists. Most effective
      were fluids/hypertension and nimodipine, which reduced the incidence of DID by
      over half. Other drugs that may be useful are tissue plasminogen activator and
      the aminosteroids. A number of others have also been examined. For the treatment
      of DID, calcium antagonists, and fluid loading and hypertensive treatment are the
      most effective. Transluminal angioplasty is also proving to be useful. The
      combination of prophylaxis and treatment with fluids and nimodipine should reduce
      poor outcome resulting from vasospasm by two-thirds, from 21% untreated to less
      than 7%. In spite of the more or less proven efficacy of these measures, large
      numbers of cases are still being reported in whom no specific management is being
      used.

PMID- 18638736
TI  - The implications of Rogers v. Whitaker.

PMID- 18638737
TI  - Rogers v Whitaker: an ethical perspective.

PMID- 18638738
TI  - Carotid endarterectomy: indications and surgical technique.
AB  - Carotid endarterectomy is a therapeutic option for patients with symptoms of
      focal cerebral ischaemia, when it can be performed with a combined morbidity and
      mortality below the yearly risk of stroke (5%). The experience with 815 carotid
      endarterectomies performed from 1979 to 1992 is presented. There were 530 (65%)
      men and 285 (35%) women of ages from 34 to 82 (median 65); risk factors included
      diabetes mellitus 196 (24%), hypertension 554 (68%), and smoking 570 (70%).
      Clinical presentation consisted of transient ischaemic attacks 464 (57%),
      cerebral infarction with minimal neurological residual 228 (28%), stroke in
      evolution 2 (0.2%), and asymptomatic stenosis 121 (15%). According to Sundt's
      classification of medical risk groups, the patients fit the following grades:
      Grade I: 106 (13%), Grade II: 350 (43%), Grade III: 357 (44%), Grade IV: 2
      (0.2%). All patients received endotracheal anaesthesia with trans-operative
      monitoring of intra-arterial pressure, central venous pressure and arterial blood
      gases. Thiopental (3-5 mg/kg) and lidocaine (1 mg/kg) were given for induction
      and at 15 minutes intervals during carotid cross-clamping. Intraluminal shunts
      were used in 14 (2%). A conventional (open) endarterectomy was performed in 379
      (46%) and a limited endarterectomy (closed) in 436 (54%). Complications included
      8 (1%) deaths, 24 (3%) developed a major neurological deficit that persisted, 24
      (3%) had perioperative TIAs which resolved completely. Of the patients with
      preoperative neurological deficits, 32 (4%) recovered. Therefore, at one month
      after surgery, 782 (96%) were either as well or better than preoperatively. Of
      483 (59%) postoperative angiograms, 40 (5%) showed an internal carotid artery
      occlusion. Six of these patients developed an immediate postoperative cerebral
      infarction and one died. Non-neurologic complications were: cardiac 40 (5%),
      peripheral nerve 24 (3%), and local wound problems 16 (2%). A carotid
      endarterectomy can be performed safely when it is done with meticulous attention
      to detail and consistent surgical technique.

PMID- 18638739
TI  - Angiographic vasospasm in a contemporary series of patients with aneurysmal
      subarachnoid haemorrhage.
AB  - Over the last decade there have been significant changes in the management of
      patients with aneurysmal subarachnoid haemorrhage (SAH). Many of these changes,
      such as haemodilutional, hypervolaemic, hypertensive therapy and the use of
      calcium channel blockers, have been directed at the prevention and treatment of
      vasospasm. The angiograms of a contemporary series of 56 consecutive surgically
      treated patients with aneurysmal SAH were examined to compare angiographic
      vasospasm with that seen in historical studies. The time course of angiographic
      vasospasm was found to be broadly similar to that reported in previous studies,
      with onset after day 3 following SAH, maximal narrowing during the second week,
      and resolution after day 16. The times of peak narrowing and resolution were
      slightly earlier in previous studies. 30% of patients had clinical vasospasm
      (delayed neurological deficit for which other causes had been excluded), and
      these patients had a trend to more severe angiographic narrowing than those
      without clinical vasospasm, particularly in the second week following SAH. 44
      angiograms were performed between days 1-3 post SAH and repeated between days 4
      16. 95% of these showed arterial narrowing at the second angiogram. Patients not
      achieving an independent outcome tended to have had both more clinical vasospasm
      and more severe angiographic spasm than those achieving independence. It is
      concluded that angiographic vasospasm remains a common occurrence in the modern
      era, and continues to be associated with clinical events and a poor outcome.

PMID- 18638740
TI  - Craniofacial resection in the management of paranasal sinus cancer.
AB  - The prognosis for patients with cancer of the paranasal sinuses (PNC) has been
      very poor, mainly due to a high rate of local recurrence. We report a series of
      46 patients with PNC treated by craniofacial resection at the Royal Melbourne
      Hospital between November 1983 and June 1991. There has been no operative
      mortality or serious morbidity in these patients. The importance of a pericranial
      flap in the reconstruction of the floor of the anterior cranial fossa is
      emphasized. All patients have been followed to death or to the present time.
      There was a five year survival of 73% for squamous cell carcinoma and 83% for
      adenocarcinoma. This appears to represent a significant improvement in the long
      term results over conventional surgery and radiotherapy. The strong association
      between adenocarcinoma of the ethmoid sinuses and occupational exposure to
      hardwood dusts is borne out in our series. A history of prolonged wood dust
      exposure was given by all the 16 patients with adenocarcinoma and by 12 of the 25
      patients with squamous cell carcinoma.

PMID- 18638741
TI  - Prevention of infective complications of craniocerebral war wounds in Vietnam
      (1978-79).
AB  - Infective complications often occur after craniocerebral wounds caused by
      missiles. These dangerous sequelae are, in our experience, the chief cause of
      delayed death after injury. Initial contamination, the presence of retained bone
      and metal fragments acting as a nidus for microbial growth, and disturbances in
      cerebrospinal fluid (CSF) circulation, especially when the ventricular system is
      involved, are challenging problems in the management of missile wounds of the
      brain. We have analysed the significance of these factors in 295 cases of such
      wounds sustained in the war on the south-west border of Vietnam in 1978-79. In
      cases undergoing operation within 24 hours, the incidence of infection was 13.7%,
      rising to 31% when delay in excess of 72 hours after injury was unavoidable. We
      formed the opinion that the risk of infection was not significantly increased by
      failure to remove small inaccessible bone chips. The most formidable complication
      was CSF leakage which often resulted in infections of the central nervous system.

PMID- 18638742
TI  - Biomechanical evaluation of spinal stability after disc injury in a porcine
      model.
AB  - The biomechanical effects of disc injury on flexion-extension were investigated
      in nine fresh porcine functional spinal units. Under 12 N-m in extension and 6 N
      m in flexion, the range of motion among intact specimens were 23.11 degrees 
      33.29 degrees (mean = 26.07 degrees , SD = 3.25 degrees ), which shifted to 28.04
      degrees -38.46 degrees (mean = 31.69 degrees , SD = 3.50 degrees ) when discs
      were injured. Similarly, the neutral zones among intact and disc injured
      specimens were 4.88 degrees -12.75 degrees (mean = 9.32 degrees , SD = 2.60
      degrees ) and 9.50 degrees -24.43 degrees (mean = 16.80 degrees , SD = 4.69
      degrees ) respectively. To obviate the differences between tested specimens, the
      changes of neutral zone and the range of motion after disc injury were normalized
      and expressed as ratios as compared to the same items before disc injury. The
      neutral zone ratio ranged from 1.29 to 3.18 (mean = 1.87, SD = 0.55, p < 0.01).
      For range of motion, it ranged from 1.13 to 1.42 (mean = 1.22, SD = 0.09, p <
      0.01). The change of flexibility coefficient, however, was statistically
      insignificant in either flexion or extension. The model presented defines the
      range of motion, the neutral zone as well as the flexibility coefficient under a
      specific load. It suggests that major spinal instability can be elicited by a
      minimum flexion-extension moment, as reflected by a profound change of the
      neutral zone, after disc injury.

PMID- 18638743
TI  - Effect of nerve growth factor on delayed neuronal death and microtubule
      associated protein 2 after transient cerebral ischaemia in the rat.
AB  - The protective action of nerve growth factor (NGF) on delayed neuronal death
      (DND) after transient cerebral ischaemia and on the associated decrease in
      microtubule-associated protein 2 (MAP2) has been investigated. Transient
      forebrain ischaemia was induced for different periods (2 min, 5 min, and 8 min)
      in male Wistar rats by transient bilateral occlusion of the common carotid
      arteries and by lowering the systemic blood pressure to 50 mmHg. Histological
      evaluation of neuronal cell death and immunoblot analysis of MAP2 were made on
      the first and the seventh days after ischaemia. The mean cell death on the
      seventh day after ischaemia was 2.0%+/-1.8% in the 2-min group (n=6), 41%+/-19%
      in the 5-min group (n=6), and 75%+/-20% in the 8-min group (n=6). The
      concentration of MAP2 in the hippocampal homogenate 24 hours after ischaemia
      decreased to 82%+/-9% of the control value in the 2-min group (n=6), to 65%+/-8%
      in the 5-min group (n=6), and to 58%+/-4% in the 8-min group (n=6), and it
      remained constant at these levels through the seventh day after ischaemia. The
      protective action of NGF against DND was studied by administering 2 mug of 2.5S
      NGF (NGF-treated group, n=6) or artificial cerebrospinal fluid (CSF-treated
      group, n=6) through an osmotic pump implanted in the lateral ventricles 48 hours
      before the onset of ischaemia. The mean cell death on the seventh day after
      ischaemia was 42%+/-31% in the CSF-treated group, and 11%+/-15% in the NGF
      treated group. The concentration of MAP2 in the hippocampal homogenate on the
      first day after ischaemia was 75%+/-9% in the CSF-treated group, and 82%+/-6% in
      the NGF-treated group, and it remained at about the same levels up to the 7th day
      after ischaemia. These results suggest that, 1: degradation of MAP2 precedes DND,
      2: the severity of the preceding decrease of MAP2 correlated well with the
      severity of the DND, 3: intraventricular NGF has a protective effect against DND,
      and 4: the effect of NGF brain injury may be mediated by the modulation of MAP2
      metabolism.

PMID- 18638744
TI  - The diversity of presentation of herpes simplex encephalitis.
AB  - The case of a 63-year-old male who presented with what initially appeared to be a
      spinal or root lesion is presented. At autopsy a diagnosis of herpes simplex
      virus encephalitis was made. The diagnosis and pathology of this condition are
      discussed.

PMID- 18638745
TI  - Bilateral intracranial vertebral artery dissection associated with subarachnoid
      haemorrhage secondary to aneurysm formation.
AB  - We report the case of a 43-year-old woman who suffered repeated subarachnoid
      haemorrhages secondary to spontaneous intracranial vertebral artery dissection.
      The bleeding point was a saccular false aneurysm of the left vertebral artery.
      The saccular extension was located just distal to the origin of the posterior
      inferior cerebellar artery and was treated by clip occlusion of the neck. The
      case and condition are discussed.

PMID- 18638746
TI  - 1993 Vietnam-NSA conference on cranio-cerebral injuries.

PMID- 18638747
TI  - Tobacco mosaic virus replication in resistant and susceptible plants: in some
      resistant species virus is confined to a small number of initially infected
      cells.
AB  - Only small amounts of tobacco mosaic virus (TMV) are recoverable from directly
      inoculated leaves of some plant species, a phenomenon investigated by P. C. Cheo
      (1970, Phytopathology 60, 41-46) and termed subliminal infection. To interpret
      this phenomenon in two varieties of cowpea (Vigna sinensis Emil.), primary leaves
      were inoculated on their lower surfaces with TMV (common strain), and at various
      times postinoculation, mesophyll protoplasts were isolated, incubated for 36 hr,
      and stained with a TMV-specific fluorescent-labeled antibody. It was determined
      that only 1 in 50,000 to 150,000 protoplasts contained TMV antigen; this number
      remained essentially unchanged for experimental periods of from immediately after
      inoculation to up to 11 days postinoculation (the longest period examined).
      Cytological staining of epidermis from another subliminally infected host,
      cotton, also revealed infection of only a few cells. These data suggest that
      leaves of subliminally infected plants support TMV replication in those cells
      which receive virus during mechanical inoculation, but that the infectious
      principle is unable to move from those original centers in these hosts. Control
      experiments with tobacco (Nicotiana tabacum L. cv. Turkish Samsun), in which
      virus spreads extensively in the inoculated leaves, suggest that a rapid cell-to
      cell movement of the infectious entity begins after about 6 hr following
      inoculation. An unexpected observation was that some cowpea and tobacco mesophyll
      cells become infected immediately upon mechanical inoculation, suggesting that
      mesophyll cells can be primary sites of viral ingress into the leaf.

PMID- 18638748
TI  - Identification, cloning, and R-loop mapping of the polyhedrin gene from the
      multicapsid nuclear polyhedrosis virus of Orgyia pseudotsugata.
AB  - Polyadenylated RNA was isolated from Orgyia pseudotsugata larvae 8-10 days
      postinfection with the multicapsid nuclear polyhedrosis virus. This RNA was
      centrifuged through a sucrose gradient and fractions enriched for polyhedrin mRNA
      were identified by in vitro translation. Complementary DNA made to this RNA
      hybridized predominantly to a 5-kb fragment of XhoI-digested viral DNA. This
      fragment was cloned into the plasmid pACYC177 and mapped with restriction
      endonucleases. A SalI subclone with a 2.5-kb insert derived from the cloned XhoI
      fragment was found to select by hybridization only polyhedrin mRNA as determined
      by the size of the in vitro translation product and its precipitation by anti
      polyhedrin antibodies. The orientation of the polyhedrin gene and the region of
      the insert encoding the N terminus of the polyhedrin protein were determined by
      DNA sequencing. R-Loop mapping indicated polyhedrin mRNA is 980 +/- 75 bases long
      and contains about 250 nucleotides not represented in the final protein. The
      polyhedrin gene had no observable intervening sequences.

PMID- 18638749
TI  - The state of phage psi DNA in lysogenic cells of Agrobacterium tumefaciens.
AB  - Phage psi a temperate phage of Agrobacterium tunefaciens is mutagenic, grows
      poorly in strains which contain a pTi plasmid, and can be transferred by
      conjugation (D. Expert and J. Tourneur, 1982, J. Virol., 42, 283-291). In an
      attempt to explain these unusual properties we undertook a study of the state of
      psi DNA in the virion, during the lytic cycle, and in lysogenic cells. In the
      virions, the phage genome was found to consist of circularly permuted molecules.
      Covalently closed circular forms of these molecules could be detected in
      lytically infected cells. These appeared late in phage infection, accumulated in
      pTi-containing cells. The same circular forms were found in lysogens but they
      could not correspond to the permanent state of phage psi because they were
      present at less than one copy per cell. Restriction enzyme analysis and Southern
      blotting revealed the presence of a psi prophage integrated in the host
      chromosome. The site of integration in the chromosome was unique and the same in
      all lysogens tested. The results implied that the integration involves a circular
      form of psi DNA. The bearing of these findings regarding the properties of phage
      is discussed.

PMID- 18638750
TI  - Evidence for replication of cauliflower mosaic virus DNA in plant nuclei.
AB  - Cellular organelles of cauliflower mosaic virus-infected turnip plants were
      isolated, incubated with 32P-labeled deoxyribonucleoside triphosphates and
      assayed for their ability to synthesize virus-specific DNA. Only nuclei were
      found to synthesize a labeled DNA product. This DNA migrated during agarose gel
      electrophoresis at the same mobility as viral open circular DNA. When purified by
      excision and phenol extraction from agarose gels followed by digestion with EcoRI
      restriction endonuclease, the DNA gave the same array of digestion products as
      authentic viral DNA. These results suggest that CaMV DNA may replicate in plant
      nuclei.

PMID- 18638752
TI  - A system of neurotrauma care.

PMID- 18638751
TI  - The interaction of antibody with the major surface glycoprotein of vesicular
      stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal
      antibodies.
AB  - Monoclonal antibodies reactive with the major surface glycoprotein (G-protein) of
      vesicular stomatitis virus serotypes Indiana and New Jersey (VSV-Ind, VSV-NJ)
      have been isolated and characterized. The reactivity of each monoclonal was
      determined by enzyme-linked immunosorbent assay (ELISA), competitive binding
      assay (CBA), and the ability to neutralize infectivity. It was found that the
      majority of the antibodies were of the IgG(2a) subclass. In the CBA, unlabeled
      monoclonal antibodies were used to compete for radiolabeled antibodies in binding
      to solid-phase immunoadsorbents. The VSV-NJ G-protein appears to contain four
      nonoverlapping epitopes by these analyses. However, the VSV-Ind G-protein is more
      complex since four epitopes were defined which exhibited varying degrees of
      overlap. In some cases, this overlap was defined by complete reciprocal
      competition between antibodies with different reactivity patterns. In other
      instances, partial or nonreciprocal competition between antibodies was observed.
      These results may indicate epitopes in close proximity or suggest allosteric
      modifications in the G-protein induced by antibody binding. A fifth epitope on
      the Ind G-protein was defined by a monoclonal antibody which could bind to the G
      proteins of both VSV-Ind and VSV-NJ but could only neutralize infectivity of the
      VSV-Ind serotype.

PMID- 18638753
TI  - A review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage Part III:
      Mechanisms of action of calcium antagonists.
AB  - The possible mechanisms by which calcium antagonists are effective in the
      management of cerebral vasospasm are discussed. They number seven: relaxation of
      spastic arteries or prevention of spasm; opening up of collateral channels;
      neuronal protection at the membrane level; intracellular actions in neurones or
      vascular cells; alterations of blood rheology; antimitogenic effects; and
      improved fluid management of patients. A number of more minor actions may also be
      involved. It is likely that more than one mechanism is involved in their
      protective effect, especially at different periods in the time course of
      vasospasm.

PMID- 18638754
TI  - Under what circumstances can a doctor kill?

PMID- 18638755
TI  - Acromegaly: factors affecting the long term outcome after surgical treatment.
AB  - Survival and clinical status in 105 acromegalic patients followed for up to 24
      years after surgery is assessed against serum growth hormone (GH) levels and
      other factors. Primary treatment was at first (90)Yttrium implants or craniotomy,
      later transsphenoidal operation. GH levels were similar for each method, and the
      results were combined. Relief of presenting symptoms and tumour clearance related
      to early post-operative GH levels. Although the level at the last follow-up
      influenced clinical status at 10 years (P = 0.01), the major contributor was the
      age at diagnosis (P = 0.0002). Ten year survival was more likely when the final
      GH level was less than 5mug/l and at this level no tumour recurred. With GH less
      than 2 mug/l survival rate was higher and clinical status better. With GH between
      2 and 5 mug/l radiotherapy may be indicated; levels of Insulin-like Growth Factor
      I help in this decision. A plan of management is suggested.

PMID- 18638756
TI  - Human proprioceptive sensation.
AB  - What was the 'muscular sense' to Sherrington was later the 'joint sense', when it
      became the conventional wisdom that muscles are 'insentient'. These terms betray
      a view, still common in the field, that the basis of kinaesthetic sensibility
      must be either joint receptors or muscle receptors, but not both. However, the
      demonstrations that established that muscle receptors do have a role in
      kinaesthesia were not demonstrations that joint receptors play no part. Indeed,
      there have been specific demonstrations of kinaesthetic roles for joint
      receptors. It is clear that both muscle and joint receptors can be involved in
      giving specific kinaesthetic sensations, and that there is probably considerable
      redundancy between them. Furthermore, some cutaneous receptors give signals that
      could be the basis of quite good kinaesthetic performance, although there is not
      yet strong evidence of their being used for this. Apart from specific
      kinaesthetic roles for each receptor class, there is evidence of mutual
      facilitation between the submodalities. Sometimes this facilitation appears to be
      of a non-specific kind as seen for example in the dependence of kinaesthesia in
      the fingers upon cutaneous inputs.

PMID- 18638757
TI  - Epilepsy and primary cerebral tumours.
AB  - Although the association of epilepsy with cerebral tumours is well recognized,
      the reported incidence of seizures and relationship to tumour pathology varies
      significantly. This study assessed retrospectively the incidence of seizures,
      relationship to tumour pathology, natural history of epilepsy and prognostic
      significance of presentation with a seizure in 120 consecutive adults with
      histologically proven primary cerebral hemisphere tumours including meningiomas.
      52% had a seizure and most were at presentation. Seizures were more common with
      anaplastic astrocytoma (AA) (18 23 ) than glioblastoma multiforme (21 56 ) (p =
      0.001) and seizure occurrence was associated with cortical invasion. 52% of
      meningioma patients had a seizure. Seizures recurred in 34%, more frequently with
      glioma (19 of 46) than meningioma (1 of 15) (p < 0.05). Patients with AA
      presenting with a seizure had a longer survival (28 months) than patients without
      seizure (8 months) (p = 0.05 one sided). In conclusion, seizures are a common
      complication of cerebral tumours, usually at presentation and correlate with
      tumour pathology. A seizure at presentation in AA correlates with longer
      survival.

PMID- 18638758
TI  - Carotid body tumour: microvascular Doppler flowmeter for shunt placement.
AB  - During the span of five years from October, 1987 to December, 1992, we have
      operated on six cases of carotid body tumours. Total excision was performed in
      five patients; one patient had 90% of the tumour excised. All patients had pre
      operative balloon occlusion test; only one patient showed electroencephalographic
      changes. Three patients required intra-operative intraluminal shunts for various
      reasons. Microvascular Doppler flowmetery confirmed patency and correct placement
      of the shunt. Elective use of the intraluminal shunt is very useful for safe
      excision of carotid body tumours. Microneurosurgical techniques were used for all
      patients. There were no cerebrovascular sequelae and 25% of patients experienced
      cranial nerve injury. Average follow up was three years and none of the total
      excision patients have had recurrence of the tumours.

PMID- 18638759
TI  - Air rifle injury to the head.
AB  - The authors reviewed 16 cases of air rifle injuries to the head, 14 of them were
      penetrating. While 50% of the victims were adults, almost all of the culprits
      were children. The entry wounds were mostly in the frontal area and around or
      exactly on the eye. None was perforating or through and through. The morbidities
      encountered were considered to be severe in 2 cases (hemiparesis), ocular
      injuries in 3 cases, and visual field defects in 3 cases. 1 patient died due to
      recurrent haemorrhage. The initial wound debridement and short course of
      antibiotic perioperatively seemed to be most important. Retained pellets were
      removed only if they were accessible. Considering the risk of morbidity and
      mortality and the fact that almost all of the culprits were children, air rifles
      should require adequate precautions and especially be kept out of the reach of
      children.

PMID- 18638760
TI  - The haemodynamic consequences of a carotid-jugular fistula in the rat during
      hypocapnia.
AB  - This study was undertaken to examine further the effects of hypocapnia and the
      contribution of hypotension to the haemodynamic consequences of cerebral
      arteriovenous fistula ablation in the rat chronic carotid-jugular fistula model.
      Regional cerebral blood flow (rCBF) was measured by the (14)C-iodoantipyrine
      technique under halothane anaesthesia 12 weeks after the creation of the fistula.
      rCBFs in all groups were conducted at a similar PaCO(2) (22-26 mmHg). The rCBF in
      control animals ranged from a mean of 51-71 ml/100 g/min at a mean systemic
      arterial pressure of 136 mmHg, and 56-71 ml/100 g/min at a mean systemic arterial
      pressure of 89 mmHg after 2.5 ml blood loss. These values correspond to those
      expected for this degree of hypocapnia in rats without a carotid-jugular fistula.
      In animals with an open carotid-jugular fistula created 12 weeks prior to the
      study, mean rCBFs at comparable blood pressure ranged from 23-33 ml/100 g/min in
      normotensive animals and 29-44 ml/100 g/min in the hypotensive animals. These
      flows were not significantly different. The conclusion of this study is that the
      carotid-jugular fistula group is able to autoregulate and maintain a constant
      regional cerebral blood flow during the challenge of hypotension under hypocapnic
      conditions. This ability to autoregulate is preserved despite the chronic
      hypoperfusion due to the arteriovenous shunt and the added insult of low regional
      cerebral blood flows caused by hypocapnia at the time of the experiment.

PMID- 18638761
TI  - Interleukin regulation of prolactin and corticotropin from pituitary adenoma.
AB  - Recent findings indicate that lymphokines, leukocyte-derived hormones, interact
      with the hypothalamic-pituitary axis. We examined the role of neurotrophic
      lymphokines in the neuroendocrine system. Specifically, the action of Interleukin
      (IL)-1b, IL-2 and IL-6 upon the anterior pituitary hormones, growth hormone (GH),
      prolactin (PRL) and adrenocoticotropic hormone (ACTH) were studied in rodent
      pituitary adenoma cell lines. Hormone release by GH and PRL-producing rat adenoma
      cells (GH3) and ACTH-producing mouse adenoma cells (AtT-20) was analyzed by
      radioimmunoassay (RIA). Recombinant (r) IL-1beta decreased PRL release from GH3
      in a dose-dependent fashion. IL-1 inhibition of PRL production occurred in
      parallel with IL-1 inhibition of DNA synthesis in GH3 as measured by [(3)H]
      thymidine incorporation. This result strongly indicates that IL-1 alters PRL
      production by adenoma cells at the translational level. Low dose IL-2 (10 U/ml)
      enhanced ACTH production from AtT-20, but higher concentrations of IL-2 failed to
      affect the release of ACTH. IL-2 did not change the incorporation of [(3)H]
      thymidine in AtT-20. Previous studies showed that IL-1 and IL-6 induce a
      significant secretion of ACTH via the hypothalamic-pituitary axis. However, IL-1
      and IL-6 failed to affect ACTH secretion by AtT-20. Blood-derived cytokines have
      direct effects on hormone secretion by pituitary adenoma cells in vitro.

PMID- 18638762
TI  - Hydrocephalus in pfeiffer syndrome.
AB  - A review of the clinical records and CT scan findings of 11 patients with
      Pfeiffer syndrome showed ventricular dilation in the majority. In 7 cases the
      ventriculomegaly was sufficiently severe as to be classified as hydrocephalus and
      warrant ventricular shunting. The common co-existence of hydrocephalus and
      multiple premature sutural fusion in Pfeiffer syndrome is a further factor in the
      apparently worse prognosis of this condition when compared to Crouzon and Apert
      syndrome. Primary cerebral anomalies as a causative factor for the development of
      hydrocephalus are infrequently recorded. Extensive craniosynostosis with cranial
      base distortion and constriction would appear to contribute to the production of
      hydrocephalus.

PMID- 18638763
TI  - Aplasia of the posterior arch of the atlas.
AB  - A case of aplasia of the posterior arch of the atlas with persistence of the
      posterior tubercle in a 14-year-old youth is presented. The pathogenesis and
      clinical implications of the condition are discussed.

PMID- 18638764
TI  - Multimeric forms of satellite of tobacco ringspot virus RNA.
AB  - An approximately 350-nucleotide residue RNA replicates in association with
      tobacco ringspot virus (TobRV) and becomes encapsidated in TobRV coat protein.
      Here we show by electrophoretic analyses that this small satellite RNA, RNA S, is
      the most abundant and most rapidly migrating of a series of at least ten
      encapsidated RNAs with RNA S sequences. A largely double-stranded RNA fraction
      from infected tissue, when denatured, gave a similar series of up to 12 zones
      that contained both RNA S sequences and sequences that hybridized to RNA S.
      Analysis of the mobilities suggests a weight increment between each zone
      corresponding approximately to the size of RNA S. Thus the more slowly migrating
      zones appear to contain covalent multimers of RNA S or, for tissue RNA, both
      multimers of RNA S and multimers of the complement of RNA S sequences. Neither
      terminal structure of TobRV genomic RNAs was found in the satellite RNA. RNA S
      lacks detectable polyadenylate or oligoadenylate. Covalently linked protein was
      not detected in RNA S or its more slowly migrating forms, and satellite RNA
      biological activity, unlike that of the TobRV RNAs, was not protease sensitive.
      Polynucleotide kinase catalyzed the phosphorylation of satellite RNAs, indicating
      free 5'-hydroxyl groups.

PMID- 18638765
TI  - Editorial.

PMID- 18638766
TI  - Anterior circulation aneurysms: surgical perspectives.
AB  - Aneurysms arising from the internal carotid circulation represent 85% of all
      intracranial aneurysms. The intimate relationship of the internal carotid artery
      and its branches with the brain and cranial nerves, and the distribution of the
      internal carotid artery flow, make these aneurysms challenging, and potentially
      complicated in their surgical management. Great attention to detail, and clear
      understanding of the operative anatomy of the carotid system, facilitate the safe
      and successful treatment of these aneurysms. The surgical experience with 475
      anterior circulation aneurysms treated from 1980 to 1992 is presented. The
      aneurysms arose from the internal carotid artery: 230(40%), middle cerebral
      artery: 152(32%), and anterior cerebral artery: 133(28%). Of aneurysms arising
      from the internal carotid artery, there were 142(30%) from the posterior
      communicating artery; internal carotid bifurcation: 29(6%), and anterior
      choroidal artery: 19(4%). There were 62(13%) giant aneurysms evenly distributed
      among the middle cerebral, internal carotid bifurcation and anterior cerebral
      artery. Serious neurological morbidity was observed in 13(3%) patients, who
      presented a combination of different neurological symptoms including: hemiplegia
      3, hemiparesis 6, dysphasia 7, and loss of vision 4. Two patients developed a
      myocardial infarct and survived. Mortality occurred in 16(3%); these patients
      died from: a hemispheric infarction 7, severe vasospasm 6, myocardial infarction
      2, and pulmonary emboli 1. All aneurysms appeared angiographically obliterated.
      Vasospasm was observed in 75(16%) patients of which nine were symptomatic, and
      six of them died. Six major arterial trunks were occluded in the post-operative
      angiogram, and three patients had occlusion of the internal carotid artery, not
      identified during surgery. Three of these patients with unexpected occlusions
      died from a major cerebral infarction, and three had lasting hemipareses and
      dysphasia. Surgical correction of internal carotid aneurysms can be conducted
      safely when the anatomical characteristics of the intracranial vessels is
      preserved, and when these patients are treated with appropriate medical support.

PMID- 18638767
TI  - Human neural transplantation.
AB  - Great advances in neurobiology have resulted from 100 years of neural
      transplantation research. In the last 20 years, there has been a focus on using
      neural transplantation to repair the damaged central nervous system (CNS)
      utilising experimental animal models of various human neurodegenerative disease
      and CNS injury. Since 1985, there has been a rapid proliferation of adrenal
      medullary autograft transplantation to the caudate nucleus of humans with
      Parkinson's disease. However, this operation proved to be unsuccessful and was
      associated with unacceptable morbidity. Implantation of human fetal mesencephalon
      into patients with severe parkinsonism has supplanted the adrenal operation and
      has produced promising results, with some patients reported to improve markedly
      and some evidence of graft survival noted on positron emission tomography (PET).
      Host tissue recovery appears to be an important mechanism for this clinical
      improvement. The optimal technique is to use three to four fetuses from induced
      abortions of 6.5 to 8 weeks gestation, with multiple stereotactic implants into
      the putamen and caudate nucleus. Many biological questions still remain and the
      community remains troubled by the ethical problems of using fetal tissue obtained
      from abortions. This procedure is still experimental and should be restricted to
      a few centres with excellence in cell and molecular biology. A multicentre study
      is needed to more carefully evaluate CNS transplantation. Cloned neural precursor
      cells or immortalized embryonic cell lines genetically modified to manufacture
      selected growth factors or neurotransmitters may offer an alternative to the use
      of human fetal tissue. Much more experimental animal research is necessary before
      transplantation can be used to treat other CNS maladies.

PMID- 18638768
TI  - Early surgery for posterior circulation aneurysms following subarachnoid
      haemorrhage.
AB  - A retrospective analysis of 32 patients with posterior circulation aneurysms
      operated on within three days of subarachnoid haemorrhage is presented. The cases
      were treated at two Australian neurosurgery units over a five year period (1988
      1992), both units having a policy of treating patients of all grades and all ages
      with early surgery. No patients suffered rebleeding. Five patients developed
      clinical vasopasm. Twenty-four patients (75%) had a good outcome (Glasgow Outcome
      Score 1-2), three had a poor outcome (GOS 3), and five died (16%). Of the five
      deaths, three presented as Hunt and Hess grade V. The results are considered in
      detail and the literature regarding the timing of surgery for posterior
      circulation aneurysms is reviewed.

PMID- 18638769
TI  - Surgical management of comatose patients with cerebellar infarction.
AB  - A series of 20 patients with cerebellar infarction were classified into four
      groups based on the clinical and CT findings. Two comatose patients who developed
      acute hydrocephalus (Group 2) are presented and were successfully treated with
      external ventricular drainage (EVD) alone. Continuous post-operative monitoring
      of intracranial pressure (ICP) demonstrated that EVD had sufficiently controlled
      ICP and therefore suboccipital decompression of the cerebellum was not indicated
      even though the patients were not immediately responsive to EVD. Both patients
      made a gradual recovery: a 57-year-old woman, independently ambulatory, was
      discharged to her home and a 76-year-old woman, ambulatory with assistance, was
      discharged to a rehabilitation hospital. The results of our two cases suggest
      that EVD should be the first treatment in cases of cerebellar infarction with
      cerebellar swelling or oedema accompanied by hydrocephalus. Posterior fossa
      decompression and removal of infarcted cerebellar tissue should be indicated only
      in cases where ICP can not be controlled by EVD, even if there is no immediate
      recovery of the patient's impaired consciousness. Reviewing the literature
      pertinent to our two cases, the use of ventricular drainage alone in the
      management of cerebellar infarction with ischaemic cerebellar swelling is
      discussed.

PMID- 18638770
TI  - Frameless stereotaxis for the insertion of lumbar pedicle screws.
AB  - Spinal instrumentation and frameless stereotaxy are two separate fields in
      neurosurgery that have rapidly advanced in recent years. The application of
      stereotaxis to spinal surgery has previously been limited by the inaccuracy of
      surface mounted reference points. The development of frameless stereotaxy using
      anatomical registration techniques has overcome this problem and has allowed
      stereotactic techniques to be successfully applied to spinal surgery at our
      institution. We tested our frameless spinal stereotactic technique in cadaver
      studies with optimal screw placement. The technique is currently undergoing
      preliminary clinical evaluation. We review the technique and its application to
      spinal instrumentation.

PMID- 18638771
TI  - Targeting therapy for glioma by LAK cells coupled with bispecific antibodies.
AB  - Targeting of T cells or natural killer (NK) cells to tumours by using bispecific
      antibodies has attracted increasing interest in the past few years. We treated 31
      patients with malignant glioma using adoptive transfer of lymphokine-activated
      killer (LAK) cells coupled to a bispecific antibody (anti-CD3+anti-glioma) as
      post-operative adjuvant therapy. Although this study excluded patients with
      deeply-seated tumours or a poor performance status, approximately 50% of the
      patients remained alive after 3 years, and 40% were free of recurrence. Serial CT
      scans revealed disappearance of remnant tumours in some patients. In addition, CT
      guided stereotactic biopsy of the tumour in 3 patients showed extensive necrosis
      and degeneration after specific targeting therapy (STT). Five patients developed
      acute infection, and one of them died of bacterial meningitis. Our results
      suggest that antibody-targeted LAK therapy can achieve a higher response rate in
      patients with standard LAK therapy or any type of conventional treatment.

PMID- 18638772
TI  - Experimentally induced cerebral aneurysms as model for non-surgical treatment.
AB  - This article summarizes the results of our experimental studies on the
      pathogenesis of cerebral aneurysm. Experimentally induced aneurysms in rats and
      in monkeys resemble those of human cases both in location and in microscopic
      structure. By studying early changes of aneurysm development, it is proposed that
      degenerative changes in the intima caused by haemodynamic stress at vessel
      branches are the basis for aneurysm formation and aneurysms develop, at least
      partly, because of defective or decreased healing processes there. By giving the
      experimental animals blood coagulation factor XIII, which is known to enhance
      wound healing, a significant amount of intimal proliferation occurred in and
      around aneurysms. Some aneurysms were completely obliterated. This fact may
      indicate a possibility of non-surgical treatment of the disease in the future.
      Suggestive findings in human autopsy cases are also presented.

PMID- 18638773
TI  - Lhermitte-Duclos disease.
AB  - Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) is a rare
      pseudo-neoplastic disorder of the cerebellum with typical MRI findings. A 25-year
      old man presenting with progressive neck pain, dizziness, and impaired vision is
      reported. CT and MRI revealed a left cerebellar haemispheric mass and obstructive
      hydrocephalus. Lhermitte-Duclos disease was histologically confirmed after
      surgical removal of the lesion. The typical MRI appearance of a nonenhancing
      haemispheric cerebellar mass with preservation and exaggeration of the normal
      gyral pattern allows pre-operative diagnosis of this condition. The literature is
      reviewed and clinical presentation, radiology and histopathology are discussed.

PMID- 18638774
TI  - Remission of essential hypertension following decompression of a giant aneurysm
      of the right vertebral artery.
AB  - We report a case with giant aneurysm of the right vertebral artery in which
      remission of essential hypertension occurred following surgical decompression.
      The patient presented with a history of progressive gait disturbance and
      essential hypertension over a period of 4 years and 10 years respectively.
      Computerised tomography scan demonstrated a giant thrombosed aneurysm in the
      right vertebral artery. The aneurysm was trapped and decompressed to reduce the
      neurological deficits. Post-operatively, the gait disturbance recovered with
      complete remission of the long standing essential hypertension.

PMID- 18638775
TI  - Neurosurgery in the pre-European era in Australia.
AB  - Trephination was widely recognised as an achievement of many primitive cultures
      but until Dr Stephen Webb identified two Australian Aboriginal skulls it was not
      believed to have occurred on the continent of Australia. The technique and actual
      instruments used in New Britain for trephination are examined and the two skulls
      discovered by Dr Webb are presented.

PMID- 18638776
TI  - The clinical neurosciences.

PMID- 18638777
TI  - Tissue rescue therapy for acute ischaemic stroke.
AB  - Despite population-based declines in stroke mortality, the individual mortality
      rate in ischaemic stroke approaches 20%, with substantial morbidity in the
      majority of survivors. Reduction of this rate will depend on the advent of
      effective acute tissue rescue therapy. Based on improved understanding of the
      pathophysiology of acute ischaemia, it is now recognised that the time window for
      therapeutic intervention is only a few hours after stroke onset. The major
      therapeutic strategies currently being investigated include firstly approaches to
      improve reperfusion after ischaemia, such as thrombolysis, haemorheological and
      antithrombotic therapies, and secondly strategies for neuronal protection such as
      calcium channel and NMDA antagonists and free radical inhibitors. Based on
      promising animal and early human studies, the results of large randomised,
      placebo-controlled clinical trials are expected in the near future and should
      have a profound effect on acute stroke management.

PMID- 18638778
TI  - Retroviruses and DNA: gene therapy for brain tumours.
AB  - Gene therapy is a revolutionary new approach to the treatment of cancer, with
      potential use as an adjuvant and possibly even primary therapy for malignant
      brain tumours. Retroviral vector mediated transfer is the first mechanism for the
      introduction of foreign genes into target cells that is efficient, selective and
      safe enough to warrant the development of clinical therapeutic protocols in
      humans. Expression of the transduced herpes simplex thymidine kinase gene in
      glioma cells renders them highly sensitive to the toxic effects of ganciclovir.
      This gene has been transduced into central nervous system (CNS) tumours in vivo
      resulting in significant tumour cell death and in some cases, complete tumour
      eradication. Formidable technical obstacles still remain to be overcome before
      gene therapy can be generally accepted as a treatment modality. If the
      development of gene therapy on both a technological and commercial level
      continues at the current exponential rate then it is surely only a matter of time
      before these hurdles are overcome.

PMID- 18638779
TI  - Endovascular treatment of intracranial aneurysms.

PMID- 18638780
TI  - The Guglielmi coil for transarterial occlusion of intracranial aneurysm:
      preliminary Western Australian experience.
AB  - 18 patients aged 3-75 years with cranial arterial aneuryms have been treated by
      transarterial insertion of Guglielmi Detachable Coils (GDC). 11 patients had
      previously bled and 9 pts had previous craniotomy for the same aneurysm. 22
      technically successful procedures were performed in 17 aneurysms (16 patients).
      Subsequent repacking was performed 8 times (5 patients). There were 4
      unsuccessful procedures in 2 patients. Including repackings, 9 aneurysms (8
      patients) show complete occlusion and 7 aneurysms are considered stable with
      either a neck remnant or persistent partial filling of the aneurysm. 1 aneurysm
      showed repeated recanalisation necessitating multiple repackings. 1 patient
      developed recanalisation, aneurysm enlargement and died of recurrent subarachnoid
      haemorrhage (SAH) at 7 months. 8 patients suffered procedural complications or
      deficits. 3 patients showed occlusion of a parent artery. On 6-18 month follow up
      13 survivors are well and symptom free and 1 has recovered mild hemiparesis.
      Three recent patients are progressing well but await follow up. Our results are
      compared with a larger series reported from the North American GDC trial.

PMID- 18638781
TI  - Unilateral motor epileptic seizures.
AB  - Unilateral motor epileptic seizures occurred in 118 of 1902 persons with seizure
      disorders referred to a consultant neurological practice over a 30 year period.
      The unilateral motor seizures were nearly always manifestations of partial
      (focal, localisation related) epilepsy but, particularly if they occurred on
      different sides on different occasions, could be due to generalised onset
      epilepsy (10.2% of cases). The risk of cerebral tumour in those with unilateral
      motor seizures (10.2%) was greater than that for those with all other forms of
      seizure disorder (relative risk 3.56 times; 95% C.I. = 1.95 to 6.49 times).
      Unlike the situation in younger persons, if unilateral motor seizures began after
      the age of 20 years the chance of an underlying cerebral tumour (23.4%) was
      significantly higher than in other persons with adult onset partial seizures
      (relative risk 2.62 times; 95% C.I. = 1.44 to 4.77 times) and was much greater
      than that in all other seizure sufferers (relative risk 8.35 times; 95% C.I. =
      4.66 to 14.9 times).

PMID- 18638782
TI  - Stereotactic biopsy of cerebral lesions in acquired immunodeficiency syndrome.
AB  - The efficacy, mortality and morbidity of CT directed stereotactic biopsy of a
      cerebral lesion in 32 Human Immunodeficiency Virus (HIV) infected patients
      between July 1991 and June 1994 who had an atypical presentation for
      toxoplasmosis or who were failing or intolerant of empirical antitoxoplasmosis
      treatment was evaluated. An histological diagnosis was able to be made in 85%:
      progressive multifocal leucoencephalopathy (PML) in 13, primary cerebral lymphoma
      in 10, toxoplasmosis in 3 and HIV encephalitis in one. Non-specific reactive
      changes or gliosis were seen in 5 patients. There was no mortality, and morbidity
      occurred in 2 patients: one intraventricular haemorrhage and one transient third
      nerve palsy. Correct diagnosis made by image-directed stereotactic biopsy of
      central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS)
      patients may improve outcome, particularly in those diseases where effective
      treatment strategies already exist and become increasingly available in the
      future.

PMID- 18638783
TI  - Intracranial abnormalities and ventricular patterns associated with
      meningoencephaloceles.
AB  - Twenty-eight patients with meningoencephalocoeles with a mean age of 11 months
      were studied. CT scans showed abnormal ventricular patterns and other
      intracranial abnormalities in 78%, about 2 3 of whom had multiple defects. There
      was a direct relationship between the number of intracranial abnormalities and
      the amount of herniated brain and not with the size of the meningocele sac per
      se. We believe that traction on the intracranial contents by progressive brain
      herniation is a primary mechanism leading to the development of multiple
      abnormalities. It is therefore recommended that early closure of the bone and
      dural defects is necessary to prevent further brain herniation. We have utilized
      multiple stage operations including cerebrospinal fluid shunting for
      hydrocephalus, when present, transcranial extradural closure of the bone and
      dural defects, and cosmetic repair of the mengingocoele sac at a much later date.

PMID- 18638784
TI  - The long duration response to levodopa in Parkinson's disease.
AB  - The duration of effect of levodopa has been reported by some authors to be
      shorter in fluctuating parkinsonian patients with long standing disease than in
      stable patients. Other authors report no difference in the two groups of
      patients. We assessed motor fluctuations and response duration in 15 Parkinson's
      disease patients. Three patterns of response were observed: deterioration within
      one day on placebo and marked fluctuations on levodopa; deterioration after one
      day on placebo and moderate fluctuations on levodopa; no deterioration during 3
      days of placebo and no fluctuations on levodopa. One patient who did not
      deteriorate or fluctuate did both when restudied 12 years later. This study
      confirms that, in addition to the short duration response to a single dose of
      levodopa, there is a long duration response to levodopa which is lost as the
      disease progresses. Loss of this long duration response to levodopa may be a key
      factor in the emergence of fluctuations in Parkinson's disease.

PMID- 18638785
TI  - Traumatic basal ganglia haemorrhage: report of 7 cases.
AB  - We report 7 cases of traumatic basal ganglia haemorrhage (TBGH), which is closely
      related to diffuse axonal injury (DAI). Although most of our patients were in
      coma for more than 24 hours, the outcome was relatively favourable. All the
      patients regained consciousness, and 2 of 4 patients with contralateral
      hemiparesis showed improvement. Although expressive and nonfluent aphasia
      occurred in 5 patients, all of them recovered completely. The outcome in TBGH may
      be better than previously believed.

PMID- 18638786
TI  - Diagnostic markers demonstrating successful culture of human meningioma cells.
AB  - The light microscopic and ultrastructural features of cultured meningioma cells
      were compared with those of surgically resected specimens. Meningioma cells
      normally show variable degrees of epithelial or mesenchymal differentiation. In
      cultured cells, well formed psammoma bodies and whorls were seen by light
      microscopy and specialised intercellular junctions were observed by electron
      microscopy. Cytogenetic analysis was also shown to be a useful diagnostic marker
      to differentiate cultured meningioma from contaminant proliferating fibroblastic
      and endothelial cells. These methods have demonstrated that the cells cultured
      from operative samples were predominantly meningioma cells. The ability to
      reproducibly cultivate populations of meningioma cells should facilitate in vitro
      assessment of potential adjunctive treatment modalities.

PMID- 18638787
TI  - Phthalocyanine photosensitizers for the treatment of brain tumours.
AB  - In vitro and in vivo studies were undertaken utilizing an established rat glioma
      cell line (C6) to compare the phototoxicity characteristics of aluminium
      tetrasulfonated phthalocyanine (AlSPc), zinc tetrasulfonated phthalocyanine
      (ZnSPc) and haematoporphyrin derivative (HpD). AlSPc and ZnSPc were inherently
      less cytotoxic in the dark compared to HpD with 50% colony survival at 275, 355
      and 14 mug/ml respectively. An in vitro phototoxicity study at equimolar
      concentrations demonstrated a 50% reduction of colony survival after exposure to
      white light at 1 minute for HpD, 10 minutes for AlSPc and 12 minutes for ZnSPc.
      The presence of fetal bovine serum (FBS) in the medium resulted in reduced in
      vitro uptake of AlSPc and increased cellular retention which was determined
      quantitatively by a fluorescence assay following extraction. This assay was also
      used to determine the in vivo uptake of AlSPc, which was maximal in the
      intracerebral C6 glioma model at 6 hours (12.3 mug/g tissue) post-intravenous
      administration of a 1 mg/kg dose of AlSPc, corresponding to a tumour: normal
      brain ratio of 22:1.

PMID- 18638788
TI  - Multiple germinomas due to early intracranial metastasis.
AB  - A case with multiple intracranial germinomas involving basal ganglia and corpus
      callosum is presented. Clinical and sequential neuroradiological studies
      demonstrated the entire course of multiple tumour development. These findings
      suggested that the multiple tumours were intracranial metastatic deposits from
      primary germinoma in the pineal body. A common primary pineal or suprasellar
      lesion should be carefully ruled out in the cases of germ cell tumours occurring
      in unusual regions.

PMID- 18638789
TI  - Aneurysmal haemorrhage in a 6-month-old male.
AB  - This case illustrates the typical features of saccular aneurysms occurring in
      children under the age of 5 years. The child was male and presented with a
      subarachnoid/intracerebral haemorrhage secondary to a large ruptured saccular
      aneurysm of the distal middle cerebral artery. Surgical management was undertaken
      and despite an initial poor clinical grade, the baby has enjoyed an excellent
      clinical outcome. The clinical features of the case, histology of the aneurysm
      and review of the literature are presented.

PMID- 18638790
TI  - Dissecting aneurysm of the extracranial vertebral artery after endovascular
      surgery.
AB  - A 43-year-old man with a scalp arteriovenous fistula developed cerebellar and
      pontine infarctions after an endovascular procedure. Nine months after the
      procedure, the patient experienced transient loss of consciousness. A fusiform
      dilatation of the left vertebral artery at the level of the atlas was found on
      angiography. The lesion was excised and a saphenous vein graft was interposed.
      Histological examination of the resected specimen revealed a dissecting aneurysm.
      This may have been precipitated by subintimal passage of the guide wire/catheter
      at the time of his endovascular surgery or by chemical damage to the arterial
      wall from embolic material.

PMID- 18638791
TI  - Cucumber mosaic virus-associated RNA 5. IX. The overtaking of viral RNA synthesis
      by CARNA 5 and dsCARNA 5 in tobacco.
AB  - Cucumber mosaic virus (CMV) and CMV-associated RNA 5 (CARNA 5)-related RNA
      synthesis was monitored under conditions of semisynchronous infection using a
      differential temperature inoculation technique (Dawson and Schlegel, 1973). Leaf
      strips sampled at specific intervals between 0 and 100 hr after temperature shift
      were vacuum infiltrated with [32P]phosphoric acid and actinomycin D and incubated
      during 4-hr periods. Total nucleic acid extracts were analyzed on polyacrylamide
      gels to compare the relative rates of 32P incorporation into CMV-RNA 3, CARNA 5,
      and dsCARNA 5. During the first 24 hr there was a rapid increase in the rate of
      32P incorporation into all three RNAs. During the next 10-20 hr the rate of 32P
      incorporation into RNA 3 declined to minimal levels while that of CARNA 5 stayed
      at a plateau or declined slowly. In contrast, the rate of 32P incorporation into
      dsCARNA 5 increased steadily well beyond the first 48 hr after temperature shift.
      The distribution of radioactivity among its (+) and (-) strands was determined by
      isolating the dsCARNA 5 in each nucleic acid extract obtained from the 4hr
      labeled tissues and determining its radioactivity after hybridization in the
      presence and in the absence of a large excess of unlabeled CARNA 5. It appeared
      that throughout the 100-hr experiment about 60% of the radioactivity of dsCARNA 5
      was in its (+) strands. The rates of 32P incorporation into virus and CARNA 5
      related RNAs were also compared in leaf strips from plants inoculated with the
      genomic CMV-RNAs alone and with a mixture of genomic RNAs and CARNA 5. Although
      in the infection with the genomic RNAs alone the synthesis of CARNA 5 and dsCARNA
      5 was not prevented, the increase in their relative rates of synthesis seemed
      significantly slower and the relative rate of RNA 3 synthesis much greater than
      when the inoculum contained detectable CARNA 5.

PMID- 18638792
TI  - Systemic acquired resistance induced in hypersensitive plants by nonnecrotic
      localized viral infections.
AB  - Localized symptomless infections of cucumber cotyledons and first foliage leaves
      by tobacco mosaic virus (TMV) induced systemic acquired resistance in other
      leaves of the same plants inoculated 2 weeks later with tobacco necrosis virus.
      Diameters of lesions that developed after the second inoculation were 35% less
      and lesion numbers were 30% fewer than in control plants not previously
      inoculated with TMV. Thus, necrosis after the first inoculation was not
      prerequisite to virus-induced systemic acquired resistance.

PMID- 18638793
TI  - Migraine: a continuing problem.

PMID- 18638794
TI  - Impact of the 25th chromosome on mitochondrial dysfunction in human disease.
AB  - Human mitochondrial DNA, the 25th chromosome, is a 16 569 base pair long circular
      molecule, that encoders a variety of genes for the translational machinery of the
      mitochondrion, as well as 13 structural proteins, that are all subunits of the
      respiratory chain (RC). A variety of alterations of mitochondrial DNA (mtDNA) are
      now functionally and genetically linked to human disease, including
      encephalomyopathies, Leber's hereditary optic neuropathy, diabetes mellitus, some
      neurogenerative diseases and even ageing. The mitochondrial encephalomyopathies
      are a clinically, biochemically and genetically heterogeneous group of disorders.
      Alterations of mtDNA include point mutations, encephalomyopathies, as well as in
      the other human diseases, are reviewd.

PMID- 18638796
TI  - Neural grafting: today, tomorrow-or never?

PMID- 18638795
TI  - Neurosurgery in papua new Guinea.

PMID- 18638797
TI  - Posterior lumbar interbody fusion using the Ray threaded fusion cage.
AB  - Though recommended some years ago by Cloward, PLIF (posterior lumbar interbody
      fusion) was not widely used for many years. Recently many authors have recognised
      PLIF as a preferred technique for lumbar stabilisation. Preservation or re
      establishment of disc height is associated with an improved patency of the
      intervertebral foramen. The use of the threaded fusion cage (TFC) provides
      immediate stabilisation, preservation of disc height due to highly resistant
      material, and long term fusion with autogenous bone. The instrumentation,
      designed in association with the cage, provides a safe environment for the neural
      structures during the procedure. It also makes the procedure more reproducible
      and less dependent on the operator. The learning curve for doing the operation is
      rapid. Using the Prolo scale, on the economic and functional scales, 83% of cases
      were rated good to excellent. The fusion rate was 94% at one year.

PMID- 18638798
TI  - Treatment of hemifacial spasm with botulinum toxin.
AB  - Botulinum toxin (BT) injections were used over a two year period to treat 66
      patients with disabling hemifacial spasm (HFS). Good to excellent results were
      obtained in 89.2% of patients for a mean period of 18 weeks. Temporary side
      effects occurred in about 20% of individuals EMG guidance was of assistance in
      injecting the lower half of the face. MRI imaging was far superior to CT scanning
      in the investigation of HFS.

PMID- 18638799
TI  - Cerebellar medulloblastomas: a comparison between adults and children.
AB  - A retrospective analysis of 19 medulloblastomas in patients aged 2 to 24 years
      was conducted employing 14 children (<15 years old) and 5 adults. All patients
      received gross total excision of the tumour with postoperative craniospinal
      irradiation. The patients were then followed up for more than 5 years. To
      determine which factors influenced the prognosis of these two age groups, we
      analysed the differences of the proliferating cell nuclear antigen (PCNA), the
      degree of tumour invasion and the outcome between adult and childhood
      medulloblastomas. In summary, medulloblastomas in adults and children had similar
      cell proliferative activity and long term survival rates but the tumours with
      brain stem invasion, which commonly occurred in children, had an early recurrence
      rate and a poor prognosis. The prognosis of medulloblastoma may depend upon the
      degree of tumour invasion of the brain stem.

PMID- 18638800
TI  - Postero-ventral pallidotomy in Parkinson's disease.
AB  - Fetal graft research and renewed interest in Leksell's postero-ventral
      pallidotomy (PVP) stimulated reconsideration of surgical therapy for Parkinson's
      disease (PD), particularly with regard to improving akinetic symptoms previously
      thought resistant to surgical lesions. A review of our series and other published
      results of PVP and fetal grafts, show that PVP has beneficial effects on both
      akinetic and hyperkinetic symptoms that exceed the results reported for fetal
      graft implantation and other conventional stereotactics. Using the Unified
      Parkinson's Disease Rating Scale (UPDRS) for pre- and postoperative evaluation of
      113 P-V pallidotomies, we found that PVP gave significant reductions in total
      UPDRS scores, as well as hyperkinetic and akinetic motor scores, dyskinesias, and
      'off' periods (P</=0.01). Moreover, P-V pallidotomy's dramatic therapeutic
      effects on akinesia may be explained by interruption of amplified collateral
      inhibitory output from the pallidum to brain stem locomotor centers such as the
      pedunculopontine nucleus, whereas interruption of collaterals to ventral lateral
      thalamus by PVP may account for the elimination of hyperkinesia. The excellent
      results of PVP represent a significant advance in the surgical treatment of
      Parkinson's disease.

PMID- 18638801
TI  - Aluminium phthalocyanine mediated photodynamic therapy in experimental malignant
      glioma.
AB  - The efficacy of aluminium tetrasulfonated phthalocyanine (AISPc) as a
      photosensitizer for photodynamic therapy (PDT) was investigated in the C6 glioma
      model in Wistar rats. The depth and extent of tumour necrosis was dependent on
      both the dosage of intravenously (IV) administered AISPc, and the dose and time
      post-sensitization of 675 nm light administration. There was no effect on tumour
      or normal brain if the sensitizer dose was less than 0.5 mg/kg. Selective
      necrosis of tumour was evident 6 hours post-sensitization at an AISPc dose up to
      1 mg/kg and light doses up to 200 J/cm(2). Necrosis occurred in normal brain at
      higher doses of light and sensitizer. There was no photosensitizer effect in
      animals treated 24 hours post AISPc administration. The ability of AISPc to act
      as a selective photosensitizer causing photonecrosis provides a basis for the
      generation of modified AISPc species as future agents in the PDT of brain
      tumours, especially as these sensitizers absorb light at a higher wavelength than
      those that are currently available.

PMID- 18638802
TI  - Chronic intraventricular norepinephrine and delayed neuronal death in the
      hippocampus.
AB  - The present studies evaluated the effect of chronic intraventricular
      microinfusion of norepinephrine (NE) to examine if higher levels of intracerebral
      NE could protect agonists the development of delayed neuronal death (DND) in the
      hippocampus of a transient forebrain ischaemia model. Small cannulas connected to
      osmotic minipumps were stereotactically placed in the lateral ventricle, and NE
      (40 muM) was pumped at the rate of 0.5 mu1/hour for periods of up to 14 days.
      Brain tissue was then analysed for the total NE content at 2.5 mm intervals from
      the cannula tip, using high pressure liquid chromatography. The result of these
      preliminary studies showed a 5 to 40-fold increase in the NE levels in the
      specimens on the infusion side and a 2 to 3-fold increase on the non-infusion
      side. The number of surviving pyramidal neurones in the hippocampal CA1 region
      were then compared between the ipsilateral and contralateral hemispheres of the
      brains obtained from experimental and control animals. Significant suppression of
      neuroanal death was demonstrated in the presence of increased levels of exogenous
      NE on the infusion side. These studies suggest that intraventricular
      administration of NE is feasible and that the resulting higher levels of NE may
      attenuate the phenomena of DND in the hippocampus, possibly by a direct
      protective action upon the neurones.

PMID- 18638803
TI  - Epilepsy-from the Sakikku to hughlings Jackson.
AB  - The phenomena of epilepsy have been known for over 3000 years. The earliest
      recorded account is an Akkadian text, the Sakikku, written around 1067-1046 BC.
      Until comparatively recent times popular belief held epilepsy to be a disorder of
      supernatural origin, e.g., due to demonic possession. However, there were other
      interpretations, e.g. a consequence of sinning or of lunar or magical influence.
      Such ideas began to die out only in the past 200 years. From Hippocrates (c. 400
      BC) onwards, there has been a continuing alternative line of thought that
      epilepsy is an ordinary medical condition with a natural cause. The hypothese
      concerning its pathogenesis have ranged from excess phlegm in the ventricles of
      the brain, through boiling up of the 'vital spirits' in the brain (Paracelsus),
      explosion of 'animal spirits' in the centre of the brain (Willis), heightened
      reflex activity at a spinal (Marshall Hall) or medullary level (brown-Sequard),
      to Hughlings Jackson's (1870) notion of 'an occasional, an excessive, and a
      disorderly discharge' in part of the cerebral cortext. At the time Jackson's
      concepts began to be known, an effective treatment of epilepsy (potassium
      bromide) had recently appeared after centuries of ineffective medical measures.
      Since the 1860-1870 decade, epileptology has proved largely a matter of exploring
      the ramifications of Jackson's insights and of developing the therapeutics of the
      disorder in the awareness that effective treatment of possible.

PMID- 18638804
TI  - Recurrent lymphomatoid granulomatosis and isolated CNS involvement.
AB  - Lymphomatoid granulomatosis is a diseases affecting the pulmonary system which is
      not usually associated with involvement of the central nervous system (CNS).
      Isolated central nervous system involvment is rare. This case, of a 65-year-old
      male, was notable not only as a case of lymphomatoid granulomatosis with isolated
      central nervous system involvement, but also with the unusual occurrence of a
      temporal pattern of regression and recrudescence of individual lesions not
      related to therapeutic intervention.

PMID- 18638805
TI  - Multiple neurofibromas of the spinal nerve roots.
AB  - This report describes a rare case of a suspected neurofibromatosis type 1 patient
      who had multiple bilateral spinal neurofibromas from the cervical to the sacral
      spinal dorsal nerve roots. The lesions were readily detected by MR imaging and
      the largest tumour was successfully resected. We provide a brief review of the
      literature, emphasising the usefulness of MR imaging in the diagnosis and
      evaluation of spinal neurofibromas.

PMID- 18638806
TI  - Rapidly progressive Whipple's disease of the central nervous system.
AB  - We describe a patient with rapidly progressive Whipple's disease confined to the
      central nervous system (CNS). The diagnosis was made pre-mortem following
      stereotactic and open brain biopsis and confirmed at autopsy. Despite appropriate
      antibiotic treatment, the disease ran a fulminant course to death after nine
      weeks.

PMID- 18638807
TI  - Properties of cell cultures containing the citrus exocortis viroid.
AB  - Cell and protoplast-derived callus and suspension cultures from healthy and
      citrus exocortis viroid (CEV)-infected tomato tissue have been established. The
      growth rates of CEV-containing cells is not affected by the presence of the
      viroid. In addition, the viroid-containing cells demonstrate a higher temperature
      tolerance for growth. The cell wall structure of infected tissue apparently
      differs from healthy cells as suggested by the differential release of
      protoplasts and the increased yields of protoplasts from infected cells in the
      presence of beta-1,3-glucanase. This biochemical distinction also persists in
      cell suspension cultures. The relationship between the cell wall anomaly and the
      increased frequency of plasmalemmasomes in CEV-containing callus cells is
      discussed.

PMID- 18638808
TI  - Plant virus-specific transport function. I. Virus genetic control required for
      systemic spread.
AB  - Complementation of tobacco mosaic virus (TMV) mutant LS1 which is temperature
      sensitive (ts) in virus transport function was studied in two model systems. The
      first one was aimed at complementing LS1 cell-to-cell spread through the tissues
      of the plant systemically preinfected with a temperature-resistant (tr) virus.
      Two different experiments were performed in this model system. (a) Use was made
      of a host plant which reacted differently to LS1 (local lesions) and to the
      helper virus (systemic reaction) at a permissive (24 degrees) temperature.
      Complementation occurred in a mixedly infected plant at a temperature which is
      nonpermissive for LS1 (32 degrees), when the necrotic reaction of the host was
      switched off; the complementation could be revealed upon the temperature shift
      treatment (TST) (24 --> 32 --> 24 degrees ). (b) Transport of LS1 from cell to
      cell in the presence of the helper virus was tested directly by immunofluorescent
      microscopy. In the second model system, the effect of virus transport from the
      conducting tissues of the stem into the cells of the leaf mesophyll, preinfected
      with the helper virus, was studied. It was shown that ts mutant LS1, imbibed
      through the stem, can move into and replicate in the mesophyll cells of the leaf
      which was preinfected with a tr-helper virus. This was true both at 24 and 32
      degrees . On the other hand, LS1 itself could serve as a helper virus only at 24,
      but not at 32 degrees . In both model systems, it was demonstrated that ts
      transport can be complemented not only by a related tr TMV strain, but also by an
      unrelated virus-potato virus X. It has been suggested that a virus-specific
      transport function performed by the helper virus "opens the gates" for the
      dependent virus by an unknown modification of host cells.

PMID- 18638809
TI  - Plant virus-specific transport function. II. A factor controlling virus host
      range.
AB  - An experimental system allowing the transport of the dependent virus from the
      conducting tissues into the leaf mesophyll of a plant preinfected by the helper
      virus has been developed recently [Taliansky et al. (1982). Virology 122, 318
      326]. The role of virus-specific transport function in the host range control of
      a plant virus was studied here by this technique. It was shown that Tm-2 tomato
      lines (in which the resistance to TMV is expressed only at the level of the
      intact plant, but not in protoplasts) became susceptible to TMV after
      preinfection with the helper virus (potato virus X, PVX). It is assumed that TMV
      accumulation in Tm-2 lines under these conditions becomes possible due to the
      transport function coded for by the helper virus (PVX), which allows TMV to
      spread over the resistant plant. Tm-1 tomato lines (whose protoplasts are
      resistant to TMV infection) remained resistant to TMV under the conditions
      outlined above. It was found that brome mosaic virus (BMV) can be transported
      from the conducting tissues and replicates in the mesophyll cells of tomato and
      bean plants preinfected by TMV and dolichos enation mosaic virus (DEMV),
      respectively. The same was true of TMV introduced into the conducting tissues of
      wheat plants preinfected with barley stripe mosaic virus (BSMV). It is concluded
      that a nonhost plant, whose resistance to a virus is due to the blockage of the
      transport function, can be infected systemically by this virus as a result of the
      complementation of transport with the helper virus.

PMID- 18638810
TI  - Characterization of monoclonal antibodies to the Autographa californica nuclear
      polyhedrosis virus.
AB  - Mouse hybridomas which produce monoclonal antibodies to the Autographa
      californica nuclear polyhedrosis virus (AcNPV) have been prepared and the protein
      to which each is directed has been determined. The antibody produced by clones
      3F3 and 5E9 specifically bound polyhedron protein of MW 32,000 when used in
      immunoadsorption chromatography When used in ELISA they could not distinguish
      between insect- and cell culture-derived polyhedron protein and also reacted with
      a wide range of baculoviruses. The antibody produced by clone 3D10 specifically
      immunoprecipitated a polypeptide of MW 42,000 from tissue culture-derived
      extracellular virus which was a prominent product synthesized in infected cells.
      This polypeptide was a major component of enveloped virus, released from insect
      derived polyhedra, and nucleocapsids. In contrast to 3F3 and 5E9, this antibody
      was specific for AcNPV.

PMID- 18638811
TI  - Mapping of the coat protein gene of cauliflower mosaic virus by its expression in
      a prokaryotic system.
AB  - Polypeptides recognized by antisera to cauliflower mosaic virus (CaMV) coat
      protein were found in lysates of Escherichia coli cells that carry the complete
      CaMV genome on plasmid vectors. Synthesis of this cross-reacting material in E.
      coli was detected when the complete CaMV DNA sequence was present at either of
      two sites and in either orientation at one site of the cloning vector, suggesting
      prokaryotic promoter activity for some sequence within the viral DNA. Using an
      immunosorbent assay to screen subclones containing various segments of the CaMV
      genome, open reading region IV alone was found to be sufficient for synthesis of
      the antigen, thereby mapping the coat protein gene to this region.

PMID- 18638812
TI  - The synthesis and processing of the proteins of bean pod mottle virus in rabbit
      reticulocyte lysates.
AB  - Translation of the two RNA components (B-RNA and M-RNA) of bean pod mottle virus
      (BPMV) in rabbit reticulocyte lysates resulted in the formation of a specific set
      of proteins. Among the products formed was a viral protease that catalyzed the
      cleavage of two precursor proteins coded by M-RNA. The protease showed some
      specificity for BPMV proteins in that it did not cleave the proteins of cowpea
      mosaic virus (CPMV), which is related to BPMV. Conversely, the synthesized BPMV
      precursor proteins were not cleaved by a CPMV protease.

PMID- 18638814
TI  - The epidemiology of central nervous system tumours;trends and risk factors.

PMID- 18638813
TI  - Infection of turnip protoplasts with cauliflower mosaic virus DNA.

PMID- 18638815
TI  - Personal view-implications of predictive genetic testing for Alzheimer's disease.
AB  - Alzheimer's disease is the commonest single cause of adult dementia, and is
      increasing in importance as a publichealth issue as the age structure of
      industrial societies changes. Perhaps 40% of Alzheimer's disease is familial; and
      although at least four different loci have been implicated, it is fairly likely
      that the genetic defects responsible will have been defined fully by the end of
      the millennium. This will place great pressure on clinical genetics services to
      perform predictive genetic testing on "at risk" individuals; but this will raise
      a number of psychological, social, and ethical problems, especially in the
      absence of preventative or curative treatment. Many of these dilemmas have
      already been faced in the context of screening for Huntington's disease, and are
      discussed in the light of this experience. The logistic problems involved in
      predictive testing for Alzheimer's disease will also be considerable. It would
      seem desirable that these issues are considered in advance, and that reasonable
      guidelines for testing are discussed and agreed upon before problems due to
      inconsistent approaches arise.

PMID- 18638816
TI  - Epidemiology of head injury in rural Taiwan -a four year survey.
AB  - An epidemiological study of head injury in Hualien County, Taiwan, was undertaken
      from January 1, 1988 to December31, 1991. The age-adjusted incidence rate of head
      injury was 382/100 000, 499/100 000 for males and 244/100 000 for females. The
      highest incidence rate was observed in the elderly group 70 years or older. It is
      notable that 79% of head injuries were associated with traffic accidents, 75% of
      which directly involved motocycle use. The age-adjusted mortality rate was 89/100
      000 per year, 125/100 000 for males and 47/100 000 for females. As to the
      severity of head injury, the elderly group presented the highest percentage of
      moderate to severe degrees of injury as well as mortality. The victims of
      motorcycle accidents and pedestrians had the highest percentage of relatively
      severe head injury. Hospitalised patients showed an outcome worse than that ever
      reported in the literature.

PMID- 18638817
TI  - Diffuse axonal injury A clinical and computerised tomography study of 128
      patients.
AB  - A study of clinical, computerised tomography (CT) profile and outcome was made of
      128 patients, diagnosed to have diffuse axonal injury based on CT criteria. The
      mean age was 26 years. A lucid interval was present in 37 patients and hypoxia
      and/or hypotension was present in 43 patients. The depth of "marker lesions" in
      CT correlated with Glasgow Coma Score (GCS) (p<0.02) and duration of coma
      (p<0.01). The presence of associated intracranial haematoma >25 ml portended an
      adverse outcome. A logistic regression analysis revealed age, GCS, state of
      perimesencephalic cisterns and pupillary dilation to be independent predictors of
      poor outcome. Residual sequelae (focal deficits, cognitive deficits,
      postconcussion syndrome) were evident in nearly half of patients with diffuse
      axonal injury (DAI) and a lucid interval.

PMID- 18638818
TI  - Familial cavernous angioma without clinical haemorrhage.
AB  - The incidence and natural history of cerebral cavernous malformations remain
      poorly defined. MRI now provides anaccurate means of diagnosis and follow-up of
      these lesions. Hereditary cavernous angiomata have been reported in several
      racial groups, revealing asymptomatic family members with significant numbers of
      lesions. We report a family of Anglo-Saxon origin with nine members among three
      generations affected via an autosomal dominant mode of inheritance. MRI of seven
      affected family members revealed 74 lesions. Autopsy of two further family'
      members who died of unrelated causes also demonstrated the presence of cavernous
      angiomata. No lesion was associated with anomalous venous drainage. Two affected
      family members had seizures. Although six lesions exhibited the characteristic
      mixed intensity T2 spin echo signal suggesting haemorrhage, no lesion has caused
      a clinically apparent haemorrhage. This family offers a unique perspective of the
      natural history of this disease. No clinically apparent haemorrhage has occurred
      in 2418 lesion years. The benign nature of these lesions suggests that, in
      clinically unruptured familial cavernous angiomas, without accompanying anomalous
      venous drainage, a conservative approach may be warranted irrespective of their
      location.

PMID- 18638819
TI  - Frontotemporal orbitozygomatico-alar approachfor skull surgery.
AB  - Mobilisation of the zygoma has been reported to offer excellent exposure of the
      cranial base with minimal brain retraction. This study describes our operative
      technique and presents our experiences of 22 patients. Fifteen patients had a
      skull base neoplasm and 7 had a complex cerebral aneurysm. To facilitate access
      to these lesions, two separate bone flaps were created: (1) A free frontotemporal
      bone flap; and (2) en bloc removal of the superior and lateral orbital rims with
      the attached zygomatic arch. Because the latter bone flap includes both the
      orbital roof and the posterolateral wall of the orbit with the greater wing of
      the sphenoid bone, unnecessary bony defects which could cause enophthalmos or
      other cosmetic problems are avoided. Among the 22 patients, 17 have returned to
      their previous life style and four require assistance for personal care.
      Operative mortality was zero. The incidence of postoperative complications
      directly related to this approach was minimal and cosmetic results were
      acceptable in most patients. We recommend this approach for medially located
      skull base neoplasms or complex cerebral aneurysms.

PMID- 18638820
TI  - Magnetic resonance angiography of hypertensive intracerebral haemorrhage.
AB  - Six patients with hypertensive intracerebral haemorrhage (HIH) were evaluated by
      both computed tomography (CT)and magnetic resonance (MR) angiography. The
      patients underwent MR angiography based on both time-of-flight (TOF) and phase
      contrast (PC) methods. The CT scans showed putamenal haemorrhage in all patients.
      Early operations were performed and the haematoma was removed by stereotactic
      aspiration or a transsylvian approach in all cases. MR angiography offers great
      promise to distinguish HIH from other cerebrovascular diseases. The TOF method is
      very convenient for simultaneously observing both the intracerebral haematoma and
      the cerebral vasculature.

PMID- 18638821
TI  - Temporal lobectomy for epilepsy - complicationsin 200 patients.
AB  - At the Austin Hospital, Melbourne, Australia, 200 consecutive temporal
      lobectomies were performed for refractorycomplex partial seizures between 1969
      and 1991 as part of its Comprehensive Epilepsy Program. The complications of this
      retrospective series are reported. There were no 30-day postoperative deaths but
      there were 6 late deaths. Complications are divided into 'major' if permanent
      and/or severe or 'minor' if temporary or not severe. Complications included
      hemiparesis (2% major, 1% minor), visual field defect (3% major, 18. 5% minor),
      dysphasia (96 dominant resections - 0% major, 5. 5% minor), memory impairment (1
      % major, 9. 5% minor); intracranial infection (2% major, 0% minor), and
      miscellaneous (11 % minor). The mechanisms of the complications are discussed.
      Temporal lobectomy for the treatment of epilepsy can be performed with a low
      morbidity.

PMID- 18638822
TI  - A standardisable model of focal cerebral ischaemia innormotensive rats.
AB  - In this study various techniques with different periods of ischaemia have been
      used in order to describe a standardisable and reproducible model of reversible
      focal cerebral ischaemia in normotensive rats. Cerebral blood flow to the left
      hemisphere of the rats was temporarily interrupted by middle cerebral artery
      occlusion only in four rats of each group, by simultaneous middle cerebral artery
      and ipsilateral common carotid artery occlusion in six rats of each group, and by
      middle cerebral artery and bilateral common carotid artery occlusion in six rats
      of each group. Within each group temporary ischaemia lasted for 1, 2 or 3 h and
      animals survived for 24 h following reperfusion. An infarct of significant size
      with low standard deviation was observed after 3 h of distal middle cerebral
      artery and bilateral common carotid artery occlusion followed by 24 h of
      reperfusion. We have found that the ratio of the infarct volume to the
      supratentorial brain volume is a more reliable criterion (with less standard
      deviation) than infarct volume alone and could be used for comparison of results
      obtained in experimental studies.

PMID- 18638823
TI  - Endothelin-1 levels in plasma and cerebrospinal fluidfollowing subarachnoid
      haemorrhage.
AB  - A serial measurement of endothelin-1(ET-1) levels in plasma, cisternal and
      ventricular cerebrospinal fluid(CSF) was performed in 16 patients with
      subarachnoid haemorrhage (SAH). The patients were classified as grade III or IV
      according to the clinical grade of Hunt and Hess, and computerised tomography(CT)
      was classified as Fisher's CT group 3. Cisternal and ventricular CSF and plasma
      were obtained from the patients on the day of operation days 0-3, days 5-8 and
      days 14-18 after SAH. ET-I concentration in each sample was quantified by
      sandwich-enzyme immunoassay. ET-I levels in plasma and CSF were the highest
      between days 0-3 and then decreased. The ET-I levels in the cisternal CSF were
      significantly higher during days 0-3(p<0. 01) and days 5-8(p<0. 01) than those in
      the ventricular CSF It is suggested that ET-I could play an important role in the
      early stages of the cerebral vasospasm.

PMID- 18638824
TI  - Trepanation in the South pacific.

PMID- 18638825
TI  - Solitary spinal epidural cavernous haemangioma presenting as acute epidural
      haematoma.
AB  - This report describes a case of solitary spinal epidural cavernous haemangioma
      presenting as an acute epiduralhaematoma. The patient is a 50 year old diabetic
      female with right brachalgia and hemiparesis. Magnetic resonance imaging (MRI)
      demonstrated the presence of a cervical spinal epidural haematoma. The patient
      underwent laminectomy and total removal of the haematoma and the accompanying
      vascular tissue. The diagnosis of cavernous haernangioma was proven by
      histological examination. Because the source of bleeding in most cases of
      spontaneous spinal epidural haematoma is usually obscure, the authors emphasise
      the possibility that a small cavernous haemangioma can be one of the bleeding
      sources in some of these cases.

PMID- 18638826
TI  - Adult polycystic kidney disease and arachnoid cyst formation: Case report.
AB  - A 34 year old man is reported with adult polycystic kidney disease with an
      associated extensive arachnoid cyst occupyingmost of his left hemicranium. The
      aetiology of arachnoid cyst formation is discussed.

PMID- 18638827
TI  - Dural arteriovenous malformation causing brainstem haemorrhage.
AB  - A 40 year old man developed a brainstem haemorrhage from an arteriovenous
      malformation of the tentorial incisura. Although the location of the haemorrhage
      represents a unique report, this case illustrates 3 important points that can be
      generally applied to dural arteriovenous malformations. Firstly, the dangers of
      dural arteriovenous malformations with cortical venous drainage. Secondly, with
      regards their risk of haemorrhage, dural arteriovenous malformations (tentorial
      arteriovenous malformations in particular) cannot be dismissed as benign until
      angiography has been performed. Finally, angiography performed for the purpose of
      investigating the possibility of an arteriovenous malformation being responsible
      for an intraparenchymal haemorrhage cannot be considered truly negative unless
      the external carotid circulation has failed to demonstrate an arteriovenous
      malformation in addition to the internal carotid and vertebral circulations.

PMID- 18638828
TI  - Neurodegenerative diseases of the elderly.

PMID- 18638829
TI  - Brain protection during neurosurgery: an update from the anaesthetist's
      perspective.
AB  - Brain protection is defined as measures instituted before a potential insult to
      prevent or ameliorate brain damage, or measures undertaken after an insult to
      protect the brain from secondary damage. Potential brain protection modalities
      during neurosurgery include hypothermia, anaesthetic agents, specific inhibitors
      of peri-ischemic events, induced hypertension and haemodilution. Available
      evidence suggests that we should induce mild hypothermia ( approximately 34
      degrees C), as it has proven benefit in animal studies, and may have fewer side
      effects than high doses of anaesthetic agents. Well conducted anaesthesia with
      any of a variety of agents probably affords similar protection. Experimental
      agents now in development may provide specific protective effects in the future,
      but have the disadvantage that most affect only one factor in a complex sequence
      of neurochemical and ionic events during ischaemia.

PMID- 18638831
TI  - Some principles in neurosurgery.

PMID- 18638830
TI  - Changing the old order: neurosurgery and ethics at the millennium.
AB  - The profound changes in biotechnology which have challenged established beliefs
      in western society over the last 30 years have resulted in ethical problems which
      affect neurosurgeons no less than other medical scientists. This paper examines
      some of these changes in the context of neurological aspects of bioethics and
      argues a justification for the active involvement of clinical neurosurgeons in
      the vigorous debates in society today. In order to adapt to these changes,
      neurosurgeons will need to learn about ethical systems as utilities to resolve
      the conflicts thrown up by biotechnology and pay particular attention to such
      diverse issues as the quality of training programs, continuing medical education,
      the establishmnt of standards of care and membership of Institutional Ethics
      Committees.

PMID- 18638832
TI  - Stereotactic craniotomy for lesions in eloquent areas.
AB  - CT compatible stereotactic systems are being increasingly used in the management
      of intracranial mass lesions. This study deals with the use of BRW stereotactic
      system for excisional biopsy of small (<30 mm), superficial, solitary cerebral
      lesions located in eloquent areas. Out of a total of 113 cases of stereotactic
      craniotomy carried out in the department since 1987, 78 fitted the above
      criteria. Out of these 78 patients, 70 lesions (90%) were less than 20 mm in
      size. Local anaesthesia was used in 10 cases (13%) whereas the rest had general
      anaesthesia. Cortical incision using standard techniques were used in 51 patients
      (65%), whereas in 27 patients (35%) excisional biopsy was done using trans-sulcal
      microsurgical techniques. Twenty-one (41%) patients had some degree of
      neurological deficit in the immediate postoperative period when a cortical
      incision was used compared to 4 patients (15%) when a trans-sulcal microsurgical
      excisional biopsy was done (P < 0.05). However, significant neurological deficits
      were present in 10 cases (12.8%) and all but two had had cortical incisions. When
      assessed one month after surgery significant residual deficit was present in only
      2 patients (2.5%) who had had cortical incisions. There was no postoperative
      infection or mortality in this series. CT guided stereotactic craniotomy coupled
      with trans-sulcal microsurgical techniques can be safely used for the excisional
      biopsy of small superficial lesions located in eloquent areas of the brain.

PMID- 18638833
TI  - Colloid cysts of the third ventricle: fatal outcomes associated with unusual
      presentation.
AB  - It is always unfortunate when benign, surgically removable lesions cause
      unnecessary death. In three of five cases of third ventricular colloid cyst the
      patients presented with or developed severe headache which was like no other they
      had experienced before. The headache was of long enough duration to enable
      detection and removal of the cyst before its fatal outcome. In one case involving
      a fight it was considered that the third vetricular colloid cyst played an
      important part in the fatal outcome. In the fifth case the patient was found dead
      in bed without any preceding history of illness.

PMID- 18638834
TI  - Management of small arteriovenous malformations of the brain.
AB  - A consecutive series of arteriovenous malformations of the brain, no greater than
      3 cm in diameter, referred to the author between January 1989 and October 1994 is
      reviewed. Of these 42 cases 39 underwent surgical excision of the lesion. The
      surgical group had mortality, 2.5% morbidity and 100% angiographic cure. Surgery
      in non-eloquent brain (n=21) resulted in no neurological morbidity and surgery in
      eloquent brain (n=18) resulted in a 5.5% neurological morbidity. The reason for
      not operating in three cases was elderly age in one, poor neurological condition
      in one, and involvement of the posterior limb of the internal capsule in one.
      Arteriovenous malformations with diameters no greater than 3 cm are considered by
      some to be suitable for treatment by focussed irradiation. However, surgery is
      likely to remain the more effective and safer mode of treatment for the majority
      of cases when factoring in the expected complications of focussed irradiation
      during the latency period. These risks are discussed.

PMID- 18638835
TI  - Anti-Yo positive paraneoplastic cerebellar degeneration: a report of three cases
      and review of the literature.
AB  - Anti-Yo is an anti-Purkiney cell cytoplasmic antibody found in approximately 50%
      of patients with parancoplastic cerebellar degeneration (PCD). We report three
      patients with anti-Yo positive PCD (one ovarian carcinoma and two poorly
      differentiated adenocarcinomas consistent with breast origin). Two were treated
      with chemotherapy and plasmapheresis but died within months of the diagnosis from
      progressive neurological disease. The other was given gamma-globulin and has
      remained table at 6 months follow up. Anti-Yo antibodies are highly specific with
      almost all patients having breast or gynaecological malignanies. Commonly the
      tumour is of small volume and asymptomatic. Attempts at treatment are usually
      unsuccessful but there are a number of reports of stabilisation or improvement
      when treatment is begun before the development of severe neurological disability.
      The detection of anti-Yo antibodies is very useful for the diagnosis of PCD
      allowing early tumour detection and prompt institution of treatment.

PMID- 18638836
TI  - Clinical features and SPECT scanning in presumed cortico-basal ganglionic
      degeneration.
AB  - Eight patients presented with a strikingly similar core syndrome of asymmetric
      upper limb rigidity and dystonia (which was maximal in the non-dominant limb in
      seven), accompanied by ipsilateral ideomotor apraxia, cortical sensory
      disturbane, and sensory reflex myoclonus. The clinical diagnosis in each case was
      of presumed cortico-basal ganglionic degeneratioan. The clinical features in our
      cases matched those of other series closely, except for a higher prevalence of
      dementia (presumably explained by referral bias), and a lower incidence of
      oculomotor abnormalities. Seven of the eight patients underwent (59)Tc-HMPAO
      SPECT scanning, which in each case revealed contralateral fronto-parietal
      perfusion defects out of proportion to the focal or generalised atrophy
      demonstrated on MRI scans. SPECT scanning appears to be a useful confirmatory
      investigation in patients presenting with this uncommon but distinctive clinical
      syndrome, and in separating them from patients with other causes of asymmetric
      rigid syndromes, such as Parkinsons's disease.

PMID- 18638837
TI  - Neuroanatomical and cranial geometry of the frontal horn of the lateral
      ventricle.
AB  - In common practice ventricular catheterisation is dependent on accurate targeting
      of the lateral ventricles from external cranial landmarks. A ventricular catheter
      guide has been developed for rapid and accurate placement of ventricular
      catheters using a percutaneous technique and a narrow twist drill. Correct
      intraventricular placement is dependent on the width of the lateral ventricle and
      its distance from the midline, as well as depth from the cranial surface. In the
      present report data is presented obtained from coronal MRI studies describing the
      relationship between ventricular anatomy and cranial geometry. Within the frontal
      quadrant the centre of the frontal horn projection to the cranial surface where
      right angle intersection with the ventricle occurs is 3.28 cm (standard
      deviation, s.d. = 0.26) from the midline, at which point the mean depth from skin
      surface to the frontal horn is 5.97 cm (s.d. = 0.21). Optimal criteria for
      frontal ventriculostomy therefore comprises ventricular catheter passage at right
      angles to the scalp, approximately 3 cm from the midline to a depth of 6 cm from
      the skin where ventricular CSF should be encountered.

PMID- 18638838
TI  - Pharmacological alterations after clot removal in monkey chronic cerebral
      vasospasm.
AB  - An autologous blood clot was placed bilaterally around cerebral arteries in the
      basal subarachnoid space to mimic subarachoid haemorrhage (SAH). Cynomolgus
      monkeys were randomised into five groups: sham operated groups, clot removal
      group at 48, 72 or 96 h after. SAH and clot group. The proximal parts of the
      middle cerebral arteries were cut into rings for isometric tension measurements
      at 7 days after SAH. Potassium chloride, 5-hydroxytryptamine (5-HT),
      norepinephrine (NE), adenosine triphosphate (ATP), prostaglandin F(2alpha)
      (PGF(2alpha)) and haemoglobin all induced dosed-dependent contractions. There was
      a progressive attenution of the contractions in response to the agonists in the
      clot removal and the clot groups, which reached statistical significance at 48 h
      after SAH in the case of 5-HT, and at 72 h in the cases of NE, ATP and
      PGF(2alpha) as compared with the sham operated group. These pharmacological
      results suggest that clot removal should within the first two days after SAH to
      prevnt cerebral vasospasm.

PMID- 18638839
TI  - A rat spinal subarachnoid continuous infusion device.
AB  - In this paper we describe a method for the continuous infusion of putative repair
      enhancing substances into the rat spinal cord subarachnoid space, thereby
      allowing investigation of the process of naturally occurring and graft assisted
      repair of the spinal cord. Solutions are delivered into the rat CSF from an
      osmotic mini-pump via a purpose-made fine-silicone catheter. Under general
      anaesthesia a T13 to L2 laminectomy is performed to expose the dura covering the
      spinal cord. The osmotic mini-pump is placed in a subcutaneous pouch in the left
      thoracolumbar region with the silicone catheter looping forward in the
      subcutaneous plane before entering the subarachnoid space through a durotomy in
      the rostral extent of the exposed dura. A technique of fixation has been
      developed which prevents migration, disconnection or kinking of the mini-pump and
      catheter assembly. Dye infusion, post-mortem and histological studies have been
      used to validate the method and its reliability.

PMID- 18638840
TI  - Juxta-dural ring aneurysms of the internal carotid artery.
AB  - The terminology of juxta-dural ring aneurysms of the internal carotid artery is
      reviewed historically with special reference to those aneurysms protruding
      ventrally. The first description of such cases was made by Drake as exceptional
      examples of carotid-opthalmic aneurysms. Yasargil and Fox termed them ventral
      (inferior) internal carotid artery aneurysms. The term (ventral) paraclinoid
      aneurysms was coined by Nutik. We introduce the concept of carotid cave
      aneurysms. The name superior hypophyseal artery aneurysms was proposed by Day.
      Other related terminologies by various authors are also described.

PMID- 18638841
TI  - Choroid plexus papillomas in childhood.
AB  - Chroid plexus papillomas account for only 0.4-0.6% of intracranial tumours at all
      ages and less than 5% in childhood. Two paediatric cases are reported to
      demonstrate the variability in clinical presentation, location and neurological
      outcome of this benign tumour. One case has been followed for 13 years.

PMID- 18638842
TI  - Internal carotid artery occlusion in adult moyamoya disease report of two cases.
AB  - Two rare cases of moyamoya disease developing total occlusion of the internal
      carotid artery are reported. Follow up cerebral angiograms demonstrated complete
      occlusion of the internal carotid arteries 4 and 15 years after initial
      angiograms. In these clinical circumstances it appeared that the whole cerebral
      blood flow was supplied entirely from the external carotid circulation. It has
      been thought that carotid occlusion was representative of the natural history of
      moyamoya disease. However, progressive total occlusion of the internal carotid
      artery has not previously been reported in this disease. This report provides an
      insight that proximal occlusion is the end-point of the disease.

PMID- 18638843
TI  - Ictal single photon emission computed tomography in seizures induced by eye
      closure.
AB  - Ictal single photon emission computer tomography (SPECT) studies were performed
      on a 12 year old child with reflex seizures induced by eye closure. EEGs had
      shown generalised polyspike waves during eye closure. A magnetic resonance head
      scan was normal. There was no photosensitive induction of the seizure. Comparison
      between ideal and post treatment (ethosuximide) interictal SPECT revealed
      increased ictal perfusion in the basal ganglis, lateral frontal region and
      superior temporal lobe in the left hemisphere. It is suggested that the reflex
      epilepsy in this case was triggered by sensory afferents from the orbicularis
      oculi and mediated via the thalamus.

PMID- 18638844
TI  - Coexistence of a laterally projecting C3 carotid aneurysm and a parasellar
      meningioma.
AB  - The coexistence of a symptomatic parasellar meningioma and an unruptured
      laterally projecting C3 carotid aneurysm in a 54 year old female is presented.
      Although the exact location of the aneurysm in relation to the distal doral ring
      could not be determined by preoperative neuroradiological studies, a surgical
      repair of the aneurysm was indicated since both the aneurysm and the meningioma
      could be exposed in the same operative field. All of the meningioma except for
      its dural attachment in the carotid cave was removed. Great care taken when
      drilling the anterior clinoid process as it had been croded by the aneurysm from
      below. The dural ring was tightly adherent to the neck of the aneurysm and had to
      be dissected sharply with a pair of microscissors. A prophylactic high flow EG-M2
      radial arterial bypass graft was used to decrease the risk of stroke in this
      patient who had poor collateral circulation through the anterior and posterior
      communicating arteries. The aneurysm was clipped successfully and the patient was
      discharged without new neurological deficits. Surgical indications and operative
      technique are discussed.

PMID- 18638845
TI  - Highly purified cucumber mosaic virus-induced RNA-dependent RNA polymerase does
      not contain any of the full length translation products of the genomic RNAs.
AB  - The extensively purified RNA-dependent RNA polymerase (RNA replicase) induced by
      infection of cucumber seedlings with cucumber mosaic virus (CMV) was investigated
      to determine whether the enzyme contains full-length translation products of the
      CMV genomal RNAs. Two experimental approaches were used. (1) RNA replicase
      preparations from plants infected with three strains of CMV (Q, P, and T) all had
      almost identical polypeptide compositions, which included a major polypeptide of
      relative mobility on sodium dodecyl sulfate-polyacrylamide gels of Mr, 100,000,
      and two other proteins, Mr 110,000 and Mr, 35,000, present in smaller, varying
      amounts. These polypeptides were unique to enzyme preparations from CMV-infected
      plants and had similar electrophoretic mobilities to the translation products of
      Q-CMV RNAs 1, 2, and 3, respectively. Analysis of the in vitro translation
      products of the corresponding RNAs of the other two strains of CMV showed,
      however, that those of P-CMV RNA 2 and T-CMV RNAs 1 and 3 varied significantly in
      size from the translation products of the corresponding Q-CMV RNAs. (2) Peptide
      mapping studies, using digestion with the V8 protease from Staphylococcus aureus
      or cleavage with CNBr, confirmed that none of these three components of the
      highly purified RNA replicase was a translation product of the CMV RNAs. The work
      reported in this paper, therefore, showed that the full-length translation
      products of the genomal RNAs of CMV were absent from the RNA replicase induced by
      this virus after solubilization and extensive purification.

PMID- 18638846
TI  - Infection of tobacco leaf epidermal protoplasts with tobacco mosaic virus.
AB  - Protoplasts from the epidermal cells of tobacco leaves were prepared and
      inoculated with tobacco mosaic virus. Up to 50% of the protoplasts became
      infected and, within 3 days, contained an average of 5 x 10(5) virus particles
      per protoplast. Hexagonal crystalline inclusions were observed in many of the
      infected protoplasts.

PMID- 18638847
TI  - Size determination of Orgyia pseudotsugata cytoplasmic polyhedrosis virus genomic
      RNA.
AB  - Molecular-weight estimates were determined for the Orgyia pseudotsugata
      cytoplasmic polyhedrosis virus (CPV) genome. The molecular-weight estimates were
      obtained from measurements of glyoxal denatured RNA molecules following
      electrophoresis in 1% agarose gels and electron micrographic contour lengths.
      These estimates were compared to the minimal coding capacity derived from the
      size of translation products of selected genomic segments. The results obtained
      from these different experimental approaches were in sufficient agreement to
      estimate the genome size at 20.4 x 106 (29.8 kbp) with a segmental range from
      0.61 to 3.53 x 10(6) (0.89-5.19 kbp). Two other members of the Reoviridae family
      were examined, the Bombyx mori CPV and the human reovirus type 3 (Dearing
      strain). The molecular-weight estimates for these two viruses were 20.3 and 19.1
      x 10(6), respectively. These results suggest that the previously published
      molecular-weight estimates for these various double-stranded RNA genomes were
      underestimated.

PMID- 18638848
TI  - DNA homology among subgroup A, B, and C baculoviruses.
AB  - The DNA homology among 18 baculoviruses from subgroups A, B, and C was compared
      using restriction endonuclease analysis, DNA hybridization, and Southern blot
      hybridization. Restriction enzyme patterns for each of the viral DNAs compared
      was unique. Viral DNA homology was evaluated by hybridizing 32P-labeled viral
      DNAs to unlabeled DNAs immobilized on nitrocellulose filters. Hybridization
      conditions were varied by using a range of formamide concentrations during
      annealing. The apparent DNA homology among viruses was from 2- to 10-fold
      different depending on the stringency of the hybridization conditions. At the
      least stringent conditions, all viral DNAS from subgroup A, B, and C had
      detectable sequence homology. Homologous DNA sequences were mapped, using
      Southern blot analysis, to several regions of the Autographa californica nuclear
      polyhedrosis virus (AcMNPV) genome. Subgroup A, B, and C viral DNAs had sequences
      homologous to AcMNPV EcoRI fragment I and all subgroup A and B viral DNAs
      hybridized to AcMNPV EcoRl fragments L and M.

PMID- 18638849
TI  - Recent developments in the transmissible spongiform encephalopathies:
      Implications for clinical practice.

PMID- 18638850
TI  - Immunobiology of malignant gliomas.
AB  - The immune system of patients with malignant gliomas is profoundly suppressed.
      The suppression involves both the cellular and humoral immunity and it is mainly
      attributable to selective depletion and malfunction of helper T cells. Malignant
      glioma cells express potent immunosuppressive factors such as transforming growth
      factor-beta(2), inteleukin-10 and prostaglandin E(2). Malignant glioma cells also
      produce chemoattractants and immunostimulatory cytokines which may activate the
      immune cells. However, the production of these stimulatory cytokines is not self
      destructive to glioma cells because of the immunosuppression. Rather, the tumour
      cells use them to gain a growth advantage. Indeed the cytokines may act as a
      growth stimulator of the tumour cells themselves (autocrine mechanism), they may
      act as angiogenic factors to endothelial cells (paracrine mechanism) or induce
      the attracted immune cells to secrete angiogenic factors. Some cytokines produced
      by malignant glioma cells are known to be growth inhibitory to normal astrocytes.
      Recent studies on tumour suppressor genes suggest a close link between the
      aberrant genes and the immunobiologic features of malignant glioma cells.

PMID- 18638851
TI  - Consciousness and the human spirit.
AB  - Consciousness is experienced by all non-sleepers, but not easily understood.
      There is a way in to landmarks through types of question and classes of
      appropriate answers to questions, which combine to define four levels of
      consciousness. These clarify self-knowledge, and the processes of learning and
      decision. Definitions of spirit and matter are offered that acknowledge contrast,
      and conditions of emergence that accept modern logic are pointed to. Since the
      notions of consciousness and of soul apply to powers we share with animals,
      investigation of what is specific to human beings should focus on those levels of
      consciousness which we experience as inquiry, understanding, judging, and
      decision, and on the type of organisation which supports such activities.

PMID- 18638852
TI  - Iatrogenic Creutzfeldt-Jakob disease and its neurosurgical implications.
AB  - Creutzfeldt-Jakob (CJD) disease has been reported after the insertion of dural
      homografts. Two Australian cases of CJD, both following posterior fossa
      craniotomies done in 1982, are reported; the incubation periods were 5 and 12
      years. It seems highly probable that the association is causal. CJD infective
      agents (prions) are resistant to many previously accepted means of sterilisation
      and it is postulated that cadaver dural material was either derived from subjects
      with CID, or was contaminated during preparation. In Australia the use of dural
      homografts in neurosurgery was abandoned in 1987; as the mean incubation period
      (determined from a world-wide review) has been about 65 months, it is now hoped
      that this cause of CJD will not recur in the Australian population, although it
      is premature to state this with confidence. However, precautions against case-to
      case transmission remain necessary, and guidelines for this purpose should be
      enforced in theatre practice and in organ donations.

PMID- 18638853
TI  - Treatment of upper limb dystonia with botulinum toxin.
AB  - The use of botulinum toxin A (BTX A) in upper limb dystonia is gaining increasing
      acceptance and it has recently been suggested that it be considered as first line
      treatment.(1) We have reviewed our experience since 1991 of treating 20 cases of
      upper limb dystonia. 14 patients had task-specific dystonias (6 simple writer's
      cramp, 5 dystonic writer's cramp, 3 musician's cramp) and 6 had secondary focal
      or segmental dystonias (4 with early cortico-basal degeneration). All patients
      had electromyography to both determine and guide muscle selection. Pre- and post
      treatment video as well as questionnaires formed the basis for outcome
      assessment. Botulinum toxin therapy was clearly beneficial in about two-thirds of
      those with primary upper limb dystonia, a condition affecting young adults (mean
      onset 32.9 years). In contrast, BTX A was far less effective in secondary upper
      limb dystonias which occurred in the elderly (mean onset 71.7 years). Optimal
      treatment strategies are discussed. In conclusion, botulinum toxin is an
      effective form of treatment for primary upper limb dystonia; its role in late
      onset secondary dystonia is mainly palliative.

PMID- 18638854
TI  - Injection of hot saline into sympathetic ganglia for palmar hyperhidrosis.
AB  - Palmar hyperhidrosis is a disease frequently encountered in Vietnam. It is a
      severe social and professional handicap for the patient. More than 300 patients
      with palmar hyperhidrosis had been treated by classical upper thoracic
      sympathectomy in the Department of Neurosurgery in the Viet Duc Hospital up to
      May 1977. Faced with an increasing number of patients, a non-surgical treatment
      was therefore advocated. The technique consists of bilateral percutaneous
      injection of boiling saline into the paravertebral area containing the upper
      sympathetic ganglia. From May 1977 to January 1989, 600 patients were treated by
      this new technique. An objective reliable criterion of the success of the
      procedure is arterial vasodilatation in the upper limb, evidenced by pre- and
      postoperative Doppler studies and accompanied by dryness of the hands. Good
      results were obtained in 71% of the patients, bad results in 18% and relapse in
      11%. Two major complications were Horner's syndrome (immediate in 14%, late in
      1%) and compensatory hyperhidrosis (65%). The results show the effectiveness of
      non-surgical sympathectomy, with the advantages of greater simplicity and lower
      cost.

PMID- 18638855
TI  - Recanalisation and outcome cerebral venous thrombosis.
AB  - Little is known of the natural history and rate of sinus recanalisation after
      cerebral venous thrombosis (CVT). Although acute anticoagulation is effective,
      the duration of therapy remains speculative. We aimed to determine the
      relationship between sinus recanalisation and clinical outcome. We studied 12
      consecutive patients with aseptic CVT with evidence of sinus thrombosis on
      initial magnetic resonance imaging, followed up 5-68 months after onset, using 15
      repeat magnetic resonance scans in 9 of the patients to assess recanalisation.
      All patients initially had one or more thrombosed sinuses and were treated with
      anticoagulants for at least 6 months, including 3 with haemorrhagic infarction.
      Residual neurological deficits were present in only one patient. No patient had a
      recurrent thrombosis. Recanalisations was incomplete in 6 of the 9 cases. Sinus
      recanalisation after cerebral venous thrombosis does not correlate with clinical
      outcome. Although empirical, the general recommendation of 6 months anticoagulant
      therapy is appropriate.

PMID- 18638856
TI  - Outcome of aneurysmal subarachnoid haemorrhage following the introduction of
      papaverine angioplasty.
AB  - This is a prospective study reporting the impact of angiographic vasospasm on the
      outcome following aneurysmal subarachnoid haemorrhage utilising a common regimen
      that includes nimodipine and angioplasty. The first 100 patients suffering an
      aneurysmal subarachnoid haemorrhage treated by surgery and this angioplasty
      driven protocol are reviewed. Angiography was performed if the Glasgow Coma Score
      (GCS) fell by two, a focal neurological deficit developed, hyponatraemia was
      detected, or routinely on days 5-7 following the subarachnoid haemorrhage.
      Angioplasty with papaverine was administered intra-arterially in all patients
      with significant angiographic vasospasm. Neurological deficits on admission were
      not present in 49% and associated with a GCS less than 14 in 38%. Angiographic
      vasospasm was detected in 48% of patients (all of whom received papaverine).
      Overall 3 month outcome was normal in 60%, neurological deficit but independence
      with regard to activities of daily living in 18%, loss of independence in 17%,
      and death in 5% of cases. Analysis of admission neurological condition (GCS < vs
      GCS > 13), presence of angiographic vasospasm, aneurysm size (less than or
      greater than 1.5 cm), and aneurysm circulation (anterior vs posterior) on outcome
      (normal vs abnormal) found that only admission neurological condition
      significantly influenced outcome (P < 0.0001). The results suggest that with the
      protocol of nimodipine and angioplasty the impact of vasospasm on outcome is far
      less significant than the clinical severity of the initial haemorrhage. This is
      in contradistinction to the experience with aneurysmal subarachnoid haemorrhage
      prior to this regimen (nimodipine and angioplasty) where vasospasm was the most
      significant determinant of a poor outcome.

PMID- 18638857
TI  - The Westmead head injury project: Outcome prediction in acute subdural haematoma.
AB  - A prospective two year study of a consecutive sample of patients with an acute
      subdural haematoma who were admitted to Westmead Hospital, New South Wales,
      Australia was undertaken. There were 103 patients with an acute subdural
      haematoma admitted in the period. Twenty-four of these scored 9 or greater on the
      Glasgow Coma Scale (GCS) and of these all made a functional recovery, i.e.
      Glasgow Outcome Scale (GOS 1 or 2). The remaining 79 patients scored 8 or less on
      admission and of these 30% made a functional recovery. Of the 70% remaining, 4%
      were moderately or severely disabled (GOS 3 or 4) while 66% died (GOS 5). Age,
      hypoxia, hypotension, response to intracranial pressure control and two CT scan
      features, midline shift as measured from the septum pellucidum and cerebral
      oedema, were all significant in predicting outcome. Time from injury to
      treatment, initial pupil response, lucid interval and compression of brainstem
      cisterns on CT scans statistically failed to predict outcome. The data were
      analysed using logistic regression which showed age and midline shift to predict
      death or disability with an accuracy of 80% at twelve months after the injury
      (sensitivity 58%, specificity 89%).

PMID- 18638858
TI  - Titanium cranioplasty using 3-D computer modelling of skull defects.
AB  - The ideal prosthesis for cranial defect repair is the original bone flap, but for
      various reasons this is not always available. Creation of prostheses has been an
      inexact and difficult science, particularly for complex and cosmetically
      important defects. Poorly shaped prostheses are difficult to insert and secure.
      In addition, the resultant deformity may lead to scalp necrosis and infection.
      The need for precision-fitting prostheses has prompted the development of several
      computer-aided methods of cranioplasty plate manufacture. Defects have been
      modelled from CT scan data using stacked slices, computer-driven milling and
      selective laser sintering. We report our experience with titanium cranioplasty
      plates manufactured using these methods. The plates fit even the most complex
      defects, are easy to insert, and produce excellent cosmetic results. There has
      been no postoperative scalp necrosis or infection. The cost and time involved may
      currently preclude the routine use of computer modelling of defects, but as
      equipment costs and production time diminish, this may become the standard
      allograft cranioplasty technique.

PMID- 18638859
TI  - Contralateral transcondylar approach for aneurysms of the posterior inferior
      cerebellar artery-vertebral artery complex.
AB  - We report a patient with an aneurysm of the left vertebral artery (VA)-posterior
      inferior cerebellar artery (PICA) complex that was treated successfully via a
      contralateral transcondylar approach. The aneurysm was small, pointed laterally
      to the right, and was located across the midline just above the level of the
      foramen magnum. This unusual location required special consideration during
      diagnostic evaluation and surgical planning. To simulate the operative view, the
      patient's head was turned 45 degrees. This extreme oblique view offered useful
      information with respect to the choice of side from which the surgical approach
      should be made. Removal of the posteromedial part of the occipital condyle
      allowed us to clip the aneurysmal neck without difficulty although the surgical
      approach was made on the side contralateral to the parent artery. We conclude
      that the contralateral approach for VA-PICA aneurysms should be considered when
      aneurysms cross the midline, and that extradural removal of the basal bony
      structures, including the occipital condyle, can provide a wide wirking space
      without excessive retraction on the brain stem.

PMID- 18638860
TI  - Effective management of cerebral vasospasm with balloon angioplasty after failed
      papaverine angioplasty.
AB  - A 37 year old male with symptomatic cerebral vasospasm complicating the rupture
      of a basilar tip aneurysm was initially treated with intra-arterial papaverine in
      conjunction with concomitant hypervolaemia and induced hypertension. However, the
      vasospasm was only moderately improved, with this effect lasting for less than 24
      h. Following further administration of intra-arterial papaverine, without
      significant angiographic improvement, endovascular balloon dilatation of both
      vertebral arteries and basilar artery resulted in dramatic and sustained reversal
      of angiographic vasospasm. The patient's clinical condition improved dramatically
      after this procedure, progressing from an unconscious state requiring ventilatory
      support, to a Glasgow Coma Score of 15 in the absence of focal neurological signs
      (with the exception of a right oculomotor palsy), within 9 days. This case
      suggests that there may be a role for balloon dilatation angioplasty, in patients
      who have cerebral vasospasm refractory to treatment with intra-arterial
      papaverine.

PMID- 18638861
TI  - Symptomatic female heterozygotes for adrenoleukodystrophy: A report of two
      unrelated cases and review of the literature.
AB  - We report two cases of unrelated female heterozygotes for adrenoleukodystrophy
      (ALD) who have developed progressive neurological disease. Both presented with a
      progressive myelopathy in midlife and one has since also developed a peripheral
      neuropathy. Both women had elevated very long chain fatty acid (VLCFA) levels.
      One patient has been on Lorenzo's oil for 2 years with normalisation of her
      plasma VLCFA assays but her condition has progressed relentlessly and the second
      discontinued Lorenzo's oil after 1 month due to unacceptable weight loss. Review
      of the literature reveals that significant neurological symptoms develop in 15
      20% of female heterozygotes and that abnormalities on neurological examination
      occur in up to 55%. Despite a not excessively rare estimated gene frequency of 1
      20,000 the diagnosis of a symptomatic heterozygote for ALD is rarely made in the
      absence of an affected male relative with most patients misdiagnosed as suffering
      from multiple sclerosis.

PMID- 18638862
TI  - Intracranial dural granulomas secondary to operative use of oxidised cellulose.
AB  - A case is presented of intracranial dural granulomata which appear to have
      developed as a reaction to surgical use of oxidised cellulose.

PMID- 18638863
TI  - Spinal and basilar extraparenchymal neurocysticercosis.
AB  - The case of a 40 year old male with spinal and basilar neurocysticercosis is
      presented. After presentation with myelopathy many years later, the original
      diagnosis of aqueduct stenosis is under question. The case and disease process
      are discussed.

PMID- 18638864
TI  - Roasting old chestnuts - consciousness and its meanings.

PMID- 18638865
TI  - Consciousness.

PMID- 18638866
TI  - Ultrastructure of mixed plant virus infection: bean yellow mosaic virus with
      cowpea severe mosaic virus or cowpea mosaic virus in bean.
AB  - Ultrastructural responses of bean leaf cells simultaneously infected with two
      morphologically distinct RNA viruses, cowpea mosaic virus (CPMV) and bean yellow
      mosaic virus (BYMV), or cowpea severe mosaic virus (CSMV) and BYMV, were studied
      in situ. The major effects on cells infected with two viruses included: (1)
      association of virus group-specific cytoplasmic inclusions characteristic of each
      virus; (2) close association of virions into specifically arranged aggregates in
      which CPMV or CSMV icosahedra were aligned along the long axes of the BYMV rods;
      and (3) the induced formation of intranuclear inclusions, spheres (22-26 nm in
      diameter) and filaments (10-14 nm wide and of variable length) in mixed
      infections of CSMV and BYMV. Intracellular serological testing using ferritin
      conjugated with CSMV antibodies revealed no relationship between the spherical
      intranuclear inclusions and CSMV capsids. We conclude that the ultrastructure of
      mixed infections could be used as another tool for identifying related plant
      viruses.

PMID- 18638867
TI  - Translation of red clover necrotic mosaic virus RNA in rabbit reticulocyte
      lysate: identification of the virus coat protein cistron on the larger RNA strand
      of the bipartite genome.
AB  - The bipartite genome of red clover necrotic mosaic virus (RCNMV) was translated
      in nuclease-treated rabbit reticulocyte lysate with the synthesis of three
      principal translation products of molecular weights 39,000, 36,000, and 34,000.
      The 39,000 translation product was shown to be RCNMV coat protein by peptide
      mapping after partial proteolysis and by specific immunoprecipitation. RCNMV coat
      protein was shown to be coded for on the larger RNA (RNA-1) of the bipartite
      genome by hybrid-arrested translation using complementary DNA prepared to each of
      the fractionated RNAS. The 36,000-molecular weight product was also translated
      from RNA-1 while the 34,000-molecular weight product was not. Preliminary
      evidence indicated that the RCNMV coat protein is translated from a subgenomic
      species of RNA-1.

PMID- 18638868
TI  - Characterization of two abundant mRNAs of Autographa californica nuclear
      polyhedrosis virus present late in infection.
AB  - Cytoplasmic poly(A)(+) RNA isolated from Spodoptera frugiperda cells late after
      infection with Autographa californica nuclear polyhedrosis virus (30-40 hr pi)
      was fractionated according to size on denaturing methyl mercury gels. Two major
      RNA species (1.4 kb and 0.75 kb) and several minor RNA species were detected by
      ethidium bromide staining. The predominant RNA species of about 1.4 kb was
      considered to be polyhedrin mRNA because (1) in vitro translation of the RNA,
      which was eluted from methyl mercury gels, yielded a polypeptide of MW 33K, which
      comigrated with polyhedrin. (2) When poly(A)+ RNA was fractionated on a sucrose
      column and then translated in vitro, the distribution and abundance profiles of a
      33K polypeptide product and of 1.4-kb RNA were similar. (3) The 33K polypeptide
      made in vitro and purified polyhedrin gave rise to similar patterns of peptides
      when digested with S. aureus V8 protease. The polyhedrin mRNA (1.4 kb) hybridized
      to BamHI-F and HindIII-V AcNPV DNA fragments and hybridization selection with
      BamHI-F AcNPV DNA yielded a 33K polypeptide, which comigrated with polyhedrin.
      The second RNA species (0.75 kb in size) hybridized to overlapping EcoRI-P and
      HindIII-Q regions of the AcNPV genome and translated into a methionine deficient
      polypeptide of MW = 8K. It was synthesized in large quantities late in the
      infection and appeared to be coordinately expressed with polyhedrin in infected
      cells. The 8K polypeptide was detected as early as 15 hr pi and was still
      synthesized at 60 hr pi.

PMID- 18638869
TI  - Cell-free translation of tobacco vein mottling virus RNA. II. Immunoprecipitation
      of products by antisera to cylindrical inclusion, nuclear inclusion, and helper
      component proteins.
AB  - The genomic RNA of tobacco vein mottling virus (TVMV) was translated in a cell
      free system derived from rabbit reticulocytes. Antisera against TVMV coat
      protein, TVMV cylindrical inclusions, the helper component required for aphid
      transmission of TVMV, and the 49- and 54-kd nuclear inclusion proteins of tobacco
      etch virus (TEV) were used to characterize the translational products. Each of
      the five antisera precipitated a distinctive pattern of polypeptides. Specificity
      of immunoprecipitation was shown by competing with the various proteins to which
      antisera were raised and by sequentially precipitating with two different
      antisera. These experiments showed that the five antisera define five different
      nonoverlapping regions of the TVMV genome.

PMID- 18638870
TI  - Emergence of a new variant of Creutzfeldt-Jakob disease in Europe?

PMID- 18638871
TI  - The swiss society of neurosurgery.

PMID- 18638872
TI  - Multimodal therapy of cerebral arteriovenous malformations.
AB  - Over the last few decades two new modalities of treatment have been added to the
      therapy of cerebral arteriovenous malformations: stereotactic radiosurgery and
      angiographic embolisation. The aim of this review is to discuss surgery and the
      newer modalities of treatment with particular reference to an integrated
      multimodal approach to therapy.

PMID- 18638873
TI  - Professional responsibility: the ethical argument for expert evidence.

PMID- 18638874
TI  - Intracranial arteriovenous malformations in childhood: presentation, management
      and outcome.
AB  - Cases of true intracranial arteriovenous malformations (AVMs) presenting over a
      25 year period were reviewed in order to achieve a better understanding of the
      behaviour and management of AVMs in children. There were 69 cases, presenting
      with haemorrhage (78%), seizures (13%) cardiac failure (3%) and focal signs with
      or without headache (6%). It was less common to present under six years of age.
      CT scanning, where performed, always demonstrated an abnormality, but this was
      suggestive of an AVM in less than one third. By contrast, angiography defined the
      lesion in 82% of initial studies. 59 patients underwent a surgical procedure
      directed at their AVM or an associated haematoma. Total AVM excision was obtained
      in 65%, with none of these later rebleeding. Three patients presenting solely
      with seizures were not operated upon initially, but underwent successful
      resections of their lesions after later haemorrhages. There were 6 (9%) deaths in
      the series, with focal deficits in 52% of survivors at last follow up. In the
      operative group these figures were 3% and 51%, respectively. None of the eight
      patients operated upon prior to a clinical bleed suffered a new neurological
      deficit. The role of stereotactic radiosurgery, although not used in any of our
      cases, is discussed. We believe that our results support an aggressive surgical
      approach to childhood AVMs, regardless of presentation, given the significant
      risk of morbidity from a later bleed, and the lack of a clearly better outcome
      with expectant management or irradiation.

PMID- 18638875
TI  - Principles for managing penetrating craniocerebral injuries caused by firearm
      missiles.
AB  - Penetrating craniocerebral firearm injuries remain one of the most lethal causes
      of all trauma and are common both in war or peace time. Data were reviewed for
      4140 severely head-injured patients (Glasgow Coma Scale (GCS) scores 3-8) treated
      at Xi-Jing Hospital between 1973 and 1993; 51 of these patients had acute
      penetrating craniocerebral injuries caused by firearm missiles. These patients
      consisted of 46 males (90.2%) and 5 females (9.8%) ranging in age from 3 months
      to 48 years (median 22.4 years). The lesion types included 2 tangential wounds,
      37 tubular wounds and 12 through-and-through wounds. All cases were urgent with
      the patients in severe and unstable states. After emergency treatment and
      operation, 5 cases died (9.8%). Follow up studies at three months showed that 23
      cases (45.1%) had made a good recovery. Moderate disability, severe disability
      and vegetative states in this series were 29.4%, 13.7% and 2.0% respectively.
      Long term follow up studies indicated that 32 were able to resume their
      occupation. The principles for managing penetrating craniocerebral firearm
      injuries and suggestions for operation are discussed.

PMID- 18638876
TI  - An Australian multicentre open label study of pergolide as an adjunct to levodopa
      in Parkinson's disease.
AB  - The efficacy and side effects of pergolide, a D(1) and D(2) dopamine agonist,
      were assessed in an open label study in 39 patients with long standing
      Parkinson's disease complicated by end of dose failure and/or dyskinesia. 27
      patients completed 28 weeks of the study. The mean dose of pergolide was 2.26
      mg/day (0.15-5.0mg/day). Levodopa was reduced by a mean of 273 mg/day (range 0
      1950mg/day) from the initial mean dose of 920 mg/day (range 150-2950mg/day).
      Hours in which the drug was efficacious significantly increased. Dyskinesia and
      dystonia were significantly reduced. The scores on an abbreviated Parkinson's
      disease rating scale significantly improved in both the 'on' and 'off' periods.
      11 patients withdrew due to early side effects but the majority of patients
      tolerated pergolide well. In these patients pergolide was an effective adjunct to
      levodopa.

PMID- 18638877
TI  - An appraisal of the clinical use of lamotrigine under the special access scheme.
AB  - This paper studied the use and efficacy of lamotrigine (LTG), one of the newly
      developed antiepileptic medications (AEM), released via the Special Access Scheme
      (SAS). It is argued that the SAS application more closely resembles clinical
      practice and removes the rigours of clinical drug trialing which of themselves
      may impose confounding variables into the interpretation of AEM efficacy. Global
      score evaluation was used to assess efficacy, with scores greater than 4
      indicating improvement. Thirty-two patients were administered SAS-LTG, of whom 30
      were assessable with a mean duration of therapy of 90 weeks. Twenty-eight (93.3%)
      patients were assessed at 6 months; 22 (73.3%) patients were assessed at 12
      months. Patients with generalised epilepsies received lower doses of LTG than
      those with partial seizures although this may reflect the use of concomitant
      sodium valproate (VPA) which is known to increase LTG half life. LTG produced
      statistically greater global scores in patients with generalised epilepsies (mean
      5.6 at 6 months) than for those with partial seizures (mean 4.7 at 6 months).
      Plasma levels of LTG did not contribute greatly to clinical management. It was
      concluded that LTG is a relatively safe and effective AEM for certain patients
      with epilepsy who have proven refractory to the older AEMs. Four patients with
      refractory generalised seizures were rendered seizure free with the addition of
      LTG.

PMID- 18638878
TI  - C1-C2 transarticular screw fixation for treatment of C1-C2 instability.
AB  - C1-C2 instability has traditionally been treated by C1-C2 posterior wiring and
      bone grafting. However, this technique has an incidence of non-union which may
      exceed 10%. Transarticular screw fixation has developed as a technique of
      providing increased strength of fixation of C1-C2 arthrodesis, while at the same
      time avoiding the need for postoperative halo bracing and avoiding the risk of
      neurological injury associated with the passage of sublaminar wires. We present a
      retrospective review of 12 patients with C1-C2 instability treated by C1-C2
      transarticular screw fixation. Eight patients underwent this procedure as primary
      treatment, and 4 after a failed Gallie fusion. Five patients had a cruciate
      ligament rupture, 5 had an odontoid process fracture, 1 had os odontoideum, and 1
      had rheumatoid instability. There was no surgical morbidity or mortality and, at
      a mean follow up of 12.1 +/- 3 months (range 8-14 months), all patients had
      achieved solid fusion, and all neurological symptoms referable to the instability
      had resolved. C1-C2 transarticular screw fixation has been shown to be safe and
      effective and has a number of advantages when compared to traditional posterior
      wiring techniques. We recommend that this technique be considered as a primary
      treatment of C1-C2 instability.

PMID- 18638879
TI  - Classification and treatment of aneurysms of the internal carotid siphon.
AB  - A series of 48 surgically treated internal carotid siphon aneurysms is presented.
      The projection of these aneurysms are a key factor in their surgical repair and
      should be included in a classification system.

PMID- 18638880
TI  - Determination of the activation spectrum of aluminium phthalocyanine chloride
      against cultured meningioma cells using a tunable laser.
AB  - The activation spectrum of the photosensitising agent aluminium phthalocyanine
      chloride (ClAlPc) was determined using cultured meningioma cells as the
      biological target. Cells were irradiated with tunable lasers over the wavelength
      range 605-1000 nm and photocytotoxicity was measured 24 h later by a tetrazolium
      assay. The photoactivation spectrum was found to be relatively narrow with a
      sharply defined maximum at 675-680 nm, a readily accessible wavelength for
      commercially available diode lasers. The absorption spectrum of ClAlPc in aqueous
      solution was broad and featureless, contrasting markedly with the activation
      spectrum. However, as the content of an organic solvent (dimethylsulphoxide) was
      increased, the absorption spectrum progressively resembled the activation
      spectrum. It is concluded that the absorption spectrum of ClAlPc in aqueous
      solution is determined by drug aggregation, which can be prevented by an organic
      environment. This implies that the active form of ClAlPc in cells is the
      monomeric species probably located in cellular membranes.

PMID- 18638881
TI  - A ventricular catheter guide for rapid and accurate ventricular access.
AB  - A ventricular catheter guide for rapid and accurate percutaneous insertion of
      ventricular catheters into the anterior horn of the lateral ventricle is
      presented. It comprises a cylindrical platform with a removable guide tube that
      directs a surgical trajectory for passage of a narrow calibre twist drill and
      ventricular catheter, at right angles to all cranial contours within the frontal
      cranial quadrant. In clinical usage percutaneous ventriculostomy using the
      instrumentation and technique described can be completed within fifteen minutes
      with a single catheter passage through brain, and remain in situ for extended
      periods without evidence of infection on serial cerebrospinal fluid
      microbiological analysis.

PMID- 18638882
TI  - Interlocking detachable coils for spontaneous vertebral arteriovenous fistula.
AB  - We report a case of a spontaneous vertebral arteriovenous fistula treated with
      interlocking detachable coils (IDC). The patient had presented with paroxysmal
      dizziness and a cervical bruit. Angiography demonstrated a high flow
      arteriovenous fistula of the right extracranial vertebral artery. Embolisation
      was performed via the transarterial approach using 2 IDCs. The advantage of IDCs
      in the treatment of high flow arteriovenous fistulae is discussed.

PMID- 18638883
TI  - Progressive visual loss: an unusual presentation of multiple sclerosis.
AB  - Progressive visual loss as a presenting feature of multiple sclerosis (MS) is
      unusual. We report three cases who presented with progressive visual loss and in
      whom MS was diagnosed after other causes of progressive visual loss had been
      excluded. Two of the three had clinical evidence of neurological involvement
      outside the visual pathways. All had lesions consistent with MS outside the
      visual pathways on magnetic resonance imaging. Oligoclonal IgG bands were
      detected in the cerebrospinal fluid but not in the serum of two of the three
      patients. We conclude that MS should be considered in the differential diagnosis
      of progressive visual loss; however, other more common causes of visual loss must
      first be excluded, and there must be positive evidence to support a diagnosis of
      MS.

PMID- 18638884
TI  - Atypical Miller Fisher syndrome with GQ1b antibodies.
AB  - An atypical case of Miller Fisher syndrome is described in a patient with
      ophthalmoplegia and mild ataxia but no areflexia. High titres of acute phase
      antibodies to gangliosides asialo-GM1 and GQ1b were detected. Asialo-GM1
      antibodies have not been previously reported in association with Miller Fisher
      syndrome. Considerable clinical recovery occurred in association with reduction
      in the ganglioside antibody titres. Ganglioside antibody assays may be helpful in
      the diagnosis of atypical cases of Miller Fisher syndrome. Detailed clinical,
      radiological and laboratory evaluation of suspected cases is warranted to improve
      our understanding of Miller Fisher syndrome. Such studies and the correlation
      with ganglioside antibody titres will also provide insights into the relationship
      between the classical and atypical cases of Miller Fisher syndrome, Guillain
      Barre syndrome and Bickerstaff's brain stem encephalitis.

PMID- 18638885
TI  - Interposition saphenous vein bypass graft between the common and intracranial
      internal carotid arteries.
AB  - 22 common carotid to intracranial internal carotid artery bypass grafts with
      interposition saphenous vein were performed in 20 patients over a four year
      period. The distal anastomosis was end-to-end on the internal carotid artery at a
      site between the ophthalmic and posterior communicating arteries. Early occlusion
      (rendered patent with Urokinase) occurred in one graft resulting in fatal
      infarction. Flow included all the anterior and middle cerebral arteries in 17
      bypass procedures and middle cerebral artery only in five bypasses. Complications
      attributable to the bypass were seen following six procedures. These
      complications resulted in mortality in one case (early graft occlusion) and
      permanent morbidity (partial monocular visual loss) in two cases. Other
      complications resulting in no, or temporary, morbidity were cortical infarction
      due to division of collateral meningeal supply during opening (n=1), epidural
      haematoma (n=1), and intimal hyperplasia causing delayed graft stenosis (n=1).
      With the exception of the operative complications no patient subsequently
      experienced a hemispheric ischaemic episode. Minimising complications is possible
      with avoidance of proximal ligation of the internal carotid artery whenever
      possible, ligation of the ophthalmic artery when steal into a cavernous sinus
      fistula is a possibility, careful evaluation of existing collaterals from the
      middle meningeal artery (and their preservation) and attention to timing for the
      postoperative introduction of anticoagulants. Early graft occlusion (4.5%) is
      likely to remain the most feared complication of this procedure. Immediate
      intervention with intragraft Urokinase may re-establish graft patency.

PMID- 18638886
TI  - Cavernous sinus: a speculative note.

PMID- 18638887
TI  - Replication of temperature-sensitive mutants of alfalfa mosaic virus in
      protoplasts.
AB  - Six mutants of alfalfa mosaic virus (AIMV), previously found to have
      conditionally lethal defects when inoculated to tobacco leaf discs, were assayed
      for a temperature-sensitive (ts) phenotype in cowpea protoplasts. At 30 degrees
      the virus production of four mutants was less than 10% of that obtained at 25
      degrees , whereas wild-type AIMV multiplied with similar efficiencies at both
      temperatures. Supplementation experiments performed in protoplasts with two
      mutants indicated the presence of mutations on both RNA 1 and RNA 2. Viral plus-
      and minus-strand RNA synthesis induced by these mutants was monitored by the
      Northern blotting technique under various supplementation conditions. The ts
      defect was mainly in the production of viral minus-strand RNA whereas
      transcription of minus-strand into genomic and subgenomic RNAs was much less
      affected. In addition, results indicate that replication of RNA 1 requires a
      function not essential for the synthesis of the other RNAs. One of the mutants
      showed a host-dependent expression of ts mutations, probably reflecting that host
      viral interactions play an important role in A1MV replication.

PMID- 18638888
TI  - Time course of alfalfa mosaic virus RNA and coat protein synthesis in cowpea
      protoplasts.
AB  - A study was made of the time course of the synthesis of viral plus-strand RNA,
      minus-strand RNA, and coat protein in alfalfa mosaic virus-infected Cowpea
      protoplasts. The three genomic RNAs were synthesized at different rates, as were
      their corresponding minus-strands. We conclude that viral RNA synthesis is
      regulated both at the level of minus-strand production and the level of plus
      strand production. The synthesis of subgenomic RNA 4 was slower than that of its
      corresponding genomic RNA (RNA 3), indicating that an additional function,
      expressed later in infection, is required for production of subgenomic coat
      protein messenger. The data support a model for RNA 4 synthesis involving
      internal initiation by the RNA polymerase at the intercistronic junction in minus
      strand RNA 3. The temporal relationship of the synthesis of RNA 3, RNA 4, and
      coat protein is discussed.

PMID- 18638889
TI  - Detection and cell-free translation of subgenomic RNAs of tobacco etch virus.
AB  - RNA extracted from purified tobacco etch virus and virus-infected tissue was
      examined by the northern hybridization technique and found to contain several
      subgenomic-sized viral RNA species in addition to the 3 x 10(6) MW genomic RNA.
      Of the 10 subgenomic-sized RNAs detected (2.03, 1.24, 1.14, 1.01, 0.84, 0.62,
      0.55, 0.46, 0.34, and 0.28 x 10(6) MW), 4 were found in both virion RNA and
      infected tissue RNA, 3 others only in virion RNA, and 3 only in infected tissue
      RNA. Of the last three, two may be engendered during isolation by nuclease action
      on virion RNA, as indicated by controls. On the basis of their binding to
      oligo(dT) cellulose, all of the RNAs found in virus-infected tissue appeared to
      be polyadenylated. Cell-free translation of electrophoretically purified genome
      length TEV RNA in a rabbit reticulocyte system stimulated the synthesis of a
      39,000 MW polypeptide. In contrast, translation of unfractionated virion RNA in
      the reticulocyte system stimulated the production of a number of polypeptides;
      three of the principal products had molecular weights corresponding closely to
      those of known virus-encoded proteins. The predominant cell-free translation
      product of both electrophoretically purified genomic RNA and unfractionated
      virion RNA in the wheat germ system was a polypeptide with a molecular weight of
      41,000. These findings are discussed in relation to a translation strategy for
      tobacco etch virus involving selective transcription or processing of genomic RNA
      to generate subgenomic RNAs that are then translated.

PMID- 18638890
TI  - The cowpea mosaic virus RNA replication complex and the host-encoded RNA
      dependent RNA polymerase-template complex are functionally different.
AB  - Purification of the putative cowpea mosaic virus (CPMV) RNA replicase previously
      started with an RNA-dependent RNA polymerase activity which had been solubilized
      from a crude membrane fraction of CPMV-infected cowpea leaves by extraction with
      a Mg2+-deficient buffer. This led to the identification of a host-encoded,
      130,000-dalton monomeric enzyme, the activity of which was highly enhanced upon
      infection. As the role of this enzyme in viral replication was questionable, we
      reverted to the template-associated RNA-dependent RNA polymerase in the crude
      membrane fraction in order to characterize in detail its in vitro products. We
      now demonstrate that the crude membrane fraction of CPMV-infected cowpea leaves
      harbors two functionally different, RNA-dependent RNA polymerase activities that
      are both associated with endogenous template RNA and can be separated from each
      other without affecting their distinct properties. One of the RNA polymerase
      activities was specific for CPMV-infected leaves and constituted a CPMV RNA
      replication complex; enzyme activity in vitro allowed for the completion of
      nascent chains initiated in vivo. Full-length viral RNAS (B- and M-RNA) were
      produced which were recovered mainly in double-stranded form. Solution- and
      Northern blot hybridization demonstrated that the in vitro-labeled RNA chains
      were viral RNAs of positive polarity. The other template-associated RNA-dependent
      RNA polymerase activity occurred in both uninfected and infected leaves and
      transcribed in vitro endogenous plant and viral RNAs only into small RNAs (4-5 S)
      of negative polarity. Northern blot analysis revealed the RNA products of plant
      origin to be transcribed from two major RNA templates of approximately 0.26 and
      0.14 X 106 daltons, respectively. Washing of the crude membrane fraction in a
      Mg2+-deficient buffer did accomplish the complete release of the low-molecular
      weight RNA-synthesizing activity but did not solubilize the CPMV RNA replication
      complex. We tentatively conclude that the RNA-dependent RNA polymerase which has
      previously been purified from the buffer-soluble fraction and has been identified
      as a host-encoded enzyme is not involved in viral RNA replication. Solubilization
      of the viral replication complex was achieved with Triton X-100. By taking
      advantage of the characteristic conformation of the replication complex, we
      applied Sepharose 2B chromatography as a highly efficient and simple means for
      purifying the detergent-solubilized complex. We anticipate that this purification
      step should also be applicable to replication complexes of other RNA viruses.

PMID- 18638891
TI  - Use of micrococcal nuclease in the purification of highly template dependent RNA
      dependent RNA polymerase from brome mosaic virus-infected barley.
AB  - The template dependence of RNA-dependent RNA polymerase from brome mosaic virus
      (BMV)-infected barley was greatly increased by micrococcal nuclease digestion of
      the endogenous RNA. [32P]UMP incorporation by the nuclease-treated enzyme was
      stimulated 20-fold when BMV RNA was added as template, while incorporation by the
      untreated enzyme was stimulated only 5-fold by the addition of BMV RNA. Other
      properties of BMV polymerase were not changed significantly by nuclease
      digestion. The extract remained highly active and template specific. Analysis of
      the products of the reaction showed that separated BMV RNA components could be
      replicated independently to yield full-length replicative-form RNAs. These data
      provide strong evidence that the extract is capable of initiating RNA synthesis
      and that it includes the intact viral replicase. This method should be of general
      use, allowing the study of cell-free replication of any viral nucleic acid
      without requiring purification or solubilization of the replicase.

PMID- 18638892
TI  - The neurosurgical workforce in Australia and New Zealand What is the right number
      of neurosurgeons?

PMID- 18638893
TI  - Neuroimaging in epilepsy surgery: a review.
AB  - In recent years there has been a shift away from invasive monitoring, with more
      emphasis on the role of neuroimaging, in the selection of patients for epilepsy
      surgery. Although video-EEG is essential to confirm the diagnosis, and to
      determine the ictal onset, neuroimaging, in particular magnetic resonance imaging
      (MRI), forms the basis for selection of most surgical candidates. MRI, using
      visual analysis, is able to detect hippocampal sclerosis, the most common cause
      of temporal lobe epilepsy, in the majority of patients with this condition, with
      quantitative MRI increasing the sensitivity of this imaging technique. Other
      lesions readily detected on MRI include dysplasia, neuronal migration disorders
      and cavernomas. Studies have shown that the best postoperative results are
      achieved in patients with a lesion visible on MRI. Functional imaging, both
      single photon emission computed tomography (SPECT), in particular ictal SPECT,
      and photon emission tomography (PET), are important ancillary investigations
      providing valuable corroborative evidence of a seizure focus.

PMID- 18638894
TI  - The E. Graeme Robertson lecture concerning a very noble lady of a most curious
      shape.

PMID- 18638895
TI  - The neurosurgery workforce in Australia and New Zealand: a report.
AB  - The most recent review of the neurosurgical workforce in Australasia was produced
      in 1992. Regular update of statistics is necessary, particularly in response to
      recent political trends. A survey of all neurosurgeons both resident in
      Australasia and overseas was undertaken. The questionnaire focussed on four main
      areas: surgeon distribution; workload; activity breakdown; and surgeon: patient
      ratio calculation. Most surgeons live in New South Wales and Victoria, as
      expected. Following the recommendation of the Neurosurgical Society of
      Australasia, Australia currently has correct numbers of surgeons, however
      individual states vary widely. There are few subspecialty neurosurgeons in
      Australasia and almost all devote the vast majority of their time to clinical
      work. General work force issues are examined including future requirements with
      respect to population changes.

PMID- 18638896
TI  - MRI and epilepsy surgery.

PMID- 18638897
TI  - A longitudinal of Parkinson's disease: clinical and neuropsychological correlates
      of dementia.
AB  - Neuropsychological assessments were performed in ninety-one de novo patients
      participating in the Sydney Multicentre Study of Parkinson's disease. Assessments
      were made at baseline and after 3 and 5 years. Performance at baseline and after
      5 years was compared with controls. At baseline 37% of patients whose symptoms of
      Parkinson's disease had begun after the age of 70 years were demented. This
      compared with a prevalence of dementia of 8.8% in patients whose symptoms had
      begun before the age of 70 years. By 5 years the prevalence of dementia in the
      two groups had risen to 62.3% and 17.3% respectively. The death rate was higher
      over the 5 year period in the demented patients. Demented patients had more
      symmetrical signs, higher disability and bradykinesia scores and more impairment
      of gait and balance at baseline than non-demented patients. The presence of
      dementia at baseline predicted a poor response to treatment. The dementia at
      baseline had features of a subcortical dementia. Subsequently, aphasia, apraxia
      and agnosia emerged, making the dementia indistinguishable from that of
      Alzheimer's disease. Patients with well preserved cognitive function at baseline
      had a good response to levodopa and were more likely to develop levodopa induced
      dyskinesia. These results show that the clinical features of Parkinson's disease
      and response to treatment are influenced by the age of onset of symptoms and by
      the presence of dementia.

PMID- 18638898
TI  - Primary brain tumours manifesting during pregnancy: presentation of six cases and
      a review of the literature.
AB  - We review six cases of primary brain tumours with an initial manifestation of
      symptoms during pregnancy. Three patients presented with epileptic seizures, two
      with progressive motor disturbance, and one with visual disturbance. Three
      patients were diagnosed as harbouring brain tumours at 20-25 weeks of pregnancy,
      while the remaining three were diagnosed at 36-38 weeks of pregnancy. The tumours
      consisted of three cerebral gliomas of various degrees of malignancy and one case
      each of cerebellar medulloblastoma, pituitary adenoma and convexity meningioma.
      Three patients safely underwent surgical removal of the tumours at 24-31 weeks of
      pregnancy without any adverse effects on the foetus and two received
      postoperative radiation therapy. In the remaining three patients, who ranged from
      36-38 weeks of pregnancy at diagnosis, neurosurgical intervention was deferred
      until after delivery. Some of the problems in the management of brain tumours
      during pregnancy are discussed.

PMID- 18638899
TI  - The surgical treatment of small deep intracranial ateriovenous malformations: a
      report of 85 cases.
AB  - A series of 85 patients having what are defined as small, deep intracranial
      arteriovenous malformations (AVMs) is analysed in terms of presentation,
      investigation, treatment and outcome. This group of patients is taken from a
      consecutive series of 306 patients with AVM treated over a 20 year period. The
      anatomical distribution was as follows: cerebral hemisphere 54 patients, basal
      ganglia and thalamus 6 patients, brain stem and cerebellum 19 patients and deep
      dural 6 patients. Haemorrhage, both subarachnoid and intraparenchymal, was the
      predominant mode of presentation (71 of 85 cases). Other presentations were with
      epilepsy (5 cases), headache only (4 cases), progressive focal deficit (1 case)
      and mixed (4 cases). The vast majority of patients (71 of 85, 83.5%) were treated
      surgically: 67 by surgery only, 3 by surgery following partial embolisation and
      one with focussed irradiation after subtotal excision. The overall outcome in
      this group at 1 month was 27 (38.0%) improved (largely due to haematoma removal),
      42 (59.2%) unchanged and 2 (2.8%) worse. One of the unchanged group died during
      the second month with pulmonary complications following prolonged impairment of
      consciousness. The two patients worse at 1 month (Gd I -> Gd II) returned to Gd I
      within 3 months. There were 3 patients treated non-surgically (2 by focussed
      irradiation and 1 by embolisation) while 11 patients were not treated because
      they declined treatment (3 cases), they died before treatment could be carried
      out (3 cases), or treatment was deemed inadvisable (5 cases). The results of
      surgical treatment in small deep AVMs are compared with those of other treatment
      modalities, in particular focussed irradiation. It is argued on the basis of
      these figures that surgery remains the best treatment for these lesions.

PMID- 18638900
TI  - Cerebral lymphomatoid granulomatosis.
AB  - Lymphomatoid granulomatosis (LG) is an uncommon lymphoproliferative disease
      characterised by angiocentric and angioinvasive cellular infiltrates. The lung is
      the usual primary site with secondary central nervous system (CNS) involvement in
      20% of cases. Primary cerebral LG is a rare but potentially treatable disease
      with protean manifestations. Diagnosis is problematical and may be delayed when
      extracerebral disease is absent or occult. Six cases of cerebral LG are
      presented, and the clinical features, laboratory investigations, neuroimaging and
      pathological findings are reviewed.

PMID- 18638902
TI  - Colour Doppler imaging as an aid to excision of an arteriovenous malformation.
AB  - Colour Doppler ultrasound was used to localise an arteriovenous malformation
      (AVM) and its major feeding vessel intraoperatively. The successful ligation and
      division of this vessel could be confirmed with confidence on colour Doppler
      ultrasound. The malformation immediately became less turgid and was completely
      excised. Colour Doppler ultrasound was a valuable adjunct in the localisation and
      excision of this AVM and has application to AVM surgery in general.

PMID- 18638901
TI  - The great deceiver: the role of convulsive syncope in the history of epilepsy.
AB  - Because of its high medical and social profile, epilepsy has a voluminous
      documented history. For centuries it has been the subject of much speculation and
      attempted explanation. Even from antiquity examples taken from every day life
      have been used to explore, by analogy, the mechanism of epileptic seizures; and
      the convulsive phenomena of acute exsanguination have attracted much attention
      for this reason. A survey of the aspects and the consequences of this exercise in
      the study of seizure mechanisms shows that, until Jackson and Gowers emphasised
      the central role of the cortex in human epilepsy, a very complex schema had been
      constructed to explain epilepsy. This had been based upon erroneous information
      obtained by analogy from the convulsive phenomena of syncope and exsanguination.
      Over the millennia this mistaken concept served to divert scientific endeavour in
      attempts to explain and unravel the bases of epilepsy. It was only little more
      than a century ago that this concept was finally abandoned.

PMID- 18638903
TI  - Clinical implications of computer assisted surgical design in a carotid cave
      aneurysm.
AB  - In this report we demonstrate the application of computer assisted geometric
      design in the surgery of a carotid cave aneurysm. The method and basic concepts
      have been previously reported.(1) In this case report we referred to the
      previously published atlas of clinical images to input anatomical data. This
      enabled us to demonstrate and adequately identify microneurostructures for
      surgical simulation. The concepts and basic methods of computer assisted
      geometric design of microneurostructures are described.

PMID- 18638904
TI  - The expression of antisense vascular endothelial growth factor (VEGF) sequences
      inhibits intracranial C6 glioma growth in vivo by suppressing tumour
      angiogenesis.
AB  - Human gliomas, including astrocytomas, consist of highly heterogeneous
      populations of cells that represent different stages of malignancy. Glioblastoma
      multiforme is the most highly vascularised class of solid tumour. In order to
      develop efficacious adjuvant therapies for gliomas the growth pathway(s) targeted
      must be common to all of these tumours. As angiogenesis is a requirement for all
      solid tumour growth, we have targeted this process in order to suppress glioma
      growth in vivo. We have applied antisense VEGF gene expression to disrupt the
      VEGF/VEGF receptor paracrine pathway in C6 glioma cells and, thereby, inhibit
      tumour angiogenesis. C6 glioma cells which constitutively express antisense VEGF
      sequences were demonstrated to have significantly inhibited growth rates when
      implanted intracranially. Antisense VEGF expressing tumours had a markedly lower
      level of vascularisation which was accompanied by an increased level of necrosis
      compared to control tumours. Furthermore, these data support the notion that VEGF
      is the sole factor required for tumour angiogenesis as other potentially
      angiogenic factors could not compensate for the reduced level of VEGF expression
      in the antisense-VEGF expressing tumours. Our findings also suggest that the
      inhibition of angiogenesis is sufficient to significantly suppress tumour growth
      and is thus an effective point for therapeutic intervention for gliomas and all
      solid tumours.

PMID- 18638905
TI  - Approach to dorsal pontine lesions via the fourth ventricle with SSEP monitoring:
      a report of two cases.
AB  - Operative morbidity is a limiting factor for the trans-fourth ventricular
      approach to brain stem lesions. The usefulness of somatosensory evoked potentials
      (SSEP) in this approach has not been established. Two patients with pontine
      lesions were operated on with SSEP monitoring using the trans-fourth ventricular
      approach. One patient had a cavernous haemangioma and the other had a chordoma
      invading the pons. SSEP remained normal in the first, and a slight transitory
      decrease of the amplitude was observed in the second patient. The lesions were
      macroscopically totally removed with minimal postoperative neurological
      deterioration. In this approach it is assumed that SSEP monitoring was especially
      helpful for removal of the lesions extending deeply in the pons.

PMID- 18638906
TI  - Kissing neurinomas of the vestibular and vagal nerves.
AB  - We report the clinical and neuroimaging features of a patient with double
      schwannomas originating from the vagal and vestibular nerves. Such an association
      seemed unique, and its surgical implications are discussed.

PMID- 18638907
TI  - Giant intracranial varix arising from an arteriovenous fistula.
AB  - A case of a giant intracranial varix arising from an arteriovenous (AV) fistula
      is reported. This 16 year old boy presented with a sudden onset of headache and
      dizziness. The patient had suffered from intermittent seizure attacks since the
      age of 4. Brain computed tomography (CT), taken 2 years prior to admission,
      showed compression of the quadrigeminal plate by a suspicious mass lesion. His
      brain CT, magnetic resonance imaging (MRI), and cerebral angiography on admission
      demonstrated a giant varix with evidence of haemorrhage in the cerebellum. The
      varix was fed from branches of the posterior cerebral artery and drained through
      a dilated vein into the vein of Galen. It was resected surgically. Surgery and/or
      endovascular obliteration of the AV fistula is required because the varix which
      develops from an AV fistula can enlarge and rupture.

PMID- 18638908
TI  - Exercise intolerance in Kearns-Sayre syndrome.
AB  - Exercise intolerance is a common finding in mitochondrial diseases, including
      Kearns-Sayre syndrome (KSS), characterised by progressive external
      ophthalmoplegia, cardiac conduction defects and atypical pigmentary degeneration
      of the retina. Exercise studies were performed in a 32 year old woman with KSS
      who had received an atrio-ventricular sequential pacemaker because of continuing
      breathlessness, having presented with complete heart block requiring a fixed rate
      demand pacemaker 6 years earlier. Minute ventilation, oxygen consumption, and
      carbon dioxide production were measured at different workloads on 3 consecutive
      days by collecting expired air. Compared to controls, after exercise at a
      subanaerobic workload, heart rate and ventilation were exaggerated relative to
      both oxygen consumption and carbon dioxide production. The findings are
      consistent with the hypothesis that, in mitochondrial disorders, impaired
      oxidative phosphorylation leads to uncoupling of cardiac ouput and ventilation
      relative to muscle metabolic rate.

PMID- 18638909
TI  - Consciousness.

PMID- 18638910
TI  - Scientific meeting of the Australian association of nuerologists.

PMID- 18638911
TI  - High resolution two-dimensional gel electrophoresis of structural proteins of
      baculoviruses of Autographa californica and Porthetria (lymantria) dispar.
AB  - The structural polypeptides of baculoviruses of Autographa californica (AcMNPV)
      and Porthetria dispar (PdMNPV) were analyzed by two-dimensional (2-D) gel
      electrophoresis. Purified proteins were solubilized in urea-NP40 mix and
      separated by isoelectric focusing in the first dimension; electrophoresis in the
      presence of sodium dodecyl sulfate (SDS) separated proteins by molecular weight
      in the second dimension. Eighty-one acidic polypeptides ranging in molecular
      weight from 13,500 to 86,000 Da were resolved in AcMNPV enveloped virions. The
      predominant polypeptide had a molecular weight of 41,500 and was considered to be
      the major capsid protein. Nucleocapsids from AcMNPV were resolved into 64
      polypeptides. At least 11 of the polypeptides, including most of the high
      molecular weight proteins, that were not resolved in nucleocapsids were
      considered to be envelope proteins. For PdMNPV enveloped virions, there were 95
      acidic polypeptides ranging in molecular weight from 13,500 to 85,500. The
      predominant polypeptide had a molecular weight of 46,500 Da. Polyhedral proteins
      (polyhedrin) isolated from protease-inactivated polyhedra and separable into a
      single major polypeptide (approx. 31,000) on one-dimensional SDS-polyacrylamide
      gel electrophoresis were resolved into six polypeptides for both viruses. All six
      polyhedrin polypeptides had the same molecular weight, but their isoelectric
      points ranged from pH 5.3 to 5.9 for AcMNPV and from pH 5.7 to 6.2 for PdMNPV.
      These six polypeptides were also detected when protease-inactivated or
      noninactivated whole polyhedra were analyzed directly by 2-D electrophoresis. It
      is assumed that not all the observed baculovirus polypeptides were unique
      species. Some proteins, especially the polyhedrin polypeptides, appeared to be
      related and had altered mobilities as a consequence of post-translational
      modifications.

PMID- 18638912
TI  - Serological analysis of 17 baculoviruses from subgroups A and B using protein
      blot immunoassay.
AB  - We used the protein blot radioimmunoassay technique (Smith and Summers, 1981) to
      evaluate the immunoreactivity of antisera made against SDS-disrupted baculovirus
      structural proteins. Eight antisera (six for NPVs and two for GVs) were tested
      against eleven nuclear polyhedrosis (NPV) and six granulosis viruses (GV).
      Homologous reactions revealed that SDS-disrupted baculovirus antigens elicited
      antibodies which reacted with several of the virus proteins. Heterologous
      reactions of each viral antiserum were determined with a total of 17
      baculoviruses. Using these data and that of Smith and Summers (1981), we were
      able to detect a number of shared antigenic determinants which revealed some
      specific serological relationships among some of the 17 viruses tested. The MNPVs
      showing distinct serological relatedness included those of Autographa
      californica, Rachiplusia ou, Anticarsia gemmatalis, Choristoneura fumiferana, and
      Orgyia pseudotsugata. Heliothis armiger MNPV and Heliothis zea SNPV shared cross
      reacting antigenic determinants as did Trichoplusia ni SNPV, Pseudoplusia
      includens SNPV, and Heliothis zea SNPV. The GVs. of T. ni, H. armiger, and
      Spodoptera frugiperda were also serologically related. Also reactions were
      detected which indicated the presence of common antigenic determinants among
      different baculovirus subgroups in addition to those originally detected in our
      earlier study (Smith and Summers, 1981). Because of the large number of
      structural proteins in baculoviruses and the lack of information concerning their
      structural or functional roles in the virus group specific antigenic determinants
      could not be identified. However, protein blot RIA allows specific identification
      of baculoviruses and the number and molecular weight of homologous and
      heterologous proteins sharing antigenic determinants.

PMID- 18638913
TI  - Helper components of two potyviruses are serologically distinct.
AB  - The specificity of antisera to helper component (HC) from tobacco vein mottling
      virus (TVMV)- or potato virus Y (PVY)-infected tobacco plants was tested in
      immunoprecipitation and immunoabsorption chromatography experiments. Treatment
      with the homologous antiserum abolished or drastically reduced the activity of
      either TVMV-HC or PVY-HC, as measured by their ability to effect aphid
      transmission of purified tobacco etch virus, while the heterologous antiserum had
      little or no effect on HC activity. Loss of TVMV-HC and PVY-HC activity in the
      immunoabsorption chromatography experiments was associated with the removal of a
      53- and a 58-kDa polypeptide, respectively. The results indicate that
      serologically distinct HC proteins are produced in response to specific potyvirus
      infection and suggest that HC is virus coded.

PMID- 18638914
TI  - Thrombolysis for acute stroke.

PMID- 18638915
TI  - Magnetic stimulation of the motor cortex: Clinical applications.
AB  - Transcranial magnetic cortical stimulation provides the clinical
      neurophysiologist with a method to examine alterations in the function of central
      motor pathways in diseases affecting the motor system. The technique has great
      research potential and has led to increased understanding of intracortical
      physiology, corticospinal tract function, motor system plasticity and motor
      control. Subclinical cerebral and spinal cord lesions may be demonstrated, and
      the technique has a potential role for quantification and monitoring of disease
      progression, and for early prognostication after stroke. Intraoperative
      monitoring of motor evoked potentials (MEP) is of value during spinal cord
      surgery, but due to attenuation of magnetic MEPs during anaesthesia, transcranial
      electrical stimulation is more appropriate for intraoperative recordings.

PMID- 18638916
TI  - Progress in head injury management.
AB  - Preventable secondary injury remains disturbingly common and can only be reduced
      by highly organized and integrated services, and careful and continuous
      monitoring. Continuous non- or relatively non-invasive bedside monitoring of
      factors closely related to brain metabolism and function is becoming a practical
      reality. To the extent that the complex changes initiated by traumatic brain
      injury are 'processes' rather than 'events' it may become possible for components
      of injury to be halted or reversed. Pharmacological therapy given early after
      injury may be able to reduce the harmful events initiated by the injury. Head
      injury management is multidisciplinary. Improvements in head injury outcome have
      come about through better organisation of services - efficient retrieval, early
      investigation and removal of clots, and management in experienced intensive care
      units. Australian neurosurgeons have played a leading role in defining standards
      of care, in organizing services and in raising public health issues related to
      head injury. With the increasing and necessary involvement of other specialists
      and the greater dependence on technically demanding intensive monitoring and
      medical management, it is important that neurosurgeons remain at the forefront of
      the care of patients with head injury and not simply be reduced to managing the
      surgical complications on request.(86).

PMID- 18638917
TI  - Grading of gliomas.
AB  - The traditional schemes for grading gliomas, in particular astrocytomas, have not
      been widely accepted by the neuropathology community. At present, four systems
      are in use, separating either three or four grades of tumour. All four systems
      are histopathology-based. Intermediate grade astrocytomas show a wide variation
      in survival times and prediction based on histopathological features remains
      problematic. Molecular-genetic alterations that have been identified in
      astrocytomas will eventually be incorporated into grading schemes as indicators
      of where a tumour has reached in the biological continuum from low to high grade
      of malignancy.

PMID- 18638918
TI  - Transcranial cortical stimulation in disorders of the central motor pathways.
AB  - Motor evoked potentials (MEPs) were studied in 63 patients with disorders
      affecting central motor pathways. These were classified into five subgroups:
      motor neuron disease (16), multiple sclerosis (13), cerebral infarction (19),
      spinal cord lesions (10) and hereditary spastic paraplegia (5). Three patients
      with hysterical paraplegia were also studied. Results were compared to those
      obtained from 30 normal subjects. In normal subjects the mean central motor
      conduction time (CMCT) was 6.4 ms (range 3.4-8.1 ms, SD 1.0 ms) for abductor
      digiti minimi and 13.2 ms (range 9.7-17.0 ms, SD 2.3 ms) for tibialis anterior.
      Amplitude of the cortical MEPs was defined as a percentage of the size of the
      peripheral compound muscle action potential (CMAP) and ranged from 14 to 85%.
      Fifteen of 16 patients with motor neuron disease and all patients with cerebral
      infarction, multiple sclerosis (MS), spastic paraparesis and non-MS spinal
      lesions had abnormal studies including low amplitude, dispersed or absent
      responses and prolonged CMCTs. Patients with MS had markedly prolonged CMCTs. In
      three cases of hysterical weakness MEPs were within normal limits. MEPs are a
      useful method to detect pathology in the central motor pathways and may have a
      significant role in the diagnosis of disorders involving the upper motor neuron.

PMID- 18638919
TI  - Epilepsy and brain abscess.
AB  - Although epilepsy is a well recognized complication of brain abscess, the true
      incidence of seizures and the factors which predispose to seizure occurrence and
      recurrence are not well established. This study retrospectively assessed the
      incidence of seizures and seizure recurrence in 35 consecutive adult patients
      diagnosed surgically with brain abscess between 1984 and 1994. Following
      diagnosis, all patients were treated with phenytoin. There was no relationship
      between the site of the abscess, organism cultured, surgical treatment, presumed
      aetiology, age or sex of the patient and seizure occurrence. It is concluded that
      epilepsy is a common complication of cerebral abscess, frequently occurring at
      presentation. Early seizures predispose to late seizures and in these patients
      long-term anticonvulsant treatment should be considered. If a patient remains
      seizure free at discharge, the chance of developing seizures is relatively small.

PMID- 18638920
TI  - Management of minor head injury: the value of early computed tomography and serum
      protein S-100 measurements.
AB  - Computed tomography (CT) scan was performed within 6 h in 91 patients with minor
      head injury (MHI). Eight patients (9%) demonstrated intracranial lesions on CT
      scan (6 brain contusions, 1 brain edema and 1 extradural hematoma). No patient
      required craniotomy. In patients with normal CT scan, no complications to the
      head injury were observed. Patients with intracranial lesions were hospitalized
      significantly longer (mean 9.4 days) than patients without (mean 1.6 days). In a
      subgroup of 50 patients with normal CT scan, serum S-100 protein was measured on
      admission. Elevated S-100 levels were seen in 10 of 50 patients (0.5-2.4 mug/L,
      mean 1.1). These patients were hospitalized significantly longer (mean 3.4 days)
      compared to patients with normal CT scan and normal S-100 levels (mean 1.1 days).
      MHI patients with GCS 14-15 without neurological deficits can safely be
      discharged when CT scan is normal. Serum protein S-100 measurements appear to
      provide information about diffuse brain injury after MHI.

PMID- 18638921
TI  - Vertex extradural haematomas: a report of 3 cases and a review of the literature.
AB  - Extradural haematomas occurring at the vertex are an unusual group of a common
      condition. Their clinical presentation is frequently atypical and the diagnosis
      often delayed. The clinical findings do not always correlate with the site of the
      lesion and venous engorgement due to impaired venous drainage is the likely
      explanation. Nearly all cases will have a fracture crossing the vertex but this
      may go undetected as skull X-rays are frequently not performed in acute trauma
      and the vertex is a difficult area to visualize with conventional axial computed
      tomography (CT) scanning. Magnetic resonance image (MRI) scanning is the
      investigation of choice but is rarely available in acute trauma. Patients may
      present in an acute, subacute or chronic fashion. The treatment can be surgical
      or non-surgical depending on the neurological condition of the patient. Most
      patients make an excellent recovery.

PMID- 18638922
TI  - Surgical management of vertebrobasilar aneurysms.
AB  - This paper reports a retrospective analysis of 50 patients who had 55 posterior
      circulation aneurysms treated surgically. Twenty-four patients presented with
      subarachnoid haemorrhage. Thirty-three of the lesions involved the basilar
      artery, predominantly at its bifurcation. There were 13 giant aneurysms in the
      series, 3 false aneurysms, 1 mycotic aneurysm and 3 associated with arteriovenous
      malformations. Forty-nine aneurysms (89%) were able to be treated surgically and
      38 (69%) of these were directly clipped. Neurological assessment at discharge
      indicated that 38 patients (76%) had a good outcome. Moderate disability occurred
      in 7 patients (14%). Four patients (8%) were left severely disabled or
      vegetative. There was a single death in the series (2%).

PMID- 18638923
TI  - Can the interictal EEG predict successful temporal lobectomy for epilepsy?
AB  - Scalp and sphenoidal electroencephalograms (EEGs) were examined retrospectively
      from 45 patients who had temporal lobe surgery for epilepsy in a Comprehensive
      Epilepsy Programme. Interictal EEG patterns were divided into 4 groups: group 1
      (18 patients) showed phase reversal of sharp (8) or spike (10) waves about one
      sphenoidal electrode, group 2 (11 patients) showed unilateral sharp, spike or
      wave activity in scalp leads only; group 3 (8 patients) showed bilateral
      abnormalities which were 60%; lateralized and group 4 (8 patients) showed non
      lateralized changes. Lateralized EEG patterns predicted the side of subsequent
      surgery in all 37 cases. All 18 patients in group 1 benefited from surgery (10
      seizure free at 1 year) while 20 of 27 patients in the other 3 groups benefited
      (13 seizure free). These results favour group 1 (P < 0.05). By comparison, the
      magnetic resonance image scan predicted the side of surgery in 23 of 36 (64%)
      patients and single photon emission tomograph scans predicted the side of surgery
      in 11 of 24 (46%) patients who had ictal and interictal isotope injections. Focal
      sphenoidal electrode discharges predict successful temporal lobectomy for
      surgery.

PMID- 18638924
TI  - A murine model of communicating hydrocephalus: Role of TGF-beta1.
AB  - Subarachnoid haemorrhage (SAH) often causes communicating hydrocephalus. We
      recently found that intrathecal injection of human recombinant transforming
      growth factor (hrTGF)-beta1 induced communicating hydrocephalus in mice. In this
      experiment we examined whether hydrocephalus could be generated in mice by
      intrathecal injection of autologous serum, which would contain TGF-beta1 in a
      similar situation to SAH. Mouse serum, plasma and a range of quantities of hrTGF
      beta1 were injected intrathecally into 10 day old C57BL/6 mice. The sizes of the
      lateral ventricles were measured some weeks after injection. The serum induced
      hydrocephalus which was prevented by additional injection of anti-TGF-beta1
      antibody. Immunoblot analysis showed a band of the active form of TGF-beta1 in
      the serum which was not detected in the plasma. This study therefore suggests
      that active TGF-beta1 in cerebrospinal fluid after SAH contributes to the
      generation of communicating hydrocephalus.

PMID- 18638925
TI  - Differentiation inducing effects of vesnarinone on human glioma cells.
AB  - The effects of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)
      quinolinone (vesnarinone) on the growth of glioma cells were examined in vitro.
      Vesnarinone at a dose of 100 mug/ml suppressed the growth of four different
      glioma cell lines, U-251MG, U-373MG, U-87MG and A-172, by approximately 50%, with
      an elongation of the cytoplasmic process on day 5 of culture. The long-term
      culture of U-87MG with 10 mug/ml of vesnarinone was continued up to day 34.
      Although growth suppression was approximately 25% on day 5, it reached over 95%
      on day 34. An increase in the cyclic adenosine monophosphate content of glioma
      cells cultured with vesnarinone was observed by enzyme-linked immunosorbent assay
      (ELISA). The accumulation of glial fibrillary acidic protein was observed to
      occur with vesnarinone by ELISA. These findings suggest that vesnarinone
      suppressed the growth and induced differentiation of glioma cells in vitro.

PMID- 18638926
TI  - Prolactin secreting pituitary tumours with marked visual field impairment should
      be treated by bromocriptine.

PMID- 18638927
TI  - Management of a prolactin macroadenoma with visual loss: Indications for surgery.

PMID- 18638928
TI  - Prolactin secreting pituitary tumours with marked visual field impairment should
      be treated by early surgical decompression versus treatment by bromocriptine.

PMID- 18638929
TI  - Cavernous angioma of the cerebellopontine angle.
AB  - Cavernous angiomas are vascular malformations that are seldom found in the
      cerebellopontine angle or in the internal auditory canal. We report the case of a
      51-year-old man suffering from a rapidly progressive hearing loss, tinnitus and
      minor unsteadiness. Neurootological examination showed a canal paresis of 91% on
      the right side. The subsequent neuroradiological examination with magnetic
      resonance imaging revealed a tumour of the cerebellopontine angle with
      intracanalicular extension. The observed intensities on T1-, T2- and gadolinium
      enhanced sequences suggested the diagnosis of a vestibular schwannoma.
      Intraoperatively, a reddish tumour was found and histological examination
      revealed a cavernous angioma. Even though extensive diagnostic procedures were
      performed, the correct diagnosis could not be established preoperatively.

PMID- 18638930
TI  - Pathophysiology of congenital mirror movements.
AB  - A case of congenital mirror movements occurring in association with mild
      hemiparesis and unilateral schizencephaly was investigated using focal
      transcranial magnetic stimulation. The cortical motor representations for first
      dorsal interosseous, abductor digiti minimi and biceps brachii were mapped for
      both cerebral hemispheres: bilateral short latency EMG responses were elicited
      with stimulation over the nonschizencephalic hemisphere while no short latency
      responses were obtained with stimulation over the schizencephalic hemisphere. The
      cortical representations for all three homologous muscle pairs studied were
      colocalized, and the responses occurred at identical latencies bilaterally. Our
      findings, plus previous observations suggesting a single functional motor cortex
      in schizencephaly, are consistent with the suggestion that mirror movements are
      the result of branched corticospinal projections to distal muscle groups.

PMID- 18638931
TI  - Hashimoto's encephalopathy.
AB  - We describe a 59-year-old female with Hashimoto's encephalopathy whose
      presentation was characterized by a subacute onset of confusion, depressed level
      of consciousness, tremor and pyramidal signs. She was euthyroid on presentation
      but antithyroid antibodies were elevated. Hashimoto's thyroiditis was confirmed
      by thyroid biopsy. There was a spontaneous remission of the neurological
      disorder. Subacute encephalopathy is often investigated with thyroid function
      tests only. In cases of unexplained encephalopathy, thyroid antibodies and/or
      thyroid biopsy should be performed to exclude this condition.

PMID- 18638932
TI  - Recovery from multiple brain infarcts complicating basilar artery dissection.
AB  - A 38-year-old woman suffered a spontaneous basilar artery dissection leading to
      bilateral occipital, right thalamic and cerebellar infarction and a dorsal
      midbrain syndrome. Computerized tomography showed left cerebellar, right thalamic
      and bilateral occipital infarctions and selective angiography showed a narrowed
      segment in the basilar artery, absent filling of the right superior cerebellar
      artery and narrowing of the right posterior cerebral artery. She improved rapidly
      without specific therapy and made a near full recovery. Basilar artery
      dissection, while often fatal, may have a benign outcome and we review the
      literature in this regard.

PMID- 18638933
TI  - A reconstruction method of cerebral surface anatomical images for image guided
      localization.
AB  - We have developed a simple and practical method to reconstruct cerebral surface
      anatomical images for better presurgical planning and surgical orientation with
      the aid of a personal computer. The area representing the cortical surface was
      selected from the most superficial slice of the T1-weighted magnetic resonance
      (MR) images. The selected area was then overlaid upon the next superficial slice
      and the alignment adjusted. By repeating this procedure four to seven times we
      obtained a brain surface image which clearly displayed gyri and sulci. With the
      same method images of the vascular components of the cerebral surface were
      obtained from the T2-weighted images or MR angiograms. The brain surface and the
      vascular images were then combined to reconstruct a surface anatomical image
      (SAI). In addition, the outline of the lesion and natural landmarks, such as
      ventricles, were added if necessary. Compared to conventional surface anatomy
      scanning (SAS) or three-dimensional image reconstruction procedures, our method
      has the advantage of displaying, within a reasonable time, the manifest cortical
      surface from the direction of the planned surgical approach. The SAIs obtained
      for individual patients have proven to be useful for presurgical planning and
      minimizing surgical damage to the eloquent cortex in approaching both surface and
      subcortical lesions.

PMID- 18638934
TI  - A safer technique for clipping of thin walled and broad based cerebral aneurysms
      after wrapping.
AB  - A simple and safe method for clipping of small, broad-based and thin-walled
      aneurysms is described. Premature rupture during clipping and slip-out of the
      applied clip are frustrating and disastrous phenomena often encountered during
      surgery of these aneurysms. Clipping such aneurysms after they have been wrapped
      with a piece of cotton gauze is a safe and effective method to prevent premature
      rupture and slip-out of the clip. The authors report their experience and
      operative results of 12 patients treated with this technique.

PMID- 18638935
TI  - Anatomical location of carotid cave aneurysms.
AB  - Seven carotid cave aneurysms were studied with various imaging techniques and at
      surgery. The carotid cave aneurysm projects medially with most of it overlying
      the sella turcica. The aneurysm partially overlies the anterior loop of the
      cavernous carotid artery and the anterior loop always partially overlies the
      sella turcica in these cases. The site of the cave aneurysm corresponds well with
      an area of the carotid artery observed on dissection studies which is adjacent to
      the sella. This parasellar area differs from the carotid cave in that it is below
      the dural ring and is not reinforced by the bone of the carotid sulcus. The
      findings explain the medial projection of the cave aneurysm in that this is the
      direction of least resistance which in turn also corresponds with the site of
      maximal force of the flowing blood.

PMID- 18638936
TI  - Growth cycle of a virus, PBCV-1, that infects Chlorella-like algae.
AB  - The growth and purification of milligram quantities of a large double-stranded
      DNA virus, PBCV-1, which replicates in a Chlorella-like alga is described. The
      virus had an adsorption rate constant of ca. 5 x 10(-9) ml/min, a latent period
      of 150 to 180 min, and a burst size of 200 to 350 PFUs when the host was actively
      growing in the light. The eclipse period was 30 to 50 min shorter than the latent
      period. PBCV-1 also replicated in dark grown Chlorella but the burst size was
      reduced ca. 50%. The photosynthetic inhibitor, 3-(3,4-dichlorophenyl)-1,1
      dimethylurea, had no effect on viral replication. Thus viral replication does not
      require host photosynthesis. Viral infection rapidly inhibited both growth and
      CO2 fixation of the host Chlorella.

PMID- 18638937
TI  - A mutant of alfalfa mosaic virus with an unusual structure.
AB  - A spontaneous mutant of alfalfa mosaic virus (AMV) with an altered structure is
      described. By analysis of pseudorecombinants the mutation(s) responsible for the
      altered structure were assigned to RNA 3. By in vitro translation and serology it
      is shown that both proteins (35K protein and coat protein) encoded by RNA 3 are
      changed. The mutation(s) present in RNA 3 also have an effect on the ratio of the
      three genomic RNAs, both in virion as well as in double-stranded RNA
      preparations. Compared to wild-type particles mutant particles (1) have a lower
      electrophoretic mobility in polyacrylamide gels, (2) have a greater sedimentation
      velocity in sucrose density gradients, (3) do contain the same percentage of RNA,
      (4) are more prone to aggregation, (5) are somewhat less stable during storage,
      and (6) are less sensitive to uncoating by AMV-RNA. Electron micrographs show
      that the mutant preparations contain some very long bacilliform particles,
      however the majority of the particles is spheroidal and bear a strong resemblance
      to the particles of the ilarviruses. The structural properties of this mutant
      support the classification of AMV as an ilarvirus.

PMID- 18638938
TI  - The self-assembly of the cowpea strain of southern bean mosaic virus: formation
      of T = 1 and T = 3 nucleoprotein particles.
AB  - Virion-like particles of the cowpea strain of southern bean mosaic virus were
      assembled from isolated coat protein and RNA components in vitro at low ionic
      strength. Purified southern bean mosaic virus RNA was heterogeneous on sucrose
      gradients, and was separated into low (0.3 - 0.6 x 10(6) Da) and high (1.0-1.4 x
      10(6) Da) molecular weight (MW) fractions. Assembly with high MW RNA resulted in
      T = 3 particles at pH 7 and 9. Low MW RNA assembled with coat protein into T = 1
      particles at pH 5 and 7, and into T = 3 particles at pH 9. The formation of T = 3
      particles at pH 9, and of T = 1 particles at pH 7, required the presence of Ca2+
      and Mg2+ ions. Proteolytic digestion of the basic amino-terminal arm of the coat
      protein in the absence of RNA indicated that the arm-RNA interaction is an early
      event in the assembly of an initiation complex for both types of particles. The
      effects of pH and divalent cations on SBMV assembly suggest that the charge
      configuration of carboxyl group clusters in the putative initiation complex
      regulates further subunit interactions and, hence, the mode (T = 3 vs T = 1) of
      assembly.

PMID- 18638939
TI  - A temperature-sensitive mutant of the baculovirus Autographa californica nuclear
      polyhedrosis virus defective in an early function required for further gene
      expression.
AB  - Fifteen temperature-sensitive (ts) mutants of the baculovirus Autographa
      californica nuclear polyhedrosis virus (AcNPV) have been analyzed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of proteins
      synthesized in infected cells. One of the mutants, tsB821, was found to be
      defective in a very early function. Seven virus-induced proteins were synthesized
      by 2 hr postinfection. In marked contrast to wild-type virus and the other 14 ts
      mutants, the synthesis of further virus-induced proteins did not occur in tsB821
      infected cells at the restrictive temperature (33 degrees ). Host protein
      synthesis continued as normal after transient expression of the seven early
      proteins. Viral-specific DNA synthesis was blocked or significantly delayed in
      tsB821-infected cells at 33 degrees . The relative synthesis of certain viral
      induced proteins, particularly P31, P32, P42, P66, and P69, varied considerably
      in the remaining 14 mutants at 33 degrees. Three mutants exhibited alterations in
      specific polypeptides; P75 was approximately 1 kDa smaller in tsB1075, P40 was
      approximately 1 kDa smaller in tsB951, and P25 was greatly reduced in quantity or
      altered in tsB305.

PMID- 18638940
TI  - Mapping early transcription products of Autographa californica nuclear
      polyhedrosis virus.
AB  - The regions of the AcMNPV genome represented as cytoplasmic transcripts early
      after infection of Spodoptera frugiperda cells prior to and encompassing the
      initiation of DNA replication were mapped. In vivo(32)P pulse-labeled cytoplasmic
      RNA from infected cells at various times postinfection was used to probe Southern
      blots of cloned EcoRI AcMNPV DNA fragments. At the earliest time point studied
      (0.5 - 2.5 hr p.i.) transcripts represented a large proportion of the genome
      although specific regions were predominantly transcribed (EcoRI A, C, F, J, O, Q,
      S, and T). After the onset of viral DNA synthesis predominant cytoplasmic
      transcripts represented more dispersed areas of the genome, particularly those
      regions which were only weakly transcribed earlier after infection. Genomic
      regions containing major late genes were not predominantly transcribed by 7.5 hr
      p.i.

PMID- 18638941
TI  - Can I trust you, doctor? The ethics of managed care.

PMID- 18638942
TI  - Experimental neuronal protection in cerebral ischaemia part I: experimental
      models and pathophysiological responses.
AB  - Development of neuroprotective strategies for the treatment of cerebral ischaemia
      depends upon knowledge of the pathophysiological responses which occur during the
      period of ischaemia and during reperfusion. Both in vitro and in vivo studies
      have been used to accumulate this base of knowledge; a brief examination of the
      results from the two approaches reveal that they are in general agreement and
      often provide complementary information. Ischaemia in the absence of reperfusion
      can lead to neuronal death from protein degradation and DNA breakup. Resupply of
      blood permits increased free radical attack but energy supply can still be
      limited as the cerebral circulation reacts to release of cicosanoids, and DNA
      repair utilizes ATP.

PMID- 18638943
TI  - The molecular genetics of astrocytomas: current understanding and future
      applications.
AB  - The prognosis for adult patients with astrocytomas remains poor. In recent years
      there has been a significant amount of research into the molecular mechanisms
      underlying the development and progression of these tumours. This review
      describes some of the oncogenes and tumour suppressor genes that are important in
      the development of astrocytoma, as well as the molecular mechanisms underlying
      angiogenesis and invasion. Possible clinical applications are described.

PMID- 18638944
TI  - Pathophysiological basis of cerebral vasospasm following aneurysmal subarachnoid
      haemorrhage.
AB  - Subarachnoid haemorrhage (SAH) following rupture of an intracranial aneurysm is
      associated with a greater than 35% mortality within the first 3 months. Delayed
      ischaemia due to cerebral vasospasm (CVSP) occurs in approximately one-third of
      all patients with this disease and accounts for over 20% of its overall morbidity
      and mortality. Although the clinical and experimental features of CVSP have been
      widely documented, the pathophysiology remains controversial. Its basis, however,
      is almost certainly multifactorial. The cerebrovascular microenvironment is
      significantly altered as a consequence of haemorrhage into the subarachnoid
      space. Important putative factors implicated in this change include
      oxyhaemoglobin, endothelin, oxygen- derived free radicals, and neurovascular
      nitric oxide, arachidonic acid and carbon monoxide systems. In addition, distinct
      histological changes related to the overall physiological response occur in
      cerebral vessels undergoing spasm. The present work aims to detail and unify our
      current understanding of the biological mechanisms underlying this devastating
      condition.

PMID- 18638945
TI  - Secondary insults to the injured brain.
AB  - While reversing established central nervous system damage is clearly a difficult
      task, preventing or limiting ongoing destructive processes in the brain may be a
      more achievable goal. The monitoring technology required to detect clinically
      significant adverse secondary events has evolved considerably in the past few
      years. As a result it has become evident that such adverse events are common in
      the head injured patient and that they can have a dramatic effect on outcome.
      Furthermore, it is also becoming clear that these secondary insults are, to a
      significant degree, preventable. It is likely that simple physiological
      maneuvers, such as maintaining the cerebral perfusion pressure, as well as newer
      pharmacological agents, will be useful for this purpose. The pathophysiology of
      brain swelling remains unclear and deserves continued study. This review
      describes the factors responsible for secondary brain injury, some practical ways
      of identifying and managing them, and certain newer pharmacological agents that
      may be valuable in the clinical setting.

PMID- 18638946
TI  - Selective versus non-selective temporal lobe surgery for epilepsy.
AB  - Over a 10-year period 100 temporal lobe operations were performed for non
      lesional temporal lobe epilepsy (TLE). Seventy-two patients had conventional
      anterior temporal lobectomy (ATL) and 28 had selective amygdalohippocampectomy
      (AH). Forty-three ATL patients (60%) became seizure free compared to 6 AH
      patients (21%) (P < 0.005). An unsatisfactory outcome was obtained in 11 (15%)
      ATL patients and 14 (50%) AH patients (P < 0.01). Fourteen AH patients
      subsequently had a second ATL procedure; 6 improved, 3 becoming seizure free.
      There were no differences between the two groups in the incidence of mesial
      temporal sclerosis (MTS) or normal pathology. However, ATL patients had a higher
      concordance rate of preoperative investigations which may have made them more
      favourable surgical candidates. It was concluded that ATL was more likely to
      produce a seizure free outcome than AH and should be used as the routine surgical
      procedure for temporal lobectomy. However, AH can give a satisfactory outcome and
      may be preferred when a patient has good verbal memory and all preoperative tests
      are concordant.

PMID- 18638947
TI  - Dysembryoplastic neuroepithelial tumour: the Western Australian experience.
AB  - Dysembryoplastic neuroepithelial tumour (DNET) is a rare tumour that is usually
      seen in the context of epilepsy surgery. The purpose of this study was to provide
      a profile of DNET in an unbiased population. The 2020 brain tumours diagnosed in
      Western Australia in the 10-year period 1982-1991 were reviewed; 5 cases of DNET
      were identified. All patients were neurologically intact and presented with
      complex partial seizures from a young age. Surgery was performed for tumour
      resection or biopsy in all cases; no patient underwent surgery specifically for
      epilepsy control. The lesions were intracortical, multinodular and were composed
      of astrocytes, oligodendrocytes and neurons. Three patients underwent total or
      subtotal resection and their seizures were either abolished or reduced in
      frequency. Two patients had biopsies only and were clinically unchanged. There
      has been no evidence of recurrence in up to 8 years' follow-up. The diagnosis of
      DNET is important because it is a surgically treatable benign tumour.

PMID- 18638948
TI  - Stereotactic intracavitary irradiation of large cystic craniopharyngiomas.
AB  - During the years 1988-1992, 50 patients with large cystic craniopharyngioma were
      treated with stereotactic injection of radionuclide. The patients aged from 3 to
      69 (average 21) years. Of these patients, 36 were primary cases and 14 were
      recurrences after previous major surgery. The cyst volume of craniopharyngiomas
      was 28-126 cm(3) (average 38 cm(3)). The Leksell stereotactic system was used for
      injection of radionuclides Au-198, P-32 and Y90. Eighty-four injections were
      performed in 50 patients; additional injections took place at intervals of 1-6
      months. There were no operative deaths and no serious complications. The follow
      up period ranged from 1 to 5 years (average 2.6 years). Eighty-six percent of
      patients improved clinically and computed tomography re-examination confirmed
      shrinkage of the cysts.

PMID- 18638949
TI  - Are mitochondrial DNA deletions causative in chronic progressive external
      ophthalmoplegia patients?
AB  - Twenty-one patients with long standing unexplained ptosis (3), chronic
      progressive external ophthalmoplegia (CPEO, 16) or Kearns-Sayre syndrome (KSS, 2)
      were studied for the presence of mitochondrial DNA (mtDNA) deletions and the
      major disease-associated mtDNA point mutations with the aim of correlating
      mitochondrial genetic abnormalities with pathogenesis in these patients. Only 52%
      were found to have a deletion; of these, 82% harboured the 'common deletion'. Two
      of 2 KSS patients and 9 of 16 CPEO patients were deletion positive. None of the 3
      patients with bilateral ptosis only had a deletion. Of those patients with ragged
      red fibres (RRF) on histology, 69% had a deletion. No disease associated mtDNA
      point mutation was observed with the exception of the nucleotide (nt) 11084 A-G
      mutation associated with mitochondrial encephalopathy, lactic acidosis and stroke
      like episodes (MELAS) in a patient also harbouring the common deletion. The role
      of deletions in CPEO patients is discussed.

PMID- 18638950
TI  - Intracranial rebleeding in moyamoya disease.
AB  - Cerebral ischaemia and intracranial haemorrhage are the major catastrophic events
      in the natural course of moyamoya disease. To prevent cerebral ischaemia
      extracranial/intracranial (EC/IC) bypass surgery has been done and the results of
      the surgery have been well documented. However, the mechanism(s) underlying
      intracranial bleeding and the therapeutic modalities used to prevent bleeding
      have not been well elucidated. We have retrospectively analysed 45 cases with
      intracranial haemorrhage among 192 patients with moyamoya disease treated and
      followed at our institute. Analysis of the initial patients with haemorrhage did
      not provide any new information other than the already reported theories about
      the origin and mechanism of bleeding. Analysis of 15 patients in whom haemorrhage
      occurred at least twice suggested that there were two different mechanisms of
      rebleeding. One group consisted of 7 cases, where haemorrhages were confined to
      the original bleeding site. In 3 of these 7 cases a small aneurysm was identified
      at the periphery of a moyamoya vessel. In 1 case a ruptured aneurysm was found on
      a major vessel. In 3 other cases no source of bleeding was identified. In all but
      1 of these cases rebleeding occurred within 2 months after the initial ictus. The
      second group consisted of 8 cases where haemorrhage occurred repeatedly but at
      variable sites. In none of these cases were aneurysms or other vascular
      abnormalities identified to suggest the source of bleeding and in all of these
      cases rebleeding occurred more than 2 months after the initial ictus. In moyamoya
      disease intracranial bleeding may occur as a result of rupture of a tiny aneurysm
      situated at the periphery of the moyamoya vessels and which may have been
      destroyed after the initial bleeding. If the aneurysms persist after rupture they
      may re-rupture after a fairly short interval. In other cases bleeding occurs at
      different sites from the initial haemorrhage; these are considered to be a result
      of rupture of weak moyamoya vessels which are forced to act as collateral
      pathways and are under unusually increased haemodynamic stress. EC/IC bypass
      surgery is considered to be effective for the prevention of rebleeding in both
      groups of patients but in selected cases. Direct surgery is recommended when a
      peripheral aneurysm is found on a moyamoya vessel which has bled once.

PMID- 18638951
TI  - The effects of morphine and midazolam on EEGs in neonates.
AB  - We investigated the effect of morphine, midazolam and their active metabolites on
      background electroencephalogram (EEG) in 6 neonates undergoing extracorporeal
      membrane oxygenation (ECMO) by conducting simultaneous EEGs and serum drug
      levels. Despite serum levels that were sufficient to produce adequate sedation,
      no patients had burstsuppressed or flat EEG backgrounds. We did, however, note
      that scalp oedema caused by prolonged immobility led to artefactual attenuation
      of EEG background. We conclude that an EEG prior to sedation will provide
      important baseline information that allows subsequent comparison and an awareness
      that scalp oedema after prolonged sedation and immobility will reduce
      misinterpretation of artefactual EEG attenuation.

PMID- 18638952
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is a recently described genetic disease
      characterized by recurrent subcortical infarcts and dementia. Based on linkage
      analysis its gene has been assigned to chromosome 19p13. We report an Australian
      kindred with typical clinical features of CADASIL, the diagnosis being supported
      by linkage analysis. No expansion was detected on repeat expansion detection
      (RED) testing.

PMID- 18638953
TI  - Brain tumours in infancy: a clinicopathological study.
AB  - To investigate the clinicopathological features of brain tumours occurring in the
      first year of life, the records of the Department of Histopathology at the
      Adelaide Children's Hospital were examined for cases where the initial diagnosis
      of intracranial neoplasm had been made in infancy. Surgical material was
      available for review from 1972 to 1993 and autopsy cases were reviewed for an
      additional 12 years from 1962 to 1993. Twenty-four infants with intracranial
      neoplasms were diagnosed ranging in age from 5 days to 1 year (average = 7
      months). There were 23 surgical cases and 1 autopsy case. The male to female
      ratio was 17:7. Fifty-eight percent of the tumours were located in the
      supratentorial region. Although the incidence is relatively low, this study
      demonstrates that a wide range of brain tumours, which differ significantly in
      both clinical presentation and location from those found in the older child, do
      occur during the first year of life. The location of the primary tumour may be
      affected by associated congenital malformations, and metastatic malignancy,
      although rare, may occur. Antenatal ultrasound examination may be useful in
      identifying congenital intracranial tumours.

PMID- 18638954
TI  - Cerebral control of saccades and neuropsychological test results after head
      injury.
AB  - Abnormalities in the control of saccades have been described in patients with
      cerebral pathology.(1, 2) We assessed control of visually guided, reflexive and
      volitional saccades in 16 patients suffering severe traumatic brain injury and 12
      controls and related the results to deficits on neuropsychological tests of speed
      of information processing and goal directed behaviour. All saccadic latencies
      were prolonged. Suppression of inappropriate saccades was impaired on volitional
      saccade tests which proved to be more sensitive in identifying impairment of goal
      directed behaviour than the neuropsychological test results. Patients' self-paced
      saccade rate was lower than controls' and correlated with performance on several
      visually mediated neuropsychological test results. Patients' visually guided,
      reflexive saccades were hypometric; this hypometria correlated with both visual
      and non-visual neuropsychological test results and with post-traumatic amnesia
      duration. Hypometria in reflexive saccades may reflect diffuse brain injury. Re
      examination after 12 months revealed that the control of volitional saccades
      improved but there was no improvement in the visually guided reflexive saccade
      measures. The volitional saccade tests may be useful in documenting both
      impairment and subsequent recovery.

PMID- 18638955
TI  - Diagnosis of unruptured asymptomatic cerebral aneurysms by magnetic resonance
      angiography.
AB  - The purpose of this study was to assess the incidence of unruptured asymptomatic
      cerebral aneurysms detected by magnetic resonance angiography (MRA). Three
      thousand patients without major neurological deficit had undergone MRA. MRA was
      obtained using three-dimensional time-of-flight method. Among the 3000 patients
      examined, 80 unruptured asymptomatic aneurysms were discovered in 68 patients
      (2.3%). Twenty-six were located on the internal carotid artery, 28 on the middle
      cerebral artery, 17 on the anterior communicating artery, 1 on the posterior
      cerebral artery and 8 on the vertebro-basilar artery. Thirty-seven patients
      underwent surgery. Mortality was zero and morbidity was 5%. Three patients who
      declined surgery died of subarachnoid haemorrhage in the ensuing 2.5 years.

PMID- 18638956
TI  - Relationships within the idiopathic generalized epilepsies.
AB  - The relationships between the various epileptic syndromes, which comprise the
      idiopathic generalized epilepsies that commence after infancy, were explored in
      451 patients by comparing the incidences of various clinical and
      electroencephalographic features in subsets of the patients, determined primarily
      by their clinical patterns of seizure phenomena (absences, myoclonic and
      generalized tonic-clonic seizures), and secondarily by their ages at the onset of
      their seizures. The approach showed a bimodal distribution of ages of onset in
      the absence epilepsy group only. More subjects whose absences had begun under 10
      years of age experienced very frequent episodes (52.0% vs 26.9%) and fewer
      experienced generalized tonic-clonic seizures (44.0% vs 71.2%). These differences
      were consistent with the distinction made in the International League Against
      Epilepsy's Classification between childhood and adolescent onset absence
      epilepsy. There were no unambiguous age of onset related differences in the
      incidences of the features studied within each of the myoclonic seizure and the
      generalized tonic-clonic seizure only groups, although there were differences in
      the incidences of the features between the two groups. Thus the idiopathic
      generalized epilepsies studied appeared to comprise a number of discrete entities
      rather than a smooth continuum of age of onset related epileptic phenomena.

PMID- 18638957
TI  - Ossification of the posterior longitudinal ligament of the cervical spine.
AB  - Although ossification of the posterior longitudinal ligament (OPLL) of the
      cervical spine is an uncommon condition, its strong prevalence among the Japanese
      and non-Japanese Asians is well known. Genetic predisposition coupled with ageing
      and an imbalance in bone-seeking hormones are some actiological factors
      postulated in recent years. Imaging is directed at showing the calcified mass,
      cord compression and any attendant damage, as the latter are important prognostic
      factors. We describe 6 cases of OPLL of the cervical spine seen at Westmead
      Hospital between 1979 and 1994. Of the 4 patients presenting with disabling
      compressive myelopathy, 3 made significant recovery following surgical
      decompression. Characteristic plain film features manifesting as a dense
      calcified linear structure along the course of the posterior longitudinal
      ligament (PLL) were present in 5 patients, including 1 who was asymptomatic.
      Computed tomography (CT) was invaluable in demonstrating the full extent of the
      disease in all 5 symptomatic patients. Magnetic resonance imaging (MRI) was
      helpful in excluding myelomalacia in 2 patients prior to successful surgery. The
      myelopathy caused by cervical OPLL remains rare, affecting mainly middle aged
      males of Asiatic and European extraction.

PMID- 18638958
TI  - The effects of reversible inactivation of the subthalamo-pallidal pathway on the
      behaviour of naive and hemiparkinsonian monkeys.
AB  - This study was designed to further investigate the role of the subthalamic
      nucleus (STN) and globus pallidus internus (GPi) in the pathophysiology of
      Parkinson's disease. The prevailing theory about the pathophysiology of
      Parkinson's disease (PD) predicts that there is overactivity of the subthalamo
      pallidal pathway. In order to inactivate that pathway, naive and hemiparkinsonian
      monkeys were locally administered either muscimol (to reversibly inactivate the
      contralateral STN) or kynurenic acid (to reduce glutamatergic activity in the
      contralateral GPi). Three naive and 2 hemiparkinsonian monkeys were studied.
      Intra-carotid MPTP was administered to produce 2 hemiparkinsonian monkeys.
      Injection sites of muscimol and kynurenic acid in the brain were confirmed
      electrophysiologically and histologically. Injections of muscimol into the STN in
      naive and hemiparkinsonian monkeys caused reversible contralateral dystonia, but
      did not alleviate Parkinsonism. Only one kynurenic acid injection into GPi
      partially alleviated Parkinsonism. On the basis of the results in this study,
      aspects of the currently accepted hypothesis of the pathophysiology of PD cannot
      be confirmed. However, this study reports that the STN has an important role in
      the production of dystonia. This experimental model of dystonia will prove
      suitable for further study of both the mechanisms causing dystonia as well as for
      possible therapeutic approaches to its treatment.

PMID- 18638959
TI  - No evidence of existence of functional 5-HT(1) receptors in isolated and perfused
      canine basilar arteries.
AB  - The vascular responses to intraluminally administered 5-hydroxytryptamine (5-HT),
      5-carboxamidotryptamine (5-CT, a 5-HT(1)-like receptor agonist), alpha-methyl-5
      hydroxytryptamine (alpha-M-5-HT, a 5-HT(2) receptor agonist) were examined,
      compared with those to noradrenaline (NA) and potassium chloride (KCl), in
      isolated and perfused canine basilar arteries using the steel cannula insertion
      method. These agonists usually elicited only a vasoconstriction in a dose related
      manner. Even in preconstricted preparations by 30 and 60 mM K(+) in modified
      Krebs solution, the injection of either 5-HT or 5-CT induced only monophasic
      constrictor responses without any dilation. The rank order of vasoconstrictive
      potency was 5-HT > alpha-M-5-HT >/= CT NA KCl. The constrictions to 5-HT, 5-CT
      and alpha-M-5-HT were significantly inhibited by ketanserin (a 5-HT(2) receptor
      antagonist), but not significantly blocked by methiothepin (a 5-HT(1) receptor
      antagonist). From these results, we concluded that 1) 5-HT induces a prominent
      vasoconstriction mainly due to an activation of 5-HT(2) receptors, 2) 5-CT
      induced constriction may be mostly mediated by 5-HT(2) but not 5-HT(1) receptors,
      and 3) there are no functional vasodilator 5-HT receptors in the canine basilar
      artery.

PMID- 18638960
TI  - Haemangioma calcificans presenting as intracranial haemorrhages during pregnancy.
AB  - A 33-year-old female with intracerebral haemorrhage during pregnancy, associated
      with subarachnoid and intraventricular haemorrhages, is presented. Intracranial
      haemorrhages during pregnancy are known to frequently result from cerebral
      aneurysms or arteriovenous malformations. We believe that this is caused by
      haemangioma calcificans and is noteworthy in considering the indications for
      surgical treatment for intracranial calcified lesions suggestive of cavernous
      haemangioma.

PMID- 18638961
TI  - Usefulness of spinal drainage for post-traumatic external hydrocephalus: report
      of two cases.
AB  - An 8-year-old girl presented with symptoms of increased intracranial pressure on
      the 18th day after removal of an occipital epidural haematoma. A 69-year-old
      woman exhibited the same symptoms on the 6th day after the removal of a left
      frontal subdural haematoma. Computed tomography (CT) revealed that both patients
      were suffering from external hydrocephalus. Spinal drainage, maintained for 18
      days in the former case and for 7 days in the latter, not only relieved those
      symptoms but also cured the external hydrocephalus. Recurrence of external
      hydrocephalus has not been observed in either case for several years since
      discontinuation of spinal drainage. Usefulness of spinal drainage for post
      traumatic external hydrocephalus is discussed.

PMID- 18638962
TI  - Paradoxical clinicoradiologic features of a cavernous dural arteriovenous
      malformation.
AB  - A case of bilateral Barrow type D dural arteriovenous malformations (DAVMs) of
      the cavernous sinuses is described in a 66-year-old woman who, despite having
      moderate symptoms with partial resolution and benign findings on non-invasive
      imaging, was ultimately found to have associated leptomeningeal venous drainage
      on conventional angiography. This case illustrates the problem of discordance
      between clinical symptoms, non-invasive imaging and actual radiologic features
      predisposing to aggressive clinical behaviour in DAVMs detected by conventional
      angiography.

PMID- 18638963
TI  - Intracranial chondroid chordoma.
AB  - Chordomas are rare tumours that arise from remnants of the primitive notochord.
      Chondroid chordoma is believed to be a variant of chordoma. We present a patient
      with a chondroid chordoma presenting with an oculomotor nerve palsy. Computed
      tomography (CT) demonstrated a mildly enhancing mass in the parasellar region and
      a markedly enhanced mass in the prepontine cistern. Magnetic resonance imaging
      also demonstrated a moderately enhanced, dumb-bell shaped mass. The parasellar
      mass was removed and the oculomotor nerve palsy disappeared three months after
      operation. Histology of the resected specimen revealed chondroid chordoma. One
      year after surgery she developed a left hemiparesis. CT demonstrated haemorrhage
      in the prepontine tumour. The encapsulated tumour with haematoma was removed and
      histology revealed that the tumour was composed of only chordoma tissue without
      cartilaginous tissue. The tumours located in the parasellar region and prepontine
      cistern enhanced differently on CT.

PMID- 18638964
TI  - Sinus pericranii: a clinical and radiological review of an unusual condition.
AB  - Sinus pericranii is an unusual and rare condition characterized by an abnormal
      communication between an intracranial venous sinus and the extracranial venous
      circulation. Patients are usually children and often asymptomatic, presenting
      only when cosmetic concerns are raised by the parents or the presence of a scalp
      lump is noted. The diagnosis is made on clinical grounds with supportive evidence
      from radiological investigations such as plain skull X-rays, CT scans, MR scans
      and cerebral angiography. The treatment may be conservative but surgical excision
      is usually required, whether for cosmetic integrity or for fear of direct trauma
      with life threatening haemorrhage. The aetiology and pathophysiology of this
      condition remains poorly understood. We present a case of a 6-year-old boy with
      sinus pericranii that was treated with surgical excision and repair. The
      radiological investigations employed to confirm the diagnosis are presented,
      including a Doppler ultrasound of the lesion. We also present a review of the
      literature on this condition.

PMID- 18638965
TI  - Hunter syndrome complicated by hydrocephalus and an endogenous anticoagulant.
AB  - This case illustrates the features of Hunter syndrome (mucopolysaccharidosis type
      2) complicated by hydrocephalus and a prolonged activated partial thromboplastin
      time (APTT). Ventriculo-peritoneal shunt insertion was performed but was
      complicated by an extradural haematoma which was successfully drained. Other
      neurological complications of Hunter syndrome include compressive cervical
      myelopathy, diffuse cerebral white matter changes and punctate lesions in the
      basal ganglia. This case is the first report of a coagulation defect in a patient
      with Hunter syndrome.

PMID- 18638966
TI  - 'Splinter in the mind': a case of penetrating periorbital injury.
AB  - A case of penetrating orbitocranial injury in a 12-year-old boy is described. The
      orbital injuries are usually obvious on presentation and receive prompt attention
      but a high index of suspicion is needed together with specialized imaging to
      diagnose the frequently coexistent intracranial penetration. Intracranial
      suppuration is the major complication with combined mortality from all
      complications reported to be as high as 25%. The value of aggressive antibiotic
      therapy and formal exploration is emphasized and the importance of wood as a
      particularly hazardous foreign body is stressed.

PMID- 18638967
TI  - Fixed dilated pupils in association with a thiopentone infusion in severe head
      injury.
AB  - We report a case of thiopentone induced mydriasis in a 17-year-old, head injured
      patient. Two initial 50 mg intravenous boluses and 12 h of a 125 mg/h infusion
      (total of 1500 mg) of thiopentone were used to reduce intracranial pressure in
      this patient. The patient developed fixed dilated pupils (> 8 mm) and hypothermia
      (27 degrees C). Thiopentone plasma concentrations were performed giving a level
      of 309 mumol/1; withdrawing the thiopentone infusion resulted in the pupil
      diameter returning to 5 mm within 24 h. A new drug plasma concentration was
      performed revealing a level of 198 mumol/1. We discuss the clinical implications
      of such a drug response and review the relevant literature.

PMID- 18638968
TI  - De novo development of intracranial cavernous angioma.
AB  - We report on the de novo development of intracranial cavernous angiomas. The
      patient is a 16-year-old boy with multiple cavernous angiomas who has experienced
      four episodes of intracerebral haemorrhage. Our investigations suggest that
      repeat magnetic resonance imaging (MRI) is recommended for routine follow-up
      monitoring.

PMID- 18638969
TI  - Haemangiopericytoma presenting as recurrent intracranial haemorrhage.
AB  - A 17-year-old girl presented with intracranial haemorrhage from a malignant
      haemangiopericytoma. During the course of treatment with surgery, radiotherapy
      and chemotherapy there were three further episodes of intracranial haemorrhage
      over a 9-month period, culminating in death from the effects of raised
      intracranial pressure. The pathology of haemangiopericytoma is reviewed with
      particular reference to factors predisposing to haemorrhage.

PMID- 18638970
TI  - Acute presentation of meningioma due to haemorrhage following a motor vehicle
      accident.
AB  - Only three previous cases have been reported in which trauma has precipitated
      haemorrhage from a meningioma. This case is unique due to its occurrence after a
      minor motor vehicle accident. Our patient presented with transient weakness and
      sensory loss of the right lower leg following a motor vehicle accident and the
      subsequent occurrence of focal seizures prompted a computed tomography scan of
      the head which revealed a large parasagittal meningioma with intratumoural
      haemorrhage. The tumour was successfully removed with complete recovery. The
      literature related to haemorrhage from meningiomas following trauma is reviewed.

PMID- 18638971
TI  - Chloroma of the cranium with dural involvement.
AB  - An unusual case of chloroma (granulocytic sarcoma) of the cranium with
      involvement of underlying dura and presenting as an intracranial space occupying
      lesion, with no systemic evidence of myeloid leukaemia, is reported. Operative
      removal was followed by local radiation. The patient is well and no systemic
      evidence of leukaemia has been manifested nearly 4 years after operation. The
      literature is reviewed.

PMID- 18638972
TI  - The neurosurgery workforce in Australia and New Zealand: a report.

PMID- 18638974
TI  - Challenges of head injury management for the third millenium.

PMID- 18638973
TI  - Detection, isolation, and characterization of high molecular weight double
      stranded RNAs in plants infected with velvet tobacco mottle virus.
AB  - Two species of double-stranded (ds) RNA were detected in Nicotiana clevelandii
      infected with velvet tobacco mottle virus (VTMoV) which were not present in
      healthy plants. The ds-RNAs were first detected by polyacrylamide gel
      electrophoresis 2 to 4 and about 8 days after inoculation in the inoculated and
      systemically infected leaves respectively. Thereafter the concentrations of ds
      RNA increased significantly. The VTMoV-specific ds-RNA was purified from plants
      10 to 14 days after inoculation. The ds-RNA was electrophoresed on agarose gels,
      transferred to nitrocellulose paper and blot hybridized with 32P-labelled probes
      specific to nucleotide sequences of either the positive or negative sense strands
      of the various VTMoV RNA components: the linear single-stranded (ss) RNA 1 of Mr
      about 1.5 x 10(6) or RNAs 2 and 3, the circular and linear forms respectively, of
      viroid-like ss-RNA with Mr of about 1.2 x 10(5). One of the ds-RNA species, with
      Mr of about 2.8 x 10(6), was shown to contain base sequences specific to RNA 1
      and the other, with Mr of about 3.6 x 10(6), specific to RNAs 2 and 3. The
      possible significance of the VTMoV-specific ds-RNAs to replication of the virus
      is discussed.

PMID- 18638975
TI  - Experimental neuronal protection in cerebral ischaemia Part II: Potential
      neuroprotective drugs.
AB  - The search for agents that could protect neurons from ischaemia-induced death has
      largely been based upon knowledge of the pathophysiological events that cause
      neuronal damage. Thus, the main classes of drugs that have been tested in animal
      experiments include ion channel blockers, those targeting neurotransmitter
      receptors, calpain inhibitors, inhibitors of enzymes in the arachidonic acid
      cascade, antagonists of platelet-activating factor, antioxidants and antagonists
      of inflammatory cytokines. The therapeutic potential of neurotrophins, growth
      factors and gangliosides has also been explored. As this review indicates, nearly
      all of these drugs have demonstrable neuroprotective capabilities. Broad spectrum
      neuroprotective drugs appear to have more potential than specifically targeted
      drugs, a finding which is in keeping with the multifactorial nature of ischaemia
      induced neuronal death.

PMID- 18638976
TI  - Effects of left temporal lobectomy and amygdalohippocampectomy on memory.
AB  - This study examined the effects of left (dominant) temporal lobe surgery on
      verbal and visual memory in 38 patients with temporal lobe epilepsy. Twenty-five
      patients had anterior temporal lobectomy (ATL) and 13 had selective
      amygdalohippocampectomy (AH). All were administered the Rey Auditory Verbal
      Learning Test and a Complex Figure Test preoperatively and 1 year after surgery.
      ATL resulted in better seizure control overall. The ATL group as a whole showed a
      greater postoperative decline of their verbal memory than the AH group. A closer
      examination of the ATL patients showed there was a subgroup (n = 11) with better
      preoperative memory functioning that had the most significant decline. In
      contrast, only three patients in the AH group had better preoperative memory, and
      the majority (n = 10) matched the 'memory impaired' ATL patients. The changes in
      memory performance of the 'memory impaired' ATL and AH patients did not reach
      statistical significance. Postoperatively all patient groups improved in their
      verbal fluency.

PMID- 18638977
TI  - Stroke prevention in patients with non-valvular atrial fibrillation: a current
      community perspective.
AB  - Non-valvular atrial fibrillation (NVAF) is responsible for up to 10% of all
      ischaemic strokes. The risk of stroke in these patients is substantial,
      particularly when associated with past cerebral ischaemia, hypertension, diabetes
      and age over 65. Warfarin has recently been shown to reduce this risk by two
      thirds with relative safety. The files of 103 patients with chronic NVAF on
      recent presentation to hospital were studied to see if they had been given
      warfarin beforehand. Two-thirds would have been ideal candidates, having at least
      one added risk factor for stroke, and no contraindication for the use of
      warfarin. Yet fewer than 10% were taking it. Sixteen of these 103 patients had an
      ischaemic event at presentation, mostly stroke. Twelve were ideal candidates for
      warfarin prophylaxis, but none had received it for this purpose. Much more must
      be done to prevent stroke in these patients.

PMID- 18638978
TI  - Management of moderate and severe head injury in neurosurgical units in
      Australasia.
AB  - A survey of the 31 neurosurgical units in Australia and New Zealand was
      undertaken by the Trauma Committee of the Neurosurgical Society of Australasia to
      determine areas of common practice and areas of divergence in management
      protocols in the treatment of moderate and severe head injury. Intracranial
      pressure (ICP) measurement was a fundamental component of care in the majority of
      units with rises in ICP being treated by sedation, mild hyperventilation
      (p(a)CO(2) of 30-35 mm Hg) and osmotherapy or cerebrospinal fluid drainage as
      first choices. Where the ICP was measured selectively following a severe head
      injury, the computed tomography appearance was used as the criterion for
      initiation of measurement. All units used at least an arterial line, a central
      venous pressure monitor and end-tidal CO(2) measurement routinely to monitor
      progress. Attention to the cerebral perfusion pressure with volume support and
      pressors, together with less intense hyperventilation, were the most common
      alterations to management protocols made over the preceding 2 years.

PMID- 18638979
TI  - Anterior cervical discectomy without fusion: a comparison with Cloward's
      procedure.
AB  - The antero-medial microsurgical disc or osteophyte removal without formal
      interbody fusion is a surgical alternative in the treatment of cervical discs
      causing radicular compression or cervical myelopathy. In the past 20 years 379
      patients underwent anterior surgery, including 240 microdiscectomies without
      graft and 139 Cloward's dowel procedures. The long-term results of both
      procedures are compared in patients suffering from radicular compression,
      dominant myelopathy and radiculo-myelopathy. We found no statistically
      significant differences between the two methods treating three different
      conditions. The improvement rate in patients with soft and sequestrated discs is
      generally better compared to those with hard discs and spondylotic changes.
      Functional stability of the cervical spine is present in 92% of cases treated
      without interbody fusion immediately after surgery. A complete osseous fusion
      after a period of 6-12 months was found in 90% of Cloward procedures and in 81%
      of discectomy without graft. No definite correlation was found between the
      clinical improvement and the radiological results. According to our experience
      the Cloward's fusion procedure has no long-term advantages over discectomy
      without graft except in cases of severe myelopathy caused by multilevel ventral
      compression due to osteophytes. No permanent postoperative complication was
      encountered. Most of the treated patients returned to their previous activities.

PMID- 18638981
TI  - Cranioplasty and the syndrome of the trephined.
AB  - Cranioplasty has been practised since prehistoric times. Some of the indications
      for cranioplasty remain controversial as does the existence of the 'syndrome of
      the trephined'. This report describes a patient in whom neurological improvement
      occurred repetitively following cranioplasty and in whom deterioration recurred
      following removal of the cranioplasty plate.

PMID- 18638980
TI  - Magnetic resonance angiography of experimental cerebral vasospasm.
AB  - The purpose of this study was to observe spastic cerebral arteries by magnetic
      resonance angiography (MRA) and to establish acetazolamide reactivity of these
      vessels. After control studies using MRA and conventional angiography,
      subarachnoid haemorrhage (SAH) was induced on day 0 in 7 Japanese monkeys. MRA
      and conventional angiography were then repeated on day 7 to observe the
      development of cerebral vasospasm. Reactivity of cerebral vessels to
      acetazolamide was also studied in both control animals (angiography before SAH)
      and on day 7 after SAH. Cerebral vasospasm was detected by both conventional
      angiography and MRA on day 7. The arteries on the side of the clot were more
      spastic than those on the control side. MRA was superior to conventional
      angiography in demonstrating dilatation of both control arteries (before SAH
      induction) and vasospastic arteries (on day 7 after SAH) after administration of
      acetazolamide.

PMID- 18638982
TI  - Subarachnoid hemorrhage and vasospasm following removal of craniopharyngioma.
AB  - A patient who had transcranial removal of a craniopharyngioma developed a large,
      postoperative subarachnoid hematoma in the basal cisterns. The patient developed
      cerebral vasospasm with infarction. A review of the literature found 20 cases of
      vasospasm associated with surgical removal of intracranial tumors. These cases
      were reviewed to determine the role of subarachnoid blood in the causation of
      vasospasm. In most cases, vasospasm is caused by subarachnoid blood. Multiple
      causes for arterial narrowing may be present, such as radiation vasculopathy,
      iatrogenic arterial injury and infection, and may be impossible to exclude as
      factors contributing to arterial narrowing.

PMID- 18638983
TI  - Demonstration of membranous aqueduct occlusion by fast multiphase magnetic
      resonance imaging.
AB  - Membranous aqueduct occlusion is one of the few causes of obstructive
      hydrocephalus that is amenable to direct surgical treatment. Conventional
      diagnostic methods may not delineate this entity. The advent of dynamic fast
      multiphase magnetic resonance imaging has improved the definition of the
      aqueductal membrane by enabling visualization of the obstructed cerebrospinal
      fluid flow within the ventricular system. We report a case of a 10-year-old boy
      in whom the diagnosis of membranous aqueduct occlusion was only achieved
      utilizing this new technique.

PMID- 18638984
TI  - Cancer associated retinopathy and non-small cell lung cancer.
AB  - The syndrome of cancer associated retinopathy is a relatively recently described
      entity that has characteristic clinical and electrophysiological features. It is
      most closely associated with small cell carcinoma and a specific antibody against
      a retinal protein. We present a patient with cancer associated retinopathy and a
      non-small cell lung cancer. The diagnosis of the clinical syndrome led to the
      discovery of the tumour. The antibody was not present. Therapy with chemotherapy,
      corticosteroids and plasma exhange did not improve the retinopathy. Earlier
      recognition of the syndrome may be important in detecting malignancy and
      attempting treatment of the retinopathy before irreversible damage is done.

PMID- 18638985
TI  - Cerebral cortical venous reconstruction using saphenous vein graft.
AB  - Cortical venous reconstruction using saphenous vein graft was performed in a
      patient during a procedure for meningioma removal. A cortical vein passing by the
      tumour was accidentally sacrificed during the dural opening. Before tumour
      removal the cortical vein was reconstructed with a 2-cm length of saphenous vein
      graft. Intraoperative venous blood flow control was done by microvascular Doppler
      sonography, obtaining a venous blood flow velocity at 3 cm/s. Postoperative
      course of the patient was uneventful. Angiographic control at one year after
      operation revealed good venous graft patency. Saphenous vein graft may be an
      option for reconstruction of cerebral cortical veins.

PMID- 18638986
TI  - Ectopic pituitary fossa thyroid tissue.
AB  - Developmental anomalies of the thyroid gland may result in ectopic glandular
      tissue. We report a unique case of ectopic thyroid tissue within the pituitary
      fossa and sphenoid sinus, associated with a lingual thyroid gland. The aetiology
      of this ectopic tissue is postulated to be ascent of primitive thyroid endoderm
      at the time of formation of Rathke's pouch.

PMID- 18638987
TI  - Computed tomography and magnetic resonance imaging of the brain in hypoglycaemic
      encephalopathy.
AB  - A diabetic man suffering from a hypoglycaemic attack presented to our hospital.
      Magnetic resonance imaging (MRI) findings were grossly abnormal and difficult to
      interpret. The computed tomographic appearance simulated multiple infarctions.
      The MRI appearance simulated a space occupying lesion. Literature review of the
      radiology and the pathophysiology of hypoglycaemic brain damage is provided.
      Comparison between our findings and previous reports is also given.

PMID- 18638988
TI  - Suspected MPTP-induced parkinsonism.
AB  - The case of an intravenous heroin user who developed parkinsonian symptoms from
      the age of 28 years is presented. Neuropathologic examination revealed a marked
      loss of neurons and gliosis with the presence of Lewy bodies in the substantia
      nigra and locus ceruleus; they stained variably with antibody to ubiquitin and
      negatively with antibodies to tau and neurofibrillary tangles. Pseudo-Lewy bodies
      were also seen. Electron microscopy showed features in keeping with other
      electron microscopic studies of Lewy bodies in idiopathic Parkinson's disease and
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced inclusion bodies in
      monkeys. Given that the deceased was a known heroin user, the rarity of the early
      age of onset, that MPTP is a recognized cause of parkinsonism in the drug abusing
      population, the absence of history of exposure to neuroleptics and the
      neuropathologic features, the parkinsonism was considered to be due to MPTP
      contamination of heroin. However, given the onset of parkinsonism 11 years prior
      to death it was not possible to obtain samples of the heroin injected to test for
      the presence of MPTP. Therefore it could not be absolutely excluded that this was
      a case of idiopathic Parkinson's disease occurring at a very young age in a
      heroin abuser. The immunohistochemical and electron microscopic features of Lewy
      bodies in such a case have not been previously described. The similarity of the
      neuropathological features to those of idiopathic Parkinson's disease and MPTP
      induced parkinsonism further strengthens the hypothesis of MPTP or an MPTP-like
      agent being a cause of idiopathic Parkinson's disease.

PMID- 18638989
TI  - Spinal cysticercosis.

PMID- 18638990
TI  - Surgical treatment of transitional internal carotid aneurysms.
AB  - Ten transitional internal carotid aneurysms are presented. Necks and domes of
      these aneurysms were located in both the intradural subarachnoid and extradural
      intracavernous spaces across the carotid dural ring. Seven aneurysms were small,
      2 were large, and 1 was giant. Two patients had subarachnoid haemorrhage (SAH), 2
      compressive symptoms, 5 SAH from rupture of associated lesions (aneurysms or AVM)
      and 1 case was an incidental finding. Direct clipping was performed successfully
      in all patients. The overall surgical outcome was excellent in all patients, with
      transient complications in 4 cases. It is suggested these aneurysms should be
      treated with direct clipping whether ruptured or not because of the risk of SAH.
      A classification of paraclinoidal region aneurysms including cavernous sinus
      aneurysms extending into the intradural subarachnoid space is proposed.

PMID- 18638991
TI  - Australian association of neurologists annual scientific meeting, 1997.

PMID- 18638992
TI  - Stroke society of australasia annual scientific meeting, 1996.

PMID- 18638993
TI  - A comparative study on the in vitro translation products of individual RNAs from
      two-, three-, and four-component strains of barley stripe mosaic virus.
AB  - Passaging through plants of the three-component barley stripe mosaic virus (BSMV)
      strain Norwich (Norwich III) yielded a two-component isolate (Norwich II). A
      study was made of the sets of polypeptides translated in a rabbit reticulocyte
      and wheat embryo cell-free systems from individual RNAs of (1) the natural three
      component strain Norwich III, (2) a two-component isolate derived from the former
      (Norwich II), and (3) an isolate intermediate between the three- and two
      component ones, Norwich;. Translation of RNA 1 from all three variants of the
      Norwich strain in vitro yields a single major product with a molecular weight
      (Mr) of 120,000 (p120). RNA 2 from Norwich III in vitro produces two
      polypeptides: the viral coat protein (p23) and, in certain ionic conditions, a
      polypeptide of 25,000 M(r) (p25). RNA 3 from Norwich III is translated into a
      protein with Mr of 75,000 (p75). Conversion of Norwich III into Norwich II is
      accompanied by the changes in the coding specificity of RNA 2; beside the coat
      protein and p25, a protein of 85,000 M(r) (p85) is formed upon its translation-a
      feature characteristic of RNA 2 of the naturally occurring bipartite BSMV strains
      (Russian, type). With the Norwich(i) variety, which is marked by a significantly
      reduced portion of RNA 3 in the total virion RNA preparation, RNA 2 in addition
      to the coat protein, p25, and p85 directs the synthesis of another product with
      M(r) of about 78,000. Thus, in conversion of the three-component BSMV into a two
      component one, the loss of RNA 3 is concomitant with the actuation in RNA 2 of a
      sequence coding for p85. RNAs 1-3 of the quadripartite Argentina Mild (AM) BSMV
      strain code in vitro for the same polypeptides as RNAs 1-3 of Norwich III. AM RNA
      4 is translated as a monocistronic template into a polypeptide with Mr of 55,000
      (p55). Amino acid sequences of p85, p75, and p55 are shown to overlap among these
      polypeptides but not to appreciably overlap with p120 sequences. Data presented
      here allowed a tentative structure to be proposed for genome of two-, three-, and
      four-component BSMV strains.

PMID- 18638994
TI  - Genomic divergence among single-nucleocapsid nuclear polyhedrosis viruses of
      plusiine hosts.
AB  - The DNAs of five single-nucleocapsid baculoviruses (S-NPVs) from plusiine hosts
      were compared. Restriction endonuclease fragments of three geographical isolates
      of Trichoplusia ni S-NPVs and isolates of Pseudoplusia incluens and Syngrapha
      selects viruses were compared using a battery of enzymes which included EcoRI,
      BamHI, SalI, SmaI, and HindIII. The results show that T. ni and P. includens S
      NPVs are distinct, but related, viruses and that the S. selecta virus is a strain
      of T. ni S-NPV. Minor differences in geographical isolates of T. ni S-NPVs were
      detected. The data are generally consistent with the host-range properties of
      these viruses, suggesting that the combination of DNA restriction profiles and
      host-range matrices may provide a valuable tool for the identification and
      cataloging of the plusiine S-NPVs.

PMID- 18638995
TI  - Sequence relations and coding properties of a subgenomic RNA isolated from barley
      stripe mosaic virus.
AB  - A subgenomic (SG) RNA ( approximately 800 nucleotides) is a minor component of
      barley stripe mosaic virus RNAs. The SG-RNAs isolated from the Type and North
      Dakota 18 (ND18) strains of BSMV have sequence homology with RNA 2 of the
      ("pseudo-two component") Type strain, which has two electrophoretic components,
      but only limited homology is evident with RNA 2 of the ND18 and Norwich strains,
      which have three electrophoretic components ("three component" strain). Instead,
      eDNAs from SG-RNA hybridize most efficiently with RNA 3 of the ND18 and Norwich
      strains. In wheat germ extracts the SG-RNAs direct the synthesis of two
      polypeptides with apparent molecular weights of 20 to 21 x 10(3). However, these
      two polypeptides were difficult to detect by polyacrylamide gel electrophoresis
      of extracts from Type- or ND18-infected barley and so appear not to accumulate
      during infection.

PMID- 18638996
TI  - Nucleotide sequence of the coat protein cistron and the 3' noncoding region of
      cucumber green mottle mosaic virus (watermelon strain) RNA.
AB  - Double-stranded cDNA copies of cucumber green mottle mosaic virus (watermelon
      strain, CGMMV-W) RNA polyadenylated in vitro were cloned into the pBR322 at the
      PstI site. The sequence of 1071 nucleotides from the Tend of the genomic RNA was
      determined using two recombinant plasmids and the genomic RNA. The coat protein
      cistron was located in residues 176-661 from the 3' end. The coat protein was
      composed of 160 amino acid residues with the molecular weight of 17,261. The 3'
      noncoding region of the CGMMVW genome was 175 nucleotides long and highly
      homologous to that of the common strain of TMV. The assembly origin of
      reconstitution is positioned within the coat protein cistron as predicted
      previously. In the 5' flanking region of the coat protein cistron a long open
      frame, probably of 30K protein, was found. The predicted 30K and the coat protein
      cistron would overlap each other as is the case of the cowpea strain of TMV.

PMID- 18638997
TI  - The spherically averaged structures of cowpea mosaic virus components by X-ray
      solution scattering.
AB  - The X-ray diffraction patterns of the four components of cowpea mosaic virus
      isolated from a cesium chloride gradient were measured, using film methods, to 30
      A resolution. Diffraction patterns were analyzed by fitting computed two-shell
      spherical models to the observed data. The fitting procedure was applied to data
      to 80 A resolution to avoid the nonspherical contribution to the pattern observed
      at higher resolution. At pH 7.0 all four components displayed the same external
      spherically averaged radius of 140 +/-2 A. The lowest density component (top),
      which contains no RNA, was best modeled by an empty shell with an outer radius of
      140 A and an inner radius of 101 +/- 3 A. The middle component, containing 27%
      RNA by weight, was modeled with a uniform electron density sphere. The bottom
      upper and bottom lower components, which are biologically identical but display
      different buoyant densities in cesium chloride solutions, were analyzed
      independently. The bottom upper component was best modeled with a 101 A inner
      (RNA containing) sphere of mean electron density 0.453e-/A(3) and a 101 to 140 A
      outer (protein containing) shell of electron density 0.410e-/A(3). The bottom
      lower component was fit with the same model except that the RNA containing region
      displayed a mean electron density of 0.459e-/A(3). The implications of the
      spherically averaged component structures for the protein structure, RNA and
      protein hydration, and cesium binding to RNA are discussed.

PMID- 18638998
TI  - Properties of the tobacco mosaic virus intermediate length RNA-2 and its
      translation.
AB  - The existence of subgenomic RNAs is well established in the case of plant viruses
      such as tobacco mosaic virus (TMV). However, except for the subgenomic coat
      protein mRNA, it is not known whether the other subgenomic RNAs have a function
      in the life cycle of the virus. In search of more information about one of the
      major subgenomic RNAs-intermediate length RNA-2 or I2 RNA-of TMV, in vitro and in
      vivo translational studies were performed. The I2 RNA, which codes in vitro for
      the synthesis of a 30K (K = kilodalton) protein, appears to be uncapped as judged
      by the need of different in vitro translation conditions for the synthesis of
      this protein, compared to the conditions required for the synthesis of the 126K
      and 183K proteins coded by the capped genomic RNA. In vivo a protein migrating in
      the same position as the 30K protein synthesized in vitro can be detected in
      infected tobacco leaves. Since this protein occurs transiently early upon
      infection, whether it is virus-coded or virus-induced, it could have an early
      function during infection.

PMID- 18639000
TI  - Changing concepts of diffuse axonal injury.

PMID- 18638999
TI  - Cucumber mosaic virus-associated RNA 5: X. The complete nucleotide sequence of a
      CARNA 5 incapable of inducing tomato necrosis.
AB  - The complete nucleotide sequence of a cucumber mosaic virus-associated RNA 5
      (CARNA 5) that does not induce the tomato necrosis disease (J. M. Kaper, M. E.
      Tousignant, and S. M. Thompson, Virology 114, 526-533, 1981) has been determined
      and compared with the known sequence of a necrosis-inducing CARNA 5 (K. E.
      Richards, G. Jonard, M. Jacquemond, and H. Lot, Virology 89, 395-408, 1978). The
      nonnecrotic satellite RNA, (1)CARNA 5, is one nucleotide smaller yet 93%
      homologous with (n)CARNA 5, the necrosis-inducing satellite RNA. (1)CARNA 5
      differs from (n)CARNA 5 by 21 substitutions, 3 deletions, and 2 insertions, with
      more changes in the 3' half than in the 5' half of the molecule. (1)CARNA 5, like
      (n)CARNA 5, is capped at its 5' terminus; the nucleotide sequences predict that
      putative translational products of the two RNAs could be significantly different.

PMID- 18639001
TI  - Apoptotic neuronal death following cerebral ischaemia.
AB  - Transient cerebral ischaemia accompanies a number of disease processes, including
      stroke, subarachnoid haemorrhage and head injury, that have a profound social and
      economic impact on our community. The development of neuroprotective agents that
      reduce the morbidity associated with these diverse conditions requires an
      understanding of the mechanisms of neuronal death following cerebral ischaemia.
      There is increasing evidence that a significant proportion of neurons die
      following ischaemia by a process called apoptosis. Apoptosis involves the
      activation of a highly regulated series of intracellular events in which the
      neuron actively participates in its own death. Genes such as bcl-2 and
      proteolytic enzymes such as the caspases, which have been shown to play an
      important role in apoptotic cell death in other cell types, are now being
      investigated for their role in apoptotic neuronal death. This review will focus
      on current knowledge of the intracellular pathways of apoptosis, with particular
      reference to their role in ischaemic neuronal death.

PMID- 18639002
TI  - A review of cerebral vasospasm. Part IV. Post-traumatic vasospasm.
AB  - Cerebral vasospasm is increasingly recognized as contributing to ischaemia after
      head injury. The reported incidence of post-traumatic vasospasm (PTV) varies
      between 10% and 90%, probably largely because of differences in patient
      selection, in definitions of vasospasm and in methods of detecting spasm. In
      severe head injury, based on studies with similar criteria, the incidence is
      approximately 40%. PTV is often associated with traumatic subarachnoid
      haemorrhage (tSAH), but has been reported without tSAH. These two factors are
      independently associated with poor outcome, but the direct links between tSAH,
      vasospasm and outcome are uncertain. There is evidence that calcium antagonists
      improve outcome in patients with head injury and tSAH; aminosteroids may also be
      effective here. Other strategies such as maintaining normocapnia and control of
      blood volume and pressure may also be useful. Further investigation of large
      cohorts is required to clarify fully the significance of PTV, its relationship
      with tSAH and outcome and possible treatment modalities.

PMID- 18639003
TI  - Endovascular treatment of intracranial aneurysms.

PMID- 18639004
TI  - Dreamy mental states in late 20th century neurology.
AB  - In 1895 Sir James Crichton-Browne lectured on the dreamy mental states that had
      largely gone unnoticed until his old friend John Hughlings Jackson had first
      recognized them nearly 20 years earlier as a component of some epileptic
      seizures. In 1897 Jackson described the association between such dreamy states
      and pathology in the uncinate gyrus of the brain, thus delineating the phenomenon
      of uncinate (temporal lobe) epilepsy. Crichton-Browne's account of dreamy states
      is easier to follow than Jackson's various writings on the subject, and makes it
      clear that such states are not always epileptic in nature. Jackson believed that
      epileptic dreamy states were not due to the brain areas responsible being
      involved by the epileptic discharge itself, but were release phenomena resulting
      from the discharge inactivating higher levels of brain function. In the century
      since Jackson, there has been little advance in understanding of the detailed
      mechanisms of production of the various abnormal psychic experiences which occur
      in these dreamy states which, following Kinnier Wilson's analysis 1928, are now
      more usually considered in terms of their individual components.

PMID- 18639005
TI  - Management of giant intracranial aneurysms of the posterior circulation.
AB  - Between 1980 and 1995, 14 patients underwent treatment at Royal Prince Alfred
      Hospital for giant posterior circulation aneurysms. Two (14%) patients presented
      with subarachnoid haemorrhage (SAH). Eight (57%) of the 14 giant aneurysms were
      located at the basilar caput. A total of 7 (50%) contained significant
      intraluminal thrombus. Surgery was undertaken in 10 (72%) patients and
      endovascular embolization in the remaining 4 (28%). Of the patients treated
      surgically, 3 underwent clipping and a further 4 underwent Hunterian ligation. Of
      the 4 patients in whom embolization was carried out, 2 were coil treated and 2
      balloon treated. Six (60%) patients undergoing surgery experienced significant
      complications, but in only 4 (40%) surgically treated patients was the
      complication directly attributable to the surgical procedure. All 4 (100%)
      patients treated interventionally suffered major complications, and in 3 (75%) of
      these the complication was directly attributable to the endovascular procedure.
      The clinical outcome at a median of 12 months follow-up was favourable in 8 (62%)
      of the 13 patients for whom follow-up information was available. We conclude that
      radiological techniques are not satisfactory for direct treatment of giant
      posterior circulation aneurysms and surgical exploration is advisable. In
      addition, timely referral to, and well planned management at, an experienced
      centre will undoubtedly contribute significantly towards securing a more
      favourable overall outcome.

PMID- 18639006
TI  - Association of acute inflammatory demyelinating polyneuropathy with acute
      lymphoblastic leukaemia and HLA-A11.
AB  - Acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome)
      developed in three patients receiving chemotherapy for acute lymphoblastic
      leukaemia or the closely related entity lymphoblastic lymphoma, a relationship
      that has not been previously described. The HLA-A11 antigen was expressed by all
      patients, two of whom were Chinese, raising the possibility of a genetically
      based immunological predisposition to GBS in this patient group.

PMID- 18639007
TI  - Anterior cervical graftless fusion for soft disc protrusion. A review of 509 disc
      excisions in 476 patients.
AB  - A series of 509 disc excisions in 476 consecutive patients is reported. All
      excisions were for radiologically confirmed disc protrusion. Ninety-one per cent
      fusion occurred at the discectomy levels. Good symptomatic improvement of
      brachialgia (89%) was achieved with 73% improvement of neck pain but only 53%
      improvement of headache. Equivalent results to anterior interbody fusion with
      fewer complications indicate that anterior cervical discectomy should be
      considered for the management of cervical disc protrusion.

PMID- 18639008
TI  - Pharmacokinetic and clinical evaluation of liquid L-dopa/carbidopa in Parkinson's
      disease.
AB  - The aim of the study was to assess the pharmacokinetic properties and clinical
      effectiveness of L-dopa/carbidopa solution treatment in patients with
      parkinsonian motor fluctuations. No significant difference in maximal L-dopa
      concentration, time to peak L-dopa concentration and area under curve was found
      in single dose studies which compared equivalent tablet and solution L
      dopa/carbidopa doses in 9 patients. Seven out of 10 patients treated with hourly
      doses of liquid L-dopa/carbidopa were improved after switching from conventional
      tablet medication. Less 'off' time per day and less 'off' phase disability were
      the usual benefits. Six of these patients maintained this improvement and
      continued on long-term liquid medication. The benefits of this treatment do not
      relate to improved L-dopa delivery to the bloodstream. The ability of patients to
      fractionate the treatment into small, frequent doses which can be used more
      flexibly than tablets appears to confer the main advantages of liquid L
      dopa/carbidopa in the management of parkinsonian motor fluctuations.

PMID- 18639009
TI  - A study of classification of spontaneous intraventricular haemorrhage: a report
      of 324 cases.
AB  - In order to develop a practical classification of spontaneous intraventricular
      haemorrhage (IVH), a correlation was made between clinical and computed
      tomographic (CT) factors in 324 patients with IVH between September 1988 and
      December 1996. Spontaneous IVH was graded according to age, blood pressure,
      clinical conditions, conscious state on admission, primary site of bleeding,
      volume of intraparenchymal haematoma, degree of midline shift, degree of
      hydrocephalus and location of IVH, producing a score up to 20. A score of 0-5 was
      Grade I, 6-10 Grade II, 11-15 Grade III, 16-20 Grade IV. The mortality of each
      Grade, respectively, was 1.6%, 22.5%, 76% and 100%. The authors propose that this
      grading system may be a practical schema in the evaluation of the prognosis for
      IVH.

PMID- 18639010
TI  - Extracranial orbital decompression for optic neuropathy in Graves' eye disease.
AB  - Optic neuropathy affects a small proportion of patients with Graves' eye disease.
      It is due to optic nerve compression by enlarged extraocular muscles and can be
      treated by corticosteroids, irradiation or surgical orbital decompression. The
      current report evaluates the effectiveness of extracranial orbital decompression
      performed by one surgeon for optic neuropathy in Graves' eye disease. The records
      of 21 patients (33 orbits) undergoing extracranial orbital decompression for
      Graves' optic neuropathy were analysed for changes in visual acuity and colour
      vision and reduction in proptosis. Visual acuity and colour vision improved in
      all 33 eyes in the short-term postoperatively (4 weeks), but later deteriorated
      in 5 eyes (6.6%) of 4 patients (19%). The remainder maintained improved vision
      for the duration of the follow-up period (mean 22, range 3-54 months). Proptosis
      decreased by a mean 5.0 mm (range 1-8). Extraocular muscle imbalance and diplopia
      worsened in 9 21 patients (43%) and improved in 2 21 (9.5%). The patients having
      medial wall and floor decompressed all had worse diplopia (5 5 ), those with
      medial and lateral wall worsened in 4 10 cases and improved in 1 10 , and those
      having all three walls decompressed had no cases of worsening diplopia and 1 6
      improved. All patients with symptomatic diplopia achieved binocular single vision
      in a useful range after one and sometimes two squint procedures. No patient lost
      vision as a result of the extracranial orbital decompression, but one lost vision
      in one eye after transfrontal decompression following failed extracranial
      decompression. Extracranial orbital decompression is effective in improving
      vision and reducing proptosis in most patients with optic neuropathy in Graves'
      eye disease, but induces or worsens diplopia in a high proportion of patients.
      The diplopia is readily correctable, and the change to decompressions that
      include the lateral wall may reduce the risk of postoperative diplopia.

PMID- 18639011
TI  - Reproducible peracute glutamate-induced focal lesions of the normal rat brain
      using microdialysis.
AB  - The neurotoxic effect of the excitatory amino acid neurotransmitter glutamate was
      first demonstrated 20 years ago, but the recent development of potent glutamate
      antagonist drugs with effects against ischaemic damage in vivo and their
      introduction in clinical studies has made 'excitotoxicity' a major focus of
      current interest. Despite this, the factors influencing glutamate neurotoxicity
      in vivo are poorly understood, and the role of glutamate as a neurotoxin in vivo
      is contested. By using a microdialysis probe to deliver glutamate to the normal
      rat cortex, we have devised a reproducible model of peracute 'excitotoxic'
      damage. We have demonstrated that concentrations of over 20 mM glutamate in the
      perfusate kill neurons in the intact brain in less than 90 min -20 to 200 times
      more than that required for toxicity in mixed cell culture. The histological and
      ultrastructural features of the glutamate lesion are very similar to those of
      acute ischaemia, although their development is much more rapid after glutamate.
      True extracellular glutamate concentrations estimated from microdialysis studies
      (about 4 mM) are not far from our results. The reproducible quantifiable nature
      of the glutamate lesions in this model make it well suited to study the factors
      affecting the excitotoxic process in vivo.

PMID- 18639012
TI  - Neurocysticercosis.
AB  - Neurocysticercosis is an infection of the central nervous system by the larvae of
      the pork tapeworm Taenia sodium. Worldwide it represents the commonest parasitic
      infection of the central nervous system. However, in Australia, only a small
      number of cases have been previously recognized. Three cases of
      neurocysticercosis are reported which illustrate a variety of presentations and
      diagnostic problems encountered. With the introduction of effective
      chemotherapeutic agents, current medical and surgical management is reviewed.

PMID- 18639013
TI  - Colloid cyst of the third ventricle in opposite sex, non-twin siblings.
AB  - This report describes a colloid cyst of the third ventricle presenting in a 23
      year-old woman. Subsequently, her brother presented with a similar colloid cyst
      also at 23 years of age. In both patients the cysts were successfully surgically
      removed. The cysts were examined by light microscopy utilizing
      immunohistochemical staining. The epithelial lining was essentially identical in
      both cases. Both cysts stained positively for cytokeratin and epithelial membrane
      antigen and negatively for S100, vimentin, carcinoembryonic antigen and glial
      fibrillary acidic protein. A genetic predisposition to this congenital condition
      may be present in some relatives of patients in whom colloid cysts have been
      detected.

PMID- 18639014
TI  - McArdle's disease resembling an inflammatory myopathy.
AB  - Previous reports have shown that McArdle's disease may occasionally present in
      older patients (i.e. greater than 40 years of age) as a progressive myopathy that
      is clinically and sometimes electrophysiologically indistinguishable from
      idiopathic polymyositis. We report two such patients who in addition had muscle
      biopsies showing inflammatory infiltrates compatible with polymyositis. However,
      subsequent enzyme histochemistry demonstrated complete myophosphorylase
      deficiency and, in the absence of an alternative explanation, may be the reason
      for the inflammatory changes seen. These cases highlight the importance of a
      thorough evaluation of patients with an 'inflammatory myopathy' and the
      occasional diagnostic confusion that may arise in differentiating metabolic
      myopathies from idiopathic polymyositis. Diagnostic clarification is important to
      avoid the use of incorrect and potentially toxic treatment.

PMID- 18639015
TI  - Tuberculous spinal cord compression in pregnancy.
AB  - A case of tuberculous spinal cord compression causing acute paraparesis in a
      pregnant woman of 33 weeks gestation is described. Immediate Caesarean section
      followed by aggressive surgical decompression of the spine via an anterior
      approach with reconstruction achieved a good outcome for mother and fetus. The
      management of tuberculous spinal cord compression in pregnancy is discussed, with
      particular reference to the timing of delivery. We recommend early decompression
      of the spine if there is progressive neurological compromise. The fetal
      management is secondary.

PMID- 18639016
TI  - Growth of multiple hydatid cysts evaluated by computed tomography.
AB  - A case of multiple hydatid cysts, of embolic origin from a cyst of the left
      atrium, is discussed. The patient was first admitted to hospital with an
      intracerebral haemorrhage and was treated conservatively. There was not any
      cystic or mass lesion other than intracerebral haemorrhage on his computed
      tomography (CT) scans. In the follow-up period, the CT scans after 14 months
      showed multiple hydatid cysts, with the largest about 6 cm in diameter, which
      suggested a growth rate of 5 cm per year.

PMID- 18639017
TI  - Proximal myotonic myopathy: a report of a kindred.
AB  - We describe a family with an autosomal dominant myotonic myopathy with absence of
      the abnormal CTG expansion characteristic of myotonic dystrophy. We believe that
      the findings in this family concur with those of recent case reports which have
      postulated the existence of a new adult onset myotonic disorder, distinct from
      myotonic dystrophy: 'proximal myotonic myopathy'.

PMID- 18639018
TI  - Restenosis after transluminal angioplasty for atherosclerotic vertebral and
      subclavian artery stenosis.
AB  - A total of 34 stenotic lesions of the vertebral or subclavian artery were treated
      in 29 patients using percutaneous transluminal angioplasty (PTA). Seventeen
      patients were followed angiographically for up to 2 years after PTA. Of 17
      patients, five (29.4%) had restenosis which developed between 3 and 6 months
      after the procedure. Of these patients, two were treated by repeat angioplasty
      uneventfully, two were treated by surgical reconstruction, and the fifth is being
      observed without treatment while the patient remains asymptomatic. Neointimal
      fibromuscular hyperplasia as seen in the surgically resected specimens was
      thought to be the major cause of restenosis after PTA. Indications of PTA for
      vertebrobasilar and subclavian artery restenosis are discussed.

PMID- 18639019
TI  - A case of pneumocephalus secondary to VP shunt in a patient with acoustic
      neuroma.
AB  - Pneumocephalus is an uncommon complication of ventriculo-peritoneal (VP) shunts.
      We present a case of pneumocephalus secondary to a VP shunt in a patient with an
      acoustic neuroma. The site of the cerebrospinal fluid fistula was found to be
      into an extensive petrous apex air cell system due to tumour erosion of the
      internal auditory canal.

PMID- 18639020
TI  - Granulomatous angiitis following primary varicella zoster infection.
AB  - Granulomatous angiitis is an uncommon but well recognized complication of
      varicella zoster infection. The classic presentation is of a delayed hemiparesis
      in an often immunocompromised patient following zoster ophthalmicus. This report
      outlines the case of a young woman who developed a large left middle cerebral
      artery territory infarct secondary to granulomatous angiitis during primary
      varicella zoster infection.

PMID- 18639021
TI  - Diffuse leptomeningeal spread of pleomorphic xanthoastrocytoma.
AB  - Diffuse meningeal spread and dural infiltration by pleomorphic xanthoastrocytoma
      occurring after initial diagnosis of a left frontotemporal lesion is reported.
      The unusual pattern of spread and aggressive course for a pleomorphic
      xanthoastrocytoma are discussed.

PMID- 18639022
TI  - Infected subdural hematoma.
AB  - A case is presented in which Escherichia coli seeded a pre-existing chronic
      subdural hematoma. A 77-year-old woman was admitted to our hospital because of
      lethargy, left hemiparesis and fever. Drainage through a burr hole was performed
      with the diagnosis of bilateral chronic subdural hematoma. Operative findings
      revealed the infected subdural hematoma on the right side and non-infected
      subdural hematoma on the left side. Cultures of the subdural hematoma grew
      Escherichia coli. In view of the pyuria, the etiology of the infected subdural
      hematoma was postulated to be a urinary tract infection. In the majority of 14
      reported cases, the causative organisms were Escherichia coli, Salmonella, and
      the systemic sources of infection included the urinary tract, gastrointestinal
      disease, or were unknown. The possibility of infected subdural hematoma should be
      considered when computed tomography findings suggestive of chronic subdural
      hematoma exist in a patient with signs of infection.

PMID- 18639023
TI  - Distal aneurysm of the rostral duplicate anterior inferior cerebellar artery
      feeding an associated dural arteriovenous malformation: case report and review of
      the literature.
AB  - A rare case of a distal aneurysm of a rostral, duplicate anterior inferior
      cerebellar artery feeding an associated dural arteriovenous malformation is
      reported. The patient presented with severe nuchal rigidity after sexual
      intercourse; no neurological deficit was seen. The aneurysm causing the
      subarachnoid hemorrhage was wrapped but the arteriovenous malformation was
      inoperable. An analysis of the literature showed 51 cases of coexisting aneurysms
      and arteriovenous malformations in the posterior fossa; only three of them had a
      dural arteriovenous malformation. A 7:3 male predominance was recognized. The
      mean age at diagnosis was 48.5 years. Ninety-four per cent presented with
      hemorrhage and 6% with cranial nerve deficit only. The bleeding originated from
      the aneurysm in 73% and from the arteriovenous malformation in 15%; in 12% the
      origin of bleeding was not mentioned or could not be identified. Outcome was
      satisfactory in 76%, poor in 7% and 17% died. Treatment of both lesions should be
      performed in a one-stage operation if technically feasible. Additionally,
      radiosurgery to surgically unresectable arteriovenous malformations should be
      considered in cases where aneurysms are clipped or coiled.

PMID- 18639024
TI  - Transient visual obscurations and headache in aqueduct stenosis exacerbated by
      menstruation.
AB  - The influence of female sex hormones is implicated in the pathogenesis of benign
      intracranial hypertension, but their effect on intracranial pressure (ICP) in
      other settings is not known. We report a 23-year-old white female with catamenial
      exacerbations of transient visual obscurations and headache suggestive of raised
      ICP. The patient had obstructive hydrocephalus secondary to stenosis of the
      aqueduct of Sylvius associated with a Chiari type I malformation. Exacerbation of
      raised ICP during the menstrual period was the most likely cause of her symptoms.
      Female sex hormones may influence the secretion or absorption of cerebrospinal
      fluid in conditions other than BIH.

PMID- 18639025
TI  - Modification of the fatty acid composition of phospholipids during the
      hypersensitive reaction in tobacco.
AB  - When Nicotiana tabacum cv. Xanthi nc. plants were inoculated with tobacco mosaic
      virus (TMV), grown at 33 degrees for 6 days, then transferred to 25 degrees C to
      induce necrotic reaction, a rapid saturation of microsomal phospholipid-bound
      fatty acids was observed. Lipoxygenase activity increased to four times that of
      the control activity prior to the observed changes in both the fatty acid
      saturation and the increase in permeability.

PMID- 18639026
TI  - Lucerne transient streak virus RNA and its translation in rabbit reticulocyte
      lysate and wheat germ extract.
AB  - Two abundant, encapsidated RNAs of lucerne transient streak virus (LTSV) are the
      1.5 x 10(6) molecular weight (Mr) linear RNA-1 and both circular (RNA-2) and
      linear (RNA-3) forms of a 0.15 x 10(6) Mr viroid-like RNA. Two additional
      discrete minor RNAs, Mr 0.35 x 10(6) and 0.07 x 10(6), and a heterogeneous
      mixture of RNAs in the Mr range 0.05 to 1.0 x 10(6) are reported. Principal
      polypeptides translated from unfractionated LTSV RNA in rabbit reticulocyte
      lysate were of Mr 105,000 (p105), 78,000 (p78), and 33,000 (p33), the last not
      easily detected after translation in wheat germ extracts. All apparently are
      encoded in RNA-1. However, p33, which was precipitated by antibody of LTSV
      particles and presumably is the major capsid protein, was more readily translated
      from a smaller, most likely the Mr 0.35 x 10(6), RNA. Partial proteolysis and
      other tests indicate that p105 has a carboxyl terminal extension of p78 amino
      acid sequences and that neither shares sequences with p33. No translation
      products were attributed to RNA-2, RNA-3 or the Mr 0.07 x 10(6) RNA.

PMID- 18639027
TI  - Molecular cloning of DNA complementary to tobacco vein mottling virus RNA.
AB  - RNA isolated from tobacco vein mottling virus (TVMV) was used as a template for
      avian myeloblastosis virus RNA-dependent DNA polymerase, primed with oligo(dT).
      The largest single-stranded cDNA synthesized was 10 kb, the same as the viral
      RNA. This material was converted to double-stranded cDNA with Escherichia coli
      DNA polymerase I and digested with restriction endonuclease HindIII. The cDNA
      fragments were ligated to HindIII-digested plasmid pBR322 and the product used to
      transform E. coli strain DG-75. Clones containing recombinant plasmids were
      selected by ampicillin resistance, and those containing TVMV RNA sequences were
      selected by colony hybridization with a single-stranded cDNA probe. Four
      different sizes of recombinant plasmid were reproducibly observed. The inserted
      DNA portion could be excised in each case with HindIII. The lengths of inserted
      DNA were 3.0, 1.85, 1.1, and 0.72 kb. A similar procedure was used with PstI
      digested cDNA and pBR322. A single type of recombinant plasmid, containing a DNA
      insertion of 1.85 kb, was reproducibly observed. Hybridization with TVMV RNA
      confirmed that the five inserted DNA segments were derived from the viral RNA.
      Hybridization of each recombinant plasmid with the others established that each
      of the cloned HindIII fragments was unique and that one of them overlapped the
      cloned PstI fragment. The cloned cDNA fragments were ordered by establishing a
      restriction map of the cDNA. Together the cloned cDNA fragments account for over
      80% of the viral genome.

PMID- 18639029
TI  - Spina bifida: An unfinished story.

PMID- 18639028
TI  - Human leukocyte interferon and the antiviral factor (AVF) from virus-infected
      plants stimulate plant tissues to produce nucleotides with antiviral activity.
AB  - Leaves of Nicotiana glutinosa and tobacco, as well as tobacco callus cultures,
      were treated with the plant antiviral factor AVF or with a purified subspecies of
      human leukocyte interferon. After incubation, a fraction containing short
      oligonucleotides was extracted directly from the plant tissue. In addition, a
      synthetase preparation was fractionated from treated tissues, which polymerized
      ATP in the presence of polyinosinic, polycytidylic acid (poly(I:C)). The various
      plant nucleotides were applied to tobacco mosaic virus (TMV)-infected leaf disks,
      the TMV content of which were determined by an enzyme-linked immunosorbent assay.
      The nucleotide fraction extracted directly from TMV-infected leaves exhibited a
      considerable antiviral activity, whereas similar fractions from AVF- or
      interferon-treated leaves did not, even though an antiviral state was induced in
      the tissue by these agents. However, when the synthetase fraction from TMV
      infected, AVF-treated, or interferon-treated tissues was incubated with ATP and
      poly(I:C), the resultant, heat-stable, acid-soluble, polymerized ATP markedly
      inhibited TMV multiplication. It is concluded that the presence of double
      stranded RNA is obligatory for the formation of the antiviral nucleotides. The
      analogy to interferon-induced resistance in animal tissues is discussed.

PMID- 18639030
TI  - Dominantly inherited ataxias. Part I.

PMID- 18639031
TI  - Medulloblastoma in the first year of life: A report of five cases.
AB  - Five infants with cerebellar medulloblastoma, who all presented within the first
      year of life, are presented. The initial characteristic presenting symptoms
      included vomiting and macrocrania, frequently followed by a delay in normal
      development. No patients showed any signs or symptoms of cerebellar dysfunction.
      One infant, who was initially diagnosed as having a congenital hydrocephalus,
      died 4 months after undergoing a cerebrospinal fluid shunt operation, while the
      remaining four patients all underwent direct surgery for their tumors and three
      also received an additional course of postoperative radiation therapy. Of these
      four patients, three died within 4 years after diagnosis, with a mean survival
      period of 2.7 years, whereas one is still alive after a follow-up period of more
      than 20 years. However, the patient does suffer from both physical and
      intellectual handicaps. The clinical and histological features of infantile
      medulloblastomas are reviewed while the therapeutic problems associated with
      these tumors are also discussed.

PMID- 18639032
TI  - Assessment of cerebral blood flow by its frequency distribution in cerebral
      vascular diseases.
AB  - Cerebral blood flow (CBF) was measured by the stable xenon inhalation method, and
      the frequency distribution of flow levels analysed in patients with intracerebral
      haemorrhage, subarachnoid haemorrhage (SAH), vascular disease involving major
      arteries, lacunar infarction and normal subjects. The frequency distribution was
      skewed towards lower CBF values, and the mode, at which the frequency of values
      was highest, was lower than the mean CBF. Furthermore, the frequency at the mode
      was higher when mean CBF was low. Since many areas of the brain had lower flow
      than the mean CBF, it is suggested that attention must be paid to local flow
      levels as well as the overall mean value. A small decrease in mean CBF may mean
      the development of significant ischaemia in many regions.

PMID- 18639033
TI  - Subarachnoid haemorrhage of unknown cause: Clinical, neuroradiological and
      evolutive aspects.
AB  - The clinical and radiological data of 52 patients with subarachnoid haemorrhage
      (SAH) and a negative panangiography were analysed with an average follow-up
      period of 3.8 years. Of these 52 patients, only one (1.9%) was subsequently found
      to have an aneurysm. Second angiography proved to be inconclusive in all 24 cases
      where it was performed. Of the 51 'true' non-aneurysmal SAH, 80% were in a good
      clinical grade on admission and 12% developed cerebral ischaemia. The mortality
      rate following SAH was 4%. There was one rebleeding. At follow-up examination,
      87% of the patients had made a good recovery and 6% were left disabled due to
      SAH. Four patients with an aneurysmal pattern of SAH required a permanent shunt.
      All of the 22 patients with a perimesencephalic SAH were in a good neurological
      condition upon admission; one of them developed an angiography-induced transient
      cerebral ischaemia and another one suffered from a fatal rebleeding. None of the
      21 survivors was disabled at follow-up examination. The clinical course of
      patients with SAH of unknown cause, especially those with a perimesencephalic
      pattern of haemorrhage, is good. Repeated angiography in this latter group is not
      useful. In the aneurysmal pattern SAH group, repeat angiography is advised only
      if there is strong computed tomographic (CT) scan suspicion of an aneurysm.

PMID- 18639034
TI  - Transarterial platinum coil occlusion of ruptured intracranial aneurysms: results
      in 51 patients.
AB  - Fifty-one patients with subarachnoid haemorrhage (SAH) due to ruptured
      intracranial aneurysm have been treated by the Guglielmi detachable platinum coil
      (GDC) treatment method; 36 patients within 28 days of the ictus. There was total
      body occlusion in 64.8%, subtotal body occlusion in 24.1% and failed coil
      placement in 11.1%. Technical success rates were highest in aneurysms with neck
      sizes up to 4 mm (75% total occlusion) and aneurysms smaller than 10 mm largest
      diameter (72.5% total occlusion). At discharge from primary care, there were
      62.7% without deficit rising to 74.5% at follow-up assessment. Four patients are
      dead and one disabled (9.8%). Patient clinical outcomes relate most closely to
      Hunt and Hess grade at time of definitive treatment. Higher initial grades and
      poorer clinical outcomes are concentrated in patients treated in the first 14
      days. The incidence of procedure related thrombo-embolic events has fallen from
      20% in the first 30 patients to 4.8% in the next 21. Rebleeding during GDC
      procedures occurred in 20.6% of patients treated 1-14 days post SAH.

PMID- 18639035
TI  - Vagus nerve stimulation for seizure control: Local experience.
AB  - Vagus nerve stimulation (VNS) is a relatively new therapeutic approach for
      intractable epilepsy. Its safety and efficacy have already been documented by
      randomized clinical studies conducted in Europe and North America. To date, more
      than 800 vagus nerve stimulators have been implanted throughout the world. We
      report here our 6 cases of VNS in Chinese epileptic patients and present the
      results. The indications for this device, and also its associated problems, are
      also discussed.

PMID- 18639036
TI  - Intraoperative wound infiltration with bupivacaine in patients undergoing lumbar
      spine surgery.
AB  - We conducted a randomized double-blind trial to evaluate the effect of
      intraoperative wound infiltration with bupivacaine 0.25% (1 ml/kg) compared to
      placebo (NaCl 0.9% 1 ml/kg) in patients undergoing lumbar spine surgery. Fifty
      two patients were entered in the trial and 50 completed it. Two methods of wound
      infiltration were assessed: (a) infiltration after partial wound closure and (b)
      infiltration prior to wound closure. Postoperatively patients received morphine
      sulfate on demand. Visual analog pain scores were recorded every 2 h for 12 h
      after the operation. Analgesia requirements were recorded over the duration of
      the study for each patient. The patients who received bupivacaine infiltration
      prior to wound closure had significantly reduced pain scores in the recovery room
      and used significantly less morphine in the first 2 h following the procedure.
      They also had reduced pain scores and reduced morphine demand in the first 10 h
      but this did not reach statistical significance. No difference was noted between
      the placebo group and those receiving infiltration after partial wound closure.
      It is concluded that infiltration of bupivacaine is a simple and safe aid in
      obtaining analgesia in patients undergoing lumbar spine surgery provided that it
      is infiltrated prior to wound closure.

PMID- 18639037
TI  - Low-grade supratentorial astrocytomas in adults: Management, immunohistochemical
      analysis and long-term follow-up.
AB  - A retrospective review of supratentorial, low-grade astrocytomas in adults over a
      10-year period (1983-1993) was performed. All 62 patients had computed tomography
      and surgery with histological and immunohistochemical analysis of the tumour.
      Radiotherapy was administered to all patients, regardless of the extent of
      surgical resection. Multivariate analysis showed that age of the patient at the
      time of surgery (P=0.008) and female sex (P=0.031) were the most important
      indicators of improved survival. No significant survival advantage was found with
      any particular symptom or symptom duration. Neither presence of a tumour cyst nor
      site of the tumour affected survival. Histological grading (St Anne-Mayo system)
      found 61 grade II astrocytomas (98%) and one grade I tumour. Six tumours (10%)
      were protoplasmic astrocytomas and 56 cases (90%) were diffuse fibrillary
      astrocytomas. Proliferation index derived from Ki-67 antibody staining and the
      presence of p53 protein expression were not significantly correlated with
      survival. Most patients underwent biopsy (79%) with 8% undergoing subtotal and
      13% total resection. Increased extent of surgical removal showed a trend towards
      an improved survival (P=0.05). No survival advantage was found with increasing
      radiotherapy dose. Median survival in the study population was 5.1 years, with
      survival rates of 70% at 2 years and 53% at 5 years. The follow-up period ranged
      from 1 to 10.5 years. Younger age, female sex and the extent of surgical
      resection are important prognostic factors in the management of low-grade
      astrocytomas, whereas the efficacy of postoperative radiotherapy needs further
      evaluation. The prognostic significance of Ki-67 and p53 expression in low-grade
      astrocytomas remains to be determined.

PMID- 18639038
TI  - Petrous apex meningiomas: an alternative surgical approach.
AB  - The literature describes a variety of surgical approaches to deal with
      meningiomas that involve the apex of the petrous bone and lie predominantly in
      the posterior fossa, e.g. the transpetrosal (translabyrinthine and
      transcochlear), the combined supra- and infratentorial, the subtemporal with or
      without pyramid resection, the suboccipital and the orbitozygomatic approaches.
      This study presents an alternative surgical approach, namely a modification of
      the occipital craniotomy with or without tentorial division. This approach was
      used for the removal of three petrous bone apex meningiomas which were medium to
      large in size and located predominantly in the posterior fossa with extension
      into the middle fossa. Complete tumour excision was achieved with no morbidity
      and no mortality.

PMID- 18639039
TI  - Surgical management of dural arteriovenous malformations of the cranium.
AB  - Ten patients undergoing surgical treatment of dural arteriovenous malformations
      of the cranium between June 1992 and June 1995 are presented. Indications for
      surgery were prevention of intracranial haemorrhage in eight cases and palliation
      of neurological deficits in two cases. The aim of surgery was attempted complete
      cure when considered technically feasible. Six patients underwent aggressive
      surgical resection in an ablation attempt and four underwent leptomeningeal
      venous disconnection only. In those undergoing aggressive surgical resection, one
      patient died, one was rendered disabled and angiographic cure was achieved in
      four without mishap. In those undergoing leptomeningeal venous disconnection,
      there was no mortality or morbidity but angiographic cure was achieved in only
      one of four patients. As a result of our experience our policy has changed. When
      the indications for surgery are to palliate leptomeningeal venous hypertension or
      as prophylaxis against future haemorrhage, interruption of the involved
      leptomeningeal venous drainage in the subarachnoid space without attempted cure
      is now the sole aim of surgery. The surgical technique employed should be based
      on the pathophysiological disturbance requiring correction rather than the
      resectability of the lesion.

PMID- 18639040
TI  - Long-term potentiation saturation in chronic cerebral hypoperfusion.
AB  - Chronic reductions in cerebral blood flow (CBF) of between 25 and 50%, in the
      absence of cerebral infarction, lead to impairments in hippocampal in vitro long
      term potentiation (LTP). This study set out to explore some of the properties of
      this impairment of LTP. LTP is an electrophysiological property known to occur in
      the hippocampus, a region known to be exquisitely sensitive to hypoxic or
      ischemic insults. Thus, assessing LTP is a novel way of assessing the effects of
      subtle ischemic insults. Five male Sprague-Dawley rats had arteriovenous fistulae
      created surgically in the neck to induce a state of chronic cerebral
      hypoperfusion (CCH) with the features described above. Five rats were used as age
      matched controls. Twenty-six weeks after fistula formation, the animals were
      prepared for in vitro hippocampal recording in a submerged tissue bath.
      Extracellular field potentials were recorded at the Schaffer collateral-CA1
      region, with a stimulus intensity that achieved a population spike amplitude of 1
      mV. After tetanic stimulation, the frequency and magnitude of LTP was compared
      between control and fistula animals. All animals in both these groups
      demonstrated LTP in contradistinction to our previous work where LTP was impaired
      in fistula animals when a higher intensity of stimulation was used. This
      indicates that the structures that are associated with the initiation and
      maintenance of LTP (most probably the ischemia-sensitive CA1 pyramidal cells) are
      saturated as the stimulus intensity is increased. Thus, at this lower intensity
      of stimulation LTP is preserved in the fistula animals, but found to be impaired
      as the stimulus intensity is increased. Consequently, this study provides further
      information on this newly identified subtype of chronic cerebral ischemia which,
      in time, after further studies in humans, may help to redefine therapeutic
      indicators for the management of cerebral arteriovenous malformation and severe
      cerebrovascular disease.

PMID- 18639041
TI  - Thrombolytic therapy by pro-Urokinase combined with tissue plasminogen activator
      in an acute internal carotid occlusion.
AB  - Acute occlusion of the internal carotid artery by a cardiac embolus was quickly
      recanalized by the new thrombolytic agent, pro-Urokinase, combined with tissue
      plasminogen activator, without any side-effects. This is the first reported case
      of thrombolytic therapy of a cerebral artery using these agents in combination.

PMID- 18639042
TI  - Osteoplastic mastoidectomy followed by single-flap temporo-suboccipital
      craniotomy: combined supra- and infratentorial approach.
AB  - The combined supra- and infratentorial transpetrosal approach requires a
      subtemporal-suboccipital craniotomy and a mastoidectomy to unroof the dural
      sinuses. We describe a modified surgical technique that reduces the bone defect
      in the mastoid area and decreases the risk of violating the dural sinuses. Before
      the craniotomy, a surface mastoidotomy - the removal of the outer layer of the
      mastoid process - is carried out using a drill and a chisel for later
      reconstruction of the mastoid process. This is followed by a deep mastoidectomy
      in conjunction with petrosectomy to unroof the sigmoid sinus. Through a cavity
      made by the mastoidectomy, the lateral sinus is dissected from its bony groove. A
      single flap temporo-suboccipital craniotomy is performed necessitating few burr
      holes or none. Upon closure the temporo-occipital bone flap and mastoid flap are
      fixed together. The surface mastoidotomy followed by single-flap temporo
      occipital craniotomy minimizes the bone defect in the mastoid area. In addition,
      beginning such a procedure with a mastoidectomy facilitates safe dissection of
      the outer dura covering the sinuses and adherent to the bony groove.

PMID- 18639043
TI  - Subependymoma of the lateral ventricle presenting with sudden onset.
AB  - A 52-year-old man presented with sudden onset of severe headache, fever, mental
      confusion and mild signs of left hemisphere dysfunction. Computed tomographic and
      magnetic resonance imaging findings suggested a preoperative diagnosis of
      subependymoma of the left lateral ventricle, which was subsequently confirmed by
      surgery. The neoplasm could be totally removed and the postoperative clinical
      course was favourable. The reported case is unusual because symptomatic
      subependymomas of the lateral ventricle are definitely rare, and almost
      invariably present with a progressive clinical course over a period of weeks to
      years.

PMID- 18639044
TI  - Acute cervical cord injury complicating Klippel-Feil deformity and mimicking 'man
      in the barrel' syndrome.
AB  - This case illustrates the need to recognize a high cervical cord injury as a
      cause for bi-brachial weakness with intact bi-crural power, a pattern termed
      aptly by Sage as 'man in the barrel' syndrome. The patient who had an undiagnosed
      Klippel-Feil deformity had incurred his cervical injury after a collapse.

PMID- 18639045
TI  - Spinal dysraphism and the Currarino triad.
AB  - A female born with a lumbosacral lipomyelomeningocele, an associated foot-shaped
      appendage attached to her sacrum, sacral dysgenesis, anal atresia, a recto
      vaginal fistula and duplication of the right ureter is reported. We consider this
      case represents a pygomelus associated with a lipomyelomeningocele and an
      incomplete expression of Currarino's triad.

PMID- 18639046
TI  - Total removal of huge chondrosarcoma of the skull base with facial nerve
      resection and reconstruction.
AB  - Chondrosarcomas of the skull base are locally aggressive tumours, and radical
      surgical resection is often difficult because of involvement of important neural
      structures in the skull base. We report the successful total resection of a huge
      skull base chondrosarcoma extending both intra- and extracranially. The tumour
      involved the left mastoid process, entire petrous bone, jugular foramen,
      posterior fossa and the parapharyngeal space. Since the facial nerve in the
      fallopian canal was totally involved by the tumour, the nerve was sacrificed and
      reconstructed using a great auricular nerve graft. The removal of the tumour was
      radical and complete. The functional recovery of the reconstructed facial nerve
      was excellent. The patient has almost fully recovered from the other neurological
      symptoms and has been free of tumour recurrence for 4 years after surgery.

PMID- 18639047
TI  - Rendu-Osler-Weber syndrome: a current perspective on cerebral manifestations.
AB  - Rendu-Osler-Weber syndrome (hereditary haemorrhagic telangiectasia) is a vascular
      dysplasia characterized by recurrent epistaxis, mucocutaneous telangiectasia and
      a family history of the disorder. Although rare, it may cause significant
      morbidity to healthy and young individuals. We report three cases highlighting
      the cerebral manifestations of this disorder. These cases include cerebral
      abscess, cerebral haemorrhage and embolic stroke. These cerebral manifestations
      are due to complications associated with pulmonary arteriovenous fistulae or
      cerebral vascular malformations. The current management and screening for this
      disorder are reviewed.

PMID- 18639048
TI  - Hemiballismus due to contralateral sphenoid ridge meningioma.
AB  - Primary intracranial tumour is a very uncommon cause of hemiballismus. In our
      review of the literature only two verified cases were found: one meningioma and
      one meningoblastoma. We report a patient with right hemiballismus due to a
      contralateral meningioma of the sphenoid ridge. His symptoms disappeared
      completely after resection of the tumour. The patient had no signs of increased
      intracranial pressure. Possible pathogenic mechanisms are briefly discussed. A
      consequence of such an experience is that magnetic resonance imaging or computed
      tomography scans should be made of every patient with uncommon extrapyramidal
      disorders, particularly if they do not respond to drug therapy.

PMID- 18639049
TI  - Primary pineal and meningeal malignant melanomatosis.
AB  - Approximately 300 cases of primary meningeal melanoma have been reported in the
      literature;(1) eight of these cases had an associated pineal melanoma without
      additional parenchymal lesions.(2) We present another such case and demonstrate
      the advantage of magnetic resonance imaging over computed tomography in the early
      detection of meningeal involvement.

PMID- 18639050
TI  - Carotid-subclavian bypass for occlusion of the subclavian artery.
AB  - For surgical therapy of stenosis and occlusion of the subclavian artery, several
      types of extrathoracic vascular reconstructions have recently been performed,
      mainly in the supraclavicular fossa. Carotid-subclavian bypass is becoming a more
      acceptable surgical procedure than axilloaxillary bypass. We encountered three
      patients with these lesions who underwent common carotid-subclavian bypass with
      autogenous saphenous vein grafts. Their symptoms were completely relieved and
      pulsation of the radial artery recovered sufficiently. Restoration of inflow from
      the carotid artery was able to provide adequate reconstruction of the subclavian
      lesions. This bypass is less invasive and is efficient for such lesions in the
      supraclavicular position.

PMID- 18639051
TI  - Dissecting aneurysm of the middle cerebral artery associated with subarachnoid
      haemorrhage.
AB  - A 73-year-old male with known hypertension presented with subarachnoid
      haemorrhage due to a ruptured dissecting aneurysm of the middle cerebral artery.
      Angiography showed a dilatation with proximal and distal narrowing of the right
      middle cerebral artery. Conservative treatment resulted in almost complete
      resolution of the angiographic abnormalities 6 months later. Dissecting aneurysms
      of the middle cerebral artery with haemorrhagic manifestations are extremely rare
      and are not generally recognized as a cause of subarachnoid haemorrhage. If
      angiography fails to demonstrate a saccular aneurysm in a patient with
      subarachnoid haemorrhage, a ruptured dissecting aneurysm may be a possible cause.
      Repeat angiography should be performed for definitive diagnosis. More knowledge
      about the natural course is essential before determining whether surgical
      treatment is always necessary.

PMID- 18639052
TI  - Painful ophthalmoplegia caused by idiopathic hypertrophic cranial pachymeningitis
      in the cavernous sinus.
AB  - A 73-year-old man presenting with painful unilateral ophthalmoplegia is reported.
      Magnetic resonance imaging demonstrated a mass in the cavernous sinus extending
      to the floor of the middle cranial fossa. After resection of the lesion and anti
      tuberculous chemotherapy his symptoms improved. Pathological examination revealed
      extensive caseous necrosis.

PMID- 18639053
TI  - Inflammatory polyneuropathy in the setting of diabetes mellitus.
AB  - The authors report a patient with type II diabetes mellitus and an inflammatory
      polyneuropathy. The association is discussed and the importance of diagnosing
      treatable neuropathies in the diabetic patient is emphasized.

PMID- 18639054
TI  - Dominantly inherited ataxias. Part II.

PMID- 18639055
TI  - Innovative treatments: ethical requirements for evaluation.
AB  - An innovative surgical treatment may arise as a deliberate strategy to solve a
      clinical problem or as a serendipitous discovery in the course of clinical care.
      In either case there is a need to evaluate the procedure and there are ethical
      requirements on such evaluation concerning the reasons for its introduction,
      patient consent, patient safety and clinical efficacy. Some of these ethical
      considerations may tell against a randomized controlled trial but the need for
      monitoring and evaluation along with genuine informed consent remain as absolute
      requirements. Two cases are introduced and discussed, one of which concerns
      potentially dangerous surgery and the other a new technology. In each case the
      ethical requirements are examined and discussed and the possible substitutes for
      prospective randomized controlled studies in clinical surgery are explored. It is
      concluded that there are defensible and scientific ways to introduce surgical
      innovation even where the 'gold standard' of a prospective randomized controlled
      trial cannot be met.

PMID- 18639056
TI  - False positive diagnosis of subarachnoid haemorrhage on computed tomography scan.
AB  - Five cases are presented in which subarachnoid haemorrhage (SAH) was diagnosed by
      clinicians and/or radiologists on computed tomography (CT) scan. No macroscopic
      SAH was present on neuropathologic examination. In retrospect it was considered
      that the neurologic signs and the neuropathologic features close to the time of
      CT scan were in keeping with the patients being brain dead, i.e. had no cerebral
      blood flow at the time of the scans. On review of the CT scans it was considered
      the hyperdense material seen in the subarachnoid space must have been blood in
      congested subarachnoid blood vessels. The cases demonstrate that if a patient
      presents comatose and CT scan shows cerebral oedema then the presence of high
      attenuation material in the subarachnoid space should not necessarily be
      considered to represent SAH. The value of seeking radiological opinion is
      highlighted but even then diagnosis may be difficult.

PMID- 18639057
TI  - Role of 3D-TOF magnetic resonance angiography for intracranial meningioma.
AB  - Three-dimensional (3D) time of flight (TOF) magnetic resonance angiography (MRA)
      was performed in 13 patients with intracranial meningioma. 3D-TOF unenhanced MRA
      depicted arterial displacement by tumour, and poorly demonstrated the sinuses,
      veins and tumour mass. The direct visualization of the venous abnormalities on 3D
      TOF MRA was improved by the administration of contrast material. 3D-TOF enhanced
      MRA simultaneously depicted tumour enhancement, arterial and/or venous
      displacement, and dural sinus involvement by the tumour, all of which were in
      good agreement with findings on conventional cerebral angiography. However, MRA
      tended to poorly demonstrate the feeding arteries as compared to conventional
      angiography. Our results indicate that multiview 3D-TOF enhanced MRA non
      invasively provides important information about the topographic relationship
      between tumour mass and the surrounding vasculature.

PMID- 18639058
TI  - Orbital neurilemmoma: report of seven cases.
AB  - Neurilemmoma (schwannoma) has a predilection for the head and neck, especially
      the eighth cranial nerve in the cerebellopontine angle. It rarely occurs in the
      orbit, representing only 1% of orbital tumours. We report seven cases. The nerve
      of origin was identifiable in four cases. Two occurred within the inferior
      oblique muscle. Five were treated successfully by anterior or lateral orbitotomy
      without craniotomy and two required a combined cranio-orbitotomy. The majority of
      orbital neurilemmomas occur as discrete intraorbital lesions without intracranial
      extension and can be safely removed via orbitotomy alone.

PMID- 18639059
TI  - Role of coagulopathy in patients with head trauma.
AB  - Coagulation disorders are a well known complication in patients with head
      injuries. A prospective study was undertaken to determine the incidence and
      prognostic value of haemostatic abnormalities in this group of patients. Clotting
      mechanisms in 105 patients with an isolated head injury were evaluated using
      platelet count (PC), prothrombin time (PT), activated partial thromboplastin time
      (APPT), thrombin clotting time (TCT), plasma fibrinogen concentration (Fib),
      level of fibrin-fibrinogen degradation products (FDP) and increased consumptive
      coagulopathy grade (ICCG) in the first 24 h after injury. The clinical severity
      of the head injuries was represented by the post-resuscitation Glasgow coma score
      (GCS) divided into four coma groups (CG). Test results were compared between two
      outcome groups of patients: discharged and dead. The incidence of disseminated
      intravascular coagulation (DIC) by laboratory criteria in the two groups was 12%
      and 38%, respectively. The differences between mean values of the discharged and
      dead patients for GCS, APTT, FDP and ICCG were statistically significant (P <
      0.001). There was a very strong correlation between the GCS and values of the
      FDP, APTT, TCT and ICCG (P < 0.01). Stepwise logistic regression analysis
      demonstrated that GCS, FDP level, and ICCG predicted outcome in 84% of cases.
      Other tests did not provide additional predictive value. We conclude that
      evaluation of coagulation and fibrinolysis in patients with head injuries is not
      only important in identifying the occurrence of coagulopathy, but also useful in
      predicting head injury outcome.

PMID- 18639060
TI  - Postconcussion syndrome following mild head injury: how significant when it is
      work-related?
AB  - Postconcussional complaints are common after mild head injury. These symptoms can
      be so severe that some patients are unable to return to their previous
      employment. The purpose of this study is to investigate how important is work
      related injury as a factor in determining the degree of disability caused by
      postconcussional symptoms. We studied 67 patients suffering from postconcussion
      syndrome after a mild head injury. These patients were divided into two groups,
      work-related injury and non-work-related injury. The results of this study
      demonstrated that the median duration of sick leave and the median amount of
      compensation were significantly higher in the work-related group (8 months vs. 1
      month, P = 0.0007; US$9000 vs. US$500, P = 0.0035, respectively). Only 41% of the
      work-related injured patients returned to work, compared with 85.7% in the
      nonwork-related injury group (P = 0.0022). The results of this study strongly
      suggested that work-related injury is a significant factor in determining the
      degree of disability associated with postconcussion syndrome.

PMID- 18639061
TI  - 3000 head injuries: a prospective study of patients admitted to Brisbane
      neurosurgical units.
AB  - A prospective epidemiological study of 3095 patients with head injury admitted to
      Brisbane neurosurgical units is presented. Falls were the commonest cause of
      injury overall (42%) but traffic accidents were the leading cause of severe head
      injury Glasgow Coma Scale ([GCS] 8 or less) and had a higher mortality (5.6%).
      Outcome was closely related to GCS, presence or absence and type of skull
      fracture, computed tomography (CT) scan findings and age. Overall mortality was
      4.4%. Mortality for mild head injury (GCS 13-15) was 0.4%, moderately severe head
      injury (GCS 9-12) 10.5% and severe head injury (GCS 3-8) 34.5%. The poor outcome
      in old patients who fall and sustain a mild head injury is highlighted. Low risk
      criteria are identified and recommendations regarding admission and management
      policies are made.

PMID- 18639062
TI  - Neurosurgical aspects of sedimentation levels in acute intracerebral haematoma.
AB  - We describe the neurosurgical aspects of sedimentation levels that are rarely
      found in acute intracerebral haematomas (ICH). We had four patients with acute
      ICH whose cerebral computed tomography revealed sedimentation levels. Two
      patients had received thrombolytic therapy for ischaemic heart disease and one
      for ischaemic stroke. Another patient, who was diagnosed later as having a
      coagulation disorder, did not have any medical history on admission. All patients
      had emergency ICH drainage under local anaesthesia. In the immediate
      postoperative period, we observed dramatic improvement in all the patients,
      without surgical complications. The sedimentation level in an ICH should be
      identified as a specific indicator of a coagulation defect and a thorough search
      for possible underlying coagulopathy is warranted. We believe that simple ICH
      drainage should be performed as the haematoma is in a liquid form.

PMID- 18639063
TI  - Primary central nervous system lymphoma: a retrospective study.
AB  - Eleven patients with primary central nervous system lymphoma (PCNSL) proven with
      biopsy between January 1991 and September 1995 were analysed according to the
      location of lesions, pathological studies, treatment and outcome. The ages of
      these patients ranged from 25 to 74 years with an average of 51.4 years. The male
      to female sex ratio was 6 to 5. The most frequent sites of lesions were frontal
      lobes. One patient had only leptomeningeal involvement. All intracranial PCNSL in
      this report arose from B cells; the leptomeningeal PCNSL case was the only one
      which arose from T cells. All patients received chemotherapy with or without
      radiotherapy, except two patients who did not receive any treatment. The results
      of treatment were generally poor. The survival time of patients who died ranged
      from 2.5 months to 45 months with a median of about 12.5 months. If a combined
      treatment is to be considered, the possibility of complications such as
      leucoencephalopathy should be taken in account.

PMID- 18639064
TI  - Positron emission tomography in ischaemic stroke: cerebral perfusion and
      metabolism after stroke onset.
AB  - PET studies were performed in 37 patients up to 1 month after ischaemic stroke to
      observe the relationships between cerebral blood flow (CBF), rate of cerebral
      oxygen metabolism (CMRO(2)) and oxygen extraction fraction (OEF) with time. PET
      findings were classified as misery perfusion (two patients), luxury perfusion (15
      patients), matched hypoperfusion-hypometabolism (17 patients) or normal (nine
      patients). Misery perfusion was seen up to 3 days post-stroke, suggesting an
      extended time window during which at least some tissue may be salvageable. Luxury
      perfusion, an indication of non-nutritional flow, was seen as early as 30 h and
      as late as 23 days, but more commonly between 3 and 7 days. A matched reduction
      of CBF and CMRO(2) was seen during all time periods, but as early as 27 hours.
      Since this was associated with severely impaired CBF, presumably from the onset
      of stroke, it can be assumed that the duration of cerebral tissue survival is
      less than 27 h under these conditions. We inferred that, for maximal tissue
      recovery, therapy will need to be introduced within 27 h after stroke, but that
      at least some potential for recovery exists up to 3 days.

PMID- 18639065
TI  - An audit of carotid endarterectomy for internal carotid artery disease at Dunedin
      Hospital.
AB  - Carotid endarterectomy, mostly for symptomatic internal carotid artery stenosis,
      has been successfully performed in both the vascular and neurological surgery
      units at Dunedin Hospital. This study was performed to compare our results with
      those of the North American Symptomatic Carotid Endarterectomy Trial and the
      European Carotid Surgery Trial. The 30-day perioperative morbidity and mortality
      rate was 4.3% (1.2% < 95% Cl > 7.4%) which compares favourably with an estimated
      upper limit of 5.5% based on recent trial reports. The present study highlights
      the difficulty in modelling local clinical practice on results of major trials
      when standards of patient evaluation and surgical skill may differ from those of
      the large studies. To justify generalization of indications for intervention
      based on the multicentre trials, there must be continual monitoring of local
      surgical results, and standardized use of diagnostic investigations.

PMID- 18639066
TI  - Brain tumours in Ho Chi Minh City.
AB  - A series of 65 intracranial tumours operated on, and followed by, the same
      surgical team during 7 years is presented as a retrospective analysis (1987
      1994). Among these patients, only 38 had a diagnosis based upon computed
      tomography (CT) scan because it was not until 1991 that the first CT scanner was
      set up in Ho Chi Minh City. Many patients were drowsy or comatose prior to
      operation due to lack of specialists' intervention or tardy diagnosis and
      evacuation from remote provincial hospitals. All operations were satisfactory
      despite the lack of many essential instruments. The histological diagnosis
      followed the classification proposed by Zulch KJ.(1) Intratumoural calcification
      has in no case been seen on X-rays or on histological specimens. Operative
      mortality rate was nil. Although not all the patients with malignant tumours
      could be followed up, the data available concerning their survival time and the
      quality of life seems similar to that observed in other reports.

PMID- 18639067
TI  - Role of inhibition in chronic cerebral hypoperfusion.
AB  - Chronic reductions in cerebral blood flow (CBF) of between 25 and 50% maintained
      for 26 weeks impair neuronal function, through a mechanism which is not known,
      but which is now explored. Increased GABAergic synaptic inhibition may play a
      role, as inhibitory interneurons are known to be relatively resistant to acute
      ischaemic insults. The phenomenon of tetanus-induced longterm potentiation (LTP)
      was previously found to be impaired in this setting, and was thus examined in the
      in vitro rat hippocampus in the presence of bicuculline, a specific GABA(A)
      antagonist, to evaluate the role of inhibition in the impairment of LTP in
      chronic cerebral hypoperfusion (CCH). Nine Sprague-Dawley rats aged 8-10 weeks
      had arteriovenous fistulae (AVF) surgically constructed to reduce CBF to between
      25 and 50%. Ten animals were used as age-matched controls. After a further 26
      weeks, 400 mum hippocampal slices were prepared. Tetanic stimulation was used in
      order to attempt to induce LTP. In vitro extracellular field potentials from
      control and AVF slices with 5 x 10(-)6 M bicuculline exposure and subsequent
      tetanic stimulation were compared. There was no statistical difference between
      the responses of the two groups in either scenario (P > 0.05), although LTP was
      in general more difficult to induce (only occurring in 60% of control animals).
      Possible causes of this are discussed. It is concluded that increased GABAergic
      synaptic inhibition does not play a role in impairment of neuronal function seen
      after 26 weeks of non-infarctional CCH.

PMID- 18639068
TI  - Effects of mild whole body hyperthermia on graded focal ischaemia-reperfusion in
      a rat stroke model.
AB  - The influence of body temperature on focal cerebral ischaemia-reperfusion was
      investigated by using a well established rat stroke model. Three different
      degrees of ischaemia were created in the cerebral cortex of the right middle
      cerebral artery territory by varying the duration of clamping of the bilateral
      common carotid arteries and the right middle cerebral artery with full
      reperfusion. Mild hyperthermic (body temperature 38-39 degrees C) influence
      during ischaemia significantly enhanced the severity of infarction in mild (30
      min) ischaemia, mean infarct volume was 78% greater than normothermic (body
      temperature 36.5-37.5 degrees C) group (P < 0.001); and in moderate (60 min)
      ischaemia, mean infarct volume was 23% greater than in the normothermic group (P
      < 0.05); but no difference between the two groups was observed in severe (90 min)
      ischaemia. Our data suggest that mild whole body hyperthermia during focal
      ischaemia-reperfusion has a detrimental effect on the infarct volume only in mild
      and moderate ischaemia in this model.

PMID- 18639069
TI  - En bloc mastoidectomy to avoid postoperative retroauricular deformity in the
      transpetrosal approach.
AB  - The authors describe a surgical technique to avoid postoperative retroauricular
      deformity following the transpetrosal approach. After removing a one-piece
      temporal and suboccipital bone flap, the mastoid process is cut obliquely by
      using a sagittal saw towards an imaginary line drawn from the point on the
      petrous ridge just lateral to the arcuate eminence to the burr hole opened medial
      to the occipital groove. This technique allows en bloc removal of the mastoid
      process without resulting bone defects. Three patients who were treated with this
      technique and followed up for more than 1 year showed good cosmetic results with
      no complications including cerebrospinal fluid leakage. We believe this en bloc
      mastoidectomy offers a definite advantage in regard to avoid postoperative
      retroauricular deformity.

PMID- 18639070
TI  - Unilateral reverse latissimus dorsi muscle flap for postoperative CSF leak and
      wound dehiscence in lumbosacral defects: a lifeboat approach.
AB  - A lumbosacral defect with cerebrospinal fluid (CSF) leak, particularly after
      breakdown of a repaired lipomeningomyelocele, is often a difficult problem to
      manage. Although several methods of local flap coverage have been used, local
      wound infection and tissue cellulitis associated with the wound dehiscence makes
      the repair prone to redehiscence. The associated CSF leak requires a good
      reliable closure as a matter of urgency. We describe two patients with
      lipomeningomyelocele, operated upon for tethered cord syndrome, who developed
      postoperative CSF leak and wound dehiscence. The associated wound infection and
      signs of meningitis made re-exploration, debridement and a dependable, well
      vascularized cover of the dura mandatory. The reverse latissimus dorsi flap
      provided a good vascularized seal. Both patients recovered rapidly.

PMID- 18639071
TI  - Schwannoma of the spinal accessory nerve.
AB  - The authors report a case of a schwannoma originating from the spinal root of the
      accessory nerve. The patient was a 40-year-old woman with chronic headache and
      blurred vision. A neurological examination failed to reveal any abnormal findings
      except for papilloedema. A computed tomographic (CT) scan showed hydrocephalus
      and a magnetic resonance image (MRI) on admission showed an enhancing
      extramedullary tumour located at the level of foramen magnum. The tumour was
      successfully removed and was verified to originate from the spinal root of the
      right accessory nerve. The hydrocephalus improved soon after surgery. The patient
      left hospital in a satisfactory condition. There are 15 cases of accessory nerve
      schwannomas reported in the literature; the authors report the 16th. Although
      accessory nerve schwannoma is very rare, one should consider it as one of the
      differential diagnoses for tumours at the foramen magnum.

PMID- 18639072
TI  - Multiple basilar trunk aneurysms and bilateral internal carotid artery
      hypoplasia.
AB  - We describe a case of a 32-year-old woman with bilateral hypoplastic internal
      carotid arteries who presented with subarachnoid haemorrhage and was found to
      have two basilar trunk aneurysms. Carotid angiography showed that both internal
      carotid arteries were narrowed at their origin and terminated at the cervical
      segment. Vertebral angiography demonstrated a dilated vertebrobasilar system
      which supplied sufficient blood flow for both cerebral hemispheres through the
      posterior communicating arteries. The patient was successfully treated by
      multiple operations.

PMID- 18639073
TI  - Sacral hydatid cysts with intrapelvic extension presenting as herniated
      intervertebral disc.
AB  - Hydatid disease of bone is a rare condition. Although the bones most often
      involved are the vertebrae, sacral vertebral involvement is extremely rare.
      Prognosis is poor despite extensive medical and surgical treatment. In this paper
      we present two unusual cases of hydatid disease located in the sacral vertebrae
      with extension into the pelvic cavity causing radicular symptoms.

PMID- 18639074
TI  - Traumatic Korsakoff syndrome.
AB  - A case of Korsakoff's syndrome occurring after a fall is reported. The patient
      was comatose on admission. Cerebral contusions were seen in the frontal lobes
      bilaterally, left temporal lobe, right caudate nucleus and cerebellar vermis.
      Cerebral blood flow (CBF) study showed diffuse hyperaemia. Although his conscious
      state improved gradually, he showed disorientation, antegrate and retrograde
      amnesia and confabulation 2.5 months later and was diagnosed as having
      Korsakoff's syndrome. Magnetic resonance imaging (MRI) and CBF studies during
      this period showed damage in the midbrain and general hypoperfusion. He recovered
      gradually, confabulation disappeared but a mild memory disturbance remained;
      hypoperfusion on CBF studies also improved up to the normal range. Among the
      limbic diencephalic structures, the frontal lobes were thought to be involved
      most prominently in this case of Korsakoff syndrome.

PMID- 18639075
TI  - Non-union after a two-level anterior cervical decompression and fusion with
      Surgibonetrade mark.
AB  - Numerous alternative implants have been proposed for cervical fusion, including
      bovine bone. We report a case of a two level cervical interbody fusion for
      degenerative disc disease using bovine dowels of Unilab Surgibonetrade mark. We
      describe the clinical evolution and histological examination after failure of the
      procedure due to non-union of the Surgibone implants. Alternative grafting
      substitutes are discussed with respect to their immunological, cytotoxic and
      osteoinductive aspects. Based on a literature review we conclude that allografts
      have a significantly better cytological biocompatibility than Surgibonetrade mark
      and allow a higher fusion rate. The ideal graft remains autologous bone.

PMID- 18639076
TI  - Primary multiple hydatid cysts localizing in the petroclival area.
AB  - Hydatid cyst of the posterior fossa is very rare. In this report we present a 22
      year-old female who had primary multiple hydatid cysts localizing in the
      petroclival areas. The report is noteworthy because of the unusual location, and
      the cranial and spinal dissemination of cysts despite previous treatment.

PMID- 18639077
TI  - Sacral intradural myolipoma causing tethered cord syndrome.
AB  - We report a case of tethered cord syndrome caused by a sacral myolipoma. The
      patient was a 12-year-old girl who had a smooth surfaced, cord-like mass in the
      sacral area; it tethered the conus medullaris at the S1-2 level and extended from
      there to the left S3-4 intervertebral foramen, involving the left S3 root. The
      condition was relieved by surgical removal of the tumour and the neurological
      symptoms were alleviated. Pathological study disclosed that the mass was a
      myolipoma. Discussion about the origin of the myolipoma is made with references
      hitherto reported.

PMID- 18639078
TI  - Dysembryoplastic neuroepithelial tumour as a cause of coma.
AB  - Dysembryoplastic neuroepithelial tumour (DNT), a non-evolutive intracranial
      cortical lesion, is generally associated with epileptic seizures principally
      among youths. A case of a DNT which presented with uncommon clinical features,
      characterized by severe intracranial hypertension and progressive blindness
      warranting emergency surgery, is documented. In addition to the classical
      radiological and neuropathological features characteristic of DNTs there was a
      large haemorrhagic cystic haematoma as a result of repeated dissections and/or
      ruptures of the abnormal vessels in areas, explaining some of the atypical
      clinical symptoms. Therefore the need for a regular, careful clinical and
      radiological follow-up of cases with cystic DNTs is strongly recommended.

PMID- 18639079
TI  - Chronic intracranial hypotension.
AB  - Acute intracranial hypotension can occur following lumbar puncture or a fall, and
      sometimes spontaneously. Most cases resolve within weeks or months but some
      require surgical repair of the defect causing leakage of cerebrospinal fluid
      (CSF). It is conceivable that such leaks could become chronic if the defect is
      incompletely sealed. We report the case of a 49-year-old male who presented with
      a 10-month history of headache associated with a leaking thoracic extradural
      arachnoid cyst. After this was repaired he reported relief not only of his recent
      headaches but also of chronic alcohol-related headaches. A long-standing anaemia
      resolved and tinnitus hyperacusis improved. It is suggested that an injury 30
      years before may have initiated the leak of CSF resulting in chronic intracranial
      hypotension.

PMID- 18639080
TI  - Endoscopic treatment of spinal epidural hematoma.
AB  - We report the use of a spinal endoscope via a limited cervical laminotomy to
      evacuate a spinal epidural hematoma. The patient was a 75-year-old male with a 32
      year history of ankylosing spondylitis. Following a low speed motor vehicle
      accident he developed a cervicothoracic epidural hematoma without an associated
      fracture. Despite a rapidly improving neurological state, his rapidly
      deteriorating cardiorespiratory state required systemic anticoagulation
      necessitating decompression of the hematoma. The hematoma was successfully
      removed via a limited C6 and C7 laminotomy using the endoscope and a malleable
      disposable aspirator. We conclude that epidural hematomas can be readily
      evacuated via endoscopic techniques without extensive laminectomy. This technique
      may be used for approaching intraspinal pathology in high risk patients where
      extensive exposure may be contraindicated.

PMID- 18639081
TI  - Pseudoaneurysm of anterior communicating artery following transsphenoidal surgery
      for craniopharyngioma.
AB  - Fusiform dilatation and pseudoaneurysm formation in arteries of the circle of
      Willis has been reported as a complication following surgery for
      craniopharyngiomas through craniotomies. We present a case of anterior
      communicating artery pseudoaneurysm following transsphenoidal surgery for
      craniopharygioma in an adult.

PMID- 18639082
TI  - Mobile epidermoid tumours of the lumbar spinal canal.
AB  - A case of a 19-year-old female with a mobile epidermoid tumour in the lumbar
      spinal canal is reported. Magnetic resonance images taken twice before surgery
      revealed movement of the tumour from L2 to L1-2 in a 2-week interval. At surgery
      the tumour, which was shiny and fragile, was totally removed and the pain
      disappeared after surgery. This is the first reported case of a mobile epidermoid
      tumour in the lumbar region.

PMID- 18639083
TI  - Cerebral primitive neuroectodermal tumour in an elderly patient with long-term
      survival.
AB  - Primitive neuroectodermal tumours (PNET) in the cerebral hemispheres
      predominantly occur in early life. The mean survival from the time of diagnosis
      is approximately 8 months. Only 18 cases in patients older than 15 years have
      been described. There have been no cases of PNET in a patient older than 65
      years. We describe a case of PNET in a 69-year-old man without recurrence 30
      months postoperatively following radiotherapy and carboplatin chemotherapy.

PMID- 18639084
TI  - Cerebral air embolism due to disconnection of a central venous catheter.
AB  - A case of cerebral air embolism complicating disconnection of a central venous
      catheter is presented. In the context of increasing use of central venous
      catheterization this case highlights the risk of cerebral air embolism associated
      with the use of central venous catheters. In this case there was no patent
      foramen ovale and air must have passed from the venous to the cerebral
      circulation through physiologic shunts in the lung. Possible means of entry of
      air with central venous catheters, pathogenetic mechanisms relating to cerebral
      air embolism, treatment and preventative measures are also discussed.

PMID- 18639085
TI  - Ataxia telangiectasia with long survival.
AB  - A few patients with ataxia telangiectasia survive into the 3rd decade. In the
      central nervous system, dilated meningeal veins have been noted in a few cases
      but as a rule the vasculature in both brain and spinal cord appears normal. We
      present the case of the longest reported surviving patient with ataxia
      telangiectasia who died at the age of 34 years and showed numerous vascular
      malformations with gliosis and haemosiderin in the cerebral white matter and
      spinal cord. These are similar to the features described in three previously
      reported long surviving cases of ataxia telangiectasia. In addition, however,
      numerous corpora amylacea were present, a finding not previously described. Also
      presented is the magnetic resonance imaging (MRI) scan which was of diagnostic
      value; there have been very few MRI scans recorded in ataxia telangiectasia. It
      showed lesions consistent with vascular malformations in cerebral white matter
      with surrounding abnormal tissue consistent with gliosis. Gross cerebellar
      atrophy was also demonstrated. It is significant that MRI scans 6 months apart at
      the age of 32 years showed progression of the lesions.

PMID- 18639086
TI  - Transsphenoidal microsurgical removal of large pituitary adenomas.

PMID- 18639087
TI  - Helper component for aphid transmission encoded by region II of cauliflower
      mosaic virus DNA.
AB  - A deletion mutant of cauliflower mosaic virus (CaMV) isolate NY8153 deficient in
      aphid transmissibility was constructed by BAL-31 exonuclease treatment of XhoI
      linearized pCMS31 (a plasmid containing the entire CaMV genome cloned in the SalI
      site of pBR322), followed by ligation. The resulting mutant, pSA103, lacked about
      100 by from the putative protein-coding region II of CaMV DNA. In turnips there
      was no difference in the number and appearance of starch lesions or hybridization
      lesions, or in the nature of symptoms in systemically infected leaves induced by
      pSA103 DNA, pCMS31 DNA, and NY8153 DNA. Systemic symptoms appeared later in
      plants infected with pSA103 (27 +/- 2 days) than in those infected with the
      parental pCMS31 DNA (19 +/- 2 days). Aphids fed on virus SA103-infected mustard
      plants were unable to transmit the virus to healthy plants while 30-70%
      transmission was observed from plants infected by the parent virus. Virions
      extracted from turnips infected with the mutant had DNA still containing the
      deletion. In addition, the single-stranded discontinuity in region II of NY8153
      DNA was missing in this DNA. The results suggest that region II codes for a
      "helper component" required for aphid transmission of CaMV.

PMID- 18639088
TI  - Subassembly aggregates of papaya mosaic virus protein.
AB  - An examination of the number of subunits in small aggregates of papaya mosaic
      virus (PMV) coat protein is presented based on a model system which gives results
      consistent with the experimental observation that the 14 S subassembly species is
      a double disc, composed of two rows of nine subunits each. The estimated
      hydration of the disc, about 0.85 g 1H20/9 protein, is unusually large and
      indicates a cavitated structure for the disc. Comparison with other rod-shaped
      viruses suggests that the flexuous nature of PMV is a consequence of sparse axial
      inter-subunit contacts at high radius.

PMID- 18639089
TI  - Endovascular and surgical treatment of a metameric spinal arteriovenous
      malformation.
AB  - Metameric spinal arteriovenous malformations (AVMs) refer to the lesions
      completely outside of the spinal cord and the surrounding dura. This paper
      presents an unusual metameric spinal AVM that was fed by multiple
      radiculomeningeal arteries and was located totally within the extradural space
      and the vertebral bodies. The metameric spinal AVM has an exclusive epidural
      venous drainage and presents as a distinct mass from the dural and the intradural
      spinal AVMs. Total removal of metameric spinal AVMs are sometimes difficult
      because of wide extension, profound bleeding, and spinal instability after
      resection. Therefore, the basic management strategy for these lesions is
      preoperative arterial or venous embolization and resection.

PMID- 18639090
TI  - Long-term follow-up of craniovertebral junction arteriovenous fistulas surgically
      treated by feeder obliteration: report of three cases.
AB  - Craniovertebral junction arteriovenous fistulas are still rare and are viewed
      differently from other arteriovenous fistulas because of their specificity of
      location and treatment. Intravascular treatment has come to play an important
      role in this area, but it is still controversial in terms of safety and
      reliability for complete obliteration. From the anatomical point of view, direct
      surgery seems to be more efficient and safe than endovascular therapy based on
      our experience with three surgically treated cases. In all three cases, the
      surgical approach was intended to obliterate the feeders in the vicinity of the
      nidus. In 2 of 3 cases, follow-up angiography showed complete obliteration of the
      fistulas and one case showed partial obliteration. No recurrence of symptoms was
      encountered 4-7 years postoperatively. Surgical treatment is still advantageous
      over intravascular treatment in this type of arteriovenous malformation. Simple
      surgical fistulous obliteration may lead to the gradual complete disappearance of
      this malformation.

PMID- 18639091
TI  - Spinal arteriovenous malformations: a personal review.
AB  - This is a review of my personal series of 76 operated cases of spinal
      arteriovenous malformations. The anatomy of the lesions in my series is compared
      to other large series, including the National Institutes of Health study of 81
      cases, Symon's 60 cases, Pia's 161 cases and Berenstein's 81 cases. My personal
      opinions regarding the etiology and pathophysiology of these lesions is
      presented. My progressive changes in approach to diagnosis and treatment over the
      25-year period are reviewed, as are the results.

PMID- 18639092
TI  - Functional prognosis after treatment of spinal dural arteriovenous fistulas.
AB  - We statistically evaluated the functional outcome after surgery or embolization
      therapy of 43 patients with spinal dural arteriovenous fistula including 10
      patients of our own and 33 previously reported cases in the literature. This
      study prompted us to consider that a patient under 70 years old who is treated
      within 2 years 6 months after the onset of symptoms and whose gait or urinary
      disturbance is slight or moderate without absence of deep tendon reflexes in the
      lower extremities is expected to get a good functional prognosis after treatment.

PMID- 18639093
TI  - Treatment strategy of spinal arteriovenous malformations based on a simple
      classification.
AB  - We propose a treatment strategy of the spinal arteriovenous malformation (AVM)
      based on a simple classification. This classification includes three types: dural
      arteriovenous fistula (AVF), perimedullary AVF and intramedullary AVM. Dural AVF
      has its shunt at the dura and can be treated with either surgery or embolization
      with liquid adhesive. Perimedullary AVF has shunt on the spinal cord surface and
      it can be subcategorized into types 1-3 depending on the size of vascular
      pedicles. Types 1 and 2 are treated with surgery, type 3 by balloon or coil
      embolization. Intramedullary AVM has its nidus in the cord and is difficult to
      treat either by surgery or endovascular technique.

PMID- 18639094
TI  - Cavernous angiomas of the brain stem and spinal cord.
AB  - This article reviews the pathology, clinical course and management of cavernous
      angiomas in the brain stem and spinal cord. Both lesions have been diagnosed with
      increasing frequency as a result of magnetic resonance image scanning. Brain stem
      lesions tend to present dramatically; their treatment remains microsurgical
      excision despite some studies that have looked at the use of radiosurgery. Spinal
      lesions are either extra-, or more commonly, intramedullary. Intramedullary
      cavernomas present with a wide spectrum of symptoms ranging from acute
      haematomyelia to presentations that mimic demylelinating conditions;
      extramedullary cavernous angiomas tend to produce radicular symptoms or
      subarachnoid haemorrhage. Both are treated by microsurgical excision.

PMID- 18639095
TI  - Natural history of arteriovenous malformations: analysis of non-radically treated
      patients.
AB  - The natural history of cerebral arteriovenous malformations (AVMs) was studied in
      115 patients with untreated or incompletely obliterated AVM. Sixty-six patients
      had histories of hemorrhage, 20 had seizures, 18 had progressive ischemic
      neurologic deficits and 8 had headache. Three patients had no symptoms
      attributable to the AVM. Twenty-seven (23%) AVMs rebled or newly bled and the
      cumulative bleeding or rebleeding rate was 72.5% (4.2% per year). The cumulative
      bleeding rate of the neurologic deficit group, however, was significantly lower
      than the cumulative rebleeding rate of the hemorrhagic group (P < 0.05) and that
      of the seizure group (P < 0.05). No significant differences were found in regard
      to the initial clinical manifestations. The cumulative survival rate was 84% and
      the average mortality rate was 1.4% per year. Fifty patients (43%) were below 90
      in Karnofsky's Index at the end of the follow-up period and the average morbidity
      rate was 6.0% per year.

PMID- 18639096
TI  - Normal perfusion pressure hyperperfusion in cerebral arteriovenous malformation
      surgery: model study on the hemodynamics and mechanisms.
AB  - A simulation study was undertaken using a compartmental flow model of a large
      high-flow cerebral arteriovenous malformation to investigate the hemodynamic
      changes during obliteration procedures. Under certain autoregulatory conditions,
      marked hyperperfusion (92 ml/100 g/min) could be induced in association with
      increased wall stress of the arterioles. Narrowing of the autoregulatory pressure
      range and its shift to a low pressure level are suspected to be among the
      possible causes of normal perfusion pressure breakthrough phenomenon.

PMID- 18639097
TI  - Diagnosis of cerebral arteriovenous malformations with three-dimensional CT
      angiography.
AB  - High speed spiral computed tomography (CT) is well known to be a good tool to
      visualize cerebrovascular lesions; this technique is called three-dimensional CT
      angiography (3D-CTA). Although 3D-CTA is widely accepted to diagnose cerebral
      aneurysms because it is less invasive and more useful than digital subtraction
      angiography, little is known about its diagnostic potential for arteriovenous
      malformation (AVM). In this study, the efficacy of 3D-CTA in diagnosis and
      surgical planning was investigated in 21 patients with AVMs. AVMs located in the
      cerebral hemisphere, the cerebellum, the basal ganglia, the brain stem, the
      corpus callosum, the optic chiasm and the lateral ventricle. 3D-CTA clearly
      demonstrated the three-dimensional feature of the feeding artery, the nidus, the
      draining vein and the surrounding normal structures. We conclude that 3D-CTA is
      essential to preoperative planning for the appropriate surgical approach toward
      the AVM.

PMID- 18639098
TI  - Intraoperative non-invasive infrared imaging during resection of large
      arteriovenous malformations.
AB  - Intraoperative infrared (IR) imaging during resection of arteriovenous
      malformations (AVMs) is presented. The IR images obtained by the IR camera
      installed on the operating microscope realizes a non-invasive observation of the
      temperature distribution map on the cortex. By adjusting the window width and
      level of the IR images, the surface temperature between cerebral arteries,
      cerebral veins and cortex were differentiated. Computed colour-coded IR imaging
      represented the cerebral arteries as red, the cerebral veins as blue and the
      cerebral cortex as black. In colour-coded IR imaging, the nidus and draining
      veins of the AVM were demonstrated as red areas on black cortex. Based on
      intraoperative IR images, total obliteration of the feeding arteries could be
      confirmed as normalization of the surface temperature of the nidus and the
      draining veins.

PMID- 18639099
TI  - Clinico-pathological study in patients with transverse-sigmoid sinus dural
      arteriovenous malformations.
AB  - Treatment modalities and histopathological findings of transverse-sigmoid sinus
      dural arteriovenous malformations (AVMs) were evaluated. Twenty-eight patients
      with this disease were treated with a variety of treatment modalities. Ten
      patients were treated surgically. Of these patients, 3 were treated with sinus
      isolation, 4 with sinus removal and 3 with palliative operation. Ten patients
      underwent endovascular surgery. Of these patients, 3 were treated with
      transarterial embolization (TAE) alone, 2 with transvenous embolization (TVE)
      alone and 5 with direct sinus packing (DSP) with/without TAE and/or TVE. Eight
      patients were treated conservatively. The resected dural sinuses were cut into
      serial sections and evaluated histopathologically. The histopathological study
      revealed the communications between dural arteries and dural veins emptying the
      involved sinus. No direct communication between dural arteries and the sinus
      lumen was found. The essential lesion of the dural AVMs was confirmed to be the
      dural AV fistulas within the sinus wall. Transvenous or direct sinus packing may
      well offer a radical and safer alternative to the surgical treatment, but still
      requires a long-term follow-up.

PMID- 18639100
TI  - Newly synthesized liquid embolization material for arteriovenous malformation.

PMID- 18639101
TI  - Disrupted and migrated microcatheter in the vertebrobasilar artery system in
      endovascular embolization of cerebellar AVM: failure of endovascular and
      microneurosurgical retrieval.
AB  - Microcatheter disruption and migration is a rare etiology of complications that
      is directly attributable to preoperative embolization of arteriovenous
      malformations (AVMs). A 16-year-old male presented with cerebellar hemorrhage.
      Angiography showed an AVM in the right cerebellar hemisphere fed by the posterior
      inferior cerebellar artery (PICA) and superior cerebellar artery (SCA). During
      the procedures of preoperative embolization, a microcatheter was spontaneously
      disrupted before N-butyl-2-cyanoacrylate (NBCA) injection. The catheter migrated
      13 cm into PICA, basilar artery (BA) and posterior cerebral artery (PCA). An
      attempt to retrieve the microcatheter by an endovascular procedure was not
      successful. Then, we attempted to pull out the microcatheter though an
      arteriotomy made in the PICA, after completion of AVM extirpation by suboccipital
      craniotomy. At the point of 6-cm retrieval the catheter was disrupted so that 7
      cm of catheter was retained in PICA, BA and PCA. The patient returned to school
      with no neurological deficits. The long-term thromboembolic or toxic effects of
      migrated microcatheter into vertebrobasilar arterial system in this young patient
      should be carefully followed up.

PMID- 18639102
TI  - Total removal of arteriovenous malformations with preoperative embolization and
      intraoperative digital subtraction angiography.
AB  - Between 1991 and 1995 we totally removed 24 cerebral arteriovenous malformations
      (AVMs), employing preoperative embolization in 9 patients and intraoperative
      digital subtraction angiography (DSA) in all 24. There was 1 patient with
      Spetzler grade I lesion, 6 with grade II, 9 with grade III, 5 with grade IV and 3
      with grade V. Nine patients with large AVMs underwent preoperative embolization
      to occlude surgically inaccessible feeders and to reduce arterial blood supply by
      50%. Surgery was performed 3-11 days after embolization. Twenty-one patients did
      well. One patient died of postoperative bleeding complications, and a mild
      neurological deficit appeared in 2 patients. We believe that intraoperative DSA
      is essential for the total removal of cerebral AVMs. The operative mortality and
      morbidity rates could be reduced with preoperative embolization of large AVMs.

PMID- 18639103
TI  - Endovascular embolization of cerebral AVMs prior to surgery or radiosurgery.
AB  - We studied 18 patients with cerebral arteriovenous malformations (AVM) who
      underwent embolization prior to surgery or radiosurgery. Two patients were cured
      with total occlusion of the AVM by embolization alone. Successful size reduction
      of the nidus in the range of 60-99% was obtained in all the other patients.
      Twelve patients underwent the radiosurgery following the embolization, one of
      whom obtained a complete cure. The AVMs in four patients were totally removed
      after the embolization. Although the purpose of embolization of AVMs is to reduce
      AVM size and shunt flow, the strategy of the embolization should be adjusted
      according to the treatment that is to follow, i.e. radiosurgery or surgery. We
      believe that peripheral nidi must be embolized prior to the radiosurgery, while
      deep-sited feeders must be embolized along with main feeders prior to the
      surgery.

PMID- 18639104
TI  - Treatment of unruptured arteriovenous malformations in the brain.
AB  - Clinical features and treatment results of 33 patients with unruptured
      arteriovenous malformations (AVMs) were evaluated. Nine AVMs were located in the
      frontal lobe, 8 in the motor cortex, 5 in the parietal lobe, 6 in the temporal
      lobe, 2 in the occipital lobe and 3 in other parts of the brain. Nine patients
      were treated with microsurgery and 24 with radiosurgery. Total extirpation of the
      AVM was performed in all 9 microsurgery patients. One patient with an AVM in the
      motor cortex experienced upper extremity weakness postoperatively. Eleven of 24
      patients treated with radiosurgery had follow-up imaging studies. Obliteration
      was obtained in 8 patients and decreased size in 3. Complications included 1
      patient with a hemiparesis and 1 with an AVM rupture prior to obliteration. The
      remaining 13 patients did not experience any complications over a mean period of
      21.2 months. Microsurgery appears to be the best treatment for unruptured AVMs in
      non-eloquent areas. Radiosurgery is a safe, effective treatment for unruptured
      AVMs in eloquent areas, although a bleeding risk remains during the latency
      period prior to obliteration.

PMID- 18639105
TI  - Treatment selection for cerebral arteriovenous malformations: radiosurgery or
      microsurgery.
AB  - The clinical results and patient characteristics of 318 cases of cerebral
      arteriovenous malformations (AVMs) were analyzed: 138 patients were treated by
      surgery including 98 cases of total removal and 17 cases of subtotal removal; 37
      patients were treated conservatively; 139 patients were treated by gamma-knife
      and 6 patients were treated by linac-knife radiosurgery using stereotactic multi
      converging arcs systems. Clinical data analysis was performed using the same
      protocol in both of the surgery and the radiosurgery groups. Operative mortality
      for total removal was one out of 98 cases (1%). There was one death by
      hemorrhage, one case of symptomatic rebleeding and two cases of asymptomatic
      bleeding in patients treated by radiosurgery. Thus, mortality was 1 out of 145
      (0.7%). Patients with total resection of AVMs had the best clinical results in
      comparison with subtotal resection or with conservative treatment. Morbidity was
      the lowest in the patients treated by radiosurgery. However, the total
      obliteration rate was lower than the surgical cure rate. The decision for
      treatment should be based on an estimation of mortality, morbidity and cure rate
      for each treatment.

PMID- 18639106
TI  - Radiosurgery for arteriovenous malformations with gamma-knife: a multivariate
      analysis of factors influencing the complete obliteration rate.
AB  - Seventy-two patients with arteriovenous malformations (AVMs) were treated with
      gamma-knife and subsequently analyzed to determine what factors influenced the
      obliteration of AVMs. The volume of nidi ranged from 0.3 to 21.7 ml (mean 3.9 ml)
      and the marginal dose ranged from 9 to 31.5 Gy (mean 21.4 Gy). The cumulative
      obliteration rates of all cases were 41% at 2 years, 67% at 3 years, and 89% at 4
      years. Multivariate analysis demonstrated that only the two variables of flow
      rate (P = 0.020) and dose planning with axial MRI (P = 0.045) had correlation
      with the obliteration rate. Other variables such as size, marginal dose, and
      embolization had no statistical correlation with the obliteration rate. It may be
      very important to evaluate the AVM flow rate to predict the effect of gamma-knife
      radiosurgery on AVMs, even when the nidi volumes are small.

PMID- 18639107
TI  - Successful resection of AVMs on eloquent areas diagnosed by surface anatomy
      scanning and motor-evoked potential.

PMID- 18639108
TI  - Intentionally staged operation for large and high-flow cerebral arteriovenous
      malformation.
AB  - This paper describes two cases of large and high-flow cerebral arteriovenous
      malformations (AVMs) which were successfully treated by intentionally staged
      operations. During dissection of the nidus, uncontrollable bleeding from the
      nidus and surrounding brain tissue was encountered in both cases, and staged
      operations were attempted. The isolated remaining nidus and the main draining
      vein were thoroughly covered with a non-adhesive material (Gelfilm(R)) to prevent
      adhesion. We performed cerebral angiography before the second operation. In both
      cases, the extent of size-reduction of the remaining nidus on angiography was
      more than that of the actual preparation in the first operation due to
      thrombosis. Intentionally staged surgery for a large and high-flow AVM is
      beneficial because it prevents 'normal perfusion pressure breakthrough' or
      'overload phenomenon', which is one of the factors affecting the patient's
      prognosis. For the subsequent operation, it is beneficial to use the non-adhesive
      material to prevent adhesion between remaining nidus and surrounding brain
      tissue. It is a safer procedure for the total removal of the remaining nidus. It
      is also important to perform the angiography before the second operation. Precise
      analysis of the the extent of remaining nidus before the second operation enables
      preparation of appropriate surgical strategies.

PMID- 18639109
TI  - Staged surgery for a large cerebral arteriovenous malformation to prevent the
      overload phenomenon.
AB  - Intracerebral hemorrhage and/or edema is a sequel following removal of a large
      nidus. We call the vascular load an 'overload phenomenon'. To prevent it by
      stepwise reduction of the nidus size, staged surgery is recommended for a large
      AVM (nidus size of more than 5 cm). With the recent advancement of the
      intravascular technique, preoperative embolization is also a good option to
      reduce the nidus size resulting in a prevention of the overload phenomenon and a
      reduction in intraoperative bleeding. The overload phenomenon is visualized on
      the immediate postoperative angiogram as 'modja-modja' (stagnating and shaggy)
      vessels around the removed nidus, which disappear in a month. We present a case
      in which those vessels were identified. Maintaining the postoperative blood
      pressure at 80 to 100 mmHg is also essential for preventing the overload
      phenomenon prior to staged surgery and/or preoperative embolization.

PMID- 18639110
TI  - Surgical treatment of pericentral arteriovenous malformation.
AB  - Surgical treatment of pericentral arteriovenous malformation (AVM) near the
      central sulcus is discussed. Thirty-four patients with pericentral AVM were
      treated and they can be classified into four subtypes: operculofrontal AVM (nine
      cases); dorsolateral AVM (nine cases); parasagittal AVM (11 cases); and giant AVM
      involving sensorimotor cortices (five cases). In all surgically treated patients
      with operculofrontal AVM or dorsolateral AVM, nidi were totally removed and
      permanent morbidity was 6%. On the other hand, complete obliteration was usually
      difficult for parasagittal AVMs. Among six patients with surgically-treated
      parasagittal AVM, transient paralysis was found in three (50%) and permanent
      morbidity was observed in one (17%). Among four patients with parasagittal AVM
      who were treated by embolization therapy alone, transient paralysis was found in
      three (75%) and permanent morbidity was recognized in two cases (50%).

PMID- 18639111
TI  - Improved technique for liquid embolization of cerebral arteriovenous
      malformation: catheter-tip position and flow control.
AB  - This paper outlines the problems currently limiting the success and safety of
      embolization of cerebral arteriovenous malformations (AVMs) based upon the
      experiences of 110 cases. In cases where liquid embolic material was deposited
      mainly in arterial feeders, there was a reconstitution of the nidus through
      residual primary feeders and recruitment of blood flow via collateral tracts. A
      recent improvement of flexible microcatheters with minimal friction has made it
      possible to place the tip of a microcatheter into the nidus with greater success
      and safety. In order to obtain better filling of the AVM nidus and slower
      penetration to the draining veins, it is important to perform a temporary balloon
      occlusion of another main feeding pedicle to reverse the dynamic balance in favor
      of the pedicle being injected. In order to successfully occlude arteriovenous
      shunts in the nidus, appropriate flow control and optimal setting time of n-butyl
      2 cyanoacrylate have prime importance.

PMID- 18639112
TI  - Clinical outcome of radiosurgery, embolization and microsurgery for AVMs in the
      thalamus and basal ganglia.
AB  - Ninety-six cases of arteriovenous malformation (AVM) in the basal ganglia and
      thalamus were retrospectively analyzed. The prognosis of patients presenting with
      hemorrhage was poor, if conservatively treated. The mortality and morbidity were
      62.5% and 12.5%, respectively. In the surgically resected group, 10 (66.6%) out
      of 15 patients are working and 4 patients (26.7%) are independent. Only one
      patient, who had a hypertensive intracerebral hemorrhage during rehabilitation,
      is bed-ridden. As to the final outcome of 60 cases treated with the gamma knife,
      39 patients (65%) are working, 11 patients (18.3%) are independent and 4 patients
      (6.7%) are dependent. Comparing the treatment results between pre- and post-gamma
      knife era, extirpation rate, morbidity and mortality were 44.8%, 20.7% and 20.7%
      in the pre-gamma-knife era, while those in the post-gamma-knife era were 80.0%,
      10.4% and 1.5%, respectively. Thus, the final outcome has undoubtedly improved
      after the introduction of the gamma-knife.

PMID- 18639113
TI  - Minimally invasive surgery for cerebral AVM in the eloquent cortex.
AB  - The treatment of arteriovenous malformation (AVM) is still a challenging problem
      in the neurosurgical field. The usual operative procedure has been the removal of
      the AVM by sucking the gliosis which surrounds it. However, by using such a
      method in the functional area, especially the sensory and motor cortex, it has
      been impossible to remove the AVM without postoperative neurological deficit.
      Recent reports have shown that a 1 mm thickness of the brain around a large AVM
      is non-functioning;(1,2) therefore, we aimed to remove only the AVM without
      sucking the brain.

PMID- 18639114
TI  - Dissection technique in the surgery of arteriovenous malformations of the brain.
AB  - We present our dissection technique in the surgery of arteriovenous malformations
      of the brain. In the last 3 years, we have used sharp dissection of arachnoid
      tissue with microscissors and dissection of the nidus without coagulation
      procedures that have not been discussed in the literature. Using these
      techniques, we performed total resection in 28 patients. The outcomes were highly
      satisfactory among these patients: no mortality and only one major morbidity. Our
      results indicate the effectiveness of our resection method.

PMID- 18639115
TI  - Removal of the N-terminal part of alfalfa mosaic virus coat protein interferes
      with the specific binding to RNA 1 and genome activation.
AB  - Trypsinized coat protein of alfalfa mosaic virus lacking 25 amino acids at its N
      terminus still has the capability to form complexes with RNA which are detectable
      by sedimentation in sucrose gradients. However, it does not protect specific
      sites on the RNA against degradation by ribonuclease, as the native coat protein
      does (D. Zuidema, M. F. A. Bierhuizen, B. J. C. Cornelissen, J. F. Bol, and E. M.
      J. Jaspars (1983) Virology 125, 361-369.). The trypsinized coat protein has lost
      the capacity of the native coat protein to make the genome RNAs of alfalfa mosaic
      virus infectious or to interfere with the infectivity brought about by the native
      coat protein. These findings suggest that genome activation occurs via binding of
      the N-terminal part of the coat protein to specific sites on the RNAs.

PMID- 18639116
TI  - Differences in polyadenylate length between individual barley stripe mosaic virus
      RNA species.
AB  - Barley stripe mosaic virus (BSMV) RNA which has been shown to contain an internal
      polyadenylate sequence (Agranovsky, Dolja, Gorbulev, Kozlov, and Atabekov,
      "Virology", 113, 114-187, 1981; Agranovsky, Dolja, and Atabekov, "Virology," 119,
      51-58, 1982) was resolved into oligo(dT)-cellulose-bound [poly(A)+] and unbound
      [poly(A)-] fractions. Individual RNAs of all strains tested (i.e., those with two
      , three-, or four-components) differentially responded to affinity
      chromatography. Thus, in all cases the poly(A)+ fraction was dramatically
      enriched in RNA 1 whereas RNA 2 was found mostly in the poly(A)- fraction. RNA 3
      was distributed approximately equally between poly(A)+ and poly(A)- fractions.
      The bulk of RNA 4 was in the poly(A)- fraction. The poly(A) length spectra in
      total, poly(A)+, and poly(A)- BSMV RNA fractions were compared. The length of
      poly(A) in total BSMV RNA was 8 to 40 residues. Fragments of 19 to 40 residues
      and probably longer were predominant in the poly(A)+ RNA fraction. The poly(A)-
      fraction contained tracts having not more than approximately 25 adenylate
      residues, with the bulk of the tracts having 12 or fewer residues.

PMID- 18639117
TI  - Chemical and serological comparison of the coat proteins of velvet tobacco mottle
      and Solanum nodiflorum mottle viruses.
AB  - Velvet tobacco mottle virus (VTMoV) and Solanum nodiforum mottle virus (SNMV) are
      serologically closely related as shown by immunodiffusion tests. Dissociated
      VTMoV coat protein separates into three electrophoretic components in
      polyacrylamide gels corresponding to polypeptides with Mr's of about 37,000,
      33,000 and 31,500, whereas SNMV protein migrates as a single component of Mr
      about 31,000. Evidence is presented indicating that the VTMoV particle is built
      from a single species of protein subunit of Mr about 37,000. However, the protein
      is unstable and degrades during virus purification into a stable polypeptide of
      Mr about 31,500. It is proposed that the partially degraded VTMoV particle
      consisting of the stable polypeptide is antigenically similar to the SNMV
      particle and that these two particles with stable protein subunits are the
      principal antigens involved in eliciting antibody production in animals. The
      antigenic and other properties of VTMoV and SNMV are discussed in relation to
      their taxonomic identity.

PMID- 18639118
TI  - Comparison of capsids and nucleocapsids from cowpea mosaic virus-infected cowpea
      protoplasts and seedlings.
AB  - Extracts of Cowpea mosaic virus (CPMV)-infected Cowpea (Vigna unguiculata)
      protoplasts were applied to an anion-exchange agarose resin. Both capsid-like and
      virion-like particles (collectively designated D-VLP) were present in the
      nonabsorbed fraction, although purified capsids and virions from protoplasts and
      from plants were absorbed irreversibly under the same conditions. The larger of
      the two capsid proteins, L protein, behaved similarly during electrophoretic
      analyses regardless of protoplast or plant source. The other capsid protein, S,
      showed decreasing apparent molecular weight and increasing anionic charge when it
      was recovered from (1) D-VLP, (2) virus particles from protoplasts, and (3) virus
      particles from leaf tissue of young infections and (4) older infections of
      plants, in the order indicated. This series of four kinds of particles is
      postulated to be temporal, reflecting the progress of proteolytic processing
      events. The proteolysis affects the carboxyl terminal but not the amino terminal
      sequences of S protein from particles recovered from plants.

PMID- 18639119
TI  - Restriction map and southern analysis of the bean golden mosaic virus genome.
AB  - A restriction map showing 5'-3' polarity for two species of circular single
      stranded (ss) DNA from bean golden mosaic virus (BGMV) is presented. The two
      viral single-stranded DNAs, which are very similar in size, were separated by
      prolonged agarose gel electrophoresis at low voltage. Hybridization analysis
      using probes made from these separated DNAs shows they are largely dissimilar in
      nucleotide sequence except for a common region of high homology which has been
      mapped to a unique location on each species. Molecular clones of BGMV DNA from
      restriction fragments comprising all of one of the two DNAs and part of the other
      were used to confirm the restriction and hybridization analysis. These results
      provide further evidence consistent with the hypothesis that BGMV and other
      geminiviruses possess divided genomes with two components of nearly equal size.

PMID- 18639120
TI  - Primary structure of brome mosaic virus coat protein.
AB  - The amino acid sequence of BMV (brome mosaic virus) coat protein is presented and
      compared with the sequence derived from RNA structure. Apart from removal of the
      N-terminal methionine residue and acetylation of the following serine residue, no
      post-translational modifications occur.

PMID- 18639121
TI  - Traumatic axonal injury in lambs: a model for paediatric axonal damage.
AB  - Axonal injury (AI), an important determinant of clinical outcome after traumatic
      head injury in adults, has been little studied in child neurotrauma. In this
      experimental model, 10 anaesthetised, ventilated and physiologically monitored 4
      5 week old lambs sustained a temporal impact to an unconstrained head.
      Examination of the brain 2 hours post-impact using amyloid precursor protein
      immunostaining, a sensitive marker of axonal damage, revealed widespread
      multifocal AI in the ipsilateral and contralateral hemispheres, brain stem and
      cerebellum in all cases. Impact contusions (predominantly microscopic) (8 10 ),
      contralateral contusions (2 10 ), parenchymal haemorrhage (10 10 ) and focal
      subarachnoid haemorrhage (10 10 ) were also present. Unusual multifocal
      cerebellar granular layer necrosis occurred in all impacted lambs. The pattern of
      AI in these lamb brains 2 hours post-impact was similar to that found in adult
      sheep using the same experimental paradigm.

PMID- 18639122
TI  - Transcranial Doppler assessment of the lower cerebral autoregulatory threshold.
AB  - Continuous transcranial Doppler ultrasonography of the middle cerebral artery
      (TCD-MCA) has been proposed as a method of identifying the lower cerebral
      autoregulatory threshold. This study investigated the relationship between
      continuous TCD-MCA and cerebral blood flow (CBF) in sheep. Arterial blood
      pressure, intracranial pressure, CBF and left TCD-MCA were measured in 12
      anaesthetized and ventilated merino sheep. Cerebral perfusion pressure (CPP) was
      reduced by haemorrhagic hypotension. Measurements were recorded continuously and
      breakpoint thresholds calculated by an analysis of variance. The TCD-MCA systolic
      velocity breakpoint (50 +/- 1.5 mmHg) did not significantly differ from the lower
      limit of autoregulation, identified by the CBF breakpoint (50 +/- 1.8 mmHg). The
      TCD-MCA diastolic velocity breakpoint occurred at a significantly higher level of
      CPP (64 +/- 2 mmHg) (P < 0.01). The relationship between TCD-MCA flow velocity
      and CBF thresholds has been described. Early divergence of flow velocity may
      represent a compensatory mechanism to maintain CBF.

PMID- 18639123
TI  - Magnetic resonance imaging in subacute combined degeneration of the spinal cord.
AB  - We describe the magnetic resonance imaging (MRI) abnormalities in a patient with
      subacute combined degeneration of the spinal cord (vitamin B12-deficient
      myelopathy). T2-weighted images revealed symmetric, high signal abnormalities in
      the posterior columns of the cervical cord, which resolved following recovery
      from the disease. Recognition of this MRI pattern is important because this is
      likely to represent an early, potentially reversible stage of the disease.

PMID- 18639124
TI  - A meningioma of the lateral cerebellomedullary cistern without dural attachment.
AB  - A rare case of a meningioma in the lateral cerebellomedullary cistern without
      dural attachment is reported. The tumor was attached to the choroid plexus out of
      the lateral recess, not in the fourth ventricle. The radiologic findings and
      operative approach differed from those for fourth ventricle meningiomas or
      cerebellopontine angle meningiomas. Magnetic resonance imanging is the most
      helpful preoperative diagnostic study for determining the precise location,
      volume and extent of the lesion and the site of attachment. Care was taken not to
      injure the lower cranial nerves and the tumor was totally removed except for a
      tiny piece which invaded the proximal portion of the posterior inferior
      cerebellar artery.

PMID- 18639125
TI  - Multiple cerebral aneurysms with persistent primitive trigeminal artery.
AB  - We report a patient with a persistent primitive trigeminal artery (PPTA) detected
      incidentally during cerebral angiography for the ruptured aneurysm. Cerebral
      angiography revealed a PPTA and eight anterior circulation cerebral aneurysms.
      Although cerebrovascular fragility, hemodynamic stress and hypertension are well
      known as etiologic factors for development of cerebral aneurysms, there is a
      known association of aneurysms with a PPTA, fetal carotid-basilar anastomosis.
      Furthermore, this case is rare from the viewpoint of aneurysm multiplicity.

PMID- 18639126
TI  - Delayed intracerebral haemorrhage after intracranial surgery.
AB  - Intracerebral haemorrhage may occur several hours after intracranial surgery. The
      exact mechanism by which this occurs is still unclear, although prolonged brain
      retraction is considered to be the most responsible factor. In these delayed
      postoperative haematoma cases, serial angiography has never been performed. We
      performed angiographic evaluation in such 12 cases and, in 5 of them, surgical
      evacuation of the haematoma was performed because of life-threatening mass effect
      and the cortical veins and the surrounding cerebral tissues were examined
      histologically. In all cases, angiographically thrombotic difufse occlusion of
      the cortical vein(s) without collateral circulation was observed, and
      histologically there was marked damage to the intima of the vein, remarkable
      macrophage infiltration into the subadventitial spaces, and extensive red cell
      extravasation into the subarachnoid space and brain parenchyma from the maximally
      dilated venules and capillaries. These findings suggest that diffuse intravenous
      thrombosis induced by cortical vein injury and prolonged brain retraction may be
      important causes of unexpected delayed postoperative intracerebral haematoma in
      surgery using the interhemispheric or subtemporal approach.

PMID- 18639127
TI  - Spinal cord changes after the evacuation of a spinal subdural haematoma.
AB  - Spinal subdural haematoma is a rare entity. Only a few cases have been reported,
      mainly in patients with coagulopathies or bleeding diathesis, and also in
      patients undergoing anticoagulant therapy following surgery, trauma, or lumbar
      puncture. Symptoms of spinal cord compression produced by spinal subdural
      haematoma may progress rapidly causing complete and irreversible deficits.
      However, rapid diagnosis and surgical intervention can result in a good
      functional outcome for the patient. We report on a 41-year-old woman with a
      normal coagulation profile who developed a spinal subdural haematoma after a
      minor motor vehicle accident. Although initially asymptomatic, she developed a
      dense quadriparesis over a 36-h period. A magnetic resonance imaging study
      demonstrated a subdural mass compressing the spinal cord, and at surgery a spinal
      subdural haematoma was found. She was discharged to an inpatient rehabilitation
      facility. Follow-up at 1 year showed significant improvement in motor function,
      but absence of posterior column function. A follow-up magnetic resonance study
      demonstrated widening of the spinal cord, advanced myelomalacia and a large,
      central, multi-loculated syrinx.

PMID- 18639128
TI  - Natural killer cell lymphoproliferative disease associated with combined
      peripheral and autonomic neuropathy.
AB  - Natural killer cell proliferation is an uncommon haematological disorder that has
      a number of different clinical manifestations. There have been only two prior
      reports linking this process with neurological disease, both reports describing
      peripheral neuropathy. We report the case of a young man presenting with a short
      history of lethargy, lower limb paraesthesia and marked weight loss who was found
      to have a natural killer cell lymphocytosis and features of both an autonomic and
      a peripheral neuropathy. The patient's clinical features responsed to a
      combination of cytotoxic and immunosuppressive therapy, and the patient is now
      clinically stable with mild ongoing lymphocytosis, diarrhoea and postural
      hypotension. We review the possible pathological link between natural killer
      cells and neurological disease.

PMID- 18639129
TI  - Traumatic middle cerebral artery occlusion from boxing.
AB  - A case of a traumatic middle cerebral artery occlusion resulting from a boxing
      injury is presented. A 22-year-old man, an amateur boxer, was admitted because of
      difficulty in speaking, that had appeared a day after a sparring fight. A
      computed tomographic scan showed low-density areas in the left globus pallidus
      and corona radiata. A carotid angiogram indicated complete occlusion of the left
      middle cerebral artery at its origin and an irregularity and narrowing of the
      left internal carotid artery in its supraclinoid portion. The patient was
      discharged 4 weeks after the admission with some persistent expressive dysphasia
      that diminished during the next month. The clinical features and mechanisms of
      the traumatic middle cerebral artery occlusion are discussed.

PMID- 18639130
TI  - Prolonged survival and pulmonary metastasis after local cure of glioblastoma
      multiforme.
AB  - A 59-year-old woman underwent a frontal lobectomy and irradiation for a
      glioblastoma multiforme, with further craniotomies to drain postoperative
      subdural and extradural infections. She survived for 5 years after the initial
      operation, but died as a result of pulmonary metastatic tumors. At post-mortem
      examination no residual intracranial tumor could be found. The pulmonary tumors
      were metastases from the glioblastoma. Prolonged survival, extraneural metastasis
      and curative local treatment are each uncommon in glioblastoma, but all occurred
      in this patient.

PMID- 18639131
TI  - Reversal of rapid visual loss in a patient with an imaging stable diffuse glioma
      following frontal lobectomy.
AB  - A case of rapid painless visual deterioration without increase in tumor size in a
      patient with a corpus callosum glioma is presented. Visual acuity and fields
      improved following a frontal lobectomy.

PMID- 18639132
TI  - A lesson learned from jugular venous oximetry.
AB  - The authors describe the case of a severely head injured patient whose profound
      cerebral infarction was clearly indicated by prolonged desaturation on jugular
      venous oximetry. Shortly thereafter jugular venous oxygen saturation returned to
      normal stable values and measured within normal limits for the next 24 h. As
      demonstrated by a computed tomography (CT) scan, these values appear to have
      represented a jugular mixture of significant amount of cerebral blood that had
      passed through infarcted tissue and remained highly saturated. This is a very
      graphic example of the misleading influence that regional flow-metabolic
      inhomogeneities can have on jugular venous saturation and it emphasizes that
      cerebral ischemia can be easily missed if no information on cerebral blood flow
      or regional metabolism is available.

PMID- 18639133
TI  - Failed stereotactic radiosurgery for acoustic neuroma.
AB  - A case of recurrent acoustic neuroma in a 58-year-old man is presented. The
      tumour was initially subtotally removed and then was irradiated using
      stereotactic radiosurgery. He represented with ataxia and new onset headache four
      years later and underwent further surgery for recurrence of his acoustic neuroma.
      The literature is reviewed and the authors' view point on the different
      modalities of treatment is discussed.

PMID- 18639134
TI  - Cerebellar haemangioblastoma and invasive macroprolactinoma: case report.
AB  - The case of a 42-year-old man harbouring both a symptomatic cerebellar
      haemangioblastoma and a huge, prolactin secreting invasive macroadenoma of the
      pituitary is presented. The possible pathogenesis is discussed and the literature
      reviewed with special emphasis on molecular genetic aspects.

PMID- 18639135
TI  - Virus-like particles in the aquatic fungus, Rhizidiomyces.
AB  - Isometric virus-like particles (VLPs), 60 nm in diameter, have been observed by
      electron microscopy in eight isolates of thermal-shocked Rhizidiomyces, a
      zoosporic, unicellular member of the Hyphochytridiales. VLP pathogenesis was
      observed in all fungal developmental stages from the zoospores to the mature
      sporangia. Paracrystalline structures associated with mitochondria preceded VLP
      occurrence in multinucleate sporangia. Particles appeared first in the intact
      nucleus, and subsequently VLPs completely replaced the nucleus and cytoplasm of
      the fungal host. Cell wall breakdown followed with release of VLPs into the
      medium. Approximately 50% of each fungal isolate was destroyed by the VLPs under
      stress conditions of heat, low nutrition, or aging. However, sufficient numbers
      of zoospores were capable of maturing into sporangia which produced zoospores to
      maintain the isolates in culture. After cloning 10 generations of zoospores, VLPs
      could still be produced in the offspring, thus indicating vertical transmission
      of the VLPs from generation to generation.

PMID- 18639136
TI  - Isolation and characterization of a double-stranded DNA mycovirus infecting the
      aquatic fungus, Rhizidiomyces.
AB  - Isometric particles 60 nm in diameter were isolated from the culture filtrate of
      the aquatic fungus, Rhizidiomyces, via pressure dialysis. The virus particles had
      a sedimentation coefficient of 625 S and a buoyant density of CsCI of 1.314 g/ml.
      The nucleic acid was dsDNA present as a single molecule (MW = 16.8 x 10(6)). Gel
      electrophoresis revealed 14+ protein bands ranging from MW of 84,500 to 26,000,
      with the largest one being dominant. This mycovirus appears to be distinct from
      all previously characterized viruses.

PMID- 18639137
TI  - Comparative serology of viruses isolated from ichneumonid parasitoids.
AB  - Serological relationships among viruses isolated from the ovaries of some
      ichneumonid wasps have been examined by immunoblotting. An antiserum prepared
      against purified Hyposoter exiguae virus reacted with polypeptides of calyx
      fluids isolated from species belonging to several different ichneumonid genera.
      Significant cross-reactions, however, were confined to three genera and usually
      involved only two to four polypeptides.

PMID- 18639138
TI  - A semipermissive nuclear polyhedrosis virus infection: characterization of
      infection kinetics and morphogenesis.
AB  - An in vitro host-range model system, designated System II, was developed for the
      multicapsid nuclear polyhedrosis virus Spodoptera frugiperda (SF-MNPV). This
      system consisted of SF-MNPV-infected S. frugiperda cells (permissive system) and
      SF-MNPV-infected Trichoplusia ni cells (semipermissive system). Infection kinetic
      studies revealed that while progeny virus was produced in the semipermissive
      system, the infectious virus yield was at least 700-fold lower than that in
      positive controls. Electron microscopy showed that the vast majority of progeny
      nucleocapsids in semipermissive infections were not enveloped and were found in
      only 5% of infected T. ni cells; the remaining 95% of the cells exhibited
      cytopathic effect as well as virogenic stroma. The data suggest that the
      infection in System II is restricted at or prior to the early stages of virion
      morphogenesis.

PMID- 18639139
TI  - Comparative sequence and structure of different isolates of citrus exocortis
      viroid.
AB  - The nucleotide sequences of two new Australian isolates of citrus exocortis
      viroid (CEV), CEV-DE25 and CEV-DE26, have been determined and compared with the
      previously sequenced Australian isolate, CEV-A (J. E. Visvader, A. R. Gould, G.
      E. Breuning, and R. H. Symons. FEBS Lett.137, 288-292 (1982).) and a Californian
      isolate, CEV-C (H. J. Gross, G. Krupp, H. Domdey, M. Raba, P. Jank, C. Lossow, H.
      Alberty, K. Ramm, and H. L. Sanger. Eur. J. Biochem.121, 249-257 (1982).).
      Sequencing of recombinant DNA clones prepared from purified CEV-A showed sequence
      heterogeneity at four nucleotide residues which was not observed by direct RNA
      sequencing. The data indicated that purified CEV-A contained minor amounts of at
      least one other CEV species designated CEV-AM. All isolates contain 371 residues.
      In comparison with the sequence of CEV-A, four residues are different in CEV-C
      and CEV-DE25 while CEV-DE26 has 27 nucleotide differences which include
      exchanges, insertions, and deletions. Most of the nucleotide differences in CEV
      C, CEV-DE25, and CEV-DE26 alter the proposed secondary structure relative to CEV
      A. No nucleotide differences were found to occur in the highly conserved central
      region previously shown to be present in the predicted native structures of CEV,
      potato spindle tuber viroid, chrysanthemum stunt viroid, and coconut cadang
      cadang viroid.

PMID- 18639140
TI  - Central pontine myelinolysis.
AB  - Central pontine myelinolysis (CPM) was initially associated with alcoholism.
      Subsequently other factors, including rapid reversal of hyponatraemia and extreme
      serum hypoosmolality associated with severe burns, have been identified as other
      important factors in its pathogenesis. Extra-pontine lesions have also been
      described. CPM may be found at autopsy, either having been overlooked during life
      or as an incidental finding. Its precise incidence is not known but the ability
      to diagnose it during life has been helped by modern neuroimaging, particularly
      magnetic resonance imaging (MRI) of the brain stem. In the past the prognosis for
      CPM was thought to be invariably fatal. It is clear now that with the greater
      general awareness of the disorder and the ability to diagnose it during life that
      some degree of recovery is possible. However, the number who do recover and the
      degree of recovery is not known. We report a 40-year-old man who developed CPM
      presenting with quadriparesis and inability to speak and swallow. There were risk
      factors for CPM and the diagnosis was confirmed by MRI scanning. He made a
      complete recovery although he remains ataxic. We are reporting this case as we
      believe it is important to make clinicians aware of the potential for recovery of
      CPM. While no specific treatment has been shown to influence the degree and rate
      of recovery of the demyelination, the fact that the quadriplegia and bulbar
      paralysis can recover fully is of considerable importance. In particular, it
      means that when the diagnosis is made, complete and vigorous nursing and medical
      care is warranted.

PMID- 18639141
TI  - Intraventricular recombinant tissue plasminogen activator for treatment of
      spontaneous intraventricular haemorrhage in pregnancy.
AB  - Spontaneous intracranial haemorrhage during pregnancy, which is usually
      subarachnoid or intraparenchymal in nature, causes significant maternal and
      foetal morbidity and mortality. Solitary intraventricular haemorrhage (IVH) in
      pregnancy has never been previously reported nor has the use of intraventricular
      fibrinolysis in this situation. A 28-year-old woman presented at 20 weeks'
      gestation with status epilepticus from spontaneous severe IVH. Angiography and
      magnetic resonance imaging did not show the presence of a vascular lesion or
      aneurysm. Thrombolytic treatment with intraventricular injection of recombinant
      tissue plasminogen activator (rt-PA) was instituted. Although the foetus aborted
      spontaneously 6 weeks after the haemorrhage and a ventriculo-peritoneal shunt for
      hydrocephalus was eventually required, the mother recovered to the level of mild
      disability at 3 months. Intraventricular fibrinolysis with rt-PA seems to be an
      effective form of treatment for IVH in pregnancy.

PMID- 18639142
TI  - Carotid artery reconstruction with a synthetic graft for aortitis syndrome.
AB  - We performed a carotid artery reconstruction with a double velour knitted Dacron
      graft in a 33-year-old Japanese woman with a left common carotid artery aneurysm
      caused by the aortitis syndrome. After inflammatory signs resolved on steroid
      administration, a carotid artery reconstruction was performed. One month after
      the operation, the internal carotid artery was narrowed at the distal anastomosis
      site and 10 months later the same site showed aneurysmal dilatation. We conclude
      that it is important to control inflammation for a prolonged period and perform
      angiography regularly after such an operation.

PMID- 18639143
TI  - Serial MR and CT features of primary germinoma originating in the basal ganglia.
AB  - Serial changes of neuroradiological findings in a 10-year-old boy with primary
      germinoma originating in the basal ganglia are reported. He presented with a one
      year history of slowly progressive right hemiparesis. Although initial computed
      tomography (CT) scans showed no prominent abnormalities, a slight high-density
      area in the basal ganglia became conspicuous with cortical atrophy on follow-up
      scans. Sequential magnetic resonance images showed a homogeneous lesion with
      clear margin and remarkable postcontrast enhancement. Two cell pattern germinoma
      was histologically verified by CT guided stereotactic biopsy. Following
      irradiation, the tumour completely disappeared, however, the atrophy of the
      cerebral hemisphere and the brain stem progressed, and mild hemiparesis remained.
      We discuss the neuroradiological features and clinical manifestations of this
      disease.

PMID- 18639144
TI  - Nitrous oxide-induced vitamin B(12) deficiency.
AB  - Two patients with asymptomatic vitamin B(12) deficiency developed a peripheral
      neuropathy 6-7 weeks after exposure to nitrous oxide during general anaesthesia,
      and 3 and 11 days after receiving cyclophosphamide. The serum B(12) concentration
      was less than 20 pmol/l and the symptoms resolved after B(12) replacement. We
      believe that the neurological symptoms were triggered by exposure to nitrous
      oxide. A possible novel feature in these patients was the close temporal
      relationship between the onset of the symptoms and cyclophosphamide treatment. It
      is possible that cyclophosphamide reduced the availability of remaining B(12)
      stores.

PMID- 18639145
TI  - Cervical root injury caused by vertebral artery dissection.
AB  - Vertebral artery dissection is a common cause of posterior circulation strokes in
      young and middle-aged adults. Peripheral motor deficits have been rarely
      described in association with vertebral artery dissection. Peripheral motor
      involvement may be due to compression of the spinal nerves by an enlarged
      vertebral artery. It may also result from ischaemia of the anterior horn or the
      spinal nerves by occlusion of a spinal radicular artery that originates from the
      vertebral artery. Magnetic resonance imaging (MRf) and magnetic resonance
      angiography (MRA) offer the possibility of easy, non-invasive diagnosis of a
      vertebral artery dissection. Acute treatment with anticoagulants is warranted to
      prevent the progression of neurologic deficits due to intraluminal thrombus or
      artery to artery emboli. This case report describes a patient in whom vertebral
      artery dissection was associated with an unusual presentation with a peripheral
      motor deficit in the upper limb and recurrent central ischaemic neurological
      events.

PMID- 18639146
TI  - A case of thyrotoxicosis with chorea: association with anti-phospholipid
      antibody.
AB  - We report a case of thyrotoxicosis associated with chorea and detectable anti
      phospholipid antibodies in which a structural abnormality could not be detected
      on routine imaging but cerebral perfusion single photon emission computed
      tomography scans suggested a reversible alteration of basal ganglia perfusion.
      The pathophysiological mechanisms of phospholipid antibody causing chorea in
      thyrotoxicosis are discussed.

PMID- 18639147
TI  - Treatment of an intracranial germinoma spinal metastasis.
AB  - A 20-year-old male with a solitary intradural extramedullary spinal metastasis
      from a pineal germinoma presented with progressive spinal cord compression. This
      was initially treated with radiotherapy and the patient showed rapid clinical
      improvement with complete resolution of his neurological symptoms and signs.
      Subsequent systemic chemotherapy resulted in complete radiological resolution of
      the lesion. This case is presented to demonstrate radiotherapy and chemotherapy
      as a treatment option for germinoma 'drop' metastasis causing spinal cord
      compression, along with a review of the literature.

PMID- 18639148
TI  - Spontaneous pneumocephalus.
AB  - Pneumocephalus (PC) is defined as an intracranial gas collection. The majority of
      cases of PC are secondary to trauma or are iatrogenic. Spontaneous, non-traumatic
      PC is an uncommon condition. Most cases of spontaneous PC occur in association
      with infection, neoplasia or disease of otogenic origin. The case of spontaneous
      PC being presented was felt to have resulted from air being forced into a small
      deficit in the posterior wall of the sphenoid sinus following an episode of nose
      blowing.

PMID- 18639149
TI  - Rupture of a giant middle cerebral aneurysm after blunt head injury.
AB  - A 20-year-old man was involved in a fight while under the influence of alcohol.
      He subsequently developed an intracerebral haemorrhage in the putamen with a
      minimal subarachnoid haemorrhage and died. An autopsy revealed a ruptured giant
      saccular aneurysm of the middle cerebral artery. We believe that the blunt head
      injury caused a rupture of the pre-existing giant saccular aneurysm either
      through the force transmitted from the blow, or by a possible transient elevation
      of the blood pressure secondary to the excitement of the fight, or by a
      combination of both factors.

PMID- 18639150
TI  - Neurological society of australasia, annual scientific meeting, 17-19 September
      1998.

PMID- 18639151
TI  - Evidence for pH-induced release of RNA from belladonna mottle virus and the
      stabilizing effect of polyamines and cations.
AB  - The RNA of belladonna mottle virus (BDMV) is released from virions by increasing
      the pH to neutrality or above, leaving behind intact protein shells. In contrast,
      much harsher conditions are required to release the RNA from the closely related
      turnip yellow mosaic virus (TYMV). The heat-induced or pH-dependent escape of RNA
      from BDMV has been investigated by 31P NMR spectroscopy and ultracentrifugation.
      The methods show a transition pH near 6.8 at which the RNA undergoes a structural
      alteration probably caused by disruption of protein-RNA linkages. Addition of
      cations or polyamines to BDMV prevents the RNA loss at alkaline pH; the virions
      become stable to pH values up to 11.5 as observed for TYMV. We suggest that
      repulsion of the negatively charged phosphate groups of the nucleic acid provides
      the driving force for RNA release at pH values above the threshold point where
      protein-RNA interactions are broken. The polyamines effectively counter the
      phosphate charge in BDMV and thereby prevent RNA loss. Since TYMV is packaged
      with polyamines and BDMV is not (R. Virudachalam, K. Sitaraman, K. L. Heuss, P.
      Argos, and J. L. Markley, Virology 130, 360-371, 1983), the different conditions
      required for RNA escape from the two viruses are explained. Heating of BDMV
      virions at pH 7.0 to 40 degrees resulted in their partial disruption; the product
      some intact particles, empty capsids, and RNA fragments with a sedimentation
      coefficient of 5S.

PMID- 18639152
TI  - Carbon-13 and proton nuclear magnetic resonance spectroscopy of plant viruses:
      evidence for protein-nucleic acid interactions in belladonna mottle virus and
      detection of polyamines in turnip yellow mosaic virus.
AB  - Belladonna mottle virus (BDMV) enriched in carbon-13 was isolated from infected
      tobacco plants grown in a 2% 13C02, 8% 12CO2 atmosphere. The enrichment led to a
      fivefold improvement in the signal to noise ratio of the (13)C NMR spectrum of
      BDMV. 1H and 13C NMR peaks of the intact virion are broad. However, upon removal
      of the RNA, many sharp peaks appear in spectra of the empty capsid which are
      attributed to aliphatic amino acid side chains at the inner surface of the
      protein shell that have gained segmental mobility. These include resonances
      assigned to the side chain of glutamate. Internal motions are necessary to
      account for the experimental 13C NMR linewidths. Aliphatic 13CHn (n = 1-3) groups
      must have correlation times on the order of 10 nsec and quaternary carbons must
      have correlation times between 50 and 300 nsec to explain the narrow line widths.
      No sharp peaks were observed in the aromatic regions of 1H or 13C NMR spectra;
      thus all the aromatic side chains seem to be tightly packed in the capsid as well
      as the virion. 1H and 13C NMR have been used for the first time to detect
      polyamines in virus particles. 1H NMR studies confirmed the presence of
      polyamines, apparently packaged during assembly, in turnip yellow mosaic virus
      (TYMV) and demonstrated their absence in BDMV. Sedimentation analysis has shown
      that the RNA is released upon increasing the pH above neutrality for BDMV but
      only above pH 11.5 for TYMV (R. Virudachalam, K. Sitaraman, K. L. Heuss, J. L.
      Markley, and P. Argos, Virology 130, 351-359, 1983). 1H NMR studies demonstrated
      that the BDMV capsid is permeable to polyamines and that the pH stability of BDMV
      with added spermidine is comparable to that of TYMV.

PMID- 18639153
TI  - Comparison of sequence diversity in several cytoplasmic polyhedrosis viruses.
AB  - Sequence homology among several different cytoplasmic polyhedrosis virus (CPV)
      types and the human reovirus (type 1) was examined by Northern blot analysis and
      S, nuclease analysis, using random-primed cDNA probes synthesized from total
      genomic RNA. The results show no homology among the CPV type 1, Bombyx mori CPV,
      type 5, Orgyia pseudotsugata CPV, type 8, Manduca sexta CPV and the human
      reovirus (type 1). However, there was significant homology among three type 5
      CPVs, O. pseudotsugata CPV, Euxoa scandens CPV, and Heliothis armigera CPV. The
      O. pseudotsugata CPV and E. scandens CPV were 43-44% homologous while each was 6
      13% homologous with the H. armigera CPVusing stringent conditions of
      hybridization.

PMID- 18639154
TI  - Complexity of the Argentina mild strain of barley stripe mosaic virus.
AB  - Barley stripe mosaic virus (BSMV) is known to have unusual strain-specific
      variations in the number of high molecular weight RNAs that can be resolved by
      gel electrophoresis. Analysis with recombinant DNA clones has revealed that all
      strains contain three distinct hybridizing species of RNA, which we now designate
      alpha, beta and y. The alpha- and beta-RNAs are about 4200 and 3650 nucleotides
      (NT), respectively, but the gamma-RNAs vary in size depending on the strain. The
      gamma-RNA of the Type strain is 3650 NT, and is difficult to resolve from beta
      RNA by gel electrophoresis. However, the gamma-RNA of the North Dakota 18 (ND18)
      strain is 3250 NT and is clearly separated from beta-RNA. The results presented
      below show that the Argentina mild (AM) strain contains a mixture of gamma-RNAs
      of 3650, 3250, and 2900 NT. The 3650- and 3250-NT gamma-RNAs appear to be
      functional because AM subclones containing either 3650- or 3250-NT gamma-RNA can
      be isolated from plants inoculated with low concentrations of virus. The 2900-NT
      gamma-RNA is probably not capable of functioning as a genomic RNA because this
      RNA is not a component of any of the AM subclones.

PMID- 18639155
TI  - The synthesis and processing of the nepovirus grapevine fanleaf virus proteins in
      rabbit reticulocyte lysate.
AB  - Translation of a mixture of the two grapevine fanleaf virus (GFLV) RNAS in
      reticulocyte lysates in the presence of the amino acid analogs canavanine, S
      aminoethyl-cysteine, and p-fluorophenylalanine gave two products of molecular
      weights (Mr) 220,000 (from RNA-1) and 125,000 (from RNA-2). In the absence of
      these analogs a protease apparently induced by RNA-1 catalyzed cleavage of the
      RNA-2 product (Mr 125,000) into two proteins of Mr 68,000 and 58,000. The 58,000
      Mr protein was shown to be the likely virus coat protein by peptide mapping after
      partial proteolysis. Cleavage of the RNA-2 product of GFLV was not catalyzed by
      the translation products of another nepovirus, tobacco ringspot virus.

PMID- 18639156
TI  - Modulation of light delivery in photodynamic therapy of brain tumours.
AB  - This study was performed to determine whether modulation of light delivery could
      improve tumour kill in photodynamic therapy (PDT) of brain tumours, as optimal
      dosimetry has not been fully established. One hundred and sixty-five adult Wistar
      rats were treated, of which 70 had an implanted C6 cerebral glioma.
      Haematoporphyrin derivative (HpD) was injected at doses between 0 and 20 mg/kg,
      24 h prior to irradiation with 630 nm laser light. The total energy dose was
      varied from 0 to 1200 J/cm(2), with fluence rates of 625, 3125 or 9375 mW/cm(2).
      In some studies, the light delivered at 3125 mW/cm(2) was divided into 10
      fractions of approximately 13 s, with refractory intervals of 60 s. The most
      striking finding was that HpD was much more potent than previously reported. All
      doses greater than 1.0 mg/kg resulted in normal brain damage with light doses
      above 50 J/cm(2). However, at 1.0 mg/kg, significant normal injury was not
      apparent until 1200 J/cm(2). Failure of drug-light dose reciprocity indicated
      that photobleaching occurred, protecting normal tissue. Selective tumour kill was
      observed to 2.2. mm depth (SE +/- 0.44 mm). Using lower power or fractionated
      light did not improve tumour kill and normal tissue injury occured with fluence
      rates of 9375 mW/cm(2). In conclusion, the doses of HpD currently used in
      clinical brain tumour trials may be too high to achieve selective tumour kill.
      Higher light fluence rates allowed shorter intraoperative irradiation times with
      no loss of efficacy. Photodynamic therapy continues to demonstrate potential as
      an effective treatment for local control of cerebral lesions.

PMID- 18639157
TI  - Sequential changes and recoveries of the motor evoked potential in experimental
      hypertension.
AB  - The D- and I-waves of the motor evoked potential (MEP) were investigated as a
      monitor for acute intracranial hypertension in 20 dogs. Intracranial pressure
      (ICP) was raised bvy inflation of an extradural balloon. The MEP elicited by
      electrical transcortical stimulation were recorded during inflation and deflation
      of the balloon. The D-waves were linearly suppressed according to the ICP level,
      however, the I-waves and the ICP level did not correlate. Each wave disappeared
      in the animals kept about 50 mmHg or more, whose pupils were dilated. In the
      animals kept under 60 mmHg, the amplitude of the D-wave recovered proportionate
      to the period during which the amplitude was suppressed less than 50%. The
      changes of the MEP have some relation to histopathological changes. The results
      demonstrate that the D-wave of MEP is a useful monitor for intracranial
      hypertension.

PMID- 18639158
TI  - Repair under cardiopulmonary bypass of giant internal carotid aneurysm following
      GDC embolization.
AB  - Endovascular embolization techniques have increased the complexity of aneurysm
      surgery in those lesions that have been incompletely obliterated. We report a
      case of giant cerebral aneurysm initially treated with Guglielmi detachable coils
      which required cardiopulmonary bypass for successful endoaneurysmorrhaphy.

PMID- 18639159
TI  - Treatment of giant cystic craniopharyngiomas.
AB  - We report two patients with giant cystic craniopharyngiomas approached
      transsphenoidally, with continuous cyst drainage through a silastic tube,
      connecting the cyst with the sphenoid sinus. An innovative technique for fixation
      of the tube and reconstruction of the sphenoid sinus is presented which consists
      of the use of a combination of silk, resin and calcium carbonate.
      Postoperatively, although both patients developed diabetes insipidus, both
      patients improved neurologically. At follow-up examinations (32 and 48 months),
      neither patient had migration of the silastic tube, evidence of meningitis, nor
      cerebrospinal fluid leak. We propose this technique as a surgical alternative for
      large cystic craniopharyngiomas on which attempt of total resection carries a
      high risk of severe neurological complications.

PMID- 18639160
TI  - Acute haemorrhagic presentation of an intracranial meningioma.
AB  - Acute haemorrhagic presentation of a meningioma is an extremely rare event. In a
      review of the literature, 44 such cases were found and only eight of them
      presented with sudden onset of coma. The outcome in these eight cases was, with
      few exceptions, poor. We report the case of a 72-year-old woman who presented
      with sudden onset of coma due to a massive haemorrhage into a frontal meningioma.
      The diagnosis was suspected on the basis of a non-enhanced computed tomographic
      (CT) scan and considering the clinical status of the patient, emergency
      evacuation of the haematoma and complete macroscopic resection of the tumour was
      performed without further diagnostic procedures. The patient fully recovered.
      Clinical examination and contrast enhanced CT scan at 3 months follow-up were
      considered normal. The prognosis for haemorrhagic presenting meningiomas is poor
      especially for those presenting with acute onset of coma. The outcome seems to be
      improved with rapid decompression and tumour removal. We would like to stress the
      need to keep the diagnostic procedures to a minimum once a haemorrhagic
      decompensating meningioma is suspected despite the risks associated with an
      incomplete radiological work up before surgery. Complete or at least gross tumour
      removal at the time of emergency surgery seems to be associated with a better
      outcome and should be attempted in all patients, even those presenting with acute
      signs of herniation.

PMID- 18639161
TI  - Extradural vertebral artery dissecting aneurysm causing subarachnoid haemorrhage.
AB  - The authors report the case of a 37-year-old man who presented with subarachnoid
      haemorrhage (SAH) after rupture of an extradural vertebral artery dissecting
      aneurysm. The patient underwent a left lateral suboccipital craniotomy with
      removal of the medial part of the occipital condyle and the fusiform dilatation
      was coated. The angiograms 3 months after surgery showed aneurysm resolution and
      normal vessel calibre. To the authors' knowledge, it is the second reported case
      of extracranial vertebral aneurysm of its kind presenting as SAH. The result
      after surgery in this case indicates that coating of a dissecting aneurysm of the
      extracranial portion of the vertebral artery (VA) is a valid alternative surgical
      technique for the prevention of rebleeding.

PMID- 18639162
TI  - Relapse and subarachnoid dissemination of a pineal germinoma 14 years after
      radiation therapy.
AB  - Intracranial germinomas are rare tumours which are highly curable with
      radiotherapy. In recent years treatment with chemotherapy has gained importance.
      Recurrence and dissemination is seen in about 10-20% of cases within the first 2
      years after diagnosis; late recurrence and dissemination is very rare. We
      describe a patient with a recurrent germinoma 14 years after radiotherapy of a
      pineal tumour. We further report the management with chemotherapy, the late side
      effects of radiotherapy and the course of the disease with its fatal
      dissemination. We conclude that the use of radiotherapy, despite being highly
      effective, is clearly limited by its late side-effects. New regimens with
      chemotherapy seem promising but proved to be less effective in our case with
      tumour seeding throughout the subarachnoid space.

PMID- 18639163
TI  - Teratoma of the conus medullaris.
AB  - Intramedullary teratoma is a rare neoplasm. To our knowledge only 10 cases have
      been reported so far, eight of mature teratoma and two of immature. We present a
      new case of mature teratoma located in the conus medullaris. After 2 years
      increasing complaints and worsening neurologic deficits, the neoplasm was
      discovered by magnetic resonance imaging and was completely resected surgically.
      Similar cases are reviewed and the clinical, radiological, surgical and
      morphological aspects of this lesion will be discussed. In the majority of cases,
      the tumour has an indolent growth rate and recovery after resection is good.

PMID- 18639164
TI  - Infra-optic course of the anterior cerebral artery.
AB  - This report describes the infra-optic course of an anterior cerebral artery in a
      67-year-old man. An aneurysm was also incidentally detected at the anterior
      communicating artery. Thirty-three cases have been published previously and the
      literature concerning this anomaly is reviewed.

PMID- 18639165
TI  - Idiopathic granulomatous myositis: does the clinical spectrum include polymyalgia
      rheumatica?
AB  - Granulomatous inflammation restricted to muscle is an uncommon cause of myopathic
      syndromes. Two patients were diagnosed with idiopathic granulomatous polymyositis
      after appropriate investigations failed to reveal a systemic or alternative
      explanation for the granulomas seen in their muscle biopsy. One patient presented
      with a syndrome indistinguishable from polymyalgia rheumatica but both patients
      manifested disabling myalgias which were strikingly corticosteroid responsive.
      The two cases underscore the potential importance of muscle biopsy in polymyalgic
      states, the non-specificity of polymyalgia rheumatica as a syndrome which can be
      simulated by other disorders including granulomatous myositis, and the potential
      corticosteroid responsiveness of prominent, functionally limiting myalgias which
      can be seen in this disorder. Some controversy continues regarding the correct
      nosology of this disease, largely perpetuated by an awareness of the inherent
      limitations of current non-invasive evaluation techniques to confirm occult
      granulomatous involvement of non-myogenous organs.

PMID- 18639166
TI  - Neurosarcoidosis presenting as an isolated mass of the quadrigeminal plate.
AB  - A rare case of neurosarcoidosis presenting as an isolated quadrigeminal plate
      mass without systemic manifestation of this disease is reported. This 26-year-old
      man presented with symptoms of acute intracranial hypertension including
      headache, morning vomiting as well as a right homonymous hemianopsia. Magnetic
      resonance imaging (MRI) showed an expansive tectal mass causing hydrocephalus
      secondary to an aqueductal obstruction. An external ventricular drainage was
      inserted and the mass, postulated to be a glioma, was removed through an
      occipital transtentorial craniotomy. Histopathological examination revealed
      numerous sarcoid granulomas. Postoperative course was relevant for bilateral
      hypoacusis and tinnitus, blurred vision, bilateral palpebral ptosis and bilateral
      internuclear ophthalmoplegia. Chest X-ray was normal. Postoperative thoracic
      computed tomography (CT) scan showed mediastinal adenopathies. Lung function
      tests were normal. Angiotensin converting enzyme (ACE) cerebrospinal fluid (CSF)
      blood ratio was normal. Postoperative treatment and follow-up included
      corticosteroids, serial lung function tests and cerebral MRI. Neurosarcoidosis
      may present with protean clinical manifestations and unusual radiological
      features. This rare diagnosis has to be kept in mind when facing isolated
      intracerebral mass lesions.

PMID- 18639167
TI  - Zoster related multiple cranial nerve palsies: an unusual complication following
      percutaneous balloon compression for trigeminal neuralgia.
AB  - A patient demonstrating multiple cranial nerve palsies involving the IXth, Xth,
      XIth and XIIth cranial nerves following percutaneous balloon compression of the
      trigeminal ganglion for post-herpetic trigeminal neuralgia is presented. This
      collection of lower cranial nerve palsies, including the accessory nerve, has not
      been previously described as a complication of this procedure. This unusual group
      of cranial nerve palsies resulted from reactivation of the varicella-zoster virus
      (VZV) secondary to the procedure.

PMID- 18639168
TI  - Imaging appearances of meningeal melanocytoma.
AB  - Meningeal melanocytoma is an uncommon, benign melanocytic tumour of the meninges.
      Only 15 cases have been reported to date. We present the MR and CT appearance of
      a case of compressive myelopathy due to cervical meningeal melanocytoma. Careful
      analysis of the imaging features, as illustrated in the present case, allows a
      preoperative diagnosis. The differential diagnosis includes malignant melanoma
      and melanocytic meningioma.

PMID- 18639169
TI  - Traumatic carotid artery occlusion following blunt cervical injury.
AB  - Two cases of overlooked, traumatic unilateral occlusion of the carotid artery are
      reported. Postmortem revealed occlusion of the internal carotid artery in one
      case and that of the common carotid artery in another. The progression of the
      morbid state, along with the management with emphasis on the significance of the
      carotid angiogram and follow-up repeated computed tomography are mentioned.
      Although traumatic occlusion of the common carotid artery is not as common as
      that of the internal carotid artery, both entities are well known to produce
      morbidity and mortality.

PMID- 18639170
TI  - Moyamoya disease associated with basilar tip aneurysm.
AB  - Direct surgical intervention to treat ruptured basilar tip aneurysms in patients
      with moyamoya disease has rarely been attempted, and patients who have undergone
      such treatment have not fully recovered. We review six cases of surgically
      treated ruptured basilar tip aneurysm associated with moyamoya disease, including
      our own case to illustrate aspects of surgical intervention and the difficulties
      encountered. Patients who underwent surgery after 4 weeks of the onset of
      symptoms showed impressive results. Of the patients who underwent surgery in the
      acute stage, two died, including our patient, and one showed excellent recovery.
      It is emphasized that to achieve satisfactory surgical outcome, the following
      factors should be considered: (i) delayed operation is preferable, with
      extracranial-intracranial bypass in selected patients; (ii) careful preservation
      of moyamoyas and transdural collaterals is mandatory; (iii) intraoperative
      rupture of the aneurysm should be avoided; and (iv) using a neuroanaesthetic
      technique of induced hypothermia and hypertension may be preferable.

PMID- 18639172
TI  - Size and complexity of polyadenylated RNAs induced in tobacco infected with
      sonchus yellow net virus.
AB  - Hybridization of 32P-labeled sonchus yellow net virus (SYNV) RNA to
      polyadenylated (poly A+) RNA from infected tobacco reveals the presence of four
      electrophoretically distinct components. These components probably represent five
      discrete RNA species complementary to SYNV RNA (scRNAs). The scRNAs are smaller
      than the 13,000 nucleotide (NT) SYNV genome and range in size from 1200 to 6600
      NT. Individual recombinant DNA clones derived from SYNV RNA hybridize to at least
      three and probably four of the scRNAs. These results suggest that each of the
      scRNAs contains unique sequences with a combined size representing more than 90%
      of the viral genome. Therefore, the size range and sequence complexity of the
      scRNAs are as expected for messenger RNAs encoding the four major SYNV
      polypeptides and the minor "L-protein."

PMID- 18639173
TI  - A study of the glycoproteins of Autographa californica nuclear polyhedrosis virus
      (AcNPV).
AB  - Pulse labeling with tritiated mannose was used to follow the time course of
      Autographa californica nuclear polyhedrosis virus (AcNPV) glycoprotein synthesis
      in Spodoptera frugiperda IPLB-21 cells. Nine viral-induced intracellular
      glycoproteins were first detected from as early as 2 hr postinoculation (67K,
      early phase) to as late as 14 hr (36K and 19K glycoproteins, intermediate phase).
      Glycosylation of these proteins was observed to continue to the end of the
      experiment (28 hr postinoculation). Seven of these intracellular glycoproteins
      could also be detected in infected Trichoplusia ni TN-368 cells 24 hr
      postinoculation. When the glycosylation inhibitor tunicamycin was present (from 0
      hr postinoculation) there was no detectable glycosylation of any of these viral
      induced glycoproteins. Metabolic labeling of the nonoccluded virus budded from
      IPLB-21 and TN-368 with tritiated mannose or N-acetylglucosamine identified 11
      structural glycoproteins, 8 of which were identical in both virus preparations.
      All of these structural glycoproteins were sensitive to the inhibitory action of
      tunicamycin. A single 42K structural glycoprotein was detected (with
      acetylglucosamine only) in the occluded form of AcNPV. Glycosylation of this
      structural protein appeared to be insensitive to tunicamycin. Lactoperoxidase
      catalyzed radioiodination was used to determine which of the virus structural
      glycoproteins are exposed on the virion surface.

PMID- 18639174
TI  - Virus protein synthesis in alfalfa mosaic virus infected alfalfa protoplasts.
AB  - Four proteins unique to virus infection were synthesized in alfalfa mosaic virus
      infected alfalfa mesophyll protoplasts. These proteins, P1, P2, P3, and coat
      protein comigrated on electrophoresis with the major in vitro translation
      products of RNA 1, RNA 2, RNA 3, and RNA 4, respectively. P1, P3, and coat
      protein were observed at 5 hr post inoculation; P2 was detected at 9 hr post
      inoculation. The three nonstructural proteins accumulated most rapidly early in
      infection until about 15 hr post inoculation; stable protein levels were
      maintained thereafter. Coat protein accumulated rapidly until about 20 hr after
      inoculation. All four virus RNA species were detected in infected protoplasts by
      labelling with [3H]uridine. Ultraviolet irradiation of protoplasts prior to
      inoculation was necessary for virus protein detection, but it severely depressed
      the synthesis of RNA 1 and RNA 2 relative to RNA 3 and RNA 4.

PMID- 18639175
TI  - Analysis of viral RNA isolated from tobacco leaf tissue infected with tobacco
      etch virus.
AB  - Total RNA has been isolated from tobacco seedlings systemically infected with the
      potyvirus, tobacco etch virus (TEV). Analysis of this RNA by agarose gel
      electrophoresis under denaturing conditions, in conjunction with gel
      hybridization using various virus-specific nucleic acid probes, revealed genomic
      length TEV RNA and eight zones of less-than-full-length RNA. However,
      reconstitution experiments demonstrated that the zones were electrophoretic
      artifacts and not authentic subgenomic RNAs. Furthermore, only a single
      polyadenylated viral RNA species, which comigrated with TEV genomic RNA in gel
      electrophoresis studies, was isolated from infected tobacco leaf tissue.
      Translation of polyadenylated RNA in a rabbit reticulocyte lysate resulted in the
      synthesis of four high-molecular-weight virus-specific products. The products had
      apparent molecular weights and serological reactivities as follows: (1) 120,000,
      reaction with antiserum to TEV cytoplasmic inclusion protein; (2) 87,000, no
      serological reaction detected; (3) 85,000, reaction with antisera to TEV capsid
      protein and the large-molecular-weight component of the nuclear inclusion body;
      (4) 49,000, reaction with antiserum to the small-molecular-weight component of
      the nuclear inclusion body.

PMID- 18639176
TI  - Replication of tobacco mosaic virus. VII. Further characterization of single- and
      double-stranded virus-related RNAs from TMV-infected plants.
AB  - The single-stranded (ss) and double-stranded (ds) RNAs produced in tobacco tissue
      as a result of infection by tobacco mosaic virus (TMV) have been reinvestigated.
      32P-labeled probes consisting of either cDNA or viral RNA, complementary to
      specific regions of either the viral RNA or its negative strand, respectively,
      were used in "Northern" hybridization experiments. Of the 10 ssRNA bands
      observed, all but four appeared to be artifacts of electrophoresis. These four
      RNAs were found on polyribosomes and are presumed to be true mRNAs; three were
      identified as the well-known genomic RNA, the I2-mRNA and the coat protein mRNA,
      or LMC. The fourth RNA species of MW approximately 1.2 x 10(6) had not previously
      been specifically identified as a subgenomic RNA of TMV. The viral RNA which gave
      rise to the six artifactual ssRNA bands was heterogeneous in size and was shown
      to be encapsidated in vivo. Upon electrophoresis, these heterogeneous RNA
      fragments comigrated approximately with plant rRNAs also present in the extracts,
      generating the observed artifactual bands. Four dsRNAs were also identified. From
      molecular weight and hybridization analyses, they appeared to be double-stranded
      forms of the above four polyribosome-associated ssRNAs. Attempts to translate
      proteins from the denatured dsRNAs in vitro were unsuccessful. A population of
      low-molecular-weight, TMV-specific ssRNAs, (+) and (-) in sequence, was generated
      during infection; however these RNAs were believed to be breakdown products.

PMID- 18639178
TI  - Literature review.
AB  - This paper is a compilation and summary of the various published experiences of
      tension pneumocephalus. It aims to provide a comprehensive guide to the
      incidence, mechanism, clinical setting, symptoms, diagnosis, management,
      prevention and prognosis of this oftentimes unrecognized clinical scenario. This
      condition is of interest to neurosurgeons, otolaryngologists, anaethetists and
      radiologists alike.

PMID- 18639177
TI  - Nucleotide sequence of the polyhedrin gene of Autographa californica nuclear
      polyhedrosis virus.
AB  - The nucleotide sequence of a 1143-bp region of Autographa californica MNPV
      (AcMNPV) DNA containing the entire coding region of polyhedrin was determined.
      The coding region consisted of 732 bp without intervening sequences. The 5'
      leader sequence was approximately 58 nucleotides in length. A putative "TATA box"
      and "CAAT box" were located 20 and 52 bp upstream from the transcriptional start
      site, respectively. Two tandem repeats of 8 bp were found 70 and 84 bp upstream
      from the transcriptional start site. The molecular weight of polyhedrin, as
      deduced from the nucleotide sequence, was 28,872. The amino acid sequence of
      AcMNPV polyhedrin was very similar to the amino acid sequence of Bombyx mori
      polyhedrin.

PMID- 18639179
TI  - Australian association of neurologists, annual scientific meeting, 24-28 may
      1999.

PMID- 18639180
TI  - Brain tumour invasion: Many cooks can spoil the broth.

PMID- 18639181
TI  - Pressure gradients within the central nervous system.
AB  - The existence of clinically relevant pressure gradients within the central
      nervous system (CNS) is the subject of ongoing debate. Such gradients, if they do
      exist, would have significant implications for intracranial pressure (ICP)
      monitoring and ICP management in traumatic brain injury. As summarised in this
      short review, there is considerable experimental and clinical evidence that ICP
      is not evenly distributed within the central nervous system. Larger clinical
      trials on the implications of ICP gradients are warranted to address questions on
      the correct placement of ICP probes and on ICP management. It seems paradoxical
      to develop and employ ever more sophisticated monitoring devices in traumatic
      brain injury, such as monitoring of CNS metabolites with microdialysis or near
      infrared spectroscopy, while fundamental issues such as the existence of ICP
      gradients remain unresolved.

PMID- 18639182
TI  - Outcome and complications of reconstruction of the thoracolumbar spine for
      vertebral tumours.
AB  - Forty-six patients with progressive neurological deficits or severe pain
      underwent subtotal vertebrectomy and resection of thoracic and lumbar vertebral
      tumours. Following subtotal vertebrectomy, 22 spinal segments were reconstructed
      with titanium mesh cylinders, 13 with allograft struts, 7 with methyl
      methacrylate, one with autograft bone, and 2 patients underwent spinal
      reconstruction with miscellaneous materials. In one patient, 40 mm cancellous
      screws and a titanium mesh cylinder filled with methyl methacrylate were used.
      Following the reconstruction, 34 patients underwent stabilisation with anterior
      plates, and 5 patients with posterior rods and pedicle screws. No instrumental
      fixation was used in 7 patients. Postoperatively, 9 patients who had severe pain
      but no preoperative neurological deficits remained neurologically intact. Of 33
      patients with preoperative incomplete deficit (Frankel grades C and D), 14
      improved, 18 were unchanged, and one was worse. Of 3 patients in Frankel grade B,
      2 improved to grade C but did not recover ambulation and the third patient
      remained at Frankel grade B. Other complications included 2 perioperative deaths
      due to respiratory failure and coagulopathy, one postoperative deterioration, and
      optic neuropathy in one patient. Backed out screws were seen in 2 patients.
      Although spinal reconstruction and instrumentation systems allow for immediate
      stability and mobilisation, a significant perioperative morbidity warrants a
      careful patient selection.

PMID- 18639183
TI  - Lateral pallidotomy exacerbates akinesia in the Parkinsonian patient.
AB  - Despite the recent resurgence of interest in the use of pallidotomy for the
      treatment of Parkinson's disease, there remains considerable debate about the
      optimal lesion site. Although the current understanding of the neural mechanisms
      underlying Parkinsonism would suggest that the medial pallidum is the logical
      site for alleviation of symptoms, some surgeons still advocate lesions in the
      lateral pallidum. We report the case of such a lesion placement verified
      pathologically, which resulted in exacerbation of akinesia postoperatively. This
      demonstrates that accurate targeting in the pallidum is critical to avoid
      exacerbation of symptoms by lesioning the lateral pallidum.

PMID- 18639184
TI  - Magnetic stimulation in cervical radiculopathy and health controls.
AB  - Magnetic stimulation was performed in 15 cases of unilateral cervical
      radiculopathy and 16 age-matched healthy controls. Among the muscle potentials
      which have acute slope and high amplitude, the difference between the minimal and
      the maximal latency in the same muscle was defined as variability. In the healthy
      control group, the variability of the muscle potentials evoked by head magnetic
      stimulation was approximately 2 ms. In cervical radiculopathy, the muscle
      potential latencies in head magnetic stimulation were normal except for one case
      because of the wide normal range. However, the interside difference of the muscle
      potential latency in head magnetic stimulation was significantly greater in the
      cervical radiculopathy group than in the healthy control group. This suggests
      that the interside difference of the muscle potential latency is more sensitive
      than the muscle potential latency in head magnetic stimulation in unilateral
      radiculopathy.

PMID- 18639185
TI  - Dural sinus thrombosis: a mechanism-based classification and review of 42 cases.
AB  - Cranial venous outflow obstruction due to dural sinus thrombosis may result in
      venous hypertension, cerebral infarction, cerebral haemorrhage or impaired
      cerebrospinal fluid (CSF) absorption with consequent pseudotumour syndrome. We
      propose a mechanism based classification of dural sinus thrombosis from these
      four outcomes. Forty two cases of dural sinus thrombosis presenting to Royal
      Prince Alfred Hospital between 1986-1997 were retrospectively reviewed. These
      cases were classified according to mechanism of presentation and relevance of
      this to site of thrombosis, treatment and prognosis. This study shows that the
      superior sagittal sinus and transverse sinus are the commonest sites of
      thrombosis, and multiple sites of thrombosis (69%) are more frequent than a
      single site. Magnetic resonance imaging (MRI) with venous flow studies is the
      investigation of first choice for diagnosis but angiography remains the gold
      standard. A pseudotumour syndrome is the commonest presentation (43%) followed by
      cerebral haemorrhage (31%). The overall prognosis for sinus thrombosis is good,
      with 71% of cases recovering to normal function.

PMID- 18639186
TI  - Successful psychotropic management of drug related psychosis in Parkinson's
      disease.
AB  - This study reports on the clinical effectiveness of the combined use of
      conventional major tranquillisers and augmented levodopa dosage for the
      management of paranoia, hallucinations and confusion in patients with Parkinson's
      disease (PD). The medical records of patients admitted with PD and target
      symptoms were retrospectively reviewed. A total of 52 patients were treated over
      the 3 year period. Approximately 70% demonstrated an improvement in psychotic
      symptoms, but only 54% could also maintain mobility. Side-effects occurred in 37%
      of patients and consisted of decreased mobility, excessive sedation and excessive
      salivation. The drop out rate on follow-up was 47% so that at the end of the 3
      year period 23 patients still remained on the major tranquilliser from 44
      patients who were discharged on a major tranquilliser. The effectiveness of this
      approach is similar to that published for atypical major tranquillisers; however,
      the tranquillisers used in this study do not carry the risks of serious side
      effects or high cost.

PMID- 18639187
TI  - How long should a routine EEG be?
AB  - Cost-benefit analysis in neurology practice deserves continual reassessment. One
      example is the duration of a routine electroencephalography (EEG) required to
      optimise accuracy of diagnosis. Recommended guidelines of recording a routine EEG
      for 20 or more minutes are not based on scientific evidence. In many countries,
      EEG is not economically viable with costs outweighing financial remuneration. We
      prospectively studied 420 consecutive routine EEGs to see if a shorter record
      decreased diagnostic accuracy. A carefully structured 15 min routine EEG protocol
      produced comparable results with the 25 min recording. Shorter routine EEGs would
      make EEG more cost effective without compromising diagnostic accuracy.

PMID- 18639188
TI  - Neuro-ophthalmological signs during rapid intravenous administration of
      phenytoin.
AB  - We prospectively studied eye movement after rapid intravenous administration of
      phenytoin. Nineteen healthy young adults participated in a study of i.v.
      phenytoin pharmacokinetics. Subjects received a standard dose of 15 mg/kg at a
      rate of 25 mg/min, and were examined neuro-ophthalmologically before and at the
      end of the infusion. All patients had horizontal gaze-evoked nystagmus (HGN), and
      impairment of horizontal smooth pursuit (SP). Other signs were present in the
      following percentages: vertical gaze-evoked nystagmus (16 19 ,84%), and
      impairment of vertical SP (15 19 , 79%). Total and free phenytoin levels did not
      directly correlate with the degree of any of the neurological signs tested. By
      review of the past studies of nystagmus during phenytoin therapy, we propose that
      nystagmus is present consistently during toxicity with initial phenytoin therapy,
      but occurs less consistently during ongoing phenytoin use or chronic toxicity.

PMID- 18639189
TI  - Computer modelling of CSF flow in the subarachnoid space.
AB  - Computer modelling has been undertaken to determine the resistance to flow in the
      subarachnoid space (SAS) and to investigate its contribution to the total
      pressure drop. A Computational Fluid Dynamics model has been used to determine
      the pressure drop as a function of both the flow rate and the permeability of the
      subarachnoid space. The conclusion is that the SAS contributes about 1-5% of the
      total CSF flow resistance. However, scarring of the arachnoid fibres could
      increase the flow resistance considerably.

PMID- 18639190
TI  - Widespread early dendritic injury associated with loss of cortical MAP-2
      immunostaining in a focal ovine head impact model.
AB  - Dendritic pathology associated with traumatic brain injury may be identified by
      microtubule associated protein-2 (MAP-2) immunohistochemistry. The aim of this
      study was to examine the dendritic response in the cerebral cortical mantle in an
      ovine head impact model using MAP-2 immunostaining as a marker for dendritic
      injury. The loss of cortical MAP-2 immunoreactivity at 2 h was recorded and
      quantitated using a computerised image analysis system applied to standard
      coronal brain sections obtained from 10 impacted and 3 control sheep. Coup and
      contrecoup cortical contusions were present in 9 of 10 impacted brains examined 2
      h after injury. MAP-2 immunoreactivity was lost in all areas of cortical
      contusion irrespective of site and in otherwise histologically normal cortex. MAP
      2 immunostaining was lost in over 45% of the whole cortical area (range 32-54%)
      and only 2% (range 0-5.5%) was associated with contusions. This study has shown
      that there is widespread loss of MAP-2 immunostaining following head impact in
      the cerebral cortical mantle (up to 54%) suggestive of early dendritic injury.

PMID- 18639191
TI  - Concentration of brain free magnesium following severe brain injury correlates
      with neurologic motor outcome.
AB  - Recent studies have shown that brain intracellular free magnesium concentration
      significantly declines following mild to severe, focal and diffuse traumatic
      brain injury. However, little is known about how this decline or its attenuation
      by magnesium salts relates to neurologic outcome. This study uses phosphorus
      magnetic resonance spectroscopy and rotarod tests to characterise the
      relationship between brain free magnesium concentration and neurologic motor
      scores following severe, diffuse traumatic brain injury in rats. An intravenous
      bolus of MgSO(4) or MgCl(2) (100 mumoles/kg) at 30 min following brain injury
      significantly attenuated the postinjury brain free magnesium decline. This
      improved magnesium homeostasis was sustained for the entire postinjury monitoring
      period (1 week). There was an associated significant improvement in neurologic
      motor function in magnesium treated rats. Moreover, the brain free magnesium
      concentration over the one week period was linearly correlated with the
      neurologic motor function (r=0.70; P < 0.001) as assessed on a daily basis. We
      propose that brain free magnesium concentration may be used as a prognostic
      indicator of neurologic motor function after traumatic brain injury.

PMID- 18639192
TI  - Manubrial autograft for anterior cervical fusion.
AB  - Anterior cervical fusion is a commonly performed procedure and the most common
      graft material used is anterior iliac crest autograft. However, this donor site
      is a source of significant patient discomfort. The author describes the use of
      tricortical manubrial autograft which provides a surgically convenient donor site
      with less morbidity than with traditional iliac crest.

PMID- 18639193
TI  - Amnesia after basal forebrain damage due to anterior communicating artery
      aneurysm rupture.
AB  - A 53-year-old male presented with a subarachnoid haemorrhage secondary to an
      anterior communicating artery aneurysm rupture. The aneurysm was successfully
      treated with intravascular coiling. Post-haemorrhage the patient showed a
      profound amnestic syndrome with deficits in anterograde (and also retrograde)
      memory, confabulation and personality changes consistent with the anterior
      communicating artery syndrome (ACAS). Magnetic resonance imaging showed basal
      forebrain and orbitofrontal infarction. The patient was treated with donepezil (a
      cholinesterase inhibitor) without symptomatic improvement or clinically
      meaningful change in his psychometric testing. The clinical and
      neuropsychological features and the pathological basis of the ACAS are reviewed.

PMID- 18639194
TI  - Haemangiopericytoma of occipital bone with invasion of the transverse sinus.
AB  - A 44-year-old man presented with a painless left occipital mass which had
      enlarged over 4 months and was neurologically asymptomatic. Computed tomography
      and magnetic resonance imaging showed a large lytic tumour extending on both
      sides of the transverse sinus with intracranial and scalp extension. Angiography
      showed that the tumour was highly vascular. Preoperative embolisation of some of
      the main feeding vessels was performed, but a two-staged operation was needed for
      total removal of the tumour because of profuse bleeding from the tumour and bone.
      Histological examination disclosed numerous thin-walled 'staghorn' shaped
      capillaries and dense cellularity with atypical mitotic figures. The histological
      diagnosis was a primary haemangiopericytoma of the bone. He received external
      radiotherapy of 60 Gy. At 2 years follow-up, he remained well without recurrence.
      The optimal treatment for haemangiopericytoma is radical excision followed by
      radiation therapy. The need for long-term observation is emphasised because of
      the notorious tendency to recurrence and metastasis.

PMID- 18639195
TI  - Spontaneous spinal epidural haematoma in association with Kasabach-Merritt
      syndrome.
AB  - The authors report a case of spontaneous spinal epidural haematoma causing
      paraplegia secondary to thrombocytopaenia and consumptive coagulopathy from
      Kasabach-Merritt syndrome. The patient had long-standing multiple subcutaneous
      and visceral haemangiomas from childhood and developed lumbago and subsequent
      paraplegia. Evacuation of a spinal epidural haematoma was performed, however, the
      patient's neurological symptoms did not improve significantly. This case
      describes the potential risk of bleeding in the spinal column in patients with
      Kasabach-Merritt syndrome. Prompt diagnosis and management are crucial for an
      optimal outcome.

PMID- 18639196
TI  - Familial colloid cyst of the third ventricle.
AB  - We describe the cases of a mother and son who presented one year apart with a
      colloid cyst of the third ventricle. The mother was symptomatic and had complete
      resolution of her symptoms after surgical intervention. Her son was asymptomatic.
      There have been several reported instances of a familial association of colloid
      cysts of the third ventricle. The probability of a colloid cyst occurring in the
      same family coincidentally is possible, but highly unlikely (1 x 10(10)). The
      increasing number of reports of the familial incidence of colloid cysts would
      suggest the possibility of an autosomal dominant inheritance pattern, but to
      date, a familial pattern of inheritance has not been recognised. If there is a
      potential genetic link, then screening of asymptomatic relatives may be
      indicated. With non-invasive imaging techniques, such as computed tomography and
      magnetic resonance imaging scanning, accurate diagnosis and effective elective
      treatment is possible. This may result in preventing future complications as a
      result of hydrocephalus or sudden unexpected death, and also reduce morbidity as
      surgery can be done electively rather than as an emergency procedure.

PMID- 18639197
TI  - Paraplegia following surgery for medulloblastoma in the posterior fossa.
AB  - Postoperative paraplegia following non-spinal surgical procedures is very rare.
      We report a rare case of medulloblastoma in which paraplegia occurred after
      surgery. A 4-year-old boy suffered frequent vomiting and was found to have a
      tumour in the fourth ventricle associated with obstructive hydrocephalus. The
      tumour had already disseminated in the upper cervical spinal cord and thoracic
      cord. After surgical removal of the fourth ventricular tumour in the prone
      position, the patient developed paraplegia of the lower extremities. The cause of
      this complication may be the intraoperative patient position, overflexion of the
      neck, and/or imbalance of the subarachnoid pressure between rostral and caudal
      thoracic spinal cord by removing cerebrospinal fluid at the operative site. We
      report a rare complication of paraplegia associated with intracranial surgery.

PMID- 18639198
TI  - Fluctuating visual field defects in Rathke's cleft cysts: MRI analysis.
AB  - This is the first report that the authors are aware of concerning fluctuating
      visual field defects in patients with Rathke's cleft cysts. Among 11 patients
      with histologically proven Rathke's cleft cyst, three patients presented with a
      visual field defect which spontaneously resolved. The symptom became overt again
      in the subsequent 1 to 14 month follow-up period and a surgical procedure was
      then chosen. Magnetic resonance imaging (MRI) observation clearly revealed change
      in the cyst size without signal intensity change in two cases. In the remaining
      case, multiple spotty high intensities on T1-weighted images were found
      corresponding to fluctuations in the clinical course. In the last case,
      enlargement of the cyst was considered to be due to repeated haemorrhage. In the
      other two cases, minor haemorrhage, undetectable on MRI, may have played a role
      in the increased cyst size. Another possible mechanism is an imbalance between
      secretion from, and absorption into, the cyst wall. The size change and
      neurological fluctuations were previously unknown aspects of the natural history
      of this lesion. Surgical indications for such patients with transient symptoms
      followed by cyst size reduction have been controversial, since pituitary cystic
      lesions may enlarge again or disappear. Our observations suggest that this change
      in cyst size may be more frequently noted in cases with iso- or high intensity
      cysts on T1-weighted images, indicating the need for closer observation of
      patients with this MRI finding.

PMID- 18639199
TI  - Malignant transformation of craniopharyngioma.
AB  - Craniopharyngioma is a well recognised intracranial tumour; malignant
      transformation has been rarely described. In that case, malignant change occurred
      following irradiation for local recurrence and information is not provided on the
      biological behaviour of the tumour or the response to management. We report a
      further case of malignant transformation in recurrent craniopharyngioma following
      radiotherapy. The biological behaviour of malignant change in craniopharyngioma
      is uncertain so the treatment modalities require consideration of toxicity and
      other adverse sequelae balanced against anticipated outcome and comorbidities
      from previous treatments. The pathophysiology and therapeutic strategies are
      discussed. We review the possible pathogenic link between radiation therapy and
      malignant transformation.

PMID- 18639200
TI  - Neurolymphomatosis presenting as mononeuritis multiplex.
AB  - We report the case of a 60-year-old man who presented with a mononeuritis
      multiplex-type illness, beginning cranially and then sequentially involving
      peripheral nerves in all four limbs and torso. Despite extensive investigation,
      including multiple lumbar punctures and tissue biopsies, the diagnosis was not
      made until his death 10 months after presentation. Post mortem revealed
      lymphocytic infiltration of multiple peripheral nerves and radicules with minimal
      central nervous system involvement, consistent with neurolymphomatosis. Except
      for the pericardium, there was no other evidence of systemic lymphoma. Recent
      similar case reports highlight the value of magnetic resonance imaging of plexi
      and peripheral nerves, which may increase the chance of an antemortem diagnosis
      in this typically elusive disorder.

PMID- 18639201
TI  - Superficial siderosis of the central nervous system secondary to a thalamic
      hamartoma.
AB  - A patient with radiologically evident superficial siderosis of the central
      nervous system secondary to a thalamic hamartoma is reported. Cerebral hamartomas
      are rare, benign congenital lesions which when vascular can cause repeated
      subarachnoid haemorrhages, which results in deposition of iron (haemosiderin) in
      the leptomeninges and in the subpial layers of the brain and spinal cord.
      Progressive sensorineural deafness and cerebellar ataxia, which are typical
      clinical manifestations of superficial siderosis, may then appear. The importance
      of prompt diagnosis and treatment is highlighted.

PMID- 18639202
TI  - An algorithm for inferring complex haplotypes in a region of copy-number
      variation.
AB  - Recent studies have extensively examined the large-scale genetic variants in the
      human genome known as copy-number variations (CNVs), and the universality of CNVs
      in normal individuals, along with their functional importance, has been
      increasingly recognized. However, the absence of a method to accurately infer
      alleles or haplotypes within a CNV region from high-throughput experimental data
      hampers the finer analyses of CNV properties and applications to disease
      association studies. Here we developed an algorithm to infer complex haplotypes
      within a CNV region by using data obtained from high-throughput experimental
      platforms. We applied this algorithm to experimental data and estimated the
      population frequencies of haplotypes that can yield information on both sequences
      and numbers of DNA copies. These results suggested that the analysis of such
      complex haplotypes is essential for accurately detecting genetic differences
      within a CNV region between population groups.

PMID- 18639203
TI  - To the point: medical education review of the role of simulators in surgical
      training.
AB  - Simulation-based training (SBT) is becoming widely used in medical education to
      help residents and medical students develop good technical skills before they
      practice on real patients. SBT seems ideal because it provides a nonthreatening
      controlled environment for practice with immediate feedback and can include
      objective performance assessment. However, various forms of SBT and assessment
      often are being used with limited evidence-based data to support their validity
      and reliability. In addition, although SBT with high-tech simulators is more
      sophisticated and attractive, this is not necessarily superior to SBT with low
      tech (and lower cost) simulators. Therefore, understanding the types of surgical
      simulators and appropriate applications can help to ensure that this teaching and
      assessment modality is applied most effectively. This article summarizes the key
      concepts that are needed to use surgical simulators effectively for teaching and
      assessment.

PMID- 18639204
TI  - Oversight or Trompe l'oeil?

PMID- 18639205
TI  - The use of blunt needles does not reduce glove perforations during obstetrical
      laceration repair.
AB  - OBJECTIVE: The objective of the study was to compare the rate of glove
      perforation for blunt and sharp needles used during obstetrical laceration
      repair. A secondary aim was to assess physician satisfaction with blunt needles.
      STUDY DESIGN: This was an institutional review board-approved, randomized,
      prospective trial. Patients with obstetric lacerations were randomized to repair
      with either blunt or sharp needles. Patient demographics, operator experience,
      and other clinical variables were collected. Physicians reported any percutaneous
      injuries and were surveyed regarding satisfaction with the assigned needles.
      Glove perforation was determined using a validated water test method. RESULTS:
      There were 438 patients enrolled in the trial: 221 in the control group and 217
      in the study group. There was no statistical difference between groups in patient
      demographics, clinical variables, severity of laceration, or experience level of
      the surgeon. There was no difference in the glove perforation rate between blunt
      and sharp needles (risk ratio, 0.79; 95% confidence interval, 0.2-2.95). There
      was poor correlation between reported perforations and those detected by water
      test (R(2) = 0.33). The physicians reported that blunt needles were more
      difficult to use than sharp needles (P = .0001). CONCLUSION: There was no
      difference in the rate of surgical glove perforation for blunt, compared with
      sharp, needles used during vaginal laceration repair. Physicians also reported
      increased difficulty performing the repair with blunt needles.

PMID- 18639206
TI  - Effect of calcium ionophore A23187 on prostaglandin synthase type 2 and 15
      hydroxy-prostaglandin dehydrogenase expression in human chorion trophoblast
      cells.
AB  - OBJECTIVE: Prostaglandins induce parturition in humans. Prostaglandin output is
      regulated by the synthetic and metabolic enzymes, prostaglandin synthase type 2
      (PTGS2) and 15-hydroxyprostaglandin dehydrogenase (PGDH). The role of calcium in
      regulating PTGS2 and PGDH expression was investigated in chorion trophoblasts.
      STUDY DESIGN: Cells were treated with calcium ionophore A23187 in the presence or
      absence of calcium chelators; changes in messenger ribonucleic acid expression
      were measured with real-time polymerase chain reaction and analyzed with analysis
      of variance. Protein expression was evaluated with Western blot and dual
      immunofluorescence. RESULTS: A23187 stimulated PTGS2 and suppressed PGDH
      expression. Effects of A23187 were reversed by calcium chelators. PTGS2 had
      perinuclear and cytosolic distribution, whereas PGDH was cytosolic. Some cells
      expressed both enzymes, some neither enzyme, and some either PTGS2 or PGDH.
      CONCLUSION: Chorion cells showed heterogeneity in the expression of PTGS2 and
      PGDH. Calcium influx regulates PTGS2 and PGDH expression, thereby promoting
      coordinated increased prostaglandin output in circumstances such as term and
      preterm labor.

PMID- 18639207
TI  - Reoperation for urinary incontinence.
AB  - OBJECTIVE(S): The objective of the study was to describe the rate and associated
      factors of reoperation for urinary incontinence. STUDY DESIGN: A cohort study
      using Washington state hospitalization records from 1987 to 2005 of inpatient
      urinary incontinence surgeries. The cumulative reoperation rate was estimated for
      the entire cohort and by procedure. Cox regression was used to estimate the
      hazard of reoperation. RESULTS: A total of 41,705 women underwent either a sling
      or retropubic colposuspension (Burch); 1895 underwent reoperation for urinary
      incontinence (8.6%; 95% confidence interval, 7.8-9.5%), a rate of 5.5 per 1000
      woman-years. Women undergoing Burch had a lower reoperation rate than those
      undergoing slings (4.2 vs 6.7 per 1000 woman-years; P < .001). Concomitant
      hysterectomy was associated with a lower reoperation rate for Burch and sling
      repairs (5.4-2.9 and 7.7-4.2 per 1000 woman-years). CONCLUSION(S): Reoperation
      for urinary incontinence occurs commonly in the general population. The variable
      reoperation rate observed should be further investigated, given current trends
      toward increased Sling use.

PMID- 18639208
TI  - Effect of physician gender and specialty on utilization of hysterectomy in New
      York, 2001-2005.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of physician
      gender and specialty on the utilization of hysterectomy and alternatives to
      hysterectomy. STUDY DESIGN: The database of Empire Blue Cross Blue Shield was
      abstracted for all claims relating to a hysterectomy procedure or a hysterectomy
      associated diagnosis during the 48 consecutive months May 2001-April 2005. Two
      hundred ninety-five thousand, one hundred forty-eight claim lines were abstracted
      and analyzed by CPT and diagnostic grouping codes. RESULTS: One thousand nine
      hundred seventy-two hysterectomies were performed during the time analyzed, as
      well as 5077 hysterectomy alternatives. These 7049 procedures represented 2.4% of
      all coded physician encounters. Male physicians utilize hysterectomy and
      hysterectomy alternatives at the same rate as female physicians. Physicians who
      practice gynecology-only or gynecologic oncology utilize laparoscopically
      assisted vaginal hysterectomy more often than their counterparts who practice
      obstetrics as well as gynecology. CONCLUSION: Gender does not influence the rate
      of hysterectomy for similar clinical diagnoses. Subspecialty physicians utilize
      laparoscopic assisted vaginal hysterectomies more frequently than general
      obstetricians and gynecologists.

PMID- 18639209
TI  - Visually estimated and calculated blood loss in vaginal and cesarean delivery.
AB  - OBJECTIVE: The objective of the study was to compare visually estimated blood
      loss (vEBL) with calculated estimated blood loss (cEBL) according to mode of
      delivery and degree of perineal laceration. STUDY DESIGN: Pre- and postdelivery
      hematocrit (HCT) and other variables including vEBL were prospectively recorded
      into an obstetrical database between January and September 2005. The cEBL was
      derived by multiplying the calculated pregnancy blood volume (0.75 x {[maternal
      height (inches) x 50] + [maternal weight in pounds x 25]}) by percent of blood
      volume lost ({predelivery HCT - postdelivery HCT}/predelivery HCT). cEBL and vEBL
      were compared according to mode of delivery and degree of perineal laceration.
      RESULTS: There were 677 subjects with complete data. vEBL was statistically
      different from cEBL between each degree of laceration and between all modes of
      delivery, demonstrating an underestimation of vEBL with increasing cEBL.
      CONCLUSION: Improved methods for calculating blood loss include the use of a
      modified version of the formula used for pregnancy blood volume calculation.

PMID- 18639211
TI  - Increased neonatal mortality among normal-weight births beyond 41 weeks of
      gestation in California.
AB  - OBJECTIVE: The purpose of this study was to examine whether postterm gestational
      age increases the risk of neonatal mortality. STUDY DESIGN: We retrieved data
      from 1,815,811 liveborn infants in California from 1999 to 2003. We excluded
      multiple births and congenital anomalies, as well as infants with a gestational
      age of less than 38 w0d, or greater than 42 w6d, weeks. We used multivariable
      logistic regression models to adjust for demographic variables thought to
      confound the association. RESULTS: Compared to infants born at 38, 39, or 40
      weeks, those born at 41 w0d to 42 w6d have a greater odds of neonatal mortality
      (aOR: 1.34, 95% CI, 1.08-1.65). Subdividing by gestational week, infants
      delivered at 41 w0d to 41 w6d showed elevated mortality relative to earlier term
      births (aOR: 1.37, 95% CI, 1.08-1.73). Additional analyses support this increased
      neonatal mortality across all normal birthweight categories. CONCLUSION: Infants
      born beyond 41 w0d of gestation experience greater neonatal mortality relative to
      term infants born between 38 w0d and 40 w6d.

PMID- 18639213
TI  - Peripartum Clostridium difficile infection: case series and review of the
      literature.
AB  - Clostridium difficile infection (CDI) in nonhospitalized patients has been
      reported with increased frequency. An association between CDI and pregnancy has
      not been stressed. This review will report 4 cases of peripartum CDI with
      characterization of the infecting strain and a literature review. A PubMed search
      identified 24 recorded cases of peripartum CDI; information was available for 14
      cases. Most patients (91%) received prophylactic antibiotics during delivery or
      for treatment of bacterial infections (50%). All patients reported diarrhea. Two
      of our reported cases without known risk factors were found by polymerase chain
      reaction analysis to be infected with an epidemic and hypervirulent C difficile
      strain. These cases demonstrate the need for clinicians to consider CDI in
      patients with severe diarrhea, even if they do not have the traditional risk
      factors for CDI, such as antibiotic use or concurrent hospitalizations. Further
      research into the scope and risk factors for peripartum CDI is warranted.

PMID- 18639214
TI  - Advanced extrauterine pregnancy: diagnostic and therapeutic challenges.

PMID- 18639215
TI  - What is the definition of pulsatile umbilical venous flow in twin-twin
      transfusion syndrome?
AB  - OBJECTIVE: The aim of the study was to derive an objective definition of
      pulsatile umbilical venous flow (PUVF). STUDY DESIGN: Pulsed Doppler waveform
      analysis of the umbilical vein was performed in stages III and IV twin-twin
      transfusion syndrome (TTTS) patients. In patients with PUVF, the umbilical vein
      maximum (Vmax) and the umbilical vein minimum velocity (Vmin) and the resistance
      index for the umbilical vein (UVRI) = (100 x [Vmax - Vmin]/Vmax) were assessed.
      RESULTS: PUVF was noted in 130 of 226 stages III and IV TTTS patients. Digital
      images were available for analysis in 65 of 130 patients (50%). The minimum UVRI
      associated with PUVF was 16% for stages III and IV TTTS. There was a trend for
      increasing UVRI with stage (P = .052). Stage IV patients were more likely to have
      an UVRI greater than 30% (P = .02). CONCLUSION: PUVF can be defined as an UVRI
      greater than 15%. A scale definition of PUVF may further facilitate assessment of
      the degree of fetal hemodynamic compromise.

PMID- 18639216
TI  - Improving shoulder dystocia management among resident and attending physicians
      using simulations.
AB  - OBJECTIVE: The objective of the study was to determine whether a simulation-based
      educational program would improve residents' and attending physicians'
      performance in a simulated shoulder dystocia. STUDY DESIGN: Seventy-one
      obstetricians participated in an unanticipated simulated shoulder dystocia, an
      educational debriefing session, and a subsequent shoulder dystocia simulation.
      Each simulation was scored, based on standardized checklists for 4 technical
      maneuvers and 6 communication tasks, by 2 physician observers. Paired Student t
      tests were used for analysis. RESULTS: Forty-three attendings and 28 residents
      participated. Residents showed significant improvement in mean maneuver (3.3 +/-
      0.9 vs 3.9 +/- 0.4, P = .001) and communication (3.5 +/- 1.2 vs 4.9 +/- 1.0, P <
      .0001) scores after simulation training. Attending physicians' communication (3.6
      +/- 1.6 vs 4.9 +/- 1.1, P < .0001) scores were significantly improved after
      training. CONCLUSION: Our program improved physician performance in the
      management of simulated shoulder dystocia deliveries. Obstetric emergency
      simulation training can improve physicians' communication skills, at all levels
      of training, and should be incorporated into labor and delivery quality
      improvement measures.

PMID- 18639217
TI  - Chorionic villus sampling and the risk of adverse outcome in patients undergoing
      multifetal pregnancy reduction.
AB  - OBJECTIVE: The objective of the study was to determine whether patients
      undergoing chorionic villus sampling (CVS) prior to MPR are at increased risk for
      adverse outcome compared to those who did not. STUDY DESIGN: We retrospectively
      identified multifetal pregnancy reduction (MPR) patients from an established
      database. Maternal demographic data were collected. Outcomes including complete
      pregnancy loss prior to 24 weeks' gestation, gestational age at delivery, and
      birthweight were analyzed. RESULTS: There was no significant difference in
      pregnancy loss between the 2 groups (CVS [4%] vs no CVS [7%], P = .098). When
      stratified by finishing number, there was a significantly lower loss rate in the
      singleton CVS group (2% vs 9%, P = .025) and no significant difference in reduced
      twins. There was no significant difference in the average gestational age of
      delivery or birthweight. CONCLUSION: CVS prior to MPR does not increase the risk
      of pregnancy loss. Our data suggest that CVS prior to singleton reduction may
      decrease the risk of adverse outcome.

PMID- 18639218
TI  - Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal
      transcription and growth factor expression.
AB  - OBJECTIVE: Maternal food restriction during pregnancy results in growth
      restricted newborns and reduced glomerular number, contributing to programmed
      offspring hypertension. We investigated whether reduced nephrogenesis may be
      programmed by dysregulation of factors controlling ureteric bud branching and
      mesenchyme to epithelial transformation. STUDY DESIGN: At 10 to 20 days'
      gestation, Sprague Dawley pregnant rats (n = 6/group) received ad libitum food;
      food-restricted rats were 50% food restricted. At embryonic day 20, messenger
      ribonucleic acid (mRNA) and protein expression of Wilms' tumor 1 gene product
      (WT1), paired box transcription factor (Pax)-2, fibroblast growth factor (FGF)-2,
      glial cell line-derived neurotrophic factor (GDNF), cRET, wingless-type mouse
      mammary tumor virus integration site (WNT)4, WNT11, bone morphogenetic protein
      (BMP)-4, BMP7, and FGF7 were determined by real-time polymerase chain reaction
      and Western blotting. RESULTS: Maternal food restriction resulted in up-regulated
      mRNA expression for WT1, FGF2, and BMP7, whereas Pax2, GDNF, FGF7, BMP4, WNT4,
      and WNT11 mRNAs were down-regulated. Protein expression was concordant for WT1,
      GDNF, Pax2, FGF7, BMP4, and WNT4. CONCLUSION: Maternal food restriction altered
      gene expression of fetal renal transcription and growth factors and likely
      contributes to development of offspring hypertension.

PMID- 18639219
TI  - Enhanced depth imaging spectral-domain optical coherence tomography.
AB  - PURPOSE: To describe a method to obtain images of the choroid using conventional
      spectral-domain (SD) optical coherence tomography (OCT) and to evaluate choroidal
      thickness measurements using these images. DESIGN: Observational case series.
      METHODS: The images were obtained by positioning the SD OCT device close enough
      to the eye to obtain an inverted representation of the fundus in healthy
      volunteers who did not have pupillary dilation. Seven sections, each comprised of
      100 averaged scans, were obtained within a 5- x 15-degree rectangle centered on
      the fovea. The choroidal thickness under the fovea in each image was measured by
      independent observers. RESULTS: The choroidal thickness could be evaluated in
      every subject's choroidal image. The mean choroidal thickness under the fovea was
      318 microm in the right eye and 335 microm in the left eye. The choroidal
      thickness showed a high correlation in both eyes (r = 0.82; P < .001). The
      correlation between the measurements performed by the independent observers was
      highly significant (right eye, r = 0.93; left eye, r = 0.97; P < .001 for both).
      CONCLUSIONS: This method provides detailed, measurable images from the choroid, a
      structure that heretofore has been difficult to image in clinical practice.

PMID- 18639220
TI  - Combined fluocinolone acetonide intraocular delivery system insertion,
      phacoemulsification, and intraocular lens implantation for severe uveitis.
AB  - PURPOSE: To determine whether a three-year fluocinolone acetonide sustained drug
      delivery system can be implanted safely at the same time that phacoemulsification
      and intraocular lens (IOL) implantation are performed for a visually significant
      cataract in eyes with uveitis. DESIGN: Retrospective, single-center case series.
      METHODS: All consecutive patients treated from April 1998 through September 2006
      at an academic clinical practice with intermediate uveitis, posterior uveitis, or
      panuveitis requiring immunosuppressive therapy, periocular corticosteroid
      injections, or both. Phacoemulsification, IOL implantation, and fluocinolone
      acetonide implant insertion were performed during a single surgical session. The
      main outcome measures were preoperative and postoperative ocular inflammation,
      visual acuity (VA), intraoperative complications, anti-inflammatory medication
      use, IOP, and postoperative adverse events. RESULTS: Twenty-four eyes of 21
      patients were studied. Mean follow-up duration was 27 months (range, six to 60
      months). No patients had intraoperative complications. The mean Snellen VA at
      baseline was 20/316, which improved significantly to 20/75 at 12 months. The
      average number of recurrences in the 12 months before implantation was 2.2
      episodes per eye. Only one eye experienced a recurrence at seven months after
      implantation. Topical corticosteroids, posterior sub-Tenon capsule injections,
      and systemic anti-inflammatory medications were reduced significantly at 12
      months. Average IOP was unchanged after surgery compared with preoperative IOP;
      15% underwent glaucoma filtering surgery. CONCLUSIONS: A fluocinolone acetonide
      implant insertion can be combined safely with phacoemulsification plus IOL
      implantation during the same surgical session in eyes with uveitis. VA generally
      was improved, uveitis recurrences decreased, and the need for immunosuppression
      decreased. The most common side effect was increased IOP.

PMID- 18639221
TI  - A prospective randomized controlled trial of simple Bascom's technique versus
      Bascom's cleft closure for the treatment of chronic pilonidal disease.
AB  - BACKGROUND: The aim of this study was to determine which of Bascom's simple
      techniques, Bascom's simple surgery or Bascom's cleft closure, is preferred in
      the management of moderate-severity pilonidal disease. METHODS: Fifty-five
      patients with chronic pilonidal disease were randomized to receive Bascom's
      simple surgery (n = 29) or cleft closure (n = 26) under local anesthetic. The
      primary end point was time to healing. Patients were followed up for a median of
      3 years (range, .7-4 y). RESULTS: After Bascom's simple surgery, 5 of 29 patients
      did not heal and proceeded to cleft closure. The remaining patients healed at a
      median of 4 weeks (range, 3-35 wk). After cleft closure, 21 of 26 wounds healed
      primarily on removal of sutures at 10 to 13 days. The remaining 5 wounds healed
      at a median of 4.5 weeks (range, 2-5 wk). Fifty of 55 (91%) patients were
      contacted for follow-up evaluation, disease recurrence occurred in 2 of 24 after
      Bascom's simple surgery and in 0 of 26 after cleft closure. CONCLUSIONS: Cleft
      closure offers more predictable healing than Bascom's simple surgery, with less
      need for re-operation. Disease recurrence is more prevalent after Bascom's simple
      surgery.

PMID- 18639222
TI  - Decreased bile acid synthesis with total parenteral nutrition.

PMID- 18639223
TI  - Do the risks of emergent colectomy justify nonoperative management strategies for
      recurrent diverticulitis?
AB  - BACKGROUND: The nonoperative approach to recurrent and even multiple recurrent
      diverticulitis has recently been advocated. This approach, however, may result in
      more frequent acute attacks requiring emergent colectomy. Our aim was to compare
      the colectomy outcomes for diverticulitis in the elective and acute settings.
      METHODS: All patients with diverticulitis undergoing elective (EL) and emergent
      (EM) colectomy selected from the 2001 to 2002 Nationwide Inpatient Sample
      Database were analyzed and compared. RESULTS: Five thousand ninety-seven (27.1%
      emergent) colectomy cases were analyzed. EL patients had a significantly reduced
      length of stay (7.5 vs 13.3 days) and total hospital charges ($25,420 vs
      $51,170). Postsurgical morbidity and mortality were significantly higher in the
      EM group (29.0% vs 14.9% and 7.4% vs .8%, respectively). Colostomy was needed in
      5.7% of EL and in 48.9% of EM patients (P = .001). CONCLUSIONS: Emergent
      colectomy in the setting of diverticulitis is associated with significantly
      higher morbidity, longer hospitalization, greater hospital charges, and a 9-fold
      increase in mortality. Prophylactic resection in the setting of recurrent
      diverticulitis should continue to be an acceptable and possibly more
      "conservative" approach.

PMID- 18639224
TI  - Renal artery aneurysms in kidney grafts.
AB  - The shortage of organs has forced transplant surgeons to use grafts from marginal
      donors, even those presenting with important vascular alterations. In such cases,
      in-depth knowledge of the vascular anatomy and its variants, the correct
      identification and preservation of the arterial supply, and familiarity with
      microsurgical techniques for vascular reconstruction are mandatory. Renal artery
      aneurysms (RAAs) are an uncommon entity whose incidence is approximately .01%
      .09% in the general population and .7%-.9% in subjects undergoing angiographic
      investigation. When present in renal grafts, they can be resected at the back
      table and the graft can be successfully implanted.

PMID- 18639225
TI  - Hepatic parenchymal transection with vascular staplers: a comparative analysis
      with the crush-clamp technique.
AB  - BACKGROUND: This retrospective study compares the safety and efficacy of hepatic
      parenchymal transection using vascular staplers (VS) and the crush-clamp (CC)
      technique. METHODS: Demographics, clinicopathologic data, treatments, and
      postoperative outcomes from patients who underwent VS or CC hepatic parenchymal
      transection were compared. RESULTS: From 1996-2006, 99 and 112 patients underwent
      hepatic transection with VS and CC, respectively. Compared to CC, VS transection
      was associated with less operative time (median 210 vs 275 minutes), blood loss
      (median 250 vs 500 mL), and postoperative red blood cell (RBC) transfusion (29%
      vs 44%), all P < .05. VS transection was not associated with RBC transfusion on
      multivariate analysis. There were no differences in rates of positive resection
      margins (9% vs 13%), postoperative mortality (2% vs 4%), overall morbidity (32%
      vs 29%), and severe morbidity (20% vs. 23%), all P > .05. CONCLUSION: Hepatic
      parenchymal transection with VS can be accomplished with similar safety and
      efficacy as CC transection.

PMID- 18639226
TI  - Inguinal hernioplasty improves the quality of life in patients with cirrhosis.
AB  - BACKGROUND: The optimal management of symptomatic inguinal hernia (SIH) in
      cirrhotics is still undefined. Both hernia and cirrhosis impair quality of life
      (QOL). The aim of this study was to evaluate QOL by a Short Form-36 (SF-36)
      questionnaire in cirrhotic patients undergoing inguinal hernioplasty. METHODS:
      Thirty-two cirrhotic patients undergoing inguinal hernioplasty were evaluated.
      They were classified according to Child's class and to the absence or presence of
      refractory ascites. The SF-36 questionnaire was administered the day before and 6
      months after surgery. Global analyses of the 8 domains of SF-36 and of 2
      comprehensive indexes of SF-36, Physical Component Summary (PCS) and Mental
      Component Summary (MCS), were performed. RESULTS: Lichtenstein hernioplasty for
      SIH originated no major complications. All 8 domains of SF-36 and MCS and PCS
      scores improved remarkably after hernioplasty especially in patients in Child's
      class C and/or with refractory ascites. CONCLUSIONS: Inguinal hernioplasty for
      SIH in patients with cirrhosis is a safe procedure. The improvement of QOL
      represents a clear cut indication for elective hernia repair.

PMID- 18639227
TI  - Diagnosis of papillary lesions in breast biopsy: is conservative management
      justified?

PMID- 18639228
TI  - Impact of surgery on immunologic function: comparison between minimally invasive
      techniques and conventional laparotomy for surgical resection of colorectal
      tumors.
AB  - BACKGROUND: Surgical trauma suppresses host immune function, potentially creating
      an environment vulnerable to tumor cell growth. This study compared immune
      function after laparoscopy, minilaparotomy, and conventional colorectal tumor
      resections. METHODS: Seventy-one patients underwent surgery (20 laparoscopy, 21
      minilaparotomy, and 30 conventional). Blood samples were taken before surgery and
      at 3 hours, 24 hours, and 5 days after surgery. White blood cell constitution was
      determined using monoclonal antibodies. Levels of TH1 cytokines interferon-gamma,
      tumor necrosis factor-alpha, and interleukin (IL)-2 and TH2 cytokines IL-10, -4,
      and -6 were measured in plasma and from supernatants of activated peripheral
      blood mononuclear cells. RESULTS: At 5 days after surgery, lymphocyte counts
      remained low in the conventional and minilaparotomy groups (P = .001 and P =
      .008) but had resolved in laparoscopic patients. Three-hour postoperative serum
      IL-6 concentrations were lower in laparoscopic than in conventional patients (P =
      .028). Production of TH1 cytokines 3 hours after surgery were significantly
      increased in laparoscopic patients (interferon-gamma P = .018, tumor necrosis
      factor-alpha P = .011, and IL-2 P = .037). CONCLUSIONS: TH1 lymphocyte function
      is improved transiently and immune homeostasis restored earlier in patients
      undergoing laparoscopic colorectal cancer resection, which may influence disease
      recurrence.

PMID- 18639229
TI  - Preoperative platelet-lymphocyte ratio is an independent significant prognostic
      marker in resected pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: The objective of this study was to investigate whether the
      preoperative platelet-lymphocyte (P/L) ratio represents a significant prognostic
      index in resected pancreatic ductal adenocarcinoma. METHODS: A total of 110
      patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma
      over a 10-year period were identified from a prospectively maintained database.
      RESULTS: The preoperative P/L ratio was found to be a more significant prognostic
      marker (P < .001) than either the lymphocyte count (P = .007) or platelet count
      (P = .068) on univariate Cox survival analysis. The median overall survival in
      patients with a P/L ratio of 150 or less (n = 48) was 19.7 months, 13.7 months in
      those with a P/L ratio of 151 to 300 (n = 43), and 5.8 months in patients with a
      value of greater than 300 (n = 19) (log-rank, P = .006). The preoperative P/L
      ratio retained significance on multivariate analysis (P < .001), along with tumor
      size (P = .010) and lymph node ratio (P = .013). CONCLUSIONS: The preoperative
      P/L ratio represents a significant independent prognostic index in patients of
      resected pancreatic adenocarcinoma.

PMID- 18639230
TI  - Two-surgeon technique using saline-linked electric cautery and ultrasonic
      surgical aspirator in living donor hepatectomy: its safety and efficacy.
AB  - BACKGROUND: Saline-linked electric cautery (SLC) is introduced as an effective
      device to reduce blood loss in liver surgery. The aim of the current study was to
      evaluate the safety and efficacy of a 2-surgeon technique using SLC and the
      Cavitron Ultrasonic Surgical Aspirator (CUSA; Valleylab, Boulder, CO) in living
      donor hepatectomy. METHODS: Forty-three living donor right hepatectomy cases were
      enrolled in this study. The first 28 cases underwent liver transection with CUSA
      alone (CUSA group), while additional SLC was applied in the current 15 cases (2
      surgeon technique, TS group). RESULTS: Blood loss was significantly reduced by
      the 2-surgeon technique (1,115.2 +/- 652.9 g in CUSA group vs 732.3 +/- 363.6 g
      in TS group, P < .05). In the TS group, there was no bile leakage from the cut
      surface. The early graft function and postoperative recipient survival were not
      significantly different between the groups. CONCLUSIONS: According to our single
      center experience, blood loss and donor complications in living donor
      hepatectomies were significantly reduced using a 2-surgeon technique using CUSA
      and SLC, while maintaining the graft viability.

PMID- 18639231
TI  - Race does not impact colorectal cancer treatment or outcomes with equal access.
AB  - BACKGROUND: Ethnicity is implicated as a factor for disparate outcomes in
      colorectal cancer. We sought to evaluate this relationship at a military medical
      center organized to deliver equitable health care. METHODS: Retrospective
      analysis of colorectal cancer patients comparing demographics, grade, American
      Joint Committee on Cancer (AJCC) stage, and adjuvant therapy. RESULTS: From
      January 1994 to January 2004, 398 patients were treated with colorectal cancer
      (74 [19%] nonwhites). Comparatively, nonwhites were younger and had fewer stage
      II tumors with a increased proportion of stage III tumors (P < .01). With a
      median follow-up period of 52 (0-151) months, there were no disparities in
      surgical resection, adjuvant therapy, or disease recurrence. Kaplan-Meier
      analysis revealed no disparity in disease-free and cancer-specific survival (P =
      .585 and P = .132); Cox regression revealed increased age and AJCC stage III as
      the only independent predictors of lower survival (P < .05). CONCLUSIONS:
      Ethnicity was associated with differences in age and AJCC stage at presentation.
      In an equitable health care system, these differences did not impact patients'
      treatment or survival.

PMID- 18639232
TI  - Single-stage closure of enterocutaneous fistula and stomas in the presence of
      large abdominal wall defects using the components separation technique.
AB  - BACKGROUND: Closure of an enterocutaneous fistula and/or stomas in the presence
      of large abdominal wall defects is a challenging problem. In the present study,
      the results of the components separation technique are described. METHODS: All
      patients with an enterocutaneous fistula and/or stomas in the presence of large
      abdominal wall defects (ie, laparostomy of ventral hernia) who underwent a single
      stage repair using the components separation technique in the period from January
      2000 to July 2007 were reviewed retrospectively. RESULTS: A total of 32 patients
      were included. The median operating time was 204 minutes (range 87-573). In 18
      patients, additionally to the components separation, an absorbable mesh was used.
      Postoperatively, in 16 patients 22 complications were reported. There were 9
      patients with local wound problems. The median postoperative hospital stay was 12
      days (range 5-74). Seven patients developed a ventral hernia. Four of them were
      small asymptomatic recurrences. Four out of the 15 patients with an
      enterocutaneous fistula developed a recurrent fistula. The median follow-up was
      20 months (range 3-54). CONCLUSION: Closure of enterocutaneous fistula and/or
      stomas and simultaneous repair of large abdominal wall defects is feasible using
      the components separation technique but morbidity is considerable. Early
      recurrence of abdominal hernia and fistula is acceptable.

PMID- 18639234
TI  - Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant
      depression.
AB  - BACKGROUND: A preliminary report in six patients suggested that deep brain
      stimulation (DBS) of the subcallosal cingulate gyrus (SCG) may provide benefit in
      treatment-resistant depression (TRD). We now report the results of these and an
      additional 14 patients with extended follow-up. METHODS: Twenty patients with TRD
      underwent serial assessments before and after SCG DBS. We determined the
      percentage of patients who achieved a response (50% or greater reduction in the
      17-item Hamilton Rating Scale for Depression [HRSD-17]) or remission (scores of 7
      or less) after surgery. We also examined changes in brain metabolism associated
      with DBS, using positron emission tomography. RESULTS: There were both early and
      progressive benefits to DBS. One month after surgery, 35% of patients met
      criteria for response with 10% of patients in remission. Six months after
      surgery, 60% of patients were responders and 35% met criteria for remission,
      benefits that were largely maintained at 12 months. Deep brain stimulation
      therapy was associated with specific changes in the metabolic activity localized
      to cortical and limbic circuits implicated in the pathogenesis of depression. The
      number of serious adverse effects was small with no patient experiencing
      permanent deficits. CONCLUSIONS: This study suggests that DBS is relatively safe
      and provides significant improvement in patients with TRD. Subcallosal cingulate
      gyrus DBS likely acts by modulating brain networks whose dysfunction leads to
      depression. The procedure is well tolerated and benefits are sustained for at
      least 1 year. A careful double-blind appraisal is required before the procedure
      can be recommended for use on a wider scale.

PMID- 18639233
TI  - An association analysis of murine anxiety genes in humans implicates novel
      candidate genes for anxiety disorders.
AB  - BACKGROUND: Human anxiety disorders are complex diseases with largely unknown
      etiology. We have taken a cross-species approach to identify genes that regulate
      anxiety-like behavior with inbred mouse strains that differ in their innate
      anxiety levels as a model. We previously identified 17 genes with expression
      levels that correlate with anxiety behavior across the studied strains. In the
      present study, we tested their 13 known human homologues as candidate genes for
      human anxiety disorders with a genetic association study. METHODS: We describe an
      anxiety disorder study sample derived from a Finnish population-based cohort and
      consisting of 321 patients and 653 carefully matched control subjects, all
      interviewed to obtain DSM-IV diagnoses. We genotyped altogether 208 single
      nucleotide polymorphisms (SNPs) (all non-synonymous SNPs, SNPs that alter
      potential microRNA binding sites, and gap-filling SNPs selected on the basis of
      HapMap information) from the investigated anxiety candidate genes. RESULTS:
      Specific alleles and haplotypes of six of the examined genes revealed some
      evidence for association (p < or = .01). The most significant evidence for
      association with different anxiety disorder subtypes were: p = .0009 with ALAD
      (delta-aminolevulinate dehydratase) in social phobia, p = .009 with DYNLL2
      (dynein light chain 2) in generalized anxiety disorder, and p = .004 with PSAP
      (prosaposin) in panic disorder. CONCLUSIONS: Our findings suggest that variants
      in these genes might predispose to specific human anxiety disorders. These
      results illustrate the potential utility of cross-species approaches in
      identification of candidate genes for psychiatric disorders.

PMID- 18639235
TI  - The kappa-opioid agonist U69,593 blocks cocaine-induced enhancement of brain
      stimulation reward.
AB  - BACKGROUND: Increasing evidence indicates that brain kappa-opioid receptors
      (KORs) are involved in regulation of mood states. In animal models often used to
      study psychiatric illness, KOR agonists produce depressive-like effects (e.g.,
      anhedonia), whereas KOR antagonists produce antidepressant- and anxiolytic-like
      effects. The ability of KOR agonists to produce anhedonia-like signs in
      laboratory animals raises the possibility that this class of drugs might be
      useful to ameliorate states characterized by excess reward or motivation, such as
      mania or stimulant intoxication. METHODS: We examined how the selective KOR
      agonist U69,593 affects cocaine-induced facilitation of intracranial self
      stimulation (ICSS), a model of the abnormally increased reward function that
      characterizes mania and stimulant intoxication. Rats with stimulating electrodes
      implanted in the medial forebrain bundle (MFB) were tested with intraperitoneal
      injections of U69,593 (.063-.5 mg/kg) alone, cocaine (1.25-10 mg/kg) alone, and
      combinations of the drugs. RESULTS: Cocaine dose-dependently decreased ICSS
      thresholds, indicating that it enhanced the rewarding impact of MFB stimulation.
      In contrast, U69,593 dose-dependently increased ICSS thresholds, indicating that
      it decreased the rewarding impact of the stimulation. Pretreatment with U69,593
      blocked cocaine-induced decreases in ICSS thresholds at doses that had negligible
      effects on their own. CONCLUSIONS: Activation of KORs reduces the reward-related
      effects of cocaine. Inasmuch as cocaine-induced behavioral stimulation in rodents
      may model key aspects of enhanced mood in humans, these findings raise the
      possibility that KOR agonists might ameliorate symptoms of conditions
      characterized by increased motivation and hyperfunction of brain reward systems,
      such as mania and stimulant intoxication.

PMID- 18639236
TI  - Functional activation and neural networks in women with posttraumatic stress
      disorder related to intimate partner violence.
AB  - BACKGROUND: Intimate partner violence (IPV) is one of the most common causes of
      posttraumatic stress disorder (PTSD) in women. Victims of IPV are often
      preoccupied by the anticipation of impending harm. This investigation tested the
      hypothesis that IPV-related PTSD individuals show exaggerated insula reactivity
      to the anticipation of aversive stimuli. METHODS: Fifteen women with a history of
      IPV and consequent PTSD (IPV-PTSD) and 15 non-traumatized control (NTC) women
      performed a task involving cued anticipation to images of positive and negative
      events during functional magnetic resonance imaging. RESULTS: Both groups showed
      increased activation of bilateral anterior insula during anticipation of negative
      images minus anticipation of positive images. Activation in right anterior/middle
      insula was significantly greater in the IPV-PTSD relative to the NTC group.
      Functional connectivity analysis revealed that changes in activation in right
      middle insula and bilateral anterior insula were more strongly associated with
      amygdala activation changes in NTC than in IPV-PTSD subjects. CONCLUSIONS: This
      study revealed increased activation in the anterior/middle insula during negative
      anticipation in women with IPV-related PTSD. These findings in women with IPV
      could be a consequence of the IPV exposure, reflect pre-existing differences in
      insular function, or be due to the development of PTSD. Thus, future longitudinal
      studies need to examine these possibilities.

PMID- 18639238
TI  - Anatomic abnormalities of the anterior cingulate cortex before psychosis onset:
      an MRI study of ultra-high-risk individuals.
AB  - BACKGROUND: Abnormalities of the anterior cingulate cortex (ACC) are frequently
      implicated in the pathophysiology of psychotic disorders, but whether such
      changes are apparent before psychosis onset remains unclear. In this study, we
      characterized prepsychotic ACC abnormalities in a sample of individuals at ultra
      high-risk (UHR) for psychosis. METHODS: Participants underwent baseline magnetic
      resonance imaging and were followed-up over 12-24 months to ascertain diagnostic
      outcomes. Baseline ACC morphometry was then compared between UHR individuals who
      developed psychosis (UHR-P; n = 35), those who did not (UHR-NP; n = 35), and
      healthy control subjects (n = 33). RESULTS: Relative to control subjects, UHR-P
      individuals displayed bilateral thinning of a rostral paralimbic ACC region that
      was negatively correlated with negative symptoms, whereas UHR-NP individuals
      displayed a relative thickening of dorsal and rostral limbic areas that was
      correlated with anxiety ratings. Baseline ACC differences between the two UHR
      groups predicted time to psychosis onset, independently of symptomatology.
      Subdiagnostic comparisons revealed that changes in the UHR-P group were driven by
      individuals subsequently diagnosed with a schizophrenia spectrum psychosis.
      CONCLUSIONS: These findings indicate that anatomic abnormalities of the ACC
      precede psychosis onset and that baseline ACC differences distinguish between UHR
      individuals who do and do not subsequently develop frank psychosis. They also
      indicate that prepsychotic changes are relatively specific to individuals who
      develop a schizophrenia spectrum disorder, suggesting they may represent a
      diagnostically specific risk marker.

PMID- 18639237
TI  - Glial loss in the prefrontal cortex is sufficient to induce depressive-like
      behaviors.
AB  - BACKGROUND: Postmortem studies have repeatedly found decreased density and number
      of glia in cortical regions, including the prefrontal and cingulate areas, from
      depressed patients. However, it is unclear whether this glial loss plays a direct
      role in the expression of depressive symptoms. METHODS: To address this question,
      we characterized the effects of pharmacologic glial ablation in the prefrontal
      cortex (PFC) of adult rats on behavioral tests known to be affected by stress or
      antidepressant treatments: sucrose preference test (SPT), novelty suppressed
      feeding test (NSFT), forced swim test (FST), and two-way active avoidance test
      (AAT). We established the dose and time course for the actions of an astrocyte
      specific toxin, L-alpha-aminoadipic acid (L-AAA), and compared the behavioral
      effects of this gliotoxin with the effects of an excitotoxic (ibotenate) lesion
      and to the effects of chronic stress. RESULTS: The results demonstrate that L-AAA
      infusions induced anhedonia in SPT, anxiety in NSFT, and helplessness in FST and
      AAT. These effects of L-AAA were similar to chronic unpredictable stress (CUS)
      induced depressive-like behaviors in these tests. However, ibotenate-induced
      neurotoxic lesion of the PFC had no effect in these behavioral tests.
      CONCLUSIONS: The results demonstrate that glial ablation in the PFC is sufficient
      to induce depressive-like behaviors similar to chronic stress and support the
      hypothesis that loss of glia contributes to the core symptoms of depression.

PMID- 18639239
TI  - Major depression affects perceptual filling-in.
AB  - BACKGROUND: Major depression disorder is a syndrome that involves impairment of
      cognitive functions such as memory, attention, and plasticity. In this study, we
      explored whether depression affects perception as well. METHODS: We used a
      recently developed paradigm that assesses the filling-in process by probing false
      positive reports (false alarm [FA]), hit rates (pHit), sensitivity (d'), and
      decision criteria (Cr). We used a Yes-No paradigm in a low-level detection task
      involving a Gabor target, in the presence of collinear flankers, inducing filling
      in, with differing target-flanker separations of 3-15 lambda(wavelength). The
      depressive state of patients was assessed using the Hamilton Depression Rating
      Scale. Two groups were tested: an experimental group with major depression (n =
      27) and a control group (n = 32). RESULTS: The performances of the control and
      the experimental groups were not significantly different regarding d'. In
      contrast, a specific pattern of significant differences between the control group
      and the hospitalized group was found for the decision criterion, pHit, and pFA,
      but only for target-flanker separations of 3 lambda, whereas the results for the
      other separations were insignificant. The differences between the control and the
      depressed groups are not due to a global cognitive dysfunction in depression.
      CONCLUSIONS: The results suggest that the filling-in process is deficient,
      probably because of reduced excitation among neurons. Neural excitation is a key
      factor in the neural processing involved in memory and decision making. In
      addition, it is still possible that the patients may be unable to match their
      internal representation to the changing sensory information.

PMID- 18639240
TI  - Chemical preparation of sialyl Lewis x using an enzymatically synthesized
      sialoside building block.
AB  - The sialyl Lewis x tetrasaccharide with a propylamine aglycon was assembled by
      chemoselective glycosylation from a p-tolyl thioglycosyl donor obtained from an
      enzymatically synthesized sialodisaccharide. Combining the advantages of highly
      efficient enzymatic synthesis of sialoside building blocks, and diverse chemical
      glycosylation, this chemoenzymatic approach is practical for obtaining complex
      sialosides and their analogues.

PMID- 18639241
TI  - Reinvestigation of the O-antigens of Yersinia pseudotuberculosis: revision of the
      O2c and confirmation of the O3 antigen structures.
AB  - Structures of the O-antigens of Yersinia pseudotuberculosis O2c and O3 were
      reinvestigated by NMR spectroscopy, including 2D (1)H,(1)H COSY, TOCSY, ROESY,
      (1)H,(13)C HSQC, and HMBC experiments. The following revised structure of the O2c
      tetrasaccharide repeating unit was established, which differs from the structure
      proposed earlier in the glycosylation pattern of the mannose residue at the
      branching point: [carbohydrate structure: see text] where Abe stands for 3,6
      dideoxy-d-xylo-hexose. The structure of the Y. pseudotuberculosis O3 antigen
      reported earlier was confirmed.

PMID- 18639242
TI  - Measuring urinary testosterone levels of the great apes--problems with enzymatic
      hydrolysis using Helix pomatia juice.
AB  - Helix pomatia (Hp) juice is a common enzymatic preparation for deconjugation of
      urinary steroids. It has been used in many published studies on urinary
      testosterone (T) in chimpanzees and bonobos, although the ability of Hp juice to
      convert other urinary steroids into T has been reported for human urine. We
      developed a protocol for determination of reliable T levels in primate urine
      using liquid chromatography-mass spectrometry. T levels were determined in a set
      of human, bonobo and chimpanzee urine samples (A) by measurement of intact
      testosterone glucuronide (TG) and testosterone sulfate (TS), (B) after
      hydrolysis/solvolysis with beta-glucuronidase from Hp and (C) from Escherichia
      coli. When samples were hydrolyzed with Hp juice, results were not correlated
      with the direct assay of TG and TS, and determined T concentrations were
      considerably higher. By contrast, hydrolysis with E. coli beta-glucuronidase
      yielded a good agreement of T concentrations. We demonstrated the ability of Hp
      juice to convert androst-5-ene-3beta, 17beta-diol (A(5)diol) into T using
      commercial standards and within the urine of all three species. As A(5)diol
      usually is present at higher levels in urine than T, this artifact leads to
      erroneous results for T concentrations in primate urine. The proportion of T
      excreted as sulfate (TS) is often neglected as TS can only be cleaved by
      additional solvolysis. In all three species, we found substantial amounts of TS
      in the urine of some subjects and a high variance of TS proportion between and
      within subjects. Therefore the inclusion of solvolysis into the sample
      preparation seems necessary.

PMID- 18639243
TI  - Gitelman syndrome in pregnancy.

PMID- 18639244
TI  - Linear solvation energy relationships of anionic dimeric surfactants in micellar
      electrokinetic chromatography III. Effect of fluorination.
AB  - The range of selectivities of pseudostationary phases (PSPs) available for
      micellar electrokinetic chromatography is limited, and there continues to be
      interest in the synthesis and evaluation of novel PSPs. With the unique
      selectivity of lithium perfluorooctanesulfonate (LPFOS) in mind, we synthesized
      anionic dimeric surfactants with fluorinated spacers of various lengths. Their
      selectivities, analyzed via linear solvation energy relationships, are similar to
      those of their non-fluorinated analogues, although the results indicated that
      they are somewhat less polarizable. While it can be concluded that fluorination
      has some influence on the behaviour of these dimeric PSPs, the influence on the
      selectivity is not as dramatic as in LPFOS. This can be explained by the inferred
      poor hydration of the fluorinated spacer and the positioning of the fluorine
      substituents, too distant from the surfactant head groups to fully exert the
      strong inductive effect required to significantly influence the head group
      chemistry.

PMID- 18639245
TI  - Simulating RNA folding kinetics on approximated energy landscapes.
AB  - We present a general computational approach to simulate RNA folding kinetics that
      can be used to extract population kinetics, folding rates and the formation of
      particular substructures that might be intermediates in the folding process.
      Simulating RNA folding kinetics can provide unique insight into RNA whose
      functions are dictated by folding kinetics and not always by nucleotide sequence
      or the structure of the lowest free-energy state. The method first builds an
      approximate map (or model) of the folding energy landscape from which the
      population kinetics are analyzed by solving the master equation on the map. We
      present results obtained using an analysis technique, map-based Monte Carlo
      simulation, which stochastically extracts folding pathways from the map. Our
      method compares favorably with other computational methods that begin with a
      comprehensive free-energy landscape, illustrating that the smaller, approximate
      map captures the major features of the complete energy landscape. As a result,
      our method scales to larger RNAs. For example, here we validate kinetics of RNA
      of more than 200 nucleotides. Our method accurately computes the kinetics-based
      functional rates of wild-type and mutant ColE1 RNAII and MS2 phage RNAs showing
      excellent agreement with experiment.

PMID- 18639246
TI  - Heated and humidified CO2 prevents hypothermia, peritoneal injury, and intra
      abdominal adhesions during prolonged laparoscopic insufflations.
AB  - BACKGROUND: Insufflation with standard cold-dry CO(2) during laparoscopic surgery
      has been shown to predispose patients to hypothermia and peritoneal injury. This
      study aimed to compare the effect of prolonged cold-dry CO(2) insufflation with
      heated-humidified CO(2) insufflation (3-5 h) on hypothermia, peritoneal damage,
      and intra-abdominal adhesion formation in a rat model. MATERIALS AND METHODS: A
      total of 160 Wistar rats were randomized to undergo no insufflation or
      insufflation with cold-dry CO(2) (21 degrees C, <1% relative humidity) or heated
      humidified CO(2) (37 degrees C, 95% relative humidity) for 3, 4, or 5 h. Core
      body temperature was measured via rectum before and during insufflations.
      Peritoneal samples were taken at 6, 24, 48, and 96 h after treatments and
      analyzed with light microscopy and scanning electron microscopy. Intra-abdominal
      adhesions were evaluated 2 weeks later. RESULTS: Core body temperature
      significantly decreased in the cold-dry group, whereas it was maintained and
      increased in the heated-humidified group. Scanning electron microscopy and light
      microscopy studies showed intense peritoneal injury in the cold-dry CO(2) group
      but significantly less damages in the heated-humidified group. Increased intra
      abdominal adhesion formation was observed in the cold-dry CO(2) group, while no
      adhesions were found in the rats insufflated with heated-humidified CO(2).
      CONCLUSIONS: Heated-humidified CO(2) insufflation results in significantly less
      hypothermia, less peritoneal damage, and decreased adhesion formation as compared
      with cold-dry CO(2) insufflation. Heated-humidified CO(2) may be more suitable
      for insufflation application in prolonged laparoscopic surgery.

PMID- 18639247
TI  - Thiazolidinediones downregulate Wnt/beta-catenin signaling via multiple
      mechanisms in breast cancer cells.
AB  - BACKGROUND: Thiazolidinediones (TZDs) have been demonstrated to possess antitumor
      effects in breast cancer cells, although the mechanisms are not well established.
      We sought to better define TZDs' antitumor effects and molecular mechanisms to
      permit rational utilization of these agents. MATERIALS AND METHODS: We studied
      the effects of TZDs on DNA synthesis (BrdU enzyme-linked immunosorbent assay),
      gene expression (microarray, quantitative reverse transcription-polymerase chain
      reaction, and immunoblot), serine phosphorylation and localization of beta
      catenin (nuclear/cytoplasmic fractionation and immunoblot), transactivation
      activity of beta-catenin/T cell factor 4 (TCF4) (luciferase assay with wild-type
      and mutant TCF4 responsive element), and beta-catenin/TCF4 complex
      (immunoprecipitation) in human breast cancer cells MDA-MB-231 and T47D. RESULTS:
      Troglitazone (TG) down-regulated DNA synthesis in MDA-MB-231 and T47D and
      decreased mRNA expression of the Wnt co-receptors frizzled-1 and low-density
      lipoprotein-related protein 6 (LRP6) as well as protein level of LRP6. TG also
      targets downstream Wnt signaling molecules in T47D cells. TG down-regulates p
      beta-catenin (S33/S37/T41) and promotes translocation of beta-catenin into the
      nucleus. However, TG inhibits beta-catenin-mediated transactivation by down
      regulating TCF4 protein levels, thereby inhibiting beta-catenin/TCF4 complex
      formation. Finally, we found that inhibition of Akt augments TG-mediated down
      regulation of DNA synthesis and this result was accompanied with the decreased
      protein levels of Wnt signaling molecules: LRP6, beta-catenin, and TCF4.
      CONCLUSION: These results suggest that the Wnt/beta-catenin signaling pathway,
      which plays an important role in breast cancer pathogenesis, may be a target for
      TZD treatment. Moreover, a combination of TZDs and a specific Akt inhibitor may
      serve as a new approach to target Wnt/beta-catenin directly and via PI3K/Akt
      action on glycogen synthase-3beta.

PMID- 18639248
TI  - The role of the tumor microenvironment in the progression of pancreatic cancer.
AB  - Pancreatic cancer is the most lethal abdominal malignancy due to its aggressive
      growth and rapid development of distant metastases, thus making treatment
      extremely difficult. Additionally, pancreatic adenocarcinoma is locally invasive,
      surrounded by a dense desmoplastic reaction which can involve adjacent vital
      structures, limiting the number of patients who are candidates for surgical
      resection at the time of diagnosis. Recently the tumor microenvironment in other
      adenocarcinomas has been determined to be an important mediator of cancer cell
      behavior; however, few studies have elucidated the tumor-stroma interactions in
      pancreatic cancer. This review summarizes the role of pancreatic stellate cells,
      perineural invasion, angiogenesis, and inflammatory cells in fostering pancreatic
      cancer cell growth and invasion. The importance of extracellular matrix proteins,
      growth factors, and cytokines is also presented. Finally we suggest ideas for new
      avenues of research into the pancreatic tumor microenvironment which may permit
      the development of novel, more effective treatments for pancreatic cancer.

PMID- 18639249
TI  - Mixed endothelin receptor antagonism with tezosentan improves intestinal
      microcirculation in endotoxemic shock.
AB  - BACKGROUND: Microcirculatory dysfunction is a common feature of sepsis. The
      potent vasoconstrictor endothelin (ET) is released in sepsis and endotoxemia,
      potentially contributing to sepsis-induced microcirculatory failure. In this
      study we tested the hypothesis that mixed ET receptor antagonism with tezosentan
      would improve splanchnic microcirculatory blood flow in acute porcine
      endotoxemia. MATERIALS AND METHODS: Sixteen anesthetized and mechanically
      ventilated pigs received an infusion of endotoxin for 300 min. After 120 min
      eight pigs received a bolus dose of tezosentan 1 mg/kg followed by an infusion of
      tezosentan of 1 mg/kg/h throughout the experiment. Eight pigs served as endotoxin
      controls. Laser Doppler flowmetry was used to measure microcirculatory blood flow
      in the liver and in the ileal and colon mucosa. PCO(2) in the ileal mucosa was
      measured by air tonometry and portal vein flow by an ultrasonic flow probe.
      RESULTS: Endotoxin administration induced a state of shock with impaired
      splanchnic microcirculatory blood flow. Microcirculation in the mucosa of the
      colon and ileum and mucosal-arterial PCO(2) gap were improved by tezosentan.
      Portal vein flow was increased, but hepatic microcirculatory blood flow was not
      significantly improved. Tezosentan preserved cardiac index and decreased
      pulmonary capillary wedge pressure compared to controls, without causing any
      differences in the heart rate or mean arterial blood pressure response.
      Tezosentan also distinctly improved pH and arterial lactate values. CONCLUSIONS:
      The findings of this study indicate that ET is involved in the microcirculatory
      dysfunction seen in the ileal and colon mucosa in early endotoxemia. Moreover,
      this detrimental effect was counteracted by i.v. administration of the mixed ET
      receptor antagonist tezosentan.

PMID- 18639250
TI  - Gene expression during liver regeneration after partial hepatectomy in mice
      lacking type 1 tumor necrosis factor receptor.
AB  - BACKGROUND: To investigate the function of tumor necrosis factor-alpha (TNF
      alpha) during hepatocyte proliferation, we studied liver regeneration following
      partial hepatectomy in mice lacking type 1 TNF receptor (TNFR-1). MATERIALS AND
      METHODS: TNFR-1 knockout (KO) and wild-type mice were subjected to partial (two
      thirds) hepatectomy. Liver regeneration was evaluated by assessing liver weights
      and Ki67 immunohistochemistry. Riken complementary DNA microarray analysis was
      performed for liver samples from mice undergoing partial hepatectomy to better
      compare different mouse partial hepatectomy models (TNFR-1 KO mice, KO group; and
      wild-type mice, W group). RESULTS: Liver weight was regained after 14 days in the
      KO group, and after 7 days in the W group. Genes including lipopolysaccharide,
      toll-like receptor 4 precursor, mitogen-activated protein kinase kinase kinase 4,
      mitogen-activated protein kinase kinase kinase kinase 4, and mitogen-activated
      protein kinase 8-interacting protein were up-regulated in the KO group. As for
      the cell-cycle-regulated genes, the levels of cyclin D1, nuclear factor-kappa B
      light chain, and TNF receptor super family membrane 1a were down-regulated in the
      KO group. Microarray analysis showed decreased activities of the hexokinase- and
      phospho-fructokinase-related glycolytic pathways in the KO group. CONCLUSIONS:
      These results contribute to the better understanding of the mechanisms of liver
      regeneration after partial hepatectomy in TNFR-1 KO mice.

PMID- 18639251
TI  - Tumour glycolysis: the many faces of HIF.
AB  - We present a model for tumour metabolism that incorporates both
      microenvironmental (extracellular) and oncogenic (intracellular) influences. We
      explore the effects of the interaction between the hypoxic microenvironment and
      intracellular signalling on the glycolytic response of tumour tissue, finding
      that the glycolytic state is dependent on a delicately balanced interplay between
      the cellular hypoxic response, mediated by hypoxia-inducible factor-1alpha (HIF
      1alpha), and growth-factor signalling cascades, which are frequently mutated in
      cancers. Our findings demonstrate the importance of considering both
      environmental and intracellular regulation when interpreting tumour metabolism
      for diagnostic or prognostic purposes. To illustrate this, we demonstrate the
      potential impact of this multi-factorial regulation on the kinetics of
      radiolabelled glucose analogues, used in positron emission tomography (PET).

PMID- 18639263
TI  - Outcomes following sling surgery: importance of definition of success.
AB  - PURPOSE: The assessment of incontinence therapies is complicated by the diverse
      outcomes instruments and definitions of success used by investigators. We defined
      this effect by using varied definitions of success to perform outcomes analysis
      following sling placement. MATERIALS AND METHODS: A retrospective review of
      patients undergoing SPARC (314) and autologous rectus pubovaginal sling (127)
      placement was performed, with 204 patients with the SPARC and 67 with pubovaginal
      sling completing questionnaire surveillance with the minimum 12-month followup.
      Outcomes were assessed using a questionnaire comprising validated incontinence
      questionnaires (Urogenital Distress Inventory and Incontinence Impact
      Questionnaire) and additional items addressing satisfaction. Success rates were
      compared using alternate definitions of success across all outcomes measures (eg
      dry rate, pad rate, percent improvement, degree of satisfaction). RESULTS: Wide
      variations in outcomes were seen depending on the definition used for success
      (SPARC success range 33% to 87%, pubovaginal sling 40% to 79%). Total absence of
      leakage was the strictest definition of success while continued use of 1 to 3
      liners was associated with the highest success rates. In addition, 74% of
      patients with SPARC placement and 66% with the pubovaginal sling reported
      willingness to undergo sling surgery again despite the treatment failing to meet
      the criteria for success under multiple definitions. Finally, the individual
      sling type (SPARC vs pubovaginal) associated with the superior success rate
      varied with the definition of success. However, these differences failed to
      achieve statistical significance. CONCLUSIONS: Our data suggest that success
      rates following sling placement are significantly affected by the definition of
      success. Investigation to define standardized outcomes measures following
      incontinence surgery is of great importance to the urological community.

PMID- 18639264
TI  - Incidence and remission of lower urinary tract symptoms during 12 years after the
      first delivery: a cohort study.
AB  - PURPOSE: We estimated the incidence and remission of lower urinary tract symptoms
      during the 12 years following the first pregnancy and delivery. MATERIALS AND
      METHODS: In a cohort study 242 primiparae were questioned about lower urinary
      tract symptoms 3 months, 5 years and 12 years after the first delivery. RESULTS:
      From 3 months to 5 years after first delivery the incidence of stress urinary
      incontinence, urge urinary incontinence, urgency, diurnal frequency and nocturia
      was 56 of 213 cases (26.3%), 33 of 219 (15.1%), 33 of 206 (16.0%), 49 of 219
      (22.4%) and 6 of 225 (2.7%), respectively. Remission of stress urinary
      incontinence, urge urinary incontinence, urgency, diurnal frequency and nocturia
      during the same period occurred in 1 of 11 cases (9.1%), 2 of 5 (40%), 2 of 5
      (40%), 4 of 7 (57.1%) and 1 of 1 (100%), respectively. From 5 to 12 years after
      the first delivery the incidence of stress urinary incontinence, urge urinary
      incontinence, urgency, diurnal frequency and nocturia was 40 of 158 cases
      (25.3%), 25 of 188 (13.3%), 24 of 175 (13.7%), 40 of 174 (23.0%) and 13 of 220
      (5.9%), respectively. Remission of stress urinary incontinence, urge urinary
      incontinence, urgency, diurnal frequency and nocturia during the same period
      occurred in 14 of 66 cases (21.2%), 13 of 36 (36.1%), 22 of 36 (61.1%), 14 of 52
      (26.9%) and 4 of 6 (66.7%), respectively. Of 62 women with pure stress urinary
      incontinence during the first pregnancy and puerperium 20 (32.2%) had pure stress
      urinary incontinence, 3 (4.8%) had pure urge urinary incontinence and 15 (24.2%)
      had mixed urinary incontinence 12 years later. Of 13 women with pure urge urinary
      incontinence during the first pregnancy and puerperium 3 (23.1%) had pure urge
      urinary incontinence, 2 (15.4%) had pure stress urinary incontinence and 3
      (23.1%) had mixed urinary incontinence 12 years later. The overall prevalence of
      lower urinary tract symptoms 12 years after the first delivery increased
      significantly. CONCLUSIONS: The incidence and remission of lower urinary tract
      symptoms after the first pregnancy and delivery fluctuate and the types of
      urinary incontinence may interchange, while the overall prevalence of lower
      urinary tract symptoms increases in the long term.

PMID- 18639265
TI  - The presacral space and its impact on sacral neuromodulator implantation.
AB  - PURPOSE: We describe the presacral space and its potential impact on sacral
      neuromodulator implantation and bowel injury. MATERIALS AND METHODS: Parasagittal
      images containing bilateral sacral foramina (S2-S4) were examined on 45 pelvic
      magnetic resonance images. Images were excluded from analysis if they were poor
      quality or had any history causing distortion of normal anatomy. We measured the
      natural angle between the foramina and the dorsal skin to approximate the needle
      angulation during neuromodulator electrode placement. Using these angles we
      measured the distance from the skin to any bowel (D1), the skin to the dorsal
      sacrum (D2) and then calculated the distance from the dorsal sacrum to any bowel
      (D3). RESULTS: Mean subject age was 45 years (range 19 to 78) and body mass index
      was 27.9 kg/m(2) (range 18.6 to 56.2). At S3 the mean foraminal angle and D3 were
      46 +/- 8.4 degrees and 27.4 +/- 11.7 mm, respectively. Increasing age was
      moderately correlated to widening D3 at each foramina (r = 0.3, Pearson's p
      <0.05). Body mass index did not consistently vary with D3 at any foramina.
      CONCLUSIONS: Our measurements suggest that the presacral space can be expected to
      be approximately 27 mm at the level of S3 where the neuromodulator electrode is
      implanted. It is possible to encounter bowel while performing this implantation
      using standard techniques and equipment. We recommend the standard use of
      fluoroscopy during placement.

PMID- 18639266
TI  - Robotic reconstruction for recurrent supratrigonal vesicovaginal fistulas.
AB  - PURPOSE: We report our experience with robotic reconstruction for recurrent
      supratrigonal vesicovaginal fistulas and its outcome. MATERIALS AND METHODS: From
      August 2006 to October 2007 we treated 7 cases of recurrent supratrigonal
      vesicovaginal fistula. Salient features of our technique are 1) vaginoscopy and
      cystoscopy with bilateral Double-J stent or ureteral catheter placement and
      placement of a catheter through the fistula from vagina to bladder, 2) patient
      positioning in a low lithotomy position with a 60-degree Trendelenburg tilt and a
      5-port transperitoneal approach, 3) peritoneoscopy and adhesiolysis with minimal
      posterior cystotomy encircling the fistulous opening, 4) mobilization of the
      bladder and vaginal flaps to allow tension-free closure, 5) excision of the
      fistulous rim, 6) bladder and vaginal edge freshening, 7) bladder and vaginal
      closure, 8) omental, peritoneal or sigmoid epiploic tissue interposition and 9)
      insertion of a Foley catheter and drain. Difficulty was primarily noted with
      regard to the safe establishment of pneumoperitoneum, the need for extensive
      adhesiolysis, dissection of the fistula from perifistulous fibrosis in close
      vicinity to the ureteral opening, tension-free closure of the larger defect and
      occasional absence of omentum for use as interposition tissue. RESULTS: The
      average size of supratrigonal fistulas was 3.0 cm. Mean operative time was 141
      minutes (range 110 to 160). Mean blood loss was 90 cc. No significant
      intraoperative or postoperative complications were observed. Mean hospital stay
      was 3 days. The catheter was removed 14 days postoperatively. All patients had a
      successful outcome. CONCLUSIONS: Our experience suggests that robotic repair for
      recurrent vesicovaginal fistulas is feasible, results in low morbidity and
      provides outstanding results. It provides an attractive option for vesicovaginal
      fistula repair by a minimally invasive approach for the surgeon and the patient
      alike.

PMID- 18639267
TI  - Urinary stone disease in adults with celiac disease: prevalence, incidence and
      urinary determinants.
AB  - PURPOSE: Intestinal diseases may cause urinary stone disease via hyperoxaluria or
      diarrhea induced hyperconcentrated acidic urine. Data are missing on urinary
      stone disease in celiac disease, a common malabsorptive disorder. In this study
      we analyzed urinary stone disease and urine composition in adults with celiac
      disease. MATERIALS AND METHODS: Study patients were 18 years or older, untreated,
      and newly diagnosed with celiac disease by serum markers and jejunal biopsy.
      Clinical presentation of celiac disease was assessed focusing on 5 disorders of
      diarrhea, and deficiency of calorie (low body mass index or weight loss), lipid
      (low prothrombin time or low serum lipids), iron (low hemoglobin or low serum
      ferritin) and calcium (low serum calcium or low bone densitometry). Urinary stone
      disease history was assessed by questionnaire (imaging, stone excretion, stone
      disruption/removal). Urinary variables were measured in a 24-hour collection in a
      subgroup of patients. RESULTS: Under untreated conditions (baseline) urinary
      stone disease was independent of celiac disease presentation and more prevalent
      in patients with celiac disease than in a population sample used as a control
      (608 and 3,540, 7.9% and 5.0%, sex and age adjusted odds ratio 4.0, 95% CI 2.7
      5.9). Excluding from analysis individuals with baseline urinary stone disease,
      the incidence of urinary stone disease history was not significantly different
      between the treated celiac disease (gluten-free diet) and control population (458
      and 3,003, 2.4% vs 3.9%). The urine of untreated patients with celiac disease
      differed from that of healthy volunteers with 120% higher oxalate and 43% lower
      calcium (in 45 and 45, p <0.001). A gluten-free diet corrected urinary
      abnormalities (p <0.01). CONCLUSIONS: Urinary stone disease risk is high in
      untreated patients with celiac disease independent of overt malabsorption.
      Hyperoxaluria is likely the underlying disorder. A gluten-free diet reduces
      urinary stone disease risk and oxaluria.

PMID- 18639268
TI  - A randomized clinical trial of lidocaine jelly for prevention of inadvertent
      retrograde stone migration during pneumatic lithotripsy of ureteral stone.
AB  - PURPOSE: We studied the efficacy of lidocaine jelly instillation proximal to the
      ureteral stone during intracorporeal lithotripsy using a semirigid ureteroscope
      for the prevention of retrograde migration and improvement in stone-free rate.
      MATERIALS AND METHODS: From November 2006 to September 2007, 50 patients with 5
      to 18 mm ureteral stones undergoing ureteroscopic removal using pneumatic
      lithotripsy were randomized into 2 groups. Group 1 (25 patients) had lidocaine
      jelly instilled proximal to the stone before and after fragmentation, and group 2
      was the control group (25 patients). Ureteroscopy was performed using an 8 or
      6.4Fr semirigid ureteroscope. A 5Fr ureteral stent was advanced beyond the stone.
      Lidocaine jelly (2 ml) was instilled and lithotripsy was performed with a Swiss
      LithoClast . A 5Fr ureteral catheter was left in place for 24 hours. Patients
      were followed at 24 hours with plain x-ray of the kidneys, ureters and bladder,
      and at 2 weeks with noncontrast enhanced computerized tomography of the kidneys,
      ureters and bladder. RESULTS: The 2 groups were comparable with regard to age and
      stone size. Stone or stone fragment migration occurred in 4% and 28% of patients
      in groups 1 and 2, respectively, and this difference was statistically
      significant (p = 0.002). At 2 weeks followup with imaging the stone-free rate was
      96% and 72% in groups 1 and 2, respectively, and this difference was also
      statistically significant (p = 0.045). Although the mean operative time was
      slightly longer in the treatment group (33.56 +/- 13 vs 35.84 +/- 12.5 minutes)
      the difference was not significant (p = 0.450). CONCLUSIONS: Lidocaine jelly
      instillation proximal to ureteral calculi during lithotripsy is an effective
      method of preventing retrograde stone displacement as well as significantly
      improving the stone-free rate.

PMID- 18639269
TI  - Role of ureteral stenting after uncomplicated ureteroscopy for distal ureteral
      stones: a randomized, controlled trial.
AB  - PURPOSE: We determined the differences in outcome between ureteral stenting and
      nonstenting following uncomplicated ureteroscopy for distal ureteral stones.
      MATERIALS AND METHODS: A total of 220 patients treated with successful
      ureteroscopy for distal ureteral stones were randomized to 2 equal groups
      according to postoperative placement of a ureteral stent (Cook Ireland, National
      Technological Park, Ireland), including group 1--without a stent and group 2-
      with a stent. Outcome measures were flank pain and dysuria at 48 hours and 1
      week, early postoperative complications, analgesia need, rehospitalization,
      return to normal physical activity, stone-free rate, stone recurrence and late
      postoperative complications. Patients were followed a mean +/- SD of 25 +/- 9
      months (range 12 to 49). RESULTS: Early postoperative complications, including
      low grade fever, hematuria and urinary tract infection, were observed in 22
      patients (20%) in group 1 and 19 (19%) in group 2, a difference of no significant
      value. Mean initial hospitalization and time to return to normal physical
      activity were not different between the 2 groups. At 48 hours and 1 week there
      was no significant difference in flank pain between the 2 groups, while dysuria
      was significantly less in the nonstented group. The amount of analgesics required
      in the recovery room was not different but after discharge from the hospital
      stented patients used a larger amount of analgesia while the stent was still in
      the ureter. The stone-free rate at 4 weeks was 100% in each group. Late
      postoperative sequelae, including stone recurrence and ureteral narrowing, were
      reported in 6 patients (5.5%) in group 1 and 4 (3.6%) in group 2, a difference of
      no significant value. CONCLUSIONS: Uncomplicated ureteroscopy for treatment of
      distal ureteral stones is safe without stent placement. Patients without stents
      have significantly fewer irritative bladder symptoms and are not at risk of
      increased complications.

PMID- 18639270
TI  - Decreased stone-free rates after percutaneous nephrolithotomy for high calcium
      phosphate composition kidney stones.
AB  - PURPOSE: To our knowledge the most effective treatment in patients with renal
      stones containing calcium phosphate remains unknown. An inverse correlation
      exists between calcium phosphate stone composition and the stone-free rate of
      shock wave lithotripsy. It is unknown whether this is due to treatment type
      (shock wave lithotripsy) or to a feature unique to calcium phosphate stones. We
      determined whether calcium phosphate stone composition affects the stone-free
      rate of percutaneous nephrolithotomy. MATERIALS AND METHODS: Percutaneous
      nephrolithotomy was performed in 111 patients between 2001 and 2006 and stone
      fragments were analyzed for calcium phosphate composition. Patients were
      categorized into groups based on calcium phosphate content. All patients
      underwent preoperative computerized tomography. Patients were considered stone
      free after percutaneous nephrolithotomy when fragments were 2 mm or less on
      noncontrast computerized tomography. RESULTS: A total of 213 percutaneous
      nephrolithotomies were performed. An increased percent of calcium phosphate was
      related to a decreased percutaneous nephrolithotomy success rate (p = 0.005),
      independent of preoperative stone burden (p = 0.8). Patients with greater than
      60% calcium phosphate stones were significantly less likely to be stone-free
      after percutaneous nephrolithotomy than those with less calcium phosphate (60%,
      OR 2.45, 95% CI 1.103-5.4401 vs 80%, OR 3.72, 95% CI 1.33-10.44). CONCLUSIONS:
      High calcium phosphate renal stone content leads to a decreased stone-free rate.
      Further study is required to determine the mechanism of stone resilience as well
      as the most appropriate treatment modality in patients with high calcium
      phosphate composition kidney stones.

PMID- 18639271
TI  - Microsurgical denervation of the spermatic cord for chronic orchialgia: long-term
      results from a single center.
AB  - PURPOSE: We assessed the long-term efficacy, complications and patient
      perceptions of microsurgical denervation of the spermatic cord in the treatment
      of chronic orchialgia. MATERIALS AND METHODS: Microsurgical denervation of the
      spermatic cord was performed on 95 testicular units in 79 men (mean age 40.3
      years, mean duration of pain 62 months, 16 bilateral) for chronic orchialgia.
      Conservative management failed in all, and patients were evaluated with an
      extensive medical history and physical examination. To be a candidate for
      microsurgical denervation of the spermatic cord each man would have responded
      either completely or partially to spermatic cord block (greater than 50% decrease
      in pain) and had no identifiable reversible etiology. Postoperative pain rating
      scales (0 to 10) were used to determine efficacy. RESULTS: Mean followup was 20.3
      months (range 1 to 102 months) and complete, durable relief was noted in 67 (71%)
      testicular units, partial relief in 17 (17%), and unchanged in 11 (12%). No
      patients reported worse pain. Complications included testicular atrophy without
      hypogonadism in 2 patients, superficial wound infection in 2, hydrocele in 2 and
      an incisional hematoma in 1. CONCLUSIONS: Microsurgical denervation of the
      spermatic cord is a minimally invasive, effective and durable management option
      for treatment of chronic orchialgia refractory to medical management, preserving
      the physiological function and psychological role of the testes.

PMID- 18639275
TI  - Re: Prognostic value of MET, RON and histoprognostic factors for urothelial
      carcinoma in the upper urinary tract. E. Comperat, M. Roupret, E. Chartier
      Kastler, M. O. Bitker, F. Richard, P. Camparo, F. Capron and O. Cussenot. J Urol
      2008; 179: 868-872.

PMID- 18639276
TI  - Influence of temperature on pudendal nerve block induced by high frequency
      biphasic electrical current.
AB  - PURPOSE: We determined the influence of temperature on the minimal stimulation
      frequency required to block pudendal nerve conduction. MATERIALS AND METHODS: The
      pudendal nerve block induced by high frequency, biphasic electrical current was
      investigated at different temperatures using cats under alpha-chloralose
      anesthesia. Urethral pressure was measured to indicate pudendal nerve activation
      or block. RESULTS: As stimulation frequency was increased above a frequency
      threshold, the urethral pressure response was decreased and the pudendal nerve
      was blocked. The minimal stimulation frequency required to block the pudendal
      nerve was decreased from 6 to 4 kHz as the temperature was decreased from 37C to
      15C. At a 4 kHz frequency the maximal temperature below which the pudendal nerve
      could be blocked was 24.5C. CONCLUSIONS: To block pudendal nerve conduction at
      body temperature (37C) the stimulation frequency must be greater than 6 kHz. This
      study provides a practical guide for blocking the pudendal nerves to restore
      efficient voiding after spinal cord injury.

PMID- 18639277
TI  - Activation of somatosensory afferents elicit changes in vaginal blood flow and
      the urethrogenital reflex via autonomic efferents.
AB  - PURPOSE: We examined the effects of pudendal sensory nerve stimulation and
      urethral distention on vaginal blood flow and the urethrogenital reflex, and the
      relationship between somatic and autonomic pathways regulating sexual responses.
      MATERIALS AND METHODS: Distention of the urethra and stimulation of the pudendal
      sensory nerve were used to evoke changes in vaginal blood flow (laser Doppler
      perfusion monitoring) and pudendal motor nerve activity in anesthetized, spinally
      transected female rats. Bilateral cuts of either the pelvic or hypogastric nerve
      or both autonomic nerves were made, and blood flow and pudendal nerve responses
      were reexamined. RESULTS: Stimulation of the pudendal sensory nerve or urethral
      distention elicited consistent increases in vaginal blood flow and rhythmic
      firing of the pudendal motor nerve. Bilateral cuts of the pelvic plus hypogastric
      nerves significantly reduced vaginal blood flow responses without altering
      pudendal motor nerve responses. Pelvic nerve cuts also significantly reduced
      vaginal blood flow responses. In contrast, hypogastric nerve cuts did not
      significantly change vaginal blood flow. Bilateral cuts of the pudendal sensory
      nerve blocked pudendal motor nerve responses but stimulation of the central end
      evoked vaginal blood flow and pudendal motor nerve responses. CONCLUSIONS:
      Stimulation of the sensory branch of the pudendal nerve elicits vasodilatation of
      the vagina. The likely mechanism is via activation of spinal pathways that in
      turn activate pelvic nerve efferents to produced changes in vaginal blood flow.
      Climatic-like responses (firing of the pudendal motor nerve) occur in response to
      stimulation of the pudendal sensory nerve and do not require intact pelvic or
      hypogastric nerves.

PMID- 18639278
TI  - Investigation of a novel degradable ureteral stent in a porcine model.
AB  - PURPOSE: Ureteral stents often result in patient morbidity and the potential for
      a forgotten stent. When the suture tether is detached, a secondary procedure is
      required for removal. Previous attempts at developing biodegradable ureteral
      stents have been unsuccessful since those stents were not biocompatible or they
      failed to degrade in timely fashion. We evaluated a new biodegradable Double-J
      stent in a porcine model. MATERIALS AND METHODS: A total of 36 Yorkshire pigs
      were stented unilaterally with a biodegradable Uriprene stent or a standard
      biostable control stent. Excretory urograms, and blood and urine tests were
      performed at weeks 2, 3, 4, 5, 7 and 10. Four animals per group were sacrificed
      after 2, 4, 7 and 10 weeks to determine stent degradation and obtain samples for
      pathological evaluation. RESULTS: Degradable ureteral stents began to degrade at
      3 weeks. By weeks 7 and 10, 60% and 100% of the stents, respectively, were fully
      degraded. There was no significant difference in laboratory parameters or the
      amount of hydronephrosis between the 2 groups. However, ureteral dilatation was
      significantly more pronounced in the control group than in the Uriprene group.
      The novel stent was biocompatible on histological evaluation and it led to
      significantly less urinary tract infections than in controls. CONCLUSIONS: The
      novel Uriprene stents provided drainage similar to that of regular stents and
      they were completely degraded by 10 weeks. Moreover, these stents resulted in
      less ureteral dilatation and fewer positive urine cultures. Biocompatibility was
      good and human trials will be forthcoming.

PMID- 18639279
TI  - Histopathological assessment of prostate cancer bone osteoblastic metastases.
AB  - PURPOSE: Many patients with prostate cancer have bone metastases that appear
      osteoblastic on radiography, and yet these patients are at increased risk for
      fracture. The discrepancy between the radiological and clinical aspects of those
      events is not well understood. We better characterized the histopathology of bone
      processes in prostate cancer bone metastases. MATERIALS AND METHODS:
      Histomorphometry was used to evaluate multisite bone biopsies in 12 patients who
      died with multiple bone metastases, of whom 7 had received bisphosphonate
      therapy. RESULTS: Bone histomorphometry revealed a wide spectrum of cancer
      induced bone changes in different metastatic sites in individual patients,
      ranging from a pronounced osteodense to a pronounced osteopenic type. Each
      metastatic lesion was associated with various amounts of resorption. Decreased
      bone volume was seen in half of all biopsies. Osteodense lesions were largely
      composed of under mineralized woven bone, which increases the frailty of new
      bone. Interestingly woven bone was produced by alkaline phosphatase spindle
      shaped cells arising from the connective stroma surrounding tumor cells. The bone
      response generally was similar in bisphosphonate treated patients and those who
      did not receive bisphosphonate. CONCLUSIONS: Despite the osteoblastic nature of
      bone metastases in prostate cancer, the osteolytic-osteopenic bone lesions found
      in each clinically osteoblastic case may explain the frequent fractures observed
      in these cases. In addition, the finding that woven bone formed directly from the
      tumor stroma and not from the adjacent bone surface supports further research
      into the mechanisms of abnormal bone formation in prostate cancer bone
      metastases.

PMID- 18639280
TI  - Is vascular endothelial growth factor modulation a predictor of the therapeutic
      efficacy of gefitinib for bladder cancer?
AB  - PURPOSE: The epidermal growth factor receptor inhibitor gefitinib (Iressa) is
      currently being studied in patients with bladder cancer and it has significant
      anti-angiogenic activity. We investigated the relationship between the modulation
      of vascular endothelial growth factor (Santa Cruz Biotechnology, Santa Cruz,
      California) expression and the biological efficacy of gefitinib for bladder
      cancer. MATERIALS AND METHODS: In vitro the 4 bladder cancer cell lines 253JB-V,
      UMUC-3, KU-7 and UMUC-13 were treated with gefitinib and vascular endothelial
      growth factor secretion was measured. The effects of gefitinib on vascular
      endothelial growth factor promoter, proliferation, cell cycle and downstream
      signals were evaluated. In vivo 253JB-V and UMUC-13 were injected into nude mice
      and tumors were treated with 2 mg gefitinib per day. Tumor kinetics were
      determined and the levels of phospho-epidermal growth factor receptor
      (Biosource), vascular endothelial growth factor, phospho-vascular endothelial
      growth factor (Cell Signaling Technology), angiogenesis and apoptosis were
      measured. RESULTS: Epidermal growth factor receptor (Neomarkers, Fremont,
      California) phosphorylation was blocked efficiently in all cell lines at
      concentrations of 0.5 microM or greater. Gefitinib (1 microM) induced an
      accumulation of cells in G0/G1 without apoptosis in 253J B-V cells, whereas it
      had no effect in other cell lines. Gefitinib inhibited vascular endothelial
      growth factor secretion in 253JB-V and UMUC-13 (concentration inhibiting a 50%
      response 0.5 and 0.1 microM, respectively) but not in UMUC-3 or KU-7. Gefitinib
      decreased vascular endothelial growth factor promoter activity in 253JB-V and
      UMUC-13 by 40% to 60%. In vivo the growth of 253JB-V tumors was significantly
      inhibited by gefitinib, whereas no effect was demonstrated in UMUC-13 tumors.
      Vascular endothelial growth factor expression and vascular endothelial growth
      factor receptor activation were significantly decreased in 253JB-V tumors and to
      a greater extent in resistant UMUC-13 tumors. Gefitinib inhibited angiogenesis
      and induced apoptosis in sensitive 253JB-V tumors only. CONCLUSIONS: Epidermal
      growth factor receptor blockade exerts an anti-angiogenic effect on bladder
      cancer cells, in part by modulating vascular endothelial growth factor
      expression. However, down-regulation of vascular endothelial growth factor
      expression is not sufficient to inhibit bladder cancer growth and it should not
      be used as a predictor of the therapeutic efficacy of gefitinib.

PMID- 18639281
TI  - Methylation of the RUNX3 promoter as a potential prognostic marker for bladder
      tumor.
AB  - PURPOSE: DNA methylation is a key regulator of gene transcription and genomic
      stability, and alterations in DNA methylation patterns are frequently detected in
      human tumors. Previously we reported that inactivation of RUNX3 by primarily
      epigenetic alterations in DNA methylation is closely associated with bladder
      tumor development, recurrence and progression. In the current series we evaluated
      the association between RUNX3 inactivation and bladder tumors after a long-term
      followup study. MATERIALS AND METHODS: We used previously published data on the
      methylation patterns of RUNX3 in bladder tumor samples as well as 25 new data
      sets obtained by methylation specific polymerase chain reaction and direct DNA
      sequencing. Of the 149 patients examined 118 were followed periodically and
      included in the final analysis. Median followup was 49.8 months (range 1 to 146).
      RESULTS: RUNX3 promoter methylation was observed in 84 of the 118 tumor samples
      (71.2%) examined. RUNX3 methylation patterns correlated significantly with the
      development of invasive tumor, tumor progression, and overall and cancer specific
      survival (each p <0.05). Kaplan-Meyer curves showed identical results (p <0.05).
      Multivariate Cox regression models revealed that RUNX3 methylation status was a
      strong predictor of tumor progression and cancer specific survival. CONCLUSIONS:
      Results strongly suggest that inactivation of RUNX3 by the methylation of its
      promoter region is a significant risk factor for invasive bladder tumors, tumor
      progression and cancer specific survival. RUNX3 promoter methylation status could
      be a promising marker for assessing the prognosis of human bladder tumors.

PMID- 18639282
TI  - Fatty acid synthase over expression is an indicator of tumor aggressiveness and
      poor prognosis in renal cell carcinoma.
AB  - PURPOSE: Fatty acid synthase is a key enzyme in the de novo biosynthesis of fatty
      acids. Increased fatty acid synthase expression and its association with tumor
      aggressiveness and poor prognosis have been demonstrated in various human
      malignant tumors. We investigated fatty acid synthase expression in patients with
      renal cell carcinoma and its impact on clinicopathological parameters. MATERIALS
      AND METHODS: Fatty acid synthase expression in 120 patients with renal cancer was
      examined by immunohistochemistry. The relationship between fatty acid synthase
      expression status and various clinicopathological parameters was analyzed.
      Survival analysis was performed using the log rank test and a Cox multivariate
      hazard model. RESULTS: Of 120 tumors 18 (15%) showed positive fatty acid synthase
      expression, which was significantly associated with advanced pathological T stage
      (pT3-4, p = 0.0009), regional lymph node metastasis (p = 0.0429), distant
      metastasis (p = 0.0042), higher histological grade (G3, p = 0.0017) and
      microvascular invasion (p = 0.0357). Patients with positive fatty acid synthase
      expression had significantly shorter cancer specific survival than those with
      negative FAS expression (p <0.0001). Multivariate Cox proportional hazards model
      analysis demonstrated that positive fatty acid synthase expression was an
      independent predictor of shortened cancer specific survival (p = 0.0363, HR
      3.736). CONCLUSIONS: Increased FAS expression could be an indicator of tumor
      aggressiveness and poor prognosis of renal cell carcinoma. Patients with fatty
      acid synthase positive tumors should be followed closely and carefully, and
      adjuvant therapy should be considered.

PMID- 18639283
TI  - Decreased acetylation of histone H3 in renal cell carcinoma: a potential target
      of histone deacetylase inhibitors.
AB  - PURPOSE: Recent studies suggest that alterations in chromatin structure by
      histone acetylation may have an important role in the neoplastic process. We
      evaluated histone H3 acetylation in renal cell carcinoma and the effects of a
      histone deacetylase inhibitor on renal cancer cell lines. MATERIALS AND METHODS:
      The expression of acetylated histone H3 (Lys9) in renal cell carcinoma and
      corresponding nonneoplastic tissue specimens was evaluated. We next assessed
      immunohistologically the relationships between acetylated histone H3 expression
      and clinicopathological parameters in 44 cases of renal cell carcinoma.
      Furthermore, we evaluated the effects of the histone deacetylase inhibitor
      depsipeptide on the renal cancer cell lines Caki-1, ACHN, 769P and 786O (ATCC).
      RESULTS: Acetylated histone H3 expression was decreased in 85.0% of renal cell
      carcinomas compared to levels in nonneoplastic tissue. Decreased expression was
      related to high nuclear tumor grade and advanced pathological tumor stage (p =
      0.048 and 0.032, respectively). Depsipeptide inhibited cell line proliferation in
      a time and dose dependent manner. Depsipeptide induced apoptosis in Caki-1, ACHN
      and 786O, and induced G2 cell cycle arrest in 769P. Concomitantly depsipeptide
      increased acetylated histone H3 and p21(WAF/CIP1) expression, and induced Bcl-2
      phosphorylation. CONCLUSIONS: These results suggest that the decreased
      acetylation of histone H3 is a common alteration in a malignant phenotype of
      renal cell carcinoma. Increasing the amount of acetylated histone H3 might be a
      therapeutic option for renal cell carcinoma.

PMID- 18639285
TI  - Acute gonadal vein thrombosis secondary to terminal ileitis and thrombophilia.

PMID- 18639284
TI  - Identification of novel epigenetic markers for clear cell renal cell carcinoma.
AB  - PURPOSE: We identified significantly hypermethylated genes in clear cell renal
      cell carcinoma. MATERIALS AND METHODS: We previously identified a set of under
      expressed genes in renal cell carcinoma tissue through transcriptional profiling
      and a robust computational screen. We selected 19 of these genes for
      hypermethylation analysis using a rigorous search for the best candidate regions,
      considering CpG islands and transcription factor binding sites. The genes were
      analyzed for hypermethylation in the DNA of 38 matched clear cell renal cell
      carcinoma and normal samples using matrix assisted laser desorption ionization
      time-of-flight mass spectrometry. The significance of hypermethylation was
      assessed using 3 statistical tests. We validated the down-regulation of
      significantly hypermethylated genes at the RNA and protein levels in a separate
      set of patients using reverse transcriptase-polymerase chain reaction,
      immunohistochemistry and Western blots. RESULTS: We found 7 significantly
      hypermethylated regions from 6 down-regulated genes, including SFRP1, which was
      previously shown to be hypermethylated in renal cell carcinoma and other cancer
      types. CONCLUSIONS: To our knowledge we report for the first time that another 5
      genes (SCNN1B, SYT6, DACH1, and the tumor suppressors TFAP2A and MT1G) are
      hypermethylated in renal cell carcinoma. Robust computational screens and the
      high throughput methylation assay resulted in an enriched set of novel genes that
      are epigenetically altered in clear cell renal cell carcinoma. Overall the
      detection of hypermethylation in these highly down-regulated genes suggests that
      assaying for their methylation using cells from urine or blood could provide the
      basis for a viable diagnostic test.

PMID- 18639286
TI  - Adenomatoid tumor of the adrenal gland.

PMID- 18639287
TI  - Differences in testicular development between 5alpha-reductase 2 deficiency and
      isolated bilateral cryptorchidism.
AB  - PURPOSE: We demonstrated that infertility develops in most patients with steroid
      5alpha-reductase 2 deficiency. MATERIALS AND METHODS: We compared the testicular
      histopathology of boys with steroid 5alpha-reductase 2 deficiency to that of boys
      with isolated bilateral cryptorchidism. RESULTS: Testes with steroid 5alpha
      reductase 2 deficiency lacked spermatocytes but had Ad spermatogonia and a normal
      germ cell count. In contrast, bilateral cryptorchid testes had severe germ cell
      depletion and the majority lacked Ad spermatogonia. CONCLUSIONS: In patients with
      steroid 5alpha-reductase 2 deficiency the impaired second step of germ cell
      maturation results in defective transformation of spermatogonia into
      spermatocytes. The position of the undescended testis appears to have no major
      pathological impact on the development of germ cells in patients with steroid
      5alpha-reductase 2 deficiency.

PMID- 18639288
TI  - Transient asynchronous testicular growth in adolescent males with a varicocele.
AB  - PURPOSE: We assessed the testicular growth of adolescent males followed
      nonsurgically for the presence of left varicocele. MATERIALS AND METHODS: We
      retrospectively reviewed the charts of adolescent males with a diagnosis of
      unilateral left varicocele and ultrasound testis volume measurements seen during
      a 10-year period. A total of 161 boys underwent at least 2 testicular ultrasounds
      as part of the evaluation for left varicocele. Patients were excluded from study
      for a history of inguinal/scrotal pathology or endocrinopathy that could affect
      testicular size. Sonographic testicular volume was calculated using the Lambert
      volume (length x width x height x 0.71). The resulting volumes were compared to
      previously published criteria for surgical repair (15%, 20% and 2 cc size
      differentials). RESULTS: Of the 71 boys with 3 followup ultrasounds 38 (54%)
      initially had a 15% or greater volume differential. After nonsurgical followup
      with ultrasounds for 2 years 60 boys (85%) had testicular volume differentials in
      the normal range (less than 15%). Of the patients 71% were spared potential
      surgery by size criteria and 50% were spared surgery by the same 15% volume
      differential criteria. CONCLUSIONS: Adolescent males with unilateral left
      varicocele often demonstrate asynchronous testicular growth that usually
      equalizes in time. Therefore, sonographic testicular size measurement at a single
      point during adolescence is insufficient to determine the need for
      varicocelectomy. When contemplating varicocelectomy we recommend at least 2, and
      preferably 3, testicular volume measurements 1 year apart to establish accurately
      decreased left testicular volume compared to a normal right testis.

PMID- 18639289
TI  - Transurethral autologous myoblast injection for treatment of urinary incontinence
      in children with classic bladder exstrophy.
AB  - PURPOSE: The application of autologous myoblasts is an area of active research
      that may represent an improved alternative for the treatment of urinary
      incontinence. In this study we investigated the effectiveness of autologous
      myoblast injection for the treatment of urinary incontinence in children with
      classic bladder exstrophy. MATERIALS AND METHODS: Seven boys and 1 girl with
      persistent urinary incontinence were entered in the study. All children had
      undergone staged bladder repair and bladder neck reconstruction, and 5 patients
      had received 1 to 3 transurethral injections of bulking agent. Autologous
      myoblasts were isolated from abdominal muscle biopsy and cultured before
      endourethral injection. After the procedure patients underwent pelvic floor
      electrical stimulation and continued pelvic floor exercises that had been started
      at least 1 year before injection. The clinical outcomes (based on a 24-hour
      voiding diary), and cystometric and urodynamic studies were evaluated. Followup
      ranged from 12 to 18 months (average 15.3). RESULTS: There was a significant,
      time dependent improvement in urinary continence. At final followup all 7 boys
      (88% of patients) were socially dry (daytime dryness more than 3 hours),
      including 3 (38%) who were completely dry. Urodynamic studies revealed an
      increase in mean bladder capacity (p <0.001), detrusor leak point pressure (p
      <0.001) and average maximum urinary flow (p <0.01). All 7 boys (vs only 2
      patients preoperatively) achieved normal voiding with demonstrable voiding
      detrusor contraction in the presence of a compliant stable bladder (p <0.05).
      CONCLUSIONS: Our results suggest that transurethral autologous myoblast injection
      is a valid option for the treatment of structural urinary incontinence in
      children with classic bladder exstrophy. However, favorable preoperative
      urodynamic profiles and postoperative pelvic floor electrical stimulation may
      have contributed to the outcome in this series.

PMID- 18639290
TI  - Intravesical oxybutynin for children with poorly compliant neurogenic bladder: a
      systematic review.
AB  - PURPOSE: Children with neurogenic bladder and poor bladder compliance are usually
      treated with bladder catheterization and oral anticholinergic medication. They
      may become nonresponders to the drug or present with severe side effects. We
      evaluated the effectiveness and tolerability of intravesical oxybutynin in
      children with poorly compliant neurogenic bladder. MATERIALS AND METHODS: We
      conducted a search of MEDLINE, EMBASE, CINAHL, SciELO, dissertations/theses in
      ProQuest, LILACS, the Cochrane Library, protocol registries and the gray
      literature. Two reviewers independently assessed study quality and extracted
      data. RESULTS: Eight studies (2 prospective, 6 retrospective) assessed the
      effectiveness and side effects of intravesical oxybutynin in children with
      neurogenic bladder. A total of 297 children started treatment, of whom 22% (66
      patients) discontinued therapy, with 9% (28) quitting due to systemic side
      effects. Mean change in bladder compliance (primary outcome) was reported in only
      2 studies (+7.4 and +7.5 ml/cm H(2)O). The pooled mean change in pressure at
      maximum bladder capacity was -16.4 cm H(2)O (95% CI -22.8 to -10.0). Incontinence
      improved significantly in most studies, with "dry and improved" rates ranging
      from 61% to 83%. The funnel plot of pressure at maximum bladder capacity
      suggested no publication bias. CONCLUSIONS: Adjunctive intravesical oxybutynin
      therapy increased mean maximum bladder capacity and decreased bladder pressure in
      children with neurogenic bladder. However, identified studies offered a low level
      of evidence, with most being poorly reported retrospective case series with
      potential biases. Although the incidence of side effects was lower with the
      intravesical route, side effects are still possible and should be discussed with
      patients and families. The evidence available is insufficient to recommend this
      therapy. Research of more sound study design such as a randomized controlled
      trial should be conducted to assess the efficacy and side effects of intravesical
      oxybutynin in children.

PMID- 18639291
TI  - Clinical inconsistency of lower urinary tract symptoms between questionnaire and
      bladder diary in children with nocturnal enuresis.
AB  - PURPOSE: Classification of pediatric enuresis into monosymptomatic nocturnal
      enuresis and nonmonosymptomatic nocturnal enuresis is crucial for management
      because these cases differ in many clinical respects. However, correct
      classification is frequently confused based on questionnaire and/or bladder
      diary. We tested the consistency of information obtained on lower urinary tract
      symptoms between our questionnaire and bladder diary. MATERIALS AND METHODS: A
      total of 108 physically and neurologically normal patients (mean age 7.2 years)
      with enuresis were included in the study. All patients filled out the
      questionnaire and 3-day bladder diary completely. Our questionnaire included
      items on urinary frequency, daytime incontinence and voiding postponement. A
      total of 93 patients underwent uroflowmetry and residual urine measurements. We
      analyzed information on lower urinary tract symptoms from the questionnaire and
      the bladder diary, as well as the uroflowmetry results. RESULTS: The percentage
      of children with nonmonosymptomatic nocturnal enuresis was 89.8% and 68.5% based
      on the questionnaire and bladder diary, respectively. In comparisons between the
      questionnaire and bladder diary we did not observe any significant consistency
      regarding urinary frequency (p = 0.912), daytime incontinence (p = 0.356) or
      voiding postponement (p = 0.505). Maximum voided volume, average voided volume
      and percent maximum voided volume/expected bladder capacity of children with
      monosymptomatic nocturnal enuresis were significantly higher than in those with
      nonmonosymptomatic nocturnal enuresis based on the bladder diary (p = 0.006,
      0.001 and 0.041, respectively). By contrast, no significant difference was found
      between children with monosymptomatic and nonmonosymptomatic nocturnal enuresis
      based on the questionnaire (p = 0.559, 0.597 and 0.947, respectively).
      CONCLUSIONS: Significant discrepancies in lower urinary tract symptoms were
      observed between the questionnaire and bladder diary. Therefore, a detailed
      history and discussion with the patient and family should be performed to
      correlate with the questionnaire and bladder diary for the proper treatment of
      children with enuresis. An updated questionnaire containing a detailed scoring
      system may be needed.

PMID- 18639292
TI  - The Pediatric Penile Perception Score: an instrument for patient self-assessment
      and surgeon evaluation after hypospadias repair.
AB  - PURPOSE: The aim of this study was to develop and evaluate an instrument that
      allows assessment and comparison of penile perception of patients, parents and
      surgeons. MATERIALS AND METHODS: A total of 77 boys 6 to 17 years old who had
      undergone hypospadias repair were interviewed by a psychologist with a
      standardized questionnaire concerning penile self-perception with regard to
      meatus, glans, skin and general appearance. The Pediatric Penile Perception Score
      was derived from the sum of these 4 items. The results were compared with a
      control group of age matched boys following inguinal hernia repair. Parents were
      asked via questionnaire to report the penile appearance of their son using the
      Pediatric Penile Perception Score. A total of 56 patients accepted standardized
      photographic documentation, and their pictures were sent for evaluation with the
      Pediatric Penile Perception Score to 6 blinded urologists. RESULTS: The Pediatric
      Penile Perception Score allowed us to assess perception of the genitalia by
      patients, parents and urologists. Statistical analysis of the Pediatric Penile
      Perception Score assigned by the urologist revealed good interrater reliability
      (interclass correlation 0.75 to 0.88) and stability (r = 0.59 to 0.83).
      Intercorrelation of the items "meatus," "glans" and "skin" with "general
      appearance" was good among the boys, parents and urologists. Patients with
      hypospadias expressed high satisfaction with the penile appearance, which did not
      differ significantly from age matched controls. However, parents and urologists
      were less satisfied with the penile appearance than were the patients themselves.
      CONCLUSIONS: The Pediatric Penile Perception Score is a reliable instrument to
      assess penile self-perception in children after hypospadias repair, and for
      appraisal of the surgical result by parents and uninvolved urologists.

PMID- 18639293
TI  - Medicare reimbursement changes for ambulatory surgery centers and remuneration to
      urological physician-owners.
AB  - PURPOSE: To decrease the cost of surgical care Medicare has introduced a new
      facility fee schedule for ambulatory surgical centers. This prospective payment
      system increases reimbursement for many urological procedures, while decreasing
      reimbursement for others. All stakeholders, including physicians, the Medicare
      program and hospitals, will be affected by these changes. MATERIALS AND METHODS:
      Using the Agency for Healthcare Research and Quality State Ambulatory Surgery
      Databases we identified Medicare patients in Florida who underwent urological
      procedures in ambulatory surgical centers from 1998 to 2005. Three facility
      groupings were created, including urology dominant, multispecialty and other
      specialty dominant. The impact of reimbursement changes at the procedure and
      facility levels was assessed using 2005 data. Projections of ambulatory surgical
      center use and reimbursement in 2008 were then generated using all available
      data. RESULTS: In 2008 we project total payments by Medicare to increase by
      $4,233,080 (26%, range 22% to 32%) under the new reimbursement system compared to
      the old system. At the facility level reimbursement to multispecialty facilities
      should increase substantially (49%), while urology specialty facilities will
      receive less benefit (10% increase). Compared to multispecialty facilities, at
      urology specialty facilities a higher proportion of cases is performed for which
      reimbursement is set to decrease. CONCLUSIONS: Under the new payment scheme for
      ambulatory surgical centers winners and losers emerge. Facilities with
      diversified procedure mixes will find increased revenue, while those with less
      diversification will find slower growth to their revenue streams. In contrast to
      the desire of the Medicare program to decrease surgical costs, the new program
      may increase the payments made for urological surgery.

PMID- 18639294
TI  - The outcome of intracytoplasmic sperm injection using occasional spermatozoa in
      the ejaculate of men with spermatogenic failure.
AB  - PURPOSE: Men with spermatogenic failure so profound that they are considered as
      having nonobstructive azoospermia occasionally have spermatozoa in the ejaculate.
      We compared intracytoplasmic sperm injection outcomes following the injection of
      ejaculated or surgically retrieved spermatozoa from these men. MATERIALS AND
      METHODS: A study was performed of intracytoplasmic sperm injection cycles with no
      spermatozoa on initial semen analysis and 100 or fewer following centrifugation
      (cryptozoospermia). Only 16 couples that underwent intracytoplasmic sperm
      injection cycles with ejaculated spermatozoa and cycles with testicular
      spermatozoa were included. RESULTS: Initial analysis was done to compare outcomes
      between the 2 semen origins. There was no difference in the rate of normal or
      abnormal fertilization between the 2 groups. The rate of clinical pregnancies
      seemed to favor testicular spermatozoa (47.4% vs 20.8%), although results were
      not significant. When a comparison was performed between the first testicular
      cycle and the ejaculated cycle closest in time to the cycle with testicular
      spermatozoa, a higher rate of normal fertilization with testicular spermatozoa
      was observed (60.9% vs 48.5%, p <0.05). Also, in this comparison a clear trend
      toward a higher percent of clinical pregnancies and deliveries in the testicular
      group was observed (50.0% vs 14.3%). CONCLUSIONS: Transit through the male
      genital tract did not enhance the ability of ejaculated spermatozoa to achieve
      fertilization with intracytoplasmic sperm injection compared to that of
      testicular spermatozoa in men with severely impaired production. In ejaculated
      samples a lower number of spermatozoa available resulted in an impaired chance of
      achieving pregnancy. Using testicular spermatozoa may be a reasonable alternative
      for couples in whom multiple attempts at intracytoplasmic sperm injection have
      failed using ejaculated sperm from men with cryptozoospermia.

PMID- 18639295
TI  - Primary penile venous leakage surgery with crural ligation in men with erectile
      dysfunction.
AB  - PURPOSE: We report our long-term results of penile venous surgery with crural
      ligation for primary venous leakage in men with erectile dysfunction. MATERIALS
      AND METHODS: The study included 26 men with erectile dysfunction who underwent
      penile venous surgery for primary venous leakage with at least 1 year of
      postoperative followup at a single university hospital. All patients underwent
      penile venous surgery, including resection of the superficial and deep dorsal
      veins, ligation of the cavernous vein and 2 crura proximal to the entrance of the
      cavernous artery with umbilical tapes, and preservation of the dorsal artery and
      nerve on each side. Postoperative evaluation included the 5-item version of the
      International Index of Erectile Function, physical examination, duplex ultrasound
      and cavernosography, as necessary. Improvement in erectile functions and patient
      satisfaction were also assessed as complete, partial and none. RESULTS: The mean
      +/- SD International Index of Erectile Function score increased from 6.7 +/- 3.61
      to 16.3 +/- 6.4, which was a highly statistically significant difference (p =
      0.001). Postoperatively erectile function improved completely in 11 men (42.3%)
      and partially in 8 (30.8%), and it remained unchanged in 7 (26.9%). A total of 12
      patients maintained satisfactory erection with phosphodiesterase-5 inhibitors,
      which had not been effective preoperatively. Patient satisfaction with no
      additional treatment or with phosphodiesterase-5 inhibitors was complete in 15
      (57.7%) and partial in 8 (30.7%), while 3 (11.6%) were not satisfied with
      surgery. These 3 patients underwent penile prosthesis implantation with a 3-piece
      device. CONCLUSIONS: Penile venous surgery with crural ligation for venous
      leakage has excellent long-term results and patient satisfaction. Therefore, it
      should be offered to young men with primary cavernous erectile dysfunction. Young
      patients with normal penile arterial system and no risk factors such as diabetes
      have the best chance for improved postoperative success.

PMID- 18639296
TI  - Effect of vardenafil on blood pressure profile of patients with erectile
      dysfunction concomitantly treated with doxazosin gastrointestinal therapeutic
      system for benign prostatic hyperplasia.
AB  - PURPOSE: We investigated the effect of the combination of the doxazosin
      gastrointestinal therapeutic system and 10 mg vardenafil on the hemodynamic
      status of patients with benign prostatic hyperplasia and erectile dysfunction.
      MATERIALS AND METHODS: This was a double-blinded, randomized, placebo controlled
      crossover trial. Patients with benign prostatic hyperplasia and erectile
      dysfunction treated with the doxazosin gastrointestinal therapeutic system on a
      regular basis, with no other antihypertensive events, were recruited. Subjects
      took 10 mg vardenafil or placebo in a randomized crossover fashion with a washout
      period of at least 7 days between each treatment. The supine and standing blood
      pressure of the subjects was recorded from 1 hour before to 6 hours after the
      administration of vardenafil or placebo. The primary outcome of the study was the
      maximal change in standing systolic blood pressure of the subjects from 1 half
      hour before to 6 hours after the administration of drugs. RESULTS: A total of 37
      patients, 25 (67.6%) and 12 (32.4%) on the doxazosin gastrointestinal therapeutic
      system at 4 mg and 8 mg, respectively, completed the trial. The combination drug
      therapy resulted in a maximal decrease in standing systolic blood pressure of
      6.18 mm Hg (95% CI -12.02, -0.33; p = 0.039). Only 1 patient had an asymptomatic
      standing systolic blood pressure of less than 85 mm Hg. Otherwise no symptomatic
      hypotension or clinically significant adverse cardiovascular event was observed
      during the study. CONCLUSIONS: In patients on the doxazosin gastrointestinal
      therapeutic system for benign prostatic hyperplasia a single 10 mg dose of
      vardenafil had no symptomatic hemodynamic effects.

PMID- 18639297
TI  - Effect of tolterodine extended release with or without tamsulosin on measures of
      urgency and patient reported outcomes in men with lower urinary tract symptoms.
AB  - PURPOSE: We evaluated the efficacy of tolterodine extended release and/or
      tamsulosin on micturition related urgency episodes, urgency severity and patient
      reported outcomes in men who met entry criteria for prostatic enlargement and
      overactive bladder trials. MATERIALS AND METHODS: Men 40 years old or older with
      an International Prostate Symptom Score of 12 or greater, frequency (8 or more
      voids per 24 hours) and urgency (3 or more episodes per 24 hours) with or without
      urgency urinary incontinence were randomized to placebo, 4 mg tolterodine
      extended release, 0.4 mg tamsulosin or tolterodine extended release plus
      tamsulosin for 12 weeks. Subjects completed 5-day diaries; the Patient Perception
      of Bladder Condition and Urgency Perception Scale at baseline, and weeks 1, 6 and
      12; Overactive Bladder Questionnaire at baseline, and weeks 6 and 12; Perception
      of Treatment Satisfaction question at weeks 1, 6 and 12; and Willingness to
      Continue question at week 12. Subjects rated the urgency associated with each
      micturition on a 5-point scale and micturition related urgency episodes were
      those rated 3 or greater. Urgency severity was measured using frequency-urgency
      sum, defined as the sum of urgency ratings for all micturitions. RESULTS:
      Compared with placebo, tolterodine extended release plus tamsulosin significantly
      reduced daytime and nocturnal micturition related urgency episodes as well as
      frequency-urgency sum at weeks 1, 6 and 12. It also improved Patient Perception
      of Bladder Condition scores at weeks 1, 6 and 12; improved Urgency Perception
      Scale and Overactive Bladder Questionnaire, Symptom Bother and Health Related
      Quality of Life scores at weeks 6 and 12; and increased the percentage of
      subjects who reported treatment satisfaction at weeks 6 and 12, and willingness
      to continue at week 12. CONCLUSIONS: Treatment with tolterodine extended release
      plus tamsulosin significantly improved urgency variables and patient reported
      outcomes in men meeting entry criteria for overactive bladder and prostatic
      enlargement trials.

PMID- 18639298
TI  - Long-term treatment with finasteride results in a clinically significant
      reduction in total prostate volume compared to placebo over the full range of
      baseline prostate sizes in men enrolled in the MTOPS trial.
AB  - PURPOSE: In the present analysis we examined data from the MTOPS (Medical Therapy
      of Prostatic Symptoms) trial to determine the effect of long-term finasteride
      treatment, either alone or in combination with doxazosin, on total prostate
      volume across the full range of baseline total prostate volume values in men
      enrolled in this study. MATERIALS AND METHODS: In this trial a total of 3,047
      patients with lower urinary tract symptoms were randomized to placebo, doxazosin
      (4 to 8 mg), finasteride (5 mg) or the combination of doxazosin and finasteride
      (average length of treatment 4.5 years). Total prostate volume was measured by
      transrectal ultrasound in all patients at baseline, yearly and at study end or at
      termination of participation. RESULTS: Long-term treatment with finasteride led
      to a consistent reduction of approximately 25% in total prostate volume compared
      to placebo in men with a relatively small prostate (less than 25 to 30 ml), as
      well as in those with a moderate size (30 to less than 40 ml) or enlarged
      prostate (40 ml or greater) at baseline. CONCLUSIONS: In this MTOPS data analysis
      long-term (more than 4 years) treatment with finasteride, either alone or in
      combination with doxazosin, led to a consistent, clinically significant reduction
      in total prostate volume compared to placebo in patients with lower urinary tract
      symptoms and benign prostatic hyperplasia whose baseline prostate size ranged
      from relatively small (less than 25 to 30 ml) to enlarged (40 ml or greater).

PMID- 18639299
TI  - Effects of photoselective vaporization of the prostate on urodynamics in patients
      with benign prostatic hyperplasia.
AB  - PURPOSE: We evaluated the effects of photoselective vaporization of the prostate
      on efficacy outcomes and urodynamic parameters in patients with benign prostatic
      hyperplasia. MATERIALS AND METHODS: The efficacy and morbidity of photoselective
      vaporization of the prostate were prospectively analyzed in 135 patients who
      underwent this therapy. Treatment efficacy was assessed regarding outcome
      variables, including International Prostate Symptom Score, quality of life score,
      peak urinary flow rate and post-void residual urine volume 3, 6 and 12 months
      postoperatively. Urodynamic evaluations, including cystometry and a pressure flow
      study, were performed before and after the operation in 78 patients.
      Perioperative values and postoperative complications were also noted. RESULTS:
      Significant improvement was observed in all outcome variables with significant
      relief of bladder outlet obstruction and detrusor overactivity, and a minimal
      change in detrusor contractility following photoselective vaporization of the
      prostate. The preoperative and postoperative overall rate of detrusor
      overactivity was 47.4% and 26.9%, respectively. The median preoperative and
      postoperative degree of obstruction according to the Schafer nomogram was 4 (IQR
      3, 4) and 1 (IQR 0, 1), respectively. Decreases in serum sodium and hemoglobin
      were negligible. Two patients required intervention for postoperative bleeding.
      There were 2 newly documented cases of urethral stricture. Two patients required
      reoperation for postoperative dysuria. CONCLUSIONS: Photoselective vaporization
      of the prostate is considered a safe and effective treatment with minimal
      bleeding and no hyponatremia, thus providing successful relief of bladder outlet
      obstruction and detrusor overactivity without affecting detrusor contractility in
      patients with benign prostatic hyperplasia.

PMID- 18639300
TI  - Assessment of early continence after reconstruction of the periprostatic tissues
      in patients undergoing computer assisted (robotic) prostatectomy: results of a 2
      group parallel randomized controlled trial.
AB  - PURPOSE: Several case series have shown that reconstruction of the anterior or
      posterior periprostatic tissues facilitates early return of urinary continence
      after radical prostatectomy. We conducted a randomized clinical trial comparing
      early continence rates in patients undergoing urethrovesical anastomosis with or
      without periprostatic reconstruction. MATERIALS AND METHODS: A total of 116
      consecutive patients undergoing computer assisted (robotic) prostatectomy
      performed by 1 of 2 experienced surgeons were randomized to single (without
      periprostatic reconstruction) or double layer (with periprostatic tissue
      reconstruction) urethrovesical anastomosis. Urinary loss was measured by pad
      weight at 1, 2, 7 and 30 days after catheter removal. Patients and data gatherers
      were blinded to treatment allocation. RESULTS: There were 57 patients randomized
      to the single and 59 to the double layer anastomosis group. All patients
      completed the study and followup. Using the conventional definition of urinary
      continence (0 to 1 pads daily) 26% and 34%, 49% and 46%, 51% and 54%, and 74% and
      80% of patients undergoing single layer or double layer anastomoses were
      continent at 1, 2, 7 and 30 days, respectively (p >0.1). Of the patients in the 2
      groups 7% and 15%, 14% and 14%, 16% and 20%, and 47% and 42% had no urinary
      leakage (0 gm or 0 pads daily) at these intervals, respectively (p >0.1). In each
      group 1 patient required prolonged catheterization because of cystographic
      evidence of anastomotic leakage. There were no other complications. CONCLUSIONS:
      Early urinary continence rates were high in patients undergoing single or double
      layer urethrovesical anastomosis. We found no improvement in early continence
      rates with reconstruction of the periprostatic tissues.

PMID- 18639301
TI  - Air charged and microtip catheters cannot be used interchangeably for urethral
      pressure measurement: a prospective, single-blind, randomized trial.
AB  - PURPOSE: We determined and compared urethral pressure measurements using air
      charged and microtip catheters in a prospective, single-blind, randomized trial.
      MATERIALS AND METHODS: A consecutive series of 64 women referred for urodynamic
      investigation underwent sequential urethral pressure measurements using an air
      charged and a microtip catheter in randomized order. Patients were blinded to the
      type and sequence of catheter used. Agreement between the 2 catheter systems was
      assessed using the Bland and Altman 95% limits of agreement method. RESULTS:
      Intraclass correlation coefficients of air charged and microtip catheters for
      maximum urethral closure pressure at rest were 0.97 and 0.93, and for functional
      profile length they were 0.9 and 0.78, respectively. Pearson's correlation
      coefficients and Lin's concordance coefficients of air charged and microtip
      catheters were r = 0.82 and rho = 0.79 for maximum urethral closure pressure at
      rest, and r = 0.73 and rho = 0.7 for functional profile length, respectively.
      When applying the Bland and Altman method, air charged catheters gave higher
      readings than microtip catheters for maximum urethral closure pressure at rest
      (mean difference 7.5 cm H(2)O) and functional profile length (mean difference 1.8
      mm). There were wide 95% limits of agreement for differences in maximum urethral
      closure pressure at rest (-24.1 to 39 cm H(2)O) and functional profile length (
      7.7 to 11.3 mm). CONCLUSIONS: For urethral pressure measurement the air charged
      catheter is at least as reliable as the microtip catheter and it generally gives
      higher readings. However, air charged and microtip catheters cannot be used
      interchangeably for clinical purposes because of insufficient agreement. Hence,
      clinicians should be aware that air charged and microtip catheters may yield
      completely different results, and these differences should be acknowledged during
      clinical decision making.

PMID- 18639302
TI  - Burch colposuspension does not provide any additional benefit to pelvic organ
      prolapse repair in patients with urinary incontinence: a randomized surgical
      trial.
AB  - PURPOSE: We evaluated the impact of Burch colposuspension as an anti-incontinence
      measure in patients with urinary incontinence undergoing abdominal surgery for
      pelvic organ prolapse repair. MATERIALS AND METHODS: A total of 47 women with
      pelvic organ prolapse and urinary incontinence were randomly assigned to
      abdominal pelvic organ prolapse repair and concomitant Burch colposuspension (24
      patients, group A) or pelvic organ prolapse repair alone without an anti
      incontinence procedure (23 patients, group B). They were followed up at 3, 6 and
      9 months after surgery, and then annually. The primary outcome measures were
      anatomical outcome and changes in incontinence status as indicated by a bladder
      diary, the number of daily pads and the stress test. Secondary end points were
      changes in subjective symptoms and quality of life as measured by the Urogenital
      Distress Inventory and the Incontinence Impact Questionnaire. RESULTS: In group A
      13 of 24 patients (54.2%) were still incontinent after surgery compared with 9 of
      23 (39.1%) in group B. The intragroup difference was significant (group A p =
      0.003, group B p = 0.0001), but there was no significant intergroup difference (p
      = 0.459 for A vs B). No significant intergroup difference emerged in anatomical
      outcome. Urogenital Distress Inventory and Incontinence Impact Questionnaire
      scores improved in both groups (p = 0.0001) but the intergroup difference was not
      significant in either questionnaire (p = 0.769 and p = 0.327, respectively).
      CONCLUSIONS: Burch colposuspension does not provide any additional benefit in
      pelvic organ prolapse repair in patients with urinary incontinence.

PMID- 18639303
TI  - The effect of concomitant prolapse repair on sling outcomes.
AB  - PURPOSE: We analyzed the effect of concomitant prolapse surgery performed at the
      time of sling surgery on short-term postoperative outcomes in women with urinary
      incontinence. MATERIALS AND METHODS: We analyzed 1999 to 2001 Medicare claims
      data on a 5% national random sample of female beneficiaries who underwent sling
      procedures. Subjects were tracked for 12 months after surgery to assess short
      term complications. Concomitant prolapse repairs and prolapse repairs performed
      in the first 12 months after sling surgery were identified by CPT-4 procedure
      codes. Postoperative complications and treatments were identified by ICD-9
      diagnosis codes and CPT-4 procedure codes, respectively. Bivariate and
      multivariate analyses were performed to measure the effect of concomitant
      prolapse surgery on sling outcomes. RESULTS: Concomitant prolapse repairs were
      performed in 34.4% of sling cases. Women who underwent prolapse repair at the
      time of the sling surgery were significantly more likely to be diagnosed with
      postoperative outlet obstruction (9.4% vs 5.5%, p <0.007) than those who did not.
      Women who underwent concomitant prolapse repair were less likely to undergo a
      repeat procedure for stress incontinence in postoperative year 1 (4.7% vs 10.2%,
      p = 0.0005). Multivariate analysis revealed that women who underwent prolapse
      repair at the time of the sling surgery were significantly less likely to undergo
      a reoperation for prolapse within 1 year after the sling surgery (OR 0.31, 95% CI
      0.22-0.44). CONCLUSIONS: Our findings suggest that addressing prolapse at the
      time of stress incontinence surgery may avoid an early repeat operation for
      either prolapse or stress incontinence. However, rates of postoperative outlet
      obstruction are higher.

PMID- 18639304
TI  - Heavy metal contamination from gold mining recorded in Porites lobata skeletons,
      Buyat-Ratototok district, North Sulawesi, Indonesia.
AB  - Shallow marine sediments and fringing coral reefs of the Buyat-Ratototok district
      of North Sulawesi, Indonesia, are affected by submarine disposal of tailings from
      industrial gold mining and by small-scale gold mining using mercury amalgamation.
      Between-site variation in heavy metal concentrations in shallow marine sediments
      was partially reflected by trace element concentrations in reef coral skeletons
      from adjacent reefs. Corals skeletons recorded silicon, manganese, iron, copper,
      chromium, cobalt, antimony, thallium, and lead in different concentrations
      according to proximity to sources, but arsenic concentrations in corals were not
      significantly different among sites. Temporal analysis found that peak
      concentrations of arsenic and chromium generally coincided with peak
      concentrations of silica and/or copper, suggesting that most trace elements in
      the coral skeleton were incorporated into detrital siliciclastic sediments,
      rather than impurities within skeletal aragonite.

PMID- 18639305
TI  - Spatial and vertical distribution of organochlorine pesticides in sediments from
      Daya Bay, South China.
AB  - The spatial and vertical distribution of organochlorine pesticides (OCPs) has
      been investigated in Daya Bay, China. The concentration of total OCPs in surface
      sediment range from 16.66 to 44.04 ng/g dry weight with a mean concentration of
      26.60 ng/g. DDTs and HCHs were the predominant species. The ratios of
      (DDD+DDE)/DDT reflected a cocktail input pattern of fresh and weathered DDTs. The
      predominant alpha-HCH and the alpha/beta-HCH ratios indicated that the technical
      HCH contamination was mainly due to historical usage, although there was fresh
      input of lindane. The variation profiles of concentrations showed that OCPs were
      extensively applied between the late 1950s and early 1980s in China. A recent
      increasing trend in concentrations of DDTs and HCHs was found in both cores. The
      increasing ratios of (DDE+DDD)/DDT with corresponding decreases of DDE/DDT ratio
      implied that most of the DDTs deposited after their production ban were more
      likely "weathered" DDTs derived from soil residues.

PMID- 18639306
TI  - Mapping mental number line in physical space: vertical and horizontal visual
      number line orientation in asymptomatic individuals with HIV.
AB  - Multiple studies have implicated frontostriatal dysfunction in human
      immunodeficiency virus (HIV) and described cognitive deficits with a focus on
      executive function and memory. Remarkably little is known about visuospatial and
      number processing in HIV, though these capacities are also supported by
      frontostriatal circuits and their parietal connections. We investigated the
      relation of numerical and spatial cognition in asymptomatic individuals with HIV
      and explored physical and mental number orientation using several modes of
      presentation and response: mental number line bisection, physical line bisection,
      and physical number line orientation on visually-presented horizontal and
      vertical number lines. The asymptomatic HIV+ group was significantly slower and
      produced more errors on visuospatial and number processing tasks than the HIV-
      group (n=37/group). Both groups showed significant correlations between number
      processing and visuospatial performance. These findings demonstrate that HIV
      related brain damage early in the disease course can alter the spatial
      representation of numerical distance, providing evidence for disruption of
      frontostriatal circuits and their parietal projections underlying numerical
      processing in HIV. Besides disease-related effects, this study demonstrates that
      the physical number line preserves its numerical and spatial integrity in both
      the vertical and horizontal physical dimensions, as all participants exhibited
      underestimation of numerical distance, i.e. leftward bias (for horizontal
      presentation) and downward bias (for vertical). Our results also revealed a
      dissociation between the processing components of numerical distance and physical
      space, suggesting differentiation between the neural networks involved in number
      lines and physical line orientation.

PMID- 18639307
TI  - Caffeoyl arbutin and related compounds from the buds of Vaccinium dunalianum.
AB  - Dunalianosides A-I (1-9), esters of arbutin and related phenolic glucosides, were
      isolated from the buds of Vaccinium dunalianum Wight (Ericaceae) together with 20
      known compounds, and their structures were established on the basis of 1- and 2D
      NMR spectroscopic evidence. Dunalianosides F-H were dimers of p-hydroxyphenyl 6-O
      trans-caffeoyl-beta-D-glucopyranoside (10). The latter was obtained in
      extraordinary high yield (22% of dry weight), and dunalianoside I (9) was found
      to be a conjugate of arbutin with an iridoid glucoside.

PMID- 18639308
TI  - Braunicetals: acetals from condensation of macrocyclic aldehydes and terpene
      diols in Botryococcus braunii.
AB  - Two series of braunicetals were isolated from the green microalga Botryococcus
      braunii. Based on spectroscopic and chemical evidence, their structures were
      determined to be acetals formed by the condensation of C32 and C34 macrocyclic
      aldehydes with C33 and C34 methylated squalene diols (series I), or a C40
      lycopaene diol (series II).

PMID- 18639309
TI  - [Juvenile myoclonic epilepsy in a patient with history of infantile hemiplegia].
AB  - INTRODUCTION: The 1989 International Classification of Epilepsies and Related
      Syndromes considers normal cognitive, neurologic and anatomic findings to be
      prerequisites for the diagnosis of idiopathic forms of epilepsy. CASE REPORT: We
      report the case of a woman with juvenile myoclonic epilepsy (JME) and a history
      of infantile hemiplegia. When she was a teenager, she had two generalized tonic
      clonic seizures, later followed by a few seizures with loss of consciousness
      misinterpreted as complex partial seizures. Physical examination revealed right
      hemiparesis. A CT scan documented a left rolandic infarction and a wrong
      diagnosis of focal epilepsy was made. At 20 years, a nap video-EEG was performed.
      A burst of generalized spike-waves was recorded on awakening. Photic stimulation
      and watching a Japanese cartoon on television disclosed a marked photoparoxysmal
      response associated with myoclonic jerks. Myoclonic jerks were in fact known by
      the patients but unreported. She had jerks on roads with trees due to
      shade/sunlight alternance. A diagnosis of JME was made. CONCLUSION: This
      observation illustrates that patients' situation with a presumed genetic
      predisposition for JME are at equal risk for brain lesions as others subjects.
      Misdiagnosis of focal epilepsy may have dramatic consequences in patient with
      JME, as some patients will be aggravated by inadequate antiepileptic drugs.

PMID- 18639311
TI  - Immune response following miltefosine therapy in a patient with post-kala-azar
      dermal leishmaniasis.
AB  - We report a case of post-kala-azar dermal leishmaniasis in which real-time PCR
      was exploited to measure changes in cytokine transcripts in lesion tissue before
      and after oral miltefosine treatment. Unlike antimonial therapy elevated levels
      of IFNgamma transcripts were noted, whereas TNFalpha, IL-10 and transforming
      growth factor-beta declined similar to that observed after therapy with
      antimonials. A significant increase in IFNgamma and CD40 levels seen after
      miltefosine therapy could enhance parasite clearance. The patient remained normal
      after 18 months of follow-up.

PMID- 18639310
TI  - Indoor air pollution from biomass fuel smoke is a major health concern in the
      developing world.
AB  - One-third of the world's population burn organic material such as wood, dung or
      charcoal (biomass fuel) for cooking, heating and lighting. This form of energy
      usage is associated with high levels of indoor air pollution and an increase in
      the incidence of respiratory infections, including pneumonia, tuberculosis and
      chronic obstructive pulmonary disease, low birthweight, cataracts, cardiovascular
      events and all-cause mortality both in adults and children. The mechanisms behind
      these associations are not fully understood. This review summarises the available
      information on biomass fuel use and health, highlighting the current gaps in
      knowledge.

PMID- 18639312
TI  - Lactam ergot alkaloids (ergopeptams) as predominant alkaloids in sclerotia of
      Claviceps purpurea from Norwegian wild grasses.
AB  - Four major alkaloids in the extracts from sclerotia of Claviceps purpurea, picked
      from wild grasses, have been identified as lactam (non-cyclol) ergot alkaloids.
      The structural information was obtained from ion trap MS and NMR spectroscopy.
      The data for one of the lactam ergot alkaloids were coinciding with ergocristam
      [N-(lysergyl-valyl)-cyclo(phenylalanyl-prolyl)]. The structural information of
      two further lactam alkaloids was suggestive of either alpha- or beta-ergocryptam
      [N-(lysergyl-valyl)-cyclo(leucyl-prolyl) or N-(lysergyl-valyl)-cyclo(isoleucyl
      prolyl)] and ergoannam [N-(lysergyl-leucyl)-cyclo(leucyl-prolyl) or N-(lysergyl
      isoleucyl)-cyclo(isoleucyl-prolyl)]. The constitution of the fourth lactam ergot
      alkaloid corresponded to N-(lysergyl-isoleucyl)-cyclo(phenylalanyl-prolyl), a new
      ergopeptam, which has not been described before. Additionally, the cyclol
      analogue of the new ergopeptam was detected in the extracts and has been
      identified on the basis of its product ion spectrum from fragmentation of
      [M+H](+). The study described in this paper shows that lactam ergot alkaloids may
      not only be minor products of ergopeptine biosynthesis, as has been suggested
      hitherto, but may be major biosynthetic endproducts for some ergot strains. This
      is also the first report demonstrating the production of an ergot alkaloid that
      contains isoleucine as the second amino acid, i.e. the N-(lysergyl-isoleucyl)
      moiety, by parasitic, naturally growing C. purpurea. This unusual type of ergot
      alkaloid has so far only been found in saprophytic cultures of C. purpurea.

PMID- 18639313
TI  - Identification and quantification of new polybrominated dimethoxybiphenyls
      (PBDMBs) in marine mammals from Australia.
AB  - Marine mammals from Queensland, Australia, are bioaccumulating elevated
      concentrations of a range of polybrominated natural products. In this study, we
      detected three new polybrominated dimethoxybiphenyls (PBDMBs) in the blubber of
      selected marine mammal samples which were identified as 2,6'-dimethoxy-3,3',5
      tribromobiphenyl (2,6'-diMeO-BB 36), 2,2'-dimethoxy-3,3'-dibromobiphenyl (2,2'
      diMeO-BB 36), and 6,6'-dimethoxy-3,3'-dibromobiphenyl (6,6'-diMeO-BB 11). These
      three PBDMBs are structurally related to the known natural product 2,2'-dimethoxy
      3,3',5,5'-tetrabromobiphenyl (2,2'-diMeO-BB 80). In the first part of this study,
      2,2'-diMeO-BB 80 was photochemically debrominated under UV irradiation. This
      resulted in seven of eight possible mono- to triBDMBs as debromination products.
      In the second part of this study, the structure of all PBDMBs debromination
      products was investigated. This was supported by synthesis of two diBDMB and one
      triBDMB via bromination and subsequent methylation of 2,2'-biphenyldiol.
      Structures of the remaining PBDMBs were tentatively assigned by considering the
      retention times, mass spectra and amounts formed during UV irradiation of 2,2'
      diMeO-BB 80 . In the third part of this study, blubber of marine mammals from
      Australia was analysed for PBDMBs using gas chromatography in combination with
      electron ionization mass spectrometry (GC/EI-MS) in the selected ion monitoring
      mode. In these samples, 2,2'-diMeO-BB 80 was found at concentrations of 200
      1800ngg(-1) lipid weight (lw). The latter represents the highest concentration
      reported for this compound in environmental samples. 6,6'-diMeO BB 11, 2,2'-diMeO
      BB 36, and 2,6'-diMeO BB 36 were present at approximately 7ngg(-1) lipids, or
      0.43-1.5% of diMeO-BB 80. No further PBDMBs were detected in the samples. The di-
      and triBDMBs identified in marine mammal blubber have not been reported as
      natural products. They may represent either new natural products or
      transformation products of 2,2'-diMeO-BB 80.

PMID- 18639314
TI  - A late Magdalenian perinatal human skeleton from Wilczyce, Poland.

PMID- 18639315
TI  - Surface ozone concentrations and ecosystem health: past trends and a guide to
      future projections.
AB  - This paper reviews current understanding of the sources and sinks of ozone in the
      troposphere, recent studies of long-term trends, and the factors which have to be
      taken into consideration when constructing and interpreting future models of
      ozone concentration. The factors controlling surface O(3) concentrations are
      discussed initially to provide a basis for the ensuing discussion, followed by a
      summary of the evidence for recent trends in ground-level ozone concentrations,
      i.e. over the past 3 decades, which have shown a significant increase in the
      annual average in 'background' air typical of the unpolluted northern hemisphere.
      Closer to precursor sources, although urban winter concentrations have increased,
      rural peak spring and summer concentrations during ozone 'episodes' have
      decreased markedly in response to emissions reductions. In order to determine
      whether such trends are meaningful, the statistical techniques for determining
      temporal trends are reviewed. The possible causes of long-term trends in ozone
      are then discussed, with particular reference to the use of chemistry-transport
      models to interpret past trends. Such models are also used to make predictions of
      future trends in surface ozone concentrations, but few are comprehensive in
      integrating future climate changes with changes in land use and in emissions of
      ozone precursors. Guidance is given on the likely effects of
      climate/precursor/chemistry interactions so that model predictions can be judged.

PMID- 18639316
TI  - Does mercury interact with the inhibitory effect of dichlorvos on Palaemon
      serratus (Crustacea: Decapoda) cholinesterase?
AB  - Mercury is one of the most hazardous metals that may contaminate estuarine
      ecosystems and induce toxic effects on wildlife organisms. It has been suggested
      that impairment of cholinesterase (ChE) activity may be involved in the resulting
      mercury toxicity. Following Palaemon serratus exposure to mercury chloride
      (HgCl2), no effect on ChE activity was observed whatever the concentration used
      (to 37.5 microM) or the time of exposure (to 7 days). By contrast, following 24 h
      exposure to dichlorvos, an organophosphate insecticide with a well-characterised
      anti-ChE action, decrease of ChE activity was observed until 30 to 40% basal
      activity, which seems to be the minimum activity required for prawn survival. In
      addition, HgCl2 does not affect dichlorvos toxicity and treatments with a mixture
      of both compounds can be interpreted as the sum of the two independent
      toxicities. Therefore, mercury and insecticide toxicities are independent and ChE
      activity from P. serratus eyes seems to be a reliable and sensitive biomarker for
      organophosphate insecticides even when organisms are simultaneously exposed to
      mercury.

PMID- 18639317
TI  - Changes in T-cell responses against human herpesvirus-8 correlate with the
      disease course of iatrogenic Kaposi's sarcoma in a patient with undifferentiated
      arthritis.
AB  - OBJECTIVES: To describe the first in-depth analysis of both the T-cell responses
      against human herpesvirus-8 (HHV-8) and the HHV-8 viral load in 1 patient who
      developed iatrogenic HHV-8-associated-Kaposi's sarcoma (KS) following
      immunosuppressive treatment for undifferentiated arthritis and to review the
      literature on iatrogenic KS (IKS). METHODS: T-cell responses against HHV-8 lytic
      and latent antigens were analyzed by ex vivo enzyme-linked immunospot (Elispot)
      and HHV-8 viral load was assessed by quantitative polymerase chain reaction, in
      sequential peripheral blood samples from a 55-year-old woman who developed
      skin/mucosal and visceral KS, while receiving treatment with cyclosporine,
      methotrexate, and methylprednisolone for undifferentiated arthritis. RESULTS: KS
      may result from HHV-8 infection in patients undergoing immunosuppressive
      treatment for rheumatic diseases and this is the first case of IKS occurring in
      undifferentiated arthritis. A role for immune surveillance in the pathogenesis of
      IKS is supported by the observation of disease regression following
      discontinuation of immunosuppressive therapy. In a 4-year follow-up, we showed
      that variations of the virus-specific immune responses but not of the viral load
      correlated well with the disease course, characterized by 2 remission and
      subsequent relapse phases, following changes of immunosuppressive therapy.
      CONCLUSIONS: We have provided evidence of a clear-cut correlation between changes
      in immunologic markers of HHV-8 infection and the disease course of this viral
      associated tumor, concomitant with variations of immunosuppressive treatment.
      Thus, ex vivo enzyme-linked immunospot for HHV-8-specific T-cell responses
      represents a new tool for the clinical management of rheumatic patients with IKS.

PMID- 18639318
TI  - Churg-Strauss syndrome in childhood: a systematic literature review and clinical
      comparison with adult patients.
AB  - OBJECTIVE: To describe the clinical characteristics of children with Churg
      Strauss syndrome (CSS) in comparison with adult patients. MATERIALS AND METHODS:
      A systematic literature analysis was performed in the Medline database up to
      November 2007 and in rheumatology and pulmonology meeting scientific abstracts
      2003-2007. Articles with reported childhood CSS cases were retrieved; clinical
      data were recorded. Descriptive statistical analyses and a comparison with 2
      published adult CSS cohorts were performed. RESULTS: Thirty-three cases of
      childhood CSS were identified. The mean age was 12 years and the male-to-female
      ratio was 0.74. All patients had significant eosinophilia and asthma.
      Histological evidence of eosinophilia and/or vasculitis was present in virtually
      all patients. Antineutrophil cytoplasmic antibodies were found in 25% of children
      with CSS. Initial treatment was corticosteroid monotherapy in 76% of childhood
      CSS patients, while 24% received additional immunosuppressive therapy. Another
      18% required further immunosuppression at follow-up due to frequent relapses. Six
      deaths (18%), all related to the underlying disease, occurred after a mean
      disease duration of 14 months. As compared with adult CSS patients, children had
      a predominance of cardiopulmonary disease manifestations, a lower rate of
      peripheral nerve involvement, and higher mortality. CONCLUSIONS: Many aspects of
      CSS are similar in childhood and adult patients. However, pulmonary and cardiac
      involvement is predominant in pediatric CSS and mortality is substantial.

PMID- 18639319
TI  - The natural history of bone marrow lesions in community-based middle-aged women
      without clinical knee osteoarthritis.
AB  - OBJECTIVE: Bone marrow lesions (BML) have been implicated in the pathogenesis of
      osteoarthritis, yet their exact role, etiology, and natural history remain
      unclear. The aim of this study was to examine the natural history of BML in a
      healthy population and identify risk factors associated with their persistence
      and incidence. METHODS: One hundred forty-eight healthy middle-aged women had
      magnetic resonance imaging performed on their dominant knee at baseline and 2
      years later to assess the presence, natural history, and risk factors for
      persistence and incidence of BML. RESULTS: Approximately 46% of BML present at
      baseline completely resolved over 2 years. "Large" BML had the potential to
      improve, while the majority of "very large" remained stable. In those women with
      no BML at baseline, approximately 9% developed a BML over 2 years, the majority
      in the medial compartment. There was a trend toward weight being a risk factor
      for the development of "very large" BML (P = 0.08). CONCLUSIONS: The natural
      history of BML may be different in healthy persons compared with diseased states.
      The trend for weight as a risk factor for development of a "very-large" BML
      suggests there is potential to identify modifiable risk factors for BML in
      asymptomatic people and warrants further investigation.

PMID- 18639320
TI  - Normal subtypes of the posterior part of the cerebral arterial circle in human
      fetuses.
AB  - BACKGROUND: Although centuries of the human CAC research are behind us, still
      there is a stimulus for the authors to describe something new or to add to the
      "archive" of already known facts about its angioarchitecture. METHODS: With
      normal configurations of the posterior part of the CAC in early prenatal status,
      172 brains of human fetuses from the 13th to the 24th week were used in the
      purpose of investigation. Brain arteries were injected and microdissected using a
      surgical microscope. RESULTS: According to diameter values of vascular components
      in the posterior part of the CAC, 6 basic types and the corresponding number of
      their subtypes are formed. Incidences of bilateral transitory (18.6%), fetal
      (9.3%), and adult (33.1%) types, as well bilateral asymmetric types (fetal
      transitory in 5.8%, adult-transitory in 14.5%, and adult-fetal in 18.6% of
      cases), proved that dominant configuration of posterior part had not been present
      in the period from the fourth to the sixth gestational month. CONCLUSION: The
      finding of normal subtypes of the posterior part of the CAC, as well as the
      absence of some subtypes, is a challenge for future studies of the posterior
      arterial pattern within vascular abnormalities or diseases.

PMID- 18639322
TI  - Novel biologic model for percutaneous renal surgery learning and training in the
      laboratory.
AB  - OBJECTIVES: To improve the learning and training of percutaneous renal access and
      intrarenal procedures with a biologic porcine kidney model. METHODS: We set up a
      biologic bench model using a porcine kidney. The kidney was wrapped in a full
      thickness skin flap with subcutaneous fascia and muscle and fixed to a wooden
      board with 2 long steel nails. The ureter was catheterized to inject radiologic
      contrast medium or normal saline. Percutaneous renal manipulations were then
      practiced on the model under radiographic or ultrasound guidance. RESULTS:
      Urologists with "partial" experience in advanced endourologic surgery were
      trained using this model. Of the 33 trainees practiced the percutaneous hands-on
      manipulations on this model, 20 (60.6%) attained success in performing the whole
      percutaneous procedure. One to three percutaneous access tracts were established
      successfully on each kidney practiced on. Of the 42 attendants, 36 (85.7%) rated
      this model for simulation as "very helpful" or "helpful." CONCLUSIONS: The
      porcine kidney model we developed is simple and easy to build with readily
      available materials. It provides realistic and reproducible practice for
      percutaneous renal surgery in the laboratory.

PMID- 18639323
TI  - Re: Woodruff et al.: Histologic comparison of pubovaginal sling graft materials:
      a comparative study (Urology 2008;72:85-89).

PMID- 18639324
TI  - PSA kinetics provide improved prediction of survival in metastatic hormone
      refractory prostate cancer.
AB  - OBJECTIVES: To assess the value of prostate-specific antigen (PSA) kinetics in
      predicting survival and relate this to the baseline variables in men with
      metastatic hormone-refractory prostate cancer (HRPC). METHODS: The data from 417
      men with HRPC were included in a logistic regression model that included
      hemoglobin, PSA, alkaline phosphatase, Soloway score, and performance status pain
      analgesic score at baseline. The posttreatment variables included the PSA level
      halving time after the start of treatment, PSA level at nadir, interval to nadir,
      PSA velocity (PSAV), PSA doubling time after reaching a nadir, patient age, and
      treatment. These variables were added to the baseline model, forming new logistic
      regression models that were tested for net reclassification improvement. RESULTS:
      The area under the receiver operating characteristics curve for the baseline
      model was 0.67. Of all variables related to PSA kinetics, the PSAV was the best
      predictor. The addition of PSAV to the baseline model increased the area under
      the receiver operating characteristics curve to 0.81. Only a moderate increase in
      the area under the receiver operating characteristics curve (0.83) was achieved
      by combining the baseline model in a multivariate model with PSAV, PSA doubling
      time, interval to nadir, and patient age at diagnosis of HRPC. CONCLUSIONS: The
      PSAV alone gave a better prediction of survival value than all other PSA kinetics
      variables. By combining PSAV with the variables available at baseline, a better
      ground for treatment decision-making in men with HRPC can be achieved.

PMID- 18639326
TI  - Ischemic cecal perforation secondary to ESWL of junctional stone in
      ureterosigmoidostomy (Mainz Pouch II).
AB  - We report an unusual case of ischemic cecal perforation after extracorporeal
      shock wave lithotripsy for an impacted stone at the distal end of the right
      ureter of a ureterosigmoidostomy in a 78-year-old female patient.

PMID- 18639328
TI  - Penile metastasis secondary to nasal NK/T-cell lymphoma.
AB  - We report on a case of recurrent nasal NK/T-cell lymphoma in a patient who
      presented with a penile mass. No obvious other recurrent site except the penile
      lesion was noted. Metastatic penile lymphoma is extremely rare. We describe the
      image findings and clinical course of this case.

PMID- 18639327
TI  - Tolterodine extended release is efficacious in continent and incontinent subjects
      with overactive bladder.
AB  - OBJECTIVES: To assess efficacy and tolerability of tolterodine extended release
      (ER) in continent and incontinent subjects with overactive bladder (OAB).
      METHODS: This was a post hoc analysis of data from a 12-week, double-blind,
      placebo-controlled trial of tolterodine ER (4 mg once daily). Subjects completed
      7-day bladder diaries at baseline and week 12; those with one or more
      incontinence episode(s) in their diaries at baseline were considered incontinent.
      Subjects rated urgency associated with each micturition on a scale from 1 to 5,
      and micturitions were categorized post hoc by urgency rating as non-OAB (1-2),
      OAB (3-5), or severe OAB (4-5). RESULTS: At baseline, 40% of subjects were
      incontinent. Tolterodine ER (n = 429) reduced total, OAB, and severe OAB
      micturitions compared with placebo (n = 421) in continent and incontinent
      subjects. There was no difference between continent and incontinent subjects in
      terms of the magnitude of improvement with tolterodine ER relative to placebo for
      total, OAB, and severe OAB micturitions. Reductions in mean urgency and frequency
      urgency sum ratings were significantly greater in the tolterodine ER group. Among
      incontinent subjects, tolterodine ER significantly reduced urgency urinary
      incontinence episodes and significantly increased the percentage of subjects
      achieving continence relative to placebo. Adverse event rates were low in both
      continent and incontinent subjects. CONCLUSIONS: Tolterodine ER reduced
      micturitions associated with urgency (OAB or severe OAB) in both continent and
      incontinent subjects. Tolterodine ER also reduced urgency urinary incontinence
      episodes in incontinent subjects. These data show that tolterodine ER is
      effective and well tolerated in both continent and incontinent subjects with OAB.

PMID- 18639329
TI  - Robotic radical parametrectomy and pelvic lymphadenectomy in patients with
      invasive cervical cancer.
AB  - OBJECTIVE: We describe a series of patients diagnosed with invasive cervical
      cancer after undergoing simple hysterectomy who subsequently underwent robotic
      radical parametrectomy and bilateral pelvic lymphadenectomy. The goal of this
      study is to report on the safety and feasibility of robotic radical
      parametrectomy. METHODS: A retrospective review was performed of all patients who
      underwent robotic radical parametrectomy and bilateral pelvic lymphadenectomy at
      our institution during the period December 2006 to February 2008. We analyzed our
      data to evaluate the safety and feasibility of performing robotic radical
      parametrectomy. RESULTS: This analysis included 5 patients with invasive squamous
      cell carcinoma of the cervix. The median body mass index was 23.8 kg/m(2) (range,
      17.7 to 26.5). The median operative time was 365 min (range, 331 to 430). The
      median estimated blood loss was 100 mL (range, 50 to 175). There were no
      conversions to laparotomy. There was 1 intraoperative complication--cystotomy. No
      patient required blood transfusion. The median length of hospital stay was 1 day
      (range, 1 to 2). One patient experienced two postoperative complications, a
      vesicovaginal fistula and a lymphocyst. No patient had residual tumor in the
      parametrectomy specimen, and no patient underwent adjuvant therapy. The median
      number of pelvic lymph nodes removed was 14 (range, 6 to 16). The median follow
      up for all patients was 7.5 months (range, 1.3 to 13.8). There were no
      recurrences. CONCLUSION: Robotic radical parametrectomy and bilateral pelvic
      lymphadenectomy is feasible and safe and can be performed with an acceptable
      complication rate.

PMID- 18639330
TI  - Prognostic implication of endometriosis in clear cell carcinoma of the ovary.
AB  - OBJECTIVE: The aim of this study is to investigate whether the presence of
      endometriosis is a prognostic factor in patients diagnosed with clear cell
      carcinoma (CCC) of the ovary. METHODS: Retrospective chart review was performed
      to all patients diagnosed with CCC and endometriosis between 1975 and 2002. All
      pathology reports were reviewed and slides were reviewed when available. Cox
      regression analysis and Kaplan-Meier test were used to calculate survival
      prognostic factors. The level of significance was set at 0.05. RESULTS: Eighty
      four patients with CCC were identified with a 49% rate of coexisting
      endometriosis. Patients with tumors arising in endometriosis (n=15), with
      endometriosis found elsewhere in the specimen (n=26), and those without
      endometriosis (n=43) were analyzed comparatively. Patients with CCCs arising in
      endometriosis were 10 years younger (95% C.I. 0.6-18 years) than those with CCC
      not arising in endometriosis (P<0.05). Patients with endometriosis anywhere in
      the surgical specimen presented at early stage 66% of the times versus 42% for
      patients without endometriosis (P<0.05). Median overall survival (OS) for
      patients with endometriosis was 196 months (95% C.I. 28-363) versus 34 months
      (95% C.I. 13-55) for patients without endometriosis (P=0.01). Advanced tumor
      stage at diagnosis (HR 13, 95% C.I. 5-29, P=0.001) and absence of endometriosis
      (HR 2, 95% C.I. 1-3.9, P=0.03) were the only significant prognostic factors
      associated with poor survival. Disease recurrence or death among optimally and
      completely cytoreduced patients was 31% and 59% for those with and without
      endometriosis respectively (P>0.05). CONCLUSIONS: Our study suggests that the
      presence of endometriosis in patients with CCC of the ovary is associated with
      progression free and OS advantages with no difference in initial resectability.

PMID- 18639331
TI  - Influence of seminal plasma on the kinematics of boar spermatozoa during
      freezing.
AB  - Sperm motility is, for its relation to cell viability and fertility, a central
      component of the spermiogram, where consideration of motion patterns allows
      discrimination of sub-populations among boar spermatozoa. Extension and cryo
      preservation imposes changes in these patterns in connection to handling,
      additives, temperature changes and the removal of boar seminal plasma (BSP) which
      apparently makes spermatozoa susceptible to oxidative stress, thus affecting
      survival and motility post-thaw. Detailed kinematic analyses during sperm cooling
      are sparse, particularly when considering the instrumentation and settings used
      for analyses, the effect of extenders, and of the BSP the processed spermatozoa
      are exposed to. Spermatozoa present in the first collectable 10mL of the sperm
      rich fraction of the ejaculate (portion 1, P1-BSP), have shown an increased
      ability to sustain motility during and after cryo-preservation than spermatozoa
      immersed in the rest of the ejaculate (portion 2, P2). When P2-spermatozoa were
      cleansed from their BSP and exposed for 60min to pooled P1-BSP, their motility
      post-thaw increased to similar levels as P1-spermatozoa. This BSP-influence is
      sire-dependent, presumably related to the protein concentration in the different
      ejaculate portions, and apparently unrelated to changes in membrane integrity or
      membrane stability through conventional, controlled cooling.

PMID- 18639332
TI  - The benefit of human embryonic stem cell encapsulation for prolonged feeder-free
      maintenance.
AB  - The majority of methodologies for maintaining human embryonic stem cell (hESC)
      pluripotency require the use of human or animal feeder cell layers, the most
      common being murine embryonic fibroblasts. In this study, we applied a protocol
      aimed at maintaining hESCs in culture without exposure to animal cells or
      proteins. hESCs were encapsulated in 1.1% (w/v) calcium alginate hydrogels and
      grown in basic maintenance medium for a period of up to 260 days. Investigation
      of the cell aggregates formed within the hydrogels yielded no evidence of the
      formation of any of the three germ layers, although the hESCs retained their
      pluripotency and could differentiate when they were subsequently cultured in a
      conditioned environment. Immunohistochemistry and RT-PCR showed that the hESC
      aggregates expressed protein and gene markers characteristic of pluripotency
      including Oct-4, Nanog, SSEA-4, TRA-1-60 and TRA-1-81. At the ultrastructural
      level, the cells were arranged in closely packed clusters and showed no
      cytoplasmic organelles, suggesting an undifferentiated state. These data show
      that it is possible to maintain hESCs in an undifferentiated state, without
      passaging or embryoid body formation, and without animal contamination.

PMID- 18639333
TI  - The clinical use of enriched bone marrow stem cells combined with porous beta
      tricalcium phosphate in posterior spinal fusion.
AB  - Cytotherapy for bone regeneration has not been widely used clinically. A new
      method based on enriched bone-marrow-derived mesenchymal stem cells (MSCs)
      combined with porous beta-tricalcium phosphate (beta-TCP) was used for posterior
      spinal fusion in 41 patients. The aim of the present study was to assess the
      clinical feasibility of peri-operative bone marrow stem cell enrichment and their
      combination with tricalcium phosphate. About 252 ml marrow per patient was
      harvested from bilateral iliac crest, the enriched MSCs were produced by a cell
      processor peri-operatively, then combined with porous beta-TCP granules by a
      negative pressure and a short-time incubation in the meantime of conventional
      operation, which were finally implanted back into the patient. About 45 ml
      enriched MSC suspension was collected, and 78+/-16% of MSCs were recovered. By
      enrichment technique, the number of colony-forming units which expressed alkaline
      phosphatase (CFUs-ALP+, to estimate the prevalence of MSCs) was increased 4.3
      times; the increasing folds of bone marrow nucleated cells (NCs) and MSCs had a
      positive correlation. The natural log (ln) of MSC number declined with age, and
      also, the MSC number of younger subjects (< or =40 years) was more than that of
      older ones (>40 years), but none for NCs. The number of NCs and MSCs was not
      different significantly between men and women. However, the patients with
      thoracolumbar fracture (TLF) had significantly more MSCs than those with
      degenerative disc disease (DDD), but not for NCs. On the other hand, enriched
      MSCs could adhere to the wall of porous beta-TCP within 2h combination, and
      proliferate well during culture in vitro. After 34.5 months, 95.1% cases had good
      spinal fusion results. None of the samples before grafting was positive in
      bacterial culture. Only four patients had a little exudation or moderate swelling
      in their wounds, and recovered with conservative treatment.

PMID- 18639335
TI  - Polymorphisms and haplotypes in the multidrug resistance 1 gene (MDR1/ABCB1) and
      risk of multiple myeloma.
AB  - MDR1(ABCB1) gene encodes for P-glycoprotein (P-gp, MDR1, ABCB1), an ATP-binding
      cassette superfamily member involved in the transport of xenobiotics. Here, we
      investigated whether common MDR1 single nucleotide polymorphisms (1236C>T,
      2677G>A/T and 3435C>T) affect predisposition to multiple myeloma. Genotyping was
      performed in 111 myeloma patients and 96 controls by PCR-based assays. Haplotypes
      were inferred using PHASE algorithm. We found comparable allele and genotype
      frequencies among myeloma patients and controls. Moreover, patient and control
      groups did not differ regarding MDR1 haplotype distribution (p=0.18). In
      conclusion, our results do not support major influence of MDR1 variants on the
      risk of myeloma in Caucasians.

PMID- 18639334
TI  - Localization of puff sites adjacent to the plasma membrane: functional and
      spatial characterization of Ca2+ signaling in SH-SY5Y cells utilizing membrane
      permeant caged IP3.
AB  - The Xenopus oocyte has been a favored model system in which to study spatio
      temporal mechanisms of intracellular Ca2+ dynamics, in large part because this
      giant cell facilitates intracellular injections of Ca2+ indicator dyes, buffers
      and caged compounds. However, the recent commercial availability of membrane
      permeant ester forms of caged IP3 (ci-IP3) and EGTA, now allows for facile
      loading of these compounds into smaller mammalian cells, permitting control of
      [IP3]i and cytosolic Ca2+ buffering. Here, we establish the human neuroblastoma
      SH-SY5Y cell line as an advantageous experimental system for imaging Ca2+
      signaling, and characterize IP3-mediated Ca2+ signaling mechanisms in these
      cells. Flash photo-release of increasing amounts of i-IP3 evokes Ca2+ puffs that
      transition to waves, but intracellular loading of EGTA decouples release sites,
      allowing discrete puffs to be studied over a wide range of [IP3]. Puff activity
      persists for minutes following a single photo-release, pointing to a slow rate of
      i-IP3 turnover in these cells and suggesting that repetitive Ca2+ spikes with
      periods of 20-30s are not driven by oscillations in [IP3]. Puff amplitudes are
      independent of [IP3], whereas their frequencies increase with increasing photo
      release. Puff sites in SH-SY5Y cells are not preferentially localized near the
      nucleus, but instead are concentrated close to the plasma membrane where they can
      be visualized by total internal reflection microscopy, offering the potential for
      unprecedented spatio-temporal resolution of Ca2+ puff kinetics.

PMID- 18639336
TI  - c-Kit expression in human normal and malignant stem cells prognostic and
      therapeutic implications.
AB  - The human stem cell factor/c-Kit signaling pathway is pivotal for the survival of
      embryonic, foetal and adult stem cells and for their fundamental role in
      generating healthy functioning cell and tissue types during embryonic, foetal and
      adult life. Common biological features between human stem cells and cancer cells
      include (A) self-renewal, (B) extensive capacity of proliferation, (C) migration
      to and homing at distant sites and (D) resistance to toxic agents. Given these
      shared attributes, cancer was proposed to originate from transforming mutation(s)
      in normal stem cells that dysregulate their physiological programs. This theory
      has been recently supported by the findings that among all malignant cells within
      a particular tumour, only cell fraction expressing stem cell markers such as c
      Kit named 'cancer stem cells' has the exclusive potential to generate tumour cell
      population. The involvement of c-Kit and its mutation in various haematological
      malignancies and solid tumours are reviewed. The impacts of dysregulated c-Kit as
      oncogenic tyrosine kinase on autocrine stimulation and resistance to chemotherapy
      of cancer stem cells are evaluated. The significance and efficacy of molecular
      therapeutic targeting of c-Kit signaling pathway in the management of patients
      with c-Kit-positive malignancies are appraised.

PMID- 18639337
TI  - Early renal arterial stent thrombosis associated with the JAK2 V617F mutation.

PMID- 18639338
TI  - Levels of beta 2 microglobulin have a prognostic relevance for patients with
      myelodysplastic syndrome with regard to survival and the risk of transformation
      into acute myelogenous leukemia.
AB  - We evaluated the relevance of beta 2 microglobulin (B2M) plasma concentration in
      109 patients with myelodysplastic syndrome (MDS) from the Duesseldorf registry.
      Sixty-five patients with B2M level > or =2mg/dl showed a significantly lower
      overall survival time with a median of 23 in comparison to 61 months for 44
      patients with B2M below 2mg/dl. The risk of AML evolution was higher in patients
      with B2M> or =2mg/dl. Using multivariate analysis we found the B2M level at the
      time of diagnosis to be an independent prognostic parameter for survival and for
      the risk of developing AML in high-risk MDS patients.

PMID- 18639339
TI  - Indoleamine 2,3-dioxygenase activity of acute myeloid leukemia cells can be
      measured from patients' sera by HPLC and is inducible by IFN-gamma.
AB  - The enzyme indoleamine 2,3-dioxygenase (IDO) converts tryptophan to kynurenine,
      blocking T-cell activation and inducing immunosuppression. In patients with acute
      myeloid leukemia (AML), the serum kynurenine/tryptophan ratio (Kyn/Trp) was
      raised, suggesting a higher IDO activity than in healthy people. Patients with
      higher Kyn/Trp ratios showed lower survival. IDO activity was also detected in
      AML cells after exposure to IFN-gammain vitro, suggesting that the higher Kyn/Trp
      ratio in serum of AML patients might have resulted from stimulated leukemic blast
      cells. Thus, in AML, the activity of IDO can be easily monitored, providing a
      tool for future clinical testing of IDO-blocking drugs.

PMID- 18639340
TI  - In vitro cellular drug sensitivity at diagnosis is correlated to minimal residual
      disease at end of induction therapy in childhood acute lymphoblastic leukemia.
AB  - Leukemic cells from 85 children with newly diagnosed precursor B-lineage ALL were
      tested for in vitro drug sensitivity to a panel of anti-cancer drugs. Minimal
      residual disease (MRD) was measured by RQ-PCR. There was a significant
      correlation between MRD day 29 and in vitro sensitivity to prednisolone (p<0.001)
      and doxorubicin (p=0.017), drugs administered during induction therapy. In
      patients with t(12;21) (n=20), in vitro sensitivity to doxorubicin was an
      independent factor for MRD <0.1% (p=0.031; R(2)=0.66). Thus, data show that in
      vitro drug sensitivity at diagnosis is correlated to cell kill during induction
      therapy as measured by MRD day 29.

PMID- 18639341
TI  - Indoleamine 2,3-dioxygenase is highly expressed in human adult T-cell
      leukemia/lymphoma and chemotherapy changes tryptophan catabolism in serum and
      reduced activity.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell lymphotropic
      virus type 1 (HTLV-1). Indoleamine 2,3-dioxygenase (IDO), the l-tryptophan (l
      TRP)-degrading enzyme, plays a key role in the powerful immunomodulatory effects
      of several different types of immune cells. In this study, we investigated the
      IDO expression in ATLL cells and the effect of chemotherapy on IDO-initiating l
      TRP catabolism in patients with ATLL. Serum l-kynurenine (l-KYN) concentrations,
      l-KYN/l-TRP ratio, and the level of IDO mRNA expression in ATLL cells were
      significantly increased in ATLL patients compared to those in healthy and HTLV
      positive carrier subjects. On the other hand, l-TRP level was significantly
      decreased in ATLL patients compared to that in healthy subjects. In the
      immunohistochemical staining, IDO was strongly expressed in cytoplasm of ATLL
      cells. Interestingly, serum l-KYN as well as soluble IL-2 receptor concentrations
      was significantly reduced, and l-TRP concentrations were significantly increased
      after chemotherapy. These data provide evidence that IDO is highly expressed in
      ATLL cells, and that IDO-initiating l-TRP catabolism changes with chemotherapy.

PMID- 18639342
TI  - Toxicity of bisphenol A and its bioaccumulation and removal by a marine microalga
      Stephanodiscus hantzschii.
AB  - The toxicity of bisphenol A (BPA) to Stephanodiscus hantzschii, a diatom isolated
      from tidal water of Futian Mangrove Nature Reserve, China, and the
      bioaccumulation and removal capability of the marine microalga to BPA were
      investigated in the present study. Toxicity experiments showed that the 96-h EC50
      of BPA was 8.65+/-0.26 mg/L, and the cell number and chlorophyll a content of S.
      hantzschii decreased significantly with increases in BPA at concentrations higher
      than 3.00 mg/L. S. hantzschii had high removal capability at low BPA
      concentrations as BPA was bioaccumulated and biodegraded by cells. After 16-day
      treatment, 88%, 99%, 92%, 61%, 48%, 28% and 26% of BPA were removed by the diatom
      in the media supplemented with 0.01, 0.10, 1.00, 3.00, 5.00, 7.00 and 9.00 mg/L
      BPA, respectively. The present study demonstrated that S. hantzschii was a
      tolerant isolate that could be used to remove BPA from contaminated waters.

PMID- 18639343
TI  - Cryopreservation of transfected primary dorsal root ganglia neurons.
AB  - Primary dorsal root ganglia (DRG) neurons are often used to investigate the
      relative strength of various guidance cues to promote re-growth in vitro. Current
      methods of neuron isolation are laborious and disposal of excess dissected cells
      is inefficient. Traditional immunostaining techniques are inadequate to visualize
      real-time neurite outgrowth in co-culture. Cryopreservation, in combination with
      transfection techniques, may provide a viable solution to both under-utilized
      tissue and insufficient methods of visualization. This study aims to
      qualitatively and quantitatively demonstrate successful cryopreservation of
      primary transfected and non-transfected DRG neurons. Fluorescent micrographs were
      used to assess morphology after 24h in culture and suggest similarities between
      freshly isolated neurons and neurons which have been transfected and/or
      cryopreserved. Quantitative measurements of neuron outgrowth (specifically,
      primary neurites, branch points and total neurite length) indicate that neuron
      outgrowth is not altered by cryopreservation. Transfected neurons have stunted
      outgrowth at 24h.

PMID- 18639344
TI  - Reduced Foxp3 expression with increased cytomegalovirus-specific CTL in HTLV-I
      associated myelopathy.
AB  - Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) patients show high immune responses to HTLV-I. However, it
      is unclear whether the cytotoxic T lymphocyte (CTL) responses to other chronic
      viruses also increase. We investigated the responses in the peripheral blood by
      using HLA-A*0201/peptide pentamers. The frequency of cytomegalovirus (CMV)
      specific CTL tended to be higher in HAM/TSP patients than in healthy controls
      (HCs). The frequency of CMV-specific CTL positively correlated with that of HTLV
      I Tax-specific CTL. The frequency of Foxp3+ cells in CD4+ lymphocytes tended to
      be higher in HAM/TSP patients than in ACs and HCs. The expression level of Foxp3
      was lower in HAM/TSP patients than in HCs and was inversely correlated with the
      CMV-specific CTL frequency. A percentage of Foxp3+ cells showed a positive
      correlation with the HTLV-I proviral load. These results suggest that a decrease
      in the Foxp3 expression may contribute to the high immune response to CMV and
      that the Foxp3+ regulatory T cells may play a role in the immune surveillance of
      HTLV-I.

PMID- 18639345
TI  - Effect of upper airway obstruction on pulmonary arterial pressure in children.
AB  - OBJECTIVE: Our aim was to examine the elevation of pulmonary arterial pressure in
      children with upper airway obstruction caused by adenotonsillar hypertrophy
      according to their disease severity assessed with symptom scoring and to
      demonstrate the profit for echocardiographic monitorization of the children with
      adenotonsillar hypertrophy regardless of their clinical status. METHODS: Thirty
      nine children with a diagnosis of upper airway obstruction caused by
      adenotonsillar hypertrophy were included for the study. There were 16 female and
      23 male patients. Ages of the children were between 3 and 10 years with a mean
      age of 5.78+/-1.98. Twenty children composed the control group with a similar age
      and sex distribution but without any sign and symptom of upper airway
      obstruction. Mean pulmonary arterial pressures were measured by Doppler
      echocardiography preoperatively and 6 months postoperatively. Symptom scores were
      calculated for each patient in the study group to assess their disease severity.
      The significances of changes and relations between pressure levels and symptom
      scores were calculated by statistical package for social sciences (SSPS) computer
      program in terms of Student's test, chi(2)-test and Mc Nemar's test. RESULTS:
      Mean pulmonary arterial pressure were 26.26+/-5.40 (14-36) preoperatively,
      16,61+/-2.68 (10.15-22.3) postoperatively and 16.54+/-2.63 (10.5-21.7) in the
      control group. There were a statistically significant decrease at pressure levels
      postoperatively and a significant difference from the levels in the control group
      (Student's t-test, p<0.01). We found no correlation between the pressure levels
      and disease severity assessed in terms of symptom scoring. CONCLUSION: This study
      showed that upper airway obstruction caused by adenotonsillar hypertrophy causes
      significant elevation of pulmonary arterial pressures and adenotonsilectomy is an
      absolute therapeutic method in these children. Every child with adenotonsillar
      hypertrophy has some probability of having pulmonary hypertension regardless of
      his or her disease severity. Therefore, performing echocardiographic examination
      to all children with adenotonsillar hypertrophy is beneficial for assessing the
      cardiopulmonary status of the patient and may be useful at decision making for
      adenotonsilectomy.

PMID- 18639346
TI  - Manganese effects on haematopoietic cells and circulating coelomocytes of
      Asterias rubens (Linnaeus).
AB  - Manganese (Mn) is a naturally abundant metal in marine sediments where it mainly
      occurs as MnO(2). During hypoxic conditions it is converted into a bioavailable
      state, Mn(2+), and can reach levels that previously have shown effects on immune
      competent cells of the crustacean, Nephrops norvegicus. Here we investigated if
      Mn also affects circulating coelomocytes and their renewal in the common sea
      star, Asterias rubens, when exposed to concentrations of Mn that can be found in
      nature. When the sea stars were exposed to Mn it accumulated in the coelomic
      fluid and the number of circulating coelomocytes, in contrast to what was
      recorded in Nephrops, increased significantly. By using the substitute
      nucleotide, 5-bromo-2'-deoxyuridine, BrdU, for tracing cell division and by
      recording mitotic index by nuclei staining, we found that Mn induced
      proliferation of cells from a putative haematopoietic tissue, the coelomic
      epithelium. In addition, the haematopoietic tissue and coelomocytes showed stress
      response in terms of changes in HSP70 levels and protein carbonyls, as judged by
      immunohistochemistry and Western blotting. Measurement of dehydrogenase activity,
      using MTS/PMS, revealed that Mn showed cytotoxic properties. We also found that
      the phagocytotic capacity of coelomocytes was significantly inhibited by Mn. It
      was concluded that the exposure of A. rubens to Mn induced renewal of
      coelomocytes and impaired their immune response.

PMID- 18639347
TI  - Cytotoxicities and induction of metallothionein (MT) and metal regulatory element
      (MRE)-binding transcription factor-1 (MTF-1) messenger RNA levels in the
      zebrafish (Danio rerio) ZFL and SJD cell lines after exposure to various metal
      ions.
AB  - Using zebrafish liver (ZFL) and caudal fin (SJD) cell-line models, the induction
      of metallothionein (MT) and metal regulatory element-binding transcription factor
      1 (MTF-1) mRNA levels by various metal ions (Zn(2+)(,) Cd(2+), Cu(2+), Hg(+),
      As(3+), As(5+), Cr(3+) and Cr(6+)) were studied using the real-time PCR. The
      LC(50)-24h values of the metal ions were determined for the two cell lines prior
      to their exposure to different concentrations (10%, 25%, 50%, 75% and 100% LC(50)
      values) of the heavy metal ions for RNA assay. The two cell lines were sensitive
      to As(3+), Cd(2+) and Hg(+). Zn(2+)and Cu(2+) were moderately toxic, and As(5+)
      and Cr(3+) were less toxic to both cell lines. Each of the metal ions tested was
      found to cause significant induction of the mRNA levels in the SJD cells. Only
      Zn(2+), Cd(2+), Cu(2+), Hg(2+) and As(3+) caused significant induction of MT mRNA
      levels in ZFL cells. Zn(2+)and Cd(2+) were efficient MT inducers in the two cell
      lines, but As(3+) and As(5+) are strong inducers only in the SJD cell line. In
      both cell lines, Cu(2+) and Hg(2+) are moderate inducers, and Cr(3+) and Cr(6+)
      were weak inducers of MT mRNA. MTF-1 induction is believed to be insufficient to
      cause MT gene induction, but As(3+) and Cd(2+) induced MTF-1 in ZFL cell line.
      Cd(2+) was the most efficient inducer of MT in the cell lines, and also induced
      MTF-1 levels with clear dose-responsiveness in SJD cell line. These results
      indicated that MT induction can occur without MTF-1 induction for many metal ions
      such as Zn(2+) and Cu(2+).

PMID- 18639348
TI  - Uptake and internalisation of copper by three marine microalgae: comparison of
      copper-sensitive and copper-tolerant species.
AB  - Although it has been well established that different species of marine algae have
      different sensitivities to metals, our understanding of the physiological and
      biochemical basis for these differences is limited. This study investigated
      copper adsorption and internalisation in three algal species with differing
      sensitivities to copper. The diatom Phaeodactylum tricornutum was particularly
      sensitive to copper, with a 72-h IC50 (concentration of copper to inhibit growth
      rate by 50%) of 8.0 microg Cu L(-1), compared to the green algae Tetraselmis sp.
      (72-h IC50 47 microg Cu L(-1)) and Dunaliella tertiolecta (72-h IC50 530 microg
      Cu L(-1)). At these IC50 concentrations, Tetraselmis sp. had much higher
      intracellular copper (1.97+/-0.01 x 10(-13)g Cu cell(-1)) than P. tricornutum
      (0.23+/-0.19 x 10(-13)g Cu cell(-1)) and D. tertiolecta (0.59+/-0.05 x 10(-13)g
      Cu cell(-1)), suggesting that Tetraselmis sp. effectively detoxifies copper
      within the cell. By contrast, at the same external copper concentration (50
      microg L(-1)), D. tertiolecta appears to better exclude copper than Tetraselmis
      sp. by having a slower copper internalisation rate and lower internal copper
      concentrations at equivalent extracellular concentrations. The results suggest
      that the use of internal copper concentrations and net uptake rates alone cannot
      explain differences in species-sensitivity for different algal species. Model
      prediction of copper toxicity to marine biota and understanding fundamental
      differences in species-sensitivity will require, not just an understanding of
      water quality parameters and copper-cell binding, but also further knowledge of
      cellular detoxification mechanisms.

PMID- 18639349
TI  - Ebstein's anomaly in adult.
AB  - Ebstein's anomaly is a rare congenital cardiac disease initially described by
      Wilhelm Ebstein in 1866. It is defined as the significant apical displacement of
      the part of the tricuspid valve causing significant tricuspid regurgitation and
      reduction of the functional right ventricle, right atrial and right ventricular
      dilatation and atrial and ventricular arrhythmias. Ebstein's anomaly occurs
      approximately once in 20,000 live births and only 5% of patients survive beyond
      the fifth decade. We present a case of Ebstein's anomaly in a 69-year-old Italian
      woman. Also this case is illustrative of Ebstein's anomaly in adult.

PMID- 18639350
TI  - Comments on the article by Chen-Scarabelli and Scarabelli: history of medicine in
      the 'hidden world' and relevant articles in systematic reviews.
AB  - When writing a review manuscript, choosing among potentially citable references
      is an arduous task. Decisions are commonly based on several aspects, ranging from
      obvious content relevance, passing through impact factor of the journal in which
      a prospective citable article was written, and reaching to sovereign personal
      preferences. Articles written in non-English languages or ranked in low impact
      factor journals are generally overlooked. On the other hand, articles published
      by outstanding physicians in the 'hidden world' may bear historical relevance and
      foster scientific progress.

PMID- 18639351
TI  - Long-term fish consumption is associated with lower risk of 30-day cardiovascular
      disease events in survivors from an acute coronary syndrome.
AB  - This study aimed to assess the relationship between long-term fish consumption
      and short-term prognosis of patients who had an acute coronary syndrome. The
      multi-adjusted data analysis from a total of 214 men and 79 women patients showed
      that intake of fish, n-3 and n-6 fatty acids above 7 portions, 8.8 g and 13.2 g
      per week correspondingly, is associated with 83%, 83% and 79% reduction on the
      likelihood of recurrent events in a 30-day period after hospitalisation
      hospitalization (OR=0.17, 95%CI 0.04-0.80, OR=0.17, 95%CI 0.04-0.81, OR=0.21,
      95%CI 0.05-0.97). Conclusively, an inverse relationship between long-term fish
      and fish oils consumption and short-term prognosis of patients who had had an ACS
      was observed, irrespective of various potential confounders.

PMID- 18639352
TI  - Acute myocardial infarction with diminutive right coronary artery and obstructive
      hypertrophic cardiomyopathy without significant coronary stenoses.
AB  - Focal tissue abnormalities consistent with regional ischemia have been reported
      in patients with hypertrophic cardiomyopathy (HCM). Coronary microvascular
      dysfunction has been also reported to be present in patients with HCM despite
      normal epicardial coronary arteries. Moreover, it has been demonstrated that in
      the case of HCM and idiopathic left ventricular hypertrophy, hypoplastic coronary
      arteries as diminutive vessels are present and that obstructive hypertrophic
      cardiomyopathy is associated with enhanced thrombin generation and platelet
      activation. Previously, it has been described an acute myocardial infarction in a
      young athlete with non-obstructive hypertrophic cardiomyopathy and normal
      coronary arteries. We present a case of an acute myocardial infarction with
      diminutive right coronary artery and obstructive hypertrophic cardiomyopathy
      without significant coronary stenoses. To our knowledge, this is the first report
      of an acute myocardial infarction with diminutive right coronary artery and
      obstructive hypertrophic cardiomyopathy without significant coronary stenoses.

PMID- 18639353
TI  - Insulin resistance as link between polycystic ovary syndrome and cardiovascular
      autonomic dysfunction.
AB  - Tekin et al. have shown that polycystic ovary syndrome is associated with an
      impaired autonomic neural control of the cardiovascular system, characterized by
      a depressed heart rate variability. Little is known on the mechanisms underlying
      this association. I propose insulin resistance as a possible link between
      polycystic ovary syndrome and autonomic cardiovascular function.

PMID- 18639354
TI  - Transthoracic echocardiography during sinus rhythm identifies elderly patients
      with nonvalvular paroxysmal atrial fibrillation at high risk of cerebral
      infarction.
AB  - We performed transthoracic echocardiography during sinus rhythm in elderly
      nonvalvular paroxysmal atrial fibrillation (NV-PAF) patients (> or =65 years)
      with cerebral infarction and in patients without cerebral infarction. This study
      suggests that elderly NV-PAF patients at high risk for cerebral infarction seem
      to have a pseudonormalization pattern of transmitral inflow, and decreased atrial
      reversal flow of pulmonary venous flow, and increased left atrial volume.

PMID- 18639355
TI  - A wind density model to quantify the airborne spread of Culicoides species during
      north-western Europe bluetongue epidemic, 2006.
AB  - Increased transport and trade as well as climate shifts play an important role in
      the introduction, establishment and spread of new pathogens. Arguably, the
      introduction of bluetongue virus (BTV) serotype 8 in Benelux, Germany and France
      in 2006 is such an example. After its establishment in receptive local vector and
      host populations the continued spread of such a disease in a suitable environment
      will mainly depend on movement of infected vectors and animals. In this paper we
      explore how wind models can contribute to explain the spread of BTV in a
      temperate eco-climatic setting. Based on previous work in Greece and Bulgaria
      filtered wind density maps were computed using data from the European Centre for
      Medium-Range Weather Forecasts (ECMWF). Six hourly forward wind trajectories were
      computed at pressure levels of 850 hPa for each infected farm as from the
      recorded onset of symptoms. The trajectories were filtered to remove wind events
      that do not contribute to possible spread of the vector. The suitable wind events
      were rastered and aggregated on a weekly basis to obtain weekly wind density
      maps. Next to this, cumulated wind density maps were also calculated to assess
      the overall impact of wind dispersal of vectors. A strong positive correlation
      was established between wind density data and the horizontal asymmetrical spread
      pattern of the 2006 BTV8 epidemic. It was shown that short (<5 km), medium (5-31
      km) and long (>31 km) distance spread had a different impact on disease spread.
      Computed wind densities were linked to the medium/long-distance spread whilst
      short range spread was mainly driven by active Culicoides flight. Whilst previous
      work in the Mediterranean basin showed that wind driven spread of Culicoides over
      sea occurred over distances of up to 700 km, this phenomenon was not observed
      over land. Long-distance spread over land followed a hopping pattern, i.e. with
      intermediary stops and establishment of local virus circulation clusters at
      distances of 35-85 km. Despite suitable wind densities, no long range spread was
      recorded over distances of 300-400 km. Factors preventing spread Eastwards to the
      UK and Northwards to Denmark during the 2006 epidemic are discussed. Towards the
      east both elevation and terrain roughness, causing air turbulences and drop down
      of Culicoides, were major factors restricting spread. It is concluded that the
      proposed approach opens new avenues for understanding the spread of vector-borne
      viruses in Europe. Future developments should take into consideration both
      physical and biological factors affecting spread.

PMID- 18639356
TI  - Disease and destiny-mystery and mastery.
AB  - When early people made their appearance, zoonotic infectious diseases were
      already waiting, but epidemic diseases did not appear in human history until
      people began to live in large numbers under conditions of close contact, mainly
      during the last 10,000 years. Disease has decimated urban populations, conquered
      armies, and disrupted society. The focus here is on (1) the plague of Athens and
      the Black Death; (2) smallpox, influenza, and rabies; (3) avian influenza prion
      diseases, and foot & mouth disease; and (4) emerging and re-emerging diseases.
      All have veterinary public health associations. In Athens, Greece, in 430 BC,
      when the Spartans ravaged the countryside, hordes crowded into Athens so that
      orderly movements, space in which to live, and adequate supplies of food became
      impossible. Crowding of any population fosters disease transmission; chaos and
      disorder enhance it all the more. Out of northern Egypt came a terrible plague
      from across the Mediterranean Sea. The identity of the plague of Athens remains
      unsure, but the well-considered conclusion is Rift Valley Fever, a mosquito
      borne, viral zoonosis. The Black Death, also called the Plague, raged in Asia for
      centuries. In 1347, the Black Death was brought by a ship out of Asia to Sicily.
      The scenes of devastation were repeated throughout Europe, with 90% or more of
      the people dying in city after city. Influenza, too, has been a cause of periodic
      human epidemics, but the great pandemic of influenza occurred in the last months
      of World War I. In the years of highest occurrence, more than half the world's
      population became clinically infected. If veterinary public health had been born
      earlier, it could have led to elucidating the epidemiology of influenza and the
      plagues of Athens, Europe, and Asia. In turn, smallpox had also caused continual
      tragedy. In 1796, Edward Jenner began to harvest pustules of cowpox from children
      or infected cows and inject them into susceptible children. In 1980, the World
      Health Organization declared that smallpox had been eliminated from the world.
      Rabies, though, still strikes terror. A number of animal diseases, broadly termed
      emerging and re-emerging diseases, need surveillance because they have the
      potential to impact human health. From late in 2003 to 2007, the highly
      pathogenic H5N1 influenza virus in poultry infected at least 121 people and
      caused 62 deaths in four countries. The prion diseases, too, all have very high
      numbers in concentrated contacts. To control these diseases, veterinary public
      health is essential, with diagnosis, epidemiological surveillance, clinical
      manifestations, and prevention as primary measures.

PMID- 18639357
TI  - Robustness in health research: do differences in health measures, techniques, and
      time frame matter?
AB  - Survey-based health research is in a boom phase following an increased amount of
      health spending in OECD countries and the interest in ageing. A general
      characteristic of survey-based health research is its diversity. Different
      studies are based on different health questions in different datasets; they use
      different statistical techniques; they differ in whether they approach health
      from an ordinal or cardinal perspective; and they differ in whether they measure
      short-term or long-term effects. The question in this paper is simple: do these
      differences matter for the findings? We investigate the effects of life-style
      choices (drinking, smoking, exercise) and income on six measures of health in the
      US Health and Retirement Study (HRS) between 1992 and 2002: (1) self-assessed
      general health status, (2) problems with undertaking daily tasks and chores, (3)
      mental health indicators, (4) BMI, (5) the presence of serious long-term health
      conditions, and (6) mortality. We compare ordinal models with cardinal models; we
      compare models with fixed effects to models without fixed-effects; and we compare
      short-term effects to long-term effects. We find considerable variation in the
      impact of different determinants on our chosen health outcome measures; we find
      that it matters whether ordinality or cardinality is assumed; we find substantial
      differences between estimates that account for fixed effects versus those that do
      not; and we find that short-run and long-run effects differ greatly. All this
      implies that health is an even more complicated notion than hitherto thought,
      defying generalizations from one measure to the others or one methodology to
      another.

PMID- 18639358
TI  - Auditory-motor coupling of bilateral finger tapping in children with and without
      DCD compared to adults.
AB  - The ability to modulate bilateral finger tapping in time to different frequencies
      of an auditory beat was studied. Twenty children, 7 years of age, 10 with and 10
      without developmental coordination disorder (DCD), and 10 adults tapped their
      left index and right middle fingers in an alternating pattern in time with an
      auditory signal for 15s (four trials each, randomly, at 0.8, 1.6, 2.4, 3.2 Hz per
      finger). Dominant and non-dominant finger data were collapsed since no
      differences emerged. All three groups were able to modulate their finger
      frequency across trials to closely approximate the signal frequency but children
      with DCD were unable to slow down to the lowest frequency. Children with DCD were
      more variable in tap accuracy (SD of relative phase) and between finger
      coordination than typically developing children who were respectively more
      variable than the adults. Children with DCD were unable to consistently
      synchronize their finger with the beat. Adults were tightly synchronized and
      often ahead of the beat while children without DCD tended to be behind the beat.
      Overall, these results indicated that children with DCD can only broadly match
      their finger movements to an auditory signal with variability and poor
      synchronicity as key features of their auditory-fine-motor control. Individual
      inspection of the data revealed that five children with DCD had difficulty
      matching the slowest frequencies and that these children also had higher
      variability and lower percentile MABC scores from the movement assessment battery
      for children (MABC) than other children with DCD. Three children with DCD were
      more variable only at higher frequencies and two performed like typically
      developing children.

PMID- 18639359
TI  - How trunk turns affect locomotion when you are not looking where you go.
AB  - How well do we maintain heading direction during walking while we look at objects
      beside our path by rotating our eyes, head, or trunk? Common experience indicates
      that it may be fairly hazardous not to look where you are going. In the present
      study, 12 young adults walked on a treadmill while they followed a moving dot
      along a horizontal line with their gaze by rotating primarily either their eyes,
      head, or trunk for amplitudes of up to 25 degrees . During walking the movement
      of the center of pressure (COP) was monitored using force transducers under a
      treadmill. Under normal light conditions, the participants showed little lateral
      deviation of the COP from the heading direction when they performed the eye or
      head movement task during walking, even when optic flow information was limited.
      In contrast, trunk rotations led to a doubling of the COP deviation in the
      mediolateral direction. Some of this deviation was attributed to foot rotation.
      Participants tended to point their feet in the gaze direction when making trunk
      turns. The tendency of the feet to be aligned with the trunk is likely to be due
      to a preference to have feet and body in the same orientation. Such alignment is
      weaker for the feet with respect to head position and it is absent with respect
      to eye position. It is argued that feet and trunk orientation are normally
      tightly coupled during gait and that it requires special abilities to move both
      segments independently when walking.

PMID- 18639360
TI  - Temporal and spatial control following bilateral versus unilateral training.
AB  - Principles of motor control and learning such as bilateral coordination and task
      specificity, are increasingly incorporated in the design of upper extremity
      rehabilitation protocols for stroke survivors. Yet most studies investigating the
      efficacy of new protocols report composite scores of standardized tests, such as
      the Fugl-Meyer Upper Extremity test (FM) and the Wolf Motor Arm Test, rather than
      determining how the motor control and coordination of arm movements has changed.
      Here we present a sub-study of a larger randomized controlled trial comparing a
      bilateral and unilateral training protocol where participants were assessed on
      bilateral and unilateral arm reaching. Eligible participants for the arm reaching
      analysis were 9 (FM=37) and 9 (FM=34) in Bilateral Arm Training with Rhythmic
      Auditory Cueing (BATRAC) and Dose Matched Therapeutic Exercises (DMTE),
      respectively. Participants undertook 18 sessions of training for 6 weeks with
      20min of active training per session. For bilateral arm reaching, participants
      after BATRAC were faster, with increased peak acceleration, fewer movement units,
      and smoother hand paths for each arm. The BATRAC training group showed greater
      improvements with training than the DMTE group during bilateral reaching for
      parameters of movement units and smoothness of hand path. For unilateral arm
      reaching, participants were faster after DMTE for paretic arm reaching; however,
      this group did not improve to a greater extent than the BATRAC training group.
      Within group functional gains were seen after BATRAC on FM, Wolf Motor Arm Test
      (time and weight) and after DMTE on FM and Wolf Weight. There was a positive
      correlation between movement units and the time component of the Wolf Motor Arm
      Test. The reaching analysis demonstrates task-specificity in training since
      BATRAC improves performance in bilateral reaching and DMTE improves performance
      in unilateral reaching. Temporal/spatial control outcomes in studies of post
      stroke interventions can identify functionally relevant motor control changes
      that are not captured by traditional standardized tests.

PMID- 18639361
TI  - The learning of two similar complex movement sequences: does practice insulate a
      sequence from interference?
AB  - Panzer et al. [Panzer, S., Wilde, H., & Shea, C. H. (2006). The learning of two
      similar complex movement sequences: Proactive and retroactive effects on
      learning. Journal of Motor Behavior, 38, 60-70] found evidence to indicate that
      the memory state(s) underpinning the production of a movement sequence that was
      practiced for one day was essentially "overwritten" when another similar sequence
      was subsequently practiced on the next day. An interference paradigm was used to
      determine if additional practice on the first sequence would insulate it from
      retroactive interference arising from learning a new similar sequence.
      Participants produced the sequences by moving a lever with their right arm/hand
      to sequentially presented target locations. The experimental group practiced one
      16-element movement sequence (S1) for two consecutive days. A second 16-element
      sequence (S2) was practiced on Day 3. The sequence practiced on Day 3 was created
      by switching the positions of 2 of 16 elements in the sequence practiced on the
      first day. Control groups received either two days of practice on S1 or one day
      of practice on S2. Contrary to our earlier findings (Panzer, Wilde, & Shea, 2006)
      of strong retroactive interference when S1 was only practiced for one day, we
      found no evidence of retroactive interference when S1 was practiced for two days
      prior to the switch to S2 practice. Interestingly, but also contrary to our
      earlier findings, we found the learning of S2 was facilitated by the prior
      practice of S1. This proactive facilitation was observed in S2 acquisition and on
      the S2 retention test.

PMID- 18639362
TI  - Manual asymmetries in the temporal and spatial control of aimed movements.
AB  - Right-handed participants performed aimed, left- and right-hand movements toward
      a fixed target in speed and precision conditions. The purpose was to determine
      detailed hand differences in the temporal and spatial control during the course
      of a movement. The results showed that hand differences pertaining to spatial
      control of movement direction occurred throughout movement execution, and that
      these differences were stronger in the high speed and low precision conditions.
      Furthermore, the left hand took more time to execute a movement than the right
      hand, especially in conditions of low speed and high precision. Detailed time
      analysis revealed that slowing down of the left hand specifically happened prior
      to peak acceleration and beyond peak deceleration. These detailed temporal hand
      differences reoccurred as additional discontinuities in the acceleration profile.
      These results suggest that the left hand has more difficulty at movement start
      than the right hand, possibly in overcoming initial inertia. It is discussed
      whether time-based manual asymmetries located near the end of movement execution
      should be explained in terms of increased feedback use, or should be related to
      hand differences regarding the possible active dissipation of mechanical energy
      at movement completion.

PMID- 18639363
TI  - Pioglitazone treatment stimulates circulating CD34-positive cells in type 2
      diabetes patients.
AB  - Circulating bone marrow derived immature cells, including CD34-positive (CD34(+))
      cells, contribute to maintenance of the vasculature, not only as a pool of
      endothelial progenitor cells (EPCs), but also as a source of growth/angiogenesis
      factor. We hypothesized that the thiazolidineone compound pioglitazone could
      stimulate the circulating CD34(+) cells in diabetic patients. Thirty-four
      patients with type 2 diabetes received 15-30 mg pioglitazone for 24 weeks. The
      number of circulating CD34(+) cells significantly increased at 12 and continued
      this effect for 24 weeks (1.08+/-0.39, 1.34+/-0.34 and 1.32+/-0.28cells/microl at
      0, 12 and 24 weeks, respectively). The change of CD34(+) cell levels
      (DeltaCD34(+) cells) between 0 and 12 weeks was significantly correlated with the
      change of high sensitive C reactive protein levels (Deltahs-CRP) and change in
      adiponectin levels (Deltaadiponectin) (r=-0.412, r=0.359, respectively). Our
      study demonstrated that pioglitazone treatment increased circulating CD34(+)
      cells, suggesting that this effect may at least partly contribute to the anti
      atherosclerotic action of pioglitazone.

PMID- 18639364
TI  - Willingness-to-pay stated preferences for 8 health-related quality-of-life
      domains in psoriasis: a pilot study.
AB  - BACKGROUND: Psoriasis is a chronic skin condition that has a major impact on
      health-related quality of life (QOL). We evaluated health-related QOL via
      willingness to pay and a ranking task for 8 domains of health relevant to
      psoriasis: intimacy, physical comfort, self-care, ability to work or volunteer,
      ability to concentrate, emotional health, social comfort, and ability to sleep.
      OBJECTIVE: The goals of the study were to pilot test a new method to measure QOL
      impact in psoriasis and identify the areas of life most affected by psoriasis.
      METHODS: Forty participants with a history of psoriasis were interviewed in a
      face-to-face format. First, participants were asked to rank the 8 domains of
      health we were investigating. Second, patients were asked how much money they
      would be willing to pay for a hypothetical cure for each domain of health.
      Responses in US dollars were interpreted as strength of preference rather than
      absolute monetary values. RESULTS: About half of the patients in the sample (48%)
      were female, 60% had a college degree or further education, and 38% had an income
      level over $45,000/y. Physical comfort, social comfort, and emotional health were
      highly ranked by more than 75% of respondents. Ability to concentrate was least
      likely to be affected by psoriasis with just a quarter (25.7%) of respondents
      ranking this domain as important. The median amount patients were willing to pay
      for a hypothetical cure of psoriasis specific to a particular domain was highest
      for physical comfort ($2000, 25th quartile = $500, 75th quartile = $5500) and
      emotional health ($2000, 25th quartile = $250, 75th quartile = $5000), and lowest
      for ability to sleep ($625, 25th quartile = $50, 75th quartile = $5000).
      LIMITATIONS: The sample size is modest for this pilot study. Willingness to pay
      as a method of eliciting stated preferences for qualitative aspects of health may
      be influenced by individual perception of money. CONCLUSIONS: This study
      successfully pilot tested a willingness-to-pay method and a ranking task to
      measure the relative severity of 8 domains of health-related QOL and found that
      physical comfort, social comfort, and emotional health were the domains of health
      most affected by psoriasis.

PMID- 18639365
TI  - Altered connectivity among emotion-related brain regions during short-term memory
      in Alzheimer's disease.
AB  - A PET study of patients with Alzheimer's disease (AD) engaged in a delayed match
      to-sample face recognition task revealed that performance declines as a function
      of increasing delay, a pattern accompanied by reduced functional connectivity of
      prefrontal cortex but increased connectivity of the left amygdala. Here, we
      characterize the changes in interactions within this amygdalar circuit across the
      memory delays using structural equation modeling. The magnitude of effective
      connections was found to be much greater in the patients than in the controls,
      notably from the left amygdala to left inferior prefrontal cortex, which, in
      turn, influenced its right homologue. The influence from the amygdala to the left
      hippocampus, in contrast, was not strong in either group. We interpret this
      pattern of interactions as possibly reflecting the compensatory recruitment of a
      dynamic neural network, perhaps involved in implicit emotional processing, in the
      context of a faulty executive maintenance and retrieval system.

PMID- 18639366
TI  - Synergistic anti-Parkinsonism activity of high doses of B vitamins in a chronic
      cellular model.
AB  - We propose that elevation of mitochondrial enzyme cofactors may prevent or
      ameliorate neurodegenerative diseases by improving mitochondrial function. In the
      present study, we investigated the effects of high doses of B vitamins, the
      precursors of mitochondrial enzyme cofactors, on mitochondrial dysfunction,
      oxidative stress, and Parkinsonism in a 4-week long rotenone treatment-induced
      cellular model of Parkinson's disease (PD). Pretreatment with B vitamins (also 4
      weeks) prevented rotenone-induced: (1) mitochondrial dysfunction, including
      reduced mitochondrial membrane potential and activities of complex I; (2)
      oxidative stress, including increase in reactive oxygen species, oxidative DNA
      damage and protein oxidation, and (3) Parkinsonism parameters, including
      accumulation of alpha-synuclein and poly-ubiquitin. The optimum doses were found
      around 2.5- and 5-fold of that in normal MEM medium. The 4-week pretreatment was
      chosen based on time-dependent experiments that pretreatments longer than 2 weeks
      resulted in a decrease in oxidants, an increase in oxygen consumption, and up
      regulation of complex I activity and PGC-1alpha expression. Individual B vitamins
      at the same doses did not show a similar effect suggesting that these B vitamins
      work synergistically. These results suggest that administration of high doses of
      B vitamins sufficient to elevate mitochondrial enzyme cofactors may be effective
      in preventing PD by reducing oxidative stress and improving mitochondrial
      function.

PMID- 18639367
TI  - The PPAR-gamma Pro12Ala polymorphism and risk of cognitive impairment in a
      longitudinal study.
AB  - The Pro12Ala polymorphism in the PPAR-gamma gene has been associated with reduced
      incidence of type 2 diabetes. Although diabetes has been implicated as a risk
      factor for dementia, the association of Pro12Ala with cognitive impairment is
      unclear. Dementia and cognitive impairment without dementia (CIND) were
      determined during six annual follow-up evaluations in a cohort of 929 older
      Latinos. Among those with diabetes at baseline, there was an increased rate of
      dementia/CIND for Ala carriers compared to non-carriers (adjusted hazard ratio
      (HR)=2.5, 95% confidence interval (CI): 1.3-4.9) but not among non-diabetic
      participants (adjusted HR=0.94; 95% CI: 0.49-1.8). Among males, there was also an
      increased rate for Ala carriers (adjusted HR=2.7, 95% CI: 1.4-5.2) but not among
      female carriers (adjusted HR=0.88; 95% CI: 0.47-1.6). The rate of dementia/CIND
      was highest in diabetic male Ala carriers (adjusted HR=4.2; 95% CI: 1.5-11)
      compared to non-diabetic male carriers (adjusted HR=2.9; 95% CI: 1.1-7.4),
      diabetic female carriers (HR=1.6; 95% CI: 0.66-4.1), and non-diabetic female
      carriers (HR=0.52; 95% CI: 0.21-1.3). These data suggest that although the Ala
      variant is associated with a reduced risk of type 2 diabetes, it may increase the
      risk of cognitive impairment in individuals once diabetes has developed. Male Ala
      carriers may also have a greater risk of dementia/CIND.

PMID- 18639368
TI  - A pyrazole derivative of curcumin enhances memory.
AB  - Reduced cognitive function is associated with Alzheimer's and Parkinson's
      diseases as well as brain trauma and ischemia. However, there are few compounds
      that enhance memory and are also orally active. We recently synthesized a
      pyrazole derivative of curcumin called CNB-001 that enhances the activity of
      Ca(2+)/calmodulin dependent protein kinase II (CaMKII). Since CaMKII plays a
      central role in long-term potentiation (LTP) and memory, it was asked if CNB-001
      can facilitate the induction of LTP in rat hippocampal slices and enhance memory
      in a rat object recognition test. It is shown that CNB-001 enhances both LTP and
      memory.

PMID- 18639369
TI  - 1,5-Benzothiazepine, a versatile pharmacophore: a review.
AB  - 1,5-Benzothiazepine and 1,5-benzodiazipine are the two main seven-membered
      heterocyclic ring systems reported for their cardiac and psychotherapeutic
      activities. Successful introduction of diltiazem and clentiazem for angina
      pectoris, hypertension, arrhythmias and other related cardiac disorders proved
      potential of 1,5-benzothiazepine moiety. Subsequently 1,5-benzodiazepines were
      highlighted as important biologically active scaffolds. Also, discovery of
      thiazesim and quetiapine fumarate as psychotropic agents attracted much attention
      worldwide. The current review article focuses on pharmacological profile
      associated with 1,5-benzodiazepines. This article mainly covers structural
      modifications done for various targets along with the brief description of the
      targets.

PMID- 18639370
TI  - Provenance of unknown plutonium material.
AB  - The determination of the provenance of 'unknown' plutonium material is
      demonstrated through a simulation study based on an isotopic fingerprinting
      approach. Plutonium of known provenance was considered as the 'unknown' nuclear
      material in order to evaluate the potential of the approach and verify its
      predictive capabilities. Factor analysis was used to compare the Pu isotopic
      composition of the 'unknown' material with Pu isotopic compositions simulating
      well known spent fuels from a range of commercial nuclear power stations. The
      provenance of the 'unknown material' is assigned to the commercial fuel with
      which exhibits the highest degree of similarity with respect to the Pu
      composition. The approach appears promising since it accurately predicted the
      provenance of the one 'unknown' sample considered; nevertheless, the approach is
      still at the development stage. Important challenging issues related to the
      simulation uncertainties and its testing on real laboratory samples have to be
      explored prior to evaluating the potential of the approach.

PMID- 18639371
TI  - Consequence of therapy discontinuation in bisphosphonate-associated osteonecrosis
      of the jaws.
AB  - We report a patient with bisphosphonate-associated osteonecrosis of the jaws who
      developed pathological fractures of the upper and lower extremities after the
      suspension of treatment with bisphosphonates. Temporary discontinuation of the
      drugs does not alter the clinical course of the disease, and could result in the
      recurrence of bone pain and the progression of metastases or osteolytic lesions.

PMID- 18639372
TI  - Lateralization of visuospatial attention across face regions varies with
      emotional prosody.
AB  - It is well-established that linguistic processing is primarily a left-hemisphere
      activity, while emotional prosody processing is lateralized to the right
      hemisphere. Does attention, directed at different regions of the talker's face,
      reflect this pattern of lateralization? We investigated visuospatial attention
      across a talker's face with a dual-task paradigm, using dot detection and
      language comprehension measures. A static image of a talker was shown while
      participants listened to speeches spoken in two prosodic formats, emotional or
      neutral. A single dot was superimposed on the speaker's face in one of 4 facial
      regions on half of the trials. Dot detection effects depended on emotion
      condition--in the neutral condition, discriminability was greater for the right-,
      than for the left-, side of the face image, and at the mouth, compared to the eye
      region. The opposite effects occurred in the emotional prosody condition. The
      results support a model wherein visuospatial attention used during language
      comprehension is directed by the left hemisphere given neutral emotional prosody,
      and by the right hemisphere given primarily negative emotional prosodic cues.

PMID- 18639373
TI  - Response of spinach (Spinacea oleracea) to the added fluoride in an alkaline
      soil.
AB  - The influence of soil contamination by inorganic fluoride (NaF) on the uptake and
      accumulation of fluoride in the shoot and root of spinach (Spinacea oleracea) was
      investigated in pot experiment under controlled conditions. The soluble fluoride
      in soil varied between 2.57 mgkg(-1) soil and 16.44 mgkg(-1) soil in the
      treatment range of 0-800 mgNaF kg(-1) soil. It was found that the concentration
      of the total fluoride in shoot and root varied between 23.5 mgkg(-1) dry wt.
      (control) and 219.8 mgkg(-1) dry wt. (at 800 mgNaF kg(-1) soil). The fluoride
      concentration in shoot and root showed a linear trend. At the added fluoride
      concentration beyond 200 mgNaF kg(-1) of soil, the spinach root retained more
      fluoride than shoot. In the treatment range 0-800 mgNaF kg(-1) soil, the water
      labile fluoride in the juice varied from 0.32 to 0.78 ppm in shoot and 1.03 to
      2.79 ppm in the root. No visible symptom of phyto-toxicity was noticed with the
      treatment from 0 to 800 mgNaF kg(-1) soil. It was inferred from this study that
      spinach (S. oleracea) accumulates fluoride at tissues level and has a distinct
      mechanism of partitioning of water labile fluoride and total fluoride in the
      tissues.

PMID- 18639374
TI  - The attitudes of Japanese high school students toward cardiopulmonary
      resuscitation.
AB  - BACKGROUND AND OBJECTIVES: It is essential to have a clear understanding of the
      present condition of cardiopulmonary resuscitation (CPR) training courses and the
      associated problems. The present study was performed to identify the current
      conditions of CPR training in Japanese high schools and the attitudes of students
      toward CPR. METHODS AND RESULTS: We distributed a questionnaire study to the
      students of 12 cooperating high schools regarding their willingness to perform
      CPR in 5 hypothetical scenarios of cardiopulmonary arrest: a stranger, a trauma
      patient, a child, an elderly person, and a relative. Between February and March
      2006, a total of 3316 questionnaires were completed. Across all scenarios, only
      27% of respondents from general high schools reported willingness to perform
      chest compression (CC) plus mouth-to-mouth ventilation (MMV), and 31% reported
      willingness to perform CC alone. Fifty-nine percent of students had previous CPR
      training, and only 35% were willing to perform CC plus MMV. Most of the
      respondents who reported that they would decline to perform full CPR, stated that
      poor knowledge and/or fear of incomplete performance of CPR were deciding
      factors. CONCLUSIONS: Japanese high school students are reluctant to perform CC
      plus MMV, despite having received training. The present educational system in
      Japan has limitations in encouraging high school students to perform CC plus MMV.

PMID- 18639375
TI  - The autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) induces
      senescence or quiescence of prostate, breast and liver cancer cells via
      transcriptional activation of p53.
AB  - Tumor suppressive actions of the autocrine human secreted PDZ domain-containing
      protein 2 (sPDZD2) have been reported, but the mechanisms remain enigmatic. Here,
      we showed that sPDZD2 induced senescence of prostate cancer DU145 cells,
      quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via
      transcriptional activation of mutant or wild-type p53. Furthermore, sPDZD2
      sensitized mutant p53-positive DU145 cells and wild-type p53-positive MCF-7 cells
      to apoptosis induction through genotoxic stress imposed by sub-lethal
      concentration of hydrogen peroxide. Together, our findings suggest a potential
      autocrine pathway of p53 activation by transcriptional regulation, and a new
      approach to reactivate p53 for cancer therapy.

PMID- 18639376
TI  - MicroRNAs in the pathogenesis of neuroblastoma.
AB  - MicroRNAs constitute a family of small RNA species that regulate translation and
      stability of mRNA. This additional layer of epigenetic regulation has escaped
      discovery until recently, and introduces another level between mRNA expression
      profiling and proteomics. Since microRNAs are involved in regulating most, if not
      all cellular processes, their involvement in oncogenesis was anticipated. Indeed,
      soon after their discovery, microRNAs were found to act as tumor suppressor genes
      by blocking the translation of oncogenes and act as oncogenes by inhibiting the
      translation of tumor suppressor genes. Here we review the most recent attempts
      aiming to analyze the functional roles of microRNAs in neuroblastoma, the most
      devastating solid tumor in childhood.

PMID- 18639377
TI  - Application of statistical experimental methodology to optimize reactive dye
      decolourization by commercial laccase.
AB  - Three-level Box-Behnken factorial design with three factors (pH, temperature and
      enzyme concentration) combined with response surface methodology (RSM) was
      applied to optimize the dye degradation of reactive red 239 (RR239), reactive
      yellow 15 (RY15) and reactive blue 114 (RB114) dyes by commercial laccase.
      Mathematical models were developed for each dye showing the effect of each factor
      and their interactions on colour removal. The model predicted for RY15 that a
      decolourization above 90% (after 24h) could be obtained when the enzyme
      concentration, temperature and pH were set at 109.8U/L, 39.2 degrees C and 6.6,
      respectively; whilst for RB114 and RR239 the temperature and enzyme concentration
      did not affect the decolourization (>90%) in the considered range and optimum pH
      value was found at 5.5-7.0 and 7.0-7.5, respectively. These predicted values were
      also experimentally validated. Average final values of responses were in good
      agreement with calculated values, thus confirming the reliability of the models
      of RY15, RB114 and RR239 decolourization.

PMID- 18639378
TI  - Hydroxylamine nitrate self-catalytic kinetics study with adiabatic calorimetry.
AB  - Hydroxylamine nitrate (HAN) is an important member of the hydroxylamine compound
      family with applications that include equipment decontamination in the nuclear
      industry and aqueous or solid propellants. Due to its instability and
      autocatalytic behavior, HAN has been involved in several incidents at the Hanford
      and Savannah River Site (SRS) [Technical Report on Hydroxylamine Nitrate, US
      Department of Energy, 1998]. Much research has been conducted on HAN in different
      areas, such as combustion mechanism, decomposition mechanism, and runaway
      behavior. However, the autocatalytic decomposition behavior of HAN at runaway
      stage has not been fully addressed due to its highly exothermic and rapid
      decomposition behavior. This work is focused on extracting HAN autocatalytic
      kinetics and analyzing HAN critical behavior from adiabatic calorimetry
      measurements. A lumped autocatalytic kinetic model for HAN and associated model
      parameters are determined. Also the storage and handling critical conditions of
      diluted HAN solution without metal presence are quantified.

PMID- 18639379
TI  - Confirming Pseudomonas putida as a reliable bioassay for demonstrating
      biocompatibility enhancement by solar photo-oxidative processes of a
      biorecalcitrant effluent.
AB  - Experiments based on Vibrio fischeri, activated sludge and Pseudomonas putida
      have been employed to check variation in the biocompatibility of an aqueous
      solution of a commercial pesticide, along solar photo-oxidative process (TiO(2)
      and Fenton reagent). Activated sludge-based experiments have demonstrated a
      complete detoxification of the solution, although important toxicity is still
      detected according to the more sensitive V. fischeri assays. In parallel, the
      biodegradability of organic matter is strongly enhanced, with BOD(5)/COD ratio
      above 0.8. Bioassays run with P. putida have given similar trends, remarking the
      convenience of using P. putida culture as a reliable and reproducible method for
      assessing both toxicity and biodegradability, as a substitute to other more time
      consuming methods.

PMID- 18639380
TI  - Effect of sertindole on QTc interval in patients with schizophrenia.
AB  - Sertindole has been marketed and offered daily clinical practice only for 9
      months in our country, so no data has been its QTc prolongation potential. In the
      present study, we performed a clinical trial to investigate the effects of
      sertindole on QTc in patients with schizophrenia. The study comprised 21 patients
      with schizophrenia. Sertindole was administered in the following dosing regime:
      treatment was initiated with 4 mg/day sertindole. From day 3 to day 6, the dose
      was increased to 8 mg/day, and up to day 9, it was raised to 12 mg/day. The
      protocol allowed up to dose of 20mg/day according to effectiveness and
      tolerability. QTc values were determined at beginning, months 3 and 6. In
      addition, Positive and Negative Syndrome Scale (PANSS) were scored concomitantly.
      At the beginning of 6-month period, the mean QTc interval of patients was 391.7+/
      19.2 ms. At the end of this period, it was 402.8+/-23.8 ms. Although the mean QTc
      interval changing was significant throughout 6-month period, of the patients, at
      any evaluation point, only 1 female (451 ms) and 1 male (433 ms) had borderline
      prolongation at month 3 for both, without any exceeding the dangerous limits. In
      summary, our results suggest that sertindole is tolerable and despite dose
      related QT prolongation, sertindole had not the proarrhythmic profile. Future
      studies with larger sample evaluating the effects of treatment are required.

PMID- 18639381
TI  - Three-dimensional imaging in double aberration-corrected scanning confocal
      electron microscopy, part I: elastic scattering.
AB  - A transmission electron microscope fitted with both pre-specimen and post
      specimen spherical aberration correctors enables the possibility of aberration
      corrected scanning confocal electron microscopy. Imaging modes available in this
      configuration can make use of either elastically or inelastically scattered
      electrons. In this paper we consider image contrast for elastically scattered
      electrons. It is shown that there is no linear phase contrast in the confocal
      condition, leading to very low contrast for a single atom. Multislice simulations
      of a thicker crystalline sample show that sample vertical location and thickness
      can be accurately determined. However, buried impurity layers do not give strong,
      nor readily interpretable contrast. The accompanying paper examines the detection
      of inelastically scattered electrons in the confocal geometry.

PMID- 18639382
TI  - Pen studies on the control of cattle tick (Rhipicephalus (Boophilus) microplus)
      with Metarhizium anisopliae (Sorokin).
AB  - Three field trials were conducted over 12 months to assess the pathogenicity of
      Metarhizium anisopliae to parasitic stages of Rhipicephalus (Boophilus) microplus
      on dairy heifers under different environmental conditions. Two isolates were
      selected based on their high optimal growth temperature (30 degrees C), good
      spore production characteristics and ability to quickly kill adult engorged ticks
      in the laboratory. Spores were formulated in an oil emulsion and applied using a
      motor driven spray unit. Surface temperatures of selected animals were monitored,
      as were the ambient temperature and relative humidity. Unengorged ticks sampled
      from each animal immediately after treatment were incubated in the laboratory to
      assess the efficacy of the formulation and application. Egg production by
      engorged ticks collected in the first 3 days after treatment was monitored. Side
      counts of standard adult female ticks were conducted daily, before and after
      treatment to assess the performance of the fungus against all tick stages on the
      animals. In each trial the formulation rapidly caused 100% mortality in
      unengorged ticks that were removed from cattle and cultured in the laboratory. A
      significant reduction in egg production was recorded for engorged ticks collected
      in the 3 days post-treatment. However, there was little effect of the formulation
      on the survival of ticks on cattle, indicating that there is an interaction
      between the environment of the ticks on the cattle and the biopesticide, which
      reduces its efficacy against ticks.

PMID- 18639383
TI  - Intestinal parasitism in the animals of the zoological garden "Pena Escrita"
      (Almunecar, Spain).
AB  - Gastrointestinal parasites cause serious diarrhoea in captive animals. Therefore,
      we have undertaken this study to establish programmes to prevent, control, and
      treat intestinal parasitism in the animals of the zoological garden "Pena
      Escrita" of Almunecar (Granada). An annual survey was conduced to estimate the
      occurrence of gastrointestinal parasites and the seasonality of this parasitism.
      Between June 2006 and May 2007, 432 samples were collected from primates,
      carnivores, perissoodactyla, artiodactyla, rodentia, diprotodontia, galliformes,
      anseriformes and struthioniformes. One or more intestinal parasites were
      identified in 72.5% of the animals. The most frequent pathogenic endoparasites
      were Eimeria spp. (17.3%), Trichuris spp. (5.1%), Strongyloides spp. (4.5%),
      Cyclospora spp. (4.5%), Cryptosporidium spp. (3.2%) and Isospora spp. (2.6%).
      Iodamoeba butschlii, Parascaris equorum and Trichuris spp. did not vary with
      season and Cryptosporidium spp., Dicrocoelium dendriticum, Metastrongylus spp.
      and Cylicospirura spp. appeared exclusively in Artiodactyla. Multiple parasitic
      infections were common, 70% of animals presented with at least two parasites
      (maximum=6). The most frequent cases of multiple parasitism were Eimeria spp.
      plus Blastocystis spp. and Eimeria spp. plus Nematodirus spp., in the last case
      the animals presented explosive diarrhoea. In accord with our results, after each
      sampling, some of the affected animals were treated and the corresponding
      programmes of prevention and control were designed.

PMID- 18639384
TI  - Are all negative consequences truly negative? Assessing variations among college
      students' perceptions of alcohol related consequences.
AB  - Brief feedback sessions have been shown to reduce alcohol consumption in college
      student samples. However, these feedback sessions show mixed results in reducing
      negative consequences of alcohol consumption. Because the discussion of alcohol
      consequences is a component of feedback sessions, it was seen as important to
      evaluate the degree to which college students perceive these consequences as
      negative. The present study assessed college students' perceptions of positivity
      negativity of alcohol related consequences they experienced during the past year.
      The findings revealed college students' perceptions of positivity-negativity
      varied depending on the consequence that was assessed. Most consequences were
      considered negative by greater than 50% of the sample. There were six
      consequences that were not considered negative by the majority of the sample and
      of these, all were considered positive or neutral by greater than at least 50% of
      the sample. Finally, perceived positivity of the consequences were associated
      with higher weekly drinking patterns for vomiting, blackouts, regretted sex, late
      to work/class, skipping an evening meal, and being hungover. Results are
      discussed in reference to improving brief alcohol interventions for college
      students.

PMID- 18639385
TI  - The potential utility of indomethacin in enhancing the pediculocidal activity of
      permethrin, pyrethrins, and DDT.

PMID- 18639386
TI  - Maternal smoking as a cause of mosaic aneuploidy in spontaneous abortions.

PMID- 18639387
TI  - Endothelial VE-cadherin expression in human lungs.
AB  - Cell adhesion molecule vascular endothelial cadherin (VE-cadherin) is the major
      component of endothelial adherence junctions, maintaining endothelial cell
      integrity. Studies dealing with constitutive VE-cadherin expression patterns in
      different pulmonary vessel types (arteries, arterioles, capillaries, venules,
      veins) or with the influence of physiological factors such as age or sex on VE
      cadherin expression have not been published yet. Knowledge of constitutive resp.
      varying expression patterns not only fundamentally contribute to understanding
      the role of VE-cadherin in the pathogenesis of pulmonary diseases but also help
      to develop therapies based on immunotargeting. Hence, endothelial VE-cadherin
      expression was studied in regular lung tissue. Fifty-eight specimens of regular
      lung tissue (30 females, 28 males between 1 month and 75 years old) were
      immunohistochemically stained with an antibody against VE-cadherin. There was
      strong endothelial expression of VE-cadherin in arteries, arterioles, and
      capillaries but almost no expression in veins and venules. Neither age nor sex
      had any influence on the expression pattern or staining intensity. There is a
      vessel type-specific expression pattern for VE-cadherin in regular human lung
      tissue, which is not influenced by age or sex. Further studies will have to prove
      whether this is influenced by pathological conditions, e.g., ARDS.

PMID- 18639388
TI  - Tobacco smoking and risk of recurrence for squamous cell cancer of the anus.
AB  - OBJECTIVE: Squamous cell cancer of the anus is associated with multiple risk
      factors, including infection with human papillomavirus, immunosuppression,
      chronic inflammation, and tobacco smoking, although there is little data on these
      factors for the prediction of recurrent disease. Here, we evaluated the risk of
      recurrence and mortality of anal carcinoma in association with tobacco smoking.
      METHODS: We conducted a retrospective review of cases of anal carcinoma from two
      local hospitals. We obtained information on treatment response and cancer
      recurrence, as well as tobacco usage from medical records. RESULTS: We identified
      64 patients with squamous cell cancer of the anus, and 34 of these (53%) had a
      tobacco smoking history. Current smokers had higher carcinoma recurrence rates
      (11/34, 32%) than non-smokers (6/30, 20%). Overall mortality was 33% (21/64), and
      cancer-related mortality was 23% (15/64). Smokers were more likely to die from
      recurrence than non-smokers, with 45% of smokers dead compared to only 20% of non
      smokers by 5 years after treatment. CONCLUSION: Tobacco smoking appears to be
      associated with anal carcinoma disease recurrence, and is related to increased
      mortality. This data suggests that patients should be cautioned about tobacco
      smoking once a diagnosis of anal carcinoma is made in attempt to improve their
      long-term outcome.

PMID- 18639389
TI  - Biomarkers associated with breast cancer are associated with obesity.
AB  - BACKGROUND: Obesity is linked to the development of postmenopausal breast cancer,
      and some studies indicate obesity predicts a worse prognosis for premenopausal
      women who develop the disease. It was our hypothesis that proteins associated
      with breast cancer would be associated with body mass index (BMI). METHODS: We
      searched our database of women enrolled in breast health translational research
      trials for information on BMI and markers predictive of breast cancer (basic
      fibroblast growth factor (bFGF), prostate-specific antigen (PSA), human
      kallikrein (hK)2, and urinary plasminogen activator (uPA). Information on BMI and
      one or more nipple aspirate fluid (NAF) or serum biomarkers was available from
      382 women. RESULTS: In this data set, NAF and serum levels of PSA (nPSA and
      sPSA), and NAF levels hK2, bFGF and uPA were each associated with pre- and/or
      postmenopausal breast cancer. sPSA was inversely associated with BMI in both pre-
      (r=-.56, p=.001) and postmenopausal women (r=-.62, p=.0035) without breast
      cancer. This association was lost when controlling for plasma volume. In women
      without breast cancer, NAF bFGF (p=.07, premenopausal subjects) and NAF hK2
      (p=.09, postmenopausal subjects) were borderline associated with BMI. In women
      with breast cancer, nPSA was inversely (r=-.53, p=.049) associated with BMI in
      premenopausal women and directly associated with BMI in postmenopausal women
      (r=.37, p=.017). nPSA trended higher in hormone sensitive cancers, especially
      those that expressed progesterone receptor (p=.059). CONCLUSIONS: sPSA was
      inversely associated with BMI in all pre- and postmenopausal women and
      specifically in pre- and postmenopausal women without breast cancer. NAF PSA was
      associated with BMI in pre- and postmenopausal women with breast cancer.
      Evaluating the change in PSA with changes in weight may provide clues regarding a
      subject's breast cancer risk.

PMID- 18639391
TI  - Self-injurious behaviour, traumatic life events and alexithymia among treatment
      seeking opiate addicts: prevalence, pattern and correlates.
AB  - OBJECTIVE: Aim of this study was to determine the prevalence and pattern of self
      injurious behaviour (SIB) and identify the predictors of SIB among treatment
      seeking opiate addicts. METHODS: Participants were 80 consecutively consenting
      opiate addicts admitted into community and inpatient treatment programmes of a
      large South London National Health Service (NHS) Mental Health Trust. Substance
      dependence was diagnosed with ICD-10. The following instruments were
      administered: self-injurious behaviour questionnaire, traumatic life events
      questionnaire, Toronto alexithymia scale and substance abuse assessment
      questionnaire. RESULTS: Lifetime SIB prevalence rate was 49% (95% CI=37-60).
      There was no difference in lifetime SIB rates of male (50%) and female (46%)
      patients. The predominate function of SIB among opiate addicts was affect
      regulation followed by self-punishment. Using a logistic regression, sexual
      harassment and difficulty identifying feelings were the only independent
      significant predictors of SIB, with the influence of age of first traumatic event
      and gender partialled out. CONCLUSION: Given these findings, there is strong
      evidence to suggest that treatment of opiate addiction should involve routine
      screening for adult sexual trauma, deficits in emotional regulation and SIB.
      Where these problems are identified, appropriate psychological intervention
      should be integral to routine care for affected patients.

PMID- 18639390
TI  - Trends in prevalence of prognostic factors and survival in lung cancer patients
      from 1985 to 2004 at a tertiary care center.
AB  - BACKGROUND: After a prolonged period of increasing rates of lung cancer incidence
      and mortality for both men and women, incidence and mortality rates are
      decreasing in men and stabilizing in women. The goal of this study was to assess
      changes over 20 years in the prevalence of known risk factors for lung cancer and
      to elucidate possible predictors associated with lung cancer survival. METHODS:
      The study included a total of 908 patients with primary lung cancer referred to
      The University of Texas M.D. Anderson Cancer Center over three study periods 1985
      1989 (N=392), 1993-1997 (N=216), and 2000-2004 (N=300). Detailed questionnaires
      were used to collect information from the patients. Hazard ratios were estimated
      by fitting a Cox proportional hazards model. Using the Kaplan-Meier method,
      survival in months was calculated up to 2 years from the date of diagnosis to
      achieve comparability in the three groups. RESULTS: We observed a decrease in the
      proportion of patients who are current cigarette smokers and an increase in the
      proportion of patients who present with adenocarcinoma of the lung, are obese and
      patients who present with localized disease. We also found an increase in the
      number of patients who report a family history of lung cancer. The overall median
      survival duration has increased over the years from 12.0 months in 1985-1989 to
      17.5 months in 2000-2004. Also, the probability of survival of patients who were
      alive at 2 years after diagnosis has also increased (26.5% in 1985-1989 to 40.8%
      in 2000-2004). Overall, women had a better median survival than men. CONCLUSIONS:
      The results show that the demographic, histologic, clinical, and outcome
      variables of patients with lung cancer have changed over the past 20 years. Most
      important, the survival of patients with lung cancer has improved.

PMID- 18639392
TI  - The developmental origin of adolescent alcohol use: findings from the Mater
      University Study of Pregnancy and its outcomes.
AB  - BACKGROUND: It is unclear whether fetal alcohol exposure contributes to alcohol
      use in adolescence. In this study, we examine the association between maternal
      alcohol use in pregnancy and adolescents' drinking patterns at age 14. METHODS:
      The association of maternal alcohol exposure with early drinking was examined in
      4363 adolescents taking part to the Mater University Study of Pregnancy (MUSP)
      and its outcomes, a population based birth cohort study commenced in Brisbane
      (Australia) in 1981. Mothers and children were followed up at birth, 5 and 14
      years after the initial interview. Maternal alcohol use was assessed before and
      during pregnancy and at the 5 years follow-up. Adolescents' alcohol use was
      assessed at child age 14. RESULTS: In multivariable analysis those born of
      mothers who consumed 3+ glasses during pregnancy were at increased risk to report
      drinking 3+ glasses compared with those whose mothers reported no drinking or
      drinking up to 2 glasses. Comparisons controlling for drinking before pregnancy
      and at age 5 found the averaged odds ratio of maternal drinking in pregnancy on
      risk of reporting alcohol consumption of 3 and more glasses at age 14 was 2.74
      (CI 1.70, 4.22). CONCLUSION: Our study suggests that they maybe a biological
      origin of early drinking. Further studies are needed to better disentangle the
      nature of the association and the role of other possible confounding factors.

PMID- 18639393
TI  - Development of a Readiness Ruler for use with alcohol brief interventions.
AB  - BACKGROUND: A quick method of assessing readiness to change was needed for a
      major study of implementing screening and alcohol brief intervention in England.
      For this purpose, a Readiness Ruler that had been validated among a sample of
      male college students in the USA was adapted and applied to a sample of excessive
      drinkers in a general medical practice located in a deprived area of Gateshead,
      England. METHODS: 72 participants identified as excessive drinkers by health
      professionals completed a single-item Readiness Ruler, the 12-item Readiness to
      Change Questionnaire (RCQ) and the AUDIT questionnaire. RESULTS: In terms of
      concurrent validity, the relationships between the Readiness Ruler, on the one
      hand, and either stage of change allocation or a dimensional score derived from
      the RCQ, on the other hand, were highly significant but weaker than expected.
      When patients who endorsed the "maintenance" point on the Readiness Ruler were
      excluded from the analysis, the above relationships were considerably
      strengthened for reasons that are discussed. On this basis and with another small
      change, a final Readiness Ruler was developed. CONCLUSION: If the validity of the
      Readiness Ruler is confirmed in subsequent research, a quick and simple way of
      measuring readiness to change will be available for research or clinical work
      with alcohol brief interventions.

PMID- 18639394
TI  - Effect of taxon sampling on recovering the phylogeny of squamate reptiles based
      on complete mitochondrial genome and nuclear gene sequence data.
AB  - The complete nucleotide sequences of the mitochondrial (mt) genomes of three
      species of squamate lizards: Blanus cinereus (Amphisbaenidae), Anguis fragilis
      (Anguidae), and Tarentola mauritanica (Geckkonidae) were determined anew. The
      deduced amino acid sequences of all 13 mt protein-coding genes were combined into
      a single data set and phylogenetic relationships among main squamate lineages
      were analyzed under maximum likelihood (ML) and Bayesian Inference (BI). Within
      Squamata, the monophyly of Iguanidae, Anguimorpha, Amphisbaenia, Gekkota,
      Serpentes, and Acrodonta received high statistical support with both methods. It
      is particularly striking that this is the first molecular analysis that recovers
      the monophyly of Scincomorpha (including Scincidae, Xantusiidae, Cordylidae, and
      Lacertidae), although it is only supported in the Bayesian analysis, and it is
      sensitive to changes in the outgroup (see below). Phylogenetic relationships
      among the main squamate lineages could not be resolved with ML but received
      strong support with BI (above 95%). The newly reconstructed phylogeny of
      squamates does not support the Iguania-Scleroglossa split. Acrodonta and
      Serpentes form a clade, which is the sister group of the remaining squamate
      lineages. Within these, Gekkota were the first branching out, followed by
      Amphisbaenia, and a clade including Anguimorpha as sister group of Scincomorpha +
      Iguanidae. The recovered topology differed substantially from previously reported
      hypotheses on squamate relationships, and the relative effect of using different
      outgroups, genes, and taxon samplings were explored. The sister group
      relationship of Serpentes + Acrodonta, and their relative basal position within
      Squamata could be due to a long-branch attraction artifact. Phylogenetic
      relationships among Scincomorpha, Amphisbaenia, and Anguimorpha were found to be
      rather unresolved. Future improving of squamate phylogenetic relationships would
      rely on finding snake and acrodont species with slower mt evolutionary rates,
      ensuring thorough taxon coverage of squamate diversity, and incorporating more
      nuclear genes with appropriate evolutionary rates.

PMID- 18639395
TI  - Development and validation of a SYBR green real-time PCR for the quantification
      of porcine circovirus type 2 in serum, buffy coat, feces, and multiple tissues.
AB  - The emergence of multiple genotypes of PCV2, as demonstrated by phylogenetic
      analysis of whole genome or capsid sequences, makes it necessary to have
      quantitative diagnostic assays that perform equally well on all strains. The
      objectives of this study were to develop and validate a novel real-time
      polymerase chain reaction (PCR) assay targeting the highly conserved rep gene
      (ORF1) and investigate the effects of diagnostic specimen choice on its
      performance. The assay was tested in naturally infected conventional pigs,
      experimentally infected gnotobiotic pigs, and plasmid-spiked negative serum, lung
      tissue, and feces and found to have a linear detection range of 2.2x10(3) to
      2.2x10(10) copies of PCV2 per mL. The assay successfully detected and quantified
      PCV2 DNA in serum, buffy coat, feces, and multiple lymphoid (bronchial,
      mesenteric, and superficial inguinal lymph nodes; thymus; tonsil; ileal Peyer's
      patches; and spleen), and non-lymphoid (myocardium; lung; kidney; liver; and
      gluteal muscle) tissues from naturally infected pigs. Across all tissues and sera
      of naturally infected pigs, the mean PCV2 concentration was 3.0logs higher in
      wasting versus non-wasting pigs. PCV2 concentration measured by tissue culture
      and immunohistochemical staining in homogenized liver samples of experimentally
      infected gnotobiotic pigs were compared to the concentrations estimated by
      quantitative PCR. Similar trends were noted with increasing PCV2 concentration
      detected in subclinically infected to severely PMWS-affected pigs across all
      assays. Our diagnostic assay was developed with a conserved target sequence, and
      performed efficiently in quantification of PCV2 in a variety of tissues from
      naturally and experimentally infected pigs.

PMID- 18639396
TI  - Motor impairment and low achievement in very preterm children at eight years of
      age.
AB  - AIM: To examine the concurrence of motor impairment and academic underachievement
      in a group of very preterm children at 8 years of age. METHODS: All surviving
      children with a gestational age less than 30 weeks, admitted to the neonatal
      intensive care unit between 1987 and 1997, were prospectively enrolled in
      developmental follow-up. Children with a neurosensory disability or a low
      intelligence score (FSIQ < or = 75 points) were excluded. At 8 years of age the
      Bruininks Oseretsky Test of Motor Proficiency and standardised tests of academic
      achievement were administered to a sample of 323 very preterm children. RESULTS:
      One hundred and one (31.3%) of these very preterm children were identified as
      having Developmental Coordination Disorder (DCD). Of the children with DCD, 54.4%
      also had underachievement in literacy and/or numeracy. As the severity of motor
      impairment increased so too did the severity and complexity of underachievement.
      Significantly fewer children with motor impairments participated in after-school
      sporting activities. Children with DCD required more mechanical ventilation
      support during their hospital admission. CONCLUSIONS: This study demonstrated
      that a significant proportion of children born very preterm find both motor and
      academic skills difficult in early school years.

PMID- 18639397
TI  - Short-term nutritional treatments grazing legumes or feeding concentrates
      increase prolificacy in Corriedale ewes.
AB  - We tested whether short periods of increased nutrition will improve ovulation
      rate and prolificacy, irrespective of the method used to synchronise the cycles
      of the ewes. In Experiment 1, we used 138 Corriedale ewes to evaluate two
      factors: synchronization treatment (sponges versus a single injection of
      prostaglandin) and type of pasture (native versus improved with Lotus
      corniculatus). Ewes were mated at the end of the grazing period and prolificacy
      was evaluated at lambing. Grazing Lotus corniculatus for 12 days tended to
      increase the number of twin lambs born (P=0.09). The percentage of ewes showing
      oestrus during a 9-day period was similar among synchronization treatments.
      Animals in Experiments 2 (n=282) and 3 (n=288) were allocated to a control group
      or a group fed a supplement of corn grain and soybean meal for 7 days. Ewes
      received 2 prostaglandin injections and the supplement was fed from Days 11 to 17
      after the second prostaglandin. Ovulation rate was measured in 65 (Experiment 2)
      and 61 (Experiment 3) ewes that were confirmed to have consumed the supplement
      and showed oestrus in a 4-day period. The supplement increased ovulation rate by
      14% in both experiments (P<0.05). We conclude that Corriedale ewes can respond
      with increases in prolificacy to a 12-day period grazing Lotus corniculatus and
      in ovulation rate to 7 days feeding with a supplement rich in energy and protein.
      Moreover, in these studies, prostaglandin was as effective as sponges for
      synchronising oestrus, an important factor in future decisions about hormonal
      management of fertility.

PMID- 18639398
TI  - Panax ginseng induces anterograde transport of pigment organelles in Xenopus
      melanophores.
AB  - Melanophores from Xenopus laevis are pigmented cells, capable of quick colour
      changes through cyclic adenosine 3':5'-monophosphate (cAMP) coordinated transport
      of their intracellular pigment granules, melanosomes. In this study we use the
      melanophore cell line to evaluate the effects of Panax ginseng extract G115 on
      organelle transport. Absorbance readings of melanophore-coated microplates,
      Correlate-EIA direct cAMP enzyme immunoassay kit, and western blot were used to
      measure the melanosome movement and changes in intracellular signalling. We show
      that Panax ginseng induces a fast concentration-dependent anterograde transport
      of the melanosomes. No significant increase in the cAMP level was seen and pre
      incubation of melanophores with the protein kinase C (PKC) inhibitor EGF-R
      Fragment 651-658 (M-EGF) only partly decreased the ginseng-induced dispersion. We
      also demonstrate that Panax ginseng, endothelin-3 (ET-3) and alpha-melanocyte
      stimulating hormone (MSH) stimulate an activation of mitogen activated protein
      kinase (MAPK). Pre-incubation with M-EGF decreased the MAPK activity induced by
      ET-3 and MSH, but again only marginally affected the response of Panax ginseng.
      Thus, in melanophores we suggest that Panax ginseng stimulates an anterograde
      transport of pigment organelles via a non-cAMP and mainly PKC-independent
      pathway.

PMID- 18639399
TI  - Fatal methanol intoxication with different survival times--morphological findings
      and postmortem methanol distribution.
AB  - Three corresponding cases of fatal methanol intoxication with different survival
      times were investigated ante-mortem and postmortem. Ante-mortem serum methanol
      concentrations were determined during treatment in hospital for 4 days.
      Furthermore, postmortem distribution of methanol in various tissues and fluids
      was measured after autopsy. Morphological and toxicological findings are
      discussed based on the literature. The morphological findings correlated with the
      different survival times. The results of the toxicological analyses were partly
      in keeping with previously published data. Interestingly, very high methanol
      levels were determined in brain with very low concentrations in femoral venous
      blood. These results may have implications for postmortem toxicological analysis,
      brain death diagnosis and organ explanation for transplantation.

PMID- 18639400
TI  - An autopsy case of an infant with Joubert syndrome who died unexpectedly and a
      review of the literature.
AB  - The present report describes the unexpected death of a 6-month-old female infant
      who had been clinically diagnosed with Joubert syndrome. This is a relatively
      rare congenital neurological disorder characterized by hypoplasia/aplasia of
      cerebellar vermis, which transmits information from the body to the cerebellum,
      and is associated with respiratory dysfunction, abnormal eye movements, and
      developmental delay. The infant was found dead in bed and the immediate cause of
      death was determined as aspiration of vomit which may have been induced by a
      neurological disorder related to hypoplasia of the cerebellar vermis. These
      findings, together with a review of previous clinical case reports, suggest that
      Joubert syndrome should be considered as a predisposition to sudden unexpected
      death in infants mainly due to aspiration or complicated infection.

PMID- 18639401
TI  - Exact solutions to Bayesian and maximum likelihood problems in facial
      identification when population and error distributions are known.
AB  - The reliability of traditional photogrammetric identification techniques using a
      small number of facial landmarks has recently come in for criticism. However, the
      transformation of parameters into a new face space in which the error
      distributions are orthogonal, yields a maximum likelihood solution to the problem
      of identifying a photographed face from a small, known, population which, in a
      simulated example, raises the success rate from 20% to 93%. A full transformation
      yielding simultaneously independent population and error distributions can be
      derived from raw population and error data using a straightforward computer
      procedure. Such a transformation facilitates computations for the situation where
      a single suspect is held in custody and the likelihood ratio of his being
      identical with a photograph is desired. It seems premature to condemn
      photogrammetry until the more efficient data-analysis approach outlined in this
      paper has been applied and tested.

PMID- 18639402
TI  - "I am flying to the stars"--suicide by aircraft in Germany.
AB  - In 2006, 67 persons were killed in aircraft accidents in Germany and involving
      German aircrafts abroad. In spite of extensive investigation of each aircraft
      accident, there are no reliable data as to the number of suicides by aircraft. We
      report on a 50-year-old man who committed suicide by willfully crashing his Beech
      "Sierra" aircraft minutes after take off from an airport close to the town of
      Rendsburg, Germany. Before killing himself, the intoxicated pilot had sent an SMS
      announcing his suicide plans to a friend. The findings of the medico-legal
      investigation and the results of a review of aircraft accident reports by the
      German Federal Bureau of Aircraft Accidents Investigation (BFU) regarding
      suicidal plane crashes are presented.

PMID- 18639403
TI  - Forensic discrimination of blue ballpoint pen inks based on thin layer
      chromatography and image analysis.
AB  - This article aims to provide a new and fast method for differentiation of inks on
      a questioned document. The data acquisition was carried out by designing specific
      image analysis software for evaluating thin layer chromatograms (TLC-IA). The ink
      spot was extracted from the document using methanol and separated by TLC using
      plastic sheet silica gel 60 without fluorescent indicator, and a mixture of ethyl
      acetate, ethanol, and water (70:35:30, v/v/v) as mobile phase. To discriminate
      between different pen inks, new software was designed on the basis of intensity
      profile of red, green, and blue (RGB) characteristic. In practice, after
      development of chromatogram, the chromatograms were scanned by ordinary office
      scanner, intensity profiles of RGB characteristics on the development straight of
      each sample were produced and compared with the mentioned software. RGB profiles
      of ballpoint inks from various manufacturers showed that the patterns in most
      cases were distinctly different from each other. This new method allowed
      discriminating among different pen inks with a high reliability and the
      discriminating power of 92.8%. Blue ballpoint pen inks of 41 different samples
      available on the local market were successfully analyzed and discriminated.

PMID- 18639404
TI  - Comparison between effective radiation dose of CBCT and MSCT scanners for
      dentomaxillofacial applications.
AB  - OBJECTIVES: To compare the effective dose levels of cone beam computed tomography
      (CBCT) for maxillofacial applications with those of multi-slice computed
      tomography (MSCT). STUDY DESIGN: The effective doses of 3 CBCT scanners were
      estimated (Accuitomo 3D, i-CAT, and NewTom 3G) and compared to the dose levels
      for corresponding image acquisition protocols for 3 MSCT scanners (Somatom
      VolumeZoom 4, Somatom Sensation 16 and Mx8000 IDT). The effective dose was
      calculated using thermoluminescent dosimeters (TLDs), placed in a Rando Alderson
      phantom, and expressed according to the ICRP 103 (2007) guidelines (including a
      separate tissue weighting factor for the salivary glands, as opposed to former
      ICRP guidelines). RESULTS: Effective dose values ranged from 13 to 82 microSv for
      CBCT and from 474 to 1160 microSv for MSCT. CBCT dose levels were the lowest for
      the Accuitomo 3D, and highest for the i-CAT. CONCLUSIONS: Dose levels for CBCT
      imaging remained far below those of clinical MSCT protocols, even when a
      mandibular protocol was applied for the latter, resulting in a smaller field of
      view compared to various CBCT protocols. Considering this wide dose span, it is
      of outmost importance to justify the selection of each of the aforementioned
      techniques, and to optimise the radiation dose while achieving a sufficient image
      quality. When comparing these results to previous dosimetric studies, a
      conversion needs to be made using the latest ICRP recommendations.

PMID- 18639405
TI  - SPE-HPTLC of procyanidins from the barks of different species and clones of
      Salix.
AB  - A SPE-HPTLC method was developed for the qualitative and quantitative analysis of
      procyanidin B(1) in willow barks. The chromatography was performed on HPTLC
      silica gel layer with the mobile phase chloroform-ethanol-formic acid (50:40:6
      v/v/v), in the Automatic Developing Chamber-ADC 2. The methanol extracts from
      willow barks were purified by SPE method on RP-18 silica gel columns with
      methanol-water (7:93 v/v) as the eluent. The presence of procyanidin B(1) was
      revealed in the majority of investigated willow barks. The content of procyanidin
      B(1) varied from 0.26 mg/g in the extract of Salix purpurea clone 1067-2.24 mg/g
      in the extract of Salix alba clone 1100. The method was validated for linearity,
      precision, LOD, LOQ and repeatability.

PMID- 18639406
TI  - Development and validation of an HPLC method for vancomycin and its application
      to a pharmacokinetic study.
AB  - A rapid and simple method of high performance liquid chromatography with UV
      detection for the quantification of vancomycin in artificial perfusion fluid and
      lung tissue samples has been developed and validated. Chromatographic separation
      was carried out in a Nucleosil 120 C(18) 5 microm column (length, 15 cm; inner
      diameter, 0.4 cm) using a mixture of 0.05 M NH(4)H(2)PO(4) (pH 4)-acetonitrile
      (92:8, v/v) as the mobile phase at a flow rate of 1 mL/min, with UV detection at
      220 nm. The method used for the vancomycin quantification showed linearity for
      concentration ranges of 0.1-2, 2-15 and 15-250 microg/mL, with r(2)=0.9985,
      0.9996 and 0.9985, respectively. The limit of quantification of the method was
      0.1 microg/mL and the coefficients of variation of the between- and within-day
      precision showed values between 0.6% and 7.0%. The retention time of vancomycin
      was 8.5 min. The method was used successfully to study the pharmacokinetics of
      vancomycin in isolated rat lung after its administration through the systemic and
      inhalatory routes.

PMID- 18639408
TI  - Acute infectious peritonitis caused by Vibrio fluvialis.
AB  - Vibrio fluvialis is a Gram-negative, oxidase-producing, halophilic bacterium
      that, as a pathogen, has been implicated mainly as a cause of gastroenteritis. We
      describe a case of V. fluvialis peritonitis after a traffic accident that is, to
      our knowledge, the 1st report of non-continuous ambulatory peritoneal dialysis
      related acute peritonitis caused by this organism.

PMID- 18639409
TI  - Computer-mediated infertility support groups: an exploratory study of online
      experiences.
AB  - OBJECTIVE: Over recent years the Internet has become an increasingly popular
      source of support and information for infertility, with a growing number of
      online support groups now available to individuals affected by fertility
      problems. The aims of the present study were therefore to explore the online
      experiences of individuals accessing infertility support groups via the Internet.
      METHODS: Ninety-five participants who were recruited from several online
      infertility support groups completed an online questionnaire containing a series
      of open-ended questions. Responses to the open-ended questions were analysed
      using inductive thematic analysis. RESULTS: The thematic analysis revealed five
      recurrent themes, which were labelled: 'unique features of online social
      support', 'improved relationship with partner', 'reduced sense of isolation',
      'information and empowerment', and 'negative aspects of online communities.'
      CONCLUSIONS: This study suggests that the majority of participants considered
      there to be a range of important benefits from accessing online communities.
      However the results also demonstrate that there are a number of disadvantages to
      online infertility support groups that may have an impact on the experiences of
      infertile individuals. PRACTICE IMPLICATIONS: Online support groups may provide a
      valuable forum through which health care professionals can better understand and
      support the psychosocial needs of individuals experiencing infertility.

PMID- 18639407
TI  - Reconsideration of viral protein immunoblotting for differentiation of human
      herpes simplex viruses.
AB  - Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are ubiquitous human
      pathogens that infect their hosts for life and reactivate to cause disease at or
      near the initial site of infection. As the incidence of genital HSV-1 infections
      increase, there is an increased demand for valid viral typing diagnostics. In
      this report, we reconsidered and developed a triple-phase immune-typing procedure
      that compares differences in electrophoretic mobilities of viral ICP4, ICP27, and
      VP22 proteins between HSV-1 and HSV-2 strains. We isolated and immunotyped 5
      primary HSV-1 strains derived from orofacial, ocular, and genital areas along
      with 2 primary HSV-2 strains from the genital area. Advantages of this
      methodology include its general technical simplicity, sensitivity, and ability to
      definitively type HSV. It is anticipated that this methodology will be useful in
      distinguishing viruses obtained in clinical cultures.

PMID- 18639410
TI  - A pilot-study to identify the feasibility of an Internet-based coaching programme
      for changing the vascular risk profile of high-risk patients.
AB  - OBJECTIVE: To evaluate the feasibility of a web-based coaching programme for
      vascular risk factor treatment, to describe the patterns of use and to measure
      changes in risk factors. METHODS: Patients with a clinical manifestation of
      arterial disease and Internet access were asked to participate in the nurse-led
      Internet-based risk factor management programme. At the first clinic visit, a
      personalized action plan was made for the treatment of risk factors. Patients
      were instructed on communication with a specialized nurse through Internet and
      encouraged to enter self-measured risk factor levels at their personalized
      website. The nurse practitioner replied on working days and gave feedback,
      support, and recommendations on lifestyle and medical treatment. After 6 months,
      risk factors were re-measured. RESULTS: Fifty patients participated, 70% were
      overweight, 64% had hypertension, 42% hyperlipidemia, and 24% smoked at baseline.
      During 6 months, the log-in average at the individual website was 35 times per
      patient (1.3 log-ins/week); while the nurse practitioner logged-in at the overall
      website 23 times/week. The website was hardly used by five patients. Most e-mail
      messages were sent by patients for hypertension (211 times) and obesity (203
      times), whereas the nurse practitioner sent nearly twice as many e-mail messages
      for hypertension (400 times) and obesity (455 times). The level of most risk
      factors decreased and the fraction of achieved treatment goals increased (blood
      pressure from 36 to 58%, LDL-cholesterol from 58 to 64%, glucose from 64 to 82%).
      CONCLUSIONS: A web-based vascular risk factor intervention programme is feasible;
      it is frequently used by patients and suitable to decrease the level of several
      risk factors. It has the promise of being an efficacious intervention for risk
      factor sanitation in patients with symptomatic vascular disease. PRACTICE
      IMPLICATIONS: An Internet-based individualised risk management programme could
      make patients aware of their self-management capability and may contribute to
      risk factor reduction.

PMID- 18639411
TI  - Applying patient perspectives on caring to curriculum development.
AB  - OBJECTIVE: To report how patient viewpoints on caring inform curriculum
      development for teaching sessions on delivering bad news, making the transition
      to palliative care, and communicating about a medical error. METHODS: We
      conducted focus groups that used patients recruited from the surrounding
      community to view videotapes of physicians delivering bad news, talking with a
      patient about palliative care, and communicating about a medical error. We used
      focus group results, combined with evidence from the medical literature to inform
      curriculum content for workshops conducted with Internal Medicine and Family
      Medicine residents at the University of Massachusetts Medical School. RESULTS:
      Patient perspectives on caring gathered through focus groups differed in
      significant ways from the existing medical literature on caring when providers
      are communicating in the challenging situations that were depicted. Our data
      pointed out that individual reactions were unique and sometimes contradictory in
      that one person saw behavior as caring that others thought was uncaring.
      Participants often used qualifiers in their comments like "appropriate" amounts
      of information, "measured" empathy, chooses words carefully to reflect the
      relative nature of caring. "Arranges to meet healthcare needs," an issue that
      extends beyond the encounter, was seen as a new component of caring not
      previously described. Applying these concepts to curriculum required that we not
      only focus on the behavioral skills involved in these tasks, but also the
      processes of assessing patient's informational and emotional needs, and then
      taking steps to meet them, while adjusting behavior in real time to meet patients
      needs for caring. Workshops delivered were highly evaluated by residents.
      CONCLUSION: Patient perspectives on caring when providers deliver bad news,
      discuss transitions to palliative care, and communicate about a medical error
      reinforce that patient expectations for caring are highly contextualized and
      physician behavior needs to be individualized. We taught residents not only
      behavioral skills, but also the process skills of anticipating patient reactions,
      recognizing patient clues, planning and choosing effective strategies on the fly,
      and assessing one's own performance characteristic of communication expertise.
      PRACTICE IMPLICATIONS: Teaching caring attitudes with challenging communication
      tasks requires that learners appreciate and value not only caring behaviors but
      also learn the process by which they must adjust and titrate their actions to
      meet patient needs.

PMID- 18639412
TI  - Cerebral oximetry does not correlate with electroencephalography and
      somatosensory evoked potentials in determining the need for shunting during
      carotid endarterectomy.
AB  - OBJECTIVE: Several reports in the literature have described the value of regional
      cerebral oximetry (rSO(2)) as a neuromonitoring device during carotid
      endarterectomy (CEA). The use of rSO(2) is enticing because it is simpler and
      less expensive than other neuromonitoring modalities. This study was performed to
      compare the efficacy of rSO(2) with electroencephalography (EEG) and median nerve
      somatosensory evoked potentials (SSEP) in determining when to place a shunt
      during CEA. METHODS: From October 2000 to June 2006, 323 CEAs were performed
      under general anesthesia by six surgeons. Shunting was done selectively on the
      basis of EEG and SSEP monitoring under the auspices of an intraoperative
      neurophysiologist. All patients were retrospectively reviewed to see if
      significant discrepancies existed between EEG/SSEP and rSO(2). RESULTS: Twenty
      four patients (7.4%) showed significant discrepancies. Sixteen patients showed no
      significant EEG/SSEP changes, but profound changes occurred in rSO(2), and no
      shunt was placed. In seven patients there was no change in rSO(2) but a profound
      change occurred in EEG/SSEP, and shunts were placed. In one patient early in the
      series, the EEG and SSEP were unchanged but the rSO(2) dropped precipitously, and
      a shunt was placed. In the 299 patients who showed no discrepancies, 285 were not
      shunted and 14 required a shunt. Two strokes occurred in the entire series
      (0.6%), none intraoperatively. Shunts were placed in 23 patients (7%). The
      sensitivity of rSO(2) compared with EEG/SSEP was 68%, and the specificity was
      94%. This gave a positive-predictive value of 47% and a negative-predictive value
      of 98%. CONCLUSIONS: Relying on rSO(2) alone for selective shunting is
      potentially dangerous and might have led to intraoperative ischemic strokes in
      seven patients and the unnecessary use of shunts in at least 16 patients in this
      series. The use of rSO(2) adds nothing to the information already provided by EEG
      and SSEP in determining when to place a shunt during CEA.

PMID- 18639413
TI  - Midterm outcome after the distal revascularization and interval ligation (DRIL)
      procedure.
AB  - BACKGROUND: The distal revascularization and interval ligation (DRIL) procedure
      has evolved as the optimal treatment for access-related hand ischemia despite
      concerns about its durability. This study was designed to review our
      institutional experience and objectively define its mid-term outcome. METHODS: A
      retrospective review of all patients undergoing the DRIL procedure was performed.
      The diagnosis of severe hand ischemia was made based primarily upon clinical
      presentation, but confirmed with noninvasive imaging in select cases. The DRIL
      conduit was selected based upon noninvasive imaging (vein conduit criteria:
      saphenous > arm; diameter >/=3 mm) and the proximal anastomosis was positioned
      >/=7 cm from the access anastomosis. The DRIL bypasses were followed in a graft
      surveillance protocol and remedial procedures performed as dictated by clinical
      or ultrasound scan findings. RESULTS: Sixty-four DRIL procedures were performed
      in 61 patients (age - 58 +/- 13 standard deviation [SD], female - 62%, diabetic -
      72%). The index access procedures included: autogenous brachiocephalic - 46%,
      autogenous brachiobasilic - 31%, autogenous brachioaxillary translocated femoral
      vein - 20%, other -3%. The precipitating symptoms were pain (25%), paresthesia
      (34%), motor dysfunction (24%), and tissue loss (17%); a pre-emptive DRIL was
      performed in 5 patients. The timing of the DRIL relative to the index access was
      dictated by the symptoms: <24 hrs - 19%; 1 day </= DRIL </=7 days - 29%; 7 days
      </= DRIL </=30 days - 8%; >30 days - 44%. Perioperative mortality rate was 3% and
      the complication rate was 22% (wound - 14%). The DRIL procedure relieved the
      ischemic symptoms in 78% of the cases (residual symptoms: paresthesia - 13%; pain
      - 5%; tissue loss - 4%; motor - 2%). The DRIL also resulted in significant (P <
      .05) increases in both the wrist/brachial index (WBI) and digital/brachial index
      (DBI) with the mean increases of 0.34 +/- 0.26 and 0.41 +/- 0.21, respectively.
      The primary DRIL patency rates (+/- standard error of the mean [SEM]) were 77 +/-
      8%, 74 +/- 9%, and 71 +/- 9% at 1 year, 3 years, and 5 years, respectively, while
      the corresponding secondary patency rates were 81 +/- 7%, 76 +/- 9%, and 76 +/-
      9%, and the survival rates were 71 +/- 6%, 59 +/- 7%, and 33 +/- 9%. The index
      access procedure went on to mature sufficiently for cannulation in 68% of the
      cases when the DRIL was performed early (ie, <3 months from index access); all
      accesses functional at the time of the DRIL were used for dialysis throughout the
      perioperative period. CONCLUSION: The DRIL procedure safely and effectively
      relieves the symptoms of severe access-related hand ischemia while preserving the
      access. The midterm results suggest that the DRIL bypasses are durable, although
      long-term graft surveillance may be justified given the observed failures.

PMID- 18639414
TI  - Giant cell arteritis: heterogeneity in clinical presentation and imaging results.
AB  - OBJECTIVE: Giant cell arteritis (GCA) is commonly known for its clinical
      presentation of temporal arteritis. However, GCA affects large arteries,
      predominantly the aorta and its proximal branches, in up to 75% of cases. We
      describe the clinical presentation and diagnostic test results of patients with
      large-vessel GCA. METHODS: Case description of 11 patients with large-vessel GCA
      diagnosed consecutively in our hospital. RESULTS: The clinical presentation of
      large-vessel GCA is highly variable, from systemic inflammation to aortic
      rupture. Imaging shows variable abnormalities, but 18-fluorodeoxyglucose positron
      emission-tomography (18-FDG PET) seems to be a sensitive and reasonably specific
      diagnostic test for large-vessel GCA. CONCLUSION: Large-vessel GCA is a
      clinically heterogeneous condition. 18-FDG PET should be considered in the
      diagnostic work-up of suspected cases. Since this disorder has a high
      complication rate, and is responsive to treatment with corticosteroids, a high
      level of clinical suspicion is warranted.

PMID- 18639416
TI  - Basic fibroblast growth factor slow release stent graft for endovascular aortic
      aneurysm repair: a canine model experiment.
AB  - OBJECTIVE: Persistent endoleak and endotension, complications after endovascular
      aortic repair, may be caused by an unorganized thrombus inside the aneurysm. The
      experimental study was designed to evaluate the effectiveness of stent grafts
      (S/Gs) with slow release of basic fibroblast growth factor (bFGF) for the
      organization. METHODS: The S/Gs were constructed of self-expanding Z stent
      covered with expanded polytetra fluoroethylene graft, and coated with elastin to
      be able to bind and slowly release bFGF. Five elastin-coated S/Gs with bFGF (bFGF
      S/Gs) and without bFGF (C-S/Gs) were placed in the normal canine aorta
      respectively. The thoracic aortic aneurysm models were surgically created with a
      jugular vein patch in 12 beagles. S/Gs with six holes, for creating endoleaks,
      were used in the experiment of aneurysmal repair. The bFGF-S/Gs (n = 6) and C
      S/Gs (n = 6) were implanted. The beagles were sacrificed at two weeks after the
      endovascular procedure and examined histologically. RESULTS: The bFGF-S/Gs
      induced six times the intimal proliferation of the C-S/Gs in normal aorta. Twelve
      animals had successfully created aneurysms, and had endoleaks just after the
      endovascular procedure. At two weeks after the endovascular procedure, the
      percentage of fibrous area in the aneurysmal cavity treated with bFGF-S/G (35.7
      +/- 4.3%) was significantly greater than C-S/G (13.6 +/- 2.2%) (P < .01).
      CONCLUSION: bFGF-S/Gs are effective for accelerating organization of the aneurysm
      cavity and developing neointima. Further research on bFGF-S/Gs would clarify the
      association of endoleaks.

PMID- 18639417
TI  - Effect of the anticoagulant therapy in the incidence of post-thrombotic syndrome
      and recurrent thromboembolism: Comparative study of enoxaparin versus coumarin.
AB  - OBJECTIVE: We evaluated the effect of long-term anticoagulant treatment
      (enoxaparin vs coumarin) in patients with deep venous thrombosis (DVT) as to
      incidence of post-thrombotic syndrome (PTS) and recurrent venous thromboembolism.
      We also analyzed the impact of thrombus regression after the anticoagulant
      treatment for these two outcomes. METHODS: A prospective study was designed in
      which 165 patients with symptomatic, unilateral, first-episode DVT were
      randomized to a long-term anticoagulant treatment with coumarin or enoxaparin
      during at least 3 months. The rate of thrombus regression was defined as the
      difference in Marder score after 3 months of treatment by venography. Follow-up
      was performed at 3, 6, and 12 months, and yearly thereafter for 5 years. Venous
      disease was related to pathologic severity of PTS according to the validated
      scale of Villalta as rated by a physician blinded to treatment. Recurrence of
      symptomatic venous thromboembolism was documented objectively. RESULTS: The 5
      year follow-up period was completed for 100 patients (enoxaparin, 56; coumarin,
      44). A lesser incidence of PTS was observed in the enoxaparin group (39.3%
      absent, 19.6% severe) than in the coumarin group (29.5% absent, 29.5% severe),
      although this difference was not statistically significant. The accumulated
      recurrence rate was 19.3% with enoxaparin compared with 36.6% with coumarin (P =
      .02). Although the mean Marder score was significantly improved in both groups
      (49.1% for enoxaparin vs 24.0% for coumarin; P = .016), a lower reduction in
      thrombus size was associated with higher clinical events of recurrence (hazard
      ratio = 1.97; 95% CI, 1.06-3.66; P = .032). A significant inverse correlation was
      also found between the degree of thrombus regression at 3 months and the
      incidence at 5 years of PTS (P = .007). CONCLUSIONS: Residual venous thrombosis
      is an important risk factor for recurrent thromboembolism and PTS. A greater
      reduction in thrombus size was associated with lesser clinical events of
      recurrence and consequently a lesser rate of PTS. However, despite a greater
      recanalization with enoxaparin, the incidence of PTS was similar between both
      treatment groups, probably because of the small sample size. Further
      investigations are needed to clarify the implication of the anticoagulant
      treatment in the severity of PTS.

PMID- 18639418
TI  - Endovenous laser and echo-guided foam ablation in great saphenous vein reflux:
      one-year follow-up results.
AB  - BACKGROUND: Great saphenous vein (GSV) reflux is the most frequent form of venous
      insufficiency in symptomatic patients and is commonly responsible for varicose
      veins of the lower extremity. This non-randomized prospective controlled study
      was designed to test the hypothesis that 1) endovenous laser treatment is more
      effective than foam sclerotherapy in the closure of the refluxing GSV (as
      measured by degree of great saphenous vein reflux and venous clinical severity
      score changes) and 2) to record the associated complications of echo-guided
      endovenous chemical ablation with foam and endovenous laser therapy for the
      treatment of great saphenous vein reflux and to further identify risk factors
      associated with treatment failure. METHODS: Between January 1, 2006 and June 25,
      2006, patients seeking treatment of varicose veins at a private practice of
      vascular medicine were assessed for the study. Inclusion criteria were: 1)
      presence of great saphenous vein reflux and 2) C2-6, Epr, A s, according to the
      CEAP classification. The selected patients consented into the study and were
      allowed to choose between foam (53 patients) or laser (45 patients) treatment.
      Duplex examinations were performed prior to treatment and at seven and 14 days,
      four weeks, six months, and one year after treatment. Venous clinical severity
      score was assessed pre-treatment and at one year post-procedure. RESULTS: The
      cohorts showed no statistically significant differences in age, sex, clinical and
      anatomical presentation, great saphenous vein diameter, and venous clinical
      severity score before the treatments. After one year follow up, occlusion of the
      great saphenous vein was confirmed in 93.4% (42/45) of limbs studied in the laser
      group and 77.4% (41/53) of limbs in the foam group (P < .0465). Venous clinical
      severity score significantly improved in both groups (P < .0001). Procedure
      associated pain was higher in the laser group (P < .0082). Induration, phlebitis,
      and ecchymosis were the most common complications. Logistical regression and
      subgroups analysis shown that a larger great saphenous vein diameter measured
      before treatment was associated with treatment failure in the foam (odds ratio
      1.68, 95% CI 1.24-2.27, P < .0008) and in the laser group (odds ratio 1.91, 95%
      CI 1.02-3.59, P < .0428). A 90% treatment success is predicted for veins <6.5 mm
      in the foam group versus veins <12 mm in the laser group. CONCLUSIONS: Overall,
      endovenous laser ablation achieved higher occlusion rates than echo-guided
      chemical ablation with foam after one year follow-up. Matching the patient to the
      technique based on great saphenous vein diameter measured before treatment may
      assist in boosting the treatment success rate to >90%. A larger patient cohort
      followed and compared over a longer period of time would be required to confirm
      these findings.

PMID- 18639419
TI  - More patients are treated for nonruptured abdominal aortic aneurysms, but the
      proportion of women remains unchanged.
AB  - BACKGROUND: Large variations in the intervention rates for ruptured and
      nonruptured abdominal aortic aneurysm (AAA) over time have been reported, both
      decreasing and increasing numbers. Women have been reported to constitute an
      increasing proportion of patients treated for several manifestations of
      cardiovascular disease; whether a similar trend is true for AAA is not well
      understood. This study investigated recent temporal trends in a complete national
      register regarding the number and type of procedure performed for AAA, and
      outcome, with special emphasis on gender differences. METHODS: Data for all
      individuals treated for nonruptured or ruptured AAA in Sweden (1990 to 2005) were
      obtained from the Swedish National Board of Health and Welfare (NBHW). A total of
      14369 individuals were identified; 2327 (16%) were women. Date and type of
      intervention, date and cause of death, age, and sex were included in the
      statistical model. RESULTS: There was a relative annual increase in interventions
      for nonruptured AAA; 4% for women (P < .0001) and 2% for men (P < .0001). No
      significant trends were observed for interventions for rupture during the
      observation period. No significant increase in the proportion of women was
      recorded for nonrupture (17%) or rupture (15%). Women had higher crude 30-day
      mortality rate than men after treatment for both nonruptured (5.7% vs 4.9%) and
      ruptured (41.9% vs 36.8%) AAA. In a logistic regression model, survival improved
      over time after intervention for nonrupture (P < .0001) and rupture (P < .0001).
      Increasing age (P < .0001 for both nonrupture and rupture) but not sex (P = .49
      for non rupture and P = .42 for rupture) had a negative influence on mortality.
      CONCLUSION: Interventions for nonruptured but not for ruptured AAA increased over
      time, with an expected rapid increase of endovascular repair in the nonruptured
      group. The unchanged fraction of women over time possibly reflects the true
      distribution of AAA between the sexes. The outcome after treatment for both
      nonruptured and ruptured AAA improved, as anticipated, over time. No increase in
      mortality among women was recorded after adjustment for age.

PMID- 18639420
TI  - Usefulness of the Hardman index in predicting outcome after endovascular repair
      of ruptured abdominal aortic aneurysms.
AB  - OBJECTIVES: The Hardman index, which has five variables, has been recommended as
      a predictor of outcome after open repair of ruptured abdominal aortic aneurysms
      (RAAAs). It has been reported that the presence of three or more variables is
      uniformly fatal. The aim of this study was to test the same model in an
      independent series of RAAA patients undergoing endovascular repair. METHODS: A
      consecutive series of 41 patients undergoing endovascular repair for RAAA during
      an 8-year period was analyzed retrospectively. Thirty-day mortality and patient
      variables, including the five Hardman risk factors of age >76 years, serum
      creatinine >190 micromol/L, hemoglobin <9 g/dL, loss of consciousness, and
      electrocardiographic (ECG) evidence of ischemia, were recorded. The Hardman index
      and a revised version of the index with four variables (without ECG ischemia)
      were calculated and related to clinical outcome. RESULTS: Operative mortality was
      41% (17 of 41). On univariate analysis, only age >76 years (P = .01) and the use
      of local anesthesia (P < .0001) were statistically significant. Loss of
      consciousness (P = .05) showed a trend toward a higher mortality, albeit not
      statistically significant. On multivariate analysis, the use of local anesthesia
      was the only significant predictor of survival (odds ratio [OR], 0.03; 95%
      confidence interval [CI], 0.003-0.25, P = .001). Again, loss of consciousness
      showed an association with a higher chance of dying but did not achieve
      statistical significance (OR, 6.30; 95% CI, 0.93-42.51, P = .059). The original
      and revised versions of the Hardman index were both significantly associated with
      death (P = .02 and P = .001, chi(2) test for trend). The cumulative effect of 0,
      1, 2, and >/=3 risk factors on mortality was 0%, 27%, 36%, and 71% for the
      original index, and 12.5%, 21%, 60%, and 78% for the revised version,
      respectively. Four and two patients with a score of >/=3 in each version of the
      index survived endovascular repair. CONCLUSIONS: The Hardman index, with or
      without incorporating ECG ischemia, seems to be a simple and useful predictive
      tool in patients undergoing endovascular repair of RAAA, with the mortality rate
      increasing along with the Hardman score. However, the index cannot be used to
      accurately identify patients with no chance of survival after endovascular
      repair.

PMID- 18639421
TI  - Cost-effectiveness analysis of elective endovascular repair compared with open
      surgical repair of abdominal aortic aneurysms for patients at a high surgical
      risk: A 1-year patient-level analysis conducted in Ontario, Canada.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is a prevalent health condition
      affecting up to 14% of men and 6% of women. The objective of this study was to
      estimate the cost-effectiveness and cost-utility of elective endovascular
      aneurysm repair (EVAR) compared with open surgical repair (OSR) in patients at a
      high risk of surgical complications. METHODS: Patient-level cost and outcome data
      from a 1-year prospective observational study conducted at London Health Sciences
      Centre, London, Ontario, Canada, was used to determine the incremental cost per
      life-year gained and the incremental cost per quality-adjusted life year (QALY)
      gained of EVAR compared with OSR in patients with an AAA >5.5 cm and a high risk
      of surgical complications. The analysis was taken from a societal perspective and
      the time horizon was 1 year. To measure sampling uncertainty on costs and
      effects, nonparametric bootstrap techniques were applied. Uncertainty results
      were expressed using cost-effectiveness acceptability curves. Extrapolations of
      the 1-year results to a 5-year time horizon were conducted in sensitivity
      analyses. RESULTS: Between August 11, 2003, and April 3, 2005, 192 patients at a
      high risk of surgical complications were enrolled: 140 received EVAR and 52 OSR.
      Point estimates during a 1-year period showed that EVAR dominated OSR for high
      risk patients in terms of incremental cost per life-year gained and incremental
      cost per QALYs. However, bootstrap estimates for the two cost-effectiveness
      measures indicated there was a great deal of uncertainty regarding the costs and
      the QALYs and less uncertainty regarding life-years gained. If society was
      willing to pay $50,000 per life-year gained or per QALY gained, the probability
      of EVAR being cost-effective was found to be 0.76 and 0.55, respectively. Five
      year extrapolations indicated that EVAR was cost-effective compared with OSR.
      CONCLUSIONS: According to this 1-year observational study, EVAR may be a cost
      effective strategy compared with OSR for high-risk patients. Longer-term data are
      needed to decrease the uncertainty associated with the results.

PMID- 18639422
TI  - Outcomes of surgical management for popliteal artery aneurysms: an analysis of
      583 cases.
AB  - BACKGROUND: This study aimed to analyze outcomes of surgical management for
      popliteal artery aneurysms (PAA). METHODS: This is a retrospective analysis of
      prospectively collected data regarding operations for PAA obtained from 123
      United States Veterans Affairs Medical Centers as part of the National Surgical
      Quality Improvement Program. Univariate analyses and multivariate logistic
      regression were used to characterize 33 risk factors and their associations with
      30-day morbidity and mortality. Survival and amputation rates, observed at one
      and two years after surgery, were subject to life-table and Cox regression
      analyses. RESULTS: There were 583 operations for PAA in 537 patients during 1994
      2005. Almost all were in men (99.8%) and median age was 69 years (range, 34 to 92
      years). Most had multiple co-morbidities, 88% were ASA (American Society of
      Anesthesiologists) class 3 or 4, and 81% were current or past smokers (median
      pack-years = 50). Only 16% were diabetic. Serious complications occurred in 69
      (11.8%) cases, of which 37 (6.3%) required arterial-specific reinterventions.
      Eight patients died within 30 days, a mortality of 1.4%. Risk factors associated
      with increased complications included: African-American race (odds ratio [OR] 2.8
      [95% confidence interval 1.5-5.2], P = .002), emergency surgery (OR 3.8 [2.0
      7.0], P < .0001), ASA 4 (OR 1.9 [1.1-3.5], P = .04), dependent functional status
      (OR 2.5 [1.4-4.7], P = .004), steroid use (OR 3.2 [1.2-8.7], P = .03), and need
      for intraoperative red blood cell transfusion of any quantity (OR 6.3 [3.5-11.2],
      P < .0001). Independent predictors for complications in the multivariate model
      were dependent functional status (adjusted OR 2.1 [1.1-4.3], P = .049) and
      intraoperative transfusion (adjusted OR 4.5 [2.3-8.9], P = .0002). Postoperative
      bleeding complications within 72 hours independently predicted early amputation
      (adjusted OR 25.5 [1.7-393], P = .02). Unadjusted patient survival was 92.6% at
      one year and 86.1% at two years. Limb salvage in surviving patients was 99.0% at
      30 days, 97.6% at one year, and 96.2% at two years. Dependent preoperative
      functional status was the only factor predictive of worse two-year limb salvage
      (adjusted OR 4.6 [1.9-10.9], P = .001), but remained high at 88.2% versus 97.1%
      in independent patients. CONCLUSIONS: Surgical intervention for PAA is associated
      with low operative mortality and offers excellent two-year limb salvage, even in
      high-risk patients. Patients' preoperative functional status and perioperative
      blood transfusion requirements were the most predictive indicators of negative
      outcomes.

PMID- 18639423
TI  - Supra-aortic hybrid endovascular procedures for complex thoracic aortic disease:
      single center early to midterm results.
AB  - BACKGROUND: Hybrid technique with open surgical supra-aortic extra-anatomical
      bypasses (to provide a suitable proximal landing zone) and simultaneous or staged
      thoracic endovascular stent grafting is less invasive than open surgery in the
      treatment of complex aortic arch pathology. The aim of this study is to report
      our hybrid experience. METHODS: Retrospective review of prospectively collected
      computerized database. All patients had regular clinical and radiological
      computed tomography follow-up. RESULTS: Sixteen patients (13 males and 3 females)
      with mean age of 64.8 (range 51-79) were treated with hybrid techniques between
      May 2005 and September 2007. There were nine elective, two urgent (within 2 weeks
      of presentation), and five emergency cases. Thirteen patients had arch or
      proximal descending thoracic aortic aneurysms, and six patients had aortic
      dissections. All extra-anatomical bypasses were performed simultaneously with
      stent grafts, with mean operating time of 331.2 (range 195-540) minutes. Eight
      patients had right to left carotid-carotid cross-over graft, five had bifurcating
      grafts from ascending aorta to innominate and left carotid artery, two had left
      carotid to left subclavian artery, and one had left carotid to aberrant right
      subclavian bypass graft. All patients had Cook Zenith thoracic stent grafts.
      Deployment success was 100%, with no endoleak on completion angiogram. There was
      no mortality. Three patients had postoperative nondebilitating stroke and no
      paraplegia. The mean follow-up was 14 (range 1-27) months. One reintervention was
      required, and two patients had type II endoleak treated conservatively.
      CONCLUSION: Supra-aortic hybrid procedures in treating aortic arch pathology are
      safe and effective, and early- to midterm results are encouraging.

PMID- 18639424
TI  - Lower extremity arterial inflow is adversely affected in patients with venous
      disease.
AB  - BACKGROUND: Lower extremity chronic venous disease is due to venous hypertension
      resulting from reflux and/or obstruction. Studies of venous valvular function
      have validated and quantified valve closure times defining normal and abnormal
      valve function, and investigators have categorized the amount of venous reflux
      with validated criteria. However, hemodynamics of venous outflow obstruction
      remains poorly defined. The purpose of this study is to assess whether chronic
      venous disease alters arterial inflow at rest or during hyperemic limb challenge,
      and whether there are differences in patients with primary chronic venous
      insufficiency (1 degrees CVI) versus those with postthrombotic venous disease.
      METHODS: Twenty-two normal limbs and 32 limbs in patients with chronic venous
      disease (C-3 or greater) were examined between September 2006 and January 2008.
      Chronic venous disease patients consisted of 22 postthrombotic patients and 10
      with 1 degrees CVI. Arterial inflow was measured at rest using venous occlusion
      plethysmography and after induced arterial inflow using postocclusive reactive
      hyperemia (PORH). Volume changes were recorded with volume plethysmography. A
      minimum of 10 minutes elapsed between the resting and PORH measurements of
      arterial inflow. RESULTS: Resting arterial inflow was greater in patients with 1
      degrees CVI when compared to normal patients (2.81 vs 1.26, P = .008) and to
      patients with postthrombotic venous disease (2.81 vs 1.13, P = .03). There was a
      7.3-fold increase in maximal arterial inflow in normal patients during PORH
      versus a 4.8-fold increase in patients with postthrombotic venous disease (P =
      .015). Patients with 1 degrees CVI had a marked attenuation of maximal arterial
      inflow during hyperemic limb challenge, demonstrating only a twofold increase
      relative to their baseline resting arterial inflow (P = .08). CONCLUSION:
      Increases in arterial inflow during a hyperemic limb challenge are less robust in
      patients with postthrombotic venous disease than in normal volunteers. These data
      suggest that the pain of venous claudication may in part be due to a diminished
      arterial inflow response.

PMID- 18639425
TI  - Endovascular repair of traumatic thoracic aortic disruptions with "stacked"
      abdominal endograft extension cuffs.
AB  - OBJECTIVE: Endovascular stent graft repair of a traumatic thoracic aortic
      disruption (TTAD) is rapidly becoming an accepted alternative to open surgical
      repair. The use of currently approved thoracic stent grafts especially in younger
      patients with small, "steep," tapered aortas, remains a concern due to the acute
      thoracic endograft collapse and enfolding. The objective of this study, the
      largest report to date, was to evaluate the mid-term results of TTAD treated with
      abdominal aortic "stacked" extension cuffs, with follow-up extending to 41
      months. METHODS: Thirty-one patients with multi-system trauma (age range, 15 to
      61; mean 31.4 years) were seen after motor vehicle accidents between January 1,
      2003 and July 1, 2007. Chest x-ray findings warranted thoracic CT scans, which
      revealed disruptions of the thoracic aorta. Intra-operative arteriograms in all
      patients and intravascular ultrasound (IVUS) (n = 17) delineated the extent of
      the aortic injuries. The aortic length from the subclavian artery to the injury
      averaged 2.5 cm (range, 1.5 to 4.0 cm). The repairs were performed with Gore
      (W.L. Gore & Associates, Flagstaff, Ariz) (n = 15), Aneuryx (Medtronic, Santa
      Rosa, Calif) (n = 15), and Zenith (Cook, Inc., Bloomington, Ind) (n = 1) Aortic
      Extension Cuffs. A femoral artery approach was used in 27 patients and a supra
      inguinal retroperitoneal iliac approach in four. All patients underwent thoracic
      CT scans during follow-up. RESULTS: In all patients, the stent-graft cuffs
      successfully excluded the TTAD: 21 patients had 2 cuffs, 9 had 3 cuffs, and 1 had
      4 cuffs. The aorta adjacent to the injury mean diameter was 18.5 mm (range, 17-24
      mm). No subclavian arteries were covered. Two patients required an additional
      cuff for exclusion of the Type I endoleaks at the distal attachment site within 6
      weeks of initial endograft repair. There were no procedure-related deaths; 2
      patients died of other injuries. At follow-up, extending to 41 months (range, 3
      to 41 months), two pseudo-aneurysms occurred which required open operative
      repair: 1 due to infection (4 months) and a leaking pseudoaneurysm (14 months). A
      CT scan in all other survivors demonstrated no device-related complications,
      endoleaks, or cuff migrations. CONCLUSION: Stent-graft repair of TTAD is
      technically feasible. The technique of "stacked" aortic cuffs provides an
      acceptable option when urgent therapy is needed, when patients are deemed high
      risk for open operative repair, or until thoracic endografts are designed which
      can safely treat focal, smaller aortic diameter injuries.

PMID- 18639426
TI  - Cardiovascular risk profile and outcome of patients with abdominal aortic
      aneurysm in out-patients with atherothrombosis: data from the Reduction of
      Atherothrombosis for Continued Health (REACH) Registry.
AB  - OBJECTIVE: Datasets regarding patients with abdominal aortic aneurysm (AAA) have
      almost universally been restricted to single geographic regions. We aimed to
      obtain data on the risk factor profile and cardiovascular (CV) co-morbidity among
      multi-ethnic patients with known AAA in the global REACH (REduction of
      Atherothrombosis for Continued Health) Registry. METHODS: The REACH Registry is
      an international, prospective, observational out-patient registry enrolling out
      patients >/=45 years of age with established coronary artery disease (CAD),
      cerebrovascular disease (CVD) or peripheral arterial disease (PAD) or with at
      least three atherothrombotic risk factors. This report includes observations
      pertaining to 68,236 out-patients enrolled in 44 countries. MAIN OUTCOME
      MEASURES: Gender, ethnic origin, CV risk factors, established atherosclerotic
      disease (CAD, CVD and PAD) at baseline, and CV outcome events at 1-year were
      compared in patients with and without AAA. RESULTS: An AAA was reported in 1722
      (2.5%) of 68,236 out-patients enrolled in the REACH Registry. Older age (73 +/- 8
      vs 68 +/- 10, P < .0001), male gender (81% vs 63%, P < .0001), White ethnicity
      (79% vs 67%, P < .0001) and a history of smoking (81% vs 55%, P < .0001) were
      independently related to the diagnosis of AAA. There was a weaker association
      with hypertension or hypercholesterolemia, and an inverse relation with diabetes.
      Fatal and non-fatal coronary and cerebrovascular event rates were not different
      between the AAA and non-AAA cohorts, but individuals with AAA suffered increased
      rates of other cardiovascular deaths (1.39% vs 0.94%, P = .0135),
      hospitalizations for atherothrombotic events (14.1% vs 9.3%, P < .0001) due to
      increased rates of revascularization procedures, and new or worsening PAD (3.7%
      vs 1.3%, P < .0001) at 1-year follow-up. CONCLUSION: This study, the largest
      published to date, presents the CV risk profile and outcome of patients with an
      established diagnosis of AAA from a cohort of patients with either overt
      manifestations of CV disease or multiple risk factors, and further defines these
      patients in a multi-ethnic, global context.

PMID- 18639427
TI  - Common femoral artery occlusive disease: contemporary results following surgical
      endarterectomy.
AB  - OBJECTIVE: Proliferation of endovascular techniques with perceived reduction in
      treatment morbidity repetitively question the precept that surgical
      endarterectomy is the preferred treatment for occlusive disease of the common
      femoral artery (CFA). This study details a contemporary experience with common
      femoral endarterectomy (CFE) with and without concomitantly performed
      endovascular therapies. METHODS: Technical, hemodynamic, and clinical success of
      CFE performed between 2002 and 2005 were determined according to the Society of
      Vascular Surgery reporting standards. Primary and assisted patencies of the CFA
      segment, freedom from reintervention in the ipsilateral limb, and survival were
      assessed using Kaplan-Meier life-table analysis. Multivariate analysis was
      performed to evaluate factors associated with patency and survival. RESULTS: CFE
      was performed on 65 limbs in 58 patients (mean age 71 +/- 10; male 77%; diabetes
      28%; creatinine >/= 1.5 mg/dL 19%). Forty-four cases (68%) were performed for
      claudication, and 21 cases (32%) for critical limb ischemia. Thirty-seven cases
      (57%) were performed as a hybrid procedure wherein concomitant endovascular
      interventions were performed. Twenty iliac (TASC II A-30%; B-35%; C-20%; D-15%)
      and 25 femoropopliteal (TASC II A-24%; B-60%; C-12%; D-4%) lesions were treated.
      Technical success was achieved in 100% of the cases. Hemodynamic success was
      achieved in 95% of the cases with mean postoperative increase in ankle-brachial
      index (ABI) of 0.24 +/- 0.24. All but one patient (98.5%) had improvement in
      symptoms and/or ABI. Average hospital stay was 3.2 days (range 1-12 days). There
      were 3 (5%) major complications requiring reintervention (early failure secondary
      to untreated inflow lesion, hematoma, and wound infection), six (9%) minor
      complications which were treated conservatively (five wound infections, one lymph
      leak), and no perioperative mortality. With a mean follow-up period of 27 months
      (range 1-58 months), 1- and 5-year primary patencies were 93% and 91%,
      respectively. Assisted patency was 100% at both time points. There was no
      difference in patencies between CFE performed alone or as a hybrid procedure.
      Multivariate analysis showed congestive heart failure (CHF) as the only predictor
      of primary failure (odds ratio [OR] 18.5 [2.6-142.9]; P = .004). Freedom from
      reintervention in the ipsilateral limb was 82% at 1 year and 78% at 5 years, with
      CHF again as the only predictor of reintervention (OR 5.3 [1.4-19.6]; P =.012).
      Survival was 89% at 1 year and 70% at 5 years. There were no amputations.
      CONCLUSIONS: These data suggest CFE should remain the standard of care for
      occlusive disease of the CFA. Its safety and efficacy establish a standard for
      comparison with emerging endovascular therapies.

PMID- 18639428
TI  - Efficacy of duplex ultrasound surveillance after infrainguinal vein bypass may be
      enhanced by identification of characteristics predictive of graft stenosis
      development.
AB  - OBJECTIVE: Controversy regarding the efficacy of duplex ultrasound surveillance
      after infrainguinal vein bypass led to an analysis of patient and bypass graft
      characteristics predictive for development of graft stenosis and a decision of
      secondary intervention. METHODS: Retrospective analysis of a contemporary,
      consecutive series of 353 clinically successful infrainguinal vein bypasses
      performed in 329 patients for critical (n = 284; 80%) or noncritical (n = 69;
      20%) limb ischemia enrolled in a surveillance program to identify and repair
      duplex-detected graft stenosis. Variables correlated with graft stenosis and
      bypass repair included: procedure indication, conduit type (saphenous vs
      nonsaphenous vein; reversed vs nonreversed orientation), prior bypass graft
      failure, postoperative ankle-brachial index (ABI) < 0.85, and interpretation of
      the first duplex surveillance study as "normal" or "abnormal" based on peak
      systolic velocity (PSV) and velocity ratio (Vr) criteria. RESULTS: Overall, 126
      (36%) of the 353 infrainguinal bypasses had 174 secondary interventions
      (endovascular, 100; surgery, 74) based on duplex surveillance; resulting in 3
      year Kaplan-Meier primary (46%), assisted-primary (80%), and secondary (81%)
      patency rates. Characteristics predictive of duplex-detected stenosis leading to
      intervention (PSV: 443 +/- 94 cm/s; Vr: 8.6 +/- 9) were: "abnormal" initial
      duplex testing indicating moderate (PSV: 180-300 cm/s, Vr: 2-3.5) stenosis (P <
      .0001), non-single segment saphenous vein conduit (P < .01), warfarin drug
      therapy (P < .01), and redo bypass grafting (P < .001). Procedure indication,
      postoperative ABI level, statin drug therapy, and vein conduit orientation were
      not predictive of graft revision. The natural history of 141 (40%) bypasses with
      an abnormal first duplex scan differed from "normal" grafts by more frequent (51%
      vs 24%, P < .001) and earlier (7 months vs 11 months) graft revision for severe
      stenosis and a lower 3-year assisted primary patency (68% vs 87%; P < .001). In
      52 (15%) limbs, the bypass graft failed and 20 (6%) limbs required amputation.
      CONCLUSIONS: The efficacy of duplex surveillance after infrainguinal vein bypass
      may be enhanced by modifying testing protocols, eg, rigorous surveillance for
      "higher risk" bypasses, based on the initial duplex scan results and other
      characteristics (warfarin therapy, non- single segment saphenous vein conduit,
      redo bypass) predictive for stenosis development.

PMID- 18639429
TI  - Clinical validation of a molecular assay for intra-operative detection of
      metastases in breast sentinel lymph nodes.
AB  - BACKGROUND: In breast cancer patients, the status of the sentinel lymph nodes
      (SLNs) has been shown to accurately reflect the presence of metastases in the
      axillary lymph nodes (ALNs). Intra-operative SLN evaluation by frozen section
      histology may miss positive cases, leading to a second surgery for complete ALN
      dissection. Permanent section histology itself has tissue sampling limitations
      and is partially dependent on pathologist expertise. METHODS: A prospective study
      (N=78) was conducted in our institution to validate a new intra-operative
      molecular assay, the GeneSearch breast lymph node (BLN) assay. This assay
      quantifies the expression of mammaglobin and cytokeratin-19 genes using
      quantitative RT-PCR technology to determine SLN status. Fresh SLN sections (2 mm
      thick) were analyzed alternatively by BLN assay or post-operative histology
      (haematoxylin-eosin and immunohistochemistry). The subject was considered
      positive when histology revealed a focus >0.2 mm. RESULTS: BLN assay results
      corroborated with histologic results in 75 out of 78 patients for an overall
      agreement of 96%, a sensitivity of 92%, and a specificity of 97%. The positive
      and negative predictive values of the BLN assay were of 86% (12/14) and 98%
      (63/64), respectively. Interestingly, a statistically significant correlation was
      observed between the metastases' histologic size and both assay markers'
      expression levels as represented by cycle time to positivity (rho > or = 0.71,
      all p<0.0001). CONCLUSIONS: The performance of the BLN assay in identifying nodal
      metastases >0.2 mm was similar to that of permanent section histology, with the
      added advantages of an objective and rapid output that could be used for intra
      operative decision to remove additional ALN.

PMID- 18639430
TI  - Metal-on-metal total hip arthroplasty.
AB  - Although metal-on-metal total hip arthroplasty (MOM THA) has been used for over 3
      decades, substantial improvements in manufacturing and design have led to
      improved durability with modern implants. Reported advantages of the use of MOM
      THA include very low wear and subsequent osteolysis, increased range of motion to
      impingement secondary to the availability of larger diameter femoral heads, and
      the potential to monitor implant performance by serial assessment of metal ion
      levels. Clinical results of both first-generation and second-generation MOM THA
      have revealed good survivorship and a low incidence of osteolysis. Although the
      advantages of low wear and increased range of motion have made MOM THA an
      attractive bearing surface option, more widespread use of MOM bearing surfaces
      has been tempered with concern for increased metal ion levels and
      hypersensitivity reactions.

PMID- 18639431
TI  - Eleven years of experience with metal-on-metal hybrid hip resurfacing: a review
      of 1000 conserve plus.
AB  - Hip resurfacing is currently the fastest growing hip procedure worldwide. We
      reviewed 1000 hips in 838 patients who received a Conserve Plus (Wright Medical
      Technology, Inc., Arlington, Tenn) resurfacing at a single institution. The mean
      age of the patients was 50.0 years with 74.7% male. The hips were resurfaced
      irrespective of femoral defect size or etiology. The mean follow-up was 5.6 years
      (range, 1.1-11.0 years). All clinical scores improved significantly (P < .05).
      There was no acetabular component loosening. Ten were converted to total hip
      arthroplasty for femoral neck fracture, 20 for femoral loosening, 2 for sepsis,
      and 1 for recurrent subluxations. The 5-year survivorship was 95.2% with no
      failures in hips implanted since 2002. Short-term failures can be prevented.
      First-generation surgical technique and a low body mass index were the most
      important risk factors for the procedure. Improvements in bone preparation
      significantly increased prosthetic survival in hips with risk factors for
      failure.

PMID- 18639432
TI  - Metal hypersensitivity: can it mimic infection?
AB  - Metal hypersensitivity leading onto hardware rejection is reported as a rare
      phenomenon. If not suspected, it can be a harrowing experience for the patient
      because it can lead to a seemingly never-ending cycle of tests and procedures.
      This case highlights the fact that although metal hypersensitivity is rare, it
      should be included in the differential once infection has been excluded.

PMID- 18639433
TI  - Fixed-angle screws vs standard screws in acetabular prosthesis fixation: a
      cadaveric biomechanical study.
AB  - Secure fixation of acetabular components in total hip arthroplasty can be
      challenging. The purpose of this study was to perform biomechanical analysis of
      cup fixation strength using fixed-angle vs standard screw fixation. Multihole,
      porous-backed acetabular prostheses were implanted in both acetabuli of 8
      cadaveric pelves using standard press-fit techniques. Fixed-angle screws were
      used on the left side, and standard cancellous screws were used in the right. The
      use of fixed-angle screws enhanced acetabular fixation substantially under
      subfailure cyclic loading conditions and load-to-failure. The triradiate screw
      configuration increases the bending moment required to fail the specimens as
      well. Fixed-angle screws may be useful for achieving rigid fixation of acetabular
      prostheses in challenging clinical scenarios.

PMID- 18639434
TI  - Caveat arthroplasty.
AB  - Caveat arthroplasty is arthroplasty undertaken to treat a presumed nonneoplastic
      disorder, which is later determined to be secondary to an extraarticular tumor.
      We identified 6 patients who had caveat arthroplasty before referral to our
      orthopedic oncology center. Three patients had completed arthroplasties at an
      average of 29 weeks before discovery of a neoplasm. Three arthroplasties were
      aborted after a neoplasm was discovered intraoperatively. Prearthroplasty
      radiographs of 4 patients were reviewed, all demonstrating evidence of
      malignancy. Caveat arthroplasty may be avoided if malignancy is considered
      preoperatively, particularly in patients with atypical symptoms, histories of
      cancer, and rapid periarticular bone loss. If a neoplasm is discovered
      intraoperatively, the arthroplasty should be aborted. Patients in whom malignancy
      is suspected should be referred to a musculoskeletal oncologist.

PMID- 18639435
TI  - Variability in hip range of motion on clinical examination.
AB  - The goal of this study was to determine the interobserver and intraobserver
      reliability of physical examination in determining hip range of motion. Twenty
      normal hips, 21 hips with osteoarthritis, and 21 hips of patients more than 12
      months after a total hip arthroplasty were examined for visual passive range of
      motion. These 62 hips were examined by 2 experienced surgeons and by 3 trainees.
      The 2 experienced examiners repeated their clinical examinations in 19 patients
      to determine the intraobserver reliability. Intraclass correlation coefficients
      (ICCs) indicated moderate interobserver agreement in estimates of clinical hip
      motion (ICC for hip flexion, 0.56 +/- 0.12; for hip abduction, 0.48 +/- 0.13).
      Intraclass correlation coefficients also suggest only moderate intraobserver
      reliability in measurements of hip motion (ICC for hip flexion, 0.62 +/- 0.14;
      hip abduction, 0.44 +/- 0.20). More reliable and accurate methods are needed to
      measure clinical hip motion before and after total hip arthroplasty.

PMID- 18639436
TI  - Complex regional pain syndrome after infliximab infusion.

PMID- 18639437
TI  - Utility of the RBANS in detecting cognitive impairment associated with
      Alzheimer's disease: sensitivity, specificity, and positive and negative
      predictive powers.
AB  - Although initially developed as a brief dementia battery, the Repeatable Battery
      for the Assessment of Neuropsychological Status (RBANS) has not yet demonstrated
      its sensitivity, specificity, and positive and negative predictive powers in
      detecting cognitive impairment in patients with Alzheimer's disease (AD).
      Therefore, the current study examined the clinical utility of the RBANS by
      comparing two age-, education-, and gender-matched groups: patients with AD
      (n=69) and comparators (n=69). Significant differences (p<0.001) were observed on
      the RBANS Total score, all 5 Indexes, and all 12 subtests, with patients
      performing worse than the comparison participants. An optimal balance between
      sensitivity and specificity on RBANS scores was obtained when cutoffs of one and
      one and a half standard deviations below the mean of the comparison sample were
      implemented. Areas under the Receiver Operating Characteristic curves for all
      RBANS Indexes were impressive though Immediate and Delayed Memory Indexes were
      excellent (0.96 and 0.98, respectively). Results suggest that RBANS scores yield
      excellent estimates of diagnostic accuracy and that the RBANS is a useful
      screening tool in detection of cognitive deficits associated with AD.

PMID- 18639438
TI  - Development and application of a neuroinformatics environment for neuroscience
      and neuroethology.
AB  - Insect brains are excellent models for analyzing neuronal function in moderately
      complex central nervous systems due to the vast potential they offer for
      revealing the intricate details of the workings of a biological neural network.
      For a systematic approach to understanding neuronal mechanisms, it is important
      to integrate research results from various fields, such as morphology, physiology
      and immunohistochemistry. We are developing a database system, the Bombyx Neuron
      Database (BoND) for assembling and sharing experimental and analytical data. The
      system is designed and developed based on experimental data, mostly obtained from
      intracellular recordings. A new WWW technology, CMS (Content Management System),
      was implemented in our system. That is, PHP-based CMS, XOOPS, provides several
      functions for web-based database management, for instance, user accounting, web
      page designing and data backup. The BoND was developed by our original database
      module of XOOPS, in order to deal with electrophysiological and anatomical data.
      Research resources from various fields are combined in the database for realizing
      a conjunction of experiments and analysis, which will assist progress in
      understanding neural network mechanisms as a virtual laboratory.

PMID- 18639439
TI  - An evaluation of patient-reported outcomes found computerized adaptive testing
      was efficient in assessing stress perception.
AB  - OBJECTIVES: This study aimed to develop and evaluate a first computerized
      adaptive test (CAT) for the measurement of stress perception (Stress-CAT), in
      terms of the two dimensions: exposure to stress and stress reaction. STUDY DESIGN
      AND SETTING: Item response theory modeling was performed using a two-parameter
      model (Generalized Partial Credit Model). The evaluation of the Stress-CAT
      comprised a simulation study and real clinical application. A total of 1,092
      psychosomatic patients (N1) were studied. Two hundred simulees (N2) were
      generated for a simulated response data set. Then the Stress-CAT was given to
      n=116 inpatients, (N3) together with established stress questionnaires as
      validity criteria. RESULTS: The final banks included n=38 stress exposure items
      and n=31 stress reaction items. In the first simulation study, CAT scores could
      be estimated with a high measurement precision (SE<0.32; rho>0.90) using 7.0+/
      2.3 (M+/-SD) stress reaction items and 11.6+/-1.7 stress exposure items. The
      second simulation study reanalyzed real patients data (N1) and showed an average
      use of items of 5.6+/-2.1 for the dimension stress reaction and 10.0+/-4.9 for
      the dimension stress exposure. Convergent validity showed significantly high
      correlations. CONCLUSIONS: The Stress-CAT is short and precise, potentially
      lowering the response burden of patients in clinical decision making.

PMID- 18639440
TI  - External lymphatic fistula after intra-abdominal lymphadenectomy for cancer.
      Treatment with total parenteral nutrition and somatostatin.
AB  - OBJECTIVE: External lymphatic fistula or chyloperitoneum after intra-abdominal
      lymphadenectomy may present challenging problems. In the absence of definite
      guidelines the choice of treatment is often empirical, with unpredictable
      effectiveness, and the reporting of new cases may broaden the available
      experience. METHODS: We describe two cases. One patient had high-output external
      fistula (1300 mL/d) after para-aortic lymphadenectomy for metastatic lymph nodes.
      The fistula became fully evident at postoperative day 4, with resumption of an
      oral diet, on the basis of a 1300-mL/d output of white milky fluid from an
      abdominal drainage. Oral feeding was interrupted and total parenteral nutrition
      was started; this was transiently associated with octreotide administration,
      subsequently replaced by somatostatin. The second patient had a low-output
      fistula (350 mL/d) after liver resection and lymphadenectomy for
      cholangiocarcinoma and underwent treatment with total parenteral nutrition and
      somatostatin. RESULTS: In the first case the lymphatic fistula healed in just
      less than 3 wk, with the patient constantly remaining in very good condition,
      without secondary complications. In the second case the low-output fistula healed
      more rapidly. CONCLUSION: Interruption of oral feeding with total parenteral
      nutrition and continuous somatostatin infusion was an effective treatment in both
      patients with an intra-abdominal lymphatic leak.

PMID- 18639441
TI  - Differences in ictal hyperperfusion of limbic-related structures between mesial
      temporal and neocortical epilepsy.
AB  - BACKGROUND: Ictal propagation to the cortical and subcortical structures is well
      known in mesial temporal epilepsy (MTE) and neocortical epilepsy (NE). We
      analyzed the ictal changes of regional blood flow in limbic-related cortical and
      subcortical structures to evaluate the differences in ictal propagation patterns
      between MTE and NE. METHODS: In 65 patients (mean age, 29.1+/-10.83 years) with
      intractable MTE (n=46) or NE (n=19), ictal 99m-Tc ethyl cystinate dimer SPECT was
      performed. A subtracted ictal SPECT coregistered to MRI images was obtained in
      each patient. The patterns of subtracted ictal hyperperfusion in the limbic,
      paralimbic and subcortical structures in patients with MTE and NE were compared.
      RESULTS: The ictal hyperperfusion of the amygdala, hippocampus, temporal pole and
      insula were significantly higher in MTE (P<0.01), but cingulate and orbitofrontal
      hyperperfusion were not. A significant difference in striatal ictal
      hyperperfusion between the MTE and NE group was found (P=0.035). Ictal
      hyperperfusion of NE was greater in the superior part (P=0.011), whereas that of
      MTE was greater in the inferior and middle parts. CONCLUSIONS: These findings
      suggest that the ictal propagation of MTE may differ from that of NE via
      different pathways not only in the cortical regions but also in the subcortical
      structures.

PMID- 18639442
TI  - Reduced plasma nitric oxide metabolites before and after antipsychotic treatment
      in patients with schizophrenia compared to controls.
AB  - BACKGROUND: Nitric oxide (NO) is believed to have a role in the pathophysiology
      of schizophrenia. We examined plasma levels of NO metabolites in patients with
      schizophrenia and normal controls. We also determined the impact of 6-week
      risperidone treatment on circulating NO metabolites in patients with
      schizophrenia. METHOD: Plasma NO metabolite (NO(x)) levels were measured in 55
      schizophrenia patients before and after 6-week treatment with risperidone and in
      55 normal controls. Severity of schizophrenia and response to treatment were
      assessed with the positive and negative syndrome scale (PANSS) for schizophrenia.
      NO(x) levels were estimated by the Griess method. RESULTS: Pre-treatment plasma
      NO(x) levels in schizophrenia patients (8.97+/-6.74 micromol/L) were lower than
      those of normal controls (14.51+/-6.30 micromol/L) (p<0.01). Schizophrenia
      patients had lower post-treatment NO(x) levels (10.99+/-8.31 micromol/L) than
      those of normal controls (p<0.01). There was marginal significant change between
      plasma NO(x) levels before and after 6-week treatment (p=0.056). Moreover, in 37
      treatment responders (> or = 30% improvement in PANSS score), post-treatment
      plasma NO(x) significantly increased in comparison to pre-treatment NO(x)
      (p=0.028). CONCLUSIONS: Plasma levels of NO(x) in patients with schizophrenia
      were significantly lower than normal controls both before and after the
      treatment. Our findings suggest that the improvement of psychiatric symptoms can
      lead to partially normalize a deficiency of NO after treatment in schizophrenia
      patients. Our findings support the hypothesis that the NO system is dampened in
      schizophrenia.

PMID- 18639443
TI  - Exploring the prokaryotic virosphere.
AB  - The world of prokaryotic viruses, including the "traditional" bacteriophages and
      the viruses of Archaea, is currently in a period of renaissance, brought about
      largely by our new capabilities in (meta)genomics and by the isolation of diverse
      novel virus-host systems. In this review, we highlight some of the directions
      where we believe research on the prokaryotic virosphere will lead us in the near
      future.

PMID- 18639444
TI  - [Status of iodine nutrition of children until 1 year: consequences on the thyroid
      function].
AB  - INTRODUCTION: Iodine deficiency remains a major public health problem mainly in
      least-developed countries but also in many industrialized countries. OBJECTIVES:
      The present study aimed at: (1) evaluating the status of iodine nutrition of
      children until 1 year in the North region of France; (2) studying risk factors
      for iodine deficiency; (3) evaluating relationship between iodine deficiency and
      thyroid disorders. PATIENTS AND METHODS: This prospective study was conducted
      between 1st january and 31st May 2005 in the children's hospital of Lille (North
      of France) and all hospitalized children until the age of 1 year were enrolled.
      Urinary iodine assessment was obtained for 95 (83%) of the 114 infants
      hospitalized during the study period and TSH value was also determined in 57
      (60%) of these 114 infants. RESULTS: Median urinary iodine concentration was 328
      microg/L (range: 12-1580). Twenty-four (25%) of 95 infants had a high urinary
      iodine excretion (urinary iodine greater than 400 microg/L). Nineteen (20%) of
      the 95 infants were iodine deficient (urinary iodine less than 100 microg/L):
      severe iodine deficiency (less than 20 microg/L; n=5; 5%), moderate iodine
      deficiency (20-49 microg/L; n=6; 6%), mild iodine deficiency (50-99 microg/L;
      n=8; 8%). No relationship was found between iodine status and the following data:
      age, sex, familial thyroid disease history, term and type of delivery,
      nutritional status, type of feeding at inclusion, chronic disease, familial
      socioeconomic status. TSH value was high (greater than 5 microU/mL) in 7 (12%) of
      the 57 infants. Only 1 of these 7 infants was iodine deficient. Only 1 of the 19
      infants with iodine deficiency had a high TSH value. CONCLUSIONS: Iodine status
      is not optimal in our population of hospitalized children until the age of 1
      year. There is no clear relationship between iodine status and thyroid function.

PMID- 18639445
TI  - [Urinary tract infection and antibiotics: oral or intravenous route?].
AB  - Management of acute pyelonephritis has long been discussed. The French drug
      agency (Agence Francaise de Securite Sanitaire des Produits de Sante [AFSSAPS])
      has published guidelines for clinical practice in 2007: two to four days of
      initial parenteral antibiotic therapy followed by oral antibiotics, for a total
      duration of 10 to 14 days. However, recent data are conflictable and oral
      antibiotic therapy may be sufficient in some cases. Clinical trials on oral
      therapy of acute pyelonephritis in selected groups of children are currently
      ongoing. We suggest following AFSSAPS recommendations in clinical practice until
      the results of such trials become available. In the future, we can speculate that
      antibiotic therapy may be reduced in some low risk patients, keeping in mind that
      around 15% of children with acute pyelonephritis will develop renal scars which
      may lead to hypertension and microalbuminuria in adulthood.

PMID- 18639446
TI  - Establishment of a bioassay model for lung cancer chemoprevention initiated with
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice.
AB  - AIMS: In order to prevent lung cancer development in people at high risk,
      identification of chemopreventive agents may be important. The present study was
      conducted to establish a bioassay model for this purpose. In particular, the time
      course of 4-(methylnitrosamno)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor
      development was examined to determine the most appropriate shortest period to
      assess effects of test agents, with 8-methoxypsoralen (8-MOP) as a typical
      example. METHODS: A total of 124 mice were separated into two groups (Group A: 60
      mice, Group B: 64 mice), pretreated with 100ppm 8-MOP (Group A) or basal diet
      (Group B) for 3 days before receiving single doses of NNK (2mg/0.1ml saline/mouse
      i.p.) on days 0 and 7. Subgroups of 15 mice of each group were then sacrificed
      after 8, 10, 12, and 16 weeks. RESULTS: Microscopically, the earliest time point
      when significant differences in data for hyperplasia, adenoma and hyperplasia and
      adenoma could be detected was 12 weeks. A trend was noted for 8-MOP to reduce
      adenomas to a greater extent than hyperplasia. DISCUSSION: In conclusion, the
      results of this study showed that the double i.p. treatment with NNK and 12 weeks
      duration are effective for detection of lung cancer chemoprevention in our A/J
      mouse lung tumorigenesis model.

PMID- 18639447
TI  - Sublethal and lethal toxicity in juvenile Senegal sole (Solea senegalensis)
      exposed to copper: a preliminary toxicity range-finding test.
AB  - Static bioassay test for acute toxicity of copper in Senegal sole juveniles
      (Solea senegalensis) was conducted. The 96h LC(50) value of metal was found to be
      0.32mg/L Cu. The intensity of histological alterations was increased gradually
      with the copper concentration and the exposure time. Numerous aneurysms,
      hypertrophy, hyperplasia and fusion of the lamellar epithelium in gills and a
      disorganization of the hepatic parenchyma and vacuolization in liver were common
      lesions in S. senegalensis juveniles exposed to copper. The results of the study
      indicate the sensitivity of juvenile S. senegalensis to copper (II), the
      persistence of sublethal effects and histology as a tool capable of revealing the
      sublethal effects of heavy metals on the environment and aquatic biota.

PMID- 18639448
TI  - Antler stiffness in caribou (Rangifer tarandus): testing variation in bone
      material properties between males and females.
AB  - Vertebrate bones, including deer antler, often exhibit variation in their
      mechanical properties that corresponds to differences in the functional demands
      they encounter. Among deer, antlers are found in both males and females only in
      caribou (Rangifer tarandus). Several differences between male and female R.
      tarandus in behavior and physiology might subject their antlers to differing
      demands, potentially making divergence of antler material properties between the
      sexes advantageous. Alternatively, antler material properties might not differ
      between male and female R. tarandus because both sexes are members of the same
      species, and the properties of their antlers could, therefore, have emerged under
      similar pressures and constraints through evolution. To test for sexual
      dimorphism in antler material properties, we compared the stiffness (Young's
      modulus of elasticity) of antler specimens from male and female caribou using
      three-point bending tests. Despite behavioral and physiological differences
      between males and females, stiffness values did not differ significantly between
      the sexes in caribou, with a mean (+/-S.E.) stiffness of 5.8+/-0.4 GPa across all
      specimens. This value differed by less than 10% from the values published for R.
      tarandus specimens of unknown sex, verifying the comparability of bone material
      property data collected across multiple studies, and lending confidence to recent
      analyses of the evolution of antler stiffness in deer that have drawn on
      literature data.

PMID- 18639451
TI  - The detection and significance of melanoma micrometastases in sentinel nodes.
AB  - Sentinel node (SN) biopsy in melanoma patients is an accurate and minimally
      invasive method of staging and determining prognosis in patients with early-stage
      disease, and of identifying those patients who may benefit from complete regional
      lymph node dissection. Careful identification, removal and pathological
      assessment of SNs is critical to the accuracy of the technique and deficiencies
      in any of these steps may result in a false-negative biopsy. Pathologists should
      examine multiple sections from each SN, stained routinely with haematoxylin-eosin
      and immunohistochemically for melanoma-associated antigens. However, the most
      appropriate staining and sectioning protocol is not clear from the available
      evidence. While it appears that more extensive sectioning protocols detect more
      melanoma, failure rates and false-negative rates of the procedure do not appear
      to be significantly worse than with less extensive sampling protocols.
      Micromorphometrical parameters of melanoma deposits in SNs (such as their size,
      maximal tumour penetrative depth, microanatomical location and percentage nodal
      cross-sectional area) have been shown to be predictive of regional non-SN
      involvement and of clinical outcome. Classifying and measuring these parameters
      can be difficult, depending on the nature and distribution of the tumour deposits
      in the SN. Because the positive SNs have been removed in all patients included in
      studies assessing the clinical significance of tiny SN melanoma micrometastases,
      the likely therapeutic effect of the SN biopsy itself and/or any complete lymph
      node dissection, as well as lead time bias, are important confounding factors
      that must be considered when interpreting these studies. Limited data from some
      retrospective studies with relatively short follow-up suggest that some melanoma
      metastases may not be clinically relevant, but other studies imply a likely
      clinical significance of even very small SN metastases. Until there is
      unequivocal evidence from prospective randomised clinical trials with long term
      follow-up for the prognostic significance (or lack thereof) of very small SN
      tumour deposits, it is probably prudent to treat patients with such deposits as
      SN-positive.

PMID- 18639450
TI  - A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan,
      5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a
      Hellenic Cooperative Oncology Group Study.
AB  - The primary objective was to compare the 3-year survival of rectal cancer
      patients randomised postoperatively to irinotecan (IRI), Leucovorin (LV) and
      bolus 5-fluorouracil (5FU) or LV-bolus 5FU with radiotherapy. Secondary
      objectives included disease-free survival, local relapse and toxicity. The study
      included 321 eligible patients. The treatment consisted of weekly administration
      of IRI 80 mg/m(2) intravenously (IV), LV 200 mg/m(2) and 5FU 450 mg/m(2) bolus
      (arm A) versus LV 200 mg/m(2) and 5FU 450 mg/m(2) IV bolus (arm B). One cycle
      included four infusions and treatment was continued for a total of six cycles.
      The first cycle was followed by pelvic irradiation plus 5FU. There were no
      differences between the arms in 3-year overall, disease-free and local relapse
      free survival. Grades 3 and 4 toxicity was similar in both the arms with the
      exception of leucopaenia, neutropaenia and alopecia, which were higher in the IRI
      arm. IRI added to adjuvant radiochemotherapy with LV and bolus 5FU was not shown
      to improve survival, whereas the incidence of severe leucopaenia was
      significantly higher in the IRI arm.

PMID- 18639449
TI  - The killer's kiss: the many functions of NK cell immunological synapses.
AB  - Natural killer (NK) cells comprise a subset of lymphocytes involved in protection
      against microbial pathogens and tumors. NK cells recognize host cells that are
      missing MHC class I molecules and eliminate them through localized delivery of
      lytic granules. The majority of NK cell effector functions require direct cell-to
      cell contact. Binding to a target cell is accompanied by creation of complex
      structures at the cell-cell interface known as immunological synapses. Recent
      studies have contributed immensely to the characterization of several types of NK
      cell immunological synapses and understanding of the variety of processes
      originating at this intriguing place. The emerging picture illustrates NK cell
      immune synapses as the sites of highly complex regulation of NK cell activity.

PMID- 18639452
TI  - Synthesis of alpha-helix mimetics with four side-chains.
AB  - The synthesis of a heterocyclic piperazine-based scaffold that mimics the i, i+4,
      i+8, i+11 side-chain projections of an alpha-helix is described. The synthesis is
      designed to be modular to allow the targeting of a range of protein-protein
      interactions involving alpha-helices.

PMID- 18639453
TI  - Molecular modeling of a PAMAM-CGS21680 dendrimer bound to an A2A adenosine
      receptor homodimer.
AB  - The theoretical possibility of bivalent binding of a dendrimer, covalently
      appended with multiple copies of a small ligand, to a homodimer of a G protein
      coupled receptor was investigated with a molecular modeling approach. A molecular
      model was constructed of a third generation (G3) poly(amidoamine) (PAMAM)
      dendrimer condensed with multiple copies of the potent A(2A) adenosine receptor
      agonist CGS21680. The dendrimer was bound to an A(2A) adenosine receptor
      homodimer. Two units of the nucleoside CGS21680 could occupy the A(2A) receptor
      homodimer simultaneously. The binding mode of CGS21680 moieties linked to the
      PAMAM dendrimer and docked to the A(2A) receptor was found to be similar to the
      binding mode of a monomeric CGS21680 ligand.

PMID- 18639454
TI  - Exploration of a fundamental substituent effect of alpha-ketoheterocycle enzyme
      inhibitors: Potent and selective inhibitors of fatty acid amide hydrolase.
AB  - A series of C4 substituted alpha-ketooxazoles were examined as inhibitors of the
      serine hydrolase fatty acid amide hydrolase in efforts that further define and
      generalize a fundamental substituent effect on enzyme inhibitory potency. Thus, a
      plot of the Hammett sigma(m) versus -logK(i) provided a linear correlation
      (R(2)=0.90) with a slope of 3.37 (rho=3.37), that is of a magnitude that
      indicates that of the electron-withdrawing character of the substituent dominates
      its effects (a one unit change in sigma(m) provides a >1000-fold change in K(i)).

PMID- 18639455
TI  - Design and optimization of potent, selective antagonists of Oxytocin.
AB  - A novel series of Oxytocin antagonists are described. This series was identified
      through pharmacophoric overlap of in-house and literature antagonists. Subsequent
      optimization led to a series of potent, selective antagonists. Several analogues
      displayed oral bioavailability in vivo in the rat.

PMID- 18639456
TI  - Sialyl alpha(2-->3) lactose clusters using carbosilane dendrimer core scaffolds
      as influenza hemagglutinin blockers.
AB  - An efficient synthesis of a series of carbosilane dendrimers uniformly
      functionalized with sialyl alpha(2-->3) lactose (Neu5Acalpha(2-->3)Galbeta(1-
      >4)Glcbeta1-->) moieties was accomplished. The results of a preliminary study on
      biological responses against influenza virus hemagglutinin, using the sialyl
      lactose clusters showed unique biological activities on the basis of the
      structure-activity relationship according to the carbosilane scaffolds.

PMID- 18639457
TI  - Cardiac assessment of limb-girdle muscular dystrophy 2I patients: an echography,
      Holter ECG and magnetic resonance imaging study.
AB  - Mutations in the FKRP gene may be associated with cardiac involvement. The aim of
      our study was to assess myocardial involvement in patients with LGMD2I, using
      physical examination, echocardiography, resting and 24-h ambulatory
      electrocardiogram and cardiac magnetic resonance imaging, with particular
      attention to the detection of myocardial morphologic abnormalities. Patients were
      compared to matched controls. Twenty-three patients were enrolled (men 10--women
      13; 32.3+/-9.5 years). Twenty-two had the C826A gene mutation (homozygous 12,
      heterozygous 10). Nine patients had severe muscle alterations, 10 had milder
      muscle involvement and 4 had isolated exertional myoglobinuria. When compared to
      controls, LGMD2I patients had reduced left ventricular ejection fraction (50.8+/
      13.9 versus 66.6+/-3.8%, p<0.0001). Sixty percent of patients had reduced left
      ventricular ejection fraction, including 8% with severe reduced left ventricular
      ejection fraction <30%. None had significant arrhythmia. Gene mutation and the
      severity of the muscle disease were not predictive of cardiac involvement.
      Cardiac magnetic resonance imaging displayed a high prevalence of myocardial
      functional abnormalities, fatty replacement and fibrosis, among the 13 patients
      investigated. Reduced contractility and cardiac magnetic resonance imaging
      morphological abnormalities are highly prevalent in LGMD2I patients suggesting
      that all patients should be referred for cardiac evaluation.

PMID- 18639458
TI  - Bacterial polysaccharides suppress induced innate immunity by calcium chelation.
AB  - Bacterial pathogens and symbionts must suppress or negate host innate immunity.
      However, pathogens release conserved oligomeric and polymeric molecules or MAMPs
      (Microbial Associated Molecular Patterns), which elicit host defenses [1], [2]
      and [3]. Extracellular polysaccharides (EPSs) are key virulence factors in plant
      and animal pathogenesis, but their precise function in establishing basic
      compatibility remains unclear [4], [5], [6] and [7]. Here, we show that EPSs
      suppress MAMP-induced signaling in plants through their polyanionic nature [4]
      and consequent ability to chelate divalent calcium ions [8]. In plants, Ca2+ ion
      influx to the cytosol from the apoplast (where bacteria multiply [4], [5] and
      [9]) is a prerequisite for activation of myriad defenses by MAMPs [10]. We show
      that EPSs from diverse plant and animal pathogens and symbionts bind calcium. EPS
      defective mutants or pure MAMPs, such as the flagellin peptide flg22, elicit
      calcium influx, expression of host defense genes, and downstream resistance.
      Furthermore, EPSs, produced by wild-type strains or purified, suppress induced
      responses but do not block flg22-receptor binding in Arabidopsis cells. EPS
      production was confirmed in planta, and the amounts in bacterial biofilms greatly
      exceed those required for binding of apoplastic calcium. These data reveal a
      novel, fundamental role for bacterial EPS in disease establishment, encouraging
      novel control strategies.

PMID- 18639460
TI  - UnPAKing the class differences among p21-activated kinases.
AB  - The p21-activated kinases (PAKs) are signal transducers, central to many vital
      cellular processes, including cell morphology, motility, survival, gene
      transcription and hormone signalling. The mammalian PAK family contains six
      serine/threonine kinases divided into two subgroups, group I (PAK 1-3) and group
      II (PAK4-6), based on their domain architecture and regulation. PAKs functioning
      as dynamic signalling nodes present themselves as attractive therapeutic targets
      in tumours, neurological diseases and infection. The recent findings across all
      PAKs, including newly reported structures, shed light on the cellular functions
      of PAKs, highlighting molecular mechanisms of activation, catalysis and substrate
      specificity. We believe that a comprehensive understanding of the entire PAK
      family is essential for developing strategies towards PAK-targeted therapeutics.

PMID- 18639459
TI  - Changes in bicoid mRNA anchoring highlight conserved mechanisms during the oocyte
      to-embryo transition.
AB  - Intracellular mRNA localization directs protein synthesis to particular
      subcellular domains to establish embryonic polarity in a variety of organisms. In
      Drosophila, bicoid (bcd) mRNA is prelocalized at the oocyte anterior. After
      fertilization, translation of this RNA produces a Bcd protein gradient that
      determines anterior cell fates [1] and [2]. Analysis of bcd mRNA during late
      stages of oogenesis suggested a model for steady-state bcd localization by
      continual active transport [3]. However, this mechanism cannot explain
      maintenance of bcd localization throughout the end of oogenesis, when
      microtubules disassemble in preparation for embryogenesis [4] and [5], or
      retention of bcd at the anterior in mature oocytes, which can remain dormant for
      weeks before fertilization [6]. Here, we elucidate the path and mechanism of
      sustained bcd mRNA transport by direct observation of bcd RNA particle
      translocation in living oocytes. We show that bcd mRNA shifts from continuous
      active transport to stable actin-dependent anchoring at the end of oogenesis. Egg
      activation triggers bcd release from the anterior cortex for proper deployment in
      the embryo, probably through reorganization of the actin cytoskeleton. These
      findings uncover a surprising parallel between flies and frogs, as cortically
      tethered Xenopus Vg1 mRNA undergoes a similar redistribution during oocyte
      maturation [7]. Our results thus highlight a conserved mechanism for regulating
      mRNA anchoring and redeployment during the oocyte-to-embryo transition.

PMID- 18639461
TI  - A clinical review of bioabsorbable interference screws and their adverse effects
      in anterior cruciate ligament reconstruction surgery.
AB  - Bioabsorbable material screws are widely used in various surgical specialties.
      One popular application is their use as interference screws in anterior cruciate
      ligament (ACL) reconstruction surgery. Despite their routine use, a major concern
      with bioabsorbable materials in surgery has been the incidence of adverse events.
      Various case reports, series reports and studies in the past years have reported
      complications specific to the use of bioabsorbable interference screws intra
      operatively and at different time periods post operatively. The aim of this
      literature review is to summarize the clinical studies where bioabsorbable screws
      have been used in ACL reconstruction surgery and in particular to highlight any
      specific complications and adverse effects related to the use of these materials.

PMID- 18639462
TI  - Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: synthesis,
      SAR analysis, and biological activity.
AB  - A series of nitrogen-containing flavonoid analogues were designed and synthesized
      by Mannich reaction, and screened for the inhibitory activities of cyclin
      dependent kinases using a FRET-based biochemical assay method. The results showed
      that C-8 nitrogen-containing baicalein analogues 3a-3f exhibited potent
      CDK1/Cyclin B inhibitory activities. 5,6,7-Trihydroxy-8-(dimethylaminomethyl)-2
      phenyl-4H-chromen-4-one 3a, 5,6,7-trihydroxy-8-(pyrrolid inylmethyl)-2-phenyl-4H
      chromen-4-one 3b, and 5,6,7-trihydroxy-8-(piperidinylmethyl)-2-phenyl-4H-chromen
      4-one 3c (IC(50) 1.05-1.28 microM) were about sixfold more potent than baicalein
      2 (IC(50) 6.53 microM). 5,6,7-Trihydroxy-8-(morpholinomethyl)-2-phenyl-4H-chromen
      4-one 3d, 5,6,7-trihydroxy-8-(thiomorpholinomethy)-2-phenyl-4H-chrom en-4-one 3e,
      and 5,6,7-trihydroxy-8-(4-methylpiperazinylmethyl)-2-phenyl-4H-chromen-4-one 3f
      (IC(50) 0.27-0.38 microM) were about 20-fold more potent than baicalein, and were
      at the same level as flavopiridol (IC(50) 0.33 microM).

PMID- 18639463
TI  - A new monitor for routine thermal and epithermal neutron fluence rate monitoring
      in k0 INAA.
AB  - The Zr-Au set for monitoring the thermal and epithermal neutron fluence rate and
      the epithermal spectrum parameter alpha is not always practicable for routine
      application of INAA in well-thermalized facilities. An alternative set consisting
      of Cr, Au and Mo provides values for the thermal neutron fluence rate, f and
      alpha that are not significantly different from those found via the Zr-Au method
      and the Cd-covered Zr-method. The IRMM standard SMELS-II was analyzed using the
      (Au-Cr-Mo) monitor and a good agreement was obtained.

PMID- 18639464
TI  - Balloon angioplasty for pulmonary artery stenosis after lung transplantation.
AB  - We report here a successful case of balloon angioplasty for a stenosis of the
      pulmonary artery after lung transplantation. A 49-year-old patient with end stage
      diffuse bronchiectasis with sinusitis underwent bilateral living donor lobar lung
      transplantation. After treatment of postoperative right pneumothorax, a perfusion
      lung scan revealed deficient perfusion in the left lung. Pulmonary angiography
      showed a severe stenosis in the left pulmonary artery just distal to the
      anastomosis. Percutaneous balloon angioplasty improved both pulmonary perfusion
      and respiratory function.

PMID- 18639465
TI  - Maternal and cord plasma cytokine and chemokine profile in pregnancies
      complicated by asthma.
AB  - The mechanisms contributing to worsening of asthma during pregnancy have not been
      well characterized. Both asthma and pregnancy are conditions associated with a
      skewing of the immune response from T helper (Th) 1 toward a Th2 response. We
      hypothesise that worsening of asthma during pregnancy may be due to an enhanced
      production of circulating proinflammatory cytokines and chemokines and this may
      be modified by the use of inhaled glucocorticoid treatment. Peripheral blood was
      collected from asthmatic (n=35) and control non-asthmatic patients (n=13) in the
      third trimester (30-37 weeks) of pregnancy. Fetal blood was collected from the
      umbilical vein of the placenta after delivery from normal (n=24) and pregnancies
      complicated by asthma (n=24). Plasma samples were assayed for IL-6, -8, eotaxin
      and RANTES using conventional ELISA. In addition, a range of Th1 and Th2
      cytokines measured using Luminex system. There were no significant differences in
      the levels of maternal IL-6, IL-8, eotaxin and RANTES between asthmatics and
      nonasthmatics. The results of this study suggest that the presence of asthma does
      not result in an enhanced circulation of Th2 related cytokines and chemokines
      during the third trimester of pregnancy. Furthermore peripheral blood cytokine
      concentrations appear unaffected by inhaled glucocorticoid treatment. Cord plasma
      eotaxin concentrations were increased in pregnancies complicated by asthma,
      compared with control. This is the first study to show increased eotaxin
      production in the feto-placental unit of asthmatic pregnancies and may be one
      mechanism by which allergy susceptibility is increased in the offspring of
      asthmatic women.

PMID- 18639466
TI  - Monkeypox virus viral chemokine inhibitor (MPV vCCI), a potent inhibitor of
      rhesus macrophage inflammatory protein-1.
AB  - Monkeypox virus (MPV) is an orthopoxvirus with considerable homology to variola
      major, the etiologic agent of smallpox. Although smallpox was eradicated in 1976,
      the outbreak of MPV in the U.S. highlights the health hazards associated with
      zoonotic infections. Like other orthopoxviruses, MPV encodes a secreted chemokine
      binding protein, vCCI that is abundantly expressed and secreted from MPV infected
      cells. EMSA data shows vCCI efficiently binds rhesus MIP-1alpha (rhMIP-1alpha) at
      near one to one stoichiometry. In vitro chemotaxis experiments demonstrate that
      vCCI completely inhibits rhMIP-1alpha mediated chemotaxis, while in vivo
      recruitment assays in rhesus macaques using chemokine-saturated implants show a
      decrease in the number of CD14(+) cells responding to rhMIP-1alpha when vCCI is
      present, suggesting vCCI is effectively inhibiting chemokine function both in
      vitro and in vivo. More importantly, we demonstrate that vCCI can diminish the
      severity of the acute phase and completely inhibit the relapsing phase of
      experimental allergic encephalomyelitis (EAE) disease. These data represent the
      first in vitro and in vivo characterization of vCCI emphasizing its function as a
      potent inhibitor of rhMIP-1alpha. Furthermore, the ability of vCCI to inhibit
      relapsing EAE disease represents a novel therapeutic approach for treating
      chemokine-mediated diseases.

PMID- 18639467
TI  - Peptide sequence scrambling through cyclization of b(5) ions.
AB  - The CID mass spectra of the MH(+) ions and the b(5) ions derived therefrom have
      been determined for the hexapeptides YAAAAA, AYAAAA, AAYAAA, AAAYAA, and AAAAYA.
      The CID mass spectra for the b(5) ions derived from the five isomers are
      essentially identical and show abundant ion signals for nonsequence b ions. This
      result is consistent with cyclization of the b(5) ions to a cyclic pentapeptide
      before fragmentation; this cyclic peptide can open at various positions, leading
      to losses of amino acid residues that are not characteristic of the original
      amino acid sequence. These nonsequence b ions are also observed in the
      fragmentation of the MH(+) ions and increase substantially in importance with
      increasing collision energy. A comparison of the fragmentation of AAAYAA and Ac
      AAAYAA indicates that N-acetylation eliminates the cyclization of b(5) ions and,
      thus, eliminates the nonsequence ions in the CID mass spectra of both b(5) and
      MH(+) ions.

PMID- 18639470
TI  - Phase II study of intravesical therapy with AD32 in patients with papillary
      urothelial carcinoma or carcinoma in situ (CIS) refractory to prior therapy with
      bacillus Calmette-Guerin (E3897): a trial of the Eastern Cooperative Oncology
      Group.
AB  - OBJECTIVE: To assess the safety and effectiveness of AD32, a doxorubicin analogue
      with little systemic exposure when administered intravesically, in patients with
      recurrent or refractory superficial urothelial carcinoma (formerly called
      transitional cell carcinoma [TCC]), or carcinoma in situ (CIS), who have failed
      prior BCG-based immunotherapy. METHODS: Eligible patients received six weekly
      doses (800 mg) of intravesical AD32 and were evaluated at 12-week intervals for
      24 months or until date of worsening disease. Primary analysis was the proportion
      of all patients recurrence-free at 12 months. Treatment-related and GU-specific
      toxicities were also examined. All participating institutions submitted the
      protocol for Institutional Review Board (IRB) approval. RESULTS: The study was
      halted due to unavailability of study drug after accrual of 48 of a planned 64
      patients; 42 were included in the analysis. Of these, 28 (67%) were still alive
      after median follow-up of 61.1 months. Of 21 TCC patients, 18 (85.7%) experienced
      disease recurrence (median time to recurrence, 5.3 months). Of the 5 CIS patients
      with complete response (CR), 3 (60%) experienced disease recurrence; (median time
      to recurrence, 37.3 months). Recurrence-free rates at 12 and 24 months were 20%
      (90% CI, 7.8%, 36.1%) and 15% (90 CI, 4.9%, 30.2%), respectively, for patients
      with TCC and 80% (90% CI, 31.4%, 95.8%) at both intervals for CIS patients with
      CR. Infection was the most common treatment-related toxicity; no grade 4 or
      higher toxicity was observed. The most common GU-specific toxicity was increased
      frequency/urgency. CONCLUSIONS: AD32 is safe and active for treatment of
      recurrent or refractory superficial bladder carcinoma. The agent awaits more
      complete characterization when drug production problems can be solved.

PMID- 18639471
TI  - Tissue-selective RNA interference in prostate cancer cell using prostate specific
      membrane antigen promoter/enhancer.
AB  - OBJECTIVES: RNA interference (RNAi) has the potential to be developed into
      therapeutics for prostate cancer, but the lack of cellular targets limits its
      application. In the present study we attempt to develop a prostate cancer
      specific RNAi system using the human prostate specific membrane antigen (PSMA)
      promoter/enhancer; furthermore, we analyzed its inhibitive effect on STAT3
      expression. METHODS: The adenoviral vectors containing a small hairpin RNA
      (shRNA) to target exogenous reporters enhance green fluorescent protein (EGFP)
      and endogenous gene signal transducers and activators of transcription 3 (STAT3)
      were constructed. After prostate cancer and other cells were transfected, reverse
      transcription-polymerase chain reaction (RT-PCR), fluorescence microscopy, and
      Western blotting were used to measure EGFP expression. Inhibition of STAT3 was
      evaluated by Western blotting. Cell proliferation and viability were measured by
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)
      assay. Cell apoptosis was analyzed with double-staining of Annexin V and PI.
      RESULTS: Our study showed that with the PSMA promoter/enhancer directly driving
      shRNA transcription, expression of the exogenous reporters EGFP in prostate
      cancer cells, but not other cancer cells and normal cells, was specifically
      inhibited in vitro. The PSMA promoter/enhancer-driven shRNA also depressed the
      expression of STAT3 in only prostate cancer cells. Inhibition of STAT3 suppressed
      proliferation of PC-3 and LNCaP cells. CONCLUSIONS: The present study describes
      an efficient RNAi system for gene silencing that is specific to prostate cancer
      cells using the PSMA promoter/enhancer. Suppression of STAT3 by using this system
      decreased proliferation and induced apoptosis of PC-3 and LNCaP cells. This
      system may be useful for RNAi therapy for prostate cancer.

PMID- 18639469
TI  - Inter-subject variability in the use of two different neuronal networks for
      reading aloud familiar words.
AB  - Cognitive models of reading predict that high frequency regular words can be read
      in more than one way. We investigated this hypothesis using functional MRI and
      covariance analysis in 43 healthy skilled readers. Our results dissociated two
      sets of regions that were differentially engaged across subjects who were reading
      the same familiar words. Some subjects showed more activation in left inferior
      frontal and anterior occipito-temporal regions while other subjects showed more
      activation in right inferior parietal and left posterior occipito-temporal
      regions. To explore the behavioural correlates of these systems, we measured the
      difference between reading speed for irregularly spelled words relative to
      pseudowords outside the scanner in fifteen of our subjects and correlated this
      measure with fMRI activation for reading familiar words. The faster the lexical
      reading the greater the activation in left posterior occipito-temporal and right
      inferior parietal regions. Conversely, the slower the lexical reading the greater
      the activation in left anterior occipito-temporal and left ventral inferior
      frontal regions. Thus, the double dissociation in irregular and pseudoword
      reading behaviour predicted the double dissociation in neuronal activation for
      reading familiar words. We discuss the implications of these results which may be
      important for understanding how reading is learnt in childhood or re-learnt
      following brain damage in adulthood.

PMID- 18639472
TI  - Relook TURBT in superficial bladder cancer: its importance and its correlation
      with the tumor ploidy.
AB  - OBJECTIVE: To evaluate various prognostic factor predictors of residual growth in
      Relook transurethral resection of bladder tumor (TURBT) in superficial bladder
      cancer. Also, to evaluate the role of Relook TURBT along with the ploidy for
      prediction of recurrence and stage progression in these patients. MATERIAL AND
      METHODS: Fifty patients with superficial bladder cancer underwent TURBT after
      complete evaluation. Ploidy of the tumor specimen was evaluated by flow
      cytometry. After 4 to 6 weeks of initial TURBT, these patients underwent Relook
      TURBT. Final treatment was given after the results of the histological evaluation
      of these specimens. Patients who underwent bladder sparing treatment were
      followed-up. RESULTS: Of the patients, 28.5% had residual tumor in Relook TURBT.
      Growth was found to be at the same site in 66.7% and at a different site 33.3%;
      75% had single while 25% had multiple residual growth. Residual malignant tissue
      had a statistically significant correlation with size of the tumor (>3 cm),
      appearance (solid tumor), number (>3), grade (high), and multiple previous
      resections. Overall, the up-migration of stage and grade leads to change in
      treatment in 41.6%; 5 underwent radical cystectomy and 1 opted for radiotherapy;
      in 2 patients, intravesical BCG was given. In follow-up of mean 11.5 months,
      16.6% had recurrence. Presence of residual growth in Relook TURBT along with
      number, size, morphology, and multiple previous resections were found to have
      significant correlation with the recurrence in these patients. Ploidy and grade
      of the tumor were not found to have correlation. CONCLUSIONS: Multiple, more than
      3 cm, solid high grade tumor with > 3 previous resections were predictors of
      presence of residual tumor in Relook TURBT. Presence of residual growth is a
      significant risk factor for recurrence. Ploidy was not found to be significantly
      correlated with recurrence.

PMID- 18639473
TI  - Isoforms of hyaluronidases can be a predictor of a prostate cancer of good
      prognosis.
AB  - INTRODUCTION: Hyaluronidases (HAases) are enzymes related to cancer progression.
      Isoforms of HAases have been described as products of alternative splicing
      responsible for differences in enzyme activity. The heterogeneity of HAase
      expression has been identified in tumors and could be related to the differences
      in their biological behavior. METHODS: Thirty-seven patients subjected to radical
      prostatectomy for prostate cancer were divided into 2 groups for the analyses:
      Low (< or =6-18) and high (> or =7-19) Gleason score and tumor behavior;
      recurrence 15 and nonrecurrence 22, mean follow-up 52.6 months. CONCLUSION: A
      profile of HAase related to low Gleason score and non-tumor recurrence was
      characterized by expression of HYAL3-v1, HYAL1-v3, and HYAL3-v2. More studies
      should be made in order to confirm with larger series.

PMID- 18639474
TI  - Minimum training requirement in ultrasound imaging of peripheral arterial
      disease.
AB  - OBJECTIVES: To demonstrate the minimum training requirement when performing
      ultrasound of peripheral arterial disease. DESIGN: Prospective and blinded
      comparative study. MATERIAL: 100 limbs in 100 consecutive patients suffering from
      peripheral arterial disease, 74% suffering critical limb ischemia, were enrolled
      during a 9 months period. METHODS: One physician with limited ultrasound
      experience performed all the ultrasound examinations of the arteries of the most
      symptomatic limb. Before enrolling any patients 15 duplex ultrasound examinations
      were performed supervised by an experienced vascular technologist. All patients
      had a digital subtraction arteriography performed by an experienced vascular
      radiologist, unaware of the ultrasound result. RESULTS: The number of
      insufficiently insonated segments (non-diagnostic segments) was significantly
      reduced during the study; from 9% among the initial 50 limbs to 2% among the last
      50 limbs (P<0.0001). This improvement was evident only in the infragenicular
      segments, as the performance within the supragenicular segments was good from the
      beginning. There was no change in the agreement between ultrasound and
      arteriography from the initial 50 patients (overall Kappa=0.66, (95%-CI: 0.60
      0.72); supragenicular Kappa=0.73 (95%-CI: 0.64-0.82); infragenicular Kappa=0.61
      (95%-CI: 0.54-0.69)) to the last 50 patients (overall Kappa=0.66 (95%-CI: 0.60
      0.72), supragenicular Kappa=0.67 (95%-CI: 0.57-0.76); infragenicular Kappa=0.66
      (95%-CI: 0.58-0.73)). CONCLUSION: The minimum training requirement in ultrasound
      imaging of peripheral arterial disease appears to be less than 50 ultrasound
      examinations (probably only 15 examinations) for the supragenicular segments and
      100 examinations for the infragenicular segments.

PMID- 18639475
TI  - Carotid endarterectomy: technical practices of surgeons participating in the GALA
      trial.
AB  - OBJECTIVE: Recent meta-analyses confirm an advantage to patch angioplasty during
      carotid endarterectomy (CEA) and suggest a benefit from routine shunting. GALA
      Trial (RCT: general [GA] versus local [LA] anaesthesia for CEA) collaborators
      (non-UK [European] and UK) were surveyed to assess current practice techniques.
      MATERIALS AND METHODS: Postal questionnaires determined: shunt usage, monitoring
      techniques dictating shunt deployment, criteria for patching and the influence of
      anaesthetic technique upon these decisions. RESULTS: 157/216 surgeons (73%)
      replied. For UK surgeons (n=76) performing GA CEA a shunt was always, never, or
      selectively used by 73.6%, 4.2% and 22.2% respectively. Figures for non-UK
      surgeons (n=77) were 20.8% (p<0.0001), 26% (p<0.0002) and 53.2% (p<0.0001). When
      shunting selectively, fewer UK surgeons relied on stump pressure (26.4% v 48.1%;
      p<0.0064) with TCD more widely used (38.9% v 11.7%; p<0.0001). Shunting criteria
      during LA CEA were the same for both groups (impaired awake-testing). Routine
      patching was commoner amongst UK surgeons (GA: 76.4% v 34.2%, p<0.0001; LA: 70.1%
      v 31.9%, p<0.0001). CONCLUSIONS: These results indicate that more UK surgeons
      have adopted current suggestions for improving CEA outcomes. Future analysis of
      unblinded GALA Trial data may provide further information about the impact of
      different policies for shunting and patching.

PMID- 18639476
TI  - Potential circulating biomarkers for abdominal aortic aneurysm expansion and
      rupture--a systematic review.
AB  - BACKGROUND: The maximal diameter of abdominal aortic aneurysms (AAAs) is the
      dominating indication for repair. However half of the AAAs repaired would never
      have ruptured if left unrepaired, although small AAAs occasionally rupture.
      Earlier surgery may be associated with a lower mortality. More precise indicators
      for surgery are warranted. This systematic review identifies potential systemic
      biomarkers for AAA rupture or expansion. METHODS: MEDLINE/PubMed and EMBASE (from
      1985 trough May 2007) were searched with the medical subject heading abdominal
      aortic aneurysm and keywords "size", "progression" or "growth" or "expansion
      rate" or "rupture" on the basis of MESH tree and as a text search restricted to
      English, German, French and Italian. In addition, reference lists were studied
      and manual searches performed. Observational studies investigating the
      association of circulating biomarkers with AAA rupture, expansion or size were
      selected. DATA EXTRACTION: Two reviewers (SU and GU) independently extracted the
      following data: year of publication, study characteristics, duration of follow
      up, circulating biomarker, AAA expansion rate or size or rupture. RESULTS: 699
      papers were identified. After exclusion of thoracic aneurysms and cardiac studies
      (n=118), surgical or medical treatment studies (n=179), case reports and animal
      studies (n=87), as well as reviews or letters (n=66), 249 articles were selected.
      Also excluded were 230 papers that did not report AAA size, expansion rate or
      rupture. 39 papers were included. Several potential biomarkers were identified.
      The strongest association with AAA was obtained with serum elastin peptides (SEP)
      and plasmin-antiplasmin (PAP) complexes. Matrix-degrading metalloproteinase 9
      (MMP9) and interferon-gamma (IFN-gamma) could have clinical potential while many
      putative biomarkers showed poor association. CONCLUSIONS: Several circulating
      agents in peripheral blood may predict AAA size, expansion rate or rupture. Few
      of them have clinical potential for future use. Confirmative studies and
      development of multivariate models are needed, together with continuing search
      for new biomarkers using the discovery based sciences within proteomics and/or
      genomics.

PMID- 18639477
TI  - Bone mineral density alterations in upper and lower extremities 12 months after
      stroke measured by peripheral quantitative computed tomography and DXA.
AB  - To evaluate the loss of trabecular and cortical bone mineral density (BMD) and
      geometric parameters of bone strength expressed by stress-strain index (SSI) in
      the proximal and distal forearm and the alterations of BMD in the hip of
      hemiplegic patient and 12 mo after stroke. Sixty-seven hemiplegic patients (43
      men and 24 women) with a history of single completed strokes associated with
      unilateral weakness were enrolled in this prospective study. All patients
      underwent bone densitometry measurements at 3, 6, and 12 mo after the initial
      episode of stroke. Both paretic and normal forearms were examined by peripheral
      quantitative computed tomography (pQCT) at the 4% and 20% sites of the forearm
      length and both hips were examined by dual-energy X-ray absorptiometry (DXA)
      including the area of femoral neck and greater trochanter. The diagnosis of
      stroke was confirmed by cranial computed tomography. Motor function was assessed
      by the functional ambulation category (FAC) and spasticity by the modified
      Ashworth scale (MAS). We found statistically significant trabecular and cortical
      bone density reductions during the course of our study in the forearm, which was
      more profound on the paretic side. Trabecular bone loss and SSI measured at 4% of
      the paretic forearm in the male group represented a 12-mo decrease of 14.01% and
      28.61%, respectively, and in the female group 9.29% and 19.17%, respectively.
      Cortical bone and SSI measured at the 20% site of paretic forearm in the male
      group corresponded to a 12-mo decrease of 4.02% and 7.43%, respectively, and in
      the female group 2.59% and 6.97%, respectively. Paretic femoral neck and
      trochanter measurements in males showed a reduction of 11.76% and 10.38%,
      respectively, and in females 13.04% and 12.6%, respectively. A significant loss
      of BMD and bone strength was found during the first year after stroke in both
      trabecular and cortical bone at the forearm and at the neck and great trochanter
      on the paretic hip. Most prominent BMD reduction was evident in men compared with
      perimenopausal women in the same age.

PMID- 18639479
TI  - [Irradiation of hepatocellular carcinoma: impact of breathing on motions and
      variations of volume of the tumor, liver and upper abdominal organs].
AB  - PURPOSE: To evaluate the amplitude of motion and the variations of volume of the
      tumor, the liver and upper abdominal organs induced by breathing during the
      irradiation of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Two scanners
      were performed in inhale and in exhale not forced in 20 patients with a HCC. The
      liver (left/right lobes), the tumor, the duodenum, the two kidneys and the
      pancreas were delineated on each acquisition. The superposition of the two
      spirals made it possible to measure the displacements and variations of volume of
      these structures in the craniocaudal (CC), lateral (Lat), and anteroposterior
      (AP) directions. RESULTS: The mean displacement of the tumour in CC, Lat and AP
      was of 19.7+/-8.3 mm, 4.5+/-2.3 mm, and 8.9+/-6.5 mm. The greatest amplitude of
      movement was obtained in CC for the right and left hepatic lobes (19+/-6.5 mm,
      10+/-5.6 mm), the duodenum(12.6+/-6.4 mm), the kidneys right and left (15.5+/-6.1
      mm, 16.2+/-10 mm) and the pancreas (13.2+/-6 mm). No significant variation of
      volume was observed for these organs. CONCLUSION: The movements of the tumour,
      the liver and the abdominal organs, induced by breathing are significant. The
      respiratory gating appears essential in particular with the development of new
      techniques of irradiation such as the intensity-modulated radiotherapy (IMRT) or
      the stereotactic body radiation therapy (SBRT).

PMID- 18639478
TI  - Determination of serum fPLI concentrations in cats with diabetes mellitus.
AB  - Diabetes mellitus (DM) is one of the most common feline endocrinopathies.
      Pancreatitis is a reported cause for poor control of DM in cats; however, its
      prevalence in diabetic cats is unknown. Measurement of serum feline pancreatic
      lipase immunoreactivity (fPLI) has been proposed as a sensitive and specific test
      for the detection of pancreatitis in cats. The aim of this study was to assess
      fPLI concentrations in diabetic cats and compare these with non-diabetic cats of
      similar age. Samples from 29 cats with DM and 23 non-diabetic cats were analysed.
      Serum fPLI concentrations were significantly higher in samples from diabetic cats
      (P<0.01). A weak association was found between serum fructosamine and fPLI
      concentrations (R(2)=0.355, P=0.015), but there was no association between fPLI
      concentrations and the degree of diabetic control. There were no significant
      differences in reported clinical signs between cats with or without DM regardless
      of serum fPLI concentration. This is the first study to demonstrate elevated
      serum fPLI concentrations in cats with DM, suggesting that pancreatitis could be
      a significant comorbidity in these cats.

PMID- 18639480
TI  - [Hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal
      carcinomatosis arising from gastric cancer].
AB  - Since 20 years, treatment of peritoneal carcinomatosis has been developed in
      expert centers. Cytoreductive surgery and perioperative intraperitoneal
      chemotherapy, especially hyperthermic intraperitoneal chemotherapy, was assessed
      by many nonrandomised studies for the treatment of peritoneal carcinomatosis
      arising from gastric cancer. Results described increased survival, especially for
      the most favourable cases: limited carcinomatosis and complete cytoreductive
      surgery. A strict selection of the patients is necessary because of the important
      morbidity of those treatments. Only patients with good general health, able to
      tolerate a threatening treatment, with possible complete cytoreduction, may
      benefit from those treatments. Many japanese studies had demonstrated the
      efficacy of hyperthermic intraperitoneal chemotherapy for the prophylactic
      treatment of carcinomatosis in advanced-gastric cancers. These results have to be
      confirmed by european randomised studies.

PMID- 18639481
TI  - Sequential anisotropic multichannel Wiener filtering with Rician bias correction
      applied to 3D regularization of DWI data.
AB  - It has been shown that the tensor calculation is very sensitive to the presence
      of noise in the acquired images, yielding to very low quality Diffusion Tensor
      Images (DTI) data. Recent investigations have shown that the noise present in the
      Diffusion Weighted Images (DWI) causes bias effects on the DTI data which cannot
      be corrected if the noise characteristic is not taken into account. One possible
      solution is to increase the minimum number of acquired measurements (which is 7)
      to several tens (or even several hundreds). This has the disadvantage of
      increasing the acquisition time by one (or two) orders of magnitude, making the
      process inconvenient for a clinical setting. We here proposed a turn-around
      procedure for which the number of acquisitions is maintained but, the DWI data
      are filtered prior to determining the DTI. We show a significant reduction on the
      DTI bias by means of a simple and fast procedure which is based on linear
      filtering; well-known drawbacks of such filters are circumvented by means of
      anisotropic neighborhoods and sequential application of the filter itself.
      Information of the first order probability density function of the raw data,
      namely, the Rice distribution, is also included. Results are shown both for
      synthetic and real datasets. Some error measurements are determined in the
      synthetic experiments, showing how the proposed scheme is able to reduce them. It
      is worth noting a 50% increase in the linear component for real DTI data, meaning
      that the bias in the DTI is considerably reduced. A novel fiber smoothness
      measure is defined to evaluate the resulting tractography for real DWI data. Our
      findings show that after filtering, fibers are considerably smoother on the
      average. Execution times are very low as compared to other reported approaches
      which allows for a real-time implementation.

PMID- 18639482
TI  - Retrograde signaling and plant stress: plastid signals initiate cellular stress
      responses.
AB  - Retrograde signaling coordinates the expression of nuclear genes encoding
      organellar proteins with the metabolic and developmental state of the organelle.
      These plastid signals are essential not only for coordinating photosynthetic gene
      expression in both the nucleus and in the chloroplasts but also for mediating
      plant stress responses. The chloroplasts therefore act as sensors of
      environmental changes and complex networks of plastid signals coordinate cellular
      activities and assist the cell during plant stress responses. Recent work
      suggests that information from both cytosolic-signaling and plastid-signaling
      networks must be integrated for the plant cell to respond optimally to
      environmental stress.

PMID- 18639483
TI  - Virulence mechanisms of Gram-positive plant pathogenic bacteria.
AB  - Actinobacteria and Firmicutes comprise a group of highly divergent prokaryotes
      known as Gram-positive bacteria, which are ancestral to Gram-negative bacteria.
      Comparative genomics is revealing that, though plant virulence genes are
      frequently located on plasmids or in laterally acquired gene clusters, they are
      rarely shared with Gram-negative bacterial plant pathogens and among Gram
      positive genera. Gram-positive bacterial pathogens utilize a variety of virulence
      strategies to invade their plant hosts, including the production of phytotoxins
      to allow intracellular and intercellular replication, production of cytokinins to
      generate gall tissues for invasion, secretion of proteins to induce cankers and
      the utilization and manipulation of sap-feeding insects for introduction into the
      phloem sieve cells. Functional analysis of novel virulence genes utilized by
      Actinobacteria and Firmicutes is revealing how these ancient prokaryotes
      manipulate plant, and sometimes insect, metabolic processes for their own
      benefit.

PMID- 18639484
TI  - Evaluation of magnolia bark extract in chromosomal aberration assays.
AB  - Magnolia bark extract (MBE) has been used historically in traditional Chinese and
      Japanese medicines, and more recently as a component of dietary supplements and
      cosmetic products. The genotoxic potential of MBE was studied in two in vitro
      chromosomal aberration assays. In Chinese hamster ovary (CHO) cells, exposure for
      3 h to MBE at concentrations of 0-30 microg/ml in the absence of a metabolic
      activation system (S9) and 0-7 microg/ml with S9 did not induce chromosomal
      aberrations, whereas higher concentrations were cytotoxic and did not allow for
      analysis of aberrations. Extended exposure for 18 h without metabolic activation
      at concentrations up to 15 microg/ml also resulted in a negative response. In V79
      cells derived from Chinese hamster lung tissue, treatment for 6h with
      concentrations up to 52 and 59 microg/ml in the absence and presence of S9,
      respectively, did not increase the incidence of chromosomal aberrations compared
      to negative controls. Furthermore, MBE exposure for 24 h without metabolic
      activation did not induce aberrations. The results of these studies demonstrate
      that MBE is not genotoxic under the conditions of the in vitro chromosomal
      aberration assays in CHO and V79 cells, and support the safety of MBE.

PMID- 18639485
TI  - Computer-based execution of clinical guidelines: a review.
AB  - PURPOSE: Clinical guidelines are useful tools to standardize and improve health
      care. The automation of the guideline execution process is a basic step towards
      its widespread use in medical centres. This paper presents an analysis and a
      comparison of eight systems that allow the enactment of clinical guidelines in a
      (semi) automatic fashion. METHODS: This paper presents a review of the literature
      (2000-2007) collected from medical databases as well as international conferences
      in the medical informatics area. RESULTS: Eight systems containing a guideline
      execution engine were selected. The language used to represent the guidelines as
      well as the architecture of these systems were compared. Different aspects have
      been assessed for each system, such as the integration with external elements or
      the coordination mechanisms used in the execution of clinical guidelines.
      Security and terminology issues complement the above study. CONCLUSIONS: Although
      these systems could be beneficial for clinicians and patients, it is an ongoing
      research area, and they are not yet fully implemented and integrated into
      existing careflow management systems and hence used in daily practice in health
      care institutions.

PMID- 18639486
TI  - Collaborative development of clinical templates as a national resource.
AB  - There is growing interest in the development of standards which structure
      information round discrete clinical concepts, in a way that supports system
      development and interoperability. Most notable are the openEHR Archetypes and
      Templates, and HL7 Templates. A project is described which explored the potential
      for these to engage and support clinical practitioners in developing clinical
      information standards in an open and accessible way. The project defined a
      clinical template as a clinical information model, which could be used to define
      the content of a form in a health record system, for example a continence
      assessment. The project followed three phases: professional development,
      including networking for content development; library implementation, including
      modelling and processes for managing content and relating to information
      standards; and implementation in working systems in a manner that is
      professionally acceptable. The project findings are encouraging although there
      remain some important issues to be explored in further work. The topic has now
      emerged as an important area of standards development, and a useful focus for
      international cooperation.

PMID- 18639487
TI  - Clinical information displays to improve ICU outcomes.
AB  - PURPOSE: In a previous study, we compared a prototype ecological display (ED)
      that represented physiological data in a structured pictorial format with two bar
      graph displays [J.A. Effken, Improving clinical decision making through
      ecological interfaces, Ecol. Psych. 18 (2006) 283-318]. In ED and the first bar
      graph display, data were grouped hierarchically based on a cognitive work
      analysis (CWA); in the second bar graph display they were grouped as usually
      collected. Treatment efficiency (i.e., percentage of time seven variables in the
      CWA model were in target range) improved similarly with the two displays
      incorporating the CWA order for intensive care unit (ICU) residents, but not for
      novice ICU nurses. Hypothesized reasons for this result included: insufficient
      practice with novel displays; use of identical histories across displays;
      insufficient clinical knowledge; and the variables used in the efficiency
      analysis, which included only one of ED's four integrated design elements. In the
      current study we tested these hypotheses. METHODS: We asked ICU nurses assigned
      to three knowledge groups based on intensive care and hemodynamic monitoring
      pretests to identify and treat oxygenation problems presented via ED and the
      first bar graph display (BGD) in an experimental laboratory simulation. We
      measured the impact of display, clinical scenario, data level, knowledge,
      presentation order, and practice extent on event recognition, treatment
      efficiency, cognitive workload, and user satisfaction. RESULTS: The two displays
      produced little difference in recognition speed or overall cognitive workload,
      but user satisfaction was greater with ED. When 12 variables were included in the
      analysis, treatment efficiency improved with ED; when only 7 were measured, BGD
      prevailed. The results suggest benefits for the kind of synthesis provided in ED,
      but also a potential limitation. If too many different pictorial formats are used
      in a display, detecting critical events may be more difficult.

PMID- 18639488
TI  - Real-time PCR compared to Binax NOW and cytospin-immunofluorescence for detection
      of influenza in hospitalized patients.
AB  - BACKGROUND: Rapid tests have had a significant impact on influenza diagnosis, but
      more accurate tests are needed for hospitalized patients who test negative by
      rapid methods. OBJECTIVE: We sought to determine the increased yield obtained
      from influenza RT-PCR in hospitalized patients compared to two rapid methods.
      STUDY DESIGN: Binax NOW, cytospin-enhanced direct immunofluoroescence (DFA), and
      influenza A and B multiplex TaqMan RT-PCR were performed on 237 clinical samples.
      RESULTS: Binax NOW detected 70 (53.0%), cytospin-DFA detected 127 (96.2%), and
      TaqMan RT-PCR detected 132 (100%) influenza-positive samples. The difference in
      sensitivity was significant between RT-PCR and Binax NOW (p<0.0001), but not
      between RT-PCR and cytospin-DFA (p=0.0736). Two samples testing positive for
      influenza B by all three methods, tested falsely positive for influenza A by
      Binax. Eight true positive samples did not become reactive by Binax until 30 min,
      and thus were counted as negative. CONCLUSIONS: The accuracy of real-time RT-PCR
      should greatly improve the diagnosis of influenza in hospitals using simple rapid
      flu tests, but may have a more modest impact in hospitals with expertise in
      cytospin-DFA. Further studies are needed to determine the effect of influenza RT
      PCR on patient management and costs in hospitalized patients.

PMID- 18639489
TI  - Co-circulations of two genotypes of dengue virus in 2006 out-break of dengue
      hemorrhagic fever in Karachi, Pakistan.
AB  - BACKGROUND: The status of dengue genotypes involved in the recent epidemic out
      breaks in Pakistan is not well defined. OBJECTIVES: We sought to analyze the
      predominant genotype responsible for the most severe and largest out-break of
      dengue hemorrhagic fever (DHF) that hit Karachi in 2006. STUDY DESIGN:
      Retrospective analysis of stored serum samples for dengue virus genotype by
      multiplex RT-PCR, anti-dengue IgM, IgG and review of clinical charts of patients
      admitted to Aga Khan University Hospital. RESULTS: Viral RNA detection of 250
      patients revealed positive results in 185 (74.0%) samples. DEN-2 was predominant
      genotype (n=104, 56.2%) Dengue specific antibodies were detected in 139 samples
      of which 81 were classified as primary cases. DEN-2 accounted for these. Within
      secondary cases, 63.2% were due to DEN-2 (total 57), the rest were positive for
      DEN-3. DHF (p=0.064) and abdominal pain (p=0.059) were more frequently associated
      with DEN-2 as compared to DEN-3. None of the samples were positive for DEN-1 or
      DEN-4. CONCLUSION: Co-circulation of DEN-2 and DEN-3 was responsible for the 2006
      out-break in Karachi. Primary and secondary cases were seen in both groups. Cases
      with DHF showed marginal association with DEN-2. Introduction of a new serotype
      (DEN-3) and or a genotypic shift of endemic serotype (DEN-2) are the probable
      factors for the recent out-break of DHF in this region.

PMID- 18639490
TI  - Ocular vestibular evoked myogenic potentials to bone conducted vibration of the
      midline forehead at Fz in healthy subjects.
AB  - OBJECTIVE: To provide the empirical basis for using ocular vestibular evoked
      myogenic potentials (oVEMPS) in response to Fz bone conducted vibration (BCV)
      stimulation to indicate vestibular function in human subjects. To show the
      generality of the response by testing a large number of unselected healthy
      subjects across a wide age range and the repeatability of the response within
      subjects. To provide evidence that the response depends on otolithic function.
      METHODS: The early negative component (n10) of the oVEMP to brief BCV of the
      forehead, in the midline at the hairline (Fz) is recorded by surface EMG
      electrodes just beneath the eyes. We used a Bruel and Kjaer 4810 Mini-Shaker or a
      light tap with a tendon hammer to provide adequate BCV stimuli to test a large
      number (67) of unselected healthy people to quantify the individual differences
      in n10 magnitude, latency and symmetry to Fz BCV. A Radioear B-71 bone oscillator
      at Fz is not adequate to elicit a reliable n10 response. RESULTS: The n10 oVEMP
      response showed substantial differences in amplitude between subjects, but is
      repeatable within subjects. n10 is of equal magnitude in both eyes with an
      average asymmetry around 11%. The average n10 amplitude for Mini Tone Burst BCV
      is 8.47microV+/-4.02 (sd), the average latency is 10.35ms+/-0.63 (sd). The
      amplitude of n10 decreases and its latency increases with age. CONCLUSIONS:
      oVEMPs are a new reliable, repeatable test to indicate vestibular and probably
      otolithic function. SIGNIFICANCE: This study shows the optimum conditions for
      recording oVEMPs and provides baseline values for individual differences and
      asymmetry. oVEMPs can be measured in senior subjects without difficulty.

PMID- 18639491
TI  - Cancer survival in five continents: a worldwide population-based study (CONCORD).
AB  - BACKGROUND: Cancer survival varies widely between countries. The CONCORD study
      provides survival estimates for 1.9 million adults (aged 15-99 years) diagnosed
      with a first, primary, invasive cancer of the breast (women), colon, rectum, or
      prostate during 1990-94 and followed up to 1999, by use of individual tumour
      records from 101 population-based cancer registries in 31 countries on five
      continents. This is, to our knowledge, the first worldwide analysis of cancer
      survival, with standard quality-control procedures and identical analytic methods
      for all datasets. METHODS: To compensate for wide international differences in
      general population (background) mortality by age, sex, country, region, calendar
      period, and (in the USA) ethnic origin, we estimated relative survival, the ratio
      of survival noted in the patients with cancer, and the survival that would have
      been expected had they been subject only to the background mortality rates. 2800
      life tables were constructed. Survival estimates were also adjusted for
      differences in the age structure of populations of patients with cancer.
      FINDINGS: Global variation in cancer survival was very wide. 5-year relative
      survival for breast, colorectal, and prostate cancer was generally higher in
      North America, Australia, Japan, and northern, western, and southern Europe, and
      lower in Algeria, Brazil, and eastern Europe. CONCORD has provided the first
      opportunity to estimate cancer survival in 11 states in USA covered by the
      National Program of Cancer Registries (NPCR), and the study covers 42% of the US
      population, four-fold more than previously available. Cancer survival in black
      men and women was systematically and substantially lower than in white men and
      women in all 16 states and six metropolitan areas included. Relative survival for
      all ethnicities combined was 2-4% lower in states covered by NPCR than in areas
      covered by the Surveillance Epidemiology and End Results (SEER) Program. Age
      standardised relative survival by use of the appropriate race-specific and state
      specific life tables was up to 2% lower for breast cancer and up to 5% lower for
      prostate cancer than with the census-derived national life tables used by the
      SEER Program. These differences in population coverage and analytical method have
      both contributed to the survival deficit noted between Europe and the USA, from
      which only SEER data have been available until now. INTERPRETATION: Until now,
      direct comparisons of cancer survival between high-income and low-income
      countries have not generally been available. The information provided here might
      therefore be a useful stimulus for change. The findings should eventually
      facilitate joint assessment of international trends in incidence, survival, and
      mortality as indicators of cancer control.

PMID- 18639492
TI  - Lack of alpha-1 integrin alters lesion morphology during pulmonary Mycobacterium
      tuberculosis infection.
AB  - The hallmark of Mycobacterium tuberculosis infection is the granuloma, a highly
      dynamic immune structure that contains the bacilli during chronic infection.
      Here, we examined if alpha1beta1 integrin is required in the development and
      maintenance of the granulomatous structure during pulmonary infection using the
      alpha1 integrin knockout (alpha1-null) mouse. The alpha1beta1 integrin is
      expressed on activated macrophages and T cells, and interacts with collagen
      molecules in the extracellular matrix (ECM), and thus may play a role in the
      granulomatous process. Following pulmonary infection with virulent M.
      tuberculosis, lungs of alpha1-null infected mice had striking differences in
      granuloma structure, as well as distinct and markedly thickened alveolar septae.
      By day 180, there were regions of cell death within granulomatous lesions,
      characterized by cellular debris in these mice. To determine if this molecule was
      necessary for T cell trafficking within the lungs, the expression of CD4, CD44
      and CD62L was monitored. The number of activated and IFN-gamma-producing CD4+ T
      cells increased in the lungs of alpha1-null mice during the chronic phase of
      infection, although they had decreased concentrations of TNF-alpha and MMP-9.
      These results suggest that while alpha1beta1 integrin is not required for
      trafficking or maintenance of T cells in M. tuberculosis infected lungs, it does
      play a role in granuloma structure and integrity during the chronic phase of
      infection.

PMID- 18639493
TI  - The activated stroma index is a novel and independent prognostic marker in
      pancreatic ductal adenocarcinoma.
AB  - BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly
      desmoplastic tumor with an innate resistance to therapy. Pancreatic stellate
      cells (PSCs) produce this excessively desmoplastic microenvironment. The impact
      of PSC activity on PDAC behavior in vivo is analyzed. METHODS: 233 patients who
      underwent surgery for PDAC were evaluated by immunohistochemistry using
      antibodies against alpha-smooth muscle actin as a marker of PSC activity. Aniline
      was used to stain collagen deposition. The ratio of alpha-smooth muscle actin
      stained area to collagen-stained area was defined as the activated stroma index
      (ASI). Survival analysis was performed using the Kaplan-Meier method. Prognostic
      factors were determined in a multivariable analysis using a Cox proportional
      hazards model. RESULTS: Four major patterns of collagen deposition were defined
      with regard to PSC activity. The combination of high stromal activity and low
      collagen deposition was associated with a worse prognosis, whereas the
      combination of high collagen deposition and low stromal activity indicated a
      better prognosis. Patients with the lowest ASI had the best median survival rate
      (25.7 mo). The highest ASI was found in patients with the worst median survival
      rate (16.1 mo; P = .007; lowest vs highest ASI: hazard ratio, 1.61; 95%
      confidence interval, 1.014-2.562). ASI was an independent prognostic marker in
      multivariable survival analysis comparable with the nodal status of cancer.
      CONCLUSIONS: The activated stroma index is a novel independent prognostic marker
      in PDAC in cases undergoing surgery. This finding highlights the impact of the
      microenvironment in cancer progression and on patient survival.

PMID- 18639494
TI  - Altered DNA mismatch repair expression in synchronous and metachronous colorectal
      cancers.
AB  - BACKGROUND & AIMS: It is not clear what proportion of synchronous or metachronous
      colorectal cancers (CRCs) are associated with DNA mismatch repair (MMR)
      alterations or unsuspected Lynch syndrome. On the basis of tissue analyses, the
      aims were to evaluate DNA MMR expression in metachronous, synchronous, and
      isolated sporadic CRCs and to assess within-patient concordance of MMR expression
      in metachronous and synchronous CRCs. METHODS: Tissue was evaluated from 34
      patients with metachronous CRC, 34 matched solitary CRC patients, and 40 patients
      with synchronous CRCs. Subjects with known hereditary CRC were excluded.
      Immunohistochemical staining for MLH1 and MSH2 was performed on all tissues.
      RESULTS: Absent MLH1 or MSH2 staining of the initial metachronous tumor was
      observed in 27% compared with 21% of control CRCs, P = .58. The odds of
      metachronicity with absent immunostaining were 1.33 (95% confidence interval,
      0.46-3.84). Loss of MMR expression was observed in at least one cancer in 30% of
      patients with synchronous CRC. MMR expression loss was discordant in 70% of
      metachronous CRCs and 50% of synchronous CRCs. Lynch syndrome was subsequently
      diagnosed in 2 patients with synchronous CRCs, both with concordant tumor MMR
      loss but in no patient with metachronous CRC. CONCLUSIONS: Among those without
      known Lynch syndrome, development of multiple primary CRCs appears to be due
      largely to somatic events and often occurs via different molecular pathways
      within the same patient. Altered MMR expression in sporadic CRC has low
      predictive value for metachronicity. MMR expression analysis in cases of multiple
      primary CRC might identify a small number of patients with unsuspected Lynch
      syndrome.

PMID- 18639495
TI  - Effect of a time-dependent colonoscopic withdrawal protocol on adenoma detection
      during screening colonoscopy.
AB  - BACKGROUND & AIMS: Screening colonoscopy can prevent cancer by removal of
      adenomatous polyps. Recent evidence suggests that insufficient time for
      inspection during overly rapid colonoscope withdrawal may compromise adenoma
      detection. We conducted a study of the effect of a minimum prespecified time for
      instrument withdrawal and careful inspection on adenoma detection rates during
      screening colonoscopy. METHODS: Baseline data consisted of neoplasia detection
      rates during 2053 screening colonoscopies performed without a specified
      withdrawal protocol. During a subsequent 13-month period we performed 2325
      screening colonoscopies using dedicated inspection techniques and a minimum 8
      minute withdrawal time. With colonoscopists comprising the study population, we
      compared overall and individual rates of neoplasia detection in postintervention
      procedures with those in baseline examinations. RESULTS: As compared with
      baseline subjects, postintervention subjects had higher rates of any neoplasia
      (34.7% vs 23.5%, P < .0001) and of advanced neoplastic lesions per patient
      screened (0.080 +/- 0.358 vs 0.055 +/- 0.241, P < .01). Twenty-five percent of
      advanced neoplastic lesions detected in postintervention examinations were 9 mm
      or less in diameter, versus 10% in baseline examinations (P < .001). Endoscopists
      with mean withdrawal times of 8 minutes or longer had higher rates of detection
      of any neoplasia (37.8% vs 23.3%, P < .0001) and of advanced neoplasia (6.6% vs
      4.5%, P = .13) compared with those with mean withdrawal times of less than 8
      minutes. CONCLUSIONS: After implementing a protocol of careful inspection during
      a minimum of 8 minutes to withdraw the colonoscope, we observed significantly
      greater rates of overall and advanced neoplasia detection during screening
      colonoscopy.

PMID- 18639496
TI  - Detection of cholangiocarcinoma in vivo using miniprobe-based confocal
      fluorescence microscopy.
AB  - BACKGROUND & AIMS: The preoperative diagnosis of cholangiocarcinoma is associated
      with a low sensitivity. To overcome this limitation, a new imaging modality was
      evaluated to detect neoplasia in vivo in the biliary tract. METHODS: Fourteen
      patients with biliary strictures were examined. Mucosal imaging was performed
      with a miniaturized confocal laser scanning miniprobe introduced via the
      accessory channel of a cholangioscope. Thereafter, targeted biopsy specimens were
      taken from the same regions. RESULTS: All strictures could be reached. Presence
      of irregular vessels use confocal laser microscopy enabled prediction of
      neoplasia with an accuracy rate of 86%, sensitivity of 83%, and specificity of
      88%. The respective numbers for standard histopathology were 79%, 50%, and 100%.
      The mean signal-to-noise-ratio of laser microscopic images acquired from
      malignant strictures differed significantly from those of benign origin (1.8 +/-
      0.8 vs 2.6 +/- 1.0; P = .005). CONCLUSIONS: Miniprobe-based confocal laser
      scanning microscopy considerably increases sensitivity for the detection of
      biliary neoplasia and therefore represents a promising diagnostic approach.

PMID- 18639497
TI  - Persistent Helicobacter pylori infection after a course of antimicrobial therapy
      what's next?

PMID- 18639498
TI  - Noncirrhotic portal hypertension in patients with human immunodeficiency virus-1
      infection.
AB  - BACKGROUND & AIMS: Noncirrhotic portal hypertension (NCPH) is unusual in North
      American patients. This study characterized patients with NCPH and human
      immunodeficiency virus-1 (HIV-1) infection to identify potential risk factors for
      this association. METHODS: Eleven consecutive patients from our urban hepatology
      clinic with HIV-1 infection and NCPH were the subject of this series. Case
      histories, including medication lists and laboratory data, were analyzed.
      RESULTS: Age at diagnosis was 51 +/- 7 years. CD4 count was 303 +/- 185 cells/mL,
      and HIV viral load was <75 copies/mL in 9 patients. Didanosine was the only
      medication taken by all patients; 10 each had taken lamivudine and zidovudine. In
      the 10 patients tested, 8 had at least 1 thrombophilic abnormality; 6 were
      deficient in protein S, and 2 had multiple abnormalities. Nodular regenerative
      hyperplasia was observed in all 11 and portal venulopathy in 5 patients. All
      patients had esophageal varices; 3 developed variceal bleeding. Six patients had
      ascites; 2 required transjugular intrahepatic portal systemic shunt. CONCLUSIONS:
      Exposure to didanosine and/or a hypercoagulable tendency might predispose
      patients infected with HIV-1 to vascular changes resulting in NCPH.

PMID- 18639499
TI  - Severe and refractory chronic abdominal pain: treatment strategies.

PMID- 18639500
TI  - Mutations at position 7445 in the precursor of mitochondrial tRNA(Ser(UCN)) gene
      in three maternal Chinese pedigrees with sensorineural hearing loss.
AB  - We report here the clinical, genetic and molecular characterization of three
      Chinese pedigrees with nonsyndromic bilateral hearing loss. Clinical and genetic
      evaluations revealed the variable severity and age-of-onset in hearing impairment
      in these families. Strikingly, there were extremely low penetrances of hearing
      impairment in these Chinese families. Sequence analysis of the complete
      mitochondrial DNA (mtDNA) showed the known A7445C mutation in two pedigrees and
      the novel A7445T mutation in another pedigree, in addition to distinct sets of
      mtDNA polymorphisms belong to Asian haplogroups D4j and F4. Indeed, the A7445C or
      A7445T mutation in the CO1 and the precursor of tRNA(Ser(UCN)) genes was present
      in homoplasmy only in the maternal lineage of those pedigrees but not other
      members of these families and 164 Chinese controls. In fact, the A7445C or A7445T
      mutation results in a read-through of the stop condon AGA of the CO1 message on
      the H strand of mtDNA, thereby adding three amino acids (Ser-Gln-Lys) to the C
      terminal of the polypeptide. However, the mutated polypeptide may retain a
      partial function. Alternatively, the A7445C or A7445T mutation is adjacent to the
      site of 3' end endonucleolytic processing of L-strand RNA precursor, spanning
      tRNA(Ser(UCN)) and ND6 mRNA. Thus, the A7445C or A7445T mutation may also cause a
      defect in the processing of the L-strand RNA precursor, thus causing
      mitochondrial dysfunctions. Furthermore, the occurrence of the mutations at
      position 7445 in these genetically unrelated subjects affected by hearing
      impairment strongly indicates that mutations at the position 7445 are involved in
      the pathogenesis of hearing impairment.

PMID- 18639501
TI  - Simplified method for determination of clarithromycin in human plasma using
      protein precipitation in a 96-well format and liquid chromatography-tandem mass
      spectrometry.
AB  - A simplified method to determine clarithromycin concentrations in human plasma
      using protein precipitation in a 96-well plate and liquid chromatography-tandem
      mass spectrometry was developed and validated. Plasma proteins were precipitated
      with acetonitrile and roxithromycin was used as the internal standard. After
      vortex mixing and centrifugation, the supernatants were directly injected onto a
      Phenomenex Luna Phenyl-Hexyl column (50 mm x 2.0 mm ID, 3 microm). The mobile
      phase consisted of water and methanol (30:70, v/v) containing 0.1% formic acid
      and 5mM ammonium acetate. The flow rate was 0.22 mL/min and the total run time
      (injection to injection) was less than 3 min. Detection of the analytes was
      achieved using positive ion electrospray tandem mass spectrometry in selected
      reaction monitoring (SRM) mode. The linear standard curve ranged from 100 to 5000
      ng/mL and the precision and accuracy (inter- and intra-run) were within 7.9% and
      4.9%, respectively. The method was successfully used to determine clarithromycin
      concentrations in human plasma samples obtained from healthy subjects who were
      given clarithromycin 500 mg for 3 days. The method is rapid, simple, precise and
      directly applicable to clarithromycin pharmacokinetic studies.

PMID- 18639502
TI  - Application of a sensitive liquid chromatographic/tandem mass spectrometric
      method to a pharmacokinetic study of allylestrenol in healthy Chinese female
      volunteers.
AB  - A sensitive, specific and rapid liquid chromatographic/tandem mass spectrometric
      (LC/MS/MS) assay for the determination of allylestrenol in human plasma was
      established. Plasma samples were extracted by tert-butyl ether and separated by
      LC/MS/MS using a Phenomenex Curosil-PFP column (250 mm x 4.6 mm ID, dp 5 microm)
      with a mobile phase of methanol-water (95:5, v/v). The analytes were monitored
      with atmospheric pressure chemical ionization (APCI) by selected reaction
      monitoring (SRM) mode. The linear calibration curves covered a concentration
      range of 0.04-20.0 ng/mL with lower limit of quantification (LLOQ) at 0.04 ng/mL.
      The mean extraction recovery of allylestrenol was greater than 81.8%. The intra-
      and inter-day precisions were less than 1.3% and 3.1% respectively, determined
      from quality control (QC) samples of three representative concentrations. The
      method has been successfully applied to determining the plasma concentration of
      allylestrenol and a clinical pharmacokinetics study in healthy Chinese female
      volunteers.

PMID- 18639503
TI  - Investigation on the spectrum-effect relationships of EtOAc extract from Radix
      Isatidis based on HPLC fingerprints and microcalorimetry.
AB  - This work investigated the spectrum-effect relationships between HPLC
      fingerprints and the anti-bacterial activities of EtOAc extracts from Radix
      Isatidis. Fingerprints of EtOAc extracts of Radix Isatidis from various sources
      were established by a High-Performance Liquid Chromatography. The process of
      Escherichia coli (E. coli) growth affected by EtOAc extracts was monitored using
      a Thermal Activity Monitor (TAM) Air Isothermal Calorimeter by microcalorimetry.
      By analyzing the power-time curves, quantitative parameters, such as growth rate
      constant k, maximum heat-production rate P(m), appearance time t and total heat
      production Q were obtained to characterize the interactions of E. coli and the
      EtOAc extracts from Radix Isatidis. The HPLC fingerprints were investigated using
      hierarchical clustering analysis. The main thermo-kinetic parameters from the
      power-time curves were analyzed using principal component analysis. The spectrum
      effect relationships between the HPLC fingerprints and anti-bacterial activities
      were analyzed with multivariant correlation analysis. Close correlation existed
      between the spectrum-effect relationships of the EtOAc extracts. Salicylic acid
      in the HPLC fingerprints might be one of the anti-bacterial components. This work
      provides a general model of the combination of HPLC and microcalorimetry to study
      the spectrum-effect relationships of EtOAc extracts from Radix Isatidis, which
      can be used to search for principal components of Radix Isatidis on bioactivity.

PMID- 18639504
TI  - Preparative chromatographic resolution of racemates using HPLC and SFC in a
      pharmaceutical discovery environment.
AB  - The preparative chromatographic resolution of racemates has become a standard
      approach for the generation of enantiomers in pharmaceutical discovery
      laboratories. This paper will discuss the use of preparative HPLC and SFC to
      generate individual enantiomers for discovery activities. Analytical HPLC and SFC
      method development to rapidly screen chiral stationary phases and solvent
      combinations will be presented. The usefulness of preparative chromatographic
      resolution of racemates will be demonstrated through the presentation of numerous
      non-routine case studies from the laboratories at Amgen.

PMID- 18639505
TI  - One-step rapid determination and purification of puerarin from Radix puerariae by
      n-octylamine-modified poly(methacrylate-co-ethylene dimethacrylate) monolith.
AB  - n-Octylamine-modified poly(methacrylate-co-ethylene dimethacrylate) monoliths
      were prepared for rapid screening, determination and one-step purification of
      puerarin from Radix puerariae (a crude extract of the root of Pueraria lobata).
      The modified monolith showed a specific surface area of 17.8 m(2) g(-1), an
      average pore size of 0.76 microm and a total porosity of 60.8%. Fast separation
      of R. puerariae crude extract was achieved within 5 min at a flow velocity of 722
      cm h(-1) resulting in a puerarin purity of 97%, with a recovery of 85%. This
      demonstrates the potential of n-octylamine-modified poly(methacrylate-co-ethylene
      dimethacrylate) monolith for the rapid analysis and separation of isoflavonoids.
      Preparative scale sample loading (12 mg in 2 mL) resulted in a purity of 95%, and
      a recovery of about 69%. HPLC, FTIR, MS and (1)H NMR spectroscopy were used for
      the characterization and quantification of puerarin in isolated fraction.

PMID- 18639506
TI  - Use of the anterolateral thigh flap and combined vascularised fascia lata sling
      to provide static support following facial nerve resection in head and neck
      cancer reconstruction.

PMID- 18639507
TI  - Minimising false positive margins in BCC excision: point of technique.

PMID- 18639508
TI  - A simple device for vacuum-assisted closure therapy in noncontiguous wounds.

PMID- 18639509
TI  - Nasal reconstruction in a patient with prolidase deficiency syndrome.

PMID- 18639510
TI  - Unilateral hypoplastic breast in a male-to-female transsexual with Poland
      syndrome after gender reassignment--reconstructive considerations.
AB  - Gender reassignment procedures are performed more frequently nowadays due to a
      multidisciplinary approach and improved techniques and selection process. Many
      male-to-female patients require bilateral breast augmentation as part of the
      transformation following the gender reassignment if they fail to develop female
      breast features after hormonal treatment. We report on a very rare incidence of
      male-to-female gender reassignment in a patient with Poland syndrome. A male-to
      female transsexual on hormonal therapy for gender reassignment developed one
      normal female-shaped breast whereas the other breast remained hypoplastic. As a
      male, he was not aware of his chest wall deformity but it became a major issue
      after successful gender reassignment surgery. Our experience with the specific
      reconstructive considerations and recommendations regarding our surgical approach
      to this complex reconstructive problem are discussed.

PMID- 18639511
TI  - Retrospective outcome analysis of temporalis muscle transfer for the treatment of
      paralytic lagophthalmos.
AB  - Temporalis muscle transfer for paralytic lagophthalmos, which was first proposed
      by Gillies and later developed by Andersen, has been one of the most common
      treatment modalities for paralytic lagophthalmos. However, there have been no
      scientific reports statistically analysing the efficacy of temporalis muscle
      transfer. We, therefore, retrospectively analysed the functional and aesthetic
      results of temporalis muscle transfer. Between 1994 and 2006, we carried out
      temporalis muscle transfer (the so-called Gillies-Andersen method) on 95
      established facial paralysis patients. We sent a postal questionnaire to these
      patients and 47 of them responded. The functional and aesthetic results were
      analysed based on the patients' replies together with clinical records and
      photographs, and unfavourable factors of this procedure were investigated. After
      surgery, most ocular symptoms (mechanical irritation, dry eye, soreness, and
      discharge) improved significantly. Achievement rate of complete eye closure was
      78.7%. A morphometric study revealed that possible unfavourable factors (old age,
      intracranial disease, use of dentures, etc.) did not affect the achievement rates
      of complete eye closure. Deformity of eyelid fissure due to undue tension of the
      temporal fascia fixation was found in nine patients (19.1%) and six of these
      patients underwent secondary revision. Unlike lid loading with a gold implant,
      the results of temporalis muscle transfer depend greatly on the surgeon's skill.
      However, if this procedure is performed properly, strong eye closure can be
      obtained. We, therefore, recommend temporalis muscle transfer as the preferred
      option for reconstruction of paralytic lagophthalmos.

PMID- 18639512
TI  - "Glue Ear": beginning of the end for head bandages after prominent ear
      correction?

PMID- 18639513
TI  - Changes in the aging upper lip--a photomorphometric and MRI-based study (on a
      quest to find the right rejuvenation approach).
AB  - BACKGROUND: A lack of scientific data about the complex three dimensional changes
      in relation to the rest of the face is the reason for the multitude of
      rejuvenation approaches to the aging upper lip. In this study the underlying
      anatomic changes and facial proportions of the senile upper lip are
      scientifically evaluated for the first time. METHODS: (1) In 182 standardized
      subject photographs proportions of the upper lip were measured, compared to
      facial dimensions and correlated to age. (2) In cranial MRI scans of 30 women
      aged 20-35 and 30 women aged 65-80 relevant anatomical dimensions were measured.
      RESULTS: Both studies showed a statistically significant lengthening of the aging
      upper lip. The photomorphometric study further shows an increase of prolabium
      skin at the cost of a decreasing visible upper lip vermilion. The MRI scans
      showed a decrease in thickness. A loss of volume could not be shown. CONCLUSION:
      Isolated volume augmentation is not a causal method of upper lip rejuvenation and
      it may therefore rather lead to an unnatural 'blown up' look.

PMID- 18639514
TI  - AutoDecon, a deconvolution algorithm for identification and characterization of
      luteinizing hormone secretory bursts: description and validation using synthetic
      data.
AB  - Hormone signaling is often pulsatile, and multiparameter deconvolution procedures
      have long been used to identify and characterize secretory events. However, the
      existing programs have serious limitations, including the subjective nature of
      initial peak selection, lack of statistical verification of presumed bursts, and
      user-unfriendliness of the application. Here we describe a novel deconvolution
      program, AutoDecon, which addresses these concerns. We validate AutoDecon for
      application to serum luteinizing hormone (LH) concentration time series using
      synthetic data mimicking real data from normal women and then comparing the
      performance of AutoDecon with the performance of the widely employed hormone
      pulsatility analysis program Cluster. The sensitivity of AutoDecon is higher than
      that of Cluster ( approximately 96% vs. 80%, P=0.001). However, Cluster had a
      lower false-positive detection rate than did AutoDecon (6% vs. 1%, P=0.001).
      Further analysis demonstrated that the pulsatility parameters recovered by
      AutoDecon were indistinguishable from those characterizing the synthetic data and
      that sampling at 5- or 10-min intervals was optimal for maximizing the
      sensitivity rates for LH. Accordingly, AutoDecon presents a viable nonsubjective
      alternative to previous pulse detection algorithms for the analysis of LH data.
      It is applicable to other pulsatile hormone concentration time series and many
      other pulsatile phenomena. The software is free and downloadable at
      http://mljohnson.pharm.virginia.edu/home.html.

PMID- 18639515
TI  - Direct electron transfer from graphite and functionalized gold electrodes to T1
      and T2/T3 copper centers of bilirubin oxidase.
AB  - Direct electron transfer (DET) from bare spectrographic graphite (SPGE) or 3
      mercaptopropionic acid-modified gold (MPA-gold) electrodes to Trachyderma
      tsunodae bilirubin oxidase (BOD) was studied under anaerobic and aerobic
      conditions by cyclic voltammetry and chronoamperometry. On cyclic voltammograms
      nonturnover Faradaic signals with midpoint potentials of about 700 mV and 400 mV
      were clearly observed corresponding to redox transformations of the T1 site and
      the T2/T3 cluster of the enzyme, respectively. The immobilized BOD was
      differently oriented on the two electrodes and its catalysis of O(2)
      electroreduction was also massively different. On SPGE, where most of the enzyme
      was oriented with the T1 copper site proximal to the carbon with a quite slow ET
      process, well-pronounced DET-bioelectroreduction of O(2) was observed, starting
      already at >700 mV vs. NHE. In contrast, on MPA-gold most of the enzyme was
      oriented with its T2/T3 copper cluster proximal to the metal. Indeed, there was
      little DET-based catalysis of O(2)-electroreduction, even though the ET between
      the MPA-gold and the T2/T3 copper cluster of BOD was similar to that observed for
      the T1 site at SPGE. When BOD actively catalyzes the O(2)-electroreduction, the
      redox potential of its T1 site is 690 mV vs. NHE and that of one of its T2/T3
      copper centers is 390 mV vs. NHE. The redox potential of the T2/T3 copper cluster
      of a resting form of BOD is suggested to be about 360 mV vs. NHE. These values,
      combined with the observed biocatalytic behavior, strongly suggest an uphill
      intra-molecular electron transfer from the T1 site to the T2/T3 cluster during
      the catalytic turnover of the enzyme.

PMID- 18639516
TI  - Abeta peptide interactions with isoflurane, propofol, thiopental and combined
      thiopental with halothane: a NMR study.
AB  - Abeta peptide is the major component of senile plaques (SP) which accumulates in
      AD (Alzheimer's disease) brain. Reports from different laboratories indicate that
      anesthetics interact with Abeta peptide and induce Abeta oligomerization. The
      molecular mechanism of Abeta peptide interactions with these anesthetics was not
      determined. We report molecular details for the interactions of uniformly (15)N
      labeled Abeta40 with different anesthetics using 2D nuclear magnetic resonance
      (NMR) experiments. At high concentrations both isoflurane and propofol perturb
      critical amino acid residues (G29, A30 and I31) of Abeta peptide located in the
      hinge region leading to Abeta oligomerization. In contrast, these three specific
      residues do not interact with thiopental and subsequently no Abeta
      oligomerization was observed. However, studies with combined anesthetics
      (thiopental and halothane), showed perturbation of these residues (G29, A30 and
      I31) and subsequently Abeta oligomerization was found. Perturbation of these
      specific Abeta residues (G29, A30 and I31) by different anesthetics could play an
      important role to induce Abeta oligomerization.

PMID- 18639517
TI  - Staphylococcus aureus giant protein Ebh is involved in tolerance to transient
      hyperosmotic pressure.
AB  - Staphylococcus aureus is well known to colonize on human skin where the
      physiological condition is characterized by hypervariable water activity, i.e.,
      repeated dehydration or rehydration. To determine the facilitating factors for
      the colonization under hypervariable water activity, we studied the giant protein
      Ebh (extracellular matrix (ECM)-binding protein homologue). The ebh mutant RAM8
      showed invaginated vacuoles along the septum, similar to that found in partial
      plasmolysis, and the cells burst under osmotic upshift. RAM8 was also relatively
      susceptible to abrupt hyperosmotic upshift, teicoplanin, and Triton X-100. By
      using the green fluorescent protein (GFP) as a reporter, Ebh was localized over
      the entire cell surface. This suggests that Ebh might contribute to structural
      homeostasis by forming a bridge between the cell-wall and cytoplasmic membrane to
      avoid plasmolysis under hyperosmotic condition.

PMID- 18639518
TI  - Interleukin-20 targets renal cells and is associated with chronic kidney disease.
AB  - Interleukin (IL)-10 is an anti-inflammatory factor that suppresses renal fibrosis
      and improves renal function in CKD rats. IL-20 belongs to the IL-10 family;
      therefore, we sought to determine whether IL-20 is involved in CKD. CKD patients
      at stage five expressed significantly higher IL-20 in serum than controls.
      Immunohistochemical staining demonstrated that more IL-20 protein was expressed
      in the kidney tubular-epithelial cells, mesangial cells, and immune cells of CKD
      rats with a 5/6 nephrectomy. The lung, liver, and heart tissue of CKD rats also
      overexpressed IL-20. Thus, we treated two tubular epithelial cells, TKPTS and M-1
      cells, with IL-20 to study its effects on CKD. IL-20 treatment induced apoptosis
      in these cells via caspase-3 activation. Incubating IL-20 with rat interstitial
      fibroblasts, NRK-49F cells, upregulated TGF-beta1 production, one key inducer for
      renal fibrogenesis. Therefore, IL-20 injured renal epithelial cells and induced
      fibroblasts to produce TGF-beta1 that hastened the progression of CKD.

PMID- 18639519
TI  - Dominant antigenic peptides located at the heavy chain terminal of botulinum
      neurotoxin B contain receptor-binding sites for synaptotagmin II.
AB  - Botulism toxicity is caused by botulinum neurotoxins (BoNTs) that bind to the
      surface of the nerve terminals through the C-terminal portion of the heavy chain
      (Hc) and gain access to the neuron cells, thereby blocking the release of
      neurotransmitters into the synapse by the light chain. It has been recently found
      that synaptotagmin II (syt II) is the specific protein receptor of BoNTs;
      however, the molecular basis underlying the interaction between BoNTs and the
      receptor has been poorly understood. In this study, the recombinant fragment from
      the luminal domain of the human protein receptor syt II was prepared. Further,
      the Hc antigenic peptides of BoNTs type B (BoNTb) containing the possible
      epitopes were synthesized and analyzed for checking their ability for specific
      recognition and binding by using completely protective polyclonal antibody and
      were then evaluated for checking their ability to elicit protective immunity in
      mice against lethal toxin challenge. Finally, the interaction between the Hc
      dominant antigenic peptides and syt II was analyzed. We found that two peptides
      located at the Hc terminal of the BoNTb showed the general character of the
      dominant antigenic epitopes in terms of protection against BoNTb intoxication.
      Further, they were found to contain the receptor-binding sites through the
      specific recognition of the receptor syt II. Both were derived from the
      uninterrupted segments of the amino acid residues H(1241-1277) of BoNTb. Kinetic
      data of the antigen-receptor interaction were depicted in real-time and
      calculated as affinity constant of 2.99x10(-7)M.

PMID- 18639520
TI  - IFN-gamma acts as anti-angiogenic cytokine in the human cornea by regulating the
      expression of VEGF-A and sVEGF-R1.
AB  - Inflammatory processes within the cornea are known to be associated with corneal
      neovascularization (CN). We examined the effects of inflammatory mediators on the
      expression of angiogenic factors by corneal cells. TNF-alpha and IL-1 induced
      VEGF-A secretion by corneal fibroblasts (HCRF) and this was inhibited
      significantly by IFN-gamma. Constitutively secreted VEGF-A by corneal epithelial
      cells (HCE) was not affected by these cytokines. Moreover, sVEGF-R1(sFlt-1)
      secretion by HCRF was stimulated significantly by IFN-gamma. JAK-STAT pathway
      inhibitor reversed the effects of IFN-gamma on VEGF-A and sFlt-1 secretion by
      HCRF. RT-PCR analysis showed that IFN-gamma influences the expression of VEGF-A
      and sFlt-1 by affecting their mRNA level. IFN-gamma inhibited TGF-beta induced
      VEGF-A secretion but not sVEGF-R1 secretion. This is the first report
      demonstrating the inhibitory and stimulatory effects of IFN-gamma on VEGF-A and
      sFlt-1 secretion, respectively. Our results suggest that IFN-gamma acts as an
      anti-angiogenic cytokine in the human cornea.

PMID- 18639521
TI  - Curcumin prevents human dendritic cell response to immune stimulants.
AB  - Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory
      and immunomodulatory properties, though the mechanism remains unclear. Dendritic
      cells (DCs) are important to generating an immune response and the effect of
      curcumin on human DCs has not been explored. The role curcumin in the DC response
      to bacterial and viral infection was investigated in vitro using LPS and Poly I:C
      as models of infection. CD14(+) monocytes, isolated from human peripheral blood,
      were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs.
      Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and
      functional assays were performed. Curcumin prevents DCs from responding to
      immunostimulants and inducing CD4(+) T cell proliferation by blocking maturation
      marker, cytokine and chemokine expression and reducing both migration and
      endocytosis. These data suggest a therapeutic role for curcumin as an immune
      suppressant.

PMID- 18639522
TI  - Effects of adiponectin on growth and differentiation of human keratinocytes-
      implication of impaired wound healing in diabetes.
AB  - Impaired wound healing is one of the most common complications associated with
      diabetes. Adiponectin is an abundant circulating adipocyte-derived cytokine that
      has beneficial effects on disorders accompanying diabetes. Herein we report that
      adiponectin has a regulatory effect on the growth and differentiation of HaCaT
      human keratinocyte cells. Furthermore, adiponectin regulated the expression of
      TGFbeta isoforms in keratinocytes in a dose-dependent manner, which implies that
      adiponectin modulates other types of cells related to wound repair via secretion
      of growth factors from keratinocytes. Moreover, TUNEL assay results revealed that
      adiponectin enhances apoptosis of keratinocytes. Taken together, the present
      results indicate that adiponectin has suppressive effects on the formation of
      hyperkeratosis commonly seen in patients with diabetic foot and its application
      may be beneficial for developing treatment for that disorder.

PMID- 18639523
TI  - SMT3IP1, a nucleolar SUMO-specific protease, deconjugates SUMO-2 from nucleolar
      and cytoplasmic nucleophosmin.
AB  - Sumoylation is reversibly regulated by SUMO-specific proteases. We characterized
      a nucleolar SUMO-specific protease, SMT3IP1, which has a preference for SUMO-2/3.
      To elucidate SMT3IP1 function, we screened for its interacting proteins that may
      be its substrates or regulate its activity. By using yeast two-hybrid screening,
      we identified nucleophosmin (NPM) as an SMT3IP1-binding partner. SMT3IP1 could
      preferentially remove SUMO-2 from sumoylated NPM. A catalytically inactive
      SMT3IP1 mutant increased intracellular accumulation of SUMO-2-modified NPM in a
      dominant-negative manner. Sumoylation of cytoplasmic mutated NPM was markedly
      elevated in an ARF-dependent manner. Despite the divergence in their
      localization, ectopic expression of SMT3IP1 could desumoylate a SUMO-2-modified
      NPM mutant. Additionally, genotoxic drugs caused the dissociation of NPM from
      nucleolar co-localization with SMT3IP1, but did not affect desumoylation of NPM
      by SMT3IP1. Our findings suggest that SMT3IP1-mediated desumoylation might
      control NPM physiological functions at both the nucleolus and other subcellular
      compartments.

PMID- 18639524
TI  - Podocalyxin expression in malignant astrocytic tumors.
AB  - Podocalyxin is an anti-adhesive mucin-like transmembrane sialoglycoprotein that
      has been implicated in the development of aggressive forms of cancer. Podocalyxin
      is also known as keratan sulfate (KS) proteoglycan. Recently, we revealed that
      highly sulfated KS or another mucin-like transmembrane sialoglycoprotein
      podoplanin/aggrus is upregulated in malignant astrocytic tumors. The aim of this
      study is to examine the relationship between podocalyxin expression and malignant
      progression of astrocytic tumors. In this study, 51 astrocytic tumors were
      investigated for podocalyxin expression using immunohistochemistry, Western blot
      analysis, and quantitative real-time PCR. Immunohistochemistry detected
      podocalyxin on the surface of tumor cells in six of 14 anaplastic astrocytomas
      (42.9%) and in 17 of 31 glioblastomas (54.8%), especially around proliferating
      endothelial cells. In diffuse astrocytoma, podocalyxin expression was observed
      only in vascular endothelial cells. Podocalyxin might be associated with the
      malignant progression of astrocytic tumors, and be a useful prognostic marker for
      astrocytic tumors.

PMID- 18639525
TI  - Regulation of Escherichia coli IscS desulfurase activity by ferrous iron and
      cysteine.
AB  - IscS plays a principal role in the synthesis of sulfur-containing biomolecules.
      It is known that the expression of iscS can be negatively regulated by IscR, the
      first gene product of iscRSUA-hscBA-fdx. What governs the regulation of cysteine
      desulfurase activity, however, is unknown. Here, we report that IscS from
      Escherichia coli is able to bind iron with an association constant of
      1.6x10(17)M(-1) to form an IscS-iron complex. IscS is also capable of binding
      both iron and sulfide to form an IscS-iron-sulfide complex with a higher
      affinity. The desulfurase activity is gradually inhibited as the amount of iron
      and sulfide bound to IscS increases. When 2Fe-2S binds IscS, about 20% of the
      activity is inhibited; when 8Fe-8S adheres to IscS, about 70% of the activity is
      inhibited. Thus, the cell is able to modulate its desulfurase activity with the
      formation of an IscS-iron-sulfide complex.

PMID- 18639526
TI  - Archvillin anchors in the Z-line of skeletal muscle via the nebulin C-terminus.
AB  - Z-Line of skeletal muscle is a complex protein network that likely plays an
      important role in signaling and muscle homeostasis. We used the yeast two-hybrid
      system to search for potential novel ligands of the Z-line portion of nebulin. We
      found that the C-terminal region of nebulin (residues 6457-6528) interacted with
      the C-terminus of archvillin (residues 1419-1687). Archvillin is a membrane
      skeletal protein that localizes to costameres, specialized adhesion sites in
      muscle. The binding sites between nebulin and archvillin were characterized using
      the yeast two-hybrid system, in vitro pull-down assays, and colocalization
      experiments in COS-7 cells. Our data suggest a model in which archvillin attaches
      directly to the Z-line through an interaction with the nebulin C-terminus. The
      interaction between nebulin and archvillin may provide a direct link between the
      sarcolemma and myofibrillar Z-lines.

PMID- 18639527
TI  - HIV-protease inhibitors block the enzymatic activity of purified Ste24p.
AB  - We reported that several HIV protease inhibitors (HIV-PIs) interfere with the
      endoproteolytic processing of two farnesylated proteins, yeast a-factor and
      mammalian prelamin A. We proposed that these drugs interfere with prelamin A
      processing by blocking ZMPSTE24, an integral membrane zinc metalloproteinase
      known to play a critical role in its processing. However, because all of the drug
      inhibition studies were performed with cultured fibroblasts or crude membrane
      fractions rather than on purified enzyme preparations, no definitive conclusions
      could be drawn. Here, we purified Ste24p, the yeast ortholog of ZMPSTE24, and
      showed that its enzymatic activity was blocked by three HIV-PIs (lopinavir,
      ritonavir, and tipranavir). A newer HIV-PI, darunavir, had little effect on
      Ste24p activity. None of the HIV-PIs had dramatic effects on the enzymatic
      activity of purified Ste14p, the prenylprotein methyltransferase. These studies
      strongly support our hypothesis that HIV-PIs block prelamin A processing by
      directly affecting the enzymatic activity of ZMPSTE24, and in this way they may
      contribute to lipodystrophy in individuals undergoing HIV-PI treatment.

PMID- 18639528
TI  - Expression of carboxylesterase and lipase genes in rat liver cell-types.
AB  - Approximately 80% of the body vitamin A is stored in liver stellate cells with in
      the lipid droplets as retinyl esters. In low vitamin A status or after liver
      injury, stellate cells are depleted of the stored retinyl esters by their
      hydrolysis to retinol. However, the identity of retinyl ester hydrolase(s)
      expressed in stellate cells is unknown. The expression of carboxylesterase and
      lipase genes in purified liver cell-types was investigated by real-time PCR. We
      found that six carboxylesterase and hepatic lipase genes were expressed in
      hepatocytes. Adipose triglyceride lipase was expressed in Kupffer cells, stellate
      cells and endothelial cells. Lipoprotein lipase expression was detected in
      Kupffer cells and stellate cells. As a function of stellate cell activation,
      expression of adipose triglyceride lipase decreased by twofold and lipoprotein
      lipase increased by 32-fold suggesting that it may play a role in retinol ester
      hydrolysis during stellate cell activation.

PMID- 18639529
TI  - Intersubunit and interprotein interactions of alpha- and beta-subunits of human
      eIF2: Effect of phosphorylation.
AB  - Purified recombinant human subunits of eukaryotic initiation factor 2 (eIF2)
      expressed in bacteria are found to interact with each other to form alphabeta,
      alphagamma, and betagamma complexes in a pull-down experiment. Recombinant
      phosphorylated human eIF2alpha that cannot interact with purified eIF2B, the
      GDP/GTP exchange factor of eIF2, however interacts efficiently with eIF2B along
      with the beta-subunit of eIF2 of the rabbit reticulocyte lysates and also with
      the purified recombinant beta-subunit. These findings therefore suggest that the
      beta-subunit of eIF2 mediates the productive and non-productive interactions
      between eIF2 and 2B. Recombinant alpha and beta-subunits serve as substrates for
      not only kinases but also for caspase 3 and interestingly phosphorylated subunits
      resist caspase action. Phosphorylation also modifies the beta-subunit's
      interaction with Nck1, a cofactor of eIF2alpha phosphatase, but not with eIF5,
      the GTPase activating protein. These findings suggest that subunits of mammalian
      eIF2 interact with each other and the beta-subunit plays a critical role both in
      the regulation and function of eIF2.

PMID- 18639530
TI  - In vivo chronic exposure to heroin or naltrexone selectively inhibits liver
      microsome formation of estradiol-3-glucuronide in the rat.
AB  - We have previously found that repeated exposure to heroin reduces liver synthesis
      of morphine-3-glucuronide (M3G) and increases the production of morphine-6
      glucuronide (M6G), which normally is not formed in the rat. By contrast repeated
      exposure to naltrexone does not activate M6G synthesis but increases the V(max)
      of M3G formation. M3G synthesis depends on the activity of two isoforms of the
      UDP-glucuronosyltransferase (UGT), UGT1A1 and UGT2B1. These isozymes also
      activate the formation of estradiol-3-glucuronide (E3G) and estradiol-17
      glucuronide (E17G), respectively. The goal of the present study was to
      investigate the role of UGT1A1 and UGT2B1 in the effects of heroin and naltrexone
      by determining their influence on the synthesis of E3G and E17G. Estradiol
      glucuronidation was performed using microsomes of rats treated daily, for 10
      days, with saline, heroin (10mg/kg, i.p.), or naltrexone (40mg/kg, i.p.).
      Moreover, liver expression of both UGT1A1 and UGT2B1 was studied in the same
      experimental conditions by polymerase chain reaction analysis. Kinetic analysis
      showed that the V(max) for E3G formation was significantly reduced by both heroin
      (168.82+/-9.73nmol/mg/min) and naltrexone (194.60+/-16.6) relative to saline
      (624.60+/-17.6). Moreover, homotropic kinetic of E3G formation (Hill coefficient:
      1.8) was transformed in Michaelis-Menten kinetic by both heroin (0.88) and
      naltrexone (1.15). The synthesis of E17G was not affected by either opioid. The
      expression of liver UGT1A1 and UGT2B1 did not differ across groups. The present
      results suggest that heroin and naltrexone can reduce estradiol glucuronidation
      via a specific interaction with UGT1A1 isoform.

PMID- 18639531
TI  - A comparative study of the effects of quercetin and its glucuronide and sulfate
      metabolites on human neutrophil function in vitro.
AB  - Exposure of neutrophils to either lipopolysaccharide (LPS) or N-formyl-methionyl
      leucyl-phenylalanine (fMLP) is associated with changes in the expression of cell
      adhesion molecules and elevation of intracellular calcium ions. Although dietary
      flavonoids are reported to possess anti-inflammatory properties, little is known
      regarding the effect of their metabolites. We have investigated the effects of
      quercetin and its major metabolites on LPS and fMLP-stimulated human neutrophils
      using concentrations comparable to those reported in feeding studies on human
      volunteers. The metabolite quercetin 3-glucuronide caused a significant reduction
      in fMLP-evoked calcium influx in human neutrophils (approximately 35%), while
      neither quercetin 3'-sulfate nor quercetin produced a similar change. Acute
      exposure of human neutrophils to LPS altered cell shape and surface expression of
      CD16, but neither of these events were significantly altered by quercetin,
      quercetin 3-glucuronide nor quercetin 3'-sulfate. In addition, LPS caused a
      fivefold up-regulation in the expression of beta(2)-integrin (CD11b/Mac 1) and a
      concomitant 70% down-regulation of L-selectin (CD62L) adhesion molecule
      expression in human neutrophils. Neither effect was altered by quercetin,
      quercetin 3-glucuronide or quercetin 3'-sulfate. In conclusion, we found that
      acute exposure to quercetin and quercetin 3'-sulfate does not affect either
      expression of cell adhesion molecules or the elevation of intracellular calcium
      ions in response to LPS and fMLP in human neutrophils. However, quercetin 3
      glucuronide reduced fMLP-evoked calcium responses. While this study highlights
      that metabolites of quercetin may possess different biological properties,
      dietary ingestion of quercetin is unlikely to exert a major effect on neutrophil
      function in vivo.

PMID- 18639532
TI  - Nitric oxide associated with iNOS expression inhibits acetylcholinesterase
      activity and induces memory impairment during acute hypobaric hypoxia.
AB  - The mechanisms responsible for cholinergic dysfunction associated learning and
      memory impairment during hypoxia are not well-understood. However it is known
      that inflammatory mediators like inducible nitric oxide synthase (iNOS) hamper
      the functions of cholinergic neurons. In this present experiment we made an
      effort to study the iNOS expression mediated retrograde and anterograde memory
      impairment in Balb/c mice following acute hypobaric hypoxia (at an altitude of
      23,000ft for 6h) using elevated plus maze and passive avoidance step-through
      tasks. Our results demonstrated that hypoxia transiently impairs the retrograde
      memory without affecting the anterograde memory functions, accompanied with a
      substantial rise in iNOS expression and nitric oxide levels in cerebral cortex on
      days 2 and 3 post hypoxia. Treatment with aminoguanidine (iNOS inhibitor ),
      resulted in down-regulation of the iNOS expression, attenuation of the surge of
      nitric oxide (NO) in cerebral cortex and reversal of retrograde memory impairment
      due to hypoxia. Moreover the reduced AChE activity and elevated lipid
      peroxidation in cerebral cortex were evident during post hypoxia re-oxygenation
      period, which was not observed in the hippocampus. Additionally, NO donor
      spermine NONOate could inhibit the AChE activity in brain homogenates in a
      concentration-dependent manner, which further substantiate that nitric oxide
      produced during post hypoxia re-oxygenation, primarily contributes to the
      observed inhibition of cortical AChE activity. Based on these experiments we
      hypothesize that the NO burst as a result of iNOS upregulation during hypoxia
      interrupts the memory consolidation by altering the cholinergic functions.

PMID- 18639533
TI  - Anxiety and oscillatory responses to emotional facial expressions.
AB  - In the last decade, event-related potential and functional magnetic resonance
      imaging studies were very useful in temporal and spatial localization of brain
      processes involved in the recognition of emotional facial expressions. However,
      frequency characteristics of the underlying processes have been less studied.
      Besides, most of the studies did not take into account personality-related
      individual differences. In this study, effects of explicit and implicit anxiety
      on the oscillatory dynamics of cortical responses elicited by presentation of
      angry, neutral, and happy faces were investigated using time-frequency
      decomposition by means of wavelet transform. Both explicit and implicit anxiety
      were associated with higher alpha band desynchronization, which was most
      pronounced during presentation of angry faces. Within theta and delta bands,
      effects appeared to be opposite for explicit and implicit anxiety measures. In
      implicitly anxious subjects, frontal delta and theta synchronization upon the
      presentation of angry and happy (but not neutral) faces was found to be higher
      than in low anxiety ones, whereas explicit anxiety was associated with a lower
      theta band synchronization. The results are discussed in terms of conscious and
      controlled vs. unconscious and intuitive information processing associated with
      explicit and implicit personality measures.

PMID- 18639534
TI  - Signaling pathway of glutamate in the vestibular nuclei following acute
      hypotension in rats.
AB  - Acute hypotension induces excitation of electrical activity and expression of c
      Fos protein and phosphorylated extracellular signal-regulated kinase (pERK) in
      the vestibular nuclei. Expression of c-Fos protein and pERK is mediated by the
      excitatory neurotransmitter, glutamate. In this study, in order to investigate
      the signaling pathway of glutamate in the vestibular nuclei following acute
      hypotension, expression of the NR2B subunit of glutamate N-methyl-D-aspartate
      (NMDA) receptors and the GluR1 subunit of glutamate alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) receptors was measured by Western
      blotting in the medial vestibular nucleus (MVN) following acute hypotension in
      bilateral labyrinthectomized (BL) rats. In intact labyrinthine animals, acute
      hypotension increased expression of pGluR1 and pNR2B in the MVN. Expression of
      pGluR1 Ser831 and Ser845 peaked at 5 and 30 min after acute hypotension and
      expression of pNR2B peaked at 60 min after acute hypotension, respectively. In BL
      animals, expression of pGluR1 Ser831, pGluR1 Ser845, and pNR2B was decreased
      significantly compared to intact labyrinthine animals following acute
      hypotension. These results suggest that excitatory afferent signals from the
      peripheral vestibular receptors, resulting from acute hypotension, release
      glutamate into postsynaptic neurons in the vestibular nuclei and the excitatory
      signals are transmitted through the GluR1 subunit of the AMPA receptors and the
      NR2B subunits of the NMDA receptors in the vestibular system.

PMID- 18639535
TI  - Blockade of EphB2 enhances neurogenesis in the subventricular zone and improves
      neurological function after cerebral cortical infarction in hypertensive rats.
AB  - EphB2/ephrinBs has been recently demonstrated to regulate cell proliferation in
      the neurogenic subventricular zone (SVZ). However, little is known about the role
      of EphB2 in adult neurogenesis following cerebral infarction. In the present
      study, we investigated the role of EphB2 in proliferation and differentiation of
      precursor cells within the SVZ, as well as the neurological function recovery
      after permanent middle cerebral artery occlusion (MCAO) in hypertensive rats.
      Bromodeoxyuridine (BrdU) was given twice per day starting from 24h after MCAO for
      6-consecutive days. Recombinant EphB2-Fc or IgG-Fc was preclustered by incubation
      with anti-human Fcgamma and then intraventricularly administrated at 24h after
      MCAO. The neurological function was evaluated before operation and at 7, 14 and
      21 days after MCAO respectively. The infarct size and immunoreactivities of BrdU,
      Nestin, DCX, GFAP and NeuN were measured at 7, 14 and 21 days after MCAO
      respectively. Treatment with EphB2-Fc markedly improved the neurological function
      recovery within 3 weeks after MCAO. In parallel, EphB2-Fc significantly increased
      the number of BrdU-labeled cells and led to marked increases in BrdU+/DCX+ and
      BrdU+/Nestin+ cells within the ipsilateral SVZ for 2 weeks after MCAO
      respectively (all p < 0.05). The BrdU+/NeuN+ cells in the peri-infarct area and
      neighboring ipsilateral striatum were significantly increased following EphB2-Fc
      infusion within 3 weeks after MCAO (all p < 0.05). Our data suggest that
      administration of exogenous clustered EphB2-Fc at 24h can enhance the endogenous
      neurogenesis and concomitantly improve neurological recovery after cerebral
      infarction.

PMID- 18639536
TI  - fMRI characterization of the language formulation area.
AB  - Participants read sentences presented one word at a time, half of which ended
      with a semantically incongruent ending. 1.5T functional magnetic resonance
      imaging data were collected from 11 participants, showing that the left posterior
      inferior temporal region, which has previously been termed the Language
      Formulation Area (LFA), responded to cloze probability. It is suggested, based on
      anatomical positioning and a literature review, that the responsiveness of the
      LFA to cloze probabilities may reflect a role in coordinating the lexical and non
      lexical reading pathways. Finally, it is noted that previous studies have
      implicated this region in dyslexia and some speculations are made in this regard.

PMID- 18639537
TI  - Differences in surface behaviour of galactolipoids originating from different
      kind of wheat tissue cultivated in vitro.
AB  - The aim of presented researches was to investigate the physicochemical properties
      of Langmuir monolayer of galactolipids extracted from two different kinds of
      plastids: immature embryos and inflorescences. Differences between the
      physicochemical properties of the plastid membranes may help to explain different
      physiological processes, such as plant regeneration. Surface pressure (pi) vs.
      molecular area (A) isotherms of the monogalactosyldiacylglycerol
      (MGDG)/digalactosyldiacylglycerol (DGDG) monolayers of various molar ratios were
      measured at 15 degrees C. Galactolipids were extracted from two different types
      of tissue: inflorescences and embryos. Based on the analysis of the pi-A
      isotherms, the properties of monolayers, such as collapse pressure (pi(coll)),
      limiting area (A(lim)), compressibility modulus (C(s)(-1)), excess free energy of
      mixing (DeltaG(EXC)) and free energy of mixing (DeltaG(MIX)), were calculated.
      The results show that pure MGDG and DGDG and their mixtures form liquid-expanded
      monolayers, independently on the kind of tissue. Galactolipids originating from
      inflorescences produce more compressible films at the air/water interface, with
      larger limiting area per molecule and lower stability against the collapse
      process. MGDG and DGDG are miscible and form non-ideal mixed monolayers at the
      air/water interface. Negative values of DeltaG(EXC) were calculated for the
      mixture of galactolipids originating from inflorescences, with the content of
      MGDG, x(MGDG)>0.6. In the case of embryos, the negative values of DeltaG(EXC)
      were found for x(MGDG) approximately 0.5. Therefore, the attractive interactions
      between MGDG and DGDG exist in the mixtures of these compositions. As it is shown
      by negative values of DeltaG(MIX), mixed monolayers are more stable compared with
      unmixed ones.

PMID- 18639538
TI  - Temporal switching of regulation and function of eye gone (eyg) in Drosophila eye
      development.
AB  - The Pax gene eyg is important for Drosophila eye development. eyg expression in
      the visual system changes dynamically during development. In this study, we found
      that the transcriptional regulation of eyg can be separated into four distinct
      temporal phases (E, L1, L2, and L3) and each is regulated by distinct cis
      regulatory elements. Utilizing these enhancers for temporal and spatially
      specific manipulations, we addressed the regulation and function of eyg at
      different developmental stages. We found that Notch signaling is required and
      sufficient for eyg expression and this activity is restricted only to the L2
      stage. We further showed that the function of eyg in eye development is required
      only at the second instar larval stage, while its function for head and antenna
      development can be provided at any time during embryo and larval development.
      Thus there is a temporal switch of the regulatory mechanism and function of eyg.
      We propose that eyg expression at L2 is induced and maintained by N signaling,
      and is turned off at L3 by a negative feedback loop involving the morphogenetic
      furrow.

PMID- 18639540
TI  - Securin and not CDK1/cyclin B1 regulates sister chromatid disjunction during
      meiosis II in mouse eggs.
AB  - Mammalian eggs remain arrested at metaphase of the second meiotic division
      (metII) for an indeterminate time before fertilization. During this period, which
      can last several hours, the continued attachment of sister chromatids is thought
      to be achieved by inhibition of the protease separase. Separase is known to be
      inhibited by binding either securin or Maturation (M-Phase)-Promoting Factor, a
      heterodimer of CDK1/cyclin B1. However, the relative contribution of securin and
      CDK/cyclin B1 to sister chromatid attachment during metII arrest has not been
      assessed. Although there are conditions in which either CDK1/cyclinB1 activity or
      securin can prevent sister chromatid disjunction, principally by overexpression
      of non-degradable cyclin B1 or securin, we find here that separase activity is
      primarily regulated by securin and not CDK1/cyclin B1. Thus the CDK1 inhibitor
      roscovitine and an antibody we designed to block the interaction of CDK1/cyclin
      B1 with separase, both failed to induce sister disjunction. In contrast, securin
      morpholino knockdown specifically induced loss of sister attachment, that could
      be restored by securin cRNA rescue. During metII arrest separase appears
      primarily regulated by securin binding, not CDK1/cyclin B1.

PMID- 18639539
TI  - Reiterative roles for FGF signaling in the establishment of size and proportion
      of the zebrafish heart.
AB  - Development of a functional organ requires the establishment of its proper size
      as well as the establishment of the relative proportions of its individual
      components. In the zebrafish heart, organ size and proportion depend heavily on
      the number of cells in each of its two major chambers, the ventricle and the
      atrium. Heart size and chamber proportionality are both affected in zebrafish
      fgf8 mutants. To determine when and how FGF signaling influences these
      characteristics, we examined the effect of temporally controlled pathway
      inhibition. During cardiac specification, reduction of FGF signaling inhibits
      formation of both ventricular and atrial cardiomyocytes, with a stronger impact
      on ventricular cells. After cardiomyocyte differentiation begins, reduction of
      FGF signaling can still result in a deficiency of ventricular cardiomyocytes.
      Consistent with two temporally distinct roles for FGF, we find that increased FGF
      signaling induces a cardiomyocyte surplus only before cardiac differentiation
      begins. Thus, FGF signaling first regulates heart size and chamber
      proportionality during cardiac specification and later refines ventricular
      proportion by regulating cell number after the onset of differentiation.
      Together, our data demonstrate that a single signaling pathway can act
      reiteratively to coordinate organ size and proportion.

PMID- 18639541
TI  - Effects of lactone derivatives on aromatase (CYP19) activity in H295R human
      adrenocortical and (anti)androgenicity in transfected LNCaP human prostate cancer
      cells.
AB  - Certain lactone-containing secondary plant metabolites display potent biological
      effects, including anti-tumor activities. This is of particular interest as these
      compounds appear effective against hormone-dependent cancers, such as those of
      breast and prostate, of which the incidence is on the rise. The mechanisms of
      anti-tumor action of these compounds are largely unknown. Thirteen synthetic
      lactone derivatives were evaluated for effects on aromatase activity and mRNA
      expression in H295R human adrenocortical carcinoma cells. Aromatase (CYP19) is a
      key enzyme in the synthesis of estrogens from androgens. Over-expression has been
      associated with increased risk of developing estrogen-dependent mammary tumors,
      and aromatase inhibitors are effective in their treatment. The androgen receptor
      is implicated in mediating hormone-dependent prostate tumor growth, and androgen
      antagonists are effective in the treatment of these cancers. Thus the
      (anti)androgenic effects of the lactones were also assessed in LNCaP human
      prostate cancer cells transfected with human androgen receptor and an androgen
      receptor-responsive luciferase reporter gene. Cells were exposed to lactones (0.1
      100 microM) dissolved in dimethyl sulfoxide (0.1% in medium) for 24 h prior to
      measurement of aromatase activity using a tritiated water-release assay. Three
      (competitive) inhibitors of aromatase activity were identified (potencies in
      decreasing order): 3-(3,4-dimethoxy-phenyl)-4-(4-methoxy-phenyl)-5H-furan-2-one
      (CRI-7; IC(50)=1 microM; K(i)=1.0 microM), 3,4-bis-(3,4-dimethoxy-phenyl)-5H
      furan-2-one (CRI-8; IC(50)=2 microM; K(i)=1.2 microM) and 3-(3,4-dimethoxy
      phenyl)-4-(3,4,5-trimethoxy-phenyl)-5H-furan-2-one (CRI-9; IC(50)=3 microM;
      K(i)=6.8 microM). Several concentration-dependent inducers of aromatase (>2fold)
      were also identified (CRI-1, CRI-4 or Vioxx, CRI-11 and CRI-13). These lactones
      also induced pII promoter-specific CYP19 transcripts. In transfected LNCaP cells,
      the three aromatase inhibitors CRI-7, 8 and 9 demonstrated concentration
      dependent anti-androgenicity above 0.1 microM in the presence of either 0.1 nM of
      dihydrotestosterone or the synthetic androgen R1881. The other lactones showed no
      consistent pro- or anti-androgenic effects in these LNCaP cells. Lactone moiety
      containing molecules may form the structural basis for the development of potent
      drugs effective against hormone-dependent cancers.

PMID- 18639542
TI  - Cloning and pharmacological characterization of the dog histamine H4 receptor.
AB  - The histamine H4 receptor has been shown to have a role in chemotaxis and
      mediator release in various types of immune cells and has been implicated in
      mediating inflammation in vivo. Previous work has shown that there were
      differences in the histamine H4 receptor sequence of different species and these
      translated into changes in the pharmacology of the receptors. To help further
      understand the nature of these differences, we have cloned and expressed the
      histamine H4 receptor of dog (Canis familiaris). The dog histamine H4 receptor
      has a 61-71% homology with the receptors from other species, with a 71% homology
      to the human receptor. The affinity for histamine at the dog histamine H4
      receptor is 18 nM and is 3-fold lower than the human ortholog. A number of
      previously described histamine H4 receptor ligands were tested for affinity at
      the dog histamine H4 receptor and histamine showed the highest affinity of the
      ligands tested. In addition, the histamine H4 receptor selective antagonist, JNJ
      7777120, had a Ki value of 50 nM and acts as an antagonist at the dog receptor.
      In general, agonists of the human histamine H4 receptor were also agonists of the
      dog receptor albeit with different efficacy levels. The cloning and in vitro
      pharmacological characterization of the dog histamine H4 receptor provide useful
      information for future studies using dog models as well as in understanding the
      ligand-receptor interactions of the receptor.

PMID- 18639543
TI  - A quassinoid 6alpha-tigloyloxychaparrinone inhibits hypoxia-inducible factor-1
      pathway by inhibition of eukaryotic translation initiation factor 4E
      phosphorylation.
AB  - Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses
      to low oxygen and vital to many aspects of cancer biology. In a search for HIF-1
      inhibitors, we identified a quassinoid 6alpha-tigloyloxychaparrinone (TCN) as an
      inhibitor of HIF-1 activation from Ailantus altissima. We here demonstrated the
      effect of TCN on HIF-1 activation induced by hypoxia or CoCl2. TCN showed the
      potent inhibitory activity against HIF-1 activation induced by hypoxia in various
      human cancer cell lines. This compound markedly decreased the hypoxia-induced
      accumulation of HIF-1alpha protein dose-dependently, whereas it did not affect
      the expressions of HIF-1beta and topoisomerase-I. Furthermore, TCN prevented
      hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth
      factor (VEGF) and erythropoietin. Further analysis revealed that TCN strongly
      inhibited HIF-1alpha protein synthesis, without affecting the expression level of
      HIF-1alpha mRNA or degradation of HIF-1alpha protein. Moreover, the levels of
      phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), mitogen
      activated protein (MAP) kinase-interacting protein kinase-1 (MNK1) and eukaryotic
      initiation factor 4E (eIF4E) were significantly suppressed by the treatment of
      TCN, without changing the total levels of these proteins. Our data suggested that
      TCN may exhibit anticancer activity by inhibiting HIF-1alpha translation through
      the inhibition of eIF4E phosphorylation pathway and thus provide a novel
      mechanism for the anticancer activity of quassinoids. TCN could be a new HIF-1
      targeted anticancer agent and be effective on mammalian target of rapamycin
      (mTOR)-targeted cancer therapy, in which mTOR inhibition increases eIF4E
      phosphorylation.

PMID- 18639544
TI  - 6,3'-Dinitroflavone is a low efficacy modulator of GABA(A) receptors.
AB  - 6,3'-Dinitroflavone (6,3'-DNF) is a synthetic flavone derivative that exerts
      anxiolytic effects in the elevated plus maze. Based on the finding that this
      effect is blocked by Ro15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H
      imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate) which is a specific antagonist
      at the benzodiazepine binding site of GABA(A) receptors we investigated the
      interaction of 6,3'-DNF with several recombinant GABA(A) receptor subtypes.
      Inhibition of [(3)H]flunitrazepam binding to recombinant GABA(A) receptors in
      transiently transfected HEK293 cells indicated that 6,3'-DNF exhibited the
      highest affinity for GABA(A) receptors composed of alpha1beta2gamma2 subunits and
      a 2-20 fold lower affinity for homologous receptors containing alpha2, alpha3, or
      alpha5 subunits. Two-electrode voltage-clamp experiments in Xenopus oocytes
      indicated that 6,3'-DNF does not induce chloride flux in the absence of GABA, but
      exerts low efficacy inverse agonistic modulatory effects on GABA-elicited
      currents in the GABA(A) receptor subtypes alpha1beta2gamma2 and
      alpha5beta2gamma2. In the subtypes alpha2beta2gamma2, alpha3beta2gamma2,
      alpha4beta2gamma2, alpha6beta2gamma2 or alpha4beta2delta and alpha4beta3delta,
      6,3'-DNF exerts either none or very low efficacy positive modulatory effects. In
      contrast, 100 nM Ro15-1788 exhibited weak to moderate partial agonistic effects
      on each receptor investigated. These data indicate that Ro15-1788 only can
      antagonize the weak inverse agonist effects of 6,3'-DNF on alpha1beta2gamma2 and
      alpha5beta2gamma2 receptors, but will enhance the weak agonistic effects on the
      other receptor subtypes investigated. The possible mechanism of the Ro15-1788
      sensitive anxiolytic effect of 6,3'-DNF is discussed.

PMID- 18639545
TI  - ATAD 3A and ATAD 3B are distal 1p-located genes differentially expressed in human
      glioma cell lines and present in vitro anti-oncogenic and chemoresistant
      properties.
AB  - Human oligodendrogliomas are chemosensitive gliomas usually characterized by a
      loss of heterozygosity in the large distal regions of the short arm of chromosome
      1 (1p LOH). Chemoresistant astrocytomas do not have this genetic signature,
      suggesting that the 1p arms may contain anti-oncogene and/or genes enabling
      chemoresistance. We have focused here on two human 1p-distal genes, ATAD 3A and
      ATAD 3B (1p36-33), and analyzed their gene products in normal human cell lines
      and tissues and in glioma-derived human cell lines. Using specific anti-peptide
      antibodies, we have found that ATAD 3A is ubiquitously expressed, whereas ATAD 3B
      is expressed in embryonic tissues, adult germinative zone and in astrocytoma cell
      lines but it is not expressed in oligodendroglioma cell lines or in the adult
      cortex. Furthermore, we have found that human glioma cell lines overexpressing or
      underexpressing ATAD 3A and ATAD 3B, show modified cell growth, anchorage
      independent growth, and chemoresistance to doxorubicin and other genotoxic drugs.
      These results demonstrate the potential for ATAD 3B as a putative marker in
      discriminating astrocytomas from oligodendrogliomas. We also have shown that the
      loss of ATAD 3A/3B may be involved in the transformation pathway and the
      chemosensitivity of oligodendrogliomas.

PMID- 18639546
TI  - GD-DTPA enhanced MRI of ocular transport in a rat model of chronic glaucoma.
AB  - Glaucoma is a neurodegenerative disease of the visual system characterized by the
      elevation of intraocular pressure. While this elevated pressure is related to an
      increased resistance to the outflow of aqueous humor from the eye, their impacts
      to the etiology and pathogenesis of the disease are not fully understood. This
      study aims to employ in vivo Gd-DTPA enhanced magnetic resonance imaging to
      evaluate the ocular transport following an induction of ocular hypertension in a
      rat model of chronic glaucoma. An experimental ocular hypertension model was
      induced in adult rats using an argon laser to photocoagulate the episcleral and
      limbal veins on the surface of the eyeball. The enhancements of the MRI signal
      intensity in the anterior chamber and vitreous body were measured as a function
      of time following systemic administration of Gd-DTPA solution at 3 mmol/kg.
      Results showed a progressive T1-weighted signal increase in the vitreous body of
      the glaucomatous eye but not the control eye. This increase occurred earlier in
      the anterior vitreous body than the preretinal vitreous. Further, there was an
      earlier Gd-DTPA transport into the anterior chamber in the majority of
      glaucomatous eyes. Our findings revealed the leakage of Gd-DTPA at the aqueous
      vitreous interface, which was likely resulted from increased permeability of
      blood-aqueous or aqueous-vitreous barrier. These may explain the sources of
      changing biochemical compositions in the glaucomatous chamber components, which
      may implicate the cascades of neurodegenerative processes in the retina and the
      optic nerve.

PMID- 18639547
TI  - Molecular and histological changes following central retinal artery occlusion in
      a mouse model.
AB  - The aim of this study was to characterize the molecular and histological changes
      that occur in the retina following central retinal artery occlusion (CRAO) in a
      mouse model. CRAO was induced in 60 mice by laser photoactivation of
      intravenously injected rose bengal. Mice were sacrificed at 3, 6, 12, and 24h and
      7 and 21 days after CRAO induction for molecular analysis (5-13 mice/time point)
      and histological and apoptosis studies (3-4 mice/time point). Fundus examination
      and fluorescein angiography were also performed at various points. Retinal mRNA
      was analyzed for expression of T-cell antigen 1 (Thy-1), vascular endothelial
      growth factor (VEGF), heme oxygenase-1 (HO-1), and hypoxia-induced factor 1 alpha
      (HIF-1 alpha) using real-time polymerase chain reaction. The results showed that
      at 6-24h following CRAO induction, the retina was edematous, with interrupted
      blood perfusion. Fluorescein angiography showed reperfusion at 6h, and TdT
      mediated dUTP nick end-labeling (TUNEL) assay revealed an increase in apoptotic
      cells in the first 24h. On histological sections, nuclear loss in the inner
      retinal layers was maximal on day 21. Thy-1 expression decreased to 30% of
      baseline (P<or=0.002). VEGF expression increased in the first 3h and gradually
      decreased thereafter, reaching 75% of baseline on day 21 (P<or=0.005). HO-1 was
      upregulated at all time points, with a peak at 12h. No change was noted in HIF-1
      alpha expression at any time. In conclusion, CRAO in mice causes cell apoptosis
      in the inner layers of the retina, with a significant cell loss and a decrease in
      Thy-1 expression by 21 days. These changes are accompanied by a rise in
      expression of the ischemia-related protein HO-1 to a peak at 12h, with levels
      remaining above control values at day 21. Given the similarity of the mouse model
      to human CRAO, these findings may have implications for the future clinical
      management of CRAO.

PMID- 18639548
TI  - Myogel supports the ex-vivo amplification of corneal epithelial cells.
AB  - Limbal stem cell deficiency leads to conjunctivalisation of the cornea and
      subsequent loss of vision. The recent development of transplantation of ex-vivo
      amplified corneal epithelium, derived from limbal stem cells, has shown promise
      in treating this challenging condition. The purpose of this research was to
      compare a variety of cell sheet carriers for their suitability in creating a
      confluent corneal epithelium from amplified limbal stem cells. Cadaveric donor
      limbal cells were cultured using an explant technique, free of 3T3 feeder cells,
      on a variety of cell sheet carriers, including denuded amniotic membrane,
      Matrigel, Myogel and stromal extract. Comparisons in rate of growth and degree of
      differentiation were made, using immunocytochemistry (CK3, CK19 and ABCG2). The
      most rapid growth was observed on Myogel and denuded amniotic membrane, these two
      cell carriers also provided the most reliable substrata for achieving confluence.
      The putative limbal stem cell marker, ABCG2, stained positively on cells grown
      over Myogel and Matrigel but not for those propagated on denuded amniotic
      membrane. In the clinical setting amniotic membrane has been demonstrated to
      provide a suitable carrier for limbal stem cells and the resultant epithelium has
      been shown to be successful in treating limbal stem cell deficiency. Myogel may
      provide an alternative cell carrier with a further reduction in risk as it is has
      the potential to be derived from an autologous muscle biopsy in the clinical
      setting.

PMID- 18639549
TI  - Distinctive biochemistry in the trypanosome mitochondrial intermembrane space
      suggests a model for stepwise evolution of the MIA pathway for import of cysteine
      rich proteins.
AB  - Mia40-dependent disulphide bond exchange is used by animals, yeast, and probably
      plants for import of small, cysteine-rich proteins into the mitochondrial
      intermembrane space (IMS). During import, electrons are transferred from the
      imported substrate to Mia40 then, via the sulphydryl oxidase Erv1, into the
      respiratory chain. Curiously, however, there are protozoa which contain
      substrates for Mia40-dependent import, but lack Mia40. There are also organisms
      where Erv1 is present in the absence of respiratory chain components. In
      accommodating these and other relevant observations pertaining to mitochondrial
      cell biology, we hypothesise that the ancestral IMS import pathway for disulphide
      bonded proteins required only Erv1 (but not Mia40) and identify parasites in
      which O(2) is the likely physiological oxidant for Erv1.

PMID- 18639550
TI  - High-resolution manometry and impedance-pH/manometry: valuable tools in clinical
      and investigational esophagology.
AB  - Both high-resolution manometry (HRM) and impedance-pH/manometry monitoring have
      established themselves as research tools and both are now emerging in the
      clinical arena. Solid-state HRM capable of simultaneously monitoring the entire
      pressure profile from the pharynx to the stomach along with pressure topography
      plotting represents an evolution in esophageal manometry. Two strengths of HRM
      with pressure topography plots compared with conventional manometric recordings
      are (1) accurately delineating and tracking the movement of functionally defined
      contractile elements of the esophagus and its sphincters, and (2) easily
      distinguishing between luminal pressurization attributable to spastic
      contractions and that resultant from a trapped bolus in a dysfunctional
      esophagus. Making these distinctions objectifies the identification of achalasia,
      distal esophageal spasm, functional obstruction, and subtypes thereof. Ambulatory
      intraluminal impedance pH monitoring has opened our eyes to the trafficking of
      much more than acid reflux through the esophageal lumen. It is clear that acid
      reflux as identified by a conventional pH electrode represents only a subset of
      reflux events with many more reflux episodes being composed of less acidic and
      gaseous mixtures. This has prompted many investigations into the genesis of
      refractory reflux symptoms. However, with both technologies, the challenge has
      been to make sense of the vastly expanded datasets. At the very least, HRM is a
      major technological tweak on conventional manometry, and impedance pH monitoring
      yields information above and beyond that gained from conventional pH monitoring
      studies. Ultimately, however, both technologies will be strengthened as outcome
      studies evaluating their utilization become available.

PMID- 18639551
TI  - Androgen receptor is a new potential therapeutic target for the treatment of
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Androgen effects on hepatocellular carcinoma (HCC) remain
      controversial and androgen ablation therapy to treat HCC also leads to
      inconsistent results. Here we examine androgen receptor (AR) roles in
      hepatocarcinogenesis using mice lacking AR in hepatocytes. METHODS: By using the
      Cre-Lox conditional knockout mice model injected with carcinogen, we examined the
      AR roles in hepatocarcinogenesis. We also tested the possible roles of AR in
      cellular oxidative stress and DNA damage sensing/repairing systems. By using AR
      degrading compound, ASC-J9, or AR-small interference RNA, we also examined the
      therapeutic potentials of targeting AR in HCC. RESULTS: We found AR expression
      was increased in human HCC compared with normal livers. We also found mice
      lacking hepatic AR developed later and less HCC than their wild-type littermates
      with comparable serum testosterone in both male and female mice. Addition of
      functional AR in human HCC cells also resulted in the promotion of cell growth in
      the absence or presence of 5alpha-dihydrotestosterone. Mechanistic dissection
      suggests that AR may promote hepatocarcinogenesis via increased cellular
      oxidative stress and DNA damage, as well as suppression of p53-mediated DNA
      damage sensing/repairing system and cell apoptosis. Targeting AR directly via
      either AR-small interference RNA or ASC-J9 resulted in suppression of HCC in both
      ex vivo cell lines and in vivo mice models. CONCLUSIONS: Our data point to AR,
      but not androgens, as a potential new and better therapeutic target for the
      battle of HCC.

PMID- 18639552
TI  - Genetic variants in major histocompatibility complex-linked genes associate with
      pediatric liver transplant rejection.
AB  - BACKGROUND & AIMS: Limited access to large samples precludes genome-wide
      association studies of rare but complex traits. To localize candidate genes with
      family-based genome-wide association, a novel exploratory analysis was first
      tested on 1774 major histocompatibility complex single nucleotide polymorphisms
      (SNPs) in 240 DNA samples from 80 children with primary liver transplantation and
      their biologic parents. METHODS: Initially, 57 SNPs with large differences (P <
      .05) in minor allele frequencies were selected when parents of children with
      early rejection (rejectors) were compared with parents of nonrejectors. RESULTS:
      In hypothesis testing of selected SNPs, the gamete competition statistic
      identified the minor allele G of the SNP rs9296068, near HLA-DOA, as being
      significantly different (P = .018) between outcome groups in parent-to-child
      transmission. Subsequent simple association testing confirmed over- and
      undertransmission of rs9296068 based on the most significant differences between
      outcome groups, of 1774 SNPs tested (P = .002), and allele (G) frequencies that
      were greater among rejectors (51.4% vs 36.8%, respectively, P = .015) and lower
      among nonrejectors (26.8% vs 36.8%, respectively, P = .074) compared with 400
      normal control Caucasian children. In early functional validation, rejectors
      demonstrated significant repression of the first HLA-DOA exon closest to
      rs9296068. Also, intragraft B lymphocytes, whose antigen-presenting function is
      selectively inhibited by HLA-DOA were 3-fold more numerous during rejection among
      rejectors with the risk allele, than those without. CONCLUSIONS: The minor allele
      of the SNP rs9296068 is significantly associated with liver transplantation
      rejection and with enhanced B-lymphocyte participation in rejection, likely
      because of a dysfunctional HLA-DOA gene product.

PMID- 18639553
TI  - Molecular imaging of murine intestinal inflammation with 2-deoxy-2-[18F]fluoro-D
      glucose and positron emission tomography.
AB  - BACKGROUND & AIMS: 2-Deoxy-2-[(18)F]fluoro-d-glucose (FDG) uptake by positron
      emission tomography (PET), a measure of glucose transporter activity, has been
      used to detect mucosal inflammation. However, there is limited understanding of
      the biologic basis of mucosal FDG uptake. METHODS: A contrast-based computed
      tomographic isocontour method was developed to identify intestinal anatomic
      regions, and FDG uptake was integrated over these regions to achieve reproducible
      quantification during longitudinal assessment of individual mice. Intestinal FDG
      uptake was compared with histologic scores and with glucose transporter 1 levels
      in mucosal immune cells by flow cytometry. RESULTS: Intestinal FDG uptake
      quantitatively correlated with disease activity in mild (C3H/HeJ.IL-10(-/-)) and
      severe (129.Galphai2(-/-), CD4(+) CD45RB(high), and Galphai2(-/-) CD3(+)
      transfer) murine colitis models at all time points examined (P < .05) and was
      sufficiently sensitive to detect preclinical inflammation. FDG uptake was
      correlated by flow cytometric detection of glucose transporter 1 levels in
      mucosal CD4(+) T lymphocyte but not other intestinal immune cell types. CD4(+) T
      cell transfer in vivo confirmed that mucosal FDG uptake was associated with the
      activated but not quiescent state. When intestinal inflammation was increased by
      treatment with piroxicam and decreased with anti-TL1A treatment, FDG uptake was
      correspondingly altered. CONCLUSIONS: This study clarifies the cellular basis of
      FDG signal in intestinal inflammation and introduces computed tomographic
      isocontour analysis of FDG-PET imaging for standardized quantitation of immune
      colitis.

PMID- 18639554
TI  - Temporary feeding inhibition caused by artificial abdominal distension in the
      bedbug, Cimex lectularius.
AB  - Abdominal distension of haematophagous insects caused by ingested blood has been
      recognised as an important contributor to triggering meal termination, feeding
      inhibition and further susceptibility to host signals. Factors that regulate
      feeding behaviour of the common bedbug, Cimex lectularius, are poorly understood.
      By injecting air directly into the body cavity of virgin female C. lectularius we
      artificially induced abdominal distension without providing chemical cues of the
      blood meal and without applying gut distension. Body length increased to 138%
      after feeding and 147% after inflation. The early decline in body volume is
      similar in blood-fed bugs but after between 8 and 24h became faster in inflated
      than fed bedbugs. Artificially inflated individuals remained feeding-inhibited at
      lower abdominal distensions than those that terminate blood ingestion (to ca.
      135% initial body length, or up to about 5h). Feeding activity resumed earlier in
      inflated than blood-fed bugs. These results suggest that artificial abdominal
      distension has an inhibitory effect on feeding but is not the sole mechanism in
      preventing further feeding.

PMID- 18639555
TI  - Role of activated CaMKII in abnormal calcium homeostasis and I(Na) remodeling
      after myocardial infarction: insights from mathematical modeling.
AB  - Ca(2+)/calmodulin-dependent protein kinase II is a multifunctional
      serine/threonine kinase with diverse cardiac roles including regulation of
      excitation contraction, transcription, and apoptosis. Dynamic regulation of
      CaMKII activity occurs in cardiac disease and is linked to specific disease
      phenotypes through its effects on ion channels, transporters, transcription and
      cell death pathways. Recent mathematical models of the cardiomyocyte have
      incorporated limited elements of CaMKII signaling to advance our understanding of
      how CaMKII regulates cardiac contractility and excitability. Given the importance
      of CaMKII in cardiac disease, it is imperative that computer models evolve to
      capture the dynamic range of CaMKII activity. In this study, using mathematical
      modeling combined with biochemical and imaging techniques, we test the hypothesis
      that CaMKII signaling in the canine infarct border zone (BZ) contributes to
      impaired calcium homeostasis and electrical remodeling. We report that the level
      of CaMKII autophosphorylation is significantly increased in the BZ region.
      Computer simulations using an updated mathematical model of CaMKII signaling
      reproduce abnormal Ca(2+) transients and action potentials characteristic of the
      BZ. Our simulations show that CaMKII hyperactivity contributes to abnormal Ca(2+)
      homeostasis and reduced action potential upstroke velocity due to effects on
      I(Na) gating kinetics. In conclusion, we present a new mathematical tool for
      studying effects of CaMKII signaling on cardiac excitability and contractility
      over a dynamic range of kinase activities. Our experimental and theoretical
      findings establish abnormal CaMKII signaling as an important component of
      remodeling in the canine BZ.

PMID- 18639556
TI  - Transient activation of p38 MAP kinase and up-regulation of Pim-1 kinase in
      cardiac hypertrophy despite no activation of AMPK.
AB  - AMP-activated protein kinase (AMPK), is an important regulator of cardiac
      metabolism, but its role is not clearly understood in pressure overload induced
      hypertrophy. In addition, the relationship between AMPK and other important
      protein kinases such as p38 MAP kinase, Akt and Pim-1 is unclear. Thus we studied
      the time course of AMPK activity and phosphorylation of Thr-172 of its alpha
      subunit during the development of cardiac hypertrophy. In parallel, we examined
      the expression and activation of key kinases known to be involved in cardiac
      hypertrophy that could interact with AMPK (i.e. p38 MAP kinase, Akt and Pim-1).
      Male C57BL/6J mice underwent sham or transverse aortic constriction (TAC) surgery
      and the hearts were harvested 2, 4, 6 and 8 weeks later. Despite significant left
      ventricular (LV) hypertrophy, LV dilation and impaired LV contractile function at
      all time points in TAC compared to sham mice, the activity and phosphorylation of
      AMPK were similar to sham. In contrast, p38 and Pim-1 protein expression was
      transiently increased in TAC mice at 2 and 4 weeks and at 2, 4 and 6 weeks,
      respectively. In addition, p38 activation by phosphorylation was also transiently
      increased at 2 to 6 weeks. There were no differences between sham and TAC mice in
      p38, Akt or Pim-1 at 8 weeks. In conclusion, TAC resulted in a transient up
      regulation in the expression of p38 and Pim-1 despite no activation of AMPK or
      Akt.

PMID- 18639557
TI  - Effect of altering neural, muscular and tendinous factors associated with aging
      on balance recovery using the ankle strategy: a simulation study.
AB  - Aging is associated with declines in neuromuscular function and reduced ability
      to recover balance from an imbalance episode. However, little is known about the
      relations amongst these factors. The purpose of this study was to determine the
      relative influence of age-related changes in neural, muscular and tendinous
      properties on the ability to recovery balance from a forward leaning position
      using the ankle strategy. A computer simulation was developed which consisted of
      an inverted pendulum with one rotational degree of freedom controlled by two
      muscles representing the ankle joint plantar flexor (PF) and dorsi flexor (DF)
      muscle groups. Model parameter values were adjusted so that the isometric torque
      angle relation was in agreement with experimental ankle joint torque-angle curves
      from the literature. Muscle excitation was adjusted to match an experimentally
      determined maximum recoverable lean angle (MRLA) of 7.2 degrees (baseline
      condition). The effect of 20% alterations to maximum isometric force, optimum
      muscle fibre length, maximum shortening velocity, tendon stiffness, reaction time
      delay (RTD), activation time constant and the maximum excitation of the PF
      muscles, and maximum excitation of the DF muscles (co-activation) on MRLA was
      then assessed. The parameters that had the greatest influence on MRLA were
      maximum isometric force, the maximum excitation of the ankle joint PFs and RTD,
      which, respectively, resulted in 19.0%, 17.8% and 4.6% reductions in MRLA.
      Individual changes to other parameters influenced MRLA by less than 1.9%. When
      selected parameter values were adjusted in accordance with age-related changes
      reported in the literature, MRLA was reduced to 5.3 degrees , a value in relative
      agreement with experimental values reported in the literature (4.6+/-1.8 degrees
      ). In general, these results suggest that MRLA is most sensitive to PF muscle
      mass and the ability to maximally activate the PFs, and that the combined effect
      of multiple changes in neural, muscular and tendinous parameters reported to
      occur with aging can have a profound effect on the ability to recover balance
      from a forward fall using the ankle strategy.

PMID- 18639558
TI  - Increased Ca(2+) sparks and sarcoplasmic reticulum Ca(2+) stores potentially
      determine the spontaneous activity of pulmonary vein cardiomyocytes.
AB  - Pulmonary veins (PVs) contain cardiomyocytes with spontaneous activity that may
      be responsible for PV arrhythmia. Abnormal Ca(2+) regulation is known to
      contribute to PV arrhythmogenesis. The purpose of this study was to investigate
      whether PV cardiomyocytes with spontaneous activity have different intracellular
      Ca(2+) ([Ca(2+)](i)) transients, Ca(2+) sparks and responses to isoproterenol and
      ryanodine receptor modulators (magnesium and FK506) than do PV cardiomyocytes
      without spontaneous activity and left atrial (LA) cardiomyocytes. Through
      fluorescence and confocal microscopy, we evaluated the [Ca(2+)](i) transients and
      Ca(2+) sparks in isolated rabbit PV and LA cardiomyocytes. PV cardiomyocytes with
      spontaneous activity had larger [Ca(2+)](i) transients and sarcoplasmic reticulum
      (SR) Ca(2+) stores than PV cardiomyocytes without spontaneous activity or LA
      cardiomyocytes. PV cardiomyocytes with spontaneous activity also had a higher
      incidence and frequency of Ca(2+) sparks, and had Ca(2+) sparks with larger
      amplitudes than other cardiomyocytes. Magnesium (5.4 mM) reduced the [Ca(2+)](i)
      transient amplitude and beating rate in PV cardiomyocytes with spontaneous
      activity. However, in contrast with other cardiomyocytes, low doses (1.8 mM) of
      magnesium did not reduce the [Ca(2+)](i) transients amplitude in PV
      cardiomyocytes with spontaneous activity. FK506 (1 microM) diminished the SR
      Ca(2+) stores in PV cardiomyocytes with spontaneous activity to a lesser extent
      than that in other cardiomyocytes. Isoproterenol (10 nM) increased the
      [Ca(2+)](i) transient amplitude to a lesser extent in LA cardiomyocytes than in
      PV cardiomyocytes with or without spontaneous activity. In conclusion, our
      results suggest that enhanced [Ca(2+)](i) transients, increased Ca(2+) sparks and
      SR Ca(2+) stores may contribute to the spontaneous activity of PV cardiomyocytes.

PMID- 18639559
TI  - Resveratrol reduces infarct size and improves ventricular function after
      myocardial ischemia in rats.
AB  - The purpose of this study was to investigate the effect of resveratrol, a
      polyphenol present in grapes and red wine, on ventricular remodeling after
      myocardial infarction (MI) in rats. After permanent ligation of the left anterior
      descending artery, surviving rats were randomly allocated to three groups and
      treated with 1 mg/kg/day resveratrol (R-1 group), 0.1 mg/kg/day resveratrol (R
      0.1 group), or vehicles (control group) administered by intraperitoneal injection
      once daily for four weeks. We examined the effects of resveratrol by
      echocardiography, hemodynamic studies, histologic examinations, and real-time
      quantitative polymerase chain reaction. The R-1 group had significantly increased
      fractional shortening of the left ventricle, ameliorated left ventricular
      dilatation, reduced left ventricular end-diastolic pressure, and reduced infarct
      size. In contrast, the R-0.1 group experienced no beneficial effects on
      myocardial infarction. The R-1 group also had significantly attenuated expression
      of myocardial atrial natriuretic peptide and transforming growth factor-beta1
      mRNAs. This study indicates that resveratrol is a potent cardioprotective agent
      in MI rats. Its cardioprotective effects may be due to a reduction of atrial
      natriuretic peptide and transforming growth factor-beta1, which are known to
      protect the heart from detrimental remodeling.

PMID- 18639560
TI  - Effects of human Werner helicase on intrachromosomal homologous recombination
      mediated DNA deletions in mice.
AB  - Werner syndrome (WS) is a rare genetic disorder characterized by accelerated
      aging and aging-related diseases including cancer. WS is caused by autosomal
      recessive mutations in the WRN gene, which is involved in genome maintenance
      although precise functions of WRN are not well understood. To further investigate
      the role of WRN, we used transgenic mice over-expressing a human helicase mutant
      WRN gene (hMW). We determined homologous recombination (HR) events leading to 70
      kb deletions in the p(un) locus visualized as pigmented cells in the retinal
      pigment epithelium. hMW mice had an increased spontaneous frequency of DNA
      deletions compared to control mice, consistent with WRN involvement in HR
      suppression. In addition, 4-nitroquinoline 1-oxide (4-NQO), which can cause both
      oxidative stress and DNA adduct formation, significantly increased the frequency
      of DNA deletions in both control and hMW mice. In order to assess how oxidative
      stress may modulate this phenotype, we treated mice with the glutathione (GSH)
      synthesis inhibitor, buthionine sulfoximine (BSO). The frequency of DNA deletions
      increased significantly in control mice, but not in hMW littermates. To elucidate
      the cause of this discrepancy, we determined total GSH levels as a measure of
      anti-oxidative defense. BSO significantly decreased GSH levels in both hMW mice
      and control mice, while 4-NQO increased GSH levels in all mice. These findings
      suggest that the reduction of GSH by BSO or compensatory increase of GSH by 4-NQO
      had little impact on hMW mice in which HR repair is compromised. Therefore,
      oxidative stress impacts HR repair in hMW mice less than control mice and effects
      of the mutated gene may be exacerbated by direct DNA damage from 4-NQO. This
      mouse model of WS in conjunction with different DNA damaging agents may provide
      insight into mechanisms of genomic instability, DNA repair, and carcinogenesis.

PMID- 18639562
TI  - Inhibition of glial inflammatory activation and neurotoxicity by tricyclic
      antidepressants.
AB  - Glial activation and neuroinflammatory processes play an important role in the
      pathogenesis of neurodegenerative diseases such as Alzheimer's disease,
      Parkinson's disease, and HIV dementia. Activated glial cells can secrete various
      proinflammatory cytokines and neurotoxic mediators, which may contribute to
      neuronal cell death. Inhibition of glial activation may alleviate
      neurodegeneration under these conditions. In the present study, the
      antiinflammatory and neuroprotective effects of tricyclic antidepressants were
      investigated using cultured brain cells as a model. The results showed that
      clomipramine and imipramine significantly decreased the production of nitric
      oxide or tumor necrosis factor-alpha (TNF-alpha) in microglia and astrocyte
      cultures. Clomipramine and imipramine also attenuated the expression of inducible
      nitric oxide synthase and proinflammatory cytokines such as interleukin-1beta and
      TNF-alpha at mRNA levels. In addition, clomipramine and imipramine inhibited
      IkappaB degradation, nuclear translocation of the p65 subunit of NF-kappaB, and
      phosphorylation of p38 mitogen-activated protein kinase in the lipopolysaccharide
      stimulated microglia cells. Moreover, clomipramine and imipramine were
      neuroprotective as the drugs reduced microglia-mediated neuroblastoma cell death
      in a microglia/neuron co-culture. Therefore, these results imply that
      clomipramine and imipramine have antiinflammatory and neuroprotective effects in
      the central nervous system by modulating glial activation.

PMID- 18639561
TI  - Mechanisms of peroxisome proliferator-induced DNA hypomethylation in rat liver.
AB  - Genomic hypomethylation is a consistent finding in both human and animal tumors
      and mounting experimental evidence suggests a key role for epigenetic events in
      tumorigenesis. Furthermore, it has been suggested that early changes in DNA
      methylation and histone modifications may serve as sensitive predictive markers
      in animal testing for carcinogenic potency of environmental agents. Alterations
      in metabolism of methyl donors, disturbances in activity and/or expression of DNA
      methyltransferases, and presence of DNA single-strand breaks could contribute to
      the loss of cytosine methylation during carcinogenesis; however, the precise
      mechanisms of genomic hypomethylation induced by chemical carcinogens remain
      largely unknown. This study examined the mechanism of DNA hypomethylation during
      hepatocarcinogenesis induced by peroxisome proliferators WY-14,643 (4-chloro-6
      (2,3-xylidino)-pyrimidynylthioacetic acid) and DEHP (di-(2-ethylhexyl)phthalate),
      agents acting through non-genotoxic mode of action. In the liver of male Fisher
      344 rats exposed to WY-14,643 (0.1% (w/w), 5 months), the level of genomic
      hypomethylation increased by approximately 2-fold, as compared to age-matched
      controls, while in the DEHP group (1.2% (w/w), 5 months) DNA methylation did not
      change. Global DNA hypomethylation in livers from WY-14,643 group was accompanied
      by the accumulation of DNA single-strand breaks, increased cell proliferation,
      and diminished expression of DNA methyltransferase 1, while the metabolism of
      methyl donors was not affected. In contrast, none of these parameters changed
      significantly in rats fed DEHP. Since WY-14,643 is much more potent carcinogen
      than DEHP, we conclude that the extent of loss of DNA methylation may be related
      to the carcinogenic potential of the chemical agent, and that accumulation of DNA
      single-strand breaks coupled to the increase in cell proliferation and altered
      DNA methyltransferase expression may explain genomic hypomethylation during
      peroxisome proliferator-induced carcinogenesis.

PMID- 18639564
TI  - Transcriptional regulation at a HTR1A polymorphism associated with mental
      illness.
AB  - The serotonin-1A (5-HT1A) receptor serves as a hub to regulate the activity and
      actions of the serotonin system, and is expressed both as a presynaptic
      autoreceptor on raphe neurons, and as a major postsynaptic receptor in
      hippocampal, cortical, and hypothalamic regions involved in mood, emotion and
      stress response. As such, the level of expression of 5-HT1A receptors is
      implicated in the development of anxiety and depression phenotypes. This review
      focuses on the C(-1019)G (rs6295) promoter polymorphism of the 5-HT1A receptor
      gene (HTR1A) and its effect on the activity of transcription factors that
      recognize the C-allele, including Deaf-1, Hes1 and Hes5; its effects on 5-HT1A
      receptor expression in pre- and postsynaptic areas; as well as its implication in
      early postnatal development and adult neurogenesis in the hippocampus and cortex.
      Although several studies have now replicated the association of the G-allele with
      depression, panic disorder, neuroticism, and reduced response to antidepressant
      or antipsychotic treatment, ethnic, disease and genetic heterogeneity among
      subjects in different studies may obscure such associations. Gene-gene
      interaction studies suggest that the 5-HT1A receptor G(-1019) allele is a risk
      allele which could be used as a marker for depression and related mood disorders.
      Finally, association of the G(-1019) allele with increased raphe 5-HT1A binding
      potential, increased amygdala reactivity to emotional stimuli, and reduced
      amygdala volume, particularly in disease states, suggests a functional role for
      the C(-1019)G site in 5-HT1A receptor dys-regulation and predisposition to mental
      illness.

PMID- 18639563
TI  - Roles of ectodomain and transmembrane regions in ethanol and agonist action in
      purinergic P2X2 and P2X3 receptors.
AB  - The present work investigated sites of ethanol action in ATP-gated P2X receptors
      (P2XRs) using chimeric strategies that exploited the differences in ethanol
      response between P2X2R (inhibition) and P2X3R (potentiation). We tested ethanol
      (10-200mM) effects on ATP- and alpha,beta-methylene-ATP (alpha,beta-meATP)
      induced currents in wildtype P2X2, P2X3 and chimeric P2X2/P2X3Rs expressed in
      Xenopus oocytes using two-electrode voltage-clamp (-70mV). Exchanging ectodomain
      regions of P2X2 and P2X3Rs reversed wildtype ethanol responses. Substituting back
      portions of the P2X2R ectodomain at TM interfaces in chimeras that contained the
      P2X3R ectodomain restored wildtype P2X2R-like ethanol response. Point mutations
      that replaced non-conserved ectodomain residues at TM interfaces of P2X3Rs with
      homologous P2X2R residues identified positions that reversed the direction (304)
      or changed the magnitude (53, 55 and 313) of ethanol response. Homologous
      substitutions in P2X2Rs did not significantly alter wildtype P2X2R-like ethanol
      responses. These findings suggest that ectodomain segments at TM interfaces play
      key roles in determining qualitative and quantitative responses to ethanol of
      P2X2 and P2X3Rs. Studies that substituted TM regions of P2X3R with respective
      P2X2R TMs indicate that the TM1, but not the TM2, region plays a role in
      determining the magnitude of ethanol response. Studies with ATP and alpha,beta
      meATP support prior indications that TM regions are important in agonist
      desensitization and suggest that both ectodomain and TM regions play roles in
      determining agonist potency and selectivity. Overall, these findings are the
      first to identify potential targets for ethanol in P2X2 and P2X3Rs and should
      provide insight into the sites of ethanol action in other P2XRs.

PMID- 18639565
TI  - Linking performance with brain potentials: mental rotation-related negativity
      revisited.
AB  - It has been suggested that the amplitude of parietal event-related potentials
      (ERPs) provides a neural signature of imaginary object rotation. Here, we
      evaluated the relationship between the so-called rotation-related negativity and
      individual performance in the mental rotation of alphanumeric characters. The
      signals were averaged with respect to two time events, stimulus onset
      (ERP(ONSET)) and response time (ERP(RT)) indexing, respectively, an early and a
      late phase of the mental rotation. The amplitude of a slow parietal negativity
      varied with the rotation angle in both ERP(ONSET) and ERP(RT). The amplitude of
      this potential correlated negatively with task performance, indexed by response
      time. This was the case in ERP(RT) but not in ERP(ONSET). We further show that
      variations of the ERP(ONSET) amplitude with the rotation angle might at least
      partially result from increased duration/latency jitter among single trials.
      These results suggest that late rather than early processing supports task
      solution in mental rotation.

PMID- 18639566
TI  - The asymmetry of the fusiform face area is a stable individual characteristic
      that underlies the left-visual-field superiority for faces.
AB  - Recognition of faces is better when faces are presented in the left than right
      visual-field. Furthermore, this perceptual asymmetry is a stable individual
      characteristic. Although it has been commonly assumed that the right hemispheric
      dominance for face processing underlies this left-visual-field superiority in
      face recognition, this neural-behavioral association has never been directly
      demonstrated. Here we applied functional MRI (fMRI) to measure the magnitude of
      the asymmetric response to faces for each subject. To determine whether the
      asymmetric neural response to faces is stable across sessions, subjects returned
      for a second fMRI session. In addition, subjects performed a behavioral
      experiment outside the scanner where they had to recognize centrally presented
      chimeric faces, which presented different identities in the right- and left
      visual-field. This task yielded a measure of the magnitude of the left-visual
      field bias for each subject. Our findings show that the magnitude of the
      asymmetry of the face-selective area in the fusiform gyrus (FFA) is highly
      consistent for each individual across scans. We then show that the behavioral
      left-visual-field asymmetry, measured outside the scanner, was strongly and
      specifically correlated with the asymmetry of the FFA across subjects, but not
      with other face-specific or nearby object-general regions. Our findings provide
      the first empirical evidence for the prevalent idea that perceptual asymmetries
      in face recognition are associated with the well-known hemispheric asymmetry for
      faces. We conclude that the FFA asymmetry is a highly stable individual
      characteristic that underlies the well-established left-visual-field superiority
      for face recognition.

PMID- 18639568
TI  - The role of accurate testosterone testing in the treatment and management of male
      hypogonadism.
AB  - A reduced concentration of serum testosterone resulting in male hypogonadism is a
      well described endocrine abnormality associated with classical signs and
      symptoms. This manuscript presents one such patient. However, low serum
      testosterone is being recognized more commonly associated with aging and chronic
      disease. It is in this situation in which the signs and symptoms of male
      hypogonadism can be subtle and non-specific. This manuscript reviews examples of
      such situations and highlights our need to have a reliable and accurate measure
      of serum testosterone. Both clinicians and researchers need better assays to
      better understand basic mechanisms, diagnose, treat, and monitor men with
      testosterone deficiency.

PMID- 18639567
TI  - Preferences of 14 rat strains for 17 taste compounds.
AB  - Two-bottle choice tests were used to assess the taste preferences of 8 male and 8
      female rats from 3 outbred strains (SD, LE, WI) and 11 inbred strains (BN, BUF,
      COP, DA, Dahl-S, F344, FHH, LEW, Noble, PVG, SHR). Each rat received a series of
      109 48-h tests with a choice between water and a "taste solution". Four to eight
      concentrations of the following compounds were tested: NaCl, CaCl2, NH4Cl, KCl,
      MgCl2, saccharin, sucrose, ethanol, HCl, citric acid, quinine hydrochloride
      (QHCl), caffeine, denatonium, monosodium glutamate (MSG), Polycose, corn oil, and
      capsaicin. Strain differences (p<0.001) were observed in preferences for at least
      one concentration of all compounds tested except denatonium (p=0.0015). There
      were also strain differences in the following ancillary measures: fungiform
      papillae number, water intake, food intake, and body weight. There were sex
      differences in food intake and body weight but no concerted sex differences in
      any of the other measures, including preferences for any taste solution. This
      comprehensive source of information can be used to guide the choice of
      appropriate rat strains and taste solution concentrations for future genetic
      studies.

PMID- 18639569
TI  - Gene expression profiles modulated by the human carcinogen aristolochic acid I in
      human cancer cells and their dependence on TP53.
AB  - Aristolochic acid (AA) is the causative agent of urothelial tumours associated
      with aristolochic acid nephropathy. These tumours contain TP53 mutations and over
      express TP53. We compared transcriptional and translational responses of two
      isogenic HCT116 cell lines, one expressing TP53 (p53-WT) and the other with this
      gene knocked out (p53-null), to treatment with aristolochic acid I (AAI) (50-100
      microM) for 6-48 h. Modulation of 118 genes was observed in p53-WT cells and 123
      genes in p53-null cells. Some genes, including INSIG1, EGR1, CAV1, LCN2 and
      CCNG1, were differentially expressed in the two cell lines. CDKN1A was
      selectively up-regulated in p53-WT cells, leading to accumulation of TP53 and
      CDKN1A. Apoptotic signalling, measured by caspase-3 and -7 activity, was TP53
      dependent. Both cell types accumulated in S phase, suggesting that AAI-DNA
      adducts interfere with DNA replication, independently of TP53 status. The
      oncogene MYC, frequently over-expressed in urothelial tumours, was up-regulated
      by AAI, whereas FOS was down-regulated. Observed modulation of genes involved in
      endocytosis, e.g. RAB5A, may be relevant to the known inhibition of receptor
      mediated endocytosis, an early sign of AA-mediated proximal tubule injury. AAI
      DNA adduct formation was significantly greater in p53-WT cells than in p53-null
      cells. Collectively, phenotypic anchoring of the AAI-induced expression profiles
      to DNA adduct formation, cell-cycle parameters, TP53 expression and apoptosis
      identified several genes linked to these biological outcomes, some of which are
      TP53-dependent. These results strengthen the importance of TP53 in AA-induced
      cancer, and indicate that other alterations, e.g. to MYC oncogenic pathways, may
      also contribute.

PMID- 18639570
TI  - The in vivo rat muscle force model is a reliable and clinically relevant test of
      consistency among botulinum toxin preparations.
AB  - To ensure safety and predictable clinical efficacy, the biological activity of
      type A botulinum toxin (BoNT-A) preparations must remain consistent. Several
      methods have been employed to assess consistency but lack clinical applicability
      and/or are associated with animal welfare concerns. Here, we describe a novel in
      vivo rat muscle force model for evaluating the biological activity of formulated
      BoNT-A product (Dysport) prepared from bulk toxin batches manufactured at
      different facilities. Toxin activity was assessed by measuring muscle force
      generation over time in the triceps surae muscles in the rat hind leg. Animals
      received 0.1 ml gelatine phosphate buffer (negative vehicle control) or 0.1 or
      1.0 LD50 units of BoNT-A in phosphate buffer. Batch equivalence and consistency
      were confirmed by the lack of significant differences in muscle force generation
      and duration of effect between each test batch and the reference preparation
      tested in the same series of experiments. The reduction in muscle force
      generation was dose-related and reproducible for all active treatment groups. At
      appropriate dose levels, the rat muscle force model is a reliable tool for
      measuring biological activity in bulk toxin batches used to formulate clinical
      product and demonstrates the consistency of batches manufactured over many years.

PMID- 18639571
TI  - The effects of longitudinal chromatic aberration and a shift in the peak of the
      middle-wavelength sensitive cone fundamental on cone contrast.
AB  - Longitudinal chromatic aberration is a well-known imperfection of visual optics,
      but the consequences in natural conditions, and for the evolution of receptor
      spectral sensitivities are less well understood. This paper examines how
      chromatic aberration affects image quality in the middle-wavelength sensitive (M
      ) cones, viewing broad-band spectra, over a range of spatial frequencies and
      focal planes. We also model the effects on M-cone contrast of moving the M-cone
      fundamental relative to the long- and middle-wavelength (L- and M-cone)
      fundamentals, while the eye is accommodated at different focal planes or at a
      focal plane that maximizes luminance contrast. When the focal plane shifts
      towards longer (650 nm) or shorter wavelengths (420 nm) the effects on M-cone
      contrast are large: longitudinal chromatic aberration causes total loss of M-cone
      contrast above 10-20 c/d. In comparison, the shift of the M-cone fundamental
      causes smaller effects on M-cone contrast. At 10 c/d a shift in the peak of the M
      cone spectrum from 560 to 460 nm decreases M-cone contrast by 30%, while a 10 nm
      blue-shift causes only a minor loss of contrast. However, a noticeable loss of
      contrast may be seen if the eye is focused at focal planes other than that which
      maximizes luminance contrast. The presence of separate long- and middle
      wavelength sensitive cones therefore has a small, but not insignificant cost to
      the retinal image via longitudinal chromatic aberration. This aberration may
      therefore be a factor limiting evolution of visual pigments and trichromatic
      color vision.

PMID- 18639572
TI  - Aberrations of emmetropic subjects at different ages.
AB  - We made on-axis aberrations and horizontal peripheral refraction measurements of
      emmetropic subjects (spherical equivalent -0.88D to +0.75D) aged between 19 and
      70 years. We found smaller changes in on-axis aberrations with age than has
      previously been reported, possibly because of the small refractive error range of
      our subject group. Higher order root-mean-squared aberrations increased by 26%
      across the age range (5 mm pupils), with significant age related changes in 4th-
      and 6th-order aberrations. The only aberration co-efficient to change
      significantly was horizontal coma co-efficient C(3, 1). Several aberration co
      efficients were significantly different from zero across the group of subjects.
      The only changes in peripheral refraction with increase in age were shifts in the
      turning points of the spherical equivalent and horizontal/vertical astigmatism
      towards less temporal visual field angles.

PMID- 18639573
TI  - Endogenous attention and illusory line motion depend on task set.
AB  - Task set has been shown to determine some important cognitive operations like
      conscious perception [Rafal, R. D., Ward, R., & Danziger, S. (2006). Selection
      for action and selection for awareness: Evidence from hemispatial neglect. Brain
      Research, 1080(1), 2-8], and the exogenous orienting of spatial attention [Folk,
      C. L., Remington, R. W., & Johnston, J. C. (1992). Involuntary covert orienting
      is contingent on attentional control settings. Journal of Experimental
      Psychology: Human Perception and Performance, 18(4), 1030-1044; Lupianez, J.,
      Ruz, M., Funes, M. J., & Milliken, B. (2007). The manifestation of attentional
      capture: Facilitation or IOR depending on task demands. Psychological Research,
      71(1), 77-91]. In the present study we investigate whether endogenous attention
      would also be task-dependent. We use an illusion of movement, the illusory line
      motion [Hikosaka, O., Miyauchi, S., & Shimojo, S. (1993). Focal visual attention
      produces illusory temporal order and motion sensation. Vision Research, 33(9),
      1219-1240] to explore this question. Our results revealed that endogenously
      attending to detect the appearance of a target produce different consequences in
      modulating the illusion of movement than endogenously attending to discriminate
      one of its features. We suggest that endogenous attention is implemented
      differently depending on the task at hand, producing different effects on
      perceptual integration.

PMID- 18639574
TI  - Visual search for a target against a 1/f(beta) continuous textured background.
AB  - We present synthetic surface textures as a novel class of stimuli for use in
      visual search experiments. Surface textures have certain advantages over both the
      arrays of abstract discrete items commonly used in search studies and photographs
      of natural scenes. In this study we investigate how changing the properties of
      the surface and target influence the difficulty of a search task. We present a
      comparison with Itti and Koch's saliency model and find that it fails to model
      human behaviour on these surfaces. In particular it does not respond to changes
      in orientation in the same manner as human observers.

PMID- 18639576
TI  - Effects of intrahippocampal cannabinoid receptor agonist and antagonist on radial
      maze and T-maze delayed alternation performance in rats.
AB  - Brain cannabinoid receptors are abundantly distributed in the hippocampus,
      however their detailed role in learning and memory remains unclear. This study
      investigated the role of hippocampal cannabinoid receptors for performing two
      kinds of working memory tasks. In experiment 1, intrahippocampal infusion of
      cannabinoid receptor agonist WIN 55,212-2 (1-2 microg/side) dose-dependently
      disturbed radial maze performance in rats. In experiment 2, WIN 55,212-2 (2
      microg/side) disturbed the performance of delayed alternation in a T-maze by
      increasing the errors and successive errors, and on the other hand, a cannabinoid
      receptor antagonist AM 281 (1 microg/side) did not have any significant effects.
      Disruptive effect of WIN 55,212-2 on the number of errors in delayed alternation
      was blocked by the pretreatment with intraperitoneal AM 281 (2 mg/kg). Results
      suggest that hippocampal cannabinoid receptors are involved in the performance of
      working memory tasks. A possible role of endogenous cannabinoid system in the
      hippocampus was discussed in terms of an inhibitory adjustment of behavior based
      on the outcome of animals' previous response.

PMID- 18639575
TI  - Antagonistic pleiotropy and p53.
AB  - George Williams' antagonistic pleiotropy theory of aging proposes that cellular
      damage and organismal aging are caused by pleiotrophic genes, or genes with
      multiple phenotypic effects [Williams, G.C., 1957. Pleiotropy, natural selection,
      and the evolution of senescence. Evolution 11, 398-411]. According to this
      theory, genes that exhibit antagonistic pleiotropy increase the odds of
      successful reproduction early in life, but have deleterious effects later in
      life. The tumor suppressor p53 confers protection against cancer (and death) by
      interrupting the abnormal proliferation of cells. When control of proliferation
      is applied to normal stem cells, however, it can impair tissue homeostasis and
      accelerate aging. We use data from recently developed models of accelerated aging
      in mice to determine if the deleterious effects of p53 on aging reflect
      antagonistic pleiotropy of the p53 gene or are attributable to genes that can
      modify p53 activity but are evolving independently.

PMID- 18639577
TI  - Ketamine induces hyperactivity in rats and hypersensitivity to nicotine in rat
      striatal slices.
AB  - The symptoms of schizophrenia can be modeled in rats through blockade of
      ionotropic glutamate receptors, which induces changes in central dopamine
      circuits. These circuits also contain nicotinic acetylcholine receptors that are
      activated by nicotine. A role for nicotine in the etiology of schizophrenia is
      supported by clinical observations of high tobacco use rates in individuals
      experiencing the psychopathology. The present study investigated the effect of
      the ionotropic glutamate receptor antagonist ketamine on the function of striatal
      nicotinic acetylcholine receptors to understand better the potential role of
      these receptors in schizophrenia. Ketamine (0.1-300 microM) was ineffective to
      evoke [3H] overflow from rat striatal slices preloaded with [3H]dopamine.
      Application of psychotomimetic ketamine concentrations (1-10 microM) to striatal
      slices augmented nicotine-evoked [3H] overflow. Finally, rats received ketamine
      (30-50 mg/kg) injections for 30 days, to model the development of the disorder,
      and hyperactivity was observed, although repeated ketamine treatment did not
      significantly alter nicotine-evoked [3H]dopamine overflow. These data indicate
      that the function of nicotinic acetylcholine receptors that mediate dopamine
      release are altered by ketamine, and support a role for nicotinic acetylcholine
      receptors in schizophrenia pathology.

PMID- 18639578
TI  - An adjusting-dose procedure for assessing the reinforcing effects of nitrous
      oxide with humans.
AB  - Despite continued abuse, there is a paucity of empirical investigations on
      inhalants as reinforcers. The present study attempted to derive a method for
      studying the reinforcing effects of nitrous oxide (N2O) with human participants.
      An adjusting-dose procedure was employed to assess choice allocation for
      inhalation periods of varying doses of N2O. After experiencing the experimental
      parameters in forced-choice trials, participants made choices between a fixed
      dose of 0% N2O (i.e., 100% O2) and an adjusting dose of N2O (0-50% N2O in O2).
      The adjusting dose titrated as a function of the participant's choices.
      Conditions were run to stability and systematically replicated within-subject.
      Stable choice allocation served as both the chief dependent variable and an
      indication of the optimal reinforcing dose of N2O for that participant.
      Consistent with previous research on N2O, there was between-subject variability
      in the reinforcing effects of N2O; however, stable within-subject choice
      allocation was observed for 6 out of 8 participants. This method of assessing
      drug choice in humans allows for the testing of multiple doses within-subject,
      which is imperative, given that the reinforcing effects of drugs are known to
      vary across subjects and as a function of dose.

PMID- 18639579
TI  - Genetic and early environmental contributions to alcohol's aversive and
      physiological effects.
AB  - Genetic and early environmental factors interact to influence ethanol's
      motivational effects. To explore these issues, a reciprocal cross-fostering
      paradigm was applied to Fischer and Lewis rats. The adult female offspring
      received vehicle or the kappa opioid antagonist nor-BNI (1 mg/kg) followed by
      assessments of conditioned taste aversion (CTA), blood alcohol concentrations
      (BACs) and hypothermia induced by 1.25 g/kg intraperitoneal ethanol. CTA
      acquisition in the in-fostered Fischer and Lewis animals did not differ; however,
      the Fischer maternal environment produced stronger acquisition in the cross
      fostered Lewis rats versus their in-fostered counterparts. CTAs in the Fischer
      rats were not affected by cross-fostering. In extinction, the in-fostered Lewis
      animals displayed stronger aversions than the Fischer groups on two trials (of
      12) whereas the cross-fostered Lewis differed from the Fischer groups on nine
      trials. Despite these CTA effects, Lewis rats exhibited higher BACs and stronger
      hypothermic responses than Fischer with no cross-fostering effects in either
      strain. No phenotypes were affected by nor-BNI. These data extend previous
      findings dissociating the aversive and peripheral physiological effects of
      ethanol in female Fischer and Lewis rats, and highlight the importance of genetic
      and early environmental factors in shaping subsequent responses to alcohol's
      motivational effects in adulthood.

PMID- 18639580
TI  - The differential effects of acetaminophen on lipopolysaccharide induced
      hyperalgesia in various mouse pain models.
AB  - We investigated effects of acetaminophen on LPS-induced hyperalgesia in various
      pain models. We examined the changes of pain behaviors induced by formalin
      injected subcutaneously (s.c.) in the hind paw, with substance P (SP) and
      glutamate injected inthrathecally (i.t.). Hyperalgesia was induced by LPS
      intraperitoneal injection 1 day prior to the pain test. LPS-induced hyperalgesia
      was exhibited in nociceptive behaviors induced by formalin s.c. (only in the
      second phase), SP and glutamate i.t. injection. APAP showed a dose-dependent
      antinociceptive effect on the saline- and LPS-pretreated group in the formalin
      and SP pain model. However, the analgesic effect of APAP was not observed in the
      glutamate pain model. To clarify the action site, APAP was administered i.t. or
      intracerebroventricularly (i.c.v.) 30 min prior to behavioral tests. The 2nd
      phase of formalin response was not only increased by LPS, but it also
      significantly attenuated by i.c.v. injections of APAP. However, the effect of
      APAP was observed only in the LPS-pretreatment, but not in the control group.
      These results suggest that LPS-induced hyperalgesia in the formalin 2nd phase may
      be involved in the SP-sensitive neuronal pathways, in which the hyperalgesic
      response elicited by LPS attenuated by APAP with supraspinal pain modulatory
      mechanisms.

PMID- 18639581
TI  - Motivation, self-efficacy, physical activity and nutrition in college students:
      randomized controlled trial of an internet-based education program.
AB  - OBJECTIVE: MyStudentBody.com-Nutrition (MSB-N) is an internet-based nutrition and
      physical activity education program for college students. METHOD: Students from
      six universities (N=476) in the U.S. were randomly assigned in the fall of 2005
      to one of three groups: MSB-N (Experimental I), MSB-N plus Booster (Experimental
      II), or an attention placebo control group. RESULTS: Experimental I and II group
      participants increased their fruit and vegetable intake by .33 and .24 servings,
      respectively, relative to the control group at post-test. Both experimental
      groups improved their motivation to change eating behaviors (p<.05) and were also
      more likely to increase their social support and self-efficacy for dietary change
      (p's<.05). Experimental groups also improved their attitude toward exercise
      (p<.05), but no behavioral changes in physical activity were noted. CONCLUSION:
      MyStudentBody.com-Nutrition is an effective internet-based program that may have
      wide applicability on college campuses for nutrition education and promoting
      change in health behaviors.

PMID- 18639582
TI  - Absence of intravitreal bevacizumab-induced neuronal toxicity in the retina.
AB  - Bevacizumab is a complete humanized monoclonal antibody directed against all
      isoforms of vascular endothelial growth factor (VEGF). It was originally used as
      a first-line treatment for metastatic colorectal cancer. Recently, intravitreal
      bevacizumab has been effectively applied to vasoproliferative diseases, such as
      retinal and choroidal neovascularization. However, it is known that intravenous
      administration of bevacizumab in the treatment of cancer can lead to serious
      adverse events, such as congestive heart failure, thromboembolism, and
      neuropathy. In this study, we showed that very high concentrations of
      intravitreal bevacizumab, even up to 15 times the dose normally used in human
      clinical applications, (1microl, 25mg/ml), caused no definite histological
      abnormalities and no significant increase in apoptotic cell death in the mouse
      retina at 4 weeks after treatment. Moreover, intravitreal bevacizumab induced no
      neuronal toxicity in the retina. Even in high concentrations, bevacizumab caused
      no changes in the viability of retinal neurons or the expression of
      neurofilament, a marker of neuronal differentiation. Therefore, we believe that
      intravitreal bevacizumab has therapeutic potential for the treatment of retinal
      and choroidal neovascularization and has the added benefit of exhibiting no acute
      or chronic toxicity in retinal neurons.

PMID- 18639583
TI  - Role of the striatum in the humoral immune response to thymus-independent and
      thymus-dependent antigens in rats.
AB  - Since the role of striatal GABAergic medium-sized spiny (MSP) neurons in the
      modulation of the immune responses is largely unknown, we evaluated the humoral
      immune response in rats with bilateral lesion of the striatum caused by
      quinolinic acid, which destroys MSP neurons. Sham-operated rats and those with
      striatal lesions were immunized either with TNP-LPS, a T-independent antigen type
      1, or one of several T-dependent antigens: ovoalbumin, bovine serum albumin,
      lysozyme, sheep red blood cells (SRBC) or outer membrane proteins (OMP) of
      Salmonella enterica serovar Typhimurium. The specific levels of serum IgM and
      IgG, as well as intestinal IgA antibodies were determined either by enzyme-linked
      immunosorbent assay (ELISA) or a haemagglutination assay 5 or 7 days after
      immunization. Our results show that the lesion of striatal MSP neurons attenuated
      the primary antibody response to the T-independent antigen type 1 (TNP-LPS), but
      increased the antibody response to T-dependent antigens (proteins, SRBC and OMP),
      indicating that the striatal neurons modulate the humoral immune response in
      rats. The mechanisms involved are probably related to a reduction in both the
      number of B cells and the expression of caveolin-1 in the spleen, as well as an
      increase in the number of CD4(+) T cells and in corticosterone levels of the
      serum.

PMID- 18639584
TI  - Detection and discrimination of WU/KI polyomaviruses by real-time PCR with
      melting curve analysis.
AB  - WU and KI polyomaviruses are novel viruses of the Polyomaviridae family, which
      have been identified recently in respiratory secretions from patients with acute
      respiratory tract infection. Their potential role in respiratory disease is still
      unclear and requires additional investigation. To facilitate further studies and
      diagnosis, a real-time PCR with melting curve analysis was optimized and
      evaluated to detect WU and KI polyomaviruses. Primers specific for the VP1 gene
      were designed from regions conserved among WU and KI polyomaviruses which
      provided amplification products of 198 and 231bp corresponding to WU and KI,
      respectively and thus yielded a difference in melting temperature (Tm) between WU
      and KI polyomaviruses. The assay proved highly specific for WU and KI
      polyomaviruses as no cross amplification was detected with other respiratory
      viruses or human genomic DNA. The assay was also highly sensitive with a
      detection limit as low as 10copies/microL for both WU and KI polyomaviruses. The
      performance of the real-time PCR assay was evaluated in terms of amplification
      efficiency (92%). Finally, the assay was validated using DNA extracted from
      clinical respiratory specimens for WU and KI polyomaviruses and the results were
      confirmed by direct nucleotide sequencing. The results obtained by melting curve
      analysis were in perfect agreement with nucleotide sequencing. In conclusion,
      this method is advantageous because it is rapid, specific, sensitive,
      reproducible, accurate, cost-effective and thus, would be feasible and attractive
      for large-scale analysis aimed at investigating the clinical role of WU and KI
      polyomaviruses.

PMID- 18639585
TI  - Use of primers with 5' non-complementary sequences in RT-PCR for the detection of
      nepovirus subgroups A and B.
AB  - Two generic PCR protocols were developed to detect nepoviruses in subgroups A and
      B using degenerate primers designed to amplify part of the RNA-dependent RNA
      polymerase (RdRp) gene. It was observed that detection sensitivity and
      specificity could be improved by adding a 12-bp non-complementary sequence to the
      5' termini of the forward, but not the reverse, primers. The optimized PCR
      protocols amplified a specific product ( approximately 340bp and approximately
      250bp with subgroups A and B, respectively) from all 17 isolates of the 5 virus
      species in subgroup A and 3 species in subgroup B tested. The primers detect
      conserved protein motifs in the RdRp gene and it is anticipated that they have
      the potential to detect unreported or uncharacterised nepoviruses in subgroups A
      and B.

PMID- 18639586
TI  - A novel recombinant bacterial vaccine strain expressing dual viral antigens
      induces multiple immune responses to the Gag and gp120 proteins of HIV-1 in
      immunized mice.
AB  - Recombinant Salmonella enterica serovar Typhi can function as a live vector to
      deliver foreign antigens to the mammalian immune system and induce both mucosal
      and systemic immunity. In this study, we generated a recombinant Salmonella Typhi
      strain pilS-pilT-Gag+ (pVAX1-gp120) harboring the human immunodeficiency virus
      (HIV) gag gene integrated into the bacterial chromosome and gp120 gene carried by
      a plasmid. Mice inoculated with this recombinant bacterium through intranasal
      route produced high titers of IgG to gp120 in sera and IgA to gp120 in fecal
      washes. In addition, Gag-specific and gp120-specific cytotoxic T lymphocyte (CTL)
      responses were observed in sorted spleen lymphocytes of immunized mice. These
      results demonstrated that this recombinant Salmonella Typhi strain elicits
      multiple immune responses against both Gag and gp120 antigens of HIV, and thus
      would be a potential vaccine candidate to the prevention of HIV/AIDS.

PMID- 18639588
TI  - Impaired anorectic effect of leptin in neurotensin receptor 1-deficient mice.
AB  - Neurotensin plays a role in regulating feeding behavior. Central injection of
      neurotensin reduces food intake and the anorectic effect of neurotensin is
      mediated through neurotensin receptor 1 (Ntsr1). Ntsr1-deficient mice are
      characterized by mild hyperphagia and overweight without hyperleptinemia. The
      mechanism by which Ntsr1-deficient mice develop these metabolic abnormalities is
      not well understood. Leptin, secreted by adipocytes, regulates food intake by
      acting on hypothalamic neurons including neurotensin-producing neurons. Since the
      anorectic effect of leptin is blocked by neurotensin receptor antagonist, we
      hypothesized that the anorectic effect of leptin is mediated through Ntsr1 in the
      central nervous system and that decreased sensitivity to the anorectic effect of
      leptin contributes to metabolic perturbations in Ntsr1-deficient mice. To address
      this hypothesis, we examined the effect of intracerebroventricular (i.c.v.)
      administration of leptin on food intake in Ntsr1-deficient mice. A single i.c.v.
      injection of leptin caused robust reductions in food intake in wild-type mice.
      These effects were markedly attenuated in Ntsr1-deficient mice. These data are
      consistent with our hypothesis that the anorectic effect of leptin is at least
      partly mediated through central Ntsr1 and that the leptin-Ntsr1 signaling pathway
      is involved in the regulation of food intake. Our data also suggest that the lack
      of Ntsr1 reduces sensitivity to the anorectic action of leptin, causing
      hyperphagia and abnormal weight gain.

PMID- 18639589
TI  - Food deprivation-like effects of neuropeptide Y on heroin self-administration and
      reinstatement of heroin seeking in rats.
AB  - Numerous findings suggest that drug seeking and ingestive behaviors share common
      neurobiological mechanisms, but the relevant pathways are unknown. Dietary
      manipulations result in changes in endocrine the and/or neuropeptide signals,
      such as the hormones leptin and ghrelin, which are dynamically linked to energy
      balance and the regulation of feeding behavior. We have recently demonstrated
      that food deprivation-induced reinstatement of heroin seeking can be blocked with
      leptin, and others have suggested a role for ghrelin in drug-related behaviors.
      The feeding-relevant effects of leptin and ghrelin involve the inhibition or
      activation, respectively, of neuropeptide Y/agouti-related peptide (NPY/AGRP)
      neurons in the hypothalamus. However, the effects of NPY, a highly potent
      orexigenic peptide, on drug-related behaviors have not been thoroughly studied.
      Here we examined the effect of acute NPY administration on the rate of heroin
      self-administration and the reinstatement of extinguished heroin-seeking
      behavior. Heroin intake (0.05mg/kg/infusion) was tested using a self
      administration procedure (FR-1), 10-min post-NPY injections (0.0, 4.0, and
      10microg/rat, ICV). In a different group of rats, NPY-induced reinstatement (0.0,
      4.0, and 10microg/rat, ICV) of extinguished heroin seeking was assessed. NPY
      injections increased on-going heroin self-administration, and induced a
      reinstatement of extinguished heroin-seeking behavior. These findings suggest
      that NPY can modulate the rewarding and conditioned reinforcing effects of drugs
      of abuse.

PMID- 18639590
TI  - Expression and substrate specificity of a recombinant cysteine proteinase B of
      Leishmania braziliensis.
AB  - The cysteine proteinase B of Leishmania parasites is an important virulence
      factor. In this study we have expressed, isolated and characterized for the first
      time a recombinant CPB from Leishmania braziliensis, the causative agent of
      mucocutaneous leishmaniosis. The mature region of the recombinant CPB shares a
      high percentage identity with its Leishmania mexicana CPB2.8 (rCPB2.8DeltaCTE)
      counterpart (76.36%) and has identical amino acid residues at the S(1), catalytic
      triad and S'(1) subsites. Nevertheless, when the kinetics of substrate hydrolysis
      was measured using a combinatorial library of internally quenched fluorescent
      peptides based upon the lead sequence Abz-KLRSSKQ-EDDnp, significant differences
      were obtained. These results suggest that the differences in substrate
      utilization observed between the L. mexicana and L. braziliensis CPs must be
      related to amino acid modifications outside the core of the active site cleft.
      Moreover, a potent inhibitor with Pro at P1 and high affinity for L. braziliensis
      recombinant CPB showed less affinity to L. mexicana CPB 2.8, which preferred Phe,
      Leu, and Asn at the same position.

PMID- 18639592
TI  - Tau binds both subunits of calcineurin, and binding is impaired by calmodulin.
AB  - Calcineurin, an important protein Ser/Thr phosphatase which acts on tau in vivo,
      is a heterodimer of a catalytic subunit, calcineurin A, and a regulatory subunit,
      calcineurin B, and is unique in being regulated by calmodulin. Here, we find that
      both subunits of calcineurin bind tau, and calmodulin interferes with the
      association between calcineurin and tau. The domains of both subunits of
      calcineurin and tau involved in binding are mapped. We also investigate the
      functional consequences of the interactions between both subunits of calcineurin,
      tau and calmodulin, and reveal the interactions affect dephosphorylation of tau
      by calcineurin and contribute to the balance of phosphorylation and
      dephosphorylation of tau in vivo. Our findings may be of potential significance
      in neuronal physiology and also in neurodegenerative disorders. They shed some
      light on how the interactions might control the phosphorylation state of tau
      under physiological conditions, and provide new insights into the treatment of
      tauopathies such as Alzheimer's disease.

PMID- 18639591
TI  - Genetic evidence for the essential role of PfNT1 in the transport and utilization
      of xanthine, guanine, guanosine and adenine by Plasmodium falciparum.
AB  - The malaria parasite, Plasmodium falciparum, is unable to synthesize the purine
      ring de novo and is therefore wholly dependent upon purine salvage from the host
      for survival. Previous studies have indicated that a P. falciparum strain in
      which the purine transporter PfNT1 had been disrupted was unable to grow on
      physiological concentrations of adenosine, inosine and hypoxanthine. We have now
      used an episomally complemented pfnt1Delta knockout parasite strain to confirm
      genetically the functional role of PfNT1 in P. falciparum purine uptake and
      utilization. Episomal complementation by PfNT1 restored the ability of pfnt1Delta
      parasites to transport and utilize adenosine, inosine and hypoxanthine as purine
      sources. The ability of wild-type and pfnt1Delta knockout parasites to transport
      and utilize the other physiologically relevant purines adenine, guanine,
      guanosine and xanthine was also examined. Unlike wild-type and complemented P.
      falciparum parasites, pfnt1Delta parasites could not proliferate on guanine,
      guanosine or xanthine as purine sources, and no significant transport of these
      substrates could be detected in isolated parasites. Interestingly, whereas
      isolated pfnt1Delta parasites were still capable of adenine transport, these
      parasites grew only when adenine was provided at high, non-physiological
      concentrations. Taken together these results demonstrate that, in addition to
      hypoxanthine, inosine and adenosine, PfNT1 is essential for the transport and
      utilization of xanthine, guanine and guanosine.

PMID- 18639593
TI  - A method for analysing phosphatase activity in aquatic bacteria at the single
      cell level using flow cytometry.
AB  - It has been demonstrated that ELF97-phosphate (ELF-P) is a useful tool to detect
      and quantify phosphatase activity of phytoplankton populations at a single cell
      level. Recently, it has been successfully applied to marine heterotrophic
      bacteria in culture samples, the cells exhibiting phosphatase activity being
      detected using epifluorescence microscopy. Here, we describe a new protocol that
      enables the detection of ELF alcohol (ELFA), the product of ELF-P hydrolysis,
      allowing the detection of phosphatase positive bacteria, using flow cytometry.
      Bacteria from natural samples must be disaggregated and, in oligotrophic waters,
      concentrated before they can be analyzed by flow cytometry. The best efficiency
      for disaggregating/separating bacterial cell clumps was obtained by incubating
      the sample for 30 min with Tween 80 (10 mg l(-1), final concentration). A
      centrifugation step (20,000 g; 30 min) was required in order to recover all the
      cells in the pellet (only 7+/-2% of the cells were recovered from the
      supernatant). The cells and the ELFA precipitates were resistant to these
      treatments. ELFA-labelled samples were stored in liquid nitrogen for up to four
      months before counting without any significant loss in total or ELFA-labelled
      bacterial cell abundance or in the ELFA fluorescence intensity. We describe a new
      flow cytometry protocol for detecting and discriminating the signals from both
      ELFA and different counterstains (4',6-diamidino-2-phenylindole (DAPI) and
      propidium iodide (PI)) necessary to distinguish between ELFA-labelled and non
      ELFA-labelled heterotrophic bacteria. The method has been successfully applied in
      both freshwater and marine samples. This method promises to improve our
      understanding of the physiological response of heterotrophic bacteria to P
      limitation.

PMID- 18639587
TI  - Serotonergic mechanisms in addiction-related memories.
AB  - Drug-associated memories are a hallmark of addiction and a contributing factor in
      the continued use and relapse to drugs of abuse. Repeated association of drugs of
      abuse with conditioned stimuli leads to long-lasting behavioral responses that
      reflect reward-controlled learning and participate in the establishment of
      addiction. A greater understanding of the mechanisms underlying the formation and
      retrieval of drug-associated memories may shed light on potential therapeutic
      approaches to effectively intervene with drug use-associated memory. There is
      evidence to support the involvement of serotonin (5-HT) neurotransmission in
      learning and memory formation through the families of the 5-HT(1) receptor (5
      HT(1)R) and 5-HT(2)R which have also been shown to play a modulatory role in the
      behavioral effects induced by many psychostimulants. While there is a paucity of
      studies examining the effects of selective 5-HT(1A)R ligands, the available
      dataset suggests that 5-HT(1B)R agonists may inhibit retrieval of cocaine
      associated memories. The 5-HT(2A)R and 5-HT(2C)R appear to be integral in the
      strong conditioned associations made between cocaine and environmental cues with
      5-HT(2A)R antagonists and 5-HT(2C)R agonists possessing potency in blocking
      retrieval of cocaine-associated memories following cocaine self-administration
      procedures. The complex anatomical connectivity between 5-HT neurons and other
      neuronal phenotypes in limbic-corticostriatal brain structures, the heterogeneity
      of 5-HT receptors (5-HT(X)R) and the conflicting results of behavioral
      experiments which employ non-specific 5-HT(X)R ligands contribute to the
      complexity of interpreting the involvement of 5-HT systems in addictive-related
      memory processes. This review briefly traces the history of 5-HT involvement in
      retrieval of drug-cue associations and future targets of serotonergic
      manipulation that may reduce the impact that drug cues have on addictive behavior
      and relapse.

PMID- 18639594
TI  - Detection of Trichinella spiralis, T. britovi and T. pseudospiralis in muscle
      tissue with real-time PCR.
AB  - Infections caused by Trichinella species occur throughout the world in many wild
      and domestic animals resulting in trichinellosis in men. In Europe, domestic pigs
      are predominantly infected by three Trichinella species: T. spiralis, T. britovi
      and T. pseudospiralis. Present methods for detection of Trichinella spp.
      (compressorium method, artificial digestion) do not always sufficiently recognize
      Trichinella larvae and these techniques are labor-intensive, time consuming and
      do not differentiate isolates on the species level since there are no
      distinguishing morphological features. Additionally, conventional PCRs cannot
      quantify numbers of larvae in infectious material. In order to better meet these
      requirements, we developed a real-time PCR assay for the accurate, rapid and
      specific identification of the three common European species of the genus
      Trichinella. The assay targets the large subunit of the mitochondrial rRNA (rrnL)
      and enables sensitive determination and discrimination of larvae in muscle tissue
      samples. The real-time PCR assay was developed and validated using reference and
      field strains from T. spiralis, T. britovi and T. pseudospiralis. In the
      described real-time PCR assay, the melting points of specific amplificates were
      always discernable via the melting curve from melting points of unspecific
      amplificates. This is important for the methods workflow because only C(T) values
      connected with the additional melting curve analysis allow a distinction of the
      individual species with confidence. The sensitivity of the technique enabled
      detection down to 0.1 Trichinella larva per gram meat sample. High disruption
      levels of tissues by mincing generally resulted in higher sensitivities than
      protocols without mincing. With its short completion time as well as accurate and
      specific detection of selected species this assay could become a convenient tool
      for the fast detection of Trichinella larvae in meat.

PMID- 18639595
TI  - Adhesion and ultrasound-induced delivery from monodisperse microbubbles in a
      parallel plate flow cell.
AB  - Microbubbles, ultrasound contrast agents currently in development as
      ultrasonically activated drug delivery vehicles, were studied using a novel flow
      cell design. The flow cell combined ultrasound compatibility, a planar optical
      configuration, and a Cartesian orientation of buoyant, shear, and acoustic
      forces. The set-up enabled measurements of buoyant rise and adhesive sensitivity
      to shear forces for individual biotinylated, monodisperse, polymer-shelled
      microbubbles near a NeutrAvidin-coated polystyrene substrate. Analysis of the
      velocity history demonstrated that adhesion depended on the buoyant rise to the
      surface before attachment to the substrate: only when the distance parallel to
      the substrate in the flow direction was between 10 and 20 microm from the
      stopping position could specific molecular recognition events occur. Low
      intensity ultrasound caused strong two-dimensional mobility leading to reversible
      clustering of microbubbles, even though they interacted strongly with the
      substrate through biotin-NeutrAvidin bonds. At higher acoustic pressure, local
      gas release took place. With sufficient acoustic intensity, the agents
      demonstrate potential as large payload carriers for biomolecularly targeted
      therapeutic delivery. However, difficulties may limit the range of targeting
      applications: large sizes may render microbubbles susceptible to detachment at
      the shearing forces present in many regions of the vasculature and secondary
      radiation forces may reduce targeting effectiveness.

PMID- 18639596
TI  - Dendritic multishell architectures for drug and dye transport.
AB  - Here we present the efficiency and versatility of newly developed core-multishell
      nanoparticles (CMS NPs), to encapsulate and transport the antitumor drugs
      doxorubicin hydrochloride (Dox), methotrexate (Mtx) and sodium ibandronate (Ibn)
      as well as dye molecules, i.e., a tetrasulfonated indotricarbocyanine (ITCC) and
      nile red. Structurally, the CMS NPs are composed of hyperbranched poly(ethylene
      imine) core functionalized by alkyl diacids connected to monomethyl poly(ethylene
      glycol). In order to evaluate their transport in aqueous media in vitro, we have
      used and compared SEC, UV, ITC, and NMR techniques. We observed that the CMS NPs
      were able to spontaneously encapsulate and transport Dox, Mtx and nile red in
      both organic and aqueous media as determined by SEC and UV-VIS spectroscopy. For
      the VIS transparent Ibn Isothermal Titration Calorimetric (ITC) experiments show
      an exothermic interaction with the CMS NPs. The enthalpic stabilization (DeltaH)
      upon encapsulation was in the order of approximately 7 kcals/mol which indicates
      stable interaction between Ibn and nanoparticles. A T(1) inversion recovery NMR
      experiment was carried out for 31P and 1H nuclei of Ibn and an increment of spin
      lattice relaxation time for respective nuclei was observed upon encapsulation.
      CMS NPs were also found to encapsulate ITCC dye with stoichiometry of 6-8
      molecules/nanocarrier. For in vivo imaging studies the dye loaded CMS NPs were
      injected to F9 teratocarcinoma bearing mice and a strong contrast was observed in
      the tumor tissues compared to free dye after 6 h of administration.

PMID- 18639597
TI  - Identification and kainic acid-induced up-regulation of low-affinity p75
      neurotrophin receptor (p75NTR) in the nigral dopamine neurons of adult rats.
AB  - Parkinson's disease is a common and severe debilitating neurological disease that
      results from massive and progressive degenerative death of dopamine neurons in
      the substantia nigra, but the mechanisms of neuronal degeneration and disease
      progression remains largely obscure. We are interested in possible implications
      of low-affinity p75 neurotrophin receptor (p75NTR), which may mediate neuronal
      apoptosis in the central nervous system, in triggering cell death of the nigral
      dopamine neurons. The RT-PCR and immunohistochemistry were carried out to detect
      if p75NTR is expressed in these nigral neurons and up-regulated by kainic acid
      (KA) insult in adult rats. It revealed p75NTR-positive immunoreactivity in the
      substantia nigra, and co-localization of p75NTR and tyrosine hydroxylase (TH) was
      found in a large number of substantia nigra neurons beside confirmation of p75NTR
      in the choline acetyltransferase (ChAT)-positive forebrain neurons. Cell count
      data further indicated that about 47-100% of TH-positive nigral neurons and 98
      100% of ChAT-positive forebrain neurons express p75NTR. More interestingly,
      significant increasing in both p75NTR mRNA and p75NTR-positive neurons occurred
      rapidly following KA insult in the substantia nigra of animal model. The present
      study has provided first evidence on p75NTR expression and KA-inducing p75NTR up
      regulation in substantia nigra neurons in rodent animals. Taken together with
      previous data on p75NTR functions in neuronal apoptosis, this study also suggests
      that p75NTR may play important roles in neuronal cell survival or excitotoxic
      degeneration of dopamine neurons in the substantia nigra in pathogenesis of
      Parkinson's disease in human beings.

PMID- 18639598
TI  - Cytotoxic T-lymphocyte-mediated killing of human pancreatic islet cells in vitro.
AB  - Cytotoxic T lymphocytes (CTL) are believed to play an essential role in beta-cell
      destruction leading to development of type 1 diabetes and allogeneic islet graft
      failure. We aimed to identify the mechanisms used by CTL to kill human beta
      cells. CTL clones that recognize epitopes from influenza virus and Epstein-Barr
      virus restricted by human leukocyte antigen (HLA)-A0201 and -B0801, respectively,
      were used to investigate the susceptibility of human beta cells to CTL. In a
      short-term (5-hour) assay, CTL killed human islet cells of the appropriate major
      histocompatibility complex (MHC) class I type that had been pulsed with viral
      peptides. Killing was increased by pretreating islets with interferon gamma that
      increases MHC class I on target cells. Killing was abolished by incubation of CTL
      with the perforin inhibitor concanamycin A. The Fas pathway did not contribute to
      killing because blocking with neutralizing anti-Fas ligand antibody did not
      significantly reduce beta-cell killing. In conclusion, we report a novel way of
      investigating the interaction between CTL and human islets. Human islets were
      rapidly killed in vitro by MHC class I-restricted CTL predominantly by the
      granule exocytosis pathway.

PMID- 18639599
TI  - Induction of opsonophagocytic killing activity with pneumococcal conjugate
      vaccine in human immunodeficiency virus-infected Ugandan adults.
AB  - The levels of IgG determined by ELISA may have limited relevance in human
      immunodeficiency virus (HIV)-infected adults because of non-functional
      antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized
      with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a 2
      month interval, and the opsonophagocytic killing (OPK) titers against serotype 4
      or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera
      were determined. Significant increases were found in the OPK titers and IgG
      levels for both serotypes after CV vaccination irrespective of HIV status.
      Increases in IgG levels and OPK titers were largely dependent on the CD4(+) cell
      counts, except for increases in the IgG levels for serotype 4. The proportions
      with serum OPK titer equal to or greater than 8 were 0-4.3% for serotype 4 and
      26.7-42.9% for serotype 14 before vaccination, but the proportions increased up
      to 43.3-86.2% for serotype 4 and 63.3-96.6% for serotype 14 in all three groups 2
      months after CV vaccination. The serum OPK titers remained at levels higher than
      the pre-vaccination level for at least 8 months after CV vaccination. A single
      dose of CV could afford some protective immunity in HIV-infected African adults
      before the introduction of antiretroviral therapy.

PMID- 18639600
TI  - Anti-tumor effect of DNA-based vaccination and dSLIM immunomodulatory molecules
      in mice with Ph+ acute lymphoblastic leukaemia.
AB  - Since the prognosis of patients with Philadelphia chromosome positive acute
      lymphoblastic leukaemia (Ph+ ALL) still remains poor, new relapse prevention
      strategies are needed. We evaluated the pre-immunization of mice with DNA-based
      vaccines subsequently challenged by the syngeneic Ph+ ALL cell line BM185.
      Ballistic transfer of minimalistic immunogenically defined gene expression
      (MIDGE) vectors encoding a BCR-ABLp185 fusion specific peptide or GM-CSF were
      used for in vivo transfection. DNA-based double stem-loop immunomodulators
      (dSLIM) were used as immune adjuvant. We present survival and functional data
      that DNA-based vaccination with BCR-ABLp185 fusion specific sequences, GM-CSF and
      dSLIM leads to an anti-tumor effect in mice challenged with a lethal Ph+ ALL dose
      and this effect depends on leukaemia-specific sequences.

PMID- 18639601
TI  - Safe administration of an inactivated virosomal adjuvanted influenza vaccine in
      asthmatic children with egg allergy.
AB  - In order to evaluate whether the virosomal adjuvanted influenza vaccine that has
      been shown to have the lowest egg protein content (Inflexal V, Berna Biotech)
      could be administered to children with even severe egg allergy without any risk
      of allergic reactions, we used epicutaneous skin testing with the undiluted
      vaccine in 88 asthmatic children (44 with and 44 without egg allergy), none of
      whom had a positive response. They were then vaccinated with the whole dose of
      Inflexal V intramuscularly in a one-dose protocol, and the occurrence of any
      immediate or delayed adverse events were actively monitored for 28 days. The
      results showed the safety of the administration, and demonstrated that Inflexal V
      can be safely given without performing a vaccine skin test in children with any
      kind of egg allergy.

PMID- 18639602
TI  - Aseptic meningitis after transmission of the Leningrad-Zagreb mumps vaccine from
      vaccinee to susceptible contact.

PMID- 18639603
TI  - Environmental tobacco smoke (ETS) evaluation of a third-generation electrically
      heated cigarette smoking system (EHCSS).
AB  - This sub-study of a randomized, controlled, forced-switching, open-label,
      parallel-group, clinical study compared environmental tobacco smoke (ETS)
      produced when 60 male and female adult smokers switched to a third-generation
      electrically heated cigarette smoking system (EHCSS), continued to smoke a
      conventional cigarette (CC), or stopped smoking (No-smoking). Concentrations of
      air constituents including respirable suspended particulate (RSP), carbon
      monoxide (CO), ammonia and total volatile organic compounds (TVOCs) and ETS
      markers including solanesol-related particulate matter (Sol-PM), ultraviolet
      absorbing particulate matter (UVPM), fluorescent particulate matter (FPM),
      nicotine and 3-ethenyl pyridine (3-EP) were measured in a ventilated, furnished
      conference room over a 2-h period on separate occasions for each smoking
      condition. When the EHCSS was used, concentrations of CO and most ETS markers
      were in the same range as during no-smoking. Concentrations of ammonia were
      reduced by 41% and concentrations of other selected constituents of ETS were
      reduced by 87-99% in the air of a room in which EHCSS cigarettes were smoked as
      compared to concentrations in the same room when conventional cigarettes were
      smoked. Switching from conventional cigarette smoking to the EHCSS resulted in
      substantial reductions in concentrations of several markers of environmental
      tobacco smoke.

PMID- 18639604
TI  - Reducing added sugar intake in Norway by replacing sugar sweetened beverages with
      beverages containing intense sweeteners - a risk benefit assessment.
AB  - A risk benefit assessment in Norway on the intake of added sugar, intense
      sweeteners and benzoic acid from beverages, and the influence of changing from
      sugar sweetened to diet beverages was performed. National dietary surveys were
      used in the exposure assessment, and the content of added sugar and food
      additives were calculated based on actual contents used in beverages and sales
      volumes provided by the manufactures. The daily intake of sugar, intense
      sweeteners and benzoic acid were estimated for children (1- to 13-years-old) and
      adults according to the current intake level and a substitution scenario where it
      was assumed that all consumed beverages contained intense sweeteners. The change
      from sugar sweetened to diet beverages reduced the total intake of added sugar
      for all age groups but especially for adolescent. This change did not result in
      intake of intense sweeteners from beverages above the respective ADIs. However,
      the intake of acesulfame K approached ADI for small children and the total intake
      of benzoic acid was increased to above ADI for most age groups. The highest
      intake of benzoic acid was observed for 1- to 2-year-old children, and benzoic
      acid intake in Norwegian children is therefore considered to be of special
      concern.

PMID- 18639605
TI  - Gene transfer events and their occurrence in selected environments.
AB  - Genes encoding virulence determinants are transferred between species in many
      different environments. In this review we describe gene transfer events to and
      from different species of bacteria, from bacteria to plants, and from plants to
      bacteria. Examples of the setting for these transfer events include: the GI
      tract, the rumen, the oral cavity, and in food matrixes. As a case study, the
      flux of virulence factors from E.coli O157:H7 is described as an example of gene
      flow in the environment.

PMID- 18639606
TI  - Piperine, the potential functional food for mood and cognitive disorders.
AB  - The effect of piperine, the main alkaloid from piper nigrum, on the central
      nervous system is not clearly known until now. In the present study, male Wistar
      rats were administered piperine at various doses ranging from 5, 10 and 20mg/kg
      BW once daily for 4 weeks and the animals were determined the
      neuropharmacological activity after single, 1, 2, 3 and 4 weeks of treatment. The
      results showed that piperine at all dosage range used in this study possessed
      anti-depression like activity and cognitive enhancing effect at all treatment
      duration. Therefore, piperine may be served as the potential functional food to
      improve brain function. However, further investigations about precise underlying
      mechanism are still required.

PMID- 18639607
TI  - Toxicological evaluation and bioavailability of (14)C-fenitrothion bound residues
      on soybeans towards experimental animals.
AB  - Under local practice of Egyptian conditions, the application of (14)C
      fenitrothion on soybeans at a dose of 10mg insecticide/kg grains, led to the
      formation of 21% of (14)C-bound residues (non-extractable) after 24 weeks of
      storage. The external residues were 20% and the internal extracts were 55% of the
      applied dose. Feeding studies on rats revealed that bound residues were
      bioavailable. After feeding rats for three days with bound (14)C-fenitrothion
      residues, the main portion of radioactivity was eliminated via expired air (42%),
      urine (20%) and feces (11.5%). About 15% of the administered radioactivity was
      distributed among various organs as, liver, kidney, lung, fat, intestine, blood,
      heart, and brain. Toxicity of bound residues of (14)C-fenitrothion in stored
      soybeans was studied in mice through feeding experiments for three months at a
      concentration of 1.9 mg/kg. The maximum inhibition in plasma and erythrocyte
      cholinesterase activity was observed 22.5%, 18.9% and 8.6%, 9% after one and
      seven days, respectively. The obtained results showed a slight significant
      elevation after three months in the activity of liver enzymes alanine amino
      transferase, aspartate amino transferase and alkaline phosphatase. A moderate
      increase in blood urea nitrogen and creatinine concentration was observed in the
      treated groups at the end of the experimental period. The detected levels of
      albumin and total protein showed no significant compared to the control values,
      of controlled animals, after three months.

PMID- 18639609
TI  - Study of biocomplexity in an aquatic ecosystem through ascendency.
AB  - The ascendancy concept aims at quantitatively describing the growth and
      development of an ecosystem as whole. Growth is an increase in the total system
      throughflow, while development is taken to be a rise in the average mutual
      information inherent in the network flow structure. As an ecosystem matures and
      goes through a series of successional stages, its ascendancy exhibits a
      propensity to increase. In any ecosystem the equilibrium condition may gradually
      turn into a chaotic situation for different reasons. In this paper a model is
      proposed of an aquatic ecosystem comprising of three groups, viz., phytoplankton,
      zooplankton and fish. Rate parameters are changed according to the change of the
      size of the organisms. The model is run in different conditions with gradual
      decrement of the body sizes of zooplankton. Allometric principle of the
      relationship of body size of zooplankton and two rate parameters (growth rate and
      half saturation constant) are incorporated in this model. According to allometric
      principle gradual decrement of body sizes of zooplankton consequently increases
      the grazing rate and decreases the half-saturation constant of this organisms.
      The system exhibits different states (equilibrium point--stable limit cycle-
      doubling and ultimately chaos) by gradual increase of zooplankton grazing rate
      and decrease of half-saturation constant. This paper tests the high level of
      ascendancy of the systems at the edge of oscillation before starting of the
      chaos. This high level of throughflow and mutual information, i.e. Ascendency
      supports the hypothesis that the system can coordinate the most complex behavior
      and shows maximum biocomplexity in this situation.

PMID- 18639610
TI  - TNF-alpha polymorphisms are associated with obsessive-compulsive disorder.
AB  - INTRODUCTION: Several lines of evidence support an immunologic involvement in
      obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients
      with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum
      disorders among relatives of RF probands. Tumor necrosis factor alpha is a
      proinflammatory cytokine involved in RF and other autoimmune diseases.
      Polymorphisms in the promoter region of the TNFA gene have been associated with
      RF. Given the association between OCD and RF, the goal of the present study was
      to investigate a possible association between polymorphisms within the promoter
      region of TNFA and OCD. MATERIALS AND METHODS: Two polymorphisms were
      investigated: -308 G/A and -238 G/A. The allelic and genotypic frequencies of
      these polymorphisms were examined in 111 patients who fulfilled DSM-IV criteria
      for OCD and compared with the frequencies in 250 controls. RESULTS: Significant
      associations were observed between both polymorphisms and OCD. For -238 G/A, an
      association between the A allele and OCD was observed (chi(2)=12.05, p=0.0005). A
      significant association was also observed between the A allele of the -308 G/A
      polymorphism and OCD (chi(2)=7.09, p=0.007). Finally, a haplotype consisting of
      genotypes of these two markers was also examined. Significant association was
      observed for the A-A haplotype (p=0.0099 after correcting for multiple testing).
      DISCUSSION: There is association between the -308 G/A and -238 G/A TNFA
      polymorphisms and OCD in our Brazilian sample. However, these results need to be
      replicated in larger samples collected from different populations.

PMID- 18639608
TI  - HPA axis function in male caregivers: effect of the monoamine oxidase-A gene
      promoter (MAOA-uVNTR).
AB  - Caregiving stress is associated with negative health outcomes. Neuroendocrine
      functioning may be a mediator of such outcomes. The MAOA gene regulates activity
      of neurotransmitters involved with neuroendocrine responses to stress.
      Differences in polymorphisms of this gene have been shown to influence
      susceptibility to stress. Therefore, we examined allelic variation in MAOA-uVNTR,
      a functional polymorphism of MAOA, as a moderator of chronic stress effects on
      urinary cortisol excretion in 74 males enrolled in a case/control study of
      caregivers for relatives with dementia. Mixed models analysis of variance were
      used to examine MAOA-uVNTR genotype (3 repeats vs. 3.5/4 repeats) as a moderator
      of the impact of stress (caregiver vs. non-caregiver) on the urinary excretion
      pattern (overnight, daytime, evening) of cortisol. Caregivers with MAOA-uVNTR
      alleles associated with less transcriptional activity (3-repeats) displayed a
      pattern of cortisol excretion -- a decrease from overnight to daytime -- that was
      suggestive of HPA axis blunting, as compared to non-caregivers and those
      caregivers with the more active alleles (3.5/4 repeats) (cortisol p<.043).
      Individuals with less active MAOA-uVNTR alleles who are under chronic stress may
      be at increased risk for exhaustion of the HPA response to such stress.

PMID- 18639611
TI  - Nicotine-induced phosphorylation of phosphorylated cyclic AMP response element
      binding protein (pCREB) in hippocampal neurons is potentiated by agrin.
AB  - The scope of this study was to test whether increased levels of the extracellular
      matrix molecule (ECM) agrin might enhance nicotine effects on those molecular
      mechanisms that initiate neuroadaptative processes in the hippocampus, a key
      brain area for learning and memory. We studied the effects of repetitive
      applications of neuronal agrin to primary hippocampal cell culture on nicotine
      induced phosphorylated cyclic AMP response element-binding protein (pCREB)
      expression, a marker of neuroadaptation, by using immunofluorescence-based
      assessment of pCREB-positive neurons. We also tested agrin effects on nicotine
      induced expression of a marker of metabolic activation, the immediate early gene
      c-fos. Agrin was shown to significantly enhance nicotine-induced pCREB, but not c
      fos, expression. By using Western blotting analysis, cumulative agrin has been
      shown to increase nicotine-induced pCREB phosphorylation. These analyses,
      however, showed that inhibition of the CaMKII pathway blocked general pCREB
      phosphorylation, whereas inhibition of the MAPK pathway potentiated the
      synergistic effect of cumulative agrin and nicotine. These findings suggest that
      increasing the concentration of an ECM molecule, i.e. agrin, may enhance nicotine
      effects on pCREB and that both MAPK and CaMKII signalling may play a regulatory
      role.

PMID- 18639612
TI  - Disturbance of the correlation between hippocampal and septal EEGs during
      epileptogenesis.
AB  - Field potentials of the hippocampus and the medial septal-diagonal band complex
      (MSDB) were recorded in the control and during the kindling stimulation of the
      perforant path in waking guinea pigs. Changes in the correlation of activities of
      these structures during stimulation-evoked seizures (model of acute epilepsy) and
      during epileptogenesis elicited by the kindling (model of chronic epilepsy) were
      analysed. In the control, a high correlation between the background activities of
      the hippocampus and MSDB was observed. In the first days of stimulation at the
      parameters that evoked seizure discharges in the hippocampus, the MSDB did not
      show the epileptiform activity; however, repeated daily stimulation gave rise to
      epileptiform discharges, which increased with time. As a result of kindling, the
      MSDB became capable of generating seizure activity irrespective of the
      hippocampus. The degree of correlation between the activities of the two
      structures sharply decreased during "acute" and "chronic" seizures. In the
      process of kindling, a progressive disintegration of activities of the
      hippocampus and MSDB was revealed, indicating the disturbance of the functioning
      of septohippocampal network during epileptogenesis. The data obtained add to the
      knowledge about the mechanisms of temporal lobe epilepsy and may help to develop
      new approaches to the therapy of this disease.

PMID- 18639613
TI  - Modulation of cortical activity as a result of voluntary postural sway direction:
      an EEG study.
AB  - There is increasing evidence demonstrating the role of the cerebral cortex in
      human postural control. Modulation of EEG both in voltage and frequency domains
      has been observed preceding and following self-paced postural movements and those
      induced by external perturbations. The current study set out to provide
      additional evidence regarding the role of cerebral cortex in human postural
      control by specifically examining modulation of EEG as a function of postural
      sway direction. Twelve neurologically normal subjects were instructed to produce
      self-paced voluntary postural sways in the anterior-posterior (AP) and medial
      lateral (ML) directions. The center of pressure dynamics and EEG both in voltage
      and frequency domains were extracted by averaging and Morlet wavelet techniques,
      respectively. The amplitude of movement-related cortical potentials (MRCP) was
      significantly higher preceding ML sways. Also, time-frequency wavelet
      coefficients (TF) indicated differential modulation of EEG within alpha, beta and
      gamma bands as a function of voluntary postural sway direction. Thus, ML sway
      appear to be more difficult and energy demanding tasks than the AP sway as
      reflected in differential modulation of EEG. These results are discussed within
      the conceptual framework of differential patterns of brain activation as a result
      of postural task complexity.

PMID- 18639614
TI  - Functional and structural modifications during retinal degeneration in the rd10
      mouse.
AB  - Mouse models of retinal degeneration are useful tools to study therapeutic
      approaches for patients affected by hereditary retinal dystrophies. We have
      studied degeneration in the rd10 mice both by immunocytochemistry and TUNEL
      labeling of retinal cells, and through electrophysiological recordings. The cell
      degeneration in the retina of rd10 mice produced appreciable morphological
      changes in rod and cone cells by P20. Retinal cell death is clearly observed in
      the central retina and it peaked at P25 when there were 800 TUNEL-positive cells
      per mm(2). In the central retina, only one row of photoreceptors remained in the
      outer nuclear layer by P40 and there was a remarkable deterioration of bipolar
      cell dendrites postsynaptic to photoreceptors. The axon terminals of bipolar
      cells also underwent atrophy and the inner retina was subject to further changes,
      including a reduction and disorganization of AII amacrine cell population.
      Glutamate sensitivity was tested in rod bipolar cells with the single cell patch
      clamp technique in slice preparations, although at P60 no significant differences
      were observed with age-matched controls. Thus, we conclude that rod and cone
      degeneration in the rd10 mouse model is followed by deterioration of their
      postsynaptic cells and the cells in the inner retina. However, the functional
      preservation of receptors for photoreceptor transmission in bipolar cells may
      open new therapeutic possibilities.

PMID- 18639616
TI  - Prediction of walking recovery after spinal cord injury.
AB  - The recovery of walking function is considered of extreme relevance both by
      patients and physicians. Consequently, in the recent years, recovery of
      locomotion become a major objective of new pharmacological and rehabilitative
      interventions. In the last decade, several pharmacological treatment and
      rehabilitative approaches have been initiated to enhance locomotion capacity of
      SCI patients. Basic science advances in regeneration of the central nervous
      system hold promise of further neurological and functional recovery to be studied
      in clinical trials. Society is making demands for treatment before adequate
      trials have been conducted, but the scientific community has emphasized the need
      for rigorous guidelines and studies. Therefore, a precise knowledge of the
      natural course of walking recovery after SCI and of the factors affecting the
      prognosis for recovery has become mandatory. In the present work we reviewed the
      prognostic factors for walking recovery, with particular attention paid to the
      clinical ones. The prognostic value of some instrumental examinations and of the
      more diffuse pharmacological and surgical interventions has also been reviewed.

PMID- 18639615
TI  - Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is
      required for AMPAR trafficking and acquisition of in vitro classical
      conditioning.
AB  - Brain-derived neurotrophic factor (BDNF) has been implicated in mechanisms of
      synaptic plasticity such as long-term potentiation (LTP), but its role in
      associative learning remains largely unknown. In the present study, we
      investigated the function of BDNF and its receptor tropomyosin-related kinase B
      (TrkB) in an in vitro model of classical conditioning using pond turtles,
      Pseudemys scripta elegans. Conditioning resulted in a significant increase in
      BDNF and phospho (p)-Trk expression. Bath application of antibodies directed
      against TrkB, but not TrkA or TrkC, abolished acquisition of conditioning, as did
      a receptor tyrosine kinase inhibitor K252a and an inhibitor of nitric oxide
      synthase 7-nitroindazole. Significantly, injections of BDNF Ab into the nerve
      roots of presynaptic axonal projections or postsynaptic motor neurons prevented
      acquisition of conditioning, suggesting that BDNF is required on both sides of
      the synapse for modification to occur. The presynaptic proteins synaptophysin and
      synapsin I were increased upon conditioning or BDNF application. Furthermore,
      BDNF application alone mimicked conditioning-induced synaptic insertion of GluR1
      and GluR4 AMPAR subunits into synapses, which was inhibited by co-application of
      BDNF and K252a. Data also show that extracellular signal-regulated kinase (ERK)
      was activated in BDNF-treated preparations. We conclude that coordinate pre- and
      postsynaptic actions of BDNF are required for acquisition of in vitro classical
      conditioning.

PMID- 18639617
TI  - Biology and chemistry of Ginkgo biloba.
AB  - Ginkgo biloba has been existing on earth since 200 million years and is
      considered as a "living fossil". It is among the most sold medicinal plants in
      the world. A number of secondary metabolites representing terpenoids,
      polyphenols, allyl phenols, organic acids, carbohydrates, fatty acids and lipids,
      inorganic salts and amino acids have been isolated from the plant. However, the
      main bioactive constituents are terpene trilactones and flavonoid glycosides
      which are considered responsible for the pharmacological activities of its
      standardized leaf extract. Scattered information is available on the extraction
      and analysis of these pharmacologically important constituents which have been
      compiled in the present review.

PMID- 18639618
TI  - A behavioral analysis of prey detection lateralization and unilateral transfer in
      European starlings (Sturnus vulgaris).
AB  - It has been suggested that birds prefer to use a particular eye while learning to
      detect cryptic prey and that this eye preference enhances foraging performance.
      European starlings (Sturnus vulgaris) with the left, right, or both eyes
      available learned to detect inconspicuous cues associated with the presence of
      hidden prey. Acquisition scores were not significantly different between left and
      right-eyed birds; however, performance in the binocular condition was
      significantly higher than in the two monocular conditions. When binocular birds
      were tested with familiar and unfamiliar cues present simultaneously, the
      familiar cue was selected significantly more often than the unfamiliar cue,
      suggesting that the birds were searching for specific cue features. When
      monocular birds were tested using only the naive eye, performance dropped
      significantly. In right-eyed birds using the naive left eye, performance remained
      at chance levels over transfer trials. However, left-eyed birds using the naive
      right eye had a superior performance compared to the initial acquisition scores
      of right-eyed birds and also showed a significant improvement in performance over
      transfer trials. Thus, although there was no direct evidence of lateralization
      during acquisition, there was unilateral transfer of the prey detection skill
      from the right to the left hemisphere.

PMID- 18639619
TI  - Hepatoprotective activity of Woodfordia fruticosa Kurz flowers against carbon
      tetrachloride induced hepatotoxicity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dried flowers of Woodfordia fruticosa Kurz.
      Family Lythraceae are used in variety of diseases in traditional Indian system of
      medicine including hepatic ailments. AIMS OF STUDY: The aim of present study was
      to validate hepatoprotective activity of flowers of Woodfordia fruticosa Kurz.
      MATERIALS AND METHODS: Petroleum ether (WF1), chloroform (WF2), ethyl alcohol
      (WF3) and aqueous (WF4) extracts of the flowers of Woodfordia fruticosa were
      evaluated for hepatoprotective activity against carbon tetrachloride induced
      hepatotoxicity using biochemical markers, hexobarbitone sleep time,
      bromosulphalein (BSP) clearance test and effect on bile flow and bile solids.
      RESULTS: The aqueous extract (WF4) was most potent among the four extracts
      studied in detail. WF4 showed significant hepatoprotective activity against
      carbon tetrachloride induced hepatotoxicity as evident by restoration of serum
      transaminases, alkaline phosphatase, bilirubin and triglycerides. The restoration
      of microsomal aniline hydroxylase and amidopyrine-N-demethylase activities
      indicated the improvement in functional status of endoplasmic reticulum.
      Restoration of lipid peroxidation and glutathione contents suggests the
      antioxidant property of WF4. The recovery in bromosulphalein clearance and
      stimulation of bile flow suggested the improved excretory and secretary capacity
      of hepatocytes. Light microscopy of the liver tissue further confirmed the
      reversal of damage induced by hepatotoxin. CONCLUSION: Present study showed that
      the aqueous extract of Woodfordia fruticosa significantly restores physiological
      integrity of hepatocytes. WF4 did not show any sign of toxicity up to oral dose
      of 2g/kg in mice.

PMID- 18639620
TI  - Ficus spp. (fig): ethnobotany and potential as anticancer and anti-inflammatory
      agents.
AB  - This review explores medieval, ancient and modern sources for
      ethnopharmacological uses of Ficus (fig) species, specifically for employment
      against malignant disease and inflammation. The close connection between
      inflammatory/infectious and cancerous diseases is apparent both from the
      medieval/ancient merging of these concepts and the modern pharmacological
      recognition of the initiating and promoting importance of inflammation for cancer
      growth. Also considered are chemical groups and compounds underlying the
      anticancer and anti-inflammatory actions, the relationship of fig wasps and fig
      botany, extraction and storage of fig latex, and traditional methods of preparing
      fig medicaments including fig lye, fig wine and medicinal poultices.

PMID- 18639621
TI  - Antinociceptive activity of Buddleja globosa (matico) in several models of pain.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leaf extracts of Buddleja globosa (Buddlejaceae)
      are used in Chilean folk medicine for wound healing. The anti-inflammatory (topic
      and per os), analgesic (per os) effects and the antioxidant activity of Buddleja
      globosa were for the first time reported by us. AIM OF THE STUDY: Assess the
      antinociceptive activity of the methanol sequential and global extracts using
      complementary chemical and thermal models of pain, characterize pharmacologically
      the antinociception induced, evaluate seasonal influence to support Buddleja
      globosa medicinal use. MATERIALS AND METHODS: Global methanol, sequential
      methanol and ethanol (leaves collected in autumn and summer) extracts were
      evaluated for oral and topic analgesia in tail flick, formalin and writhing
      models, verbascoside and 7-O-luteolin glucoside were assayed in tail flick and
      writhing. Ibuprofen was used as reference. For characterization of induced
      antinociception, naltrexone, naltrindole, tropisetron, nor-binaltorphimine,
      prazosin, yohimbine, atropine, and N-nitro-l-arginine methyl ester were used as
      antagonists and inhibitors drugs. RESULTS: Seasonal influence was observed since
      autumn extract resulted less active. Extracts showed a dose-dependent
      antinociceptive activity in all assays, the highest effects were obtained for the
      formalin and writhing test. Verbascoside was more active than ibuprofen in the
      writhing test (67.6% and 50.0% at equimolar doses) and showed similar effects in
      the tail flick (topic and oral) near 25% at equivalent doses - ED25 or EC25 - to
      ibuprofen. Luteolin 7-O-glucoside was slightly more active in the tail flick test
      and nearly half active than verbascoside in the writhing assay. Effectiveness was
      higher for the sequential than for global alcoholic extracts, and can be
      increased by selective blocking of opioid receptors. Global methanol extract
      seems modulated only by naltrexone. CONCLUSIONS: Analgesic effect of Buddleja
      globosa is here demonstrated validating its use in traditional medicine. Season
      influence is important to be considered.

PMID- 18639622
TI  - Antimicrobial activity of South African Podocarpus species.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Several species of Podocarpus (Podocarpaceae) are
      utilized in treating ailments across the world. In Africa, four species are used
      traditionally in both animal and human health. AIM OF THE STUDY: To investigate
      the antimicrobial activity of Podocarpus species against Bacillus subtilis,
      Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Candida
      albicans. MATERIALS AND METHODS: Six solvents of varying polarity were used for
      extraction. Antibacterial activity was assessed using the microdilution bioassay
      and for antifungal activity, the microdilution bioassay and (M27-P) broth
      dilution were used. RESULTS: All species exhibited antimicrobial activity with
      MIC values of less than 1mg/ml. Inhibition against Gram-positive bacteria was
      stronger with an MIC value of 98 microg/ml while for Gram-negative bacteria, the
      highest inhibition was against Klebsiella pneumoniae with an MIC value of 0.33
      mg/ml. All species exhibited strong antifungal activity with the best MIC being
      30 microg/ml after 48 h. CONCLUSIONS: All four species exhibited strong
      inhibition against all tested microbials, based on Aligiannis et al. [Aligiannis,
      N., Kalpotzakis, E., Mitaku, S., Chinou, I.B., 2001. Composition and
      antimicrobial activity of the essential oils of two Origanum species. Journal of
      Agricultural and Food Chemistry 40, 4168-4170] classification they can be
      classified as strong inhibitors.

PMID- 18639623
TI  - Aging of the prostate epithelial stem/progenitor cell.
AB  - Maintenance of the prostatic epithelial cell compartment is ensured by
      proliferation of adult epithelial progenitor or stem cells. These cells are
      characterized by an undifferentiated state, high proliferative capacity and long
      life span. Prostate progenitor/stem cells are localized in their stem cell-niche
      in the basal cell compartment in close contact to the basement membrane and the
      stromal cell compartment and are characterized by expression of the basal
      cytokeratins 5 and 14, high levels of integrins, CD44, the stem cell markers
      CD133 and ABCG2, and AR negativity. They give rise to secretory luminal
      (cytokeratins 8/18, CD57, AR, p27, PSA, PAP) and neuroendocrine cells
      (cytokeratins 8/18, CD57, CgA, NSE, NEPs), the two major cell types observed in
      the glandular epithelium. A growing body of experimental evidence has identified
      the amplifying progenitor/stem cell (CD44(+), alpha(2)beta(1)(hi), CD133(+)), as
      a putative origin of prostate cancer. Differentiation of this cell type can be
      affected by mutations in the intrinsic genetic program, by age-related changes in
      stromal-epithelial interactions or in the basement membrane/ECM composition. All
      these stochastic events occur during aging and can transform a normal prostate
      progenitor/stem cell into a cancer stem cell, a source of androgen-dependent and
      independent tumor cell clones. Thus, the heterogeneous and multifocal nature of
      prostatic cancer with a pleora of different tumor cell clones clearly reflects
      the differentiation capacity of the prostatic epithelial progenitor cells.

PMID- 18639624
TI  - Reversed micelle solvents as tools of enzyme purification and enzyme-catalyzed
      conversion.
AB  - Reversed micelle solvents represent nanometer-sized aqueous droplets stabilized
      by surfactants inside the bulk organic solvents. The aqueous cores can host
      various hydrophilic solutes, including bioactive substances thus revealing a
      challenge to the biotechnology's needs of the safe media for bioseparations and
      bioconversions. This review discusses the structure and the properties of
      reversed micelle solvents in view of the parameters that can be easily operated
      in technology to achieve safe liquid-liquid extraction of proteins/enzymes or
      bioconversion of hydrophobic substrates. The paper highlights the importance of
      how the reversed micelle microenvironment should be arranged with respect to the
      preservation of the activity of the enzyme as target product or biocatalyst. The
      main aspects are demonstrated with own experimental results on alpha-amylase
      purification and lipase-catalyzed esterification using cationic reversed micelle
      solvents. The trials of performing continuous processes involving reversed
      micellar separation and reaction media are also reviewed and the current problems
      are addressed.

PMID- 18639625
TI  - Induction of apoptosis by streptochlorin isolated from Streptomyces sp. in human
      leukemic U937 cells.
AB  - Streptochlorin is a small molecule that produced by marine Streptomyces sp. that
      is known to have anti-angiogenic and anti-cancer properties. However, the
      mechanism by which streptochlorin functions is not well understood. In this
      study, we investigated the pro-apoptotic effect of streptochlorin in human
      leukemic U937 cells. Streptochlorin treatment resulted in concentration- and time
      dependent growth inhibition by inducing apoptosis. The increase in apoptosis that
      was induced by streptochlorin was correlated with down-regulation of anti
      apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Bax and FasL, a
      decrease in the mitochondrial membrane potential (MMP), activation of caspases
      and degradation of poly-(ADP-ribose)polymerase and phospholipase C-gamma1
      protein. In addition, the cytotoxic effects and apoptotic characteristics induced
      by streptochlorin were significantly inhibited by z-DEVD-fmk, a caspase-3
      inhibitor, which demonstrates the important role that caspase-3 played in the
      process. Furthermore, Bcl-2 overexpression significantly reversed the
      streptochlorin-induced growth inhibitory effects via inhibition of the MMP
      collapse and caspases activation and effectively attenuated the apoptotic
      response to streptochlorin. However, the elevated levels of FasL expression
      induced by streptochlorin were not reduced by Bcl-2 overexpression. Taken
      together, these findings demonstrate that the pro-apoptotic effect of
      streptochlorin is mediated through activation of caspases and mitochondria in
      U937 cells.

PMID- 18639626
TI  - Analysis of sequence variability and protein domain architectures for bovine
      peptidoglycan recognition protein 1 and Toll-like receptors 2 and 6.
AB  - The mammalian Toll-like receptors (TLRs) recognize invading pathogens, thereafter
      provoking innate immune responses, whereas peptidoglycan recognition protein 1
      (PGLYRP1) is directly microbicidal. The primary objective of this study was to
      characterize single-nucleotide polymorphisms (SNPs) and insertion-deletion
      polymorphisms (indels) within bovine TLR2, TLR6, and PGLYRP1, thereby
      facilitating future TLR signaling, association, and PGLYRP1 microbicidal assays
      relevant to bovine innate immunity. Comparative sequence analysis for 10 bovine
      breeds revealed 83 polymorphisms (82 SNPs, 1 indel), with 15 nonsynonymous SNPs
      located within predicted functional domains. Of the 83 polymorphisms detected, 72
      (87%) are reported here for the first time. Several predicted amino acid
      replacements encoded by bovine TLR2 and TLR6, but not PGLYRP1, resulted in the
      confident prediction of protein domain alterations. Prediction and comparison of
      protein domain architectures for TLR2 and TLR6 revealed six regions of leucine
      rich-repeat patterning that was conserved among multiple species. Collectively,
      differences in the patterns and frequencies of polymorphism were noted between
      bovine TLRs that predominantly recognize viral ligands (TLRs 3, 7, 8, 9) and
      those that recognize microbial and/or unknown ligands (TLRs 1, 2, 5, 6, 10).

PMID- 18639628
TI  - Counter-stress effects of relaxation on proinflammatory and anti-inflammatory
      cytokines.
AB  - The counter-stress effects of relaxation on proinflammatory and anti-inflammatory
      cytokines were examined. From 36 medical students, 18 were randomly assigned to
      the relaxation group, and 18 were randomly assigned to the non-relaxation group.
      Relaxation lasted for four weeks. The levels of stimulated production of IL-6,
      TNF-alpha, and IL-10, and blood pressure were measured during the non-examination
      period (baseline period) and the pre-examination period (stress period). The
      levels of perceived stress were assessed by the Global Assessment of Recent
      Stress (GARS) scale, the Stress Response Inventory (SRI) and the Symptom
      Checklist-90-Revised (SCL-90-R) anxiety subscale. Repeat measure ANOVA revealed
      that the SRI total score, scores of the SCL-90-R anxiety subscale and diastolic
      blood pressure were significantly higher during the stress period than during the
      baseline period regardless of groups. The level of IL-6 production was
      significantly lower but the level of IL-10 production was significantly higher
      during the stress period than during the baseline period. Significant reduction
      in the delta (stress period value minus baseline period value) in the total GARS
      score, systolic and diastolic blood pressure, the levels of IL-6 and TNF-alpha
      production but significant enhancement in the delta in the level of the IL-10
      production were found in the relaxation group compared with the non-relaxation
      group. These results suggest that relaxation is associated with reduction in
      stress-induced psychological or physiological responses and proinflammatory
      cytokine alterations but with enhancement in stress-induced anti-inflammatory
      cytokine alteration. Therefore, relaxation is more likely to have counter-stress
      effect on proinflammatory cytokines than on anti-inflammatory cytokine.

PMID- 18639627
TI  - Psychological stress exacerbates primary vaginal herpes simplex virus type 1 (HSV
      1) infection by impairing both innate and adaptive immune responses.
AB  - Chronic psychological stress is generally immunosuppressive and contributes to an
      increase in herpes simplex virus (HSV) pathogenicity. We have previously shown
      that mice experiencing stress at the time of intranasal HSV infection have
      increased levels of infectious virus in their nasal cavity, as compared to
      control mice that were not subjected to stress. We have extended our studies to
      determine the effects of stress at another clinically-relevant mucosal site by
      examining the immune response to and pathogenesis of vaginal HSV infection. Mice
      experiencing psychological stress during vaginal HSV infection exhibited an
      increase in both vaginal viral titers and the pathology associated with this HSV
      infection. We demonstrate that these observations result from the failure of both
      the innate and HSV-specific adaptive immune responses. At 2 days post-infection,
      NK cell numbers were significantly decreased in mice experiencing restraint
      stress. Studies examining the adaptive immune response revealed a decrease in the
      number of HSV-specific CD8(+) T cells in not only the vaginal tissue itself but
      also the draining iliac lymph nodes (ILN). Furthermore, the number of functional
      cells, in terms of both their degranulation and interferon-gamma production, in
      the ILN of stressed mice was decreased as compared to non-stressed mice. We
      conclude that psychological stress, through its suppression of both innate and
      adaptive immune responses, may be an important factor in the ability to control
      vaginal HSV infection.

PMID- 18639629
TI  - Brain acetylcholinesterase activity controls systemic cytokine levels through the
      cholinergic anti-inflammatory pathway.
AB  - The excessive release of cytokines by the immune system contributes importantly
      to the pathogenesis of inflammatory diseases. Recent advances in understanding
      the biology of cytokine toxicity led to the discovery of the "cholinergic anti
      inflammatory pathway," defined as neural signals transmitted via the vagus nerve
      that inhibit cytokine release through a mechanism that requires the alpha7
      subunit-containing nicotinic acetylcholine receptor (alpha7nAChR). Vagus nerve
      regulation of peripheral functions is controlled by brain nuclei and neural
      networks, but despite considerable importance, little is known about the
      molecular basis for central regulation of the vagus nerve-based cholinergic anti
      inflammatory pathway. Here we report that brain acetylcholinesterase activity
      controls systemic and organ specific TNF production during endotoxemia.
      Peripheral administration of the acetylcholinesterase inhibitor galantamine
      significantly reduced serum TNF levels through vagus nerve signaling, and
      protected against lethality during murine endotoxemia. Administration of a
      centrally-acting muscarinic receptor antagonist abolished the suppression of TNF
      by galantamine, indicating that suppressing acetylcholinesterase activity,
      coupled with central muscarinic receptors, controls peripheral cytokine
      responses. Administration of galantamine to alpha7nAChR knockout mice failed to
      suppress TNF levels, indicating that the alpha7nAChR-mediated cholinergic anti
      inflammatory pathway is required for the anti-inflammatory effect of galantamine.
      These findings show that inhibition of brain acetylcholinesterase suppresses
      systemic inflammation through a central muscarinic receptor-mediated and vagal-
      and alpha7nAChR-dependent mechanism. Our data also indicate that a clinically
      used centrally-acting acetylcholinesterase inhibitor can be utilized to suppress
      abnormal inflammation to therapeutic advantage.

PMID- 18639630
TI  - Molecular insights into connective tissue growth factor action in rat pancreatic
      stellate cells.
AB  - Pancreatic fibrosis, a key feature of chronic pancreatitis and pancreatic cancer,
      is mediated by activated pancreatic stellate cells (PSC). Connective tissue
      growth factor (CTGF) has been suggested to play a major role in fibrogenesis by
      enhancing PSC activation after binding to alpha5beta1 integrin. Here, we have
      focussed on molecular determinants of CTGF action. Inhibition of CTGF expression
      in PSC by siRNA was associated with decreased proliferation, while application of
      exogenous CTGF stimulated both cell growth and collagen synthesis. Real-time PCR
      studies revealed that CTGF target genes in PSC not only include mediators of
      matrix remodelling but also the proinflammatory cytokines interleukin (IL)-1beta
      and IL-6. CTGF stimulated binding of NF-kappaB to the IL-6 promoter, and siRNA
      targeting the NF-kappaB subunit RelA interfered with CTGF-induced IL-6
      expression, implicating the NF-kappaB pathway in the mediation of the CTGF
      effect. In further studies, we have analyzed regulation of CTGF expression in
      PSC. Transforming growth factor-beta1, activin A and tumor necrosis factor-alpha
      enhanced expression of the CTGF gene, while interferon-gamma displayed the
      opposite effect. The region from -74 to -125 of the CTGF promoter was revealed to
      be critical for its activity in PSC as well as for the inhibitory effect of
      interferon-gamma. Taken together, our results indicate a tight control of CTGF
      expression in PSC at the transcriptional level. CTGF promotes fibrogenesis both
      directly by enhancing PSC proliferation and matrix protein synthesis, and
      indirectly through the release of proinflammatory cytokines that may accelerate
      the process of chronic inflammation.

PMID- 18639631
TI  - Ferrous iron transport protein B gene (feoB1) plays an accessory role in
      magnetosome formation in Magnetospirillum gryphiswaldense strain MSR-1.
AB  - To investigate the role of ferrous iron transport (Feo) systems in magnetosome
      formation, the gene for protein FeoB (feoB1), encoding 704 amino acids, was
      cloned from magnetotactic bacterium Magnetospirillum gryphiswaldense strain MSR
      1. feoB1 constitutes a putative operon with feoA1, and the interval between the
      two genes is 36 base pairs. A feoB1-deficient mutant (DeltafeoB1) was
      constructed, and compared with wild-type in terms of iron uptake, iron content
      and functional complementation. Ferrous iron and ferric iron uptake in wild-type
      were respectively 1.8-fold and 1.3-fold higher than in the DeltafeoB1 mutant.
      Iron content (w/w) of DeltafeoB1 mutant was enhanced only slightly as
      extracellular iron concentration (either ferrous or ferric citrate) increased,
      whereas iron content of wild-type increased about 2-fold as extracellular iron
      concentration rose from 20 to 80 microM. Transmission electron microscopy
      revealed that DeltafeoB1 cells grown with either ferrous or ferric citrate
      produced fewer magnetosomes, with smaller diameter, compared to wild-type cells.
      Assay of feoAB1 promoter-lacZ transcriptional fusions indicated that the feoAB1
      putative operon was downregulated when MSR-1 cells were grown under iron-rich
      condition. Magnetosome formation was reduced but not abolished in the feoB1
      mutant, indicating that FeoB1 protein plays a significant role in this process.
      Other iron transport systems are presumed to be involved in iron uptake in MSR-1.

PMID- 18639632
TI  - Identification of interspecies difference in efflux transporters of hepatocytes
      from dog, rat, monkey and human.
AB  - The large interspecies differences of hepatobiliary transport present a challenge
      for the allometric prediction of human biliary excretion for drug candidates
      primarily cleared via hepatobiliary secretion. In the present study, we
      determined the metabolic stabilities of common fluorescent substrates of
      hepatobiliary efflux transporters and developed a rapid efflux assay to determine
      the functional activities of MRP/Mrp, BCRP/Bcrp and P-gp in hepatocytes of four
      species. The specificities of transporter-mediated dye efflux were confirmed by
      selective transporter inhibitors. Among tested species, transporter-specific dye
      efflux kinetics was consistent between freshly isolated and cryopreserved
      hepatocytes. Hepatocyte elimination half-lives of MRP/Mrp substrates GS-MF and
      calcein were observed in the rank order of human>monkey>dog>rat. The fourfold
      higher MRP/Mrp substrate efflux rate of rat hepatocytes compared to human is
      likely due to the species-specific functional differences of MRP2/Mrp2 expressed
      on the canalicular membrane. We also observed efficient BCRP-mediated
      pheophorbide A (PhA) efflux by human and dog hepatocytes, while PhA extrusion in
      monkey and rat hepatocytes appeared limited. P-gp function measured by DiOC2(3)
      efflux was minimal in hepatocytes of all origins and no significant species
      differences were detected. Our results demonstrated marked differences in
      hepatocyte MRP/Mrp and BCRP/Bcrp activities across species, indicating that they
      may contribute to the species differences of in vivo hepatobiliary excretion.
      These results also suggest the potential utility of primary hepatocytes, either
      fresh or cryopreserved, as an in vitro model to predict interspecies differences
      in the biliary transport of MRP/Mrp and BCRP/Bcrp substrates.

PMID- 18639633
TI  - The neurobiology of social decision-making.
AB  - Humans live in highly complex social environments and some of our most important
      decisions are made in the context of social interactions. Research that probes
      the neural basis of decision-making in the context of social interactions
      combines behavioral paradigms from game theory with a variety of methods from
      neuroscience. The neural correlates of decision making in reciprocal exchange and
      bargaining games have been probed with functional neuroimaging, transcranial
      magnetic stimulation, and pharmacological manipulations. These studies have begun
      to elucidate a set of brain regions and neurotransmitter systems involved in
      decision-making in social interactions.

PMID- 18639635
TI  - Differentially modulated dendritic cells induce regulatory T cells with different
      characteristics.
AB  - Dexamethason (DEX) treated DC display several features that establish them as
      candidates for specific allogeneic tolerance induction. We report the results of
      in vitro studies of polarization of the alloimmune T cell response with two types
      of differentially modulated human DC. Both DEX treated DC triggered by LPS for 6
      h (DEX6-DC) and DEX treated DC triggered by LPS for 48 h (DEX48-DC) acquired low
      levels of costimulatory, adhesion, and MHC class II molecules compared with
      mature DC (mDC). In contrast to mDC, both DEX6-DC and DEX48-DC did not produce
      any IL-12. DEX6-DC were able to produce significant amounts of IL-10 whereas
      DEX48-DC did not actively produce IL-10. Conversely, the induction of IL-10
      producing cells was significantly increased when PBL were stimulated with DEX48
      DC compared with DEX6-DC. Both stimulation of PBL with DEX6-DC and DEX48-DC led
      to the induction of cell populations able to suppress the proliferative
      alloimmune response of primed T cells in a cell-cell contact independent and
      antigen-nonspecific manner. Tregs obtained after stimulation with DEX48-DC were
      also able to inhibit the IFN-gamma production of the effector cells and this
      effect could be blocked by anti-IL-10. Tregs induced by DEX6-DC produced similar
      amounts of IL-10, yet were not able to inhibit IFN-gamma production of the
      effector T cells, indicating a different mechanism. In summary, we show that
      differential modulation of DC results in the induction of different populations
      of regulatory T cells.

PMID- 18639634
TI  - Human time perception and its illusions.
AB  - Why does a clock sometimes appear stopped? Is it possible to perceive the world
      in slow motion during a car accident? Can action and effect be reversed? Time
      perception is surprisingly prone to measurable distortions and illusions. The
      past few years have introduced remarkable progress in identifying and quantifying
      temporal illusions of duration, temporal order, and simultaneity. For example,
      perceived durations can be distorted by saccades, by an oddball in a sequence, or
      by stimulus complexity or magnitude. Temporal order judgments of actions and
      sensations can be reversed by the exposure to delayed motor consequences, and
      simultaneity judgments can be manipulated by repeated exposure to nonsimultaneous
      stimuli. The confederacy of recently discovered illusions points to the
      underlying neural mechanisms of time perception.

PMID- 18639636
TI  - Tyrosine hydroxylase phosphorylation increases in response to ATP and
      neuropeptide Y co-stimulation of ERK2 phosphorylation.
AB  - ATP and neuropeptide Y (NPY) are examples of agents co-secreted with
      catecholamines from neuronal and neuroendocrine cells which may regulate the
      function of the cells from which they are released. For example, ATP and NPY
      could influence chromaffin cell activity in an autocrine or paracrine manner. The
      primary recognized function of chromaffin cells is the synthesis and secretion of
      catecholamines; therefore, we hypothesize that ATP and NPY can regulate
      catecholamine synthesis in chromaffin cells. ATP increases phosphorylation of
      tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis,
      at Ser31 with a potency similar to that for ERK1/2 phosphorylation, the kinase
      responsible for TH phosphorylation at this site. Moreover, NPY co-stimulation
      increases the potency of ATP for both ERK1/2 and TH phosphorylation, while having
      no effect on these parameters alone. ATP and NPY had no effect on TH
      phosphorylation at Ser40, the primary site responsible for acute activation of
      the enzyme. Correspondingly, ATP and NPY did not increase TH activity.
      Additionally, ATP or ATP and NPY had no effect on TH expression. TH
      phosphorylation at Ser31 may be responsible for stabilization of the enzyme or
      may increase the rate and extent of phosphorylation of Ser40. We propose that ATP
      and NPY may serve to enhance the stimulatory effects of other agents on TH
      activity.

PMID- 18639637
TI  - The immune system and the repair of skeletal muscle.
AB  - Skeletal muscle injury, despite the initial trigger, leads to a stereotypical
      cascade of events mediated by cells of the immune system. Acute damage recruits
      cells of the innate immune system (polymorphonuclear leukocytes and
      monocytes/macrophages) that initially release noxious molecules and clear the
      cellular debris. Macrophages in particular display two distinct differentiation
      patterns. At early times after acute damage inflammatory macrophages are
      predominant, and play a non-redundant role in the clearance of cellular debris.
      At later time points, when fibre regeneration occurs, macrophages acquire a de
      activated phenotype, which has been associated to tissue remodelling. A role for
      cells of the acquired immune system, in particular antigen-specific T and B
      cells, in muscle regeneration has been envisaged, but still needs to be
      elucidated. Similar events possibly play a role during persistent muscle damage
      in which fibres never completely heal. As a consequence infiltrating leukocytes
      stay alive and are continuously activated. Their effector function in situ
      contributes to perpetuate the damage and results in the deposition of collagen
      with interstitial fibrosis and fat accumulation. In this review we will discuss
      the events characterising acute and persistent damage in stretch-induced injury,
      autoimmune polymyositis, inclusion bodies myositis and muscular dystrophies. We
      will focus on the molecular interactions involved in the positive and negative
      regulation of the inflammatory damage, with specific attention to their
      exploitation in the context of strategies to limit muscle wasting and supporting
      fibre regeneration.

PMID- 18639638
TI  - Local RAS and inflammatory factors are involved in cardiovascular hypertrophy in
      spontaneously hypertensive rats.
AB  - The renin-angiotensin system (RAS) and inflammation may play a decisive role in
      hypertensive end organ damage (EOD) including left ventricular (LV) hypertrophy
      and vascular remodeling. It is not clear whether the local RAS and inflammatory
      factors are involved in hypertensive EOD, and which RAS or inflammatory factors
      (systematic or local) is more important in EOD. Hemodynamics, cardiovascular
      hypertrophy, angiotensin II (Ang II) concentration and inflammatory factors in
      spontaneously hypertensive rats (SHR) were measured. mRNA expression of tissue
      RAS and inflammatory factors in SHR was assayed by real-time PCR. The independent
      effects and relative importance of hemodynamic factors and mRNA expression of RAS
      and inflammatory factors in local tissue on cardiovascular hypertrophy were
      assessed by stepwise multivariate regression analysis. It was found that blood
      pressure (BP), blood pressure variability, circulating Ang II, inflammatory
      factors, cardiac and aortic gene expressions of all the components of RAS and
      some inflammatory factors were elevated, and baroreflex sensitivity (BRS) was
      decreased in SHR. Changes of mRNA expressions of RAS components and inflammatory
      factors was unidirectional in the heart and aorta in SHR. It is the tissue RAS,
      rather the circulating RAS and inflammatory factors, that contributed to
      hypertensive cardiovascular hypertrophy. Statistically, LV hypertrophy was mainly
      determined by diastolic blood pressure and the cardiac angiotensin-converting
      enzyme gene expression, and aortic hypertrophy was mainly correlated with
      baroreflex sensitivity.

PMID- 18639639
TI  - Efficient system for biotinylated recombinant Ets-1 production in Escherichia
      coli: a useful tool for studying interactions between Ets-1 and its partners.
AB  - Identification of Ets-1 interaction partners is critical for understanding its
      properties. Ets-1 DNA-binding is governed by an intramolecular mechanism called
      autoinhibition. Ets-1 increases its DNA-binding affinity by counteracting
      autoinhibition through binding either to a particular organization of Ets binding
      sites (EBS) in palindrome, as in the Stromelysin-1 promoter, or to EBS adjacent
      to DNA-binding sites of its partners by combinatorial interactions, as in the
      Collagenase-1 promoter. Identification of new Ets-1 interaction partners should
      allow the identification of new functions for this transcription factor. To this
      end, we fused a biotin tag to Ets-1 protein in order to copurify it and its
      partners by affinity. For the first time, we cloned, produced in Escherichia coli
      and purified a biotinylated recombinant Ets-1 protein using the T7-Impact system
      (New England Biolabs), adapted to induce biotinylation. Nearly 100% biotinylation
      was attained without altering Ets-1 properties. Biotinylated Ets-1 bound to and
      transactivated the Stromelysin-1 promoter the same way as native Ets-1 did. It
      also conserved interactions with known Ets-1 partners such as c-Jun, Erk-2 and
      Runx-1. In addition, streptavidin pull-down and surface plasmon resonance assays
      demonstrated that biotinylated Ets-1 is a useful tool for qualitative and
      quantitative studies of Ets-1 interaction with its partners.

PMID- 18639640
TI  - Heterologous protein production in Escherichia coli using the propionate
      inducible pPro system by conventional and auto-induction methods.
AB  - We examined expression of two plant genes encoding coclaurine N-methyltransferase
      (CMT) and norcoclaurine synthase (NCS) in Escherichia coli from the Salmonella
      entericaprpBCDE promoter (P(prpB)) and compared it to that from the strongest
      IPTG-inducible promoter, P(T7). In contrast to our previous study showing
      slightly higher production of green fluorescent protein (GFP) from the pPro
      system compared to that from the T7 system, production of two plant proteins CMT
      and NCS from P(prpB) was 2- to 4-fold higher than that from P(T7). Unlike P(T7),
      expression from P(prpB) did not reduce cell growth even when highly induced,
      indicating that this propionate-inducible system is more efficient for
      overproduction of proteins that result in growth inhibition. In an auto-induction
      experiment, which does not require monitoring the culture or adding inducer
      during cell growth, the pPro system exhibited much higher protein production than
      the T7 system. These results strongly indicate that the pPro system is well
      suited for overproduction of recombinant proteins.

PMID- 18639641
TI  - Electromagnetic source reconstruction for group studies.
AB  - The aim of this paper is to describe a simple procedure for electromagnetic (EEG
      or MEG) source reconstruction, in the context of group studies. This entails a
      simple extension of existing source reconstruction techniques based upon the
      inversion of hierarchical models. The extension ensures that evoked or induced
      responses are reconstructed in the same subset of sources, over subjects.
      Effectively, the procedure aligns the deployment of reconstructed activity over
      subjects and increases, substantially, the detection of differences between
      evoked or induced responses at the group or between-subject level.

PMID- 18639642
TI  - Systematics of Zoothera thrushes, and a synthesis of true thrush molecular
      systematic relationships.

PMID- 18639644
TI  - The effects of dietary fatty acids on liver fatty acid composition and Delta(6)
      desaturase expression differ with ambient salinities in Siganus canaliculatus.
AB  - Delta(6)-Desaturase (linoleoyl-CoA desaturase, EC 1.14.19.3) is the rate-limiting
      enzyme in the biosynthetic pathway of highly unsaturated fatty acid (HUFA). In
      this report, a Delta6 desaturase-like cDNA was cloned, and the relation of HUFA
      biosynthetic activity in liver with ambient salinity as well as dietary fatty
      acids was investigated in the euryhaline teleost Siganus canaliculatus. After the
      juveniles were fed four formulated diets (D1-D4) with different essential fatty
      acid composition (D1 with 23.49% HUFA, D2-D4 were HUFA-free, linoleic and alpha
      linolenic acids account for 21.1% and 0.38%, 13.99% and 11.64%, 18.31% and 5.82%
      of the total fatty acids, respectively) for nine weeks, the growth performance
      showed no difference among groups in brackish water (10 ppt) or seawater (32 ppt)
      (P>0.05). Comparing liver fatty acids with fish fed D1, the content of
      arachidonic acid in fish fed D2 or D4 was significantly higher in 10 ppt
      (P<0.05), but showed no difference in 32 ppt; the contents of eicosapentaenoic
      (EPA), docosapentaenoic (DPA) and docosahexaenoic (DHA) acids in 10 ppt, as well
      as EPA in 32 ppt in fish fed D3 showed no difference, whereas those of DPA and
      DHA were significantly lower in 32 ppt (P<0.05). These data suggest that S.
      canaliculatus may convert linoleic and alpha-linolenic acids into HUFA and such a
      capacity was stronger in low salinity than that in high salinity. Consistent with
      this, the liver levels of Delta6 desaturase mRNA in fish fed D2-D4 were generally
      higher than in fish fed D1 in both salinities, and the total expression level in
      10 ppt was about 1.56 times of that in 32 ppt, suggesting that transcriptional
      control of Delta6 desaturase is involved in such a HUFA biosynthesis. To our
      knowledge, this is the first report showing the relation of HUFA biosynthetic
      activity with ambient salinity in a euryhaline fish.

PMID- 18639643
TI  - Effects of imaging conditions on mitochondrial transport and length in larval
      motor axons of Drosophila.
AB  - The distribution of mitochondria is sensitive to physiological stresses and
      changes in metabolic demands. Consequently, it is important to carefully define
      the conditions facilitating live imaging of mitochondrial transport in dissected
      animal preparations. In this study, we examined Schneider's and the haemolymph
      like solutions HL3 and HL6 for their suitability to image mitochondrial transport
      in motor axons of dissected Drosophila melanogaster larvae. Overall,
      mitochondrial transport kinetics in larval motor axons appeared similar among all
      three solutions. Unexpectedly, HL3 solution selectively increased the length of
      mitochondria in the context of the net-direction of transport. We also found that
      mitochondrial transport is sensitive to the extracellular Ca(2+) but not
      glutamate concentration. High concentrations of extracellular glutamate affected
      only the ratio between motile and stationary mitochondria. Our study offers a
      valuable overview of mitochondrial transport kinetics in larval motor axons of
      Drosophila under various conditions, guiding future studies genetically
      dissecting mechanisms of mitochondrial transport.

PMID- 18639645
TI  - Two-domain arginine kinase from the deep-sea clam Calyptogena kaikoi--evidence of
      two active domains.
AB  - The cDNA and deduced amino acid sequences for arginine kinase (AK) from the deep
      sea clam Calyptogena kaikoi have been determined revealing an unusual two-domain
      (2D) structure with molecular mass of 80 kDa, twice that of normal AK. The amino
      acid sequences of both domains contain most of the residues thought to be
      required for substrate binding found in the horseshoe crab Limulus polyphemus AK,
      a well studied system for which several X-ray crystal structures exist. However,
      two highly conserved residues, D62 and R193, that form a salt bridge thereby
      stabilizing the substrate-bound structure have been replaced by G and N in domain
      1, and G and P in domain 2, respectively. The present effort probes whether both
      domains of Calyptogena AK are catalytically competent. Recombinant constructs of
      the wild-type enzyme of both single domains, and of selected mutants of the
      Calyptogena AK have been expressed as fusion proteins with the maltose-binding
      protein. The wild-type two-domain enzyme (2D[WT]) had high AK activity (k(cat)=23
      s(- 1), average value of the two domains), and the single domain 2 (D2[WT])
      showed 1.5-times higher activity (k(cat)=38 s(- 1)) than the wild-type 2D[WT].
      Interestingly, the single domain 1 (D1[WT]) showed only a very low activity
      (k(cat) approximately 0.016 s(- 1)). Introduction of a Y68A mutation in both
      domains virtually abolished catalytic activity. On the other hand, significant
      residual activity was observed (k(cat)=2.8 s(- 1)), when the Y68A mutation was
      introduced only into domain 2 of the two-domain enzyme. A similar mutation in
      domain 1 of the two-domain enzyme reduced activity to a much lower extent
      (k(cat)=11.1 s(- 1)). Although the domains of this "contiguous" dimeric AK each
      have catalytic capabilities, the presence of domain 2 strongly influences the
      stability and activity of domain 1.

PMID- 18639646
TI  - Progress in the evaluation of CDK inhibitors as anti-tumor agents.
AB  - The increase in understanding of the events of cell growth and division has
      enabled the development of pharmacological agents inhibiting key regulatory
      proteins, with the cyclin dependent kinases (CDKs) representing a major area of
      interest. Owing to multiple CDK variants having cell cycle and transcriptional
      regulatory roles and difficulties in generating selective inhibitors, the
      prospects for drug discovery and development are complex. Numerous CDK inhibitors
      with differing mechanistic profiles are currently being preclinically and
      clinically evaluated but have not as of yet resulted in a drug approval. The
      major issues of CDK inhibition related to current understanding from genetic
      studies and also from observed anti-tumor efficacy of representative compounds
      are discussed in this review.

PMID- 18639647
TI  - Antivirulence as a new antibacterial approach for chemotherapy.
AB  - Bacterial resistance to antibiotics is an issue that has led to the search for
      new antibacterial approaches. Drugs targeting virulence is an alternative
      approach to treat infections due to resistant bacteria. There is extensive
      literature and knowledge in the field of bacterial pathogenesis and genomic
      determinant of virulence. As therapeutic targets, virulence factors have been
      primarily addressed in the vaccine field to prevent infection by specific
      pathogens. Recently novel strategies to identify virulence inhibitors have been
      numerous and several new compounds were recently reported. This review emphasizes
      the new virulence inhibitors that have shown a biological activity and have made
      a proof of concept that disarming bacteria lead to the inhibition of bacterial
      infection in experimental models in vivo. Moreover, some of these new
      antivirulence compounds are able to inhibit the virulence of different related
      pathogenic species, indicating that it is possible to target common virulence
      mechanisms. The progress reported recently with proof of concept for
      antivirulence molecules at the preclinical stages should allow the antivirulence
      concept to become a reality as a new antibacterial approach.

PMID- 18639648
TI  - P53 transcriptional activities: a general overview and some thoughts.
AB  - P53 is a master transcriptional regulator controlling several main cellular
      pathways. Its role is to adapt gene expression programs in order to maintain
      cellular homeostasis and genome integrity in response to stresses. P53 is found
      mutated in about half of human cancers and most mutations are clustered within
      the DNA-binding domain of the protein resulting in altered p53 transcriptional
      activity. This illustrates the importance of the gene regulations achieved by
      p53. The aim of this review is to provide a global overview of the current
      understanding of p53 transcriptional activities and to discuss some ongoing
      questions and unresolved points about p53 transcriptional activity.